PMID- 16593707
TI  - Electrical coupling between bipolar cells in carp retina.
AB  - Intracellular recordings were made simultaneously from pairs of neighboring
      bipolar cells by advancing two independent microelectrodes into retinas of carp
      (Cyprinus carpio). Bipolar cells were identified by their response properties and
      in several samples were verified by intracellular injection of Lucifer yellow.
      Current of either polarity injected into one member of the bipolar cell pair
      elicited a signconserving, sustained potential change in the other bipolar cell
      without any significant delay. This electrical coupling was reciprocal, and it
      was observed between cell types similar in function and in morphology. Our
      results strongly suggest that there is a spatial summation of signals at the
      level of bipolar cells, which makes central receptive field areas much larger
      than their dendritic fields.

PMID- 16593708
TI  - Osteoclasts can be induced in fish having an acellular bony skeleton.
AB  - Kelp bass (Paralabrax clathratus) and leopard sharks (Triakis semifasciata) are
      characterized by an acellular (anosteocytic) bony skeleton and a focally
      calcified cartilaginous endoskeleton, respectively. These skeletal forms are not
      considered to function as mineral reservoirs. Previous studies showed that
      implanted bone particles are resorbed in rats by large multinucleated cells with
      ultrastructural features (ruffled borders) characteristic of osteoclasts. We
      tested the ability of fish to resorb bone matrix and to adapt to reduced salinity
      conditions. Bone particles were implanted in sharks and bass maintained in
      seawater (34 ppt, 40.5 mg of calcium per dl) or in diluted seawater (26 ppt, 28.5
      mg of calcium per dl). Sera and elicited tissues were harvested 4 weeks later. In
      sharks, bone particles were not resorbed, and multinucleated cells were not
      evident under either normal or hyposalinity conditions. Shark sera were
      isoosmolar with the seawater or diluted seawater, with serum chemistries of the
      hyposalinity group reflecting the 23% reduction in environmental minerals and
      electrolytes, compared to sharks in normal seawater. In marked contrast, bass
      adapted to diluted seawater resorbed bone particles and maintained normal serum
      chemistries. Electron microcopy showed that the bone particles were surrounded by
      large, foamy multinucleated cells, many with membrane specializations typical of
      osteoclasts from higher vertebrates, i.e., extensive clear zones apposed to
      intact bone matrix and active ruffled borders overlying areas of matrix
      undergoing dissolution. Although osteoclasts had not been described in these
      fish, this study shows that bass have stem cells that can be stimulated to
      differentiate into bone-resorbing osteoclasts.

PMID- 16593710
TI  - Electron-transport-driven proton pumps display nonhyperbolic kinetics: Simulation
      of the steady-state kinetics of cytochrome c oxidase.
AB  - A reaction cycle for electron-transportdriven proton pumps is proposed. It
      includes two distinct conformational states of the pump protein in which the
      primary electron acceptor has different reduction potentials. This has as an
      unavoidable consequence that the steady-state rate equation for the catalytic
      reaction driving the pump is nonhyperbolic. The model can be used to simulate
      experimental results for the kinetics of cytochrome oxidase (EC 1.9.3.1) in a
      wide range of experimental conditions (ionic strength, pH, temperature). It is
      thus not necessary to invoke more than one binding site for cytochrome c to
      account for the biphasic response of the oxidase activity to the concentration of
      this substrate.

PMID- 16593709
TI  - Cloning of cDNA for the contact site A glycoprotein of Dictyostelium discoideum.
AB  - A cell surface glycoprotein of Dictyostelium discoideum with M(r) 80,000 (gp80)
      has been shown to mediate the formation of the developmentally acquired EDTA
      resistant cell-cell binding sites termed contact sites A. We have isolated cDNA
      clones encoding gp80 by immunological screening of an expression library prepared
      in Escherichia coli. Double-stranded cDNA was prepared from poly(A)(+) RNA
      isolated from cells at 8 hr of development and cloned into the bacteriophage
      expression vector lambdagt11. Two recombinant phages containing cDNA inserts of
      1.2 and 0.8 kilobases were isolated and shown to contain sequences coding for
      gp80 by the immunoselect assay. Partial DNA sequence analysis also confirmed that
      one of these cDNA clones, lambdaDdgp80c-19, contained the coding sequence for the
      amino terminus of gp80. DNA-RNA hybridization showed that the insert of
      lambdaDdgp80c-19 hybridized to a single mRNA transcript of approximately 2.0
      kilobases. gp80 mRNA became detectable after 6 hr of development, reached its
      maximum level at 9 hr, and dropped to a negligible level by 15 hr. This pattern
      of mRNA accumulation corresponded closely to that of gp80 synthesis in D.
      discoideum cells, suggesting that gp80 expression is regulated at the
      transcriptional level.

PMID- 16593711
TI  - Light quality regulates expression of chloroplast genes and assembly of
      photosynthetic membrane complexes.
AB  - The concentrations of photosystem I (PSI) and photosystem II (PSII) reaction
      centers and the level of chloroplast reaction center gene transcripts were
      determined in pea plants grown under different light-quality regimes. In plants
      grown in light primarily absorbed by PSI ("red" light), the PSII/PSI reaction
      center ratio was 2-fold greater than that in plants grown in PSII-sensitizing
      ("yellow") light. In addition, the ratio of a PSII gene (psbB) transcript to a
      PSI gene (psaA) transcript was 2.6 times greater in red-grown plants relative to
      yellow-grown plants. Thus, a differential reaction-center concentration in the
      thylakoid membrane was accompanied by a differential expression of reaction
      center genes, suggesting that the synthesis of chloroplast membrane complexes and
      the assembly of photosystems are regulated by light quality at the
      transcriptional and/or post-transcriptional level.

PMID- 16593712
TI  - Mitochondrial DNA differentiation in North Atlantic eels: Population genetic
      consequences of an unusual life history pattern.
AB  - A survey of restriction site polymorphism in the mitochondrial DNA (mtDNA) of the
      American eel Anguilla rostrata showed no genetic divergence among samples from a
      4000-km stretch of North America coastline. Lack of geographic differentiation in
      mtDNA over such a large area contrasts sharply with results for terrestrial and
      freshwater vertebrates and is most likely attributable to the extraordinary life
      history of these catadromous fishes, which involves perhaps a single spawning
      population in the western tropical mid-Atlantic Ocean and subsequent widespread
      dispersal of larvae by ocean currents. However, samples of the European eel
      (nominally Anguilla anguilla) are highly distinct from A. rostrata in mtDNA
      genotype (distinguishable by 11 of 14 restriction endonucleases), contradicting
      some previous suggestions that the two forms belong to the same panmictic
      population. Results of this study emphasize the importance of life history in
      shaping population genetic structure.

PMID- 16593713
TI  - Genetic evidence suggests that homosporous ferns with high chromosome numbers are
      diploid.
AB  - Homosporous ferns have usually been considered highly polyploid because they have
      high chromosome numbers (average n = 57.05). In angiosperms, species with
      chromosome numbers higher than n = 14 generally have more isozymes than those
      with lower numbers, consistent with their polyploidy. By extrapolation,
      homosporous ferns would be expected to have many isozymes. However, ongoing
      surveys indicate that within fern genera, species having the lowest chromosome
      numbers have the number of isozymes considered typical of diploid seed plants.
      Only species above these lowest numbers have additional isozymes. Therefore,
      homosporous ferns either have gone through repeated cycles of polyploidy and gene
      silencing or were initiated with relatively high chromosome numbers. The latter
      possibility represents a radical departure from currently advocated hypotheses of
      fern evolution and suggests that there may be fundamental differences between the
      genomes of homosporous ferns and those of higher plants. These hypotheses can be
      tested by genetic, karyological, and molecular techniques.

PMID- 16593714
TI  - Rhizobium meliloti genes required for nodule development are related to
      chromosomal virulence genes in Agrobacterium tumefaciens.
AB  - Symbiotically essential genes have been identified in Rhizobium meliloti that are
      structurally and functionally related to chromosomal virulence (chv) genes of
      Agrobacterium tumefaciens. Homologous sequences also exist in the genomes of
      other fast-growing rhizobia including Rhizobium trifolii, Rhizobium
      leguminosarum, and Rhizobium phaseoli. In Agrobacterium, the chvA and chvB loci
      are known to be essential for oncogenic transformation of dicotyledonous plants
      and for attachment to plant cells [Douglas, C. J., Staneloni, R. J., Rubin, R. A.
      & Nester, E. W. (1985) J. Bacteriol. 64, 102-106], and the chvB locus has been
      implicated in the production of (1-->2)-beta-glucan, a unique exopolysaccharide
      component [Puvanesarajah, V., Schell, F. M., Stacey, G., Douglas, C. J. & Nester,
      E. W. (1985) J. Bacteriol. 164, 102-106]. Site-directed transposon insertion
      mutants in the chvA and chvB-equivalent regions of R. meliloti are symbiotically
      defective. Mutants in the chvB-equivalent region have been examined in detail and
      have been found to induce the formation of nodule-like structures on alfalfa that
      are devoid of bacteroids, lack infection threads, and cannot fix nitrogen. Such
      mutants fluoresce normally in the presence of Calcofluor, a histochemical stain
      for beta-linked polysaccharides, and produce normal amounts of total
      exopolysaccharide. The Rhizobium loci have been designated ndv because of their
      requirement for nodule development.

PMID- 16593716
TI  - Rapid assay of foreign gene expression in leaf discs transformed by Agrobacterium
      tumefaciens: Role of T-DNA borders in the transfer process.
AB  - We have developed a sensitive leaf disc transformation procedure for studying
      early and/or transient T-DNA expression during Agrobacterium tumefaciens-mediated
      transformation of plant cells. Using this system, we have examined the function
      of T-DNA border sequences on the early expression of T-DNA genes and on the
      stable integration of those genes in infected cells. Deletion of the right border
      from the T-DNA appears to permit transfer of T-DNA genes from the tumor-inducing
      (Ti) plasmid but greatly reduces the frequency of their stable integration. A
      binary vector has been constructed to permit examination of T-DNA border function
      in trans to the Ti plasmid. In this situation, a single T-DNA border is necessary
      for early expression of T-DNA genes and is sufficient for stable integration in
      any orientation.

PMID- 16593715
TI  - Single amino acid substitutions in the enzyme acetolactate synthase confer
      resistance to the herbicide sulfometuron methyl.
AB  - Sulfometuron methyl, a sulfonylurea herbicide, blocks growth of bacteria, yeast,
      and higher plants by inhibition of acetolactate synthase (EC 4.1.3.18), the first
      common enzyme in the biosynthesis of branched-chain amino acids. Spontaneous
      mutations that confer increased resistance to the herbicide were obtained in
      cloned genes for acetolactate synthase from Escherichia coli and Saccharomyces
      cerevisiae. The DNA sequence of a bacterial mutant gene and a yeast mutant gene
      revealed single nucleotide differences from their respective wild-type genes. The
      mutations result in single amino acid substitutions in the structurally
      homologous aminoterminal regions of the two proteins, but at different positions.
      The bacterial mutation results in reduced levels of acetolactate synthase
      activity, reduced sensitivity to sulfometuron methyl, and unaltered resistance to
      feedback inhibition by valine. The yeast mutation results in unaltered levels of
      acetolactate synthase activity, greatly reduced sensitivity to sulfometuron
      methyl, and slightly reduced sensitivity to valine.

PMID- 16593717
TI  - Conductive polymers derived from iron, ruthenium, and osmium metalloporphyrins:
      The shish-kebab approach.
AB  - The synthesis and characterization of pyrazine-bridged polymers of iron(II/III),
      ruthenium(II/III), and osmium(II/III) octaethylporphyrin (dubbed "shish-kebab"
      polymers) are presented. Optical and dc conductivity measurements reveal that the
      ruthenium and osmium polymers, when partially oxidized, are highly conductive.
      Electrochemical and ESR results are presented that indicate the existence of an
      interesting metal-centered conduction pathway. Unlike most of the previously
      reported porphyrinic molecular metals in which the conduction electrons are
      macrocyclic-based, electron transport in these materials proceeds exclusively
      along the metal-pyrazine backbone.

PMID- 16593718
TI  - epsilon factor of representations of classical groups.
AB  - We let G be the isometry group of a nondegenerate symmetric or skew-symmetric
      form h on a space V over some local or global field K [i.e., G = U(V, h)]. We let
      (L)G be the L group of G(o) = the identity component of G and r be the natural
      representation of this group. We develop here a theory of L functions and epsilon
      factors attached to this r. In particular we develop a theory of local and global
      zeta integrals for such G. We use very special intertwining operators; therein we
      require an analysis of the proper normalization of such operators. With such
      techniques we determine the correct epsilon factors associated to local
      representations. The issue of the correct local L factor is discussed.

PMID- 16593720
TI  - Mammary number and litter size in Rodentia: The "one-half rule".
AB  - Litter size and mammary number in the mammalian order Rodentia show a significant
      positive correlation. Mean litter size is typically one-half the number of
      available mammaries, while maximum litter size approximates mammary number.
      Similar relationships are found in the families Muridae, Cricetidae, and
      Sciuridae. The relationship of litter size to mammary number is significantly
      different between the arboreal and terrestrial squirrels, and between the
      hystricomorph and nonhystricomorph rodents. Mammary number may have operated as a
      selective constraint on litter size over evolutionary time.

PMID- 16593719
TI  - Metabolic cooperation following fusion of starfish ootid and primary oocyte
      restores meiotic-phase-promoting activity.
AB  - In the starfish Marthasterias glacialis, polyethylene glycol (PEG) homologous
      fused pairs consisting of two immature oocytes, blocked at the germinal vesicle
      stage, or two ootids, blocked at the female pronucleus stage, remain arrested at
      these specific stages, unless they are stimulated by the hormone 1-methyladenine.
      In contrast, heterologous pairs develop up to female pronucleus formation in the
      immature partner, indicating that maturation-promoting factor was formed under
      these conditions. Kinetics for this process, reconstitution of the nuclear
      envelopes after first polar body extrusion, and delaying effect of emetine argue
      for the existence of a true metabolic cooperation process requiring complementary
      factors present in each partner. The effect of inhibitors that penetrate the
      plasma membrane points to the possible involvement of endogenous proteases that
      may activate latent or neosynthesized maturation-promoting factor precursor
      and/or protein kinases.

PMID- 16593721
TI  - Rapid evolution of a life history trait.
AB  - The copepod Diaptomus sanguineus begins diapause in permanent ponds in late March
      as an adaptation to avoid summer fish predation. During a study of copepod
      populations in two Rhode Island ponds, a severe drought dried one pond killing
      all fish. The second (control) pond did not dry, and no fish were killed. Before
      the drought copepods in the two ponds entered diapause on nearly the same date.
      After the drought, the timing of diapause shifted to later in the year in the
      pond that had lost its fish, while no shift occurred in the control pond. The
      direction of this shift in the onset of diapause is that expected had the
      copepods been released from natural selection for early spring diapause imposed
      by summer fish predation.

PMID- 16593722
TI  - Transposition of the maize controlling element "Activator" in tobacco.
AB  - Transposition of the maize autonomous controlling element Activator (Ac) and a
      nonautonomous derivative, Dissociation (Ds), was investigated in tobacco cells.
      Tobacco protoplasts were transformed with Ti-plasmid vectors that contained Ac or
      Ds flanked by short maize wx gene sequences. The structures of the elements and
      surrounding wx and T-DNA sequences were investigated in nine Ac and five Ds
      tobacco transformants by digestion with restriction enzymes, Southern blotting,
      and hybridization using specific probes. In four of the nine Ac transformed
      lines, Ac had excised from its original position in the T-DNA and inserted at new
      sites in the tobacco genome. Ds did not excise from its original T-DNA position
      in any of the transformants examined. Two Ac fragments and cellular flanking
      sequences were cloned from a line of tobacco in which Ac had transposed.
      Fragments, comprised of sequences flanking the newly integrated Ac elements, were
      used as hybridization probes to normal tobacco DNA and to the tobacco DNA from
      which they were isolated. The Ac copies were integrated into repetitive tobacco
      DNA sequences. Two tobacco fragments containing empty Wx donor sites were cloned
      from the DNA of the same Ac transformant and sequenced. Both sequences are among
      the types of excision products observed to result from Ac-catalyzed excision
      events in maize. Our results indicate that the maize controlling element Ac is
      capable of self-catalyzed transposition in tobacco.

PMID- 16593723
TI  - Efficient cloning of genes of Neurospora crassa.
AB  - We have constructed a genomic library of Neurospora crassa DNA in a cosmid vector
      that contains the dominant selectable marker for benomyl resistance. The library
      is arranged to permit the rapid cloning of Neurospora genes by either sib
      selection or colony-hybridization protocols. Detailed procedures for the uses of
      the library are described. By use of these procedures, a modest number of
      unrelated genes have been isolated. The cloning of trp-3, the structural gene for
      the multifunctional enzyme tryptophan synthetase (tryptophan synthase, EC
      4.2.1.20), is reported in detail; its identity was verified by restriction
      fragment length polymorphism mapping. The strategies described in this paper
      should be of use in the cloning of any gene of Neurospora, as well as genes of
      other lower eukaryotes.

PMID- 16593724
TI  - N-Succinylated intermediates in an arginine catabolic pathway of Pseudomonas
      aeruginosa.
AB  - Arginine-nonutilizing (aru) mutants of Pseudomonas aeruginosa strain PAO
      converted L-arginine to N(2)-succinylarginine or N-succinylglutamate, which were
      identified by high-voltage electrophoresis and HPLC. Addition of aminooxyacetate,
      an inhibitor of pyridoxal phosphate-dependent enzymes, to resting cells of the
      wild-type PAO1 in arginine medium led to the accumulation of N(2)
      succinylornithine. Enzyme assays with crude P. aeruginosa extracts established
      the following pathway: L-arginine + succinyl-CoA --> N(2)-succinylarginine -->
      N(2)-succinylornithine --> N_succinylglutamate 5-semialdehyde --> N
      succinylglutamate --> succinate + glutamate. Succinyl-CoA may be regenerated from
      glutamate via 2-ketoglutarate. L-Arginine induced the enzymes of the pathway, and
      succinate caused catabolite repression. Purified N(2)-acetylornithine 5
      aminotransferase (N(2)-acetyl-L-ornithine: 2-oxoglutarate aminotransferase, EC
      2.6.1.11), an arginine biosynthetic enzyme, efficiently transaminated N(2)
      succinylornithine; this explains the enzyme's dual role in arginine biosynthesis
      and catabolism. The succinylarginine pathway enables P. aeruginosa to utilize
      arginine efficiently as a carbon source under aerobic conditions, whereas the
      other three arginine catabolic pathways previously established in P. aeruginosa
      fulfill different functions.

PMID- 16593725
TI  - Flow-induced anisotropy in the susceptibility of a particle suspension.
AB  - The initial susceptibility, or low-field high-frequency permeability, of a rod
      like particle suspension or polymer solution can become anisotropic when the
      particles or molecules interact with a magnetic field in a directional manner and
      are nonrandomly oriented by certain types of flow field. This is the alignment
      that leads to thixotropy and deviatoric stresses during rheological measurements
      on these fluids. A general expression for the particle order parameter and the
      fluid permeability in terms of Legendre polynomials is derived by calculating the
      ensemble average over all possible orientation angles. This is an integral
      containing the orientation angle-dependent orientation probability function. The
      example case of single-domain magnetic particles suspended in extensional flow of
      a newtonian fluid is examined by using the following well-known models: chain-of
      spheres model for the magnetic properties of a particle and the Kirkwood-Auer
      theory for the orientation probability function. From this, the particle
      orientation in the flow direction downstream from a sharp circular convergence is
      predicted to dramatically increase with an increase in the ratio of the extension
      rate to the particle rotary diffusion coefficient. Consequently, the measured
      permeability of the fluid is predicted to decrease parallel to, and to increase
      perpendicular to, the flow direction.

PMID- 16593726
TI  - Detection and sequence of plus-strand leader RNA of sonchus yellow net virus, a
      plant rhabdovirus.
AB  - Tobacco infected with the plant rhabdovirus sonchus yellow net virus (SYNV)
      contains short, 139- to 144-nucleotide (nt) transcripts complementary to the 3'
      terminus of the negative-strand genomic RNA. These transcripts are similar to the
      leader RNAs associated with several animal rhabdovirus infections in that they
      are encoded by the same region of the genome, but the SYNV transcripts are nearly
      3 times longer than the animal rhabdovirus leader RNAs. The SYNV leader RNAs
      differ markedly in sequence from the leader RNAs associated with strains of
      vesicular stomatitis virus and rabies virus, although the first 30 nt of all
      three transcripts are rich in adenylate residues. The nucleotide sequence
      determined directly from SYNV RNA and from recombinant DNA clones derived from
      SYNV RNA reveals a possible initiation site for transcription of the N-protein
      mRNA that is located 147 nt from the 3' end of genomic RNA. The sequence (UUGU)
      at this site is complementary to the first 4 nt of the N-protein mRNAs of animal
      rhabdoviruses. In SYNV, the first AUG codon in the putative N-protein mRNA is
      located 57 nt downstream (at positions 203-205 in the viral genome) and is
      followed by an open reading frame for the remainder of the 1020 nt determined in
      these experiments.

PMID- 16593727
TI  - In vitro transcription of infectious RNAs from full-length cDNAs of tobacco
      mosaic virus.
AB  - We have cloned full-length double-stranded cDNAs of tobacco mosaic virus (TMV)
      (tomato strain L) RNA into a transcription vector, pPM1, which facilitates the
      correct transcription initiation from the first nucleotide of the inserted double
      stranded cDNA, corresponding to the 5' end of TMV RNA. When plasmid DNA is
      linearized at a unique restriction site (Mlu I) introduced just downstream of the
      double-stranded cDNA insert and used as a template for in vitro transcription by
      Escherichia coli RNA polymerase in the presence of m(7)GpppG, the transcribed
      RNAs are infectious for tobacco plants. A simple reconstitution procedure
      increases the infectivity >100 times. Unexpectedly, both the uncapped transcript
      and the transcript from the uncut plasmid DNA are also infectious, although their
      infectivities are very low. The progeny viruses multiplying in tobacco plants
      accurately reflect the cloned sequence. By the same method, we succeeded in the
      in vitro transcription of infectious RNA of attenuated strain L(11)A, which is
      phenotypically distinguishable from wild-type TMV on both tobacco and tomato
      plants.

PMID- 16593728
TI  - Femtosecond spectroscopy of excitation energy transfer and initial charge
      separation in the reaction center of the photosynthetic bacterium
      Rhodopseudomonas viridis.
AB  - Reaction centers from the photosynthetic bacterium Rhodopseudomonas viridis have
      been excited within the near-infrared absorption bands of the dimeric primary
      donor (P), of the "accessory" bacteriochlorophylls (B), and of the
      bacteriopheophytins (H) by using laser pulses of 150-fsec duration. The transfer
      of excitation energy between H, B, and P occurs in slightly less than 100 fsec
      and leads to the ultrafast formation of an excited state of P. This state is
      characterized by a broad absorption spectrum and exhibits stimulated emission. It
      decays in 2.8 +/- 0.2 psec with the simultaneous oxidation of the primary donor
      and reduction of the bacteriopheophytin acceptor, which have been monitored at
      545, 675, 815, 830, and 1310 nm. Although a transient bleaching relaxing in 400
      +/- 100 fsec is specifically observed upon excitation and observation in the 830
      nm absorption band, we have found no indication that an accessory
      bacteriochlorophyll is involved as a resolvable intermediary acceptor in the
      primary electron transfer process.

PMID- 16593729
TI  - Isolation and characterization of the actin gene from Tetrahymena thermophila.
AB  - The macronucleus of Tetrahymena thermophila contains a single actin gene. We have
      isolated this gene from a partial plasmid library by using the yeast actin gene
      as a probe. The nucleotide sequence of the gene has been determined and the amino
      acid sequence of the potential protein deduced. The encoded protein is 375 amino
      acids long, one amino acid longer than the yeast actin. It is one of the most
      divergent actins sequenced to date, being only 75% homologous to yeast actin.
      Unlike the actin genes from most other organisms, it does not contain introns.
      The coding region contains TAA and TAG codons; the translation termination codon
      is TGA. Comparison of the amino acid sequence of the Tetrahymena actin with that
      of actins from other organisms suggests that TAG may code for glutamic acid. The
      gene is transcribed from multiple initiation sites between 57 and 98 nucleotides
      upstream of the translation start codon. The 5' flanking region is very A+T-rich
      and contains numerous "TATA-like" sequences upstream of the transcription start
      sites.

PMID- 16593730
TI  - Autonomously replicating RNA in mitochondria of maize plants with S-type
      cytoplasm.
AB  - Mitochondria isolated from maize plants with S-type male-sterile cytoplasms are
      capable of synthesizing four species of RNA at concentrations of actinomycin D
      that eliminate all DNA-directed RNA synthesis. No RNA synthesis occurs under the
      same conditions with mitochondria from plants possessing normal (N) cytoplasm or
      with other subcellular fractions from plants with S cytoplasm. The actinomycin D
      resistant RNA synthesis occurs within the mitochondria since the labeling of
      these species is unaffected by inclusion of RNase in the incubation medium and
      since they become completely sensitive to RNase upon lysis of the mitochondria
      with low concentrations of Triton X-100. Two of the actinomycin D-resistant
      products are double stranded. These are 2850 and 900 base pairs in length,
      whereas the remaining two are 2150 and 850 bases. The synthesis of all four RNAs
      occurs in at least five different accessions of S cytoplasm, suggesting it is a
      general feature of S mitochondria. The double-stranded RNAs show homology to
      single-stranded S mitochondrial RNA but not to N mitochondrial RNA. Our
      observations indicate that the replication of these RNAs occurs independently of
      mtDNA and that they thus represent a novel type of inheritable element in
      organelles, an RNA plasmid.

PMID- 16593732
TI  - Discrete wave mechanics: An introduction.
AB  - Discrete wave mechanics is formulated for particles in one-dimensional systems by
      use of a simple finite difference equation. The solutions involve wave vectors
      (instead of wave functions) as well as a newly defined "wave vector energy." In
      the limit, as c --> infinity, the treatment reduces to that of Schrodinger's wave
      mechanics. Specific calculations are made for completely free particles as well
      as for particles confined to a one-dimensional box. The results exhibit a
      striking compatibility with relativistic considerations. The wave vectors show
      properties that can be identified with particles and anti-particles-each possess
      identical probability distributions with energies that add up to zero.

PMID- 16593731
TI  - Molecular devices: Caroviologens as an approach to molecular wires-synthesis and
      incorporation into vesicle membranes.
AB  - Molecular wires, which would allow electron flow to take place between different
      components, are important elements in the design of molecular devices. An
      approach to such species would be molecules possessing an electron-conducting
      conjugated chain, terminal electroactive polar groups, and a length sufficient to
      span a lipid membrane. To this end, bispyridinium polyenes of different lengths
      have been synthesized and their incorporation into the bilayer membrane of sodium
      dihexadecyl phosphate vesicles has been studied. Since they combine the features
      of carotenoids and of viologens, they may be termed caroviologens. Vesicles
      containing the caroviologen whose length approximately corresponds to the
      thickness of the sodium dihexadecyl phosphate bilayer display temperature
      dependent changes of its absorption spectrum reflecting the gel --> liquid
      crystal phase transition of the membrane. The data agree with a structural model
      in which the caroviologens of sufficient length span the bilayer membrane, the
      pyridinium sites being close to the negatively charged outer and inner surfaces
      of the sodium dihexadecyl phosphate vesicles and the polyene chain crossing the
      lipidic interior of the membrane. These membranes may now be tested in processes
      in which the caroviologen would function as a continuous, transmembrane electron
      channel-i.e., as a molecular wire. Various further developments may be envisaged
      along these lines.

PMID- 16593733
TI  - Algebraic K-theory of spaces stratified fibered over hyperbolic orbifolds.
AB  - Among other results, we rationally calculate the algebraic K-theory of any
      discrete cocompact subgroup of a Lie group G, where G is either O(n, 1), U(n, 1),
      Sp(n, 1), or F(4), in terms of the homology of the double coset space Gamma?G/K,
      where K is a maximal cocompact subgroup of G. We obtain the formula K(n)(ZGamma)
      [unk] [unk] congruent with [unk](i=0) (infinity)H(i)(Gamma?G/K; [unk](n-i)),
      where [unk](j) is a stratified system of Q vector spaces over Gamma?G/K and the
      vector space [unk](j)(GammagK) corresponding to the double coset GammagK is
      isomorphic to K(J)(Z(Gamma [unk] gKg(-1))) [unk] Q. Note Gamma [unk] gKg(-1) is a
      finite subgroup of Gamma. Earlier, a similar formula for discrete cocompact
      subgroups Gamma of the group of rigid motions of Euclidean space was conjectured
      by F. T. Farrell and W. C. Hsiang and proven by F. Quinn.

PMID- 16593734
TI  - Inhibition of gene expression in plant cells by expression of antisense RNA.
AB  - Due to the paucity of mutations in biochemical pathways in plants, an alternative
      approach to classical genetics was tested by expressing antisense RNA in plant
      cells. A series of plasmids was constructed with the bacterial gene for
      chloramphenicol acetyltransferase (EC 2.3.1.28) linked in either the sense or
      antisense orientation to several different plant gene promoters. Various ratios
      of sense and antisense chloramphenicol acetyltransferase gene plasmids were
      introduced into plant protoplasts by electric field-mediated DNA transfer
      ("electroporation") and the level of expression in each combination was monitored
      by chloramphenicol acetyltransferase assays. Transcription of antisense RNA was
      found to effectively block the expression of target genes. Thus, the observation
      that antisense RNA inhibits gene expression in bacteria and animal systems has
      been extended to the plant kingdom. Antisense RNA techniques have immediate
      practical applications in both basic research and in plant genetic engineering.

PMID- 16593735
TI  - Efficient in vitro import of a cytosolic heat shock protein into pea
      chloroplasts.
AB  - In order to further our understanding of the targeting of nuclear-encoded
      proteins into intracellular organelles, we have investigated the import of
      chimeric precursor proteins into pea chloroplasts. Two different chimeric
      precursor proteins were produced by in vitro expression of chimeric genes. One
      chimeric precursor contained the transit peptide of the small subunit of soybean
      ribulose 1,5-bisphosphate carboxylase and the mature peptide of the same protein
      from pea. The second contained the same transit peptide plus 13 amino acids of
      the pea mature peptide fused to a cytosolic heat shock protein. The extent of
      import and binding of the two chimeric proteins was examined by using
      quantitative assays and was compared to the import of pea small subunit
      precursor. Both precursor proteins imported well into pea chloroplasts, although
      the extent of import observed with the chimeric small-subunit-heat shock
      precursor was less than that observed with the soybean-pea small subunit
      precursor. The heat shock protein alone did not import into nor bind to
      chloroplasts. The binding of both the chimeric small-subunit-heat shock protein
      and the soybean-pea small subunit precursor to chloroplasts was physiologically
      significant, as shown by the fact that when chloroplasts with bound precursors
      were isolated, these bound precursors could subsequently be imported.

PMID- 16593736
TI  - Chloroplast DNA evidence for the origin of the genus Heterogaura from a species
      of Clarkia (Onagraceae).
AB  - Restriction-site variation in chloroplast DNA was examined in the morphologically
      distinct and monotypic genus Heterogaura and the related speciose genus Clarkia
      (Onagraceae), both native to California. Of the 605 restriction sites surveyed, a
      total of 119 mutations were identified. Of these, 55 were shared by at least two
      species and were used to construct a most parsimonious phylogenetic tree. This
      analysis, as well as one based on a distance metric, provided evidence that
      Heterogaura and Clarkia dudleyana, a member of a phylogenetically advanced
      section, share a more recent common ancestor than either does with any other
      species. The two species are more closely related than nearly all paris of
      Clarkia tested. The origin of Heterogaura from within another genus raises
      important questions about the adequacy of morphological data and suggests that
      the relationships of other well-known monotypic plant genera should be
      reinvestigated.

PMID- 16593737
TI  - Double-stranded gap repair in the photosynthetic prokaryote Synechococcus R2.
AB  - The photosynthetic cyanobacterium Synechococcus R2 is transformed by chimeric
      donor molecules lacking a functional replication origin but containing a region
      of homology to the recipient chromosome. These integrating donor molecules
      consist of a fragment of Synechococcus R2 chromosomal DNA cloned in the
      Escherichia coli vector pBR322 and interrupted by a piece of foreign DNA. During
      integration, this interrupting DNA is often lost by nonreciprocal exchange
      between homologous regions of donor and recipient. When transformed with donor
      molecules containing in vitro-generated double-stranded gaps or deletions as
      large as 20 kilobase pairs in the fragment homologous to the recipient
      chromosome, Synechococcus R2 can repair these lesions by using recipient
      information. Chromosomal DNA of the resulting transformants contains direct
      repeats of the recipient copy on either side of integrated pBR322 DNA. Homologous
      recombination between these repeats generates a circular molecule that can be
      recovered by transformation to E. coli. Plasmids recovered in E. coli contain the
      entire copy of information initially present in the region of the Synechococcus
      recipient corresponding to the donor gap or deletion. We suggest applications of
      this mechanism for cloning of genes identified by transposon mutagenesis.

PMID- 16593738
TI  - Changes in genetic diversity in the red winter wheat regions of the United
      States.
AB  - Pedigree and acreage data were utilized to determine trends in genetic diversity
      of soft red winter (SRW) and hard red winter (HRW) wheats. Four uniformity
      estimates were computed: (a) r(1), the mean relationship among all cultivars
      grown in a given year; (b) r(2), the mean relationship among primary cultivars;
      (c) r(3), the mean relationship of primary cultivars weighted by acreage; and (d)
      r(4), the mean relationship of primary cultivars grown in different years,
      weighted by acreage. In the SRW region, there has been a slow but steady increase
      in relationship among cultivars (r(1) and r(2)). There was a dramatic increase in
      field uniformity (r(3)) during the 1970s, but r(3) had sharply decreased by 1984
      to its lowest point ever (0.22). All uniformity estimates decreased sharply for
      HRW wheats from 1919 to 1949 and have decreased gradually since. Uniformity is
      higher in HRW than in SRW wheats, primarily because of the persistence of a core
      of HRW germ plasm from cultivar ;Turkey,' but the difference is diminishing. Both
      classes appear to be entering a new era of increasing diversity.

PMID- 16593739
TI  - Somatic hybridization in the Gramineae: Saccharum officinarum L. (sugarcane) and
      Pennisetum americanum (L.) K. Schum. (pearl millet).
AB  - Somatic hybrid cell lines with embryogenic capacity were obtained by fusion of
      protoplasts isolated from an embryogenic cell line of sugarcane with inactivated
      protoplasts of an S-(2-aminoethyl)-L-cysteine (Aet-Cys)-resistant cell line of
      pearl millet. Initial selection for putative hybrids was performed by plating
      protoplast-derived microcolonies onto medium containing 300 mug of Aet-Cys per
      ml. Calli growing in the presence of Aet-Cys were screened with respect to their
      electrophoretic pattern of phosphogluconate dehydrogenase (6-phospho-D-gluconate;
      EC 1.1.1.44), a dimeric enzyme. The somatic hybrid calli showed both parental
      homodimer bands plus an intermediate heterodimer band. Somatic hybrid lines were
      characterized further by electrophoretic patterns of shikimate dehydrogenase
      (shikimate; EC 1.1.1.25) and arylesterase (aryl-ester hydrolase; EC 3.1.1.2). All
      cell lines expressed the nuclear genomes of both parents. Use of a maize
      ribosomal DNA probe allowed the identification of diagnostic ribosomal DNA
      fragments in Xba I digests of total DNA in both parents and the somatic hybrids.
      The somatic hybrid lines carried both sugarcane and pearl millet ribosomal DNA
      fragments. The somatic hybrid calli formed somatic embryos. The banding pattern
      of phosphogluconate dehydrogenase from the somatic embryos was similar to that of
      the somatic hybrid calli.

PMID- 16593740
TI  - Discrete wave mechanics: The hydrogen atom.
AB  - The quantum mechanical problem of the hydrogen atom is treated by use of a finite
      difference equation in place of Schrodinger's differential equation. The exact
      solution leads to a wave vector energy expression that is readily converted to
      the Bohr-Rydberg formula. (The calculations here reported are limited to
      spherically symmetric states.) The wave vectors reduce to the familiar solutions
      of Schrodinger's equation as c --> infinity. The internal consistency and
      limiting behavior provide support for the view that the equations employed could
      well constitute an approach to a relativistic formulation of wave mechanics.

PMID- 16593741
TI  - From instability to irreversibility.
AB  - A canonical procedure transforming the unitary evolution group U(t) in a
      contracting semigroup W(t) for phase-space ensembles has been developed for
      Kolmogorov dynamical systems in a series of recent papers. This paper
      investigates the physical meaning of this transformation. We stress that, for
      sufficiently unstable dynamical systems in which phase-space points are
      identified with an arbitrary but finite precision, one must take into account the
      undiscernibility of trajectories having the same asymptotic behavior in the
      future. The fundamental objects of our description are thus bundles of converging
      trajectories. We show that such an ensemble, corresponding to initial conditions
      whose support has finite measure, is then represented by a distribution function
      (called a Boltzmann ensemble) that evolves to equilibrium under the action of a
      markovian semigroup. The usual Gibbs-Koopman ensembles satisfying the Liouville
      equation are recovered as a singular limit. This work validates Boltzmann's
      intuition for a class of unstable dynamical systems and appears as a step toward
      the derivation of equations exhibiting irreversibility at a microscopic level.

PMID- 16593742
TI  - Self-excited mono-ion oscillator.
AB  - We propose self-excitation as a potentially more sensitive technique for studying
      a mono-ion oscillator of frequency v(z) approximately 0.1-100 MHz. This technique
      also makes only low demands on the harmonicity of the ion oscillation. It should
      therefore work with inexpensive, easily constructed rf traps. In our analysis,
      the bound ion between the trap electrodes is represented by an effective circuit
      resembling that of a piezoelectric quartz crystal. The feedback circuit
      developed, when operated below self-excitation threshold, may also make efficient
      electronic cooling of the ion possible, particularly in conjunction with a
      heterodyne feedback scheme. In the super-regenerative mode, the apparatus might
      function as a powerful atomic amplifier of the ion oscillation for an energy as
      low as a fraction of hv(z). These techniques may prove especially useful in
      conjunction with attempts to synthesize in an rf trap a loosely bound anti
      hydrogen atom from a positron and antiproton.

PMID- 16593743
TI  - Immunocytochemical localization of component C of the methylreductase system in
      Methanococcus voltae and Methanobacterium thermoautotrophicum.
AB  - Antibodies were raised against homogeneous preparations of component C of the
      methylreductase system from Methanococcus voltae and Methanobacterium
      thermoautotrophicum. Cells of these organisms were fixed with paraformaldehyde
      and/or glutaraldehyde, sectioned, and labeled with antibodies and colloidal gold
      labeled protein A. In M. voltae the gold particles were predominantly located in
      the vicinity of the cytoplasmic membrane. In rare cases a similar result was
      obtained also with M. thermoautotrophicum. However, in all but a few of the
      ultrathin sections of this bacterium, the label was randomly distributed in the
      cell interior. If one assumes a reliable fixation of all cell components, these
      results would suggest that the two distantly related methanogens studied have
      distinctive patterns for the localization of component C. The results with M.
      voltae are in agreement with recent findings that the methylreductase system is
      involved in the generation of a proton-motive force at the membrane.

PMID- 16593744
TI  - Amino acid sequence of a prothoracicotropic hormone of the silkworm Bombyx mori.
AB  - We have determined the complete amino acid sequence of 4K-PTTH-II, one of three
      forms of the M(r) 4400 prothoracicotropic hormone of the silkworm Bombyx mori,
      active to brainless pupae of Samia cynthia ricini. Like vertebrate insulin, it
      consists of two nonidentical peptide chains (A and B chains). The A chain
      consists of 20 amino acid residues. The B chain is a mixture of four
      microheterogeneous peptides, two of which consist of 28 residues, and the other
      two, of 26 residues. 4K-PTTH-II has considerable sequence homology (40%) with
      human insulin, and it resembles porcine relaxin both in the carboxyl-terminal
      cysteine residue of the A chain and in the amino-terminal pyroglutamic acid
      residue of the B chain. The identical distribution of the six cysteine residues
      also indicates that 4K-PTTH-II belongs to the insulin family.

PMID- 16593745
TI  - Use of monosomics to map cloned DNA fragments in maize.
AB  - Monosomic maize (Zea mays L.) plants were generated using the r-X1 deficiency
      system, and the monosomy was confirmed both genetically and cytologically.
      Genomic DNAs prepared from a group of plants, each monosomic for one chromosome,
      were digested with restriction enzymes, electrophoresed in agarose gels, and
      blotted onto nylon membranes. Hybridization of labeled cloned DNA fragments to
      these blots proved efficient in assigning each fragment to the chromosome from
      which it originated. Cloned DNA has previously contributed to loci detection
      through the use of the restriction fragment length polymorphisms (RFLPs), these
      loci subsequently being arranged into linkage groups by segregation analysis. In
      this study, these linkage groups were assigned to specific chromosomes,
      facilitating the construction of a linkage map for maize containing 112 RFLP
      loci. An additional 35 loci were also assigned to chromosomes by this method;
      however, the linkage relationships of these loci to other RFLP loci on each
      chromosome remains undetermined.

PMID- 16593746
TI  - Flow rates and reaction rates in the Galapagos Rise spreading center hydrothermal
      system as inferred from Ra/Ra in vesicomyid clam shells.
AB  - The (228)Ra/(226)Ra ratios in a previously dated vesicomyid clam shell were used
      to determine that seawater was in contact with mid-oceanic-ridge basalt glass for
      22-45 years prior to arrival to the surface at 350 degrees C at the Galapagos
      Rise Spreading Center. The minimum rate of reaction for the 45-year sojourn time,
      based on a water/rock ratio of 2.8 derived from (226)Ra concentrations, is 8 g of
      basalt altered per kg of seawater per year.

PMID- 16593747
TI  - Entropy, matter, and cosmology.
AB  - The role of irreversible processes corresponding to creation of matter in general
      relativity is investigated. The use of Landau-Lifshitz pseudotensors together
      with conformal (Minkowski) coordinates suggests that this creation took place in
      the early universe at the stage of the variation of the conformal factor. The
      entropy production in this creation process is calculated. It is shown that these
      dissipative processes lead to the possibility of cosmological models that start
      from empty conditions and gradually build up matter and entropy. Gravitational
      entropy takes a simple meaning as associated to the entropy that is necessary to
      produce matter. This leads to an extension of the third law of thermodynamics, as
      now the zero point of entropy becomes the space-time structure out of which
      matter is generated. The theory can be put into a convenient form using a
      supplementary "C" field in Einstein's field equations. The role of the C field is
      to express the coupling between gravitation and matter leading to irreversible
      entropy production.

PMID- 16593748
TI  - Peroxidases depolymerize lignin in organic media but not in water.
AB  - Horseradish peroxidase and milk lactoperoxidase, while unable to degrade either
      synthetic or natural lignins in aqueous solutions, vigorously depolymerize
      polyconiferyl alcohol, milled wood lignin, and kraft pine lignin in dioxane,
      dimethylformamide, or methyl formate containing 5% aqueous buffer (10 mM acetate,
      pH 5). Horseradish peroxidase, solubilized in organic media by chemical
      modification, can also degrade lignin in native lignocellulose (wheat straw).

PMID- 16593749
TI  - Synthesis of an O-glycosylated cell surface protein induced in yeast by alpha
      factor.
AB  - A number of cell surface glycoproteins can be specifically and completely
      released from intact cells of Saccharomyces cerevisiae with 0.5% mercaptoethanol.
      Among these proteins is one with a molecular mass of 22 kDa, which is synthesized
      only in haploid a cells treated with the peptide mating pheromone alpha factor.
      This protein could be radiolabeled in vivo with [2-(3)H]mannose,
      [(14)C]phenylalanine, and [(35)S]sulfate. Its synthesis and export to the cell
      surface were not inhibited by tunicamycin. beta-Elimination released almost all
      radioactivity from the [2-(3)H]mannose-labeled protein, 36% of its radioactivity
      being recovered subsequently as mannose and 43% as a dimannoside. Evidence is
      presented that the 22-kDa O-glycosylated protein is a mating-type specific a cell
      agglutinin.

PMID- 16593750
TI  - Primary photochemistry of iron-depleted and zinc-reconstituted reaction centers
      from Rhodopseudomonas sphaeroides.
AB  - The primary photochemistry of Fe-depleted and Zn-reconstituted reaction centers
      from Rhodopseudomonas sphaeroides R-26.1 was studied by transient absorption
      spectroscopy and compared with native, Fe(2+)-containing reaction centers.
      Excitation of metal-free reaction centers with 30-ps flashes produced the initial
      charge-separated state P(+)I(-) (P(+)BPh(-), where P is the primary donor and BPh
      is bacteriopheophytin) with a yield and visible/near-infrared absorption
      difference spectrum indistinguishable from that observed in native reaction
      centers. However, the lifetime of P(+)I(-) was found to increase approximately 20
      fold to 4.2 +/- 0.3 ns (compared to 205 ps in native reaction centers), and the
      yield of formation of the subsequent state P(+)Q(A) (-) (Q(A) is the primary
      quinone acceptor) was reduced to 47 +/- 5% (compared to essentially 100% in
      native reaction centers). The remaining 53% of the metal-free reaction centers
      were found to undergo charge recombination during the P(+)I(-) lifetime to yield
      both the ground state (28 +/- 5%) and the triplet state P(R) (25 +/- 5%).
      Reconstitution of Fe-depleted reaction centers with Zn(2+) restored the "native"
      photochemistry. Possible mechanisms responsible for the reduced decay rate of
      P(+)I(-) in metal-free reaction centers are discussed.

PMID- 16593751
TI  - Gene-for-gene interactions of five cloned avirulence genes from Xanthomonas
      campestris pv. malvacearum with specific resistance genes in cotton.
AB  - A total DNA clone bank of a strain of Xanthomonas campestris pv. malvacearum
      (Xcm) was constructed in the cosmid vector pSa747 and transfected into
      Escherichia coli. The Xcm strain carries at least nine identifiable avirulence
      (A) genes. Clones in E. coli were mated individually into a recombination
      proficient Xcm isolate carrying no known A genes. Screening was for
      incompatibility on congenic cotton host lines that differ by single specific
      resistance (R) genes. Ten different cosmid clones conferring race-specific
      avirulence were recovered. In most cases, the same A gene clone was recovered
      independently several times. Using the congenic host lines and the merodiploid
      transconjugant pathogen strains, five of the A genes were shown to specifically
      interact, gene-for-gene, with individual R genes in the congenic cotton lines.
      Some A/R gene interactions appeared qualitatively different from others,
      suggesting that the physiological mechanism(s) of gene-for-gene specified
      incompatibility may be unique to the interactive gene pair. All A genes appeared
      to be chromosomally determined, three were found linked on a single 32-kilobase
      clone, and the rest were spaced more than 31 kilobases apart. Colinearity of the
      cosmid inserts with the Xcm recipient (carrying no known A genes) chromosome was
      demonstrated in two of the three tested. This and other evidence suggests that at
      least some A genes in bacteria may have the equivalent of virulence (a) alleles.
      The genetics of race specificity in this phytopathogenic bacterium appeared in
      all respects to be identical to that found in phytopathogenic fungi.

PMID- 16593752
TI  - Molecular cloning of tomato fruit polygalacturonase: Analysis of
      polygalacturonase mRNA levels during ripening.
AB  - The expression of a gene encoding the cell wall-degrading enzyme
      polygalacturonase [poly(1,4-alpha-D-galacturonide) glucanohydrolase, EC 3.2.1.15]
      was characterized during tomato fruit ripening. Polygalacturonase was purified
      from ripe tomato fruit and used to produce highly specific antiserum. Immunoblot
      analyses detected a 45- and a 46-kDa protein in ripe fruit but
      immunoprecipitation of in vitro translation products of mRNA from ripe tomato
      fruit yielded a single 54-kDa polypeptide, suggesting post-translational
      processing. A plasmid cDNA library was prepared from poly(A)(+) RNA isolated from
      ripe tomato fruit. The cDNA library was inserted into a lambda-based expression
      vector, and polygalacturonase cDNA clones were identified by immunological
      screening. Hybrid-select translation experiments indicated that the cDNAs encode
      a 54-kDa in vitro translation product that is specifically immunoprecipitated
      with polygalacturonase antiserum. RNA-blot analysis indicated that the 1.9
      kilobase polygalacturonase mRNA was virtually absent from immature-green fruit,
      accumulated steadily during the ripening process, and was at its highest level in
      red-ripe fruit. There was at least a 2000-fold increase in the level of
      polygalacturonase mRNA between immature-green and red-ripe tomato fruit. These
      studies show that the levels of polygalacturonase mRNA are developmentally
      regulated during tomato fruit ripening.

PMID- 16593753
TI  - Gene-dosage compensation of endosperm proteins in hexaploid wheat Triticum
      aestivum.
AB  - Several aneuploid lines and one intervarietal substitution line of the hexaploid
      wheat Triticum aestivum (2n = 6x = 42; genomes AABBDD) cv. Chinese Spring were
      used to study the effects of different doses of chromosomes 1B, 1D, or 1A on the
      amount of the high molecular weight ("HMW") glutenins and gliadins of endosperm.
      These homeologous chromosomes carry HMW glutenin and gliadin gene clusters on
      their long and short arms, respectively. Increasing the dosage of chromosome 1B
      of Chinese Spring in plants having in their 3n endosperm zero or the normal three
      doses of the homeologue 1D, as well as in plants carrying in their endosperm one
      dose of 1B of the cultivar Timstein, had a dual effect: on one hand, a nonlinear
      increase in the amount of each subunit encoded by the chromosome whose dosage was
      elevated and, on the other hand, a compensating nonspecific decrease in the
      amount of other HMW glutenin and gliadin subunits encoded either by the
      homeoalleles on 1D or by the homoalleles on 1B of Timstein, respectively.
      Deletion of chromosome arm 1BL, which carries only a few HMW glutenin genes, had
      no significant effect on the amount of HMW glutenins encoded by 1DL and HMW
      gliadins encoded by 1DS and 1BS. However, deletion of 1BS or 1DS, each carrying
      many gliadin genes, caused a significant but nonspecific increase in the HMW
      glutenins and gliadins encoded by the remaining arms of 1B and 1D. The possible
      mechanism and evolutionary implications of gene-dosage compensation in polyploid
      wheat are discussed.

PMID- 16593754
TI  - Existence of simply connected algebraic surfaces of general type with positive
      and zero indices.
AB  - In the classification problem of algebraic surfaces of general type, an important
      conjecture states that for simply connected such surfaces Chern numbers satisfy
      the inequality c(1) (2) </= 2c(2) (or equivalently, the index tau </= 0). We
      disprove this conjecture by computing fundamental groups of Galois coverings
      corresponding to generic CP(2) projections of projective embeddings of CP(1) x
      CP(1) related to linear systems [unk]al(1) + bl(2)[unk], a >/= 3, b >/= 2. Also,
      we proved the existence of simply connected minimal surfaces of general type with
      zero index (e.g., c(1) (2) = 2c(2)). Previously, it was conjectured that these
      are exactly the surfaces uniformizable in the polydisk. So this conjecture is
      also disproved.

PMID- 16593755
TI  - Structure and function of a chloroplast DNA replication origin of Chlamydomonas
      reinhardtii.
AB  - Chloroplast DNA replication in Chlamydomonas reinhardtii is initiated by the
      formation of a displacement loop (D-loop) at a specific site. One D-loop site
      with its flanking sequence was cloned in recombinant plasmids SC3-1 and R-13. The
      sequence of the chloroplast DNA insert in SC3-1, which includes the 0.42-kilobase
      (kb) D-loop region, as well as 0.2 kb to the 5' end and 0.43 kb to the 3' end of
      the D-loop region, was determined. The sequence is A+T-rich and contains four
      large stem-loop stuctures. An open reading frame potentially coding for a
      polypeptide of 136 amino acids was detected in the D-loop region. One stem-loop
      structure and two back-to-back prokaryotic-type promoters were mapped within the
      open reading frame. The 5.5-kb EcoRI fragment cloned in R-13 contains the 1.05-kb
      SC3-1 insert and its flanking regions. A yeast autonomously replicating (ARS)
      sequence and an ARC sequence, which promotes autonomous replication in
      Chlamydomonas, have been mapped within the flanking regions [Vallet, J.-M. &
      Rochaix, J.-D. (1985) Curr. Genet. 9, 321-324]. Both R-13 and SC3-1 were active
      as templates in a crude algal preparation that supports DNA synthesis. In this in
      vitro system, chloroplast DNA synthesis initiated near the D-loop site.

PMID- 16593756
TI  - Proton percolation on hydrated lysozyme powders.
AB  - The framework of percolation theory is used to analyze the hydration dependence
      of the capacitance measured for protein samples of pH 3-10, at frequencies from
      10 kHz to 4 MHz. For all samples there is a critical value of the hydration at
      which the capacitance sharply increases with increase in hydration level. The
      threshold h(c) = 0.15 g of water per g of protein is independent of pH below pH 9
      and shows no solvent deuterium isotope effect. The fractional coverage of the
      surface at h(c) is in close agreement with the prediction of theory for surface
      percolation. We view the protonic conduction process described here for low
      hydration and previously for high hydration as percolative proton transfer along
      threads of hydrogen-bonded water molecules. A principal element of the
      percolation picture, which explains the invariance of h(c) to change in pH and
      solvent, is the sudden appearance of long-range connectivity and infinite
      clusters at the threshold h(c). The relationship of the protonic conduction
      threshold to other features of protein hydration is described. The importance of
      percolative processes for enzyme catalysis and membrane transport is discussed.

PMID- 16593757
TI  - Expression of a foreign gene linked to either a plant-virus or a Drosophila
      promoter, after electroporation of protoplasts of rice, wheat, and sorghum.
AB  - The bacterial chloramphenicol acetyltransferase (CAT) gene was expressed in
      protoplasts of three important graminaceous plant species after introduction of
      the gene by electroporation. Gene transfer occurred when high-voltage electric
      pulses were applied either directly or indirectly (without anode contact) to a
      solution containing plasmid DNA and protoplasts of rice, wheat, or sorghum. The
      indirect method was more rapid, resulted in higher protoplast viability, and was
      less subject to contamination than the direct-contact method. Gene expression of
      approximately equal magnitude resulted when the CAT gene was fused to either the
      35S promoter of cauliflower mosaic virus or the copia long terminal repeat
      promoter of Drosophila. Together with recent advances in regeneration of callus
      and whole plants from protoplasts, this system makes it possible to study
      inheritance and expression of genes introduced into graminaceous monocotyledonous
      plants.

PMID- 16593758
TI  - Cloning and nitrate induction of nitrate reductase mRNA.
AB  - Nitrate is the major source of nitrogen taken from the soil by higher plants but
      requires reduction to ammonia prior to incorporation into amino acids. The first
      enzyme in the reducing pathway is a nitrate-inducible enzyme, nitrate reductase
      (EC 1.6.6.1). A specific polyclonal antiserum raised against purified barley
      nitrate reductase has been used to immunoprecipitate in vivo labeled protein and
      in vitro translation products, demonstrating that nitrate induction increases
      nitrate reductase protein and translatable mRNA. A partial cDNA clone for barley
      nitrate reductase has been isolated and identified by hybrid-selected
      translation. RNA blot-hybridization analysis shows that nitrate induction also
      causes a marked increase in the steady-state level of nitrate reductase mRNA.

PMID- 16593759
TI  - Translocation of the precursor of 5-enolpyruvylshikimate-3-phosphate synthase
      into chloroplasts of higher plants in vitro.
AB  - 5-enolPyruvylshikimate-3-phosphate synthase (EPSP synthase; 3-phosphoshikimate 1
      carboxyvinyl-transferase; EC 2.5.1.19) is a chloroplast-localized enzyme of the
      shikimate pathway in plants. This enzyme is the target for the nonselective
      herbicide glyphosate (N-phosphonomethylglycine). We have previously isolated a
      full-length cDNA clone of EPSP synthase from Petunia hybrida. DNA sequence
      analysis suggested that the enzyme is synthesized as a cytosolic precursor (pre
      EPSP synthase) with an amino-terminal transit peptide. Based on the known amino
      terminus of the mature enzyme, and the 5' open reading frame of the cDNA, the
      transit peptide of pre-EPSP synthase would be maximally 72 amino acids long. To
      confirm this prediction and to assay directly for translocation of pre-EPSP
      synthase into chloroplasts in vitro, we cloned the full-length cDNA into an SP6
      transcription system to produce large amounts of mRNA for in vitro translation.
      The translation products, when analyzed by NaDodSO(4)/PAGE autoradiography,
      indicate a relative molecular mass for pre-EPSP synthase of approximately 55 kDa.
      Uptake studies with intact chloroplasts, in vitro, indicate that pre-EPSP
      synthase was rapidly taken up into chloroplasts and proteolytically cleaved to
      the mature approximately 48-kDa enzyme. The transit peptide was shown to be
      essential for import of the precursor enzyme into the chloroplast. To our
      knowledge, post-translational import into chloroplasts of a precursor enzyme
      involved in amino acid biosynthesis has not been reported previously.
      Furthermore, enzymatic analysis of translation products indicates that pre-EPSP
      synthase is catalytically active and has a similar sensitivity to the herbicide
      glyphosate as the mature enzyme. To our knowledge, pre-EPSP synthase represents
      the only example of a catalytically competent chloroplast-precursor enzyme.

PMID- 16593760
TI  - Intense natural selection caused a rapid morphological transition in a living
      marine snail.
AB  - Shell shape and shell thickness of the intertidal snail Littorina obtusata
      changed markedly between 1871 and 1984 in northern New England. Shells collected
      prior to 1900 were high-spired with thin walls, whereas shells collected in 1982
      84 were low-spired with thick walls. An intertidal crab (Carcinus maenas) which
      preys on L. obtusata expanded its range into northern New England around 1900.
      This suggests that the change in snail shell form was a response to predation by
      Carcinus. Field and laboratory experiments demonstrated that the high-spired form
      of L. obtusata, which can still be found in some Maine localities, is more
      vulnerable to predation by Carcinus than is the low-spired form of L. obtusata.
      Electrophoretic comparisons of high- and low-spired populations of L. obtusata
      confirmed that these populations represent different morphological forms of L.
      obtusata rather than different species [Nei's D (unbiased measure of genetic
      distance) = 0.003]. These data demonstrate that classical Darwinian selection can
      produce a rapid morphological transition without speciation.

PMID- 16593761
TI  - Mass extinctions: Sensitivity of marine larval types.
AB  - Developmental types of marine invertebrates may be divided into planktotrophs,
      which feed on suspended food items, and nonplanktotrophs, which do not feed but
      are supplied with nutrients (yolk) parentally; these may represent high mortality
      fecundity and low mortality-fecundity strategies, respectively. Most versions of
      the bolide impact hypothesis of mass extinction propose occlusion of the sun by
      dust or smoke and severance of planktonic food chains for months or a few years,
      and this should select preferentially against planktotrophs. Yet among fossil
      prosobranch gastropods, planktotrophs survived the end-Cretaceous extinction
      equally as well as nonplanktotrophs. Indirect evidence suggests that end-Permian
      extinctions may have selected against planktotrophs but that the effect was
      prolonged over millions of years.

PMID- 16593762
TI  - Complementation of Agrobacterium tumefaciens tumor-inducing aux mutants by genes
      from the T(R)-region of the Ri plasmid of Agrobacterium rhizogenes.
AB  - In this paper we provide information indicating that the agropine-type root
      inducing (Ri) plasmid pRi1855 of Agrobacterium rhizogenes contains functional
      genes for auxin production (aux) in the right transferred DNA (T-DNA) region
      (T(R)-region). These genes were cloned and introduced into the T-region of the
      tumor-inducing (Ti) plasmids of mutants of Agrobacterium tumefaciens carrying an
      aux mutation. Depending on the Ri aux gene present, the oncogenicity of the Ti
      aux-1 and/or aux-2 mutations was restored, showing that the Ri aux genes are able
      to complement the Ti aux genes. Agrobacterium strains with an agropine-type Ri
      plasmid not only cause hairy root on certain plant species, but they also induce
      tumors on other plant species. In this paper it is shown that a mutation in
      either of the aux genes in the Ri plasmid leads to a total loss of tumorigenicity
      and a strongly diminished rhizogenicity of the host bacterium, revealing that the
      aux genes are important for tumor and root induction. Agrobacterium strains
      containing the T(R)-region but not the T(L) (left)-region of the Ri plasmid are
      still tumorigenic on certain plant species but are no longer capable of hairy
      root induction.

PMID- 16593763
TI  - Extraurophyseal distribution of urotensin II immunoreactive neuronal perikarya
      and their processes.
AB  - The use of the unlabeled antibody enzyme method on serially adjacent sections
      permitted the demonstration of urotensin II (UII) and urotensin I (UI)
      immunoreactivities colocalized in most of the cells of the caudal neurosecretory
      system of Catostomus commersoni. The study of the upper regions of the central
      nervous system from the spinal cord anterior to the fifth preterminal vertebral
      region up to and including the brain stem revealed the presence of UII
      immunoreactivity in cerebrospinal fluid-contacting neurons, located ventral to
      the central canal along the entire length of the spinal cord and medulla. Beaded
      nerve fibers were observed projecting to the ventrolateral surface of the spinal
      cord and also forming a seemingly ascending immunoreactive-UII longitudinal
      bundle directed toward the brain. The presence of this "extraurophyseal" system
      of immunoreactive-UII cells and fibers suggests that the UII peptide may be
      released in upper regions of the central nervous system in response to stimuli
      conveyed via the cerebral spinal fluid. Thus, separate functions may be
      postulated for the urophyseal and the cerebral spinal fluid-contacting urotensin
      II systems.

PMID- 16593764
TI  - The growth cones of Aplysia sensory neurons: Modulation by serotonin of action
      potential duration and single potassium channel currents.
AB  - Serotonin (5-HT) closes a specific K channel ("S") in the cell body of Aplysia
      sensory neurons, resulting in a slow excitatory postsynaptic potential and spike
      broadening. To determine whether the S channel is present and can be modulated in
      processes of the neuron other than the cell body, we studied the effects of 5-HT
      on growth cones of sensory neurons in culture by using the patch-clamp technique.
      Simultaneous application of 5-HT to the cell body and to the growth cones of
      sensory neurons produced, in both, a slow depolarization of approximately 5 mV.
      Also, 5-HT produced a lengthening of the duration of action potential in the
      growth cone and cell body by 20-30%. Similar effects were observed in isolated
      growth cones that had been severed from the rest of the neuron, implying that the
      growth cones contain all the molecular components (i.e., receptors, channels,
      cAMP cascade) necessary for 5-HT action. Cell-attached patch-clamp recordings
      demonstrated the presence of S channels in sensory neuron growth cones.
      Application of serotonin to the bath produced long-lasting all-or-none closures
      of these channels in a manner identical to the previously characterized action of
      5-HT in the cell body. Thus, channel modulation is not restricted to the cell
      body and probably occurs throughout the sensory neuron. This strengthens the view
      that S-channel modulation may also occur at the sensory neuron presynaptic
      terminal, where it could play a role in the presynaptic facilitation produced by
      5-HT.

PMID- 16593765
TI  - Directly observed relations in complete galaxy samples and the predictions of
      redshift-distance power laws.
AB  - Directly observed relations in complete galaxy samples (apparent magnitude or
      diameter vs. redshift) are compared with the predictions of redshift-distance
      power laws. The predictions are obtained by an objective, nonparametric,
      statistically uniform, and fully reproducible procedure. In all cases the linear
      law fits even more poorly than a cubic law, and the optimal law is approximately
      quadratic. Even a 1.2 power law is conspicuously better-fitting than a linear
      law. The results of the present study in terms of directly measured quantities
      are consistent with and confirm earlier studies in terms of theoretical
      quantities such as absolute magnitudes and diameters. They show that there is no
      positive evidence for the Hubble law in manifestly fair galaxy samples and that
      the law can be reconciled with the data in complete samples only, if at all, by
      the adjunction of a tissue of ancillary hypotheses, none of which is capable of
      direct observational substantiation.

PMID- 16593766
TI  - Mitochondrial DNA changes in abnormal growth (nonchromosomal stripe) mutants of
      maize.
AB  - The genetic analysis of higher plant mitochondria has been limited by a scarcity
      of identified mutations with known progenitors. Correspondingly, few molecular
      studies have been directed at types of plant mitochondrial variation other than
      cytoplasmic male sterility. The maternally inherited nonchromosomal stripe (NCS)
      mutants of maize have profound deleterious effects on plant growth and yield. We
      report specific alterations in mitochondrial DNA (mtDNA) for two independent,
      phenotypically distinct NCS mutants. NCS2 plants have a distinctive 21-kilobase
      Xho I mtDNA band and very reduced amounts of DNA in an 8-kilobase band that is
      present in the progenitor. NCS3 plants have a distinctive 20-kilobase Xho I band
      and a reduction in a 16-kilobase band. Our studies confirm that the affected
      organelle in NCS plants is the mitochondrion. Because NCS-type plants appear with
      a certain frequency in a particular line (WF9), this line is a potential source
      of additional mutations for functional and molecular analyses of maize
      mitochondrial genes.

PMID- 16593767
TI  - Monte Carlo estimation of the electric field in stellarators.
AB  - The BETA computer codes have been developed to study ideal magnetohydrodynamic
      equilibrium and stability of stellarators and to calculate neoclassical transport
      for electrons as well as ions by the Monte Carlo method. In this paper a
      numerical procedure is presented to select resonant terms in the electric
      potential so that the distribution functions and confinement times of the ions
      and electrons become indistinguishable.

PMID- 16593768
TI  - Location of the cyclohexene ring of the chromophore of bacteriorhodopsin by
      neutron diffraction with selectively deuterated retinal.
AB  - We report on the location of the cyclohexene ring of the retinylidene chromophore
      of bacteriorhodopsin projected onto the plane of the membrane. For this purpose,
      partially deuterated retinal was synthesized containing 11 deuterons at the
      following positions of the cyclohexene ring: one at C-2, two at C-4, three at C
      16, three at C-17, and two at C-18. The partially deuterated retinal was
      incorporated biosynthetically during growth of the bacteria by using the mutant
      JW5, which is deficient in the synthesis of retinal. Undeuterated samples were
      prepared in the same way. Characterization by x-ray diffraction and absorption
      spectroscopy showed that these samples are identical to native purple membranes
      as judged by these criteria. A Fourier difference map was calculated from the
      differences in in-plane diffraction intensities between the deuterated and
      undeuterated dark-adapted membrane samples. Model calculations showed that the
      observed difference density had the amplitude expected for a label containing 11
      deuterons. At 8.7 A resolution, the map shows one major peak with the center of
      mass of the deuterated ring in the interior of the molecule between helices 3, 4,
      5, and 6. Based on this result and on our previous work on the location of the
      middle of the polyene chain, we conclude that the COOH-terminal helix G, to which
      retinal is attached at lysine-216, is either helix 2 or helix 6.

PMID- 16593769
TI  - Biosynthesis of zeatin from N-(Delta-isopentenyl)adenine in Actinidia: Sites and
      seasonal changes in activity.
AB  - In Actinidia arguta (hardy kiwifruit) plants, the potential to accumulate the
      cytokinin zeatin (io(6)Ade) during feeding with a precursor, N(6)-(Delta(2)
      isopentenyl)adenine (i(6)Ade), varies depending on the tissue. This can be
      demonstrated by incubating explants for 24 hr on a basal nutrient medium
      supplemented with 30 muM i(6)Ade and then extracting the tissues and analyzing
      cytokinin contents using HPLC methodology. Under these conditions, the potential
      for io(6)Ade accumulation in tissue slices from growing roots was 93 nmol/g at
      the root tip, >200 nmol/g immediately behind the tip (1.0-mm diameter),
      approximately 100 nmol/g in 2-mm diameter root, and progressively lower in older
      tissues. A similar gradient of io(6)Ade accumulation was detected in growing
      stems, with relatively low activity (40 nmol/g) in the terminal 0.5 cm,
      approximately 170 nmol/g in the 5- to 15-cm interval, and about 25 nmol/g in stem
      tissues taken 15-100 cm from the tip. Growing leaves accumulated little io(6)Ade
      (7-26 nmol/g) during feeding, as did fruits (0-8 nmol/g) at various stages of
      development and maturation. Seasonally, root activity was detected as early as
      March 1, whereas stem activity did not appear until March 15. Thus, the
      activation of i(6)Ade metabolism in both of these organs preceded sap flow (March
      29) and bud break (April 16) by several weeks. The results suggest that root and
      stem tissues may be sites of cytokinin biosynthesis in growing Actinidia plants
      and that cytokinin production may not be the critical factor controlling the
      beginning of shoot growth in the spring.

PMID- 16593770
TI  - Use of monoclonal antibodies in the purification and characterization of 1
      aminocyclopropane-1-carboxylate synthase, an enzyme in ethylene biosynthesis.
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) synthase (EC 4.4.1.14), extracted from
      tomato pericarp tissue, was purified 6500-fold by conventional and high
      performance liquid chromatography. Two-dimensional gel electrophoresis of this
      preparation indicated that ACC synthase activity was associated with a protein
      band at 50 kDa, a value consistent with size determinations by gel filtration.
      Monoclonal antibodies against ACC synthase were obtained from murine hybridoma
      cell lines. These antibodies recognized the native enzyme, as shown with an
      immunoprecipitation assay. A monoclonal IgG immunoaffinity gel was used to
      isolate, from a relatively crude enzyme preparation, a single protein, which
      migrated at 50 kDa in a NaDodSO(4)/polyacrylamide gel. In vivo labeling of
      wounded tomato pericarp tissue with [(35)S]methionine followed by immunoaffinity
      purification of ACC synthase yielded a radioactive protein of 50 kDa. We conclude
      that the 50-kDa protein represents ACC synthase in extracts of wounded tomato
      pericarp tissue.

PMID- 16593771
TI  - Toward a physical map of the genome of the nematode Caenorhabditis elegans.
AB  - A technique for digital characterization and comparison of DNA fragments, using
      restriction enzymes, is described. The technique is being applied to fragments
      from the nematode Caenorhabditis elegans (i) to facilitate cross-indexing of
      clones emanating from different laboratories and (ii) to construct a physical map
      of the genome. Eight hundred sixty clusters of clones, from 35 to 350 kilobases
      long and totaling about 60% of the genome, have been characterized.

PMID- 16593772
TI  - Facilitatory transmitters and cAMP can modulate accommodation as well as
      transmitter release in Aplysia sensory neurons: Evidence for parallel processing
      in a single cell.
AB  - Presynaptic facilitation of transmission from sensory to motor neurons
      contributes significantly to behavioral sensitization of defensive withdrawal
      reflexes in Aplysia. Presynaptic facilitation is associated with a decrease in
      the serotonin-sensitive K(+) conductance. This decrease broadens the presynaptic
      action potential. In addition, the procedures that cause facilitation-stimulation
      of the connective (the pathway from the tail and head), application of modulatory
      transmitters, or injection of cAMP-also increase the excitability of the sensory
      neurons as tested with intracellular depolarizing pulses injected into the cell
      body. The increased excitability is reflected in a decreased threshold for
      generating action potentials and a reduction in accommodation to prolonged
      constant current stimuli. By influencing the excitability of the peripheral
      processes of the sensory neurons, stimulation of the connectives or serotonin
      also produces a small enhancement of the response of the sensory neurons to a
      tactile stimulus applied to the siphon. The excitability changes appear to
      result, at least in part, from the same cellular mechanisms that lead to
      broadening of the action potential, a cAMP-mediated closure of K(+) channels.
      Therefore, these findings indicate that the same class of mechanisms can, in
      principle, have a dual action and provide further evidence for parallel
      processing in the modulation of transmitter release from a single neuron.

PMID- 16593773
TI  - Nitrate reductase from squash: cDNA cloning and nitrate regulation.
AB  - The assimilation of nitrate in plants involves the reduction of nitrate to
      ammonia in two steps. The first step requires nitrate reductase, a nitrate
      inducible enzyme. When seedlings of squash (Cucurbita maxima L.) were treated
      with nitrate, both nitrate reductase activity and protein were induced in the
      cotyledons. Poly(A)(+) RNA was prepared from cotyledons of nitrate-treated
      seedlings and was used to construct a lambdagt11 cDNA library. Using antibodies
      from mice immunized against purified nitrate reductase from squash, a recombinant
      lambda phage was isolated that encoded part of the nitrate reductase mRNA. The
      antigens produced by the recombinant phage were used to affinity purify anti
      nitrate reductase antibody from ascites fluid of immunized mice. The purified
      antibody bound to nitrate reductase protein on immunoblots and immunoprecipitated
      the enzyme from squash protein extracts. The cDNA insert (1.2 kilobases)
      hybridized to a 3.2-kilobase RNA that was 120-fold more abundant in nitrate
      induced cotyledons compared with the uninduced tissue.

PMID- 16593774
TI  - Site-specific mutagenesis of the calcium-binding photoprotein aequorin.
AB  - The luminescent protein aequorin from the jellyfish Aequoria victoria emits light
      by an intramolecular reaction in the presence of a trace amount of Ca(2+). In
      order to understand the mechanism of the reaction, a study of structure-function
      relationships was undertaken with respect to modifying certain of its amino acid
      residues. This was done by carrying out oligonucleotide-directed site-specific
      mutagenesis of apoaequorin cDNA and expressing the mutagenized cDNA in
      Escherichia coli. Amino acid substitutions were made at the three Ca(2+)-binding
      sites, the three cysteines, and a histidine in one of the hydrophobic regions.
      Subsequent assay of the modified aequorin showed that the Ca(2+)-binding sites,
      the cysteines, and probably the histidine all play a role in the bioluminescence
      reaction of aequorin.

PMID- 16593775
TI  - Ultrasonic absorption evidence for enhanced volume fluctuations in the tobacco
      mosaic virus protein helical aggregate.
AB  - The increased ultrasonic absorption brought about by self-assembly of
      biomolecules is analyzed for the assembly process from the 20S aggregate to the
      helical rod of tobacco mosaic virus protein in solution, designated here as the
      20S --> P-helix transition. The analysis is based on theoretical developments in
      ultrasonic relaxation spectrometry presented previously and illustrates the
      possibility that this technique can be used for characterizing fluctuations. The
      analysis makes use of NMR data for the system in solution and of x-ray
      diffraction data for the closely related transition from the two-ring disk to the
      virion. These x-ray data comprise the high-resolution structures and the Debye
      Waller temperature factors of the main chain atoms of both the two-ring disk in
      crystals and the virion in oriented gel form. First, reduced ultrasonic spectra
      are obtained for the 4S, 20S, and helical rod aggregates. The fluctuation
      enhancement factor for the helical rod is determined independently of any
      deconvolution into normal modes of relaxation and is shown not to depend on the
      particular procedure of reduction employed. The increase of ultrasonic absorption
      in the 20S --> P-helix transition primarily reveals enhancement of the relaxing
      system's normal-mode volume fluctuations. The observed relaxations probably
      involve one conformational process per subunit. The normal-mode volume
      fluctuations are then estimated from a bimodal least-squares best fit to the
      data, and a lower bound for the reaction volume associated with the fast steps is
      obtained. Two mechanisms are considered as follows: (i) a destabilization process
      in which the free-energy difference between two states is reduced and (ii) an
      increase in reaction volumes of local conformation changes in the helical
      aggregate, resulting from the formation of a "carboxyl cage-like" structure and
      from the change in environment produced inside the cage. Increased reaction
      volumes would not be detected with x-ray diffraction. The possible occurrence of
      fluctuations at the RNA binding site raises the question of whether a quaternary
      structure that exhibits significant conformational fluctuations must be present
      for the binding of the nucleic acid.

PMID- 16593776
TI  - Isotope effect on electron transfer in reaction centers from Rhodopseudomonas
      sphaeroides.
AB  - Previous ENDOR studies on reaction centers from Rhodopseudomonas sphaeroides have
      shown the presence of two hydrogen-bonded protons associated with the primary,
      ubiquinone, acceptor Q(A). These protons exchange with deuterons from solvent
      (2)H(2)O. The effect of this deuterium substitution on the charge-recombination
      kinetics (BChl)(2) (+)Q(A) (-) --> (BChl)(2)Q(A) has been studied with a
      sensitive kinetic difference technique. The electron-transfer rate was found to
      increase with deuterium exchange up to a maximum Deltak/k of 5.7 +/- 0.3%. The
      change in rate was found to have an exchange time of 2 hr, which matched the
      disappearance of the ENDOR lines due to the exchangeable protons. These results
      indicate that these protons play a role in the vibronic coupling associated with
      electron transfer. A simple model for the isotope effect on electron transfer
      predicts a maximum rate increase of 20%, which is consistent with the
      experimental results.

PMID- 16593777
TI  - Speciation by monobrachial centric fusions.
AB  - Fixation of centric fusions in natural populations often encounters minimal
      meiotic problems due to the ability of trivalents to segregate normally;
      therefore, little sterility barrier is achieved between a founder population and
      the parental stock. However, a strong sterility barrier can develop between
      different founder populations fixed for centric fusions that are monobrachially
      homologous in the resulting biarmed chromosomes (one arm is homologous but the
      other is nonhomologous). Hybridization through secondary contact then results in
      complex multivalents, which encounter problems in segregation and produce
      unbalanced gametes. Speciation mediated by centric fusions is a peripatric
      speciation model that does not postulate populational phenomena atypical of those
      characteristic of most mammals. The model appears applicable to a diversity of
      mammalian taxa such as bats of the Rhogeessa tumida-parvula complex, shrews of
      the Sorex araneus complex, and rodents of the Mus musculus and Rattus rattus
      complexes.

PMID- 16593778
TI  - Insertion sequence elements of Pseudomonas savastanoi: Nucleotide sequence and
      homology with Agrobacterium tumefaciens transfer DNA.
AB  - Two types of transposable elements, IS51 and IS52 (IS, insertion sequence), were
      found in Pseudomonas syringae subsp. savastanoi (P. savastanoi) that
      spontaneously insert into and inactivate iaaM; the insertion results in the loss
      of indoleacetic acid production and attenuation of virulence. The nucleotide
      sequences of both IS elements have sizes and structural features common to other
      prokaryotic IS elements; IS51 is 1311 base pairs (bp) long and has terminal
      inverted repeats of 26 bp; IS52 is 1209 bp long and has terminal inverted repeats
      of 10 bp with a 1 bp mismatch. In the insertion involving IS51, the trinucleotide
      sequence CAG is duplicated within iaaM sequences at the recombination junction;
      in those involving IS52 the tetranucleotide sequences TTAG or CTAG are duplicated
      within iaaM sequences at the recombination junction. A copy of IS51 occurs 2.5
      kilobases downstream from IaaH. In contrast to the high copy number of IS51 in
      the genome of the bacterium, only a few copies of IS52 are present. No nucleotide
      sequence homology was found between IS51 and IS52. However, a striking nucleotide
      sequence homology was found between a 531-bp region of IS51 and a portion of the
      central region of transfer DNA (T-DNA) in the octopine plasmid pTi15955 from
      Agrobacterium tumefaciens. These observations, together with our earlier finding
      on the homology between iaaM and iaaH and between gene 1 and gene 2 of transfer
      DNA, further suggest that genes for indoleacetic acid production in the two
      systems have a common origin.

PMID- 16593779
TI  - Action-potential duration and the modulation of transmitter release from the
      sensory neurons of Aplysia in presynaptic facilitation and behavioral
      sensitization.
AB  - Presynaptic facilitation of transmitter release from Aplysia sensory neurons is
      an important contributor to behavioral sensitization of the gill and siphon
      withdrawal reflex. The enhanced release is accompanied by reduction of the
      serotonin-sensitive S current in the sensory neurons and a consequent increase in
      duration of the presynaptic action potential (ranging from 10% to 30%). We find
      that changes of similar magnitude in the duration of depolarizing voltage-clamp
      steps in sensory neurons in intact abdominal ganglia yield increases in synaptic
      potentials of 45-120%. In dissociated cell culture, these changes lead to
      increases of 25-60% in the synaptic potential. Prolongation of presynaptic
      depolarization using voltage clamp or prolongation of the duration of the action
      potential by K(+)-channel blockers leads to prolongation of the time-to-peak of
      the synaptic potentials; similar changes in time-to-peak occur during presynaptic
      facilitation. The time-to-peak is not changed by homosynaptic depression or by
      changing the Ca(2+) concentration, procedures that alter release without changing
      the duration of the action potential. Preventing the spike from broadening by
      voltage clamping the presynaptic neuron substantially reduces or blocks the
      facilitation. These results suggest that broadening of the action potential
      during facilitation is a causal factor in the enhancement of transmitter release.

PMID- 16593780
TI  - Satellite tobacco ringspot virus RNA: A subset of the RNA sequence is sufficient
      for autolytic processing.
AB  - The satellite RNA of tobacco ringspot virus depends upon tobacco ringspot virus
      for its replication and source of coat protein. The satellite RNA reduces virus
      accumulation and the severity of virus-induced symptoms. Repetitive sequence,
      dimeric, and higher forms of the satellite RNA are known to autolytically process
      to form biologically active monomeric RNA of 359 nucleotide residues [Prody, G.
      A., Bakos, J. T., Buzayan, J. M., Schneider, I. R. & Bruening, G. (1986) Science
      231, 1577-1580], with a 5'-hydroxyl and a 2',3'-cyclic phosphodiester as the new
      terminal groups. We show here that transcripts of full-length and truncated DNA
      clones of the satellite RNA sequence also process in a nonenzymic reaction. One
      such transcript was an RNA that has about one-fourth of the satellite RNA
      sequence, representing the 3'-terminal and 5'-terminal portions of monomeric RNA
      joined in the junction that is cleaved in dimeric RNA. This RNA autolytically
      processed more efficiently than molecules with a larger proportion of the
      satellite RNA nucleotide sequence.

PMID- 16593781
TI  - Stoichiometric model of the photosynthetic unit of Ectothiorhodospira
      halochloris.
AB  - A stoichiometric model of the photosynthetic unit of Ectothiorhodospira
      halochloris has been obtained by means of scanning transmission electron
      microscope mass determination and mass mapping in conjunction with polyacrylamide
      gel electrophoresis. One reaction center, consisting of four single polypeptides,
      including one cytochrome, is surrounded by six identical light-harvesting
      complexes, each containing three polypeptides with 2:2:2 stoichiometry. This
      stoichiometric model was incorporated into the three-dimensional structure of the
      photosynthetic unit as derived from surface relief reconstructions of the two
      surfaces of shadowed membranes. The reaction center protrudes substantially from
      both membrane surfaces and has the cytochrome attached to the periplasmic face in
      a noncentrosymmetric fashion. The reaction center may assume various orientations
      within the photosynthetic complexes.

PMID- 16593782
TI  - Indole-3-acetic acid and fusicoccin cause cytosolic acidification of corn
      coleoptile cells.
AB  - Microelectrodes were used to measure simultaneously the effects of indole-3
      acetic acid (IAA) on membrane potential and cytosolic pH of corn coleoptile
      cells. IAA caused an initial depolarization followed by hyperpolarization, the
      latter displaying rhythmic oscillations. The extent of the changes in membrane
      potential was dependent on IAA concentration, and hyperpolarization, but not
      depolarization, could be detected with concentrations of IAA as low as 10 nM.
      Membrane hyperpolarization was preceded by a decrease in cytosolic pH. The
      decrease commenced approximately 5 min after adding IAA and continued for 15-20
      min before reaching a new steady state approximately 0.1 pH unit lower than the
      original pH. The decrease in pH was readily detectable after treatment with 0.1
      muM IAA. Fusicoccin and acetate, which, like IAA, induce elongation growth,
      caused a similar drop in cytosolic pH and subsequent membrane hyperpolarization,
      the decrease in pH commencing within seconds. The addition of fusicoccin to IAA
      treated cells resulted in a further cytosolic acidification and membrane
      hyperpolarization. The two substances probably change cytosolic pH via different
      mechanisms. The results imply that one of the primary effects of auxins in
      coleoptiles is to lower cytosolic pH.

PMID- 16593783
TI  - Bioluminescence in soybean root nodules: Demonstration of a general approach to
      assay gene expression in vivo by using bacterial luciferase.
AB  - Two plasmid vectors pFIT001 and pPALE001, containing luxAB genes encoding
      bacterial luciferase [alkanal, reduced-FMN:oxygen oxidoreductase (1
      hydroxylating, luminescing), EC 1.14.14.3] from Vibrio harveyi, have been
      constructed. Escherichia coli carrying derivatives of pFIT001 with DNA inserts in
      the unique EcoRI site located in luxB form "dark" colonies that can be readily
      distinguished from the bioluminescent or "bright" colonies. In contrast,
      promoterless pPALE001 is used as a promoter-search vector based on
      bioluminescence. The control and regulation of gene expression can be analyzed in
      vivo using promoter-luxAB fusions by a variety of simple methods, including a
      technique called "luxdot." As an example, we have introduced nitrogenase nifD and
      nifH promoter-luxAB fusions into the Bradyrhizobium japonicum chromosome and
      shown symbiotically regulated bioluminescence in soybean root nodules. B.
      japonicum transconjugants containing a single copy per genome of the nif promoter
      controlled luciferase structural genes did not produce light in free-living
      cultures, but the same transconjugants did express bioluminescence in root
      nodules that was strong enough to be detected by the naked eye.

PMID- 16593784
TI  - The cloning, genetic mapping, and expression of the constitutive sucrose synthase
      locus of maize.
AB  - Two differentially expressed genes encode isoenzymes of sucrose synthase in Zea
      mays. A clone of the shrunken 1 (Sh1) locus, the structural gene for the major
      endosperm form of sucrose synthase, was used to isolate a genomic clone of
      constitutive sucrose synthase (Css), the structural gene for the isoenzyme
      expressed in embryo and other tissues. The Css clone was positively identified by
      RNA blot analysis of RNA from wild type and a sh1 deletion stock and by analysis
      of the in vitro translation product of hybrid-selected mRNA. Southern blot
      analysis of DNA from monosomic plants derived from an r-x1 stock, coupled with
      restriction fragment length polymorphism mapping, placed the Css gene 32 map
      units from Sh1 on chromosome 9. In seedling tissues, Css mRNA is present at
      higher levels than Sh1 mRNA. Expression of both Sh1 and Css in root tissue is
      enhanced by anaerobic conditions, although Css is induced to a lesser extent than
      is Sh1. Thus, Css appears to be expressed constitutively, whereas Sh1 is
      expressed at high levels only in response to specific developmental and
      environmental stimuli.

PMID- 16593785
TI  - Structural properties of double-stranded RNAs associated with biological control
      of chestnut blight fungus.
AB  - Double-stranded RNAs (ds RNAs) are thought to be the cytoplasmic determinants
      responsible for the phenomenon of transmissible hypovirulence in the chestnut
      blight fungus Endothia parasitica [Murr.] Anderson. The three major ds RNA
      components associated with the North American hypovirulent strain, Grand Haven 2,
      were characterized with respect to molecular-hybridization specificity and RNase
      T1-digestion patterns. The large (L-RNA; approximately 9 kilobase pairs) and
      middle-sized (M-RNA; approximately 3.5 kilobase pairs) ds RNA components cross
      hybridized under stringent conditions and exhibited indistinguishable partial and
      complete RNase T1 digestion patterns relative to their 5' and 3' termini. These
      results suggest that M-RNA was derived from L-RNA by an internal deletion event.
      The small (S-RNA; approximately 1 kilobase pair) RNA was unrelated to L- and M
      RNA by these criteria. However, all three ds RNA components contained RNase T1
      resistant oligonucleotides at one 5' terminus and at the corresponding 3'
      terminus of the complementary strand. These RNase T1-resistant species exhibited
      properties consistent with stretches of poly(uridylic acid) and poly(adenylic
      acid), respectively. The combined results are discussed in terms of the
      structural organization of hypovirulence-associated ds RNA molecules and their
      similarities to "double-stranded" RNA molecules observed in plant and animal
      cells infected with single-stranded RNA viruses.

PMID- 16593786
TI  - Distance between two active-site lysines of ribulose bisphosphate carboxylase
      from Rhodospirillum rubrum.
AB  - In the absence of a three-dimensional structure of ribulose-bisphosphate
      carboxylase/oxygenase [3-phospho-D-glycerate carboxy-lyase(dimerizing), EC
      4.1.1.39], we have probed the distance between two active-site lysyl residues
      (Lys-166 and Lys-329) of the Rhodospirillum rubrum enzyme with 4,4'
      diisothiocyano-2,2'-disulfonate stilbene, a covalent cross-linking reagent that
      spans 12 A. The reagent rapidly inactivated the carboxylase, and a competitive
      inhibitor provided substantial protection. To remove products arising from
      intersubunit or intermolecular cross-linking, the inactivated enzyme was
      subjected to gel filtration in the presence of urea. Inspection of a tryptic
      digest of the isolated monomeric fraction revealed that more than half of the
      incorporated reagent was associated with a single peptide. This peptide was
      purified by gel filtration, followed by high HPLC. Compositional and sequence
      analyses of the purified peptide established that it was composed of two chains,
      encompassing positions 149-168 and 314-337 of the original protein subunit and
      connected by a cross-link between Lys-166 and Lys-329. Thus, the two active-site
      lysines of the carboxylase can be juxtaposed within 12 A, a finding that is
      consistent with their purported proximity to ribulose bisphosphate in the enzyme
      substrate complex. The cross-link was not formed when the carboxylase was treated
      with the reagent either in the presence of a transition-state analogue
      (carboxyarabinitol bisphosphate) or in the absence of CO(2) and Mg(2+),
      conditions under which the enzyme exists in a deactivated form.

PMID- 16593787
TI  - Role of charge-transfer states in bacterial photosynthesis.
AB  - Photon echo, photon-echo excitation, and "hole-burning" data recorded in the 800
      990 nm region of Rhodobacter sphaeroides R26 and Rhodopseudomonas viridis
      reaction centers are reported. The primary process in these reaction centers,
      following excitation, was found to occur in approximately 25 fsec; the long
      wavelength band of the primary electron donor (P) was largely homogeneously
      broadened. In accordance with our previous explanation of hole-burning and photon
      echo measurements on Rb. sphaeroides [Meech, S. R., Hoff, A. J. & Wiersma, D. A.
      (1985) Chem. Phys. Lett. 121, 287-292], we interpret this as resulting from a
      dephasing of the excitation in P into a background of strongly coupled charge
      transfer states. The previously reported picosecond lifetime of the excited P
      state is assigned to decay of these strongly mixed states. Further, a coupling
      between P and an adjacent bacteriochlorophyll was observed. The extent of this
      coupling and the role of charge-transfer states in the functioning of reaction
      centers is discussed.

PMID- 16593788
TI  - Genetically engineered mutant of the cyanobacterium Synechocystis 6803 lacks the
      photosystem II chlorophyll-binding protein CP-47.
AB  - CP-47 is absent in a genetically engineered mutant of cyanobacterium
      Synechocystis 6803, in which the psbB gene [encoding the chlorophyll-binding
      photosystem II (PSII) protein CP-47] was interrupted. Another chlorophyll-binding
      PSII protein, CP-43, is present in the mutant, and functionally inactive PSII
      enriched particles can be isolated from mutant thylakoids. We interpret these
      data as indicating that the PSII core complex of the mutant still assembles in
      the absence of CP-47. The mutant lacks a 77 K fluorescence emission maximum at
      695 nm, suggesting that the PSII reaction center is not functional. The absence
      of primary photochemistry was indicated by EPR and optical measurements: no
      chlorophyll triplet originating from charge recombination between P680(+) and
      Pheo(-) was observed in the mutant, and there were no flash-induced absorption
      changes at 820 nm attributable to chlorophyll P680 oxidation. These observations
      lead us to conclude that CP-47 plays an essential role in the activity of the
      PSII reaction center.

PMID- 16593789
TI  - Male and female stem cells and sex reversal in Hydra polyps.
AB  - Single interstitial stem cells of male polyps of Hydra magnipapillata give rise
      to clones that differentiate either male or female gametes. To test the sexual
      stability of these clones, stem cells were recloned. The results indicate that
      stem cells from female clones are stable in their sexual differentiation
      capacity; male stem cells, by comparison, switch sexual phenotype at the rate of
      10(-2) per cell per generation. As a result, female polyps contain only female
      stem cells; male polyps contain a mixture of male and female stem cells. A model
      is presented in which the sexual phenotype of Hydra polyps is controlled by (i)
      the switching rate of male and female stem cells and (ii) the repression of
      female differentiation by male stem cells.

PMID- 16593790
TI  - Evolutional and ecological implications of the properties of deep-sea barophilic
      bacteria.
AB  - The rate of reproduction of deep-sea bacteria from six different capture depths
      between 1957 and 10,476 meters was studied as a function of temperature and
      pressure. The results showed the following: the true deep-sea bacteria of
      different depths have several characteristics, presumably evolutionally derived,
      distinguishing them from each other and from bacteria of atmospheric-pressure
      environments; pressure plays a significant role in determining the distribution
      of oceanic life; and pressure-adapted bacteria are easily recovered from and
      ubiquitous in the deep ocean. Organisms evolving in habitats of different
      temperatures and pressures need to be studied to understand the physical limits
      of life, the distribution of life within the earth and its oceans, the role of
      organisms in organic diagenesis and petroleum formation, and the possible
      existence of life on and within other planets.

PMID- 16593791
TI  - Expression of the nodulation gene nodA in Rhizobium meliloti and localization of
      the gene product in the cytosol.
AB  - The nodA gene of Rhizobium meliloti encodes a 21.8-kDa protein, which is
      conserved in several Rhizobium species. We overproduced the nodA protein as a
      fusion product with a portion of the lambda cI repressor in Escherichia coli.
      This fusion protein was purified from inclusion bodies by gel and hydroxyapatite
      chromatography in the presence of NaDodSO(4). Monospecific polyclonal antibodies
      against the hybrid protein were used to detect the nodA protein in the cytosol of
      E. coli and R. meliloti by immunoblotting. In contrast to experiments with
      antibodies against the R. meliloti nodC membrane protein, the alfalfa-R. meliloti
      nodulation was not affected by the addition of anti-nodA antibodies to medium and
      inoculum. This suggests that the nodA protein is located within the cell and is
      therefore not accessible to antibodies. The expression of the nodA gene is
      induced in R. meliloti by various compounds present in the exudate of leguminous
      plants, particularly by the flavone luteolin. We show that the plant hormone
      trigonelline also has some inducing activity. The nodC protein was further
      localized in the membrane fraction of R. meliloti. Our experiments demonstrate
      that the nodC transmembrane protein is not necessary for the uptake of the
      compounds inducing the synthesis of the nodA protein. The nodA and the nodC
      proteins were also detected in mature nodules. During nodule development, the
      nodC protein may be processed to a 34-kDa protein.

PMID- 16593792
TI  - Isolation of a photosystem II reaction center consisting of D-1 and D-2
      polypeptides and cytochrome b-559.
AB  - A photosystem II reaction center complex consisting of D-1 and D-2 polypeptides
      and cytochrome b-559 was isolated from spinach grana thylakoids, treated with 4%
      (wt/vol) Triton X-100, by ion-exchange chromatography using DEAE-Toyopearl 650S.
      The isolated complex appears to contain five chlorophyll a, two pheophytin a, one
      beta-carotene, and one or two cytochrome b-559 heme(s) (molar ratio) and exhibits
      a reversible absorbance change attributable to the photochemical accumulation of
      reduced pheophytin typical for the intermediary electron acceptor of photosystem
      II reaction center. These results strongly suggest that the site of primary
      charge separation in photosystem II is located on the heterodimer composed of D-1
      and D-2 subunits.

PMID- 16593793
TI  - Expression and assembly of functional bacterial luciferase in plants.
AB  - The luxA and luxB structural genes of Vibrio harveyi luciferase [alkanal,reduced
      FMN:oxygen oxidoreductase (1-hydroxylating, luminescing), EC 1.14.14.3] were
      introduced into a plant expression vector and transferred into tobacco and carrot
      cells by Agrobacterium-mediated or direct DNA transformation. Simultaneous
      expression of the luxA and luxB genes was monitored by protein immunoblot
      analysis. Luciferase-mediated light emission provided evidence for the assembly
      of the two protein subunits into a functional dimeric enzyme in plant
      protoplasts, in transformed calli, and in leaves of transformed plants. Bacterial
      luciferase may provide a useful marker-gene system for the quantitative assay of
      coordinate gene expression in transgenic plants.

PMID- 16593794
TI  - Reconstitution of chlorophyll a/b light-harvesting complexes: Xanthophyll
      dependent assembly and energy transfer.
AB  - A method for in vitro reconstitution of the chlorophyll a/b light-harvesting
      complex from LiDodSO(4)/heat-denatured or acetone-extracted photosynthetic
      membranes has been developed. Characterization of the minimum components
      necessary for the functional organization of pigments in these membrane complexes
      reveals that xanthophylls are essential structural components.

PMID- 16593795
TI  - "Cluster-ion" bombardment of biological macromolecules: Morphological evidence
      for disassembly of single tobacco mosaic virus particles.
AB  - Cluster ions containing 50, 100, or 200 water molecules and one proton are
      accelerated to over 275 kV and impacted on thin carbon films on which tobacco
      mosaic virus has been dispersed. After bombardment the films are examined with a
      transmission electron microscope to study induced morphological alterations with
      respect to the energy transfer processes that take place during and after single
      cluster-ion impact. Observations on tobacco mosaic virus indicate that a single
      cluster impact results in the removal of a cylindrical segment of the virus. No
      fragments from the excised TMV segment were observed on the carbon foil. We
      speculate that cluster-ion bombardment may become a useful analytical technique
      for structural studies of large biological macromolecular complexes.

PMID- 16593796
TI  - Regulation of a plant pathogenesis-related enzyme: Inhibition of chitinase and
      chitinase mRNA accumulation in cultured tobacco tissues by auxin and cytokinin.
AB  - Two endochitinases (EC 3.2.1.14) of M(r) values of approximately 34,000 and
      approximately 32,000 have been purified from cultured tissues of Nicotiana
      tabacum cv. Havana 425. The chitinase content of cloned tobacco pith tissues
      subcultured on hormone-free medium increases by approximately 5-fold to 8% of the
      soluble protein over a 7-day period. This induction is inhibited >90% by addition
      of combinations of the plant hormones auxin and cytokinin to the culture medium.
      Chitinase is also developmentally regulated in the intact plant. Not detectable
      in leaves near the top of the plant, it is 1-4% of the soluble protein in roots
      and lower leaves. A cDNA clone of tobacco chitinase was isolated containing a
      single, large open reading frame of 310 amino acids that includes the complete
      amino acid sequence of the mature enzyme. Chitinase and chitinase mRNA measured
      by RNA blot analysis show similar patterns of regulation indicating that
      chitinase accumulation is controlled, at least in part, at the mRNA level. The
      patterns were also similar to those obtained with glucan endo-1,3-beta
      glucosidase (EC 3.2.1.39) suggesting that the two enzymes are coordinately
      regulated.

PMID- 16593797
TI  - Differential mRNA transcription during salinity stress in barley.
AB  - The molecular and genetic bases of salinity tolerance in plants are not
      understood. Gene expression at the mRNA level was investigated in a salt-tolerant
      and a salt-sensitive genotype of barley. Seedlings were exposed to NaCl stress
      and translatable mRNAs were isolated from root and shoot tissues. A reticulocyte
      cell-free system was programed with barley mRNAs and the in vitro products were
      resolved on two-dimensional polyacrylamide gels following isoelectric focusing or
      nonequilibrium pH gradient gel electrophoresis in the first dimension. The
      functional mRNAs in unstressed seedlings were qualitatively almost
      indistinguishable in the two genotypes. However, salinity stress triggered
      differential transcription of specific mRNAs depending upon genotype and tissue.
      In roots, 12 new mRNAs were induced that encoded proteins of 21-34 kDa, with a pI
      range of 6.1-7.7. In shoots, the 9 new mRNAs coded for proteins of 18-50.5 kDa,
      with a pI range of 5.4-7.8. These new stress mRNAs represented one of two main
      classes. Class I consisted of mRNAs shared by both genotypes. Class II
      represented mRNAs specific to each genotype; unique mRNAs of roots accumulated
      preferentially in the salt-tolerant genotype, whereas those of shoots accumulated
      in the salt-sensitive genotype. The findings suggest that transcriptional as well
      as posttranscriptional mechanisms regulate gene expression in barley during
      salinity stress.

PMID- 16593798
TI  - Gene induction and repression by salt treatment in roots of the salinity
      sensitive Chinese Spring wheat and the salinity-tolerant Chinese Spring x
      Elytrigia elongata amphiploid.
AB  - An artificial amphiploid from a cross between salinity-sensitive bread wheat
      cultivar Chinese Spring and highly tolerant Elytrigia elongata (Host) Nevski (=
      Agropyron elongatum Host) shows enhanced salinity tolerance relative to Chinese
      Spring. Poly(A)(+) RNA was isolated from roots, expanding leaves, and old leaves
      from amphiploid and Chinese Spring plants prior to and after acclimation to high
      levels of NaCl in solution cultures. Two-dimensional gel electrophoresis of the
      in vitro translation products was used to compare these mRNA populations. The
      amphiploid had 10 mRNA species induced or enhanced and 8 species repressed in
      root tissue during acclimation to saline growth conditions. These 18 transcripts
      affected by salt treatment were also detected in wheat roots, but only 4 of these
      were similarly regulated. In Chinese Spring the acclimation to saline stress
      resulted in a marked change in the level of expression of 34 transcripts in root
      tissue; of these, 26 were detected in the amphiploid and only 6 were regulated as
      in the amphiploid. No differences were seen in gene expression between salt
      treated and control plants in leaves and meristematic crowns and unexpanded
      leaves of the amphiploid.

PMID- 16593799
TI  - Explanation of parity nonconservation.
AB  - Space inversion and other discrete symmetries are treated within the frame of a
      theory of fundamental forces based only on general considerations of causality,
      symmetry, and stability, without ad hoc differential equations. The basic space
      time M is the Einstein universe R(1) x S(3) as a causal (or conformal) rather
      than a pseudo-Riemannian manifold. Its connected symmetry group is then a 15
      parameter group G locally equivalent to SO(2, 4), while the isometry group K of
      the Einstein universe is a 7-parameter subgroup. Correlation with conventional
      relativistic theory is based on a canonical imbedding of Minkowski space M(0)
      into M, together with the unique extendability of all transformations of the
      scaling-extended Poincare group P from M(0) to global transformations on M. The
      fundamental fermion field F and boson field B are here restricted to be real and
      are fully invariant under G(e), where the superscript e denotes the inclusion of
      space and time inversions. The role of C on F is taken over by a real matrix
      having the eigenvalues +/-i, that commutes with G but anticommutes with space
      inversion. The spin space for B consists of the real linear transformations on
      that for F. There is a corresponding natural total Lagrangian that is both G(e)
      and O(2)-gauge invariant, the latter leading to lepton and baryon number
      conservation, and which is nonparametric except for scale. The Weyl and Maxwell
      equations are deduced, and compelling identifications made for neutrinos and the
      photon. The e and mu neutrino pairs occur in strikingly inequivalent positions in
      F, appearing symmetric only in the conventional relativistic limit R -->
      infinity, where R is the ( G-invariant) fundamental length interpretable as the
      radius of the space S(3). The photon occurs as the lowest member of a coherent
      subfamily of B that includes natural candidates for bare versions of the W and Z
      particles. In the relativistic limit the interaction Lagrangian becomes a sum
      over all elementary processes, one of which appears as quantum electrodynamics
      with Majorana-type electrons.

PMID- 16593800
TI  - Red light-induced formation of ubiquitin-phytochrome conjugates: Identification
      of possible intermediates of phytochrome degradation.
AB  - Phytochrome is the photoreceptor that controls red light-mediated morphogenesis
      in higher plants. It exists in two photointerconvertible forms, a red light
      absorbing form, Pr, and a far-red light-absorbing form, Pfr. Because
      photoconversion of Pr to Pfr by a brief light pulse decreases the in vivo half
      life of this chromoprotein by a factor of approximately 100, this system offers a
      unique way to modulate the turnover rate of a specific protein and hence study
      the mechanisms responsible for selective protein degradation. In etiolated oat
      [Avena sativa (L.)] seedlings, degradation of phytochrome as Pfr follows zero
      order kinetics as measured both spectrally and by ELISA, with 50% of Pfr lost in
      approximately 130 min at 27 degrees C. Immunoblot analysis of the destruction
      process with anti-oat phytochrome immunoglobulins reveals that degradation
      involves the loss of the 124-kDa phytochrome monomer and that proteolytic
      intermediates of apparent molecular mass lower than 124 kDa do not accumulate to
      detectable levels in vivo (<0.015% of total phytochrome). The latter observation
      suggests that proteolytic breakdown of the protein is extremely rapid. However, a
      series of polypeptides with higher apparent molecular mass and recognized by anti
      phytochrome immunoglobulins (principally 129 and 134 kDa) appears after
      photoconversion to Pfr. These polypeptides represent no more than a few percent
      of the total immunologically detectable phytochrome pool and have incremental
      differences in apparent molecular mass of 5 kDa. They appear within 5 min after
      Pfr formation, reach maximal levels between 90 and 180 min, and decline
      thereafter. These polypeptides and others of apparent molecular mass up to 160
      kDa are also detectable with immunoglobulins directed against either oat or human
      ubiquitin, indicating that they are ubiquitin-phytochrome conjugates. Since
      ubiquitin conjugation is involved in intracellular protein turnover and since
      formation and degradation of Pfr-ubiquitin conjugates coincide with the turnover
      of Pfr, these data suggest that the Pfr form of phytochrome is degraded via a
      ubiquitin-dependent proteolytic pathway.

PMID- 16593801
TI  - Phytochelatins, a class of heavy-metal-binding peptides from plants, are
      functionally analogous to metallothioneins.
AB  - Phytochelatins are a class of heavy-metal-binding peptides previously isolated
      from cell suspension cultures of several dicotyledonous and monocotyledonous
      plants. These peptides consist of repetitive gamma-glutamylcysteine units with a
      carboxyl-terminal glycine and range from 5 to 17 amino acids in length. In the
      present paper we show that all plants tested synthesized phytochelatins upon
      exposure to heavy metal ions. No evidence for the occurrence of metallothionein
      like proteins was found. All data so far obtained indicate that phytochelatins
      are involved in detoxification and homeostasis of heavy metals in plants and thus
      serve functions analogous to those of metallothioneins in animals and some fungi.
      Phytochelatins are induced by a wide range of metal anions and cations.
      Phytochelatin synthesis in suspension cultures was inhibited by buthionine
      sulfoximine, a specific inhibitor of gamma-glutamylcysteine synthetase (EC
      6.3.2.2). This finding and kinetic studies of phytochelatin induction point to a
      synthesis from glutathione or its precursor, gamma-glutamylcysteine, in a
      sequential manner, thereby generating the set of homologous peptides.

PMID- 16593802
TI  - Genes for the catabolism and synthesis of an opine-like compound in Rhizobium
      meliloti are closely linked and on the Sym plasmid.
AB  - In alfalfa nodules induced by Rhizobium meliloti strain L5-30 the compound L-3-O
      methyl-scyllo-inosamine (3-O-MSI) is synthesized. This compound is also
      catabolized specifically by this strain. Its biological properties are therefore
      similar to the Agrobacterium opines. To answer the question whether opine-like
      compounds ("Rhizopines") play a role in a plant symbiotic interaction, we
      isolated the genes for the catabolism of 3-O-MSI (moc genes) and for the
      induction of its synthesis in the nodule [mos gene(s)]. moc and mos genes were
      shown to be closely linked and located on the Sym plasmid of L5-30, suggesting
      that they have co-evolved and may be important in symbiosis. These genes have
      been cloned into a broad host-range vector that can be mobilized into other R.
      meliloti strains where they are expressed. The location of the mos genes in the
      bacteria extends the opine concept, initially developed for a plant pathological
      interaction, to a symbiotic one.

PMID- 16593803
TI  - Unusual cardioactive peptide (CCAP) from pericardial organs of the shore crab
      Carcinus maenas.
AB  - An unusual crustacean cardioactive peptide (CCAP) from the pericardial organs of
      the shore crab Carcinus maenas has been purified to homogeneity by a two-step
      reversed-phase HPLC procedure. Manual microsequencing using the 4-(N,N
      dimethylamino)azobenzene 4'-isothiocyanate/phenylisothiocyanate double-coupling
      technique and automated gas-phase sequencing of the oxidized peptide revealed
      that CCAP is a nonapeptide (M(r) 957) of the sequence Pro-Phe-[unk]Cys-Asn-Ala
      Phe-Thr-Gly-Cys-NH(2). We have confirmed the sequence by chemical synthesis of
      the C-terminally amidated and nonamidated forms of the peptide. The presence of
      the amide group was indicated by lack of susceptibility to carboxypeptidase A and
      Y treatment and was confirmed by the observation that the native CCAP comigrated
      with the amidated synthetic peptide on HPLC. Native and synthetic CCAP displayed
      high accelerating activity on a semi-isolated crab heart preparation, whereas the
      nonamidated synthetic peptide was of much lower potency. The effect of CCAP was
      both inoand chronotropic. The two pericardial organs of one animal yielded 30-40
      pmol of extractable CCAP. Its sequence does not resemble that of any known
      neuropeptide. However, a "mirror-image" similarity to vasopressin is conspicuous.

PMID- 16593804
TI  - On certain Hecke rings.
AB  - We examine rings that embed into the smash product of the group algebra of the
      Weyl group with the field of meromorphic functions on the Cartan subalgebra and
      are generated by elements that satisfy braid relations. We prove that every such
      ring is isomorphic to either the Hecke algebra, the nil Hecke ring, or the group
      algebra of the Weyl group.

PMID- 16593805
TI  - Improving the in vitro protein digestibility of sorghum with reducing agents.
AB  - We have shown in previous reports that cooked sorghum protein is less digestible
      than other cooked cereal proteins. The pepsin-indigestible proteins in sorghum
      were found to be mainly prolamin proteins. Cooking sorghum in the presence of 2
      mercaptoethanol increased protein digestibility (in vitro with pepsin or
      trypsin/chymotrypsin) to a level comparable with other cereals. At a
      concentration of 100 mM, other reducing agents (dithiothreitol, sodium bisulfite,
      and L-cysteine) were equally effective in improving sorghum digestibility. When
      maize was cooked in the presence of 2-mercaptoethanol, protein digestibility
      increased 5% compared to 25% for sorghum. Cooking barley, rice, and wheat with 2
      mercaptoethanol had no significant effect on protein digestibility. The addition
      of reducing agents appears to prevent the formation of protein polymers linked by
      disulfide bonds.

PMID- 16593806
TI  - Ecdysteroid biosynthesis and embryonic development are disturbed in insects
      (Locusta migratoria) reared on plant diet (Triticum sativum) with a selectively
      modified sterol profile.
AB  - Wheat seedlings germinating in the presence of the systemic fungicide
      fenpropimorph accumulate 9beta,19-cyclopropylsterols (95% of total sterols) in
      place of Delta(5)-sterols, which are normally produced in these plants. Adult
      females of the phytophagous insect Locusta migratoria show a dramatic decrease in
      their cholesterol content when reared on fenpropimorph-treated wheat. These
      females lay eggs with the ecdysteroid concentration reduced by up to 80% as
      compared to controls. Injection of fenpropimorph to the insects or feeding them
      on wheat coated with the fungicide (normal sterol composition) does not affect
      their sterol or ecdysteroid profiles; addition of cholesterol to fenpropimorph
      treated wheat prior to feeding restores normal ecdysteroid titers in the insects.
      The severe reduction of the ecdysteroid content in eggs laid by females reared on
      fenpropimorph-treated wheat is associated with a series of developmental arrests
      and/or abnormalities. The results show that the dietary 9beta,19
      cyclopropylsterols cannot be used by Locusta in place of Delta(5)-sterols for
      ecdysteroid biosynthesis. They suggest that the selective inhibition of specific
      enzymes in the sterol biosynthetic pathway of the plants can be used as a
      strategy to control insect development.

PMID- 16593807
TI  - Isolation, identification, and synthesis of 2-carboxyarabinitol 1-phosphate, a
      diurnal regulator of ribulose-bisphosphate carboxylase activity.
AB  - The diurnal change in activity of ribulose 1,5-bisphosphate (Rbu-1,5-P(2))
      carboxylase [3-phospho-D-glycerate carboxy-lyase (dimerizing); EC 4.1.1.39] of
      leaves of Phaseolus vulgaris is regulated (in part) by mechanisms that control
      the level of an endogenous inhibitor that binds tightly to the activated
      (carbamoylated) form of Rbu-1,5-P(2) carboxylase. This inhibitor was extracted
      from leaves and copurified with the Rbu-1,5-P(2) carboxylase of the leaves.
      Further purification by ion-exchange chromatography, adsorption to purified Rbu
      1,5-P(2) carboxylase, barium precipitation, and HPLC separation yielded a
      phosphorylated compound that was a strong inhibitor of Rbu-1,5-P(2) carboxylase.
      The compound was analyzed by GC/MS, (13)C NMR, and (1)H NMR and shown to be 2
      carboxyarabinitol 1-phosphate [(2-C-phosphohydroxymethyl)-D-ribonic acid].
      Verification of structure was obtained by comparison of the inhibitory activity
      of the isolated compound with that of 2-carboxy-D-arabinitol 1-phosphate
      synthesized in vitro. This compound (but not 2-carboxy-D-arabinitol 5-phosphate)
      inhibited Rbu-1,5-P(2) carboxylase in a way that was kinetically identical to
      that of the isolated, naturally occurring compound. The structure of the isolated
      compound differs from the Rbu-1,5-P(2) carboxylase transition-state analogue 2
      carboxyarabinitol 1,5-bisphosphate only by the lack of the C-5 phosphate group.
      This difference results in a higher binding constant for the monophosphate (K(d)
      = 32 nM) compared with the bisphosphate (K(d) < 10 pM). The less tightly bound
      compound acts in a light-dependent, reversible regulation of Rbu-1,5-P(2)
      carboxylase activity in vivo.

PMID- 16593808
TI  - Hormonal regulation of protein synthesis associated with salt tolerance in plant
      cells.
AB  - Cultured tobacco cells (Nicotiana tabacum L. cv. Wisconsin 38) synthesize a
      predominant 26-kDa protein upon exposure to abscisic acid (ABA). ABA also
      accelerates the rate of adaptation of unadapted cells to NaCl stress. The ABA
      induced 26-kDa protein is immunologically cross-reactive to, and produces a
      similar pattern of peptides after partial proteolysis as, the major 26-kDa
      protein associated with NaCl adaptation. Both have pI values of >8.2. The
      synthesis of the ABA-induced 26-kDa protein is transient unless the cells are
      simultaneously exposed to NaCl stress. There is an association between increased
      intracellular accumulation of ABA during cell growth and commencement of
      synthesis of the 26-kDa protein. ABA induces the synthesis of an immunologically
      cross-reactive 26-kDa protein in cultured cells of several plant species. In
      tobacco plants, synthesis of the 26-kDa protein could be detected in several
      tissues but the highest level of expression was seen in outer stem tissue. In
      root tissues, exogenous ABA greatly stimulated the synthesis of 26-kDa protein as
      compared to outer stem tissue and leaf. We suggest that ABA is involved in the
      normal induction of the synthesis of 26-kDa protein and that the presence of NaCl
      is necessary for the protein to accumulate.

PMID- 16593809
TI  - Wound-inducible expression of a potato inhibitor II-chloramphenicol
      acetyltransferase gene fusion in transgenic tobacco plants.
AB  - A potato inhibitor II gene (IIK) was isolated from a library of potato genes in
      lambda bacteriophage. An 8-kilobase-pair (kbp) insert was identified using a
      tomato inhibitor II cDNA as a hybridization probe, and a 2.6-kbp fragment
      containing the gene was subcloned into the plasmid pUC13 and characterized. The
      nucleotide sequence of the isolated gene exhibited 87% identity with the wound
      inducible tomato inhibitor II cDNA sequence. The amino acid sequence of inhibitor
      IIK, deduced from the potato gene, exhibited 84% identity with the tomato
      inhibitor II protein. A 1000-bp restriction fragment from the 5' flanking region
      of the gene was fused to the open reading frame of the chloramphenicol
      acetyltransferase (CAT) gene. This fusion was terminated in two ways: (i) with a
      terminator sequence from the potato inhibitor II gene and (ii) with a terminator
      from the 6b gene of Ti plasmid pTiA6. These chimeric genes were transferred into
      tobacco cells via a binary Ti vector system, and transgenic plants were
      regenerated. The CAT gene was expressed in leaves of transformed plants in
      response to wounding when fused with the inhibitor IIK promoter and terminator
      regions. The chimeric gene containing the 6b terminator did not express CAT in
      response to wounding. The wound-inducible expression of CAT activity was systemic
      and was induced in tissues distal to the wounded tissues. The time course of
      wound induction of CAT activity in transgenic tobacco leaves is similar to that
      found for wound-inducible inhibitor I and II mRNAs in tomato leaves. These
      results demonstrate that sequences necessary and sufficient for wound
      inducibility are present within approximately 1000 bp of the control regions of
      the inhibitor IIK genes and that wound-inducible components of tobacco leaf cells
      can regulate these sequences.

PMID- 16593810
TI  - Unusual structure of geranium chloroplast DNA: A triple-sized inverted repeat,
      extensive gene duplications, multiple inversions, and two repeat families.
AB  - Physical and gene mapping studies reveal that chloroplast DNA from geranium
      (Pelargonium hortorum) has sustained a number of extensive duplications and
      inversions, resulting in a genome arrangement radically unlike that of other
      plants. At 217 kilobases in size, the circular chromosome is about 50% larger
      than the typical land plant chloroplast genome and is by far the largest
      described to date, to our knowledge. Most of this extra size can be accounted for
      by a 76-kilobase inverted duplication, three times larger than the normal
      chloroplast DNA inverted repeat. This tripling has occurred primarily by
      spreading of the inverted repeat into regions that are single copy in all other
      chloroplast genomes. Consequently, 10 protein genes that are present only once in
      all other land plants are duplicated in geranium. At least six inversions,
      occurring in both the inverted repeat and large single-copy region, must be
      postulated to account for all of the gene order differences that distinguish the
      geranium genome from other chloroplast genomes. We report the existence in
      geranium of two families of short dispersed repeats and hypothesize that
      recombination between repeats may be the major cause of inversions in geranium
      chloroplast DNA.

PMID- 16593811
TI  - Constitutive and anaerobically induced DNase-I-hypersensitive sites in the 5'
      region of the maize Adh1 gene.
AB  - DNase-I-hypersensitive sites have been characterized in a plant gene, maize Adh1
      (which encodes alcohol dehydrogenase 1). It has been generally recognized in
      animal genes that the chromatin of the 5' flanking region can be characterized by
      the accessibility of its DNA to the nuclease DNase I (EC 3.1.21.1), indicating
      which areas in the promoter are "open" to nuclear factors. The 5' region of the
      maize Adh1 gene contains two distinct DNase-I-hypersensitive regions, one
      constitutively present from position -160 to -700 and one that is anaerobically
      induced from position -35 to -150. The constitutive region contains three major
      hypersensitive sites, one of which corresponds in part to a region of potential Z
      DNA. The induced hypersensitive region includes TATAA at -38 and CAAT at -100 as
      well as other potential regulatory sequences.

PMID- 16593812
TI  - On the lognormality of rain rate.
AB  - A stochastic regression model is used in modeling rain rate. Under some
      conditions on the model parameters, it is shown that rain rate is asymptotically
      lognormal. An application of the model to the GATE (global atmospheric research
      program, Atlantic tropical experiment) data shows a remarkable agreement between
      the assumed and estimated model parameters for rain rate averaged over
      sufficiently large area and a sampling interval of 15 min.

PMID- 16593813
TI  - Wave energy and intertidal productivity.
AB  - In the northeastern Pacific, intertidal zones of the most wave-beaten shores
      receive more energy from breaking waves than from the sun. Despite severe
      mortality from winter storms, communities at some wave-beaten sites produce an
      extraordinary quantity of dry matter per unit area of shore per year. At wave
      beaten sites of Tatoosh Island, WA, sea palms, Postelsia palmaeformis, can
      produce > 10 kg of dry matter, or 1.5 x 10(8) J, per m(2) in a good year.
      Extraordinarily productive organisms such as Postelsia are restricted to wave
      beaten sites. Intertidal organisms cannot transform wave energy into chemical
      energy, as photosynthetic plants transform solar energy, nor can intertidal
      organisms "harness" wave energy. Nonetheless, wave energy enhances the
      productivity of intertidal organisms. On exposed shores, waves increase the
      capacity of resident algae to acquire nutrients and use sunlight, augment the
      competitive ability of productive organisms, and protect intertidal residents by
      knocking away their enemies or preventing them from feeding.

PMID- 16593814
TI  - Rhizobium symbiotic genes required for nodulation of legume and nonlegume hosts.
AB  - Parasponia, a woody member of the elm family, is the only nonlegume genus whose
      members are known to form an effective nitrogen-fixing symbiosis with
      Bradyrhizobium or Rhizobium species. The Bradyrhizobium strain Rp501, isolated
      from Parasponia nodules, also nodulates the legumes siratro (Macroptilium
      atropurpureum) and cowpea (Vigna unguiculata). To test whether some of the same
      genes are involved in the early stages of legume and nonlegume nodulation, we
      generated transposon Tn5 insertions in the region of three evolutionarily
      conserved genes (nodA, nodB, and nodC) required for legume nodulation in several
      Rhizobium and Bradyrhizobium species. Assays of these mutant Rp501 strains on
      legume hosts and Parasponia seedlings established that nodABC are required for
      nodulation of legume and nonlegume hosts, indicating that nonlegumes and legumes
      can respond to the same bacterial signal(s). In addition, a strain carrying a Tn5
      insertion adjacent to the nodABC genes vigorously nodulated Rp501 legume hosts
      but was incapable of nodulating Parasponia, possibly identifying a nonlegume
      specific nodulation function.

PMID- 16593815
TI  - A Drosophila gene is subject to glucose repression.
AB  - Amylase-specific cDNA probes were used to assay amylase mRNA levels in third
      instar larvae of Drosophila melanogaster. It is shown that there is a difference,
      of the order of 100-fold, in the mRNA levels between larvae that are fed 10%
      glucose and larvae of the same wild-type strain that are fed an equivalent diet
      lacking glucose. In fact, the glucose-fed larvae have barely detectable levels of
      amylase mRNA. This large difference in transcript abundance indicates that the
      glucose effect, which we previously characterized at the level of enzyme
      activity, probably reflects a change in the transcriptional activity of the
      amylase gene.

PMID- 16593816
TI  - Algebraic complexities and algebraic curves over finite fields.
AB  - We consider the problem of minimal (multiplicative) complexity of polynomial
      multiplication and multiplication in finite extensions of fields. For infinite
      fields minimal complexities are known [Winograd, S. (1977) Math. Syst. Theory 10,
      169-180]. We prove lower and upper bounds on minimal complexities over finite
      fields, both linear in the number of inputs, using the relationship with linear
      coding theory and algebraic curves over finite fields.

PMID- 16593817
TI  - Labeling quinone-binding sites in photosynthetic reaction centers: A 38
      kilodalton protein associated with the acceptor side of photosystem II.
AB  - 2-Acetoxymethyl-1,4-naphthoquinone (2-AcOMeNQ) binds with rapid kinetics and high
      affinity to the primary quinone Q(A) site of reaction centers from
      Rhodopseudomonas capsulata. Binding of 2-AcOMeNQ fully restores electron-transfer
      activity with kinetics that is similar, but not identical, to that seen with
      ubiquinone-50. When bound at the Q(A) site, 2-AcOMeNQ preferentially labels the L
      subunit. This preference suggests that 2-AcOMeNQ labels primarily the region of a
      quinone-binding site that is close to the first isoprenoid unit of the side
      chain, which is expected from the location and structure of the reaction region
      of the molecule. In photosystem II particles from Synechococcus sp., 2-AcOMeNQ
      primarily labels two polypeptides with apparent molecular masses of 38 and 19
      kDa. Labeling of only the 38-kDa polypeptide is sufficiently sensitive to 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU) to conclude that it is involved in
      binding quinones on the acceptor side of photosystem II. Although we have not yet
      identified the 38-kDa protein, its properties suggest that it is the D2 protein.
      From the DCMU-sensitive labeling and from homologies to functionally important
      regions of the bacterial reaction-center subunits, we propose that the 38-kDa
      protein is intimately involved in binding the cofactors that mediate primary
      photochemistry.

PMID- 16593818
TI  - Cauliflower mosaic virus coat protein is phosphorylated in vitro by a virion
      associated protein kinase.
AB  - A protein kinase has been found to be associated with particles of the plant
      virus cauliflower mosaic virus. This protein kinase can phosphorylate endogenous
      viral capsid proteins in vitro and exchange substrates with casein kinase type
      II. The activity is not affected by cAMP but is enhanced considerably by ADP. The
      cofactor is either Mn(2+) or Mg(2+), and the phosphate donor is either ATP or
      GTP. Serine and threonine residues are phosphorylated.

PMID- 16593819
TI  - G protein and diacylglycerol regulate metamorphosis of planktonic molluscan
      larvae.
AB  - The regulatory guanine nucleotide binding protein (G protein) activators cholera
      toxin and the GTP analog 5-guanylyl imidophosphate, the second messenger
      diacylglycerol, and certain diamino acids all facilitate (amplify) the settlement
      and metamorphic responses of planktonic larvae of Haliotis rufescens (marine
      mollusc) to morphogenetic chemical stimuli. In contrast, the G protein-inhibiting
      analog guanosine 5'-O-[beta-thio]diphosphate inhibits facilitation by L
      alpha,beta-diaminopropionic acid but does not block facilitation by
      diacylglycerol. Diacylglycerol, cholera toxin, and the guanine nucleotide analogs
      alone neither induce the settlement and metamorphosis of the larvae nor do they
      inhibit induction of metamorphosis by gamma-aminobutyric acid. These results thus
      establish the existence of separate regulatory and inductive pathways controlling
      larval metamorphosis in response to two classes of exogenous chemical signals
      from the environment. The regulatory pathway, operating independently through a G
      protein-diacylglycerol cascade apparently controlled by facilitating diamino
      acids in the water column, can amplify the larval responsiveness to inducers of
      metamorphosis. This mechanism may have adaptive significance in the recognition
      and selection of favorable habitats for metamorphosis of the larvae. Similar
      regulatory pathways, based on exogenous control of a G protein-diacylglycerol
      cascade, may govern responsiveness to stimuli in other sensory and developmental
      systems.

PMID- 16593820
TI  - Virulence genes A, G, and D mediate the double-stranded border cleavage of T-DNA
      from the Agrobacterium Ti plasmid.
AB  - Agrobacterium tumefaciens transfers the T-DNA portion of its Ti plasmid to the
      nuclear genome of plant cells. Upon cocultivation of A. tumefaciens strain A348
      with regenerating tobacco leaf protoplasts, restriction endonuclease fragments of
      the T-DNA were generated that are consistent with double-stranded cleavage of the
      T-DNA at the border sequences. The T-DNA border cleavage was also induced by
      acetosyringone, a compound that induces many of the virulence genes. T-DNA
      cleavage did not occur in Agrobacterium strains harboring Tn3-HoHo1 insertions in
      the virA, -D, or -G genes. Insertion mutations in virB, -C, or -E did not have
      any effect on the T-DNA cleavage. Complementation of the mutations in virA, -D,
      or -G with cosmids containing the respective wild-type genes restored the T-DNA
      cleavage. Since virA and -G are essential in regulating the expression of other
      vir genes in response to plant signal molecules, the virD gene product(s) appear
      to mediate double-stranded T-DNA border cleavage.

PMID- 16593821
TI  - Chlorophyll catabolism in senescing plant tissues: In vivo breakdown
      intermediates suggest different degradative pathways for Citrus fruit and parsley
      leaves.
AB  - High-pressure liquid chromatography was used to separate chlorophyll derivatives
      in acetone extracts from senescing Citrus fruit peel, autumnal Melia azedarach L.
      leaves, and dark-held detached parsley (Petroselinum sativum L.) leaves.
      Chlorophyllide a and another polar, dephytylated derivative accumulated in large
      amounts in senescing Citrus peel, particularly in fruit treated with ethylene.
      Ethylene also induced a 4-fold increase in the specific activity of Citrus
      chlorophyllase (chlorophyll chlorophyllidohydrolase, EC 3.1.1.14). Detailed
      kinetics based on a hexane/acetone solvent partition system showed that the in
      vivo increase in dephytylated derivatives coincided with the decrease in total
      chlorophyll. Polar, dephytylated derivatives accumulated also in senescing Melia
      leaves. Senescing parsley leaves revealed a very different picture. The gradual
      disappearance of chlorophyll a was accompanied by an increase in pheophytin a and
      by the transient appearance of several phytylated derivatives. Only pheophytin a
      and an adjacent peak were left when all the chlorophyll a had disappeared. The
      pathways for breakdown of chlorophyll in the Citrus and parsley senescence
      systems are discussed.

PMID- 16593822
TI  - Cloning of genes developmentally regulated during plant embryogenesis.
AB  - Genes specifically induced during somatic embryogenesis may play key roles in
      plant embryo development. An antiserum against an extract of carrot somatic
      embryos revealed a few rare antigens induced at the onset of embryogenesis.
      Through differential immunoadsorption techniques, we purified antibodies against
      the embryo-specific antigens and probed a phage lambda gt11 library of cDNA from
      carrot somatic embryos. This paper describes three distinct cDNA clones that
      hybridize to embryo-specific RNAs. Monospecific antibodies, purified by affinity
      to the recombinant phage fusion proteins, confirm that the cloned cDNAs encode
      unique embryo-specific peptide antigens. One 50-kDa protein correlates with
      embryogenic ability in cultures of other plant species, including cereals.

PMID- 16593823
TI  - Asymptotically minimax stochastic search strategies in the plane.
AB  - Stochastic search strategies are proposed for finding a possibly mobile target
      within a convex region of the plane. The strategies are asymptotically minimax as
      epsilon --> 0 with respect to the time required to get within epsilon of the
      target.

PMID- 16593824
TI  - Extensive genetic divergence associated with speciation in filamentous fungi.
AB  - Little is known about genetic differentiation during speciation in fungi. The
      Collybia dryophila complex (Basidiomycetes: Tricholomataceae) contains several
      closely related groups of fungi at various levels of evolutionary divergence.
      Mating compatibility studies show there are several intersterile groups within
      the complex, three of which are distributed over two or more continents. Genetic
      relationships among five intersterility groups were compared by the method of
      DNA.DNA hybridization. Clustering techniques were used to reconstruct
      phylogenetic relationships of these fungi. Genic identity based on DNA.DNA
      hybridization corresponds well with mating compatibility. Reduced genic identity
      was observed between geographically isolated populations of a single mating
      group. This evidence suggests an allopatric mode of evolution for the C.
      dryophila group. These results indicate extensive genic divergence is associated
      with the appearance of intersterility barriers in basidiomycetous fungi. The
      levels of divergence observed in these and in other fungi are significantly
      higher than that observed in many other eukaryotes, and this suggests that the
      rate of molecular or morphological evolution in fungi may differ from that found
      in other organisms.

PMID- 16593825
TI  - Light induction of gene expression in Myxococcus xanthus.
AB  - The synthesis of carotenoids by Myxococcus xanthus requires illumination with
      blue light. Mutations at two loci (carA and carR) remove the blue-light
      requirement and cause constitutive production of carotenoids. Mutations at a
      different locus (carB) prevent carotenogenesis in both wild-type and constitutive
      mutant strains. We describe here three independent car mutations induced by
      insertion of Tn5 lac, a transposon that carries a transcriptional probe for
      exogenous promoters. All three transposon insertions block carotenogenesis even
      in constitutive mutant strains. One insertion is in a previously unknown car gene
      and the other two are in the carB locus. One of the carB insertions expresses
      beta-galactosidase at very low levels in the dark but is strongly activated by
      light. When this Tn5 lac insertion is introduced in carA or carR mutants it
      expresses beta-galactosidase in dark- as well as light-grown cells. We conclude
      that carotenogenesis in M. xanthus is activated at the level of transcription by
      a light-induced mechanism in which the carA and the carR loci (or their gene
      products) take part. The potential usefulness of M. xanthus as a simple and
      sensitive tool for studies in photobiology is discussed.

PMID- 16593826
TI  - Bacteriopheophytin g: Properties and some speculations on a possible primary role
      for bacteriochlorophylls b and g in the biosynthesis of chlorophylls.
AB  - Bacteriopheophytin g and small amounts of bacteriochlorophyll g have been
      obtained in high purity from the recently discovered photosynthetic bacterium
      Heliobacterium chlorum. Preparative methods and precautions in handling these
      sensitive compounds are described. The compounds have been characterized by
      californium-252 plasma desorption mass spectrometry, HPLC, visible absorption,
      and electron spin resonance spectroscopy. Our results agree with the structure of
      bacteriochlorophyll g advanced by H. Brockmann and A. Lipinski [(1983) Arch.
      Microbiol. 136, 17-19], with the exception that we find the esterifying alcohol
      to be farnesol and not geranylgeraniol as originally suggested. Zero field
      splitting parameters of triplet state bacteriopheophytin g and the ESR properties
      of the cation free radical of bacteriochlorophyll g are reported. The
      photoisomerization of the subject compounds has been studied. Bacteriopheophytin
      g undergoes photo-isomerization in white light to pheophytin a with a half-time
      of approximately 42 min. We suggest that all of the chlorophylls are
      biosynthesized from a common intermediate containing an ethylidine group, [unk]CH
      CH(3), such as is present in bacteriochlorophylls b and g.

PMID- 16593827
TI  - A chemical model for the cooperation of sulfates and carboxylates in calcite
      crystal nucleation: Relevance to biomineralization.
AB  - Acidic matrix macromolecules involved in regulation of biological crystal growth
      often contain aspartic acid-rich domains and covalently bound sulfated
      polysaccharides. We propose that sulfates and beta-sheet structured carboxylates
      cooperate in oriented calcite crystal nucleation. The sulfates concentrate
      calcium, creating the supersaturation necessary for nucleation on the structured
      carboxylate domains. An artificial model, composed of sulfonated polystyrene
      surfaces and adsorbed beta-sheet poly(aspartate), demonstrates that the two
      components indeed act cooperatively with respect to two independent assays, both
      by induction of calcite nucleation off the (001) plane and by calcium
      association. Evidence is presented that a purified organic matrix acidic
      glycoprotein from mollusk shells may behave in vitro in a similar way.

PMID- 16593828
TI  - Activities synthesizing and degrading fructose 2,6-bisphosphate in spinach leaves
      reside on different proteins.
AB  - Activities catalyzing the synthesis and degradation of fructose 2,6-bisphosphate
      6-phosphofructo-2-kinase (ATP:D-fructose-6-phosphate-2-phosphotransferase, EC
      2.7.1.105) and fructose-2,6-bisphosphatase (D-fructose-2,6-bisphosphate 2
      phosphohydrolase, EC 3.1.3.46)-were isolated from spinach leaves by an improved
      procedure and separated on the basis of both charge and molecular weight. The
      separated activities showed no detectable cross-contamination, indicating, in
      contrast to all previous data, that they are not present on a single bifunctional
      protein of the classical type in liver. The fructose-2,6-bisphosphatase-a newly
      discovered phosphatase enzyme-differed from previous mixed preparations by
      showing greater specificity but lower affinity for fructose 2,6-bisphosphate,
      greater sensitivity to inhibition by inorganic phosphate, and in being sensitive
      to inhibition by Mg(2+). The 6-phosphofructo-2-kinase was found to be inhibited
      by low levels of inorganic pyrophosphate and, in addition, to be regulated by the
      metabolites described previously. Similar results were obtained with preparations
      from lettuce leaves. The results support the view that, through individual
      regulation of the activities catalyzing its synthesis and breakdown, cytosolic
      metabolites are key factors in controlling the fructose 2,6-bisphosphate content
      of leaves.

PMID- 16593829
TI  - Rapid auxin-induced stimulation of cell wall synthesis in pea internodes.
AB  - The effect of auxin (indole-3-acetic acid; IAA) on growth and incorporation of
      myo-[2-(3)H(N)]inositol ([(3)H]Ins) into noncellulosic polysaccharides in the
      cell walls of third internode sections from red light-grown pea seedlings (Pisum
      sativum L. cv. Alaska) was investigated. Intact sections were incubated on
      [(3)H]Ins for 4 hr to permit uptake of the tracer and then IAA was added. Growth
      started after a lag phase of 15 min under these conditions. The sections were
      removed from the tracer and separated into epidermis and cortical cylinder
      (cortex plus vascular tissue). In the epidermis, IAA-induced stimulation of
      [(3)H]Ins incorporation started after a lag of 15 min. The amount of
      incorporation was 15% higher after 30 min and 24% higher after 2 hr than in the
      control. In the cortical cylinder, IAA-induced stimulation of [(3)H]Ins
      incorporation started only approximately 1 hr after adding IAA. The ionophore
      monensin (20 muM) inhibited the IAA-induced growth by 95%. Under these
      conditions, the IAA-induced stimulation of [(3)H]Ins incorporation and the IAA
      induced increase in in vivo extensibility of the sections was almost completely
      inhibited, although oxygen uptake was unaffected. We suggest that wall synthesis
      (as represented by [(3)H]Ins incorporation) and wall loosening (increase in in
      vivo extensibility) are related processes. The results support the hypothesis
      that IAA induces growth by rapid stimulation of cell wall synthesis in the growth
      limiting epidermal cell layer.

PMID- 16593830
TI  - Floral determination in internode tissues of day-neutral tobacco first occurs
      many nodes below the apex.
AB  - The temporal and spatial patterns of floral determination in cultured internode
      segments of Nicotiana tabacum L. cv. Wisconsin 38 were investigated. Segments
      from internodes, when cultured on hormone-free medium, either produced some de
      novo floral shoots or produced only vegetative shoots. Segments that produced
      some floral shoots were considered to contain florally determined tissues. The
      first internode tissues to exhibit floral determination were located 24 nodes
      (about 15 cm) below the terminal meristem on plants that had 21 leaves of length
      >/=3 cm (i.e., plants of age 21). Since the terminal meristem was morphologically
      vegetative at this age, floral determination in internode tissues did not result
      from a signal emanating from floral structures. As the plant continued growing,
      internode tissues progressively higher on the main axis gained the capacity to
      produce de novo floral shoots in culture. These data indicate that the inductive
      signal which elicited the state of floral determination in internode tissues was
      active in the upper half of the plant beginning at about age 21.

PMID- 16593831
TI  - Mutation to male fertility and toxin insensitivity in Texas (T)-cytoplasm maize
      is associated with a frameshift in a mitochondrial open reading frame.
AB  - Tissue culture-derived mutants of male-sterile and disease toxin-sensitive Texas
      (T)-cytoplasm maize that exhibit male fertility and toxin insensitivity carry
      numerous alterations in mitochondrial DNA. In these mutants, a 6.7-kilobase Xho I
      fragment characteristic of parental T cytoplasm has been rearranged. In the
      mutant T-4, the parental 6.7-kilobase Xho I fragment contains a guanine to
      adenine transition adjacent to a 5-base-pair insertion not found in T cytoplasm.
      The insertion, internal to a 345-base-pair open reading frame (T ORF13),
      generates a frameshift, resulting in a premature stop codon that terminates the
      open reading frame at base pair 222. In other mutants, the 345-base-pair ORF is
      part of a 3-kilobase deletion, which extends into a 5-kilobase repeat
      characteristic of mtDNA from T but not N male-fertile cytoplasm. Clones specific
      to T ORF13 hybridize to eight transcripts in T and T-4, yet only hybridize to
      three transcripts in T-7, a deletion mutant. Transcription of the T ORF13 region
      appears not to be altered in T-4, but the frameshift mutation in the T ORF13
      reading frame indicates that a biologically inactive gene product could be
      associated with the mutational events. The results suggest that cytoplasmic male
      sterility and disease toxin sensitivity may be associated with presence of T
      ORF13 in T-cytoplasm maize.

PMID- 16593832
TI  - Phytotoxins from the pathogenic fungi Drechslera maydis and Drechslera
      sorghicola.
AB  - Drechslera maydis, the causal agent of Southern corn leaf blight, and Drechslera
      sorghicola, the causal agent of leaf spot on Johnson grass, produce a series of
      phytotoxic sesterterpenoids. These sesterterpenoids belong to the ophiobolin
      family. One of them, ophiobolin I, was characterized by x-ray diffraction and
      served as a crucial reference compound for characterizing four other ophiobolins.
      All of the ophiobolins studied produce characteristic lesions on host plants at
      concentrations of 1 mM to 1 muM. The ophiobolin characterized as 6-epiophiobolin
      A is selectively toxic to corn bearing Texas-male-sterile (Tms) cytoplasm when
      assayed in a dark CO(2) fixation assay. It is plausible that these ophiobolins
      had a role in the 1970 corn-blight epidemic in North America.

PMID- 16593833
TI  - Discrete wave mechanics: Multidimensional systems.
AB  - Discrete wave mechanics is pursued further by extending the one-dimensional
      treatment to two (or more) dimensions in the light of explicit momentum
      considerations. Cognizance is taken of the effect of particle motion on mass and
      hence on the interactions between components of motion in different directions.
      The overall energy parameter turns out to be a product instead of a sum of
      parameters identified with each of several orthogonal axes. Accordingly, the
      separation of variables is most directly accomplished by factoring the principal
      energy parameter in conjunction with factoring the wave vector expression itself.
      Wave vector energies, on the other hand, remain additive. Finally, group velocity
      components are discussed for higher-dimensional systems.

PMID- 16593834
TI  - Algebraic K-theory of discrete subgroups of Lie groups.
AB  - Let G be a Lie group (with finitely many connected components) and Gamma be a
      discrete, cocompact, torsion-free subgroup of G. We rationally calculate the
      algebraic K-theory of the integral group ring ZGamma in terms of the homology of
      Gamma with trivial rational coefficients.

PMID- 16593835
TI  - Isolation of a cytochrome aa(3) gene from Bradyrhizobium japonicum.
AB  - Bradyhizobium japonicum strain LO501 is a Tn5-induced mutant that does not
      express the terminal oxidase cytochrome aa(3) (cytochrome-c oxidase, EC 1.9.3.1).
      Two and one-half kilobase pairs of LO501 genomic DNA that flanks the transposon
      was isolated and used as a hybridization probe to obtain the wild-type gene from
      a cosmid library. Two subcloned fragments from two of the isolated cosmids were
      ligated into broad host range vectors, and restriction maps of these fragments
      were generated. The resultant plasmids, pCA1 and pBL33, each contained DNA
      homologous to that mutated in strain LO501. The two plasmids were each introduced
      into strain LO501 by conjugal transfer, and it was found that pCA1, but not
      pBL33, complemented the oxidase mutant. The transconjugant strain LO501[pCA1]
      expressed wild-type levels of cytochrome aa(3), as discerned
      spectrophotometrically, and had restored N,N,N',N'-tetramethyl-p-phenylenediamine
      oxidase activity. Furthermore, the frequency of complementation of LO501 cells
      that received pCA1 by conjugation was 1.0, demonstrating that pCA1 complemented
      the mutant in trans. The results show that pCA1 contains the entire wild-type
      gene that was mutated in strain LO501, and this gene is required for cytochrome
      aa(3) expression.

PMID- 16593836
TI  - Gene tandem-mediated selection of coliphage lambda-receptive Agrobacterium,
      Pseudomonas, and Rhizobium strains.
AB  - Agrobacterium, Pseudomonas, and Rhizobium spp. have been made receptive to
      coliphage lambda. To achieve this, recombinant (pTROY) plasmids carrying a
      constitutive Escherichia coli lamB gene encoding the lambda receptor and
      expressed from an insertion sequence 3 (IS3) promoter were introduced into
      various bacteria. Because the wild-type lambda receptor was not expressed in
      these bacteria, a procedure called the lamB gene tandem protocol was used to
      select lamB alleles that expressed the lambda receptor. This gene tandem protocol
      may have general use in adapting genes with nonselectable traits to different
      organisms. Agrobacterium, Pseudomonas, and Rhizobium strains carrying pTROY41613,
      which encoded a gene tandem-selected lambda receptor, could be quantitatively
      transduced with lambda-packaged cosmids. With the ability to confer lambda
      receptivity on organisms, phage lambda now becomes a general DNA delivery agent.

PMID- 16593837
TI  - Crystal structure of hexagonal MnAl(4).
AB  - A structure is proposed for the hexagonal form of MnAl(4), with a(H) = 28.4 A and
      c(H) = 12.43 A, on the basis of a high-resolution electron micrograph and
      comparison with crystals of known structures. The proposed structure involves
      seven 104-atom complexes of 20 Friauf polyhedra, sharing some atoms with one
      another. It is closely related to the 23.36-A cubic structure of MnAl(4) and to
      the 14.19-A cubic structure of Mg(32)(Al,Zn)(49).

PMID- 16593838
TI  - Spatial separation of parental genomes in hybrids of somatic plant cells.
AB  - Chromosome spatial arrangements on metaphase plates of intergeneric intertribal
      cell hybrids of Nicotiana chinensis and Atropa belladonna as well as
      interspecific somatic hybrid plants of Nicotiana plumbaginifolia and Nicotiana
      sylvestris were analyzed. In the metaphases of the first divisions of protoplast
      fusion products, chromosomes of the two parents were spatially separated
      (segmented metaphase). In long-term cultured somatic hybrids, the topology of
      genome separation pattern in both callus cells and plants showed changes in form
      from "segmental" to "radial." Growing the hybrid cells in the presence of
      colchicine resulted in random chromosome arrangement both in cells directly
      exposed to different colchicine concentrations and in colchicine-treated cells
      grown in colchicine-free media. The degree of genome separation calculated for
      different cell clones remained constant during in vitro propagation of cells but
      was significantly lower for subclones derived from colchicine-treated cells.
      Therefore, it is concluded that spatial chromosome arrangement in metaphase is
      epigenetically controlled.

PMID- 16593839
TI  - Isolation and partial purification of an enzyme catalyzing the formation of O
      xylosylzeatin in Phaseolus vulgaris embryos.
AB  - An enzyme catalyzing the formation of a cytokinin metabolite, an O-pentosyl
      derivative of zeatin [Lee, Y. H., Mok, M. C., Mok, D. W. S., Griffin, D. A. &
      Shaw, G. (1985) Plant Physiol. 77, 635-641], was isolated from Phaseolus vulgaris
      embryos. Of all the potential pentose donors tested, UDP-xylose was the only
      substrate recognized by the enzyme. This indicates that the O-pentosyl
      derivatives previously obtained are O-xylosylzeatin and its ribonucleoside. The
      enzyme (UDP-xylose:zeatin O-xylosyltransferase, EC 2.4.2.-) has high affinity for
      trans-zeatin (K(m) 2 muM) and dihydrozeatin (K(m) 10 muM) but does not recognize
      cis-zeatin or ribosylzeatin. The molecular weight of the enzyme is approximately
      50,000 and the pH optimum of the reaction is 8-8.5. Under comparable isolation
      and reaction conditions, similar enzyme activity could not be detected in P.
      lunatus embryos, confirming the genetic differences observed in vivo.

PMID- 16593840
TI  - Ribosomal RNA-encoding DNA introgression across a narrow hybrid zone between two
      subspecies of grasshopper.
AB  - A ribosomal RNA-encoding DNA (rDNA) cloned sequence, consisting of a 0.8-kilobase
      fragment from the 26S/nontranscribed spacer region, was used to identify
      diagnostic restriction enzyme fragments that distinguish the Moreton and
      Torresian subspecies of the grasshopper Caledia captiva. These restriction
      fragments were then used to study patterns of rDNA variation across a narrow
      geographical hybrid zone between the two subspecies. The pattern of rDNA
      variation that emerged after the analysis of over 250 individuals clearly
      demonstrates the asymmetrical introgression of the Moreton ribosomal RNA genes
      into the Torresian subspecies. This asymmetric movement of genetic material
      occurs even though there exists extreme postmating F(2) and backcross inviability
      between the two subspecies. From our data, as well as those of previous
      chromosomal and allozymic studies, we are able to support the occurrence of
      nonrandom processes such as biased gene conversion and/or natural selection.
      Because the rDNA loci in the Moreton and Torresian individuals are located in
      different regions on chromosomes 10 and 11, it should be possible to determine
      the relative contributions of conversion, natural selection, and these sorts of
      processes to the pattern of introgression of the Moreton rDNA into the Torresian
      subspecies.

PMID- 16593841
TI  - Evidence from x-ray and neutron powder diffraction patterns that the so-called
      icosahedral and decagonal quasicrystals of MnAl(6) and other alloys are twinned
      cubic crystals.
AB  - It is shown that the x-ray powder diffraction patterns of rapidly quenched
      MnAl(6) and Mg(32)(Al,Zn)(49) and the neutron powder diffraction pattern of
      MnAl(6) are compatible with the proposed 820-atom primitive cubic structure
      [Pauling, L. (1987) Phys. Rev. Lett. 58, 365-368]. The values found for the edge
      of the unit cube are 23.365 A (x-ray) and 23.416 A (neutron) for MnAl(6) and
      24.313 A (x-ray) for Mg(32)(Al,Zn)(49).

PMID- 16593842
TI  - Characteristic classes, singular embeddings, and intersection homology.
AB  - This note announces some results on the relationship between global invariants
      and local topological structure. The first section gives a local-global formula
      for Pontrjagin classes or L-classes. The second section describes a corresponding
      decomposition theorem on the level of complexes of sheaves. A final section
      mentions some related aspects of "singular knot theory" and the study of
      nonisolated singularities. Analogous equivariant analogues, with local-global
      formulas for Atiyah-Singer classes and their relations to G-signatures, will be
      presented in a future paper.

PMID- 16593843
TI  - A topological concept of smallness.
AB  - We introduce a concept of smallness yielding topological spaces intuitively
      smaller than those that are simultaneously of universal measure zero and
      perfectly meager. Without any set-theoretic assumptions we show that there is a
      small uncountable algebraic subfield of the reals.

PMID- 16593844
TI  - Exact Hausdorff dimension in random recursive constructions.
AB  - The exact Hausdorff dimension function is determined for sets in R(m) constructed
      by using a recursion that is governed by some given law of randomness.

PMID- 16593845
TI  - Stable transformation of soybean by electroporation and root formation from
      transformed callus.
AB  - Soybean protoplasts from a number of commercially important cultivars have been
      genetically engineered by way of electroporation using chimeric genes coding for
      resistance to the aminoglycoside antibiotics kanamycin and G418. Effective
      electroporation conditions were determined by monitoring transient expression
      from aminoglycoside 3'-phosphotransferase II (APHII) expression plasmids.
      Electroporation of protoplasts with a chimeric APHII gene and subsequent
      selection on media supplemented with kanamycin resulted in the recovery of calli
      resistant to the antibiotic. Enzyme assays for APHII activity and Southern blot
      hybridization confirmed the expression of the foreign DNA and its stable
      integration into the soybean genome. Root formation was induced from transformed
      calli, and these roots maintained expression of the APHII gene.

PMID- 16593846
TI  - Mutational analysis of potato spindle tuber viroid reveals complex relationships
      between structure and infectivity.
AB  - Viroids are single-stranded, covalently closed circular RNA pathogens that can be
      isolated from certain higher plants afflicted with specific diseases. Their small
      size (246-375 nucleotides; M(r) 0.8-1.3 x 10(5)) and ability to replicate
      autonomously make viroids a unique model system in which to study the
      relationships between the structure of an RNA and its biological function. The
      demonstrated infectivity of certain cloned viroid cDNAs allows the use of site
      specific mutagenesis techniques to probe structure-function relationships
      suggested by comparative sequence analysis. Several site-specific mutations that
      disrupt base pairing in either the native structure or secondary hairpin I
      destroyed the ability of potato spindle tuber viroid cDNA to initiate infection.
      Alterations in the terminal loops of the native structure also abolished cDNA
      infectivity. One pseudorevertant, a mutant cDNA containing compensating changes
      that restore base pairing in the native structure, was marginally infectious; a
      second pseudorevertant in which base pairing was restored within the stem of
      secondary hairpin I was not infectious. The behavior of these mutants
      dramatically demonstrates the effect of remarkably small structural changes on
      viroid infectivity and emphasizes the importance of the conserved rod-like native
      structure for viroid function.

PMID- 16593847
TI  - Structure and expression of the genes, mcrBDCGA, which encode the subunits of
      component C of methyl coenzyme M reductase in Methanococcus vannielii.
AB  - The genes that encode the alpha, beta, and gamma subunits of component C of
      methyl coenzyme M reductase (mcrA, mcrB, and mcrG) in Methanococcus vannielii
      have been cloned and sequenced, and their expression in Escherichia coli has been
      demonstrated. These genes are organized into a five-gene cluster, mcrBDCGA, which
      contains two genes, designated mcrC and mcrD, with unknown functions. The mcr
      genes are separated by very short intergenic regions that contain multiple
      translation stop codons and strong ribosomebinding sequences. Although the genome
      of M. vannielii is 69 mol% A+T, there is a very strong preference in the mcrA,
      mcrB, and mcrG genes for the codon with a C in the wobble position in the codon
      pairs AA(U) (C) (asparagine), GA(U) (C) (aspartic acid), CA(U) (C) (histidine),
      AU(U) (C) (isoleucine), UU(U) (C) (phenylalanine), and UA(U) (C) (tyrosine). The
      mcrC and mcrD genes do not show this codon preference and frequently have U or A
      in the wobble position. As the codon pairs listed above are likely to be
      translated by the same tRNA with a G in the first anticodon position, the
      presence of C in the wobble position might ensure maximum efficiency of
      translation of transcripts of these very highly expressed genes.

PMID- 16593848
TI  - Bidirectional assembly of tobacco mosaic virus in vitro.
AB  - THE TIMING OF THE BIDIRECTIONAL GROWTH IN THE ASSEMBLY REACTION OF TOBACCO MOSAIC
      VIRUS HAS BEEN THE SUBJECT OF CONTROVERSY: Does elongation actually occur
      simultaneously to 5' and 3' ends or sequentially, first to the 5' end and then to
      the 3' end? To determine the timing of elongation toward the 3' end directly,
      using the S1 nuclease mapping method on a cloned cDNA with micrococcal nuclease
      digested tobacco mosaic virus RNA, we analyzed encapsidation of the RNA region
      that was located downstream from the assembly origin. The results clearly showed
      that elongation toward the 3' end did not occur for at least the first 4 min.
      Actually it was first observed at 8 min. It is concluded that, in the first 5-7
      min, a rapid elongation of the nucleation complex occurs only toward the 5' end
      of the RNA and that this gives rise to an intermediate particle 260 nm long.
      Furthermore, the lengths of the RNA that were protected against S1 nuclease
      digestion showed a clear banding pattern that had a spacing of approximately 100
      nucleotides. This supports the hypothesis that the 20S aggregate is kinetically
      favored as the protein source for elongation to the 3' end.

PMID- 16593849
TI  - Evidence for the involvement of more than one metal cation in the Schiff base
      deprotonation process during the photocycle of bacteriorhodopsin.
AB  - The removal of metal cations inhibits the deprotonation process of the protonated
      Schiff base during the photocycle of bacteriorhodopsin. To understand the nature
      of the involvement of these cations, a spectroscopic and kinetic study was
      carried out on bacteriorhodopsin samples in which the native Ca(2+) and Mg(2+)
      were replaced by Eu(3+), a luminescent cation. The decay of Eu(3+) emission in
      bacteriorhodopsin can be fitted to a minimum of three decay components, which are
      assigned to Eu(3+) emission from three different sites. This is supported by the
      response of the decay components to the presence of (2)H(2)O and to the changes
      in the Eu(3+)/bR molar ratio. The number of water molecules coordinated to Eu(3+)
      in each site is determined from the change in its emission lifetime when (2)H(2)O
      replaces H(2)O. Most of the emission originates from two "wet" sites of low
      crystal-field symmetry-e.g., surface sites. Protonated Schiff base deprotonation
      has no discernable effect on the emission decay of protein-bound Eu(3+),
      suggesting an indirect involvement of metal cations in the deprotonation process.
      Adding Eu(3+) to deionized bacteriorhodopsin increases the emission intensity of
      each Eu(3+) site linearly, but the extent of the deprotonation (and color)
      changes sigmoidally. This suggests that if only the emitting Eu(3+) ions cause
      the deprotonation and bacteriorhodopsin color change, ions in more than one site
      must be involved-e.g., by inducing protein conformation changes. The latter could
      allow deprotonation by the interaction between the protonated Schiff base and a
      positive field of cations either on the surface or within the protein.

PMID- 16593850
TI  - Alternative perspective on photosynthetic yield and enhancement.
AB  - In the traditional Z scheme of photosynthesis the Emerson effects of red drop
      (decline in yield of photosynthesis in far-red light) and enhancement (of far-red
      yield by supplementary short-wavelength light) are taken to be evidence for the
      coupling in series of two photosystems that absorb unsymmetrically in the far-red
      region of the spectrum. An alternative explanation for red drop and enhancement
      is proposed here that does not invoke the series-coupling hypothesis. It is
      suggested that the Emerson effects may be due to the drop in intensity of
      radiation from sample absorption, which causes a photochemical loss when the
      reaction shuts off at depth in the medium. The effects of oxygen, carbon dioxide,
      and temperature on the yield may also be interpreted in terms of this model.

PMID- 16593851
TI  - Voltage dependence of K channels in guard-cell protoplasts.
AB  - Stomatal pores in leaves enable plants to regulate the exchange of gases with
      their environment. Variations of the pore aperture are mediated by controlled
      changes of potassium salt concentrations in the surrounding guard cells. The
      voltage-dependent gating of K(+)-selective channels in the plasma membrane
      (plasmalemma) of cell-wall-free guard cells (protoplasts) was studied at the
      molecular level in order to investigate the regulation of K(+) fluxes during
      stomatal movements. Inward and outward K(+) currents across the plasmalemma of
      guard cells were identified by using the whole-cell configuration of the patch
      clamp technique. Depolarizations of the membrane potential from a holding
      potential of -60 mV to values more positive than -40 mV produced outward currents
      that were shown to be carried by K(+). Hyperpolarizations elicited inward K(+)
      currents. Inward and outward currents were selective for K(+) over Na(+) and
      could be partially blocked by exposure to extracellular Ba(2+). In cell-attached
      and excised membrane patches, previously identified K(+)-selective single
      channels in guard cells were studied. Averaging of single-channel currents during
      voltage pulses resulted in activation and deactivation kinetics that were similar
      to corresponding kinetics of inward and outward currents in whole cells, showing
      that K(+)-selective channels were the molecular pathways for the K(+) currents
      recorded across the plasmalemma of single guard-cell protoplasts. Estimates
      demonstrate that K(+) currents through the voltage-gated K(+) channels recorded
      in whole guard cells can account for physiological K(+) fluxes reported to occur
      during stomatal movements in leaves.

PMID- 16593852
TI  - Specific binding of a fungal glucan phytoalexin elicitor to membrane fractions
      from soybean Glycine max.
AB  - Treatment of soybean tissues with elicitors results in the production of
      phytoalexins, one of a number of inducible plant defense reactions against
      microbial infections. The present study uses a beta-1,3-[(3)H]glucan elicitor
      fraction from Phytophthora megasperma f. sp. glycinea, a fungal pathogen of
      soybean, to identify putative elicitor targets in soybean tissues. Use of the
      radiolabeled elicitor disclosed saturable high-affinity elicitor binding site(s)
      in membrane fractions of soybean roots. Highest binding activity is associated
      with a plasma membrane-enriched fraction. The apparent K(d) value for beta-glucan
      elicitor binding is approximately 0.2 x 10(-6) M and the maximum number of
      binding sites is 0.5 pmol per mg of protein. Competition studies with the
      [(3)H]glucan elicitor and a number of polysaccharides demonstrate that only
      polysaccharides of a branched beta-glucan type effectively displace the
      radiolabeled ligand from membrane binding. Differential displacing activity of
      the glucans on P. megasperma elicitor binding corresponds closely to their
      respective ability to elicit phytoalexin production in a cotyledon bioassay.

PMID- 16593853
TI  - Field tests of interspecific resource-based competition among phytoplankton.
AB  - The hypothesis that interspecific resource-based competition caused the spring
      and summer vertical segregation of phytoplankton species was tested in Lake Tahoe
      (California/Nevada). Two species (Cyclotella glomerata Bachmann and Synedra
      radians Kutz.) became dominant at different depth intervals (0-30 m and 60-90 m,
      respectively). Experimental transplants of assemblages between depths
      demonstrated asymmetrical competition. In the phosphate-limited region near the
      surface, growth of S. radians declined in the presence of C. glomerata. However,
      growth of C. glomerata was not affected by the presence of S. radians in the
      light-limited region at depth. This study provides field verification of resource
      based competition theory.

PMID- 16593854
TI  - Genetic transformation of the fungal pathogen responsible for rice blast disease.
AB  - The analysis of complex genetic determinants that control the ability of a fungus
      to colonize its host has been impaired by the lack of sophisticated genetic tools
      for characterizing important pathogens. We have developed a system for the
      genetic transformation of Magnaporthe grisea, the causal agent of rice blast
      disease, to overcome this limitation. A M. grisea arginine auxotroph was shown to
      contain a mutation (arg3-12) that abolishes ornithine carbamoyltransferase
      activity. M. grisea strains that contain arg3-12 were used as recipients in
      transformation experiments with plasmid pMA2, which carries the ArgB(+) gene from
      Aspergillus nidulans. Stable prototrophic transformants arose at a frequency of
      about 35 per microgram of plasmid DNA. Integration of single or multiple plasmid
      copies occurred at a single site in the genome of each transformant;
      rearrangements were often created during integration. When M. grisea genomic
      segments were incorporated into pMA2, the presence of any one of five different
      M. grisea segments did not greatly affect the efficiency of transformation.
      Integration via homologous recombination occurred when the donor plasmid was
      linearized by cleaving at a unique restriction site within the M. grisea segment.

PMID- 16593855
TI  - Nonreciprocal recombination between alleles of the chloroplast 23S rRNA gene in
      interspecific Chlamydomonas crosses.
AB  - The inheritance of six polymorphic loci mapping in the rRNA-encoding (rDNA)
      region of the inverted repeat sequence of chloroplast DNA (cpDNA) was scored in
      hybrid subclones derived from reciprocal interspecific crosses between the green
      algae Chlamydomonas eugametos and Chlamydomonas moewusii. In order to enhance the
      detection of cells that had undergone recombination between parental cpDNAs,
      hybrids were selected that inherited a chloroplast antibiotic-resistance marker
      contributed by the mating-type-minus(mt(-)) parent, the parent that normally
      contributes fewer cpDNA molecules. The major findings of this study can be
      summarized as follows. (i) The majority of the hybrids (14/17) were recombinant
      for cpDNA markers in the 10-kilobase-pair rDNA region under study. (ii) Only one
      allele of each polymorphic cpDNA locus was ever detected in the hybrids, thus
      suggesting that newly recombined rDNA sequences in one copy of the inverted
      repeat are rapidly spread to the other by a copy-correction mechanism. (iii)
      Chloroplast streptomycin-resistance (sr-2) and erythromycin-resistance (er-nM1)
      loci, although showing little or no genetic linkage, were mapped to the 16S and
      23S rRNA gene regions of the cpDNA, respectively, by virtue of their perfect
      coinheritance with polymorphic markers within these genes. (iv) cpDNA markers
      associated with a putative intron of the C. eugametos 23S rRNA gene were
      inherited by all 17 hybrids. Such a result is similar to that observed for
      certain alleles of the large rRNA gene of yeast mitochondria in crosses between
      omega(+) and omega(-) strains.

PMID- 16593856
TI  - T-equivariant K-theory of generalized flag varieties.
AB  - Let G be a Kac-Moody group with Borel subgroup B and compact maximal torus T.
      Analogous to Kostant and Kumar [Kostant, B. & Kumar, S. (1986) Proc. Natl. Acad.
      Sci. USA 83, 1543-1545], we define a certain ring Y, purely in terms of the Weyl
      group W (associated to G) and its action on T. By dualizing Y we get another ring
      Psi, which, we prove, is "canonically" isomorphic with the T-equivariant K-theory
      K(T)(G/B) of G/B. Now K(T)(G/B), apart from being an algebra over K(T)(pt.)
      approximately A(T), also has a Weyl group action and, moreover, K(T)(G/B) admits
      certain operators {D(w)}w[unk]W similar to the Demazure operators defined on
      A(T). We prove that these structures on K(T)(G/B) come naturally from the ring Y.
      By "evaluating" the A(T)-module Psi at 1, we recover K(G/B) together with the
      above-mentioned structures. We believe that many of the results of this paper are
      new in the finite case (i.e., G is a finite-dimensional semisimple group over C)
      as well.

PMID- 16593857
TI  - Characterization of cDNA for nodulin-75 of soybean: A gene product involved in
      early stages of root nodule development.
AB  - Establishment of a nitrogen-fixing root nodule is accompanied by a
      developmentally regulated expression of nodulin genes, only some of which, the so
      called early nodulin genes, are expressed in stages preceding actual nitrogen
      fixation. We have isolated soybean cDNA clones representing early nodulin genes
      and have studied clone pENOD2 in detail. The cDNA insert of this clone hybridizes
      to nodule-specific RNA of 1200 nucleotides in length. The RNA that was hybrid
      selected by the cloned ENOD2 DNA was in vitro translated to produce two nodulins
      with an apparent M(r) of 75,000, the N-75 nodulins. These two nodulins differ
      slightly in charge and one does not contain methionine. The amino acid sequence
      deduced from the DNA sequence shows that proline accounts for 45% of the 240
      residues in these nodulins and the sequence contains at least 20 repeating
      heptapeptide units. The amino acid composition of none of the (hydroxy)proline
      rich (glyco)proteins described in plants resembles the composition of the N-75
      nodulins, especially with respect to the high glutamic acid and the low serine
      content. This suggests that the N-75 nodulins belong to a hitherto unidentified
      class of presumably structural proteins. The genes encoding the N-75 nodulins
      were found to be expressed in nodule-like structures devoid of intracellular
      bacteria and infection threads, indicating that these nodulins do not function in
      the infection process but more likely function in nodule morphogenesis.

PMID- 16593858
TI  - K regulates bacteroid-associated functions of Bradyrhizobium.
AB  - Cowpea Bradyrhizobium 32H1 cells, when grown under 0.2% O(2), synthesize
      nitrogenase, as well as a methylammonium (ammonium) transport system and an
      electrogenic K(+)/H(+) antiporter. This effect was seen in growth medium
      containing 8-12 mM K(+) but not with 50 muM K(+). Addition of K(+) to cells
      growing under low O(2) tensions in low-K(+) medium led to various phenotypic
      properties associated with bacteroids, including the ability to reduce acetylene,
      induction of an ammonium transport carrier and the K(+)/H(+) antiporter, and
      increased synthesis of two heme-biosynthetic enzymes, delta-aminolevulinate
      synthase and delta-aminolevulinate dehydratase. K(+) addition caused the
      repression of glutamine synthetase and of capsular polysaccharide synthesis,
      functions related to the free-living state. A similar pattern of regulation was
      observed in Bradyrhizobium japonicum. In addition, K(+)-mediated depression in
      Bradyrhizobium 32H1 was inhibited by exudate of Vigna unguiculata, its host
      plant. We conclude that K(+) ions, in addition to low O(2) tension, are needed
      for the expression of several bacteroid-related functions in bradyrhizobia and
      thus are a major controlling influence in bacteroid development.

PMID- 16593859
TI  - Leaf assemblages across the Cretaceous-Tertiary boundary in the Raton Basin, New
      Mexico and Colorado.
AB  - Analyses of leaf megafossil and dispersed leaf cuticle assemblages indicate that
      major ecologic disruption and high rates of extinction occurred in plant
      communities at the Cretaceous-Tertiary boundary in the Raton Basin. In diversity
      increase, the early Paleocene vegetational sequence mimics normal short-term
      ecologic succession, but on a far longer time scale. No difference can be
      detected between latest Cretaceous and early Paleocene temperatures, but
      precipitation markedly increased at the boundary. Higher survival rate of
      deciduous versus evergreen taxa supports occurrence of a brief cold interval (<1
      year), as predicted in models of an "impact winter."

PMID- 16593860
TI  - Plant defense genes are regulated by ethylene.
AB  - One of the earliest detectable events during plant-pathogen interaction is a
      rapid increase in ethylene biosynthesis. This gaseous plant stress hormone may be
      a signal for plants to activate defense mechanisms against invading pathogens
      such as bacteria, fungi, and viruses. The effect of ethylene on four plant genes
      involved in three separate plant defense response pathways was examined; these
      included (i and ii) genes that encode L-phenylalanine ammonia-lyase (EC 4.3.1.5)
      and 4-coumarate:CoA ligase [4-coumarate:CoA ligase (AMP-forming), EC 6.2.1.12],
      enzymes of the phenylpropanoid pathway, (iii) the gene encoding chalcone
      synthase, an enzyme of the flavonoid glycoside pathway, and (iv) the genes
      encoding hydroxyproline-rich glycoprotein, a major protein component(s) of plant
      cell walls. Blot hybridization analysis of mRNA from ethylene-treated carrot
      roots reveals marked increases in the levels of phenylalanine ammonia-lyase mRNA,
      4-coumarate CoA ligase mRNA, chalcone synthase mRNA, and certain hydroxyproline
      rich glycoprotein transcripts. The effect of ethylene on hydroxyproline-rich
      glycoprotein mRNA accumulation was different from that of wounding. Ethylene
      induces two hydroxyproline-rich glycoprotein mRNAs (1.8 and 4.0 kilobases),
      whereas wounding of carrot root leads to accumulation of an additional
      hydroxyproline-rich mRNA (1.5 kilobases). These results indicate that at least
      two distinct signals, ethylene and a wound signal, can affect the expression of
      plant defense-response genes.

PMID- 16593861
TI  - Combined proton NMR imaging and spectral analysis of locust embryonic
      development.
AB  - Images and spectra of desert locust [Schistocerca gregaria (Forskal)] embryos
      were collected in vivo using a 4.7-tesla proton ((1)H) NMR imaging spectrometer.
      The 100 x 100 x 500 mum image resolution and 125-nl localized spectral volumes
      were obtained within minutes of each other. The dynamics of embryonic development
      were slow enough that the time delay between imaging and spectral measurements is
      negligible. Thus, image and spectral data correspond closely and approximate real
      time observations of embryonic changes. The above procedure was applied every 12
      hr during the entire course of development. This analytical approach demonstrates
      that imaging and localized spectroscopy can be used to visualize and assess
      changes in embryonic water and lipid content in concert with the development of a
      living embryo.

PMID- 16593862
TI  - T-DNA organization in tumor cultures and transgenic plants of the monocotyledon
      Asparagus officinalis.
AB  - Asparagus officinalis was the first monocotyledonous plant from which hormone
      independent and opine-producing crown gall tissue could be isolated. We confirm
      by DNA hybridization that tumor lines obtained after infection of this plant by
      Agrobacterium strains harboring wild-type nopaline and octopine tumor-inducing
      (Ti) plasmids are stably transformed and contain transferred DNA (T-DNA) segments
      identical to the T-DNA found in dicotyledonous plants. We have also infected
      Asparagus with a nononcogenic T-DNA vector that carries a chimeric aminoglycoside
      phosphotransferase [NOS-APH(3')II] gene and selected transformed tissues on
      kanamycin-containing medium. The transformed status of these tissues was then
      confirmed by DNA hybridization. From these calli we regenerated kanamycin
      resistant shoots that were subsequently rooted. Thus we report the isolation of
      transgenic monocotyledonous plants engineered via the Agrobacterium vector
      system.

PMID- 16593863
TI  - A mitochondrial protein associated with cytoplasmic male sterility in the T
      cytoplasm of maize.
AB  - Mitochondrial DNA in the T male-sterile cytoplasm (cms-T) of maize contains an
      open reading frame (ORF 13) associated with the T type of sterility. Antibodies
      raised to a chemically synthesized oligopeptide corresponding to ORF 13 were used
      to establish the expression of a 13-kDa protein from this reading frame. The 13
      kDa polypeptide is synthesized uniquely in cms-T maize and purifies with the
      membrane fraction of T mitochondria. We assign the symbol urf13-T to designate
      this mitochondrial gene. Presence of the nuclear restorer gene Rf1 in cms-T
      plants results in a decrease in abundance of 13-kDa protein and alteration in the
      transcripts of urf13-T.

PMID- 16593864
TI  - Behavioral feeding specialization in Pinaroloxias inornata, the "Darwin's Finch"
      of Cocos Island, Costa Rica.
AB  - As a population, Cocos Finches exhibit a broad range of feeding behaviors
      spanning those of several families of birds on the mainland, while individuals
      feed as specialists year-round. Although this extreme intraspecific variability
      occurs as predicted in a tropical oceanic island environment, these
      specializations challenge contemporary ecological theory in that they are not
      attributable to individual differences in age, sex, gross morphology, or
      opportunistic exploitation of patchy resources. Instead, they appear to originate
      and be maintained behaviorally, possibly via observational learning. This
      phenomenon adds another direction to the evolutionary radiation of the Darwin's
      Finches and underscores the necessity for detailed behavioral and ecological
      studies at the individual level for understanding animal feeding systems and the
      causation of phenotypic variation.

PMID- 16593865
TI  - Simulation of photochemical hole-burning experiments on photosynthetic reaction
      centers.
AB  - An effective Hamiltonian formalism is used to calculate the homogeneous linewidth
      of long-wavelength absorption in the photosynthetic reaction center. Agreement
      with the experimental values of approximately 400 cm(-1) for the hole width of
      the 990-nm band of Rhodopseudomonas viridis is obtained. The anomalously (two
      orders of magnitude) large width is explained in terms of resonant coupling to
      charge transfer states. These results support a dynamical model of primary charge
      separation [Friesner, R. & Wertheimer, R. (1982) Proc. Natl. Acad. Sci USA 79,
      2138-2142] in which such resonant coupling was also concluded to be important.

PMID- 16593866
TI  - L(2)-cohomology of arithmetic varieties.
AB  - The L(2)-cohomology of arithmetic quotients of bounded symmetric domains is
      studied. We establish the conjecture of Zucker equating the L(2)-cohomology of
      these spaces to the intersection cohomology of their Baily-Borel
      compactifications.

PMID- 16593867
TI  - Phytoalexin synthesis by the sorghum mesocotyl in response to infection by
      pathogenic and nonpathogenic fungi.
AB  - Infection of the sorghum mesocotyl by Helminthosporium maydis (a nonpathogen) and
      Colletotrichum graminicola (a pathogen) resulted in the rapid accumulation of a
      pigment complex by two sorghum cultivars. The components of the complex were
      fungitoxic. The principal compounds have been identified as the 3
      deoxyanthocyanidins apigeninidin and luteolinidin. Apigeninidin accumulated in
      both sorghum cultivars in response to infection and was the predominant pigment.
      Luteolinidin accumulated in only one of the cultivars. Because of the speed of
      synthesis, occurrence only in response to inoculation, and fungitoxicity of the
      individual components, we propose that synthesis of the pigment complex
      constitutes a defense response and that the compounds apigeninidin and
      luteolinidin should be considered as phytoalexins.

PMID- 16593868
TI  - Self-assembly of proglycinin and hybrid proglycinin synthesized in vitro from
      cDNA.
AB  - An in vitro system was developed that results in the self-assembly of subunit
      precursors into complexes that resemble those found naturally in the endoplasmic
      reticulum. Subunits of glycinin, the predominant seed protein of soybeans, were
      synthesized from modified cDNAs using a combination of the SP6 transcription and
      the rabbit reticulocyte translation systems. Subunits produced from plasmid
      constructions that encoded either Gy4 or Gy5 gene products, but modified such
      that their signal sequences were absent, self-assembled into trimers equivalent
      in size to those precursors found in the endoplasmic reticulum. In contrast,
      proteins synthesized in vitro from Gy4 constructs failed to self-assemble when
      the signal sequence was left intact (e.g., preproglycinin) or when the coding
      sequence was modified to remove 27 amino acids from an internal hydrophobic
      region, which is highly conserved among the glycinin subunits. Various hybrid
      subunits were also produced by trading portions of Gy4 and Gy5 cDNAs and all self
      assembled in our system. The in vitro assembly system provides an opportunity to
      study the self-assembly of precursors and to probe for regions important for
      assembly. It will also be helpful in attempts to engineer beneficial nutritional
      changes into this important food protein.

PMID- 16593869
TI  - Identification of an essential upstream element in the nopaline synthase promoter
      by stable and transient assays.
AB  - We studied the fine structure of the nopaline synthase (nos) promoter, which is
      active constitutively in a wide range of plant tissues, by both transient and
      stable transformation expression analyses. 3' and 5' deletion fragments were
      linked to form a set of internal deletion and duplication mutants that scanned
      the nos promoter. These mutated promoters were linked to the gene for the marker
      chloramphenicol acetyltransferase (CATase) as a means to readily assay promoter
      strength. The stable transformation analysis revealed the functional importance
      of an extended CCAAT box region (-97 to -63). Deletion of an upstream region (
      112 to -101) containing an octameric repeated element resulted in a reduction in
      promoter strength by a factor of 30. A further deletion (-119 to -101) disrupted
      a potential Z-DNA-forming element as well, totally eliminating promoter function.
      Thus, a 19-base deletion across a repeated octamer and a potential Z-DNA-forming
      element identifies an essential upstream activator in the nos promoter.
      Duplication of the upstream element tripled promoter activity. Electroporation
      mediated transient analysis was unable to distinguish downstream promoter
      elements. However, the upstream element behaved similarly in both assays in that
      deletion of the entire upstream element resulted in no promoter activity and that
      duplication of the element significantly enhanced the promoter strength.

PMID- 16593870
TI  - Expression of a complete soybean leghemoglobin gene in root nodules of transgenic
      Lotus corniculatus.
AB  - The complete soybean leghemoglobin lbc(3) gene was transferred into the legume
      Lotus corniculatus using an Agrobacterium rhizogenes vector system. Organ
      specific expression of the soybean gene was observed in root nodules formed on
      regenerated transgenic plants after infection with Rhizobium loti. The primary
      transcript was processed in the same way as in soybean nodules and the resulting
      mRNA was translated into Lbc(3) protein. Quantitative determination of the Lbc(3)
      protein in nodules of transgenic plants indicated that the steady-state level of
      the soybean protein is comparable to that of endogenous Lotus leghemoglobin.

PMID- 16593871
TI  - A chloroplast DNA inversion marks an ancient evolutionary split in the sunflower
      family (Asteraceae).
AB  - We determined the distribution of a chloroplast DNA inversion among 80 species
      representing 16 tribes of the Asteraceae and 10 putatively related families.
      Filter hybridizations using cloned chloroplast DNA restriction fragments of
      lettuce and petunia revealed that this 22-kilobase-pair inversion is shared by 57
      genera, representing all tribes of the Asteraceae, but is absent from the
      subtribe Barnadesiinae of the tribe Mutisieae, as well as from all families
      allied to the Asteraceae. The inversion thus defines an ancient evolutionary
      split within the family and suggests that the Barnadesiinae represents the most
      primitive lineage in the Asteraceae. These results also indicate that the tribe
      Mutisieae is not monophyletic, since any common ancestor to its four subtribes is
      also shared by other tribes in the family. This is the most extensive survey of
      the systematic distribution of an organelle DNA rearrangement and demonstrates
      the potential of such mutations for resolving phylogenetic relationships at
      higher taxonomic levels.

PMID- 16593872
TI  - Self-excitation of a nonlinear scalar field in a random medium.
AB  - We discuss the evolution in time of a scalar field under the influence of a
      random potential and diffusion. The cases of a short-correlation in time and of
      stationary potentials are considered. In a linear approximation and for
      sufficiently weak diffusion, the statistical moments of the field grow
      exponentially in time at growth rates that progressively increase with the order
      of the moment; this indicates the intermittent nature of the field. Nonlinearity
      halts this growth and in some cases can destroy the intermittency. However, in
      many nonlinear situations the intermittency is preserved: high, persistent peaks
      of the field exist against the background of a smooth field distribution. These
      widely spaced peaks may make a major contribution to the average characteristics
      of the field.

PMID- 16593873
TI  - The local redshift-distance relation and spatial uniformity.
AB  - Regrettably, the review of the redshift-distance relation in the review by
      Salpeter and Hoffman [Salpeter, E. E. & Hoffman, G. L., Jr. (1986) Proc. Natl.
      Acad. Sci. USA 83, 3056-3063], appears flawed. In particular, the logically
      inconclusive and uncertain hypothesis of local extragalactic spatial uniformity
      is used in an essential way. Moreover, even in conjunction with this hypothesis,
      the Lundmark law fits more closely than the Hubble law, on the basis of the data
      and criteria of Salpeter and Hoffman, when a rough approximation involved in the
      estimation of the galaxy luminosity function is eliminated. Specifically, the
      assumption that all galaxies in the redshift range 500-1700 km.s(-1) are
      effectively at the redshift 1100 km.s(-1) is made; when this assumption is
      replaced by a statistically optimal procedure that uses the precise redshifts,
      the relative fit of the two laws is reversed.

PMID- 16593874
TI  - Continuous partition lattice.
AB  - A continuous analogue to the partition lattices is presented. This is the metric
      completion of the direct limit of a system of embeddings of the finite partition
      lattices. The construction is analogous to von Neumann's construction of a
      continuous geometry over a field F from the finite-dimensional projective
      geometries over F.

PMID- 16593875
TI  - Transposon mutagenesis and tagging of fluorescent Pseudomonas: Antimycotic
      production is necessary for control of Dutch elm disease.
AB  - Antimycotic-producing strains of Pseudomonas syringae are being tested as Dutch
      elm disease control agents. We examined the role of antimycotic production in
      disease control. Transposon Tn903 was used to mutagenize the antimycotic
      producing strain MSU174. Eighty-one mutants that did not inhibit fungal growth
      were identified among 15,000 Tn903-containing derivatives. Linkages between Tn903
      insertions and defects in antimycotic metabolism were established. Three Tn903
      containing strains (two antimycotic producers and one nonproducer) were
      individually introduced into American elm seedlings. The seedlings were
      subsequently challenged with Ceratocystis ulmi, the causal agent of Dutch elm
      disease. Protection of the elms was observed with the two antimycotic-producing
      strains but not with the nonproducing strain. The introduced strains could be
      readily recovered from the seedlings after two growing seasons. They were
      unequivocally identified by the Tn903 insertions they contain.

PMID- 16593876
TI  - On the possibility of dust condensation in the ejecta of supernova 1987a.
AB  - We suggest that supernova 1987a may condense dust of substantial visual optical
      thickness as do many novae. The dust will act as a calorimeter of the photon
      luminosity of any central engine that is dominant at the time of dust formation.
      Observations of novae suggest that dust formation may occur when the expanding
      ejecta reach a temperature of 1000 K. The early luminosity of the supernova may
      be dominated by radioactivity that is unrelated to the central engine that
      determines the energy balance for the long-term development of the supernova. We
      discuss the possibility that a constant luminosity central power source such as a
      pulsar dominates the luminosity of the supernova ejecta by the time that dust can
      condense and argue that, if a shell mass of more than a few tenths of one solar
      mass was ejected, emission from dust may be observable in the thermal infrared
      spectral region. Maximum dust optical depth should occur by late 1987 or early
      1988. If the dust becomes optically thick, the visual light from the supernova
      may drop precipitously. The characteristics of an optically thick dust shell as a
      calorimeter of the luminosity of the central engine are discussed and are related
      to previous observations of dust formation in type II supernovae. It is suggested
      that dust of several chemical compositions may form at different epochs.

PMID- 16593877
TI  - In vitro synthesis of cellulose II from a cytoplasmic membrane fraction of
      Acetobacter xylinum.
AB  - The cytoplasmic and outer membranes of Acetobacter xylinum (ATCC 53582) were
      isolated by discontinuous sucrose density ultracentrifugation. Both lysozyme (EC
      3.2.1.17) and trypsin (EC 3.4.21.4) were required for efficient crude membrane
      separation. Primary dehydrogenases and NADH oxidase were used as cytoplasmic
      membrane markers, and 2-keto-3-deoxyoctulosonic acid was used to identify the
      outer membranes. Cellulose synthetase (UDP-glucose:1,4-beta-D-glucan 4-beta-D
      glucosyltransferase; EC 2.4.1.12) activity was assayed as the conversion of
      radioactivity from UDP-[(14)C]glucose into an alkali-insoluble beta-1,4-D
      [(14)C]glucan. This activity was predominantly found in the cytoplasmic membrane.
      The cellulose nature of the product was demonstrated by (i) enzymatic hydrolysis
      followed by TLC, (ii) methylation analysis followed by TLC, and (iii) GC/MS.
      Further, the weight-average and number-average degree of polymerization of the in
      vitro product, determined by high-performance gel permeation chromatography, were
      4820 and 5270, respectively. In addition, x-ray diffraction analysis indicated
      that the in vitro product is cellulose II, which is in contrast to the in vivo
      product-namely, cellulose I.

PMID- 16593878
TI  - Molecular cloning and characterization of the insecticidal crystal protein gene
      of Bacillus thuringiensis var. tenebrionis.
AB  - The insecticidal crystal protein gene of the coleopteran-toxic Bacillus
      thuringiensis var. tenebrionis has been isolated, and the nucleotide sequence has
      been determined. A total DNA library from var. tenebrionis was made in the
      plasmid vector pUC12. By using a synthetic 27-base oligonucleotide corresponding
      to a stretch of nine N-terminal amino acids of a tryptic fragment of purified
      crystal protein of var. tenebrionis as a probe, recombinant colonies were
      screened by in situ hybridization for the presence of the crystal protein gene.
      Positive clones obtained from this screening were further tested for toxicity.
      One recombinant, NSBP544 (which contained a 5.9-kilobase BamHI insert), was toxic
      to larvae of Colorado potato beetle. Immunoblot analysis revealed that this clone
      produces two crystal-specific antigens of 65 and 73 kDa as do sporulating var.
      tenebrionis cells. However, purified crystal inclusions from var. tenebrionis
      contain a primary peptide component of 65 kDa. A 1932-base-pair open reading
      frame with a coding capacity of 73,119 Da has been identified by nucleotide
      sequencing analysis of the cloned crystal protein. In addition, mung bean
      nuclease mapping indicates that transcription of the crystal protein of var.
      tenebrionis initiates 130 base pairs upstream from the translational start site.
      Southern blot analysis using an internal 0.7-kilobase EcoRI fragment of pNSBP544
      as a probe revealed that the crystal protein gene is located on a 90-MDa plasmid.

PMID- 16593879
TI  - Site-directed mutagenesis of the nitrogenase MoFe protein of Azotobacter
      vinelandii.
AB  - A strategy has been formulated for the site-directed mutagenesis of the
      Azotobacter vinelandii nifDK genes. These genes encode the alpha and beta
      subunits of the MoFe protein of nitrogenase, respectively. Six mutant strains,
      which produce MoFe proteins altered in their alpha subunit by known single amino
      acid substitutions, have been produced. Three of these transversion mutations
      involve cysteine-to-serine changes (at residues 154, 183, and 275), two involve
      glutamine-to-glutamic acid changes (at residues 151 and 191), and one involves an
      aspartic acid-to-glutamic acid change (at residue 161). All three possible
      phenotypic responses are observed within this group- i.e., normal, slow, and no
      growth in the absence of a fixed-nitrogen source. Two-dimensional gel
      electrophoresis indicates that all mutants accumulate normal levels of the
      subunits of both nitrogenase component proteins. Whole-cell and crude-extract
      acetylene-reduction activities indicate substantial levels of Fe protein activity
      in all strains. In contrast, MoFe protein activities do not parallel the
      diazotrophic growth capability for all strains. Two strains appear to exhibit
      altered substrate discrimination. Such analyses should aid in the identification
      of metallocluster-binding sites and subunit-subunit interaction domains of the
      MoFe protein and also provide insight into the mechanistic roles of the various
      prosthetic groups in catalysis.

PMID- 16593880
TI  - Light-stimulated inositolphospholipid turnover in Samanea saman leaf pulvini.
AB  - Leaflets of Samanea saman open and close rhythmically, driven by an endogenous
      circadian clock. Light has a rapid, direct effect on the movements and also
      rephases the rhythm. We investigated whether light signals might be mediated by
      increased inositolphospholipid turnover, a mechanism for signal transduction that
      is widely utilized in animal systems. Samanea motor organs (pulvini) labeled with
      [(3)H]inositol were irradiated briefly (5-30 sec) with white light, and membrane
      localized phosphatidylinositol phosphates and their aqueous breakdown products,
      the inositol phosphates, were examined. After a 15-sec or longer light pulse,
      labeled phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5
      bisphosphate decreased and their labeled metabolic products inositol 1,4
      bisphosphate and inositol 1,4,5-trisphosphate increased, changes characteristic
      of inositolphospholipid turnover. We conclude that inositolphospholipid turnover
      may act as a phototransduction mechanism in Samanea pulvini in a manner that is
      similar to that reported in animal systems.

PMID- 16593882
TI  - Temperature dependence and evolutionary adjustment of critical night length in
      insect photoperiodism.
AB  - The photoperiodic responses of Drosophila auraria are shown to involve its
      circadian system functioning as the "clock" that measures the duration of
      darkness at night. Attempts at further clarification of this finding were based
      on the widely held assumption that adaptive adjustment of critical night length
      is caused by change in the circadian system's entrainment behavior. Three
      different experimental programs yielded data that are incompatible with this
      starting premise. Collectively, the observations suggest a new interpretation of
      the lability (phenotypic and genetic) of critical night length based on change in
      the level of response to all night-length measurements-not on the measurements
      themselves. This proposition is found especially relevant to the temperature
      dependence of photoperiodic responses and its role in controlling the onset and
      termination of the breeding season at different latitudes.

PMID- 16593881
TI  - Complete tracking of transient proton flow through active chloroplast ATP
      synthase.
AB  - Proton pumping in thylakoid membranes and backflow of protons through the active
      ATP synthase CF0-CF1 (where CF0 is the proton channel and CF1 is the catalytic
      portion) were investigated by flash spectrophotometry. A steady pH difference
      across the membrane was generated by continuous measuring light, supplemented by
      voltage transients that were generated by flashing light. In the presence of P(i)
      and ADP, the electric potential transients elicited transients of proton flow via
      CF0-CF1, typically 1.3 H(+) per CF1 and flash group. Proton flow was blocked by
      CF0-CF1 inhibitors: N,N'-dicyclohexylcarbodiimide, acting on the channel
      component CF0, and tentoxin, acting on the catalytic component CF1. The half-rise
      time was 40 ms in (1)H(2)O and 78 ms in (2)H(2)O. ATP synthesis under conditions
      of flashing light and transient proton flow was characterized by a K(m)(P(i)) of
      only 14 muM, contrasting with a K(m) of several hundred micromolar for continuous
      ATP synthesis at high rate. This might reflect a resistance to P(i) diffusion.
      The degree of proton delocalization in the chemiosmotic coupling between redox
      reactions and ATP synthesis is under debate. In thylakoids, it has been proposed
      that intramembrane proton buffering domains act as ducts for protons between
      pumps and ATP synthases. In this work, transient proton flow by way of CF0-CF1
      was completely tracked from the lumen, across the membrane, and into the
      suspending medium. Proton uptake from the lumen and charge flow across the
      membrane occurred synchronously and in stoichiometric proportion. The uptake of
      protons from the lumen by CF0-CF1, half completed in 40 ms, was preceded by
      release of protons from water oxidation into the lumen, half completed in <1 ms.
      Hence, pumps and ATP synthases were coupled through the lumen without involvement
      of intramembrane domains.

PMID- 16593883
TI  - Abrupt transitions in physics and biophysics: van der Waals revisited.
AB  - An iteration procedure that relates pressure and volume changes in the
      condensation of a gas by means of two independent relations of the volume and the
      effective pressure predicts abrupt volume transitions similar to those
      experimentally observed. Similar abrupt transitions are predicted for a molecular
      association in which the association free energy is dependent upon the extent of
      reaction. The pressure, or the concentration, at which the abrupt transition
      occurs depends upon the volume, or the extent of reaction, used to initiate the
      iteration procedure and selection of the transition that corresponds to the
      equilibrium requires additional conditions. For the gas condensation, assumption
      of the symmetry of the effects of the pressure fluctuations at equilibrium gives
      results that coincide with those obtained by application of the Maxwell rule.
      From these observations it is concluded that abrupt transitions arise naturally
      when independent conditions cannot be simultaneously satisfied.

PMID- 16593884
TI  - Induction of Bradyrhizobium japonicum common nod genes by isoflavones isolated
      from Glycine max.
AB  - The early events in legume nodulation by Rhizobium spp. involve a conserved gene
      cluster known as the common nod region. A broad-host-range plasmid (pEA2-21)
      containing a Bradyrhizobium japonicum nodDABC-lacZ translational fusion was
      constructed and used to monitor nod gene expression in response to soybean root
      extract. Two inducing compounds were isolated and identified. Analysis using
      ultraviolet absorption spectra, proton nuclear magnetic resonance, and mass
      spectrometry showed that the two inducers were 4',7-dihydroxyisoflavone
      (daidzein) and 4',5,7-trihydroxyisoflavone (genistein). Induction was also seen
      with some, but not all, of the flavonoid compounds that induce nod genes in fast
      growing Rhizobium strains that nodulate clover, alfalfa, or peas. When pEA2-21
      was introduced into Rhizobium trifolii, it was inducible by flavones but not by
      daidzein and genistein. In Rhizobium fredii, pEA2-21 was induced by isoflavones
      and flavones. Thus, the specificity of induction appears to be influenced by the
      host-strain genome.

PMID- 16593885
TI  - Molecular cloning of complementary DNA encoding the lignin-forming peroxidase
      from tobacco: Molecular analysis and tissue-specific expression.
AB  - Plant peroxidases play a major role in lignin formation and wound healing and are
      believed to be involved in auxin catabolism and defense to pathogen attack. The
      function of the anionic peroxidase isozymes is best understood in tobacco. These
      isozymes catalyze the formation of the lignin polymer and form rigid cross-links
      between lignin, cellulose, and extensin in the secondary plant cell wall. We
      report the purification of the anionic peroxidase isozymes from tobacco and their
      partial amino acid sequence. An oligonucleotide probe deduced from the amino acid
      sequence was used to screen a tobacco leaf cDNA library and a 1200-base-pair cDNA
      clone was isolated and sequenced in its entirety. The predicted amino acid
      sequence revealed a 22-amino acid signal peptide and a 302-amino acid mature
      protein (M(r), 32,311). The amino acid sequence was compared to that of the
      cationic peroxidases from horseradish and turnip and was found to be 52% and 46%
      homologous, respectively. By RNA blot analysis, the messenger for the tobacco
      isozyme was found to be abundant in stem tissue while expressed at very low
      levels in leaf and root tissue. Four distinguishable copies of the gene were
      found on genomic DNA blots. The gene copy number may reflect the allotetraploid
      nature of Nicotiana tabacum.

PMID- 16593886
TI  - Sex pheromone production and perception in European corn borer moths is
      determined by both autosomal and sex-linked genes.
AB  - Inheritance patterns for sex pheromone production in females, pheromone detection
      on male antennal olfactory receptor cells, and male pheromone behavioral
      responses were studied in pheromonally distinct populations of European corn
      borers from New York State. Gas chromatographic analyses of pheromone glands,
      single sensillum recordings, and flight tunnel behavioral analyses were carried
      out on progeny from reciprocal crosses, as well as on progeny from subsequent
      F(2) and maternal and paternal backcrosses. The data show that the production of
      the female pheromone blend primarily is controlled by a single autosomal factor,
      that pheromone-responding olfactory cells are controlled by another autosomal
      factor, and that behavioral response to pheromone is controlled by a sex-linked
      gene. F(1) males were found to possess olfactory receptor cells that give spike
      amplitudes to the two pheromone isomers that are intermediate to those of the
      high and low amplitude cells of the parent populations. Fifty-five percent of the
      F(1) males tested responded fully to pheromone sources ranging from the hybrid
      (E)-11-tetradecenyl acetate/(Z)-11-tetradecenyl acetate (E/Z) molar blend of
      65:35 to the E/Z molar blend of 3:97 for the Z morph parents, but very few
      responded to the E/Z molar blend of 99:1 for the E morph parents. Data on the
      inheritance patterns support speculation that the Z morph is the ancestral and
      that the E morph is the derived European corn borer population.

PMID- 16593887
TI  - Atypical mitochondrial DNA from the deep-sea scallop Placopecten magellanicus.
AB  - The mitochondrial DNA of most metazoan animals is highly conserved in size,
      averaging about 17 kilobase paris (kbp). The mitochondrial DNA from the deep-sea
      scallop Placopecten magellanicus, in contrast, has been found to be approximately
      34 kbp long. It is also highly variable in size from individual to individual and
      is unusual in the extent of its size variation. Mitochondrial DNAs from
      individuals collected at the same site differ by as much as 7 kbp. The size
      variation is due largely to differences in the number of copies of a tandemly
      repeated 1.2-kbp element.

PMID- 16593888
TI  - Repressor of P elements in Drosophila melanogaster: Cytotype determination by a
      defective P element carrying only open reading frames 0 through 2.
AB  - The P element is a type of transposable element in Drosophila melanogaster.
      Characteristics of the syndrome of "hybrid dysgenesis" are due to transposition
      of P elements, and the molecular mechanism for regulation of this transposition
      has been unknown. In this study a Q strain (which carries only defective P
      elements in its genome but still is able to repress the transposition of complete
      P elements although defective in transposase activity) was used to determine the
      structure of the P element with this repressor (or P cytotype-determining)
      domain. Examination of the cytotype and structure of the P elements of particular
      strains with reduced copy number of P elements showed that the P element with a
      repressor domain was defective, being deleted between bases 1991 and 2448. This
      region corresponds to most of the third intron [between open reading frame (ORF)
      2 and ORF 3] as well as half the ORF 3 of an intact P element. Therefore ORF 3
      was deemed to be unnecessary for repressor production.

PMID- 16593889
TI  - Reduction, the trace formula, and semiclassical asymptotics.
AB  - We state a theorem that relates the theory of dimensional reduction in
      Hamiltonian mechanics to the spectral properties of elliptic operators with
      symmetries on compact manifolds. As an application, we show that the spectrum of
      the Schrodinger operator, -[unk]hDelta + V, as [unk]h --> 0, contains geometric
      information about the closed trajectories of a classical particle with
      Hamiltonian p(2) + V(q). More generally, we show that this is true for particles
      with internal degrees of freedom and subject to an external Yang-Mills field, the
      classical limit being the Wong-Sternberg-Weinstein system for such particles.

PMID- 16593890
TI  - S2 episome of maize mitochondria encodes a 130-kilodalton protein found in male
      sterile and fertile plants.
AB  - The mitochondrial genome of the S-type male-sterile cytoplasm of maize contains
      two linear episomes, S1 (6397 base pairs) and S2 (5453 base pairs). The S2
      episome contains two large unidentified open reading frames, URF1 (3512 base
      pairs) and URF2 (1017 base pairs). We have demonstrated that a polypeptide with
      an apparent molecular mass of 130 kDa is the gene product of URF1. This
      polypeptide was first detected in Coomassie blue-stained protein gels of cms-S
      (where cms = cytoplasmic male sterile) but not in those of cms-T, cms-C, or
      normal mitochondrial proteins. The protein product of a translational fusion
      containing the 5' end of Escherichia coli lacZ and an internal segment from URF1
      of S2 was recognized by antisera raised against the 130-kDa variant polypeptide.
      The mitochondria of fertile F(1) hybrids of cms-S x Ky21 (the male parent
      carrying nuclear fertility restoration genes) contain as much of the 130-kDa
      protein as is found in cms-S mitochondria of sterile plants. Spontaneous fertile
      cytoplasmic revertants from cms-S in a WF9 nuclear background also synthesized
      the 130-kDa polypeptide. Therefore, the mere presence or absence of the URF1 gene
      product of S2 does not determine the fertility status of maize plants, because
      male sterile and male fertile (nuclear restored and revertant) plants can contain
      equivalent amounts of the 130-kDa polypeptide.

PMID- 16593891
TI  - Sources of propionate for the biogenesis of ethyl-branched insect juvenile
      hormones: Role of isoleucine and valine.
AB  - Corpora allata from adult female Manduca sexta biosynthesize the sesquiterpenoid
      juvenile hormone (JH) III and the unusual ethyl-branched homologue JH II in
      vitro. We maintained corpora allata in medium 199 using [methyl-(3)H]methionine
      as the source of the JH methyl ester moiety and as a mass marker. This allowed
      measurement of the relative contributions of (14)C-labeled precursors to the
      biogenesis of JH II and III carbon skeletons. We showed efficient incorporation
      of a propionate equivalent, from isoleucine or valine catabolism, into the ethyl
      branched portion of JH II, using double-label liquid scintillation counting of
      isolated JHs and gas chromatography/mass spectrometry with selected ion
      monitoring of JH deuteromethoxyhydrin derivatives. Methionine was a poor source
      of propionate for JH II biosynthesis, while glucose, succinate, threonine, and
      beta-alanine did not contribute propionate at all. Leucine, isoleucine, and
      glucose incorporated into JH III and the acetate-derived portion of JH II.

PMID- 16593892
TI  - Lignin degradation by peroxidase in organic media: A reassessment.
AB  - The effect of horseradish peroxidase/H(2)O(2) in organic medium (dioxane/aqueous
      buffer, pH 5, 95:5) on the depolymerization of synthetic (dehydrogenatively
      polymerized) lignin was reinvestigated. In contrast to previous claims [Dordick,
      J. S., Marletta, M. A. & Klibanov, A. M. (1986) Proc. Natl. Acad. Sci. USA 83,
      6255-6257], our results demonstrated that vigorous depolymerization of this
      substrate did not occur. Further, during this treatment ferulic acid was not a
      significant biodegradation product.

PMID- 16593893
TI  - Analysis of cis-active sequences involved in the leaf-specific expression of a
      potato gene in transgenic plants.
AB  - ST-LS1 is a light-inducible, single-copy gene from potato that is expressed only
      in photosynthetic tissues. Various sequences derived from the 5'-upstream region
      of this gene were fused to the coding region of the chloramphenicol
      acetyltransferase (CAT) gene and to the gene 7 termination region of the transfer
      DNA (T-DNA) from the Agrobacterium Ti plasmid pTiACH5 and transferred to tobacco
      using Ti-plasmid vectors. After regeneration of whole plants, tissues were
      assayed for the expression of the CAT gene. Sequences derived from the 5'
      upstream region of the ST-LS1 gene comprising positions -334 to +11 were
      sufficient to confer a leaf/stem-specific as well as a light-inducible expression
      of the CAT gene. Destruction of chloroplasts by treatment with the herbicide
      norfluorazon and subsequent exposure to light drastically reduced the expression
      of the CAT gene indicating that this upstream sequence most likely interacts with
      a chloroplast-dependent signal. When sequences from position -98 to position +675
      were fused to a truncated inactive fragment of the cauliflower mosaic virus 35S
      promoter in a head-to-head manner, the corresponding chimeric genes were again
      expressed in photosynthetic tissues only, indicating that these sequences have
      enhancer-like properties.

PMID- 16593894
TI  - Leaf pubescence in buttonwood: Community variation in a putative defense against
      defoliation.
AB  - Plants have a variety of putative defenses against defoliation by herbivores,
      among which are pubescent leaves. Buttonwood (Conocarpus erectus), a Caribbean
      tree, shows considerable between-individual variation in this trait, and
      pubescent leaves have less herbivore damage. Surveying 97 island communities, I
      documented three patterns expected were pubescent individuals more frequent where
      herbivory is great. (i) Larger islands have a higher percentage of pubescence
      (larger islands have more herbivores). (ii) Islands nearer to a mainland have a
      higher percentage of pubescence (nearer islands receive more herbivore
      immigrants). (iii) Islands having an extremely abundant predator on foliage
      arthropods, arboreal lizards, have a smaller percentage of pubescence than no
      lizard islands. The third effect, though statistically significant, is weak
      relative to the direct effects of lizards on one category of their prey (spiders)
      measured in the same system.

PMID- 16593895
TI  - Selective inhibition of interleukin 2 gene function following thymocyte
      antigen/major histocompatibility complex receptor crosslinking: Possible thymic
      selection mechanism.

PMID- 16593896
TI  - Surface site diffusion and reaction on molecular "organizates" and colloidal
      catalysts: A geometrical perspective.
AB  - We study surface-mediated, diffusion-controlled reactive processes on particles
      whose overall geometry is homeomorphic to a sphere. Rather than assuming that a
      coreactant can diffuse freely over the surface of the particle to a target site
      (reaction center), we consider the case where the coreactant can migrate only
      among N - 1 satellite sites that are networked to the reaction site by means of a
      number of pathways or reaction channels. Five distinct lattice topologies are
      considered and we study the reaction efficiency both for the case where the
      satellite sites are passive and for the case where reaction may occur with finite
      probability at these sites. The results obtained for this class of surface
      problems are compared with those obtained by assuming that the reaction-diffusion
      process takes place on a planar, two-dimensional surface (lattice). The
      applicability of our results to surface-mediated processes on "organizates"
      (cells, vesicles, micelles) and on colloidally dispersed catalyst particles is
      brought out in the Introduction, and the correspondence between the lattice
      based, Markovian approach developed here and Fickian models of surface diffusion,
      particularly with regard to the exponentiality of the decay, is discussed in the
      concluding section.

PMID- 16593897
TI  - Selecting the highest of three binomial probabilities.
AB  - A sequential elimination procedure for selecting the highest probability in
      binomial trials, proposed by Levin and Robbins [Levin, B. & Robbins, H. (1981)
      Proc. Natl. Acad. Sci. USA 78, 4663-4666], is examined further in the special
      case of trials involving three probabilities. A conjectured inequality relating
      ratios of selection probabilities to odds ratios is shown to hold only under
      certain necessary and sufficient conditions. Weaker conjectured inequalities
      involving the probability of correct selection are shown to hold without
      restriction.

PMID- 16593898
TI  - Identification of the alternative terminal oxidase of higher plant mitochondria.
AB  - In addition to cytochrome oxidase, plant mitochondria have a second terminal
      oxidase called the alternative oxidase. The alternative oxidase is of great
      interest in that energy is not conserved when electrons flow through it. The
      potential energy of the system is thus lost as heat, and, in plants with high
      levels of the alternative oxidase, this results in thermogenesis. We have
      purified the alternative oxidase from mitochondria of the thermogenic spadix of
      Sauromatum guttatum and have identified its polypeptide constituents by using
      polyclonal antibodies. A 166-fold purification was achieved through a combination
      of cation-exchange (carboxymethyl-Sepharose) and hydrophobic-interaction (phenyl
      Sepharose) chromatography. Polyclonal antibodies raised to the CM-Sepharose
      fractions readily immunoprecipitated alternative oxidase activity and
      immunoprecipitated four of the proteins that copurify with the activity. These
      proteins have apparent molecular masses of 37, 36, 35.5, and 35 kDa. Polyclonal
      antibodies raised individually to the 37-, 36-, and 35.5- plus 35-kDa proteins
      cross-reacted with all of these proteins, indicating the presence of common
      antigenic sites. The 37-kDa protein appears to be constitutive in Sauromatum,
      whereas expression of the 36- and 35-kDa proteins was correlated with presence of
      alternative pathway activity. The 35.5-kDa protein appears with loss of
      alternative pathway activity during senescence, indicating that this protein may
      be a degradation product of the 36-kDa protein. Binding of anti-36-kDa protein
      antibodies to total mitochondrial protein blots of five plant species indicated
      that similar proteins were always present when alternative pathway activity was
      observed.

PMID- 16593899
TI  - Picosecond kinetics of fluorescence and absorbance changes in photosystem II
      particles excited at low photon density.
AB  - Oxygen-evolving photosystem II particles (from Synechococcus) with about 80
      chlorophyll molecules per primary electron donor (P(680)) were used for a
      correlated study of picosecond kinetics of fluorescence and absorbance changes,
      detected by the single-photon-timing technique and by a pump-probe apparatus,
      respectively. Chlorophyll fluorescence decays were biexponential with lifetimes
      tau(1) = 80 +/- 20 ps and tau(2) = 520 +/- 120 ps in open reaction centers and
      tau(1) = 220 +/- 30 ps and tau(2) = 1.3 +/- 0.15 ns in closed reaction centers.
      The corresponding fluorescence yield ratio F(max)/F(o) was 3-4. Absorbance
      changes were monitored in the spectral range of 620-700 nm after excitation at
      675 nm with 10-ps pulses sufficiently weak (<7 x 10(12) photons/cm(2) per pulse)
      to avoid singlet-singlet annihilation. With open reaction centers, the absorbance
      changes could be fit to the sum of three exponentials. The associated absorbance
      difference spectra were attributed to (i) exciton trapping and charge separation
      (tau = 100 +/- 20 ps), (ii) the electron-transfer step P(680) (+) I(-) Q(A) -->
      P(680) (+) I Q(A) (-) (where I is the primary electron acceptor and Q(A) is the
      first quinone acceptor) (tau = 510 +/- 50 ps), and (iii) the reduction of P(680)
      (+) by the intact donor side (tau > 10 ns). With closed reaction centers, the
      absorbance changes were biexponential with lifetimes tau(1) = 170-260 ps and
      tau(2) = 1.6-1.75 ns. The results are explained in terms of a kinetic model that
      assumes P(680) to constitute a shallow trap. The results show that Q(A) reduction
      in these photosystem II particles decreases both the apparent rate and the yield
      of the primary charge separation by a factor of 2-3 and increases the mean
      lifetime of excitons in the antenna by a factor of 3-4. Thus, we conclude that
      the long-lived, nanosecond chlorophyll fluorescence is not charge-recombination
      luminescence but rather emission from equilibrated excited states of antenna
      chlorophylls.

PMID- 16593900
TI  - Protonophores induce plastoquinol oxidation and quench chloroplast fluorescence:
      Evidence for a cyclic, proton-conducting pathway in oxygenic photosynthesis.
AB  - The photosynthetic apparatus converts light into chemical energy by a series of
      reactions that give rise to a coupled flow of electrons and protons that generate
      reducing power and ATP, respectively. A key intermediate in these reactions is
      plastoquinone (PQ), the most abundant electron and proton (hydrogen) carrier in
      photosynthetic membranes (thylakoids). PQ ultimately transfers electrons to a
      terminal electron acceptor by way of the Rieske Fe-S center of the cytochrome bf
      complex. In the absence of a terminal acceptor, electrons accumulate in the PQ
      pool, which is reduced to plastoquinol (PQH(2)), and also on a specialized PQ,
      Q(A), which is reduced to an unprotonated semiquinone anion (Q(A) (-)). The
      accumulation of Q(A) (-) is measured by a rise in fluorescence yield and the
      accumulation of PQH(2) is measured by absorption difference spectrometry. We have
      found that in the absence of a terminal electron acceptor, two chemically diverse
      proton-conducting ionophores (protonophores), 2,6-di-t-butyl-4-(2',2'
      dicyanovinyl)phenol (SF 6847) and carbonylcyanide p
      trifluoromethoxyphenylhydrazone (FCCP), induced oxidation of PQH(2) and quenching
      of chloroplast fluorescence, signifying oxidation of Q(A) (-). The two
      protonophores produced the same effects even when the only recognized pathway of
      PQH(2) oxidation by way of the cytochrome bf complex was inhibited by
      dibromothymoquinone. Two other uncouplers, gramicidin and nigericin, which are
      not protonophores but facilitate proton movement across membranes by other
      mechanisms, were ineffective. These findings are consistent with the operation in
      the oxygen-generating photosystem (photosystem II) of a cyclic, proton-conducting
      pathway.

PMID- 16593901
TI  - Learning algorithms and probability distributions in feed-forward and feed-back
      networks.
AB  - Learning algorithms have been used both on feed-forward deterministic networks
      and on feed-back statistical networks to capture input-output relations and do
      pattern classification. These learning algorithms are examined for a class of
      problems characterized by noisy or statistical data, in which the networks learn
      the relation between input data and probability distributions of answers. In
      simple but nontrivial networks the two learning rules are closely related. Under
      some circumstances the learning problem for the statistical networks can be
      solved without Monte Carlo procedures. The usual arbitrary learning goals of feed
      forward networks can be given useful probabilistic meaning.

PMID- 16593902
TI  - Transfer of resistance traits from carrot into tobacco by asymmetric somatic
      hybridization: Regeneration of fertile plants.
AB  - Transfer of methotrexate and 5-methyltryptophan resistance from carrot (Daucus
      carota) to tobacco (Nicotiana tabacum) was achieved by fusion between leaf
      mesophyll protoplasts of tobacco and irradiated cell culture protoplasts of
      carrot. Some of the regenerated somatic hybrids exhibited normal tobacco
      morphology with coexpression and independent segregation of the transferred
      resistance markers. Chromosomal instability resulted in aneuploid somatic hybrids
      with significantly lower chromosome number than predicted by simple addition of
      parental chromosome number. The methotrexate resistance phenotype was correlated
      with the expression of carrot-specific dihydrofolate reductase as judged by
      isozyme and immunological characteristics of the enzyme. The genomic construct of
      these somatic hybrids made the transmission of the resistance character into the
      next sexual generation possible.

PMID- 16593903
TI  - Stable and heritable inhibition of the expression of nopaline synthase in tobacco
      expressing antisense RNA.
AB  - Antisense nopaline synthase (nos) (D-nopaline synthase; EC 1.5.1.19) RNA is
      stably expressed from the cauliflower mosaic virus 35S promoter in transformed
      tobacco plants. The expression of a previously introduced wild-type nos gene is
      inhibited by the antisense RNA, with less nos enzyme activity detected (by a
      factor of 8-50) depending on the tissue analyzed. The steady-state levels of nos
      mRNA are reduced in the presence of the antisense RNA, implying that mRNA
      degradation is probably the main mode of action for the decrease in expression in
      this system. The antisense RNA-expressing gene and its inhibition of nos
      expression are shown to be heritable, demonstrating that it is a potentially
      useful method for the modification of phenotype.

PMID- 16593904
TI  - Two enzymes involved in biosynthesis of the host-selective phytotoxin HC-toxin.
AB  - Cochliobolus carbonum race 1 produces a cyclic tetrapeptide HC-toxin, which is
      necessary for its exceptional virulence on certain varieties of maize. Previous
      genetic analysis of HC-toxin production by the fungus has indicated that a single
      genetic locus controls HC-toxin production. Enzymes involved in the biosynthesis
      of HC-toxin have been sought by following the precedents established for the
      biosynthetic enzymes of cyclic peptide antibiotics. Two enzymatic activities from
      C. carbonum race 1 were found, a D-alanine- and an L-proline-dependent ATP/PP(i)
      exchange, which by biochemical and genetic criteria were shown to be involved in
      the biosynthesis of HC-toxin. These two activities were present in all tested
      race 1 isolates of C. carbonum, which produce HC-toxin, and in none of the tested
      race 2 and race 3 isolates, which do not produce the toxin. In a genetic cross
      between two isolates of C. carbonum differing at the tox locus, all tox(+)
      progeny had both activities, and all tox(-) progeny lacked both activities.

PMID- 16593905
TI  - Relocating a gene for herbicide tolerance: A chloroplast gene is converted into a
      nuclear gene.
AB  - The chloroplast gene psbA codes for the photosynthetic quinone-binding membrane
      protein Q(B), which is the target of the herbicide atrazine. This gene has been
      converted into a nuclear gene. The psbA gene from an atrazine-resistant biotype
      of Amaranthus hybridus has been modified by fusing its coding region to
      transcription-regulation and transit-peptide-encoding sequences of a bona fide
      nuclear gene. The constructs were introduced into the nuclear genome of tobacco
      by using the Agrobacterium tumor-inducing (Ti) plasmid system, and the protein
      product of nuclear psbA has been identified in the photosynthetic membranes of
      chloroplasts. Recovery of atrazine-tolerant transgenic plants shows that the
      product of the transplanted gene functions in photosynthesis. These experiments
      show that it is possible to modify chloroplast-gene-specified functions via
      nuclear-genome transformation and also raise evolutionary questions.

PMID- 16593906
TI  - Cellular localization of soybean storage protein mRNA in transformed tobacco
      seeds.
AB  - We transformed tobacco plants with a soybean beta-conglycinin gene that encodes
      the 1.7-kilobase beta-subunit mRNA. We showed that the beta-conglycinin mRNA
      accumulates and decays during tobacco seed development and that beta-conglycinin
      mRNA is undetectable in the tobacco leaf. We utilized in situ hybridization to
      localize beta-conglycinin mRNA within the tobacco seed. beta-Conglycinin mRNA is
      not detectable within the endosperm but is localized within specific embryonic
      cell types. The highest concentration of beta-conglycinin mRNA is found in
      cotyledon storage parenchyma cells. We conclude that sequences required for
      embryo expression, temporal control, and cell specificity are linked to the beta
      conglycinin gene, and that factors regulating beta-conglycinin gene expression
      are compartmentalized within analogous soybean and tobacco seed regions.

PMID- 16593907
TI  - Mass mortality of a Caribbean sea urchin: Immediate effects on community
      metabolism and other herbivores.
AB  - The echinoid Diadema antillarum Philippi was an important herbivore in many areas
      of the Caribbean prior to the mass mortality that eliminated 95-99% of the
      individuals throughout the Caribbean in 1983-84. Five days after the mass
      mortality in St. Croix, U.S. Virgin Islands, algal biomass increased by 20% and
      algal community primary productivity dropped on both a per unit area basis (37%
      decrease) and per unit algal biomass basis (61% decrease). This accompanied a 50%
      decrease in the amount of algal biomass removed by herbivores. Concurrent with
      the changes in the algal community were increases in the rates of grazing by
      herbivorous fishes, suggesting that exploitative competition for food was
      occurring between D. antillarum and some herbivorous fish species. These results
      suggest that D. antillarum has an important role in structuring both the producer
      and consumer components of Caribbean coral reef ecosystems.

PMID- 16593908
TI  - Differential expression of genes in potato tubers after wounding.
AB  - Tubers of a common tetraploid species of Solanum tuberosum (Granola) were
      mechanically wounded by slicing. After 18 hr only small differences were
      detectable in the pattern of the steady-state protein extracted from wounded
      versus unwounded tubers. In contrast the protein pattern obtained by in vitro
      translation of mRNA isolated from wounded and unwounded tubers differed
      significantly. A cDNA library was established and screened for wound-induced cDNA
      clones by differential hybridization. Two clones, wun-1 and wun-2, were found
      that corresponded to genes that were highly expressed in wounded potato tubers
      but were not expressed in unwounded tubers. The expression of the gene
      corresponding to wun-1 is detectable 30 min after wounding; the expression of the
      gene corresponding to wun-2 is detectable 4 hr after wounding. The expression of
      both genes (hereafter referred to as wun-1 and wun-2) remains constant for up to
      24 hr after wounding. Interestingly the RNA corresponding to patatin, a major
      storage protein of potato tubers, behaves in the opposite way; it decreases
      dramatically in tubers within 30 min after wounding. The low level of patatin
      mRNA observed in unwounded roots and stems also disappears after wounding. Run
      off transcription experiments, performed with isolated nuclei, indicate that the
      activation of the wound-induced genes as well as the inhibition of the patatin
      gene are controlled at the transcriptional level.

PMID- 16593909
TI  - Quasi-random graphs.
AB  - We introduce a large equivalence class of graph properties, all of which are
      shared by so-called random graphs. Unlike random graphs, however, it is often
      relatively easy to verify that a particular family of graphs possesses some
      property in this class.

PMID- 16593910
TI  - Role of algal eukaryotes in subtidal columnar stromatolite formation.
AB  - Columnar stromatolites were abundant and widespread in the Proterozoic but are
      exceedingly rare in modern seas. Consequently, the stromatolites at Hamelin Pool
      in Shark Bay, Western Australia, have been widely interpreted as unique modern
      analogs of ancient stromatolites constructed by complex communities of
      cyanobacteria. However, the Shark Bay columnar stromatolites contain sediment
      that is unusually coarse for stromatolites both ancient and modern, and the
      subtidal columnar stromatolites have a significant component of algal eukaryotes
      dominated by motile diatoms with mucilaginous tubes. This suggests that Shark Bay
      columnar stromatolites are not strict analogs for most ancient cyanobacterial
      stromatolites, least of all for those from subtidal environments. We argue that
      algal eukaryotes may play a substantial role in the formation and maintenance of
      subtidal columnar stromatolites at Shark Bay and are capable of trapping coarse
      sediment. In contrast, cyanobacteria have difficulty in trapping coarse sediment
      and produce essentially fine-grained stromatolites. We propose that there are two
      major types or end members of Recent marine stromatolites: (i) eualgal
      cyanobacterial stromatolites that are generally coarse-grained, and (ii)
      cyanobacterial stromatolites that are generally fine-grained.

PMID- 16593911
TI  - Gordan-Capelli series in superalgebras.
AB  - We derive two Gordan-Capelli series for the supersymmetric algebra of the tensor
      product of two [unk](2)-graded [unk]-vector spaces U and V, being [unk] a field
      of characteristic zero. These expansions yield complete decompositions of the
      supersymmetric algebra regarded as a pl(U)- and a pl(V)- module, where pl(U) and
      pl(V) are the general linear Lie superalgebras of U and V, respectively.

PMID- 16593912
TI  - Size of bacterial ice-nucleation sites measured in situ by radiation inactivation
      analysis.
AB  - Four bacterial species are known to catalyze ice formation at temperatures just
      below 0 degrees C. To better understand the relationship between the molecular
      structure of bacterial ice-nucleation site(s) and the quantitative and
      qualitative features of the ice-nucleation-active phenotype, we determined by
      gamma-radiation analysis the in situ size of ice-nucleation sites in strains of
      Pseudomonas syringae and Erwinia herbicola and in Escherichia coli HB101 carrying
      the plasmid pICE1.1 (containing a 4-kilobase DNA insert from P. syringae that
      confers ice-nucleation activity). Lyophilized cells of each bacterial strain were
      irradiated with a flux of gamma radiation from 0 to 10.2 Mrad (1 Mrad = 10(6)
      J/kg). Differential concentrations of active ice nuclei decreased as a first
      order function of radiation dose in all strains as temperature was decreased from
      -2 degrees C to -14 degrees C in 1 degrees C intervals. Sizes of ice nuclei were
      calculated from the gamma-radiation flux at which 37% of initial ice nuclei
      active within each 1 degrees C temperature interval remained. The minimum mass of
      a functional ice nucleus, active only between -12 degrees C and -13 degrees C,
      was about 150 kDa for all strains. The size of ice nuclei increased
      logarithmically with increasing temperature from -12 degrees C to -2 degrees C,
      where the estimated nucleant mass was 19,000 kDa. The ice nucleant in these three
      bacterial species may represent an oligomeric structure, composed at least in
      part of an ice gene product that can self-associate to assume many possible
      sizes.

PMID- 16593913
TI  - Electron spin resonance of charge carriers in chlorophyll a/water micelles.
AB  - Chlorophyll a/water micelles (P740) prepared in hydrocarbon media have been shown
      by small-angle neutron scattering to consist of hollow cylinders whose surface is
      formed of a monolayer of chlorophyll crosslinked by water. The micelles can be
      reversibly oxidized or reduced to generate highly mobile holes or electrons that
      undergo rapid, one-dimensional transport along the chains of chlorophyll
      macrocycles comprising the surface of the micelles. Large pi-pi overlap within
      the chains facilitates the one-dimensional charge transport and is expected to do
      the same for energy transport. Structural defects in the micelle surface act as
      boundaries for charge transport, confining the spins to one-dimensional domains
      of approximately 200 macrocycles. The one-dimensional transport within the
      limited domains results in motionally narrowed electron spin resonance lines with
      some residual inhomogeneous broadening. Although the chlorophyll a incorporated
      in micelles is more easily oxidized than is monomeric chlorophyll a, it is much
      more resistant to chemical alteration.

PMID- 16593914
TI  - Phylogeographic population structure of Red-winged Blackbirds assessed by
      mitochondrial DNA.
AB  - A continent-wide survey of restriction-site variation in mitochondrial DNA
      (mtDNA) of the Red-winged Blackbird (Agelaius phoeniceus) was conducted to assess
      the magnitude of phylogeographic population structure in an avian species. A
      total of 34 mtDNA genotypes was observed among the 127 specimens assayed by 18
      restriction endonucleases. Nonetheless, population differentiation was minor, as
      indicated by (i) small genetic distances in terms of base substitutions per
      nucleotide site between mtDNA genotypes (maximum P approximately 0.008) and by
      (ii) the widespread geographic distributions of particular mtDNA clones and
      phylogenetic arrays of clones. Extensive morphological differentiation among
      redwing populations apparently has occurred in the context of relatively little
      phylogenetic separation. A comparison between mtDNA data sets for Red-winged
      Blackbirds and deermice (Peromyscus maniculatus) also sampled from across North
      America shows that intraspecific population structures of these two species
      differ dramatically. The lower phylogeographic differentiation in redwings is
      probably due to historically higher levels of gene flow.

PMID- 16593915
TI  - Sigma-phase packing of icosahedral clusters in 780-atom tetragonal crystals of
      Cr(5)Ni(3)Si(2) and V(15)Ni(10)Si that by twinning achieve 8-fold rotational
      point-group symmetry.
AB  - A 780-atom primitive tetragonal unit with edges 27.3, 27.3, and 12.6 A is
      assigned to rapidly solidified Cu(5)Ni(3)Si(2) and V(15)Ni(10)Si by analysis of
      electron diffraction photographs with the assumption that the crystals contain
      icosahedral clusters. There are thirty 26-atom clusters at the sigma-phase
      positions. Apparent 8-fold symmetry results from 45 degrees twinning on the basal
      plane.

PMID- 16593916
TI  - Existence for large times of finite amplitude elastic waves arising from small
      disturbances.
AB  - This paper deals with strict solutions u(i)(t, x(1), x(2), x(3)) of a system of
      quasi-linear equations [Formula: see text] with u' = ([unk](x(i) )u(k)), and i,
      k, r, s ranging over 1, 2, 3. For given initial conditions u(i) =
      epsilonf(i)(x(1), x(2), x(3)), [unk](t)u(i) = epsilong(x(1), x(2), x(3)) for t =
      0 the life-span T(epsilon) is the supremum of all t > 0 to which the u(i) can be
      extended as strict solutions for all x. It is shown that lim inf(epsilon-->0)
      epsilon log T(epsilon) > 0 for C(ikrs), f(i), g(i) [unk] C(0) (infinity), and
      C(ikrs) = C(rsik), C(ikrs)(0) = 0.

PMID- 16593917
TI  - Locally asymptotically rank-based procedures for testing autoregressive moving
      average dependence.
AB  - The problem of testing a given autoregressive moving average (ARMA) model (in
      which the density of the generating white noise is unspecified) against other
      ARMA models is considered. A distribution-free asymptotically most powerful test,
      based on a generalized linear serial rank statistic, is provided against
      contiguous ARMA alternatives with specified coefficients. In the case in which
      the ARMA model in the alternative has unspecified coefficients, the asymptotic
      sufficiency (in the sense of Hajek) of a finite-dimensional vector of rank
      statistics is established. This asymptotic sufficiency is used to derive an
      asymptotically maximin most powerful test, based on a generalized quadratic
      serial rank statistic. The asymptotically maximin optimal test statistic can be
      interpreted as a rank-based, weighted version of the classical Box-Pierce
      portmanteau statistic, to which it reduces, in some particular problems, under
      gaussian assumptions.

PMID- 16593918
TI  - High-sensitivity neutron diffraction of membranes: Location of the Schiff base
      end of the chromophore of bacteriorhodopsin.
AB  - THREE IMPORTANT EVENTS IN THE FUNCTIONAL CYCLE OF BACTERIORHODOPSIN OCCUR AT THE
      CHROMOPHORE: the primary absorption of light, the isomerization from the alltrans
      to the 13-cis form, and the deprotonation and reprotonation of its Schiff base.
      The protonated Schiff base linkage of the chromophore with lysine-216 plays an
      essential role in the color regulation of the pigment and is most likely directly
      involved in the charge translocation of this light-driven proton pump. Although
      much is known about the structure of the protein, the position of this key
      functional group has not yet been determined. We have synthesized a retinal in
      which the five protons closest to the Schiff base are replaced by deuterons. The
      labeled retinal was spontaneously incorporated into bacteriorhodopsin by using a
      mutant of Halobacterium halobium that is deficient in the synthesis of retinal.
      The position of the labeled Schiff base end of the chromophore was determined in
      the two-dimensional projected density of dark-adapted bacteriorhodopsin by
      neutron diffraction. The result fits very well with our previous work using
      retinals that were selectively deuterated in the middle of the polyene chain or
      in the cyclohexene ring. A coherent structure emerges with the three labeled
      positions on one line, separated by distances that are in good agreement with the
      tilt angle of the polyene chain (about 20 degrees ). The chromophore is located
      in the interior of the protein with the nitrogen of the Schiff base between
      helices 2 and 6 and with its ring in the vicinity of helix 4. Our results show
      that it is possible to locate a small group containing as few as five deuterons
      in a membrane protein of molecular weight 27,000.

PMID- 16593919
TI  - On the advantage of being different: Nest predation and the coexistence of bird
      species.
AB  - A long-standing debate in ecology centers on identifying the processes that
      determine which species coexist in a local community. Partitioning of resources,
      where species differ in resource use, is often thought to reflect the primary
      role of competition in determining coexistence of species. However, in theory
      predation can favor similar patterns. This theory premises that predators
      increase their search intensity with increasing density of prey. One set of
      experiments reported here supports this premise based on predators that search
      for bird nests. A second set of experiments documents that predation rates are
      lower when nest sites are partitioned among different sites than when the same
      number of nests are placed in similar sites. Moreover, predation rates on
      experimental nests are more similar to rates on real nests when experimental
      nests are partitioned among different sites. These results provide support for a
      hypothesis that nest predation is a process that can favor coexistence of bird
      species that partition resources, where nest sites are the resources.

PMID- 16593920
TI  - The spectrum of NGC 7027 (367-650 nm).
AB  - NGC 7027 shows the richest spectrum of any known gaseous nebula. In the region of
      the spectrum surveyed we have measured lines of ions of H, He, C, N, O, F, Ne,
      Mg, Si, P, S, Cl, Ar, K, Ca, Mn, and Fe using the new Hamilton Echelle
      Spectrograph of Lick Observatory with a charge-coupled device (CCD) detector.
      Since a CCD is a linear detector, whereas photographic emulsions used in the most
      comprehensive previous studies were not, a considerable enhancement in the
      accuracy of line intensity measurements is possible.

PMID- 16593921
TI  - Structure of the orthorhombic form of Mn(2)Al(7), Fe(2)Al(7), and
      (Mn(0.7)Fe(0.3))(2)Al(7) that by twinning produces grains with decagonal point
      group symmetry.
AB  - Analysis of electron diffraction photographs of grains of Mn(2)Al(7), Fe(2)Al(7),
      and (Mn(0.7)Fe(0.3))(2)Al(7) leads to the conclusion that they are 5-fold twins
      of a 1664-atom orthorhombic crystal with a = 32.86 A, b = 31.23 A, and c = 24.80
      A and with 16 icosahedral clusters of 104 atoms in positions shifted by small
      amounts from those of the cubic beta-tungsten structure.

PMID- 16593922
TI  - Water-stress-induced changes in the abscisic acid content of guard cells and
      other cells of Vicia faba L. leaves as determined by enzyme-amplified
      immunoassay.
AB  - A highly sensitive, solid-phase, enzyme-amplified immunoassay for the plant
      growth regulator (+)-abscisic acid (ABA) was developed. The assay sensitivity
      (0.2-10 fmol) was sufficient for analyzing free ABA in homogeneous tissue samples
      dissected from Vicia faba L. leaves. Eight hours after detached leaves had been
      desiccated to 10% loss of fresh weight, the bulk leaf ABA content increased from
      </=0.2 to 6.2 ng.(mg dry weight)(-1). Epidermal tissue, spongy parenchyma cells,
      and palisade parenchyma cells from this water-stressed leaf had the following ABA
      contents, respectively: 4.8, 9.4, and 9.0 ng.(mg dry weight)(-1). Guard cells,
      which respond to exogenous ABA by losing solutes and volume, were also assayed.
      When they were dissected from control (fully hydrated) leaves, their ABA content
      was approximately 0.7 fg.(cell pair)(-1) [[unk]0.2 ng.(mg dry weight)(-1)]. In
      contrast, the ABA content of guard cells of water-stressed leaves was
      approximately 17.7 fg.(cell pair)(-1). These results indicate that ABA
      accumulation in a highly stressed V. faba leaflet is generalized; guard cells
      contain only 0.15% of bulk leaf ABA. The time course for loss of ABA from guard
      cells of a floating epidermal peel was studied. There was little loss within 30
      min, but after 4 hr, the ABA content was only 17% of the original value. These
      results indicate that the bulk of guard cell ABA is not readily diffusible (i.e.,
      probably not apoplastic). The results also indicate that common laboratory
      procedures results in lowered guard cell ABA content.

PMID- 16593923
TI  - Chloroplast DNA evolution and systematics of Phanerophlebia (Dryopteridaceae) and
      related fern genera.
AB  - Restriction site variation in chloroplast DNA was examined in the neotropical
      fern genus Phanerophlebia and in selected species of the related Asiatic genus
      Cyrtomium and the cosmopolitan progenitor of these two, Polystichum. A total of
      103 restriction site mutations was identified; these were used to construct
      phylogenetic networks and trees based on Wagner and Dollo parsimony and Fitch
      Margoliash distance algorithms. The analyses provided evidence that
      Phanerophlebia did not arise from Cyrtomium. Both genera are convergent
      descendants from different progenitor groups in Polystichum, and Asiatic
      Cyrtomium is more closely related to temperate New World Polystichum than it is
      to neotropical Phanerophlebia. Reticulate venation, previously considered an
      important taxonomic character for infrageneric classification in Phanerophlebia,
      most likely evolved independently twice within the genus. Diploid maternal
      progenitors are suggested for two of four tetraploid species analyzed, and
      species-level distinctions for two closely related taxa of Phanerophlebia are
      questioned.

PMID- 16593924
TI  - Exclusion of male mitochondria and plastids during syngamy in barley as a basis
      for maternal inheritance.
AB  - It is known from genetic analyses that maternal inheritance of cytoplasmic
      organelles is the rule among plants and animals. Although recognized as one of
      several possible mechanisms for strictly maternal cytoplasmic inheritance,
      exclusion of sperm cytoplasm at the time of gametic fusion has remained poorly
      documented for the flowering plants. In the present investigation, enucleated,
      cytoplasmic bodies approximately the size of intact, prefusion sperm cells have
      been observed within degenerated synergids and adjacent to recently fertilized
      egg cells. A complete series of ultrathin sections (68 sections) through such a
      cytoplasmic body revealed 59 mitochondria, 3 plastids, 7 dictyosomes, and a large
      vacuole with no limiting membrane. This structure is interpreted as the entire
      male cytoplasm that was left outside the egg during fusion between egg and sperm.
      The observation of only one cytoplasmic body per embryo sac may indicate a
      preliminary fusion between sperm cells or, more likely, the existence of a
      fundamentally different mechanism of fertilization between the second sperm and
      the central cell.

PMID- 16593925
TI  - Cell expansion and single-cell separation induced by colchicine in suspension
      cultured soybean cells.
AB  - Single plant cells have been obtained without the preparation of protoplasts by
      culturing pieces of soybean callus tissue with colchicine. Cell expansion and
      separation were evoked by colchicine (1 mM) within a week of culture. Microscopic
      observation showed that cells took on a spherical shape in the presence of
      colchicine and then separated into single cells. Addition of colchicine to the
      culture medium did not affect the composition of cell wall polysaccharides, but a
      uronic acid-rich extracellular polysaccharide appeared during cell expansion and
      separation. Addition of microtubule stabilizers, glycerol (300 mM) or dimethyl
      sulfoxide [3% (vol/vol)], inhibited the secretion of the polysaccharide as well
      as cell expansion and separation. The extracellular polysaccharide elicited by
      colchicine was isolated by ion-exchange chromatography on DEAE-Sepharose and gel
      filtration on Sepharose CL-6B from the conditioned medium of colchicine-treated
      soybean cells. The purified 18-kDa polysaccharide immediately enhanced cell
      expansion and separation when added to soybean callus tissue cultured in medium
      containing colchicine, even at low concentrations (0.1 mM). The polysaccharide
      was composed of galacturonic acid and, after digestion with a pectinase
      preparation, had no effect on the cells. Methylation analysis suggests that the
      polysaccharide consists of approximately 100 sequential alpha-1,4-galacturonic
      acids. The galacturonan increased the viability of separated cells cultured in
      medium containing colchicine, and the single cells obtained did not produce a
      wound-response callose. (Aminoethoxyvinyl)glycine, a specific inhibitor of
      ethylene production, extensively decreased the cell expansion and separation but
      did not inhibit the formation of the extracellular polysaccharide, suggesting
      that the polysaccharide may exert its effect by stimulating ethylene production.

PMID- 16593926
TI  - Mitochondrial DNA rearrangement associated with fertility restoration and
      cytoplasmic reversion to fertility in cytoplasmic male sterile Phaseolus vulgaris
      L.
AB  - Restoration of pollen fertility to cytoplasmic male sterile (CMS) Phaseolus
      vulgaris by a nuclear restorer gene provides a system for studying nuclear
      cytoplasmic interactions. Introduction of a nuclear restorer gene to this CMS
      line of P. vulgaris (CMS-Sprite) results in a mitochondrial genome rearrangement
      similar to that observed upon spontaneous cytoplasmic reversion to fertility.
      Three spontaneous heritable cytoplasmic revertants were derived from CMS-Sprite.
      Five fully fertile restored lines were also produced by using restorer line R-351
      (BC(3)F(3) populations). Comparison of the mitochondrial DNA restriction patterns
      of CMS-Sprite, the three fertile revertants, and the five restored lines revealed
      loss of a 6.0-kilobase (kb) Pst I fragment in all restored and revertant lines.
      Southern hybridizations with a 1.3-kb BamHI clone, internal to the 6.0-kb Pst I
      fragment, as a probe revealed two configurations of 6.0-kb homologous sequences
      in the sterile cytoplasm; one of the configurations was lost upon reversion or
      restoration. Mitochondrial DNA rearrangement has thus been observed upon
      restoration by a nuclear restorer gene in this CMS system.

PMID- 16593927
TI  - Douglas' solution of the Plateau problem.
AB  - Using ideas suggested by some recent developments in string theory, we give here
      an elementary demonstration of one of the key steps in Douglas' celebrated proof
      of the existence of solutions of the Plateau problem in n dimensions.

PMID- 16593928
TI  - Hairy roots are more sensitive to auxin than normal roots.
AB  - Responses to auxin of Lotus corniculatus root tips or protoplasts transformed by
      Agrobacterium rhizogenes strains 15834 and 8196 were compared to those of their
      normal counterparts. Three different types of experiments were performed,
      involving long-term, medium-term, or short-term responses to a synthetic auxin, 1
      naphthaleneacetic acid. Root tip elongation, proton excretion by root tips, and
      transmembrane electrical potential difference of root protoplasts were measured
      as a function of exogenous auxin concentration. The sensitivity of hairy root
      tips or protoplasts to exogenous auxin was found to be 100-1000 times higher than
      that of untransformed material.

PMID- 16593929
TI  - Icosahedral quasicrystals as twins of cubic crystals containing large icosahedral
      clusters of atoms: The 1012-atom primitive cubic structure of Al(6)CuLi(3), the C
      phase Al(37)Cu(3)Li(21)Mg(3), and GaMg(2)Zn(3).
AB  - Single-grain precession x-ray diffraction photographs of Al(6)CuLi(3) have been
      successfully indexed on the basis of icosahedral twinning of cubic crystals with
      a 1012-atom primitive cubic unit with edge 25.70 A, giving support to the
      proposal that the so-called icosahedral quasicrystals are twins of crystals
      containing eight large icosahedral clusters in the beta-W arrangement. In this
      compound two of the clusters consist of 104 atoms and six consist of 136 atoms,
      with 24 atoms shared. The same structure is assigned to the C-phase,
      Al(37)Cu(3)Li(21)Mg(3), and to GaMg(2)Zn(3). A theory of icosahedral
      quasicrystals and amorphous metals is described.

PMID- 16593930
TI  - Factor inducing Agrobacterium tumefaciens vir gene expression is present in
      monocotyledonous plants.
AB  - Agrobacterium tumefaciens harboring the tumor-inducing Ti plasmid incites crown
      gall tumor on dicotyledonous species. Upon infection of these plants, Ti plasmid
      DNA sequence is stably transferred (T-DNA) by unknown mechanisms to plant cells
      to be integrated into nuclear DNA. The T-DNA processing and transfer require the
      expression of vir (virulence) genes on the Ti plasmid, which are known to be
      induced by certain phenolic compounds released from cells at the wounded
      inoculation site. The results of the present study demonstrate that wheat and
      oats contain a substance(s) that induces vir gene expression, yet the inducing
      substance of wheat differs from the phenolic inducers in that it is hydrophilic
      and has a molecular weight of several thousand. The novel inducer was not
      detectable in the exudates of seedlings of these plants but was found in an
      extract from the transition region between shoot and root of the seedlings and
      also in extracts from the seeds, bran, and germ. This finding suggests that T-DNA
      processing and possibly its transfer should take place when Agrobacterium invades
      suitable tissues of monocotyledonous plants.

PMID- 16593931
TI  - Determination of the aggregate size in detergent solution of the light-harvesting
      chlorophyll a/b-protein complex from chloroplast membranes.
AB  - The molecular mass of an oligomeric integral membrane protein, the light
      harvesting chlorophyll a/b-protein complex from the photosynthetic membranes of
      chloroplasts, has been determined in detergent solution by analytical
      ultracentrifugation and measurement of the density increment at constant chemical
      potential of all diffusible solutes. The technique used eliminates any problems
      resulting from detergent binding to the protein, is independent of the particular
      detergent used (in this case the nonionic n-octyl beta-D-glucopyranoside), and
      gives the apparent weight-average molecular mass at different protein
      concentrations, allowing extrapolation to zero concentration. It means that the
      solutions of the complex must be brought to dialysis equilibrium with the solvent
      detergent solution and also requires a reliable method for measuring the protein
      concentration, for which amino acid analysis was used. The detergent-solubilized
      complex was a trimer that dissociated into monomers and dimers at low protein
      concentration. The accurate concentration determinations also allowed the molar
      chlorophyll-to-protein ratio to be measured as 15, corresponding to 8 chlorophyll
      a and 7 chlorophyll b molecules.

PMID- 16593932
TI  - On the evolution of the adaptation of Lophopyrum elongatum to growth in saline
      environments.
AB  - Most species of the genus Lophopyrum Love (Agropyron Geartn.) grow in saline
      environments and are more tolerant of saline stress than the species of the
      related genus Triticum L. A 56-chromosome amphiploid from the cross Triticum
      aestivum cv. Chinese Spring x Lophopyrum elongatum exceeded Chinese Spring in
      salt tolerance, measured as plant dry-matter production and seed yield in
      solution cultures with 250 mM NaCl. Thus, the adaptation of Lophopyrum to saline
      environments is expressed in the wheat genetic background. None of the disomic
      additions or substitutions of L. elongatum chromosomes in Chinese Spring showed a
      similar level of saline stress tolerance, which indicates that the trait depends
      on the activity of genes on more than one chromosome. Comparisons of disomic
      additions, double monosomic additions from half-diallel crosses among disomic
      additions, and disomic substitutions of L. elongatum chromosomes in Chinese
      Spring with Chinese Spring indicated that the enhanced salt tolerance of the
      amphiploid is primarily controlled by genes with minor effects on three of the
      seven chromosomes, 3E, 4E, and 7E, interacting in a largely additive manner. The
      salt tolerance of L. elongatum additionally depends on several minor nonadditive
      gene interactions. It is concluded that the adaptation of L. elongatum to growth
      in saline environments evolved by accumulation of new alleles in a number of
      loci, each with a relatively small effect on salt tolerance. It is further
      inferred that most of these new alleles were codominant to the original alleles
      and were able to act independently in enhancing salt tolerance.

PMID- 16593933
TI  - Isolation of genes involved in nodulation competitiveness from Rhizobium
      leguminosarum bv. trifolii T24.
AB  - Rhizobium leguminosarum bv. trifolii T24 produces a potent anti-rhizobial
      compound, trifolitoxin, and exclusively nodulates clover roots when in mixed
      inoculum with trifolitoxin-sensitive strains of R. leguminosarum bv. trifolii
      [Schwinghamer, E. A. & Belkengren R. P. (1968) Arch. Mikrobiol. 64, 130-145]. In
      the present study, the isolation of trifolitoxin production and resistance genes
      is described. A cosmid genomic library of T24 was prepared in pLAFR3. No
      trifolitoxin expression was observed in the resulting Escherichia coli cosmid
      clones. One cosmid clone was identified that restored trifolitoxin production and
      nodulation competitiveness in three nonproducing mutants of T24. The recombinant
      plasmid from this cosmid clone, pTFX1, also conferred trifolitoxin production and
      resistance when transferred to symbiotically effective strains of R.
      leguminosarum bvs. trifolii, phaseoli, and viceae. Cosmid pTFX1 also conferred
      expression of trifolitoxin production when present in strains of Rhizobium
      meliloti and Agrobacterium tumefaciens. No trifolitoxin expression was observed
      in strains of Bradyrhizobium japonicum or Rhizobium sp. (cowpea) with pTFX1.
      Southern blot analysis with a biotinylated pTFX1 probe did not suggest that these
      genes were plasmid-borne. Transfer of pTFX1 to T24 or its derivatives resulted in
      6- to 10-fold higher level of trifolitoxin production than wild-type T24.

PMID- 16593934
TI  - Mechanisms for light-dependent regulation of ribulose-1,5-bisphosphate
      carboxylase activity and photosynthesis in intact leaves.
AB  - The mechanisms involved in the in vivo light-dependent regulation of ribulose-1,5
      bisphosphate (RbuP(2)) carboxylase [3-phospho-D-glycerate carboxy-lyase
      (dimerizing), EC 4.1.1.39] activity in intact leaves were studied. In the three
      species examined, Phaseolus vulgaris, Beta vulgaris, and Spinacea oleracea, the
      regulated level of RbuP(2) carboxylase activity (assayed in vitro with saturating
      substrate) was highly correlated (r = 0.96) with the rate of net CO(2) uptake of
      the corresponding leaves measured over a wide range of photosynthetic photon flux
      density (PPFD). However, the mechanisms by which the enzyme was regulated
      differed between these species. In Phaseolus, the inhibitor 2-carboxyarabinitol 1
      phosphate (CAP) accounted for all of the PPFD-dependent regulation of RbuP(2)
      carboxylase activity. A similar compound was detected in Beta, and changes in its
      concentration accounted for about half of the PPFD-dependent regulation of enzyme
      activity in this species. No CAP was detected in Spinacea, but evidence we
      obtained suggests that a different inhibitor (possibly RbuP(2)) accounts for a
      significant portion of the PPFD-dependent regulation of enzyme activity in this
      species. Changes in the activation state of the enzyme were observed with Beta
      and Spinacea, while in Phaseolus the enzyme was apparently fully activated at all
      PPFD levels. These results indicate that plant species may differ markedly in the
      mechanisms they use to regulate RbuP(2) carboxylase activity as PPFD changes. The
      results also suggest that tight binding inhibitors are a more widespread
      mechanism for regulation of this enzyme than previously thought. Furthermore, the
      results establish the importance of such inhibitors in regulating both the
      activity of RbuP(2) carboxylase and whole leaf photosynthesis over a range of
      PPFD.

PMID- 16593935
TI  - The possible role of ammonia in phototaxis of migrating slugs of Dictyostelium
      discoideum.
AB  - Previously we showed that the rising cell masses of cellular slime molds orient
      away from high concentrations of ammonia gas, presumably by speeding up the cells
      on one side. Here we show that in the same way NH(3) could also be involved in
      the highly sensitive phototaxis found in the migrating slugs of Dictyostelium
      discoideum. We have evidence that light increases their speed of migration and
      their production of NH(3). Since unilateral light is concentrated on the distal
      side of a cell mass by the "lens effect," this leads to the obvious hypothesis
      that the light stimulates the local production of NH(3), which, in turn,
      stimulates the cells in the illuminated region to move faster.

PMID- 16593936
TI  - Aluminum toxicity and forest decline.
AB  - The rate of root elongation in seedlings of Picea abies was drastically inhibited
      by exposure to AlCl(3) at 800 or 1200 mumol/dm(3) in nutrient solutions. A 35-day
      exposure to Al at 700 mumol/dm(3) reduced Mg and Ca in roots and needles of the
      seedlings. The Mg content of needles was reduced to levels considered to be
      critical for Mg deficiency. In investigations of (45)Ca uptake into roots,
      exposure to Al at 100-800 mumol/dm(3) reduced (45)Ca uptake by 77-92%,
      respectively. By using x-ray microanalysis, the distribution of Al, Mg, Ca, and K
      was found to be similar in roots of Picea abies seedlings grown in solution
      culture and in roots collected from declining spruce stands at Solling, F.R.G. In
      solution culture Al displaced Mg and Ca in the root cortex. A mechanism of Al
      toxicity for root growth and ion uptake is proposed, and its relevance to forest
      decline is discussed.

PMID- 16593937
TI  - Variable expression of extracellular polysaccharide in the marine bacterium
      Pseudomonas atlantica is controlled by genome rearrangement.
AB  - Production of extracellular polysaccharide by the marine bacterium Pseudomonas
      atlantica is a variable trait. Strains that produce extracellular polysaccharide
      (EPS(+)) have a mucoid colony phenotype, but during cultivation in the laboratory
      nonmucoid, EPS(-) variants arise that have a crenated colony morphology. This
      change is reversible since crenated variants rapidly switch to the original
      mucoid phenotype. We have cloned the locus (eps) controlling variable expression
      of EPS production by screening a recombinant cosmid library for clones that
      restore EPS production in the crenated variant. By using eps as a probe of
      genomic structure in variant strains, expression of EPS production was found to
      be controlled by a specific DNA rearrangement. Insertion of a 1.2-kilobase-pair
      DNA sequence in the eps locus results in EPS(-), whereas excision of the sequence
      restores the EPS(+) phenotype. Properties of the rearrangement suggest the
      involvement of a mobile genetic element. The possible significance of this DNA
      rearrangement to the survival of P. atlantica in the ocean is discussed.

PMID- 16593938
TI  - Expression of modified rye ribosomal RNA genes in wheat.
AB  - Several wheats (Triticum aestivum L. em Thell.) containing the short arm of
      chromosome 1R from rye (Secale cereale L.) translocated to the long arm of wheat
      chromosome 1B were examined, by in situ hybridization with a biotinylated probe,
      for the expression of rye rRNA genes located in the nucleolus-organizing region
      (NOR) present on the short arm of 1R. The wheats analyzed contain a reduced rye
      NOR band, identified by a C-banding technique, that was assumed to have resulted
      from a deletion that reduced the number of rRNA genes and spacer units. Genes
      being actively transcribed could be recognized as dispersed label on DNA within
      the nucleolus, while those genes that were inactive were seen as condensed label.
      After in situ hybridization with a biotinylated rye NOR spacer probe, no evidence
      of rye rRNA gene activity was detected in the plants containing a reduced rye NOR
      band. Biotin-labeling of chromosomes containing a normal-sized rye NOR locus
      showed a degree of rye activity consistent with the results of a previous study
      that used a radioactive probe detected by autoradiography. It was determined
      previously that rye rRNA genes in a wheat background show significantly less
      activity than in diploid rye because the spacer units between the rRNA genes of
      rye are smaller than those of wheat, and in cereals the ribosomal locus with the
      larger spacer unit is preferentially transcribed. The present results indicate
      that the number of spacer units is also important in determining which NOR locus
      (i.e., rye or wheat) will be expressed when several ribosomal loci are present in
      a wheat background.

PMID- 16593939
TI  - Altered regulation of lipid biosynthesis in a mutant of Arabidopsis deficient in
      chloroplast glycerol-3-phosphate acyltransferase activity.
AB  - The leaf membrane lipids of many plant species, including Arabidopsis thaliana
      (L.) Heynh., are synthesized by two complementary pathways that are associated
      with the chloroplast and the endoplasmic reticulum. By screening directly for
      alterations in lipid acyl-group composition, we have identified several mutants
      of Arabidopsis that lack the plastid pathway because of a deficiency in activity
      of the first enzyme in the plastid pathway of glycerolipid synthesis, acyl-ACP:sn
      glycerol-3-phosphate acyltransferase (EC 2.3.1.15) (where ACP is acyl carrier
      protein). The lesion results in an increased synthesis of lipids by the
      cytoplasmic pathway that largely compensates for the loss of the plastid pathway
      and provides nearly normal amounts of all the lipids required for chloroplast
      biogenesis. However, the fatty acid composition of the leaf membrane lipids of
      the mutants is altered because the acyltransferases associated with the two
      pathways normally exhibit different substrate specificities. The remarkable
      flexibility of the system provides an insight into the nature of the regulatory
      mechanisms that allocate lipids for membrane biogenesis.

PMID- 16593940
TI  - mRNAs encoding ribulose-1,5-bisphosphate carboxylase remain bound to polysomes
      but are not translated in amaranth seedlings transferred to darkness.
AB  - When light-grown seedlings of amaranth are transferred to total darkness,
      synthesis of the large subunit (LS) and small subunit (SS) of ribulose-1,5
      bisphosphate carboxylase [RbuP(2)Case; 3-phospho-D-glycerate carboxylase
      (dimerizing), EC 4.1.1.39] is rapidly depressed. This reduction in RbuP(2)Case
      synthesis occurs in the absence of any corresponding changes in levels of
      functional mRNA for either subunit. Four hours after light-to-dark transition
      little, if any, changes in the distribution of LS and SS mRNAs on polysomes could
      be detected. The association of these mRNAs with polysomes was authenticated by
      treatment with RNase A or puromycin. Furthermore, polysomes were able to
      synthesize LS and SS precursor in cell-free translation systems supplemented with
      inhibitors of initiation. Therefore, during a light-to-dark transition LS and SS
      mRNAs remained bound to polysomes but were not translated in vivo, suggesting
      that control is exercised, in part, at the translational elongation step.

PMID- 16593941
TI  - A stable bifunctional antisense transcript inhibiting gene expression in
      transgenic plants.
AB  - Tobacco plants expressing constitutive chloramphenicol acetyltransferase (CAT; EC
      2.3.1.28) activity were obtained by transformation with a chimeric CAT gene
      driven by the cauliflower mosaic virus 19S promoter. Plants expressing different
      levels of CAT activity were retransformed with vectors containing CAT sequences
      transcriptionally fused in the antisense orientation between the coding region of
      the hygromycin-resistance gene and the 3' end of the nopaline synthase gene.
      Several plants regenerated on high concentrations of hygromycin exhibited a loss
      of CAT activity, whereas plants retransformed with a vector conferring hygromycin
      resistance but lacking the antisense CAT sequence showed no reduction in CAT
      activity. RNA blot analysis revealed a strong correlation between the degree of
      CAT gene inactivation and the levels of stable antisense transcripts accumulated.
      The possibility that CAT gene inactivation was due to transferred DNA instability
      was discounted since a kanamycin-resistance gene contiguous with the CAT gene was
      expressed normally, and DNA blot analysis indicated no loss or rearrangements of
      the transferred DNA fragments. Thus, the imposed selection pressure enabled the
      selection of plants expressing high levels of stable bifunctional antisense
      transcripts that inhibited the activity of the targeted gene.

PMID- 16593942
TI  - Transfer of foreign genes into intact maize cells with high-velocity
      microprojectiles.
AB  - This report describes a process for delivering foreign genes into maize cells
      that does not require the removal of cell walls and is capable of delivering DNA
      into embryogenic and nonembryogenic tissues. Plasmid harboring a chimeric
      chloramphenicol acetyltransferase (CAT) gene was adsorbed to the surface of
      microscopic tungsten particles (microprojectiles). These microprojectiles were
      then accelerated to velocities sufficient for penetrating the cell walls and
      membranes of maize cells in suspension culture. High levels of CAT activity were
      consistently observed after bombardment of cell cultures of the cultivar Black
      Mexican Sweet, which were comparable to CAT levels observed after electroporation
      of protoplasts. Measurable increases in CAT levels were also observed in two
      embryogenic cell lines after bombardment. Gene expression was observed only when
      an intron from the alcohol dehydrogenase 1 gene of maize was ligated between the
      35S promoter and the CAT coding region. CAT activity was detected in cell
      cultures bombarded with microprojectiles with an average diameter of 1.2 mum, but
      not after bombardment with microprojectiles 0.6 or 2.4 mum in diameter.
      Bombarding the same sample several times was found to markedly enhance CAT
      activity. These results demonstrate that the particle bombardment process can be
      used to deliver foreign DNA into intact cells of maize. Because this process
      circumvents the difficulties associated with regenerating whole plants from
      protoplasts, the particle bombardment process may provide significant advantages
      over existing DNA delivery methods for the production of transgenic maize plants.
      In addition, the process should be of value for studying transient and stable
      gene expression within intact cells and tissues.

PMID- 16593943
TI  - An enhancer-like element present in the promoter of a T-DNA gene from the Ti
      plasmid of Agrobacterium tumefaciens.
AB  - The promoter of the 780 gene of T-right [Thomashow, M., Nutter, R., Montoya, A.,
      Gordon, M. & Nester, E. (1980) Cell 19, 729-739] from Agrobacterium tumefaciens
      Ti plasmid (pTi15955) was shown to contain an upstream cis-acting element
      (activator) having enhancer-like properties. To characterize the properties of
      this promoter element, it was placed in both polarities, upstream and downstream
      of a Delta-37 deletion mutant of the 780 gene. The Delta-37 deletion contains the
      entire 780 gene with the 5' flanking sequences deleted upstream of TATA to -37.
      The effect of the activator on in vivo transcriptional activity was assessed by
      S1 nuclease mapping utilizing a homologous reference gene as an internal
      standard. Transcript levels from sunflower crown gall tumors were between 127%
      and 90% of the wild-type 780 gene depending on the polarity of the activator
      element when placed directly upstream to the 780 gene Delta-37 promoter.
      Repositioning the activator element 613 base pairs further upstream increased
      transcription by 2-fold regardless of polarity. However, the activator element
      did not promote transcription when placed in either polarity approximately 200
      base pairs downstream of the poly(A) addition site. Upstream promoter fragments
      (TATA-distal) from the octopine synthase (ocs) and agropine synthase (ags) genes
      were also tested for activation of the Delta-37 construction. The ocs sequences
      activated transcription of the Delta-37 deletion to 14% of wild-type levels when
      placed upstream in the B (reverse) orientation. All other constructions with the
      ocs and ags sequences showed no enhancement of promoter activity.

PMID- 16593944
TI  - Control of pollen hydration in Brassica requires continued protein synthesis, and
      glycosylation in necessary for intraspecific incompatibility.
AB  - Pollen hydration and self-incompatibility (SI) in Brassica have been studied by
      using a combination of in vivo video-microscopy and experiments with metabolic
      inhibitors. Experiments with cycloheximide confirm earlier observations that
      pollen hydration is regulated through protein synthesis. No protein or
      glycoprotein has positively been identified with this event; however, it is
      unlikely that the total pool of any particular glycoprotein is involved, but
      rather a newly synthesized or otherwise activated fraction. Micromanipulation of
      pollen on the stigmatic papillae suggests that access to this hydration
      regulation system is limited to members of the Brassicaceae: pollen grains of
      other species-even those possessing dry stigmas-fail to hydrate. It is proposed
      that an interaction between enzymes of the stigma surface and the superficial
      layer of the pollen grain coating creates continuity between the content of the
      papillar wall and the grain protoplast. Inhibition of protein synthesis also
      overcomes SI, and since the advent of regulated hydration and synthesis of the so
      called S-gene glycoproteins coincide with the acquisition of the SI system, there
      is strong circumstantial evidence that the same molecular species is involved in
      both processes. Experiments with tunicamycin, which prevents glycosylation of
      glycoproteins, indicate that the glycosyl groups of the S-gene glycoprotein are
      required for the operation of the SI system but not for the regulation of
      hydration. Further experiments suggest that pollen is positively inhibited on
      incompatible papillae but that this inhibition is biostatic. Recovery from the
      effects of the SI system appears to involve the metabolism of an inhibitor by the
      pollen. SI in Brassica thus emerges as a sophisticated process under dynamic
      control in both the female and male partners. The evolutionary advantages of such
      a system are discussed.

PMID- 16593945
TI  - Social plasticity and early-diapausing females in a primitively social bee.
AB  - Many of the females of the first summer brood of the sweat bee Halictus
      rubicundus mate, soon vanish from the nesting site, undergo diapause, and return
      unworn the following spring to found their own nests without ever functioning as
      workers. Roughly half a season's foundresses may originate in this way. This
      finding contradicts previous assumptions regarding timing of reproductive
      production in sweat bees and offers a remarkable example of intraspecific social
      diversity; some females in the population behave as solitary bees while others
      are social. Such behavior may be widespread in bees and wasps, for it is almost
      undetectable with ordinary field techniques. These findings require the
      reevaluation of previous studies of sweat bee life cycles and of theories and
      models of the evolution of primitive insect societies.

PMID- 16593946
TI  - Water-borne stimuli released by predatory crabs and damaged prey induce more
      predator-resistant shells in a marine gastropod.
AB  - Individuals of the morphologically variable, rocky intertidal gastropod Thais (or
      Nucella) lamellosa developed larger apertural teeth when held in the presence of
      the predatory crab Cancer productus than when held in its absence, regardless of
      whether snails were fed or not. In addition, among fed snails larger apertural
      teeth were produced in the presence of crabs fed conspecific snails than in the
      presence of crabs fed frozen fish. Because all snails were held in containers
      through which water flowed from physically separated aquaria holding the crabs,
      these results indicate that water-soluble chemical cues released by this
      predatory crab and by damaged conspecifics induced T. lamellosa to improve the
      defense effectiveness of their shells. Finally, when allowed access to food,
      snails exposed to these stimuli ate fewer barnacles and grew less than those in
      the controls.

PMID- 16593947
TI  - Collective cues as a basis for nestmate recognition in polygynous leptothoracine
      ants.
AB  - Three alternative hypotheses have been advanced to explain the dynamics of
      individually produced nestmate-recognition cues in colonies of social insects:
      (i) that there is no effective transfer of cues among nestmates (individual
      hypothesis); (ii) that cues are shared reciprocally among nestmates (collective
      hypothesis); and (iii) that cues derived from the queen are transferred to all
      colony members and dominate all other cues in nestmate recognition (queen
      hypothesis). In the present study, a bioassay based on aggression by laboratory
      colonies toward workers introduced into their nests was used in conjunction with
      isolation and interspecific-adoption experiments to test these hypotheses for
      colonies of two closely related, polygynous, and polydomous ant species,
      Leptothorax ambiguus and Leptothorax longispinosus. The results provide strong
      evidence for the collective hypothesis. A collective system has long been
      postulated as one of the primary modes of nestmate discrimination among social
      insects but to my knowledge has never before been clearly demonstrated.

PMID- 16593948
TI  - Additional evidence from x-ray powder diffraction patterns that icosahedral quasi
      crystals of intermetallic compounds are twinned cubic crystals.
AB  - Analysis of the measured values of Q for the weak peaks (small maxima, usually
      considered to be background fluctuations, "noise") on the x-ray powder
      diffraction curves for 17 rapidly quenched alloys leads directly to the
      conclusion that they are formed by an 820-atom or 1012-atom primitive cubic
      structure that by icosahedral twinning produces the so-called icosahedral quasi
      crystals.

PMID- 16593949
TI  - Sporadicity: Between periodic and chaotic dynamical behaviors.
AB  - We define the class of sporadic dynamical systems as the systems where the
      algorithmic complexity of Kolmogorov [Kolmogorov, A. N. (1983) Russ. Math. Surv.
      38, 29-40] and Chaitin [Chaitin, G. J. (1987) Algorithmic Information Theory
      (Cambridge Univ. Press, Cambridge, U.K.)] as well as the logarithm of separation
      of initially nearby trajectories grow as n(v(0) )(log n)(v(1) ) with 0 < v(0) < 1
      or v(0) = 1 and v(1) < 0 as time n --> infinity. These systems present a behavior
      intermediate between the multiperiodic (v(0) = 0, v(1) = 1) and the chaotic ones
      (v(0) = 1, v(1) = 0). We show that intermittent systems of Manneville
      [Manneville, P. (1980) J. Phys. (Paris) 41, 1235-1243] as well as some countable
      Markov chains may be sporadic and, furthermore, that the dynamical fluctuations
      of these systems may be of Levy's type rather than Gaussian.

PMID- 16593950
TI  - Gap-modulation infrared spectroscopy of high transition temperature
      superconductors.
AB  - Conventional methods of determining the coupling factor alpha(2)(omega)F(omega)
      for the newly discovered high transition temperature (T(c)) cuprate
      superconductors by using tunneling and infrared measurements have thus far failed
      to show the cause of the very high T(c) of these compounds. This is due in part
      to difficulties in sample preparation for tunneling studies and to difficulties
      in obtaining good data at relatively high tunneling voltages. Also, in IR
      (infrared) measurements, small differences in absorptivity between the normal and
      superconducting state can be masked by changes in the phonon occupation at high
      and low temperatures. Here we propose a technique for determing the coupling
      constant, which should be less dependent on the surface quality of the sample
      than with tunneling and should allow measurements at higher energies with greater
      precision than do tunneling or simple IR observations. This should make possible
      a definitive determination of any possible exciton contribution to this coupling
      term, which would appear at energies well above the range where conventional IR
      or tunneling measurements are effective.

PMID- 16593951
TI  - Elimination of the adverse effects of urea fertilizer on seed germination,
      seedling growth, and early plant growth in soil.
AB  - The rapidly increasing importance of urea fertilizer in world agriculture has
      stimulated research to find methods of reducing the problems associated with the
      use of this fertilizer. One of these problems is that urea has adverse effects on
      seed germination, seedling growth, and early plant growth in soil. Because there
      is evidence that these adverse effects are caused largely, if not entirely, by
      ammonia produced through hydrolysis of urea fertilizer by soil urease, we
      explored the possibility that they could be reduced or eliminated by amending
      urea fertilizer with a small amount of a urease inhibitor. Studies with seeds of
      alfalfa (Medicago sativa L.), barley (Hordeum vulgare L.), oats (Avena sativa
      L.), rye (Secale cereale L.), sorghum [Sorghum bicolor (L.) Moench], and wheat
      (Triticum aestivum L.) showed that phenylphosphorodiamidate and N-(n
      butyl)thiophosphoric triamide were the most effective of 10 urease inhibitors
      evaluated for reduction of the adverse effect of urea on seed germination. N-(n
      butyl)-thiophosphoric triamide was superior to phenylphosphorodiamidate for
      reducing the adverse effects of urea solutions on seed germination and seedling
      growth in soil, and it completely eliminated the adverse effect of urea granules
      on early plant growth in soil. The data reported indicate that the adverse
      effects of urea fertilizer on seed germination, seedling growth, and early plant
      growth in soil could be eliminated or markedly reduced by amending the fertilizer
      with as little as 0.01% (wt/wt) of N-(n-butyl)thiophosphoric triamide.

PMID- 16593952
TI  - Pulsed photoacoustic detection of flash-induced oxygen evolution from intact
      leaves and its oscillations.
AB  - Photoacoustic signals from intact leaves, produced upon excitation with single
      turnover flashes, were shown to be dependent on their position in the flash
      sequence. Compared to the signal obtained from the first flash, all the others
      were time-shifted and had increased amplitudes. The signal from the third flash
      had the largest deviation, whereas that from the second flash deviated only
      minimally. The amplitude difference of the signals relative to that from the
      first flash was measured at a convenient time point (5 ms) and showed
      oscillations of period 4, similar to the O(2)-evolution pattern from algae. These
      oscillations were strongly damped, tending to a steady state from about the
      seventh flash on. The extra photoacoustic signal (relative to the first flash)
      was shown to be inhibited by 3-(3,4-dichlorophenyl)-1,1-dimethylurea, heat
      treatment, or water infiltration. Its change with flash number, its saturation
      with increasing flash energy, and the above inhibition criteria indicate that it
      originates in pulsed O(2) evolution. The sound wave produced by the first flash,
      however, arose by a photothermal mechanism only, as shown by its linear
      dependence on the flash intensity and insensitivity to the above treatments. The
      above flash pattern demonstrates that the photocycle of the S states (i.e.,
      positive charge accumulation before two water molecules can be oxidized in a
      concerted way to produce molecular oxygen) occurs in intact leaves. It proves the
      applicability of the photoacoustic method for mechanistic studies of O(2)
      evolution in leaves under physiological conditions. Water content of leaves is
      readily measured by this method.

PMID- 16593953
TI  - Standard energy metabolism of a desert harvester ant, Pogonomyrmex rugosus:
      Effects of temperature, body mass, group size, and humidity.
AB  - Pogonomyrmex rugosus (Hymenoptera: Formicidae) is an important seed predator in
      the Mojave Desert of the southwestern United States. Its standard rate of O(2)
      consumption ( Vo(2)) varied significantly with temperature ( Vo(2) = 10((-1.588 +
      0.0315T)), where Vo(2) is ml.g(-1).hr(-1) and T is body temperature in degrees
      C). The ratio of the Vo(2) values at 10 degrees C increments in body temperature,
      Q(10), also varied with temperature; methods of calculating Vo(2) from
      temperature with a shifting Q(10) are described. Vo(2) also varied with body mass
      ( Vo(2) = 0.0462M(0.669), where Vo(2) is ml.hr(-1) and M is body mass in g).
      Vo(2) was inversely related to relative humidity and was independent of group
      size. The rise in Vo(2) at low relative humidities was caused by increased
      activity and resulted in higher rates of net water loss. The primary metabolic
      adaptation to xeric conditions in P. rugosus appears to be a lower-than-predicted
      metabolic rate.

PMID- 16593954
TI  - Modular invariant representations of infinite-dimensional Lie algebras and
      superalgebras.
AB  - In this paper, we launch a program to describe and classify modular invariant
      representations of infinite-dimensional Lie algebras and superalgebras. We prove
      a character formula for a large class of highest weight representations L(lambda)
      of a Kac-Moody algebra [unk] with a symmetrizable Cartan matrix, generalizing the
      Weyl-Kac character formula [Kac, V. G. (1974) Funct. Anal. Appl. 8, 68-70]. In
      the case of an affine [unk], this class includes modular invariant
      representations of arbitrary rational level m = t/u, where t [unk] Z and u [unk]
      N are relatively prime and m + g >/= g/u (g is the dual Coxeter number). We write
      the characters of these representations in terms of theta functions and calculate
      their asymptotics, generalizing the results of Kac and Peterson [Kac, V. G. &
      Peterson, D. H. (1984) Adv. Math. 53, 125-264] and of Kac and Wakimoto [Kac, V.
      G. & Wakimoto, M. (1988) Adv. Math. 70, 156-234] for the u = 1 (integrable) case.
      We work out in detail the case [unk] = A(1) ((1)), in particular classifying all
      its modular invariant representations. Furthermore, we show that the modular
      invariant representations of the Virasoro algebra Vir are precisely the "minimal
      series" of Belavin et al. [Belavin, A. A., Polyakov, A. M. & Zamolodchikov, A. B.
      (1984) Nucl. Phys. B 241, 333-380] using the character formulas of Feigin and
      Fuchs [Feigin, B. L. & Fuchs, D. B. (1984) Lect. Notes Math. 1060, 230-245]. We
      show that tensoring the basic representation and modular invariant
      representations of A(1) ((1)) produces all modular invariant representations of
      Vir generalizing the results of Goddard et al. [Goddard P., Kent, A. & Olive, D.
      (1986) Commun. Math. Phys. 103, 105-119] and of Kac and Wakimoto [Kac, V. G. &
      Wakimoto, M. (1986) Lect. Notes Phys. 261, 345-371] in the unitary case. We study
      the general branching functions as well. All these results are generalized to the
      Kac-Moody superalgebras introduced by Kac [Kac, V. G. (1978) Adv. Math. 30, 85
      136] and to N = 1 super Virasoro algebras. We work out in detail the case of the
      superalgebra B(0, 1)((1)), showing, in particular, that restricting to its even
      part produces again all modular invariant representations of Vir. These results
      lead to general conjectures about asymptotic behavior of positive energy
      representations and classification of modular invariant representations.

PMID- 16593955
TI  - Lipid requirement and kinetic studies of solubilized UDP-galactose:diacylglycerol
      galactosyltransferase activity from spinach chloroplast envelope membranes.
AB  - We have demonstrated a lipid requirement for the UDPgalactose:1,2-diacylglycerol
      3-beta-D-galactosyl-transferase (or monogalactosyldiacylglycerol synthase; EC
      2.4.1.46), an enzyme involved in the biosynthesis of
      monogalactosyldiacylglycerol, solubilized from chloroplast envelope membranes and
      partially purified by hydroxyapatite chromatography. The enzyme fraction was
      highly delipidated (<0.1 mg of lipid per mg of protein), and addition of lipids
      extracted from chloroplast membranes was necessary to reveal the activity. Acidic
      glycerolipids, and especially phosphatidylglycerol, were the best activators of
      the enzyme. The preparation of a delipidated enzyme fraction and the development
      of optimal assay conditions were prerequisites for the determination of the
      kinetic parameters for the hydrophobic substrate of the enzyme, diacylglycerol.
      In addition, we have demonstrated the existence of two substrate-binding sites: a
      hydrophobic one for diacylglycerol and a hydrophilic one for UDP-galactose.

PMID- 16593956
TI  - Extremely large and slowly processed precursors to the Euglena light-harvesting
      chlorophyll a/b binding proteins of photosystem II.
AB  - Antibody to the Euglena light-harvesting chlorophyll a/b binding protein of
      photosystem II (LHCPII) immunoprecipitated 207-, 161-, 122-, and 110-kDa proteins
      from total Euglena proteins pulse-labeled for 10 min with [(35)S]sulfate. The
      25.6- and 27.2-kDa LHCPII were barely detectable in the immunoprecipitate. During
      a 40-min chase with unlabeled sulfate, the amount of radioactivity in the high
      molecular mass proteins decreased, and the amount of radioactivity in the 25.6-
      and 27.2-kDa LHCPII increased with kinetics consistent with a precursor-product
      relationship. The half-life of the high molecular mass proteins was approximately
      20 min. The major proteins immunoprecipitated from a nuclease-treated rabbit
      reticulocyte cell-free translation system programmed with Euglena whole cell or
      poly(A)(+) RNA had molecular masses corresponding to the molecular masses of the
      proteins immunoprecipitated from the pulse-labeled in vivo translation products.
      RNAs of 6.6 and 8.3 kilobases were the only Euglena whole cell and poly(A)(+)
      RNAs that hybridized to a 0.7-kilobase EcoRI-BamHI fragment of plasmid pAB165,
      which contains a portion of the coding sequence for Arabidopsis LHCPII. RNAs of
      this size are more than sufficient to code for proteins of 207 kDa. Taken
      together, these findings demonstrate that the LHCPIIs of Euglena are initially
      synthesized as slowly processed precursors with molecular masses of 207, 161,
      122, and 110 kDa.

PMID- 16593958
TI  - Path integration in desert ants, Cataglyphis fortis.
AB  - Foraging desert ants, Cataglyphis fortis, continually keep track of their own
      posotions relative to home- i.e., integrate their tortuous outbound routes and
      return home along straight (inbound) routes. By experimentally manipulating the
      ants' outbound trajectories we show that the ants solve this path integration
      problem not by performing a true vector summation (as a human navigator does) but
      by employing a computationally simple approximation. This approximation is
      characterized by small, but systematic, navigational errors that helped us
      elucidate the ant's way of computing its mean home vector.

PMID- 16593957
TI  - Cytokinin gene fused with a strong promoter enhances shoot organogenesis and
      zeatin levels in transformed plant cells.
AB  - The isopentenyltransferase (ipt) gene associated with cytokinin biosynthesis in
      plants was cloned from a tumor-inducing plasmid carried by Agrobacterium
      tumefaciens and placed under the control of promoters of differing activities,
      the cauliflower mosaic virus 35S promoter and the nopaline synthase promoter.
      These promoter-gene constructs were introduced into wounded Nicotiana stems, leaf
      pieces, and cucumber seedlings by A. tumefaciens infection. Shoots were observed
      in the infection site on all responding genotypes of Nicotiana plants infected
      with the 35S promoter construct (35S-ipt), whereas only 41% responded similarly
      to infection with the unmodified gene. Furthermore, shoots were observed 19 days
      after infection with the 35S-ipt gene but not until 28 to 45 days with the
      unaltered ipt gene. Shoots were more numerous (>40) on galls incited by 35S-ipt
      and were up to 6 times taller than shoots induced by the native gene. On Cucumis
      (cucumber), shoots were observed only on galls incited by the 35S-ipt construct.
      These galls were on the average 7.5 times larger than those incited by the
      nopaline synthase promoter construct (NOS-ipt) or the unmodified ipt gene. Zeatin
      and zeatinriboside concentrations averaged 23 times greater in the 35S-ipt
      transformed shoots than in ones transformed with the native ipt gene. These
      results suggest that a more active promoter on the ipt gene can enhance or change
      the morphogenic potential of transformed plant cells by increasing their
      endogenous cytokinin levels.

PMID- 16593959
TI  - Derivation of force fields for molecular mechanics and dynamics from ab initio
      energy surfaces.
AB  - We present a technique for addressing the problem of deriving potential energy
      functions for the simulation of organic, polymeric, and biopolymeric systems, as
      well as for modeling vibrational spectroscopic properties. This method is
      designed to address three major objectives: deriving and comparing optimal
      functional forms for describing the energies of molecular deformations and
      interactions, developing a technique to rapidly and objectively determine
      reasonable force constants for intermolecular and intramolecular interactions,
      and determining the transferability of these potential forms and constants. The
      first two of these objectives are addressed in this paper, while the latter
      problem will be treated elsewhere. The technique uses ab initio molecular energy
      surfaces, which are described by the energy and its first and second derivatives
      with respect to coordinates. As an example, application to a small model compound
      (i.e., the formate anion) is given. A variety of analytical forms for the
      potential are tested against the data, to find which forms are best. The
      importance of anharmonicity and cross terms in accounting for structure and
      energy, as well as for dynamics, is demonstrated and a more accurate
      representation of the out-of-plane deformation for a trigonal center is derived
      from the energy surfaces.

PMID- 16593960
TI  - Compact isospectral sets of plane domains.
AB  - Any isospectral family of two-dimensional Euclidean domains is shown to be
      compact in the C(infinity) topology. Previously Melrose, using heat invariants,
      was able to establish the C(infinity) compactness of the curvature of the
      boundary curves. The additional ingredient used in this paper to obtain the
      compactness of the domains is the behavior of the determinant of the Laplacian
      near the boundary of the moduli space.

PMID- 16593961
TI  - Homotopy invariance of eta-invariants.
AB  - Intersection homology and results related to the higher signature problem are
      applied to show that certain combinations of eta-invariants of the signature
      operator are homotopy invariant in various circumstances.

PMID- 16593962
TI  - Climate and red spruce growth and decline in the northern Appalachians.
AB  - Between the mid-1960s and mid-1980s, red spruce (Picea rubens Sarg.) died at
      unusual rates on the mountains of New York and western New England. We determined
      the relationship between standardized tree ring widths and monthly climate data
      for calibration and verification periods from 1856 to 1981 and found that after
      about 1960, there was a distinct shift in the temperature variables related to
      standardized ring widths in vigorous spruce. The beginning of widespread spruce
      mortality, regionwide growth decreases, and the shift in response to climate in
      the early 1960s corresponds to the onset of a decade of unusually cold winters
      and several consecutive years when severe winter damage was noted across the
      Northeast in this species. We suggest that the episodes of winter damage are an
      important initiating and synchronizing factor in the red spruce decline.

PMID- 16593963
TI  - Relevance of the reaction of a manganese(III) chelate with hydroxide ion to
      photosynthesis: Reaction of hydroxide ion with 5,10,15,20-tetrakis(2,4,6
      trimethylphenyl)porphinatomanganese(III) in ligating and nonligating solvents.
AB  - The reaction of HO(-) with 5,10,15,20-tetrakis(2,4,6
      trimethylphenyl)porphinatomanganese(III) chloride [(TMP)Mn(III)(Cl)] in ligating
      solvents (CH(3)CN, dimethyl sulfoxide, pyridine) results in formation of
      (TMP)Mn(II) ( approximately 10(6) M(-1).s(-r)), which in a slower reaction is
      converted to a product whose structure is suggested to be that of a porphyrin
      manganese(III) peroxo dimer. Admittance of O(2) at any time during these
      reactions leads to formation of the manganese(III) peroxide (TMP)Mn(III)(O(2))(
      ). In nonligating solvents [CH(2)Cl(2), (CH(3))(2)CO], the reaction of HO(-) with
      (TMP)Mn(III)(Cl) yields (TMP)Mn(IV)(OH)(2).

PMID- 16593964
TI  - Agrobacterium tumefaciens-mediated transformation of Arabidopsis thaliana root
      explants by using kanamycin selection.
AB  - Culture conditions were developed that induce Arabidopsis thaliana (L.) Heynh.
      root cuttings to regenerate shoots rapidly and at 100% efficiency. The shoots
      produce viable seeds in vitro or after rooting in soil. A transformation
      procedure for Arabidopsis root explants based on kanamycin selection was
      established. By using this regeneration procedure and an Agrobacterium tumor
      inducing Ti plasmid carrying a chimeric neomycin phosphotransferase II gene
      (neo), transformed seed-producing plants were obtained with an efficiency between
      20% and 80% within 3 months after gene transfer. F(1) seedlings of these
      transformants showed Mendelian segregation of the kanamycin-resistance trait. The
      transformation method could be applied to three different Arabidopsis ecotypes.
      In addition to the neo gene, a chimeric bar gene conferring resistance to the
      herbicide Basta was introduced into Arabidopsis. The expression of the bar gene
      was shown by enzymatic assay.

PMID- 16593965
TI  - Evidence for N- and C-terminal processing of a plant defense-related enzyme:
      Primary structure of tobacco prepro-beta-1,3-glucanase.
AB  - Tobacco glucan endo-1,3-beta-glucosidase (beta-1,3-glucanase; 1,3-beta-D-glucan
      glucanohydrolase; EC 3.2.1.39) exhibits complex hormonal and developmental
      regulation and is induced when plants are infected with pathogens. We determined
      the primary structure of this enzyme from the nucleotide sequence of five partial
      cDNA clones and the amino acid sequence of five peptides covering a total of 70
      residues. beta-1,3-Glucanase is produced as a 359-residue preproenzyme with an N
      terminal hydrophobic signal peptide of 21 residues and a C-terminal extension of
      22 residues containing a putative N-glycosylation site. The results of pulse
      chase experiments with tunicamycin provide evidence that the first step in
      processing is loss of the signal peptide and addition of an oligosaccharide side
      chain. The glycosylated intermediate is further processed with the loss of the
      oligosaccharide side chain and C-terminal extension to give the mature enzyme.
      Heterogeneity in the sequences of cDNA clones and of mature protein and in
      Southern blot analysis of restriction endonuclease fragments indicates that
      tobacco beta-1,3-glucanase is encoded by a small gene family. Two or three
      members of this family appear to have their evolutionary origin in each of the
      progenitors of tobacco, Nicotiana sylvestris and Nicotiana tomentosiformis.

PMID- 16593966
TI  - Self-incompatibility genes of Brassica oleracea: Expression, isolation, and
      structure.
AB  - We demonstrate by in situ hybridization the cell-type-specific expression of
      transcripts encoded by the self-incompatibility (S) locus of Brassica oleracea.
      These transcripts are not detected early in stigma development, their expression
      is switched on in the papillar cells of the stigma surface, and their levels
      increase in these cells in correlation with the acquisition by the stigma of the
      self-incompatibility response. By using a probe derived from the untranslated
      sequences at the 3' end of S cDNA, an S-gene copy expressed in the papillar cells
      has been isolated from among the multiple S-related copies that occur in the
      Brassica genome. Structural analysis of this gene shows that it lacks introns. In
      light of the strict spatial and temporal regulation of S-gene expression in
      precisely the cells that constitute the barrier to self-pollination, the self
      incompatibility response may be viewed as a cell-cell interaction between one
      pollen grain and one papillar cell.

PMID- 16593967
TI  - Colonization of America by Drosophila subobscura: Experiment in natural
      populations that supports the adaptive role of chromosomal-inversion
      polymorphism.
AB  - North America and South America have recently been colonized by the Palearctic
      species Drosophila subobscura. This double colonization offers a rare opportunity
      for evolutionary studies. Correlations between chromosomal arrangement
      frequencies and latitude were calculated for the colonizing populations. Signs of
      these correlations are highly coincident with those found in the Old World. These
      results provide experimental support for the adaptive value of the chromosomal
      inversion polymorphism; historical and other nonadaptive explanations are thus
      excluded or relegated to a secondary role.

PMID- 16593968
TI  - Allopolyploidy in bryophytes: Multiple origins of Plagiomnium medium.
AB  - Bryophytes are thought to be unique among land plants in lacking the important
      evolutionary process of allopolyploidy, which involves interspecific
      hybridization and chromosome doubling. Electrophoretic data show, however, that
      the polyploid moss Plagiomnium medium is an allopolyploid derivative of
      Plagiomnium ellipticum and Plagiomnium insigne, that P. medium has originated
      more than once from these progenitors, and that cross-fertilization results in
      interlocus genetic recombination. Evidence from restriction fragment length
      polymorphisms in chloroplast DNA implicates P. insigne as the female parent in
      interspecific hybridizations with P. ellipticum. Contrary to prevailing views, it
      appears that those evolutionary processes responsible for genetic differentiation
      and speciation in other land plants occur in the bryophytes as well.

PMID- 16593969
TI  - Conformational analysis of 9beta,19-cyclopropyl sterols: Detection of the
      pseudoplanar conformer by nuclear Overhauser effects and its functional
      implications.
AB  - Nuclear Overhauser difference spectroscopy and variable temperature studies of
      the 9beta,19-cyclopropyl sterols 24,25-dehydropollinastanol (4,4-desmethyl-5alpha
      cycloart-24-en-3beta-ol) and cyclolaudenol [(24S)-24-methyl-5alpha-cycloart
      25(27)-en-3beta-ol] have shown the solution conformation of the B/C rings to be
      twist-chair/twist-boat rather than boat/chair as suggested in the literature.
      This is very similar to the known crystal structure conformation of 9beta,19
      cyclopropyl sterols. The effect of these conformations on the molecular shape is
      highly significant: the first conformation orients into a pseudoplanar or flat
      shape analogous to lanosterol, whereas the latter conformation exhibits a bent
      shape. The results are interpreted to imply that, for conformational reasons,
      cyclopropyl sterols can be expected to maintain the pseudoplanar shape in
      membrane bilayers.

PMID- 16593970
TI  - Binding of the phytotoxin zinniol stimulates the entry of calcium into plant
      protoplasts.
AB  - Zinniol [1,2-bis(hydroxymethyl)-3-methoxy-4-methyl-5-(3-methyl-2
      butenyloxy)benzene], a toxin produced by fungi of the Alternaria group, causes
      symptoms in plants that resemble those induced by the fungi. The phytotoxin binds
      to carrot protoplasts and isolated membranes in a saturable and reversible
      manner. Receptor occupancy stimulates entry of calcium into protoplasts. Zinniol
      can partially reverse the effects and binding of the calcium-channel blockers
      desmethoxyverapamil and bepridil. Selected cell lines that are insensitive to
      zinniol lose part of their binding capacity and sensitivity to the action of the
      agonist-like compound but are still able to bind calcium-channel blockers. We
      conclude that zinniol acts on calcium entry but that the targets of the toxin and
      of calcium-channel blockers are dissimilar, suggesting the occurrence of sites
      affected both by zinniol and by channel blockers and of sites affected only by
      zinniol.

PMID- 16593971
TI  - Global change: Geographical approaches (A Review).
AB  - The International Geosphere Biosphere Program sponsored by the International
      Council of Scientific Unions is directing attention to geophysical and biological
      change as influenced by human modifications in global energy and mass exchanges.
      Geographers in the Soviet Union and the United States have joined in critical
      appraisal of their experience in studying environmental change. This initial
      report is on some promising approaches, such as the reconstruction of earlier
      landscape processes, modeling of the dynamics of present-day landscapes, analysis
      of causes and consequences of anthropogenic changes in specified regions,
      appraisal of social response to change, and enhanced geographic information
      systems supported by detailed site studies.

PMID- 16593972
TI  - Mobility of P elements in drosophilids and nondrosophilids.
AB  - The mobility properties of the Drosophila melanogaster P element in drosophilid
      and nondrosophilid species has been determined using a P-element mobility assay
      that is conducted transiently in insect embryos. P elements are mobilizable in
      all drosophilids tested, including species outside the genus Drosophila but not
      in the related Tephritidae (order: Diptera), although the P-element gene
      necessary for mobility, transposase, is transcribed. These results show that
      without modifications P elements will not serve as general insect gene vectors
      and suggest that nonconserved host-encoded factors participate in the
      transposition of P elements. Our methods will be generally useful for analyzing
      the cis- and trans-acting factors required for P-element mobility in vivo and
      could be used to analyze the mobility properties of other transposable elements
      in insects.

PMID- 16593973
TI  - Independent photocycles of the spectrally distinct forms of bacteriorhodopsin.
AB  - Time-resolved, flash-induced difference absorbance spectra (300-700 nm) at pH
      10.5 and 5 degrees C for the bacteriorhodopsin photocycle fast and slow decaying
      forms of the M intermediate (M(f) and M(s), respectively) and R intermediate are
      reported. The main distinguishing features are as follows: For M(f), DeltaA(max)
      = 412 nm, a shoulder at 436 nm, no absorbance change at 350 nm; DeltaA(min) = 565
      nm; DeltaA(412)/DeltaA(565) = 0.85. For M(s), DeltaA(max) = 412 nm, a shoulder at
      386 nm; DeltaA(min) = 575 nm; DeltaA(412)/DeltaA(575) = 0.6. For R, DeltaA(max) =
      336 and 350 nm (double peak), smaller peaks at 386 and 412 nm; DeltaA(min) = 585
      nm; DeltaA(350)/DeltaA(585) = 0.2. The different difference spectra for M(f) and
      M(s) provide direct evidence that these species, initially identified by their
      kinetics, are physically distinct. With fast transient absorption spectroscopy,
      it was shown that R may form very fast, perhaps faster than the L intermediate
      decays. On the basis of the different bleaching peaks for M(f) and M(s), we
      propose that M(f) and M(s) are in independent photocycles formed from slightly
      different forms of bacteriorhodopsin. R may also be in a different photocycle.
      The different forms of bacteriorhodopsin are probably in dynamic equilibrium with
      their ratios, controlled by pH and temperature.

PMID- 16593974
TI  - Developmental regulation of embryonic genes in plants.
AB  - Somatic embryogenesis from cultured carrot cells progresses through successive
      morphogenetic stages termed globular, heart, and torpedo. To understand the
      molecular mechanisms underlying plant embryogenesis, we isolated two genes
      differentially expressed during embryo development. The expression of these two
      genes is associated with heart-stage embryogenesis. By altering the culture
      conditions and examining their expressions in a developmental variant cell line,
      we found that these genes were controlled by the developmental program of
      embryogenesis and were not directly regulated by 2,4-dichlorophenoxyacetic acid,
      the growth regulator that promotes unorganized growth of cultured cells and
      suppresses embryo morphogenesis. These genes are also expressed in carrot zygotic
      embryos but not in seedlings or mature plants.

PMID- 16593975
TI  - Conservation of gene repertoire but not gene order in pepper and tomato.
AB  - Homologies of tomato and pepper genes have been compared, and genetic linkage
      maps have been constructed based on a common set of cDNA clones and selected
      single-copy genomic clones. We report here that the gene repertoire of these two
      species is highly conserved, yet the linear order of the genes on the chromosomes
      has been greatly modified. Although the two species share the same number of
      centromeres, the chromosomal regions around those centromeres have undergone
      extensive rearrangements. Accompanying the extensive chromosome rearrangement has
      been a change in locus number for approximately 12% of the loci detected by
      random cDNA clones. Duplicated loci within each genome are normally found on
      different chromosomes and are not confined to one species, thus ruling out gene
      duplication as an explanation for the 4-fold higher DNA content of pepper. At
      least one of the duplications occurred since the divergence of tomato and pepper
      from their last common ancestor.

PMID- 16593976
TI  - The oldest fossil bee: Apoid history, evolutionary stasis, and antiquity of
      social behavior.
AB  - Trigona prisca, a stingless honey bee (Apidae; Meliponinae), is reported from
      Cretaceous New Jersey amber (96-74 million years before present). This is about
      twice the age of the oldest previously known fossil bee, although Trigona is one
      of the most derived bee genera. T. prisca is closely similar to modern
      neotropical species. Most of bee evolution probably occurred during the
      approximately 50 million years between the beginning of the Cretaceous when
      flowering plants (on which bees depend) appeared and the time of T. prisca. Since
      then, in this phyletic line of Meliponinae, there has been almost no
      morphological evolution. Since the fossil is a worker, social organization had
      arisen by its time.

PMID- 16593977
TI  - Photoreduction of carbon dioxide by aqueous ferrous ion: An alternative to the
      strongly reducing atmosphere for the chemical origin of life.
AB  - We have shown that ferrous ion at neutral pH photoreduces water to hydrogen with
      a high quantum yield on excitation with near-ultraviolet light. This simple
      system also efficiently reduces carbon dioxide (bicarbonate ions) to
      formaldehyde. Overall, these reactions offer a solution to a dilemma confronting
      the standard or Oparin-Urey model of the origin of life. If carbon dioxide was
      the main form of carbon on the primitive earth, the ferrous photoreaction would
      have provided the reduced carbon necessary to form amino acids and other
      biogenetic molecules. We believe this system may have been the progenitor to the
      biological photosynthetic systems.

PMID- 16593978
TI  - Projective determinacy.
AB  - It is shown that projective determinacy follows from large cardinal axioms weaker
      than the assertion that supercompact cardinals exist.

PMID- 16593979
TI  - Supercompact cardinals, sets of reals, and weakly homogeneous trees.
AB  - It is shown that if there exists a supercompact cardinal then every set of reals,
      which is an element of L(R), is the projection of a weakly homogeneous tree. As a
      consequence of this theorem and recent work of Martin and Steel [Martin, D. A. &
      Steel, J. R. (1988) Proc. Natl. Acad. Sci. USA 85, 6582-6586], it follows that
      (if there is a supercompact cardinal) every set of reals in L(R) is determined.

PMID- 16593980
TI  - Photosynthetic characteristics of an amphibious plant, Eleocharis vivipara:
      Expression of C(4) and C(3) modes in contrasting environments.
AB  - Eleocharis vivipara Link, a freshwater amphibious leafless plant belonging to the
      Cyperaceae can grow in both terrestrial and submersed aquatic conditions. Two
      forms of E. vivipara obtained from these contrasting environments were examined
      for the characteristics associated with C(4) and C(3) photosynthesis. In the
      terrestrial form (delta (13)C values = -13.5 to -15.4 per thousand, where per
      thousand is parts per thousand), the culms, which are photosynthetic organs,
      possess a Kranz-type anatomy typical of C(4) plants, and well-developed bundle
      sheath cells contain numerous large chloroplasts. In the submersed form (delta
      (13)C value = -25.9 per thousand), the culms possess anatomical features
      characteristic of submersed aquatic plants, and the reduced bundle-sheath cells
      contain only a few small chloroplasts. (14)C pulse-(12)C chase experiments showed
      that the terrestrial form and the submersed form fix carbon by way of the C(4)
      pathway, with aspartate (40%) and malate (35%) as the main primary products, and
      by way of the C(3) pathway, with 3-phosphoglyceric acid (53%) and sugar
      phosphates (14%) as the main primary products, respectively. The terrestrial form
      showed photosynthetic enzyme activities typical of the NAD-malic enzyme-C(4)
      subtype, whereas the submersed form showed decreased activities of key C(4)
      enzymes and an increased ribulose 1,5-bisphosphate carboxylase (EC 4.1.1.39)
      activity. These data suggest that this species can differentiate into the C(4)
      mode under terrestrial conditions and into the C(3) mode under submersed
      conditions.

PMID- 16593981
TI  - Glutathione and fungal elicitor regulation of a plant defense gene promoter in
      electroporated protoplasts.
AB  - To investigate the mechanisms underlying activation of plant defenses against
      microbial attack we have studied elicitor regulation of a chimeric gene
      comprising the 5' flanking region of a defense gene encoding the phytoalexin
      biosynthetic enzyme chalcone synthase fused to a bacterial chloramphenicol
      acetyltransferase gene. Glutathione or fungal elicitor caused a rapid, marked but
      transient expression of the chimeric gene electroporated into soybean
      protoplasts. The response closely resembled that of endogenous chalcone synthase
      genes in suspension cultured cells. Functional analysis of 5' deletions suggests
      that promoter activity is determined by an elicitor-regulated activator located
      between the "TATA box" and nucleotide position -173 and an upstream silencer
      between -173 and -326. These cis-acting elements function in the transduction of
      the elicitation signal to initiate elaboration of an inducible defense response.

PMID- 16593982
TI  - Characterization of a gene from a tomato pathogen determining hypersensitive
      resistance in non-host species and genetic analysis of this resistance in bean.
AB  - Xanthomonas campestris pv. vesicatoria is the causal agent of leaf spot disease
      on pepper and tomato. On non-host plants, such as bean, soybean, cowpea, alfalfa,
      and cotton, X. campestris pv. vesicatoria is unable to cause disease, inducing
      instead a hypersensitive resistance response (HR). Since avirulence genes from X.
      campestris pv. vesicatoria specifically induce HR in several pepper cultivars, we
      investigated whether there were avirulence genes governing induction of
      resistance in non-host species. We report on the molecular cloning and
      characterization of a non-host avirulence gene from X. campestris pv.
      vesicatoria. A cosmid clone isolated from a library of DNA from X. campestris pv.
      vesicatoria tomato race 1 converted X. campestris pv. phaseoli to avirulence by
      inducing HR on the bean cultivar Sprite, but not on Bush Blue Lake. The HR
      inducing activity was localized to a 2.1-kilobase Pst I fragment of DNA,
      designated avrRxv. In addition, we demonstrate that avrRxv inhibited disease
      production by several X. campestris pathovars on their normally susceptible
      hosts: glycines on soybean, vignicola on cowpea, alfalfae on alfalfa, holcicola
      on corn, and malvacearum on cotton. The HR resistance in bean induced by avrRxv
      segregated as a single incompletely dominant gene, designated Rxv. These results
      indicate that the avirulence gene avrRxv and the resistance gene Rxv partially
      control the outcome of the interaction between X. campestris pv. vesicatoria and
      the non-host bean.

PMID- 16593983
TI  - High-frequency mutations in a plasmid-encoded gas vesicle gene in Halobacterium
      halobium.
AB  - Gas vesicle-deficient mutants of Halobacterium halobium arise spontaneously at
      high frequency (about 1%). The mutants are readily detected, forming translucent
      colonies on agar plates in contrast to opaque wild-type colonies. To investigate
      the mechanism of this mutation, we recently cloned a plasmid-encoded gas vesicle
      protein gene, gvpA, from H. halobium. In the wild-type NRC-1 strain the gvpA gene
      is encoded by a multicopy plasmid of approximately 150 kilobase pairs (kb). We
      have now characterized 18 gas vesicle-deficient mutants and 4 revertants by
      phenotypic and Southern hybridization analyses. Our results indicate that the
      mutants fall into three major classes. Class I mutants are partially gas vesicle
      deficient (Vac(delta-)) and unstable, giving rise to completely gas vesicle
      deficient (Vac(-)) derivatives and Vac(+) revertants at frequencies of 1-5%. The
      restriction map of the gvpA gene region in class I mutants is unchanged but the
      gene copy number is reduced compared to the Vac(+) strains. Class II mutants can
      be either Vac(delta-) or completely Vac(-) but are relatively stable. They
      contain insertion sequences within or upstream of the gvpA gene. A Vac(-) class
      II mutant, R1, contains the 1.3-kb insertion sequence, ISH3, within the gvpA
      gene, whereas four Vac(delta-) class II mutants contain other insertion sequences
      upstream of the gene. Class III mutants are stable Vac(-) derivatives of either
      the wild-type or class I mutants and have no detectable copies of the gvpA gene.
      Based on these results, we discuss the mechanisms of gas vesicle mutations in H.
      halobium.

PMID- 16593984
TI  - Nonlinear saturation of ballooning modes in tokamaks and stellarators.
AB  - The spectral code BETAS computes plasma equilibrium in a toroidal magnetic field
      B = [unk]s x [unk]Psi with remarkable accuracy because the finite difference
      scheme employed in the radial direction allows for discontinuities of the flux
      function Psi across the nested surfaces s = const. Instability of higher modes in
      stellarators like the Heliotron E can be detected in roughly an hour on the best
      supercomputers by calculating bifurcated equilibria that are defined over just
      one field period. The method has been validated by comparing results about
      nonlinear saturation of ballooning modes in tokamaks with numerical data from the
      PEST code.

PMID- 16593985
TI  - Metastability transfer spectroscopy with two like ions in the same trap.
AB  - High-resolution optical spectroscopy of an individual trapped ion is hampered by
      lack of sharp lasers. This suggests the use of a second metastable excited ion as
      an ultrasharp light source. To this end, laser-cool two barium ions to an
      equilibrium distance of approximately 8 mum on the z (symmetry) axis of the trap
      and, in this (earth)(Ba(+))(2)-molecule, visually or photoelectrically identify
      them as A and B by their location. Briefly turn on a 455-nm spectral lamp until
      one of the ions, say the A ion, is pumped into the metastable D(5/2) level and
      turns invisible. Focus on the visible, spatially well-resolved B ion and turn off
      the blue and red illumination lasers for approximately 15 s. Then turn them back
      on again and check on whether the excitation by chance has been transferred to
      the B ion and is now in the D(5/2) level and dark while the A ion is bright. The
      cross section for absorption of the lambda(D(5/2) --> S(1/2)) identical with
      lambda(0) = 1.76 mum radiation by a stationary ion can be >lambda(0) (2)/2pi.
      Thus, by pushing the two ions together to approximately lambda(0)/4 by turning on
      a much stronger trapping field during the excitation exchange period, one might
      be able to detect excitation transfer in >10% of the attempts. The ions are tuned
      relative to each other by a 0- to 10-mV/cm variable dc field in the z direction,
      which displaces them axially and causes them to see different rf fields, which
      Stark-shifts their frequencies. In this way, a resonant transfer response as
      sharp as twice the natural width of the D(5/2) level, 11 mHz or a Q approximately
      0.4 x 10(17), might be demonstrated.

PMID- 16593986
TI  - Thermodynamics of cosmological matter creation.
AB  - A type of cosmological history that includes large-scale entropy production is
      proposed. These cosmologies are based on reinterpretation of the matter-energy
      stress tensor in Einstein's equations. This modifies the usual adiabatic energy
      conservation laws, thereby including irreversible matter creation. This creation
      corresponds to an irreversible energy flow from the gravitational field to the
      created matter constituents. This point of view results from consideration of the
      thermodynamics of open systems in the framework of cosmology. It is shown that
      the second law of thermodynamics requires that space-time transforms into matter,
      while the inverse transformation is forbidden. It appears that the usual initial
      singularity associated with the big bang is structurally unstable with respect to
      irreversible matter creation. The corresponding cosmological history therefore
      starts from an instability of the vacuum rather than from a singularity. This is
      exemplified in the framework of a simple phenomenological model that leads to a
      three-stage cosmology: the first drives the cosmological system from the initial
      instability to a de Sitter regime, and the last connects with the usual matter
      radiation Robertson-Walker universe. Matter as well as entropy creation occurs
      during the first two stages, while the third involves the traditional
      cosmological evolution. A remarkable fact is that the de Sitter stage appears to
      be an attractor independent of the initial fluctuation. This is also the case for
      all the physical predictions involving the present Robertson-Walker universe.
      Most results obtained previously, in the framework of quantum field theory, can
      now be obtained on a macroscopic basis. It is shown that this description leads
      quite naturally to the introduction of primeval black holes as the intermediate
      stage between the Minkowski vacuum and the present matter-radiation universe. The
      instability at the origin of the universe is the result of fluctuations of the
      vacuum in which black holes act as membranes that stabilize these fluctuations.
      In short, black holes will be produced by and "inverse" Hawking radiation process
      and, once formed, will decompose into "real" matter through the usual Hawking
      radiation. In this way, the irreversible transformation of space-time into matter
      can be described as a phase separation between matter and gravitation in which
      black holes play the role of "critical nuclei."

PMID- 16593987
TI  - Immunochemical localization of ribulose-1,5-bisphosphate carboxylase in the
      symbiont-containing gills of Solemya velum (Bivalvia: Mollusca).
AB  - The distribution of the Calvin cycle enzyme ribulose-1,5-bisphosphate carboxylase
      (RbuP(2)Case; EC 4.1.1.39) was examined by using two immunological methods in
      tissues of Solemya velum, an Atlantic coast bivalve containing putative
      chemoautotrophic symbionts. Antibodies elicited by the purified large subunit of
      RbuP(2)Case from tobacco (Nicotiana tabacum) cross-reacted on immunoblots with a
      protein of similar molecular mass occurring in extracts of the symbiont
      containing gill tissue of S. velum. No cross-reactivity was detected in symbiont
      free tissue extracts. The antiserum also cross-reacted in immunoblots with
      proteins of Thiobacillus neapolitanus, a free-living sulfuroxidizing
      chemoautotroph whose RbuP(2)Case has been well characterized. In protein A-gold
      immunoelectron microscopy studies, this antiserum consistently labeled the
      symbionts but not surrounding host gill tissue, indicating that the symbionts are
      responsible for the RbuP(2)Case activity.

PMID- 16593988
TI  - Light-mediated changes in two proteins found associated with plasma membrane
      fractions from pea stem sections.
AB  - Irradiation of etiolated pea (Pisum sativum L.) seedlings with white light
      affects two proteins, both of monomer molecular mass near 120 kDa. Both proteins
      have been detected in association with plasma membrane fractions. The first is
      identifiable in that it becomes heavily phosphorylated when the membranes are
      incubated with exogenous ATP. The second of these proteins is phytochrome, as
      determined by electrophoretic transfer (Western) blot analysis. Measurable
      phosphorylation and phytochrome (the latter detected by antigenicity) decline
      when the tissue is irradiated with white light prior to membrane isolation and in
      vitro phosphorylation. The phosphorylated protein is probably not phytochrome for
      three reasons. (i) It shows a slightly different distribution in sucrose
      gradients. (ii) Red light causes a gradual decline in the phytochrome that is
      associated with membrane fractions but has a negligible effect on the
      phosphorylatable protein; blue light, on the other hand, causes significantly
      slower loss of phytochrome than does red light but brings about a rapid decline
      in the phosphorylation signal. (iii) The molecular masses are not identical. The
      association of both proteins with membrane fractions is probably neither ionic
      nor, at least for the phosphorylatable protein, the consequence of entrapment of
      soluble proteins in vesicles formed during tissue extraction. Phytochrome is lost
      from the membrane fractions during irradiation, as judged by loss of
      antigenicity. Whether the phosphorylatable protein is lost, a specific kinase is
      lost, phosphatase activity increases, or phosphorylatable sites are blocked as a
      consequence of blue light treatment is not known.

PMID- 16593989
TI  - Maculosin, a host-specific phytotoxin for spotted knapweed from Alternaria
      alternata.
AB  - Several diketopiperazines have been isolated from liquid cultures of Alternaria
      alternata, the causal agent of black leaf blight of spotted knapweed, Centaurea
      maculosa Lam. One of these compounds, maculosin [the diketopiperazine cyclo(-L
      Pro-L-Tyr-)], was active in the nicked-leaf bioassay at 10(-5) M; synthetic
      maculosin possessed chemical and biological activities identical to those of the
      natural product. Other diketopiperazines isolated from the fungus possessed
      either less activity or none at all. In tests against 19 plant species, maculosin
      was phytotoxic only to spotted knapweed. Thus maculosin is a host-specific
      phytotoxin from a weed pathogen.

PMID- 16593990
TI  - Unified structure theory of icosahedral quasicrystals: Evidence from neutron
      powder diffraction patterns that AlCrFeMnSi, AlCuLiMg, and TiNiFeSi icosahedral
      quasicrystals are twins of cubic crystals containing about 820 or 1012 atoms in a
      primitive unit cube.
AB  - A unified structure theory of icosahedral quasicrystals, combining the twinned
      cubic-crystal theory and the Penrose-tiling-six-dimensional-projection theory, is
      described. Values of the primitive-cubic lattice constant for several
      quasicrystals are evaluated from x-ray and neutron diffraction data. The fact
      that the low-angle diffraction maxima can be indexed with cubic unit cells
      provides additional support for the twinned-cubic-crystal theory of icosahedral
      quasicrystals.

PMID- 16593991
TI  - Infrared spectroelectrochemistry of bacteriochlorophylls and bacteriopheophytins:
      Implications for the binding of the pigments in the reaction center from
      photosynthetic bacteria.
AB  - The IR spectra of the bacteriochlorophyll a and b cations and the
      bacteriopheophytin a and b anions were obtained by using an IR and optically
      transparent electrochemical cell. Prominent effects of radical formation on the
      vibrational spectra were found for bands assigned to the ester, keto, and acetyl
      C=O groups and for vibrations from macrocycle bonds. The (radical-minus-neutral)
      difference spectra are compared to the light-induced difference spectra of the
      primary donor photooxidation and the intermediary acceptor photoreduction in the
      reaction center of photosynthetic bacteria. Light-induced absorbance changes from
      bacteriochlorophyll a-containing reaction centers bear striking similarities to
      the electrochemically induced absorbance changes observed upon formation of
      bacteriochlorophyll a(+)in vitro. Comparison of the radical formation in vitro in
      a hydrogen-bonding or a nonhydrogen-bonding solvent suggests an ester C=O group
      hydrogen bonded in the neutral state but free in the cation state. For the keto
      C=O group, the same comparison indicates one free carbonyl group. The (anion
      minus-neutral) difference spectra of bacteriopheophytin a and b exhibit a single
      band in the ester C=O frequency range. In contrast, two bands are observed in the
      difference spectra of the intermediary acceptor reduction in the reaction center
      of Rhodopseudomonas viridis. The higher frequency band exhibits a sensitivity to
      (1)H-(2)H exchange, which suggests a contribution from a protonated carboxyl
      group of an amino acid side chain.

PMID- 16593992
TI  - Site-directed mutagenesis in photosystem II of the cyanobacterium Synechocystis
      sp. PCC 6803: Donor D is a tyrosine residue in the D2 protein.
AB  - The chemical nature of electron donor(s) in photosystem II in photosynthetic
      membranes was analyzed by site-directed mutagenesis of the gene encoding the
      protein D2 of the photosystem II reaction center. Mutation of the Tyr-160 residue
      of the D2 protein into phenylalanine results in the disappearance of the electron
      paramagnetic resonance signal II(S) originating from D(+), the oxidized form of
      the slow photosystem II electron donor D. Signal II(S) is still present if a
      neighboring residue in D2, Met-159, is mutated into arginine. Both mutants have
      normal rereduction kinetics of the oxidized primary electron donor, P680(+), in
      octyl glucoside-extracted thylakoids, indicating that D is not directly involved
      in P680(+) reduction. However, overall photosystem II activity appears to be
      impaired in the Tyr-160-Phe mutant: photosystem II-dependent growth of this
      mutant is slowed down by a factor of 3-4, whereas photoheterotrophic growth rates
      in wild type and mutant are essentially identical. Binding studies of diuron, a
      photosystem II herbicide, show that there is no appreciable decrease in the
      number of photosystem II centers in the Tyr-160-Phe mutant. The decrease in
      photosystem II activity in this mutant may be interpreted to indicate a role of D
      in photoactivation, rather than one as an important redox intermediate in the
      photosynthetic electron-transport chain.

PMID- 16593993
TI  - Stable genetic transformation of intact Nicotiana cells by the particle
      bombardment process.
AB  - We show that the genetic transformation of Nicotiana tabacum can be achieved by
      bombarding intact cells and tissues with DNA-coated particles. Leaves or
      suspension culture cells were treated with tungsten microprojectiles carrying
      plasmid DNA containing a neomycin phosphotransferase gene. Callus harboring the
      foreign gene was recovered from the bombarded tissue by selection on medium
      containing kanamycin. Kanamycin-resistant plants have subsequently been
      regenerated from the callus derived from leaves. Transient expression of an
      introduced beta-glucuronidase gene was used to assess the efficiency of DNA
      delivery by microprojectiles. The frequency of cells that were stably transformed
      with the neomycin phosphotransferase gene was a few percent of the cells that
      transiently expressed the beta-glucuronidase gene. These results show that gene
      transfer by high-velocity microprojectiles is a rapid and direct means for
      transforming intact plant cells and tissues that eliminates the need for
      production of protoplasts or infection by Agrobacterium.

PMID- 16593994
TI  - Rhizobium meliloti nodA and nodB genes are involved in generating compounds that
      stimulate mitosis of plant cells.
AB  - The nodB gene of Rhizobium meliloti encodes a 23.8-kDa protein that is conserved
      in several Rhizobium species. Monospecific polyclonal antibodies against NodB
      were used to localize this protein in the cytosol of R. meliloti and Escherichia
      coli cells containing nodABC genes. In comparison to the NodA and NodC proteins,
      NodB is synthesized in a disproportionately low amount. The NodA and NodB
      proteins are involved in generating small, heat-stable compounds that stimulate
      the mitosis of various plant protoplasts. Our experiments suggest that NodC is
      not involved in the synthesis of the factors. On the basis of their properties,
      we speculate that the factors are cytokinin-like substances.

PMID- 16593995
TI  - Comb wax mediates the acquisition of nest-mate recognition cues in honey bees.
AB  - Honey bees, Apis mellifera, acquire nest-mate recognition cues from wax, the
      predominant material used in nest construction. Exposure of a newly emerged
      worker bee to wax-comb substrate significantly reduced the acceptability of that
      worker to sister bees. Cues acquired from the comb provided colony-specific
      information about the identity of worker bees; moreover, the effect of comb
      exposure has been previously shown to override individually produced cues. Food
      odors (anise oil), when dissolved in paraffin wax, affected worker-recognition
      characteristics but food odors did not affect these characteristics when fed to
      bees in sugar candy. Paraffin wax alone did not affect the recognition cues of
      bees, showing that the wax can be a neutral medium for the transmission of cues.
      The wax comb in the colony and the hydrocarbon outer layer of the bee cuticle may
      be a continuous medium for any hydrocarbon-soluble substances used by honey bees
      in nest-mate recognition; if so, a mechanism by which environmental cues are
      acquired by honey bees is provided.

PMID- 16593996
TI  - Estimates for the partial differential-Neumann problem for pseudoconvex domains
      in C of finite type.
AB  - We outline results obtained for the partial differential-Neumann problem for an
      arbitrary pseudoconvex domain in C(2) of finite type. We obtain an approximation
      to the Neumann operator. A number of sharp estimates for the solution of partial
      differentialu = f are a consequence; one of these is an extension of the L(1)
      estimate of Henkin and Skoda used to characterize the zero sets of functions of
      the Nevanlinna class.

PMID- 16593997
TI  - Reduction of polygalacturonase activity in tomato fruit by antisense RNA.
AB  - Polygalacturonase [PG; poly(1,4-alpha-D-galacturonide) glycanhydrolase; EC
      3.2.1.15] is expressed in tomato only during the ripening stage of fruit
      development. PG becomes abundant during ripening and has a major role in cell
      wall degradation and fruit softening. Tomato plants were transformed to produce
      antisense RNA from a gene construct containing the cauliflower mosaic virus 35S
      promoter and a full-length PG cDNA in reverse orientation. The construct was
      integrated into the tomato genome by Agrobacterium-mediated transformation. The
      constitutive synthesis of PG antisense RNA in transgenic plants resulted in a
      substantial reduction in the levels of PG mRNA and enzymatic activity in ripening
      fruit. The steady-state levels of PG antisense RNA in green fruit of transgenic
      plants were lower than the levels of PG mRNA normally attained during ripening.
      However, analysis of transcription in isolated nuclei demonstrated that the
      antisense RNA construct was transcribed at a higher rate than the tomato PG
      gene(s). Analysis of fruit from transgenic plants demonstrated a reduction in PG
      mRNA and enzymatic activity of 70-90%. The reduction in PG activity did not
      prevent the accumulation of the red pigment lycopene.

PMID- 16593998
TI  - Identification of a unique isoform of 1-aminocyclopropane-1-carboxylic acid
      synthase by monoclonal antibody.
AB  - 1-Aminocyclopropane-1-carboxylic acid (ACC) synthase (EC 4.4.1.14) is a key
      enzyme regulating ethylene biosynthesis in higher plants. A monoclonal antibody
      (mAb T20C) that immunoprecipitates the ACC synthase activity from tomato pericarp
      tissue extracts revealed that mAb T20C immunodecorates an approximately 67-kDa
      polypeptide. On isoelectric focusing gels, ACC synthase activity in cell-free
      preparations was resolved into three distinct activity peaks with pI values 5.3,
      7, and 9. mAb T20C specifically recognized the pI 7 form of the enzyme on
      electrophoretic transfer (Western) blots. When analyzed by sodium dodecyl sulfate
      gel electrophoresis under reducing conditions, the eluted pI 7 form was confirmed
      to migrate as a polypeptide of 67 kDa. The 67-kDa pI 7 isoform is a previously
      undescribed form of ACC synthase.

PMID- 16593999
TI  - Two-dimensional protonic percolation on lightly hydrated purple membrane.
AB  - The capacitance and dielectric loss factor were measured for a sample of purple
      membrane of Halobacterium halobium as a function of hydration level (0.017 to
      >0.2 g of water/g of membrane) and frequency (10 kHz to 10 MHz). The capacitance
      and the derived conductivity show explosive growth above a threshold hydration
      level, h(c) approximately 0.0456. The conductivity shows a deuterium isotope
      effect, H/(2)H = 1.38, in close agreement with expectation for a protonic
      process. The level h(c) is frequency independent and shows no deuterium isotope
      effect. These properties are analogous to those found for lysozyme in a related
      study. Protonic conduction for the purple membrane can be considered, as for
      lysozyme, within the framework of a percolation model. The critical exponent, t,
      which describes the conductivity of a percolative system near the threshold, has
      the value 1.23. This number is in close agreement with expectation from theory
      for a two-dimensional percolative process. The dielectric properties of the
      purple membrane are more complex than those of lysozyme, seen in the value of
      h(c) and in the frequency and hydration dependence of the loss factor. There
      appear to be preferred regions of proton conduction. The percolation model is
      based upon stochastic behavior of a system partially populated with conducting
      elements. This model suggests that ion transport in membranes and its control can
      be based on pathways formed of randomly connected conducting elements and that a
      fixed geometry (a proton wire) is not the only possible basis for a mechanism of
      conduction.

PMID- 16594000
TI  - Transformation of the cryobehavior of rye protoplasts by modification of the
      plasma membrane lipid composition.
AB  - The freezing tolerance of protoplasts isolated from nonacclimated rye leaves
      (Secale cereale L. cv Puma) was significantly altered by using a pH-induced
      protoplastliposome fusion technique to modify the lipid composition of the plasma
      membrane. The increase in freezing tolerance was elicited by fusion with
      liposomes composed of either the total phospholipid fraction isolated from the
      plasma membrane of cold-acclimated leaves or single mono- or diunsaturated
      species of phosphatidylcholine (PtdCho). Of the PtdCho species tested,
      dilinoleoylphosphatidylcholine ([Lin(2)]PtdCho) and
      dilinolenoylphosphatidylcholine ([Lnn(2)]PtdCho) liposomes were the most
      effective; 1-palmitoyl-2-oleoylphosphatidylcholine, 1-palmitoyl-2
      linoleoylphosphatidylcholine, or dioleoylphosphatidylcholine liposomes were
      somewhat less effective; dimyristoylphosphatidylcholine or
      dipalmitoylphosphatidylcholine liposomes had no effect. The increased freezing
      tolerance was the result of a transformation in the cryobehavior of the plasma
      membrane during freeze-induced osmotic contraction. In control nonacclimated
      protoplasts, osmotic contraction resulted in endocytotic vesiculation of the
      plasma membrane which was irreversible and resulted in lysis during osmotic
      expansion after melting of the suspending medium. In nonacclimated protoplasts
      fused with mono- or diunsaturated species of PtdCho, osmotic contraction resulted
      in the reversible formation of exocytotic extrusions of the plasma membrane-as
      normally occurs in protoplasts isolated from cold-acclimated leaves (acclimated
      protoplasts). In scanning electron micrographs, the morphology of the extrusions
      of nonacclimated protoplasts fused with [Lin(2)]PtdCho was virtually
      indistinguishable from that of the extrusions formed in acclimated protoplasts.
      These studies provide direct evidence that changes in the lipid composition of
      the plasma membrane are causally related to one facet of the cold-acclimation
      process.

PMID- 16594001
TI  - The dominant non-gibberellin-responding dwarf mutant (D8) of maize accumulates
      native gibberellins.
AB  - The endogenous gibberellins (GAs) were examined from young vegetative shoots of
      the dominant mutant, Dwarf-8, a GA-nonresponder, and normal maize; GA(44),
      GA(17), GA(19), GA(20), GA(29), GA(1), and GA(8), members of the early-13
      hydroxylation pathway, were identified from both kinds of shoots by full-scan
      mass spectra and Kovats retention indices. In addition, we report the
      identification of 3-epi-GA(1), GA(3), GA(4), GA(5), GA(7), GA(9), GA(12), GA(15),
      GA(24), GA(34), and GA(53) by using the same criteria. [1,7,12,18-(14)C(4)]GA(53)
      and -GA(44), [17-(2)H(2)]GA(19), and [17-(13)C,(3)H(2)]GA(20), -GA(29), -GA(1), 
      GA(8), and -GA(5) were used as internal standards to determine the endogenous
      levels of these GAs by measurement of isotope dilution, using capillary gas
      chromatography and selected ion monitoring. Shoots of Dwarf-8 accumulate
      relatively high levels of GA(20), GA(1), and GA(8). The accumulation of GA(1)
      appears to be related to gene dosage. Since Dwarf-8 contains the same pattern of
      GAs as normals (including GA(1) and GA(3)), the genetic control point probably
      lies after GA(1) (and GA(3)). Thus Dwarf-8 may be a GA receptor mutant or a
      mutant that controls a product downstream from the binding of the bioactive GA to
      a receptor.

PMID- 16594002
TI  - Analysis of pivotal-differential evolutionary patterns.
AB  - The numerical analysis of meiosis in hybrids between a wild allotetraploid and an
      autotetraploid of one of its putative diploid progenitors allows the
      identification of which genomes are pairing and also the verification of pivotal
      differential evolution. This type of analysis should be applicable to all genera
      in which allopolyploid series exist.

PMID- 16594003
TI  - Evidence for a single rolling circle in the replication of potato spindle tuber
      viroid.
AB  - We analyzed in vivo-labeled RNA to determine which of the two proposed rolling
      circle models is more likely to depict the replication cycle of potato spindle
      tuber viroid. A key feature distinguishing the two models is the presence of a
      circular monomeric minus strand in one and not the other. Chromatography on
      cellulose CF11 was used to purify a fraction containing the replication
      intermediates free from single-stranded progeny. Heat denaturation followed by
      gel electrophoresis was used to seek possible circular templates-species required
      for rolling-circle replication to take place. Upon heating, a (32)P-labeled RNA
      was released. Limited nuclease digestion ("nicking") revealed that this was a
      unitlength circular RNA. Fingerprinting identified it as a plus strand. No
      circular minus strands were detected in this population or in nuclease-treated
      samples containing RNase T1-resistant cores of the replication complex. Thus,
      potato spindle tuber viroid appears to use an asymmetric pathway in which minus
      strands are synthesized by rolling-circle copying, but plus strands are not. More
      details of the replication pathways used by various viroid-like RNAs are needed
      and will help to establish the evolutionary relationships among these infectious
      agents.

PMID- 16594004
TI  - Vertex representations of quantum affine algebras.
AB  - We construct vertex representations of quantum affine algebras of ADE type, which
      were first introduced in greater generality by Drinfeld and Jimbo. The limiting
      special case of our construction is the untwisted vertex representation of affine
      Lie algebras of Frenkel-Kac and Segal. Our representation is given by means of a
      new type of vertex operator corresponding to the simple roots and satisfying the
      defining relations. In the case of the quantum affine algebra of type A, we
      introduce vertex operators corresponding to all the roots and determine their
      commutation relations. This provides an analogue of a Chevalley basis of the
      affine Lie algebra [unk](n) in the basic representation.

PMID- 16594005
TI  - Hydrogen production and deuterium-proton exchange reactions catalyzed by
      Desulfovibrio nickel(II)-substituted rubredoxins.
AB  - The nickel tetrahedral sulfur-coordinated core formed upon metal replacement of
      the native iron in Desulfovibrio sp. rubredoxins is shown to mimic the reactivity
      pattern of nickel-containing hydrogenases with respect to hydrogen production,
      deuterium-proton exchange, and inhibition by carbon monoxide.

PMID- 16594006
TI  - Monomeric and aggregated bacteriorhodopsin: Single-turnover proton transport
      stoichiometry and photochemistry.
AB  - The question of the basic functional transport unit of bacteriorhodopsin (BR) has
      been addressed by comparing the proton pumping stoichiometry as well as the
      photocycle kinetics of monomeric and aggregated BR in phospholipid vesicles. When
      time-resolved laser spectroscopy was used in combination with the optical pH
      indicator pyranine, single-turnover experiments revealed approximately 0.5-0.8
      and 0.8-1.2 protons vectorially translocated per photocycling monomeric and
      aggregated BR molecule, respectively. Since both these values are akin and very
      similar to the pumping stoichiometry of crystalline BR molecules in the purple
      membrane, the BR monomer has been proven to be the essential transport unit. The
      natural arrangement of the photopigments in a crystalline array of immobilized
      trimers is not required for efficient vectorial proton translocation.

PMID- 16594007
TI  - Cytochrome b-559 and proton conductance in oxygenic photosynthesis.
AB  - Although cytochrome b-559 has long been known as a membrane-bound redox component
      closely linked to the reaction center of the oxygen-generating photosystem
      (PSII), its role in photosynthesis has remained obscure. This paper reports
      evidence and outlines a hypothesis in support of a "b-559 cycle"-i.e., a light
      induced, cytochrome b-559-dependent, cyclic electron transport pathway around
      PSII that promotes translocation of protons from plastoquinol into the aqueous
      domain (lumen) of photosynthetic membranes (thylakoids). Light-induced proton
      transport coupled to light-induced electron transport is an essential aspect of
      energy transduction in photosynthesis because it generates an electrochemical
      proton gradient that drives ATP synthesis by the process of photosynthetic
      phosphorylation. The principal carrier of electrons and protons in thylakoids is
      the plastoquinone/plastoquinol couple. We propose that the b-559 cycle functions
      as a redox-linked proton pump that may operate jointly with the Rieske iron
      sulfur pathway in oxidizing plastoquinol. The overall effect of such concerted
      oxidation of plastoquinol would be the translocation into the thylakoid lumen of
      two protons for each electron transferred from water to plastocyanin via
      plastoquinone.

PMID- 16594008
TI  - Catabolites of chlorophyll in senescing barley leaves are localized in the
      vacuoles of mesophyll cells.
AB  - Senescing barley leaves accumulate a series of pink pigments with the chemical
      properties of catabolites derived from chlorophyll. Levels of the major component
      of this group of pigments were quantified by HPLC and shown to be maximal in
      tissues exhibiting maximal rates of chlorophyll degradation. Protoplasts were
      isolated from senescent leaf tissue and fractionated to yield intact vacuoles and
      plastids. Although small but significant proportions both of total catabolites
      and of the dominant component of the series were recovered from the plastid
      fraction, the vast bulk of these compounds could be assigned to the vacuole.
      These observations suggest a role for the vacuole in the later stages of
      chlorophyll breakdown during senescence.

PMID- 16594009
TI  - Genetic diversity in natural populations of a soil bacterium across a landscape
      gradient.
AB  - Genetic diversity in natural populations of the bacterium Pseudomonas cepacia was
      surveyed in 10 enzymes from 70 clones isolated along a landscape gradient.
      Estimates of genetic diversity, ranging from 0.54 to 0.70, were higher than any
      previously reported values of which we are aware and were positively correlated
      with habitat variability. Patterns of bacterial genetic diversity were correlated
      with habitat variability. Findings indicate that the source of strains used in
      genetic engineering will greatly affect the outcome of planned releases in
      variable environments. Selection of generalist strains may confer a large
      advantage to engineered populations, while selection of laboratory strains may
      result in quick elimination of the engineered strains.

PMID- 16594010
TI  - Spatial patterns in a photobiochemical system.
AB  - Illumination of a system consisting of a vertical tube containing an unstirred
      homogeneous suspension of thylakoids in an imposed linear concentration gradient
      of an electron acceptor, 2,6-dichloroindophenol, gave rise to a one-dimensional
      banded pattern of the acceptor that evolved in a time-dependent manner. The
      spatial pattern was obtained only within certain parameters of the
      dichloroindophenol gradient and with certain concentrations of thylakoids.
      Various numbers of bands were obtained by varying the gradient parameters, the
      thylakoid concentration, or both. Pattern formation was reaction-dependent since
      inhibition of the water-splitting system, either by a physical (heating) or by a
      chemical (methylamine) method, resulted in abolition of the spatial periodicity.
      Obtaining the self-organized redox transition of dichloroindophenol in a gelled
      medium suggests that pattern formation in this system could be explained mainly
      by a reaction-diffusion mechanism.

PMID- 16594011
TI  - Membrane phase transitions are responsible for imbibitional damage in dry pollen.
AB  - We have found that the most probable cause of the leakage seen when dry cells or
      organisms such as seeds, pollen, or yeast cells are plunged into water is a gel
      to liquid crystalline phase transition in membrane phospholipids accompanying
      rehydration. By using Fourier transform infrared spectroscopy we have recorded
      infrared spectra of CH(2) stretching vibrations in dry and partially hydrated
      intact pollen grains of Typha latifolia. The vibrational frequency changes
      abruptly as phospholipids pass through the gel to liquid crystalline phase
      transition. Below the apparent transition, viable pollen shows low germination
      and high leakage when placed in water, but above the transition germination
      increases and leakage decreases. The apparent transition temperature falls with
      increasing water content, much as in pure phospholipids. By using this
      phenomenon, it was possible to construct a hydration-dependent phase diagram for
      the intact pollen. This phase diagram has immediate applications since it has
      high predictive value for the viability of the pollen when it is placed in water.

PMID- 16594012
TI  - Determination of the primary charge separation rate in isolated photosystem II
      reaction centers with 500-fs time resolution.
AB  - We have measured directly the rate of formation of the oxidized chlorophyll a
      electron donor (P680(+)) and the reduced electron acceptor pheophytin a(-)
      (Pheoa(-)) following excitation of isolated spinach photosystem II reaction
      centers at 4 degrees C. The reaction-center complex consists of D(1), D(2), and
      cytochrome b-559 proteins and was prepared by a procedure that stabilizes the
      protein complex. Transient absorption difference spectra were measured from 440
      to 850 nm as a function of time with 500-fs resolution following 610-nm laser
      excitation. The formation of P680(+)-Pheoa(-) is indicated by the appearance of a
      band due to P680(+) at 820 nm and corresponding absorbance changes at 505 and 540
      nm due to formation of Pheoa(-). The appearance of the 820-nm band is
      monoexponential with tau = 3.0 +/- 0.6 ps. The time constant for decay of
      (1*)P680, the lowest excited singlet state of P680, monitored at 650 nm, is tau =
      2.6 +/- 0.6 ps and agrees with that of the appearance of P680(+) within
      experimental error. Treatment of the photosystem II reaction centers with sodium
      dithionite and methyl viologen followed by exposure to laser excitation,
      conditions known to result in accumulation of Pheoa(-), results in formation of a
      transient absorption spectrum due to (1*)P680. We find no evidence for an
      electron acceptor that precedes the formation of Pheoa(-).

PMID- 16594013
TI  - An odyssey of the green sea turtle: Ascension Island revisited.
AB  - Green turtles (Chelonia mydas) that nest on Ascension Island, in the south
      central Atlantic, utilize feeding grounds along the coast of Brazil, more than
      2000 km away. To account for the origins of this remarkable migratory behavior,
      Carr and Coleman [Carr, A. & Coleman, P. J. (1974) Nature (London) 249, 128-130]
      proposed a vicariant biogeographic scenario involving plate tectonics and natal
      homing. Under the Carr-Coleman hypothesis, the ancestors of Ascension Island
      green turtles nested on islands adjacent to South America in the late Cretaceous,
      soon after the opening of the equatorial Atlantic Ocean. Over the last 70 million
      years, these volcanic islands have been displaced from South America by sea-floor
      spreading, at a rate of about 2 cm/year. A population-specific instinct to
      migrate to Ascension Island is thus proposed to have evolved gradually over tens
      of millions of years of genetic isolation. Here we critically test the Carr
      Coleman hypothesis by assaying genetic divergence among several widely separated
      green turtle rookeries. We have found fixed or nearly fixed mitochondrial DNA
      (mtDNA) restriction site differences between some Atlantic rookeries, suggesting
      a severe restriction on contemporary gene flow. Data are consistent with a natal
      homing hypothesis. However, an extremely close similarity in overall mtDNA
      sequences of surveyed Atlantic green turtles from three rookeries is incompatible
      with the Carr-Coleman scenario. The colonization of Ascension Island, or at least
      extensive gene flow into the population, has been evolutionarily recent.

PMID- 16594014
TI  - Young-Capelli symmetrizers in superalgebras.
AB  - Let Super(n)[U [unk] V] be the nth homogeneous subspace of the supersymmetric
      algebra of U [unk] V, where U and V are Z(2)-graded vector spaces over a field K
      of characteristic zero. The actions of the general linear Lie superalgebras pl(U)
      and pl(V) span two finite-dimensional K-subalgebras B and [unk] of
      End(K)(Super(n)[U [unk] V]) that are the centralizers of each other. Young
      Capelli symmetrizers and Young-Capelli *-symmetrizers give rise to K-linear bases
      of B and [unk] containing orthogonal systems of idempotents; thus they yield
      complete decompositions of B and [unk] into minimal left and right ideals,
      respectively.

PMID- 16594015
TI  - Functional evidence for an auxin receptor at the plasmalemma of tobacco mesophyll
      protoplasts.
AB  - Tobacco mesophyll protoplasts were previously shown to respond to
      naphthaleneacetic acid by modifying their transmembrane potential difference. In
      the present work, evacuolated protoplasts were used to show that this response
      resides only at the plasmalemma. This electrical response was investigated by
      using polyclonal antibodies directed against plasma membrane antigens presumably
      involved in the reception and transduction of the auxin signal. An IgG fraction
      from an antiserum directed against the membrane auxin-binding protein from maize
      coleoptile completely inhibited the naphthaleneacetic acid-induced response of
      tobacco protoplasts. The suppression of the auxin-induced variation in the
      transmembrane potential difference by an IgG preparation directed against the
      plasmalemma ATPase from yeast demonstrated the involvement of the ATPase in the
      electrical response. Variation induced by fusicoccin in the transmembrane
      potential difference of tobacco protoplasts was unaffected by the anti-auxin
      binding protein IgG fraction but was completely suppressed by the anti-ATPase IgG
      preparation. These results demonstrate the presence of a membrane receptor for
      auxin at the plasmalemma, the binding of the hormone to this receptor leading to
      the activation of the proton-pumping ATPase. They also show that at least the
      primary steps of activation by naphthaleneacetic acid are distinct from those of
      the fusicoccin-induced response.

PMID- 16594016
TI  - Potential phytotoxicity associated with the use of soil urease inhibitors.
AB  - Recent work in our laboratory showed that the adverse effect of urea fertilizer
      on seed germination and seedling growth in soil is due to ammonia produced
      through hydrolysis of urea by soil urease (NH(2)CONH(2) + H(2)O --> 2NH(3) +
      CO(2)) and can be eliminated by amending the fertilizer with a small amount of a
      urease inhibitor such as N-(n-butyl)thiophosphoric triamide or
      phenylphosphorodiamidate. Continuation of this work showed that these inhibitors
      can induce leaf-tip necrosis in plants. Research to account for this
      phytotoxicity indicated that it resulted from an accumulation of toxic amounts of
      urea in plants through inhibition of urease activity by N-(n-butyl)thiophosphoric
      triamide and phenylphosphorodiamidate. Support for this conclusion was provided
      by experiments showing that these urease inhibitors increased both leaf-tip
      necrosis and urea concentrations in wheat (Triticum aestivum L.) and sorghum
      [Sorghum bicolor(L.) Moench] plants grown in soils treated with urea and that the
      necrotic areas of such plants had a much higher concentration of urea than did
      the nonnecrotic areas. The potential of urease inhibitors for inducing
      phytotoxicity should not preclude their use to eliminate the adverse effects of
      urea fertilizers on seed germination and seedling growth in soil because the
      ammonia produced through hydrolysis of urea fertilizer by urease is much more
      detrimental to plant growth than is the urea accumulation induced by urease
      inhibitors.

PMID- 16594017
TI  - Early nodulin genes are induced in alfalfa root outgrowths elicited by auxin
      transport inhibitors.
AB  - Rhizobium nod genes are essential for root hair deformation and cortical cell
      division, early stages in the development of nitrogen-fixing root nodules. Nod(-)
      mutants are unable to initiate nodules on legume roots. We observed that N-(1
      naphthyl)phthalamic acid and 2,3,5-triiodobenzoic acid, compounds known to
      function as auxin transport inhibitors, induced nodule-like structures on alfalfa
      roots. The nodule-like structures (pseudonodules) were white, devoid of bacteria,
      and resembled nodules elicited by Rhizobium meliloti exopolysaccharide (exo)
      mutants at both the histological and molecular level. Two nodulin genes, ENOD2
      and Nms-30, were expressed. RNA isolated from the nodule-like structures
      hybridized to pGmENOD2, a soybean early nodulin cDNA clone. RNA isolated from
      roots did not hybridize. We determined by in vitro translations of total RNA that
      the alfalfa nodulin transcript Nms-30 was also expressed in the nodule-like
      structures. The late expressed nodulin genes, such as the leghemoglobin genes,
      were not transcribed. Because N-(1-naphthyl)phthalamic acid and 2,3,5
      triiodobenzoic acid induce the development of nodules on alfalfa roots, we
      suggest that the auxin transport inhibitors mimic the activity of compound(s)
      made upon the induction of the Rhizobium nod genes.

PMID- 16594018
TI  - Regulation of pheromone biosynthesis by a brain hormone in two moth species.
AB  - Experiments were performed to characterize the action of a brain hormone on
      pheromone biosynthesis in female redbanded leafroller and cabbage looper moths.
      Results showed that the two species differed in their respective control
      mechanisms. In the cabbage looper, pheromone titer from decapitated females that
      received either saline or brain extract injections was not significantly
      different from control females, suggesting that pheromone biosynthesis was not
      dependent on the presence of the brain hormone. In contrast, with redbanded
      leafroller females, studies using radiolabeled acetate incorporation as well as
      incorporation of deuterium-labeled hexadecanoic acid showed that (i) the brain
      hormone was required for pheromone biosynthesis, (ii) the brain hormone regulated
      pheromone biosynthesis by activating synthesis of octadecanoyl and hexadecanoyl
      intermediates, and (iii) the brain hormone did not control other enzymes in the
      pathway. Regulation of fatty acid synthetase was unlikely since assays of the
      enzyme from decapitated and normal females showed no differences in the amount or
      distribution of the 18- and 16-carbon acyl end products. These results in
      conjunction with those from organ cultures of the pheromone gland suggest that
      the brain hormone acts by increasing the substrate supply for fatty acid
      synthesis.

PMID- 16594019
TI  - Rate of evolution of a character without epistasis.
AB  - IT IS SHOWN THAT THE RATE OF CHANGE OF THE MEAN OF A CHARACTER UNDER SELECTION IS
      [FORMULA: see text] where C, W, DeltaZ, and B denote the genic (additive genetic)
      covariance of the character and fitness (i.e., the covariance of the average
      effect on the character and the average excess for fitness of every allele that
      affects the character), the mean fitness, the average of the changes in the
      genotypic values of the character over the next generation, and a correction
      term, respectively. Generations are discrete and nonoverlapping; the monoecious
      population mates at random. The character is determined by arbitrarily many
      multiallelic loci without epistasis; the linkage map is also arbitrary. If there
      is no dominance, then B = 0; if, in addition, the genotypic values of the
      character are constant, then Delta Z = C/ W. Even if dominance is present, for
      weak selection and slowly varying genotypic values, Delta Z approximately C/ W.
      If the character is fitness itself, then C is the genic variance in fitness.

PMID- 16594020
TI  - Regulation of heat production in the inflorescences of an Arum lily by endogenous
      salicylic acid.
AB  - We have recently purified calorigen, the natural trigger for heat production in
      the inflorescences of Sauromatum guttatum Schott (voodoo lily), a thermogenic
      plant, and identified it as salicylic acid. Since then an analytical assay was
      developed that allows the quantitation of salicylic acid in plant tissues. This
      assay was used to demonstrate that on the day preceding the day of blooming the
      levels of salicylic acid in the thermogenic organs (appendix and lower spadix) of
      the voodoo lily increased almost 100-fold, reaching a level of 1 mug/g of fresh
      weight. The level of salicylic acid in the appendix started to rise in the
      afternoon and reached its maximum in the late evening, whereas the maximum
      accumulation of salicylic acid in the lower spadix occurred late at night. The
      increase in salicylic acid level in the appendix was followed the next morning by
      a spectacular metabolic burst that lasted for about 7 hr and at its peak
      increased the appendix temperature by over 12 degrees C. The second, 14-hr-long,
      thermogenic episode in the lower spadix started late at night and ended on the
      following morning, after maximum temperature increases of more than 10 degrees C.
      The concentration of salicylic acid in both thermogenic tissues promptly returned
      to basal, preblooming levels at the end of the thermogenic periods. The
      thermogenic response was under strong photoperiodic and developmental control,
      with salicylic acid eliciting much stronger thermogenic responses in light than
      in darkness. Similar surges in salicylic acid occurred in nonthermogenic male and
      female flowers, while the concentration of salicylic acid in the spathe remained
      consistently below 20 ng/g of fresh weight. Of 33 analogs of salicylic acid
      tested, only 2,6-dihydroxybenzoic acid and acetylsalicylic acid (aspirin) were
      thermogenic. The activity of 2,6-dihydroxybenzoic acid exceeded that of salicylic
      acid.

PMID- 16594021
TI  - On the evolutionary origin of the plant mitochondrion and its genome.
AB  - Higher plants occupy very different positions in the mitochondrial and nuclear
      lineages of global phylogenetic trees based on conserved regions of small subunit
      (SSU) and large subunit (LSU) rRNA sequences. In the nuclear subtree, plants
      branch off late, at a position reflecting a massive radiation of the major
      multicellular (and some unicellular) groups; in the mitochondrial subtree, in
      contrast, plants branch off early, near the point of connection between the
      mitochondrial and eubacterial lineages. Moreover, in the nuclear lineage, plants
      branch together with the unicellular green alga Chlamydomonas reinhardtii,
      whereas in the mitochondrial lineage (in both SSU and LSU trees), metaphytes and
      chlorophyte branch separately. Statistical evaluation indicates that the
      anomalous branching position of higher plants in the mitochondrial lineage is not
      a treeing artifact attributable to the relatively rapid rate of sequence
      divergence of non-plant mitochondrial rRNA sequences. In considering alternative
      biological explanations for these results, we are led to propose that the rRNA
      genes in plant mitochondria may be of more recent evolutionary origin than the
      rRNA genes in other mitochondria. This proposal has implications for monophyletic
      vs. polyphyletic scenarios of mitochondrial origin and is consistent with other
      evidence indicating that plant mtDNA is an evolutionary mosaic.

PMID- 16594022
TI  - Bilaterians of the Precambrian-Cambrian transition and the annelid-arthropod
      relationship.
AB  - The Late Proterozoic fossil record contains the remains of animals that may
      represent a grade of organization not found among living metazoans. These forms
      were segmented and large enough to require a hemocoel, yet evidently were not
      capable of forming penetrating burrows, which are essentially absent from
      contemporaneous sediments containing locally common but chiefly horizontal trace
      fossils. As has been noted, there is no evidence that Late Proterozoic
      invertebrates possessed a coelom suited for peristaltic burrowing. Therefore, the
      annelidan body plan had probably not appeared. It is not implausible, however,
      that coelomic spaces in the form of ducts or organ sacs were present in Late
      Proterozoic segmented forms. Uniramians, some of which employ the hemocoel
      hydrostatically in lobopodal locomotion, may be allied to segmented hemocoelic
      forms not unlike sprigginids. Coelomic spaces may have been exploited in some
      protoarthropod lineages to enhance pedal-wave locomotion, but probably there are
      no eucoelomic forms in arthropodan ancestry. Annelids may represent an early
      divergent branch of seriated worms, perhaps rather nemertine-like at first, that
      developed eucoelomic compartments only in Cambrian time. The extinct grade is
      most likely to have arisen from flatworm-like ancestors. Of all the proposed
      phylogenies examined, only that of Manton closely anticipates these
      interpretations of the early metazoan fossil record.

PMID- 16594023
TI  - Neural regulation of sex pheromone biosynthesis in Heliothis moths.
AB  - Pheromone biosynthesis in females of Heliothis zea is regulated endogenously by a
      neuropeptide produced in the subesophageal ganglion. We have found that the
      ventral nerve cord must be intact for normal induction of pheromone biosynthesis
      and that pheromonotropic activity is associated with extracts of the abdominal
      nerve cord, but only during the period when pheromone is produced. We did not
      find evidence of pheromonotropic activity in hemolymph obtained from females that
      were producing pheromone. Extracts of the brain-subesophageal ganglion complex,
      which contain pheromone biosynthesis activating neuropeptide (PBAN), induced
      pheromone biosynthesis when applied to the terminal abdominal ganglion only if
      nerves from this ganglion to the pheromone gland were intact. Brain-subesophageal
      ganglion extracts did not induce biosynthesis when applied directly to the
      pheromone glands in vitro. From our results, we conclude that the target site of
      PBAN is not the pheromone gland but the terminal abdominal ganglion, and we
      hypothesize that the abdominal nerve cord transports PBAN to the terminal
      abdominal ganglion.

PMID- 16594024
TI  - Standard basis in supersymplectic algebras.
AB  - An integral standard basis is given for products of Pfaffians containing
      positively and negatively signed variables. Applications to invariant theory are
      derived.

PMID- 16594025
TI  - Characterization of vacuolar and extracellular beta(1,3)-glucanases of tobacco:
      Evidence for a strictly compartmentalized plant defense system.
AB  - beta(1,3)-Glucanases are a class of hormonally and developmentally regulated
      plant hydrolytic enzymes, which are also induced upon pathogen infection,
      suggesting a role of these hydrolases in the defense response to pathogens. We
      have purified several beta(1,3)-glucanases present in tobacco leaves from control
      plants and from plants treated with salicylic acid or infected with Pseudomonas
      syringae and studied in detail the subcellular localization of the different
      isoforms. Partial protein sequence analysis demonstrated that each of the
      different isoforms had a unique amino acid sequence and was therefore encoded by
      a different gene. We have also demonstrated that two of these isoforms, similar
      to the cytokinin/auxin-regulated isoforms previously isolated from tobacco cell
      suspensions, are located in the central vacuole. Upon salicylic acid treatment or
      P. syringae infection, three secreted isoforms are induced, belonging to the so
      called pathogenesis-related proteins. These pathogenesis-related beta(1,3)
      glucanases are all distinct from each other and also different from the vacuolar
      isoforms. We demonstrate that the vacuolar isoforms are not secreted to the
      extracellular spaces of the plant following pathogen infection, suggesting that
      any function they play in the plant defense response is restricted to an
      intracellularly coordinated defense process.

PMID- 16594026
TI  - Nitrogen-dependent regulation of photosynthetic gene expression.
AB  - Nitrogen-limited Chlamydomonas reinhardtii is chlorotic and very deficient in
      chlorophyll a/b light-harvesting complexes (LHC). Rates of synthesis of
      photosynthetic proteins, but especially the LHC apoproteins, are reduced 10- to
      40-fold. Moderately high levels of chloroplast transcripts accumulate in nitrogen
      limited cells, and there is a correlation between chloroplast DNA levels and
      chloroplast mRNA abundance. In contrast, nuclear transcripts encoding LHCII and
      ribulose 1,5-bisphosphate carboxylase small subunits are markedly reduced. Thus,
      nitrogen availability affects chloroplast protein synthesis by inhibition of
      translation and, to a lesser extent, chloroplast DNA amplification. Regulation of
      nuclear-encoded photosynthetic proteins by nitrogen is achieved through
      mechanisms affecting transcription and/or mRNA stability.

PMID- 16594027
TI  - Ammonia and thermotaxis: Further evidence for a central role of ammonia in the
      directed cell mass movements of Dictyostelium discoideum.
AB  - Evidence is presented to support the hypothesis that, in addition to its possible
      role in mediating chemo- and phototaxis, ammonia (NH(3)) is also the key
      substance responsible for directing thermotaxis of the migrating slugs of
      Dictyostelium discoideum. NH(3) is produced by the cells of the slug and we show
      that high and low concentrations of NH(3) decrease the speed of the amoebae while
      intermediate concentrations increase their speed. NH(3) production by amoebae is
      affected by temperature: the greater the temperature, the more NH(3) is produced.
      From these facts we speculate that both the positive and the negative thermotaxis
      found in slugs can be explained by temperature gradients stimulating regional
      differences in NH(3) production, and depending upon the temperature, the amount
      of NH(3) will either be in the range that stimulates or inhibits the rate of
      movement. If this explanation is correct, then minute localized differences in
      the production of NH(3) and their differential effect on cell speed could account
      for all the directed movements of the cell masses of these slime molds.

PMID- 16594028
TI  - Gene-controlled cytosine demethylation in the promoter region of the Ac
      transposable element in maize.
AB  - The transposase product of the Ac transposable element causes demethylation of
      the BamHI site in the promoter region of Ac. This site remains methylated in Ds9,
      the deletional derivative of Ac that fails to make an active transposase. In the
      presence of an active Ac element the BamHI site of Ds9 is demethylated.
      Transcription of the element is correlated with the demethylation of the promoter
      region. Evidence is presented that supports the model that the trans-acting
      protein causes site-specific demethylation by inducing a configuration change in
      chromatin structure making the site inaccessible to the methylase. A chromosome
      alteration that involves the insertion of the 4.5-kilobase Ac element results in
      the methylation of Pvu I target sites about 1 kilobase removed from the point of
      insertion.

PMID- 16594029
TI  - Isolation and identification of a diuretic hormone from the tobacco hornworm,
      Manduca sexta.
AB  - A diuretic hormone (DH) has been isolated from pharate adult heads of Manduca
      sexta by a nine-step purification procedure. The primary structure of the amino
      terminal 40 residues was determined by sequence analysis of intact DH. The
      structure of an amidated carboxyl-terminal tryptic hexapeptide was characterized
      by sequence analysis of the peptide, and this hexapeptide was later compared by
      reversed-phase liquid chromatography with two synthetic hexapeptides with the
      free acid or amide at the carboxyl terminus. The complete structure of M. sexta
      DH was established as a 41-residue peptide without disulfide bonds: H-Arg-Met-Pro
      Ser-Leu-Ser-Ile-Asp-Leu-Pro-Met-Ser-Val-Leu-Arg-Gln-Lys-Leu-Ser -Leu-Glu-Lys-Glu
      Arg-Lys-Val-His-Ala-Leu-Arg-Ala-Ala-Ala-Asn-Arg-Asn-Phe-Leu- Asn-Asp-Ile-NH(2).
      M. sexta DH was synthesized and shown to have chromatographic and biological
      properties identical with those of the native material. Synthetic DH stimulated
      fluid excretion in vivo upon injection into larval M. sexta and newly emerged
      adult Pieris rapae. M. sexta DH has considerable sequence homology with
      corticotropin-releasing factor, urotensin I, and sauvagine.

PMID- 16594030
TI  - Two motion perception mechanisms revealed through distance-driven reversal of
      apparent motion.
AB  - We demonstrate two kinds of visual stimuli that exhibit motion in one direction
      when viewed from near and in the opposite direction from afar. These striking
      reversals occur because each kind of stimulus is constructed to simultaneously
      activate two different mechanisms: a short-range mechanism that computes motion
      from space-time correspondences in stimulus luminance and a long-range mechanism
      in which motion computations are performed, instead, on stimulus contrast that
      has been full-wave rectified (e.g., on the absolute value of contrast).

PMID- 16594031
TI  - Biregular classification of Fano 3-folds and Fano manifolds of coindex 3.
AB  - The Fano 3-folds and their higher dimensional analogues are classified over an
      arbitrary field k [unk] C by applying the theory of vector bundles (in the case
      B(2) = 1) and the theory of extremal rays (in the case B(2) >/= 2). An n
      dimensional smooth projective variety X over k is a Fano manifold if its first
      Chern class c(1)(X) epsilon H(2)(X, Z) is positive in the sense of Kodaira
      [Kodaira, K. (1954) Ann. Math. 60, 28-48] (or ample). If n = 3 and c(1)(X)
      generates H(2)(X, Z), then either (i) X is a complete intersection in a Grassmann
      variety G with respect to a homogeneous vector bundle E on G: the rank of E is
      equal to codim(G)X and X is isomorphic to the zero locus of a global section of
      E, (ii) X is a linear section of a 10-dimensional spinor variety X(12) (10) [unk]
      P(k) (15), or (iii) X is isomorphic to a double cover of P(k) (3), a 3
      dimensional quadric Q(k) (3), or a quintic del Pezzo 3-fold V(5) [unk] P(k) (6).
      If n = 4 and c(1)(X) is divisible by 2, then X [unk] C is isomorphic to (a) a
      complete intersection in a homogeneous space or its double cover, (b) a product
      of P(1) and a Fano 3-fold, (c) the blow-up of Q(4) [unk] P(5) along a line or
      along a conic, or (d) a P(1)-bundle compactifying a line bundle on P(3) or on
      Q(3) [unk] P(4).

PMID- 16594032
TI  - Single-strand-preferring nuclease activity in wheat leaves is increased in
      senescence and is negatively photoregulated.
AB  - Single-strand-preferring nucleases (EC 3.1.30.1) selectively cleave
      internucleotide bonds in single-stranded regions of predominantly duplex DNA and
      DNA.RNA hybrids and extensively degrade denatured DNA and RNA. The functions of
      single-strand-preferring nuclease in plants are unknown. We have monitored this
      nuclease activity in flag leaves of wheat (Triticum aestivum L. cv. Chinese
      Spring) undergoing natural senescence and in primary leaves of wheat seedlings
      undergoing dark-induced senescence. In falg leaves, nuclease activity remained at
      basal levels during the first 2 weeks after anthesis, while chlorophyll content
      increased to a maximum. Nuclease activity then rose in concert with a decline in
      chlorophyll, reaching a 16-fold elevation at 5 weeks post-anthesis, when 53% of
      the chlorophyll had been lost. When 8-day-old wheat seedlings were induced to
      senesce by placing them in darkness, nuclease activity rose without apparent lag,
      reaching a 13-fold elevation in 7 days, when 61% of the chlorophyll had been
      lost. The increase in nuclease activity was reversible upon reexposure of
      seedlings to light, a decline beginning without apparent lag. Reversibility was
      complete for plants that had been held in darkness for 5 days, with activity
      returning to the control level in 2 days. These senescence-related changes in
      nuclease activity, measured in conventional assays, were consistent with
      concomitant analysis by activity staining of sodium dodecyl
      sulfate/polyacrylamide gels. We conclude that an increase in single-strand
      preferring nuclease activity is closely associated with wheat leaf senescence and
      that nuclease activity is subject to negative photoregulation.

PMID- 16594033
TI  - Dual promoter of Agrobacterium tumefaciens mannopine synthase genes is regulated
      by plant growth hormones.
AB  - Temporal and spacial distribution of mannopine synthase (mas) promoter activity
      was determined throughout the development of transgenic tobacco plants using
      bacterial luciferase luxA and luxB as reporter genes. Luciferase activity was
      determined by luminometry in vitro and visualized by computer-enhanced single
      photon video imaging in vivo. The activity of the mas dual promoters increased
      basipetally in developing plants and was wound-inducible in leaf and stem tissue.
      Hormone bioassays with isolated plant tissues and tumors deficient in the
      transferred DNA (T-DNA)-encoded genes iaaM, iaaH, and ipt indicated that activity
      of the mas dual promoters is regulated by auxin and enhanced by cytokinin in both
      differentiated and tumorous plant cells.

PMID- 16594034
TI  - The evolution of eusociality: Reproductive head starts of workers.
AB  - In eusocial species, many individuals forego their personal reproduction to aid
      the reproduction of their mother or other relatives. Kin selection can favor such
      behavior for any positive degree of relatedness to the individuals being helped,
      provided the helper gives them a sufficiently large fitness gain compared to the
      fitness cost of giving up its own reproduction. Yet, little attention has been
      given to the question of how helpers can aid relatives more than they can aid
      themselves, particularly in species lacking morphologically specialized castes.
      One answer to this question is explored here. When a potential helper is born
      into a colony that has immature young, its help may quickly bring those young to
      the age of independence. If it left to reproduce alone, it would have to bring
      its own offspring all the way to independence. The consequences of early
      mortality therefore differ: solitary reproducers that die early will fail to
      bring any young to independence, while helpers that die at the same age may have
      made substantial contributions. Published data from four polistine wasps show
      that high adult mortality rates and long periods of offspring dependence combine
      to provide a large selective advantage for worker behavior.

PMID- 16594035
TI  - Wheat tetrameric inhibitors of insect alpha-amylases: Alloploid heterosis at the
      molecular level.
AB  - Tetrameric inhibitors of heterologous alpha-amylases have been characterized in
      allohexaploid wheat, Triticum aestivum (genomes AABBDD), as well as in Triticum
      turgidum (AABB) and Triticum tauschii (DD). Their subunits have been identified
      as the previously described CM proteins. Single oligomeric species were observed
      in T. Turgidum (subunits CM2, CM3A, and CM16) and in T. tauschii (CM1, CM3D, and
      CM17) by a two-dimensional electrophoretic method that does not dissociate the
      inhibitors in the first dimension. Multiple tetrameric species, resulting from
      different combinations of the subunits contributed by the two ancestral species,
      are observed by the same procedure in T. aestivum. The three types of subunits
      were required for significant activity when the inhibitor of T. turgidum was
      reconstituted from the purified subunits, whereas, in the case of T. tauschii,
      binary mixtures involving subunit CM1 also had some activity. Additional
      combinations of the subunits present in these two species, which occur in the
      allohexaploid T. aestivum, were also reconstituted, and their inhibitory
      activities ranged from 144% to 33% the activity of the reconstituted inhibitor
      from T. tauschii. The activity of these inhibitors toward the alpha-amylase (1,4
      alpha-D-glucan glucanohydrolase, EC 3.2.1.1) of the insect Tenebrio molitor is
      much greater than that against the salivary enzyme. These observations, together
      with the previously established chromosomal locations of genes encoding CM
      proteins, fit a model of alloploid heterosis at the molecular level.

PMID- 16594036
TI  - Differences in fatty acid composition between vegetative cells and N(2)-fixing
      vesicles of Frankia sp. strain CpI1.
AB  - When growing on N(2), actinomycetes from the genus Frankia form multicellular
      structures that contain nitrogenase. The structures are referred to as vesicles
      and are indistinguishable from vesicles formed when Frankia sp. are in root
      nodule symbioses. Vesicles isolated from N(2)-grown cells of Frankia sp. strain
      CpI1 had a significantly higher amount and different composition of fatty acids
      than did vegetative cells recovered from NH(4) (+)-containing medium. Lipids from
      vesicles, whole cells grown on N(2), and whole cells grown on NH(4) (+) were
      fractionated by silicic acid chromatography into neutral lipids, glycolipids, and
      polar lipids. The fatty acids were transesterified by methanolysis and analyzed
      by gas chromatography and mass spectrometry. Vesicles had considerably higher
      amounts of fatty acids in the neutral and glycolipid fractions but lower amounts
      of polar lipid fatty acids than did vegetative cells. Polar lipids from vesicles
      had a higher proportion of mono-unsaturated and cyclopropane fatty acids and a
      lower proportion of isobranched fatty acids than did polar lipids from NH(4) (+)
      grown or N(2)-grown cells. The neutral lipid and glycolipid fractions contained
      several long-chain compounds with molecular ions at m/z 408 and 410. The
      proportions of these compounds were significantly higher in the lipids from
      vesicles than from vegetative cells. These results suggest that lipids in
      vesicles might be involved in the protection of nitrogenase from O(2) and suggest
      a parallel with the glycolipids involved in protecting nitrogenase from O(2) in
      the cyanobacterial heterocysts.

PMID- 16594037
TI  - Persistence of nonoptimal strategies.
AB  - Metastable configurations in open computational systems with local minima in
      their optimality functions are shown to be very long lived, which makes them
      effectively stable. When rare transitions to the global optimum do occur, they
      happen extremely fast, in analogy to models of punctuated evolution in biology.
      These results are obtained by introducing a thermodynamic-like formalism that
      allows for a simple analysis of nonlinear game dynamics in computational
      ecosystems.

PMID- 16594038
TI  - Superconducting properties of copper oxide high-temperature superconductors.
AB  - The equations for the magnon pairing theory of high-temperature copper-oxide
      based superconductors are solved and used to calculate several properties,
      leading to results for specific heat and critical magnetic fields consistent with
      experimental results. In addition, the theory suggests an explanation of why
      there are two sets of transition temperatures (T(c) approximately 90 K and T(c)
      approximately 55 K) for the Y(1)Ba(2)Cu(3)O(6+x) class of superconductors. It
      also provides an explanation of why La(2-x)Sr(x)CuO(4) is a superconductor for
      only a small range of x (and suggests an experiment to independently test the
      theory). These results provide support for the magnon pairing theory of high
      temperature superconductors. On the basis of the theory, some suggestions are
      made for improving these materials.

PMID- 16594039
TI  - Theory of hexagonal and stripe phases in monolayers.
AB  - Epifluorescence microscopy can be used to visualize the shapes of solid lipid
      domains in two-phase regions of monolayers at the air-water interface. The shapes
      of certain lipid domains result from a competition between a one-dimensional line
      tension and long-range intermolecular electrostatic repulsion. Under specified
      conditions, a finite two-dimensional domain with one shape can undergo a sharp
      transition to a second shape, as the area of the domain is changed. Two
      dimensional infinite arrays of domains can also have transitions involving
      changes in the shapes and patterns of domains, such as the stripe to hexagonal
      phase transition [Andelman, D., Brochard, F. & Joanny, J. F. (1987) J. Chem.
      Phys. 86, 3673-3681]. The present paper treats the hexagonal and stripe phases
      with the same approximations and methods of calculation as used previously for
      the isolated, finite domains. It is shown that one effect of electrostatic
      repulsion between domains is to cause these domains to increase in size as they
      approach one another on monolayer compression. It is also shown that there can be
      two distinct conditions where the hexagonal and stripe phases coexist.

PMID- 16594040
TI  - Comparison of seismic and hydrodynamic yield determinations for the Soviet joint
      verification experiment of 1988.
AB  - Seismic magnitudes determined from surface and body waves for the Soviet
      underground nuclear explosion of September 14, 1988, are used to calculate the
      yield of that event from previously derived calibration curves. The yield
      obtained by combining the two seismic estimates is 113 kilotons, which is very
      close to those obtained by hydrodynamic measurements made on-site. This
      comparison substantiates previous conclusions about the sizes of past Soviet
      weapons tests and compliance with the Threshold Test Ban Treaty. The factor of
      uncertainty in the combined seismic yield is 1.28 at the 68% and 1.62 at the 95%
      confidence levels, demonstrating that accuracies considerably better than a
      factor of 2 can be obtained by combining seismic determinations of yield.

PMID- 16594041
TI  - Compact negatively curved manifolds (of dim [unk] 3,4) are topologically rigid.
AB  - Let M be a complete (connected) Riemannian manifold having finite volume and
      whose sectional curvatures lie in the interval [c(1), c(2)] with -infinity <
      c(1)[unk]c(2) < 0. Then any proper homotopy equivalence h:N --> M from a
      topological manifold N is properly homotopic to a homeomorphism, provided the
      dimension of M is >5. In particular, if M and N are both compact (connected)
      negatively curved Riemannian manifolds with isomorphic fundamental groups, then M
      and N are homeomorphic provided dim M [unk] 3 and 4. {If both are locally
      symmetric, this is a consequence of Mostow's rigidity theorem [Mostow, G. D.
      (1967) Publ. Inst. Haut. Etud. Sci. 34, 53-104].} When M has infinite volume we
      can still calculate the surgery L-groups of pi(1)M, even when dim M = 3, 4, or 5,
      provided M is locally symmetric. An identification of the weak homotopy type of
      the homeomorphism group of (finite volume) M is also made through a stable range.
      We have previously announced these results for the special case that c(1) = c(2)
      = -1.

PMID- 16594042
TI  - An upper bound for the number of electrons in a large ion.
AB  - Let E(Z, N) be the ground-state energy of N quantized electrons and a single
      nucleus of charge Z. For fixed Z, E(Z, N) is independent of N for N >/=
      N(critical)(Z). Physically, this means that at most N(critical) electrons can
      bind to the nucleus. We prove that N(critical) </= Z + CZ(a) with a = 0.84.

PMID- 16594043
TI  - Affinity labeling of Avena phytochrome with ATP analogs.
AB  - The presence of ATP-dependent, polycation-stimulated protein kinase activity in
      highly purified phytochrome preparations [Wong, Y.-S., Cheng, H.-C., Walsh, D. A.
      & Lagarias, J. C. (1986) J. Biol. Chem. 261, 12089-12097] has renewed the
      hypothesis that the phytochrome photoreceptor possesses enzymatic activity. A
      prerequisite for protein kinase function is the presence of an ATP binding site.
      Here we present evidence for a nucleoside triphosphate binding site(s) in the
      phytochrome molecule. Two ATP analogs, 5'-p-fluorosulfonylbenzoyladenosine and 8
      azidoadenosine 5'-triphosphate, were used to affinity label purified Avena
      phytochrome. Labeling with both reagents is stimulated by the polycations
      poly(Lys(75),Ala(25)) and histone H1. Coincubation with ATP inhibits the
      polycation-stimulated labeling of phytochrome. In similar experiments GTP, CTP,
      UTP, ADP, and pyrophosphate, but not adenosine or AMP, also prevent photoaffinity
      labeling of phytochrome.

PMID- 16594044
TI  - Heat shock protein hsp70 cognate gene expression in vegetative and reproductive
      organs of Lycopersicon esculentum.
AB  - We have detected hsc70 gene expression (heat shock protein hsp70 cognate) during
      vegetative growth and reproductive development in tomato (Lycopersicon
      esculentum). Using RNA from a tomato hsc70 cDNA as a probe in in situ
      hybridizations, we have determined expression patterns of hsc70 in nonstressed
      tomato roots, stems, leaves, flowers, and developing fruits. We have localized
      high levels of hsc70 transcript to the vascular system of the ovary, dividing
      cells of the lateral root tips, and the inner integument of developing seeds. We
      also see expression in the transmitting tissue, in immature anthers, and in
      embryos. We cannot detect expression in mature pollen, xylem, or ovules. These
      data indicate that the expression of at least some tomato hsp70 family members is
      developmentally regulated.

PMID- 16594045
TI  - A generalization of the Kostant-Macdonald identity.
AB  - Let X be a smooth projective variety admitting an algebraic vector field V with
      exactly one zero and a holomorphic C(*)-action lambda so that the condition
      dlambda(t).V = t(p)V holds for all t in C(*). The purpose of this note is to
      report on a product formula for the Poincare polynomial of X which specializes to
      the classical identity [Formula: see text] when X is the flag variety of a
      semisimple complex Lie group. A surprising corollary is that the second Betti
      number of such an X is the multiplicity of largest weight of the linear C(*)
      action on the tangent space of X at the sink of lambda. We discuss several
      examples, including a construction of the rational Fano 3-folds A'(22) and B(5)
      which is due to Konarski [Konarski, J. (1989) in C.M.S. Conference Proceedings,
      ed. Russell, P. (Am. Math. Soc., Providence, RI), in press].

PMID- 16594046
TI  - The 6S(0)-6P(0) transition in thallium isotope ion Tl: A superior atomic clock.
AB  - Experimental and theoretical studies of the forbidden J = 0 --> J' = 0 optical
      transition 6(1)S(0)-6(3)P(0) in the odd Hg isotopes are in the literature. From
      this work natural width and quadratic Zeeman effect have been estimated for the
      same line in the isoelectronic, even thallium ion (204)Tl(+), which has a very
      small nuclear magnetic moment. For the m(F) = 0 --> 0 component a linewidth of
      <0.01 Hz and a quadratic Zeeman shift <10(-18) at 0.1 Gauss are found, compared
      to 1 Hz and approximately 10(-8) for the hydrogen maser. Electronic quadrupole
      moments vanish for both J and J' states and with them shifts due to electric
      field gradients. All shifts are orders of magnitude smaller than for Hg(+) and
      Ba(+), which have been studied as atomic clock elements.

PMID- 16594047
TI  - Activation of the T-DNA transfer process in Agrobacterium results in the
      generation of a T-strand-protein complex: Tight association of VirD2 with the 5'
      ends of T-strands.
AB  - The T-DNA transfer process of Agrobacterium is activated following induction of
      expression of the Ti plasmid virulence (vir) genes. The virD1 and virD2 gene
      products are required for the production of nicks at the T-DNA borders and for
      the generation of free linear single-stranded copies of the T-DNA region, T
      strands. T-strands are complexed with proteins in vir-induced bacteria, since T
      strands partition to the aqueous/phenol interface in non-Pronasetreated total
      cell extracts. To determine whether the proteins are tightly associated with T
      strands, DNA-protein complexes were purified away from bulk proteins by
      adsorption to glass beads. A 58-kDa protein was specifically released from vir
      induced DNA-protein complexes after treatment with S1 nuclease to digest single
      stranded DNA. The 58-kDa protein was identified as VirD2 by using VirD2-specific
      antibodies. The tight association of VirD2 with T-strands was shown directly by
      using VirD2-specific antibody to isolate T-strands. The 5' side of the border
      nick sites on the Ti plasmid was also shown to be tightly associated with
      protein. The data suggest that after VirD1/VirD2-dependent nicking at the T-DNA
      borders, the VirD2 protein remains bound to the 5' end of the nick, and the VirD2
      protein continues to bind tightly to this 5' end during unwinding (or
      displacement) of the T-strand from the Ti plasmid T-DNA region. The tight binding
      of VirD2 to T-strands suggests that this protein has additional functions in T
      strand generation and potentially in the later steps of T-DNA transfer.

PMID- 16594048
TI  - Translational coupling of the maize chloroplast atpB and atpE genes.
AB  - The genes for the beta and epsilon subunits of maize chloroplast ATP synthase are
      encoded by the organelle genome, are cotranscribed, and have overlapping
      translation initiation and termination codons. To determine whether the atpB and
      atpE genes are translationally coupled, they were transformed into Escherichia
      coli on a multicopy plasmid. Synthesis of full-length beta and epsilon
      polypeptides demonstrated correct initiation of translation by the bacterial
      ribosomes. To assay for translational coupling, the promoter-distal atpE gene was
      fused to lacZ, resulting in the synthesis of an active hybrid beta-galactosidase.
      A frameshift mutation was introduced into the promoter-proximal atpB gene, and
      its effect on the transcription and translation of the atpE::lacZ fusion was
      measured. The mutation resulted in a 1000- to 2000-fold reduction in beta
      galactosidase activity, but only a 2-fold decrease in LacZ mRNA synthesis rates
      or galactoside transacetylase levels. Similar results were obtained when the
      atpB/atpE::lacZ fusion and the atpB frameshift mutation were introduced into the
      photosynthetic cyanobacterium Synechocystis sp. PCC6803. We show that >99% of
      atpE translation depends on successful translation of atpB and, thus, conclude
      that the two genes are translationally coupled.

PMID- 16594049
TI  - Specific binding of victorin to a 100-kDa protein from oats.
AB  - Susceptibility of oats to victoria blight, caused by the fungus Cochliobolus
      victoriae, and sensitivity to the host-specific toxin victorin, produced by the
      fungus, are controlled by the dominant allele at the Vb locus. It has been
      postulated that the Vb locus encodes a toxin receptor, although direct evidence
      for such a receptor is not available. Our recent studies on structure-activity
      relationships of the toxin established a methodology for producing (125)I-labeled
      victorin. Electrophoretic analysis of proteins from isogenic susceptible and
      resistant oat genotypes following treatment of leaves with radiolabeled victorin
      showed that victorin binds in a covalent and a genotype-specific manner to a 100
      kDa protein only in susceptible oat leaf slices. This in vivo binding was
      competitively displaced by reduced victorin, a nontoxic protective compound, and
      appeared to be correlated with biological activity. In vitro binding to the 100
      kDa protein in leaf extracts showed several differences from in vivo binding.
      Binding was not genotype specific and required a reducing agent that was not
      required for in vivo binding. Differential centrifugation showed that the 100-kDa
      victorin binding protein was not a cytosolic protein but was enriched in a high
      speed particulate fraction. The data support the hypothesis that the 100-kDa
      protein is the victorin receptor.

PMID- 16594051
TI  - The chloroplast genome exists in multimeric forms.
AB  - Chloroplast DNA conformation was analyzed by pulse-field gel electrophoresis. We
      found that spinach leaf chloroplast DNA molecules exist in at least four distinct
      forms with the apparent molecular weights of monomer, dimer, trimer, and
      tetramer. Two-dimensional gel analysis of DNA after UV nicking and in the
      presence of ethidium bromide indicates that they are not isomers that differ in
      superhelical density. DNA gyrase decatenation analysis demonstrates that the
      majority of the DNA molecules are oligomers rather than catenanes. The relative
      amounts of monomer, dimer, trimer, and tetramer forms, quantitated by molecular
      hybridization, are 1, 1/3, 1/9, and 1/27, respectively, and do not change during
      leaf maturation. The possible mechanisms of chloroplast DNA oligomer formation
      are discussed.

PMID- 16594050
TI  - New World tetraploid cottons contain Old World cytoplasm.
AB  - New World tetraploid cottons (Gossypium spp.) originated through hybridization of
      ancestral diploid species that presently have allopatric ranges in Asia-Africa
      (the A genome) and the New World tropics and subtropics (the D genome). Despite
      intensive study, the identity of the parental diploids and the antiquity of
      polyploidization remain unresolved. In this study, variation in the maternally
      inherited chloroplast genome was assessed among species representing both of the
      parental genomes and the tetraploids. Approximately 560 restriction sites were
      assayed in each accession, representing sequence information for about 3200
      nucleotides. The resulting maternal phylogeny has no convergent restriction site
      mutations and demonstrates that the cytoplasm donor for all tetraploid species
      was an A genome diploid with a chloroplast genome that is similar to Gossypium
      arboreum and Gossypium herbaceum. No mutational differences were detected between
      these two species, and few mutations distinguish the chloroplast genomes of A
      genome diploids from those of tetraploid taxa. In contrast to expectations based
      on extensive taxonomic, geographic, and genetic diversity, a surprisingly low
      level of sequence divergence has accumulated subsequent to polyploidization.
      Chloroplast genomes of tetraploid species are distinguished from each other by
      between one and six apparent point mutations. The data suggest that tetraploid
      cotton originated relatively recently, perhaps within the last 1-2 million years,
      with subsequent rapid evolution and diversification throughout the New World
      tropics.

PMID- 16594052
TI  - Functional expression of plant acetolactate synthase genes in Escherichia coli.
AB  - Acetolactate synthase (ALS; EC 4.1.3.18) is the first common enzyme in the
      biosynthetic pathways leading to leucine, isoleucine, and valine. It is the
      target enzyme for three classes of structurally unrelated herbicides, the
      sulfonylureas, the imidazolinones, and the triazolopyrimidines. A cloned ALS gene
      from the small cruciferous plant Arabidopsis thaliana has been fused to bacterial
      transcription/translation signals and the resulting plasmid has been used to
      transform Escherichia coli. The cloned plant gene, which includes sequences
      encoding the chloroplast transit peptide, is functionally expressed in the
      bacteria. It is able to complement genetically a strain of E. coli that lacks
      endogenous ALS activity. An ALS gene cloned from a line of Arabidopsis previously
      shown to be resistant to sulfonylurea herbicides has been similarly expressed in
      E. coli. The herbicide-resistance phenotype is expressed in the bacteria, as
      assayed by both enzyme activity and the ability to grow in the presence of
      herbicides. This system has been useful for purifying substantial amounts of the
      plant enzyme, for studying the sequence parameters involved in subcellular
      protein localization, and for characterizing the interactions that occur between
      ALS and its various inhibitors.

PMID- 16594054
TI  - Trapped individual ion at absolute zero temperature.
AB  - Laser cooling and ion trapping have progressed to such an extent that one can now
      speak of realizing a confined atom at absolute zero temperature. In this short
      publication, we analyze an experiment toward such realization using a single
      Ba(+) ion in a miniature rf trap. The Ba(+) ion is first laser-cooled to the
      limit where the ion spends most of its time in the zero-point energy state. Then
      a test sequence allows one to verify whether or not the ion is actually in its
      zero-point state. The test sequence may also serve as a device for state
      selection of an atom at absolute zero temperature.

PMID- 16594053
TI  - Is there an excitonic interaction or antenna system in bacteriorhodopsin?
AB  - The presence of a biphasic circular dichroism (CD) observed in the visible
      absorption spectrum of retinal in bacteriorhodopsin (bR) has been believed for
      many years to be due to excitonic-type interaction within the trimeric structure
      of the retinal in the protein membrane. In the present work, we present data and
      discuss previous observations that strongly suggest the absence of such an
      excitonic interaction. The magnetic CD spectrum of the trimer is found to be
      similar to that of the monomer and shows no sign of absorption to the doubly
      degenerate state predicted to be present from the exciton theory. This, together
      with the previous observations on the CD spectra of the photocycle intermediates
      of bR as well as the linear polarization studies of the fluorescence and the
      daughter absorption, sheds doubt on the presence of exciton interaction and thus
      suggests the presence of neither an antenna system nor a viable special reaction
      center in bR. Possible explanation for the observed biphasic nature of the CD
      spectrum is given in terms of having more than one type of bR with different
      protein conformations around the retinals in the trimer giving each similar
      absorption maximum but opposite signs for its rotary dispersion power.

PMID- 16594055
TI  - Miniature Paul-Straubel ion trap with well-defined deep potential well.
AB  - In some recently proposed experiments using ion traps, a Paul trap of
      conventional size and design is insufficient. We have constructed a miniature
      Paul-Straubel trap. It has a small elliptic ring ( approximately 0.2 mm) and
      three pairs of planar electrodes ( approximately 2 cm part) arranged so that they
      form a cube. The two conventional end-cap electrodes are replaced by the six
      planar electrodes. The ring is heatable to a high temperature for improving the
      uniformity of the dc potential on the ring surface. With this trap, we hope to do
      such fundamental studies as the true zero-point confinement of a single ion.

PMID- 16594056
TI  - Self-assembly of synthetic phytochrome holoprotein in vitro.
AB  - The phytochrome holoprotein of plants requires a covalently bound linear
      tetrapyrrole (bilin) prosthetic group for its photoreceptor function. Here we
      show that synthetic phytochrome apoprotein prepared by transcription and
      translation of an Avena phytochrome cDNA construct combines in vitro with
      phycocyanobilin, an analog of the natural chromophore, to produce a photoactive
      holoprotein. These results indicate that holoprotein assembly is an
      "autocatalytic" process.

PMID- 16594057
TI  - Altered regulation of beta-amylase activity in mutants of Arabidopsis with
      lesions in starch metabolism.
AB  - Three classes of mutants of Arabidopsis thaliana (L.) Heynhold with alterations
      in starch metabolism were found to have higher levels of leaf amylase activity
      than the wild type when grown in a 12-hr photoperiod. This effect was dependent
      upon the developmental stage of the plants and was largely suppressed during
      growth in continuous light. The various amylolytic activities in crude extracts
      were separated by electrophoresis in nondenaturing polyacrylamide gels and
      visualized by activity staining. The increased amylase activity in the mutants
      was due to an up to 40-fold increase in the activity of an extrachloroplast beta
      amylase (EC 3.2.1.2). These observations indicate the existence of a regulatory
      mechanism that controls the amount of beta-amylase activity in response to
      fluctuations in photosynthetic carbohydrate metabolism. It is paradoxical that
      beta-amylase appears to be a highly regulated enzyme, but as yet no
      physiologically relevant function can be assigned to this enzyme due to the
      absence of starch in the cytoplasmic compartment of leaf cells.

PMID- 16594058
TI  - Different a alleles of Ustilago maydis are necessary for maintenance of
      filamentous growth but not for meiosis.
AB  - Two loci (the incompatibility or mating type loci), a and b, govern the life
      cycle of Ustilago maydis, a fungal pathogen of corn. U. maydis diploids
      heterozygous at both a and b (a[unk] b[unk]) form mycelial colonies (Fuz(+)
      phenotype), induce tumors, and produce teliospores able to undergo meiosis. We
      report here the isolation and characterization of nonmycelial (Fuz(-))
      derivatives. These Fuz(-) diploids have allowed us to examine the requirement of
      a[unk] and b[unk] in maintenance of filamentous growth and tumor-inducing
      ability. The Fuz(-) diploids are of four classes: two are inferred to be
      homozygous for b (a[unk] b=); the other two are shown to be homozygous for a (a=
      b[unk]). These observations confirm the requirement for b[unk] and reveal the
      requirement for a[unk] in filamentous growth. U. maydis is thus like other
      basidiomycetes that have two loci governing growth of the dikaryotic filament.
      The mating behavior of the Fuz(-) diploids indicates that heterozygosity at a or
      b does not block mating. Although both a= b[unk] and a[unk] b= diploids are
      nonmycelial, they differ in that a[unk] b= diploids are nonpathogenic, whereas a=
      b[unk] diploids are pathogenic and produce teliospores able to undergo meiosis.
      These findings substantiate previous, more limited observations. They demonstrate
      that ability to induce tumors and produce normal teliospores requires different
      alleles at b but not at a.

PMID- 16594059
TI  - Arsonium compounds in algae.
AB  - Search for a precursor of the arsenobetaine discovered in Western Australian rock
      lobster tail muscle has led to an algal metabolite of radioarsenate having the
      properties of a trimethylarsoniumriboside derivative of the major arsenicals of
      aquatic plants, dimethylarsinoylribosylglycerol, its sulfate ester, and the
      corresponding riboside of phosphatidylglycerol. Such an arsonium compound could
      serve as metabolic precursor of arsenobetaine, the innocuous arsenical component
      of many marine food products. The oceanic diatom, Chaetoceros gracilis, cultured
      in radioarsenate produced a compound whose chemical, chromatographic, and
      electrophoretic properties are described. It was found to be identical to the
      trimethylarsonium derivative synthesized from the major algal arsenical, 1-(5'
      dimethylarsinoyl-5'-deoxyribosyl)glycerol-3-O -sulfate.

PMID- 16594060
TI  - Photoaffinity labeling of indole-3-acetic acid-binding proteins in maize.
AB  - The photoaffinity labeling agent 5-azidoindole-3-acetic acid, an analog of the
      endogenous plant hormone indole-3-acetic acid (an auxin), was used to identify
      indole-3-acetic acid-binding proteins in maize. Two peptides with subunit
      molecular masses of 24 and 22 kilodaltons are specifically labeled in a saturable
      manner. Both peptides are slightly acidic and behave as dimers under
      nondenaturing conditions. The possibility that one of these peptides is the auxin
      receptor that mediates cell elongation in maize is discussed.

PMID- 16594061
TI  - Colony formation from mesophyll protoplasts of a cereal, oat.
AB  - Differentiated leaf cells of gramineous plants, among them the cereals with their
      immense importance for human nutrition, are considered extremely recalcitrant to,
      if not incapable of, reentering the cell cycle. This recalcitrance is related to
      the poor wound response of the monocots-in contrast to most dicots-and the
      difficulties encountered in monocot tissue culture. We report here the highly
      reproducible induction of sustained divisions at high frequency (up to 95%) and
      colony formation from mesophyll protoplasts of a cereal, oat, demonstrating that
      contrary to most earlier evidence-mesophyll cells of a gramineous plant have not
      irreversibly lost their potential for cell division.

PMID- 16594062
TI  - Selenium deficiency induced by zinc deprivation in a crustacean.
AB  - For intact daphnids reared in circumstances of controlled trace element exposure,
      one consequence of insufficient zinc (Zn) is an increased demand on the animal's
      pool of available selenium (Se). This demand is manifested by the type of cuticle
      deterioration associated with Se deficiency and by a depression of reproduction.
      In the presence of 25 parts per billion (ppb) Zn, 1 ppb Se eliminates these
      symptoms. In the absence of detectable Zn, 5 ppb Se eliminates overt cuticle
      damage and substantially increases reproduction. A shortening of life span
      resulting from Zn deprivation is not ameliorated by Se addition. We suggest that
      the interplay between Zn and Se concentrations reflects an underlying interplay
      between interdependent, but distinct, metabolic pathways; i.e., (for Se)
      glutathione peroxidase and (for Zn) Cu,Zn-superoxide dismutase-each offering
      protection against free radical damage. Because they are not necessarily
      localized in a given tissue, the key to recognition of such subtle, complex trace
      nutrient interactions has been use of intact animals in circumstances of control
      previously attainable only in tissue cultures.

PMID- 16594063
TI  - Quantum simulation of nuclear rearrangement in electron transfer reactions.
AB  - A quantum simulation scheme based on the path integral molecular dynamics
      technique has been used to calculate the effective activation energies associated
      with nuclear rearrangement in the electron transfer reactions Co(NH(3))(6) (2+) +
      Co(NH(3))(6) (3+) --> Co(NH(3))(6) (3+) + Co(NH(3))(6) (2+) and Ru(NH(3))(6) (2+)
      + Ru(NH(3))(6) (3+) --> Ru(NH(3))(6) (3+) + Ru(NH(3))(6) (2+). Even with a simple
      Hamiltonian and short time dynamic simulations, the results are in satisfactory
      agreement with other theoretical calculations. This simulation approach can be
      used in chemical and biological systems where the reactions are largely
      controlled by nuclear rearrangements, such as those of electron transfer
      reactions in some electron carrier proteins.

PMID- 16594064
TI  - Critical shape transitions of monolayer lipid domains.
AB  - Fluorescence microscopy can be used to visualize coexisting fluid phases in lipid
      monolayers composed of cholesterol and dipalmitoyl phosphatidylcholine under
      specified conditions of temperature, composition, and lateral pressure. At a
      critical composition of approximately 30 mol% cholesterol, decreasing the average
      molecular area below a(c) [unk]50 A(2) per molecule forces the binary mixture
      through a critical point, where the monolayer becomes homogeneous. At molecular
      areas approximately 10% above this critical area, we observe shape transitions
      from liquid domains with circular shapes to domains with less symmetrical shapes.
      Shape transitions and critical shape fluctuations can also be triggered with
      light, due to photochemical effects on the monolayer. Shape fluctuations of lipid
      domains can thus be used to sense chemical events at the air-water interface.

PMID- 16594065
TI  - Genetically engineered mutant of the cyanobacterium Synechococcus PCC 7942
      defective in nitrate transport.
AB  - Nitrate-grown cells of Synechococcus PCC 7942 (Anacystis nidulans R2) contain a
      45-kDa protein as a major protein in the cytoplasmic membrane but ammonium-grown
      cells lack it. A mutant (M45) was constructed by inactivating the gene encoding
      the 45-kDa protein. M45 did not grow under low concentrations of nitrate but high
      concentrations of nitrate could support its growth, with the optimal
      concentration being 40-70 mM. The growth rate of M45 was as high as that of the
      wild-type cells when ammonium was the nitrogen source. The 45-kDa protein was
      absent in M45 irrespective of the growth conditions. The activities of nitrate
      and nitrite reductases were higher in M45 than in wild type. The rate of nitrate
      dependent O(2) evolution in wild type measured in the presence of L-methionine
      D,L-sulfoximine and D,L-glyceraldehyde showed saturation kinetics with respect to
      nitrate concentration in the external medium. The nitrate concentration required
      to produce half the maximal rate was 1 muM. In M45, the rate of nitrate-dependent
      O(2) evolution was nearly zero at nitrate concentrations <1 mM and was linearly
      increased as the concentration increased. The presumed absence of nitrate
      transport in M45 demonstrated by these results suggested that the 45-kDa protein
      is a nitrate transporter.

PMID- 16594066
TI  - Regulation of anthocyanin biosynthetic genes introduced into intact maize tissues
      by microprojectiles.
AB  - We have employed microprojectiles to deliver genes involved in anthocyanin
      biosynthesis to cells within intact aleurone and embryo tissues of maize. Clones
      of the A1 or Bz1 genes were introduced into aleurone tissue that lacked
      anthocyanins due to mutations of the endogenous A1 or Bz1 gene. Following
      bombardment, cells within the aleurone developed purple pigmentation, indicating
      that the mutation in the a1 or bz1 genotypes was corrected by the introduced
      gene. To analyze the expression of these genes in different genetic backgrounds,
      chimeric genes containing the 5' and 3' regions of the A1 or Bz1 genes fused to a
      luciferase coding region were constructed. These constructs were introduced into
      aleurones of genotypes carrying either dominant or recessive alleles of the C1
      and R genes, which are known to regulate anthocyanin production. Levels of
      luciferase activity in permissive backgrounds (C1, R) were 30- to 200-fold
      greater than those detected in tissue carrying one or both of the recessive
      alleles (c1, r) of these genes. These results show that genes delivered to intact
      tissues by microprojectiles are regulated in a manner similar to the endogenous
      genes. The transfer of genes directly to intact tissues provides a rapid means
      for analyzing the genetic and tissue-specific regulation of gene expression.

PMID- 16594067
TI  - What is molt-inhibiting hormone? The role of an ecdysteroidogenesis inhibitor in
      the crustacean molting cycle.
AB  - The in vivo molt-inhibitory effects of the ecdysone biosynthesis inhibitors 3
      hydroxy-L-kynurenine and xanthurenic acid were investigated. These ecdysone
      biosynthesis inhibitors, isolated from the eyestalks of blue crabs (Callinectes
      sapidus), were injected into eyestalk-ablated crayfish (Procambarus clarkii). The
      active factor was found to be species-nonspecific within crabs and crayfish. The
      seasonal profiles of the xanthurenic acid and ecdysone titers exhibited a
      staggered relationship. Moreover, the activity of a 3-hydroxy-L-kynurenine
      aminotransferase varied during the molting cycle. The data suggested that 3
      hydroxy-L-kynurenine, which is secreted from the X-organ-sinus gland complex of
      crustaceans, is released into the hemolymph, and after accumulating at the
      surface of the Y-organ, is converted into the active form, xanthurenic acid.
      Xanthurenic acid was found to profoundly repress ecdysteroidogenesis in vitro.

PMID- 16594068
TI  - Critical size and curvature of wave formation in an excitable chemical medium.
AB  - The critical radius for the outward propagation of waves in an excitable solution
      of the Belousov-Zhabotinskii reaction was experimentally analyzed and found to be
      approximately 20 mum, being in a range predicted by theory. Thus, the wave
      initiation depends on the critical radius in an all-or-none fashion. For waves
      having high positive curvature of wave fronts, a linear relationship between the
      curvature and their normal velocity was established, allowing computation of a
      diffusion coefficient of 1.9 x 10(-5) cm(2)/s for the autocatalytic species,
      which agrees well with results previously obtained for negatively curved wave
      fronts. The analysis of the dispersion of wave velocity yielded the decrease of
      wave velocity for small initiation periods as predicted theoretically.

PMID- 16594069
TI  - Phytochelatins, the heavy-metal-binding peptides of plants, are synthesized from
      glutathione by a specific gamma-glutamylcysteine dipeptidyl transpeptidase
      (phytochelatin synthase).
AB  - An enzyme has been discovered and characterized from Silene cucubalus cell
      suspension cultures that catalyzes the transfer of the gamma-glutamylcysteine
      dipeptide moiety of glutathione to an acceptor glutathione molecule or a growing
      chain of [Glu(-Cys)](n)-Gly oligomers, thus synthesizing phytochelatins, the
      metal-binding peptides of higher plants and select fungi. The enzyme was named
      gamma-glutamylcysteine dipeptidyl transpeptidase and given the trivial name
      phytochelatin synthase. The primary reaction catalyzed is [Glu(-Cys)]-Gly + [Glu(
      Cys)](n)-Gly --> [Glu(-Cys)](n+1)-Gly + Gly. The enzyme is isoelectric near pH
      4.8 and has temperature and pH optima at 35 degrees C and 7.9, respectively.
      Phytochelatin synthase is constitutively present in cell cultures of various
      plant species and its formation is not noticeably induced by heavy metal ions in
      the growth medium. The enzyme (M(r)95,000) seems to be composed of four subunits,
      the dimer (M(r)50,000) being also catalytically active. Cd(2+) is by far the best
      metal activator of the enzyme followed by Ag(+), Bi(3+), Pb(2+), Zn(2+), Cu(2+),
      Hg(2+), and Au(+). The K(m) for glutathione is 6.7 mM. The enzyme activity seems
      to be self-regulated in that the product of the reaction (the phytochelatins)
      chelates the enzyme-activating metal, thus terminating the enzyme reaction. The
      molar ratio of the gamma-glutamylcysteine dipeptide in phytochelatin to Cd(2+) in
      the newly formed complex was 2:1.

PMID- 16594070
TI  - Multiplier ideal sheaves and existence of Kahler-Einstein metrics of positive
      scalar curvature.
AB  - To study C(0)a priori estimates for solutions to certain complex Monge-Ampere
      equations, I introduce a coherent sheaf of ideals and show that it satisfies
      various global algebrogeometric conditions, including a cohomology vanishing
      theorem. This technique is used to establish the existence of Kahler-Einstein
      metrics of positive scalar curvature on a very large class of compact complex
      manifolds.

PMID- 16594071
TI  - Wounding induces the first enzyme of the shikimate pathway in Solanaceae.
AB  - The first enzyme of the shikimate pathway, 3-deoxy-D-arabino-heptulosonate-7
      phosphate synthase (EC 4.1.2.15), is induced by wounding potato or tomato tissue.
      The increase in enzyme activity is associated with elevated amounts of the enzyme
      as determined by immunoblots. The specific wound-induced protein synthesis is
      preceded by an increase in the mRNA encoding this enzyme. The induced mRNA of
      potato tuber, leaf, and stem tissue is translated into a precursor polypeptide
      that is recognized by antibodies raised against the mature enzyme from tuber
      plastids. Wounding also induces mRNA encoding phenylalanine ammonia-lyase (EC
      4.3.1.5), a key enzyme of plant secondary metabolism. The time courses for the
      induction of the two enzymes are similar, suggesting coordinate regulation for
      the biosynthesis of primary and secondary aromatic compounds.

PMID- 16594072
TI  - Maize nuclear background regulates the synthesis of a 22-kDa polypeptide in Zea
      luxurians mitochondria.
AB  - When cytoplasm of the teosinte Zea luxurians is introduced into certain maize
      inbred nuclear backgrounds, the pattern of protein synthesis in the teosinte
      mitochondria is altered. Teosinte mitochondria purified from plants possessing a
      maize A619 nuclear background (Z.l.-A619 plants) synthesize a novel 22-kDa
      polypeptide that is associated exclusively with the membrane fraction of the
      organelle. Mitochondria from plants possessing a W23 nuclear background do not
      synthesize this protein. The F(1) hybrids Z.l.-A619 x W23 and Z.l.-W23 x A619 do
      not synthesize the protein. However, synthesis of the polypeptide was observed in
      14 of 21 individual progeny from the backcross of the F(1) hybrid Z.l.-A619 x W23
      to the pollen parent A619. These data suggest that a single nuclear gene controls
      the synthesis of the 22-kDa protein in mitochondria, with the recessive allele of
      the gene allowing expression of the polypeptide. Mitochondria from the F(1)
      hybrid Z.l.-A619 x Mo17 synthesize the 22-kDa protein, whereas mitochondria from
      Z.l.-A619 x B73 do not. Data from these outcrosses demonstrate that other maize
      lines also possess nuclear genes capable of regulating the synthesis of the 22
      kDa Zea luxurians mitochondrial protein.

PMID- 16594073
TI  - Inheritance and expression of foreign genes in transgenic soybean plants.
AB  - DNA-coated gold particles were introduced into meristems of immature soybean
      seeds using electric discharge particle acceleration to produce transgenic
      fertile soybean plants. The lineages of integrated foreign DNA in two
      independently transformed plants were followed in the first (R(1)) and second
      (R(2)) generation of self-pollinated progeny. One plant (4615) was transformed
      with the Escherichia coli genes for beta-glucuronidase and neomycin
      phosphotransferase II; the other (3993) was transformed only with the gene for
      beta-glucuronidase. Segregation ratios for the introduced gene(s) were
      approximately 3:1 for plant 4615 and 1:1 for plant 3993 in the R(1) generation.
      DNA analysis showed 100% concordance between presence of the foreign gene
      sequences and enzyme activity. Moreover, all copies of the foreign genes are
      inherited as a unit in each plant. Plant 3993 segregated in a 1:1 ratio in the
      R(2) generation. R(1) plants derived from plant 4615, which expressed both genes,
      gave either 100% or 3:1 expression of both genes in the R(2) generation,
      demonstrating recovery of both homozygous and heterozygous R(1) plants. Our
      results show that foreign DNA introduced into soybean plants using electric
      discharge particle acceleration can be inherited in a Mendelian manner. Results
      also demonstrate cotransformation of tandem markers and show that both markers
      are inherited as closely linked genes in subsequent generations. These results
      indicate that whole plants can be derived from single transformed cells by a de
      novo organogenic pathway.

PMID- 16594074
TI  - Quasi-random hypergraphs.
AB  - We describe a large equivalence class of properties shared by most hypergraphs,
      including so-called random hypergraphs. As a result, it follows that many global
      properties of hypergraphs are actually consequences of simple local conditions.

PMID- 16594075
TI  - The computation of classical constants.
AB  - Hypergeometric representations of classical constants and efficient algorithms
      for their calculation are discussed. Particular attention is devoted to
      algorithms for computing pi.

PMID- 16594076
TI  - Evidence that the adverse effect of urea fertilizer on seed germination in soil
      is due to ammonia formed through hydrolysis of urea by soil urease.
AB  - Studies using seeds of wheat (Triticum aestivum L.), rye (Secale cereale L.),
      barley (Hordeum vulgare L.), and corn (Zea mays L.) indicated that the adverse
      effect of urea fertilizer on seed germination in soil is due to ammonia formed
      through hydrolysis of urea by soil urease and is not due to urea itself, to urea
      fertilizer impurities such as biuret, or to nitrite formed by nitrification of
      urea nitrogen. Support for this conclusion was obtained from (i) comparison of
      the effects on seed germination in soil of purified urea, urea fertilizers, urea
      fertilizer impurities, and compounds formed by enzymatic and microbial
      transformations of urea in soil; (ii) studies showing that ammonia volatilized
      from soils treated with urea completely inhibited germination of seeds close to,
      but not in contact with, these soils; and (iii) experiments showing that the
      adverse effect of urea fertilizer on seed germination in soil was completely
      eliminated when the soil was autoclaved to destroy urease or was treated with
      phenylphosphorodiamidate to inhibit soil urease activity before treatment with
      urea fertilizer.

PMID- 16594077
TI  - Phytotoxicity of foliar-applied urea.
AB  - Recent work in our laboratory showed that the adverse effect of urea fertilizer
      on seed germination and seedling growth in soil is due to ammonia produced
      through hydrolysis of urea by soil urease (NH(2)CONH(2) + H(2)O --> 2NH(3) +
      CO(2)) and can be eliminated by amending the fertilizer with a small amount of a
      urease inhibitor such as phenylphosphorodiamidate. Because the leaf-tip necrosis
      often observed after foliar fertilization of plants with urea is usually
      attributed to ammonia formed through hydrolysis of urea by plant urease, we
      studied the possibility that this necrosis could be eliminated or reduced by
      adding phenylphosphorodiamidate to the urea fertilizer. We found that, although
      addition of this urease inhibitor to foliar-applied urea increased the urea
      content and decreased the ammonia content and urease activity of soybean [Glycine
      max. (L.) Merr.] leaves fertilized with urea, it increased the leaf-tip necrosis
      observed after fertilization. We conclude that this necrosis resulted from
      accumulation of toxic amounts of urea rather than from formation of toxic amounts
      of ammonia. This conclusion was supported by our finding that the necrotic areas
      of soybean leaves treated with urea or with urea and phenylphosphorodiamidate
      contained much higher concentrations of urea than did the nonnecrotic areas.

PMID- 16594078
TI  - Icosahedral quasicrystals of intermetallic compounds are icosahedral twins of
      cubic crystals of three kinds, consisting of large (about 5000 atoms) icosahedral
      complexes in either a cubic body-centered or a cubic face-centered arrangement or
      smaller (about 1350 atoms) icosahedral complexes in the beta-tungsten
      arrangement.
AB  - The twofold-axis electron-diffraction photographs of icosahedral quasicrystals
      are of three kinds, reflecting three different structures of the cubic crystals
      that by icosahedral twinning form the quasicrystals. The first kind, represented
      by Al(13)Cu(4)Fe(3), contains two very large icosahedral complexes, each of about
      4680 atoms, in the body-centered arrangement, with six smaller icosahedral
      complexes (104 atoms each) in the principal interstices. The second kind,
      represented by Al(5)Mn, contains four of the very large complexes in the face
      centered arrangement (cubic close packing), with four of the smaller clusters in
      the interstices. The third kind, represented by Al(6)CuLi(3), contains eight
      icosahedral complexes, each of about 1350 atoms, in the beta-W arrangement. The
      supporting evidence for these cubic structures is discussed as well as other
      evidence showing that the simple quasicrystal theory, which states that
      quasicrystals do not involve any translational identity operations, has to be
      modified.

PMID- 16594080
TI  - Search for deep slabs in the Northwest Pacific mantle.
AB  - A residual sphere is formed by projecting seismic ray travel-time anomalies,
      relative to a reference Earth model, onto an imaginary sphere around an
      earthquake. Any dominant slab-like fast band can be determined with spherical
      harmonic expansion. The technique is useful in detecting trends associated with
      high-velocity slabs beneath deep earthquakes after deep-mantle and near-receiver
      effects are removed. Two types of corrections are used. The first uses a
      tomographic global mantle model; the second uses teleseismic station averages of
      residuals from many events over a large area centered on the events of interest.
      Under the Mariana, Izu-Bonin, and Japan trenches, the dominant fast bands are
      generally consistent with seismicity trends. The results are unstable and differ
      from the seismicity trend for Kurile events. The predominant fast band for most
      deep earthquakes under Japan is subhorizontal rather than near vertical. We find
      little support for the deep slab penetration hypothesis.

PMID- 16594079
TI  - Comment on a paper by Linus Pauling.

PMID- 16594081
TI  - The cyclotomic trace and the K-theoretic analogue of Novikov's conjecture.
AB  - A trace construction, the cyclotomic trace, is given. It associates to algebraic
      K-theory of a group ring, or better to Waldhausen's A-theory, equivariant stable
      homotopy classes of the free-loop space of its classifying space. The cyclotomic
      trace detects the Borel classes in algebraic K-theory of the integers. It is used
      to prove, for a wide class of groups, that the K-theory assembly map is
      rationally injective. This is the K-theoretic analogue of Novikov's conjecture.

PMID- 16594082
TI  - Solutions to Yang-Mills equations that are not self-dual.
AB  - The Yang-Mills functional for connections on principle SU(2) bundles over S(4) is
      studied. Critical points of the functional satisfy a system of second-order
      partial differential equations, the Yang-Mills equations. If, in particular, the
      critical point is a minimum, it satisfies a first-order system, the self-dual or
      anti-self-dual equations. Here, we exhibit an infinite number of finite-action
      nonminimal unstable critical points. They are obtained by constructing a
      topologically nontrivial loop of connections to which min-max theory is applied.
      The construction exploits the fundamental relationship between certain invariant
      instantons on S(4) and magnetic monopoles on H(3). This result settles a question
      in gauge field theory that has been open for many years.

PMID- 16594083
TI  - Cold fusion in metals.
AB  - A simple model of a metal containing deuterons is considered. The example of
      palladium is treated in detail. It is shown that the effect of screening of
      Coulomb fields by conduction electrons is sufficient to allow deuteron pairs to
      fuse at rates of 10(-30) sec(-1), seven orders of magnitude smaller than those
      reported by Jones et al. [Jones, S. E., Palmer, E. P., Czirr, J. B., Decker, D.
      L., Jensen, G. L., Thorne, J. M., Taylor, S. F. & Rafelski, J. (1989) Nature
      (London) 388, 737-740].

PMID- 16594084
TI  - Triton,... electron,... cosmon,...: An infinite regression?
AB  - I propose an elementary particle model in which the simplest near-Dirac particles
      triton, proton, and electron are members of the three top layers of a bottomless
      stack. Each particle is a composite of three particles from the next layer below
      in an infinite regression approaching Dirac point particles. The cosmon, an
      immensely heavy lower layer subquark, is the elementary particle. The world-atom,
      a tightly bound cosmon/anticosmon pair of zero relativistic total mass, arose
      from the nothing state in a quantum jump. Rapid decay of the pair launched the
      big bang and created the universe.

PMID- 16594085
TI  - Mitochondrial responses to intracellular pulses of photosynthetic oxygen.
AB  - When submitting anaerobic algal cells to a series of saturating flashes,
      transient absorption changes of mitochondrial origin were detected, showing the
      characteristic flash-number dependence of photosynthetic oxygen evolution. The
      faster kinetic event is the oxidation of heme a(3) of the cytochrome-c oxidase,
      which reaches a maximum at [unk]3.5 ms before again being reduced within 20 ms.
      The oxidation of cytochrome c involves an initial submillisecond lag, and its
      half-time is [unk]3.3 ms. Another component, probably indicating oxidation of
      heme a, is seen around 607 nm, with a kinetic behavior similar to that of
      cytochrome c. The fast time scale of these reactions excludes long-range
      diffusion and supports a direct intracellular trapping of O(2). It is estimated
      that, under appropriate conditions, the yield of this process is >30%. The
      linearity of these responses with respect to the amplitude of the oxygen pulse
      implies that a single turnover of the cytochrome oxidase is involved. These
      results suggest that the intracellular oxygen pathway may be of physiological
      importance in green algae. On the other hand, this technique seems promising both
      as an alternative to polarographic detection of photosynthetic oxygen and as a
      means of studying the cytochrome oxidase response in vivo to single-turnover
      oxygen pulses.

PMID- 16594086
TI  - Plant responses to elevational gradients of O(3) exposures in Virginia.
AB  - In Shenandoah National Park, O(3) monitoring data were characterized and attempts
      were made to relate O(3) concentration levels to visible foliar injury observed
      for five plant species surveyed. Foliar injury for three species increased with
      elevation. The 24-h monthly mean O(3) concentrations tended to increase with
      elevation; however, the number of elevated hourly occurrences did not. Although
      the frequency of high hourly O(3) concentrations did not consistently increase
      with elevation, O(3) exposures in the park may have been high enough to provoke
      an effect that may have been enhanced by vegetation sensitivities that differed
      as a function of altitude.

PMID- 16594087
TI  - Forced convection modulates gas exchange in cnidarians.
AB  - Boundary layer thickness is a potentially important component of the diffusive
      pathway for gas exchange in aquatic organisms. The soft coral Alcyonium siderium
      (Octocorallia) and sea anemone Metridium senile (Actiniaria) exhibit significant
      increases in respiration with water flow over a range of Reynolds numbers
      encountered subtidally. A nondimensional mass transfer analysis of the effect of
      forced convection demonstrates the importance of the state of the organism's
      boundary layer in regulating metabolism in these invertebrates. Flow-modulated
      gas exchange may limit secondary productivity in subtidal environments.

PMID- 16594088
TI  - Ecological systems and the concept of biological organization.
AB  - An axiomatic system is proposed to improve identification, description, and
      analysis of complex ecological systems. Such systems are assumed to be organized
      and have structure. Organization is the complex of interactions and properties of
      structure that make the perpetuation of structure possible. An entity of
      structure is assumed to be composed of other entities. The term entity is adopted
      as a "primitive term." The concept of minimum interactive structure is imposed as
      an epistemological constraint on the structural infinity of real systems. Other
      terms are defined as either relations between entities of structure, derived
      properties resulting from combining such entities into entities of higher order,
      or conditions necessary for this assembly. Organization is a composite term and
      consists of complementarity, coordination, integration, and hierarchy. Evaluation
      of overall organization of an ecological entity appears theoretically possible
      through parametrization and quantification of these components of organization.

PMID- 16594089
TI  - Gene flow by pollen into small populations: Data from experimental and natural
      stands of wild radish.
AB  - Gene flow can have an especially strong impact on the evolution of small
      populations. However, empirical studies on the actual rates and patterns of gene
      flow into small populations are few. Thus, we sought to measure gene flow into
      small populations of wild radish. Raphanus sativus. We found significant
      differences in gene flow receipt among experimental populations and within those
      populations over a season. A maximum-likelihood estimate revealed that almost all
      of the gene flow into these synthetic populations had its origin in relatively
      distant (>650 m), large natural populations rather than the proximal (255-400 m),
      small synthetic populations. We also estimated rates of interpopulation mating
      from simple paternity analysis of progeny produced by seven small (ca. 50 plants)
      natural populations. Again, we found significant heterogeneity in gene flow
      receipt. Although these populations varied 10-fold in their range of isolation
      distances (100-1000 m), gene flow rates did not vary with distance. The magnitude
      of gene flow rates estimated in all but one population was great enough for gene
      flow to play an important role in the evolution of these small populations.

PMID- 16594090
TI  - Bleaching in reef corals: Physiological and stable isotopic responses.
AB  - During the late summer to fall of 1987, Caribbean reef corals experienced an
      intense and widespread discoloration event described as bleaching. Contrary to
      initial predictions, most bleached corals did not die. However, energy input from
      zooxanthellae decreased, as estimated from: (i) delta(13)C values, a measure of
      the discrimination against (13)C in (12)C/(13)C assimilation, of skeletal
      aragonite; (ii) in situ photosynthesis-irradiance measurements; (iii) and tissue
      biomass parameters of Montastraea annularis and Agaricia lamarcki. The delta(18)O
      signal, a measure of the discrimination against (18)O in (16)O/(18)O
      assimilation, from M. annularis skeletons demonstrated that this event coincided
      with abnormally elevated water temperatures.

PMID- 16594091
TI  - Chloroplast and mitochondrial DNA are paternally inherited in Sequoia
      sempervirens D. Don Endl.
AB  - Restriction fragment length polymorphisms in controlled crosses were used to
      infer the mode of inheritance of chloroplast DNA and mitochondrial DNA in coast
      redwood (Sequoia sempervirens D. Don Endl.). Chloroplast DNA was paternally
      inherited, as is true for all other conifers studied thus far. Surprisingly, a
      restriction fragment length polymorphism detected by a mitochondrial probe was
      paternally inherited as well. This polymorphism could not be detected in
      hybridizations with chloroplast probes covering the entire chloroplast genome,
      thus providing evidence that the mitochondrial probe had not hybridized to
      chloroplast DNA on the blot. We conclude that mitochondrial DNA is paternally
      inherited in coast redwood. To our knowledge, paternal inheritance of
      mitochondrial DNA in sexual crosses of a multicellular eukaryotic organism has
      not been previously reported.

PMID- 16594092
TI  - Icosahedral and decagonal quasicrystals of intermetallic compounds are multiple
      twins of cubic or orthorhombic crystals composed of very large atomic complexes
      with icosahedral point-group symmetry in cubic close packing or body-centered
      packing: Structure of decagonal Al(6)Pd.
AB  - A doubly icosahedral complex involves roughly spherical clusters of atoms with
      icosahedral point-group symmetry, which are themselves, in parallel orientation,
      icosahedrally packed. These complexes may form cubic crystallites; three
      structures of this sort have been identified. Analysis of electron diffraction
      photographs of the decagonal quasicrystal Al(6)Pd has led to its description as
      involving pentagonal twinning of an orthorhombic crystal with a = 51.6 A, b =
      37.6 A, and c = 33.24 A, with about 4202 atoms in the unit, comprising two 1980
      atom doubly icosahedral complexes, each involving icosahedral packing of 45 44
      atom icosahedral complexes (at 0 0 0 and 1/2 1/2 1/2) and 242 interstitial atoms.
      The complexes and clusters are oriented with one of their fivefold axes in the c
      axis direction.

PMID- 16594093
TI  - Abscisic acid is involved in the wound-induced expression of the proteinase
      inhibitor II gene in potato and tomato.
AB  - Plants respond to wounding or pathogen attack by a variety of biochemical
      reactions, involving in some instances gene activation in tissues far apart from
      the actual site of wounding or pathogen invasion. One of the best analyzed
      examples for such a systemic reaction is the wound-induced expression of
      proteinase inhibitor genes in tomato and potato leaves. Local wounding of potato
      or tomato plants results in the accumulation of proteinase inhibitors I and II
      throughout the aerial part of the plant. In contrast to wild-type plants,
      abscisic acid-deficient mutants of potato (droopy) and tomato (sit) show a
      drastically reduced induction of these genes in response to plant wounding. High
      levels of proteinase inhibitor II gene expression are obtained in mutant and wild
      type plants upon exogenous application of abscisic acid. Measurements of the
      endogenous abscisic acid levels in wild-type plants show that wounding results in
      increased levels of this phytohormone in wounded and nonwounded systemically
      induced leaves. Thus these results show that the plant hormone abscisic acid is
      involved in the wound-induced activation of the proteinase inhibitor II gene.
      Furthermore, they are compatible with a model assuming this hormone to be the
      actual mediator of the systemic wound response.

PMID- 16594094
TI  - Dependence of the phototropic response of Arabidopsis thaliana on fluence rate
      and wavelength.
AB  - In the phototropic response of Arabidopsis thaliana seedlings, the shape of the
      fluence-response relation depends on fluence rate and wavelength. At low fluence
      rates, the response to 450-nm light is characterized by a single maximum at about
      0.3 mumol.m(-2). At higher fluence rates, the response shows two distinct maxima,
      I and II, at 0.3 and 3.5 mumol.m(-2), respectively. The response to 500-nm light
      shows a single maximum at 2 mumol.m(-2), and the response to 510-nm light shows a
      single maximum at 4.5 mumol.m(-2), independent of fluence rate. The response to
      490-nm light shows a maximal at 4.5 mumol.m(-2) and a shoulder at about 0.6
      mumol.m(-2). Preirradiation with high-fluence 510-nm light from above,
      immediately followed by unilateral 450-nm light, eliminates maximum II but not
      maximum I. Preirradiation with high-fluence 450-nm light from above eliminates
      the response to subsequent unilateral irradiation with either 450-nm or 510-nm
      light. The recovery of the response following high-fluence 450-nm light is
      considerably slower than the recovery following high-fluence 510-nm light.
      Unilateral irradiation with low-fluence 510-nm light followed by 450-nm light
      results in curvature that is approximately the sum of those produced by either
      irradiation alone. Based on these results, it is proposed that phototropism in A.
      thaliana seedlings is mediated by at least two blue-light photoreceptor pigments.

PMID- 16594095
TI  - Zoidogamy in fossil gymnosperms: The centenary of a concept, with special
      reference to prepollen of late Paleozoic conifers.
AB  - This year is the centenary of the surprising discovery in 1896 of zoidogamy in
      extant cycadophytes and Ginkgo. But by coincidence, also in the same year, the
      concept of prepollen was introduced. The morphology of prepollen was considered
      justification for the probable production of motile antherozoids in extinct
      gymnosperms. In this paper, the history of the prepollen concept is briefly
      outlined. It is emphasized that, in addition to well-known examples in
      pteridosperms and cordaitaleans, a prepollen condition also occurred among late
      Paleozoic conifers.

PMID- 16594096
TI  - Pediatricians endorse needle exchange.

PMID- 16594097
TI  - Global. UNAIDS: HIV/AIDS-infected children neglected.

PMID- 16594098
TI  - Disclosure. Court: air safety trumps HIV privacy in post-9/11 setting.

PMID- 16594099
TI  - Treatment. Virginia strives to improve HIV care for minorities.

PMID- 16594101
TI  - A diabetic man with a palpable abdominal wall mass.

PMID- 16594100
TI  - Discrimination. Lambda orchestrates resolutions in HIV-related disputes.

PMID- 16594102
TI  - First, do no harm: the use of covert video surveillance to detect Munchausen
      Syndrome by Proxy--an unethical means of "preventing" child abuse.
AB  - Since it was first identified in 1977, Munchausen Syndrome by Proxy has uniquely
      affected the way in which the medical and legal communities deal with the issue
      of child abuse. Inherent in the medical response to the disease are issues of
      suspicion, investigation, identification, confrontation, and, of course, the
      health of an innocent child. Given the deceptive dynamics of this disease,
      however, denial and disbelief naturally overshadow every action taken by medical
      professionals in pursuing these issues. Fortunately, as medical knowledge about
      the dynamics of the disease continues to develop, medical professionals become
      more willing and better able to identify the disease and focus their response on
      the safety of the child. The greatest problem in prosecuting Munchausen Syndrome
      by Proxy is that judges and juries remain unwilling to accept the reality of the
      disease. Consequently, in an effort to confirm medical suspicions and quell legal
      doubts, the medical community has resorted to covert video surveillance of the
      abuse while it is being perpetrated in the hospital. In this Article, Flannery
      argues that this response is an unnecessary and unethical, means of preventing
      Munchausen Syndrome by Proxy and protecting the child. Flannery supports the
      approach taken by the Family Court of New York in addressing Munchausen Syndrome
      by Proxy cases. The Family Court of New York recognizes the unique dynamics of
      this bizarre disorder, and, therefore, considers all cumulative circumstantial
      evidence in a Munchausen Syndrome by Proxy case, comparing the facts of the
      subject case to the commonly accepted features of confirmed cases. Part of the
      circumstantial evidence that should be considered, Flannery argues, is the
      dissipation of the child's condition upon temporary separation from the alleged
      perpetrating parent. As is done by the Flannery Court of New York, a res ipsa
      loquitur standard should then be applied, and an appropriate disposition for the
      child should be determined. By employing this standard, the court may confirm
      suspicions of Munchausen Syndrome by Proxy while avoiding the unnecessary harm to
      the child inherent in the covert video surveillance of Munchausen Syndrome by
      Proxy.

PMID- 16594104
TI  - Thyroid reports: insight into radioiodine ablation and new guidelines for nodule
      management.

PMID- 16594105
TI  - SNM 2006 Scientific Program explores expanding imaging technologies.

PMID- 16594103
TI  - Report on radiology medication errors provokes alarms, responses and
      recommendations.

PMID- 16594107
TI  - Constitutional law: parental denial of a child's medical treatment for religious
      reasons.

PMID- 16594106
TI  - Regulating research with decisionally impaired individuals: are we making
      progress?

PMID- 16594108
TI  - The rhetoric of disrespect: uncovering the faulty premises infecting reproductive
      rights.

PMID- 16594109
TI  - Tubing misconnections--a persistent and potentially deadly occurrence.

PMID- 16594111
TI  - Abstracts of the 10th Leipziger Workshop and the 3rd International Workshop on
      Slide-Based Cytometry, Liepzig, Germany, April 7-9, 2005.

PMID- 16594110
TI  - Consti-tortion: tort law as an end-run around abortion rights after Planned
      Parenthood v. Casey.

PMID- 16594112
TI  - The inapplicability of parental involvement laws to the distribution of
      mifepristone (RU-486) to minors.

PMID- 16594113
TI  - Fourteenth Amendment unenumerated rights jurisprudence: an essay in response to
      Stenberg v. Carhart.

PMID- 16594114
TI  - Sex selection: regulating technology enabling the predetermination of a child's
      gender.

PMID- 16594115
TI  - Dehydration and the elderly.

PMID- 16594116
TI  - The Best Pharmaceuticals for Children Act of 2002: the rise of the voluntary
      incentive structure and congressional refusal to require pediatric testing.
AB  - On January 4, 2002, President Bush signed into law the Best Pharmaceuticals for
      Children Act, which is the government's most comprehensive legislation regarding
      pediatric research to date. The Act offers pharmaceutical companies a six-month
      exclusivity term in return for their agreement to conduct pediatric tests on
      drugs. It also provides public funding and organizes private funding to help
      conduct pediatric research on those drugs that pharmaceutical companies opt not
      to test in children. This Note reviews the history of pediatric research and
      traces the development of the Best Pharmaceuticals for Children Act's unique
      incentive and public funding structure. The Note contends that, while the Act is
      comprehensive and promotes important pediatric studies, its incentive structure
      forces consumers and taxpayers to bear the costs of testing pharmaceuticals in
      children instead of the manufacturers who research, develop, and market those
      drugs. Congress should consider mandating pediatric studies in any future
      enactment of the legislation.

PMID- 16594117
TI  - Medicare drug benefit starts with complications.

PMID- 16594118
TI  - Proceedings and abstracts of the Annual Conference of the International Embryo
      Transfer Society, Copenhagen, Denmark, 8-12 January 2005.

PMID- 16594119
TI  - [Genetic aspects of rheumatoid arthritis].

PMID- 16594120
TI  - Proceedings of the workshop Ochratoxin A in Food: Recent Developments and
      Significance. Baden, Austria, 29 June-1 July 2005.

PMID- 16594121
TI  - Mechanisms in heart, lung, and vessel diseases. Proceedings of the 1st
      International Conference on Recent Advances in Biomedical and Therapeutic
      Sciences, January 13-15, 2004, Jhansi, India.

PMID- 16594122
TI  - The chair: low-tech device helps prevent pressure ulcers.

PMID- 16594123
TI  - Security of hazardous materials.

PMID- 16594125
TI  - Moody's: hospital outlook is stable for 2006; long term picture is uncertain.

PMID- 16594124
TI  - Practical ethics. Shopping for docs, drugs.

PMID- 16594126
TI  - [Clinical congress of the American College of Surgeons Announcement and
      Pittsburgh University Surgery Seminar Announcement supported by Japan Surgical
      Society--the American College of Surgeons Exchange Program].

PMID- 16594127
TI  - Cerebral oxygenation during repetitive apnea in newborn piglets.
AB  - This study examined the effect of repetitive apnea on brain oxygen pressure in
      newborn piglets. Each animal was given 10 episodes of apnea, initiated by
      disconnecting them from the ventilator and completed by reconnecting them to the
      ventilation circuit. The apneic episodes were ended 30 sec after the heart rate
      reached the bradycardic threshold of 60 beats per min. The oxygen pressure in the
      microvasculature of the cortex was measured by oxygen-dependent quenching of the
      phosphorescence. In all experiments, the blood pressure, body temperature, and
      heart rate were continuously monitored. Arterial blood samples were taken
      throughout the experiment and the blood pH, PaO2 and PaCO2 were measured. During
      pre-apnea, cortical oxygen was 55.1 +/- 6.4 (SEM, n = 7) mm Hg and decreased
      during each apnea to 8.1 +/- 2.8 mm Hg. However, the values of cortical oxygen
      varied during recovery periods. Maximal oxygen levels during recovery from the
      first two apneic episodes were 76.8 +/- 12 mm Hg and 69.6 +/- 9 mm Hg,
      respectively, values higher than pre-apnea. Cortical oxygen pressure then
      progressively decreased following consequent apnea. In conclusion, the data show
      that repetitive apnea caused a progressive decrease in cortical oxygen levels in
      the brain of newborn piglets. This deficit in brain oxygenation can be at least
      partly responsible for the neurological side effects of repetitive apnea.

PMID- 16594128
TI  - Optimal determination of detector placement in cerebral NIR spectroscopy of
      neonates using chemometric techniques.
AB  - This paper investigates the optimal placement of NIRS optodes in order to
      maximise the detection of haemoglobin changes in cortical grey matter resulting
      from an evoked response in neonates. The analysis is based upon predictions of
      optical signal at the surface of the head, using a Finite Element based model of
      light diffusion in tissue. Using the generated intensity data, the combination of
      optode positions, which maximise the signal from cortical grey matter whilst
      minimising that from surface tissue or cerebral white matter, is determined using
      a Chemometric statistical analysis. The neonatal head is modelled as a 2
      dimensional circle with 3 layers corresponding to the skin/scalp, and grey and
      white matter. A wide range of absorption coefficients for each layer is
      simulated, based upon physiologically reasonable values for parameters. Surface
      intensity at 10 different optode positions have been generated for a total of
      31,250 combinations of these variables for the 3 layers. It was found that with 3
      optodes at 5, 15, and 50 mm apart from the source, the smallest root-mean-square
      error between the estimated and modelled values can be obtained. Increasing the
      number of optodes further does not improve the performance.

PMID- 16594129
TI  - Simulation study of breast tissue hemodynamics during pressure perturbation.
AB  - We simulated the effects of compression of the breast on blood volume and tissue
      oxygenation. We sought to answer the question: how does the compression during
      breast examination impact on the circulatory systems of the breast tissue, namely
      blood flow, blood pooling, and oxygen concentration? We assumed that the blood
      was distributed in two compartments, arterial and venous. All the parameters were
      expressed with oxy- and deoxyhemoglobin quantities and were measured with a non
      invasive method, Near Infrared Spectroscopy (NIRS). The simulated data showed
      that the blood volume pool in the breast decreased due to lower arterial flow and
      higher venous outflow, as the breast was squeezed under 100 cm H2O with a 10 cm
      diameter probe (or 78 cm2). The blood volume was reversed when the pressure was
      released. The breast venous oxygen saturation dropped, but overall tissue
      saturation (presenting NIRS signal, volume weighted average saturation) was
      increased. The results showed that simulation can be used to obtain venous and
      average oxygen saturation as well as blood flow in compressed breast tissues.

PMID- 16594130
TI  - Microvascular oxygenation and oxidative stress during postischemic reperfusion.
      PO2, ROS, and NO during reperfusion.
AB  - Increased formation of ROS on reperfusion after ischemia underlies ischemia
      reperfusion (I/R) damage. We measured, in real time, both oxygen tension in
      microvessels and tissue and oxidant stress during postischemic reperfusion in
      hamster cheek pouch microcirculation. We measured PO2 by using phosphorescence
      quenching microscopy and oxygen radical species (ROS) production in the systemic
      blood. We evaluated the effects of a NOS inhibitor (L-NMMA) and superoxide
      dismutase (SOD) on the oxidative stress during reperfusion. Microvascular injury
      was assessed by measuring diameter change, the perfused capillary length (PCL),
      and leukocyte adhesion. Our findings demonstrate that early reperfusion is
      characterized by low concentration of oxygen linked to increased production of
      ROS. After this initial transience in arterioles, the oxygen tension and
      production of ROS return to normal after reperfusion, while the blood flow and
      capillary perfusion decrease. The early increased ROS production, in turn, may
      impair oxygen consumption by endothelial cells, thus further promoting activation
      of oxygen to ROS. This event is substantiated by the finding that treatment with
      SOD maintains ROS at normal levels, which, in turn, should be effective to
      increase the production of endothelial NO. Conversely, a decrease in NO levels
      led to decreased ROS production during early reperfusion, which increased later
      during reperfusion, ultimately causing vasoconstriction and greatly increasing
      venular leukocyte adhesion on postcapillary venules during hypoxic conditions.
      Therefore, low-flow hypoxia is primarily responsible for vascular endothelial
      damage during reperfusion through changes in ROS and NO production.

PMID- 16594131
TI  - Hypoxia, tumor endothelium, and targets for therapy.
AB  - Hypoxia is a well-recognized feature of human solid tumors. It is also well
      recognized, by both physicians and investigators, that malignant disease in
      various organs/tissues in the same patient, or the same tumor cells implanted in
      different sites or organs in the preclinical host, have different levels of
      hypoxia and different levels of response to systemic therapies. Over the past 10
      years, it has been established that normal cells involved in the malignant
      disease process can be important targets for therapeutic attack. A prime example
      of 'normal' cells that have come to the fore as anticancer therapeutic targets is
      endothelial cells. The field of antiangiogenic therapies was fueled by the early
      hypothesis which held that angiogenesis was the same no matter where it occurred.
      The corollary to this hypothesis was that models of normal embryo development, as
      well as models working with mature well-differentiated endothelial cells in
      culture, would be sufficient and satisfactory models for tumor endothelial cells.
      However, the current hypothesis is that angiogenesis occurring during malignant
      disease is abnormal, and that therapeutic targets identified by studying
      endothelial cells isolated from fresh samples of human cancers will be most
      relevant in developing therapeutic agents to treat human malignant disease.

PMID- 16594133
TI  - Effects of insulin and catecholamines on inotropy and oxygen uptake: best
      perfusate for skeletal muscles.
AB  - The purpose of this study is to identify the best perfusate after blood for
      maintaining skeletal muscle inotropy, muscle peak oxygen consumption (peak VO2),
      and oxygen consumption at rest (resting VO2) in in situ isolated canine
      gastrocnemius-plantaris muscle. Rejuvenated red cells suspended in perfusate at
      hematocrit 30% and 45%, perfusate contained insulin (100 microU x ml(-1)),
      adrenalin (0.3 and 3 ng x ml(-1)), and noradrenaline (3 ng x ml(-1)). Insulin
      significantly augmented resting VO2 and contracting muscle peak VO2, and
      developed isometric twitch tension at 4 Hz, compared with control. Insulin
      induced increase in resting muscle VO2 was abrogated by catecholamines. In
      addition to insulin and catecholamines, the developed twitch tension increased
      significantly by 178% with the accompanied increase in flow rate. O2 cost (peak
      VO2 / tension) significantly decreased by 52%. The developed tension did not
      correlate with O2 delivery but with flow rate and peak VO2 of contracting muscle.
      We successfully identified the characteristics of the best perfusate after blood.
      Our results suggest that the positive inotropy by insulin and catecholamines is
      attributed partly to an O2 delivery-independent increase in flow to contracting
      muscle and redistribution of flow within the contracting muscle, which suffered
      from low perfusion by perfusate containing rejuvenated red cells.

PMID- 16594132
TI  - Genetic oxygen sensor: GFP as an indicator of intracellular oxygenation.
AB  - We report in this article a new method for in vivo oxygen measurement using green
      fluorescence protein (GFP). COS7 cells were transiently transfected with an
      expression vector, pCMX-GFP, using a polyethylenimine reagent and cultured for 48
      hrs. After exposure of the cell to anoxic gas (O2 < .001%), a 1 min illumination
      of the cell to strong 470-490 nm light evoked a significant red fluorescence
      (excitation 520-550 nm, emission > 580 nm) that had been negligible before the
      photoactivation. This red shift of (green) GFP fluorescence was never observed in
      normoxia. We then examined the validity of this method in transgenic mice in
      which GFP is stably expressed (green mice). All the ventricular myocytes isolated
      from the green mice showed significant green fluorescence, although the intensity
      was approximately 1/200 of the transiently GFP-expressing COS7 cells. The
      photoactivation in anoxia increased the red fluorescence in these cells, but the
      magnitude was much smaller than expected. In summary, GFP can be used as an in
      situ probe for hypoxia. In GFP-expressing transgenic animals, in vivo imaging of
      anoxic loci with a submicron spatial resolution may be possible.

PMID- 16594134
TI  - Adaptation to chronic hypoxia during diet-induced ketosis.
AB  - It is recognized that brain oxygen deprivation results in increased glycolysis
      and lactate accumulation. Moreover, glucose metabolism is altered during
      starvation or diet, resulting in increased plasma ketones (acetoacetate + beta
      hydroxybutyrate; BHB). We investigated glucose and lactate adaptation to hypoxia
      in concurrence with diet-induced ketosis. Male Wistar rats were fed standard
      (STD), ketogenic (high fat; KG), or carbohydrate-rich (low fat; CHO) diets for 3
      wks and then exposed to hypobaric (0.5 ATM) or normobaric atmosphere for 3 wks
      while on their diets. Lactate, ketones, and glucose concentrations were measured
      in plasma (mM) and brain tissue (mmol/g). Plasma and tissue ketone levels were
      elevated up to 12-fold in the KG fed groups compared with other groups (STD and
      CHO), with the hypoxic KG group reaching the highest levels (2.6 +/- 1.3 mM and
      0.3 +/- 0.1 mmol/g; mean +/- SD). Tissue lactate levels in the hypoxic ketotic
      rats (4.7 +/- 1.3 mM) were comparable with normoxic STD (5.0 +/- 0.7 mM) and
      significantly lower (ANOVA P < .05) than the hypoxic STD rats (6.1 +/- 1.0 mM).
      These data indicate that adaptation to hypoxia did not interfere with ketosis,
      and that ketosis during hypoxia may lower lactate levels in brain, suggesting
      decreased glycolysis or increased glucose disposal.

PMID- 16594135
TI  - Varied response of spontaneous tumors to antiangiogenic agents.
AB  - Since conventional therapies are directly dependent on the supply of either drugs
      or oxygen, a key question is whether antiangiogenic agents produce detrimental
      effects on tumor vascular function, thus compromising combination therapies. A
      second question is whether experimental results based on fast-growing,
      transplanted tumors mimic those in slowly developing spontaneous tumors, which
      may be more representative of response in human primary tumors. To investigate
      changes in tumor pathophysiology, three antiangiogenic agents were compared: a)
      endostatin, b) anti-VEGFR-2 (DC101), and c) celecoxib. Total blood vessels were
      identified using anti-CD31, perfused vessels using DiOC7, and hypoxia by EF5
      uptake. Although individual tumor growth rates varied substantially, DC101
      produced the most striking inhibition. DC101 increased total and perfused vessel
      spacing as well as overall hypoxia, while endostatin increased total vessel
      spacing, and hypoxia and celecoxib had no marked effects. These results reinforce
      the idea that pathophysiological changes in spontaneous tumors are in general
      reflective of response in transplanted tumors. Furthermore, although DC101
      inhibited growth in roughly half of the spontaneous tumors, the remaining tumors
      were unaffected. A key focus of future studies will be to investigate the
      underlying rationale for the widely varying antiangiogenic response among tumors
      that outwardly appear so similar.

PMID- 16594136
TI  - Non-invasive measurement of tumor oxygenation using embedded microparticulate EPR
      spin probe.
AB  - We have developed a novel procedure for in situ monitoring of oxygen
      concentration in growing tumors by electron paramagnetic resonance (EPR)-based
      oximetry using embedded paramagnetic particulates. The new approach uses spin
      probes that are permanently embedded or implanted in the tumor. A particular
      advantage of this procedure is that it is non-invasive, both in terms of
      implantation of the probe as well as readouts of oxygen. We implanted a mixture
      of RIF-1 tumor cells and microparticulates of lithium phthalocyanine (LiPc) in
      the upper hind leg of C3H mice to grow as solid tumor. This enabled repeated
      measurements of oxygen concentration from the implanted site (tumor) for more
      than two weeks during the progression of the tumor. The particulates that were
      embedded in the tumor were stable and non-toxic to tumor cells. There was no
      apparent inhibitory effect to cell proliferation or tumor growth rate. The
      measurements indicated that the PO2 of the tumor decreased exponentially with
      tumor growth (size) and reached hypoxia (< 4 mm Hg). EPR imaging was used to
      identify the distribution of the particles in the tumor. The data showed a
      heterogeneous distribution of the probe particles within the tumor volume.
      Imaging of oxygen in the growing tumor demonstrated the development of
      significant hypoxia in the tumor within 4-6 days after inoculation. In summary,
      the EPR spectroscopy and imaging using embedded spin probe enabled accurate and
      repeated measurements of PO2 under non-perturbing conditions in growing tumors.

PMID- 16594137
TI  - The effects of tumour blood flow and oxygenation modifiers on subcutaneous
      tumours as determined by NIRS.
AB  - Modulation of tumour oxygenation may be used to increase or decrease tumour
      hypoxia in order to improve the effect of radiotherapy or bioreductive drugs,
      respectively. Magnetic resonance imaging (MRI) and near infrared spectroscopy
      (NIRS) are techniques sensitive to blood deoxyhemoglobin concentration (Hb) that
      can be used to investigate tumour hypoxia indirectly via blood oxygenation
      levels. In this study we have used NIRS to determine absolute Hb and changes in
      deoxyhemoglobin and oxyhemoglobin (HbO) in subcutaneous rodent tumours for
      challenges that alter blood flow and oxygenation, with the aim to better
      interpret our MRI data. Both carbogen [95% O2 + 5% CO2] and 100% O2 breathing
      produced a similar and significant reduction in Hb and increase in HbO, but a
      negligible change in HbT (= Hb + HbO). In contrast, N2 breathing to terminal
      anoxia and intravenous hydralazine produced a negligible increase in Hb, but
      large reductions in HbO and HbT. HbT is proportional to blood volume, so our data
      suggests large blood volume decreases occur with challenges likely to cause
      reduced arterial blood pressure. Hence MRI techniques that measure the R2*
      relaxation rate, which varies linearly with total Hb, will underestimate the
      effects of hypotensive agents at increasing tumour hypoxia.

PMID- 16594138
TI  - Hyperthermia and hypermetabolism in focal cerebral ischemia.
AB  - The reliable and reproducible creation of an animal model of focal cerebral
      ischemia is not easily accomplished. Using a transortibal approach, we showed
      that occlusion of the posterior cerebral artery (PCA), middle cerebral artery
      (MCA), and the contralateral anterior cerebral artery (ACA) created a large
      cortical and subcortical stroke in the non-human primate (NHP). Subsequently, we
      created the same stroke endovascularly in the NHP. Using the endovascular stroke
      model in the NHP, we measured brain temperature with thermocouples and cerebral
      blood flow (CBF) by stable xenon CT in one NHP, and CMRO2 and CBF by positron
      emission tomography (PET) in another NHP. Two female non-human primates (M.
      mulatta) weighing 7.0 and 8.0 kg, respectively, were studied under fentanyl
      diazepam anesthesia with continuous monitoring of arterial blood pressure, rectal
      temperature, and end-tidal CO2 with intermittent blood gas measurements. Using an
      endovascular approach, the PCA (P2), MCA (M1), and the ICA at the bifurcation and
      contralateral ACA produced a large hemispheric stroke. In the right ischemic
      hemisphere, temperatures increased by 2 degrees C-3 degrees C. PET measurement of
      CBF and CMRO2 showed that CMRO2 increased in the region of the ischemic stroke.
      We found that both hyperthermia and hypermetabolism occur in acute stroke.

PMID- 16594139
TI  - Variability of cerebral hemoglobin concentration in very preterm infants during
      the first 6 hours of life.
AB  - Cerebral hemoglobin concentration (cHbc), a major determinant of oxygen transport
      capacity in the brain, shows a considerable variability due to physiological and
      methodological factors. In order to determine the (relative) contribution of
      these factors, the cHbc variability within the first 6 hours of life was studied
      in 28 very preterm infants using near infrared spectrophotometry (NIRS). Mean
      cHbc values were 46.4 +/- 14.1 micromol/l (2.75 +/- 0.84 ml/100 g). Is the
      variability in cHbc related to the methodology of cHbc measurements or to
      physiological variables? A statistical model of stepwise regression (backward
      selection) with 13 independent variables and with cHbc as a dependent variable
      showed that, from the total variability of +/- 14.1 micromol/l, only 3.7
      micromol/l (26%) were of methodological origin, while the major portion, 9.3
      micromol/l (66%) were related to four physiological variables: birth weight,
      gestational age, blood glucose and transcutaneous carbon dioxide tension. The
      remaining 1.1 micromol/l (7.8%) were unexplained. We conclude that NIRS, which
      allows continuous monitoring of cerebral oxygenation and metabolism even in the
      first hours of postnatal life, is a valid technique to measure cHbc in very
      preterm infants. The major portion of the large variability of early cHbc
      registrations can be attributed to physiological factors.

PMID- 16594140
TI  - Computational study on use of single-point analysis method for quantitating local
      cerebral blood flow in mice.
AB  - The benefits of a mouse model are efficiency and availability of transgenics/
      knockouts. Quantitation of cerebral blood in small animals is difficult because
      the cannulation procedure may introduce errors. The [14C]-iodoantipyrine
      autoradiography (IAP) method requires both the tissue concentration and the time
      course of arterial concentration of the [14C] radioactive tracer. A single point
      analysis technique was evaluated for measuring blood flow in mice (30 g +/- 0.3
      g; n = 11) by using computational models of sensitivity analysis, which
      quantitates relationships between the predictions of a model and its parameters.
      Using [14C]-IAP in conjunction with mathematical algorithms and assumed arterial
      concentration-versus-time profiles, cortical blood flow was deduced from single
      point measurements of the arterial tracer concentration. The data showed the
      arterial concentration profile that produced the most realistic blood flows (1.6
      +/- 0.4; mean +/- SD, ml/g/min) was a profile with a ramp time of 30 sec followed
      by a constant value over the remaining time period of 30 sec. Sensitivity
      analysis showed that the total experimental time period was a more important
      parameter than the lag period and the ramp period. Thus, it appears that the
      accuracy of the assumption of linearly increasing arterial concentration depends
      on the experimental time period and the final arterial [14C]-iodoantipyrine
      concentration.

PMID- 16594141
TI  - Effects of temperature on oxygen transport in sheets and spheres of respiring
      tissues.
AB  - The effect of temperature upon the oxygen partial pressure profiles (and hence
      upon flux) of oxygen through respiring tissues of differing architecture is
      examined. We have considered the two situations of respiring sheets of tissue and
      of respiring spheres. Sheets of respiring tissue can model to some extent the
      behaviour of skin (which abandons its own temperature stasis in response to its
      obligations in the control of overall body temperature). The oxygen profiles of
      spheres of respiring tissues subject to temperature shifts is investigated since
      it is a model for solid tumour oxygen kinetics where a spherical tumour,
      inadequately supplied with a capillary network, is being treated by one or
      another form of hyperthermia during cancer therapy.

PMID- 16594142
TI  - Modeling of the response of ptO2 in rat brain to changes in physiological
      parameters.
AB  - It is known that oxygen tension in tissue (ptO2) will change in response to an
      alteration of physiological parameters including: pCO2 in arterial blood, blood
      flow, capillary density, oxygen carrying capacity, and p50 of hemoglobin. We have
      used modeling to compute the change of PtO2 in response to changes of each
      physiological parameter and related these changes to experimental data. The
      oxygen distribution in a Krogh cylinder was computed assuming a linear decrease
      of hemoglobin saturation from the arterial to the venous end of the capillary.
      Parameters of the model were used to compute the baseline cerebral PtO2 expressed
      as the mean value of the PtO2 over the whole cylinder. These parameters were
      adjusted to derive PtO2 values close to those measured at the relevant
      experimental conditions. Then each desired parameter was varied to calculate the
      change in PtO2 related to this parameter. Effects of different factors on
      cerebral PtO2 were modeled and compared with experimental values obtained with
      various experimental interventions including: changing CBF, modifying p50 with
      the allosteric modifier RSR13, modification of capillary density, and hemoglobin
      content. An acceptable agreement of the computed and the experimental changes of
      the cerebral PtO2 was obtained for these experimental conditions.

PMID- 16594143
TI  - Black magic and EPR oximetry: from lab to initial clinical trials.
AB  - EPR oximetry is a technique that can make repeated non-invasive measurements of
      the PO2 in tissues. To extend the application of EPR oximetry to humans, India
      ink is the probe of choice because appropriate India inks have EPR signals whose
      line widths are sensitive to changes in oxygen concentrations, and, most
      importantly, India ink already has been used extensively in humans as a marker in
      the skin, lymphatics, various organs during surgery, tumors, and for decoration
      as tattoos. We have developed an India ink that has good sensitivity to oxygen,
      high stability in tissues, good signal intensity, and minimal toxicity. In this
      article we describe the various properties of this India ink, results obtained
      from our animal experiments, and our first preliminary clinical results, which
      are part of the first systematic clinical use of EPR oximetry. The clinical
      results indicate that it is possible to do repeated measurements over several
      months and probably years after the injection of the ink, indicating that long
      term follow-up studies are feasible. We are very encouraged with these results
      and are confident that EPR oximetry using India ink will be a non-invasive, fast,
      and reliable technique for pO2 measurements in clinical studies.

PMID- 16594145
TI  - Differentiating hemodynamic compromise by the OEF response to acetazolamide in
      occlusive vascular disease.
AB  - Identification of increased stroke risk in a population of symptomatic patients
      with occlusive vascular disease (OVD) is presently accomplished by measurement of
      oxygen extraction fraction (OEF) or cerebrovascular reserve (CVR). However, many
      regions identified by compromised CVR are not identified by OEF. Our aim was to
      determine whether the response of OEF to acetazolamide, namely, oxygen extraction
      fraction response (OEFR) would identify those hemispheres in hemodynamic
      compromise with normal OEF. Nine patients symptomatic with transient ischemic
      attacks and strokes, and with occlusive vascular disease were studied. Anatomical
      MRI scans and T2-weighted images were used to identify and grade subcortical
      white matter infarcts. PET cerebral blood flow (CBF) and OEF were measured after
      acetazolamide. The relationship between CVR and oxygen extraction fraction
      response (OEFR) showed that positive OEFR occurred after acetazolamide despite
      normal baseline OEF values. The two hemispheres with positive OEFR were also
      associated with severe (> 3 cm) subcortical white matter infarcts. We found that
      the OEFR was highly correlated with CVR and identified hemispheres that were
      hemodynamically compromised despite normal baseline OEF.

PMID- 16594144
TI  - Axial oxygen diffusion in the Krogh model: modifications to account for
      myocardial oxygen tension in isolated perfused rat hearts measured by EPR
      oximetry.
AB  - The cylindrical steady-state model developed by Krogh with Erlang has served as
      the basis of understanding oxygen supply in living tissue for over eighty years.
      Due to its simplicity and agreement with some observations, it has been
      extensively used and successfully extended to new fields, especially for
      situations such as drug diffusion, water transport, and ice formation in tissues.
      However, the applicability of the model to make even a qualitative prediction of
      the oxygen level of specific volumes of the tissue is still controversial. We
      recently have developed an approximate analytical solution of a steady-state
      diffusion equation for a Krogh cylinder, including oxygen concentration in the
      capillary. This model was used to explain our previous experimental data on
      myocardial pO2 in isolated perfused rat hearts measured by EPR oximetry. An
      acceptable agreement with the experimental data was obtained by assuming that a
      known limitation of the existing EPR methods--a tendency to over-weight low pO2
      values--had resulted in an under-estimate of the pO2. These results are
      consistent with recent results of others, which stress the importance of taking
      into account the details of what is measured by various methods.

PMID- 16594146
TI  - The anomalous Einstein-Stokes behaviour of oxygen and other low molecular weight
      diffusants.
AB  - Almost a century ago, Einstein and Sutherland independently derived equations
      that describe the relationship between diffusion of solutes and the molecular
      parameters of those solutes. In that time it has been recognized that, although
      the equations adequately describe the diffusion of large and medium-sized
      molecules, there is deviation from this relationship for small molecules. Many
      authors have attempted to redefine the equations for diffusion, with varying
      degrees of success, but generally have not attempted to consider the fundamental
      events that may be occurring at the molecular level during the diffusion of small
      molecules. In this presentation, we attempt to provide such an explanation,
      particularly with respect to the diffusion of oxygen through water. We consider
      the possibility of a random rotational model that complements the (slower)
      translational process of traditional diffusion and thereby provides accelerated
      diffusion of small molecules. It is hoped that our description of this model may
      provide a basis for the development of mathematical modelling of the process.

PMID- 16594147
TI  - Gut dysoxia: comparison of sites to detect regional gut dysoxia.
AB  - Dysoxia, a state in which O2 supply is inadequate to meet tissue metabolic needs,
      is often first detected in regional organs such as the gut. An increase in PCO2
      is believed to reflect the development of gut dysoxia. The stomach is a well
      documented clinical site for detecting gut PCO2; however, measurement issues make
      this a less than ideal monitoring site. Other sites along the GI tract may be
      equally sensitive to detect changes in PCO2. Rectal CO2 measurement may have the
      advantage of being less invasive, low risk, and continuous without the
      limitations associated with gastric monitoring. In this study, we compared PCO2
      at two sites (gastric, rectum) at baseline and during a dysoxic challenge,
      cardiac arrest. We obtained similar values of PCO2 at both sites. Ten male Wistar
      rats were anesthetized with 1%-2% Isoflurane/50% nitrous oxide/balanced O2 and
      the tail artery and right atrium were cannulated. Severinghaus-type active tip
      PCO2 electrodes (Microelectrode Inc, Bedford, NH) were calibrated and one
      electrode was surgically inserted into the stomach (G-PCO2) and a second
      electrode was placed in the rectum (R-PCO2). Animals were stabilized following
      surgery. Cardiac arrest was induced by administering a rapid injection of
      norcuron (0.1-0.2 mg/kg) and potassium chloride solution (0.5 M/L; 0.12 mL/100 gm
      of body weight). Animals were monitored for 15 minutes post-arrest. Data were
      collected at one minute intervals using the software Data Collect. All data are
      reported as mean +/- SD. Baseline G-PCO2 was 64 +/- 17 torr, not significantly
      different from R-PCO2, 58 +/- 7 torr. After 15 minutes of cardiac arrest, G-PCO2
      rose to 114 +/- 42 torr, again not significantly different from R-PCO2, which
      reached 112 +/- 35 torr. Monitoring PCO2 in the rectum is less invasive and might
      provide similar information when compared with gastric monitoring at baseline and
      during a dysoxic challenge.

PMID- 16594148
TI  - Imaging oxygen pressure in the retina of the mouse eye.
AB  - The phosphorescence lifetime imaging system previously used to image oxygen in
      the retina of the cat eye was modified to allow imaging of phosphorescence
      lifetimes in the much smaller mouse eye. Following the lead of Shonat and
      coworkers, a frequency domain approach was used in which the excitation light
      source was modulated in a 50% on: 50% off square wave while the gate of the
      intensified CCD camera was similarly modulated but delayed with respect to the
      excitation. These were analyzed by fitting the intensity at each pixel to a
      sinusoid. The phase of the phosphorescence relative to the excitation was
      determined and from the phase shift and frequency, the phosphorescence lifetime
      was calculated. The Stern-Volmer relationship was then used to calculate the
      oxygen pressure at each pixel of the image array. High resolution maps of
      phosphorescence lifetime and oxygen pressure in the retina of the mouse eye have
      been attained. The retinal veins draining into the optic head appear as large,
      highly phosphorescent vessels against a lower phosphorescence background with a
      network of smaller vessels. The oxygen pressure in the retinal veins is typically
      from 20 to 30 mm Hg while the background has somewhat higher oxygen pressures.
      Experiments are underway to resolve the oxygen in the choroid from that in the
      retina. The arteries on the retinal surface can be observed, but their small
      diameter, relatively high oxygen pressures (> 90 mm Hg), and surrounding tissue
      with much lower oxygen pressures, makes accurate determination of the oxygen
      pressure a challenge.

PMID- 16594149
TI  - Fluorescence-mediated detection of a heterogeneity in a highly scattering media.
AB  - Tumors usually become localized absorbers at near infrared (NIR) wavelengths due
      to the increase in hemoglobin amount around the tumor, which is caused by
      angiogenesis. When a tumor is small and/or deeply seated, the contrast by the
      hemoglobin only, however, may not be strong. For such situation, contrast agents
      may be helpful, because they are preferentially accumulated in the tumor due to
      the unorganized tumor vasculature. In this study, indocyanine green (ICG) was
      used as a contrast enhancer. ICG is safe, absorbs NIR, and also generates
      fluorescence. A breast tissue-like model, embedded with a tumor model (1.2 x 0.7
      x 0.5 cm) with/without ICG at a 1 cm depth, was constructed and the surface was
      scanned by a NIR time-resolved spectroscopy instrument. Enhanced contrast by ICG
      was confirmed in both absorption and fluorescence. For absorption, transmittance
      contrast was approximately two times higher than reflectance. In reflectance, the
      contrast by fluorescence was approximately four times higher than absorption.
      This study result shows that the information on both the absorption and
      fluorescence by ICG can be effectively used in detecting a tumor. A study of the
      ICG effect on deeper absorber detection is in progress.

PMID- 16594150
TI  - Developing strategies for three-dimensional imaging of oxygen tension in the
      rodent retina.
AB  - Insufficient oxygen delivery and retinal hypoxia have been implicated as causal
      in the development of many devastating diseases of the eye. While the two
      dimensional imaging of retinal oxygen tension (PO2) has now been applied in a
      variety of different animal models, it is fundamentally a luminescence-based
      system lacking depth discrimination. However, mammalian retinal tissue is
      nourished by two distinct vascular beds, the retinal and the choroidal
      vasculatures, and they are exceedingly difficult to separate using traditional
      two-dimensional imaging strategies. Numerous studies have demonstrated that
      retinal and choroidal PO2 differ substantially. Therefore, the single PO2 value
      currently returned through data analysis cannot accurately represent the separate
      contributions of the choroidal and retinal vasculatures to the state of retinal
      oxygenation. Such a separation would significantly advance our understanding of
      oxygen delivery dynamics in these two very distinct vasculatures. In this study,
      we investigate new strategies for generating separate retinal and choroidal PO2
      maps in the rodent retina using our existing phosphorescence-based lifetime
      imaging system.

PMID- 16594151
TI  - Cerebral PtO2, acute hypoxia, and volatile anesthetics in the rat brain.
AB  - We describe our results on the effect in rats of two commonly used, volatile
      anesthetics on cerebral tissue PO2 (PtO2) and other physiological parameters at
      FiO2 levels ranging from 0.35 to 0.1. The study was performed in 12 rats that had
      lithium phthalocyanine (LiPc) crystals implanted in the left cerebral cortex.
      FiO2 was maintained at 0.35 during surgical manipulation and baseline EPR
      measurements, after which time, each animal was exposed to varying levels of FiO2
      (0.26, 0.21, 0.15, and 0.10) for 30 minutes at each level. No significant
      difference in PtO2 was observed between the isoflurane and halothane groups at
      any FiO2 level, and the cerebral arterial PO2 (PaO2) also was similar for both
      groups. However, the cerebral PtO2 under both isoflurane and halothane anesthesia
      was lower during hypoxia (FiO2 < or = 0.15) than under normoxia (FiO2 = 0.21) and
      there was a significant difference in mean arterial blood pressure (MABP) between
      isoflurane and halothane groups under both mild and severe hypoxia. The pH and
      cerebral arterial PCO2 (PaCO2) were similar for the halothane and isoflurane
      groups during normoxia (FiO2 = 0.21) and mild hypoxia (FiO2 = 0,15), but
      following severe hypoxia (FiO2 = 0.10), both parameters were lower in the
      halothane anesthetized animals. These results confirm that cerebral PO2 cannot be
      inferred directly from measurements of other parameters, indicating that
      methodology incorporating continuous direct measurement of brain oxygen will lead
      to a better understanding of cerebral oxygenation under anesthesia and hypoxia.

PMID- 16594152
TI  - Rate of change in cerebral oxygenation and blood pressure in response to passive
      changes in posture: a comparison between pure autonomic failure patients and
      controls.
AB  - The cardiovascular and cerebrovascular responses to head-up postural change are
      compromised in pure autonomic failure (PAF) patients because of sympathetic
      denervation. The aim of this study was to characterize the rate of change of
      systemic mean blood pressure (MBP) and cerebral haemodynamics in response to
      passive posture changes. Nine PAF patients and 9 age-matched controls took part
      in this study. MBP and oxy- (O2Hb), deoxy-haemoglobin (HHb), and tissue
      oxygenation index (TOI) on the forehead were continuously monitored non
      invasively using the Portapres and near-infrared spectroscopy (NIRS),
      respectively. From visual inspection of the haemoglobin difference signal
      (Hb(diff) = O2Hb-HHb), seven distinct phases were marked (1: supine, 2: start
      passive tilt, 3: head up to 60 degrees degrees, 4: end of tilt, 5: tilt reversal,
      6: return to supine, 7: rest); the same time points were used for all of the
      other signals. For each phase, the slope was calculated using a linear regression
      algorithm. Significant differences were found between PAF patients and controls
      in the Hb(diff) slope magnitudes for phases 3 (P < .05) and 5 (P = .01), and the
      duration of phase 2 (P < .05). MBP slope magnitudes showed significant
      differences for phases 2 (P < .01) and 5 (P < .01). These differences in the rate
      of change suggest differences in blood vessel resistance related to sympathetic
      activation.

PMID- 16594153
TI  - Validation of the CAS neonatal NIRS system by monitoring vv-ECMO patients:
      preliminary results.
AB  - The CAS neonatal NIRS system determines absolute regional brain tissue oxygen
      saturation (SnO2) and brain true venous oxygen saturation (SnvO2) non-invasively.
      Since NIRS-interrogated tissue contains both arterial and venous blood from
      arterioles, venules, and capillaries, SnO2 is a mixed oxygen saturation
      parameter, having values between arterial oxygen saturation (SaO2) and cerebral
      venous oxygen saturation (SvO2). To determine a reference for SnO2, the relative
      contribution of SvO2 to SaO2 drawn from a brain venous site vs. systemic SaO2 is
      approximately 70:30 (SvO2:SaO2). If the relationship of the relative average
      contribution of SvO2 and SaO2 is known and does not change to a large degree,
      then NIRS true venous oxygen saturation, SnvO2, can be determined non-invasively
      using SnO2 along with SaO2 from a pulse oximeter.

PMID- 16594154
TI  - Interactions between HIF-1 and Jab1: balancing apoptosis and adaptation. Outline
      of a working hypothesis.
AB  - When cells experience hypoxia, they either die by apoptosis or adapt to the
      hypoxic conditions by a series of compensatory mechanisms. Hypoxia inducible
      factor-1 (HIF-1) is a transcription factor involved in both processes, but the
      exact mechanisms regulating whether the cells survive (adapt) or perish by
      apoptosis are largely unknown. We hypothesize that the balancing between
      apoptosis and adaptation is governed by a triangular feedback system involving
      the alpha-subunit of HIF-1, p53, and jun activating binding protein 1 (Jab1).
      Jab1 and p53 bind competitively to the same domain on HIF-1alpha resulting in
      either stabilization or degradation of HIF-1alpha, respectively. Moreover, p53 is
      stabilized by binding to HIF-1alpha, whereas its interaction with Jab1 targets
      p53 for degradation. Thus as a consequence we propose that the ratio between p53
      and Jab1 determine whether a hypoxic induction of HIF-1 results in apoptosis or
      adaptation, with Jab1 as the factor promoting adaptation. On this background we
      consider Jab1 an interesting molecular target for anticancer therapy.

PMID- 16594155
TI  - Past, present, and future of oxygen in cancer research.
AB  - The first pathologists, oncologists, and medical physicists were aware that
      tumors were populated by an aberrant vasculature. The classic observations of
      Thomlinson and Gray in the 1950's established that O2 diffusion distances caused
      tumor to grow in cords. Tumor necrosis was observed surrounding a Krogh cylinder
      of viable tumor. That work helped explain earlier work by Warburg, who
      demonstrated a predisposition for tumors to favor anaerobic respiration, and it
      became the basis for 5 decades of subsequent research aimed at improving tumor
      oxygenation at the time of radiation. The role of O2 in modifying radiation
      response was attributed exclusively to the reactive free radicals that can be
      formed when O2 is present. These radicals produce approximately three-fold more
      irreparable double strand breaks in DNA. Subsequently it became clear that tumor
      had nutritional insufficiencies in addition to hypoxia. Ischemic regions are
      hypoglycemic, acidotic, have poor penetration of drugs, increased interstitial
      pressure, and altered immunological states. Ischemic regions can have
      intermittent reflow and associated redox stress. The relative impact of O2
      compared to these associated phenomenon, and the degree to which hypoxia causes
      or follows these associated physiologic stresses, have been studied in detail.
      ISOTT scientists are responsible for much of the elucidation of the specific
      effects of O2, ADP/ATP ratios, hypoglycemia, and acidosis on tumor responses to
      radiation and hyperthermia. Many questions still remain.

PMID- 16594156
TI  - Benzoate hydroxylation: a measure of oxidative stress in divers.
AB  - Hyperoxia may facilitate the formation of reactive oxygen species. Recent
      experiments indicated signs of oxidative stress after 3.5 h hyperoxic diving. We
      analyzed in the urine of healthy, 100% O2-breathing male volunteers before and
      after 45 min seawater diving (170 kPa) or 30 min resting at 280 kPa in a pressure
      chamber (HBO) for sub-fractions of hydroxybenzoate (HB), monohydroxybenzoate
      (MHB), and of dihydroxybenzoate (DHB). Measurements were performed by HPLC and
      electrochemical or UV-detection. Additionally, urinary concentrations of
      thiobarbituric acid-reactive substances (TBARS) and of creatinine (CREA) were
      analyzed by standard colorimetric assays. During HBO treatment, TBARS, DHB, 2,4
      DHB, and 3,4-DHB increased significantly. MHB and CREA did not change. 2,4- and
      3,4-DHB-alterations correlated with changes in TBARS. Diving induced urine
      dilution and stimulated oxygen consumption. Urinary TBARS and HB rose
      significantly higher during diving at 170 kPa than during HBO at 280 kPa. A
      different pattern in urinary sub-fractions of DHB could be observed in divers:
      2,6 > 2,3 > 2,5 > 3,4. Changes in 2,6- and 2,5-DHB correlated significantly with
      alterations in TBARS. 2,6-DHB probably indicated renal oxidant stress similar to
      previously described animal experiments. It is concluded that analyzing urinary
      HB may provide a sensitive measure to quantify and qualify oxidant stress in
      divers.

PMID- 16594157
TI  - Mitochondrial NADH as the bellwether of tissue O2 delivery.
AB  - It is proposed that the redox state of mitochondrial NADH will complement blood
      gas analysis for measuring the health and welfare of human tissues. Use of
      arterial oxygen saturation levels (SaO2), especially as assayed by the Nellcor
      instrument, has spread almost everywhere in medicine despite the fact that
      hypoxia of internal organs, liver, kidney, brain, pancreas, etc. is not well
      indicated by peripheral digital oxygenation. Indeed, there is an implied
      liability in the failure to infer central oxygenation from peripheral values.
      Near infrared (NIR) sensing of deep tissue saturation of hemoglobin (StO2)
      requires multi-wavelength, multi-site measurement of both absorption and
      scattering properties by time or frequency domain NIR methods. Corrections for
      underlying water and lipid absorptions can be made so that the correct value for,
      and saturation oh hemoglobin are obtained. Nevertheless, the significance of
      blood oxygen saturation, even localized to particular organs, can be questioned
      from the standpoint of what is the critical value of the desaturation from which
      the tissue can recover; for example, in the case of cortical neurons where
      stroke, compression ischemia, etc. cause O2 lack, this value becomes of
      significant clinical importance in both the brain and the spinal chord. These
      approaches are actively pursued and the possibility of subsurface redox state
      measurement in human tissues may eventually emerge as the quantitative metric of
      tissue metabolic state and of hypoxic stress. The great flexibility and
      versatility of the fast, economical and "tetherless" nature of opto-electronic
      technology is appropriate to the manifold challenges of neuronal function as
      currently measured by intrinsic signals and soon to be studiable by extrinsic
      signals of metabolism and electrophysiological functions.

PMID- 16594158
TI  - Process scale-up studies for protein C separation using IMAC.
AB  - Protein C (PC) is the pivotal anticoagulant and antithrombotic in the human
      coagulation cascade. PC deficiency can disturb the blood hemostasis and cause
      thrombosis, inhibiting oxygen transport to tissue, and resulting in major medical
      problems such as deep vein thrombosis (DVT). The current treatment can cause
      bleeding and other major medical problems. PC circulates in the blood as a
      zymogen and is only activated when and where it is needed. PC is a safe
      anticoagulant without harmful side effects. A combination of ion-exchange
      chromatography and IMAC IDA-Cu was studied for the relatively large scaled PC
      separation from Cohn fraction IV-1. Almost half of the active PC was recovered by
      using this process. In future work, we will verify the linearity of the IMAC
      column scale-up. This process can be used to produce PC from Cohn fraction IV-1
      at large quantities and low cost to treat PC-deficient patients.

PMID- 16594160
TI  - Rate of decrease of PO2 from an arteriole with arrested flow.
AB  - When flow to a region is arrested, the amount of oxygen contained within the
      stationary blood decreases at a rate dependent on the oxygen utilization of the
      surrounding tissue. We used phosphorescence quenching microscopy to measure
      arteriolar PO2 in the mesentery of male Sprague-Dawley rats. Flow was quickly
      stopped (< 1 s) by occluding the microvessels using an inflatable Saran bag
      attached to the microscope objective. The rate of decline in PO2 following
      occlusion yielded a calculated initial flux of oxygen out of the vessel lumen of
      8.0 x 10(-7) ml O2 cm(-2) sec(-1). An upper limit on the oxygen consumption of
      the arteriolar wall was calculated by assuming that all of the oxygen in the
      lumen was consumed by the wall at the initial rate. This value was 2.5 x 10(-3)
      ml O2 cm(-3) sec(-1) and is an overestimate since the oxygen consumption of the
      nearby parenchymal cells was neglected. The calculated maximum oxygen consumption
      of the wall is more than an order of magnitude smaller than that reported
      previously for arterioles in the rat mesentery (6.5 x 10(-2) ml O2 cm(-3) sec(
      1)). We conclude that oxygen consumption of the arteriolar wall is similar to
      previous values for other vascular tissues.

PMID- 16594159
TI  - Hypoxia-induced alterations in hyaluronan and hyaluronidase.
AB  - Hyaluronan (HA), a large negatively-charged polysaccharide, is a major component
      of vessel basal membrane. HA is expressed by a variety of cells, including tumor
      and endothelial cells. We hypothesized that HA could be up-regulated by hypoxia
      to enhance vessel formation. To determine the effect of hypoxia on the production
      of HA, tumor cells were treated with either media alone (control) or a hypoxia
      inducer (CoCl or NaN3) for 24 h. The level of HA in the media was then measured
      by ELISA. The results showed that both CoCl and NaN3 induced the production of
      HA. Since the low molecular weight form of HA (SMW) possesses pro-angiogenic
      properties, we investigated whether hypoxia-induced HA can be processed into SMW.
      Under hypoxic conditions, the activity of hyaluronidase, the enzyme responsible
      for degrading HA, was measured by an ELISA-like assay. The activity of
      hyaluronidase was shown to be up-regulated by hypoxia and, further, could carry
      out the function of processing HA into SMW. In addition, the hypoxic areas of
      tumor tissues were stained strongly with biotinylated HA-binding proteins,
      indicating that the level of HA was high compared to the oxic areas. This study
      demonstrates that hypoxia can stimulate the production of HA and the activity of
      hyaluronidase, which may promote angiogenesis as a compensation mechanism for
      hypoxia.

PMID- 16594161
TI  - Measurement of CMRO2 in neonates undergoing intensive care using near infrared
      spectroscopy.
AB  - Greater understanding of the rate of oxygen delivery and uptake in sick preterm
      and term infants undergoing intensive care is an important aim of brain
      orientated neonatal medicine. Near infrared spectroscopy (NIRS) is a continuous,
      non-invasive and portable technique which can be used to measure cerebral blood
      flow (CBF) in infants. It is also possible to use spatially resolved spectroscopy
      to measure absolute mean cerebral oxygen saturation (SmcO2). The aim of this
      study was to investigate the derivation of cerebral metabolic rate for oxygen
      (CMRO2) from these two measurements. Nine preterm infants were studied, of median
      (range) gestational age 25 (23-37) weeks. A NIRO300 was used to measure CBF and
      SmcO2 simultaneously over the right and left hemisphere. Median (range) left and
      right cerebral hemisphere values for CMRO2 were 0.95 (0.79-1.53) ml 100g(-1) x
      min(-1) and 0.88 (0.69-1.46) ml 100g(-1) x min(-1), respectively. No significant
      difference was seen between the left- and right-sided values. These values are
      similar to median (range) values previously reported in infants using positron
      emission tomography or more invasive NIRS methods. Further work is necessary to
      define limits on the use of this technique, particularly in the assumption of the
      venous:arterial compartment volume ratio across different infants.

PMID- 16594162
TI  - The pathways of oxygen in brain. I. Delivery and metabolism of oxygen.
AB  - Flow-metabolism coupling in brain is different from flow-metabolism coupling in
      other vascular beds. In the classic description of Krogh, the capillary bed is a
      system of parallel tubes serving cylinders of tissue known as Krogh's cylinders.
      This simple arrangement yielded a quantitative expression of oxygen delivery to
      the tissue. However, in brain tissue, the arrangement is so disorderly that no
      prediction of oxygen tensions in the tissue is possible. Only two claims of the
      capillary bed in the brain appear to be indisputable, i.e., the capillaries have
      a common arterial source and a common venous terminus, and their density is
      proportional to the average regional rates of metabolism at steady-state. The
      following revision of the mechanism of flow-metabolism coupling in brain arose
      from the simple assumption, first introduced by Erwin R. Weibel in The Pathway
      for Oxygen, that every segment of the capillary bed "feeds" the same amount of
      brain tissue, i.e., that every fraction of the tissue is served by commensurate
      fractions of capillary density and oxygen diffusibility and accounts for the same
      fraction of the total oxygen consumption.

PMID- 16594163
TI  - The pathways of oxygen in brain. II. Competitions for cytochrome c oxidase and
      NOS are keys to flow-metabolism coupling.
AB  - It has been well-known for many years that cerebral oxygen consumption remains
      constant during moderate changes of blood flow, as measured during hypo- or
      hypercapnia or indomethacin administration. Current models of flow-metabolism
      coupling link blood-brain transfer of oxygen to oxygen metabolism in
      mitochondria. The resulting quantitative relations between flow and metabolism
      reveal that a close link between diffusion and metabolism prevents the enzyme
      from maintaining a constant oxygen consumption when blood flow changes, unless
      the enzyme's affinity towards oxygen is adjusted commensurately.

PMID- 16594165
TI  - The difficulties in comparing in vivo oxygen measurements: turning the problems
      into virtues.
AB  - There has been rapid development of effective new tools that provide information
      on oxygenation in vivo and an increased recognition of how valuable such
      information can be. Consequently, there also has been considerable interest in
      comparing and evaluating the accuracy and usefulness of the different types of
      measurements. The various types of measurements usually do not measure the same
      thing. They may measure PO2 or [O2] or something less directly related, such as
      hemoglobin saturation. They may make measurements in different compartments (e.g.
      intracellular, extracellular, vascular) in the volume that they sample, the time
      span over which they average, the local perturbation that they may cause, etc.
      They also differ in their sensitivity, accuracy, ability to measure repetitively.
      However, these potentially confounding and confusing differences can be made into
      an outstanding virtue, if their nature is considered carefully. Then a proper
      model can relate them to each other. The ability to relate the various
      measurements to each other can be a powerful tool to test the validity of models
      that attempt to explain fully the distribution of oxygen in real systems and the
      factors that affect this. We then could have a major advancement in our
      understanding of oxygen transport in tissues, with an ability to determine
      accurately the effects of physiological and pathophysiological perturbations on
      oxygenation at all levels of cells and tissues in vivo.

PMID- 16594164
TI  - Exogenous and endogenous markers of tumour oxygenation status: definitive markers
      of tumour hypoxia?
AB  - Hypoxia is a physiological abnormality that has been detected in all solid
      tumours analysed to date. Studies using polarographic needle electrodes have
      shown an unequivocal link between the extent of tumour hypoxia and poor treatment
      outcome. The practical limitations of polarographic needle electrodes have
      warranted investigation into alternative strategies enabling routine assessment
      of tumour hypoxia in the clinical setting. This review focuses on the clinical
      evaluation of exogenous and endogenous markers of tumour hypoxia that may fulfil
      this role.

PMID- 16594166
TI  - Preliminary study of simultaneous multi-anticoagulant deficiency diagnosis by
      fiber optic multi-analyte biosensor.
AB  - Protein C (PC), protein S (PS), antithrombin III, and plasminogen are four
      important anticoagulants in blood plasma. Deficiency of any of these biomolecules
      may lead to thrombo-embolic complications including lung embolism, heart attack,
      and stroke. A multi-factor sensing system is beneficial for identifying the cause
      of abnormal blood clotting more effectively, rapidly, and cost-effectively. As an
      initial effort toward simultaneous multi-anticoagulant detection, a PC and PS
      dual-sensing system has been under development in our research group. A
      fiberoptic PC biosensor utilizing fluorophore-mediated sandwich immunoassay was
      already developed for rapid (-5 minutes) PC deficiency diagnosis. After a single
      PS sensor was developed for the PS deficiency diagnosis, the two sensors were
      connected in series to form a dual-sensing system. The cross-reactivity between
      the analytes and the sensors was found to be minimal. For easier sensing
      operation, a mixture of fluorophore-linked anti-PC and anti-PS was applied. The
      results showed that the mixture can be used with a slight signal reduction. When
      PC and PS was mixed in a sample, the signal intensity was decreased by
      approximately 5% for both sensors. A study is currently being performed to
      overcome the signal reduction by increasing the flow velocity and incubation
      time.

PMID- 16594167
TI  - Circulation time in man from lung to periphery as an indirect index of cardiac
      output.
AB  - Circulation time (Ct) between lung and periphery may be a surrogate for cardiac
      output, estimated here, for the most part, as the time between taking a breath of
      nitrogen and peripheral detection of a desaturation pulse. Use of pulse oximetry
      involves an internal, instrument delay; however, using the ear, we found
      shortening with exercise (12.1 +/- 0.37 sec, at rest; 9.1 +/- 0.25 sec at 100
      watts), lengthening after beta-blockade, and lengthening in patients with
      echocardiographic and clinical left heart failure (8 patients 16.2 +/- 1.1 sec; 6
      controls 12.0 +/- 0.5 sec). Pulse oximetry failed, however, to discriminate heart
      failure from normal in several patients. In patients referred to a department of
      nuclear medicine for assessment of chest pain, pulse oximetry (finger and ear)
      showed unacceptable variability. Nuclide delays between lung and carotid artery
      correlated significantly with the reciprocal of gated SPECT estimated cardiac
      output (Q(gs)); not so, however, for lung to finger. In normal subjects, an old
      Waters fast response oximeter gave short, reproducible Ct estimates and a
      significant correlation with the reciprocal of (indirect Fick) cardiac output
      (Q(if)). The relationship for normal subjects was: Ct = 0.28 x 60/Q(if) + 2.8 sec
      (Q(if) in L min.; P slope < .001).

PMID- 16594168
TI  - Factors controlling oxygen utilization.
AB  - We demonstrate, theoretically, that oxygen diffusion distance is related to the
      metabolic rate of tumors (QO2) as well as the oxygen tension. The difference in
      QO2 rate between tumors can vary by as much as 80-fold. Inhibition of oxygen
      utilization by glucose or chemical inhibitors can improve the diffusion distance.
      Combining respiratory inhibitors with increased availability of oxygen will
      further improve the oxygen diffusion distance for all tumors. A simple means for
      inhibiting oxygen consumption is the use of glucose (the Crabtree effect). The
      inhibition of tumor oxygen utilization by glucose occurs in R323OAc mammary
      carcinoma and 9L glioma cells. However, stimulation of oxygen consumption is
      observed with glucose in the Q7 hepatoma cell line. MIBG, a known inhibitor of
      oxygen utilization, blocks oxygen consumption in 9L, but is weakly inhibitory
      with the Q7. Q7 tumor cells demonstrate an anomalous behavior of glucose and MIBG
      on oxygen consumption. Our results clearly demonstrate the necessity for
      comparing effects of different agents on different tumor cells. Generalizations
      cannot be made with respect to the choice of inhibitor for in vivo use. Our work
      shows that oxygen consumption also can be inhibited with malonate and
      chlorosuccinate. These substrates may be effective in vivo, where glucose is low
      and glutamine is the major substrate. Our results indicate that information about
      individual tumor substrate-linked metabolic controls may be necessary before
      attempting to inhibit oxygen utilization in vivo for therapeutic benefit.

PMID- 16594169
TI  - Amputation level viability in critical limb ischaemia: setting new standards.
AB  - We have previously demonstrated the successful use of skin oxygen saturation
      (SO2) measurements to predict the healing viability in lower limb amputations for
      critical limb ischaemia. The measurements are quick and easy to perform, but the
      instrument that has been used to date is now obsolete and a new, lightweight,
      portable instrument has recently been introduced. However, fundamental
      differences between the two instruments could influence the criteria used for
      determining amputation level viability. The purpose of this study was to compare
      the in vivo measurements using the two instruments in order to validate
      amputation level viability criteria using the RM200. Skin SO2 measurements were
      carried out on critically ischaemic lower limbs of patients, and on the forearms
      of normal volunteers during before, during and after a 5 minute period of
      tourniquet ischaemia. A linear correlation (r2 = 0.91) was found between the
      values obtained from the two instruments within the range of interest (0 to 40%
      SO2). Differences between the instruments lay within 1 standard deviation of the
      mean, demonstrating a high degree of agreement between the two methods. The RM200
      is thus an acceptable replacement for the MCPD instrument for amputation level
      viability assessments.

PMID- 16594170
TI  - Hypoxia in breast cancer: role of blood flow, oxygen diffusion distances, and
      anemia in the development of oxygen depletion.
AB  - Heterogeneously distributed hypoxic areas are a characteristic property of
      locally advanced breast cancers. Hypoxia results from an imbalance between the
      supply and consumption of oxygen (O2). Major pathogenetic mechanisms for the
      emergence of hypoxia are (i) structural and functional abnormalities in the tumor
      microvasculature, (ii) an adverse diffusion geometry, and (iii) tumor-related and
      therapy-induced anemia leading to a reduced O2 transport capacity of the blood.
      There is pronounced intertumor variability in the extent of hypoxia, which is
      independent of clinical size, stage, histology and grade. Hypoxia is intensified
      in anemic patients, especially in tumor (areas) with low perfusion rates. Tumor
      hypoxia is a therapeutic problem since it makes solid tumors resistant to
      sparsely ionizing radiation, some forms of chemotherapy, and photodynamic
      therapy. However, besides more direct mechanisms involved in the development of
      therapeutic resistance, there are, in addition, indirect machineries that can
      cause barriers to therapies. These include hypoxia-mediated alterations in gene
      expression, proteomic and genomic changes, and clonal selection. These in turn
      can drive subsequent events that are known to further increase resistance to
      therapy in addition to critically affecting long-term prognosis.

PMID- 16594171
TI  - Monitoring metabolite gradients in the blood, liver, and tumor after induced
      hyperglycemia in rats with R3230 flank tumors using microdialysis and
      bioluminescence imaging.
AB  - Hypoxia is a common cause of reduced tumor response to treatment such as
      irradiation. The purpose of this study was to establish a method in a rat model
      that is clinically applicable to monitor the efficiency of glucose transport to
      both tumor and normal tissue following the induction of hyperglycemia. Female
      Fischer 344 rats bearing subcutaneous R3230 rat mammary adenocarcinomas received
      glucose (1 g/kg in 200 mg/ml Normosol) injected in the femoral vein with an
      infusion pump at a rate of 0.1 ml/min. Microdialysis sampling was performed on
      all animals. The perfusion marker Hoechst 33342 was injected intravenously at a
      dose of 5 mg/kg ten minutes prior to sacrifice. After the last blood sample was
      collected, the tumor and liver were removed and snap frozen for bioluminescence
      imaging and the rat was sacrificed. Imaging bioluminescence was performed on
      cryosections of the tumor and liver of the animal to monitor local metabolite
      gradients and concentrations of glucose in relation to the perfused vasculature,
      as determined by injected Hoechst 33342. Microdialysis and bioluminescence show
      comparable data when monitoring the changes of blood, liver, and tumor glucose
      concentrations as a result of induced hyperglycemia.

PMID- 16594172
TI  - Possible protective effects of alpha-tocopherol on enhanced induction of reactive
      oxygen species by 2-methoxyestradiol in tumors.
AB  - Several non-surgical tumor treatment modalities produce their cytotoxic activity
      by generating reactive oxygen species (ROS). Anti-oxidative enzymes such as
      superoxide dismutase (SOD) or exogenously supplied antioxidants may therefore
      reduce the efficacy of these treatments. The aim of the present study was to
      analyze the impact of (i) inhibiting SOD using 2-methoxyestradiol (2-ME), or (ii)
      application of alpha-tocopherol, on the cellular damage induced by hyperthermia
      (HT) in experimental tumors. DS-sarcoma cells grew either in culture or as solid
      tumors subcutaneously implanted in rats. In vitro, DS-cells were incubated with 2
      ME, and cell proliferation, ROS formation, lipid peroxidation and apoptosis were
      measured. In vivo, DS-sarcomas were treated with a ROS-generating hyperthermia
      combined with 2-ME or alpha-tocopherol application. Inhibition of SOD by 2-ME in
      vitro induced pronounced oxidative injury resulting in reduced proliferation. In
      vivo, ROS-generating hyperthermia led to local tumor control in 23% of the
      animals. The additional inhibition of SOD by 2-ME increased the control rate by
      approximately 50%. Application of alpha-tocopherol was found to have no effect on
      local tumor control, either in combination with ROS-generating hyperthermia or
      when 2-ME was additionally applied. Inhibition of SOD during ROS-generating
      hyperthermia results in pronounced cell injury and an improved local tumor
      control whereas exogenously applied vitamin E seems not to have an impact on
      oxidative stress.

PMID- 16594173
TI  - Simultaneous NIR-EPR spectroscopy of rat brain oxygenation.
AB  - Changes in cerebral oxygenation were simultaneously monitored by electric
      paramagnetic resonance (EPR) oximetry and near-infrared spectroscopy (NIRS). The
      tissue oxygen tension (t-pO2) was measured with an L-band (1.2 GHz) EPR
      spectrometer with an external loop resonator and the concentration of
      oxyhemoglobin [HbO2] and deoxyhemoglobin [Hb] were measured with a full-spectral
      NIRS system. Mean cerebral hemoglobin saturation (SmcO2) was calculated from the
      absolute [HbO2] and [Hb]. Six adult male rats were implanted with lithium
      phthalocyanine (LiPc) crystals into the left cerebral cortex. The change in
      oxygenation of the brain was induced by altering the inspired oxygen fraction
      (FiO2) in air from 0.30 at baseline to 0.0, 0.05, 0.10, and 0.15 for 1, 2, 5, and
      5 minutes, respectively, followed by reoxygenation with an FiO2 = 0.30. Although
      both t-pO2 and SmcO2 values showed a decrease during reduced FiO2 followed by
      recovery on reoxygenation, it was found that SmcO2 recovered more rapidly than t
      PO2 during the recovery phase. The recovery of t-pO2 is not only related to blood
      oxygenation, but also to delivery, consumption, and diffusion of oxygen into the
      tissue from the vascular system. Further studies will be required to determine
      the exact mechanisms for the delay between the recovery of SmcO2 and t-pO2.

PMID- 16594174
TI  - Microcirculation and reperfusion injury in organ transplantation.
AB  - There are many interesting aspects regarding hemorheology and tissue oxygenation
      in organ transplantation (such as liver, kidney, heart, etc.). The ischemia
      reperfusion injury syndrome is a very important problem. Much damage in organs
      appears to be induced by reperfusion injury syndrome. In fact, not only
      immunological etiopathogenesis but also biochemically-mediated microcirculation
      alterations can modulate the organ damage induced by ischemia-reperfusion injury
      during organ transplantation. During ischemia-reperfusion injury, xanthine
      oxidase activity, the increase in oxygen free-radicals, and the activation of
      neuthrophils are all very important. Platelet activating factor (PAT) and LTB4
      (promoting neuthrophils adhesiveness), activated by the xanthine oxidase-derived
      oxidants during reperfusion, activates the final post-ischemia injury. Much
      research is necessary in order to gain a fuller knowledge of the microcirculation
      conditions and oxygenation during organ transplantation.

PMID- 16594175
TI  - Focusing on genomic and phenomic correlations in respiration of non-melanotic
      skin cancers.
AB  - In recent years, with the development of techniques in modem molecular biology,
      it has become possible to study the genetic basis of carcinogenesis down to the
      level of DNA sequence. Major advances have been made in our understanding of the
      genes involved in cell cycle control and descriptions of mutations in those
      genes. These developments have led to the definition of the role of specific
      oncogenes and tumour suppressor genes in several cancers, including, for example,
      colon cancers and some forms of breast cancer. Work reported from our laboratory
      has led to the identification of a number of candidate genes involved in the
      development of non-melanotic skin cancers. In this chapter, we attempt to further
      explain the observed (phenomic) alterations in metabolic pathways associated with
      oxygen consumption with the changes at the genetic level.

PMID- 16594176
TI  - Protein C production: metal ion/protein interfacial interaction in immobilized
      metal affinity chromatography.
AB  - Protein C (PC) is an essential blood factor in the human blood coagulation
      cascade. PC can help achieve blood hemostasis in many deadly disease conditions
      such as sepsis, cancer, HIV, etc.; reduced oxygen transport due to blood
      agglutination within the body can cause tissue death and organ failure as a
      result of low oxygen transport. Our goal is to produce large quantities of low
      cost zymogen PC for the treatment and prevention of blood clotting resulting from
      many disease states, as well as provide an effective therapy for PC deficiency.
      Current studies show that Immobilized Metal Affinity Chromatography (IMAC) has
      high specificity and can be used for difficult separations among homologous
      proteins at relatively low cost compared to current methods, such as
      Immunoaffinity Chromatography. Thus, we are investigating the optimization of
      IMAC for the separation and purification of PC from Cohn fraction IV-I. Molecular
      interactions within the chromatography column involve many parameters that
      include: the use and type of chromatographic gel and buffer solution, the pH,
      temperature, metal ion, chelator, and the sequence and structure of the protein
      itself. These parameters all influence the protein's interaction with the column.
      Experimental equilibrium isotherms show that PC has primary and secondary binding
      characteristics, demonstrating that the interaction is not just a simple process
      of one protein binding to one metal ion. Understanding the thermodynamics of
      interfacial interaction between proteins and surface-bound Cu2+ is essential to
      optimizing IMAC for PC purification, as well as for separation of other proteins
      in general. Hence we are undertaking theoretical and experimental studies of IDA
      Cu/PC adsorption. The differences in structures of PC and other critical
      homologous blood factors are examined using the protein visualization program
      Cn3D. A better understanding of the interfacial phenomena will help determine the
      most effective conditions to achieve our goal.

PMID- 16594177
TI  - Modeling behavior of protein C during and after subcutaneous administration.
AB  - Protein C is an important blood factor protein that regulates the blood
      coagulation process. Deficiency of protein C can lead to excessive coagulation
      that results in lack of tissue oxygenation, causing conditions such as deep vein
      thrombosis, pulmonary embolism, and stroke. Human protein C has been approved as
      a treatment for congenital protein C deficiency; however, the therapy requires
      frequent injections, due to the short residence time of the protein. Subcutaneous
      administration has been examined as an alternative to increase residence time and
      decrease injection frequency, thereby creating a more patient-friendly dosing
      regimen. In order to design an efficient injection or infusion protocol for
      subcutaneously administered proteins, it is important to accurately model the
      behavior (absorption, distribution, elimination) of these proteins in the body.
      However, several factors involved in a subcutaneous injection of the protein make
      modeling this behavior a challenging task. For example, absorption of the drug
      from the subcutaneous site into the blood stream can be variable depending on the
      site of injection, physical activity of the patient, etc. Furthermore,
      degradation of the protein can occur at the site of injection and further modify
      its absorption. The objective of this work was to demonstrate the utility of
      frequency response modeling as an alternative method to analyze the behavior of
      subcutaneously administered protein C. The results of our study indicate that if
      the dose range yielding the constant clearance of protein C is identified for the
      patient, models of that type, as presented in our study, can be used to adjust
      optimal dosing of protein C necessary to reach prescribed levels of the protein
      in this patient at desired time points, both specified by treatment requirements.

PMID- 16594181
TI  - Center for American Nurses. Serving the needs of nurses today & tomorrow.

PMID- 16594178
TI  - Mechanisms for vasoconstriction and decreased blood flow following intravenous
      administration of cell-free native hemoglobin solutions.
AB  - Acellular free hemoglobin-based oxygen carriers (HBOC) are being developed as red
      cell substitutes. However, following intravenous administration of some HBOC,
      decreased systemic blood flow and decreased functional capillary density have
      been observed. In isolated blood vessels, hemoglobin (Hb) in solution free of
      erythrocyte membranes has been shown to elicit vascular contraction. Therefore,
      the decreased blood flow and functional capillary density may be due to inherent
      vasoactive property of native Hb. There are two plausible mechanisms for the Hb
      mediated vasoconstriction: nitrosylation of heme-irons and S-nitrosation of
      reactive beta-chain cysteines (Cys93beta). In this study, we investigated whether
      Hb Cys93beta thiols play a role in Hb-mediated vascular contraction using
      functional bioassays with isolated rat thoracic aorta. To better define the roles
      of globin thiols and heme-iron, Hbs modified at the heme-iron and/or Cys93beta
      sites were prepared and their vasoactivities tested. In addition, vasoactivities
      of natural heme proteins with heme and/or cysteine sites unavailable for NO
      reaction were also examined.

PMID- 16594182
TI  - NDNA Nursing Education Council. In support of non-traditional pediatric clinical
      practice settings for student nurses.

PMID- 16594183
TI  - What is health literacy?

PMID- 16594184
TI  - Health literacy and understanding medical information.

PMID- 16594185
TI  - Nurse staffing.

PMID- 16594188
TI  - What can we learn from the death of Terri Schiavo?

PMID- 16594187
TI  - Introduction to key concepts: cultural competence/proficiency.

PMID- 16594189
TI  - Identification of patients with noncancer diseases for palliative care services.
AB  - OBJECTIVE: To identify criteria for measuring the eligibility of patients with
      end-stage noncancer diseases for palliative care services in Australian
      residential aged care facilities. METHODS: No validated set if guidelines were
      available so five instruments were used: an adaptation of the American National
      Hospice Association Guidelines; a recent adaptation of the Karnofsky Performance
      Scale; the Modified Barthel Index; the Abbey Pain Score for assessment of people
      who are nonverbal and a Verbal Descriptor Scale, also for pain measurement. In
      addition, nutritional status and the presence of other problematic symptoms and
      their severity were also sought. RESULTS: The adapted American National Hospice
      Association Guidelines provided an initial indicative framework and the other
      instruments were useful in providing confirmatory data for service eligibility
      and delivery.

PMID- 16594190
TI  - Factors associated with difficulties encountered by nurses in the care of
      terminally ill cancer patients in hospitals in Japan.
AB  - OBJECTIVE: To identify the factors associated with difficulties encountered by
      nurses working in general wards in hospitals in Japan. METHODS: Questionnaires
      including items regarding difficulties in providing care to terminally ill cancer
      patients, the existence of a mentor regarding end-of-life issues, awareness of
      end-of-life issues, and demographic factors were administered to 375 staff nurses
      working in general in-patient wards. Multivariate regression analyses were
      employed to investigate correlations between factors. RESULTS: Multivariate
      regression analysis revealed that the existence of a mentor for end-of-life
      issues was associated with fewer difficulties in all areas other than "Knowledge
      and skill of nurses." Clinical experience was inversely related to difficulties
      in "Communication with patients and families" and "Personal issues." Greater
      awareness of end-of-life issues was related to higher difficulties in most areas.
      SIGNIFICANCE OF RESULTS: The existence of a mentor was correlated with fewer
      difficulties in most areas. Support by a palliative care team might be effective
      in reducing difficulties experienced by nurses and in improving care for
      terminally ill cancer patients. Basic communication training undertaken sooner
      after registration might be also useful.

PMID- 16594191
TI  - Sleep disturbances in palliative cancer patients attending a pain and symptom
      control clinic.
AB  - OBJECTIVE: The nature of sleep disturbances in palliative cancer patients has not
      been delineated clearly or fully understood due to limited clinical information.
      The purpose of this study was to describe sleep disturbance patterns, treatments,
      and communication in an advanced cancer outpatient population attending a pain
      and symptom control clinic. METHOD: One hundred oncology outpatients who came for
      consultation at a multidisciplinary pain and symptom control clinic were asked
      and agreed to complete a self-report questionnaire that elicited information
      about their sleeping habits, sleep concerns, sleep enhancement strategies, and
      related communication with health care providers. RESULTS: The majority of
      participants (72%) reported a wide variety of sleep disturbances, after cancer
      diagnosis, with the three most frequent elevated symptoms (> or = 5) being not
      feeling rested in the morning (72%), difficulty staying asleep (63%), and
      difficulty falling asleep (40%). Approximately one-fifth of participants (19%)
      reported having insomnia problems prior to their cancer diagnosis. In a
      correlational comparison with four other symptoms (i.e., fatigue, pain, anxiety,
      depression), the three highest correlations were between difficulty falling
      asleep and fatigue (r = 0.612), early awakening and fatigue (r = 0.596), and
      difficulty falling asleep and anxiety (r = 0.572). Fifty-three percent of
      participants reported using a variety of interventions for their sleep problems,
      the most frequent being sleep medication (37%). Of the 52 participants who
      reported an elevated level of concern about their sleeping difficulties (> or =
      5), 48 (92%) discussed their concerns with a health care provider. However, of
      the 20 participants with elevated symptoms (> or = 5) and low levels of concern
      (<5), only 7 (35%) communicated their concerns to a health care provider.
      SIGNIFICANCE OF RESULTS: The results of this study underline the importance of
      routine clinical assessments to detect sleep problems and interventions designed
      specifically to improve the overall sleep quality of cancer patients.

PMID- 16594192
TI  - Social aspects of caregiving for people living with motor neurone disease: their
      relationships to carer well-being.
AB  - OBJECTIVE: To investigate social aspects of caregiving for people living with
      motor neurone disease (MND) and examine their relationships to carers' well
      being. METHODS: A questionnaire was developed to assess carers' perceptions of
      their social support network (the Caregiver Network Scale, CNS), including
      measures of sociodemographic status and general well-being (GHQ-12), and mailed
      to carers of people living with MND. RESULTS: Seventy-five surveys were returned
      (response rate: 33%). In univariate analyses, relationships between well-being
      and carer age, time as caregiver, and four subscales of the CNS were found to be
      significant. However, multivariate analyses combining their effects revealed that
      stress on carer social networks was the best single contributor to predictions of
      carer well-being. SIGNIFICANCE OF RESULTS: Results indicate that prolonged caring
      for others living with MND has substantial costs for the carer in terms of loss
      of social support, which affects carer well-being and impacts ultimately on those
      living with MND. The CNS offers promise as a measure for screening at-risk
      carers; those who are distressed become candidates for professional intervention
      to help them cope better. Further research, providing validation of the scale for
      this task, is recommended.

PMID- 16594193
TI  - Victims of physical abuse among patients with cancer referred to psychiatric
      clinic in a cancer center hospital: a pilot study.
AB  - OBJECTIVE: Physical abuse is one of the most important public health problems,
      but little is known about physical abuse of cancer patients. The objects of this
      study are (1) to identify whether cancer patients have sustained physical abuse;
      (2) to explore clinical characteristics of the abused patients. METHODS: We
      reviewed 584 cancer patients referred to our psychiatry clinic by a cancer center
      hospital and investigated whether there were victims of physical abuse among
      these patients. We also investigated psychiatric characteristics of the abused
      patients. RESULTS: Of these 584 patients, three patients were recognized as
      victims of physical abuse at the time of referral. The perpetrator of physical
      abuse was their husband (domestic violence) in all three cases. All three
      patients had sustained physical abuse from their husbands for years before being
      diagnosed with cancer. In addition to physical abuse, all three patients had
      sustained emotional abuse (e.g., threat or intimidation) from their husbands.
      Psychiatric diagnoses of all three patients fulfilled the DSM-IV criteria for
      post-traumatic stress disorder (PTSD) and the traumatic event was mainly physical
      abuse by their husbands. SIGNIFICANCE OF RESULTS: Oncologists and psychiatrists
      should pay greater attention to the psychosocial and environmental problems of
      cancer patients and inquire about the presence of physical abuse in suspected
      cases. Medical staff should also know that early multidisciplinary interventions
      in addition to cancer treatments are needed for victims of physical abuse among
      cancer patients and that these interventions are necessary to improve compliance
      with treatment and proper decision making.

PMID- 16594194
TI  - Challenging the representations of cancer pain: experiences of a
      multidisciplinary pain management group in a palliative care unit.
AB  - OBJECTIVE: This article describes how a Multidisciplinary Pain Management Group
      was set up in a palliative care unit, and outlines the ways that the group works
      with different patients. We place these comments in the context of the wider
      representations of pain. METHODS: Our observations of patients seen by the
      multidisciplinary team. RESULTS: We tentatively propose that where the patient's
      pain has certain characteristics it may require a different approach. Patients
      who are older, with a lengthy treatment history, may require a different input
      than younger patients, who may have a number of factors that further complicate
      their experience of pain. We use our extensive experience with mesothelioma
      patients to draw a further important distinction between this patient group and
      other patients. SIGNIFICANCE OF RESEARCH: Our observations suggest the need to
      allow sufficient time for intensive psychological work to be done with
      mesothelioma patients in order for pharmacological interventions to be effective.

PMID- 16594195
TI  - Neuroleptic malignant syndrome in cancer treatment.
AB  - OBJECTIVE: Neuroleptic malignant syndrome (NMS) is a life-threatening reaction to
      neuroleptics. Several prospective studies have reported NMS occurrence rates
      ranging from 0.07% to 2.2% of patients receiving neuroleptics. However, few
      occurrences of NMS have been reported in cancer patients despite frequent
      complications of cancer and its treatment by mental disorders managed with
      neuroleptic drugs. Exhaustion, dehydration, and malnutrition are considered risk
      factors for NMS, and cancer patients represent a high risk group for NMS.
      METHODS: We describe a patient with metastatic chondrosarcoma who had received
      frequent neuroleptic injections prior to brain surgery and developed NMS in the
      intensive care unit immediately after surgery. The patient showed delirium,
      hyperpyrexia, tachycardia, diaphoresis, and extrapyramidal symptoms. After a
      diagnosis of NMS was made, supportive care and careful monitoring were carried
      out, and the patient recovered over an interval of 11 days. RESULTS AND
      SIGNIFICANCE OF THE RESEARCH: Clinical NMS studies have been conducted mainly in
      psychiatric units, but NMS can occur wherever psychotropic drugs are
      administered. NMS can be difficult to diagnose due to multiple complicating
      factors in cancer treatment, but the diagnosis is highly important given the risk
      of death. Recognition of prodromal NMS symptoms can facilitate actions to
      decrease morbidity and mortality. It is suggested that special attention to
      cancer patients undergoing psychopharmacologic treatment is required in clinical
      oncologic practice.

PMID- 16594196
TI  - The firmament of consciousness.

PMID- 16594197
TI  - Balancing life and death: hope and despair.

PMID- 16594198
TI  - A biomechanical investigation of the static stabilisers of the glenohumeral joint
      in the dog.
AB  - The aim was to determine the relative contribution of the glenohumeral
      ligaments/joint capsule complex and the limited joint volume/adhesion-cohesion
      (UV/AC) mechanisms to the static stability of the canine glenohumeral joint
      (GHJ). The GHJ of 32 complete cadaver specimens were manipulated to determine the
      presence of gross laxity (> 2mm translation) at joint angles of 150 degrees, 135
      degrees and 90 degrees. Following the removal of the peri-articular muscles,
      laxity was measured by applying a 15N force to the scapula in a variety of
      directions whilst the humerus was fixed to a jig. This was repeated for the
      abovementioned angles in intact joints and after venting and flushing to
      eliminate the UV/AC mechanisms. Results of clinical palpation and biomechanical
      studies were compared. Manipulation revealed a marked variation between joints
      although there was a tendency for progressive laxity as the joint was flexed.
      This finding was supported by the biomechanical study that also demonstrated no
      significant difference between intact and vented joints except in a cranio-caudal
      direction at 135 degrees and 90 degrees, and in a medial/lateral direction at 135
      degrees. Static stabilisers permitted a wide range of motion. Individual clinical
      palpations did not correlate well with biomechanical findings. Manipulation was
      difficult to perform and is unlikely to be a reliable method for determining
      subtle joint laxity. The static stabilisers do not appear to play a significant
      role in providing joint constraint during normal range of motion (except
      extension). Diagnoses of pathological laxity attributable to the static
      stabilisers should be made with caution and surgical treatments should take
      cognizance of the above-mentioned biomechanical features.

PMID- 16594199
TI  - Mechanical effects of high density polyethylene dynamic compression plate hole
      inserts on bone-plate constructs.
AB  - This study was conducted in order to investigate the mechanical effects of high
      density polyethylene screw hole inserts in 4.5 mm Dynamic Compression Plate (DCP)
      -synthetic bone constructs. A mid-shaft 'osteotomy' was created in synthetic bone
      cylinders. The bisecting 'osteotomy' was reduced using six-hole broad DCPs and
      4.5 mm cortical bone screws. The screws adjacent to the 'osteotomy' were placed
      using a load-guide. The remaining screws were placed in neutral position. High
      density polyethylene DCP screw hole inserts were incorporated with each screw in
      neutral position, in the experimental group. The bone plate constructs were
      tested in four point cyclical bending with the plates loaded at 2,000 Newtons,
      for a total of 6,000 cycles. Osteotomy gap was measured at 3,000 and 6,000
      cycles. Screw head deflection adjacent to the osteotomy was measured. Kruskal
      Wallis non-parametric testing was used for statistical comparisons. There was
      significantly less gapping at the osteotomy site in the treatment group after
      3,000 cycles (0.49 +/- 0.18 mm [control] vs. 0.06 +/- 0.14 mm [treated], P=0.02)
      and 6,000 cycles (0.6 +/- 0.18 mm [control] vs. 0.1 +/- 0.22 mm [treated],
      P=0.02). The screws adjacent to the gap were significantly more deformed in the
      control group than those in the treated constructs (3.63 +/- 1.81 [control] vs.
      1.06 +/- 1.55 [treated], P=0.0002). The polyethylene inserts improved the
      interface between bone plate and screw head, resulting in decreased relative
      movement of the implant and bone. The polyethylene inserts also resulted in less
      bending of the loaded screws.

PMID- 16594200
TI  - Cytokine profile in canine immune-mediated polyarthritis and osteoarthritis.
AB  - The purpose of this study was to determine the cytokine profile in 21 dogs with
      canine immune-mediated polyarthritis (IMA) and 15 dogs with osteoarthritis (OA)
      caused by cranial cruciate ligament rupture (CCLR). The mRNA expression of
      interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18,
      interferon (IFN)-gamma, transforming growth factor (TGF)-beta, and tumour
      necrosis factor (TNF)-alpha were analysed in synovial fluid by semi-quantitative
      RT-PCR, while TNF-alpha protein was determined by L929 cytotoxicity assay. The
      frequency of lymphocytes was analysed using FACScan. Both disorders reveal a
      similar cytokine expression pattern, except for significant lower IL-1beta
      expression in OA. Th1 cytokines IL-2 and IFN-gamma were detected, while IL-4 was
      nearly absent in IMA and OA. Furthermore, the bioassay demonstrates a
      significantly higher production of TNF-alpha in synovial fluid of dogs with IMA,
      compared to dogs with OA (p < 0.05). The frequency of CD4+, CD8+ and MHC class
      II+ cells was relatively higher in synovial fluids compared to peripheral blood
      in IMA. These findings reveal that the difference between the cytokine pattern of
      canine IMA and OA seems to be rather quantitative than qualitative. Both joint
      disorders show predominance of pro-inflammatory cytokines and absence of TH2
      cytokine expression, indicating the potential of IL-4 for a gene therapeutic
      approach.

PMID- 16594201
TI  - Isometry of potential suture attachment sites for the medial aspect of the
      tibiotarsal joint.
AB  - The isometry of the bipartite medial collateral ligament of the tarsus and two
      methods of stabilization by prosthetic ligament were assessed by measuring the
      change in distance between the origin and the insertion through full range of
      joint motion of the ligament and prosthetic ligaments. The single suture
      technique was isometric when the distal site was located at the centre of the
      trochlea of the talus. This site can only be used when the medial malleolus,
      which overlies the talus, is missing or removed. Whilst some length changes occur
      with hock motion, the double suture technique may be advocated in instances where
      the medial malleolus is present.

PMID- 16594202
TI  - Computerized tomography compared with radiography in the diagnosis of lateral
      trochlear ridge talar osteochondritis dissecans in dogs.
AB  - In this retrospective study, we compared the value of radiographic and
      computerized tomographic (CT) imaging for the diagnosis of lateral trochlear
      ridge talar osteochondritis dissecans (LTRT-OCD) in 11 tarsocrural joints. The
      flexed dorsoplantar skyline and the planta-rolateral-dorsomedial projections were
      the most reliable for radiographic detection of OCD fragments (in 7 of the 11
      joints). Overall, radiography detected OCD fragments in 8 of 11 joints. By
      contrast, the OCD fragments could be visualized and exactly localized by CT in
      all 11 joints. Computerized tomography allowed the talar ridges to be inspected
      without superimposition of any bony structures. This information may be very
      useful when minimal invasive techniques are used to treat LTRT-OCD lesions. The
      findings of this study suggest that CT is superior to radiography for making a
      diagnosis of LTRT-OCD in the dog.

PMID- 16594203
TI  - The ComPact UniLock 2.0/2.4 system and its clinical application in small animal
      orthopedics.
AB  - This study describes the titanium ComPact UniLock 2.0/2.4 locking plate system
      (Stratec Medical, Oberdorf, Switzerland) and reports its application in nine
      selected clinical cases. The system was found useful for a variety of
      indications. Three categories of clinical applications are illustrated. They
      include (a) long bone fractures, (b) cervical spinal fractures and instabilities
      and (c) joint instabilities and luxations. A brief introduction to the system has
      already been published

PMID- 16594204
TI  - Disease modifying treatment for feline rheumatoid arthritis.
AB  - Feline erosive polyarthritis includes the more common periosteal proliferative
      polyarthritis (PPP) and the rarely seen rheumatoid arthritis (RA) (11). During
      the past three years, 12 patients with definite feline rheumatoid arthritis,
      which did not respond well to conventional therapy, were treated with 7.5 mg of
      Methotrexate and 70 mg Leflunomide, given weekly by the oral route. The average
      age of the cats was 5.9 years (range 2.5 to 10 years). Siamese cats were over
      represented. Seven of the 12 (58%) cats showed a marked improvement, usually
      within four weeks. Once maximum improvement was obtained the dosage was
      decreased. Serious toxicity was not noted and carcinogenetic effect was not seen
      during the course of this study.

PMID- 16594205
TI  - Transient benign osteopetrosis in a calf persistently infected with bovine virus
      diarrhoea virus.
AB  - A two-day-old Simmental calf was admitted suffering from a fracture of the right
      femur. The radiographs showed striking changes in all bones, evident as alter
      noting zones of dense and less dense tissue (bone-in-bone) in the right femur and
      striped densities in the vertebral bodies. A stainless steel plate was used to
      repair the fracture, which healed well. The calf developed normally but was
      diagnosed as persistently infected with bovine virus diarrhoea (BVD) virus. It
      was kept in isolation and examined physically and radiographically during the
      following 13 months. The radiographic changes diminished during the first three
      months and at 13 months were barely visible. The animal was euthanatized, and
      immunohistochemistry revealed BVD virus antigen in numerous tissues. The
      radiographic abnormalities seen in this case are similar to those of the
      transient form of osteopetrosis in humans. Osteopetrosis in humans is currently
      thought to have a genetical cause, whereas it appears to be associated with viral
      disease in animals.

PMID- 16594206
TI  - Traumatic avulsion fracture of the lesser trochanter in a dog.
AB  - A 15-month-old 25 kg female spayed American Staffordshire Terrier was examined to
      determine the cause of a six month period of lameness of the left pelvic limb.
      Signs of severe pain were evident on hyperextension and simultaneous internal
      rotation or abduction of the left hip joint; crepitus or instabiltiy was not
      detected. The diagnosis of avulsion fracture of the lesser trochanter was based
      on radiographs, computed tomography (CT) and magnetic resonance imaging (MRI),
      supported by initial findings such as lameness and hip joint pain in extension.
      The dog was treated with strict confinement for eight weeks followed by a gradual
      increase in activity; non-steroidal anti-inflammatory drugs were given for one
      month. Three months later, the dog was clinically sound and unrestricted activity
      was resumed. Soundness was confirmed on follow-up 18 months after injury. CT and
      especially MRI were powerful diagnostic tools to identify chronic iliopsoas
      strains with an avulsion fracture of the lesser trochanter. Complete recovery
      ensued following conservative treatment only, despite the proximal diplacement of
      an avulsed segment of the lesser trochanter. Thus, traumatic injury to the
      iliopsoas muscle and to the lesser trochanter should be included as differential
      diagnosis in cases of hind leg lameness.

PMID- 16594207
TI  - Fixation of a proximal femoral physeal fracture in a dog using a ventral approach
      and two Kirschner wires.
AB  - A Salter-Harris type I proximal femoral physeal fracture was diagnosed in a six
      month-old Norfolk Terrier. The fracture was reduced using a ventromedial approach
      to the hip joint and fixation with two small Kirschner wires applied from the
      joint surface and countersunk below the cartilage. The ventromedial approach
      minimizes soft-tissue and vascular damage and affords direct visualization of the
      fracture, facilitating reduction and fixation. The two-year postoperative outcome
      was considered satisfactory in this case.

PMID- 16594208
TI  - Fibrosarcoma over the tarsal groove of a 14-month-old Quarter horse.
AB  - A 14-month-old male Quarter horse was presented for evaluation of a grade 3 out
      of 5 (grade 0 = sound; grade 5 = non-weight bearing) right rear lameness. A firm,
      8 x 16 cm mass was palpable at the caudal medial aspect of the distal tibia and
      proximal tarsal region of the right hind limb. A percutaneous needle aspirate
      contained mesenchymal cells that were moderate to large in size with single,
      oblong nuclei. Differential diagnoses included fibrous hyperplasia, fibroma, or
      well-differentiated fibrosarcoma. Excisional biopsy for both definitive diagnosis
      and treatment was offered and selected by the owner. A fibrosarcoma was confirmed
      by histological examination of the mass. One and a half years after resection
      signs of lameness or evidence of regrowth of the mass were not evident.

PMID- 16594209
TI  - The feline humerus. An anatomical study with relevance to external skeletal
      fixator and intramedullary pin placement.
AB  - The humeri of eleven feline cadavers were dissected and safe anatomical areas for
      placing external skeletal fixator pins were determined. Relevant measurements
      taken of the humeral condyle enabled a determination of a safe pin diameter range
      of 1.5 to 2.2 mm for transcondylar pins. Further anatomical measurements allowed
      recommendations to be made to angle pins in the distal humerus in a distolateral
      proximomedial direction so that the ESF pin penetrates the for cortex at least 20
      mm proximal to the medial epicondyle in order to avoid pin penetration of the
      supracondylar foramen. Cross sections taken of the distal humerus revealed that
      passage of an IM pin into the medial aspect of the humeral condyle was possible
      in less than half the cases.

PMID- 16594210
TI  - Arthrodesis of the talocalcaneal joint for the treatment of two horses with
      talocalcaneal osteoarthritis.
AB  - Two horses with lameness due to tolocalcaneal osteoarthritis that failed to
      respond to conservative management were treated by tolocalcaneal arthrodesis
      using cortex screws placed in lag fashion. The affected joint of one horse was
      arthrodesed by compressing and stabilizing the medial facet of the joint with
      three screws. In the second horse, the medial and lateral facets of the affected
      tolocalcaneal joint were each compressed and stabilized with two screws. The
      lameness of both horses improved markedly following surgery.

PMID- 16594211
TI  - Comparison of radiographic arthritic changes associated with two variations of
      tibial plateau leveling osteotomy.
AB  - Osteoarthritis (OA) progresses in the canine cranial cruciate ligament (CCL)
      deficient stifle. Progression of OA is also documented in canine patients after
      various surgical repair techniques for this injury. We evaluated the radiographic
      arthritic changes in canine stifle joints that have sustained a CCL injury, and
      compared radiographic OA scores between Tibial Plateau Leveling Osteotomy
      (TPLO)surgery patients receiving a medial parapatellar exploratory arthrotomy for
      CCL remnant removal versus those receiving a limited caudal medial arthrotomy
      without removal of the CCL remnants. Medial/lateral and caudal/cranial stifle
      radiographs were obtained before surgery, immediately following TPLO surgery and
      at 7-38 months (mean 20.5) after surgery. Sixty-eight patients (72 stifles) were
      included in the study. The cases were divided into two groups. The patients in
      group 1 (n = 49 patients, 51 stifles) had a limited caudal medial arthrotomy, and
      patients in group 2 (n = 19 patients, 21 stifles) had a medial parapatellar open
      arthrotomy. A previously described radiographic osteoarthritis scoring system was
      used to quantify changes in both of the groups. The age, weight, OA scores,
      initial tibial plateau angle, final tibial plateau angle, and the change in angle
      were compared between the groups. The results showed that there was significantly
      less progression of OA in the group that had the limited caudal medial,
      arthrotomy, versus a medial parapatellar open arthrotomy. There was a significant
      advancement of the OA scores of patients that had TPLO surgery.

PMID- 16594213
TI  - Third metacarpal bone mineral density assessment in the standing horse by dual X
      ray absorptiometry: suitability, precision and accuracy.
AB  - Bone mineral density (BMD) is correlated to mechanical properties of bone. In the
      horse, dual energy X-ray absorptiometry (DXA) has yet only been performed ex
      vivo, but a new portable DXA device would be ideal for in-vivo BMD measurement.
      We explored field suitability, precision and accuracy of this device for in-vivo
      third metacarpal density assessment. Precision was analysed by calculating
      measurement variation under repeated measurement tests with (reproducibility) and
      without (repeatability) limb repositioning. Repeatability and reproducibility
      were tested ex-vivo, at the same time that intra- and inter-operator
      reproducibility were assessed in-vivo. In order to test accuracy, bone mineral
      content (BMC) of several bone samples determined by DXA and ashing were compared.
      Repeatability was 1.47% and reproducibility 1.69% ex-vivo. In-vivo
      reproducibility varied between 2.91 and 4.06% for intra-operator test and between
      3.13 and 5.53% for inter-operator test. BMC measured by DXA and ash weight were
      highly correlated (R2>0.99). In conclusion, under described conditions this DXA
      device is usable, accurate and precise. Its sensitiveness reaches 8.23% in an
      individual longitudinal monitoring. Using the third metacarpal bone as an
      example, we have shown that this device is suitable for experimental or clinical
      monitoring.

PMID- 16594212
TI  - Use of the AO veterinary mini 'T'-plate for stabilisation of distal radius and
      ulna fractures in toy breed dogs.
AB  - The use of the AO (Arbeitsgemeinschaft fur Osteosynthesefragen) veterinary mini
      'T'-plate for stabilisation of distal radius and ulna fractures in toy breed dogs
      was evaluated in a retrospective study. All of the 14 dogs in the study weighed
      3.5 kg or less. The AO mini 'T'-plate was used as the final means of fixation in
      all cases. It was used as the primary form of stabilisation in ten dogs, and in
      four dogs it was used at revision surgery. In all cases, of the fractures healed.
      Return to function was graded 'as excellent' in six cases, 'good' in four and
      'fair' in two. Two dogs were lost to long-term follow up. It was concluded that
      the AO veterinary mini 'T'-plate is a suitable choice of implant for
      stabilisation of distal radius and ulna fractures in toy breed dogs, especially
      when the distal fragment is very small.

PMID- 16594214
TI  - Biomechanical evaluation of a veterinary suture anchor in the canine cadaver
      pelvis and femur.
AB  - A commercially available veterinary suture anchor was tested in the acetabula and
      femurs of canine cadavers. Size #2 suture anchor constructs were compared to a
      traditional screw and Teflon spiked washer constructs in a model of coxofemoral
      luxation repair. The screw/washer constructs failed at a higher maximum load than
      the #2 anchor constructs. In the acetabulum, significant differences in strength
      were also found in the position of the implant and in the direction of pull. The
      constructs in a more caudal position, and constructs pulled 90 degrees to the
      axis of insertion, failed at higher loads. The predominant mode of failure of the
      constructs was a suture failure. In the femur, size #5 suture anchors were used
      in a model of cranial cruciate ligament repair and collateral ligament repair.
      The anchor constructs failed predominantly by anchor pull-out in the distal
      femur. The constructs pulled 90 degrees to the axis of insertion were stronger
      than construcs pulled at 0 degrees to the axis of insertion. Varying the location
      of the implant in the femur did not affect the maximum load to failure.

PMID- 16594215
TI  - The effect of pelvic osteotomy plate type on axial rotation of the acetabular
      segment in the triple pelvic osteotomy.
AB  - OBJECTIVE: The purpose of this study is to evaluate the changes in structural
      anatomy of cadaver pelves, with specific emphasis on axial rotation, resulting
      from the application of TPO plates differing by type, angle and orientation.
      SAMPLE POPULATION: Nine cadaver pelves procedure: The degree of axial rotation
      was determined for three different pelvic osteotomy plate types, four different
      plate angles and two different orientations of the same plate. RESULTS: The
      observed degree of axial rotation was significantly different than the degree of
      axial rotation predicted by the plate angle for each group except the Rooks
      pelvic osteotomy plate. CONCLUSIONS/CLINICAL RELEVANCE: In the triple pelvic
      osteotomy the final degree of axial rotation may be significantly different than
      the predetermined plate angle.

PMID- 16594216
TI  - A Salter Harris type II fracture of the distal ulna in a fourteen month female
      neutered Great Dane.
AB  - A displaced Salter Harris type II fracture of the distal ulna and a minimally
      displaced Salter Harris type II fracture of the distal radius were diagnosed in a
      fourteen month female neutered Great Dane dog. Fracture reduction was challenging
      but treatment was successful. Aetiology of the unusual fracture is discussed.
      Long bone physes may close later in giant breeds, early neutering can cause a
      further delay.

PMID- 16594217
TI  - Arthroscopic exploration and biopsy for diagnosis of septic arthritis and
      osteomyelitis of the coxofemoral joint in a dog.
AB  - A five-year-old, spayed female mixed breed (38 kg) dog was referred for total hip
      replacement for an intermittently non-weight bearing lameness of the left hind
      limb. Radiographs and computed tomography suggested proliferative, osteolytic
      pathology of the left coxofemoral joint. Using arthroscopic exploration and
      biopsy, septic arthritis and osteomyelitis in the left coxofemoral joint were
      diagnosed. Treatment recommendations for antibiotic therapy and femoral head and
      neck excision were made based upon this diagnosis. Femoral head and neck excision
      resulted in pain relief and improved function and arthroscopy provided a
      minimally invasive, yet accurate, diagnosis in this case.

PMID- 16594218
TI  - Bioartificial bone grafting: Tarsal joint fusion in a dog using a bioartificial
      composite bone graft consisting of beta-tricalciumphosphate and platelet rich
      plasma--a case report.
AB  - Grafting of large bone defects caused by trauma or tumor resection still remains
      a problem to solve. In experimental studies as well as in human dentistry,
      osteoconduction and biodegradation of the beta-tricalciumphosphate Cerasorb as
      well as osteoinductive capabilities of platelet rich plasma have been proven. In
      case of luxation of the right tarsal joint, including a compressive fracture of
      the forth tarsal bone, the recommended use of autologous cancellous bone to
      support osseous fusion was replaced by the use of a bioartificial bone graft.
      Biodegradation of the bone graft was proven clinically and radiographically.
      Complete osseous fusion of the intertarsal joint occurred. The use of the beta
      tricalciumphosphate Cerasorb in combination with platelet rich plasma to support
      a partial arthrodesis of the tarsal joint in a dog did not impede the healing
      process but led to full recovery of the patient, indicating that this concept of
      bioartificial bone grafting could support bone healing.

PMID- 16594219
TI  - Defending dignity.

PMID- 16594220
TI  - Hope in the general Norwegian population, measured using the Herth Hope Index.
AB  - OBJECTIVE: The aims of this study were to describe hope in a large sample that
      was drawn from the general Norwegian population and to examine how
      sociodemographic and health-related variables were related to hope. METHODS: Of
      4,000 adult citizens, randomly drawn from the National Register, 1,912 (49%)
      returned the Norwegian version of the Herth Hope Index (HHI). RESULTS: When
      demographic and health-related variables were controlled for, age, gender,
      marital status, and employment status were significantly related to hope. The
      most important health-related variable was self-assessed health status, with
      participants who were satisfied with their health reporting significantly higher
      levels of hope. Participants who indicated that they had a chronic disease
      reported significantly higher hope scores compared to those without a chronic
      disease. Older men, individuals who were receiving a pension or were unemployed,
      and individuals who were widowed or unmarried reported the lowest levels of hope.
      In this study, an individual's subjective evaluation of his/her health was the
      most important health-related predictor of hope. SIGNIFICANCE OF THE RESEARCH:
      The most important health-related variable that predicted hope was self-assessed
      health in that participants who were satisfied with their health reported higher
      levels of hope. This finding suggests that an individual's subjective assessment
      of health is a better predictor of hope than the presence a chronic disease.
      Knowledge about levels of hope in the general population can be used as reference
      values against which an individual score or a group mean may be compared.

PMID- 16594221
TI  - Caregiver unmet needs, burden, and satisfaction in symptomatic advanced cancer
      patients at a Veterans Affairs (VA) medical center.
AB  - OBJECTIVES: Caregiver outcomes among those caring for symptomatic advanced cancer
      patients at VA Medical Centers have not been well reported. The purposes of this
      study were (1) to identify the caregiver characteristics and their unmet needs;
      (2) to examine the association between caregiver unmet needs, caregiver burden,
      and caregiver satisfaction; and (3) to identify the independent predictors of
      different caregiver outcomes. METHODS: One hundred caregivers completed three
      caregiver outcomes instruments: Family Inventory of Needs (FIN), Care Strain
      Index (CSI), and Family Satisfaction with Advanced Cancer Care (FAMCARE). The
      caregivers' demographics and their function, depression, health status, and
      social support status as well as the caregivers' perception of the patients'
      unmet needs (PPUN) were obtained. Principal component analysis was performed to
      examine the underlying dimensions of caregiver outcome measures. Pearson
      correlation and stepwise multivariate regression analyses were performed.
      RESULTS: The median number of unmet needs was 2 and the median CSI score was 4.
      Most of unmet needs were related to information needs (needing more information
      related to home care, finding help with the problems at home, and disease
      prognosis) and symptom management. The majority of caregivers were satisfied or
      very satisfied by the care patients received. Spouse caregivers (N = 60, 60%)
      were significantly older (p = 0.006) with higher unemployment rates (p = 0.001),
      higher depression scores (p = 0.04), and lower social support scores (p < 0.0001)
      than nonspouse caregivers (N = 40, 40%). The PPUN predicted caregiver burden and
      the presence of caregiver unmet needs independently. The presence of caregiver
      unmet needs was the only independent predictor of caregiver satisfaction.
      Caregivers with a high PPUN and higher depression score experienced a higher
      burden. SIGNIFICANCE OF THE RESEARCH: The caregiver outcome model is proposed and
      needs to be further validated in a new cohort of caregivers.

PMID- 16594222
TI  - A chart review, pilot study of two single-item screens to detect cancer patients
      at risk for cachexia.
AB  - OBJECTIVE: Cachexia is a problematic wasting syndrome experienced by some cancer
      patients that can lead to early death in these patients. The purpose of the
      present study was to examine the criterion validity and sensitivity and
      specificity of two single items from a depression scale to rapidly screen
      patients in ambulatory oncology clinics for cancer-related nutritional risk and
      cachexia. METHODS: A chart review was conducted of 50 randomly selected patient
      profiles. Patients' responses to item 5 ("I eat as much as I used to") and item 7
      ("I notice I am losing weight") of the Zung Self Rating Depression Scale (ZSDS)
      were compared against the Scored Patient-Generated Subjective Global Assessment
      (PG-SGA) as well as to Body Mass Index (BMI) scores and weight at two time
      periods. RESULTS: Item 5 of the ZSDS was significantly related to initial weight
      (F3,45 = 6.06, p < 0.001), weight at 6-month follow-up (F3,27 = 4.16, p < 0.05),
      BMI score (F3,46 = 2.89, p < 0.05), and nutritional risk on the PG-SGA (F3,45 =
      5.80, p < 0.01). Item 7 of the ZSDS was only a significant predictor of
      nutritional risk as measured by the PG-SGA (F3,46 = 6.01, p < 0.01). When the two
      items were combined to form a two-item scale, it maintained the individual items'
      significant relationship to the PG-SGA (F1,48 = 13.99, p < 0.001). Using this as
      the criterion for identifying nutritionally at-risk patients, the two-item screen
      yields a sensitivity of 50% and specificity of 88%. SIGNIFICANCE OF THE RESEARCH:
      It is concluded that a single item or a combination of two items can yield a
      reliable initial screen for identifying patients who might be at nutritional risk
      for the development of cachexia. Further study is needed in prospective trials to
      further explore the utility of these items.

PMID- 16594223
TI  - Breathlessness in cancer and chronic obstructive pulmonary disease: using a
      qualitative approach to describe the experience of patients and carers.
AB  - OBJECTIVE: To investigate and document the effects of breathlessness on the
      everyday lives of patients with cancer and COPD and their carers. This subject
      has been little researched, although dyspnoea is recognized as a disabling,
      distressing symptom. The number of breathless people is increasing as patients
      with all types of cardio-respiratory disease live longer. METHODS: Patients with
      severe COPD and cancer and their carers were interviewed at home using a
      semistructured format to record their perceptions of the impact of
      breathlessness, the help they had received from medical and caring services, and
      their ideas on how these could be improved. RESULTS: 10 patients with COPD (6
      male) and 10 with cancer (6 male) and their spouses were interviewed. All
      patients found breathlessness frightening, disabling, and restricting. Patients
      developed a stoical, philosophical approach in order to live with dyspnoea and
      the difficulties it imposed: this was also an important way of reducing the
      emotional impact of breathlessness. Patients' spouses suffered significantly,
      experiencing severe anxiety and helplessness as they witnessed their partners'
      suffering and felt powerless to reduce it. The restrictions imposed by
      breathlessness affected their lives profoundly. Support of all kinds, practical,
      medical, and psychosocial was highly valued but was provided inconsistently and
      sporadically. Where help was given it came most frequently from general
      practitioners (GPs, family physicians) and specialist respiratory nurses.
      SIGNIFICANCE OF RESULTS: This study is the first to document the psychosocial
      needs of carers, which are not adequately recognized or addressed at present.
      Patients and carers may feel most isolated and need support outside the working
      hours of most services and future provision needs to reflect this. Patients with
      cancer experience a more rapid onset of breathlessness. More clinicians need to
      be educated in the management of chronic breathlessness so known helpful
      strategies are more widely employed.

PMID- 16594224
TI  - The prescription of opioid analgesics to terminal cancer patients: impact of
      physicians' general attitudes and contextual factors.
AB  - OBJECTIVE: This study aimed to examine factors associated with the prescription
      of opioid analgesics to terminal cancer patients, including physicians' general
      attitudes toward morphine and contextual factors. METHODS: A survey was conducted
      among a sample of French general practitioners (GPs) and oncologists. Respondents
      were asked to describe the last three terminally ill patients they had followed
      up to death. RESULTS: Overall, 526 GPs and oncologists (global response rate:
      57%) described 1,082 cancer patients, among whom 85.4% received opioid
      analgesics. Among other significant predictors (patient age, cancer type, family
      assistance), this prescription was less frequent for female patients followed by
      male physicians (OR = 0.53), and more frequent for patients followed by
      physicians trained in palliative care (OR = 2.70). On the other hand, physicians'
      attitudes toward morphine were not associated with prescription of morphine and
      other opioid analgesics. SIGNIFICANCE OF RESULTS: Although nonprescription of
      opioid analgesics is only a crude proxy measure for undertreatment of cancer
      pain, our findings suggest the need to develop training in palliative care in
      order to standardize practices among GPs and specialists. Our results also
      highlight the necessity to study pain assessment as an interaction between the
      physician and the patient, and to consider patients' and physicians' respective
      genders as a key variable within this interaction.

PMID- 16594225
TI  - A conceptual model and key variables for guiding supportive interventions for
      family caregivers of people receiving palliative care.
AB  - According to the World Health Organization, the patient and family should be
      viewed as the "unit of care" when palliative care is required. Therefore family
      caregivers should receive optimal supportive care from health professionals.
      However, the impact of supporting a dying relative is frequently described as
      having negative physical and psychosocial sequalae. Furthermore, family
      caregivers consistently report unmet needs and there has been a dearth of
      rigorous supportive interventions published. In addition, comprehensive
      conceptual frameworks to navigate the family caregiver experience and guide
      intervention development are lacking. This article draws on Lazarus and Folkman's
      seminal work on the transactional stress and coping framework to present a
      conceptual model specific to family caregivers of patients receiving palliative
      care. A comprehensive account of key variables to aid understanding of the family
      caregiver experience and intervention design is provided.

PMID- 16594226
TI  - Countertransference and ethics: a perspective on clinical dilemmas in end-of-life
      decisions.
AB  - Ethical dilemmas in end-of-life care, such as the request for assisted suicide,
      must be understood in the context of the relationship that exists between
      patients and the clinicians treating them. This context includes the way health
      professionals respond to the tasks in caring for a dying patient. This article
      reviews the literature exploring the factors the influence clinical decision
      making at the end of life. The interplay of ethics, countertransference and
      transference are explained in detail.

PMID- 16594228
TI  - Death of a generation.

PMID- 16594227
TI  - A medical revolution in death-hastening decisions.

PMID- 16594229
TI  - Beyond symptom control: research in psychosocial and existential issues in
      palliative care.

PMID- 16594230
TI  - Measuring quality of life at the end of life: validation of the QUAL-E.
AB  - OBJECTIVES: To validate the QUAL-E, a new measure of quality of life at the end
      of life. METHODS: We conducted a cross-sectional study to assess the instrument's
      psychometric properties, including the QUAL-E's associations with existing
      measures, evaluation of robustness across diverse sample groups, and stability
      over time. The study was conducted at the VA and Duke University Medical Centers,
      Durham, North Carolina, in 248 patients with stage IV cancer, congestive heart
      failure with ejection fraction < or = 20%, chronic obstructive pulmonary disease
      with FEV1 < or = 1.0 1, or dialysis-dependent end stage renal disease. The main
      outcome measures included QUAL-E and five comparison measures: FACIT quality of
      life measure, Missoula-VITAS Quality of Life Index, FACIT-SP spirituality
      measures, Participatory Decision Making Scale (MOS), and Duke EPESE social
      support scales. RESULTS: QUAL-E analyses confirmed a four-domain structure (25
      items): life completion (alpha = 0.80), symptoms impact (alpha = 0.87),
      relationship with health care provider (alpha = 0.71), and preparation for end of
      life (alpha = 0.68). Convergent and discriminant validity were demonstrated with
      multiple comparison measures. Test-retest reliability assessment showed stable
      scores over a 1-week period. SIGNIFICANCE OF RESULTS: The QUAL-E, a brief measure
      of quality of life at the end of life, demonstrates acceptable validity and
      reliability, is easy to administer, performs consistently across diverse
      demographic and disease groups, and is acceptable to seriously ill patients. It
      is offered as a new instrument to assist in the evaluation of the quality and
      effectiveness of interventions targeting improved care at the end of life.

PMID- 16594231
TI  - Physicians' practices related to the use of terminal sedation: moral and ethical
      concerns.
AB  - OBJECTIVE: Although terminal sedation (TS) has generally been seen as legal and
      ethically acceptable, ethical and moral issues remain. Little is known about the
      use of TS in general clinical practice and about how TS is viewed by physicians,
      given moral and ethical concerns. The objectives of this study are (1) to
      describe attitudes of physicians regarding terminal sedation; (2) to explore
      demographic characteristics, such as age, gender, subspecialty, and number of
      years in practice, that might be related to the use of TS; and (3) to compare
      physicians who have and have not used TS on the degree to which they view TS as
      moral and consistent with their professional and personal ethics. METHODS: An
      anonymous survey of New Jersey physicians was conducted at the University of
      Medicine and Dentistry of New Jersey-School of Osteopathic Medicine. A 39-item
      questionnaire assessing general opinions about, experiences with, and religious,
      moral, ethical attitudes toward TS and other end-of-life treatments was utilized.
      RESULTS: A majority of physicians (73%) had used TS for a patient. Most (93%)
      said there were circumstances under which they would use TS. With regard to
      questions about whether TS would be "immoral," "would violate my religious
      beliefs," "would violate my professional ethics" and "is inconsistent with the
      physician's role of preserving life," approximately 55% of those who have used TS
      disagreed; for those who have not used TS, approximately 35% disagreed.
      SIGNIFICANCE OF RESULTS: Professional education and opportunities for discussion
      appear necessary to help reconcile the conflicts raised in the use of this end-of
      life treatment strategy.

PMID- 16594232
TI  - Difficulties in screening for adjustment disorder, Part I: Use of existing
      screening instruments in cancer patients undergoing bone marrow transplantation.
AB  - OBJECTIVE: Although success rates for bone marrow transplantation (BMT) continue
      to improve, there is still a high level of morbidity and physical and emotional
      distress associated with BMT. To date, limited research has focused on the
      assessment of and screening for specific psychiatric disorders of patients facing
      BMT. This is especially true with regard to identifying adjustment disorder (AD),
      despite the fact that AD is the most prevalent psychiatric diagnosis in cancer
      patients. METHODS: A sample of 95 BMT patients were interviewed using the
      Structured Clinical Interview for Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition (SCID) and completed several commonly used self-report
      instruments to determine if these tools could be used to identify patients with
      adjustment disorder in need of further assessment and intervention. RESULTS: Of
      these patients, 34.7% were diagnosed with adjustment disorder, 11.6% with major
      depression, and 5.3% with generalized anxiety disorder. The instruments were not
      found to be predictive of AD. However, the results of a regression analysis
      showed that the Social Subscale of the Functional Assessment of Cancer Therapy
      General (R2 delta = 0.04, F = 4.30, p < 0.05) was a significant predictor of
      adjustment disorder. SIGNIFICANCE OF RESULTS: We conclude that there is little
      efficacy in using existing scales for detecting adjustment disorders in cancer
      patients undergoing bone marrow transplantation, and that other tools for
      identifying patients with adjustment disorder who might benefit from counseling
      are needed.

PMID- 16594233
TI  - Difficulties in screening for adjustment disorder, Part II: An attempt to develop
      a novel self-report screening instrument in cancer patients undergoing bone
      marrow transplantation.
AB  - OBJECTIVE: Screening for adjustment disorder (AD) in cancer patients presents a
      significant clinical challenge. As seen in Part I of this research, conventional,
      existing measures are rather poor at detecting this most common of psychiatric
      diagnoses. Bone marrow transplantation (BMT) has a high level of morbidity that
      can cause significant stress for patients faced with the procedure. METHODS: A
      sample of 95 BMT patients completed a semistructured interview and a novel self
      report instrument, the Coping Flexibility Scale for Cancer (C-Flex), to determine
      if it could identify patients with adjustment disorder in need of further
      assessment and intervention. RESULTS: The screen yielded four factors but was not
      predictive of AD. However, the C-Flex was significantly related to the presence
      of any disorder (r = -0.44, p < 0.001) in this sample. In addition, Factor I of
      the screen was found to be correlated to the presence of any diagnosis (r = 
      0.44, p < 0.001) and to have adequate sensitivity (81.63%) and specificity
      (76.09%). SIGNIFICANCE OF RESULTS: Either because of problems with the scale or
      the amorphous nature of the AD category, or both, rapid identification of
      patients with this common problem has proven to be elusive.

PMID- 16594234
TI  - Hopelessness and terminal illness: the construct of hopelessness in patients with
      advanced AIDS.
AB  - OBJECTIVE: Understanding the construct of hopelessness in the context of a life
      threatening or terminal illness is a complex and challenging undertaking. The
      objective of this study was to examine the construct of hopelessness in patients
      with advanced AIDS by examining the structure of the Beck Hopelessness Scale in
      this specific population. METHODS: For the past three decades, the primary
      measure used to study hopelessness in a variety of populations has been the Beck
      Hopelessness Scale. Several factor analytic studies have been published using
      this scale, with studies of nonclinical samples typically describing a two-factor
      model (optimism and pessimism), whereas clinical samples have consistently
      generated a third factor (lack of motivation to make changes). We used
      confirmatory factor analysis to analyze two data sets in patients with AIDS.
      RESULTS: Confirmatory factor analysis of the Beck Hopelessness Scale in two
      samples of patients with far advanced AIDS revealed a clear superiority for a
      three-factor model. SIGNIFICANCE OF RESULTS: The Beck Hopelessness Scale has
      unique characteristics when applied to a terminally ill population. The
      implications of these results for studies of terminal illness are discussed.

PMID- 16594235
TI  - Children's and family needs of young women with advanced breast cancer: a review.
AB  - This article reviews literature about the impact of advanced breast cancer on
      children and families. It is clear that the adjustment of the family is
      influenced by disease stage and maternal adjustment, the needs of the particular
      child relating closely to their developmental stage. Interventions with children
      and families to promote adjustment when a parent has advanced cancer are also
      discussed, including implications for clinical practice.

PMID- 16594236
TI  - Clinical practice guidelines for the management of psychosocial distress at the
      end of life.
AB  - Algorithm-based clinical practice guidelines relating to psychiatric,
      psychosocial, and spiritual domains can effect a major improvement in end-of-life
      care by defining a gold standard for clinicians in an area not previously
      subjected to such a level of scrutiny. This article outlines the status of these
      guidelines and offers recommendations for policy development relative to doctor
      patient communication and management of distress (psychological, social,
      existential, spiritual) and psychiatric disorders. The arching principle of these
      standards and guidelines is the recognition that the physical and the
      psychosocial are interrelated and overlapping in end-of-life care, and that
      patients should receive their total care as a seamless integration of physical
      and supportive services.

PMID- 16594237
TI  - Conversion disorder with convulsion and motor deficit mimicking the adverse
      effects of high-dose Ara-C treatment in a posttransplant acute myeloid leukemia
      patient: a case report and review of the literature.
AB  - In this communication, we report an acute leukemia patient who developed
      conversion disorder mimicking the adverse effects of high-dose cytosine
      arabinoside (Ara-C) treatment after the patient received high-dose Ara-C
      treatment. A 21-year-old woman, with acute recurrent leukemia after bone marrow
      transplantation, received high-dose Ara-C treatment and 10 days later was
      referred for psychiatric consultation because of an abrupt onset of convulsion.
      On neurologic examination, she showed convulsion of all the limbs without loss of
      consciousness. All limbs looked paretic; however, tendon reflexes in all limbs
      were normal and pathological reflex was not recognized. When her hand was dropped
      onto her own face, it fell next to her face but not on her face. Laboratory data
      were unremarkable. She had no history of psychiatric illness or drug or alcohol
      abuse. The patient explained that she knew about the recurrence of her own
      leukemia and the news of the death of a close friend due to leukemia at the same
      time, which was a shocking event for her, focusing her attention on her own fears
      of dying from the same disease. Conversion disorder in cancer patients is not
      common; however, appropriate diagnosis is very important to avoid inappropriate
      examinations and treatments. In leukemia patients receiving chemotherapy, various
      kinds of signs and symptoms may develop due to the adverse effects of
      chemotherapy and/or infection. Therefore, conversion disorder might be overlooked
      and inappropriate treatment and examinations might be performed. Clinicians
      should consider conversion disorder in the differential diagnosis when patients
      develop unexplained neurological symptoms.

PMID- 16594238
TI  - Darkness and light: perspectives in palliative medicine.

PMID- 16594239
TI  - Reflections on life and death.

PMID- 16594240
TI  - Psycho-oncology and palliative care: opportunity for integration.

PMID- 16594241
TI  - Psychometric properties of the EORTC Quality of Life Questionnaire in inpatient
      cancer rehabilitation in Germany.
AB  - OBJECTIVE: Recent years have shown an increase in the use of questionnaires
      measuring health-related quality of life to verify the quality of treatment in
      the field of oncology. An often used cancer-specific questionnaire is the
      "Quality of Life Core Questionnaire of the European Organization for the Research
      and Treatment of Cancer" (EORTC QLQ-C30). The purpose of this study is to analyze
      the psychometric properties of the EORTC QLQ-C30 (version 1) in order to
      determine the feasibility and appropriateness for its use in inpatient cancer
      rehabilitation in Germany with heterogeneous diagnoses. METHODS: The
      questionnaire was administrated to a sample of 972 cancer patients at the
      beginning of treatment and to 892 patients after treatment. Besides descriptive
      analysis, the statistical analyses include confirmatory analysis and the
      multitrait/multimethod approach to test the questionnaire's postulated scale
      structure (factorial validity) and its reliability (internal consistencies). The
      analysis also includes a comparison of responsiveness indices (effect size,
      reliable change index) to test the sensitivity of the instrument. RESULTS: The
      EORTC QLQ-C30 showed satisfactory levels of reliability and sensitivity, but the
      postulated scale structure could not be confirmed. The results illustrate that
      the varimax-rotated solution of a principal component analysis does not confirm
      the scale structure postulated by the authors. Correspondingly, the selected fit
      indices within the scope of the confirmatory factor analysis do not show
      satisfactory results either. SIGNIFICANCE OF RESULTS: We therefore consider
      version 1 of the EORTC QLQ-C30 to be only limitedly useful for the routine
      assessment of changes in the quality of life of cancer patients in inpatient
      rehabilitation in Germany, especially because of the instrument's length and
      possible redundancies. For this reason, a scoring procedure limited to a subset
      of items is suggested, revealing satisfactory to good psychometric indices.
      However, further psychometric tests are necessary, especially with regard to
      validity and sensitivity.

PMID- 16594242
TI  - Mental health status of clients from three HIV/AIDS palliative care projects.
AB  - OBJECTIVE: To describe mental health status and its correlates among clients of
      three palliative care programs targeting underserved populations. METHODS: Mental
      Health Inventory (MHI-5) scores of clients from programs in Alabama (n = 39),
      Baltimore (n = 57), and New York City (n = 84) were compared. RESULTS: Mean MHI-5
      scores did not differ among sites and were indicative of poor mental health.
      Significant differences were noted among sites with regard to client
      sociodemographics, physical functioning, and perceptions of interpersonal
      relations. Results of multivariate regression models estimated for each site
      suggest variation in the relative importance of potential predictors among sites.
      Whereas poorer mental health was primarily associated with history of drug
      dependence at Baltimore and more physical symptomatology at New York, better
      mental health was most strongly correlated with more positive perceptions of
      interpersonal relationships at Baltimore and increasing age and more positive
      perceptions of meaning and purpose in life at New York. SIGNIFICANCE OF RESULTS:
      The data presented suggest the importance of assessing clients' history of and
      current need for mental health services. Evidence of a relationship between
      positive perceptions of meaning and purpose and better psychological function
      underscores the importance of existential issues for the overall well-being of
      those who are seriously ill.

PMID- 16594243
TI  - Humor and laughter in palliative care: an ethnographic investigation.
AB  - OBJECTIVE: Humor and laughter are present in most of human interaction.
      Interactions in health care settings are no exception. Palliative care
      practitioners know from experience that humor and laughter are common in
      palliative care despite the seriousness of the care context. Research
      establishing the significance of humor in care of the dying is limited. METHODS:
      Clinical ethnography conducted in a 30-bed inpatient palliative care unit served
      as the means of exploring the functions of humor in care of the dying. Clinical
      ethnography is intended for examination of the human experience of illness or of
      caregiving in an interpersonal context (Kleinman, 1992). The method emphasizes
      the subjective experience and the realm of communication and interaction for both
      patients and caregivers. Data were collected through participant observation,
      informal interviews with patients and families, and semistructured interviews
      with members of the health care team. RESULTS: Humor and laughter were widespread
      and important in the research setting. An overall attitude of good humor
      prevailed. Within that atmosphere, humor served myriad functions. Functions were
      identified in three overarching themes; building relationships, contending with
      circumstances, and expressing sensibility. Humor among patients, families, and
      staff most commonly served to build therapeutic relationships, relieve tension,
      and protect dignity and a sense of worth. Humor was particularly significant in
      maintaining collegial relationships, managing stressful situations, and
      maintaining a sense of perspective. SIGNIFICANCE OF RESULTS: Findings established
      the significance of humor and laughter as humanizing dimensions of care of the
      dying and contributes to the volume of research supporting evidence-based
      practice.

PMID- 16594244
TI  - A feasibility study of dignity psychotherapy delivered via telemedicine.
AB  - OBJECTIVE: Dignity Psychotherapy has shown great promise as a value-affirming
      intervention for patients with advanced disease. We delivered the Dignity
      Psychotherapy intervention in a feasibility study of a series of eight cancer
      patients via videophone technology to deliver the therapy into their homes.
      METHODS: Once eligible patients were consented on this IRB-approved study, they
      completed baseline assessments and were scheduled to have the videophone placed
      in their homes. The Dignity Therapy sessions then encompassed a first session,
      which was transcribed and edited, followed by a second session to go over the
      edited transcript and allow the patient to make changes. Patients then filled out
      follow-up questionnaires and had the telemedicine equipment removed from their
      homes, and their legacy document delivered. RESULTS: Participants had a mean age
      of 56.32 years (range = 41-66, SD = 7.65) and were diagnosed with lung (n = 5,
      62.5%), breast (n = 2, 25%), or colon cancer (n = 1, 12.5%). They reported
      overall benefit from the intervention along with a high level of satisfaction. We
      were able to deliver the intervention in a timely fashion, with minimal length
      between sessions and transcript delivery and few technical difficulties.
      SIGNIFICANCE OF RESULTS: Telemedicine can greatly extend the benefits of Dignity
      Psychotherapy by bringing it to patients who are dying at home. Our very
      preliminary work suggests that delivering the intervention to patients who are
      too ill to leave their homes or who are in rural locations may be a feasible way
      to help them.

PMID- 16594245
TI  - Competence development in palliative care in Norway: A description and evaluation
      of a postgraduate education program in palliative care in Drammen, Norway.
AB  - OBJECTIVE: The aim of the present study was to evaluate competence development in
      palliative treatment, nursing and care in students (n = 25) undergoing a two-year
      postgraduate education program in palliation at a university college in Norway.
      METHODS: A questionnaire was handed out on five occasions during the education
      period. RESULTS: Results showed that the students rated their competence level as
      between some competence and good competence before entering the course. However,
      the competence level rose throughout the course period, and at the end of their
      education most of the students perceived themselves at a very good or extremely
      good competence level. SIGNIFICANCE OF RESULTS: Statistically significant
      differences in all questions measuring competence in palliation were found on all
      occasions. Further studies are needed to confirm the effect of education on
      students' perceived competence development and whether it has a positive impact
      on clinical practice.

PMID- 16594246
TI  - The prevalence of psychiatric disorder and the wish to hasten death among
      terminally ill cancer patients.
AB  - OBJECTIVE: This study assessed the prevalence of psychiatric disorder among a
      group of terminally ill cancer patients with or without a wish to hasten death
      (WTHD). METHODS: Consecutive patient referrals to a hospice inpatient unit, home
      palliative care service, and hospital palliative care-consulting service were
      recruited. A group of these patients (n = 56) consented to participate in a
      structured clinical interview (SCID) to identify the presence of psychiatric
      diagnoses. Patients were categorised into those with or without a wish to hasten
      death. RESULTS: Current major depressive episode and adjustment disorder were the
      most prevalent disorders in this group of patients. Patients with a high WTHD
      were significantly more likely to have a current major depressive episode
      compared to patients with no WTHD. Patients with a high WTHD were also
      significantly more likely to have a past major depressive episode compared to
      patients with no WTHD. SIGNIFICANCE OF RESULTS: These results support the view
      that terminally ill patients with a high WTHD are significantly more likely to be
      suffering from a depressive disorder as assessed by a structured clinical
      interview. This has important clinical implications for those caring for dying
      patients who may make a request to hasten death.

PMID- 16594247
TI  - The delirium subtypes: a review of prevalence, phenomenology, pathophysiology,
      and treatment response.
AB  - Delirium is a highly prevalent disease in the elderly and postoperative, cancer,
      and AIDS patients. However it is often misdiagnosed and mistreated. This may be
      partly due to the inconsistencies of the diagnosis itself. Delirium is best
      defined currently by an association of cognitive impairment and arousal
      disturbance. Three subtypes (hyperactive, hypoactive, mixed) receive a definition
      in the literature, but those definitions may vary from author to author according
      to the importance they give either to the motoric presentation of the delirium or
      to the arousal disturbance. Our aim is to point out the inconsistencies we found
      in the literature, but also to identify different paths that have been explored
      to solve them, that is, the suggestion to emphasize the arousal disturbances in
      defining the subtypes instead of the motoric presentations, which seem to be more
      fluctuating, and because of the fluctuating course of the disease to extend the
      observation over a period of time, which may improve the accuracy of the
      diagnosis. This is not without importance from a clinical standpoint. Subtypes of
      delirium may be explained by different pathophysiologic mechanisms, which remain
      partly unexplained, and may respond to specific treatments. There is a trend to
      isolate core symptoms (disorientation, cognitive deficits, sleep-wake cycle
      disturbance, disorganized thinking, and language abnormalities) so as to
      distinguish them from secondary symptoms that may be correlated with the
      different etiologies. Our contribution is also to challenge, with new data, the
      accepted belief that psychotic features are quite rare in the hypoactive type of
      delirium. We demonstrate that delusions and perceptual disturbances, although
      less frequent, are present in more than half of the patients with hypoactive
      delirium. The psychotic features are clearly correlated with a highly prevalent
      rate of patients', spouses', and caregivers' distress. The mixed subtype of
      delirium seems to have the worst prognosis, the hyperactive showing the best
      prognosis. The treatment of the agitated delirious patient is also more
      consensual. Haloperidol remains the gold standard in the treatment of delirium
      regardless of the clinical presentation, but the literature provides several
      alternatives that may prove more specific and have less adverse effects (atypical
      antipsychotics, psychostimulants, anesthetics).

PMID- 16594248
TI  - Issues in psychotherapy with terminally ill patients.
AB  - Psychotherapy with the terminally ill poses special challenges for clinicians and
      in return offers unique rewards. As a time limited therapy, acceptance, rather
      than change is a primary goal; yet, patients can be strongly motivated to change.
      Patients may need to struggle with how to disengage while also maintaining
      connection. Unique transference and countertransference issues arise. The
      psychological tasks of dying include grieving, saying goodbye, constructing a
      meaningful context to one's life, and letting go. The therapist can serve as a
      companion and guide to the dying person as she or he negotiates these tasks.
      Through the use of a case example, these issues are explored from the
      perspectives of patient and therapist. The therapist must address the following
      issues: attending to physical suffering, differentiating between grieving and
      depression, addressing fears, facilitating the life review, and assisting in
      decision making. A dying patient's need to leave a legacy, complete
      relationships, grapple with spiritual and religious issues, and attend to his or
      her family, are often important themes. Therapists must work productively with
      denial, maintain flexible yet appropriate boundaries, grapple with their own
      anxiety about death, and grieve the loss of their patients. Psychotherapy with
      dying patients can help reduce their psychological pain, relieving psychosocial
      distress and providing opportunities for personal growth in the last stage of
      life. Such work is often draining yet immensely rewarding for the patient and
      therapist alike.

PMID- 16594249
TI  - Improving care at the end of life: how advance care planning can help.
AB  - Based on a comparison of studies of patient desires regarding end-of-life care
      and of the actual course of end-of-life care, this article concludes that there
      is a significant discrepancy in the United States between the kind of care most
      people want and the kind of care they in fact receive. The article offers a case
      example to illustrate one type of dilemma commonly encountered in end-of-life
      care. It then introduces and describes the practice of advance care planning. Use
      of advance care planning, it is argued, can prevent moral dilemmas and improve
      end-of-life care.

PMID- 16594250
TI  - Psychostimulants and delirium in patients receiving palliative care.
AB  - The use of psychostimulants to relieve opioid-induced drowsiness and symptoms of
      depression in medically ill patients has become increasingly established in North
      America. The role of psychostimulants in the care of patients receiving
      palliative care is beginning to be debated in the United Kingdom both in the
      hospice and hospital setting. Delirium has been well defined and reported as a
      significant problem in populations of patients receiving palliative care. Two
      case histories are presented to illustrate the potential benefit of
      psychostimulants in hypoactive delirium.

PMID- 16594251
TI  - Cancer and personhood.

PMID- 16594252
TI  - Rediscovering the meaning in medicine: lessons from the dying on the ethics of
      experience.
AB  - Modern medicine is currently confronting a crisis of meaning that is manifesting
      in a dispirited and demoralized profession. Palliative medicine and the care of
      patients with incurable diseases provide clinicians with an opportunity to
      rediscover the meaning in their work. In particular, with its emphasis on
      compassion, palliative medicine reconnects us to the Socratic ideal and an
      "ethics of experience." Our rediscovery of this perennial philosophy is necessary
      if we are to develop the wisdom necessary to containing our enormous scientific
      capabilities.

PMID- 16594253
TI  - Learning and memory.
AB  - Learning and memory processes are thought to underlie a variety of human
      psychiatric disorders, including generalised anxiety disorder and post-traumatic
      stress disorder. Basic research performed in laboratory animals may help to
      elucidate the aetiology of the respective diseases. This chapter gives a short
      introduction into theoretical and practical aspects of animal experiments aimed
      at investigating acquisition, consolidation and extinction of aversive memories.
      It describes the behavioural paradigms most commonly used as well as
      neuroanatomical, cellular and molecular correlates of aversive memories. Finally,
      it discusses clinical implications of the results obtained in animal experiments
      in respect to the development of novel pharmacotherapeutic strategies for the
      treatment of human patients.

PMID- 16594254
TI  - Animal models of anxiety.
AB  - Animal models for anxiety-related behavior are based on the assumption that
      anxiety in animals is comparable to anxiety in humans. Being anxious is an
      adaptive response to an unfamiliar environment, especially when confronted with
      danger or threat. However, pathological variants of anxiety can strongly impede
      the daily life of those affected. To unravel neurobiological mechanisms
      underlying normal anxiety as well as its pathologi- cal variations, animal models
      are indispensable tools. What are the characteristics of an ideal animal model?
      First, it should display reduced anxiety when treated with anxiolytics
      (predictive validity). Second, the behavioral response of an animal model to a
      threatening stimulus should be comparable to the response known for humans (face
      validity). And third, the mechanisms underlying anxiety as well as the
      psychological causes should be identical (construct validity). Meeting these
      three requirements is difficult for any animal model. Since both the
      physiological and the behavioral response to aversive (threatening) stimuli are
      similar in humans and animals, it can be assumed that animal models can serve at
      least two distinct purposes: as (1) behavioral tests to screen for potential
      anxiolytic and antidepressant effects of new drugs and (2) tools to investigate
      specific pathogenetic aspects of cardinal symptoms of anxiety disorders. The
      examples presented in this chapter have been selected to illustrate the potential
      as well as the caveats of current models and the emerging possibilities offered
      by gene technology. The main concepts in generating animal models for anxiety
      that is, selective breeding of rat lines, experience-related models, genetically
      engineered mice, and phenotype-driven approaches-are concisely introduced and
      discussed. Independent of the animal model used, one major challenge remains,
      which is to reliably identify animal behavioral characteristics. Therefore, a
      description of behavioral expressions of anxiety in rodents as well as tests
      assays to measure anxiety-related behavior in these animals is also included in
      this chapter.

PMID- 16594255
TI  - Genetic alterations of the murine serotonergic gene pathway: the
      neurodevelopmental basis of anxiety.
AB  - The relative contribution of genetic and environmental factors in the
      configuration of behavioral differences is among the most prolonged and
      contentious controversies in intellectual history. Although current views
      emphasize the joint influence of genes and environmental sources during early
      brain development, the physiological complexities of multiple gene-gene and gene
      environment interactions in the developmental neurobiology of fear and anxiety
      remain elusive. Variation in genes coding for proteins that control serotonin (5
      hydroxytryptamine, 5-HT) system development and plasticity, establish 5-HT neuron
      identity, and modulate 5-HT receptor-mediated signal transduction as well as
      cellular pathways have been implicated in the genetics of anxiety and related
      disorders. This review selects anxiety and avoidance as paradigmatic traits and
      behaviors, and it focuses on mouse models that have been modified by deletion of
      genes coding for key players of serotonergic neurotransmission. In particular,
      pertinent approaches regarding phenotypic changes in mice bearing inactivation
      mutations of 5-HT receptors, 5-HT transporter, and monoamine oxidase A and other
      genes related to 5-HT signaling will be discussed and major findings highlighted.

PMID- 16594256
TI  - Mutagenesis and knockout models: hypothalamic-pituitary-adrenocortical system.
AB  - Hyperactivity of central neuropeptidergic circuits such as the corticotropin
      releasing hormone (CRH) and vasopressin (AVP) neuronal systems is thought to play
      a causal role in the etiology and symptomatology of anxiety disorders. Indeed,
      there is increasing evidence from basic science that chronic stress-induced
      perturbation of CRH and AVP neurocircuitries may contribute to abnormal neuronal
      communication in conditions of pathological anxiety. Anxiety disorders aggregate
      in families, and accumulating evidence supports the notion that the major source
      of familial risk is genetic. In this context, refined molecular technologies and
      the creation of genetically engineered mice have allowed us to specifically
      target individual genes involved in the regulation of the elements of the CRH
      (e.g., CRH peptides, CRH-related peptides, their receptors, binding protein).
      During the past few years, studies performed in such mice have complemented and
      extended our knowledge. The cumulative evidence makes a strong case implicating
      dysfunction of CRH-related systems in the pathogenesis of anxiety disorders and
      depression and leads us beyond the monoaminergic synapse in search of eagerly
      anticipated strategies to discover and develop better therapies.

PMID- 16594257
TI  - Mutagenesis and knockout models: NK1 and substance P.
AB  - Tachykinins play an important role as peptide modulators in the CNS. Based on the
      concentration and distribution of the peptides and their receptors, substance P
      (SP) and its cognate receptor neurokinin 1 (NK1R) seem to play a particularly
      important role in higher brain functions. They are expressed at high levels in
      the limbic system, which is the neural basis of emotional responses. Three
      different lines of evidence from physiological studies support such a role of SP
      in the regulation of emotionality: (1) stress is often associated with elevated
      level of SP in animals and humans; (2) systematic and local injections of SP
      influence anxiety levels in a dose-dependent and site-specific manner; (3) NK1
      receptor antagonists show anxiolytic effects in different animal models of
      anxiety. Although these studies point to the NK1 receptor as a promising target
      for the pharmacotherapy of anxiety disorders, high affinity antagonists for the
      human receptors could not be studied in rats or mice due to species differences
      in the antagonist binding sites. However, studies on anxiety and depression
      related behaviors have now been performed in mouse mutants deficient in NK1
      receptor or SP and NKA. These genetic studies have shown that anxiety and
      depression-related phenotypes are profoundly affected by the tachykinin system.
      For example, NK1R-deficient mice seem to be less prone depression-related
      behaviors in models of depression, and one study also provided evidence for
      reduced anxiety levels. Mice deficient in SP and NKA behaved similarly as the
      NK1R knockouts. In animal models of anxiety they performed like wildtype mice
      treated with anxiolytic drugs. In behavioral paradigms related to depression they
      behaved like wildtype animals treated with antidepressants. In summary, the
      genetic studies clearly show that the SP/NK1 system plays an important role in
      the modulation of emotional behaviors.

PMID- 16594258
TI  - Genetic epidemiology of anxiety disorders.
AB  - This chapter reviews the genetic epidemiology of the major subtypes of anxiety
      disorders including panic disorder, phobic disorders, generalized anxiety
      disorder, and obsessive-compulsive disorder. Controlled family studies reveal
      that all of these anxiety subtypes are familial, and twin studies suggest that
      the familial aggregation is attributable in part to genetic factors. Panic
      disorder and, its spectrum have the strongest magnitude of familial clustering
      and genetic underpinnings. Studies of offspring of parents with anxiety disorders
      an increased risk of mood and anxiety disorders, but there is far less
      specificity of the manifestations of anxiety in children and young adolescents.
      Although there has been a plethora of studies designed to identify genes
      underlying these conditions, to date, no specific genetic loci have been
      identified and replicated in independent samples.

PMID- 16594259
TI  - Interactions between corticotropin-releasing hormone and serotonin: implications
      for the aetiology and treatment of anxiety disorders.
AB  - The amount of evidence for a role of aberrant serotoninergic neurotransmission in
      the aetiology of anxiety disorders, such as generalised anxiety and panic
      disorder, has been increasing steadily during the past several years. Although
      the picture is far from complete yet--partly due to the large number of serotonin
      (5-HT) receptors and the often-disparate effects of receptor agonists and
      antagonists in animal models of anxiety--SSRIs and the 5-HT1A agonist buspirone
      have now earned their place in the treatment of anxiety disorders. However, these
      drugs show--as they do in depressed patients--a delayed onset of improvement.
      Therefore, new therapeutical strategies are being explored. Corticotropin
      releasing hormone (CRH), which plays a key role in the autonomic, neuroendocrine
      and behavioural responses to stress, is a strong anxiogenic neuropeptide and a
      promising candidate for therapeutical intervention in anxiety disorders. The
      neuroanatomical localisation of CRH, its congeners (the urocortins) and their
      receptors within the serotoninergic raphe nuclei suggests that interactions
      between the CRH system and 5-HT may play a role in fear and anxiety. In this
      chapter, I will discuss studies from my own and other laboratories showing that
      CRH and the urocortins influence several aspects of serotoninergic
      neurotransmission, including the firing rate of 5-HT neurones and the release and
      synthesis of this monoamine. Moreover, the interactions between CRH and 5-HT
      during psychologically stressful challenges will be discussed. Finally, I will
      review data showing that long-term alterations in the CRH system lead to aberrant
      functioning of serotoninergic neurotransmission under basal and/or stressful
      conditions. From this growing set of data the picture is emerging that the CRH
      system exerts a vast modulatory influence on 5-HT neurotransmission. An aberrant
      cross-talk between CRH and 5-HT may be of crucial importance in the neurobiology
      of anxiety disorders and represents, therefore, a promising goal for
      therapeutical intervention in these psychiatric diseases.

PMID- 16594260
TI  - Anxiety disorders: noradrenergic neurotransmission.
AB  - The past decade has seen a rapid progression in our knowledge of the
      neurobiological basis of fear and anxiety. Specific neurochemical and
      neuropeptide systems have been demonstrated to play important roles in the
      behaviors associated with fear and anxiety-producing stimuli. Long-term
      dysregulation of these systems appears to contribute to the development of
      anxiety disorders, including panic disorder, posttraumatic stress disorder
      (PTSD), and social anxiety disorder. These neurochemical and neuropeptide systems
      have been shown to have effects on distinct cortical and subcortical brain areas
      that are relevant to the mediation of the symptoms associated with anxiety
      disorders. Moreover, advances in molecular genetics portend the identification of
      the genes that underlie the neurobiological disturbances that increase the
      vulnerability to anxiety disorders. This chapter reviews clinical research
      pertinent to the neurobiological basis of anxiety disorders. The implications of
      this synthesis for the discovery of anxiety disorder vulnerability genes and
      novel psychopharmacological approaches will also be discussed.

PMID- 16594261
TI  - Pathophysiology and pharmacology of GABA(A) receptors.
AB  - By controlling spike timing and sculpting neuronal rhythms, inhibitory
      interneurons play a key role in brain function. GABAergic interneurons are highly
      diverse. The respective GABA(A) receptor subtypes, therefore, provide new
      opportunities not only for understanding GABA-dependent pathophysiologies but
      also for targeting of selective neuronal circuits by drugs. The pharmacological
      relevance of GABA(A) receptor subtypes is increasingly being recognized. A new
      central nervous system pharmacology is on the horizon. The development of
      anxiolytic drugs devoid of sedation and of agents that enhance hippocampus
      dependent learning and memory has become a novel and highly selective therapeutic
      opportunity.

PMID- 16594262
TI  - Excitatory amino acid neurotransmission.
AB  - In recent years great progress has been made in understanding the function of
      ionotropic and metabotropic glutamate receptors; their pharmacology and potential
      therapeutic applications. It should be stressed that there are already N-methyl-D
      aspartate (NMDA) antagonists in clinical use, such as memantine, which proves the
      feasibility of their therapeutic potential. It seems unlikely that competitive
      NMDA receptor antagonists and high-affinity channel blockers will find
      therapeutic use due to limiting side-effects, whereas agents acting at the
      glycineB site, NMDA receptor subtype-selective agents and moderate-affinity
      channel blockers are far more promising. This is supported by the fact that there
      are several glycineB antagonists, NMDA moderate-affinity channel blockers and
      NR2B-selective agents under development. Positive and negative modulators of AMPA
      receptors such as the AMPAkines and 2,3-benzodiazepines also show more promise
      than e.g. competitive antagonists. Great progress has also been made in the field
      of metabotropic glutamate receptors since the discovery of novel, allosteric
      modulatory sites for these receptors. Selective agents acting at these
      transmembrane sites have been developed that are more drug-like and have a much
      better access to the central nervous system than their competitive counterparts.
      The chapter will critically review preclinical and scarce clinical experience in
      the development of new ionotropic and metabotropic glutamate receptor modulators
      according to the following scheme: rational, preclinical findings in animal
      models and finally clinical experience, where available.

PMID- 16594263
TI  - Neurobiology and treatment of anxiety: signal transduction and neural plasticity.
AB  - The stress-dependence and chronic nature of anxiety disorders along with the
      anxiolytic effectiveness of antidepressant drugs suggests that neuronal
      plasticity may play a role in the pathophysiology of anxiety. Intracellular
      signaling pathways are known in many systems to be critical links in the cascades
      from surface signals to the molecular alterations that result in functional
      plasticity. Chronic antidepressant treatments can regulate intracellular
      signaling pathways and can induce molecular, cellular, and structural changes
      over time. These changes may be important to the anxiolytic effectiveness of
      these drugs. In addition, the signaling proteins implicated in the actions of
      chronic antidepressant action, such as cAMP response element binding protein
      (CREB), have also been implicated in conditioned fear and in anxiety. The
      cellular mechanisms underlying conditioned fear indicate roles for additional
      signaling pathways; however, less is known about such mechanisms in anxiety. The
      challenge to identify intracellular signaling pathways and related molecular and
      structural changes that are critical to the etiology and treatment of anxiety
      will further establish the importance of mechanisms of neuronal plasticity in
      functional outcome and improve treatment strategies.

PMID- 16594264
TI  - Neuropeptides in anxiety modulation.
AB  - This review is focused on the involvement of neuropeptides in the modulation of
      physiological and pathological anxiety. Neuropeptides play a major role as
      endogenous modulators of complex behaviours, including anxiety-related behaviour
      and psychopathology, particularly due to their high number and diversity, the
      dynamics of release patterns in distinct brain areas and the multiple and
      variable modes of interneuronal communication they are involved in. Manipulations
      of central neuropeptidergic systems to reveal their role in anxiety (and often
      comorbid depression-like behaviour) include a broad spectrum of loss-of-function
      and gain-of-function approaches. This article concentrates on those neuropeptides
      for which an involvement as endogenous anxiolytic or anxiogenic modulators is
      well established by such complementary approaches. Particular attention is paid
      to corticotropin-releasing hormone (CRH) and vasopressin (AVP) which, closely
      linked to stress, neuroendocrine regulation, social behaviour and
      learning/memory, play critical roles in the regulation of anxiety-related
      behaviour of rodents. Provided that their neurobiology, neuroendocrinology and
      molecular-genetic background are well characterized, these and other
      neuropeptidergic systems may be promising targets for future anxiolytic
      strategies.

PMID- 16594265
TI  - Neuroendocrine aspects of PTSD.
AB  - This chapter discussed how neuroendocrine findings in posttraumatic stress
      disorder (PTSD) potentially inform hypothalamic-pituitary-adrenal (HPA)
      alterations in PTSD and highlight alterations relevant to the identification of
      targets for drug development. Most studies demonstrate alterations consistent
      with an enhanced negative feedback inhibition of cortisol on the pituitary, an
      overall hyperreactivity of other target tissues (adrenal gland, hypothalamus), or
      both in PTSD. However, findings of low cortisol and increased reactivity of the
      pituitary in PTSD are also consistent with reduced adrenal output. The
      observations in PTSD are part of a growing body of neuroendocrine data providing
      evidence of insufficient glucocorticoid signaling in stress-related
      neuropsychiatric disorders.

PMID- 16594266
TI  - Anxiety disorders: clinical presentation and epidemiology.
AB  - This chapter gives an overview of the clinical presentation of anxiety disorders
      and reviews basic epidemiological knowledge on them. The presented knowledge is
      largely related to the classification of anxiety disorders as presented by the
      Diagnostic and Statistical Manual of Mental Disorders since itsthird revision
      (DSM-III). Without going into detail into the history of the classification of
      anxiety disorders and into the history and development of the several editions of
      the Diagnostic Manual of Mental Disorders (DSM) of the American Psychiatric
      Association (APA) it should just briefly be mentioned that the DSM of the APA has
      undergone until today four revisions. Within these revisions, the third edition
      (DSM-III) changed most radically from the forerunning ones. The major change in
      DSM-III was that the category "anxiety neurosis" was deleted because this term
      was too general and could not be defined reliably. On the basis of evidence that
      imipramine can block panic attacks, panic disorder was created as a new diagnosis
      for the first time in DSM-III. Anxiety states without spontaneous panic attacks
      were separated from panic disorder and defined as a residual category,
      generalized anxiety disorder. The revised version of DSM-III, DSM-III-R, was
      published in 1987, and the fourth and most recent edition, DSM-IV, was published
      in 1994. More recently, a text revision of DSM-IV has been published that does
      not entail changes to the diagnostic criteria of disorders, but provides updated
      empirical reviews for each diagnostic category regarding associated features,
      cultural, age, and gender features, prevalence, course, familial patterns, and
      differential diagnosis (DSM-IV-R). Without going into further details of the
      development and changes across the different editions and revisions of DSM--these
      have been reviewed comprehensively in other reviews--this chapter gives an
      overview about the clinical presentations of anxiety disorders by referring
      mainly to the forth edition of the DSM (DSM-IV 1994). In the second part, the
      chapter reviews and summarizes selected aspects (prevalence, correlates, risk
      factors and comorbidity) of epidemiological knowledge on anxiety disorders.

PMID- 16594267
TI  - Transcultural issues.
AB  - Pharmacogenetics as a field of research is increasing the basis of knowledge on
      the use of psychotropics in different ethnic patient populations. This chapter
      summarizes current knowledge on the metabolism of anxiolytic agents with emphasis
      on pharmacogenetics and ethnic variations in drug responses.

PMID- 16594269
TI  - Pharmacotherapy of anxiety.
AB  - The pharmacological treatment of anxiety has a long and chequered history, and
      recent years have seen a rich development in the options available to
      prescribers. Most of the currently used anxiolytic agents act via monoaminergic
      (chiefly serotonin) or amino acid (GABA or glutamate) neurotransmitters, and this
      chapter describes the pharmacology of the major drug groups. Clinical
      applications are discussed with respect to the five major anxiety disorders, as
      well as simple phobia and depression with concomitant anxiety. Prospective future
      developments in the field are considered.

PMID- 16594268
TI  - Challenge studies in anxiety disorders.
AB  - In psychiatry, the use of pharmacological challenges in panic disorder is unique
      in that the clinical phenomenon of central interest (i.e., the panic attack) can
      be provoked readily and assessed in the clinical laboratory setting. During the
      past 20 years pharmacological challenge studies have increased our knowledge
      concerning the neurobiology of panic disorder remarkably and may ultimately
      result in novel and more causal treatment strategies. Moreover, the differences
      in sensitivity to certain panicogens such as serotonergic agents, lactate, carbon
      dioxide and cholecystokinin tetrapeptide are likely to be fruitful in serving as
      biological markers of subtypes of panic disorders and should be a major focus of
      research, as the identification of reliable endophenotypes is currently one of
      the major rate-limiting steps in psychiatric genetic studies.

PMID- 16594270
TI  - New pharmacological treatment approaches for anxiety disorders.
AB  - New developments in the pharmacological treatment of anxiety disorders will have
      distinct backgrounds: characterization of pathophysiological processes including
      evolving techniques of genomics and proteomics will generate new drug targets.
      Drug development design will generate new pharmacological substances with
      specific action at specific neurotransmitter and neuropeptide receptors or
      affecting their reuptake and metabolism. New anxiolytic drugs may target receptor
      systems that only recently have been linked to anxiety-related behavior. This
      includes the N-methyl-D-aspartate (NMDA), S-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA), and the cannabinoid receptors. In addition,
      signal transduction pathways, neurotrophic factors, and gases such as nitric
      oxide or carbon monoxide may be new drug targets. Combining psychopharmacological
      and psychotherapeutical interventions is a further field where benefits for the
      treatment of anxiety disorders could be achieved. Although the road of drug
      development is arduous, improvements in the pharmacological treatment of anxiety
      disorders are expected for the near future.

PMID- 16594271
TI  - Pharmacogenomics.
AB  - So far no pharmacogenetic/genomic study has been conducted specifically for
      anxiety disorders. Some of the presented results, however, do pertain to such
      disorders. For example, pharmacokinetic aspects of antidepressant drug therapy
      likely also apply to patients with anxiety disorders, and several genetic
      polymorphisms in the cytochrome P450 (CYP) gene family and drug transporter
      molecules, such as the multidrug resistance (MDR) gene type 1, have been reported
      to influence the pharmacokinetics of antidepressant drugs. At this stage of
      pharmacogenomics research, it is difficult to interpret the relevance of
      pharmacodynamic-genetic association studies conducted in depressed patients for
      anxiety disorders. A number of studies have reported an influence of
      polymorphisms of genes mostly in the serotonergic pathway on the response to
      antidepressant drugs in patients suffering from depression. In order to know
      whether they can be extrapolated to patients with anxiety disorders, clinical
      studies are warranted. Despite all the shortcomings of the currently available
      pharmacogenetic studies, this field holds great promise for the treatment of
      anxiety disorders. In the future, psychiatrists may be able to base treatment
      decisions (i.e., the type and dose of prescribed drug) on more objective
      parameters than only the diagnostic algorithms used now. This will limit unwanted
      side effects and adverse drug reactions, and could reduce time to response,
      resulting in a more individualized pharmacotherapy.

PMID- 16594272
TI  - Pharmacoproteomics.
AB  - Proteomics, the comprehensive analysis of the protein complement of the genome of
      an organism, is becoming an increasingly important discipline for the
      identification of disease targets. In addition, the effects of drug treatment and
      metabolism can now be studied on the protein level in a comprehensive manner.

PMID- 16594273
TI  - The effects of a control-enhancing intervention for nursing home residents:
      cognition and locus of control as moderators.
AB  - OBJECTIVE: This study aimed to clarify which older adults benefit most from a
      control-enhancing intervention; in particular, whether cognitive functioning or
      locus of control might moderate the benefit derived. METHODS: Nursing home
      residents were randomly assigned to two conditions: (1) a control-enhanced
      condition that provided the option of caring for a plant (n=10), and (2) a
      comparison condition that monitored any change under the standard of care (n=10).
      Comparison group participants were subsequently offered the intervention, which
      led to a total of 17 intervention participants. RESULTS: Cognitive function and
      locus of control were found to significantly moderate the effects of the control
      enhancing intervention on residents' perceived health competency, but not
      depression or life satisfaction. SIGNIFICANCE OF RESULTS: Interventions for
      nursing home residents could be tailored to fit specific needs. Screening for
      cognitive function and locus of control may help predict who is likely to benefit
      from control-enhancing interventions.

PMID- 16594274
TI  - Quality of life pilot intervention for breast cancer patients: use of social
      cognitive theory.
AB  - OBJECTIVE: The purpose of this article is to evaluate an 8-week pilot
      intervention based on Social Cognitive Theory to improve quality of life for
      women with breast cancer. METHODS: A total of 32 breast cancer patients were
      randomized to either the intervention or standard care. Outcome variables
      included quality of life, mood, self-efficacy, outcome expectations, and self
      regulation. RESULTS: Effect sizes were calculated to examine the impact of the
      intervention, with moderate to large effect sizes found for several subscales of
      the outcome expectations variable: learning about cancer and treatment (d =
      0.85), having a positive attitude (d = 0.54), talking about cancer (d = 1.02),
      engaging in relaxation (d = 0.62), and setting goals (d = 1.58). SIGNIFICANCE OF
      RESULTS: A nonparametric sign test was conducted, indicating that women in the
      intervention condition either improved more or showed less decline than the women
      in standard care, p = .034, two-tailed. Implications and suggestions for the
      content and delivery of future psychosocial interventions with cancer patients
      are reviewed.

PMID- 16594275
TI  - A communication tool for cancer patients with pain: the art therapy technique of
      the body outline.
AB  - OBJECTIVE: The multidimensional aspect of pain suggests the use of multimodal
      interventions. The Memorial Sloan-Kettering Cancer Center has recently utilized
      the art therapy modality to help patients communicate the painful side of their
      illness in such a way that they can feel understood and respected. In this paper
      we describe a simple innovative art therapy intervention that we have developed
      within the Art Therapy Service in the Psychiatric Department of Memorial Sloan
      Kettering Cancer Center. METHOD: The patients work with a Body Outline as a
      starting template, together with the art therapist, in sessions lasting
      approximately 45 minutes. They are encouraged to fill the space inside and
      outside the Body Outline. They can use colored pastels, markers, or watercolor or
      cut out images for a collage. RESULTS: Seventy hospitalized adult cancer
      patients, 60 women and 10 men, used this intervention between January 1999 and
      May 2000. We have analyzed the variety of responses from the 70 patients, and
      three main groups have emerged, which have focused on the following issues: (1)
      visualization of physical pain, (2) communication of emotions, and (3) search for
      meaning/spirituality. SIGNIFICANCE OF RESULTS: The results suggest that because
      of its abstract symbolic feature, the Body Outline is a very flexible therapeutic
      intervention. It must be offered within the relationship with the art therapist,
      and it may fulfill quite a variety of expressive needs, from the description of
      physical pain to the elaboration of spiritual longings.

PMID- 16594276
TI  - A pilot study to examine the relationship between boredom and spirituality in
      cancer patients.
AB  - OBJECTIVE: Spirituality has been neglected when assessing the well-being of
      cancer patients. Traditionally, researchers have focused on areas such as
      physical, social, and emotional functioning. However, there is a potential for
      spirituality to have a large impact on quality of life in patients with cancer.
      The current study was conducted to investigate the relationship between
      spirituality and boredom, constraint, social contact, and depression. METHODS: A
      total of 100 oncology patients completed several assessment instruments,
      including the Purposelessness, Under-stimulation, and Boredom (PUB) Scale,
      Functional Assessment of Cancer Therapy Scale-Anemia, Brief Zung Self-Rating
      Depression Scale (BZSDS), Cancer Behavior Inventory, Systems of Belief Inventory,
      and Eastern Cooperative Oncology Group Performance Status Scale. RESULTS: The
      average age of the sample was 62.37 years (SD = 13.43) and was comprised of 60
      women (60%) and 40 men (40%). A regression analysis conducted to explore the
      impact of the variables on quality of life found only the BZSDS (R2 delta = .650,
      F = 180.392, p < .001) and the PUB Scale (R2 delta = .077, F = 26.885, p < .001)
      were significant predictors of quality of life. Another set of regression
      analyses were conducted to explore whether spirituality had a mediating effect on
      this relationship, but the mediated model was not supported. SIGNIFICANCE OF
      RESULTS: We conclude that spirituality and boredom are difficult concepts to
      define, operationalize, and measure, but crucial to our understanding of quality
      of life in advanced cancer. More research is needed to clarify the nature of the
      interrelationships between these important concepts.

PMID- 16594277
TI  - "Because you know there's an end to it": caring for a relative or friend with
      advanced breast cancer.
AB  - OBJECTIVE: The aim of this paper is to delineate the particular nature of the end
      of-life care experience from the perspective of family members and friends. Ideas
      drawn from feminist analyses of caring and the sociology of death and dying are
      used to illuminate study respondents' accounts. METHODS: Qualitative study with
      people who cared for a family member or friend who died of breast cancer. Two
      interviews were conducted with each of 12 study participants, and one carer
      responded by letter to a series of questions drawn from the interview guide.
      Accounts were analyzed with reference to grounded theory methods. RESULTS: The
      analysis presented here suggests that anticipating the death of an ill relative
      or friend generates imperatives to care, imperatives that are both "felt" and
      linked to wider social structures and processes. The value assigned to closeness
      with the ill person can be seen to reflect cultural injunctions toward a "good
      death," and to shape informal carers' perceptions of their labor. Also discussed
      in this paper are the complex negotiations undertaken by relatives and friends,
      for the life and death of someone with advanced cancer. SIGNIFICANCE OF RESULTS:
      This paper offers insight into the social processes of caregiving, revealing how
      care may be shaped in particular ways by an awareness of approaching death.

PMID- 16594278
TI  - Family care giving for patients at life's end: report from the cultural
      variations study (CVAS).
AB  - OBJECTIVE: To investigate differences between African American and White family
      caregivers in self-reported health, use of social support and external resources,
      and emotional and financial strain in the context of their care of a family
      member with advanced cancer. METHODS: Sixty-nine patient-designated family
      caregivers of patients with advanced lung or colon cancer interviewed between
      December 1999 and July 2001. RESULTS: Most African American and White family
      caregivers were able to identify someone else who was helping them in the care of
      their family member. Few caregivers used outside resources (e.g., home-based
      medical care, meal delivery, pastoral care, outside social support visitor) to
      assist in the support and care of the patient. At baseline, White caregivers were
      more likely to agree that caregiving caused work adjustments, (p=.28, p=.02) and
      emotional difficulties (p=.32, p=.008) and that caregiving had been completely
      overwhelming (p=.19, p=.12) than were African American caregivers. At follow-up,
      among family caregivers of patients who had died, 44% reported having to quit
      work to provide personal care for the patient. Twenty-five percent of family
      caregivers reported using most or all of the family's saving in caring for the
      patient. SIGNIFICANCE OF RESULTS: Caregivers of patients at end of life
      experience substantial emotional and financial difficulties related to
      caregiving. Family caregiving is a private undertaking with little use of outside
      resources to mitigate the burden.

PMID- 16594279
TI  - Meaningfulness in palliative home care: an interview study of dying cancer
      patients' next of kin.
AB  - OBJECTIVE: An increasing number of patients are cared for at home and the
      presence of next of kin is often a prerequisite for successful home care. The aim
      of this study was to describe and interpret the construct of meaningfulness in
      next of kin of cancer patients who are in advanced palliative home care. METHODS:
      The perspective of Antonovsky's salutogenic framework of sense of coherence was
      applied in the analysis. Using a hermeneutic approach, 19 next of kin were
      interviewed (n=30 interviews) during ongoing palliative home care. RESULTS:
      Elements that facilitated meaningfulness included comfort, retaining everyday
      life, action, commitment, and hope, which were of great importance for creating a
      perception of self-transcendence and that the best possible was done.
      SIGNIFICANCE OF RESULTS: The findings are discussed in relation to the concepts
      of meaning-based coping, tragic optimism, and existentialism. Clinical
      implications are suggested.

PMID- 16594280
TI  - Psychological and psychiatric aspects of palliative care: an annotated
      bibliography.
AB  - Articles from the last decade that have propelled the field of palliative care
      are reviewed. The areas of depression, anxiety, substance abuse, delirium, and
      grief are represented by seminal articles that define, explore, or thoroughly
      review these topics.

PMID- 16594281
TI  - A tool box for living: cancer reflections.

PMID- 16594282
TI  - Directions in research on spiritual and religious isues for imprroving palliative
      care.

PMID- 16594283
TI  - A systematic review of spiritual and religious variables in Palliative Medicine,
      American Journal of Hospice and Palliative Care, Hospice Journal, Journal of
      Palliative Care, and Journal of Pain and Symptom Management.
AB  - OBJECTIVE: There has been increasing recognition and acceptance of the importance
      of addressing existential and spiritual suffering as an important and necessary
      component of palliative medicine and end-of-life care in the United States. This
      paper seeks to. empirically and systematically examine the extent to which there
      is an adequate scientific research base on spirituality and its role in
      palliative care, in the palliative care and hospice literature. METHODS: We
      sought to locate all empirical studies published in five palliative
      medicine/hospice journals from 1994 to 1998. The journals included: American
      Journal of Hospice and Palliative Care, Journal of Palliative Care, Hospice
      Journal, Palliative Medicine, and The Journal of Pain and Symptom Management.
      Journal contents were searched to identify studies that included spiritual or
      religious measures or results. Case studies, editorials, and theoretical or
      descriptive articles were not included in the search. RESULTS: During the years
      1994-1998, 1,117 original empirical articles were published in the five journals
      reviewed. Only 6.3% (70 articles) included spiritual or religious variables. This
      percentage, while low, was better that the 1% previously reported in an
      examination of studies published in Journal of the American Medical Association,
      The Lancet, and New England Journal of Medicine. SIGNIFICANCE OF RESULTS: While
      researchers in the field of palliative care have studied spiritual/religious
      variables more than other areas of medicine, the total percentage for studies is
      still a low 6.3%. To move the field of palliative medicine forward so appropriate
      guidelines for spiritual care can be developed, it is critical that good research
      be conducted upon which to base spiritual care in an evidence-based model.
      Recommendations are made for future studies on spiritual care in palliative
      medicine.

PMID- 16594284
TI  - Spiritual pain and its care in patients with terminal cancer: construction of a
      conceptual framework by philosophical approach.
AB  - OBJECTIVE: In discussing spiritual care of patients with terminal cancer, it is
      important to clarify the structure of spiritual pain to be evaluated. METHODS: In
      this article, spiritual pain is defined as "pain caused by extinction of the
      being and the meaning of the self," and its structure was evaluated according to
      the three dimensions of the human being, that is, a being founded on temporality,
      a being in relationship, and a being with autonomy. RESULTS: As a result,
      spiritual pain of patients with terminal cancer could be described as
      meaninglessness of life, loss of identity, and worthlessness of living derived
      from loss of the future, loss of others, and loss of autonomy of a dying
      individual. SIGNIFICANCE OF RESULTS: On the basis of these understandings, the
      author deduced principles of spiritual care of terminally ill cancer patients as
      recovery of the future beyond death, others beyond death, and autonomy toward
      death in each dimension of the human being.

PMID- 16594285
TI  - Living in the face of death: interviews with 12 terminally ill women on home
      hospice care.
AB  - OBJECTIVE: To determine how home hospice patients deal with their impending death
      and whether there is a need for greater involvement of mental health
      professionals in the care of patients dying at home. METHOD: In a pilot study, 12
      female home hospice patients with advanced cancer and a median survival time of
      42 days were assessed using structured interviews and brief questionnaires.
      Topics of inquiry included facing death, fear of death, pain, fatigue,
      depression, and anxiety. Three key themes were extracted from the information
      reported by the women: (1) confronting the issue of death, (2) fear of dying and
      death and its correlates, and (3) spirituality/religious faith and its role in
      mitigating fear of death. RESULTS: First, all subjects reported thinking about
      their approaching death. For half of them, this thought was bothersome and these
      women were frequently troubled by unresolved issues and higher anxiety, pain, and
      fatigue. The majority of the subjects expressed a desire to actively discuss
      their impending death. Second, more than half of the patients reported being
      afraid of death and high death anxiety was associated with fear of dying in pain,
      high peak or usual pain, unresolved issues, and difficulty in parting with family
      in death. Third, most subjects experienced their religious faith as an important
      source of comfort and strength. SIGNIFICANCE OF RESULTS: A substantial subgroup
      of home hospice patients expressed problems dealing with their approaching death.
      These problems are amenable to psychological treatment, such as fear of death,
      unresolved issues, parting with family, and pain. The findings, thus, highlight
      the need for close collaboration of mental health professionals with home hospice
      institutions.

PMID- 16594286
TI  - A comparison of patients dying at home and patients dying at a hospice:
      sociodemographic factors and caregivers' experiences.
AB  - OBJECTIVE: The aim of this study was to investigate whether there were any
      differences between patients who died at home and patients who died at a hospice,
      that is, sociodemographic variables, the family caregivers' experiences of
      burden, and their opinion of reasons for hospice care. METHODS: The study
      comprises a consecutive sample of family caregivers to adult patients: (I) who
      were cared for by the advanced palliative home care team (APHCT) and died at
      home, (II) who were cared for by the APHCT and died at the Hospice, (III) who
      were cared for and died at the Hospice in Uppsala during a period of one year. A
      questionnaire was mailed to caregivers and the medical records of all the
      patients were analyzed. RESULTS: The place of death differed significantly and
      varied according to gender and cohabitation status. Men died to a greater degree
      at home compared with women. The family caregivers' experiences of burden were
      moderate. Caregivers of patients who died at home thought that this care form has
      a more positive influence on the patients' quality of life than was the case in
      the other groups. They were also more satisfied with their own achievement. The
      caregivers' opinion of why patients needed hospice care was nearly the same in
      groups II + III, acutely developing symptoms being the most common reason.
      SIGNIFICANCE OF RESULTS: This study showed that women died to a lesser degree at
      home than men. The explanation for this is unknown and requires further
      investigation. It is important to establish whether female patients or male
      caregivers need another type of support than male patients or female caregivers,
      since the aim of palliative care is that every patient who wishes to die at home
      should have this wish fulfilled.

PMID- 16594287
TI  - Initial validation of a scale to measure purposelessness, understimulation, and
      boredom in cancer patients: toward a redefinition of depression in advanced
      disease.
AB  - OBJECTIVE: The problem of boredom in people with cancer has received little
      research attention, and yet clinical experience suggests that it has the
      potential to profoundly affect quality of life in those patients. We were
      interested in developing a Purposelessness, Understimulation, and Boredom (PUB)
      Scale to identify this problem and to begin to differentiate it from depression.
      METHODS: Cancer patients and professionals were interviewed using a semi
      structured format to elicit their perceptions of the incidence, causes, scope,
      and consequences of boredom. From their responses, 45 questions were developed,
      edited for clarity, and piloted. A total of 100 cancer patients were recruited to
      participate in the study. Preliminary validation of the PUB using a cross
      sectional survey of the measure was conducted. Other instruments used for
      purposes of convergent and divergent validity included the Functional Assessment
      of Cancer Therapy Scale-Anemia, Zung Self-Rating Depression Scale, Boredom
      Proneness Scale, Leisure Boredom Scale, Cancer Behavior Inventory, Systems of
      Belief Inventory, and the Eastern Cooperative Oncology Group Performance Status
      Scale. RESULTS: The average age of the sample was 62.37 years (SD = 13.43) and
      was comprised of 60 women (60.00%) and 40 men (40.00%). The results of a factor
      analysis on the 45 initial items (selected on the basis of professional and
      patient interviews) created a two-factor scale. The eight items from the
      strongest factor (items 1, 2, 3, 4, 5, 6, 9, 10) seemed to best tap the construct
      that could be deemed as overt boredom whereas the six items of the second factor
      (items 36, 38, 39, 42, 44, 45) seemed to tap the construct of boredom related to
      meaning and spirituality. Total scale internal consistency, when all 14 items
      were included in the analysis, yielded a coefficient alpha of 0.84 and good test
      retest reliability at 2 weeks (r = .80, p < .001). The novel 14-item PUB Scale
      was significantly correlated to other measures of boredom; the Boredom Proneness
      Scale (r = -.588, p < .001) and the Leisure Boredom Scale (r = .576, p < .001).
      SIGNIFICANCE OF RESULTS: The PUB Scale was found to be a statistically viable
      tool with the ability to detect boredom and differentiate it from depression. In
      many respects this work is in concert with much of the current research and
      clinical effort going on in psycho-oncology that defines components of distress
      that in sum, redefines depression in advanced cancer.

PMID- 16594288
TI  - Should symptoms be scaled for intensity, frequency, or both?
AB  - OBJECTIVE: This study evaluated the comparability of two 5-point symptom self
      report rating scales: Intensity (from "not at all" to "very much") and Frequency
      (from "none of the time" to "all of the time"). Questions from the Functional
      Assessment of Chronic Illness Therapy (FACIT)-Fatigue 13-item scale was examined.
      METHODS: Data from 161 patients (60 cancer, 51 stroke, 50 HIV) were calibrated
      separately to fit an item response theory-based rating scale model (RSM). The RSM
      specifies intersection parameters (step thresholds) between two adjacent response
      categories and the item location parameter that reflects the probability that a
      problem will be endorsed. Along with patient fatigue scores ("measures"), the
      spread of the step thresholds and between-threshold ranges were examined. The
      item locations were also examined for differential item functioning. RESULTS:
      There was no mean raw score difference between intensity and frequency rating
      scales (37.2 vs. 36.4, p = n.s.). The high correlation (r = .86, p < .001)
      between the intensity versus frequency scores indicated their essential
      equivalence. However, frequency step thresholds covered more of the fatigue
      measurement continuum and were more equidistant, and therefore reduced floor and
      ceiling effects. SIGNIFICANCE OF RESULTS: These two scaling methods produce
      essentially equivalent fatigue estimates; it is difficult to justify assessing
      both. The frequency response scaling may be preferable in that it provides fuller
      coverage of the fatigue continuum, including slightly better differentiation of
      people with relatively little fatigue, and a small group of the most fatigued
      patients. Intensity response scaling offers slightly more precision among the
      patients with significant fatigue.

PMID- 16594289
TI  - Mental adjustment after surgery for non-small cell lung cancer.
AB  - OBJECTIVE: Although surgery for early-stage non-small cell lung cancer (NSCLC) is
      generally considered curative, the outcome is still unsatisfactory, leaving
      patients faced with uncertainty and fear of recurrence for a long time after
      surgery. The purpose of this study was to clarify the course of patients' mental
      adjustment after surgery for NSCLC and to identify predictors of long-term
      outcome. METHODS: A total of 205 patients completed a baseline interview for
      patient characteristics at 1 month after curative resection of NSCLC and for
      social support at 3 months, and the Mental Adjustment to Cancer scale at 3 and 12
      months. Univariate and multivariate analyses were used to identify predictors of
      their psychological outcome. RESULTS: The helplessness/hopelessness subscale
      score improved slightly after curative resection (p < .001), but the score on the
      fighting spirit subscale score was unchanged (p = .659). Significant predictors
      of helplessness/hopelessness at 12 months included helplessness/hopelessness at 3
      months and advanced disease stage, and satisfaction with confidants. Significant
      predictors of fighting spirit at 12 months included fighting spirit at 3 months
      existence of confidants. SIGNIFICANCE OF RESULTS: The results suggested that
      mental adjustment improved slightly after curative resection for NSCLC. They also
      suggested the need to maintain continuity of psychosocial care that provides
      social support, and that an approach that includes careful attention to patients
      with advanced stage disease may be a strategy for improving mental adjustment
      after surgery for NSCLC.

PMID- 16594290
TI  - An open label pilot study of citalopram for depression and boredom in ambulatory
      cancer patients.
AB  - OBJECTIVE: Significant levels of depressive symptoms are an impediment to
      adjustment and affect greater than one-third of people with cancer. The clinical
      diagnosis of major depression is estimated to occur in 25%. Depression is
      dramatically underrecognized by oncologists and oncology nurses, and as a result,
      often undertreated. Clinical experience suggests that antidepressants of
      virtually all types are well tolerated and potentially efficacious. There is,
      however, a lack of an evidence base for the use of antidepressants in cancer
      patients. METHODS: We undertook an open-label pilot study using citalopram in 30
      cancer patients who reported a high level of depressive symptoms on the Zung Self
      Rating Depression Scale (ZSDS). In addition to the ZSDS, eligible patients
      completed a series of visual analog scales for pain, depression, and sleep
      disturbance; the Functional Assessment of Cancer Therapy-General Module; and the
      Purposelessness, Understimulation, and Boredom Scale developed by the research
      team. Patients began a 2-month course of therapy with citalopram 20 mg,
      increasing to 40 mg at the end of the fourth week if the patient was in the same
      range of depressive symptoms as measured by the ZSDS. RESULTS: Twenty-one of 30
      patients completed the protocol. The average age of the sample was 57.32 years
      (SD = 12.6) and was comprised of 11 women (52.4%) and 10 men (47.6%). Depressive
      symptoms decreased and quality of life improved during the 8-week treatment
      period. Of special interest was the rate of improvement in boredom, and using the
      total boredom score of the PUB, significant improvement compared to baseline was
      seen in weeks 6 (F = 5.266, p < .05) and 8 (F = 9.248, p < .01). SIGNIFICANCE OF
      RESULTS: Overall, the positive findings suggest the need for a randomized, double
      blind, placebo-controlled trial of citalopram in cancer patients. Regarding the
      interplay of boredom and depression, the relationship between improvements in
      depressive symptoms and boredom is complex. This is illustrated by the way in
      which the different elements respond to antidepressant treatment. Depression
      began to improve almost immediately upon initiation of treatment whereas
      improvement in boredom does not become evident until week 6.

PMID- 16594291
TI  - An ethical dilemma in a hospice setting.
AB  - The codes of ethics of the National Hospice and Palliative Care Organization and
      the National Association of Social Workers support ethical standards of client
      self-determination and confidentiality. Lack of societal consensus on the
      parameters of a terminally ill person's right to die continues to confound at
      times the health care field, including hospice programs. This article explores an
      actual case where a hospice social worker faced an ethical dilemma related to the
      sanctity of life versus patient autonomy. While a more seasoned social worker
      might have chosen a different alternative to the dilemma, this case illustrates
      the importance of creating an interdisciplinary rather than multidisciplinary
      hospice team and the need for ongoing dialogue on how to support patient choice.

PMID- 16594292
TI  - A psychiatrist in hospice.

PMID- 16594293
TI  - The existential moment.

PMID- 16594294
TI  - Resistor mesh model of a spherical head: part 1: applications to scalp potential
      interpolation.
AB  - A resistor mesh model (RMM) has been implemented to describe the electrical
      properties of the head and the configuration of the intracerebral current sources
      by simulation of forward and inverse problems in electroencephalogram/event
      related potential (EEG/ERP) studies. For this study, the RMM representing the
      three basic tissues of the human head (brain, skull and scalp) was superimposed
      on a spherical volume mimicking the head volume: it included 43 102 resistances
      and 14 123 nodes. The validation was performed with reference to the analytical
      model by consideration of a set of four dipoles close to the cortex. Using the
      RMM and the chosen dipoles, four distinct families of interpolation technique
      (nearest neighbour, polynomial, splines and lead fields) were tested and compared
      so that the scalp potentials could be recovered from the electrode potentials.
      The 3D spline interpolation and the inverse forward technique (IFT) gave the best
      results. The IFT is very easy to use when the lead-field matrix between scalp
      electrodes and cortex nodes has been calculated. By simple application of the
      Moore-Penrose pseudo inverse matrix to the electrode cap potentials, a set of
      current sources on the cortex is obtained. Then, the forward problem using these
      cortex sources renders all the scalp potentials.

PMID- 16594295
TI  - Resistor mesh model of a spherical head: part 2: a review of applications to
      cortical mapping.
AB  - A resistor mesh model (RMM) has been validated with reference to the analytical
      model by consideration of a set of four dipoles close to the cortex. The
      application of the RMM to scalp potential interpolation was detailed in Part 1.
      Using the RMM and the same four dipoles, the different methods of cortical
      mapping were compared and have shown the potentiality of this RMM for obtaining
      current and potential cortical distributions. The lead-field matrices are well
      adapted tools, but the use of a square matrix of high dimension does not permit
      the inverse solution to be improved in the presence of noise, as a regularisation
      technique is necessary with noisy data. With the RMM, the transfer matrix and the
      cortical imaging technique proved to be easy to implement. Further development of
      the RMM will include application to more realistic head models with more accurate
      conductivities.

PMID- 16594296
TI  - Spatiotemporal evaluation of human colon motility using three-axis fluxgates and
      magnetic markers.
AB  - An alternative method to study the mechanical activity of the human colon in
      fasting and postprandial states is presented. The method is based on measurements
      of the magnetic fields produced by a magnetic marker, a small cylindrical NdBFe
      magnet, when it was ingested by the subjects. A portable magnetic probe,
      consisting of two digital three-axis fluxgate magnetometers, arranged in a first
      order electronic gradiometer, was implemented for this research. Measurements
      were taken in 16 healthy male subjects. Contractile activity frequency
      measurements were taken along the colon length, including the ascending,
      transverse and descending sections, as well as the rectal sigmoidal section.
      Values for the contractile activity frequency of 2-5 cycles min(-1) were
      measured. The set-up is simple, low-cost and suitable for use in an unshielded
      environment.

PMID- 16594298
TI  - Simple two-electrode biosignal amplifier.
AB  - A simple, cost effective circuit for a two-electrode non-differential
      biopotential amplifier is proposed. It uses a 'virtual ground' transimpedance
      amplifier and a parallel RC network for input common mode current equalisation,
      while the signal input impedance preserves its high value. With this innovative
      interface circuit, a simple non-inverting amplifier fully emulates high CMRR
      differential. The amplifier equivalent CMRR (typical range from 70-100 dB) is
      equal to the open loop gain of the operational amplifier used in the
      transimpedance interface stage. The circuit has very simple structure and
      utilises a small number of popular components. The amplifier is intended for use
      in various two-electrode applications, such as Holter-type monitors,
      defibrillators, ECG monitors, biotelemetry devices etc.

PMID- 16594297
TI  - Unconstrained cardiorespiratory and body movement monitoring system for home
      care.
AB  - An unconstrained respiratory rate (RR) and heart rate (HR) monitoring system to
      be used during sleeping is proposed. The system consisted of eight polyvinylidene
      fluoride cable sensors, charge amplifiers and measuring software, together with
      an analogue-to-digital converter unit. The cable sensors were horizontally
      embedded into a textile sheet on a bed surface covering the upper half of the
      body. The digital infinite impulse response filters were constructed to extract
      cardiorespiratory signals from displacement of the sensors. The system software
      automatically searched the optimum sensor(s) based on the power of the respective
      filter outputs. Then, the system obtained the 5 s average HR and 15 s average RR
      by measuring the intervals between the peaks of the respective autocorrelation
      functions of the filtered output. If the subject changed his posture, the system
      captured the image of the body position as a time stamp using a CCD camera. To
      show the validity of this method, the HR and RR obtained by this monitor were
      compared with those simultaneously measured using respiratory flow and an
      electrocardiogram. The results showed that the mean frame-by-frame difference
      ranged from -1.2 to 0.2 beats min(-1) for the HR and, for RR, ranged from -0.8 to
      1.4 breath min(-1) during the short-term recordings. Similar differences were
      obtained during the first 2 h of overnight recordings. The proposed system is
      feasible for the combined long-term monitoring of a person's RR and HR with sleep
      posture changes and may be helpful for practical use in the home.

PMID- 16594299
TI  - Blood lines conduct leakage current during haemodialysis: a potential safety risk
      during first failure, especially for patients with central dialysis catheter as
      access.
AB  - Haemodialysis (HD) machines are IEC-classified as I type B. When central dialysis
      catheters (CDCs) are used for access, there will be close electrical contact with
      the heart. To investigate the risk for HD patients, the leakage of current
      through the tubing set was measured during in vitro dialysis performed according
      to the IEC 60601-1 standard for class I cardiac floating (CF) devices. A series
      of eight measurements were made with Gambro GFS + 12 dialysers, first with saline
      and then with blood in the blood lines. The leakage current exceeded the CF limit
      (50 microA) at the top of the CDC using the test 'mains on applied part' for
      saline (median 1008 microA, range 720-1241 microA), for blood (median 610 microA,
      range 449-772 microA) and also for a 'single fault condition' using saline
      (median 68 microA, range 35-118 microA) or blood (47 microA, range 4-128 microA).
      In the single fault condition, the highest leakage current at the CDC (128
      microA) almost exceeded the earth leakage current in normal conditions. A safety
      risk can appear if a single fault arises in the dialysis machine or another
      device connected to the same patient, or during 'mains contact to the patient'.
      Then the current flow may be high enough to induce arrhythmias in the patient,
      especially when a CDC is used. These data and the use of CDCs as access for
      dialysis indicate that HD machines should be classified as cardiac floating
      rather than body (B) devices.

PMID- 16594300
TI  - Industrial wideband noise reduction for hearing aids using a headset with
      adaptive-feedback active noise cancellation.
AB  - High-intensity noises are a health hazard for industrial workers, and hearing
      protection is necessary to prevent hearing loss. Passive methods, such as ear
      muffs, are ineffective against low-frequency noise. Moreover, many hearing
      impaired workers must wear hearing aids to enable communication at their
      workplace, and such aids can amplify ambient noise. To overcome this problem, the
      present study developed a headset equipped with a digital signal processing
      system to implement adaptive-feedback active noise cancellation (AFANC) to reduce
      low-frequency noise. The proposed AFANC headset was effective against wideband
      industrial noise, with a maximum noise spectrum power reduction of 30 dB.
      Furthermore, when used with a hearing aid, it improved the speech signal-to-noise
      ratio by up to 14 dB. These results suggest that a headset with AFANC would be
      useful for hearing protection in workplaces with high levels of low-frequency
      industrial noise, especially for hearing-impaired workers.

PMID- 16594301
TI  - Smart orthosis for the treatment of adolescent idiopathic scoliosis.
AB  - There is considerable controversy regarding the effectiveness of orthotic
      treatment for patients with adolescent idiopathic scoliosis. Most researchers
      believe that, to be effective, the orthosis must be worn as prescribed for both
      compliance and tightness. Compliance is the time the brace is worn relative to
      the prescribed time. A battery-powered microcomputer system was developed to
      monitor and maintain the loads exerted by orthoses used to treat children with
      spinal deformities during daily living. This system not only records how well and
      for how much time the brace has been used, but also helps patients to ensure that
      the brace is being worn at the prescribed tightness. Laboratory tests were
      performed, and five patients used the system for four weeks. The patients
      reported that the system helped them to wear the orthoses correctly and
      comfortably. The time that the patients wore the orthoses at the prescribed
      tightness level increased from 53 +/- 9% during the monitoring period (first 2
      weeks) to 68 +/- 14% during the automatic adjustment period (last 2 weeks).

PMID- 16594302
TI  - Microcontrolled pyro-electric instrument for measuring X-ray intensity in
      mammography.
AB  - A novel instrument for measurement of X-ray intensity from mammography consists
      of a sensitive pyro-electric detector, a high-sensitivity, low-noise current-to
      voltage converter, a microcontroller and a digital display. The heart of this
      device, and what makes it unique is the pyro-electric detector, which measures
      radiation by converting heat from absorbed incident X-rays into an electric
      current. This current is then converted to a voltage and digitised. The detector
      consists of a ferro-electric crystal; two types were tested: lithium tantalate
      and lithium niobate. X-ray measurement in mammography is challenging because of
      its relatively low photon energy range, from 11 keV to 15 keV equivalent mean
      energy, corresponding to a peak tube potential from 22 to 36 kV. Consequently,
      energy fluence rate or intensity is low compared with that of common diagnostic X
      ray. The instrument is capable of measuring intensities as low as 0.25 mW m(-2)
      with precision greater than 99%. Not only was the instrument capable of
      performing in the clinical environment, with high background electromagnetic
      interference and vibration, but its performance was not degraded after being
      subjected to 140 roentgen (3.6 x 10(-2) C kg(-2) air) as measured by piezo
      electric (d33) or pyro-electric coefficients.

PMID- 16594303
TI  - Texture analysis of foot sole soft tissue images in diabetic neuropathy using
      wavelet transform.
AB  - The paper presents a new method of characterisation of texture changes in foot
      sole soft tissue ultrasound (US) images, as observed to occur in diabetic
      subjects, using wavelet transforms. US images of the soft tissue subcutaneous
      layer were taken with a 7.5 MHz linear transducer probe placed parallel to the
      skin surface. The foot sole hardness was characterised by Shore level. A 2D
      discrete wavelet transform was performed on the US images to extract features
      that encode the internal state of the foot sole soft tissue. The global energy
      feature computed at the output of each wavelet channel was found to achieve
      excellent delineation between the normal and the diabetic groups. An important
      finding was a strong correlation, in the order of 0.84 and above, between the
      feature values that reflect changes in the internal arrangement of the tissue,
      and the externally measurable hardening of the skin, characterised by the Shore
      levels, with the latter known to be high for diabetics. A comparison drawn
      between diabetic ulcer and non-ulcer groups established a change in the order of
      122-311% in the textural parameter, as influenced by a corresponding 66.7-200%
      change in the respective Shore values. Thus US examination of foot sole soft
      tissue and its texture analysis may serve as sources of valuable information
      regarding the internal changes taking place with progressive hardening of the
      soft tissue and thereby help the clinician in taking appropriate preventive
      measures.

PMID- 16594304
TI  - Tracking and detection of epileptiform activity in multichannel ictal EEG using
      signal subspace correlation of seizure source scalp topographies.
AB  - Conventional methods for monitoring clinical (epileptiform) multichannel
      electroencephalogram (EEG) signals often involve morphological, spectral or time
      frequency analysis on individual channels to determine waveform features for
      detecting and classifying ictal events (seizures) and inter-ictal spikes. Blind
      source separation (BSS) methods, such as independent component analysis (ICA),
      are increasingly being used in biomedical signal processing and EEG analysis for
      extracting a set of underlying source waveforms and sensor projections from
      multivariate time-series data, some of which reflect clinically relevant
      neurophysiological (epileptiform) activity. The work presents an alternative
      spatial approach to source tracking and detection in multichannel EEG that
      exploits prior knowledge of the spatial topographies of the sensor projections
      associated with the target sources. The target source sensor projections are
      obtained by ICA decomposition of data segments containing representative examples
      of target source activity, e.g. a seizure or ocular artifact. Source tracking and
      detection are then based on the subspace correlation between individual target
      sensor projections and the signal subspace over a moving window. Different window
      lengths and subspace correlation threshold criteria reflect transient or
      sustained target source activity. To study the behaviour and potential
      application of this spatial source tracking and detection approach, the method
      was used to detect (transient) ocular artifacts and (sustained) seizure activity
      in two segments of 25-channel EEG data recorded from one epilepsy patient on two
      separate occasions, with promising and intuitive results.

PMID- 16594305
TI  - Influence of the time of occlusion on the quantitative parameters obtained by
      modelling trans-epidermal water loss curves to describe the human cutaneous
      barrier function in vivo.
AB  - Understanding the human cutaneous barrier function is one of the main goals in
      the study of skin physiology. The plastic occlusion stress test (POST) is a well
      known, dynamic approach for studying the barrier, evoking an over-stimulation of
      the cutaneous water assessed by the trans-epidermal water loss (TEWL)
      measurement. Rigorous data analysis is imperative, and the compartmental model
      proposed is particularly suitable for this purpose. It provides a dynamic
      quantitative description of water mass, but also helps to disclose the relative
      influence of other factors, such as the time of occlusion. Ten healthy volunteers
      were submitted to POST studies with different occlusion periods (1 h, 6 h, 12 h
      and 24 h), allowing the full application of the model to the measured desorption
      curves. After fitting, the influence of the occlusion time over the evaporation
      half-lives (t1/2evap) is apparent (t1/2evap ranging from 2.46 min for 1 h of
      occlusion to 8.53 min for 24 h), increasing with time. Considering the wide
      applicability of the POST to the study of in vivo cutaneous physiology and
      pathophysiology, these results demonstrate that the time of occlusion must be
      considered as a key factor in POST measurements.

PMID- 16594306
TI  - Modelling passive cardiac conductivity during ischaemia.
AB  - The results of a geometric model of cardiac tissue, used to compute the bidomain
      conductivity tensors during three phases of ischaemia, are described. Ischaemic
      conditions were simulated by model parameters being changed to match the
      morphological and electrical changes of three phases of ischaemia reported in
      literature. The simulated changes included collapse of the interstitial space,
      cell swelling and the closure of gap junctions. The model contained 64 myocytes
      described by 2 million tetrahedral elements, to which an external electric field
      was applied, and then the finite element method was used to compute the
      associated current density. In the first case, a reduction in the amount of
      interstitial space led to a reduction in extracellular longitudinal conductivity
      by about 20%, which is in the range of reported literature values. Moderate cell
      swelling in the order of 10-20% did not affect extracellular conductivity
      considerably. To match the reported drop in total tissue conductance reported in
      experimental studies during the third phase of ischaemia, a ten fold increase in
      the gap junction resistance was simulated. This ten-fold increase correlates well
      with the reported changes in gap junction densities in the literature.

PMID- 16594307
TI  - Influence of electrophysiological heterogeneity on electrical stimulation in
      healthy and failing human hearts.
AB  - The application of strong electrical stimuli is a common method used for
      terminating irregular cardiac behaviour. The study presents the influence of
      electrophysiological heterogeneity on the response of human hearts to electrical
      stimulation. The human electrophysiology was simulated using the ten Tusscher
      Noble-Noble-Panfilov cell model. The anisotropic propagation of depolarisation in
      three-dimensional virtual myocardial preparations was calculated using bidomain
      equations. The research was carried out on different types of virtual cardiac
      wedge. The selection of the modelling parameters emphasises the influence of
      cellular electrophysiology on the response of the human myocardium to electrical
      stimulation. The simulations were initially performed on a virtual cardiac
      control model characterised by electrophysiological homogeneity. The second
      preparation incorporated the transmural electrophysiological heterogeneity
      characteristic of the healthy human heart. In the third model type, the normal
      electrophysiological heterogeneity was modified by the conditions of heart
      failure. The main currents responsible for repolarisation (Ito, IKs and IKI) were
      reduced by 25%. Successively, [Na+]i was increased by the regulation of the Na+
      Ca2+ exchange function, and fibrosis was represented by decreasing electrical
      conductivity. Various electrical stimulation configurations were used to
      investigate the differences in the responses of the three different models.
      Monophasic and biphasic electrical stimuli were applied through rectangular
      paddles and needle electrodes. A whole systolic period was simulated. The
      distribution of the transmembrane voltage indicated that the modification of
      electrophysiological heterogeneity induced drastic changes during the
      repolarisation phase. The results illustrated that each of the heart failure
      conditions amplifies the modification of the response of the myocardium to
      electrical stimulation. Therefore a theoretical model of the failing human heart
      must incorporate all the characteristic features.

PMID- 16594308
TI  - Influence of peripheral chemodenervation on the complexity of respiratory
      patterns during early maturation.
AB  - Previous studies in humans have revealed that, during development, the
      fetus/neonate may be susceptible to environmental perturbations such as
      overheating, smoking, hypercapnia and hypoxia (LEWIS and BOSQUE, 1995; MASKERY,
      1995). In particular, alterations in behavioural states during early development
      can result in permanent alterations in their organisational states and subsequent
      abnormalities in the regulation of the cardiovascular and respiratory systems.
      The influence of the peripheral chemoreceptor afferent input on the approximate
      entropy (complexity) of the phrenic neurogram in the piglet was investigated in
      three different age groups: 3-7 days (n = 7), 10-16 days (n = 6) and 25-31 days
      (n = 4). The phrenic neurogram was recorded from piglets during control (40% O2)
      and severe hypoxia (gasping) (5-10% O2), before and after peripheral
      chemodenervation, and was analysed using the approximate entropy (ApEn) method.
      The results show that the complexity values of the phrenic neurogram during
      eupnea and gasping did not change significantly before and after
      chemodenervation, regardless of postnatal age. The complexity values during
      gasping were not significantly influenced by the carotid chemodenervation for the
      3-7 day-old group, but they were significantly decreased by the carotid
      chemodenervation for the 10-16 day-old age group (p < 0.01) and the 25-31 day-old
      age group (p < 0.05). However, the complexity values significantly decreased when
      the O2 concentration was shifted from eupnea to gasping (p < 0.001), both before
      and after the chemodenervation (p < 0.001), regardless of the postnatal age.
      These results suggest that the peripheral chemodenervation reduces the complexity
      of the phrenic neurograms during gasping only for the 10-16 day-old and 25-31 day
      old age groups, and it has no significant influence on the 3-7 day-old age group.
      Therefore it is speculated that the peripheral chemoreceptors may be inactive for
      the first seven days of postnatal life and become more active after seven days.

PMID- 16594309
TI  - Bactericidal effects of plasma-generated cluster ions.
AB  - Air purification by plasma-generated cluster ions (PCIs) relies on a novel
      technology producing hydrated positive and negative ions. Phenomenological tests
      have shown strong evidence of lethal effects of the PCIs on various micro
      organisms. However, the mechanisms of PCI action are still widely unknown. The
      aim was thus to test the bactericidal efficacy of PCI technology on common indoor
      micro-organisms and to explore possible PCI mechanisms of action. According to
      time/dose-dependent experiments with Staphylococcus, Enterococcus, Micrococcus
      and Bacillus, the inhibiting effects became apparent within the first few minutes
      of PCI exposure and led to an irreversible 99.9% destruction within the following
      2-8 h of exposure. The destructive effect of the PCIs corresponded to membrane
      damage of the bacteria. Use of the techniques of both SDS PAGE and 2D PAGE
      revealed changes in the bacterial surface protein composition induced by the
      PCIs. In contrast, neither DNA nor cytoplasm protein damage was detected
      electrophoretically. The antimicrobial action of the PCIs seems to occur because
      of chemical modification of the surface proteins of bacteria. In situ hydroxyl
      radical formation on the surface of bacteria was proposed as the leading
      mechanism of the protein damage caused by the PCIs. At the same time, DNA damage
      seems not to be involved in the antibacterial action of the PCIs. The data
      obtained would broaden the knowledge concerning the antibacterial effects of air
      born plasma-generated cluster ions and help to produce more efficient air
      cleaning devices.

PMID- 16594310
TI  - Is the physiotherapy profession under threat?

PMID- 16594311
TI  - Defining the Bobath concept using the Delphi technique.
AB  - BACKGROUND AND PURPOSE: The Bobath concept, based on the work of Berta and Karel
      Bobath, offers therapists working in the field of neurological rehabilitation a
      framework for their clinical interventions. It is the most commonly used approach
      in the UK. Although they recognize that over the last half-century the concept
      has undergone considerable developments, proponents of the Bobath concept have
      been criticized for not publishing these changes. The aim of the present study
      was to use the Delphi technique to enable experts in the field to define the
      current Bobath concept. METHOD: A four-round Delphi study design was used. The
      sample included all members of the British Bobath Tutor's Association, who are
      considered experts in the field. Initial statements were identified from the
      literature, with respondents generating additional statements during the study.
      The level of agreement was determined using a five-point Likert scale. The
      respondents were then provided with feedback on group opinions and given an
      opportunity to re-rate each statement. The level of group consensus was set at
      80%. RESULTS: Fifteen experts took part. The response rate was 85% in the first
      round, and 93% in each subsequent round. Ten statements from the literature were
      rated with a further 12 generated by the experts. Thirteen statements achieved
      consensus for agreement and seven for disagreement. CONCLUSIONS: The Delphi study
      was an effective research tool, maintaining anonymity of responses and exploring
      expert opinions on the Bobath concept. The experts stated that Bobath's work has
      been misunderstood if it is considered as the inhibition of spasticity and the
      facilitation of normal movement, as described in some literature. They agreed
      that the Bobath concept was developed by the Bobaths as a living concept,
      understanding that as therapists' knowledge base grows their view of treatment
      broadens.

PMID- 16594312
TI  - Physiotherapists' perceptions and use of medical imaging information in practice.
AB  - BACKGROUND AND PURPOSE: Physiotherapists must take responsibility for all aspects
      of patient care. Information from medical imaging studies can influence clinical
      decisions. The purpose of the present study was to gather information about
      physiotherapists' perceptions and use of medical imaging information in clinical
      practice. METHOD: A survey questionnaire was developed, validated and pilot
      tested. Subjects were randomly selected from a pool of licensed physiotherapists
      practising in four California Physical Therapy Association Districts. The survey
      was sent to 500 physiotherapists. Data gathered from the survey were transcribed
      to spreadsheets for analysis. RESULTS: One hundred and twenty participants
      completed and returned the survey. Information from radiographs was most
      frequently available, followed by MRI and CT scan information, respectively.
      Respondents reported more use of information from reports than from images.
      Respondents also indicated that it was important to be able to review medical
      imaging information (70%), that they use medical imaging information in their
      practice when it is available (83.4%), that physiotherapists have the necessary
      knowledge and skills to use this type of information (77.3%), and that medical
      imaging should be covered in entry-level educational programmes (84.2%).
      Respondents additionally indicated that medical imaging information could be used
      to understand a patient's disease process (85%), improve communication about
      patient care (90%), improve diagnosis, prognosis and interventions for patients
      (81.6%), and identify contraindications to examination and interventions (87.5%).
      CONCLUSIONS: Physiotherapists have access to some medical imaging information and
      perceive that this information could be valuable in patient care; however, not
      all therapists are confident in their ability to interpret this information.
      Curricula in entry-level physiotherapist educational programmes should include
      information about medical imaging.

PMID- 16594313
TI  - Goal attainment for spasticity management using botulinum toxin.
AB  - BACKGROUND AND PURPOSE: To determine whether goal attainment scaling (GAS) can
      demonstrate functional gains following injection of botulinum toxin (BTX) for
      spasticity in severely disabled patients. METHOD: Subjects were categorized as
      'responder' (positive clinical outcome) and 'non-responder' (non-significant
      clinical outcome) on the basis of their overall clinical response. GAS scores for
      functional goals were calculated retrospectively and compared with standard
      outcome assessments undertaken at the time of intervention. Integrated care
      pathway (ICP) proformas were interrogated for 18 patients with acquired brain
      injuries. Mean age was 44.4 (SD 13.4) years. RESULTS: Baseline GAS and Barthel
      scores were similar for the responder and non-responder groups. The outcome GAS
      score was significantly greater in the responder than in the non-responder group
      (Mann-Whitney U = 11.0; p = 0.011) as was the change in GAS score (Mann-Whitney U
      = 8.0; p = 0.004). GAS scores reflected change recorded in focal outcome
      measures. However, the Barthel Index measured change in only one case.
      CONCLUSIONS: This exploratory retrospective study provides preliminary support
      for the hypothesis that GAS provides a useful measure of functional gains in
      response to treatment with BTX, and is more sensitive than global measures such
      as the Barthel Index.

PMID- 16594314
TI  - Status of physiotherapy rehabilitation after total knee replacement in Australia.
AB  - BACKGROUND AND PURPOSE: Owing to a scarcity of clinical research, evidence-based
      clinical guidelines are not available to guide physiotherapy rehabilitation after
      total knee replacement surgery. This is despite the fact that, annually, over
      20000 patients in Australia, over 300 000 patients in North America and 36 000
      patients in the UK potentially require rehabilitation at this time to regain
      functional independence and to resume recreational and work-related physical
      activities. This survey of clinicians aimed to describe standard (usual) care
      after total knee replacement in Australia and to provide possible explanations
      for practice variance, if such variation exists. METHOD: A nationwide postal
      survey involving public and privately funded hospital physiotherapy departments
      was conducted. Purposive sampling was used to randomly select hospitals from the
      National Joint Replacement Registry. A series of closed and open-ended protocol
      based questions were asked. RESULTS: A response rate of 65% (65/100) was
      obtained. Elements of consistency and diversity across the acute and post-acute
      phases were evident. Consistent findings included the provision of gait
      retraining and exercise prescription in the acute period, the requirement for
      independent ambulation as a criterion for discharge from acute care and the
      routine referral to ongoing outpatient or community-based physiotherapy. Less
      consistency was reported for the use of continuous passive motion and cryotherapy
      in the acute phase, the modes of ongoing rehabilitation, discharge from
      rehabilitation criteria and the tools for measuring outcomes. Both institutional
      and non-institutional factors appeared to explain the demonstrated practice
      variation. CONCLUSIONS: In order to propagate evidence-based practice guidelines
      and uniformity in care, well-designed clinical trials are required to identify
      cost-effective rehabilitation programmes after total knee replacement.

PMID- 16594315
TI  - Short report: intra-tester reliability of two clinical tests of transversus
      abdominis muscle recruitment.

PMID- 16594316
TI  - Case report: activity after retirement.

PMID- 16594317
TI  - The origin of the term 'physiotherapy'.

PMID- 16594318
TI  - Management of agricultural nonpoint source pollution in China: current status and
      challenges.
AB  - Water quality in China shows an overall trend of deterioration in recent years.
      Nonpoint source pollution from agricultural and rural regions is the leading
      source of water pollution. The agricultural nonpoint source pollutants are mainly
      from fertilization of cropland, excessive livestock and poultry breeding and
      undefined disposal of daily living wastes in rural areas. Agricultural nonpoint
      sources contribute the main source of pollution to most watersheds in China, but
      they are ignored in management strategy and policy. Due to the lack of full
      understanding of water pollution control and management and the lack of perfect
      water quality standard systems and practical legislative regulations,
      agricultural nonpoint source pollution will become one of the biggest challenges
      to the sustainable development of rural areas and to society as a whole. The
      system for agricultural nonpoint source pollution control in China should include
      an appropriate legislation and policy framework, financing mechanisms, monitoring
      system, and technical guidelines and standards. The management of agricultural
      nonpoint source pollution requires multidisciplinary approaches that will involve
      a range of government departments, institutions and the public.

PMID- 16594319
TI  - Distribution of dioxins in surface soils and river-mouth sediments and their
      relevance to watershed properties.
AB  - The dioxins toxic equivalent (TEQ) concentration in surface soils, river
      sediments and river-mouth sediments was measured by the CALUX assay in the Yasu
      and Ado River basins around Lake Biwa, Japan. In order to examine the
      distribution of dioxins in each watershed, we evaluated and compared the
      correlation between the dioxins TEQ concentration and the solid characteristics
      (i.e. organic carbon content and particle size distribution) of all samples. In
      both basins, the dioxins TEQ concentration in forest soil correspondingly showed
      a very good linear relationship to organic carbon content. On the other hand, the
      dioxins TEQ concentration in paddy field was significantly high, although organic
      carbon content was relatively low. Generally, the smaller particles have the
      higher dioxins TEQ concentrations in surface soils, and river sediments were
      composed of very coarse particles and had relatively low dioxins TEQ
      concentration. Therefore, we expected high dioxins TEQ concentration in river
      mouth sediment, which was, however, not the case. Although the dioxins TEQ
      concentration in river-mouth sediments is low, the degree of dioxins pollution
      was different in each basin. The difference was considered to come from the
      difference of watershed properties including land use, river-slope, dam
      construction as well as the surface soil pollution.

PMID- 16594320
TI  - Study of water quality distribution in Lake Biwa in consideration of runoff
      pollutant loads from its catchment basin.
AB  - Many strategies for water quality conservation in Lake Biwa are being carried out
      mainly by reducing runoff pollutant loads into the lake. But influence of the
      runoff load reduction on the water quality in Lake Biwa has not been clarified
      enough so far. This study is aimed at discussing methodology to estimate water
      quality distribution in Lake Biwa using runoff pollutant loads from its basin.
      The runoff loads from the basin are calculated by Macro Model with GIS database
      of the Lake Biwa basin, and the water quality distribution in the lake is
      estimated by the spline technique with the calculated runoff loads. As a result,
      it has been proved that the methodology has enough reproducibility to estimate
      the water quality distribution in Lake Biwa and is available to examine the water
      quality in the lake.

PMID- 16594321
TI  - Estimation of annual pollutant loadings in two small catchments and examination
      of their differences caused by regional properties.
AB  - A series of runoff surveys was conducted for more than one year in two small
      catchments of the Kamo River basin (75.4 km2) and the Takano River basin (66.8
      km2) in Kyoto, Japan, which adjoin each other, and may have the same
      precipitation pattern. The investigation consisted of a high-frequency periodic
      survey, a long-term regular survey and a storm event survey. The survey results
      were compared with the regional properties of the basins, and the following
      results were obtained. (1) Pollutant loadings were successfully estimated as two
      portions of base discharge and storm events discharge from the survey results.
      (2) Estimated annual loading of the sites was 2.9-4.5, 1.3-1.8, 17-27, 1.3-2.2,
      0.076-0.97 t/km2/y, respectively for COD(Mn), DOC, SS, TN and TP. (3) 52-53% of
      the whole flow, which was caused by rainfall events, conveyed 81-87, 68-73, 92
      95, 64-67, 76-81% of the whole loading, respectively for COD(Mn), DOC, SS, TN and
      TP. (4) Differences of regional properties in two basins cause different runoff
      patterns, but the differences in runoff patterns also depend on the rainfall
      patterns. In general, a more urbanized basin receives early and strong influence
      of precipitation on the storm event runoff.

PMID- 16594322
TI  - Effects of soil erosion on water quality and water uses in the upper Phong
      watershed.
AB  - The main objective of this paper is to simulate the effects of soil erosion on
      river water quality and on agricultural production as a result of the
      transformation of forestlands in the catchment of the upstream Phong River.
      Suspended solids carry down attached nutrients and agricultural chemicals causing
      water pollution in the downstream. There are four different types of land use in
      this simulation, namely forestlands, flatland and highland sugarcane plantation
      areas, and paddy fields. The highest mean annual amount of soil erosion is from
      paddy fields (585,700 tons/year), followed by highland (73,800 tons/year) and
      flatland (63,950 tons/year) sugarcane plantation areas and forestlands (41,800
      tons/year), respectively. However, as most of paddy fields are located in a low
      land and are wet type cultivations, the soil erosion occurred has less impact on
      river water quality and its production compared to the soil erosion from the
      steeper slopes of highland plantation areas. Under the resource-based
      agriculture, the sugarcane production is mainly increased by expanding the
      plantation areas leading to a significant loss of topsoil and a considerable
      reduction of agricultural production. Soil erosion contributes to an increase in
      the average annual suspended solids concentration by 72 mg/l.

PMID- 16594323
TI  - Long-term fluctuation and regional variation of nutrient loads from the
      atmosphere to lakes.
AB  - The atmospheric depositions were collected by ordinary bulk-samplers mounted with
      a glass or polyethylene funnel of 30 cm orifice. A long-term observation was
      carried out at a site (35 degrees 01'30"N, 135 degrees 58'07"E) in the urbanized
      area for 21 years since 1974. The annual volume-weighted average concentrations
      of total nitrogen (TN) and phosphorus (TP) were 1.02 +/- 0.30 and 0.031 +/- 0.015
      mg(-1), respectively, and the loading rates were 14.5 +/- 2.8 and 0.43 +/- 0.16
      kg ha(-1) yr(-1). The rates neither had a relationship with the precipitation
      (1,492 +/- 343 mm yr(-1)) nor showed any diachronic tendencies. In order to
      obtain the loading rate of TN and TP within 10% uncertainty under the significant
      level of 0.01, there is no way but to continue the observation for seven and
      eleven years or more, respectively. In order to clarify the regional variation of
      the loading amounts of the depositions, the samplers were set at 12 sites
      distributing throughout the Kinki District for two years. The distance from
      northernmost (2322 mm yr(-1)) to southernmost (1242 mm yr(-1)) is about 150 km.
      The average loading rates of the 12 sites were 16.2 +/- 2.5 kg ha(-1) yr(-1) of
      TN and 0.730 +/- 0.247 kg ha(-1) yr(-1) of TP. The depositions of NO3-N, NH4-N,
      and TN as well as TP showed tendencies with distances neither from a big city nor
      from Japan Sea.

PMID- 16594324
TI  - Water chemistry gradient in a degraded bog area.
AB  - Surface and ground water was sampled in a degraded bog area 36 times during 1993 
      2003 at Five representative points: point E (natural area with Sphagnum as the
      main vegetal cover), point W (boundary between the natural and degraded areas),
      point W' (area installed with vinyl sheeting), point WW (area where Sasa
      thrives), and point NC (area with naturally formed ditches). Analysis of variance
      (ANOVA) was conducted for parameters measured in surface water and ground water
      at 0.5, 1.0, 1.5, and 2.0 m depths. "Sampling point" (i.e. locations along the
      degradation gradient) accounted for most of the variation in surface and ground
      water chemistry. It accounted for 30-80% of the total variation in pH, electrical
      conductivity, ammonia, dissolved nitrogen, major cations (Na+, K+, Ca2+, Mg2+),
      alkalinity and dissolved organic carbon. "Year" accounted for more variation in
      nitrate, nitrite, chloride, and sulfate than the sampling point did, but the
      variation in dissolved reactive phosphorus and dissolved phosphorus
      concentrations was not based on any of the calculated variables.

PMID- 16594325
TI  - Characteristics of sediments in a newly constructed reservoir in Japan.
AB  - The sediment formation mechanisms of a newly constructed reservoir in Ehime,
      Japan were evaluated by characterizing the soil particles (SP) and particulate
      phosphorus (PP) in the runoff and reservoir sediments. The SP and PP loads from
      the runoffs of the main river in the watershed considerably increased, when the
      specific discharge rates were over 300 l/s/km2 (high flow conditions). When the
      specific discharge rates exceeded over 300 l/s/km2, 19% of the watershed
      generated over 80% of the SP and PP loads. When the specific discharge rates were
      under 300 l/s/km2 (low flow conditions), the contributions of the previously
      mentioned 19% area to the SP and PP loads were smaller. Significant amounts of
      smectite were found in the sediments in the reservoir and in the soil samples
      obtained at the forest exposed area in this 19% area while it was negligible in
      citrus orchards and paddy fields that constituted the remaining land surfaces.
      The forest area exposed by recent landslides was significant for the SP and PP in
      the reservoir. Judging from the outcomes, land use information alone may not be
      sufficient to detect critical sources of SP and PP in the runoffs and reservoirs.
      To identify and confirm crucial areas for the SP and PP in the runoffs, the
      investigations should be conducted under high flow conditions and the composition
      of clay minerals in the sediments should be checked against the clay mineral
      distributions of soils in the watershed.

PMID- 16594326
TI  - Evaluation of nutrient loads from a mountain forest including storm runoff loads.
AB  - Water quality and flow rates at a weir installed on the end of Aburahi-S
      Experimental Watershed (3.34 ha) were measured once a week from 2001 to 2003 and
      in appropriate intervals from 30 min to 6 h during five storm runoff events
      caused by each rainfall from 8 mm to 417 mm. The average annual loads of total
      nitrogen (TN) and total phosphorus (TP) were calculated to be 19.0 and 0.339 kg
      ha(-1) y(-1) from the periodical data by using the integration interval-loads
      method (ILM), which did not properly account for storm runoff loads. Three types
      of L(Q) equations (L = aQ(b)) were derived from correlations between loading
      rates L and flow rates Q obtained from the periodic observation and from storm
      runoff observation. L(Q) equation method (LQM), which was derived from the storm
      runoff observation and allowed for the hysteresis of discharge of materials, gave
      9.68 and 0.159 kg ha(-1) y(-1), respectively, by substitution of the sequential
      hourly data of flow rates. L(R) equation (L = c(R - r)d) was derived from the
      correlations between the loads and the effective rainfall depth (R - r) measured
      during the storm runoff events, and L(R) equation method (LRM) calculated 9.83 +/
      1.68 and 0.175 +/- 0.0761 kg ha(-1) y(-1), respectively, by using the rainfall
      data for the past 16 years. The atmospheric input-fluxes of TN and TP were 16.5
      and 0.791 kg ha(-1) y(-1).

PMID- 16594327
TI  - Evaluation of hydrological processes in a mountainous small basin using a quinone
      biomarker.
AB  - An applicability of quinone biomarker to the analysis of hillslope runoff was
      investigated. At first, quinone profiles of three streams as well as a hillslope
      runoff in a forested headwater catchment were compared. The quinone composition
      of hillslope runoff differed from others. Moreover, there were remarkable
      differences in quinone profile of hillslope runoff under different rainfall
      conditions. Then, the behavior of quinone biomarker during the increase and
      decrease of hillslope runoff after a rainfall event was examined. The fractional
      changes in Q-9 (H2), Q-10 (H2), Q-11, MK-6 and MK-10 suggested the effect of
      interflow.

PMID- 16594328
TI  - Nitrogen removal function of recycling irrigation system.
AB  - The purpose of this study was to clarify the nitrogen (N) purification capacity
      of a paddy field in a recycling irrigation system. Irrigation water was sampled
      at 12-h intervals during the irrigation period from April to September 2003. In
      addition, ponded water in a paddy field was collected at three points (inlet,
      centre and outlet). Total amounts of N were 30.7 kg ha(-1) in inflow and 27.8 kg
      ha(-1) in outflow. Thus, the net outflow load was -2.9 kg ha(-1). The N removal
      rate constant when N removal is expressed as a 1st-order kinetic was 0.017-0.024
      m d(-1). This value is close to values of wetlands and paddy fields in the
      literature. We found a good correlation between recycling ratio and N removal
      effect. These results indicate that the recycling irrigation system accumulates N
      in the irrigation/drainage system, and thus the paddy field does a good job of
      water purification by removing N.

PMID- 16594329
TI  - Recycling mineral nutrients to farmland via compost application.
AB  - Increased cultivation of farmland has resulted in nutrient deficiency and
      consequently fertility degradation of soils. This research examined the
      application of composted wastes in terms of the feasibility and effectiveness of
      recycling plant essential minerals. Minerals in composts (derived from sewage
      sludge, livestock excrement, and municipal solid wastes, respectively) and in
      amended soils were observed. Ca/Mg ratios in amended soils and the effect of
      compost applications (mineral nutrients and heavy metals) on plant uptake were
      also studied. Results showed that composts, especially those made from sewage
      sludge and livestock excrement, were richer in mineral nutrients but also
      contained more heavy metals than untreated soil. The increase in some elements
      and plant-growth-essential Ca/Mg ratios were found in amended farmlands, implying
      that compost applications have made up for the nutrient deficiency and have
      adjusted chemical conditions of the soil. The soil contamination from heavy
      metals was noticeable. However, some results showed that the large existence of
      mineral nutrients and heavy metals in soils has caused no significant increase in
      the plant uptake of elements. The controlled composting process and farmland uses
      are believed necessary for reducing the heavy metal accumulation in agricultural
      plants.

PMID- 16594330
TI  - Study on the potential of farmland soils as non-point sources of nitrogen and
      phosphorus in Japan.
AB  - The amounts of N and P accumulated in farmland soils of 50 cm depth were
      equivalent to the amount of chemical fertilizer supplied for 50-70 years. The
      values of N/P of surface soils in farmlands were 1.0-4.3, lower than expected.
      The median diameter of soil particles in run-off waters was generally less than
      10 microm. The mean values of particulate fractions over 1 microm and over 0.22
      microm were 19% for N, 27% for P, and 39% for N, 64% for P respectively. Fine
      particles of soil containing concentrated phosphorus should be carefully
      monitored as potential sources related to eutrophication.

PMID- 16594331
TI  - Decrease in herbicide concentrations and affected factors in lagoons located
      around Lake Biwa.
AB  - The contamination levels and changes in the concentrations in four lagoons around
      Lake Biwa of paddy-use herbicide were studied. Four lagoons, Sone-numa (52 days
      of HRT (hydraulic residence time) estimated from the lagoon volume and the
      average discharge at the outlet, 21 ha area), Yanagihira-ko (40 days, 5.0 ha),
      Noda-numa (11 days, 6.0 ha), and Iba-naiko (2 days, 55.5 ha), were selected as
      monitoring sites. Intensive water sampling was carried out once a week from May
      to June at the outlet of each lagoon. Although twelve of the monitored herbicides
      were detected, the maximum concentrations did not exceed the guidelines for water
      supply law in Japan. The relation between half-lives in herbicide concentrations
      and characteristics of a lagoon such as HRT and chlorophyll-a concentrations were
      examined. The shorter half-lives of herbicide concentrations in lagoons with
      shorter HRT means that replacement by influent water effectively decreased the
      pesticide concentrations. Shorter half-lives in lagoons with high chlorophyll-a
      concentrations between the lagoons with similar HRT suggest that biological
      degradation during the residence time worked more efficiently in the lagoon with
      high chlorophyll-a concentrations.

PMID- 16594332
TI  - Estimation of pesticide runoff from paddy fields to rural rivers.
AB  - The runoff characteristics of pesticides from paddy fields to rural rivers were
      investigated over a period of three years in Hokkaido Prefecture, Japan. High
      pesticide concentrations were usually observed in rivers during pesticide
      application periods. In one year, the growth of rice seedlings slowed down after
      transplantation owing to low temperatures and lack of sunshine, and many farmers
      delayed herbicide application. In that year, high-concentration runoff of
      herbicides in rivers was observed 1-3 weeks later than in average years. The
      pesticide runoff rates ranged from 0.3% for fenthion to 42% for benfuresate. The
      runoff rates of pesticides applied post-flood were large. Furthermore, the larger
      the water solubility of the pesticide, the larger the runoff rate. The highest
      concentrations of herbicides in paddy water were observed on the day of
      application or 1-2 days later, and the concentrations decreased exponentially
      afterwards. The half-lives of the herbicides ranged from 1.2 days for
      pretilachlor and esprocarb to 5 days for simetryn; the concentrations of the
      herbicides in paddy water had decreased to 1/10 of their initial concentrations
      by about 7 days after application. Therefore, the runoff amounts of pesticides
      from paddy fields could be decreased by improving irrigation-water management.

PMID- 16594333
TI  - Economic valuation of reduction in nitrogen outflow from a paddy field area
      equipped with a recycling irrigation facility.
AB  - We estimated the reduction in nitrogen outflow load from a paddy field that had a
      recycling irrigation facility and, by using a replacement cost method, evaluated
      the economic effect of nitrogen removal by the paddy field during the irrigation
      period in the Yoshinuma region of Tsukuba City, Japan. The recycling ratio of
      outflow water (proportion of outflow reused) was 13.5%. The nitrogen (N) outflow
      load was reduced by about 45 kg ha(-1) by the N removal function of the paddy
      field and by about 39 kg ha(-1) by the recycling irrigation facility. The paddy
      field equipped with a recycling irrigation facility as an N removal facility was
      valued at 32.6 million Japanese yen (JPY) ha(-1) and 0.72 million JPY ha(-1) per
      year, which compare it with the construction and maintenance costs, respectively,
      of a water quality improvement facility. The recycling irrigation facility was
      costed at 17.3 million JPY ha(-1) for construction and 0.21 million JPY ha(-1)
      for maintenance per year. The cost for constructing and maintaining a recycling
      irrigation facility was 53% of the value of the paddy field area equipped with a
      recycling irrigation facility as an N removal facility.

PMID- 16594334
TI  - On-site treatment of turbid river water using chitosan, a natural organic polymer
      coagulant.
AB  - Chitosan, acetylate of chitin, is a biodegradable cationic polymer. The objective
      of this study is to assess the applicability of chitosan as an on-site treatment
      agent of turbid water caused by river construction works and other diffused
      pollutions. The results of jar-tests indicate that floc of chitosan is much
      larger than that of aluminium sulfate, and turbidity treated by chitosan under
      moving water conditions is much lower than that of aluminium sulfate. Chitosan is
      applied to Imou River in Yamaguchi prefecture, where river construction work is
      going on. St.1 is located just below the construction work, St.2 is located about
      250 m downstream from St.1, and St.3 is located about 350 m downstream from St.2.
      Initial turbidity of each station is 1,100, 937 and 313 NTU, respectively. By
      applying chitosan at St.1, turbidity of each station is drastically reduced to
      1,100, 12 and 0 NTU. Chitosan could be helpful to reduce problems caused by
      turbidity in rivers.

PMID- 16594335
TI  - Study on purification mechanism in soil penetration facility for effluents from
      urban area and control strategies.
AB  - In this study, demonstration experiments for removal of pollutants from road
      surface runoff during storm events were carried out under natural conditions in
      an outdoor pilot-scale soil penetration facility. In general, soil retains
      suspended matter and removes dissolved matter by adsorption. However, issues such
      as reduced purification capacity resulting from clogging and recovery of
      purification capacity during periods of intermittent supply of the storm water
      affect the removal efficiency of pollutants. Therefore, this study aimed at
      clarifying purification mechanisms during storm events and understanding how the
      structural characteristics of the soil penetration facility affect purification
      capacity based on long-term continuous measurements. In addition, modeling the
      purification mechanism under changing characteristics of rainfall in the long
      term was undertaken.

PMID- 16594336
TI  - Trace metal levels in sediments deposited in urban stormwater management
      facilities.
AB  - Characteristics of solids recovered from stormwater best management practice
      (BMP) facilities, including stormwater ponds, constructed wetlands, an
      infiltration basin, a biofilter, a stormwater treatment clarifier, and three
      chamber oil and grit separators were described with respect to their metal
      chemistry. The reported trace metal concentrations in BMP sediments were assessed
      against the Ontario Sediment Quality Guidelines. Between 80 to 100% of all
      samples were marginally-to-intermediately polluted by Cd, Cr, Cu, Fe, Pb, Mn, Ni
      and Zn. Severe pollution of sediments was noted for Cr (122 microg/g), Cu (151
      and 196 microg/g), Mn (1,259 and 1,433 microg/g), and Zn (1,116 microg/g), at
      several facilities studied, and even higher levels of metals were reported in the
      literature for certain oil and grit separators. With respect to individual BMPs,
      the severe pollution was found in sediments from oil and grit separators (for Cd,
      Cr, Cu, Pb and Zn), the stormwater clarifier sludge (Cu, Mn and Zn), a biofilter
      (Cu and Mn), an industrial area stormwater pond (Cu only), and a
      commercial/residential pond (Cr only). Finally, the chemical pollution of pond
      sediment triggered toxicity testing at some of the facilities studied, and
      sediment toxicity was confirmed at several sites.

PMID- 16594337
TI  - Lead isotope ratios in urban road runoff.
AB  - Lead isotopic analyses of road runoff and airborne particulate matter have been
      carried out to elucidate sources of lead pollution at urban and suburban sites.
      While lead is often observed in road runoff in suspended form, suspended particle
      size had no relation to the lead isotopic distribution, as a result of comparison
      between runoff samples with total suspended solids and those with minute
      particles passed through a 75 microm sieve. Lead isotope ratios in airborne
      particulate matter in urban areas fell within a wider range than those in road
      runoff. Since there was little difference of the ratios between a heavy traffic
      flow site and residential sites, airborne lead derived from vehicle exhaust was
      found to make little contribution to the contamination of road runoff. On the
      other hand, the ratios in road runoff at a suburban site showed the same range as
      those at an urban site. Lead in road runoff was therefore suggested to be
      produced on site by traffic related substances, such as tire wear, other than
      vehicle exhaust.

PMID- 16594338
TI  - The characteristics and measuring technique of refractory dissolved organic
      substances in urban runoff.
AB  - It is considered that refractory dissolved organic substances have caused an
      increase in the COD concentration in Lake Biwa in recent years. We investigated
      the organic matter in the first flush of stormwater runoff from a road in the
      watershed area of the lake, and studied the possibility of improvement in the
      water environment from that aspect. After percolating the stormwater through
      soil, we analyzed organic substances fractionated by using GPC-TC. And we
      examined the effect of removal of organic substances by comparing the peak height
      before and after percolation. In the result of the experiments, we found that
      soil infiltration reduced the refractory dissolved organic substance and we
      successfully designed a system for a simple and easy experimental facility to
      treat urban runoff.

PMID- 16594339
TI  - Runoff and loads of nutrients and heavy metals from an urbanized area.
AB  - To investigate the run-off characteristics of dissolved and particulate
      substances from a heavily urbanized area (basin area: 95 ha, percentage of
      impervious surfaces: 60%), sensors for measuring water level, water temperature,
      DO, pH, electric conductivity (EC), turbidity and ammonium ion were placed in the
      channel connecting storm sewers and natural river, together with water sampling
      for analyzing SS, nutrients and metals. While both turbidity and EC showed
      apparent "first flush", the peaks of EC were always earlier than those of
      turbidity. In a similar manner, dissolved nutrients and metals exhibited earlier
      "first flush" compared with particulate nutrients and acid-extractable metals.
      Significantly positive correlations between EC and dissolved substances as well
      as those between turbidity and particulate (acid-extractable minus dissolved)
      substances were usually observed, and two distinct different regressions were
      found between the two datasets separated before and after the concentration
      peaks. Using these relationships, the total loads during the respective rainfall
      events were calculated on the basis of EC and turbidity changes. The total loads
      of nitrogen, zinc, etc. were nearly proportional to the lengths of non-rainfall
      periods before the events, indicating that these loads derived from the
      atmospheric deposition.

PMID- 16594340
TI  - Dispersion and dry and wet deposition of PAHs in an atmospheric environment.
AB  - The atmospheric concentration and dry and wet deposition were measured for
      particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) from August
      to December in Higashi-Hiroshima City, Japan. PM concentration of fine particles
      (0.6-7 microm) was 5.7-75.1 micro m(-3), and coarse particles (> 7 microm) was
      2.2-22.3 microg m(-3). Total PAHs concentration of fine particles was 0.14-16.3
      ng m(-3), and coarse particles was 0.01-0.77 ng m(-3). Their concentration
      increased on non-rainy days and decreased rapidly on rainy days. For seasonal
      fluctuations of PAHs, their concentrations decreased from summer to winter, and
      the rate of decrease was more distinct for fine particles. For total (dry + wet)
      depositions, the PM flux was 1.9-11.2 mg m(-2) d(-1), and the total PAHs flux was
      1.9-97.2 ng m(-3) d(-1). From these measurements, the yearly total loading of
      PAHs was estimated for the particle phase. Total loading was 28 microg m(-2) y(
      1) for the dry deposition and 52 mg m(-2) y(-1) for the wet deposition. The
      loading of the wet deposition was comparable to those of the dry deposition for
      all ring numbers.

PMID- 16594341
TI  - Characteristics of litter waste in highway storm runoff.
AB  - Litter characterization is an integrated part of the Caltrans First Flush
      Characterization Study. These data will provide a basis to develop potential
      treatment technologies and best management practices to control pollutants in
      runoff from freeways. During monitoring periods in Southern California areas, the
      first flush phenomenon was evaluated and the impacts of various parameters such
      as rain intensity, drainage area, peak flow rate, and antecedent dry period on
      litter volume and loading rates were evaluated. First flush phenomenon was
      generally observed for litter concentrations, but was not apparent with litter
      mass loading rates. Total captured gross pollutants, defined as larger than 0.5
      cm, was 90% vegetation with only 10% being litter. The normalized cumulative
      litter loadings were determined from 1.25 to 13.39 kg/ha for dry litter weight
      and 0.40 to 8.99 kg/ha for dry biodegradable litter weight. The portions of
      biodegradable litter to non-biodegradable litter were roughly the same across the
      entire event. Event mean concentrations were ranged 0.0021 to 0.259 g/L for wet
      gross pollutants, 0.0001 to 0.027 g/L for wet litters and 0.00007 to 0.018 g/L
      for dry litters. The mass emission rates should be useful to estimate total
      litter production for developing total maximum daily loads.

PMID- 16594342
TI  - Correlation analysis among highway stormwater pollutants and characteristics.
AB  - Stormwater runoff from highway land use is a common non-point source of
      pollutants. A large quantity of highway stormwater runoff characteristics were
      collected in California during the past three years. Correlations among various
      water quality parameters and constituents were performed using data sets
      collected over the 2000-2001, 2001-2002, and 2002-2003 wet seasons for 18, 21 and
      23 storm events at three highway sites in west Los Angeles, California. In
      addition, statistical and graphical correlation analysis of the mass first flush
      ratio (MFF) with storm characteristics was made to determine if the first flush
      is related to site or storm characteristics. The results and analyses performed
      indicate that (1) TSS correlates well with most particulate-bound metals.
      However, TSS was poorly correlated with most other pollutants. (2) Strong
      correlations were also observed among dissolved and total metals; DOC, COD, TKN
      and oil and grease; conductivity and Cl. (3) Total metals, COD and DOC were
      generally well correlated with mass first flush, suggesting that BMPs that treat
      the early portion of runoff have an opportunity to remove high concentrations of
      these pollutants.

PMID- 16594343
TI  - Characteristics of particle-associated PAHs in a first flush of a highway runoff.
AB  - Runoff monitoring of six rainfall events was carried out in a highway,
      Winterthur, Switzerland focusing on first flush (runoff volume up to 2.88 mm).
      Six runoff events were used to investigate the characteristics of particle
      associated PAHs in first flush. The fine fraction (< 45 microm) had a relatively
      higher contribution than the coarse fraction. A significant contribution of the
      coarse fraction was observed at some periods when the runoff flow rapidly
      increased. Fluctuation of PAH content during a runoff event was significant in
      the coarse fraction and, in contrast, the PAH content in the fine fraction was
      less fluctuating. The weighted average PAH content in each event ranged from 17
      to 62 microg/g in total SS, from 23 to 54 microg/g in the fine fraction and from
      16 to 84 microg/g in the coarse fraction. The loading of particle-associated PAHs
      from the first flush of highway runoff ranged from 0.06 to 0.22 g/ha in a total
      of 12 PAH species.

PMID- 16594344
TI  - Water quality modeling to evaluate BMPs in rice paddies.
AB  - A water quality model applicable to rice paddies was developed using field data
      from 1999-2002. Use of the Dirac delta function efficiently explained the
      nutrient-concentration characteristics of ponded water. The model results agreed
      reasonably well with the observed data. The ponded-water quality was influenced
      primarily by fertilization; nutrient concentration was especially high during
      early cultivation periods. Reducing surface drainage during the fertilization
      period may substantially reduce nonpoint source loading from paddies. Increased
      weir heights and shallow irrigation methods were evaluated by the model as
      practical methods for reducing nutrient loading from paddies. These methods were
      effective in reducing surface drainage and are suggested as "best management
      practices" (BMPs) if applied based on site-specific paddy conditions.

PMID- 16594345
TI  - Evaluation of AnnAGNPS in cold and temperate regions.
AB  - Identification of the pollution sources and understanding the processes related
      to runoff generation and pollution transportation is effective for the water
      quality management and selection of the Best Management Practices. The ANNualized
      AGricultural Non-Point Source (AnnAGNPS) model was applied to a watershed in
      Southern Ontario to evaluate the hydrology and sediment component from the non
      point sources. The model was run for two years (1998 to 1999); one year's data
      was used to calibrate and the second year's data was used for validation
      purposes. The model has under predicted runoff amount and over predicted the
      sediment yield. However, the simulated runoff and sediment yield compared fairly
      well with the observed data indicating that the model had an acceptable
      performance in simulation of runoff and sediment. The study is still in progress
      to assess its performance for estimation of TMDL and improvements needed for the
      model to use under Ontario conditions.

PMID- 16594346
TI  - Nonlinear regression approach to evaluate nutrient delivery coefficient.
AB  - Implementation of the Korean Total Maximum Daily Load Act calls for new tools to
      quantify nutrient losses from diffuse sources at a river basin district scale. In
      this study, it was elucidated that the nonlinear regression model (NRM) reduces
      the uncertainty of the boundary conditions of the water quality model. The NRM
      was proposed to analyse the delivery coefficients of surface waters and retention
      coefficients of pollutants. Delivery coefficient of pollution load was considered
      as a function of two variables: the watershed form ratio, S(f), which is a
      measurable geomorphologic variable and the retention coefficient, phi, which is
      an empirical constant representing the basin-wide retarding capacity of pollutant
      wash-off. This model was applied on the Geum River, one of the major basins in
      South Korea. The QUAL2E was used to simulate stream water quality using NRM. In
      this paper, we elucidate the possibility to use a nonlinear regression model for
      delivery and retention of nutrients in a drainage basin characterized as both
      data-rich and data-poor, and the magnitude of the nutrient loads and sources has
      been uncertain for a long time.

PMID- 16594347
TI  - Comparative study of two watershed scale models to calculate diffuse phosphorus
      pollution.
AB  - The aim of this study was to compare and assess models having different
      principles to calculate diffuse phosphorus emissions on a selected watershed. The
      empirical MONERIS model and the physically based SWAT model were evaluated for
      comparative purposes. The approaches were applied for a sub-basin of the
      Hungarian Zala River watershed for five years. The calculated river loads were
      checked by the measured values at the catchment outlet. Due to the dissimilar
      results of water balance and erosion calculations, a highly different phosphorus
      emission was computed. It was also concluded that in the case of transport
      limited watersheds, the SWAT model calculates phosphorus river loads slightly
      inaccurately, since it does not include the description of fate of inorganic
      phosphorus interacting with sediment during the channel transport. When these
      processes are taken into account, modeling results fit better the measured loads.
      The MONERIS model calculates acceptable river load by assuming very intensive in
      stream retention. Additionally, the empirical method can be useful for long-term
      investigations as a decisions support tool for preliminary design. However, for
      detailed emission assessment and scenario development the physically based
      approach seems to be more appropriate.

PMID- 16594348
TI  - Integrating principles of nitrogen dynamics in a method to estimate leachable
      nitrogen under agricultural systems.
AB  - Surplus nitrogen (N) in ground and surface water is of concern in intensive
      agricultural regions. Surplus N leaches during lengthy periods where annual crop
      systems are used in temperate regions. This paper presents a model to estimate
      the surplus N available for leaching to ground water beneath agricultural systems
      and applies the model to watersheds in an intensive maize and soybean production
      system. The model utilizes commonly available georeferenced data on soils, crops,
      and livestock, making it applicable to watersheds in many regions. The model
      links stocks of N in soil, crops, livestock, fertilizer and the atmosphere.
      Nitrogen flow centers on exchange between the soil N stocks. Nitrogen
      mineralization rates are defined for three soil organic matter pools, crop
      residue, and manure based on carbon:N ratios. Nitrogen exports from the system
      are harvested crops, livestock and losses to the atmosphere. Application of the
      model in 26 Iowa watersheds finds surpluses of 18 to 43 kg-N/ha. Surpluses
      exceeded measured annual nitrate-N loads in regional streams by amounts
      equivalent to denitrification rates in groundwater. Deficits in soil N were
      sufficiently small to suggest that the system is in equilibrium with soils of the
      region.

PMID- 16594350
TI  - Estimation of particulate nutrient load using turbidity meter.
AB  - The "Nutrient Load Hysteresis Coefficient" was proposed to evaluate the
      hysteresis of the nutrient loads to flow rate quantitatively. This could classify
      the runoff patterns of nutrient load into 15 patterns. Linear relationships
      between the turbidity and the concentrations of particulate nutrients were
      observed. It was clarified that the linearity was caused by the influence of the
      particle size on turbidity output and accumulation of nutrients on smaller
      particles (diameter < 23 microm). The L-Q-Turb method, which is a new method for
      the estimation of runoff loads of nutrients using a regression curve between the
      turbidity and the concentrations of particulate nutrients, was developed. This
      method could raise the precision of the estimation of nutrient loads even if they
      had strong hysteresis to flow rate. For example, as for the runoff load of total
      phosphorus load on flood events in a total of eight cases, the averaged error of
      estimation of total phosphorus load by the L-Q-Turb method was 11%, whereas the
      averaged estimation error by the regression curve between flow rate and nutrient
      load was 28%.

PMID- 16594349
TI  - Indicator of risk of water contamination by phosphorus from Canadian agricultural
      land.
AB  - The indicator of risk of water contamination by phosphorus (IROWC_P) is designed
      to estimate where the risk of water P contamination by agriculture is high, and
      how this risk is changing over time based on the five-year period of data Census
      frequency. Firstly developed for the province of Quebec (2000), this paper
      presents an improved version of IROWC_P (intended to be released in 2008), which
      will be extended to all watersheds and Soil Landscape of Canada (SLC) polygons
      (scale 1:1, 000, 000) with more than 5% of agriculture. There are three
      objectives: (i) create a soil phosphorus saturation database for dominant and
      subdominant soil series of SLC polygons--the soil P saturation values are
      estimated by the ratio of soil test P to soil P sorption capacity; (ii) calculate
      an annual P balance considering crop residue P, manure P, and inorganic
      fertilizer P--agricultural and manure management practices will also be
      considered; and (iii) develop a transport-hydrology component including P
      transport estimation by runoff mechanisms (water balance factor, topographic
      index) and soil erosion, and the area connectivity to water (artificial drainage,
      soil macropores, and surface water bodies).

PMID- 16594351
TI  - Application of monitored natural attenuation to remediate a petroleum-hydrocarbon
      spill site.
AB  - Contamination of groundwater by petroleum-hydrocarbons is a serious environmental
      problem. The Monitored Natural Attenuation (MNA) approach is a passive
      remediation to degrade and dissipate groundwater contaminants in situ. In this
      study, a full-scale natural bioremediation investigation was conducted at a
      gasoline spill site. Results show that concentrations of major contaminants
      (benzene, toluene, ethylbenzene, and xylenes) dropped to below detection limit
      before they reached the downgradient monitor well located 280 m from the spill
      location. The results also reveal that natural biodegradation was the major cause
      of the observed contaminant reduction. The calculated natural first-order
      attenuation rates for BTEX and 1,2,4-trimethylbenzene (1,2,4-TMB) ranged from
      0.051 (benzene) to 0.189 1/day (1,2,4-TMB). Evidence for the occurrence of
      natural attenuation includes the following: (1) depletion of dissolved oxygen,
      nitrate, and sulfate; (2) production of dissolved ferrous iron, sulfide, and CO2;
      (3) decreased BTEX concentrations and BTEX as carbon to TOC ratio along the
      transport path; (4) increased alkalinity and microbial populations; (5) limited
      spreading of the BTEX plume; and (6) preferential removal of certain BTEX
      components along the transport path. Additionally, the biodegradation capacity
      (44.73 mg/L) for BTEX and 1,2,4-TMB was much higher than other detected
      contaminants within the plume. Hence, natural attenuation can effectively contain
      the plume, and biodegradation processes played an important role in contaminant
      removal.

PMID- 16594352
TI  - Comparison of several methods for BAP measurement.
AB  - It has been more important for management of water quality to estimate the amount
      of bioavailable phosphorus (BAP) in suspended solids (SS) entering lakes and
      estuaries. AGP test or extraction by 0.1 mol l(-1) NaOH (C-BOD) is widely used.
      Recently, highly bioavailable phosphorus (HBAP) was introduced to indicate a more
      easily soluble and bioavailable fraction using successive extraction by 0.1 mol
      l(-1) HCl and 0.1 mol l(-1) NaOH. New biologically measured BAP (B-BAP) using
      bacterial respiration activity was introduced in this paper. B-BAP was estimated
      from oxygen uptake rate (OUR), which was measured by a respiratory meter for BOD
      measurement using a pressure sensor. B-BAP is useful for a rapid and direct
      measurement of phosphorus bioavailability. B-BAP, HBAP and C-BAP in river SS were
      measured and compared with each other. The percentages of HBAP and B-BAP to PP
      were large in the urban river, while the percentage of NaOH-P or C-BAP was large
      in the rivers flowing in agricultural areas. By comparison with phosphorus
      fractions in paddy soil and activated sludge it was suggested that SS in the
      rivers flowing in agricultural areas mainly consisted of clay, silt or sand,
      while the SS in the urban river consisted of a large percentage of organic
      particles as well. Phosphorus in SS was suggested to be more easily bioavailable
      in the urban river than the rivers in agricultural areas. The ratio of C-BAP/B
      BAP was large in the rivers in agricultural areas and small in the urban river.
      As HBAP contents were almost similar to B-BAP contents in the river SS, HBAP can
      be a suitable index of phosphorus indicating easily and rapidly the bioavailable
      fraction in SS.

PMID- 16594353
TI  - Evaluation of atmospheric deposition of nitrogen to the Feitsui reservoir in
      Taipei.
AB  - This research studied how the air pollutants of urban areas affect a neighboring
      reservoir and its water quality. Through the atmospheric dispersion process, air
      pollutants move from the Taipei metropolitan to the Feitsui reservoir and enter
      the water body through dry and wet depositions. ISCST3 (Industrial Source Complex
      Short Term Model), an air quality model, was used to simulate dispersion, dry
      deposition and wet deposition of the air pollutants. Then the nitrogen loadings
      to the Feitsui Reservoir were evaluated. The results indicate that wet deposition
      places a greater burden than dry deposition does on the water body. Wet and dry
      deposition of NH4+ together make up a rather large proportion of the total
      pollution. The ranged from 21.9 to 25.2%. Those of nitrate make up a smaller
      proportion, ranged from 2.0 to 2.3%. If we take indirect deposition into account
      and calculate the NO3- and NH4+ together, the proportion is 15.9-17.6%.

PMID- 16594354
TI  - The unknown factors of treatment planning.

PMID- 16594355
TI  - The Dahl principle: creating space and improving the biomechanical prognosis of
      anterior crowns.
AB  - There is an increased demand for restoration of anterior teeth based on esthetic
      requirements. Oftentimes, the teeth restored are compromised and have minimal
      remaining dentin after undergoing root canal treatment. Reduction of nonaxial
      forces by controlling incisal guidance is essential in improving the long-term
      prognosis of such situations. Another common complication when crowning anterior
      teeth is the lack of palatal space for restorative material. This is often
      evident in patients with anterior tooth wear and deep overbite. This article
      describes the Dahl principle, a conservative method for controlling incisal
      guidance and gaining palatal space for restorative material. A case presentation
      is used to illustrate the concepts discussed.

PMID- 16594356
TI  - Survival rates of IPS empress 2 all-ceramic crowns and fixed partial dentures:
      results of a 5-year prospective clinical study.
AB  - OBJECTIVE: The aim of this prospective clinical study was to evaluate the
      survival rates of IPS Empress 2 (Ivoclar Vivadent) all-ceramic crowns and fixed
      partial dentures (FPDs) after an observation period of up to 5 years. METHOD AND
      MATERIALS: Forty-three patients (19 women and 24 men) were included in this
      study. The patients were treated with a total of 58 adhesive bonded IPS Empress 2
      restorations. A total of 27 single crowns were placed on molars and premolars,
      and 31 three-unit FPDs were placed in the anterior and premolar regions. Clinical
      follow-up examinations took place at 6, 12, 24, 36, 48, and 60 months after
      insertion. Statistical analysis of the data was calculated using the Kaplan-Meier
      method. RESULTS: Results of the 50-month analysis (interquartile range, 33 to 61
      months) showed that the survival rate was 100% for crowns and 70% for FPDs. Six
      failures that occurred exclusively in the three-unit FPDs were observed.
      Framework fractures were recorded in three FPD units where the connector
      dimensions did not meet the manufacturer specifications. Only one FPD exhibited
      an irreparable partial veneer fracture, and 2 FPDs showed evidence of biologic
      failures. The accuracy of fit and esthetic parameters were clinically
      satisfactory for crowns and FPDs. CONCLUSION: The results of this 5-year clinical
      evaluation suggest that IPS Empress 2 ceramic is an appropriate material for the
      fabrication of single crowns. Because of the reduced survival rates, strict
      conditions should be considered before the use of IPS Empress 2 material for the
      fabrication of three-unit FPDs.

PMID- 16594357
TI  - Oral lichen planus and malignant transformation: a retrospective follow-up study
      of clinical and histopathologic data.
AB  - OBJECTIVE: Patients in the stomatology service of the Department of Oral Surgery
      and Stomatology who were clinically and histopathologically diagnosed with oral
      lichen planus (OLP) in the years 1995 to 2001 were examined for a possible
      malignant transformation of a previously biopsied OLP site. METHOD AND MATERIALS:
      For the 145 patients included, the recordings were searched for initial
      localization and type of OLP lesion, potential noxious agents, distribution
      between symptomatic and asymptomatic OLP types, and for a malignant
      transformation of a known OLP site during the follow-up period up to December
      2003. RESULTS: The group comprised 47 men and 98 women with a mean age of 56.3
      years. Of the 497 lesions, almost half were classified as reticular or papular,
      predominantly located on the buccal mucosa, gingiva, and borders of the tongue.
      Four patients did not adhere to their scheduled control visits and were dropped
      from the study. During the follow-up period 4 patients developed malignant
      transformation of OLP. In 3 of these cases, dysplasia was present at the initial
      diagnosis of OLP. This results in a malignant transformation rate of 2.84% among
      the remaining 141 patients; if the 3 patients with initial dysplasia are
      excluded, the rate drops to 0.71%. CONCLUSIONS: Until further knowledge is
      derived from large prospective studies, the data supporting or negating a
      potential malignant character of OLP lesions remains inconclusive. Special
      emphasis has to be directed toward unified inclusion and exclusion criteria
      regarding clinical and histologic findings and identifiable risk factors to allow
      the comparison of different studies.

PMID- 16594358
TI  - Remineralized dentin lesions induced by glass ionomer demonstrate increased
      resistance to subsequent acid challenge.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that
      remineralized dentin lesions induced by glass ionomer are less vulnerable to
      subsequent acid challenge. METHOD AND MATERIALS: Baseline demineralized (BDe)
      lesions were created in 50 bovine dentin slices immersed for 3 weeks in acid
      solution. A resin-modified glass ionomer (RMGI) was applied to the specimens
      before immersion in salivalike solution to allow remineralization (Re) for 2
      weeks (V2W) or 6 weeks (V6W). Resin-modifed glass ionomer was coated to block
      further ion release before a 3-week immersion in acid solution as a second
      demineralization (SDe). Control groups (C2W and C6W) were done simultaneously
      without RMGI. In another group, RMGI was left undisturbed (V2W+) to allow
      continuous ion release during SDe. Mineral content was converted from
      microradiographs, after BDe, Re, and SDe steps. Changes in mineral content were
      calculated and compared between groups. RESULTS: The remineralized surface zone
      was maintained after SDe, but the lesion body became deeper. Percentage of
      mineral loss from SDe was not significantly different between V2W and C2W (t
      test, P > .05). When remineralization was extended to 6 weeks, V6W showed
      significantly less mineral loss than C6W. Mineral loss was lowest when RMGI was
      not blocked (V2W+). CONCLUSION: Dentin lesions remineralized in the presence of
      RMGI maintained the highly mineralized surface zone when subjected to second
      demineralization. However, the remineralized surface zone could not prevent
      advance of the lesion body. The subsequent demineralization was markedly reduced
      by extending the remineralization period or by leaving the RMGI undisturbed to
      resume ion release.

PMID- 16594359
TI  - Removable partial denture abutments restored with all-ceramic surveyed crowns.
AB  - All-ceramic crowns are used as alternatives to conventional metal-ceramic crowns
      for the restoration of single teeth. Traditionally all-ceramic restorations
      possessed physical properties that contraindicated their use in many treatment
      situations. The strength that zirconia ceramics exhibit seems to support the
      hypothesis that, in specific situations, an all-ceramic crown may be used to
      restore removable partial denture (RPD) abutments in areas previously reserved
      for metal or metal-ceramic restorations. Abutments for RPDs may now be fabricated
      with Procera AllZirkon with the classically prepared guide planes and rest seats.
      This article provides an overview of a technique for the fabrication of a
      zirconia-based crown to be used in conjunction with removable partial dentures
      using the Procera CAD/CAM technology.

PMID- 16594360
TI  - Fracture strength of teeth restored with all-ceramic posts and cores.
AB  - OBJECTIVE: The purpose of this in vitro investigation was to evaluate the
      fracture strength of endodontically treated teeth restored with different all
      ceramic posts and cores. METHOD AND MATERIALS: Seventy-two endodontically treated
      human maxillary central incisors were divided into 3 groups with 24 teeth each
      and restored with 1 of the following methods: prefabricated zirconia ceramic
      posts and resin composite buildups; zirconia ceramic posts and copy-milled
      alumina ceramic cores (2-piece technique), or copy-milled all-ceramic posts and
      cores made from a zirconia-reinforced glass-infiltrated alumina ceramic (1-piece
      technique). Each group was divided into 3 subgroups of 8 samples each, consisting
      of teeth that did not receive crown restorations and were stored for 60 days,
      teeth restored with all-ceramic crowns and stored for 60 days, and teeth restored
      with all-ceramic crowns and subjected to 1.2 million loading cycles with 30 N in
      a chewing simulator. RESULTS: The mean fracture strengths ranged from 205 to 522
      N. Prefabricated zirconia posts and resin composite buildups showed a
      statistically significantly lower fracture strength after chewing simulation than
      teeth restored with prefabricated zirconia posts and alumina ceramic cores.
      CONCLUSION: All-ceramic posts and cores made with the 2-piece technique showed
      promising fracture strengths under the tested conditions.

PMID- 16594362
TI  - Dental fear and anxiety levels of patients attending a dental clinic.
AB  - OBJECTIVE: The aim of this study was to evaluate the anxiety levels of patients
      attending a university oral diagnosis clinic. Avoidance, felt physiologic
      responses, and the most fear-producing stimuli of dental treatment were also
      evaluated. METHOD AND MATERIALS: A total of 1,437 patients were asked to complete
      a questionnaire consisting of the Dental Anxiety Scale (DAS), Dental Fear Scale
      (DFS), and questions about age, gender, education level, and frequency of dental
      visits. The patients were grouped according to gender and divided into 5 age
      categories. Statistical analysis was made by descriptive statistics, two
      proportion z test, analysis of variance, Tukey's Honestly Significant Difference
      test, and Scheffe test. RESULTS: The mean DAS score was 9.52 (SD 4.08) for
      females, 7.96 (SD 3.30) for males, and 8.76 (SD 3.80) for the total sample. There
      was no statistically significant difference between the mean DAS scores of age
      groups. Patients with a primary school education and those who had never visited
      the dentist had the highest anxiety scores. According to the DFS, the most felt
      autonomic response was increased heart rate, and the most fear-producing stimuli
      were the sight of the needle (25.1%) and sensation of the injection (24.1%). Of
      the patients 10.5% avoided calling for an appointment, and 4.9% canceled or did
      not appear for appointment. CONCLUSION: Some patients are afraid of some of the
      stimuli involved with dental treatment. This could affect the patient-dentist
      relationship and the dental treatment plan; therefore, before dental treatment,
      patients' anxiety and fear levels should be assessed.

PMID- 16594361
TI  - Effect of fluoride-releasing liner on demineralized dentin.
AB  - OBJECTIVE: The aim of this study was to evaluate the remineralization of residual
      demineralized dentin underneath restorations by fluoride-releasing liners in
      vitro. METHOD AND MATERIALS: Two glass-ionomer cement liners, Lining Cement (GC)
      and RK-141A (GC), and two light-cured resin liners with and without 5 wt% NaF
      were used in this study. The resin liners were made by mixing TEGDMA and bis-GMA.
      Class 5 cavities were prepared on extracted human premolars. Demineralized dentin
      was promoted by using a bacterial caries induction system at the cavity floor.
      Cavities were restored with a resin composite following application of each
      liner. Specimens were then stored for 4 weeks at 37 degrees C and 100% humidity.
      After storage, the specimens were cut through the restorations, and axial
      sections of about 80-microm thickness were prepared. Contact microradiographs
      were taken, and the radiopacity of the demineralized dentin layer underneath the
      liner was analyzed. RESULTS: The ratios of radiopacity of demineralized dentin
      under the fluoride-releasing liners were significantly higher than those under
      the resin liner without fluoride release. Although the amounts of fluoride
      release from the glass-ionomer cement liners were lower than that from the resin
      liner with fluoride release, there were no significant differences in the ratios
      of radiopacity in demineralized dentin layers among the 3 liners with fluoride
      release. CONCLUSION: Although the fluoride released from liners can enhance
      remineralization of demineralized dentin, the amount of fluoride release does not
      affect the ratio of radiopacity in the remineralized dentin.

PMID- 16594363
TI  - An in vitro investigation into the surface roughness of 2 glazed, unglazed, and
      refinished ceramic materials.
AB  - OBJECTIVE: It is common practice for clinicians to adjust the porcelain surfaces
      of dental prostheses. The change in surface roughness after different surface
      finishing techniques has attracted the attention of prosthodontists. The present
      study was undertaken to investigate the average surface roughness of 2 dental
      ceramics: IPS Empress 2 (layering glass-ceramic, Ivoclar Vivadent) and In
      Ceram/Vitadur Alpha (Vita), either glazed, unglazed, or refinished using
      different techniques. METHOD AND MATERIALS: Disks of 6-mm diameter and 2-mm
      thickness were prepared from IPS Empress 2 and In-Ceram Alumina/Vitadur Alpha
      ceramics. Specimens were finished for 1 minute to the various stages provided in
      the sequence of instruments in the Shofu porcelain veneer kit. The average
      roughness measurements were taken from each specimen with a surface roughness
      tester. RESULTS: Significant differences in surface roughness were observed
      between the ceramics and among the finishing techniques used for both IPS Empress
      2 and In-Ceram/Vitadur Alpha. It was found that unglazed IPS Empress 2 is rougher
      than unglazed In-Ceram/Vitadur Alpha. CONCLUSION: Regardless of the type of
      ceramic or pretreatment, any adjusted ceramic restoration should be reglazed or
      subjected to a finishing sequence that is followed through to a final stage of
      polishing with diamond paste.

PMID- 16594364
TI  - Retrieval of amalgam from the root canal space.
AB  - Removal of foreign objects from the root canal can be very frustrating. The use
      of a variety of instruments and techniques has been suggested for the retrieval
      of obstacles from root canals during endodontic treatment. This article describes
      a method for retrieving a large mass of amalgam restoration that was wedged into
      the root canal. The amalgam, which had served as the provisional restorative
      material during apexification of an immature ante rior tooth, was inadvertently
      pushed into the root canal. After the mass was bypassed, the amalgam was loosened
      with the aid of copious irrigation, chelation, and flotation. Hedstrom files
      twisted around the object allowed sufficient grip for its retrieval, enabling
      completion of the root canal treatment.

PMID- 16594365
TI  - Narrative research.

PMID- 16594366
TI  - Approaches to reflexivity in qualitative research.

PMID- 16594367
TI  - Health of immigrant Hispanic families: narrative and phenomenological
      hermeneutics.

PMID- 16594368
TI  - Fears, worries and experiences of first-year pre-registration nursing students: a
      qualitative study.

PMID- 16594369
TI  - Building trust between the older adults and researchers in qualitative inquiry.

PMID- 16594370
TI  - Issues in phenomenological nursing research: the combined use of pain diaries and
      interviewing.

PMID- 16594371
TI  - Choosing an appropriate method of data collection.

PMID- 16594372
TI  - A commitment to peace: a doctor's tale. A short, selected history of the Medical
      Association for Prevention of War.

PMID- 16594373
TI  - The global war on terror: four years on.
AB  - The progress of the global war on terror in the four years since the 9 September
      2001 attack on New York and Washington is surveyed, with particular reference to
      its objective of curtailing the activities of al-Qaida, the situation in
      Afghanistan and Iraq, and the threat to the United States from the 'axis of
      evil'. It is suggested that the US is unlikely to withdraw from Iraq in
      particular because of its dependency upon access to Middle East oil in the
      foreseeable future, and accordingly that the global war on terror is likely to
      continue for several years at least.

PMID- 16594374
TI  - Terror breeds terrorists.
AB  - Terrorism can be carried out by the state or by its citizens. The latter may be
      labelled 'freedom fighters' or 'terrorists' depending on the political context.
      One of the most important aetiological factors driving Islamic terrorists is the
      experience of alienation and shame. This sense of being made to feel totally
      invalidated, of feeling worthless in the eyes of the other, is at the root of
      rage and violent revenge, implying that the way the current 'War on Terror' is
      being fought by the United States and the United Kingdom can only lead to more
      terrorism and danger for our society.

PMID- 16594375
TI  - The failure of international action against terrorism.
AB  - Progress on the so-called 'War on Terrorism' is slow. There is no agreed
      definition of terrorism and no consistent government policy in respect of it.
      Consideration of terrorism ignores the role of some governments in what could be
      regarded as terrorist activity, often with the connivance of others for reasons
      of political expediency. The special case of suicide terrorism is discussed in
      detail. It is concluded that the world is now exposed to a new form of warfare,
      and that even with new military thinking this could continue for perhaps decades
      to come.

PMID- 16594376
TI  - Winning the war on terror: psychology as a strategic framework.
AB  - International relations is fundamentally about people. Psychology provides a wide
      range of tools to understand the rise of Islamic fundamentalist terrorism and
      offers part of the framework for its resolution. Western societies need to avoid
      being consumed with fear, revenge or anger which might lead to polarisation and
      perpetuate the cycle of violence. Understanding the enemy and the virulence of
      their ideas is essential to winning the hearts and minds of their potential
      supporters through dialogue, public diplomacy and foreign policy. The West needs
      to build trust, relationships, reputation and address double standards in its
      behaviour in order to build a global coalition of people with shared values. The
      concept of 'war on terror' has been damaging, not least by inhibiting western
      societies from the self-reflection required to overcome the challenge of
      terrorism.

PMID- 16594378
TI  - After The Wall: a visit to Palestine.

PMID- 16594377
TI  - Towards a common global ethic: a rational approach to terrorism.

PMID- 16594379
TI  - A view from Pyongyang; a year of anniversaries; one bullet stories at the United
      Nations.

PMID- 16594380
TI  - Lange's legacy: a strong nuclear-free law in New Zealand.

PMID- 16594381
TI  - War as a fashion.

PMID- 16594382
TI  - CA mega-mergers may reshape capitation landscape.

PMID- 16594383
TI  - California IPA reaps profits in rebounding market.

PMID- 16594385
TI  - Contrary to media reports, HMO enrollments stable in recent years, study finds.

PMID- 16594386
TI  - Capitation common in multispecialty groups, but few specialties take risk.

PMID- 16594384
TI  - Gatekeepers provide positive influence on mammography, Pap screening rates.

PMID- 16594387
TI  - In vivo axial dynamization of canine tibial fractures using the Securos external
      skeletal fixation system.
AB  - Bilateral transverse mid-shaft tibial osteotomies, with a 4-mm gap, were
      performed in purpose-bred research dogs and stabilized using a Securos Type 2
      external skeletal fixotor (ESF). Full (100%) axial dynamization of one randomly
      selected ESF in each dog was performed at 31 days postoperatively. Caudo-cranial
      radiographs were obtained at weekly intervals, which were qualitatively and
      quantitatively evaluated (densitometry and ImageJ analysis). The dogs were
      euthanatized 13 weeks postoperatively, at which time dual energy x-ray
      absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT),
      mechanical testing in torsion, and qualitative histological analysis were
      performed. A two-tailed paired Student's t-test was performed for statistical
      analysis of all parameters of interest, with significance set at p < 0.05. Three
      of five dynamized bones bridged quicker, and four of five dynamized bones
      appeared to have greater callus formation, however, statistically significant
      differences could not be definitively determined. Statistically significant
      differences were not found with densitometry (any time frame), DEXA, pQCT,
      torsional stiffness or maximum torque. Despite the lack of statistically relevant
      data, trends were observed with larger callus size and density in the dynamized
      tibiae. The dynamized tibiae appeared to fracture more consistently outside of
      the area of the healing callus as compared to the control tibiae. Histological
      evaluation showed greater remodelling in four of five control limbs when compared
      to the dynamized limb. Dynamization at 31 days post-operatively may delay bone
      remodelling, despite a trend towards a larger callus size. The results of this
      study failed to show a definitive role for early full axial dynamization.

PMID- 16594388
TI  - Comparison of tenoscopic and ultrasonographic methods of examination of the
      digital flexor tendon sheath in horses.
AB  - The purpose of this study was to compare sonographic and tenoscopic findings with
      the purpose of establishing the accuracy and limitations of ultrasonograophy as a
      non-invasive diagnostic modality in evaluating the DFTS and its enclosed tendons.
      The medical records from 22 horses which underwent tenoscopic desmotomy of the
      palmar/plantar annular ligament were evaluated in a retrospective study. The
      qualitative assessment of sonogrophic and tenoscopic findings were documented for
      the digital flexor tendon sheath (DFTS), the palmar/plantar annular ligament
      (PAL), the superficial digital flexor tendon (SDFT) and the deep digital flexor
      tendon (DDFT). The abnormalities diagnosed sonographically within the DFTS were
      verifiable tenoscopically with a sensitivity of 90.9% and a specificity of 53.8%.
      The positive predictive value of sonographic examination at the DFTS was 62.5%.
      The sensitivity of the sonographic examination at the PAL was 68.8%, the
      specificity was 50% and the positive predictive value 73.3%. Sonographic
      examination of the SDF tendons revealed abnormal findings in 12 tendons. The
      tenoscopic examination confirmed these findings on six tendons when they had a
      pronounced fibrillated or rough tendon surface or tear on the border. Six
      superficial flexor tendons and seven deep digital flexor tendons had
      abnormalities seen tenoscopically which were not visible on sonographic
      examination. Sonographic examination located lesions of the DDFT in four limbs.
      On tenoscopic examination the lesions could be detected in seven other DDF
      tendons, including signs of inflammation at the tendon surface that were not seen
      ultrasonographically (sensitivity 36.4%). Recognition of the limitations of
      sonographic results should be kept in mind so as not to misinterpret findings,
      especially if echogenic materials are observed.

PMID- 16594389
TI  - Comparison of anatomical tibial plateau angle versus observer measurement from
      lateral radiographs in dogs.
AB  - This study was conducted to compare the anatomical tibial plateau angle (TPA)
      with that measured by observers from a lateral radiograph of the limb, the
      hypothesis being that there would not be any statistically significant
      differences between the observer measured TPA and the true anatomical TPA. Twelve
      pelvic limbs from skeletally mature greyhound cadavers, without any clinical or
      radiographic evidence of stifle pathology, were used in this study. The
      radiographs were taken of each limb in a lateral position with the primary beam
      centered over the tibial eminences and collimated to include the stifle and tarso
      crural joints. For subsequent radiographs, Kirschner wires were inserted to
      enable identification of the tibial plateau. The TPA was then measured, by three
      observers, from the plain radiographs and by one observer from the marked
      radiographs. The mean observer TPA was 24.4 degrees (range 17-30 degrees) and the
      mean anatomical TPA was 23.8 degrees (range 15-31 degrees). The mean and median
      discrepancy between the anatomical TPA and the observer TPA was negative and very
      small (- 0.64 degrees and 0 degrees). The magnitude of the discrepancy between
      individual measurements made by the observers tended to overestimate small angles
      and underestimate the large ones, and this trend is statistically significant.
      These results suggest that the measurements made by observers accurately
      represent the anatomical slope of the tibial plateau. Therefore, observer TPA is
      suitable for the planning and assessment of TPLO procedures. However, as the
      anatomical TPA moves away from a median angle (23.25 degrees) the magnitude of
      error in the measurement increases.

PMID- 16594390
TI  - In vitro biomechanical comparison of limited contat dynamic compression plate and
      locking compression plate.
AB  - The locking compression plate (LCP) supports biological osteosynthesis by
      functioning as an internal fixator, rather than as a full or limited contact bone
      plate which must be adequately contoured and affixed directly to the bone for
      stable internal fixation of the fracture. In order to help justify the use of the
      LCP in our veterinary patients, in vitro biomechanical testing was performed
      comparing the LCP to the conventional limited contact dynamic compression plate
      (LC-DCP) in canine femurs. We hypothesized that the LCP construct would be at
      least as stiff under bending and torsional loads as the LC-DCP. The LCP and LC
      DCP were applied over a 20-mm osteotomy gap to contralateroal bones within each
      pair of 14 femora. Non-destructive four-point bending and torsion, and cyclical
      testing in torsion were performed. The constructs were then loaded to failure in
      torsion. In medial-lateral and lateral-medial structural bending, significant
      differences were not found between the LCP and LC-DCP, however, at the gap, the
      LCP construct was stiffer than the LC-DCP in lateral-medial bending. Significant
      differences in behaviour over time were not noted between the plate designs
      during cyclical testing. When loading the constructs to failure in internal
      rotation, the LC-DCP failed at a significantly lower twist angle (P = .0024) than
      the LCP. Based on the similar performance with loading, the locking compression
      plate is a good alternative implant for unstable diaphyseal femoral fracture
      repair in dogs.

PMID- 16594391
TI  - The effect of axial and abaxial release on meniscal displacement in the dog.
AB  - The meniscal release (MR) is used to minimize meniscal pathology after Tibial
      Plateau Leveling Osteotomy (TPLO) surgery. The purposes of this study were: (i)
      to describe meniscal orientation in a unaltered cadaveric canine stifle, a
      cruciate deficient stifle, TPLO repaired stifle with and without the MR using
      magnetic resonance imaging; (ii) to determine if the abaxial release is
      equivalent to the axial release in its ability to affect caudal pole displacement
      in a TPLO repaired stifle and (iii) to evaluate with MRI the effect of MR on the
      femorotibiol articular cartilage contact area in a TPLO repaired stifle. Briefly,
      cadaver limbs were placed into a jig designed to mimic a weight-bearing stance at
      140 degrees and 90 degrees at the stifle. The limbs were sequentially evaluated
      from the unaltered state; after cranial cruciate ligament transection; after TPLO
      stabilization; and finally after a meniscal release. No significant difference
      was found between the intrameniscal area (IMA) of the abaxial and axial meniscal
      releases although there was an increase in the IMA after the meniscal release
      compared to the IMA in the normal, cranial cruciate ligament deficient stifle,
      and TPLO stabilized stifle. In the abaxial release, a meniscal remnant remained
      in situ and provided a space effect between the femur and the tibial plateau.
      This is in contrast to the axial meniscal release, where the entire caudal pole
      of the medial meniscus relocated caudolaterally and consequently permitted more
      direct femorotibial contact. Overall, however, there was evidence of caudal pole
      compression of the medial meniscus throughout the MRI series which was
      ameliorated by either of the MR procedures.

PMID- 16594392
TI  - Radiographic and clinical changes of the patellar tendon after tibial plateau
      leveling osteotomy 94 cases (2000-2003).
AB  - Patellar tendon thickening (PTT) and patellar tendinosis (PTS) have been
      discussed in the veterinary literature as a post-operative complication of tibial
      plateau leveling osteotomy (TPLO). The purpose of this study was to define
      radiographic PTT, determine the frequency of and risk factors for PTT and PTS,
      and describe the clinical and histopathological findings of PTS after TPLO. We
      hypothesized that the location of the osteotomy alters forces placed on the
      patelloar tendon resulting in PTT or PTS. Radiographs and medical records from 83
      dogs undergoing 94 TPLO procedures were retrospectively evaluated. Two months
      post-operatively, 19 dogs (20.2%) had a normal patellar tendon or mild PTT, 51
      (54.3%) had moderate PTT, and 24 (25.5%) had severe PTT. Seven of the 24 dogs
      (7.4%) with severe PTT had clinical signs consistent with PTS. Only dogs with
      severe PTT developed PTS (p < 0.0001). The risk factors for the development of
      PTT include: a cranial osteotomy, a partially intact cranial cruciate ligament
      (CCL) in conjunction with a cranial osteotomy, and post-operative tibial
      tuberosity fracture. The only risk factor identified for the development of PTS
      was a partially intact CCL. Four dogs with PTS improved with conservative therapy
      and one improved with surgical treatment. Two dogs had tendon biopsies with
      histopothological review that showed tendon degeneration with lack of
      inflammation. As only the dogs with severe PTT develop PTS, a caudal osteotomy
      for the prevention of PTT and subsequent PTS is recommended.

PMID- 16594393
TI  - Incomplete humeral condylar fracture in two English Pointer dogs.
AB  - Incomplete humeral condylar fracture was diagnosed by means of radiology, CT,
      scintigraphy, arthroscopy and bone biopsy in two English Pointer dogs. In both
      cases an acute thoracic limb lameness, unrelated to a known episode of major
      trauma, was observed. Incomplete humeral condylar fracture, mainly described in
      the Spaniel breeds, has been recently diagnosed in Labrador retrievers,
      Rottweiler, German Wachtel and other breeds. The pathogenesis of the condition is
      still unknown, but incomplete ossification of the humeral condyle and mechanical
      stress, alone or associated, have to be considered. However, our clinical and
      histopathological data lead us to believe that in Pointers, high performance
      dogs, the mechanical stress can assume a critical ethiopathogenetic role.

PMID- 16594394
TI  - Diagnosis and treatment of hind limb muscle strain injuries in 22 dogs.
AB  - The anamnesis was obtained from the medical records of 22 dogs diagnosed with
      hind limb muscle strain injury over a four-year period. The signalment, history,
      diagnostic imaging and clinical findings, treatment and outcome are described.
      The affected dogs were primarily from large breeds. Although only a few clients
      reported a specific injury, 11 dogs were admitted for an acute onset of lameness
      of unknown origin. The hip adductor muscles were affected in 21 dogs, and 11 dogs
      had previously undergone orthopaedic surgery of the affected limb. The dogs were
      primarily diagnosed by physical examination, although the diagnosis was confirmed
      with ultrasound imaging in the two most recent cases. Neither concurrent
      orthopoedic nor neurological disease was found during the study period in four of
      22 dogs, and another three dogs had only mild radiographic coxofemoral
      osteoarthritis that did not cause any clinical signs during the study period. All
      of the dogs were treated medically with some combination of rest, physical
      therapy, methocarbamol, and a non-steroidol anti-inflammatory drug (NSAID). The
      injury-associated lameness improved, or completely resolved, with conservative,
      non-surgical therapy in most dogs. Of the 15 dogs available for follow-up (mean
      577 days), eight had complete resolution of their clinical signs, two showed
      significant improvement, and one showed some improvement. Muscle strain injury
      may be an under-diagnosed cause or contributor to acute hind limb lameness in
      large breed dogs, either alone or following orthopoedic surgery.

PMID- 16594396
TI  - Sonographic assisted diagnosis and treatment of bilateral gastrocnemius tendon
      rupture in a Labrador retriever repaired with fascia lata and polypropylene mesh.
AB  - This case report describes a four-year-old, eighty-five pound, male neutered
      Labrador retriever that was admitted with unilateral lameness and clinical
      findings consistent with a unilateral gostrocnemius tendon rupture. A prior
      history of trauma was not identified. Ultrasonagraphic evaluation revealed
      bilateral gastrocnemius tendon defects in which approximately 80% of the tendon
      was ruptured on the clinically normal side, yet mechanical function and
      anatomical length were not apparently altered. Bilateral surgical repair was
      performed utilizing primary tendon reconstruction, supported by fascia lata,
      autograft and polypropylene mesh. The repairs were protected with rigid costs for
      two weeks following surgery, and replaced with orthotics through the complete
      recovery period. Orthotics provided semi-rigid support and allowed removal for
      controlled intermittent physical therapy. This surgical repair technique,
      combined with orthotic support, allowed for early mobilization and good ultimate
      outcome for a complicated bilateral condition.

PMID- 16594395
TI  - Feline cranial cruciate rupture: 17 cases and a review of the literature.
AB  - Seventeen cases of feline cranial cruciate ligament rupture are presented. The
      cases are divided into two groups: those with traumatic multiligamentous damage,
      and those with isolated cranial cruciate ligament rupture without a history of
      trauma. The cats that had suffered cruciate ligament rupture were heavier than
      the general population of cats and there is evidence reported that this injury
      parallels the degenerative cranial cruciate ruptures seen in overweight small
      breed dogs. The limited literature on this subject is reviewed including
      approaches to treatment.

PMID- 16594397
TI  - At the crossroads: making the transition to hospice.
AB  - OBJECTIVE: Previous studies reveal that many terminally ill patients never
      receive hospice care. Among those who do receive hospice, many enroll very close
      to the time of death. Nationally, between 1992 and 1998, the median length of
      stay at hospice declined 27%, from 26 to 19 days. In our prior study of 206
      patients diagnosed with terminal cancer and using hospice, we found that one
      third enrolled with hospice within 1 week prior to death. Late hospice enrollment
      can have deleterious effects on patients and their family members. The aim of the
      present study was to characterize common experiences of patients and primary
      family caregivers as they transition to hospice, focusing on caregiver
      perceptions of factors that might contribute to delays in hospice enrollment.
      METHODS: We conducted in-depth interviews with a purposive sample of 12
      caregivers selected from a population of primary family caregivers of patients
      with terminal cancer who enrolled with hospice in Connecticut between September
      2000 and September 2001. Respondents represented different ages, genders, and
      kinship relationships with patients. Respondents were asked about the patient's
      care trajectory, how they first learned about hospice, and their experiences as
      they transitioned to hospice. NUD*IST software was used for qualitative data
      coding and analysis. RESULTS: Constant comparative analysis identified three
      themes common to the experience of transitioning to hospice: (1) caregivers'
      acceptance of the impending death, (2) challenges in negotiating the health care
      system across the continuum of care, and (3) changing patient-family dynamics.
      SIGNIFICANCE OF RESULTS: Identification of these themes from the caregivers'
      perspective generates hypotheses about potential delays in hospice and may
      ultimately be useful in the design of interventions that are consistent with
      caregivers' needs.

PMID- 16594398
TI  - Determinants of death in an inpatient hospice for terminally ill cancer patients.
AB  - OBJECTIVE: Despite the strong emphasis on home-based end-of-life care in the
      United States and the recognition of dying at home as a gold standard of quality
      of care, hospice home care is not a panacea and death at home may not be feasible
      for every terminally ill cancer patient. Admission to an inpatient hospice and
      dying there may become a necessary and appropriate solution to distressing
      patients or exhausted families. However, the factors associated with death in an
      inpatient hospice have not been examined in previous studies. METHODS: A
      prospective cohort study was conducted to investigate the determinants of death
      in an inpatient hospice for terminally ill cancer patients. Approximately two
      fifths (40.8%) of the 180 terminally ill cancer patients in this study died in
      inpatient hospices over the 3-year study period. RESULTS: Results from Cox
      proportional hazards model with adjustment for covariates revealed several
      factors that were significantly associated with dying in inpatient hospice, as
      opposed to home, in a nursing home, or in the hospital. Patients were more likely
      to die in an inpatient hospice if they received hospice care before death (hazard
      ratio [HR] = 7.32, 95% confidence interval [CI]: 3.21-16.67), if they had a
      prestated preference to die in an inpatient hospice (HR = 4.86, 95% CI: 2.24
      10.51), if they resided in New Haven County (HR = 1.70, 95% CI: 1.00-2.93), or if
      they experienced higher levels of functional dependency (HR = 1.05, 95% CI: 1.02
      1.08). SIGNIFICANCE OF RESULTS: The high prevalence of inpatient hospice deaths
      for terminally ill cancer patients in this study was related to the local health
      care system characteristics, health care needs at the end of life, and personal
      preference of place of death. Findings from this study may shed light on future
      directions for developing end-of-life care tailored to the needs of cancer
      patients who are admitted to hospices and eventually die there.

PMID- 16594399
TI  - Spiritual issues and needs: perspectives from patients with advanced cancer and
      nonmalignant disease. A qualitative study.
AB  - OBJECTIVE: Health care professionals and policy makers acknowledge that spiritual
      needs are important for many patients with life-limiting illnesses. We asked such
      patients to describe their spiritual needs and how these needs may impinge on
      their physical, psychological, and social well-being. Patients were also
      encouraged to explain in what ways their spiritual needs, if they had any, could
      be addressed. METHODS: We conducted two qualitative interviews, 3 months apart,
      with 20 patients in their last year of life: 13 patients with advanced cancer and
      7 with advanced nonmalignant illness. We also interviewed each patient's general
      practitioner. Sixty-six interviews were tape-recorded, transcribed, and analyzed.
      RESULTS: Patients' spiritual needs centered around their loss of roles and self
      identity and their fear of dying. Many sought to make sense of life in relation
      to a nonvisible or sacred world. They associated anxiety, sleeplessness, and
      despair with such issues, which at times resulted in them seeking support from
      health professionals. Patients were best able to engage their personal resources
      to meet these needs when affirmed and valued by health professionals.
      SIGNIFICANCE OF RESULTS: Enabling patients to deal with their spiritual needs
      through affirmative relationships with health professionals may improve quality
      of life and reduce use of health resources. Further research to explore the
      relationship between spiritual distress and health service utilization is
      indicated.

PMID- 16594400
TI  - Reliability and validity of the Japanese version of the Support Team Assessment
      Schedule (STAS-J).
AB  - OBJECTIVE: The aim of this project was to develop an appropriate and valid
      instrument for assessment by medical professionals in Japanese palliative care
      settings. METHODS: We developed a Japanese version of the Support Team Assessment
      Schedule (STAS-J), using a back translation method, and tested its reliability
      and validity. In the reliability study, 16 nurses and a physician who work in a
      palliative care unit evaluated 10 hypothetical cases twice at 3-month intervals.
      For the validity study, external researchers interviewed 50 patients with
      matignancy and their families and compared the results with ratings by the nurses
      in the palliative care unit. RESULTS: Our results with hypothetical cases were:
      interrater reliability weighted kappa = 0.53-0.77 and intrarater reliability
      weighted kappa = 0.64-0.85. In the validity study comparing nurse evaluations and
      the results of interviews with patients and families, complete agreement was 36
      70%, and close agreement (+/-1) was 74-100%. As a whole, weighted kappa were low:
      between -0.07 and 0.51. Our results were similar to those in the United Kingdom
      and Canada. SIGNIFICANCE OF RESULTS: Although this research was conducted under
      methodologically limited conditions, we concluded that the STAS-J is a reliable
      tool and its validity is acceptable. The STAS-J should become a valuable tool,
      not only for daily clinical use, but also for research.

PMID- 16594401
TI  - Parents dying of cancer and their children.
AB  - OBJECTIVE: We reviewed our experience with 28 consecutive children referred for
      assessment and intervention. These were the children of patients with terminal
      cancer referred to the Palliative Care and Symptom Control Service. In all cases
      the dying parent was a biological parent. METHODS: Eleven parameters were
      assessed in each of 29 children and their incidence was calculated. The children
      and their parents were seen in a semistructured interview, together as well as
      separately. The parameters were: seeking reassurance (82), becoming a caretaker
      (79), inability to separate from parent (79), anger about feeling abandoned (68),
      despair (57), guilt (54), discipline problems, aggressive behavior (46), denial
      (39), blame of others (21), and fear for the child's own health (18). RESULTS:
      Our results suggest that children with dying parents manifest significant
      distress as well as a greater understanding of their parent's illness than is
      usually suspected. SIGNIFICANCE OF RESULTS: Timely intervention by a child
      psychiatrist or other mental health professional with proven competence in
      working with children can help children to better cope with the death and dying
      of their parent and ameliorate the process of bereavement following the parent's
      death. Because of our small sample, we cannot generalize about all of the
      findings. Further research is required to characterize the level of distress in
      the children and the long-term impact in their overall adjustment to life.

PMID- 16594402
TI  - The schedule of attitudes toward hastened death: validation analysis in
      terminally ill cancer patients.
AB  - OBJECTIVE: The faithful translation of the English version of the Schedule of
      Attitudes toward Hastened Death (SAHD) into Greek and its validation as an
      assessment tool in terminally ill cancer patients receiving palliative treatment.
      METHODS: 120 terminally ill cancer patients attending a Palliative Care Unit, at
      the University of Athens, Greece, between June 2003 and November 2003 for
      palliative treatment. RESULTS: SAHD would be a useful instrument for measuring
      desire for hastened death with valid psychometric properties in a Greek cancer
      population. The SAHD demonstrated high reliability. Desire for hastened death was
      significantly associated with Hospital Anxiety and Depression Scale (HAD)
      depression (r = 0.607, p < 0.0005) and substantially correlated with HAD anxiety
      (r = 0.502, p < 0.0005). "Pain intensity" had a moderate correlation with SAHD
      scores (r = 0.28, p = 0.01) and SAHD scores correlated significantly with "pain
      interference in mood" (r = 0.38, p = 0.01) and in "enjoyment of life" (r = 0.34,
      p = 0.03). SAHD correlation with quality of life was statistically significant (r
      = -0.38, p < 0.01) as was health status (r = -0.36, p < 0.01). Patients with a
      Poor Performance Status (from Eastern Cooperative Oncology Group scale)
      correlated significantly with high scores in SAHD (p = 0.038). Factor analysis
      supported the unidimentionality of the measurement. SIGNIFICANCE OF RESULTS: SAHD
      could be a useful and valid instrument for measuring desire for hastened death in
      Greek terminally ill cancer patients.

PMID- 16594403
TI  - A pilot study of the impact of a grief camp for children.
AB  - OBJECTIVE: Research indicates that children benefit from supportive interventions
      to help them cope with the loss of a loved one. The aim of this pilot study was
      to evaluate children's perceptions of the effectiveness of a grief camp. METHODS:
      Semistructured interviews were performed with 18 children who attended a weekend
      long grief camp. Children also responded to follow-up interviews via telephone.
      Their parents also completed surveys before camp began and either after camp
      ended or at a follow-up evaluation. Data were analyzed using descriptive
      statistics and content coding to uncover key themes in the interviews. RESULTS:
      Children reported that art activities helped them to express feelings about their
      grief and release feelings of sadness and worry related to the death. Parents and
      children felt that the camp was a positive experience and that the children
      benefited from being in groups with peers who had also lost family members.
      SIGNIFICANCE OF RESULTS: Evaluating the impact of grief camps, using practical
      methods such as the ones for this study, is important, as these camps are
      becoming more popular interventions. Children and parents may benefit from
      contact at specified follow-up periods after camp to determine if they would
      benefit from further therapy. Results also provide evidence of the success of
      this program, which supports the need for funding these types of interventions.

PMID- 16594405
TI  - Hope at the end of life: making a case for hospice.

PMID- 16594404
TI  - Somatization disorder and cancer: a case history and review.
AB  - Cancer pain generally has a physical cause exacerbated to varying degrees by
      psychological, social, and spiritual factors. This article describes the case
      history of a cancer patient with severe pain for which no physical cause could be
      found, who was subsequently found to have a history of somatization disorder.
      There follows a review of the literature, with specific reference to the
      difficulties of managing somatization in the context of cancer.

PMID- 16594406
TI  - Is there a model for demonstrating a beneficial financial impact of initiating a
      palliative care program by an existing hospice program?
AB  - The value of integrating palliative with curative modes of care earlier in the
      course of disease for people with life threatening illnesses is well recognized.
      Whereas the now outdated model of waiting for people to be actively dying before
      initiating palliative care has been clearly discredited on clinical grounds, how
      a better integration of modes of care can be achieved, financed and sustained is
      an ongoing challenge for the health care system in general as well as for
      specific institutions. When the initiative comes from a hospital or academic
      medical center, which may, for example, begin a palliative care consultation
      service, financial benefits have been well documented. These palliative care
      services survive mainly by tracking cost savings that can be realized in a number
      of ways around a medical center. We tried to pilot 3 simple models of potential
      cost savings afforded to hospice by initiating a palliative care program. We
      found that simple models cannot capture this benefit (if it in fact exists). By
      adding palliative care, hospice, while no doubt improving and streamlining care,
      is also taking on more complex patients (higher drug costs, shorter length of
      stay, more outpatient, emergency room and physician visits). Indeed, the hospice
      was absorbing the losses associated with having the palliative care program. We
      suggest that an avenue for future exploration is whether partnering between
      hospitals and hospice programs can defray some of the costs incurred by the
      palliative care program (that might otherwise be passed on to hospice) in
      anticipation of cost savings. We end with a series of questions: Are there
      financial benefits? Can they be modeled and quantified? Is this a dilemma for
      hospice programs wanting to improve the quality of care but who are not able on
      their own to finance it?

PMID- 16594407
TI  - Hope: concerning structure and function.

PMID- 16594408
TI  - ACare: a communication training program for shared decision making along a life
      limiting illness.
AB  - OBJECTIVE: This article describes an innovative 8-h training program that
      provides clinicians with the competencies necessary to conduct efficient,
      effective, and compassionate advance care planning discussions throughout the
      trajectory of life-limiting illnesses. METHOD: The Advance Care Training Program
      (ACare) includes 6 h of group workshops and 2 h of one-on-one faculty-learner
      interaction. In this article, we describe the (1) objectives of ACare; (2)
      structure, training procedures, and educational rationale of ACare training; and
      (3) educational outcome studies in progress. RESULTS: ACare training in various
      forms has already been provided to over 100 medical professionals (medical
      students, medical residents, oncology and geriatric fellows, medical attendings,
      social workers, and nurses). Formative outcome data indicate considerable trainee
      satisfaction. Emerging summative outcome data indicate improved skills.
      SIGNIFICANCE OF RESULTS: Widespread adoption of the program could increase the
      frequency and quality of advance care planning discussions between patients with
      life-limiting illnesses, their health care providers, and families.

PMID- 16594409
TI  - Assessing hope at the end of life: validation of an experience of hope scale in
      advanced cancer patients.
AB  - OBJECTIVE: The purpose of this study was to gather validity evidence for an
      innovative experience of hope scale, the Hope Differential-Short (HDS), and
      evaluate its clinical utility for assessing hope in advanced cancer patients.
      METHODS: A consecutive sampling approach was used to recruit 96 patients from an
      inpatient tertiary palliative care unit and three hospice settings. Each
      participant completed an in-person survey interview, consisting of the following
      measures: HDS (nine items), Herth Hope Index (HHI), hope visual analog scale
      (Hope-VAS) and Edmonton Symptom Assessment System (ESAS). RESULTS: Using factor
      analytic procedures, a two-factor structure for the HDS was identified,
      consisting of authentic spirit (Factor I) and comfort (Factor II). The HDS
      factors had good overall internal consistency (alpha = 0.83), with Factor I
      (alpha = 0.83) being higher than Factor II (alpha = 0.69). The two factors
      positively correlated with the HHI, Hope-VAS, and one of the ESAS visual analog
      scales, well-being (range: 0.38 to 0.64) and negatively correlated with
      depression and anxiety, as measured by the ESAS (range: -0.25 to -0.42).
      SIGNIFICANCE OF RESULTS: This is the first validation study of the HDS in
      advanced cancer patients. Its promising psychometric properties and brief patient
      oriented nature provide a solid initial foundation for its future use as a
      clinical assessment measure in oncology and palliative care. Additional studies
      are warranted to gather further validity evidence for the HDS before its routine
      use in clinical practice.

PMID- 16594410
TI  - The Norwegian version of the Herth Hope Index (HHI-N): a psychometric study.
AB  - OBJECTIVE: The purpose of this study was to evaluate the psychometric properties
      of the Herth Hope Index (HHI) in a representative sample of the Norwegian
      population. METHODS: The HHI-N was administered to 4000 people randomly selected
      from the Norwegian population. 1893 questionnaires were usable, yielding a
      response rate of 48.5%. RESULTS: The internal consistency of the HHI-N, estimated
      by Cronbach's alpha, was 0.81. Factor analysis resulted in a two-factor solution,
      which explained 38% of the variance. The correlation between hope and overall
      quality of life was 0.48 (p < 0.001), and between hope and fatigue severity -0.30
      (p < 0.001). SIGNIFICANCE OF RESULTS: Further testing, especially with regard to
      the dimensionality of the instrument, is recommended.

PMID- 16594411
TI  - Giving support and getting help: informal caregivers' experiences with palliative
      care services.
AB  - OBJECTIVE: Palliative care services have made significant contributions to those
      needing end-of-life care, but the effect of these services on informal caregivers
      is less clear. This article reviews the literature and examines the influences of
      palliative care services on caregivers of people who are dying of cancer, HIV
      related illnesses, and illnesses of later life. METHODS: Based on questions that
      we developed from the literature review, we conducted six focus groups in
      Toronto, Thunder Bay, and Ottawa, Canada, with informal caregivers about their
      experiences with caregiving and with palliative care services. RESULTS: We
      outline the major themes relating to the 42 focus group participants' experiences
      of giving support and getting help. SIGNIFICANCE OF RESULTS: Our findings help us
      better understand the common concerns of caregivers of terminally ill seniors,
      people with HIV/AIDS, and people with cancer. The article discusses the
      implications of participants' experiences for palliative care service providers.

PMID- 16594412
TI  - Hospice staff members' views on conducting end-of-life research.
AB  - OBJECTIVE: Hospice staff members have concerns about the appropriateness of
      enrolling terminally ill people in research studies. These concerns can have
      profound implications for the advancement of palliative and hospice care as they
      can impede the empirical investigation of interventions for improving the quality
      of life of patients with advanced disease. This survey study was designed to
      examine hospice staff attitudes, beliefs, and values about research with their
      patients and family members. METHODS: This study utilized a cross-sectional,
      anonymous survey design to measure hospice staff members' beliefs, attitudes, and
      values. The survey contained questions derived by hospice and palliative care
      experts from their experience and review of the literature. It was handed out at
      staff meetings and returned via mail. The survey contained 14 questions and was
      able to be completed in less than 5 min. RESULTS: A total of 225 participants
      (56.25% response rate) completed the survey and were included in the data
      analysis. Hospice staff members were largely supportive about the idea of
      conducting research with patients and family members (mean agreement of 4.08-4.44
      on several perception items about research on a 1-5 scale). They also
      acknowledged a mixture of being protective of controlling access to patients (52%
      wanted to be the ones to approach patients) and not having enough time for
      research (59% either had no time or would be willing to spend no more than 10 min
      on research). SIGNIFICANCE OF RESULTS: Although many of the opinions derived from
      the survey appear to indicate a willingness to embrace research in a hospice
      setting, significant barriers, especially time constraints and protective
      attitudes, remain. Educational efforts and firsthand involvement in the research
      process might be a useful first step in attempting to address these barriers and
      traditionally held beliefs against using hospice patients and families in
      research.

PMID- 16594413
TI  - Care planning for pressure ulcers in hospice: the team effect.
AB  - OBJECTIVE: The standards of care for patients at risk for or with a pressure
      ulcer in hospitals and nursing homes focus on prevention and ulcer healing using
      an interdisciplinary approach. Although not a primary hospice condition, pressure
      ulcers are not uncommon in dying patients. Their management in hospices,
      particularly the involvement of family caregivers, has not been studied. The
      objective of this study is to identify the factors that influence care planning
      for the prevention and treatment of pressure ulcers in hospice patients and
      develop a taxonomy to use for further study. METHODS: A telephone survey was
      conducted with 18 hospice directors of clinical services and 10 direct-care
      nurses. Descriptive qualitative data analysis using grounded theory was utilized.
      RESULTS: The following three themes were identified: (1) the primary role of the
      hospice nurse is an educator rather than a wound care provider; (2) hospice
      providers perceive the barriers and burdens of family caregiver involvement in
      pressure ulcer care to be bodily location of the pressure ulcer, unpleasant wound
      characteristics, fear of causing pain, guilt, and having to acknowledge the dying
      process when a new pressure ulcer develops; and (3) the "team effect" describes
      the collaboration between family caregivers and the health care providers to
      establish individualized achievable goals of care ranging from pressure ulcer
      prevention to acceptance of a pressure ulcer and symptom palliation. SIGNIFICANCE
      OF RESULTS: Pressure ulcer care planning is a model of collaborative decision
      making between family caregivers and hospice providers for a condition that
      occurs as a secondary condition in hospice. A pressure ulcer places significant
      burdens on family caregivers distinct from common end-of-life symptoms whose
      treatment is directed at the patient. Because the goals of pressure ulcer care
      appear to be individualized for a dying patient and their caregivers, the basis
      of quality-of-care evaluations should be the process of care rather than the
      outcome of an incident pressure ulcer.

PMID- 16594414
TI  - Clarifying "meaning" in the context of cancer research: a systematic literature
      review.
AB  - OBJECTIVES: This article synthesizes the published literature related to the
      construct of meaning in the adult cancer population. METHODS: The databases
      CancerLit, CINAHL, Medline, PsychINFO, and the Journal of Psychosocial Oncology
      and PsychoOncology were searched to identify all studies related to meaning. The
      methodological aspects of all studies are described and the conceptual aspects
      are summarized only from those studies that met criteria for methodological rigor
      and validity of findings. The definitions for global meaning, appraised meaning,
      search for meaning, and meaning as outcome as proposed by Park and Folkman were
      used to interpret the findings. RESULTS: Of 44 studies identified, 26 met the
      criteria for methodological rigor. There is strong empirical and qualitative
      evidence of a relationship between meaning as an outcome of and psychosocial
      adjustment to cancer. SIGNIFICANCE OF RESULTS: The qualitative findings are
      considered useful for the development of psychosocial interventions aimed at
      helping cancer patients cope with and even derive positive benefit from their
      experience. However, variations in the conceptual and operational definitions,
      frequent reliance on homogeneous and convenience sampling, and the lack of
      experimental designs are considered to be methodological limitations that need to
      be addressed to advance the study of meaning in the context of cancer.

PMID- 16594415
TI  - Community outreach to patients with AIDS at the end of life in the inner city:
      reflections from the trenches.
AB  - Indigenous community health outreach workers (CHWs), who serve as a bridge
      between underserved, difficult-to-reach minority populations and health
      professionals, can play a critical role in bringing palliative care to patients
      dying of AIDS and other illnesses in the inner city. Although the contribution of
      CHWs in the delivery of "curative" and preventive services has been well
      established, little attention has been given to CHWs in palliative care.
      Integrating the medical literature with experiences of a team providing HIV
      palliative care in the Bronx, a descriptive typology of critical stages and
      components in the work of CHWs in end-of-life care in the inner city is
      presented. A longitudinal case narrative, told from the perspective of the CHW,
      is used to demonstrate the richness and complexity of the CHW's role. The article
      concludes with a description of the experience of the CHW, straddling two worlds-
      the world of the inner city patient and the world of the health care providers-
      and explores the special characteristics of the individuals who can fill this
      vital role in palliative care.

PMID- 16594416
TI  - Brain cancer and sexual health: a case report.
AB  - OBJECTIVE: Cancer patients often encounter sexual concerns during the diagnosing,
      treatment, and recovery phase of their illness. However, the sexual concerns of
      these patients are often overlooked. Brain cancer patients are no exception to
      this oversight. METHODS: A case report of a 39-year-old patient with a history of
      high-grade anaplastic astrocytoma presented to the Sexual Health Program at the
      Memorial Sloan-Kettering Cancer Center complaining of vaginal discharge and
      several months of amenorrhea. Although the patient was administered extensive
      aggressive antineoplastic treatments, her disease rapidly progressed. RESULTS:
      Despite the patient's terminal illness she continued to have normal sexual
      thoughts, feelings, and desires; however, she had difficulty discussing these
      issues with her partner and caregiver, who was her mother. An examination by the
      sexual medicine gynecologist noted no clinical signs of genital infections;
      however, there was minimal vaginal atrophy. Her sexual health laboratory
      evaluation was extensively abnormal. Her treatment consisted of intravaginal non
      hormonal moisturizers and vaginal lubricants, counseling, and sexual education.
      The patient successfully engaged in sexual contact with her partner by the third
      counseling session. SIGNIFICANCE OF RESULTS: Almost all oncology patients have
      sexual concerns during or following cancer treatment. These patients should be
      referred to comprehensive sexual health programs for treatment, if available.

PMID- 16594417
TI  - Living with multiple sclerosis: a spiritual journey of loss.

PMID- 16594418
TI  - Spirituality, meaning, and transcendence.
AB  - End-of-life care provides an opportunity to help a patient find meaning in the
      experience of dying. This is a challenge because the experience of dying can rob
      a patient of meaning. The first step is to look at death as being a process of
      life rather than an event. This is brought about by welding the broken pieces of
      the mind-body connection. Medicine cannot always fix broken pieces, but spiritual
      welding always puts us back together again. Compassionate end-of-life care helps
      a patient connect spirituality with the search for meaning and transcendence.

PMID- 16594419
TI  - Little boy blue.

PMID- 16594420
TI  - "Unintended consequences": can legalizing physician-assisted suicide actually
      result in improved palliative care practices?

PMID- 16594421
TI  - Oregon hospice nurses and social workers' assessment of physician progress in
      palliative care over the past 5 years.
AB  - BACKGROUND: The 1997 enactment of the Oregon Death with Dignity Act intensified
      interest in improving physician education and skills in caring for patients at
      the end of life. OBJECTIVE: To obtain hospice nurse and social workers'
      collateral ratings of efforts made by Oregon physicians to improve their
      palliative care skills over the previous 5 years. DESIGN: A descriptive survey of
      nurses and social workers from all 50 Oregon outpatient hospice agencies.
      MEASUREMENT AND RESULTS: Oregon hospice nurse (N=185) and social worker (N=52)
      respondents, who had worked in hospice for at least 5 years, rated changes they
      observed over the past 5 years in physicians' approach to caring for their
      hospice clients. Six characteristics, including willingness to refer patients to
      hospice, willingness to prescribe sufficient pain medications, knowledge about
      using pain medications in hospice patients, interest in caring for hospice
      patients, competence in caring for hospice patients, and fearfulness of
      prescribing sufficient opioid medications were evaluated. Positive changes were
      endorsed by the majority of respondents on all but the scale measuring
      fearfulness of prescribing opioid medications; on the latter, 47% of nurses rated
      doctors as less fearful, whereas 53% rated them as about the same or more fearful
      than they were 5 years earlier. CONCLUSIONS: Most respondents rated Oregon
      physicians as showing improvements in knowledge and willingness to refer and care
      for hospice patients.

PMID- 16594422
TI  - Knowledge and attitudes toward end-of-life care in veterans with symptomatic
      metastatic cancer.
AB  - OBJECTIVES: The purposes of this study were to study symptomatic metastatic
      cancer patients' knowledge and attitudes toward end-of-life (EOL) care and to
      examine how patient-perceived health status affects attitudes toward EOL care and
      survival. METHODS: From 1999 to 2002, 254 symptomatic metastatic cancer patients
      at the VA New Jersey Health Care System completed the Vermont Voices on Care of
      the Dying Questionnaire. Survival status and location of death were obtained.
      Descriptive statistics and the chi square method were used to assess the
      differences between African Americans (N=109) and Caucasians (N=135), and between
      different patient-perceived health status groups. A log-rank test was performed
      to assess for differences in median survival length between different patient
      perceived health-status groups. RESULTS: Veterans' responses to the Vermont
      questionnaire showed knowledge deficits regarding EOL care. There was wide
      variation in self-rankings of health status: 45.6% of patients rated their
      illness as serious and life threatening, 18.9% considered their health problem
      significant but not life threatening, 2.8% thought they were in good health, and
      one-third of patients were unsure about their health status. Most patients
      (86.2%) preferred physician frankness when communicating bad news and 61.8%
      preferred family involvement in EOL discussions. African American patients were
      less likely to have completed advance directives (p < 0.0001), to have knowledge
      about hospice programs (p < 0.00001), and to feel capable of assessing their
      health situation (p = 0.04). Patient-rated health status affected completion
      rates of advance directives and survival. SIGNIFICANCE OF THE RESEARCH: These
      findings demonstrate knowledge deficits and racial differences in attitudes and
      values toward EOL care in veterans with cancer. The Vermont questionnaire enables
      patients to state their EOL preferences but may not be detailed enough for
      clinical applications. Patient-rated health status may be an important
      explanatory variable for EOL preferences and length of survival.

PMID- 16594423
TI  - Confirmation of the "disability paradox" among hospice patients: preservation of
      quality of life despite physical ailments and psychosocial concerns.
AB  - OBJECTIVE: The purpose of this study was to describe quality of life (QOL) and
      psychosocial and spiritual issues among patients receiving hospice care. METHODS:
      A questionnaire addressing QOL, spirituality, optimism, loss, fears about the
      terminal process and death anxiety was administered to 66 adults receiving care
      from 14 hospices. The physical components of QOL (physical symptoms and physical
      well-being) were rated lower than the psychosocial and spiritual aspects
      (support, existential well-being, psychological symptoms). RESULTS: Respondents
      had a strong spiritual connection and a strong sense of hope. Although these
      individuals did not express anxiety or fear about death, there were concerns
      about the dying process itself. Also, although most felt at ease with their
      current situation, respondents were concerned about how their illness was
      affecting their family. Financial and legal issues did not concern most of these
      individuals. SIGNIFICANCE OF RESULTS: There were few significant associations
      between patient characteristics and the QOL or other psychosocial or spiritual
      issues addressed. Among this older terminally ill population receiving hospice
      care, whose functional status was fair and for whom physical symptoms were
      troublesome, QOL persisted and a positive outlook prevailed.

PMID- 16594424
TI  - Justification for information and knowledge: perceptions of family members in
      palliative home care in Sweden.
AB  - OBJECTIVE: Several studies have concluded that family members in palliative home
      care want information about the patient's disease. The aim of this study was to
      describe family members' perceptions of their motivation for receiving
      information about the patient's disease. METHOD: Semistructured tape-recorded
      interviews were performed with 20 family members of patients with incurable
      progressive cancer who were admitted to hospital-based home care in Sweden. Data
      were analyzed using a qualitative phenomenographic method. RESULTS: Family
      members justified their informational needs by emphasizing that they needed to
      understand and confirm what would happen when the disease progressed, to be
      mentally prepared for the future, to organize their daily life, to be a source of
      information to others, and that receiving information was a natural right.
      SIGNIFICANCE OF RESULTS: This study has revealed some explanations as to why
      family members want information. In clinical practice, it is important that
      palliative care team members are aware of family members' level of knowledge and
      their need for information, as this mental preparation is important.

PMID- 16594425
TI  - Caregiving near the end of life: unmet needs and potential solutions.
AB  - OBJECTIVE: A key aspect of the role of clinicians caring for patients in the
      setting of advanced illness focuses on attending to the needs of informal
      caregivers during the end-of-life period. The purpose of this study was twofold:
      (1) to complement and enrich existing quantitative findings regarding caregiver
      burden near the end of life, and (2) to identify potential solutions to
      caregivers' unmet needs in an effort to assist clinicians in the development of
      clinical interventions. METHODS: This qualitative study, using focus groups and
      content analysis of transcripts, was conducted in a comprehensive cancer center
      in Washington, DC. Seven focus groups were held: three with recently bereaved
      caregivers and four with active caregivers of patients with metastatic cancer and
      an expected survival of 6 to 12 months. RESULTS: Data were stratified into two
      broad categories: (1) general problems and (2) behaviors/activities that were
      helpful/would have been helpful in alleviating these problems. Within each of
      these two categories, five subcategories emerged: medical care (including
      provision of information, coordination of care, bedside manner, satisfaction with
      care), quality of life (including well-being, role adjustments), help from others
      (including practical assistance, social support), positives of caregiving, and
      unsolicited themes (including job flexibility, impact of the disease on the
      family, informational needs, relationship with patient). SIGNIFICANCE OF RESULTS:
      Results suggest caregivers may benefit from more information about patient
      prognosis and hospice, attention to quality-of-life issues, and enhanced, direct
      communication with clinicians. Although information of this nature is likely to
      be known to palliative care clinicians, the specific details and verbal insights
      provided by caregivers give an important voice to existing quantitative data and
      may provide more detailed information to assist palliative care clinicians
      seeking to develop interventions to meet caregiver needs during the period near
      the end of life.

PMID- 16594426
TI  - Human relationship: the forgotten dynamic in palliative care.
AB  - OBJECTIVE: Palliative care is a philosophy of care for individuals experiencing
      progressive, incurable disease. It encompasses two dynamics, science-based
      practice and relationship between patient, family, and health professional. Each
      dynamic is essential for quality palliative care, yet the requisites for each are
      different. METHODS: The scientific process of observation and measurement
      requires differentiation, distance, and detachment to fulfill its demands for
      objectivity, whereas relationship, unobservable and immeasurable, requires
      sameness, closeness, and connection of a shared humanity. It is science, however,
      the prevailing world-view, that shapes our thinking and consequently, influences
      the education and practice of health professionals. RESULTS: We explore the
      dynamics of science and relationship and the incongruities between them. We
      examine the prominence of science in palliative care and its impact on
      relationship. SIGNIFICANCE OF RESULTS: We contend that questioning the current
      emphasis of science in palliative care and discovering the joy and rewards of
      shared human experience will enrich the quality of life for patients, families,
      and health professionals.

PMID- 16594427
TI  - Complementary and alternative medicine in breast cancer patients.
AB  - OBJECTIVE: Complementary and Alternative Medicine (CAM) is becoming increasingly
      popular among cancer patients, in particular those with breast cancer. It
      represents one of the fastest growing treatment modalities in the United States.
      Therefore, knowledge of CAM therapies is becoming necessary for physicians and
      other health care providers. CAM encompasses a wide range of modalities including
      special diet and nutrition, mind-body approaches, and traditional Chinese
      medicine. METHODS: We reviewed the biomedical literature on CAM use in breast
      cancer patients, using Medline search from 1975 until 2002. In addition,
      consensus reports and books on CAM and breast cancer were included in the review.
      We evaluated the prevalence of CAM use in breast cancer patients, the reasons
      cited for its use, the different available modalities, and the reported outcomes.
      RESULTS: Use of CAM in breast cancer patients ranges between 48% and 70% in the
      United States. The most commonly used CAM modalities include dietary supplements,
      mind-body approaches, and acupuncture. The reasons cited for using CAM were to
      boost the immune system, improve the quality of life, prevent recurrence of
      cancer, provide control over life, and treat breast cancer and the side effects
      of treatment. Several studies reported favorable results including improved
      survival, better pain control, reduced anxiety, improvement in coping strategies
      and significant efficacy in treating nausea and vomiting. Other less well
      organized trials have reported either no benefit or negative effect of CAM and
      potential toxicity of some commercial products. SIGNIFICANCE OF RESULTS: CAM is a
      growing field in health care and particularly among breast cancer patients.
      Knowledge of CAM by physicians, especially oncologists, is necessary. Oncologists
      should be willing to discuss the role of CAM with their patients and encourage
      patients to participate in well-organized research about CAM.

PMID- 16594428
TI  - Suicidal ideation at end-of-life: the palliative care team's role.
AB  - OBJECTIVE: To report on the case of a terminally ill patient who expresses
      suicidal ideation. METHODS: As this case demonstrates, suicidality at end-of-life
      poses numerous challenges for the palliative care team. In this case, a 49-year
      old man with locally extensive head and neck cancer refused all life-prolonging
      treatment and expressed a desire to hasten his own death. Other issues, such as
      chemical dependency and lack of social supports, complicated his care. RESULTS:
      Suicidality lessened as continuity of care, with ongoing assessments and
      interventions, addressed sources of suffering and built relationships with health
      care professionals. SIGNIFICANCE OF RESULTS: This case highlights the observation
      that desire for hastened death fluctuates for patients at end-of-life and may be
      influenced by factors under the control of the palliative care team.

PMID- 16594429
TI  - Pulling the plug.

PMID- 16594430
TI  - What do our patients want and need? A palliative care clinician's view from the
      trenches.

PMID- 16594431
TI  - Courage: the heart of the matter.

PMID- 16594432
TI  - Spouse caregivers of terminally-ill cancer patients as cancer patients: a pilot
      study in a palliative care unit.
AB  - OBJECTIVE: It is known that families of terminally-ill cancer patients show
      levels of emotional and functional disruption and are called "second order
      patients," however, little is actually known about the health problems of family
      members, especially in terms of cancer. METHODS: This study reviewed the family
      histories of terminally-ill cancer patients in a palliative care unit and
      investigated cancer related health problems of the spouses of terminally-ill
      cancer patients. RESULTS: We investigated the past medical history of 125 spouses
      of terminally-ill cancer patients and found that five spouses had a past medical
      history of cancer. In these five spouses, the duration of illness, present status
      of treatment and physical condition were reviewed from the database. Of these
      five spouses, three patients continued to attend an outpatient clinic regularly
      for checkup and one patient was hospitalized for nephrectomy. Two spouses did not
      have physical symptoms that made them unable to provide direct care for the
      terminally-ill spouses, while three could not provide care because of their own
      physical symptoms derived from cancer. SIGNIFICANCE OF RESULTS: Our findings
      indicated that some of the spouses of terminally-ill cancer patients are not only
      "second order patients" but also "cancer patients." Our findings also suggest
      that some spouses of terminally-ill cancer patients might experience distress
      both as a cancer patient and as a spouse and may need care both as a cancer
      patient and as a spouse.

PMID- 16594433
TI  - Assessing symptoms of terminally-ill patients by different raters: a prospective
      study.
AB  - OBJECTIVE: For patients who are terminally ill, the efficiency of symptom
      management is dependent, among other factors, on an accurate assessment by proxy
      raters. The aim of this prospective study is to describe differences in symptom
      severity ratings between patients and their nurses, physicians, and family
      members during their stay in different departments with acute care, and to
      identify variables associated with the accuracy of the ratings by others.
      METHODS: Physical, psychological, social, and functional disorders were assessed
      for 41 in-patients with a standardized 13-item Symptom List for Quality Assurance
      in Palliative Care drafted by the Working Group on the Core Documentation for
      Palliative Care Units in Germany. Symptom assessment was completed by different
      raters (patient, nurse, physician, family member) within the first four days
      after admission. Socio-demographic, disease-related, and hospitalization data
      were taken from patient charts. RESULTS: Reliability of the symptom list was
      computed with Cronbach's alpha measures for the present sample. Between-group
      comparisons on the individual items and on the sum-score level were analyzed
      separately for the different rater-pairs: patients-nurses (n = 41), patients
      physicians (n = 39), patients-family members (n = 12). Multiple regression
      analyses calculated predictive variables of the staff's deviation scores.
      SIGNIFICANCE OF RESULTS: Significant differences for nurses and physicians were
      found on the sum-score level for psychological and social symptoms, but not for
      physical and functional symptoms. Family members rated the intensities of the
      symptoms generally higher than the patients. Suggestions for further analyses are
      presented and discussed.

PMID- 16594434
TI  - Depression in patients with advanced illness: an examination of Ontario complex
      continuing care using the Minimum Data Set 2.0.
AB  - OBJECTIVE: In this study, we examined the prevalence of depression, its
      recognition, and its treatment in continuing care patients with advanced illness
      (AI). METHODS: All data were obtained from the Ontario (Canada) provincially
      mandated MDS 2.0 form for chronic care. Of 3,801 patients, 524 met our empiric
      definition of AI, which was predicated on a previously validated algorithm. The
      MDS-embedded Depression Rating Scale (DRS) was used to measure psychological well
      being and a score of 3 or greater indicated potential depression. RESULTS: Twenty
      nine percent of patients with AI scored greater than 3, making them nearly twice
      as likely to be potentially depressed as other patients (OR 1.8, 95% CI 1.5-2.2).
      Despite this patients with AI were less likely to have received antidepressants
      (28.9% vs. 38.2%), even among those with a diagnosis (45.3% vs. 58.4%). Using
      logistic regression, correlates of potential depression were identified and
      surprisingly patients with cancer were substantially less likely to be depressed
      (AOR 0.37, 95% CI 0.2-0.6). Further investigation revealed that cancer patients
      were more likely to be treated for depression and to be recognized as being
      within the terminal phase of illness. SIGNIFICANCE OF RESULTS: These findings
      suggest that a high proportion of terminally ill patients had unmet needs for
      psychological support. As well, they suggest that cancer patients received better
      targeted end-of-life care, which resulted in an overall decrease in psychological
      distress when compared to other patients with similarly advanced illness.

PMID- 16594435
TI  - Preparation of residents for death pronouncement: a sensitive and supportive
      method.
AB  - OBJECTIVE: To identify factors associated with internal medicine interns' self
      assessed competency in death pronouncement and to evaluate the effectiveness of a
      10-minute death pronouncement module and pocket card guidelines. METHODS: In June
      2003 at the Birmingham VAMC, Alabama, 48 internal medicine interns completed a
      survey of medical school education, training, and experience in death
      pronouncement and a self-assessment of death pronouncement competency. In
      September 2003, 33 of the 48 interns completed a follow-up training/education
      survey and rated their post-intervention competency. Using chi-square and paired
      t-tests, we identified factors associated with variations among baseline and post
      intervention variables and examined pre-post changes in self-assessed competency
      levels. RESULTS: At baseline, less than 30% of the interns had medical school
      instruction in the process of death pronouncement. More than 70% reported needing
      basic instruction/close supervision. Post-intervention, close to 90% interns
      needed minimal or no assistance. Over 50% reported using pocket card guidelines.
      We found significant pre-post increases in mean rankings in each of the 5 self
      assessed competencies (p < .001). Factors associated with differences in baseline
      and post-intervention assessments included medical school training/experience and
      use of the pocket card guidelines. SIGNIFICANCE OF RESULTS: When interns began
      training, most had no instruction in death pronouncement and felt unprepared for
      this task. With brief instruction, pocket card guidelines, and 3-months
      experience, the majority of interns reported needing minimal/no assistance in
      pronouncing death. A larger sample from multiple sites is needed to confirm these
      findings.

PMID- 16594436
TI  - Factors associated with location of death of children with cancer in palliative
      care.
AB  - OBJECTIVE: The aim of this study was to identify factors associated with location
      of death of patients receiving palliative care in a pediatric oncology unit.
      METHODS: A palliative care program was developed in the pediatric department in
      order to provide specialized attention to the patient and family in end-of-life.
      The program is coordinated by a nurse, delivering a simultaneous
      interdisciplinary team approach with focus on identification and training of a
      family care provider as well as local resources supplemented by support of a
      social worker and the community. All 87 patients in palliative care were followed
      by the team. The factors associated with the location of death (home or hospital)
      were evaluated for the 71 patients who died prior to analysis. RESULTS: Forty-two
      (59%) patients died at home. Factors significantly associated with dying at home
      were: male with an Odds Ratio (OR) = 3.80, 95% Confidence Interval (CI) = 1.26
      11.76; public health insurance (OR) = 4.95, 95%[CI] = 1.03-26.75, low educational
      level of the caregiver (OR) = 11.11 95%[CI] = 1.65-94.66 and low educational
      level of the mother (OR) = 7.07 95%[CI] = 1.37-40.14. Gender was the only
      independent factor associated with location of death: a boy had a higher risk of
      dying at home, (OR) = 4.25, 95%[CI] = 1.37-13.21 when compared to a girl.
      SIGNIFICANCE OF RESULTS: In our society we are still not able to provide hospice
      care or home care for all children, although increasing emphasis has been placed
      on utilizing local resources. Even though we had increased the number of desired
      home deaths, it is still a challenge to meet patients and families' requests. A
      team approach, the recognition of the factors involved, and adequate health and
      community support have helped us to meet the child and family's needs.

PMID- 16594437
TI  - A specialist nurse-function in neurooncology: a qualitative study of
      possibilities, limitations, and pitfalls.
AB  - OBJECTIVE: Brain tumors, a cancer that affects the cortical processes, have a
      substantial social impact. Typically, malignant glioma is a brain tumor with a
      poor prognosis; few patients survive more than two years after diagnosis. In the
      last several years, different groups have documented how this disease affects a
      patient's quality of life. These findings have resulted in new ways for nurses to
      improve the care for these patients and their spouses. However, these initiatives
      have not been studied in a systematic way. This study investigates how patients
      with malignant glioma and their families respond to a special nurse, a nurse
      specifically instructed to address the needs of the patient and the patient's
      family. METHODS: Sixteen patients and their next-of kin were included. At the
      time of diagnosis, the special nurse offered to serve as a resource to the
      patient and the patient's family. During the whole course of the disease, the
      nurse recorded her interactions with the patients and the patients' family. In
      addition, the spouses were interviewed after the patient's death. Data was
      analysed qualitatively with focus on tasks and relationships. RESULTS: Four
      relationships between the special nurse and the family were detected: 1) a
      resource for the whole family; 2) a parallel resource within the family; 3) a
      resource for the next-of kin; and 4) a resource for the patient. Most of the
      patients and their families found this program beneficial. The nurse provided the
      patient and family with several functions. In some cases the family and nurse
      interaction developed into a closer relationship, a relationship based on the
      nurse's availability and concern for the patient's and family's welfare.
      SIGNIFICANCE OF RESULTS: This close relationship underlines the importance of the
      nurse's professionalism and a systemic perspective for understanding the nurse's
      function within the milieu of a cancer patient's family.

PMID- 16594438
TI  - Family decision making at end of life.
AB  - OBJECTIVE: To enhance understanding of the phenomenon of family surrogate
      decision-making at the end of life (EOL) by means of a systematic review and
      synthesis of published research reports that address this phenomenon. METHODS:
      Garrard's (1999) methods for conducting a systematic review of the literature
      were followed. Fifty-one studies focusing on family decision-making experiences,
      needs, and processes when assisting a dying family member were selected following
      electronic database searches and ancestry searches. RESULTS: In studies using
      hypothetical scenarios to compare patients' choices and surrogates' predictions
      of those choices, surrogates demonstrated low to moderate predictive accuracy.
      Increased accuracy occurred in more extreme scenarios, under conditions of forced
      choice, and when the surrogate was specifically directed to use substituted
      judgment. In qualitative explorations of their perspectives, family members
      voiced their desire to be involved and to accept the moral responsibility
      attendant to being a surrogate. Quality of communication available with providers
      significantly influenced family satisfaction with decision-making and EOL care.
      Group or consensual decision-making involving multiple family members was
      preferred over individual surrogate decision-making. Surrogates experienced long
      term physical and psychological outcomes from being decision-makers. SIGNIFICANCE
      OF RESULTS: Functioning as a surrogate decision-maker typically places great
      moral, emotional, and cognitive demands on the family surrogate. Clinicians can
      provide improved care to both patients and families with better understanding of
      surrogates' needs and experiences.

PMID- 16594440
TI  - We tend to forget some of the work with wire that was published when
      veterinarians were only just beginning.

PMID- 16594439
TI  - Professionalization of hospice volunteer practices: what are the implications?

PMID- 16594441
TI  - Interlocking nail treatment of long-bone fractures in cats: 33 cases (1995-2004).
AB  - A retrospective study between 1995 and 2004 of fracture repair in cats (n = 46)
      using interlocking nails (ILN) was made. Only the cases in which clinical and
      radiographic examination of bone healing were available are included. Five
      humeral and twenty eight femoral fractures were reviewed. Multiple-hole
      interlocking nails (MH-ILN) were used in 22 fractures, with the four-hole model
      (FH-ILN) in the remaining cases. In three of the cases, the FH-ILN was
      transformed to a three-hole model by cutting the nail between the two most distal
      holes. The average length of humeral ILN was 78.8 mm, and the femoral ILN was
      97.2 mm. Static fixation was performed in 27 cases, with dynamic fixation in the
      remaining. The medullary canal filling was 100% in both radiographic views in 16
      cases. Intra-operative complications were encountered in two cases. A total
      number of 76 screws were inserted, with 5.26% of them being malpositioned.
      Malunion, in a deformed femur, and partial unscrewing of one screw were the only
      radiographic complications observed at the time of follow-up. The clinical
      outcome, as well as fracture healing, were excellent in all of the cases. The
      results of this study indicate that the 4.0 and 5.0 mm MH-ILN and FH-ILN can be
      used to repair simple or comminuted humeral and femoral fractures in cats.

PMID- 16594442
TI  - Evaluation of different techniques for percutaneous needle biopsy of synovial
      membrane in the dog.
AB  - Four different needles were evaluated for percutaneous needle biopsy (PNB) of the
      synovial membrane (SM) in six different joints (carpus, tarsus, elbow, shoulder,
      stifle, hip) from eight dog cadavers. Needle biopsies were retrieved with the
      Parker-Pearson (PP), a novel modified Parker-Pearson (PPM), the Tru-Cut (TC), and
      the Franklin-Silverman (FS) needles. The success rate of PNB to produce biopsies,
      of adequate histological quality, was assessed for each needle type and joint.
      The joints were subsequently surgically opened and standard open SM biopsies were
      harvested from an adjacent area. The articular cartilage was inspected and graded
      for damage caused by PNB sampling. The length of the intact synovial lining cell
      layer (SLCL) and the histological quality of the needle biopsies were compared to
      the open surgical biopsies. Success rates for the different needles were 49.2%
      (PPM), 37.5% (PP), 26.7% (TC), and 1.7% (FS). The highest success rates were
      achieved in the carpus and stifle; the lowest success rate was found in the hip
      joint. The intact SLCL from the PNB samples was an average of 3.4 times shorter
      than that of the surgical biopsies. The proportion of the samples with adequate
      histological quality was 81% for open surgical biopsies and 62% for PNB samples.
      The FS was found to produce the highest incidence of articular cartilage damage.
      The application of PNB for SM sampling is a valuable alternative to the open
      surgical biopsy in dogs. Modifications of the Parker Pearson needle by Arassy and
      Schumacher and novel modifications introduced by the authors, offer encouraging
      results, and merit further clinical and research investigations.

PMID- 16594443
TI  - A comparison of palpation guided and ultrasound guided percutaneous biceps
      brachii tenotomy in dogs.
AB  - The purpose of this study was to compare palpation guided and ultrasound guided
      techniques for biceps brachii tenotomy in dogs. The differences between the two
      tenotomy procedures in muscle incision length, confidence level of tenotomy,
      percentage tendon transection, difficulty of tendon location or transection, or
      amount of haemorrhage, were not significant. The ultrasound guided tenotomy
      procedure took significantly longer to perform and required a longer skin
      incision, but these differences were not considered to be clinically important.
      With palpation guided tenotomy, several surrounding muscular and tendinous
      structures were damaged. We concluded that ultrasound guided tenotomy is an
      accurate method of tendon identification because it allowed for complete
      transection in 10 out of 11 tendons, and provides a method for checking
      completeness of tendon transection after the procedure.

PMID- 16594444
TI  - Effect of durotomy on functional outcome of dogs with type I thoracolumbar disc
      extrusion and absent deep pain perception.
AB  - Spinal cord durotomy is performed as a diagnostic aid in determining spinal cord
      structural integrity, and this may be useful as an indicator of prognosis in
      cases with loss of deep pain perception (DPP). It has been suggested that a
      durotomy may relieve intramedullary compression but there is some debate about
      the therapeutic value. The purpose of this study was to compare ambulatory
      outcome of dogs that had loss of DPP treated with hemilaminectomy with durotomy
      versus hemilaminectomy without durotomy. Medical records of 81 dogs diagnosed
      with type I thoracolumbar IVD were reviewed. Dogs were included in the study if
      DPP was absent upon initial neurological examination and surgical decompression
      via hemilaminectomy was performed. Of the 81 cases, 48 were included in this
      study. The number of dogs that recovered ambulatory function were compared
      between durotomy and non-durotomy groups with a chi-squared test (p < 0.05). No
      differences were found. The findings of this study suggest that durotomy is
      useful as a diagnostic modality and that performing a durotomy does not
      significantly affect post-operative recovery of voluntary motor function.

PMID- 16594445
TI  - The evaluation of extracorporeal shockwave therapy in naturally occurring
      osteoarthritis of the stifle joint in dogs.
AB  - Extracorporeal shockwave therapy (ESWT) has expanded from the original uses of
      human urinary calculi treatment to veterinary orthopaedic applications. This
      paper investigates the feasibility and efficacy of treating dogs with
      osteoarthritis of the stifle joint with ESWT. In this study, dogs with persistent
      stifle lameness despite previous surgical or medical treatment were either
      treated with ESWT or served as untreated controls. The more lame rear limb of
      each dog was determined by force platform analysis. The range of motion (ROM) of
      the stifle joints was assessed by goniometry. Force platform gait analysis and
      goniometry were performed on both groups for four visits at three-week intervals
      and a final examination four weeks later. Shock wave therapy was performed three
      times on the treated dogs, once at each of the first three examinations. A
      placebo treatment consisting of clipping and wetting the hair was performed on
      the control dogs. The vertical forces were evaluated for objective analysis of
      treatment response. For peak vertical force (PVF), four of seven treated dogs
      improved, while only one of five of control dogs improved. The PVF for the within
      group analysis did not show any significant change for the treated group,
      however, the control group has a significant decrease (p = 0.05) in PVF
      consistent with an increase in lameness. The range of motion (ROM) of the stifle
      joint improved in five of seven treated dogs and three of five controls. Dogs in
      the treated group had a trend toward increased ROM (p = 0.07) and a 'positive
      slope' when compared to dogs in the control group which did not have a
      significant change (p = 0.78) and had a negative slope indicating the dogs were
      developing a decrease in ROM. The subjective data provided by client
      questionnaire did not show significant difference between groups.

PMID- 16594446
TI  - Effects of three intramedullary pinning techniques on pin location and articular
      damage in the canine humerus.
AB  - The purpose of this study was to compare the pin location and articular damage
      for intramedullary (IM) pins inserted into the humerus in a directed retrograde,
      non-directed retrograde, and normograde fashion. Proximal pin positioning in the
      humerus was significantly more cranial (p < 0.05) using both retrograde
      techniques when compared to the normograde technique, although this did not cause
      significant interference with anatomical structures. The distance to the biceps
      tendon, transverse humeral ligament, and the distal pin location was similar with
      all insertion techniques, however two of ten pins passed in a non-directed
      retrograde fashion penetrated the shoulder joint. The results of this study
      suggest that although non-directed retrograde pinning cannot be recommended,
      either normograde or retrograde pins directed craniolaterally provide acceptable
      techniques for insertion of IM pins during distal humeral fracture repair.

PMID- 16594447
TI  - Evaluation of healing in feline femoral defects filled with cancellous autograft,
      cancellous allograft or Bioglass.
AB  - Cancellous bone grafting is a widely accepted technique in human and veterinary
      orthopaedic surgery. However, the use of autogenous bone graft is limited by the
      additional surgical time required to harvest the graft, the morbidity associated
      with the donor site, and the limited availability of cancellous bone, especially
      in feline patients. Various allografts and bone graft substitutes are available
      commercially but have not been fully evaluated for efficacy in the cat. The
      purpose of this study was to compare the incorporation of autogenous and
      allogenous cancellous bone graft and Bioglass, a synthetic bone graft substitute,
      in femoral defects in cats. Four (4.0 mm diameter) defects were created in the
      lateral diaphyseal cortex of the left femur with an orthopaedic drill. In each
      femur, one of the cortical defects was filled with autogenous cancellous graft
      (harvested from the tibia), one was filled with allogenic cancellous graft, and
      one was filled with Bioglass. The fourth defect remained unfilled. Graft
      incorporation within the femoral defects was evaluated by radiographic evaluation
      every two weeks. Six weeks after the grafting procedure, the cats were
      euthanatized and high detailed radiography, dual energy X-ray absorptiometry
      (DEXA), histopathology and histomorphometry of the defects were performed.
      Satisfactory bone healing was observed within all of the defects.

PMID- 16594449
TI  - Performance of a composite flow moulded carbon fibre reinforced osteosynthesis
      plate.
AB  - Non-metallic implants have the advantage over metallic implants of reduction in
      artefact with CT and MR diagnostic imaging. In-vivo performance of a carbon fibre
      reinforced polyetheretherketone radiolucent plate (Snake Plate [SP]) with high
      stiffness, and fixed angle converging screws was compared with a seven-hole
      titanium Locking Compression Plate (LCP), using a sheep tibial osteotomy model
      (gap 0.6 mm). The sheep were divided into two groups, and the osteotomies were
      stabilized with a SP (n = 6) or a LCP (n = 6). The callus dimensions were
      measured radiographically at zero, two, four, six and eight weeks. The animals
      were euthanatized after eight weeks. Osteotomised and contralateral tibiae were
      tested in pairs torsion, to determine strength and stiffness. In the radii of six
      separate sheep, initial vascular disturbance after plate implantation was
      evaluated. All of the sheep of the SP and LCP groups showed maximal callus areas
      at six weeks. The differences between the groups, in callus dimension, were not
      significant at any time point. The median values for relative reduction (100 x
      [operated contralateral] / contralateral) in strength of osteotomized tibiae was 
      13.93% for the SP group and -7.49% for the LCP group (p = 0.5228), and for
      stiffness it was -24.44% for the SP group and -27.08% for the LCP group (p =
      0.6481). Neither the SP nor LCP caused any notable disturbance in periosteal
      circulation. The SP appears to represent a valuable alternative to metallic
      implants for shaft fracture repair. The main advantages of the SP are
      radiolucency, high deformation resistance, internal fixator concept and
      converging screw configuration for optimal loading conditions in the bone-implant
      construct.

PMID- 16594448
TI  - Examination of synovial fluid and serum following intravenous injections of
      hyaluronan for the treatment of osteoarthritis in dogs.
AB  - A randomized, blinded, prospective clinical trial was performed to determine the
      effects of intravenous (i.v.) administration of hyaluronan sodium (HA) on serum
      glycosaminoglycans (GAG) concentrations, synovial fluid (SF) hyaluronan
      concentrations and viscosity in dogs treated for unilateral rupture of the
      cranial cruciate ligament. Twenty-two dogs undergoing tibial plateau leveling
      osteotomy were used in this study. Synovial fluid from both stifles and serum
      were collected prior to surgery and at 2, 4, and 8 weeks following surgery. Dogs
      received either 1.0 ml (10 mg) of sodium hyaluronate (treatment group 1; n = 10)
      or equal volume of 0.9% NaCl (treatment group 2; n = 12), i.v. immediately, 2 and
      4 weeks following surgery. Synovial fluid viscosity was evaluated using a
      magnetically driven, acoustically tracked, translating-ball rheometer. Synovial
      fluid HA disaccharide content was measured by fluorophore-assisted carbohydrate
      electrophoresis. Serum GAG concentrations were measured by alcian blue
      spectrophotometric assay. Data were analyzed using a Wilcoxon sign rank test (p <
      0.05). Mean +/- SD viscosity (cP) was significantly higher (p = 0.011) in SF
      obtained from the intact stifle (450 +/- 604.1) than injured (54.8 +/- 60.8)
      prior to surgery. Mean +/- SD HA concentrations (ug/ml) were significantly higher
      (p = 0.02) in synovial fluid obtained from the injured stifles (281.4 +/- 145.9)
      than intact stifles (141.6 +/- 132.5). No significant difference was noted within
      or between treatment groups in SF viscosity, HA concentrations, or serum GAG
      concentrations at any time following surgery. Stifles with cranial cruciate
      ligament insufficiency had significant alterations in SF viscosity and HA
      concentrations.

PMID- 16594450
TI  - Effect of starting distance on vertical ground reaction forces in the normal dog.
AB  - The purpose of this study was to evaluate the effect of starting distance on the
      peak vertical force (PVF) and associated vertical impulses (VI) of normal dogs.
      Five dogs of similar weight and body type were trotted at a velocity of 1.6-2.2
      m/s from each of three starting distances; 2, 4, and 6 m, from the first plate in
      a two plate test field. A total of ten trials were recorded from each starting
      distance, five left first contacts and five right first contacts. Each ground
      reaction force (GRF) of interest was evaluated both within and between the three
      starting distances using a complete block ANOVA. There was not any significant
      effect of distance found on peak vertical forces in our study. However, distance
      did affect VI. Forelimb VI generated at a 2 m trot was significantly less than VI
      generated at a 6 m trot. Neither extreme distance was found to be significantly
      different than the 4 m VI. The VI of the hind limb was not significantly
      affected.

PMID- 16594451
TI  - Spinal epidural abscess in a juvenile dog.
AB  - A six-month-old, intact female, Miniature Pinscher was admitted with signs of
      progressive neurological deficits in the hind legs, an elevated rectal
      temperature, and spinal pain of 48 hours duration. A myelogram was performed
      which demonstrated a dorsal, left sided compressive lesion extending from T11
      T13. A left-sided hemilaminectomy was performed from T11-T13. A friable, poorly
      organized, pale tan and red mass was identified within the epidural space.
      Cytopathological and histopathological analyses of the mass demonstrated marked,
      subacute, suppurative cellulitis. A culture of the purulent material revealed
      beta haemolytic Streptococcus sp.

PMID- 16594452
TI  - Multiple cartilaginous exostosis in a Golden Retriever cross-bred puppy.
      Clinical, radiographic and backscattered scanning microscopy findings.
AB  - Multiple cartilaginous exostosis was diagnosed in a six-month-old Golden
      Retriever cross-bred male with a history of forelimb lameness and isolated, but
      very painful, acute episodes. Physical examination revealed a right forelimb
      lameness with a firm, painful palpable mass on the cranial aspect of the forearm.
      The radiological examination showed the presence of bony masses at the humerus
      and radius as well as several masses in the ribs and spinous processes of the
      thoracic vertebrae. Based on the history and radiographic findings, multiple
      cartilaginous exostosis was diagnosed. Treatment with non-steroidal anti
      inflammatory drugs was commenced for two weeks without any effect. Due to the
      lack of a response to the treatment as well as to the progressive physical
      deterioration of the animal, the owners requested euthanasia of the dog.
      Histology of the different exostoses demonstrated the presence of a hyaline
      cartilage cup surrounding a central area, formed mainly by bone and cartilage
      trabecullae. Signs of malignancy were not observed. Back-scattered scanning
      electron microscopy (BEI-SEM) study revealed well ordered and progressively
      calcified cartilage trabecullae present underneath the non-calcified cartilage
      cap. At a greater depth, those cartilage trabecullae became osteochondral
      trabecullae, and the innermost were formed exclusively by woven and lamellar
      bone. The histological and back-scattered electron scanning microscopy results
      conclude that it was a well-arranged normal endochondral ossification process
      that followed a centripetal pattern inside the bony mass, confirming the
      diagnoses of multiple cartilaginous exostoses.

PMID- 16594453
TI  - Locking compression plate fixation of radial and tibial fractures in a young dog.
AB  - A six-month-old, male Bernese Mountain Dog in which radius-ulna and tibia-fibula
      concomitant fractures were treated each with a 3.5 mm Locking Compression Plate
      (LCP) is presented. Both fractures were approached and plated medially. The
      tibial fracture had to be revised with a 4.5 mm intramedullary nail and a new 3.5
      mm LCP at the second post-operative day because of fixation breakdown. The follow
      up radiographs taken at days 14 and 53 revealed uneventful healing of both
      fractures. Implants were removed 53 days after surgery.

PMID- 16594455
TI  - Cruising for a bruising.

PMID- 16594454
TI  - God and science: can we believe in both?

PMID- 16594456
TI  - Reducing the risk of burnout in end-of-life care settings: the role of daily
      spiritual experiences and training.
AB  - OBJECTIVE: Individuals in the helping professions are subject to unique stressors
      that may lead to burnout, and research has shown that those who work with dying
      or bereaved individuals might be particularly at-risk. This study explores how
      factors such as spirituality and level of training might buffer the stress of
      working with terminally ill clients and their families. METHOD: A total of 80
      medical and mental health practitioners attending palliative care seminars were
      surveyed, with each completing validated measures of daily spiritual experiences
      and caregiver burnout, as well as assessments of demographic factors, their
      general education and training experiences specific to working in end-of-life
      care and bereavement settings. RESULTS: Findings indicate that daily spiritual
      experiences might mitigate physical, cognitive, and emotional forms of burnout in
      the workplace. In addition, a negative correlation was found between the amount
      of end-of-life training received and burnout in the physical and cognitive
      domains. However, training was not related to professionals' level of emotional
      exhaustion. SIGNIFICANCE OF THE RESEARCH: Results reinforce a growing literature
      on the salutary effects of spirituality, and underscore its relevance as one
      possible form of constructive coping for professionals attending to the needs of
      the dying and bereaved. The study carries further implications for how the
      stresses of such work might be ameliorated by enhanced training efforts, as well
      as creative facilitation of diverse spiritual expressions (e.g., inclusive forms
      of ritual recognition of loss) in the workplace.

PMID- 16594457
TI  - Does ethnicity matter? Bereavement outcomes in two ethnic groups living in the
      United Kingdom.
AB  - BACKGROUND: Sociologists, anthropologists, and psychologists agree that grief is
      a universal phenomenon. Reactions to it are, however, socially constructed and
      patterned. OBJECTIVE: To compare the outcomes of bereavement among family or
      close friends of deceased first-generation black Caribbean and white native-born
      patients living in the United Kingdom. DESIGN: Comparative cross-sectional
      questionnaire survey in three inner London health authorities administered 10
      months after the patient's death. PARTICIPANTS: Family and close friends of 50
      deceased first-generation black Caribbean and 50 native-born white patients with
      advanced disease. MAIN OUTCOME MEASURES: 28-item General Health Questionnaire
      (GHQ-28), Core Bereavement Items scale, a 17-item measure of grief. RESULTS: The
      intensity of grief, measured using the Core Bereavement Items was similar between
      the two groups. Seventy-two respondents had visited their family doctor
      subsequent to bereavement, and of these, black Caribbean respondents reported
      more psychological problems. Depression and anxiety measured by the GHQ-28 were
      significantly higher among black Caribbean respondents (28.00 vs. 21.2) (t-test =
      -2.28, p = 0.025). Multiple regression analysis revealed this difference was best
      accounted for by bereavement concerns such as legal and housing problems.
      CONCLUSIONS: This study has observed higher psychological morbidity among the
      bereaved Caribbean individuals. Family doctors are a source of support for three
      quarters of respondents, and they may need to focus on the needs of black and
      minority ethnic minorities.

PMID- 16594458
TI  - Health-related quality of life and enrollment in phase 1 trials in children with
      incurable cancer.
AB  - OBJECTIVES: To investigate health-related quality of life (HRQOL) in children
      eligible for Phase 1 trials and the reasons why families consider participating
      in these trials. METHODS: Individual, semistructured interviews were conducted
      with parents (seven mothers, two fathers) and three children, after a child was
      invited to participate in a clinical trial. Information regarding disease and
      treatment progression, daily life, and decision making about experimental
      treatments was elicited. Interviews were recorded, transcribed, and coded for
      themes. RESULTS: HRQOL themes were grouped into four main domains: physical,
      psychological, social, and spiritual. Minimal physical restrictions, maintaining
      normalcy and control, information sharing, and having hope for life seemed to be
      critical HRQOL components. Hope for a cure and prolonging the child's life were
      the main reasons for enrolling in Phase 1 trials. CONCLUSIONS: Normalcy and
      control are key end-of-life HRQOL components, and hope for life is a main reason
      for participating in Phase 1 trials.

PMID- 16594459
TI  - The impact of a multidimensional exercise program on self-reported anxiety and
      depression in cancer patients undergoing chemotherapy: a phase II study.
AB  - Little is known about the role of exercise in improving cancer patients' mood
      while undergoing chemotherapy. In this phase II study changes in self-reported
      anxiety and depression and fitness (VO2max) are reported in relation to a 6-week,
      9 h weekly, multidimensional exercise program. A total of 91 patients receiving
      chemotherapy, between 18 and 65 years old, completed a Hospital Anxiety and
      Depression Scale Questionnaire (HADS; response rate 91%, adherence rate 78%).
      Anxiety (p < 0.001) and depression (p = 0.042) was significantly reduced. The
      mean +/- SD of the change was -1.14 +/- 2.91 for anxiety and -0.44 +/- 2.77 for
      depression. Improvements in fitness were correlated with improvements in
      depression, chi2(1) = 3.966, p = 0.046, but not with improvements in anxiety,
      chi2(1) = 0.540, p = 0.462. The research suggests that exercise intervention may
      have a beneficial impact on psychological distress for cancer patients receiving
      chemotherapy with low to moderate levels of baseline psychomorbidity. The study
      furthermore indicates that changes in distress may be associated with disease
      status and levels of physical activity undertaken during disease. The study is
      followed up by an ongoing randomized clinical controlled trial to evaluate
      potential causal effects of exercise intervention on psychological distress and
      fitness in cancer patients undergoing chemotherapy.

PMID- 16594461
TI  - Attitudes of oncologists toward euthanasia in Turkey.
AB  - There have been intensive debates about euthanasia and attempts to change laws on
      euthanasia in all countries. What doctors and particularly oncologists think
      about euthanasia must be taken into consideration, as their voices are crucial in
      this dialogue. The aim of this study was to find out how Turkish doctors approach
      euthanasia in the context of cancer. A questionnaire was used to collect data
      from 85 oncologists out of a total 800 in active oncology practice. Of the
      oncologists surveyed, 43.8% did not object to euthanasia. Some 33.7% had been
      asked to perform euthanasia and 41.5% believed that euthanasia was performed
      secretly although it is against the law in Turkey. Forty-two doctors (50.6%)
      noted that they had withdrawn treatment in patients. Doctors who encounter
      terminally ill patients with cancer should update their knowledge about patients'
      rights and euthanasia. Doctors, who are often asked to perform euthanasia,
      especially in the cancer setting, can help to illuminate the debates about
      euthanasia.

PMID- 16594460
TI  - Outcome expectations and self-regulation in cancer patients: reliability, initial
      factor structure, and relationships with benefit finding.
AB  - OBJECTIVE: The purpose of this research was to investigate outcome expectation
      and self-regulation measures within a sample of cancer patients and to explore
      relationships of these variables with benefit finding. The outcome expectation
      and self-regulation measures were evaluated for reliability and initial factor
      structure. METHOD: A convenience sample of 141 cancer patients completed study
      measures while waiting for appointments at a cancer center. RESULTS: The measures
      demonstrated good reliability (alphas = .88 and .92, for outcome expectation and
      self-regulation respectively). Initial factor structure suggested six outcome
      expectation factors (managing symptoms, expressing emotions, talking about
      cancer, learning about cancer, managing self-image, and managing needs) and one
      self-regulation factor. Gender and treatment status were related to outcome
      expectations but not self-regulation. Outcome expectations and self-regulation
      were significant predictors of benefit-finding, F(8, 80) = 3.1, p = .005.
      SIGNIFICANCE OF THE RESEARCH: Measures of outcome expectations and self
      regulation are reliable, are related to gender and clinical variables, and may be
      useful as predictors of cancer patients' ability to find benefits in their cancer
      experience.

PMID- 16594462
TI  - Atypical antipsychotics in the management of delirium: a review of the empirical
      literature.
AB  - OBJECTIVES: To review the existing literature of atypical antipsychotics in the
      treatment of delirium and make recommendations regarding their use in the
      treatment of delirium. METHODS: I conducted a literature search in Pubmed,
      Psychlit, and Embase for studies using atypical antipsychotics in the treatment
      of delirium. In the absence of studies, case reports were used. RESULTS: Overall
      13 studies examined the use of risperidone, olanzapine, and quetiapine, two cases
      were reported about ziprasidone, and no publication was found using aripiprazole
      in the treatment of delirium. Among the existing studies were retrospective and
      prospective, open label studies in addition to one with a double blind design
      using risperidone. Risperidone, olanzapine, and quetiapine may be all similarly
      effective in the treatment of delirium, whereas there may be limited efficacy in
      the use of olanzapine in the hypoactive subtype of delirium in elderly
      populations, which may generalize to the other atypical antipsychotics. The use
      of atypical antipsychotics in the treatment of delirium is safe and carries a low
      burden of side effects. SIGNIFICANCE OF RESULTS: Although atypical antipsychotics
      are widely used in the treatment of delirium, well-designed studies do not exist.
      Among the existing studies, stronger data supports the use of risperidone and
      olanzapine, and also quetiapine may be considered in the treatment of delirium.
      Recommendations are made based on the existing data and literature. The need for
      well-designed studies to validate the use of atypical antipsychotics in the
      treatment of delirium continues.

PMID- 16594463
TI  - Death and dying: implications for inpatient, psychiatric care.
AB  - Under a traditional medical model, discussion of issues related to death and
      dying are usually avoided with clients who hold a psychiatric diagnosis. Too
      often the result is that individuals in inpatient, psychiatric facilities are
      left to face grief without emotional or spiritual support. With its focus on the
      individual, family, and community involvement, and fostering independence, the
      psychosocial model affords an opportunity to change how mental health
      professionals address the topic of death. In this article the authors give
      practical suggestions for working with clients who are dying or who have
      experienced the death of a loved one. Two case studies are used to illustrate how
      these ideas can be translated into action.

PMID- 16594464
TI  - Proactive: spiritual care for terminal restlessness.

PMID- 16594465
TI  - [Characteristics of psychological factors participating in the etiopathogenesis
      of primary arterial hypertension of children and adolescents].
AB  - The article presents summary of psychological examination of patients with the
      primary arterial hypertension disease who where hospitalized in the Department of
      Pediatric Cardiology of Silesian Medical University in Katowice. All results were
      analyzed in comparison with actual literature related to discussed problem-
      participation of psychosocial factors in the development of arterial
      hypertension. Psychological tests were performed for 60 patients between 9 and 18
      years old. Selected group was analyzed on the following agents: sociodemographic
      data, intra-familial relations, level ofneuroticism, alexithymia, external and
      internal irritation, Behavioral pattern "A", learning achievements and data
      related to selected elements of lifestyle. The choice of above variables comes
      from their importance of illness' etiopathogenesis in literature. Achieved
      results proved theoretical expectations about selected group specification. They
      also showed the necessity of taking primary arterial hypertension referring to
      children and adolescents in psychosocial context of diagnostic and therapeutic
      assumptions.

PMID- 16594466
TI  - [Cavernous angiomas in the Department of Neurosurgery in Katowice].
AB  - 166 patients with arterio-venous malformations (AVM) were treated in the
      Department of Neurosurgery at Silesian School of Medicine from 1987 to 2002.
      There were 30 (18%) patients diagnosed as cavernous angioma (CA). The oldest
      treated patient was 73 years old and the youngest one was 5 years old. 16 (55%)
      male and 14 (45%) female were examined and the results of this examination are
      presented below. The location of CA was as follows: supratentorially--19 patients
      (64%), infratentorially--6 patients (20%), extracranially--5 patients (16%).
      During the admission the clinical status of patients were evaluated according to
      Glasgow Coma Scale (GCS) and Hunt-Hess scale (H-H). Epilepsy occurred in 5
      patients (16%), neurological focal deficits--14 (45%), intracranial hemorrhage--7
      (23%). All patients were examined using CT (computer tomography) scan, cerebral
      angiography was carried out in 15 (50%) patients and MRI (magnetic resonance
      imaging) in 16 (55%). All patients were operated on in our medical centre. The
      results of treatment were presented according to Glasgow Outcome Scale (GOS).

PMID- 16594467
TI  - [Primary extranodal non-Hodgkin's malignant orbital lymphomas treated surgically
      in ENT Department of Medical Academy of Silesia in Katowice in the years 1996
      2001].
AB  - The authors presented 7 cases of primary extranodal non-l-odgkin's malignant
      orbital lymphomas in patients treated surgically in the ENT Department of the
      Medical University of Silesia in the years 1996-2001. In the course of the
      diagnostic process we examined the patients carefully to be sure that the cancer
      had not disseminated. We used some imaging techniques such as: ultrasonography
      (USG), computer tomography (CT) and magnetic resonance imaging (MRI). We also
      used the needle aspiration biopsy, as an additional examination. However the
      material was no significant in the most cases and we were unable to make a
      definitive diagnosis on the basis of this method alone. After prior examinations
      we performed the radical operations and removed the tumors. In each case the
      postoperative material was examined using histopatological and
      immunohistochemical methods. Afterwards the pathomorphological diagnosis was made
      by the specialists. Next the patients were observed and treated in the
      Haematological and Radiotherapy Departments.

PMID- 16594468
TI  - [Metabolic syndrome in obese children].
AB  - The aim of the study was to evaluate the incidence of metabolic syndrom's
      abnormalities in obese children and family risk factors. MATERIAL AND METHODS: We
      examined 280 (M/F 127/153) children in the age of 14.2 +/- 2.5 years with obesity
      duration 9.4 +/- 4.1years. The control group consisted of 70 (M/F 31/39)
      normostenic children matched according to age and stage of puberty. RESULTS: In
      the group of children with obesity, family history (I and/or IInd degree
      relatives) of: obesity was stated in 78.0%, hypertension 42.9% and diabetes
      mellitus type 2 in 44.6%, all these three risk factors together were present in
      16.3%. Abdominal adiposity was noted in 66.8% (WHR > or = 0.9/0.85),
      hyperinsulinemia 0'(> or = 20 microUI/ml) in 30.7%, I/G (> or = 0.30
      microUI/l/mg%) in 22.9%, IGT in 13.2%, fasting hyperglycemia (6.1-7.1 mmol/l)-
      5.4%; serum lipids (mmol/l): Ch-T (> or = 4.81) - 43.2%; LDL-Ch (> or = 2.6) -
      62.5%; HDL-Ch (< or = 0.9) - 51.4%; TG (> or = 1.7) - 30.4%. Hypertension (>
      130/85) in 6.4%. Metabolic syndrome (of three or more abnormalities) was stated
      in 50% children with abdominal adiposity. CONCLUSIONS: (1) Metabolic syndrome is
      present in obese children. (2) Current literature and our own study indicate the
      necessity of early prevention through constant education of correct nutrition and
      physical activity.

PMID- 16594469
TI  - [Corticosteroid phobia in patients with atopic dermatitis].
AB  - Topical corticosteroid phobia is an interesting phenomenon recently mentioned
      often in the literature. It is characterized by an irrational fear and anxiety of
      patients about using topical corticosteroid preparations and may be associated
      with confusion and lack of knowledge regarding potency and indications for use of
      various groups of these widely used in dermatological practice topical drugs. So
      called "steroid phobia" may be additionally augmented by media. The aim of this
      study was to investigate the problem of corticosteroid phobia in atopic
      dermatitis (AD) patients, attending Allergic Diseases Diagnostic Center of the
      Department of Dermatology, University of Medical Sciences in Poznan. The study
      revealed confusion and anxiety among the AD patients about topical corticosteroid
      therapy. More than half of AD patients felt uncertain about using topical steroid
      preparations and had little knowledge regarding their potency and side effects,
      especially in case of drugs used less frequently. One of the most important
      sources of information about corticosteroids was doctor's consultation. It seems
      that proper education of patients provided by health care staff might improve
      clinical efficacy of treatment and patients' compliance.

PMID- 16594470
TI  - [Efficacy of combination therapy with interferon-alpha and ribavirin for chronic
      hepatitis C in relation to liver fibrosis and serum aminotransferase activity].
AB  - The aim of the study was to evaluate the efficacy of interferon alpha (IFNalpha)
      2b in combination with oral ribavirin for treatment of chronic hepatitis C in
      relation to age, sex, liver enzymes activity as well as to grading and staging of
      liver disease in histologic examination. There were 154 adult patients assigned
      for the retrospective analysis including 69 females and 85 males of 16 to 70
      years of age (mean age 43.3 +/- 12 years) treated with IFNalpha and ribavirin for
      24 or 48 weeks. Sustained virological response was achieved in 66 patients
      (42.9%) and sustained biochemical response rate was 44%. Sustained response
      correlated with younger age, lower baseline AST, GT and ALP activities as well as
      with lower staging of liver disease. Combination treatment with interferon and
      ribavirin was significantly more effective in patient under 40 years of age and
      in patients without cirrhosis. Sex, baseline ALT activity and histological
      grading of liver disease did not differ between sustained responders and non
      responders. Sustained virological response on combination therapy was achieved in
      5 out of 7 previous monotherapy relapsers (71.4%) whereas only 5 patients out of
      22 monotherapy non-responders benefited from combination therapy (22.7%). In
      conclusion, efficacy of combination therapy with IFNalpha and ribavirin in
      patients with liver cirrhosis is less effective and should be considered in
      chosen situations, especially in younger patients. Normal ALT activity should not
      be an exclusion criterion to therapy. Combination retherapy in previous
      monotherapy non-responders seems to be ineffective whereas in monotherapy
      relapsers good sustained response can be achieved.

PMID- 16594471
TI  - [Prognostic value of the initial response to corticosteroids for children with
      acute lymphoblastic leukemia].
AB  - Leukemias are the most common malignant diseases in childhood, with acute
      lymphoblastic leukemia (ALL) being the most frequent subtype. Diagnosis and
      treatment of ALL remains an important issue in pediatric practice. The great
      variety of prognostic factors has been recognized and applied for the
      stratification into different risk groups and consequently for selection of the
      most appropriate treatment. The most significant prognostic factors include age,
      sex, white blood count at diagnosis, infiltration of the extramedullary organs,
      and central nervous system involvement. The experience of numerous pediatric
      hemato-oncology centers has shown that above-mentioned prognostic criteria are
      not sufficient and they emphasize the need for determination of the response to
      glucocorticosteroids at day 8 of treatment. A retrospective analysis of treatment
      results in childhood in ALL patients with regard to steroid response has been
      performed. The study aimed at analysis whether there is any association between
      the long-term event-free survival (EFS) in patients with good and poor response
      to prednisone. The study group consisted of 179 children, aged 2 to 17 years,
      qualified into low and medium risk groups, treated according to the BFM-86 and
      BFM-90 protocols in the Department of Pediatrics and Hematology of Silesian
      Center of Pediatrics in Zabrze between 1986 and 1996. In the study group, 89.9%
      (161) of children showed good prednisone response (PGR) as compared to 10.1% of
      children with poor response to steroids (PPR). Cumulative probability of 15-year
      EFS for the PGR group was 70% and significantly differed from EFS in PPR group
      (39%; p = 0.006). In the study group, the children showing good response to the
      initial treatment with prednisone have higher chance for durable remission and
      subsequent cure. In conclusion, response to glucocorticosteroids employed in the
      initial treatment of children with ALL, should be included in the stratification
      into prognostic groups.

PMID- 16594472
TI  - [Laparoscopic cholecystectomy--the method of choice in the elderly].
AB  - The aim of the study was the comparison and assessment of the results of
      gallbladder excision performed with the classical and laparoscopic methods in
      persons after age of 70. A total of 242 patients with mean age of 76.1 years
      operated on in the years 1999-2002, were analysed. 150 of them were operated with
      the laparoscopic and 92 with the classical methods. The frequency of
      postoperative--surgical and general--complications and the presence of
      concomitant diseases associated with old age were compared. Laparoscopic
      procedures are distinguished for an almost six fold decrease in the percentage of
      complications (6 vs. 35%) loaded comparably with concomitant diseases. Patients
      operated with laparoscopic methods had suffered from cardiac infarctions twice as
      often in their past history (17 vs. 8%). The method of laparoscopic gallbladder
      excision proved to be beneficial also in persons of advanced age.

PMID- 16594473
TI  - [The results of cytogenetic investigations in 107 couples with recurrent
      spontaneous abortions from Pomerania-Kujawy region of Poland].
AB  - About 10-15% of clinically diagnosed pregnancies end by spontaneous abortion. One
      of the causes of recurrent abortions is the presence of chromosome aberrations in
      a parent. The paper presents the results of cytogenetic investigations in 107
      couples referred to genetic council clinic because of at least 2 spontaneous
      abortions. Cytogenetic analysis was performed on peripheral blood lymphocytes
      after standard 72h PHA-stimulated culture. At least 20 GTG- and CBG-banded
      metaphases were analyzed in each patient. Fluorescence in situ hybridization
      technique was used as to precisely define cytogenetic results. Chromosome
      aberrations were found in 7 couples (6.54%), exclusively in women. Numerical
      aberration (47,XXX) was present in 1 woman, and balanced structural aberrations
      in 6 (5.61%). In 3 of them balanced translocations were disclosed: t(7;
      19)(p13;p13.3), t(8;16)(q24;q22), and t(3;8)(q21;p21), in 2--inversions:
      inv(2)(p25q31), inv(17)(p12p13.3), and in 1--der(20). Pericentric inversion of
      chromosome 9 was found in 3 men. The analysis of nongenetic factors showed that
      neither age, nor congenital anomalies of uterus could be an important factor
      causing abortions in analyzed couples with aberrations. However, infections and
      muta- or teratogenic exposure could contribute to loss of pregnancies in some
      cases. Authors conclude that karyotype analysis should be an integral part of
      diagnostics in couples with recurrent abortions.

PMID- 16594474
TI  - [CT colonography--a new method in the diagnosis of the colon].
AB  - CT colonography--the method of examination of the colon with spiral computed
      tomography--was presented. Examination technique, its clinical application and
      current position among other diagnostic examinations of the large bowel, as well
      as further development of the method were described.

PMID- 16594475
TI  - [Medical applications of probiotics].
AB  - Normal microflora of the digestive tract plays an important role in maintaining
      competence of the immune system. Imbalance of the flora may lead to the
      development of either diseases related to overgrowth of its selected constituents
      (post-antibiotic diarrhoea, travellers' diarrhoea or infection by external
      pathogens--rotavirus diarrhoea) or diseases resulting from altered immunological
      response (atopy, inflammatory bowel disease, neoplasmas). It is believed that
      application of probiotics may restore proper composition and functions of the
      microflora and thus bring new perspectives into prevention and treatment of these
      illnesses. Prospective studies on mechanisms of the probiotic activities may
      enable their new medical applications.

PMID- 16594476
TI  - [Pathomechanism of cachexia in chronic obstructive pulmonary disease].
AB  - Weight loss is a characteristic for advanced chronic obstructive pulmonary
      disease (COPD), but its mechanism remains unexplained. The decrease of lean body
      mass is due to a negative energy balance with a noncatabolic hypermetabolic
      state. Pulmonary inflammation or tissue hypoxia might contribute to it, the
      decrease in protein content is accompanied by an increase in reactive oxygen
      forms. Tumor necrosis factor (TNF) has been implicated, other candidates are
      cytokines IL-1B and IL-6. Activation of apoptosis may be noticed. Pulmonary
      inflammation and changes in serum leptin may be interrelated. Other hormonal
      disturbances involve serum IGF-1 level decrease, increase of insulin resistance,
      raised catecholamine and cortisol levels and other mechanisms which need further
      investigations. Up to now the attempts undertaken to counteract the observed
      hormonal changes failed to success.

PMID- 16594477
TI  - [Clinical usefulness of gastric tonometry in anesthesiology and intensive care
      medicine].
AB  - Gastric tonometry is relatively non-invasive technique to assess gastric
      perfusion and to monitor oxygen metabolism in visceral system. The technique
      utilizes the PCO2 of the gastric fluid to calculate intramucosal pH (pHi). The
      calculation is assessed by a modified Henderson-Hasselbalch equation. The
      combination of a high intramural PCO2 and mucosal acidosis may result from
      decreased splanchnic perfusion. The values of pHi and regional PCO2 (PrCO2) based
      on gastric tonometry reflect indirect index of visceral blood flow. In clinical
      practice the PCO2 of the gastric fluid is collected from saline sampled in the
      penetrable by carbon dioxide balloon. The silicon balloon is a part of tonometric
      probe placed in the gastric lumen. Device TONOCAP (Datex-Ohmeda, Helsinki,
      Finland) allows for full automatic measurement of the carbon dioxide regional
      pressure (PrCO2). Presented experimental and clinical studies confirmed the
      usefulness of gastric tonometry in visceral blood perfusion assessment during
      perioperative and critical ill stage. Finally, the technique allows to decrease
      the number of complications, treatment expenses and mortality.

PMID- 16594478
TI  - [Sexual dysfunctions induced by antidepressive agents].
AB  - Sexual dysfunctions may be one of depressive symptoms as well as undesirable
      effects of some antidepressive agents' application. The article presents
      pathophysiological mechanisms connected with the influence of antidepressive
      drugs on particular stages of sexual reaction. Authors also presented drug
      strategies in cases of sexual dysfunctions as their spontaneous relief is rather
      a rare phenomenon.

PMID- 16594480
TI  - [The role of tumor necrosis factor (TNF-alpha) in control of metabolism].
AB  - Tumor necrosis factor is multifunctional cytokine involved in various cell
      functions, such as differentiation, mitosis, angiogenesis, inflammation and
      immune controls. TNF-alpha plays also an important role in the control of
      metabolism. Its action on adipocytes includes increasing secretion of
      triglicerydes and inhibiting insulin action, controlling expression of some genes
      and modulating free fatty acid and leptin secretion. The review of the current
      literature on the TNF-alpha role in metabolism is presented in this paper.

PMID- 16594479
TI  - [Clinical application of anagrelide as a selective inhibitor of megakaryocyte
      system].
AB  - Anagrelid is, in our country, comparatively a new compound selectively affecting
      the megakaryocyte line in bone marrow leading to its reversal inhibition,
      simultaneously showing some exceptional, interesting pharmacological features.
      Essential trombocythemia, being a sole indication for the drug administration, is
      one of the chronic myeloproliferative disorders which exposes individuals to
      significantly increased risk for thrombohaemorrhagic complications. Regarding the
      latest literature data, the most present therapeutic modalities in this disease
      were presented focusing the interest on anagrelid being, in majority of cases,
      the drug of choice in uncontrolled megakaryocyte proliferation. The drug
      therapeutic value and characteristics were presented on the background of another
      compounds regarded as standard therapeutic options for essential thrombocythemia.

PMID- 16594481
TI  - [Diaschisis phenomenon in different neurological diseases].
AB  - Diaschisis is based on reversible depression of functions anatomically or
      functionally connected to the damaged area. It was described for the first time
      in 1914 by von Monakow. There has been a rise in the studies on diaschisis over
      the past twenty years--what is closely related to the progress made in functional
      neuroimagining techniques. In this article we try to describe the diaschisis
      phenomenon, its types, the possibilities of its investigations and clinical
      implications.

PMID- 16594482
TI  - [Some aspects of gallbladder carcinogenesis].
AB  - Gallbladder carcinoma is an uncommon but highly malignant tumor with a poor
      survival rate. The coincidence of gallstones, especially those with a diameter
      over 3 cm and gallbladder carcinoma is well established. Anomalous junction of
      pancreaticobiliary ducts (AJPBD) is an additional risk factor for gallbladder
      malignancy. Those conditions followed by chronic inflammation lead to many
      molecular disturbances in the cell cycle of the gallbladder mucosa and make the
      tumorigenesis possible.

PMID- 16594483
TI  - [The choice of anesthesia in Hallervorden-Spatz disease].
AB  - The authors presents some clinical and histochemical problems in Hallervorden
      Spatz disease (HSD) and a suggestion about the choice of anesthesia in a teenage
      women qualified to dental sanitation. All suggestions were based on literature
      references and kinetic parameters of used anesthetics. The safety and practical
      analysis of TIVA were underlined.

PMID- 16594484
TI  - [Family incidence of Addison-Biermer anemia].
AB  - Addison-Biermer anemia is an autoimmune disease with genetic predisposition. It
      is more common in families of the patients with pernicious anemia and other
      immune diseases. We present two cases of family incidence ofA-B anemia. In our
      opinion precise taking of family history is very important for the treatment and
      prevention of Addison-Biermer anemia.

PMID- 16594485
TI  - [Myocardial infarction in 16-year-old boy].
AB  - Myocardial infarction (MI) is a condition with serious prognosis which depends on
      many factors. Despite the considerable progress in the treatment of MI in
      children and teenagers, it is still a reason for concern for cardiologist due to
      the young age of the patients. The author presents the case of 16 years old boy
      diagnosed with MI and treated in Cardiology Department in Sanok, Poland. The
      author paid attention to excessive physical activity in a patient with elevated
      blood pressure and positive family history. Lack of parents' consent for coronary
      angiography did not able to reveal the true reason of MI. Based on literature
      data, negative result of stress test and the result of myocardial perfusion
      scintigraphy, muscle bridge in the left anterior descending artery was assumed
      the probable cause of MI.

PMID- 16594486
TI  - [Lichen sclerosus et atrophicus].
AB  - A case of 43-year-old woman with skin and genital lesions of lichen sclerosus et
      atrophicus was presented. It was paid attention to simultaneously examination of
      the skin and genital areas. For this reason it is necessary closed cooperation
      between dermatologists and gynaecologists for determination of proper diagnosis.

PMID- 16594487
TI  - [DDD pacemaker implantation during atrial fibrillation in a patient with
      persistent left superior vena cava].
AB  - The case of 65-year-old male patient who underwent DDD pacemaker implantation due
      to symptomatic tachy-brady syndrome with first degree AV block is presented.
      During the procedure a paroxysmal atrial fibrillation occured and the presence of
      persistent left superior vena cava (PLSVC) was diagnosed. The "straight" passive
      fixation leads were introduced through the PLSVC and placed in the right atrium
      and ventricle, using curved stylets. Atrial lead implantation during atrial
      fibrillation is discussed. At three month, a follow-up revealed normal DDD
      pacemaker function.

PMID- 16594488
TI  - [Immunotherapy in aplastic anaemia as a cause of reactivation of hepatitis B
      virus-immunologic aspects].
AB  - We present history of 16-year-old boy, HBsAg carrier, treated with interferon
      alpha at the age of 6 because of hepatitis B (HBeAg/antyHBe seroconversion). In
      August 2002--admitted to Department of Pediatric Oncology due to pancytopenia-
      diagnosis of severe aplastic anaemia was made (bone marrow cellularity--10%). We
      found no relative donor for hematopoietic cells transplantation and started
      immunosuppresive therapy (ATG, G-CSF, methyloprednisolon, cyclosporin).
      Haematologic parameters were improving. At day +60 he was admitted to our
      Department due to the increase in aminotransferases and cyclosporin activity. He
      was treated with cefuroxim, acyclovir and drugs improving liver cell function,
      cyclosporin was stopped. Presence of HBV DNA in serum confirmed HBV reactivation-
      a boy received lamivudine and cyclosporin again (as a maintenance therapy of
      aplastic anaemia). Aminotransferase activity and haematological parameters
      returned to normal. This case indicates the possibility of HBV reactivation in
      the course of immunosuppressive therapy (e.g. after antithymocytic globulin and
      cyclosporin) for aplastic anaemia.

PMID- 16594489
TI  - [Typhoid fever with atypical manifestation in a 5-year-old boy].
AB  - Nowadays in Poland, Salmonella typhi (S. typhi) infections are diagnosed rare.
      Despite the low incidence of typhoid fever, this disorder should be still in our
      mind. The clinical profiles of typhoid fever are various and atypical
      manifestation often makes the serious diagnostic problem, in childhood
      especially. We report herewith a case of typhoid fever in 5 years old boy,
      manifested as a respiratory tract infection. We present also some basic
      information on this rare but still serious disorder and on Gram-negative bacilli
      identified as S. typhi causing the typhoid fever.

PMID- 16594490
TI  - [Central European Congress on Osteoporosis and Osteoarthrosis. 13th Congress of
      The Polish Society of Osteoarthritis and Polish Foundation of Osteoporosis.
      Krakow, October 6-8, 2005].

PMID- 16594491
TI  - Familiar sights. Design team takes its cues from the local community.

PMID- 16594492
TI  - Cold comfort. Is your cooling tower ready for summer?

PMID- 16594493
TI  - What to know about JCAHO. Joint Commission survey process changing this year.

PMID- 16594494
TI  - Planning for the worst. Is your emergency facility ready for epidemics and
      special-risk patients?

PMID- 16594495
TI  - Waste watch. A model for managing discarded pharmaceuticals.

PMID- 16594496
TI  - Volunteer: give 'til it feels good!

PMID- 16594497
TI  - Dental assistant apprenticeship program within the U.S. Disciplinary Barracks.

PMID- 16594498
TI  - Alternative to veneers.

PMID- 16594499
TI  - Deja vu all over again?

PMID- 16594500
TI  - Are RHIOs for real?

PMID- 16594501
TI  - Smart phones finding voice in health care. Though adoption still is low, new
      health care applications are evolving for the converged devices.

PMID- 16594502
TI  - Are cards finally a good bet? There's no consensus on whether smart cards have a
      role to play in an increasingly connected industry.

PMID- 16594503
TI  - Linux knocking at the back door. The platform makes some inroads with servers,
      but has a ways to go on the front end.

PMID- 16594504
TI  - Payers using I.T. to give and receive. Health plans help docs automate and
      increase electronic ties to patients.

PMID- 16594505
TI  - I.T. asked to read the fine print. Delivery system uses contract management
      application to uncover millions in underpayments.

PMID- 16594506
TI  - Suite spot provides interesting views. Telemedicine links and electronic records
      enable docs to treat rural, urban and international patients.

PMID- 16594507
TI  - Group finds App within App. A specialty practice is happy to 'inherit' web-based
      claims management software.

PMID- 16594508
TI  - EKG + E-records equals efficiencies. Group practice saves time, paper after
      wirelessly integrating EKG devices with its records system.

PMID- 16594509
TI  - EMR goes on a lengthy assignment. A long-term care organization brings together
      clinical and financial software to reduce the paper form glut and improve
      efficiency.

PMID- 16594510
TI  - Technologies improve care in first minutes. New systems give doctors and
      ambulance crews more upfront information that can help save lives.

PMID- 16594511
TI  - Web site helps drive bottom line. In-depth medical content helps hospital
      increase online traffic and patient volume.

PMID- 16594512
TI  - Stress and its impact on healthcare workers.

PMID- 16594513
TI  - Counting on efficiency. Healthcare organizations in growth mode need financial
      information systems that can accommodate expansion.

PMID- 16594515
TI  - Diving for data. A southwest Florida hospital deploys clinical and financial
      analysis tools to eliminate losses and empower decision makers.

PMID- 16594514
TI  - Gentlemen--start your engines. When healthcare IT collaborates with hospital
      marketing, increased profitability is just one of many potential benefits.

PMID- 16594516
TI  - Paean to process. Tennessee hospital lab's dedication to process improvement
      culminates in patient identification system that streamlines the specimen
      collection process and reduces errors.

PMID- 16594518
TI  - Prepare and share: the community hospital's path to NHIN. Now is the time for
      community hospitals to plan for a future with nationwide interoperability.

PMID- 16594517
TI  - (Good) growing pains. Michigan ED automates patient tracking, nurse documentation
      and charge capture to maintain excellent customer service, increase efficiencies
      and boost revenue.

PMID- 16594519
TI  - All-out outsourcing. A Virginia community hospital uses outsourcing the way
      Fortune 100 companies do.

PMID- 16594520
TI  - Take-along tech and the training of specialty nurses. A unique program to foster
      nursing recruitment and retention puts PDAs and point-of-care medical references
      into nurses' hands.

PMID- 16594521
TI  - Why are we worried about denials management?

PMID- 16594522
TI  - Composting: a potentially safe process for disposal of genetically modified
      organisms.
AB  - The widespread use of genetically modified organisms (GMOs) may result in the
      release of GMOs into the environment. The potential risks regarding their use and
      implementation of disposal methods, especially the possibility of novel genes
      from GMOs being transferred to natural organisms, need to be evaluated and better
      understood. There is an increasingly accepted public view that GMO products
      introduced into the environment should be degradable and should disappear after a
      limited period of time. Due to the risk of possible horizontal gene transfer,
      disposal methods for GMOs need to address destruction of both the organism and
      the genetic material. During the last two decades, we have developed a greater
      understanding of the biochemical, microbiological and molecular concepts of the
      composting process, such that maximum decomposition may be achieved in the
      shortest time with minimal negative impacts to the environment. The conditions
      created in a properly managed composting process environment may help in
      destroying GMOs and their genes, thereby reducing the risk of the spread of
      genetic material. When considering composting as a potential method for the
      disposal of GMOs, the establishment of controlled conditions providing an
      essentially homogenous environment appears to be an important requirement. An
      evaluation of composting as a safe option for disposal of GMOs is provided in
      this review.

PMID- 16594523
TI  - Near infrared spectroscopy for bioprocess monitoring and control: current status
      and future trends.
AB  - The development of Near Infrared Spectroscopy has paralleled that of the PC, and
      the application of NIR in many industries has undergone explosive growth in
      recent years. This has been particularly apparent in the area of microbial and
      cell culture system monitoring and control. Potentially, NIR offers the prospect
      of real-time control of the physiology of cultured cells in fermenters, leading
      to marked improvements in authenticity, purity and production efficiency. Despite
      this, NIR is not yet as widely applied within the bioprocessing industry as its
      potential might suggest. This review critically evaluates the development of this
      rapidly moving area as it pertains to microbial and cell culture system control
      and highlights the critical stages in the development of the technology. It
      indicates the work that must still be carried out if the full potential of NIR is
      to be exploited in making proteins, hormones and antibiotics by the fermentation
      route. The review comes at a particularly timely moment when NIR stands on the
      threshold of widespread acceptance in bioprocessing. This is the ideal moment to
      assess what the technology can offer the microbiologist, and where it may develop
      in the future.

PMID- 16594524
TI  - Microbial CO conversions with applications in synthesis gas purification and bio
      desulfurization.
AB  - Recent advances in the field of microbial physiology demonstrate that carbon
      monoxide is a readily used substrate by a wide variety of anaerobic micro
      organisms, and may be employed in novel biotechnological processes for production
      of bulk and fine chemicals or in biological treatment of waste streams. Synthesis
      gas produced from fossil fuels or biomass is rich in hydrogen and carbon
      monoxide. Conversion of carbon monoxide to hydrogen allows use of synthesis gas
      in existing hydrogen utilizing processes and is interesting in view of a
      transition from hydrogen production from fossil fuels to sustainable (CO2
      neutral) biomass. The conversion of CO with H2O to CO2 and H2 is catalyzed by a
      rapidly increasing group of micro-organisms. Hydrogen is a preferred electron
      donor in biotechnological desulfurization ofwastewaters and flue gases.
      Additionally, CO is a good alternative electron donor considering the recent
      isolation of a CO oxidizing, sulfate reducing bacterium. Here we review CO
      utilization by various anaerobic micro-organisms and their possible role in
      biotechnological processes, with a focus on hydrogen production and bio
      desulfurization.

PMID- 16594525
TI  - Hospitals save millions on VAP with oral care program.

PMID- 16594526
TI  - Needle prices level off.

PMID- 16594527
TI  - The final grains of wisdom.

PMID- 16594528
TI  - Oops! It happened again!

PMID- 16594529
TI  - Bridging the gap. Crest Smile Shoppe brings oral care to underserved children.

PMID- 16594531
TI  - State of the state. ISDS House defeats dues increase, passes deficit budget.

PMID- 16594530
TI  - Split decision. It's win some, lose some for 8th District in 2005 House.

PMID- 16594532
TI  - Playing the percentages of life.

PMID- 16594533
TI  - Going to the dogs.

PMID- 16594534
TI  - Bringing up baby's teeth.

PMID- 16594535
TI  - Feeling no pain.

PMID- 16594536
TI  - Mortui vivis praecipant.

PMID- 16594537
TI  - Review of the literature: elbow incongruity in the dog.
AB  - Elbow incongruity is the term to describe bad alignment of the joint surfaces of
      the elbow. Two features illustrate incongruity of the elbow: an abnormal shape of
      the ulnar trochlear notch and a step between the radius and ulna, caused by
      either a short radius or a short ulna. It has been suggested that both an
      elliptical notch, and a step, can cause increased local pressure within the
      joint, resulting in loose fragments at different locations: ununited anconeal
      process (UAP), fragmented coronoid process (FCP), osteochondritis dissecans of
      the humeral condyle (OCD). These lesions are grouped under the term 'elbow
      dysplasia' and are the most frequent causes of front leg lameness in the dog.
      Although several radiographic features to diagnose incongruity have been
      described, the 'scoring' of incongruity is subjective because there is currently
      no objective method to measure the degree of incongruity. Because superimposition
      is avoided, CT is suggested as a standard technique to measure incongruity.
      Arthroscopy on the other hand, allows the direct visualisation of the intra
      articular structures and their abnormalities. Information on both techniques are
      still relatively new. Several surgical techniques have been proposed to restore
      joint congruity; the one most frequently used is an ulnar osteotomy. But because
      of possible complications, other techniques are being developed. Reports
      evaluating the results of the different techniques are not yet available.

PMID- 16594538
TI  - Intraoperative skeletal traction in the dog: a cadaveric study.
AB  - A standard skeletal traction technique was applied to each major segment of the
      appendicular skeleton of ten fresh dog cadavers. Opposition points and anchorage
      points for the application of traction were determined for each skeletal segment.
      Traction was exerted by means of a micrometric traction stand, connected to the
      limb by bands or a stirrup. Traction was applied to the antebrachium and the
      tibia through nylon traction bands anchored to the metacarpus and metatarsus,
      respectively. A traction stirrup applied to the condylar region was used as the
      anchorage point to load the humerus and femur. Once a peak force of 25 kg weight
      was achieved, the load was monitored for half an hour to check for any variation.
      After that, each skeletal segment was osteotomized in the mid-diaphyseal region,
      and evaluated for any angular malalignment due to a mismatch between the axis of
      the bone and the applied loading. Any ensuing angular malalignment was
      successfully corrected by manoeuvres using the traction stand. The technique used
      in this study to perform intraoperative skeletal traction proved to be reliable
      and consistent for each segment of the appendicular skeleton.

PMID- 16594539
TI  - Clinical application of intraoperative skeletal traction in the dog.
AB  - The purpose of this clinical study was to evaluate the technical feasibility of a
      method for pre-operative and intra-operative traction for reduction of fractures
      of the appendicular skeleton. Traction was used in 24 diaphyseal fractures in 21
      dogs. For each dog, the data pertaining to signalment, limb circumference,
      fracture type, interval between fracture and surgery, and the traction modalities
      were recorded. In patients with a latency between trauma and surgery of less than
      three days, the duration of traction required to realign the bone segments was
      shorter than that required for older fractures (P = 0.02). Intraoperative
      malalignments were corrected by manoeuvres performed with the traction stand.
      Once realigned, fracture segments were kept stable for prolonged periods, without
      the need for a surgical assistant. Postoperative radiographs were evaluated for
      fracture reduction and axial alignment. Postoperative alignment was judged
      excellent in 21 fractures and good in three fractures. Fractures were stabilized
      using external skeletal fixation (n = 10), plates (n = 11) or locked nails (n =
      3), depending on the fracture type. The use of the technique was straight-forward
      and easily applied in a surgical setting. However, its use requires careful
      application because of the potential for iatrogenic tissue damage.

PMID- 16594540
TI  - Use of the ComPact UniLock System for ventral stabilization procedures of the
      cervical spine: a retrospective study.
AB  - This study evaluates clinical application of the ComPact UniLock system for
      ventral stabilization of the cervical spine. Patient material included 13
      consecutive cases, 12 dogs and one cat, with cervical spinal instabilities
      secondary to disc-associated wobbler syndrome (six dogs), traumatic, iatrogenic,
      and disc-associated cervical spinal instability of small dogs (four cases),
      cervical spinal fractures (one dog and one cat), and congenital atlantoaxial
      instability (one dog). The 2.0 system was used in smaller patients and the 2.4
      system was applied in large dogs. Implant failure was observed on follow-up
      radiographs in one dog with a healed C2 fracture and screw pullout occurred in
      one dog with caudal cervical spondylomyelopathy, necessitating revision surgery.
      Implants remained stable throughout the follow-up period in the other cases.
      'Good' or 'excellent' clinical outcome was achieved in 12 patients, including the
      dog with revision surgery. One dog had to be euthanatized due to postoperative
      deterioration of neurological status and development of pneumonia. The ComPact
      UniLock system was found to be a suitable implant for treating cervical
      instabilities of different origin in both small and large patients with lesions
      from C1/C2 to C6/C7. Some problems were encountered in the dogs with disc
      associated Wobbler syndrome, such as lack or slow rate of vertebral fusion and
      partial collapse of the distracted intervertebral space on follow-up radiographs.
      A lack of adequate fusion was most likely related to grafting techniques used.

PMID- 16594541
TI  - Outcome and prognostic factors in non-ambulatory Hansen Type I intervertebral
      disc extrusions: 308 cases.
AB  - Thoracolumbar intervertebral disc disease is the most common cause of caudal
      paresis in dogs. Whilst the pathogenesis of the extrusion has been widely
      studied, treatment protocols and prognostic factors relating to outcome remain
      controversial. Recent studies have examined a multitude of factors relating to
      time to regain ambulation after decompressive surgery. Most intervertebral disc
      herniations occur in the thoracolumbar region, causing upper motor neuron signs
      in the rear limbs, which are thought to have a more favourable prognosis compared
      to the lower motor neuron signs created by herniation of an intervertebral disc
      in the caudal lumbar region. Due to the potential disruption of the lumbar
      intumescence, lower motor neuron signs have been reported as having a less
      favourable prognosis. The purpose of this study was to evaluate the
      intervertebral disc space as a prognostic factor relating to ambulatory outcome
      and time to ambulation after decompressive surgery. Hansen Type I intervertebral
      disc extrusions were studied in 308 non-ambulatory dogs. Preoperative and
      postoperative neurological status, corticosteroid use, signalment, intervertebral
      disc space, postoperative physical rehabilitation, previous hemilaminectomy
      surgery, disc fenestration, return to ambulation, and time to ambulation were
      reviewed.

PMID- 16594542
TI  - Trabecular anisotropy and collagen fibre orientation in the mandibular condyle
      following experimental functional appliance treatment using sheep.
AB  - In order to study the modifying effects of functional appliances on the
      mechanical environment of the temporomandibular joint (TMJ), we characterised the
      structure of the mandibular condyle subsequent to an experimental functional
      appliance intervention. Eight, four-month-old, castrated male Merino sheep, were
      randomly allocated to experimental and control groups (n = 4 in each group).
      Forward mandibular displacement was induced with an intraoral appliance. The
      study period was 15 weeks, during which time fluorochromes were administered to
      all of the animals. Midsagittal sections of the TMJ were selected for analysis
      and trabecular anisotropy was estimated using bone histomorphometry. Only the
      experimental group demonstrated that the trabecular bone in the central condylar
      region was less anisotropic when compared to the subchondral region. Also, the
      variation in trabecular anisotropy of the central condylar region was found to be
      smaller in the experimental group. The collagen fibre orientation was analysed
      under polarised light as the proportion of the dark or bright fibres observed in
      regions which existed before, and regions which formed during the experiment, as
      determined by the fluorochrome labels. In the experimental group, more bright
      collagen fibres were found in the most superior region of the mandibular condyle
      when compared with the controls. These results suggested that the experimental
      functional appliances changed the orientation and pattern of the mechanical
      forces acting on the mandibular condyle, and possibly increased the magnitude of
      the lateral functional forces applied to the most superior part of the condyle
      during such treatments.

PMID- 16594543
TI  - Anabolic effects of acellular bone marrow, platelet rich plasma, and serum on
      equine suspensory ligament fibroblasts in vitro.
AB  - The purpose of this study was to investigate the response of suspensory ligament
      fibroblasts (SLF) to in vitro stimulation using acellular bone marrow (ABM),
      platelet rich plasma (in vitro PRP), and serum as potential treatment modalities
      for suspensory desmitis. Blood, bone marrow, and suspensory ligaments were
      collected from five horses. SLF were harvested, grown until confluent, and
      stimulated with various concentrations of ABM, PRP, equine serum, foetal bovine
      serum, and medium (control). The responses to the treatments were assessed using
      a combination of radio-labeling for total protein synthesis and an ELISA for
      quantification of Cartilage Oligomeric Matrix Protein (COMP) production. Addition
      of all of the samples resulted in significant increases in COMP and total protein
      synthesis over controls (P<0.001). ABM caused the greatest increase in both COMP
      and total protein synthesis by the SLF. Equine ABM, PRP, and serum contain
      anabolic factors that promote matrix synthesis by SLF in vitro, with ABM having
      the greatest effect. Application of bone marrow to injured ligaments may enhance
      healing by providing anabolic factors, other than or in addition to mesenchymal
      stem cells, which stimulate matrix production.

PMID- 16594544
TI  - Matrix metalloproteinase and tissue inhibitor of metalloproteinase in serum and
      synovial fluid of osteoarthritic dogs.
AB  - To better understand the mechanisms responsible for the pathological processes of
      osteoarthritis (OA) and to potentially identify a profile of changes that could
      be predictive of early OA, matrix metalloproteinase-1 (MMP-1) and tissue
      inhibitor of matrix metalloproteinase-2 (TIMP-2) in the synovial fluid and serum
      of normal and osteoarthritic dogs were examined. The concentration of MMP-1 in
      the synovial fluid of osteoarthritic dogs (0.62 +/- 0.16), as measured by
      densitometry, was significantly higher than that found in control dogs (0.42 +/-
      0.19) (P = 0.03). The concentration of MMP-1 in the serum of osteoarthritic dogs
      (0.74 +/- 0.16) was significantly less than that found in control dogs (0.87 +/-
      0.08) (P = 0.05). The concentration of TIMP-2 in the synovial fluid of
      osteoarthritic dogs (46.2 +/- 21.9 ng/ml) was significantly less than that of
      control dogs (122.0 +/- 66.5 ng/ml) (P = 0.009). The concentration of TIMP-2 in
      the serum of osteoarthritic dogs (116.2 +/- 43.1 ng/ml) was not significantly
      different than that of control dogs (95.1 +/- 94.4 ng/ml) (P = 0.554). In
      addition, a phospho-tyrosine immunoprecipitation and mass spectrometry were used
      to isolate and identify interferon-alpha in canine synovial fluid.

PMID- 16594545
TI  - Ventral fixation in atlantoaxial instability with axial fracture in a dog.
AB  - This study reports the diagnosis and the surgical management of atlanto-axial
      instability with an oblique axial fracture in a dog. The fracture was diagnosed
      by radiography and Computed Tomography (CT). In the CT views, the appearance of
      the distortion of the atlantoaxial articular surface was interpreted as
      instability. The stabilization was achieved with the cancellous screws. Following
      the surgery, the neurological status improved and the dog no longer had marked
      neurological deficits.

PMID- 16594546
TI  - Arthrodesis of the tarsometatarsal joint, using type II ESF with acrylic
      connecting bars in four dogs.
AB  - Hyperextension injury of the tarsometatarsal joint (TMTJ) is a debilitating
      injury and arthrodesis of this joint is often the only procedure that can result
      in full return to function. Most surgical procedures described for arthrodesis of
      the tarsometatarsal joint necessitate the use of external, splint or cast, to
      protect the implants used from fatigue failure. This report describes the
      successful use of type II external fixator that spans the tarsometatarsal joint
      in four dogs with hyperextension injury of the tarsometatarsal joint. This
      technique enables the patient to bear weight on the limb immediately after
      surgery until bony fusion is achieved, without the need for an additional
      protecting splint.

PMID- 16594547
TI  - Thermographic evaluation of the efficacy of Kampo medicines.
AB  - Kampo medicine has a specific concept known as "Sho", and herbal formulations are
      prescribed according to the "Sho". "Sho" is defined as "the decision of
      prescription judging from the patient's symptoms, systemic conditions and
      physical constitution generally". In the present study, the authors used
      thermography to evaluate the effects of herbal formulations based on "Sho"
      scientifically. In the cases that were suitable for Keishibukuryogan, the so
      called Keishibukuryogan Sho, a significant skin temperature rise was observed in
      the upper half of the body after the intake of Keishibukuryogan. In a case that
      was suitable for Hochuekkito, the so-called Hochuekkito Sho, a marked elevation
      of skin temperature spread through the upper trunk. Thus, when individuals took
      herbal formulations according to the Sho, a marked skin surface temperature rise
      was observed. On the other hand, in a case that was not appropriate for the
      herbal formulation, a skin temperature rise was not observed after intake of this
      formulation. In an experiment that examined the role of the Keishi (Cinnamon
      Bark) contained in Keishibukuryogan, Keishibukuryogan acted on the abdomen
      including the upper part of the body, while the Keishi contained in
      Keishibukuryogan worked particularly on the upper part of the body. It suggested
      that thermography is useful for an objective evaluation of Sho in Kampo
      medicines, and for identification of the action site of the herbal formulation.

PMID- 16594548
TI  - Increased plasma mRNAs of placenta-specific 1 (PLAC1) and glial cells-missing 1
      (GCM1) in mothers with pre-eclampsia.
AB  - In this study we have investigated whether quantitative analysis of placental
      mRNAs in maternal plasma provides a way to monitor placental status. We measured
      plasma concentrations of human chorionic gonadotropin beta-subunit (betahCG) and
      human placental lactogen (hPL) mRNAs as previously reported mRNAs and pregnancy
      associated plasma protein A (PAPP-A), placenta-specific 1 (PLAC1) and glial cells
      missing 1 (GCM1) mRNAs, which have not been measured during the course of normal
      pregnancy. Firstly, peripheral blood was obtained at various times from healthy
      pregnant women to clarify the time course of placental mRNAs. Secondly, blood was
      obtained from women with pre-eclampsia and gestational age-matched controls to
      examine whether placental mRNAs change in pre-eclampsia. Plasma was separated
      from these samples for extraction of RNA, followed by reverse transcription
      polymerse chain reaction analysis. Median concentrations of PLAC1 and GCM1 mRNA
      in plasma of pre-eclamptic subjects respectively were 1625 and 2141 copies/ml,
      significantly higher than 195 and 881 copies/ml, the values for controls (Mann
      Whitney test, p<0.001). No significant difference was seen in hPL, betahCG, or
      PAPP-A mRNA concentration between pre-eclamptic and control groups. Plasma PLAC1
      and GCM1 mRNAs appear promising as noninvasively measurable molecular markers for
      pre-eclampsia.

PMID- 16594549
TI  - A semi-parametric method for describing the age-specific distribution of clinical
      measurements in cross-sectional study.
AB  - Age-specific distribution of clinical measurements in cross-sectional study is
      described in this paper. Since the distribution of measurements usually varies
      with age, a model with an age-dependent structure is needed. We propose here a
      statistical method for describing the age-specific distribution using an
      extension of the power-normal-model. The age-dependent parameters are to be
      estimated through a nonparametric smoothing technique based on the local
      likelihood method. As a consequence, we can compute a smoothed percentile curve
      of measurements with reference to age. Several kinds of clinical measurements are
      analyzed to determine the proposed method.

PMID- 16594550
TI  - Development of a new pulsatile ventricular assist device.
AB  - We developed a small, lightweight, low-cost implantable ventricular assist device
      (VAD) for use in smaller Japanese subjects. The major advantage of this pump is
      the simplicity of its fabrication. Most parts of the pump were shaped from a
      transparent acrylic block by a turning process, and the diaphragm was made from a
      silicon sheet. Since this method of construction did not require any complex
      processes, we could manufacture many pumps of various shapes. We determined the 
      most efficient shape for the Ebacor VAD using the flow visualization technique.
      The pump showed an output above 6 liters/min under a driving pressure of 300/-100
      mmHg. The pump performance of current VADs is superior to that of the Ebacor VAD,
      because these pumps are larger. Since the Ebacor VAD is small in size, it can be
      driven by the driving system of a normal IABP control unit, which many hospitals
      already have in place. During a 30-day continuous driving performance test of
      this pump, no problems like performance decrements or water and air leakage were
      observed.

PMID- 16594551
TI  - Efficacy of neurotropin in chronic fatigue syndrome: a case report.
AB  - Chronic fatigue syndrome (CFS) is a disorder that causes general fatigue and
      chronic widespread pain. A 28-year-old male visited an outpatient department due
      to general fatigue and pain involving the entire body. He did not suffer from
      fibromyalgia, but he was diagnosed with CFS. At the initial visit, he complained
      of lack of concentration, memory decline, frequent urination, insomnia and
      occasional difficulty of emotional control, as well as general fatigue and pain
      involving the entire body. Four tablets of Neurotropin per day alone were
      administered. General fatigue and pain were gradually alleviated one week later.
      His sleep condition, concentration power, and memory also improved two weeks
      later. Medication was discontinued from 11 weeks based on the patient's judgment
      as he felt little general fatigue and pain involving the entire body. Treatment
      was completed 3 months later. The symptoms disappeared and did not recur five
      months after the discontinuation of Neurotropin. He was looking for a job without
      fatigue and pain 8 months later (5 months after the cessation of treatment). The
      functional mechanisms of Neurotropin in CFS are unknown.

PMID- 16594553
TI  - Uncertain start for full prescribing.

PMID- 16594552
TI  - Zygomatic osteotomy for resection of medial temporal cavernous angioma in
      dominant hemisphere after subdural grid electroencephalographic study.
AB  - We report the treatment of a patient suffering from intractable epilepsy caused
      by a large cavernous angioma in the hippocampus of his dominant hemisphere.
      Surgical removal of a lesion and epileptic focus located in the surrounding brain
      tissue significantly improves seizure conditions. However, total removal of a
      large cavernous angioma in the medial temporal structure of dominant hemisphere
      is occasionally difficult because of the depth of the lesion and its contiguity
      with eloquent brain structures. Furthermore, when an intracranial
      electrocorticogram with grid electrodes is adopted, swelling of soft tissue
      caused by the initial operation for the installation of the grid electrodes
      narrows the operative view obtained by conventional frontotemporal craniotomy. We
      added a zygomatic osteotomy to the operative procedure for the present patient,
      and this enabled us to push soft tissue down and away from the operative field to
      provide a wider operative corridor through which total removal of the lesion and
      epileptic focus was accomplished. The patient has had a favorable postoperative
      course without suffering any seizure for 4 years.

PMID- 16594554
TI  - Standards are key to success of prescribing.

PMID- 16594555
TI  - Raising the bar.

PMID- 16594556
TI  - The waiting game.

PMID- 16594557
TI  - Understanding the risks of the spread of the avian flu virus.
AB  - Although no cases of avian flu have been reported in the UK the virus has spread
      outside south-east Asia. Nurses are likely to be asked about the risks of avian
      flu spreading to the UK, what steps should be taken to prevent or manage
      infection, and whether travel to affected countries is advisable.

PMID- 16594558
TI  - Tinnitus.

PMID- 16594559
TI  - How to remove epidural catheters.

PMID- 16594560
TI  - Identifying poor symptom control in Parkinson's disease.
AB  - The range of drugs available to treat people with Parkinson's disease has never
      been greater. However, patients still encounter difficulties in non-specialist
      settings where there is often confusion over drug selection, dosage and the
      timing of dosages. Small adjustments to the type of drug used, dosage and timing
      can have a significant impact on the control of Parkinson's disease and with it
      the quality of life of patients, carers and their families. This article provides
      a brief overview of Parkinson's disease including how to identify poor symptom
      control.

PMID- 16594561
TI  - Erythropoietin.

PMID- 16594563
TI  - A review of the literature on the nurse role in clinical audit.
AB  - Delivering quality in the NHS is not a new concept. However, the recent focus on
      clinical governance has resulted in the need for effective methods of
      systematically reviewing quality. Clinical audit is a tool that has been created
      for this purpose. This literature review assesses the benefits of clinical audit
      and critiques the nurse's role in the process, addressing any barriers to their
      involvement.

PMID- 16594562
TI  - A health toolkit for people with learning disabilities.
AB  - People with learning disabilities are likely to have greater health needs than
      the majority of the population but are less likely to access health services and
      receive treatment. This article reports on a local initiative to develop a
      toolkit that people with learning disabilities can use to help them address their
      health needs through a simple health check and a health action plan.

PMID- 16594564
TI  - Campaigns for continence.

PMID- 16594565
TI  - Nocturnal enuresis: systems for assessment.
AB  - Childhood nocturnal enuresis, or bedwetting, is a common childhood condition that
      causes children and their families stress and embarrassment and which can
      radically affect the lives of these children. Penny Dobson and Anne Weaver
      outline how nurses can inform and support these families, and describe a research
      based approach, the three systems, which provides a useful framework for
      assessing the problem before choosing the most appropriate treatment strategy.
      Specific help that could be offered teenagers is also outlined.

PMID- 16594566
TI  - Fluid intake and bladder and bowel function.
AB  - Rachel Gilbert discusses the importance of adequate fluid intake for bladder and
      bowel health and the nurse's role in assessing and managing fluid balance.

PMID- 16594568
TI  - The professional relationship between nurses and doctors over recent years.

PMID- 16594567
TI  - Sharpen your study skills.

PMID- 16594569
TI  - A physician as a friend or a friend as your physician.

PMID- 16594570
TI  - Bleeding Kentucky: unjust tort laws cause a hemorrhage of physicians to other
      states.
AB  - Access to medical care in Kentucky is increasingly being lost due to the unjust
      tort climate created by the state constitution and Jural Rights Doctrine. The
      primary mechanism underlying this loss of access is migration of physicians to
      other states with more reasonable tort statutes and lower liability premiums.
      Access to care in rural settings is particularly impaired. The dimensions of this
      effect are explored and other harmful effects on access to care in Kentucky are
      presented in this analysis.

PMID- 16594571
TI  - Analysis of unknown primary carcinomas metastatic to the neck: diagnosis,
      treatment, and outcomes.
AB  - Metastatic squamous cell carcinoma presenting in the neck from an unknown primary
      site represetns 2% to 6% of head and neck cancers. Optimal management of these
      cases remains controversial and continues to evolve with experience. We performed
      a retrospective analysis involving patients treated for unknown primary squamous
      cell carcinomas with metastases to cervical lymph nodes who presented to either
      the University of Kentucky or the Veterans Affairs Hospital of Lexington,
      Kentucky, from 1990 to 2000. Thirty-five out of 173 patients met inclusion
      criteria for carcinoma of unknown primary. The following data subsets were
      analyzed: age, gender, smoking and alcohol use, family history, diagnostic
      studies performed, radiation dose, surgical intervention, number and location of
      pathologic nodes, presence or absence of extracapsular extension, time between
      surgery and radiation, disease-specific and overall survival, response to
      treatment, emergence of a primary tumor, and duration of follow-up. Overall and
      disease-specific survivals were analyzed using, the Kaplan-Meier method and the
      log-rank test was used to assess differences in survival curves. The actuarial 5
      year overall and disease-specific survival of all patients in this study was 54%
      and 63%, respectively. At 10 years, the overall survival declined to 37% with a
      disease-specific survival rate of 49%. The 5-year survival rates stratified by
      nodal stage were 80% for N1 patients, 64.7% for N2, 55.6% for N3, and 0% for any
      M disease. These rates declined to 60% for N1, 52.9% for N2, 11.1% for N3, and 0%
      for any M disease at 10 years (p<.0001). The presence of extracapsular spread,
      increased number of positive lymph nodes, and eventual discovery of a primary
      tumor did not significantly decrease survival in this series. The mean follow-up
      period for patients in this study was 54.8 months. We continue to refine our
      diagnostic and treatment strategies in this group of patients in an effort to
      improve long-term survival and reduce patient morbidity.

PMID- 16594572
TI  - Advances in the management of metastatic androgen-independent prostate cancer.
AB  - Over the last century, advances in the management of men with metastatic androgen
      independent prostate cancer (AIPC), the type of prostate cancer that has
      continued to grow after androgen withdrawal or castration, have been slow.
      Patients with metastatic AIPC usually undergo a cascade of palliative radiation
      therapy and chemotherapy with modest impact on their inevitable deterioration and
      death. Currently, there is no therapy capable of achieving a cure for men with
      AIPC. In the past, chemotherapy was only used for symptomatic patients. Recently
      there has been a paradigm shift after two landmark studies demonstrated an
      improvement in survival for men with AIPC treated with docetaxel-based
      chemotherapy. This review focuses on the management principles and systemic
      chemotherapy options against AIPC. A good understanding of the prognosis,
      treatment options and scientific advances is of utmost importance for the
      physician advising men suffering from AIPC. Research to improve survival and
      quality of life for our patients should be strongly supported.

PMID- 16594573
TI  - Biology versus the Bible.

PMID- 16594574
TI  - Editorial: glargine, a new long-acting insulin analog for diabetic cats.

PMID- 16594575
TI  - Perinuclear antineutrophilic cytoplasmic antibody and response to treatment in
      diarrheic dogs with food responsive disease or inflammatory bowel disease.
AB  - The goal of this study was to investigate the correlation between perinuclear
      antineutrophilic cytoplasmic antibody (pANCA) and clinical scores before and
      after treatment in diarrheic dogs with food-responsive disease (FRD) or
      inflammatory bowel disease (IBD). pANCA serology was evaluated prospectively by
      indirect immunofluorescence in 65 dogs with signs of gastrointestinal disease,
      and if positive, pANCA antibody titers were determined. Thirty-nine dogs with FRD
      responded to a novel diet, and 26 dogs with IBD were treated with
      corticosteroids. The severity of clinical signs was scored by means of a canine
      IBD activity index (CIBDAI). At initial examination, a significantly (P = .002)
      higher percentage of dogs were pANCA-positive in the FRD group (62%) compared
      with the IBD group (23%). pANCA titers were significantly higher (P = .003)
      before treatment in the FRD group (median titer 100) compared with the IBD group
      (median titer 1). However, there was no difference in pANCA titers between the
      groups after respective treatments because dogs in the IBD group had a
      significant increase in pANCA titer after treatment. The CIBDAI score decreased
      significantly (P < .001) after treatment in both groups (74% moderate to severe
      in FRD dogs before versus 8% after treatment; 85% moderate to severe in IBD dogs
      before versus 32% after treatment). There was no correlation between pANCA status
      in FRD or IBD dogs before treatment and scores for CIBDAI, endoscopy, or
      histopathology before or after treatment, except for the endoscopic duodenal
      score in dogs with FRD after treatment (P = .03). A positive pANCA test before
      therapy may aid in the diagnosis of FRD.

PMID- 16594576
TI  - Effects of allopurinol treatment on the progression of chronic nephritis in
      Canine leishmaniosis (Leishmania infantum).
AB  - Forty dogs with canine leishmaniosis (CL) participated in this study, which was
      designed to investigate the effect of allopurinol on the progression of the renal
      lesions associated with this disease. The animals were allocated into 5 groups.
      Group A dogs (n = 12) had neither proteinuria nor renal insufficiency, group B
      dogs (n= 10) had asymptomatic proteinuria, and group C dogs (n = 8) were
      proteinuric and azotemic. Two more groups, CA and CB, comprising 5 dogs each,
      served as controls for groups A and B, respectively. Group A, B, and C dogs
      received allopurinol PO (10 mg/kg q12h) for 6 months, whereas group CA and CB
      dogs were placebo-treated. Serum biochemistry profile, urinalysis, urine
      protein/creatinine ratio, and glomerular filtration rate (GFR) measurements were
      carried out at the beginning of the study, the 3rd month, and the 6th month,
      whereas renal biopsies were carried out only at the beginning and the end of the
      trial. Membranoproliferative glomerulonephritis was the most common cause of
      chronic renal failure. Mesangioproliferative and tubulointerstitial nephritis
      were detected even in group A and CA dogs. Allopurinol not only lowered
      proteinuria in group B dogs but also prevented the deterioration of GFR and
      improved the tubulointerstitial, but not the glomerular, lesions in both group A
      and group B dogs. Further, it resolved the azotemia in 5 of the 8 dogs admitted
      with 2nd stage chronic renal failure (group C). Consequently, treatment with
      allopurinol is advisable in CL cases with asymptomatic proteinuria or 1st-2nd
      stage chronic renal failure.

PMID- 16594577
TI  - Use of glargine and lente insulins in cats with diabetes mellitus.
AB  - The goals of this study were to compare the efficacy of once-daily administered
      Glargine insulin to twice-daily administered Lente insulin in cats with diabetes
      mellitus and to describe the use of a high-protein, low-carbohydrate diet
      designed for the management of diabetes mellitus in cats. All cats with naturally
      occurring diabetes mellitus were eligible for inclusion. Baseline testing
      included a physical examination, serum biochemistry, urinalysis and urine
      culture, serum thyroxine concentration, and serum fructosamine concentration. All
      cats were fed the high-protein, low-carbohydrate diet exclusively. Cats were
      randomized to receive either 0.5 U/kg Lente insulin q12h or 0.5 U/kg Glargine
      insulin q24h. Re-evaluations were performed on all cats at weeks 1, 2, 4, 8, and
      12, and included an assessment of clinical signs, physical examination, 16-hour
      blood glucose curve, and serum fructosamine concentrations. Thirteen cats
      completed the study (Lente, n = 7, Glargine, n = 6). There was significant
      improvement in serum fructosamine and glucose concentrations in all cats but
      there was no significant difference between the 2 insulin groups. Four of the 13
      cats were in complete remission by the end of the study period (Lente, n = 3;
      Glargine, n = 1). The results of the study support the use of once-daily insulin
      Glargine or twice-daily Lente insulin in combination with a high-protein, low
      carbohydrate diet for treatment of feline diabetes mellitus.

PMID- 16594578
TI  - Pharmacokinetics and clinical efficacy of cyclosporine treatment of dogs with
      steroid-refractory inflammatory bowel disease.
AB  - The usual treatment of dogs with inflammatory bowel disease (IBD) consists of
      administration of immunosuppressive doses of steroids. However, some dogs are
      refractory to steroid treatment and pose a significant challenge to the
      veterinarian. Because cyclosporine A (cyA) has been shown to be effective in
      steroid-resistant IBD in humans, the purpose of this study was to investigate the
      pharmacokinetics and clinical efficacy of PO cyA treatment in dogs with steroid
      refractory IBD (n = 14). All dogs were treated with cyA 5 mg/kg PO q24h for a
      period of 10 weeks. A clinical activity score was assigned to assess severity of
      clinical signs before and after treatment. The total number of infiltrating
      lymphocytes and T cells in duodenal biopsies were assessed before and after
      treatment in 9 dogs. In addition, serum concentration of cyA was measured in 8
      dogs over a 24-hour period. Pharmacokinetic profiles in dogs with IBD were
      similar to those of healthy dogs. Improvement of clinical signs was observed in
      12 of 14 dogs with IBD. Median clinical activity score after treatment with cyA
      was significantly reduced from a median score of 9 to a median score of 5 (P =
      0.001). T cell numbers in duodenal biopsies were significantly decreased after
      treatment from a median +/- 95% range in the villous region of 28 (19-30)
      cells/10,000 microm2 before versus 7 (0-10)/10,000 microm2 after treatment, P =
      0.01; and from a median +/- 95% range number in the crypt region of 15 (6-23)
      cells/10,000 microm2 before versus 4 (0-9)/10,000 microm2 after treatment, P =
      0.02, implying T cell lysis as a possible mechanism of action. In conclusion,
      based on this small study, cyA appears to be an effective alternative drug in
      dogs with IBD that are refractory to immunosuppressive doses of steroids.

PMID- 16594579
TI  - Antibiotic sensitivity profiles do not reliably distinguish relapsing or
      persisting infections from reinfections in cats with chronic renal failure and
      multiple diagnoses of Escherichia coli urinary tract infection.
AB  - Older cats with chronic renal failure (CRF) commonly develop urinary tract
      infections (UTI). Uropathogenic Escherichia coli (UPEC) is identified as the
      causal agent of UTI in most affected cats. Infections are often complicated, and
      UPEC infections may persist or recur in these cats. Antibiotic sensitivity
      profiles have been used to distinguish relapsing or persisting UTI from
      reinfection by different clones of the same species. However, the accuracy with
      which antibiograms discriminate different urinary E coli clones in cats is
      uncertain. We studied 17 cystocentesis-derived UPEC isolates collected from 5
      cats with stable CRF and multiple diagnoses of UTI. UTIs were classified as
      relapses versus persistent infections or reinfections using antibiograms
      determined by Kirby-Bauer discs and Etests. Subsequently, clonality of UPEC
      isolates was determined by pulsed-field gel electrophoresis (PFGE). A comparison
      of PFGE results with antibiograms indicated that antibiotic resistance patterns
      varied considerably within several individual E coli clones. Both antibiotic
      susceptibility tests differentiated between relapsing or persistent infections
      and reinfections with only 58% overall efficiency. Thus, antibiotic sensitivity
      profiles cannot be relied upon to distinguish between persisting or relapsing
      infections as compared to reinfections in cats with CRF and multiple diagnoses of
      E coli UTI.

PMID- 16594580
TI  - Molecular detection of microbes in nasal tissue of dogs with idiopathic
      lymphoplasmacytic rhinitis.
AB  - Lymphoplasmacytic rhinitis (LPR) is a common histologic finding in dogs with
      chronic nasal disease; however, potential etiologies of this disorder have not
      been examined. We investigated the hypothesis that specific microbes contribute
      to clinical disease in dogs with LPR. Paraffin-embedded nasal biopsies were
      obtained from 19 dogs with LPR, 10 dogs with nasal neoplasia, and 10 dogs with
      nasal aspergillosis. Nucleic acids were extracted from paraffin blocks, and real
      time quantitative polymerase chain reaction (PCR) was employed for detection of
      target genes for bacterial and fungal DNA, canine adenovirus 2 (CAV-2),
      parainfluenza virus 3 (PI-3), Chlamydial Chlamydophila spp., and Bartonella spp.
      Conventional PCR was used for detection of Mycoplasma spp. Statistical analysis
      was performed using the Mann-Whitney U-test for nonparametric data, and
      significance was set at P < 0.05. DNA or RNA for CAV-2, PI-3, Bartonella,
      Mycoplasma, and Chlamydophila was not detected in any nasal biopsy. DNA loads for
      bacterial DNA did not differ among disease groups. Detection of fungal DNA in
      nasal biopsies was highest in dogs with aspergillosis (P < 0.0001); however,
      nasal biopsies of LPR dogs also displayed higher fungal DNA levels than samples
      from dogs with nasal neoplasia (P = 0.016). Detection of high levels of fungal
      DNA in nasal biopsies of dogs with LPR suggests that fungal organisms may be
      causally associated with the inflammation observed, although the possibility of
      entrapment or accumulation of fungi in the nasal cavity due to chronic
      inflammation cannot be excluded. Further investigations are required to elucidate
      the underlying etiopathogenesis of LPR.

PMID- 16594581
TI  - Physiologic VDD versus nonphysiologic VVI pacing in canine 3rd-degree
      atrioventricular block.
AB  - Historically, ventricular demand, nonphysiologic (VVI) pacing has been the most
      commonly used modality to treat 3rd-degree atrioventricular (AV) block. The goal
      of this study was to determine the feasibility of using a commercial, single
      lead, physiologic (VDD) pacemaker in dogs with 3rd-degree AV block. Furthermore,
      we hoped to characterize and identify differences in the radiographic,
      echocardiographic, neurohormonal, and quality of life consequences of physiologic
      versus nonphysiologic pacing. We evaluated 10 dogs during a 12-week crossover
      study. Acutely, rate-matched physiologic pacing reduced pulmonary capillary wedge
      pressure by 19% compared with nonphysiologic pacing. VDD pacing significantly
      reduced left atrial size normalized to body weight, left atrial-to-aortic root
      ratio, and left ventricular end-systolic dimension and increased fractional
      shortening, aortic Doppler velocity, cardiac output, and stroke volume compared
      with VVI pacing. Variable rate VDD pacing resulted in a significantly slower
      heart rate (HR) during echocardiography than fixed-rate (100 bpm) VVI pacing. AV
      synchronous pacing reduced circulating N-terminal proatrial natriuretic peptide
      (ANP), norepinephrine (NOR), and epinephrine (EPI) concentrations compared with
      asynchronous pacing. There were no significant differences in systemic blood
      pressure, thoracic radiographs, or owner-perceived quality of life. The median
      percentage of AV synchronous pacing during the VDD modality was 99.8% (range, 1.2
      to 99.9%). This study confirms the potential to achieve physiologic pacing with a
      commercial, single-lead system in dogs. VDD pacing improved hemodynamics and
      neurohormonal profiles over asynchronous pacing although the long-term clinical
      benefits of these changes remain to be determined.

PMID- 16594582
TI  - Cardioversion of supraventricular tachycardia using lidocaine in five dogs.
AB  - Sustained supraventricular tachycardia (SVT) may lead to life-threatening
      complications such as tachycardia-induced myocardial failure. We report the use
      of intravenous lidocaine in 5 dogs with SVT. Two dogs had evidence of an
      accessory conduction pathway, 2 were suspected of having an accessory pathway,
      and the mechanism of SVT was unknown in the remaining dog, which subsequently
      developed dilated cardiomyopathy 2 years later. In all cases there was rapid
      conversion to normal sinus rhythm, which was then maintained with oral mexilitene
      (4 dogs) or mexilitene combined with propranolol (1 dog).

PMID- 16594583
TI  - Cardiac troponins as indicators of acute myocardial damage in dogs.
AB  - Cardiac troponin I (cTnI) and T (cTnT) have a high sequence homology across phyla
      and are sensitive and specific markers of myocardial damage. The purpose of this
      study was to evaluate the Cardiac Reader, a human point-of-care system for the
      determination of cTnT and myoglobin, and the Abbott Axsym System for the
      determination of cTnI and creatine kinase isoenzyme MB (CK-MB) in healthy dogs
      and in dogs at risk for acute myocardial damage because of gastric dilatation
      volvulus (GDV) and blunt chest trauma (BCT). In healthy dogs (n = 56), cTnI was
      below detection limits (<0.1 microg/L) in 35 of 56 dogs (reference range 0-0.7
      microg/L), and cTnT was not measurable (<0.05 ng/mL) in all but 1 dog. At
      presentation, cTnI, CK-MB, myoglobin, and lactic acid were all significantly
      higher in dogs with GDV (n = 28) and BCT (n = 8) than in control dogs (P < .001),
      but cTnT was significantly higher only in dogs with BCT (P = .033). Increased
      cTnI or cTnT values were found in 26 of 28 (highest values 1.1-369 microg/L) and
      16 of 28 dogs (0.1-1.7 ng/mL) with GDV, and in 6 of 8 (2.3-82.4 microg/L) and 3
      of 8 dogs (0.1-0.29 ng/mL) with BCT, respectively. In dogs suffering from GDV,
      cTnI and cTnT increased further within the first 48 hours (P < .001). Increased
      cardiac troponins suggestive of myocardial damage occurred in 93% of dogs with
      GDV and 75% with BCT. cTnI appeared more sensitive, but cTnT may be a negative
      prognostic indicator in GDV. Both systems tested seemed applicable for the
      measurement of canine cardiac troponins, with the Cardiac Reader particularly
      suitable for use in emergency settings.

PMID- 16594584
TI  - N-terminal atrial natriuretic peptide immunoreactivity in plasma of cats with
      hypertrophic cardiomyopathy.
AB  - Atrial natriuretic peptide (ANP) is an important regulator of fluid homeostasis
      and vascular tone. We sought to compare N-terminal ANP immunoreactivity (ANP-IR)
      in plasma from cats with and without hypertrophic cardiomyopathy (HCM).
      Secondarily, we evaluated relationships between ANP-IR and echocardiographical
      variables in cats with HCM and healthy cats. Venous blood samples were obtained
      from 17 cats with HCM and from 19 healthy cats. Plasma ANP-IR concentration was
      determined by an enzyme-linked immunoassay. Two cats with HCM had clinical
      evidence of congestive heart failure; the remainder had subclinical disease.
      Plasma ANP-IR concentration was higher in cats with HCM (3,808 +/- 1,406 fmol/L,
      mean +/- SD) than in control cats (3,079 +/- 1,233 fmol/L), but this difference
      was not statistically significant (P = .11; 95% confidence interval [CI] = -166
      to 1,622). There was a significant, but modest correlation between plasma ANP-IR
      concentration and left ventricular posterior wall thickness (r = 0.42; P = .01).
      Additionally, plasma ANP-IR concentration was weakly correlated with left atrial
      size (r = 0.35; P = .03). A linear regression model was developed to further
      explore these relationships. Atrial size and wall thickness were included in the
      model; the 2 explanatory variables had an interactive effect on plasma ANP-IR
      concentration (R2 = 0.27; P = .02). There was no appreciable correlation between
      plasma ANP-IR concentration and any other echocardiographical variable. In a
      population that included cats with subclinical disease, those with HCM did not
      have significantly higher plasma ANP-IR concentration than did healthy cats. An
      exploratory multivariable regression analysis suggested a linear relationship
      between ANP-IR concentration and atrial size, wall thickness, and their
      interaction.

PMID- 16594585
TI  - Use of rheolytic thrombectomy in the treatment of feline distal aortic
      thromboembolism.
AB  - The purpose of this prospective clinical trial was to evaluate the safety and
      efficacy of a commercially available rheolytic thrombectomy system in the
      treatment of naturally occurring feline aortic thromboembolic disease. All 6 cats
      enrolled in the investigation were affected at the level of the distal aorta and
      had signs of the disease affecting both pelvic limbs. Cats were anesthetized and
      an arteriotomy was performed on 1 carotid artery to gain access to the arterial
      system. Selective arterial angiography was used to confirm the presence of
      thromboembolic disease. The thrombectomy system was advanced to the level of the
      thrombus using fluoroscopic guidance. Repeat angiography was used intermittently
      to assess progress of thromboembolus dissolution throughout the procedure. The
      use of the rheolytic thrombectomy system resulted in successful thrombus
      dissolution in 5 of 6 cats. Three of 6 cats survived to discharge. Both of these
      results compare favorably with conventional therapies used in the treatment of
      this disease. Feline distal aortic thromboembolism is a frustrating disease that
      warrants a guarded to poor prognosis. Rheolytic thrombectomy may provide
      veterinarians with an alternative therapy in the treatment of thromboembolic
      diseases, including feline distal aortic thromboembolism.

PMID- 16594586
TI  - Pharmacodynamics of carvedilol in conscious, healthy dogs.
AB  - The purpose of the study reported here was to determine the magnitude and
      duration of beta-blocking efficacy, determine an effective dose and dosing
      interval, and document safety and tolerability of carvedilol given orally in
      clinically normal dogs. Pharmacodynamic data were evaluated in conscious,
      unrestrained, healthy hound dogs at baseline and after long-term oral
      administration of carvedilol (1.5 mg/kg of body weight PO q12h for >5 days). At
      baseline, heart rate (HR) and blood pressure (BP) data were collected
      continuously for 24 hours, and complete echocardiography was performed. This
      protocol was repeated after long-term oral carvedilol administration.
      Additionally, isoproterenol was administered to evaluate the magnitude and
      duration of the nonselective beta-blocking efficacy of carvedilol. An
      isoproterenol challenge was performed 0.75, 1.5, 2.25, 4, 6, 12, and 24 hours
      after carvedilol administration, with echocardiography being performed once at 2
      hours. Plasma samples were obtained prior to each challenge time point for
      determination of plasma carvedilol concentration. Time series regression analysis
      indicated no difference between baseline and carvedilol-induced HR or BP trend
      lines in 6 of 8 dogs. In 2 of 8 dogs, HR, after long-term carvedilol
      administration, was reduced. Carvedilol attenuated isoproterenol-induced changes
      in HR by 54-76% through 12 hours and by 30% at 24 hours. The BP changes were
      attenuated by 80-100% through 12 hours. These data suggest that carvedilol (1.5
      mg/kg PO q12h) in healthy, conscious dogs confers nonselective beta blockade for
      12 hours, with minimal effects on resting HR, BP, and echocardiographic
      variables. Additionally, the magnitude of beta blockade correlated strongly to
      peak plasma carvedilol concentration, suggesting that therapeutic drug monitoring
      may be clinically useful.

PMID- 16594587
TI  - Magnetic resonance imaging findings in Finnish Spitz dogs with focal epilepsy.
AB  - Eleven Finnish Spitz dogs with focal seizures and 3 healthy controls were
      evaluated. General clinical and neurological examinations, blood examination,
      urinalysis, cerebrospinal fluid examination, electroencephalography (EEG), and
      magnetic resonance imaging (MRI) of the brain were performed on all dogs. On EEG
      examination, focal epileptic activity was found in 7 of 11 dogs (64%), and
      generalized epileptic activity was observed in 4 of 11 dogs (36%). MRI (performed
      with 1.5 T equipment) detected changes in 1 epileptic dog. Mild contrast
      enhancement after gadolinium injection was identified in this dog's right
      parietal cortex. However, no such changes were observed in repeated magnetic
      resonance images. Special emphasis was given to seizure history to determine any
      correlations between seizure intervals and MRI findings. Our results indicate
      that Finnish Spitz dogs with focal seizures suffer from focal idiopathic epilepsy
      and have nondetectable findings on MRI or pathology. MRI showed poor sensitivity
      in detecting epileptogenic areas in our patients with focal seizures. Reversible
      MRI changes in 1 dog could have been caused by seizures.

PMID- 16594588
TI  - Clinical and topographic magnetic resonance characteristics of suspected brain
      infarction in 40 dogs.
AB  - Medical records of 40 dogs presented for evaluation of acute-onset,
      nonprogressive, intracranial dysfunction by means of magnetic resonance imaging
      (MRI) diagnosis of brain infarction were reviewed. Location of the brain infarcts
      was: 11 of 38, telencephalic; 8 of 38, thalamic/midbrain; 18 of 38, cerebellar;
      and 3 of 38, multifocal. Telencephalic infarcts developed within the territory of
      the middle cerebral (4/11), rostral cerebral (2/11), and striate (5/11) arteries.
      Thalamic/midbrain infarcts developed within the territory of perforating arteries
      of the caudal portion of the thalamus and rostral portion of the brainstem (8/8).
      All cerebellar infarcts (18/38) were within the territory of the rostral
      cerebellar artery or one of its branches. All infarcts appeared nonhemorrhagic,
      with marked contrast enhancement observed in only 3 of 38 dogs, all of which were
      imaged more than 7 days after the onset of signs of neurologic dysfunction.
      Diffusion-weighted imaging (DWI) sequences were available from 6 dogs, all imaged
      within 5 days of the onset of signs of neurologic dysfunction. Suspected infarcts
      were hyperintense on DWI sequences and were hypointense on the apparent diffusion
      coefficient map. Telencephalic infarcts caused abnormal mental status,
      contralateral postural reaction deficit, contralateral nasal hypalgesia,
      contralateral menace deficit, and ipsilateral circling. Thalamic/midbrain
      infarcts caused contralateral or ipsilateral postural reaction deficit,
      contralateral menace deficit, ipsilateral head tilt or turn, nystagmus,
      ventrolateral strabismus, and anisocoria. Cerebellar infarcts caused ipsilateral
      asymmetric cerebellar quality ataxia, head tilt, intermittent opisthotonus,
      nystagmus, and ipsilateral menace deficit with apparent normal vision.

PMID- 16594589
TI  - Development and evaluation of a Sarcocystis neurona-specific IgM capture enzyme
      linked immunosorbent assay.
AB  - Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease of
      horses caused primarily by the protozoal parasite Sarcocystis neurona. Currently
      available antemortem diagnostic testing has low specificity. The hypothesis of
      this study was that serum and cerebrospinal fluid (CSF) of horses experimentally
      challenged with S neurona would have an increased S neurona-specific IgM (Sn-IgM)
      concentration after infection, as determined by an IgM capture enzyme linked
      immunoassay (ELISA). The ELISA was based on the S neurona low molecular weight
      protein SNUCD-1 antigen and the monoclonal antibody 2G5 labeled with horseradish
      peroxidase. The test was evaluated using serum and CSF from 12 horses
      experimentally infected with 1.5 million S neurona sporocysts and 16 horses
      experimentally infected with varying doses (100 to 100,000) of S neurona
      sporocysts, for which results of histopathologic examination of the central
      nervous system were available. For horses challenged with 1.5 million sporocysts,
      there was a significant increase in serum Sn-IgM concentrations compared with
      values before infection at weeks 2-6 after inoculation (P < .0001). For horses
      inoculated with lower doses of S neurona, there were significant increases in
      serum Sn-IgM concentration at various points in time after inoculation, depending
      on the challenge dose (P < .01). In addition, there was a significant increase
      between the CSF Sn-IgM concentrations before and after inoculation (P < .0001).
      These results support further evaluation of the assay as a diagnostic test during
      the acute phase of EPM.

PMID- 16594590
TI  - Utility of polymerase chain reaction for analysis of antigen receptor
      rearrangement in staging and predicting prognosis in dogs with lymphoma.
AB  - In lymphoid neoplasia, molecular assays to confirm clonality rely on the fact
      that lymphoid cells normally contain DNA regions with unique sequences, resulting
      from recombination of the V, D, and J genes. The purpose of this study was to
      determine the utility of polymerase chain reaction (PCR) for antigen receptor
      rearrangements (PARR) for molecular staging and predicting prognosis in canine
      lymphoma. We hypothesized that the PARR assay would offer a sensitive method for
      detecting neoplastic cells in blood, and that the presence of such cells would be
      a negative prognostic finding compared with dogs with no detectable circulating
      tumor cells. Eighty-six patients with histologically or cytologically confirmed
      lymphoma were studied from initial diagnosis until death or euthanasia. All
      patients had PARR assays of a representative tumor-infiltrated lymph node and
      peripheral whole blood. Sixty-two patients had clonal rearrangements detected in
      the lymph node and were able to be staged by PARR. Seventeen patients (27%) had
      no detectable tumor in their blood and 45 (73%) were blood positive. Our findings
      showed that (1) PARR correlated with clinical stage in that the PARR assay was
      more likely to detect tumor cells in blood in stage 5 lymphomas, (2) PARR was
      more sensitive for detecting circulating tumor cells than visual assessment of
      blood or bone marrow because 80% of stage 3 lymphomas were blood-PARR-positive,
      and (3) PCR stage was not prognostic for disease-free interval (DFI) or survival.

PMID- 16594591
TI  - Urine N-telopeptide excretion in dogs with appendicular osteosarcoma.
AB  - Canine appendicular osteosarcoma (OSA) is a commonly diagnosed cancer that is
      capable of inducing pathologic bone remodeling. Investigating surrogate indices
      of bone metabolism may contribute to the diagnostic and therapeutic management of
      bone malignancies in companion animals. This study evaluated the excretion of N
      terminal telopeptide (NTx), a marker of bone resorption that is detected in
      urine. Sixty-three dogs with appendicular OSA were compared with 29 age-matched
      healthy dogs. Dogs with appendicular OSA had significantly higher baseline urine
      NTx excretion than healthy controls (P < .0001). In 17 dogs with OSA treated with
      either amputation or standardized palliative therapies, significant reductions in
      urine NTx excretion were observed, suggesting that excessive bone resorption in
      dogs with OSA may be linked with focal skeletal osteolysis or its consequences.
      To identify any relationship between indicators of pathologic bone turnover,
      baseline urine NTx excretion was correlated with serum bone alkaline phosphatase
      (bALP) or radiographic tumor lengths at diagnosis. No significant correlations
      were identified between baseline urine NTx excretion and either bALP or tumor
      length. The findings from this study suggest that high urinary NTx excretion may
      support the diagnosis of focal skeletal osteolysis in dogs, and reductions in
      urine NTx excretion after treatment may reflect elimination or minimization of
      pathologic bone resorption.

PMID- 16594592
TI  - Effects of chemotherapy on immune responses in dogs with cancer.
AB  - Chemotherapy is assumed to be immunosuppressive; yet to the authors' knowledge,
      the effects of common chemotherapy protocols on adaptive immune responses in dogs
      with cancer have not been fully evaluated. Therefore, a study was conducted to
      evaluate the effects of 2 common chemotherapy protocols on T- and B-cell numbers
      and humoral immune responses to de novo vaccination in dogs with cancer. Twenty
      one dogs with cancer (12 with lymphoma, 9 with osteosarcoma) were enrolled in a
      prospective study to assess effects of doxorubicin versus multi-drug chemotherapy
      on adaptive immunity. Numbers of circulating T and B cells were assessed by flow
      cytometry, and antibody responses to de novo vaccination were assessed before,
      during, and after chemotherapy. The T- and B-cell numbers before treatment also
      were compared with those of healthy, age-matched, control dogs. Prior to
      treatment, dogs with cancer had significantly fewer (P < .05) CD4+ T cells and
      CD8+ T cells than did healthy dogs. Doxorubicin treatment did not cause a
      significant decrease in T- or B-cell numbers, whereas treatment with combination
      chemotherapy caused a significant and persistent decrease in B-cell numbers.
      Antibody titers after vaccination were not significantly different between
      control and chemotherapy-treated dogs. These findings suggest that chemotherapy
      may have less impact on T-cell numbers and ability to mount antibody responses in
      dogs with cancer than was previously anticipated, though dogs with lymphoma or
      osteosarcoma appear to be relatively T-cell deficient before initiation of
      chemotherapy.

PMID- 16594593
TI  - Relationship between retinoic acid receptor alpha gene expression and growth
      inhibitory effect of all-trans retinoic acid on canine tumor cells.
AB  - Retinoids show antitumor effects on human acute promyelocytic leukemia and other
      tumors via retinoid receptors. In dogs, the role of retinoid receptors in
      inhibiting tumor development remains unclear. To evaluate the correlation between
      the degree of expression of retinoic acid receptor alpha (RARalpha) mRNA and the
      antiproliferative effects of all-trans retinoic acid (ATRA) treatments,
      expression analysis of RARalpha mRNA and cell growth inhibition assay were
      performed on 17 established canine tumor cell lines, including 6 mammary gland
      tumor (MGT) cell lines, 3 osteosarcoma cell lines, 5 melanoma cell lines, and 3
      mast cell tumor (MCT) cell lines. Among the cell lines investigated, all 3 MCT
      cell lines showed high expression of RARalpha, and the most effective cell growth
      inhibition was observed in ATRA-treated MCT cell lines. However, remarkable
      antiproliferative effects of ATRA treatments were not observed on other tumor
      cell lines with moderate or low RARalpha mRNA expression. As a result of the
      relationship between RARalpha mRNA expression and ATRA treatment with regression
      analysis, statistically significant correlation was suggested. Furthermore, real
      time quantitative polymerase chain reaction analysis of RARalpha was performed on
      MCT tissue samples of dogs with spontaneous disease, and 5 of 9 tissues showed
      high expression. These results suggest that ATRA may be an effective antitumor
      agent for MCT in dogs, and that prior measurement of expression of RARalpha mRNA
      may be a good indicator of the effectiveness of ATRA treatment.

PMID- 16594594
TI  - A combination chemotherapy protocol with dose intensification and autologous bone
      marrow transplant (VELCAP-HDC) for canine lymphoma.
AB  - Twenty-eight dogs with lymphoma were treated with a 12-week, 5-drug chemotherapy
      protocol concluding with high-dose cyclophosphamide supported by autologous bone
      marrow transplants. A dose escalation design was used to determine the maximum
      tolerated cyclophosphamide dose (MTD) in this setting. Three cyclophosphamide
      dose levels were given: 300 mg/ m2 IV (groupl, 3 dogs), 400 mg/m2 IV (group 2, 12
      dogs), and 500 mg/m2 IV (group 3, 13 dogs); and the MTD was 500 mg/m2 IV.
      Toxicity was common but mild, and the dose-limiting toxicity was
      myelosuppression, specifically neutropenia. No dog died as a result of treatment
      related toxicity. One dog in group 3 developed fever, neutropenia, and presumed
      sepsis and responded promptly to routine management. No other dog required
      hospitalization. Lower stage and higher cyclophosphamide dose (both increasing
      dose [study groups 1-3], and the highest dose [group 3]) compared with the lower
      doses combined (groups 1 and 2) were significantly associated with longer
      remission duration (all P < .0001). Median remission duration for dogs in group 3
      was 54 weeks, compared with 21 weeks for dogs in groups 1 and 2 combined. Factors
      associated with longer survival time were lower stage (P = .042) and higher
      cyclophosphamide dose (both increasing dose [study groups 1-3], and the highest
      dose [group 3] compared with the lower doses combined [groups 1 and 2]) (P =
      .027). Median survival time for dogs in group 3 was 139 weeks, compared with 43
      weeks and 68 weeks for dogs in groups 1 and 2, respectively.

PMID- 16594595
TI  - Evaluation of platelet aggregation using a point-of-care instrument in retired
      racing Greyhounds.
AB  - Veterinarians involved in Greyhound rescue have anecdotally observed that 10-15%
      of Greyhounds bleed profusely after simple surgical procedures. In most patients,
      platelet counts and hemostasis profiles are normal; therefore, it is possible
      that these dogs have platelet dysfunction. The PFA-100 is a novel point-of-care
      platelet function analyzer that has recently been evaluated as a rapid method to
      assess platelet function in dogs. The objectives of this study were to
      characterize platelet function in a group of healthy Greyhounds by means of the
      PFA-100. Blood samples were collected from the jugular vein from 30 healthy
      Greyhounds. CBC, biochemical profile, PFA-100 assay with collagen/epinephrine
      (COL-EPI) and collagen/ adenosindiphosphate (COL-ADP), plasma von Willebrand
      factor antigen concentration (vWF:Ag), and vWF collagen-binding assay (vWF:CBA)
      were performed. PFA-100 closure times (CTs) with COL/ADP ranged from 63 to 92
      seconds (mean +/- SD, 74.7 +/- 7.9 seconds) and with COL/EPI from 87 to 238
      seconds (138 +/- 41 seconds); vWF: Ag ranged from 22 to 120% (87.52 +/- 25.5%)
      and vWF: CBA ranged from 36 to 102% (77.4 +/- 17.3%); and platelet counts ranged
      from 147 to 265 x 10(9)/L (194.6 +/- 31.64 x 10(9)/L). Greyhound CTs were
      significantly shorter than CTs in a mixed population of 50 healthy non-Greyhound
      dogs, in which the COL/ADP CTs ranged from 61 to 172 seconds (mean +/- SD, 87 +/-
      21.6 seconds), and the COL/ EPI CTs ranged from 81 to 300 seconds (mean +/- SD,
      183 +/- 67.6 seconds; P = 0.005 for COL/ADP CT; P = 0.001 for COL/ EPI CT). Also,
      platelet counts were significantly lower (P = 0.001) and packed cell volume was
      significantly higher (P = 0.001) in the Greyhound than in the non-Greyhound
      group. The PFA-100 is a reproducible method that can be used in the clinical
      setting to assess platelet function in Greyhounds; however, normal CTs in healthy
      Greyhounds are shorter than in other breeds. The results obtained in this study
      will be used to screen for abnormal platelet function in Greyhounds with
      postoperative bleeding.

PMID- 16594596
TI  - Measurement of free thyroxine concentration in horses by equilibrium dialysis.
AB  - The purpose of the study reported here was to validate measurement of free
      thyroxine (fT4) concentration in equine serum by equilibrium dialysis (fT4D), and
      to compare values with fT4 concentration measured directly and with total T4
      (TT4) concentration. The fT4D, fT4, and TT4 concentrations were measured over a
      range of values in euthyroid horses and horses made hypothyroid by administration
      of propylthiouracil (PTU). Concentrations of fT4D (<1.8-83 pmol/L) were
      consistently higher than those of fT4 (<1-40 pmol/L). There was a significant (P
      < .001) regression of fT4D on fT4 in 503 samples from normal horses (y = 2.086x -
      0.430). In baseline samples from 71 healthy euthyroid horses, fT4 concentration
      ranged from 6-21 pmol/L (median, 11 pmol/L; 95% confidence interval [CI]10.5-11.8
      pmol/L), and fT4D concentration ranged from 7-47 pmol/L (median, 22 pmol/L; 95%
      CI 20.9-25.1 pmol/L). Free T4D, fT4, and TT4 concentrations were also measured in
      34 ill horses. Horses consuming PTU and ill horses had significantly (P < .05)
      lower serum concentration of TT4, fT4, and fT4D than did clinically normal,
      healthy horses. If serum samples from ill horses were further subdivided into
      samples from horses that lived and samples from horses that died, fT4D
      concentration was not significantly different in ill horses that lived, compared
      with that in healthy horses, whereas fT4 concentration was still significantly
      decreased in ill horses that died (P < 0.001). We conclude that measurement of
      fT4 concentration by equilibrium dialysis is a valid technique in the horse, and
      its use may provide improved ability to distinguish nonthyroidal illness syndrome
      from hypothyroidism in that species.

PMID- 16594597
TI  - Comparison of four staining methods for detection of mast cells in equine
      bronchoalveolar lavage fluid.
AB  - Mast cells normally are present in equine bronchoalveolar lavage fluid (BALF),
      but usually represent <2% of all cells in healthy horses. An increased percentage
      of mast cells has been associated with airway hyperactivity and inflammatory
      airway diseases, but marked differences are reported between studies in normal
      and diseased horses. Because an abnormal mast cell count may be of clinical
      relevance, we compared the ability of a fast Romanowsky method to stain mast cell
      granules with that of 3 metachromatic stains: automated Romanowsky, May-Grunwald
      Giemsa, and toluidine blue stains. The BALF cells from 24 horses were studied. A
      differential cell count was performed blindly on 400 cells. The percentages of
      mast cells obtained were analyzed by means of repeated-measures analysis of
      variance and Fischer's PLSD test. The Bland and Altman method was used to assess
      agreement among stains. The mean percentage of mast cells in BALF was
      significantly lower with the fast Romanowsky than with the automated Romanowsky,
      May-Grunwald Giemsa, and toluidine blue stains. With the fast Romanowsky stain,
      the metachromatic granules of mast cells were not stained, and their
      identification was based on morphologic criteria. Toluidine blue staining allowed
      detection of the highest mean percentage of mast cells, but was inadequate for
      performing a differential cell count on other cell types. In conclusion, fast
      Romanosky stain may be inadequate for detection of mast cells in equine BALF,
      whereas automated Romanowsky, May-Grunwald Giemsa, and toluidine blue stains
      provide metachromatic staining of mast cell granules.

PMID- 16594598
TI  - Usefulness of a commercial equine IgG test and serum protein concentration as
      indicators of failure of transfer of passive immunity in hospitalized foals.
AB  - Detection of failure of transfer of passive immunity (FTPI) is important in
      reducing morbidity and mortality in neonatal foals. We investigated the
      performance of a commercial equine IgG test (SNAP Foal IgG Test Kit) to diagnose
      FTPI in hospitalized foals. Furthermore, we evaluated the usefulness of serum
      total protein (STP) and serum globulin (SG) concentrations as indicators of FTPI.
      Serum IgG concentration was measured by means of the SNAP test and single radial
      immunodiffusion, and SG and STP concentrations were determined by means of a
      clinical chemistry analyzer. Subjects were 67 hospitalized foals <19 days old.
      The SNAP test was repeated on 37 samples from 29 foals, with identical results
      for 24 samples (kappa statistic, 0.64; 95% confidence interval [CI], 0.46-0.82).
      The sensitivity of the SNAP test to detect serum IgG concentration [IgG] < or
      =400 and < or =800 mg/dl was 90% (95% CI, 71-98%) and 95% (85-99%), respectively,
      and the specificity was 79% (71-82%) and 52% (39-57%), respectively. Sensitivity
      for detection of [IgG] < or =400 mg/dl was not affected (P > .05) by plasma
      fibrinogen concentration, sepsis score, or bacteremia. Specificity for detection
      of [IgG] < or = 800 mg/dl was lower (P < .05) in foals with sepsis score < or =11
      (50% [31-60%] versus 100% [8-100%]) and bacteremia (25% [5-56%] versus 62% [45
      62%]). Sensitivity and specificity of [STP] < or = 5.0 g/dl for [IgG] < or =800
      mg/dl was 94% (83-99%) and 47% (30-56%), respectively. Performance of the SNAP
      test in hospitalized foals is impaired because of low specificity, but can have
      usefulness provided that the properties of the test and characteristics of the
      foal being examined are considered when interpreting the results. The STP and SG
      concentrations are poor sole indicators of FTPI in hospitalized foals, but may be
      useful adjunctive tests.

PMID- 16594599
TI  - Sucrose concentration in blood: a new method for assessment of gastric
      permeability in horses with gastric ulceration.
AB  - A urine sucrose test has recently been reported to be a reliable method of
      detecting gastric ulcers in horses; however, technical difficulties associated
      with urine collection have limited the practical value of the test. The objective
      of this pilot study was to determine whether gastric sucrose permeability, as
      evaluated by serum sucrose concentration, could be used to detect gastric mucosal
      injury in horses. Twelve adult horses with naturally acquired gastric ulceration
      were studied. After a 20-hour nonfeeding period, each horse was dosed with 250 g
      of sucrose via nasogastric intubation. Blood samples were collected at 0, 15, 30,
      45, 60, and 90 minutes, and horses underwent gastroscopy 4 hours later. The
      severity of gastric ulceration in each horse was defined by means of a 4-point
      ulcer-scoring system, and the relationship with serum sucrose concentration was
      analyzed by means of a linear mixed-effects model. Serum sucrose concentration
      was measured by liquid chromatography operating in tandem with electrospray mass
      spectrometry. After nasogastric administration of table sugar, horses with
      moderate to severe gastric ulceration had significant increase in serum sucrose
      concentration at 30, 45, 60, and 90 minutes, relative to earlier times (P < .05).
      Peak sucrose concentration was observed at 45 minutes, and was correlated with
      ulcer severity (Spearman's rank correlation coefficient = 0.898, P < .05). These
      data indicate that determination of sucrose concentration in equine serum may be
      a useful test for identifying horses with endoscopically visible gastric
      ulceration and has potential use as a noninvasive method for screening and
      monitoring horses engaged in racing training and other performance-related
      disciplines.

PMID- 16594600
TI  - Malassezia species isolated from the intermammary and preputial fossa areas of
      horses.
AB  - BACKGROUND: Malassezia-type yeasts previously have been observed on cytologic
      examination of the intermammary region of mares that presented with tail-head
      pruritus; topical antiyeast treatment resolved the pruritus. Further, Malassezia
      dermatitis has been observed in horses in intertriginous areas such as the udder
      and prepuce; the species of yeast was not confirmed. It is not known whether
      healthy mares or male horses can be carriers of this yeast in these body areas.
      HYPOTHESIS: Malassezia spp. are present in the intermammary region in healthy
      mares and the preputial fossa in healthy geldings. ANIMALS: Eleven healthy horses
      (5 mares and 6 geldings). METHODS: Samples of surface material were taken
      digitally from the intermammary area of 5 mares and the preputial fossa region of
      6 geldings. The samples were examined cytologically and were cultured on modified
      Sabouraud's dextrose agar. The DNA from yeast colonies grown on the agar was
      extracted, and samples were assayed using fungal generic polymerase chain
      reaction (PCR) analysis. Amplicons with positive PCR results were sequenced and
      compared with sequences in the BLAST database search program. RESULTS: Of 44
      attempts at culture, 5 yielded a species identified as Malassezia equi, and 2
      yielded M slooffiae. In contrast, of 44 cytologic examinations, yeasts with the
      morphology of Malassezia spp. were seen in 40 samples. CONCLUSIONS AND CLINICAL
      IMPORTANCE: Due to its presence in healthy horses, finding of Malassezia-type
      yeast on cytologic examination may not incriminate it as a pathogen. Despite
      difficulty in culturing, cytologic examination was an effective tool to rapidly
      demonstrate the organism.

PMID- 16594601
TI  - Effect of beclomethasone dipropionate and dexamethasone isonicotinate on lung
      function, bronchoalveolar lavage fluid cytology, and transcription factor
      expression in airways of horses with recurrent airway obstruction.
AB  - Glucocorticoid (GC) therapy is recognized to be effective for the treatment of
      recurrent airway obstruction (RAO) in horses. Anti-inflammatory properties of GC
      are thought to be mediated by suppression of inflammatory gene expression via
      inhibition of transcription factors such as nuclear factor-kappaB (NF-kappaB) and
      activator protein-1 (AP-1). The purpose of this study was to evaluate the effect
      of low-dose inhaled beclomethasone dipropionate and injectable dexamethasone 21
      isonicotinate on clinical signs, pulmonary function, airway cytology, and
      activity of NF-kappaB and AP-1 in bronchial cells of RAO-affected horses. Seven
      horses with RAO were exposed to moldy hay until they developed airway obstruction
      on 3 separate occasions. In a crossover design, they were then treated with a
      placebo (injection on day 1), inhaled beclomethasone (500 microg q12h for 10
      days), or dexamethasone (0.06 mg/kg, IM on day 1) and monitored for 10 days.
      Pulmonary function, bronchoalveolar lavage fluid cytology, and NF-kappaB and AP-1
      activity in bronchial brushing cells were measured before (day 1) and after
      treatment (day 10). Treatment with beclomethasone resulted in significantly
      improved pulmonary function of RAO-affected horses compared with placebo and
      dexamethasone treatments. However, none of the treatments had an effect on
      bronchoalveolar lavage fluid cytology or NF-kappaB and AP-1 activity. These
      findings reveal that, in a model of severe RAO, the benefits of low-dose inhaled
      beclomethasone on pulmonary function are not accompanied by a decrease in airway
      inflammatory cells or a suppression of transcription factors NF-kappaB and AP-1
      DNA-binding activity.

PMID- 16594602
TI  - Risk of after-hours visits to an in-hospital food animal service by species.
AB  - Computer records were accessed documenting in-hospital accessions to the food
      animal service maintained by the University of Missouri, College of Veterinary
      Medicine between January 1, 2001 and December 6, 2004. For each species category,
      the prevalence and relative risk (RR) of after-hours admission were calculated.
      The prevalence of after-hours visits varied from 0.040 for swine to 0.234 for
      South American camelidae. Using cattle as a reference level, the relative risk
      for an after-hours admission was decreased in swine (RR = 0.51) and increased in
      South American camelidae (RR = 3.04) and sheep or goats (RR = 1.66). The
      likelihood of an after-hours admission differed significantly among groups.

PMID- 16594603
TI  - Detection of Neospora caninum tachyzoites in canine cerebrospinal fluid.

PMID- 16594604
TI  - Digoxin and mexiletine sensitivity in a Collie with the MDR1 mutation.

PMID- 16594605
TI  - Hyperphosphatasemia in Scottish terriers: 7 cases.
AB  - Increased serum alkaline phosphatase (ALKP) activity in dogs is commonly
      encountered. In the study reported here, 7 Scottish Terriers were identified with
      hyperphosphatasemia, for which a cause could not be determined. The
      clinicopathologic findings of the syndrome are described and correlated with
      hepatic pathologic changes in biopsy specimens and in specimens obtained at
      postmortem examination. Five of the 7 dogs were related. The ALKP activity ranged
      from 1.7 to 17 times the reference value at the time of biopsy. Increased ALKP
      activity was present for >6 months in 2 dogs and >12 months in 5 dogs; activity
      was > 1,000 U/L for at least 1 measurement in 5 dogs. Results of liver function
      testing, adrenocortical function testing, and hepatic ultrasonography were
      reviewed. Results of histological examination were normal in 6 dogs. One dog had
      regional, chronic cholangitis without evidence of cholestasis. The lesion was
      judged unlikely to account for the degree of hyperphosphatasemia. This study
      provides evidence of possible benign hyperphosphatasemia in Scottish Terriers or
      of another familial disorder causing asymptomatical hyperphosphatasemia without
      corresponding histopathological abnormalities in the liver. Prospective studies
      of ALKP isoenzyme characterization, investigation of skeletal integrity,
      evaluation of additional related dogs to determine prevalence, and longer follow
      up evaluation are necessary to better characterize this finding.

PMID- 16594606
TI  - ACVIM small animal consensus statement on Lyme disease in dogs: diagnosis,
      treatment, and prevention.
AB  - The purpose of this report is to offer a consensus opinion of ACVIM diplomates on
      the diagnosis, treatment, and prevention of Borrelia burgdorferi infections in
      dogs (canine Lyme disease). Clinical syndromes known to commonly be associated
      with canine Lyme disease include polyarthritis and glomerulopathy. Serological
      test results can be used to document exposure to B. burgdorferi but not prove
      illness. Although serum enzyme-linked immunosorbent assay/indirect fluorescent
      antibody assay titers can stay positive for months to years after treatment,
      quantitative C6 peptide antibody paired tests need more study. Serological
      screening of healthy dogs is controversial because it can lead to overdiagnosis
      or overtreatment of normal dogs, most of which never develop Lyme disease.
      However, serological screening can provide seroprevalence and sentinel data and
      stimulate owner education about tick infections and control. Although it is
      unknown whether treatment of seropositive healthy dogs is beneficial, the
      consensus is that seropositive dogs should be evaluated for proteinuria and other
      coinfections and tick control prescribed. Tick control can include a product that
      repels or protects against tick attachment, thereby helping to prevent
      transmission of coinfections as well as Borrelia spp. Seropositive dogs with
      clinical abnormalities thought to arise from Lyme disease generally are treated
      with doxycycline (10 mg/kg q24h for 1 month). Proteinuric dogs might need longer
      treatment as well as medications and diets for protein-losing nephropathy. The
      ACVIM diplomates believe the use of Lyme vaccines still is controversial and most
      do not administer them. It is the consensus opinion that additional research is
      needed to study predictors of illness, "Lyme nephropathy," and coinfections in
      Lyme endemic areas.

PMID- 16594607
TI  - Anthelmintic resistance of gastrointestinal parasites in small ruminants.

PMID- 16594608
TI  - Why RNA and DNA have different structures.
AB  - In the early years of molecular biology--over 50 years ago--we were faced with
      many unknowns. A significant one at the time was the relationship between DNA and
      RNA, both in terms of structure and function. Function is often a reflection of
      structure. Here I outline some of the early research in this area, especially for
      RNA structure, which was completely unknown when we started.

PMID- 16594609
TI  - Regulatory RNAs as mediators of virulence gene expression in bacteria.
AB  - Bacteria exploit functional diversity of RNAs in a wide range of regulatory
      mechanisms to control gene expression. In last few years, small RNA molecules
      have been discovered at a staggering rate in bacteria, mainly in Escherichia
      coli. While functions of many of these RNA molecules are still not known, several
      of them behave as key effectors of adaptive responses, such as environmental cue
      recognition, stress response, and virulence control. Most fascinating, perhaps,
      is the discovery that mRNAs behave as direct sensors of small molecules or of
      environmental cues. The astonishing diversity of RNA-dependent regulatory
      mechanisms is linked to the dynamic properties and versatility of the RNA
      structure. In this review, we relate several recent studies in different
      bacterial pathogens that illustrate the diverse roles of RNA to control virulence
      gene expression.

PMID- 16594610
TI  - Regulatory RNAs in mammals.
AB  - Recent years have brought a dramatic change in our understanding of the role of
      ribonucleic acids (RNAs) within the cell. In addition to the already well-known
      classes of RNAs that take part in the transmission of genetic information from
      DNA to proteins, a new highly heterogeneous group of RNA molecules has emerged.
      The regulatory nonprotein-coding RNAs (npcRNAs) have been shown to be involved in
      modulation of gene expression on both the transcriptional and post
      transcriptional level. They participate in mechanisms of chromatin modification,
      regulation of transcription factor activity, and influencing mRNA stability,
      processing, and translation. npcRNAs are key factors in genetic imprinting,
      dosage compensation of X-chromosome-linked genes, and many processes of
      differentiation and development.

PMID- 16594611
TI  - Aminoglycoside interactions with RNAs and nucleases.
AB  - One of the major challenges in medicine today is the development of new
      antibiotics as well as effective antiviral agents. The well-known aminoglycosides
      interact and interfere with the function of several noncoding RNAs, among which
      ribosomal RNAs (rRNAs) are the best studied. Aminoglycosides are also known to
      interact with proteins such as ribonucleases. Here we review our current
      understanding of the interaction between aminoglycosides and RNA. Moreover, we
      discuss briefly mechanisms behind the inactivation of aminoglycosides, a major
      concern due to the increasing appearance of multiresistant bacterial strains.
      Taken together, the general knowledge about aminoglycoside and RNA interaction is
      of utmost importance in the process of identifying/developing the next generation
      or new classes of antibiotics. In this perspective, previously unrecognized as
      well as known noncoding RNAs, apart from rRNA, are promising targets to explore.

PMID- 16594612
TI  - High-throughput RNA interference in functional genomics.
AB  - RNA interference (RNAi) refers to post-transcriptional silencing of gene
      expression as a result of the introduction of double-stranded RNA into cells. The
      application of RNAi in experimental systems has significantly accelerated
      elucidation of gene functions. In order to facilitate large-scale functional
      genomics studies using RNAi, several high-throughput approaches have been
      developed based on microarray or microwell assays. The recent establishment of
      large libraries of RNAi reagents combined with a variety of detection assays has
      further improved the performance of functional genome-wide screens in mammalian
      cells.

PMID- 16594613
TI  - Antiviral applications of RNAi.
AB  - RNA interference is a natural mechanism by which small interfering (si)RNA
      operates to specifically and potently down-regulate the expression of a target
      gene. This down-regulation has been thought to predominantly function at the
      level of the messenger (m)RNA, post-transcriptional gene silencing (PTGS).
      Recently, the discovery that siRNAs can function to suppress a gene's expression
      at the level of transcription, i.e., transcriptional gene silencing (TGS), has
      created a major paradigm shift in mammalian RNAi. These recent findings
      significantly broaden the role RNA, specifically siRNAs and potentially
      microRNAs, plays in the regulation of gene expression as well as the breadth of
      potential siRNA target sites. Indeed, the specificity and simplicity of design
      makes the use of siRNAs to target and suppress virtually any gene or gene
      promoter of interest a realized technology. Furthermore, since siRNAs are a small
      nucleic acid reagent, they are unlikely to elicit an immune response, making them
      a theoretically good future therapeutic. This review will focus on the
      development, delivery, and potential therapeutic use of antiviral siRNAs in
      treating viral infections as well as emerging viral threats.

PMID- 16594614
TI  - RNA interference: its use as antiviral therapy.
AB  - RNA interference (RNAi) is a sequence-specific gene-silencing mechanism that has
      been proposed to function as a defence mechanism of eukaryotic cells against
      viruses and transposons. RNAi was first observed in plants in the form of a
      mysterious immune response to viral pathogens. But RNAi is more than just a
      response to exogenous genetic material. Small RNAs termed microRNA (miRNA)
      regulate cellular gene expression programs to control diverse steps in cell
      development and physiology. The discovery that exogenously delivered short
      interfering RNA (siRNA) can trigger RNAi in mammalian cells has made it into a
      powerful technique for generating genetic knock-outs. It also raises the
      possibility to use RNAi technology as a therapeutic tool against pathogenic
      viruses. Indeed, inhibition of virus replication has been reported for several
      human pathogens including human immunodeficiency virus, the hepatitis B and C
      viruses and influenza virus. We reviewed the field of antiviral RNAi research in
      2003 (Haasnoot et al. 2003), but many new studies have recently been published.
      In this review, we present a complete listing of all antiviral strategies
      published up to and including December 2004. The latest developments in the RNAi
      field and their antiviral application are described.

PMID- 16594615
TI  - Gene silencing of virus replication by RNA interference.
AB  - Small interfering RNAs (siRNAs) are as effective as long double-stranded RNAs
      (dsRNAs) at targeting and silencing genes by RNA interference (RNAi). siRNAs are
      widely used for assessing gene function in cultured mammalian cells or early
      developing vertebrate embryos. They are also promising reagents for developing
      gene-specific therapeutics. The specific inhibition of viral replication is
      particularly well suited to RNAi, as several stages of the viral life cycle and
      many viral and cellular genes can be targeted. The future success of this
      approach will depend on the recent advances in siRNA-based clinical trials.

PMID- 16594617
TI  - Screening and determination of gene function using randomized ribozyme and siRNA
      libraries.
AB  - Rapid progress in the sequencing of the genomes of model organisms, such as the
      mouse, rat, nematode, fly, and Arabidopsis, as well as the human genome, has
      provided abundant sequence information, but functions of long stretches of these
      genomes remain to be determined. RNA-based technologies hold promise as tools
      that allow us to identify the specific functions of portions of these genomes. In
      particular, catalytic RNAs, known also as ribozymes, can be engineered for
      optimization of their activities in the intracellular environment. The
      introduction of a library of active ribozymes into cells, with subsequent
      screening for phenotypic changes, can be used for the rapid identification ofa
      gene function. Ribozyme technology complements another RNA-based tool for the
      determination of gene function, which is based on libraries of small interfering
      RNAs (siRNAs).

PMID- 16594616
TI  - Progress in the development of nucleic acid therapeutics.
AB  - Abnormal gene expression is a hallmark of many diseases. Gene-specific
      downregulation of aberrant genes could be useful therapeutically and potentially
      less toxic than conventional therapies due its specificity. Over the years, many
      strategies have been proposed for silencing gene expression in a gene-specific
      manner. Three major approaches are antisense oligonucleotides (AS-ONs),
      ribozymes/DNAzymes, and RNA interference (RNAi). In this brief review, we will
      discuss the successes and shortcomings of these three gene-silencing methods, and
      the approaches being taken to improve the effectiveness of antisense molecules.
      We will also provide an overview of some of the clinical applications of
      antisense therapy.

PMID- 16594618
TI  - Ribozymes and siRnas: from structure to preclinical applications.
AB  - The discovery that nucleic acids mediated the inhibition of gene expression in a
      sequence-specific manner has provided the scientific community with a potentially
      important tool to analyse gene function and validate drug targets. Selective
      inhibition of gene expression by ribozymes and small interfering RNAs (siRNAs) is
      being explored for potential therapeutics against viral infections, inflammatory
      disorders, haematological diseases and cancer. In order to be used as
      pharmaceutical drugs, chemical modifications are necessary to increase their
      stability in vivo. However, such modifications should not affect either the
      ribozyme cleavage activity or the incorporation of the siRNAs into the RNA
      interference (RNAi) targeting complex and subsequent mRNA cleavage. To attain
      stability, ribozymes and siRNAs must also overcome several other problems,
      including accessibility to target messenger RNAs (mRNAs), efficient delivery to
      target cells and unwanted non-specific effects.

PMID- 16594619
TI  - Strategies to identify potential therapeutic target sites in RNA.
AB  - Antisense agents are powerful tools to inhibit gene expression in a sequence
      specific manner. They are used for functional genomics, as diagnostic tools and
      for therapeutic purposes. Three classes of antisense agents can be distinguished
      by their mode of action: single-stranded antisense oligodeoxynucleotides;
      catalytic active RNA/DNA such as ribozymes, DNA- or locked nucleic acid
      (LNA)zymes; and small interfering RNA molecules known as siRNA. The selection of
      target sites in highly structured RNA molecules is crucial for their successful
      application. This is a difficult task, since RNA is assembled into nucleoprotein
      complexes and forms stable secondary structures in vivo, rendering most of the
      molecule inaccessible to intermolecular base pairing with complementary nucleic
      acids. In this review, we discuss several selection strategies to identify
      potential target sites in RNA molecules. In particular, we focus on combinatorial
      library approaches that allow high throughput screening of sequences for the
      design of antisense agents.

PMID- 16594620
TI  - Oligonucleotide-based antiviral strategies.
AB  - In the age of extensive global traffic systems, the close neighborhood of man and
      livestock in some regions of the world, as well as inadequate prevention measures
      and medical care in poorer countries, greatly facilitates the emergence and
      dissemination of new virus strains. The appearance of avian influenza viruses
      that can infect humans, the spread of the severe acute respiratory syndrome
      (SARS) virus, and the unprecedented raging of human immunodeficiency virus (HIV)
      illustrate the threat of a global virus pandemic. In addition, viruses like
      hepatitis B and C claim more than one million lives every year for want of
      efficient therapy. Thus, new approaches to prevent virus propagation are urgently
      needed. Antisense strategies are considered a very attractive means of inhibiting
      viral replication, as oligonucleotides can be designed to interact with any viral
      RNA, provided its sequence is known. The ensuing targeted destruction of viral
      RNA should interfere with viral replication without entailing negative effects on
      ongoing cellular processes. In this review, we will give some examples of the
      employment of antisense oligonucleotides, ribozymes, and RNA interference
      strategies for antiviral purposes. Currently, in spite of encouraging results in
      preclinical studies, only a few antisense oligonucleotides and ribozymes have
      turned out to be efficient antiviral compounds in clinical trials. The advent of
      RNA interference now seems to be refueling hopes for decisive progress in the
      field of therapeutic employment of antisense strategies.

PMID- 16594621
TI  - Gene-expressed RNA as a therapeutic: issues to consider, using ribozymes and
      small hairpin RNA as specific examples.
AB  - In recent years there has been a greater appreciation of both the role of RNA in
      intracellular gene regulation and the potential to use RNA in therapeutic
      modalities. In the latter case, RNA can be used as a therapeutic target or a
      drug. The chapters in this volume cover the varied and potent actions of RNA as
      antisense, ribozymes, aptamers, microRNA and small hairpin RNA in gene
      regulation, as well as their use as potential therapeutics for metabolic and
      infectious diseases. Our group has been involved in the development of anti-HIV
      gene expression constructs to treat HIV. In this chapter, we address the relevant
      scientific and some of the commercial issues in the use of RNA as a therapeutic.
      Specifically, the chapter discusses delivery, expression, potency, toxicity and
      commercial development using, as examples, hammerhead ribozymes and small hairpin
      RNA.

PMID- 16594622
TI  - RNA aptamers: from basic science towards therapy.
AB  - The SELEX technique (systematic evolution of ligands by exponential enrichment)
      provides a powerful tool for the in vitro selection of nucleic acid ligands
      (aptamers) from combinatorial oligonucleotide libraries against a target
      molecule. In the beginning of the technique's use, RNA molecules were identified
      that bind to proteins that naturally interact with nucleic acids or to small
      organic molecules. In the following years, the use of the SELEX technique was
      extended to isolate oligonucleotide ligands (aptamers) for a wide range of
      proteins of importance for therapy and diagnostics, such as growth factors and
      cell surface antigens. These oligonucleotides bind their targets with similar
      affinities and specificities as antibodies do. The in vitro selection of
      oligonucleotides with enzymatic activity, denominated aptazymes, allows the
      direct transduction of molecular recognition to catalysis. Recently, the use of
      in vitro selection methods to isolate protein inhibitors has been extended to
      complex targets, such as membrane-bound receptors, and even entire cells. RNA
      aptamers have also been expressed in living cells. These aptamers, also called
      intramers, can be used to dissect intracellular signal transduction pathways. The
      utility of RNA aptamers for in vivo experiments, as well as for diagnostic and
      therapeutic purposes, is considerably enhanced by chemical modifications, such as
      substitutions of the 2'-OH groups of the ribose backbone in order to provide
      resistance against enzymatic degradation in biological fluids. In an alternative
      approach, Spiegelmers are identified through in vitro selection of an unmodified
      D-RNA molecule against a mirror-image (i.e. a D-peptide) of a selection target,
      followed by synthesis of the unnatural nuclease-resistant L-configuration of the
      RNA aptamer that recognizes the natural configuration of its selection target
      (i.e. a L-peptide). Recently, nuclease-resistant inhibitory RNA aptamers have
      been developed against a great variety of targets implicated in disease. Some
      results have already been obtained in animal models and in clinical trials.

PMID- 16594623
TI  - RNA aptamers directed against oligosaccharides.
AB  - Nucleic acid molecules are designed to interact predominantly with proteins or
      complementary nucleic acids. Interaction of nucleic acids with carbohydrates,
      abundant constituents of glycoproteins and glycolipids, are not common in cells.
      Biomedical applications of nucleic acids targeted against oligosaccharides, which
      are involved in the function of receptors, immune answer, host interaction with
      invading infectious agents, and cancer metastasis, are feasible. In vitro
      selection of nucleic acids interacting with oligoand polysaccharides is a
      promising strategy to identify potential inhibitors of biochemical recognition
      processes in which carbohydrates are involved. Several RNA and DNA aptamers
      directed against carbohydrates have already been isolated and characterized. The
      results are summarized in this article, and an attempt is made to draw initial
      conclusions concerning the perspectives of the outlined approach.

PMID- 16594624
TI  - Aptamer-based biosensors: biomedical applications.
AB  - This chapter considers the use of aptamer-based biosensors (generally termed
      'aptasensors') in various biomedical applications. A comparison of antibodies and
      aptamers is made with respect to their use in the development of biosensors. A
      brief introduction to biosensor design and theory is provided to illustrate the
      principles of the field. Various transduction approaches, viz. optical,
      fluorescence, acoustic wave and electrochemical, are discussed. Specific
      biomedical applications described include RNA folding, high-throughput screening
      of drugs, use as receptors for measuring biological concentrations, detection of
      platelet-derived growth factor, protein binding and detection of HIV-1 Tat
      protein.

PMID- 16594625
TI  - Application of aptamers in therapeutics and for small-molecule detection.
AB  - Nucleic acids that can bind with high affinity and specificity to target
      molecules are called "apta mers". Aptamers recognise a large variety of different
      molecule classes. The main focus of this chapter is small molecules as targets.
      Aptamers are applied complementarily to antibody technologies and can substitute
      antibodies or small molecules wherever their different properties, such as
      biochemical nature or highly discriminating capacities, are advantageous.
      Examples of promising applications of these versatile molecules are discussed in
      the field of therapeutics and biotechnology with a special view to small-molecule
      detection.

PMID- 16594626
TI  - RNA aptamers as potential pharmaceuticals against infections with African
      trypanosomes.
AB  - Protozoal pathogens cause symptomatic as well as asymptomatic infections. They
      have a worldwide impact, which in part is reflected in the long-standing search
      for antiprotozoal chemotherapy. Unfortunately, effective treatments for the
      different diseases are by and large not available. This is especially true for
      African trypanosomiasis, also known as sleeping sickness. The disease is an
      increasing problem in many parts of sub-Saharan Africa, which is due to the lack
      of new therapeutics and the increasing resistance against traditional drugs such
      as melarsoprol, berenil and isometamidium. Considerable progress has been made
      over the past 10 years in the development of nucleic acid-based drug molecules
      using a variety of different technologies. One approach is a combinatorial
      technology that involves an iterative Darwinian-type in vitro evolution process,
      which has been termed SELEX for "systematic evolution of ligands by exponential
      enrichment". The procedure is a highly efficient method of identifying rare
      ligands from combinatorial nucleic acid libraries of very high complexity. It
      allows the selection of nucleic acid molecules with desired functions, and it has
      been instrumental in the identification of a number of synthetic DNA and RNA
      molecules, so-called aptamers that recognize ligands of different chemical
      origin. Aptamers typically bind their target with high affinity and high
      specificity and have successfully been converted into pharmaceutically active
      compounds. Here we summarize the recent examples of the SELEX technique within
      the context of identifying high-affinity RNA ligands against the surface of the
      protozoan parasite Trypanosoma brucei, which is the causative agent of sleeping
      sickness.

PMID- 16594627
TI  - RNA targeting using peptide nucleic acid.
AB  - The efforts towards peptide nucleic acid (PNA) drug discovery using cellular RNAs
      as molecular targets is briefly reviewed, with special emphasis on recent
      developments. Special attention is given to cellular delivery in vivo
      bioavailability and the possibilities of using PNA oligomers to (re)direct
      alternative splicing of pre-messenger (m)RNA.

PMID- 16594628
TI  - Locked nucleic acid: high-affinity targeting of complementary RNA for RNomics.
AB  - Locked nucleic acid (LNA) is a nucleic acid analog containing one or more LNA
      nucleotide monomers with a bicyclic furanose unit locked in an RNA-mimicking
      sugar conformation. This conformational restriction is translated into
      unprecedented hybridization affinity towards complementary single-stranded RNA
      molecules. That makes fully modified LNAs, LNA/DNA mixmers, or LNA/RNA mixmers
      uniquely suited for mimicking RNA structures and for RNA targeting in vitro or in
      vivo. The focus of this chapter is on LNA antisense, LNA-modified DNAzymes
      (LNAzymes), LNA-modified small interfering (si)RNA (siLNA), LNA-enhanced
      expression profiling by real-time RT-PCR and detection and analysis of microRNAs
      by LNA-modified probes.

PMID- 16594629
TI  - Engineering RNA-based circuits.
AB  - Nucleic acids can modulate gene function by base-pairing, via the molecular
      recognition of proteins and metabolites, and by catalysis. This diversity of
      functions can be combined with the ability to engineer nucleic acids based on
      Watson-Crick base-pairing rules to create a modular set of molecular "tools" for
      biotechnological and medical interventions in cellular metabolism. However, these
      individual RNA-based tools are most powerful when combined into rational logical
      or regulatory circuits, and the circuits can in turn be evolved for optimal
      function. Examples of genetic circuits that control translation and transcription
      are herein detailed, and more complex circuits with medical applications are
      anticipated.

PMID- 16594630
TI  - Selection of RNase-resistant RNAs.
AB  - All RNA types are susceptible to ribonuclease (RNase) digestion, which might be a
      serious problem for several in vitro and in vivo applications. RNase resistance
      can be reached through chemical modifications or the selection of stable
      secondary structures via SELEX (systematic evolution of ligands by exponential
      enrichment). This chapter focuses on the selection of natural RNase-resistant
      RNAs, enriched by a selection process in the presence of RNase T1. Results of
      these investigations led to the identification of a particular structural motif,
      the tetraloop. Further applications could be the advised use of such motifs in
      order to reach higher stability of RNA molecules.

PMID- 16594631
TI  - Simultaneous population optimal design for pharmacokinetic-pharmacodynamic
      experiments.
AB  - Multiple outputs or measurement types are commonly gathered in biological
      experiments. Often, these experiments are expensive (such as clinical drug
      trials) or require careful design to achieve the desired information content.
      Optimal experimental design protocols could help alleviate the cost and increase
      the accuracy of these experiments. In general, optimal design techniques ignore
      between-individual variability, but even work that incorporates it (population
      optimal design) has treated simultaneous multiple output experiments separately
      by computing the optimal design sequentially, first finding the optimal design
      for one output (eg, a pharmacokinetic [PK] measurement) and then determining the
      design for the second output (eg, a pharmacodynamic [PD] measurement).
      Theoretically, this procedure can lead to biased and imprecise results when the
      second model parameters are also included in the first model (as in PK-PD
      models). We present methods and tools for simultaneous population D-optimal
      experimental designs, which simultaneously compute the design of multiple output
      experiments, allowing for correlation between model parameters. We then apply
      these methods to simulated PK-PD experiments. We compare the new simultaneous
      designs to sequential designs that first compute the PK design, fix the PK
      parameters, and then compute the PD design in an experiment. We find that both
      population designs yield similar results in designs for low sample number
      experiments, with simultaneous designs being possibly superior in situations in
      which the number of samples is unevenly distributed between outputs. Simultaneous
      population D-optimality is a potentially useful tool in the emerging field of
      experimental design.

PMID- 16594632
TI  - Equivalence studies for complex active ingredients and dosage forms.
AB  - This article examines the United States Pharmacopeia (USP) and its role in
      assessing the equivalence and inequivalence of biological and biotechnological
      drug substances and products-a role USP has played since its founding in 1820. A
      public monograph in the United States Pharmacopeia-National Formulary helps
      practitioners and other interested parties understand how an article's strength,
      quality, and purity should be controlled. Such a monograph is a standard to which
      all manufactured ingredients and products should conform, and it is a starting
      point for subsequent-entry manufacturers, recognizing that substantial additional
      one-time characterization studies may be needed to document equivalence. Review
      of these studies is the province of the regulatory agency, but compendial tests
      can provide clarity and guidance in the process.

PMID- 16594633
TI  - The role of crystallography in drug design.
AB  - Structure and function are intimately related. Nowhere is this more important
      than the area of bioactive molecules. It has been shown that the
      enantioselectivity of an enzyme is directly related to its chirality. X-ray
      crystallography is the only method for determining the "absolute" configuration
      of a molecule and is the most comprehensive technique available to determine the
      structure of any molecule at atomic resolution. Results from crystallographic
      studies provide unambiguous, accurate, and reliable 3-dimensional structural
      parameters, which are prerequisites for rational drug design and structure-based
      functional studies.

PMID- 16594634
TI  - Ophthalmic drug design based on the metabolic activity of the eye: soft drugs and
      chemical delivery systems.
AB  - Despite its apparent easy accessibility, the eye is, in fact, well protected
      against the absorption of foreign materials, including therapeutic agents, by the
      eyelids, by the tear-flow, and by the permeability barriers imposed by the cornea
      on one side and the blood-retinal barrier on the other. Most existing ophthalmic
      drugs were adapted from other therapeutic applications and were not specifically
      developed for the treatment of eye diseases; hence, they are not well suited to
      provide eye-specific effects without causing systemic side effects. A real
      breakthrough in the area of ophthalmic therapeutics can be achieved only by
      specifically designing new drugs for ophthalmic applications to incorporate the
      possibility of eye targeting into their chemical structure. Possibilities
      provided along these lines by designing chemical delivery systems (CDSs) and soft
      drugs within the framework of retrometabolic drug design are reviewed here. Both
      are general concept applicable in almost any therapeutic area. This review will
      concentrate on beta-adrenergic agonists and anti-inflammatory corticosteroids,
      where clinical results obtained with new chemical entities, such as betaxoxime,
      adaprolol, loteprednol etabonate, and etiprednol dicloacetate, exist to support
      the advantages of such metabolism-focused, ophthalmic-specific drug design
      approaches.

PMID- 16594636
TI  - Role of monoamine transporters in mediating psychostimulant effects.
AB  - Monoamine transporters such as the dopamine (DA) transporter (DAT) and the
      vesicular monoamine transporter-2 (VMAT-2) are critical regulators of DA
      disposition within the brain. Alterations in DA disposition can lead to
      conditions such as drug addiction, Parkinson's disease, and schizophrenia, a fact
      that underscores the importance of understanding DAergic signaling.
      Psychostimulants alter DAergic signaling by influencing both DAT and VMAT-2, and
      although the effects of these drugs result in increased levels of synaptic DA,
      the mechanisms by which this occurs and the effects that these drugs exert on DAT
      and VMAT-2 vary. Many psychostimulants can be classified as releasers (ie,
      amphetamine analogs) or uptake blockers (ie, cocaine-like drugs) based on the
      mechanism of their acute effects on neurotransmitter flux through the DAT.
      Releasers and uptake blockers differentially modulate the activity and
      subcellular distribution of monoamine transporters, a phenomenon likely related
      to the neurotoxic potential of these drugs to DAergic neurons. This article will
      review some of the recent findings whereby releasers and uptake blockers alter
      DAT and VMAT-2 activity and how these alterations may be involved in
      neurotoxicity, thus providing insight on the neurodegeneration observed in
      Parkinson's disease.

PMID- 16594637
TI  - Transport systems for opioid peptides in mammalian tissues.
AB  - Transmembrane transport of endogenous as well as synthetic opioid peptides is a
      critical determinant of pharmacokinetics and biologic efficacy of these peptides.
      This transport process influences the distribution of opioid peptides across the
      blood-brain barrier and their elimination from the body. A multitude of transport
      systems that recognize opioid peptides as substrates have been characterized at
      the functional level, and these transport systems are expressed differentially at
      different sites in the body. Many of these transport systems have been identified
      at the molecular level. These include the H(+)-coupled peptide transporters PEPT1
      and PEPT2, the adenosine triphosphate-dependent efflux transporters P
      glycoprotein and multidrug resistance-related protein 2, and several members of
      the organic anion-transporting polypeptide gene family. There are however many
      additional transport systems that are known to transport opioid peptides but
      their molecular identities still remain unknown.

PMID- 16594638
TI  - Shear-induced variability in the United States Pharmacopeia Apparatus 2:
      modifications to the existing system.
AB  - The hydrodynamics within the United States Pharmacopeia Apparatus 2 have been
      shown to be highly non-uniform with a potential to yield substantial variability
      in dissolution rate measurements. Through the use of readily available
      engineering tools, several geometric modifications to the device were evaluated
      in this study. Specifically, we examined the influence of impeller clearance,
      agitator type (radial and axial), and vessel geometry (PEAK vessel) on the fluid
      flow properties and their relation to measured dissolution rates. Increasing the
      impeller clearance was observed to exacerbate the heterogeneity in shear and
      would likely result in greater variability in dissolution measurements. Altering
      the impeller type was shown to yield changes in the hydrodynamic behavior;
      however, the overall properties and problems with the test remain the same. Use
      of the PEAK vessel was observed to reduce shear heterogeneity in the regions
      where tablets are most likely to visit during testing; however, higher shear
      rates may result in the inability to discriminate between true differences in
      dissolution rates.

PMID- 16594635
TI  - Mechanisms of drug-induced delayed-type hypersensitivity reactions in the skin.
AB  - Cutaneous drug reactions (CDRs) are the most commonly reported adverse drug
      reactions. These reactions can range from mildly discomforting to life
      threatening. CDRs can arise either from immunological or nonimmunological
      mechanisms, though the preponderance of evidence suggests an important role for
      immunological responses. Some cutaneous eruptions appear shortly after drug
      intake, while others are not manifested until 7 to 10 days after initiation of
      therapy and are consistent with delayed-type hypersensitivity. This review
      discusses critical steps in the initiation of delayed-type hypersensitivity
      reactions in the skin, which include protein haptenation, dendritic cell
      activation/migration and T-cell propagation. Recently, an alternative mechanism
      of drug presentation has been postulated that does not require bioactivation of
      the parent drug or antigen processing to elicit a drug-specific T-cell response.
      This review also discusses the role of various immune-mediators, such as
      cytokines, nitric oxide, and reactive oxygen species, in the development of
      delayed-type drug hypersensitivity reactions in skin. As keratinocytes have been
      shown to play a crucial role in the initiation and propagation of cutaneous
      immune responses, we also discuss the means by which these cells may initiate or
      modulate CDRs.

PMID- 16594639
TI  - Viewing chemokines as a third major system of communication in the brain.
AB  - There is irrefutable proof that opioids and other classes of centrally acting
      drugs have profound effects on the immune system. Evidence is mounting that
      products of the immune system, such as chemokines, can reciprocally alter the
      actions of these drugs and the endogenous ligands for their receptors. Chemokines
      are a family of small (8 to 12 kDa) proteins involved in cellular migration and
      intercellular communication. With a few exceptions, they act on more than one
      receptor. Although the chemokines and their G protein-coupled receptors are
      located in both glia and neurons throughout the brain, they are not uniformly
      distributed. They are found in such brain areas as the hypothalamus, nucleus
      accumbens, limbic system, hippocampus, thalamus, cortex, and cerebellum. Among
      the chemokines differentially localized in brain neurons and glia are CCL2/MCP-1,
      CXCL12/SDF-1alpha, CX3CL1/fractalkine, CXCL10/IP 10, CCL3/MIP-1alpha, and
      CCL5/RANTES. Functional roles for the chemokine system, composed of the chemokine
      ligands and their receptors, have been suggested in brain development and
      heterologous desensitization. The system can alter the actions of neuronally
      active pharmacological agents such as opioids and cannabinoids and interact with
      neurotransmitter systems. In this review, we propose that the endogenous
      chemokine system in the brain acts in concert with the neurotransmitter and
      neuropeptide systems to govern brain function. It can thus be thought of as the
      third major system in the brain.

PMID- 16594640
TI  - Hallucinogen actions on 5-HT receptors reveal distinct mechanisms of activation
      and signaling by G protein-coupled receptors.
AB  - We review the effect of some key advances in the characterization of molecular
      mechanisms of signaling by G protein-coupled receptors (GPCRs) on our current
      understanding of mechanisms of drugs of abuse. These advances are illustrated by
      results from our ongoing work on the actions of hallucinogens on serotonin (5-HT)
      receptors. We show how a combined computational and experimental approach can
      reveal specific modes of receptor activation underlying the difference in
      properties of hallucinogens compared with nonhallucinogenic congeners. These
      modes of activation-that can produce distinct ligand-dependent receptor states
      are identified in terms of structural motifs (SM) in molecular models of the
      receptors, which were shown to constitute conserved functional microdomains (FM).
      The role of several SM/FMs in the activation mechanism of the GPCRs is presented
      in detail to illustrate how this mechanism can lead to ligand-dependent modes of
      signaling by the receptors. Novel bioinformatics tools are described that were
      designed to support the quantitative mathematical modeling of ligand-specific
      signaling pathways activated by the 5-HT receptors targeted by hallucinogens. The
      approaches for mathematical modeling of signaling pathways activated by 5-HT
      receptors are described briefly in the context of ongoing work on detailed
      biochemical models of 5-HT2A, and combined 5-HT2A/5-HT1A, receptor-mediated
      activation of the MAPK 1,2 pathway. The continuing need for increasingly more
      realistic representation of signaling in dynamic compartments within the cell,
      endowed with spatio-temporal characteristics obtained from experiment, is
      emphasized. Such developments are essential for attaining a quantitative
      understanding of how the multiple functions of a cell are coordinated and
      regulated, and to evaluate the specifics of the perturbations caused by the drugs
      of abuse that target GPCRs.

PMID- 16594642
TI  - Pharmacokinetic and pharmacodynamic effects of high-dose monoclonal antibody
      therapy in a rat model of immune thrombocytopenia.
AB  - Intravenous administration of pooled, polyvalent human immunoglobulin (IVIG) has
      been used for over 20 years as a therapy for immune thrombocytopenia (ITP). IVIG
      is available in limited quantities, and clinical preparations have been
      associated with the transfer of human pathogens. We have proposed that high-dose
      monoclonal antibody may be used in lieu of IVIG to achieve beneficial effects in
      the treatment of ITP. The current study investigates the effects of high-dose
      monoclonal antibody therapy in a rat model of ITP. Hybridoma cells secreting a
      murine monoclonal antiplatelet antibody (7E3) and murine monoclonal anti
      methotrexate IgG (AMI) were grown in serum-free media. Next, 7E3, 8 mg kg(-1),
      was administered intravenously to rats following pretreatment with saline or AMI
      (1 g kg(-1) IV). AMI and 7E3 plasma concentrations were determined via enzyme
      linked immunosorbent assay, and platelet count was determined with a Cell-Dyne
      hematology analyzer. Severe, transient thrombocytopenia was induced by 7E3.
      Platelet counts dropped to approximately 8% of initial values within 1 hour after
      7E3 administration. AMI pretreatment dramatically affected 7E3-induced
      thrombocytopenia, significantly altering the time course of thrombocytopenia (P <
      .05) and significantly decreasing the severity of 7E3-induced thrombocytopenia
      (ie, following AMI pretreatment, nadir platelet count was greater than 8-fold
      that of the control group, P < .05). In addition, AMI pretreatment induced a 57%
      increase in 7E3 clearance (1.13 +/- 0.13 mL h(-1) kg(-1) vs 0.72 +/- 0.08 mL h(
      1) kg(-1), P < .05). Consequently, high-dose monoclonal antibody therapy
      attenuated thrombocytopenia and produced a moderate increase in the clearance of
      antiplatelet antibodies in a rat model of ITP.

PMID- 16594641
TI  - Neuronal nicotinic acetylcholine receptor expression and function on nonneuronal
      cells.
AB  - Of the thousands of proven carcinogens and toxic agents contained within a
      cigarette, nicotine, while being the addictive agent, is often viewed as the
      least harmful of these compounds. Nicotine is a lipophilic molecule whose effects
      on neuronal nicotinic acetylcholine receptors (nAChR) have been primarily focused
      on its physiologic impact within the confines of the brain and peripheral nervous
      system. However, recently, many studies have found neuronal nAChRs to be
      expressed on many different nonneuronal cell types throughout the body, where
      increasing evidence suggests they have important roles in determining the
      consequences of nicotine use on multiple organs systems and diseases as diverse
      as ulcerative colitis, chronic pulmonary obstructive disease, and diabetes, as
      well as the neurologic disorders of Parkinson's and Alzheimer's disease. This
      review highlights current evidence for the expression of peripheral nAChRs in
      cells other than neurons and how they participate in fundamental processes, such
      as inflammation. Understanding these processes may offer novel therapeutic
      strategies to approach inflammatory diseases, as well as precautions in the
      design of interventional drugs.

PMID- 16594643
TI  - Microencapsulation of hemoglobin in chitosan-coated alginate microspheres
      prepared by emulsification/internal gelation.
AB  - Chitosan-coated alginate microspheres prepared by emulsification/internal
      gelation were chosen as carriers for a model protein, hemoglobin (Hb), owing to
      nontoxicity of the polymers and mild conditions of the method. The influence of
      process variables related to the emulsification step and microsphere recovering
      and formulation variables, such as alginate gelation and chitosan coating, on the
      size distribution and encapsulation efficiency was studied. The effect of
      microsphere coating as well its drying procedure on the Hb release profile was
      also evaluated. Chitosan coating was applied by either a continuous
      microencapsulation procedure or a 2-stage coating process. Microspheres with a
      mean diameter of less than 30 microm and an encapsulation efficiency above 90%
      were obtained. Calcium alginate cross-linking was optimized by using an
      acid/CaCO(3) molar ratio of 2.5, and microsphere-recovery with acetate buffer led
      to higher encapsulation efficiency. Hb release in gastric fluid was minimal for
      air-dried microspheres. Coating effect revealed a total release of 27% for 2
      stage coated wet microspheres, while other formulations showed an Hb release
      above 50%. Lyophilized microspheres behaved similar to wet microspheres, although
      a higher total protein release was obtained with 2-stage coating. At pH 6.8,
      uncoated microspheres dissolved in less than 1 hour; however, Hb release from air
      dried microspheres was incomplete. Chitosan coating decreased the release rate of
      Hb, but an incomplete release was obtained. The 2-stage coated microspheres
      showed no burst effect, whereas the 1-stage coated microspheres permitted a
      higher protein release.

PMID- 16594644
TI  - Role of animal models in the study of drug-induced hypersensitivity reactions.
AB  - Drug-induced hypersensitivity reactions (DHRs) are a major problem, in large part
      because of their unpredictable nature. If we understood the mechanisms of these
      reactions better, they might be predictable. Their unpredictable nature also
      makes mechanistic studies very difficult, especially prospective clinical
      studies. Animal models are vital to most biomedical research, and they are almost
      the only way to test basic hypotheses of DHRs, such as the involvement of
      reactive metabolites. However, useful animal models of DHRs are rare because DHRs
      are also unpredictable in animals. For example, sulfonamide-induced DHRs in large
      breed dogs appear to be valid because they are very similar to the DHRs that
      occur in humans; however, the incidence is only approximately 0.25%, and large
      breed dogs are difficult to use as an animal model. Two more practical models are
      penicillamine-induced autoimmunity in the Brown Norway rat and nevirapine-induced
      skin rash in rats. The toxicity in these models is clearly immune mediated. In
      other models, such as amodiaquine-induced agranulocytosis/hepatotoxicity and
      halothane-induced hepatotoxicity, the drug induces an immune response but there
      is no clinical toxicity. This finding suggests that regulatory mechanisms usually
      limit toxicity. Many of the basic characteristics of the penicillamine and
      nevirapine models, such as memory and tolerance, are quite different suggesting
      that the mechanisms are also significantly different. More animal models are
      needed to study the range of mechanisms involved in DHRs; without them, progress
      in understanding such reactions is likely to be slow.

PMID- 16594646
TI  - Generation of monoclonal antibodies to cancer/testis (CT) antigen CT10/MAGE-C2.
AB  - CT10/MAGE-C2 is a recently identified antigen that, typically of cancer/testis
      (CT) antigens, can be found in various malignant tumors and in normal adult
      testis. As with many other CT antigens, our knowledge is based mainly on mRNA
      expression data. In the present study, we describe the generation of mAbs to
      CT10/MAGE-C2 for the analysis of its protein expression. Newly generated clones
      were chosen based on their reactivity in ELISA, immunoblotting, and
      immunohistochemistry (IHC). Emphasis was put on the reactivity of newly generated
      reagents on formalin-fixed, paraffin-embedded tissue to ensure their
      applicability to archival material. Eventually we selected two clones, LX-CT10.5
      and LX-CT10.9, that showed intense reactivity to CT10/MAGE-C2 protein and
      CT10/MAGE-C2 mRNA-positive cell lines, but no cross-reactivity with other CT
      antigens. Both mAbs show superior staining characteristics in IHC and are
      applicable to frozen and paraffin sections. In testis, CT10/MAGE-C2 displays the
      typical CT pattern with regard to staining of germ cells, which is intense during
      the early maturation stages. In tumors, we analyzed a limited number of cases
      displaying the typical heterogeneous CT expression pattern. Interestingly,
      immunoreactivity was seen solely in the nucleus: No staining was seen in the
      cytoplasm of tumor cells.

PMID- 16594645
TI  - N-n-alkylnicotinium analogs, a novel class of antagonists at alpha 4 beta 2*
      nicotinic acetylcholine receptors: inhibition of S(-)-nicotine-evoked 86Rb+
      efflux from rat thalamic synaptosomes.
AB  - Pyridine N-n-alkylation of S(-)-nicotine (NIC) affords N-n-alkylnicotinium
      analogs, previously shown to competitively inhibit [(3)H]NIC binding and interact
      with alpha4beta2* nicotinic receptors (nAChRs). The present study determined the
      ability of the analogs to inhibit NIC-evoked (86)Rb(+) efflux from rat thalamic
      synaptosomes to assess functional interaction with alpha4beta2* nAChRs. In a
      concentration-dependent manner, NIC evoked (86)Rb(+) efflux (EC(50) = 170
      nmol/L). Analog-induced inhibition of NIC-evoked (86)Rb(+) efflux varied over a
      approximately 450-fold range. Analogs with long n-alkyl chain lengths (C(9)
      C(12)) inhibited efflux in the low nmol/L range (IC(50) = 9-20 nmol/L), similar
      to dihydro-beta-erythroidine (IC(50) = 19 nmol/L). Compounds with shorter n-alkyl
      chain lengths (C(1)-C(8)) produced inhibition in the low micromol/L range (IC(50)
      = 3-12 micromol/L). C(10) and C(12) analogs completely inhibited NIC-evoked
      efflux, whereas C(1-9) analogs produced maximal inhibition of only 10% to 60%.
      While the C(10) analog N-n-decylnicotinium iodide (NDNI) did not produce
      significant inhibition of NIC-evoked dopamine release in previously reported
      studies, NDNI possesses high affinity for [(3)H]NIC binding sites (K(i) = 90
      nmol/L) and is a potent and efficacious inhibitor of NIC-evoked (86)Rb(+) efflux
      as demonstrated in the current studies. Thus, NDNI is a competitive, selective
      antagonist at alpha4beta2* nAChRs.

PMID- 16594647
TI  - Supramolecular probe for bicarbonate exhibiting anomalous pyrene fluorescence in
      aqueous media.
AB  - Highly selective HCO3- sensing is realized in a pH 8.6 aqueous solution on the
      basis of the HCO3--induced anomalous pyrene fluorescence of an association dimer
      that consists of pyrene-appended gamma-cyclodextrins having a triamine linker.
      The anomalous fluorescence that is produced by the HCO3--induced twisted
      conformation of the pyrene residues in the association dimer is insensitive to
      the presence of other anions.

PMID- 16594648
TI  - Fluorescent sensors for organophosphorus nerve agent mimics.
AB  - We present a small molecule sensor that provides an optical response to the
      presence of an organophosphorus (OP)-containing nerve agent mimic. The design
      contains three key features: a primary alcohol, a tertiary amine in close
      proximity to the alcohol, and a fluorescent group used as the optical readout. In
      the sensor's rest state, the lone pair of electrons of the basic amine quenches
      the fluorescence of the nearby fluorophore through photoinduced electron transfer
      (PET). Exposure to an OP nerve agent mimic triggers phosphorylation of the
      primary alcohol followed rapidly by an intramolecular substitution reaction as
      the amine displaces the created phosphate. The quaternized ammonium salt produced
      by this cyclization reaction no longer possesses a lone pair of electrons, and a
      fluorescence readout is observed as the nonradiative PET quenching pathway of the
      fluorophore is shut down.

PMID- 16594649
TI  - Controlled encapsidation of gold nanoparticles by a viral protein shell.
AB  - Icosahedral virus capsids demonstrate a high degree of selectivity in packaging
      cognate nucleic acid components during assembly. This packaging specificity, when
      integrated as part of a nanotechnological protocol, has the potential to
      encapsidate a wide array of foreign materials for delivery of therapeutics or
      biosensors into target cells. Red clover necrotic mosaic virus (RCNMV)
      exclusively packages two genomic ssRNAs initiated by a specific protein:RNA
      interaction between the RCNMV coat protein (CP) and the viral RNA origin of
      assembly (OAS) element. In the present work, an oligonucleotide mimic of the
      RCNMV OAS sequences is attached to Au nanoparticles as a recognition signal to
      initiate the virion-like assembly by RCNMV CP. Covalent linkage of the OAS to Au
      functions as a trigger for specific encapsidation and demonstrates that foreign
      cargo can be packaged into RCNMV virions.

PMID- 16594650
TI  - Rigid molecular architectures that comprise a 1,3,5-trisubstituted benzene core
      and three oligoaryleneethynylene arms: light-emitting characteristics and pi
      conjugation between the arms.
AB  - In view of increasing interest in light-emitting materials, we have investigated
      the light-emitting characteristics and occurrence of conjugation between arms of
      star-shaped rigid molecules that comprise a 1,3,5-triethynylbenzene core and
      methoxy group-substituted oligo(p-phenylethynylene) arms. Consequently, we
      achieved the ultimate goal (Phif approximately 1.0, log epsilon > 5) for organic
      molecules with respect to light-emitting ability by creating very intense violet
      blue (8, Phif = 0.97, log epsilon = 5.11) and blue (9, Phif = 0.98, log epsilon =
      5.29) bright light-emitters. Also, pi conjugation was found to occur between the
      arms of 9 despite the meta-substituted system. We found a linear relationship of
      kr (with positive slope) and kd (with negative slope) with the number of
      dimethoxyphenyleneethynylene units for MMPT (4, 6, 8) and DMPT (5, 7, 9)
      homologues and the contrasting solvent effect on lambdaem of 8 and 9. It is also
      interesting that lambdaabs, epsilon, lambdaem, and Phif of 9 are greater than
      those of the corresponding banana- and rod-shaped molecules.

PMID- 16594651
TI  - Alkenylsilane effects on organotitanium-catalyzed ethylene polymerization. Toward
      simultaneous polyolefin branch and functional group introduction.
AB  - The comonomer 5-hexenylsilane is introduced into organotitanium-mediated ethylene
      polymerizations to produce silane-terminated ethylene/5-hexenylsilane copolymers.
      The resulting polymers were characterized by 1H and 13C NMR, GPC, and DSC. High
      activities (up to 107 g polymer/(mol Ti.atm ethylene.h)) and narrow
      polydispersities are observed in the polymerization/chain transfer process.
      Ethylene/5-hexenylsilane copolymer molecular weights are found to be inversely
      proportional to 5-hexenylsilane concentration, supporting a silanolytic chain
      transfer mechanism. Control experiments indicate that chain transfer mechanism by
      5-hexenylsilane is significantly more efficient than that of n-hexylsilane for
      organotitanium-mediated ethylene polymerization. The present study represents the
      first case in which a functionalized comonomer is efficiently used to effect both
      propagation and chain transfer chemistry during olefin polymerization.

PMID- 16594652
TI  - From gene to HSQC in under five hours: high-throughput NMR proteomics.
AB  - A simple, rapid, in vitro cell-free protein expression system, Expressway NMR, is
      introduced and used to express the small ubiquitin-related modifier protein SUMO
      1. This 12 kDa molecule is challenging for NMR as it has limited solubility and
      requires relatively high salt (200 mM) for stability in solution. Starting with
      the gene, the cell-free system, and milligram amounts of nitrogen-15 isotopically
      enriched amino acids, sufficient protein is produced in 4 h to obtain a high
      resolution 2D HSQC spectrum of the protein in 40 min. This time would be closer
      to 10 min with the aid of a higher sensitivity salt-tolerant cryogenic NMR probe.
      With all protein purification steps included, and aggressive data processing
      using the filter diagonalization method (FDM), it is but 6 h from gene to
      heteronuclear single quantum coherence (HSQC). As the cell-free system is nearly
      background-free, it is also possible to work with the crude reaction mixture, in
      which case only a total of 5 h is required. Sample stability over time, whether
      crude extract or purified, was notable, with no significant change in the 15N-1H
      HSQC spectrum over 6 months at 4 degrees C (300 muM, pH 6.1, capped NMR tube).
      The combination of a turnkey, high-yield, protease-free in vitro protein
      expression system, an optimized sensitivity-enhanced HSQC pulse sequence, and FDM
      processing makes this scheme an attractive first step to rapidly assess the
      suitability of proteins for complete solution structure determination.

PMID- 16594654
TI  - Aerosol-assisted self-assembly of single-crystal core/nanoporous shell particles
      as model controlled release capsules.
AB  - Single-crystal NaCl core/nanoporous shell particles have been synthesized by
      evaporation-induced self-assembly. By variation of the hydrophobicity of the
      mesoporous shell, we can control the release rates by over 4 orders of magnitude.

PMID- 16594653
TI  - Effect of Pd nanoparticle size on the catalytic hydrogenation of allyl alcohol.
AB  - We report a particle size dependence for the rate of hydrogenation of allyl
      alcohol using 1.3-1.9 nm Pd dendrimer-encapsulated nanoparticle (DEN) catalysts.
      For particles with diameters of <1.5 nm and containing <147 Pd atoms, the
      modulation in catalytic activity is due to the electronic properties of the
      particle. For the larger particles, 1.5-1.9 nm in diameter and containing an
      average of 147-250 Pd atoms, the size effect is a result of geometrical
      constraints. Specifically, the hydrogenation reaction is shown to occur
      preferentially on the face atoms of the larger nanoparticles.

PMID- 16594655
TI  - Orbital energetics and molecular recognition.
AB  - We present preliminary data demonstrating that orbital eigenenergy fluctuation
      recorded in the course of ab initio molecular dynamics calculations may contain
      information relevant in determining molecular behavior and recognition. A simple
      scheme is presented that maps these data to molecular descriptors. Using
      computational drug design as the context, these descriptors are compared with
      previous electronic eigenvalue descriptor methods with encouraging results.

PMID- 16594657
TI  - Electron hopping dynamics in Au38 nanoparticle langmuir monolayers at the
      air/water interface.
AB  - The electron-transfer dynamics between nanoparticles has been studied as a
      function of interparticle distance by in situ voltammetry of well-defined
      monolayers of a metal quantum dot nanoparticle Au38(hexanethiolate)24. The
      interparticle distance is precisely controlled by the Langmuir technique and
      addition of various lengths of dithiol linkers (HS(CH2)nSH; n = 5, 6, 8, and 9).
      Voltammograms of Au38 monolayers display a well-defined single-electron charging
      peak that increases remarkably with decreasing the interparticle distance. The
      diffusion coefficient and rate constant calculated from the peak current for core
      core electron hopping reaction both exponentially increase respectively, from 3.3
      x 10-10 to 5.2 x 10-9 cm2/s and 2.2 x 104 to 5.0 x 105 s-1 as the distance
      decreases from 13.3 to 9.5 A and then levels off at 8.0 A. These rate constants
      are in good agreement with the literature values, demonstrating that the present
      experimental approach provides a powerful way to investigate the correlation
      between the electron-transfer dynamics and nanoparticle assembly structure.

PMID- 16594656
TI  - A simple tagging system for protein encapsulation.
AB  - Molecular containers that encapsulate specific cargo can be useful for many
      natural and non-natural processes. We report a simple system, based on charge
      complementarity, for the encapsulation of appropriately tagged proteins within an
      engineered, proteinaceous capsid. Four negative charges per monomer were added to
      the lumazine synthase from Aquifex aeolicus (AaLS). The capsids formed by the
      engineered AaLS associate with green fluorescent protein bearing a positively
      charged deca-arginine tag upon coproduction in Escherichia coli. Analytical
      ultracentrifugation and scanning force microscopy studies indicated that the
      engineered AaLS retains the ability to form capsids, but that their average size
      was substantially increased. The success of this strategy demonstrates that both
      the container and guest components of protein-based encapsulation systems can be
      convergently designed in a straightforward manner, which may help to extend their
      versatility.

PMID- 16594658
TI  - A unidirectional energy transfer cascade process in a ruthenium junction self
      assembled by alpha- and beta-cyclodextrins.
AB  - A Ru(II) complex, Ru(alpha2beta), with a trisbipyridyl core and two different
      receptor sites, alpha- and beta-cyclodextrins, acts as a junction to recognize
      photoactive guests based on anthracene, Anth, and Os(II), Os-ada, in aqueous
      solution. Upon light excitation of the self-assembled system
      Anth.Ru(alpha2beta).Os-ada, an energy cascade process takes place from the Anth
      guest to the Ru(alpha2beta) core, and subsequently, the energy is funneled to the
      Os-ada guest. The rates of the two photoinduced processes are determined by time
      resolved emission and transient absorption spectroscopic techniques. The system
      introduces a directed self-assembly approach to unidirectional wires that can
      lead to nanosized arrays by judicious selection of the individual components.

PMID- 16594659
TI  - Engineering a rhodopsin protein mimic.
AB  - Due to the difficulties in handling and manipulating membrane-bound proteins,
      such as rhodopsin, and the lack of crystallographic information on the cone
      opsins, we have opted to engineer a protein mimic of the transmembrane G-protein
      coupled receptor. Human cellular retinoic acid binding protein (CRABPII), a well
      studied and characterized protein, has been reengineered into a protein that now
      will bind retinal as a protonated Schiff base with high binding affinity (Kd = 2
      nM) mimicking that of rhodopsin.

PMID- 16594660
TI  - A second transition state for chain transfer to monomer in olefin polymerization
      promoted by group 4 metal catalysts.
AB  - beta-Hydrogen transfer (BHT) to monomer is the dominant chain termination pathway
      for olefin polymerization promoted by group 4 metal catalysts. The transition
      state (TSA) for BHT studied in earlier work is characterized by a strong metal
      hydrogen interaction. Our theoretical study of a series of homogeneous single
      site polymerization catalysts reveals the existence of a second transition state
      (TSC), competitive with TSA, which has no direct metal-hydrogen interaction and
      strongly resembles that for the main-group metal aluminum. The balance between
      the two reaction paths is sensitive to choice of metal and ligand structure.

PMID- 16594661
TI  - Conformational flexibility in the peripheral site of Torpedo californica
      acetylcholinesterase revealed by the complex structure with a bifunctional
      inhibitor.
AB  - The X-ray crystallographic structure of Torpedo californica acetylcholinesterase
      (TcAChE) in complex with the bifunctional inhibitor NF595, a potentially new anti
      Alzheimer drug, has been solved. For the first time in TcAChE, a major
      conformational change in the peripheral-site tryptophan residue is observed upon
      complexation. The observed conformational flexibility highlights the dynamic
      nature of protein structures and is of importance for structure-based drug
      design.

PMID- 16594662
TI  - Metal-chelate dye-controlled organization of Cd32S14(SPh)40(4-) nanoclusters into
      three-dimensional molecular and covalent open architecture.
AB  - Chalcogenide II-VI nanoclusters are usually prepared as isolated clusters and
      have defied numerous efforts to join them into covalent open-framework
      architecture with conventional templating methods such as protonated amines or
      inorganic cations commonly used to direct the formation of porous frameworks.
      Herein, we report the first templated synthesis of II-VI covalent superlattices
      from large II-VI tetrahedral clusters (i.e., [Cd32S14(SPh)38]2-). Our method
      takes advantage of low charge density of metal-chelate dyes that is a unique
      match with three-dimensional II-VI semiconductor frameworks in charge density,
      surface hydrophilicity-hydrophobicity, and spatial organization. In addition,
      metal-chelate dyes also serve to tune the optical properties of resulting dye
      semiconductor composite materials.

PMID- 16594663
TI  - Unexpected deacetylation mechanism suggested by a density functional theory QM/MM
      study of histone-deacetylase-like protein.
AB  - To characterize the catalytic mechanism for zinc-dependent histone deacetylases
      (HDAC), we have carried out density functional theory QM/MM studies on the
      deacetylation reaction catalyzed by a histone-deacetylase-like protein (HDLP).
      The calculation results do not support the previous mechanistic hypothesis, but
      suggest a lower protonation state for the active site as well as a 4-fold zinc
      coordination during the reaction process. To characterize such mechanistic
      difference is not only significant for our fundamental understanding of its inner
      workings but also crucial for the design of HDAC inhibitors.

PMID- 16594664
TI  - One-dimensional energy/electron transfer through a helical channel.
AB  - We have synthesized A-D-A-type linear chain chromophores based on oligo(phenylene
      vinylene) as an electron donor (D) and several electron/energy acceptors (A),
      which are linked by an alkyl spacer with various lengths and are processed for a
      helical encapsulation with amylose. Photoinduced electron/energy transfers
      (eT/ET) of the chromophores are investigated in the presence and absence of the
      helical encapsulation with respect to D-A distance. Fluorescence intensity of the
      free chromophores is unusually small, not due to the advancement of eT/ET but
      most likely to self-quenching by aggregation and/or conformational flexibility in
      solution. By contrast, the helically encapsulated chromophores exhibit highly
      efficient eT/ET over a long D-A distance and a well-defined distance effect
      depending on the acceptor strength.

PMID- 16594665
TI  - Multi-frequency high-field EPR study of iron centers in malarial pigments.
AB  - The multi-frequency high-field electron paramagnetic resonance (HFEPR) was used
      to study the magnetic properties of malarial pigment hemozoin and its synthetic
      analogue, beta-hematin. (FeIII-protoporphyrin-IX)2 dimers containing five
      coordinate high-spin FeIII, S = 5/2, are the building blocks of these pigments.
      The fit of EPR spectra that were acquired in an unprecedented wide range of
      microwave frequencies of 34 and 94 GHz for hemozoin and 27-500 GHz for beta
      hematin yielded a complete set of intrinsic spin Hamiltonian parameters: D =
      +5.85(1) cm-1, E = 0, g perpendicular = 1.95(1), g parallel = 2.00(1). These
      results point to the existence of largely axial symmetry of the iron environment
      in the bulk phase of hemozoin and beta-hematin.

PMID- 16594666
TI  - A mechanism-based inactivator for histone demethylase LSD1.
AB  - Histone demethylase LSD1 is a flavin-dependent amine oxidase that catalyzes the
      oxidative removal of one or two methyl groups from the methyl-lysine-4 side chain
      of histone H3. We have designed and synthesized two peptide-based inhibitor
      analogues that block LSD1. One of these inhibitors, compound 1, contains a
      propargylamine functionality and shows time-dependent inactivation of LSD1.
      Peptide substrate, diMeK4H3-21, protected LSD1 against inactivation by 1 in a
      concentration-dependent fashion. Mass spectrometric analysis showed that 1 forms
      a covalent interaction with FAD. Compound 1 did not detectably inhibit monoamine
      oxidase B in the concentration range studied. Compound 1 is thus a selective,
      mechanism-based inactivator of LSD1 and is likely to serve as a useful tool in
      the study of histone modifications and chromatin remodeling.

PMID- 16594667
TI  - New helical foldamers: heterogeneous backbones with 1:2 and 2:1 alpha:beta-amino
      acid residue patterns.
AB  - Foldamers, oligomers with strong folding propensities, are subjects of growing
      interest because such compounds offer unique scaffolds for the development of
      molecular function. We report two new foldamer classes, oligopeptides with
      regular 1:2 or 2:1 patterns of alpha- and beta-amino acid residues. Two distinct
      helical conformations are detected via 2D NMR in methanol for each backbone. One
      of the helices for each backbone is characterized via X-ray crystallography.

PMID- 16594668
TI  - Spatially selective guided growth of high-coverage arrays and random networks of
      single-walled carbon nanotubes and their integration into electronic devices.
AB  - The chemical vapor deposition growth of unusual arrangements of single-walled
      carbon nanotubes (SWNTs) by the combined of use patterned catalysts and quartz
      substrates is reported. Nearly perfectly aligned, high-coverage arrays of SWNTs
      can be generated in this manner. High-coverage random networks of SWNTs can also
      be created in the same growth step, with good spatial alignment and electrical
      interfaces to the aligned arrays. Tubes with these geometries are ideally suited
      to applications in thin-film electronic devices. We demonstrate this possibility
      through the construction of thin-film-type transistors in which the random
      networks form the source and drain electrodes and the aligned arrays form the
      channel.

PMID- 16594670
TI  - Formation of highly ordered mesoporous titania films consisting of crystalline
      nanopillars with inverse mesospace by structural transformation.
AB  - Highly ordered mesoporous titania films consisting of crystalline nanopillars
      with open-spaced, perpendicular, and continuous porosity have been prepared via
      structural transformation from a 3D hexagonal mesostructure during the thermal
      treatment. The mechanism of the structural transformation is explained by the
      crystallization of the titania framework and the large contraction of the initial
      3D hexagonal mesostructured film upon calcination. This structural transformation
      provides a new approach to generate mesoporous thin-film materials with unique
      structures.

PMID- 16594669
TI  - Transglutaminase-catalyzed site-specific conjugation of small-molecule probes to
      proteins in vitro and on the surface of living cells.
AB  - Site-specific protein labeling methods allow cell biologists to access the vast
      array of existing chemical probes for the study of specific proteins of interest
      in the live cell context. Here we describe the use of the transglutaminase enzyme
      from guinea pig liver (gpTGase), whose natural function is to cross-link
      glutamine and lysine side chains, to covalently conjugate various small-molecule
      probes to recombinant proteins fused to a 6- or 7-amino acid transglutaminase
      recognition sequence, called a Q-tag. We demonstrate labeling of Q-tag fusion
      proteins both in vitro and on the surface of living mammalian cells with biotin,
      fluorophores, and a benzophenone photoaffinity probe. To illustrate the utility
      of this labeling, we tagged the NF-kappaB p50 transcription factor with
      benzophenone, cross-linked with UV light, and observed increased levels of p50
      homodimerization in the presence of DNA and the binding protein myotrophin.

PMID- 16594671
TI  - Total synthesis of enantiopure beta-D-mannosyl phosphomycoketides from
      Mycobacterium tuberculosis.
AB  - The first stereoselective total synthesis of a beta-d-mannosyl phosphomycoketide
      is reported. To introduce the stereogenic centers in the chain, three linear
      chiral building blocks were prepared using two different asymmetric catalytic
      conjugate addition protocols. Coupling of the various linear fragments was
      affected using a Julia-Kocienski sequence. This approach constitutes a general
      and convergent method for the construction of saturated oligoisoprenoid chains of
      any length and stereochemistry. In addition, an alternative approach for the
      formation of the difficult beta-mannosyl phosphate linkage was shown to be
      successful. Biological evalutation of the all-S compound revealed that its
      antigenic potency for T cells is identical to that of the natural product. This
      result implies that the fine structure of the lipid part has a strong influence
      on biological activity and that the T cell response is discriminating between
      different stereoisomers.

PMID- 16594672
TI  - Highly luminescent gels and mesogens based on elaborated borondipyrromethenes.
AB  - Supramolecular gels and liquid-crystalline materials containing
      borondipyrromethene (F-Bodipy) are a new class of highly luminescent materials
      built by attachment of long-chain alkoxydiacylamido scaffoldings to
      boradiazaindacene templates. Robust gels were formed in nonane, and luminescence
      spectroscopy was used to probe the aggregation processes of the flat indacene
      cores. Coincidently, columnar mesophase was obtained from the pure material over
      a wide temperature range, allowing textural observations by fluorescence
      microscopy.

PMID- 16594673
TI  - Light-driven OR and XOR programmable chemical logic gates.
AB  - Photoelectrodes made of nanocrystalline titanium dioxide modified with various
      pentacyanoferrates exhibit unique photoelectrochemical properties; photocurrent
      direction can be switched from anodic to cathodic and vice versa upon changes in
      photoelectrode potential and incident light wavelength (PhotoElectrochemical
      Photocurrent Switching, PEPS effect). At certain potentials, anodic photocurrent
      generated upon UV irradiation has the same intensity as the cathodic photocurrent
      generated upon visible irradiation. Under these conditions, simultaneous
      irradiation with UV and visible light results in compensation of anodic and
      cathodic photocurrents, and zero net photocurrent is observed. This process can
      be used for construction of unique light-driven chemical logic gates.

PMID- 16594674
TI  - Electrochemical and homogeneous proton-coupled electron transfers: concerted
      pathways in the one-electron oxidation of a phenol coupled with an intramolecular
      amine-driven proton transfer.
AB  - Proton-coupled electron transfers currently attract considerable attention in
      view of their likely involvement in many natural processes. Electrochemistry,
      through techniques such as cyclic voltammetry, is an efficient way of
      investigating the reaction mechanism of these reactions, and deciding whether
      proton and electron transfers are concerted or occur in a stepwise manner. The
      oxidation of an ortho-substituted 4,6-di (tert-butyl)-phenol in which the
      phenolic hydrogen atom is transferred during the reaction to the nitrogen atom of
      a nearby amine is taken as illustrative example. A careful analysis of the cyclic
      voltammetric responses obtained with this compound and its OD derivative allows,
      after estimation of the various thermodynamic parameters, ruling out the
      occurrence of the square scheme mechanism involving the proton-electron and
      electron-proton sequences. Simulation and comparison of the rate constant and H/D
      kinetic isotope effect with theoretical predictions show that the experimental
      value of the preexponential factor is ca. 1 order of magnitude larger than the
      theoretical value. Detailed calculations suggest that an electric field effect is
      responsible for this discrepancy.

PMID- 16594675
TI  - Enabling gate dielectric design for all solution-processed, high-performance,
      flexible organic thin-film transistors.
AB  - A novel solution-processed, compositionally and structurally stable dual-layer
      gate dielectric composed of a UV-cured poly(4-vinyl phenol)-co-poly(methyl
      methacrylate) bottom layer and a thermally cross-linked poly(methyl
      silsesquioxane) top layer for organic thin-film transistors is described. This
      gate dielectric design, coupled with compatible solution-processable
      semiconductor and conductor materials, has enabled fabrication of all solution
      processed, high-performance organic thin-film transistors on flexible substrates.
      High field-effect mobility and current on/off ratio, together with other
      desirable transistor properties, are demonstrated.

PMID- 16594676
TI  - Triazabicyclodecene: a simple bifunctional organocatalyst for acyl transfer and
      ring-opening polymerization of cyclic esters.
AB  - 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) is an effective organocatalyst for acyl
      transfer as well as the ring-opening polymerization of cyclic esters. Its high
      activity is attributed to its ability to simultaneously activate both esters and
      alcohols, as demonstrated in a model reaction. This unique mechanism makes TBD a
      remarkably simple example of a bifunctional catalyst. The simplicity of the
      reaction conditions, the ready commercial availability of the catalyst, and its
      high activity provide an accessible methodology to allow future studies of tailor
      made polyesters.

PMID- 16594677
TI  - Hydroacylation of activated ketones catalyzed by N-heterocyclic carbenes.
AB  - N-heterocyclic carbenes derived from triazolium salts are effective catalysts
      between 10 and 15 mol % for the hydroacylation of activated ketones. The reducing
      equivalent is generated via the interaction of a nucleophilic carbene species and
      an aromatic aldehyde. The subsequent alcohol product can undergo an acylation
      event with the resulting acyl heteroazolium intermediate formed in situ between
      the NHC and the aldehyde. This unprecedented multiple bond-forming reaction can
      accommodate aromatic aldehydes as the hydride source and various electron
      deficient ketones. Preliminary mechanistic evidence indicates that the reduction
      and acylation steps are sequential operations. The intramolecular variant of this
      organocatalytic reaction affords benzofuranones in good yield.

PMID- 16594678
TI  - Microcontainers with electrochemically reversible permeability.
AB  - The present study demonstrates a novel application of polyelectrolyte
      microcapsules as microcontainers with electrochemically reversible flux of redox
      active materials into and out of the capsule volume. Incorporation of the
      capsules inside the conducting polymer (polypyrrole) film results in a new
      composite electrode combining electrocatalytic and conducting properties of the
      polypyrrole with the storage and release properties of the capsules. This
      electrode, if loaded with electrochemical fuels, can possess electrochemically
      controlled switching between "open/closed" states of the capsule shell and be of
      practical interest for a new type of chemically rechargeable batteries or fuel
      cells. A special explanation for the potential depending loading and unloading of
      the capsule inner volume may be related to the fact that the polyelectrolyte
      capsules experience a potential gradient in the polypyrrole matrix within which
      the polyions of the shell can be moved.

PMID- 16594679
TI  - Magnetic tuning of the electrochemical reactivity through controlled surface
      orientation of catalytic nanowires.
AB  - Nanowires have received considerable attention owing to their broad potential
      applications. We report here on the application of nanowires for magnetic control
      of the electrochemical reactivity and demonstrate how one can modulate the
      electrocatalytic activity by orienting catalytic nanowires at different angles.
      Unlike early "on/off" magnetic switching studies based on functionalized magnetic
      spheres, the present magnetoswitchable protocol relies on modulating the
      electrochemical reactivity without removing the magnetic material from the
      surface. Such behavior is attributed to the reversible blocking of the redox
      processes and to changes in the tortuosity-dependent flux rate. The nanowire
      based magnetoswitchable protocol may be extremely useful for adjusting the
      electrochemical reactivity, such as for tuning the power output of fuel cells
      (rather than switching the power on/off).

PMID- 16594681
TI  - Regiospecific radical polymerization of a tetrasubstituted ethylene monomer with
      molecular oxygen for the synthesis of a new degradable polymer.
AB  - A new class of degradable polymers is obtained from a diene monomer and molecular
      oxygen as the starting materials via a highly controlled radical copolymerization
      process. We now report the regiospecific copolymerization of a tetrasubstituted
      ethylene monomer with oxygen. Theoretical calculations support the highly
      selective propagations observed during the polymerization. The key steps are the
      regiospecific reactions of a peroxy radical to diene monomers and an allyl
      radical to molecular oxygen. The well-controlled molecular structure of the
      resulting polymer leads to the aldehyde-free degradation products during
      degradation by various stimuli, such as heating.

PMID- 16594680
TI  - Metal-mediated efficient synthesis, structural characterization, and skeletal
      rearrangement of octasubstituted semibullvalenes.
AB  - The first metal-mediated efficient synthesis of octasubstituted semibullvalenes,
      including octaalkyl and mixed tetraalkyl and tetraphenyl derivatives, was
      developed. The structures of these semibullvalenes were determined by single
      crystal X-ray structural analysis. Their intramolecular skeletal rearrangement
      and reaction chemistry were investigated.

PMID- 16594682
TI  - New chiral synthons for efficient introduction of bispropionates via
      stereospecific oxonia-cope rearrangements.
AB  - Compounds 1 and 2 are novel synthons for bispropionate synthesis, undergoing
      stereospecific Lewis acid-catalyzed transfer of the bispropionate unit with a
      variety of aldehydes, including alpha-chiral aldehydes. Thus 1 leads to the E
      alkene bispropionate 3 with anti-stereochemistry, whereas diastereomer 2 gives
      the Z-alkene product 4, under mild conditions and with complete
      stereospecificity. The efficacy of this methodology is demonstrated in a short
      synthesis of invictolide beginning with 2 and (R)-2-methylpentanal.

PMID- 16594683
TI  - In situ synthesis of mixed-valent manganese oxide nanocrystals: an in situ
      synchrotron X-ray diffraction study.
AB  - Phase transformations of materials can be studied by in situ synchrotron X-ray
      diffraction. However, most reported in situ synchrotron XRD studies focus on
      solid state/gel systems by measuring phase/structure changes during application
      of pressure or heat. Phase transformations during material synthesis and their
      applications, especially in wet chemistry processes with different media, have
      not drawn much attention. Here, using manganese oxides as examples, we report the
      successful characterization of phase transformations in in situ hydrothermal
      synthesis conditions by the in situ synchrotron XRD method using a
      quartz/sapphire capillary tube as the synthesis reactor. The results were used
      for better design of materials with controlled structures and properties. This
      method can be generally used for synthesis of manganese oxides as well as for in
      situ characterization of other material syntheses using hydrothermal, sol-gel,
      and other methods. In addition, catalytic processes in liquid-solid, gas-solid,
      and solid-solid systems can also be studied in such an in situ way so that
      catalytic mechanisms can be better understood and catalyst synthesis and
      catalytic processes can be optimized.

PMID- 16594684
TI  - The genetic incorporation of a distance probe into proteins in Escherichia coli.
AB  - The unnatural amino acid p-nitrophenylalanine (pNO2-Phe) was genetically
      introduced into proteins in Escherichia coli in response to the amber nonsense
      codon with high fidelity and efficiency by means of an evolved tRNA/aminoacyl
      tRNA synthetase pair from Methanocuccus jannaschii. It was shown that pNO2-Phe
      efficiently quenches the intrinsic fluorescence of Trp in a distance-dependent
      manner in a model GCN4 basic region leucine zipper (bZIP) protein. Thus, the pNO2
      Phe/Trp pair should be a useful biophysical probe of protein structure and
      function.

PMID- 16594685
TI  - Nanoscale phase separation in mixed poly(tert-butyl acrylate)/polystyrene brushes
      on silica nanoparticles under equilibrium melt conditions.
AB  - This communication reports on the study of microphase separation of well-defined
      mixed poly(tert-butyl acrylate) (PtBA)/polystyrene (PS) brushes on silica
      nanoparticles under equilibrium melt conditions. Mixed PtBA/PS brushes were
      synthesized from an asymmetric, difunctional initiator-terminated self-assembled
      monolayer by combining atom transfer radical polymerization and nitroxide
      mediated radical polymerization. Two symmetric PtBA/PS mixed brush samples with
      different molecular weights were used in this study and were thermally annealed
      in vacuum at 150 degrees C. For the mixed brushes with number average molecular
      weights (Mn) of 24 200 g/mol for PtBA and 23 000 g/mol for PS, two glass
      transitions were observed in the differential scanning calorimetry analysis.
      Transmission electron microscopy study showed that the two grafted polymers
      underwent a lateral microphase separation, forming a random worm-like pattern
      with a feature size of approximately 10 nm on the silica particle surfaces. In
      contrast, the mixed brushes with a Mn of 10,400 g/mol for PtBA and 11,900 g/mol
      for PS did not microphase separate. Although the mixed brushes are on curved
      substrates, this work provides results consistent with the theoretical prediction
      that symmetric mixed homopolymer brushes undergo lateral rather than vertical
      phase separation under equilibrium melt conditions.

PMID- 16594686
TI  - [3,3]-rearrangements of phosphonium ylides.
AB  - Allylic phosphonium ylides are readily generated by the combination of an allylic
      alcohol, a carbene, and a chlorophosphite. Here we demonstrate that these
      intermediates undergo a thermal [3,3]-rearrangement to provide single isomers of
      homoallylic phosphonates in good to excellent yields. This new reaction manifold
      for phosphorus ylides is tolerant of a range of substitution patterns on the
      reactants and provides access to structurally complex intermediates for the
      synthesis of enzyme inhibitors, aminophosphonic acids, and natural products.

PMID- 16594687
TI  - Amino acid-bearing ROMP polymers with a stereoregular backbone.
AB  - The ruthenium-catalyzed ring-opening polymerization (ROMP) of 1
      cyclobutenecarbonyl glycine methyl ester provides translationally invariant, head
      to-tail ordered polymers. This polybutadiene backbone contains (within the limits
      of detection) only E-trisubstituted olefins, and it has no stereocenters that
      would serve as a source of structural ambiguities. Characterization of the
      polymer products indicates that they have polydispersities ranging from 1.2 to
      1.6 and suggests that they are the products of a "living" polymerization. 1
      Cyclobutenecarboxamide-derived ROMP polymers are excellent prospects for
      applications that require stereoregular chains functionalized with polar ligands.

PMID- 16594689
TI  - Translucent thin film Fe2O3 photoanodes for efficient water splitting by
      sunlight: nanostructure-directing effect of Si-doping.
AB  - Thin, silicon-doped nanocrystalline alpha-Fe2O3 films have been deposited on F
      doped SnO2 substrates by ultrasonic spray pyrolysis and chemical vapor deposition
      at atmospheric pressure. The photocatalytic activity of these films with regard
      to photoelectrochemical water oxidation was measured at pH 13.6 under simulated
      AM 1.5 global sunlight. The photoanodes prepared by USP and APCVD gave 1.17 and
      1.45 mA/cm2, respectively, at 1.23 V vs RHE. The morphology of the alpha-Fe2O3
      was strongly influenced by the silicon doping, decreasing the feature size of the
      mesoscopic film. The silicon-doped alpha-Fe2O3 nano-leaflets show a preferred
      orientation with the (001) basal plane normal to the substrate. The best
      performing photoanode would yield a solar-to-chemical conversion efficiency of
      2.1% in a tandem device using two dye-sensitized solar cells in series.

PMID- 16594690
TI  - 1,1'-Binaphthyl-2,2'-diyl phosphoroselenoyl chloride as a chiral molecular tool
      for the preparation of enantiomerically pure alcohols and amines.
AB  - Enantiomerically pure phosphoroselenoyl chloride bearing a binaphthyl group was
      synthesized. This phosphoroselenoyl chloride was used to discriminate and resolve
      simple secondary alcohols. Stereospecific conversions of diastereomerically pure
      phosphoroselenoic acid esters, obtained by reaction of the chloride with simple
      secondary alcohols, to enantiomerically pure alcohols and amines were also
      achieved.

PMID- 16594691
TI  - Enantioselective synthesis of axially chiral anilides through rhodium-catalyzed
      [2+2+2] cycloaddition of 1,6-diynes with trimethylsilylynamides.
AB  - We have developed a rhodium-catalyzed enantioselective intermolecular [2+2+2]
      cycloaddition of 1,6-diynes with trimethylsilylynamides for the synthesis of
      axially chiral anilides. The axial chirality is constructed at the formation of
      benzene rings with high enantioselectivity (up to 98% ee). It should be noted
      that the present reaction employs the readily prepared trimethylsilylynamides
      starting from commercially available bis(trimethysilyl)acetylene and the
      trimethylsilyl group of the product anilides is expected to be utilized for
      further functionalization.

PMID- 16594688
TI  - Cytochrome p450 compound I.
AB  - Cytochrome P450 enzymes (P450s) comprise a large class of enzymes that effect
      numerous oxidations in nature. The active oxidants in P450s are thought to be
      iron(IV)-oxo porphyrin radical cations termed Compounds I, and these
      intermediates have been sought since the discovery of P450s 40 years ago. We
      report formation of the Compound I derivative of a P450 enzyme by laser flash
      photolysis oxidation of the corresponding Compound II species, an iron(IV)-oxo
      neutral porphyrin intermediate. The Compound II derivative in turn was produced
      by oxidation of the P450 with peroxynitrite, which effected a net one-electron,
      oxo-transfer reaction to the iron(III) atom of the resting enzyme. For the P450
      studied in this work, CYP119 from the thermophile Sulfolobus solfactaricus, the
      P450 Compound II derivative was stable for seconds at ambient temperature, and
      the Compound I transient decayed with a lifetime of ca. 200 ms.

PMID- 16594692
TI  - Direct boronation of allyl alcohols with diboronic acid using palladium pincer
      complex catalysis. A remarkably facile allylic displacement of the hydroxy group
      under mild reaction conditions.
AB  - Allyl alcohols were converted to allyl boronic acids and subsequently to
      trifluoro(allyl)borates with tetrahydroxy diboron using palladium pincer-complex
      catalysis. These reactions are regio- and stereoselective proceeding with high
      isolated yields. Competitive boronation experiments indicate that under the
      applied reaction conditions the allylic displacement of a hydroxy group is faster
      than the displacement of an acetate leaving group. It is assumed that the hydroxy
      group of the allyl alcohol is converted to a diboronic acid ester functionality,
      which can easily be substituted.

PMID- 16594693
TI  - Molybdenum-catalyzed asymmetric allylation of 3-alkyloxindoles: application to
      the formal total synthesis of (-)-physostigmine.
AB  - The first example of Mo-catalyzed asymmetric allylation for the generation of
      quaternary stereocenters at a prochiral nucleophile is reported. A variety of 3
      alkyl oxindoles can be alkylated with high yields and enantioselectivity. This
      method provides expedited access to (-)-physostigmine and its analogues.

PMID- 16594694
TI  - Synthesis of substituted pyridine derivatives via the ruthenium-catalyzed
      cycloisomerization of 3-azadienynes.
AB  - We describe a two-step conversion of various N-vinyl and N-aryl amides to the
      corresponding substituted pyridines and quinolines, respectively. The process
      involves the direct conversion of amides, including sensitive N-vinyl amides, to
      the corresponding trimethylsilyl alkynyl imines followed by a ruthenium-catalyzed
      protodesilylation and cycloisomerization. A wide range of new alkynyl imines are
      prepared and readily converted to the corresponding azaheterocycles.

PMID- 16594696
TI  - C-H bond activation and subsequent C-C bond formation promoted by osmium: 2
      vinylpyridine-acetylene couplings.
AB  - Complex OsH2Cl2(PiPr3)2 promotes the C-H activation of 2-vinylpyridine and
      subsequently couples the activated substrate with a second 2-vinylpyridine and
      two acetylene molecules. In the absence of 2-vinylpyridine, the activated
      substrate is coupled with an acetylene unit to afford a 2-butadienylpyridine
      derivative.

PMID- 16594695
TI  - Catalytic enantioselective O-H insertion reactions.
AB  - The first effective method for catalytic enantioselective insertions into O-H
      bonds has been developed. Specifically, a copper/bisazaferrocene catalyst couples
      alcohols such as 2-trimethylsilylethanol with alpha-aryl-alpha-diazo esters in
      high yield and good ee.

PMID- 16594697
TI  - The effect of carbonyl substitution on the strain energy of small ring compounds
      and their six-member ring reference compounds.
AB  - High level ab initio calculations have been applied to the estimation of ring
      strain energies (SE) of a series of three- and six-member ring compounds. The SE
      of cyclohexane has been estimated to be 2.2 kcal/mol at the CBS-APNO level of
      theory. The SE of cyclopropane has been increased to 28.6 kcal/mol after
      correction for the one-half of the SE of cyclohexane. The SEs of a series of
      carbonyl-containing three-member ring compounds have been estimated at the CBS-Q
      level by their combination with cyclopropane to produce a six-member ring
      reference compound. The SEs of cyclopropanone (5), the simplest alpha-lactone (6)
      [oxiranone], and alpha-lactam (7) [aziridinone] have been predicted to be 49, 47,
      and 55 kcal/mol, respectively, after correction for the SE of the corresponding
      six-member ring reference compound. The SEs of cyclohexanone, delta
      valerolactone, and delta-valerolactam have been estimated to be 4.3, 11.3, and
      5.1 kcal/mol, respectively. Marked increases in the SE of silacyclopropane and
      siladioxirane have been established, while significant decreases in the SEs of
      phosphorus, sulfur, dioxa- and diaza-containing three-member ring compounds were
      observed. The ring strain energies of the hydrocarbons (but not heterocycles)
      exhibit a strong correlation with their C-H bond dissociation energies.

PMID- 16594698
TI  - Assemblies of supramolecular porphyrin dimers in pentagonal and hexagonal arrays
      exhibiting light-harvesting antenna function.
AB  - Porphyrin-based supramolecular macrocyclic arrays were synthesized as mimics of
      photosynthetic light-harvesting (LH) antennae. Pentameric and hexameric
      macrocyclic porphyrin arrays EP5 and EP6 were constructed by complementary
      coordination of m-bis(ethynylene)phenylene-linked zinc-imidazolylporphyrin Zn-EP
      Zn. The proton NMR spectra of noncovalently linked N-EP5 and N-EP6 indicate fast
      rotation of the porphyrin moieties along the ethyne axis. These macrocycles were
      covalently linked and identified as C-EP5 (6832 Da) and C-EP6 (8199 Da) by mass
      spectrometry. Fluorescence quantum yields of C-EP2 (10.0%), C-EP5 (10.1%), and C
      EP6 (11.0%), even larger than that of the unit coordination dimer C-EP1 (9.3%),
      were significantly increased from those of the series without the ethynylene
      linkage. The order of increasing fluorescence quantum yields was parallel to that
      of decreasing fluorescence lifetimes (C-EP1 (1.65 ns), C-EP2 (1.45 ns), C-EP5
      (1.42 ns), and C-EP6 (1.38 ns)), indicating that the radiative decay rate kF
      increased relative to the other decay rates with an increase in the number of
      ring components. Based on the exciton-exciton annihilation and anisotropy
      depolarization times, the excitation energy hopping (EEH) times in these
      macrocyclic systems were obtained as 21 ps for C-EP5 and 12.8 ps for C-EP6. EEH
      times depend strongly on the orientation factor of the component transition
      dipoles in the macrocyclic arrays. The hexagonal macrocyclic array with an
      orientation of better transition dipole coupling resulted in faster EEH time
      compared to the pentagonal one.

PMID- 16594700
TI  - Unexpected H2O-induced Ar-X activation with trifluoromethylpalladium(II) aryls.
AB  - A series of new complexes [(L-L)Pd(Ar)(CF3)] (L-L = dppe, dppp, tmeda; Ar = Ph, p
      Tol, C6D5) have been synthesized and fully characterized in solution and in the
      solid state. Remarkable Ph-X activation (X = I, Cl) by [(dppe)Pd(Ph)(CF3)] (1)
      has been found to come about to cleanly produce biphenyl and [(dppe)Pd(Ph)(X)].
      This reaction does not take place under rigorously anhydrous conditions but in
      the presence of traces of water it readily occurs, exhibiting an induction period
      and being zero order in PhI. As shown by mechanistic studies, the role of water
      is to promote reduction of small quantities of the Pd(II) complex to Pd(0) which
      activates the Ph-X bond. Subsequent transmetalation to give diphenyl Pd
      complexes, followed by Ph-Ph reductive elimination give rise to the observed
      products. The water-induced reduction to catalytically active Pd(0) has been
      demonstrated to proceed via both the Pd(II)/P(III) to Pd(0)/P(V) redox mechanism
      and alpha-F transfer, followed by facile hydrolysis of the difluorocarbene to
      carbonyl, migratory insertion, and reductive elimination of PhC(X)O (X = F, OH,
      or OOCPh). In the absence of H2O and ArX, the diphosphine-stabilized
      trifluoromethyl Pd phenyl complexes undergo slow Ph-CF3 reductive elimination
      under reinforcing conditions (xylenes, 145 degrees C).

PMID- 16594699
TI  - Unprecedented alkene complex of zinc(II): structures and bonding of divinylzinc
      complexes.
AB  - This report describes the solid-state structures of a series of divinylzinc
      complexes, one of which represents the only structurally characterized zinc(II)
      pi-complex. Vinylzinc reagents, Zn[C(Me)=CH2]2 (1) and Zn[C(H)=CMe2]2 (2), have
      been synthesized and isolated as white crystalline solids in 66 and 72% yield,
      respectively. Each compound exhibits an infinite polymeric architecture in the
      solid state via a series of zinc-pi (1) and zinc-sigma-bonded (2) bridging
      interactions. Addition of chelating ligands to these divinylzinc compounds
      allowed isolation of the monomeric adducts (bipy)Zn[C(Me)=CH2]2 (1.bipy),
      (tmeda)Zn[C(Me)=CH2]2 (1*tmeda), (bipy)Zn[C(H)=CMe2]2 (2*bipy), and
      (tmeda)Zn[C(H)=CMe2]2 (2*tmeda), of which 1*bipy, 2*bipy, and 2*tmeda have been
      characterized crystallographically.

PMID- 16594701
TI  - New multicomponent approach for the creation of chiral quaternary centers in the
      carbonyl allylation reactions.
AB  - The combined regio- and stereo-controlled carbometalation reaction of alkynyl
      sulfoxide followed by a zinc homologation and finally an allylation reaction led,
      in a single-pot operation, to chiral homoallylic alcohols in excellent yields and
      diastereoselectivities for the creation of chiral quaternary and tertiary
      centers. The key features in all of the reactions that are described in this
      article are the high degree of stereocontrol, the level of predictability, and
      "the ease of execution" which ensures success in the application of such methods.
      The chiral sulfinyl moiety can be finally removed by simple treatment with
      alkyllithiums, which allows further functionalizations of the carbon skeleton. By
      using one of these methods, the creation of chiral quaternary centers with the
      smallest possible difference, namely CD3 versus CH3 and 13CH3 versus CH3, was
      easily performed.

PMID- 16594702
TI  - Density functional theory analysis of the reaction pathway for methane oxidation
      to acetic acid catalyzed by Pd2+ in sulfuric acid.
AB  - Density functional theory has been used to investigate the thermodynamics and
      activation barriers associated with the direct oxidation of methane to acetic
      acid catalyzed by Pd2+ cation in concentrated sulfuric acid. Pd2+ cations in such
      solutions are ligated by two bisulfate anions and by one or two molecules of
      sulfuric acid. Methane oxidation is initiated by the addition of CH4 across one
      of the Pd-O bonds of a bisulfate ligand to form Pd(HSO4)(CH3)(H2SO4)2. The latter
      species will react with CO to produce Pd(HSO4)(CH3CO)(H2SO4)2. The most likely
      path to the final products is found to be via oxidation of Pd(HSO4)(CH3)(H2SO4)2
      and Pd(HSO4)(CH3CO)(H2SO4)2 to form Pd(eta2-HSO4)(HSO4)2(CH3)(H2SO4) and Pd(eta2
      HSO4)(HSO4)2(CH3CO)(H2SO4), respectively. CH3HSO4 or CH3COHSO4 is then produced
      by reductive elimination from the latter two species, and CH(3)COOH is then
      formed by hydrolysis of CH3COHSO4. The loss of Pd2+ from solution to form Pd(0)
      or Pd-black is predicted to occur via reduction with CO. This process is offset,
      though, by reoxidation of palladium by either H2SO4 or O2.

PMID- 16594703
TI  - Morphology phase diagram of ultrathin anatase TiO2 films templated by a single PS
      b-PEO block copolymer.
AB  - Ultrathin TiO2 films showing rich morphologies are prepared on Si(100) substrates
      using sol-gel chemistry coupled with an amphilic polystyrene-block-poly(ethylene
      oxide) (PS-b-PEO) diblock copolymer as a structure-directing agent. The block
      copolymer undergoes a good-poor solvent pair induced phase separation in a mixed
      solution of 1,4-dioxane, concentrated hydrochloric acid (HCl), and titanium
      tetraisopropoxide (TTIP). By adjusting the weight fractions of 1,4-dioxane, HCl,
      and TTIP, inorganic block copolymer composite films containing a variety of
      different morphologies are obtained. On the basis of the results a ternary phase
      diagram of the morphologies is mapped. By calcination, anatase TiO2 films are
      achieved. The morphologies and crystallographic phase of the films are studied
      with AFM, SEM, and XRD, respectively, and the formation mechanisms of the
      different morphologies are discussed.

PMID- 16594704
TI  - Concepts in receptor optimization: targeting the RGD peptide.
AB  - Synthetic receptors have a wide range of potential applications, but it has been
      difficult to design low molecular weight receptors that bind ligands with high,
      "proteinlike" affinities. This study uses novel computational methods to
      understand why it is hard to design a high-affinity receptor and to explore the
      limits of affinity, with the bioactive peptide RGD as a model ligand. The M2
      modeling method is found to yield excellent agreement with experiment for a known
      RGD receptor and then is used to analyze a series of receptors generated in
      silico with a de novo design algorithm. Forces driving binding are found to be
      systematically opposed by proportionate repulsions due to desolvation and
      entropy. In particular, strong correlations are found between Coulombic
      attractions and the electrostatic desolvation penalty and between the mean energy
      change on binding and the cost in configurational entropy. These correlations
      help explain why it is hard to achieve high affinity. The change in surface area
      upon binding is found to correlate poorly with affinity within this series.
      Measures of receptor efficiency are formulated that summarize how effectively a
      receptor uses surface area, total energy, and Coulombic energy to achieve
      affinity. Analysis of the computed efficiencies suggests that a low molecular
      weight receptor can achieve proteinlike affinity. It is also found that
      macrocyclization of a receptor can, unexpectedly, increase the entropy cost of
      binding because the macrocyclic structure further restricts ligand motion.

PMID- 16594705
TI  - Understanding GFP posttranslational chemistry: structures of designed variants
      that achieve backbone fragmentation, hydrolysis, and decarboxylation.
AB  - The green fluorescent protein (GFP) creates a fluorophore out of three sequential
      amino acids by promoting spontaneous posttranslational modifications. Here, we
      use high-resolution crystallography to characterize GFP variants that not only
      undergo peptide backbone cyclization but additional denaturation-induced peptide
      backbone fragmentation, native peptide hydrolysis, and decarboxylation reactions.
      Our analyses indicate that architectural features that favor GFP peptide
      cyclization also drive peptide hydrolysis. These results are relevant for the
      maturation pathways of GFP homologues, such as the kindling fluorescent protein
      and the Kaede protein, which use backbone cleavage to red-shift the spectral
      properties of their chromophores. We further propose a photochemical mechanism
      for the decarboxylation reaction, supporting a role for the GFP protein
      environment in facilitating radical formation and one-electron chemistry, which
      may be important in activating oxygen for the oxidation step of chromophore
      biosynthesis. Together, our results characterize GFP posttranslational
      modification chemistry with implications for the energetic landscape of backbone
      cyclization and subsequent reactions, and for the rational design of
      predetermined spontaneous backbone cyclization and cleavage reactions.

PMID- 16594706
TI  - Tandem mass spectrometry of intact GroEL-substrate complexes reveals substrate
      specific conformational changes in the trans ring.
AB  - It has been suggested that the bacterial GroEL chaperonin accommodates only one
      substrate at any given time, due to conformational changes to both the cis and
      trans ring that are induced upon substrate binding. Using electrospray ionization
      mass spectrometry, we show that indeed GroEL binds only one molecule of the model
      substrate Rubisco. In contrast, the capsid protein of bacteriophage T4, a natural
      GroEL substrate, can occupy both rings simultaneously. As these substrates are of
      similar size, the data indicate that each substrate induces distinct
      conformational changes in the GroEL chaperonin. The distinctive binding behavior
      of Rubisco and the capsid protein was further investigated using tandem mass
      spectrometry on the intact 800-914 kDa GroEL-substrate complexes. Our data
      suggest that even in the gas phase the substrates remain bound inside the GroEL
      cavity. The analysis revealed further that binding of Rubisco to the GroEL
      oligomer stabilizes the chaperonin complex significantly, whereas binding of one
      capsid protein did not have the same effect. However, addition of a second capsid
      protein molecule to GroEL resulted in a similar stabilizing effect to that
      obtained after the binding of a single Rubisco. On the basis of the stoichiometry
      of the GroEL chaperonin-substrate complex and the dissociation behavior of the
      two different substrates, we hypothesize that the binding of a single capsid
      polypeptide does not induce significant conformational changes in the GroEL trans
      ring, and hence the unoccupied GroEL ring remains accessible for a second capsid
      molecule.

PMID- 16594707
TI  - Reductive Bergman-type cyclizations of cross-conjugated enediynes to fulvene and
      fulvalene anions: the role of the substituent.
AB  - Various cross-conjugated enediynes undergo "Bergman-type" cycloaromatizations
      upon reduction with potassium metal, generating anions of fulvenes and fulvalene
      derivatives. This new anionic cyclization is considerably more facile than the
      classic Bergman cyclization with linear enediynes, creating highly reactive
      diradicals at -78 degrees C. Not all cross-conjugated enediynes yield cyclized
      dianions upon reduction; some give uncyclized, Y-shaped, cross-conjugated
      dianions, while others apparently yield radical-anions that either dimerize or
      persist as monomers. One system yields both a cyclized and an uncyclized dianion.
      The substituents are thus shown to be a critical factor in determining the
      outcome of the reduction. Cyclization occurs within a specific "window of
      opportunity" that is governed by the substituents.

PMID- 16594708
TI  - A redox-active two-dimensional coordination polymer: preparation of silver and
      gold nanoparticles and crystal dynamics on guest removal.
AB  - A two-dimensional (2D) square-grid coordination polymer,
      {[Ni(cyclam)]2[BPTC]}n.2nH2O (1), has been assembled from [Ni(cyclam)](ClO4)2
      (cyclam = 1,4,8,11-tetraazacyclotetradecane) and H4BPTC (H4BPTC = 1,1'-biphenyl
      2,2',6,6'-tetracarboxylic acid) in H2O/MeOH (2.5:1, v/v) in the presence of
      triethylamine. When solid 1 was immersed in the EtOH solutions of AgNO3 (1.3 x
      10(-1) M) and NaAuCl4.2H2O (3.4 x 10(-2) M), respectively, for 5 min at room
      temperature, solids including Ag (3.7 +/- 0.4 nm, diameter) and Au (2 nm,
      diameter) nanoparticles were formed by the redox reactions between Ni(II) ions
      incorporated in 1 and metal ions, as evidenced by HRTEM images, EPR, and XPS
      spectra. When single-crystal 1 was heated at 180 degrees C under 10(-5) Torr for
      24 h, it was transformed to dehydrated compound {[Ni(cyclam)]2[BPTC]}n (2) in the
      single-crystal-to-single-crystal manner. The X-ray crystal structure of 2 reveals
      extensive dynamic motions of the molecular components in response to guest
      removal, involving rotation of the carboxylate and macrocycle, swing of the
      biphenyl, and bending of the macrocyclic coordination plane toward the
      carboxylate plane, which reduces the interlayer distance.

PMID- 16594709
TI  - Direct hydrogen-atom abstraction by activated bleomycin: an experimental and
      computational study.
AB  - Bleomycin (BLM), a glycopeptide antibiotic chemotherapy agent, is capable of
      single- and double-strand DNA damage. Activated bleomycin (ABLM), a low-spin
      Fe(III)-OOH complex, is the last intermediate detected prior to DNA cleavage
      following hydrogen-atom abstraction from the C-4' of a deoxyribose sugar moiety.
      The mechanism of this C-H bond cleavage reaction and the nature of the active
      oxidizing species are still open issues. We have used kinetic measurements in
      combination with density functional calculations to study the reactivity of ABLM
      and the mechanism of the initial attack on DNA. Circular dichroism spectroscopy
      was used to directly monitor the kinetics of the ABLM reaction. These experiments
      yield a deuterium isotope effect, kH/kD approximately 3 for ABLM decay,
      indicating the involvement of a hydrogen atom in the rate-determining step. H
      atom donors with relatively weak X-H bonds accelerate the reaction rate,
      establishing that ABLM is capable of hydrogen-atom abstraction. Density
      functional calculations were used to evaluate the two-dimensional potential
      energy surface for the direct hydrogen-atom abstraction reaction of the
      deoxyribose 4'-H by ABLM. The calculations confirm that ABLM is thermodynamically
      and kinetically competent for H-atom abstraction. The activation and reaction
      energies for this pathway are favored over both homolytic and heterolytic O-O
      bond cleavage. Direct H-atom abstraction by ABLM would generate a reactive
      Fe(IV)=O species, which would be capable of a second DNA strand cleavage, as
      observed in vivo. This study provides experimental and theoretical evidence for
      direct H-atom abstraction by ABLM and proposes an attractive mechanism for the
      role of ABLM in double-strand cleavage.

PMID- 16594710
TI  - Stochastic modeling of CW-ESR spectroscopy of [60]fulleropyrrolidine bisadducts
      with nitroxide probes.
AB  - In this work, we address the interpretation of continuous wave electron spin
      resonance (CW-ESR) spectra of fulleropyrrolidine bisadducts with nitroxide
      addends. Our approach is based on a definition of the spin Hamiltonian which
      includes exchange and dipolar interactions and on a complete numerical solution
      of the resulting stochastic Liouville equation, with inclusion of diffusive
      rotational dynamics. CW-ESR spectra are simulated for a series of C60 bisadducts
      made up of four trans isomers and the equatorial isomer. A nonlinear least
      squares fitting procedure allows extraction directly from the available
      experimental spectra of a wide range of parameters, namely interprobe relative
      distances, diffusion tensors, and values of the exchange parameter J. Results are
      in good agreement with previous, more phenomenological estimates, proving that
      the combination of sensitive ESR spectroscopy based on multiple spin labeling
      with nitroxide radicals and sophisticated modeling can be highly helpful in
      providing structural and dynamic information on molecular systems.

PMID- 16594711
TI  - Tuning anisotropy barriers in a family of tetrairon(III) single-molecule magnets
      with an S = 5 ground state.
AB  - Tetrairon(III) Single-Molecule Magnets (SMMs) with a propeller-like structure
      exhibit tuneable magnetic anisotropy barriers in both height and shape. The
      clusters [Fe4(L1)2(dpm)6] (1), [Fe4(L2)2(dpm)6] (2), [Fe4(L3)2(dpm)6].Et2O
      (3.Et2O), and [Fe4(OEt)3(L4)(dpm)6] (4) have been prepared by reaction of
      [Fe4(OMe)6(dpm)6] (5) with tripodal ligands R-C(CH2OH)3 (H3L1, R = Me; H3L2, R =
      CH2Br; H3L3, R = Ph; H3L4, R = tBu; Hdpm = dipivaloylmethane). The iron(III) ions
      exhibit a centered-triangular topology and are linked by six alkoxo bridges,
      which propagate antiferromagnetic interactions resulting in an S = 5 ground spin
      state. Single crystals of 4 reproducibly contain at least two geometric isomers.
      From high-frequency EPR studies, the axial zero-field splitting parameter (D) is
      invariably negative, as found in 5 (D = -0.21 cm(-1)) and amounts to -0.445 cm(
      1) in 1, -0.432 cm(-1) in 2, -0.42 cm(-1) in 3.Et2O, and -0.27 cm(-1) in 4
      (dominant isomer). The anisotropy barrier Ueff determined by AC magnetic
      susceptibility measurements is Ueff/kB = 17.0 K in 1, 16.6 K in 2, 15.6 K in
      3.Et2O, 5.95 K in 4, and 3.5 K in 5. Both |D| and U(eff) are found to increase
      with increasing helical pitch of the Fe(O2Fe)3 core. The fourth-order
      longitudinal anisotropy parameter B4(0), which affects the shape of the
      anisotropy barrier, concomitantly changes from positive in 1 ("compressed
      parabola") to negative in 5 ("stretched parabola"). With the aid of spin
      Hamiltonian calculations the observed trends have been attributed to fine
      modulation of single-ion anisotropies induced by a change of helical pitch.

PMID- 16594712
TI  - Single-site homogeneous and heterogeneized gold(III) hydrogenation catalysts:
      mechanistic implications.
AB  - Au(III)-Schiff base complexes are active hydrogenation catalysts, giving turnover
      frequencies similar to those of the corresponding complexes of Pd(II), which has
      the same d8 electronic structure as Au(III). The mechanism of the reaction has
      been studied in detail by a combination of kinetic experiments and theoretical
      calculations. It is predicted and tested that the nature of the solvent plays a
      critical role for the heterolytic cleavage of H2 (controlling step). Taking this
      into account, and by properly selecting the nature of solid supports (polarity
      and proton-donating ability), it was possible to strongly increase the activity
      of the homogeneous Au(III) and Pd(II) catalysts by grafting them onto the
      surface.

PMID- 16594713
TI  - Reaction progress of chromophore biogenesis in green fluorescent protein.
AB  - The mature form of green fluorescent protein (GFP) is generated by a spontaneous
      self-modification process that is essentially irreversible. A key step in
      chromophore biosynthesis involves slow air oxidation of an intermediate species,
      in which the backbone atoms of residues 65-67 have condensed to form a five
      membered heterocycle. We have investigated the kinetics of hydrogen peroxide
      evolution during in vitro GFP maturation and found that the H2O2 coproduct is
      generated prior to the acquisition of green fluorescence at a stoichiometry of
      1:1 (peroxide/chromophore). The experimental progress curves were computer-fitted
      to a three-step mechanism, in which the first step proceeds with a time constant
      of 1.5 (+/-1.1) min and includes protein folding and peptide cyclization. Kinetic
      data obtained by HPLC analysis support a rapid cyclization reaction that can be
      reversed upon acid denaturation. The second step proceeds with a time constant of
      34.0 (+/-1.5) min and entails rate-limiting protein oxidation, as supported by a
      mass loss of 2 Da observed for tryptic peptides derived from species that
      accumulate during the reaction. The final step in GFP maturation proceeds with a
      time constant of 10.6 (+/-1.2) min, suggesting that this step may contribute to
      overall rate retardation. We propose that under highly aerobic conditions, the
      dominant reaction path follows a cyclization-oxidation-dehydration mechanism, in
      which dehydration of the heterocycle is facilitated by slow proton abstraction
      from the Tyr66 beta-carbon. In combination, the results presented here suggest a
      role for molecular oxygen in trapping the cyclized form of GFP.

PMID- 16594714
TI  - Electron transfer from sodium to oriented nitromethane, CH3NO2: probing the
      spatial extent of unoccupied orbitals.
AB  - Beams of sodium atoms with energies of a few eV are crossed with a beam of
      oriented CH3NO2 molecules to study the effect of collision energy and orientation
      on electron transfer. The electron transfer produces Na+ ions and free electrons,
      parent negative ions (CH)NO2-), and fragmentation ions NO2- and O- in proportions
      that depend on the collision energy. The steric asymmetry is very small or zero
      and suggests that production of all of the ions is favored by sideways attack
      with respect to the permanent dipole along the C-N axis. In these experiments,
      the electron appears to be transferred into the 2B1 state of the anion comprising
      mainly the pi*NO LUMO, producing a valence-bound state rather than a dipole-bound
      state.

PMID- 16594715
TI  - Intramolecular electron transfer through the 20-position of a chlorophyll a
      derivative: an unexpectedly efficient conduit for charge transport.
AB  - Suzuki cross-coupling reactions have afforded 20-phenyl-substituted Chlorophyll a
      derivatives (ZCPh) in good yields and significant quantities from readily
      available Chl a. A series of donor-acceptor dyads was synthesized in which
      naphthalene-1,8:4,5-bis(dicarboximide) or either of two perylene-3,4:9,10
      bis(dicarboximide) electron acceptors is attached to the para position of the 20
      phenyl group. Comparisons with the analogous dyads based on a zinc 5,10,15-tri(n
      pentyl)-20-phenylporphyrin donor show that, for a given acceptor and solvent, the
      rates of photoinduced charge separation and recombination as well as the
      calculated electronic coupling matrix elements, V, for these reactions differ by
      less than a factor of 2. However, EPR and ENDOR spectroscopy corroborated by DFT
      calculations show that the highest occupied MO of ZCPh+* has little spin (charge)
      density at the 20-carbon atom, whereas Z3PnPh+* has significant spin (charge)
      density there, implying that V, and therefore the electron-transfer rates, should
      differ significantly for these two macrocyclic donors. DFT calculations on ZCPh+*
      and Z3PnPh+*, with two -0.5 charges located where the nearest carbonyl oxygen
      atoms of the acceptor would reside in the donor-acceptor dyads, show that the
      presence of the negative charges significantly shifts the charge density of both
      ZCPh+* and Z3PnPh+* from the macrocycle onto the phenyl rings. Thus, the presence
      of adjacent covalently linked radical anions at a fixed location relative to each
      of these radical cations results in nearly identical electronic coupling matrix
      elements for electron transfer and therefore very similar rates.

PMID- 16594716
TI  - Dynamics and mechanism of bridge-dependent charge separation in pyrenylurea
      nitrobenzene pi-stacked protophanes.
AB  - Herein are reported the synthesis, structure, and electronic properties of a
      series of tertiary di- and polyarylureas possessing pyrene and nitrobenzene end
      groups separated by a variable number of internal phenylenediamine bridging
      groups. These molecules adopt folded "protophane" structures in which the
      adjacent arenes are loosely pi-stacked. The behavior of both the pyrene and
      nitrobenzene singlet states has been investigated by means of femtosecond
      broadband pump-probe spectroscopy, and the transients have been assigned on the
      basis of comparison to reference molecules. Femtosecond time resolution permits
      direct observation of the fast internal conversion process for both the pyrene
      and nitrobenzene upper singlet states, as well as the intersystem crossing of
      nitrobenzene. The ultrafast (ca. 100 fs) charge separation of the donor-acceptor
      urea having no bridging group is attributed to an internal conversion process.
      The slower charge separation and charge recombination of the donor-acceptor urea
      having a single bridging group occur via a bridge-mediated superexchange process.
      Addition of a second bridging unit results in a role reversal for the pyrene
      singlet state, which now serves as an excited-state acceptor with the bridging
      units serving as the electron donors. The change in the directionality of
      electron transfer upon addition of a second bridging phenylenediamine is a
      consequence of a decrease in the bridge oxidation potential as well as a decrease
      in the rate constant for single-step superexchange electron transfer.

PMID- 16594717
TI  - Vibrational spectroscopy of mass-selected [UO2(ligand)n]2+ complexes in the gas
      phase: comparison with theory.
AB  - The gas-phase infrared spectra of discrete uranyl ([UO2]2+) complexes ligated
      with acetone and/or acetonitrile were used to evaluate systematic trends of
      ligation on the position of the O=U=O stretch and to enable rigorous comparison
      with the results of computational studies. Ionic uranyl complexes isolated in a
      Fourier transform ion cyclotron resonance mass spectrometer were fragmented via
      infrared multiphoton dissociation using a free electron laser scanned over the
      mid-IR wavelengths. The asymmetric O=U=O stretching frequency was measured at
      1017 cm(-1) for [UO2(CH3COCH3)2]2+ and was systematically red shifted to 1000 and
      988 cm(-1) by the addition of a third and fourth acetone ligand, respectively,
      which was consistent with increased donation of electron density to the uranium
      center in complexes with higher coordination number. The values generated
      computationally using LDA, B3LYP, and ZORA-PW91 were in good agreement with
      experimental measurements. In contrast to the uranyl frequency shifts, the
      carbonyl frequencies of the acetone ligands were progressively blue shifted as
      the number of ligands increased from two to four and approached that of free
      acetone. This observation was consistent with the formation of weaker noncovalent
      bonds between uranium and the carbonyl oxygen as the extent of ligation
      increases. Similar trends were observed for [UO2(CH3CN)n]2+ complexes, although
      the uranyl asymmetric stretching frequencies were greater than those measured for
      acetone complexes having equivalent coordination, which is consistent with the
      fact that acetonitrile is a weaker nucleophile than is acetone. This conclusion
      was confirmed by the uranyl stretching frequencies measured for mixed
      acetone/acetonitrile complexes, which showed that substitution of one acetone for
      one acetonitrile produced a modest red shift of 3-6 cm(-1).

PMID- 16594718
TI  - Probing lipid vesicles by bimolecular association and dissociation trajectories
      of single molecules.
AB  - Vesicles prepared by DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) and SOPC
      (1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine) lipid molecules having sizes
      smaller than the diffraction-limited focused laser beam have been used to confine
      single molecules in the laser focus. The confinement of single molecules in a
      volume smaller than the focused laser beam leads to a Gaussian distribution of
      single molecule fluorescence intensity. The interactions of single Nile Red
      molecules with DMPC and SOPC lipid bilayers were studied by single molecule
      fluorescence confocal microscopy. Nile Red molecules were observed to associate
      with and dissociate from individual DMPC and SOPC vesicles adsorbed on a glass
      surface, generating on-and-off fluctuations in a fluorescence signal representing
      a very low noise two-state trajectory. Off-time statistics were used to
      investigate the mean radius of the vesicles and the size distribution functions.
      The means of the on-time distributions of Nile Red in DMPC and SOPC vesicles were
      significantly different. The association and dissociation reactions of single
      Nile Red molecules with a vesicle have been studied. Features of the bimolecular
      interaction between the probe Nile Red and the vesicle were evaluated from the
      uncorrelated mean on-time and vesicle radius distributions, and the linear Nile
      Red concentration dependence of the mean off-time. Nile Red is shown to be a
      useful probe of the structural fluctuations and heterogeneity of these membrane
      structures, and it is a useful model with which to directly study a diffusion
      influenced reversible bimolecular reaction.

PMID- 16594719
TI  - Synthesis of neoglycopolymers by a combination of "click chemistry" and living
      radical polymerization.
AB  - The synthesis of novel well-defined alkyne side chain functional polymers
      featuring narrow molecular weight distributions (PDI = 1.09-1.17) by living
      radical polymerization is described. Grafting of protected and unprotected
      carbohydrates is achieved via either a C-6 or an anomeric azide (alpha or beta)
      onto these polymers by Cu(I)-catalyzed "click chemistry", providing a simple and
      efficient route to synthetic glycopolymers. The strategy provides an extremely
      powerful tool for the synthesis of libraries of materials that differ only in the
      nature of the sugar moiety presented on a well-defined polymer scaffold. A
      library of multivalent ligands were then prepared following a "coclicking"
      synthetic protocol, and the reactivity of these glycopolymers in the presence of
      concanavalin A and Ricinus communis agglutinin, model lectins able to selectively
      bind appropriate mannose and galactose derivatives, respectively, was assessed.

PMID- 16594720
TI  - Molecular tweezer and clip in aqueous solution: unexpected self-assembly,
      powerful host-guest complex formation, quantum chemical 1H NMR shift calculation.
AB  - The newly prepared water-soluble naphthalene tweezer 2a and anthracene clip 4a
      (substituted both with lithium methanephosphonate groups in the central spacer
      unit) undergo an unexpected self-assembly in aqueous solution. The highly ordered
      intertwined structures of the self-assembled dimers [2a]2 and [4a]2 were
      elucidated by quantum chemical 1H NMR shift calculations. 2a and 4a form
      extremely stable host-guest complexes with N-methylnicotinamide 8 in methanol and
      water as well. According to the thermodynamic parameters determined by 1H NMR
      titration experiments at various temperatures the self-assembly of 2a and 4a and
      their strong binding to NMNA 8 observed in aqueous solution are enthalpy driven
      (DeltaH << 0); the enthalpic driving force is partially compensated by an
      unfavorable entropy (TDeltaS < 0). Self-assembly and the host-guest binding are
      therefore beautiful examples of the nonclassical hydrophobic effect.

PMID- 16594721
TI  - [Fe(bpym)(CN)4]-: a new building block for designing single-chain magnets.
AB  - We herein present the preparation, crystal structure, magnetic properties, and
      theoretical study of new heterobimetallic chains of formula
      {[Fe(III)(bpym)(CN4)]2M(II)(H2O)2}.6H2O [bpym = 2,2'-bipyrimidine; M = Zn (2), Co
      (3), Cu (4), and Mn (5)] which are obtained by using the building block
      PPh4[Fe(bpym)(CN)4].H2O (1) (PPh4+= tetraphenylphosphonium) as a ligand toward
      the fully solvated MII ions. The structure of complex 1 contains mononuclear
      [Fe(bpym)(CN)4]- anions. Compounds 2-5 are isostructural 4,2-ribbonlike
      bimetallic chains where the [Fe(bpym)(CN)4]- unit acts as a bis-monodenate ligand
      through two of its four cyanide ligands toward the M atom. Water hexamer clusters
      (4) and regular alternating fused six- and four-membered water rings with two
      dangling water molecules (2, 3, and 5) are trapped between the cyanide-bridged
      4,2-ribbonlike chains. 1 and 2 behave as magnetically isolated low-spin iron(III)
      centers. 3 behaves as a single-chain magnet (SCM) with intrachain ferromagnetic
      coupling, slow magnetic relaxation, hysteresis effects, and frequency-dependent
      ac signals at T < 7 K). As expected for a thermally activated process, the
      nucleation field (Hn) in 3 increases with decreasing T and increasing v. Below
      1.0 K, Hn becomes temperature independent but remains strongly sweep rate
      dependent. In this temperature range, the reversal of the magnetization may be
      induced by a quantum nucleation of a domain wall that then propagates due to the
      applied field. 4 and 5 are ferro- and ferrimagnetic chains respectively, with
      metamagnetic-like behavior (4). DFT-type calculations and QMC methodology
      provided a good understanding of the magnetic properties of 3-5.

PMID- 16594722
TI  - Surface-rolling molecules.
AB  - Design, syntheses, and testing of new, fullerene-wheeled single molecular
      nanomachines, namely, nanocars and nanotrucks, are presented. These nanovehicles
      are composed of three basic components that include spherical fullerene wheels,
      freely rotating alkynyl axles, and a molecular chassis. The use of spherical
      wheels based on C60 and freely rotating axles based on alkynes permits directed
      nanoscale rolling of the molecular structure on gold surfaces. The rolling motion
      observed by STM resembles the same motion performed by macroscopic entities in
      which rolling occurs perpendicular to the axles. A new synthesis methodology, in
      situ ethynylation of fullerenes, was developed for the realization of the
      fullerene-wheeled molecular machines. Four generations of the fullerene-wheeled
      structures were developed, and the latest fourth generation nanocar, 3b, along
      with three-wheeled triangular compounds, 4a and 4b, provided definitive evidence
      for fullerene-based wheel-like rolling motion, not stick-slip or sliding
      translation. The studies here underscore the ability to control directionality of
      motion in molecular-sized nanostructures through precise molecular design and
      synthesis.

PMID- 16594723
TI  - A molecular full-adder and full-subtractor, an additional step toward a
      moleculator.
AB  - Over the past decade, there has been remarkable progress in the development of
      molecular logic and arithmetic systems, which has brought chemists closer to the
      realization of a molecular scale calculator (a Moleculator). This paper describes
      a significant step in this direction. By integrating past and new approaches for
      molecular logic reconfiguration, we were able to load advanced arithmetic
      calculations onto a single molecular species. Exchanging chemical inputs,
      monitoring at several wavelengths simultaneously, as well as using negative logic
      for the transmittance mode significantly increase the input and output
      information channels of the processing molecule. Changing the initial state of
      the processor is an additional approach used for altering the logical output of
      the device. Finally, introducing degeneracy to the chemical inputs or,
      alternatively, controlling their interactions to form identical chemical states
      minimizes the complexity of realizing three-bits addition and subtraction at the
      molecular scale. Consequently, using a commercially available fluorescein
      molecule, acid and base chemical inputs, and a simple UV-vis measurement setup,
      integration of a full-adder and, for the first time, a full-subtractor is now
      possible within individual molecules.

PMID- 16594724
TI  - Synthesis, anion exchange, and delamination of Co-Al layered double hydroxide:
      assembly of the exfoliated nanosheet/polyanion composite films and magneto
      optical studies.
AB  - This paper describes a systematic study on the synthesis, anion exchange, and
      delamination of Co-Al layered double hydroxide (LDH), with the aim of achieving
      fabrication and clarifying the properties of LDH nanosheet/polyanion composite
      films. Co-Al-CO3 LDH hexagonal platelets of 4 mum in lateral size were
      synthesized by the urea method under optimized reaction conditions. The as
      prepared CO3(2-)-LDH was converted to Cl- -LDH by treating with a NaCl-HCl mixed
      solution, retaining its high crystallinity and hexagonal platelike morphology.
      LDHs intercalated with a variety of anions (such as NO3-, ClO4-, acetate,
      lactate, dodecyl sulfate, and oleate) were further prepared from Cl- -LDH via an
      anion-exchange process employing corresponding salts. Exchanged products in
      various anion forms were found to show different delamination behaviors in
      formamide. Among them, best results were observed for NO3- -LDH in terms of the
      exfoliating degree and the quality of the exfoliated nanosheets. The delamination
      gave a pink transparent suspension containing well-defined nanosheets with
      lateral sizes of up to 2 microm. The resulting nanosheets were assembled layer-by
      layer with an anionic polymer, poly(sodium styrene 4-sulfonate) (PSS), onto
      quartz glass substrates to produce composite films. Magnetic circular dichroism
      (MCD) measurements revealed that the assembled multilayer films exhibited an
      interesting magneto-optical response.

PMID- 16594725
TI  - Benzonitrile extrusion from molybdenum(IV) ketimide complexes obtained via
      radical C-E (E = O, S, Se) bond formation: toward a new nitrogen atom transfer
      reaction.
AB  - Beta-elimination is explored as a possible means of nitrogen-atom transfer into
      organic molecules. Molybdenum(IV) ketimide complexes of formula (Ar[t
      Bu]N)3Mo(N=C(X)Ph), where Ar = 3,5-Me2C6H3 and X = SC6F5, SeC6F5, or O2CPh, are
      formally derived from addition of the carbene fragment [:C(X)Ph] to the terminal
      nitrido molybdenum(VI) complex (Ar[t-Bu]N)3Mo identical with N in which the
      nitrido nitrogen atom is installed by scission of molecular nitrogen. Herein the
      pivotal (Ar[t-Bu]N)3Mo(N=C(X)Ph) complexes are obtained through independent
      synthesis, and their propensity to undergo beta-X elimination, i.e., conversion
      to (Ar[t-Bu]N)3MoX + PhC identical with N, is investigated. Radical C-X bond
      formation reactions ensue when benzonitrile is complexed to the three-coordinate
      molybdenum(III) complex (Ar[t-Bu]N)3Mo and then treated with 0.5 equiv of X2,
      leading to facile assembly of the key (Ar[t-Bu]N)3Mo(N=C(X)Ph) molecules. Treated
      herein are synthetic, structural, thermochemical, and kinetic aspects of (i) the
      radical C-X bond formation and (ii) the ensuing beta-X elimination processes.
      Beta-X elimination is found to be especially facile for X = O2CPh, and the
      reaction represents an attractive component of an overall synthetic cycle for
      incorporation of dinitrogen-derived nitrogen atoms into organic nitrile (R-C
      identical with N) molecules.

PMID- 16594726
TI  - Nanostructuration of phenylenevinylenediimide-bridged silsesquioxane: from
      electroluminescent molecular J-aggregates to photoresponsive polymeric H
      aggregates.
AB  - A new approach to control molecular aggregation of pi-conjugated chromophores in
      the solid state has been investigated. Our strategy was to use a modifiable bulky
      fragment which should induce a J-aggregation and offer the possibility to reach
      an H-aggregation upon its chemical modification by lateral slip of pi-conjugated
      molecules. The chosen fragment for that purpose was the hydrolyzable
      triethoxysilane function (Si(OEt)3). Our objective was to design and synthesize
      electroluminescent or solar cell hybrid organic-inorganic materials by the sol
      gel process applied to a bifunctionalized silane. With this intention, the
      synthesis of the sol-gel processable phenylenevinylenediimide silsesquioxane 6
      was accomplished and the study of spin-coated thin films of the pure silane
      precursor subjected or not to the sol-gel process has been carried out. Optical
      properties of 6 are consistent with the formation of J-aggregates in the solid
      state due to the steric hindrance introduced by the triethoxysilane units.
      Conversely, the spectroscopic behavior observed for the hybrid film 6F is
      attributed to an H-aggregation corresponding to a "card pack" orientation of the
      distyrylbenzeneimide chromophores in the compressed silicate network. Morevover,
      6 and 6F also exhibited different electronic behaviors: light-emitting diodes
      exhibited high brightness with the native precursor 6 and almost no light output
      with the sol-gel processed silsesquioxane 6F. Photovoltaic cells showed the
      opposite behavior with low photocurrent generation in the precursor case and
      higher photocurrents with the sol-gel processed layers. These results provide a
      deeper understanding of the present self-assembly process that is strongly
      governed by the molecular packing of the oligosiloxane precursor.

PMID- 16594727
TI  - Internal water molecules and magnetic relaxation in agarose gels.
AB  - Agarose gels have long been known to produce exceptionally large enhancements of
      the water 1H and 2H magnetic relaxation rates. The molecular basis for this
      effect has not been clearly established, despite its potential importance for a
      wide range of applications of agarose gels, including their use as biological
      tissue models in magnetic resonance imaging. To resolve this issue, we have
      measured the 2H magnetic relaxation dispersion profile from agarose gels over
      more than 4 frequency decades. We find a very large dispersion, which, at neutral
      pH, is produced entirely by internal water molecules, exchanging with bulk water
      on the time scale 10(-8)-10(-6) s. The most long-lived of these dominate the
      dispersion and give rise to a temperature maximum in the low-frequency relaxation
      rate. At acidic pH, there is also a low-frequency contribution from hydroxyl
      deuterons exchanging on a time scale of 10(-4) s. Our analysis of the dispersion
      profiles is based on a nonperturbative relaxation theory that remains valid
      outside the conventional motional-narrowing regime. The results of this analysis
      suggest that the internal water molecules responsible for the dispersion are
      located in the central cavity of the agarose double helix, as previously proposed
      on the basis of fiber diffraction data. The magnetic relaxation mechanism invoked
      here, where spin relaxation is induced directly by molecular exchange, also
      provides a molecular basis for understanding the water 1H relaxation behavior
      that governs the intrinsic magnetic resonance image contrast in biological
      tissue.

PMID- 16594728
TI  - Synthesis and photovoltaic properties of two-dimensional conjugated
      polythiophenes with bi(thienylenevinylene) side chains.
AB  - Three two-dimensional (2-D) conjugated polythiophenes with bi(thienylenevinylene)
      side chains (biTV-PTs), P1, P2, and P3, were designed and synthesized for
      application in polymer solar cells. The absorption spectral, electrochemical, and
      photovoltaic properties of the biTV-PTs were investigated and compared with those
      of poly(3-hexylthiophene) (P3HT). The biTV-PTs show a broad absorption band from
      350 to 650 nm; especially, the absorption spectrum of P3 displays a broad plateau
      and much stronger absorbance than that of P3HT in the wavelength range from 350
      to 480 nm. Cyclic voltammograms reveal that the onset oxidation and reduction
      potentials of the biTV-PTs positively shifted by ca. 0.2 V in comparison with
      those of P3HT, indicating that the HOMO energy level of the biTV-PTs is ca. 0.2
      eV lower than that of P3HT. Polymer solar cells (PSCs) were fabricated based on
      the blend of the polymers and 1-(3-methoxycarbonyl)propyl-1-phenyl-[6,6]-C-61
      (PCBM) with a weight ratio of 1:1. The open circuit voltage of the PSCs based on
      the biTV-PTs is ca. 0.1 V higher than that of P3HT, which is benefited from the
      lower HOMO levels of the biTV-PTs. The maximum power conversion efficiency (PCE)
      of the PSCs based on P3 reached 3.18% under AM 1.5, 100 mW/cm2, which is 38%
      increased in comparison with that (2.41%) of the devices based on P3HT under the
      same experimental conditions. The results indicate that the 2-D conjugated biTV
      PTs are promising polymer photovoltaic materials.

PMID- 16594730
TI  - Structure-guided recombination creates an artificial family of cytochromes P450.
AB  - Creating artificial protein families affords new opportunities to explore the
      determinants of structure and biological function free from many of the
      constraints of natural selection. We have created an artificial family comprising
      3,000 P450 heme proteins that correctly fold and incorporate a heme cofactor by
      recombining three cytochromes P450 at seven crossover locations chosen to
      minimize structural disruption. Members of this protein family differ from any
      known sequence at an average of 72 and by as many as 109 amino acids. Most (>73%)
      of the properly folded chimeric P450 heme proteins are catalytically active
      peroxygenases; some are more thermostable than the parent proteins. A multiple
      sequence alignment of 955 chimeras, including both folded and not, is a valuable
      resource for sequence-structure-function studies. Logistic regression analysis of
      the multiple sequence alignment identifies key structural contributions to
      cytochrome P450 heme incorporation and peroxygenase activity and suggests
      possible structural differences between parents CYP102A1 and CYP102A2.

PMID- 16594731
TI  - Notch promotes neural lineage entry by pluripotent embryonic stem cells.
AB  - A central challenge in embryonic stem (ES) cell biology is to understand how to
      impose direction on primary lineage commitment. In basal culture conditions, the
      majority of ES cells convert asynchronously into neural cells. However, many
      cells resist differentiation and others adopt nonneural fates. Mosaic activation
      of the neural reporter Sox-green fluorescent protein suggests regulation by cell
      cell interactions. We detected expression of Notch receptors and ligands in mouse
      ES cells and investigated the role of this pathway. Genetic manipulation to
      activate Notch constitutively does not alter the stem cell phenotype. However,
      upon withdrawal of self-renewal stimuli, differentiation is directed rapidly and
      exclusively into the neural lineage. Conversely, pharmacological or genetic
      interference with Notch signalling suppresses the neural fate choice. Notch
      promotion of neural commitment requires parallel signalling through the
      fibroblast growth factor receptor. Stromal cells expressing Notch ligand
      stimulate neural specification of human ES cells, indicating that this is a
      conserved pathway in pluripotent stem cells. These findings define an unexpected
      and decisive role for Notch in ES cell fate determination. Limiting activation of
      endogenous Notch results in heterogeneous lineage commitment. Manipulation of
      Notch signalling is therefore likely to be a key factor in taking command of ES
      cell lineage choice.

PMID- 16594733
TI  - Invasive disease and toxic shock due to zoonotic Streptococcus suis: an emerging
      infection in the East?

PMID- 16594734
TI  - The elusive origin of chordoid glioma.

PMID- 16594732
TI  - Functional imaging of numerical processing in adults and 4-y-old children.
AB  - Adult humans, infants, pre-school children, and non-human animals appear to share
      a system of approximate numerical processing for non-symbolic stimuli such as
      arrays of dots or sequences of tones. Behavioral studies of adult humans
      implicate a link between these non-symbolic numerical abilities and symbolic
      numerical processing (e.g., similar distance effects in accuracy and reaction
      time for arrays of dots and Arabic numerals). However, neuroimaging studies have
      remained inconclusive on the neural basis of this link. The intraparietal sulcus
      (IPS) is known to respond selectively to symbolic numerical stimuli such as
      Arabic numerals. Recent studies, however, have arrived at conflicting conclusions
      regarding the role of the IPS in processing non-symbolic, numerosity arrays in
      adulthood, and very little is known about the brain basis of numerical processing
      early in development. Addressing the question of whether there is an early
      developing neural basis for abstract numerical processing is essential for
      understanding the cognitive origins of our uniquely human capacity for math and
      science. Using functional magnetic resonance imaging (fMRI) at 4-Tesla and an
      event-related fMRI adaptation paradigm, we found that adults showed a greater IPS
      response to visual arrays that deviated from standard stimuli in their number of
      elements, than to stimuli that deviated in local element shape. These results
      support previous claims that there is a neurophysiological link between non
      symbolic and symbolic numerical processing in adulthood. In parallel, we tested 4
      y-old children with the same fMRI adaptation paradigm as adults to determine
      whether the neural locus of non-symbolic numerical activity in adults shows
      continuity in function over development. We found that the IPS responded to
      numerical deviants similarly in 4-y-old children and adults. To our knowledge,
      this is the first evidence that the neural locus of adult numerical cognition
      takes form early in development, prior to sophisticated symbolic numerical
      experience. More broadly, this is also, to our knowledge, the first cognitive
      fMRI study to test healthy children as young as 4 y, providing new insights into
      the neurophysiology of human cognitive development.

PMID- 16594736
TI  - Asthma: pathology and pathophysiology.
AB  - CONTEXT: Asthma has been defined as a chronic inflammatory disorder of the
      airways that is associated with recruitment of inflammatory cells and the
      clinical development of wheezing, shortness of breath, chest tightness, and
      cough. Asthma is a major public health issue. It affects 5% of the United States
      population and accounts for 2 million emergency department visits, 470,000
      hospitalizations, and 4500 deaths annually. OBJECTIVE: To review the
      pathophysiology and characteristic pathologic patterns of this disease and
      discuss the possible mechanisms of production of the lesions. DATA SOURCES: We
      searched the literature using MEDLINE and OVID. We also searched related
      conference abstracts and bibliographies of selected studies. CONCLUSIONS: There
      has been a significant evolution in our understanding of asthma. Specific
      pathways and mechanisms in recent years have been studied; however, numerous
      mediators and cell receptors have raised new questions that remain to be
      answered.

PMID- 16594735
TI  - Interactions between leukotriene C4 and interleukin 13 signaling pathways in a
      mouse model of airway disease.
AB  - CONTEXT: During an asthmatic episode, leukotriene C4 (LTC4) and interleukin 13
      (IL-13) are released into the airways and are thought to be central mediators of
      the asthmatic response. However, little is known about how these molecules
      interact or affect each other's signaling pathway. OBJECTIVE: To determine if the
      LTC4 and IL-13 signaling pathways interact with each other's pathways. DESIGN: We
      examined airway responsiveness, cysteinyl LTs (Cys-LTs), and Cys-LT and IL-13
      receptor transcript levels in wild-type mice and in mice that were deficient in
      gamma-glutamyl leukotrienase (an enzyme that converts LTC4 to LTD4), STAT6
      (signal transducer and activator of transcription 6 [a critical molecule in IL-13
      signaling]), and IL-4Ralpha (a subunit of the IL-13 receptor). RESULTS: Wild-type
      (C57BL/129SvEv) and gamma-glutamyl leukotrienase-deficient mice showed increased
      airway responsiveness after intranasal instillation of IL-13; similar results
      were observed after intranasal instillation of IL-13 or LTC4 in a second wild
      type strain (BALB/c). Interleukin 13 treatment reduced levels of Cys-LTs in
      bronchoalveolar lavage fluid. This change was unaccompanied by changes in other
      arachidonic acid metabolites or in RNA transcript levels of enzymes associated
      with Cys-LT synthesis. Interleukin 13 treatment also increased transcript levels
      of the Cys-LT 1 and Cys-LT 2 receptors, while LTC4 increased transcript levels of
      the alpha1 chain of the IL-13 receptor. Furthermore, IL-4Ralpha-deficient mice
      had increased airway responsiveness to LTC4 but not to IL-13, whereas STAT6
      deficient mice failed to respond to either agonist. CONCLUSIONS: These findings
      indicate that LTC4 and IL-13 are dependent on or signal through STAT6 to increase
      airway responsiveness and that both agonists regulate expression of each other's
      receptors.

PMID- 16594737
TI  - Fine-needle aspiration of papillary thyroid carcinoma: distinguishing between
      cases that performed well and those that performed poorly in the College of
      American Pathologists Nongynecologic Cytology Program.
AB  - CONTEXT: Although the cytologic features of papillary thyroid carcinoma in fine
      needle aspiration specimens are well known, the correlation of these features
      with the ability of cytologists to identify this tumor has not been well studied.
      OBJECTIVE: To compare the cytologic features of cases of papillary thyroid
      carcinoma that performed poorly with those of cases that performed well. DESIGN:
      The cytologic features of 13 cases of papillary thyroid carcinoma from the
      College of American Pathologists Nongynecologic Cytology Program that performed
      poorly were compared with those of 15 cases that performed well. RESULTS:
      Compared with cases that performed well, cases that performed poorly were
      significantly more likely to lack marked nuclear enlargement (38% vs 100%, P <
      .001), lack pale chromatin (8% vs 47%, P = .04), and lack intranuclear inclusions
      (8% vs 53%, P = .02). The differences between the 2 groups in staining, type of
      preparation, nuclear grooves, nuclear crowding, colloid, cellularity, nuclear
      pleomorphism, and Hurthle cell change were not significant. CONCLUSIONS: Cases of
      papillary thyroid carcinoma that lack marked nuclear enlargement, pale chromatin,
      and intranuclear inclusions are significantly more difficult to recognize than
      cases that have these features. Increased awareness of these types of cases might
      improve the performance of thyroid fine-needle aspiration in clinical practice.

PMID- 16594738
TI  - Papanicolaou tests with mixed high-grade and low-grade squamous intraepithelial
      lesion features: distinct performance in the College of American Pathologists
      Interlaboratory Comparison Program in Cervicovaginal Cytopathology.
AB  - CONTEXT: Previous studies have shown that in gynecologic cytology, cases of low
      grade squamous intraepithelial lesion (LSIL) and high-grade squamous
      intraepithelial lesion (HSIL) perform differently on interpretive review. The
      performance of cases with mixed LSIL and HSIL features is unknown. OBJECTIVE: To
      compare the performance of gynecologic cytology cases of "pure" LSIL and HSIL
      with cases showing mixed LSIL and HSIL features. DESIGN: We compiled performance
      data from the College of American Pathologists Interlaboratory Comparison Program
      in Cervicovaginal Cytopathology from the years 2003 and 2004, and compared the
      performance of slides showing relatively pure LSIL and HSIL (< or = 10%
      misclassification as HSIL and LSIL, respectively) with slides showing mixed LSIL
      or HSIL features (cases misclassified as LSIL or HSIL > 10% of the time).
      RESULTS: Interpretations from a total of 4508 cases (2452 HSIL and 2056 LSIL)
      were analyzed. Overall, the sensitivity of participants on slides with a
      reference diagnosis of HSIL was 97.3%, and of LSIL was 95.9%. Performance trends
      for pure versus mixed cases varied by slide type and reference diagnosis. For
      conventional slides, participant sensitivity on pure HSIL cases was greatest
      (98.0%) and on pure LSIL cases was least (95.2%), while participant performance
      on cases with mixed features was intermediate (97.0% for mixed HSIL and 96.7% for
      mixed LSIL). In contrast, participant performance on ThinPrep slides showed the
      greatest sensitivity for mixed LSIL slides (97.9%), while performance on mixed
      HSIL slides showed the lowest sensitivity (95.7%); slides with pure features had
      intermediate sensitivity levels (96.3% for both HSIL and LSIL). Further
      evaluation demonstrated that conventional pure HSIL slides performed
      significantly better than mixed HSIL slides (P = .006), whereas mixed LSIL slides
      performed better than pure LSIL slides (P = .01). For ThinPrep slides, pure HSIL
      cases performed similarly to mixed HSIL cases (P = .43), while mixed LSIL cases
      performed better than pure LSIL cases (P = .04). CONCLUSION: Slides with mixed
      LSIL and HSIL features have measurably distinct performance characteristics in
      comparison to slides with pure LSIL or HSIL features. Participant performance on
      conventional mixed cases is distinctly different from performance on ThinPrep
      mixed cases.

PMID- 16594739
TI  - Origin of chordoid glioma of the third ventricle.
AB  - CONTEXT: Chordoid glioma is a relatively recently described unique glial neoplasm
      that has been formally codified by the World Health Organization in Pathology and
      Genetics of Tumours of the Nervous System, in which it is included along with
      astroblastoma and gliomatosis cerebri under the rubric "Tumors of Uncertain
      Origin." Many examples of chordoid glioma come to clinical attention only at a
      relatively large size and occupy a large portion of the third ventricle.
      Accordingly, the anatomic origin of chordoid glioma has been unclear and debated.
      OBJECTIVE: To examine the regional anatomic origin of chordoid glioma. DATA
      SOURCES: The clinical, imaging, histologic, immunophenotypic, and ultrastructural
      data in previously published case series and individual case reports of chordoid
      glioma were reviewed in conjunction with the study of a new case of chordoid
      glioma that presented at a relatively small size, thereby facilitating
      neuroanatomic localization. CONCLUSIONS: Chordoid glioma exhibits features of
      specialized ependymal differentiation on ultrastructural examination, and all
      examples reported in the literature to date have displayed a highly stereotypical
      suprasellar anatomic localization and an ovoid shape, as seen on neuroimaging
      studies and gross anatomy. Neuroanatomic, radiologic, and clinical evidence
      supports an anatomic origin for chordoid glioma from the vicinity of the lamina
      terminalis.

PMID- 16594740
TI  - Molecular classification of human cancers using a 92-gene real-time quantitative
      polymerase chain reaction assay.
AB  - CONTEXT: Correct diagnosis of the tissue origin of a metastatic cancer is the
      first step in disease management, but it is frequently difficult using standard
      pathologic methods. Microarray-based gene expression profiling has shown great
      promise as a new tool to address this challenge. OBJECTIVE: Adoption of
      microarray technologies in the clinic remains limited. We aimed to bridge this
      technological gap by developing a real-time quantitative polymerase chain
      reaction (RT-PCR) assay. DESIGN: We constructed a microarray database of 466
      frozen and 112 formalin-fixed, paraffin-embedded (FFPE) samples of both primary
      and metastatic tumors, measuring expression of 22,000 genes. From the microarray
      database, we used a genetic algorithm to search for gene combinations optimal for
      multitumor classification. A 92-gene RT-PCR assay was then designed and used to
      generate a database for 481 frozen and 119 FFPE tumor samples. RESULTS: The
      microarray-based K-nearest neighbor classifier demonstrated 84% accuracy in
      classifying 39 tumor types via cross-validation and 82% accuracy in predicting
      112 independent FFPE samples. We successfully translated the microarray database
      to the RT-PCR platform, which allowed an overall success rate of 87% in
      classifying 32 different tumor classes in the validation set of 119 FFPE tumor
      samples. CONCLUSIONS: The RT-PCR-based expression assay involving 92 genes
      represents a powerful tool for accurately and objectively identifying the site of
      origin for metastatic tumors, especially in the cases of cancer of unknown
      primary. The assay uses RT-PCR and routine FFPE samples, making it suitable for
      rapid clinical adoption.

PMID- 16594741
TI  - Adequacy of physician documentation of red blood cell transfusion and correlation
      with assessment of transfusion appropriateness.
AB  - CONTEXT: A major function of the hospital transfusion service is to assess the
      appropriateness of blood transfusion. Inadequate documentation of transfusions
      may hamper this assessment process. OBJECTIVE: To correlate the level of
      physician documentation of transfusion with the ability to justify transfusion.
      DESIGN: Retrospective review of red blood cell transfusions in adult patients in
      2 hospital facilities during 1-week audit periods of each month from April 2001
      to March 2003. Assessment forms were used to classify the level of physician
      documentation of transfusions into 3 groups: adequately, intermediately, and
      inadequately documented. Transfusions were deemed justified or not via comparison
      with hospital transfusion guidelines. RESULTS: There were 5062 audited red blood
      cells transfused to 2044 adult (> or = 18 years) patients. Medical records from
      154 patients transfused with 257 units of red blood cells during 172 transfusion
      events were reviewed after initial screenings of hemoglobin/hematocrit values
      failed to justify the transfusions. Nine percent of adequately documented, 50% of
      intermediately documented, and 73% of inadequately documented transfusion events
      could not be justified. Transfusion events with suboptimal (intermediate and
      inadequate) documentation accounted for 49% of all medical record-reviewed
      transfusion events and 62% could not be justified. The correlation between
      inadequate documentation and failure to justify transfusion was significant (P <
      .001), as was the correlation between suboptimal documentation and failure to
      justify transfusion (P = .03). CONCLUSIONS: There is a significant correlation
      between suboptimal documentation and failure to justify transfusions. Educating
      clinicians to improve documentation along with appropriate indications for
      transfusions may enhance efficiency of blood utilization assessment and lead to
      reduced rates of unjustifiable transfusions.

PMID- 16594742
TI  - Normal and neoplastic cells of brown adipose tissue express the adhesion molecule
      CD31.
AB  - CONTEXT: CD31 (platelet-endothelial cell adhesion molecule-1; PECAM-1), an
      adhesion molecule involved in the process of angiogenesis, is used as a marker of
      normal and neoplastic vascularization. During the assessment of angiogenesis and
      vascular invasion in a thymic carcinoid tumor, we observed unexpected
      immunostaining for CD31 in perithymic brown fat nests. OBJECTIVE: To determine
      whether CD31 is expressed by normal and neoplastic cells of brown fat, a tissue
      whose thermogenetic activity depends heavily on high perfusion. DESIGN: Formalin
      fixed, paraffin-embedded archival tissues were immunostained by the labeled
      avidin-biotin method using antibodies against CD31 (clones JC70A and 1A10) after
      retrieval of heat-induced epitopes. Archival tissues included perithymic,
      periadrenal, axillary, and neck adipose tissue in which were embedded nests of
      brown fat (n = 15), hibernoma (n = 3), lipoma (n = 6), well-differentiated
      liposarcoma (n = 4), and myxoid liposarcoma (n = 4). RESULTS: Invariably,
      multivacuolated and univacuolated adipocytes of normal brown fat and hibernomas
      were intensely positive for the CD31 antigen. The immunostaining "decorated" cell
      membranes and the membranes of intracytoplasmic vacuoles. No expression of CD31
      was found in normal adipocytes of white fat, in neoplastic cells of lipomas, or
      in multivacuolated lipoblasts of well-differentiated and myxoid liposarcomas.
      CONCLUSIONS: The spectrum of cell types that express CD31 is expanded to include
      normal and neoplastic brown fat cells. We speculate that the expression of CD31
      may play a role in the development and maintenance of the vascular network
      characterizing this specialized adipose tissue. Moreover, CD31 may inhibit the
      Bax-mediated apoptosis of brown fat cells. For practical purposes, CD31 may be
      used as an immunohistochemical marker for distinguishing between white and brown
      fat and for diagnosing hibernoma in paraffin sections.

PMID- 16594743
TI  - Gene expression profiling data in lymphoma and leukemia: review of the literature
      and extrapolation of pertinent clinical applications.
AB  - CONTEXT: Gene expression (GE) analyses using microarrays have become an important
      part of biomedical and clinical research in hematolymphoid malignancies. However,
      the methods are time-consuming and costly for routine clinical practice.
      OBJECTIVES: To review the literature regarding GE data that may provide important
      information regarding pathogenesis and that may be extrapolated for use in
      diagnosing and prognosticating lymphomas and leukemias; to present GE findings in
      Hodgkin and non-Hodgkin lymphomas, acute leukemias, and chronic myeloid leukemia
      in detail; and to summarize the practical clinical applications in tables that
      are referenced throughout the text. DATA SOURCE: PubMed was searched for
      pertinent literature from 1993 to 2005. CONCLUSIONS: Gene expression profiling of
      lymphomas and leukemias aids in the diagnosis and prognostication of these
      diseases. The extrapolation of these findings to more timely, efficient, and cost
      effective methods, such as flow cytometry and immunohistochemistry, results in
      better diagnostic tools to manage the diseases. Flow cytometric and
      immunohistochemical applications of the information gained from GE profiling
      assist in the management of chronic lymphocytic leukemia, other low-grade B-cell
      non-Hodgkin lymphomas and leukemias, diffuse large B-cell lymphoma, nodular
      lymphocyte-predominant Hodgkin lymphoma, and classic Hodgkin lymphoma. For
      practical clinical use, GE profiling of precursor B acute lymphoblastic leukemia,
      precursor T acute lymphoblastic leukemia, and acute myeloid leukemia has
      supported most of the information that has been obtained by cytogenetic and
      molecular studies (except for the identification of FLT3 mutations for molecular
      analysis), but extrapolation of the analyses leaves much to be gained based on
      the GE profiling data.

PMID- 16594744
TI  - Herbal remedies: effects on clinical laboratory tests.
AB  - CONTEXT: Complementary and alternative medicine (herbal medicines) can affect
      laboratory test results by several mechanisms. OBJECTIVE: In this review,
      published reports on effects of herbal remedies on abnormal laboratory test
      results are summarized and commented on. DATA SOURCES: All published reports
      between 1980 and 2005 with the key words herbal remedies or alternative medicine
      and clinical laboratory test, clinical chemistry test, or drug-herb interaction
      were searched through Medline. The authors' own publications were also included.
      Important results were then synthesized. DATA SYNTHESIS: Falsely elevated or
      falsely lowered digoxin levels may be encountered in a patient taking digoxin and
      the Chinese medicine Chan Su or Dan Shen, owing to direct interference of a
      component of Chinese medicine with the antibody used in an immunoassay. St John's
      wort, a popular herbal antidepressant, increases clearance of many drugs, and
      abnormally low cyclosporine, digoxin, theophylline, or protease inhibitor
      concentrations may be observed in a patient taking any of these drugs in
      combination with St John's wort. Abnormal laboratory results may also be
      encountered owing to altered pathophysiology. Kava-kava, chaparral, and germander
      cause liver toxicity, and elevated alanine aminotransferase, aspartate
      aminotransferase, and bilirubin concentrations may be observed in a healthy
      individual taking such herbal products. An herbal product may be contaminated
      with a Western drug, and an unexpected drug level (such as phenytoin in a patient
      who never took phenytoin but took a Chinese herb) may confuse the laboratory
      staff and the clinician. CONCLUSIONS: Use of alternative medicines may
      significantly alter laboratory results, and communication among pathologists,
      clinical laboratory scientists, and physicians providing care to the patient is
      important in interpreting these results.

PMID- 16594745
TI  - Use of microsatellite analysis in detection of tumor lineage as a cause of death
      in a liver transplant patient.
AB  - Malignant tumors are a significant cause of long-term morbidity and mortality in
      allograft recipients. Most solid tumors in transplant recipients are assumed to
      arise de novo in the setting of chronic immunosuppressive therapy; however, there
      have been instances in which malignant tumors have been transplanted in donated
      tissue from apparently healthy donors. We report a case of a 49-year-old liver
      transplant patient who presented with metastatic melanoma 9 months after
      transplantation for hepatocellular carcinoma and who later succumbed to the
      disease. To investigate the possibility that melanoma was derived from the donor
      liver, we used a commercially available polymerase chain reaction-based
      microsatellite marker assay to perform tissue identity testing. The genetic
      profiles of the patient's original hepatocellular carcinoma and the melanoma from
      the autopsy specimen were compared with the profile of the normal donor liver
      tissue, which was still available for testing. The pattern of microsatellite
      allelic expression strongly suggested that the melanoma detected at autopsy
      originated from the transplanted liver.

PMID- 16594746
TI  - Lethal vertebral artery dissection in pregnancy: a case report and review of the
      literature.
AB  - Subarachnoid hemorrhage represents a rare event in pregnancy with a high
      mortality rate. We present the case of a 39-year-old pregnant woman who developed
      right vertebral artery dissection with subsequent massive subarachnoid hemorrhage
      with fatal outcome. The macroscopic and microscopic autopsy findings are
      described. A review of the literature with a discussion of the varied
      predisposing factors for vertebral artery dissection and subarachnoid hemorrhage
      and the rarity of these events in pregnancy is provided.

PMID- 16594747
TI  - Concurrent herpes simplex viral lymphadenitis and mantle cell lymphoma: a case
      report and review of the literature.
AB  - We report a case of localized herpes simplex virus lymphadenitis in a patient
      with mantle cell lymphoma (MCL). A 43-year-old woman with a 2-month history of
      lymphadenitis and peripheral lymphocytosis received a diagnosis of stage IV MCL
      based on histologic, flow cytometric, and immunohistochemical findings. One week
      after completion of chemotherapy, she presented with rapidly enlarging bilateral
      cervical lymph nodes, a retropharyngeal mass, and incipient respiratory
      compromise. Multiple biopsies of the cervical nodes and oropharynx that were
      submitted for morphologic, flow cytometric, and immunohistochemical studies
      revealed involvement by MCL with superimposed herpes simplex virus lymphadenitis.
      The recognition of herpes simplex virus infection with MCL is important for
      treatment as well as to rule out transformation of MCL to a higher-grade lesion.

PMID- 16594748
TI  - Primary choriocarcinoma of the lung manifesting as diffuse alveolar hemorrhage.
AB  - An autopsy case of primary pulmonary choriocarcinoma that manifested as diffuse
      alveolar hemorrhage is reported. A 44-year-old nurse presented with fever, dry
      cough, hemoptysis, and progressive dyspnea, and died after a downhill course of 2
      weeks. Chest radiographs showed diffuse parenchymal shadows throughout the entire
      lung and a nodular lesion in the right lower lobe. Findings suggestive of acute
      renal failure were not seen. The autopsy revealed primary pure choriocarcinoma of
      the right lower lobe and diffuse alveolar hemorrhage throughout the entire lung.
      Findings of small vessel vasculitis ("pulmonary alveolar capillaritis") were not
      observed, and extensive neoplastic involvement of the pulmonary vasculature was
      considered the cause of the diffuse alveolar hemorrhage. Small metastatic foci
      were found in the liver, adrenal glands, pancreas, and ovaries. This case shows
      that primary pulmonary neoplasms, on rare occasions, can produce the clinical and
      pathologic features of diffuse alveolar hemorrhage, probably through elevated
      pulmonary venous pressure caused by extensive destruction of the vasculature.

PMID- 16594749
TI  - Synchronous interdigitating dendritic cell sarcoma and B-cell small lymphocytic
      lymphoma in a lymph node.
AB  - A gradually enlarging axillary mass in a 79-year-old man was excised. The
      specimen was processed for light microscopy, immunohistochemical studies, and
      electron microscopy; gene rearrangement studies were also performed. A diagnosis
      of an interdigitating dendritic cell tumor of the lymph node and a B-cell small
      lymphocytic lymphoma occurring in the same anatomic location was made. We found
      that although rare cases of interdigitating dendritic cell tumor with an
      associated secondary malignancy have been described in the literature, to our
      knowledge, this is the first report of interdigitating dendritic cell tumor and
      synchronous neoplasm diagnosed at the same site. A possible relationship between
      the 2 disorders is also discussed.

PMID- 16594750
TI  - Tumoral calcinosis of the hand: three unusual cases with painful swelling of
      small joints.
AB  - Tumoral calcinosis is a rare ectopic calcification syndrome characterized by
      irregular soft tissue masses originally described as being found mainly in large
      joints. We report 3 cases of tumoral calcinosis that occurred in unusual
      locations, the metacarpophalageal and proximal interphalangeal joints of the
      hand. The patients were women who ranged in age from 26 to 44; all presented with
      complaints of painful swelling of the joints. Laboratory tests demonstrated
      normal serum phosphate and calcium levels. Radiologic examination disclosed para
      articular calcified masses. On surgical excision, the deep-seated calcified
      masses were attached to collateral ligaments of the joints. Milky and chalklike
      fluid was released during surgery. The masses measured 1.5, 0.9, and 0.8 cm in
      length and had irregular surfaces. Microscopically, the masses had fibrous
      capsule and the inner small cystic spaces that contained granular, calcified
      material. These cysts contained proliferating capillaries, mononuclear lymph
      plasma cells, and giant cells. No recurrences were found in any of the patients
      during the follow-up periods.

PMID- 16594752
TI  - Hodgkin lymphoma-like posttransplantation lymphoproliferative disorder.
AB  - Posttransplantation lymphoproliferative disorders (PTLD) are a heterogeneous
      group of monoclonal or polyclonal lymphoproliferative lesions that occur in
      immunosuppressed recipients following solid organ or bone marrow transplantation,
      including 4 categories: (1) early lesions (reactive plasmacytic hyperplasia, and
      infectious-mononucleosis-like PTLD), (2) polymorphic PTLD, (3) monomorphic PTLD
      (including B-cell neoplasms and T-cell neoplasms), and (4) Hodgkin lymphoma (HL)
      and HL-like PTLD in the current World Health Organization classification.
      Although HL-like PTLD has been grouped with classic HL PTLD, controversy remains
      as to whether it is truly a form of HL or whether it should be more appropriately
      considered as a form of B-cell PTLD. The current available literature data
      indicate the presence of important immunophenotypic, molecular genetic, and
      clinical differences between HL PTLD and HL-like PTLD, suggesting that HL-like
      PTLD is in fact most often a form of B-cell PTLD. Distinction from true HL may be
      important for clinical management and prognosis.

PMID- 16594751
TI  - Esophageal melanocytosis morphologic features and review of the literature.
AB  - Endoscopic or macroscopic esophageal melanocytosis is a benign clinicopathologic
      entity characterized by melanocytic proliferation in esophageal squamous
      epithelium and melanin deposition in the mucosa. Little is known about the
      etiology and natural course of this condition, although it has been suggested to
      be a precursor of primary esophageal melanoma by some authors. Following a search
      of the bibliographic databases (PubMed and Medline) regarding esophageal
      melanocytosis and melanosis, thirty-four cases of isolated esophageal
      melanocytosis (including one unpublished case from us) were found. The
      histopathologic features of esophageal melanocytosis are reviewed and its
      differential diagnosis with other pigmented esophageal lesions is discussed.

PMID- 16594753
TI  - A urethral mass in a 67-year-old woman. Papillary endothelial hyperplasia (Masson
      tumor).

PMID- 16594754
TI  - A 27-year-old woman with incidental omental nodules. Calcifying fibrous
      pseudotumor of the omentum.

PMID- 16594755
TI  - A 3 1/2-year-old child with a posterior fossa mass. Pigmented medullomyoblastoma.

PMID- 16594756
TI  - A confused 55-year-old man. Disseminated toxoplasmosis.

PMID- 16594759
TI  - A large, fungating breast mass. Secretory carcinoma with apocrine
      differentiation.

PMID- 16594758
TI  - Pneumothorax and pulmonary cyst in a 2-year-old child. Pleuropulmonary blastoma.

PMID- 16594760
TI  - An 18-year-old woman with proteinuria and renal insufficiency. C1q nephropathy.

PMID- 16594761
TI  - A 26-year-old woman with right ovarian mass. Small cell carcinoma of ovary,
      hypercalcemic type.

PMID- 16594762
TI  - A 19-year-old woman with a cervicovaginal mass and elevated serum CA 125.
      Desmoplastic small round cell tumor.

PMID- 16594763
TI  - A 75-year-old man with an asymptomatic pleural-based mass discovered on routine
      chest radiographs. Primary pleural thymoma.

PMID- 16594764
TI  - The principle of parallelism in the design of studies to estimate treatment
      effects.
AB  - An effect is a function of a cause as well as of 4 other factors: recipient,
      setting, time, and outcome variable. The principle of parallelism states that if
      a design option exists for any 1 of these 4 factors, a parallel option exists for
      each of the others. For example, effects are often estimated by drawing a
      comparison across recipients who receive different treatments. The principle of
      parallelism implies that an effect can also be estimated by drawing a comparison
      across settings, times, or outcome variables. Typologies of methodological
      options are derived from the principle of parallelism. The typologies can help
      researchers recognize a broader set of options than they would otherwise and
      thereby improve the quality of research designs.

PMID- 16594765
TI  - Testing differences between nested covariance structure models: Power analysis
      and null hypotheses.
AB  - For comparing nested covariance structure models, the standard procedure is the
      likelihood ratio test of the difference in fit, where the null hypothesis is that
      the models fit identically in the population. A procedure for determining
      statistical power of this test is presented where effect size is based on a
      specified difference in overall fit of the models. A modification of the standard
      null hypothesis of zero difference in fit is proposed allowing for testing an
      interval hypothesis that the difference in fit between models is small, rather
      than zero. These developments are combined yielding a procedure for estimating
      power of a test of a null hypothesis of small difference in fit versus an
      alternative hypothesis of larger difference.

PMID- 16594766
TI  - Local solutions in the estimation of growth mixture models.
AB  - Finite mixture models are well known to have poorly behaved likelihood functions
      featuring singularities and multiple optima. Growth mixture models may suffer
      from fewer of these problems, potentially benefiting from the structure imposed
      on the estimated class means and covariances by the specified growth model. As
      demonstrated here, however, local solutions may still be problematic. Results
      from an empirical case study and a small Monte Carlo simulation show that failure
      to thoroughly consider the possible presence of local optima in the estimation of
      a growth mixture model can sometimes have serious consequences, possibly leading
      to adoption of an inferior solution that differs in substantively important ways
      from the actual maximum likelihood solution. Often, the defaults of current
      software need to be overridden to thoroughly evaluate the parameter space and
      obtain confidence that the maximum likelihood solution has in fact been obtained.

PMID- 16594767
TI  - A better lemon squeezer? Maximum-likelihood regression with beta-distributed
      dependent variables.
AB  - Uncorrectable skew and heteroscedasticity are among the "lemons" of psychological
      data, yet many important variables naturally exhibit these properties. For scales
      with a lower and upper bound, a suitable candidate for models is the beta
      distribution, which is very flexible and models skew quite well. The authors
      present maximum-likelihood regression models assuming that the dependent variable
      is conditionally beta distributed rather than Gaussian. The approach models both
      means (location) and variances (dispersion) with their own distinct sets of
      predictors (continuous and/or categorical), thereby modeling heteroscedasticity.
      The location sub-model link function is the logit and thereby analogous to
      logistic regression, whereas the dispersion sub-model is log linear. Real
      examples show that these models handle the independent observations case readily.
      The article discusses comparisons between beta regression and alternative
      techniques, model selection and interpretation, practical estimation, and
      software.

PMID- 16594768
TI  - The meaning and suitability of various effect sizes for structured Rater x Ratee
      designs.
AB  - Four types of analysis are commonly applied to data from structured Rater x Ratee
      designs. These types are characterized by the unit of analysis, which is either
      raters or ratees, and by the design used, which is either between-units or within
      unit design. The 4 types of analysis are quite different, and therefore they give
      rise to effect sizes that differ in their substantive interpretations. In most
      cases, effect sizes based on between-ratee analysis have the least ambiguous
      meaning and will best serve the aims of meta-analysts and primary researchers.
      Effect sizes that arise from within-unit designs confound the strength of an
      effect with its homogeneity. Nonetheless, the authors identify how a range of
      effect-size types such as these serve the aims of meta-analysis appropriately.

PMID- 16594769
TI  - Paper or plastic? Data equivalence in paper and electronic diaries.
AB  - Concern has been raised about the lack of participant compliance in diary studies
      that use paper-and-pencil as opposed to electronic formats. Three studies
      explored the magnitude of compliance problems and their effects on data quality.
      Study 1 used random signals to elicit diary reports and found close matches to
      self-reported completion times, matches that could not plausibly have been
      fabricated. Studies 2 and 3 examined the psychometric and statistical equivalence
      of data obtained with paper versus electronic formats. With minor exceptions,
      both methods yielded data that were equivalent psychometrically and in patterns
      of findings. These results serve to at least partially mollify concern about the
      validity of paper diary methods.

PMID- 16594770
TI  - Paper and electronic diaries: Too early for conclusions on compliance rates and
      their effects--Comment on Green, Rafaeli, Bolger, Shrout, and Reis (2006).
AB  - This commentary discusses 4 issues relevant to interpretation of A. S. Green, E.
      Rafaeli, N. Bolger, P. E. Shrout, and H. T. Reis's (2006) article: (a) Self
      reported compliance in medical settings has generally been substantially higher
      than verified compliance, suggesting that this is not a rare phenomenon; (b) none
      of the studies reported in Green et al. explicitly verified paper diary
      compliance; (c) the impact of participant motivation on diary compliance is
      unknown, and it may be difficult for researchers to accurately assess it in their
      own studies; and (d) without objective verification of diary compliance, analysis
      of the effects of noncompliance on data quality is difficult to interpret. The
      authors conclude that compliance in paper diaries and the effects of
      noncompliance on data quality are still unsettled issues.

PMID- 16594771
TI  - Paper and plastic in daily diary research: Comment on Green, Rafaeli, Bolger,
      Shrout, and Reis (2006).
AB  - The authors applaud A. S. Green, E. Rafaeli, N. Bolger, P. E. Shrout, and H. T.
      Reis's (2006) response to one-sided comparisons of paper versus electronic
      (plastic) diary methods and hope that it will stimulate more balanced
      considerations of the issues involved. The authors begin by highlighting areas of
      agreement and disagreement with Green et al. The authors review briefly the
      broader literature that has compared paper and plastic diaries, noting how recent
      comparisons have relied on study designs and methods that favor investigators'
      allegiances. The authors note some sorely needed data for the evaluation of the
      implications of paper versus plastic for the internal and external validity of
      research. To facilitate evaluation of the existing literature and assist in the
      design of future studies, the authors offer a balanced comparison of paper and
      electronic diary methods across a range of applications. Finally, the authors
      propose 2 study designs that offer fair comparisons of paper and plastic diary
      methods.

PMID- 16594772
TI  - Dear diary, is plastic better than paper? I can't remember: Comment on Green,
      Rafaeli, Bolger, Shrout, and Reis (2006).
AB  - In this commentary, the authors discuss the implications of A. S. Green, E.
      Rafaeli, N. Bolger, P. E. Shrout, and H. T. Reis's (2006) diary studies with
      respect to memory. Researchers must take 2 issues into account when determining
      whether paper-and-pencil or handheld electronic diaries gather more trustworthy
      data. The first issue is a matter of prospective memory, and the second is a
      matter of reconstructive memory. The authors review the research on these issues
      and conclude that regardless of the type of diary researchers use, several
      factors can conspire to produce prompt--but inaccurate--data.

PMID- 16594774
TI  - Attentional networks in normal aging and Alzheimer's disease.
AB  - By combining a flanker task and a cuing task into a single paradigm, the authors
      assessed the effects of orienting and alerting on conflict resolution and
      explored how normal aging and Alzheimer's disease (AD) modulate these attentional
      functions. Orienting failed to enhance conflict resolution; alerting was most
      beneficial for trials without conflict, as if acting on response criterion rather
      than on information processing. Alerting cues were most effective in the older
      groups--healthy aging and AD. Conflict resolution was impaired only in AD.
      Orienting remained unchanged across groups. These findings provide evidence of
      different life span developmental and clinical trajectories for each attentional
      network.

PMID- 16594775
TI  - Patterns of prospective and retrospective memory impairment in preclinical
      Alzheimer's disease.
AB  - Forty-six preclinical Alzheimer's disease (AD) participants and 188 nondemented
      control persons from the Kungsholmen Project (L. Backman et al., 2004) were
      compared on prospective memory (ProM) and retrospective memory (RetM) tasks 3
      years before dementia diagnosis. The preclinical AD participants showed deficits
      in both ProM and RetM. Most interestingly, logistic regression analyses revealed
      that ProM made an independent contribution to the prediction of AD over and above
      that of RetM. This finding suggests that ProM and RetM tap partly different
      cognitive operations. Furthermore, within the ProM task, both the retrospective
      and prospective components were similarly impaired in preclinical AD. Within
      RetM, the preclinical AD participants were impaired on indices of encoding,
      storage (forgetting), and retrieval of information. Hence, the findings indicate
      a rather global episodic memory impairment in preclinical AD that cuts across
      type of memory assessed (ProM and RetM) as well as across different components of
      both the ProM and RetM tasks.

PMID- 16594776
TI  - Differentiating among prefrontal substrates in psychopathy: neuropsychological
      test findings.
AB  - Frontal lobe and consequent executive dysfunction have long been related to
      psychopathy. More recently, there have been suggestions that specific regions of
      frontal cortex, rather than all of frontal cortex, may be implicated in
      psychopathy. To examine this issue, the authors presented 25 individuals with
      psychopathy and 30 comparison individuals with measures preferentially indexing
      the orbitofrontal cortex (OFC; object alternation task), dorsolateral prefrontal
      cortex (DLPFC; spatial alternation task), and anterior cingulate cortex (ACC;
      number-Stroop reading and counting tasks). The individuals with psychopathy
      showed significant impairment on the measure preferentially sensitive to OFC
      functioning. In contrast, the 2 groups did not show impairment on the measures
      preferentially sensitive to the functioning of the DLPFC or ACC. These results
      are interpreted with reference to executive dysfunction accounts of the disorder.

PMID- 16594777
TI  - Neuropsychological functioning in girls with attention-deficit/hyperactivity
      disorder with and without learning disabilities.
AB  - The authors' goal was to assess neuropsychological performance in girls with
      attention-deficit/hyperactivity disorder (ADHD) and evaluate the role of comorbid
      learning disabilities (LDs). Participants were 140 girls with ADHD and 122 girls
      without ADHD, ages 6-17 years. Neuropsychological performance was measured in a
      standardized manner, blind to clinical status. LD was defined by a combined
      regression-based and low-achievement classification. ADHD was associated with
      modest, but significant, neuropsychological impairment, as measured with an
      aggregate measure of performance and with the Stroop Color-Word Test, independent
      of age, social class, IQ, and psychiatric comorbidity. Neuropsychological
      deficits were most pronounced in girls with both ADHD and an LD and in those
      without medications. These results extend to females the previously documented
      association of LDs with neuropsychological functioning in males with ADHD.

PMID- 16594778
TI  - Efficiency of callosal transfer and hemispheric interaction.
AB  - The corpus callosum (CC) is essential to hemispheric interaction, but it is
      unclear how individual callosal properties affect interaction between the
      cerebral hemispheres. A number of studies have demonstrated some relationship
      between morphology or structure of the CC and measures of hemispheric
      interaction. However, to the authors' knowledge, none of these studies has been
      able to show a clear, direct relationship between a behavioral measure of
      transfer speed through the CC, interhemispheric transfer time (IHTT), and a
      behavioral measure of hemispheric interaction. Eighty participants were tested
      over 6 sessions on 2 tasks assessing IHTT and hemispheric interaction. The
      Poffenberger paradigm was used to measure IHTT, and a divided split-visual-field
      letter-matching task was used to assess hemispheric interaction. A significant
      correlation that could not be accounted for by other factors such as functional
      lateralization, handedness, age, sex, or attention was found between these 2
      measures. These results are discussed in relation to CC morphology and structure
      and functional and structural hemispheric lateralization.

PMID- 16594779
TI  - Mis-attribution errors in Alzheimer's disease: the illusory truth effect.
AB  - Patients with mild Alzheimer's disease (AD) and age-matched controls were
      compared on a series of tasks designed to measure errors of mis-attribution, the
      act of attributing a memory or idea to an incorrect source. Mis-attribution was
      indexed through the illusory truth effect, the tendency for participants to judge
      previously encountered information to be true. Cognitive theories have suggested
      that the illusory truth effect reflects the mis-attribution of experimentally
      produced familiarity (a nonspecific sense that an item has been previously
      encountered) to the veracity of previously encountered information. Consistent
      with earlier suggestions that AD impairs both familiarity and recollection
      (specific memory for contextual details of the study episode), AD patients
      demonstrated significantly fewer mis-attribution errors under conditions in which
      the illusory truth effect is thought to rely on relative familiarity (uncued
      condition), but more mis-attribution errors under conditions thought to rely on
      relative amounts of contextual recollection (cued condition). These results help
      further specify the precise nature of memory impairments in AD.

PMID- 16594780
TI  - When memory does not fail: familiarity-based recognition in mild cognitive
      impairment and Alzheimer's disease.
AB  - Recognition can be guided by familiarity, a restricted form of retrieval devoid
      of contextual recall, or by recollection, which occurs when retrieval is
      sufficient to support the full experience of remembering an episode. Recollection
      and familiarity were disentangled by testing recognition memory using silhouette
      object drawings, high target-foil resemblance, and both yes-no and forced-choice
      procedures. Theoretically, forced-choice recognition could be mediated by
      familiarity alone. Alzheimer's disease and its preclinical stage, mild cognitive
      impairment (MCI), were associated with memory impairments that were greater on
      the yes-no test. Remarkably, forced-choice recognition was unequivocally normal
      in patients with MCI compared with age-matched controls. Neuropathology in
      hippocampus and entorhinal cortex, known to be present in MCI, presumably
      disrupted recollection while leaving familiarity-based recognition intact.

PMID- 16594781
TI  - Structure of four executive functioning tests in healthy older adults.
AB  - The authors examined the factor structure of 4 indicators of executive
      functioning derived from 2 new (i.e., Hayling and Brixton) and 2 traditional
      (i.e., Stroop and Color Trails) tests. Data were from a cross-sectional sample of
      55- to 85-year-old healthy adults (N=427) from the Victoria Longitudinal Study.
      Confirmatory factor analysis (LISREL 8.52) tested both a 2-factor model of
      Inhibition (Hayling, Stroop) and Shifting (Brixton, Color Trails) and a single
      factor model. The 2-factor model did not fit the data because the covariance
      matrix of the factors was not positive definite. The single-factor model fit the
      data well, chi(2)(2, N=427)=0.32, p=.85, root-mean-square error of approximation
      (RMSEA)=.00, comparative fit index (CFI)=1.00, goodness-of-fit index (GFI)=1.00.
      Moreover, the single-factor structure of executive functioning was invariant
      (configural and metric) across gender, and invariant (configural with limited
      metric) across age. Structural relations showed that poorer executive functioning
      performance was related to older age and lower fluid intelligence, chi(2)(11,
      N=418)=23.04, p=.02, RMSEA=.05, CFI=.97, GFI=.98.

PMID- 16594782
TI  - Cognitive processes related to gait velocity: results from the Einstein Aging
      Study.
AB  - The authors examined the relationship between cognition and gait velocity,
      performed with and without interference, in elderly participants.
      Neuropsychological test scores from 186 cognitively normal elders were submitted
      to factor analysis that yielded 3 factors: Verbal IQ, Speed/Executive Attention,
      and Memory. Regression analyses revealed that these factors were significant
      predictors of variance in gait velocity, but the relationship varied as a
      function of task condition. All 3 factors predicted gait velocity without
      interference. However, the Speed/Executive Attention and Memory factors but not
      Verbal IQ predicted gait velocity in the interference condition. These findings
      suggest that gait velocity and cognitive function may have both shared and
      independent brain substrates. Future studies should explore gait velocity and
      cognitive function as predictors of dementia and falls.

PMID- 16594783
TI  - Loss of emotional experience after traumatic brain injury: findings with the
      startle probe procedure.
AB  - The authors used affective modulation of the eyeblink startle response to examine
      the impact of traumatic brain injury (TBI) on emotional reactions to pictures.
      Participants were 13 individuals with severe TBI and 24 controls. Participants
      were presented with pictures that differed in affective valence (e.g., mutilated
      bodies, erotic couples, and household objects) while the eyeblink startle
      response to an acoustic probe was measured. Startle amplitude was used to assess
      valence of emotional response, and startle latency was used to index interest in
      the pictures. Subjective ratings of the affect and arousal elicited by the
      various pictures were also obtained. TBI impaired startle potentiation to
      unpleasant pictures but not startle attenuation to pleasant pictures. Further,
      subjective ratings indicated that TBI participants found unpleasant pictures less
      arousing than did controls. The results are consistent with recent evidence of
      differential impairment in negative versus positive emotions after TBI and are
      discussed in relation to 2 competing explanations of startle modulation.

PMID- 16594784
TI  - Hemispheric differences for identification of words and nonwords in Urdu-English
      bilinguals.
AB  - Hemispheric asymmetry was examined for Urdu-English bilinguals identifying
      printed Urdu words and nonwords, separated Urdu letter strings, digits, and
      English nonwords. In all cases, fewer errors occurred when stimuli were presented
      to the right visual field/left hemisphere (RVF/LH) than to the left visual
      field/right hemisphere (LVF/RH). Qualitative error patterns suggested that
      separated Urdu letter strings were processed more serially than Urdu letter
      strings joined to form words or pronounceable nonwords and more serially on
      RVF/LH than on LVF/RH trials. This qualitative laterality effect is similar to
      that found for Hebrew and Arabic but opposite that found for English and suggests
      that the qualitative manner of processing printed verbal material is influenced
      by language-specific factors such as scanning direction, orthographic-to
      phonological mapping rules, and morphology.

PMID- 16594785
TI  - Explicit category learning in Parkinson's disease: deficits related to impaired
      rule generation and selection processes.
AB  - The present study examined the source of explicit category learning deficits
      previously noted in patients with Parkinson's disease (PD). Task stimuli
      consisted of 4 binary-valued cues that together determined category assignment,
      although some cues were more important for the categorization decision.
      Participants verbalized the hypotheses being tested to provide several measures
      of the hypothesis testing. Analyses of these verbal protocols indicated that PD
      patients were impaired on rule generation and selection but not rule shifting.
      Patients had particular difficulty noting the relative importance of the cues.
      Specific aspects of performance were differently correlated with
      neuropsychological measures of working memory and hypothesis testing ability.
      Together, the results suggest that the cognitive processes required for explicit
      category learning are mediated by partially distinct neural mechanisms.

PMID- 16594786
TI  - Psychology and Aging: the first 20 years.
AB  - This article provides a review of the first 20 years of Psychology and Aging, the
      American Psychological Association's first and only scholarly journal devoted to
      the topic of aging. The authors briefly summarize its history, its contributions
      to the study of aging, and its broader status as a scholarly publication. One
      theme highlighted in our review is the diversity of content in the journal
      throughout its history. Another is the strong impact that articles published in
      the journal have had on both basic and applied topics in aging. Efforts to
      encompass the breadth of topics and methodologies in aging research while
      retaining excellent quality remain the exciting but essential challenge for
      Psychology and Aging.

PMID- 16594787
TI  - Age effects in coding tasks: componential analysis and test of the sensory
      deficit hypothesis.
AB  - Multiple forms of a symbol-digit substitution task were used to provide a
      componential analysis of age differences in coding task performance. The results
      demonstrated age differences in feature encoding, memory, and visual search. A
      2nd experiment was conducted with young adults to investigate a sensory deficit
      as a locus of age differences. The spatial contrast sensitivity deficit of older
      adults was simulated on forms by applying a digital filter. Persons in the age
      simulated contrast condition performed worse than those in the normal contrast
      condition. The stimulus degradation effect was linked to visual search speed. The
      study illustrates the utility of componential analysis and offers direct support
      for the hypothesis that sensory deficits affect performance on tasks used to
      assess intelligence.

PMID- 16594788
TI  - Does expanded retrieval produce benefits over equal-interval spacing?
      Explorations of spacing effects in healthy aging and early stage Alzheimer's
      disease.
AB  - Three experiments explored different schedules of retrieval practice in young
      adults, older adults, and individuals with dementia of the Alzheimer type. In
      each experiment, an initial acquisition phase was presented in which participants
      studied or attempted to retrieve response words to cues, followed by a later cued
      recall test. Experiment 1 produced a benefit of expanded retrieval over equal
      interval retrieval during acquisition, but this benefit was lost in final cued
      recall. In Experiments 2 and 3, participants received corrective feedback during
      acquisition and modified spacing schedules. There was again no evidence of a
      difference between expanded and equal-interval conditions in final cued recall.
      Discussion focuses on the potential benefits and costs of expanded retrieval on a
      theoretical and applied level.

PMID- 16594789
TI  - Eye movements of young and older adults while reading with distraction.
AB  - The authors used eye-tracking technology to examine young and older adults'
      online performance in the reading in distraction paradigm. Participants read
      target sentences and answered comprehension questions following each sentence. In
      some sentences, single-word distracters were presented in either italic or red
      font. Distracters could be related or unrelated to the target text. Online
      measures, including probability of fixation, fixation duration, and number of
      fixations to distracting text, revealed no age differences in text processing.
      However, young adults did have an advantage over older adults in overall reading
      time and text comprehension. These results provide no support for an inhibition
      deficit account of age differences in the reading in distraction paradigm, but
      are consistent with J. Dywan and W. E. Murphy's (1996) suggestion that older
      adults are less able than the young to distinguish target and distracter
      information held in working memory.

PMID- 16594790
TI  - Selective preference in visual fixation away from negative images in old age? An
      eye-tracking study.
AB  - Recent studies have suggested that older individuals selectively forget negative
      information. However, findings on a positivity effect in the attention of older
      adults have been more mixed. In the current study, eye tracking was used to
      record visual fixation in nearly real-time to investigate whether older
      individuals show a positivity effect in their visual attention to emotional
      information. Young and old individuals (N = 64) viewed pairs of synthetic faces
      that included the same face in a nonemotional expression and in 1 of 4 emotional
      expressions (happiness, sadness, anger, or fear). Gaze patterns were recorded as
      individuals viewed the face pairs. Older adults showed an attentional preference
      toward happy faces and away from angry ones; the only preference shown by young
      adults was toward afraid faces. The age groups were not different in overall
      cognitive functioning, suggesting that these attentional differences are specific
      and motivated rather than due to general cognitive change with age.

PMID- 16594791
TI  - Why do older adults have difficulty following conversations?
AB  - Age-related declines in understanding conversation may be largely a consequence
      of perceptual rather than cognitive declines. B. A. Schneider, M. Daneman, D. R.
      Murphy, and S. Kwong-See (2000) showed that age-related declines in comprehending
      single-talker discourse could be eliminated when adjustments were made to
      compensate for the poorer hearing of older adults. The authors used B. A.
      Schneider et al.'s methodology to investigate age-related differences in
      comprehending 2-person conversations. Compensating for hearing difficulties did
      not eliminate age-related differences when the 2 talkers were spatially separated
      by 9 degrees or 45 degrees azimuth, but it did when the talkers' contributions
      came from one central location. These findings suggest that dialogue poses more
      of a problem for older than for younger adults, not because of the additional
      cognitive requirements of having to follow 2 talkers rather than 1, but because
      older adults are not as good as younger adults at making use of the auditory cues
      that are available for helping listeners perceptually segregate the contributions
      of 2 spatially separated talkers.

PMID- 16594792
TI  - Age and sex differences in reaction time in adulthood: results from the United
      Kingdom Health and Lifestyle Survey.
AB  - Reaction times (RTs) slow and become more variable with age. Research samples are
      typically small, biased, and of restricted age range. Consequently, little is
      known about the precise pattern of change, whereas evidence for sex differences
      is equivocal. The authors reanalyzed data for 7,130 adult participants in the
      United Kingdom Health and Lifestyle Survey, originally reported by F. A. Huppert
      (1987). The authors modeled the age differences in simple and 4-choice reaction
      time means and variabilities and tested for sex differences. Simple RT shows
      little slowing until around 50, whereas choice RT slows throughout the adult age
      range. The aging of choice RT variability is a function of its mean and the error
      rate. There are significant sex differences, most notably for choice RT
      variability.

PMID- 16594793
TI  - Aging and the detection of observer and moving object collisions.
AB  - The authors examined age-related differences in the detection of collision
      events. Older and younger observers were presented with displays simulating
      approaching objects that would either collide or pass by the observer. In 4
      experiments, the authors found that older observers, as compared with younger
      observers, had less sensitivity in detecting collisions with an increase in
      speed, at shorter display durations, and with longer time-to-contact conditions.
      Older observers also had greater difficulty when the scenario simulated observer
      motion, suggesting that older observers have difficulty discriminating object
      motion expansion from background expansion from observer motion. The results of
      these studies support the expansion sensitivity hypothesis-that age-related
      decrements in detecting collision events involving moving objects are the result
      of a decreased sensitivity to recover expansion information.

PMID- 16594794
TI  - Age-related binding deficits and the content of false memories.
AB  - The authors examined effects of age-related binding deficits on feature
      information in false memories for imagined objects (e.g., lollipop) that were
      similar in shape to seen objects (e.g., magnifying glass). In Experiment 1,
      location memory for seen objects was lower in older than younger adults and lower
      still in old-old than young-old adults. Imagined objects, when falsely called
      seen, were less likely to be attributed to the location of similar seen objects
      (i.e., congruent attributions) by old-old than young-old adults. In Experiment 2,
      for younger adults, displaying seen objects for less time (1 s vs. 4 s) reduced
      both location memory for seen objects and congruent attributions for false
      memories. Thus, binding deficits may influence the specific content of false
      memories.

PMID- 16594795
TI  - Aging selectively impairs recollection in recognition memory for pictures:
      evidence from modeling and receiver operating characteristic curves.
AB  - Young and older adults were tested on recognition memory for pictures. The
      Yonelinas high threshold (YHT) model, a formal implementation of 2-process
      theory, fit the response distribution data of both young and older adults
      significantly better than a normal unequal variance signal-detection model.
      Consistent with this finding, nonlinear z-transformed receiver operating
      characteristic curves were obtained for both groups. Estimates of recollection
      from the YHT model were significantly higher for young than for older adults.
      This deficit was not a consequence of a general decline in memory; older adults
      showed comparable overall accuracy and in fact a nonsignificant increase in their
      familiarity scores. Implications of these results for theories of recognition
      memory and the mnemonic deficit associated with aging are discussed.

PMID- 16594796
TI  - Recollection and familiarity in recognition memory: adult age differences and
      neuropsychological test correlates.
AB  - Dual process theories account for age-related changes in memory by proposing that
      old age is associated with deficits in recollection together with invariance in
      familiarity. The authors evaluated this proposal in recognition by examining
      recollection and familiarity estimates in young and older adults across 3 process
      estimation methods: inclusion/exclusion, remember/know, and receiver operating
      characteristics (ROC). Consistent with a previous literature review (Light,
      Prull, LaVoie, & Healy, 2000), the authors found age invariance in familiarity
      when process estimates were derived from the inclusion/exclusion method, but the
      authors found age differences favoring the young when familiarity estimates were
      derived from the remember/know and ROC methods. Recollection estimates were lower
      for older adults in all 3 methods. Recollection and familiarity had variable
      relationships with frontal- and temporal-lobe measures of neuropsychological
      functioning in older adults, depending on which method was used to generate
      process estimates. These data suggest that although recollection deficits appear
      to be the rule in aging, not all estimates of familiarity show age invariance.

PMID- 16594797
TI  - Relationship between age and aspects of depression: consistency and reliability
      across two longitudinal studies.
AB  - In this study, the authors examined cross-sectional and longitudinal age and
      gender differences in each of the Center for Epidemiological Studies Depression
      Scale's 4 subscales of depressive symptomatology. Two independent studies (Sample
      1 = 2,076; Sample 2 = 943) were used for purposes of establishing stability of
      findings. Results indicate a reasonable degree of stability among adults under 70
      years of age. However, there were significant age-related increases in somatic
      symptoms and lack of well-being after approximately 70 years of age, whereas
      symptoms related to depressed affect and interpersonal problems remained stable.
      Notably, depressive affect symptoms remained stable given significant age-related
      somatic changes. The addition of comorbid physical illness to the analysis did
      not reduce the association between age and depressive symptoms, indicating that
      part of the association was not substantially accounted for by physical health.

PMID- 16594798
TI  - Flashbulb memories and posttraumatic stress reactions across the life span: age
      related effects of the German occupation of Denmark during World War II.
AB  - A representative sample of older Danes were interviewed about experiences from
      the German occupation of Denmark in World War II. The number of participants with
      flashbulb memories for the German invasion (1940) and capitulation (1945)
      increased with participants' age at the time of the events up to age 8. Among
      participants under 8 years at the time of their most traumatic event, age at the
      time correlated positively with the current level of posttraumatic stress
      reactions and the vividness of stressful memories and their centrality to life
      story and identity. These findings were replicated in Study 2 for self-nominated
      stressful events sampled from the entire life span using a representative sample
      of Danes born after 1945. The results are discussed in relation to posttraumatic
      stress disorder and childhood amnesia.

PMID- 16594799
TI  - Loneliness as a specific risk factor for depressive symptoms: cross-sectional and
      longitudinal analyses.
AB  - The extent to which loneliness is a unique risk factor for depressive symptoms
      was determined in 2 population-based studies of middle-aged to older adults, and
      the possible causal influences between loneliness and depressive symptoms were
      examined longitudinally in the 2nd study. In Study 1, a nationally representative
      sample of persons aged 54 and older completed a telephone interview as part of a
      study of health and aging. Higher levels of loneliness were associated with more
      depressive symptoms, net of the effects of age, gender, ethnicity, education,
      income, marital status, social support, and perceived stress. In Study 2,
      detailed measures of loneliness, social support, perceived stress, hostility, and
      demographic characteristics were collected over a 3-year period from a population
      based sample of adults ages 50-67 years from Cook County, Illinois. Loneliness
      was again associated with more depressive symptoms, net of demographic
      covariates, marital status, social support, hostility, and perceived stress.
      Latent variable growth models revealed reciprocal influences over time between
      loneliness and depressive symptomatology. These data suggest that loneliness and
      depressive symptomatology can act in a synergistic effect to diminish well-being
      in middle-aged and older adults.

PMID- 16594800
TI  - Loneliness is a unique predictor of age-related differences in systolic blood
      pressure.
AB  - A population-based sample of Caucasians, African Americans, and Latino Americans,
      50-68 years of age (M = 57.5), from Cook County, Illinois (N = 229), was tested
      to examine how loneliness and co-occurring psychosocial factors (depressive
      symptoms, perceived stress, social support, and hostility) were related to
      indices of cardiovascular and endocrine functioning. Extending prior research,
      the authors found that loneliness was associated with elevated systolic blood
      pressure (SBP) and age-related increases in SBP, net of demographic variables,
      health behavior variables, and the remaining psychosocial factors. Loneliness was
      not associated with differences in autonomic or endocrine functioning. Although
      the results are limited by the cross-sectional methods used, they are consistent
      with the hypothesis that cardiovascular disease contributes to increased
      morbidity and mortality among lonely individuals.

PMID- 16594801
TI  - Memory self-efficacy predicts memory performance: results from a 6-year follow-up
      study.
AB  - The purpose of this study was to examine the relationship between memory self
      efficacy (MSE) and a 6-year follow-up assessment of memory functioning in a
      sample of Dutch older adults. MSE was assessed by a Dutch abridged version of the
      Metamemory in Adulthood questionnaire (MIA; R. A. Dixon, D. F. Hultsch, & C.
      Hertzog, 1988; C. Hertzog, D. F. Hultsch, & R. A. Dixon, 1989; R. W. H. M. Ponds
      & J. Jolles, 1996). The total MSE score predicted memory performance at 6 years,
      as measured by the Visual Verbal Learning Task (VVLT; N. Brand & J. Jolles,
      1985). A separate analysis of the different MSE subscales indicated that the MIA
      Change score was the most salient domain-specific MSE predictor of subsequent
      memory performance after 6 years. An extreme groups analysis of the MIA Change
      score revealed a pattern of performance for those who perceived that their memory
      was worsening, performing less well on the 3 trials of the VVLT when these were
      readministered at the 6-year follow-up.

PMID- 16594802
TI  - Focusing and restricting: two aspects of motivational selectivity in adulthood.
AB  - Using a short-term longitudinal design, the authors investigated implications of
      2 facets of motivational selectivity--restricting (to few goals) and focusing (on
      central and similar goals)--for goal-pursuit investment. Participants were 20-69
      years old (Time 1, N = 177; Time 2, N = 160). Results show that motivational
      selectivity in terms of focusing (but not in terms of restricting) is associated
      with an enhanced involvement in goal pursuit (assessed 3 months later),
      irrespective of age. Structural equation models demonstrated that this
      association is completely mediated by the degree of mutual facilitation among
      goals. Furthermore, motivational selectivity increases from middle to older
      adulthood. This contributes to the maintenance of high goal involvement into
      later adulthood, despite aging-related increases in resource limitations.

PMID- 16594803
TI  - Cerebrovascular risk factors, activity limitations, and depressed mood in African
      American older adults.
AB  - This study investigated the association between cerebrovascular risk factors
      (CVRFs), physical activity limitations, and depressed mood. The 12-item Short
      Form Health Survey (SF-12) was administered to 1,034 urban African American older
      adults. A chi-square analysis demonstrated that the prevalence of depressed mood
      among those with high CVRF burden (13.4%) was significantly higher than among
      those with low vascular burden (7.6%). Physical activity limitations also
      predicted depressed mood, but this relationship did not mediate the relationship
      between cerebrovascular burden and depression. These findings highlight the
      relationships among cerebrovascular burden, physical activity limitations, and
      depressed mood among African American older adults.

PMID- 16594804
TI  - Older adults' motivated choice for technological innovation: evidence for benefit
      driven selectivity.
AB  - This study examined older adults' motivation to adopt technological innovation.
      Sixty-eight older e-mail users and nonusers discussed the use of e-mail and of
      traditional communication methods in 18 focus groups. The results show older
      adults' benefit-driven approach to new communication technology. Regardless of
      whether their decision about the new technology was positive or negative and
      irrespective of their e-mail experience, participants focused on benefits rather
      than costs. For traditional media, both costs and benefits were important.
      Results contradict the common belief that barriers such as usability problems
      determine whether older people use new technology and indicate the decisive role
      of perceived benefits for successful innovation.

PMID- 16594805
TI  - The Cognitive Interview enhances long-term free recall of older adults.
AB  - The Cognitive Interview, a retrieval-based mnemonic technique, has received only
      limited attention in its application with older adults, and based on previous
      findings, its benefit to older adults is unclear. The authors found that the
      Cognitive Interview effectively increased older adults' recall relative to
      standard recall instructions at a 3-week delay. These findings demonstrate the
      benefit of a standardized (rather than the prototypically interactive) Cognitive
      Interview as applied to perceptually impoverished, text-based stimuli. Both
      theoretical and practical implications of the findings are discussed.

PMID- 16594806
TI  - Aging and negative affect: the rise and fall and rise of anxiety and depression
      symptoms.
AB  - The relationship between aging and negative affect is dynamic and complex.
      Although prior studies have often cited lower prevalence rates of anxiety and
      mood disorders among older individuals, these studies may miss the dynamic
      relationship between symptoms and aging. To evaluate a nonlinear model of the
      relationship between aging and negative affect, the author examined measures of
      neuroticism, anxiety, and depression symptoms in a cross-sectional, community
      sample (N = 335), ages 18 to 93. Results indicated a curvilinear relationship,
      with mean symptom levels increasing during early adulthood (until the mid-30s)
      and then showing a small decline until older adulthood (the mid-70s), when
      symptoms again increase with age.

PMID- 16594807
TI  - Intellectual functioning in adults with ADHD: a meta-analytic examination of full
      scale IQ differences between adults with and without ADHD.
AB  - Although attention has been given to the intellectual functioning of children
      with attention-deficit/hyperactivity disorder (ADHD) relative to their non-ADHD
      peers, few studies have examined intellectual functioning in adults with ADHD.
      The purpose of the current investigation was to examine differences in
      intellectual ability between adults with and without ADHD via a meta-analytic
      review. Of the 33 studies meeting inclusion criteria, primary analyses focused on
      18 studies representing 1,031 adults with ADHD and 928 non-ADHD, nonclinical
      comparison adults and containing Wechsler Adult Intelligence Scale (WAIS; D.
      Wechsler, 1955, 1981, 1994) Full Scale IQ scores or estimates. A significant
      effect was found such that adults with ADHD scored lower than non-ADHD adults on
      WAIS intelligence tests. However, this difference was small and not clinically
      meaningful. The presence of several moderators reflecting characteristics of the
      ADHD samples and study methodology suggested that only a subset of adults with
      ADHD (e.g., those with comorbid disorders) may experience lower general
      intellectual ability relative to non-ADHD comparison adults. Implications of the
      findings for clinical and research settings are presented as well as suggestions
      for improving methodology and reporting in future research.

PMID- 16594808
TI  - Confirming the three-factor structure of the quality of relationships inventory
      within couples.
AB  - The current study further validates the Quality of Relationships Inventory (QRI;
      G. R. Pierce, I. G. Sarason, & B. R. Sarason, 1991) by evaluating its factor
      structure in a sample of 572 partners from 286 couples. Confirmatory factor
      analysis was used to compare 3 different models of the QRI and to investigate the
      invariance of the factor structure of the QRI across gender and across
      relationship satisfaction. Analyses revealed that a 3-factor solution--consisting
      of 3 different but interrelated factors (a 7-item support factor, a 12-item
      conflict factor, and a 6-item depth factor)--best accounted for the data. The
      authors' findings suggest that full metric invariance holds across gender and
      across relationship satisfaction in the female subsample, whereas only partial
      metric invariance could be established for relationship satisfaction in the male
      subsample.

PMID- 16594809
TI  - Factor structure of the brief symptom inventory--18 in adult survivors of
      childhood cancer: results from the childhood cancer survivor study.
AB  - The factor structure of the Brief Symptom Inventory--18 (BSI-18; L. R. Derogatis,
      2000) was investigated in a sample of adult survivors of childhood cancer
      enrolled in the Childhood Cancer Survivor Study (CCSS; N = 8,945). An exploratory
      factor analysis with a randomly chosen subsample supported a 3-factor structure
      closely corresponding to the 3 BSI-18 subscales: Depression, Anxiety, and
      Somatization. Confirmatory factor analysis with structural equation modeling
      validated this 3-dimensional structure in a separate subsample, though an
      alternative 4-factor model also fit the data. Analysis of the 3-factor model
      showed consistent fit in male and female participants. Compared with available
      community-based norms, survivors reported fewer symptoms of psychological
      distress. Together, results support the hypothesized 3-dimensional structure of
      the BSI-18 and indicate the measure may be useful in assessing psychological
      distress in this growing population of cancer survivors.

PMID- 16594810
TI  - Investigating different factor structures of the psychopathy checklist: youth
      version: confirmatory factor analytic findings.
AB  - There has been a recent push to extend the construct of psychopathy into
      adolescence, primarily as a result of the impressive reliability, validity, and
      utility of this construct in samples of adults. The value of this work rests,
      however, on creating an equally reliable and valid assessment tool for
      adolescents. One promising measure is the Psychopathy Checklist: Youth Version
      (A. E. Forth, D. S. Kosson, & R. D. Hare, 2003). The current study uses a large,
      diverse sample of serious adolescent offenders to assess the overall fit of
      various underlying factor structures of this measure and to test the equivalence
      of these models across sex and race/ethnicity. The results suggest that either a
      3- or 4-factor model provides the best overall fit and that these models are
      invariant across sex and race/ethnicity. The decision to use the 3- or 4-factor
      model will likely hinge on researchers' underlying conceptualization of
      psychopathy, specifically whether antisocial behavior is viewed as a core feature
      of this construct.

PMID- 16594812
TI  - The reliability and validity of the panic disorder self-report: a new diagnostic
      screening measure of panic disorder.
AB  - This study examined the Panic Disorder Self-Report (PDSR), a new self-report
      diagnostic measure of panic disorder based on the 4th edition of the Diagnostic
      and Statistical Manual of Mental Disorders (American Psychiatric Association,
      1994). PDSR diagnoses were compared with structured interview diagnoses of
      individuals with generalized anxiety disorder, social phobia, and panic disorder
      and nonanxious controls. Receiver operating characteristic analyses revealed that
      the PDSR showed 100% specificity and 89% sensitivity. The PDSR also demonstrated
      retest reliability, convergent and discriminant validity, and kappa agreement of
      .93 with a structured interview. Finally, the PDSR demonstrated clinical
      validity. Students who were identified as having panic disorder using the PDSR
      did not have significantly different scores on the Panic Disorder Severity Scale-
      Self-Report form (P. R. Houck, D. A. Speigel, M. K. Shear, & P. Rucci, 2002) than
      a panic disordered community sample. However, both groups had significantly
      higher scores than students identified as not meeting criteria for panic
      disorder.

PMID- 16594813
TI  - Factor structure and interpretation of the K10.
AB  - The Kessler 10 Psychological Distress Scale (K10) is a brief 10-item
      questionnaire designed to measure the level of distress and severity associated
      with psychological symptoms in population surveys. It is being used widely,
      including in the World Health Organization World Mental Health Survey, and as a
      clinical outcome measure, although little information is available about the
      structure of the measure. The factorial composition of the K10 was examined in a
      prospective community survey and cross-validated in a separate large community
      survey. The K10 was found to consist of 4 factors and a 2-factor second-order
      factor structure. This was stable across the 2 waves of the prospective study and
      the Australian National Survey of Mental Health and Well-Being. The 4 factors,
      labeled Nervous, Negative Affect, Fatigue, and Agitation, were consistent with
      the original scales from which the items were taken. The 2 second-order factors
      represent Depression and Anxiety.

PMID- 16594814
TI  - Assessing and interpreting personality change and continuity in patients treated
      for major depression.
AB  - Structural, mean- and individual-level, differential, and ipsative personality
      continuity were examined in 599 patients treated for major depression assigned to
      1 of 6 forms of a 6-month pharmaco-psychotherapy program. Covariation among
      traits from the Five Factor model remained invariant across treatment, and
      patients described themselves as slightly more extraverted, open to experience,
      agreeable and conscientious, and substantially more emotional stable after
      treatment. Trait changes were only to a small extent explained by changes in
      depression severity. There was evidence for differential, individual-level, and
      ipsative stability, with stable personality profiles in terms of shape and to a
      lesser extent in terms of scatter and elevation. Traits remain relatively stable,
      except for emotional stability, despite the depressive state and the
      psychopharmacological interventions.

PMID- 16594815
TI  - Comparison of factor structure models for the Beck Depression Inventory--II.
AB  - Factor analyses of the Beck Depression Inventory--II (A. T. Beck, R. A. Steer, &
      G. K. Brown, 1996) have frequently produced 2 different 2-factor oblique
      structures. The author used confirmatory factor analyses to compare these
      structures with a general-factor model with 2 orthogonal group factors. The
      general-factor model fit as well as or better than the 2-factor models when
      applied to item data from previous studies (3 clinical and 2 college samples).
      Communalities associated with the General Depression factor ranged from 71% to
      82%. Cognitive and Somatic group factors were indicative of intropunitiveness and
      fatigue. It was concluded that the general-factor model gives an acceptable
      empirical explanation of item covariance structure and offers a conceptual
      interpretation that is well suited to clinical practice and research.

PMID- 16594816
TI  - The validity of dietary restraint scales: comment on Stice et al. (2004).
AB  - In 4 empirical studies, E. Stice, M. Fisher, and M. R. Lowe calculated the
      correlations between some widely used dietary restraint scales and food intake.
      Failing to find substantial negative correlations, they concluded that these
      scales were invalid. The current article challenges this conclusion. For one
      thing, there is some evidence that restrained eaters do eat less than do
      unrestrained eaters under controlled experimental conditions favoring self
      control. Dietary restraint is also associated with tendencies toward
      disinhibition under conditions favoring loss of self-control; such disinhibition
      often masks (but does not invalidate) the construct of dietary restraint. For
      these and other reasons, the assessment of food intake at a single eating episode
      may not capture overall dietary restriction. Finally, how much one eats does not
      necessarily indicate whether one has eaten less than one desired to eat. The
      authors suggest that the existing restraint scales do in fact validly assess
      restriction of food intake, albeit in a more complex fashion than is evident from
      simple correlations in single episodes.

PMID- 16594818
TI  - Development of a new critical thinking test using item response theory.
AB  - The authors describe the initial development of the Wagner Assessment Test (WAT),
      an instrument designed to assess critical thinking, using the 5-faceted view
      popularized by the Watson-Glaser Critical Thinking Appraisal (WGCTA; G. B. Watson
      & E. M. Glaser, 1980). The WAT was designed to reduce the degree of successful
      guessing relative to the WGCTA by increasing the number of response alternatives
      (i.e., 80% of WGCTA items are 2-alternative, multiple-choice), a change that was
      hypothesized to result in more desirable test information and standard-error
      functions. Analyses using the 3-parameter logistic item response theory (IRT)
      model in a sample of undergraduates (N = 407) supported this prediction, even
      when the WAT item pool was shortened to match the length of the WGCTA. Convergent
      validity between full-pool IRT score estimates was r = .69. Implications for
      subsequent research on IRT-based measurement of critical thinking are discussed.

PMID- 16594819
TI  - The reliability and validity of the Perceived Stigmatization Questionnaire (PSQ)
      and the Social Comfort Questionnaire (SCQ) among an adult burn survivor sample.
AB  - In this study, 361 adult burn survivors completed the Perceived Stigmatization
      Questionnaire (PSQ), the Social Comfort Questionnaire (SCQ), and other measures.
      Both the PSQ and SCQ had good internal consistency indices. Factor analysis of
      the PSQ yielded 3 factors (absence of friendly behavior, confused/staring
      behavior, and hostile behavior). The SCQ had 1 factor. Conjoint factor analysis
      with measures of related constructs (body esteem, body-esteem importance,
      depression, social support) suggested that PSQ and SCQ measure distinct
      constructs. Correlations with the related psychosocial constructs and burn
      characteristics suggested the PSQ and SCQ have good convergent and discriminant
      validity. Limitations of the study are discussed.

PMID- 16594820
TI  - The factorial structure of the Dutch translation of the inventory of
      interpersonal problems: a test of the long and short versions.
AB  - In this article, the authors study the factorial structure of 2 versions (64
      items and 32 items) of the Dutch translation of the Inventory of Interpersonal
      Problems (IIP; L. M. Horowitz, L. E. Alden, J. S. Wiggins, & A. L. Pincus, 2000)
      in both a clinical sample (n = 382) and a student sample (n = 287). First, the
      authors test whether both inventories are constituted by correlated uni
      dimensional subscales, and they conclude that this is true only for the short
      version. Second, the authors study whether the correlations between the subscales
      follow a circumplex pattern. This proves to be true for both versions.
      Coefficients alpha and correlations between the IIP-64 and IIP-32 subscales are
      discussed.

PMID- 16594821
TI  - The dimensions of change in therapeutic community treatment instrument.
AB  - In this article, the authors describe the refinement and preliminary evaluation
      of the Dimensions of Change in Therapeutic Community Treatment Instrument (DCI),
      a measure of treatment process. In Study 1, a 99-item DCI, administered to a
      cross-sectional sample of substance abuse clients (N = 990), was shortened to 54
      items on the basis of results from confirmatory factor analyses and item response
      theory invariance tests. In Study 2, confirmatory factor analyses of the 54-item
      DCI, completed by a longitudinal cohort of 993 clients, established and validated
      an 8-factor solution across 2 subpopulations (adults and adolescents) and 2 time
      points (treatment entry and 30-days postentry). The results of the 2 studies are
      encouraging and support use of the 54-item DCI as a tool to measure treatment
      process.

PMID- 16594822
TI  - Orthogonal higher order structure of the Wechsler Intelligence Scale For Children
      -fourth edition.
AB  - According to J. B. Carroll's (1993) 3-stratum theory, performance on any subtest
      reflects a mixture of both 2nd-order and 1st-order factors. To disentangle these
      influences, variance explained by the general factor should be extracted first.
      The 1st-order factors are then residualized, leaving them orthogonal to the
      general factor and each other. When these methods were applied to the WISC-IV
      standardization sample, the general factor accounted for the greatest amount of
      common (71.3%) and total (38.3%) variance. The largest contribution by a first
      order factor was 6.5% of total variance. It was recommended that interpretation
      of the WISC-IV not discount the strong general factor.

PMID- 16594823
TI  - MMPI--2 Code-Type Congruence of Injured Workers.
AB  - In this study, the authors examined the stability of Minnesota Multiphasic
      Personality Inventory--2 (J. N. Butcher, W. G. Dahlstrom, J. R. Graham, A.
      Tellegen, & B. Kaemmer, 1989) code types in a sample of 94 injured workers with a
      mean test-retest interval of 21.3 months (SD = 14.1). Congruence rates for
      undefined code types were 34% for high-point codes, 22% for 2-point codes, and
      22% for 3-point codes. The data provide tentative evidence suggesting that
      defined code types are more stable than undefined code types. Cohen's kappa, a
      statistic that controls for chance agreement, was calculated for each clinical
      scale for both 2-point and 3-point code types. Only 2 of the 20 kappa
      coefficients were not significant at the p = .05 level.

PMID- 16594824
TI  - Construal levels and self-control.
AB  - The authors propose that self-control involves making decisions and behaving in a
      manner consistent with high-level versus low-level construals of a situation.
      Activation of high-level construals (which capture global, superordinate, primary
      features of an event) should lead to greater self-control than activation of low
      level construals (which capture local, subordinate, secondary features). In 6
      experiments using 3 different techniques, the authors manipulated construal
      levels and assessed their effects on self-control and underlying psychological
      processes. High-level construals led to decreased preferences for immediate over
      delayed outcomes, greater physical endurance, stronger intentions to exert self
      control, and less positive evaluations of temptations that undermine self
      control. These results support a construal-level analysis of self-control.

PMID- 16594825
TI  - Birds of a feather and birds flocking together: physical versus behavioral cues
      may lead to trait- versus goal-based group perception.
AB  - Entitativity perception refers to the perception of a collection of individuals
      as a group. The authors propose 2 perceptual-inferential bases of entitativity
      perception. First, perceivers would expect a collection of individuals with
      similar physical traits to possess common psychological traits. Second,
      perceivers watching a group of individuals engage in concerted behavior would
      infer that these individuals have common goals. Thus, both similarity in physical
      traits (e.g., same skin color) and concerted collective behavior (e.g., same
      movement) would evoke perception of group entitativity. Results from 5
      experiments show that same group movement invariably leads to common goal
      inferences, increased perceived cohesiveness, and increased perceived
      entitativity. Moreover, same skin color evokes inferences of group traits and
      increases perceived homogeneity and perceived entitativity but only when skin
      color is diagnostic of group membership.

PMID- 16594826
TI  - The effect of target group size on risk judgments and comparative optimism: the
      more, the riskier.
AB  - In 5 experiments, college students exhibited a group size effect on risk
      judgments. As the number of individuals in a target group increased, so did
      participants' judgments of the risk of the average member of the group for a
      variety of negative life events. This happened regardless of whether the stimuli
      consisted of photographs of real peers or stick-figure representations of peers.
      As a result, the degree to which participants exhibited comparative optimism
      (i.e., judged themselves to be at lower risk than their peers) also increased as
      the size of the comparison group increased. These results suggest that the
      typical comparative optimism effect reported so often in the literature might be,
      at least in part, a group size effect. Additional results include a group size
      effect on judgments of the likelihood that the average group member will
      experience positive and neutral events and a group size effect on perceptual
      judgments of the heights of stick figures. These latter results, in particular,
      support the existence of a simple, general cognitive mechanism that integrates
      stimulus numerosity into quantitative judgments about that stimulus.

PMID- 16594827
TI  - Two faces of (dis)similarity in affective judgments of persons: contrast or
      assimilation effects revealed by morphs.
AB  - The authors investigated the role of dissimilarity on context effects in person
      perception. Most research predicts similar people to be similarly evaluated and
      different people to be contrasted with each other. However, some research
      suggests that similarity may enhance comparison and contrast. To explain these
      opposite effects, the authors argue that dissimilarity may influence 2 different
      processes with opposite consequences. Dissimilarity may decrease common
      categorization and thus the likelihood of comparison, resulting in reduced
      contrast, whereas during comparison itself dissimilarity may increase the
      perceived dissimilarity of features and thereby increase contrast. To investigate
      this, the authors conducted 3 studies in which they manipulated dissimilarity by
      inserting morphs that were related or unrelated to the context and target faces
      before judgments were made. The results indicate that dissimilarity may affect
      the likelihood and the outcome of comparison, with contrasting consequences.

PMID- 16594828
TI  - Intentions in teasing: when "just kidding" just isn't good enough.
AB  - Teasing is ambiguous. Although the literal content of a tease is, by definition,
      negative, seldom do teasers intend for their tease to be taken literally. Toward
      this aim, teasers often attempt to mitigate the negative surface content of the
      tease by communicating via gesture, facial expression, or tone of voice that they
      are "just kidding." The research presented here suggests that such attempts often
      fall on deaf ears. Despite teasers' attempts to mitigate the tease, targets are
      often unaware of--and unmoved by--the teaser's benign intentions. As a result,
      teasers and targets systematically differ in their perceptions of teasing:
      Although it is often seen as innocent and playful by the teaser, it tends to be
      construed as considerably more malicious by the target.

PMID- 16594829
TI  - Us without them: evidence for an intragroup origin of positive in-group regard.
AB  - Four experiments examined whether group formation and positive in-group regard
      require interaggregate comparison as the in-group-requires-an-out-group
      assumption of the metacontrast principle implies. The authors fostered novel
      social aggregates with or without a contrasting aggregate with which members
      could compare and varied intra-aggregate factors (interaction or
      interdependence). Regardless of whether interaggregate comparison was feasible,
      the intra-aggregate factors increased the perceived entitativity of the aggregate
      and positive regard toward the aggregate (i.e., social attraction and cooperation
      among members). Mediation analyses were consistent with the possibility that the
      intra-aggregate factors promoted entitativity, which in turn promoted in-group
      regard. These data suggest that group formation and in-group regard have
      intragroup origins and do not require comparison with a contrasting social
      aggregate.

PMID- 16594830
TI  - Positive and negative opinion modeling: the influence of another's similarity and
      dissimilarity.
AB  - Modeling research that has focused on the effects of observing similar others
      appears to have underestimated the influence of observing dissimilar others. Two
      experiments demonstrated that observing a model express liking for a piece of
      music induced more favorable opinions of the music (positive modeling) when the
      model was similar to the participant observer in relevant opinions, and more
      negative opinions (negative modeling) when the model was dissimilar to the
      participant in relevant opinions. Of note, this pattern was more pronounced when
      participants also believed their general backgrounds were dissimilar rather than
      similar to that of the model. Underlying social comparison processes and the
      mediational role of participants' liking of the model are considered.

PMID- 16594831
TI  - Free at last? Social dominance, loss aversion, and White and Black Americans'
      differing assessments of racial progress.
AB  - White Americans tend to believe that there has been greater progress toward
      racial equality than do Black Americans. The authors explain this difference by
      combining insights from prospect theory and social dominance theory. According to
      prospect theory, changes seem greater when framed as losses rather than gains.
      Social dominance theory predicts that White Americans tend to view increases in
      equality as losses, whereas Black Americans view them as gains. In Studies 1 and
      2, the authors experimentally tested whether groups judge the same change
      differently depending on whether it represents a loss or gain. In Studies 3-6,
      the authors used experimental methods to test whether White participants who
      frame equality-promoting changes as losses perceive greater progress toward
      racial equality. The authors discuss theoretical and political implications for
      progress toward a just society.

PMID- 16594832
TI  - Sex similarities and differences in preferences for short-term mates: what,
      whether, and why.
AB  - Are there sex differences in criteria for sexual relationships? The answer
      depends on what question a researcher asks. Data suggest that, whereas the sexes
      differ in whether they will enter short-term sexual relationships, they are more
      similar in what they prioritize in partners for such relationships. However,
      additional data and context of other findings and theory suggest different
      underlying reasons. In Studies 1 and 2, men and women were given varying "mate
      budgets" to design short-term mates and were asked whether they would actually
      mate with constructed partners. Study 3 used a mate-screening paradigm. Whereas
      women have been found to prioritize status in long-term mates, they instead (like
      men) prioritize physical attractiveness much like an economic necessity in short
      term mates. Both sexes also show evidence of favoring well-rounded long- and
      short-term mates when given the chance. In Studies 4 and 5, participants report
      reasons for having casual sex and what they find physically attractive. For
      women, results generally support a good genes account of short-term mating, as
      per strategic pluralism theory (S. W. Gangestad & J. A. Simpson, 2000).
      Discussion addresses broader theoretical implications for mate preference, and
      the link between method and theory in examining social decision processes.

PMID- 16594833
TI  - Factors underlying expectancies of success and achievement: the influential roles
      of need for cognition and general or specific self-concepts.
AB  - It has been assumed that task-specific self-concepts are more important than
      general self-concepts in determining expectancies of success and subsequent
      achievement. The authors argue here that the influence varies depending on need
      for cognition (NFC). Findings from Study 1 (N=104) showed that expectancies of
      success in an academic task could be predicted from specific self-concept for
      individuals with a high NFC and from general self-concept for individuals with a
      low NFC. In Study 2 (N=193), where cognitive load was manipulated, given a high
      cognitive load, only general self-concept was predictive of success expectancies,
      independent of NFC. In Study 3 (N=197), given a high relevance of correct
      expectancy ratings, only specific self-concept was predictive of expectancies and
      actual achievement, independent of NFC. In Studies 4 and 5, the results from
      Study 1 concerning the prediction of expectancies (as well as achievement)
      reappeared in a physical and a social domain.

PMID- 16594834
TI  - Personality and subjective well-being in orangutans (Pongo pygmaeus and Pongo
      abelii).
AB  - Orangutans (Pongo pygmaeus and Pongo abelii) are semisolitary apes and, among the
      great apes, the most distantly related to humans. Raters assessed 152 orangutans
      on 48 personality descriptors; 140 of these orangutans were also rated on a
      subjective well-being questionnaire. Principal-components analysis yielded 5
      reliable personality factors: Extraversion, Dominance, Neuroticism,
      Agreeableness, and Intellect. The authors found no factor analogous to human
      Conscientiousness. Among the orangutans rated on all 48 personality descriptors
      and the subjective well-being questionnaire, Extraversion, Agreeableness, and low
      Neuroticism were related to subjective well-being. These findings suggest that
      analogues of human, chimpanzee, and orangutan personality domains existed in a
      common ape ancestor.

PMID- 16594835
TI  - On the nature of intraindividual personality variability: reliability, validity,
      and associations with well-being.
AB  - Intraindividual personality variability is a construct that reflects the extent
      to which a person's self-reported personality changes over time or across social
      roles. Past studies have linked variability with important outcomes such as
      adjustment and well-being. However, existing variability measures conflate mean
      level variance with true change over time, and thus these past findings are
      questionable. Three studies were conducted to examine the psychometric properties
      of existing variability indexes and to develop a new index that does not suffer
      from the problem of conflated variance. This new index is reliable and valid and
      can predict actual changes in self-reports over time. However, once mean-level
      variance is removed, intraindividual variability is no longer related to well
      being.

PMID- 16594836
TI  - Finding "meaning" in psychology: a lay theories approach to self-regulation,
      social perception, and social development.
AB  - Much of psychology focuses on universal principles of thought and action.
      Although an extremely productive pursuit, this approach, by describing only the
      "average person," risks describing no one in particular. This article discusses
      an alternate approach that complements interests in universal principles with
      analyses of the unique psychological meaning that individuals find in their
      experiences and interactions. Rooted in research on social cognition, this
      approach examines how people's lay theories about the stability or malleability
      of human attributes alter the meaning they give to basic psychological processes
      such as self-regulation and social perception. Following a review of research on
      this lay theories perspective in the field of social psychology, the implications
      of analyzing psychological meaning for other fields such as developmental,
      cultural, and personality psychology are discussed.

PMID- 16594837
TI  - A new Big Five: fundamental principles for an integrative science of personality.
AB  - Despite impressive advances in recent years with respect to theory and research,
      personality psychology has yet to articulate clearly a comprehensive framework
      for understanding the whole person. In an effort to achieve that aim, the current
      article draws on the most promising empirical and theoretical trends in
      personality psychology today to articulate 5 big principles for an integrative
      science of the whole person. Personality is conceived as (a) an individual's
      unique variation on the general evolutionary design for human nature, expressed
      as a developing pattern of (b) dispositional traits, (c) characteristic
      adaptations, and (d) self-defining life narratives, complexly and differentially
      situated (e) in culture and social context. The 5 principles suggest a framework
      for integrating the Big Five model of personality traits with those self-defining
      features of psychological individuality constructed in response to situated
      social tasks and the human need to make meaning in culture.

PMID- 16594838
TI  - Research participants telling the truth about their lives: the ethics of asking
      and not asking about abuse.
AB  - Most discussions of the ethics of self-report research on abuse and interpersonal
      violence focus on the risks of asking participants about their experiences. An
      important element of the cost-benefit analysis--the costs of not asking about
      child abuse--has largely been ignored. Furthermore, little research has been
      conducted on the costs and benefits of child abuse research, leaving researchers
      to make decisions based on individual beliefs about such issues as the prevalence
      of abuse, the likelihood of disclosure, the effects of child abuse, and the
      ability of abuse survivors to give informed consent. The authors suggest that
      these beliefs tend to overemphasize survivors' vulnerability and ignore the costs
      of avoiding asking about abuse. In fact, these beliefs may reinforce societal
      avoidance of abuse and ultimately harm abuse survivors.

PMID- 16594839
TI  - The meeting of meditative disciplines and Western psychology: a mutually
      enriching dialogue.
AB  - Meditation is now one of the most enduring, widespread, and researched of all
      psychotherapeutic methods. However, to date the meeting of the meditative
      disciplines and Western psychology has been marred by significant
      misunderstandings and by an assimilative integration in which much of the
      richness and uniqueness of meditation and its psychologies and philosophies have
      been overlooked. Also overlooked have been their major implications for an
      understanding of such central psychological issues as cognition and attention,
      mental training and development, health and pathology, and psychological
      capacities and potentials. Investigating meditative traditions with greater
      cultural and conceptual sensitivity opens the possibility of a mutual enrichment
      of both the meditative traditions and Western psychology, with far-reaching
      benefits for both.

PMID- 16594840
TI  - Benjamin Franklin and shock-induced amnesia.
AB  - Shock-induced amnesia received considerable attention after Cerletti popularized
      electroconvulsive shock therapy in the late 1930s. Yet, often overlooked is the
      fact that Benjamin Franklin recognized that passing electricity through the head
      could affect memory for the traumatic event. Franklin described his findings on
      himself and others in several letters from the mid-1700s, 2 of which were
      published in his lifetime. What he observed was confirmed in 1783 by physician
      Jan Ingenhousz, who was one of his correspondents. Although Ingenhousz had lost
      his memory for his electrical accident and was confused immediately afterward, he
      felt strangely elated and unusually sharp the next morning. Hence, he called for
      clinical trials with patients with melancholia who were not responding to more
      conventional therapies. After Franklin received Ingenhousz's letter, he also
      called for clinical trials. Neither man, however, tied the possible new cure for
      melancholia to the memory loss--nor did the operators that began to treat some
      patients with melancholia successfully with cranial shocks. Only much later would
      the amnesia be thought to be associated with the cure.

PMID- 16594845
TI  - Clarifications with respect to psychology and phenomenology.

PMID- 16594846
TI  - A clarification of Heidegger's phenomenology.

PMID- 16594847
TI  - The ideology of logic in contemporary psychology.

PMID- 16594848
TI  - Phenomenology depends on human nature.

PMID- 16594849
TI  - Bias and obfuscation in Kendler's (2005) "Clarification".

PMID- 16594851
TI  - Colonial mentality: a review and recommendation for Filipino American psychology.
AB  - Colonial mentality is a term used widely by ethnic studies scholars and by the
      Filipino American community to refer to a form of internalized oppression among
      Filipinos and Filipino Americans. The authors propose that colonial mentality is
      a construct that is central to the understanding of the psychology of
      contemporary Filipino Americans. Drawing on larger scholarship from postcolonial
      studies and psychological research on oppression, the authors review the
      historical and sociological contexts in which to understand the significance of
      the colonial mentality concept for the Filipino American population. The authors
      also review the existing literature on colonial mentality and provide specific
      recommendations for incorporating this construct into research and practice with
      Filipino Americans. It is argued, through this illustrative example of colonial
      mentality among Filipino Americans, that examining the psychological impact of
      colonialism is a way to incorporate larger historical and sociological contextual
      variables into ethnic minority research and practice.

PMID- 16594852
TI  - Motivating minority older adults to exercise.
AB  - The purpose of this qualitative study was to explore with minority older adults
      their experience in the Senior Exercise Self-Efficacy Pilot Program (SESEP) and
      establish what aspects of the SESEP helped the participants engage in exercise
      and what decreased their willingness to exercise. A total of 148 older adults
      from 12 Senior Centers participated. The majority of the participants were
      African American (77%), and female (79%) and the average age was 72.9+/-8.0.
      Analysis of the semi-structured interviews revealed 36 codes which were
      categorized and reduced to 13 major themes. Eleven of these themes focused on
      factors that facilitated participation in exercise and two themes included
      factors that decreased willingness to participate in exercise. Findings support
      the use of the theory of self-efficacy to change behavior among minority older
      adults, and future research should focus on identifying culturally specific
      interventions that will strengthen these beliefs and thereby increase exercise
      behavior.

PMID- 16594853
TI  - Social contexts of drug offers among American Indian youth and their relationship
      to substance use: an exploratory study.
AB  - In this exploratory study the authors examined the social contexts of American
      Indian youths' encounters with drug offers and their relationship to substance
      use. Using an inventory of drug use-related problem situations developed
      specifically for American Indian youth, questionnaires were completed by 71
      American Indian youth at public middle schools in a Southwest metropolitan area.
      Regression analyses highlight the importance of situational and relational
      contexts in understanding substance use among the youth in this sample. Exposure
      to drug offers through parents, other adults, cousins, friends and other peers
      was associated with different types of substance use. Exposure through parents
      was particularly salient in predicting the drug use of female respondents. The
      study underscores the need for development of culturally grounded prevention
      programs in schools, reservations, and nonreservation communities.

PMID- 16594854
TI  - Effects of counseling Ashkenazi Jewish women about breast cancer risk.
AB  - The goal of this study was to determine whether genetic counseling or
      psychosocial group counseling provided to Ashkenazi women can reduce breast
      cancer worry, cancer risk perception, and interest in having genetic testing.
      Women (N=211) were randomized to receive individual genetic risk counseling, to
      receive a group psychosocial group counseling, or to serve as a control group.
      The authors found that both counseling methods reduced cancer worry, lowered
      perceptions of breast cancer risk, and decreased interest in having genetic
      testing. Counseling can help women gain a more accurate perception of their risk,
      expose them to the benefits and limitations of genetic testing, and reduce their
      worry about cancer.

PMID- 16594855
TI  - Achieving college student possible selves: navigating the space between
      commitment and achievement of long-term identity goals.
AB  - This study explores the possible-self construction and achievement process in
      students of color from low-income communities by investigating these processes in
      28 college students. Findings suggest that while parental encouragement of
      college aspirations may affect age at which the college student possible self is
      constructed and expectancy level, development of schematic possible selves is
      more crucial to achievement of possible-self goals. Furthermore, findings point
      out a need to include conceptual schemas, in addition to procedural schemas, as
      potential predictors of possible-self achievement.

PMID- 16594856
TI  - Low-income African American women's attempts to convince their main partner to
      use condoms.
AB  - In this cross-sectional study the authors examine condom use attempts and condom
      use among 305 high-risk, low-income African American women who reported having a
      main partner. Women who had recently attempted to convince their main partner to
      use condoms were almost 10 times more likely to have recently used condoms with
      their partner than women who had not made an attempt. Among the subsample of 116
      women who had recently made a condom use attempt with their main partner, having
      a history of childhood abuse and having one's main partner raise infidelity
      questions in response to the condom use attempt were negatively associated with
      recent condom use with this partner. Findings provide initial insights into the
      importance of women's condom use attempts, as well as subgroups of women who may
      encounter special challenges convincing their main partner to use condoms.

PMID- 16594857
TI  - Differences in family functioning in grandparent and parent-headed households in
      a clinical sample of drug-using African American adolescents.
AB  - Grandparents play a critical role in African American families, providing support
      and important leadership functions. Little is known, however, about family
      functioning in grandparent-headed households with a drug-using adolescent. Such
      knowledge is particularly salient for researchers and therapists who work with
      drug-using adolescents and their families. Using a clinical sample of
      convenience, analyses were conducted to identify similarities and differences in
      adolescent substance use and behavior problems, family relationships, and family
      social ecology relationships between African American grandparent-headed (n=12)
      and parent-headed (n=54) households. Results indicated that adolescents from the
      2 household types reported similar levels of problem behaviors, but that
      grandparents reported less delinquency with peers than did parents. Primary
      caregivers in grandparent-headed households reported less monitoring and
      supervision of peers and less within-family conflict. Implications for treatment
      are discussed.

PMID- 16594858
TI  - Using prayer in psychotherapy: applying Sue's differential to enhance culturally
      competent care.
AB  - In this article, the authors discuss the application of Sue's cultural competence
      differential of hypothesis testing, dynamic sizing, and cultural specific
      expertise as a model for considering cultural factors in the treatment of an
      African American family. Three cultural dimensions are highlighted: spirituality,
      womanism, and community exposure to trauma. Given the centrality of spirituality
      for this African American family, prayer is used to facilitate the therapeutic
      process. Discussion from a womanist perspective highlights the spiritual,
      communal, and personal dimensions that the aunt faces as an African American
      woman. Consideration of the community context and potential exposure to trauma
      and loss allows for a fuller appreciation of the psychosocial context of the
      nephew. Sue's differential guides the case discussion.

PMID- 16594859
TI  - Exemplary multicultural training in school psychology programs.
AB  - This study examined the characteristics of school psychology programs noted for
      training students from a multicultural perspective. The program characteristics
      and training environment at 17 programs were studied through semistructured
      interviews with faculty and students, and reviews of prospective student
      application materials for multicultural content. Findings suggest that students
      at all programs were exposed to minority clients during applied fieldwork, 94% of
      the programs required a diversity issues course, 59% of the programs specialized
      in training with specific minority group populations, 31% of the students and 25%
      of the faculty represented a racial-ethnic minority group member, and 24% of the
      faculty were bilingual. Most programs used multiple multicultural curriculum
      models and employed a wide variety of recruitment and retention strategies
      specifically aimed at minority students. Faculty and students characterized their
      overall university training environment as supportive of programmatic initiatives
      regarding diversity issues, yet several reported uneven experiences with
      implementation.

PMID- 16594860
TI  - Asian American families' collectivistic coping strategies in response to 9/11.
AB  - Our study investigated the use of individualistic and collectivistic coping
      strategies among Asian American family members of victims of the World Trade
      Center (WTC) attacks on September 11th, 2001. Interviews were conducted with 11
      Asian Americans who had lost a member of their family in the WTC attacks. Using
      the Discovery-Oriented Research analysis (Mahrer, 1988), results indicated that
      Asian Americans utilized the following collectivistic coping methods to deal with
      their losses: individualistic coping, familial coping, intracultural coping,
      relational universality, forbearance, fatalism/ spirituality, and indigenous
      healing methods. Additionally, our research found that cultural stigmata, privacy
      issues, and lack of culturally responsive counselors were factors in participants
      not utilizing available mental health services. Implications for culturally
      appropriate services, counseling, and research are discussed.

PMID- 16594861
TI  - Ethnic minorities' racial attitudes and contact experiences with white people.
AB  - In this article, the authors examine the relationship between ethnic minorities'
      racial attitudes and their intergroup contact experiences with White people. In
      Studies 1 and 2, the authors demonstrate that the more negative the racial
      attitudes held by ethnic minorities, the less positive their interactions are
      with White friends and roommates. With a daily report methodology, Study 2
      revealed that ethnic minorities' racial attitudes predicted the decline in the
      quality of their intergroup contact experiences over a 3-week period. In Study 3,
      the authors examined a possible mechanism underlying the relationship between
      racial attitudes and intergroup contact, as well as the influence of ethnic
      minorities' racial attitudes on White participants' experiences in intergroup
      contact settings. The authors discuss the findings in terms of the importance of
      examining ethnic minorities' attitudes in research on intergroup relations.

PMID- 16594864
TI  - Postgraduate medical placements in rural areas: their impact on the rural medical
      workforce.
AB  - INTRODUCTION: In 1988, the New South Wales (NSW) Department of Health developed
      the NSW Rural Resident Medical Officer Cadetship Program (Cadetship Program) to
      help overcome a junior doctor workforce shortage in rural hospitals. A second aim
      was to increase recruitment to the rural medical workforce on the basis that
      positive exposure to rural medicine increases the likelihood of choosing to
      practice in a rural location. The Cadetship Program offers bonded scholarships
      which provide financial support for residents of NSW studying medicine during the
      final 2 years of their medical degree. In return, cadets are contracted to
      complete 2 of their first 3 postgraduate years in the NSW rural hospital network.
      NSW Rural Doctors Network has managed the Cadetship Program for the NSW
      Department of Health since 1993, and carried out an evaluation in 2004. The
      purpose of this evaluation was to track the career choice and practice location
      of medical students entering the Cadetship Program before 1999, and to comment on
      the impact of the Program on the rural medical workforce in NSW to date, and its
      implications for the future workforce. METHODS: The career choice and practice
      locations of 107 medical students who received cadetships between 1989 and 1998
      were tracked. Students who did not graduate from medical school (n = 3) or who
      did not complete their rural service (13) were excluded from the analysis. Career
      choice was not available for a further nine former cadets and they were also
      excluded from the analysis. The NSW Rural Doctors Network was the major source of
      data on career choice and practice location due to its role in administering the
      Cadetship Program on behalf of the NSW Department of Health. Two brief
      questionnaires targeting specific groups of cadets were used to fill knowledge
      gaps about where cadets grew up, what vocational training they undertook, and
      where they were working in 2004. Where this information was not obtained from
      cadets first hand, it was sourced from the CD-ROM version of the Medical
      Directory of Australia. RESULTS: Forty-three percent of cadets entering the
      Program before 1999 were working in rural locations in 2004 (compared with 20.5%
      of medical practitioners nationally), 46% had attended primary school in a rural
      location and 44% chose to specialize in general practice. Career choice was the
      major determinant of practice location. Having a rural background did not appear
      to influence practice location; whereas, those specialising in general practice
      made up 70% of this cohort of cadets working in rural areas. All general practice
      trainees were in rural locations compared with only two of the 25 trainee
      specialists, which reflects the availability of accredited training places in
      rural Australia. CONCLUSIONS: The Cadetship Program, which ensures junior doctors
      work for 2 of their first 3 postgraduate years in a rural allocation centre, is
      an effective link between medical school and rural practice, particularly rural
      general practice. Providing vocational training opportunities in rural locations
      is central to this success, and needs to be considered in efforts to expand the
      rural specialist workforce, and in ensuring rural health capitalises on the
      increasing number of medical students moving through the education and training
      system in the next 4-10 years.

PMID- 16594865
TI  - Are we honestly studying malingering? A profile and comparison of simulated and
      suspected malingerers.
AB  - Malingering research typically uses analog simulation design or differential
      prevalence design among "real" patients. Both have been criticized for
      methodological limitations in external and internal validity, respectively.
      Samples of simulated malingerers were compared to suspected malingerers to
      examine generalizability of analog findings. Overall results support the use of
      simulation designs. Furthermore, it was demonstrated that stringent selection of
      suspected malingerers maintains internal validity of the differential prevalence
      design. A second focus, to determine if demographic matching of simulated
      malingerers is necessary, showed that matching on age and race is not necessary.

PMID- 16594867
TI  - Regulations governing the out-of-state practice of psychology: implications for
      forensic neuropsychologists.
AB  - Many states allow psychologists licensed in other jurisdictions to practice
      temporarily without obtaining a full license. However, both the restrictions of
      practice and the procedures required before practice is allowed vary extensively
      among states. This article examines the regulations of U.S. and Canadian
      territories governing temporary practice of nonresident psychologists. Current
      licensing laws were obtained from each state's respective psychological board or
      related Web sites from May to July 2004. Results highlighted vast regulatory and
      procedural differences for temporary practice among jurisdictions. Due to the
      degree of variability in each jurisdiction's regulations governing, caution must
      be taken so that psychologists comply with up-to-date guidelines before
      practicing outside of the regions in which they are licensed. The out-of-state
      psychologist must contact the appropriate state or provincial licensing board for
      guidelines and pertinent regulation.

PMID- 16594866
TI  - Factor analysis of the self-report Dysexecutive (DEX-S) Questionnaire.
AB  - The self-rating Dysexecutive Questionnaire (DEX-S) is a recently developed
      standardized self-report measure of behavioral difficulties associated with
      executive functioning such as impulsivity, inhibition control, monitoring, and
      planning. Few studies have examined its construct validity, particularly for its
      potential wider use across a variety of clinical and nonclinical populations.
      This study examines the factor structure of the DEX-S questionnaire using a
      sample of nonclinical (N = 293) and clinical (N = 49) participants. A series of
      factor analyses were evaluated to determine the best factor solution for this
      scale. This was found to be a 4-factor solution with factors best described as
      inhibition, intention, social regulation, and abstract problem solving. The first
      2 factors replicate factors from the 5-factor solutions found in previous studies
      that examined specific subpopulations. Although further research is needed to
      evaluate the factor structure within a range of subpopulations, this study
      supports the view that the DEX has the factor structure sufficient for its use in
      a wider context than only with neurological or head-injured patients. Overall, a
      4-factor solution is recommended as the most stable and parsimonious solution in
      the wider context.

PMID- 16594868
TI  - A comparison of MicroCog and the Wechsler Memory Scale (3rd ed.) in older adults.
AB  - In recent years, computerized assessment of cognitive functions such as memory
      has increased in popularity. Here we contrast the performance of 33 community
      dwelling older adults (mean age 71.2 years, SD = 7.62) on the computer-based
      MicroCog with the conventional Wechsler Memory Scale-3rd Edition (WMS-III).
      Participants were screened for possible depression using the Geriatric Depression
      Scale and completed both memory tests in counterbalanced order. WMS-III General
      Memory correlated moderately with both the MicroCog Memory index and the General
      Cognitive Functioning index. Correlations between the visual memory measures of
      the 2 tests were not statistically significant. Agreement between the tests on
      the classification of participants as lying within the average, below average, or
      above average ranges was fair at best. We conclude that the correspondence
      between the 2 measures is not sufficient to substitute 1 for the other for
      clinical decision making as to the memory functioning of older adults.

PMID- 16594869
TI  - Changes in frontal lobe activity with cognitive therapy for spider phobia.
AB  - Patients suffering from spider phobia were studied with measurement of regional
      cerebral blood flow (rCBF) when they were looking at a video recording of living
      spiders. Six patients were studied before and after cognitive psychotherapy with
      successful outcome in all cases. On each occasion rCBF was measured under 3
      conditions: during rest, during exposure to a video recording of neutral nature
      scenery, and finally while the patient watched a recording of living spiders. The
      patients who managed to control their emotional reactions without panicking
      during spider exposure before treatment showed an rCBF increase in prefrontal
      cortex, more pronounced in the right hemisphere. Following successful treatment,
      these patients showed an rCBF decrease in this region. In contrast, patients who
      reported panic during the initial spider exposure showed hypoactivity in the
      frontal cortex at that time, and then showed an increase in prefrontal rCBF in
      the spider challenge after cognitive therapy. The psychological improvement from
      cognitive therapy thus appears to be associated with activation of prefrontal
      cortex that varies closely with the demands for self-regulation of emotional
      reactivity.

PMID- 16594870
TI  - Are there sex differences in neuropsychological functions among patients with
      obsessive-compulsive disorder?
AB  - The purpose of this study was to examine whether men and women with obsessive
      compulsive disorder (OCD) demonstrate differences in neuropsychological
      functioning compared to healthy men and women. Participants were 56 consecutive
      patients (33 male, 23 female) and 40 healthy control participants (20 male, 20
      female) of comparable characteristics. Male and female patients had comparable
      symptom severity, illness duration, comorbidity, in- or out-patient status, and
      medication usage. An extensive neuropsychological test battery was administered
      including tests of general nonverbal intelligence, attention, verbal and
      nonverbal memory, and executive functions. Male and female OCD patients showed
      comparable neuropsychological performances on most cognitive domains. However, we
      found some evidence for cross-sex shifts in verbal fluency tasks (FAS and
      Category Alternation Test [CAT]), the reading component of the Stroop test, and
      the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span-Forward test.
      Post hoc analyses revealed that female patients showed reduced performance on
      these tests compared to healthy women, in the male-typical direction. Among OCD
      women only, there were significant negative correlations between OCD symptom
      severity and performance on the CAT and the reading Stroop. We conclude that sex
      does not seem to be a major determinant of neuropsychological function in OCD,
      but the observed cross-sex shifts on some tasks deserve further examination.

PMID- 16594871
TI  - fMRI of lexical-semantic priming in a chronic schizophrenia patient.
AB  - A neuropsychological hallmark of schizophrenia is a breakdown in semantic
      association networks that often impacts language and formal thought. Although
      computational models simulating this breakdown exist, studies have yet to
      investigate this phenomena using functional MRI (fMRI) coupled with an auditory
      lexical-decision semantic priming paradigm. Thus, this serves to functionally map
      brain activation to word pairs that differed with respect to a concept called
      "connectivity" in a patient with schizophrenia and a demographically matched
      control adult. Analyses revealed a striking difference with respect to the
      expected stepwise modulation of activation, with the control participant showing
      significantly greater areas of modulation than the participant with schizophrenia
      in regions classically implicated in language. Although the results are tentative
      because of the nature of this investigation (single-case study), they further
      support the characterization of schizophrenia as a breakdown in lexical-semantic
      association networks and represent one of the first fMRI studies of semantic
      priming in schizophrenia informed by a computer model.

PMID- 16594875
TI  - Reason, commonsense and imagination in the service of our shared humanity.

PMID- 16594876
TI  - In our own words: consumers' views on the reality of consumer participation in
      mental health care.
AB  - The opportunity for consumers to participate in all stages of mental health
      service delivery, including the planning of their individual care, is now clearly
      enshrined in Australian mental health policy. Published research which examines
      the extent to which this has been realised in practice is limited, and the
      paucity is even greater for research reflecting the views of the consumers
      themselves. This paper presents the findings of a qualitative study. In-depth
      interviews were undertaken with consumers of mental health services from two
      rural areas in Victoria to explore their views and opinions regarding their
      ability for genuine participation in the planning and delivery of their mental
      health care, and in particular on the role of nurses in facilitating this
      process. Data were analysed with the assistance of NVivo, using a content
      analysis approach. The main themes identified were: respect, encouragement,
      collaboration and systemic barriers. The findings suggest that consumer
      participants identify a number of barriers which limit their ability to
      participate effectively. The implications for the role of the nurse in
      facilitating genuine consumer participation are discussed.

PMID- 16594877
TI  - Consumer evaluation of a mental health liaison nurse service in the Emergency
      Department.
AB  - The mainstreaming of mental health services into the general healthcare system
      has added to the demands placed on Emergency Departments (EDs) in terms of the
      assessment, management and disposition of mental health related presentations.
      There is a growing body of research that highlights the difficulties encountered
      by consumers presenting to the ED with mental health concerns (Summers and
      Happell 2003). This paper describes a study undertaken to evaluate the Mental
      Health Liaison Nurse (MHLN) role in the ED of an inner city teaching hospital in
      Sydney Australia. The surveys, in a telephone interview conducted by a Consumer
      Consultant employed by the Area Mental Health Service (AMHS), provide mental
      health consumers with an opportunity for anonymous feedback on their experiences
      in the ED, their satisfaction with the MHLN role and follow-up arrangements in
      the community. Quantitative and qualitative data generated from the study are
      presented and discussed. The authors share their observations and experiences in
      conducting the study in order to further develop this avenue of service
      evaluation.

PMID- 16594878
TI  - Moving toward culturally sensitive services for Indigenous people: a non
      Indigenous mental health nursing perspective.
AB  - Indigenous psychiatric morbidity, whilst culturally different in presentation to
      white communities has been suggested to run at a mean prevalence rate of 13.5% of
      the major disorders found in non-Indigenous communities. This paper discusses the
      socio-political and cross cultural issues to do with mental health for Australian
      Indigenous from a non-Indigenous perspective. The paper is particularly concerned
      with the effects of racism on Indigenous mental health and how racism effectively
      limits Indigenous people from full participation in the pluralist mainstream.
      Racism has been seen to be a major contributor to mental illness. The scope of
      this paper addresses the issue of transforming mainstream culture as well as
      highlighting the need for protection, participation and collaborative involvement
      in mental health service delivery.

PMID- 16594879
TI  - A randomised controlled trial testing the impact of exercise on cognitive
      symptoms and disability of residents with dementia.
AB  - A randomized controlled trial was undertaken to measure effects of exercise on:
      1) the progression of cognitive symptoms related to dementia using the Clock-
      Drawing test Shulman et al. 1993); and 2) disability using the Revised Elderly
      Persons Disabilities Scale (REPDS; Fleming and Bowles 1993). Data was analysed
      from 75 nursing home residents with dementia who were randomly assigned to one
      experimental group and two control groups. Group 1 (control) received no
      intervention, Group 2 (control) received a social visit equivalent in duration
      and frequency as those undertaking the exercise program in the experimental
      group, Group 3. A specifically designed, frail aged appropriate, twelve week
      exercise program was undertaken by the those in the experimental group three
      times per week, each session lasted for thirty minutes. The findings from: 1) the
      clock drawing test showed that exercise may slow the rate of progression of the
      cognitive symptoms related to dementia; and 2) the REPDS showed that exercise
      slowed and reversed disability in some of the activities of daily living.

PMID- 16594880
TI  - Defining our scope of practice.

PMID- 16594881
TI  - Attitudes of registered psychiatric nurses towards patients diagnosed with
      borderline personality disorder.
AB  - Caring for patients with a diagnosis of Borderline Personality Disorder (BPD) has
      been identified as a problem area for mental health professionals with some
      studies suggesting that a diagnosis of BPD will influence the level and quality
      of interaction staff have with patients. It is inherent to psychiatric nursing
      that practitioners are able to establish rapport, develop trust and demonstrate
      empathy with consumers of mental health services. Despite the importance of this
      issue for psychiatric nurses and for consumers, the perceptions and attitudes of
      psychiatric nurses towards patients diagnosed with BPD have received almost no
      research attention. This paper describes findings from a study of attitudes held
      by 65 registered nurses employed in a psychiatric inpatient unit and psychiatric
      community service where individuals with a DSM-IV diagnosis of BPD received
      treatment. In particular, findings relating to Clinical Description, Emotional
      Reactions, Concerns and Management of patients with BPD are reported. Results
      show that a proportion of psychiatric nurses experience negative emotional
      reactions and attitudes toward people with BPD with the majority of nurses
      perceiving people with BPD as manipulative, almost one third reporting that
      patients with BPD made them angry and over one third either 'strongly disagreed'
      or 'disagreed' that they know how to care for people with BPD. Although
      psychiatric nurses face many challenges in providing care for patients with BPD,
      it is also of concern to the profession that one of the problems confronting
      people with BPD is the negative attitudes of those staff that care for them.
      Further research is necessary to identify appropriate service frameworks and
      clinical interventions that assist in more effective clinical management of
      clients of BPD.

PMID- 16594882
TI  - Workplace practices with mental health implications impacting on recruitment and
      retention of overseas nurses in the context of nursing shortages.
AB  - In response to nursing workforce shortages, health agencies in Australia and
      elsewhere have sought to meet the demand for nursing services by recruiting
      nurses internationally. While there is a major focus on recruitment, little
      attention is given to factors that could enhance retention of overseas qualified
      nurses. There are a host of factors reported in the literature that impact upon
      retention of overseas nurses in the workforce, including: impact of re-settlement
      experiences in the new country; discriminatory practices in accessing employment
      and negative experiences in the work place. For the benefit of long term
      retention of overseas nurse graduates in the workforce in Australia and globally,
      these experiences are major issues needing urgent attention. This discussion
      paper reviews the literature to explore the impact of aggression and
      discriminatory practices in nursing as evidence for nurses leaving the
      profession, and discusses the mental health implications and consequences of such
      practices relating to overseas nurse graduates.

PMID- 16594883
TI  - Best practice management strategies for mental health nurses during the clinical
      application of civil commitment: an overview.
AB  - AIM: The aim of this article is to outline best practice management strategies
      for nurses during the clinical application of civil commitment of mentally ill
      persons. METHOD: A thorough literature search on 'coercion' and 'civil
      commitment' was undertaken using MEDLINE, CINAHL and PSYCHINFO. Published and
      unpublished research undertaken by the authors in New Zealand on this topic was
      drawn upon. This research considered the use of civil commitment during admission
      to acute mental health services, acute forensic mental health services and
      community mental health services. RESULTS: The experience of coercion by service
      users coincides with the degree of restriction associated with the service they
      are involved in. Socio-demographic factors, clinical factors and the experience
      of coercive events have little bearing on the amount of coercion experienced.
      Rather it is the pattern of communication and the use of 'procedural justice'
      that has the potential to ameliorate the amount of perceived coercion.
      CONCLUSIONS: 'Procedural justice' aligns with the emphasis placed on the
      therapeutic relationship in mental health nursing and is an important
      consideration for nurses during the clinical application of civil commitment.

PMID- 16594884
TI  - Violence against psychiatric nurses: sensitive research as science and
      intervention.
AB  - Psychiatric nurses are frequent victims of workplace violence, much of which is
      perpetrated by patients. In a review of literature on prevalence, perpetrators,
      and impact of violence on psychiatric nurses, we note that workplace violence is
      a virtually normative experience for the nurse, rather than a rare occurrence.
      Verbal violence and sexual harassment, like physical violence, are common
      experiences; in contrast to physical violence, these are often initiated by co
      workers. The emotional impact of violence on psychiatric nurses is studied less
      often than frequency of exposure; we discuss hypotheses for this paucity of
      relevant research. Finally, we reflect on the implications of current research,
      concluding with recommendations for future research on violence against
      psychiatric nurses. In particular, we elaborate on the role of violence research
      in the healthcare setting as "sensitive research"--a research process that in
      itself may have both direct and indirect beneficial effects for the nursing
      profession.

PMID- 16594885
TI  - Community-based postpartum depression screening within the first month after
      delivery.
AB  - Postpartum depression (PPD) is a common childbirth complication. Approximately
      500,000 women in the United States each year experience PPD, and about half of
      these women are not evaluated or treated appropriately. Although available
      screening measures can detect PPD symptoms, screening is not yet standard
      practice. This article presents outcomes from PPD screening of a community-based
      sample of 1,071 women at 2-4 weeks after delivery. Overall PPD symptom prevalence
      was 19.7%. Detection of PPD could be increased significantly by adapting research
      based screening approaches to clinical care.

PMID- 16594886
TI  - The use of psychotropic medications with breastfeeding women: applying the
      available evidence.
AB  - Breastfeeding women may be prescribed a psychotropic medication to treat a pre
      existing illness such as bipolar disorder or schizophrenia, or to treat an
      illness that develops as a direct result of pregnancy and childbirth, such as
      depression. Mental health nurses are often not aware that many psychotropic
      medications are considered relatively safe for the infant as well as the
      breastfeeding woman. This paper provides the clinician with an overview of the
      major psychotropic medications for breastfeeding women and outlines their
      potential impact on the infant. Guidelines for the use of these medications are
      also provided for mental health nurses based on the available evidence.

PMID- 16594887
TI  - Dementia related aggression in the acute sector: is a Code Black really the
      answer?
AB  - OBJECTIVE: This paper presents the findings of one facet of a larger study that
      explored the management of people with dementia as inpatients of acute care. The
      aim of the study is to provide a comprehensive multiprofessional view of the
      experience of providing care to people with dementia in an acute setting. DESIGN:
      Descriptive exploratory study. SETTING: Three acute care hospitals in South
      Australia. PARTICIPANTS: 25 health professionals who regularly provided care to
      people admitted to hospital with concurrent dementia. RESULTS: The information
      gathered provided a rich understanding of the frailty, dependency and
      unpredictable behaviour of people living with some form of dementia and how that
      creates tensions in a place that is environmentally, culturally and resourcefully
      bereft of what is required for truly effective care. CONCLUSION: The study showed
      that people with dementia are increasingly being admitted to hospital across
      almost every specialty and that many staff are ill prepared for meeting their
      needs. The heavily medically dominated environment of an acute care system lends
      itself to increased confusion and agitation in these people that may rapidly
      escalate to aggression and violence. Due to various shortfalls in that system,
      staff will often resort to restraint in managing disruptive behaviour--which is
      not in the best interest of the patient or the health care system. The way
      forward is to foster a multifactorial approach to a 'dementia friendly' system of
      care supported by education.

PMID- 16594888
TI  - Reflections on mental health nursing education.

PMID- 16594889
TI  - Managing the 'unmanageable': training staff in the use of dialectical behaviour
      therapy for borderline personality disorder.
AB  - Ninety-four staff from a regionally based mental health service and associated
      health and human services completed a two-day workshop introducing dialectical
      behaviour therapy, with a smaller number also undertaking advanced training.
      Survey and focus group data were collected on participants' demographics,
      attitudes, knowledge and experience of working with persons with this disorder,
      prior to and at one-month and six-months following completion of the introductory
      workshops. Quantitative and qualitative findings indicated that involvement in
      the training program was a positive experience for the majority of participants,
      with knowledge regarding detection and treatment and staff attitudes toward
      consumers being improved following exposure to the principles and practice of
      dialectical behaviour therapy. Discourse analysis of the focus group interview
      data pre- and post-training indicated a significant shift in the meanings staff
      associate with borderline personality disorder, with a pervasive therapeutic
      pessimism being displaced by more optimistic understandings and outlooks.
      Improved therapeutic outlook is likely to have positive implications for staff
      engagement with service users with borderline personality disorder. While this
      article provides a brief overview of the findings of the survey, the main purpose
      is to report the findings of the focus group interviews.

PMID- 16594890
TI  - Creating supportive environments for mental health promotion in the workplace.
AB  - Work is both an important resource for mental health, yet it also presents risk
      factors for mental illness. Consequently, the workplace has been identified as a
      potential setting for both mental health promotion and mental illness prevention.
      In the workplace various programs have been implemented which address risk
      factors for mental illness eg. stress management programs or the introduction of
      anti-bullying policies. However, few programs have been developed to address
      mental health promotion. It seems that the potential of mental health promotion
      is not fully utilised in this setting, nor are programs and initiatives to
      promote mental health as prolific as those in the physical health area.
      Furthermore, despite the introduction of legislation and workplace policies,
      structural changes have been unsuccessful in bringing about environmental
      modification which fosters mental well-being. This article explores explanations
      for this and makes recommendations utilising primary health care as an approach
      by which this situation can be redressed.

PMID- 16594891
TI  - Mental health nursing in New Zealand primary health care.
AB  - International literature and New Zealand health policy is giving increased
      emphasis to the role of the primary health care sector in responding to mental
      health issues. These issues include the need for health promotion, improved
      detection and treatment of mild to moderate mental illness, and provision of
      mental health care to some of those with severe mental illness who traditionally
      receive care in secondary services. These developments challenge specialist
      mental health nurses to develop new roles which extend their practice into
      primary health care. In some parts of New Zealand this process has been under way
      for some time in the form of shared care projects. However developments currently
      are ad hoc. There is room for considerable development of specialist mental
      health nursing roles, including roles for nurse practitioners in primary mental
      health care.

PMID- 16594892
TI  - Educating mental health nurses in clinical settings: tackling the challenge.

PMID- 16594894
TI  - Advances in contemporary mental health nursing: a continuous process.

PMID- 16594895
TI  - In vitro reconstitution of the GTPase-associated centre of the archaebacterial
      ribosome: the functional features observed in a hybrid form with Escherichia coli
      50S subunits.
AB  - We cloned the genes encoding the ribosomal proteins Ph (Pyrococcus horikoshii)
      P0, Ph-L12 and Ph-L11, which constitute the GTPase-associated centre of the
      archaebacterium Pyrococcus horikoshii. These proteins are homologues of the
      eukaryotic P0, P1/P2 and eL12 proteins, and correspond to Escherichia coli L10,
      L7/L12 and L11 proteins respectively. The proteins and the truncation mutants of
      Ph-P0 were overexpressed in E. coli cells and used for in vitro assembly on to
      the conserved domain around position 1070 of 23S rRNA (E. coli numbering). Ph-L12
      tightly associated as a homodimer and bound to the C-terminal half of Ph-P0. The
      Ph-P0.Ph-L12 complex and Ph-L11 bound to the 1070 rRNA fragments from the three
      biological kingdoms in the same manner as the equivalent proteins of eukaryotic
      and eubacterial ribosomes. The Ph-P0.Ph-L12 complex and Ph-L11 could replace
      L10.L7/L12 and L11 respectively, on the E. coli 50S subunit in vitro. The
      resultant hybrid ribosome was accessible for eukaryotic, as well as
      archaebacterial elongation factors, but not for prokaryotic elongation factors.
      The GTPase and polyphenylalanine-synthetic activity that is dependent on
      eukaryotic elongation factors was comparable with that of the hybrid ribosomes
      carrying the eukaryotic ribosomal proteins. The results suggest that the
      archaebacterial proteins, including the Ph-L12 homodimer, are functionally
      accessible to eukaryotic translation factors.

PMID- 16594898
TI  - Hypothesis: a biological role for germline transcription in the mechanism of
      V(D)J recombination--implications for initiation of allelic exclusion.
AB  - The sequences that encode the antigen-binding sites of IgH and IgL chains -
      variable (V), diversity (D, H chain loci only) and joining (J) sequences - are
      configured as separate DNA segments at the germline level. Expression of an Ig
      molecule requires V(D)J assembly. Productive V(D)J recombination is monoallelic.
      How rearrangement is initiated differentially at maternal and paternal alleles is
      unclear. The products of recombination activating gene (RAG)1 and RAG2 mediate
      rearrangement by cleaving the DNA between an unrearranged gene segment and
      adjacent recombination signal sequences (RSS). It is proposed that supercoiling
      generated during germline transcription at Ig loci (which occurs concomitantly
      with rearrangement) is required at RSS for RAG1/2 recognition. Rearrangement
      might hence initiate sequentially at maternal and paternal alleles where
      deregulated germline transcription causes RAG1/2 recognition of RSS to become
      stochastic.

PMID- 16594897
TI  - Increased IL-4 production and attenuated proliferative and pro-inflammatory
      responses of splenocytes from wild-caught rats (Rattus norvegicus).
AB  - Wild animals, unlike their laboratory counterparts, live amidst an abundance of
      pathogens and parasites. The presence of such immune stimulation from the time of
      birth likely has a profound effect on the development and stasis of the immune
      system. To probe potential differences between the immune systems of wild and
      laboratory animals, the response to mitogen (Con A) of splenocytes from wild rats
      was evaluated in vitro and compared with results from lab-rat-derived
      splenocytes. Although the response to mitogen is ubiquitous in splenocytes from
      laboratory animals regardless of strain or even species, splenocytes derived from
      wild rats were unresponsive to mitogen as judged by upregulation of activation
      markers and proliferation. Further, splenocytes from wild rats produced almost 10
      fold less IL-2 and TNF-alpha in response to mitogen than did splenocytes from
      laboratory rats. In addition, mitogen stimulation resulted in an almost 100-fold
      greater production of IL-4 in wild-rat-derived splenocytes than in lab-rat
      derived splenocytes. Perhaps surprisingly, these differences were observed in the
      absence of differences between wild and laboratory animals in the ratio of
      CD4+/CD8+ T cells or in the relative numbers of T cells, B cells and monocytes in
      the splenocyte population. These observations may have substantial implications
      for the hygiene hypothesis and provide considerable insight into the roles played
      by the environment during immune system development and modulation.

PMID- 16594896
TI  - HIV protease cleaves poly(A)-binding protein.
AB  - The PABP [poly(A)-binding protein] is able to interact with the 3' poly(A) tail
      of eukaryotic mRNA, promoting its translation. Cleavage of PABP by viral
      proteases encoded by several picornaviruses and caliciviruses plays a role in the
      abrogation of cellular protein synthesis. We report that infection of MT-2 cells
      with HIV-1 leads to efficient proteolysis of PABP. Analysis of PABP integrity was
      carried out in BHK-21 (baby-hamster kidney) and COS-7 cells upon individual
      expression of the protease from several members of the Retroviridae family, e.g.
      MoMLV (Moloney murine leukaemia virus), MMTV (mouse mammary tumour virus), HTLV-I
      (human T-cell leukaemia virus type I), SIV (simian immunodeficiency virus), HIV-1
      and HIV-2. Moreover, protease activity against PABP was tested in a HeLa-cell
      free system. Only MMTV, HIV-1 and HIV-2 proteases were able to cleave PABP in the
      absence of other viral proteins. Purified HIV-1 and HIV-2 proteases cleave PABP1
      directly at positions 237 and 477, separating the two first RNA-recognition
      motifs from the C-terminal domain of PABP. An additional cleavage site located at
      position 410 was detected for HIV-2 protease. These findings indicate that some
      retroviruses may share with picornaviruses and caliciviruses the capacity to
      proteolyse PABP.

PMID- 16594899
TI  - Inhibition of nuclear factor-kappaB activation is essential for membrane
      associated TNF-alpha-induced apoptosis in HL-60 cells.
AB  - The killing of tumour cells that are resistant to soluble TNF-alpha (sTNF-alpha)
      by the membrane-bound form of TNF-alpha (mTNF-alpha) suggests that different
      intracellular signalling pathways are involved. We found that mTNF-alpha induced
      apoptosis in HL-60 cells and failed to cause degradation of inhibitor of kappa B
      alpha (IkappaB-alpha) and translocation and activation of nuclear factor kappa B
      (NF-kappaB), whereas sTNF-alpha failed to induce apoptosis, but lowered
      cytoplasmic inhibitor of kappa B alpha, induced translocation of NF-kappaB to the
      nucleus and experimentally increased activity of the regulated luciferase.
      Furthermore, mTNF-alpha upregulated the expression of TNF receptor associated
      factor (TRAF) 1 and failed to induce TRAF1 and TRAF2 membrane translocation, but
      led to cytoplasmic colocalization. In contrast, sTNF-alpha stimulated the
      expression of TRAF1 and TRAF2, recruiting both molecules onto the cell membrane
      poststimulation. These results suggest that the increased susceptibility of HL-60
      cells to mTNF-alpha may be due to the failure of TRAF2 membrane translocation
      caused by the upregulation of TRAF1 expression and formation of a TRAF1/TRAF2
      complex in the cytoplasm, thereby inhibiting NF-kappaB activation and inducing
      apoptosis.

PMID- 16594900
TI  - Importance of carbohydrate in the interaction of Tamm-Horsfall protein with
      complement 1q and inhibition of classical complement activation.
AB  - Tamm-Horsfall protein (THP) binds strongly to complement 1q (C1q), a key
      component of the classical complement pathway. The goals of this study were to
      determine whether THP altered the activation of the classical complement pathway
      and whether the carbohydrate portion of THP was involved in this glycoprotein's
      binding to C1q and alteration of complement activation. The ability of THP to
      prevent complement activation in diluted serum or plasma incubated at 37 degrees
      C was assessed using both a haemolytic assay with antibody-sensitized sheep RBC
      and a C4d ELISA. Both these methods showed that THP inhibited activation of the
      classical complement pathway in a dose-dependent manner. Glycosidases were used
      to remove most of the carbohydrate from THP. This partially deglycosylated THP
      bound human IgG with a higher affinity (KD1 = 1.4 nmol/L; KD2 = 0.31 micromol/L)
      than did intact THP (KD1 = 33.4 nmol/L; KD2 = 31.0 micromol/L). An ELISA showed
      that removal of carbohydrate from THP reduced, but did not eliminate, the ability
      of this protein to inhibit binding of C1q to intact THP. Haemolysis assays using
      antibody-sensitized sheep RBC showed that removal of THP carbohydrate eliminated
      the ability of THP to protect against complement activation. In conclusion, THP
      inhibited the activation of the classical complement pathway that occurred in
      diluted serum or plasma. The carbohydrate moieties of THP appeared to be
      important in this inhibitory activity.

PMID- 16594901
TI  - Introduction: mechanotransduction and translational medicine workshop.

PMID- 16594902
TI  - Mechanotransduction and the glycocalyx.
AB  - Endothelial cells (ECs) line all blood vessel walls and are exposed to the
      mechanical forces of blood flow which modulate their function and play a role in
      vascular regulation, remodelling and disease. The principal mechanical forces
      sensed by ECs are the shear stress of flowing blood on their apical surface, and
      the circumferential stress resisting blood pressure, which induces stretch in the
      cell body. 'Mechanotransduction' refers to the mechanisms by which these forces
      are transduced into biomolecular responses of the cells. Given the importance of
      endothelial mechanotransduction in cardiovascular physiology and pathology,
      numerous research efforts have been dedicated to identifying the mechanosensory
      component(s) of ECs. This review focuses on mechanotransduction of shear stress
      by ECs and considers the evidence in support of the surface glycocalyx acting as
      a mechanotransducer.

PMID- 16594903
TI  - Endothelial mechanotransduction, nitric oxide and vascular inflammation.
AB  - Numerous aspects of vascular homeostasis are modulated by nitric oxide and
      reactive oxygen species (ROS). The production of these is dramatically influenced
      by mechanical forces imposed on the endothelium and vascular smooth muscle. In
      this review, we will discuss the effects of mechanical forces on the expression
      of the endothelial cell nitric oxide synthase, production of ROS and modulation
      of endothelial cell glutathione. We will also review data that exercise training
      in vivo has a similar effect as laminar shear on endothelial function and discuss
      the clinical relevance of these basic findings.

PMID- 16594904
TI  - Mechanotransduction and the homeostatic significance of maintaining blood
      viscosity in hypotension, hypertension and haemorrhage.
AB  - The increase of plasma and blood viscosity is usually associated with
      pathological conditions; however, elevation of both parameters often results in
      increased perfusion and the lowering of peripheral vascular resistance. In
      extreme haemodilution, blood viscosity is too low and insufficient to maintain
      functional capillary density, a problem that in experimental studies is shown to
      be corrected by increasing plasma viscosity up to 2.2 cP. This effect is mediated
      by mechanotransduction-induced nitric oxide (NO) production via shear stress in
      the endothelium as shown by microelectrode perivascular measurements of NO
      concentration. Moderate elevations of blood viscosity by increasing haematocrit (
      approximately 10%) result in comparable reductions of blood pressure and
      peripheral vascular resistance, an effect also NO-mediated as it is absent after
      Nomega-nitro-L-arginine methyl ester treatment and in endothelial nitric oxide
      synthase-deficient mice. These findings show that the rheological properties of
      plasma affect vessel diameter in the microcirculation leading to counterintuitive
      responses to the changes in blood and plasma viscosity. Application of these
      findings to haemorrhagic shock resuscitation leads to the concept of hyperosmotic
      hyperviscous resuscitation as a modality for maintaining the recovery of
      microvascular function.

PMID- 16594905
TI  - Platelet endothelial cell adhesion molecule-1 and mechanotransduction in vascular
      endothelial cells.
AB  - Endothelial cells are known to respond to mechanical forces such as fluid shear
      stress and cyclic stretch, but elucidating the mechanism for mechanosensing has
      been difficult. Experimental data indicate that there are probably several
      sensing mechanisms. We have recently proposed a novel mechanoresponse mechanism
      that involves platelet endothelial cell adhesion molecule-1 (PECAM-1). When
      endothelial cells are stimulated by fluid shear stress, PECAM-1 is tyrosine
      phosphorylated and activates the extracellular signal-regulated kinase 1 and 2
      (ERK1/2) signalling cascade. The same signalling events occurred when we applied
      pulling force directly on PECAM-1 on the endothelial cell surface using magnetic
      beads coated with antibodies against the external domain of PECAM-1. These
      results appear to indicate that PECAM-1 is a mechanotransduction molecule. To our
      knowledge, this is the first mammalian molecule that is shown to respond to
      mechanical force directly exerted to it.

PMID- 16594906
TI  - Molecular mechanisms of the vascular responses to haemodynamic forces.
AB  - Blood vessels are permanently subjected to mechanical forces in the form of
      stretch, encompassing cyclic mechanical strain due to the pulsatile nature of
      blood flow and shear stress. Significant variations in mechanical forces, of
      physiological or physiopathological nature, occur in vivo. These are accompanied
      by phenotypical modulation of smooth muscle cells and endothelial cells,
      producing structural modifications of the arterial wall. In all the cases,
      vascular remodelling can be allotted to a modification of the tensional strain or
      shear, and underlie a trend to reestablish baseline mechanical conditions.
      Vascular cells are equipped with numerous receptors that allow them to detect and
      respond to the mechanical forces generated by pressure and shear stress. The
      cytoskeleton and other structural components have an established role in
      mechanotransduction, being able to transmit and modulate tension within the cell
      via focal adhesion sites, integrins, cellular junctions and the extracellular
      matrix. Mechanical forces also initiate complex signal transduction cascades,
      including nuclear factor-kappaB and mitogen-activated protein kinase pathways,
      leading to functional changes within the cell.

PMID- 16594907
TI  - Vasculoprotective properties of the endothelial glycocalyx: effects of fluid
      shear stress.
AB  - The endothelial glycocalyx exerts a wide array of vasculoprotective effects via
      inhibition of coagulation and leucocyte adhesion, by contributing to the vascular
      permeability barrier and by mediating shear stress-induced NO release. In this
      review, we will focus on the relationship between fluid shear stress and the
      endothelial glycocalyx. We will address the hypothesis that modulation of
      glycocalyx synthesis by fluid shear stress may contribute to thinner
      glycocalyces, and therefore more vulnerable endothelium, at lesion-prone sites of
      arterial bifurcations. Finally, we will discuss the effects of known atherogenic
      stimuli such as hyperglycaemia on whole body glycocalyx volume in humans and its
      effect on endothelial function.

PMID- 16594908
TI  - Genetically determined apo B levels and peak LDL density predict angiographic
      response to intensive lipid-lowering therapy.
AB  - OBJECTIVE: Lipid-lowering therapy (LL-Rx) reduces coronary artery disease (CAD)
      but the response varies amongst individuals. We investigated the contribution of
      three genetic forms of dyslipidaemia characterized by elevated plasma apo B,
      familial hypercholesterolaemia (FH), familial combined hyperlipidaemia (FCHL),
      and elevated Lp(a), to the angiographic response with LL-Rx. METHODS AND RESULTS:
      Fifty-one men, with premature CAD and elevated plasma apo B, were selected in
      whom a genetic diagnosis was based on lipid phenotypes in relatives. Subjects
      received conventional (diet +/- colestipol) or intensive LL-Rx (niacin or
      lovastatin plus colestipol). Clinical parameters and CAD severity were measured
      before and after 2 years of treatment. Twenty-seven patients had FCHL, 12 FH and
      12 elevated Lp(a). Regression of coronary stenosis was dependent on the effect of
      therapy (P < 0.001), genetic form of dyslipidaemia (P = 0.004) and the
      interaction between the two variables (P = 0.02). Significant regression of
      coronary stenosis occurred only in FCHL and Lp(a) (P = 0.03, vs. control groups);
      CAD progression was only slowed in FH. CONCLUSIONS: Three genetic forms of
      dyslipidaemia were associated with different angiographic outcomes during
      intensive LL-Rx. Different forms of dyslipidaemia therefore may require different
      lipid-lowering strategy. Patients with FH and buoyant LDL require more aggressive
      reduction of LDL cholesterol whilst those with either FCHL or elevated Lp(a) with
      dense LDL need LDL cholesterol reduction as well as therapies aimed at reduction
      of the small, dense LDL particles.

PMID- 16594909
TI  - Rising incidence and persistently high mortality of hospitalized pneumonia: a 10
      year population-based study in Denmark.
AB  - BACKGROUND: Little is known about temporal trends in the incidence and mortality
      of pneumonia in the general population. METHODS: We conducted a population-based
      cohort study in three Danish counties (population 1.4 million) to examine changes
      in the incidence and 30- and 90-day mortality associated with hospitalized
      pneumonia between 1994 and 2004. All adults hospitalized with a first-time
      diagnosis of pneumonia (n = 41 793) were identified in hospital discharge
      registries and followed for mortality through the Danish Civil Registry System.
      We determined age-standardized incidence rates and adjusted mortality rates
      associated with calendar year, gender, age and comorbidity. RESULTS: Between 1994
      and 2003, the incidence of hospitalized pneumonia amongst adults increased from
      288 per 100 000 person-years to 442 per 100 000 person-years, equivalent to an
      age-standardized incidence rate ratio of 1.50. The cumulative mortality within 30
      and 90 days of admission was 15.2% and 21.9%, respectively, ranging from a 90-day
      mortality of 2.5% in patients aged 15-39 years to 34.7% in those aged 80 and
      over. Advanced age was the most important poor prognostic factor, followed by a
      high comorbidity score and male gender. The adjusted mortality rate ratios
      amongst patients with hospitalized pneumonia in 1999-2004, when compared with
      1994-1998, were 0.89 (95% CI 0.85-0.94) after 30 days and 0.91 (95% CI 0.88-0.95)
      after 90 days. CONCLUSIONS: The incidence of hospitalized pneumonia in Denmark
      has increased considerably during the last 10 years and, combined with
      persistently high mortality rates, is of clinical and public health concern.

PMID- 16594910
TI  - Coronary heart disease risks in first- and second-generation immigrants in
      Sweden: a follow-up study.
AB  - OBJECTIVES: To analyse whether there is an association between country of birth
      in first-generation immigrants and first hospitalization for or death from
      coronary heart disease (CHD) and to analyse whether this association remains in
      second-generation immigrants. DESIGN: In this follow-up study, the MigMed
      database at the Karolinska Institute, Stockholm, was used to identify all
      hospital diagnoses of and deaths from incident CHD in first- and second
      generation immigrants in Sweden between 1 January 1987 and 31 December 2001.
      Incidence ratios standardized by age, geographical region and socio-economic
      status were estimated by sex in first- and second-generation immigrants; the
      reference group was Swedish-born people whose parents were both born in Sweden.
      SUBJECTS: The total Swedish population aged 25-69 years. RESULTS: First
      generation immigrants from Finland, central European countries, other eastern
      European countries and Turkey had higher rates of CHD than men or women in the
      reference group. First-generation immigrant women born in southern Europe, other
      western European countries and Baltic countries had lower CHD risks than the
      reference group. Sons of both male and female first-generation immigrants showed
      CHD risks similar to or slightly higher than those of their parents. Amongst
      second-generation women, only subjects with Finnish fathers or mothers had higher
      risks of developing CHD than the reference. CONCLUSIONS: Increased risks of CHD
      found in some first-generation immigrant groups often persist in second
      generation immigrant men. Healthcare professionals and policy makers should take
      this into account when designing and undertaking measures to prevent CHD.

PMID- 16594911
TI  - Thymic carcinoid in multiple endocrine neoplasia 1: genotype-phenotype
      correlation and prevention.
AB  - Thymic carcinoid is a rare multiple endocrine neoplasia type 1 (MEN1)-associated
      tumour that is a major cause of death in MEN1 patients. Here, we describe a
      previously unreported MEN1 family in which two siblings presented with malignant
      thymic carcinoids. All six siblings share a novel nonsense mutation Q395X on exon
      8 of the MEN1 gene. The index patient developed a thymic carcinoid despite an
      earlier prophylactic transcervical thymectomy, and one other sibling had an
      incidental malignant thymic carcinoid discovered following prophylactic
      thymectomy, both cases demonstrating the weakness and strength of this surgical
      approach. We then review the spectrum of germline MEN1 mutations associated with
      thymic carcinoids to evaluate the possibility of a genotype-phenotype
      correlation. In the 22 separate MEN1 families with thymic carcinoids, all but two
      (91%) have mutations coding for a truncated protein. There is clearly a high
      prevalence of truncating mutations in MEN1-related thymic carcinoids although
      when compared with the prevalence of truncating mutations in all reported MEN1
      mutations, it is not statistically significant (P = 0.39). Further studies are
      warranted to evaluate pathways of tumorigenesis of thymic carcinoids with regard
      to loss of function of menin.

PMID- 16594914
TI  - Microscopes, microbes and molecules: evolution of our understanding of the cause
      and natural history of the precursor lesions of squamous lower genital tract
      neoplasia.

PMID- 16594915
TI  - Fetal pulse oximetry and wavelet analysis of the fetal heart rate in the
      evaluation of abnormal cardiotocography tracings.
AB  - AIM: Previous studies indicate that the addition of wavelet analysis of the fetal
      pulse oximetry tracings (FSPO2) and fetal heart rate (FHR) variability to
      cardiotocography (CTG), for intrapartum fetal monitoring, provides useful
      information on the fetal response to hypoxia. We applied the new procedure in non
      reassuring CTG patterns, in which cesarean section was performed, and tested its
      accuracy in the diagnosis of the intrapartum fetal compromise. METHODS: At the
      'Aretaieion' University Hospital labor ward, 318 women with term fetuses in the
      cephalic presentation entered the trial during labor. They all were monitored
      with external CTG and fetal pulse oximetry. In the cases that cesarean section
      was applied, because of abnormal CTG tracings, we applied a method based on the
      multiresolution wavelet analysis and a self-organized map neural network on the
      first and second stage of labor. The main outcome parameter was the rate of cord
      metabolic acidosis at birth (pH < 7.05). Secondary outcomes included Apgar scores
      at 5 min, fetal transmission to neonatal intensive care unit (NICU) and neonatal
      encephalopathy. RESULTS: Fifty out of 318 cases delivered operatively because of
      abnormal CTG patterns (rate 15.72%). In 30 cases, cord pH was >7.05, while in 11
      Apgar scores at 5 min were <7, while none of those neonates were transferred to
      NICU. In the rest 20 cases cord pH was <7.05; in all of these cases Apgar scores
      at 5 min were <7, while four neonates were transferred to NICU. In one of them,
      neonatal encephalopathy was diagnosed. After the offline application of wavelet
      analysis and neural networks to the pulse oximetry and FHR variability readings
      of the 50 cases, statistics calculated that the system showed a sensitivity of
      85% and a specificity of 93%, while false negative and false positive rates were
      15% and 7%, respectively. CONCLUSION: Computerized FHR and FSPO2 monitoring shows
      an excellent efficacy and reliability in interpreting non-reassuring FHR
      recordings.

PMID- 16594916
TI  - Basic study of healing of injuries to the myometrium and amniotic membrane using
      photocrosslinkable chitosan.
AB  - AIM: We performed in vivo and in vitro adhesion experiments on the use of
      photocrosslinkable chitosan (PC) for healing of the myometrium and the amniotic
      membrane to test its usefulness in the perinatal field. METHODS: To determine the
      adhesion conditions of PC in the healing of the myometrium and amniotic membrane,
      we applied two concentrations (30 and 50 mg/mL) of PC to the postpartum amniotic
      membrane, and radiated it with ultraviolet (UV) light for 10, 20, 30 or 60 s.
      Next, we created incisions of three sizes (pinhole, 5 mm and 10 mm), and
      performed PC adhesion followed by pressure application experiments. Subsequently,
      we laparotomized 12-day-pregnant rats under anesthesia, created a 5-mm incision,
      applied PC and closed the abdomen. We removed the uterus at 20 days of pregnancy,
      and histologically examined the site of PC application. RESULTS: The optimal
      adhesion conditions of PC were 50 mg/mL, and the optimal time of UV irradiation
      was 30 s or longer. In pressure application experiments, the bonding strength of
      PC was so high that even 10-mm incisions withstood a mean pressure of 92 mmH2O.
      The bonding strength of PC was significantly higher than that of fibrin glue that
      was tested in parallel. Histological examination of the rat myometrium showed a
      mild foreign body reaction with no inflammatory findings, confirming the
      usefulness of PC. CONCLUSIONS: PC is a wound-healing drug, an improvement on the
      naturally occurring polysaccharide chitosan, and is safer and has a higher
      bonding strength than biological adhesives including fibrin, making it promising
      for fetal surgical and perinatal applications.

PMID- 16594917
TI  - Inhibition of matrix metalloproteinase-2 secretion and invasion by human ovarian
      cancer cell line SK-OV-3 with lysine, proline, arginine, ascorbic acid and green
      tea extract.
AB  - AIMS: Based on the poor prognosis associated with ovarian cancer and reported
      anticancer properties of specific nutrients, we investigated the effect of a
      nutrient mixture (NM) containing lysine, proline, arginine, ascorbic acid and
      epigallocatechin gallate on human ovarian cancer cells SK-OV-3 by measuring: cell
      proliferation, modulation of matrix metalloproteinase (MMP)-2 and -9 expression,
      and cancer cell invasive potential. METHODS: Cell proliferation was evaluated by
      MTT assay, MMP activity by gelatinase zymography, and invasion through Matrigel.
      RESULTS: Human ovarian cancer cell growth was not significantly affected by the
      NM. Zymography demonstrated inhibition of MMP-2 secretion in a dose-dependent
      fashion with virtual total inhibition at 50 microg/mL NM concentration. Invasion
      of human ovarian cancer cells through Matrigel decreased in a dose-dependent
      fashion, with 90% inhibition at 500 microg/mL NM and 100% inhibition at 1000
      microg/mL NM (P < 0.0001). CONCLUSION: The combination of lysine, proline,
      arginine, ascorbic acid and green tea extract tested inhibited critical steps in
      cancer development and spread, such as MMP expression and invasion, indicating
      its potential as a treatment modality against ovarian cancer.

PMID- 16594918
TI  - Fetal aortic distension waveforms for evaluating cardiac function and changes in
      blood pressure: fetal lamb validation.
AB  - AIM: To investigate which part of the fetal aortic distension waveform is mainly
      influenced by changes in fetal cardiac contractility and aortic blood pressure.
      METHODS: In acute preparation, aortic distension waveforms were recorded using an
      echo-tracking system, and aortic and left ventricular pressure waveforms were
      obtained from six late-gestation catheterized fetal lambs. Dobutamine and
      angiotensin II were separately infused and the correlations between the maximum
      value in the first derivative of left ventricle pressure waveforms (Max dP/dt)
      and fetal blood pressure, and the parameters obtained from aortic distension
      waveforms were analyzed using linear regression analysis. RESULTS: With a change
      in cardiac contractility, the maximum value of first derivative of the systolic
      rising slope in the aortic distension waveform had a positive correlation with
      Max dP/dt (r = 0.93, P < 0.0001). With changes in fetal blood pressure, both the
      amplitude and the ratio of increase from the end diastolic diameter obtained from
      the aortic distension waveform had a significant positive correlation with aortic
      blood pressure amplitude (r = 0.60, P < 0.01; r = 0.61, P < 0.01, respectively).
      CONCLUSION: The maximum first derivative of the systolic rising slope in the
      aortic distension waveform and the amplitude in the aortic distension waveform
      enable us to non-invasively substitute for fetal cardiac contractility and aortic
      blood pressure amplitude, respectively.

PMID- 16594919
TI  - Immunological factors and their role in the genesis and development of
      endometriosis.
AB  - The article presents an overview of immunological factors and their role in the
      genesis and development of endometriosis, with emphasis on inflammatory cytokines
      and growth and adhesion factors. Although retrograde menstruation is a common
      phenomenon among women of reproductive age, not all women with retrograde
      menstruation suffer the disease. Development of endometriosis seems to be a
      complex process, facilitated by several factors, including quantity and quality
      of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in
      PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune
      surveillance and clearance of endometrial cells, and increased production of
      autoantibodies against endometrial cells. Potential biomarkers like cytokines and
      autoantibodies, upregulated during development of endometriosis, seem useful in
      the development of a non-surgical diagnostic tool. In this review work, the
      immune role in endometriosis is examined through the role of immunological
      factors in the genesis and development of the disease. Furthermore, it could be
      concluded that, although endometriosis can be treated using hormonal suppression,
      there is a need today for non-hormonal drugs, probably to modulate immune
      function, in order to confront the disease and alleviate pain or infertility
      without inhibition of ovulation.

PMID- 16594920
TI  - Sporadic fetal heart rate decelerations associated with electrocortical changes
      in fetal lambs.
AB  - AIM: The purpose of this study was to determine a relationship between sporadic
      fetal heart rate (FHR) decelerations and fetal electrocortical changes in
      physiologically normal sheep fetuses. MATERIALS AND METHODS: A total of 20
      experimental observations were conducted on eight chronically instrumented fetal
      lambs. For electrocorticogram (ECoG) recording, two stainless steel electrodes
      were implanted bilaterally on the fetal parietal skull. Classifications of ECoG
      tracings were visually divided into periods of low, high, intermediate and
      transitional voltage. During day and night observations, sporadic FHR
      decelerations related to fetal ECoG changes were counted. RESULTS: We found that
      65% of the total sporadic FHR decelerations occurred in relation to fetal ECoG
      changes. The largest number of sporadic FHR decelerations was associated with a
      switch from low voltage to high voltage ECoG (37%). However, the greatest
      frequency of sporadic FHR decelerations occurred during intermediate ECoG periods
      (34%). CONCLUSION: The majority of sporadic FHR decelerations observed in
      physiologically normal sheep fetuses were associated with fetal ECoG changes.

PMID- 16594921
TI  - Blastocyst development of 4-cell mouse embryos after laser destruction of one
      blastomere with or without its microsurgical removal.
AB  - AIM: To study the rate of blastocyst formation in 4-cell mouse embryos after
      laser destruction of one blastomere, with or without microsurgical removal of the
      destroyed blastomere. METHODS: Mouse embryos were randomly allocated to two
      control and two experimented groups. Control embryos were either non-manipulated
      (117 embryos) or underwent laser ablation of zona only (114 embryos).
      Experimented embryos had laser destruction of zona and the adjacent blastomeres.
      Destroyed blastomeres were either left in situ (115 embryos) or were
      microsurgically removed (107 embryos). They were cultured in sequential media for
      72 h and were assessed for cleavage/morula arrest and blastocyst formation rates.
      RESULTS: Embryos arrested at cleavage/morula stages were higher when destroyed
      blastomeres remained in situ (30.4%) than when they were immediately removed
      (15.0%, P < 0.05). Blastocysts in the group with immediate removal of the
      destroyed blastomeres (85%) were significantly higher than when destroyed
      blastomeres were left in situ (69.6%, P < 0.05). Blastocyst formation in the
      repaired embryos was significantly lower than the non-manipulated (91.5%) and the
      manipulated controls (94.8%, P < 0.05). Hatching blastocysts were highest in
      control embryos with zonal ablation (72.8%). Proportions of hatching/hatched
      blastocysts in embryos, with or without removal of destroyed blastomeres, were
      not significantly different (39.3% and 33.9%, respectively). The percentage of
      embryonic loss during an attempt at microsurgical repair was 6.1%. CONCLUSION:
      Microsurgical removal of destroyed blastomere was effective in restoring
      blastocyst development. It could reduce the rate of cleavage/morula arrest.

PMID- 16594922
TI  - Difference in the relative contribution of lean and fat mass components to bone
      mineral density with generation.
AB  - AIM: To investigate whether the relative contribution of body composition (lean
      and fat mass component) to bone mineral density (BMD) differs depending on
      generation or menopause. METHODS: Subjects were 302 premenopausal women aged 30
      49 years old and 197 postmenopausal women aged 50-69 years old. They were
      classified into four subgroups with 10-year increments. Age, height, weight and
      years since menopause (YSM) were recorded. Lumbar spine (L2-4), total body BMD,
      body fat mass, lean body mass (LBM), and the percentage of body fat (%fat) were
      measured using dual-energy X-ray absorptiometry. The correlation of body
      composition with BMD was investigated. RESULTS: The mean age at menopause was
      50.2 +/- 4.1 years old. On Pearson's correlation test, LBM was positively
      correlated with BMD of the two sites in all groups. In a group aged 60-69 years,
      both the %fat and body fat mass were correlated with BMD. On multiple regression
      analysis, LBM was the principal BMD determinant in women aged less than 60 years,
      while body fat mass and percentage fat were the principal BMD determinants in
      women aged 60-69 years. Mean %fat in the group aged 60-69 years was 35.5 +/-
      7.3%, which was significantly higher than that in the group aged 50-59 years
      (33.0 +/- 6.7%, P < 0.05). CONCLUSION: Although LBM still influences BMD up to 10
      years after menopause, the body fat mass initially influences BMD after 60 years
      of age. These difference may be attributable to certain aging-related factor(s).

PMID- 16594923
TI  - Spontaneous ectopic pregnancy occurring in the isthmic portion of the remnant
      tube after ipsilateral adnexectomy: report of two cases.
AB  - Two cases of spontaneous ectopic pregnancy occurring in the isthmic portion of
      the remnant tube after previous ipsilateral adnexectomy are presented.
      Laparoscopic observation and postoperative histopathological examination
      suggested intrauterine transmigration of the fertilized egg as the etiology.
      Laparoscopic excision of the remnant tube was performed and the postoperative
      course was uneventful in both cases. Attention should be paid to this unusual
      type of ectopic pregnancy while examining patients with previous history of
      adnexal surgery.

PMID- 16594924
TI  - Preoperative diagnosis of ovarian tumors, focusing on the solid area based on
      diagnostic imaging.
AB  - AIM: The objectives were to attempt to differentiate between benignancy and
      malignancy by focusing not on macroscopic finding of tumor sections, but on the
      solid areas by diagnostic imaging. To investigate the usefulness of diagnostic
      imaging for ovarian tumors, we examined the solid areas in the tumor and their
      shape and analyzed the relationship between these factors and the malignant
      potential. METHODS: Subjects were 921 surgical cases (1074 tumors) over a period
      of 7 years. Diagnostic images (ultrasonography, computed tomography and magnetic
      resonance imaging) were reread, focusing on the solid area. Tumors were
      classified into four groups according to the prominence of the solid area, and
      the findings were compared with the postoperative diagnosis. RESULTS: Of the
      cases, 718 indicated benign, borderline malignancy in 29 and malignancy in 174.
      The malignant potential of tumors with solid areas was significantly higher than
      those with no solid area. However, upon comparison among the different groups
      with solid areas, no significant differences were detected in terms of the
      frequency at which malignancies were detected, despite the differences between
      the groups with respect to size and shape. CONCLUSION: It is important for the
      treatment strategy that solid areas, even if small, should not be neglected, and
      that malignancies are found at high frequency regardless of shape, size and
      prominence.

PMID- 16594925
TI  - Analysis of ovarian tumors for the presence of human papillomavirus DNA.
AB  - AIM: The role of human papillomavirus (HPV) infection in ovarian tumorigenesis is
      uncertain. The objective of this study was to screen a collection of ovarian
      tumors for the presence of high-risk oncogenic HPV types 16, 18 and 33. METHODS:
      Twenty benign and malignant ovarian tumors were obtained from women undergoing
      pelvic surgery at a regional comprehensive cancer institution in North America.
      DNA was isolated from the snap-frozen tumors, and commercial polymerase chain
      reaction (PCR) detection sets were used to analyze the tumor DNA samples for the
      presence of DNA from HPV types 16, 18 and 33. RESULTS: The DNA from HPV types 16,
      18 and 33 was not detected in any of the ovarian tumors. CONCLUSIONS: Our
      findings do not support an association between infection with HPV types 16, 18
      and 33 and ovarian neoplasia in this patient population.

PMID- 16594926
TI  - Differences in urodynamic study, perineal sonography and treatment outcome
      according to urethrovesical junction hypermobility in stress urinary
      incontinence.
AB  - AIMS: To evaluate the differences in urodynamic study (UDS) and the perineal
      ultrasonography parameters between stress urinary incontinence (SUI) patients
      with or without urethrovesical junction (UVJ) hypermobility. Treatment outcomes
      following a retropubic urethropexy were also compared. METHODS: The records of
      164 SUI patients (<or=stage II), treated with retropubic urethropexy at our
      department between January 2001 and February 2004 were reviewed. The patients
      were categorized into a hypermobility group when the measured Q-tip angle was
      >or=30, and a non-hypermobility group when <30. All patients underwent UDS and
      perineal ultrasonography (US) preoperatively. A Burch urethropexy was performed
      regardless of the Q-tip result. All patients were reevaluated at 1 month and 3
      months, postoperatively, and every 3 months thereafter. RESULTS: Ninety-eight
      patients (60%) had an accompanying UVJ hypermobility and 66 (40%) did not. No
      significant differences regarding age, parity, body mass index (BMI), menopausal
      status, hormone replacement status, history of previous gynecologic surgery, or
      other medico-surgical illness were noted. UDS parameters demonstrated a
      significant difference between the groups, but were in the normal range. The
      significant difference noted in the perineal US was the bladder neck descent
      (BND). Following retropubic urethropexy, the success rates after 1 year were 94%
      and 91% for the hypermobility group and the non-hypermobility group,
      respectively, showing no statistical significance. CONCLUSION: The success rates
      of Burch urethropexy in the two groups were similar. This result suggests that
      either the Q-tip is an inaccurate method of evaluating UVJ hypermobility or the
      presence of UVJ hypermobility does not negatively affect the treatment outcome of
      a Burch urethropexy.

PMID- 16594927
TI  - Giant paraovarian myxoma.
AB  - We present an extremely rare case of a successfully operated giant (6700 g)
      paraovarian myxoma and uterus myomatosus in a 49-year-old woman. Preoperative
      examination (biochemical investigations, ultrasound and computed tomography scan)
      and perioperative findings did not identify a malignant tumor so that total
      abdominal hysterectomy/bilateral salpingo-oophorectomy and tumorectomy was chosen
      to treat the patient. Histologically, the tumor was clearly differentiated from
      the surrounding tissue. In solid regions there were spindle-shaped cells arranged
      in sheaves and within the profuse, well-vascularized myxomatous stroma there were
      star-shaped cells. Immunohistochemical analysis showed that tumor cells were
      positive to vimentin and smooth muscle actin. Electron microscopic analysis
      showed that tumor cells had ultrastructural characteristics that corresponded to
      cells in fibroma and thecoma in a profuse intercellular matrix, which confirmed
      the result of light microscopy.

PMID- 16594928
TI  - Ranking the contributing risk factors in venous thrombosis in terms of
      therapeutic potential: Virchow's triad revisited.
AB  - AIM: Thromboemoblism is an attendant feature of a variety of pathological
      conditions. We reconsidered Virchow's pathogenetic triad of stasis, humoral
      factors and vascular wall pathologies in the light of platelet behavior in vivo.
      METHODS: Rat mesenteric microcirculation was examined by intravital microscopy.
      After isolated rat platelets had been injected i.v. into rats, their behavior in
      venules was examined under the following conditions: stasis from pressure,
      hemoconcentration from erythropoietin injections, or endothelial damage from
      tumor necrosis factor-alpha. RESULTS: In the endothelial damage group, platelets
      displayed transient adhesion and rolling, while some platelets exhibited
      stationary adhesion to venular endothelium. The stasis and hemoconcentration
      groups exhibited only a slight change in adhesive response. CONCLUSION:
      Endothelial dysfunction appears to be the most important contributing factor in
      the development of venous thrombosis. As such, targeting this dysfunction is
      suggested for therapeutic intervention.

PMID- 16594929
TI  - Effectiveness of microlaparoscopy in the diagnosis of premature ovarian failure.
AB  - AIM: Premature ovarian failure (POF) cases contain a mixture of cases possessing
      follicles (type A) and those depleted of follicles (type B). Differentiation
      between the two types is important because the treatment policy and pregnancy
      prognosis vary greatly. The objective of this study was to examine the usefulness
      of microlaparoscopy in the differentiation of types A and B. METHODS: Among 66
      patient with POF diagnosed at our department between May 1996 and April 2004, 47
      patients who gave informed consent and underwent microlaparoscopy were studied.
      The cases were divided into four groups based on the laparoscopic ovarian
      morphology. These groups were analyzed with respect to patient background, blood
      hormone levels, antinuclear antibody positive rate, visualization of the ovary on
      transvaginal ultrasonography, presence or absence of follicles in biopsy
      specimen, and number of follicles. RESULT: No significant differences in patient
      background and serum hormone levels were observed between groups. There was a
      tendency of increase in antinuclear antibody positive rate, increase in
      proportion of cases with follicles, and increase in number of follicles as the
      ovarian morphology approached normal. Transvaginal ultrasonography failed to
      identify the ovary in all the patients. CONCLUSION: Microlaparoscopy is useful in
      the differentiation between type A and B POF, and is further expected to become
      an indicator of response to treatment.

PMID- 16594930
TI  - Vitamin K2 treatment for postmenopausal osteoporosis in Indonesia.
AB  - AIM: To investigate the effect of vitamin K2 (menatetrenone) treatment on bone
      mineral density (BMD) and a bone metabolic marker (osteocalcin) in postmenopausal
      women with osteoporosis living in Indonesia. METHODS: A double-blind randomized
      placebo-controlled study of 63 postmenopausal women with osteoporosis. The
      vitamin K2 group (n = 33) received 45 mg menatetrenone and 1500 mg calcium
      carbonate per day and the control group (n = 30) received placebo and 1500 mg
      calcium carbonate per day for 48 weeks. BMD of lumbal spine (L2-L4), osteocalcin
      (OC) and undercarboxylated OC were measured before, 24 and 48 weeks after
      initiation of the treatment. RESULTS: After 48 weeks of treatment, the mean
      percentage change of lumbar BMD in the vitamin K2 group was significantly higher
      (P < 0.05) than that of the control group. The undercarboxylated OC level
      decreased by 55.9% in the menatetrenone group and 9.3% in the control group
      compared with the baseline level. The difference between the two groups was
      significant (P < 0.01). The adverse events were three minor gastrointestinal
      cases, which subsided after temporary cessation of therapy. CONCLUSIONS:
      Treatment with 45 mg vitamin K2 with 1500 mg calcium per day for postmenopausal
      women with osteoporosis for 48 weeks resulted in a significant increase in lumbar
      BMD and a significant decrease in undercarboxylated OC levels.

PMID- 16594931
TI  - Small bowel perforation without tumor recurrence after radiotherapy for cervical
      carcinoma: report of seven cases.
AB  - AIM: We describe the clinical presentation, evaluation, management and outcome of
      patients experiencing small bowel perforation following radiation therapy for
      cervical cancer. METHODS AND MATERIALS: A database consisting of 95 Japanese
      women with stage 0-4 A cervix cancer treated between 1991 and 2004 contained
      seven patients (7.4%) with small bowel perforation. RESULTS: The median age at
      the time of perforation was 72.5 years (range 62-78). The median time from
      completion of radiotherapy to perforation was 6 months (range 2-58). Surgery (one
      small bowel resection and anastomosis with diversion; six small bowel resection
      and anastomosis) was performed immediately in all seven patients. One of seven
      patients died of small bowel perforation (i.e. mortality rate was 14%). Bowel
      adhesion was detected during the operation in only three cases (43%). Signs of
      peritonitis were absent in six cases (86%). Severe abdominal pain was seen in all
      seven patients. The perforation site was ileum in all seven cases. In all
      patients, pathological changes were compatible with postirradiation injury of the
      gastrointestinal tract. CONCLUSIONS: The presenting complaints of patients with
      bowel perforation following radiotherapy vary, and signs of peritonitis may be
      absent. Emergency physicians must be alert for these complications in patients
      who have been treated with radiotherapy.

PMID- 16594932
TI  - Metronidazole with Lactacyd vaginal gel in bacterial vaginosis.
AB  - AIM: To assess the efficacy and tolerability of lactic acid (Lactacyd vaginal
      gel; LVG) when given as an adjunct to metronidazole in the treatment of bacterial
      vaginosis (BV) among Filipino patients. METHODS: A multicenter, open-labeled,
      controlled, randomized, three-arm comparative study on 90 women aged 18 years or
      over with clinically and microbiologically proven BV. RESULTS: The lactobacilli
      colony count significantly increased over time in all three arms. At day 14,
      growth of lactobacilli was significantly higher among patients in the lactic acid
      gel and combination treatment arms. Significant reduction of malodorous vaginal
      discharge (whiff test) and lowest recurrence of BV were noted in the
      metronidazole plus lactic acid gel arm. Regarding disappearance of signs of BV,
      there was significant decrease in the pH level and frequency of clue cell
      positive patients across time but was not significantly different across
      treatment groups. Only one patient (3%, 1/60) among those who received lactic
      acid gel complained of increased curd-like discharge. Six patients (10%, 6/60)
      who received metronidazole complained of epigastric pain/discomfort, dizziness
      and dyspnea. CONCLUSIONS: Lactic acid gel (LVG) is safe and as efficacious as
      metronidazole in the treatment of BV. There is evidence that LVG when combined
      with metronidazole is superior to metronidazole alone in promoting lactobacilli
      colonization. LVG as an adjunct to metronidazole, having the least number of
      recurrent BV, appears to result in better long-term treatment effect on bacterial
      vaginosis.

PMID- 16594933
TI  - Pregnancy complicated by multiple pituitary hormone deficiencies.
AB  - We report a case of pituitary dwarfism and diabetes insipidus due to pituitary
      stalk transection in a pregnant Japanese woman, 138 cm in height, born by breech
      delivery with no evidence of ante- or intrapartum asphyxia. The patient had no
      central nervous disturbance, was diagnosed with pituitary dwarfism during
      childhood and was treated at another hospital with growth hormone supplement from
      5 to 14 years of age. This patient was referred to our department at 17 weeks'
      gestation due to a change of residence. At 30 weeks' gestation, she was
      hospitalized for assessment of hydronephrosis and polyuria (15-20 L/day).
      Analysis of a 24-h urine sample showed creatinine clearance of 157 mL/min and
      urine osmolality of 38 mOsm/L. The patient's urine output decreased after
      receiving a test dose of 0.75 g of 1-desamino-8-D-arginine vasopressin (DDAVP).
      Cranial magnetic resonance imaging showed transection of the pituitary stalk.
      Subsequently, the patient's urine output was well controlled by a maintenance
      dose of 0.275 mL/day intranasal DDAVP. A cesarean section was performed at 37
      weeks, as the patient height was 138 cm, and a pelvic X-ray showed cephalopelvic
      disproportion. She delivered a female baby weighing 2302 g, and both 1- and 5-min
      Apgar scores were 9. The patient was followed up after 4 months and showed no
      visual deterioration or polyuria while on DDAVP therapy, while the neonate grew
      favorably.

PMID- 16594934
TI  - Role of family in alcohol and substance abuse.
AB  - Abuse is a family disease, which requires joint treatment of family members.
      Family is an important part of the diagnosis and treatment chain of alcohol and
      substance abuse. Abuse of alcohol and substance is a response to fluctuations in
      the family system. In consideration of interactions within the system, it seems
      an important requirement that the clinician involves, and maintains the presence
      of, the family in its entirety in the treatment process. A family often needs as
      much treatment as the family member who is the abuser of alcohol or a substance.
      In this regard, participation of the family in the treatment process as group
      members and by assuming a supportive role are assets in terms of preventing
      relapse, and extending clean time, and also very important for solving conflicts
      that give rise to abuse of alcohol or substances. Accordingly, it is important to
      know the family structure and its role in the treatment process. This article
      covers a review of family systems separately in terms of alcoholism and substance
      abuse.

PMID- 16594935
TI  - Transcranial magnetic stimulation: potential treatment for tinnitus?
AB  - Tinnitus is a common and often severely disabling disorder for which there is no
      satisfactory treatment. Transcranial magnetic stimulation (TMS) is a new, non
      invasive method of modifying the excitability of the cerebral cortex, which has
      proven effective in auditory hallucinations and other disorders. Some early
      studies have been published in which TMS has been trialed in the treatment of
      tinnitus. The aim of the present paper was to examine the literature and consider
      the potential for TMS as a therapy in tinnitus. A thorough search of the tinnitus
      and TMS literature was conducted, and all available relevant material was
      examined. Discussions were held with leaders in both fields. Tinnitus is common
      and there are no effective treatments. It is frequently associated with deafness,
      and may be the result of a pathological plastic process, secondary to loss of
      innervation of the outer hair cells of the cochlea. Neuroimaging studies
      demonstrate increase blood flow to the primary and secondary auditory cortices,
      particularly on the left side. Transcranial magnetic stimulation is a non
      invasive method of perturbing and inducing change in the cerebral cortex. It uses
      electromagnetic principles and has been successfully employed in the treatment of
      other conditions associated with increased activity of the cerebral cortex. A
      small number of studies have suggested that TMS may be effective in the treatment
      of tinnitus. There is a good theoretical basis and early research evidence
      suggesting that TMS may have treatment potential in tinnitus. Further, larger
      studies are necessary.

PMID- 16594936
TI  - Non-verbal learning is impaired in very mild Alzheimer's disease (CDR 0.5):
      normative data from the learning version of the Rey-Osterrieth Complex Figure
      Test.
AB  - Mild cognitive impairment (MCI) is a transitional state between normal aging and
      dementia. Although there have been some studies on the role of verbal memory in
      learning ability, there have been no reports on the part played by visual memory.
      In the present study, the Rey-Osterrieth Complex Figure Test (RCFT) was given to
      healthy subjects and to those with MCI to determine if visual memory was
      maintained in these two groups. Additionally, normative data from the learning
      version of the RCFT for Japanese subjects were examined, for purpose of
      reference. The participants consisted of 381 clinical dementia rating (CDR) 0
      subjects and 137 CDR 0.5 subjects who could perform the full set of RCFT tasks.
      The CDR 0 group had significantly higher scores than the CDR 0.5 group in all
      trials. The CDR 0 participants also showed a significant step-by-step learning
      effect, while the CDR 0.5 participants did not show a significant learning
      effect. These results suggest that the CDR 0 participants maintained intact
      learning abilities of encoding and retrieval, while the CDR 0.5 participants did
      not do so; but further studies will be needed to clarify these findings.

PMID- 16594937
TI  - Quality of life, depression, and stress in breast cancer women outpatients
      receiving active therapy in Taiwan.
AB  - The aims of the present study were to compare the quality of life (QoL),
      depression and stress between patients with malignant breast cancer and those
      with benign breast tumors. The present study also examined the factors related to
      QoL among the patients who were receiving active treatment for breast cancer.
      Among the 97 patients participating in the study, 73 patients were diagnosed as
      having malignant breast cancer (malignant group) and 24 as having benign tumors
      (benign group). All the participants completed the World Health Organization
      Questionnaire on Quality of Life to determine their QoL. The level of depression,
      stress, and demographic characteristics were also collected. Quality of life,
      depression and stress were compared between the malignant and benign groups, and
      the factors related to QoL were also examined. It was found that the malignant
      group had poorer physical and psychological QoL and higher life stress.
      Depression was significantly associated with QoL for both the malignant and
      benign groups, and the stress from health problem was the most significant
      predictors for QoL among the malignant group. The breast cancer patients suffered
      more severe psychological difficulty under active treatment than did the benign
      group patients. This will have great impact on their QoL, as in Western society.
      Depression and stress need to be recognized and aggressive psychological and/or
      medical intervention needs to be carried out in order to diminish the impact on
      QoL.

PMID- 16594938
TI  - Oral cenesthopathy examined by Rorschach test.
AB  - Experience of abnormal pains and unusual sensations in the mouth without a
      somatic base, for example abnormal mucus secretion, pulling sensation on the jaw
      or teeth, or a vibrating sensation, is termed 'oral cenesthopathy'. Psychological
      factors were investigated in terms of cognitive functions and personality
      tendencies, using Rorschach test in 28 patients with this condition (three men
      and 25 women). In oral cenesthopathy patients (i) the processing of new
      information is inefficient; (ii) the necessary resources for social adaptation
      are lacking, emotional control is inadequate, and uncomfortable emotions are
      expressed less; and (iii) with regard to interpersonal interaction, less interest
      is shown in others, trust in others is diminished, and they tend to have a higher
      Coping Deficit Index.

PMID- 16594939
TI  - Correlates of methamphetamine use for Taiwanese adolescents.
AB  - The aim of the present study was to assess the associations between
      methamphetamine (MAP) use and psychiatric comorbidity, individual attitudes and
      personal knowledge of MAP use, family characteristics and peer factors in
      Taiwanese adolescents via a case-control study. Two hundred adolescent MAP users
      and 400 adolescent non-users were recruited. Their psychiatric comorbidity,
      attitudes and knowledge toward MAP use, family characteristics and peer
      interactions were assessed systematically. The associations between MAP use and
      those factors were examined by univariate and multivariate analysis. In
      conditional logistic regression analysis, comorbid conduct disorder, attitude
      favorable to MAP use and poor knowledge of MAP use, disrupted parenting, lower
      caregiver education level, having friends using or providing MAP and actively
      interacting with peers were associated significantly with MAP use. Adolescent MAP
      use was correlated with multiple factors that lie within individuals and the
      interaction with their family and peers. Correlates of MAP use identified in the
      present study may be helpful for the design and implementation of preventive
      intervention.

PMID- 16594940
TI  - Distress and functioning in mixed anxiety and depressive disorder.
AB  - The aim of the present study was to evaluate the validity of mixed anxiety and
      depressive disorder (MADD) with reference to functional characteristics and
      symptomatic characteristics in comparison with anxiety disorders, depressive
      disorders, and groups showing subthreshold symptoms (exclusively depressive or
      anxiety related). The present study was carried out in the following three
      medical settings: two psychiatric and one primary care. Patients seeking care in
      psychiatric institutions due to anxiety and depressive symptoms and attending
      primary medical settings for any reason were taken into account. A total of 104
      patients (65 women and 39 men, mean age 41.1 years) were given a General Health
      Questionnaire (GHQ-30), Global Assessment of Functioning (GAF) and Present State
      Examination questionnaire, a part of Schedules for Clinical Assessment in
      Neuropsychiatry, Version 2.0. There were no statistically relevant differences
      between MADD and anxiety disorders in median GHQ score (19 vs 16) and median GAF
      score (median 68.5 vs 65). When considering depressive disorders the median GHQ
      score (28) was higher, and median GAF score (59) was lower than that in MADD. In
      groups with separated subthreshold anxiety or depressive symptoms, median GHQ
      scores (12) were lower and median GAF scores (75) were higher than that in MADD.
      The most frequent symptoms of MADD are symptoms of generalized anxiety disorder
      (GAD) and depression. Mixed anxiety and depressive disorder differs significantly
      from GAD only in higher rates of depressed mood and lower rates of somatic
      anxiety symptoms. Distinction from depression was clearer; six of 10 depressive
      symptoms are more minor in severity in MADD than in the case of depression.
      Distress and interference with personal functions in MADD are similar to that of
      other anxiety disorders. A pattern of MADD symptoms locates this disorder between
      depression and GAD.

PMID- 16594941
TI  - Cognitive impairment in people diagnosed with end-stage liver disease evaluated
      for liver transplantation.
AB  - Cognitive impairments are common in patients with end-stage liver disease (ESLD).
      The aim of the present study was to identify and characterize the
      neuropsychological deficits between groups of patients with a variety of causes
      of ESLD and to assess the impact of heavy alcohol use on cognitive functioning.
      Cognitive functioning in 300 consecutive outpatients presenting for liver
      transplantation evaluation was assessed using the Repeatable Battery for the
      Assessment of Neuropsychological Status (RBANS). All patients underwent a
      psychiatric interview and a physical and laboratory assessment. The prevalence of
      neuropsychological impairment was highest among patients with liver disease
      secondary to alcohol. Poor performance on neuropsychological testing was
      correlated strongly with the severity of liver disease as measured by the model
      for end-stage liver disease (MELD). After controlling for the linear effects of
      MELD in subsequent analysis, a group difference emerged in patients with
      cholestatic liver disease showing less cognitive impairment when compared to all
      other groups. After controlling for the severity of liver disease, those patients
      with a history of alcohol abuse or dependence were found to perform more poorly
      on neuropsychological testing than those patients without such a history.
      Furthermore, the presence of these cognitive impairments predicted disability
      independent of the severity of the underlying liver disease.

PMID- 16594942
TI  - Impact of infant health problems on postnatal depression: pilot study to evaluate
      a health visiting system.
AB  - This pilot study aimed to elucidate whether or not mothers who receive neonatal
      home visits tend to suffer from depressive disorders during the first postpartum
      year and to examine what kinds of factors were related to the postnatal
      depression observed in these mothers. The subjects consisted of 70 Japanese
      mothers who received neonatal home visits and completed the 1-year study. At
      their first visit, the health visitors asked about their personal backgrounds and
      early postpartum mood, and depression was assessed by a Japanese translation of
      the Edinburgh Postnatal Depression Scale (EPDS). At 12 months postpartum, a
      diagnostic interview using the Structured Clinical Interview for DSM-IV (SCID)
      was performed to confirm the maternal diagnosis by a psychiatrist. An assessment
      of infant development using the Denver Developmental Screening Test (DDST) was
      administered to each infant by a psychologist. Nineteen mothers (27%) were
      categorized as having had a new onset of depression (12 major depressive
      disorders and seven depressive disorders not otherwise specified). In comparison
      to the non-depressed mothers, infant-related health problems that required either
      outpatient treatment or hospitalization were significantly related to postnatal
      depression. Pediatric diseases in infants did not always precede their mother's
      depression. The extra burden of caring for a sick infant tends to increase the
      risk of developing postpartum depression. As a result, neonatal home visits by
      health visitors may therefore be a potentially crucial opportunity to provide
      emotional support, particularly for mothers with the extra burden of having to
      care for sick infants.

PMID- 16594943
TI  - Efficacy and safety of donepezil in patients with dementia with Lewy bodies:
      preliminary findings from an open-label study.
AB  - The objectives of the present study were first to determine the feasibility of
      conducting a randomized clinical trial of 5 mg/day donepezil in patients with
      mild to moderate dementia with Lewy bodies (DLB) and second, to obtain
      preliminary data of possible intervention effects. Twelve patients with probable
      DLB were evaluated at weeks 4, 8, and 12 using modified Neuropsychiatric
      Inventory (NPI) with an extra domain to additionally evaluate fluctuation in
      cognitive functions (NPI-11); the Japanese version of Alzheimer's Disease
      Assessment Scale-cognitive subscale (ADAS-J cog); and the Unified Parkinson's
      Disease Rating Scale (UPDRS). The NPI-11 scores were significantly improved at
      weeks 8 and 12 compared with baseline. Despite a significant improvement in ADAS
      J-cog at week 4, no more improvement was noted thereafter. Deterioration was not
      noted in UPDRS scores. Donepezil is expected to be therapeutically useful and
      safe in treating DLB patients, indicating marked improvements in behavioral and
      psychological symptoms of dementia (BPSD) rather than in cognitive deficit,
      without deteriorating parkinsonism.

PMID- 16594944
TI  - Nurses' collaboration with physicians in managing medication improves patient
      outcome in acute psychiatric care.
AB  - The aim of the present paper was to examine the impact of nurses' collaboration
      with physicians in medication management on patient outcome in acute psychiatric
      care. Data for 143 patients with schizophrenia were assessed based on information
      given by nurses and physicians in charge. Twenty-two patients were defined as a
      collaborative group when physicians changed medication after receiving reports
      that nurses perceived the necessity to change. A control group was formed from
      the 50 patients when nurses perceived the necessity to change medication but did
      not tell physicians, or nurses advised of the necessity to physicians but
      medication was not changed. Physicians retrospectively evaluated patients' social
      functioning and acceptance of medication at admission and discharge. Social
      functioning was measured by Global Assessment of Functioning (GAF), and
      acceptance of medication by a single item using Japanese version of Schedule for
      Assessment of Insight (SAI-J). Changes in the scores from admission to discharge
      on GAF and acceptance of medication were defined as outcome measures. Nurses
      recognized the necessity to change medication for patients with frequent
      aggressive behavior and younger age. Compared with the control group, the
      collaborative group had less instruction for use of drugs, and more perceived
      necessity to decrease the current dose or the number of drugs because of stable
      symptoms. The collaborative group demonstrated significantly greater improvement
      in social functioning. The collaborative group improved acceptance of medication,
      although there were no significant differences between the two groups. Nurses'
      collaboration with physicians in medication management improved patient outcome
      in acute psychiatric care.

PMID- 16594945
TI  - Pathway to psychiatric care in Bali.
AB  - The aim of the present study was to trace the help-seeking pathway of mental
      patients and to elucidate the role of traditional healing in Bali. The source of
      care before attending Bangli Mental Hospital (Bali) of 54 consecutive patients
      with no prior psychiatric treatment was investigated. Subjects who had sought
      help from traditional healers were asked to evaluate treatment effect
      retrospectively according to a 5-point scale. The pathway to psychiatric care was
      dominated by traditional healers. Of the patients, 47 (87.0%) consulted a healer
      (mean number 2.9) before visiting the mental hospital. Consultation with the
      healers was associated with treatment delay. However, of the 137 traditional
      healers on the pathway, 11 (8.0%) recommended that the subjects to go to a mental
      hospital, and all 11 subjects immediately followed the advice. Of the 47
      subjects, 14 (29.8%) evaluated the treatment effect as much improved by at least
      one traditional healer on the pathway, although they ultimately attended the
      mental hospital. Subjects without psychotic symptoms tended to evaluate the
      treatment effect as much improved more often than psychotic subjects. Traditional
      healers function not only as a barrier to reaching psychiatric care, but as
      either an effective provider of care or a decision-making support for seeking
      help from psychiatric care for some mental patients in Bali. The knowledge and
      recognition of psychological disorders by the traditional healers are crucial for
      early treatment intervention for psychiatric patients.

PMID- 16594946
TI  - Reliability and validity of communication skills questionnaire (CSQ).
AB  - A new and easy evaluation method of communication skills has been developed using
      the Communication Skills Questionnaire (CSQ), which can be self-administered or
      administered by family members and medical staff. The reliability and validity of
      this CSQ were evaluated. Eighty-seven patients with mental disorders and 100
      normal controls participated in a self-rating evaluation of the CSQ, and 55
      family members and four medical personnel also participated in objective rating.
      The CSQ contained 29 items and these items were divided into three categories:
      cooperative skills (17 items), assertive skills (six items) and general
      communication skills (six items, mainly non-verbal skills). Internal
      consistencies of all groups were between 0.91 and 0.97. Test-retest reliability
      values for patients, family members and medical staff were between 0.90 and 0.95.
      Interrater reliability of medical staff was 0.73. The total scores had a moderate
      positive correlation with Global Assessment of Functioning (GAF) score and
      doctor's impression of communication skill evaluated on a 10-point scale. The
      patient group had a lower CSQ score than that of controls and the score
      differences between controls and patients with schizophrenia, mood disorders or
      eating disorders were statistically significant. This questionnaire is a good
      psychometric method of evaluating the communication skills of patients.

PMID- 16594947
TI  - Somatic symptoms for predicting depression: one-year follow-up study in annual
      health examinations.
AB  - It has recently been noted that screening for depression can improve clinical
      outcomes. The purpose of the present study was to examine whether somatic
      symptoms reported at health examinations predicted depression in the following
      year. Subjects were 1066 Japanese workers (732 men, mean age 35 years) attending
      annual health examinations at an institute in two successive years. A self
      administered questionnaire including items of 12 major somatic symptoms was given
      to all the subjects. Then clinical interviews of the DSM-IV were used to diagnose
      major depression and minor depression in both years. In addition, the 17-item
      Hamilton Depression Scale (HDS-17) was measured as one of the outcomes of
      depression in the following year. The prevalence of major (minor) depression was
      3.7 (7.8)% at baseline and 3.4 (5.9)% for the following year, respectively. The
      following year's HDS-17 scores were higher (all P < 0.05) in those who had
      complained of each somatic symptom at baseline than in those who had not. Three
      somatic symptoms (low back pain, dizziness, and abdominal pain) at baseline were
      significant risk factors of major depression for the following year. Dizziness at
      baseline significantly predicted major and minor depression for the following
      year as well. Somatic symptoms may be good predictors to screen for depression at
      health examination.

PMID- 16594948
TI  - Association between dopamine receptor D1 A-48G polymorphism and methamphetamine
      abuse.
AB  - Several lines of evidence have suggested that substance abuse is mediated by the
      dopaminergic rewarding system, primarily through the activity of the dopamine
      receptor D1 (DRD1). The purpose of the present study was to evaluate the
      association of DRD1 A-48G polymorphism with methamphetamine (MAP) abusers and MAP
      induced psychosis patients. A total of 363 MAP abusers and 425 healthy normal
      controls were enrolled. The structural Diagnostic Interview for Genetic Study was
      used to evaluate all MAP abusers. The MAP abusers were classified into psychosis
      (n = 135) and non-psychosis (n = 228) groups. A-48G polymorphism was determined
      by polymerase chain reaction-restriction fragment length polymorphism. The
      results show that male sex and a higher frequency of MAP abuse were the
      predisposing factors in the development of MAP psychosis. The DRD1 -48G allele
      frequency in the MAP psychosis group, non-psychosis group and the healthy normal
      controls was 0.14, 0.18 and 0.16, respectively. No association was found between
      DRD1 A-48G polymorphism and MAP abuse and MAP psychosis. However, the data
      provided additional evidence of ethnicity-related differences in the distribution
      of polymorphism in comparison to previous studies.

PMID- 16594949
TI  - Increased inhibition and decreased facilitation effect during a lexical decision
      task in children.
AB  - Widespread theories propose that implicit memory is established in the early
      stages of development, while explicit memory continues to develop until later
      stages. However, recent studies have argued that implicit memory changes
      developmentally. In order to elucidate the differences of implicit memory and
      semantic memory structures between children and adults, a single-word
      presentation method was developed using lexical decision tasks in which repeated
      real words, related real words, unrelated real words and pseudowords were
      presented in a list. Semantic priming and repetition priming using a single-word
      presentation method were employed in 25 children and 18 adults. Reaction time
      (RT) and correct rate for real words following pseudowords served as the base.
      Inhibition effect was defined as an increase in RT between a real word preceded
      by an unrelated real word and a real word preceded by a pseudoword. Facilitation
      effect was defined as a decrease in RT between a real word preceded by a related
      real word and a real word preceded by a pseudoword. Although the effect sizes of
      semantic priming did not differ between children and adults, the inhibition
      effect was larger and the facilitation effect was smaller in children. Repetition
      priming in children did not differ from that in adults. These findings challenge
      the idea of developmental invariance in implicit memory, suggesting that the
      strength of links between nodes in the semantic network increases and the range
      of spreading activation expands developmentally.

PMID- 16594950
TI  - Twelve-month use of mental health services in four areas in Japan: findings from
      the World Mental Health Japan Survey 2002-2003.
AB  - The aim of the present study was to provide basic descriptive data regarding
      utilization of 12-month mental health services in the Japanese community
      population. Face-to-face household surveys were carried out in four areas (two
      urban cities and two rural municipalities), and a total of 1663 persons
      participated (overall response rate: 56.4%). For data collection, the structured
      psychiatric interview, World Mental Health version of the World Health
      Organization Composite International Diagnostic Interview (WMH-CIDI) was used,
      allowing DSM-IV diagnoses, severity, and service utilization. It was found that
      7.3% of total respondents had received any service, either professional or non
      professional, in the past 12 months, including 20.0% of those with 12-month DSM
      IV disorders and 6.2% of those without. Thirty-three percent of those with any
      mood disorder used any service, and 26.8% of those used some type of health care.
      The probability of people with 13-15 years of education receiving mental health
      treatment was fourfold higher than those with >or=16 years of education. Gender,
      age, or income were not found to contribute to utilization of mental health
      services. The results confirm that the majority of people with a recent
      psychiatric disorder have not used mental health care or other support systems.
      The mental health care system in Japan has improved over the past decade, but not
      enough for people suffering from mental disturbances.

PMID- 16594951
TI  - Seasonality of birth in patients with schizophrenia in Japan.
AB  - Although most Western studies have found a birth excess during winter or early
      spring among patients with schizophrenia, this has not been found in Japanese
      samples. The purpose of the present paper was to investigate this finding using a
      large Japanese sample. Distributions of monthly birth numbers of patients with
      schizophrenia were compared to those of the general population. Patients were
      from the governmental data, numbering 88 788. A significant birth excess during
      winter to early spring was found in male and female subjects with schizophrenia
      compared to the general population. There is a significant birth excess during
      winter to early spring for schizophrenia in Japan. The authors consider that the
      discrepancy between the current study and the previous Japanese studies was
      caused by small sample size and selection bias in the previous Japanese studies.

PMID- 16594952
TI  - Clinical neurological abnormalities in young adults with Asperger syndrome.
AB  - Children with Asperger syndrome (AS), a neurodevelopmental disorder falling in
      the autism spectrum disorders, have an increased rate of neurological
      abnormalities, especially in motor coordination. While AS is a lifelong
      condition, little is known about the persistence of neurological abnormalities in
      adulthood. Twenty young adults with AS were compared with 10 healthy controls
      using a structured clinical neurological rating scale. The score for neurological
      abnormalities was higher in the AS group. In addition, a subscore for
      neurological soft signs indicating defective functioning of the central nervous
      system with a non-localizing value was significantly higher in the AS subjects.
      This preliminary study indicates that neurological abnormalities, soft signs in
      particular, represent a non-specific vulnerability factor for AS. Consistent with
      other features of AS, neurological abnormalities seem to persist into adulthood.

PMID- 16594953
TI  - Clozapine in schizophrenia patients with recurrent catatonia: report of two
      cases.
AB  - Prolonged catatonia can be a source of extremely serious morbidity and mortality.
      Lorazepam is effective in rapidly relieving most cases of catatonia. Reports have
      also shown that second-generation antipsychotic drugs are also efficacious in
      relieving catatonia. This report describes two schizophrenia patients who
      demonstrated recurrent catatonic features mutism and stupor. Both patients were
      treated with lorazepam, diazepam or electroconvulsive therapy (ECT). Patient 1
      responded well and rapidly to lorazepam each time catatonia happened; but
      catatonia recurred once a year under treatment with many antipsychotic drugs.
      Patient 2 had catatonia features associated with discontinuing or decreasing
      clozapine. With each recurrent episode, the duration of catatonia increased,
      requiring an increased dosage of benzodiazepine. The patient's response to
      lorazepam and ECT gradually decreased, until the patient had almost no response
      to lorazepam, diazepam or ECT. Both patients had no recurrence during a period of
      2-year follow up with continuous clozapine therapy.

PMID- 16594954
TI  - Childhood abuse and adult violence in homeless people.

PMID- 16594956
TI  - New patients, new lessons, new thinking in inflammatory bowel disease: World
      Congress of Gastroenterology Symposium, Montreal, Canada, September 2005.

PMID- 16594955
TI  - Paroxetine-induced excessive yawning.

PMID- 16594958
TI  - Inflammatory bowel disease: the view of the surgeon.
AB  - Despite advances in medical therapy, surgery is required in approximately 30-40%
      of patients with ulcerative colitis (UC) and 70-80% of patients with Crohn's
      disease (CD) at some point during their lifetime. For patients with UC, surgery
      may be curative, whereas recurrence of CD following surgery is common due to the
      potentially pan-enteric distribution of the disease. As a result, the indications
      and surgical management of the disease may be quite different. For UC, the
      surgeon is involved in the identification of new cases, management of severe
      disease, recognition of dysplasia and restorative proctocolectomy. Most of the
      advances in surgery for UC have been in novel techniques relating to the ileal
      pouch-anal anastomosis, which can now be performed safely for UC with a 10% pouch
      failure rate long term. For CD, the surgeon is involved in the management of
      small bowel and ileo-colonic disease, Crohn's colitis and perianal disease.
      Advances in the surgical management of CD include strictureplasty for extensive
      small bowel disease, laparoscopic ileo-caecal resection and a combined medical
      and surgical approach to perianal disease. For both CD and UC close liaison
      between the gastroenterologist and colorectal surgeon is essential.

PMID- 16594957
TI  - What's new: innovative concepts in inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) has been the subject of recent intense research
      and development. A greater insight into the basic pathological mechanisms of
      ulcerative colitis (UC) and Crohn's disease (CD) has resulted in the emergence of
      more sophisticated and effective management options. Additionally, established
      therapies are attracting renewed interest with novel dosage regimens and new
      formulations offering improved efficacy whilst maintaining an excellent tolerance
      profile. High dose 5-aminosalicylic acid (5-ASA) has been a focus for
      investigation in recent clinical trials. The ASCEND study, which compared a 4.8
      g/day dose with a 2.4 g/day dose, demonstrated that high dose mesalazine was
      significantly superior in achieving treatment success and symptom control, whilst
      maintaining a comparable tolerance and safety profile. The development of
      biotechnology agents targeted against tumour necrosis factor (TNF) provides
      promise of new treatment options in both CD and UC. The efficacy of CDP571,
      adalimumab and certolizumab have been investigated in CD, and infliximab, which
      is currently approved as an agent in inflammatory and fistulizing CD, has also
      been recently investigated in UC. Investigational pipeline molecules such as
      natalizumab, MLN-02, an anti-interleukin 12 antibody and sargramostim, have also
      shown encouraging results from early studies and are now undergoing evaluation in
      large clinical trials.

PMID- 16594959
TI  - New patients: should children be treated differently?
AB  - Inflammatory bowel disease (IBD) in childhood is often diagnosed at a vulnerable
      time of growth and development, and is recognized as one of the most significant
      chronic gastrointestinal diseases to affect children. Children and adolescents
      with IBD are at increased risk of complications as a result of malnutrition
      secondary to reduced appetite, increased metabolism and decreased absorptive
      capacity. The most common and serious complications are growth failure, bone
      demineralization and impaired psychosocial development. These issues add to the
      complexity of childhood IBD management and it is essential that adequate medical
      management is in place to prevent these long-term complications. Current
      treatment options include 5-aminosalicylic acid, antibiotics, corticosteroids,
      nutritional therapy and immunomodulators used to induce and maintain remission;
      some are specifically employed to maintain a steroid free long-term remission. As
      a general rule, long-term corticosteroid use should be avoided to reduce the risk
      of bone demineralization and growth failure. Newer treatment options such as
      infliximab have been shown to be effective for inducing and prolonging remission
      of Crohn's disease in children and paediatric use of infliximab is likely to
      increase in the near future. A recent case report, involving a 15-year old boy
      presenting with abdominal pain and bloody diarrhoea, illustrates the difficulty
      in correctly diagnosing IBD in children and the need for optimizing therapy to
      achieve treatment success.

PMID- 16594960
TI  - New lessons: classic treatments, expanding options in ulcerative colitis.
AB  - Ulcerative colitis (UC) of moderate severity is a common presentation in
      gastroenterological practice and a number of treatment options exist to rapidly
      and effectively induce remission. This review highlights how novel formulations
      and dosing regimens can ensure treatment success at a greater convenience for the
      patient with no increased risk of adverse effects. 5-aminosalicyclic acid (5-ASA)
      is well tolerated with a low incidence of adverse effects, and has a significant
      role in the management of UC. Different formulations of oral 5-ASA are now
      available and allow targeted treatment to inflammatory areas of the small bowel
      and ascending colon. 5-ASA is often initiated at a low dose for patients with
      mild to moderately active UC and with increasing doses for those who fail or have
      a poor response. 5-ASA at high doses is increasingly being used as induction
      therapy for active UC, particularly in patients with recurrent and/or extensive
      disease. The recent ASCEND studies show that an induction dose of 5-ASA of 4.8 g
      daily in patients with moderate UC is significantly more effective and resolves
      symptoms faster compared with a daily dose of 2.4 g. The evidence provided by the
      ASCEND studies support the rationale for a 'top-down' dosing strategy for UC
      where more potent therapies are introduced at an earlier stage of moderately
      severe disease.

PMID- 16594961
TI  - New thinking: theory vs practice. A case study illustrating evidence-based
      therapeutic decision making.
AB  - Evidence-based medicine (EBM) plays a key role for decision making in clinical
      practice. Clinicians are encouraged to adhere to treatment guidelines based on
      high quality clinical trials, systematic reviews and meta-analyses, that are the
      focus of the Cochrane Collaboration. EBM is not, however, a panacea for medical
      decision making. The results of randomized clinical trials apply to populations
      of patients, and the challenge is to translate the results to individuals.
      Individual patients require different thought processes because presentation and
      response vary, and external factors (e.g. patient preference) influence the
      choice of treatment. The application of EBM demands clinical judgement. The case
      of a 28 year old scientist who presented with typical features of moderate
      ulcerative colitis, illustrates the dilemma. At each stage of his illness the
      treatment options based on EBM were discussed, including high dose 5
      aminosalicyclic acid with or without topical therapy, corticosteroids,
      infliximab, immunomodulation, complementary therapy and surgery. Ultimately,
      therapeutic decisions depended on the patient's circumstances, preferences and
      response. Decisions should avoid circular motion caused by the illusion of
      progress and always consider the direction of travel.

PMID- 16594962
TI  - Bacteriophage replication modules.
AB  - Bacteriophages (prokaryotic viruses) are favourite model systems to study DNA
      replication in prokaryotes, and provide examples for every theoretically possible
      replication mechanism. In addition, the elucidation of the intricate interplay of
      phage-encoded replication factors with 'host' factors has always advanced the
      understanding of DNA replication in general. Here we review bacteriophage
      replication based on the long-standing observation that in most known phage
      genomes the replication genes are arranged as modules. This allows us to discuss
      established model systems--f1/fd, phiX174, P2, P4, lambda, SPP1, N15, phi29, T7
      and T4--along with those numerous phages that have been sequenced but not studied
      experimentally. The review of bacteriophage replication mechanisms and modules is
      accompanied by a compendium of replication origins and replication/recombination
      proteins (available as supplementary material online).

PMID- 16594963
TI  - The structures of Escherichia coli O-polysaccharide antigens.
AB  - Escherichia coli is usually a non-pathogenic member of the human colonic flora.
      However, certain strains have acquired virulence factors and may cause a variety
      of infections in humans and in animals. There are three clinical syndromes caused
      by E. coli: (i) sepsis/meningitis; (ii) urinary tract infection and (iii)
      diarrhoea. Furthermore the E. coli causing diarrhoea is divided into different
      'pathotypes' depending on the type of disease, i.e. (i) enterotoxigenic; (ii)
      enteropathogenic; (iii) enteroinvasive; (iv) enterohaemorrhagic; (v)
      enteroaggregative and (vi) diffusely adherent. The serotyping of E. coli based on
      the somatic (O), flagellar (H) and capsular polysaccharide antigens (K) is used
      in epidemiology. The different antigens may be unique for a particular serogroup
      or antigenic determinants may be shared, resulting in cross-reactions with other
      serogroups of E. coli or even with other members of the family Enterobacteriacea.
      To establish the uniqueness of a particular serogroup or to identify the presence
      of common epitopes, a database of the structures of O-antigenic polysaccharides
      has been created. The E. coli database (ECODAB) contains structures, nuclear
      magnetic resonance chemical shifts and to some extent cross-reactivity
      relationships. All fields are searchable. A ranking is produced based on
      similarity, which facilitates rapid identification of strains that are difficult
      to serotype (if known) based on classical agglutinating methods. In addition,
      results pertinent to the biosynthesis of the repeating units of O-antigens are
      discussed. The ECODAB is accessible to the scientific community at
      http://www.casper.organ.su.se/ECODAB/.

PMID- 16594964
TI  - Probiotics in marine larviculture.
AB  - Owing to the problem of antibiotic resistance and subsequent reluctance of using
      antibiotics, the use of probiotics in larviculture is becoming increasingly
      popular. During the early stages of development, manipulation of the larval
      digestive system seems possible through the addition of probiotics either through
      the culture water or via the livefood. Well-studied probiotics used in human
      medicine and terrestrial agriculture have proved to be successful in aquaculture
      and therefore reduce the need for extensive biosafety trials. The selection of
      probiotics requires various in vitro screening experiments, which assay for the
      production of antagonist compounds, their growth in and attachment to fish
      intestinal mucus, and the production of other beneficial compounds such as
      vitamins, fatty acids and digestive enzymes. Further information regarding
      probiont suitability can be obtained from its identification, interaction with
      livefood and host pathogenicity. Finally, pilot-scale in vivo tests need be
      performed, after which a production cost-benefit analysis to determine its
      economic viability needs to be undertaken.

PMID- 16594965
TI  - Microbial degradation of organophosphorus compounds.
AB  - Synthetic organophosphorus compounds are used as pesticides, plasticizers, air
      fuel ingredients and chemical warfare agents. Organophosphorus compounds are the
      most widely used insecticides, accounting for an estimated 34% of world-wide
      insecticide sales. Contamination of soil from pesticides as a result of their
      bulk handling at the farmyard or following application in the field or accidental
      release may lead occasionally to contamination of surface and ground water.
      Several reports suggest that a wide range of water and terrestrial ecosystems may
      be contaminated with organophosphorus compounds. These compounds possess high
      mammalian toxicity and it is therefore essential to remove them from the
      environments. In addition, about 200,000 metric tons of nerve (chemical warfare)
      agents have to be destroyed world-wide under Chemical Weapons Convention (1993).
      Bioremediation can offer an efficient and cheap option for decontamination of
      polluted ecosystems and destruction of nerve agents. The first micro-organism
      that could degrade organophosphorus compounds was isolated in 1973 and identified
      as Flavobacterium sp. Since then several bacterial and a few fungal species have
      been isolated which can degrade a wide range of organophosphorus compounds in
      liquid cultures and soil systems. The biochemistry of organophosphorus compound
      degradation by most of the bacteria seems to be identical, in which a
      structurally similar enzyme called organophosphate hydrolase or
      phosphotriesterase catalyzes the first step of the degradation. organophosphate
      hydrolase encoding gene opd (organophosphate degrading) gene has been isolated
      from geographically different regions and taxonomically different species. This
      gene has been sequenced, cloned in different organisms, and altered for better
      activity and stability. Recently, genes with similar function but different
      sequences have also been isolated and characterized. Engineered microorganisms
      have been tested for their ability to degrade different organophosphorus
      pollutants, including nerve agents. In this article, we review and propose
      pathways for degradation of some organophosphorus compounds by microorganisms.
      Isolation, characterization, utilization and manipulation of the major
      detoxifying enzymes and the molecular basis of degradation are discussed. The
      major achievements and technological advancements towards bioremediation of
      organophosphorus compounds, limitations of available technologies and future
      challenge are also discussed.

PMID- 16594966
TI  - Non-invasive microelectrode ion flux measurements to study adaptive responses of
      microorganisms to the environment.
AB  - The regulation of membrane-transport activity is crucial for intracellular pH
      homeostasis, maintenance of cell osmotic potential, nutrient acquisition,
      signalling, and adaptation of bacterial cells. The non-invasive microelectrode
      ion flux estimation (MIFE) technique is a powerful tool for kinetic studies of
      membrane-transport processes across cellular membranes. Since 2001, when this
      technique was first applied to the study of membrane-transport processes in
      bacterial cells (J Microbiol Methods 46, 119-129), a large amount of information
      has been accumulated. This review summarizes some of these findings and discusses
      the advantages and applicability of this technique in studying bacterial adaptive
      responses to adverse environmental conditions. First, various methodological
      aspects of the application of this novel technique in microbiology are discussed.
      Then, several practical examples ('case studies') are described. The latter
      include changes in membrane-transport activity in response to various stresses
      (acidic, osmotic, and temperature stresses) as well as flux changes as a function
      of bacterial growth stage and nutrient availability. It is shown that non
      invasive ion flux measurements may provide a significant conceptual advance in
      our understanding of adaptive responses in bacteria, fungi and biofilms to a
      variety of environmental conditions. The technique can also be used for the rapid
      assessment of food-processing treatments aimed at reducing bacterial
      contamination of food and for the development of strategies to assess the
      resistance of organisms to antimicrobial agents.

PMID- 16594967
TI  - Medecins sans Frontieres under the spotlight.

PMID- 16594968
TI  - Justified commitments? Considering resource allocation and fairness in Medecins
      sans Frontieres-Holland.
AB  - Non-governmental aid programs are an important source of health care for many
      people in the developing world. Despite the central role non-governmental
      organizations (NGOs) play in the delivery of these vital services, for the most
      part they either lack formal systems of accountability to their recipients
      altogether, or have only very weak requirements in this regard. This is because
      most NGOs are both self-mandating and self-regulating. What is needed in terms of
      accountability is some means by which all the relevant stakeholders can have
      their interests represented and considered. An ideally accountable decision
      making process for NGOs should identify acceptable justifications and rule out
      unacceptable ones. Thus, the point of this paper is to evaluate three prominent
      types of justification given for decisions taken at the Dutch headquarters of
      Medecins sans Frontieres. They are: population health justifications, mandate
      based justifications and advocacy-based justifications. The central question at
      issue is whether these justifications are sufficiently robust to answer the
      concerns and objections that various stakeholders may have. I am particularly
      concerned with the legitimacy these justifications have in the eyes of project
      beneficiaries. I argue that special responsibilities to certain communities can
      arise out of long-term engagement with them, but that this type of priority needs
      to be constrained such that it does not exclude other potential beneficiaries to
      an undesirable extent. Finally, I suggest several new institutional mechanisms
      that would enhance the overall equity of decisions and so would ultimately
      contribute to the legitimacy of the organization as a whole.

PMID- 16594969
TI  - Is it ethical to study what ought not to happen?
AB  - In the Democratic Republic of Congo, only an estimated 2% of all AIDS patients
      have access to treatment. As AIDS treatment access is scaled-up in the coming
      years, difficult rationing decisions will have to be made concerning who will
      come to gain access to this scarce medical resource. This article focuses on the
      position, expressed by representatives of Medecins sans Frontieres (MSF), that
      the practice of AIDS treatment access rationing is fundamentally unethical
      because it conflicts with the ideal of universal treatment access and the human
      right to health. The conclusion is that MSF's position lacks coherence, has
      negative practical implications, and is unfair to governments struggling to
      increase patient's access to AIDS treatment in unfavorable circumstances.

PMID- 16594970
TI  - Do aid agencies have an ethical duty to comply with researchers? A response to
      Rennie.
AB  - Medical AID organisations such as Medecins Sans Frontieres receive several
      requests from individuals and international academic institutions to conduct
      research at their implementation sites in Africa. Do AID agencies have an ethical
      duty to comply with research requests? In this paper we respond to the views and
      constructed theories (albeit unfounded) of one such researcher, whose request to
      conduct research at one of our sites in the Democratic Republic of Congo was
      turned down.

PMID- 16594971
TI  - Ethical considerations for clinical photography in the global South.
AB  - Clinical photography is an important tool for teaching practitioners and field
      workers about the clinical manifestations of famine and undernutrition,
      particularly with respect to the Global South. Current international guidelines
      for clinical photography are not consistently applied or enforced, which has led
      to violations of privacy and rights, particularly for patients and victims of
      disaster in the Global South. Combining existing clinical photography guidelines
      from the North with ongoing clinical ethics debates in the South, this paper
      explores approaches to establishing photography guidelines throughout the world
      that will be sensitive to the privacy and dignities of all patients and victims
      of emergencies.

PMID- 16594972
TI  - Ethics of care and HIV: a case for rural women in India.
AB  - Recent literature shows that ethics of care can be used as a theoretical basis to
      add a new, important dimension to social issues. This paper argues for a similar
      extension of the theoretical support from ethics of care to an area in bioethics.
      Specifically, it contends that a justification based ethics of care can be
      constructed to argue for a moral obligation to give some priority in the HIV
      related initiatives to one of most vulnerable groups; namely, the rural women in
      India. In an epidemic situation this care-based approach has certain advantages
      as a moral justification over the usual traditional approaches.

PMID- 16594973
TI  - Descriptive ethics: a qualitative study of local research ethics committees in
      Mexico.
AB  - OBJECTIVE: To describe how local research ethics committees (LRECs) consider and
      apply research ethics in the evaluation of biomedical research proposals. DESIGN:
      A qualitative study was conducted using purposeful sampling, focus groups and a
      grounded theory approach to generate data and to analyse the work of the LRECs.
      SETTING AND PARTICIPANTS: 11 LRECs of the Mexican Institute of Social Security
      (IMSS). RESULTS: LRECs considered ethics to be implicit in all types of research,
      but that ethics reviews were only necessary for projects that included the direct
      participation of human beings. The LRECs appeared to understand the importance of
      consent, as in the completion of a consent form, but did not emphasise the
      importance of the process of acquiring 'informed' consent. The committees
      considered their main roles or functions to be: (a) to improve the methodological
      quality of research and to verify - if applicable - the ethical aspects; (b) to
      encourage personnel to undergo research training; (c) to follow-up research to
      oversee the adherence to norms and compliance with a specified research
      timetable. CONCLUSIONS: This study provides a valuable insight into how these
      LRECs understand the ethical review process. The emphasis of the committees was
      on rules, regulations, improving research methodology and research training,
      rather than a focus on efforts to protect the rights and well being of research
      subjects. The results encourage further normative and descriptive lines of
      investigation concerning education and the development of LRECs.

PMID- 16594974
TI  - Strengthening medical ethics by strategic planning in the Islamic Republic of
      Iran.
AB  - To bring attention to medical ethics and to enhance the quality of health care in
      Iran, the Ministry of Health and Medical Education has introduced a strategic
      plan for medical ethics at a national level. This plan was developed through the
      organization and running of workshops in which experts addressed important areas
      related to medical ethics. They analysed strengths and weaknesses, opportunities
      and threats, and outlined a vision, a mission and specific goals and essential
      activities surrounding medical ethics. The current strategic plan has six main
      goals that will be reviewed in this paper. Some major activities that were
      carried out in recent years, and some future plans, will be also reviewed.

PMID- 16594975
TI  - Early genomics of learning and memory: a review.
AB  - The characterization of the molecular mechanisms whereby our brain codes, stores
      and retrieves memories remains a fundamental puzzle in neuroscience. Despite the
      knowledge that memory storage involves gene induction, the identification and
      characterization of the effector genes has remained elusive. The completion of
      the Human Genome Project and a variety of new technologies are revolutionizing
      the way these mechanisms can be explored. This review will examine how a genomic
      approach can be used to dissect and analyze the complex dynamic interactions
      involved in gene regulation during learning and memory. This innovative approach
      is providing information on a new class of genes associated with learning and
      memory in health and disease and is elucidating new molecular targets and
      pathways whose pharmacological modulation may allow new therapeutic approaches
      for improving cognition.

PMID- 16594976
TI  - Gravitaxis in Drosophila melanogaster: a forward genetic screen.
AB  - Perception of the earth's gravitational force is essential for most forms of
      animal life. However, little is known of the molecular mechanisms and neuronal
      circuitry underlying gravitational responses. A forward genetic screen using
      Drosophila melanogaster that provides insight into these characteristics is
      described here. Vertical choice mazes combined with additional behavioral assays
      were used to identify mutants specifically affected in gravitaxic responses.
      Twenty-three mutants were selected for molecular analysis. As a result, 18
      candidate genes are now implicated in the gravitaxic behavior of flies. Many of
      these genes have orthologs across the animal kingdom, while some are more
      specific to Drosophila and invertebrates. One gene (yuri) located close to a
      known locus for gravitaxis has been the subject of more extensive analysis
      including confirmation by transgenic rescue.

PMID- 16594977
TI  - The genetic contribution to canine personality.
AB  - The domestic dog may be exceptionally well suited for behavioral genetic studies
      owing to its population history and the striking behavior differences among
      breeds. To explore to what extent and how behavioral traits are transmitted
      between generations, heritabilities and genetic correlations for behavioral
      traits were estimated in a cohort containing over 10,000 behaviorally tested
      German shepherd and Rottweiler dogs. In both breeds, the pattern of co
      inheritance was found to be similar for the 16 examined behavioral traits.
      Furthermore, over 50% of the additive genetic variation of the behavioral traits
      could be explained by one underlying principal component, indicating a shared
      genetic component behind most of the examined behavioral traits. Only aggression
      appears to be inherited independently of the other traits. The results support a
      genetic basis for a broad personality trait previously named shyness-boldness
      dimension, and heritability was estimated to be 0.25 in the two breeds.
      Therefore, breeds of dogs appear to constitute a valuable resource for behavioral
      genetic research on the normal behavioral differences in broad personality
      traits.

PMID- 16594978
TI  - Progressive cognitive decline in a transgenic mouse model of Alzheimer's disease
      overexpressing mutant hAPPswe.
AB  - The possibility of detecting progressive changes in cognitive function reflecting
      the spatio-temporal pattern of beta-amyloid peptide (Abeta) deposition was
      investigated in Tg2576 mice overexpressing the human mutant amyloid precursor
      protein (hAPP). Here, we show that at 7 months of age, Tg2576 mice exhibited a
      selective deficit in hippocampus-based operations including a defective
      habituation of object exploration, a lack of reactivity to spatial novelty and a
      disruption of allothetic orientation in a cross-shaped maze. At 14 months of age,
      Tg2576 mice displayed a more extended pattern of behavioral abnormalities,
      because they failed to react to object novelty and exclusively relied on motor
      based orientation in the cross-shaped maze. However, an impaired reactivity to
      spatial and object novelty possibly reflecting age-related attention deficits
      also emerged in aged wild-type mice. These findings further underline that early
      cognitive markers of AD can be detected in Tg2576 mice before Abeta deposition
      occurs and suggest that as in humans, cognitive deterioration progressively
      evolves from an initial hippocampal syndrome to global dementia because of the
      combined effect of the neuropathology and aging.

PMID- 16594979
TI  - Sp1 and NFkappaB pathways are regulated in brain in response to acute and chronic
      ethanol.
AB  - DNA microarray analysis was used to identify candidate ethanol-regulated genes,
      as a first step towards exploring how transcriptional changes might lead to
      ethanol-induced changes in behaviour. Mice were treated with a single acute
      intraperitoneal ethanol dose and DNA microarray analysis performed on midbrain 2
      h posttreatment. We predicted that if ethanol-regulated genes contribute towards
      behaviour, then constitutive variation in brain expression levels may also
      contribute to strain-specific differences in ethanol-related behaviour of inbred
      mouse strains. On the basis of this assumption, we interrogated the BXD inbred
      strain phenotype database and the U74Av2 MAS5 brain expression database using the
      WebQTL tool (http://www.genenetwork.org/) and correlated ethanol-related
      behaviours to expression levels. Constitutive expression levels of 70/90
      candidate genes, identified from the DNA microarray analysis, varied
      significantly between inbred strains and correlated significantly with strain
      specific differences in ethanol-related behaviours. These genes were then mapped
      onto biochemical pathways using Stratagene's PathwayAssist software. This
      analysis identified the transcription factor Sp1 and NFkappaB pathways in the
      acute response to ethanol. Ethanol regulation of Sp1 transcription was conserved
      between humans and mouse. As predicted, downstream targets of Sp1 were also
      ethanol regulated. NFkappaBia, an important regulator of NFkappaB function and
      Rela, an NFkappaB-binding partner, were both regulated by ethanol. Expression of
      both Sp1 and NFkappaBialpha were also downregulated following chronic ethanol
      treatment. As Sp1 and NFkappaB are implicated in plasticity and behaviour, our
      data suggest a role for these transcription factors in the long-term behavioural
      adaptations to ethanol.

PMID- 16594980
TI  - Maternal behavior deficits in nulliparous oxytocin knockout mice.
AB  - The first observations of postpartum oxytocin knockout (OTKO) mice found no
      maternal behavior deficits. However, it is unclear how detailed those
      observations were. In this study, we compared maternal behavior exhibited by OTKO
      and wild-type (WT) nullipara toward six 2-4-day-old foster pups during test
      sessions conducted on 3 successive days. Each day, subjects were placed in a
      clean cage 30 min prior to introduction of pups which were deposited in a clump
      adjacent to the middle of a long wall of each test cage. Behavior was measured
      for 3.5 h after which pups and test subjects were returned to their home cages.
      On test days 1 and 3, a significantly smaller proportion of OTKO females
      retrieved pups to a corner of their cage. Also, significantly fewer pups were
      retrieved to corners by OTKO females. In contrast to most WTs, most OTKO females
      mothered pups in the center of the cage where they were initially deposited. Pup
      licking frequencies were significantly lower in OTKO females. Their self-grooming
      frequencies also trended toward being lower. Latencies to retrieve and lick pups,
      latencies to and frequencies of still crouching over pups and proportion of time
      in nest did not differ between groups. Our findings suggest that OT stimulates a
      significant proportion of pup-licking in nulliparous mice, a situation similar to
      lactating rat mothers. Our results also indicate that OT may play a role in the
      motivation to retrieve pups to a more secure location.

PMID- 16594981
TI  - Transgenic mice expressing a human mutant beta1 thyroid receptor are hyperactive,
      impulsive, and inattentive.
AB  - Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed
      childhood psychiatric disorder. We have found that a transgenic mouse bearing a
      human mutant thyroid receptor (TRbeta1) expresses all of the defining symptoms of
      ADHD--inattention, hyperactivity, and impulsivity--as well as a 'paradoxical'
      response to methylphenidate (MPH). As with ADHD, the behavioral phenotypes
      expressed by the TRbeta transgenic mice are dynamic and sensitive to changes in
      environmental conditions, stress, and reinforcement. TRbeta transgenic mice are
      euthyroid except for a brief period during postnatal development, but the
      behavioral phenotypes, elevated dopamine turnover, and paradoxical response to
      MPH persist into adulthood. Thus, like the vast majority of children with ADHD,
      the TRbeta transgenic mice exhibit the symptoms of ADHD in the complete absence
      of thyroid abnormalities. This suggests that even transient perturbations in
      developmental thyroid homeostasis can have long-lasting behavioral and cognitive
      consequences, including producing the full spectrum of symptoms of ADHD.

PMID- 16594983
TI  - Of mice and men--cross-species digit ratio (2D:4D) research: comment on Bailey,
      Wahlsten and Hurd (2005).

PMID- 16594987
TI  - New horizons: NT-proBNP for risk stratification of patients with shock in the
      intensive care unit.
AB  - B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) are
      promising cardiac biomarkers that have recently been shown to be of diagnostic
      value in decompensated heart failure, acute coronary syndromes and other
      conditions resulting in myocardial stretch and volume overload. In view of the
      high prevalence of cardiac disorders in the intensive care unit, the experience
      of elevated natriuretic peptide levels in the critically ill might be of enormous
      diagnostic and therapeutic value. BNP and NT-proBNP levels rise to different
      degrees in critical illness and may also serve as markers of severity and
      prognosis in diseases beyond acute or chronic heart failure. The diagnostic and
      prognostic use of natriuretic peptides in the intensive care setting for patients
      with various forms of shock could be an attractive alternative as noninvasive
      markers of cardiac dysfunction that could obviate the need for pulmonary artery
      catheterization in some patients.

PMID- 16594986
TI  - RNA editing of human microRNAs.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short RNAs of around 22 nucleotides that
      regulate gene expression. The primary transcripts of miRNAs contain double
      stranded RNA and are therefore potential substrates for adenosine to inosine (A
      to-I) RNA editing. RESULTS: We have conducted a survey of RNA editing of miRNAs
      from ten human tissues by sequence comparison of PCR products derived from
      matched genomic DNA and total cDNA from the same individual. Six out of 99 (6%)
      miRNA transcripts from which data were obtained were subject to A-to-I editing in
      at least one tissue. Four out of seven edited adenosines were in the mature miRNA
      and were predicted to change the target sites in 3' untranslated regions. For a
      further six miRNAs, we identified A-to-I editing of transcripts derived from the
      opposite strand of the genome to the annotated miRNA. These miRNAs may have been
      annotated to the wrong genomic strand. CONCLUSION: Our results indicate that RNA
      editing increases the diversity of miRNAs and their targets, and hence may
      modulate miRNA function.

PMID- 16594988
TI  - Skin microcirculation and vasopressin infusion: a laser Doppler study.
AB  - Use of arginine vasopressin in the management of refractory vasodilatory shock
      has been associated with development of ischaemic skin lesions. Because of the
      increasing popularity of arginine vasopressin, it is important to evaluate its
      effects on microcirculatory blood flow. Such studies are crucial if we are to
      appreciate the microcirculatory consequences of our various resuscitation
      strategies. However, methodological issues must always be considered because they
      can significantly influence interpretation of the results. Some aspects of use of
      laser Doppler to evaluate the microcirculation are reviewed within the context of
      recent findings presented by Luckner and coworkers in this issue of Critical
      Care.

PMID- 16594989
TI  - Muscle dissatisfaction in young adult men.
AB  - BACKGROUND: Appearance concerns are of increasing importance in young men's
      lives. We investigated whether muscle dissatisfaction is associated with
      psychological symptoms, dietary supplement or anabolic steroid use, or physical
      activity in young men. METHODS: As a part of a questionnaire assessment of health
      related behaviors in the population-based FinnTwin16 study, we assessed factors
      associated with muscle dissatisfaction in 1245 men aged 22-27 using logistic
      regression models. RESULTS: Of men, 30% experienced high muscle dissatisfaction,
      while 12% used supplements/steroids. Of highly muscle-dissatisfied men, 21.5%
      used supplements/steroids. Mean body mass index, waist circumference, or leisure
      aerobic activity index did not differ between individuals with high/low muscle
      dissatisfaction. Muscle dissatisfaction was significantly associated with a
      psychological and psychosomatic problems, alcohol and drug use, lower height
      satisfaction, sedentary lifestyle, poor subjective physical fitness, and lower
      life satisfaction. CONCLUSION: Muscle dissatisfaction and supplement/steroid use
      are relatively common, and are associated with psychological distress and markers
      of sedentary lifestyle.

PMID- 16594990
TI  - Identification of DNA sequence variation in Campylobacter jejuni strains
      associated with the Guillain-Barre syndrome by high-throughput AFLP analysis.
AB  - BACKGROUND: Campylobacter jejuni is the predominant cause of antecedent infection
      in post-infectious neuropathies such as the Guillain-Barre (GBS) and Miller
      Fisher syndromes (MFS). GBS and MFS are probably induced by molecular mimicry
      between human gangliosides and bacterial lipo-oligosaccharides (LOS). This study
      describes a new C. jejuni-specific high-throughput AFLP (htAFLP) approach for
      detection and identification of DNA polymorphism, in general, and of putative
      GBS/MFS-markers, in particular. RESULTS: We compared 6 different isolates of the
      "genome strain" NCTC 11168 obtained from different laboratories. HtAFLP analysis
      generated approximately 3000 markers per stain, 19 of which were polymorphic. The
      DNA polymorphisms could not be confirmed by PCR-RFLP analysis, suggesting a
      baseline level of 0.6% AFLP artefacts. Comparison of NCTC 11168 with 4 GBS
      associated strains revealed 23 potentially GBS-specific markers, 17 of which were
      identified by DNA sequencing. A collection of 27 GBS/MFS-associated and 17
      enteritis control strains was analyzed with PCR-RFLP tests based on 11 of these
      markers. We identified 3 markers, located in the LOS biosynthesis genes cj1136,
      cj1138 and cj1139c, that were significantly associated with GBS (P = 0.024, P =
      0.047 and P < 0.001, respectively). HtAFLP analysis of 13 highly clonal South
      African GBS/MFS-associated and enteritis control strains did not reveal GBS
      specific markers. CONCLUSION: This study shows that bacterial GBS markers are
      limited in number and located in the LOS biosynthesis genes, which corroborates
      the current consensus that LOS mimicry may be the prime etiologic determinant of
      GBS. Furthermore, our results demonstrate that htAFLP, with its high
      reproducibility and resolution, is an effective technique for the detection and
      subsequent identification of putative bacterial disease markers.

PMID- 16594991
TI  - Bio++: a set of C++ libraries for sequence analysis, phylogenetics, molecular
      evolution and population genetics.
AB  - BACKGROUND: A large number of bioinformatics applications in the fields of bio
      sequence analysis, molecular evolution and population genetics typically share
      input/output methods, data storage requirements and data analysis algorithms.
      Such common features may be conveniently bundled into re-usable libraries, which
      enable the rapid development of new methods and robust applications. RESULTS: We
      present Bio++, a set of Object Oriented libraries written in C++. Available
      components include classes for data storage and handling (nucleotide/amino
      acid/codon sequences, trees, distance matrices, population genetics datasets),
      various input/output formats, basic sequence manipulation (concatenation,
      transcription, translation, etc.), phylogenetic analysis (maximum parsimony,
      markov models, distance methods, likelihood computation and maximization),
      population genetics/genomics (diversity statistics, neutrality tests, various
      multi-locus analyses) and various algorithms for numerical calculus. CONCLUSION:
      Implementation of methods aims at being both efficient and user-friendly. A
      special concern was given to the library design to enable easy extension and new
      methods development. We defined a general hierarchy of classes that allow the
      developer to implement its own algorithms while remaining compatible with the
      rest of the libraries. Bio++ source code is distributed free of charge under the
      CeCILL general public licence from its website http://kimura.univ
      montp2.fr/BioPP.

PMID- 16594993
TI  - Handwriting performance in the absence of visual control in writer's cramp
      patients: initial observations.
AB  - BACKGROUND: The present study was aimed at investigating the writing parameters
      of writer's cramp patients and control subjects during handwriting of a test
      sentence in the absence of visual control. METHODS: Eight right-handed patients
      with writer's cramp and eight healthy volunteers as age-matched control subjects
      participated in the study. The experimental task consisted in writing a test
      sentence repeatedly for fifty times on a pressure-sensitive digital board. The
      subject did not have visual control on his handwriting. The writing performance
      was stored on a PC and analyzed off-line. RESULTS: During handwriting all
      patients developed a typical dystonic limb posture and reported an increase in
      muscular tension along the experimental session. The patients were significantly
      slower than the controls, with lower mean vertical pressure of the pen tip on the
      paper and they could not reach the endmost letter of the sentence in the given
      time window. No other handwriting parameter differences were found between the
      two groups. CONCLUSION: Our findings indicate that during writing in the absence
      of visual feedback writer's cramp patients are slower and could not reach the
      endmost letter of the test sentence, but their level of automatization is not
      impaired and writer's cramp handwriting parameters are similar to those of the
      controls except for even lower vertical pressure of the pen tip on the paper,
      which is probably due to a changed strategy in such experimental conditions.

PMID- 16594992
TI  - ALK1 signalling analysis identifies angiogenesis related genes and reveals
      disparity between TGF-beta and constitutively active receptor induced gene
      expression.
AB  - BACKGROUND: TGF-beta1 is an important angiogenic factor involved in the different
      aspects of angiogenesis and vessel maintenance. TGF-beta signalling is mediated
      by the TbetaRII/ALK5 receptor complex activating the Smad2/Smad3 pathway. In
      endothelial cells TGF-beta utilizes a second type I receptor, ALK1, activating
      the Smad1/Smad5 pathway. Consequently, a perturbance of ALK1, ALK5 or TbetaRII
      activity leads to vascular defects. Mutations in ALK1 cause the vascular disorder
      hereditary hemorrhagic telangiectasia (HHT). METHODS: The identification of ALK1
      and not ALK5 regulated genes in endothelial cells, might help to better
      understand the development of HHT. Therefore, the human microvascular endothelial
      cell line HMEC-1 was infected with a recombinant constitutively active ALK1
      adenovirus, and gene expression was studied by using gene arrays and quantitative
      real-time PCR analysis. RESULTS: After 24 hours, 34 genes were identified to be
      up-regulated by ALK1 signalling. Analysing ALK1 regulated gene expression after 4
      hours revealed 13 genes to be up- and 2 to be down-regulated. Several of these
      genes, including IL-8, ET-1, ID1, HPTPeta and TEAD4 are reported to be involved
      in angiogenesis. Evaluation of ALK1 regulated gene expression in different human
      endothelial cell types was not in complete agreement. Further on, disparity
      between constitutively active ALK1 and TGF-beta1 induced gene expression in HMEC
      1 cells and primary HUVECs was observed. CONCLUSION: Gene array analysis
      identified 49 genes to be regulated by ALK1 signalling and at least 14 genes are
      reported to be involved in angiogenesis. There was substantial agreement between
      the gene array and quantitative real-time PCR data. The angiogenesis related
      genes might be potential HHT modifier genes. In addition, the results suggest
      endothelial cell type specific ALK1 and TGF-beta signalling.

PMID- 16594994
TI  - A del(X)(p11) carrying SRY sequences in an infant with ambiguous genitalia.
AB  - BACKGROUND: SRY (sex-determining region, Y) is the gene responsible of gonadal
      differentiation in the male and it is essential for the regular development of
      male genitalia. Translocations involving the human sex chromosomes are rarely
      reported, however here we are reporting a very rare translocation of SRY gene to
      the q -arm of a deleted X chromosome. This finding was confirmed by cytogenetic,
      fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR).
      CASE PRESENTATION: A 7-month infant was clinically diagnosed as an intersex case,
      with a phallus, labia majora and minora, a blind vagina and a male urethra.
      Neither uterus nor testes was detected by Ultrasonography. G-banding of his
      chromosomes showed 46,X,del(X)(p11) and fluorescent in situ hybridization (FISH)
      analysis showed a very small piece from the Y chromosome translocated to the q
      arm of the del(X). Polymerase chain reaction (PCR) analysis revealed the presence
      of material from the sex-determining region Y (SRY) gene. CONCLUSION: It is
      suggested that the phenotype of the patient was caused by activation of the
      deleted X chromosome with SRY translocation, which is responsible for gonadal
      differentiation.

PMID- 16594995
TI  - Spontaneous internal desynchronization of locomotor activity and body temperature
      rhythms from plasma melatonin rhythm in rats exposed to constant dim light.
AB  - BACKGROUND: We have recently reported that spontaneous internal desynchronization
      between the locomotor activity rhythm and the melatonin rhythm may occur in rats
      (30% of tested animals) when they are maintained in constant dim red light
      (LLdim) for 60 days. Previous work has also shown that melatonin plays an
      important role in the modulation of the circadian rhythms of running wheel
      activity (Rw) and body temperature (Tb). The aim of the present study was to
      investigate the effect that desynchronization of the melatonin rhythm may have on
      the coupling and expression of circadian rhythms in Rw and Tb. METHODS: Rats were
      maintained in a temperature controlled (23-24 degrees C) ventilated lightproof
      room under LLdim (red dim light 1 microW/cm2 [5 Lux], lower wavelength cutoff at
      640 nm). Animals were individually housed in cages equipped with a running wheel
      and a magnetic sensor system to detect wheel rotation; Tb was monitored by
      telemetry. Tb and Rw data were recorded in 5-min bins and saved on disk. For each
      animal, we determined the mesor and the amplitude of the Rw and Tb rhythm using
      waveform analysis on 7-day segments of the data. After sixty days of LLdim
      exposure, blood samples (80-100 microM) were collected every 4 hours over a 24
      hrs period from the tail artery, and serum melatonin levels were measured by
      radioimmunoassay. RESULTS: Twenty-one animals showed clear circadian rhythms Rw
      and Tb, whereas one animal was arrhythmic. Rw and Tb rhythms were always strictly
      associated and we did not observe desynchronization between these two rhythms.
      Plasma melatonin levels showed marked variations among individuals in the peak
      levels and in the night-to-day ratio. In six rats, the night-to-day ratio was
      less than 2, whereas in the rat that showed arrhythmicity in Rw and Tb melatonin
      levels were high and rhythmic with a large night-to-day ratio. In seven animals,
      serum melatonin levels peaked during the subjective day (from CT0 to CT8), thus
      suggesting that in these animals the circadian rhythm of serum melatonin
      desynchronized from the circadian rhythms of Rw and Tb. No significant
      correlation was observed between the amplitude (or the levels) of the melatonin
      profile and the amplitude and mesor of the Rw and Tb rhythms. CONCLUSION: Our
      data indicate that the free-running periods (tau) and the amplitude of Rw and Tb
      were not different between desynchronized and non-desynchronized rats, thus
      suggesting that the circadian rhythm of serum melatonin plays a marginal role in
      the regulation of the Rw and Tb rhythms. The present study also supports the
      notion that in the rat the circadian rhythms of locomotor activity and body
      temperature are controlled by a single circadian pacemaker.

PMID- 16594996
TI  - Patients with femoral or distal forearm fracture in Germany: a prospective
      observational study on health care situation and outcome.
AB  - BACKGROUND: Distal radius and proximal femoral fractures are typical injuries in
      later life, predominantly due to simple falls, but modulated by other relevant
      factors such as osteoporosis. Fracture incidence rates rise with age. Because of
      the growing proportion of elderly people in Western industrialized societies, the
      number of these fractures can be expected to increase further in the coming
      years, and with it the burden on healthcare resources. Our study therefore
      assessed the effects of these injuries on the health status of older people over
      time. The purpose of this paper is to describe the study method, clinical
      parameters of fracture patients during hospitalization, mortality up to one and a
      half years after discharge in relation to various factors such as type of
      fracture, and to describe changes in mobility and living situation. METHODS: Data
      were collected from all consecutive patients (no age limit) admitted to 423
      hospitals throughout Germany with distal radius or femoral fractures (57% acute
      care, femoral and forearm fractures; 43% rehabilitation, femoral fractures only)
      between January 2002 and September 2003. Polytrauma and coma patients were
      excluded. Demographic characteristics, exact fracture location, mobility and
      living situation, clinical and laboratory parameters were examined. Current
      health status was assessed in telephone interviews conducted on average 6-7
      months after discharge. Where telephone contact could not be established, at
      least survival status (living/deceased/date of death) was determined. RESULTS:
      The study population consisted of 12,520 femoral fracture patients (86.8% hip
      fractures), average age 77.5 years, 76.5% female, and 2,031 forearm fracture
      patients, average age 67.6 years, 81.6% female. Women's average age was 6.6
      (femoral fracture) to 10 years (forearm fracture) older than men's (p < 0.0001).
      Only 4.6% of femoral fracture patients experienced changes in their living
      situation post-discharge (53% because of the fracture event), although less than
      half of subjects who were able to walk without assistive devices prior to the
      fracture event (76.7%) could still do so at time of interview (34.9%). At time of
      interview, 1.5% of subjects were bed-ridden (0.2% before fracture). Forearm
      fracture patients reported no change in living situation at all. Of the femoral
      fracture patients 119 (0.95%), and of the forearm fracture patients 3 (0.15%)
      died during hospital stay. Post-discharge (follow-up one and a half years) 1,463
      femoral fracture patients died (19.2% acute-care patients, 8.5% rehabilitation
      patients), but only 60 forearm fracture patients (3.0%). Ninety percent of
      femoral fracture deaths happened within the first year, approximately 66% within
      the first 6 months. More acute-care patients with a pertrochanteric fracture died
      within one year post-discharge (20.6%) than patients with a cervical fracture
      (16.1%). CONCLUSION: Mortality after proximal femoral fracture is still
      alarmingly high and highest after pertrochanteric fracture. Although at time of
      interview more than half of femoral fracture patients reported reduced mobility,
      most patients (96%) attempt to live at home. Since forearm fracture patients were
      on average 10 years younger than femoral fracture patients, forearm fractures may
      be a means of diagnosing an increased risk of later hip fractures.

PMID- 16594997
TI  - Interleukin-1beta and anaphylatoxins exert a synergistic effect on NGF expression
      by astrocytes.
AB  - C3a and C5a anaphylatoxins are proinflammatory polypeptides released during
      complement activation. They exert their biological activities through interaction
      with two G protein-coupled receptors named C3aR and C5aR, respectively. In the
      brain, these receptors are expressed on glial cells, and some recent data have
      suggested that anaphylatoxins could mediate neuroprotection. In this study, we
      used RT-PCR and ribonuclease protection assays (RPA) to investigate the role of
      anaphylatoxins on neurotrophin expression by the human glioblastoma cell line
      T98G and by rat astrocytes. Our data show that for both cell types,
      anaphylatoxins upregulate expression of NGF mRNA. This response depended on a G
      protein-coupled pathway since pre-treatment of cells with pertussis toxin (PTX)
      completely blocked NGF mRNA increases. This effect was anaphylatoxin-specific
      since pre-incubation with anti-C3a or anti-C5aR antibodies abolished the effects
      of C3a and C5a, respectively. The regulation of NGF mRNA by anaphylatoxins was
      not accompanied by translation into protein expression, but there was a
      significant synergic effect of anaphylatoxins/IL-1b costimulation. Our
      demonstration of involvement of anaphylatoxins in the NGF release process by
      astrocytes suggests that C3a and C5a could modulate neuronal survival in the CNS.

PMID- 16594998
TI  - An online database for brain disease research.
AB  - BACKGROUND: The Stanley Medical Research Institute online genomics database
      (SMRIDB) is a comprehensive web-based system for understanding the genetic
      effects of human brain disease (i.e. bipolar, schizophrenia, and depression).
      This database contains fully annotated clinical metadata and gene expression
      patterns generated within 12 controlled studies across 6 different microarray
      platforms. DESCRIPTION: A thorough collection of gene expression summaries are
      provided, inclusive of patient demographics, disease subclasses, regulated
      biological pathways, and functional classifications. CONCLUSION: The combination
      of database content, structure, and query speed offers researchers an efficient
      tool for data mining of brain disease complete with information such as: cross
      platform comparisons, biomarkers elucidation for target discovery, and
      lifestyle/demographic associations to brain diseases.

PMID- 16594999
TI  - Application of real-time PCR to quantify hepatitis B virus DNA in chronic
      carriers in The Gambia.
AB  - BACKGROUND/AIM: The study aimed at developing a real-time quantitative PCR assay
      to monitor HBV serum virus load of chronic carriers enrolled in therapeutic
      trials. METHOD: Quantitative real-time PCR assay was carried out using SYBR-Green
      signal detection and primers specific to the S gene. Thermal cycling was
      performed in an ABi 5700 sequence detection system. The assay was calibrated
      against an international HBV DNA standard and inter- and intra-assay
      reproducibility determined. Levels of viral load were monitored for 1-year in
      lamivudine treated carriers. Correlation between HBV DNA levels and HBeAg sero
      status was determined in untreated carriers. RESULTS: The qPCR assay showed good
      intra- and inter-assay reproducibility over a wide dynamic range (1.5 x 103 to
      1.5 x 108 copies/mL) and correlated well with those from a commercial assay (r =
      0.91, (p < 0.001). Viral load levels dropped dramatically but temporarily during
      and after a short course of lamivudine therapy. HBV DNA was a more reliable
      indicator of the presence of virus than HBe antigen and was detected in 77.0%
      (161/209) of HBeAg negative and in all HBeAg positive carriers. CONCLUSION: This
      method is reliable, accurate, and reproducible. HBV DNA Quantification by qPCR
      can be used to monitor the efficacy of HBV therapy and useful in understanding
      the natural history of HBV in an endemic area.

PMID- 16595000
TI  - Effects of abciximab on key pattern of human coronary restenosis in vitro: impact
      of the SI/MPL-ratio.
AB  - BACKGROUND: The significant reduction of angiographic restenosis rates in the
      ISAR-SWEET study (intracoronary stenting and antithrombotic regimen: is abciximab
      a superior way to eliminate elevated thrombotic risk in diabetes) raises the
      question of whether abciximab acts on clopidogrel-independent mechanisms in
      suppressing neointimal hyperplasia. The current study investigates the direct
      effect of abciximab on ICAM-1 expression, migration and proliferation. METHODS:
      ICAM-1: Part I of the study investigates in cytoflow studies the effect of
      abciximab (0.0002, 0.002, 0.02, 0.2, 2.0, and 20.0 microg/ml) on TNF-alpha
      induced expression of intercellular adhesion molecule 1 (ICAM-1). Migration: Part
      II of the study explored the effect of abciximab (0.0002, 0.002, 0.02, 0.2, 2.0,
      and 20.0 microg/ml) on migration of HCMSMC over a period of 24 h. Proliferation:
      Part III of the study investigated the effect of abciximab (0.0002, 0.002, 0.02,
      0.2, 2.0, and 20.0 microg/ml) on proliferation of HUVEC, HCAEC, and HCMSMC after
      an incubation period of 5 days. RESULTS: ICAM-1: In human venous endothelial
      cells (HUVEC), human coronary endothelial cells (HCAEC) and human coronary medial
      smooth muscle cells (HCMSMC) no inhibitory or stimulatory effect on expression of
      ICAM-1 was detected. Migration: After incubation of HCMSMC with abciximab in
      concentrations of 0.0002-2 microg/ml a stimulatory effect on cell migration was
      detected, statistical significance was achieved after incubation with 0.002
      microg/ml (p < 0.05), 0.002 microg/ml (p < 0.001), and 0.2 microg/ml (p < 0.05).
      Proliferation: Small but statistically significant antiproliferative effects of
      abciximab were detected after incubation of HUVEC (0.02 and 2.0 microg/ml; p =
      0.01 and p < 0.01), HCAEC (2.0 and 20.0 microg/ml; p < 0.05 and p < 0,01), and
      HCMSMC (2.0 and 20.0 microg/ml; p < 0.05 and p < 0.05). The significant
      inhibition (SI) of cell proliferation found in HCAEC and HCMSMC was achieved with
      drug concentrations more than 10 times beyond the maximal plasma level (MPL),
      resulting in a SI/MPL-ratio > 1. CONCLUSION: Thus, the anti-restenotic effects of
      systemically administered abciximab reported in the ISAR-SWEET-study were not
      caused by a direct inhibitory effect on ICAM-1 expression, migration or
      proliferation.

PMID- 16595001
TI  - Predicting the subcellular localization of viral proteins within a mammalian host
      cell.
AB  - BACKGROUND: The bioinformatic prediction of protein subcellular localization has
      been extensively studied for prokaryotic and eukaryotic organisms. However, this
      is not the case for viruses whose proteins are often involved in extensive
      interactions at various subcellular localizations with host proteins. RESULTS:
      Here, we investigate the extent of utilization of human cellular localization
      mechanisms by viral proteins and we demonstrate that appropriate eukaryotic
      subcellular localization predictors can be used to predict viral protein
      localization within the host cell. CONCLUSION: Such predictions provide a method
      to rapidly annotate viral proteomes with subcellular localization information.
      They are likely to have widespread applications both in the study of the
      functions of viral proteins in the host cell and in the design of antiviral
      drugs.

PMID- 16595003
TI  - A randomized cross over trial of tolerability and compliance of a micronutrient
      supplement with low iron separated from calcium vs high iron combined with
      calcium in pregnant women [ISRCTN56071145].
AB  - BACKGROUND: Prenatal micronutrient combinations with high iron content are
      associated with high rates of gastrointestinal symptoms. This coupled with nausea
      and vomiting of pregnancy results in women often discontinuing their
      multivitamins. A new prescription supplement (PregVit) that separates iron from
      calcium in two tablets--morning and evening, has lower elemental iron content (35
      mg), but results in similar extent of iron absorption when compared to another
      supplement containing (60 mg) of elemental iron (Materna). The objectives of this
      study were to compare tolerability and compliance with PregVit vs. a supplement
      with high iron content (Materna), in pregnant women. METHODS: Randomized,
      crossover open labeled study in 135 pregnant women attending outpatient clinics
      in Ontario and Quebec. RESULTS: Use of PregVit was associated with a 30%
      reduction in constipation rate as compared to Materna. Both products demonstrated
      similar compliance rates. Compliance of Materna was negatively associated with
      the severity of nausea and vomiting of pregnancy. No such correlation was found
      for PregVvit. CONCLUSION: PregVit, a supplement with lower iron content (35 mg),
      has significantly decreased constipation rates as compared to 60 mg iron--Materna
      and has similar compliance rates. High iron content in multivitamin supplements
      is associated with adverse effects in pregnancy.

PMID- 16595002
TI  - What effect does physician "profiling" have on inpatient physician satisfaction
      and hospital length of stay?
AB  - BACKGROUND: 2002 marked the first time that the rate of hospital spending in the
      United States out-paced the overall health care spending rate of growth since
      1991. As hospital spending continues to grow and as reimbursement for hospital
      expenses has moved towards the prospective payment system, there is still
      increasing pressure to reduce costs. Hospitals have a major incentive to decrease
      resource utilization, including hospital length of stay. We evaluated whether
      physician profiling affects physician satisfaction and hospital length of stay,
      and assessed physicians' views concerning hospital cost containment and the
      quality of care they provide. METHODS: To determine if physician profiling
      affects hospital length of stay and/or physician satisfaction, we used quasi
      experimental with before-versus-after and intervention-versus-control comparisons
      of length of stay data collected at an intervention and six control hospitals.
      Intervention hospital physicians were informed their length of stay would be
      compared to their peers and were given a questionnaire assessing their
      experience. RESULTS: Nearly half of attending pre-profiled physicians felt
      negative about the possibility of being profiled, while less than one-third of
      profiled physicians reported feeling negative about having been profiled. Nearly
      all physicians greatly enjoyed their ward month. Length of stay at the profiled
      site decreased by an additional 1/3 of a day in the profiling year, compared to
      the non-profiled sites (p < 0.001). CONCLUSION: A relatively non-instrusive
      profiling intervention modestly reduced length of stay without adversely
      affecting physician satisfaction.

PMID- 16595004
TI  - Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant
      human prostate tissues.
AB  - BACKGROUND: In prostate cancer, normal citrate-producing glandular secretory
      epithelial cells undergo a metabolic transformation to malignant citrate
      oxidizing cells. m-Aconitase is the critical step involved in this altered
      citrate metabolism that is essential to prostate malignancy. The limiting m
      aconitase activity in prostate epithelial cells could be the result of a
      decreased level of m-aconitase enzyme and/or the inhibition of existing m
      aconitase. Earlier studies identified zinc as an inhibitor of m-aconitase
      activity in prostate cells; and that the depletion of zinc in malignant cells is
      an important factor in this metabolic transformation. However, a possibility
      remains that an altered expression and level of m-aconitase enzyme might also be
      involved in this metabolic transformation. To address this issue, the in situ
      level of m-aconitase enzyme was determined by immunohistochemical analysis of
      prostate cancer tissue sections and malignant prostate cell lines. RESULTS: The
      immunocytochemical procedure successfully identified the presence of m-aconitase
      localized in the mitochondrial compartment in PC-3, LNCaP, and DU-145 malignant
      prostate cell lines. The examination of prostate tissue sections from prostate
      cancer subjects demonstrated that m-aconitase enzyme is present in the glandular
      epithelium of normal glands, hyperplastic glands, adenocrcinomatous glands, and
      prostatic intraepithelial neoplastic foci. Quantitative analysis of the relative
      level of m-aconitase in the glandular epithelium of citrate-producing adenomatous
      glands versus the citrate-oxidizing adenocarcinomatous glands revealed no
      significant difference in m-aconitase enzyme levels. This is in contrast to the
      down-regulation of ZIP1 zinc transporter in the malignant glands versus
      hyperplastic glands that exists in the same tissue samples. CONCLUSION: The
      results demonstrate the existence of m-aconitase enzyme in the citrate-producing
      glandular epithelial cells; so that deficient m-aconitase enzyme is not
      associated with the limiting m-aconitase activity that prevents citrate oxidation
      in these cells. The level of m-aconitase is maintained in the malignant cells; so
      that an altered enzyme level is not associated with the increased m-aconitase
      activity. Consequently, the elevated zinc level that inhibits m-aconitase enzyme
      is responsible for the impaired citrate oxidation in normal and hyperplastic
      prostate glandular epithelial cells. Moreover, the down-regulation of ZIP1 zinc
      transporter and corresponding depletion of zinc results in the increase in the
      activity of the existing m-aconitase activity in the malignant prostate cells.
      The studies now define the mechanism for the metabolic transformation that
      characterizes the essential transition of normal citrate-producing epithelial
      cells to malignant citrate-oxidizing cells.

PMID- 16595005
TI  - Traumatic events, PTSD, and psychiatric comorbidity in forensic patients-
      assessed by questionnaires and diagnostic interview.
AB  - BACKGROUND: Relationships between posttraumatic stress disorder (PTSD), comorbid
      illness and experiences of traumatic stressors have been reported for large and
      different groups. The present study investigated this relationship specifically
      for patients with psychiatric disorders admitted to a forensic ward because of
      criminal behavior. METHODS: In sixteen German and fifteen Sudanese forensic
      patients the prevalence of PTSD and comorbid symptoms of anxiety and depression
      were assessed and related to traumatic experiences, emotional distress, and
      stressful life events over four developmental periods. RESULTS: In the total
      sample, subjects had experienced an average of five traumatic events, the first
      one occurring early in childhood, and 39% met criteria of current, 55% of
      lifetime PTSD, the diagnosis being more likely in patients with a greater number
      of reported traumatic experiences. Neglect and emotional abuse in childhood were
      associated with current PTSD diagnosis. As reported for other populations,
      comorbid symptoms were frequent with 60% of the sample displaying comorbid
      anxiety symptoms and 64% comorbid depression. PTSD and comorbidity did not differ
      between cultures. CONCLUSION: Results suggest that forensic patients experience
      multiple traumatic events, usually beginning early in development, so that the
      assessment of PTSD and comorbid anxiety and depression is recommended for the
      clinical evaluation. Further studies have to substantiate, whether traumatic
      stress during developmental stages interact with other factors leading to routes
      of forensic psychopathology.

PMID- 16595006
TI  - Cardiac dysfunction in the diabetic rat: quantitative evaluation using high
      resolution magnetic resonance imaging.
AB  - BACKGROUND: Diabetes is a major risk factor for cardiovascular disease. In
      particular, type 1 diabetes compromises the cardiac function of individuals at a
      relatively early age due to the protracted course of abnormal glucose
      homeostasis. The functional abnormalities of diabetic myocardium have been
      attributed to the pathological changes of diabetic cardiomyopathy. METHODS: In
      this study, we used high field magnetic resonance imaging (MRI) to evaluate the
      left ventricular functional characteristics of streptozotocin treated diabetic
      Sprague-Dawley rats (8 weeks disease duration) in comparison with age/sex matched
      controls. RESULTS: Our analyses of EKG gated cardiac MRI scans of the left
      ventricle showed a 28% decrease in the end-diastolic volume and 10% increase in
      the end-systolic volume of diabetic hearts compared to controls. Mean stroke
      volume and ejection fraction in diabetic rats were decreased (48% and 28%,
      respectively) compared to controls. Further, dV/dt changes were suggestive of
      phase sensitive differences in left ventricular kinetics across the cardiac cycle
      between diabetic and control rats. CONCLUSION: Thus, the MRI analyses of diabetic
      left ventricle suggest impairment of diastolic and systolic hemodynamics in this
      rat model of diabetic cardiomyopathy. Our studies also show that in vivo MRI
      could be used in the evaluation of cardiac dysfunction in this rat model of type
      1 diabetes.

PMID- 16595007
TI  - A systems approach to clinical oncology: focus on breast cancer.
AB  - During the past decade, genomic microarrays have been applied with some success
      to the molecular profiling of breast tumours, which has resulted in a much more
      detailed classification scheme as well as in the identification of potential gene
      signature sets. These gene sets have been applied to both the prognosis and
      prediction of outcome to treatment and have performed better than the current
      clinical criteria. One of the main limitations of microarray analysis, however,
      is that frozen tumour samples are required for the assay. This imposes severe
      limitations on access to samples and precludes large scale validation studies
      from being conducted. Quantitative reverse transcriptase polymerase chain
      reaction (qRT-PCR), on the other hand, can be used with degraded RNAs derived
      from formalin-fixed paraffin-embedded (FFPE) tumour samples, the most important
      and abundant source of clinical material available. More recently, the novel DASL
      (cDNA-mediated Annealing, Selection, extension and Ligation) assay has been
      developed as a high throughput gene expression profiling system specifically
      designed for use with FFPE tumour tissue samples.However, we do not believe that
      genomics is adequate as a sole prognostic and predictive platform in breast
      cancer. The key proteins driving oncogenesis, for example, can undergo post
      translational modifications; moreover, if we are ever to move individualization
      of therapy into the practical world of blood-based assays, serum proteomics
      becomes critical. Proteomic platforms, including tissue micro-arrays (TMA) and
      protein chip arrays, in conjunction with surface-enhanced laser desorption
      ionization time-of-flight mass spectrometry (SELDI-TOF/MS), have been the
      technologies most widely applied to the characterization of tumours and serum
      from breast cancer patients, with still limited but encouraging results. This
      review will focus on these genomic and proteomic platforms, with an emphasis
      placed on the utilization of FFPE tumour tissue samples and serum, as they have
      been applied to the study of breast cancer for the discovery of gene signatures
      and biomarkers for the early diagnosis, prognosis and prediction of treatment
      outcome. The ultimate goal is to be able to apply a systems biology approach to
      the information gleaned from the combination of these techniques in order to
      select the best treatment strategy, monitor its effectiveness and make changes as
      rapidly as possible where needed to achieve the optimal therapeutic results for
      the patient.

PMID- 16595008
TI  - La cuerda dulce--a tolerability and acceptability study of a novel approach to
      specimen collection for diagnosis of paediatric pulmonary tuberculosis.
AB  - BACKGROUND: Recent data demonstrate the utility of the string test for the
      diagnosis of sputum-scarce HIV-associated TB in adults. We hypothesized that, if
      well-tolerated by children, this simple tool might offer a breakthrough in
      paediatric TB diagnosis. Thus the objective of this study, undertaken in the
      paediatric service of the Hospital Nacional Dos de Mayo, Lima, Peru, was to
      determine the tolerability and acceptability of the string test to paediatric TB
      suspects, their parents and nursing staff. METHODS: 22 paediatric subjects aged 3
      14 years (median 8) under investigation for TB were invited to undergo 2 string
      tests (four-hour downtime each). Subjective and objective pain and discomfort
      rating scales were used to assess the perception of the subject, parent and
      attending nurse. RESULTS: Patients as young as 4 years tolerated the procedure
      extremely well with 84% willing to undergo a second procedure. Peak discomfort at
      the time of swallowing and of string retrieval was mild (30% of maximum possible
      score) and brief as judged by visual analogue ratings and objective indicators.
      Good concordance of parent/child and objective/subjective ratings strengthened
      the validity of these findings. CONCLUSION: The string test is well tolerated and
      achievable for most paediatric TB suspects as young as 4 years. A formal
      prospective paediatric efficacy study is now needed.

PMID- 16595009
TI  - Comparative maturation of cynomolgus monkey oocytes in vivo and in vitro.
AB  - BACKGROUND: In vitro maturation (IVM) of oocytes followed by fertilization in
      vitro (IVF) and embryo transfer offers an alternative to conventional IVF
      treatment that minimises drug administration and avoids ovarian hyperstimulation.
      However, the technique is less efficient than maturation in vivo. In the present
      study, a non-human primate model was used to address the hypothesis that the
      number of oocytes is increased and their nuclear and cytoplasmic maturity after
      IVM are improved when maturation is initiated in vivo by priming with hCG.
      METHODS: Young, adult cynomolgus monkeys were given recombinant human (rh)
      gonadotropins to stimulate the development of multiple follicles, and oocytes
      were aspirated 0, 12, 24, or 36 h after injection of an ovulatory dose of rhCG.
      The nuclear status of oocytes was determined at the time of recovery and after
      culture for a total elapsed time of 40-44 hours after hCG. RESULTS: Priming with
      hCG significantly increased the number of oocytes harvested, especially after
      delaying aspiration for 24 h or longer. Nuclear maturation after the full period
      in culture was also enhanced by priming: 71.5, 83.6, and 94.6% of oocytes
      collected at 0, 12, and 24 h hCG had progressed to MII by the end of the culture
      period, compared to 87.8% of oocytes that were retrieved at 36 h. A large
      proportion of oocytes reaching the MII stage had either or both abnormal spindles
      (>40%) and misaligned chromosomes (>60%), judging by immunofluorescence
      microscopy, but these abnormalities were independent of culture time. The
      mitochondria were evenly distributed throughout the cytoplasm at all stages of
      maturation. Importantly, there was no microscopic evidence that the duration of
      culture had any injurious effects on the cells. CONCLUSION: In conclusion, the
      evidence supports this non-human primate as a model for human IVM and the
      practice of priming with hCG to promote developmental potential.

PMID- 16595010
TI  - Cotranscription and intergenic splicing of the PPARG and TSEN2 genes in cattle.
AB  - BACKGROUND: Intergenic splicing resulting in the combination of mRNAs sequences
      from distinct genes is a newly identified mechanism likely to contribute to
      protein diversity. Few cases have been described, most of them involving
      neighboring genes and thus suggesting a cotranscription event presumably due to
      transcriptional termination bypass. RESULTS: We identified bovine chimeric
      transcripts resulting from cotranscription and intergenic splicing of two
      neighboring genes, PPARG and TSEN2. These two genes encode the Peroxisome
      Proliferator Activated Receptors gamma1 and gamma2 and the tRNA Splicing
      Endonuclease 2 homolog and are situated in the same orientation about 50 kb apart
      on bovine chromosome 22q24. Their relative position is conserved in human and
      mouse. We identified two types of chimeric transcripts containing all but the
      last exon of the PPARG gene followed by all but the first exon of the TSEN2 gene.
      The two chimers differ by the presence/absence of an intermediate exon resulting
      from transcription of a LINE L2 sequence situated between the two genes. Both
      transcripts use canonical splice sites for all exons coming from both genes, as
      well as for the LINE L2 sequence. One of these transcripts harbors a premature
      STOP codon and the other encodes a putative chimeric protein combining most of
      the PPARgamma protein and the entire TSEN2 protein, but we could not establish
      the existence of this protein. CONCLUSION: By showing that both individual and
      chimeric transcripts are transcribed from PPARG and TSEN2, we demonstrated
      regulation of transcription termination. Further, the existence and functionality
      of a chimeric protein harboring active motifs that are a priori unrelated is
      hypothesized.

PMID- 16595011
TI  - The effect of posterior subtenon methylprednisolone acetate in the refractory
      diabetic macular edema: a prospective nonrandomized interventional case series.
AB  - BACKGROUND: To investigate the efficacy of posterior subtenon methylprednisolone
      acetate injection in treatment of refractory diffuse clinically significant
      diabetic macular edema (CSME). METHODS: In a prospective, nonrandomized,
      interventional case series, 52 eyes were diagnosed with CSME and treated with at
      least two sessions of laser photocoagulation according to Early Treatment
      Diabetic Retinopathy Study guidelines. At least 3 months after laser therapy,
      eyes with a residual central macular thickness were offered posterior subtenon
      injection of 40 mg methylprednisolone acetate. Main outcome measures were visual
      acuity, macular thickness and intraocular pressure. Potential complications were
      monitored, including intraocular pressure response, cataract progression and
      scleral perforation. RESULTS: Mean baseline visual acuity (in logMAR) improved
      significantly (p = 0.003) from 0.8 +/- 0.36 to 0.6 +/- 0.41 at 3 months. Mean
      foveal thickness decreased from 388 +/- 78 mum at baseline to 231 +/- 40 mum
      after 3 months (p < 0.0001). Visual acuity improvement in eyes with CSME with
      extrafoveal hard exudates was significant (p = 0.0001), but not significant in
      eyes with CSME with subfoveal hard exudates (p = 0.32). Intraocular pressure
      increased from 14.7 +/- 2.0 mmHg (range, 12-18 mmHg) to a maximum value of 15.9
      +/- 2.1 mmHg (range, 12-20 mmHg) during the follow-up period. Complications in
      two eyes developed focal conjunctival necrosis at the site of injection.
      CONCLUSION: Posterior subtenon methylprednisolone acetate may improve early
      visual outcome in diffuse diabetic macular edema that fails to respond to
      conventional laser photocoagulation. Visual acuity improvement in eyes with CSME
      with extrafoveal hard exudates was significant; and this improvement is depends
      on location of hard exudates. Further study is needed to assess the long-term
      efficacy, safety, and retreatment.

PMID- 16595012
TI  - NIDDK data repository: a central collection of clinical trial data.
AB  - BACKGROUND: The National Institute of Diabetes and Digestive and Kidney Diseases
      have established central repositories for the collection of DNA, biological
      samples, and clinical data to be catalogued at a single site. Here we present an
      overview of the site which stores the clinical data and links to biospecimens.
      DESCRIPTION: The NIDDK Data repository is a web-enabled resource cataloguing
      clinical trial data and supporting information from NIDDK supported studies. The
      Data Repository allows for the co-location of multiple electronic datasets that
      were created as part of clinical investigations. The Data Repository does not
      serve the role of a Data Coordinating Center, but rather as a warehouse for the
      clinical findings once the trials have been completed. Because both biological
      and genetic samples are collected from many of the studies, a data management
      system for the cataloguing and retrieval of samples was developed. CONCLUSION:
      The Data Repository provides a unique resource for researchers in the clinical
      areas supported by NIDDK. In addition to providing a warehouse of data, Data
      Repository staff work with the users to educate them on the datasets as well as
      assist them in the acquisition of multiple data sets for cross-study analysis.
      Unlike the majority of biological databases, the Data Repository acts both as a
      catalogue for data, biosamples, and genetic materials and as a central processing
      point for the requests for all biospecimens. Due to regulations on the use of
      clinical data, the ultimate release of that data is governed under NIDDK data
      release policies. The Data Repository serves as the conduit for such requests.

PMID- 16595014
TI  - A comparison of alternative 60-mer probe designs in an in-situ synthesized
      oligonucleotide microarray.
AB  - BACKGROUND: DNA microarrays have proven powerful for functional genomics studies.
      Several technologies exist for the generation of whole-genome arrays. It is well
      documented that 25mer probes directed against different regions of the same gene
      produce variable signal intensity values. However, the extent to which this is
      true for probes of greater length (60mers) is not well characterized. Moreover,
      this information has not previously been reported for whole-genome arrays
      designed against bacteria, whose genomes may differ substantially in
      characteristics directly affecting microarray performance. RESULTS: We report
      here an analysis of alternative 60mer probe designs for an in-situ synthesized
      oligonucleotide array for the GC rich, beta-proteobacterium Burkholderia
      cenocepacia. Probes were designed using the ArrayOligoSel3.5 software package and
      whole-genome microarrays synthesized by Agilent, Inc. using their in-situ, ink
      jet technology platform. We first validated the quality of the microarrays as
      demonstrated by an average signal to noise ratio of >1000. Next, we determined
      that the variance of replicate probes (1178 total probes examined) of identical
      sequence was 3.8% whereas the variance of alternative probes (558 total
      alternative probes examined) designs was 9.5%. We determined that depending upon
      the definition, about 2.4% of replicate and 7.8% of alternative probes produced
      outlier conclusions. Finally, we determined none of the probe design subscores
      (GC content, internal repeat, binding energy and self annealment) produced by
      ArrayOligoSel3.5 were predictive or probes that produced outlier signals.
      CONCLUSION: Our analysis demonstrated that the use of multiple probes per target
      sequence is not essential for in-situ synthesized 60mer oligonucleotide arrays
      designed against bacteria. Although probes producing outlier signals were
      identified, the use of ratios results in less than 10% of such outlier
      conclusions. We also determined that several different measures commonly utilized
      in probe design were not predictive of outlier probes.

PMID- 16595013
TI  - Predictors of opioid misuse in patients with chronic pain: a prospective cohort
      study.
AB  - BACKGROUND: Opioid misuse can complicate chronic pain management, and the non
      medical use of opioids is a growing public health problem. The incidence and risk
      factors for opioid misuse in patients with chronic pain, however, have not been
      well characterized. We conducted a prospective cohort study to determine the one
      year incidence and predictors of opioid misuse among patients enrolled in a
      chronic pain disease management program within an academic internal medicine
      practice. METHODS: One-hundred and ninety-six opioid-treated patients with
      chronic, non-cancer pain of at least three months duration were monitored for
      opioid misuse at pre-defined intervals. Opioid misuse was defined as: 1. Negative
      urine toxicological screen (UTS) for prescribed opioids; 2. UTS positive for
      opioids or controlled substances not prescribed by our practice; 3. Evidence of
      procurement of opioids from multiple providers; 4. Diversion of opioids; 5.
      Prescription forgery; or 6. Stimulants (cocaine or amphetamines) on UTS. RESULTS:
      The mean patient age was 52 years, 55% were male, and 75% were white. Sixty-two
      of 196 (32%) patients committed opioid misuse. Detection of cocaine or
      amphetamines on UTS was the most common form of misuse (40.3% of misusers). In
      bivariate analysis, misusers were more likely than non-misusers to be younger (48
      years vs 54 years, p < 0.001), male (59.6% vs. 38%; p = 0.023), have past alcohol
      abuse (44% vs 23%; p = 0.004), past cocaine abuse (68% vs 21%; p < 0.001), or
      have a previous drug or DUI conviction (40% vs 11%; p < 0.001%). In multivariate
      analyses, age, past cocaine abuse (OR, 4.3), drug or DUI conviction (OR, 2.6),
      and a past alcohol abuse (OR, 2.6) persisted as predictors of misuse. Race,
      income, education, depression score, disability score, pain score, and literacy
      were not associated with misuse. No relationship between pain scores and misuse
      emerged. CONCLUSION: Opioid misuse occurred frequently in chronic pain patients
      in a pain management program within an academic primary care practice. Patients
      with a history of alcohol or cocaine abuse and alcohol or drug related
      convictions should be carefully evaluated and followed for signs of misuse if
      opioids are prescribed. Structured monitoring for opioid misuse can potentially
      ensure the appropriate use of opioids in chronic pain management and mitigate
      adverse public health effects of diversion.

PMID- 16595016
TI  - Absorbing and transferring risk: assessing the impact of a statewide high-risk
      pregnancy telemedical program on VLBW maternal transports.
AB  - BACKGROUND: Prior research has shown that resources have an impact on birth
      outcomes. In this paper we ask how combinations of telemedical and hospital-level
      resources impact transports of mothers expecting very low birth weight (VLBW)
      babies in Arkansas. METHODS: Using de-identified birth certificate data from the
      Arkansas Department of Health, data were gathered on transports of women carrying
      VLBW babies for two six-month periods: a period just before the start of ANGELS
      (12/02-05/03), a telemedical outreach program for high-risk pregnancies, and a
      period after the program had been running for six months (12/03-05/04). For each
      maternal transport, the following information was recorded: maternal race
      ethnicity, maternal age, and the birth weight of the infant. Logistic regression
      was used to assess the relationship between the predictors (telemedicine,
      hospital level, maternal characteristics) and the probability of a transport.
      RESULTS: Having a telemedical site available increases the probability of a
      mother carrying a VLBW baby being transported to a level III facility either
      before or during birth. Having at least a level II nursery also increases the
      chance of a maternal transport. Where both level II nurseries and telemedical
      access are available, the odds of VLBW maternal transports are only modestly
      increased in comparison to the case where neither is present. At the individual
      level, Hispanic mothers were less likely to be transported than other mothers,
      and teenaged mothers were more likely to be transported than those 18 and over. A
      mother's being Black or being over 35 did not have an impact on the odds of being
      transported to a level III facility. CONCLUSION: Combinations of resources have
      an impact on physician decisions regarding VLBW transports and are interpretable
      in terms of the capacity to diagnose and absorb risk. We suggest a collegial
      review of transport patterns and birth outcomes from areas with different levels
      of resources as a vehicle for moving the entire system of care forward over time.
      With such an evidence-based review in place, the collegial relations among level
      III specialists and obstetricians from around the state can, over time, develop
      workable protocols for when and how level III facilities should be involved.

PMID- 16595015
TI  - Inhalation of beta 2 agonists impairs the clearance of nontypable Haemophilus
      influenzae from the murine respiratory tract.
AB  - BACKGROUND: Nontypable Haemophilus influenzae (NTHi) is a common bacterial
      pathogen causing human respiratory tract infections under permissive conditions
      such as chronic obstructive pulmonary disease. Inhalation of beta2-receptor
      agonists is a widely used treatment in patients with chronic obstructive
      pulmonary disease. The aim of this study was to determine the effect of
      inhalation of beta2 agonists on the host immune response to respiratory tract
      infection with NTHi. METHODS: Mouse alveolar macrophages were stimulated in vitro
      with NTHi in the presence or absence of the beta2 receptor agonists salmeterol or
      salbutamol. In addition, mice received salmeterol or salbutamol by inhalation and
      were intranasally infected with NTHi. End points were pulmonary inflammation and
      bacterial loads. RESULTS: Both salmeterol and salbutamol inhibited NTHi induced
      tumor necrosis factor-alpha (TNFalpha) release by mouse alveolar macrophages in
      vitro by a beta receptor dependent mechanism. In line, inhalation of either
      salmeterol or salbutamol was associated with a reduced early TNFalpha production
      in lungs of mice infected intranasally with NTHi, an effect that was reversed by
      concurrent treatment with the beta blocker propranolol. The clearance of NTHi
      from the lungs was impaired in mice treated with salmeterol or salbutamol, an
      adverse effect that was prevented by propranolol and independent of the reduction
      in TNFalpha. CONCLUSION: These data suggest that inhalation of salmeterol or
      salbutamol may negatively influence an effective clearance of NTHi from the
      airways.

PMID- 16595017
TI  - A high-throughput screen identifying sequence and promiscuity characteristics of
      the loxP spacer region in Cre-mediated recombination.
AB  - BACKGROUND: Cre-loxP recombination refers to the process of site-specific
      recombination mediated by two loxP sequences and the Cre recombinase protein.
      Transgenic experiments exploit integrative recombination, where a donor plasmid
      carrying a loxP site and DNA of interest integrate into a recipient loxP site in
      a target genome. Unfortunately, integrative recombination is highly inefficient
      because the insert is flanked by two loxP sites, which themselves become targets
      for Cre and lead to subsequent excision of the insert. A small number of
      mutations have been discovered in parts of the loxP sequence, specifically the
      spacer and inverted repeat segments, that increase the efficiency of integrative
      recombination. In this study we introduce a high-throughput in vitro assay to
      rapidly detect novel loxP spacer mutants and describe the sequence
      characteristics of successful recombinants. RESULTS: We created synthetic loxP
      oligonucleotides that contained a combination of inverted repeat mutations (the
      lox66 and lox71 mutations) and mutant spacer sequences, degenerate at 6 of the 8
      positions. After in vitro Cre recombination, 3,124 recombinant clones were
      identified by sequencing. Included in this set were 31 unique, novel, self
      recombining sequences. Using network visualization tools, we recognized 12 spacer
      sets with restricted promiscuity. We observed that increased guanine content at
      all spacer positions save for position 8 resulted in increased recombination.
      Interestingly, recombination between identical spacers was not preferred over non
      identical spacers. We also identified a set of 16 pairs of loxP spacers that
      reacted at least twice with another spacer, but not themselves. Further, neither
      the wild-type P1 phage loxP sequence nor any of the known loxP spacer mutants
      appeared to be kinetically favoured by Cre recombinase. CONCLUSION: This study
      approached loxP spacer mutant screening in an unbiased manner, assuming nothing
      about candidate loxP sites save for the conserved 4 and 5 spacer positions.
      Candidate sites were free to recombine with any other sequence in the pool of all
      possible sites. The subset of loxP sites identified here are candidates for in
      vivo serial recombination as they have already demonstrated limited promiscuity
      with other loxP spacer and stability in the presence of Cre.

PMID- 16595018
TI  - The effect of web based depression interventions on self reported help seeking:
      randomised controlled trial [ISRCTN77824516].
AB  - BACKGROUND: To date, there has been very little work investigating behaviour
      changes induced by interventions that are designed to increase help seeking. The
      present paper examines the effects of two Internet depression websites on help
      seeking. METHODS: 414 individuals with elevated scores on a depression assessment
      scale were randomly allocated to a depression information website, a cognitive
      behavioural skills training website (CBT) or an attention control condition.
      Reports of help seeking for specific treatments, from specific sources and for
      categories of treatments were assessed. RESULTS: Relative to the control, the
      depression information site was associated with decreases in seeking support from
      friends and family, the use of music and of everyday treatments and no increase
      in seeking evidence based interventions. The CBT site was associated with the
      report of help seeking for CBT, massage and exercise. CONCLUSION: Methods to
      encourage the use of evidence-based treatments need further research to determine
      whether the assistance sought is evidence based and whether there are unintended
      effects.

PMID- 16595019
TI  - GAIA: an easy-to-use web-based application for interaction analysis of case
      control data.
AB  - BACKGROUND: The advent of cheap, large scale genotyping has led to widespread
      adoption of genetic association mapping as the tool of choice in the search for
      loci underlying susceptibility to common complex disease. Whilst simple single
      locus analysis is relatively trivial to conduct, this is not true of more complex
      analysis such as those involving interactions between loci. The importance of
      testing for interactions between loci in association analysis has been
      highlighted in a number of recent high profile publications. RESULTS: Genetic
      Association Interaction Analysis (GAIA) is a web-based application for testing
      for statistical interactions between loci. It is based upon the widely used case
      control study design for genetic association analysis and is designed so that non
      specialists may routinely apply tests for interaction. GAIA allows simple testing
      of both additive and additive plus dominance interaction models and includes
      permutation testing to appropriately correct for multiple testing. The
      application will find use both in candidate gene based studies and in genome-wide
      association studies. For large scale studies GAIA includes a screening approach
      which prioritizes loci (based on the significance of main effects at one or both
      loci) for further interaction analysis. CONCLUSION: GAIA is available at
      http://www.bbu.cf.ac.uk/html/research/biostats.htm.

PMID- 16595020
TI  - Genomic characterization of ribitol teichoic acid synthesis in Staphylococcus
      aureus: genes, genomic organization and gene duplication.
AB  - BACKGROUND: Staphylococcus aureus or MRSA (Methicillin Resistant S. aureus), is
      an acquired pathogen and the primary cause of nosocomial infections worldwide. In
      S. aureus, teichoic acid is an essential component of the cell wall, and its
      biosynthesis is not yet well characterized. Studies in Bacillus subtilis have
      discovered two different pathways of teichoic acid biosynthesis, in two strains
      W23 and 168 respectively, namely teichoic acid ribitol (tar) and teichoic acid
      glycerol (tag). The genes involved in these two pathways are also characterized,
      tarA, tarB, tarD, tarI, tarJ, tarK, tarL for the tar pathway, and tagA, tagB,
      tagD, tagE, tagF for the tag pathway. With the genome sequences of several MRSA
      strains: Mu50, MW2, N315, MRSA252, COL as well as methicillin susceptible strain
      MSSA476 available, a comparative genomic analysis was performed to characterize
      teichoic acid biosynthesis in these S. aureus strains. RESULTS: We identified all
      S. aureus tar and tag gene orthologs in the selected S. aureus strains which
      would contribute to teichoic acids sythesis. Based on our identification of genes
      orthologous to tarI, tarJ, tarL, which are specific to tar pathway in B. subtilis
      W23, we also concluded that tar is the major teichoic acid biogenesis pathway in
      S. aureus. Further analyses indicated that the S. aureus tar genes, different
      from the divergon organization in B. subtilis, are organized into several
      clusters in cis. Most interesting, compared with genes in B. subtilis tar
      pathway, the S. aureus tar specific genes (tarI,J,L) are duplicated in all six S.
      aureus genomes. CONCLUSION: In the S. aureus strains we analyzed, tar (teichoic
      acid ribitol) is the main teichoic acid biogenesis pathway. The tar genes are
      organized into several genomic groups in cis and the genes specific to tar
      (relative to tag): tarI, tarJ, tarL are duplicated. The genomic organization of
      the S. aureus tar pathway suggests their regulations are different when compared
      to B. subtilis tar or tag pathway, which are grouped in two operons in a divergon
      structure.

PMID- 16595021
TI  - Health care utilization among Medicare-Medicaid dual eligibles: a count data
      analysis.
AB  - BACKGROUND: Medicare-Medicaid dual eligibles are the beneficiaries of both
      Medicare and Medicaid. Dual eligibles satisfy the eligibility conditions for
      Medicare benefit. Dual eligibles also qualify for Medicaid because they are aged,
      blind, or disabled and meet the income and asset requirements for receiving
      Supplement Security Income (SSI) assistance. The objective of this study is to
      explore the relationship between dual eligibility and health care utilization
      among Medicare beneficiaries. METHODS: The household component of the nationally
      representative Medical Expenditure Panel Survey (MEPS) 1996-2000 is used for the
      analysis. Total 8,262 Medicare beneficiaries are selected from the MEPS data. The
      Medicare beneficiary sample includes individuals who are covered by Medicare and
      do not have private health insurance during a given year. Zero-inflated negative
      binomial (ZINB) regression model is used to analyse the count data regarding
      health care utilization: office-based physician visits, hospital inpatient
      nights, agency-sponsored home health provider days, and total dental visits.
      RESULTS: Dual eligibility is positively correlated with the likelihood of using
      hospital inpatient care and agency-sponsored home health services and the
      frequency of agency-sponsored home health days. Frequency of dental visits is
      inversely associated with dual eligibility. With respect to racial differences,
      dually eligible Afro-Americans use more office-based physician and dental
      services than white duals. Asian duals use more home health services than white
      duals at the 5% statistical significance level. The dual eligibility programs
      seem particularly beneficial to Afro-American duals. CONCLUSION: Dual eligibility
      has varied impact on health care utilization across service types. More
      utilization of home healthcare among dual eligibles appears to be the result of
      delayed realization of their unmet healthcare needs under the traditional
      Medicare-only program rather than the result of overutilization in response to
      the expanded benefits of the dual eligibility program. The dual eligibility
      program is particularly beneficial to Asian and Afro-American duals in
      association with the provision of home healthcare and dental benefits.

PMID- 16595022
TI  - Distinct short-range ovule signals attract or repel Arabidopsis thaliana pollen
      tubes in vitro.
AB  - BACKGROUND: Pollen tubes deliver sperm after navigating through flower tissues in
      response to attractive and repulsive cues. Genetic analyses in maize and
      Arabidopsis thaliana and cell ablation studies in Torenia fournieri have shown
      that the female gametophyte (the 7-celled haploid embryo sac within an ovule) and
      surrounding diploid tissues are essential for guiding pollen tubes to ovules. The
      variety and inaccessibility of these cells and tissues has made it challenging to
      characterize the sources of guidance signals and the dynamic responses they
      elicit in the pollen tubes. RESULTS: Here we developed an in vitro assay to study
      pollen tube guidance to excised A. thaliana ovules. Using this assay we discerned
      the temporal and spatial regulation and species-specificity of late stage
      guidance signals and characterized the dynamics of pollen tube responses. We
      established that unfertilized A. thaliana ovules emit diffusible, developmentally
      regulated, species-specific attractants, and demonstrated that ovules penetrated
      by pollen tubes rapidly release diffusible pollen tube repellents. CONCLUSION:
      These results demonstrate that in vitro pollen tube guidance to excised A.
      thaliana ovules efficiently recapitulates much of in vivo pollen tube behaviour
      during the final stages of pollen tube growth. This assay will aid in confirming
      the roles of candidate guidance molecules, exploring the phenotypes of A.
      thaliana pollen tube guidance mutants and characterizing interspecies pollination
      interactions.

PMID- 16595023
TI  - Performances and microbial features of an aerobic packed-bed biofilm reactor
      developed to post-treat an olive mill effluent from an anaerobic GAC reactor.
AB  - BACKGROUND: Olive mill wastewater (OMW) is the aqueous effluent of olive oil
      producing processes. Given its high COD and content of phenols, it has to be
      decontaminated before being discharged. Anaerobic digestion is one of the most
      promising treatment process for such an effluent, as it combines high
      decontamination efficiency with methane production. The large scale anaerobic
      digestion of OMWs is normally conducted in dispersed-growth reactors, where
      however are generally achieved unsatisfactory COD removal and methane production
      yields. The possibility of intensifying the performance of the process using a
      packed bed biofilm reactor, as anaerobic treatment alternative, was demonstrated.
      Even in this case, however, a post-treatment step is required to further reduce
      the COD. In this work, a biological post-treatment, consisting of an aerobic
      biological "Manville" silica bead-packed bed aerobic reactor, was developed,
      tested for its ability to complete COD removal from the anaerobic digestion
      effluents, and characterized biologically through molecular tools. RESULTS: The
      aerobic post-treatment was assessed through a 2 month-continuous feeding with the
      digested effluent at 50.42 and 2.04 gl(-1)day(-1) of COD and phenol loading
      rates, respectively. It was found to be a stable process, able to remove 24 and
      39% of such organic loads, respectively, and to account for 1/4 of the overall
      decontamination efficiency displayed by the anaerobic-aerobic integrated system
      when fed with an amended OMW at 31.74 and 1.70 gl(-1)day(-1) of COD and phenol
      loading rates, respectively. Analysis of 16S rRNA gene sequences of biomass
      samples from the aerobic reactor biofilm revealed that it was colonized by
      Rhodobacterales, Bacteroidales, Pseudomonadales, Enterobacteriales, Rhodocyclales
      and genera incertae sedis TM7. Some taxons occurring in the influent were not
      detected in the biofilm, whereas others, such as Paracoccus, Pseudomonas,
      Acinetobacter and Enterobacter, enriched significantly in the biofilter
      throughout the treatment. CONCLUSION: The silica-bead packed bed biofilm reactor
      developed and characterized in this study was able to significantly decontaminate
      anaerobically digested OMWs. Therefore, the application of an integrated
      anaerobic-aerobic process resulted in an improved system for valorization and
      decontamination of OMWs.

PMID- 16595024
TI  - Controversies in adjuvant endocrine treatment of premenopausal women.
AB  - For patients with hormone receptor-positive breast cancer, some form of endocrine
      therapy is central to the management of their disease. For premenopausal patients
      in whom estrogen synthesis occurs primarily in the ovaries, current treatment
      options include ovarian ablation or suppression and selective estrogen receptor
      modulators such as tamoxifen and toremifene. Ovarian ablation and tamoxifen have
      demonstrated their effectiveness in the adjuvant setting, reducing the risk of
      recurrence and death. However, although some studies suggest ovarian ablation
      results in an equivalent outcome to chemotherapy alone, studies examining the
      combination have not demonstrated a clear benefit with the addition of ovarian
      suppression to standard chemotherapy. Results from trials combining ovarian
      suppression with tamoxifen have also been inconclusive. Finally, although
      aromatase inhibitors cannot be used as monotherapy in premenopausal patients, the
      reduction in the risk of recurrence observed with the integration of these agents
      into adjuvant regimens in postmenopausal patients when compared with the standard
      5 years of tamoxifen has stimulated interest in evaluating the combination of
      ovarian suppression with an aromatase inhibitor in premenopausal women. Several
      ongoing trials will investigate these combinations as well as ovarian suppression
      plus tamoxifen.

PMID- 16595025
TI  - Exemestane as adjuvant treatment of early breast cancer: intergroup exemestane
      study/tamoxifen exemestane adjuvant multicenter trials.
AB  - This review summarizes the status of 2 major clinical trials involving
      exemestane, a nonsteroidal inactivator of aromatase. The first trial, Intergroup
      Exemestane Study (IES), has been previously reported. More than 4700
      postmenopausal women were randomized to receive exemestane versus continued
      tamoxifen at 2-3 years into 5 years of adjuvant tamoxifen. In the hormone
      receptor-positive group, there was a one-third improvement in disease-free
      survival and a near survival advantage (P = 0.08) for the crossover strategy. The
      second trial is the Tamoxifen Exemestane Adjuvant Multicenter (TEAM) study.
      Recently, the design was modified to take into account the information from the
      IES. In the initial phase of TEAM, 7000 patients were randomized to receive 5
      years of exemestane versus 5 years of tamoxifen. With the IES results, TEAM was
      modified so that 5 years of exemestane would be compared with 5 years of
      tamoxifen crossed over to exemestane. An additional 2500 patients have now been
      accrued. Updates of the IES and the first report of the TEAM might be available
      in 2006. The implications of these studies are discussed in this article.

PMID- 16595026
TI  - Emerging data on optimal adjuvant endocrine therapy: Breast International Group
      trial 1-98/MA.17.
AB  - In recent years, several major trials have studied aromatase inhibitors
      (AIs)/inactivators as adjuvant therapy for postmenopausal women with early-stage
      breast cancer. The AIs have demonstrated improved efficacy compared with 5 years
      of tamoxifen when used as initial therapy or when used sequentially after 2-3
      years. They also improve outcomes when used after 5 years of adjuvant tamoxifen
      in this patient population. In all cases, AIs improve disease-free survival
      compared with the standard 5 years of adjuvant tamoxifen, leading to a
      reassessment of the optimal adjuvant endocrine therapy for postmenopausal
      patients with breast cancer. The American Society of Clinical Oncology now
      recommends the inclusion of an AI into the adjuvant regimen at some point for
      most postmenopausal patients with hormone receptor-positive early-stage breast
      cancer. However, the optimal duration of AI therapy and the comparative efficacy
      and safety of the alternative strategies for their incorporation remain matters
      of debate. In addition, the long-term impact of AIs on other organs, such as the
      bone and cardiovascular systems, is not completely understood, and longer follow
      up of patients from these original trials as well as carefully planned future
      trials with appropriate substudies are essential to determine the optimal
      endocrine treatment strategy.

PMID- 16595027
TI  - Current status of combined hormone replacement therapy in clinical practice.
AB  - Approximately 20 million women worldwide use hormone replacement therapy (HRT).
      Formerly, it was thought to confer beneficial cardiac protection and reduce
      osteoporosis in addition to relieving the symptoms of menopause. However, many
      recent trials have contradicted these beliefs. The risk of breast cancer
      associated with HRT use has been well documented but underestimated. Many recent
      trials have reported higher than expected breast cancer incidence rates,
      particularly associated with combined HRT. Although it was believed estrogen
      conferred cardiac protection and reduced the incidence of myocardial ischemic
      events and cerebrovascular accidents, the more recent literature indicates that
      this is not true and that HRT users have a higher risk of cardiac and cerebral
      events. The role of HRT in clinical practice has been redefined. It is no longer
      an acceptable form of treatment for most women. The evidence indicates that the
      use of long-term HRT is no longer clinically justifiable.

PMID- 16595029
TI  - Assessing drug risks and benefits: lessons from postmenopausal hormone therapy
      studies.
AB  - The issue of safety standards for new drugs remains unsettled. Limitations of
      biomarker or observational studies for assessing global safety and efficacy of
      postmenopausal hormone therapy are highlighted by contrast with randomized
      clinical trial results. On the other hand, requiring large-scale, long-term
      outcome trials for every new drug might not be practical. Randomized trials with
      intermediate outcomes such as coronary angiography, coronary or carotid
      ultrasound, or coronary calcification present attractive alternatives. Trials
      with intermediate outcomes can be conducted with much smaller sample sizes and
      shorter duration, but the adequacy of these types of trials for assessment of
      safety and efficacy remains a topic of ongoing discussion in the scientific and
      regulatory communities.

PMID- 16595028
TI  - Coronary heart disease and stroke with aromatase inhibitor, tamoxifen, and
      menopausal hormone therapy use.
AB  - Results from the Women's Health Initiative randomized clinical trials of hormone
      therapy provide the clinical context for interpreting tamoxifen and aromatase
      inhibitor (AI) findings regarding coronary heart disease (CHD) and stroke. Of
      note is the potential link between increased stroke risk and increased dementia
      risk seen with the use of estrogen alone and the combination of
      estrogen/progestin. Like hormone therapy, tamoxifen has been found to generally
      lower low-density lipoprotein and total cholesterol but increase triglyceride
      levels. The preponderance of clinical evidence suggests that tamoxifen increases
      stroke risk and has no effect or modestly reduces CHD risk. Aromatase inhibitors
      generally do not influence low-density lipoprotein cholesterol and could modestly
      increase high-density lipoprotein cholesterol and reduce triglyceride levels.
      Current but limited evidence suggests that AIs have a modest increase or no
      effect on CHD as a class or as individual agents compared with tamoxifen. The
      influence of AIs on stroke is unsettled, and within-class differences might
      exist. In the adjuvant breast cancer setting, based on available evidence, the
      influence of AIs on CHD or stroke will infrequently influence overall patient
      outcome. If remaining issues are to be addressed, more rigorous CHD and stroke
      assessment procedures are needed in future trials evaluating AIs.

PMID- 16595032
TI  - Concomitant versus sequential chemotherapy in the treatment of early-stage and
      metastatic breast cancer.
AB  - Breast cancer is one of the most common malignancies in the Western world.
      Chemotherapy improves disease-free survival (DFS) and overall survival (OS) rates
      in women with early-stage breast cancer. Although anthracycline- and taxane-based
      regimens are considered most effective, the optimal way to administer them
      (sequentially vs. in combination) remains in question. In metastatic breast
      cancer, cytotoxic chemotherapy is the treatment of choice for patients with
      hormone receptor-negative tumors or rapidly progressive disease, regardless of
      hormone receptor status. The combination of chemotherapy and trastuzumab improves
      DFS and OS rates in patients with HER2-overexpressing metastatic breast cancer.
      In patients with HER2-negative tumors, the choice of single-agent sequential
      versus combination chemotherapy should be individualized. Sequential chemotherapy
      can produce OS rates similar to those of combination regimens and avoids the
      overlapping toxic effects of combination chemotherapy. However, response rates
      are generally higher and time to progression is longer with combination
      chemotherapy. At present, no predictive markers of response to chemotherapy are
      clinically useful in making treatment decisions for individual patients.
      Prospective studies are needed in order to validate the clinical utility of novel
      markers of response to specific chemotherapies and/or various schedules of
      administration.

PMID- 16595033
TI  - Phase II trial of weekly docetaxel/ gemcitabine as first-line chemotherapy in
      patients with locally recurrent or metastatic breast cancer.
AB  - PURPOSE: A phase II study evaluated weekly docetaxel/gemcitabine as first-line
      chemotherapy for locally recurrent or metastatic breast cancer in a multicenter
      community oncology practice setting. PATIENTS AND METHODS: Eligible patients who
      had not received chemotherapy for metastatic disease received docetaxel 30 mg/m2
      followed by gemcitabine 800 mg/m2, each administered weekly for 3 weeks (days 1,
      8, and 15), followed by a 1-week rest period (28-day cycle). Patients also
      received oral dexamethasone to reduce the incidence/severity of fluid retention
      and hypersensitivity reactions. Of the 46 enrolled patients, 45 were treated as
      part of the intent-to-treat (ITT) population and were evaluable for safety.
      RESULTS: There were 3 complete responses and 12 partial responses among the 39
      evaluable patients, for an objective response rate (ORR) of 39% (95% confidence
      interval [CI], 24%-54%). The ORR in the ITT population was 33% (95% CI, 18%-48%).
      Median time to response was 3.4 months, with a median response duration of 6.7
      months. Median survival was 15.8 months, and median time to progression was 5.8
      months. The most common grade 3/4 hematologic toxicity was neutropenia (13.3%);
      there was a low incidence of other grade 3/4 hematologic toxicities. Grade 3
      fatigue (15.6%) was the most common grade 3/4 nonhematologic toxicity, and grade
      2 alopecia occurred in 47% of patients. One patient who had been receiving
      chronic corticosteroid therapy died from treatment-related neutropenia and acute
      respiratory distress syndrome. CONCLUSION: These phase II results suggest that
      weekly docetaxel/gemcitabine is moderately active and well tolerated as first
      line therapy for locally recurrent or metastatic breast cancer. No clear
      advantage for combined weekly docetaxel/gemcitabine was observed compared with
      published results on the efficacy of docetaxel and gemcitabine given as single
      agents.

PMID- 16595034
TI  - Phase II study of neoadjuvant docetaxel/ vinorelbine followed by surgery and
      adjuvant doxorubicin/cyclophosphamide in women with stage II/III breast cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the combination of
      docetaxel plus vinorelbine as neoadjuvant chemotherapy for stage II/III locally
      advanced breast cancer. PATIENTS AND METHODS: Eligible women with stage IIA-IIIB
      or locoregional stage IV breast cancer were treated before surgery with 6 cycles
      of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2, repeated every 2 weeks with
      granulocyte colony-stimulating factor and quinolone prophylaxis. Pathologic
      complete response (pCR), viewed as an early surrogate for disease-free and
      overall survival, was the primary efficacy endpoint. Sixty patients were
      enrolled; 60% had T3 or T4 lesions, 67% had clinically palpable lymph nodes, and
      52% were hormone receptor positive. RESULTS: Fifty-nine patients were evaluable
      for pathologic response; 16 (27%) exhibited pCR in the breast alone (T0 Tis NX),
      20% exhibited a pCR in the breast and lymph nodes (T0 Tis N0), 24 (41%) had < 5
      mm of residual tumor, and 28 (47%) had node-negative disease at surgery. Relative
      dose intensity was 96% for docetaxel and 95% for vinorelbine. The clinical
      response rate was 98% (59 of 60 patients), including 38 complete responses (63%).
      Grade 3/4 neutropenia (95%), neutropenic fever (22%), mucositis (5%), and
      pulmonary toxicity (5%) occurred in >or= 5% of patients. Constipation was seen
      early but became insignificant after incorporating a prophylactic laxative
      regimen. Other toxicities have been minimal. CONCLUSION: With a clinical response
      rate of 98% and an in-breast pCR rate of 27%, docetaxel/vinorelbine is among the
      most active neoadjuvant regimens reported for locally advanced breast cancer.
      Docetaxel/vinorelbine can be administered in a dose-dense fashion while
      maintaining relative dose intensity. However, there was a significant incidence
      of fever and neutropenia despite the use of prophylactic growth factors and
      quinolones, indicating that lower doses of docetaxel/vinorelbine should be
      evaluated in future studies.

PMID- 16595035
TI  - Capecitabine/vinorelbine: an effective and well-tolerated regimen for women with
      pretreated advanced-stage breast cancer.
AB  - BACKGROUND: The combination of capecitabine and vinorelbine is a potentially
      valuable treatment regimen for patients with advanced-stage breast cancer. The
      drugs are easy to administer and do not cause significant alopecia. In order to
      identify the spectrum of toxicity of a regimen containing 2 drugs, we conducted
      an extended phase I study aimed at defining maximum tolerated doses, recommended
      doses, safety, and efficacy in patients with pretreated advanced-stage breast
      cancer. PATIENTS AND METHODS: Forty-nine patients with advanced-stage breast
      cancer were treated with escalating doses of oral capecitabine from 500 mg/m2 to
      1375 mg/m2 twice daily on days 1-14 and escalating doses of vinorelbine from 12.5
      mg/m2 to 25 mg/m2 intravenously (I.V.) on days 1 and 3 every 3 weeks. Almost all
      patients (90%) had received >or= 3 previous treatments for metastatic disease
      (anthracyclines, 76%; 5-flourouracil, 76%; taxanes, 29%). RESULTS: Dose level 9
      (capecitabine 1250 mg/m2 twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V.
      on days 1 and 3) was identified as the maximum tolerated dose. The most frequent
      clinical adverse events were nausea (78%), asthenia (59%), constipation (51%),
      mucositis (47%), and hand-foot syndrome (41%). The majority of events were mild
      to moderate; the only grade 4 clinical adverse events were diarrhea, fever, and
      thromboembolism, each of which occurred in 1 patient (2%) at dose level 8.
      Objective confirmed responses were observed in 18 patients (37%), including 1
      complete response (2%) and 17 partial responses (35%). Disease was stable in an
      additional 10 patients (20%), with a median duration of 6.3 months (range, 4-24
      months). CONCLUSION: The combination of the 2 drugs is very well tolerated and
      effective, especially considering the previous exposure to chemotherapy. The
      recommended dose for further phase II studies should be capecitabine 1250 mg/m2
      twice daily on days 1-14 and vinorelbine 22.5 mg/m2 I.V. on days 1 and 3.

PMID- 16595037
TI  - Repeat operative sentinel lymph node biopsy.
AB  - Because sentinel lymph node (SLN) biopsy continues to be used for staging in
      patients with breast cancer, physicians treating these patients will be faced
      with in-breast recurrences and new primary breast cancers in the treated breast.
      Repeat operative SLN biopsy might be feasible in this clinical scenario. This
      report describes the case of a patient with an ipsilateral different-site,
      recurrent, infiltrating ductal carcinoma 14 months after lumpectomy; negative SLN
      biopsy result; and radiation therapy, now with a positive SLN biopsy result.

PMID- 16595036
TI  - Plasma matrix metalloproteinases 7 and 9 in patients with metastatic breast
      cancer treated with marimastat or placebo: Eastern Cooperative Oncology Group
      trial E2196.
AB  - BACKGROUND: The purpose of this study was to evaluate the prognostic and
      predictive utility of measuring plasma levels of matrix metalloproteinase (MMP)-7
      and MMP-9 in patients with metastatic breast cancer (MBC) treated with the oral
      MMP inhibitor (MMPI) marimastat or a placebo. PATIENTS AND METHODS: We measured
      plasma levels of MMP-7 and MMP-9 using an enzyme-linked immunoassay method in 140
      evaluable patients with MBC enrolled on a multicenter clinical trial that
      compared the MMPI marimastat with placebo. Specimens were collected after
      completion of first-line chemotherapy in patients who had responding or stable
      disease and 3, 6, and 12 months after initiation of marimastat (10 mg orally
      twice daily) or placebo. RESULTS: Baseline plasma MMP-7 and MMP-9 levels did not
      correlate with each other or with progression-free or overall survival. In
      addition, serial evaluation of plasma MMP-7 and MMP-9 levels revealed no
      significant changes over time in the marimastat or placebo groups or any
      correlation with trough plasma marimastat level. CONCLUSION: We conclude that
      measurement of plasma MMP-7 or MMP-9 levels, as performed in our trial, was not a
      useful prognostic or predictive factor in patients with MBC or in patients
      treated with an MMPI.

PMID- 16595038
TI  - Docetaxel administered during pregnancy for inflammatory breast carcinoma.
AB  - We report the case of a 35-year-old pregnant woman with inflammatory breast
      carcinoma initially treated with 5-fluorouracil/doxorubicin/cyclophosphamide
      beginning her 13th week of pregnancy. There was no noticeable shrinkage of the
      axillary or breast tumors after 4 cycles, at which point the patient accepted a
      treatment change to docetaxel. Four cycles of docetaxel at 100 mg/m2 every 21
      days were delivered from the 25th week of pregnancy with good tolerance. She
      exhibited a clinical complete response, determined by clinical examination and
      imaging tests. Obstetric monitoring with fetal ultrasound showed normal fetal
      development throughout chemotherapy. After delivery of a healthy child, she
      underwent surgery, which showed tumor downstaging to pT0 N2, followed by
      radiation therapy and hormone therapy. This report suggests the safety of
      docetaxel after the first trimester of pregnancy.

PMID- 16595040
TI  - Persistent genital arousal in women -- a new syndrome entity.
AB  - The persistent sexual arousal syndrome (PSAS) is a newly described entity where
      women become involuntarily aroused genitally for extended periods in time in the
      absence of sexual desire. Genital vasoengorgement and oedema have been observed.
      These women are found to be usually very distressed. The cause of the syndrome in
      the majority of cases is unknown, although a number of women report symptoms
      after withdrawal from selective serotonin reuptake inhibitors (SSRI)
      antidepressants. There is no specific therapy at present, although
      electroconvulsive therapy (ECT) has resulted in clinical improvement in cases
      where there was concomitant severe depression.

PMID- 16595039
TI  - A phase II trial with trastuzumab and pertuzumab in patients with HER2
      overexpressed locally advanced and metastatic breast cancer.

PMID- 16595041
TI  - Facial atrophy in HIV-related fat redistribution syndrome: a plastic surgical
      perspective on treatment options and a look to the future.
AB  - Approximately 50% of patients on highly active antiretroviral therapy (HAART)
      develop lipodystrophy with central and visceral fat accumulation and/or facial
      and limb atrophy. Although the exact mechanisms of this are not fully understood,
      the facial atrophy encountered is secondary to atrophy of the subcutaneous fat,
      and not the deeper fat pads, as has been suggested. More recently, the above
      features in combination with hyperlipidaemia and insulin resistance have been
      described and are referred to as HIV-related fat redistribution syndrome. This
      review looks at treatment options available for this stigmatizing condition.

PMID- 16595042
TI  - Syphilis in pregnancy and the neonatal period.
AB  - The recent increase in the number of cases of syphilis in the UK, including among
      women of reproductive age, has stimulated the need for a review of practices
      concerning assessment and management of syphilis in pregnancy and the neonatal
      period. This paper summarizes available evidence from published guidelines,
      primary and secondary research. Optimal management of syphilis in pregnancy and
      the neonatal period relies on the early diagnosis and staging of maternal
      disease, prompt treatment to prevent congenital syphilis, and timely assessment
      of newborns.

PMID- 16595044
TI  - Survey of prioritizing/triaging of appointments in genitourinary medicine clinics
      in the UK: a British Co-operative Clinical Group survey.
AB  - A questionnaire was circulated to all lead genitourinary (GU) medicine physicians
      in the UK in November 2003 to obtain data on access, waiting times and triaging.
      Of the 143 responders, 92.3% departments had limited access to some or all GU
      medicine clinics. Where access was limited, 5.3% had no identifiable process in
      place to see urgent patients. The mean waiting times in clinics with an open
      appointment system only for a routine female and male appointment were 2.9 weeks
      and 2.8 weeks (range 2 days-10 weeks), respectively, and for an urgent
      appointment, two days (range same day-14 days), for both sexes. The survey has
      raised concerns that a number of departments did not consider as urgent for
      prioritizing, patients with documented untreated gonorrhoea, syphilis, or HIV, or
      contacts of patients with these conditions. This survey has highlighted a need
      for the national specialist society to provide guidance on prioritizing patients
      where access is limited.

PMID- 16595045
TI  - A rapid method for identifying high-risk patients consenting for HIV testing:
      introducing The Edinburgh Risk Assessment Table for HIV testing.
AB  - Lack of time for conducting standard HIV pre-test counselling has been reported
      as a barrier to HIV testing. Use of a risk assessment table will identify high
      risk patients to whom pre-test counselling may be limited. The aim of this study
      is to investigate the performance of a Risk Assessment Table for HIV testing
      designed in the Department of Genitourinary (GU) Medicine, Edinburgh. A
      prospective study was carried out on patients attending the Department of GU
      Medicine, Edinburgh between June 30th 2002 and July 1st 2003, who consented to
      HIV testing. Patients with any risk factor had standard pre-and post-test
      counselling. Those without any risk factor were tested and provided with leaflets
      on HIV testing.A total of 3337 patients were tested in the study period and 727
      (22%) had risk factor for HIV infection. Twenty-nine patients (0.9%) were HIV
      infected. The Risk Assessment Table failed to identify two infected patients.
      Routine use of the Risk Assessment Table saves time of the medical staff by only
      providing pre-test counselling to high-risk patients.

PMID- 16595047
TI  - Why do those using illicit drugs have higher rates of sexually transmitted
      infection?
AB  - The study was designed to assess the association between drug use and gonorrhoea
      in a UK setting and determine whether any differences identified could be
      explained by variations in sexual behaviour. A case control analysis was
      undertaken in a population of men and women presenting to an inner city sexually
      transmitted diseases clinic. The results were analysed using a multivariate model
      incorporating demographic and behavioural factors potentially associated with
      acquiring gonorrhoea. Infection with gonorrhoea was found to be associated with
      illicit drug use (odds ratio 1.8, 1.2-2.8) and the association became non
      significant after controlling for sexual behaviour factors. Moderate alcohol use
      (<5 units/week) was associated with acquiring gonorrhoea but heavier use was not.
      Patients who used illicit drugs had more casual partners and more foreign
      partners than those with no history of drug use, but an increased numbers of
      foreign partners were not associated with a higher prevalence of gonorrhoea. It
      was concluded that drug use is associated with gonorrhoea in a UK setting.
      Specific sexual behaviours reported by drug users may increase their risk of
      gonorrhoea and provide potential targets for behavioural interventions.

PMID- 16595046
TI  - Population-based enrolment of adolescents in a long-term follow-up trial of human
      papillomavirus vaccine efficacy.
AB  - We evaluated a study setting for assessment of the long-term vaccine efficacy
      (VE) of human papillomavirus (HPV) virus-like-particle (VLP) vaccine against
      cervical carcinoma. A total of 22,412 16- to 17-year old adolescent women from
      seven cities in Finland were invited by letter to participate in a phase III
      study of a quadrivalent HPV (types 6, 11, 16, 18) VLP vaccine, between September
      2002 and March 2003. A total of 30,947 18-year old women were invited to
      participate as unvaccinated controls. These women were asked about their
      willingness to participate in an HPV vaccination trial and to fill a health
      questionnaire. These three population-based cohorts of adolescent women,
      including women vaccinated with HPV vaccine or placebo vaccine and unvaccinated
      control women, are systematically followed over time. The study cohort database
      will be linked with the Finnish Cancer Registry using cervical carcinoma in situ
      (CIS) and invasive cervical carcinoma (ICC) as endpoints. Assuming that the
      cumulative incidence of CIS and ICC over 15 years is 0.45%, and that there is no
      loss to follow-up, and power of 80%, the determination of 70% total VE will
      require 3357 HPV vaccine recipients, 3357 placebo vaccine recipients, and 6714
      unvaccinated controls. At the baseline, 2632 (12%) of the invited adolescents
      volunteered to the phase III vaccination trial, and 6790 (22%) responded to the
      questionnaire study. During a recruitment period of 10 months, 874 HPV vaccine
      recipients, 875 placebo recipients and 1919 unvaccinated controls were enrolled.
      Population-based enrollment of large cohorts of vaccinated and unvaccinated
      adolescents for passive registry-based follow-up with cervical carcinoma as the
      end-point is feasible and currently going on in Finland.

PMID- 16595048
TI  - Dramatic increase in a single genotype of TRNG ciprofloxacin-resistant Neisseria
      gonorrhoeae isolates in men who have sex with men.
AB  - In 2003, episodes of gonorrhoea caused by ciprofloxacin-resistant strains
      increased to 15.3% from 11% in 2002. This was coincident with a marked increase
      in strains characterized as serogroup WI, ciprofloxacin-resistant bearing the
      tetracycline resistance plasmid. Molecular typing of these strains, using
      Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) revealed 71% (34/48)
      were of the same sequence type, ST338, accounting for 4.1% (34/824) of all
      strains in 2003. Epidemiological data demonstrated that transmission of ST338 was
      associated with men who have sex with men (MSM; 23/27), acquisition within the UK
      (22/26) and having two or more partners in the previous three-month period
      (18/27). The combined use of highly discriminatory typing and epidemiological
      surveillance helps to identify successful transmission networks.

PMID- 16595049
TI  - Cohort analysis of two multidisciplined adherence intervention programmes for
      patients on antiretroviral therapy.
AB  - The aim was to analyse data from two randomized controlled trials (RCTs) to
      determine if an adherence intervention programme for antiretroviral therapy (ART)
      resulted in a reduction in viral load. A cohort analysis of pre- and post
      intervention viral loads and CD4 counts using paired analysis was undertaken on
      participants who received the intervention programme. Analysis was also
      undertaken on a control group. The intervention participants had an increase in
      mean CD4 count (450-478, P = 0.26), and a decline in log viral load (2.48-2.36, P
      = 0.056). The control group had a decline in mean CD4 counts (596-570, P = 0.53),
      and an increase in log viral load (2.09-2.11, P = 0.78). The use of an adherence
      intervention programme is associated with a decrease in mean viral load, which is
      in contrast to the control group that demonstrated an increase in viral load over
      time.

PMID- 16595050
TI  - Vaginal colonization with Candida spp. in human immunodeficiency virus-infected
      women: a cohort study.
AB  - We have conducted a longitudinal study on factors associated with candidal
      vaginal colonization, a precursor of vaginitis, in a cohort of HIV-infected women
      in Italy. All consecutive women attending a single, tertiary care clinical site
      were offered free screening for sexually transmitted infections and genital
      disorders every 6-12 months. Candidal vaginal colonization was defined as a
      positive culture for Candida spp. in an asymptomatic woman. From January 1998 to
      July 2002 we analysed 214 women. The baseline prevalence of candidal vaginal
      colonization was 16.8%. In the logistic regression analysis, the time since HIV
      infection > or =36 months (odds ratio [OR] = 0.18, 95% confidence interval [CI]
      0.016-0.53, P = 0.002) and a plasma viral load > or =10,000 copies/mL (OR = 3.9,
      95% CI 1.03-14.9, P = 0.045) were independently associated with candidal
      colonization. Among 130 women who were followed for a mean period of 24 months,
      the incidence of vaginal colonization was 10.7/100 women-years. In the Cox
      regression analysis, a CD4(+) T-lymphocytes count <100 cells/microL during the
      follow-up was associated with an increased risk of candidal vaginal colonization
      (OR = 4.45, C.I. = 1.20-16.81, P = 0.03). Risk of candidal vaginal colonization
      episodes in HIV-infected women significantly increase when CD4(+) T-lymphocytes
      are less than 100.

PMID- 16595051
TI  - Interpersonal and social network influences on gay men's communication about
      unprotected sex.
AB  - This study documents gay men's communication patterns about unprotected sex. Gay
      men (n = 206) completed a structured interview about their social networks. The
      167 men who had had unprotected sex identified 1390 social relations; 32.6% had
      involved discussing an episode of unprotected sex. Discussions about unprotected
      sex were associated with the nature of the relationship, whether the other party
      was gay or lesbian, how often the parties spent time together, whether the
      relationship had been sexual, and the density of the other parties' social
      network. Social networks provide an important context for the maintenance of safe
      sex cultures.

PMID- 16595052
TI  - An algorithmic approach to intracranial mass lesions in HIV/AIDS.
AB  - We developed a diagnostic and therapeutic algorithm for intracranial mass lesions
      in patients with HIV/AIDS that obviates the need for neurosurgical intervention.
      The approach is based upon CD4(+) lymphocyte count, serum toxoplasma
      immunoglobulin G (IgG) serology, chest X-ray, routine lumbar puncture studies,
      cerebrospinal fluid (CSF) cytology, CSF adenosine deaminase or Mycobacterium
      tuberculosis polymerase chain reaction testing, single positron emission-computed
      tomography (SPECT) scanning for intracranial enhancing lesions, and limited
      therapeutic trials. Over a 12-month period involving 26 patients, we found that
      the algorithm correctly identified the aetiology of focal intracranial lesions in
      all 23 evaluable patients. Costs for SPECT scanning for the entire study cohort
      were more than offset by the savings achieved by reduced hospital stays for the
      four patients with lymphoma alone. An algorithmic approach can accurately
      identify the cause(s) of central nervous system (CNS) mass lesions in HIV
      infected patients, and SPECT scanning can replace stereotactic brain biopsy in
      most cases where opportunistic malignancy is suspected.

PMID- 16595053
TI  - Rectal gonorrhoea in men -- is microscopy still a useful tool?
AB  - Rectal gonorrhoea (GC) in men may cause anal discharge or proctitis, but these
      symptoms have been shown to correlate poorly with rectal infection. Culture of
      Neisseria gonorrhoeae from an exposed site offers a readily available, sensitive
      and cheap diagnostic test, and is currently the gold standard for diagnosis;
      however, these results can take a few days and therefore do not offer an instant
      diagnosis. Gram staining of rectal smears for N. gonorrhoeae has a low
      sensitivity but a high specificity when performed by experienced personnel. We
      audited whether rectal microscopy increased the number of patients diagnosed and
      treated for rectal GC at initial presentation at one inner London genitourinary
      clinic over a 12-month period. One hundred and thirty-six episodes of rectal GC
      were identified in 132 men. In all, 134/136 had rectal microscopy of whom, 47/134
      (35%) were smear-positive for GC. Of the 136 cases, 90 received antibiotics for
      GC at their first presentation. Twenty-four of 90 (27%) would not have been
      treated until culture results were available, if rectal microscopy had not been
      performed. These results suggest that rectal microscopy remains an important tool
      and increases the proportion of men treated for GC at their first attendance.

PMID- 16595054
TI  - Lactobacillus acidophilus bacteraemia after use of a probiotic in a patient with
      AIDS and Hodgkin's disease.
AB  - We report the case of a patient who developed bacteraemia and septic pulmonary
      emboli with Lactobacillus acidophilus after taking a probiotic containing this
      organism.

PMID- 16595055
TI  - The future of the sexual health services between the economic rhetoric and
      principles of communicable diseases control.

PMID- 16595056
TI  - One-year experience of APTIMA COMBO 2 Transcription Mediated Assay (TMA) for
      chlamydia and gonorrhoea in a district general hospital.

PMID- 16595057
TI  - Singularities affect dynamics of learning in neuromanifolds.
AB  - The parameter spaces of hierarchical systems such as multilayer perceptrons
      include singularities due to the symmetry and degeneration of hidden units. A
      parameter space forms a geometrical manifold, called the neuromanifold in the
      case of neural networks. Such a model is identified with a statistical model, and
      a Riemannian metric is given by the Fisher information matrix. However, the
      matrix degenerates at singularities. Such a singular structure is ubiquitous not
      only in multilayer perceptrons but also in the gaussian mixture probability
      densities, ARMA time-series model, and many other cases. The standard statistical
      paradigm of the Cramer-Rao theorem does not hold, and the singularity gives rise
      to strange behaviors in parameter estimation, hypothesis testing, Bayesian
      inference, model selection, and in particular, the dynamics of learning from
      examples. Prevailing theories so far have not paid much attention to the problem
      caused by singularity, relying only on ordinary statistical theories developed
      for regular (nonsingular) models. Only recently have researchers remarked on the
      effects of singularity, and theories are now being developed. This article gives
      an overview of the phenomena caused by the singularities of statistical manifolds
      related to multilayer perceptrons and gaussian mixtures. We demonstrate our
      recent results on these problems. Simple toy models are also used to show
      explicit solutions. We explain that the maximum likelihood estimator is no longer
      subject to the gaussian distribution even asymptotically, because the Fisher
      information matrix degenerates, that the model selection criteria such as AIC,
      BIC, and MDL fail to hold in these models, that a smooth Bayesian prior becomes
      singular in such models, and that the trajectories of dynamics of learning are
      strongly affected by the singularity, causing plateaus or slow manifolds in the
      parameter space. The natural gradient method is shown to perform well because it
      takes the singular geometrical structure into account. The generalization error
      and the training error are studied in some examples.

PMID- 16595058
TI  - How noise affects the synchronization properties of recurrent networks of
      inhibitory neurons.
AB  - GABAergic interneurons play a major role in the emergence of various types of
      synchronous oscillatory patterns of activity in the central nervous system.
      Motivated by these experimental facts, modeling studies have investigated
      mechanisms for the emergence of coherent activity in networks of inhibitory
      neurons. However, most of these studies have focused either when the noise in the
      network is absent or weak or in the opposite situation when it is strong. Hence,
      a full picture of how noise affects the dynamics of such systems is still
      lacking. The aim of this letter is to provide a more comprehensive understanding
      of the mechanisms by which the asynchronous states in large, fully connected
      networks of inhibitory neurons are destabilized as a function of the noise level.
      Three types of single neuron models are considered: the leaky integrate-and-fire
      (LIF) model, the exponential integrate-and-fire (EIF), model and conductance
      based models involving sodium and potassium Hodgkin-Huxley (HH) currents. We show
      that in all models, the instabilities of the asynchronous state can be classified
      in two classes. The first one consists of clustering instabilities, which exist
      in a restricted range of noise. These instabilities lead to synchronous patterns
      in which the population of neurons is broken into clusters of synchronously
      firing neurons. The irregularity of the firing patterns of the neurons is weak.
      The second class of instabilities, termed oscillatory firing rate instabilities,
      exists at any value of noise. They lead to cluster state at low noise. As the
      noise is increased, the instability occurs at larger coupling, and the pattern of
      firing that emerges becomes more irregular. In the regime of high noise and
      strong coupling, these instabilities lead to stochastic oscillations in which
      neurons fire in an approximately Poisson way with a common instantaneous
      probability of firing that oscillates in time.

PMID- 16595059
TI  - Analysis of synchronization between two modules of pulse neural networks with
      excitatory and inhibitory connections.
AB  - To study the synchronized oscillations among distant neurons in the visual
      cortex, we analyzed the synchronization between two modules of pulse neural
      networks using the phase response function. It was found that the intermodule
      connections from excitatory to excitatory ensembles tend to stabilize the
      antiphase synchronization and that the intermodule connections from excitatory to
      inhibitory ensembles tend to stabilize the in-phase synchronization. It was also
      found that the intermodule synchronization was more noticeable when the inner
      module synchronization was weak.

PMID- 16595060
TI  - A sensorimotor map: modulating lateral interactions for anticipation and
      planning.
AB  - Experimental studies of reasoning and planned behavior have provided evidence
      that nervous systems use internal models to perform predictive motor control,
      imagery, inference, and planning. Classical (model-free) reinforcement learning
      approaches omit such a model; standard sensorimotor models account for forward
      and backward functions of sensorimotor dependencies but do not provide a proper
      neural representation on which to realize planning. We propose a sensorimotor map
      to represent such an internal model. The map learns a state representation
      similar to self-organizing maps but is inherently coupled to sensor and motor
      signals. Motor activations modulate the lateral connection strengths and thereby
      induce anticipatory shifts of the activity peak on the sensorimotor map. This
      mechanism encodes a model of the change of stimuli depending on the current motor
      activities. The activation dynamics on the map are derived from neural field
      models. An additional dynamic process on the sensorimotor map (derived from
      dynamic programming) realizes planning and emits corresponding goal-directed
      motor sequences, for instance, to navigate through a maze.

PMID- 16595061
TI  - A reflexive neural network for dynamic biped walking control.
AB  - Biped walking remains a difficult problem, and robot models can greatly
      facilitate our understanding of the underlying biomechanical principles as well
      as their neuronal control. The goal of this study is to specifically demonstrate
      that stable biped walking can be achieved by combining the physical properties of
      the walking robot with a small, reflex-based neuronal network governed mainly by
      local sensor signals. Building on earlier work (Taga, 1995; Cruse, Kindermann,
      Schumm, Dean, & Schmitz, 1998), this study shows that human-like gaits emerge
      without specific position or trajectory control and that the walker is able to
      compensate small disturbances through its own dynamical properties. The reflexive
      controller used here has the following characteristics, which are different from
      earlier approaches: (1) Control is mainly local. Hence, it uses only two signals
      (anterior extreme angle and ground contact), which operate at the interjoint
      level. All other signals operate only at single joints. (2) Neither position
      control nor trajectory tracking control is used. Instead, the approximate nature
      of the local reflexes on each joint allows the robot mechanics itself (e.g., its
      passive dynamics) to contribute substantially to the overall gait trajectory
      computation. (3) The motor control scheme used in the local reflexes of our robot
      is more straightforward and has more biological plausibility than that of other
      robots, because the outputs of the motor neurons in our reflexive controller are
      directly driving the motors of the joints rather than working as references for
      position or velocity control. As a consequence, the neural controller and the
      robot mechanics are closely coupled as a neuromechanical system, and this study
      emphasizes that dynamically stable biped walking gaits emerge from the coupling
      between neural computation and physical computation. This is demonstrated by
      different walking experiments using a real robot as well as by a Poincare map
      analysis applied on a model of the robot in order to assess its stability.

PMID- 16595063
TI  - Payoff-monotonic game dynamics and the maximum clique problem.
AB  - Evolutionary game-theoretic models and, in particular, the so-called replicator
      equations have recently proven to be remarkably effective at approximately
      solving the maximum clique and related problems. The approach is centered around
      a classic result from graph theory that formulates the maximum clique problem as
      a standard (continuous) quadratic program and exploits the dynamical properties
      of these models, which, under a certain symmetry assumption, possess a Lyapunov
      function. In this letter, we generalize previous work along these lines in
      several respects. We introduce a wide family of game-dynamic equations known as
      payoff-monotonic dynamics, of which replicator dynamics are a special instance,
      and show that they enjoy precisely the same dynamical properties as standard
      replicator equations. These properties make any member of this family a potential
      heuristic for solving standard quadratic programs and, in particular, the maximum
      clique problem. Extensive simulations, performed on random as well as DIMACS
      benchmark graphs, show that this class contains dynamics that are considerably
      faster than and at least as accurate as replicator equations. One problem
      associated with these models, however, relates to their inability to escape from
      poor local solutions. To overcome this drawback, we focus on a particular
      subclass of payoff-monotonic dynamics used to model the evolution of behavior via
      imitation processes and study the stability of their equilibria when a
      regularization parameter is allowed to take on negative values. A detailed
      analysis of these properties suggests a whole class of annealed imitation
      heuristics for the maximum clique problem, which are based on the idea of varying
      the parameter during the imitation optimization process in a principled way, so
      as to avoid unwanted inefficient solutions. Experiments show that the proposed
      annealing procedure does help to avoid poor local optima by initially driving the
      dynamics toward promising regions in state space. Furthermore, the models
      outperform state-of-the-art neural network algorithms for maximum clique, such as
      mean field annealing, and compare well with powerful continuous-based heuristics.

PMID- 16595062
TI  - A set probability technique for detecting relative time order across multiple
      neurons.
AB  - With the development of multielectrode recording techniques, it is possible to
      measure the cell firing patterns of multiple neurons simultaneously, generating a
      large quantity of data. Identification of the firing patterns within these large
      groups of cells is an important and a challenging problem in data analysis. Here,
      we consider the problem of measuring the significance of a repeat in the cell
      firing sequence across arbitrary numbers of cells. In particular, we consider the
      question, given a ranked order of cells numbered 1 to N, what is the probability
      that another sequence of length n contains j consecutive increasing elements?
      Assuming each element of the sequence is drawn with replacement from the numbers
      1 through N, we derive a recursive formula for the probability of the sequence of
      length j or more. For n<2j, a closed-form solution is derived. For n>or=2j, we
      obtain upper and lower bounds for these probabilities for various combinations of
      parameter values. These can be computed very quickly. For a typical case with
      small N (<10) and large n (<3000), sequences of 7 and 8 are statistically very
      unlikely. A potential application of this technique is in the detection of
      repeats in hippocampal place cell order during sleep. Unlike most previous
      articles on increasing runs in random lists, we use a probability approach based
      on sets of overlapping sequences.

PMID- 16595064
TI  - Phase I study of docetaxel and topotecan in patients with advanced malignancies.
AB  - BACKGROUND: Docetaxel and topotecan are drugs with different mechanisms of action
      and significant activity against various tumour types. Topotecan may influence
      docetaxel metabolism by inhibiting the CYP3A4 enzyme. We designed a phase I study
      to evaluate the maximum tolerated dose of this combination and to assess the
      impact of pharmacokinetic interactions of the two drugs on toxicity. METHODS:
      Docetaxel and topotecan were administered intravenously on day 1, and days 1 - 5
      respectively, using a phase I dose escalation design. Plasma samples were
      analysed to determine docetaxel and topotecan concentration by HPLC with
      subsequent pharmacokinetic analysis using NONMEM. RESULTS: Of the 17 patients
      enrolled in the trial, 11 had grade 3 and 4 neutropenia and 1 had grade 4
      thrombocytopenia. Nonhaematological toxicities were less frequent. The maximum
      tolerated dose for docetaxel and topotecan were 60 mg/m(2) on day 1 and 0.75
      mg/m(2) days 1 - 5, respectively. One patient had stable disease. Subjects with
      grade >or= 3 haematologic toxicity had higher plasma docetaxel or topotecan area
      under the curve (AUC) (docetaxel 1.03 +/- 0.11 mg-hr/L versus 0.73 +/- 0.13 mg
      hr/L; topotecan 65.8 +/- 14.6 mcg-hr/L versus 41.6 +/- 13.9 mcg-hr/L). There was
      no additive effect of the AUC of the two drugs on the likelihood of grade >or= 3
      haematologic toxicity by multiple logistic regression. CONCLUSION: The dose
      limiting toxicity seen with the combination of docetaxel and topotecan was
      myelosuppression. Future trials will require growth factor support if this
      combination is pursued.

PMID- 16595065
TI  - Survey of topical oral solutions for the treatment of chemo-induced oral
      mucositis.
AB  - PURPOSE: The objectives of this study were (1) to describe the usage of topical
      oral solutions in patients experiencing chemotherapy-induced oral mucositis
      (CIOM); and (2) to survey the care of oral mucositis provided to patients by
      clinical oncology pharmacists in institutional settings. METHODS: Surveys were
      distributed to institutional pharmacists in the US, who were asked to provide the
      components of their 'magic mouthwash'. Other questions included whether an
      institutional mucositis management guideline is available and what is the
      involvement of clinical pharmacy in mucositis care. RESULTS: Forty institutions
      returned surveys during the study period. The top five ingredients used to
      compound the magic mouthwash are diphenhydramine, viscous lidocaine, magnesium
      hydroxide/aluminum hydroxide, nystatin and corticosteroids. Most institutions
      administer the mouthwash every 4 hours (36%) or every 6 hours (36%). Of the
      surveyed institutions, 33% currently possess guidelines for the management of
      CIOM. CONCLUSIONS: Most institutions in the country formulate their topical
      solution, or magic mouthwash, with a variety of ingredients. There is a need to
      standardize the ingredients used to compound the magic mouthwash, in order to
      fully evaluate the efficacy of the solution to manage CIOM.

PMID- 16595066
TI  - Erythropoietin and neuroprotection: a therapeutic perspective.
AB  - Recombinant erythropoietin (EPO) is used to correct for anaemia caused by chronic
      renal failure or cancer therapy. Improvement of the quality of life of anaemic
      patients treated with EPO was recently demonstrated and preliminary clinical
      results suggest an improvement of cognitive functions in patients receiving EPO.
      High expression of EPO and its receptor in the brain during embryonic development
      has led to the investigation of not only the neurotrophic role of EPO but also
      its neuroprotective properties. The neuroprotective effects of EPO have various
      complementary actions including antagonism of the effects of glutamate, increased
      expression of antioxidant enzymes, changes in production of neurotransmitters and
      induction of neuroglobin. Convincing experimental results suggest a blood-brain
      transport of EPO whereas clinical pharmacokinetic data do not as yet support
      this. The neuroprotective effects of EPO and its therapeutic promise need to be
      underlined.

PMID- 16595067
TI  - Actinic keratosis and capecitabine therapy.
AB  - Topical application of 5-fluorouracil (5-FU) is one of the most effective
      clinical strategies available to treat actinic keratosis (AK). During treatment,
      an apparent toxic skin reaction occurs before dermal quiescence ensues. We report
      a case of a typical flare of AK in a woman treated with capecitabine for advanced
      breast cancer.

PMID- 16595068
TI  - Leaching of diethylhexyl phthalate from polyvinyl chloride materials into
      etoposide intravenous solutions.
AB  - Etoposide intravenous solution is associated with leaching of diethylhexyl
      phthalate (DEHP) from bags and tubings made from polyvinyl chloride (PVC). Recent
      evidence suggests that this may be more substantial than previously found. Since
      DEHP is potentially hepatotoxic and carcinogenic, it is preferable to prepare and
      administer etoposide bags and tubings made from non-PVC materials.

PMID- 16595069
TI  - Management of extravasation of oxaliplatin.
AB  - Oxaliplatin extravasation has been associated with local pain and inflammation
      which may be severe and lead to complications including necrosis. Recent case
      reports suggest that oxaliplatin may be better classified as an irritant when
      extravasated. The optimal management of oxaliplatin extravasation however remains
      uncertain. Cold compress may cause local vasoconstriction and reduce cellular
      injury. However, it may potentially precipitate or worsen peripheral neuropathy.
      Warm compress may increase drug removal by local vasodilation and avoid
      peripheral neuropathy. However, it may potentially increase cellular uptake and
      hence injury. Further research into this area is needed.

PMID- 16595071
TI  - Human mutation databases.

PMID- 16595072
TI  - Human SNPs resulting in premature stop codons and protein truncation.
AB  - Single nucleotide polymorphisms (SNPs) constitute the most common type of genetic
      variation in humans. SNPs introducing premature termination codons (PTCs), herein
      called X-SNPs, can alter the stability and function of transcripts and proteins
      and thus are considered to be biologically important. Initial studies suggested a
      strong selection against such variations/mutations. In this study, we undertook a
      genome-wide systematic screening to identify human X-SNPs using the dbSNP
      database. Our results demonstrated the presence of 28 X-SNPs from 28 genes with
      known minor allele frequencies. Eight X-SNPs (28.6 per cent) were predicted to
      cause transcript degradation by nonsense-mediated mRNA decay. Seventeen X-SNPs
      (60.7 per cent) resulted in moderate to severe truncation at the C-terminus of
      the proteins (deletion of >50 per cent of the amino acids). The majority of the X
      SNPs (78.6 per cent) represent commonly occurring SNPs, by contrast with the
      rarely occurring disease-causing PTC mutations. Interestingly, X-SNPs displayed a
      non-uniform distribution across human populations: eight X-SNPs were reported to
      be prevalent across three different human populations, whereas six X-SNPs were
      found exclusively in one or two population(s). In conclusion, we have
      systematically investigated human SNPs introducing PTCs with respect to their
      possible biological consequences, distributions across different human
      populations and evolutionary aspects. We believe that the SNPs reported here are
      likely to affect gene/protein function, although their biological and
      evolutionary roles need to be further investigated.

PMID- 16595073
TI  - Functional nsSNPs from carcinogenesis-related genes expressed in breast tissue:
      potential breast cancer risk alleles and their distribution across human
      populations.
AB  - Although highly penetrant alleles of BRCA1 and BRCA2 have been shown to
      predispose to breast cancer, the majority of breast cancer cases are assumed to
      result from the presence of low-moderate penetrant alleles and environmental
      carcinogens. Non-synonymous single nucleotide polymorphisms (nsSNPs) are
      hypothesised to contribute to disease susceptibility and approximately 30 per
      cent of them are predicted to have a biological significance. In this study, we
      have applied a bioinformatics-based strategy to identify breast cancer-related
      nsSNPs from 981 carcinogenesis-related genes expressed in breast tissue. Our
      results revealed a total of 367 validated nsSNPs, 109 (29.7 per cent) of which
      are predicted to affect the protein function (functional nsSNPs), suggesting that
      these nsSNPs are likely to influence the development and homeostasis of breast
      tissue and hence contribute to breast cancer susceptibility. Sixty-seven of the
      functional nsSNPs presented as commonly occurring nsSNPs (minor allele
      frequencies > or =5 per cent), representing excellent candidates for breast
      cancer susceptibility. Additionally, a non-uniform distribution of the common
      functional nsSNPs among different human populations was observed: 15 nsSNPs were
      reported to be present in all populations analysed, whereas another set of 15
      nsSNPs was specific to particular population(s). We propose that the nsSNPs
      analysed in this study constitute a unique resource of potential genetic factors
      for breast cancer susceptibility. Furthermore, the variations in functional nsSNP
      allele frequencies across major population backgrounds may point to the potential
      variability of the molecular basis of breast cancer predisposition and treatment
      response among different human populations.

PMID- 16595074
TI  - Fabry disease: identification of 50 novel alpha-galactosidase A mutations causing
      the classic phenotype and three-dimensional structural analysis of 29 missense
      mutations.
AB  - Fabry disease, an X-linked recessive inborn error of glycosphingolipid
      catabolism, results from the deficient activity of the lysosomal
      exoglycohydrolase, alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A). The
      molecular lesions in the alpha-Gal A gene causing the classic phenotype of Fabry
      disease in 66 unrelated families were determined. In 49 families, 50 new
      mutations were identified, including: 29 missense mutations (N34K, T41I, D93V,
      R112S, L166G, G171D, M187T, S201Y, S201F, D234E, W236R, D264Y, M267R, V269M,
      G271S, G271V, S276G, Q283P, A285P, A285D, M290I, P293T, Q312H, Q321R, G328V,
      E338K, A348P, E358A, Q386P); nine nonsense mutations (C56X, E79X, K127X, Y151X,
      Y173X, L177X, W262X, Q306X, E338X); five splicing defects (IVS4-1G>A, IVS5-2A>G,
      IVS5+3A>G, IVS5+4A>G, IVS6-1G>C); four small deletions (18delA, 457delGAC,
      567delG, 1096delACCAT); one small insertion (996insC); one 3.1 kilobase Alu-Alu
      deletion (which included exon 2); and one complex mutation (K374R, 1124delGAG).
      In 18 families, 17 previously reported mutations were identified, with R112C
      occurring in two families. In two classically affected families, affected males
      were identified with two mutations: one with two novel mutations, D264Y and V269M
      and the other with one novel (Q312H) and one previously reported (A143T)
      mutation. Transient expression of the individual mutations revealed that D264Y
      and Q312H were localised in the endoplasmic reticulum and had no detectable or
      markedly reduced activity, whereas V269M and A143T were localised in lysosomes
      and had approximately 10 per cent and approximately 35 per cent of expressed wild
      type activity, respectively. Structural analyses based on the enzyme's three
      dimensional structure predicted the effect of the 29 novel missense mutations on
      the mutant glycoprotein's structure. Of note, three novel mutations
      (approximately 10 per cent) were predicted not to significantly alter the
      glycoprotein's structure; however, they were disease causing. These studies
      further define the molecular heterogeneity of the alpha-Gal A mutations in
      classical Fabry disease, permit precise heterozygote detection and prenatal
      diagnosis, and provide insights into the structural alterations of the mutant
      enzymes that cause the classic phenotype.

PMID- 16595076
TI  - Multifactor dimensionality reduction: an analysis strategy for modelling and
      detecting gene-gene interactions in human genetics and pharmacogenomics studies.
AB  - The detection of gene-gene and gene-environment interactions associated with
      complex human disease or pharmacogenomic endpoints is a difficult challenge for
      human geneticists. Unlike rare, Mendelian diseases that are associated with a
      single gene, most common diseases are caused by the non-linear interaction of
      numerous genetic and environmental variables. The dimensionality involved in the
      evaluation of combinations of many such variables quickly diminishes the
      usefulness of traditional, parametric statistical methods. Multifactor
      dimensionality reduction (MDR) is a novel and powerful statistical tool for
      detecting and modelling epistasis. MDR is a non-parametric and model-free
      approach that has been shown to have reasonable power to detect epistasis in both
      theoretical and empirical studies. MDR has detected interactions in diseases such
      as sporadic breast cancer, multiple sclerosis and essential hypertension. As this
      method is more frequently applied, and was gained acceptance in the study of
      human disease and pharmacogenomics, it is becoming increasingly important that
      the implementation of the MDR approach is properly understood. As with all
      statistical methods, MDR is only powerful and useful when implemented correctly.
      Concerns regarding dataset structure, configuration parameters and the proper
      execution of permutation testing in reference to a particular dataset and
      configuration are essential to the method's effectiveness. The detection,
      characterisation and interpretation of gene-gene and gene-environment
      interactions are expected to improve the diagnosis, prevention and treatment of
      common human diseases. MDR can be a powerful tool in reaching these goals when
      used appropriately.

PMID- 16595075
TI  - Detecting multiple associations in genome-wide studies.
AB  - Recent developments in the statistical analysis of genome-wide studies are
      reviewed. Genome-wide analyses are becoming increasingly common in areas such as
      scans for disease-associated markers and gene expression profiling. The data
      generated by these studies present new problems for statistical analysis, owing
      to the large number of hypothesis tests, comparatively small sample size and
      modest number of true gene effects. In this review, strategies are described for
      optimising the genotyping cost by discarding promising genes at an earlier stage,
      saving resources for the genes that show a trend of association. In addition,
      there is a review of new methods of analysis that combine evidence across genes
      to increase sensitivity to multiple true associations in the presence of many non
      associated genes. Some methods achieve this by including only the most
      significant results, whereas others model the overall distribution of results as
      a mixture of distributions from true and null effects. Because genes are
      correlated even when having no effect, permutation testing is often necessary to
      estimate the overall significance, but this can be very time consuming.
      Efficiency can be improved by fitting a parametric distribution to permutation
      replicates, which can be re-used in subsequent analyses. Methods are also
      available to generate random draws from the permutation distribution. The review
      also includes discussion of new error measures that give a more reasonable
      interpretation of genome-wide studies, together with improved sensitivity. The
      false discovery rate allows a controlled proportion of positive results to be
      false, while detecting more true positives; and the local false discovery rate
      and false-positive report probability give clarity on whether or not a
      statistically significant test represents a real discovery.

PMID- 16595077
TI  - Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family.
AB  - The NAD(P)H:quinone acceptor oxidoreductase (NQO) gene family belongs to the
      flavoprotein clan and, in the human genome, consists of two genes (NQO1 and
      NQO2). These two genes encode cytosolic flavoenzymes that catalyse the beneficial
      two-electron reduction of quinones to hydroquinones. This reaction prevents the
      unwanted one-electron reduction of quinones by other quinone reductases; one
      electron reduction results in the formation of reactive oxygen species, generated
      by redox cycling of semiquinones in the presence of molecular oxygen. Both the
      mammalian NQO1 and NQO2 genes are upregulated as a part of the oxidative stress
      response and are inexplicably overexpressed in particular types of tumours. A non
      synonymous mutation in the NQO1 gene, leading to absence of enzyme activity, has
      been associated with an increased risk of myeloid leukaemia and other types of
      blood dyscrasia in workers exposed to benzene. NQO2 has a melatonin-binding site,
      which may explain the anti-oxidant role of melatonin. An ancient NQO3 subfamily
      exists in eubacteria and the authors suggest that there should be additional
      divisions of the NQO family to include the NQO4 subfamily in fungi and NQO5
      subfamily in archaebacteria. Interestingly, no NQO genes could be identified in
      the worm, fly, sea squirt or plants; because these taxa carry quinone reductases
      capable of one- and two-electron reductions, there has been either convergent
      evolution or redundancy to account for the appearance of these enzyme functions
      whenever they have been needed during evolution.

PMID- 16595078
TI  - A survey of data mining methods for linkage disequilibrium mapping.
AB  - Data mining methods are gaining more interest as potential tools in mapping and
      identification of complex disease loci. The methods are well suited to large
      numbers of genetic marker loci produced by high-throughput laboratory analyses,
      but also might be useful for clarifying the phenotype definitions prior to more
      traditional mapping analyses. Here, the current data mining-based methods for
      linkage disequilibrium mapping and phenotype analyses are reviewed.

PMID- 16595079
TI  - Evaluation of molecular techniques in prediction and diagnosis of cytomegalovirus
      disease in immunocompromised patients.
AB  - OBJECTIVES: To evaluate selected molecular tests in diagnosis and screening of
      cytomegalovirus (CMV) infection in immunosuppressed patients. DESIGN: Clinical
      and cost-effectiveness were assessed through a prospective two-stage trial of CMV
      screening regimes in a routine service setting. Different molecular test results
      were fed back to clinicians in each stage, plus antigenaemia results. The
      technical performance of the molecular methods was assessed through an
      independent masked comparison of each molecular test against the established
      (antigenaemia) test. Scientists performing a particular test were blind to the
      other test results for that sample. Diagnostic and therapeutic impact were
      recorded prospectively for all tests, to include any effect on diagnostic
      certainty, changes to CMV therapy and any other reported impact on patient
      management. The cost of each test was estimated under different laboratory
      conditions. Prospective patients undergoing CMV screening were compared with
      consecutive historical controls in the same unit. Towards the end of the study, a
      survey of all UK virology laboratories was undertaken to identify current CMV
      screening practice and test preferences. In addition, all UK renal transplant
      surgeons and haematology transplant centres were surveyed in order to identify
      current clinical practice and perceptions of the benefits of CMV screening.
      SETTING: Study patients were recruited from University Hospital Wales (UHW),
      Cardiff. Staff in the Cardiff Public Health Laboratory Service virology
      laboratory performed the tests. PARTICIPANTS: A consecutive series of transplant
      patients was recruited to the prospective study over a 42-month period, totalling
      98 renal and 140 haematology patients. A consecutive series of historical
      controls was identified, with 199 renal and 136 haematology patients who
      underwent transplants in the UHW during the 29 months prior to the prospective
      CMV screening trial. INTERVENTIONS: A predefined CMV screening protocol was
      applied to all patients in the prospective trial. Renal patients were tested
      every 4 weeks until 16 weeks post-transplant (five tests in total). Haematology
      patients were tested every 2 weeks until 12 weeks post-transplant, and then every
      4 weeks until 24 weeks (10 tests in total). The assays used for CMV screening
      were as follows: non-molecular test, (1) pp65 antigenaemia assay; molecular
      tests, semi-quantitative in-house polymerase chain reaction (PCR), (2) single
      round (PCR1) and (3) two-round, nested (PCR2); and qualitative commercial tests,
      (4) Roche Amplicor Assay (Amplicor) and (5) pp67 NASBA assay (NASBA). MAIN
      OUTCOME MEASURES: Test failure rates, sensitivity/specificity values and positive
      predictive value (PPV) and negative predictive value (NPV) were measured for each
      assay. The laboratory cost of undertaking various CMV tests was measured and
      other NHS costs associated with false-positive or false-negative test results
      were estimated. The likelihood of CMV disease and the likely impact of positive
      or negative test result on therapy and further investigations were recorded. On
      receipt of the test result, interim outcome measures were recorded to include the
      impact of test result on diagnostic certainty, changes to planned patient
      management (e.g. therapy, investigations) and perceived benefit. All definitive
      diagnoses of CMV disease, prescribing of CMV therapy and interim patient outcome
      at the end of the screening period were recorded. RESULTS: In haematology and
      renal transplant patients, all tests had a similar NPV (0.976--0.997 and 0.935-
      0.995, respectively) when used in CMV screening. PCR1 is the least expensive
      molecular test (7.80-13.70 UK pounds). Commercial tests, NASBA and Amplicor, are
      both more expensive (22.50-34.70 UK pounds NASBA; 23.20-29.20 UK pounds
      Amplicor). Antigenaemia costs 12.50-27.40 pounds depending on staff grade and
      batch size. Quantitative PCR (COBAS) is the most expensive at around 50 UK pounds
      per sample. No clear link between screening test results and CMV prescribing was
      detected; clinicians appear to consider screening results in the context of other
      factors. There was no evidence that the introduction of CMV screening led to
      reductions in CMV deaths or improved transplant success rates. For cost per
      positive test result, PCR1 was the most cost-effective screening test on this
      indicator (renal patients 116 UK pounds per true positive, haematology patients
      518 pounds). Antigenaemia was the least cost-effective screening test (renal
      patients 643 UK pounds per true positive, haematology patients 2475 pounds). Cost
      effectiveness analysis and cost per "beneficial result" (as judged by clinicians)
      confirmed that PCR1 remained the most cost-effective test. Modelling outputs for
      targeted screening protocols also supported this. CONCLUSIONS: The study findings
      offer some evidence that a CMV screening regime is more cost-effective than
      diagnostic testing alone, based on the cost per true positive detected and
      interim outcome such as changes in patient management. However, the study was
      unable to demonstrate any benefits in terms of longer term patient outcomes. If
      CMV screening is introduced, the use of antigenaemia pp65 is clearly less cost
      effective than the use of molecular tests. The study identified the optimum test
      for CMV screening as an in-house molecular test (single-round PCR test). This
      test was less costly to perform and also resulted in lower costs linked to false
      positives and negatives than other tests. The in-house, semi-quantitative test
      was two to three times more cost-effective than the commercial molecular tests
      assessed; however changes to European Union legislation may mean that it may not
      be feasible to use in-house tests. The use of targeted screening (limiting CMV
      screening to high-risk transplants) as opposed to universal screening offers a
      significant improvement in the cost-effectiveness ratio for haematology
      transplant patients, but has limited impact in the case of renal transplants.
      Economic analyses could be expanded to model the cost-effectiveness of more
      frequent screening tests (as reported nationally), and screening in other "at
      risk" groups. Subgroup specific disease groups should be investigated across a
      larger population to allow more accurate modelling of the impact of CMV screening
      on disease progression. Further studies of CMV screening programmes should
      address a range of outcome measures, including patient outcomes.

PMID- 16595080
TI  - Screening for thrombophilia in high-risk situations: systematic review and cost
      effectiveness analysis. The Thrombosis: Risk and Economic Assessment of
      Thrombophilia Screening (TREATS) study.
AB  - OBJECTIVES: To assess the risk of clinical complications associated with
      thrombophilia in three high-risk patient groups: women using oral oestrogen
      preparations, women during pregnancy and patients undergoing major orthopaedic
      surgery. To assess the effectiveness of prophylactic treatments in preventing
      venous thromboembolism (VTE) and adverse pregnancy outcomes in women with
      thrombophilia during pregnancy and VTE in patients with thrombophilia, undergoing
      major orthopaedic surgery. To evaluate the relative cost-effectiveness of
      universal and selective VTE history-based screening for thrombophilia compared
      with no screening in the three high-risk patient groups. DATA SOURCES: Electronic
      databases including MEDLINE, EMBASE, and four other major databases were searched
      up to June 2003. REVIEW METHODS: In order to assess the risk of clinical
      complications associated with thrombophilia, a systematic review of the
      literature on VTE and thrombophilia in women using oral oestrogen preparations
      and patients undergoing major orthopaedic surgery; and studies of VTE and adverse
      obstetric complications in women with thrombophilia during pregnancy was carried
      out. Meta-analysis was used to calculate pooled odds ratios (ORs) associated with
      individual clinical outcomes, stratified by thrombophilia type and were
      calculated for each patient group. To assess the effectiveness of prophylaxis, a
      systematic review was carried out on the use of prophylaxis in the prevention of
      VTE and pregnancy loss in pregnant women with thrombophilic defects and the use
      of thromboprophylaxis in the prevention of VTE in patients with thrombophilia
      undergoing major elective orthopaedic surgery. Relevant data were summarised
      according to the patient groups and stratified according to the types of
      prophylaxis. A narrative summary was provided; where appropriate, meta-analysis
      was conducted. An incremental cost-effectiveness analysis was then carried out,
      from the perspective of the NHS in the UK. A decision analytical model was
      developed to simulate the clinical consequences of four thrombophilia screening
      scenarios. Results from the meta-analyses, information from the literature and
      results of two Delphi studies of clinical management of VTE and adverse pregnancy
      complications were incorporated into the model. Only direct health service costs
      were measured and unit costs for all healthcare resources used were obtained from
      routinely collected data and the literature. Cost-effectiveness was expressed as
      incremental cost-effectiveness ratios (ICERs); an estimate of the cost per
      adverse clinical complication prevented, comparing screening with no screening,
      were calculated for each patient group. RESULTS: In the review of risk of
      clinical complications, 81 studies were included, nine for oral oestrogen
      preparations, 72 for pregnancy and eight for orthopaedic surgery. For oral
      contraceptive use, significant associations of the risk of VTE were found in
      women with factor V Leiden (FVL); deficiencies of antithrombin, protein C, or
      protein S, elevated levels of factor VIIIc; and FVL and prothrombin G20210A. For
      hormone replacement therapy (HRT), a significant association was found in women
      with FVL. The highest risk in pregnancy was found for FVL and VTE, in particular,
      homozygous carriers of this mutation are 34 times more likely to develop VTE in
      pregnancy than non-carriers. Significant risks for individual thrombophilic
      defects were also established for early, recurrent and late pregnancy loss;
      preeclampsia; placental abruption; and intrauterine growth restriction.
      Significant associations were found between FVL and high factor VIIIc and
      postoperative VTE following elective hip or knee replacement surgery. Prothrombin
      G20210A was significantly associated with postoperative pulmonary embolism.
      However, antithrombin deficiency, MTHFR and hyperhomocysteinaemia were not
      associated with increased risk of postoperative VTE. In the review of the
      effectiveness of prophylaxis, based on available data from eight studies, low
      dose aspirin and heparin was found to be the most effective in preventing
      pregnancy loss in thrombophilic women during pregnancy, while aspirin alone was
      the most effective in preventing minor bleeding. All the studies on thrombophilia
      and major elective orthopaedic surgery included in the review of risk
      complications were also used in the review of the effectiveness of
      thromboprophylaxis. However, there were insufficient data to determine the
      relative effectiveness of different thromboprophylaxis in preventing VTE in this
      patient group. For the cost-effectiveness analysis, of all the patient groups
      evaluated, universal screening of women prior to prescribing HRT was the most
      cost-effective (ICER pound6824). In contrast, universal screening of women prior
      to prescribing combined oral contraceptives was the least cost-effective strategy
      (ICER pound202,402). Selective thrombophilia screening based on previous personal
      and/or family history of VTE was more cost-effective than universal screening in
      all the patient groups evaluated. CONCLUSIONS: Thrombophilia is associated with
      increased risks of VTE in women taking oral oestrogen preparations and patients
      undergoing major elective orthopaedic surgery, and of VTE and adverse pregnancy
      outcomes in women with thrombophilia during pregnancy. There is considerable
      difference in the magnitude of the risks among different patient groups with
      different thrombophilic defects. In women who are on combined oral
      contraceptives, the OR of VTE among those who are carriers of the FVL mutation
      was 15.62 (95% confidence interval 8.66 to 28.15). However, in view of the
      prevalence of thrombophilia and the low prevalence of VTE in non-users of
      combined oral contraceptives, the absolute risk remains low. Significant risks
      for VTE and adverse pregnancy outcomes have been established with individual
      thrombophilic defects. Thrombophilic defects including FVL, high plasma factor
      VIIIc levels and prothrombin G20210A are associated with the occurrence of
      postoperative VTE in elective hip or knee replacement therapy. These associations
      are observed in patients who were given preoperative thromboprophylaxis and are,
      therefore, of clinical significance. Universal thrombophilia screening in women
      prior to prescribing oral oestrogen preparations, in women during pregnancy and
      in patients undergoing major orthopaedic surgery is not supported by current
      evidence. The findings from this study show that selective screening based on
      prior VTE history is more cost-effective than universal screening. Large
      prospective studies should be undertaken to refine the risks and establish the
      associations of thrombophilias with VTE among hormone users and in patients
      undergoing orthopaedic surgery. The relative value of a thrombophilia screening
      programme to other healthcare programmes needs to be established.

PMID- 16595081
TI  - A series of systematic reviews to inform a decision analysis for sampling and
      treating infected diabetic foot ulcers.
AB  - OBJECTIVES: To review systematically the evidence on the performance of
      diagnostic tests used to identify infection in diabetic foot ulcers (DFUs) and of
      interventions to treat infected DFUs. To use estimates derived from the
      systematic reviews to create a decision analytic model in order to identify the
      most effective method of diagnosing and treating infection and to identify areas
      of research that would lead to large reductions in clinical uncertainty. DATA
      SOURCES: Electronic databases covering period from inception of the database to
      November 2002. REVIEW METHODS: Selected studies were assessed against validated
      criteria and described in a narrative review. The structure of a decision
      analytic model was derived for two groups of patients in whom diagnostic tests
      were likely to be used. RESULTS: Three studies that investigated the performance
      of diagnostic tests for infection on populations including people with DFUs found
      that there was no evidence that single items on a clinical examination checklist
      were reliable in identifying infection in DFUs, that wound swabs perform poorly
      against wound biopsies, and that semi-quantitative analysis of wound swabs may be
      a useful alternative to quantitative analysis. However, few people with DFUs were
      included, so it was not possible to tell whether diagnostic performance differs
      for DFUs relative to wounds of other aetiologies. Twenty-three studies
      investigated the effectiveness (n = 23) or cost-effectiveness (n = 2) of
      antimicrobial agents for DFUs. Eight studied intravenous antibiotics, five oral
      antibiotics, four different topical agents such as dressings, four subcutaneous
      granulocyte colony stimulating factor (G-CSF), one evaluated oral and topical
      Ayurvedic preparations and one compared topical sugar versus antibiotics versus
      standard care. The majority of trials were underpowered and were too dissimilar
      to be pooled. There was no strong evidence for recommending any particular
      antimicrobial agent for the prevention of amputation, resolution of infection or
      ulcer healing. Topical pexiganan cream may be as effective as oral antibiotic
      treatment with ofloxacin for the resolution of local infection. Ampicillin and
      sulbactam were less costly than imipenem and cilastatin, a growth factor (G-CSF)
      was less costly than standard care and cadexomer iodine dressings may be less
      costly than daily dressings. A decision analytic model was derived for two groups
      of people, those for whom diagnostic testing would inform treatment--people with
      ulcers which do not appear infected but whose ulcer is not progressing despite
      optimal concurrent treatment--and those in whom a first course of antibiotics
      (prescribed empirically) have failed. There was insufficient information from the
      systematic reviews or interviews with experts to populate the model with
      transition probabilities for the sensitivity and specificity of diagnosis of
      infection in DFUs. Similarly, there was insufficient information on the
      probabilities of healing, amputation or death in the intervention studies for the
      two populations of interest. Therefore, we were unable to run the model to inform
      the most effective diagnostic and treatment strategy. CONCLUSIONS: The available
      evidence is too weak to be able to draw reliable implications for practice. This
      means that, in terms of diagnosis, infection in DFUs cannot be reliably
      identified using clinical assessment. This has implications for determining which
      patients need formal diagnostic testing for infection, on whether empirical
      treatment with antibiotics (before the results of diagnostic tests are available)
      leads to better outcomes, and on identifying the optimal methods of diagnostic
      testing. With respect to treatment, it is not known whether treatment with
      systemic or local antibiotics leads to better outcomes or whether any particular
      agent is more effective. Limited evidence suggests that both G-CSF and cadexomer
      iodine dressings may be less expensive than 'standard' care, that
      ampicillin/sulbactam may be less costly than imipenem/cilastatin, and that an
      unlicensed cream (pexiganan) may be as effective as oral ofloxacin. Further
      research is needed to ascertain the characteristics of infection in people with
      DFUs that influence healing and amputation outcomes, to determine whether
      detecting infection prior to treatment offers any benefit over empirical therapy,
      and to establish the most effective and cost-effective methods for detecting
      infection, as well as the relative effectiveness and cost-effectiveness of
      antimicrobial interventions for DFU infection.

PMID- 16595082
TI  - [Molecular diagnosis of retinoblastoma: molecular epidemiology and genetic
      counseling].
AB  - BACKGROUND AND OBJECTIVE: Retinoblastoma, a prototype of hereditary cancer, is
      the most common intraocular tumor in children and a potential cause of blindness
      from therapeutic eye ablation, second tumors in germ line mutation carriers, and
      even death when untreated. The molecular scanning of RB1 in search of germ line
      mutations in 213 retinoblastoma patients from Spain, Cuba, Colombia and Serbia,
      has led to the detection of 106 mutations whose knowledge is important for
      genetic counselling and characterization of phenotypic-genotypic relations.
      PATIENTS AND METHOD: Mutational study (PCR-sequentiation and microsatellites
      analysis) in patients with retinoblastoma, from Spain, Cuba, Colombia and Serbia.
      RESULTS: 45% of mutations, including most of the frame shift (FS), missense (MS)
      and splicing (SP), were new, while all nonsense mutations (NS) corresponded to
      hypermutable sites in RB1. Germ line mutations were found in 22% of unilateral
      sporadic patients. The incidence of SP plus MS mutations in this group of
      patients was greater (p = 0.018) than in bilateral patients. The frequency of SP
      mutations was higher (p = 0.0003) in Spain and France than in Germany and United
      Kingdom, while the incidence of NS mutations was lower (p = 0.0006). SP mutations
      were associated with the low penetrance phenotype and were also overrepresented
      (p = 0.018) in patients with delayed retinoblastoma onset. CONCLUSIONS:
      Mutational scanning of unilateral patients is important for genetic counselling
      and may help decipher the molecular mechanisms leading to low penetrance or
      expressivity. The functional characterization of mutations associated with low
      penetrance or expressivity phenotypes and the molecular classification of tumors
      using multiple expression profiling is important for a better understanding of
      the retinoblastoma pathogenesis.

PMID- 16595083
TI  - [Prevalence and general features of the metabolic syndrome in the Spanish
      hypertensive population].
AB  - BACKGROUND AND OBJECTIVE: Metabolic syndrome (MS) constitutes a risk factor for
      the development of both type 2 diabetes and cardiovascular disease. The aim of
      the present study was to assess the prevalence and clinical characteristics of
      metabolic syndrome in a sample of the hypertensive population. PATIENTS AND
      METHOD: Cross-sectional epidemiological study in 19,039 hypertensive patients
      attended in primary care centres. MS was defined using the National Education
      Cholesterol Program (NCEP) and the International Diabetes Federation (IDF)
      criteria. RESULT: The 44.6% of patients presented MS using NCEP criteria. This
      proportion rose to 61.7% when IDF criteria were applied. Compared with
      hypertensives without MS, those who fulfilled criteria were significantly (p <
      0.0001) older, more frequently women, had higher blood pressure values, a poorer
      blood pressure control (14.4% vs 27.8%) despite the use of more antihypertensive
      drugs, and suffered more frequently of cardiovascular disease. Other significant
      abnormalities included higher serum total cholesterol, uric acid, and a decreased
      estimated glomerular filtration rate. CONCLUSIONS: MS is present in almost half
      of an unselected hypertensive population (two thirds using the newest criteria).
      It is more frequent in women than in men and it is associated with mild
      abnormalities in renal function. MS patients are more refractory to
      antihypertensive treatment, even with a higher number of antihypertensive drugs.

PMID- 16595085
TI  - [Retinoblastoma: genetic and molecular implications].

PMID- 16595084
TI  - [Frequency of thiopurine S-methyltransferase alleles in different ethnic groups
      living in Spain].
AB  - BACKGROUND AND OBJECTIVE: Thiopurine S-methyltransferase (TPMT) metabolizes
      thiopurine drugs regulating their cytotoxicity and clinical response. TPMT
      activity is inherited as an autosomal recessive trait and several mutations in
      the TPMT gene have been identified which correlate with a low activity phenotype.
      A variable number of tandem repeat within the TPMT promoter has been reported to
      modulate the levels of this enzyme activity. The allelic variants of the TPMT
      gene were analyzed in ethnic groups living in Spain. SUBJECTS AND METHOD: The
      frequency of 4 allelic variants of the TPMT gene as well as the genotype in the
      promoter region were analyzed in 138 Spanish blood donors, 95 gypsies and 51
      Basque subjects. RESULTS: In the group of 138 blood donors, we identified: 13
      carriers of a mutated TPMT allele (*3A, *3B, *3C), one homozygous TPMT*3B and a
      compound heterozygote (TPMT*3A/TPMT*3B). In the Basque group, 3 subjects were
      TPMT*3A carriers and one case was a TPMT*3B heterozygote. In the gypsy group one
      subject carried a TPMT*3A allele and 3 were compound heterozygotes
      TPMT*3A/TPMT*3B. The TMPT*3A was the most frequent mutant alelle. As for the
      polymorphic tandem repeat in the 5' flanking region of the TPMT gene, alleles
      with 4 or 5 repeats made up the vast majority (96%) of the chromosomes in the
      control group of Spanish subjects. This figure decreased to 75% in Basques and to
      62% in gypsies, in whom 37% of the alleles contained more than 5 tandem repeats.
      CONCLUSIONS: The frequencies of the mutant TPMT alleles observed in the 3 groups
      are similar to those reported in Caucasian populations.

PMID- 16595086
TI  - [Antipsychotics in the elderly: typical or atypical?].

PMID- 16595087
TI  - [Ethical problems of qualitative research].

PMID- 16595088
TI  - [Food allergy].
AB  - Food allergy is a growing health issue; its prevalence has exponentially
      increased in the past years, and it is situated around 4-5% of the general
      population. Health professionals will frequently have to deal with the management
      of affected patients. Only a minor number of foods cause the majority of allergic
      reactions. In Spain, milk, egg and fish are the most frequent sensitizers in
      children with food allergy; in adults, fruits and nuts, followed by fish and sea
      food are the main food allergens. Clinical manifestations range from mild
      cutaneous reactions to life-threatening anaphylaxis. Therefore, an accurate
      diagnosis is crucial, as well as a correct medical treatment of reactions.
      Furthermore, patients and care-givers should be instructed on allergen avoidance
      and on the use of emergency kits in case of accidental ingestion.

PMID- 16595089
TI  - [Extraesophageal manifestations of reflux disease].

PMID- 16595090
TI  - [Vascular causes of transient global amnesia].

PMID- 16595091
TI  - [PISCIS in turbulent waters?].

PMID- 16595092
TI  - [Azithromycin-induced delirium in on old patient].

PMID- 16595093
TI  - [Immigration and health: a new model of primary care for a new model of
      society?].

PMID- 16595094
TI  - [Screening for breast cancer at forty].

PMID- 16595095
TI  - [Factors affecting primary care referrals to specialised care in the community of
      Madrid].
AB  - OBJECTIVE: Identification of the variables relative to the population
      characteristics and the primary and specialised care services provision which
      determine the referral rates between both levels. DESIGN: Cross-sectional
      ecological study. SETTING: Basic health zones (BHZ) of the Community of Madrid
      (CAM), Spain, 2001. PARTICIPANTS: Population of the CAM. MAIN MEASUREMENTS:
      Dependent variable: population referral rate (PRR) (referrals per BHZ in 2001
      divided by BHZ population). INDEPENDENT VARIABLES: population and their
      characteristics (income, unemployment, educational level, elderly and dependence
      level, marital status, immigrant rates); need of services (care frequency index
      and standardised mortality rate); primary care provision characteristics (number
      of doctors, distribution by age and sex, organisational model, number of years in
      primary care; specialised care provision characteristics (number of laboratory
      specialists, ratio of radio-diagnostic and clinical services doctors). RESULTS:
      The average PRR is 31.9 (0.87) per 100 inhabitants, with a tendency for similar
      values to group into three clusters. Five components which explain 81.87% of the
      variation have been identified: total population, demographic characteristics,
      socioeconomic status, need of services, and social mobility. In the regression
      analysis (R2=0.18), the last 3 reach statistical significance. CONCLUSIONS: The
      PRR is greater in the BHZ with higher levels of need of services and lower levels
      of socioeconomic status and social mobility. There is no relationship with either
      the provision or the organisation of primary care and specialised care. These
      variables should be included in the planning of the provision of services.

PMID- 16595096
TI  - [Possibilities of routine data bases].

PMID- 16595097
TI  - [Analysis of the Educational Program for Self-Care in the Elderly (PECA) for
      improving the quality of life of the elderly].
AB  - OBJECTIVE: To determine the efficacy over 12 months of the educational programme
      on self-care of the elderly (PECA), which covers quality of life, nutritional
      status, and perceived social support of people over 65 living in their own homes.
      DESIGN: Pre-test/post-test experimental study with control group. SETTING: Urban
      population in the Manso Health District (Example, Barcelona), Spain.
      PARTICIPANTS: Persons over 65 living in their own homes, healthy or with chronic
      illnesses characteristic of their age, who had a normal score in the Pfeiffer
      test. A total of 70 subjects (35 per group) were selected and 5 of the control
      group left the study. INTERVENTION: Programme on self-care of the elderly,
      including education on physical activity, nutrition, and social support.
      MEASUREMENTS: Dependent variables were quality of life, measured by the
      Nottingham Health Profile; nutritional status, measured by the Mini-Nutritional
      Assessment (MNA); and social support, measured by the Duke-Unk Functional Social
      Support Scale. RESULTS: The study sample had an average age of 70.9 (SD, 3.1);
      88.2% had self-perception of good health; and 21% lived alone. We only found
      statistically significant differences between pre- and post-intervention
      observations in nutritional status (P=.001). CONCLUSION: Despite a statistically
      significant difference in the variable of nutritional status, the difference was
      not "clinically" relevant. The ineffectiveness of the intervention is due to our
      starting from a very homogeneous sample, which had good health status and well
      established social networks.

PMID- 16595098
TI  - [Effectiveness of a programme of intensive tobacco counselling by nursing
      professionals].
AB  - OBJECTIVE: To determine the effectiveness of a systematic intensive tobacco
      counselling programme conducted by nursing professionals. DESIGN: Randomised
      clinical trial with control. SETTING: Primary care nursing and medical
      consultations. PARTICIPANTS: Smokers requesting help in our centre's medical
      clinics during the recruitment period, up to the sample size required (125).
      Inclusion criteria were: aged between 18 and 70, people who smoked during the
      preceding month any number of cigarettes a day, and a score over 7 on the
      Richmond test. INTERVENTIONS: The patients recruited were randomised, according
      to the clinic from which they came, to the group that received brief counselling
      from the doctor (control group) or to the group that received brief counselling
      plus nursing follow-up (intervention group). Follow-up visits were programmed in
      this latter group for up to 3 months after giving up smoking. MAIN MEASUREMENTS:
      Abstinence at 12 and 24 months. RESULTS: The effectiveness of the intervention
      considered as the rate of abstinence at 12 months was 13.8% (95% CI, 6.5-24.7) in
      the control group and 6.7% (95% CI, 1.8-16.2) in the intervention group, with no
      significant differences between the two. CONCLUSIONS: In smokers seen in primary
      care, the effectiveness of a programme of intensive tobacco counselling by
      nursing staff is no more effective than the doctor's brief, one-off counselling.
      Brief counselling has a better cost-effectiveness relationship than intensive
      counselling.

PMID- 16595099
TI  - [Definition and validation of quality indicators of prescription in primary
      care].
AB  - OBJECTIVE: To define and validate a battery of prescription indicators on the use
      of anti-hypertensives, lipid-lowerers, diabetes drugs, and insulin, as
      measurements of family doctors' quality of prescription in primary health care.
      DESIGN: Transversal, descriptive study. SETTING: Two primary care health
      districts, Camas and Sierra Norte, Spain. PARTICIPANTS: Eighty three family
      doctors, 94.32% of the doctors in the study area. DEFINITION AND VALIDATION OF
      INDICATORS: To construct the prescription indicators, we used evidence found in
      the scientific bibliography available. To validate it, we analysed its
      statistical relationship with a series of selected clinical tests, collected from
      the clinical records. RESULTS: For each doctor, there was a statistically
      significant relationship between the index of quality of prescription and the
      clinical quality seen in the records (P=.004). The variables of age, sex, and
      training fine-tuned the model. CONCLUSIONS: There is a statistically significant
      relationship between a good prescription indicator and proper control of
      intermediate health variables.

PMID- 16595100
TI  - [Inspection validation of prescription: guaranteeing proper use of medicines or a
      cost-control measure?].
AB  - OBJECTIVE: To assess the views of primary care physicians (PCPs) in Spain
      regarding the purpose of inspection validation of prescriptions (IVP) and its
      impact on prescription and patients, as well as doctors' acceptance of this
      measure. DESIGN: Cross-sectional study through a telephone survey. SETTING:
      Primary care centres. PARTICIPANTS: PCPs prescribing oral diabetes drugs
      requiring IVP, or who were familiar with IVP. METHODS: Telephone survey conducted
      in October-November, 2003, of 1471 PCPs. Sample size was calculated to ensure
      accuracy to 10% in each autonomous region. RESULTS: 91.9% of the 1600 PCPs
      contacted who agreed to participate in the study met the inclusion criteria. On
      average, they prescribed 30.6 drugs requiring IVP per month (95% CI, 28.0-33.2),
      requiring an additional 4.6 minutes per prescription (95% CI, 4.4-4.8). 64.7% of
      PCPs increased their clinical work-time for this reason. 71.3% of PCPs (95% CI,
      69.0-73.6) considered IVP an obstacle when prescribing a drug that requires it
      and 44.5% (95% CI, 42.0-47.0) believed that the IVP puts patients' right to
      receive the appropriate treatment at risk. PCPs considered that inspectors refuse
      authorization of their prescriptions requiring IVP for administrative (43.3%),
      economic (36.5%), or clinical (13.2%) reasons. 87.1% of PCPs stated that medical
      prescription is a sufficient control system and that IVP is not necessary for
      medicines for diseases managed in primary care such as Type-2 DM. 76.2% believed
      that the health authorities imposed the IVP requirement for some oral diabetes
      drugs in order to control expenditure on drugs, and 75.4% supported its
      withdrawal. CONCLUSION: According to PCPs, the objective of the IVP is mainly
      economic and may affect negatively their clinical practice and patients.
      Therefore, in general, they do not support it, at least for drugs for diseases
      mainly managed in primary care.

PMID- 16595102
TI  - [Evaluation of the efficacy of a comprehensive programme of secondary prevention
      of cardiovascular disease in primary care: the PREseAP Study].
AB  - OBJECTIVES: To assess the efficacy of a comprehensive secondary prevention
      programme to reduce morbidity and mortality in patients who have suffered a
      cardiovascular (CV) event; to control CV risk factors and prophylactic treatment
      in order to prevent recurrence; and to improve the quality of life of patients
      with cardiovascular disease. DESIGN: Randomised, pragmatic, open clinical trial
      in primary care. SETTING: A total of 42 primary care centres of 8 different areas
      in Spain. PARTICIPANTS: Men and women below 86 years old, diagnosed with coronary
      disease and/or stroke and/or peripheral vascular disease in the preceding year,
      and who have no serious or terminal disease. INTERVENTION: Primary care centres
      will be randomised to following usual care (control group), or to following a
      comprehensive programme of secondary prevention (intervention group). MAIN
      MEASUREMENTS: Cardiovascular fatal events, cardiovascular non-fatal events, total
      mortality and health-related quality of life (SF-36).

PMID- 16595101
TI  - [Codevelopment and health. Prevention of HIV transmission in Ghana: the Brothers
      in Work Programme].
AB  - OBJECTIVE: To design a health programme, as part of a codevelopment programme,
      aimed at reducing the occurrence of HIV-AIDS in a rural African population.
      DESIGN: The Catalan Society of Community and Family Medicine developed the
      Brothers in Work Health Programme (BWP) through a working party of Spanish and
      Ghanaian doctors. The programme has two consecutive stages. The first ("being
      safe") aims to stop transmission of the virus caused by accidents with health
      material. The second, intervention stage ("being active") focuses on introducing
      voluntary antenatal screening for HIV, counselling and a protocol for
      administering nevirapine to a cohort of 600 seropositive women whilst giving
      birth. The results will be compared with another cohort of 600 seronegative
      pregnant women. SETTING: Three Area Hospitals in the Central Region of Ghana.
      PARTICIPANTS: 876,000 people from 3 districts. MAIN MEASUREMENTS: Assessment of
      HIV-AIDS prevalence and survival of newborns at 18 months. Monitoring of the cost
      efficiency relationship of the interventions. RESULTS: Estimated direct costs
      are: a) for diagnosis of each seronegative patient, 2.43 euros (1.75 co-payment),
      and b) for diagnosis, counselling, and nevirapine treatment of each seropositive
      patient, 6.6 euros (4.65). Estimated cost-efficiency relationship of the
      programme is: a) for every patient diagnosed, counselled and included in the
      programme, 23.5 euros (15.3), and b) for each case of intra-delivery infection of
      baby avoided, 20.03 euros (15.5). HIV transmission to 54 children would be
      avoided (9% of the deliveries of seropositive women; 6.3 of the total women
      tested). CONCLUSIONS: The BWP has a good cost/benefice relationship in the
      interruption of HIV transmission.

PMID- 16595104
TI  - [Under-use of platelet antiaggregants in patients with cardiovascular disease].

PMID- 16595105
TI  - [Residents give their views on semFYC: benefits and reasons for joining].

PMID- 16595106
TI  - [Detection of psychiatric and social risks in health professionals in a health
      district].

PMID- 16595107
TI  - [Calculation of the susceptible population for a new campaign of chicken-pox
      vaccination].

PMID- 16595108
TI  - [Considerations on the professional quality of life of primary care workers in
      Madrid].

PMID- 16595109
TI  - [Why do we say self-management when we should say self-analysis?].

PMID- 16595110
TI  - [Photodynamic therapy in dermatology].
AB  - Photodynamic therapy (PDT) is a therapeutic modality based on the photooxidation
      of biological materials induced by a photosensitizer, which selectively locates
      itself in certain tumorous cells or tissues, so that when illuminated by a light
      of the right length and at a sufficient dose, these cells are destroyed. In
      dermatology, PDT with topical 5-aminolevulinic acid or 5-methyl aminolevulinate
      is very effective in the treatment of actinic keratoses, basal cell carcinomas
      and Bowen's disease. In addition, very promising results have been obtained in
      inflammatory pathologies like morphea or sarcoidosis, infections like warts, and
      cosmetic processes such as photoaging, among others. This article reviews the
      most significant aspects of PDT in dermatology. First of all, we will review the
      basic fundamentals of photodynamic treatment. Next, we will outline its clinical
      applications in dermatology, both in oncological applications and all those
      dermatological processes in which PDT may play a role in their management. We
      will also discuss its promising cosmetic application in the treatment of
      photoaging. We will complete the review with photodiagnosis and the different non
      invasive ways to monitor the effectiveness of PDT.

PMID- 16595111
TI  - [Update in the treatment of herpes zoster].
AB  - The systemic treatment of herpes zoster shortens the healing process, and
      prevents or alleviates pain and other acute or chronic complications, especially
      when it is administered in the first 72 hours after symptoms appear. This
      treatment is especially indicated in patients over the age of 50 and in those
      who, regardless of age, have head and neck involvement, especially in herpes
      zoster ophthalmicus. The drugs approved in Europe for the systemic treatment of
      herpes zoster are aciclovir, valaciclovir, famciclovir and brivudine. Brivudine
      shows greater effectiveness against the varicella-zoster virus than aciclovir and
      its derivatives, and can be given just once a day for seven days, compared to
      multiple doses of the latter. As opposed to the others, brivudine is a non
      nephrotoxic drug that should not be administered to immunodepressed patients or
      to those being treated with 5-fluorouracil. The treatment of herpes zoster to
      reduce pain should be combined with analgesics and neuroactive agents
      (amitriptyline, gabapentin, etc). While corticosteroids are of dubious efficacy
      in the treatment of post-herpes neuralgia, the intensity and duration of the pain
      can be reduced with some topical treatments (capsaicin, lidocaine patches, etc).
      Finally, this review discusses treatment guidelines for special locations
      (cranial nerves) and different subpopulations (children, pregnant women,
      immunodepressed patients, etc).

PMID- 16595112
TI  - [Porphyria cutanea tarda in a dialyzed female patient].
AB  - Dermatological disorders are a frequent finding in patients with renal
      insufficiency. Porphyria cutanea tarda, pseudoporphyria, phototoxicity or
      concurrent bullous diseases may cause the appearance of lesions with liquid
      content in patients in dialysis. We describe the case of a female patient in
      dialysis who developed bullous lesions. The clinical and laboratory findings were
      initially compatible with the suspicion of pseudoporphyria, but the finding of
      some frankly elevated levels of porphyrins in serum, urine and feces confirmed
      the diagnosis of porphyria cutanea tarda. Porphyria cutanea tarda and
      pseudoporphyria present with common clinical manifestations. However, the levels
      of porphyrins in plasma, urine and feces in pseudoporphyria are normal or
      slightly elevated.

PMID- 16595113
TI  - [Diffuse cutaneous reticulohistiocytosis].
AB  - The reticulohistiocytoses make up a heterogeneous group of diseases whose origin
      lies in an accumulation of cells of histiocytic lineage in different tissues and
      primarily in the skin. Three main clinical forms have been described
      (multicentric, solitary, diffuse cutaneous), which present with identical
      histological, ultrastructural and immunohistochemical characteristics. We present
      a case of diffuse cutaneous reticulohistiocytosis, which is the least common
      clinical pattern in the spectrum of this disease.

PMID- 16595114
TI  - [Genital artefact ulcers appearing simultaneously in a couple].
AB  - Genital ulcers may be due to a number of causes, with the most frequent ones
      being of infectious, tumorous and physical etiology. The coexistence of genital
      lesions in a couple makes it necessary to rule out sexual transmission as a first
      option, as it is not always the cause. We present the case of a 78 and 73-year
      old couple, both of whom presented with genital ulcers which had been developing
      for months and which began to manifest simultaneously. The negative results in
      the tests performed, the exclusion of other likely causes and the favorable
      evolution of the lesions suggest self-inflicted ulcers as a probable diagnosis,
      an infrequent form of presentation of "folie a deux". Despite its infrequent
      occurrence, dermatitis artefacta is a cause that should always be included in the
      differential diagnosis of any skin lesion, as it often goes unnoticed because of
      its many clinical presentations.

PMID- 16595116
TI  - [Papillary dermal elastolysis similar to pseudoxanthoma elasticum].
AB  - Papillary dermal elastolysis similar to pseudoxanthoma elasticum is an
      elastolytic disorder characterized by cutaneous lesions on the neck and in the
      supraclavicular region that are clinically similar to pseudoxanthoma elasticum,
      with no systemic complications. The histological examination shows a loss of
      elastic fibers in the papillary dermis. We report a case in a 76-year-old woman
      with typical lesions on the neck.

PMID- 16595115
TI  - [Cryoglobulinemic syndrome: presentation of four cases with skin involvement].
AB  - Cryoglobulins are serum immunoglobulins that precipitate reversibly when the
      serum is cooled below 371 degrees C. In cryoglobulinemic syndrome, a multitude of
      organs can be involved, but many patients suffer from a moderate, chronic disease
      consisting of palpable purpura, arthralgia and fatigue. Skin involvement is
      especially useful in aiding early recognition of this entity. We present four
      patients with cryoglobulinemic syndrome and skin lesions, in whom it was not
      possible to find an etiological or associated factor. We discuss the
      etiopathogenesis, clinical and pathological findings, treatment and prognosis of
      this entity.

PMID- 16595117
TI  - [Bilateral ossification of the auricular cartilage].
AB  - Auricular petrification is an infrequent finding in which the ears become
      completely or partially rigid. The most frequent cause is the calcification of
      the auricular cartilage and, infrequently, auricular ossification. Ossification
      may be due to hypothermia, physical factors, inflammatory processes and different
      endocrinopathies. Severe hypothermia is the most frequent cause. We present a
      case of bilateral ossification of the auricular cartilage secondary to
      hypothermia.

PMID- 16595118
TI  - [Autosomal dominant punctate palmoplantar keratoderma].
AB  - Hereditary punctate palmoplantar keratoderma or Buschke-Fisher-Brauer disease is
      a rare form of keratoderma that follows a pattern of autosomal dominant
      inheritance with variable penetrance. The age of onset is usually between 12 and
      30 years of age. Clinically, it is characterized by the gradual appearance of
      multiple punctate hyperkeratotic papules, irregularly distributed on the palms
      and soles, as well as by its possible association with several diseases,
      primarily with malignant processes. We present the case of a 43-year-old male
      patient with this disease, with no other associated symptoms, who had a first
      degree relative who was affected and died of colon cancer. We also discuss the
      differential diagnosis with other nosologic entities.

PMID- 16595119
TI  - [Linear Darier disease].
AB  - Darier disease is a genodermatosis with a pattern of autosomal dominant
      inheritance, which occasionally presents by following a linear or segmental
      pattern. We present the case of a 22-year-old woman who had presented for three
      years with small, linearly distributed, yellowish-brown papules on the right
      lower extremity, with no other skin, mucous membrane or appendage involvement.
      She had no personal or family history of any interest. Histologically, suprabasal
      acantholysis and abundant dyskeratotic cells were seen. All of this data led to
      the diagnosis of linear Darier disease.

PMID- 16595120
TI  - [Erythematous nodule on the back of the hand].

PMID- 16595121
TI  - [Giant ulcer on the back].

PMID- 16595122
TI  - [Contribution to acneiform eruptions by epidermal growth factor receptor
      inhibitors].

PMID- 16595123
TI  - [Unilateral nevus comedonicus: efficacy after treatment with 12% ammonium
      lactate].

PMID- 16595124
TI  - Fenofibrate activates the biochemical pathways and the de novo expression of
      genes related to lipid handling and uncoupling protein-3 functions in liver of
      normal rats.
AB  - Fibrates (anti-hyperlipidemic agents) enhance the mRNA expression of uncoupling
      protein 2 (UCP2) in the liver and that of uncoupling protein 3 (UCP3) in skeletal
      muscle in standard-diet-fed rats and induce a de novo expression of UCP3 (mRNA
      and protein) in the liver of high-fat-fed rats. Here, we report that in the liver
      of normal rats, fenofibrate induces a de novo expression of UCP3 and a 6-fold
      increase in UCP2 mRNA, whereas UCP2 protein was not detectable. Indeed, we
      evidenced an ORF in UCP2 exon 2 potentially able to inhibit the expression of the
      protein. Fenofibrate increases the expression and activity of hepatic enzymes and
      cofactors involved in lipid handling and UCP3 activity and, as is the case for
      UCP3, induces other muscle-specific genes (e.g., Carnitine palmitoyl transferase
      1b and Ubiquinone biosynthesis protein COQ7 homolog). In addition, we
      demonstrated that in mitochondria from fenofibrate-treated rats a palmitoyl
      carnitine-induced GDP-sensitive uncoupling takes place, involving UCP3 rather
      than other uncouplers (i.e., UCP2 and Adenine Nucleotide Translocase). Thus, the
      liver of fenofibrate-treated standard-diet- fed rat is a useful model for
      investigations of the biochemical functions of UCP3 and allowed us to demonstrate
      that fenofibrate programs a gene-expression pattern able to modulate lipid
      handling and UCP3 activation.

PMID- 16595126
TI  - Contribution of endothelin-1 to the enhanced carotid body chemosensory responses
      induced by chronic intermittent hypoxia.
AB  - Chronic intermittent hypoxia (CIH) enhances carotid body (CB) chemosensory
      responses to acute hypoxia. We tested the hypothesis that endothelin-1 (ET-1), an
      excitatory modulator of CB chemoreception may contribute to the enhanced CB
      chemosensory responses in cats exposed to cyclic hypoxic episodes repeated during
      8 h for 4 days. Accordingly, we measured the ET-1 immunoreactivity (ET-ir) in the
      CB and plasma. Using a perfused CB preparation, we studied the effects of
      exogenous ET-1 and bosentan, a non-selective endothelin receptor type A and B
      antagonist, on the frequency of chemosensory discharges (f(x)) during normoxia,
      mild and severe hypoxia. We found that CIH increased ET-ir in the CB by
      approximately 10-fold leaving ET-1 plasma levels unchanged. Application of ET-1
      to control and CIH-treated CBs produced long-lasting dose-dependent increases in
      f(x), although the dose-response curve showed a rightward-shift in the CIH
      treated CBs. CIH increased baseline f(x) and hypoxic chemosensory responses,
      which were reduced by 50 microM bosentan in CBs from CIH-treated cats. Present
      results suggest that a local increase of ET-1 in the CB may contribute to the
      enhanced chemosensory responses induced by CIH predominantly through a vasomotor
      mechanism.

PMID- 16595125
TI  - The BH3-only protein, PUMA, is involved in oxaliplatin-induced apoptosis in colon
      cancer cells.
AB  - Oxaliplatin, the first line chemotherapeutic of colon cancer, induces damage to
      tumors via induction of apoptosis. PUMA (p53 up-regulate modulator of apoptosis)
      is an important pro-apoptotic member of Bcl-2 family and regulated mainly by p53.
      Here we investigated the role of PUMA in oxalipaltin-induced apoptosis and the
      potential mechanism. We showed that oxaliplatin-induced PUMA expression in a time
      and dose-dependent manner and suppression of PUMA expression by stable
      transfecting anti-sense PUMA plasmid decreased oxaliplatin-induced apoptosis in
      colon cancer cells. By abrogating the function of p53, we further demonstrated
      that the induction was p53-independent. We also found that oxaliplatin could
      inactivate ERK and suppression of ERK activity by its specific inhibitor
      (PD98059), and dominant negative plasmid (DN-MEK1) enhanced the oxaliplatin
      induced PUMA expression and apoptosis in a p53-independent manner. Taken
      together, our data suggest that PUMA plays an important role in oxaliplatin
      induced apoptosis and the induction could be both p53-dependent and p53
      independent. Moreover, PUMA expression and apoptosis in oxaliplatin-treated colon
      cancer cells could be regulated partly by ERK inactivation. Identification of the
      molecular components involved in regulating the cellular sensitivity to
      oxaliplatin may provide potential targets for development of novel compounds that
      may be useful in enhancement of oxaliplatin cytotoxicity in p53 deficient colon
      cancer.

PMID- 16595127
TI  - An ERP study of preparatory and inhibitory mechanisms in a cued saccade task.
AB  - The present study uses event-related potentials (ERPs) to investigate the
      neurophysiological correlates of the mechanisms involved in selection of
      locations for saccades. Participants performed a task in which both target and
      distractor locations were cued on a trial-by-trial basis. Participants were
      instructed to make an eye movement to the cued target location and to ignore
      elements at the distractor location. This experimental set-up allowed the
      investigation of the mechanisms involved in the top-down preparation and
      inhibition of locations for an eye movement. When comparing responses to leftward
      and rightward pointing cues, we observed an early directing attention negativity
      (EDAN) and an anterior directing attention negativity (ADAN) effect in the cue
      target interval. These effects were similar to those observed in studies
      investigating attentional allocation, suggesting a close link between shifts of
      spatial attention and the preparation of eye movements. These components were
      followed by a late widespread contralateral negativity (LDAN) that was assumed to
      reflect both the oculomotor programming of the upcoming eye movement as well as
      attentional orienting. Furthermore, a new component was observed related to top
      down inhibition of the distractor location. In response to the distractor cue, an
      early positivity above the right hemisphere (RLIP) was revealed. Finally, no
      modulations of early target-evoked ERP components were observed, suggesting that
      these components are unaffected when no further processing is required at the
      cued location.

PMID- 16595128
TI  - An increase of blood squamous cell carcinoma antigen in Pseudomonas aeruginosa
      spondylitis.
AB  - Squamous cell carcinoma antigen (SCCA) is traditionally engaged for detecting and
      following up malignancy from a squamous cell origin. We encountered an unusual
      increase of blood SCCA but no other cancer markers in a patient associated with
      an infective lumbar spondylitis due to Pseudomonas aeruginosa. An overshooting of
      Th1 expression, such as tumor necrosis factor alpha, bumped up by his uremia as a
      result of P. aeruginosa infection may hasten SCCA. Therefore, SCCA might
      additionally serve as a serological marker for infection besides squamous cell
      cancer, and its false-positive increase also highlights the appropriateness of
      tumor marker screening.

PMID- 16595129
TI  - Incomplete pediatric reference intervals for the management of patients with
      inborn errors of metabolism.
AB  - OBJECTIVES: To evaluate the status of pediatric reference intervals for several
      biomarkers of inborn errors of metabolism (IEM). INTRODUCTION: There are several
      biomarkers that are used in many laboratories that specialize in biochemical
      genetics. Among them, there are acylcarnitines, total carnitine, amino acids,
      essential fatty acids, phytanic acid and very long chain fatty acids. These tests
      are key to exclusion or inclusion of an IEM, therefore appropriate age-related
      references intervals are crucial. A detailed review of each selected analyte is
      given. RESULTS: Published reference intervals do not always address the
      dependency of age, gender, or ethnic background; they are not established for
      newer laboratory methodologies and are derived from a limited number of healthy
      controls for most markers. CONCLUSIONS: To address the gap in pediatric reference
      intervals, the Canadian research project (CALIPER database) will establish
      comprehensive reference intervals for acylcarnitines, total carnitine, amino
      acids, essential fatty acids, phytanic acid, and very long chain fatty acids. All
      the tests will be limited to whole blood, plasma and serum samples.

PMID- 16595130
TI  - Regulation of Ci and Su(fu) nuclear import in Drosophila.
AB  - The Hedgehog (Hh) signal transduction pathway plays a central role in the
      development of invertebrates and vertebrates. While much is known about the
      pathway, the role of Suppressor of fused (Su(fu)), a component of the pathway's
      signaling complex has remained enigmatic. Previous studies have linked Su(fu) to
      the cytoplasmic sequestration of the zinc finger transcription factor, Cubitus
      interruptus (Ci), while other studies suggest a role in modulating target gene
      expression. In examining the cell biology of the pathway, we have found that like
      its vertebrate homologue, Drosophila Su(fu) enters the nucleus. Furthermore, we
      find that the nuclear import of Su(fu) occurs in concert with that of Ci in
      response to Hh signaling. Here, we examine the mechanism by which Su(fu)
      regulates Ci import by investigating the importance of the Ci nuclear
      localization signal (NLS) and the effect of adding an additional NLS. Finally, we
      demonstrate that Ci can bring Su(fu) with it to a multimerized Ci DNA binding
      site. These results provide a basis for understanding the dual roles played by
      Su(fu) in the regulation of Ci.

PMID- 16595131
TI  - D-six4 plays a key role in patterning cell identities deriving from the
      Drosophila mesoderm.
AB  - Patterning of the Drosophila embryonic mesoderm requires the regulation of cell
      type-specific factors in response to dorsoventral and anteroposterior axis
      information. For the dorsoventral axis, the homeodomain gene, tinman, is a key
      patterning mediator for dorsal mesodermal fates like the heart. However,
      equivalent mediators for more ventral fates are unknown. We show that D-six4,
      which encodes a Six family transcription factor, is required for the appropriate
      development of most cell types deriving from the non-dorsal mesoderm - the fat
      body, somatic cells of the gonad, and a specific subset of somatic muscles.
      Misexpression analysis suggests that D-Six4 and its likely cofactor, Eyes absent,
      are sufficient to impose these fates on other mesodermal cells. At stage 10, the
      mesodermal expression patterns of D-six4 and tin are complementary, being
      restricted to the dorsal and non-dorsal regions respectively. Our data suggest
      that D-six4 is a key mesodermal patterning mediator at this stage that regulates
      a variety of cell-type-specific factors and hence plays an equivalent role to
      tin. At stage 9, however, D-six4 and tin are both expressed pan-mesodermally. At
      this stage, tin function is required for full D-six4 expression. This may explain
      the known requirement for tin in some non-dorsal cell types.

PMID- 16595132
TI  - Blocking tumor necrosis factor-alpha inhibits folic acid-induced acute renal
      failure.
AB  - Systemic administration of mice with folic acid (FA) has been used for studying
      the pathogenesis of acute renal failure. However, the molecular mechanisms by
      which FA induces acute renal failure remain poorly understood. We found that CD-1
      mice treated with FA developed acute renal failure characterized by increased
      blood urea nitrogen, necrosis, and apoptosis of tubular epithelial cells.
      Compared to control mice, tumor necrosis factor-alpha (TNF-alpha) was markedly
      elevated in blood and kidneys of these FA-treated mice, accompanied by markedly
      reduced expression of anti-apoptotic protein BclxL in their kidneys. In vivo
      administration of FA-treated CD-1 mice with neutralizing anti-TNF-alpha antibody
      restored the expression of BclxL in kidneys and inhibited the necrosis and
      apoptosis of renal tubular epithelial cells, leading to the amelioration of acute
      renal failure. In ex vivo cultures, we found that FA enhanced production of TNF
      alpha, decreased expression of BclxL protein, and induced apoptosis of mouse
      cortical tubule (MCT) cells. Addition of neutralizing anti-TNF-alpha antibody,
      but not control IgG, in the cultures markedly blocked the apoptotic death of FA
      treated MCT cells and restored expression of BclxL to the same levels as those
      MCT cells cultured in the absence of FA. All these results suggest that TNF-alpha
      is a critical inflammatory cytokine responsible for FA-mediated acute renal
      failure. Furthermore, in vivo administration of anti-TNF-alpha antibody may be
      proved as an effective approach for acute renal failure prevention and treatment.

PMID- 16595133
TI  - Multiple signaling pathways mediate compaction of collagen matrices by EGF
      stimulated fibroblasts.
AB  - Fibroblasts stimulated by EGF within collagen matrices generate contraction
      forces that are likely of importance to cell migration and matrix compaction
      during wound healing. We have employed an in vitro fibroblast-embedded collagen
      matrix compaction assay to ascertain signaling pathway components downstream of
      EGFR activation leading to generation and transmission of contractile force. EGF
      compacts this floating collagen matrix to a similar extent as PDGF. We
      demonstrate that compaction requires EGFR kinase activity, yet is maximal in
      magnitude at intermediate EGF concentrations. This suggests that transmission of
      EGFR-induced contractile force to the matrix can be mitigated by consequent anti
      adhesive effects of EGFR signaling in a dose-dependent manner. Treatment with
      pharmacological inhibitors demonstrated involvement of the signaling components
      extracellular signal-regulated kinase (ERK), Rho kinase, and myosin light chain
      kinase (MLCK) in the force generation and/or transmission process. Moreover,
      treatment with the pan-calpain inhibitor ALLN and isoform-specific downregulation
      of m-calpain (CAPN2) using RNA interference determined m-calpain to be a key
      component of the EGF-induced force response. ALLN treatment modulated the
      compaction response in a biphasic manner, enhancing matrix deformation to the
      greatest extent at intermediate concentrations. Our findings have thus identified
      key signals downstream of EGFR, which integrate in a complex manner to generate
      and transmit contractile forces to yield matrix deformation.

PMID- 16595134
TI  - Digit ratio (2D:4D) and the spatial representation of magnitude.
AB  - Digit ratio (as a putative indicator of prenatal androgen exposure) is related to
      a range of sexually dimorphic abilities, including spatial skills and
      mathematical ability. This study examined a phenomenon known as the SNARC effect
      (Spatial Numerical Association of Response Codes), which is taken as evidence of
      a mental representation of magnitude along a left-right-oriented number line,
      with low magnitudes associated with the left side of space, and high numbers with
      the right side of space. Participants made a parity judgement of numbers with
      responses made with a left key to odd numbers and a right key to even numbers.
      This was reversed for a second block of trials. Response times to numbers one to
      nine with both the right and left hand were calculated, and regression analyses
      conducted to analyse whether lower magnitudes were responded to faster with the
      left hand and higher magnitudes with the right hand. Participants with lower
      (more masculine) digit ratios on the right hand showed a stronger SNARC effect
      compared to participants with high digit ratios. This pattern of results was also
      found when the analyses were conducted separately for men and women. Results from
      left hand digit ratios indicated that only low digit ratio females showed a
      significant SNARC effect. These findings add to a growing literature on the
      relationship between digit ratio and cognitive abilities; in this case, simple
      cognitive representations that are accessed automatically rather than complex
      skills such as mental rotation or "mathematics" where a variety of solution
      strategies may be utilised.

PMID- 16595135
TI  - Trace determination of beta-lactam antibiotics in surface water and urban
      wastewater using liquid chromatography combined with electrospray tandem mass
      spectrometry.
AB  - A sensitive and reliable method using liquid chromatography-electrospray tandem
      mass spectrometry has been developed and validated for the trace determination of
      beta-lactam antibiotics in natural and wastewater matrices. Water samples were
      enriched by solid-phase extraction. The analytes included amoxicillin (AMOX),
      ampicillin (AMP), oxacillin (OXA), cloxacillin (CLOX) and cephapirin (CEP).
      Average recoveries of beta-lactams (BLs) in fortified samples were generally
      above 75% (except amoxicillin) with the standard deviations lower than 10% in
      water matrices. Amoxicillin was not quantified due to poor recovery (less than
      40%) in the investigated water matrices. Matrix effects were found to be minimal
      when measuring these compounds in water matrices. The accuracy, within- and
      between-run precision of the assay fell within acceptable ranges of 15% absolute.
      The method detection limit (MDL) was estimated to range between 8 and 10 ng/L in
      surface water, 13 and 18 ng/L in the influent and 8 and 15 ng/L in the effluent
      from a wastewater treatment plant. A large number of actual water samples were
      analyzed using this method in order to evaluate the occurrence of the beta
      lactams in a river and a wastewater treatment plant in northern Colorado. Most of
      the samples were negative for all analytes. These compounds were found at 15-17
      ng/L in the three influent samples and at 9-11 ng/L in three surface water
      samples out of a total of 200 samples. This indicates that contamination by beta
      lactam antibiotics is of minor importance to the small mixed-watershed.

PMID- 16595136
TI  - Different retention behavior of structurally diverse basic and neutral drugs in
      immobilized artificial membrane and reversed-phase high performance liquid
      chromatography: comparison with octanol-water partitioning.
AB  - The retention behavior of 43 structurally diverse neutral and basic drugs in
      immobilized artificial membrane chromatography was investigated and compared to
      the reversed-phase retention and octanol-water partitioning. IAM chromatography
      was performed using morpholinepropanesulfonic acid (MOPS) or phosphate buffer
      saline (PBS) at pH 7.4 as the aqueous component of the mobile phase. The
      differences in the retention factors were attributed to increased electrostatic
      interactions in the MOPS environment, dependent on the fraction of charged
      species. Electrostatic interactions were found to play a key role in the
      relationships with reversed-phase retention factors determined under two
      different mobile phase conditions as well as in the relationships with
      lipophilicity data. IAM retention factors correlated better with octanol-water
      partition coefficients log P than with log D(7.4), as a result of the
      contribution of electrostatic forces in IAM retention. With log D(7.4) the
      relationships were improved when the fraction of charged species was taken into
      consideration. In any case the regression coefficient of log P or log D(7.4) was
      considerably lower than 1 reflecting the reduced hydrophobic environment of the
      IAM stationary phase. The different data sets were submitted to principal
      component analysis for further exploration of their similarities/dissimilarities.

PMID- 16595137
TI  - Novel stationary phases for high-performance liquid chromatography analysis of
      cyclodextrin derivatives.
AB  - Novel stationary phases were prepared for separation of cyclodextrins and
      cyclodextrin derivatives by bonding substituted aromatic groups (phenyl and
      naphthyl) to the silica gel matrix. Both the electron-withdrawing (nitro) and the
      hydrogen-donor/acceptor (amide or carbamide) substituents of the phenyl group
      play essential role in the separation of cyclodextrins and cyclodextrin
      derivatives. On the basis of the comparison of experimental data obtained on
      different columns the N-(4-nitrophenyl)-carbamide group bonded silica gel
      stationary phase was selected as the most effective one for analysis of
      cyclodextrin derivatives. Improved separation potency was observed for
      hydroxypropylated, methylated and several other cyclodextrin derivatives compared
      with the previously and presently used stationary phases. Owing to the strong
      retention of cyclodextrins and its derivatives on the selected column, detection
      of their decomposition products was easily achieved. Determination of
      unsubstituted, natural cyclodextrin as an impurity in the cyclodextrin
      derivatives was implemented. Identification and characterization of cyclodextrin
      derivatives in industrial products could also be performed.

PMID- 16595138
TI  - Molecularly imprinted polymers with a streamlined mimic for zearalenone analysis.
AB  - Molecularly imprinted polymers (MIPs) with selective recognition properties for
      zearalenone (ZON), an estrogenic mycotoxin, and structurally related compounds
      have been prepared using the non-covalent imprinting approach. A rationally
      designed ZON analogue, cyclododecyl 2,4-dihydroxybenzoate (CDHB), that exhibits
      resemblance to ZON in terms of size, shape and functionality has been synthesized
      and used as template for MIP preparation instead of the natural toxin. Several
      functional monomers have been evaluated to maximize the interactions with the
      template molecule during the polymerization process. The polymer material
      prepared with 1-allylpiperazine (1-ALPP) as functional monomer, trimethyl
      trimethacrylate (TRIM) as cross-linker and acetonitrile as porogen (in a 1:4:20
      molar ratio) displayed superior binding capacities than any other of the MIPs
      tested. Selectivity of this material for ZON and structurally related and non
      related compounds has been evaluated using it as stationary phase in liquid
      chromatography. Our results demonstrate that the imprinted polymer shows
      significant affinity in the porogenic solvent for the template mimic (CDHB) as
      well as for the ZON and other related target metabolites in food samples,
      dramatically improving the performance of previously reported MIPs for ZON
      recognition. Therefore, MIPs can be an excellent alternative for clean-up and
      preconcentration of the mycotoxin in contaminated food samples.

PMID- 16595139
TI  - Determination of zonisamide by a coated monolithic column.
AB  - In this paper, a monolithic ODS-silica gel column dynamically coated with
      cetylpyridinium chloride (CPC) was used to demonstrate the high-speed and
      efficient separation of zonisamide (1,2-benzisoxazole-3-methanesulfonamide, ZNS),
      its raw material (1,2-benzisoxazole-3-methanecarbonic acid) and intermediate
      (sodium 1,2-benzisoxazole-3-methanesulfonate) in drugs. Using a 40 mmol/L sodium
      perchlorate solution (pH 7.0) containing 10% acetonitrile as eluent, the analytes
      were eluted with a sharp and symmetrical peak within 3.0 min, detected with UV
      detection at 210 nm. The column demonstrates excellent stability over time, and
      exhibits unusual selectivity for pharmaceutical analysis. Thus, by this developed
      method, zonisamide in drug samples can be determined rapidly with high recoveries
      and good selectivity.

PMID- 16595140
TI  - Form completion across a hemianopic boundary: behindsight?
AB  - Patients with homonymous hemianopia may report the completion of forms that
      overlap the vertical meridian of their field defects. While previous
      investigations of "hemianopic completion" have variously attributed to the
      disorder to inattention, residual vision or unstable fixation, we believe that
      our investigation has controlled for such potentially confounding factors. We
      report patient P.O.V. who experienced hemianopic completion in everyday life
      following a surgical lesion of his left occipital lobe. He showed normal spatial
      attention and normal spatial orienting: hemianopic completion can therefore occur
      in the absence of inattention. His completion was retinotopic and affected
      partial as well as complete forms: his hemianopic completion cannot be attributed
      to residual visual input or poor fixation. P.O.V.'s completion was also
      systematically affected by varying stimulus contrast and pattern masking. We
      argue that while other explanations may be appropriate for different cases,
      P.O.V.'s hemianopic completion reflects normal "constructive" visual processes
      and can be attributed to the unconstrained operation of visual routines that are
      normally involved in the perception of partially occluded forms. As such, this
      disorder has the potential to shed light on some of the most basic aspects of
      visual perception.

PMID- 16595141
TI  - Infection of human dendritic cells with recombinant vaccinia virus MVA reveals
      general persistence of viral early transcription but distinct maturation
      dependent cytopathogenicity.
AB  - Vector-infected dendritic cells (DC) are evaluated for antigen delivery in
      experimental therapy of cancer and infectious diseases. Here, we investigated
      infections of immature or mature, monocyte-derived human DC with recombinant
      vaccinia virus MVA producing human Her-2/neu, a candidate tumor-associated
      antigen. Assessment of the molecular virus life cycle in infected DC revealed a
      general arrest at the level of viral early gene expression. When monitoring the
      phenotype of MVA-infected DC, including expression of cell surface markers, we
      found immature cells readily undergoing apoptosis. Nevertheless, we detected
      significant populations of viable DC being characterized by high level Her-2/neu
      expression and unimpaired display of costimulatory molecules. While infected
      viable immature DC failed to undergo maturation despite cytokine treatment, both
      DC populations efficiently presented MVA-produced target antigen. These findings
      allow to better define the requirements for MVA-mediated antigen delivery to DC
      and help to derive optimized vectors for this advanced therapy option.

PMID- 16595142
TI  - Does sunlight have a beneficial influence on certain cancers?
AB  - Apperly [1941. The relation of solar radiation to cancer mortality in North
      America. Cancer Research 1, 191-195] first proposed that increased mortality from
      cancer in the north than in the south of the USA might be due to the south to
      north decrease in ambient solar radiation. This inverse association between
      ambient solar radiation and cancer mortality has been subsequently reported for
      cancers of the colon, breast, ovary and prostate. While the evidence that
      sunlight might be related to lower incidence or more favourable outcomes from
      cancer came initially from ecological studies, case-control and cohort studies
      have now shown a similar association of sun exposure with risks of colon, breast
      and prostate cancers in individuals, and other studies in individuals have found
      that serum and dietary vitamin D levels are associated with reduced risks of
      colorectal cancer and, less certainly, prostate cancer. Studies in individuals
      have recently also suggested an effect of sun exposure to reduce risk of non
      Hodgkin lymphoma and to increase survival after a diagnosis of melanoma. Data on
      variation in survival from cancer by season of diagnosis suggest that sun
      exposure may also improve outcome from cancers of the breast, colon and prostate
      and Hodgkin lymphoma.

PMID- 16595143
TI  - Effectiveness of information campaigns.
AB  - Skin cancer represents the most common type of cancer in the white population
      worldwide and the incidence has dramatically increased during the last decades.
      UV-radiation is believed to be the most important risk factor responsible for
      this trend. The prominent role of UV-radiation renders skin cancer most suitable
      for primary prevention, because the main risk factor can easily be avoided by
      sticking to simple rules for the behaviour in the sun or under artificial UV
      (e.g. sunbeds). Since UV-exposure cannot and should not be avoided totally
      especially due to the beneficial health effects of UV-irradiation like Vitamin
      D(3)-production, recommendations and information for the public should be as
      clear and as weighted as possible, through adequate messages, such as: "Love the
      sun and protect your skin". For that purpose the Association of Dermatological
      Prevention in Germany (ADP) developed the period of life programme (POLP) that
      defines certain age-specific target groups, with the aim to give well adapted
      prevention messages to the population during lifetime. Evaluation of primary
      prevention campaigns in Germany showed that due to continuous intervention
      programs during the last 16 years changes in the "sun-behaviour" of the
      population have been achieved leading to a reduced but sufficient exposure to
      solar UV-irradiation. This will then contribute to the aim of decreasing
      morbidity and mortality of skin cancer.

PMID- 16595145
TI  - Conservative treatment of reproductive and sexual function in young woman with
      squamous carcinoma of the vagina.
AB  - OBJECTIVE: Primary squamous carcinoma of the vagina in young woman is extremely
      rare. Conservative management of both sexual and reproductive function poses
      challenging problems to gynecologic oncologists. METHODS: Between January 2001
      and December 2004, four women under 40, nulliparous, with squamous cell carcinoma
      of the upper third of the vagina, at FIGO Stage I were submitted to conservative
      surgery of the reproductive/sexual function at our Institution. After written
      informed consent was obtained, conservative surgical treatment consisting of
      radical tumorectomy with pelvic lymphadenectomy, in three patients, and partial
      hemi-vaginectomy plus homolateral paracolpectomy/parametrectomy with pelvic
      lymphadenectomy, in the forth patient, was carried out. RESULTS: Mean operative
      time of conservative surgical treatment was 161 min. No intraoperative or
      postoperative complications were observed. In one patient, definitive pathologic
      examination revealed microscopic involvement of the paracolpium. Thus, after
      carrying out laparoscopic ovarian transposition, adjuvant radiotherapy (RT),
      consisting of pulsed-dose rate brachytherapy and external RT, was delivered in
      this woman. After a follow-up time of 51, 45, 21 and 9 months, respectively, all
      patients are regularly menstruating, sexually active and clinically free of
      disease. CONCLUSION: To our knowledge, this is the first report showing the
      feasibility and the efficacy of conservative surgery of reproductive and sexual
      function in young woman with vaginal carcinoma. A larger number of patients and a
      longer follow-up are needed to validate the safety of this approach.

PMID- 16595146
TI  - Expression of thrombospondin 1 (TSP 1) in patients with uterine smooth muscle
      tumors: an immunohistochemical study.
AB  - OBJECTIVE: Angiogenesis is an essential component for tumor development regulated
      by both proangiogenic and antiangiogenic factors. Thrombospondin 1 (TSP 1)
      suppresses angiogenesis by inhibiting endothelial cell proliferation and inducing
      endothelial cell apoptosis. The aim of this study was to compare the expression
      of TSP 1 in cases with leiomyoma, uterine smooth muscle tumor of uncertain
      malignant potential (STUMP) and leiomyosarcoma (LMS). Furthermore, we evaluated
      the prognostic relevance of TSP 1 in uterine LMS. METHODS: TSP 1 expression was
      investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients
      with leiomyoma, in 24 patients with STUMP and in 21 patients with LMS. Standard
      immunohistochemical techniques were used to study the expression of TSP 1 in 5
      mum-thick tumor sections. TSP 1 expression was correlated with survival using the
      Kaplan-Meier method and log-rank test for univariate analysis. RESULTS: TSP 1 was
      expressed in 77% of leiomyomas, in 13% of STUMP and in 24% of LMS. A
      statistically significant difference regarding the frequency of TSP 1 expression
      was observed between leiomyoma and LMS (P < 0.05) as well as between leiomyoma
      and STUMP (P < 0.05), but not between LMS and STUMP (P > 0.05). Furthermore, a
      statistically significant correlation between vascular space involvement and TSP
      1 expression was observed in patients with uterine LMS, with patients without
      vascular space involvement having more frequently TSP 1 positive tumors (P =
      0.04). No statistically significant correlation between TSP 1 and clinical stage,
      age and recurrence disease could be detected (P > 0.05). CONCLUSIONS: We found
      that TSP 1 was more frequently expressed in leiomyoma compared to STUMP and LMS.
      Additionally, the statistically significant negative correlation between vascular
      space involvement and TSP 1 expression in patients with uterine LMS shows that
      TSP 1 might work as a predictive factor in patients with LMS. Further clinical
      studies are necessary to prove our results and to clarify the role of TSP 1 in
      uterine smooth muscle tumors.

PMID- 16595148
TI  - Significance of early changes in the serum CA-125 antigen level on overall
      survival in advanced ovarian cancer.
AB  - OBJECTIVE: The relationship between survival and early changes in the serum level
      of the CA-125 antigen in patients with advanced ovarian cancer remains poorly
      defined. METHODS: To explore this issue, the serum CA-125 values from 101
      patients with advanced ovarian cancer who participated in a Southwest Oncology
      Group trial (SWOG 8412), which compared the systemic delivery of
      cisplatin/cyclophosphamide vs. carboplatin/cyclophosphamide (both delivered every
      28 days for 6 cycles) in suboptimal residual stage III and IV ovarian cancer,
      were evaluated. All patients in this analysis had CA-125 values available for at
      least 8 weeks following initiation of chemotherapy. Cox proportional hazards
      regression was used in multivariate analysis to determine the prognostic
      significance of the CA-125 concentration. RESULTS: While pretreatment CA-125
      values did not correlate with survival, the concentration of this tumor marker 8
      weeks after initiation of therapy was a powerful independent prognostic factor.
      The median survivals for patients (n = 51) with a CA-125 < 35 U/ml, vs. patients
      (n = 50) with a CA-125 > 35 U/ml, at this time point, were 26 months and 15
      months, respectively (P = 0.0001). Further, women with serum CA-125 values <50%
      of their pretreatment concentration at 8 weeks experienced a median survival of
      21 months, compared to only 10 months for individuals with tumor marker levels
      >50% of their baseline value (P = 0.0003). CONCLUSION: Reduction in the serum CA
      125 concentration over the initial two cycles of platinum-based chemotherapy is a
      powerful independent predictor of survival for patients with suboptimal stage III
      or IV ovarian cancer. Patients without significant declines in CA-125 after two
      cycles of platinum-based chemotherapy have a particularly poor prognosis.

PMID- 16595149
TI  - Incidence of ovarian cancer of grand multiparous women--a population-based study
      in Finland.
AB  - OBJECTIVES: Parity is known to induce protective effects on ovarian cancer. This
      study aimed to evaluate how far upon births the protection reaches, the effect of
      age at first birth, the interval between births in the whole population and the
      length of time from the first to the last birth and from the last birth to cancer
      among postmenopausal women. METHOD: The population-based cohort consisted of
      87,929 grand multiparous (GM) women, i.e. women with at least 5 deliveries.
      Standardised incidence ratios (SIRs) were calculated by dividing the number of
      observed cancer cases by the expected number based on the national incidence
      rates, both extracted from the population-based Finnish Cancer Registry.
      Conditional logistic regression for the case-control design nested in the GM
      cohort was used to estimate proportional hazards by different factors. RESULTS:
      The SIR for ovarian cancer among GM women was low (418 cases; SIR 0.64, 95%
      confidence interval 0.58-0.69). Further births over five did not give additional
      protection. The relative risk did not vary significantly by age at first birth or
      interval between the births in any histological subtype. CONCLUSION: The risk of
      ovarian cancer was low in all GM women no matter how many children and at which
      ages they had delivered or contracted cancer.

PMID- 16595147
TI  - Semi-quantitative fluorescent PCR analysis identifies PRKAA1 on chromosome 5 as a
      potential candidate cancer gene of cervical cancer.
AB  - OBJECTIVE: Comparative genomic hybridization has frequently detected
      amplification of chromosome 5p in cervical cancer, but candidate cancer genes
      within the region are rarely known. Therefore, we pursued to identify potential
      candidate gene related to cervical cancer development. METHODS: A series of 128
      cervical tumor samples were examined by semi-quantitative fluorescent
      differential PCR for copy number changes on three candidate genes (PRKAA1, CTNND2
      and POLS) mapped to chromosome 5p and one gene (ERBIN) mapped to chromosome
      5q12.3. The impact of gene copy number was later analyzed in relation to HPV
      infection, tumor stage or tumor radiosensitivity. RESULTS: DNA copy numbers of
      PRKAA1, CTNND2 and ERBIN were significantly different from normal controls (P <
      0.05). DNA copy number changes did not correlate with HPV infection, tumor stages
      or tumor radiosensitivity. Using RT-PCR, PRKAA1 mRNA expression in seven tumor
      samples with known 5p amplification was amplified from 3- to 15-fold. Over
      expression of PRKAA1 was further confirmed by immunohistochemical staining on 125
      paraffin-embedded cervical cancer tissues. The expression level in cervical tumor
      was significantly higher than that in normal epithelium (P < 0.001). CONCLUSIONS:
      PRKAA1 gene codes for the catalytic alpha 1 subunit of the AMP-activated protein
      kinase which is an important cellular metabolic stress regulator. It might assist
      tumor cells growth under stress. Thus, PRKAA1 may be one of the potential
      candidate genes for cervical carcinogenesis.

PMID- 16595150
TI  - Late influenza vaccination is associated with reduced effectiveness.
AB  - BACKGROUND: Extensive research has been carried out to quantify the efficacy and
      immunologic responses to influenza immunization, however, only little was
      reported on whether the timing of vaccine administration affects its
      effectiveness. The study aims were to compare post-immunization hospitalization
      and mortality rates among high-risk patients who were vaccinated against
      influenza in different periods of autumn. METHODS: Data for the current
      population-based historical prospective study were obtained from a large health
      organization in Israel insuring 1,600,000 members. Study population (n = 68,166)
      included high-risk patients aged 55 and above, who were immunized against
      influenza between October and November 2003. RESULTS: Although at baseline,
      individuals vaccinated in late November (12-25/11/2003) were significantly
      younger and had lower burden of illness compared to those vaccinated in early
      October (1-13/10/2003), they had higher hospitalization rates and longer hospital
      stay during the following winter (December to March). They also had an increased
      risk for all-cause mortality (RR = 1.78; 95%CI: 1.13-2.80). No such differences
      were observed during the following summer (April-August). CONCLUSIONS: In
      countries where influenza generally peaks between December and early March,
      vaccines administered after mid-November might be less beneficial.

PMID- 16595151
TI  - Effects of hCG as spermiation inducer on European eel semen quality.
AB  - Fish sperm quality has traditionally been estimated by subjective evaluation of
      motility and sperm concentration. Alternative methods for evaluation of sperm
      quality have been developed in the last decade and enable estimation of
      spermatozoa head morphometry, membrane integrity and mitochondrial function.
      Weekly injections of human chorionic gonadotropin (hCG) induced spermiation in
      farmed male European eels. The milt volume increased from the 5th to 12th weeks.
      Sperm concentration significantly increased from the 5th week, reaching the
      highest values at the 8th week, while best motility results were registered at
      the 9th week of treatment. Coinciding with these intervals, the percentage of
      dead spermatozoa determined with Hoechst staining showed a reduction in the 8th
      to 11th weeks of treatment, while the percentage of mitochondrial functionality
      determined by JC-1 staining did not show a similar pattern. The automatic sperm
      morphology analysis (ASMA) of the spermatozoa head length, width, area and
      perimeter showed a significant growth from the 5th to 8th weeks. However, the
      analysis of isolated descriptive parameters may be difficult to understand
      because there is a variability in these parameters for each week, making
      knowledge of the growth kinetic complex. The global size of the spermatozoa head
      was calculated by applying principal component analysis (PCA), because this
      method establishes new components that make the interpretation of results easier,
      allowing a whole interpretation of the changes in the cell morphology. PC1
      defines the global head size and shows a significant increase between the 5th and
      8th weeks of treatment, showing shorter changes until 12th week. PC2 shows a
      significant increase in the spermatozoa width from the 5th to 7th weeks.
      Considering the results of the variations in the principal components defining
      European eel spermatozoa morphometry, it may be concluded that hCG maturative
      treatment produced thick cells during the first weeks of spermiation, and
      subsequent samplings showed an increase in cell width and length. These changes
      in sperm morphometry coincide with the highest sperm quality assessed as sperm
      motility and concentration, as well as with the best results obtained in previous
      studies reporting the best sperm quality between weeks 8 and 10 of hCG treatment.
      These results support the use of ASMA and Hoechst staining techniques as
      alternative methods for the evaluation of fish sperm quality.

PMID- 16595152
TI  - The influence of surface coatings of dicalcium phosphate (DCPD) and growth and
      differentiation factor-5 (GDF-5) on the stability of titanium implants in vivo.
AB  - Mechanical stability of implants is usually tested by pull out or push out tests
      which destroy the interface between the implant and bone. Pull out tests do not
      ideally reflect the clinical situation. In contrast, applying submaximal load
      leads to more physiologic micro-displacement between implant and bone. The aim of
      this study was to evaluate a new non-destructive mechanical testing device on
      different modifications of titanium implants. In 18 rabbits we investigated the
      influence of a dicalcium phosphate (DCPD) coating, or of a growth and
      differentiation factor-5 (GDF-5) coating, or a combination of both on the
      stability of titanium implants. The stability of implant was assessed by a non
      destructive micro-measurement. In the same specimens the interface was
      investigated by micro-CT and histological evaluation. Surface modifications had a
      positive effect on the implant stability regarding displacement (p=0.001).
      Mechanical stability correlated with the quality of peri-implant tissue. Micro
      displacement correlated negatively with the bone formation around the implants in
      histomorphometric evaluation (p=0.02). Amount of peri-prosthetic soft tissue
      showed a positive correlation with micro-displacement (p=0.01). Our findings
      indicate the positive effect of DCPD and GDF-5 coatings on stability of titanium
      implants. Results demonstrate the non-destructive testing to be an effective
      method to evaluate mechanical stability of implants.

PMID- 16595153
TI  - Molecular organization of human Ficolin-2.
AB  - Human Ficolin-2 (L-Ficolin) is an oligomeric serum protein consisting of a
      collagen-like stalk and fibrinogen-like recognition domains. The protein binds to
      arrays of sugars present on different microorganisms, enhances phagocytosis and
      promotes activation of the lectin complement pathway. So far the detailed
      oligomeric structure and composition of human Ficolin-2 has not been determined.
      Recombinant human Ficolin-2 was expressed in Chinese hamster ovary cells and its
      structure and biological functions were investigated by gel filtration, sucrose
      density gradient ultracentrifugation, mass spectrometry and surface plasmon
      resonance spectroscopy. It was revealed that Ficolin-2 has a high molecular
      weight due to extensive disulfide bridge formation. It was able to bind to
      different ligands, interact with mannose-binding lectin associated serine
      proteases and activate the complement system. Mass values of 807 and 403 kDa were
      determined corresponding to a 24-mer and a 12-mer of 34.4 kDa polypeptides.
      However, the 24-mer was unstable and the 12-mer is likely the major functional
      form of the protein. Our results are consistent with the view that Ficolin-2 is
      built up by a mixture of stable homodimers and homotrimers. Based on our findings
      we propose a model in which disulfide bridges located in the N-terminal region of
      the polypeptides explain the oligomerization pattern of human Ficolin-2.

PMID- 16595154
TI  - Principles: when there should be no difference--how to fail to reject the null
      hypothesis.
AB  - It is common to perform experiments in which a 'success' is claimed when the null
      hypothesis is discarded. However, there is a category of experiment that has
      become important in which a success is when the null hypothesis is not rejected.
      Failing to discard the null hypothesis is different from proving it to be valid,
      a distinction that is particularly important in experiments in which any
      inadequacy of experimental design or implementation enhances the likelihood of a
      success. The appropriate analysis of such experiments tests for evidence of the
      validity of the null hypothesis rather than simply failing to find evidence
      against it.

PMID- 16595155
TI  - Bilirubin potentiates inhibitory synaptic transmission in lateral superior olive
      neurons of the rat.
AB  - Bilirubin is a well-known neurotoxin that can result in multiple neurologic
      deficits. Previous studies have suggested that bilirubin affects aspects of
      synaptic transmission; however the acute effects of bilirubin on synaptic
      transmission have not been examined in real-time. In this study, using whole-cell
      voltage-clamp recordings, we observed the effect of bilirubin on inhibitory
      postsynaptic currents (IPSC) in postnatal 13-15-day-old neurons dissociated from
      lateral superior olive nuclei (LSO), one of the brainstem auditory nucleus that
      are highly vulnerable to bilirubin. The results showed that 10(-5)M bilirubin
      increased the frequency of spontaneous IPSC without causing change in their
      amplitudes or in the response to bath applied glycine, suggesting a presynaptic
      locus for the action. In the presence of tetrodotoxin, the frequency of miniature
      IPSC was also potentiated by 10(-5)M bilirubin. The facilitation by bilirubin was
      concentration dependent and increased with an increase in exposure time.
      Bicuculline only partially reduced the action of bilirubin. The action of
      bilirubin was observed in extracellular Ca(2+)-free ([Ca(2+)](o) free) solution
      but was fully occluded by pretreatment with BAPTA-AM in [Ca(2+)](o) free
      solution. Thus, in LSO neurons, bilirubin facilitates inhibitory synaptic
      transmission, in a manner independent of voltage-activated Na(+) and Ca(2+)
      channels but dependent on presynaptic [Ca(2+)](i). The increase of inhibitory
      synaptic transmission in response to acute bilirubin is a novel effect of
      bilirubin on the central nervous system and may have implications for
      neurotoxicity and the impairment of auditory transduction seen in
      hyperbilirubinemia.

PMID- 16595156
TI  - Hourglass SiO2 coating increases the performance of planar patch-clamp.
AB  - Obtaining high-throughput electrophysiological recordings is an ongoing challenge
      in ion channel biophysics and drug discovery. One particular area of development
      is the replacement of glass pipettes with planar devices in order to increase
      throughput. However, successful patch-clamp recordings depend on a surface
      coating which ideally should promote and stabilize giga-seal formation. Here, we
      present data supporting the use of a structured SiO(2) coating to improve the
      ability of cells to form a "seal" with a planar patch-clamp substrate. The method
      is based on a correlation study taking into account structure and size of the
      pores, surface roughness and chip capacitance. The influence of these parameters
      on the quality of the seal was assessed. Plasma-enhanced chemical vapour
      deposition (PECVD) of SiO(2) led to an hourglass structure of the pore and a
      tighter seal than that offered by a flat, thermal SiO(2) surface. The performance
      of PECVD chips was validated by recording recombinant potassium channels, BK(Ca),
      expressed in stable HEK-293 cell lines and in inducible CHO cell lines and low
      conductance IRK1, and endogenous cationic currents from CHO cells. This
      multiparametric investigation led to the production of improved chips for planar
      patch-clamp applications which allow electrophysiological recordings from a wide
      range of cell lines.

PMID- 16595157
TI  - The current status of home and office blood pressure control among hypertensive
      patients with diabetes mellitus: the Japan Home Versus Office Blood Pressure
      Measurement Evaluation (J-HOME) study.
AB  - Although self-measured blood pressure (BP) at home (HBP) has become popular in
      clinical practice, little information is available regarding the proportion of
      diabetic patients with properly controlled HBP. We evaluated the status of HBP
      control in diabetic hypertensives. HBP control status was cross-sectionally
      evaluated among 3400 essential hypertensives taking antihypertensive treatment.
      Of these, 466 (14%) had diabetes. Physicians evaluated the subjects' HBP control
      as "poor", "fairly good", or "excellent" using a self-administered questionnaire.
      When the HBP threshold in diabetic patients was set tentatively at 130/80 mmHg or
      135/85 mmHg, HBP was properly controlled in 18% or 30% of diabetic patients,
      respectively. The same trend was observed in office BP. The average number of
      drugs prescribed for diabetic patients was 2.0 drugs. In the majority of diabetic
      patients with uncontrolled BP, the BP control status in two-thirds of those was
      evaluated as "excellent" or "fairly good" by their physicians. In Japan, HBP and
      office BP were not adequately controlled in most diabetic hypertensives. The main
      reason for this would appear to be a lack of intensive treatment and a lack of
      recognition by physicians that their patients' BP was insufficiently controlled.

PMID- 16595158
TI  - Oxidative stress inhibits IFN-alpha-induced antiviral gene expression by blocking
      the JAK-STAT pathway.
AB  - BACKGROUND/AIMS: Unresponsiveness to IFN-alpha is common in chronic hepatitis C.
      Since conditions associated with an increased oxidative stress (advanced age,
      steatosis, fibrosis, iron overload, and alcohol consumption) reduce the
      likelihood of response, we hypothesized that oxidative stress may affect the
      antiviral actions of IFN-alpha. METHODS: We examined in a human hepatocellular
      carcinoma cell line (Huh-7) the effect of hydrogen peroxide (H2O2), as a
      generator of oxidative stress, on the IFN-alpha signaling pathway. RESULTS:
      Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the
      IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. The reduced
      expression of these genes was associated to H2O2 -mediated suppression of the IFN
      alpha-induced assembly of signal transducer and activator of transcription (STAT)
      factors to specific promoter motifs on IFN-alpha-inducible genes. This was
      accomplished by preventing the IFN-alpha-induced tyrosine phosphorylation of STAT
      1 and STAT-2 through the inactivation of the upstream receptor associated
      tyrosine kinases, JAK-1 and Tyk-2. The suppression was fast, occurring within
      5mins of pretreatment with H2O2, and did not require protein synthesis.
      CONCLUSIONS: In conclusion, oxidative stress impairs IFN-alpha signaling and
      might cause resistance to the antiviral action of IFN-alpha in chronically HCV
      infected patients with high level of oxidative stress in the liver.

PMID- 16595159
TI  - Role of the kallikrein-kinin system in Ang-(1-7)-induced vasodilation in
      mesenteric arterioles of Wistar rats studied in vivo-in situ.
AB  - Angiotensin-(1-7) [Ang-(1-7)], exerts a variety of actions in the cardiovascular
      system, with an important effect being vasodilation. In this work, we
      investigated the relationship between the vasodilatory activity of Ang-(1-7) and
      the kallikrein-kinin system. Intravital microscopy was used to study the
      vasodilation caused by Ang-(1-7) in the mesenteric vascular bed of anesthetized
      Wistar rats. The topical application of Ang-(1-7) caused vasodilation of
      mesenteric arterioles that was reduced by A-779, JE 049 and peptidase inhibitors
      (aprotinin, SBTI, PKSI 527, E-64, PMSF). These results indicated that the
      vasodilation induced by Ang-(1-7) in the mesenteric arterioles of Wistar rats was
      heavily dependent on the activation of kallikrein and subsequent kinin formation.

PMID- 16595160
TI  - A TAP2 genotype associated with Alzheimer's disease in APOE4 carriers.
AB  - Sporadic Alzheimer's disease (AD) appears to be the consequence of the
      interaction between combinations of genes and environmental factors. Binding with
      the transporter associated with antigen processing (TAP) is thought to be the
      main way in which herpes simplex virus type 1 (HSV-1) evades immune surveillance.
      Several TAP gene polymorphisms were examined and a TAP2 SNP (rs241448) associated
      with AD found in two independent case-control samples, especially in carriers of
      the APOE4 allele. These findings are consistent with the hypothesis that human
      genetic variants facilitating the access of HSV-1 to the brain might result in
      susceptibility to AD.

PMID- 16595161
TI  - Metal ions induced heat shock protein response by elevating superoxide anion
      level in HeLa cells transformed by HSE-SEAP reporter gene.
AB  - The aim of this work is to define the relationship between heat shock protein
      (HSP) and reactive oxygen species (ROS) in the cells exposed to different
      concentrations of metal ions, and to evaluate a new method for tracing the
      dynamic levels of cellular reactive oxygen species using a HSE-SEAP reporter
      gene. The expression of heat shock protein was measured using a secreted alkaline
      phosphatase (SEAP) reporter gene transformed into HeLa cell strain, the levels of
      superoxide anion (O(2)(-)) and hydrogen peroxide (H(2)O(2)) were determined by
      NBT reduction assay and DCFH staining flow cytometry (FCM), respectively. The
      experimental results demonstrated that the expression of heat shock protein
      induced by metal ions was linearly related to the cellular superoxide anion level
      before cytotoxic effects were observed, but not related to the cellular hydrogen
      peroxide level. The experimental results suggested that metal ions might induce
      heat shock protein by elevating cellular superoxide anion level, and thus the
      expression of heat shock protein indicated by the HSE-SEAP reporter gene can be
      an effective model for monitoring the dynamic level of superoxide anion and early
      metal-induced oxidative stress/cytotoxicity.

PMID- 16595162
TI  - Clinico-pathological significance of RCAS1 expression in gliomas: a potential
      mechanism of tumor immune escape.
AB  - RCAS1, one of the tumor cell surface antigens, is strongly expressed in
      aggressive tumors. RCAS1 suppresses the in vitro growth of immune effector cells.
      We investigated the expression of RCAS1 in 57 gliomas using immunohistochemistry.
      Furthermore, we examined the association of the RCAS1 expression with the
      infiltration of tumor infiltrating lymphocyte (TIL). RCAS1 overexpression was
      significantly correlated with high histological grade and poor prognosis. Reduced
      infiltration and increased apoptosis of TILs was observed in RCAS1-positive
      regions. Apoptotsis of TILs appeared to be induced by RCAS1. RCAS1 expression in
      gliomas may play roles in tumor progression and tumor immune escape.

PMID- 16595163
TI  - Gene expression and association analysis of LIM (PDLIM5) in major depression.
AB  - LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and
      the N-type calcium channel alpha-1B subunit and modulates neuronal calcium
      signaling. Recently, the LIM mRNA expression in postmortem brains and
      immortalized lymphoblastoid cells from mood disorder patients was reported to be
      changed and seems to be involved in its pathophysiology. We hypothesized that the
      expression of the LIM mRNA in the native peripheral leukocytes may be a good
      candidate for the biological marker for mood disorders. Twenty patients with
      major depression and age- and sex-matched control subjects were included in this
      expression study. The LIM mRNA levels in the peripheral leukocytes from drug
      naive depressive patients were significantly lower than those from control
      subjects and increased significantly after 4-week paroxetine treatments, to
      almost the same level as controls'. Hamilton depressive scores (HAM-D) were
      improved about 50% after 4-week treatment but neither paroxetine concentrations
      nor the changes of HAM-D scores showed significant correlation with the change of
      the mRNA levels. Then, we genotyped three single nucleotide polymorphic markers
      of LIM gene, which were reported to be associated with bipolar disorder in
      patients with major depression and control subjects (n=130, each), but there were
      no associations between these SNPs and major depression. Our investigation
      indicates that the lower expression levels of LIM mRNA in the peripheral
      leukocytes are associated with the depressive state and that its recovery after
      treatment may be an adaptive change induced by the antidepressant.

PMID- 16595164
TI  - Normal distribution of presenilin-1 and nicastrin in skeletal muscle and the
      differential responses of these proteins after denervation.
AB  - Presenilin-1 and nicastrin, two components of gamma-secretase associated with
      Alzheimer's disease plaques, are present in the synapses of the brain and in
      various peripheral organs, including skeletal muscle. In the present study, we
      examined the expression pattern of presenilin-1 and nicastrin in normal and
      denervated hindlimb muscles of the rat. Using immunohistochemical approaches, we
      found that presenilin-1 and AChRalpha was co-localized at the neuromuscular
      junction in the normal skeletal muscles of rats. The immunoreactivities of both
      presenilin-1 and nicastrin were also observed at the sarcolemma of muscle fibers.
      We discovered that presenilin-1 mRNA and its protein are upregulated after
      denervation of the soleus and tibialis anterior muscles. Furthermore, clear co
      localization between presenilin-1 and DAPI, but not nicastrin, was noted in
      several myonuclei in the denervated muscles. We recognized a few fibers
      possessing both ubiquitin and presenilin-1 protein in the cytosol. The amount of
      presenilin-1 in the nucleus and membrane fraction was more abundantly expressed
      in the denervated muscle fibers. In contrast, no significant difference in the
      nicastrin protein level was observed between normal and denervated muscle fibers.
      These data suggest that enhanced presenilin-1 protein may play a role in the
      degeneration and regeneration of skeletal muscle.

PMID- 16595165
TI  - Memory functioning in polysubstance dependent women.
AB  - BACKGROUND: The vast majority of studies on polysubstance abuse or dependence
      have utilized male participants; therefore, the specific neuropsychological
      effects of polysubstance dependence in women are relatively unknown. The goal of
      the present study is to examine the effects of polysubstance dependence on
      women's verbal and visual memory ability. METHODS: Data were collected from 109
      women (46 controls and 63 polysubstance dependence women who were similar in
      ethnic identification, education, age, and verbal ability). A series of multiple
      regressions were run to test whether group membership significantly predicted
      performance on the Benton Visual Retention Test and the California Verbal
      Learning Test after controlling for important demographic characteristics.
      RESULTS: The primary results indicated that the polysubstance dependent women had
      significantly poorer verbal learning ability (ranging from p<.005 to .05) than
      the control group, while no differences were found in visual memory ability.
      Further, significant bivariate relationships were observed between frequency of
      alcohol and cocaine use and verbal learning, delayed recall, and recognition
      ability. CONCLUSIONS: The results confirm that polysubstance dependence is
      associated with deficient encoding of verbal information. In addition, past year
      frequent use of alcohol and cocaine was associated with more severe deficits in
      delayed recall and recognition ability among polysubstance dependent women at the
      bivariate level.

PMID- 16595166
TI  - Thiomers: preparation and in vitro evaluation of a mucoadhesive nanoparticulate
      drug delivery system.
AB  - It was the aim of this study to develop a mucoadhesive nanoparticulate delivery
      system. Nanoparticles were generated by in situ gellation of the thiomer chitosan
      4-thiobutylamidine (chitosan-TBA) with tripolyphosphate (TPP) followed by
      stabilization via the formation of inter- and intrachain disulfide bonds by
      oxidation with H(2)O(2) in various concentrations. Afterwards TPP was removed by
      exhaustive dialysis at pH 1-2. Incorporation of the model compound fluorescein
      diacetate (FDA) was achieved by incubation of this fluorescence marker, dissolved
      in acetonitrile, with aqueous particle suspensions for 1h at room temperature.
      Mucoadhesion studies were performed on porcine intestinal mucosa. Results showed
      that the preparation method described above leads to nanoparticles of a mean
      diameter of 268+/-15 nm and a FDA load of 2%. Due to the removal of the anionic
      crosslinker TPP, the zeta potential of the nanoparticles was raised from 4+/-1 up
      to 19+/-2 mV without loosing stability of the nanoparticles. The more H(2)O(2)
      was added to the particles, the more inter- and intrachain disulfide bonds were
      formed. The more thiol groups were oxidized within the particles, however, the
      lower was the improvement in mucoadhesive properties. Nevertheless, even when 91%
      of all thiol groups on the nanoparticles were oxidized, their mucoadhesive
      properties were still twice as high as the mucoadhesive properties of unmodified
      nanoparticles. Thiolated chitosan nanoparticles show a two-fold higher zeta
      potential (I), improved stability (II) and more than doubled mucoadhesive
      properties (III) than corresponding unmodified chitosan nanoparticles. Therefore,
      they seem to be advantageous over ionically crosslinked chitosan nanoparticles.

PMID- 16595167
TI  - Hepatic radiofrequency ablation using perfusion electrodes in a pig model: effect
      of the Pringle manoeuvre.
AB  - AIM: To assess the influence of the Pringle manoeuvre on volume and geometry of
      coagulations close to the portal vein using an impedance-controlled
      radiofrequency ablation system with perfusion electrodes. METHODS: Twelve pigs
      were randomly assigned to a control group (n = 6) and a group where the Pringle
      manoeuvre was applied during ablation (n = 6). One coagulation was made in each
      animal close to the portal vein. All animals were sacrificed 4 days after
      ablation, and the livers were removed for gross and histopathologic analysis.
      RESULTS: Effective coagulation volume in the Pringle group (10.8 +/- 5.0 cm(3))
      was significantly increased (p = 0.03) compared to the control group (4.1 +/- 4.1
      cm(3)). The efficacy ratio, defined as the effective coagulation volume divided
      by the coagulation volume, was not significantly different in the Pringle group
      (0.47 +/- 0.27) compared to the control group (0.33 +/- 0.22). The geometrical
      centre of the effective coagulation volume did not correspond to the position of
      the ablation electrode. Thermal damage of the gallbladder was found in three
      animals, all belonging to the Pringle group. CONCLUSIONS: The Pringle manoeuvre
      was associated with increased effective coagulation volume, but did not
      significantly influence the predictability of coagulation volume or geometry.

PMID- 16595168
TI  - Sentinel lymph node biopsy in multicentric breast cancer. The experience of the
      European Institute of Oncology.
AB  - AIM: To present our experience with sentinel lymph node biopsy (SLNB) performed
      in patients with multicentric breast cancer. METHODS: Between May 2001 and May
      2004, 42 patients with multicentric breast cancer and a clinically negative
      axilla underwent lymphatic mapping either by a single subareolar (n = 25) or a
      double peritumoral/subdermal injection (n = 17) of 99Tc-HSA nanocolloids. The
      sentinel lymph node (SLN) was evaluated by intraoperative frozen section and
      axillary dissection was performed only in case of positive SLN. RESULTS: Mean age
      was 49 years (range 25-78). Mean number of SLNs identified by lymphoscintigraphy
      was 1.36 (range 1-5) and mean number of SLNs removed at surgery was 1.55 (range 1
      5), with an identification rate of 100%. The mean number of hot spots identified
      by lymphoscintigraphy was similar in patients who underwent single or double
      injections (1.36 and 1.35, respectively). In 21 of 42 patients the SLN was
      positive, and in seven of these 21 patients the SLN was the only positive node.
      After a median follow-up of 24 months no overt axillary metastases occurred in
      patients with negative SLN. CONCLUSIONS: The number of SLNs is not dependent on
      the number and site of injections. SLNB is our standard procedure for nodal
      staging in patients with multicentric breast cancer and a clinically negative
      axilla.

PMID- 16595169
TI  - Early transposable element insertion in intron 9 of the Hsf4 gene results in
      autosomal recessive cataracts in lop11 and ldis1 mice.
AB  - Lens opacity 11 (lop11) is an autosomal recessive mouse cataract mutation that
      arose spontaneously in the RIIIS/J strain. At 3 weeks of age mice exhibit total
      cataracts with vacuoles. The lop11 locus was mapped to mouse chromosome 8.
      Analysis of the mouse genome for the lop11 critical region identified Hsf4 as a
      candidate gene. Molecular evaluation of Hsf4 revealed an early transposable
      element (ETn) in intron 9 inserted 61 bp upstream of the intron/exon junction.
      The same mutation was also identified in a previously mapped cataract mutant,
      ldis1. The ETn insertion altered splicing and expression of the Hsf4 gene,
      resulting in the truncated Hsf4 protein. In humans, mutations in HSF4 have been
      associated with both autosomal dominant and recessive cataracts. The lop11 mouse
      is an excellent resource for evaluating the role of Hsf4 in transparency of the
      lens.

PMID- 16595170
TI  - Functional consequences of naturally occurring DRY motif variants in the
      mammalian chemoattractant receptor GPR33.
AB  - Most members of the large family of rhodopsin-like G-protein-coupled receptors
      possess an evolutionarily conserved Asp-Arg-Tyr (DRY) motif in the C-terminal
      region of the third transmembrane domain. Mutations of residues within this motif
      usually abolish receptor function and, when they occur naturally, can even cause
      human diseases. By analyzing over 100 mammalian orthologs of the chemoattractant
      receptor GPR33 we identified several polymorphic and fixed sequence variations
      within the DRY motif. Unexpectedly, the naturally occurring mutation of Arg(3.50)
      to His in mouse GPR33 showed no difference from the wild-type receptor in several
      functional tests. Sequence analysis of GPR33 from Asian house mice revealed the
      polymorphic existence of Arg(3.50) and His(3.50) alleles in wild-trapped
      populations, further supporting the functional equivalence of both allelic
      variants. In contrast, the Arg(3.50) to Gly mutation found in hamster GPR33
      inactivates the receptor and may have contributed to pseudogenization of this
      gene in this species. Functional data with GPR33 variants indicate different
      receptor- and context-specific consequences of DRY mutations. Our study also
      reveals GPR33 as a new example illustrating missense mutations as a first step in
      the pseudogenization process.

PMID- 16595171
TI  - A BAC clone-based physical map of ovine major histocompatibility complex.
AB  - An ovine bacterial artificial chromosome (BAC) library containing 190,000 BAC
      clones was constructed and subsequently screened to construct a BAC-based
      physical map for the ovine major histocompatibility complex (MHC). Two hundred
      thirty-three BAC clones were selected by 84 overgo probes designed on human,
      mouse, and swine MHC sequence homologies. Ninety-four clones were ordered by DNA
      fingerprinting to form contigs I, II, and III that correspond to ovine MHC class
      I-class III, class IIa, and class IIb. The minimum tiling paths of contigs I, II,
      and III are 15, 4, and 4 BAC clones, spanning approximately 1900, 400, and 300
      kb, respectively. The order and orientation of most BAC clones in each contig
      were confirmed by BAC-end sequencing. An open gap exists between class IIa and
      class III. This work helps to provide a foundation for detailed study of ovine
      MHC genes and of evolution of MHCs in mammals.

PMID- 16595172
TI  - Mirror neurons and imitation: a computationally guided review.
AB  - Neurophysiology reveals the properties of individual mirror neurons in the
      macaque while brain imaging reveals the presence of 'mirror systems' (not
      individual neurons) in the human. Current conceptual models attribute high level
      functions such as action understanding, imitation, and language to mirror
      neurons. However, only the first of these three functions is well-developed in
      monkeys. We thus distinguish current opinions (conceptual models) on mirror
      neuron function from more detailed computational models. We assess the strengths
      and weaknesses of current computational models in addressing the data and
      speculations on mirror neurons (macaque) and mirror systems (human). In
      particular, our mirror neuron system (MNS), mental state inference (MSI) and
      modular selection and identification for control (MOSAIC) models are analyzed in
      more detail. Conceptual models often overlook the computational requirements for
      posited functions, while too many computational models adopt the erroneous
      hypothesis that mirror neurons are interchangeable with imitation ability. Our
      meta-analysis underlines the gap between conceptual and computational models and
      points out the research effort required from both sides to reduce this gap.

PMID- 16595173
TI  - Perceiving the unusual: temporal properties of hierarchical motor representations
      for action perception.
AB  - Recent computational approaches to action imitation have advocated the use of
      hierarchical representations in the perception and imitation of demonstrated
      actions. Hierarchical representations present several advantages, with the main
      one being their ability to process information at multiple levels of detail.
      However, the nature of the hierarchies in these approaches has remained
      relatively unsophisticated, and their relation with biological evidence has not
      been investigated in detail, in particular with respect to the timing of
      movements. Following recent neuroscience work on the modulation of the premotor
      mirror neuron activity during the observation of unpredictable grasping
      movements, we present here an implementation of our HAMMER architecture using the
      minimum variance model for implementing reaching and grasping movements that have
      biologically plausible trajectories. Subsequently, we evaluate the performance of
      our model in matching the temporal dynamics of the modulation of cortical
      excitability during the passive observation of normal and unpredictable movements
      of human demonstrators.

PMID- 16595174
TI  - Development of an enrichment medium to detect Dekkera/Brettanomyces bruxellensis,
      a spoilage wine yeast, on the surface of grape berries.
AB  - Brettanomyces bruxellensis spoilage is a serious problem for the wine industry.
      Mainly, by producing 4-ethylphenol and 4-ethylguaiacol, it confers off-odors to
      the wine and changes its aromatic quality. The presence of B. bruxellensis cells
      on the berry was speculated but it had never been clearly demonstrated. On grape
      berries, the microbial ecosystem is highly diverse and the population of B.
      bruxellensis can be very small. The aim of our study was to reveal and confirm
      the presence of B. bruxellensis on the surface of grape berries. We developed an
      enrichment medium for B. bruxellensis in order to overcome the detection limit of
      the molecular methods (species-specific PCR, ITS-RFLP PCR, PCR-DGGE). This
      medium, named EBB medium, made it possible to detect B. bruxellensis after 10
      days of culture. For the first time, the presence of B. bruxellensis has been
      clearly established in several vineyards and at different stages of the grape
      development after the veraison. This work led to the conclusion that the grape
      berry is the primary source of B. bruxellensis. Grape growers and winemakers
      should take these results into account when deciding on the treatment to apply in
      the vineyards and the must. With the information provided here, B. bruxellensis
      prevention could start in the vineyard.

PMID- 16595175
TI  - IQGAP1 in cellular signaling: bridging the GAP.
AB  - IQGAP1 was identified in 1994 as a widely expressed IQ domain-containing protein
      with a region containing sequence similarity to the Ras GTPase-activating
      proteins. IQGAP1 has roles in many different aspects of cell physiology and
      interacts with numerous proteins. It modulates the actin cytoskeleton through
      Rac1 and Cdc42, and cell-cell adhesion through E-cadherin and beta-catenin. It
      also regulates the mitogen activated protein kinase pathway, which influences
      cell proliferation and differentiation. Evidence suggests that IQGAP1 is a
      scaffold protein that links components of signaling cascades. Here, we evaluate
      recent data that identify the participation of IQGAP1 in signaling networks and
      we illustrate how this influences diverse cellular functions. These findings
      suggest that IQGAP1 integrates signaling pathways and coordinates several
      fundamental cellular activities.

PMID- 16595176
TI  - Apoptosomes: protease activation platforms to die from.
AB  - Apoptosis is orchestrated by members of the caspase family of cysteine proteases
      that exist as latent pro-enzymes in healthy cells. Caspase-activating platforms,
      called apoptosomes, initiate caspase activation in metazoans as diverse as
      nematodes and mammals. Several recent studies have generated new insights into
      the composition and assembly mechanisms of worm, fly and human apoptosomes.

PMID- 16595177
TI  - Quality assurance in congenital heart surgery.
AB  - OBJECTIVE: The aim of this study was to develop a graphical method of risk
      stratified outcome analysis in paediatric cardiac surgery to provide a means of
      continuous, prospective performance monitoring and allow real-time detection of
      change in outcomes. METHODS: Risk-adjusted survival following open-heart surgery
      was prospectively measured over a 15-month period (n=460). Outcomes were charted
      using variable life-adjusted display (VLAD) charts, which indicate the cumulative
      difference in observed minus expected survival against the cumulative number of
      cases performed. Risk stratification was based on RACHS-1 (risk adjustment in
      congenital heart surgery) risk category and age at surgery, using our previously
      published risk model. The probability of deviation in performance from the
      expected baseline level was determined using a mathematical model. RESULTS: By
      the end of the series, observed survival (443/460=96.3%) exceeded that predicted
      by the risk model (434.5/460=94.5%), equivalent to a one-third reduction in
      expected mortality. Mathematical modelling indicated a 1-5% likelihood that this
      difference would have occurred by random variation alone, suggesting the outcomes
      represented genuine improvement. CONCLUSIONS: VLAD charts provide an effective,
      easily visualised display of surgical performance and can be applied to
      paediatric cardiac surgery. Early detection of change, whether improvement or
      deterioration, is important for ongoing quality assurance within a cardiac
      surgery programme.

PMID- 16595178
TI  - Mining the oocyte transcriptome.
AB  - Mammalian folliculogenesis and oocyte physiology are complex and not fully
      understood. However, major advances over the past 15 years in our ability to
      create and study in vivo models have improved our understanding of these
      essential physiological processes. More recently, the availability of vast arrays
      of DNA sequence information in the forms of "complete" genomes, expressed
      sequence tag libraries and microarray data from reproductive tissues have
      stimulated the discovery of new information through genome scanning, prediction
      programs and in silico screening techniques. These technological improvements
      will help to expand our understanding of folliculogenesis and oocyte physiology
      and improve human reproductive health.

PMID- 16595179
TI  - GRKs and beta-arrestins: roles in receptor silencing, trafficking and signaling.
AB  - Stimulation of cell-surface seven-transmembrane receptors (7TMRs) elicits
      biological responses to a wide range of extracellular signals, including many
      hormones. Classically, heterotrimeric GTP-binding proteins (G proteins) are
      recruited to the activated conformation of 7TMRs. Only two other families of
      protein have this remarkable characteristic: G-protein-coupled receptor kinases
      and beta-arrestins. These two protein families have long been known to have a
      central and coordinated role in the "desensitization" of G protein activation by
      7TMRs. In addition, G-protein-coupled receptor kinases and beta-arrestins are
      involved in an increasing number of interactions with non-receptor proteins,
      broadening the variety of their cellular functions. These newly appreciated
      attributes of these two families of protein highlight their unique ability to
      coordinate the various aspects of 7TMR functions.

PMID- 16595180
TI  - Interaction between Snapin and G-CSF receptor.
AB  - Granulocyte colony-stimulating factor (G-CSF) is the major cytokine involved in
      the control of neutrophil development. G-CSF activates the special receptor, the
      G-CSF receptor (GCSF-R), which subsequently triggers multiple signaling events.
      To obtain more interactive molecules with GCSF-R and to further understand the
      cellular signaling mechanism of GCSF-R, yeast two-hybrid system was used to
      screen a mouse liver library. Here, the interaction of GCSF-R and Snapin was
      found by yeast two-hybrid experiment, and the interaction of the two proteins was
      further confirmed by GST pull-down experiment, mammalian two-hybrid experiment
      and co-immunoprecipitation study. Moreover, the immuno-fluorescence assay was
      shown that the two proteins of GCSF-R with Snapin were co-localized in the
      cytoplasm and plasma membrane. The region of C-terminal GCSF-R between box2 and
      box3, including the residue Tyr703, was responsible for the interaction with
      Snapin. These data suggested that Snapin is a new interactive protein of GCSF-R.

PMID- 16595181
TI  - The fate of target visceral vessels after fenestrated endovascular aortic repair-
      general considerations and mid-term results.
AB  - OBJECTIVE: To carry out a retrospective analysis of the short and mid-term target
      vessels (TV) patency following fenestrated endovascular aortic repair (f-EVAR) of
      abdominal aneurysm (AAA). PATIENTS AND METHODS: Seventeen f-EVAR patients were
      analysed. The Zenith (Cook) fenestrated graft was used in all cases. Bare renal
      stents were used where good apposition existed between the stent graft and the
      aortic wall, and covered stents were chosen when this apposition appeared
      deficient. RESULTS: A total of 35 TV were treated: twenty with small fenestration
      and 15 with a scallop. Procedural technical success was achieved in 16 out of 17
      patients. All TV were perfused at the completion angiography. Access to TV
      through small fenestrations was achieved in 18 out of 20 vessels. After a mean
      follow-up of 20.5 months no type I endoleaks were detected. No late complications
      were observed in any of the stented TV. One patient with perioperative bilateral
      renal artery occlusion remains on haemodialysis. One non-target renal artery,
      opposite a scallop was unintentionally covered. One kidney, initially perfused
      via a un-stented scallop fenestration, was atrophied 14 months post surgery. One
      patient died from heart failure. CONCLUSIONS: f-EVAR is a valid and safe
      treatment option. Our series and the world literature demonstrates a >90% TV
      preservation rate. Long-term intensive surveillance is required.

PMID- 16595183
TI  - Neuro-Behcet disease presenting as secondary pseudotumor syndrome: case report.
AB  - Behcet's disease is a multisystemic, recurrent, inflammatory disorder, which has
      a three-symptom complex comprising uveitis, oral aphtae and genital ulcerations.
      It is rare in childhood. The prevalence of neurologic involvement in BD is range
      of 10-49%, and shows a wide spectrum from isolated headache to subacute
      encephalopathy and severe psychosis. We report a 12-year-old Behcet's disease
      patient with secondary pseudotumor syndrome due to cerebral vein thrombosis and
      aim to review the literature.

PMID- 16595182
TI  - Cloning and characterization of Plasmodium falciparum cysteine protease,
      falcipain-2B.
AB  - The gene for malaria parasite cysteine protease falcipain-2B has been isolated
      from the Plasmodium falciparum genomic DNA. Falcipain-2B gene is located adjacent
      to the falcipain-2A gene on chromosome 11, and the two enzymes show extensive
      sequence identity at the amino acid level. Using reverse transcribed polymerase
      chain reaction (RT-PCR), the transcript of falcipain-2B was detected at the
      trophozoite stage of P. falciparum in human erythrocytes. Recombinant falcipain
      2B protein expressed in bacteria exhibits protease activity as established by the
      cleavage of fluorescent peptide substrate as well as in-gel gelatin zymography.
      Importantly, the recombinant falcipain-2B cleaved host ankyrin but not protein
      4.1 as assessed by the erythrocyte inside-out-vesicle assay in vitro.
      Notwithstanding its predicted hemoglobinase function, the P. falciparum falcipain
      2B may contribute and orchestrate selective proteolytic events during the exit of
      malaria parasite from human red blood cells.

PMID- 16595184
TI  - Congenital Horner's syndrome associated with cervical neuroblastoma.
AB  - A 3-month-old girl was presented with a right-sided neck mass present since birth
      and accompanied by homolateral miosis, ptosis and enophthalmos (Horner's
      syndrome). Diagnostic work-up revealed an underlying cervical neuroblastoma.
      Although the association of Horner's syndrome with acquired neuroblastoma is well
      known and of value in early diagnosing of such a tumor, it can also be a
      presenting or accompanying sign in rare cases of congenital neuroblastoma.

PMID- 16595185
TI  - Hydrogen peroxide cleavage of the prion protein generates a fragment able to
      initiate polymerisation of full length prion protein.
AB  - The prion protein is central to the disease pathogenesis of a variety of
      neurodegenerative diseases such as CJD. The protein is only able to initiate the
      disease process following post-translational modification. The main
      characteristic of this change is the ability of this altered isoform to
      polymerise. We wish to determine if altered cleavage of the protein could
      generate a protein fragment able to initiate polymerisation. During normal
      metabolic breakdown the protein is initially cleaved at a single site at around
      amino acid residue 111/112 in the mouse sequence. A second site before amino acid
      residue 90 has been postulated as an alternative cleavage point. We have provided
      evidence that hydrogen peroxide as low as 50 microM in the presence of copper,
      iron or manganese (but not nickel, magnesium or zinc) can cleave the recombinant
      protein near this site and requires a GXXH motif in the protein sequence. This
      reaction results in the production of 6 and 19 kDa fragments of the protein. This
      cleavage pattern occurs in prion proteins from different species (mouse, chicken
      and turtle) and is enhanced by modification of the octameric repeat region. The
      19 kDa fragment produced by this reaction is protease sensitive. This fragment in
      a pure form caused the polymerisation of wild-type prion protein by a seeding
      mechanism. Therefore our results provide a possible mechanism by which altered
      cleavage of the prion protein could result in the kind of protein polymerisation
      associated with prion diseases.

PMID- 16595186
TI  - A module for syntactic processing in music?

PMID- 16595187
TI  - Green leaf volatiles: hydroperoxide lyase pathway of oxylipin metabolism.
AB  - Green leaf volatiles (GLVs) are C(6) aldehydes, alcohols, and their esters formed
      through the hydroperoxide lyase pathway of oxylipin metabolism. Plants start to
      form GLVs after disruption of their tissues and after suffering biotic or abiotic
      stresses. GLV formation is thought to be regulated at the step of lipid
      hydrolysis, which provides free fatty acids to the pathway. Recently, studies
      dissecting the physiological significance of GLVs in plants have emerged, and it
      has been postulated that GLVs are important molecules both for signaling within
      and between plants and for allowing plants and other organisms surrounding them
      to recognize or compete with each other.

PMID- 16595188
TI  - Protective effects of resveratrol against acetaminophen-induced toxicity in mice.
AB  - This investigation elucidates the role of free radicals in acetaminophen (AA)
      induced toxicity and the possible protection by resveratrol (RVT). BALB-c mice
      were injected with a single dose of 900mg/kg AA to induce toxicity, while RVT
      administred in a dose of 30mg/kg i.p. following AA. Mice were sacrificed 4h after
      AA injection to determine serum ALT, AST and tumor necrosis factor-alpha (TNF
      alpha) levels in blood, and glutathione (GSH), malondialdehyde (MDA) levels,
      myeloperoxidase (MPO) activity and collagen contents in liver tissues. Formation
      of reactive oxygen species in hepatic tissue samples was monitored by using
      chemiluminescence (CL) technique with luminol and lucigenin probe. ALT, AST
      levels and TNF-alpha were increased significantly after AA treatment, and reduced
      with RVT. AA caused a significant decrease in GSH levels while MDA levels and MPO
      activity were increased in liver tissues. On the other hand when RVT administered
      following AA, depletion of GSH and accumulation of MDA and neutrophil
      infiltration were reversed back to control. Furthermore increased luminol and
      lucigenin CL levels in the AA group reduced by RVT treatment. Our results
      implicate that AA causes oxidative damage in hepatic tissues and RVT, by its
      potent antioxidant effects protects the liver tissue. These data suggest that RVT
      may be of therapeutic use in preventing hepatic oxidative injury due to AA
      toxicity.

PMID- 16595189
TI  - Arm function after stroke: neurophysiological correlates and recovery mechanisms
      assessed by transcranial magnetic stimulation.
AB  - Transcranial Magnetic Stimulation has been used for over 20 years to investigate
      recovery of motor function in stroke patients. In particular, it has been used to
      quantify the extent of damage to the corticospinal output, reorganisation of the
      cortical representation of the affected body parts and excitability of
      intracortical and cortico-cortical circuitries in both hemispheres. In this
      review, we provide a detailed account of most of the published data with
      particular reference to methodological issues that affect their interpretation.

PMID- 16595190
TI  - Harnessing the potential of myogenic satellite cells.
AB  - Adult skeletal muscle has remarkable regenerative potential, which is mainly
      attributable to a small population of undifferentiated skeletal muscle precursors
      called satellite cells. These cells reside underneath the basal lamina of
      skeletal myofibers and can be activated to proliferate, differentiate and fuse to
      form new muscle tissue. Satellite cells have long been considered promising
      mediators of therapeutic muscle regeneration. However, in practice, the
      regenerative function of such cells, which in many cases have been derived or
      expanded by ex vivo cultures, can be surprisingly low. A recent study from
      Montarras and colleagues has provided new insights into the requirements for
      efficient muscle engraftment from purified muscle satellite cells, suggesting
      possible strategies to enhance their therapeutic potential.

PMID- 16595191
TI  - Adventitious mutations in clinical grade vectors: an issue to consider?

PMID- 16595193
TI  - Responses of terrestrial insects to hypoxia or hyperoxia.
AB  - Oxygen is critically important for catabolic ATP generation but is also a
      dangerous source of reactive oxygen species. Insects respond to short-term
      exposure to hypoxia or hyperoxia with compensatory changes in spiracular opening
      and ventilation that reduce variation in internal Po2. Below critical Po2 values
      (Pc), nitric oxide and hypoxia inducible factor (HIF)-mediated pathways induce
      long-term responses such as compensatory tracheal growth, suppressed development,
      and acclimation of ventilation. Pc values are strongly affected by activity and
      ontogeny, due to changes in the ratio of tracheal conductance to metabolic rate.
      Although growth rates and development are suppressed by significant hypoxia in
      all species studied to date, adult body size is only affected in some species.
      Severe hyperoxia causes major oxidative stress and reduces survival, while
      moderate hyperoxia increases development times and body sizes in some species by
      unknown mechanisms.

PMID- 16595192
TI  - Rad33, a new factor involved in nucleotide excision repair in Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae the Rad4-Rad23 complex is involved in initial damage
      recognition and responsible for recruiting the other NER proteins to the site of
      the lesion. The Rad4-Rad23 complex is essential for both NER subpathways,
      Transcription Coupled Repair (TCR) and Global Genome Repair (GGR). Previously, we
      reported on the role of the Rad4 homologue YDR314C in NER. YDR314C is essential
      for preferential repair of the transcribed strand in RNA pol I transcribed rDNA.
      In large scale interaction studies it was shown that YDR314C physically interacts
      with a small protein encoded by the ORF YML011C. In the present study we show
      that YML011C is involved in NER and we propose to designate the YML011C ORF
      RAD33. Cells deleted for RAD33 display intermediate UV sensitivity that is
      epistatic with NER. Strand specific repair analysis shows that GGR in RNA pol II
      transcribed regions is completely defective in rad33 mutants whereas TCR is still
      active, albeit much less efficient. In RNA pol I transcribed rDNA both GGR and
      TCR are fully dependent on Rad33. We show that in both rad23 and rad33 cells Rad4
      and YDR314C protein levels are significantly reduced. The homology of YDR314C to
      Rad4, together with the similar relation of both proteins to Rad33 prompted us to
      propose RAD34 as name for the YDR314C gene. Although the rad23rad33 double mutant
      is considerably more UV sensitive than a rad23 or rad33 single mutant, deletion
      of RAD33 in a rad23 background does not lead to a further reduction of Rad4 or
      Rad34 protein levels. This suggests that the role of Rad33 is not solely the
      stabilization of Rad4 and Rad34 but that Rad33 has an additional role in NER.

PMID- 16595194
TI  - Development and validation of a RP-HPLC method for quantification of isoflavone
      aglycones in hydrolyzed soy dry extracts.
AB  - Isoflavones are widely used as an alternative treatment to hormone replacement
      therapy and also for prevention of several chronic diseases, including cancers.
      Genistein, daidzein and glycitein are the most abundant isoflavone aglycones
      found in soy extracts, where they also occur as glycosides. This paper describes
      the development and validation of an isocratic reversed-phase HPLC (RP-HPLC)
      method for the analysis of isoflavone aglycones, released after acid hydrolysis
      of soy dry extracts, used as pharmaceutical raw material. The quantification was
      carried out in a C(18) endcapped column, using a mobile phase composed of 0.1%
      acetic acid and methanol (52:48), at a flow rate of 1.0 ml/min and diode array
      detection (DAD) at 254 nm. The method showed to be linear (r(2)>0.99), precise
      (R.S.D.<2%), accurate (recovery of 98.88% for daidzein and 98.12% for genistein),
      robust and specific.

PMID- 16595195
TI  - Tandem purification of two HDL-associated partner proteins in human plasma,
      paraoxonase (PON1) and phosphate binding protein (HPBP) using hydroxyapatite
      chromatography.
AB  - Human plasma paraoxonase (PON1) is calcium-dependent enzyme that hydrolyses
      esters, including organophosphates and lactones, and exhibits anti-atherogenic
      properties. Human phosphate binding protein (HPBP) was discovered as contaminant
      during crystallization trials of PON1. This observation and uncertainties for the
      real activities of PON1 led us to re-evaluate the purity of PON1 preparations. We
      developed a hydroxyapatite chromatography for the separation of both HDL
      associated proteins. We confirmed that: (1) HPBP is strongly associated to PON1
      in HDL, and generally both proteins are co-purified; (2) standard purification
      protocols of PON1 lead to impure enzyme; (3) hydroxyapatite chromatography allows
      the simultaneous purification of PON1 and HPBP.

PMID- 16595196
TI  - Doxorubicin coupled to lactosaminated albumin: Effects on rats with liver
      fibrosis and cirrhosis.
AB  - BACKGROUND: The conjugate of doxorubicin with lactosaminated human albumin has
      the potential of increasing the doxorubicin efficacy in the treatment of
      hepatocellular carcinomas expressing the asialoglycoprotein receptor. However,
      coupled doxorubicin also accumulates in the liver, which might damage
      hepatocytes. AIMS: To verify whether coupled doxorubicin impairs liver function
      in rats with liver fibrosis and cirrhosis. METHODS: Coupled doxorubicin was
      administered using the same schedule which exerted an antineoplastic effect on
      rat hepatocellular carcinomas (4-weekly injections of doxorubicin at 1 microg/g).
      Liver fibrosis/cirrhosis was produced by carbon tetrachloride (CCl4) poisoning.
      Liver samples were studied histologically. Serum parameters of liver function and
      viability were determined. RESULTS: In normal rats, administration of coupled
      doxorubicin neither caused microscopic changes of hepatocytes nor modified serum
      liver parameters. In rats with fibrosis/cirrhosis, although a selective
      doxorubicin accumulation within the liver followed coupled doxorubicin
      administration, the drug did not have a detrimental effect on the histology of
      the liver and, among serum liver tests, only alanine aminotransferase and
      aspartate aminotransferase levels were moderately modified. CONCLUSIONS: Coupled
      doxorubicin can be administered to rats with liver fibrosis/cirrhosis without
      inducing a severe liver damage. If further studies will confirm the efficacy and
      safety of this compound, coupled doxorubicin therapy may open a new perspective
      in the treatment of hepatocellular carcinoma.

PMID- 16595197
TI  - A new era in ovulation induction.
AB  - OBJECTIVE: To evaluate the efficacy of aromatase inhibitors in ovulation
      induction, superovulation, and IVF. DESIGN: A literature search was conducted
      with the key words "aromatase inhibitor," "letrozole," "anastrazole," "ovulation
      induction," "ovulation," and "superovulation" in MEDLINE, EMBASE, and the
      Cochrane Database of systematic reviews. RESULT(S): Ovulation induction with
      letrozole is associated with an ovulation rate of 70%-84% and a pregnancy rate of
      20%-27% per cycle. In one study, ovulation and pregnancy rates with letrozole
      seemed to be higher than those of anastrazole. In superovulation, letrozole is
      associated with few developing follicles and thick endometrium. The use of
      letrozole for superovulation is associated with a pregnancy rate higher than with
      the use of clomiphene citrate (CC) (16.7% vs. 5.6%). The addition of letrozole to
      FSH treatment leads to a decreased FSH requirement. The pregnancy rate for
      treatment with letrozole and FSH was similar to that for FSH alone.
      CONCLUSION(S): Aromatase inhibitors are as effective as or superior to CC in
      ovulation induction and in superovulation. Unlike CC, they do not carry an
      antiestrogenic effect on the endometrium. Given the advantages of aromatase
      inhibitors, they can be used to replace CC as ovulation-inducing drugs. Their
      role in IVF remains to be determined.

PMID- 16595198
TI  - Human immunodeficiency virus infection and fertility care in the United Kingdom:
      demand and supply.
AB  - OBJECTIVE: To collect data on the demand and provision of fertility care in HIV
      infected couples in the United Kingdom and data on the etiology of subfertility
      in this population. DESIGN: A postal questionnaire survey and audit of causes of
      infertility in HIV-infected women. SETTING: Seventy-four Human Embryology and
      Fertilisation Authority-registered assisted conception units (ACUs) and 294
      genitourinary medicine (GUM) clinics in the United Kingdom were sent
      questionnaires. PATIENT(S): Sixty-five HIV-infected women attending the Research
      Clinic at the Chelsea and Westminster ACU. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Number of ACUs treating HIV-infected patients and number of GUM
      clinics receiving requests for referral, as well as the etiology of subfertility
      in HIV-infected women attending our clinic. RESULT(S): Response rates from ACUs
      and GUM clinics were 93% and 63%, respectively. Fourteen ACUs (20%) were treating
      HIV-infected men; of these, seven (10%) performed sperm washing, but only two
      (3%) tested sperm for HIV after processing, before use. Nine units (13%) treated
      HIV-infected women, but only three ACUs (4%) had separate laboratories for
      handling potentially infected gametes or embryos. Of the 15,211 patients
      registered in 81 GUM clinics, 4% of the men and 16% of the women had requested
      advice on conceiving. An audit of the Chelsea and Westminster HIV fertility
      clinic demonstrated a 40% prevalence of tubal factor infertility in HIV-infected
      women. CONCLUSION(S): Demand is high, and set to increase, but current suboptimal
      practice in some centers is placing unaffected partners and the unborn child at
      risk of seroconversion.

PMID- 16595199
TI  - Human immunodeficiency virus and infertility services: the glass is half full.
AB  - Human immunodeficiency virus-infected couples have demonstrated a strong desire
      to be parents. Despite the willingness of some reproductive endocrinologists to
      provide services to them, a number of barriers to access still confront infertile
      HIV-infected individuals.

PMID- 16595200
TI  - Safeguarding the quality and safety of reproductive services for human
      immunodeficiency virus-positive adults.
AB  - Throughout the world, adults with HIV are living longer, and many are assessing
      their options for reproduction. The growing body of scientific evidence and
      commentary concerning the outcomes of infertility services provided to these
      adults demands systematic summary and long-term surveillance if safety, quality,
      and benefit are to be assured.

PMID- 16595201
TI  - American physicians remain slow to embrace the reproductive needs of human
      immunodeficiency virus-infected patients.
AB  - Nearly 1 million Americans are infected with HIV. Most are living well and
      enjoying productive lives. Yet few programs in the United States permit
      unrestricted access to assisted reproduction for HIV-seropositive patients. Some
      of these individuals have conventional problems causing infertility. Many others
      are attempting to minimize viral transmission to their spouse or offspring.
      European centers remain far ahead of those in the United States in advancing
      techniques and offering services to safeguard the uninfected while providing
      effective, affordable care to the HIV-seropositive patient.

PMID- 16595202
TI  - Human immunodeficiency virus and fertility care: embarking on a path of knowledge
      and access.
AB  - The convergence of medical and social factors in the HIV-infected community has
      produced a growing interest in procreation with the aid of assisted reproductive
      technologies. Meeting the needs of fertile and infertile, concordant and
      discordant couples will require the establishment of multidisciplinary treatment
      centers and research programs to define and provide the safest and most effective
      therapy possible.

PMID- 16595204
TI  - Cytogenetic analysis of human oocytes remaining unfertilized after
      intracytoplasmic sperm injection.
AB  - Oocytes remaining unfertilized after intracytoplasmic sperm injection showed
      12.0% aneuploidy (nondisjunction + unbalanced predivision), 3.4% structural
      aberrations, and 8.5% balanced predivision in fully karyotyped cells. However,
      the frequently observed complete or partial separation of chromatids, most
      probably caused by abortive activation, might complicate the evaluation of
      meiosis I-derived aneuploidy and questions the relevance of balanced predivision.

PMID- 16595205
TI  - Analysis of aromatase and 17beta-hydroxysteroid dehydrogenase type 2 messenger
      ribonucleic acid expression in deep endometriosis and eutopic endometrium using
      laser capture microdissection.
AB  - OBJECTIVE: To investigate mRNA expression of aromatase and 17beta-hydroxysteroid
      dehydrogenase type 2 (17betaHSD2) in epithelial and stromal cells from eutopic
      and ectopic endometrium of patients with deep endometriosis. DESIGN: Prospective
      study. SETTING: University hospital. PATIENT(S): Patients with deep endometriosis
      and fertile women with macroscopically normal pelvic cavities. INTERVENTION(S):
      During surgery, 30 endometrial and 16 endometriotic samples were obtained from 30
      patients with deep endometriosis. Control endometrial samples were obtained from
      24 fertile women with macroscopically normal pelvic cavities who underwent
      laparoscopic tubal ligation or reversal of tubal sterilization. Epithelial cells
      and stromal cells from endometrial or endometriotic tissues were microdissected
      using laser capture microdissection. MAIN OUTCOME MEASURE(S): Expression levels
      of aromatase and 17betaHSD2 mRNA in microdissected epithelial and stromal cells
      were determined using quantitative real-time reverse transcriptase polymerase
      chain reaction. RESULT(S): Aromatase mRNA expression was significantly higher in
      epithelial cells than in stromal cells in both eutopic and ectopic endometrium
      obtained from endometriosis patients. In the ectopic endometrium of 8 patients
      (8/16, 50%), 17betaHSD2 expression was not detected in either epithelial or
      stromal cells. In eutopic endometrium from endometriosis patients, 17betaHSD2
      expression in epithelial cells was significantly increased during the early,
      middle, and late secretory phases compared with the late proliferative phase,
      whereas no significant cyclical difference was detected in control endometrium.
      CONCLUSION(S): Local estrogen concentration may be much higher in epithelial
      cells than in stromal cells in deep endometriotic tissue.

PMID- 16595206
TI  - Subcutaneous injection of depot medroxyprogesterone acetate compared with
      leuprolide acetate in the treatment of endometriosis-associated pain.
AB  - OBJECTIVE: To compare the efficacy and safety of SC depot medroxyprogesterone
      acetate (DMPA-SC 104) with that of leuprolide acetate in treatment of
      endometriosis. DESIGN: Phase 3, multicenter, randomized, evaluator-blinded,
      comparator-controlled trial. SETTING: Clinical trial sites in Canada and United
      States. PATIENT(S): Two hundred seventy-four women with surgically diagnosed
      endometriosis. INTERVENTION(S): Intramuscular injections of DMPA-SC (104 mg) or
      leuprolide acetate (11.25 mg), given every 3 months for 6 months, with 12 months
      of posttreatment follow-up. MAIN OUTCOME MEASURE(S): Reduction in five
      endometriosis symptoms or signs (dysmenorrhea, dyspareunia, pelvic pain, pelvic
      tenderness, pelvic induration); change in bone mineral density (BMD),
      hypoestrogenic symptoms, bleeding, and weight. RESULT(S): The depot
      medroxyprogesterone acetate given SC was statistically equivalent to leuprolide
      in reducing four of five endometriosis symptoms or signs at the end of treatment
      (month 6) and in reducing all five symptoms after 12 months' follow-up (month
      18). Patients in the DMPA-SC 104 group showed significantly less BMD loss than
      did leuprolide patients at month 6, with scores returning to baseline at 12
      months' follow-up. No statistically significant differences in median weight
      changes were observed between groups. Compared with leuprolide, DMPA-SC 104 was
      associated with fewer hypoestrogenic symptoms but more irregular bleeding.
      CONCLUSION(S): Efficacy of DMPA-SC 104 was equivalent to that of leuprolide for
      reducing endometriosis-associated pain, with less impact on BMD and fewer
      hypoestrogenic side effects but more bleeding.

PMID- 16595207
TI  - Preimplantation genetic diagnosis significantly reduces pregnancy loss in
      infertile couples: a multicenter study.
AB  - OBJECTIVE: The inicidence of miscarriage is correlated with maternal age. The
      majority of miscarriages are chromosomally abnormal. The purpose of this study
      was to determine in a large population of infertility patients (>2000 cycles) if
      preimplantation genetic diagnosis (PGD) reduced the rate of spontaneous
      abortions. DESIGN: Multicenter retrospective controlled study. SETTING: One
      hundred IVF centers referring samples to a reference PGD laboratory. PATIENT(S):
      Infertile women. INTERVENTION(S): The spontaneous abortion rate after PGD was
      retrospectively compared to non-PGD cycles from the 2002 American Society for
      Reproductive Medicine-Society for Assisted Reproduction Technology report on IVF
      cycles. MAIN OUTCOME MEASURE(S): Spontaneous abortions and trisomic offspring
      rates. RESULT(S): The study included 2,279 cycles of PGD. The pregnancy rate per
      retrieval was 26.7% (average age 39.6). The mean pregnancy loss for the PGD group
      (0.167) was significantly lower than for the general IVF group (0.215) (P<.001).
      After PGD, the spontaneous abortion rate was 14.1% for ages 35-40, and 22.2% for
      women over 40, compared to 19.4% (P=.03) and 40.6% (P<.001), respectively, in
      controls. The clinical error rate of PGD (1.2%) was significantly lower than
      expected (4.7%) (P<.001). CONCLUSION(S): The data suggests that PGD significantly
      reduces the risk of spontaneous abortions in women undergoing IVF and PGD,
      particularly in women over 40. In addition, PGD may also reduce the risk of
      trisomic offspring.

PMID- 16595208
TI  - Comparison of endometrial and subendometrial blood flows among patients with and
      without hydrosalpinx shown on scanning during in vitro fertilization treatment.
AB  - OBJECTIVE: To compare endometrial and subendometrial blood flows among patients
      with and without hydrosalpinx (HSP) during in vitro fertilization treatment as
      measured by a three-dimensional power Doppler ultrasound. DESIGN: A prospective
      observational study. SETTING: A tertiary assisted-reproduction unit. PATIENT(S):
      Twenty-one patients with HSP were compared with 42 matched controls without HSP.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Endometrial thickness,
      endometrial pattern, endometrial volume, pulsatility index (PI) and resistance
      index (RI) of uterine vessels, and the vascularization index (VI), flow index
      (FI), and vascularization flow index (VFI) of endometrial and subendometrial
      regions were measured on the day of oocyte retrieval. RESULT(S): The proportion
      of the non-multilayered endometrial pattern was significantly higher in the HSP
      group than in the non-HSP group. Patients in the HSP group had significantly
      lower endometrial and subendometrial VI and VFI. Endometrial thickness,
      endometrial volume, uterine PI, uterine RI, and endometrial and subendometrial FI
      were similar between the two groups. No significant differences were observed in
      endometrial and subendometrial VI, FI, and VFI among patients with unilateral and
      bilateral HSP. CONCLUSION(S): A change in endometrial pattern and a decrease in
      endometrial and subendometrial blood flows may be the reasons for impaired
      implantation in patients with HSP.

PMID- 16595209
TI  - Effectiveness of psychosocial group intervention for reducing anxiety in women
      undergoing in vitro fertilization: a randomized controlled study.
AB  - OBJECTIVE: To evaluate the effect of the Eastern Body-Mind-Spirit (EBMS) group
      intervention on anxiety-reduction of Chinese women undergoing IVF. DESIGN:
      Randomized controlled study. SETTING: Tertiary assisted reproduction unit.
      PARTICIPANT(S): Two hundred twenty-seven women undergoing their first cycle of
      IVF treatment. INTERVENTION(S): The intervention group (n = 69) received four
      sessions of EBMS group counseling, while the control group (n = 115) did not
      receive any intervention. MAIN OUTCOME MEASURE(S): State-Trait Anxiety Inventory.
      RESULT(S): Compared with the control group, the intervention group had a
      significant drop in State Anxiety mean score following intervention. A comparable
      number of embryos were transferred for each group, but there was a nonsignificant
      trend of a higher pregnancy rate in the intervention group. CONCLUSION(S): The
      Eastern Body-Mind-Spirit group intervention approach effectively reduces the
      anxiety level of women undergoing IVF treatment.

PMID- 16595210
TI  - Comparison of pronuclear zygote morphology and early cleavage status of zygotes
      as additional criteria in the selection of day 3 embryos: a randomized study.
AB  - OBJECTIVE: Both pronuclear morphology and early zygote cleavage have been used in
      combination with day 3 criteria to predict implantation and pregnancy. However,
      in routine practice, it is impractical to use both these criteria to select
      embryos on day 3. The objective of the present study was to find which of the two
      criteria is more predictive in terms of implantation and pregnancy. DESIGN:
      Randomized study. SETTING: Hospital-based fertility center. PATIENT(S): A total
      of 330 IVF/ICSI patient cycles. INTERVENTION(S): Patients were randomized to two
      groups. The embryos of one group were classified into subgroups A, B, and C based
      on pronuclear morphology (group 1) and the embryos of the second group were
      classified into subgroups A, B, and C based on early cleavage status (group 2).
      MAIN OUTCOME MEASURE(S): Comparisons were made of implantation and pregnancy
      rates between groups 1 and 2, between subgroups within each group, and between
      the corresponding subgroups of groups 1 and 2. Progression of zygotes from day 1
      to day 3 in group 1 was recorded, and retrospective analysis of pronuclear
      morphology of zygotes in group 2 was performed. RESULT(S): The overall
      implantation and pregnancy rates tended to be slightly higher for group 1
      compared to group 2 patients, but not statistically significant. Further, there
      was no significant difference between the corresponding subgroups. Implantation
      and pregnancy rates of subgroup A zygotes from each group were significantly
      higher (P<.01) than the rates of subgroup C. CONCLUSION(S): There was no
      significant difference between the two groups in terms of implantation and
      pregnancy. However, pronuclear morphology is a more satisfactory criterion than
      early cleavage to assist embryo selection on day 3. This is because zygotes with
      early cleavage ability can be identified from their pronuclear morphology. Thus,
      observation for early cleavage on day 1 and assessment of progression of embryos
      on day 2 in addition to pronuclear morphology scoring is not necessary in the
      selection of embryos for transfer on day 3.

PMID- 16595211
TI  - Transabdominal ultrasound-assisted embryo transfer and pregnancy outcome.
AB  - OBJECTIVE: To assess the clinical value of transabdominal ultrasound (TAS)-
      assisted embryo transfer on outcomes of in vitro fertilization--embryo transfer
      (IVF-ET) in comparison to the "clinical touch" method of transcervical embryo
      transfer by one physician and to determine if transabdominal ultrasound should be
      applied to all cases of embryo transfer in this practice. DESIGN: A retrospective
      comparison study. SETTING: A university-based IVF practice. PATIENT(S): Two
      hundred forty-nine patients who underwent transcervical transfer of fresh embryos
      created using autologous oocytes performed by the same physician from July 1,
      2003, to June 30, 2004. INTERVENTION(S): On selected days, at time of embryo
      transfer, transabdominal ultrasound was performed to guide catheter placement
      depth approximately 1 cm from the uterine fundus. MAIN OUTCOME MEASURE(S): The
      presence of at least one gestational sac on ultrasound was compared in the two
      study groups; additionally, the clinical pregnancy rate (presence of fetal
      cardiac activity observed on ultrasound), the ectopic pregnancy rate, the
      biochemical pregnancy rate, and the implantation rate (number of gestational sacs
      identified on ultrasound per number of embryos transferred) between groups was
      evaluated. Characteristics of the two cohorts were analyzed to verify
      similarities between the treatment and control groups, including age of
      recipient, prior IVF history, day of transfer (day 3 or day 5 after retrieval),
      difficulty of transfer, the use of a tenaculum, and the quality and number of
      embryos transferred. RESULT(S): No statistical difference was seen in the
      presence or number of gestational sacs following embryo transfer with or without
      transabdominal ultrasound guidance. CONCLUSION(S): No additional advantage is
      conferred when using transabdominal ultrasound to perform embryo transfer. In
      experienced hands, the "clinical touch" method of embryo transfer yields
      equivalent results to transabdominal ultrasound-guided embryo placement. However,
      in patients with a prior history of difficult uterine sounding or embryo
      transfer, transabdominal ultrasound guidance may still play a role.

PMID- 16595212
TI  - Early cleavage morphology affects the quality and implantation potential of day 3
      embryos.
AB  - OBJECTIVE: To assess the development and implantation potential of early-cleaved
      embryos displaying various morphological patterns. DESIGN: Retrospective
      analysis. SETTING: Private IVF center. PATIENT(S): Embryos obtained from 1,556
      transfer cycles were assessed. Early-cleaved embryos were grouped according to
      their cleavage patterns as: even (1,490); uneven (3,238); and fragmented (768),
      or according to nuclear morphologies as: mononucleation (2,008) and other nuclear
      morphologies; nonmononucleation (3,488). Seven thousand four hundred forty-five
      embryos were late cleaved. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryo
      quality, pregnancy (PR), and implantation rates. RESULT(S): Day 3 embryo quality
      was highest in evenly early-cleaved embryos and in those displaying
      mononucleation. Early-cleaved embryos displaying fragmentation and late-cleaved
      embryos yielded the poorest day 3 quality. Early cleavage cycles displayed higher
      PR and implantation rate than late cleavage with the exception of other nuclear
      morphologies, in which similar outcome was obtained. Mononucleated early-cleaved
      embryos implanted at a higher frequency than early-cleaved embryos displaying
      other nuclear morphologies. CONCLUSION(S): The morphology of early cleavage
      correlates to day 3 embryo quality and implantation rate.

PMID- 16595213
TI  - Usefulness of intraovarian artery pulsatility and resistance indices measurement
      on the day of follicle aspiration for the assessment of oocyte quality.
AB  - OBJECTIVE: To examine the correlation between the pulsatility and resistance
      indices (PI and RI) of the intraovarian artery on the day of follicle aspiration
      and the oocyte quality, intrafollicular oxidative stress, and luteinization.
      Pulsatility index and RI on the day of hCG administration also were measured.
      DESIGN: Prospective study. SETTING: Obstetrics and gynecology department of a
      university medical school in Japan. PATIENT(S): Thirty-five patients in an IVF-ET
      program. INTERVENTION(S): The PI and RI of the intraovarian artery were measured
      by transvaginal color ultrasonographic pulsed wave Doppler on the day of hCG
      administration and the day of follicle aspiration. Follicular fluids and the
      granulosa cells were collected at follicle aspiration. MAIN OUTCOME MEASURE(S):
      The PI and RI of the intraovarian artery blood flow on the day of hCG
      administration and of follicle aspiration, as well as the rate of development of
      mature oocytes, follicular fluid steroid levels, and the incidence of apoptosis
      in the granulosa cells. RESULT(S): The PI and RI on the day of follicle
      aspiration were correlated positively with the rate of mature oocytes retrieved
      (PI: r = 0.429; RI: r = 0.348), were correlated negatively with the incidence of
      apoptotic mural (PI: r = -0.383; RI: r = -0.459) and cumulus (PI: r = -0.378; RI:
      r = -0.469) granulosa cells, and were negatively correlated with the
      concentration of P in the follicular fluid (PI: r = -0.429; RI: r = -0.359). The
      PI and RI on the day of hCG administration were negatively correlated only with
      the total number of retrieved oocytes (PI: r = -0.393; RI: r = -0.374).
      CONCLUSION(S): The PI and RI of the intraovarian artery blood flow measured on
      the day of follicle aspiration may be good indicators of the follicle
      luteinization and oxidation as well as of oocyte quality.

PMID- 16595214
TI  - Value of the sperm deoxyribonucleic acid fragmentation level, as measured by the
      sperm chromatin dispersion test, in the outcome of in vitro fertilization and
      intracytoplasmic sperm injection.
AB  - OBJECTIVE: To determine the prognostic value of sperm DNA fragmentation levels,
      as measured by the sperm chromatin dispersion (SCD) test, in predicting IVF and
      ICSI outcome. DESIGN: Double-blind prospective study. SETTING: University
      affiliated private IVF setting. PATIENT(S): A total of 85 couples undergoing
      infertility treatment with IVF/ICSI. INTERVENTION(S): Analysis of DNA
      fragmentation by the SCD test in 170 aliquots obtained from the ejaculate and
      from the processed semen used for assisted reproductive technologies (ART). MAIN
      OUTCOME MEASURE(S): Percentage of spermatozoa with fragmented DNA was
      statistically correlated with embryo quality and reproductive success. RESULT(S):
      Fertilization rate was inversely correlated with DNA fragmentation (r = -0.245 P
      = .045). Higher DNA fragmentation rate gave an increased proportion of zygotes
      showing asynchrony between the nucleolar precursor bodies of zygote pronuclei
      (73.8% vs. 28.8% P < .001). In addition, the slower embryo development and worst
      morphology on day 6 was correlated with higher sperm DNA fragmentation (47.7% vs.
      29.4% P = .044). We also observed a negative correlation between DNA
      fragmentation and the implantation rate (r = -0.250 P = .042). However, SCD test
      values were not statistically different in cycles that resulted in a pregnancy
      compared with those that did not (33.2 vs. 28.2 and 32.4 vs. 34.7).
      CONCLUSION(S): This is the first report that describes a correlation between
      sperm DNA integrity, as measured by the SCD test, and fertilization rate, embryo
      quality, and implantation rate in IVF/ICSI. The degree of DNA fragmentation was
      inversely correlated with fertilization rate, synchrony of the nucleolar
      precursor bodies' pattern in pronuclei, embryo ability to achieve blastocyst
      stage, and embryo morphological quality. Because SCD test values were correlated
      with embryo quality and blastocyst rate, the lack of correlation between sperm
      DNA fragmentation and pregnancy outcome in IVF might be due to embryo selection
      before transfer. The ability of the SCD test to predict the blastocyst rate after
      IVF/ICSI warrants further study.

PMID- 16595215
TI  - Triploidy formation after intracytoplasmic sperm injection may be a surrogate
      marker for implantation.
AB  - OBJECTIVE: Triploidy after intracytoplasmic sperm injection (ICSI) is due mostly
      to retention of the second polar body. Our interest was to determine the
      predictors of triploidy and to determine whether the presence of triploidy can
      serve as a surrogate marker of implantation for the remaining cohort of zygotes.
      DESIGN: Cohort study. SETTING: Academic research center. PATIENT(S): Infertile
      couples undergoing IVF/ICSI. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Triploid zygote (3PN) rate, implantation rate. RESULT(S): The 3PN rate is a
      significant predictor of implantation rate for the remaining cohort of zygotes.
      The starting and total dose of gonadotropins administered and the total days of
      stimulation are independent predictors of the 3PN rate. CONCLUSION(S): In couples
      with a normal semen analysis undergoing IVF/ICSI, the 3PN rate may serve as a
      surrogate marker of oocyte quality and may be altered by adjusting the
      stimulation protocol.

PMID- 16595216
TI  - Platelet-activating factor acetylhydrolase activity affects sperm motility and
      serves as a decapacitation factor.
AB  - OBJECTIVE: To determine the relationship between platelet-activating factor
      acetylhydrolase (PAFah) content in semen and sperm motility. DESIGN: The PAFah
      levels in semen were measured and correlated with sperm motility. SETTING:
      Clinical laboratory in a private assistant reproductive technology clinic.
      PATIENT(S): Three hundred and twelve men seeking diagnosis and treatment of
      infertility. INTERVENTION(S): Semen samples were collected from 312 healthy
      mature men seeking infertility treatment. Sperm motility and PAFah activity were
      measured in seminal plasma. Data was analyzed by Student's t test and regression
      analysis. MAIN OUTCOME MEASURE(S): PAFah activity and sperm motility. RESULT(S):
      Seminal PAFah content ranged from a low of 179 IU/L to a high of 2,457 IU/L. The
      overall mean PAFah content in semen was 780.59 IU/L. Linear regression analysis
      revealed a significant (R2 = 0.655) and negative relationship between PAFah
      content in semen and sperm motility. Semen specimens with high percent motility
      (> or = 50%) had significantly lower PAFah concentrations (442.03 +/- 14.37 IU/L)
      than those with the lower percent sperm motility (< 50%) (882.16 +/- 18.45 IU/L).
      CONCLUSION(S): The data confirm the presence of PAFah in human semen and that
      activity is significantly and negatively correlated with sperm motility. The
      PAFah is proven to be a candidate for sperm decapacitation factors, whereas PAF
      is qualified to be a candidate for sperm capacitation factors.

PMID- 16595217
TI  - Conventional in vitro fertilization versus intracytoplasmic sperm injection in
      patients with borderline semen: a randomized study using sibling oocytes.
AB  - OBJECTIVE: To determine whether patients with borderline semen should be treated
      with conventional IVF or intracytoplasmic sperm injection (ICSI). DESIGN:
      Randomized study. SETTING: A university medical center in The Netherlands.
      PATIENT(S): One hundred six couples with borderline semen who were undergoing IVF
      and ICSI on sibling oocytes. INTERVENTION(S): Performing IVF and ICSI on sibling
      oocytes. MAIN OUTCOME MEASURE(S): Fertilization and pregnancy rates. RESULT(S):
      One thousand five hundred eighteen oocytes were collected in 106 oocyte
      retrievals: 849 oocytes were randomly allocated to ICSI, of which 761 were
      microinjected, and 669 oocytes were randomly assigned to IVF. In 26 of the 106
      patients, there was fertilization only after ICSI and not after IVF (IVF- group).
      The fertilization rate was 51% (92/182 oocytes). In 78 patients, there was
      fertilization after both IVF and ICSI (IVF+ group); the fertilization rate was
      51% for both the IVF- and ICSI-treated oocytes (271/528 oocytes and 334/658
      oocytes, respectively). In 2 patients, there was no fertilization after either
      IVF (0/6 oocytes) or ICSI (0/9 oocytes). Patients of the IVF+ group had a higher
      total motile sperm count after preparation than did those of the IVF- group. More
      high-quality embryos were obtained after ICSI in patients of the IVF+ group. In
      101 patients, embryo transfer was performed: 26 in the IVF- group and 75 in the
      IVF+ group. No significant differences were found with regard to pregnancy rates
      between those two groups: pregnancy rates were 54% in the IVF- group and 48% in
      the IVF+ group. CONCLUSION(S): Performing ICSI on at least some of the oocytes
      will avoid unnecessary fertilization failure in patients with borderline semen:
      in this study, 26 of 104 cycles (25%) were rescued by ICSI.

PMID- 16595218
TI  - Clomiphene citrate monitoring for intrauterine insemination timing: a randomized
      trial.
AB  - OBJECTIVE: To compare pregnancy rates with two different methods of intrauterine
      insemination (IUI) timing in patients treated with clomiphene citrate (CC).
      DESIGN: Prospective, randomized trial. SETTING: Academic medical center.
      PATIENT(S): One hundred fifty ovulatory, infertile women. INTERVENTION(S):
      Patients were randomized into a luteinizing hormone (LH) surge group or a
      follicle monitoring/human chorionic gonadotropin (hCG) group. All patients
      underwent baseline ultrasound, and took clomiphene citrate, during days 5-9.
      Patients in the LH surge group underwent IUI on the day after a home test for the
      LH surge was positive, whereas those in the hCG group received hCG according to
      ultrasound parameters and underwent insemination 33-40 hours later. Patients
      remained in the same study group for up to three cycles. MAIN OUTCOME MEASURE(S):
      Pregnancy rates per cycle and per patient. RESULT(S): No significant differences
      were found between groups in pregnancy rates per patient or per cycle. The LH
      surge group underwent IUI significantly later than the hCG group. Cancellation
      rates were significantly higher for the LH surge group (31% vs. 11%) and
      attributable mainly to failure to detect an LH surge. The majority of pregnancies
      in both treatment groups occurred in the first cycle. CONCLUSION(S): The decision
      to use hCG for IUI timing should be influenced by factors other than pregnancy
      rates.

PMID- 16595219
TI  - Impact of leuprolide acetate on luteal phase function in women undergoing
      controlled ovarian hyperstimulation and intrauterine insemination.
AB  - OBJECTIVE: To determine if the combination of leuprolide acetate (LA) and human
      menopausal gonadotropin (hMG) results in luteal phase dysfunction. DESIGN: A
      prospective, randomized clinical trial. SETTING: A tertiary care university
      fertility center. PATIENT(S): One hundred thirty-five couples with various
      etiologies of infertility. INTERVENTION(S): Patients were prospectively
      randomized to receive either hMG and intrauterine insemination (IUI) or luteal
      phase down-regulation with LA, hMG, and IUI. MAIN OUTCOME MEASURE(S): Serum
      luteal phase progesterone (P) and luteal phase estradiol (E2) were obtained 9
      days after hCG administration. Twenty-four-hour urinary P and luteinizing hormone
      (LH) were analyzed 9 days after human chorionic gonadotropin (hCG). Endometrial
      biopsies were performed 11 days after hCG and evaluated for luteal phase defects
      (LPD) using Noyes' criteria. RESULT(S): No significant differences in the
      incidence of LPD (11.9% vs. 13.9%), cycle fecundity (16.6% vs. 16.3%), or luteal
      phase hormone profiles were observed between the groups receiving and not
      receiving LA. A significant difference in E2 levels (on the day of hCG
      administration) between cycles with a luteal phase defect (967 pg/mL +/- 106) and
      without a luteal phase defect (1,422 pg/mL +/- 83) was observed (P<.05).
      CONCLUSION(S): Pituitary down-regulation with LA combined with hMG did not result
      in luteal phase dysfunction. The E2 levels on the day of hCG administration in
      both groups were lower in women with documented luteal phase defects.

PMID- 16595220
TI  - Levels of apoptosis in human granulosa cells seem to be comparable after therapy
      with a gonadotropin-releasing hormone agonist or antagonist.
AB  - OBJECTIVE: To compare levels of apoptosis in granulosa cells from women treated
      with the gonadotropin-releasing hormone (GnRH) agonist triptorelin or the GnRH
      antagonist cetrorelix. DESIGN: Randomized, prospective study. SETTING: University
      hospital. PATIENT(S): Thirty-two women undergoing assisted reproduction
      techniques after ovulation induction with recombinant follicle-stimulating
      hormone (FSH) plus GnRH agonist or antagonist. INTERVENTION(S): Granulosa cells
      were isolated from follicular aspirates after oocyte removal. MAIN OUTCOME
      MEASURE(S): Apoptosis was assessed with Annexin V binding assay, terminal
      deoxynucleotidyl transferase (TdT)-mediated nick-end labeling (TUNEL) assay, flow
      cytometric analysis of DNA, and ultrastructural analysis of cell morphology in
      transmission electron microscopy. Serum and follicular hormonal levels were also
      determined. RESULT(S): Annexin V binding and TUNEL assays revealed comparable
      percentages of apoptosis in the two groups under investigation. Analysis of DNA
      histograms revealed a similar cell cycle distribution in the two groups.
      Ultrastructural analysis only occasionally displayed patterns of chromatin
      margination in apoptotic cells. The mean concentrations of all the follicular
      fluid steroid hormones evaluated (E2, T, and P) were significantly lower in the
      GnRH antagonist-treated group. CONCLUSION(S): Therapy with a GnRH agonist or
      antagonist is associated with comparable levels of apoptosis in granulosa cells.

PMID- 16595221
TI  - Effects of two forms of combined oral contraceptives on carbohydrate metabolism
      in adolescents with polycystic ovary syndrome.
AB  - OBJECTIVE: To compare the effects of combined oral contraceptives (OCs)
      containing cyproterone acetate or desogestrel on insulin sensitivity in
      adolescents with polycystic ovary syndrome (PCOS). DESIGN: A prospective
      randomized clinical trial. SETTING: Outpatient gynecological clinic of Aretaieion
      University Hospital. PATIENT(S): Thirty-six adolescent girls with
      hyperandrogenism and six or less menses in the preceding 12 months.
      INTERVENTION(S): Patients were separated in two groups: group A (n = 18) received
      0.15 mg of desogestrel plus 0.030 mg of ethinyl E2 daily; and group B (n = 18)
      received 2 mg of cyproterone acetate plus 0.035 mg of ethinyl E2 daily, for 21
      days followed by a 7-day rest, for 12 months. MAIN OUTCOME MEASURE(S): Hirsutism
      score, lipid, androgen, and sex hormone-binding globulin (SHBG) levels were
      evaluated at baseline. An oral glucose tolerance test (OGTT) was performed and
      metabolism indices, based on previously studied mathematical formulas, were
      assessed at baseline and at 12 months. RESULT(S): After 12 months of treatment,
      the homeostasis model assessment index of insulin resistance increased
      significantly in both groups. The fasting glucose-to-insulin ratio and predicted
      insulin sensitivity index decreased in group B. The delta of the area under the
      OGTT curve for insulin and predicted first and second phase insulin secretion
      indices increased significantly only in group B. CONCLUSION(S): We conclude that
      treatment of adolescent girls with PCOS with the two combined OCs administered,
      results in unfavorable changes of insulin sensitivity. In addition, cyproterone
      acetate is associated with an increase of insulin secretion and hyperinsulinemia.

PMID- 16595222
TI  - A randomized controlled trial of the efficacy of rosiglitazone and clomiphene
      citrate versus metformin and clomiphene citrate in women with clomiphene citrate
      resistant polycystic ovary syndrome.
AB  - OBJECTIVE: To compare the efficacy of rosiglitazone and clomiphene citrate (CC)
      with metformin and CC in women with CC-resistant polycystic ovary syndrome
      (PCOS). DESIGN: Randomized controlled trial (RCT). SETTING: A university teaching
      hospital in Jeddah, Saudi Arabia. PATIENT(S): Twenty-five women with CC-resistant
      PCOS. INTERVENTION(S): Twelve women were assigned to the rosiglitazone and CC
      group, and 13 women were assigned to the metformin and CC group for three
      treatment cycles. The first cycle was started on the first day of the period with
      either rosiglitazone (4 mg twice daily) or metformin (500 mg three times daily)
      and continued for three cycles. Clomiphene citrate (100 mg) from the third day
      for 5 days was added to each cycle. MAIN OUTCOME MEASURE(S): Ovulation rate,
      number of follicles and estradiol (E2) on day 12 of the cycle, pregnancy rate,
      and changes in fasting glucose, serum insulin, HbA(1C), total testosterone (T),
      free T, luteinizing hormone (LH), follicle-stimulating hormone (FSH),
      dehydroepiandrosterone sulfate (DHEAS), delta4-androstenedione (delta4-A), sex
      hormone-binding globulin (SHBG), insulin-like growth factor (IGF)-1, insulin-like
      growth factor binding protein (IGFBP)-1, and IGFBP-3. RESULT(S): No significant
      differences were found in the baseline characteristics of both groups. Ovulation
      rate was significantly higher in the rosiglitazone and CC group (18 out of 28
      cycles [[64.3%]]) than the metformin and CC group (12 out of 33 cycles [[36.4%]])
      (P=.035). Similarly, statistically significant differences were found in the
      number of follicles > or =14 mm in the rosiglitazone and CC group (2.2 +/- 1)
      compared with the metformin and CC group (1.1 +/- 0.9) (P=.02) and E2 on day 12
      of the cycle in the rosiglitazone and CC group (1,991 +/- 1,389 pmol/L) compared
      with the metformin and CC group (548 +/- 327) (P<.001). The pregnancy rate was
      also higher in the rosiglitazone and CC group (6 out of 12 [[50%]] women) than
      the metformin and CC group (5 out of 13 [[38.5%]] women), but did not reach
      statistical significance (P=.58). Both groups showed no significant changes in
      fasting plasma glucose or HbA(1C) or IGFBP-3 values. However, in both groups,
      fasting serum insulin, total T, free T, LH, DHEA-S, delta4A, and IGF-1 levels
      decreased significantly, and SHBG and IGFBP-1 exhibited significant increases.
      CONCLUSION(S): These findings suggest that short-term use of rosiglitazone and CC
      is more efficacious than metformin and CC in ovulation induction in women with CC
      resistant PCOS.

PMID- 16595223
TI  - Efficacy of a new oral contraceptive containing drospirenone and ethinyl
      estradiol in the long-term treatment of hirsutism.
AB  - OBJECTIVE: This study represents long term clinical and biochemical results and
      the response of different body parts to medical therapy with oral ethinyl
      estradiol/drospirenone combination in hirsute patients with or without polycystic
      ovary syndrome (PCOS). DESIGN: Prospective, open, controlled clinical study.
      SETTING: Outpatients at Erciyes University Medical School. PATIENT(S): Fifty
      women with moderate to severe hirsutism were recruited. Two women were lost to
      follow-up. INTERVENTION(S): Women were treated with 3 mg of drospirenone and 30
      microg of ethinyl estradiol for 12 cycles. MAIN OUTCOME MEASURE(S): Hirsutism was
      assessed at 6-month intervals using the Ferriman-Gallwey (F-G) scoring system.
      Serum FSH, LH, total and free testosterone (T), androstenedione (A),
      dehydroepiandrosterone sulfate (DHEAS), estradiol (E2), and sex-hormone binding
      globulin (SHBG) levels at 6 and 12 months of therapy were compared with baseline
      values. RESULT(S): Total mean FG score declined by 67% and 78% after 6 and 12
      months, respectively. Improvement was most prominent on the chest and abdomen,
      followed by the upper lip and chin. The lowest effect was observed on the back
      and arms. Serum levels of total and free T and A decreased, whereas SHBG levels
      increased significantly after 6 and 12 months when compared with baseline levels.
      CONCLUSION(S): Drospirenone/ethinyl estradiol combination exerts significant
      antiandrogenic activity and is effective in improving facial hirsutism. The
      beneficial effect is most obvious after six cycles and continues thereafter at a
      slower rate.

PMID- 16595224
TI  - Y-chromosome microdeletions and recurrent pregnancy loss.
AB  - OBJECTIVE: To determine the prevalence of Y-chromosome microdeletions in
      recurrent pregnancy loss (RPL) couples as compared with couples with male factor
      infertility and fertile couples. DESIGN: Controlled clinical study. SETTING:
      Andrology laboratory and RPL clinic. PATIENT(S): Seventeen men from RPL couples,
      18 men from couples with a live birth and no history of miscarriages, and 10 men
      from couples with male factor infertility. INTERVENTION(S): Buccal smears for Y
      chromosome microdeletion testing. MAIN OUTCOME MEASURE(S): The DNA was tested for
      microdeletions in the proximal AZFc region by polymerase chain reaction (PCR).
      RESULT(S): Fourteen of the 17 men (82%) tested had microdeletions in one or more
      of the four segments studied. Two of the 10 male factor infertility patients
      (20%) had microdeletions in 2 different segments. None of the 18 fertile men had
      any microdeletions in the 4 segments of the proximal AZFc region studied.
      CONCLUSION(S): The prevalence of the Y-chromosome microdeletions in the proximal
      AZFc region was much higher in men from RPL couples than from fertile or
      infertile couples. Although these patients are from a tertiary referral center
      that may skew the population and findings, one may consider Y-chromosome
      microdeletion testing particularly of the AZFc region in the evaluation of RPL
      couples when all other tests fail to reveal the etiology.

PMID- 16595225
TI  - Embryonic karyotype in recurrent miscarriage with parental karyotypic
      aberrations.
AB  - OBJECTIVE: To assesses chromosomal aberrations in the abortus in recurrent
      miscarriage, in the presence of parental chromosomal aberrations. DESIGN:
      Retrospective comparative cohort study. SETTING: Tertiary referral unit in
      university hospital. PATIENT(S): One thousand one hundred eight patients with 3
      16 miscarriages before 20 weeks gestation; 113 patients with and 995 without
      chromosomal aberrations. INTERVENTION(S): Karyotyping by standard G-banding
      techniques of both parents, and of 205 abortuses collected at curettage. MAIN
      OUTCOME MEASURE(S): The incidence of the euploidic and aneuploidic abortuses
      according to the parental karyotype. RESULT(S): Two hundred three abortuses were
      successfully karyotyped. In 164 embryos of patients with no parental chromosomal
      aberrations, 23.2% (38/164) had chromosome aberrations. Of the 39 abortuses
      karyotyped in patients with chromosomal aberrations, 17 had normal karyotypes, 8
      had balanced translocations, 2 had inversions identical to the parents, and 12
      (30.8%) had abnormal karyotypes. This difference is not statistically significant
      (odd ratio 1.47, 95% confidence interval 0.63-3.39). Only 4 of the 39 karyotyped
      abortuses had an unbalanced translocation. CONCLUSION(S): Parental karyotyping
      was not particularly predictive of a subsequent miscarriage as a result of
      chromosomal aberrations as 43.5% of abortuses were euploidic, and the parental
      aberration was only passed on to the abortus in 10% of cases.

PMID- 16595227
TI  - Utero-ovarian ultrasonographic and Doppler flow analyses in female childhood
      cancer survivors with regular menstruation and normal circulating follicle
      stimulating hormone levels.
AB  - OBJECTIVE: To analyze the hormonal, ultrasonographic, and color Doppler
      parameters in a population-based follow-up study of female childhood cancer
      survivors with regular menstrual cycle and normal early follicular FSH values.
      DESIGN: Controlled, prospective clinical study. SETTING: University hospital.
      PATIENT(S): Twenty-eight female patients affected by a malignant tumor during
      childhood and 14 age-matched healthy controls. INTERVENTION(S): Hormonal,
      ultrasonographic, and color Doppler analyses. MAIN OUTCOME MEASURE(S): In the
      midluteal phase of the cycle, the patients underwent hormonal assay of
      gonadotropins, E2, and P; ultrasonographic evaluation of the uterine and ovarian
      volume, the endometrial thickness, and of the corpus luteum characteristics;
      color Doppler analysis of uterine, intraovarian, and periluteal arteries.
      RESULT(S): A greater uterine volume and a better utero-ovarian vascularization
      was observed in controls in comparison with cancer survivors. In patients who
      suffered from childhood malignancies the P values were lower than in controls. On
      the basis of circulating P (> or < 20 nmol/L) values, we divided the former group
      in ovulatory and nonovulatory patients. We observed that even if there were no
      differences between ovulatory cancer survivors and controls, the nonovulatory
      group showed a reduced uterine volume associated with elevated resistance at the
      level of uterine and intraovarian arteries. Among these two groups the time
      elapsed between the diagnosis of cancer and menarche was shorter in nonovulatory
      than in ovulatory women, and was directly correlated with both uterine volume (r
      = 0.660) and ovarian volume (r = 0.597). CONCLUSION(S): Ultrasonographic and
      Doppler analyses may noninvasively study the subtle utero-ovarian modification
      after anticancer therapies.

PMID- 16595226
TI  - A model for predicting age at menopause in white women.
AB  - OBJECTIVE: To develop a model to predict the age at natural menopause and the
      risk for premenopausal hysterectomy. DESIGN: Cross-sectional study. SETTING:
      Multicenter study. PATIENT(S): A total of 1,345 white women. INTERVENTION(S): Ten
      single nucleotide polymorphisms (SNPs) of seven estrogen (E)-metabolizing genes
      (i.e., catechol-O-methyltransferase, 17-beta-hydroxysteroid dehydrogenase type 1,
      cytochrome P-450 [CYP] 17, CYP1A1, CYP1B1, CYP19, and E receptor [ER] alpha) were
      analyzed by sequencing-on-chip-technology. MAIN OUTCOME MEASURE(S): Patients'
      reproductive and medical histories were ascertained and correlated to genotypes.
      RESULT(S): The model incorporates the number of full term pregnancies, the body
      mass index (BMI), a history of breast surgery, and the presence of CYP17 and
      CYP1B1-4 polymorphisms as well as the BMI to predict age at natural menopause and
      the risk for undergoing premenopausal hysterectomy. CONCLUSION(S): We present the
      first model to date, which can predict age at natural menopause and the risk for
      undergoing premenopausal hysterectomy based on genotype information and personal
      history.

PMID- 16595228
TI  - Genotype distribution of estrogen receptor-alpha, catechol-O-methyltransferase,
      and cytochrome P450 17 gene polymorphisms in Caucasian women with uterine
      leiomyomas.
AB  - OBJECTIVE: To evaluate the association between the presence of uterine leiomyomas
      and three functional single nucleotide polymorphisms (SNPs) of the estrogen
      receptor alpha (ESR1), catechol-O-methyltransferase (COMT), and cytochrom P450 17
      (CYP17A) genes, which have been described to modify the estrogen metabolism.
      DESIGN: Prospective case control study. SETTING: Academic research institution.
      PATIENT(S): One hundred thirty women with clinically and surgically diagnosed
      uterine leiomyomas and 139 population controls. INTERVENTION(S): Peripheral
      venous puncture. MAIN OUTCOME MEASURE(S): Polymerase chain reaction and
      pyrosequencing were performed to genotype women with respect to the ESR1 IVS1-397
      T/C (PvuII), COMT G158A, and the CYP17A 34T-->C SNPs. RESULT(S): Comparing women
      with uterine leiomyomas and controls, no statistically significant differences
      with respect to allele frequency and genotype distribution were ascertained for
      ESR1 IVS 1-397 T/C (PvuII) (P=0.9 and P=0.6, respectively), COMT G158A (P=0.3 and
      P=0.6, respectively), and CYP17A 34T-->C (P=0.1 and P=0.5, respectively). When
      all two-way interactions of investigated SNPs were ascertained, no significant
      interactions were observed. In a multivariate model, no SNP was significantly
      associated with leiomyomas. CONCLUSION(S): Carriage of the ESR1 IVS1-397 T/C
      (PvuII), COMT G158A, and the CYP17A 34T-->C SNPs is not associated with the
      susceptibility to uterine leiomyoma in a Caucasian population.

PMID- 16595229
TI  - Preconception sex selection demand and preferences in the United States.
AB  - OBJECTIVE: Preconception sex selection for nonmedical reasons raises important
      moral, legal, and social issues. The main concern is based upon the assumption
      that a widely available service for sex selection will lead to a socially
      disruptive imbalance of the sexes. For a severe sex ratio distortion to occur,
      however, at least two conditions have to be met. First, there must be a
      significant preference for children of a particular sex, and second, there must
      be a considerable interest in employing sex selection technology. Our objective
      was to ascertain such demand and preferences among the United States general
      population. DESIGN: Cross-sectional web-based survey. SETTING: United States
      general population. PATIENT(S): One thousand one hundred ninety-seven men and
      women aged 18 to 45 years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Web
      based questionnaire assessing preferences for sex of children and demand for
      preconception sex selection for nonmedical reasons. RESULT(S): Eight percent of
      respondents would use preconception sex selection technology, 74% were opposed,
      and 18% were undecided. If the sex selection process was simplified to taking a
      pill, 18% would be willing to use such a medication, 59% were opposed, and 22%
      were undecided. In terms of gender choices, 39% of respondents would like their
      first child to be a son, 19% would like their first child to be a daughter, and
      42% had no preference. Overall, 50% wished to have a family with an equal number
      of boys and girls, 7% with more boys than girls, 6% with more girls than boys, 5%
      with only boys, 4% with only girls, and 27% had no preference. CONCLUSION(S):
      Preconception sex selection technology via sperm separation is unlikely to be
      used by the majority of the United States population and is unlikely to have a
      significant impact on the natural sex ratio.

PMID- 16595231
TI  - A simple zeta method for sperm selection based on membrane charge.
AB  - OBJECTIVE: The objectives were: [1] to develop a simple zeta potential method for
      sperm isolation; and [2] to analyze the sperm maturity, morphology, kinematic,
      and DNA parameters. DESIGN: The phenomenon of sticky sperm adhering to slide
      surfaces was adapted for collecting charged sperm. SETTING: Clinical and academic
      research environment. PATIENT(S): Discarded colloid-washed sperm from routine
      laboratory testing (n = 8). INTERVENTION(S): Sperm were centrifuged in serum-free
      medium and collected for analyses. MAIN OUTCOME MEASURE(S): Kinematic parameters,
      DNA integrity, and maturity. RESULT(S): The percentages of mature (73.0% +/- 0.5%
      vs. control 63.5% +/- 0.5% SEM) and DNA intact sperm (85.0% +/- 0.3% vs. 69.5% +/
      0.5%) increased in the male factor subgroup. Strict normal morphology (19.3% +/-
      0.1% vs. 10.0% +/- 0.1%), hyperactivation (7.0% +/- 0.1% vs. 3.6% +/- 0.1%), and
      progressive motility (29.1% +/- 0.1% vs. 19.9% +/- 0.1%) increased by twofold.
      CONCLUSION(S): The zeta method improved sperm parameters associated with
      increased fertilization and pregnancy after assisted reproduction procedures.
      Manipulation from the attaching-detaching process stimulated sperm metabolism
      without causing premature acrosome reactions. Total motility was unchanged
      suggesting a lack of association between total motility and zeta potential.

PMID- 16595230
TI  - Apoptosis of cultured granulosa-lutein cells is reduced by insulin-like growth
      factor I and may correlate with embryo fragmentation and pregnancy rate.
AB  - OBJECTIVE: To correlate apoptosis of cultured human granulosa-lutein cells (GL
      cells) with the outcome of IVF (embryo fragmentation and pregnancy rate) and to
      study the effect of insulin and insulin-like growth factor I (IGF-I) on
      apoptosis. DESIGN: In vitro assays. SETTING: University laboratory and private
      IVF center. PATIENT(S): Eighty-one women undergoing IVF. INTERVENTION(S):
      Purified human GL cells from pooled follicles were cultured for 48 hours in serum
      free media with or without insulin and IGF-I. Cumulus cells and mural GL cells
      were evaluated separately. MAIN OUTCOME MEASURE(S): Detection of apoptosis by
      using caspACE FITC-VAD-FMK, a fluorescent in situ marker for activated caspases;
      embryo fragmentation; and pregnancy. RESULT(S): Age younger than 38 years and
      successful pregnancy were associated with less apoptosis (33.0% +/- 17.2% vs.
      43.2% +/- 18.0% and 30.2% +/- 14.0% vs. 40.4% +/- 19.5%, respectively). There was
      a linear correlation between embryo fragmentation and GL cell apoptosis. Insulin
      like growth factor I decreased apoptosis in a dose-dependent fashion. A
      statistically significant effect (17% decrease) was reached at a dose of 10 nM.
      Insulin (10 nM) caused a small (8%) decrease in apoptosis, but this effect did
      not reach statistical significance. Cumulus cells consistently had <3% apoptosis.
      CONCLUSION(S): [1] Apoptosis of cultured GL cells may be associated with IVF
      outcome and ovarian reserve and [2] IGF-I decreases apoptosis of cultured GL
      cells.

PMID- 16595232
TI  - Comparison of laser-assisted hatching and acidified Tyrode's hatching by
      evaluation of blastocyst development rates in sibling embryos: a prospective
      randomized trial.
AB  - OBJECTIVE: To assess two zona drilling methods in terms of blastocyst development
      rates using sister embryos. DESIGN: Prospective, randomized study. Sister embryos
      of 14 patients were randomly assigned on day 3 to acidified Tyrode's zona
      drilling or to laser zona drilling. After biopsy, subsequent embryo culture until
      the blastocyst stage (day 5) was performed. SETTING: Private fertility center.
      PATIENT(S): Patients undergoing IVF-preimplantation genetic diagnosis.
      INTERVENTION(S): Embryo biopsy using either laser-assisted hatching or acidified
      Tyrode's hatching on sibling embryos and subsequent blastocyst development
      evaluation. MAIN OUTCOME MEASURE(S): Evaluation of blastocyst development in
      terms of degree of expansion and cell number in the inner cell mass and
      trophectoderm. RESULT(S): Blastocyst development rates (and blastocyst quality)
      were similarly high in both the acidified Tyrode's hatching group and the laser
      assisted hatching group. CONCLUSION(S): Laser hatching does not impair embryonic
      development to the blastocyst stage, demonstrating that laser-assisted hatching
      is a suitable alternative to the use of acidified Tyrode's solution for zona
      drilling.

PMID- 16595233
TI  - Multiple peritoneal parasitic myomas after laparoscopic myomectomy and
      morcellation.
AB  - We describe multiple parasitic myomas visualized on laparoscopy in a woman who
      had a previous laparoscopic myomectomy. Location of the myomas suggests
      morcellation as a contributing factor.

PMID- 16595234
TI  - Endoscopic management of cesarean scar pregnancy.
AB  - OBJECTIVE: To describe our experiences with the diagnosis and endoscopic
      treatment of cesarean scar pregnancy. DESIGN: Prospective clinical study.
      SETTING: Tertiary care university hospital. PATIENT(S): Eleven women treated in
      our division between 1999 and 2004 who had been diagnosed with cesarean scar
      pregnancy. INTERVENTION(S): Transvaginal ultrasound was used for diagnosis, and
      endoscopy (laparoscopy and/or hysteroscopy) was used to treat cesarean scar
      pregnancy and preserve fertility. MAIN OUTCOME MEASURE(S): Operative blood loss,
      hospital stay, and time to resolution of serum beta-hCG were recorded. RESULT(S):
      The gestational age at diagnosis ranged between 6 and 11 weeks. Laparoscopic
      treatment was used in four women, hysteroscopic treatment in six women, and one
      woman underwent combined treatment with laparoscopy and hysteroscopy. The average
      blood loss during surgery was 110.9 mL (range, 20-300 mL), and average hospital
      stay was 1.7 days (range, 0.25-3 days). No complications occurred, and no blood
      transfusion was required. All patients' uteri were successfully preserved, and
      serum beta-hCG levels declined to a normal limit within 4 weeks postoperatively.
      CONCLUSION(S): When the diagnosis of cesarean scar pregnancy is made in the first
      trimester, endoscopy can be an alternative surgical treatment; the prognosis is
      good, and fertility can be preserved.

PMID- 16595235
TI  - Successful twin pregnancy in a patient with complete uterine septum corrected
      during cesarean section.
AB  - OBJECTIVE: To describe a successful in vitro fertilization (IVF) twin pregnancy
      in a patient with complete uterine septum who underwent partial correction during
      cesarean section. DESIGN: Case report. SETTING: An IVF unit at a university
      hospital. PATIENT(S): A 29-year-old female patient with complete uterine septum
      undergoing IVF-intracytoplasmic sperm injection. INTERVENTION(S): In vitro
      fertilization-intracytoplasmic sperm injection with single embryo transfer to
      each uterine cavity. MAIN OUTCOME MEASURE(S): Pregnancy course and outcome.
      RESULT(S): Both transferred embryos underwent implantation, resulting in twin
      pregnancy with a single embryo in each hemi-uterus. Cesarean section was
      performed at 34 weeks' gestation. Two healthy neonates were born. Resection of
      the uterine septum by electrocauterization was attempted during cesarean section.
      Diagnostic hysteroscopy performed 6 months later demonstrated the presence of the
      uterine septum reaching approximately 40% of the cavity. CONCLUSION(S): Whether
      prophylactic metroplasty should be performed in patients with uterine septae
      without prior history of miscarriage or pregnancy complications is still under
      debate. Successful implantation and fetal development might occur without prior
      metroplasty, as described in our case report. Metroplasty during cesarean section
      might be only partly successful because part of the septum might be confined in
      the stretched gravid uterus.

PMID- 16595236
TI  - Preimplantation genetic diagnosis of leukocyte adhesion deficiency type I.
AB  - OBJECTIVE: To describe the application of preimplantion genetic diagnosis (PF to
      a carrier couple for leukocyte adhesion deficiency type I disease (LAD-1), to
      achieve a healthy pregnancy. DESIGN: Case report. SETTING: Reproductive center
      and university hospital. PATIENT(S): A couple in which both partners were
      carriers for LAD-1; the female partner carried a G400A substitution in exon 4,
      and the male partner carried a C562T substitution in exon 5 in the CD18 gene.
      INTERVENTION(S): Day-3 cleavage-stage biopsy after standard in vitro
      fertilization (IVF) and genetic analysis of blastomeres for two mutations, along
      with a marker from chromosome 21. MAIN OUTCOME MEASURE(S): Birth of a child
      unaffected with LAD-1. RESULT(S): Fifteen oocytes were retrieved, of which 10
      were fertilized; eight embryos were suitable for embryo biopsy. After genetic
      analysis, three embryos were found to be unaffected. According to embryo
      morphology, two embryos were transferred, resulting in the birth of an unaffected
      child. CONCLUSION(S): This is the first report of preimplantion genetic diagnosis
      for LAD-1. The successful birth of a healthy child provides evidence that for
      carrier couples of diseases for which traditional prenatal diagnosis and the
      decision of whether to terminate a pregnancy might not be acceptable, the
      application of PGD provides an alternative.

PMID- 16595237
TI  - Meiotic arrest at the midpachytene stage in a patient with complete azoospermia
      factor b deletion of the Y chromosome.
AB  - OBJECTIVE: To study the meiosis of a patient with complete azoospermia factor
      (AZF)b deletion of the Y chromosome. DESIGN: Case report. SETTING: La Conception
      University Hospital, Marseille, France. PATIENT(S): One azoospermic patient.
      INTERVENTION(S): Yq deletion testing, testicular sperm extraction, and meiotic
      study with immunocytochemistry. MAIN OUTCOME MEASURE(S): Abnormal synapsis rates
      in spermatocytes. RESULT(S): We found that most spermatocytes were at an early
      stage of meiosis. Half of the meiotic germ cells analyzed showed asynapsis, which
      was mostly extended or total. Discontinuity in the synaptonemal complex was seen
      in one third of the meiotic cells analyzed. An unusually small number of normal
      pachytene nuclei were found, all at early pachytene substages. CONCLUSION(S):
      This is the first demonstration that the synaptic process is impaired in a man
      with complete deletion of the AZFb interval. Our findings provide evidence that
      the pachytene checkpoint is situated at the midpachytene substage in humans.

PMID- 16595238
TI  - Septate uterus with cervical duplication and a longitudinal vaginal septum: a
      mullerian anomaly without a classification.
AB  - OBJECTIVE: To report a rare uterine anomaly of a septate uterus, double cervix,
      and double vagina. DESIGN: Case report. SETTING: A university-based reproductive
      endocrinology center. PATIENT(S): A 20-year-old nulligravida with primary
      infertility. INTERVENTION(S): Clinical examination and surgical resection of a
      vaginal septum with hysteroscopic examination of both hemicavities. MAIN OUTCOME
      MEASURE(S): Description and treatment for a rare uterine anomaly and a subsequent
      literature search. RESULT(S): Successful resection of vaginal septum and
      subsequent spontaneous pregnancy. CONCLUSION(S): This rare anomaly is not
      explained by classic embryologic teaching and is not described by the
      classification system currently used to describe mullerian anomalies.

PMID- 16595239
TI  - Age-related decline in sperm deoxyribonucleic acid integrity in patients
      evaluated for male infertility.
AB  - The purpose of this study was to analyze the relationship of male age and DNA
      integrity in men presenting for investigation of infertility. We found that men
      45 years and older had significantly greater DNA fragmentation than younger men.

PMID- 16595240
TI  - Gamete donation: a question of anonymity.
AB  - The key global issue surrounding gamete donation is not the well-rehearsed known
      vs. anonymous donation argument but rather one of providing patients with a
      flexible dual-track system (i.e., ability to know or not to know donor identity),
      complete with psychosocial support and education that enables them to make well
      informed choices that benefits all stakeholders present and future.

PMID- 16595241
TI  - The Duarte (N314D) variant in the GALT gene has no effect on in vitro
      fertilization outcome.
AB  - We assessed the effect of the Duarte (N314D) variant in the GALT gene on in vitro
      fertilization outcome measures. Our data do not definitely exclude variants in
      the GALT gene as factors influencing outcome, but the lack of suggestive evidence
      makes it difficult to justify a larger, more definitive study.

PMID- 16595242
TI  - A randomized study of laparoscopic chromopertubation with lipiodol versus saline
      in infertile women.
AB  - Eighty-eight infertile patients undergoing laparoscopy were randomized to undergo
      chromopertubation with lipiodol or with normal saline. The cumulative probability
      of conception at 1, 3, and 6 months following laparoscopy was not statistically
      different between the lipiodol group (21%, 31% , and 43%, respectively) and the
      saline group (18%, 21%, and 33%, respectively).

PMID- 16595243
TI  - Defining the curve when initial levels of human chorionic gonadotropin in
      patients with spontaneous abortions are low.
AB  - Because lower initial hCG concentrations are associated with slower rates of
      decline in spontaneous abortions, the aim of this study was to provide a detailed
      description of the expected rates of hCG decline in patients presenting with very
      low initial hCG levels and who ultimately were confirmed to have spontaneous
      abortions. When initial levels lie between 50 and 500 mIU/mL, the slowest
      expected percentage decline ranges from 12% to 24% in 2 days and from 34% to 68%
      in 7 days.

PMID- 16595244
TI  - Letrozole induction of ovulation in women with clomiphene citrate-resistant
      polycystic ovary syndrome may not depend on the period of infertility, the body
      mass index, or the luteinizing hormone/follicle-stimulating hormone ratio.
AB  - Letrozole induction of ovulation in clomiphene citrate-resistant women with
      polycystic ovary syndrome is associated with an ovulation rate of 54.6% and
      pregnancy rate of 25%. There was no significant difference between letrozole
      responders and nonresponders in age, period of infertility, body mass index,
      waist circumference, LH, FSH, or LH/FSH ratio.

PMID- 16595245
TI  - Ovulation jumping from the left to the right ovary in two successive cycles may
      increase the chances of pregnancy during intrauterine insemination and/or in
      vitro fertilization natural cycles.
AB  - Identification of the ovary from which ovulation takes place in two consecutive
      menstrual cycles results in one of four ovulation patterns, contralateral and
      ipsilateral ovulations on the right or on the left ovary. Our data suggest that
      IVF and IUI treatment in cycles in which development of the dominant follicle
      occurs in the right-sided ovary--and ovulation took place from the left-sided
      ovary in the preceding cycle (contralateral right-sided ovulation)--is likely to
      show the best pregnancy outcome.

PMID- 16595246
TI  - Administration of alternate day triptorelin for controlled ovarian
      hyperstimulation is cost effective.
AB  - Gonadotropin-releasing hormone agonists in an alternate-day dosage resulted in
      similar clinical pregnancy rates as the daily protocol. No premature
      luteinization was reported in either group. Total GnRH agonist dosage in the
      alternate-day protocol was significantly reduced.

PMID- 16595247
TI  - Endometrial, subendometrial, and ovarian stromal blood flow in patients treated
      with two different doses of recombinant human chorionic gonadotropin.
AB  - The effects of two different doses of recombinant hCG on blood flow to the uterus
      and ovary on the day of oocyte retrieval were studied by three-dimensional
      Doppler ultrasonography in 60 women during IVF treatment. There were no
      differences in all the indices of endometrial, subendometrial, and ovarian
      stromal blood flow in women who had received 250 microg or 500 microg of
      recombinant hCG for final oocyte maturation.

PMID- 16595248
TI  - A polymorphism of the interleukin 1 receptor antagonist is not associated with
      polycystic ovary syndrome in Caucasian women.
AB  - In a prospective case-control study we investigated the association of a common
      polymorphism of the interleukin 1 receptor antagonist gene (IL-1 RA) with the
      occurrence and the clinical characteristics of polycystic ovary syndrome (PCOS).
      Allele frequencies did not vary statistically significantly among women with PCOS
      and healthy controls or within the PCOS group with respect to their clinical
      characteristics.

PMID- 16595249
TI  - Increased ammonium in culture medium reduces the development of human embryos to
      the blastocyst stage.
AB  - The objective of this prospective study was to evaluate the effect of ammonium
      accumulated in sequential media and determined by enzymatic spectrophotometric
      method on the blastocyst development in 281 human embryos from 100 stimulated and
      natural in vitro fertilization (IVF) cycles. Ammonium concentration was increased
      in 62% of cycles and was correlated negatively with the blastocyst development
      after classical IVF, but not after intracytoplasmic sperm injection (ICSI).

PMID- 16595250
TI  - How many of the items in the polycystic ovary syndrome can be validated
      statistically?

PMID- 16595251
TI  - How many of the items in the polycystic ovary syndrome can be validated
      statistically?

PMID- 16595253
TI  - Posttreatment azoospermia in cancer patients is subgroup dependent.

PMID- 16595255
TI  - Etiology of Fitz-Hugh and Curtis syndrome?

PMID- 16595257
TI  - PGD--a model to evaluate efficacy?

PMID- 16595259
TI  - Seasonal rhythms and secondary sex ratios.

PMID- 16595262
TI  - Intrarater variation--more studies are needed.

PMID- 16595263
TI  - Intrarater variation--more studies are needed.

PMID- 16595264
TI  - Assessment of the pregnant trauma patient.
AB  - Although less than 10% of pregnant patients are likely to experience some type of
      physical trauma, injury is the leading non-obstetric cause of maternal mortality.
      The assessment and resuscitation of the injured pregnant patient must take into
      account the specific needs of both the mother and the foetus. This paper will
      review the physiology of pregnancy, discuss recent changes in assessment and
      resuscitation, and identify special injuries and issues specific to the pregnant
      trauma patient.

PMID- 16595266
TI  - Re: Soft drinks, childhood overweight, and the role of nutrition educators: let's
      base our solutions on reality and sound science.

PMID- 16595265
TI  - Protective effects of garlic sulfur compounds against DNA damage induced by
      direct- and indirect-acting genotoxic agents in HepG2 cells.
AB  - The aim of this study was to assess the antigenotoxic activity of several garlic
      organosulfur compounds (OSC) in the human hepatoma cell line HepG2, using comet
      assay. The OSC selected were allicin (DADSO), diallyl sulfide (DAS), diallyl
      disulfide (DADS), S-allyl cysteine (SAC) and allyl mercaptan (AM). To explore
      their potential mechanisms of action, two approaches were performed: (i) a pre
      treatment protocol which allowed study of the possible modulation of drug
      metabolism enzymes by OSC before treatment of the cells with the genotoxic agent;
      (ii) a co-treatment protocol by which the ability of OSC to scavenge direct
      acting compounds was assessed. Preliminary studies showed that, over the
      concentration range tested (5-100 microM), the studied OSC neither affected cell
      viability nor induced DNA damage by themselves. In the pre-treatment protocol,
      aflatoxin B1 genotoxicity was significantly reduced by all the OSC tested except
      AM. DADS was the most efficient OSC in reducing benzo(a)pyrene genotoxicity. SAC
      and AM significantly decreased DNA breaks in HepG2 cells treated with
      dimethylnitrosamine. Additionally, all the OSC studied were shown to decrease the
      genotoxicity of the direct-acting compounds, hydrogen peroxide and methyl
      methanesulfonate. This study demonstrated that garlic OSC displayed antigenotoxic
      activity in human metabolically competent cells.

PMID- 16595272
TI  - Evaluating food stamp nutrition education: issues and opportunities.
AB  - Food Stamp Nutrition Education (FSNE) is an optional component of the Food Stamp
      Program aimed at improving food choices of program participants. The last decade
      has seen a dramatic expansion in FSNE, accompanied by increased interest in FSNE
      evaluation. The Society for Nutrition Education, as a leader in nutrition
      education research, has worked collaboratively with federal partners to improve
      FSNE evaluation. This is the first in a 3-part series of papers presented in this
      issue of the Journal of Nutrition Education and Behavior. The series reviews the
      issues, priority needs, and opportunities identified through this process;
      explains our current focus on the development of a brief measure assessing FSNE
      relevant dietary behaviors; and describes plans for measurement development.

PMID- 16595273
TI  - Evaluating food stamp nutrition education: a view from the field of program
      evaluation.
AB  - The purpose of this paper is to review current approaches and issues in the field
      of program evaluation that apply to the effort of improving the evaluation of
      Food Stamp Nutrition Education (FSNE). As nutrition educators respond to
      increasing demands for accountability and measuring results, there are challenges
      to consider, as well as opportunities to capture. This paper includes a focus on
      the internal and external functions of evaluation, with attention given to
      evaluation's internal use and value in improving practice. A list of 10 building
      blocks is offered as essential for planning useful and credible evaluation of
      FSNE.

PMID- 16595274
TI  - Evaluating food stamp nutrition education: process for development and validation
      of evaluation measures.
AB  - The purpose of this paper is to describe a process for developing and validating
      outcome measures relevant to dietary quality behaviors targeted by Food Stamp
      Nutrition Education (FSNE). The ultimate goal is a measure that is valid,
      reliable, sensitive to change, and practical for use for a wide variety of FSNE
      evaluation purposes. The development process has incorporated input from FSNE
      stakeholders at the federal and state level and follows a systematic, research
      driven approach that incorporates both qualitative and quantitative research and
      includes methods for identification of subject domains, selection of evaluation
      items, initial pretesting, and reduction of items. This type of research
      establishes the trustworthiness of new evaluation measures.

PMID- 16595276
TI  - Evaluation of a USDA nutrition education program for low-income youth.
AB  - OBJECTIVE: Examine effectiveness of a state's Youth Expanded Food and Nutrition
      Education Program (EFNEP) and assess the validity of the federal impact indicator
      method for reporting program outcomes. DESIGN: A randomized, controlled field
      trial of 229 groups with 5,111 youth, 9-12 years old, in community settings.
      INTERVENTION: 6- to 8- hour, 7-lesson education experience with food preparation
      and tasting, an education experience typical of EFNEP in California. OUTCOME
      MEASURES: US Department of Agriculture (USDA) impact indicators: nutrition
      knowledge, eating a variety of foods, food selection, and food preparation and
      safety practices. ANALYSIS: Analysis of covariance model controlling for pretest,
      gender, age, and ethnicity, with group nested in condition. RESULTS: Organizing
      responses by impact indicators, treatment participants made significant gains on
      the posttest compared to controls for 3 of 4 indicators (P < .008 to P < .0001).
      Gains were made by 34 to 68% of youth participants for 4 indicators. The impact
      indicator method for federal reporting compared favorably with results from a
      randomized controlled trial with groups nested in conditions. CONCLUSION AND
      IMPLICATIONS: This is the first report in the literature of (1) a large
      evaluation study of Youth EFNEP and (2) an estimate of the validity of the USDA
      impact indicator method for reporting program outcomes.

PMID- 16595275
TI  - Do implementation intentions help to turn good intentions into higher fruit
      intakes?
AB  - OBJECTIVE: The present study examined (1) whether respondents who were encouraged
      to make implementation intentions to eat more fruit increased their fruit
      intakes, as measured by three measures of fruit intake; (2) whether the effects
      of implementation intentions on fruit intake were dependent on positive goal
      intentions at baseline; and (3) the respondents' commitment to perform their
      implementation intentions. DESIGN: Dutch adults (n = 535) were randomly assigned
      to either receive implementation intention instructions or not. Two
      questionnaires were completed with a 1.5-week time interval. Respondents in the
      implementation intention condition were asked to form implementation intentions
      to eat an extra serving of fruit per day during one week. RESULTS: Respondents in
      the implementation intention group reported a high frequency of eating an extra
      serving of fruit per day. The implementation intention effect on frequency of
      extra fruit did not depend on goal intention at baseline. The more committed
      respondents were to carrying out their implementation intention, the more likely
      they were to increase their fruit intake. CONCLUSION: These results provide some
      indications that implementation intentions could be a useful strategy to induce a
      short-term increase in fruit intake.

PMID- 16595277
TI  - It just really clicked: participant-perceived outcomes of community nutrition
      education programs.
AB  - OBJECTIVE: To understand participant-perceived outcomes of community nutrition
      education programs by low income adults. DESIGN: A grounded theory approach using
      qualitative interviews. SETTING: Rural and urban communities in New York State
      and Pennsylvania. PARTICIPANTS: 18 current and past participants in nutrition
      education programs for low income adults. PHENOMENA OF INTEREST: Participants'
      perceived outcomes of community nutrition education programs. ANALYSIS:
      Qualitative analysis derived from the constant comparative method. RESULTS:
      Participants described program experiences in three linked thematic areas: (1) a
      range of motives for program enrollment; (2) current roles, challenges and
      resources as program contexts; and (3) participant-perceived outcomes experienced
      throughout the program that were linked to their motives for enrolling. Short-
      and medium-term outcomes, especially social outcomes, were important to
      participants; positive experiences were linked to later behavior change by
      participants, even among those who did not initially report change. CONCLUSIONS
      AND IMPLICATIONS: Participant-perceived outcomes and program satisfaction were
      linked to enrollment motives and modified by whether participants' current worlds
      provided resources to put learning into practice. Participant inputs such as
      enrollment motives and resources should be included in planning models, assessed
      at multiple points, matched to expected program outcomes, and used to guide
      teaching.

PMID- 16595278
TI  - Determining the food irradiation beliefs of community nutrition educators: do
      beliefs influence educational outreach?
AB  - OBJECTIVE: To develop an instrument to measure the food irradiation beliefs of
      community nutrition educators and to determine the influence of those beliefs on
      food irradiation educational outreach. DESIGN: Survey development, cross
      sectional telephone survey. SETTING: Cooperative Extension Program. PARTICIPANTS:
      All Family and Consumer Sciences (FCS) county extension agents serving in the
      most populated counties in Texas (n = 134, response rate = 99%). These
      participants may not be representative of all FCS extension agents. VARIABLES
      MEASURED: Food irradiation beliefs and educational outreach as well as selected
      demographic variables. ANALYSIS: To determine validity and reliability of the
      instrument, factor analysis and Cronbach's alpha were conducted, respectively. To
      determine if food irradiation beliefs influenced food irradiation educational
      outreach, logistic and multiple regression analyses were conducted, with
      significance set at P < .05. RESULTS: The instrument had adequate reliability;
      two belief scales were identified through factor analysis, referred to as Safety
      Beliefs and Understanding Beliefs. Additionally, regression analysis suggested
      that educators' beliefs about food irradiation influenced the amount of food
      irradiation education they provided. CONCLUSIONS AND IMPLICATIONS: Results
      suggest that educators' beliefs about the safety and their understanding of food
      irradiation are predictors of the educational outreach they provide about it,
      indicating the potential value of professional development regarding food
      irradiation.

PMID- 16595279
TI  - Missouri's students respond to healthy foods with enthusiasm.

PMID- 16595280
TI  - Teaching nutrition concepts through service learning.

PMID- 16595281
TI  - Development and evaluation of educational materials promoting local Colorado
      foods.

PMID- 16595282
TI  - Food stamp nutrition education sets the stage for food stamp nutrition education
      research.

PMID- 16595285
TI  - Predicting fruit consumption: cognitions, intention, and habits.
AB  - OBJECTIVE: To study predictors of fruit intake in a sample of 627 adults. DESIGN:
      Potential predictors of fruit intake were assessed at baseline, and fruit intake
      was assessed at two-week follow-up with self-administered questionnaires
      distributed by e-mail. SETTING: The study was conducted among Dutch adult members
      of an Internet research panel. PARTICIPANTS: A random sample of 627 adults aged
      18-78. VARIABLES MEASURED: Attitudes, subjective norms, self-efficacy, expected
      pros and cons, habit strength, intention, and fruit intake. Fruit intake was
      assessed with a validated food-frequency questionnaire. ANALYSIS: Hierarchical
      linear and logistic regression analyses. Alpha < .05 was considered statistically
      significant. RESULTS: Sex, attitudes, subjective norms, perceived pros, different
      self-efficacy expectations, and habit strength were significantly associated with
      the intention to eat two or more servings of fruit per day. Age, intentions, and
      habit strength were significant predictors of consumption of two or more servings
      of fruit per day. CONCLUSIONS AND IMPLICATIONS: The results confirm that Theory
      of Planned Behavior constructs predict fruit intake, and that habit strength and
      different self-efficacy expectations may be additional determinants relevant to
      fruit intake. Because habitual behavior is considered to be triggered by
      environmental cues, fruit promotion interventions should further explore
      environmental change strategies.

PMID- 16595286
TI  - Impact of a cost constraint on nutritionally adequate food choices for French
      women: an analysis by linear programming.
AB  - OBJECTIVE: To predict, for French women, the impact of a cost constraint on the
      food choices required to provide a nutritionally adequate diet. DESIGN:
      Isocaloric daily diets fulfilling both palatability and nutritional constraints
      were modeled in linear programming, using different cost constraint levels. For
      each modeled diet, total departure from an observed French population's average
      food group pattern ("mean observed diet") was minimized. RESULTS: To achieve the
      nutritional recommendations without a cost constraint, the modeled diet provided
      more energy from fish, fresh fruits and green vegetables and less energy from
      animal fats and cheese than the "mean observed diet." Introducing and
      strengthening a cost constraint decreased the energy provided by meat, fresh
      vegetables, fresh fruits, vegetable fat, and yogurts and increased the energy
      from processed meat, eggs, offal, and milk. For the lowest cost diet (ie, 3.18
      euros/d), marked changes from the "mean observed diet" were required, including a
      marked reduction in the amount of energy from fresh fruits (-85%) and green
      vegetables (-70%), and an increase in the amount of energy from nuts, dried
      fruits, roots, legumes, and fruit juices. IMPLICATIONS: Nutrition education for
      low-income French women must emphasize these affordable food choices.

PMID- 16595287
TI  - Assessing food system attitudes among youth: development and evaluation of
      attitude measures.
AB  - OBJECTIVE: To design and pilot a questionnaire for assessing youth attitudes
      about the food system. DESIGN: Nutrition educators provided important topics for
      food system education through a survey using the Delphi method. The resulting
      questionnaire of attitude scales was piloted with high school students. SETTING:
      The Delphi survey of nutrition educators was conducted through the mail and
      electronically. A paper and pencil questionnaire was administered to high school
      students in Family and Consumer Science classes. PARTICIPANTS: Delphi
      participants were members of the Society for Nutrition Education's Division of
      Sustainable Food Systems. A convenience sample of high school students completed
      the pilot questionnaire. VARIABLES MEASURED: Scales measured attitudes about
      farmland protection, participation in the local food system, hunger in the United
      States, organic agriculture, and environmental issues related to food. ANALYSIS:
      Factor analysis was used to identify constructs. The internal consistency of each
      resulting scale was assessed using Cronbach's alpha. RESULTS: Reliability of
      attitude scales ranged from .59 to .73. CONCLUSIONS AND IMPLICATIONS: Attitude
      scales were created for the purpose of assessing youth thoughts and beliefs about
      the local or regional food system. Such assessments can serve as a starting point
      for food system educators interested in developing effective curricula on food
      system topics.

PMID- 16595288
TI  - The impact of homeless shelters on food access and choice among homeless families
      in Minnesota.
AB  - OBJECTIVE: To determine how and where homeless families access food, and to
      determine factors that influence food choice. DESIGN: Seven focus groups (90
      minutes each) were conducted by two moderators and audio-taped. SETTING: Two
      homeless shelters serving families. PARTICIPANTS: Fifty-three parents or
      guardians (M = 11; F = 42) with children 3-12 years of age. Most participants had
      completed high school or higher education. PHENOMENON OF INTEREST: Food choice
      and food access among homeless families. ANALYSIS: Transcripts evaluated for
      consistency, coded, and evaluated for dominant themes. RESULTS: Limited cooking
      and storage space, and poor meal timing and food options at the shelters resulted
      in participants developing strategies to alleviate hunger. Strategies used to
      obtain food included using food stamps, stealing food, eating food in grocery
      stores, pawning personal items, using savvy shopping habits, scavenging in
      dumpsters (obtaining items such as food from dumpsters), and sacrificing food for
      children. CONCLUSIONS AND IMPLICATIONS: Homeless families find strategies to
      prevent food insecurity. Food stamp usage is a common strategy, but it often is
      insufficient to meet monthly needs, indicating the need for reevaluation of
      program components. The shelter environment's impact on families' food choices
      suggests a role for nutritionists in ensuring availability of adequate,
      nutritious foods. Future research is needed to evaluate the impact of the shelter
      environment on homeless families' overall nutritional status.

PMID- 16595289
TI  - Adapting and implementing a long-term nutrition and physical activity curriculum
      to a rural, low-income, biethnic community.
AB  - This study adapted an urban-based school nutrition program for delivery in a
      rural community. Specific aims were to adapt the curriculum; expand it to include
      physical activity; determine effectiveness on students' attitudes, knowledge, and
      self-efficacy; and assess teachers' impressions. Three cohorts were established:
      173 students taught by a resource teacher, 170 students taught by classroom
      teachers, and 187 students who did not receive the curriculum. Pre- and posttest
      surveys measured outcomes, and classroom teachers were observed and interviewed.
      The curriculum was shown to be effective in enhancing student outcomes for both
      the resource teacher and classroom teacher cohorts. Teachers reported that
      lessons needed to be simplified and that children enjoyed them. Findings support
      the transferability of an urban-based nutrition curriculum to a rural community
      and the need for students to receive health education annually.

PMID- 16595290
TI  - Woodlands Wisdom: a nutrition program interfacing indigenous and biomedical
      epistemologies.
AB  - The Woodlands Wisdom Nutrition Project represents a proactive approach of Tribal
      Colleges to address food and health concerns of indigenous communities. Befitting
      the unique mission of Tribal Colleges, Woodlands Wisdom has created a food and
      nutrition curriculum where local tribal culture and knowledge interfaces with
      nutrition science principles. A conceptual model of this approach is presented
      and discussed within a cross-cultural context. Although student outcome data are
      not yet reported, the model offers several considerations for nutrition educators
      working within cross-cultural contexts.

PMID- 16595291
TI  - Incorporating problem-based learning into an undergraduate community nutrition
      class.

PMID- 16595292
TI  - Family Fun with New Foods: a parent component to the Food Friends social
      marketing campaign.

PMID- 16595294
TI  - Stimulation of N-linked glycosylation and lipid-linked oligosaccharide synthesis
      by stress responses in metazoan cells.
AB  - Endoplasmic reticulum (ER) stress responses comprising the unfolded protein
      response (UPR) are activated by conditions that disrupt folding and assembly of
      proteins inside the ER lumenal compartment. Conditions known to be proximal
      triggers of the UPR include saturation of chaperones with misfolded protein,
      redox imbalance, disruption of Ca2+ levels, interference with N-linked
      glycosylation, and failure to dispose of terminally misfolded proteins.
      Potentially, ER stress responses can reprogram cells to correct all of these
      problems and thereby restore ER function to normal. This article will review
      literature on stimulation of N-linked glycosylation by ER stress responses,
      focusing on metazoan systems. The mechanisms involved will be contrasted with
      those mediating stimulation of N-linked glycosylation by cytoplasmic stress
      responses. This information will interest readers who study the biological roles
      of stress responses, the functions of N-linked glycans, and potential strategies
      for treatment of genetic disorders of N-linked glycosylation.

PMID- 16595297
TI  - Antigenic and molecular characterization of isolates of the Italy 02 infectious
      bronchitis virus genotype.
AB  - As part of an epidemiological surveillance of infectious bronchitis virus (IBV)
      in Spain, four Spanish field isolates showed high S1 spike sequence similarities
      with an IBV sequence from the GenBank database named Italy 02. Given that little
      was known about this new emergent IBV strain we have characterized the four
      isolates by sequencing the entire S1 part of the spike protein gene and have
      compared them with many reference IBV serotypes. In addition, cross-virus
      neutralization assays were conducted with the main IBV serotypes present in
      Europe. The four Spanish field strains and the Italy 02 S1 sequence from the NCBI
      database were established as a new genotype that showed maximum amino acid
      identities with the 4/91 serotype (81.7% to 83.7%), the D274 group that included
      D207, D274 and D3896 strains (79.8% to 81.7%), and the B1648 serotype (79.3% to
      80%). Furthermore, on the basis of these results, it was demonstrated that the
      Italy 02 genotype had been circulating in Spain since as early as 1997. Based on
      the average ratio of synonymous:non-synonymous (dS/dN) amino acid substitutions
      within Italy 02 sequences, no positive selection pressures were related with
      changes observed in the S1 gene. Moreover, phylogenetic analysis of the S1 gene
      suggested that the Italy 02 genotype has undergone a recombination event. Virus
      neutralization assays demonstrated that little antigenic relatedness (less than
      35%) exists between Italy 02 and some of the reference IBV serotypes, and
      indicated that Italy 02 is likely to be a new serotype.

PMID- 16595298
TI  - Identification of a novel circovirus in Australian ravens (Corvus coronoides)
      with feather disease.
AB  - The complete genome of a novel Circovirus isolated from an Australian raven
      (Corvus coronoides) with feather lesions similar to those that occur in
      psittacine beak and feather disease is reported. Degenerate polymerase chain
      reaction primers were designed to amplify and sequence novel Circovirus DNA from
      affected feathers. Sequence analysis indicated that the tentatively named raven
      circovirus (RaCV) was 1898 nucleotides in size with two major open reading frames
      synonymous with other avian circoviruses, ORF C1 and ORF V1, likely to encode a
      putative capsid protein (Cap) and replicase-associated protein (Rep),
      respectively. In common with other circoviruses was the conservation of several
      nucleotide structures and amino acid motifs implicated in virus replication.
      Comparison with other members of the Circoviridae demonstrated that RaCV shares
      the greatest sequence homology with canary circovirus (CaCV) and pigeon
      circovirus (PiCV) and was more distantly related to the beak and feather disease
      virus, goose circovirus, duck circovirus and the two porcine circoviruses, PCV1
      and PCV2. Phylogenetic analysis of the genome and the putative Cap and Rep
      proteins provided further evidence of the close relationship of RaCV with CaCV
      and PiCV.

PMID- 16595299
TI  - Use of FTA filter paper for the molecular detection of Newcastle disease virus.
AB  - The feasibility of using Flinders Technology Associates filter papers (FTA cards)
      to collect allantoic fluid and chicken tissue samples for Newcastle disease virus
      (NDV) molecular detection was evaluated. Trizol RNA extraction and one-step
      reverse transcriptase-polymerase chain reaction (RT-PCR) were used. FTA cards
      allowed NDV identification from allantoic fluid with a titre of 10(5.8) median
      embryo lethal doses/ml. The inactivated virus remained stable on the cards for 15
      days. NDV was detected from FTA imprints of the trachea, lung, caecal tonsil and
      cloacal faeces of experimentally infected birds. RT-PCR detection from FTA cards
      was confirmed by homologous frozen-tissue RT-PCR and virus isolation. Direct
      nucleotide sequence of the amplified F gene allowed prediction of NDV virulence.
      No virus isolation was possible from the FTA inactivated samples, indicating
      viral inactivation upon contact. The FTA cards are suitable for collecting and
      transporting NDV-positive samples, providing a reliable source of RNA for
      molecular characterization and a hazard-free sample.

PMID- 16595300
TI  - Newcastle disease virus (strain Herts 33/56) in tissues and organs of chickens
      infected experimentally.
AB  - Six-week-old susceptible specific pathogen free chickens were infected
      intranasally with the virulent Newcastle disease virus strain Herts 33/56 and the
      levels of virus present in blood, faeces, breast muscle, leg muscle and a pool of
      heart/kidney/spleen were estimated in birds killed humanely at each day post
      inoculation. Highest titres were recorded at day 4 post inoculation when titres
      of virus were 10(6) median egg infectious doses (EID50)/g in the
      heart/kidney/spleen pool, 10(4.2) EID50/g in the leg muscle and 10(4) EID50/g in
      the breast muscle and faeces. A median oral infectious dose of Newcastle disease
      virus strain Herts 33/56 for 3-week-old chickens was estimated to be equivalent
      to 10(4) EID50.

PMID- 16595301
TI  - Heterophil cytokine mRNA profiles from genetically distinct lines of chickens
      with differential heterophil-mediated innate immune responses.
AB  - Previously we demonstrated that increased in-vitro heterophil function translates
      to increased in-vivo resistance to Salmonella enteritidis infections in broilers
      (line A > B). Heterophils produce cytokines and modulate acute protection against
      Salmonella in neonatal poultry. We hypothesized that heterophils from S.
      enteritidis-resistant chickens produce an up-regulated pro-inflammatory
      cytokine/chemokine response compared with S. enteritidis-susceptible chickens. In
      this study, heterophils were isolated 1, 14, and 28 days post-hatch, treated with
      RPMI or phagocytic agonists, and the cytokine/chemokine mRNA expression assessed
      using quantitative real-time reverse transcriptase-polymerase chain reaction. At
      all time-points, heterophils from S. enteritidis-resistant chickens (line A) had
      higher levels of pro-inflammatory cytokine/chemokine mRNA expression upon
      stimulation compared with heterophils from S. enteritidis-susceptible chickens
      (line B). Furthermore, heterophils from line A chickens had decreased mRNA
      expression of transforming growth factor-beta4, an anti-inflammatory cytokine,
      compared with line B. These data indicate a relationship between
      cytokine/chemokine mRNA expression by heterophils and determining overall immune
      competence. Therefore, heterophil functional efficiency, accompanied by
      evaluating cytokine/chemokines produced by heterophils, may be useful biomarkers
      for breeders to consider when developing new immunocompetent lines.

PMID- 16595302
TI  - Infectivity of Histomonas meleagridis in ducks.
AB  - The susceptibility of mule and muscovy ducks to "blackhead" disease caused by
      Histomonas meleagridis was studied, using an experimental intracloacal
      inoculation. Turkeys were used as controls. Morbidity, mortality and body weight
      gain were recorded regularly during the experiments. A direct examination of the
      caecal content was made to determine the absence or presence of the parasite.
      Gross and microscopic lesions were observed on days 7, 14, 21, 28 and 35 post
      infection to evaluate any clinical histomoniosis in ducks and to appraise the
      histomonad's carriage. A scoring system was developed both for gross and
      histological lesions of the caecum and liver. Infected mule and muscovy ducks (n
      = 83) never developed any clinical signs of histomoniasis. Weight gains of
      infected mule and muscovy ducks were similar to those of uninfected ducks. In 67%
      of the ducks (56/83), it was possible to demonstrate the parasite in the caecal
      content throughout the experiment. Typical macroscopic caecal lesions were
      observed in five of the ducks between days 7 and 21 post infection, with a caecal
      necropsy main lesion score (MLS = 1.6) less severe than that in turkeys (MLS =
      2.9). Only caecal histological lesions occurred in six of the cases. Therefore,
      ducks do not seem to be a susceptible host for "blackhead" but may act as carrier
      animals for H. meleagridis. The virulence was apparently not changed, since 67%
      of turkeys (10/15) infected with the caecal content of positive ducks displayed
      classical signs of blackhead disease. Even if H. meleagridis alone does not
      represent a substantial danger in the duck production, its infectivity should to
      be taken into account in the transmission to more susceptible species.

PMID- 16595303
TI  - Attempts to improve on a challenge model for subtype C avian pneumovirus.
AB  - Respiratory disease caused by avian pneumovirus (APV) has a strong negative
      impact on the economy of the turkey industry in many countries. Progress in
      developing vaccines against this infection in the US has been slow partly because
      of the lack of a consistent challenge model to conduct vaccine efficacy studies.
      This study was designed to determine whether in vivo passages of a US isolate of
      APV, designated subtype C (APV-C), would increase virus virulence, leading to
      consistent clinical signs in turkeys. Three different experiments were performed.
      In experiments 1 and 2, a cell culture adapted APV was passaged four times in
      vivo in turkeys. Following each passage, clinical signs were found to increase in
      severity. In addition, inoculated birds were found to shed both APV RNA (by
      reverse transcriptase-polymerase chain reaction) and live virus (by virus
      isolation) at each passage. The mean antibody titres also increased with each
      passage. The results of the second experiment were not in complete agreement with
      those of experiment 1. In the third experiment, APV grown in three different cell
      lines was inoculated into three groups of turkeys. Clinical signs were observed
      in inoculated birds and virus could be isolated from all three groups. The
      results of this preliminary study indicate that in vivo passage of APV-C in birds
      may increase virus virulence, but the results obtained in experiment 2 suggest
      that further studies are needed to confirm this.

PMID- 16595295
TI  - Ribonuclease P: the evolution of an ancient RNA enzyme.
AB  - Ribonuclease P (RNase P) is an ancient and essential endonuclease that catalyses
      the cleavage of the 5' leader sequence from precursor tRNAs (pre-tRNAs). The
      enzyme is one of only two ribozymes which can be found in all kingdoms of life
      (Bacteria, Archaea, and Eukarya). Most forms of RNase P are ribonucleoproteins;
      the bacterial enzyme possesses a single catalytic RNA and one small protein.
      However, in archaea and eukarya the enzyme has evolved an increasingly more
      complex protein composition, whilst retaining a structurally related RNA subunit.
      The reasons for this additional complexity are not currently understood.
      Furthermore, the eukaryotic RNase P has evolved into several different enzymes
      including a nuclear activity, organellar activities, and the evolution of a
      distinct but closely related enzyme, RNase MRP, which has different substrate
      specificities, primarily involved in ribosomal RNA biogenesis. Here we examine
      the relationship between the bacterial and archaeal RNase P with the eukaryotic
      enzyme, and summarize recent progress in characterizing the archaeal enzyme. We
      review current information regarding the nuclear RNase P and RNase MRP enzymes in
      the eukaryotes, focusing on the relationship between these enzymes by examining
      their composition, structure and functions.

PMID- 16595305
TI  - Infectious bronchitis virus S1 gene sequence comparison is a better predictor of
      challenge of immunity in chickens than serotyping by virus neutralization.
AB  - Five strains of infectious bronchitis virus isolated from commercial chickens
      from the state of Pennsylvania, USA during the years 1998 and 1999 were studied.
      The strains were selected for cross-challenge in specific pathogen free chickens
      and virus neutralization in chick embryos on the basis of partial S1 sequence
      amino acid identity values. The partial sequences analysed spanned the
      hypervariable amino terminus region of S1 from amino acid residues 48 to 219,
      based on the Beaudette strain. Using their S1 identity values, the strains
      represented a continuum of genetic, and thus antigenic, relationships. When
      compared with strain PA/5083/99, strain PA/Wolgemuth/98 had high sequence
      identity (96%) followed by PA/171/99 (85%), PA/5344/98 (70%) and PA/1220/98
      (34%). The method of Archetti and Horsfall was used for calculating antigenic
      relatedness values of virus neutralization tests. The same formula was also
      applied to the percentage protection values of cross-challenge tests to derive
      protective relatedness values among the strains. The antigenic relatedness
      values, protective relatedness values, and the partial S1 sequence identity
      values were then analysed. The findings indicated partial S1 sequence identity
      values were more strongly correlated with protective relatedness values and than
      antigenic relatedness values.

PMID- 16595304
TI  - Isolation of a coronavirus from a green-cheeked Amazon parrot (Amazon
      viridigenalis Cassin).
AB  - A virus (AV71/99) was isolated from a green-cheeked Amazon parrot by propagation
      and passage in both primary embryo liver cells derived from blue and yellow macaw
      (Ara ararauna) embryos and chicken embryo liver cells. Electron microscopic
      examination of cytopathic agents derived from both types of cell cultures
      suggested that it was a coronavirus. This was confirmed using a pan-coronavirus
      reverse transcriptase polymerase chain reaction that amplified part of gene 1
      that encodes the RNA-dependent RNA polymerase. The deduced sequence of 66 amino
      acids had 66 to 74% amino acid identity with the corresponding sequence of
      coronaviruses in groups 1, 2 and 3. Several other oligonucleotide primer pairs
      that give PCR products corresponding to genes 3, 5, N and the 3'-untranslated
      region of infectious bronchitis virus, turkey coronavirus and pheasant
      coronavirus (all in group 3) failed to do so with RNA from the parrot
      coronavirus. This is the first demonstration of a coronavirus in a psittacine
      species.

PMID- 16595306
TI  - Genetic detoxification and adjuvant-activity retention of Escherichia coli
      enterotoxin LT.
AB  - Intensive effort has been invested in the search for new effective vaccines that
      can be conveniently administered, with minimal handling of birds. Heat-labile
      enterotoxin (LT) of Escherichia coli H10407 is known as a powerful adjuvant for
      injection and oral administration. However, to use the toxin as an
      immunostimulator in animals, its toxicity must be neutralized. To this aim, we
      modified the LT gene by changing two amino acids (threonine 50 and valine 53) of
      the A subunit to proline. The modified non-toxic LT gene (nLT) was cloned and
      expressed in E. coli as a soluble protein. The protein was efficiently purified,
      reaching levels of about 20 mg active hexameric nLT per litre of induced culture.
      The mutated protein, nLT, and the wild-type protein (wtLT) were administered
      orally to chickens. Those treated with the wtLT exhibited diarrhoea, whereas
      chickens treated with the nLT showed no signs of disease compared with untreated
      birds. The new non-toxic, purified nLT stimulated antibody production in birds
      treated by injection or by oral administration. A field trial with layers that
      included a series of injections of Bovine Serum Albumin mixed with nLT showed
      this modified LT's ability to act as an adjuvant for the antigen mixed with it.
      This study demonstrates the efficient expression and purification of LT, in which
      toxicity was neutralized by genetic modification. Such an approach will enable
      the use of a non-toxic LT molecule with a modified A subunit by the poultry
      industry, to enhance immune responses against antigens co-vaccinated with it.

PMID- 16595307
TI  - Inactivated North American and European H5N2 avian influenza virus vaccines
      protect chickens from Asian H5N1 high pathogenicity avian influenza virus.
AB  - High-pathogenicity (HP) avian influenza (AI) virus of the H5N1 subtype has caused
      an unprecedented epizootic in birds within nine Asian countries/regions since it
      was first reported in 1996. Vaccination has emerged as a tool for use in managing
      the infection in view of future eradication. This study was undertaken to
      determine whether two divergent H5N2 commercial vaccine strains, one based on a
      European and the other a North American low-pathogenicity AI virus, could protect
      chickens against a recent Asian H5N1 HPAI virus. The North American and European
      vaccine viruses had 84 and 91% deduced amino acid sequence similarity to the HA1
      segment of haemagglutinin protein of Indonesia H5N1 HPAI challenge virus,
      respectively. Both vaccine strains provided complete protection from clinical
      signs and death. The vaccines reduced the number of chickens infected and
      shedding virus from the respiratory and intestinal tracts at the peak of virus
      replication. In addition, the quantity of virus shed was reduced by 10(4) to
      10(5) median embryo infectious doses. The use of specific neuraminidase
      inhibition tests allowed identification of infected chickens within the
      vaccinated groups. These data indicate that the currently available H5 vaccines
      of European and North American lineages will protect chickens against the Asian
      H5N1 HPAI virus and reduce environmental contamination by the H5N1 HPAI virus.
      They will be an adjunct to biosecurity measures to reduce virus transmission.

PMID- 16595308
TI  - Defining susceptibility of broiler chicks to colibacillosis.
AB  - This study aimed to define the susceptibility of broilers to colibacillosis
      through quantification of clinical responses and to examine the relationship
      between susceptibility and growth retardation. A challenge experiment was carried
      out twice. In each trial, 192 chicks were challenged intratracheally with
      Escherichia coli (E. coli) at 7 days of age and 160 chicks served as controls.
      Surviving chicks were euthanized at 14 or 15 days. Parameters measured were:
      daily mortality, lesion scores, body weight at 1, 4, 7, 10, 12 and 14 or 15 days
      and feeding behaviour at 6, 11 and 13 days. The results were reproducible, and
      increasing susceptibility to colibacillosis was defined by four categories:
      chicks without lesions, chicks with airsacculitis but no systemic lesions, chicks
      with systemic lesions, and chicks that die. Increasing susceptibility was
      associated with increasing growth retardation, but growth retardation was not
      inevitably linked to challenge with E. coli.

PMID- 16595309
TI  - Development and validation of an anti-N3 indirect immunofluorescent antibody test
      to be used as a companion diagnostic test in the framework of a "DIVA"
      vaccination strategy for avian influenza infections in poultry.
AB  - Avian influenza (AI) infections have become of growing importance both for animal
      and human health. Vaccination has become a recommended tool to support
      eradication efforts and limit the economic losses caused by this disease. The
      "DIVA" system, using a vaccine containing a heterologous neuraminidase to the
      field virus, has been shown to be an effective tool in increasing the resistance
      of birds to field challenge, preventing clinical signs and reducing viral
      shedding in the environment. The companion diagnostic test to the vaccine,
      however, has been only partially validated in the field against one subtype of
      neuraminidase (N1). The present paper presents the results of a full laboratory
      and field validation of the diagnostic test developed to detect antibodies to the
      N3 subtype of AI in vaccinated and unvaccinated chickens and turkeys. Antibody
      kinetic studies conducted in the laboratory have shown that antibodies to the N
      protein may be detected earlier than antibodies to the haemagglutinin. The data
      derived from this extensive validation trial indicate the excellent capability of
      this assay in detecting the presence of active AI infection at an early stage in
      both unvaccinated and vaccinated birds and the lack of interference with vaccine
      induced antibodies.

PMID- 16595310
TI  - Cloacal Lactobacillus isolates from broilers show high prevalence of resistance
      towards macrolide and lincosamide antibiotics.
AB  - Eighty-seven Lactobacillus strains isolated from cloacal swabs of broiler
      chickens derived from 20 different farms in Belgium were identified to species
      level and tested for susceptibility to macrolide and lincosamide antibiotics.
      Five different Lactobacillus species were identified as being predominantly
      present in the cloacae of broilers: Lactobacillus crispatus, Lactobacillus
      salivarius subsp. salivarius, Lactobacillus amylovorus, Lactobacillus gallinarum
      and Lactobacillu sreuteri. Acquired resistance prevalence to macrolides and
      lincosamides was very high in the investigated lactobacilli: 89% of the strains
      were resistant to either or both lincosamide and macrolide class antibiotics. The
      vast majority of these resistant strains (96%) displayed constitutive resistance.
      More than one-half of the macrolide and/or lincosamide resistant strains carried
      an erm(B), erm(C), mef(A), lnu(A) gene or a combination of these genes.

PMID- 16595311
TI  - Clonal stability of Pasteurella multocida in free-range layers affected by fowl
      cholera.
AB  - Detailed longitudinal studies of the genetic stability of Pasteurella multocida
      ssp. multocida, the cause of fowl cholera, have not previously been carried out.
      Consequently, the aim of the present study was to provide detailed information on
      the genetic stability and diversity of P. multocida ssp. multocida in poultry
      flocks over time, enabling new insights into the molecular epidemiology of this
      important poultry pathogen. Longitudinal investigations of the rate and causes of
      mortality were carried out on two free-range layer farms (A and B) over a period
      of 11 months. The total mortality of two flocks, A1 and A2, on farm A were 62 and
      91%, respectively, while the total mortality of a single flock B1 on farm B was
      6%. Postmortem examinations were performed on 708 layers from flocks A1 and A2
      and in 159 from flock B1. Fowl cholera was the main cause of mortality on both
      farms. Pasteurella multocida isolates recovered from layers on both farms were
      characterized phenotypically and genotypically, and 322 isolates were identified
      as P. multocida ssp. multocida. The genetic diversity of 99 isolates from farm A
      and 31 from farm B was characterized by restriction endonuclease analysis and
      amplified fragment length polymorphism analysis. The isolates on each farm had a
      unique restriction endonuclease analysis and amplified fragment length
      polymorphism analysis type, suggesting a single introduction of a successful
      clone. Furthermore the clone on farm A was identical to clones previously
      isolated from outbreaks in the avifauna of Denmark in 1996 and 2001 and in Sweden
      in 1998. This study provides convincing evidence for the clonal stability of
      outbreak clones of P. multocida.

PMID- 16595312
TI  - Rapid detection and characterization from field cases of infectious
      laryngotracheitis virus by real-time polymerase chain reaction and restriction
      fragment length polymorphism.
AB  - A real-time polymerase chain reaction (PCR) assay was developed to specifically
      amplify infectious laryngotracheitis virus (ILTV) DNA from field samples. The 222
      base-pair PCR fragment was amplified using primers located in a conserved region
      of the infected cell protein 4 gene that was demonstrated in this work to
      encompass a single nucleotide polymorphism. Subsequent restriction fragment
      length polymorphism (RFLP) analysis of real-time PCR amplified fragments from a
      range of ILTV isolates using the restriction endonuclease MspI enabled
      differentiation between older ILTV isolates that were prevalent in the 1960s
      prior to the availability of vaccine strains and more recent isolates that
      predominantly are identical to vaccine strains. The assay, using real-time PCR,
      RFLP and sequence analysis, was used to characterize two recent field cases of
      infectious laryngotracheitis from Northern Ireland. One of the field cases was
      demonstrated to be similar to older "wild-type" isolates, while the other field
      case was identified to have a concurrent ILTV infection of both "wild-type" and
      vaccinal type origin. The assay described here using real-time PCR and RFLP
      provides a rapid, specific method that enables detection and characterization of
      ILTV directly from field cases.

PMID- 16595314
TI  - Cultural background and infant survival in Ghana.
AB  - This study is premised on the hypothesis that ethnic specific socio-cultural
      practices such as dietary taboos and food avoidances on mothers and infants, as
      well as perceptions of disease aetiology and treatment patterns may be salient to
      understanding infant mortality differentials in Ghana. To inform policy, the
      paper explores if there are significant ethnic differences in infant survival,
      and whether such differences reflect socio-economic disparities or intrinsic
      factors. Using data from the 1998 Ghana Demographic and Health Survey, there was
      evidence of significant ethnic differences in infant survival at the bivariate
      level. Using Asante mothers as reference, the risk of death was significantly
      higher among children whose mothers were Mole-Dagbani, Grussi, Gruma, Dagarti,
      Fanti and Other Akan. In the multivariate models, however, the higher mortality
      risks associated with these children significantly attenuated after controlling
      for the socio-economic and bio-demographic factors except for the Fanti. The
      findings are discussed with reference to the characteristics and cultural
      theoretical paradigms.

PMID- 16595315
TI  - The determinants of self-rated health among ethnic minorities in Hungary.
AB  - BACKGROUND: The health status of a population is largely determined by the
      mutually interrelated factors of social and financial conditions, and by
      lifestyle, including health-related behaviour. The aim of the study was to
      investigate the factors influencing self-rated health among different ethnic
      minorities living in closed communities in the South-East Hungarian region.
      METHODS: The cross-sectional survey was based on interviewer-administered
      questionnaires on socio-demographic variables, lifestyle and health status. In
      the study 100-120 persons were recruited from Serbian, Croatian, Romanian, German
      minorities and the Hungarian population. Univariate and multivariate logistic
      regression models were used. RESULTS: In the univariate analyses, poor self-rated
      health correlated with all the factors examined except marital status. In the
      multivariate logistic regression model, poor health was found to be significantly
      associated with age, educational level, ethnicity, body mass index and chronic
      diseases. Poor self-rated health was observed in the Croatians and in the
      Hungarian control group. CONCLUSION: In South-East Hungary, demographic
      parameters, especially being a member of a minority, and objective health status
      are highly important determinants of self-rated health. Several of the parameters
      studied in our survey indicated no effect or no special differences within the
      population of the region as concerns of self-rated health; certain other factors,
      however, proved to be special features for the studied ethnic minority,
      justifying the launching of target group-oriented health intervention programmes.

PMID- 16595317
TI  - Choice of medicine and hierarchy of resort to different health alternatives among
      Asian Indian migrants in a metropolitan city in the USA.
AB  - Medical pluralism is common among Asian Indians and the increasing popularity of
      complementary and alternative medicines in the USA has now provided Asian Indian
      immigrants with a wide variety of treatment options to choose from for their
      ailments. Many a times, these options are used simultaneously with each other.
      OBJECTIVE: The objective of the study was to examine the choice of medicine and
      the hierarchy of resort to the different health alternatives by a selected Asian
      Indian immigrant population in the USA. DESIGN: In-depth interviews were
      conducted with 21 informants from a metropolitan city in the USA regarding their
      choice of alternatives and the order in which they choose the different health
      alternatives. Thematic analysis was carried out to interpret the data. RESULTS:
      The different choices for treatment of illness included folk remedies, ayurveda,
      homeopathy and allopathic medicine. Home remedies and Indian medical alternatives
      were the first resort in case of minor ailments while allopathic medicine was the
      first choice for serious and chronic illnesses. CONCLUSIONS: The decision to
      choose from among different alternatives for treatment of illness depends on
      people's beliefs about the severity of illness and the effectiveness of treatment
      options while the hierarchy of resort depends on the kind of illness. The
      hierarchy of resort to treatment followed the counter-acculturative pattern for
      minor illnesses and acculturative pattern for major or chronic illnesses.

PMID- 16595316
TI  - Internalising and externalising behaviours in young adults: Dutch natives and
      Turkish migrants in the Netherlands.
AB  - OBJECTIVE: To compare the prevalence of internalising and externalising behaviour
      of Dutch and Turkish migrant young adults in the Netherlands. We will also assess
      associations with socio-economic position. METHOD: Dutch natives (1,236) and
      Turkish migrants (438), age 18-28, completed the Young Adult Self-Report. Scores
      above the 90th percentile of the distribution of the Dutch sample were defined as
      deviant. RESULTS: Turkish migrants more often reported deviant scores than
      natives for internalising problems, especially for the Anxious/Depressed
      syndrome. For externalising problems, Turkish migrants less often had deviant
      scores for Intrusive Behaviour, whereas Turkish women more often had deviant
      scores for Aggressive and Delinquent Behaviour. Similar results were found for
      comparison between mean scores. After adjustment for socio-economic position, the
      disparities in men remained, whereas disparities in women largely disappeared.
      CONCLUSION: Compared with Dutch young adults, Turkish migrant young adults
      reported more problems. Ethnic disparities were strongly associated with socio
      economic disparities among women, but not among men.

PMID- 16595318
TI  - Ethnicity questions and antenatal screening for sickle cell/thalassaemia [EQUANS]
      in England: a randomised controlled trial of two questionnaires.
AB  - Concepts allied to ethnicity are increasingly coming under question as legitimate
      variables for use in health research. A randomised controlled trial of two
      ethnicity screening questions for ascertaining risk of carrying genes associated
      with sickle cell and thalassaemia illustrates the challenges and limitations of
      assessing an association of social constructs and genetic statuses. OBJECTIVES:
      To evaluate two candidate ethnicity screening questions in antenatal screening
      programmes in low, mixed and high sickle cell prevalence areas, and to identify
      time taken in administration of the questions by use of the following measures:
      (1) Proportions of respondents with missing ethnicity data and/or significant
      changes in ethnic/family origins upon re-interview. (2) Numbers of carriers of
      clinically significant haemoglobin disorders missed by ethnicity screening
      questions. (3) Time taken to explain screening question for sickle cell disease
      (SCD)/thalassaemia and obtain ethnic/family origins. (4) Proportion of clients
      providing usable ethnic/family origins data. (5) Reported ethnic/family origins
      in pregnant women at first booking with midwife. DESIGN: Ten-month (September
      2002-June 2003) questionnaire study with random allocation to two self
      administered ethnicity questions, comparison with laboratory results and results
      from re-interview. The settings were antenatal booking clinics in four
      geographical areas of England of varying expected foetal prevalence of SCD: very
      high (29.75 per 10,000 pregnancies); high (8.2); mixed high and low (1.29); and
      low (0.18). The subjects were 4,559 pregnant women at first booking with midwife.
      RESULTS: Proportions of respondents with missing ethnicity data and/or
      significant changes in ethnic/family origins upon re-interview were 4.33% (CI
      2.63-6.68%) for a category-based question and 9.45% (CI 6.86-12.61%) for a binary
      plus open-ended question. Proportions of carriers missed were 5.74% (CI 2.34
      11.46%) and 9.71% (CI 4.75-17.13%) by category-based and binary plus open-ended
      questions, respectively. Average time taken to ascertain ethnic/family origins
      for screening was between 2.17 and 5.12 minutes in different areas, and up to 15
      minutes at the 95th centile. Usable ethnicity screening data was missing in 2.94%
      of instances. Errors in interpretation or missing data were 3.2% for a category
      based question and 4.71% for a binary plus open-ended ethnicity question.
      Ethnicity Question A produces fewer cases of missing or misinterpreted data (p <
      0.001). CONCLUSIONS: A category-based ethnicity screening question was more
      effective than a binary plus open-ended question. Using the more effective
      question, 5.74% (CI 2.34-11.46%) of significant haemoglobinopathies will be
      missed in a selective screening programme, and 4.33% (CI 2.63-6.68%) of replies
      to an ethnicity screening question will be unreliable when compared to
      information given upon re-interview. In specific carefully circumscribed
      situations, namely, in antenatal screening for sickle cell and thalassaemia, it
      is possible to measure the degree of association between social constructs of
      ethnicity and health status in a manner that may help in effecting policy
      decisions.

PMID- 16595319
TI  - Uncovering the determinants of cardiovascular disease among Indigenous people.
AB  - OBJECTIVE: This paper attempts to delineate an appropriate methodology for
      research into cardiovascular diseases (CVD) in the context of the Australian
      Indigenous population. DESIGN: Our argument proceeds in three main stages of
      critical analysis of the appropriate literature. First we demonstrate the
      extremely complex aetiology of CVD and also argue that, in any population,
      exposure to many of the more important risk factors at an individual or group
      level is generated through social and behavioural factors whose causation,
      persistence and reproduction are both complex and multilayered. Secondly, and
      having established that the aetiology and morbidity of CVD in various populations
      is a product of a complex and interactive hierarchy of biomedical, social and
      political processes, we argue that only research methodologies capable of
      encompassing the complete span of this hierarchy can be expected to generate
      results which are efficacious as a basis for intervention. Thirdly, and most
      importantly, we argue that in the Indigenous context a central and essential
      feature in the development of an appropriate methodology must be to centre
      Indigenous people themselves as the dominant partner in setting the research
      agenda and the conduct of research. RESULTS/CONCLUSIONS: We conclude that an
      appropriate methodology for the elucidation of the aetiology, and sequelae of CVD
      in Indigenous people, would go far beyond 'black box' epidemiology, would
      recognise the essentially social nature of chronic disease by deploying
      appropriate social theory within a transdisciplinary framework and would centre
      Indigenous people as the dominant partner in the research process.

PMID- 16595320
TI  - Changes in tobacco smoking following treatment for cocaine dependence.
AB  - Incorporation of smoking cessation into cocaine treatment programs remains a
      challenge. A major concern is that cocaine abusers may tend to substitute one
      drug for the other. If this is true, successful treatment of cocaine abuse should
      lead to an increase in tobacco smoking. We compared tobacco smoking at admission,
      end of treatment and 9-month follow up for 168 crack cocaine dependent patients
      entering a 12-week outpatient treatment program for substance abuse. Smoking
      cessation was not a part of treatment. As expected cocaine patients improved with
      treatment and showed significant reduction in scores on the Addiction Severity
      Index (ASI). There were no significant changes in number of cigarettes smoked per
      day or scores on the Fagerstrom Test for Nicotine dependence (FTND) from baseline
      to end of treatment or follow-up. Also, there were no differences in the
      proportions of nonsmokers and smokers who changed their smoking habits over the
      treatment and follow up period. At follow up subjects who were abstinent as well
      as those using cocaine showed no changes in tobacco smoking. There is no evidence
      that reduction in crack cocaine smoking following treatment is accompanied by an
      increase in tobacco smoking. It appears that concerns over tobacco being
      substituted for cocaine may be unfounded in this population.

PMID- 16595321
TI  - Understanding patterns of substance abuse treatment for women involved with child
      welfare: the influence of the Adoption and Safe Families Act (ASFA).
AB  - The passage of the federal Adoption and Safe Families Act (ASFA), which calls for
      timely permanency planning for children placed into state foster care systems,
      has led to increased attention to the need for timely and appropriate treatment
      services to families with substance abuse issues who are involved with child
      welfare. Using statewide administrative data collected before and after the
      implementation of ASFA, the present study explores the influence of ASFA, as well
      as other family characteristics, on patterns of treatment service utilization by
      child-welfare involved clients. Findings suggest that in the period following the
      ASFA legislation, mothers entered substance abuse treatment significantly more
      quickly after the start of their child welfare cases, and remained in treatment
      longer, compared to pre-ASFA. No differences in rates of treatment completion
      were found. Results are interpreted in terms of the changing treatment service
      context, enhanced collaboration between child welfare and treatment systems, and
      the possible influence of the legislation on parents' motivation to enter
      treatment.

PMID- 16595322
TI  - Young heroin users in Baltimore: a qualitative study.
AB  - This study describes the characteristics of 67 young heroin users, interviewed
      using a semistructured qualitative questionnaire (QQ) as part of a larger study
      of 18- to 25-year-old heroin users seeking detoxification with buprenorphine at a
      drug treatment center in Baltimore. This new generation of heroin users has a
      different demographic profile compared to older heroin users in this area. Our
      data, supported by data from another clinic and from the Maryland State Alcohol
      and Drug Abuse Administration, seem to indicate that the younger heroin users in
      treatment settings are predominantly White, with a high proportion of women,
      often living in the suburbs. Based on responses to the QQ, all subjects initiated
      heroin use intranasally, usually in a group setting; 75% had subsequently gone on
      to use intravenously. The typical young heroin user in Baltimore Metropolitan
      area appears to be a young White man or woman from a middle/working-class
      background, with exposure to drug use among close contacts while growing up,
      experimenting with gateway drugs with peers before proceeding first to
      intranasal, and then intravenous heroin use, engaging in criminal activities to
      support the habit, repeatedly seeking help with assistance from family, but
      failing to sustain abstinence due to continued exposure to drug using peers and a
      poorly implemented plan of aftercare. Further research should focus on efforts to
      engage peer groups and families in order to improve treatment outcomes in young
      heroin users.

PMID- 16595323
TI  - The association between EIC receipt and employment in a sample of drug using and
      non-drug using TANF recipients.
AB  - This article examines the extent to which Temporary Assistance to Needy Families
      (TANF) recipients file income tax returns and take advantage of the Earned Income
      Credit (EIC), a program specifically designed to increase the economic self
      sufficiency of lower income earners by supplementing earned and other income to
      make working more profitable. This study consisted primarily of Black and
      Hispanic women (n = 317), recruited for a longitudinal study designed to examine
      the effects of welfare reform on drug using and non-drug using welfare
      recipients. At the 2-year mark, 70% of the sample reported having ever filed an
      income tax return, of these 76% had received an EIC. Both hours worked and
      earnings were positively associated with EIC receipt. In this population, EIC
      appears to be a successful mechanism for improving economic self-sufficiency.

PMID- 16595325
TI  - Assessing alcohol and other drug problems (AOD) among sexually transmitted
      disease (STD) clinic patients with a modified CAGE-A: implications for AOD
      intervention services and STD prevention.
AB  - The close link between alcohol and other drug abuse and STD morbidity and the
      positive impact of AOD intervention services in reducing STD morbidity, led the
      New York State Office of Alcoholism and Substance Abuse Services (OASAS) and the
      New York City Bureau of STD Control (BSTDC) to assess the prevalence of AOD
      problems among STD clinic patients. Assessing problematic AOD involvement among
      STD patients was of interest to BSTDC for STD prevention and to OASAS, for new
      AOD case-finding and early intervention. During fall, 2000, 100 STD patients in
      each of the 7 full-time BSTDC clinics in New York City were solicited in clinic
      waiting rooms; eligible patients were screened individually and anonymously with
      a modified CAGE-A (mCA). The mCA asks 4 questions about problematic AOD use
      "ever" (i.e., "lifetime") and currently (i.e., "in the past 30 days) rather than
      "in the past 12 months" of the CAGE and uses two or more "Yes" answers as a
      "positive" screen. The mCA also asks for age, sex, ethnicity, prior AOD
      treatment, and interest in an AOD referral. Only 2 of 704 eligible patients
      refused mCA screening, n = 702. Sixty percent were male, 87.7% Black and/or
      Hispanic, and 69%, <or=35 years old. Of the sample screened, 30.5% were
      "positive" on the "ever" and 16.5%, on "the past 30 days," mCA questions. 13.2%
      reported prior AOD treatment, 1.4% were in AOD treatment or about to start, and
      <1% wanted an AOD referral. Eight of 10 STD patients currently in AOD treatment
      screened positive on the "ever" mCA questions. The AOD prevalence rates observed
      here were deemed high since: 1) CAGE (and CAGE-A) data on general hospital and
      emergency room admissions showed positive screening rates of only 5-14 % and 2)
      only an estimated 6-7% of adults in New York have received any formal
      intervention with an AOD problem, less than half the rate found for treatment
      alone with the STD patients in this study. The results support implementing AOD
      screening and intervention services in STD clinics since an estimated 11,000
      patients annually would screen positive but now are undetected and untreated. As
      AOD intervention services also can reduce risky sexual behavior, providing them
      could expand STD prevention services significantly. Policy, funding, and
      evaluation issues related to implementing AOD intervention services in STD and
      other public health clinics also are discussed.

PMID- 16595326
TI  - Alcohol, employment status, and social benefits: one more piece of the puzzle.
AB  - OBJECTIVES: To examine the role of employment status and the receipt of social
      benefits in the prediction of alcohol use. METHODS: Logistic regression models
      were used to analyze panel data from the National Survey of Families and
      Households (NSFH) 1987-88 and 1991-92. A total of 7,599 respondents who were
      older than 16 years of age in 1987 and did not have a physical or mental
      condition were included in the analysis. The alcohol measures were (a) total
      number of drinks in the past 30 days; and (b) having 5 or more drinks in a day, 4
      or more days in the past 30 days. RESULTS: Employed welfare recipient women have
      a greater likelihood of heavy drinking than other full-time employed. We do not
      find evidence of an association between not being employed (with or without
      benefits) and greater likelihood of engaging in heavy drinking behaviors. Alcohol
      drinking among other employment groups is not significantly different, with the
      exception of retired men who drink less. CONCLUSION: It is important to focus
      attention on women working while receiving welfare, and who may need help
      maintaining their jobs.

PMID- 16595324
TI  - Alcohol use, mental health status and psychological well-being 2 years after the
      World Trade Center attacks in New York City.
AB  - Over the past 30 years, studies have shown that survivors of community-wide
      disasters suffer from a variety of physical and mental health problems.
      Researchers also have documented increased substance use in the aftermath of
      these disasters. In the present study, we examined the relationship between
      alcohol use and mental health status within the context of the terrorist attacks
      on the World Trade Center in New York City (NYC). The data for the present report
      come from a 2-wave panel study of adults living in NYC on the day of the attacks.
      Wave 1 (W1) and Wave 2 (W2) interviews occurred one year and two years after the
      attacks, respectively. Overall, 2,368 individuals completed the W1 survey
      (cooperation rate, 63%) and 1,681 completed the W2 survey (re-interview rate,
      71%). The alcohol use variables examined were binge drinking, alcohol dependence,
      increased days drinking, and increased drinks per day. The outcomes examined
      included measures of posttraumatic stress disorder (PTSD), major depression, BSI
      18-Global Severity and measures of SF12-mental and physical health status. After
      controlling for demographic, stress, and resource factors, multivariate logistic
      regressions indicated that all alcohol measures were related to one or more of
      these outcomes. In particular, binge drinking was related to partial PTSD, while
      alcohol dependence was associated subsyndromal PTSD, severity of PTSD,
      depression, BSI-18 global severity, and SF-12 poor mental health status.
      Increased post-disaster drinking was positively associated with subsyndromal PTSD
      and negatively associated with SF-12 physical health. We discuss reasons for
      these results and the negative consequences that heavy alcohol use may have on
      the postdisaster recovery process.

PMID- 16595327
TI  - Drivers within natural drinking groups: an exploration of role selection,
      motivation, and group influence on driver sobriety.
AB  - Young people consume alcohol almost exclusively in social contexts, but natural
      drinking group dynamics are poorly understood. Our research focuses on the
      drivers' role within natural drinking groups. We conducted breath-test surveys of
      existing groups of young people at the US/Mexico border crossing before they
      headed to Tijuana bars, and surveyed them again upon their return. Results
      indicated an individual's perception of other group member's drinking plans
      predicts drinking intentions to a greater degree for passengers than drivers.
      Additionally, drivers who anticipated heavy drinking among other group members
      returned to the United States with BACs nearly identical to drivers who reported
      that other group members would not drink at all. This suggests drivers were
      resistant to normative pressures to drink. Evidence that group-dynamic variables
      may impact drinking behavior underscores the importance of systematic exploration
      of natural drinking groups. Furthermore, the knowledge gleaned from studying the
      dynamics and decision making processes of natural drinking groups could be used
      to design intervention designed to increase designated driver use and to reduce
      drinking among designated drivers.

PMID- 16595328
TI  - Drunk in public, drunk in private: the relationship between college students,
      drinking environments and alcohol consumption.
AB  - This study examines environmental differences in public (bars) and private
      (parties) drinking settings among of-age (21 and up years of age) and underage
      (18-20 years of age) college students attending college near the US/Mexico
      border. A random telephone survey of graduate and undergraduate students
      attending two large public universities in the southwestern United States was
      conducted during the 2000-2003 academic years. A university-based social science
      research laboratory conducted the telephone interviews with respondents who
      reported an occasion in the past 28 days where alcohol was being consumed (N =
      4,964). The data were analyzed using ordinary least squares multiple regression.
      The results suggests that drinking settings contributed to the amount of alcohol
      consumed by respondents. Additionally, environmental factors contributing to
      drinking vary by setting. In general, having many people intoxicated at an event,
      BYOB parties, playing drinking games, and having illicit drugs available
      contribute to heavier drinking.

PMID- 16595329
TI  - Experimental investigation of an optimization approach to microwave tomography.
AB  - Microwave imaging is an interesting and growing research field with a number of
      medical applications. This paper is based on the first series of experimental
      results using an iterative gradient algorithm based on the finite difference time
      domain (FDTD) method and synthetic pulses. Using our method, the permittivity and
      conductivity of an object are reconstructed layer by layer by minimizing a
      functional consisting of the difference between the measured and calculated
      electric field surrounding the object. This is done by surrounding the object
      with a number of antennas which are all in turn transmitting and receiving. The
      dielectric profiles used in the calculations are then iteratively updated until
      the functional is minimized. Results are presented demonstrating the ability to
      detect metallic and dielectric material in air and water.

PMID- 16595330
TI  - Effects of intensive and moderate cellular phone use on hearing function.
AB  - The purpose of this study is to investigate the effects of radiation emitted by
      mobile phones on the hearing of users. The study was carried out on three groups:
      1) 20 men who have used a cellular phone frequently and spoken approximately 2 h
      per day for four years; 2) 20 men who have used a cellular phone for 10-20 min
      per day for four years; and 3) 20 healthy men who have never used a cellular
      phone (the control group). Brainstem evoked response audiometric (BERA) and pure
      tone audiometric (PTA) methods were used to measure the effects of exposure on
      hearing function of the subjects. In BERA measurements, I-III, III-V, and I-V
      interpeak latencies were evaluated. Interpeak latency of subjects in two
      experimental groups was compared to that of subjects in the control group. The
      BERA results showed no differences among the groups (p > 0.05). In PTA
      measurements, detection thresholds at 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz,
      and 8000 Hz frequencies were measured in all three groups. No differences were
      observed between moderate mobile phone users (10-20 min. per day) and control
      subjects. However, detection thresholds in those who talked approximately 2 h per
      day were found to be higher than those in either moderate users or control
      subjects. Differences at 4000 Hz for both bone and air conduction for right ears,
      and 500 Hz, and 4000 Hz bone and air conduction for left ears were significant
      for mean hearing threshold. This study shows that a higher degree of hearing loss
      is associated with long-term exposure to electromagnetic (EM) field generated by
      cellular phones.

PMID- 16595331
TI  - Effect of millimeter waves on cyclophosphamide induced NF-kappaB.
AB  - Antiapoptotic activity of NF-Kappa B (NF-kappaB) in tumors contributes to
      acquisition of resistance to chemotherapy. The effect of millimeter waves (MMWs)
      on NF-kappaB activation induced by cyclophosphamide (CPA) was studied in the
      spleen of mice. CPA, an anticancer drug, caused a marked increase (58.9-fold) in
      NF-kappaB DNA-binding activity as compared to the control group. No significant
      enhancement in NF-kappaB activity (0.51-fold) was observed when the CPA group was
      also irradiated with MMWs. These results suggest that treatment with MMWs can
      inhibit activation of NF-kappaB induced by chemotherapeutic drugs.

PMID- 16595332
TI  - Coupled field analysis of heat flow in the near field of a microwave applicator
      for tumor ablation.
AB  - Microwave tumor ablation (MTA) offers a new approach for the treatment of hepatic
      neoplastic disease. Reliable and accurate information regarding the heat
      distribution inside biological tissue subjected to microwave thermal ablation is
      important for the efficient design of microwave applicators and for optimizing
      experiments, which aim to assess the effects of therapeutic treatments. Currently
      there are a variety of computational methods based on different vascular
      structures in tissue, which aim to model heat distribution during ablation. This
      paper presents results obtained from two such computational models for
      temperature distributions produced by a clinical 2.45 GHz MTA applicator immersed
      in unperfused ex vivo bovine liver, and compares them with measured results from
      a corresponding ex vivo experiment. The computational methods used to model the
      temperature distribution in tissue caused by the insertion of a 5.6 mm diameter
      "wandlike" microwave applicator are the Green's function method and the finite
      element method (FEM), both of which provide solutions of the heat diffusion
      partial differential equation. The results obtained from the coupled field
      simulations are shown to be in good agreement with a simplified analysis based on
      the bio-heat equation and with ex vivo measurements of the heat distribution
      produced by the clinical MTA applicator.

PMID- 16595333
TI  - Immunotropic influence of 900 MHz microwave GSM signal on human blood immune
      cells activated in vitro.
AB  - In an earlier study we reported that G(o) phase peripheral blood mononulclear
      cells (PBMC) exposed to low-level (SAR = 0.18 W/kg) pulse-modulated 1300 MHz
      microwaves and subsequently cultured, demonstrate changed immune activity
      (Dabrowski et al., 2003). We investigated whether cultured immune cells induced
      into the active phases of cell cycle (G(1), S) and then exposed to microwaves
      will also be sensitive to electromagnetic field. An anechoic chamber of our
      design containing a microplate with cultured cells and an antenna emitting
      microwaves (900 MHz simulated GSM signal, 27 V/m, SAR 0.024 W/kg) was placed
      inside the ASSAB incubator. The microcultures of PBMC exposed to microwaves
      demonstrated significantly higher response to mitogens and higher immunogenic
      activity of monocytes (LM index) than control cultures. LM index, described in
      detail elsewhere (Dabrowski et al., 2001), represents the monokine influence on
      lymphocyte mitogenic response. The results suggest that immune activity of
      responding lymphocytes and monocytes can be additionally intensified by 900 MHz
      microwaves.

PMID- 16595334
TI  - Effect of static electric fields in root cells of Vicia faba (Fabaceae).
AB  - Serial electron microscopic sections were prepared from half-ripened meristematic
      root cells of Vicia faba (Fabaceae) which had been exposed gradually to 700,
      1000, 2500, 3500, and 5000 V/m static electric fields during seven days with and
      without Zn and Cd electrodes. At the end of five weeks, wall loosenings and very
      small nuclei were observed in those root cells which were exposed to static
      electric currents from the lower side of the medium without electrodes, while
      abnormalities in cell formation, e.g., two cells with one nucleus, and GER
      occurrence were present in an electrolytic (Cd upward and Zn downward) medium.
      The cells exposed to a static current from the upper side of the medium had small
      nuclei and abnormal cell divisions in the electrolyte, but in a non-electrolyte
      very large nuclei and thicker cell walls were observed, the cytoplasm was dense
      with GER, pinocytosis was seen filled with mitochondria, and protoplast formation
      with big nuclei was seen in exocytosis.

PMID- 16595335
TI  - Protein kinase C activity in developing rat brain cells exposed to 2.45 GHz
      radiation.
AB  - There is growing concern by the public regarding the potential human health
      hazard due to exposure to microwave frequencies. 2.45 GHz radiation widespread
      use in industry, research, and medicine, and leakage into the environment is
      possible. In order to quantitate this, experiments were performed on developing
      rat brain. Male Wistar 35-day-old rats (n = 6) were used for this study. Animals
      were exposed to 2.45 GHz radiation for 2 h/day for a period of 35 days at a power
      density of 0.344 mW/cm(2) (SAR 0.11 W/kg). The control group was sham irradiated.
      After 35 days these rats were sacrificed and whole brain tissue was isolated for
      protein kinase C (PKC) assay. For morphological study the forebrain was isolated
      from the whole brain and PKC activity was measured using P(32) labeled ATP. Our
      study reveals a statistically significant (p < 0.05) decrease in PKC activity in
      hippocampus as compared to the remaining portion of the whole brain and the
      control group. A similar experiment conducted on hippocampus and the whole brain
      gave a similar result. Electron microscopic study shows an increase in the glial
      cell population in the exposed group as compared to the control group. This
      present study is indicative of a significant change after exposure to the above
      mentioned field intensity. This suggests that chronic exposures may affect brain
      growth and development.

PMID- 16595336
TI  - Influence of ELF sinusoidal electromagnetic fields on proliferation and
      metabolite yield of fungi.
AB  - The response of mycelium proliferation in 12 strains of fungi were tested by
      sinusoidal ELF 50 Hz electromagnetic field treatment in the range B = 0.6-10 mT
      over 10 days. The ratio of experiment/control indicated three types of
      proliferation changes: a) no significant change, b) a strong decrease down to E/C
      = 0.2, c) a maximization of mycelium diameter by treatment at 5-7 mT. According
      to these results, effects can be produced noninvasively by varying either
      magnetic intensities or time of treatment. As yet, systematic bioelectromagnetic
      research using sinusoidal electromagnetic fields (SEMF)-on fermentation of fungi
      is still in its initial stages.

PMID- 16595337
TI  - Receptor-agonist interactions in service-theoretic perspective, effects of
      molecular timing on the shape of dose-response curves.
AB  - Service-theoretic concepts and methods, widely used in other fields (e.g.,
      telecommunication and operations research), are useful also in a biochemical
      setting because the treatment of biocatalysts (enzymes, receptors) as servers and
      their ligands as customers, based on the established formal methods of service or
      queuing theory, may lead to insights and results unobtainable by conventional,
      mass-action-law-based theories. In this article, we apply the service-theoretic
      approach to receptor-agonist systems and show how by changing the stochastic time
      pattern of "operationally relevant" point events (e.g., instants of agonist
      arrival, instants of post-climax agonist departure) a great variety of dose
      response curves may be generated, even in very simple reaction schemes, which,
      according to mass action kinetics, invariably lead to hyperbolic r(A) curves (r
      and A stand for response and agonist concentration, respectively). The molecular
      timing inherent to a hyperbolic response system is not optimal: for instance, at
      the agonist concentration A(50), half of the agonist molecules are rejected
      ("lost") because of unfortunate timing of the arrival events. The fraction of
      lost arrivers can be diminished considerably if the arrivals are better timed:
      "sub-Poisson" arrivals improve the timing and, thus, convert hyperbolic r(A)
      curves into "lifted" nonhyperbolic ones. Conversely, "super-Poisson" arrivals
      make the non-optimal timing in hyperbolic response systems even worse and, thus,
      convert hyperbolic r(A) curves into "depressed" nonhyperbolic ones. Furthermore,
      under special timing conditions, nonhyperbolic r(A) curves can be generated,
      which are partly lifted, partly depressed relative to the reference hyperbola,
      and which resemble in shape well-known nonhyperbolic forms of enzyme and receptor
      kinetics (negatively cooperative, positively cooperative, and sigmoidal
      kinetics). In addition unusual (undulatory and sawtooth-like) r(A) curves can be
      generated solely by changing the temporal pattern of arrival and service
      completion instants. Virtually any shape of dose-response curves may be obtained
      by allowing for probability distributions whose characteristic shape varies with
      their mean; we call such distributions "variomorphic" and apply them to the
      arrival process of agonist molecules.

PMID- 16595338
TI  - Detection of glucose and related analytes by biosensors: a fractal analysis.
AB  - A fractal analysis is used to model the binding and dissociation kinetics of
      connective tissue interstitial glucose, adipose tissue interstitial glucose,
      insulin, and other related analytes on biosensor surfaces. The analysis provides
      insights into diffusion-limited analyte-receptor reactions occurring on
      heterogeneous biosensor surfaces. Numerical values obtained for the binding and
      the dissociation rate coefficients are linked to the degree of heterogeneity or
      roughness [fractal dimension (D(f))] present on the biosensor chip surface. The
      binding and dissociation rate coefficients are sensitive to the degree of
      heterogeneity on the surface. For example, for the binding of plasma insulin, as
      the fractal dimension value increases by a factor of 2.47 from D(f1)=0.6827 to
      D(f2)=1.6852, the binding rate coefficient increases by a factor of 4.92 from
      k(1)=1.0232 to k(2)=5.0388. An increase in the degree of heterogeneity on the
      probe surface leads to an increase in the binding rate coefficient. A dual
      fractal analysis is required to fit the binding kinetics in most of the cases
      presented. A single fractal analysis is adequate to describe the dissociation
      kinetics. Affinity (ratio of the binding to the dissociation rate coefficient)
      values are also presented. Interferents for glucose, such as uric acid and
      ascorbic acid, were also detected by using glucose biosensors based on carbon
      nanotube (CNT) nanoelectrode ensembles (NEEs) (Lin Y, Lu F, Tu Y, Ren Z).

PMID- 16595339
TI  - Constitutive activity of muscarinic acetylcholine receptors.
AB  - We review the literature describing constitutive activity of the five muscarinic
      acetylcholine receptors in native and recombinant systems and discuss the effect
      of constitutive activity on muscarinic pharmacology in the context of modern
      models of receptor activation. We include a summary of mutations found to cause
      constitutive activity and discuss the implications of these data for the
      structure, function, and activation mechanism of muscarinic receptors. Finally,
      we discuss the possible physiological significance of constitutive activity of
      muscarinic receptors, incorporating information provided by targeted deletion of
      each of the muscarinic subtypes.

PMID- 16595340
TI  - Tubulin polymerization modulates interleukin-2 receptor signal transduction in
      human T cells.
AB  - Few data exist on the modulation of cytokine receptor signaling by the actin or
      tubulin cytoskeleton. Therefore, we studied interleukin-2 receptor (IL-2R)
      signaling in phytohemagglutinine (PHA)-pretreated human T cells in the context of
      alterations in the cytoskeletal system induced by cytochalasin D (CyD),
      jasplaklinolide (Jas), taxol (Tax), or colchicine (Col). We found that changes in
      cytoskeletal tubulin polymerization altered the strength of several IL-2
      triggered signals. Moreover, Tax-induced tubulin hyperpolymerization augmented
      the surface expression of the IL-2R ss -chain and enhanced the association of the
      IL-2R beta -chain with cytoskeletal tubulin. The IL-2R beta-chain, in turn, was
      constitutively associated with tubulin and, more weakly, actin. To exclude the
      possibility that these associations are artifacts caused by PHA, we confirmed
      them in T cells from TCR-transgenic DO 11.10 mice stimulated with their nominal
      antigen. We conclude that altered polymerization of cytoskeletal components,
      especially tubulin, is accompanied by modulation of IL-2 signaling at the
      receptor level.

PMID- 16595343
TI  - The death of a person.
AB  - Drawing upon Lynne Baker's idea of the person derivatively possessing the
      properties of a constituting organism, I argue that even if persons aren't
      identical to living organisms, they can each literally die a biological death.
      Thus we can accept that we're not essentially organisms and can still die without
      having to admit that there are two concepts and criteria of death as Jeff McMahan
      and Robert Veatch do. Furthermore, we can accept James Bernat's definition of
      "death" without having to insist, as he does, that persons are identical to
      organisms or that persons can only die metaphorical deaths.

PMID- 16595341
TI  - Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors.
AB  - Conventionally, an allosteric modulator is neutral in respect of efficacy and
      binds to a receptor site distant from the orthosteric site of the endogenous
      agonist. However, recently compounds being ago-allosteric modulators have been
      described i.e., compounds acting both as agonists on their own and as enhancers
      for the endogenous agonists in both increasing agonist potency and providing
      additive efficacy-superagonism. The additive efficacy can also be observed with
      agonists, which are neutral or even negative modulators of the potency of the
      endogenous ligand. Based on the prevailing dimeric concept for 7TM receptors, it
      is proposed that the ago-allosteric modulators bind in the orthosteric binding
      site, but-importantly-in the "other" or allosteric protomer of the dimer. Hereby,
      they can act both as additive co-agonists, and through intermolecular cooperative
      effects between the protomers, they may influence the potency of the endogenous
      agonist. It is of interest that at least some endogenous agonists can only occupy
      one protomer of a dimeric 7TM receptor complex at a time and thereby they leave
      the orthosteric binding site in the allosteric protomer free, potentially for
      binding of exogenous, allosteric modulators. If the allosteric modulator is an
      agonist, it is an ago-allosteric modulator; if it is neutral, it is a classical
      enhancer. Molecular mapping in hetero-dimeric class-C receptors, where the
      endogenous agonist clearly binds only in one protomer, supports the notion that
      allosteric modulators can act through binding in the "other" protomer. It is
      suggested that for the in vivo, clinical setting a positive ago-allosteric
      modulator should be the preferred agonist drug.

PMID- 16595344
TI  - Voluntary euthanasia, physician-assisted suicide, and the goals of medicine.
AB  - It is plausible that what possible courses of action patients may legitimately
      expect their physicians to take is ultimately determined by what medicine as a
      profession is supposed to do and, consequently, that we can determine the moral
      acceptability of voluntary euthanasia and physician-assisted suicide on the basis
      of identifying the proper goals of medicine. This article examines the main ways
      of defining the proper goals of medicine found in the recent bioethics literature
      and argues that they cannot provide a clear answer to the question of whether or
      not voluntary euthanasia and physician-assisted suicide are morally acceptable.
      It is suggested that to find a plausible answer to this question and to complete
      the task of defining the proper goals of medicine, we must determine what is the
      best philosophical theory about the nature of prudential value.

PMID- 16595345
TI  - Totipotency, twinning, and ensoulment at fertilization.
AB  - From fertilization to approximately the sixteenth day of development, human
      embryonic cells are said to have the capacities of totipotency and monozygotic
      twinning, both of which are problematic to a theory of ensoulment at
      fertilization. In this article I will address the problems which these capacities
      pose to such a theory and present an interpretation of the biological data which
      renders ensoulment at fertilization more plausible. I will then argue that not
      only is an ensoulment theory consistent with current biological data on the human
      embryo, but it may offer an explanation for the phenomencon of monozygotic
      twinning.

PMID- 16595346
TI  - Sixteen days? A reply to B. Smith and B. Brogaard on the beginning of human
      individuals.
AB  - When does a human being begin to exist? Barry Smith and Berit Brogaard have
      argued that it is possible, through a combination of biological fact and
      philosophical analysis, to provide a definitive answer to this question. In their
      view, a human individual begins to exist at gastrulation, i. e. at about sixteen
      days after fertilization. In this paper we argue that even granting Smith and
      Brogaard's ontological commitments and biological assumptions, the existence of a
      human being can be shown to begin much earlier, viz., with fertilization. Their
      interpretative claim that a zygote divides immediately into two substances and
      therefore ceases to exist is highly implausible by their own standards, and their
      factual claim that there is no communication between the blastomeres has to be
      abandoned in light of recent embryological research.

PMID- 16595348
TI  - The Addiction Severity Index at 25: origins, contributions and transitions.
AB  - The Addiction Severity Index (ASI) is a multi-dimensional interview used to
      measure the substance use, health, and social problems of those with alcohol and
      other drug problems, both at admission to treatment and subsequently at follow-up
      contacts. This article first discusses the conceptual and practical importance of
      the ASI's multi-dimensional approach to measuring addiction severity, as
      illustrated by two case presentations. The second section of the paper reviews
      how this measurement approach has led to some important findings regarding the
      prediction and measurement of addiction treatment effectiveness. The third
      section describes the historical and practical considerations that have changed
      the instrument over time, details the problems with the instrument, and describes
      our efforts to correct those problems with the ASI-6. Finally, some recent ASI
      data collected from over 8,400 patients admitted to a nationally representative
      sample of U.S. addiction treatment programs are presented.

PMID- 16595349
TI  - Dual diagnosis--policy and practice in Italy.
AB  - In Italy, dual diagnosis issues are affected by distinctive historical pathways.
      Since the end of the 1970s, the addiction field has been starved of psychiatric
      contribution, with the emphasis being on a pedagogical model of substance-related
      disorders and a bio-psycho-social model for mental health. As such, dual
      diagnosis treatment, service models, and research have only been developed in the
      last fifteen years. Substantial training needs with regard to dual diagnosis are
      identified in addiction and mental health professionals, and new graduate and
      undergraduate programs are required. Further research is needed as well as an
      evidence-based health policy from national and regional government.

PMID- 16595350
TI  - Borderline personality and substance use in women.
AB  - The association between borderline personality disorder (BPD) and substance use
      disorder (SUD) was examined in a predominantly psychiatric (77.6%) sample of 232
      women. BPD proved to be a significant predictor of a lifetime diagnosis of SUD
      across four different categories: any SUD (including alcohol); alcohol use; drug
      use; and heroin, cocaine, or poly-substance use. BPD continued to be a predictor
      of SUD even when the effects of other cluster B and all cluster C PDs were
      controlled statistically. Antisocial personality disorder generally yielded
      larger odds ratios than BPD and emerged as a partial mediator of the relation
      between BPD and SUD. Histrionic PD was the only other PD that showed meaningful
      relations with SUD.

PMID- 16595352
TI  - Prevalence and health correlates of gambling problems in substance abuse
      counselors.
AB  - This study examined the prevalence of disordered gambling in substance abuse
      counselors. Participants (N = 328) completed an anonymous self-report survey
      assessing lifetime disordered gambling, past two-month gambling behavior, and
      current mental and physical health. The lifetime prevalence rates of pathological
      and problem gambling in this sample (11.9% and 6.4%, respectively) were higher
      than rates reported in general population surveys. Poorer physical health was
      associated with pathological gambling, but mental health was not. These results
      suggest that substance abuse counselors may benefit from education, prevention,
      and intervention efforts for disordered gambling.

PMID- 16595351
TI  - Validity of the distinction between primary and secondary substance use disorder
      in patients with bipolar disorder: data from the first 1000 STEP-BD participants.
AB  - The validity of a primary/secondary substance use disorder (SUD) distinction was
      evaluated in the first 1000 patients enrolled in the Systematic Treatment
      Enhancement Program for Bipolar Disorder. Patients with primary SUD (n = 116)
      were compared with those with secondary SUD (n = 275) on clinical course
      variables. Patients with secondary SUD had fewer days of euthymia, more episodes
      of mania and depression, and a greater history of suicide attempts. These
      findings were fully explained by variations in age of onset of bipolar disorder.
      The order of onset of SUDs was not linked to bipolar outcomes when age of onset
      of bipolar disorder was statistically controlled. The primary/secondary
      distinction for SUD is not valid when variations in the age of onset of the non
      SUD are linked to course characteristics.

PMID- 16595353
TI  - Predictors of retention in naltrexone maintenance for opioid dependence: analysis
      of a stage I trial.
AB  - Behavioral naltrexone therapy (BNT) was developed to address the shortcomings of
      naltrexone maintenance for opiate dependence and improve compliance by
      integrating several empirically validated methods, including the use of a
      significant other to monitor compliance, voucher incentives, and motivational
      techniques. An uncontrolled Stage I pilot trial (N = 47) of BNT was conducted.
      Baseline demographic and clinical variables were evaluated as predictors of
      retention with univariate tests. Significant predictors were entered together
      into a multiple regression model. Poorer (shorter) retention in treatment was
      associated with methadone use and higher average bags per day of heroin. Other
      variables that became non-significant in multiple regression analysis included
      older age and depressive symptoms. Individuals with greater physiologic
      dependence and/or dependence on longer-acting opiates are at higher risk to drop
      out from naltrexone maintenance and may require a more gradual detoxification and
      more intensive behavioral therapy aimed at enhancing initial compliance.

PMID- 16595354
TI  - Receipt of disability payments by substance users: mental and physical health
      correlates.
AB  - Since 1997, substance users have received disability benefits only for
      impairments apart from their substance use disorders. It is hypothesized that
      substance users currently receiving disability benefits would be more severely
      compromised, medically and/or psychiatrically, than those not receiving
      disability. Enrolling a community sample of 330 heroin and cocaine users between
      January 2002 and January 2004, it was found that individuals who were not
      receiving disability payments had similar mental health scores, current
      depressive symptoms scores, and lifetime rates of major depression compared to
      those receiving payments, but significantly lower rates of bipolar or psychotic
      disorders and psychiatric hospitalization (p < .01). Physically disabled persons
      had lower physical function scores and were more likely to be HIV-infected or
      taking medications regularly (p < .001). The authors conclude that schizophrenia,
      bipolar disorders, and chronic physical illness, but not major depression, are
      qualifying substance users for disability benefits. Longitudinal studies of
      disability status and its effects on the lives of substance users are warranted.

PMID- 16595355
TI  - Differing effects of antipsychotic medications on substance abuse treatment
      patients with co-occurring psychotic and substance abuse disorders.
AB  - This retrospective study of patients treated in a ninety-day, inpatient, dual
      diagnosis treatment program examined antipsychotic effectiveness in this
      population using length of stay in treatment and successful program completion as
      outcome measures. All patients with co-occurring substance dependence and
      schizophrenia or schizoaffective disorder treated with olanzapine, risperidone,
      ziprasidone, and typical depot neuroleptics from January 2001 to December 2003 (N
      = 55) are the subjects of this study. Patients stayed longer in treatment when
      taking risperidone (82 +/- 19 days) or ziprasidone (74 +/- 21 days) compared with
      olanzapine (44 +/- 30 days) or typicals (47 +/- 36 days). Eighty-eight percent of
      risperidone patients and 64% of ziprasidone patients successfully completed the
      program, while only 33% of olanzapine patients and 40% of patients on typicals
      successfully completed the program. Risperidone and ziprasidone were associated
      with significantly better program performance than olanzapine or depot typicals
      in this population. Possible reasons for this difference are discussed.

PMID- 16595357
TI  - Relationship of comorbid substance and alcohol use disorders to disability among
      patients in routine psychiatric practice.
AB  - The primary aim of this study was to present data on the relationship of mental
      and comorbid substance use disorders to work disability and functioning in
      routine psychiatric practice in the United States. Data were used from the 1997
      and 1999 American Psychiatric Institute for Research and Education's Practice
      Research Network Study of Psychiatric Patients and Treatments, totaling 754
      psychiatrists and 3,088 patients. Results found patients with comorbid substance
      use disorders had significantly higher rates of work disability. These findings
      highlight the critical need to address the disturbing lack of substance use
      treatment and rehabilitation services for this population.

PMID- 16595356
TI  - Problem drinking in women evaluated for infertility.
AB  - Clinicians may wish to use the T-ACE, a screening instrument for prenatal risk
      drinking, for their infertile patients. Twenty-eight T-ACE negative and 23 T-ACE
      positive women presenting to an academic infertility clinic completed two
      interviews about their drinking. The 23 T-ACE positive participants were also
      randomized to receive a brief intervention. The T-ACE distinguished between
      heavier and lighter patterns of alcohol use in this sample. Moreover, it appeared
      that although the average quantity of alcohol consumed per drinking day was
      unchanged, the overall mean percentage of days drinking declined significantly
      from the time of enrollment to follow-up in all groups.

PMID- 16595358
TI  - Tramadol versus buprenorphine for the management of acute heroin withdrawal: a
      retrospective matched cohort controlled study.
AB  - Many medications have been used over the past thirty years for the treatment of
      opioid withdrawal, including propoxyphene, methadone, clonidine, parenteral
      buprenorphine, and, more recently, sublingual buprenorphine. Each has been found
      to have clinical strengths and limitations. Tramadol is a centrally acting
      synthetic analgesic with opiate activity primarily due to the binding of a
      metabolite to the micro receptor. Despite this micro receptor activity, tramadol
      appears to have low abuse potential and is a non-scheduled analgesic. The
      pharmacologic profile of tramadol makes it a candidate for opiate withdrawal
      treatment. A chart review was undertaken to retrospectively compare treatment
      outcomes of heroin-dependent patients when detoxified with parenteral
      buprenorphine (1996-1997) versus tramadol (1999-2000). Inclusion criteria for
      this study were heroin as drug of choice, current opioid physical dependence (ie,
      withdrawal symptoms), no current abuse of oral opioid analgesics, and no alcohol
      or benzodiazepine withdrawal symptoms. Patient cases that met inclusion criteria
      were group-matched between buprenorphine and tramadol on the basis of age, sex,
      and amount of heroin used (bags/day). Charts were audited for patient
      demographics, daily heroin use at admission, withdrawal symptoms, and discharge
      status. In total, 129 patient charts were reviewed, and 115 met all inclusion
      criteria and were group-matched (45 patients in the buprenorphine group, seventy
      in the tramadol group). There were no differences in demographics between the two
      groups of patients. Fifty-six percent of the buprenorphine group and 71% of the
      tramadol group completed detoxification; tramadol-treated patients had
      significantly higher average withdrawal symptoms when compared to the
      buprenorphine group and a greater reduction in withdrawal symptoms over time.
      Finally, the number of side effects was small and did not differ between the
      groups. The results of this study are consistent with previous pilot reports that
      indicated few clinical differences between parenteral buprenorphine and oral
      tramadol protocols when used in the management of acute heroin withdrawal. As a
      consequence, tramadol shows some promise as an opioid withdrawal management
      medication.

PMID- 16595359
TI  - Predictors of increased body mass index following cessation of smoking.
AB  - The objective of this study was to explore nicotine withdrawal symptoms as
      predictors of increased body mass index (BMI) after an attempt to quit or reduce
      tobacco smoking. The authors used a survey study, with a probability sample of
      4,075 18-64-year-old residents. The participation rate was 70.2%, which included
      1,545 current daily smokers. Follow-ups were carried out for current smokers
      after thirty and 36 months. The authors found that smokers who experienced
      increased appetite or weight gain (IAW) as a nicotine withdrawal symptom had a
      higher BMI than smokers without IAW. They concluded that IAW after quitting might
      be a specific determinant of the BMI increase following smoking cessation in a
      subgroup of smokers.

PMID- 16595360
TI  - Serotonin and suicidal behavior in patients with comorbid depression and
      alcoholism.

PMID- 16595363
TI  - Exploring the health care needs of women in abusive relationships in Japan.
AB  - In Japan, although there is increasing development of policy related to the
      problem of intimate partner violence (IPV), little attention has been paid to the
      health issues of battered women. We explored battered women's experiences in
      health care settings in Japan. Six women participated in focus group and
      individual interviews. We found that participants' injuries, both emotional and
      physical, stemming from IPV, were trivialized by health care providers. Women
      also were given little time to talk with health care providers. We discuss
      implications for health care practice, research, and policy.

PMID- 16595364
TI  - Chieko's story: giving voice to survivors of wife abuse.
AB  - Chieko's story relates in narrative form the childhood and early adult
      experiences of a Japanese woman who is learning to heal and rebuild her life
      after growing up in a violent home and ending an abusive marriage. This exemplar
      illustrates major processes and themes that emerged from a cross-cultural
      qualitative study of family violence. It also portrays universal aspects of this
      significant and pervasive health and social issue. This in-depth analysis and
      commentary on one woman's story that could have occurred almost anywhere uncovers
      hidden aspects contributing to the recidivism of this phenomenon. This story
      conveys hope for the many women and children who have no voice and for the
      clinicians who work with them.

PMID- 16595365
TI  - Postpartum mothers' disclosure of abuse, role, and conflict.
AB  - Experts evaluating evidence of the occurrence and effects of abuse before,
      during, and after pregnancy have called for research on the context within which
      violence occurs. This study elicited postpartum mothers' perceptions of roles and
      conflict in their abusive intimate relationships. Thirty newly delivered African
      , Anglo-, and Hispanic-American abused mothers consented to be interviewed. While
      ethnicity, cultural norms, and economic issues framed their descriptions, more
      than half (57%) described their relationships as not abusive even though they
      reported experiencing behaviors defined as abuse on standardized abuse screening
      instruments. Several women found ways to take care of themselves within the
      abusive relationship. The concerns that these diverse abused postpartum mothers
      expressed can serve as a foundation for the development of culturally sensitive
      interventions.

PMID- 16595366
TI  - Improving services for lesbian clients: what do domestic violence agencies need
      to do?
AB  - In her 2004 master's thesis Simpson identified that lesbian victims of domestic
      violence who are seeking services face systemic, institutional, and individual
      barriers. For this qualitative study, building on that work, we used in-depth
      interviews with six staff members who represented both a traditional domestic
      violence agency and a lesbian social service agency providing domestic violence
      services. The interviews revealed policy changes that might be made:
      institutional inclusion, assessment of language and literature, training and
      supervision, and institutional evaluation and quality assurance. These changes
      may improve the experiences of lesbian victims who are seeking services from
      domestic violence agencies. Each change, with specific examples provided, is
      discussed.

PMID- 16595367
TI  - Health care in Europe for women with genital mutilation.
AB  - The increasing number of immigrants from African countries practicing female
      genital mutilation (FGM) has raised concern in Europe. Health care professionals
      have developed three main responses: (1) technical guidelines for clinical
      management; (2) codes of conduct on quality of care; and (3) specialised health
      services for medical and psychological care and counselling. Much remains to be
      done, however, to ensure adequate care in Europe: (1) medico-legal/ethical
      discussions; (2) development of protocols to assist in making informed decisions;
      and (3) development of guidelines on counselling, communication strategies, and
      referral procedures. All agencies working in the field of FGM should be
      interlinked at the national level, in which members of the affected communities
      should be included. At the European level, a coordinated approach between all
      agencies should be developed.

PMID- 16595368
TI  - Modulation of human immunodeficiency virus infection by anticonvulsant drugs.
AB  - Patients with human immunodeficiency virus (HIV) infection often require
      treatment with anticonvulsants either for treatment of seizures or occasionally
      for pain control. In this study, the authors determined if the anticonvulsants
      phenytoin, carbamazepine, and valproate could modulate HIV replication. These
      drugs activated HIV replication in latently infected monocytic cells but not in
      latently infected lymphocytic cells at clinically relevant dosages. The
      activation in the monocytic cells was as a result of transactivation of HIV long
      terminal repeat (LTR) and could be seen at therapeutic dosages whereas no effect
      was seen on LTR activation in lymphocytic cells. When the drugs were used in
      conjunction with known transactivators of HIV LTR such as Tat and phorbol-12
      myristate-13-acetate (PMA), no additive or synergistic effect was noted. Although
      the clinical relevance of these observations needs to be determined, these
      observations may suggest that monitoring of cerebrospinal fluid (CSF) viral load
      maybe needed in HIV-infected patients treated with anticonvulsants, because HIV
      infected macrophages are important in mediating HIV dementia.

PMID- 16595369
TI  - A mutant deleted for most of the herpes simplex virus type 1 (HSV-1) UOL gene
      does not affect the spontaneous reactivation phenotype in rabbits.
AB  - The mechanisms involved in the herpes simplex virus type 1 (HSV-1) latency
      reactivation cycle are not fully understood. The latency-associated transcript
      (LAT) is the only HSV-1 RNA abundantly detected during neuronal latency. LAT
      plays a significant role in latency because LAT(-) mutants have a reduced
      reactivation phenotype. Several novel viral transcripts have been identified
      within the LAT locus, including UOL, which is located just upstream of LAT. The
      authors report here on a mutant, DeltaUOL, which has a 437-nucleotide deletion
      that deletes most of UOL. DeltaUOL replicated similarly to its wild-type parental
      McKrae HSV-1 strain in infected cells, the eyes, trigeminal ganglia, and brains
      of mice and rabbits. It was indistinguishable from wild-type virus as regards
      explant-induced reactivation in mice, and spontaneous reactivation in rabbits. In
      contrast, DeltaUOL was significantly less virulent in mice. Thus, UOL appears to
      be dispensable for the wild-type reactivation phenotype while appearing to play a
      role in neurovirulence in ocularly infected animals.

PMID- 16595370
TI  - Acute exposure to ethanol potentiates human immunodeficiency virus type 1 Tat
      induced Ca(2+) overload and neuronal death in cultured rat cortical neurons.
AB  - A significant number of human immunodeficiency virus type 1 (HIV-1)-infected
      patients are alcoholics. Either alcohol or HIV alone induces morphological and
      functional damage to the nervous system. HIV-1 Tat is a potent transcriptional
      activator of the viral promoter, with the ability to modulate a number of
      cellular regulatory circuits including apoptosis and to cause neuronal injury. To
      further evaluate the involvement of alcohol in neuronal injury, the authors
      examined the effect of ethanol on Tat-induced calcium responses in rat cerebral
      cortical neurons, using microfluorimetric calcium determination. HIV Tat protein
      (10 or 500 nM) elicited two types of calcium responses in cortical neurons: a
      fast-onset, short-lasting response and a slow-onset, sustained response. The
      responses were concentration-dependent and diminished in calcium-free saline. A
      short exposure to ethanol (50 mM) potentiated both types of calcium response,
      which was markedly decreased when the cells were pretreated with BAPTA-AM (20
      microM). In addition, an increase in the neurotoxic effect of Tat, which was
      assessed by trypan blue exclusion assay, was observed. The result led the authors
      to conclude that alcohol exposure significantly potentiates Tat-induced calcium
      overload and neuronal death.

PMID- 16595371
TI  - Platelet decline: an early predictive hematologic marker of simian
      immunodeficiency virus central nervous system disease.
AB  - As the prevalence of human immunodeficiency virus (HIV)-induced central nervous
      system (CNS) disease has increased with antiretroviral treatment, there is a
      critical need for identifying biomarkers that predict HIV CNS disease. To
      identify novel hematologic markers that precede and predict CNS disease, the
      authors examined longitudinal hematology data from 47 simian immunodeficiency
      virus (SIV)-infected macaques. This study demonstrated that the magnitude of
      decline in circulating platelet counts beginning at day 28 post infection, during
      asymptomatic SIV infection, predicted the eventual development of SIV
      encephalitis. Univariate analysis performed on platelet values obtained day 56
      post inoculation demonstrated that SIV-infected macaques with the greatest
      decline in platelet numbers were 18 times more likely to develop SIV CNS disease
      than SIV-infected animals with minimal to no decline in circulating platelet
      counts. Decline in platelet number was a more robust marker than decline in
      hemoglobin levels, a previously identified marker of HIV CNS disease. The
      identification of an association between decline in platelets and the development
      of encephalitis demonstrates that monitoring platelet decline in HIV-infected
      individuals may serve as a predictive marker for clinical progression to HIV
      induced CNS disease. Identifying those HIV-infected individuals at risk for CNS
      disease during asymptomatic stages of infection would promote early interventive,
      neuroprotective therapy to prevent neuronal damage and loss.

PMID- 16595372
TI  - Screening for human immunodeficiency virus (HIV) dementia in an HIV clade C
      infected population in India.
AB  - Although human immunodeficiency virus (HIV) clade C virus infects the largest
      populations worldwide, to date there are no prospective studies reported thus far
      to determine the incidence or prevalence of HIV dementia in this population. HIV
      clade C virus is a CCR5-tropic virus and thus predominantly infects macrophages,
      which are the key cells implicated in the pathogenesis of HIV dementia. However,
      HIV dementia has only rarely been reported in these populations. The authors thus
      used a recently developed International HIV Dementia Scale (IHDS) to screen a
      well-characterized cohort of HIV-infected discordant couples in Pune, India. 48
      HIV+ subjects with CD4 cell count <200 cells/mm(3) and 48 HIV- subjects were
      studied. The HIV+ subjects had significantly lower IHDS scores compared to the
      HIV- subjects. 35% of the HIV+ subjects and 15% of the HIV- subjects scored < 10
      on the IHDS. These observations suggest that the prevalence of HIV dementia may
      be higher in this population than previously reported. More importantly, it
      demonstrates that the IHDS can be used as a screening tool in the Indian
      population.

PMID- 16595373
TI  - JC virus in the Irish population: significant increase of genotype 2 in
      immunocompromised individuals.
AB  - The human polyomavirus JC virus (JCV) is ubiquitous and can be shed in the urine
      of more than 40% of the healthy population. Amplification and sequencing of JCV
      from urine has allowed a distinctive map of the distribution of JCV genotypes
      worldwide. To define the frequency of JCV urinary excretion and genotype
      distribution in Ireland, urines from 121 healthy individuals and from 94
      immunocompromised individuals (human immunodeficiency virus [HIV]-positive
      patients and rheumatoid arthritis patients) were collected. JCV DNA was detected
      by polymerase-chain reaction (PCR) with subsequent nucleotide sequencing of a
      fragment of the major capsid protein (VP1). JCV was detected in 20.7% of healthy
      individuals and was found significantly more often in the urine of HIV-positive
      patients (54.2%; P < .001) and rheumatoid arthritis patients (54.4%; P < .001).
      In healthy Irish individuals genotype 1 was the predominant genotype in 62.5%,
      followed by genotype 4 in 16.7% and genotype 2 in 12.5%. In contrast, genotype 2
      was significantly more often isolated from the urine of both HIV-positive
      patients (60%) and rheumatoid arthritis patients (54.4%; P < .01). The pattern of
      genotype distribution among healthy Irish individuals is in agreement with data
      reported from other European countries, whereas the overall level of JCV urinary
      excretion is lower. Previous studies have found genotype 2 significantly more
      often in cerebrospinal (CSF) samples of patients with progressive multifocal
      leukoencephalopathy (PML). Here the authors report an increased frequency of
      genotype 2 in urine samples of immunocompromised non-PML patients. This finding
      further underlines the hypothesis that there could be biologic differences
      between JCV genotypes.

PMID- 16595374
TI  - Use of human antigen presenting cell gene array profiling to examine the effect
      of human T-cell leukemia virus type 1 Tax on primary human dendritic cells.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is etiologically linked to adult T
      cell leukemia and a progressive demyelinating disorder termed HTLV-1-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP). One of the most striking
      features of the immune response in HAM/TSP centers on the expansion of HTLV-1
      specific CD8(+) cytotoxic T lymphocyte (CTL) compartment in the peripheral blood
      and cerebrospinal fluid. More than 90% of the HTLV-1-specific CTLs are directed
      against the viral Tax (11-19) peptide implying that Tax is available for immune
      recognition by antigen presenting cells, such as dendritic cells (DCs). DCs
      obtained from HAM/TSP patients have been shown to be infected with HTLV-1 and
      exhibit rapid maturation. Therefore, we hypothesized that presentation of Tax
      peptides by activated DCs to naIve CD8(+) T cells may play an important role in
      the induction of a Tax-specific CTL response and neurologic dysfunction. In this
      study, a pathway-specific antigen presenting cell gene array was used to study
      transcriptional changes induced by exposure of monocyte-derived DCs to
      extracellular HTLV-1 Tax protein. Approximately 100 genes were differentially
      expressed including genes encoding toll-like receptors, cell surface receptors,
      proteins involved in antigen uptake and presentation and adhesion molecules. The
      differential regulation of chemokines and cytokines characteristic of functional
      DC activation was also observed by the gene array analyses. Furthermore, the
      expression pattern of signal transduction genes was also significantly altered.
      These results have suggested that Tax-mediated DC gene regulation might play a
      critical role in cellular activation and the mechanisms resulting in HTLV-1
      induced disease.

PMID- 16595375
TI  - Neuronal pathways of viral invasion in mice after intranasal inoculation of
      pseudorabies virus PrV-9112C2 expressing bovine herpesvirus 1 glycoprotein B.
AB  - In contrast to wild-type Pseudorabies virus (PrV), which infects the central
      nervous system mainly via fibres of the trigeminal and autonomous nerves, the PrV
      mutant PrV-9112C2, deleted in glycoprotein B but expressing its bovine
      herpesvirus 1 (BHV-1) homologue, was shown to infect the swine central nervous
      system (CNS) via the olfactory route. In this study application of PrV-9112C2
      into the nose of mice resulted in CNS infection as described for wild-type PrV.
      These findings indicate that gB((BHV-1))-dependent changes in PrV's capability to
      infect swine olfactory sensory neurons (OSNs) are not prominent in mice and give
      evidence for viral entry receptors present in swine but not mice OSNs.

PMID- 16595376
TI  - Regulation of human endogenous retrovirus W protein expression by herpes simplex
      virus type 1: implications for multiple sclerosis.
AB  - The multiple sclerosis-associated retrovirus (MSRV), originally identified in
      cell cultures from patients with multiple sclerosis (MS), is closely related to
      the human endogenous retrovirus family W (HERV-W). Recently, HERV-W gag and env
      protein expression was demonstrated in MS lesions in situ. Here, the authors show
      that HERV-W gag and env proteins are induced by herpes simplex virus type 1 (HSV
      1) in neuronal and brain endothelial cells in vitro. The transactivation of HERV
      W proteins by HSV-1 could enhance their potential oligodendrotoxic and
      immunopathogenic effects, representing a mechanism by which HSV-1, and possibly
      also other herpesviruses associated with MS, may be linked to the pathogenesis of
      this disease.

PMID- 16595379
TI  - Mixed-effect models for evaluating multiple measures of atrazine exposure among
      custom applicators.
AB  - The exposure of custom (or commercial) applicators to the herbicide atrazine was
      measured in environmental (hand wash and dermal patch) and biological (urine and
      saliva) samples. Surrogate exposure data, such as amount of atrazine sprayed,
      were also collected. A systematic sampling design was used that included both
      spray and nonspray days. Fifteen applicators were sampled 5 to 7 days each during
      a 6-week spring spray season for a total of 89 sampled days. Mixed-effect
      regression modeling was used to examine the relationship among the surrogate,
      environmental, and biological atrazine exposure measures. Surrogate measures of
      atrazine application (either kg of atrazine sprayed or spray atrazine [yes/no])
      were significantly associated with increased levels of atrazine or atrazine
      equivalents (eq) in hand wash, thigh patch, 4-6 p.m. saliva, and 24-hour urine
      samples. Two days of spraying information (day of sampling and day before
      sampling) were needed to optimally estimate atrazine biomarkers in the biological
      samples, whereas only 1 day of spraying information (day of sampling) was needed
      to estimate atrazine levels in the environmental samples. Thigh and hand atrazine
      exposures were significantly associated with increased atrazine and atrazine eq.
      levels in the 4-6 p.m. saliva and 24-hour urine samples, respectively. Levels of
      4-6 p.m. salivary atrazine were also significantly associated with increased
      levels of 24-hour urinary atrazine eq. Atrazine levels in the 4-6 p.m. saliva
      samples tracked most closely with evening and next morning urinary atrazine eq.
      Number of days into the study at the time of sample collection predicted urinary
      and salivary atrazine levels independent of other fixed effects. These results
      indicate that either surrogate, environmental, or biological exposure measures
      can be used in appropriately specified models to estimate urinary and salivary
      atrazine biomarker levels.

PMID- 16595380
TI  - Estimating benzene exposure at a solvent parts washer.
AB  - A mathematical model is described for estimating benzene exposure at a parts
      washer using petroleum distillates solvent containing benzene. The basic
      assumptions are that the benzene mass emission rate exponentially decreases over
      time, and that the air above the parts washer basin to which a worker is exposed
      is part of a well-mixed air zone termed the near field (relative to the source
      location). Two previously conducted simulations of the parts washer process are
      described. A single 1-hour time-weighted average (TWA) benzene concentration was
      measured during Simulation #1, and two 4-hour TWA benzene concentrations were
      measured during Simulation #2. The initial benzene concentrations in the solvents
      were known, and the exponential loss rate constants were estimated from
      subsequent determinations of the benzene concentrations. Values for the
      interzonal airflow rate were estimated based on the conceptual geometry of the
      near field zone and sparse information on air speed near the parts washers.
      Minimum values for the room supply/exhaust air rate were estimated based on the
      room volumes and ventilation conditions. The modeled benzene concentrations were
      within a multiplicative range of one-half to twofold the measured concentrations.
      Uncertainty in a model estimate was quantified by Monte Carlo analysis; the
      distributions of model estimates exhibited coefficients of variation of
      approximately 40%. Issues related to uncertainty in exposure estimates made by
      mathematical modeling are discussed.

PMID- 16595382
TI  - Cultivating and maintaining effective action research partnerships: the DePaul
      and Oxford House collaborative.
AB  - In this paper, we review the result of research conducted in the context of a 13
      year collaborative partnership between DePaul University and a community-based,
      self-run, residential substance abuse recovery program called Oxford House. This
      collaborative effort highlights several examples of the research and action
      activities fostering a positive alliance that benefited both the research team
      and the Oxford House community. It also proposed practical guidelines for
      developing effective action research collaboratives that may be helpful to others
      who desire to cultivate and maintain similar mutually beneficial partnerships;
      including such processes as the development of trust, respecting the personal
      experiences of the community members and group, commitment to serving the
      community, validating findings with organization members, and accountability.

PMID- 16595378
TI  - Assessment of fungal contamination in moldy homes: comparison of different
      methods.
AB  - In an effort to better understand the relationship between different fungal
      sampling methods in the indoor environment, four methods were used to quantify
      mold contamination in 13 homes with visible mold. Swab, fungal spore source
      strength tester (FSSST), and air samples (total of 52 samples) were analyzed
      using both the microscopic (total spore count) and culture-based (CFU count)
      enumeration techniques. Settled dust samples were analyzed for culturable fungi
      only, as the microscopic enumeration was restricted by the masking effect. The
      relationships between the data obtained with the different sampling methods were
      examined using correlation analysis. Significant relationships were observed
      between the data obtained from swab and FSSST samples both by the total counting
      (r = 0.822, p < 0.05) and by the CFU counting (r = 0.935, p < 0.01). No
      relationships were observed between air and FSSST samples or air and settled dust
      samples. Percentage culturability of spores for each sampling method was also
      calculated and found to vary greatly for all three methods (swab: 0.03% to 63%,
      FSSST: 0.1% to > 100%, air: 0.7% to 79%). These findings confirm that reliance on
      one sampling or enumeration method for characterization of an indoor mold source
      might not provide an accurate estimate of fungal contamination of a
      microenvironment. Furthermore, FSSST sampling appears to be an effective
      measurement of a mold source in the field, providing an upper bound estimate of
      potential mold spore release into the indoor air. Because of the small sample
      size of this study, however, further research is needed to better understand the
      observed relationships in this study.

PMID- 16595383
TI  - Attitudes of a community members as a function of participatory research with
      Oxford Houses.
AB  - Citizen participation in research may include involvement in generating original
      ideas, planning appropriate designs, collecting data, and helping to implement
      interventions. Unfortunately, little is known about the attitudes of the
      community members who participate in such research processes. In the present
      exploratory study, a team of community members (4 men, 3 women; age > 30 years
      old) who were employed as investigator research associates to evaluate an
      innovative substance abuse recovery home were asked for their perspectives about
      their involvement in the research effort. Findings indicated that these community
      members felt their participation was a positive experience. Moreover, while their
      understanding and sense of participation in the research process increased, their
      identification and affiliation with their support organization was not reduced.
      Results imply that there is a need to better understand how citizen members of
      community organizations are affected by their involvement in the research
      process.

PMID- 16595385
TI  - This is my neighborhood: comparing United States and Australian Oxford House
      Neighborhoods.
AB  - The number of Oxford Houses, communal-living, mutual help settings for persons in
      recovery of alcohol and substance abuse, has spread across the United States and
      recently in and around Melbourne, Australia. In this study 55 US and 6 AU Houses
      were compared descriptively for their neighborhood characteristics. Across
      settings, there were greater similarities than significant differences in the
      locations. Results imply that Australian Oxford Houses are "safe and sober"
      settings for persons in recovery consistent with the original United States model
      in physical dwelling settings.

PMID- 16595384
TI  - Creating a home to promote recovery: the physical environments of Oxford House.
AB  - The interior and exterior physical characteristics of substance abuse recovery
      program dwellings (11 woman, 44 men) from three geographic sections of the United
      States were assessed at creating a "house-as-home" for residents. Although each
      house was independently governed and operated by residents, results indicated
      vast similarities among the interior characteristics, amenities, and structural
      aspects. These rented dwellings also had similar well-maintained exterior
      characteristics, despite their geographic locations. Follow-up interviews of
      former residents indicated that these house characteristics and amenities helped
      create a sense of home not found in traditional institutional facilities. Results
      suggested that residents of self-governed independently operated recovery houses
      may create and maintain safe and sober settings that elicit a sense of home among
      residents.

PMID- 16595386
TI  - The influence of policy on the differential expansion of male and female self-run
      recovery settings.
AB  - The present study used archival data to examine the differential growth among
      self-governed substance abuse recovery homes for men (N = 443) and women (N =
      125). The number of these homes increased dramatically across the U.S. from 1988
      1999 when state loan funds were made available to states and technical assistance
      was utilized by organizations developing the houses. State loan programs and the
      utilization of technical assistance, however, had the strongest impact on the
      expansion of women's houses compared to men's houses. The implications of these
      findings in relation to the scarcity of recovery options for women are discussed.

PMID- 16595387
TI  - Economic costs of Oxford House inpatient treatment and incarceration: a
      preliminary report.
AB  - The Oxford House model for substance abuse recovery has potential economic
      advantages associated with the low cost of opening up and maintaining the
      settings. In the present study, annual program costs per person were estimated
      for Oxford House based on federal loan information and data collected from Oxford
      House Inc. In addition, annual treatment and incarceration costs were
      approximated based on participant data prior to Oxford House residence in
      conjunction with normative costs for these settings. Societal costs associated
      with the Oxford House program were relatively low, whereas estimated costs
      associated with inpatient and incarceration history were high. The implications
      of these findings are discussed.

PMID- 16595388
TI  - Stress and coping: the roles of ethnicity and gender in substance abuse recovery.
AB  - This study investigated ethnic and gender differences in reported resource losses
      and gains for recovering substance abusers living in Oxford Houses (OH).
      Participants (n = 829) completed a version of Hobfoll's (1998) Conservation of
      Resources (COR) Evaluation. Results indicated significant individual differences
      in resources, based on gender, ethnicity, and the length of OH residential stay.
      Men reported fewer resource gains and losses than women. With respect to
      ethnicity, African-Americans reported greater gains and losses in resources than
      European-Americans. Individuals with less time in an OH also reported having
      experienced more losses in the past 3 months.

PMID- 16595389
TI  - Structural social support: impact on adult substance use and recovery attempts.
AB  - This study examined the structural social support of 132 men residing in a
      network of self-run, substance abuse recovery homes. The impact of different
      types of social relationships on individuals' substance use patterns and recovery
      attempts was investigated. Results suggest that varying relationship types (i.e.,
      parents, significant other, friends, children, coworkers) have significantly
      different influences on use and recovery. Additionally, each type of relationship
      had differential impacts on use versus recovery. Children were the sole
      relationship type that affected both substance use and recovery attempts in a
      positive nature, suggesting that children may have a beneficial impact on
      reducing.

PMID- 16595390
TI  - Medical care of individuals residing in substance abuse and recovery homes: an
      analysis of need and utilization.
AB  - The current study examined medical care need and utilization patterns among a
      substance abusing and recovering population (n = 876), investigating factors such
      as employment and drug use categories (e.g., pharmaceutical use, cocaine use,
      heroin use, alcohol use). It was found that those who were unemployed needed and
      utilized greater medical care than those who were employed. Results indicated
      that heroin, cocaine, and/or alcohol use was not predictive of medical care need
      or utilization, whereas pharmaceutical drug use was predictive of medical care
      need and utilization. Trauma and risky use of substances were not significant
      predictors of medical care need or utilization whereas the suicide severity
      composite was significant. Potential implications for misuse of medical services
      (e.g., to obtain pharmaceutical drugs of use) and federal medical care
      expenditure allocation are discussed.

PMID- 16595391
TI  - African American Oxford House residents: sources of abstinent social networks.
AB  - The current study found that African American residents of Oxford House (OH) used
      Narcotics Anonymous (NA) at high rates, and that both OH and NA strongly
      contributed to abstinent social networks. Having siblings and other family
      members in one's network predicted substance use among network members, whereas
      spouses, parents, and children did not have an effect on the rate of substance
      use. These findings suggest that OH and NA may be effective sources of abstinent
      social support for African Americans recovering from substance abuse. However,
      family members are well represented in the support networks of African Americans
      in OH.

PMID- 16595392
TI  - Children, women, and substance abuse: a look at recovery in a communal setting.
AB  - This study explored the sense of community among women (n = 21) and women with
      children (n = 30) living in Oxford Houses, with emphasis on how the presence of
      children might affect the household. Sense of community did not vary between
      participants with more or less than three months residence. Residents reported
      very high levels of satisfaction with the home, possibly because of a ceiling
      effect of little room for increases in their sense of community over time.
      Participants reported that they were getting along with the children in the home,
      that mothers could count on babysitting help, and that the children had a
      positive effect on the household and their own recovery process. This effect did
      not differ between mothers and non-mothers, suggesting that non-mothers might
      view the children in the home with a sense of responsibility and sensitivity
      comparable to that of the mothers. Implications are discussed.

PMID- 16595393
TI  - Women leadership in Oxford House: examining their strengths and challenges.
AB  - This study examined the perspectives and definition of leadership by women and
      mothers with children (n = 40) affiliated with Oxford Houses, a communal mutual
      help recovery setting. Participants were asked questions relating to their
      experiences living in an Oxford House including the strengths and challenges
      encountered and how leadership impacted the stability in their house. Results
      illustrated the value of female leadership and highlighted the characteristics
      deemed important for women leaders in Oxford House, as well as some differences
      between these women's perception of leadership and the standard definition of
      leadership. The implications of the findings and how they may be useful to
      women's and mothers' with children houses are discussed.

PMID- 16595394
TI  - Energy dissipation: new role for a carotenoid protein in cyanobacteria.

PMID- 16595395
TI  - Interorganellar communication: protein synthesis in organelles influences nuclear
      photosynthetic gene expression.

PMID- 16595396
TI  - Studies of abscisic acid perception finally flower.

PMID- 16595398
TI  - Community transformation through culturally competent nursing leadership:
      application of theory of culture care diversity and universality and tri
      dimensional leader effectiveness model.
AB  - Transcultural knowledge and competency have become a critical need for nurses to
      accommodate the global trends in cultural diversity and health care disparities.
      Today, nurses are increasingly taking on leadership roles in community settings.
      This article addresses the application of Leininger's culture care theory with
      the sunrise model and Hersey and Blanchard's tri-dimensional leader effectiveness
      model as potential collaborating theories for capacity building and community
      transformation from a global, transcultural nursing perspective. The two
      theories, used in collaboration, view the provision of competent leadership as
      the delivery of effective, culturally congruent nursing care in promoting health
      and health equity at the community level.

PMID- 16595397
TI  - Plant circadian rhythms.

PMID- 16595399
TI  - Nurses' concerns and practices with using interpreters in the care of Latino
      patients in the emergency department.
AB  - This phenomenological study aimed to describe nursing care of Latinos in the
      emergency department to determine how care is planned relative to the patient's
      ethnicity, including linguistic abilities. Unstructured interviews were conducted
      with 15 registered nurses from four hospitals in the Northwest. Interpreters play
      a pivotal role in nurses' practices. Nurses' skills with working with
      interpreters, interpreter availability, engagement, and accuracy enhance or
      impede effective care. Linguistic differences challenge effective care provision.
      Culturally competent care requires secure avenues of accurate communication.
      Administrators must provide nurses with resources that promote culturally
      competent care, including training with interpreters to facilitate effective
      communication.

PMID- 16595400
TI  - Health care seeking among Mexican American men.
AB  - This focused ethnography explored health care seeking beliefs and behaviors of
      Mexican American men living in south central Washington State. Data collection
      included interviews with 36 research participants living in the community,
      participant observation in the research setting, and examination of ethnographic
      documents and cultural artifacts. Four major themes were identified: the identity
      of manhood dictates health care seeking, health means being able to be a man by
      fulfilling cultural obligations, illness means not being able to be a man, and
      men seek health care when their manhood is threatened or impaired. Machismo, the
      cultural concept of manliness, persisted among men despite the level of
      acculturation and other factors. Women influenced men's health care seeking
      behaviors. To fulfill their obligations, men must stay healthy and seek care when
      needed. Knowing when and why men do not seek health care enables nurses to better
      understand and serve the Mexican American community.

PMID- 16595401
TI  - African American older adults coping with chronic health conditions.
AB  - This study's purpose is to identify strategies used by community-dwelling African
      American elders to cope with their chronic health conditions. A focus group study
      of 28 African American elders with multiple chronic conditions was conducted.
      Data collection occurred during the last 4 months of 2003. The five focus groups
      were audiotaped and transcribed verbatim. Content analysis was performed on the
      data to ascertain coping strategies employed to manage daily life with chronic
      conditions. Categories of coping strategies identified are (a) dealing with it,
      (b) engaging in life, (c) exercising, (d) seeking information, (e) relying on
      God, (f) changing dietary patterns, (g) medicating, (h) self-monitoring, and (i)
      self-advocacy. This study expands nurses' knowledge of the repertoire of coping
      strategies used by African American elders to ameliorate the effects of their
      chronic health conditions. Study findings will be valuable for planning
      intervention studies aimed at promoting successful coping.

PMID- 16595402
TI  - Beliefs and rituals in traditional birth attendant practice in Guatemala.
AB  - Childbearing women and infants in developing countries continue to experience
      unacceptably high rates of mortality and morbidity in spite of targeted
      initiatives to address the problem. The aim of this study was to identify the
      beliefs and rituals of traditional birth attendants (TBAs) in one indigenous
      Guatemalan community to better understand the cultural influences on perinatal
      care practices. Ethnographic methods were used to increase understanding of the
      practice of 10 Mayan TBAs. Three themes were constructed: sacred calling, sacred
      knowledge and sacred ritual.

PMID- 16595403
TI  - Learning the meaning of care: a case study in a geriatric home in Upper Egypt.
AB  - Geriatric care is a new phenomenon in Egypt. This study investigates how Egyptian
      caregivers experience their work and how they conceive its meaning. A qualitative
      case study in a geriatric home in Upper Egypt was conducted using structured
      interviews with 10 staff members and content analysis according to Mayring.
      Performing care required learning to overcome initial experiences of fear,
      disgust, and sexual taboo. Care was perceived as a laborious repetition. Its
      ideal form was described as a reaction to a demand combined with kind patience
      and a family-like relationship. Christian and female values allowed coping with
      experienced problems and alleviated conflicts between traditional gender roles
      and care of male residents. Traditional values helped to adapt to the
      requirements of providing care. Sexual taboos may reduce willingness to provide
      care, but traditional values may encourage caregivers.

PMID- 16595404
TI  - The level of cultural self-efficacy among a sample of Spanish nurses in
      southeastern Spain.
AB  - A collaborative study between faculty from the United States and Spain was
      undertaken to investigate levels of cultural self-efficacy among a sample of
      Spanish nursing students and nurses. Bandura's self-efficacy theory provided the
      conceptual framework for this descriptive study. The Spanish version of the
      Cultural Self-Efficacy Scale (CSES-S) was translated from the original developed
      by Bernal and Froman using the back-translation technique recommended by Brislin.
      The CSES-S was administered to 113 Spanish nurses and students. Alpha coefficient
      results for the CSES-S ranged from .90 to .95. Low to neutral levels of
      confidence in caring for four ethnic groups were found. Regression analyses
      showed significant relationships between cultural exposure and cultural self
      efficacy for the practicing nurses. Results will assist this collaborative
      transcultural nursing research effort between the United States and Spain to
      develop and implement programs and experiences to increase cultural self-efficacy
      among Spanish nurses and improve care provided to Spain's diverse population.

PMID- 16595405
TI  - Perceptions of graduating nursing students regarding life experiences that
      promote culturally competent care.
AB  - This article describes a qualitative study that explored the perceptions of
      graduating students from a northeast baccalaureate nursing program regarding
      their life experiences with cultural diversity. Thirteen students were
      interviewed using an interview guide, and interviews were recorded on audiotape.
      Information obtained included participants' cultural heritage, life experiences
      before entering a nursing program, educational and clinical experiences in the
      nursing program, knowledge about cultural competence, and the students'
      reflections on their ability to provide culturally competent care. Primarily
      qualitative methods were used to gather and analyze data. This article focuses on
      one of the major themes that emerged: defining life experiences related to
      cultural diversity. Data were reanalyzed focusing on this theme, and three life
      patterns emerged: positive, neutral, and conflicted. These patterns affected the
      students' interest and desire to provide culturally competent care. Implications
      for further research and nursing education are discussed.

PMID- 16595406
TI  - Strategies for developing cultural competency in an RN-BSN program.
AB  - It is crucial for nurses to acquire skills and a knowledge base to care for
      increasingly diverse cultural populations. Many nurses returning to school did
      not receive theoretical information relative to culture. This article describes
      some of the teaching strategies utilized in the RN-BSN program at Bethel College
      in Mishawaka, Indiana. This "how we did it" discussion is presented to provide
      ideas for teaching strategies that may be used to promote attainment of a program
      outcome related to cultural sensitivity and competency.

PMID- 16595407
TI  - The role of the African traditional healer in women's health.
AB  - Traditional healers provide an important link between the rural people of Africa
      and primary health care. The purpose of this article is to review more recent
      literature and contemporary practices related to the role of the traditional
      healer in Africa and the move toward collaboration with an introduction of
      Western-style medicine and health care, especially for women. African women,
      particularly older ones in rural communities, utilize the traditional healer's
      timeless and ancient caregiving when faced with symptoms of mental and physical
      illness. The concept of training traditional healers and medical personnel to
      deliver traditional and Western health care to communities requires further
      consideration and a plan of implementation.

PMID- 16595408
TI  - A guide for visiting clinicians to Guatemala: common presenting symptoms and
      treatment.
AB  - For volunteer clinicians from North America and Europe, treating patients for the
      first time in remote areas of Guatemala can be a challenge. Radiology and
      laboratory facilities are usually lacking, and the cultural and linguistic
      barriers are huge. This article provides clinicians working in Guatemala with a
      description and ranking of the most common presenting complaints, as determined
      from a chart review of 1,500 patients. Unfamiliar diagnoses, empiric treatment,
      and pertinent cultural factors, including the fading but still-present hot-cold
      paradigm, are also included.

PMID- 16595409
TI  - What is the empirical basis for paying for quality in health care?
AB  - Despite more than a decade of bench-marking and public reporting of quality
      problems in the health care sector, changes in medical practice have been slow to
      materialize. To accelerate quality improvement, many private and public payers
      have begun to offer financial incentives to physicians and hospitals based on
      their performance on clinical and service quality measures. The authors review
      the empirical literature on paying for quality in health care and comparable
      interventions in other sectors. They find little evidence to support the
      effectiveness of paying for quality. The absence of findings for an effect may be
      attributable to the small size of the bonuses studied and the fact that payers
      often accounted for only a fraction of the targeted provider's panel. Even in non
      health settings, however, where the institutional features are more favorable to
      a positive impact, the literature contains mixed results on the effectiveness of
      analogous pay-for-performance schemes.

PMID- 16595410
TI  - Indices for continuity of care: a systematic review of the literature.
AB  - This article systematically reviews published literature on different continuity
      of care (COC) indices that assess the physician-patient relationship and the
      applicability of such indices to pediatric and chronic-disease patient
      populations. Frequency and visit type may vary for pediatric and chronically ill
      patients versus healthy adult patients. Two investigators independently examined
      5,070 candidate articles and identified 246 articles related to COC. Forty-four
      articles were identified that include 32 different indices used to measure COC.
      Indices were classified into those that calculated COC primarily based on
      duration of provider relationship (n=2), density of visits (n=17), dispersion of
      providers (n=8), sequence of providers (n=1), or subjective estimates (n=4). The
      diversity of COC indices reflect differences in how this measure is
      conceptualized. No index takes into account the visit type. A unique index that
      reflects continuity in the physician patient relationship for pediatric and
      chronic disease populations is needed.

PMID- 16595411
TI  - Bureaucratic policy making on trial: medicaid nursing facility reimbursement,
      1988-1998.
AB  - Few systematically assess the determinants of Medicaid nursing facility
      reimbursement. Consequently, this article examines what factors influence program
      administrators'decisions regarding nursing facility cost report data-the basic
      information states use to establish payment. Whereas elected officials focus
      primarily on how much is spent on nursing homes, state Medicaid officials assume
      primary responsibility for the esoteric and highly technical dimensions that help
      make spending goals a reality. Findings indicate that the federal government
      influenced state policy by enabling provider litigation under the Boren
      Amendment. They also indicate that program administrators responded rationally to
      fiscal and economic concerns, and that states with stronger administrative
      capacity were better able to overcome obstacles to sustaining desired policies.
      Although results reveal that states with more powerful nursing home lobbies
      tended to implement more generous systems, they fail to reveal significant
      associations between cost report year and lobbying activity on behalf of the
      elderly.

PMID- 16595412
TI  - Self-reported utilization of health care services: improving measurement and
      accuracy.
AB  - Self-report is often used to estimate health care utilization. However, the
      accuracy of such data is of paramount concern. The authors conducted a systematic
      review of 42 studies that evaluated the accuracy of self-report utilization data,
      where utilization was defined as a visit to a clinical provider or entity. They
      also present a broad conceptual model that identifies major issues to consider
      when collecting, analyzing, and reporting such data. The results show that self
      report data are of variable accuracy. Factors that affect accuracy include (1)
      sample population and cognitive abilities, (2) recall time frame, (3) type of
      utilization, (4) utilization frequency, (5) questionnaire design, (6) mode of
      data collection, and (7) memory aids and probes.

PMID- 16595413
TI  - Validating CPT typical times for Medicare office evaluation and management (E/M)
      services.
AB  - Every 5 years, the federal government reviews the Medicare Fee Schedule for
      changes in the work effort physicians personally devote to office visits. Using
      physician face-to-face times reported in the Centers for Disease Control and
      Prevention's National Ambulatory Care Survey (NAMCS), guideline office visit
      times associated with the 1997-1998 mix of Medicare claims averaged 9 percent
      longer versus NAMCS; Medicare billed visits with new patients were 32 percent
      longer. Surgeons and dermatologists had the largest discrepancies in Medicare
      versus NAMCS times. If CPT guideline times currently in use are now overstated,
      then intraservice work effort is likely overstated given the high correlation of
      time with work effort, and Medicare payment levels need to be reduced. Upcoding
      visit content to higher paid CPT visit codes may also explain seemingly longer
      Medicare billed times and call for payment reductions as well.

PMID- 16595416
TI  - For the record: journal publishers and the arms trade.

PMID- 16595417
TI  - Severity of injury measures and descriptive epidemiology.

PMID- 16595418
TI  - Politics can be deadly.

PMID- 16595419
TI  - Would society pay more attention to injuries if the injury control community paid
      more attention to risk communication science?

PMID- 16595420
TI  - Effectiveness of bicycle helmet legislation to increase helmet use: a systematic
      review.
AB  - BACKGROUND: Head injuries related to bicycle use are common and can be serious.
      They can be prevented or reduced in severity with helmet use; however, education
      has resulted in modest helmet use in most developed countries. Helmet legislation
      has been proposed as a method to increase helmet wearing; while this social
      intervention is thought to be effective, no systematic review has been performed.
      OBJECTIVES: This review evaluates the scientific evidence for helmet use
      following legislation to identify the effectiveness of legislative interventions
      to increase bicycle helmet use among all age groups. SEARCH STRATEGY:
      Comprehensive searches of CENTRAL, MEDLINE, EMBASE, CINAHL, Web of Science,
      British Education Index, LILACS Database, TRIS (Transport Research Information
      Service), the grey literature, reference lists, and communication with authors
      was performed to identify eligible studies. SELECTION CRITERIA: Eligible studies
      for this review were community based investigations including cohort studies,
      controlled before-after studies, interrupted time series studies, non-equivalent
      control group studies Data collection and analysis: Two reviewers extracted the
      data regarding the percentage of helmet use before and after legislation from
      each study. Individual and pooled odds ratios were calculated along with 95%
      confidence intervals. MAIN RESULTS: Out of 86 prescreened articles, 25 were
      potentially relevant to the topic and 11 were finally included in the review. Of
      11 studies, eight were published articles, two were published reports, and one
      was an unpublished article. One additional survey was incorporated following
      personal communication with the author. While the baseline rate of helmet use
      among these studies varied between 4% and 59%, after legislation this range
      changed to 37% and 91%. Helmet wearing proportions increased less than 10% in one
      study, 10-30% in four studies, and more than 30% in seven studies. While the
      effectiveness of bicycle helmet legislation varied (n = 11 studies; OR range: 1.2
      22), all studies demonstrated higher proportions of helmet use following
      legislation, particularly when the law was targeted to a specific age group.
      CONCLUSIONS: Legislation increased helmet use among cyclists, particularly
      younger age groups and those with low pre-intervention helmet wearing
      proportions. These results support legislative interventions in populations
      without helmet legislation.

PMID- 16595421
TI  - Passenger seating position and the risk of passenger death in traffic crashes: a
      matched cohort study.
AB  - OBJECTIVE: To estimate the association of passenger seating position with the
      risk of death for passengers in traffic crashes. DESIGN, SETTING, PARTICIPANTS:
      Matched cohort analysis of data from the National Highway Traffic Safety
      Administration Fatality Analysis Reporting System regarding 56 644 passengers in
      23 308 passenger cars, light trucks, vans, and sport utility vehicles that
      crashed during 1990-2001. MAIN OUTCOME MEASURE: The adjusted risk ratio (aRR) for
      death of a rear seat passenger compared with a front seat passenger within 30
      days of a crash. RESULTS: The aRR for all passengers in the rear seat in a crash
      was 0.79 (95% CI 0.77 to 0.82). This estimate varied by age, restraint use, and
      the presence of a front passenger airbag (p<0.001). For restrained passengers in
      cars with a front passenger airbag, the aRR was 0.62 (95% CI 0.48 to 0.81) for
      children 0-12 years, 0.96 (95% CI 0.88 to 1.06) for passengers 13-29 years, 1.03
      (95% CI 0.93 to 1.15) for passengers 30-59 years, and 1.06 (95% CI 0.90 to 1.26)
      for passengers 60 years or older. The rear seat was associated with more
      protection in cars without front airbags and more protection for unrestrained
      passengers compared with restrained passengers. CONCLUSIONS: Previous studies
      have reported that the rear seat was safer for persons of all ages; thus seating
      a young child in the rear has often meant that older children and adults had to
      assume an increased risk of death by sitting in the front. These results suggest
      that when front passenger airbags are present and passengers are restrained,
      putting adults in front and children in back enhances child safety without
      sacrificing adult safety.

PMID- 16595422
TI  - Associations between risk behavior and injury and the protective roles of social
      environments: an analysis of 7235 Canadian school children.
AB  - OBJECTIVE: The social etiology of adolescent injury remains poorly understood.
      The Population Health Framework suggests that the etiology of adolescent injury
      involves interactions between individual risk factors and the natures of
      adolescent environments. The purpose of this study was to apply this framework to
      examination of relationships between adolescent risk taking and injury, and the
      potential modifying effects of supportive home and school environments. METHODS:
      The analysis was conducted in a representative sample of 7235 males and females
      (10-16 years old) from Canada. Results were based on records from the 2001/02
      World Health Organization Health Behaviour in School-Aged Children Survey.
      Individual items and factor analytically derived scales were used to describe and
      then model injury outcomes, risk behaviors, perceived home, and school climates,
      and the relationships between these variables in a theory driven etiological
      analysis. RESULTS: Adolescents with supportive home and school environments
      experienced lower relative odds of engagement in risk taking behavior and lower
      relative odds of injury. Gradients were observed between the extent of adolescent
      risk taking and the occurrence of injury. Interactions were not observed between
      risk taking behavior, perceived support in home and school climates, and injury.
      CONCLUSIONS: Risk taking is common among adolescents and plays a role in the
      etiology of injury. Supportive social climates clearly protect adolescents from
      engaging in these behaviors, and also the occurrence of some forms of injury.
      However, once an adolescent chooses to engage in risk taking behaviour, a
      supportive environment may not protect them from injury.

PMID- 16595423
TI  - A prospective cohort study of health outcomes following whiplash associated
      disorders in an Australian population.
AB  - OBJECTIVE: To define health outcomes of whiplash associated disorders (WAD) at
      three months, six months, and two years after injury and to examine predictors of
      these outcomes. DESIGN: Prospective cohort study. SETTING: New South Wales,
      Australia. SUBJECTS: People with compensable motor crash injuries who reported
      whiplash as one of their injuries. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      Functional Rating Index (FRI), Short Form 36 (SF-36) at three months, six months,
      and two years after injury, ascertained by telephone interview. RESULTS: At three
      months, 33.6% of the cohort was recovered (as defined by FRI<or=25), increasing
      marginally at six months (38.9% recovered), but more significantly at two years
      (51.7% recovered, p = 0.001). The mean physical component score of the SF-36
      improved at each time point (p = 0.002), while the mean mental component score
      did not (p = 0.59). Predictors of recovery at two years (as defined by global
      perceived effect) included a lower FRI index at baseline (p = 0.001) and closure
      of the claim at two years (p = 0.02). CONCLUSION: Whiplash injury had a large
      effect on the health of this Australian cohort of whiplash sufferers, with only
      50% of the cohort recovered at two years. Physical measures of health appear to
      improve over time, whereas mental measures of health did not. Despite this, this
      cohort is largely able to participate in activities and work at two years.
      Prevention of chronic disability may lie with concentration of resources to those
      who score highly on the FRI at baseline. In addition, chronic psychological ill
      health may be prevented by directing treatment to those with poor scores on
      sensitive measures of psychological ill health at baseline.

PMID- 16595424
TI  - Child passenger safety for inner-city Latinos: new approaches from the community.
AB  - OBJECTIVE: Motor vehicle crashes injuries, the leading cause of death for Latino
      children in the United States, can be reduced by the correct use of child safety
      seats. This study evaluated the ability of a community health worker education
      program to improve proper child safety seat usage in urban low income Latino
      families. METHODS: At a series of check events, proper child safety seat usage in
      families who had received an education intervention was compared with similar
      families who had not. The education intervention, provided by Latino community
      health workers trained as child passenger safety technicians, used videos and an
      office demonstrator. Members of the target community initiated the study and
      participated in its subsequent design and implementation. RESULTS: The families
      that participated in the study were primarily Mexican with low income, education,
      and acculturation levels. Forty six rear facing and 44 forward facing child
      safety seats were checked. Families exposed to the intervention were more likely
      to have their child's seat within the manufacturer's recommended weight/height
      range, their child facing the correct direction, the harness straps positioned
      properly, to have not been in a crash, the harness straps snug, the harness
      retainer clip used correctly, the seat belt routed correctly, and the seat belt
      locked. CONCLUSIONS: Exposure to an educational intervention provided by
      community health workers trained as child passenger safety technicians was
      associated with child safety seats being used more properly than seats of
      families not exposed to the intervention in an urban low income Latino community.

PMID- 16595425
TI  - Young people and work injuries: an examination of jurisdictional variation within
      Canada.
AB  - OBJECTIVE: The purpose of this study was to identify risk factors of work
      injuries among Canadian adolescents and young adults and to examine provincial
      differences in work injury rates. METHODS: Information on work and injuries were
      obtained from a representative sample of 14 541 Canadians aged 15-24 years.
      Respondents reported medically attended, work related injuries in the past 12
      months, work hours, and type of occupation. A multivariate logistic regression on
      likelihood of work injury included demographic and work variables, as well as
      province of residence. RESULTS: Even when factors expected to vary by province
      such as occupation were statistically controlled, Saskatchewan youth were about
      twice as likely to be injured at work compared to Ontario youth. Type of job was
      a major correlate of injury risk, with all jobs showing higher risk than
      administrative clerical jobs. Even with type of job controlled, visible
      minorities, students, and 15-17 year olds had a reduced likelihood of work injury
      than their counterparts. CONCLUSIONS: Many young Canadians sustain work injuries
      that have clear medical costs and potential long term health consequences.
      Individual level explanations for youth's increased risk for workplace injuries
      (for example, inexperience or developmental factors) need to be supplemented with
      a better understanding of the broader social, economic, and political factors
      across jurisdictions.

PMID- 16595426
TI  - Estimating injury severity using the Barell matrix.
AB  - OBJECTIVE: To determine whether the Barell matrix (Inj Prev 2002;8:91-6) could
      effectively categorize injuries by severity. METHODS: Injury diagnoses of cases
      in the 2002 US Nationwide Inpatient Sample were classified according to the
      Barell matrix. For each cell of the matrix, the authors used ICDMAP-90 to
      determine the predominant Abbreviated Injury Score (AIS) and body region, and
      calculated the weighted proportion surviving (bPScell) among patients with any
      diagnosis in that cell. These findings were used to estimate maximum AIS
      (bAISmax), ISS (bISS), and the minimum or product of bPScell (bPSmin, bPSprod)
      for injured patients in the 1996-2000 US National Hospital Discharge Surveys.
      Case survival was determined for different scores, and outcome models using age,
      sex, comorbidity, mechanism, and bISS or bPSmin were compared to models using ISS
      calculated from ICDMAP-90 (mISS) or using ICISS. RESULTS: Case survival decreased
      with increasing bAISmax or bISS; survival was closely approximated by bPSmin, and
      also increased monotonically with bPSprod. Outcome models using bISS or bPSmin
      were similar to those using mISS or ICISS. An Abbreviated Barell Categorization,
      with only four groups, was also effective. CONCLUSION: Barell matrix
      categorization of administrative data allows severity scoring similar to that
      obtainable with ICDMAP-90 or ICISS.

PMID- 16595427
TI  - A comparison of information on motor vehicle crashes as reported by written or
      telephone interviews.
AB  - OBJECTIVE: To compare information about traffic crash injuries and kilometers
      driven reported in a written questionnaire with information reported in a
      telephone interview. DESIGN: Telephone and paper surveys. SETTING: The
      Seguimiento Universidad de Navarra (SUN, University of Navarra Follow-up) study,
      in Spain. The SUN study is an open enrollment cohort study with 17 000 enrolled
      graduates followed through biennial mailed questionnaires. SUBJECTS: A sample of
      542 individuals from the SUN study participants. MAIN OUTCOME MEASURE: Agreement
      on information about traffic crash injuries and mileage driven in a mailed
      questionnaire and a telephone survey. RESULTS: Participation was 90.4%.
      Considering the phone survey as the gold standard, data on traffic crash injuries
      in the mailed questionnaire had 83% sensitivity (95% CI 77% to 89%), 77%
      specificity (95% CI 71% to 82%), 74% positive predictive value (95% CI 67% to
      80%), and 89% negative predictive value (95% CI 83% to 93%). Agreement beyond
      chance, measured by the kappa statistic, was 0.63 (95% CI 0.56 to 0.70).
      Correlation between questionnaire and telephone surveys and kilometers driven on
      average during a year assessed by the intraclass correlation coefficient was 0.64
      (95% CI 0.57 to 0.70), p<0.001. CONCLUSIONS: Information on sustained traffic
      crash injuries and traveled mileage over the previous two years as reported
      through mailed questionnaires in a highly educated population could be used in
      the study of associations between traffic crash injuries and a variety of risk
      factors.

PMID- 16595428
TI  - Ascertainment of intimate partner violence using two abuse measurement
      frameworks.
AB  - OBJECTIVE: To estimate prevalence of intimate partner violence (IPV) according to
      two abuse ascertainment tools, and agreement between the tools. METHODS: 2504
      women randomly selected from a health maintenance organization were asked about
      IPV exposure in their most recent intimate relationship using five questions on
      physical and sexual abuse, and fear due to partner's threats and controlling
      behavior from the Behavioral Risk Factor Surveillance Survey (BRFSS) and 10
      questions from the Women's Experience with Battering (WEB) scale. IPV prevalence
      was estimated according to the BRFSS and WEB, and the proportion of women who
      were WEB+/BRFSS+, WEB-/BRFSS-, WEB-/BRFSS+, and WEB+/BRFSS-. RESULTS: In their
      most recent relationship, 14.7% of women reported abuse of any type on the BRFSS
      versus 7.0% on the WEB scale. In direct comparisons of the WEB and BRFSS
      questions, a higher percentage of abused women reported any IPV on the five BRFSS
      questions (88.4%) compared to the 10 WEB questions (42.0%). However, both the
      BRFSS and WEB identified some women as abused that would have been missed by the
      other instrument. CONCLUSIONS: Intimate partner violence prevalence depends on
      how women are asked about abuse. Resources permitting, more than one abuse
      ascertainment strategy (for example, both the BRFSS and WEB questions) should be
      tried in order to broadly identify as many women as possible who interpret
      themselves as abused.

PMID- 16595429
TI  - Road traffic casualties: understanding the night-time death toll.
AB  - A disproportionate number of fatal injuries occur after dark. The paper presents
      some statistics of road traffic injuries in a novel way which suggests that low
      luminance plays a major role in this effect. A sound physiological explanation
      for this is advanced based on the poor temporal characteristics of rod
      photoreceptors. It is argued that processing information based on low luminance,
      low contrast targets is much slower than that for high contrast bright targets.
      To test the idea, simple visual reaction times were measured under typical low
      visibility conditions encountered on non-lit roads and were found to be
      substantially longer than under optimal conditions. It is shown that longer
      reaction times translate into significantly increased stopping distances. This
      important point has received insufficient attention in the road safety
      literature, by the Highways Agency, the police, injury prevention officials, and
      the UK Highway Code.

PMID- 16595431
TI  - Incidence of trampoline related pediatric fractures in a large district general
      hospital in the United Kingdom: lessons to be learnt.
AB  - AIM: To test the observation that the incidence of trampoline related pediatric
      fractures is increasing-both nationally and in a large district general hospital.
      METHOD: A retrospective analysis was undertaken of patient records establishing
      mechanism of injury of pediatric fractures over three consecutive summers from
      2000-03. Theatre records of fractures treated operatively were used as the
      initial data source. RESULTS: A statistically significant increase in trampoline
      related injuries was discovered. This reflects the rising incidence of injuries
      from national data and furthermore corresponds to the growing popularity of
      domestic use trampolines in the UK. CONCLUSION: The incidence of injuries is
      increasing. There are lessons to be learnt from existing work from countries
      where trampoline prevalence has been greater for longer. The authors recommend
      various safety measures that may reduce children's injuries.

PMID- 16595430
TI  - The spectrum of intoxication and poisonings among adolescents: surveillance in an
      urban population.
AB  - AIM: Among adolescents, poisoning is a leading cause of injury mortality in the
      United States. This study describes the epidemiology of poisonings, intoxication,
      and maladaptive effects of drugs among adolescents age 10-19 years in a large
      city. METHODS: An injury surveillance system used records at seven hospitals,
      medical examiner records, and vital records over a two year period. RESULTS: Of
      633 cases (618 injuries/100 000/year), 6% were unintentional, 36% self-inflicted,
      41% alcohol intoxication, and 15% maladaptive effects of drugs. Alcohol was
      involved in 45% of cases, 23% illegal drugs, 23% non-prescription drugs, 19%
      prescription drugs; 19% involved more than one substance. Hospitalization was
      required in 20%; 8% transferred to another hospital; one died from intoxication.
      The authors found high rates of self-inflicted poisoning, intoxication, and
      maladaptive effects of drugs among this urban population. CONCLUSION: The study
      highlights the need to broadly define poisonings among adolescents and the
      challenge of assessing intent in some cases.

PMID- 16595432
TI  - Climate change control and injury prevention: more win-win solutions.

PMID- 16595433
TI  - Resources for terror and road injury prevention.

PMID- 16595434
TI  - Intervertebral disc degeneration. Proceedings of a workshop organized by the
      American Academy of Orthopaedic Surgeons, the National Institutes of Health, and
      the Orthopaedic Research Society. September 15-18, 2005.

PMID- 16595435
TI  - Lumbar disc degeneration: epidemiology and genetics.
AB  - Research conducted over the past decade has led to a dramatic shift in the
      understanding of disc degeneration and its etiology. Previously, heavy physical
      loading-often associated with occupation-was the main suspected risk factor for
      disc degeneration, which was commonly viewed as a wear-and-tear phenomenon
      exacerbated by the precarious nutritional status of the disc. However, results of
      studies on twins suggest that physical loading specific to occupation and sport
      plays a relatively minor role in disc degeneration. Recent research indicates
      that heredity has a dominant role in disc degeneration, which would explain the
      variance of up to 74% seen in adult populations that have been studied to date.
      Since 1998, genetic influences have been confirmed by the identification of
      several gene forms associated with disc degeneration. This research is paving the
      way for a better understanding of the biologic mechanisms through which disc
      degeneration occurs, including specific interactions between genes and
      environment. Research into disc degeneration and genetics has become more limited
      by phenotypes or definitions and measures of disc degeneration than by DNA
      analysis. Standardized, universally accepted definitions of disc degeneration are
      lacking, in part due to limited knowledge of the process. The measurements that
      are selected depend on the method used to evaluate the disc and are often
      qualitative ordinal rating scales, lacking in precision. Although it is generally
      agreed that disc degeneration is common, the prevalence of specific findings is
      unclear. A review of the epidemiology of disc degeneration reveals wide-ranging
      prevalence estimates for various signs of disc degeneration in samples of the
      general population and in patients with back symptoms. The extreme variations in
      prevalence rates are likely largely due to inconsistencies in the definitions and
      measurements of disc degeneration. Such inconsistencies and inaccuracies impede
      epidemiologic research on disc degeneration.

PMID- 16595436
TI  - Histology and pathology of the human intervertebral disc.
AB  - The intervertebral disc is a highly organized matrix laid down by relatively few
      cells in a specific manner. The central gelatinous nucleus pulposus is contained
      within the more collagenous anulus fibrosus laterally and the cartilage end
      plates inferiorly and superiorly. The anulus consists of concentric rings or
      lamellae, with fibers in the outer lamellae continuing into the longitudinal
      ligaments and vertebral bodies. This arrangement allows the discs to facilitate
      movement and flexibility within what would be an otherwise rigid spine. At birth,
      the human disc has some vascular supply within both the cartilage end plates and
      the anulus fibrosus, but these vessels soon recede, leaving the disc with little
      direct blood supply in the healthy adult. With increasing age, water is lost from
      the matrix, and the proteoglycan content also changes and diminishes. The disc
      particularly the nucleus-becomes less gelatinous and more fibrous, and cracks and
      fissures eventually form. More blood vessels begin to grow into the disc from the
      outer areas of the anulus. There is an increase in cell proliferation and
      formation of cell clusters as well as an increase in cell death. The cartilage
      end plate undergoes thinning, altered cell density, formation of fissures, and
      sclerosis of the subchondral bone. These changes are similar to those seen in
      degenerative disc disease, causing discussion as to whether aging and
      degeneration are separate processes or the same process occurring over a
      different timescale. Additional disorders involving the intervertebral disc can
      demonstrate other changes in morphology. Discs from patients with spinal
      deformities such as scoliosis have ectopic calcification in the cartilage end
      plate and sometimes in the disc itself. Cells in these discs and cells from
      patients with spondylolisthesis have been found to have very long cell processes.
      Cells in herniated discs appear to have a higher degree of cellular senescence
      than cells in nonherniated discs and produce a greater abundance of matrix
      metalloproteinases. The role that abnormalities play in the etiopathogenesis of
      different disorders is not always clear. Disorders may be caused by a genetic
      predisposition or a tissue response to an insult or altered mechanical
      environment. Whatever the initial cause, a change in the morphology of the tissue
      is likely to alter the physiologic and mechanical functioning of the tissue.

PMID- 16595437
TI  - Imaging intervertebral disc degeneration.
AB  - Magnetic resonance imaging provides excellent anatomic detail of spinal tissues,
      but fails to provide the type of information that permits a definitive diagnosis
      in many patients with back pain. New imaging strategies that can be applied to
      the study of intervertebral disc degeneration include diffusion-weighted imaging,
      magnetic resonance imaging, diffusion tensor imaging, magnetic resonance
      spectroscopy, functional magnetic resonance imaging, dynamic computed tomography
      and magnetic resonance imaging, and T2 relaxometry. With dynamic imaging, the
      relative motions of normal and degenerated lumbar motion segments can be
      evaluated noninvasively. With further evaluation of the technique, hypermobile
      segments may be distinguishable from those with normal relative motion. T2
      measurements obtained by T2 relaxometry appear to have important advantages with
      regard to spinal imaging because this modality provides a continuous and
      objective measure of the content of free water in the disc, which decreases with
      aging and degeneration. Anatomic imaging of the spine is highly accurate in the
      evaluation of nonmechanical causes of back pain and less beneficial in the
      evaluation of back pain that is due to mechanical causes. The development of
      functional imaging strategies of the spine will likely improve the management of
      patients with back pain. This article outlines the current magnetic resonance
      imaging protocols for intervertebral disc degeneration, indicates deficiencies in
      current imaging, and describes functional imaging strategies for the spine that
      will likely improve the evaluation of patients with back pain. It also reviews
      recent published articles on magnetic resonance imaging and computed tomographic
      imaging of the spine and details the results of studies that have explored the
      future potential of spine imaging.

PMID- 16595438
TI  - Lumbar disc disorders and low-back pain: socioeconomic factors and consequences.
AB  - Socioeconomic factors are important risk factors for lumbar pain and disability.
      The total costs of low-back pain in the United States exceed $100 billion per
      year. Two-thirds of these costs are indirect, due to lost wages and reduced
      productivity. Each year, the fewer than 5% of the patients who have an episode of
      low-back pain account for 75% of the total costs. Because indirect costs rely
      heavily on changes in work status, total costs are difficult to calculate for
      many women and students as well as elderly and disabled patients. These
      methodologic challenges notwithstanding, the toll of lumbar disc disorders is
      enormous, underscoring the critical importance of identifying strategies to
      prevent these disorders and their consequences.

PMID- 16595439
TI  - Extracellular matrix in disc degeneration.
AB  - The extracellular matrix of the intervertebral disc structures contains many
      molecules also found in cartilage. The extremely polyanionic proteoglycans play a
      central role, particularly in the nucleus, by creating an osmotic environment
      leading to retention of water and ensuing resistance to deformation-important for
      the resilience of the tissue. Another major structural entity particularly
      important in the anulus is the network of collagen fibers; fibril-forming
      collagen 1 is a major constituent. The collagen fibrils in the anulus are largely
      oriented in sheets around the nucleus. A number of molecules present in the
      matrix regulate and direct the collagen fibril assembly by interacting with the
      collagen molecule and also the formed fibril. Several of these molecules bind by
      one domain to the collagen fiber and present another functional domain to
      interact either with other fibers or with other matrix constituents. In this
      manner the collagen fibers are cross-linked into a network that provides tensile
      strength and distributes load over large parts of the anulus. Diminished function
      in these cross-bridging molecules will lead to loss of mechanical properties of
      the collagen network and result in an impaired ability of the anulus to resist
      forces delivered by compression of the disc and particularly the nucleus. A
      different network abundant in the disc and in other load-bearing tissues is based
      on the beaded filaments of collagen 6. The basic building block is a tetramer of
      two pairs of antiparallel collagen-6 molecules arranged such that two N-terminal
      ends of collagen 6 are exposed at either end of the unit. Further assembly occurs
      both by end-to-end and side-to-side associations. This process is catalyzed by
      both biglycan and decorin, where the combined effect of direct binding of the
      core protein to the collagen-6 N-terminal globular domain and the presence of the
      glycosaminoglycan side chain is essential. These ligands are bound at the same
      site in complexes extracted from the tissue and then also have one bound molecule
      of matrilin-1, 2, or 3, in turn bound to a collagen fiber, a procollagen
      molecule, or an aggrecan. Interactions at the cell surface provide signals to the
      cells with regard to the conditions of the matrix. Such interactions include
      binding by matrix components to various receptors at the cell surface. Remodeling
      of the matrix takes place in response to various factors. An early event in
      disease is degradation of aggrecan by the members of the ADAMTS (a disintegrin
      like and metalloprotease with thrombospondin motifs) family and degradation of
      molecules important in maintaining the collagen network.

PMID- 16595440
TI  - Nutrient supply and intervertebral disc metabolism.
AB  - The metabolic environment of disc cells is governed by the avascular nature of
      the tissue. Because cellular energy metabolism occurs mainly through glycolysis,
      the disc cells require glucose for survival and produce lactic acid at high
      rates. Oxygen is also necessary for cellular activity, although not for survival;
      its pathway of utilization is unclear. Because the tissues are avascular, disc
      cells depend on the blood supply at the margins of the discs for their nutrients.
      The nucleus and inner anulus of the disc are supplied by capillaries that arise
      in the vertebral bodies, penetrate the subchondral bone, and terminate at the
      bone-disc junction. Small molecules such as glucose and oxygen then reach the
      cells by diffusion under gradients established by the balance between the rate of
      transport through the tissue to the cells and the rate of cellular demand.
      Metabolites such as lactic acid are removed by the reverse pathway. The
      concentrations of nutrients farthest from the source of supply can thus be low;
      oxygen concentrations as low as 1% have been measured in the discs of healthy
      animals. Although gradients cannot be measured easily in humans, they can be
      calculated. Measured concentrations in surgical patients are in agreement with
      calculated values.

PMID- 16595441
TI  - Modeling changes in intervertebral disc mechanics with degeneration.
AB  - Mechanical response of the spine to various dynamic loading conditions can be
      analyzed by way of in vitro and in vivo studies. Ethical concerns, interpretation
      of conclusions reached in animal studies, and lack of detailed stress
      distributions in the disc components are the major disadvantages of relying
      solely on in vivo studies. Intraspecimen variability, difficulty in including
      muscle activity, and inability to mimic fluid exchange into the disc during
      unloading are some of the disadvantages of in vitro models. The poroelastic
      finite element models can provide a method of understanding the relationship
      between biomechanical performance of the disc due to cyclic loading and disc
      degeneration. A poroelastic finite element model, including regional variation of
      strain-dependent permeability and osmotic pressure, was used to study the effect
      of disc degeneration on biomechanical properties as well as propagation of
      failure in the disc components when cyclic loading was applied to the lumbar
      disc. The results predicted that healthy discs were much more flexible than
      degenerated discs, and the disc stiffness decreased with increasing the number of
      load cycles independent of degenerative condition. Failure was found to progress
      as the drained elastic properties of the disc components decreased due to the
      presence of failure. Poroelastic finite element modeling, including strain
      dependent permeability and osmotic pressure, is the most advanced analytical tool
      currently available that can be used to understand how cyclic loading affects the
      biomechanical characteristics of a degenerated lumbar disc. However, a complete
      understanding of behavior of the intervertebral disc will ultimately be achieved
      only with use of a combination of computational models together with in vitro and
      in vivo experimental methods. Finite element models of discs with varying degrees
      of disc degeneration will help clinicians understand the initiation and
      progression of disc failure and degeneration and will assist in the development
      of approaches to stimulate the regeneration of disc tissues.

PMID- 16595442
TI  - Effects of mechanical loading on intervertebral disc metabolism in vivo.
AB  - The overall goal of this work is to define more clearly which mechanical loading
      conditions are associated with accelerated disc degeneration. This article
      briefly reviews recent studies describing the effects of mechanical loading on
      the metabolism of intervertebral disc cells and defines hypothetical models that
      provide a framework for quantitative relationships between mechanical loading and
      disc-cell metabolism. Disc cells respond to mechanical loading in a manner that
      depends on loading magnitude, frequency, and duration. On the basis of the
      current data, four models have been proposed to describe the effects of
      continuous loading on cellular metabolism: (1) on/off response, in which
      messenger ribonucleic acid (mRNA) transcription remains altered for the duration
      of loading; (2) maintenance, characterized by an initial change in mRNA levels
      with return to baseline levels; (3) adaptation, in which mRNA transcription is
      altered and remains at a new steady state; and (4) no response. In addition, five
      hypothetical mechanisms that describe the long-term consequences of these
      metabolic changes on disc-remodeling are presented. The transient nature of gene
      expression along with enzyme activation/inhibition is associated with changes at
      the protein level. The hypothetical models presented provide a framework for
      obtaining quantitative relationships between mechanical loading, gene expression,
      and changes at the compositional level; however, additional factors, such as
      regulatory mechanisms, must also be considered when describing disc-remodeling. A
      more quantitative relationship between mechanical loading effects and the
      metabolic response of the disc will contribute to injury prevention, facilitate
      more effective rehabilitation treatments, and help realize the potential of
      biologic and tissue engineering approaches toward disc repair.

PMID- 16595443
TI  - Cell deformation and micromechanical environment in the intervertebral disc.
AB  - The purpose of this research was to explore the in situ anatomic and mechanical
      environment of disc cells. Laser scanning confocal microscopy was used to
      characterize three-dimensional morphology of intervertebral disc cells,
      micromechanical deformation and interaction with extracellular matrix, and
      functional intercellular communication. Bovine coccygeal discs were used for both
      the anatomic and micromechanical investigations. Anulus fibrosus cells had a
      complex morphology with sinuous processes woven into the extracellular matrix,
      particularly in the outer aspect of the anulus where they were also
      interconnected via functional gap junctions. They were also found in an extensive
      pericellular matrix of type-VI collagen, joining as many as ten cells into linear
      cell arrays that could be extracted from the matrix as functional units.
      Mechanically, collagen fibril sliding was demonstrated to govern cell mechanics
      and strain transfer in the anulus fibrosus during loading activities. Lamellar
      cells were largely protected from direct tensile strains in the matrix, with
      minimal intercellular strains. However, intercellular strains between lamellar
      cells in adjacent arrays were large, illustrating shearing between linear cell
      arrays. Appreciable shear was observed across the lamellar cell bodies as well as
      to the cellular processes woven into the matrix. These findings demonstrated the
      morphologic and micromechanical complexity of anulus fibrosus cells. The
      knowledge of the in situ environment of disc cells will provide a base to
      investigate the mechanical implications of disc degeneration on the cellular
      environment and to better understand how mechanical and genetic risk factors can
      impact the cells that are essential to maintaining the intervertebral disc.

PMID- 16595444
TI  - Mechanobiology of the intervertebral disc and relevance to disc degeneration.
AB  - Mechanical loading of the intervertebral disc may contribute to disc degeneration
      by initiating degeneration or by regulating cell-mediated remodeling events that
      occur in response to the mechanical stimuli of daily activity. This article is a
      review of the current knowledge of the role of mechanical stimuli in regulating
      intervertebral disc cellular responses to loading and the cellular changes that
      occur with degeneration. Intervertebral disc cells exhibit diverse biologic
      responses to mechanical stimuli, depending on the loading type, magnitude,
      duration, and anatomic zone of cell origin. The innermost cells respond to low-to
      moderate magnitudes of static compression, osmotic pressure, or hydrostatic
      pressure with increases in anabolic cell responses. Higher magnitudes of loading
      may give rise to catabolic responses marked by elevated protease gene or protein
      expression or activity. The key regulators of these mechanobiologic responses for
      intervertebral disc cells will be the micromechanical stimuli experienced at the
      cellular level, which are predicted to differ from that measured for the
      extracellular matrix. Large hydrostatic pressures, but little volume change, are
      predicted to occur for cells of the nucleus pulposus during compression, while
      the highly oriented cells of the anulus fibrosus may experience deformations in
      tension or compression during matrix deformations. In general, the pattern of
      biologic response to applied loads suggests that the cells of the nucleus
      pulposus and inner portion of the anulus fibrosus experience comparable
      micromechanical stimuli in situ and may respond more similarly than cells of the
      outer portion of the anulus fibrosus. Changes in these features with degeneration
      are critically understudied, particularly degeneration-associated changes in cell
      level mechanical stimuli and the associated mechanobiology. Little is known of
      the mechanisms that regulate cellular responses to intervertebral mechanobiology,
      nor is much known with regard to the precise mechanical stimuli experienced by
      cells during loading. Mechanical factors appear to regulate responses of the
      intervertebral disc cells through mechanisms involving intracellular Ca(2+)
      transients and cytoskeletal remodeling that may regulate downstream effects such
      as gene expression and posttranslational biosynthesis. Future studies should
      address the broader biologic responses to mechanical stimuli in intervertebral
      disc mechanobiology, the involved signaling mechanisms, and the apparently
      important interactions among mechanical factors, genetic factors, cytokines, and
      inflammatory mediators that may be critical in the regulation of intervertebral
      disc degeneration.

PMID- 16595445
TI  - Basic science of pain.
AB  - The origin of the theory that the transmission of pain is through a single
      channel from the skin to the brain can be traced to the philosopher and scientist
      Rene Descartes. This simplified scheme of the reflex was the beginning of the
      development of the modern doctrine of reflexes. Unfortunately, Descartes' reflex
      theory directed both the study and treatment of pain for more than 330 years. It
      is still described in physiology and neuroscience textbooks as fact rather than
      theory. The gate control theory proposed by Melzack and Wall in 1965 rejuvenated
      the field of pain study and led to further investigation into the phenomena of
      spinal sensitization and central nervous system plasticity, which are the
      potential pathophysiologic correlates of chronic pain. The processing of pain
      takes place in an integrated matrix throughout the neuroaxis and occurs on at
      least three levels-at peripheral, spinal, and supraspinal sites. Basic strategies
      of pain control monopolize on this concept of integration by attenuation or
      blockade of pain through intervention at the periphery, by activation of
      inhibitory processes that gate pain at the spinal cord and brain, and by
      interference with the perception of pain. This article discusses each level of
      pain modulation and reviews the mechanisms of action of opioids and potential new
      analgesics. A brief description of animal models frames a discussion about recent
      advances regarding the role of glial cells and central nervous system neuroimmune
      activation and innate immunity in the etiology of chronic pain states. Future
      investigation into the discovery and development of novel, nonopioid drug therapy
      may provide needed options for the millions of patients who suffer from chronic
      pain syndromes, including syndromes in which the pain originates from peripheral
      nerve, nerve root, spinal cord, bone, muscle, and disc.

PMID- 16595446
TI  - Pain generation in lumbar and cervical facet joints.
AB  - Facet joints are implicated as a major source of neck and low-back pain. Both
      cervical and lumbar facet syndromes have been described in the medical
      literature. Biomechanical studies have shown that lumbar and cervical facet-joint
      capsules can undergo high strains during spine-loading. Neuroanatomic studies
      have demonstrated free and encapsulated nerve endings in facet joints as well as
      nerves containing substance P and calcitonin gene-related peptide.
      Neurophysiologic studies have shown that facet-joint capsules contain low
      threshold mechanoreceptors, mechanically sensitive nociceptors, and silent
      nociceptors. Inflammation leads to decreased thresholds of nerve endings in facet
      capsules as well as elevated baseline discharge rates. Recent biomechanical
      studies suggest that rear-end motor-vehicle impacts give rise to excessive
      deformation of the capsules of lower cervical facet joints. Still unresolved is
      whether this stretch is sufficient to activate nociceptors in the joint capsule.
      To answer this question, recent studies indicate that low stretch levels activate
      proprioceptors in the facet-joint capsule. Excessive capsule stretch activates
      nociceptors, leads to prolonged neural afterdischarges, and can cause damage to
      the capsule and to axons in the capsule. In instances in which a whiplash event
      is severe enough to injure the joint capsule, facet capsule overstretch is a
      possible cause of persistent neck pain.

PMID- 16595447
TI  - Pathology and possible mechanisms of nervous system response to disc
      degeneration.
AB  - Degeneration of the intervertebral disc is clinically considered to be an
      important source of pain in patients with low-back pain. Disc deterioration
      and/or degeneration may influence the nervous system by stimulation of
      nociceptors in the anulus fibrosus, causing nociceptive pain that is often
      referred to as discogenic pain. The stimulation of the nociceptors may be of
      mechanical or inflammatory origin. Deterioration of a disc with loss of normal
      structure and weight-bearing properties may lead to abnormal motions that cause
      mechanical stimulation. This theory is supported by the fact that patients
      commonly experience an increase in pain with weight-bearing and certain
      movements. In addition, an ingrowth of vessels and nerve fibers into deeper
      layers of the anulus fibrosus has been observed in degenerated discs. A large
      number of inflammatory and signaling substances, such as tumor necrosis factor
      and interleukins (interleukin-1beta, interleukin-6, and interleukin-8), may also
      play a role in the development of back pain. Independent of stimulus of the
      nociceptors, the pain impulses are conducted through myelinated A delta fibers
      and unmyelinated C fibers to the dorsal root ganglion and continue by way of the
      spinothalamic tract to the thalamus and the somatosensory cortex. In response to
      stimulation of the nociceptors in the disc, the somatosensory system may increase
      its sensitivity, resulting in a nonfunctional response; that is, normally
      innocuous stimuli may generate an amplified response (peripheral sensitization).
      When disc degeneration leads to a disc herniation, the adjacent nervous system
      structures, such as the nerve roots or the dorsal root ganglion, can be affected,
      causing neuropathic pain of mechanical or biochemical origin. Disc deterioration
      also influences other spinal structures, such as facet joints, ligaments, and
      muscles, which can also become pain generators. Thus, disc degeneration may be
      responsible for the development of chronic low-back pain without being the actual
      pain focus. Both nociceptive and neuropathic pain can be modulated at higher
      centers, both at the spinal and the supraspinal levels (central sensitization).
      The altered magnitude of perceived pain is often referred to as neural plasticity
      and is considered to play a critical role in the evolution of chronic pain.
      Together with the complexity of the nervous system and pain modulation
      mechanisms, psychological aspects may also play a role in the response of the
      nervous system in patients with chronic low-back pain caused by disc
      degeneration.

PMID- 16595448
TI  - Biologic markers and disc degeneration.
AB  - Biomarkers of skeletal turnover, such as the synthesis and degradation of
      extracellular matrix molecules in specific tissues, offer the opportunity to gain
      new insights into spinal pathology and treatment. The creation, use, and
      interpretation of these analytical body-fluid measures of process (rather than
      outcome) require a clear understanding of the nature of the molecules and events
      being measured. This review provides examples of how protein and carbohydrate
      assays of biomarkers can be used to measure the contribution from the
      intervertebral discs and vertebrae of the spine. With regard to spinal
      degeneration and ankylosing spondylitis, these investigations are providing
      important new information, in weeks rather than years, on the response of
      patients to treatment.

PMID- 16595449
TI  - Innervation, inflammation, and hypermobility may characterize pathologic disc
      degeneration: review of animal model data.
AB  - Animal models provide important clues to the pathomechanisms of human
      intervertebral disc degeneration. Previous reviews on this topic have highlighted
      the fact that loss of nuclear volume (and, consequently, pressure) is a common
      trigger for tissue-remodeling and anatomic change consistent with degeneration in
      humans. Unfortunately, a large gap still exists in the medical knowledge base
      that serves to distinguish symptomatic from asymptomatic degeneration. Because
      disc degeneration per se is not a basis for clinical intervention, identification
      of specific features underlying discogenic pain is of the utmost importance to
      advance the current level of care and identify novel therapeutic targets. This
      article presents animal-model evidence that pathologic, or painful, degeneration
      is characterized by ineffective injury-healing of peripheral tissue. Because the
      disc is only vascularized at the vertebral end plate and the outer part of the
      anulus, these are the likely sites for focal damage, inflammation,
      neoinnervation, and nociceptor sensitization. Consequently, while nuclear
      insufficiency is likely the root of degenerative change, the end plate and
      peripheral part of the anulus are more likely the source of patient discomfort.

PMID- 16595450
TI  - Biologic modification of animal models of intervertebral disc degeneration.
AB  - Intervertebral disc degeneration is a chronic process that can become manifest in
      clinical disorders such as idiopathic low back pain, sciatica, disc herniation,
      spinal stenosis, and myelopathy. The limited available treatment options
      (including discectomy and spinal fusion) for these and other disabling conditions
      that arise from intervertebral disc degeneration are highly invasive, achieve
      limited success, and only address acute symptoms while doing nothing to halt the
      process of degeneration. Although the precise pathophysiology of intervertebral
      disc degeneration has yet to be clearly delineated, the progressive decline in
      aggrecan, the primary proteoglycan of the nucleus pulposus, appears to be a final
      common pathway. Animal models as well as in vitro studies of the process of disc
      degeneration have yielded many potentially useful targets for the reversal of
      disc degeneration. One current research trend is the use of established animal
      models of disc degeneration to study the role of therapeutic modalities in
      reversing the process of degeneration, often with use of the delivery of genes or
      gene products that influence the anabolic and catabolic pathways of the disc.
      This article reviews the ability of gene-product delivery systems and gene
      therapy to alter biologic processes in animal models of disc degeneration and
      examines future trends in this field.

PMID- 16595451
TI  - Relevance of in vitro and in vivo models for intervertebral disc degeneration.
AB  - Models available for the study of intervertebral disc degeneration are designed
      to answer many important questions. In vitro biologic models employ a variety of
      cell, tissue, or organ culture techniques with culture conditions that partially
      mimic the cellular environment of the degenerated human intervertebral disc. In
      vitro biomechanical models include intervertebral disc or motion-segment loading
      experiments as well as finite element modeling techniques. The literature
      describes numerous in vivo animal models for use in the study of intervertebral
      disc degeneration, each of which has its own advantages and disadvantages. Human
      subject studies have included the use of magnetic resonance imaging and other
      techniques to assess diffusion into the intervertebral disc, to measure
      intradiscal pressure, to conduct kinematic or stiffness studies of lumbar motion
      segments, and to evaluate muscular forces on the spine. Although all of these
      studies are helpful in answering specific questions, their relevance in assessing
      disc degeneration in patients with symptoms of discogenic pain must be carefully
      considered.

PMID- 16595452
TI  - Potential biologic therapies for the intervertebral disc.
AB  - Biology offers several strategies for restoring the degenerating disc, including
      the use of recombinant or natural proteins that increase matrix accumulation and
      assembly, enhance the number of disc cells, or in other ways lead to restoration
      of the native healthy disc. Recombinant bone morphogenetic protein-7 (osteogenic
      protein-1) shows promise in this regard. Other growth factors, as well as
      cytokine antagonists such as the interleukin-1 receptor antagonist, are also good
      candidates. Because disc degeneration is a chronic, progressive disorder
      occurring over many years, it is likely that growth factors and other therapeutic
      proteins will need to be present in the disc for extended periods of time. The
      intradiscal injection of recombinant or natural proteins is unlikely to fulfill
      this requirement. In this scenario, the delivery of genes that encode the protein
      in question may provide a better delivery system. Kang and associates have
      pioneered this strategy, demonstrating the responsiveness of disc cells to in
      situ genetic modification. The success of protein and gene therapy requires the
      presence of an adequate number of responding cells. Disc degeneration is
      accompanied by a decline in cellularity. Restoring cell numbers could be achieved
      by either stimulating the division and inhibiting the death of endogenous cells
      or by introducing new cells into the disc. The latter strategy may be more
      successful, especially if the endogenous cells of a degenerating disc are
      unresponsive or otherwise abnormal. When pursuing this strategy, there are
      several important reasons why it is better to introduce progenitor cells than to
      attempt to harvest and reintroduce mature disc cells. Progenitor cells of the
      mesenchymal lineage, available from bone marrow, fat, and other convenient
      sources, could be useful. However, although the presumption exists that these
      types of cells can differentiate into disc cells, this has never been
      demonstrated. One impediment to confirming differentiation into a disc cell is
      our inability to identify these cells; there are no robust molecular,
      biochemical, or biologic markers. The serious study of disc-cell biology at this
      level would be most rewarding.

PMID- 16595453
TI  - Wear particles.
AB  - Particulate and ionic debris resulting from in vivo degradation of total joint
      replacement components are recognized as major factors limiting the longevity of
      the joint reconstruction and the overall success of the procedure. Particulate
      and ionic wear and corrosion debris have been associated with a locally
      aggressive biologic response that can lead to synovitis, periprosthetic bone
      loss, and aseptic loosening of the implants. Furthermore, concerns exist
      regarding the systemic dissemination of prosthetic debris, including potential
      effects resulting from end-organ retention. The long-term success of total disc
      arthroplasty may well depend, at least in part, on the ability to minimize
      implant debris generation and the subsequent local and systemic response.

PMID- 16595454
TI  - Test protocols for evaluation of spinal implants.
AB  - Prior to implantation, medical devices are subjected to rigorous testing to
      ensure safety and efficacy. A full battery of testing protocols for implantable
      spinal devices may include many steps. Testing for biocompatibility is a
      necessary first step. On selection of the material, evaluation protocols should
      address both the biomechanical and clinical performance of the device. Before and
      during mechanical testing, finite element modeling can be used to optimize the
      design, predict performance, and, to some extent, predict durability and efficacy
      of the device. Following bench-type evaluations, the biomechanical
      characteristics of the device (e.g., motion, load-sharing, and intradiscal
      pressure) can be evaluated with use of fresh human cadaveric spines. The
      information gained from cadaveric testing may be supplemented by the finite
      element model-based analyses. Upon the successful completion of these tests,
      studies that make use of an animal model are performed to assess the structure,
      function, histology, and biomechanics of the device in situ and as a final step
      before clinical investigations are initiated. The protocols that are presently
      being used for the testing of spinal devices reflect the basic and applied
      research experience of the last three decades in the field of orthopaedic
      biomechanics in general and the spine in particular. The innovation within the
      spinal implant industry (e.g., fusion devices in the past versus motion
      preservation devices at present) suggests that test protocols represent a dynamic
      process that must keep pace with changing expectations. Apart from randomized
      clinical trials, no single test can fully evaluate all of the characteristics of
      a device. Due to the inherent limitations of each test, data must be viewed in a
      proper context. Finally, a case is made for the medical community to converge
      toward standardized test protocols that will enable us to compare the vast number
      of currently available devices, whether on the market or still under development,
      in a systematic, laboratory-independent manner.

PMID- 16595455
TI  - Directions for future research.

PMID- 16595456
TI  - Predictors of functional outcome two years following revision hip arthroplasty.
AB  - BACKGROUND: Little is known about factors that might predict functional outcome
      following revision hip arthroplasty. The purpose of this study was to identify
      predictors of pain and physical function at two years following revision total
      hip arthroplasty and to evaluate whether the time that the patient waited for the
      surgery and whether the patient had complications were significant predictors of
      outcome. METHODS: One hundred and twenty-six patients (126 hips) were entered
      prospectively into the study when their name was placed on the waiting list for
      surgery. Baseline measures included demographic factors, comorbidities, and the
      responses to the Short Form-36 (SF-36) and Western Ontario and McMaster
      Universities Osteoarthritis (WOMAC) questionnaires. Follow-up was carried out at
      six-month intervals while the patient was waiting for the surgery; within one
      week prior to the surgery; and at six, twelve, and twenty-four months after the
      surgery. Patient age and gender, the preoperative WOMAC pain and function scores,
      the physical and mental component scores of the SF-36, comorbidities, the number
      of revisions, bilateral joint replacement, and the severity of the revision were
      evaluated as possible predictors of ultimate pain and function as measured with
      the WOMAC instrument. RESULTS: The mean age of the patients was 68.6 years.
      Improvement in WOMAC pain and function scores plateaued at six months. The mean
      pain score (and standard deviation) improved from 9.4 +/- 4.1 points
      preoperatively to 3.9 +/- 3.9 points at six months postoperatively, and the mean
      function score improved from 35.4 +/- 14.1 to 19.1 +/- 13.2 points. Preoperative
      pain (p = 0.002) and comorbidity (p = 0.02) were significant predictors of pain
      at two years. There was a trend toward preoperative function predicting function
      at twenty-four months (p = 0.07). There was no significant deterioration in the
      WOMAC pain or function score while the patients waited for surgery. Twenty-eight
      patients had complications. When the time that the patient waited for the surgery
      and complications were added to the models, only complications were found to be
      predictive of outcome (p = 0.04 for pain and p = 0.05 for function). Four
      patients required repeat revision during the follow-up period. CONCLUSIONS:
      Patients with better preoperative pain scores and fewer comorbidities have better
      outcomes following revision total hip arthroplasty. Although the time that the
      patient waited for the revision was not predictive of the ultimate WOMAC pain and
      function scores, we believe that performing revision arthroplasty before the
      patient has substantial functional compromise potentially improves the outcome.

PMID- 16595457
TI  - The accuracy of computed tomography for the diagnosis of tibial nonunion.
AB  - BACKGROUND: When a patient is seen with a possible tibial nonunion and equivocal
      findings on plain radiographs, the surgeon may choose to obtain a computed
      tomography scan to better delineate the bone anatomy. However, the sensitivity
      and specificity of computed tomography in this setting is not known. We
      investigated the accuracy of computed tomography for detecting nonunion in this
      clinical situation. METHODS: Thirty-five patients with equivocal findings on
      plain radiographs underwent computed tomography scanning. The patients were first
      seen at an average of 9.7 months after the injury and had undergone a mean of 2.6
      prior operations. A so-called gold standard of union or nonunion was determined
      by either surgical findings (for twenty-five patients who were operatively
      treated) or six months of clinical observation (for ten patients who had
      nonoperative treatment). Computed tomography scans were assessed by two
      radiologists and one orthopaedic surgeon who were blinded to the clinical
      outcome. RESULTS: Computed tomography scans displayed very good diagnostic
      accuracy. Intraobserver agreement was high (intraclass correlation coefficient =
      0.89), the sensitivity for detecting nonunion was 100%, and the overall accuracy
      was 89.9%. Computed tomography was limited by a low specificity of 62%, as three
      patients who were diagnosed as having tibial nonunion with computed tomography
      underwent surgery and were found to have a healed fracture. CONCLUSIONS: Computed
      tomography displays very good accuracy in the evaluation of tibial fracture
      healing. However, it is limited by low specificity and may sometimes misrepresent
      a healed fracture as a nonunion. Surgeons must be aware of this pitfall in order
      to accurately determine which patients need surgical intervention.

PMID- 16595458
TI  - Reliability, validity, and responsiveness of the Lysholm knee score and Tegner
      activity scale for patients with meniscal injury of the knee.
AB  - BACKGROUND: A torn meniscus is one of the most common indications for knee
      surgery. The purpose of this study was to determine the psychometric properties
      of the Lysholm knee score and the Tegner activity scale when used for patients
      with a meniscal injury of the knee. METHODS: Test-retest reliability, content
      validity, criterion validity, construct validity, and responsiveness to change
      were determined for the Lysholm score and the Tegner activity scale. Test-retest
      reliability was measured in a group of 122 patients at least two years after they
      had undergone surgery for a meniscal lesion. This group completed a follow-up
      form and then completed it again within four weeks. The other tests were
      performed in a group of 191 patients who had only a meniscal lesion at the time
      of the surgery and a group of 477 patients who had a meniscal lesion and other
      intra-articular lesions. RESULTS: The overall Lysholm score showed acceptable
      test-retest reliability, floor and ceiling effects, criterion validity, construct
      validity, and responsiveness to change. There were unacceptable ceiling effects
      (>30%) for the Lysholm domains of limp, instability, support, and locking. The
      Tegner activity scale showed acceptable test-retest reliability, floor and
      ceiling effects, criterion validity, construct validity, and responsiveness to
      change. CONCLUSIONS: Overall, the Lysholm knee score and the Tegner activity
      scale demonstrated acceptable psychometric performances as outcome measures for
      patients with a meniscal injury of the knee. Some domains of the Lysholm score
      showed suboptimal performance, and the Tegner scale had only a moderate effect
      size. Psychometric testing of other condition-specific knee instruments for
      patients with a meniscal lesion of the knee would be helpful to allow comparison
      of the properties of the various knee instruments.

PMID- 16595459
TI  - Use of cost-effectiveness analysis to evaluate new technologies in orthopaedics.
      The case of alternative bearing surfaces in total hip arthroplasty.
AB  - BACKGROUND: Alternative bearing surfaces offer the potential to reduce wear and
      improve implant longevity following total hip arthroplasty. However, these
      technologies are associated with higher costs, the potential for unintended
      consequences, and uncertain benefits in terms of long-term survival of the
      implants. The purpose of this study was to evaluate the cost-effectiveness of the
      use of alternative bearings in total hip arthroplasty. METHODS: A decision
      analysis model was constructed to estimate the cost-effectiveness of the use of
      alternative bearings for patients undergoing total hip arthroplasty. Model
      inputs, including costs, clinical outcome probabilities, and health utility
      values, were derived from a review of the literature. Sensitivity analyses were
      performed to evaluate the impact of patient age at the time of surgery, implant
      costs, and reductions in revision rates on the cost-effectiveness of alternate
      bearing surfaces. RESULTS: In a population of fifty-year-old patients, use of an
      alternative bearing with an incremental cost of 2000 dollars would be cost-saving
      over the individual's lifetime if it were associated with at least a 19%
      reduction in the twenty-year implant failure rate when compared with the failure
      rate for a conventional bearing. In a population of patients over the age of
      sixty-three years, the same implant would be associated with higher lifetime
      costs than would a conventional bearing, regardless of the presumed reduction in
      the revision rate. Conversely, an alternative bearing that adds only 500 dollars
      to the cost of a conventional total hip arthroplasty could be cost-saving in a
      population of patients over the age of sixty-five years, even if it were
      associated with only a modest reduction in the revision rate. In a population of
      patients over the age of seventy-five years, no alternative bearing would be
      associated with lifetime cost-savings, regardless of the cost or the presumed
      reduction in the revision rate. CONCLUSIONS: The cost-effectiveness of
      alternative bearings is highly dependent on the age of the patient at the time of
      surgery, the cost of the implant, and the associated reduction in the probability
      of revision relative to that associated with conventional bearings. Our findings
      provide a quantitative rationale for requiring greater evidence of effectiveness
      in reducing the probability of implant failure when more costly alternative
      bearings are being considered, particularly for older patients.

PMID- 16595460
TI  - Comparison of the vastus-splitting and median parapatellar approaches for primary
      total knee arthroplasty: a prospective, randomized study.
AB  - BACKGROUND: A vastus-splitting approach for total knee arthroplasty has been
      advocated to preserve function of the extensor mechanism and to decrease the
      prevalence of lateral release. Critics have claimed that there is greater blood
      loss and compromised exposure in large patients who are managed with this
      approach. The purpose of the present study was to compare vastus-splitting and
      median parapatellar approaches for primary total knee arthroplasty. METHODS:
      Forty-two consecutive patients (fifty-one knees) undergoing primary total knee
      arthroplasty were randomized to treatment with a median parapatellar or vastus
      splitting approach. The interval of the vastus muscle split was marked with
      radiopaque vascular clips. Surgical data, functional parameters, and preoperative
      and postoperative electromyograms were assessed. RESULTS: Early (six-month) and
      intermediate-term (five-year) follow-up showed no differences in functional
      parameters, tourniquet time, or the frequency of patellar resurfacing.
      Significantly more lateral releases (p < 0.01) and greater blood loss (p = 0.03)
      occurred in the median parapatellar group. Nine (43%) of twenty-one knees in the
      vastus-splitting group had abnormal electromyographic findings at six months
      postoperatively, whereas all patients in the median parapatellar group had normal
      findings. Seven knees with abnormal electromyographic findings at six months had
      normal findings when restudied at five years; in each of these knees, the vastus
      split had been developed bluntly. The other two knees with abnormal findings at
      six months had had sharp dissection for the muscle split. Both of these knees had
      chronic changes, one with changes indicative of reinnervation and the other with
      ongoing denervation, but neither demonstrated functional compromise. CONCLUSIONS:
      The vastus-splitting approach offers a viable alternative to the median
      parapatellar approach for primary total knee arthroplasty that reduces the need
      for lateral retinacular release without impairment of quadriceps function.
      Electromyographic abnormalities in the quadriceps muscle have no functional
      consequence and most likely represent reversible neurapraxic injury that may be
      avoided by blunt dissection in the vastus medialis muscle.

PMID- 16595461
TI  - Pseudarthrosis in adult spinal deformity following multisegmental instrumentation
      and arthrodesis.
AB  - BACKGROUND: There have been few detailed reports concerning pseudarthrosis
      following spinal instrumentation and arthrodesis in adults with spinal deformity
      since the introduction of modern segmental fixation techniques. The purposes of
      this study were to analyze the prevalence, risk factors, and outcome scores on
      the Scoliosis Research Society Instrument-24 associated with pseudarthrosis
      following instrumentation and arthrodesis for the treatment of spinal deformity
      in adults. METHODS: A clinical and radiographic assessment of 232 adults with
      spinal deformity who were treated surgically at a single institution was
      conducted. The average age of the patients was 40.8 years, and the operation was
      a primary procedure in 150 patients and a revision procedure in eighty-two
      patients. All patients who underwent a long (four vertebrae or more) spinal
      instrumentation and arthrodesis with a minimum follow-up of two years were
      included in the analysis. Clinical outcomes were assessed with the Scoliosis
      Research Society questionnaire. RESULTS: Forty patients had a pseudarthrosis.
      Factors that were found to be significantly associated with pseudarthrosis were
      preoperative thoracolumbar kyphosis of >20 degrees (p < 0.0001), an age of more
      than fifty-five years (p = 0.001), arthrodesis to S1 compared with arthrodesis to
      L5 or a cephalad level (p = 0.002), and arthrodesis of more than twelve vertebrae
      (p = 0.037). Patients with a pseudarthrosis had lower total outcome scores on the
      Scoliosis Research Society questionnaire, on the average, than those without a
      pseudarthrosis (p = 0.001). CONCLUSIONS: The prevalence of pseudarthrosis
      following long arthrodesis with use of modern segmental spinal instrumentation
      for the treatment of spinal deformity in adults was 17%, and the clinical outcome
      in these patients can be negatively affected by the pseudarthrosis.

PMID- 16595462
TI  - Functional outcome after acute compartment syndrome of the thigh.
AB  - BACKGROUND: Acute compartment syndrome of the thigh is an uncommon condition that
      is associated with a high rate of morbidity. Because of its rarity, limited
      information is available on the long-term functional outcome for patients with
      this condition and the factors that affect the clinical result. METHODS: Eighteen
      patients with acute compartment syndrome of the thigh were evaluated at an
      average of sixty-two months after treatment. Functional outcome was evaluated by
      means of physical examination, isokinetic thigh-muscle testing, and validated
      functional outcome scores. RESULTS: Long-term functional deficits were present in
      eight patients, and only five patients had full recovery of thigh-muscle
      strength. The persistent dysfunction was reflected in worse overall functional
      outcome scores. High injury severity scores, ipsilateral femoral fracture,
      prolonged intervals to decompression, the presence of myonecrosis at the time of
      fasciotomy, and an age of more than thirty years were associated with increased
      long-term functional deficits, persistent thigh-muscle weakness, and worse
      functional outcome scores. CONCLUSIONS: Acute compartment syndrome of the thigh
      is often associated with considerable long-term morbidity. Several factors can
      affect the functional outcome, and knowledge of these factors can help in the
      development of a more effective clinical management strategy to reduce long-term
      morbidity.

PMID- 16595463
TI  - Osteogenic effects of traumatic brain injury on experimental fracture-healing.
AB  - BACKGROUND: Heterotopic bone formation has been observed in patients with
      traumatic brain injury; however, an association between such an injury and
      enhanced fracture-healing remains unclear. To test the hypothesis that traumatic
      brain injury causes a systemic response that enhances fracture-healing, we
      established a reproducible model of traumatic brain injury in association with a
      standard closed fracture and measured the osteogenic response with an in vitro
      cell assay and assessed bone-healing with biomechanical testing. METHODS: A
      standard closed femoral fracture was produced in forty-three Sprague-Dawley rats.
      Twenty-three of the rats were subjected to additional closed head trauma that
      produced diffuse axonal injury similar to that observed in patients with a
      traumatic brain injury. Twenty-one days after the procedure, all animals were
      killed and fracture-healing was assessed by measuring callus size and by
      mechanical testing. Sera from the animals were used in subsequent in vitro
      experiments to measure mitogenic effects on established cell lines of committed
      osteoblasts, fibroblasts, and mesenchymal stem cells. RESULTS: Biomechanical
      assessment demonstrated that the brain-injury group had increased stiffness (p =
      0.02) compared with the fracture-only group. There was no significant difference
      in torsional strength between the two groups. Cell culture studies showed a
      significant increase in the proliferative response of mesenchymal stem cells
      after exposure to sera from the brain-injury group compared with the response
      after exposure to sera from the fracture-only group (p = 0.0002). This effect was
      not observed in fibroblasts or committed osteoblasts. CONCLUSIONS: These results
      support data from previous studies that have suggested an increased osteogenic
      potential and an enhancement of fracture-healing secondary to traumatic brain
      injury. Our results further suggest that the mechanism for this enhancement is
      related to the presence of factors in the serum that have a mitogenic effect on
      undifferentiated mesenchymal stem cells.

PMID- 16595464
TI  - Lunate arthroplasty with autologous mesenchymal stem cells in a rabbit model.
AB  - BACKGROUND: There is no ideal treatment for end-stage degenerative wrist
      disorders and subsequent carpal collapse. The purpose of this study was to
      investigate whether autologous cartilage constructs tissue-engineered from bone
      marrow-derived mesenchymal stem cells can be effective for carpal bone
      reconstruction. METHODS: Total lunate excision was performed in twenty-seven
      adult New Zealand White rabbits. Mesenchymal stem cells were isolated from marrow
      and then were culture-expanded. Group-1 rabbits underwent excision only. Group-2
      animals underwent excision followed by implantation of a scaffold consisting of
      gelatin and hyaluronan. Group-3 animals underwent excision followed by
      implantation of a mesenchymal stem cell-seeded scaffold that had been
      preincubated in chondrogenic medium. The group-1 animals were killed at six
      weeks, whereas the group-2 and group-3 animals were killed at six or twelve
      weeks. Tissues were harvested for radiographic and histologic analysis. RESULTS:
      Significant carpal collapse (a 5.4% +/- 2.8% reduction in the carpometacarpal
      index, p < 0.05) was observed in the group-1 animals by six weeks. In contrast,
      the carpal height was maintained in the group-2 and 3 animals. There was no
      radiographic evidence of ossification in the group-1 or 2 animals, whereas there
      was radiographic evidence of ossification in all six group-3 rabbits killed at
      the twelve-week time-point. Histologic sections from the group-3 animals showed
      filling of the lunate space with islands of cartilage with interspersed bone
      ossicles at six weeks. At twelve weeks, there was abundant bone formation as well
      as evidence of neovascularization. Osseous tissue was present in the central
      portions of the constructs while the periphery was lined with cartilage. In
      groups 1 and 2, the lunate space was filled with poorly organized fibrous tissue.
      CONCLUSIONS: Cartilaginous implants preformed from autologous mesenchymal stem
      cells seeded onto biodegradable scaffold can prevent carpal collapse. The newly
      formed osteochondral tissue appears to function as an adequate biologic lunate
      spacer for at least twelve weeks in this animal model.

PMID- 16595466
TI  - Transplantation of osteochondral allografts after cold storage.
AB  - BACKGROUND: Transplantation of fresh osteochondral allografts stored at
      hypothermia into knee cartilage defects is a common procedure; however, the
      length of time that allografts can be stored prior to transplantation is
      controversial and has been determined, in part, by the results of vital stain
      uptake by chondrocytes. This study was performed to further define the limits of
      allograft storage. METHODS: Articular cartilage from six cadavers was stored for
      up to fifty-one days in tissue-culture media, and histologic sections were
      evaluated histomorphometrically to quantify the loss of chondrocytes. Samples of
      the cartilage were also placed into tissue culture to assess cell growth. Animal
      studies were performed in parallel on sixteen adult baboons with osteochondral
      allografts transplanted into the medial femoral condyle. Prior to
      transplantation, all allografts were stored in RPMI-1640 with 10% fetal calf
      serum at 4 degrees to 6 degrees C for up to eighty-five days. The transplants
      were graded on their gross and histological appearance, as well as their
      histochemical properties. RESULTS: Many of the human samples stored at
      hypothermia in culture media for up to forty days retained some recognizable
      chondrocytes, but morphometry showed a gradual, significant decrease in the
      number of chondrocytes after nine days (p = 0.001). In addition, the cell
      outgrowth occurred from all specimens stored for up to fifteen days but not in
      samples stored for longer than thirty-four days. In animal studies, transplanted
      allograft cartilage that had been stored for less than eighteen days looked
      smooth and glistening, but grafts stored for over twenty-one days were pale,
      pitted, fragmented, or yellow, and chondrocytes were absent. CONCLUSIONS: Time
      dependent loss of chondrocytes in articular cartilage stored at hypothermia,
      especially in specimens stored for longer than fifteen to twenty days, was
      observed in this study. Cartilage allografts transplanted into nonhuman primates
      after twenty-one days of storage underwent more severe degenerative changes than
      allografts that had been stored for less than twenty-one days. These findings
      suggest caution when transplanting cartilage stored at hypothermia for over
      twenty days.

PMID- 16595465
TI  - Safety and efficacy of ultraviolet-a light-activated gene transduction for gene
      therapy of articular cartilage defects.
AB  - BACKGROUND: Gene therapies for articular cartilage defects are limited by the
      absence of an in vivo delivery system that can mediate site-specific transduction
      restricted to within the margins of the defect during routine arthroscopy. We
      have proposed the use of ultraviolet light to stimulate gene expression following
      infection by recombinant adeno-associated virus (rAAV). However, research has
      demonstrated that short-wavelength ultraviolet light (ultraviolet C), while
      effective, is neither safe nor practical for this purpose. We evaluated the
      safety and efficacy of long-wavelength ultraviolet light (ultraviolet A) from a
      laser to induce light-activated gene transduction in articular chondrocytes in
      vitro and in vivo. METHODS: The effects of ultraviolet A from a 325-nm helium
      cadmium laser, delivered through a fiberoptic cable, on cytotoxicity,
      mutagenesis, intracellular reactive oxygen species, and light-activated gene
      transduction of human articular chondrocytes were evaluated in dose-response
      experiments of primary cultures. Cytotoxicity was determined by trypan blue
      exclusion. The presence of pyrimidine dimers in purified genomic DNA was
      determined by enzyme-linked immunosorbent assays. Intracellular reactive oxygen
      species levels were determined by flow cytometry at one hour and twenty-four
      hours. In vitro light-activated gene transduction with rAAV vectors expressing
      the green fluorescent protein (eGFP) or beta-galactosidase (LacZ) was determined
      by fluorescence microscopy and bioluminescence assays, respectively. In vivo
      light-activated gene transduction was quantified by stereotactic
      immunohistochemistry for beta-galactosidase in rabbit articular cartilage defects
      in the patellar groove that had been irradiated with +/-6000 J/m2 of ultraviolet
      A one week after direct injection of 10(7) transducing units of rAAV-eGFP.
      RESULTS: Ultraviolet A failed to induce significant cytotoxicity at all fluencies
      below 6000 J/m2. Dose-dependent cytotoxicity was observed at greater fluencies.
      In contrast to ultraviolet C, which induced significant (p < 0.05) pyrimidine
      dimer formation at all fluencies in a dose-dependent manner, ultraviolet A failed
      to induce DNA modifications. Conversely, ultraviolet C proved to be a poor
      inducer of intracellular reactive oxygen species, while ultraviolet A immediately
      induced high levels of intracellular reactive oxygen species, which were
      completely resolved twenty-four hours later. Ultraviolet A demonstrated
      significant light-activated gene transduction effects in vitro, which were dose
      dependent (p < 0.05). In vivo, ultraviolet A mediated a tenfold increase in
      transduction in which 40.8% of the superficial chondrocytes adjacent to the
      defect stained positive for green fluorescent protein compared with 5.2% in the
      knees treated with no ultraviolet A (p < 0.006). CONCLUSIONS: These results
      provide what we believe is the first formal demonstration of an agent that can
      induce rAAV transduction in the complete absence of cytotoxicity and DNA
      modification. They also suggest that the mechanism by which long-wavelength
      ultraviolet light mediates site-specific gene expression is by means of the
      induction of intracellular reactive oxygen species. Finally, laser-derived
      ultraviolet A can be readily transferred through a fiberoptic cable to mediate
      light-activated gene transduction in vivo.

PMID- 16595467
TI  - Anti-apoptotic effects of caspase inhibitors on rat intervertebral disc cells.
AB  - BACKGROUND: Apoptosis is thought to be a critical component of disc degeneration.
      Two main pathways of Fas-mediated apoptosis have been identified: Type I, which
      is the death-inducing signaling complex pathway, and Type II, which is the
      mitochondrial pathway. The apoptotic pathway for anulus fibrosus cells, which is
      phenotypically different from that of nucleus pulposus cells, has not been
      elucidated to our knowledge. The ultimate initiators or executioners of apoptosis
      are caspases. There are also inhibitors of caspases, which have the potential of
      being used as anti-apoptotic therapeutic agents. We therefore undertook this
      study to determine (1) the apoptotic pathway of anulus fibrosus cells and (2) the
      anti-apoptotic potential of caspase inhibitors. METHODS: Rat anulus fibrosus
      cells were isolated, cultured, and placed in either 0% (apoptosis-promoting
      condition) or 10% (normal control) fetal bovine serum. We identified and
      quantified the presence of apoptotic cell death, caspase activities, and loss of
      mitochondrial membrane potential. In addition, we examined the cells for the
      expression of Fas, procaspases, and cytochrome-c. Finally, we analyzed the degree
      of anti-apoptotic effects of caspase inhibitors on the cells in 1% fetal bovine
      serum. RESULTS: The percentage of apoptosis and Fas expression in the cells
      incubated in 0% fetal bovine serum were increased compared with those in the
      cells incubated in 10% fetal bovine serum (both p < 0.001). Caspase-8, 9, and 3
      activities were increased and expression of procaspases was decreased in the 0%
      fetal bovine serum compared with those in the 10% fetal bovine serum (all p <
      0.001). In contrast, the loss of mitochondrial membrane potential and cytochrome
      c release into the cytosol were unchanged in the 0% fetal bovine serum.
      Pancaspase and caspase-8 inhibitors reduced apoptotic cell death (p < 0.001 and p
      < 0.05, respectively), but caspase-9 inhibitor did not reduce apoptotic cell
      death. CONCLUSIONS: Our results suggest that, unlike nucleus pulposus cells,
      anulus fibrosus cells are Fas Type-I cells, which undergo apoptosis through the
      death-inducing signaling complex. We also found that apoptosis of intervertebral
      disc cells can be attenuated by caspase inhibitors.

PMID- 16595468
TI  - Ceramic failure after total hip arthroplasty with an alumina-on-alumina bearing.
AB  - BACKGROUND: The mechanical properties of alumina ceramic, now in its third
      generation, have been markedly improved through the evolution of design features
      and manufacturing processes and the introduction of proof-testing. Nonetheless,
      because of the lack of ductility of alumina ceramic, there is concern regarding
      the risk of fracture during insertion or in vivo use. The purpose of the present
      study was to present a multicenter review of primary total hip arthroplasties
      performed with use of a polyethylene-ceramic composite liner combined with a
      ceramic femoral head, with particular attention to failure of the ceramic
      bearing. METHODS: We evaluated 357 primary total hip arthroplasties that had been
      performed in 319 patients with use of a contemporary alumina-on-alumina bearing
      design incorporating a polyethylene-ceramic composite liner within a titanium
      alloy shell coupled with a 28-mm-diameter ceramic femoral head. The procedures
      were performed at four participating centers from 1998 to 2001. Ceramic failure
      without trauma occurred in six hips (1.7%). All of these hips were revised, and
      the retrieved alumina implants were examined by means of visual inspection and
      scanning electron microscopy equipped with energy-dispersive x-ray spectrometry.
      RESULTS: Two femoral heads fractured during the first postoperative year, and
      four alumina liners fractured after an average of 36.8 months in vivo. All four
      of the explanted alumina liners revealed evidence of rim contact with the metal
      neck of the femoral component. Composition analysis confirmed that surface-stain
      materials were titanium particles transferred from the femoral component.
      CONCLUSIONS: Despite the theoretical improvement in the fracture toughness of a
      polyethylene-alumina composite liner, a relatively high rate of catastrophic
      ceramic bearing surface failure was still observed at the time of short-term
      follow-up. This finding prompted us to discontinue the use of this type of
      alumina bearing design.

PMID- 16595469
TI  - Wear debris inhibition of anti-osteoclastogenic signaling by interleukin-6 and
      interferon-gamma. Mechanistic insights and implications for periprosthetic
      osteolysis.
AB  - BACKGROUND: Wear debris challenge of macrophages provokes the generation of
      proinflammatory cytokines, which contribute to periprosthetic osteolysis.
      However, it is not known whether this effect is accompanied by reprogramming of
      other cytokines present within the periprosthetic tissue that may be involved in
      anti-osteoclastogenic activities. In the present study, we examined the ability
      of wear debris particles to inhibit the signaling of two such cytokines,
      interleukin-6 and interferon-gamma. METHODS: Human osteoclast precursor cells
      were challenged with particles of titanium or polymethylmethacrylate bone cement
      prior to the addition of the cytokines interleukin-6 or interferon-gamma.
      Interleukin-6 signaling was determined by measuring the activation of STAT3
      signal transduction with use of immunoblotting and electrophoretic mobility shift
      assays. Interferon-gamma signaling was determined by measuring the activation of
      STAT1 with use of immunoblotting and electrophoretic mobility shift assays and by
      measuring the expression of interferon-gamma-inducible genes with use of real
      time reverse transcription-polymerase chain reaction assays. Involvement of
      mitogen-activated protein kinases in cytokine signaling was assessed by including
      mitogen-activated protein kinase inhibitors in these assays and also by means of
      immunoblot assessment of mitogen-activated protein kinase activation by wear
      debris particles. Wear debris modulation of expression of the cytokine
      suppressors SOCS1 and SOCS3 (as well as pro-inflammatory mediators) was assessed
      with use of real-time reverse transcription-polymerase chain reaction assays.
      RESULTS: Both titanium and polymethylmethacrylate particles potently inhibited
      interleukin-6-induced STAT3 activation in human osteoclast precursor cells.
      Inhibition of p38 mitogen-activated protein kinase, which is activated by
      titanium and polymethylmethacrylate, reversed the inhibitory effects of these
      particles on interleukin-6 signaling, whereas inhibition of ERK and JNK mitogen
      activated protein kinases (which are also activated by both types of wear debris)
      had no effect. Titanium and polymethylmethacrylate also both induced expression
      of SOCS3, an inhibitor of interleukin-6 signaling. In addition to its effects on
      interleukin-6 signaling, titanium also profoundly inhibited the interferon-gamma
      induced activation of STAT1 and the expression of interferon-gamma-inducible
      genes, whereas polymethylmethacrylate had no effect on interferon-gamma
      signaling. CONCLUSIONS: Titanium inhibits both interferon-gamma and interleukin-6
      signaling in human osteoclast precursor cells, whereas polymethylmethacrylate
      bone cement inhibits only the latter. Wear particle inhibition of interleukin-6
      specifically involves the activation of p38 mitogen-activated protein kinase and
      is accompanied by substantial induction of SOCS3, an inhibitor of interleukin-6
      signaling. In contrast, titanium inhibition of interferon-gamma signaling is not
      dependent on mitogen-activated protein kinase activation and is accompanied by
      only modest induction of the interferon-gamma inhibitor SOCS1.

PMID- 16595470
TI  - Association of a large lateral extension of the acromion with rotator cuff tears.
AB  - BACKGROUND: Factors predisposing to tearing of the rotator cuff are poorly
      understood. We have observed that the acromion of patients with a rotator cuff
      tear very often appears large on anteroposterior radiographs or during surgery.
      The purpose of this study was to quantify the lateral extension of the acromion
      in patients with a full-thickness rotator cuff tear and in patients with an
      intact rotator cuff. METHODS: The lateral extension of the acromion was assessed
      on true anteroposterior radiographs made with the arm in neutral rotation. The
      distance from the glenoid plane to the lateral border of the acromion was divided
      by the distance from the glenoid plane to the lateral aspect of the humeral head
      to calculate the acromion index. This index was determined in a group of 102
      patients (average age, 65.0 years) with a proven full-thickness rotator cuff
      tear, in an age and gender-matched group of forty-seven patients (average age,
      63.7 years) with osteoarthritis of the shoulder and an intact rotator cuff, and
      in an age and gender-matched control group of seventy volunteers (average age,
      64.4 years) with an intact rotator cuff as demonstrated by ultrasonography.
      RESULTS: The average acromion index (and standard deviation) was 0.73 +/- 0.06 in
      the shoulders with a full-thickness tear, 0.60 +/- 0.08 in those with
      osteoarthritis and an intact rotator cuff, and 0.64 +/- 0.06 in the asymptomatic,
      normal shoulders with an intact rotator cuff. The difference between the index in
      the shoulders with a full-thickness supraspinatus tear and the index in those
      with an intact rotator cuff was highly significant (p < 0.0001). CONCLUSIONS: A
      large lateral extension of the acromion appears to be associated with full
      thickness tearing of the rotator cuff.

PMID- 16595471
TI  - Additive enhancement of implant fixation following combined treatment with rhTGF
      beta2 and rhBMP-2 in a canine model.
AB  - BACKGROUND: Gaps at the interface between implant and bone increase the risk of
      diminished implant fixation and eventual loosening. The purpose of the present
      study was to determine if combined use of recombinant human transforming growth
      factor-beta 2 (rhTGF-beta2) and bone morphogenetic protein 2 (rhBMP-2) led to
      greater implant fixation strength in the presence of interface gaps than the use
      of either growth factor alone. METHODS: Twenty-eight skeletally mature adult male
      dogs received one porous-coated titanium implant in the proximal part of each
      humerus, for a total of fifty-six implantation sites. Spacers were used to
      establish an initial 3-mm gap between the implant and the host bone at all fifty
      six sites. Forty-two implants were coated with hydroxyapatite-tricalcium
      phosphate and were used in three growth-factor-treatment groups in which the
      implants placed in the left humerus were loaded with 12 microg of rhTGF-beta2
      (Group 1, seven animals), 25 microg of rhBMP-2 (Group 2, seven animals), or 12
      microg of rhTGF-beta2 combined with 25 microg of rhBMP-2 (Group 3, seven
      animals). In these animals, the twenty-one implants that were placed in the right
      humerus were loaded with buffer only to serve as contralateral controls. In Group
      4 (seven animals), the implants were not coated with hydroxyapatite-tricalcium
      phosphate, the gap in the left humerus was lightly packed with autogenous bone
      graft, and the gap in the right humerus was left empty to serve as a
      contralateral control. All animals were killed at twenty-eight days. The primary
      end points included three mechanical variables: fixation strength, interface
      stiffness, and energy to failure. Secondary end points included bone ingrowth and
      bone volume and trabecular architecture in the gap and in a region located 2 mm
      medial to the implantation site. RESULTS: The hydroxyapatite-tricalcium phosphate
      coating had no effect on implant fixation, bone ingrowth, or bone formation in
      the 3-mm gap. Individual growth factor treatments led to 2.3 to 3.2-fold
      increases in fixation strength and stiffness as compared with the values for the
      contralateral controls (p < 0.05). The combined growth factor treatment led to
      5.7-fold increases in fixation strength and stiffness compared with the values
      for the contralateral controls (p < 0.01). Autogenous bone graft treatment was
      associated with 4.5 to 6.4-fold increases in implant fixation strength and
      stiffness as compared with the values for the contralateral controls (p < 0.01).
      Compared with the relevant contralateral controls, energy to failure was
      increased 3.5-fold in association with TGF-beta2 alone (p < 0.05), 4.5-fold in
      association with TGF-beta2 combined with BMP-2 (p < 0.01), and 2.5-fold in
      association with autogenous bone-grafting. As much as 63% of the variance in the
      mechanical end points was associated with variance in bone volume and
      architecture in the 3-mm gap and in the region of interest located 2 mm medial to
      the implantation site (p < 0.01). CONCLUSIONS: In this animal model, the combined
      use of TGF-beta2 and BMP-2 led to more secure mechanical fixation of the implant
      than did the use of either growth factor alone and demonstrated results that were
      similar to those associated with the use of autogenous bone graft.

PMID- 16595472
TI  - The correlation of specific orthopaedic features of polyostotic fibrous dysplasia
      with functional outcome scores in children.
AB  - BACKGROUND: Polyostotic fibrous dysplasia has a wide clinical spectrum, with
      substantial variation between patients in terms of orthopaedic manifestations,
      including the number of fractures, the degree of deformity of the limbs, and the
      presence of scoliosis. Data from bone scans, skeletal surveys, and records were
      correlated with the Pediatric Outcomes Data Collection Instrument scales to
      examine whether any specific facet of orthopaedic involvement could be related to
      functional abilities. METHODS: All patients who were sixteen years of age or
      younger and who were part of an ongoing natural history study of polyostotic
      fibrous dysplasia (including McCune-Albright syndrome) were sent an age
      appropriate Pediatric Outcomes Data Collection Instrument outcomes tool. The
      medical records and radiographs of the patients who returned forms were reviewed.
      Radiographic measurements of scoliosis, the femoral neck-shaft angle, and limb
      deformities were then performed. The extent of skeletal involvement with
      polyostotic fibrous dysplasia (disease burden) was assessed on bone scans with
      use of a validated tool. A chart review was performed to determine the fracture
      rate, the use of bisphosphonates, and the endocrine status. These measurements
      were correlated with the Pediatric Outcomes Data Collection Instrument scores.
      RESULTS: The outcomes tool was sent to twenty-seven patients and the completed
      instrument was returned by twenty patients, for a response rate of 74%. The
      parent-child form was filled out for twelve patients and the parent-adolescent
      form was filled out for eight patients. The mean standardized Pediatric Outcomes
      Data Collection Instrument scores for all twenty patients were lowest for sports
      (62; range, 14 to 100) and happiness (72; range, 25 to 100). Adolescents and
      parents disagreed with regard to sports (with adolescent scores being higher than
      parental scores) and pain (with parental scores being higher than adolescent
      scores). However, the overall global scores correlated well between the parents
      and the adolescents (r = 0.78, p = 0.03). The femoral neck-shaft angle correlated
      strongly with the Pediatric Outcomes Data Collection Instrument score for sports
      (r = 0.46, p = 0.03) but not for transfers. The bone scan scores for the lower
      extremity disease burden correlated with both the transfer scale (r = 0.76, p =
      0.03) and the sports scale (r = 0.77, p = 0.02). Deformity of the limbs, the
      presence of scoliosis, the prevalence of endocrine dysfunction, and the number of
      fractures did not correlate with the Pediatric Outcomes Data Collection
      Instrument scores. CONCLUSIONS: In patients with polyostotic fibrous dysplasia,
      the loss of the normal femoral neck-shaft angle and the disease burden in the
      lower extremities appear to have the greatest effect on functional activity as
      measured with the Pediatric Outcomes Data Collection Instrument tool.

PMID- 16595473
TI  - Morphological changes of collagen fibrils in the subsynovial connective tissue in
      carpal tunnel syndrome.
AB  - BACKGROUND: Pathologic changes occur commonly in the subsynovial connective
      tissue in patients with carpal tunnel syndrome. The purposes of this study were
      to investigate the ultrastructural changes of the subsynovial connective tissue
      in these patients and compare them with the findings in cadaver controls.
      METHODS: The diameter and density of collagen fibrils were measured by
      transmission electron microscopy in specimens of subsynovial connective tissue
      from ten patients with idiopathic carpal tunnel syndrome and from ten fresh
      frozen cadavers of individuals without known symptoms of carpal tunnel syndrome.
      RESULTS: We noted deformed collagen fibrils with a spiraled appearance in the
      specimens from the patients. We also observed phagocytosis of elastin fibrils in
      all of those specimens. These changes were noted only rarely in the cadaver
      controls. The mean diameter (and standard deviation) of the collagen fibrils was
      45.5 +/- 8.0 nm in the control group and 54.8 +/- 15.2 nm in the patient group (p
      < 0.05). The mean number of collagen fibrils per 0.04 microm2 (density) was
      201.38 +/- 48.88 in the control group and 157.08 +/- 54.38 in the patient group
      (p < 0.05). CONCLUSIONS: These ultrastructural findings suggest that subsynovial
      collagen in patients with carpal tunnel syndrome is structurally different from
      that in individuals without carpal tunnel syndrome, but the processes resulting
      in that abnormal morphology remain to be elucidated.

PMID- 16595474
TI  - Results of vascularized rib grafts in complex spinal reconstruction.
AB  - BACKGROUND: The application of vascularized rib grafts in spine surgery has been
      limited to the treatment of kyphosis with anterior placement of the rib graft to
      facilitate anterior spine arthrodesis. The outcomes following use of vascularized
      rib grafts in complex spinal reconstruction have not been adequately evaluated.
      The purpose of this study was to determine the results, including the time to
      osseous union and complications, following anterior or posterior placement of
      pedicled vascularized rib grafts for complex spinal reconstruction. METHODS: The
      medical records and images of all patients in whom a vascularized rib graft had
      been used for a multisegmental spine reconstruction at a single institution
      between 1994 and 2004 were retrospectively reviewed. Eighteen patients (mean age,
      45.3 years) who had been followed for an average of 31.8 months were identified.
      Details regarding indications, the levels that were spanned, the graft length,
      the time to union, and complications were evaluated. RESULTS: The preoperative
      diagnoses included metastatic or primary tumor (thirteen patients) and
      progressive kyphosis secondary to chronic osteomyelitis (two), injury (one),
      congenital anomalies (one), or implant failure (one). On the average, 4.4 levels
      were fused and 1.9 vertebral bodies were excised. All eighteen arthrodeses
      included various forms of allograft and/or autograft material, and
      instrumentation was used, in addition to the vascularized rib graft, in twelve
      patients. The mean rib length was 16.1 cm, and a rib between the fifth and
      eleventh ribs, inclusive, was used, depending on the location of the spinal
      reconstruction. The average time to union was 6.8 months, and all rib grafts
      united. There were no complications specific to the rib-harvesting procedure.
      CONCLUSIONS: The use of a vascularized rib graft in complex spinal reconstruction
      adds little time to the overall procedure, is associated with low morbidity, and
      appears to offer substantial benefits to the patient.

PMID- 16595476
TI  - Failure of LCP condylar plate fixation in the distal part of the femur. A report
      of six cases.

PMID- 16595475
TI  - Treatment of knee flexion contracture due to central nervous system disorders in
      adults.
AB  - BACKGROUND: Studies concerning adult patients with spastic flexion contracture of
      the knee are rare. Such patients frequently have cutaneous and vascular
      complications as well as recurrence of the contracture after treatment. We
      present a strategy consisting of simultaneous correction of all deformities of
      both lower limbs, distal hamstring releases, and application of femorotibial
      external fixation when extension of the knee is limited by excessive posterior
      soft-tissue tension. METHODS: A consecutive series of fifty-nine patients (ninety
      seven knees) between the ages of twenty-one and seventy-seven years received
      surgical treatment for a flexion contracture of the knee secondary to
      neurological impairment. The flexion contracture was bilateral in thirty-eight
      patients. Preoperatively, the mean flexion contracture angle was 69 degrees and
      the mean passive range of motion was 61 degrees. The contracture was corrected,
      through medial and lateral approaches, with distal hamstring lengthening. A
      posterior capsulotomy was performed in thirty-five knees. Full extension of
      thirty-four knees was achieved intraoperatively. In seventy-seven knees, partial
      correction was maintained with a unilateral external fixator, and passive and
      active mobilization was performed four times daily after temporary removal of the
      spanning external fixator rod. RESULTS: At the time of final follow-up, ranging
      from one to five years postoperatively, the mean residual flexion contracture was
      6.2 degrees. Forty-five knees had complete extension, and thirty-nine knees had a
      residual flexion contracture of <10 degrees. No recurrence of the flexion
      contracture or instability was noted in any knee at the time of follow-up. There
      were four cutaneous complications but no vascular or neurological complications.
      CONCLUSIONS: We believe that our surgical strategy for correction of fixed knee
      flexion contracture in adult patients is safe and effective. The correction
      improves nursing care and sitting posture, facilitating the upright position of
      patients who are unable to walk, and improves walking ability for patients who
      are able to walk.

PMID- 16595477
TI  - Nonoperative treatment of vertebral blastomycosis osteomyelitis associated with
      paraspinal abscess and cord compression. A case report.

PMID- 16595478
TI  - Concurrent bilateral femoral neck stress fractures and osteonecrosis of the hip.
      A case report.

PMID- 16595479
TI  - Midfoot coccidioidal osteomyelitis. A case report and review of the literature.

PMID- 16595480
TI  - Retrieval of a trial femoral head that displaces into the periacetabular soft
      tissue during mini-incision total hip arthroplasty. A case report.

PMID- 16595481
TI  - Diagnosis of periprosthetic infection.
AB  - Periprosthetic infections are rare, but there is evidence to suggest that their
      frequency may be underestimated. No single laboratory test has perfect
      sensitivity and specificity for diagnosing infection. Most tests have better
      specificity when they are performed for patients in whom infection is suspected
      clinically rather than when they are used as screening tests. Screening test
      results that may suggest the possibility of infection include elevation of the
      erythrocyte sedimentation rate and/or serum C-reactive protein level more than
      three months after an arthroplasty. Most serologic tests are difficult to
      interpret when the patient has an underlying inflammatory arthropathy. Cultures
      of aspirated joint fluid can be especially helpful for patients who have symptoms
      suggestive of infection, but their results are best interpreted two weeks after
      administration of antibiotics has been discontinued. Joint fluid cell counts may
      also be helpful, but Gram stains of joint fluid have poor sensitivity and
      specificity. Criteria for diagnosing infection on the basis of frozen sections of
      implant membranes have not yet been standardized, but in many laboratories more
      than five neutrophils per high-power field in five or more fields (excluding
      surface fibrin) has been found to be suggestive of infection. Most polymerase
      chain reactions that detect the universal 16S rRNA bacterial gene have problems
      with false-positive results, but combining a universal polymerase chain reaction
      with subsequent bacterial sequencing can help improve specificity. Polymerase
      chain reactions can detect necrotic bacteria, so the clinical importance of
      positive results of this analysis in the absence of other features of infection
      remains to be determined.

PMID- 16595482
TI  - Intervertebral disc degeneration. Summary of an AAOS/NIH/ORS workshop, September
      2005.

PMID- 16595483
TI  - The continuing development of shoulder replacement: "reaching the surface".

PMID- 16595484
TI  - A family's request for deception.

PMID- 16595485
TI  - What's new in foot and ankle surgery.

PMID- 16595486
TI  - Using radiolabeled DNA as an imaging agent to recognize protein targets.

PMID- 16595487
TI  - Bone marrow hypermetabolism on 18F-FDG PET as a survival prognostic factor in non
      small cell lung cancer.
AB  - PET is now widely used in the diagnosis and staging of lung cancer with (18)F
      FDG. The purpose of the study was to evaluate the prognostic value of diffuse
      bone marrow hypermetabolism along with other PET prognostic factors with respect
      to survival and compare them with other established prognostic factors in a large
      cohort of patients. METHODS: Of 255 patients referred for evaluation of a
      suspicious lung lesion by PET over an 8-mo period (May 1999 to January 2000), the
      outcome of 120 patients with a final diagnosis of primary non-small cell lung
      cancer was analyzed retrospectively after excluding subjects with benign,
      metastatic, or recurrent lesions, using the available follow-up information and a
      provincial mortality database. Kaplan-Meier survival curves were compared using
      the mean and the maximal tumor standardized uptake value (SUV), bone marrow SUV,
      PET stage, various laboratory parameters, sex, age, conventional imaging stage,
      and pathologic stage. A stepwise Cox proportional hazard model was built using
      the significant variables on univariate analysis. RESULTS: The primary tumor SUV
      (>10), bone marrow uptake of (18)F-FDG, (18)F-FDG PET stage, pathologic stage,
      hypercalcemia, lactate dehydrogenase, hemoglobin, albumin, thrombocytopenia,
      thrombocytosis, and leukocytosis were predictors of mortality on univariate
      analysis. On multivariate analysis, bone marrow hypermetabolism, (18)F-FDG PET
      nodal stage, and some hematologic parameters (hemoglobin, platelets, white blood
      cell counts) remained significant independent predictors of mortality.
      CONCLUSION: Bone marrow hypermetabolism and the PET nodal stage were strong
      independent predictors of mortality in patients with lung cancer. The primary
      tumor SUV, though predictive on univariate analysis, was not an independent
      predictor of mortality in our model.

PMID- 16595488
TI  - Gluc-Lys([18F]FP)-TOCA PET in patients with SSTR-positive tumors: biodistribution
      and diagnostic evaluation compared with [111In]DTPA-octreotide.
AB  - A recently developed (18)F-labeled PET tracer for somatostatin receptor (sstr)
      imaging, N(alpha)-(1-deoxy-D-fructosyl)-N(epsilon)-(2-[(18)F]fluoropropionyl)
      Lys(0)-Tyr(3)-octreotate (Gluc-Lys([(18)F]FP)-TOCA), was evaluated in patients
      with sstr-positive tumors by assessing the pharmacokinetics, biodistribution, and
      diagnostic performance in comparison with [(111)In]DTPA-octreotide. METHODS:
      Twenty-five patients with different sstr-positive tumors were included in the
      study and were injected with 105 +/- 50 MBq Gluc-Lys([(18)F]FP)-TOCA. PET was
      performed up to 120 min with 2 different dynamic imaging protocols. Tracer
      kinetics in tumors and nontumor tissues and tumor-to-background ratios were
      described by region-of-interest analysis and standardized uptake values (SUVs).
      In 16 patients, sstr scintigraphy with [(111)In]DTPA-octreotide was performed
      (whole-body scans and SPECT). Two independent experts on PET and gamma- camera
      scans performed lesion counts. RESULTS: Gluc-Lys([(18)F]FP)-TOCA showed a fast
      and intense tumor accumulation as well as a rapid clearance from blood serum
      (biexponential elimination, with the half-lives of the initial and the terminal
      elimination phase calculated as t(1/2)(1) = 2.3 +/- 1.3 min and t(1/2)(2) = 26.4
      +/- 14.6 min, respectively). Tumor-to-background ratios at 16 +/- 9 min and 34 +/
      12 min were as high as 80% and 90% (% of maximum ratios), respectively. Tumors
      showed high SUVs ranging from 13.7 +/- 2.3 (tumors in lung) up to 26.9 +/- 15.4
      (abdominal tumors). Tracer distribution within tumor and nontumor tissues was
      stable up to 120 min (except spleen). No significant bowel activity was observed.
      Comparison of 29 tumors located in the liver showed a mean tumor-to-background
      ratio of 5.3 +/- 2.6 for Gluc-Lys([(18)F]FP)-TOCA vs. 4.6 +/- 3.3 for
      [(111)In]DTPA-octreotide (P = 0.24). Visual image analysis revealed a
      significantly higher number of lesions (factor of 2.4) and improved interobserver
      correlation (r = 0.99 vs. 0.86) for PET. CONCLUSION: Gluc-Lys([(18)F]FP)-TOCA PET
      allows a fast, high- contrast imaging of sstr-positive tumors. The biokinetics
      and diagnostic performance of Gluc-Lys([(18)F]FP)-TOCA are superior to
      [(111)In]DTPA-octreotide and-as far as can be derived from the literature
      comparable with [(68)Ga]-DOTA-d Phe(1)-Tyr(3)-octreotide ([(68)Ga]DOTATOC).

PMID- 16595489
TI  - Effect of intramyocardial injection of autologous bone marrow-derived mononuclear
      cells on perfusion, function, and viability in patients with drug-refractory
      chronic ischemia.
AB  - Intramyocardial injection of bone marrow cells has been proposed as a new
      therapeutic option for patients with chronic ischemic heart disease. We
      investigated whether autologous bone marrow-derived mononuclear cell injection
      into the myocardium of patients with drug-refractory ischemia reduces anginal
      symptoms, improves left ventricular (LV) function, increases myocardial
      perfusion, and alters the extent of scar tissue. METHODS: In 25 patients (mean
      age +/- SD, 64 +/- 10 y; 21 male) with drug-refractory angina pectoris (Canadian
      Cardiovascular Society [CCS] class III-IV), despite optimized medical therapy and
      without options for conventional revascularization, bone marrow was aspirated
      from the iliac crest. Mononuclear cell injections were targeted at myocardial
      regions with stress-induced ischemia on gated (99m)Tc-tetrofosmin SPECT. Anginal
      symptoms were reassessed at 3- and 6-mo follow-up. At baseline and 3-mo follow
      up, gated (99m)Tc-tetrofosmin SPECT and (18)F-FDG SPECT were performed to assess
      LV function, LV volumes, myocardial perfusion (stress and rest, 17-segment
      model), and extent of scar tissue. RESULTS: Mean CCS score improved from 3.4 +/-
      0.6 at baseline to 2.3 +/- 0.6 at 3 mo (P < 0.01) and remained unchanged at 6 mo
      (2.3 +/- 0.6; P < 0.01 vs. baseline and P = not significant [NS] vs. 3 mo). Gated
      (99m)Tc-tetrofosmin SPECT demonstrated an increased LV ejection fraction (from
      47.6% +/- 13.5% to 54.1% +/- 16.9%; P < 0.01) and a reduced LV end-systolic
      volume (from 81 +/- 68 mL to 75 +/- 70 mL; P < 0.01). Segmental regional wall
      thickening increased from 34% +/- 12% at baseline to 39% +/- 17% at 3-mo follow
      up (P = 0.01). The number of segments with stress-inducible ischemia per patient
      decreased from 4.6 +/- 3.2 to 2.0 +/- 2.6 (P < 0.01). Both segmental stress and
      segmental rest score improved, although the improvement in stress score was more
      pronounced (decrease in segmental stress score 0.22 +/- 0.20 vs. decrease in
      segmental rest score 0.04 +/- 0.06; P < 0.01). Myocardial perfusion improved in
      53% of the injected segments and in 13% of the noninjected segments (P < 0.01).
      The percentage of myocardial segments with some extent of scar remained unchanged
      at 3-mo follow-up (13% vs. 12%; P = NS). CONCLUSION: Autologous bone marrow
      derived mononuclear cell injection in patients with drug-refractory angina and
      chronic ischemia improves anginal symptoms, increases LV function, and
      predominantly enhances myocardial stress perfusion in injected segments, whereas
      the extent of myocardial scar tissue remains unchanged.

PMID- 16595490
TI  - Validation of a blood-sampling method for the measurement of 99mTc-methylene
      diphosphonate skeletal plasma clearance.
AB  - Quantitative studies of bone using (99m)Tc-methylene diphosphonate (MDP) reflect
      bone remodeling. The simplest method of evaluating (99m)Tc-MDP kinetics involves
      taking multiple blood samples and measuring total clearance (K(total)) from the
      area under the plasma curve (AUC) and deriving bone clearance (K(bone)) by
      subtracting glomerular filtration rate (GFR) from K(total). However, the accuracy
      of the AUC method is uncertain because of assumptions that the terminal
      exponential is reached by 2 h and that the rate constant k(4), representing the
      backflow of tracer from bone to plasma, is negligibly small. The aim of this
      study was to validate the accuracy of the AUC method by comparing K(bone) values
      obtained by that method with those obtained by gamma-camera imaging. METHODS:
      Seventy-one patients were injected with 600 MBq of (99m)Tc-MDP. For the first 22
      patients, whole-body images were acquired at 15 min and at 1, 2, 3, and 4 h after
      injection, whereas the remaining 49 were imaged at 15 min and at 1 and 3 h. Two
      minute static images of the thighs were acquired immediately before each whole
      body scan. Multiple blood samples were taken between 5 min and 4 h, and free
      (99m)Tc-MDP was measured using ultrafiltration. Two gamma-camera methods were
      used to evaluate K(bone): the Patlak plot method and the Brenner method, which is
      based on measuring soft-tissue uptake in the thighs. The soft-tissue data were
      also used to measure k(4). RESULTS: The soft-tissue data gave a k(4) value of
      0.0003 min(-1) (95% confidence interval, 0-0.0008 min(-1)). The mean (+/-SD)
      (99m)Tc-MDP K(bone) was 56.0 +/- 32.4 mL x min(-1) with the AUC method, 49.5 +/-
      32.1 mL x min(-1) with the Patlak method, and 42.8 +/- 32.0 mL x min(-1) with the
      Brenner method. Correcting the AUC values of K(total) by factors of 0.95 and 0.90
      gave K(bone) values in agreement with the Patlak and Brenner methods,
      respectively. CONCLUSION: Values of k(4) are too small to affect values of
      K(bone) measured using the AUC method. Correcting K(total) by factors in the
      range of 0.90-0.95 corrects for the error in the terminal exponential and brings
      K(bone) values measured using the AUC method into agreement with the gamma-camera
      results.

PMID- 16595492
TI  - A novel approach to multipinhole SPECT for myocardial perfusion imaging.
AB  - Myocardial perfusion imaging with SPECT remains critically important for
      diagnosing, assessing, and evaluating treatment of coronary artery disease.
      However, conventional rotational SPECT suffers from prolonged study times because
      of relatively low detection efficiency. We therefore have investigated a
      multipinhole collimator that could improve the detection efficiency in cardiac
      SPECT by a factor 5, while providing image quality comparable to standard
      rotational SPECT techniques using parallel-hole collimation. METHODS: We have
      measured the spatial resolution and efficiency of a 9-pinhole and a parallel-hole
      collimator mounted to a standard nuclear medicine gamma-camera as a function of
      distance from the collimator with a point source array. The efficiency was
      derived by integrating the detected counts, and the spatial resolution was
      determined from the full width at half maximum of the detected point spread
      function. In addition, we generated and reconstructed projection data of a 9
      pinhole collimator from a digital heart phantom with a basal lesion. We simulated
      3 scenarios: single view from left anterior, 2 views from left anterior and left
      lateral; and 4 views that include the 2 previous views and left lateral and
      anterior views. RESULTS: We found that the spatial resolution of the 9-pinhole
      collimator with 8-mm diameter pinholes was 30% poorer than that for the parallel
      hole collimator, whereas the detection efficiency was increased by >10-fold. This
      predicts that a 9-pinhole collimator having the same spatial resolution as a
      parallel-hole collimator will have 5 times greater efficiency. Reconstructed data
      from 1 angular view of the 9-pinhole collimator showed the expected loss of
      spatial resolution in the longitudinal direction with reduced resolution of the
      basal lesion. In addition, the tomograms showed distortions in the apical region.
      In contrast, the reconstructed data from 2 and 4 views of the 9-pinhole
      collimator demonstrated good lesion definition and also produced images
      describing the shape and size of the heart more accurately. CONCLUSION: Our
      results indicate that myocardial multipinhole tomography with 2 or more views
      offers an image quality and spatial resolution comparable with current rotational
      SPECT techniques, but with the advantage of a 5-fold increase in efficiency.

PMID- 16595491
TI  - SPECT/CT using 67Ga and 111In-labeled leukocyte scintigraphy for diagnosis of
      infection.
AB  - The present study evaluated the role of SPECT/CT as an adjunct to (67)Ga (GS) or
      (111)In-labeled white blood cell (WBC) scintigraphy for diagnosis or localization
      of infection. METHODS: Eighty-two patients (56 male and 26 female; mean age, 62
      y) assessed for known or suspected infectious processes underwent 88 SPECT/CT
      studies. Forty-seven patients underwent GS SPECT/CT (13 with fever of unknown
      origin, 21 with suspected osteomyelitis, and 13 with suspected soft-tissue
      infection), and 35 patients underwent WBC SPECT/CT (24 with suspected vascular
      graft infection, and 11 with suspected osteomyelitis). Ninety-eight suggestive
      sites were identified (52 on GS and 46 on WBC). Additional information provided
      by SPECT/CT for diagnosis or localization of infection, as compared with planar
      and SPECT scintigraphy, was recorded. The SPECT/CT contribution was analyzed on a
      patient and site basis and was compared for the 2 tracers and clinical
      indications. RESULTS: SPECT/CT provided additional information for infection
      diagnosis and localization in 39 (48%) of 82 patients and in 47 (48%) of 98
      sites. SPECT/CT defined the extent of infection in 35 patients (43%) in 43 sites
      (44%) and excluded infection in 4 suggestive sites defined as physiologic bowel
      uptake on GS. SPECT/CT was incorrect in 2 suggestive sites (1 GS and 1 WBC). The
      contribution of SPECT/CT was significantly higher for WBC than for GS (P < 0.05)-
      in 63% versus 36% of patients, respectively, and in 61% versus 36% of sites,
      respectively. CONCLUSION: SPECT/CT made an incremental contribution to GS and WBC
      in 48% of patients with suspected infections, by improving diagnosis,
      localization, and definition of extent of disease. SPECT/CT has an important role
      mainly with highly specific, low-background infection-seeking tracers such as
      WBC.

PMID- 16595493
TI  - Stunning and its effect on 3H-FDG uptake and key gene expression in breast cancer
      cells undergoing chemotherapy.
AB  - Shortly after chemotherapy, relatively little is known about the expression of
      key genes and proteins involved in glycolysis. Doxorubicin (DOX) and 5
      fluorouracil (5FU) are two commonly used chemotherapy agents that work through
      differing pathways. Glucose transporter-1 (Glut-1) and hexokinase II (HKII)
      proteins are highly expressed in many breast carcinomas, but their status while
      undergoing DOX or 5FU chemotherapy has not been systematically evaluated.
      METHODS: We evaluated, in vitro, the messenger RNA (mRNA) and protein levels of
      Glut-1 and HKII in MCF-7, a breast adenocarcinoma cell line, and (3)H-FDG uptake,
      both in untreated conditions and during treatment with either DOX or 5FU for 24
      h. Six time points were evaluated: untreated at time 0; treated for 1 h; treated
      for 24 h; and 1, 2, and 3 d after chemotherapy. We analyzed tumor cell Glut-1 and
      HKII mRNA expression with real-time polymerase chain reaction and Western
      blotting, (3)H-FDG uptake per cell, and cell viability with a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. RESULTS: DOX was more
      effective than 5FU in killing the cancer cells under our study conditions. In
      untreated MCF-7 cells, the mRNA levels of HKII were typically higher than those
      of Glut-1, and (3)H-FDG uptake was strongly related to Glut-1 mRNA expression
      (R(2) = 0.85). Once treated with either drug, (3)H-FDG uptake declined initially,
      the mRNA ratio was reversed, and Glut-1 mRNA levels were higher than HKII levels.
      This was verified in the protein assay. With DOX treatment, the cells showed
      increased Glut-1 mRNA and decreased HKII mRNA for the duration of active
      treatment; these levels returned to those seen in the untreated cells once the
      treatment was stopped for 24 h. However, HKII protein levels remained somewhat
      low. No correlation was seen between (3)H-FDG uptake and HKII mRNA in DOX- and
      5FU-treated cells (R(2) = 0.14 and 0.0038, respectively). CONCLUSION: After DOX
      or 5FU therapy, the relationship between (3)H-FDG uptake and viable cell number
      can become disjointed, with transient declines in (3)H-FDG uptake in excess of
      the decline in cell number despite increased Glut-1 mRNA levels. This transient
      "stunning" has potential implications for (3)H-FDG PET, especially soon after
      treatment is initiated. However, (3)H-FDG remains a generally valid marker of
      viable cell number after cancer chemotherapy.

PMID- 16595494
TI  - Focal thyroid lesions incidentally identified by integrated 18F-FDG PET/CT:
      clinical significance and improved characterization.
AB  - In this retrospective study, we investigated whether the (18)F-FDG uptake pattern
      and CT findings improved the accuracy over the standardized uptake value (SUV)
      for differentiating benign from malignant focal thyroid lesions incidentally
      found on (18)F-FDG PET/CT. We also defined the prevalence of these lesions and
      their risk for cancer. METHODS: (18)F-FDG PET/CT was performed on 1,763 subjects
      without a previous history of thyroid cancer from May 2003 to June 2004. Two
      nuclear medicine physicians and 1 radiologist interpreted PET/CT images,
      concentrating on the presence of focal thyroid lesions, the maximum SUV of the
      thyroid lesion, the pattern of background thyroid (18)F-FDG uptake, and the CT
      attenuation pattern of the thyroid lesion. RESULTS: The prevalence of focal
      thyroid lesions on PET/CT was 4.0% (70/1,763). Diagnostic confirmation was done
      on 44 subjects by ultrasonography (US)-guided fine-needle aspiration (n = 29) or
      US with clinical follow-up (n = 15). Among 49 focal thyroid lesions in these 44
      subjects, 18 focal thyroid lesions of 17 subjects were histologically proven to
      be malignant (papillary cancer in 16, metastasis from esophageal cancer in 1, non
      Hodgkin's lymphoma in 1). Therefore, the cancer risk of focal thyroid lesions was
      36.7% on a lesion-by-lesion basis or 38.6% on a subject-by-subject basis. The
      maximum SUV of malignant thyroid lesions was significantly higher than that of
      benign lesions (6.7 +/- 5.5 vs. 10.7 +/- 7.8; P < 0.05). When only the maximum
      SUV was applied to differentiate benign from malignant focal thyroid lesions for
      the receiver-operating-characteristic curve analysis, the area under the curve
      (AUC) of PET was 0.701. All 16 focal thyroid lesions with very low attenuation or
      nonlocalization on CT images, or with accompanying diffusely increased thyroid
      (18)F-FDG uptake, were benign. When those lesions were regarded as benign
      lesions, irrespective of the maximum SUV, the AUC of PET/CT was significantly
      improved to 0.878 (P < 0.01). CONCLUSION: Focal thyroid lesions incidentally
      found on (18)F-FDG PET/CT have a high risk of thyroid malignancy. Image
      interpretation that includes (18)F-FDG uptake and the CT attenuation pattern,
      along with the SUV, significantly improves the accuracy of PET/CT for
      differentiating benign from malignant focal thyroid lesions.

PMID- 16595495
TI  - Integrated PET/CT in differentiated thyroid cancer: diagnostic accuracy and
      impact on patient management.
AB  - The aim of this study was to investigate the diagnostic accuracy and impact on
      patient management of the new integrated PET/CT modality in patients with
      suspected iodine-negative, differentiated thyroid carcinoma (DTC). METHODS: Forty
      patients with DTC and a suggestion of iodine-negative tumor tissue underwent
      PET/CT examination (370 MBq (18)F-FDG, coregistered PET/CT whole-body images). As
      the first step of analysis, PET and CT images were scored blindly and
      independently by 2 nuclear medicine physicians and 2 radiologists. A 5-point
      scale was used. The second step consisted of a consensus reading, during which a
      virtual side-by-side fusion of PET and CT images was initially evaluated and
      afterward the "real" fusion (i.e., coregistered) PET/CT images were also scored
      with the same 5-point scale. The imaging results were compared with
      histopathologic findings and the course of disease during further follow-up
      examinations. RESULTS: One hundred twenty-seven lesions in 40 patients were
      evaluated. Diagnostic accuracy was 93% and 78% for PET/CT and PET, respectively
      (P = 0.049, per-patient analysis). In 17 (74%) of 23 patients with suspicious
      (18)F-FDG foci, integrated PET/CT added relevant information to the side-by-side
      interpretation of PET and CT images by precisely localizing the lesion(s). In
      tumor-positive PET patients, PET/CT fusion by coregistration led to a change of
      therapy in 10 (48%) patients. Futile surgery was prevented in an additional 3
      patients. CONCLUSION: Integrated PET/CT is able to improve diagnostic accuracy in
      a therapeutically relevant way in patients with iodine-negative DTC. By precisely
      localizing tumor tissue, image fusion by integrated PET/CT is clearly superior to
      side-by-side interpretation of PET and CT images.

PMID- 16595496
TI  - Imaging infection with 18F-FDG-labeled leukocyte PET/CT: initial experience in 21
      patients.
AB  - The aim of this study was to assess the feasibility and the potential role of
      PET/CT with (18)F-FDG-labeled autologous leukocytes in the diagnosis and
      localization of infectious lesions. METHODS: Twenty-one consecutive patients with
      suspected or documented infection were prospectively evaluated with whole-body
      PET/CT 3 h after injection of autologous (18)F-FDG-labeled leukocytes. Two
      experienced nuclear medicine physicians who were unaware of the clinical end
      diagnosis reviewed all PET/CT studies. A visual score (0-3)-according to uptake
      intensity-was used to assess studies. The results of PET/CT with (18)F-FDG
      labeled white blood cell ((18)F-FDG-WBC) assessment were compared with histologic
      or biologic diagnosis in 15 patients and with clinical end-diagnosis after
      complete clinical work-up in 6 patients. RESULTS: Nine patients had fever of
      unknown etiology, 6 patients had documented infection but with unknown extension
      of the infectious disease, 4 patients had a documented infection with unfavorable
      evolution, and 2 patients had a documented infection with known extension. The
      best trade-off between sensitivity and specificity was obtained when a visual
      score of >or=2 was chosen to identify increased tracer uptake as infection. With
      this threshold, sensitivity, specificity, and accuracy were each 86% on a patient
      per-patient basis and 91%, 85%, and 90% on a lesion-per-lesion basis. In this
      small group of patients, the absence of areas with increased WBC uptake on WBC
      PET/CT had a 100% negative predictive value. CONCLUSION: Hybrid (18)F-FDG-WBC
      PET/CT was found to have a high sensitivity and specificity for the diagnosis of
      infection. It located infectious lesions with a high precision. In this small
      series, absence of areas with increased uptake virtually ruled out the presence
      of infection. (18)F-FDG-WBC PET/CT for infection detection deserves further
      investigation in a larger prospective series.

PMID- 16595497
TI  - Dual-time-point 18F-FDG PET for the evaluation of gallbladder carcinoma.
AB  - Conventional imaging techniques such as ultrasonography, CT, and MRI are able to
      detect gallbladder abnormalities but are not always able to differentiate a
      malignancy from other disease processes such as cholecystitis. The purpose of the
      present study was to evaluate the efficacy of dual-time-point (18)F-FDG PET for
      differentiating malignant from benign gallbladder disease. METHODS: The study
      evaluated 32 patients who were suspected of having gallbladder tumors. (18)F-FDG
      PET (whole body) was performed at 62 +/- 8 min (early) after (18)F-FDG injection
      and was repeated 146 +/- 14 min (delayed) after injection only in the abdominal
      region. We evaluated the (18)F-FDG uptake both visually and semiquantitatively.
      Semiquantitative analysis using the standardized uptake value (SUV) was performed
      for both early and delayed images (SUV(early) and SUV(delayed), respectively).
      The retention index (RI) was calculated according to the equation (SUV(delayed) -
      SUV(early)) x 100/SUV(early). The tumor-to-liver ratio was also calculated.
      RESULTS: The final diagnosis was gallbladder carcinoma in 23 patients and benign
      disease in 9 patients. For visual analysis of gallbladder carcinoma, delayed
      (18)F-FDG PET images improved the specificity of diagnosis in 2 patients. When an
      SUV(early) of 4.5, SUV(delayed) of 2.9, and RI of -8 were chosen as arbitrary
      cutoffs for differentiating between malignant and benign conditions, sensitivity
      increased from 82.6% to 95.7% and 100% for delayed imaging and combined early and
      delayed imaging (i.e., RI), respectively. With the same criteria, specificity
      decreased from 55.6% to 44.4% for delayed imaging and combined early and delayed
      imaging, respectively. The specificity of (18)F-FDG PET improved to 80% in the
      group with a normal level of C-reactive protein (CRP) and decreased to 0% in the
      group with an elevated CRP level. For gallbladder carcinoma, both SUV and tumor
      to-liver ratios derived from delayed images were significantly higher than the
      ratios derived from early images (P < 0.0001). CONCLUSION: Delayed (18)F-FDG PET
      is more helpful than early (18)F-FDG PET for evaluating malignant lesions because
      of increased lesion uptake and increased lesion-to-background contrast. However,
      the diagnostic performance of (18)F-FDG PET depends on CRP levels.

PMID- 16595498
TI  - Performance test of an LSO-APD detector in a 7-T MRI scanner for simultaneous
      PET/MRI.
AB  - PET combined with CT has proven to be a valuable multimodality imaging device
      revealing both functional and anatomic information. Although PET/CT has become
      completely integrated into routine clinical application and also has been used in
      small-animal imaging, CT provides only limited soft-tissue contrast and, in
      preclinical studies, exposes the animal to a relatively high radiation dose.
      Unlike CT, MRI provides good soft-tissue contrast even without application of
      contrast agents and, furthermore, does not require ionizing radiation. METHODS:
      This project focused on combining a high-resolution PET scanner with a 7-T MRI
      system for animal research. Because classic PET detectors based on
      photomultiplier tubes cannot be used in high magnetic fields, we used a detector
      technology based on 10 x 10 lutetium oxyorthosilicate crystal arrays and 3 x 3
      avalanche photodiode arrays. A ring of such PET detectors will ultimately be used
      as an insert for the 119-mm-diameter MRI bore. RESULTS: Initial measurements with
      1 PET detector module in the 7-T field during application of MRI sequences were
      encouraging. Position profiles from the PET detectors and a first MR image of a
      mouse could be acquired simultaneously. CONCLUSION: Further work will concentrate
      on the construction of a full PET detector ring with compact, integrated
      electronics.

PMID- 16595499
TI  - Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer:
      procedures and results of a prospective international controlled study of
      ablation after rhTSH or hormone withdrawal.
AB  - Technical aspects and results of the dosimetric assessments of postoperative
      radioiodine ablation in the framework of an international, prospective,
      controlled, randomized, comparative study of the effectiveness of ablation
      therapy with 3.7 GBq (131)I in differentiated thyroid cancer after stimulation
      with recombinant human TSH (rhTSH) or by thyroid hormone withdrawal (THW) are
      presented. METHODS: Sixty-three patients were randomized after thyroidectomy to
      either the THW or the rhTSH group. Scintigraphic neck images were acquired
      starting 48 h after radioiodine administration to assess biokinetics in the
      thyroid remnant. The activity in blood samples was quantified and data from whole
      body probe measurements and scintigraphic whole-body scans were combined to
      deduce retention curves in blood and whole body, respectively. The absorbed dose
      to the blood was calculated using a modified approach based on the formalism of
      the MIRD Committee of the Society of Nuclear Medicine. RESULTS: The effective
      half-time in the remnant thyroid tissue was significantly longer after rhTSH than
      THW (67.6 +/- 48.8 vs. 48.0 +/- 52.6 h, respectively; P = 0.01), whereas the
      observed differences of the mean 48-h (131)I uptakes (0.5% +/- 0.7% vs. 0.9% +/-
      1.0% after THW; P = 0.1) and residence times (0.9 +/- 1.3 vs. 1.4 +/- 1.5 h after
      THW; P = 0.1) between the rhTSH and THW groups were not statistically
      significant. The specific absorbed dose to the blood was significantly (P
      <0.0001) lower after administration of rhTSH (mean, 0.109 +/- 0.028 mGy/MBq;
      maximum, 0.18 mGy/MBq) than after THW (mean, 0.167 +/- 0.061 mGy/MBq; maximum,
      0.35 mGy/MBq), indicating that higher activities of radioiodine might be safely
      administered after exogenous stimulation with rhTSH. CONCLUSION: Indication of an
      influence of the residence time of radioiodine in the blood on the fractional
      uptake into thyroid remnant was found. A novel regimen is proposed in which
      therapeutic activities to be administered are determined from the individual
      specific blood dose.

PMID- 16595500
TI  - Voxel-based mouse and rat models for internal dose calculations.
AB  - The ability to estimate absorbed doses in experimental animals to which
      radiolabeled material has been administered may be important in explaining and
      controlling potential radiation toxicity observed during preclinical trials. Most
      previously reported models for establishing doses to small animals have been
      stylized and mathematically based. This study establishes dose factors for
      internal sources in realistic models of a typical mouse and a typical rat, based
      on image data obtained using a dedicated small-animal CT scanner. METHODS: A
      transgenic mouse (body mass, 27 g) and a Sprague-Dawley rat (body mass, 248 g)
      were imaged using the dedicated small-animal CT scanner. Identified organs were
      segmented using computer tools that Vanderbilt University applies to process
      human images for 3-dimensional dosimetry. Monte Carlo N-particle transport code
      (MCNP) input files were prepared from the 3-dimensional, voxel-based image data.
      Using methods established for human studies, radiation transport calculations of
      absorbed fractions (AFs) were performed using MCNP, version 4C, on the segmented
      images, and dose conversion factors for several radionuclides were developed.
      RESULTS: AFs were established at discrete energies for electron and photon
      sources assumed to be uniformly distributed throughout approximately 10 source
      and target regions in both models. Electron self-irradiation AFs were
      significantly less than 1.0 for many organs, at energies above 0.5 MeV, and
      significant cross irradiation was observed for high-energy electrons, such as
      those from (90)Y or (188)Re, in many organs. Calculated dose conversion factors
      reflected these trends and agreed well with the results of other authors who have
      undertaken similar investigations. CONCLUSION: The AFs calculated in this study
      will be useful in determining the dose to organs for mice and rats similar in
      size to those studied here. The segmented, voxel-based models developed here can
      be used for external dose calculations as well.

PMID- 16595501
TI  - Potential increased tumor-dose delivery with combined 131I-MIBG and 90Y-DOTATOC
      treatment in neuroendocrine tumors: a theoretic model.
AB  - (131)I-Metaiodobenzylguanidine (MIBG) and (90)Y-DOTA-D-Phe1-Tyr3-octreotide
      (DOTATOC) have been used as radiotherapeutic agents for treating neuroendocrine
      tumors. The tumor dose delivered by these agents is often insufficient to control
      or cure the disease. However, these 2 agents used together could potentially
      increase tumor dose without exceeding the critical organ dose because the dose
      limiting tissues are different. In this paper, we investigate the conditions in
      which combined-agent therapy is advantageous and we quantify the expected tumor
      dose gain. METHODS: A series of equations was derived that predicted the optimal
      combination of agents and the fractional increase in tumor dose available from
      combined-agent therapy with respect to either (131)I-MIBG or (90)Y-DOTATOC. The
      results obtained from these derivations were compared with direct dose
      calculations using published dosimetric organ values for (131)I-MIBG and (90)Y
      DOTATOC along with critical organ-dose limits. Tumor dose was calculated as a
      function of the tumor-dose ratio, defined as the (90)Y-DOTATOC tumor dose per
      megabecquerel divided by the (131)I-MIBG tumor dose per megabecquerel.
      Comparisons were made between the dose delivered to tumor with single-agent
      therapy and the dose delivered to tumor with combined-agent therapy as a function
      of the tumor-dose ratio and the fraction of activity contributed by each agent.
      RESULTS: The dose model accurately predicted the optimal combination of agents,
      the range at which combined-agent therapy was advantageous, and the magnitude of
      the increase. For the published organ dosimetry and critical organ-dose limits,
      combined-agent therapy increased tumor dose when the tumor-dose ratio was greater
      than 0.67 and less than 5.93. The maximum combined-agent tumor-dose increase of
      68% occurred for a tumor-dose ratio of 2.57, using 92% of the maximum tolerated
      (90)Y-DOTATOC activity supplemented with 76% of the maximum tolerated activity of
      (131)I-MIBG. Variations in organ dose per megabecquerel and dose-limiting values
      altered both the magnitude of the increase and the range at which combined-agent
      therapy was advantageous. CONCLUSION: Combining (131)I-MIBG and (90)Y-DOTATOC for
      radiotherapy of neuroendocrine tumors can significantly increase the delivered
      tumor dose over the dose obtained from using either agent alone. Prior knowledge
      of the normal-organ and tumor dosimetry of both agents is required to determine
      the magnitude of the increase.

PMID- 16595502
TI  - Tumor targeting by an aptamer.
AB  - Aptamers are small oligonucleotides that are selected to bind tightly and
      specifically to a target molecule. We sought to determine whether aptamers have
      potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS:
      TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in
      fluorescent and radiolabeled forms. After in vivo administration, uptake and
      tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence
      microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor
      xenografts, biodistribution and imaging studies were performed using TTA1
      radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a
      variety of additional human tumor xenografts. To assess the effect of radiometal
      chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with
      diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG
      (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced
      bright perivascular fluorescence in a xenografted human tumor within 10 min. In
      the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with
      (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min,
      and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention
      was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1
      %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of
      50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the
      (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained
      by planar scintigraphy. Aptamer uptake, seen in several different human tumors,
      required the presence of the target protein, human tenascin-C. Modification of
      the MAG(2) radiometal chelator dramatically altered the uptake and clearance
      patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including
      breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance
      from the blood and other nontarget tissues enables clear tumor imaging. As
      synthetic molecules, aptamers are readily modified in a site-specific manner. A
      variety of aptamer conjugates accumulate in tumors, suggesting imaging and
      potentially therapeutic applications.

PMID- 16595503
TI  - Evaluation of D-isomers of O-11C-methyl tyrosine and O-18F-fluoromethyl tyrosine
      as tumor-imaging agents in tumor-bearing mice: comparison with L- and D-11C
      methionine.
AB  - The aim of this study was to investigate whether D-amino acid isomers of O-(11)C
      methyl tyrosine ((11)C-CMT) and O-(18)F-fluoromethyl tyrosine ((18)F-FMT) were
      better than the corresponding L-isomers as tumor- detecting agents with PET in
      comparison with the difference between L- and D-methyl-(11)C-methionine ((11)C
      MET). METHODS: L- and D-(11)C-MET, (11)C-CMT, and (18)F-FMT were injected
      intravenously into BALB/cA Jcl-nu mice bearing HeLa tumor cells. At 5, 15, 30,
      and 60 min after injection, normal abdominal organs and xenotransplanted HeLa
      cells were sampled, and the uptake of each ligand was determined. Metabolic
      analyses of these compounds in the plasma were also performed. Accumulation of
      the d-isomers of (11)C-MET, (11)C-CMT, and (18)F-FMT in turpentine-induced
      inflammatory tissue was assayed in comparison with (18)F-FDG. The whole-body
      distribution of each tracer was imaged with a planar positron imaging system
      (PPIS). RESULTS: Although the tumor uptake (standardized uptake value [SUV])
      levels of the D-isomers of (11)C-MET, (11)C-CMT, and (18)F-FMT were 261%, 72%,
      and 95% of each L-isomer 60 min after administration, the tumor-to-blood ratios
      of these D-isomers were 130%, 140%, and 182% of the corresponding L-isomers. In
      the blood, the D-isomers of these labeled compounds revealed a relatively faster
      elimination rate compared with their L-isomers, with a high peak uptake in the
      blood and kidney 5 min after administration. Compared with the natural amino acid
      ligand l-(11)C-MET, the uptake of L-isomers of (11)C-CMT and (18)F-FMT was
      relatively low and stable in the abdominal organs, whereas D-isomers revealed
      much lower levels and faster clearance rates compared with corresponding L
      isomers. Among the abdominal organs, the pancreas showed a relatively high uptake
      of (11)C-CMT and (18)F-FMT; the uptake of these D-isomers was much lower than
      that of L-isomers. Pretreatment with cycloheximide, a protein synthesis
      inhibitor, resulted in a marked reduction of L-(11)C-MET uptake and a slight
      reduction of D-(11)C-MET uptake into protein fractions, whereas no significant
      changes were detected with L- and D-(11)C-CMT and (18)F-FMT. D-Isomers of (11)C
      MET, (11)C-CMT, and (18)F-FMT did not accumulate in turpentine-induced
      inflammatory tissue, where (18)F-FDG revealed a high uptake. Whole-body imaging
      with a PPIS provided consistent distribution data obtained from the tissue
      dissection analysis. CONCLUSION: These results suggest that D-isomers of (11)C
      CMT and (18)F-FMT could be potentially better tracers than L- and D-(11)C-MET for
      tumor imaging with PET.

PMID- 16595504
TI  - Assessment of myocardial metabolism in diabetic rats using small-animal PET: a
      feasibility study.
AB  - This feasibility study was undertaken to determine whether kinetic modeling in
      conjunction with small-animal PET could noninvasively quantify alterations in
      myocardial perfusion and substrate metabolism in rats. METHODS: All small-animal
      PET was performed on either of 2 tomographs. Myocardial blood flow and substrate
      metabolism were measured in 10 male Zucker diabetic fatty rats (ZDF, fa/fa) and
      10 lean littermates (Lean, Fa/+) using (15)O-water, 1-(11)C-glucose, 1-(11)C
      acetate, and 1-(11)C-palmitate. Animals were 12.0 +/- 1.4-wk old. RESULTS:
      Consistent with a type 2 diabetic phenotype, the ZDF animals showed higher plasma
      hemoglobin A(1c), insulin, glucose, and free fatty acid (FFA) levels than their
      lean controls. Myocardial glucose uptake (mL/g/min) was not significantly
      different between the 2 groups. However, higher glucose plasma levels in the ZDF
      rats resulted in higher myocardial glucose utilization (nmol/g/min) (Lean, 629 +/
      785, vs. ZDF, 1,737 +/- 1,406; P = 0.06). Similarly, myocardial FFA uptake
      (mL/g/min) was not significantly different between the 2 groups, (Lean, 0.51 +/-
      28, vs. ZDF, 0.72 +/- 0.19; P = not significant) However, due to higher FFA
      plasma levels, utilization and oxidation (nmol/g/min) were significantly higher
      in the ZDF group (Lean, 519 +/- 462, vs. ZDF, 1,623 +/- 712, P < .001; and Lean,
      453 +/- 478, vs. ZDF, 1,636 +/- 730, P < .01). CONCLUSION: Noninvasive
      measurements of myocardial substrate metabolism in ZDF rats using small-animal
      PET are consistent with the expected early metabolic abnormalities that occur in
      this well-characterized model of type 2 diabetes mellitus. Thus, small-animal PET
      demonstrates significant promise in providing a means to link the myocardial
      metabolic abnormalities that occur in rat of disease with the human condition.

PMID- 16595505
TI  - Radiosynthesis and preclinical evaluation of 11C-ABP688 as a probe for imaging
      the metabotropic glutamate receptor subtype 5.
AB  - (11)C-ABP688 (3-(6-methyl-pyridin-2-ylethynyl)-cyclohex-2-enone-O-(11)C-methyl
      oxime), a noncompetitive and highly selective antagonist for the metabotropic
      glutamate receptor subtype 5 (mGluR5), was evaluated for its potential as a PET
      agent. METHODS: ABP688 was radiolabeled with (11)C by reacting (11)C-methyl
      iodide with the sodium salt of desmethyl-ABP688 (3-(6-methyl-pyridin-2-ylethynyl)
      cyclohex-2-enone oxime). The affinity of (11)C-ABP688 for mGluR5 was determined
      by Scatchard analysis using rat whole-brain membranes (without cerebellum). Ex
      vivo autoradiography, biodistribution, and PET studies with (11)C-ABP688 were
      performed on rats, wild-type mice, and mGluR5-knock-out mice. RESULTS: The
      overall synthesis time was 45-50 min from the end of radionuclide production.
      (11)C-ABP688 was obtained in good radiochemical yield (35% +/- 8%, n = 17, decay
      corrected), and the specific radioactivity was 150 +/- 50 GBq/mumol (n = 17) at
      the end of the synthesis. Scatchard analysis revealed a single high-affinity
      binding site with a dissociation constant of 1.7 +/- 0.2 nmol/L and a maximum
      number of binding sites of 231 +/- 18 fmol/mg of protein. Ex vivo autoradiography
      in wild-type mice and rats showed a heterogeneous distribution pattern consistent
      with the known distribution of mGluR5 in the brain, with the highest uptake in
      hippocampus, striatum, and cortex. Blocking studies by coinjection of (11)C
      ABP688 and unlabeled 2-methyl-6-(3-methoxyphenyl)ethynyl-pyridine (1 mg/kg), an
      antagonist for mGluR5, revealed up to 80% specific binding in rat brain. In
      mGluR5-knock-out mouse brain, a homogeneous and markedly reduced accumulation of
      (11)C-ABP688 was observed. PET studies on rats and mice using a small-animal PET
      scanner also demonstrated radioactivity uptake in the brain regions known to be
      rich in mGluR5. In contrast, radioactivity uptake in mGluR5-knock-out mice was
      fairly uniform, substantiating the specificity of (11)C-ABP688 binding to mGluR5.
      CONCLUSION: (11)C-ABP688 is a selective tracer for imaging mGluR5 in vivo in
      rodents and may offer a future tool for imaging mGluR5 in humans using PET.

PMID- 16595506
TI  - Preclinical safety evaluation of 18F-FHBG: a PET reporter probe for imaging
      herpes simplex virus type 1 thymidine kinase (HSV1-tk) or mutant HSV1-sr39tk's
      expression.
AB  - 9-(4-(18)F-Fluoro-3-[hydroxymethyl]butyl)guanine ((18)F-FHBG) is a sensitive and
      specific PET reporter probe for imaging the PET reporter genes, herpes simplex 1
      thymidine kinase (HSV1-tk) and its mutant HSV1-sr39tk. (18)F-FHBG has suitable
      pharmacokinetics and dosimetry for clinical applications and imaging of HSV1-TK
      has been demonstrated in the livers of hepatocellular cancer patients. METHODS:
      Male and female Sprague-Dawley rats and New Zealand White rabbits were divided
      into equal groups receiving either 14 microg/kg cold FHBG or carrier solution,
      for a 14-d acute toxicity assessment. We monitored body weight, food and water
      consumption, body temperature, cardiovascular electrical and functional indices,
      respiratory performance and oxygen saturation, comprehensive blood chemistry,
      complete blood count (CBC), and urinalysis. We conducted daily cage-side
      examinations for the detection of any clinical abnormalities. Tissues of the
      animals that were euthanized and necropsied on day 14 were prepared for
      histopathologic examination. RESULTS: No significant differences in
      cardiovascular and respiratory parameters, food consumption, body weight, urine
      components, or clinical signs attributable to test article toxicity were observed
      between the treatment and control groups. Any differences noted in the blood
      chemistry and CBC parameters were deemed to be incidental findings unrelated to
      the administration of the FHBG. CONCLUSION: Acute toxicity evaluation of FHBG at
      100 times the expected human dose does not indicate harm to organ function or
      tissues. The Food and Drug Administration has approved FHBG as an Investigational
      New Drug.

PMID- 16595507
TI  - Enhanced efficacy of 90Y-radiolabeled anti-Lewis Y humanized monoclonal antibody
      hu3S193 and paclitaxel combined-modality radioimmunotherapy in a breast cancer
      model.
AB  - Radioimmunotherapy (RIT) of solid tumor is often limited in efficacy because of
      restrictions in achieved tumor dose. In an effort to overcome this, the
      combination of RIT with other therapeutic modalities was investigated in an
      animal model of breast carcinoma. The rationale for this combined-modality RIT
      (CMRIT) was to increase the therapeutic efficacy of RIT through the use of
      paclitaxel to arrest cells in the radiosensitive G(2)/M phase of the cell cycle.
      METHODS: In this study, the biodistribution and therapeutic efficacy of (90)Y
      radiolabeled humanized anti-Lewis Y hu3S193 monoclonal antibody ((90)Y-hu3S193)
      RIT in combination with paclitaxel chemotherapy was explored in a Lewis Y
      expressing MCF-7 tumor xenografted BALB/c nude mouse model of breast cancer.
      RESULTS: Biodistribution studies demonstrated excellent tumor targeting and
      limited normal tissue uptake by (90)Y-hu3S193. A therapeutic study with
      established tumors assessed (90)Y-hu3S193 as a single agent and demonstrated
      significant antitumor effects in all animals receiving a single intravenous 1.85
      or 3.70 MBq dose of this treatment compared with phosphate-buffered saline
      placebo controls (P = 0.0008 vs. P < 0.0001). Complete responses were observed in
      all animals in the 3.70 MBq study arm for the duration of the study. Single-dose
      (90)Y-hu3S193 plus paclitaxel (600 microg) CMRIT displayed improved efficacy over
      single-modality therapies, with a significant difference (P < 0.0001) between the
      mean percentage change in tumor volume in mice receiving 0.46 MBq (90)Y-hu3S193
      alone and when combined with 600 mug paclitaxel. CONCLUSION: The significant
      efficacy of (90)Y-hu3S193 and paclitaxel CMRIT at low radiation doses in this
      model of breast carcinoma indicates its therapeutic potential and warrants
      further investigation into this promising therapeutic approach.

PMID- 16595511
TI  - Advantage of late scanning in brain 18F-FDG PET.

PMID- 16595513
TI  - Dendritic cells pulsed with apoptotic cells activate self-reactive T-cells of
      lupus mice both in vitro and in vivo.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) is characterized by the presence
      of autoantibodies (autoAbs) directed against the nuclear structure. Previous
      studies have demonstrated that dendritic cells (DCs) can process and present self
      antigens (Ags) from apoptotic cells (ACs) in lupus. However, there is no direct
      evidence demonstrating that ACs provide self-Ags, such as histones, to stimulate
      autoreactive T-cells in lupus. METHODS: AC-pulsed bone marrow-derived DCs (AC
      BMDCs) were used to stimulate autoreactive T-cells in vitro and in vivo. RESULTS:
      In our study, we found that AC-BMDCs could induce the proliferation of CD4+ T
      cells from unprimed NZB x NZW F1 (BWF1) mice, which spontaneously develop SLE,
      but not CD4+ T-cells, from non-autoimmune DBA-2 x NZW F1 (DWF1) mice. In
      addition, AC-BMDCs could induce significant proliferative responses to certain
      histone peptide-specific T-cells. Furthermore, these AC-BMDCs could induce a
      considerable anti-DNA Ab response in vivo after adoptive transfer into DWF1 mice,
      suggesting that AC-BMDCs can break tolerance in normal mice and initiate an
      autoimmune response. CONCLUSION: Our study provides a direct link between self
      epitopes from ACs presented by DCs and autoreactive T-cell activation, and
      demonstrates that ACs are critical for the induction of autoimmunity in vivo.

PMID- 16595514
TI  - Disease and psychological status in ankylosing spondylitis.
AB  - OBJECTIVES: Psychological factors may be important in the assessment and
      management of ankylosing spondylitis (AS). Our primary objective was to describe
      associations between disease and psychological status in AS, using AS-specific
      assessment tools and questionnaires. Our secondary objectives were to identify
      patient subgroups based on such associations and to determine the stability of
      the measures over time. METHODS: A total of 110 patients were assessed at 6
      monthly intervals up to four times using tools to measure disease [Bath
      Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing
      Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis
      Metrology Index (BASMI)], psychological [Hospital Anxiety and Depression
      Questionnaire (HADS), Health Locus of Control-Form C Questionnaire (HLC-C)] and
      generic health [Short form (SF)-36] status. RESULTS: Eighty-nine participants
      completed all four assessments. Throughout the study, BASDAI, BASFI and BASMI
      scores correlated significantly with anxiety, depression, internality and health
      status, but not with levels of belief in chance or powerful others. Clinically
      anxious or depressed subgroups had significantly worse BASDAI and BASFI, but not
      BASMI, scores. BASMI scores were the least closely linked to psychological
      status. Mean scores for disease, psychological and health status were clinically
      stable over the 18 months period. CONCLUSIONS: Disease status scores in AS
      correlated significantly with anxiety, depression, internality and health status.
      Interpretation of AS disease scores should take an account of psychological
      status and the choice of measures used. These findings have important potential
      applications in AS management and monitoring, including the identification of
      patients for biological therapies.

PMID- 16595515
TI  - Impaired reproductive fitness in mothers of children with juvenile autoimmune
      arthropathies.
AB  - OBJECTIVE: To assess the reproductive fitness of mothers of children with
      juvenile idiopathic arthritis (JIA). METHODS: A mail survey assessing pregnancy
      outcome was carried out among mothers of children with JIA (JIA mothers) treated
      at a tertiary paediatric rheumatology centre. The best friends of the JIA mothers
      served as controls. Besides family history, sociodemographics and reproductive
      outcomes were measured, including the number of pregnancies, pregnancy
      complications and gestational age at the time of delivery. RESULTS: JIA mothers
      (n = 227) and controls (n = 235) had similar sociodemographics and racial
      backgrounds. On average, JIA mothers reported a greater number of conceptions
      than controls (3.5 vs 3.1; P = 0.01) but had significantly higher rates of
      pregnancy complications (25% vs 15%; P<0.001). Corrected for differences in the
      absolute number of pregnancies between groups, the chances of having a
      miscarriage [mean (s.d.), 0.12 (0.18) vs 0.09 (0.16); P = 0.02] or preterm
      delivery [0.08 (0.21) vs 0.04 (0.15); P<0.02] were significantly greater among
      JIA mothers than controls. CONCLUSIONS: Mothers of children with JIA have
      impaired reproductive fitness. This phenomenon is unlikely to be the result of
      difficulty with conception but rather to be due to higher rates of pregnancy loss
      and premature delivery.

PMID- 16595516
TI  - Polyarteritis nodosa when applying the Chapel Hill nomenclature--a descriptive
      study on ten patients.
AB  - OBJECTIVES: Polyarteritis nodosa (PAN) is a term that has been used to describe a
      wide variety of vasculitic conditions. In 1994, the Chapel Hill Consensus
      Conference on the nomenclature of systemic vasculitides proposed that the name
      classical PAN should be restricted to diseases where there is arteritis in small
      and medium-sized arteries without the involvement of smaller vessels. Our aim was
      to describe the symptoms and course of disease in PAN when the microscopic forms
      are excluded. METHODS: All patients with a diagnosis of PAN treated in our
      departments during the period 1990-2002 were eligible for this study. The
      diagnosis had to be confirmed by biopsy, angiography or electromyography.
      RESULTS: Ten patients were eligible for the study. The median age was 46 yrs.
      Renal involvement was seen in 70% at diagnosis. After 5 yrs, 57% had experienced
      a relapse, which is equivalent to the relapse rate seen in microscopic
      polyangiitis. Organ damage was assessed by the Vasculitis Damage Index (VDI) and
      after 5 yrs cardiovascular and neuropsychiatric damage dominated, followed by
      renal damage. During the follow-up, two patients developed end-stage renal
      disease. The annual incidence of PAN in our local catchment area was estimated to
      1.6 per million and year. CONCLUSIONS: When applying the Chapel Hill
      nomenclature, PAN is a rare but severe disease with a high incidence of renal
      involvement and frequent relapses.

PMID- 16595519
TI  - Positive and negative predictive values from published studies can be misleading
      for decision-making in clinical practice.

PMID- 16595520
TI  - Sjogrens syndrome--the non-apoptotic model of glandular hypofunction.

PMID- 16595521
TI  - Quantitative ultrasonometry of the calcaneus in children with juvenile idiopathic
      arthritis.
AB  - OBJECTIVES: To evaluate bone quality by means of quantitative ultrasonometry
      (QUS) in children with juvenile idiopathic arthritis (JIA). METHODS: Seventy
      children [37 with oligoarticular JIA, mean age (+/-s.d.) 10.54 +/- 3.42 yr; and
      33 with polyarticular rheumatoid factor negative JIA, mean age (+/- s.d.) 11.33
      +/- 2.88 yr] were enrolled. Quantitative ultrasonometry was measured on both
      heels with a Cuba Clinical portable device. Body height, weight and body mass
      index were recorded together with disease duration and cumulative dose of
      prednisone. RESULTS: The lowest QUS parameters were observed in children with
      polyarticular JIA (P< 0.001 and 0.01 when compared with reference data and
      oligoarticular JIA, respectively). In children with oligoarticular JIA, the QUS
      values were also significantly lower in comparison with the reference data (P<
      0.002). The QUS parameters were strongly influenced by body height, and to a
      lesser degree by body weight. In children with polyarticular JIA, there were
      significant inverse correlations between QUS parameters and disease duration [r=
      0.57, P< 0.01 for broadband ultrasound attenuation (BUA) and r = - 0.67, P< 0.01
      for velocity of sound (VOS)]. Similarly, there were inverse correlations between
      QUS and cumulative dose of prednisone (r = - 0.48, P< 0.05 for BUA and r =- 0.50,
      P < 0.01 for VOS, respectively). Similar results were obtained when BUA and VOS
      were adjusted for height. CONCLUSIONS: Disease duration and cumulative dose of
      prednisone in children with polyarticular JIA are risk factors of stunted growth
      and decreased QUS values of bone quality.

PMID- 16595522
TI  - Adrenomedullin--a potential disease activity marker and suppressor of nephritis
      activity in systemic lupus erythematosus.
AB  - OBJECTIVES: To investigate whether plasma adrenomedullin (AM) level is elevated
      in lupus nephritis and to examine if plasma AM level is correlated with systemic
      lupus erythematosus (SLE) disease activity and severity of lupus nephritis after
      multivariate adjustment. METHODS: Consecutive SLE patients and healthy volunteers
      of age >/=16 were recruited from the rheumatology clinics of two hospitals in
      Hong Kong. SLE patients with nephritis fulfilled the American College of
      Rheumatology criteria for renal involvement and had percutaneous renal biopsy
      performed. Subjects were divided into three groups: (i) SLE patients with
      nephritis, (ii) SLE patients without nephritis and (iii) normal controls. The
      demographic and clinical variables were compared between these groups of patients
      and plasma AM level was determined by radioimmunoassay. Factors associated with
      plasma AM level were explored by regression analysis with adjustment of
      confounding factors. RESULTS: Sixty SLE patients (39 with nephritis and 21
      without) and 23 normal subjects were studied. The plasma AM level of SLE patients
      was significantly higher than that of normal controls. SLE patients with
      nephritis had significantly higher plasma AM level than those without nephritis
      and normal controls (P<0.001). In regression analysis, proteinuria was negatively
      associated with plasma AM level (P=0.006) whereas SLE disease activity index was
      positively associated with plasma AM level after multivariate adjustment
      (P=0.002). CONCLUSIONS: Plasma AM is elevated in lupus nephritis, which
      correlates with lupus disease activity. It is negatively associated with urine
      protein excretion although it is unrelated to the type of renal pathology per se.
      Plasma AM may play a role to suppress the activity of lupus nephritis.

PMID- 16595524
TI  - The Belgian Improvement Study in Oral Anticoagulant Therapy: a randomized
      clinical trial.

PMID- 16595523
TI  - Interleukin-8: more on the mechanisms of progenitor cells mobilization in acute
      coronary syndromes.

PMID- 16595525
TI  - Sleep is more than a break from life.

PMID- 16595526
TI  - Effect of antibiotic treatment of subclinical mastitis on human immunodeficiency
      virus type 1 RNA in human milk.
AB  - Although subclinical mastitis is associated with increased HIV load in breast
      milk, it is not known whether empirical treatment with antibiotics will reduce
      breast milk HIV load. We examined the effect of antibiotic treatment for
      subclinical mastitis on HIV load in breast milk. Seventy-five HIV-infected post
      partum women in Malawi with subclinical mastitis were treated with oral
      amoxicillin/clavulanic acid and were followed between 1 and 24 weeks later.
      Breastmilk HIV-1 load and sodium concentration were measured and microbiological
      studies were performed at presentation. At 1 week (n = 34), the proportion of
      women with elevated breast milk leukocyte counts decreased significantly to 41.2%
      (p < 0.0001) and there was a nonsignificant increase in breast milk HIV-1 RNA
      load (p = 0.9264) and sodium concentration (p = 0.08) in the affected breast. At
      4 to 12 weeks (n = 63), breast milk HIV-1 RNA load and sodium concentration
      decreased significantly (p < 0.05) and 17.5% had elevated breast milk leukocyte
      counts. Treatment with amoxicillin/clavulanic acid was associated with a
      significant decrease in inflammation of the breast, but breast milk HIV load
      remained elevated despite a significant decrease from baseline. These findings
      have important implications regarding how mothers should be counselled on safety
      of resuming breastfeeding after resolution of subclinical mastitis.

PMID- 16595527
TI  - How much basic science should be taught? The discussion continues.

PMID- 16595528
TI  - Oral pathology in the dental curriculum: a guide on what to teach.
AB  - There has been considerable disagreement among educators on the topics and
      details of topics that should be included in the teaching of oral pathology to
      dental students and graduate students in dental specialties. Various authorities
      have recommended core curricula that range from comprehensive teaching of
      eighteen categories, each with up to nine subheadings, covering hundreds of
      entities, to as few as approximately fifty of the most common lesions that affect
      the oral and maxillofacial region. This article offers a curriculum planning
      model designed to help faculty make decisions about course content and emphases.
      The model allows instructors to assess content relevance and priority based on
      three criteria: 1) commonness, 2) uniqueness, and 3) significance of diseases and
      conditions. The product of this decision-making process is a relevance score that
      can serve as a guideline for the choice and details of topics to be included in
      oral pathology courses.

PMID- 16595529
TI  - North American dental students' perspectives about their clinical education.
AB  - Many North American dental schools face the challenge of replacing the majority
      of their "boomer generation" clinical instructors over the next ten years as this
      cohort of faculty reaches retirement age. Developing a new cadre of clinical
      instructors poses a substantial faculty development challenge: what instructional
      techniques should be integrated into routine educational practice by the dental
      faculty of the future, and what aspects of the clinical learning environment
      should be addressed to improve the overall quality of the experience for
      patients, students, and the new cohort of instructors? To gain insight that might
      guide faculty development for new clinical instructors and enhance understanding
      of the learning environment in dental school clinics, this study addressed the
      following question: what are dental students' perceptions of their learning
      experiences in the clinical setting? The purpose of the study was to evaluate the
      effectiveness of the clinical instruction from the perspectives of the actual
      "consumer" of dental education: the student. This consumers' perspective was
      provided by 655 junior, senior, and graduate dental students at twenty-one North
      American dental schools who completed the Clinical Education Instructional
      Quality Questionnaire (ClinEd IQ) in 2003-04. The ClinED IQ examines four
      components of students' clinical experiences: 1) clinical learning opportunities,
      2) involvement in specific learning activities, 3) interaction with clinical
      instructors, and 4) personal perceptions about clinical education. With the
      exception of inconsistent feedback and instruction and lack of continuous contact
      with the same instructors, juniors, seniors, and graduate students rated their
      interaction with clinical instructors favorably (mean=4.76 on a 6.00 scale), but
      provided lower ratings for clinical learning opportunities (mean=4.26 on a 6.00
      scale) due to concerns about the efficiency of the dental clinic environment and
      lack of opportunity to treat patients in a variety of clinical settings. Analysis
      of more than 1,000 written comments provided by these students indicated four
      areas of concern: 1) inconsistent and sometimes insensitive (patronizing, rude)
      feedback from faculty; 2) excessive amounts of noneducational "legwork" such as
      billing, patient scheduling, phone calling, completing paperwork, and performing
      other clinic operations tasks; 3) limited access to faculty because of
      insufficient numbers of instructors on the clinic floor or difficulty locating
      faculty when they were needed for coaching, work evaluation, and chart
      signatures; and 4) concerns about the strategies employed to meet procedural
      requirements that some students saw as ethically questionable. Junior, senior,
      and graduate dental students at twenty-one North American dental schools
      perceived that the strongest aspect of their clinical education was their
      relationship with the faculty, but also reported that the dental school clinic
      was often an inefficient learning environment that hindered their opportunity to
      develop clinical competency. Students also sensed that faculty shortages, a
      growing crisis for dental education, hindered their progress in the clinic and
      made learning less efficient.

PMID- 16595531
TI  - Application of an interactive computer program to manage a problem-based dental
      curriculum.
AB  - Managing the change from traditional to problem-based learning (PBL) curricula is
      complex because PBL employs problem cases as the vehicle for learning. Each
      problem case covers a wide range of different learning issues across many
      disciplines and is coordinated by different facilitators drawn from the school's
      multidisciplinary pool. The objective of this project was to adapt an interactive
      computer program to manage a problem-based dental curriculum. Through application
      of a commercial database software--CATs (Curriculum Analysis Tools)--an
      electronic database for all modules of a five-year problem-based program was
      developed. This involved inputting basic information on each problem case
      relating to competencies covered, key words (learning objectives), participating
      faculty, independent study, and homework assignments, as well as inputting
      information on contact hours. General reports were generated to provide an
      overview of the curriculum. In addition, competency, key word, manpower, and
      clock-hour reports at three levels (individual PBL course component, yearly, and
      the entire curriculum) were produced. Implications and uses of such reports are
      discussed. The adaptation of electronic technology for managing dental curricula
      for use in a PBL curriculum has implications for all those involved in managing
      new-style PBL dental curricula and those who have concerns about managing the PBL
      process.

PMID- 16595530
TI  - Correcting for guessing increases validity in multiple-choice examinations in an
      oral and maxillofacial pathology course.
AB  - A standard correction for random guessing on multiple-choice examinations was
      examined retrospectively in an oral and maxillofacial pathology course for second
      year dental students. The correction was a weighting formula for points awarded
      for correct answers, incorrect answers, and unanswered questions such that the
      expected value of the increase in test score due to guessing was zero. We
      compared uncorrected and corrected scores on examinations using a multiple-choice
      format with scores on examinations composed of short-answer questions. The short
      answer format eliminated or at least greatly reduced the potential for guessing
      the correct answer. Agreement of corrected multiple-choice scores with short
      answer scores (intraclass correlation coefficient 0.78) was significantly
      (p=0.015) higher than agreement of uncorrected multiple-choice scores with short
      answer scores (intraclass correlation coefficient 0.71). The higher agreement
      indicated increased validity for the corrected multiple-choice examination.

PMID- 16595532
TI  - Dental education and care for underserved patients: an analysis of students'
      intentions and alumni behavior.
AB  - The U.S. surgeon general's report on oral health stressed the importance of
      providing dental care to underserved patients. The objectives of this study were
      to explore a) dental students' intentions and dentists' behavior concerning
      treating underserved patients, b) their perceptions of their education concerning
      these patients, and c) the relationship between dental education and their
      attitudes and behavior. Data were collected from 328 dental students (response
      rate: 77.5 percent) and 234 alumni (response rate: 43.7 percent). Only 67.4
      percent of the students and 38 percent of the alumni indicated that their
      education had prepared them well to treat patients from different socioeconomic
      backgrounds; 71.3 percent of students and 55.2 percent of alumni responded that
      they had been well educated to treat patients from different ethnic/racial
      groups. The findings showed a positive relationship between the degree of
      curriculum focus on the importance of treating patients from all aspects of
      society and students' and alumni intentions to provide inclusive patient care to
      patients from diverse backgrounds. The more students agreed that their dental
      education had prepared them well to treat patients from different ethnic
      backgrounds, the more likely they were to report that they intended to treat
      these patients (r=.12; p=.033). In a similar manner, the more the alumni agreed
      that their dental education had prepared them well to treat patients in different
      communities, the more likely they were to treat patients from different
      socioeconomic backgrounds (r=.18; p=.009). In conclusion, these findings showed
      that access to oral health care for underserved patients could potentially be
      increased if dental students were more overtly educated about the importance of
      treating patients from all segments of society.

PMID- 16595533
TI  - Promoting interpersonal skills and cultural sensitivity among dental students.
AB  - This study evaluated interpersonal communication skills among third- and fourth
      year dental students during two clinical communications training programs.
      Students participated in two clinical communications (CC) training sessions, each
      comprised of four encounters with patient instructors (PIs) who were trained to
      enact standardized patient scenarios. Scenarios in CC1 addressed straightforward
      patient care situations in dentistry (e.g., bridge adjustment), while CC2 added
      cultural sensitivity issues to the dental scenarios. After each encounter,
      patient instructors used the Arizona Clinical Interviewing Rating Scale (ACIR) to
      rate the students' interpersonal skills and gave the students feedback on their
      performance. The students also received feedback and coaching from dental school
      faculty in debriefings after encounters with the PIs. Students anonymously rated
      the program at the end of each session. To evaluate the program, students'
      performance was compared within and between the two training sessions. Analysis
      showed statistically significant increases in interpersonal communication skills
      within each training session (p<0.05) from unsatisfactory to above satisfactory
      levels. Performance scores at the start of CC2 were statistically lower than at
      the end of CC1, suggesting that performance wanes without practice. Student
      evaluations of the program were very positive. Interpersonal communication skills
      improved during this patient instructor program.

PMID- 16595534
TI  - A preliminary survey of interprofessional education.
AB  - The purpose of this article is to review the literature on interprofessional
      education (IPE) and report on a preliminary survey of the current status of
      interprofessional education in seven academic health centers (AHCs) that have
      schools of dentistry associated with them. There is wide variability in
      interpretation of the term "interprofessional," and many barriers to
      interprofessional education exist including already overcrowded curricula in
      health professions schools, lack of support from faculty and administration, and
      financial constraints. Based on interviews completed at the authors' home
      institutions, it was recommended that topics such as ethics, communication
      skills, evidence-based practice, and informatics could be effectively taught in
      an interprofessional manner. Currently, some academic health centers are
      attempting to develop interprofessional education programs, but most of these
      efforts do not include dental students. Of the seven AHCs investigated in this
      study, only two had formal interprofessional educational activities that involved
      students from two or more health professions education programs. Dental school
      participants in this study professed a strong interest in interprofessional
      programs, but many interviewees from other professional schools and AHC
      administrators perceived that the dental school was isolated from other schools
      and disinterested in IPE. Many health care setting models in the future will
      include dentists as part of an interdisciplinary health care team; consequently,
      it is important for dental schools to become an active participant in future
      interprofessional educational initiatives.

PMID- 16595535
TI  - Rater reliability: short- and long-term effects of calibration training.
AB  - The purpose of this investigation was to evaluate the immediate effects of
      calibration on inter-rater agreement to a gold standard (GS) and to determine
      whether the effects can be sustained over a ten-week period. Valid criteria for a
      Class II amalgam preparation, a three-point rating scale, and a grade form were
      developed. Three tests were administered: prior to calibration training,
      immediately following training, and ten weeks later. Each test consisted of
      faculty independently evaluating ten prepared teeth. Agreement with GS scores for
      most of the grading criteria improved as a result of training and did not
      deteriorate over time. The overall percent agreement was 54.5, 66.9, and 64.6
      percent across test periods. The most impressive gains in agreement occurred when
      the criteria evaluated had a GS score of either "standard not met" or "ideal."
      There was very little gain when the gold standard score was "acceptable." It is
      concluded that, with training, inter-rater agreement with a gold standard can
      improve and such improvement is reasonably resistant to deterioration after ten
      weeks. Nevertheless, future training ought to consider the use of a mastery
      approach in calibration training to ensure that a satisfactory degree of
      agreement with the GS is obtained.

PMID- 16595536
TI  - Hypertension in children: an overview.
AB  - Hypertension in children is an increasing concern for health care professionals.
      Updated guidelines for the treatment of hypertension in children and adolescents
      were published in 2004. This report reviews the epidemiology and management of
      pediatric hypertension and suggests an oral health protocol to apply to
      hypertensive children in the dental setting. A web search was performed using
      Medline, PubMed, ISI Citation Index, and Cochrane evidence-based databases for
      articles regarding hypertension in children published in English between 1998 and
      2004. Relevant articles describing the epidemiology, classification,
      pathophysiology, and management of pediatric hypertension are discussed, and
      recommendations for dental treatment of pediatric patients are suggested. The
      incidence of pediatric hypertension can reach 5 percent. Data on the prevalence
      of pediatric hypertension in the dental setting is scarce. However, using the
      prevalence in the general population, at least fifty young patients will be
      hypertensive in a busy general or pediatric practice. Dental students and
      residents should have the opportunity to screen for hypertension during their
      training and familiarize themselves with the appropriate techniques in children.
      Oral health professionals should become aware of the implications of hypertension
      in children.

PMID- 16595537
TI  - Principal dental admissions officers: Who are dentistry's gatekeepers?
AB  - Little is known about principal dental admissions officers (PDAO) in U.S. dental
      schools who may be viewed as the gatekeepers to our schools. To address this gap,
      this study examined the characteristics of PDAOs in U.S. dental schools. A web
      based, fifty-five-question survey on the personal and professional
      characteristics, roles, areas of responsibilities, and areas considered of
      importance to PDAOs was sent to fifty-six principal dental admissions officers at
      U.S. dental schools, followed by telephone calls to encourage participation.
      Thirty-eight PDAOs responded. The typical PDAO was Caucasian, fifty-two years of
      age, and had been in the position about eight years, earning dollar 80,000
      annually. Most supervised one or more employees and spent time working for the
      school outside the admissions process. Student contact activity considered most
      important was counseling prospective students, while maintaining health and
      financial records was considered unimportant. Minority recruitment efforts were
      considered highly important by a majority of PDAOs. The PDAOs have varied
      educational backgrounds and positions, but perform functions primarily dedicated
      to admissions.

PMID- 16595538
TI  - ADEA survey of clinic fees and revenue: 2003-04 academic year.
AB  - The American Dental Education Association's 2003-04 Survey of Clinic Fees and
      Revenue obtained data by which to report, by school, clinic revenue information
      per student. Fifty-one of the fifty-four dental schools that had third- and
      fourth-year students responded to the survey. The median revenue per third-year
      student was dollar 9,937. It was dollar 13,602 for fourth-year students. Clinic
      revenue was also obtained for programs of advanced dental education. General
      Practice Residency programs generated the highest revenue per student at dollar
      66,474, followed by programs of Advanced Education in General Dentistry at dollar
      63,860. Other areas of the survey provided information regarding clinic fees by
      type of program, levels of uncompensated care by type of program, clinic revenue
      by source of payment, and dental school fees as a percent of usual and customary
      private practice fees.

PMID- 16595539
TI  - Views of family physicians in southwestern Ontario on preventive care services
      and performance incentives.

PMID- 16595540
TI  - Methods for analysing recurrent events in health care data. Examples from
      admissions in Ebeltoft Health Promotion Project.
AB  - BACKGROUND: Evaluation of health care contacts from first events alone often
      misses large amounts of potentially important data and may produce different
      results than evaluation of all data including recurrent events. OBJECTIVE: We aim
      to bring the different methodological approaches for analysing longitudinal
      health care data to the attention of researchers in primary care. METHODS: We
      used hospital admission data from the Ebeltoft Health Promotion Project, a
      randomized trial in primary care examining the effect of preventive health
      checks. Comparisons included three randomized groups: an intervention group
      receiving health checks, a group where intervention consisted of a health check
      followed by a health discussion with the GP and one control group. RESULTS: Both
      intervention groups had approximately 20% fewer hospital admissions than the
      control group over a 6 year period. If dependence among recurrent events is
      excluded, such a reduction amounts to a highly significant effect. Use of the
      standard Poisson distribution for analysing recurrent events and exclusion of
      their dependent structure causes data interpretation to be incorrect, because the
      model does not account for the extra variability between persons; the resulting
      95% CIs would therefore be too small. CONCLUSION: Analysis of health care
      contacts should embrace both first and recurrent events and it should use a model
      appropriate to these data. An individual rate model that includes a parameter of
      an unspecified individual event distribution frailty may be a natural choice when
      analysing longitudinal data of contacts to the health care system in broad terms.

PMID- 16595542
TI  - Discussing partner abuse: does doctor's gender really matter?
AB  - BACKGROUND: There are conflicting findings on the influence of gender on
      responding to partner abuse. OBJECTIVES: We aimed to explore gender differences
      in family doctors' views, attitudes, experiences and practices regarding intimate
      partner abuse against women. METHODS: We used the focus-group method with a
      stratified, randomized sample of family physicians. Three male and three female
      groups took part. Two independent researchers analysed the transcripts of the
      discussions. RESULTS: There were differences between male and female groups in
      discussing partner abuse, although similarities were also noted. Major contrasts
      in opinions were seen in (i) the role of sexuality: part of the male family
      doctors stated that denial of sexual relationships by a spouse was a contributing
      and eliciting factor to male aggression, whereas female doctors emphasized
      unanimously the humiliation of sexual coercion and the danger of opposing. (ii)
      Children as witnesses: this issue was discussed in female groups only, (iii)
      female doctors talked about emotional involvement with patients and male doctors
      about keeping distance, (iv) female doctors viewed leaving an abusive partner as
      a process whilst male doctors saw no progress, (v) experiences with abused
      patients: female doctors remembered more actual cases and (vi) practices in
      managing partner abuse differed between men and women. CONCLUSION: These
      remarkable gender-related differences among doctors might affect care for abused
      women. Doctors should be aware of gender-related views, attitudes and practices
      that can be harmful to their patients.

PMID- 16595543
TI  - 'Two sides of the coin'--the value of personal continuity to GPs: a qualitative
      interview study.
AB  - BACKGROUND: Continuity is thought to be important to GPs but the values behind
      this are unknown. OBJECTIVES: To explore the values that doctors working in
      general practice attach to continuity of patient care and to outline how these
      values are applied in practice. METHODS: In-depth qualitative interview with 24
      GPs in England. Participants were purposefully sampled according to personal and
      practice characteristics. Analysis was thematic, drawing on the constant
      comparative method. RESULTS: The majority of doctors valued doctor-patient, or
      personal, continuity in their everyday work. It was most valued in patients with
      serious, complex or psychological problems. GPs believed that through their
      personal knowledge of the patient and the doctor-patient relationship, personal
      continuity enabled them to provide higher quality care. However, the benefits of
      personal continuity were balanced against problems, and GPs identified personal,
      professional and external constraints that limited its provision. GPs seemed to
      have resolved the tension between the benefits, limits and constraints they
      described by accepting an increased reliance on continuity being provided within
      teams. CONCLUSION: Personal continuity may offer important benefits to doctors
      and patients, but we do not know how unique its values are. In particular, it is
      not clear whether the same benefits can be achieved within teams, the level at
      which continuity is increasingly being provided. The relative advantages and
      limits of the different means of delivering continuity need to be better
      understood, before further policy changes that affect personal continuity are
      introduced.

PMID- 16595541
TI  - Asymptomatic bacteriuria in a population of elderly residents living in a
      community setting: prevalence, characteristics and associated factors.
AB  - BACKGROUND: Asymptomatic bacteriuria (ASB) is common among the elderly in
      institutional care, but less is known about its prevalence among the elderly
      living in community settings. Knowledge of the prevalence of ASB in this
      population could contribute to a reduction in unnecessary use of antibiotics.
      OBJECTIVE: To study the prevalence of ASB and associated health and social
      factors in a population of elderly people, aged 80 and over, in a community
      setting. DESIGN: A cross-sectional study. SETTING: The catchment area of a
      primary health care centre in a Swedish middle-sized town. METHOD: All residents,
      aged 80 and over, except for those in institutional living, were invited. A
      structured interview was carried out and urinary culture obtained. RESULTS: ASB
      was found in 14.8% of the participants, in 19.0% of the women and 5.8% of the
      men. In women independent associations with ASB were found for urinary
      incontinence (OR: 2.99, CI: 1.60-5.60), reduced mobility (OR: 2.68, CI: 1.42
      5.03) and oestrogen treatment (OR: 2.20, CI: 1.09-4.45). CONCLUSION: Bacteriuria
      is common among the elderly living in non-institutional community settings,
      especially among women, although not as common as among the elderly in
      institutional settings. A woman over 80, with urinary incontinence, and needing
      support to walk has a risk of nearly 50% of presenting with ASB, a condition
      about which there is consensus not to treat with antibiotics. This should be
      borne in mind when examining patients with diffuse symptomatology and an
      accidental finding of bacteriuria.

PMID- 16595544
TI  - The course of post-disaster health problems of victims with pre-disaster
      psychological problems as presented in general practice.
AB  - BACKGROUND: Survivors of disaster with pre-disaster psychological problems are
      believed to be at risk for presenting post-disaster psychological and physical
      morbidity. Up till now this statement is based on cross-sectional studies with
      self-reported data and without pre-disaster measurement. OBJECTIVE: To monitor
      post-disaster health care utilization and morbidity presented in general practice
      after a man-made disaster by victims and controls with and without pre-disaster
      psychological problems. METHODS: A controlled cohort study with pre-disaster (1
      year) and post-disaster (two-and-a-half years) data. Victims (N = 2518) of an
      exploding fireworks depot in a residential area and matched controls (N = 2512),
      representing patients in 30 general practices, were included. Main outcome
      measures were utilization measured by GP attendances, and psychological and
      physical problems registered by the GP using the International Classification of
      Primary Care. RESULTS: Only victims without pre-disaster psychological problems
      demonstrated a significant increase in utilization in the first half year post
      disaster. Victims with pre-disaster psychological problems did not. Being a
      victim (OR = 6.13; 95% CI = 4.84-7.77) had a greater effect than pre-disaster
      psychological problems (OR = 4.96; 95% CI = 3.96-6.21) on presenting post
      disaster psychological problems. Pre-disaster psychological problems had more
      effect (OR = 1.93; 95% CI = 1.79-2.08) than the effect of being a victim (OR =
      1.25; 95% CI = 1.18-1.32) on the development of post-disaster physical symptoms.
      CONCLUSION: Post-disaster increases in utilization and psychological morbidity
      were observed. Post-disaster psychological problems were more influenced by the
      disaster, while post-disaster physical symptoms were more influenced by pre
      disaster psychological problems. GPs should concentrate on the pre-disaster
      health history of victims of man-made disasters in their practices.

PMID- 16595545
TI  - Growth cone steering by a physiological electric field requires dynamic
      microtubules, microfilaments and Rac-mediated filopodial asymmetry.
AB  - Electric fields (EFs) resembling those in the developing and regenerating nervous
      systems steer growth cones towards the cathode. Requirements for actin
      microfilaments, microtubules and their interactions during EF growth cone
      steering have been presumed, but remain unproven. Here, we demonstrate essential
      roles for dynamic microfilaments and microtubules in cathode-directed migration.
      Cathodal turning of growth cones on cultured Xenopus embryonic spinal neurons was
      attenuated significantly by nanomolar concentrations of the microfilament
      inhibitor latrunculin, the microtubule-stabilising drug taxol, or the microtubule
      destabilising drugs vinblastine or nocodazole. Dynamically, the cathodal bias of
      filopodia preceded cathodal turning of the growth cone, suggesting an instructive
      role in EF-induced steering. Lamellipodial asymmetry accompanied turning.
      Filopodia and lamellipodia are regulated by the GTPases Cdc42 and Rac,
      respectively, and, as shown in the companion paper in this issue, peptides that
      selectively prevented effector binding to the CRIB domains of Cdc42 or Rac
      abolished cathodal growth cone turning during 3 hours of EF exposure. Here, the
      Rac peptide suppressed lamellipodium formation, increased the number of
      filopodia, abolished cathodal filopodial orientation, and prevented cathodal
      steering. The Cdc42 peptide suppressed filopodium formation, increased
      lamellipodial area and prevented cathodal steering. The cathodal bias of
      lamellipodia was independent of Cdc42 CRIB activity and was not sufficient for
      cathodal steering in the absence of filopodia, but the cathodal bias of filopodia
      through Rac CRIB activity was necessary for cathodal turning. Understanding the
      mechanism for cathodal growth cone guidance will enhance the emerging clinical
      effort to stimulate human spinal cord regeneration through EF application.

PMID- 16595546
TI  - Temporally and spatially coordinated roles for Rho, Rac, Cdc42 and their
      effectors in growth cone guidance by a physiological electric field.
AB  - Although it is known that neuronal growth cones migrate towards the cathode of an
      applied direct current (DC) electric field (EF), resembling the EF present in the
      developing nervous system, the underlying mechanism remains unclear. Here, we
      demonstrate temporally and spatially coordinated roles for the GTPases Rac, Cdc42
      and Rho and their effectors. Growth cones of cultured Xenopus embryonic spinal
      neurons turned towards the cathode but collective inhibition of Rho, Rac and
      Cdc42 attenuated turning. Selective inhibition of Rho, Cdc42 or Rac signalling
      revealed temporally distinct roles in steering by an electrical gradient. Rho,
      Rac and Cdc42 are each essential for turning within the initial 2 hours (early
      phase). Later, Rho and Cdc42 signals remain important but Rac signalling
      dominates. The EF increased Rho immunofluorescence anodally. This correlated
      spatially with collapsed growth cone morphology and reduced anodal migration
      rates, which were restored by Rho inhibition. These data suggest that anodally
      increased Rho activity induces local cytoskeletal collapse, biasing growth cone
      advance cathodally. Collapse might be mediated by the Rho effectors p160 Rho
      kinase and myosin light chain kinase since their inhibition attenuated early
      turning. Inhibitors of phosphoinositide 3-kinase, MEK1/2 or p38 mitogen-activated
      protein kinase (MAPK) did not affect turning behaviour, eliminating them
      mechanistically. We propose a mechanism whereby Rac and Cdc42 activities dominate
      cathodally and Rho activity dominates anodally to steer growth cones towards the
      cathode. The interaction between Rho GTPases, the cytoskeleton and growth cone
      dynamics is explored in the companion paper published in this issue. Our results
      complement studies of growth cone guidance by diffusible chemical gradients and
      suggest that growth cones might interpret these co-existing guidance cues
      selectively.

PMID- 16595547
TI  - Ablation of connexin43 in uterine smooth muscle cells of the mouse causes delayed
      parturition.
AB  - Gap junctions are characteristically increased in the myometrium during term and
      preterm delivery and are thought to be essential for the development of uterine
      contractions during labour. Expression of connexin43 (Cx43), the major myometrial
      gap junction protein, is increased during delivery. We have generated a mouse
      mutant (Cx43fl/fl:SM-CreERT2), in which the coding region of Cx43 can be
      specifically deleted in smooth muscle cells at any given time point by
      application of tamoxifen. By this approach, we were able to study long-term
      effects on myometrial functions that are necessary for parturition as well as gap
      junction intercellular communication in primary myometrial cell cultures. We
      found a prolongation of the pregnancy in 82% of tamoxifen-treated Cx43fl/fl:SM
      CreERT2 mice as well as decreased dye coupling in cultured primary myocytes of
      these animals. Other parturition-specific parameters such as the regulation of
      oxytocin receptor, prostaglandin F receptor or progesterone remained unchanged.
      Our results indicate the important function of Cx43 during parturition in the
      living animal and suggest further strategies to investigate the role of connexins
      in uterine contractility in transgenic mice.

PMID- 16595548
TI  - Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a
      poly(ADP-ribosyl)ation-dependent mechanism.
AB  - Multiple functions have been reported for the transcription factor and candidate
      tumour suppressor, CTCF. Among others, they include regulation of cell growth,
      differentiation and apoptosis, enhancer-blocking activity and control of
      imprinted genes. CTCF is usually localized in the nucleus and its subcellular
      distribution during the cell cycle is dynamic; CTCF was found associated with
      mitotic chromosomes and the midbody, suggesting different roles for CTCF at
      different stages of the cell cycle. Here we report the nucleolar localization of
      CTCF in several experimental model systems. Translocation of CTCF from
      nucleoplasm to the nucleolus was observed after differentiation of K562 myeloid
      cells and induction of apoptosis in MCF7 breast cancer cells. CTCF was also found
      in the nucleoli in terminally differentiated rat trigeminal ganglion neurons.
      Thus our data show that nucleolar localization of CTCF is associated with growth
      arrest. Interestingly, the 180 kDa poly(ADP-ribosyl)ated isoform of CTCF was
      predominantly found in the nucleoli fractions. By transfecting different CTCF
      deletion constructs into cell lines of different origin we demonstrate that the
      central zinc-finger domain of CTCF is the region responsible for nucleolar
      targeting. Analysis of subnucleolar localization of CTCF revealed that it is
      distributed homogeneously in both dense fibrillar and granular components of the
      nucleolus, but is not associated with fibrillar centres. RNA polymerase I
      transcription and protein synthesis were required to sustain nucleolar
      localization of CTCF. Notably, the labelling of active transcription sites by in
      situ run-on assays demonstrated that CTCF inhibits nucleolar transcription
      through a poly(ADP-ribosyl)ation-dependent mechanism.

PMID- 16595549
TI  - Evidence for a role of transmembrane protein p25 in localization of protein
      tyrosine phosphatase TC48 to the ER.
AB  - T-cell protein tyrosine phosphatase gives rise to two splice isoforms: TC48,
      which is localized to the endoplasmic reticulum (ER) and TC45, a nuclear protein.
      The present study was undertaken to identify proteins that are involved in
      targeting TC48 to the ER. We identified two TC48-interacting proteins, p25 and
      p23, from a yeast two-hybrid screen. p23 and p25 are members of a family of
      putative cargo receptors that are important for vesicular trafficking between
      Golgi complex and ER. Both p23 and p25 associate with overexpressed TC48 in Cos-1
      cells as determined by coimmunoprecipitation. A significant amount of TC48
      colocalized initially with ERGIC and Golgi complex markers (in addition to ER and
      nuclear membrane localization) and was then retrieved to the ER. Coexpression
      with p25 enhanced ER localization of TC48, whereas coexpression with p23 resulted
      in its trapping in membranous structures. Coexpression of a p25 mutant lacking
      the ER-localization signal KKxx resulted in enhanced Golgi localization of TC48.
      Forty C-terminal amino acid residues of TC48 (position 376-415) were sufficient
      for interaction with p23 (but not with p25) and targeted green fluorescence
      protein (GFP) to the Golgi complex. Targeting of GFP to the ER required 66 C
      terminal amino acid residues of TC48 (position 350-415), which showed interaction
      with p25 and p23. We suggest that TC48 translocates to the Golgi complex along
      the secretory pathway, whereas its ER localization is maintained by selective
      retrieval enabled by interactions with p25 and p23.

PMID- 16595551
TI  - Relationship between human sperm-hyaluronan binding assay and fertilization rate
      in conventional in vitro fertilization.
AB  - BACKGROUND: Sperm-hyaluronan-binding assay (HBA) is one of the commercial kits
      being marketed for routine testing of sperm maturity and fertility. However,
      there is no report of whether the HBA can provide additional information over
      standard semen analysis for sperm-fertilizing ability. The objective of this
      study was to investigate the relationship between HBA and fertilization rate in
      conventional IVF. METHODS: A total of 175 IVF patients with > or = 3 mature
      oocytes inseminated were included in the study. Both the standard semen analysis
      and the HBA were performed on the same ejaculated sperm samples used for IVF
      treatments. Relationships between the semen analysis and the HBA results and
      fertilization rate were analysed by both the Spearman test and the multivariate
      logistic regression analysis. RESULTS: Both total and progressive sperm motility
      and normal morphology were highly correlated with HBA scores. While both normal
      sperm morphology and HBA scores were statistically significantly related to
      fertilization rates, the HBA was less significant than normal sperm morphology.
      The HBA does not provide additional information for identifying patients with a
      poor fertilization rate. CONCLUSION: HBA is highly significantly correlated with
      sperm motility and morphology but is less significant than sperm morphology in
      relation to the fertilization rate in IVF. Thus, the clinical predictive value of
      HBA for sperm-fertilizing ability in vitro is limited.

PMID- 16595550
TI  - Caldesmon is an integral component of podosomes in smooth muscle cells.
AB  - Podosomes are highly dynamic actin-based structures commonly found in motile and
      invasive cells such as macrophages, osteoclasts and vascular smooth muscle cells.
      Here, we have investigated the role of caldesmon, an actin-binding protein, in
      the formation of podosomes in aortic smooth muscle A7r5 cells induced by the
      phorbol ester PDBu. We found that endogenous low molecular weight caldesmon (l
      caldesmon), which was normally localised to actin-stress fibres and membrane
      ruffles, was recruited to the actin cores of PDBu-induced podosomes.
      Overexpression of l-caldesmon in A7r5 cells caused dissociation of actin-stress
      fibres and disruption of focal adhesion complexes, and significantly reduced the
      ability of PDBu to induce podosome formation. By contrast, siRNA interference of
      caldesmon expression enhanced PDBu-induced formation of podosomes. The N-terminal
      fragment of l-caldesmon, CaD40, which contains the myosin-binding site, did not
      label stress fibres and was not translocated to PDBu-induced podosomes. Cad39,
      the C-terminal fragment housing the binding sites for actin, tropomyosin and
      calmodulin, was localised to stress fibres and was translocated to podosomes
      induced by PDBu. The caldesmon mutant, CadCamAB, which does not interact with
      Ca2+/calmodulin, was not recruited to PDBu-induced podosomes. These results show
      that (1) l-caldesmon is an integral part of the actin-rich core of the podosome;
      (2) overexpression of l-caldesmon suppresses podosome formation, whereas siRNA
      knock-down of l-caldesmon facilitates its formation; and (3) the actin-binding
      and calmodulin-binding sites on l-caldesmon are essential for the translocation
      of l-caldesmon to the podosomes. In summary, this data suggests that caldesmon
      may play a role in the regulation of the dynamics of podosome assembly and that
      Ca2+/calmodulin may be part of a regulatory mechanism in podosome formation.

PMID- 16595552
TI  - Dominant inheritance of premature ovarian failure associated with mutant
      mitochondrial DNA polymerase gamma.
AB  - BACKGROUND: Premature ovarian failure (POF) results in menopause before the age
      of 40. Recently, mutations in the catalytic subunit of mitochondrial DNA
      polymerase gamma (POLG) were shown to segregate with POF in families with
      progressive external ophthalmoplegia (PEO) and multiple large-scale
      rearrangements of mitochondrial DNA (mtDNA). METHODS AND RESULTS: A patient,
      mother and maternal grandmother are described, all presenting with POF and PEO.
      The mother developed parkinsonism in her sixth decade. Normal mtDNA sequence
      excluded mitochondrial inheritance. Sequence analysis of polymerase gamma
      revealed a dominant Y955C mutation that segregated with disease. Southern blot
      analysis demonstrated mtDNA depletion in fibroblasts (43% of controls). In
      contrast, multiple rearrangements of mtDNA were seen in skeletal muscle,
      consistent with the relative sparing of nuclear-encoded complex II activity
      compared with other respiratory chain enzymes. Immunoblotting of native gels
      showed that DNA polymerase gamma stability was not affected, whereas a reverse
      transcriptase primer-extension assay suggested a trend towards reduced polymerase
      activity in fibroblasts. CONCLUSIONS: This study confirms that POLG mutations can
      segregate with POF and parkinsonism and demonstrates for the first time that the
      Y955C mutation can lead to mtDNA depletion. Future screening projects will
      determine the frequency with which POLG is involved in the aetiology of POF and
      its impact on reproductive counselling.

PMID- 16595554
TI  - Computational recognition of potassium channel sequences.
AB  - MOTIVATION: Potassium channels are mainly known for their role in regulating and
      maintaining the membrane potential. Since this is one of the key mechanisms of
      signal transduction, malfunction of these potassium channels leads to a wide
      variety of severe diseases. Thus potassium channels are priority targets of
      research for new drugs, despite the fact that this protein family is highly
      variable and closely related to other channels, which makes it very difficult to
      identify new types of potassium channel sequences. RESULTS: Here we present a new
      method for identifying potassium channel sequences (PSM, Property Signature
      Method), which-in contrast to the known methods for protein classification-is
      directly based on physicochemical properties of amino acids rather than on the
      amino acids themselves. A signature for the pore region including the selectivity
      filter has been created, representing the most common physicochemical properties
      of known potassium channels. This string enables genome-wide screening for
      sequences with similar features despite a very low degree of amino acid
      similarity within a protein family.

PMID- 16595553
TI  - Relationships among ecologically important dimensions of plant trait variation in
      seven neotropical forests.
AB  - BACKGROUND AND AIMS: When ecologically important plant traits are correlated they
      may be said to constitute an ecological 'strategy' dimension. Through identifying
      these dimensions and understanding their inter-relationships we gain insight into
      why particular trait combinations are favoured over others and into the
      implications of trait differences among species. Here we investigated
      relationships among several traits, and thus the strategy dimensions they
      represented, across 2134 woody species from seven Neotropical forests. METHODS:
      Six traits were studied: specific leaf area (SLA), the average size of leaves,
      seed and fruit, typical maximum plant height, and wood density (WD). Trait
      relationships were quantified across species at each individual forest as well as
      across the dataset as a whole. 'Phylogenetic' analyses were used to test for
      correlations among evolutionary trait-divergences and to ascertain whether
      interspecific relationships were biased by strong taxonomic patterning in the
      traits. KEY RESULTS: The interspecific and phylogenetic analyses yielded
      congruent results. Seed and fruit size were expected, and confirmed, to be
      tightly related. As expected, plant height was correlated with each of seed and
      fruit size, albeit weakly. Weak support was found for an expected positive
      relationship between leaf and fruit size. The prediction that SLA and WD would be
      negatively correlated was not supported. Otherwise the traits were predicted to
      be largely unrelated, being representatives of putatively independent strategy
      dimensions. This was indeed the case, although WD was consistently, negatively
      related to leaf size. CONCLUSIONS: The dimensions represented by SLA, seed/fruit
      size and leaf size were essentially independent and thus conveyed largely
      independent information about plant strategies. To a lesser extent the same was
      true for plant height and WD. Our tentative explanation for negative WD-leaf size
      relationships, now also known from other habitats, is that the traits are
      indirectly linked via plant hydraulics.

PMID- 16595555
TI  - ALTree: association detection and localization of susceptibility sites using
      haplotype phylogenetic trees.
AB  - Finding the genes involved in complex diseases susceptibility and among those
      genes, localizing the variant sites explaining this susceptibility is a major
      goal of genetic epidemiology. In this context, haplotypic methods that use the
      joint information on several markers may be of particular interest. When the
      number of haplotypes is large, a grouping may be required. Phylogenetic trees
      allow such groupings of haplotypes based on their evolutionary history and may
      help in the detection and localization of disease susceptibility sites. In this
      paper, we present a new software to perform phylogeny-based association and
      localization analysis.

PMID- 16595556
TI  - Integrating multi-attribute similarity networks for robust representation of the
      protein space.
AB  - MOTIVATION: A global view of the protein space is essential for functional and
      evolutionary analysis of proteins. In order to achieve this, a similarity network
      can be built using pairwise relationships among proteins. However, existing
      similarity networks employ a single similarity measure and therefore their
      utility depends highly on the quality of the selected measure. A more robust
      representation of the protein space can be realized if multiple sources of
      information are used. RESULTS: We propose a novel approach for analyzing multi
      attribute similarity networks by combining random walks on graphs with Bayesian
      theory. A multi-attribute network is created by combining sequence and structure
      based similarity measures. For each attribute of the similarity network, one can
      compute a measure of affinity from a given protein to every other protein in the
      network using random walks. This process makes use of the implicit clustering
      information of the similarity network, and we show that it is superior to naive,
      local ranking methods. We then combine the computed affinities using a Bayesian
      framework. In particular, when we train a Bayesian model for automated
      classification of a novel protein, we achieve high classification accuracy and
      outperform single attribute networks. In addition, we demonstrate the
      effectiveness of our technique by comparison with a competing kernel-based
      information integration approach.

PMID- 16595558
TI  - Effective similarity measures for expression profiles.
AB  - It is commonly accepted that genes with similar expression profiles are
      functionally related. However, there are many ways one can measure the similarity
      of expression profiles, and it is not clear a priori what is the most effective
      one. Moreover, so far no clear distinction has been made as for the type of the
      functional link between genes as suggested by microarray data. Similarly
      expressed genes can be part of the same complex as interacting partners; they can
      participate in the same pathway without interacting directly; they can perform
      similar functions; or they can simply have similar regulatory sequences. Here we
      conduct a study of the notion of functional link as implied from expression data.
      We analyze different similarity measures of gene expression profiles and assess
      their usefulness and robustness in detecting biological relationships by
      comparing the similarity scores with results obtained from databases of
      interacting proteins, promoter signals and cellular pathways, as well as through
      sequence comparisons. We also introduce variations on similarity measures that
      are based on statistical analysis and better discriminate genes which are
      functionally nearby and faraway. Our tools can be used to assess other similarity
      measures for expression profiles, and are accessible at
      biozon.org/tools/expression/

PMID- 16595557
TI  - NQ-Flipper: validation and correction of asparagine/glutamine amide rotamers in
      protein crystal structures.
AB  - The error rate of asparagine (Asn) and glutamine (Gln) amide rotamers in protein
      crystal structures is in the order of 20% and as a consequence the current
      Protein Database (PDB) contains approximately half a million incorrect Asn and
      Gln side-chain rotamers. Here we present NQ-Flipper, a web service based on
      knowledge-based potentials of mean force to automatically detect and correct
      erroneous rotamers. We achieve excellent agreement with expert curated data.

PMID- 16595559
TI  - HTS-Corrector: software for the statistical analysis and correction of
      experimental high-throughput screening data.
AB  - MOTIVATION: High-throughput screening (HTS) plays a central role in modern drug
      discovery, allowing for testing of >100,000 compounds per screen. The aim of our
      work was to develop and implement methods for minimizing the impact of systematic
      error in the analysis of HTS data. To the best of our knowledge, two new data
      correction methods included in HTS-Corrector are not available in any existing
      commercial software or freeware. RESULTS: This paper describes HTS-Corrector, a
      software application for the analysis of HTS data, detection and visualization of
      systematic error, and corresponding correction of HTS signals. Three new methods
      for the statistical analysis and correction of raw HTS data are included in HTS
      Corrector: background evaluation, well correction and hit-sigma distribution
      procedures intended to minimize the impact of systematic errors. We discuss the
      main features of HTS-Corrector and demonstrate the benefits of the algorithms.

PMID- 16595560
TI  - Pvclust: an R package for assessing the uncertainty in hierarchical clustering.
AB  - SUMMARY: Pvclust is an add-on package for a statistical software R to assess the
      uncertainty in hierarchical cluster analysis. Pvclust can be used easily for
      general statistical problems, such as DNA microarray analysis, to perform the
      bootstrap analysis of clustering, which has been popular in phylogenetic
      analysis. Pvclust calculates probability values (p-values) for each cluster using
      bootstrap resampling techniques. Two types of p-values are available:
      approximately unbiased (AU) p-value and bootstrap probability (BP) value.
      Multiscale bootstrap resampling is used for the calculation of AU p-value, which
      has superiority in bias over BP value calculated by the ordinary bootstrap
      resampling. In addition the computation time can be enormously decreased with
      parallel computing option.

PMID- 16595561
TI  - ProMAT: protein microarray analysis tool.
AB  - SUMMARY: ProMAT is a software tool for statistically analyzing data from enzyme
      linked immunosorbent assay microarray experiments. The software estimates
      standard curves, sample protein concentrations and their uncertainties for
      multiple assays. ProMAT generates a set of comprehensive figures for assessing
      results and diagnosing process quality. The tool is available for Windows or Mac,
      and is distributed as open-source Java and R code. AVAILABILITY: ProMAT is
      available at http://www.pnl.gov/statistics/ProMAT. ProMAT requires Java version
      1.5.0 and R version 1.9.1 (or more recent versions). ProMAT requires either
      Windows XP or Mac OS 10.4 or newer versions.

PMID- 16595562
TI  - Using mRNAs lengths to accurately predict the alternatively spliced gene products
      in Caenorhabditis elegans.
AB  - MOTIVATION: Computational gene prediction methods are an important component of
      whole genome analyses. While ab initio gene finders have demonstrated major
      improvements in accuracy, the most reliable methods are evidence-based gene
      predictors. These algorithms can rely on several different sources of evidence
      including predictions from multiple ab initio gene finders, matches to known
      proteins, sequence conservation and partial cDNAs to predict the final product.
      Despite the success of these algorithms, prediction of complete gene structures,
      especially for alternatively spliced products, remains a difficult task. RESULTS:
      LOCUS (Length Optimized Characterization of Unknown Spliceforms) is a new
      evidence-based gene finding algorithm which integrates a length-constraint into a
      dynamic programming-based framework for prediction of gene products. On a
      Caenorhabditis elegans test set of alternatively spliced internal exons, its
      performance exceeds that of current ab initio gene finders and in most cases can
      accurately predict the correct form of all the alternative products. As the
      length information used by the algorithm can be obtained in a high-throughput
      fashion, we propose that integration of such information into a gene-prediction
      pipeline is feasible and doing so may improve our ability to fully characterize
      the complete set of mRNAs for a genome. AVAILABILITY: LOCUS is available from
      http://ural.wustl.edu/software.html

PMID- 16595564
TI  - Life expectancy in patients with hereditary haemorrhagic telangiectasia.
AB  - BACKGROUND: There are few data on life expectancy in patients with hereditary
      haemorrhagic telangiectasia (HHT), a disorder with life-threatening
      complications. METHODS: Seventy HHT patients provided data on age and age at
      death of their HHT-affected parent, which was compared with that of the parent's
      non-affected partner. RESULTS: At the time of the study, 40 HHT parents (57.1%)
      vs. 36 (51.4%) non-HHT parents had died (p = 0.404). Median age at death was
      lower in HHT vs. non-HHT parents (63.2 vs. 70.0 years, respectively). The
      mortality of HHT parents showed an early peak in the under 50s and a late peak at
      60-79 years. HHT was the main risk factor influencing life expectancy after 30
      years (p < 0.05). No differences in survival probability were found in HHT
      patients with respect to sex (p = 0.37), or ENG vs. ALK-1 genotype (p < 0.9).
      DISCUSSION: Life expectancy appears to be significantly lower in HHT patients
      than in their partners. Prevention of HHT complications with screening programs
      could increase life expectancy.

PMID- 16595565
TI  - Evaluation of pramoxine ingestion as reported to poison centers.

PMID- 16595563
TI  - Presenting characteristics as predictors of duration of treatment in sarcoidosis.
AB  - BACKGROUND: Some sarcoidosis patients never need therapy, but many still require
      therapy more than 2 years after initial diagnosis. AIM: To determine what
      features at initial presentation are associated with treatment 2 years later.
      METHODS: Patients with biopsy-confirmed sarcoidosis enrolled in the ACCESS (A
      Case Control Etiologic Study of Sarcoidosis) study were initially evaluated
      within 6 months of diagnosis. Pulmonary function, chest X-ray and dyspnoea score
      were measured, and systemic therapy for the sarcoidosis recorded. Organ
      involvement was assessed using a standardized instrument. A subset (n = 215) were
      seen 18-24 months later for follow-up, and these patients constitute our study
      group. RESULTS: Ten patients had only received therapy before the first visit,
      with no further therapy, and were excluded from analysis. Of the remaining 205,
      95 were not on therapy at the initial visit and 75 (79%) of these were never
      treated during follow-up. Of the 110 initially on therapy, 52 (47%) remained on
      therapy at follow-up. Other initial features associated with continued therapy
      were the level of dyspnoea and predicted vital capacity. On logistic regression,
      only dyspnoea and therapy at initial visit remained significant. Patients on
      systemic therapy at initial evaluation were more likely to be on therapy at
      follow-up (OR 3.6, p = 0.003). Neither ethnicity nor gender independently
      predicted therapy at follow-up. DISCUSSION: This study group represents a sample
      of newly diagnosed sarcoidosis patients. However, this is a referral population,
      and there was no set protocol for treatment. Use of systemic therapy within the
      first 6 months after diagnosis appears to be strongly associated with continued
      use of therapy 2 years later.

PMID- 16595566
TI  - Atenolol-induced breast pain in a woman with hypertension.
AB  - OBJECTIVE: To describe a case of atenolol-induced breast pain and swelling in a
      patient receiving atenolol. CASE SUMMARY: A 54-year-old woman was diagnosed with
      hypertension with no existing comorbidity. The patient was not taking any
      prescription medications, but was using an herbal supplement and several other
      over-the-counter supplements. After diet and exercise failed to control the
      woman's blood pressure, atenolol 25 mg daily was initiated. She reported symptoms
      of insomnia 9 days after starting the medication. During a follow-up visit 5
      weeks later, the patient reported continued insomnia, as well as a 6 day history
      of breast pain, swelling, and tenderness. Atenolol was quickly titrated to
      discontinuation, and a thiazide diuretic was prescribed. Subsequently, the pain
      and swelling gradually resolved. DISCUSSION: Assessment using the Naranjo
      probability scale revealed that the adverse reaction was probably associated with
      atenolol. While rare cases of hyperprolactinemia and galactorrhea have been
      reported with beta-blocker use, no reports of breast pain caused by this drug
      class were identified in the literature. CONCLUSIONS: Atenolol has many reported
      adverse reactions, both common and rare; however, until this report, breast pain
      and swelling had not been documented adverse reactions. Clinicians should be
      aware that atenolol may be a cause of nonorganic breast pain and swelling in
      women.

PMID- 16595567
TI  - Screening tests for intended medication adherence among the elderly.
AB  - BACKGROUND: Medication nonadherence is increasingly recognized as a cause of
      preventable adverse events, hospitalizations, and poor healthcare outcomes. While
      comprehensive medication adherence assessment for the elderly is likely to
      identify and prevent drug-related problems, it is time consuming for patient and
      healthcare providers alike. OBJECTIVE: To identify screening tools to predict
      elderly patients' intended medication adherence that are suitable for primary
      care settings and community pharmacies. METHODS: This study evaluated 57 English
      speaking persons aged 65 years and older who were from diverse socioeconomic
      backgrounds. Intended adherence was quantified, and the relationships to
      demographic, medical history, socioeconomic, and literacy variables were
      determined. RESULTS: In a multivariate analysis with the composite MedTake Test
      (a quantitative measure of each subject's intent to adhere to prescribed oral
      medications) as the dependent variable, independent predictors of intended
      adherence included: age, car ownership in the last 10 years, receipt of food
      assistance in the last 10 years, number of over-the-counter (OTC) medicines, and
      REALM (Rapid Estimate of Adult Literacy in Medicine). The strongest predictor was
      the REALM word-recognition pronunciation test (beta = 0.666; R2 = 0.271; p <
      0.001). CONCLUSIONS: We observed that the REALM word-recognition pronunciation
      test, along with age, number of OTC drugs, and 2 socioeconomic questions,
      predicted the intent of seniors to correctly take their own prescribed oral
      medications.

PMID- 16595569
TI  - Discordance between availability of pharmacogenetics studies and pharmacogenetics
      based prescribing information for the top 200 drugs.
AB  - BACKGROUND: Despite growing numbers of pharmacogenetics studies, little
      pharmacogenetics-based prescribing information is available to practitioners. It
      is possible that the lack of prescribing data for commonly used drugs is due to a
      paucity of evidence-based pharmacogenetics literature for these agents.
      OBJECTIVE: To investigate the relationship between pharmacogenetics prescribing
      data in drug package inserts (PIs) and pharmacogenetics research literature for
      agents represented in the top 200 prescribed drugs for 2003. METHODS: A PubMed
      search (to August 7, 2004) was performed to identify pharmacogenetics studies
      relevant to the top 200 drugs. These data were compared with PIs for drugs in the
      top 200 list that contained pharmacogenetics prescribing information. RESULTS:
      Pharmacogenetics data in the literature were available for 71.3% of the top 200
      drugs. The gene involved coded for a drug-metabolizing enzyme in 34.5% of the
      literature sampled. The remaining 65.5% of the pharmacogenetics studies contained
      information largely related to genetic variability in target proteins and drug
      transporters. Three drugs with PIs containing pharmacogenetics prescribing
      information deemed to be useful to guide therapy were in the top 200 list
      (celecoxib, fluoxetine, pantoprazole). There was no consensus on the strength of
      association between genetic variability and drug response for these agents.
      CONCLUSIONS: The lack of specific pharmacogenetics-based prescribing information
      in PIs for commonly used drugs does not seem to be related to a paucity of
      pharmacogenetics data in the research literature. Rather, other factors
      including, but not limited to, the uncertain clinical relevance of genetic
      associations may make practical prescribing recommendations difficult.

PMID- 16595568
TI  - Cangrelor for treatment of coronary thrombosis.
AB  - OBJECTIVE: To review and assess available literature on the chemistry,
      pharmacology, pharmacodynamics, pharmacokinetics, clinical studies, adverse
      events, drug interactions, special populations, and dosing and administration for
      cangrelor, a product in late stage Phase II clinical trials. DATA SOURCES: A
      literature search of MEDLINE (1966-March 2006), International Pharmaceutical
      Abstracts (1970-February 2006), and Cochrane database (first quarter 2006) was
      conducted using key terms of cangrelor, AR-C69931MX, and P2Y12 receptor
      antagonist. Bibliographies of relevant articles were reviewed for additional
      references. The Medicines Company Web site was reviewed, and a company
      representative was contacted. STUDY SELECTION AND DATA EXTRACTION: Available
      English-language literature, including abstracts, preclinical studies, clinical
      trials, and review articles, was reviewed. DATA SYNTHESIS: Cangrelor is a P2Y12
      antagonist under development for treatment of acute coronary syndrome. Cangrelor
      has been studied as an intravenous infusion in doses of 2 or 4 microg/kg/min. It
      inhibits platelet aggregation with rapid onset and offset and does not require
      metabolism for therapeutic activity. Published Phase II trials have demonstrated
      safety and inhibition of platelet aggregation. CONCLUSIONS: Cangrelor is a
      promising investigational medication for inhibition of platelet aggregation in
      acute arterial coronary events. Phase II trials have shown safety and a greater
      inhibition of platelet aggregation over clopidogrel. Phase III trials will
      provide more definitive information on clinical efficacy and safety. Until then,
      the role of cangrelor is uncertain.

PMID- 16595570
TI  - Update on prevention of meningococcal disease: focus on tetravalent meningococcal
      conjugate vaccine.
AB  - OBJECTIVE: To review the immunogenicity, efficacy, safety, and new
      recommendations for routine use of the tetravalent meningococcal conjugate
      vaccine (MCV4). DATA SOURCES: A MEDLINE search (1966-June 2005) was conducted
      using the key words Neisseria meningitidis and meningococcal vaccines for
      clinical trials limited to human research published in the English language.
      STUDY SELECTION AND DATA EXTRACTION: Randomized, controlled, multicenter trials
      were reviewed and included to evaluate the safety and efficacy of MCV4.
      Additional open-label trials on the use of MCV4 in children less than 24 months
      of age are included since these studies may be used to support the approval of
      the vaccine for use in children. Literature on epidemiology and pathology of
      meningococcal meningitis and the Advisory Committee on Immunization Practices
      (ACIP) recommendations were also reviewed. DATA SYNTHESIS: MCV4 is approved for
      active immunization of adolescents and adults between the ages of 11 and 55 years
      for the prevention of disease caused by N. meningitidis serogroups A, C, Y, and W
      135. MCV4 has been shown to have comparable immunogenicity and a similar adverse
      reaction profile to the tetravalent meningococcal polysaccharide vaccine (MPSV4).
      It is expected that MCV4 will provide a longer duration of protection from
      meningococcal disease than MPSV4. CONCLUSIONS: Based on lished immunogenicity,
      efficacy, and safety data, as well as the recent recommendations by the ACIP for
      its routine use, MCV4 is the preferred meningococcal vaccine for persons between
      11 and 55 years of age and should be included on pharmacy formularies.

PMID- 16595571
TI  - Risk of clozapine-associated agranulocytosis and mandatory white blood cell
      monitoring.
AB  - OBJECTIVE: To provide information for physicians and patients on which to base a
      decision as to whether to stop mandatory blood testing. DATA SOURCES: Articles on
      drug-induced blood dyscrasias were identified by searches of MEDLINE (1966
      September 2005) and review of their bibliographies. Novartis was asked to provide
      additional data on clozapine, leukopenia, agranulocytosis, and suicidality. STUDY
      SELECTION AND DATA EXTRACTION: Data on the chance of clozapine-induced leukopenia
      and agranulocytosis were combined with data about possible fatality and compared
      with the risks associated with other medications and with life in general. DATA
      SYNTHESIS: The chance of clozapine-induced leukopenia or agranulocytosis
      decreases exponentially over time. In the US, the chance in the second 6 months
      of treatment is 0.70/1000 patient-years and, after the first year, 0.39/1000
      patient-years. The case fatality rate of clozapine-induced agranulocytosis is
      estimated as 4.2-16%, depending on whether a granulocyte colony-stimulating
      factor is used. Nevertheless, treatment with clozapine reduces overall mortality,
      probably because it reduces suicidality. CONCLUSIONS: After at least 6 months'
      treatment with clozapine, the mortality involved in stopping white blood cell
      monitoring is about the same as the mortality associated with other medications,
      such as mianserin or phenylbutazone, and with life in general (traffic or
      occupational accident). If the patient has been well informed and wishes to stop
      the monitoring, it is a medically justifiable option to do so and is preferable
      to stopping treatment with clozapine since this drug reduces overall mortality.

PMID- 16595572
TI  - Ranolazine: a new approach to management of patients with angina.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, and clinical efficacy of
      ranolazine for the treatment of chronic stable angina. DATA SOURCES: MEDLINE was
      searched (1966-February 2006) using the English-language key terms ranolazine and
      chronic stable angina. Additional studies were identified from the bibliographies
      of the reviewed literature. STUDY SELECTION AND DATA EXTRACTION: Studies
      evaluating ranolazine, alone or in combination with other agents, were
      incorporated in this review. DATA SYNTHESIS: Ranolazine is a metabolic modulator
      designed to improve cardiac energy availability and cardiac metabolism. It is
      believed to be a partial fatty acid oxidation inhibitor. Ranolazine has been
      shown to improve exercise duration and time to anginal attacks without
      significantly affecting heart rate or blood pressure. Adverse effects of
      ranolazine are reported to be dose related. The elimination half-life of
      ranolazine is estimated to be between 1.4 and 1.9 hours for the immediate-release
      and 7 hours for sustained-release preparations. CONCLUSIONS: Ranolazine has a
      unique mechanism of action that is different from that of conventional agents. It
      has been studied as monotherapy or in combination with other commonly prescribed
      agents. It appears that ranolazine has a promising safety data profile and does
      not affect hemodynamic parameters. At this point, although ranolazine should not
      be used in place of conventional therapy, it appears that ranolazine may be
      considered in the management of symptomatic patients when standard antianginal
      medications are not tolerated or are ineffective.

PMID- 16595573
TI  - Hepatic veno-occlusive disease associated with immunosuppressive cyclophosphamide
      dosing and roxithromycin.
AB  - OBJECTIVE: To report on a patient developing hepatic veno-occlusive disease while
      being treated with immunosuppressive doses of cyclophosphamide (< or =2 mg/kg).
      CASE SUMMARY: A 66-year-old woman with autoimmune hemolytic anemia developed
      hepatic veno-occlusive disease while being treated with immunosuppressive
      cyclophosphamide 100 mg/day in combination with roxithromycin (total dose 600
      mg/day). After all drugs were stopped, the patient recovered within 2 weeks. The
      Naranjo probability scale indicated a probable relationship between veno
      occlusive disease and treatment with cyclophosphamide in this patient.
      DISCUSSION: Since roxithromycin inhibits CYP3A4, which is involved with
      cyclophosphamide metabolism, a drug-drug interaction could have been responsible.
      In addition, roxithromycin is an inhibitor of the drug transporter P
      glycoprotein, possibly leading to accumulation of cyclophosphamide in endothelial
      cells. Alternatively, since cyclophosphamide has been reported to induce
      apoptosis, roxithromycin could have rendered endothelial cells more vulnerable
      for apoptosis. CONCLUSIONS: In specific patients, cyclophosphamide can be
      associated with hepatic veno-occlusive disease at immunosuppressive doses.

PMID- 16595574
TI  - Comment: analysis of severe adverse events related to the use of mifepristone as
      an abortifacient.

PMID- 16595575
TI  - Localization of S-nitrosoglutathione and expression of S-nitrosoglutathione
      reductase in pea plants under cadmium stress.
AB  - S-nitrosoglutathione (GSNO) is considered a natural nitric oxide (NO.) reservoir
      and a reactive nitrogen intermediate in animal cells, but little is known about
      this molecule and its metabolism in plant systems. In this work, using pea plants
      as a model system, the presence of GSNO in collenchyma cells was demonstrated by
      an immunohistochemical method. When pea plants were grown with a toxic Cd
      concentration (50 microM) the content of GSNO in collenchyma cells was
      drastically reduced. Determination of the nitric oxide (NO.) and gluthathione
      contents in leaves by confocal laser scanning microscopy and HPLC, respectively,
      showed a marked decrease of both compounds in plants treated with cadmium. The
      analysis of the S-nitrosoglutathione reductase (GSNOR) activity and its
      transcript expression in leaves showed a reduction of 31% by cadmium. These
      results indicate that GSNO is associated with a specific plant cell type, and
      this metabolite and its related catabolic activity, GSNOR, are both down
      regulated under Cd stress.

PMID- 16595576
TI  - Imaging the production of singlet oxygen in vivo using a new fluorescent sensor,
      Singlet Oxygen Sensor Green.
AB  - Singlet oxygen is known to be produced by cells in response to photo-oxidative
      stresses and wounding. Due to singlet oxygen being highly reactive, it is thought
      to have a very short half-life in biological systems and, consequently, it is
      difficult to detect. A new commercially available reagent (singlet oxygen sensor
      green, SOSG), which is highly selective for singlet oxygen, was applied to a
      range of biological systems that are known to generate singlet oxygen. Induction
      of singlet oxygen production by the addition of myoglobin to liposome
      preparations demonstrated that the singlet oxygen-induced increases in SOSG
      fluorescence closely followed the increase in the concentration of conjugated
      dienes, which is stoichiometrically related to singlet oxygen production.
      Applications of photo-oxidative stresses to diatom species and leaves, which are
      known to result in the production of singlet oxygen, produced large increases in
      SOSG fluorescence, as did the addition of 3-(3',4'-dichlorophenyl)1,1
      dimethylurea (DCMU) to these systems, which inhibits electron transport in
      photosystem II and stimulates singlet oxygen production. The conditional
      fluorescent (flu) mutant of Arabidopsis produces singlet oxygen when exposed to
      light after a dark period, and this coincided with a large increase in SOSG
      fluorescence. Wounding of leaves was followed by an increase in SOSG
      fluorescence, even in the dark. It is concluded that SOSG is a useful in vivo
      probe for the detection of singlet oxygen.

PMID- 16595577
TI  - Doing the unexpected: proteins involved in hydrogen peroxide perception.
AB  - A look back at the early literature on reactive oxygen species (ROS) gives the
      impression that these small inorganic molecules had a singular defined role, that
      of host defence in mammalian systems. However, it is now known that their roles
      also include a major part in cell signalling, in a broad range of organisms from
      mammals to plants. Similarly, a look back at papers on the proteins now thought
      to be involved in the perception of hydrogen peroxide (H(2)O(2)) will show that
      they too had defined functions assigned to them, completely independent to
      H(2)O(2) signalling. These proteins have disparate roles, in ethylene perception
      or even major metabolic pathways such as glycolysis. However, the chemistry of
      H(2)O(2) sensing dictates that the proteins have a commonality, with active thiol
      groups being potential ROS targets. The challenge now is to determine the full
      range of proteins which may partake in the role of H(2)O(2) perception, and to
      determine the mechanisms by which the signal is transmitted to the next players
      in the signal transduction pathways.

PMID- 16595578
TI  - A versatile method for deciphering plant membrane proteomes.
AB  - Proteomics is a very powerful approach to link the information contained in
      sequenced genomes, like that of Arabidopsis, to the functional knowledge provided
      by studies of plant cell compartments. This article summarizes the different
      steps of a versatile strategy that has been developed to decipher plant membrane
      proteomes. Initiated with envelope membranes from spinach chloroplasts, this
      strategy has been adapted to thylakoids, and further extended to a series of
      membranes from the model plant Arabidopsis: chloroplast envelope membranes,
      plasma membrane, and mitochondrial membranes. The first step is the preparation
      of highly purified membrane fractions from plant tissues. The second step in the
      strategy is the fractionation of membrane proteins on the basis of their physico
      chemical properties. Chloroform/methanol extraction and washing of membranes with
      NaOH, NaCl or any other agent led to the simplification of the protein content of
      the fraction to be analysed. The next step is the genuine proteomic step, i.e.
      the separation of proteins by 1D-gel electrophoresis followed by in-gel
      proteolytic digestion of the polypeptides, analysis of the proteolytic peptides
      using mass spectrometry, and protein identification by searching through
      databases. The last step is the validation of the procedure by checking the
      subcellular location. The results obtained by using this strategy demonstrate
      that a combination of different proteomics approaches, together with
      bioinformatics, indeed provide a better understanding of the biochemical
      machinery of the different plant membranes at the molecular level.

PMID- 16595579
TI  - Proteome of amyloplasts isolated from developing wheat endosperm presents
      evidence of broad metabolic capability.
AB  - By contrast to chloroplasts, our knowledge of amyloplasts--organelles that
      synthesize and store starch in heterotrophic plant tissues--is in a formative
      stage. While our understanding of what is considered their primary function, i.e.
      the biosynthesis and degradation of starch, has increased dramatically in recent
      years, relatively little is known about other biochemical processes taking place
      in these organelles. To help fill this gap, a proteomic analysis of amyloplasts
      isolated from the starchy endosperm of wheat seeds (10 d post-anthesis) has been
      conducted. The study has led to the identification of 289 proteins that function
      in a range of processes, including carbohydrate metabolism, cytoskeleton/plastid
      division, energetics, nitrogen and sulphur metabolism, nucleic acid-related
      reactions, synthesis of various building blocks, protein-related reactions,
      transport, signalling, stress, and a variety of other activities grouped under
      'miscellaneous'. The function of 12% of the proteins was unknown. The results
      highlight the role of the amyloplast as a starch-storing organelle that fulfills
      a spectrum of biosynthetic needs of the parent tissue. When compared with a
      recent proteomic analysis of whole endosperm, the current study demonstrates the
      advantage of using isolated organelles in proteomic studies.

PMID- 16595580
TI  - The suffulta mutation in tomato reveals a novel method of plastid replication
      during fruit ripening.
AB  - Mutant alleles at the suffulta locus of tomato dramatically affect the pattern of
      plastid division throughout the plant, resulting in few, greatly enlarged
      chloroplasts in leaf and stem cells. suffulta plants are compromised in growth
      and have distinctly pale stems. The green developing tomato fruit are generally
      paler compared with the wild type, but ripe red fruit are much more similar in
      colour and pigment content. By using plastid-targeted green fluorescent protein,
      the underlying plastid phenotypes in the ripening suffulta fruit reveal that
      enlarged chlorophyll-containing chloroplasts degenerate and give rise to a wild
      type-like population of chromoplasts in ripe fruit by a process of plastid
      budding and fragmentation, resulting in a heterogeneous population of plastid
      derived structures which eventually become chromoplasts. In stomatal guard cells,
      plastid-derived structures lacking chlorophyll, but containing GFP, are also
      observed, especially in guard cells which completely lack normal chloroplasts.
      How this novel 'replication' process in suffulta relates to conventional plastid
      division and stromule formation is discussed.

PMID- 16595581
TI  - Arabidopsis and tobacco plants ectopically expressing the soybean antiquitin-like
      ALDH7 gene display enhanced tolerance to drought, salinity, and oxidative stress.
AB  - Despite extensive studies in eukaryotic aldehyde dehydrogenases, functional
      information about the ALDH7 antiquitin-like proteins is lacking. A soybean
      antiquitin homologue gene, designated GmTP55, has been isolated which encodes a
      dehydrogenase motif-containing 55 kDa protein induced by dehydration and salt
      stress. GmTP55 is closely related to the stress-induced plant antiquitin-like
      proteins that belong to the ALDH7 family. Transgenic tobacco (Nicotiana tabacum)
      and Arabidopsis (Arabidopsis thaliana) plants constitutively expressing GmTP55
      have been obtained in order to examine the physiological role of this enzyme
      under a variety of stress conditions. Ectopic expression of GmTP55 in both
      Arabidopsis and tobacco conferred tolerance to salinity during germination and to
      water deficit during plant growth. Under salt stress, the germination efficiency
      of both transgenic tobacco and Arabidopsis seeds was significantly higher than
      that of their control counterparts. Likewise, under progressive drought, the
      transgenic tobacco lines apparently kept the shoot turgidity to a normal level,
      which contrasted with the leaf wilt phenotype of control plants. The transgenic
      plants also exhibited an enhanced tolerance to H(2)O(2)- and paraquat-induced
      oxidative stress. Both GmTP55-expressing Arabidopsis and tobacco seeds germinated
      efficiently in medium supplemented with H(2)O(2), whereas the germination of
      control seeds was drastically impaired. Similarly, transgenic tobacco leaf discs
      treated with paraquat displayed a significant reduction in the necrotic lesions
      as compared with control leaves. These transgenic lines also exhibited a lower
      concentration of lipid peroxidation-derived reactive aldehydes under oxidative
      stress. These results suggest that antiquitin may be involved in adaptive
      responses mediated by a physiologically relevant detoxification pathway in
      plants.

PMID- 16595582
TI  - Oxalate accumulation and regulation is independent of glycolate oxidase in rice
      leaves.
AB  - Cellular oxalate, widely distributed in many plants, is implicated to play
      important roles in various functions and is also known to affect food qualities
      adversely in fruits and vegetables. How oxalate is regulated in plants is
      currently not well understood. Glycolate oxidase (GLO) has long been considered
      as an important player in oxalate accumulation in plants. To gain further insight
      into the biochemical and molecular mechanisms, the possible roles of GLO in the
      process were studied. Drastically different levels of oxalate could be achieved
      by treating rice with various nitrogen forms (nitrate versus ammonium). While
      nitrate stimulated oxalate accumulation, ammonium reduced its level. Such
      treatments resulted in similar pattern changes for some other related organic
      acids, such as glycolate, oxaloacetate, and malate. By feeding plants with
      exogenous glycolate it was possible almost completely to restore the ammonium
      decreased oxalate level. Under the two treatments few differences were observed
      for GLO mRNA levels, protein levels, and in vitro activities. Both K(m) for
      glycolate/glyoxylate and K(i) for oxalate remained almost the same for GLO
      purified from either nitrate- or ammonium-fed leaves. A further in vivo study,
      with transgenic plants carrying an estradiol-inducible GLO antisense gene, showed
      that, while the estradiol-induced antisense expression remarkably reduced both
      GLO protein levels and activities, oxalate levels were not significantly altered
      in the estradiol-treated transgenic plants. Taken together, it is suggested that
      oxalate accumulation and regulation is independent of GLO in rice leaves.

PMID- 16595583
TI  - Evolution of bone and plasma concentration of lanthanum in dialysis patients
      before, during 1 year of treatment with lanthanum carbonate and after 2 years of
      follow-up.
AB  - BACKGROUND: Lanthanum carbonate (LC) has been proposed as a new phosphate binder.
      Presented here are the results from one centre that participated in a multicentre
      trial to assess the effect of treatment with LC and calcium carbonate (CC) on the
      evolution of renal osteodystrophy in dialysis patients. Bone biopsies were
      performed at baseline, after 1 year of treatment and after a further 2-year
      follow-up period to assess the lanthanum concentration in bone and plasma.
      METHODS: Twenty new dialysis patients were randomized to receive LC (median dose
      1250 mg) for 1 year (n = 10), followed by 2 years of CC treatment or CC (n = 10)
      during the whole study period (3 years). RESULTS: After 36 weeks of treatment,
      steady state was reached with plasma lanthanum levels varying around 0.6 ng/ml.
      Six weeks after cessation of 1 year of treatment, the plasma lanthanum levels
      declined to a value of 0.17 +/- 0.12 ng/ml (P < 0.05) and after 2 years to 0.09
      +/- 0.03 ng/ml. Plasma and bone lanthanum levels did not correlate with the
      average lanthanum dose at any time point. The mean bone concentration in patients
      receiving LC increased from 0.05 +/- 0.03 to 2.3 +/- 1.6 microg/g (P < 0.05)
      after 1 year and slightly decreased at the end of the study to 1.9 +/- 1.6
      microg/g (P < 0.05). CONCLUSIONS: Bone deposition after 1 year of treatment with
      LC is low (highest concentration: 5.5 microg/g). There is a slow release of
      lanthanum from its bone deposits 2 years after the discontinuation of the
      treatment and no association with aluminium-like bone toxicity.

PMID- 16595584
TI  - Geographic, ethnic, age-related and temporal variation in the incidence of end
      stage renal disease in Europe, Canada and the Asia-Pacific region, 1998-2002.
AB  - BACKGROUND: Only unbiased estimates of end-stage renal disease (ESRD) incidence
      and trends are useful for disease control-identification of risk factors and
      measuring the effect of intervention. METHODS: Age- and sex-standardized
      incidences (with trends) were calculated for all-cause and diabetic/non-diabetic
      ESRD for persons aged 0-14, 15-29, 30-44 and 45-64 years in 13 populations
      identified geographically, and six populations identified by ethnicity. RESULTS:
      The incidence of ESRD varied most with age, ethnicity and prevalence of diabetes.
      All non-Europid populations had excess ESRD, chiefly due to rates of type 2
      diabetic ESRD that were greater than accounted for by community prevalences of
      diabetes. Their rates of non-diabetic ESRD also were raised, with contributions
      from most common primary renal diseases except type 1 diabetic nephropathy and
      polycystic kidney disease. The ESRD rates generally were low, and more similar
      than different, in Europid populations, except for variable contributions from
      type 1 (high in Finland, Sweden, Denmark and Canada) and type 2 (high in Austria
      and Canada) diabetes. In Europid populations during 1998-2002, all-cause ESRD
      declined by 2% per year in persons aged 0-44 years, and all non-diabetic ESRD by
      a similar amount in persons aged 45-64 years, in whom diabetic ESRD had increased
      by 3% per year. CONCLUSIONS: Increased susceptibility to type 2 diabetes and to
      kidney disease progression characterizes excess ESRD in non-Europid peoples. The
      decline in all-cause ESRD in young persons, and non-diabetic ESRD in the middle
      aged, probably reflects improving management of progressive renal disease.

PMID- 16595585
TI  - Hydrochlorothiazide in CLDN16 mutation.
AB  - BACKGROUND: Hydrochlorothiazide (HCT) is applied in the therapy of familial
      hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) caused by
      claudin-16 (CLDN16) mutation. However, the short-term efficacy of HCT to reduce
      hypercalciuria in FHHNC has not yet been demonstrated in a clinical trial.
      METHODS: Four male and four female patients with FHHNC and CLDN16 mutation, under
      long-standing HCT therapy (0.4-1.2 mg/kg, median 0.9 mg/kg, dose according to
      calciuria), aged 0.7-22.4 years, were included in a clinical study to investigate
      the effect of HCT on calciuria. The study design consisted of three periods:
      continued therapy for 4 weeks, HCT withdrawal for 6 weeks and restart of therapy
      at the same dose for 4 weeks. Calciuria and magnesiuria were assessed weekly as
      Ca/creat and Mg/creat ratio, every 2 weeks in 24 h urine, and serum Mg, K and
      kaliuria (s-Mg, s-K and K/creat) at weeks 0, 6, 10 and 14. The data of each study
      period were averaged and analysed by Friedman and Wilcoxon test. RESULTS:
      Ca/creat was significantly reduced by HCT (median before/at/after withdrawal
      0.76/1.24/0.77 mol/mol creat; n = 8, P<0.05). The reduction of Ca/24 h by HCT was
      not statistically significant (0.13/0.19/0.13 mmol/kg x 24 h; n = 5). Serum Mg
      (0.51/0.64/0.56 mmol/l; n = 8, P<0.05) and Serum K (3.65/4.35/3.65 mmol/l; n = 8,
      P<0.05) were significantly higher during withdrawal. However, Mg/creat
      (0.98/0.90/0.90 mol/mol creat; n = 8), Mg/24 h (0.14/0.12/0.18 mmol/kg x 24h; n =
      5) and K/creat (6.3/8.4/6.2 mol/mol creat; n = 8) remained statistically
      unchanged during withdrawal. CONCLUSIONS: We demonstrated that HCT is effective
      in reducing hypercalciuria due to CLDN16 mutation on a short-term basis. However,
      the efficacy of HCT to attenuate disease progression remains to be elucidated.

PMID- 16595586
TI  - Post-transplantation anaemia in adult and paediatric renal allograft recipients
      Guy's Hospital experience.
AB  - BACKGROUND: The commonest cause of renal transplant loss is death with a
      functioning graft, usually from an excess of cardiovascular disease (CVD).
      Anaemia is becoming increasingly recognized as a reversible risk factor for the
      development of CVD. The purpose of this study was to estimate the prevalence of
      post-transplantation anaemia (PTA) in a large population of stable adult and
      paediatric renal transplants in one centre and to correlate the estimated
      glomerular filtration rate (eGFR), iron indices and the use of immunosuppressants
      with the prevalence of anaemia. METHODS: Every adult and paediatric patient with
      a functioning renal transplant and more than 3 months post-engraftment at Guy's
      hospital, London, as of 31 December 2004 and who had a valid creatinine and
      haemoglobin, in the period 1 September-31 December 2004 inclusive, was
      identified. A large database of clinical and biochemical indices was built up on
      the basis of medical notes and electronic patient records. Results were analysed
      for the prevalence of anaemia and risk factors for its development. Anaemia was
      defined according to the WHO criteria. All patients on treatment with an
      erythropoiesis stimulating agent were classified as anaemic, irrespective of
      haemoglobin. RESULTS: A total of 878 adults and 73 children were identified. Mean
      haemoglobin in adults was 12.9 +/- 1.6 g/dl and 11.8 +/- 1.4 g/dl in the
      children. Mean eGFR was 49.3 +/- 20.1 ml/min in adults and 65.7 +/- 18.8 ml/min
      in the paediatric cohort. Haemoglobin correlated positively with the eGFR in both
      cohorts (R = 0.33 and 0.29 in adults and children, respectively (P < 0.0001 for
      both)). We identified anaemia in 45.3% of adults and 22% in children. Ferritin
      levels were lower in children than in adults (79 +/- 93 vs 204 +/- 353 mg/l), but
      were higher in both cohorts among the non-anaemic populations than in those with
      anaemia. 58% of adults taking mycophenolate mofetil (MMF) were anaemic compared
      with 22% of children. One child, and 68 adults, were on recombinant
      erythropoietin. Multiple regression analyses identified age, female gender, eGFR
      and serum ferritin levels as independent predictors of haemoglobin in adult
      subjects. CONCLUSIONS: The prevalence of PTA was high in both adult and
      paediatric cohorts while comparatively few patients were being treated with
      erythropoiesis stimulating agents. The strongest predictors of haemoglobin in
      this cohort of patients were age, female sex and graft function.
      Immunosuppression including MMF or sirolimus was associated with a higher
      prevalence of anaemia, but this was likely to be the result of poorer graft
      function in these subjects. Iron deficiency did not seem to be a causative factor
      for anaemia in this population.

PMID- 16595587
TI  - Factors increasing the risk for stone formation in adult patients with cystic
      fibrosis.
AB  - BACKGROUND: Patients with cystic fibrosis (CF) are at high risk of
      nephrolithiasis (NL), but controversy still exists in terms of causes, including
      low urine output, hypercalciuria, hyperoxaluria, hyperuricosuria and
      hypocitraturia. Moreover, heterozygotes (H-CF), which may exhibit altered renal
      concentrating and diluting ability, have never studied so far. We, therefore,
      evaluated the metabolic and physicochemical data of adult CF and H-CF patients,
      comparing them to controls (C). METHODS: Twenty-nine CF patients (16 females,
      aged 28.4 +/- 7.1 years), 20 H-CF (12 females, aged 58.6 +/- 6.3 years) and 30 C
      (19 females, aged 39.1 +/- 11.5 years) underwent kidney ultrasound and metabolic
      evaluation to assess stone risk profile. RESULTS: There was a 21% prevalence of
      NL in CF vs 15% in H-CF. The CF group had elevated uric acid, but no other
      serological differences compared with the H-CF and C group. Conversely, the
      citrate and oxalate content in the urine differed significantly, being lower and
      higher, respectively. These changes held after correction for urine creatinine.
      Consequently, urine specimens were more supersaturated with calcium oxalate,
      despite exhibiting no differences for other relevant constituents. Uric acid
      increased only after normalization for the body weight and urine creatinine.
      Lower urine volume and more acidic pH produced mild supersaturation with uric
      acid in samples from CF, while urine from both H-CF and C remained
      undersaturated. H-CF had only minor increases in both urine oxalate and calcium
      oxalate supersaturation. CONCLUSIONS: This study confirms a high prevalence of
      kidney stones among CF patients associated with supersaturated urine. Their
      longer survival justifies diets and/or medications aimed at reducing the risk of
      forming stones.

PMID- 16595588
TI  - Genotoxicity and endoreduplication inducing activity of the food flavouring
      eugenol.
AB  - Eugenol (1-allyl-3-methoxy-4-hydroxybenzene; CAS No. 97-53-0), a compound
      extracted from clove oil and marjoram, is widely used as a food flavouring
      substance and is present in spices such as basil, cinnamon and nutmeg. It is also
      used in dentistry as an antiseptic and analgesic. Structural similarities with
      the class IIB IARC carcinogen safrole raises questions on its putative
      carcinogenicity. We evaluated the genotoxicity of eugenol in V79 cells using
      chromosomal aberrations (CAs), with and without rat liver biotransformation (S9).
      Eugenol induced CAs, with significant increases (3.5% aberrant cells) at 2500
      microM, demonstrating cytotoxicity at higher doses. S9 increased the induction of
      CAs in a dose-dependent manner to 15% at 2500 microM, with a high frequency of
      chromatid exchanges. In particular, an increase of endoreduplicated cells was
      observed, from 0% at control levels to 2.3 and 5% at 2000 microM, without and
      with S9, respectively. Since endoreduplication has been linked to inhibition of
      topoisomerase II, the topoisomerase II inhibitor ICRF-193 was used as a control
      inducer of endoreduplication (0.1-0.5 microM), increasing the number of
      endoreduplicated cells from 0% (control) to 3.5% (0.5 microM). S9 did not
      influence endoreduplication by ICRF-193. Both eugenol and ICRF-193 were also
      assayed for inhibition of topoisomerase II, and both showed a dose-dependent
      inhibitory effect, with ICRF-193 being a more potent inhibitor. Our results
      confirm that eugenol is genotoxic and raises the possibility of it having
      topoisomerase II inhibiting activity.

PMID- 16595590
TI  - Socioeconomic inequalities in very preterm birth rates.
AB  - AIMS: To investigate the extent of socioeconomic inequalities in the incidence of
      very preterm birth over the past decade. METHODS: Ecological study of all 549 618
      births in the former Trent health region, UK, from 1 January 1994 to 31 December
      2003. All singleton births of 22(+0) to 32(+6) weeks gestation (7 185 births)
      were identified from population surveys of neonatal services and stillbirths.
      Poisson regression was used to calculate incidence of very preterm birth (22-32
      weeks) and extremely preterm birth (22-28 weeks) by year of birth and decile of
      deprivation (child poverty section of the Index of Multiple Deprivation).
      RESULTS: Incidence of very preterm singleton birth rose from 11.9 per 1000 births
      in 1994 to 13.7 per 1000 births in 2003. Those from the most deprived decile were
      at nearly twice the risk of very preterm birth compared with those from the least
      deprived decile, with 16.4 per 1000 births in the most deprived decile compared
      with 8.5 per 1000 births in the least deprived decile (incidence rate ratio 1.94;
      95% CI (1.73 to 2.17)). This deprivation gap remained unchanged throughout the 10
      year period. The magnitude of socio-economic inequalities was the same for
      extremely preterm births (22-28 weeks incidence rate ratio 1.94; 95% CI (1.62 to
      2.32)). CONCLUSIONS: This large, unique dataset of very preterm births shows wide
      socio-economic inequalities that persist over time. These findings are likely to
      have consequences on the burden of long-term morbidity. Our research can assist
      future healthcare planning, the monitoring of socio-economic inequalities and the
      targeting of interventions in order to reduce this persistent deprivation gap.

PMID- 16595589
TI  - Perinatal and infant autopsy.
AB  - OBJECTIVES: To measure perinatal and infant autopsy rate in Wales over a 10-year
      period and study factors influencing the decision to perform an autopsy. DESIGN:
      Retrospective cohort analysis of data from the All Wales Perinatal Survey.
      METHODS: Autopsy rates were calculated over a 10-year period (1994-2003), and
      reasons for not performing an autopsy were noted. Two time periods, 1994-1996 and
      2001-2003 were compared, to study changing autopsy patterns. RESULTS: Over the 10
      year period, there were 4393 perinatal and infant deaths, with data available for
      4306 (98%) cases. Consent for autopsy was requested in 89% of cases and granted
      in 68%. When compared, the 3-year cumulative autopsy rate fell from 67.5% (95%
      confidence interval (CI) 65% to 69%) in 1994-1996, to 52.7% (CI 49% to 55%) in
      2001-2003. The difference in the proportion of autopsies performed between the
      two time periods was 14.8% (CI 11% to 18%). Parental consent was granted in 76.2%
      (CI 73% to 78%) of cases in 1994-1996 and 60% (CI 57% to 63%) of cases in 2001
      2003. The difference in proportion in consent for autopsy in the two time periods
      was 16% (CI 12% to 20%). CONCLUSIONS: A decrease in perinatal and infant autopsy
      rates has been found in Wales over the past 10 years. Parental refusal has been
      the main cause of this decline.

PMID- 16595591
TI  - Plasma angiotensin II concentrations in the early neonatal period.
AB  - BACKGROUND: There have been only a few reports on the renin-angiotensin system in
      low birthweight infants; in particular, plasma angiotensin II concentrations have
      not been studied. AIM: To investigate plasma angiotensin II concentrations in
      early neonatal infants including low birthweight infants. METHODS: Forty six
      patients were studied, of whom 14 weighed not less than 2500 g (normal birth
      weight), 16 weighed less than 2500 g but not less than 1500 g (moderately low
      birth weight), and 16 weighed less than 1500 g (very low birth weight). Blood
      samples were collected twice, on day 0 and day 7. Angiotensin II concentration
      was assayed using an enzyme immunoassay kit with a microplate. RESULTS: Geometric
      means of angiotensin II concentrations on day 7 were 19 pg/ml in the normal
      birthweight group, 28 pg/ml in the moderately low birthweight group, and 76 pg/ml
      in the very low birthweight group. The concentrations on day 7 in the very low
      birthweight group were significantly higher than those in the normal birthweight
      and moderately low birthweight groups (p = 0.005, p = 0.031). There were
      significant correlations between angiotensin II concentration on day 7 and
      gestational age (r(s) = -0.4, p = 0.007) and birth weight (r(s) = -0.36, p =
      0.016). CONCLUSIONS: Specific physiological conditions associated with a very low
      birth weight are thought to be responsible for the increased concentration of
      angiotensin II on day 7. It is necessary to measure angiotensin II concentration
      for a longer period after birth and study the factors that could influence it.

PMID- 16595592
TI  - RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes:
      follicular cells of Hashimoto's thyroiditis share low-level recombination events
      with a subset of papillary carcinoma.
AB  - CONTEXT: RET/papillary thyroid cancer (PTC) is a marker for papillary thyroid
      carcinoma, but its specificity has been questioned because of the disputed
      identification of RET/PTC in Hashimoto's thyroiditis (HT), oncocytic tumors, and
      other thyroid lesions. OBJECTIVE: The objective of this study was to determine 1)
      whether RET/PTC occurs in nonneoplastic follicular cells of HT, and 2) its
      recombination rate in thyroid tumors. DESIGN/PATIENTS: Forty-three samples from
      31 cases of HT were examined using interphase fluorescence in situ hybridization
      (FISH) with RET probes spanning the breakpoint region; real-time RT-PCR to
      quantify RET/PTC1, RET/PTC3, and c-RET transcripts; and RT-PCR after laser
      capture microdissection to enrich samples for follicular cells. The results were
      compared with those similarly obtained in 34 papillary carcinomas, eight thyroid
      oncocytic tumors, and 21 normal thyroids. RESULTS: Normal samples showed no RET
      rearrangement. Sixty-eight percent (15 of 22) of HT were positive by FISH; in all
      thyroiditis, signals were localized to rare nonneoplastic follicular cells; low
      level RET/PTC was identified in 17% (five of 29) of thyroiditis cases by real
      time RT-PCR and in an additional six of 11 real-time negative cases after
      increasing sensitivity with laser capture microdissection. Low RET/PTC1 levels
      were detected in 26% (nine of 34) of papillary carcinomas with an expression
      pattern and proportion of FISH-positive cells similar to those of the
      thyroiditis. Forty-seven percent (16 of 34) of papillary carcinomas and one
      oncocytic carcinoma expressed high RET/PTC1 mRNA levels. CONCLUSIONS: Low-level
      RET/PTC recombination occurs in nonneoplastic follicular cells in HT and in a
      subset of papillary thyroid carcinomas. RET/PTC expression variability should be
      taken into account for the molecular diagnosis of thyroid lesions. Overlapping
      molecular mechanisms may govern early stages of tumor development and
      inflammation in the thyroid.

PMID- 16595593
TI  - Free fatty acids are independently associated with all-cause and cardiovascular
      mortality in subjects with coronary artery disease.
AB  - CONTEXT: Free fatty acids (FFAs) are associated with several cardiovascular risk
      factors and exert harmful effects on the myocardium. OBJECTIVE: The aim of our
      study was to elucidate the relationship between FFAs and mortality in subjects
      who underwent coronary angiography. DESIGN, SETTING, AND PARTICIPANTS:
      Ludwigshafen Risk and Cardiovascular Health is a prospective cohort study of
      Caucasians who had undergone coronary angiography at baseline (1997-2000). During
      a median time of follow-up of 5.38 yr, 513 deaths had occurred among 3315 study
      participants with measured FFAs. MAIN OUTCOME MEASURE: Hazard ratios for
      mortality according to FFA levels were measured. RESULTS: At the fourth quartile
      of FFAs, fully adjusted hazard ratios for death from any cause and cardiovascular
      causes were 1.58 (P = 0.002) and 1.83 (P = 0.001), respectively. In persons with
      angiographic coronary artery disease (CAD), stable CAD, and unstable CAD, the
      predictive value of FFAs was similar to that in the entire cohort, but the
      association did not attain statistical significance in persons without CAD
      analyzed separately. FFA levels were not related to the presence of angiographic
      CAD but were elevated in subjects with unstable CAD, compared with probands with
      stable CAD. Furthermore, FFAs increased with the severity of heart failure and
      were positively correlated with N-terminal pro-B-type natriuretic peptide (P <
      0.001). CONCLUSIONS: FFA levels independently predict all-cause and
      cardiovascular mortality in subjects with angiographic CAD. A possible diagnostic
      use of FFAs warrants further studies, but our results may underline the
      importance of therapeutic approaches to influence FFA metabolism.

PMID- 16595594
TI  - Glycosylphosphatidylinositol-specific phospholipase d in nonalcoholic Fatty liver
      disease: a preliminary study.
AB  - CONTEXT: Recent studies demonstrated that de novo lipogenesis is increased in
      patients with nonalcoholic fatty liver disease (NAFLD). Patients with NAFLD also
      have plasma lipid abnormalities. These lipid abnormalities may in part be related
      to insulin resistance, which is common in patients with NAFLD. Insulin resistance
      is associated with alterations in proteins involved in lipid metabolism including
      glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), which is
      involved in triglyceride metabolism. OBJECTIVE: The objective of the study was to
      determine whether alterations in serum and hepatic levels of GPI-PLD occur in
      patients with NAFLD. DESIGN AND PATIENTS: We examined the following: 1) levels of
      serum GPI-PLD in nondiabetics with nonalcoholic steatohepatitis, compared with
      matched controls; 2) hepatic expression of GPI-PLD mRNA in patients with normal
      liver or NAFLD; and 3) effect of overexpressing GPI-PLD vs. beta-galactosidase
      (control) on global gene expression in a human hepatoma cell line. RESULTS: The
      serum levels of GPI-PLD were significantly higher in patients with nonalcoholic
      steatohepatitis than in matched controls (119 +/- 24 vs.105 +/- 15 microg/ml, P =
      0.047). The hepatic expression of GPI-PLD mRNA was increased nearly 3-fold in
      NAFLD patients, compared with patients with normal liver (3.1 +/- 2.6 vs. 1.1 +/-
      1.0 arbitrary units per microgram total RNA, P = 0.026). Finally, overexpressing
      GPI-PLD was associated with an increase in de novo lipogenesis genes.
      CONCLUSIONS: Patients with NAFLD have elevated serum levels and hepatic
      expression of GPI-PLD, and its overexpression in vitro is associated with
      increased expression of de novo lipogenesis genes. These results suggest that GPI
      PLD may play a role in the pathogenesis of NAFLD and/or its metabolic features
      and warrants further investigation.

PMID- 16595595
TI  - The role of endocrine counterregulation for estimating insulin sensitivity from
      intravenous glucose tolerance tests.
AB  - CONTEXT: During insulin-modified frequently sampled iv glucose tolerance tests
      (IM-FSIGT), which allow assessment of insulin action, plasma glucose can markedly
      decrease. OBJECTIVE: This study aimed to assess the counterregulatory impact of
      the insulin-induced fall of glucose on minimal model-derived indices of insulin
      sensitivity (S(I)) and glucose effectiveness. PARTICIPANTS: Thirteen nondiabetic
      volunteers (seven males, six females, aged 26 +/- 1 yr, body mass index 22.1 +/-
      0.7 kg/m(2)) were studied. DESIGN: All participants were studied in random order
      during IM-FSIGT (0.3 g/kg glucose; 0.03 U/kg insulin at 20 min) and during
      identical conditions but with a variable glucose infusion preventing a decrease
      of plasma glucose concentration below euglycemia (IM-FSIGT-CLAMP). Five
      participants additionally underwent euglycemic-hyperinsulinemic (1 mU.kg(-1).min(
      1)) clamp tests. RESULTS: Plasma glucose declined during IM-FSIGT to its nadir of
      50 +/- 3 mg/dl at 60 min in parallel to a rise (P < 0.05 vs. basal) of plasma
      glucagon, cortisol, epinephrine, and GH. Glucose infusion rates of 4.6 +/- 0.5
      mg.kg(-1).min(-1) between 30 and 180 min during IM-FSIGT-CLAMP prevented the
      decline of plasma glucose and the hypoglycemia counterregulatory hormone
      response. S(I) was approximately 68% lower during IM-FSIGT (3.40 +/- 0.36 vs. IM
      FSIGT-CLAMP: 10.71 +/- 1.06 10(-4).min(-1) per microU/ml, P < 0.0001), whereas
      glucose effectiveness did not differ between both protocols (0.024 +/- 0.002 vs.
      0.021 +/- 0.003 min(-1), P = NS). Compared with the euglycemic hyperinsulinemic
      clamp test, S(I) expressed in identical units from IM-FSIGT was approximately 66%
      (P < 0.001) lower but did not differ between the euglycemic hyperinsulinemic
      clamp test and the IM-FSIGT-CLAMP (P = NS). CONCLUSIONS: The transient fall of
      plasma glucose during IM-FSIGT results in lower estimates of S(I), which can be
      explained by hormonal response to hypoglycemia.

PMID- 16595596
TI  - Larger testes and higher inhibin B levels in Finnish than in Danish newborn boys.
AB  - CONTEXT: Recent studies showed that male reproductive health problems, such as
      cryptorchidism, hypospadias, testicular cancer, and low sperm quality, are more
      prevalent in Denmark than in Finland. OBJECTIVES: We hypothesized that, if fetal
      testicular dysgenesis contributed to these observations, differences in gonadal
      development and the hypothalamus-pituitary-testis axis would already be
      detectable perinatally. Thus, we investigated healthy newborn boys in both
      countries. DESIGN: This was a prospective, longitudinal population-based study.
      SETTING: Two primary obstetric centers were included at the University Hospitals
      of Copenhagen, Denmark, and Turku, Finland. PARTICIPANTS: The participants of the
      study included 633 Danish and 1044 Finnish boys, born at term with appropriate
      weight for gestational age. INTERVENTIONS: Ultrasound determination of testis
      size at 0, 3, and 18 months and blood sampling (n = 727) at 3 months were
      analyzed. MAIN OUTCOME MEASURES: Testicular volume and reproductive hormones were
      measured. RESULTS: Testis volume was significantly higher at all ages in Finnish
      than in Danish boys (medians, 98 vs. 95, 185 vs. 119, and 188 vs. 136 mm(3),
      respectively; P < 0.00001). Testis growth from birth to 3 months was larger in
      Finnish than in Danish boys (mean, 75 vs. 26 mm(3); P < 0.0001). Serum hormone
      levels were higher in Finnish than Danish boys for inhibin B (median, 456 vs. 385
      pg/ml; P < 0.0001), FSH (1.33 vs. 1.21 IU/liter; P < 0.036), and SHBG (143 vs.
      136 nmol/liter; P < 0.022). Inhibin B was significantly positively correlated to
      testicular volume (r = 0.25; P < 0.006). CONCLUSIONS: The larger testes and
      higher inhibin B levels most likely represent a bigger volume of seminiferous
      tubules in Finnish compared with Danish boys. Although this phenomenon may be
      attributable to a genetic difference between the two countries, it may also
      reflect environmental factors influencing testicular development.

PMID- 16595597
TI  - The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5'
      triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an
      increased risk of secondary failure to sulfonylurea in patients with type 2
      diabetes.
AB  - CONTEXT: Several studies suggest that genetic factors may play a role in the
      different responses to antidiabetic therapy; however, conclusive evidence is
      still lacking. OBJECTIVE: The objective of the study was to investigate whether
      diabetic patients carrying the E23K variant in KCNJ11 are at increased risk for
      secondary sulfonylurea failure. DESIGN: Secondary sulfonylurea failure was
      defined as fasting plasma glucose greater than 300 mg/dl despite sulfonylurea
      metformin combined therapy and appropriate diet, in the absence of other
      conditions causing hyperglycemia. SETTING: The study was conducted in an
      ambulatory care facility. PATIENTS: A total of 525 Caucasian type 2 diabetic
      patients were enrolled in the study. INTERVENTION: Sulfonylurea treatment was
      followed by sulfonylurea-metformin combined therapy and then insulin treatment.
      MAIN OUTCOME MEASURE: Secondary failure was the main outcome measure. RESULTS: Of
      the diabetic patients enrolled in the study, 38.5% were E23E homozygous, 51.4%
      were E23K heterozygous, and 10.1% were K23K homozygous. The frequency of carriers
      of the K allele was 58 and 66.8% among patients treated with oral therapy or
      secondary sulfonylurea failure, respectively (odds ratio, 1.45; 95% confidence
      interval, 1.01-2.09; P = 0.04). Adjustment for age, gender, fasting glycemia,
      glycosylated hemoglobin, age at diagnosis, and duration of diabetes in a logistic
      regression analysis did not change this association (odds ratio, 1.69; 95%
      confidence interval, 1.02-2.78; P = 0.04). Islets isolated from carriers of the K
      allele showed no differences in glucose-stimulated insulin secretion and a
      tendency toward reduced response upon glibenclamide stimulation (P = 0.09). After
      24-h exposure to high (16.7 mmol/liter) glucose concentration, impairment of
      glibenclamide-induced insulin release was significantly (P = 0.01) worse with the
      E23K variant. CONCLUSIONS: These data suggest that the E23K variant in KCNJ11 may
      influence the variability in the response of patients to sulfonylureas, thus
      representing an example of pharmacogenetics in type 2 diabetes.

PMID- 16595598
TI  - The INS VNTR locus does not associate with smallness for gestational age (SGA)
      but interacts with SGA to increase insulin resistance in young adults.
AB  - CONTEXT: Both adverse intrauterine events and genetic background have been
      suggested to promote insulin resistance in subjects born small for gestational
      age (SGA). Among candidate genes that potentially influence both fetal growth and
      glucose metabolism is insulin. The potential effect of the insulin gene VNTR
      (INS) on birth weight has been controversial so far. OBJECTIVE: The present
      association study aimed at testing for the contribution of the INS VNTR locus on
      birth weight and on the metabolic profile of young adults born SGA (mean age, 22
      yr). Two groups of subjects were selected on birth data: SGA (birth weight < 10th
      percentile; n = 735), and appropriate for gestational age (AGA; birth weight
      between 25th and 75th percentiles; n = 886). All subjects were genotyped for
      rs689 A/T single nucleotide polymorphism, in complete linkage disequilibrium with
      the INS VNTR classes I and III, respectively. RESULTS: Class I INS frequencies
      were similar in the two groups (70% in AGA; 72% in SGA; P = 0.42). There was
      significant effect on mean birth weight in neither SGA (P = 0.99) nor AGA (P =
      0.18). Although the INS VNTR locus did not associate with anomalies of insulin
      resistance indices in the AGA group, in the SGA group, INS VNTR class III allele
      was associated with higher insulin resistance (quantitative insulin sensitivity
      check index = 0.38 vs. 0.39; P = 0.05). Furthermore, there was evidence of an
      interaction between the SGA/AGA status and INS VNTR locus on insulin resistance
      indices (P = 0.01) in a multivariate analysis. CONCLUSION: The INS VNTR locus
      does not associate in a major way with SGA in the French population. However, our
      data support an interaction between severe fetal growth restriction and INS VNTR
      locus, which were associated with insulin resistance in young adults born SGA.

PMID- 16595599
TI  - Randomized, controlled trial of metformin for obesity and insulin resistance in
      children and adolescents: improvement in body composition and fasting insulin.
AB  - CONTEXT: Metformin therapy for adults and children with type 2 diabetes is well
      established. However, its role in the treatment of insulin resistance and obesity
      in children and adolescents is less clearly defined. OBJECTIVE: We assessed the
      effect of metformin on body composition and insulin sensitivity in pediatric
      subjects with exogenous obesity. DESIGN AND SETTING: Patients referred to a
      pediatric endocrine clinic were enrolled in a randomized, double-blind, crossover
      trial. PATIENTS: Twenty-eight patients (13 males) aged 9-18 yr participated in
      the study. INTERVENTION: Patients received metformin (1 g twice daily) and
      placebo for 6 months, each with a 2-wk washout period. MAIN OUTCOME MEASURES:
      Body composition (anthropometry, dual-energy x-ray absorptiometry, and abdominal
      magnetic resonance imaging), and insulin sensitivity (Si; minimal model, fasting
      insulin and glucose) were measured at baseline and 6 and 12 months. RESULTS: Mean
      age of subjects at baseline was 12.5 +/- 2.2 yr, median body mass index z-score
      2.54 (range, 1.93-2.85). Metformin had a greater treatment effect over placebo
      for weight (-4.35 kg, P = 0.02), body mass index (-1.26 kg/m(2), P = 0.002),
      waist circumference (-2.8 cm, P = 0.003), sc abdominal adipose tissue (-52.5
      cm(2), P = 0.002), and fasting insulin (-2.2 mU/liter, P = 0.011). Si improved in
      45% of subjects while on metformin and 27% of subjects while on placebo (P =
      0.21). CONCLUSIONS: Metformin therapy for obese insulin-resistant pediatric
      patients results in significant improvement in body composition and fasting
      insulin. Although improvement in Si was noted in many individuals, Si was a less
      useful parameter for analysis of group data, possibly because of effects of
      variable compliance and changing Si during puberty.

PMID- 16595600
TI  - Thyrotoxicosis after denileukin diftitox therapy in patients with mycosis
      fungoides.
AB  - CONTEXT: Denileukin diftitox is a recombinant novel fusion protein of diphtheria
      toxin and the ligand-binding domain of human IL-2. Denileukin diftitox binds to
      the high-affinity IL-2 receptor on the cell surface, and it is internalized by
      endocytosis and enzymatically cleaved. The cytotoxic A-fragment of the toxin
      inhibits protein synthesis and causes cell death. OBJECTIVE: The objective of
      this study was to recognize thyrotoxicosis in association with denileukin
      diftitox therapy. DESIGN: This study was a retrospective case series. SETTING:
      The setting of this study was a comprehensive cancer center. PATIENTS: Eight
      mycosis fungoides patients who were receiving 9 or 18 microg/kg.d iv denileukin
      diftitox for 5 d every 3 wk were identified with thyrotoxicosis. INTERVENTION(S):
      Thyroid testing was performed. Hypothyroidism after thyrotoxicosis was treated.
      RESULTS: In eight mycosis fungoides patients who developed transient
      thyrotoxicosis during therapy, thyroid function tests were normal before onset of
      therapy. Clinical thyrotoxicosis developed within days of the first cycle of
      denileukin diftitox therapy in four patients and after the second cycle in the
      other four patients. Symptoms included tremors, nervousness, tachycardia,
      diarrhea, and weight loss. After cessation of denileukin diftitox, thyrotoxicosis
      resolved in all patients; two became euthyroid, and five became hypothyroid,
      requiring levothyroxine therapy. One patient was lost to follow-up. CONCLUSIONS:
      Monitoring thyroid function before and during treatment with denileukin diftitox
      is recommended. Symptomatic thyrotoxicosis may be missed due to other acute
      reactions to the drug, and subsequent hypothyroidism may develop.

PMID- 16595601
TI  - antiphospholipid antibodies syndrome associated with hyperhomocysteinemia related
      to MTHFR Gene C677T and A1298C heterozygous mutations in a young man with
      idiopathic hypoparathyroidism (DiGeorge syndrome).
AB  - CONTEXT: Antiphospholipid syndrome (APS, or Hughes' syndrome) is a systemic
      autoimmune disorder characterized by antiphospholipid antibody positivity, which
      may lead to arterial and/or venous thrombosis. Hyperhomocysteinemia (HHcy),
      variously associated with 5,10-methylene tetrahydrofolate reductase (MTHFR) gene
      point mutations, is also implicated in thromboembolic events. The association of
      APS and HHcy has already been described but has never been reported in patients
      with DiGeorge syndrome (DGS), the most common contiguous-gene deletion syndrome
      (22q11.2) in humans, whose phenotype conversely includes bleeding disorders. DATA
      ACQUISITION: In this report, we present the case of a 19-yr-old patient with a
      past medical history of learning disability and obesity affected with idiopathic
      hypoparathyroidism, metabolic syndrome, and diffuse vasculitis disorders. He was
      referred to our endocrinology clinic for the management of severe hypocalcemia.
      At the time of presentation he had been taking antiepileptic drugs for 2 wk and
      displayed facial dysmorphism (short neck, micrognathia, a small mouth,
      hypoplastic nasal alae, eye hypertelorism, and low-set simple ears). DGS was
      suspected and confirmed by both fluorescence in situ hybridization analysis and
      single nucleotide polymorphism-array analysis, which revealed contiguous gene
      microdeletion of the chromosome 22q11.2 in the minimal DiGeorge critical region,
      specifically at the gene locus D22S75 (N25). CONCLUSIONS: APS, revealed by anti
      beta-2-glycoprotein and anti-prothrombin antibodies positivity, and moderate HHcy
      related to heterozygous C677T and A1298C point mutations of the MTHFR gene were
      identified as a possible cause of thrombotic disorder responsible for the
      widespread presence of cutaneous and cerebral lesions.

PMID- 16595602
TI  - Thyrotropin receptor epitopes and their relation to histocompatibility leukocyte
      antigen-DR molecules in Graves' disease.
AB  - CONTEXT: Graves' disease (GD) is characterized by autoimmunity to the TSH
      receptor (TSHR). OBJECTIVE: We sought to identify T cell epitopes in TSHR that
      initiate this immune response and their interaction with human histocompatibility
      leukocyte antigen (HLA) molecules predisposing to GD. DESIGN: We examined the
      affinity of 31 overlapping peptides spanning the TSHR extracellular domain for
      binding in vitro to five purified HLA-DR molecules; DRB1*0101 (DR1), DRB1*1501
      (DR2), DRB1*0301 (DR3), DRB1*1101 (DR5), and DRB1*0701 (DR7). We scanned the TSHR
      extracellular domain using a T cell epitope-mapping algorithm, EpiMatrix. We
      compared these results with clinical studies of GD patients measuring in vitro T
      cell responses to the peptides. SETTING: The study was conducted at a university
      laboratory. PATIENTS: Patients included 200 serial adult clinic patients with GD.
      INTERVENTION: There were no interventions. MAIN OUTCOME MEASUREMENTS: Binding
      affinity of epitopes, predicted affinity, and reported T cell stimulation data
      were measured. RESULTS: Most peptides bound with intermediate or high affinity to
      one or more HLA-DR molecule. Peptides binding to HLA-DR3 and HLA-DR5, which
      predispose to GD, exhibited moderate binding affinities overall, whereas most
      peptides binding to GD-protective HLA-DR7 bound with high affinity. These
      differences may relate to T cell selection in the thymus. Binding affinity of
      peptides correlated strongly with EpiMatrix-predicted affinity for HLA-DRB1*0101,
      DRB1*1501, DR3, and DRB1*0701 but not HLA-DR5. Average IC(50) values correlated
      significantly with clinical T cell stimulation data. CONCLUSIONS: Three different
      methods for identifying immunogenic peptides did not provide a uniform picture of
      important TSHR epitopes. However, peptide 132-150 (GIFNTGLKMFPDLTKVYST) was
      identified by three methods as an important epitope in GD; the possible
      importance of peptides 145-163, 158-176, 207-222, 248-263, 272-291, and 343-362
      was also identified.

PMID- 16595603
TI  - Regulation of vascular endothelial growth factor synthesis and release by human
      luteal cells in vitro.
AB  - CONTEXT: Vascular endothelial growth factor (VEGF) is essential for normal luteal
      development and function, but little is still known about the regulation of its
      production by human midluteal phase luteal cells. OBJECTIVE: We investigated
      whether human chorionic gonadotropin (hCG) or local factors, including chemical
      hypoxia, IGF-I and IGF-II, prostaglandin (PG)E(2), and PGF(2alpha) prevail in
      modulating VEGF mRNA and protein production in human midluteal phase luteal
      cells. The effect of progesterone (P) on luteal VEGF mRNA expression and protein
      secretion was also evaluated. Finally, we investigated whether VEGF could
      directly affect luteal P secretion. INTERVENTIONS: In human midluteal phase
      luteal cells, VEGF mRNA expression was evaluated by semiquantitative RT-PCR,
      whereas VEGF and P release was evaluated by ELISA and RIA, respectively. RESULTS:
      hCG was unable to significantly affect luteal VEGF mRNA and protein synthesis,
      which in turn was significantly increased by both chemical hypoxia and IGFs.
      Conversely, VEGF mRNA and protein production was reduced by PGs and P. Finally,
      VEGF did not affect P luteal secretion. CONCLUSIONS: Our results suggest that
      local ovarian factors, rather than hCG, predominate in regulating VEGF mRNA and
      protein production by human midluteal phase luteal cells. For VEGF, a lack of a
      direct luteal steroidogenic effect was also demonstrated.

PMID- 16595604
TI  - Cortistatin inhibits growth hormone release from human fetal and adenoma
      pituitary cells and prolactin secretion from cultured prolactinomas.
AB  - CONTEXT: Cortistatin (CST) is a neuropeptide that shares high homology with
      somatostatin and binds with high affinity to all somatostatin receptor (SSTR)
      subtypes. Many of its endocrine and biological activities overlap with those of
      somatostatin. OBJECTIVE/DESIGN: The objective of the study was to assess the
      direct in vitro effects of CST on human pituitary hormone secretion. SETTING:
      This study was performed in the endocrine laboratory of a tertiary academic
      medical center. MATERIALS: Primary cell cultures of human fetal (21-25 wk
      gestation) pituitary tissues and cultured hormone-secreting adenoma cells were
      used in this study. INTERVENTIONS: Cell cultures were incubated with CST-14 or
      CST-17, somatostatin, GHRH, SSTR analogs, and ghrelin analogs, and hormone
      secretion was analyzed. OUTCOME MEASURES: GH and prolactin (PRL) medium
      concentrations were tested by hormone assay, and SSTR mRNA was tested by RT-PCR.
      RESULTS: CST-14 (10 nm) inhibited GH secretion by up to 65% in all fetal
      pituitary specimens after 4-h incubation (P < 0.05). CST-14 or CST-17 (10 nm)
      inhibited basal GH secretion in six of the 13 GH-cell adenomas and two of the
      three GH-PRL mixed adenomas. CST-17 (100 nm) suppressed the GH response to GHRH
      and ghrelin analog (10 nm each) by 30-50% in adenomas (P < 0.05). Three PRL
      adenomas treated with CST-17 (10 nm) showed a 20-40% inhibition of PRL release (P
      < 0.05), whereas in three others no suppression or mild response was achieved at
      this concentration. A comparable inhibition of PRL secretion was obtained with
      SSTR5-selective analog but significantly less with SSTR2-preferential compounds.
      RT-PCR revealed the expression of both SSTR2 and SSTR5 in all GH-cell and mixed
      adenomas studied and all PRL-secreting adenomas studied, except for two of the
      CST-resistant prolactinomas, in which SSTR5 was absent. CONCLUSIONS: This is the
      first report of in vitro CST suppression of human GH and PRL in cultured
      pituitary tissues. The regulation of PRL release from cultured adenomas appears
      to be primarily mediated by SSTR5.

PMID- 16595605
TI  - Phytoestrogens and lipoproteins in women.
AB  - OBJECTIVES: We undertook a study to evaluate relationships among blood
      phytoestrogen levels, lipoprotein levels, estrogen levels, and angiographically
      defined coronary artery disease in women. BACKGROUND: Evidence for a beneficial
      role and the potential mechanism(s) of plant estrogens (phytoestrogens) on blood
      lipoproteins in humans is controversial. METHODS: We evaluated 483 women enrolled
      in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia
      Syndrome Evaluation with coronary risk factors undergoing coronary angiography
      for evaluation for suspected ischemia for blood phytoestrogen levels (daidzein
      and genistein), lipoprotein levels [total cholesterol, triglycerides, low-density
      lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-C)], estrogen
      levels (estradiol, bioavailable estradiol, estrone), and angiographic coronary
      artery disease using core laboratories. RESULTS: Higher blood levels of the
      phytoestrogen daidzein were associated with lower triglycerides (P = 0.01),
      higher HDL-C (P = 0.05) levels, and a beneficial total cholesterol to HDL-C ratio
      (P = 0.02). This beneficial association was evident among the subgroup of women
      with low [<184 pmol/liter (<50 pg/ml)] blood estradiol levels, regardless of age
      and lipoprotein levels. The phytoestrogen associations with lipoproteins were
      incrementally related to the magnitude of daidzein level and independent of other
      lipoprotein modulators. There were no detectable relationships between the
      phytoestrogen levels and angiographic coronary artery disease. CONCLUSIONS:
      Higher blood phytoestrogen daidzein levels are associated with beneficial
      lipoprotein levels in women with low estrogen levels, possibly by an estrogen
      receptor mechanism. These results suggest a potential explanation for the
      variable lipoprotein results observed in prior randomized controlled trials and
      call for investigation regarding subgroups of subjects who may preferentially
      benefit from dietary intake of food products, such as soy.

PMID- 16595606
TI  - Genetic linkage of hyperglycemia, body weight and serum amyloid-P in an
      intercross between C57BL/6 and C3H apolipoprotein E-deficient mice.
AB  - Dyslipidemia and hyperglycemia are integral components of the metabolic
      perturbations in type 2 diabetes. Apolipoprotein E-deficient (apoE(-/-)) mice
      develop severe hyperlipidemia and significant hyperglycemia when fed a western
      diet containing 21% fat (w/w), 0.15% cholesterol and 19.5% casein. Using an
      intercross between C57BL/6J (B6) and C3H/HeJ (C3H) apoE(-/-) mice, we performed
      quantitative trait locus (QTL) analysis to identify loci contributing to
      hyperglycemia and associated traits. Fasting plasma levels of glucose, insulin
      and serum amyloid-P (SAP) and body weight in 234 female F2 mice were measured
      after being fed the western diet for 12 weeks. QTL analysis revealed one
      significant QTL, named Bglu3 [95.8 cM, logarithm of odds ratio (OR)(LOD) 4.1], on
      chromosome 1 and a suggestive QTL on chromosome 9 (38 cM, LOD 2.3) that
      influenced plasma glucose levels. Bglu3 coincided with loci on distal chromosomal
      1 that had a major influence on plasma SAP levels and body weight. Significant
      correlations between plasma glucose, SAP and body weight were observed in F2
      mice. Thus, these results demonstrate genetic linkages of hyperglycemia and body
      weight with SAP, a marker of the acute-phase response, in hyperlipidemic apoE(-/
      ) mice and suggest a probability for the Sap gene to be a positional candidate of
      Bglu3.

PMID- 16595608
TI  - Naturally occurring utrophin correlates with disease severity in Duchenne
      muscular dystrophy.
AB  - Although there is good experimental data that utrophin, the autosomal analog of
      dystrophin, can ameliorate the phenotype in dystrophinopathies, there is scant
      evidence from human data to support this hypothesis. We investigated in
      diagnostic muscle biopsies from 16 patients with Duchenne muscular dystrophy
      (DMD) the level of utrophin expression using quantitative immunoblot analysis. In
      13 of 16 patients, in whom there was adequate follow-up data, utrophin expression
      was correlated to two clinical endpoints: age at reaching Hammersmith score of
      30/40 and age at becoming wheelchair-bound. We found that utrophin expression
      increases with age in DMD and that there is a significant positive correlation
      between the quantity of utrophin at initial biopsy and time to becoming
      wheelchair-bound.

PMID- 16595609
TI  - A highly functional mini-dystrophin/GFP fusion gene for cell and gene therapy
      studies of Duchenne muscular dystrophy.
AB  - A promising approach for treating Duchenne muscular dystrophy (DMD) is by
      autologous cell transplantation of myogenic stem cells transduced with a
      therapeutic expression cassette. Development of this method has been hampered by
      a low frequency of cellular engraftment, the difficulty of tracing transplanted
      cells, the rapid loss of autologous cells carrying marker genes that are unable
      to halt muscle necrosis and the difficulty of stable transfer of a large
      dystrophin gene into myogenic stem cells. We engineered a 5.7 kb miniDys-GFP
      fusion gene by replacing the dystrophin C-terminal domain (DeltaCT) with an eGFP
      coding sequence and removing much of the dystrophin central rod domain (DeltaH2
      R19). In a transgenic mdx(4Cv) mouse expressing the miniDys-GFP fusion protein
      under the control of a skeletal muscle-specific promoter, the green fusion
      protein localized on the sarcolemma, where it assembled the dystrophin
      glycoprotein complex and completely prevented the development of dystrophy in
      transgenic mdx(4Cv) muscles. When myogenic and other stem cells from these mice
      were transplanted into mdx(4Cv) recipients, donor cells can be readily identified
      in skeletal muscle by direct green fluorescence or by using antibodies against
      GFP or dystrophin. In mdx(4Cv) mice reconstituted with bone marrow cells from the
      transgenic mice, we monitored engraftment in various muscle groups and found the
      number of miniDys-GFP(+) fibers increased with time. We suggest that these
      transgenic mdx(4Cv) mice are highly useful for developing autologous cell
      therapies for DMD.

PMID- 16595607
TI  - Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart
      disease: The Atherosclerosis Risk in Communities (ARIC) study.
AB  - Endothelial dysfunction contributes to the development of coronary heart disease
      (CHD). Soluble epoxide hydrolase metabolizes epoxyeicosatrienoic acids in the
      vasculature and regulates endothelial function. We sought to determine whether
      genetic variation in soluble epoxide hydrolase (EPHX2) was associated with the
      risk of CHD. We genotyped 2,065 Atherosclerosis Risk in Communities study
      participants (1,085 incident CHD cases, 980 non-cases) for 10 previously
      identified polymorphisms in EPHX2. Using a case-cohort design, associations
      between incident CHD risk and both non-synonymous EPHX2 polymorphisms and phase
      reconstructed haplotypes were evaluated using proportional hazards regression.
      Individuals carrying the K55R polymorphism variant allele demonstrated higher
      apparent soluble epoxide hydrolase activity in vivo. Presence of the K55R variant
      allele was significantly more common among Caucasian CHD cases when compared with
      non-cases (20.8% versus 15.3%, respectively, P=0.012), and was associated with
      significantly higher risk of incident CHD (adjusted hazard rate ratio 1.45, 95%
      confidence interval 1.05-2.01, P=0.026). A significant association between the
      K55R variant allele and risk of CHD was not observed in African-Americans. The
      distribution of reconstructed haplotypes were significantly different in
      Caucasian cases when compared with non-cases (P=0.021). Significant differences
      in haplotype distribution were not observed in African-Americans (P=0.315).
      Genetic variation in EPHX2 was significantly associated with risk of incident CHD
      in Caucasians, implicating EPHX2 as a potential cardiovascular disease
      susceptibility gene.

PMID- 16595610
TI  - C-termini of P/Q-type Ca2+ channel alpha1A subunits translocate to nuclei and
      promote polyglutamine-mediated toxicity.
AB  - P/Q-type voltage-gated calcium channels are regulated, in part, through the
      cytoplasmic C-terminus of their alpha1A subunit. Genetic absence or alteration of
      the C-terminus leads to abnormal channel function and neurological disease. Here,
      we show that the terminal 60-75 kDa of the endogenous alpha1A C-terminus is
      cleaved from the full-length protein and is present in cell nuclei. Antiserum to
      the C-terminus (CT-2) labels both wild-type mouse and human Purkinje cell nuclei,
      but not leaner mouse cerebellum. Human embryonic kidney cells stably expressing
      beta3 and alpha2delta subunits and transiently transfected with full-length human
      alpha1A contain a 75 kDa CT-2 reactive peptide in their nuclear fraction. Primary
      granule cells transfected with C-terminally Green fluorescent protein (GFP)
      tagged alpha1A exhibit GFP nuclear labeling. Nuclear translocation depends partly
      on the presence of three nuclear localization signals within the C-terminus. The
      C-terminal fragment bears a polyglutamine tract which, when expanded (Q33) as in
      spinocerebellar ataxia type 6 (SCA6), is toxic to cells. Moreover, polyglutamine
      mediated toxicity is dependent on nuclear localization. Finally, in the absence
      of flanking sequence, the Q33 expansion alone does not kill cells. These results
      suggest a novel processing of the P/Q-type calcium channel and a potential
      mechanism for the pathogenesis of SCA6.

PMID- 16595611
TI  - Dexmedetomidine vs midazolam for monitored anaesthesia care during cataract
      surgery.
AB  - BACKGROUND: Cataract surgery is commonly performed under local anaesthesia with
      midazolam sedation. Dexmedetomidine, a sedative-analgesic, is devoid of
      respiratory depressant effects, and its use in cataract surgery has not been
      reported. This double-blind study compared the use of dexmedetomidine and
      midazolam in patients undergoing cataract surgery. METHODS: Forty-four patients
      undergoing cataract surgery under peribulbar anaesthesia randomly received either
      i.v. dexmedetomidine 1 microg kg(-1) over 10 min; followed by 0.1-0.7 microg kg(
      1) h(-1) i.v. infusion (Group D), or midazolam 20 microg kg(-1) i.v.; followed by
      0.5 mg i.v. boluses as required (Group M). Sedation was titrated to a Ramsay
      sedation score of 3. Mean arterial pressure (MAP), heart rate (HR), readiness for
      recovery room discharge (time to Aldrete score of 10), and patients' and
      surgeons' satisfaction (on a scale of 1-7) were determined. RESULTS: MAP and HR
      were lower in Group D compared with Group M [86 (se 3) vs 102 (3) mm Hg and 65
      (2) vs 72 (2) beats min(-1), respectively] (P<0.05). Group D patients had
      slightly higher satisfaction with sedation [median (IQR): 6 (6-7) vs 6 (5-7),
      P<0.05], but delayed readiness for discharge [45 (36-54) vs 21 (10-32) min,
      P<0.01] compared with patients in Group M. Surgeons' satisfaction was comparable
      in both groups [5 (4-6) vs 5 (4-6)]. CONCLUSION: Compared with midazolam,
      dexmedetomidine does not appear to be suitable for sedation in patients
      undergoing cataract surgery. While there was a slightly better subjective patient
      satisfaction, it was accompanied by relative cardiovascular depression and
      delayed recovery room discharge.

PMID- 16595612
TI  - Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of
      pathophysiology and clinical management.
AB  - Since the late 1980s 'Ecstasy' (3,4-methylenedioxymethamphetamine, MDMA) has
      become established as a popular recreational drug in western Europe. The UK
      National Criminal Intelligence Service estimates that 0.5-2 million tablets are
      consumed weekly in Britain. It has been reported that 4.5% of young adults (15-34
      yr) in the UK have used MDMA in the previous 12 months. Clinically important
      toxic effects have been reported, including fatalities. While the phenomenon of
      hyperpyrexia and multi-organ failure is now relatively well known, other serious
      effects have become apparent more recently. Patients with acute MDMA toxicity may
      present to doctors working in Anaesthesia, Intensive Care and Emergency Medicine.
      A broad knowledge of these pathologies and their treatment is necessary for
      anyone working in an acute medical speciality. An overview of MDMA pharmacology
      and acute toxicity will be given followed by a plan for clinical management.

PMID- 16595613
TI  - Changes in creatine phosphokinase (CK) concentrations after minor and major
      surgeries in children.
AB  - BACKGROUND: During surgery, damage occurs to muscles in the area of the
      operation. The few studies that have examined creatine phosphokinase (CK) values
      after surgery have been in adults. The only study in children was after cardiac
      surgery. Understanding the normal enzyme pattern of change may help to
      differentiate malignant hyperthermia, anaesthesia-induced rhabdomyolysis and
      elevated CK values resulting from inherited muscle disease in cases in which
      these are suspected. The aim of this study was to delineate the normal rise of CK
      after minor and major surgery in children. METHODS: A total of 71 patients aged 1
      month-17 yr were studied. From the cohort of 71 patients, 46 underwent elective
      surgery (14 major, 32 minor) and in 25 the surgery was designated as an emergency
      surgery (21 major, 4 minor). The anaesthesia protocol was similar for both groups
      with halothane induction and isoflurane maintenance. Owing to its possible effect
      on CK, succinylcholine was avoided during the study. RESULTS: The mean values of
      CK concentration before and after surgery were 63.1 iu litre(-1) and 151.5 iu
      litre(-1), respectively. The median CK elevation (range) for the major and minor
      surgery groups was 43 iu litre(-1) (4-647) and 10 iu litre(-1) (-28 to 122),
      respectively (P<0.0001). CONCLUSIONS: CK concentrations in the major surgery
      group were significantly higher than the minor surgery group. This profile can
      contribute to the evaluation of patients who present with the possibility of
      malignant hyperthermia, anaesthesia-induced rhabdomyolysis and underlying muscle
      disease. Any rise of CK concentration above what is expected should prompt
      further investigation.

PMID- 16595614
TI  - Gabapentin attenuates the pressor response to direct laryngoscopy and tracheal
      intubation.
AB  - BACKGROUND: Laryngoscopy and tracheal intubation increase blood pressure and
      heart rate (HR). The aim of the present study was to investigate the effect of
      gabapentin when given before operation on the haemodynamic responses to
      laryngoscopy and intubation. METHODS: Forty-six patients undergoing abdominal
      hysterectomy for benign disease were randomly allocated to receive gabapentin
      1,600 mg or placebo capsules at 6 hourly intervals starting the day (noon) before
      surgery. Anaesthesia was induced with propofol and cis-atracurium. Systolic,
      diastolic arterial blood pressures (SAP, DAP) and heart rate (HR) were recorded
      before and after the anaesthetic and 0, 1, 3, 5 and 10 min after tracheal
      intubation. RESULTS: SAP was significantly lower in the gabapentin vs the control
      group 0, 1, 3, 5 and 10 min after intubation [128 (27) vs 165 (41), P=0.001, 121
      (14) vs 148 (29), P=0.0001, 115 (13) vs 134 (24), P=0.002, 111 (12) vs 126 (19),
      P=0.004 and 108 (12) vs 124 (17), P=0.001 respectively]. DAP also was lower in
      the gabapentin group 0, 1, 3, and 10 min after intubation [81 (18) vs 104 (19),
      P=0.0001, 77 (9) vs 91 (16), P=0.001, 71 (10) vs 84 (13), P=0.001 and 67 (10) vs
      79 (12), P=0.004]. HR did not differ between the two groups at any time [82 (11)
      vs 83 (15), 79 (10) vs 80 (12), 86 (17) vs 92 (10), 82 (11) vs 88 (10), 81 (12)
      vs 81 (11), 77 (13) vs 79 (13), and 75 (15) vs 78 (12)]. CONCLUSION: Gabapentin,
      under the present study design attenuates the pressor response but not the
      tachycardia associated with laryngoscopy and tracheal intubation.

PMID- 16595615
TI  - Effects of increased intra-abdominal pressure on central circulation.
AB  - BACKGROUND: In an experimental model we investigated the effects of a gradual
      increase in intra-abdominal pressure (IAP) on the central circulation. METHODS:
      Seven pigs were anaesthetized, mechanically ventilated and instrumented. IAP was
      gradually increased by 5 mm Hg up to 30 mm Hg by abdominal banding in
      normovolaemic animals, and then they were made hypovolaemic after blood
      withdrawal. Right atrial pressure (RAP) and left ventricular end-diastolic
      pressure (LVEDP) at each step and aortic, femoral and inferior vena cava blood
      flows were measured. Left ventricular end-diastolic area (LVEDA) was determined
      using epicardial echocardiography. RESULTS: Cardiac output maintained at mild IAP
      was reduced to 76 (24)% of the initial value at 30 mm Hg IAP [mean (sd)] in
      normovolaemic animals, and 72 (22)% (P<0.001) in hypovolaemic animals. In
      normovolaemic animals the LVEDA and LVEDP were significantly increased at an IAP
      of 10 and 15 mm Hg by 26 (24)% and 38 (23)%, respectively. At these IAP values,
      the difference between the RAP and IAP was positive. When this gradient became
      negative, that is beyond 15 mm Hg in normovolaemia and for all IAP values in
      hypovolaemic animals, the LVEDA declined, reaching 78 (16)% and 62 (22)% (P<0.05)
      of the initial values in normovolaemic and hypovolaemic groups at the highest IAP
      value. CONCLUSIONS: These results showed that a gradual increase in IAP led to a
      redistribution of abdominal blood volume towards the thoracic compartment, at IAP
      lower than 15 mm Hg in normovolaemia, and at its expense at higher values of IAP.
      In hypovolaemia there was no thoracic compartment gain. Whereas the absolute or
      transmural RAPs were not informative of the direction of this blood shift, an RAP
      greater than IAP was associated with an intrathoracic compartment gain.

PMID- 16595616
TI  - Preconditioning effects of levosimendan in coronary artery bypass grafting--a
      pilot study.
AB  - BACKGROUND: The calcium sensitizer levosimendan protects against myocardial
      ischaemia and reperfusion injury in animal models. METHODS: The present pilot
      study investigated whether a short infusion before coronary artery bypass
      grafting (CABG) would protect the myocardium and improve postoperative
      haemodynamics. Twenty-four patients with stable angina undergoing elective CABG
      surgery were randomized to receive either placebo or levosimendan (24 microg kg(
      1)) infused i.v. over a 10 min period just before placing the patient on
      cardiopulmonary bypass. RESULTS: Perioperative haemodynamic variables,
      concentrations of cardiac troponin I over the 48 h postoperative period, and
      clinical outcomes were assessed. There were no adverse effects related to
      levosimendan. Compared with control patients, levosimendan-treated patients had
      lower postoperative troponin I concentrations (P<0.05) and a higher cardiac index
      (P<0.05). CONCLUSION: Patients receiving a short infusion of levosimendan before
      CABG showed evidence of less myocardial damage, suggestive of a preconditioning
      effect. Larger outcome studies are thus indicated to confirm benefit.

PMID- 16595617
TI  - Level of consciousness affects the excitability of spinal motor neurones during
      propofol sedation in humans.
AB  - BACKGROUND: To investigate the relationship between the depression of spinal
      motor neuronal excitability and the sedative level induced by propofol infusion,
      we simultaneously analysed the suppressive effect of propofol on the F wave and
      the sedative level during propofol infusion. METHODS: After spinal anaesthesia,
      sedation was achieved using a propofol target-controlled infusion (TCI) system to
      achieve a score of 4 on the Wilson sedation scale. The excitability of spinal
      motor neurones was determined by measuring the left median nerve F wave. F-wave
      persistence and the F/M ratio were recorded at pre-sedation as the control,
      during sedation, at arousal by mild physical stimulation and at post-sedation.
      RESULTS: Wilson sedation scores increased significantly corresponding to the
      increase in the target propofol concentration (Cpt), and a Cpt-producing Wilson
      sedation scale 4 ranged between 1.2 and 1.8 microg ml(-1). The F-wave persistence
      and F/M ratio before propofol infusion were 80.7 (8.6)% and 9.5 (3.9)%,
      respectively. At Wilson sedation scale 4, F-wave persistence and F/M ratio were
      17.6 (12.8)% (0-37.5%) and 4.3 (4.1)%, and, at return of consciousness by mild
      physical stimulation, significantly increased to 71.3 (7.9)% and 10.0 (5.0)%,
      respectively. CONCLUSION: We demonstrated that the excitability of spinal motor
      neurones was suppressed during sedation by propofol TCI, but this suppressive
      effect vanished at return of consciousness by mild physical stimulation even at a
      constant Cpt. Our data suggested that the effect of propofol on the excitability
      of spinal motor neurones might be affected by consciousness level rather than
      propofol Cpt in humans.

PMID- 16595618
TI  - Apolipoprotein E epsilon4 and impaired episodic memory in community-dwelling
      elderly people: a marked sex difference. The Hordaland Health Study.
AB  - BACKGROUND: Among elderly people without dementia, the apolipoprotein E epsilon4
      allele (APOE4) has been associated with cognitive deficit, particularly in
      episodic memory, but few reports are available on whether this association
      differs by sex. METHODS: In a community-dwelling Norwegian cohort of 2181 elderly
      people (55% women), aged 70-74 years, episodic memory was examined in relation to
      sex and APOE4 zygosity, with the Kendrick Object Learning Test (KOLT). RESULTS:
      Possession of at least one APOE4 allele had a modest, detrimental effect on
      episodic memory in women, whereas in men, heterozygotes were unaffected and
      homozygotes had markedly lower scores across the distribution of KOLT scores.
      This sex difference was found consistently in all analyses: on comparing means
      and medians, examining trends across quintiles, and studying the distribution of
      scores and the risk of cognitive impairment. Results were broadly similar when
      adjusted for known determinants of cognition and also when severely impaired
      participants were excluded. The adjusted odds ratio (OR) of cognitive impairment
      in women was shown to be 1.8 (95% confidence interval (CI): 1.1 to 2.8) for
      heterozygotes and 1.1 (0.3 to 3.7) for homozygotes; the adjusted OR in men was
      observed to be 1.1 (0.6 to 2.1) for heterozygotes and 10.7 (4.7 to 24) for
      homozygotes. CONCLUSIONS: Although the harmful effect of APOE4 on episodic memory
      was modest in women, the risk was found to occur in about 30%. APOE4 was observed
      to have a dramatic effect on episodic memory in men, but only in homozygotes, who
      comprised about 3% of men: the whole male homozygous group showed a marked shift
      to lower memory scores.

PMID- 16595619
TI  - Worksite intervention effects on physical health: a randomized controlled trial.
AB  - Overweight and physical inactivity are risk factors for increased disease burden
      and health care expenditure. Well-designed studies are still needed to determine
      the treatment efficacy of worksite interventions targeting such risk factors.
      This randomized controlled trial was conducted at one of Australia's casinos in
      2002-2003, to investigate the effects of a comprehensive exercise and lifestyle
      intervention on physical fitness. Only 6.4% of the workforce expressed interest
      in being study participants. Seventy-three employees (aged 32 +/- 8 years, 51%
      overweight/obese, 73% shift workers and 52% women) were recruited and randomized
      to treatment or wait-list control groups for 24 weeks, 44 of whom completed the
      intervention. Components of the intervention include supervised moderate-to-high
      intensity exercise including combined aerobic (at least 20 min duration 3
      days/week) and weight-training (for an estimated 30 min completed 2-3 days/week),
      and dietary/health education (delivered via group seminars, one-on-one
      counselling and literature through the provision of a worksite manual). ANCOVA,
      by intention-to-treat and of study completers, found significant between-group
      differences in the mean waist circumference and predicted maximal oxygen uptake
      (VO2max), favouring the intervention, but effects were concentrated in one
      subject. For study completers, between-group differences in the mean waist
      circumference (82.3 +/- 9.2 versus 90.5 +/- 17.8 cm, p = 0.01) and predicted
      VO2max (47 versus 41 ml/kg/min, p < 0.001) remained significant without the
      outlier, favouring the intervention. Higher intervention compliance predicted
      greater improvements in physical fitness. No significant effects on body mass or
      body mass index were found. This worksite intervention significantly improved
      waist circumference and aerobic fitness in healthy but sedentary employees, most
      of whom were shift workers. Worksite interventions have the potential to counter
      the increasing burden of overweight and obesity, particularly visceral adiposity,
      as well as physical inactivity; however, substantial barriers to
      adoption/adherence need to be overcome for greater feasibility and impact on
      employee physical health.

PMID- 16595621
TI  - In memoriam: PNAS Editor-in-Chief Nicholas R. Cozzarelli (1938-2006).

PMID- 16595623
TI  - Malaria risk and temperature: influences from global climate change and local
      land use practices.

PMID- 16595622
TI  - Rqh1 blocks recombination between sister chromatids during double strand break
      repair, independent of its helicase activity.
AB  - Many questions remain about the process of DNA double strand break (DSB) repair
      by homologous recombination (HR), particularly concerning the exact function
      played by individual proteins and the details of specific steps in this process.
      Some recent studies have shown that RecQ DNA helicases have a function in HR. We
      studied the role of the RecQ helicase Rqh1 with HR proteins in the repair of a
      DSB created at a unique site within the Schizosaccharomyces pombe genome. We
      found that DSBs in rqh1(+) cells, are predominantly repaired by interchromosomal
      gene conversion, with HR between sister chromatids [sister-chromatid conversion
      (SCC)], occurring less frequently. In Deltarqh1 cells, repair by SCC is favored,
      and gene conversion rates slow significantly. When we limited the potential for
      SCC in Deltarqh1 cells by reducing the length of the G2 phase of the cell cycle,
      DSB repair continued to be predominated by SCC, whereas it was essentially
      eliminated in wild-type cells. These data indicate that Rqh1 acts to regulate DSB
      repair by blocking SCC. Interestingly, we found that this role for Rqh1 is
      independent of its helicase activity. In the course of these studies, we also
      found nonhomologous end joining to be largely faithful in S. pombe, contrary to
      current belief. These findings provide insight into the regulation of DSB repair
      by RecQ helicases.

PMID- 16595624
TI  - Defined culture conditions of human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) are pluripotent cells that have the potential
      to differentiate into any tissue in the human body; therefore, they are a
      valuable resource for regenerative medicine, drug screening, and developmental
      studies. However, the clinical application of hESCs is hampered by the
      difficulties of eliminating animal products in the culture medium and/or the
      complexity of conditions required to support hESC growth. We have developed a
      simple medium [termed hESC Cocktail (HESCO)] containing basic fibroblast growth
      factor, Wnt3a, April (a proliferation-inducing ligand)/BAFF (B cell-activating
      factor belonging to TNF), albumin, cholesterol, insulin, and transferrin, which
      is sufficient for hESC self-renewal and proliferation. Cells grown in HESCO were
      maintained in an undifferentiated state as determined by using six different stem
      cell markers, and their genomic integrity was confirmed by karyotyping. Cells
      cultured in HESCO readily form embryoid bodies in tissue culture and teratomas in
      mice. In both cases, the cells differentiated into each of the three cell
      lineages, ectoderm, endoderm, and mesoderm, indicating that they maintained their
      pluripotency. The use of a minimal medium sufficient for hESC growth is expected
      to greatly facilitate clinical application and developmental studies of hESCs.

PMID- 16595625
TI  - Breaking an impasse in pectin biosynthesis.

PMID- 16595627
TI  - A hidden metabolic pathway exposed.

PMID- 16595626
TI  - Directed evolution to probe protein allostery and integrin I domains of 200,000
      fold higher affinity.
AB  - Understanding allostery may serve to both elucidate mechanisms of protein
      regulation and provide a basis for engineering active mutants. Herein we describe
      directed evolution applied to the integrin alpha(L) inserted domain for studying
      allostery by using a yeast surface display system. Many hot spots for activation
      are identified, and some single mutants exhibit remarkable increases of 10,000
      fold in affinity for a physiological ligand, intercellular adhesion molecule-1.
      The location of activating mutations traces out an allosteric interface in the
      interior of the inserted domain that connects the ligand binding site to the
      alpha7-helix, which communicates allostery to neighboring domains in intact
      integrins. The combination of two activating mutations (F265S/F292G) leads to an
      increase of 200,000-fold in affinity to intercellular adhesion molecule-1. The
      F265S/F292G mutant is potent in antagonizing lymphocyte function-associated
      antigen 1-dependent lymphocyte adhesion, aggregation, and transmigration.

PMID- 16595628
TI  - Cardiac-specific elevations in thyroid hormone enhance contractility and prevent
      pressure overload-induced cardiac dysfunction.
AB  - Thyroid hormone (TH) is critical for cardiac development and heart function. In
      heart disease, TH metabolism is abnormal, and many biochemical and functional
      alterations mirror hypothyroidism. Although TH therapy has been advocated for
      treating heart disease, a clear benefit of TH has yet to be established, possibly
      because of peripheral actions of TH. To assess the potential efficacy of TH in
      treating heart disease, type 2 deiodinase (D2), which converts the prohormone
      thyroxine to active triiodothyronine (T3), was expressed transiently in mouse
      hearts by using the tetracycline transactivator system. Increased cardiac D2
      activity led to elevated cardiac T3 levels and to enhanced myocardial
      contractility, accompanied by increased Ca(2+) transients and sarcoplasmic
      reticulum (SR) Ca(2+) uptake. These phenotypic changes were associated with up
      regulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) 2a expression
      as well as decreased Na(+)/Ca(2+) exchanger, beta-myosin heavy chain, and
      sarcolipin (SLN) expression. In pressure overload, targeted increases in D2
      activity could not block hypertrophy but could completely prevent impaired
      contractility and SR Ca(2+) cycling as well as altered expression patterns of
      SERCA2a, SLN, and other markers of pathological hypertrophy. Our results
      establish that elevated D2 activity in the heart increases T3 levels and enhances
      cardiac contractile function while preventing deterioration of cardiac function
      and altered gene expression after pressure overload.

PMID- 16595629
TI  - CeRh1 (rhr-1) is a dominant Rhesus gene essential for embryonic development and
      hypodermal function in Caenorhabditis elegans.
AB  - Rhesus (Rh) proteins share a conserved 12-transmembrane topology and specify a
      family of putative CO(2) channels found in diverse species from microbes to
      human, but their functional essentiality and physiological importance in
      metazoans is unknown. To address this key issue and analyze Rh-engaged
      physiologic processes, we sought to explore model organisms with fewer Rh genes
      yet are tractable to genetic manipulations. In this article, we describe the
      identification in nematodes of two Rh homologues that are highly conserved and
      similar to human Rh glycoproteins, and we focus on their characterization in
      Caenorhabditis elegans. RNA analysis revealed that CeRh1 is abundantly expressed
      in all developmental stages, with highest levels in adults, whereas CeRh2 shows a
      differential and much lower expression pattern. In transient expression in human
      cells, both CeRh1 and CeRh2-GFP fusion proteins were routed to the plasma
      membrane. Transgenic analysis with GFP or LacZ-fusion reporters showed that CeRh1
      is mainly expressed in hypodermal tissue, although it is also in other cell
      types. Mutagenesis analysis using deletion constructs mapped a minimal promoter
      region driving CeRh1 gene expression. Although CeRh2 was dispensable, RNA
      interference with CeRh1 caused a lethal phenotype mainly affecting late stages of
      C. elegans embryonic development, which could be rescued by the CbRh1 homologue
      from the worm Caenorhabditis briggsae. Taken together, our data provide direct
      evidence for the essentiality of the CeRh1 gene in C. elegans, establishing a
      useful animal model for investigating CO(2) channel function by cross-species
      complementation.

PMID- 16595630
TI  - Spectral statistics in natural scenes predict hue, saturation, and brightness.
AB  - The perceptual color qualities of hue, saturation, and brightness do not
      correspond in any simple way to the physical characteristics of retinal stimuli,
      a fact that poses a major obstacle for any explanation of color vision. Here we
      test the hypothesis that these basic color attributes are determined by the
      statistical covariations in the spectral stimuli that humans have always
      experienced in typical visual environments. Using a database of 1,600 natural
      images, we analyzed the joint probability distributions of the physical variables
      most relevant to each of these perceptual qualities. The cumulative density
      functions derived from these distributions predict the major colorimetric
      functions that have been reported in psychophysical experiments over the last
      century.

PMID- 16595631
TI  - Coordinated binding of NF-kappaB family members in the response of human cells to
      lipopolysaccharide.
AB  - The NF-kappaB family of transcription factors plays a critical role in numerous
      cellular processes, particularly the immune response. Our understanding of how
      the different NF-kappaB subunits act coordinately to regulate gene expression is
      based on a limited set of genes. We used genome-scale location analysis to
      identify targets of all five NF-kappaB proteins before and after stimulation of
      monocytic cells with bacterial lipopolysaccharide (LPS). In unstimulated cells,
      p50 and p52 bound to a large number of gene promoters that were also occupied by
      RNA polymerase II. After LPS stimulation, additional NF-kappaB subunits bound to
      these genes and to other genes. Genes that became bound by multiple NF-kappaB
      subunits were the most likely to show increases in RNA polymerase II occupancy
      and gene expression. This study identifies NF-kappaB target genes, reveals how
      the different NF-kappaB proteins coordinate their activity, and provides an
      initial map of the transcriptional regulatory network that underlies the host
      response to infection.

PMID- 16595632
TI  - A neurosphere-derived factor, cystatin C, supports differentiation of ES cells
      into neural stem cells.
AB  - Although embryonic stem (ES) cells are capable of unlimited proliferation and
      pluripotent differentiation, effective preparation of neural stem cells from ES
      cells are not achieved. Here, we have directly generated under the coculture with
      dissociated primary neurosphere cells in serum-free medium and the same effect
      was observed when ES cells were cultured with conditioned medium of primary
      neurosphere culture (CMPNC). ES-neural stem cells (NSCs) could proliferate for
      more than seven times and differentiate into neurons, astrocytes, and
      oligodendrocytes in vitro and in vivo. The responsible molecule in CMPNC was
      confirmed by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry, which turned out to be cystatin C. Purified cystatin C in place of
      the CMPNC could generate ES-NSCs efficiently with self-renewal and
      multidifferentiation potentials. These results reveal the validity of cystatin C
      for generating NSCs from ES cells.

PMID- 16595633
TI  - Synphilin-1A: an aggregation-prone isoform of synphilin-1 that causes neuronal
      death and is present in aggregates from alpha-synucleinopathy patients.
AB  - alpha-Synucleinopathies are a group of neurological disorders characterized by
      the presence of intracellular inclusion bodies containing alpha-synuclein. We
      previously demonstrated that synphilin-1 interacts with alpha-synuclein, implying
      a role in Parkinson's disease. We now report the identification and
      characterization of synphilin-1A, an isoform of synphilin-1, which has enhanced
      aggregatory properties and causes neurotoxicity. The two transcripts encoding
      synphilin-1A and synphilin-1 originate from the SNCAIP gene but differ in both
      their exon organization and initial reading frames used for translation.
      Synphilin-1A binds to alpha-synuclein and induces the formation of intracellular
      aggregates in human embryonic kidney 293 cells, primary neuronal cultures, and
      human dopaminergic cells. Overexpression of synphilin-1A in neurons results in
      striking cellular toxicity that is attenuated by the formation of synphilin-1A
      inclusions, which recruit alpha-synuclein. Synphilin-1A is present in Lewy bodies
      of patients with Parkinson's disease and Diffuse Lewy Body disease, and is
      observed in detergent-insoluble fractions of brain protein samples obtained from
      Diffuse Lewy Body disease patients. These findings suggest that synphilin-1A may
      contribute to neuronal degeneration in alpha-synucleinopathies and also provide
      important insights into the role of inclusion bodies in neurodegenerative
      disorders.

PMID- 16595634
TI  - Spinal cord endoplasmic reticulum stress associated with a microsomal
      accumulation of mutant superoxide dismutase-1 in an ALS model.
AB  - Mutation in superoxide dismutase-1 (SOD1), which is a cause of ALS, alters the
      folding patterns of this protein. Accumulation of misfolded mutant SOD1 might
      activate endoplasmic reticulum (ER) stress pathways. Here we show that transgenic
      mice expressing ALS-linked SOD1 mutants exhibit molecular alterations indicative
      of a recruitment of ER's signaling machinery. We demonstrate by biochemical and
      morphological methods that mutant SOD1 accumulates inside the ER, where it forms
      insoluble high molecular weight species and interacts with the ER chaperone
      immunoglobulin-binding protein. These alterations are age- and region-specific,
      because they develop over the course of the disease and occur in the affected
      spinal cord but not in the nonaffected cerebellum in transgenic mutant SOD1 mice.
      Our results suggest a toxic mechanism for mutant SOD1 by which this ubiquitously
      expressed pathogenic protein could affect motor neuron survival and contribute to
      the selective motor neuronal degeneration in ALS.

PMID- 16595635
TI  - The adaptor protein Nck interacts with Fas ligand: Guiding the death factor to
      the cytotoxic immunological synapse.
AB  - The Fas ligand (FasL) is a key death factor of cytotoxic T lymphocytes and
      natural killer cells. It is stored intracellularly as a transmembrane protein of
      secretory lysosomes. Upon activation, these vesicles are transported to the
      cytotoxic immunological synapse (IS), and FasL becomes exposed to the cell
      surface to trigger cell death through ligation of its receptor Fas (CD95) on the
      target cell. We propose that the FasL-associated adaptor protein Nck is involved
      in the actin-dependent transport of FasL-bearing secretory lysosomes to the IS.
      Nck binds to the proline-rich portion of FasL and alters its subcellular
      distribution when coexpressed in 293T cells. In T lymphocytes, endogenous Nck
      partially colocalizes with lysosome-associated FasL. When T cell clones or lines
      are exposed to target cells, both proteins and other components of secretory
      lysosomes (i.e., granzyme B or cathepsin D) are transported to the cell-cell
      interface. The present data suggest that T cell receptor engagement provokes a
      rapid, tyrosine kinase- and actin-dependent transport of Nck-associated FasL
      carrying lysosomes to the contact area. Our observations support the previous
      notion that the unique cytoplasmic tail of FasL is crucial for its directed
      transport to the cell surface and into the assembling cytotoxic IS.

PMID- 16595637
TI  - Antiviral options for the treatment of chronic hepatitis B.
AB  - Hepatitis B virus (HBV) is an important cause of end-stage liver disease and
      hepatocellular carcinoma. Effective treatment can delay or prevent these
      outcomes. The decision to treat is based on the activity of liver disease and HBV
      replication status, and the likelihood of a long-term benefit. Approved therapies
      include standard and pegylated interferon-alfa and nucleoside analogues:
      lamivudine, adefovir and entecavir. Current therapies do not eradicate HBV so
      long-term treatment is usually required. Development of drug resistance is a
      major concern with long-term treatment. Even with successful therapy, patients
      remain at risk for reactivation of viral replication and require lifelong
      monitoring.

PMID- 16595639
TI  - In vitro activity of iron-binding compounds against Senegalese isolates of
      Plasmodium falciparum.
AB  - OBJECTIVES: The in vitro activities of FR160, a synthetic catecholate
      siderophore, and two iron-binding agents, desferrioxamine and doxycycline, were
      evaluated against Plasmodium falciparum isolates. Correlations between these
      compounds and standard antimalarial drugs (chloroquine, quinine, amodiaquine,
      pyronaridine, artemether, artesunate, atovaquone, cycloguanil and pyrimethamine)
      were assessed to determine any degree of cross-resistance. METHODS: Between
      October 1997 and February 1998, and September and November 1998, 189 P.
      falciparum isolates were obtained in Dielmo and Ndiop (Dakar). Their
      susceptibilities were assessed using an isotopic, microwell format, drug
      susceptibility test. RESULTS: The 137 inhibitory concentrations (IC(50)) values
      of FR160 ranged from 0.1 to 10 microM and the geometric mean IC(50) was 1.48
      microM (95% CI = 1.29-1.68 microM). The geometric mean IC(50) of doxycycline for
      121 isolates was 18.9 microM (95% CI = 16.8-21.3 microM) and that of
      desferrioxamine for 73 isolates was 20.7 microM (95% CI = 17.3-24.8 microM).
      FR160 was significantly less active against the chloroquine-resistant isolates (P
      < 0.0001). The mean IC(50)s of doxycycline were significantly higher for the
      chloroquine-susceptible isolates than for the resistant parasites (P = 0.0447).
      There was a weak correlation between the responses to FR160, desferrioxamine or
      doxycycline and those to the other antimalarial compounds (r(2) < 0.22).
      CONCLUSIONS: The activities of FR160 and desferrioxamine, determined for P.
      falciparum clones, were confirmed against 137 isolates. The coefficients of
      determination between the responses to FR160, doxycycline or desferrioxamine and
      those to all the antimalarial drugs tested are too weak to suggest cross
      resistance. FR160 could be a rationale partner to use in combination with
      doxycycline.

PMID- 16595638
TI  - Effect of MUC7 peptides on the growth of bacteria and on Streptococcus mutans
      biofilm.
AB  - OBJECTIVES: To investigate the susceptibility of selected bacteria as well as
      Streptococcus mutans biofilm to MUC7 peptides and compare the activities with
      those of other known antimicrobial peptides. METHODS: MIC and MBC of peptides for
      S. mutans, Escherichia coli, Streptococcus gordonii, Actinobacillus
      actinomycetemcomitans, Porphyromonas gingivalis and Pseudomonas aeruginosa were
      determined using the microdilution method. For S. mutans, the effects of the
      peptides on the kinetics of growth inhibition, time-killing, and on biofilm
      formation and reduction were also examined. For biofilm studies, polystyrene
      microtitre plates, Calgary Biofilm Device (CBD) and hydroxylapatite (HA) discs,
      along with Crystal Violet and Alamar Blue dyes, and/or EM observations, were
      employed. RESULTS: S. mutans was the most susceptible to all peptides tested
      (MICs of 9.4-25.0 microM), compared with the other species (MICs of 3.1->100
      microM). MUC7 peptides (except MUC7-12-mer-L4) exerted 2-fold higher activity
      against S. mutans than Hsn5-12-mer and magainin-II, and faster killing of S.
      mutans than Hsn5-12-mer. The MUC7 peptides also had an effect on S. mutans
      biofilm. On the polystyrene plates, they suppressed the biofilm formation, with
      MBIC(50) of 6.25-12.5 microM, and reduced the 1 day developed biofilm in a batch
      culture, with MBRC(50) of 25-50 microM. On the CBD pegs, the viabilities of the
      biofilm were suppressed by >95% in the presence of MUC7 peptides at 4x MIC (50
      microM). One day developed biofilm viabilities were inhibited by 49-75%. On HA,
      the formation of biofilm (as observed by EM) was also considerably reduced.
      CONCLUSIONS: MUC7 peptides present somewhat preferential antimicrobial activity
      against S. mutans. They also have an effect on in vitro formation and reduction
      of the preformed S. mutans biofilm.

PMID- 16595640
TI  - Klebsiella pneumoniae strains carrying the chromosomal SHV-11 beta-lactamase gene
      produce the plasmid-mediated SHV-12 extended-spectrum beta-lactamase more
      frequently than those carrying the chromosomal SHV-1 beta-lactamase gene.

PMID- 16595641
TI  - The use of pharmacokinetically guided indinavir dose reductions in the management
      of indinavir-associated renal toxicity.
AB  - OBJECTIVES: Indinavir is associated with nephrotoxicity. Therapeutic drug
      monitoring of indinavir improves clinical outcome, but there is little data
      regarding therapeutic drug monitoring for patients with established indinavir
      associated renal impairment. We prospectively studied the use of therapeutic drug
      monitoring in patients with virological success but established nephrotoxicity on
      an indinavir-containing regimen. METHODS: We measured indinavir C(trough)/C(2h),
      serum creatinine, pyuria, blood pressure (BP), weight and HIV RNA. The major
      endpoint of interest was the number of patients achieving a normal creatinine
      level 20 weeks following final indinavir dose adjustment. Primary analysis was by
      intention to treat (ITT). RESULTS: A total of 35 patients were enrolled; mean
      (SD) age 40.3 (5.8) years; mean (SD) BMI 21.5 (2.8) kg/m(2). At baseline 6/35
      (17%) had a serum creatinine concentration within normal limits, but were offered
      enrolment because of previous nephrotoxicity (nephrolithiasis and/or abnormal
      serum creatinine), and a screening pharmacokinetic profile associated with
      increased nephrotoxicity risk. By ITT analysis 11/35 (31%) had normal creatinine
      at study end (P = 0.18). Of the 29 patients with abnormal creatinine at baseline,
      7/29 (24.1%) had normal creatinine at study end (P = 0.016). Patients had a
      median (IQR) indinavir per dose adjustment over the study of 400 (400-800) mg. We
      observed improvements in estimated creatinine clearance, pyuria, resting BP and
      indinavir pharmacokinetic profile. HIV RNA control was maintained with continued
      immune recovery despite lower indinavir doses. CONCLUSIONS: Patients experiencing
      nephrotoxicity on an indinavir-containing regimen were safely maintained on
      indinavir by means of therapeutic drug monitoring. Parameters of renal function
      improved but did not return to baseline values, at least in the short-term.

PMID- 16595642
TI  - Treatment outcomes in patients receiving conventional amphotericin B therapy: a
      prospective multicentre study in Taiwan.
AB  - OBJECTIVES: To evaluate treatment outcomes and healthcare resource use with
      conventional amphotericin B therapy for invasive fungal infections (IFIs).
      PATIENTS AND METHODS: A prospective observational study in hospitalized adult
      patients receiving amphotericin B treatment was undertaken at four hospitals in
      Taiwan. Patients were observed from the start of therapy to hospital discharge.
      RESULTS: A total of 108 patients (October 2000 to April 2002) were included in
      the study. Proven or probable IFIs as defined by the EORTC/MSG criteria were the
      reasons for the initiation of amphotericin B in 35.2% of the sample. A total of
      24.1% patients developed nephrotoxicity (NT) (defined as a 50% increase in the
      baseline serum creatinine and achieving a peak of at least 2.0 mg/dL). Treatment
      of proven/probable IFIs [odds ratio (OR) = 4.16, 95% confidence interval (CI) =
      1.61-10.75] was a significant predictor of the development of NT. The in-hospital
      mortality rate was 38.0%. Proven/probable IFIs (OR = 6.93, 95% CI = 2.62-18.29)
      and the development of NT (OR = 3.68, 95% CI = 1.22-11.04) were independent
      predictors of in-hospital mortality. For patients alive at discharge, those with
      NT had a trend of longer hospital stay compared with patients who had not
      developed NT (mean, 49.3 +/- 18.2 versus 29.3 +/- 22.3 days, P = 0.069). For
      patients who died, those who had developed NT died sooner (15.5 +/- 16.7 versus
      33. 8 +/- 26.9 days, P = 0.0004). CONCLUSIONS: NT was associated with accelerated
      mortality and increased hospital stay for patients who survived. Using
      amphotericin B carefully or the use of antifungal agents with less potential for
      NT might improve patient outcomes.

PMID- 16595643
TI  - Synthesis and antileprosy activity of some dialkyldithiocarbamates.
AB  - OBJECTIVES: To investigate the antileprosy potential of a set of original
      compounds with antimycobacterial activity. METHODS: We developed a facile
      synthesis of 2-chloro-3-cyano-5-nitropyridine and synthesized a series of 3-cyano
      2-dialkyldithiocarbamoyl-5-nitropyridine derivatives. In vivo therapeutic
      efficacy against Mycobacterium leprae was assessed in the infected mouse footpad
      model. RESULTS: The compounds were active in vitro against Mycobacterium
      smegmatis, Mycobacterium aurum, Mycobacterium vaccae and Mycobacterium fortuitum,
      with MICs generally in the range of 0.4-6.25 mg/L. Reduction of the bacterial
      load in vivo in the mouse footpad and toxic side effects were dependent on the
      individual structure of the compounds and on the doses applied. Compounds 2a, 3a
      and 3b reduced the number of M. leprae by two orders of magnitude, comparable to
      the effect of dapsone. Co-administration of compounds 2a and 3a with dapsone
      synergistically enhanced the activity. In addition, these compounds were well
      tolerated over the treatment period of 7.5 months. CONCLUSIONS: Individual
      synthetic dithiocarbamate derivatives have promising antileprosy activity.

PMID- 16595644
TI  - Incidence of symptomatic vitamin D deficiency.
AB  - A survey of West Midlands paediatricians in 2001 identified 24 cases of
      symptomatic vitamin D deficiency in children less than 5 years of age. The
      overall incidence was 7.5 per 100,000 children per year with notable differences
      in incidence per ethnic group.

PMID- 16595645
TI  - Improvement in screening performance and diagnosis of congenital hypothyroidism
      in Scotland 1979-2003.
AB  - AIM: To assess the Scottish newborn screening programme for congenital
      hypothyroidism from 1994 to 2003 (period 2) for performance and compare with an
      initial audit covering 1979 to 1993 (period 1). DESIGN: Performance data-age at
      blood spot sampling, notification by screening laboratory, start of treatment,
      and the prevalence of late testing, notification or treatment-were compared,
      together with the incidence of congenital hypothyroidism. RESULTS: Comparing data
      for period 2 with period 1, the mean annual incidence of true congenital
      hypothyroidism was 1:3655 live births v 1:4363. Median age for Guthrie sampling
      (all referrals) was 6 v 7 days (p<0.0001). Late sampling (>10 days) had fallen
      from 10.7% to 7%. For infants requiring repeat sampling before notification, the
      median (range) interval between initial and final repeat samples was 11 (1 to 52)
      compared with 14 (3 to 73) days. Median age at notification for true congenital
      hypothyroidism was 10 v 12 days (p <0.0001). Late notification (>15 days) was
      justifiable (mild TSH elevation) in 10 of 13 patients in period 2. Median age at
      start of treatment for true congenital hypothyroidism had improved to 11 days
      from 13.5 days. For true congenital hypothyroidism, late treatment (>16 days)
      occurred in 7% of patients compared with 19% (p<0.0001). CONCLUSIONS: There has
      been an improvement in performance measures for the congenital hypothyroidism
      screening programme in Scotland. However, late sampling, occurring primarily in
      inpatients and which is never justified, remains a problem, while the interval
      between initial and recall sampling is a further source of delay.

PMID- 16595646
TI  - The significance of cutaneous spider naevi in children.
AB  - BACKGROUND: Cutaneous spider naevi are commonly considered to be a clinical sign
      of chronic liver disease. Little is known about their occurrence in children.
      AIM: To evaluate the occurrence of spider naevi in children with and without
      liver disease. METHODS: The presence of spider naevi was investigated in 460
      children, 34 of whom had chronic liver disease. RESULTS: Of children without
      liver involvement, 38% had at least one spider naevus. The prevalence of spider
      naevi increased with age. Of control patients aged 5 to 15 years, 2.5% had more
      than five spiders present. Although eight of 10 children with cirrhosis had at
      least one spider naevus, only four of 34 children with chronic liver disease had
      five or more spiders present. Most spiders were on the hands and very few were >5
      mm in size. CONCLUSIONS: Children with liver disease rarely have large numbers of
      spider naevi. Although the finding of five or more spider naevi is more common in
      liver disease, many normal children also have one or more of these lesions.

PMID- 16595647
TI  - Clinical decision rules to distinguish between bacterial and aseptic meningitis.
AB  - BACKGROUND: Clinical decision rules have been derived to distinguish between
      bacterial and aseptic meningitis in the emergency room to avoid unnecessary
      antibiotic treatments and hospitalisations. AIMS: To evaluate the reproducibility
      and to compare the diagnostic performance of five clinical decision rules.
      METHODS: All children hospitalised for bacterial meningitis between 1995 and 2004
      or aseptic meningitis between 2000 and 2004 have been included in a retrospective
      cohort study. Sensitivity and specificity were calculated by applying each rule
      to the patients. The best rule was a priori defined as the one yielding 100%
      sensitivity for bacterial meningitis, the highest specificity, and the greatest
      simplicity for a bedside application. RESULTS: Among the 166 patients included,
      20 had bacterial meningitis and 146 had aseptic meningitis. Although three rules
      achieved 100% sensitivity (95% CI 84-100), one had a significantly lower
      specificity (13%, 95% CI 8-19) than those of the other two rules (57%, 95% CI 48
      65; and 66%, 95% CI 57-73), which were not statistically different. The ease of
      manual computation of the rule developed by Nigrovic et al (a simple list of five
      items: seizure, blood neutrophil count, cerebrospinal fluid (CSF) Gram stain, CSF
      protein, CSF neutrophil count) was higher than the one developed by Bonsu and
      Harper. CONCLUSION: On our population, the rule derived by Nigrovic et al had the
      best balance between accuracy and simplicity of manual computation and could help
      to avoid two thirds of unnecessary antibiotic treatments and hospitalisations.

PMID- 16595649
TI  - Distinct subcellular localization for constitutive and agonist-modulated
      palmitoylation of the human delta opioid receptor.
AB  - Protein palmitoylation is a reversible lipid modification that plays important
      roles for many proteins involved in signal transduction, but relatively little is
      known about the regulation of this modification and the cellular location where
      it occurs. We demonstrate that the human delta opioid receptor is palmitoylated
      at two distinct cellular locations in human embryonic kidney 293 cells and
      undergoes dynamic regulation at one of these sites. Although palmitoylation could
      be readily observed for the mature receptor (Mr 55,000), [3H]palmitate
      incorporation into the receptor precursor (Mr 45,000) could be detected only
      following transport blockade with brefeldin A, nocodazole, and monensin,
      indicating that the modification occurs initially during or shortly after export
      from the endoplasmic reticulum. Blocking of palmitoylation with 2-bromopalmitate
      inhibited receptor cell surface expression, indicating that it is needed for
      efficient intracellular transport. However, cell surface biotinylation
      experiments showed that receptors can also be palmitoylated once they have
      reached the plasma membrane. At this location, palmitoylation is regulated in a
      receptor activation-dependent manner, as was indicated by the opioid agonist
      promoted increase in the turnover of receptor-bound palmitate. This agonist
      mediated effect did not require receptor-G protein coupling and occurred at the
      cell surface without the need for internalization or recycling. The activation
      dependent modulation of receptor palmitoylation may thus contribute to the
      regulation of receptor function at the plasma membrane.

PMID- 16595648
TI  - PFAPA syndrome: new clinical aspects disclosed.
AB  - BACKGROUND: The recently described PFAPA (Periodic Fever, Aphthous stomatitis,
      Pharyngitis and Adenitis) syndrome is characterised by periodic fever, aphthous
      stomatitis, pharyngitis and adenitis. However, there are currently relatively few
      data on the natural history of this syndrome. OBJECTIVE: To describe the
      presentation, clinical course, doctors' awareness, therapeutic response and long
      term follow-up of children with PFAPA syndrome. METHODS: Children with PFAPA
      syndrome referred over a 5-year period (from January 1999 to January 2004) were
      enrolled in the study. Data were gathered from medical records, parents'
      interviews, physical examination and telephone calls. RESULTS: 54 patients with
      PFAPA syndrome were evaluated. Our patients had a higher rate of abdominal pain
      (65%) and a lower rate of aphthous stomatitis (39%) than those in previous
      reports. Four different patterns of disease evolution were identified, including
      the relatively common (n = 14, 26%) and newly described course of alternating
      remissions and relapses. The remissions lasted 8.5 months on average (range 4-36
      months). Diagnosis was established by primary paediatricians in 30 of 54 (56%)
      patients. However, a substantial delay in diagnosis was apparent (mean 15
      months). Episodes were curtailed by a much lower dose of prednisone or equivalent
      corticosteroid (mean 0.6 mg/kg/day, range 0.15-1.5 mg/kg/day) than reported
      previously. Tonsillectomy was successful in the prevention of recurrence of
      further episodes in all six patients who underwent the procedure. CONCLUSIONS: We
      describe several new characteristics of PFAPA syndrome in children, contributing
      to our knowledge of this relatively unrecognised but troublesome syndrome. Early
      diagnosis and appropriate treatment can markedly improve the quality of life of
      both patients and families.

PMID- 16595650
TI  - Messenger-specific role for nicotinic acid adenine dinucleotide phosphate in
      neuronal differentiation.
AB  - Cells possess several Ca2+-mobilizing messengers, which couple stimulation at the
      cell surface by a multitude of extracellular cues to the regulation of
      intracellular Ca2+-sensitive targets. Recent studies suggest that agonists
      differentially select from this molecular palette to generate their
      characteristic Ca2+ signals but it is still unclear whether different messengers
      mediate different functions or whether they act in a redundant fashion. In this
      study, we compared the effects of nicotinic acid adenine dinucleotide phosphate
      (NAADP), a novel Ca2+-mobilizing messenger, with that of the prototypical
      messenger inositol trisphosphate on cytosolic Ca2+ levels and differentiation
      status of PC12 cells. We demonstrate that liposomal delivery of NAADP mediated
      release of Ca2+ from acidic Ca2+ stores and that this stimulus was sufficient to
      drive differentiation of the cells to a neuronal-like phenotype. In sharp
      contrast, cell fate was unaffected by more transient Ca2+ signals generated by
      inositol trisphosphate-evoked release of endoplasmic reticulum Ca2+ stores. Our
      data establish for the first time (i) the presence of novel NAADP-sensitive Ca2+
      stores in PC12 cells, (ii) a role for NAADP in differentiation, and (iii) that
      Ca2+-dependent function can be messenger-specific. Thus, differential recruitment
      of intracellular Ca2+-mobilizing messengers and their target Ca2+ stores may
      represent a robust means of maintaining stimulus fidelity in the control of Ca2+
      dependent cell function.

PMID- 16595651
TI  - Transcription factors, cAMP-responsive element modulator (CREM) and Tisp40, act
      in concert in postmeiotic transcriptional regulation.
AB  - We previously isolated 80 TISP (transcript induced in spermiogenesis) genes whose
      transcription is dramatically induced during spermiogenesis. Our analysis here of
      the expression of these genes in the testis of the cAMP-responsive element
      modulator (CREM)-null mouse revealed that 54 TISP genes are under the
      transcriptional regulation of CREM. One CREM-regulated gene is TISP40, which
      encodes a basic leucine zipper (bZip)-type transcription factor bearing a
      transmembrane domain that generates the two proteins Tisp40alpha and Tisp40beta.
      Both of these proteins function by binding to UPRE (unfolded protein-response
      element) but do not recognize CRE motifs. We show here that Tisp40alpha mRNA is
      generated under the direct transcriptional regulation of CREM. CREMtau and Tisp40
      form a heterodimer, which functions through CRE but not through UPRE.
      Furthermore, binding ability of CREM to CRE is dramatically up-regulated by
      forming a heterodimer with Tisp40alphaDeltaTM, a truncated form of Tisp40alpha
      that lacks the transmembrane domain. We confirmed that Tisp40 and CREM actually
      bind to the Tisp40 promoter in vivo by chromatin immunoprecipitation assay.
      Finally, we demonstrate that the Tisp40DeltaTM-CREMtau heterodimer acts as a
      recruiter of HIRA, a histone chaperone, to CRE. Taken together, we propose that
      Tisp40 is an important transcriptional regulator during spermiogenesis.

PMID- 16595652
TI  - Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of
      synaptotagmin 1.
AB  - Ca2+-dependent phospholipid binding to the C2A and C2B domains of synaptotagmin 1
      is thought to trigger fast neurotransmitter release, but only Ca2+ binding to the
      C2B domain is essential for release. To investigate the underlying mechanism, we
      have compared the role of basic residues in Ca2+/phospholipid binding and in
      release. Mutations in a polybasic sequence on the side of the C2B domain beta
      sandwich or in a basic residue in a top Ca2+-binding loop of the C2A domain
      (R233) cause comparable decreases in the apparent Ca2+ affinity of synaptotagmin
      1 and the Ca2+ sensitivity of release, whereas mutation of the residue homologous
      to Arg233 in the C2B domain (Lys366) has no effect. Phosphatidylinositol
      polyphosphates co-activate Ca2+-dependent and -independent phospholipid binding
      to synaptotagmin 1, but the effects of these mutations on release only correlate
      with their effects on the Ca2+-dependent component. These results reveal clear
      distinctions in the Ca2+-dependent phospholipid binding modes of the
      synaptotagmin 1 C2 domains that may underlie their functional asymmetry and
      suggest that phosphatidylinositol polyphosphates may serve as physiological
      modulators of Ca2+ affinity of synaptotagmin 1 in vivo.

PMID- 16595654
TI  - Phospholipase D couples survival and migration signals in stress response of
      human cancer cells.
AB  - MDA-MB-231 human breast cancer cells belong to a highly invasive metastatic cell
      line that depends on phospholipase D (PLD) activity for survival when deprived of
      serum growth factors. In response to the stress of serum withdrawal, there is a
      rapid and dramatic increase in PLD activity. Concomitant with increased PLD
      activity, there was an increase in the ability of MDA-MB-231 cells to both
      migrate and invade Matrigel. The ability of MDA-MB-231 cells to both migrate and
      invade Matrigel was dependent on both PLD and mTOR, a downstream target of PLD
      signals. Serum withdrawal also led to a PLD-dependent increase in the expression
      of the stress factor, hypoxia-inducible factor-1alpha. These data reveal that PLD
      survival signals not only prevent apoptosis but also stimulate cell migration and
      invasion, linking the ability to suppress apoptosis with the ability to
      metastasize.

PMID- 16595653
TI  - Pseudomonas aeruginosa porin OprF exists in two different conformations.
AB  - The major nonspecific porin of Pseudomonas aeruginosa, OprF, produces a large
      channel yet allows only a slow diffusion of various solutes. Here we provide an
      explanation of this apparent paradox. We first show, by introduction of tobacco
      etch virus protease cleavage site in the middle of OprF protein, that most of
      OprF population folds as a two-domain protein with an N-terminal beta-barrel
      domain and a C-terminal periplasmic domain rich in alpha-helices. However,
      sedimentation of unilamellar proteoliposomes through an iso-osmotic gradient
      showed that only about 5% of the OprF population produced open channels. Gel
      filtration showed that the open channel conformers tended to occur in oligomeric
      associations. Because the open channel conformer is likely to fold as a single
      domain protein with a large beta-barrel, we reasoned that residues near the C
      terminus may be exposed on cell surface in this conformer. Introduction of a
      cysteine residue at position 312 produced a functional mutant protein. By using
      bulky biotinylation reagents on intact cells, we showed that this cysteine
      residue was not exposed on cell surface in most of the OprF population. However,
      the minority OprF population that was biotinylated in such experiments was
      enriched for the conformer with pore-forming activity and had a 10-fold higher
      pore-forming specific activity than the bulk OprF population. Finally trypsin
      treatment, which preferentially cleaves the C-terminal domain of the two-domain
      conformer, did not affect the pore-forming activity of OprF nor did it digest the
      minority conformer whose residue 312 is exposed on cell surface.

PMID- 16595655
TI  - Evolutionarily conserved allosteric network in the Cys loop family of ligand
      gated ion channels revealed by statistical covariance analyses.
AB  - The Cys loop family of ligand-gated ion channels mediate fast synaptic
      transmission for communication between neurons. They are allosteric proteins, in
      which binding of a neurotransmitter to its binding site in the extracellular
      amino-terminal domain triggers structural changes in distant transmembrane
      domains to open a channel for ion flow. Although the locations of binding site
      and channel gating machinery are well defined, the structural basis of the
      activation pathway coupling binding and channel opening remains to be determined.
      In this paper, by analyzing amino acid covariance in a multiple sequence
      alignment, we have identified an energetically interconnected network in the Cys
      loop family of ligand-gated ion channels. Statistical coupling and correlated
      mutational analyses along with clustering revealed a highly coupled cluster.
      Mapping the positions in the cluster onto a three-dimensional structural model
      demonstrated that these highly coupled positions form an interconnected network
      linking experimentally identified binding domains through the coupling region to
      the gating machinery. In addition, these highly coupled positions are also
      condensed in the transmembrane domains, which are a recent focus for the sites of
      action of many allosteric modulators. Thus, our results revealed a genetically
      interconnected network that potentially plays an important role in the allosteric
      activation and modulation of the Cys loop family of ligand-gated ion channels.

PMID- 16595656
TI  - Identification of the mitochondrial targeting signal of the human equilibrative
      nucleoside transporter 1 (hENT1): implications for interspecies differences in
      mitochondrial toxicity of fialuridine.
AB  - We have previously shown that the human equilibrative nucleoside transporter 1
      (hENT1) is expressed and functional in the mitochondrial membrane and that this
      expression enhances the mitochondrial toxicity of the nucleoside drug,
      fialuridine (FIAU) (Lai, Y., Tse, C. M., and Unadkat, J. D. (2004) J. Biol. Chem.
      279, 4490-4497). Here we report on identification of the mitochondrial targeting
      sequence of hENT1. Using confocal microscopy and different truncated and point
      mutants of hENT1-YFP (yellow fluorescent protein) expressed in Madin-Darby canine
      kidney cells, we identified amino acid residues Pro(71),Glu(72), and Asn(74) (the
      PEXN motif) of hENT1 as important in mitochondrial targeting of hENT1.
      Identification of this mitochondrial targeting sequence provides a possible
      explanation for the dramatic difference in mitochondrial toxicity of FIAU between
      humans and rodents. Although the mouse ENT1 (mENT1), expressed in Madin-Darby
      canine kidney cells, can transport FIAU, confocal microscopy showed that mENT1
      GFP (green fluorescent protein) was not localized to the mitochondria. Consistent
      with this observation, mitochondria isolated from mouse livers did not transport
      FIAU. Sequence alignment of hENT1, mENT1, and rat ENT1 (rENT1) showed that the
      PEXN motif of hENT1 was substituted with a PAXS motif in both mENT1 and rENT1.
      Substitution of PAXS in mENT1 with PEXN (to create mENT1-PEXN-GFP) and of PEXN in
      hENT1 with PAXS (to create hENT1-PAXS-YFP) resulted in partial mitochondrial
      localization of mENT1-PEXN-GFP and loss of mitochondrial localization of hENT1
      PAXS-YFP. This is the first time that the mitochondrial targeting signal of hENT1
      has been identified. Our data suggest that the lack of mitochondrial toxicity of
      FIAU in mice is due to the lack of mENT1 targeting to and expression in the
      mitochondria.

PMID- 16595657
TI  - A second thylakoid membrane-localized Alb3/OxaI/YidC homologue is involved in
      proper chloroplast biogenesis in Arabidopsis thaliana.
AB  - The integral membrane proteins Alb3, OxaI, and YidC belong to an evolutionary
      conserved protein family mediating protein insertion into the thylakoid membrane
      of chloroplasts, the inner membrane of mitochondria, and bacteria, respectively.
      Whereas OxaI and YidC are involved in the insertion of a wide range of membrane
      proteins, the function of Alb3 seems to be limited to the insertion of a subset
      of the light-harvesting chlorophyll-binding proteins. In this study, we
      identified a second chloroplast homologue of the Alb3/OxaI/YidC family, named
      Alb4. Alb4 is almost identical to the Alb3/OxaI/YidC domain of the previously
      described 110-kDa inner envelope protein Artemis. We show that Alb4 is expressed
      as a separate 55-kDa protein and that Artemis was identified mistakenly. Alb4 is
      located in the thylakoid membrane of Arabidopsis thaliana chloroplasts. Analysis
      of an Arabidopsis mutant (Salk_136199) and RNA interference lines with a reduced
      level of Alb4 revealed chloroplasts with an altered ultrastructure. Mutant
      plastids are larger and more spherical in appearance, and the grana stacks within
      the mutant lines are less appressed than in the wild-type chloroplasts. These
      data indicate that Alb4 is required for proper chloroplast biogenesis.

PMID- 16595658
TI  - Domain requirement for the membrane trafficking and targeting of syntaxin 1A.
AB  - Syntaxin plays a key role in intracellular membrane fusion in eukaryotic cells.
      The function of syntaxin relies on its proper trafficking to and targeting at the
      target membrane. The mechanisms underlying the trafficking and targeting of
      syntaxin to its physiological sites remain poorly understood. Here we have
      analyzed the trafficking of syntaxin 1A in INS-1 and CHO cells. We have
      identified the transmembrane domain together with several flanking positive
      charged amino acids as the minimal domain required for the membrane delivery.
      Interestingly, we found that SNARE motif-exposed syntaxin 1A mutants were
      retained in endoplasmic reticulum (ER) and failed to transport to the cell
      surface in the absence of SNAP-25, suggesting that the exposure of the SNARE
      motif causes ER retention and complexation with SNAP-25 helps the ER escape.
      Finally, our data propose two key roles for the H(abc) domain: to protect
      nonspecific interaction by masking the SNARE motif and to participate in the
      clustering of syntaxin 1A to the fusion sites in the plasma membrane.

PMID- 16595659
TI  - Modulation of Kv3.1b potassium channel phosphorylation in auditory neurons by
      conventional and novel protein kinase C isozymes.
AB  - In fast-spiking neurons such as those in the medial nucleus of the trapezoid body
      (MNTB) in the auditory brainstem, Kv3.1 potassium channels are required for high
      frequency firing. The Kv3.1b splice variant of this channel predominates in the
      mature nervous system and is a substrate for phosphorylation by protein kinase C
      (PKC) at Ser-503. In resting neurons, basal phosphorylation at this site
      decreases Kv3.1 current, reducing neuronal ability to follow high frequency
      stimulation. We used a phospho-specific antibody to determine which PKC isozymes
      control serine 503 phosphorylation in Kv3.1b-tranfected cells and in auditory
      neurons in brainstem slices. By using isozyme-specific inhibitors, we found that
      the novel PKC-delta isozyme, together with the novel PKC-epsilon and conventional
      PKCs, contributed to the basal phosphorylation of Kv3.1b in MNTB neurons. In
      contrast, only PKC-epsilon and conventional PKCs mediate increases in
      phosphorylation produced by pharmacological activation of PKC in MNTB neurons or
      by metabotropic glutamate receptor activation in Kv3.1/mGluR1-cotransfected
      cells. We also measured the time course of dephosphorylation and recovery of
      basal phosphorylation of Kv3.1b following brief high frequency electrical
      stimulation of the trapezoid body, and we determined that the recovery process is
      mediated by both novel PKC-delta and PKC-epsilon isozymes and by conventional
      PKCs. The association between Kv3.1b and PKC isozymes was confirmed by reciprocal
      coimmunoprecipitation of Kv3.1b with multiple PKC isozymes. Our results suggest
      that the Kv3.1b channel is regulated by both conventional and novel PKC isozymes
      and that novel PKC-delta contributes specifically to the maintenance of basal
      phosphorylation in auditory neurons.

PMID- 16595661
TI  - Heme oxygenase-1 enhances renal mitochondrial transport carriers and cytochrome C
      oxidase activity in experimental diabetes.
AB  - Up-regulation of heme oxygenase (HO-1) by either cobalt protoporphyrin (CoPP) or
      human gene transfer improves vascular and renal function by several mechanisms,
      including increases in antioxidant levels and decreases in reactive oxygen
      species (ROS) in vascular and renal tissue. The purpose of the present study was
      to determine the effect of HO-1 overexpression on mitochondrial transporters,
      cytochrome c oxidase, and anti-apoptotic proteins in diabetic rats
      (streptozotocin, (STZ)-induced type 1 diabetes). Renal mitochondrial carnitine,
      deoxynucleotide, and ADP/ATP carriers were significantly reduced in diabetic
      compared with nondiabetic rats (p < 0.05). The citrate carrier was not
      significantly decreased in diabetic tissue. CoPP administration produced a robust
      increase in carnitine, citrate, deoxynucleotide, dicarboxylate, and ADP/ATP
      carriers and no significant change in oxoglutarate and aspartate/glutamate
      carriers. The increase in mitochondrial carriers (MCs) was associated with a
      significant increase in cytochrome c oxidase activity. The administration of tin
      mesoporphyrin (SnMP), an inhibitor of HO-1 activity, prevented the restoration of
      MCs in diabetic rats. Human HO-1 cDNA transfer into diabetic rats increased both
      HO-1 protein and activity, and restored mitochondrial ADP/ATP and deoxynucleotide
      carriers. The increase in HO-1 by CoPP administration was associated with a
      significant increase in the phosphorylation of AKT and levels of BcL-XL proteins.
      These observations in experimental diabetes suggest that the cytoprotective
      mechanism of HO-1 against oxidative stress involves an increase in the levels of
      MCs and anti-apoptotic proteins as well as in cytochrome c oxidase activity.

PMID- 16595660
TI  - Sp1 is up-regulated in cellular and transgenic models of Huntington disease, and
      its reduction is neuroprotective.
AB  - Interactions between mutant huntingtin (Htt) and a variety of transcription
      factors including specificity proteins (Sp) have been suggested as a central
      mechanism in Huntington disease (HD). However, the transcriptional activity
      induced by Htt in neurons that triggers neuronal death has yet to be fully
      elucidated. In the current study, we characterized the relationship of Sp1 to Htt
      protein aggregation and neuronal cell death. We found increased levels of Sp1 in
      neuronal-like PC12 cells expressing mutant Htt, primary striatal neurons, and
      brain tissue of HD transgenic mice. Sp1 levels were also elevated when 3
      nitropropionate (3-NP) was used to induce cell death in PC12 cells. To assess the
      effects of knocking down Sp1 in HD pathology, we used Sp1 siRNA, a heterozygous
      Sp1 knock-out mouse, and mithramycin A, a DNA-intercalating agent that inhibits
      Sp1 function. The three approaches consistently yielded reduced levels of Sp1
      which ameliorated toxicity caused by either mutant Htt or 3-NP. In addition, when
      HD mice were crossed with Sp1 heterozygous knock-out mice, the resulting
      offspring did not experience the loss of dopamine D2 receptor mRNA characteristic
      of HD mice, and survived longer than their HD counterparts. Our data suggest that
      enhancement of transcription factor Sp1 contributes to the pathology of HD and
      demonstrates that its suppression is beneficial.

PMID- 16595662
TI  - The MurE synthetase from Thermotoga maritima is endowed with an unusual D-lysine
      adding activity.
AB  - The peptidoglycan of Thermotoga maritima, an extremely thermophilic eubacterium,
      was shown to contain no diaminopimelic acid and approximate amounts of both
      enantiomers of lysine (Huber, R., Langworthy, T. A., Konig, H., Thomm, M., Woese,
      C. R., Sleytr, U. B., and Stetter, K. O. (1986) Arch. Microbiol. 144, 324-333).
      To assess the possible involvement of the MurE activity in the incorporation of D
      lysine, the murE gene from this organism was cloned in Escherichia coli, and the
      corresponding protein was purified as the C-terminal His6-tagged form. In vitro
      assays showed that D-lysine and meso-diaminopimelic acid were added to UDP-N
      acetylmuramoyl-dipeptide with 25 and 10% efficiencies, respectively, relative to
      L-lysine. The purified enzyme was used to synthesize the L- and D-lysine
      containing UDP-N-acetylmuramoyl-tripeptides; chemical analysis revealed an
      unusual structure for the D-lysine-containing nucleotide, namely acylation of the
      epsilon-amino function of D-lysine by the D-glutamyl residue. In vitro assays
      with MurF and MraY enzymes from T. maritima showed that this novel nucleotide was
      not a substrate for MurF but that it could be directly processed into tripeptide
      lipid I by MraY, thereby substantiating the role of MurE in the incorporation of
      D-lysine into peptidoglycan.

PMID- 16595663
TI  - Active transcription of the human FASL/CD95L/TNFSF6 promoter region in T
      lymphocytes involves chromatin remodeling: role of DNA methylation and protein
      acetylation suggest distinct mechanisms of transcriptional repression.
AB  - Fas ligand (FasL/CD95L/TNFSF6), a member of the tumor necrosis factor family,
      initiates apoptosis in lymphoid and nonlymphoid tissues by binding to its
      receptor Fas (CD95/TNFRSF6). Although the transcriptional control of TNFSF6 gene
      expression is subjected to intense study, the role of its chromatin organization
      and accessibility to the transcriptional machinery is not known. Here, we
      determined the chromatin organization of TNFSF6 gene 5' regulatory regions. Using
      the indirect end-labeling technique, a unique region named HSS1 and encompassing
      nucleotides -189 to +185 according to the transcriptional start site, was
      identified throughout a 20-kilobase nucleosomal DNA domain surrounding the
      promoter. The HSS1 region displayed hypersensitivity to in vivo DNase I digestion
      in TNFSF6-expressing cells only, including upon T cell activation.
      Hypersensitivity to micrococcal nuclease digestion and to specific restriction
      enzyme digestion suggested the precise positioning of two nucleosomes across the
      transcription start site and minimal promoter region, likely interfering with
      TNFSF6 active transcription in T lymphocytes. Indeed, HSS1 hypersensitivity to
      nuclease digestion strictly correlated with TNFSF6 transcription, including in
      primary and leukemia T cells. HSS1 chromatin remodeling preceded detectable
      TNFSF6 mRNA accumulation and was blocked by cycloheximide that also prevented
      TNFSF6 transcription. However, DNA methylation levels of the TNFSF6 HSS1 region
      did not correlate with transcriptional activation. Induction of global protein
      acetylation by treatment with histone deacetylase inhibitors was not accompanied
      by HSS1 chromatin remodeling and/or TNFSF6 transcription. We conclude that
      chromatin remodeling is a primary event in the activation of TNFSF6 expression in
      primary and leukemia T cells and that mechanisms independent of protein
      deacetylation and of DNA methylation of the TNFSF6 promoter region are involved
      in the repression of TNFSF6 gene expression.

PMID- 16595664
TI  - Human Mediator enhances basal transcription by facilitating recruitment of
      transcription factor IIB during preinitiation complex assembly.
AB  - The multisubunit Mediator is a well established transcription coactivator for
      gene-specific activators. However, recent studies have shown that, although not
      essential for basal transcription by purified RNA polymerase II (pol II) and
      general initiation factors, Mediator is essential for basal transcription in
      nuclear extracts that contain a more physiological complement of factors
      (Mittler, G., Kremmer, E., Timmers, H. T., and Meisterernst, M. (2001) EMBO Rep.
      2, 808-813; Baek, H. J., Malik, S., Qin, J., and Roeder, R. G. (2002) Mol. Cell.
      Biol. 22, 2842-2852). Here, mechanistic studies with immobilized DNA templates,
      purified factors, and factor-depleted HeLa extracts have shown (i) that Mediator
      enhancement of basal transcription correlates with Mediator-dependent recruitment
      of pol II and general initiation factors (transcription factor (TF) IIB and
      TFIIE) to the promoter; (ii) that Mediator and TFIIB, which both interact with
      pol II, are jointly required for pol II recruitment to the promoter and that
      TFIIB recruitment is Mediator-dependent, whereas Mediator recruitment is TFIIB
      independent; (iii) that a high level of TFIIB can bypass the Mediator requirement
      for basal transcription and pol II recruitment in nuclear extract, thus
      indicating a conditional restriction of TFIIB function and a key role of Mediator
      in overcoming this restriction; and (iv) that an earlier rate-limiting step
      involves formation of a TFIID-Mediator-promoter complex. These results support a
      stepwise assembly model, rather than a preformed holoenzyme model, for Mediator
      dependent assembly of a basal preinitiation complex and, more important, identify
      a step involving TFIIB as a key site of action of Mediator.

PMID- 16595665
TI  - Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire
      ebolavirus bind a common receptor.
AB  - The GP(1,2) envelope glycoproteins (GP) of filoviruses (marburg- and
      ebolaviruses) mediate cell-surface attachment, membrane fusion, and entry into
      permissive cells. Here we show that a 151-amino acid fragment of the Lake
      Victoria marburgvirus GP1 subunit bound filovirus-permissive cell lines more
      efficiently than full-length GP1. An homologous 148-amino acid fragment of the
      Zaire ebolavirus GP1 subunit similarly bound the same cell lines more efficiently
      than a series of longer GP1 truncation variants. Neither the marburgvirus GP1
      fragment nor that of ebolavirus bound a nonpermissive lymphocyte cell line. Both
      fragments specifically inhibited replication of infectious Zaire ebolavirus, as
      well as entry of retroviruses pseudotyped with either Lake Victoria marburgvirus
      or Zaire ebolavirus GP(1,2). These studies identify the receptor-binding domains
      of both viruses, indicate that these viruses utilize a common receptor, and
      suggest that a single small molecule or vaccine can be developed to inhibit
      infection of all filoviruses.

PMID- 16595666
TI  - UvrB domain 4, an autoinhibitory gate for regulation of DNA binding and ATPase
      activity.
AB  - UvrB, a central DNA damage recognition protein in bacterial nucleotide excision
      repair, has weak affinity for DNA, and its ATPase activity is activated by UvrA
      and damaged DNA. Regulation of DNA binding and ATP hydrolysis by UvrB is poorly
      understood. Using atomic force microscopy and biochemical assays, we found that
      truncation of domain 4 of Bacillus caldotenax UvrB (UvrBDelta4) leads to multiple
      changes in protein function. Protein dimerization decreases with an approximately
      8-fold increase of the equilibrium dissociation constant and an increase in DNA
      binding. Loss of domain 4 causes the DNA binding mode of UvrB to change from
      dimer to monomer, and affinity increases with the apparent dissociation constants
      on nondamaged and damaged single-stranded DNA decreasing 22- and 14-fold,
      respectively. ATPase activity by UvrBDelta4 increases 14- and 9-fold with and
      without single-stranded DNA, respectively, and UvrBDelta4 supports UvrA
      independent damage-specific incision by Cho on a bubble DNA substrate. We propose
      that other than its previously discovered role in regulating protein-protein
      interactions, domain 4 is an autoinhibitory domain regulating the DNA binding and
      ATPase activities of UvrB.

PMID- 16595667
TI  - Arabidopsis thaliana VTC4 encodes L-galactose-1-P phosphatase, a plant ascorbic
      acid biosynthetic enzyme.
AB  - In plants, a proposed ascorbate (vitamin C) biosynthesis pathway occurs via GDP-D
      mannose (GDP-D-Man), GDP-L-galactose (GDP-L-Gal), and L-galactose. However, the
      steps involved in the synthesis of L-Gal from GDP-L-Gal in planta are not fully
      characterized. Here we present evidence for an in vivo role for L-Gal-1-P
      phosphatase in plant ascorbate biosynthesis. We have characterized a low
      ascorbate mutant (vtc4-1) of Arabidopsis thaliana, which exhibits decreased
      ascorbate biosynthesis. Genetic mapping and sequencing of the VTC4 locus
      identified a mutation (P92L) in a gene with predicted L-Gal-1-P phosphatase
      activity (At3g02870). Pro-92 is within a beta-bulge that is conserved in related
      myo-inositol monophosphatases. The mutation is predicted to disrupt the
      positioning of catalytic amino acid residues within the active site. Accordingly,
      L-Gal-1-P phosphatase activity in vtc4-1 was approximately 50% of wild-type
      plants. In addition, vtc4-1 plants incorporate significantly more radiolabel from
      [2-(3)H]Man into L-galactosyl residues suggesting that the mutation increases the
      availability of GDP-L-Gal for polysaccharide synthesis. Finally, a homozygous T
      DNA insertion line, which lacks a functional At3g02870 gene product, is also
      ascorbate-deficient (50% of wild type) and deficient in L-Gal-1-P phosphatase
      activity. Genetic complementation tests revealed that the insertion mutant and
      VTC4-1 are alleles of the same genetic locus. The significantly lower ascorbate
      and perturbed L-Gal metabolism in vtc4-1 and the T-DNA insertion mutant indicate
      that L-Gal-1-P phosphatase plays a role in plant ascorbate biosynthesis. The
      presence of ascorbate in the T-DNA insertion mutant suggests there is a bypass to
      this enzyme or that other pathways also contribute to ascorbate biosynthesis.

PMID- 16595668
TI  - Mutagenesis and molecular modeling reveal the importance of the 5-HT3 receptor F
      loop.
AB  - The 5-HT(3) receptor is a member of the Cys-loop family of ligand-gated ion
      channels. The extracellular domains of these proteins contain six amino acid
      loops (A-F) that converge to form the ligand binding site. In this study we have
      mutated 21 residues in or close to the 5-HT(3) receptor F-loop (Ile(192) to
      Gly(212)) to Ala or to a residue with similar chemical properties. Mutant
      receptors were expressed in HEK293 cells, and binding affinity was measured using
      [(3)H]granisetron. Two regions displayed decreases in binding affinity when
      mutated to Ala (Ile(192)-Arg(196) and Asp(204)-Ser(206)), but only one region was
      sensitive when mutated to chemically similar residues (Ile(192)-Val(201)).
      Homology modeling using acetylcholine-binding protein crystal structures with a
      variety of different bound ligands suggests there may be distinct movements of
      Trp(195) and Asp(204) upon ligand binding, indicating that these residues and
      their immediate neighbors have the ability to interact differently with different
      ligands. The models suggest predominantly lateral movement around Asp(204) and
      rotational movement around Trp(195), indicating the former is in a more flexible
      region. Overall our results are consistent with a flexible 5-HT(3) receptor F
      loop with two regions that have specific but distinct roles in ligand binding.

PMID- 16595669
TI  - Perilipin promotes hormone-sensitive lipase-mediated adipocyte lipolysis via
      phosphorylation-dependent and -independent mechanisms.
AB  - Hormone-sensitive lipase (HSL) is the predominant lipase effector of
      catecholamine-stimulated lipolysis in adipocytes. HSL-dependent lipolysis in
      response to catecholamines is mediated by protein kinase A (PKA)-dependent
      phosphorylation of perilipin A (Peri A), an essential lipid droplet (LD)
      associated protein. It is believed that perilipin phosphorylation is essential
      for the translocation of HSL from the cytosol to the LD, a key event in
      stimulated lipolysis. Using adipocytes retrovirally engineered from murine
      embryonic fibroblasts of perilipin null mice (Peri-/- MEF), we demonstrate by
      cell fractionation and confocal microscopy that up to 50% of cellular HSL is LD
      associated in the basal state and that PKA-stimulated HSL translocation is fully
      supported by adenoviral expression of a mutant perilipin lacking all six PKA
      sites (Peri Adelta1-6). PKA-stimulated HSL translocation was confirmed in
      differentiated brown adipocytes from perilipin null mice expressing an adipose
      specific Peri Adelta1-6 transgene. Thus, PKA-induced HSL translocation was
      independent of perilipin phosphorylation. However, Peri Adelta1-6 failed to
      enhance PKA-stimulated lipolysis in either MEF adipocytes or differentiated brown
      adipocytes. Thus, the lipolytic action(s) of HSL at the LD surface requires PKA
      dependent perilipin phosphorylation. In Peri-/- MEF adipocytes, PKA activation
      significantly enhanced the amount of HSL that could be cross-linked to and co
      immunoprecipitated with ectopic Peri A. Notably, this enhanced cross-linking was
      blunted in Peri-/- MEF adipocytes expressing Peri Adelta1-6. This suggests that
      PKA-dependent perilipin phosphorylation facilitates (either direct or indirect)
      perilipin interaction with LD-associated HSL. These results redefine and expand
      our understanding of how perilipin regulates HSL-mediated lipolysis in
      adipocytes.

PMID- 16595670
TI  - Structural basis of the sphingomyelin phosphodiesterase activity in neutral
      sphingomyelinase from Bacillus cereus.
AB  - Sphingomyelinase (SMase) from Bacillus cereus (Bc-SMase) hydrolyzes sphingomyelin
      to phosphocholine and ceramide in a divalent metal ion-dependent manner. Bc-SMase
      is a homologue of mammalian neutral SMase (nSMase) and mimics the actions of the
      endogenous mammalian nSMase in causing differentiation, development, aging, and
      apoptosis. Thus Bc-SMase may be a good model for the poorly characterized
      mammalian nSMase. The metal ion activation of sphingomyelinase activity of Bc
      SMase was in the order Co2+ > or = Mn2+ > or = Mg2+ >> Ca2+ > or = Sr2+. The
      first crystal structures of Bc-SMase bound to Co2+, Mg2+, or Ca2+ were
      determined. The water-bridged double divalent metal ions at the center of the
      cleft in both the Co2+- and Mg2+-bound forms were concluded to be the catalytic
      architecture required for sphingomyelinase activity. In contrast, the
      architecture of Ca2+ binding at the site showed only one binding site. A further
      single metal-binding site exists at one side edge of the cleft. Based on the
      highly conserved nature of the residues of the binding sites, the crystal
      structure of Bc-SMase with bound Mg2+ or Co2+ may provide a common structural
      framework applicable to phosphohydrolases belonging to the DNase I-like folding
      superfamily. In addition, the structural features and site-directed mutagenesis
      suggest that the specific beta-hairpin with the aromatic amino acid residues
      participates in binding to the membrane-bound sphingomyelin substrate.

PMID- 16595671
TI  - The inhibitory gamma subunit of the rod cGMP phosphodiesterase binds the
      catalytic subunits in an extended linear structure.
AB  - The unique feature of rod photoreceptor cGMP phosphodiesterase (PDE6) is the
      presence of inhibitory subunits (Pgamma), which interact with the catalytic
      heterodimer (Palphabeta) to regulate its activity. This uniqueness results in an
      extremely high sensitivity and sophisticated modulations of rod visual signaling
      where the Pgamma/Palphabeta interactions play a critical role. The quaternary
      organization of the alphabetagammagamma heterotetramer is poorly understood and
      contradictory patterns of interaction have been previously suggested. Here we
      provide evidence that supports a specific interaction, by systematically and
      differentially analyzing the Pgamma-binding regions on Palpha and Pbeta through
      photolabel transfer from various Pgamma positions throughout the entire molecule.
      The Pgamma N-terminal Val16-Phe30 region was found to interact with the
      Palphabeta GAFa domain, whereas its C terminus (Phe73-Ile87) interacted with the
      Palphabeta catalytic domain. The interactions of Pgamma with these two domains
      were bridged by its central Ser40-Phe50 region through interactions with GAFb and
      the linker between GAFb and the catalytic domain, indicating a linear and
      extended interaction between Pgamma and Palphabeta. Furthermore, a photocross
      linked product alphabetagamma(gamma) was specifically generated by the double
      derivatized Pgamma, in which one photoprobe was located in the polycationic
      region and the other in the C terminus. Taken together the evidence supports the
      conclusion that each Pgamma molecule binds Palphabeta in an extended linear
      interaction and may even interact with both Palpha and Pbeta simultaneously.

PMID- 16595672
TI  - The reaction of phosphohexomutase from Pseudomonas aeruginosa: structural
      insights into a simple processive enzyme.
AB  - The enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) from Pseudomonas
      aeruginosa catalyzes the reversible conversion of 1-phospho to 6-phospho-sugars.
      The reaction entails two phosphoryl transfers, with an intervening 180 degrees
      reorientation of the reaction intermediate (e.g. glucose 1,6-bisphosphate) during
      catalysis. Reorientation of the intermediate occurs without dissociation from the
      active site of the enzyme and is, thus, a simple example of processivity, as
      defined by multiple rounds of catalysis without release of substrate. Structural
      characterization of two PMM/PGM-intermediate complexes with glucose 1,6
      bisphosphate provides new insights into the reaction catalyzed by the enzyme,
      including the reorientation of the intermediate. Kinetic analyses of site
      directed mutants prompted by the structural studies reveal active site residues
      critical for maintaining association with glucose 1,6-bisphosphate during its
      unique dynamic reorientation in the active site of PMM/PGM.

PMID- 16595673
TI  - Copper-mediated amyloid-beta toxicity is associated with an intermolecular
      histidine bridge.
AB  - Amyloid-beta peptide (Abeta) is pivotal to the pathogenesis of Alzheimer disease.
      Here we report the formation of a toxic Abeta-Cu2+ complex formed via a histidine
      bridged dimer, as observed at Cu2+/peptide ratios of >0.6:1 by EPR spectroscopy.
      The toxicity of the Abeta-Cu2+ complex to cultured primary cortical neurons was
      attenuated when either the pi -or tau-nitrogen of the imidazole side chains of
      His were methylated, thereby inhibiting formation of the His bridge. Toxicity did
      not correlate with the ability to form amyloid or perturb the acyl-chain region
      of a lipid membrane as measured by diphenyl-1,3,5-hexatriene anisotropy, but did
      correlate with lipid peroxidation and dityrosine formation. 31P magic angle
      spinning solid-state NMR showed that Abeta and Abeta-Cu2+ complexes interacted at
      the surface of a lipid membrane. These findings indicate that the generation of
      the Abeta toxic species is modulated by the Cu2+ concentration and the ability to
      form an intermolecular His bridge.

PMID- 16595674
TI  - Differential sorting of the vesicular glutamate transporter 1 into a defined
      vesicular pool is regulated by light signaling involving the clock gene Period2.
AB  - Synaptic strength depends on the amount of neurotransmitter stored in synaptic
      vesicles. The vesicular transmitter content has recently been shown to be
      directly dependent on the expression levels of vesicular neurotransmitter
      transporters indicating that the transport capacity of synaptic vesicles is a
      critical determinant for synaptic efficacy. Using synaptic vesicles prepared from
      whole brain at different times of the day we now show that the amount of
      vesicular glutamate transporter (VGLUT) 1 undergoes strong diurnal cycling.
      VGLUT1 protein levels are high before the start of the light period, decline at
      noon, increase again before start of the dark period, and decline again at
      midnight. Mice kept in complete darkness showed within a 24-h period only a
      single peak of VGLUT1 expression in the middle of the rest phase. In contrast,
      mice lacking the period gene Period 2, a core component of the circadian clock,
      did not show any light-cycle-dependent changes of VGLUT1 levels. No other of
      several synaptic vesicle proteins examined underwent circadian cycling. Circadian
      cycling of VGLUT1 was not seen when analyzing homogenate or synaptosomes, the
      starting fraction for vesicle preparation. Circadian cycling of VGLUT1 was also
      not reflected at the mRNA level. We conclude that nerve terminals are endowed
      with mechanisms that regulate quantal size by changing the copy number of
      transporters in synaptic vesicles. A reduced amount of VGLUT1 per vesicle is
      probably achieved by means of selective sorting controlled by clock genes.

PMID- 16595675
TI  - Calcyon, a novel partner of clathrin light chain, stimulates clathrin-mediated
      endocytosis.
AB  - In the central nervous system, clathrin-mediated endocytosis is crucial for
      efficient synaptic transmission. Clathrin-coated vesicle assembly and disassembly
      is regulated by some 30 adaptor and accessory proteins, most of which interact
      with clathrin heavy chain. Using the calcyon cytosolic domain as bait, we
      isolated clathrin light chain in a yeast two-hybrid screen. The interaction
      domain was mapped to the heavy chain binding domain and C-terminal regions of
      light chain. Further, the addition of the calcyon C terminus stimulated clathrin
      self-assembly in a dose-dependent fashion. Calcyon, which is a single
      transmembrane protein predominantly expressed in brain, localized to vesicular
      compartments within pre- and postsynaptic structures. There was a high degree of
      overlap in the distribution of LC and calcyon in neuronal dendrites, spines, and
      cell bodies. Co-immunoprecipitation studies further suggested an association of
      calcyon with the clathrin-mediated endocytic machinery. Compared with controls,
      HEK293 cells overexpressing calcyon exhibited significantly enhanced transferrin
      uptake but equivalent levels of recycling. Conversely, transferrin uptake was
      largely abolished in neocortical neurons obtained from mice homozygous for a
      calcyon null allele, whereas recycling proceeded at wild type levels.
      Collectively, these data indicate a role for calcyon in clathrin-mediated
      endocytosis in brain.

PMID- 16595676
TI  - Knocking down type 2 but not type 1 calsequestrin reduces calcium sequestration
      and release in C2C12 skeletal muscle myotubes.
AB  - We examined the roles of type 1 and type 2 calsequestrins (CSQ1 and CSQ2) in
      stored Ca2+ release of C2C12 skeletal muscle myotubes. Transduction of C2C12
      myoblasts with CSQ1 or CSQ2 small interfering RNAs effectively reduced the
      expression of targeted CSQ protein to near undetectable levels. As compared with
      control infected or CSQ1 knockdown myotubes, CSQ2 and CSQ1/CSQ2 knockdown
      myotubes had significantly reduced stored Ca2+ release evoked by activators of
      intracellular Ca2+ release channel/ryanodine receptor (10 mM caffeine, 200 microM
      4-chloro-m-cresol, or 10 mM KCl). Thus, CSQ1 is not essential for effective
      stored Ca2+ release in C2C12 myotubes despite our in vitro studies suggesting
      that CSQ1 may enhance ryanodine receptor channel activity. To determine the basis
      of the reduced stored Ca2+ release in CSQ2 knockdown myotubes, we performed
      immunoblot analyses and found a significant reduction in both sarco/endoplasmic
      reticulum Ca2+-ATPase and skeletal muscle ryanodine receptor proteins in CSQ2 and
      CSQ1/CSQ2 knockdown myotubes. Moreover, these knockdown myotubes exhibited
      reduced Ca2+ uptake and reduced stored Ca2+ release by UTP (400 microM) that
      activates a different family of intracellular Ca2+ release channels (inositol
      1,4,5-trisphosphate receptors). Taken together, our data suggest that knocking
      down CSQ2, but not CSQ1, leads to reduced Ca2+ storage and release in C2C12
      myotubes.

PMID- 16595677
TI  - Identification of a novel arabinofuranosyltransferase (AftA) involved in cell
      wall arabinan biosynthesis in Mycobacterium tuberculosis.
AB  - The cell wall mycolyl-arabinogalactan-peptidoglycan complex is essential in
      mycobacterial species, such as Mycobacterium tuberculosis, and is the target of
      several anti-tubercular drugs. For instance, ethambutol targets arabinogalactan
      biosynthesis through inhibition of the arabinofuranosyltransferases Mt-EmbA and
      Mt-EmbB. Following a detailed bioinformatics analysis of genes surrounding the
      conserved emb locus, we present the identification and characterization of a
      novel arabinofuranosyltransferase AftA (Rv3792). The enzyme catalyzes the
      addition of the first key arabinofuranosyl residue from the sugar donor beta-D
      arabinofuranosyl-1-monophosphoryldecaprenol to the galactan domain of the cell
      wall, thus "priming" the galactan for further elaboration by the
      arabinofuranosyltransferases. Because aftA is an essential gene in M.
      tuberculosis, we deleted its orthologue in Corynebacterium glutamicum to produce
      a slow growing but viable mutant. Analysis of its cell wall revealed the complete
      absence of arabinose resulting in a truncated cell wall structure possessing only
      a galactan core with a concomitant loss of cell wall-bound mycolates.
      Complementation of the mutant was fully restored to the wild type phenotype by Cg
      aftA. In addition, by developing an in vitro assay using recombinant Escherichia
      coli expressing Mt-aftA and use of cell wall galactan as an acceptor, we
      demonstrated the transfer of arabinose from beta-D-arabinofuranosyl-1
      monophosphoryldecaprenol to galactan, and unlike the Mt-Emb proteins, Mt-AftA was
      not inhibited by ethambutol. This newly discovered glycosyltransferase represents
      an attractive drug target for further exploitation by chemotherapeutic
      intervention.

PMID- 16595678
TI  - Identification of key functional domains in the C terminus of the K+-Cl-
      cotransporters.
AB  - The K+-Cl- cotransporter (KCC) isoforms constitute a functionally heterogeneous
      group of ion carriers. Emerging evidence suggests that the C terminus (Ct) of
      these proteins is important in conveying isoform-specific traits and that it may
      harbor interacting sites for 4beta-phorbol 12-myristate 13-acetate (PMA)-induced
      effectors. In this study, we have generated KCC2-KCC4 chimeras to identify key
      functional domains in the Ct of these carriers and single point mutations to
      determine whether canonical protein kinase C sites underlie KCC2-specific
      behaviors. Functional characterization of wild-type (wt) and mutant carriers in
      Xenopus laevis oocytes showed for the first time that the KCCs do not exhibit
      similar sensitivities to changes in osmolality and that this distinguishing
      feature as well as differences in transport activity under both hypotonic and
      isotonic conditions are in part determined by the residue composition of the
      distal Ct. At the same time, several mutations in this domain and in the proximal
      Ct of the KCCs were found to generate allosteric-like effects, suggesting that
      the regions analyzed are important in defining conformational ensembles and that
      isoform-specific structural configurations could thus account for variant
      functional traits as well. Characterization of the other mutants in this work
      showed that KCC2 is not inhibited by PMA through phosphorylation of its canonical
      protein kinase C sites. Intriguingly, however, the substitutions N728S and S940A
      were seen to alter the PMA effect paradoxically, suggesting again that allosteric
      changes in the Ct are important determinants of transport activity and,
      furthermore, that the structural configuration of this domain can convey specific
      functional traits by defining the accessibility of cotransporter sites to
      regulatory intermediates such as PMA-induced effectors.

PMID- 16595679
TI  - The nuclear localization of ERK2 occurs by mechanisms both independent of and
      dependent on energy.
AB  - The mitogen-activated protein (MAP) kinases ERK1 and ERK2 often accumulate in the
      nuclei of stimulated cells to mediate changes in transcription. The mechanisms
      underlying stimulus-dependent redistribution of these kinases remain unclear. We
      have used a permeabilized cell reconstitution assay in HeLa cells and human
      foreskin fibroblasts to explore the processes by which ERK2 enters and exits the
      nucleus. We previously reported that entry of unphosphorylated ERK2 into the
      nucleus occurs by facilitated diffusion not requiring cytosolic transport
      factors. We find that export, like import, can occur by an energy- and carrier
      independent mechanism. An energy-dependent mechanism of ERK2 export can also be
      distinguished, mediated at least in part through the exportin CRM1. We have also
      examined import and export of thiophosphorylated, active ERK2. Import of active
      ERK2 is significantly enhanced by the addition of exogenous transport factors and
      an energy regeneration system. These studies support a model in which multiple
      constitutive and regulated processes control the subcellular distribution of
      ERK2.

PMID- 16595680
TI  - KLF5 Interacts with p53 in regulating survivin expression in acute lymphoblastic
      leukemia.
AB  - The Kruppel-like factor 5 (KLF5) is a transcription factor that regulates
      cellular signaling involved in cell proliferation and oncogenesis. Here, we
      report that KLF5 interacts with tumor suppressor p53 in regulating the expression
      of the inhibitor-of-apoptosis protein survivin, which may play a role in
      pathological process of cancer. The core promoter region of survivin contains
      multiple GT-boxes that have been characterized as KLF5 response elements.
      Deletion and mutation analyses as well as chromatin immunoprecipitation and
      electronic mobility shift assay indicated that KLF5 binds to the core survivin
      promoter and strongly induces its activity. Furthermore, we demonstrated that
      KLF5 protein is able to bind to p53 and abrogate the p53-regulated repression of
      survivin. Transfection of KLF5 into a KLF5-negative acute lymphoblastic leukemia
      cell line EU-8 enhanced survivin expression, and conversely, silencing of KLF5 by
      small interfering RNA in a KLF5-overexpressing acute lymphoblastic leukemia cell
      line EU-4 down-regulated survivin expression. The KLF5 small interfering RNA
      mediated down-regulation of survivin sensitized EU-4 cells to apoptosis induced
      by chemotherapeutic drug doxorubicin. These findings identify a novel regulatory
      pathway for the expression of survivin under the control of KLF5 and p53.
      Deregulation of this pathway may result in overexpression of survivin in cancer,
      thus contributing to drug resistance.

PMID- 16595681
TI  - Pleiotropic effects of ATP.Mg2+ binding in the catalytic cycle of ubiquitin
      activating enzyme.
AB  - Conjugation of ubiquitin and other Class 1 ubiquitin-like polypeptides to
      specific protein targets serves diverse regulatory functions in eukaryotes. The
      obligatory first step of conjugation requires ATP-coupled activation of the
      ubiquitin-like protein by members of a superfamily of evolutionarily related
      enzymes. Kinetic and equilibrium studies of the human ubiquitin-activating enzyme
      (HsUba1a) reveal that mutations within the ATP.Mg(2+) binding site have
      remarkably pleiotropic effects on the catalytic phenotype of the enzyme. Mutation
      of Asp(576) or Lys(528) results in dramatically impaired binding affinities for
      ATP.Mg(2+), a shift from ordered to random addition in co-substrate binding, and
      a significantly reduced rate of ternary complex formation that shifts the rate
      limiting step to ubiquitin adenylate formation. Mutations at neither position
      affect the affinity of HsUbc2b binding; however, differences in k(cat) values
      determined from ternary complex formation versus HsUbc2b transthiolation suggest
      that binding of the E2 enhances the rate of bound ubiquitin adenylate formation.
      These results confirm that Asp(576) and Lys(528) are important for ATP.Mg(2+)
      binding but are essential catalytic groups for ubiquitin adenylate transition
      state stabilization. The latter mechanistic effect explicates the observed loss
      of-function phenotype associated with mutation of residues paralogous to Asp(576)
      within the activating enzymes for other ubiquitin-like proteins.

PMID- 16595682
TI  - Equimolar production of amyloid beta-protein and amyloid precursor protein
      intracellular domain from beta-carboxyl-terminal fragment by gamma-secretase.
AB  - We showed previously that cells expressing wild-type (WT) beta-amyloid precursor
      protein (APP) or coexpressing WTAPP and WT presenilin (PS) 1/2 produced APP
      intracellular domains (AICD) 49-99 and 50-99, with the latter predominating. On
      the other hand, the cells expressing mutant (MT) APP or coexpressing WTAPP and
      MTPS1/2 produced a greater proportion of AICD-(49-99) than AICD-(50-99). In
      addition, the expression of amyloid beta-protein (Abeta) 49 in cells resulted in
      predominant production of Abeta40 and that of Abeta48 leads to preferential
      production of Abeta42. These observations suggest that epsilon-cleavage and gamma
      cleavage are interrelated. To determine the stoichiometry between Abeta and AICD,
      we have established a 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1
      propanesulfonic acid-solubilized gamma-secretase assay system that exhibits high
      specific activity. By using this assay system, we have shown that equal amounts
      of Abeta and AICD are produced from beta-carboxyl-terminal fragment (C99) by
      gamma-secretase, irrespective of WT or MTAPP and PS1/2. Although various Abeta
      species, including Abeta40, Abeta42, Abeta43, Abeta45, Abeta48, and Abeta49, are
      generated, only two species of AICD, AICD-(49-99) and AICD-(50-99), are detected.
      We also have found that M233T MTPS1 produced only one species of AICD, AICD-(49
      99), and only one for its counterpart, Abeta48, in contrast to WT and other
      MTPS1s. These strongly suggest that epsilon-cleavage is the primary event, and
      the produced Abeta48 and Abeta49 rapidly undergo gamma-cleavage, resulting in
      generation of various Abeta species.

PMID- 16595683
TI  - Hyaluronan synthesis induces microvillus-like cell surface protrusions.
AB  - Hyaluronan synthases (HASs) are plasma membrane enzymes that simultaneously
      elongate, bind, and extrude the growing hyaluronan chain directly into
      extracellular space. In cells transfected with green fluorescent protein (GFP)
      tagged Has3, the dorsal surface was decorated by up to 150 slender, 3-20-microm
      long microvillus-type plasma membrane protrusions, which also contained
      filamentous actin, the hyaluronan receptor CD44, and lipid raft microdomains.
      Enzymatic activity of HAS was required for the growth of the microvilli, which
      were not present in cells transfected with other GFP proteins or inactive GFP
      Has3 mutants or in cells incubated with exogenous soluble hyaluronan. The
      microvilli induced by HAS3 were gradually withered by introduction of an
      inhibitor of hyaluronan synthesis and rapidly retracted by hyaluronidase
      digestion, whereas they were not affected by competition with hyaluronan
      oligosaccharides and disruption of the CD44 gene, suggesting independence of
      hyaluronan receptors. The data bring out the novel concept that the glycocalyx
      created by dense arrays of hyaluronan chains, tethered to HAS during
      biosynthesis, can induce and maintain prominent microvilli.

PMID- 16595684
TI  - Intracellular trafficking of KA2 kainate receptors mediated by interactions with
      coatomer protein complex I (COPI) and 14-3-3 chaperone systems.
AB  - Assembly and trafficking of neurotransmitter receptors are processes contingent
      upon interactions between intracellular chaperone systems and discrete
      determinants in the receptor proteins. Kainate receptor subunits, which form
      ionotropic glutamate receptors with diverse roles in the central nervous system,
      contain a variety of trafficking determinants that promote either membrane
      expression or intracellular sequestration. In this report, we identify the
      coatomer protein complex I (COPI) vesicle coat as a critical mechanism for
      retention of the kainate receptor subunit KA2 in the endoplasmic reticulum. COPI
      subunits immunoprecipitated with KA2 subunits from both cerebellum and COS-7
      cells, and beta-COP protein interacted directly with immobilized KA2 peptides
      containing the arginine-rich retention/retrieval determinant. Association between
      COPI proteins and KA2 subunits was significantly reduced upon alanine
      substitution of this signal in the cytoplasmic tail of KA2. Temperature-sensitive
      degradation of COPI complex proteins was correlated with an increase in plasma
      membrane localization of the homologous KA2 receptor. Assembly of heteromeric
      GluR6a/KA2 receptors markedly reduced association of KA2 and COPI. Finally, the
      reduction in COPI binding was correlated with an increased association with 14-3
      3 proteins, which mediate forward trafficking of other integral signaling
      proteins. These interactions therefore represent a critical early checkpoint for
      biosynthesis of functional KARs.

PMID- 16595685
TI  - Multivariate design and evaluation of a set of RGRPQ-derived innate immunity
      peptides.
AB  - Oral commensal Streptococcus gordonii proteolytically cleave the salivary PRP-1
      polypeptide into an RGRPQ innate peptide. The Arg and Gln termini are crucial for
      RGRPQ-mediated ammonia production and proliferation by S. gordonii SK12 and
      adhesion inhibition and desorption by Actinomyces naeslundii T14V, respectively.
      Here we have applied (i) a multivariate approach using RGRPQ-related peptides
      varied at amino acids 2, 3, and 4 simultaneously and (ii) size and N- and C
      terminal modifications of RGRPQ to generate structure activity information. While
      the N-terminal arginine motif mediated ammonia production independent of peptide
      size, other responses required more or less full-length peptide motifs. The
      motifs for adhesion inhibition and desorption were the same. The adhesion and
      proliferation motifs required similarly a hydrophobic/low polarity amino acid 4
      but differentially a hydrophilic or hydrophobic character of amino acids 2/3,
      respectively; polar peptides with small/hydrophilic and hydrophilic amino acids 2
      and 3, respectively, had high adhesion inhibition/desorption activity, and
      lipophilic peptides with large/hydrophobic amino acids 2 and 3 had high
      proliferation activity. Accordingly, while RIWWQ had increased proliferation but
      abolished adhesion/desorption activity, peptides designed with hydrophilic amino
      acids 2 and 3 were predicted to behave in the opposite way. Moreover, a RGRPQ
      mimetic for all three responses should mimic small hydrophilic, large nitrogen
      containing, and hydrophobic/low polarity amino acids 2, 3, and 4, respectively.
      Peptides fulfilling these criteria were 1-1.6-fold improved in all three
      responses. Thus, both mimetics and peptides with differential proliferation and
      adhesion activities may be generated for evaluation in biofilm models.

PMID- 16595686
TI  - Highly selective hydrolysis of fatty acyl-CoAs by calcium-independent
      phospholipase A2beta. Enzyme autoacylation and acyl-CoA-mediated reversal of
      calmodulin inhibition of phospholipase A2 activity.
AB  - Calcium-independent phospholipase A2beta (iPLA2beta) participates in numerous
      diverse cellular processes, such as arachidonic acid release, insulin secretion,
      calcium signaling, and apoptosis. Herein, we demonstrate the highly selective
      iPLA2beta-catalyzed hydrolysis of saturated long-chain fatty acyl-CoAs (palmitoyl
      CoA approximately myristoyl-CoA >> stearoyl-CoA >> oleoyl-CoA approximately =
      arachidonoyl-CoA) present either as monomers in solution or guests in host
      membrane bilayers. Site-directed mutagenesis of the iPLA2beta catalytic serine
      (S465A) completely abolished acyl-CoA thioesterase activity, demonstrating that
      Ser-465 catalyzes both phospholipid and acyl-CoA hydrolysis. Remarkably,
      incubation of iPLA2beta with oleoyl-CoA, but not other long-chain acyl-CoAs,
      resulted in robust stoichiometric covalent acylation of the enzyme. Moreover,
      S465A mutagenesis or pretreatment of wild-type iPLA2beta with (E)-6
      (bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one unexpectedly
      increased acylation of the enzyme, indicating the presence of a second reactive
      nucleophilic residue that participates in the formation of the fatty acyl
      iPLA2beta adduct. Radiolabeling of intact Sf9 cells expressing iPLA2beta with
      [3H]oleic acid demonstrated oleoylation of the membrane-associated enzyme.
      Partial trypsinolysis of oleoylated iPLA2beta and matrix-assisted laser
      desorption ionization mass spectrometry analysis localized the acylation site to
      a hydrophobic 25-kDa fragment (residues approximately 400-600) spanning the
      active site to the calmodulin binding domain. Intriguingly, calmodulin-Ca2+
      blocked acylation of iPLA2beta by oleoyl-CoA. Remarkably, the addition of low
      micromolar concentrations (5 microM) of oleoyl-CoA resulted in reversal of
      calmodulin-mediated inhibition of iPLA2 beta phospholipase A2 activity. These
      results collectively identify the molecular species-specific acyl-CoA
      thioesterase activity of iPLA2beta, demonstrate the presence of a second active
      site that mediates iPLA2beta autoacylation, and identify long-chain acyl-CoAs as
      potential candidates mediating calcium influx factor activity.

PMID- 16595687
TI  - Internal ribosome entry site-mediated translation of Apaf-1, but not XIAP, is
      regulated during UV-induced cell death.
AB  - Components of the cellular translation machinery are targets of caspase-mediated
      cleavage during apoptosis that correlates with the inhibition of protein
      synthesis, which accompanies apoptosis. Paradoxically, protein synthesis is
      required for apoptosis to occur in many experimental settings. Previous studies
      showed that two proteins that regulate apoptosis by controlling caspase activity,
      XIAP and Apaf-1, are translated by a unique, cap-independent mechanism mediated
      by an internal ribosome entry site (IRES) that is used preferentially under
      conditions in which normal cap-dependent translation is repressed. We
      investigated the regulation of XIAP and Apaf-1 following UVC irradiation. We show
      that UVC irradiation leads to the inhibition of translation and cell death.
      Furthermore, IRES-mediated translation of Apaf-1, but not XIAP, is enhanced by
      UVC irradiation, and this increase in Apaf-1 translation correlated with cell
      death. The enhanced Apaf-1 IRES-mediated translation is caspase-independent but
      is negatively modulated by the eIF2alpha kinase protein kinase RNA-like
      endoplasmic reticulum kinase. These data suggest that progression of UV-induced
      apoptosis requires IRES-mediated translation of Apaf-1 to ensure continuous
      levels of Apaf-1 despite an overall suppression of protein synthesis.

PMID- 16595688
TI  - Solution structure of human peptidyl prolyl isomerase-like protein 1 and insights
      into its interaction with SKIP.
AB  - The human PPIL1 (peptidyl prolyl isomerase-like protein 1) is a specific
      component of human 35 S U5 small nuclear ribonucleoprotein particle and 45 S
      activated spliceosome. It is recruited by SKIP, another essential component of 45
      S activated spliceosome, into spliceosome just before the catalytic step 1. It
      stably associates with SKIP, which also exists in 35 S and activated spliceosome
      as a nuclear matrix protein. We report here the solution structure of PPIL1
      determined by NMR spectroscopy. The structure of PPIL1 resembles other members of
      the cyclophilin family and exhibits PPIase activity. To investigate its
      interaction with SKIP in vitro, we identified the SKIP contact region by GST
      pulldown experiments and surface plasmon resonance. We provide direct evidence of
      PPIL1 stably associated with SKIP. The dissociation constant is 1.25 x 10(-7) M
      for the N-terminal peptide of SKIP-(59-129) with PPIL1. We also used chemical
      shift perturbation experiments to show the possible SKIP binding interface on
      PPIL1. These results illustrated that a novel cyclophilin-protein contact mode
      exists in the PPIL1-SKIP complex during activation of the spliceosome. The
      biological implication of this binding with spliceosome rearrangement during
      activation is discussed.

PMID- 16595689
TI  - Functional expression of thermo-transient receptor potential channels in dental
      primary afferent neurons: implication for tooth pain.
AB  - Temperature signaling can be initiated by members of transient receptor potential
      family (thermo-TRP) channels. Hot and cold substances applied to teeth usually
      elicit pain sensation. This study investigated the expression of thermo-TRP
      channels in dental primary afferent neurons of the rat identified by retrograde
      labeling with a fluorescent dye in maxillary molars. Single cell reverse
      transcription-PCR and immunohistochemistry revealed expression of TRPV1, TRPM8,
      and TRPA1 in subsets of such neurons. Capsaicin (a TRPV1 agonist), menthol (a
      TRPM8 agonist), and icilin (a TRPM8 and TRPA1 agonist) increased intracellular
      calcium and evoked cationic currents in subsets of neurons, as did the
      appropriate temperature changes (>43 degrees , <25 degrees , and <17 degrees C,
      respectively). Some neurons expressed more than one TRP channel and responded to
      two or three corresponding stimuli (ligands or thermal stimuli).
      Immunohistochemistry and single cell reverse transcription-PCR following whole
      cell recordings provided direct evidence for the association between the
      responsiveness to thermo-TRP ligands and expression of thermo-TRP channels. The
      results suggest that activation of thermo-TRP channels expressed by dental
      afferent neurons contributes to tooth pain evoked by temperature stimuli.
      Accordingly, blockade of thermo-TRP channels will provide a novel therapeutic
      intervention for the treatment of tooth pain.

PMID- 16595690
TI  - Expression and characterization of full-length human huntingtin, an elongated
      HEAT repeat protein.
AB  - Huntington disease is an inherited neurodegenerative disorder that is caused by
      expanded CAG trinucleotide repeats, resulting in a polyglutamine stretch of >37
      on the N terminus of the protein huntingtin (htt). htt is a large (347 kDa),
      ubiquitously expressed protein. The precise functions of htt are not clear, but
      its importance is underscored by the embryonic lethal phenotype in htt knock-out
      mice. Despite the fact that the htt gene was cloned 13 years ago, little is known
      about the properties of the full-length protein. Here we report the expression
      and preliminary characterization of recombinant full-length wild-type human htt.
      Our results support a model of htt composed entirely of HEAT repeats that stack
      to form an elongated superhelix.

PMID- 16595691
TI  - Myelin-associated glycoprotein inhibits microtubule assembly by a Rho-kinase
      dependent mechanism.
AB  - Myelin-associated glycoprotein (MAG) and Nogo are potent inhibitors of neurite
      outgrowth from a variety of neurons, and they have been identified as possible
      components of the central nervous system myelin that prevents axonal regeneration
      in the adult vertebrate central nervous system. The activation of RhoA and Rho
      kinase is reported to be an essential part of the signaling mechanism of these
      proteins. Here, we report that the collapsing response mediator protein-2 (CRMP
      2) is phosphorylated by a Rho-kinase-dependent mechanism downstream of MAG or
      Nogo-66. The overexpression of the nonphosphorylated form of CRMP-2 at threonine
      555, which is the phosphorylation site for Rho-kinase, counteracts the inhibitory
      effect of MAG on the postnatal cerebellar neurons. Additionally, the expression
      of the dominant negative form of CRMP-2 or knockdown of the gene using small
      interference RNA (siRNA) mimics the effect of MAG in vitro. Consistent with the
      function of CRMP-2, which promotes microtubule assembly, microtubule levels are
      down-regulated in the cerebellar neurons that are stimulated with MAG in vitro.
      Reduction in the density of microtubules is also observed in the injured axons
      following the spinal cord injury, and this effect depends on the Rho-kinase
      activity. Our data suggest the important roles of CRMP-2 and microtubules in the
      inhibition of the axon regeneration by the myelin-derived inhibitors.

PMID- 16595692
TI  - NF-Y and CCAAT/enhancer-binding protein alpha synergistically activate the mouse
      amelogenin gene.
AB  - Amelogenin is the major protein component of the forming enamel matrix. In situ
      hybridization revealed a periodicity for amelogenin mRNA hybridization signals
      ranging from low to high transcript abundance on serial sections of developing
      mouse teeth. This in vivo observation led us to examine the amelogenin promoter
      for the activity of transcription factor(s) that account for this expression
      aspect of the regulation for the amelogenin gene. We have previously shown that
      CCAAT/enhancer-binding protein alpha (C/EBPalpha) is a potent transactivator of
      the mouse X-chromosomal amelogenin gene acting at the C/EBPalpha cis-element
      located in the -70/+52 minimal promoter. The minimal promoter contains a reversed
      CCAAT box (-58/-54) that is four base pairs downstream from the C/EBPalpha
      binding site. Similar to the C/EBPalpha binding site, the integrity of the
      reversed CCAAT box is also required for maintaining the activity of the basal
      promoter. We therefore focused on transcription factors that interact with the
      reversed CCAAT box. Using electrophoretic mobility shift assays we demonstrated
      that NF-Y was directly bound to this reversed CCAAT site. Co-transfection of
      C/EBPalpha and NF-Y synergistically increased the promoter activity. In contrast,
      increased expression of NF-Y alone had only marginal effects on the promoter. A
      dominant-negative DNA binding-deficient NF-Y mutant (NF-YAm29) dramatically
      decreased the promoter activity both in the absence or presence of exogenous
      expression of C/EBPalpha. We identified protein-protein interactions between
      C/EBPalpha and NF-Y by a co-immunoprecipitation analysis. These results suggest
      that C/EBPalpha and NF-Y synergistically activate the mouse amelogenin gene and
      can contribute to its physiological regulation during amelogenesis.

PMID- 16595693
TI  - Generation of a stable activated thrombin activable fibrinolysis inhibitor
      variant.
AB  - Activated thrombin activable fibrinolysis inhibitor (TAFIa), generated upon
      activation of TAFI, exerts an antifibrinolytic effect. TAFIa is a thermolabile
      enzyme, inactivated through a conformational change. The objective of the current
      study was to generate a stable variant of human TAFIa. Using a site-directed as
      well as a random mutagenesis approach to generate a library of TAFI mutants, we
      identified two mutations that increase TAFIa stability, i.e. a Ser305 to Cys and
      a Thr329 to Ile mutation, respectively. Combining these mutations in TAFI-Ala147
      Ile325, the most stable isoform of TAFIa (half-life of 9.4 +/- 0.4 min), revealed
      a TAFIa half-life of 70 +/- 3.1 min (i.e. an 11-fold increase versus 6.3 +/- 0.3
      min for TAFIa-Ala147-Thr325, the most frequently occurring isoform of TAFI in
      humans) at 37 degrees C. Moreover, clot lysis (induced by tissue plasminogen
      activator) experiments in which TAFI-Ala147-Cys305-Ile325-Ile329 was added to
      TAFI-depleted plasma revealed a 50% clot lysis time of 313 +/- 77 min (i.e. a 3.0
      fold increase versus 117 +/- 10 min for TAFI-Ala147-Thr325). The availability of
      a more stable TAFIa variant will facilitate the search for inhibitors and allow
      further structural analysis to elucidate the mechanisms of the instability of
      TAFIa.

PMID- 16595696
TI  - Steroid 5alpha-reductase isozymes in the adult female rat brain: central role of
      dihydrotestosterone.
AB  - The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms,
      5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2). 5alpha-R1 has been
      associated with catabolic functions whereas 5alpha-R2 has been associated with
      sexually dimorphic functions of the male. We recently demonstrated that both
      5alpha-R isozymes are present in the central nervous system (CNS) of the adult
      male rat and are regulated in an opposing way by androgens. This finding raises
      the question as to whether both isozymes play a role in the sexual dimorphism of
      the CNS, besides other functions. To test this hypothesis, it is essential to
      study the regulation of both isozymes by androgens in the female. In this work,
      we studied the effects of testosterone (T) and dihydrotestosterone (DHT) on mRNA
      levels of both 5alpha-R isoforms in the prefrontal cortex of the adult female rat
      by one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary
      electrophoresis. Our results demonstrate for the first time that 5alpha-R2 mRNA
      is slightly regulated by T and DHT in females. Surprisingly, 5alpha-R1 mRNA is
      not regulated by T in the intact female, whereas it is very positively regulated
      by DHT, a more potent androgen than T. These data indicate the great sexual
      dimorphism in the CNS with respect to both 5alpha-R isozymes, and suggest a
      crucial role of DHT in the sexual dimorphism of the CNS in the female. These
      results open up a new research line that may lead to a better understanding of
      the physiology of the CNS.

PMID- 16595694
TI  - Orphan nuclear receptor Nur77 induces zinc finger protein GIOT-1 gene expression,
      and GIOT-1 acts as a novel corepressor of orphan nuclear receptor SF-1 via
      recruitment of HDAC2.
AB  - Kruppel-associated box (KRAB) domain-containing proteins consist of potential
      transcriptional repression modules. Previously, gonadotropin-inducible ovarian
      transcription factor-1 (GIOT-1) was identified as a novel KRAB-containing zinc
      finger protein and shown to have transcriptional repression activity. Here, we
      demonstrate that orphan nuclear receptor Nur77 regulates GIOT-1 gene expression
      in testicular Leydig cell lines and that GIOT-1 acts as a novel corepressor of
      the orphan nuclear receptor steroidogenic factor 1 (SF-1). Mutation analysis of
      the GIOT-1 promoter and overexpression analysis of dominant-negative Nur77
      revealed that luteinizing hormone activates GIOT-1 gene expression through Nur77.
      Electrophoretic mobility shift and chromatin immunoprecipitation assays showed
      that Nur77 directly binds to the GIOT-1 promoter. GIOT-1 represses the SF-1
      transactivation, and specific interaction between GIOT-1 and SF-1 was observed.
      We also demonstrate an interaction between GIOT-1 and histone deacetylase 2
      (HDAC2). GIOT-1-mediated transrepression was recovered by down-regulation of
      HDAC2 expression with small interfering RNA of HDAC2. Knock down of the
      endogenous GIOT-1 results in significant enhancement of CYP17 expression in
      Leydig cells. In conclusion, this study of cross-talk between GIOT-1 and orphan
      nuclear receptors will provide new insights into the role of KRAB-containing zinc
      finger proteins in nuclear receptor action.

PMID- 16595695
TI  - A double Holliday junction dissolvasome comprising BLM, topoisomerase IIIalpha,
      and BLAP75.
AB  - Bloom syndrome (BS), an autosomal recessive disorder, is marked by a high
      incidence of cancer early in life. Cells derived from BS patients are unstable
      genetically and exhibit frequent sister chromatid exchanges, reflective of
      homologous recombination (HR) deregulation. BLM, the RecQ-like helicase mutated
      in BS, is found in several cellular protein complexes, all of which contain
      topoisomerase IIIalpha (Topo IIIalpha) and a novel protein BLAP75. Here, using
      highly purified human proteins, we show that BLAP75 associates independently with
      both Topo IIIalpha and BLM. Even though BLM and Topo IIIalpha can dissolve the
      double Holliday junction (DHJ) to yield non-crossover recombinants (1), under
      physiological conditions, DHJ dissolution becomes completely dependent on BLAP75.
      The effect of BLAP75 on BLM-Topo IIIalpha is highly specific, as it is not seen
      with the combination of Topo IIIalpha and Escherichia coli RecQ helicase or
      another human RecQ-like helicase WRN. Thus, BLM, Topo IIIalpha, and BLAP75
      constitute a dissolvasome complex that processes HR intermediates to limit DNA
      crossover formation. This function of the BLM-Topo IIIalpha-BLAP75 dissolvasome
      is likely indispensable for genome maintenance and cancer avoidance.

PMID- 16595697
TI  - Effects of dihydrotestosterone on skeletal muscle transcriptome in mice measured
      by serial analysis of gene expression.
AB  - In order to characterize the action of androgen in skeletal muscle, we have
      investigated the effects of castration (GDX) and dihydrotestosterone (DHT) on
      global gene expression in mice. The serial analysis of gene expression method was
      performed in the muscle of male mice in six experimental groups: intact, GDX and
      GDX+DHT injection 1, 3, 6 or 24 h before they were killed. A total of 780 822
      sequenced tags quantified the expression level of 80 142 tag species. Thirteen
      and seventy-nine transcripts were differentially expressed in GDX and DHT
      respectively (P < 0.05), including eight partially characterized and 21 potential
      novel transcripts. The induced transcripts within 3 h after DHT injection were
      involved in the following functions: transcription, protein synthesis,
      modification and degradation, muscle contraction and relaxation, cell signaling,
      polyamine biosynthesis, cell cycle progression and arrest, angiogenesis, energy
      metabolism and immunity. However, the inductions of transcripts related to cell
      cycle arrest and angiogenesis were no longer significant 24 h after DHT
      injection. The current study might suggest that DHT promotes protein synthesis,
      cell signaling, cell proliferation and ATP production, as well as muscle
      contraction and relaxation at the transcriptional level in skeletal muscle in
      vivo.

PMID- 16595699
TI  - Overexpression of the insulin-like growth factor I receptor in human
      pheochromocytomas.
AB  - In order to determine the role of the IGF-I receptor (IGF-IR) in human
      pheochromocytomas we have compared the expression of the IGF-IR in normal tissues
      and in pheochromocytomas with regard to the IGF-IR mRNA levels and ligand
      binding. By semiquantitative reverse transcription polymerase chain reaction (RT
      PCR), the mRNA of the IGF-IR could be detected in all samples of normal
      adrenomedullary cells (n = 13) and pheochromocytomas (n = 16). However,
      pheochromocytomas exhibited 2.8-fold higher mean IGF-IR mRNA levels than normal
      adrenomedullary cells (2.8 +/- 0.5 x 10(5) molecules/mug RNA vs 7.8 +/- 1.2 x
      10(5) molecules/mug RNA; P < 0.001). This overexpression of the IGF-IR in
      pheochromocytomas could be confirmed at the protein level by binding studies.
      Radioligand assays and Scatchard analysis revealed a single class of high
      affinity IGF-IR binding sites with a similar dissociation constant (Kd: 0.32 +/-
      0.1 nmol/l vs 0.22 +/- 0.08 nmol/l) for both normal adrenomedullary cells and
      pheochromocytomas. However, specific 125I-labeled IGF-I binding and the
      calculated receptor concentration were significantly elevated in
      pheochromocytomas as compared with normal adrenomedullary cells (58.3 +/- 5 vs
      24.3 +/- 12 nmol/kg protein; P < 0.05). In summary, our results demonstrate
      significant overexpression of the IGF-IR in human pheochromocytomas. This
      suggests a possible role of the IGF system in the pathogenesis of adrenal
      neoplasia and thus IGF-IR may be a target for future therapeutic approaches.

PMID- 16595698
TI  - CCAAT enhancer binding protein beta and hepatocyte nuclear factor 3beta are
      necessary and sufficient to mediate dexamethasone-induced up-regulation of
      alpha2HS-glycoprotein/fetuin-A gene expression.
AB  - Alpha2HS-glycoprotein/fetuin-A (Ahsg) is a serum protein preventing soft tissue
      calcification. In trauma and inflammation, Ahsg is down-regulated and therefore
      considered a negative acute phase protein. Enhancement of Ahsg expression as a
      protective serum protein is desirable in several diseases including tissue
      remodelling after trauma and infection, kidney and heart failure, and cancer.
      Using reporter gene assays in hepatoma cells combined with electrophoretic
      mobility shift assays we determined that dexamethasone up-regulates hepatic Ahsg.
      A steroid response unit at position -146/-119 within the mouse Ahsg promoter
      mediates the glucocorticoid-induced increase of Ahsg mRNA. It binds the
      hepatocyte nuclear factor 3beta and CCAAT enhancer binding protein beta (C/EBP
      beta). The up-regulation is mediated indirectly via glucocorticoid hormone
      induced transcriptional up-regulation in C/EBP-beta protein. A high degree of
      sequence identity in mouse, rat and human Ahsg promoters suggests that the
      promoter is similarly up-regulated by dexamethasone in all three species.
      Therefore, our findings suggest that glucocorticoids may be used to enhance the
      level of Ahsg protein circulating in serum.

PMID- 16595700
TI  - Glucose-induced repression of PPARalpha gene expression in pancreatic beta-cells
      involves PP2A activation and AMPK inactivation.
AB  - Tight regulation of fatty acid metabolism in pancreatic beta-cells is important
      for beta-cell viability and function. Chronic exposure to elevated concentrations
      of fatty acid is associated with beta-cell lipotoxicity. Glucose is known to
      repress fatty acid oxidation and hence to augment the toxicity of fatty acids.
      The peroxisome proliferator activated receptor alpha (PPARalpha) is a key
      activator of genes involved in beta-cell fatty acid oxidation, and transcription
      of the PPARalpha gene has been shown to be repressed by increasing concentrations
      of glucose in beta-cells. However, the mechanism underlying this transcriptional
      repression by glucose remains unclear. Here we report that glucose-induced
      repression of PPARalpha gene expression in INS-1E cells is independent of beta
      cell excitation and insulin secretion but requires activation of protein
      phosphatase 2A in a process involving inactivation of the AMP-activated protein
      kinase (AMPK). Pharmacological activation of AMPK at high glucose concentrations
      interferes with glucose repression of PPARalpha and PPARalpha target genes in INS
      1E cells as well as in rat islets. Specific knock-down of the catalytic AMPK
      subunit AMPKalpha2 but not AMPKalpha1 using RNAi suppressed PPARalpha expression,
      thereby mimicking the effect of glucose. These results indicate that activation
      of protein phosphatase 2A and subsequent inactivation of AMPK is necessary for
      glucose repression of PPARalpha expression in pancreatic beta-cells.

PMID- 16595701
TI  - Molecular cloning and regulation of porcine SULT2A1: relationship between SULT2A1
      expression and sulfoconjugation of androstenone.
AB  - Hydroxysteroid sulfotransferase (SULT2A1) is a key enzyme in the testicular and
      hepatic metabolism of 5alpha-androstenone, which is a major component of the off
      odor and off-flavor in pork known as boar taint. The goals of this study were to
      determine the role of testicular and hepatic SULT2A1 activity on plasma 5alpha
      androstenone sulfate levels, the accumulation of 5alpha-androstenone in adipose
      tissue, and to gain insight into the regulatory control of SULT2A1. Testicular
      SULT2A1 activity was negatively correlated (r = -0.57; P < 0.01) with 5alpha
      androstenone concentrations in fat. The differences observed in SULT2A1 activity
      warranted investigation into potential genetic variation within porcine SULT2A1.
      The cDNA sequence of porcine Sult2A1 was determined to be > 82% homologous to the
      human, mouse, and rat Sult2A1 genes. A single nucleotide polymorphism was
      detected within the coding region of the Sult2A1 from individual testes and liver
      samples; however, this did not affect the amino acid sequence of the enzyme.
      Western blot analysis determined that animals with high concentrations of 5alpha
      androstenone in fat and low SULT2A1 activity had corresponding low levels of
      SULT2A1 protein compared with animals with low levels of 5alpha-androstenone in
      fat. Real-time PCR analysis indicated that Sult2A1 mRNA was increased 2.8-fold in
      animals with high levels of the protein relative to animals with low levels of
      the protein. Furthermore, we demonstrated the positive role of the nuclear
      receptors constitutive androstane receptor and pregnane X receptor, as well as
      the possible role of farnesoid X receptor in the regulation of testicular SULT2A1
      activity. Together, the results of this study suggest that differences in SULT2A1
      expression can influence 5alpha-androstenone accumulation in fat.

PMID- 16595702
TI  - Identification and characterization of RanBPM, a novel coactivator of thyroid
      hormone receptors.
AB  - Thyroid hormone receptors (TRs) are transcription factor members of the nuclear
      receptor superfamily. The transcriptional activity of TRs is controlled by
      thyroid hormones and cell-specific coregulators. Using the yeast two-hybrid
      system, we identified RanBPM as a new protein partner for TRs. RanBPM was
      initially discovered as an interacting partner for Ran, and was also shown to be
      a protein partner and coactivator of the androgen receptor. The novel interaction
      between RanBPM and TR isoforms was addressed by glutathione-S-transferase (GST)
      pull-down assays and co-immunoprecipitation in intact mammalian cells, where
      RanBPM was shown to bind TRs in a ligand-independent fashion. We also studied the
      regions implicated in the interaction with deletion mutants: the principal
      interacting region of RanBPM is comprised within its carboxyl-terminal end and
      the TR DNA-binding domain is sufficient to mediate the interaction. To
      investigate the potential role of RanBPM in thyroid hormone action, transient
      transfections with luciferase reporter genes were performed in CV-1 cells. We
      found that the over-expression of RanBPM increases the activation of TRETK- and
      DR+4-positive thyroid hormone response elements. Interestingly, over-expression
      of the truncated protein RanBPM55, which lacks the N-terminal polyglutaminated
      region but binds TRs, decreased the fold activation by almost 80%. Furthermore,
      we performed competition assays using transient transfection of RanBPM and
      increasing amounts of RanBPM55. This revealed that the stimulating effect on TR
      transactivation by the full-length protein is inhibited in a dose-dependent
      fashion by RanBPM55. This suggests that although the polyglutaminated region of
      RanBPM is not required for the binding to TRs, it is required for the stimulation
      of TR transactivation. Taken together, our results provide evidence that RanBPM
      is a potent novel coactivator for thyroid hormone receptors.

PMID- 16595703
TI  - Induction of steroidogenesis in immature rat Leydig cells by interleukin-1alpha
      is dependent on extracellular signal-regulated kinases.
AB  - Interleukin-1alpha (IL-1alpha) plays an important role in the regulation of
      immune responses as well as in non-inflammatory events in different types of
      cells. Here we have investigated the involvement of the extracellular signal
      regulated kinase (ERK) cascade in IL-1alpha-induced steroidogenesis by primary
      cultures of immature rat Leydig cells. Our findings indicate that protein kinase
      C functions as an upstream component of signal transduction from the IL-1
      receptor type I (IL-1RI) to the ERK cascade. It was observed that IL-1alpha
      upregulated both steroidogenic acute regulatory (StAR) protein expression and its
      phosphorylation when compared with controls. Selective inhibition of these
      mitogen-activated protein kinases (MAPKs) by UO126 enhanced both the expression
      and phosphorylation of the StAR protein, but suppressed androgen production by
      the immature Leydig cells as well as dissipating the mitochondrial
      electrochemical potential (Psim) in these cells. The evidence that water-soluble
      cholesterol but not 22R-hydroxycholesterol-stimulated steroidogenesis was
      inhibited by UO126 suggested that an intact Psim across the inner mitochondrial
      membrane is required for cholesterol translocation and is positively regulated by
      the ERK cascade. We propose that activation of ERKs by IL-1alpha plays a dual
      role in the regulation of steroidogenesis in immature Leydig cells: these MAPKs
      downregulate StAR expression and phosphorylation, while at the same time they
      support an intact Psim across the inner mitochondrial membrane, thereby promoting
      translocation of cholesterol into the mitochondria of the Leydig cell.

PMID- 16595704
TI  - Zebrafish arylalkylamine-N-acetyltransferase genes - targets for regulation of
      the circadian clock.
AB  - Daily rhythms of melatonin production are controlled by changes in the activity
      of arylalkylamine-N-acetyltransferase (AANAT). Zebrafish possess two aanats,
      aanat1 and aanat2; the former is expressed only in the retina and the latter is
      expressed in both the retina and the pineal gland. Here, their differential
      expression and regulation were studied using transcript quantification and
      transient and stable in vivo and in vitro transfection assays. In the pineal
      gland, the aanat2 promoter exhibited circadian clock-controlled activity, as
      indicated by circadian rhythms of Enhanced green fluorescent protein (EGFP) mRNA
      in AANAT2:EGFP transgenic fish. In vivo transient expression analyses of the
      aanat2 promoter indicated that E-box and photoreceptor conserved elements (PCE)
      are required for expression in the pineal gland. In the retina, the expression of
      both genes was characterized by a robust circadian rhythm of their transcript
      levels. In constant darkness, the rhythmic expression of retinal aanat2 persisted
      while the aanat1 rhythm disappeared; indicating that the former is controlled by
      a circadian clock and the latter is also light driven. In the light-entrainable
      clock-containing PAC-2 zebrafish cell line, both stably transfected aanat1 and
      aanat2 promoters exhibited a clock-controlled circadian rhythm, characteristic
      for an E-box-driven expression. Transient co-transfection experiments in NIH-3T3
      cells revealed that the two, E-box- and PCE-containing, promoters are driven by
      the synergistic action of BMAL/CLOCK and orthehodenticle homeobox 5. This study
      has revealed a shared mechanism for the regulation of two related genes, yet
      describes their differential phases and photic responses which may be driven by
      other gene-specific regulatory mechanisms and tissue-specific transcription
      factor profiles.

PMID- 16595705
TI  - Direct electrochemistry of human, bovine and porcine cytochrome P450c17.
AB  - The direct electrochemistry of human, bovine and porcine cytochrome P450c17
      (CYP17) has been examined on an edge-oriented pyrolytic graphite electrode. The
      recombinant protein was immobilized on an electrode modified with a surfactant to
      simulate the environment of a biological membrane, and hence physiological
      electron-transfer conditions. The P450 enzymes all retained 'electron-transfer'
      activity while immobilized at the electrode surface as assessed by the presence
      of catalytic signals under aerobic conditions. The redox potentials for porcine
      P450c17 were more positive (anodic) than both the human and bovine forms, perhaps
      reflecting the differences in substrate specificity for these species. In
      addition, these enzymes were all influenced by pH, consistent with a single
      proton associated with the single electron-transfer event. Ionic strength of the
      buffer medium also shifted the redox potentials towards positive, suggesting that
      electrostatic forces contribute to the protein environment required for the
      electron-transfer process. The effect of substrate on the redox potential for
      each P450c17 was measured in the presence of pregnenolone, progesterone, 17alpha
      hydroxypregnenolone and 17alpha-hydroxyprogesterone. However, no influence on the
      redox parameters was observed.

PMID- 16595706
TI  - Human androgen receptor gene ligand-binding-domain mutations leading to disrupted
      interaction between the N- and C-terminal domains.
AB  - Most mutations in the androgen receptor (AR) ligand-binding domain (LBD) disrupt
      binding of the natural ligands: dihydrotestosterone and testosterone. Some AR LBD
      mutations do not affect ligand binding but they disrupt androgen-induced
      interaction of the N-terminal motif FXXLF and C-terminal activation function 2
      (AF2). As N-/C-terminal interaction requires binding of agonists that have
      androgen activity in vivo, it correlates well with the phenotype. To study this
      further, we searched the Cambridge intersex database for patients with a detected
      missense mutation in the AR LBD presenting with normal ligand binding. Six
      mutations (D695N, Y763C, R774H, Q798E, R855H and L907F) were selected and
      introduced by site-directed mutagenesis into the pSVAR and pM-LBD plasmids. The
      transactivational potential of the wild-type and mutant androgen receptors
      (pSVAR) was examined by dual-luciferase assay using pGRE-LUC as a reporter
      vector. N-/C-terminal interaction was studied by mammalian two-hybrid assay using
      wild-type and mutated AR LBD (pM-LBD), pVP16-rAR-(5-538) (encoding rat amino
      terminal AR) and pCMX-UAS-TK-LUC as a reporter. AR LBD mutations D695N, R774H and
      L907F presented with minimal transactivational capacity and N-/C-terminal
      interaction was totally disrupted. Mutations Y763C and R885H had some residual
      dose-dependent transactivational potential and minimal N-/C-terminal interaction.
      Q798E presented with good transactivational potential and it showed only mild
      reduction in N-/C-terminal interaction. With the selected mutations, N-/C
      terminal interaction correlated well with AR transactivation and the phenotype.
      Disrupted N-/C-terminal interaction is capable of providing the mechanism for
      androgen-insensitivity syndrome in most cases where the mutation in the LBD does
      not disrupt ligand binding. Furthermore, mutations leading to the disrupted N-/C
      terminal interaction can be localized to certain critical regions in the three
      dimensional structure of the AR LBD. Our study shows that apart from the
      previously reported regions, regions just before helix 3, between helices 5 and
      6, and at helix 10 are also important for AR N-/C-terminal interaction.

PMID- 16595707
TI  - Evaluation of denaturing high performance liquid chromatography for the
      mutational analysis of the MEN1 gene.
AB  - The identification of mutations in the MEN1 gene causing MEN1 has represented a
      challenge since the cloning of the gene in 1997 because of the lack of mutation
      hot-spots in the gene and the lack of phenotype-genotype correlations. The use of
      denaturing high performance liquid chromatography (DHPLC), a high throughput,
      reliable and automated heteroduplex-based technique, is the ideal for mutation
      detection in MEN1. In this work, DHPLC was optimised for the screening of the
      nine coding exons and splice junctions of MEN1. Thanks to collaboration between
      two French laboratories recognised as reference centres for genotypic MEN1
      diagnosis (Lyon and Lille), a blind retrospective study conducted in a cohort of
      160 unrelated MEN1 probands with (or without) known germline mutations was
      undertaken to evaluate the sensitivity of DHPLC. We were able to detect 101
      different sequence variations by DHPLC, distributed in the 10 analysed DNA
      fragments and corresponding to 100% of mutation detection compared with direct
      sequencing. 1.2% of samples were considered as false positive, exhibiting a
      heterogenous profile. DHPLC did not detect five cases of deletion or duplication
      of complete exons, neither did direct sequencing, showing the limits of the
      technique. Nevertheless, the method appeared to allow automated, rapid and low
      cost mutation detection with high accuracy. Direct sequencing can be then applied
      to identify the sequence variations on the targeted DNA fragments showing
      heterozygous profile by DHPLC. In conclusion, genotypic diagnosis of MEN1 can
      benefit from DHPLC in terms of efficacy, rapidity and cost.

PMID- 16595708
TI  - Angiotensin II stimulates the synthesis of vascular endothelial growth factor
      through the p38 mitogen activated protein kinase pathway in cultured mouse
      podocytes.
AB  - Angiotensin II (Ang-II) and vascular endothelial growth factor (VEGF) have an
      important role in the pathogenesis of diabetic nephropathy, but the signaling
      cascade of VEGF regulation in response to Ang-II in podocytes is largely unknown.
      In these experiments, we looked at the effect of Ang-II on the production of
      VEGF, and investigated whether VEGF production depends on the p38 mitogen
      activated protein kinase (MAPK) pathway in cultured mouse podocytes. Incubation
      of podocytes with Ang-II induced a rapid increase in VEGF mRNA expression and
      protein synthesis as well as its transcriptional activity in an Ang-II dose
      dependent manner. To further define the role of angiotensin type 1 (AT1) and type
      2 (AT2) receptors involved in Ang-II-mediated VEGF synthesis, the effects of
      selective AT1 and AT2 receptor antagonists were evaluated. Prior treatment with
      losartan significantly inhibited VEGF mRNA and protein synthesis induced by Ang
      II, which suggests that the AT1 receptor is involved in Ang-II-mediated VEGF
      synthesis. Furthermore, stimulation of the cells with Ang-II increased both
      phosphorylation of p38 MAPK and MAP kinase kinase 3/6 (MKK3/6). Additionally, Ang
      II enhanced the DNA binding activity to cAMP response element binding protein
      (CREB) and phosphorylation of CREB. In addition, to investigate the role of p38
      MAPK in Ang-II-induced VEGF synthesis, podocytes were pretreated with or without
      the p38 MAPK inhibitor, SB203580 for 24 h to observe whether Ang-II-mediated VEGF
      synthesis was inhibited by blocking p38 MAPK. The addition of SB203580 led to a
      marked inhibition of the increased VEGF mRNA and protein production induced by
      Ang-II in a dose-dependent manner. Taken together, these results suggest that Ang
      II stimulates the synthesis of VEGF in podocytes and the production of VEGF
      induced by Ang-II is mediated, in part, through the activation of the p38 MAPK
      pathway.

PMID- 16595709
TI  - The novel UGT1A9 intronic I399 polymorphism appears as a predictor of 7-ethyl-10
      hydroxycamptothecin glucuronidation levels in the liver.
AB  - Polymorphisms in UGT1A9 were associated with reduced toxicity and increased
      response to irinotecan in cancer patients. UDP-glucuronosyltransferase (UGT)
      protein expression, glucuronidation activities for 7-ethyl-10-hydroxycamptothecin
      (SN-38), and probe substrates of the UGT1A9 and UGT1A1 were measured in 48 human
      livers to clarify the role of UGT1A9 variants on the in vitro glucuronidation of
      SN-38. Genotypes were assessed for UGT1A9 (-2152C>T, -275T>A, and -118T(9>10)),
      three novel UGT1A9 variants (-5366G>T, -4549T>C, and I399C>T), and UGT1A1 (
      53TA(6>7), -3156G>A, and -3279T>G). Of all the variants, the UGT1A9 I399C>T was
      associated with the most dramatic change in SN-38-glucuronide (SN-38G) (2.64
      fold; p = 0.0007). Compared with UGT1A9 I399C/C, homozygous I399T/T presented
      elevated UGT1A1 and UGT1A9 proteins and higher glucuronidation of UGT1A9 and
      UGT1A1 substrates (p < 0.05). The very low linkage disequilibrium (r(2) < 0.19)
      between UGT1A9 I399 and all the other UGT1A1 and UGT1A9 variants suggests a
      direct effect or linkage to unknown functional variant(s) relevant to SN-38
      glucuronidation. The UGT1A9 -118T(9/10) was also linked to alteration of SN-38
      glucuronidation profiles in the liver (p < 0.05) and was associated with higher
      UGT1A1 protein (p = 0.03). However, UGT1A9 -118T(10) appears to have low
      functional impact as a result of the lack of correlation with UGT1A9 protein
      levels and a modest 1.4-fold higher reporter gene expression associated with the 
      118T(10) allele in HepG2 cells (p = 0.004). In contrast, the UGT1A9 -5366T, 
      4549C, -2152T, and -275A, associated with higher UGT1A9 protein (2-fold; p <
      0.05), have no influence on SN-38G. Despite limitations resulting from sample
      size, results indicate that UGT1A9 I399 and -118T(9/10) may represent additional
      candidates in combination with UGT1A1 promoter haplotypes for the prediction of
      SN-38 glucuronidation profile in vivo.

PMID- 16595710
TI  - Human UDP-glucuronosyltransferase, UGT1A8, glucuronidates dihydrotestosterone to
      a monoglucuronide and further to a structurally novel diglucuronide.
AB  - We identified human UDP-glucuronosyltransferase (UGT) isoforms responsible for
      producing dihydrotestosterone (DHT) diglucuronide, a novel glucuronide in which
      the second glucuronosyl moiety is attached at the C2' position of the first
      glucuronosyl moiety, leading to diglucuronosyl conjugation of a single hydroxyl
      group of DHT at the C17 position. Incubation of the DHT monoglucuronide with 12
      cDNA-expressed recombinant human UGT isoforms and uridine 5'-diphosphoglucuronic
      acid resulted in a low but measurable DHT diglucuronidation activity primarily
      with UGT1A8, a gastrointestinal UGT, and to a lesser extent with UGT1A1 and
      UGT1A9. In contrast, the activity of DHT monoglucuronidation was high and was
      found in UGT2B17, UGT2B15, UGT1A8, and UGT1A4 in descending order. Among the 12
      UGT isoforms tested, only UGT1A8 was capable of producing DHT diglucuronide from
      DHT. The kinetics of DHT diglucuronidation by microsomes from human liver and
      intestine fitted the Michaelis-Menten model, and the V(max)/K(m) value for the
      intestinal microsomes was approximately 4 times greater than that for the liver
      microsomes.

PMID- 16595711
TI  - Drug-drug interaction between pitavastatin and various drugs via OATP1B1.
AB  - It has already been demonstrated that pitavastatin, a novel potent HMG-coenzyme A
      reductase inhibitor, is taken up into human hepatocytes mainly by organic anion
      transporting polypeptide (OATP) 1B1. Because OATP2B1 is also localized in the
      basolateral membrane of human liver, we took two approaches to further confirm
      the minor contribution of OATP2B1 to the hepatic uptake of pitavastatin. Western
      blot analysis revealed that the ratio of the band density of OATP2B1 in human
      hepatocytes to that in our expression system is at least 6-fold lower compared
      with OATP1B1 and OATP1B3. The uptake of pitavastatin in human hepatocytes could
      be inhibited by both estrone-3-sulfate (OATP1B1/OATP2B1 inhibitor) and estradiol
      17beta-D-glucuronide (OATP1B1/OATP1B3 inhibitor). These results further supported
      the idea that OATP1B1 is a predominant transporter for the hepatic uptake of
      pitavastatin. Then, to explore the possibility of OATP1B1-mediated drug-drug
      interaction, we checked the inhibitory effects of various drugs on the
      pitavastatin uptake in OATP1B1-expressing cells and evaluated whether the in
      vitro inhibition was clinically significant or not. As we previously reported, we
      used the methodology for estimating the maximum unbound concentration of
      inhibitors at the inlet to the liver (I(u,in,max)). Judging from I(u,in,max) and
      inhibition constant (K(i)) for OATP1B1, several drugs (especially cyclosporin A,
      rifampicin, rifamycin SV, clarithromycin, and indinavir) have potentials for
      interacting with OATP1B1-mediated uptake of pitavastatin. The in vitro
      experiments could support the clinically observed drug-drug interaction between
      pitavastatin and cyclosporin A. These results suggest that we should pay
      attention to the concomitant use of some drugs with pitavastatin.

PMID- 16595712
TI  - Expression, purification, and characterization of mouse CYP2d22.
AB  - Metabolism of the prototype human CYP2D6 substrates debrisoquine and bufuralol
      proceeds at a much slower rate in mice; therefore, the mouse has been proposed as
      an animal model for the human CYP2D6 genetic deficiency. To interpret the
      molecular mechanism of this deficiency, a cDNA belonging to the CYP2D gene
      subfamily (Cyp2d22) has been cloned and sequenced from a mouse mammary tumor
      derived cell line. In the current study, Cyp2d22 enzyme was overexpressed and
      purified from insect cells using a baculovirus-mediated system. The activity of
      this purified enzyme was directly compared with purified human CYP2D6 toward
      codeine, dextromethorphan, and methadone as substrates. Purified Cyp2d22 was
      found to catalyze the O-demethylation of dextromethorphan with significantly
      higher K(m) values (250 microM) than that (4.2 microM) exhibited by purified
      human CYP2D6. The K(m) for dextromethorphan N-demethylation by Cyp2d22 was found
      to be 418 microM, much lower than that observed with human CYP2D6 and near the
      K(m) for dextromethorphan N-demethylation catalyzed by CYP3A4. CYP2D6 catalyzed
      codeine O-demethylation, whereas Cyp2d22 and CYP3A4 mediated codeine N
      demethylation. Furthermore, methadone, a known CYP3A4 substrate and CYP2D6
      inhibitor, was N-demethylated by Cyp2d22 with a K(m) of 517 microM and V(max) of
      4.9 pmol/pmol/min. Quinidine and ketoconazole, potent inhibitors to CYP2D6 and
      CYP3A4, respectively, did not show strong inhibition toward Cyp2d22-mediated
      dextromethorphan O- or N-demethylation. These results suggest that mouse Cyp2d22
      has its own substrate specificity beyond CYP2D6-like-deficient activity.

PMID- 16595714
TI  - Ectopic pregnancy in animals and humans.
AB  - Ectopic pregnancy denotes a pregnancy occurring elsewhere than in the cavity of
      the uterus. This pathology has been recognised for years and it causes numerous
      maternal deaths during the first trimester of pregnancy. While this condition is
      well-known in humans, it is rarely diagnosed in animals. However, the causes and
      mechanisms leading to an ectopic implantation of the ovum are not always clearly
      defined in humans or animals. Two types of ectopic pregnancy are mainly
      recognized: (1) tubal pregnancy occurs when an oocyte is fertilized and then
      remains in the oviduct and (2) abdominal pregnancy occurs when the gestation
      develops in the peritoneal cavity. The latter may be subdivided into two
      subtypes: the primary form, when a fertilized oocyte enters the peritoneal cavity
      and becomes attached to the mesentery or abdominal viscera, and the secondary
      form, which follows the rupture of an oviduct or the uterus after the fetus has
      been implanted, and the fetus is expelled into the peritoneal cavity. Cornual,
      ovarian and cervical ectopic locations are less frequent. Several differences
      exist in ectopic pregnancies between human beings and animal species. While
      abdominal pregnancy has been described in both human and animal species, tubal
      ectopic pregnancies would appear to be restricted to primates. Other than
      anecdotal cases, this pathological condition does not occur in laboratory,
      domestic or farm animals. Several factors are described as being the cause of
      these differences.

PMID- 16595713
TI  - Regulation of the neuroendocrine reproductive axis by kisspeptin-GPR54 signaling.
AB  - The Kiss1 gene codes for a family of peptides that act as endogenous ligands for
      the G protein-coupled receptor GPR54. Spontaneous mutations or targeted deletions
      of GPR54 in man and mice produce hypogonadotropic hypogonadism and infertility.
      Centrally administered kisspeptins stimulate gonadotropin secretion by acting
      directly on GnRH neurons. Sex steroids regulate the expression of KiSS-1 mRNA in
      the brain through direct action on KiSS-1 neurons. In the arcuate nucleus (Arc),
      sex steroids inhibit the expression of KiSS-1, suggesting that these neurons
      serve as a conduit for the negative feedback regulation of gonadotropin
      secretion. In the anteroventral periventricular nucleus (AVPV), sex steroids
      induce the expression of KiSS-1, implying that KiSS-1 neurons in this region may
      have a role in the preovulatory LH surge (in the female) or sexual behavior (in
      the male).

PMID- 16595715
TI  - Kit ligand and c-Kit are expressed during early human ovarian follicular
      development and their interaction is required for the survival of follicles in
      long-term culture.
AB  - The receptor tyrosine c-Kit and its cognate ligand, c-Kit ligand (KL, stem cell
      factor, SCF), are involved in ovarian follicular development in several animal
      species. We studied the expression of KL and c-Kit using in situ hybridization
      and immunohistochemistry in donated human ovarian cortical tissue. The KL
      transcripts were expressed in granulosa cells of primary follicles, whereas the
      expression of c-Kit was confined to the oocyte and granulosa cells in primary and
      secondary follicles. We employed an ovarian organ culture using firstly serum
      containing and then serum-free medium to study the effects of KL and an anti-c
      Kit antibody, ACK2, on the development and survival of ovarian follicles in
      vitro. Culture of ovarian cortical slices for 7 days resulted in a 37% increase
      in the number of primary follicles and a 6% increase in secondary follicles. The
      proportion of viable follicles decreased in all cultures. The addition of KL (1,
      10 and 100 ng/ml) into the culture media did not affect the developmental stages
      of the follicles or the proportion of atretic follicles. Inclusion of ACK2 (800
      ng/ml) in the culture medium significantly increased the proportion of atretic
      follicles on days 7 (49 vs 28% in control cultures) and 14 (62 vs 38%) of
      culture. In conclusion, c-Kit and KL are expressed in human ovaries during
      follicular development. Blocking the c-Kit receptor induces follicular atresia.
      The KL/c-Kit signaling system is likely to control the survival of human ovarian
      follicles during early follicular development.

PMID- 16595716
TI  - Suppressed expression of genes involved in transcription and translation in in
      vitro compared with in vivo cultured bovine embryos.
AB  - In vivo-derived bovine embryos are of higher quality than those derived in vitro.
      Many of the differences in quality can be related to culture environment-induced
      changes in mRNA abundance. The aim of this study was to identify a range of mRNA
      transcripts that are differentially expressed between bovine blastocysts derived
      from in vitro versus in vivo culture. Microarray (BOTL5) comparison between in
      vivo- and in vitro-cultured bovine blastocysts identified 384 genes and expressed
      sequence tags (ESTs) that were differentially expressed; 85% of these were down
      regulated in in vitro cultured blastocysts, showing a much reduced overall level
      of mRNA expression in in vitro- compared with in vivo-cultured blastocysts.
      Relative expression of 16 out of 23 (70%) differentially expressed genes
      (according to P value) were verified in new pools of in vivo- and in vitro
      cultured blastocysts, using quantitative real-time PCR. Most (10 out of 16) are
      involved in transcription and translation events, suggesting that the reason why
      in vitro-derived embryos are of inferior quality compared with in vivo-derived
      embryos is due to a deficiency of the machinery associated with transcription and
      translation.

PMID- 16595717
TI  - Centrosome changes during meiosis in horse oocytes and first embryonic cell cycle
      organization following parthenogenesis, fertilization and nuclear transfer.
AB  - Various types of cell cycle organization occur in mammals. In this study,
      centrosome changes during meiosis in horse oocytes, and first cell cycle
      organization following fertilization, parthenogenesis and nuclear transfer, were
      monitored. Cumulus oocyte complexes harvested from horse ovaries obtained from
      slaughtered mares were cultured in vitro. Meiotic oocytes of germinal vesicle
      (GV), germinal vesicle breakdown (GVBD), metaphase I and II (MI and MII) stages
      were selected at various set times during in vitro maturation. Embryos at the
      first cell cycle stage were generated by subjecting MII stage oocytes to
      fertilization by intracytoplasmic sperm injection (ICSI), parthenogenetic
      treatment or nuclear transfer. Centrosome changes during meiosis and the first
      cell cycle organization were detected by indirect immunofluorescent staining,
      using a mouse anti-alpha-tubulin antibody for microtubules and a rabbit anti
      gamma-tubulin antibody for centrosomes. These examinations showed that the
      centrosomes of the horse oocyte reorganize themselves from the beginning of GV
      stage to leave only PCM of gamma-tubulin surrounding both poles of the MI and MII
      stage spindles. These MII oocytes can organize the separation of metaphase
      chromosomes during the first embryonic cell cycle by parthenogenetic treatment.
      When the MII oocytes were subjected to ICSI or nuclear transfer, one or two red
      stained centrosomes of gamma-tubulin were introduced by the fertilising
      spermatozoon or the donor cell which associated with the sperm chromatin in the
      fertilized embryos and with the donor cell chromatin and microtubules in the
      cloned embryos. This finding suggests that centrosomes are not an essential
      component in the formation of the metaphase spindle during meiotic maturation of
      horse oocytes, but they can be introduced from the spermatozoon or donor cell and
      are necessary for the organization of normal embryonic development.

PMID- 16595718
TI  - Reciprocal expression of 17alpha-hydroxylase-C17,20-lyase and aromatase
      cytochrome P450 during bovine trophoblast differentiation: a two-cell system
      drives placental oestrogen synthesis.
AB  - No definitive information is yet available on the steroidogenic capacity of the
      two morphologically distinct cell types forming the bovine trophoblast, the
      uninucleated trophoblast cells (UTCs) and the trophoblast giant cells (TGCs).
      Hence, in order to localise 17alpha-hydroxylase-C17,20-lyase (P450c17) on a
      cellular level and to monitor its expression as a function of gestational age,
      placentomes from pregnant (days 80-284; n = 19), prepartal (days 273-282; 24-36 h
      prior to the onset of labour; n = 3) and parturient cows (n = 5) were
      immunostained for P450c17 using an antiserum against the recombinant bovine
      enzyme. At all stages investigated, P450c17 was exclusively found in the UTCs of
      chorionic villi (CV), where staining was ubiquitous between days 80 and 160, but
      was largely restricted to primary CV and the branching sites of secondary CV
      between days 160 and 240. Thereafter, a distinct ubiquitous staining reoccurred
      in the UTCs of all CV in late pregnant, prepartal and parturient animals. Using
      an antiserum against human aromatase cytochrome P450 (P450arom), specific
      cytoplasmic staining was observed in TGCs. In placentomes from pregnant cows,
      staining intensity was higher in mature compared with immature TGCs and was more
      pronounced in the trophoblast covering big stem villi compared with the
      trophoblast at other sites of the villous tree. In placentomes of a parturient
      cow, specific staining was only found in mature TGCs that survived the normal,
      but substantial, prepartal decline in TGC numbers. These results clearly showed
      that bovine UTCs and TGCs exhibit different steroidogenic capacities,
      constituting a 'two-cell' organisation for oestrogen synthesis. P450c17
      expression appears to be quickly down-regulated and P450arom is up-regulated when
      UTCs enter the TGC differentiation pathway.

PMID- 16595719
TI  - Fertility of mice receiving vitrified adult mouse ovaries.
AB  - Cryopreservation of the ovaries is a useful technology for preservation of germ
      cells from experimental animals, because if the female founder is infertile or
      has mutated mitochondrial DNA, preservation of female germ cells is necessary.
      Although it is possible to cryopreserve immature mouse ovaries with a high degree
      of viability by vitrification with a mixture of several cryoprotectants, the
      viability of cryopreserved adult mouse ovaries is still unknown. Here, we
      investigated the viability of mouse ovaries at various ages after
      cryopreservation by vitrification techniques. Donor ovaries were collected from
      10-day-, 4-week-, 10-week- and 7-month-old, female, nulliparous, green
      fluorescence protein (GFP)-transgenic mice and cryopreserved by vitrification.
      The vitrified-warmed ovaries were orthotopically transplanted to 4- or 10-week
      old mice. GFP-positive pups were obtained in all experimental groups. In the 4
      week-old recipients, the percentages of GFP-positive pups among the total pups
      from recipients transplanted with ovaries of 10-day-, 4-week-, 10-week- and 7
      month-old donors were 44%, 9%, 12% and 4% respectively. In the 10-week-old
      recipients, the percentages of GFP-positive pups among the total pups from
      recipients transplanted with ovaries of 10-day-, 4-week-, 10-week- and 7-month
      old donors were 36%, 16%, 2% and 9% respectively. Furthermore, GFP-positive pups
      also were obtained from recipients transplanted with ovaries of donors without
      normal estrous cyclicity. Our results indicate that cryopreservation of mouse
      ovaries by vitrification is a useful method for the preservation of female germ
      cells from mice of various ages.

PMID- 16595720
TI  - Presence and regulation of messenger ribonucleic acids encoding components of the
      class II major histocompatibility complex-associated antigen processing pathway
      in the bovine corpus luteum.
AB  - Luteal cells express class II major histocompatibility complex (MHC) molecules
      and can stimulate T lymphocyte proliferation in vitro. However, it is unknown
      whether luteal cells express the intracellular components necessary to process
      the peptides presented by class II MHC molecules. The objective of the present
      study was to examine the expression and regulation of three major class II
      associated antigen processing components--class II MHC-associated invariant chain
      (Ii), DMalpha and DMbeta--in luteal tissue. Corpora lutea were collected early in
      the estrous cycle, during midcycle and late in the estrous cycle, and at various
      times following administration of a luteolytic dose of prostaglandin F(2alpha)
      (PGF(2alpha)) to the cow. Northern analysis revealed the presence of mRNA
      encoding each of the class II MHC-associated antigen processing proteins in
      luteal tissue. Ii mRNA concentrations did not change during the estrous cycle,
      whereas DMalpha and DMbeta mRNA concentrations were highest in midcycle luteal
      tissue compared with either early or late luteal tissue. Tumor necrosis factor
      alpha (TNF-alpha) reduced DMalpha mRNA concentrations in cultured luteal cells in
      the presence of LH or PGF(2alpha). DMalpha and DMbeta mRNA were also present in
      highly enriched cultures of luteal endothelial (CLENDO) cells, and DMalpha mRNA
      concentrations were greater in CLENDO cultures compared with mixed luteal cell
      cultures. Expression of invariant chain, DMalpha and DMbeta genes indicates that
      cells within the corpus luteum express the minimal requirements to act as
      functional antigen-presenting cells, and the observation that CLENDO cells are a
      source of DMalpha and DMbeta mRNA indicates that non-immune cells within the
      corpus luteum may function as antigen-presenting cells.

PMID- 16595721
TI  - Relationships of changes in B-mode echotexture and colour-Doppler signals in the
      wall of the preovulatory follicle to changes in systemic oestradiol
      concentrations and the effects of human chorionic gonadotrophin in mares.
AB  - A duplex grey-scale and colour-Doppler ultrasound instrument was used to study
      the changes in the wall of the preovulatory follicle in mares. When the follicle
      reached > or =35 mm (hour 0), mares were randomized into control (n = 16) and
      human chorionic gonadotropin (hCG)-treated (n = 16) groups. The hCG treatment was
      given at hour 0. Scanning was done every 12 h until hour 36, every hour between
      hours 36 and 48, and every 12 h thereafter until ovulation. Blood was sampled
      every 12 h for oestradiol assay. During the period 0-24 h post-treatment,
      oestradiol concentrations decreased in the hCG group and increased in the
      controls (significant interaction). During the period 0-36 h post-treatment,
      thickness and echogenicity of the granulosa increased in the hCG group but not in
      the controls. During the period 36 to 12 h before ovulation, granulosa and colour
      Doppler end-points increased in the control and hCG groups (hour effects), while
      oestradiol was decreasing in both groups. The prominence and percentage of
      follicle circumference with an anechoic band peripheral to the granulosa and
      colour-Doppler signals in the follicle wall, indicating arterial blood flow,
      decreased during the period 4 to 1 h before ovulation (hour effects). Results
      indicated that the ultrasonographic changes of the wall of the preovulatory
      follicle were not associated temporally with changes in oestradiol concentrations
      and prominence of an anechoic band, and colour-Doppler signals decreased during
      the few hours before ovulation. The hypothesis that the latter portion of the
      ovulatory LH surge has a negative effect on systemic oestradiol was supported by
      the immediate decrease in oestradiol concentrations when hCG was injected.

PMID- 16595722
TI  - Selective expression of the scaffold protein JSAP1 in spermatogonia and
      spermatocytes.
AB  - Scaffold proteins of mitogen-activated protein kinase (MAPK) intracellular signal
      transduction pathways mediate the efficient and specific activation of the
      relevant MAPK signaling modules. Previously, our group and others have identified
      c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated
      protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffold protein
      for JNK MAPK pathways. Although JSAP1 is expressed in the testis in adults, its
      expression during development has not been investigated. In addition, it is
      unknown which types of cells in the testis express the scaffold protein. Here, we
      examined the expression of JSAP1 in the testis of mice aged 14 days, 20 days, 6
      weeks, and 12 weeks by immunohistochemistry and Western blotting. The specificity
      of the anti-JSAP1 antibody was evaluated from its reactivity to exogenously
      expressed JSAP1 and a structurally related protein, and by antigen-absorption
      experiments. The immunohistochemical analyses with the specific antibody showed
      that the JSAP1 protein was selectively expressed in the spermatogonia and
      spermatocytes, but not in other cell types, including spermatids and somatic
      cells, during development. However, not all spermatogonia and spermatocytes were
      immunopositive either, especially in the 12-week-old mouse testis. Furthermore,
      we found by Western blotting that the expression levels of JSAP1 protein vary
      during development; there is high expression until 6 weeks after birth, which
      approximately corresponds to the end of the first wave of spermatogenesis.
      Collectively, these results suggest that JSAP1 function may be important in
      spermatogenic cells during early postnatal development.

PMID- 16595723
TI  - Mouse pregnancy-specific glycoproteins: tissue-specific expression and evidence
      of association with maternal vasculature.
AB  - The pregnancy-specific glycoproteins (Psg) are secreted hormones encoded by
      multiple genes in rodents and primates, and are thought to act as immune
      modulators. The only Psg receptor identified is CD9, through which Psg17 induces
      cytokine production from macrophages cultured in vitro. We examined temporal and
      spatial aspects of Psg and CD9 expression during mouse pregnancy to determine
      whether their expression patterns support a role in immune modulation. Using in
      situ hybridisation, immunohistochemistry and RT-PCR we found Psg expression in
      trophoblast giant cells and in the spongiotrophoblast. Psg22 is the predominant
      Psg family member expressed in giant cells. Detectable Psg is associated
      predominantly with endothelial cells lining vascular channels in the decidua,
      rather than with maternal immune cell markers. CD9 expression exhibited partial
      overlap with Psg, but without exclusive co-localisation. CD9 was observed in
      decidual cells surrounding early implantation sites, and in the endometrium.
      However, embryo transfer of wild-type embryos to CD9-deficient females indicates
      that maternal CD9 is not essential for successful pregnancy.

PMID- 16595724
TI  - The effects of sex steroid hormones and interleukin-1-beta on MUC1 expression in
      endometrial epithelial cell lines.
AB  - Oestrogen, progesterone and paracrine signals from the embryo have been
      associated with the overall control of implantation. Changes in the expression of
      the heavily glycosylated transmembrane glycoprotein MUC1 mucin on the endometrial
      epithelium are also thought to be important for embryo attachment. Increased MUC1
      expression has been correlated with elevated progesterone levels in the secretory
      phase of the menstrual cycle. Embryonic control of endometrial receptivity
      through changes in MUC1 expression could be achieved through the interleukin-1
      system. Four endometrial epithelial cell lines (HEC1A, HEC1B, Ishikawa and RL592)
      were treated with oestrogen and progesterone (with or without interleukin-1-beta)
      and were subjected to immunocytochemistry and flow cytometric analysis to
      determine MUC1 production using MUC1 antibodies. HEC1A (oestrogen receptor (ER)
      and progesterone receptor (PR) positive) and HEC1B (ER positive and PR negative)
      were transfected with the MUC1 promoter, underwent similar treatment regimes and
      the activity of the MUC1 promoter relative to their untreated controls was
      determined using a chloramphenicol acetyltransferase (CAT) enzyme-linked
      immunoassay. Using the cell lines, we determined that endometrial MUC1 expression
      is up-regulated by progesterone, consistent with the in vivo increases in MUC1
      related to high progesterone levels. We also revealed that neither oestrogen, nor
      interleukin-1-beta, appear to modulate MUC1. Progesterone-dependent regulation of
      MUC1 is likely to be an important factor in determining endometrial receptivity.

PMID- 16595725
TI  - Localization and steroid regulation of prostaglandin E2 receptor protein
      expression in ovine cervix.
AB  - Although prostaglandin E2 (PGE2) has been identified as a central mediator of the
      cervical ripening process, the mechanisms responsible for PGE2 ripening are still
      poorly understood, partly because of the lack of information concerning the
      precise cellular localization and regulation of PGE2 (EP) receptors in the
      cervix. To provide new insights into the mechanisms of cervical ripening, we used
      indirect immunofluorescence to localize cervical EP receptor protein expression
      in ovariectomized ewes and examined the effect of administration of progesterone
      or estradiol. EP receptors were widely distributed in cervical blood vessels,
      epithelium of the cervical canal, circular and longitudinal muscles, and stroma.
      Estradiol replacement decreased EP1 and EP3 receptor protein in blood vessel
      media (by 23 and 31% respectively, P < 0.05) and decreased EP1 receptor protein
      expression in the longitudinal muscle layer (by 27%, P < 0.05). Stromal EP1 and
      EP3 receptor protein expression was also reduced by estradiol (by 29 and 20%
      respectively, P < 0.05). Progesterone replacement had no significant effect on EP
      receptor protein expression. The arterial changes would favor PGE2-induced
      vasodilatation, subsequent edema and leukocyte infiltration during the cervical
      ripening process whereas the muscular alterations would facilitate smooth muscle
      relaxation and cervical dilatation. Furthermore, estradiol provoked perinuclear
      localization of EP3 receptor protein in the longitudinal muscle layer. This
      latter result suggests that cellular EP receptor localization is regulated by
      estradiol and that PGE2 may also control smooth muscle contraction and regulate
      ovine cervical dilatation in an intracrine manner via EP3 receptors.

PMID- 16595726
TI  - Glycosylation dependent cell adhesion molecule 1-like protein and L-selectin
      expression in sheep interplacentomal and placentomal endometrium.
AB  - Glycosylation dependent cell adhesion molecule 1 (GlyCAM-1), a mucin component of
      sheep histotroph produced by glandular epithelium (GE) during early pregnancy, is
      hypothesized to function in implantation. However, GlyCAM-1 is present in uterine
      tissues subsequent to implantation suggesting additional functions of this l
      selectin-binding ligand. This study focused on uterine GlyCAM-1 expression during
      placentome development in sheep. Western blot analysis of day 50 pregnant sheep
      identified 45, 40, and 25 kDa bands in interplacentomal endometrium, 40 and 25
      kDa bands in placentomes, and 80 and 40 kDa bands in chorioallantois. The GlyCAM
      1 proteins in interplacentomal regions were comparable to those detected in day
      15-19 pregnant sheep, however, the 80 kDa form was unique to chorioallantois, and
      the absence of the 45 kDa GlyCAM-1 in placentomes indicated differences between
      interplacentomal and placentomal endometrium. Immunofluorescence identified
      GlyCAM-1 in lumenal epithelium (LE), stromal fibroblasts, and vascular smooth
      muscle cells. To better define its cellular distribution, GlyCAM-1 was co
      localized with either epithelium-specific cytokeratin, smooth muscle-specific
      alpha-smooth muscle actin (alpha SMA), or stromal-specific vimentin. In
      interplacentomal endometrium, GlyCAM-1 co-localized with cytokeratin in LE but
      not in GE. GlyCAM-1 did not co-localize with alpha SMA, and was localized in the
      extracellular matrix of vimentin-positive stroma. In placentomes, GlyCAM-1 did
      not co-localize with cytokeratin, but did co-localize with alpha SMA and
      vimentin. Thus, in contrast to interplacentomal regions, GlyCAM-1 in placentomes
      was predominantly localized in vasculature rather than epithelial cells. Further,
      leukocytes expressing L-selectin were localized to the endothelial surface of
      GlyCAM-1-expressing vessels within placentomes. These data suggest that GlyCAM-1
      assumes distinct functions in compartment-specific regions of the sheep uterus.

PMID- 16595727
TI  - Estradiol and its membrane-impermeable conjugate estradiol-BSA inhibit tamoxifen
      stimulated prolactin secretion in incubated rat pituitaries.
AB  - In the absence of estrogen (E), the selective E receptor modulator tamoxifen (TX)
      has two agonist effects in the rat pituitary: induction of progesterone receptor
      (PR)-dependent GnRH self-priming in the gonadotrope, and stimulation of prolactin
      (PRL) secretion in the lactotrope. TX-induced gonadotropin (GnRH) self-priming is
      absent when 10(-8) M estradiol-17beta (E2) is added to the incubation medium of
      pituitaries from TX-treated rats. The present experiments investigated whether PR
      independent PRL release into the incubation medium of pituitaries from TX-treated
      ovariectomized (OVX) rats was affected by E2, and the effect of different ER
      ligands (ICI182780, TX, estradiol-17alpha, E2 -BSA) on TX-stimulated PRL
      secretion. Moreover, the effect of E2 on TRH-stimulated PRL secretion in
      pituitaries collected from estradiol benzoate- and TX-treated OVX rats was
      studied. It was found that: i) incubation with E2 supressed the PRL releasing
      effect of injected TX; ii) whereas coincubation with the pure anti-E type II
      ICI182780 antagonized the inhibitory effect of E2, coincubation with the anti-E
      type I TX did not; iii) estradiol-17alpha lacked inhibitory action, whereas a
      dose-dependent inhibitory effect of both E2 and E2 -BSA was noticed; and iv) TRH
      stimulatory effect on PRL release in pituitaries from TX-treated rats was blocked
      by addition of E2 to the medium. Taken together, these data argue in favor of the
      presence of specific membrane recognition sites for E in the lactotrope involved
      in steroid-specific E2 inhibition of TX-stimulated PRL secretion.

PMID- 16595728
TI  - Short photoperiod-induced ovarian regression is mediated by apoptosis in Siberian
      hamsters (Phodopus sungorus).
AB  - Siberian hamster reproduction is mediated by photoperiod-induced changes in
      gonadal activity. However, little is known about how photoperiod induces cellular
      changes in ovarian function. We hypothesized that exposing female hamsters to
      short (inhibitory) as opposed to long (control) photoperiods would induce an
      apoptosis-mediated disruption of ovarian function. Ovaries and plasma from
      hamsters exposed to either long (LD, 16 h light:8 h darkness) or short (SD, 8 h
      light:16 h darkness) days were collected during diestrus II after 3, 6, 9 and 12
      weeks and processed for histology or RIA respectively. Apoptosis was assessed by
      in situ TUNEL and active caspase-3 protein immunolabeling. No significant
      differences were observed among LD hamsters for any parameter; therefore, these
      control data were pooled. SD exposure induced a decline in preantral follicles (P
      < 0.05), early antral/antral follicles (P < 0.01) and corpora lutea (P < 0.01) by
      week 12 as compared with LD. Terminal atretic follicles appeared by SD week 9; by
      week 12, these had become the predominant ovarian structures. Estradiol
      concentrations decreased by weeks 9 and 12 SD when compared with both LD and week
      3 SD hamsters (P < 0.05); however, no changes were observed for progesterone.
      TUNEL-positive follicles in SD ovaries increased at week 3 and subsequently
      declined by week 12 as compared with LD ovaries (P < 0.01). Active capsase-3
      protein immunostaining peaked at SD week 3 as compared with all other groups (P <
      0.01). TUNEL and capsase-3 immunolabeling were localized to granulosa cells of
      late-preantral and early-antral/antral follicles. These data indicate that SD
      exposure rapidly induces follicular apoptosis in Siberian hamsters, which
      ultimately disrupts both estradiol secretion and folliculogenesis, resulting in
      the seasonal loss of ovarian function.

PMID- 16595729
TI  - Reduction of body-weight gain enhances in vitro embryo production in overfed
      superovulated dairy heifers.
AB  - The aim of our study was to test whether a reduction in dietary intake could
      improve in vitro embryo production in superovulated overfed dairy heifers.
      Cumulus-oocyte complexes of 16 Prim' Holstein heifers (14 +/- 1 months old) were
      collected by ovum pick-up (OPU), every 2 weeks following superovulation treatment
      with 250 microg FSH, before being matured and fertilized in vitro. Embryos were
      cultured in Synthetic Oviduct Fluid medium for 7 days. Heifers were fed with hay,
      soybean meal, barley, minerals and vitamins. From OPU 1 to 4 (period 1), all
      heifers received individually for 8 weeks a diet formulated for a 1000 g/day live
      weight gain. From OPU 5 to 8 (period 2), the heifers were allocated to one of two
      diets (1000 or 600 g/day) for 8 weeks. Heifers' growth rates were monitored and
      plasma concentrations of metabolites, metabolic and reproductive hormones were
      measured each week. Mean live-weight gain observed during period 1 was 950 +/- 80
      g/day (n = 16). In period 2 it was 730 +/- 70 (n = 8) and 1300 +/- 70 g/day (n =
      8) for restricted and overfed groups respectively. When comparing period 1 and
      period 2 within groups, significant differences were found. In the restricted
      group, a higher blastocyst rate, greater proportions of grade 1-3 and grade 1
      embryos, associated with higher estradiol at OPU and lower glucose and beta
      hydroxybutyrate, were observed in period 2 compared with period 1. Moreover,
      after 6 weeks of dietary restriction (OPU 7), numbers of day 7 total embryos,
      blastocysts and grade 1-3 embryos had significantly increased. On the contrary,
      in the overfed group, we observed more <8 mm follicles 2 days before
      superovulation treatment, higher insulin and IGF-I and lower nonesterified fatty
      acids in period 2 compared with period 1 (no significant difference between
      periods for embryo production). After 6 weeks of 1300 g/day live-weight gain (OPU
      7), embryo production began to decrease. Whatever the group, oocyte collection
      did not differ between period 1 and 2. These data suggest that following a period
      of overfeeding, a short-term dietary intake restriction (6 weeks in our study)
      may improve blastocyst production and embryo quality when they are low. However,
      nutritional recommendations aiming to optimize both follicular growth and
      embryonic development may be different.

PMID- 16595730
TI  - Improved development by Taxol pretreatment after vitrification of in vitro
      matured porcine oocytes.
AB  - This study was designed to examine the effect of Taxol pretreatment on
      vitrification of porcine oocytes matured in vitro by an open pulled straw (OPS)
      method. In the first experiment, the effect of Taxol pretreatment and fluorescein
      diacetate (FDA) staining on parthenogenetic development of oocytes was evaluated.
      In the second experiment, viability, microtubule organization and embryo
      development of oocytes were assessed after oocytes were exposed to
      vitrification/warming solutions or after vitrification with or without Taxol
      pretreatment. The results showed that Taxol pretreatment and/or FDA staining did
      not negatively influence the oocyte's developmental competence after
      parthenogenetic activation. After being exposed to vitrification/warming
      solutions, the survival rate (83.3%) of the oocytes was significantly (P < 0.05)
      reduced as compared with that in the control (100%). Vitrification/warming
      procedures further reduced the survival rates of oocytes regardless of oocytes
      being treated with (62.1%) or without (53.8%) Taxol. The proportions of oocytes
      with normal spindle configuration were significantly reduced after the oocytes
      were exposed to vitrification/warming solutions (38.5%) or after vitrification
      with (10.3%) or without (4.1%) Taxol pretreatment as compared with that in
      control (76.8%). The rates of two-cell-stage (5.6-53.2%) embryos at 48 h and
      blastocysts (0-3.8%) at 144 h after activation were significantly reduced after
      exposure to vitrification/warming solutions or after vitrification as compared
      with control (90.9% and 26.6% respectively). However, the proportion of vitrified
      oocytes developed to two-cell stage was significantly higher when oocytes were
      pretreated with (24.3%) than without (5.6%) Taxol. These results indicate that
      pretreatment of oocytes with Taxol before vitrification helps to reduce the
      damage induced by vitrification and is a potential way to improve the development
      of vitrified porcine oocytes.

PMID- 16595731
TI  - Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits
      following developmental exposure to vinclozolin, a fungicide.
AB  - We studied sequelae of prenatal plus infantile exposure of male rabbits to
      vinclozolin, because it is ingested by women and children. Female Dutch-Belted
      rabbits (7-10/group) were treated daily per orum from gestation day 15 through
      post-natal week 4 to provide 0, 7.2, or 72 mg vinclozolin/kg dam's body
      weight/day. Vinclozolin had no effect on maintenance of pregnancy, growth of
      pups, age at testicular descent or weight of organs. Concentrations of serum LH
      or testosterone at 6, 12, or 24 weeks of age were unaffected. However, FSH was
      lower (P < 0.05) in both vinclozolin groups at all three ages. Following
      injection of GnRH at 12 or 24 weeks, the increase in FSH was less (P < 0.05) in
      both vinclozolin groups, as was testosterone at 12 weeks of age. After full
      sexual maturity, 2 of 7 low dose rabbits were uninterested in female or male
      teasers and never achieved erection or ejaculation. Overall, rates of ejaculation
      failure were: control 0% (0/48), low dose 29% (12/42), and high dose 5% (3/60).
      Daily sperm production per gram of testis and total number of sperm per ejaculate
      in both vinclozolin groups were similar (P > 0.1) to controls. However, semen
      from vinclozolin rabbits contained over two times more (P < 0.05) morphologically
      abnormal spermatozoa, mostly nuclear and acrosomal defects, than semen from
      controls. Seminiferous tubules with degenerative changes were more frequent (P <
      0.05) in vinclozolin rabbits than in controls. Lesions included syncytia of
      spherical spermatids and desquamation of germ cells. Hence, developmental
      exposure to vinclozolin caused presumably permanent changes in copulatory
      ability, secretion of FSH, and spermiogenesis.

PMID- 16595732
TI  - A case-control study on the association of idiopathic recurrent pregnancy loss
      with autoantibodies against beta2-glycoprotein I and annexin V.
AB  - Whereas antiphospholipid antibodies (aPL) are associated with thrombotic events
      and recurrent spontaneous abortion (RSA), the contribution of anti-beta2
      glycoprotein 1 (beta2GP1) and anti-annexin V antibodies as risk factors for RSA
      remain poorly understood. We investigated anti-beta2-GPI and anti-annexin V IgM
      and IgG antibodies as potential risk factors for RSA in 200 women with more than
      three consecutive idiopathic RSA, and 200 age-matched, healthy, parous women.
      Pearson's chi squared test analysis showed that while anti-beta2-GPI IgG (P =
      0.416) and IgM (P = 0.72) were comparable between patients and controls, elevated
      anti-annexin V IgG (P = 0.006), but not IgM (P = 0.084), was more pronounced in
      patients. Higher frequencies of elevated IgG-only (P = 0.005), but not IgM-only
      (P = 1.000; OR = 6.66), anti-annexin V antibodies were noted among patients.
      Multinomial regression analysis showed that body-mass index (overweight and
      obesity; P = 0.008), education status (P < 0.001) and anti-beta2-GPI IgM (P =
      0.033), but not IgG (P = 0.723), were associated with early abortion, while anti
      beta2-GPI IgG (P = 0.030) and anti-annexin V IgG (P = 0.004) were associated with
      late RSA. For combined early-late RSA, the only variable selected was education
      status (P < 0.001), and neither anti-annexin V nor anti-beta2-GPI IgM and IgG was
      associated with early-late RSA. Accordingly, anti-annexin V and anti-beta2-GPI
      should be regarded as independent risk markers of RSA.

PMID- 16595733
TI  - Shedding light on the distinct functions of proteoglycans.
AB  - Heparan sulfate proteoglycans (HSPGs) are ubiquitous molecules that are critical
      for signaling mediated by many growth factors, including members of the Wnt,
      transforming growth factor-beta, Hedgehog, and fibroblast growth factor families,
      and are essential for cell specification, axon guidance, and the establishment of
      morphogen gradients. Although the heparan sulfate modifications of HSPGs are
      critical, there is much to learn about how the protein cores contribute to the
      specific signaling functions of these cell-surface and matrix molecules. Recent
      work has demonstrated that glypican-1 and syndecan-1 expressed by tumor cells
      have specific roles in FGF2 signaling, affecting their responses to this
      mitogenic stimulus.

PMID- 16595734
TI  - Endogenous orphanin FQ/nociceptin is involved in the development of morphine
      tolerance.
AB  - The neuropeptide orphanin FQ/nociceptin (OFQ/N) has been shown to counteract
      several effects of endogenous and exogenous opioids, and it has been proposed as
      an opioid-modulating agent involved in the development of morphine tolerance and
      dependence. However, conflicting results have been obtained from animal models
      using different protocols to induce morphine tolerance. Here, we report that both
      genetic and pharmacological blockade of OFQ/N signaling can effectively prevent
      development of morphine tolerance. OFQ/N knockout mice injected daily with low
      doses of morphine (10 mg/kg) fail to develop tolerance even after 3 weeks of
      treatment, whereas their wild-type litter mates show profound tolerance starting
      after 10 days. Likewise, coadministration of morphine together with the synthetic
      N/OFQ peptide antagonist, J-113397 (1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl
      4-piperidyl]-3-ethyl-1,3-dihydro-2H-benzimidazol-2-one), is able to block
      tolerance development in normal mice. These data indicate that release of
      endogenous OFQ/N after morphine administration might produce a gradual decline of
      analgesic potency, i.e., tolerance. Interestingly, tolerant and nontolerant
      groups of mice receiving repeated daily low morphine doses did not differ in
      their withdrawal behavior after naloxone injection. In contrast, mice receiving
      escalating doses of morphine developed analgesic tolerance independent of their
      OFQ/N genotype, whereas withdrawal symptoms were attenuated in OFQ/N-deficient
      animals. These results indicate that the endogenous OFQ/N system is
      differentially involved in morphine tolerance development and establishment of
      opiate dependence, depending on the specific morphine dosage regimen.
      Furthermore, it suggests that OFQ/N antagonists could provide a novel therapeutic
      strategy to attenuate morphine tolerance development.

PMID- 16595735
TI  - Cilostazol protects diabetic rats from vascular inflammation via nuclear factor
      kappa B-dependent down-regulation of vascular cell adhesion molecule-1
      expression.
AB  - Vascular cell adhesion molecule (VCAM)-1 plays a critical role in the initiation
      and development of vascular inflammation and selective inhibition of adhesion
      molecules expressed by endothelial cells may present a new therapeutic strategy
      for the treatment of vascular complications associated with diabetes mellitus.
      Increasing evidence indicates that cilostazol, a cAMP phosphodiesterase
      inhibitor, reduces VCAM-1 expression on endothelial cells. In this study, we have
      tested the effect of cilostazol on the development of vascular inflammation in
      rats with streptozotocin-induced diabetes and determined the mechanism by which
      cilostazol prevents diabetes-induced vascular inflammation in the aorta. Diabetic
      rats were treated with different dose of cilostazol (27 or 9 mg/kg/day) for 8
      weeks, and aortae were removed for the evaluation of vascular inflammation. The
      VCAM-1 protein expression and VCAM-1 mRNA transcripts were analyzed by
      immunohistochemical staining and in situ hybridization assay, respectively. Our
      results demonstrated that cilostazol treatment prevents the overexpression of
      VCAM-1 and protects diabetic rats from vascular inflammation. More importantly,
      our mechanistic studies suggested that cilostazol controls the VCAM-1
      overexpression via inhibiting the activation of nuclear factor-kappaB.

PMID- 16595736
TI  - Central adenosine signaling plays a key role in centrally mediated hypotension in
      conscious aortic barodenervated rats.
AB  - We tested the hypothesis that clonidine-evoked hypotension is dependent on
      central adenosinergic pathways. Five groups of male, conscious, aortic
      baroreceptor-denervated (ABD) rats received clonidine (10 microg/kg i.v.) 30 min
      after i.v. 1) saline, 2) theophylline (10 mg/kg), or 3) 8-(p
      sulfophenyl)theophylline (8-SPT) (2.5 mg/kg) or 1 h after i.p. 4) dipyridamole (5
      mg/kg) or 5) an equal volume of sesame oil. Blockade of central (theophylline)
      but not peripheral (8-SPT) adenosine receptors abolished clonidine hypotension.
      In contrast, dipyridamole substantially enhanced the bradycardic response to
      clonidine. In additional groups, intracisternal (i.c.) dipyridamole (150 microg)
      and 8-SPT (10 microg) enhanced and abolished, respectively, clonidine (0.6 microg
      i.c.)-evoked hypotension. Because clonidine is a mixed I1/alpha2 agonist, we also
      investigated whether adenosine signaling is linked to the I1 or the alpha2A
      receptor by administering the selective I1 (rilmenidine, 25 microg) or alpha2A
      [alpha-methylnorepinephrine (alpha-MNE), 4 microg] agonist 30 min after central
      adenosine receptor blockade (8-SPT; 10 microg i.c.) or artificial cerebrospinal
      fluid. The hypotensive response elicited by rilmenidine or alpha-MNE was
      abolished in 8-SPT-pretreated rats. To delineate the role of the adenosine A2A
      receptor in clonidine-evoked hypotension, i.c. clonidine (0.6 microg) was
      administered 30 min after central adenosine receptor A2A blockade [5-amino-7-(2
      phenylethyl)-2-(2-furyl)-pyrazolo[4,3-epsilon]-1,2,4-triazolo[1,5-c]-pyrimidine
      (SCH58261); 150 microg i.c.]. The latter virtually abolished the hypotensive and
      bradycardic responses elicited by clonidine. In conclusion, central adenosine A2A
      signaling plays a key role in clonidine-evoked hypotension in conscious aortic
      barodenervated rats.

PMID- 16595737
TI  - Blockade of angiogenesis by small molecule antagonists to protease-activated
      receptor-1: association with endothelial cell growth suppression and induction of
      apoptosis.
AB  - Many studies support the notion that protease-activated receptor (PAR)-1 plays a
      pivotal role in angiogenesis. However, direct evidence and understanding the
      molecular mechanisms involved were limited because PAR-1-specific antagonists
      have been developed only recently. In the present study, we evaluated the effects
      of two well characterized PAR-1 antagonists, SCH79797 ((N-3-cyclopropyl-7-{[4-(1
      methylethyl)phenyl]-methyl}-7H-pyrrolo[3,2-f]quinazoline-1,3-diamine)) and
      RWJ56110 [(alphaS)-N-[(1S)-3-amino-1-[[(phenylmethyl)amino]carbonyl]propyl]-alpha
      [[[[[1-(2,6-dichlorophenyl)methyl]-3-(1-pyrrolidinylmethyl)-1H-indol-6
      yl]amino]carbonyl]amino]-3,4-difluorobenzenepropanamide], in the angiogenic
      cascade. These antagonists suppressed both the basic angiogenesis and that
      stimulated by thrombin in the chick chorioallantoic membrane model in vivo. PAR-1
      antagonists also abrogated tube formation in the in vitro Matrigel system. These
      inhibitory effects were dose-dependent and well correlated with the inhibitory
      effects of SCH79797 and RWJ56110 on primary endothelial cell proliferation and on
      the initiation of apoptosis. PAR-1 blockage resulted in inhibition of endothelial
      cell growth by increasing the sub-G0/G1 fraction and reducing the percentage of
      cells in the S phase. Consistent with this, PAR-1 antagonists reduced
      incorporation of [3H]thymidine in endothelial cells and blocked the
      phosphorylation of extracellular signal-regulated kinases in a fashion depending
      specifically on PAR-1 activation. Analysis by annexin V/propidium iodide staining
      and poly(ADP-ribose) polymerase cleavage revealed that PAR-1 blockage increased
      apoptotic cell death by a mechanism involving caspases. These results provide
      further evidence that PAR-1 is a key receptor that mediates angiogenesis and
      suggest PAR-1 as target for developing antiangiogenic agents with potential
      therapeutic application in cancer and other angiogenesis-related diseases.

PMID- 16595739
TI  - Effect of moderate hypothermia on gene expression by THP-1 cells: a DNA
      microarray study.
AB  - The mechanisms by which moderate hypothermia (32 degrees C for 12-72 h) affect
      human cellular function are unclear. We tested the hypothesis that it produces
      broad changes in mRNA expression in vitro. Acute monocytic leukemia (THP-1) cells
      were incubated under control conditions (37 degrees C) or moderate hypothermia
      (32 degrees C) for 24 h. RNA was extracted, and the hypothermic response was
      confirmed by examining the expression of the cold-induced RNA-binding protein
      (CIRBP) gene by RT-PCR. Gene expression analysis was performed on seven sets of
      paired samples with Affymetrix U133A chips using established statistical methods.
      Sequences were considered affected by cold if they showed statistically
      significant changes in expression and also met published post hoc filter criteria
      (changes in geometric mean expression of > or =2-fold and expression calls of
      "present" or "marginal" in at least half of the experiments). Changes in the
      expression of selected sequences were further confirmed by PCR. Sixty-seven
      sequences met the criteria for increased expression (including cold-inducible
      genes CIRBP and RNA binding motif 3), and 100 sequences showed decreased
      expression as a result of hypothermia. Functional categories affected by
      hypothermia included genes involved in immune responses; cell growth,
      proliferation, and differentiation; and metabolism and biosynthesis. Several heat
      shock proteins (HSPs) showed decreases in expression. Moderate hypothermia
      produces substantial changes in gene expression, in categories potentially of
      systemic importance. Cold exposure without rewarming decreased the expression of
      several HSPs. These in vitro findings suggest that prolonged hypothermia in vivo
      might be capable of producing physiologically relevant changes in gene expression
      by circulating leukocytes.

PMID- 16595738
TI  - Receptor regulation of gene expression of axon guidance molecules: implications
      for adaptation.
AB  - Axon guidance molecules, critical for neurodevelopment, are also implicated in
      morphological and other neurodaptative changes mediated by physiological or
      pharmacological events in adult brain. As an example, the psychostimulant cocaine
      markedly alters axon guidance molecules in adult brain of cocaine-treated rats.
      To decipher a potential link between drug-induced activation of G-protein-coupled
      receptors (GPCRs) and modulation of axon guidance molecules, we investigated
      whether GPCR activity in a SK-N-MC human neuroepithelioma cell line (which
      expresses low levels of D1 dopamine receptors) affects gene expression of axon
      guidance molecules (semaphorins, ephrins, netrins, and their receptors). Using
      real-time polymerase chain reaction, we identified 17 of 26 axon guidance
      molecules in these cells, with varying levels of expression. Forskolin, which
      raised intracellular cAMP levels 340%, increased EphA5, EphB2, and Neuropilin1
      expression, paralleling reported changes in the rat hippocampus after cocaine
      treatment. The dopamine receptor agonist dihydrexidine, which raised cAMP levels
      22%, promoted regulatory changes in EphrinA1, EphrinA5, EphB1, DCC, and
      Semaphorin3C, whereas (+/-)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H
      3-benzazepine hydrobromide (SKF81297) altered EphA5, EphrinA1, EphrinA5, and
      neuropilin1. cAMP and other signal transduction pathways may regulate gene
      expression of axon guidance molecules, potentially linking monoamine receptor
      activation to signal transduction cascades, transcriptional regulation of axon
      guidance molecules, and alterations in neural networks.

PMID- 16595740
TI  - Thermoprotection of synaptic transmission in a Drosophila heat shock factor
      mutant is accompanied by increased expression of Hsp83 and DnaJ-1.
AB  - In Drosophila larvae, acquired synaptic thermotolerance after heat shock has
      previously been shown to correlate with the induction of heat shock proteins
      (Hsps) including HSP70. We tested the hypothesis that synaptic thermotolerance
      would be significantly diminished in a temperature-sensitive strain (Drosophila
      heat shock factor mutant hsf4), which has been reported not to be able to produce
      inducible Hsps in response to heat shock. Contrary to our hypothesis,
      considerable thermoprotection was still observed at hsf4 larval synapses after
      heat shock. To investigate the cause of this thermoprotection, we conducted DNA
      microarray experiments to identify heat-induced transcript changes in these
      organisms. Transcripts of the hsp83, dnaJ-1 (hsp40), and glutathione-S
      transferase gstE1 genes were significantly upregulated in hsf4 larvae after heat
      shock. In addition, increases in the levels of Hsp83 and DnaJ-1 proteins but not
      in the inducible form of Hsp70 were detected by Western blot analysis. The mode
      of heat shock administration differentially affected the relative transcript and
      translational changes for these chaperones. These results indicate that the
      compensatory upregulation of constitutively expressed Hsps, in the absence of the
      synthesis of the major inducible Hsp, Hsp70, could still provide substantial
      thermoprotection to both synapses and the whole organism.

PMID- 16595741
TI  - Comparative SAGE analysis of the response to hypoxia in human pulmonary and
      aortic endothelial cells.
AB  - We utilized serial analysis of gene expression (SAGE) to analyze the temporal
      response of human pulmonary artery endothelial cells (HPAECs) to short-term
      chronic hypoxia at the level of transcription. Primary cultures of HPAECs were
      exposed to 1% O2 hypoxia for 8 and 24 h and compared with identical same-passage
      cells cultured under standard (5% CO2-95% air) conditions. Hierarchical
      clustering of significant hypoxia-responsive genes identified temporal changes in
      the expressions of a number of well-described gene families including those
      encoding proteins involved in thrombosis, stress response, apoptosis,
      angiogenesis, and cell proliferation. These experiments build on previously
      published data describing the transcriptomic response of human aortic endothelial
      cells (HAECs) obtained from the same donor and cultured under identical
      conditions, and we have thus taken advantage of the immortality of SAGE data to
      make direct comparisons between these two data sets. This approach revealed
      comprehensive information relating to the similarities and differences at the
      level of mRNA expression between HAECs and HPAECs. For example, we found
      differences in the cell type-specific response to hypoxia among genes encoding
      cytoskeletal factors, including paxillin, and proteins involved in metabolic
      energy production, the response to oxidative stress, and vasoreactivity (e.g.,
      endothelin-1). These efforts contribute to the expanding collection of publicly
      available SAGE data and provide a foundation on which to base further efforts to
      understand the characteristics of the vascular response to hypoxia in the
      pulmonary circulation relative to systemic vasculature.

PMID- 16595742
TI  - Cloning and functional characterization of a superfamily of microbial inwardly
      rectifying potassium channels.
AB  - Our understanding of the mammalian inwardly rectifying family of K+ channels (Kir
      family) has recently been advanced by X-ray crystal structures of two homologous
      prokaryotic orthologs (KirBac1.1 and KirBac3.1). However, the functional
      properties of these KirBac channels are still poorly understood. To address this
      problem, we cloned and characterized genes encoding KirBac orthologs from a wide
      variety of different prokaryotes and a simple unicellular eukaryote. The
      functional properties of these KirBacs were then examined by growth
      complementation in a K+ uptake-deficient strain of Escherichia coli (TK2420).
      Whereas some KirBac genes exhibited robust growth complementation, others either
      did not complement or showed temperature-dependent complementation including
      KirBac1.1 and KirBac3.1. In some cases, KirBac expression was also toxic to the
      growth of E. coli. The KirBac family exhibited a range of sensitivity to the K+
      channel blockers Ba2+ and Cs+ as well as differences in their ability to grow on
      very low-K+ media, thus demonstrating major differences in their permeation
      properties. These results reveal the existence of a functionally diverse
      superfamily of microbial KirBac genes and present an excellent resource for the
      structural and functional analysis of this class of K+ channels. Furthermore, the
      complementation assay used in this study provides a simple and robust method for
      the functional characterization of a range of prokaryotic K+ channels that are
      difficult to study by traditional methods.

PMID- 16595743
TI  - The cover. Baseball at Night.

PMID- 16595744
TI  - A piece of my mind. Duffle bag medicine.

PMID- 16595745
TI  - Mobile hospital raises questions about hospital surge capacity.

PMID- 16595746
TI  - New virus linked to prostate cancer.

PMID- 16595748
TI  - Cathepsins probed as pancreatic cancer targets.

PMID- 16595747
TI  - Emergency department overcrowding gives ambulances the runaround.

PMID- 16595749
TI  - PhD programs adopt bench-to-bedside model to speed translational research.

PMID- 16595750
TI  - Efficacy and safety of edifoligide.

PMID- 16595751
TI  - Efficacy and safety of edifoligide.

PMID- 16595752
TI  - Efficacy and safety of edifoligide.

PMID- 16595753
TI  - Strategies to prevent suicide.

PMID- 16595754
TI  - Strategies to prevent suicide.

PMID- 16595755
TI  - Risk of multiple primary melanomas.

PMID- 16595756
TI  - Interaction of duloxetine and warfarin causing severe elevation of international
      normalized ratio.

PMID- 16595758
TI  - Prevalence of overweight and obesity in the United States, 1999-2004.
AB  - CONTEXT: The prevalence of overweight in children and adolescents and obesity in
      adults in the United States has increased over several decades. OBJECTIVE: To
      provide current estimates of the prevalence and trends of overweight in children
      and adolescents and obesity in adults. DESIGN, SETTING, AND PARTICIPANTS:
      Analysis of height and weight measurements from 3958 children and adolescents
      aged 2 to 19 years and 4431 adults aged 20 years or older obtained in 2003-2004
      as part of the National Health and Nutrition Examination Survey (NHANES), a
      nationally representative sample of the US population. Data from the NHANES
      obtained in 1999-2000 and in 2001-2002 were compared with data from 2003-2004.
      MAIN OUTCOME MEASURES: Estimates of the prevalence of overweight in children and
      adolescents and obesity in adults. Overweight among children and adolescents was
      defined as at or above the 95th percentile of the sex-specific body mass index
      (BMI) for age growth charts. Obesity among adults was defined as a BMI of 30 or
      higher; extreme obesity was defined as a BMI of 40 or higher. RESULTS: In 2003
      2004, 17.1% of US children and adolescents were overweight and 32.2% of adults
      were obese. Tests for trend were significant for male and female children and
      adolescents, indicating an increase in the prevalence of overweight in female
      children and adolescents from 13.8% in 1999-2000 to 16.0% in 2003-2004 and an
      increase in the prevalence of overweight in male children and adolescents from
      14.0% to 18.2%. Among men, the prevalence of obesity increased significantly
      between 1999-2000 (27.5%) and 2003-2004 (31.1%). Among women, no significant
      increase in obesity was observed between 1999-2000 (33.4%) and 2003-2004 (33.2%).
      The prevalence of extreme obesity (body mass index > or =40) in 2003-2004 was
      2.8% in men and 6.9% in women. In 2003-2004, significant differences in obesity
      prevalence remained by race/ethnicity and by age. Approximately 30% of non
      Hispanic white adults were obese as were 45.0% of non-Hispanic black adults and
      36.8% of Mexican Americans. Among adults aged 20 to 39 years, 28.5% were obese
      while 36.8% of adults aged 40 to 59 years and 31.0% of those aged 60 years or
      older were obese in 2003-2004. CONCLUSIONS: The prevalence of overweight among
      children and adolescents and obesity among men increased significantly during the
      6-year period from 1999 to 2004; among women, no overall increases in the
      prevalence of obesity were observed. These estimates were based on a 6-year
      period and suggest that the increases in body weight are continuing in men and in
      children and adolescents while they may be leveling off in women.

PMID- 16595757
TI  - Effect of 6-month calorie restriction on biomarkers of longevity, metabolic
      adaptation, and oxidative stress in overweight individuals: a randomized
      controlled trial.
AB  - CONTEXT: Prolonged calorie restriction increases life span in rodents. Whether
      prolonged calorie restriction affects biomarkers of longevity or markers of
      oxidative stress, or reduces metabolic rate beyond that expected from reduced
      metabolic mass, has not been investigated in humans. OBJECTIVE: To examine the
      effects of 6 months of calorie restriction, with or without exercise, in
      overweight, nonobese (body mass index, 25 to <30) men and women. DESIGN, SETTING,
      AND PARTICIPANTS: Randomized controlled trial of healthy, sedentary men and women
      (N = 48) conducted between March 2002 and August 2004 at a research center in
      Baton Rouge, La. INTERVENTION: Participants were randomized to 1 of 4 groups for
      6 months: control (weight maintenance diet); calorie restriction (25% calorie
      restriction of baseline energy requirements); calorie restriction with exercise
      (12.5% calorie restriction plus 12.5% increase in energy expenditure by
      structured exercise); very low-calorie diet (890 kcal/d until 15% weight
      reduction, followed by a weight maintenance diet). MAIN OUTCOME MEASURES: Body
      composition; dehydroepiandrosterone sulfate (DHEAS), glucose, and insulin levels;
      protein carbonyls; DNA damage; 24-hour energy expenditure; and core body
      temperature. RESULTS: Mean (SEM) weight change at 6 months in the 4 groups was as
      follows: controls, -1.0% (1.1%); calorie restriction, -10.4% (0.9%); calorie
      restriction with exercise, -10.0% (0.8%); and very low-calorie diet, -13.9%
      (0.7%). At 6 months, fasting insulin levels were significantly reduced from
      baseline in the intervention groups (all P<.01), whereas DHEAS and glucose levels
      were unchanged. Core body temperature was reduced in the calorie restriction and
      calorie restriction with exercise groups (both P<.05). After adjustment for
      changes in body composition, sedentary 24-hour energy expenditure was unchanged
      in controls, but decreased in the calorie restriction (-135 kcal/d [42 kcal/d]),
      calorie restriction with exercise (-117 kcal/d [52 kcal/d]), and very low-calorie
      diet (-125 kcal/d [35 kcal/d]) groups (all P<.008). These "metabolic adaptations"
      (~ 6% more than expected based on loss of metabolic mass) were statistically
      different from controls (P<.05). Protein carbonyl concentrations were not changed
      from baseline to month 6 in any group, whereas DNA damage was also reduced from
      baseline in all intervention groups (P <.005). CONCLUSIONS: Our findings suggest
      that 2 biomarkers of longevity (fasting insulin level and body temperature) are
      decreased by prolonged calorie restriction in humans and support the theory that
      metabolic rate is reduced beyond the level expected from reduced metabolic body
      mass. Studies of longer duration are required to determine if calorie restriction
      attenuates the aging process in humans. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT00099151.

PMID- 16595760
TI  - Excessive adiposity, calorie restriction, and aging.

PMID- 16595759
TI  - Can the clinical history distinguish between organic and functional dyspepsia?
AB  - CONTEXT: Upper gastrointestinal symptoms occur in 40% of the population. An
      accurate diagnosis would help rationalize investigation and treatment. OBJECTIVE:
      To systematically review the literature of the accuracy of primary care
      physicians, gastroenterologists, or computer models in diagnosing organic
      dyspepsia. DATA SOURCES: A search of Cochrane Controlled Trials Register
      (December 2003), MEDLINE (1966-December 2003), EMBASE (1988-December 2003), and
      CINAHL (1982-December 2003) for studies that reported on cohorts of patients
      attending for endoscopy that had symptoms, clinical opinion, or both recorded
      before investigation. STUDY SELECTION: Studies that prospectively compared the
      diagnosis reached by a clinician, computer model, or both with results of upper
      gastrointestinal endoscopy in adult patients with upper gastrointestinal
      symptoms. DATA EXTRACTION: Two authors independently assessed studies (n = 79)
      for eligibility and abstracted data for estimating likelihood ratios (LRs) of
      clinical opinion, computer models, or both in diagnosing an organic cause for
      dyspepsia. DATA SYNTHESIS: Fifteen studies were identified that evaluated 11 366
      patients, with 4817 patients (42%) classified as having organic dyspepsia. The
      computer models performed similarly to the clinician; therefore, the 2 approaches
      were combined. The diagnosis reached by the clinician or computer model
      suggesting organic dyspepsia had an LR of 1.6 (95% confidence interval [CI], 1.4
      1.8), and a negative result decreased the likelihood of organic dyspepsia (LR,
      0.46; 95% CI, 0.38-0.55). A diagnosis of peptic ulcer disease performed similarly
      with an LR of 2.2 (95% CI, 1.9-2.6), but an evaluation that suggested the absence
      of peptic ulcer disease had an LR of 0.45 (95% CI, 0.38-0.53). A clinical history
      suggesting esophagitis had an LR of 2.4 (95% CI, 1.9-3.0) vs a negative history
      that had an LR of 0.50 (95% CI, 0.42-0.60). CONCLUSION: Neither clinical
      impression nor computer models that incorporated patient demographics, risk
      factors, history items, and symptoms adequately distinguished between organic and
      functional disease in patients referred for endoscopic evaluation of dyspepsia.

PMID- 16595768
TI  - JAMA patient page. Dyspepsia.

PMID- 16595769
TI  - The retinoic acid paradox in cancer chemoprevention.

PMID- 16595770
TI  - Vitamin D status and cancer incidence and mortality: something new under the sun.

PMID- 16595771
TI  - Soy and breast cancer: the controversy continues.

PMID- 16595772
TI  - Coming soon: cervical cancer vaccines, and an array of public health issues.

PMID- 16595774
TI  - Stat bite: Cervical cancer mortality worldwide.

PMID- 16595773
TI  - Who invented the VLP cervical cancer vaccines?

PMID- 16595775
TI  - In U.S., biosimilars still await FDA decision.

PMID- 16595776
TI  - EMEA tackles "generic" biologic drug issues.

PMID- 16595777
TI  - Migrant studies aid the search for factors linked to breast cancer risk.

PMID- 16595778
TI  - FDA advisory panel voices persistent safety concerns.

PMID- 16595779
TI  - Accrual delayed in adjuvant bevacizumab trial.

PMID- 16595780
TI  - Randomized phase III trial of low-dose isotretinoin for prevention of second
      primary tumors in stage I and II head and neck cancer patients.
AB  - BACKGROUND: Isotretinoin (13-cis-retinoic acid) is a synthetic vitamin A
      derivative, or retinoid, widely used in the treatment of cystic acne. Preclinical
      and clinical studies of high-dose isotretinoin in patients with head and neck
      squamous cell cancer (HNSCC) have produced encouraging results. We conducted a
      phase III randomized trial of low-dose isotretinoin versus placebo in early-stage
      HNSCC patients to assess its effect on second primary tumor incidence and
      survival. METHODS: We randomly assigned 1190 patients who had been treated for
      stage I or II HNSCC to receive either low-dose isotretinoin (30 mg/day) or
      placebo for 3 years. The patients were monitored for up to 4 more years. Survival
      was analyzed by the Kaplan-Meier method, and Cox proportional hazards models were
      used for multivariable survival analysis. All statistical tests were two-sided.
      RESULTS: Isotretinoin did not statistically significantly reduce the rate of
      second primary tumors (hazard ratio [HR] = 1.06, 95% confidence interval [CI] =
      0.83 to 1.35) or increase survival (HR = 1.03, 95% CI = 0.81 to 1.32) compared
      with placebo in patients with early-stage HNSCC. Current smokers had a higher
      rate of second primary tumors than that of never (HR = 1.64, 95% CI = 1.08 to
      2.50) or former (HR = 1.32, 95% CI = 1.01 to 1.71) smokers. The hazard ratio of
      death from any cause for current smokers versus never smokers was 2.51 (95% CI =
      1.54 to 4.10) and for current smokers versus former smokers was 1.60 (95% CI =
      1.23 to 2.07). Major sites of second primary tumors (n = 261) included lung
      (31%), oral cavity (17%), larynx (8%), and pharynx (5%). CONCLUSIONS: Low-dose
      isotretinoin was not effective in reducing the rate of second primary tumors or
      death or smoking-related disease. Smoking statistically significantly increased
      the rate of second primary tumors and death. Ongoing trials are testing higher
      doses of isotretinoin as part of combination bioadjuvant therapeutic methods for
      patients with locally advanced HNSCC.

PMID- 16595781
TI  - Prospective study of predictors of vitamin D status and cancer incidence and
      mortality in men.
AB  - BACKGROUND: Vitamin D has potent anticancer properties, especially against
      digestive-system cancers. Many human studies have used geographic residence as a
      marker of solar ultraviolet B and hence vitamin D exposure. Here, we considered
      multiple determinants of vitamin D exposure (dietary and supplementary vitamin D,
      skin pigmentation, adiposity, geographic residence, and leisure-time physical
      activity-to estimate sunlight exposure) in relation to cancer risk in the Health
      Professionals Follow-Up Study. METHODS: Among 1095 men of this cohort, we
      quantified the relation of these six determinants to plasma 25-hydroxy-vitamin D
      [25(OH)D] level by use of a multiple linear regression model. We used results
      from the model to compute a predicted 25(OH)D level for each of 47,800 men in the
      cohort based on these characteristics. We then prospectively examined this
      variable in relation to cancer risk with multivariable Cox proportional hazards
      models. RESULTS: From 1986 through January 31, 2000, we documented 4286 incident
      cancers (excluding organ-confined prostate cancer and nonmelanoma skin cancer)
      and 2025 deaths from cancer. From multivariable models, an increment of 25 nmol/L
      in predicted 25(OH)D level was associated with a 17% reduction in total cancer
      incidence (multivariable relative risk [RR] = 0.83, 95% confidence interval [CI]
      = 0.74 to 0.92), a 29% reduction in total cancer mortality (RR = 0.71, 95% CI =
      0.60 to 0.83), and a 45% reduction in digestive-system cancer mortality (RR =
      0.55, 95% CI = 0.41 to 0.74). The absolute annual rate of total cancer was 758
      per 100,000 men in the bottom decile of predicted 25(OH)D and 674 per 100,000 men
      for the top decile; these respective rates were 326 per 100,000 and 277 per
      100,000 for total cancer mortality and 128 per 100,000 and 78 per 100,000 for
      digestive-system cancer mortality. Results were similar when we controlled
      further for body mass index or physical activity level. CONCLUSIONS: Low levels
      of vitamin D may be associated with increased cancer incidence and mortality in
      men, particularly for digestive-system cancers. The vitamin D supplementation
      necessary to achieve a 25(OH)D increment of 25 nmol/L may be at least 1500
      IU/day.

PMID- 16595782
TI  - Meta-analysis of soy intake and breast cancer risk.
AB  - BACKGROUND: High intake of soy foods has been proposed to contribute to the low
      breast cancer risk in Asian countries. However, results of epidemiologic studies
      of this association are highly variable, and experimental data suggest that soy
      constituents can be estrogenic and potentially risk enhancing. Thus, rigorous
      evaluation of available epidemiologic data is necessary before appropriate
      recommendations can be made, especially for women at high risk of breast cancer
      or those who have survived the disease. METHODS: We performed a meta-analysis of
      18 epidemiologic studies (12 case-control and six cohort or nested case-control)
      published from 1978 through 2004 that examined soy exposure and breast cancer
      risk. Pooled relative risk estimates were based on either the original soy
      exposure measure defined in each study or on an estimate of daily soy protein
      intake. RESULTS: Risk estimates, levels and measures of soy exposure, and control
      for confounding factors varied considerably across studies. In a pooled analysis,
      among all women, high soy intake was modestly associated with reduced breast
      cancer risk (odds ratio [OR] = 0.86, 95% confidence interval [CI] = 0.75 to
      0.99); the association was not statistically significant among women in Asian
      countries (OR = 0.89, 95% CI = 0.71 to 1.12). Among the 10 studies that
      stratified by menopausal status the inverse association between soy exposure and
      breast cancer risk was somewhat stronger in premenopausal women (OR = 0.70, 95%
      CI = 0.58 to 0.85) than in postmenopausal women (OR = 0.77, 95% CI = 0.60 to
      0.98); however, eight studies did not provide menopause-specific results, six of
      which did not support an association. When exposure was analyzed by soy protein
      intake in grams per day, a statistically significant association with breast
      cancer risk was seen only among premenopausal women (OR = 0.94, 95% CI = 0.92 to
      0.97). CONCLUSIONS: Soy intake may be associated with a small reduction in breast
      cancer risk. However, this result should be interpreted with caution due to
      potential exposure misclassification, confounding, and lack of a dose response.
      Given these caveats and results of some experimental studies that suggest adverse
      effects from soy constituents, recommendations for high-dose isoflavone
      supplementation to prevent breast cancer or prevent its recurrence are premature.

PMID- 16595783
TI  - Gene expression profiling of primary cutaneous melanoma and clinical outcome.
AB  - BACKGROUND: Gene expression profiling data for human primary cutaneous melanomas
      are scarce because of the lack of retrospective collections of frozen tumors. To
      identify differentially expressed genes that may be involved in melanoma
      progression and prognosis, we investigated the relationship between gene
      expression profiles and clinical outcome in a cohort of patients with primary
      melanoma. METHODS: Labeled complementary RNA (cRNA) from each tissue sample was
      hybridized to a pangenomic 44K 60-mer oligonucleotide microarray. Class
      comparison and class prediction analyses were performed to identify genes whose
      expression in primary melanomas was associated with 4-year distant metastasis
      free survival among 58 patients with at least 4 years of follow-up, distant
      metastasis, or death. Results were validated immunohistochemically at the protein
      level in 176 independent primary melanomas from patients with a median clinical
      follow-up of 8.5 years. Survival was analyzed with a Cox multivariable model and
      stratified log-rank test. All statistical tests were two-sided. RESULTS: We
      identified 254 genes that were associated with distant metastasis-free survival
      of patients with primary melanoma. These 254 genes include genes involved in
      activating DNA replication origins, such as minichromosome maintenance genes and
      geminin. Twenty-three of these genes were studied at the protein level;
      expression of five (MCM4, P = .002; MCM3, P = .030; MCM6, P = .004; KPNA2, P =
      .021; and geminin, P = .004) was statistically significantly associated with
      overall survival in the validation set. In a multivariable Cox model adjusted for
      tumor thickness, ulceration, age, and sex, expression of MCM4 (hazard ratio [HR]
      of death = 4.04, 95% confidence interval [CI] = 1.39 to 11.76; P = .010) and MCM6
      (HR of death = 7.42, 95% CI = 1.99 to 27.64; P = .003) proteins was still
      statistically significantly associated with overall survival. CONCLUSION: We
      identified 254 genes whose expression was associated with metastatic
      dissemination of cutaneous melanomas. These genes may shed light on the molecular
      mechanisms underlying poor prognosis in melanoma patients.

PMID- 16595784
TI  - Prediagnostic level of serum retinol in relation to reduced risk of
      hepatocellular carcinoma.
AB  - BACKGROUND: Retinol and its derivatives (retinoids), which have antioxidant
      activity and promote cell differentiation, may protect against the development of
      hepatocellular carcinoma (HCC) by controlling hepatocellular differentiation and
      reducing inflammatory responses. METHODS: We examined prospectively the
      relationship between prediagnostic serum concentrations of retinol, alpha
      carotene; beta-carotene; beta-cryptoxanthin; lutein; lycopene; zeaxanthin; alpha
      , gamma-, and delta-tocopherols; and selenium and the risk of developing HCC
      among 213 patients with HCC and 1087 matched control subjects from a cohort of
      18,244 men in Shanghai, China, who were monitored from 1986 through 2001. Odds
      ratios (ORs) and 95% confidence intervals (CIs) for men by quartile of serum
      concentrations of micronutrients were estimated by using logistic regression with
      adjustment for cigarette smoking status, alcohol intake, self-reported history of
      physician-diagnosed hepatitis or liver cirrhosis at recruitment, and
      seropositivity for hepatitis B surface antigen (HBsAg). All statistical tests
      were two-sided. RESULTS: Men with high prediagnostic serum retinol levels had a
      lower risk of HCC than men in the lowest quartile (Q2 versus Q1, OR = 0.37, 95%
      CI = 0.22 to 0.61; Q3 versus Q1, OR = 0.30, 95% CI = 0.17 to 0.50; and Q4 versus
      Q1, OR = 0.13, 95% CI = 0.06 to 0.26; Ptrend < .001). A statistically significant
      interaction was observed between retinol and HBsAg seropositivity on HCC risk;
      HBsAg-positive men in the lowest tertile of retinol had a greater than 70-fold
      higher risk (OR = 72.7, 95% CI = 31.6 to 167.4) of HCC than HBsAg-negative men in
      the highest tertile of retinol (Pinteraction = .018). No independent effect of
      serum levels of alpha-carotene; beta-carotene; beta-cryptoxanthin; lutein;
      lycopene; zeaxanthin; alpha-, gamma-, and delta-tocopherols; or selenium on HCC
      risk were observed. CONCLUSION: High prediagnostic serum level of retinol is
      associated with a decreased risk of HCC in this population.

PMID- 16595785
TI  - Specific peptide ligand for Grb7 signal transduction protein and pancreatic
      cancer metastasis.
AB  - BACKGROUND: Pancreatic cancer is one of the most aggressive malignancies, with
      high rates of invasion and metastasis and with generally poor prognosis. We
      previously found that metastasis was strongly associated with the expression of
      growth factor receptor-bound protein 7 (Grb7), which contains a Src homology 2
      (SH2) domain. In this study, we evaluated Grb7 protein as a molecular target of
      therapy for metastatic pancreatic cancer. METHODS: Grb7 protein expression was
      measured by immunohistochemistry in 36 human pancreatic cancer specimens and
      adjacent normal pancreatic tissue. We synthesized a nonphosphorylated peptide
      inhibitor that binds specifically to the SH2 domain of Grb7. Intracellular
      signaling was assessed by immunoprecipitation and immunoblot assays in cultured
      human pancreatic cancer cells. Cell migration was measured with a modified Boyden
      chamber method. Peritoneal metastasis of the pancreatic cancer cells was measured
      with a mouse model. All statistical tests were two-sided. RESULTS: We found that
      22 (61%) of 36 pancreatic cancer specimens had higher levels of Grb7 protein than
      their corresponding normal pancreatic tissue specimens. Grb7 expression was
      statistically significantly different between specimens from patients without
      lymph node metastasis (stage N0; two of the 10 patients) and patients with lymph
      node metastasis (stages N1 + N2; 20 of the 26 patients) (P = .006). The Grb7
      peptide inhibitor selectively blocked the interaction between Grb7 and focal
      adhesion kinase and blocked the phosphorylation of Grb7 protein. In vivo Grb7
      peptide inhibitor statistically significantly attenuated cell migration (for
      control peptide, 87.5 cells migrated, 95% confidence interval [CI] = 82.6 to 92.4
      cells; for Grb7 peptide, 5.7 cells migrated, 95% CI = 2.3 to 9.0 cells; P < .001)
      and peritoneal metastasis of the pancreatic cancer cells in a mouse model, as
      assessed by the number of nodules (control = 72.6 nodules, 95% CI = 55.8 to 89.4
      nodules; and for Grb7 peptide = 3.2 nodules, 95% CI = 1.6 to 4.8 nodules; P <
      .001, t test) and their weight (control = 4.13 g, 95% CI = 3.40 to 4.86 g; Grb7
      peptide = 0.19 g, 95% CI = 0.06 to 0.32 g; P < .001, t test). CONCLUSIONS: The
      Grb7 peptide inhibitor appears to be a promising molecularly targeted therapeutic
      agent against metastatic pancreatic cancer.

PMID- 16595786
TI  - Effect of nurse-directed hypertension treatment among First Nations people with
      existing hypertension and diabetes mellitus: the Diabetes Risk Evaluation and
      Microalbuminuria (DREAM 3) randomized controlled trial.
AB  - BACKGROUND: First Nations people with diabetes mellitus and hypertension are at
      greater risk of renal and cardiovascular complications than are non-native
      patients because of barriers to health care services. We conducted this
      randomized controlled trial to assess whether a community-based treatment
      strategy implemented by home care nurses would be effective in controlling
      hypertension in First Nations people with existing hypertension and type 2
      diabetes. METHODS: We compared 2 community-based strategies for controlling
      hypertension in First Nations people with existing hypertension and diabetes. In
      the intervention group, a home care nurse followed a predefined treatment
      algorithm of pharmacologic antihypertensive therapy. In the control group,
      treatment decisions were made by each subject's primary care physician. The
      primary outcome measure was the difference between the 2 groups in the change in
      systolic blood pressure after 12 months. Secondary outcome measures were the
      change in diastolic blood pressure over time, the change in urine albumin status
      and the incidence of adverse events. RESULTS: Both groups experienced a
      significant reduction in systolic blood pressure by the final visit (by 24.0
      [standard deviation (SD) 13.5] mm Hg in the intervention group and by 17.0 [SD
      18.6] mm Hg in the control group); p < 0.001 in each case). However, the
      difference between the 2 groups in this change was not significant. Patients in
      the intervention group had a larger decrease in diastolic blood pressure over
      time than did those in the control group (by 11.6 [SD 10.6] mm Hg v. 6.8 [SD
      11.1] mm Hg respectively; p = 0.05). The groups did not differ significantly in
      terms of changes in urine albumin excretion or incidence of adverse events.
      INTERPRETATION: High rates of blood pressure control in the community were
      achieved in both groups in the DREAM 3 study. The addition of a home care nurse
      to implement a treatment strategy for blood pressure control was more effective
      in lowering diastolic than systolic blood pressure compared with home care visits
      for blood pressure monitoring alone and follow-up treatment by a family
      physician.

PMID- 16595787
TI  - Analysis of human antibodies to erythrocyte binding antigen 175 peptide 4 of
      Plasmodium falciparum.
AB  - BACKGROUND: The IgG1 and IgG3 antibodies are considered cytophilic and protective
      against Plasmodium falciparum, whereas IgG2 and IgG4 are thought to block
      protective mechanisms. OBJECTIVES: The main objective was to measure antibodies
      directed against erythrocyte binding antigen-175 (EBA-175) peptide 4 and analyze
      the relationship between such antibodies and clinical malaria attack. METHODS:
      Using an enzyme-linked immunosorbent assay, a retrospective analysis of naturally
      acquired antibodies to synthetic peptide from EBA-175 peptide 4 has been carried
      out in 158 school children from the village of Dienga in Gabon. RESULTS: The
      overall prevalence rates of antibodies to EBA-175 peptide 4 were 85.2%, 66.8%,
      52.6%, 71.6% and 64.0% for total IgG, IgG1, IgG2, IgG3 and IgG4, respectively.
      Protection from clinical malaria, determined after a prospective 1-year study,
      was associated with the levels of IgG and IgG1 antibodies that increased with
      age. CONCLUSION: Together, these data suggest that age/exposure-related
      acquisition of anti-EBA-175 antibodies may contribute to the development of
      clinically protective immunity and could be taken into account in malaria control
      strategies when they are confirmed.

PMID- 16595788
TI  - Imbalanced distribution of Plasmodium falciparum EBA-175 genotypes related to
      clinical status in children from Bakoumba, Gabon.
AB  - OBJECTIVE: The erythrocyte binding antigen 175 kDa (EBA-175) of Plasmodium
      falciparum is one of the major ligands for red blood cell invasion by merozoites.
      EBA-175 is a dimorphic antigen but the role that dimorphism plays in host
      parasite interaction is not fully understood. In this study, we sought to
      determine the distribution of EBA-175 genotypes and its pathogenetic influence.
      METHODS: The nested polymerase chain reaction was used to determine the genotypes
      of P. falciparum isolates from asymptomatic and symptomatic Gabonese children.
      RESULTS: CAMP strains (C-segment) and FCR-3 strains (F-segment) were found in
      13/50 (26%) and 19/50 (38%) symptomatic children, respectively and in 16/66 (24%)
      and 46/66 (70%) asymptomatic children, respectively. The prevalence of mixed C-/F
      infection was 18/50 (36%) and 4/66 (6%) in symptomatic and asymptomatic
      children, respectively. CONCLUSIONS: These results show that mixed C-/F-
      infection is associated with clinical malaria (chi2, P <0.01) and may have
      important therapeutic implications.

PMID- 16595789
TI  - The Siblings With Ischemic Stroke Study (SWISS): a progress report.
AB  - There is increasing evidence that genetic factors are associated with ischemic
      stroke, including multiple recent reports of association with the gene PDE4D,
      encoding phosphodiesterase 4D, on chromosome 5q12. Genetic studies of stroke are
      important but can be logistically difficult to perform. This article reviews the
      design of the Siblings With Ischemic Stroke Study (SWISS) and discusses problems
      in performing a sibling-based pedigree study where proband-initiated consent is
      used to enroll pedigree members. Proband-initiated enrollment optimizes privacy
      protections for family members, but it is associated with a substantial pedigree
      non-completion rate such that 3 to 4 probands must be identified to obtain one
      completed sibling pedigree. This report updates the progress of enrollment in the
      SWISS protocol, discusses barriers to pedigree completion and describes
      innovative approaches used by the SWISS investigators to enhance enrollment.

PMID- 16595790
TI  - The role of echocardiography in diagnosing space-occupying lesions of the heart.
AB  - In contrast to primary cardiac tumors, which are less frequent and mostly benign
      in nature, the majority of intracardiac tumors are metastatic lesions. Cardiac
      ultrasound has evolved enormously since its emergence in the 1950s and is
      presently the modality of choice for imaging space-occupying lesions of the
      heart; it provides high quality, real-time images that are extremely valuable in
      the evaluation of cardiac masses. Although transthoracic echocardiography is an
      excellent initial diagnostic technique to evaluate and diagnose cardiac masses,
      transesophageal echocardiography provides superior image resolution and better
      visualization of cardiac masses in patients with suboptimal transthoracic
      echocardiography studies. Computed tomography and magnetic resonance imaging are
      additional tools used for cardiac imaging and may provide useful information in
      addition to that obtained by echocardiography, especially when the images
      obtained by the latter are suboptimal.

PMID- 16595791
TI  - Interactions between natural killer cells, cortisol and prolactin in malaria
      during pregnancy.
AB  - Natural killer cells derived from pluripotent hematopoietic stem cells are
      important cells of the immune system that have two main functions: a cytolytic
      activity and a cytokine-producing capacity. These functions are tightly regulated
      by numerous activating and inhibitory receptors, including newly discovered
      receptors that selectively trigger the cytolytic activity in a major
      histocompatibility complex independent manner. Based on their defining function
      of spontaneous cytotoxicity without prior immunization, natural killer (NK) cells
      have been thought to play a critical role in immune surveillance and cancer
      therapy. New insights into NK cell biology have suggested their major roles in
      the control of infections, particularly in Plasmodium falciparum infection and in
      fetal implantation. P. falciparum is the main protozoan parasite responsible for
      malaria causing 200-300 million clinical cases and killing over 3 million people
      each year. This review provides an update on NK cell function, ontogeny and
      biology in order to better understand the role of NK cells in pregnancy in
      regions where malaria is endemic. Understanding mechanisms of NK cell functions
      may lead to novel therapeutic strategies for the treatment of human disease, in
      general, and particularly in the fight against malaria.

PMID- 16595792
TI  - Dysregulation of cell adhesion proteins and cardiac arrhythmogenesis.
AB  - Proper mechanical and electrical coupling of cardiomyocytes is crucial for normal
      propagation of the electrical impulse throughout the working myocardium. Various
      proteins on the surface of cardiomyocytes are responsible for the integration of
      structural information and cell-cell communication. Increasing evidence from
      diseased myocardium and animal models indicates that alteration in electrical
      coupling via gap junctions is a critical determinant in the development of an
      arrhythmogenic substrate. What is less clear is how gap junctions are maintained
      and regulated in the working myocardium. In this review, we present data from
      human disease and animal models that support the idea that cell adhesion proteins
      regulate the stability of the gap junction protein, connexin.

PMID- 16595795
TI  - Cardiac enzymes, renal failure and renal transplantation.
AB  - Diagnostic accuracy of the currently available serum markers of cardiac injury,
      such as myoglobin, creatine kinase and its myocardial isoform, are altered in
      patients with renal failure. It is shown that cardiac troponins have decreased
      diagnostic sensitivity and specificity in patients receiving renal replacement
      therapy. Data regarding serum levels of these cardiac biomarkers, especially
      those of the cardiac troponins, in patients with a transplanted kidney are
      limited. Current data show that levels of cardiac troponin I are unaltered in
      patients who have undergone renal transplantation, while levels of cardiac
      troponin T may be elevated.We believe that cardiac troponin I should be the
      biomarker of choice for diagnosis of myocardial injury in these patients.
      However, further trials are required for conclusive results.

PMID- 16595794
TI  - Hereditary hemorrhagic telangiectasia, a vascular dysplasia affecting the TGF
      beta signaling pathway.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is caused by mutations in endoglin
      (ENG; HHT1) or ACVRL1/ALK1 (HHT2) genes and is an autosomal dominant vascular
      dysplasia. Clinically, HHT is characterized by epistaxis, telangiectases and
      arteriovenous malformations in some internal organs such as the lung, brain or
      liver. Endoglin and ALK1 proteins are specific endothelial receptors of the
      transforming growth factor (TGF)-beta superfamily that are essential for vascular
      integrity. Genetic studies in mice and humans have revealed the pivotal role of
      TGF-beta signaling during angiogenesis. Through binding to the TGF-beta type II
      receptor, TGF-beta can activate two distinct type I receptors (ALK1 and ALK5) in
      endothelial cells, each one leading to opposite effects on endothelial cell
      proliferation and migration. The recent isolation and characterization of
      circulating endothelial cells from HHT patients has revealed a decreased endoglin
      expression, impaired ALK1- and ALK5-dependent TGF-beta signaling, disorganized
      cytoskeleton and the failure to form cord-like structures which may lead to the
      fragility of small vessels with bleeding characteristic of HHT vascular dysplasia
      or to disrupted and abnormal angiogenesis after injuries and may explain the
      clinical symptoms associated with this disease.

PMID- 16595797
TI  - Attenuation of DNA charge transport by compaction into a nucleosome core
      particle.
AB  - The nucleosome core particle (NCP) is the fundamental building block of chromatin
      which compacts approximately 146 bp of DNA around a core histone protein octamer.
      The effects of NCP packaging on long-range DNA charge transport reactions have
      not been adequately assessed to date. Here we study DNA hole transport reactions
      in a 157 bp DNA duplex (AQ-157TG) incorporating multiple repeats of the DNA TG
      motif, a strong NCP positioning sequence and a covalently attached Anthraquinone
      photooxidant. Following a thorough biophysical characterization of the structure
      of AQ-157TG NCPs by Exonuclease III and hydroxyl radical footprinting, we
      compared the dynamics of DNA charge transport in ultraviolet-irradiated free and
      NCP-incorporated AQ-157TG. Compaction into a NCP changes the charge transport
      dynamics in AQ-157TG drastically. Not only is the overall yield of oxidative
      lesions decreased in the NCPs, but the preferred sites of oxidative damage change
      as well. This NCP-dependent attenuation of DNA charge transport is attributed to
      DNA-protein interactions involving the folded histone core since removal of the
      histone tails did not perturb the charge transport dynamics in AQ-157TG NCPs.

PMID- 16595796
TI  - Molecular beacons with intrinsically fluorescent nucleotides.
AB  - We report the design, synthesis and characterization of a novel molecular beacon
      (MB-FB) which uses the fluorescent bases (FB) 2-aminopurine (AP) and pyrrolo-dC
      (P-dC) as fluorophores. Because the quantum yield of these FB depend on
      hybridization with complementary target, the fluorescent properties of MB-FB were
      tuned by placing the FB site specifically within the MB such that hybridization
      with complementary sequence switches from single strand to double strand for AP
      and vice versa for P-dC. The MB-FB produces a ratiometric fluorescence increase
      (the fluorescence emission of P-dC over that of AP in the presence and absence of
      complementary sequence) of 8.5 when excited at 310 nm, the maximum absorption of
      AP. This ratiometric fluorescence is increased to 14 by further optimizing
      excitation (325 nm). The fluorescence lifetime is also affected by the addition
      of target, producing a change in the long-lived component from 6.5 to 8.7 ns
      (Exc. 310 nm, Em. 450 nm). Thermal denaturation profiles monitored at 450 nm (P
      dC emission) show a cooperative denaturation of the MB-FB with a melting
      temperature of 53 degrees C. The thermal denaturation profile of MB-FB hybridized
      with its target shows a marked fluorescence reduction at 53 degrees C, consistent
      with a transition from double stranded helix to random coil DNA.

PMID- 16595798
TI  - NMR structure of the Aquifex aeolicus tmRNA pseudoknot PK1: new insights into the
      recoding event of the ribosomal trans-translation.
AB  - The transfer-messenger RNA (tmRNA) pseudoknot PK1 is essential for bacterial
      trans-translation, a ribosomal rescue mechanism. We report the solution structure
      of PK1 from Aquifex aeolicus, which despite an unprecedented small number of
      nucleotides and thus an unprecented compact size, displays a very high thermal
      stability. Several unusual structural features account for these properties and
      indicate that PK1 belongs to the class of ribosomal frameshift pseudoknots. This
      suggests a similarity between the mechanism of programmed ribosomal frameshifting
      and trans-translation.

PMID- 16595793
TI  - Recent advances in understanding endothelial dysfunction in atherosclerosis.
AB  - Over the last two decades, it has become evident that decreased bioavailability
      of endothelial nitric oxide (NO) produced from endothelial NO synthase (eNOS),
      referred to as endothelial dysfunction, plays a crucial role in the development
      and progression of atherosclerosis. Much progress has been made in understanding
      the mechanisms of decreased endothelial NO bioavailability at the levels of
      regulation of eNOS gene expression, eNOS enzymatic activity and NO inactivation.
      Initial studies suggest that increasing eNOS gene expression would improve
      endothelial NO release in the hope of inhibiting the progression of
      atherosclerosis. Recent experimental studies, however, do not always support this
      therapeutic concept and show some evidence that overexpression of eNOS in
      atherosclerosis may be even harmful for the disease progression.Thus, recent
      research to improve endothelial function in atherosclerosis has focused on
      regulation of eNOS enzymatic activity and prevention of NO inactivation by
      oxidative stress. Since the role of oxidative stress in endothelial NO
      bioavailability has been reviewed in a large number of comprehensive articles,
      this article focuses on the relevant regulatory mechanisms of eNOS enzymatic
      activity that are emerging to play a role in endothelial dysfunction in
      atherosclerosis.

PMID- 16595799
TI  - Isolation of human Dna2 endonuclease and characterization of its enzymatic
      properties.
AB  - In eukaryotes, the creation of ligatable nicks in DNA from flap structures
      generated by DNA polymerase delta-catalyzed displacement DNA synthesis during
      Okazaki fragment processing depends on the combined action of Fen1 and Dna2.
      These two enzymes contain partially overlapping but distinct endonuclease
      activities. Dna2 is well-suited to process long flaps, which are converted to
      nicks by the subsequent action of Fen1. In this report, we purified human Dna2 as
      a recombinant protein from human cells transfected with the cDNA of the human
      homologue of Saccharomyces cerevisiae Dna2. We demonstrated that the purified
      human Dna2 enzyme contains intrinsic endonuclease and DNA-dependent ATPase
      activities, but is devoid of detectable DNA helicase activity. We determined a
      number of enzymatic properties of human Dna2 including its substrate specificity.
      When both 5' and 3' tailed ssDNAs were present in a substrate, such as a forked
      structured one, both single-stranded regions were cleaved by human Dna2 (hDna2)
      with equal efficiency. Based on this and other properties of hDna2, it is likely
      that this enzyme facilitates the removal of 5' and 3' regions in equilibrating
      flaps that are likely to arise during the processing of Okazaki fragments in
      human cells.

PMID- 16595803
TI  - Proposal ties financial incentives to development of drugs for neglected
      diseases.

PMID- 16595802
TI  - Colistin makes a limited comeback.

PMID- 16595800
TI  - Biochemical analysis of human Dna2.
AB  - Yeast Dna2 helicase/nuclease is essential for DNA replication and assists FEN1
      nuclease in processing a subset of Okazaki fragments that have long single
      stranded 5' flaps. It is also involved in the maintenance of telomeres. DNA2 is a
      gene conserved in eukaryotes, and a putative human ortholog of yeast DNA2
      (ScDNA2) has been identified. Little is known about the role of human DNA2
      (hDNA2), although complementation experiments have shown that it can function in
      yeast to replace ScDNA2. We have now characterized the biochemical properties of
      hDna2. Recombinant hDna2 has single-stranded DNA-dependent ATPase and DNA
      helicase activity. It also has 5'-3' nuclease activity with preference for single
      stranded 5' flaps adjacent to a duplex DNA region. The nuclease activity is
      stimulated by RPA and suppressed by steric hindrance at the 5' end. Moreover,
      hDna2 shows strong 3'-5' nuclease activity. This activity cleaves single-stranded
      DNA in a fork structure and, like the 5'-3' activity, is suppressed by steric
      hindrance at the 3'-end, suggesting that the 3'-5' nuclease requires a 3' single
      stranded end for activation. These biochemical specificities are very similar to
      those of the ScDna2 protein, but suggest that the 3'-5' nuclease activity may be
      more important than previously thought.

PMID- 16595804
TI  - Health event aids San Antonio's Hispanic residents.

PMID- 16595805
TI  - Long-term maintenance of sterility in single-use syringes.

PMID- 16595806
TI  - Phosphate binders.

PMID- 16595808
TI  - Defining the phases of clinical trials.

PMID- 16595809
TI  - Drug information specialists.

PMID- 16595810
TI  - Lobbying: A professionwide responsibility.

PMID- 16595811
TI  - Life on Capitol Hill: A pharmacist's perspective.

PMID- 16595812
TI  - Safety of high-dose iron sucrose infusion in hospitalized patients with chronic
      kidney disease.
AB  - PURPOSE: The safety of high-dose iron sucrose infusion in hospitalized patients
      with chronic kidney disease was studied. METHODS: A retrospective analysis was
      conducted at a 478-bed community hospital. A medical informatics search was
      performed to identify all hospitalized patients who were prescribed i.v. iron
      sucrose to deliver elemental iron 300 mg every other day for three doses between
      January and December 2002. Patients were eligible for inclusion in the analysis
      if they had chronic kidney disease, had an estimated creatinine clearance of <60
      mL/min, and were prescribed the above regimen. Information on iron
      administration, vital signs, hematologic values, and iron indexes was gathered
      from patients' medical records. Medical record review was also used to identify
      possible adverse events. RESULTS: A total of 73 patients met eligibility criteria
      and received a total of 167 doses of iron sucrose. Twenty adverse events were
      judged as possibly related to iron sucrose administration and included nausea (n
      = 8 events), reduced blood pressure (n = 4), vomiting (n = 2), dysgeusia (n = 2),
      constipation (n = 2), fatigue (n = 1), and anxiety (n = 1). The majority of these
      adverse events were low in severity, as determined by an objective scale. No
      severe adverse events occurred. There was no association between infusion rate
      and the occurrence of potential adverse events (p = 0.44). CONCLUSION: Every
      other-day i.v. infusion of iron sucrose, to deliver elemental iron 300 mg/dose,
      was associated with adverse events that were relatively uncommon, minor in
      severity, and unlikely to require medical intervention.

PMID- 16595813
TI  - An integrated pharmacoeconomic approach to antimicrobial formulary decision
      making.
AB  - PURPOSE: The utility of a novel interdisciplinary approach to antimicrobial
      formulary decision-making was studied. METHODS: Pseudomonas aeruginosa minimum
      inhibitory concentration (MIC) distribution data for cefepime and ceftazidime
      were retrieved from nonrepeat isolates obtained from November 2002 to October
      2003. Unbound drug exposures were simulated for 5000 patients using the Monte
      Carlo method. Weighted target attainment rates (TARs) were calculated for
      cefepime and ceftazidime 1 g every 8 hours and 1 g every 12 hours (infused over
      0.5, 2, and 4 hours), using three representative pharmacodynamic targets
      (percentage of time above the MIC of 67%, 100%, and 400%). RESULTS: MIC data for
      1230 nonrepeat P. aeruginosa were analyzed. The MIC at which 90% of the P.
      aeruginosa isolates were inhibited was 16 and 32 mg/L for cefepime and
      ceftazidime, respectively. Drug acquisition cost was the highest with cefepime 1
      g given every 8 hours (37.56 dollars/day), followed by cefepime 1 g every 12
      hours (25.04 dollars/day) and ceftazidime 1 g every 8 hours (22.26 dollars/day).
      When infused over 0.5 hour, the highest TAR was achieved with cefepime 1 g every
      8 hours (82%), followed by ceftazidime 1 g every 8 hours (77%) and cefepime 1 g
      every 12 hours (66%); ceftazidime 1 g every 8 hours was 70% more cost-effective
      than cefepime 1 g every 8 hours. Cefepime 1 g every 12 hours, infused over 4
      hours, increased the TAR to 89% and was similar in cost-effectiveness to
      ceftazidime 1 g every 8 hours infused over 0.5 hour. CONCLUSION: An integrated
      pharmacoeconomic approach to antimicrobial formulary decision-making addressed
      local resistance patterns, population pharmacokinetics, pharmacodynamics, dosing
      regimens, and drug acquisition costs. This method appeared to be more realistic
      and objective than the conventional approach of considering only drug acquisition
      costs, especially for agents in a similar structural or functional class.

PMID- 16595814
TI  - Medication discrepancies affecting senior patients at hospital admission.

PMID- 16595816
TI  - Accuracy and reproducibility of small-volume injections from various-sized
      syringes.

PMID- 16595815
TI  - Agreement between medical record documentation and patient-reported use of
      nonsteroidal antiinflammatory drugs.

PMID- 16595818
TI  - Implementing a standardized safety procedure for continuous renal replacement
      therapy solutions.

PMID- 16595817
TI  - Pharmacoeconomics of continuous versus intermittent infusion of piperacillin
      tazobactam for the treatment of complicated intraabdominal infection.

PMID- 16595819
TI  - Dietary calcium, calcium supplements, and the risk of calcium oxalate kidney
      stones.

PMID- 16595820
TI  - Why commutability matters.

PMID- 16595821
TI  - How should we measure the albumin in urine?

PMID- 16595822
TI  - Is the DNA sequence the gold standard in genetic testing? Quality of molecular
      genetic tests assessed.

PMID- 16595823
TI  - Tracking microchimeric DNA in plasma to diagnose and manage organ transplant
      rejection.

PMID- 16595824
TI  - Estimation and application of biological variation of urinary delta
      aminolevulinic acid and porphobilinogen in healthy individuals and in patients
      with acute intermittent porphyria.
AB  - BACKGROUND: Diagnosis of an attack of acute intermittent porphyria (AIP) is based
      on the demonstration of increased concentrations of porphobilinogen (PBG) and
      delta-aminolevulinic acid (ALA) in urine, but many AIP patients also have high
      baseline concentrations in remission. The aim of this study was to estimate the
      biological variations of ALA, PBG, and porphyrins in healthy individuals and AIP
      patients to improve interpretation of test results. METHODS: Fifteen healthy
      individuals and 15 AIP patients were included, and biological variations were
      calculated based on urine samples collected weekly for 10 consecutive weeks. For
      the AIP patients, long-term variations were also estimated based on 7 samples
      collected through a 2-year period. RESULTS: The porphyrin variances were
      inhomogeneously distributed; biological variations of porphyrins were therefore
      not calculated. The within-subject biological variations of ALA and PBG were 16%
      20% in the short-term settings and for PBG, 25% in the long-term setting, giving
      reference change values of approximately 50% and 70%, respectively. The
      probability of detecting a 100% real change in PBG was 97% in the short-term
      setting and 80% in the long-term setting. CONCLUSIONS: In an AIP patient, a 2
      fold increase in PBG, independent of the baseline concentration, will be detected
      with a probability >80% and is most likely related to the patient's disease and
      not caused only by analytical and biological variation. When PBG is used in the
      assessment of AIP-related symptoms, both the PBG concentration in remission and
      the length of time since the previous sample must be considered.

PMID- 16595825
TI  - Clinical utility of an automated immunochemiluminometric thyroglobulin assay in
      differentiated thyroid carcinoma.
AB  - BACKGROUND: Thyroglobulin (Tg) measurements are important in the follow-up of
      patients with differentiated thyroid carcinoma (DTC). We evaluated the analytical
      and clinical performance of a new automated immunochemiluminometric assay for Tg
      (Tg-ICMA; Nichols Advantage Tg; Nichols Institute Diagnostics). METHODS: We used
      the Tg-ICMA to measure Tg concentrations in serum samples from 110 Tg antibody
      negative DTC patients undergoing thyroid-hormone suppression therapy. Disease
      state at the time of measurement was assessed on the basis of routine follow-up
      data. We compared the clinical performance of this assay with the routinely used
      IRMA (ELSA-hTG; CIS Bio International). RESULTS: The detection limit and
      functional sensitivity of the Tg-ICMA, based on direct calibration to CRM-457,
      were 0.05 and 0.6 microg/L, respectively. No Tg-IRMA-positive cases were missed
      by the Tg-ICMA. Tg was measurable by Tg-ICMA (0.6-8.6 microg/L) but undetectable
      by Tg-IRMA (<1.5 microg/L) in 12 patients (11%). Clinical data showed evidence of
      disease in 4 of 12 patients (33%). CONCLUSIONS: The Tg-ICMA is a sensitive and
      reproducible assay for identifying patients in follow-up for DTC with evidence of
      disease, but uncertainty remains with regard to interpreting findings of
      measurable serum Tg in patients with no evidence of disease. Follow-up data are
      required to determine the predictive value of these isolated Tg results. New
      concepts, i.e., serial Tg measurements and risk stratification of patients, need
      to be tested to confirm the applicability of this assay for clinical practice.

PMID- 16595827
TI  - Organic solvents compromise performance of internal standard (ascomycin) in
      proficiency testing of mass spectrometry-based assays for tacrolimus.

PMID- 16595826
TI  - Analysis of methylmalonic acid in plasma by liquid chromatography-tandem mass
      spectrometry.
AB  - BACKGROUND: Methylmalonic acid (MMA) is a biochemical marker for cobalamin
      deficiency, particularly in cases where the cobalamin concentration is moderately
      decreased or in the low-normal range. Liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) with electrospray ionization is a rapid, robust method
      that has been used in MMA analysis. We developed a simple method combining solid
      phase extraction (SPE) and derivatization to prepare serum or plasma for LC-MS/MS
      analysis of MMA. METHODS: Deuterated internal standard d(3)-MMA was added to
      serum or plasma before SPE on strong anion-exchange (SAX) columns. After elution
      with HCl-butanol (10:90 by volume) and addition of 1 g/L formic acid, the samples
      were simultaneously derivatized and evaporated by heating to 70 degrees C for 15
      min followed by 54 degrees C overnight in uncapped vials. Acetonitrile and 1 g/L
      formic acid were added to the samples before injection into the LC-MS/MS system.
      MMA and d(3)-MMA were quantified in the multiple-reaction monitoring mode.
      Calibrators were prepared in serum by the standard addition method. RESULTS: The
      MMA assay was linear up to 200 micromol/L. Interassay CVs were 6.7%, 5.0%, and
      5.0% for mean concentrations of 0.15, 0.36, and 0.65 micromol/L, respectively.
      CONCLUSIONS: Our simplified sample preparation and derivatization method is
      suitable for use in MMA analyses. MMA elutes with the derivatization reagent, and
      derivatization and evaporation are performed simply by leaving the uncapped vials
      in a heating block overnight. The method shows good linearity and precision.

PMID- 16595828
TI  - Influence of sampling and storage conditions on B-type natriuretic peptide
      immunoreactivity for 3 automated assays.

PMID- 16595829
TI  - Use of B-type natriuretic peptide testing in a community teaching hospital 4
      years after implementation and agreement of results with discharge diagnoses.

PMID- 16595831
TI  - Six Sigma and calculated laboratory tests.

PMID- 16595830
TI  - Pediatric tube direct sampling by the Abbott Architect integrated ci8200
      chemistry/immunochemistry analyzer.

PMID- 16595832
TI  - Validation of breast cancer biomarkers identified by mass spectrometry.

PMID- 16595833
TI  - Pretreatment of serum with penicillamine: effects on capillary electrophoresis
      patterns and on immunonephelometric measurement of immunoglobulins.

PMID- 16595835
TI  - Use of serum on Guthrie cards in screening for congenital disorders of
      glycosylation.

PMID- 16595836
TI  - Prenatal diagnosis of guanidinoacetate methyltransferase deficiency: increased
      guanidinoacetate concentrations in amniotic fluid.

PMID- 16595837
TI  - Smoking acutely increases plasma ghrelin concentrations.

PMID- 16595838
TI  - Effect of Plasmodium falciparum parasitemia on erythrocyte zinc protoporphyrin.

PMID- 16595839
TI  - Multiplex PCR assay for the identification and differentiation of all Brucella
      species and the vaccine strains Brucella abortus S19 and RB51 and Brucella
      melitensis Rev1.

PMID- 16595840
TI  - Influence of PON1 polymorphisms on the association between serum paraoxonase 1
      and homocysteinemia in a general population.

PMID- 16595841
TI  - Tumor M2 pyruvate kinase as a stool marker for colorectal cancer: stability at
      room temperature and implications for application in the screening setting.

PMID- 16595842
TI  - Potentially inappropriate repeat laboratory testing in inpatients.

PMID- 16595843
TI  - Glycerol and ethanol in red wine are responsible for urate-related increases in
      plasma antioxidant capacity.

PMID- 16595844
TI  - Effect of delayed processing on high-sensitivity C-reactive protein.

PMID- 16595845
TI  - Child maltreatment trends in the 1990s: why does neglect differ from sexual and
      physical abuse?
AB  - Substantiated cases of child maltreatment have declined more than 20% since a
      peak in 1993. However, although sexual abuse and physical abuse showed
      significant declines during the 1990s (47% and 36%, respectively), neglect
      fluctuated, with only a small overall decline during this period (7%). Available
      data suggest that at least part of the declines in sexual and physical abuse is
      likely to be real. Some evidence also suggests that a decline in neglect may have
      been masked in some states. Possible sources for declines in child maltreatment
      include direct prevention efforts, economic improvements, more aggressive
      criminal justice efforts, dissemination of psychiatric medication, and
      generational changes. Public health models suggest that population-level
      prevention initiatives are the most promising options for further reducing
      maltreatment rates. However, better epidemiological and evaluation research will
      be needed to identify the key factors.

PMID- 16595846
TI  - Attributional style as a mediator between parental abuse risk and child
      internalizing symptomatology.
AB  - This study examined a model wherein children's attributional style mediates the
      relationship between parental physical child-abuse risk and children's
      internalizing problems. Using structural equation modeling, three indices of
      abuse risk were selected (child abuse potential, physical discipline use, and
      dysfunctional parenting style) and two indices of children's internalizing
      problems (depression and anxiety). The sample included 75 parent-child dyads, in
      which parents reported on their abuse risk and children independently completed
      measures of depressive and anxious symptomatology and a measure on their
      attributional style. Findings supported the model that children's attributional
      style for positive events (but not negative events) partially mediated the
      relationship between abuse risk and internalizing symptoms, with significant
      direct and indirect effects of abuse risk on internalizing symptomatology. Future
      directions to continue evaluating additional mediators and other possible
      contextual variables are discussed.

PMID- 16595847
TI  - Sexual revictimization: the role of sexual self-esteem and dysfunctional sexual
      behaviors.
AB  - Disproportionately high rates of sexual revictimization have been noted among
      former victims of child sexual abuse (CSA), yet researchers have yet to determine
      the source of this apparent vulnerability to reexperience sexual violence. This
      study explores this issue by examining sexual self-esteem, sexual concerns, and
      sexual behaviors among 402 university women. Compared to women without a history
      of CSA (n = 348), women with a history of CSA (n = 54) had lower sexual self
      esteem, poorer sexual adjustment, and were 2 times more likely to have
      experienced sexual assault since the age of 14 years. Structural equation
      modeling indicated that the relationship between child abuse (i.e., CSA and child
      psychological maltreatment) and sexual revictimization was partially mediated by
      sexual self-esteem, sexual concerns, and high-risk sexual behaviors. This study
      emphasizes the need for further research on child maltreatment, revictimization,
      and women's sexual adjustment.

PMID- 16595848
TI  - Exploring consensus in practice with youth who are sexually abusive: findings
      from a Delphi study of practitioner views in the United Kingdom and the Republic
      of Ireland.
AB  - This article presents the findings of a study exploring current levels of
      consensus among practitioners in the United Kingdom (UK) and the Republic of
      Ireland (ROI) about good practice in relation to youth who are sexually abusive.
      A three-stage Delphi procedure was used to survey the views of 78 practitioners,
      experienced in this field, on a range of matters relating to preferred responses
      to this population. The exercise indicated high levels of agreement that youth
      who are sexually abusive should be seen as a group clinically distinct from adult
      sex offenders and that all of their developmental needs, and their problematic
      behavior, should be targeted in intervention. A strong level of consensus was
      found among respondents about the goals and content of ideal practice with this
      user group, although there was less consensus about the theoretical models that
      should underpin practice.

PMID- 16595849
TI  - Discipline practices among biological and foster parents.
AB  - In a sample of 124 parents (62 pairs of biological and foster parents) of
      children who were maltreated (M age = 6.2 years), this study compared self
      reports of discipline practices between biological and foster parents toward a
      target child and explored the role of child, parent, and foster care ecology
      factors on discipline practices. Controlling for parental age, psychological
      distress, and marital status, biological and foster parents reported using
      similar levels of positive, appropriate, and harsh discipline. For biological and
      foster parents, child characteristics (being female, younger, and having more
      conduct problems) were associated with parental self-reports of less effective
      discipline. The study also found a positive association between parent-to-parent
      cooperation and effective discipline. These findings suggest that parenting
      interventions may need to move beyond simple presumption of deficits in parenting
      knowledge, and that children could benefit from enhancement of supportive
      relationships between biological and foster parents involved in the foster care
      system.

PMID- 16595850
TI  - Racial variation in self-labeled child abuse and associated internalizing
      symptoms among adolescents who are high risk.
AB  - One thousand and ten Non-Hispanic White, African American, Hispanic, and Asian
      Pacific Islander youth who were high risk and receiving public sector services
      were interviewed regarding history of child emotional and physical abuse and
      current internalizing symptoms. The study examined whether race moderated the
      association between adolescents' reports of specific parent behaviors and their
      self-labeling as victims of abuse. The study also examined whether reports of
      parental behaviors or self-labeled abuse better predicted internalizing symptoms,
      and whether these associations differed by race. When reporting punitive parent
      behavior, Non-Hispanic White youth were more likely to describe themselves as
      abused compared to Asian Pacific Islanders. Reported punitive parental behaviors
      accounted for more variance in internalizing symptoms than did self-labeled
      abuse. Reports of parent behaviors were more strongly related to concurrent
      internalizing symptoms among ethnic minority youth than among Non-Hispanic White
      youth. Results are discussed in the context of cultural competence in
      identification of child abuse.

PMID- 16595851
TI  - Funding of child abuse evaluations: survey of child abuse evaluation programs.
AB  - This article delineates the current fiscal management and reimbursement for child
      abuse examinations. These financial issues are high priority for child abuse
      programs because most programs lack the revenues to meet the demands for service,
      education, advocacy and research. Programs may share medical protocols and
      standards but have yet to share management solutions. The authors present the
      administrative details of 75 child abuse evaluation programs and highlight
      innovative approaches to increase funding and stabilize the funding for the
      programs. They present information on billing, contracts, costs of care, and
      state-based initiatives that can be reproduced by other programs and states.

PMID- 16595852
TI  - Foster children's diurnal production of cortisol: an exploratory study.
AB  - Young children in foster care have often experienced inadequate early care and
      separations from caregivers. Preclinical studies suggest that early inadequate
      care and separations are associated with long-term changes in regulation of the
      hypothalamic-pituitary-adrenal (HPA) axis. In this study, the daytime pattern of
      cortisol production was examined among 55 young children who had been placed into
      foster care and 104 children who had not. Saliva samples were taken at wake-up,
      in the afternoon, and bedtime for 2 days. Average salivary cortisol values for
      each time of day were computed. A group (foster vs. comparison) time (morning,
      afternoon, night) interaction emerged, reflecting less decline in levels across
      the day for foster than comparison children. Daytime patterns were categorized as
      typical, low, or high. Children who had been in foster care had higher incidences
      of atypical patterns of cortisol production than children who had not. These
      differences suggest that conditions associated with foster care interfere with
      children's ability to regulate neuroendocrine functioning.

PMID- 16595853
TI  - Effects of DGAT1 deficiency on energy and glucose metabolism are independent of
      adiponectin.
AB  - Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), an enzyme that
      catalyzes the terminal step in triacylglycerol synthesis, have enhanced insulin
      sensitivity and are protected from obesity, a result of increased energy
      expenditure. In these mice, factors derived from white adipose tissue (WAT)
      contribute to the systemic changes in metabolism. One such factor, adiponectin,
      increases fatty acid oxidation and enhances insulin sensitivity. To test the
      hypothesis that adiponectin is required for the altered energy and glucose
      metabolism in DGAT1-deficient mice, we generated adiponectin-deficient mice and
      introduced adiponectin deficiency into DGAT1-deficient mice by genetic crosses.
      Although adiponectin-deficient mice fed a high-fat diet were heavier, exhibited
      worse glucose tolerance, and had more hepatic triacylglycerol accumulation than
      wild-type controls, mice lacking both DGAT1 and adiponectin, like DGAT1-deficient
      mice, were protected from diet-induced obesity, glucose intolerance, and hepatic
      steatosis. These findings indicate that adiponectin is required for normal
      energy, glucose, and lipid metabolism but that the metabolic changes induced by
      DGAT1-deficient WAT are independent of adiponectin and are likely due to other
      WAT-derived factors. Our findings also suggest that the pharmacological
      inhibition of DGAT1 may be useful for treating human obesity and insulin
      resistance associated with low circulating adiponectin levels.

PMID- 16595854
TI  - UCP1 is essential for adaptive adrenergic nonshivering thermogenesis.
AB  - Participation of brown adipose tissue [through the action of the uncoupling
      protein-1 (UCP1)] in adaptive adrenergic nonshivering thermogenesis is
      recognized, but the existence of a response to adrenergic stimulation in UCP1
      ablated mice implies that a mechanism for an alternative adaptive adrenergic
      thermogenesis may exist. Here, we have used UCP1-ablated mice to examine the
      existence of an alternative adaptive adrenergic nonshivering thermogenesis,
      examined as the oxygen consumption response to systemically injected
      norepinephrine into anesthetized or conscious mice acclimated to different
      temperatures. We confirm that UCP1-dependent adrenergic nonshivering
      thermogenesis is adaptive, but we demonstrate that the adrenergic UCP1
      independent thermogenesis is not recruitable by cold acclimation. Thus, at least
      in the mouse, no other proteins or enzymatic pathways exist that can participate
      in or with time take over the UCP1 mediation of adaptive adrenergic nonshivering
      thermogenesis, even in the total absence of UCP1. UCP1 is thus the only protein
      capable of mediating cold acclimation-recruited adaptive adrenergic nonshivering
      thermogenesis.

PMID- 16595856
TI  - Mapping heritability and molecular genetic associations with cortical features
      using probabilistic brain atlases: methods and applications to schizophrenia.
AB  - There is an urgent need to decipher the complex nature of genotype-phenotype
      relationships within the multiple dimensions of brain structure and function that
      are compromised in neuropsychiatric syndromes such as schizophrenia. Doing so
      requires sophisticated methodologies to represent population variability in
      neural traits and to probe their heritable and molecular genetic bases. We have
      recently developed and applied computational algorithms to map the heritability
      of, as well as genetic linkage and association to, neural features encoded using
      brain imaging in the context of three-dimensional (3D), populationbased,
      statistical brain atlases. One set of algorithms builds on our prior work using
      classical twin study methods to estimate heritability by fitting biometrical
      models for additive genetic, unique, and common environmental influences. Another
      set of algorithms performs regression-based (Haseman-Elston) identical-bydescent
      linkage analysis and genetic association analysis of DNA polymorphisms in
      relation to neural traits of interest in the same 3D population-based brain atlas
      format. We demonstrate these approaches using samples of healthy monozygotic (MZ)
      and dizygotic (DZ) twin pairs, as well as MZ and DZ twin pairs discordant for
      schizophrenia, but the methods can be generalized to other classes of relatives
      and to other diseases. The results confirm prior evidence of genetic influences
      on gray matter density in frontal brain regions. They also provide converging
      evidence that the chromosome 1q42 region is relevant to schizophrenia by
      demonstrating linkage and association of markers of the Transelin-Associated
      Factor-X and Disrupted-In- Schizophrenia-1 genes with prefrontal cortical gray
      matter deficits in twins discordant for schizophrenia.

PMID- 16595859
TI  - High-resolution large-scale mosaic imaging using multiphoton microscopy to
      characterize transgenic mouse models of human neurological disorders.
AB  - The thorough characterization of transgenic mouse models of human central nervous
      system diseases is a necessary step in realizing the full benefit of using animal
      models to investigate disease processes and potential therapeutics. Because of
      the labor- and resource-intensive nature of high-resolution imaging, detailed
      investigation of possible structural or biochemical alterations in brain sections
      has typically focused on specific regions of interest as determined by the
      researcher a priori. For example, Parkinson's disease researchers often focus
      imaging on regions of the brain expected to exhibit pathology such as the
      substantia nigra and striatum. Because of limitations in acquiring and storing
      high-resolution imaging data, additional data contained in the specimen is not
      usually acquired or disseminated/reported to the research community. Here we
      present a method of imaging large regions of brain at close to the resolution
      limit of light microscopy using a mosaic imaging technique in conjunction with
      multiphoton microscopy. These maps are being used to characterize several
      genetically modified animal models of neurological disease by filling the
      information "gap" among techniques such as magnetic resonance imaging and
      electron microscopic analysis.

PMID- 16595858
TI  - Imaging genomics applied to anxiety, stress response, and resiliency.
AB  - Anxiety and stress response/resiliency are heritable traits central to the
      etiology of multiple psychiatric diseases, but efforts to identify genetic
      variation influencing this broad domain of neurobiological function are hampered
      by the coarseness of the phenotypic measures and the effects of environmental
      factors. Neuroimaging offers a powerful approach for assessing functional
      neuronal activity. Neurophysiological measures can serve as intermediate
      phenotypes more directly linked to small gene effects, compared with behavioral
      end points of neural dysfunction. Imaging genomics is a relatively new research
      area that is concerned with linking functional gene variants and brain
      information processing. Here, we will focus on processes affected by anxiety and
      stress. Neuroimaging has been combined with genetic analysis to reveal genetic
      effects of functional variants of the serotonin transporter (5-HTT) and catechol
      O-methyltransferase (COMT) genes on brain response to stressful stimuli. The low
      expressing allele of the 5-HTT promoter polymorphism (HTTLPR) is associated with
      anxiety and with greater amygdala and other regional responses to emotional. The
      COMT Met158 allele leads to lower COMT activity and has also been associated with
      anxiety, and the effect of this gene is apparently additive with HTTLPR.
      Individuals with Met158 genotypes are more sensitive to pain stress and, as shown
      by C11 Carfentanil imaging, have diminished ability to upregulate opioid release
      after pain/stress. These results suggest that functional variants of 5-HTT and
      COMT impact brain functions involved in stress and anxiety.

PMID- 16595861
TI  - Bayesian variable selection for gene expression modeling with regulatory motif
      binding sites in neuroinflammatory events.
AB  - Multiple transcription factors (TFs) coordinately control transcriptional
      regulation of genes in eukaryotes. Although numerous computational methods focus
      on the identification of individual TF-binding sites (TFBSs), very few consider
      the interdependence among these sites. In this article, we studied the
      relationship between TFBSs and microarray gene expression levels using both
      family-wise and memberspecific motifs, under various combination of regression
      models with Bayesian variable selection, as well as motif scoring and sharing
      conditions, in order to account for the coordination complexity of transcription
      regulation. We proposed a three-step approach to model the relationship. In the
      first step, we preprocessed microarray data and used p-values and expression
      ratios to preselect upregulated and downregulated genes. The second step aimed to
      identify and score individual TFBSs within DNA sequence of each gene. A method
      based on the degree of similarity and the number of TFBSs was employed to
      calculate the score of each TFBS in each gene sequence. In the last step, linear
      regression and probit regression were used to build a predictive model of gene
      expression outcomes using these TFBSs as predictors. Given a certain number of
      predictors to be used, a full search of all possible predictor sets is usually
      combinatorially prohibitive. Therefore, this article considered the Bayesian
      variable selection for prediction using either of the regression models. The
      Bayesian variable selection has been applied in the context of gene selection,
      missing value estimation, and regulatory motif identification. In our modeling,
      the regressor was approximated as a linear combination of the TFBSs and a Gibbs
      sampler was employed to find the strongest TFBSs. We applied these regression
      models with the Bayesian variable selection on spinal cord injury gene expression
      data set. These TFs demonstrated intricate regulatory roles either as a family or
      as individual members in neuroinflammatory events. Our analysis can be applied to
      create plausible hypotheses for combinatorial regulation by TFBSs and avoiding
      false-positive candidates in the modeling process at the same time. Such a
      systematic approach provides the possibility to dissect transcription regulation,
      from a more comprehensive perspective, through which phenotypical events at
      cellular and tissue levels are moved forward by molecular events at gene
      transcription and translation levels.

PMID- 16595860
TI  - Mutual information-based feature selection in studying perturbation of dendritic
      structure caused by TSC2 inactivation.
AB  - In this study, the effect of protein Tuberous sclerosis 2 (TSC2) on the dendritic
      spine density and length was demonstrated by using TSC2-RNAinactivation. In
      addition, the role of rapamycin, an antagonist of the molecular target of
      rapamycin, in the morphological changes of spine caused by TSC2 silencing was
      investigated. The features were extracted from highresolution three-dimensional
      image stacks collected by two-photon laser scanning microscopy of green
      fluorescing pyramidal cells expressing TSC2-RNA interference (RNAi), or TSC2-RNAi
      and rapamycin treatment in rat hippocampal slice cultures. We proposed to apply
      the lognormal distribution method for feature extraction. The extracted features
      of three cases under investigation, namely, (1) green-fluorescent protein GFP vs
      TSC2-RNAi, (2) GFP vs TSC2-RNAi and rapamycin, and (3) TSC2-RNAi vs TSC2-RNAi and
      rapamycin, were analyzed by mutual information-based feature selection and
      evaluated by three classifiers, K-nearest neighbor, Perceptron, and two-layer
      neural networks. The results showed that both the spine density and length have
      significant morphological changes after TSC2-RNAi treatment. However, rapamycin
      treatment could reverse the effect of TSC2-RNAi on spine length but not on spine
      density. These results are consistent with the results reported in the scientific
      literature. Finally, we explored the application of pattern recognition method in
      a small sample with richer feature properties, namely bootstrap mutual
      information estimation and a mutual information- based feature selection method.

PMID- 16595857
TI  - Imaging phenotypes and genotypes in schizophrenia.
AB  - Schizophrenia is associated with subtle structural and functional brain
      abnormalities. Both recent and classical data suggest that it is a heterogeneous
      disorder that is clearly heritable. The cause and course of schizophrenia are
      poorly understood, and classical categories of clinical symptoms have not been
      particularly useful in identifying its pathophysiology or predicting its
      treatment. The possible genetic risk factors for schizophrenia are numerous;
      however, the connection between the genotype and the time-course, or the
      multifaceted symptoms of the disease, has yet to be established. Brain imaging
      methods that study the structure or function of the cortical and subcortical
      regions have also identified distinct patterns that distinguish schizophrenics
      from controls, and that may identify meaningful subtypes of schizophrenia. The
      predictive relationship between these imaging phenotypes and disease
      characteristics such as treatment response is only beginning to be revealed. The
      emergence of the field of imaging genetics, combining genetic, and neuroimaging
      data, holds much promise for the deeper understanding and improved treatment of
      diseases such as schizophrenia. In this article we review some of the key
      findings in imaging phenotyping and genotyping of schizophrenia, and the initial
      endeavors at their combination into more meaningful and predictive patterns, or
      endophenotypes identifying the relationships among clinical symptoms, course,
      genes, and the underlying pathophysiology.

PMID- 16595862
TI  - Dynamic phenotypes: time series analysis techniques for characterizing neuronal
      and behavioral dynamics.
AB  - We consider quantitative measures of behavioral and neuronal dynamics as a means
      of characterizing phenotypes. Such measures are important from a scientific
      perspective; because understanding brain function is contingent on understanding
      the link between the dynamics of the nervous system and behavioral dynamics. They
      are also important from a biomedical perspective because they provide a contrast
      to purely psychological characterizations of phenotype or characterizations via
      static brain images or maps, and are a potential means for differential diagnoses
      of neuropsychiatric illnesses. After a brief presentation of background work and
      some current advances, we suggest that more attention needs to be paid to dynamic
      characterizations of phenotypes. We will discuss some of the relevant time series
      analysis tools.

PMID- 16595868
TI  - Magic with moulds: meiotic and mitotic crossing over in Neurospora inversions and
      duplications.

PMID- 16595869
TI  - Ancient Indian roots?

PMID- 16595870
TI  - Erwin Bunning (1906-1990): a centennial homage.

PMID- 16595871
TI  - Living in a physical world VI. Gravity and life in the air.

PMID- 16595872
TI  - What history tells us IV. Ciliates as models . . . of what?

PMID- 16595873
TI  - Allele-specific suppression of the temperature sensitivity of fitA/fitB mutants
      of Escherichia coli by a new mutation (fitC4): isolation, characterization and
      its implications in transcription control.
AB  - The temperature sensitive transcription defective mutant of Escherichia coli
      originally called fitA76 has been shown to harbour two missense mutations namely
      pheS5 and fit95. In order to obtain a suppressor of fitA76, possibly mapping in
      rpoD locus, a Ts+ derivative (JV4) was isolated from a fitA76 mutant. It was
      found that JV4 neither harbours the lesions present in the original fitA76 nor a
      suppressor that maps in or near rpoD. We show that JV4 harbours a modified form
      of fitA76 (designated fitA76*) together with its suppressor. The results
      presented here indicate that the fit95 lesion is intact in the fitA76* mutant and
      the modification should be at the position of pheS5. Based on the cotransduction
      of the suppressor mutation and/or its wild type allele with pps, aroD and zdj
      3124::Tn10 kan we have mapped its location to 39.01 min on the E. coli
      chromosome. We tentatively designate the locus defined by this new extragenic
      suppressor as fitC and the suppressor allele as fitC4. While fitC4 could suppress
      the Ts phenotype of fitA76* present in JV4, it fails to suppress the Ts phenotype
      of the original fitA76 mutant (harbouring pheS5 and fit95). Also fitC4 could
      suppress the Ts phenotype of a strain harbouring only pheS5. Interestingly, the
      fitC4 Ts phenotype could also be suppressed by fit95. The pattern of decay of
      pulse labelled RNA in the strains harbouring fitC4 and the fitA76* resembles that
      of the original fitA76 mutant implying a transcription defect similar to that of
      fitA76 in both these mutants. The implications of these findings with special
      reference to transcription control by Fit factors in vivo are discussed.

PMID- 16595874
TI  - Coat protein sequence shows that Cucumber mosaic virus isolate from geraniums
      (Pelargonium spp.) belongs to subgroup II.
AB  - A viral disease was identified on geraniums (Pelargonium spp.) grown in a
      greenhouse at the Institute of Himalayan Bioresource Technology (IHBT), Palampur,
      exhibiting mild mottling and stunting. The causal virus (Cucumber mosaic virus,
      CMV) was identified and characterized on the basis of host range, aphid
      transmission, enzyme linked immunosorbent assay (ELISA), DNA-RNA hybridization
      and reverse transcription polymerase chain reaction (RT-PCR). A complete coat
      protein (CP) gene was amplified using degenerate primers and sequenced. The CP
      gene showed nucleotide and amino acid homology up to 97%-98% and 96%-99%,
      respectively with the sequences of CMV subgroup II. The CP gene also showed
      homologies of 75%-97% in nucleotide and 77%-96% in amino acid with the CMV Indian
      isolates infecting various crops. On the basis of sequence homology, it was
      concluded that CMV-infecting geraniums in India belong to subgroup II.

PMID- 16595875
TI  - Age-related changes of structures in cerebellar cortex of cat.
AB  - We studied the structures of the cerebellar cortex of young adult and old cats
      for age-related changes, which were statistically analysed. Nissl staining was
      used to visualize the cortical neurons. The immunohistochemical method was used
      to display glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes
      and neurofilament-immunoreactive (NF-IR) neurons. Under the microscope, the
      thickness of the cerebellar cortex was measured; and the density of neurons in
      all the layers as well as that of GFAP-IR cells in the granular layer was
      analysed. Compared with young adult cats, the thickness of the molecular layer
      and total cerebellar cortex was significantly decreased in old cats, and that of
      the granular layer increased. The density of neurons in each layer was
      significantly lower in old cats than in young adult ones. Astrocytes in old cats
      were significantly denser than in young adult ones, and accom-panied by evident
      hypertrophy of the cell bodies and enhanced immunoreaction of GFAP substance.
      Purkinje cells (PCs) in old cats showed much fewer NF-IR dendrites than those in
      young adults. The above findings indicate a loss of neurons and decrease in the
      number of dendrites of the PCs in the aged cerebellar cortex, which might
      underlie the functional decline of afferent efficacy and information integration
      in the senescent cerebellum. An age-dependent enhancement of activity of the
      astrocytes may exert a protective effect on neurons in the aged cerebellum.

PMID- 16595876
TI  - Ni2+-uptake in Pseudomonas putida strain S4: a possible role of Mg2+-uptake pump.
AB  - Essential metal ion homeostasis is based on regulated uptake of metal ions, both
      during its scarcity and abundance. Pseudomonas putida strain S4, a multimetal
      resistant bacterium, was employed to investigate Ni(2+) entry into cells. It was
      observed that Mg(2+) regulates the entry of Ni(2+) and by this plays a protective
      role to minimize Ni(2+) toxicity in this strain. This protection was evident in
      both growth as well as viability. Intracellular accumulation of Ni(2+) varied in
      accordance with Mg(2+) concentrations in the medium. It was hypothesized that
      Ni(2+) enters the cell using a broad Mg(2+) pump, i.e. the CorA system, as the
      CorA inhibitor, i.e. Co(III) Hex, also inhibits Ni 2+ uptake. This led to the
      inference that Mg(2+)-based protection was basically due to competitive
      inhibition of Ni(2+) uptake. We also show that Zn(2+) can further regulate the
      entry of Ni(2+).

PMID- 16595877
TI  - Candidate genes for drought tolerance and improved productivity in rice (Oryza
      sativa L.).
AB  - Candidate genes are sequenced genes of known biological action involved in the
      development or physiology of a trait. Twenty-one putative candidate genes were
      designed after an exhaustive search in the public databases along with an
      elaborate literature survey for candidate gene products and/or regulatory
      sequences associated with enhanced drought resistance. The downloaded sequences
      were then used to design primers considering the flanking sequences as well.
      Polymerase chain reaction (PCR) performed on 10 diverse cultivars that involved
      Japonica, Indica and local accessions, revealed 12 polymorphic candidate genes.
      Seven polymorphic candidate genes were then utilized to genotype 148 individuals
      of CT9993 x IR62266 doubled haploid (DH) mapping population. The segregation data
      were tested for deviation from the expected Mendelian ratio (1:1) using a Chi
      square test (less than 1%). Based on this, four candidate genes were assessed to
      be significant and the remaining three, as non-significant. All the significant
      candidate genes were biased towards CT9993, the female parent in the DH mapping
      population. Single-marker analysis strongly associated (less than 1%) them to
      different traits under both well-watered and low-moisture stress conditions. Two
      candidate genes, EXP15 and EXP13, were found to be associated with root number
      and silicon content in the stem respectively, under both well-watered and low
      moisture stress conditions.

PMID- 16595878
TI  - Lyriform slit sense organs on the pedipalps and spinnerets of spiders.
AB  - Lyriform slits sense organs (LSSO) are a precise assembly of stress detecting
      cuticular slit sensilla found on the appendages of arachnids. While these
      structures on the legs of the wandering spider Cupennius salei are well studied
      in terms of morphology, function and contribution to behaviour, their
      distribution on pedipalps and spinnerets of spiders is not well explored. A study
      was therefore carried out to observe the distribution of LSSO on pedipalps and
      spinnerets of some spider species. Haplogyne spiders belonging to family
      Pholcidae have a simple complement of LSSOs represented by one or two LSSOs on
      their femur. The entelegyne spiders possess a complex assembly of LSSOs on the
      distal segments of their pedipalps. Various types of LSSOs are found on the
      pedipalps indicating a capacity for analysis of complex cuticular stress. It is
      suggested that the complexity of LSSOs on pedipalps of entel-egyne spiders
      relates to courtship and spermatophore transfer and may help in reproductive
      isolation. Lack of LSSOs on the distal segments of pedipalps leads us to infer
      that unlike legs, pedipalps are less likely to receive vibratory input through
      their distal segments. Spinnerets have a relatively simple complement of LSSOs.
      One LSSO is found only on anterior spinnerets and it is a common feature observed
      among spiders, irrespective of the variations in web building behaviour. The orb
      weaving araneid Argiope pulchella, however, has two LSSOs on the anterior
      spinneret. As non-web builders and orb weavers do not differ markedly in terms of
      LSSOs on the spinnerets and LSSOs are simple in nature (type A), it is likely
      that spinning and weaving are not largely regulated by sensory input from LSSOs
      on the spinnerets.

PMID- 16595879
TI  - Natural recovery of steppe vegetation on vehicle tracks in central Mongolia.
AB  - Steppe desertification due to vehicle travel is a severe environmental issue in
      Mongolia. We studied natural vegetation recovery on abandoned vehicle tracks in
      the central Mongolia steppe through vegetation surveys and stable isotopic
      techniques. The following issues were addressed: (i) invasion of pioneering plant
      species, (ii) alteration of soil surface features, and (iii) contribution of
      revegetated plants to soil organic matter (SOM). The pioneering plant species
      that firstly invaded the abandoned tracks are those that could germinate, root
      and survive in the compacted track surface. Salsola collina is one of these
      candidate plants. Due to revegetation, soil surface hardness was reduced. With
      the improvement of surface microenvironmental conditions, other plants began to
      colonize and establish; con-comitantly species richness and species diversity
      increased. Carbon isotope ratios of SOM at the top surface layer indicated that
      C4 -derived carbon contributed more to SOM in the early phase of recovery and
      decreased with further recovery.

PMID- 16595880
TI  - Phylogenetic tests of distribution patterns in South Asia: towards an integrative
      approach.
AB  - The last four decades have seen an increasing integration of phylogenetics and
      biogeography. However, a dearth of phylogenetic studies has precluded such
      biogeographic analyses in South Asia until recently. Noting the increase in
      phylogenetic research and interest in phylogenetic biogeography in the region, we
      outline an integrative framework for studying taxon distribution patterns. While
      doing so, we pay particular attention to challenges posed by the complex
      geological and ecological history of the region, and the differences in
      distribution across taxonomic groups. We outline and compare three widely used
      phylogenetic biogeographic approaches: topology-based methods (TBMs), pattern
      based methods (PBMs) and event-based methods (EBMs). TBMs lack a quantitative
      framework and utilize only part of the available phylogenetic information. Hence,
      they are mainly suited for preliminary enquiries. Both PBMs and EBMs have a
      quantitative framework, but we consider the latter to be particularly suited to
      the South Asian context since they consider multiple biogeographic processes
      explicitly, and can accommodate a reticulated history of areas. As an
      illustration, we present a biogeographic analysis of endemic Sri Lankan agamid
      lizards. The results provide insights into the relative importance of multiple
      processes and specific zones in the radiation of two speciose lizard clades.

PMID- 16595881
TI  - Record of Lower Gondwana megafloral assemblage from Lower Kamthi Formation of Ib
      River Coalfield, Orissa, India.
AB  - Recent investigations carried out in the Ib River Coalfield, Mahanadi Master
      Basin, Orissa, identified some fossilif-erous beds in the Lower Gondwana
      deposits. Two exposures of the Lower Kamthi Formation yielded diverse and
      abundant plant remains, which include Neomariopteris, Vertebraria, and a scale
      leaf along with 14 Glossopteris species otherwise mapped as Barren Measures and
      Upper Kamthi formations. Glossopteris indica dominates the flora (22.78%)
      followed by G. communis (17.72%) and G. browniana (13.92%). Based on megafloral
      assemblages, different beds exposed at Gopalpur and Laxamanpur Pahar are assigned
      here to the Lower Kamthi Formation (Late Permian). The floristic composition
      suggests that a warm and humid climate prevailed during the Late Permian. The
      status of the Kamthi Formation in the Ib River Coalfield has been redefined in
      the present study.

PMID- 16595882
TI  - A model for the dynamics of human weight cycling.
AB  - The resolution to lose weight by cognitive restraint of nutritional intake often
      leads to repeated bouts of weight loss and regain, a phenomenon known as weight
      cycling or "yo-yo dieting". A simple mathematical model for weight cycling is
      presented. The model is based on a feedback of psychological nature by which a
      subject decides to reduce dietary intake once a threshold weight is exceeded. The
      analysis of the model indicates that sustained oscillations in body weight occur
      in a parameter range bounded by critical values. Only outside this range can body
      weight reach a stable steady state. The model provides a theoretical framework
      that captures key facets of weight cycling and suggests ways to control the
      phenomenon. The view that weight cycling represents self-sustained oscillations
      has indeed specific implications. In dynamical terms, to bring weight cycling to
      an end, parameter values should change in such a way as to induce the transition
      of body weight from sustained oscillations around an unstable steady state to a
      stable steady state. Maintaining weight under a critical value should prevent
      weight cycling and allow body weight to stabilize below the oscillatory range.

PMID- 16595885
TI  - Looking back, looking beyond: revisiting the ethics of genome generation.
AB  - This paper will explore some of the ethical imperatives that have shaped
      strategic and policy frameworks for the use of new genetic technologies and how
      these play a role in shaping the nature of research and changing attitudes; with
      an attempt to conceptualize some theories of genetic determinism. I analyse why
      there is a need to put bioethical principles within a theoretical framework in
      the context of new technologies, and how, by doing so, their practical
      applications for agriculture, environment medicine and health care can be
      legitimized. There are several theories in favour of and against the use of
      genetic technologies that focus on genes and their role in our existence. In
      particular the theory of geneticisation is commonly debated. It highlights the
      conflicting interests of science, society and industry in harnessing genetic
      knowledge when the use of such knowledge could challenge ethical principles.
      Critics call it a 'reductionist' approach, based on arguments that are narrowed
      down to genes, often ignoring other factors including biological, social and
      moral ones. A parallel theory is that there is something special about genes, and
      it is this "genetic exceptionalism" that creates hopes and myths. Either way, the
      challenging task is to develop a common ground for understanding the importance
      of ethical sensitivities. As research agendas become more complex, ethical
      paradigms will need to be more influential. New principles are needed to answer
      the complexities of ethical issues as complex technologies develop. This paper
      reflects on global ethical principles and the tensions between ethical principles
      in legitimizing genetic technologies at the social and governance level.

PMID- 16595884
TI  - Mechanism of bacterial adaptation to low temperature.
AB  - Survival of bacteria at low temperatures provokes scientific interest because of
      several reasons. Investigations in this area promise insight into one of the
      mysteries of life science - namely, how the machinery of life operates at extreme
      environments. Knowledge obtained from these studies is likely to be useful in
      controlling pathogenic bacteria, which survive and thrive in cold-stored food
      materials. The outcome of these studies may also help us to explore the
      possibilities of existence of life in distant frozen planets and their
      satellites.

PMID- 16595886
TI  - Low viscous separation media for genomics and proteomics analysis on microchip
      electrophoresis system.
AB  - Microchip electrophoresis has widely grown during the past few years, and it has
      showed a significant result as a strong separation tool for genomic as well as
      proteomic researches. To enhance and expand the role of microchip
      electrophoresis, several studies have been proposed especially for the low
      viscous separation media, which is an important factor for the success of
      microchip with its narrow separation channels. In this paper we show an overview
      for the done researches in the field of low viscous media developed for the use
      in microchip electrophoresis. For genomic separation studies polyhydroxy
      additives have been used enhance the separation of DNA at low polymer
      concentration of HPMC (Hydroxypropylmethyl cellulose) which could keep the
      viscosity low. Mixtures of poly(ethylene oxide) as well as Hydroxyporpyl
      cellulose have been successfully introduced for chip separation. Furthermore high
      molecular mass polyacrylamides at low concentrations have been studied for DNA
      separation. A mixture of polymer nanoparticle with conventional polymers could
      show a better resolution for DNA at low concentration of the polymer. For the
      proteomic field isoelectric focusing on chip has been well overviewed since it is
      the most viscous separation media which is well used for the protein separation.
      The different types of isoelectric focusing such as the ampholyte-free type, the
      thermal type as well as the ampholyte-depended type have been introduced in this
      paper. Isoelectric focusing on chip with its combination with sodium dodecyl
      sulfate (SDS) page or free solution could give a better separation. Several
      application for this low viscous separation medias for either genomic or
      proteomic could clearly show the importance of this field.

PMID- 16595887
TI  - Effects of 2-methyl-1,4-naphtoquinone (menadione) on cellular signaling in RBL
      2H3 cells.
AB  - Reactive oxygen species (ROS) are produced in various cells and affect many
      biologic processes. In this study, we examined the effects of 2-methyl-1,4
      naphtoquinone (menadione; vitamin K3) on signal transduction in mast cells.
      Several lines of evidence suggest that H2O2 affects the antigen-induced responses
      in mast cells but its mechanism is not clearly understood. Unlike H2O2, menadione
      produces ROS only inside cells. Thus, it is possible to investigate the effects
      of ROS produced intracellularly. Pretreatment of mast cells (RBL-2H3) with
      menadione inhibited exocytotic secretion (degranulation) induced by antigen
      stimulation dose dependently. Menadione also inhibited the intracellular Ca2+
      increase induced by antigen stimulation. Menadione did not inhibit the Ca2+
      increase due to Ca2+ release from the intracellular calcium store in the absence
      of extracellular Ca2+, but inhibited the Ca2+ influx from the extracellular
      medium. These results suggest that reactive oxygen generated inside RBL cells by
      menadione inhibited degranulation by decreasing Ca2+ influx through the store
      operated Ca2+ channel on the plasma membrane.

PMID- 16595888
TI  - Simultaneous determination of the contents of three stilbene oligomers in
      Caragana sinica collected in different seasons using an improved HPLC method.
AB  - The objectives of this research were to determine simultaneously the contents of
      two stilbene tetramers, carasinol B (1) and kobophenol A (2), and one stilbene
      trimer, (+)-alpha-viniferin (3), in the roots, tubers, and leaves of Caragana
      sinica in various seasons. A HPLC method has been developed for efficiently
      quantifying the three analytes in the plant. Using this method, different samples
      of Caragana sinica were evaluated. The results showed that the contents of 1, 2,
      and 3 in the roots were much higher than those in the tubers, and the contents of
      stilbene tetramers were maximal in winter while the contents of the stilbene
      trimer were maximal in summer. Compounds 1, 2, and 3 could not be detected in the
      flowers of Caragana sinica in our detection ranges.

PMID- 16595883
TI  - The ubiquitin-proteasome system.
AB  - The 2004 Nobel Prize in chemistry for the discovery of protein ubiquitination has
      led to the recognition of cellular proteolysis as a central area of research in
      biology. Eukaryotic proteins targeted for degradation by this pathway are first
      'tagged' by multimers of a protein known as ubiquitin and are later proteolyzed
      by a giant enzyme known as the proteasome. This article recounts the key
      observations that led to the discovery of ubiquitin-proteasome system (UPS). In
      addition, different aspects of proteasome biology are highlighted. Finally, some
      key roles of the UPS in different areas of biology and the use of inhibitors of
      this pathway as possible drug targets are discussed.

PMID- 16595889
TI  - Influence of cholesterol composition on the association of serum mannan-binding
      proteins with mannosylated liposomes.
AB  - In our previous studies, serum mannan-binding protein (MBP) accelerated the
      uptake by cultured macrophages. The present study was initiated to investigate
      the kinetics of molecular interaction between mannosylated liposomes and MBP in
      more details and the effects of lipid composition on the interaction. The
      analysis was carried out by surface plasmon spectroscopy (SPR) methods, using
      rabbit serum MBP isolated by affinity chromatography. In SPR studies, neither
      conventional liposomes nor galactosylated liposomes indicated any interaction,
      but each mannosylated liposomes had a high response signal corresponding to
      molecular interaction with immobilized MBP. Association of mannosylated liposomes
      to serum MBP was not dependent on the lipid composition, suggesting a diffusion
      controlled association. Dissociation of the mannosylated liposomes from serum MBP
      was extremely slow. DSPC/Chol/Man-C4-Chol (90 : 5 : 5, molar ratio) exhibited a
      slower dissociation rate than DSPC/Chol/Man-C4-Chol (60 : 35 : 5). Clustering of
      mannose residues on liposomal surfaces might be important in determining the
      binding affinity of mannosylated liposomes with MBP.

PMID- 16595890
TI  - Prophylactic effects of ajoene on cerebral injury in stroke-prone spontaneously
      hypertensive rats (SHRSP).
AB  - As part of a basic study on the prevention of cerebral injury, ajoene (0.5 mg/d)
      and oil-macerated garlic extract (OMGE, containing 0.5 mg ajoene/d) were
      administrated to stroke-prone spontaneously hypertensive rats (SHRSP) among 8
      weeks from 9 weeks of age. In the control group, 3 of 10 rats died (30%), whereas
      all SHRSP treated by ajoene or OMGE survived. Our results suggested that ajoene
      and OMGE-treatment reduced the mortality and cerebral injury in SHRSP. The levels
      of thiobarbituric acid reactive substance (TBARS) and the enzymatic activities of
      glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) in
      the serum of stroke stage of SHRSP were measured. The results obtained were as
      follows; the TBARS level of the ajoene and OMGE-treated groups were lower than
      those of control groups. On the other hand, the GSH-Px and SOD activities of the
      ajoene and OMGE-treated groups were higher. Our results suggested that ajoene and
      OMGE were capable of having prophylactic effects on cerebral injury in SHRSP.

PMID- 16595891
TI  - Berberry extract reduces neuronal damage and N-Methyl-D-aspartate receptor 1
      immunoreactivity in the gerbil hippocampus after transient forebrain ischemia.
AB  - In the present study, we studied the neuroprotective effects of berberry extract
      (BE) against ischemic damage and the temporal and spatial alterations of N-methyl
      D-aspartate receptor type 1 (NR1) and NR2A/2B immunoreactivities in the gerbil
      hippocampal CA1 region after transient ischemia to examine anti-ischemic effects
      and its role in transient forebrain ischemia. In the vehicle-treated group, the
      percentage of cresyl violet positive pyramidal cells in the CA1 region was about
      11.4% compared to the sham-operated group 4 d after ischemic insult. BE showed
      neuroprotective effects against ischemic damage after ischemia-reperfusion. In
      the BE-treated groups, about 60-75% of CA1 pyramidal cells were stained with
      cresyl violet 4 d after ischemic insult. We observed the percentage of berberine
      (7.45+0.85 mg/g in BE) by HPLC, which is active ingredient of BE. NR1
      immunoreactivity in the stratum pyramidale of the CA1 region in the vehicle
      treated group was significantly increased at 30 min after transient forebrain
      ischemia, while at this time the NR1 immunoreactivity in the BE-treated groups
      was significantly low compared to the vehicle-treated group. The pattern of
      NR2A/B immunoreactivity in the stratum pyramidale of the BE-treated group and its
      protein levels were similar to that in the vehicle-treated group after ischemic
      insult. These results suggest that BE has potent neuroprotective effects against
      ischemic damage via the reduction of NR1 activity.

PMID- 16595892
TI  - Development of SCAR marker for discrimination of Artemisia princeps and A. argyi
      from other Artemisia herbs.
AB  - Some Artemisia herbs are used for medicinal purposes. In particular, A. princeps
      and A. argyi are classified as 'Aeyup' and are used as important medicinal
      material in traditional Korean medicine. On the other hand, A. capillaris and A.
      iwayomogi, which are classified as 'Injinho' and 'Haninjin', respectively, are
      used for other purposes distinct from those of 'Aeyup'. However, sometimes
      'Aeyup' is not clearly discriminated from 'Injinho' and/or 'Haninjin'.
      Furthermore, Artemisia capillaris and/or A. iwayomogi have been used in place of
      A. princeps and A. argyi. In this study, we developed an efficient method to
      discriminate A. argyi and A. princeps from other Artemisia plants. The RAPD
      (random amplified polymorphic DNA) method efficiently discriminated various
      Artemisia herbs. In particular, non-specific primer 329 (5'-GCG AAC CTC C-3'),
      which shows polymorphism among Artemisia herbs, amplified 838 bp products, which
      are specific to A. princeps and A. argyi only. Based on nucleotide sequence of
      the primer 329 product, we designed a Fb (5'-CAT CAA CCA TGG CTT ATC CT-3') and
      R7 (5'-GCG AAC CTC CCC ATT CCA-3') primer-set to amplify a 254 bp sized SCAR
      (sequence characterized amplified regions) marker, through which A. princeps and
      A. argyi can be efficiently discriminated from other Artemisia herbs,
      particularly, A. capillaris and A. iwayomogi.

PMID- 16595893
TI  - Anti-inflammatory effect of pitavastatin on NF-kappaB activated by TNF-alpha in
      hepatocellular carcinoma cells.
AB  - As nuclear factor-kappa B (NF-kappaB) is essential for promoting inflammation
      associated cancer, it is a potential target for cancer prevention in chronic
      inflammatory diseases. Here we examined the anti-inflammatory effect of
      pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitor, on NF-kappaB activated by TNF-alpha in hepatocellular carcinoma (HCC)
      cells. Western blot revealed that the treatment of Huh 7 cells with pitavastatin
      at 0.1 microM inhibited the nuclear expression of NF-kappaB p65 induced by TNF
      alpha. Furthermore, electrophoretic mobility shift assay showed that after the
      cells were incubated with pitavastatin alone or with pitavastatin and TNF-alpha
      for 24 h, pitavastatin significantly decreased the DNA binding activity of NF
      kappaB induced by TNF-alpha. Subsequently, luciferase assay revealed that
      pitavastatin suppressed the transcriptional activity of the NF-kappaB promoter,
      which was clearly related to the HMG-CoA reductase activity because the addition
      of mevalonic acid (MEV) elevated the TNF-alpha activity. Moreover, the Rho kinase
      inhibitor Y27632 had no major effect on the NF-kappaB inhibitory activity of
      pitavastatin. The inhibitory effect of pitavastatin is possibly independent of
      the Rho kinase pathway in inflammation-associated HCC cells is. Finally, the
      addition of TNF-alpha significantly increased IL-6 protein production, which was
      suppressed by the addition of pitavastatin. These results suggest that
      pitavastatin at a low dose (0.1 microM) inhibits NF-kappaB activation and
      decreases IL-6 production induced by TNF-alpha, and is therefore expected to be a
      new strategy for treating HCC.

PMID- 16595894
TI  - Primary structure and organ-specific expression of the rat aryl hydrocarbon
      receptor repressor gene.
AB  - The aryl hydrocarbon receptor repressor (AhRR) is a member of the basic helix
      loop-helix/Per-Arnt-Sim (bHLH/PAS) family of transcription factors, providing a
      negative feedback loop with a xenobiotic or endogenous ligand-dependent signal
      transduction mediated by the AhR. We sequenced full-length AhRR mRNA extracted
      from the heart of a male Wistar rat injected intraperitoneally with 3
      methylcholanthrene (3-MC) 24 h before. The 95.6 kb-long AhRR genome was clarified
      to consist of 11 exons and 10 introns. The constitutive expression of AhRR mRNA
      was prominent in males when compared with females in parallel with the sexual
      difference in AhR expression. Although AhRR was ubiquitously expressed in all
      tissues tested, the levels of AhRR expression were higher in the small intestine,
      where the 3-MC-dependent induction of CYP1A1 transcription was less significant,
      than in the heart, lung, liver, and kidney. The dose-dependent suppression of AhR
      dependent transcriptional activation in both the presence and absence of 3-MC was
      observed in rat liver-derived RL-34 cells transiently transfected with the
      expression plasmid for AhRR in combination with the reporter plasmid.

PMID- 16595895
TI  - Induction of apoptosis by disturbing mitochondrial-membrane potential and
      cleaving PARP in Jurkat T cells through treatment with acetoxyscirpenol
      mycotoxins.
AB  - Paecilomyces tenuipes is a famous Chinese medicinal entomopathogenic fungus that
      grows within the larvae of silkworms. 4beta-acetoxyscirpendiol (4-MAS), a
      cytotoxic compound belonging to the scirpenol subfamily of trichothecene
      mycotoxin, was isolated from Paecilomyces tenuipes. To further elucidate the
      cytotoxic mechanism of 4-MAS, evidences of its induction of apoptosis, together
      with the structurally related acetoxyscirpenol moiety mycotoxins (ASMs) such as,
      15-acetoxyscirpenol (15-MAS), 4,15-diacetoxyscirpenol (4,15-DAS), and 3alpha
      acetyldiacetoxyscirpenol (TAS), in the human Jurkat T cell line were reported
      herein. In the MTT reduction and time-course cytotoxicity assays for monitoring
      cell viability, all the four ASMs that were tested exhibited cytotoxicity; single
      acetoxylation at C-4 of the scirpenol family resulted in relatively weak
      cytotoxicity, while acetoxylation at C-15 resulted in strong cytotoxicity
      regardless of the other acetoxylations at the C-3 and/or C-4 positions.
      Phosphatidylserine externalization was induced by all the ASMs that were treated
      at an early phase in a time-dependent manner, showing a typical apoptotic
      phenomenon, not a necrotic one. The ASMs also reduced the mitochondria's inner
      membrane potential (deltaPsim) through flow cytometry analysis after staining
      these with DiOC6, a mitochondria-specific and voltage-dependent dye.
      Acetoxylation of ASM at C-15 increased deltaPsim disruption, but that at C-3
      reduced the deltaPsim. The ASMs that were tested also cleaved 113 kDa PARP to an
      89-kDa fragment through Western blot assay, suggesting the activation of caspase
      3 and/or caspase-7 in the Jurkat T cell. DNA fragmentation was also observed to
      have been increased in a time-dependent manner by the ASMs that were tested in
      Jurkat T cells, resulting in the DNA fragmentation intensity order of 4,15-DAS>15
      MAS>TAS>4-MAS. These data indicate that the Jurkat T cells that were treated with
      ASMs underwent typical cascades of apoptotic cell death.

PMID- 16595896
TI  - Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant
      melanoma cells.
AB  - Kojic acid is a natural product and normally used as a food additive and
      preservative, a skin-whitening agent in cosmetics, a plant growth regulator and a
      chemical intermediate. Using DNA microarray technology, the overall biological
      effects of kojic acid on the gene expression profiling of a human skin A375
      malignant melanoma cells were examined. After treatment with kojic acid, a total
      of 361 differentially expressed genes were distinctively changed with 136 up
      regulated genes and 225 down-regulated genes. We used the bioinformatics tool to
      search the gene ontology and category classification of differentially expressed
      genes that provided the useful information of expressed genes belonging to
      cellular component, molecular function and biological process in regulation of
      melanogenesis. Seven down-regulated genes of APOBEC1, ARHGEF16, CD22, FGFR3,
      GALNT1, UNC5C and ZNF146 that were typically validated by the real-time
      quantitative PCR (RT-qPCR) analysis technology showed to be the tumor suppressor
      genes in melanoma cancer cells. Thus, microarray technology coupled with RT-qPCR
      offered a high throughput method to explore the number of differentially
      expressed genes responding to kojic acid and their biological functions, and led
      to more understanding of kojic acid effects on skin cancer therapy and related
      side effects. Moreover, the differentially expressed genes may become useful
      markers of skin malignant melanoma for further diagnostic and therapeutic
      applications.

PMID- 16595897
TI  - Induction of apoptosis by Cordyceps militaris through activation of caspase-3 in
      leukemia HL-60 cells.
AB  - Cordyceps militaris is a traditional herbal ingredient frequently used for tonic
      and medicinal purposes in eastern Asia. The hot water extract of its cultivated
      fruiting bodies demonstrated a potent cytotoxic effect against the proliferation
      of the human premyelocytic leukemia cell HL-60, with an IC50 of 0.8 mg/ml for a
      12-h treatment. It induced the characteristic apoptotic symptoms in the HL-60
      cells, including DNA fragmentation and chromatin condensation, occurring within
      12-16 h of treatment at a dose of 1 mg/ml. The activation of caspase-3 and the
      specific proteolytic cleavage of poly (ADP-ribose) polymerase were detected
      during the course of apoptosis induction. These results indicate that the hot
      water extract of Cordyceps militaris fruiting bodies inhibited cancer cell
      proliferation by inducing cell apoptosis through the activation of caspase-3, and
      that the Cordyceps militaris extract may therefore have therapeutic potential
      against human leukemia.

PMID- 16595898
TI  - Effect of oral vitamin E administration on acute gastric mucosal lesion
      progression in rats treated with compound 48/80, a mast cell degranulator.
AB  - The effect of oral vitamin E administration on acute gastric mucosal lesion
      progression was examined in rats treated once with compound 48/80 (C48/80) (0.75
      mg/kg, i.p.) in comparison with that of subcutaneously administered superoxide
      dismutase (SOD) plus catalase (CAT). Vitamin E (50, 100 or 250 mg/kg)
      administered at 0.5 h after C48/80 treatment reduced progressive gastric mucosal
      lesions at 3 h after the treatment dose-dependently, like SOD plus CAT
      administered at the same time point. The gastric mucosa of C48/80-treated rats
      had decreased Se-glutathione peroxidase activity and vitamin E, ascorbic acid,
      and hexosamine contents and increased myeloperoxidase and xanthine oxidase
      activities and thiobarbituric acid reactive substances content at 3 h after the
      treatment. Administered vitamin E attenuated all these changes found at 3 h after
      C48/80 treatment dose-dependently, like administered SOD plus CAT. C48/80-treated
      rats administered with vitamin E (100 or 250 mg/kg) had higher gastric mucosal
      vitamin E content than C48/80-untreated rats. Neither administered vitamin E nor
      SOD plus CAT had any effect on the increases in serum serotonin and histamine
      concentrations and the decrease in gastric mucosal blood flow found at 3 h after
      C48/80 treatment. In the gastric mucosa of C48/80-untreated rats administered
      with vitamin E, thiobarbituric acid reactive substances content decreased with an
      increase in vitamin E content. These results indicate that orally administered
      vitamin E prevents acute gastric mucosal lesion progression in C48/80-treated
      rats possibly by suppressing oxidative stress, neutrophil infiltration, and mucus
      depletion in the gastric mucosa like administered SOD plus CAT.

PMID- 16595899
TI  - Antihypertensive potential and mechanism of action of astaxanthin: III.
      Antioxidant and histopathological effects in spontaneously hypertensive rats.
AB  - We investigated the effects of a dietary astaxanthin (ASX-O) on oxidative
      parameters in spontaneously hypertensive rats (SHR), by determination of the
      level of nitric oxide (NO) end products nitrite/nitrate (NO2-/NO3-) and lipid
      peroxidation in ASX-O-treated SHR. Oral administration of the ASX-O significantly
      reduced the plasma level of NO2-/NO3- compared to the control vehicle (p<0.05).
      The lipid peroxidation level, however, was reduced in both ASX-O- and olive oil
      treated groups. We also analyzed the post-treatment effects of ASX-O on the
      vascular tissues by examining the changes in the aorta and coronary arteries and
      arterioles. The dietary ASX-O showed significant reduction in the elastin bands
      in the rat aorta (p<0.05). It also significantly decreased the [wall : lumen]
      aerial ratio of the coronary arteries. These results suggest that ASX-O can
      modulate the oxidative condition and may improve vascular elastin and arterial
      wall thickness in hypertension.

PMID- 16595900
TI  - Effects of hop extracts on nasal rubbing and sneezing in BALB/c mice.
AB  - The effects of hop extracts (Humulus lupulus L.) on histamine release from rat
      peritoneal mast cells and human basophilic KU812 cells were studied. Hop water
      extract (HWE) and XAD-4 50% methanol fraction of HWE (MFH) inhibited histamine
      release from rat mast cells induced by compound 48/80 at concentrations of 100
      and 10 mug/ml, respectively. Almost the same findings were observed with A23187
      induced histamine release from KU812 cells. Next, we studied the effects of hop
      extracts on antigen-induced nasal rubbing and sneezing in sensitized BALB/c mice.
      HWE caused a significant inhibition of nasal rubbing and sneezing at a dose of
      500 mg/kg. MFH also inhibited nasal rubbing and sneezing dose-dependently. A
      significant difference was observed from 100 mg/kg in nasal rubbing and 200 mg/kg
      in sneezing. The effects of both extracts became clear after repeated
      administration. HWE and MFH significantly inhibited both nasal rubbing and
      sneezing, respectively, after consecutive treatment for 15 d at smaller doses
      compared with single administration. This finding indicates that the active
      component of hop is included in MFH, which was absorbed to Amberlite XAD-4 and
      eluted with 50% methanol. These results clearly demonstrated that hop extracts
      may be effective in the relief of symptoms of allergic rhinitis.

PMID- 16595901
TI  - Immunomodulatory and anti-inflammatory effects of Semecarpus anacardium LINN. Nut
      milk extract in experimental inflammatory conditions.
AB  - Immunomodulatory effects of Semecarpus anacardium LINN. nut milk extract (SA)
      were investigated in adjuvant induced arthritis by studying the alterations in
      humoral and cell mediated immune responses and also the anti-inflammatory effects
      by evaluating the changes in paw edema, tumour necrosis factor (TNF-alpha),
      nitric oxide and myeloperoxidase activities. Pharmacological studies were also
      conducted with SA and indomethacin on experimental animals for evaluating the
      anti-inflammatory, analgesic, antipyretic and ulcerogenic activities. The
      alterations in the humoral and cell mediated immunity were significantly reverted
      back to near normal levels on treatment with SA. The drug significantly reduced
      the elevation in the paw edema, TNF-alpha, nitric oxide and myeloperoxidase
      levels when compared with adjuvant induced arthritic animals, which shows the
      anti-inflammatory activity of the drug. SA showed strong anti-inflammatory
      effects in xylene-induced ear edema and formalin-induced inflammation. In
      analgesic test, the extract elicited a potential activity on both acetic acid
      induced writhing response as well as hot plate test showing its central and
      peripheral mediated action. The drug also elicited antipyretic action in yeast
      induced hyperemia in rats. In addition, the extract did not produce any
      ulceration on gastric mucosa during ulcerogenic test and did not produce any
      serious adverse effects. All these effects are nearly similar to the activities
      of indomethacin except the ulceration where indomethacin produced significant
      ulceration. From this study, the protective immunological and pharmacological
      role of SA is demonstrated.

PMID- 16595902
TI  - Enhancement of veratridine-induced sodium dynamics in NG108-15 cells during
      differentiation.
AB  - Developmental changes in dynamics of Na+ were studied in neuroblastomaxglioma
      hybrid NG108-15 cells during differentiation which was induced by dibutyryl cAMP
      (Bt2cAMP). Ratiometric Na+ imaging with a Na+-sensitive fluorescent dye SBFI
      (sodium-binding benzofuran isophthalate) revealed that the intracellular Na+
      concentration ([Na+]i) was not affected by the application of high K+ (60 mM)
      solution to either control or differentiated cells. When cells were exposed to 50
      microM veratridine (Vtd), an agonist of voltage-sensitive sodium channels
      (VSSCs), a significant increase in [Na+]i was observed in differentiated but not
      in undifferentiated cells. Calculated mean [Na+]i value increased from the basal
      10.4 to 44.1 mM in response to 50 microM Vtd. This Vtd response was reversibly
      inhibited by tetrodotoxin (TTX), a specific blocker for VSSCs, in a dose
      dependent manner (IC50 = 1 nM). It is suggested that VSSCs in NG108-15 cells are
      sensitive to TTX and Vtd and that the number of VSSCs increases during
      differentiation.

PMID- 16595903
TI  - Effect of simultaneous insertion of oleaginous base on the absorption and on the
      anticonvulsant effect of diazepam suppository.
AB  - To clarify the drug-base interaction between diazepam (DZP) suppository and
      oleaginous base, we investigated the effect of simultaneous combination of
      oleaginous base on the absorption and on the anticonvulsant effect of DZP
      Suppository in rats. Simultaneous insertion of DZP suppository and oleaginous
      base significantly decreased maximum concentration (C(max)) and area under the
      blood concentration-time curve (AUC) of plasma DZP concentrations. Administration
      of DZP suppositories (2.5, 5 mg/kg) dose-dependently suppressed the
      pentylenetetrazol (PTZ)-induced seizures, and the anticonvulsant effect of DZP
      suppository (5 mg/kg) was reduced by simultaneous insertion of oleaginous base.
      In an in vitro study using a suppository release apparatus, simultaneous
      combination of DZP suppository and oleaginous base (1.5-98 mg) significantly
      decreased the accumulative release of DZP in a dose-dependent manner. These
      results suggested that when DZP suppository and oleaginous base are inserted
      simultaneously, the released DZP distributes partially to the oleaginous base,
      and this phenomenon is related to the decreases in the plasma concentration and
      the anticonvulsant effect of DZP.

PMID- 16595904
TI  - A derivative of aminopeptidase inhibitor (BE15) has a dual inhibitory effect of
      invasion and motility on tumor and endothelial cells.
AB  - Bestatin is an inhibitor of aminopeptidase N (APN)/CD13 and aminopeptidase B. In
      our previous report, bestatin inhibited the tumor cell invasion and the
      angiogenesis induced by the inoculation of B16-BL6 melanoma cells into mice and
      capillary formation on human umbilical vein endothelial cells (HUVECs) in vitro.
      The results show that the enzymatic activity of APN is deeply involved in tumor
      invasion and angiogenesis. We investigated the effect of three bestatin
      derivatives on A375 human melanoma cells and in vitro. All the derivatives
      inhibited the activity of APN, but BE15 was most effective and controlled the
      migration of A375 cells and HUVECs and capillary formation of HUVECs.
      Furthermore, the bestatin derivatives had an inhibitory effect not only on
      aminopeptidase activity but also on cell motility. Compared with bestatin and the
      other derivatives, BE15 had a marked inhibitory effect on the formation of
      capillary structure by HUVECs in vitro. These results suggest that new anti
      metastatic and anti-angiogenic agents, which have a dual inhibitory effect on the
      degradation of the extra cellular matrix and cell motility, may be developed from
      bestatin.

PMID- 16595906
TI  - Different pathways for activation of extracellular signal-regulated kinase
      through thromboxane A2 receptor isoforms.
AB  - Thromboxane A2 receptor (TP) consists of two alternatively spliced isoforms,
      TPalpha and TPbeta, which differ in their cytoplasmic tails. In the present
      study, we examined the difference in signal transduction of TPalpha and TPbeta,
      using stably expressing cells of TPalpha and TPbeta. The cells expressing TPalpha
      (TPalpha-SC2) and TPbeta (TPbeta-SC15) were selected based on the similar binding
      sites of [3H]-SQ29548, a TP antagonist. U46619, a TP agonist, elicited
      phosphoinositide hydrolysis in TPalpha-SC2 and TPbeta-SC15 cells with a similar
      concentration-dependency. U46619 also caused the phosphorylation of extracellular
      signal-regulated kinase (ERK1/2) in both TPalpha-SC2 and TPbeta-SC15 cells. While
      the peak of the phosphorylation of ERK1/2 was observed 5 min after addition of
      U46619 in TPalpha-SC2 cells, the long lasting phosphorylation up to 60 min was in
      TPbeta-SC15 cells. U46619-induced phosphorylation of ERK1/2 at 5 min was
      inhibited by pertussis toxin in both cells, suggesting that G(i) is involved in
      the phosphorylation mediated via both TP isoforms. Interfering G(12/13) activity
      by overexpression of p115-RGS reduced U46619-induced ERK1/2 phosphorylation in
      TPbeta-SC15 cells, but not in TPalpha-SC2 cells. H89, an inhibitor of protein
      kinase A (PKA), reduced U46619-induced ERK1/2 phosphorylation in TPalpha-SC2
      cells, but not in TPbeta-SC15 cells. These results indicate that G(i) may be
      involved in TP-mediated ERK1/2 phosphorylation in both isoforms. In addition, H89
      sensitive kinase and G(12/13) may be involved in TP-mediated ERK1/2
      phosphorylation in TPalpha and TPbeta, respectively.

PMID- 16595905
TI  - Edaravone inhibits JNK-c-Jun pathway and restores anti-oxidative defense after
      ischemia-reperfusion injury in aged rats.
AB  - Edaravone, a potent antioxidant, is currently being used in the management of
      acute ischemic stroke in relatively high-aged populations. Mitogen activated
      protein kinase (MAPK) pathways have been shown to play important roles in
      neuronal cell death. We examined the role of MAPK pathways and the effect of
      treatment with edaravone in the brain after cerebral ischemia-reperfusion (I/R)
      injury in a bilateral carotid artery occlusion (BCAO) model with ischemia for 85
      min followed by reperfusion for 45 min in aged rats. Western immunoblotting,
      immunostaining, enzyme-linked immunosorbent assay (ELISA), spectrophotometry,
      terminal deoxynucleotidyl transferase nick end labeling (TUNEL) and triphenyl
      tetrazolium chloride (TTC) staining were performed to evaluate various proteins
      in the homogenate, c-Jun NH2-terminal kinase (JNK) in the tissue sections,
      protein carbonyl, glutathione peroxidase (GSHPx), apoptosis and infarct size,
      respectively. Our results showed that I/R injury resulted in a reduction of
      GSHPx, but protein carbonyl content and inducible nitric oxide synthase were
      increased. The activation of JNK and its downstream molecule c-Jun was
      significantly increased after injury, whereas the activities of p38 MAPK and
      extracellular-regulated kinase 1/2 were slightly but not significantly increased.
      Edaravone (3 mg/kg, i.v.) treatment significantly reduced all of these changes.
      Our findings suggest that the JNK pathway differentially mediates neuronal injury
      in aged rats after BCAO, and edaravone treatment significantly reduces the
      neuronal damage after I/R injury by inhibiting oxidative stress and the JNK-c-Jun
      pathway with concomitant inhibition of overall MAPK activity in the brains of
      aged rats.

PMID- 16595907
TI  - Antioxidant activity of four endemic Stachys taxa.
AB  - Methanol extracts of aerial flowering parts of four endemic Stachys taxa: S.
      anisochila VIS. et PANCIC, S. beckeana DORFLER & HAYEK, S. plumosa GRISEB. and S.
      alpina L. ssp. dinarica MURB. were investigated on their antioxidant activity.
      The extracts were studied for total antioxidant activity (TAA), along with 1,1
      diphenyl 2-picryl hydrazyl (DPPH) and OH radical scavenging activity, and lipid
      peroxidation (LP). High correlations between total phenolics content, TAA and
      scavenging DPPH radical indicate that polyphenols are the main antioxidants. All
      Stachys extracts, with the exception of S. plumosa, exhibited high anti-DPPH
      activity (IC50<50 microg/ml). In concentration range from 6.25 to 50 microg/ml,
      all extracts scavenged OH radical above 40%, with maximal inhibitions for S.
      anisochila, S. alpina ssp. dinarica and S. beckeana extracts of 50.22%, 50.94%
      and 64.97%, respectively. Only S. plumosa extract achieved maximal activity of
      60.67% at 100 microg/ml. As for LP, IC50 values for S. beckeana and S. alpina
      ssp. dinarica extracts were 25.07 and 49.00 microg/ml, respectively, while S.
      anisochila and S. plumosa extracts did not reach 50% of LP inhibition.

PMID- 16595908
TI  - Combined effects of benidipine and diltiazem on cardiohemodynamics in
      anesthetized dogs.
AB  - We examined the combined effects of the calcium channel blockers 1,4
      dihydropyridine (benidipine) and benzothiazepine (diltiazem) on
      cardiohemodynamics in anesthetized dogs. Benidipine (3 microg/kg) lowered blood
      pressure (BP) slightly and continuously increased coronary flow (CF). Diltiazem
      (300, 1000 microg/kg) decreased BP, heart rate (HR), and the maximum rate of rise
      of left ventricular pressure (LV dP/dt max) with the increase of doses. Diltiazem
      increased CF, though it was transient when compared to benidipine. A combination
      of benidipine (3 microg/kg) and diltiazem (300 microg/kg) showed continuous
      decreases in BP, HR, and LV dP/dt max, and an increase in CF that was similar to
      that recorded for the benidipine group. The level of double product (DP: systolic
      BPxHR, an index of myocardium energy consumption) in the combination group was
      significantly lower than that of the benidipine group. The plasma concentrations
      of benidipine and diltiazem in the combination group were similar to those of the
      groups receiving either drug. These results demonstrate that the combination of
      benidipine and diltiazem increases CF more continuously than diltiazem alone, and
      decreases DP more potently than benidipine alone, indicating that the combination
      therapy possesses favorable properties as a treatment for angina pectoris.
      Therefore, the combination of benidipine and diltiazem is suggested as a useful
      treatment for improving the clinical benefits of monotherapy for angina, compared
      with the use of diltiazem alone at higher doses.

PMID- 16595909
TI  - Antioxidant effects of quinoline alkaloids and 2,4-di-tert-butylphenol isolated
      from Scolopendra subspinipes.
AB  - The oxidized low-density lipoprotein (ox-LDL) plays a critical role at the early
      stages of atherosclerosis. Thus, the prevention of LDL-oxidation by antioxidants
      may arrest the progression of atherosclerosis. Two quinoline alkaloids, 3,8
      dihydroxyquinoline (1) and 2,8-dihydroxy-3,4-dimethoxyquinoline (3), and 2,4-di
      tert-butylphenol (2) were isolated from the dried body of Scolopendra
      subspinipes. Compounds 1-3 exhibited antioxidant activities on copper-mediated
      (1: IC50=2.6 microM, 2: IC50=8.2 microM, 3: IC50=63.0 microM), AAPH-mediated
      oxidation (1: IC50=3.9 microM, 2: IC50=9.9 microM, 3: IC50=71.8 microM), and SIN
      1-mediated oxidation (1: 70%, 2: 52%, 3: 29% at 5.0 microM) in the TBARS assay.
      The antioxidant activities of compounds 1-3 were tested with respect to other
      parameters, such as the lag time of conjugated diene fromation, relative
      electrophoretic mobility (REM) of ox-LDL, and apoB-100 fragmentation on copper
      mediated LDL-oxidation. In addition, compounds 1-3 showed 1,1-diphenyl-2
      picrylhydrasyl (DPPH) radical scavenging activity and compound 1 also exhibited
      metal chelating activity.

PMID- 16595910
TI  - Phenolic constituents of Malus doumeri var. formosana in the field of skin care.
AB  - Plant phenolic compounds isolated from a 70% aqueous acetone extract of the
      leaves of Malus doumeri A. CHEV. var. formosana (KAWAK. & KOIDZ.) S. S. YING, a
      type of Taiwanese indigenous plant, were evaluated for potential application in
      the field of skin care. A phytochemical investigation of the active fractions
      resulted in the isolation of seven compounds of which the structures were
      identified by spectroscopic characterization. In the present study, the isolated
      phenolic compounds were evaluated for their free radical-scavenging activities
      against 1,1-diphenyl-2-picrylhydrazyl (DPPH) and the superoxide radicals, anti
      elastase, and for their anti-matrix metalloproteinase-1 (MMP-1) activity in human
      skin fibroblast cells. Of these compounds, 3-hydroxyphloridzin (2), 3
      hydroxyphloretin (6), and quercetin (7) exhibited the strongest DPPH and
      superoxide radical-scavenging activities. The IC50 values of these compounds were
      9.2, 7.7, and 15.4 microM, respectively, for the DPPH radical, and 25.0, 19.6,
      and 42.6 microM, respectively, for the superoxide radical. 3-Hydroxyphloridzin
      (2) and 3-hydroxyphloretin (6) also showed xanthine oxidase inhibitory activity,
      with IC(50) values of 52.1 and 22.4 muM, respectively. In the test for elastase
      inhibitory activity, phloretin (5) and 3-hydroxyphloretin (6) were the most
      potent compounds. Phloretin (5), 3-hydroxyphloretin (6), and quercetin (7) showed
      better inhibition of MMP-1 production in fibroblast cells. To the best of our
      knowledge, this is the first time that the active phenolic compounds from M.
      doumeri var. formosana have been isolated, reported, and described. The above
      results suggest that the extract of M. doumeri var. formosana containing phenolic
      compounds could be suitable naturally occurring active constituents for use in
      anti-aging or cosmetic products.

PMID- 16595911
TI  - Studies on cultivated ephedra plants in inner mongolia autonomous region and
      ningxia hui autonomous region.
AB  - Progression of the desertification in northern China has been causing damage to
      wild Ephedra plants on which we depend for most of supply of the traditional
      herbal medicine, "Ma huang." The Chinese government encourages the cultivation of
      Ephedra plants, and Ephedra fields have been reclaimed in the original Ephedra
      habitats in recent years. We surveyed 7 Ephedra fields that have been recently
      developed in the Inner Mongolia Autonomous Region and Ningxia Hui Autonomous
      Region to collect information on Ephedra plant cultivation, especially pertaining
      to crop species. Specimens taken from those Ephedra fields were genetically and
      morphologically analyzed, and their ephedrine alkaloid content was examined. DNA
      analyses of Ephedra specimens, including DNA sequencing of ITS (internal
      transcribing sequence of nuclear ribosomal DNA) and trn L/F (intron of trnL and
      intergenic spacer between the trnL and trnF of chloroplast DNA) region and
      species-specific amplification of trn L/F were conducted to identify Ephedra
      species. Based on the results of DNA sequencing and morphological determination,
      the crops grown in 6 fields ware identified as Ephedra sinica, while co-planting
      of E. sinica and E. intermedia was found in one field where a higher appearance
      rate of plants with varied morphology from wild Ephedra plants was observed.
      Furthermore, direct sequencing of the PCR product of the trn L/F region of some
      specimens from the field and their species-specific PCR showed ambivalent result.
      Cloning and sequencing of the PCR product of the trn L/F region of those
      specimens DNA suggested their heteroplasmy, containing both E. sinica- and E.
      intermedia-type chloroplasts. On the other hand, the profile of the ephedrine
      alkaloid content was clearly correlated with the result of direct sequencing of
      the trn L/F region; the specimens showing the E. sinica-type sequence contained
      more ephedrine than pseudoephedrine, and the specimens of the E. intermedia-type
      more pseudoephedrine.

PMID- 16595912
TI  - Increase in the free radical scavenging activity of ginseng by heat-processing.
AB  - To investigate whether or not the radical scavenging activity of ginseng is
      enhanced by heat processing, we evaluated the scavenging effects of white ginseng
      (WG), red ginseng (RG, steamed ginseng at 98-100 degrees C) and sun ginseng (SG,
      steamed ginseng at 120 degrees C) on nitric oxide, superoxide (O2-), hydroxyl
      (*OH) radicals and peroxynitrite (ONOO-). Heat-treated ginseng (RG and SG) showed
      better O2-, ONOO- and *OH-scavenging activities than WG. In particular, the
      radical scavenging activities of SG were stronger than those of RG. Furthermore,
      we evaluated the radical scavenging activities of maltol, salicylic acid,
      vanillic acid and p-coumaric acid, known as principal antioxidant components of
      ginseng, in WG, RG and SG, and also investigated their contents. Of the tested
      compounds, maltol, vanillic acid and p-coumaric acid exhibited ONOO(-)-scavenging
      activity. In addition, maltol and p-coumaric acid showed strong *OH-scavenging
      activity. Moreover, the content of maltol was remarkably increased in a
      temperature-dependent manner by heat processing, implying that maltol was closely
      related to the radical scavenging activity of heat-processed ginseng. These
      findings indicate that SG may act as a free radical scavenger and protect against
      damage caused by oxidative stress related with these radicals.

PMID- 16595913
TI  - 5alpha,8alpha-Epidioxy-22E-ergosta-6,9(11),22-trien-3beta-ol from an edible
      mushroom suppresses growth of HL60 leukemia and HT29 colon adenocarcinoma cells.
AB  - We purified a sterol with antitumor activity from the edible mushroom Sarcodon
      aspratus (BERK.) S. ITO and identified it as 5alpha,8alpha-epidioxy-22E-ergosta
      6,9(11),22-trien-3beta-ol (9,11-dehydroergosterol peroxide (9(11)-DHEP)).
      Purified 9(11)-DHEP was a more effective inhibitor of HL60 leukemia cell growth
      and stronger apoptosis-inducer than 5alpha,8alpha-epidioxy-22E-ergosta-6,22-dien
      3beta-ol (ergosterol peroxide (EP)) that we had previously identified as an
      apoptosis inducer. Moreover, 9(11)-DHEP selectively suppressed the growth of HT29
      human colon adenocarcinoma cells but not WI38 normal human fibroblasts. After 5 d
      incubation of HT29 with 7 microM 9(11)-DHEP, the number of S phase cells
      decreased from 23 to 15% of total diploid cells and 17% became hypodiploid.
      Expression of the cyclin-dependent kinase inhibitor 1A (p21, WAF1, Cip1)
      (CDKN1A), which has been shown to cause cell cycle arrest and apoptosis in HT29
      cells, was induced by 9(11)-DHEP. These results suggest that 9(11)-DHEP inhibits
      HT29 cell growth by inducing CDKN1A expression, thus causing cell cycle arrest
      and apoptosis.

PMID- 16595914
TI  - The protective role of Chinese prescription Kangen-karyu extract on diet-induced
      hypercholesterolemia in rats.
AB  - This study was carried out to investigate the protective potential of Chinese
      prescription Kangen-karyu, comprising six crude drugs, on coronary heart disease
      which is the principal cause of morbidity and mortality worldwide. The diet
      induced hypercholesterolemic rat model, which shows an elevation in low density
      lipoprotein (LDL) cholesterol and atherosclerosis, was employed. The control rats
      fed a diet of 1% cholesterol and 0.5% cholic acid showed the highest cholesterol
      levels in serum and feces relative to those fed a normal diet, however, the rats
      administered Kangen-karyu extract showed reductions in these levels without
      changes in liver cholesterol, indicating that the reduction of serum total
      cholesterol by Kangen-karyu extract probably arises from an increase in
      cholesterol excretion. Furthermore, the administration of Kangen-karyu extract
      significantly prevented the elevation of serum aspartate aminotransferase and
      alanine aminotransferase, known as marker enzymes of liver damage. The elevated
      serum levels of LDL cholesterol were lowered, however, the high density
      lipoprotein cholesterol level was significantly elevated by Kangen-karyu extract
      and these were dose-dependent decreases in the atherogenic index to 15.2, 8.8 and
      7.5 at oral doses of 50, 100 and 200 mg from the 19.4 control value,
      respectively. In addition, Kangen-karyu extract inhibited LDL oxidation in a dose
      dependent manner, and the elevated level of thiobarbituric acid-reactive
      substances in control rats showed a decline by the administration of Kangen-karyu
      extract. The present study suggests that Kangen-karyu could play a protective
      role against hypercholesterolemia through the regulation of cholesterol levels
      and inhibition of lipid peroxidation.

PMID- 16595915
TI  - Characterization of the radical-scavenging reaction of 2-O-substituted ascorbic
      acid derivatives, AA-2G, AA-2P, and AA-2S: a kinetic and stoichiometric study.
AB  - The aim of this study was to characterize the antioxidant activity of three
      ascorbic acid (AA) derivatives O-substituted at the C-2 position of AA: ascorbic
      acid 2-glucoside (AA-2G), ascorbic acid 2-phosphate (AA-2P), and ascorbic acid 2
      sulfate (AA-2S). The radical-scavenging activities of these AA derivatives and
      some common low molecular-weight antioxidants such as uric acid or glutathione
      against 1,1-diphenyl-picrylhydrazyl (DPPH) radical, 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS+), or galvinoxyl
      radical were kinetically and stoichiometrically evaluated under pH-controlled
      conditions. Those AA derivatives slowly and continuously reacted with DPPH
      radical and ABTS+, but not with galvinoxyl radical. They effectively reacted with
      DPPH radical under acidic conditions and with ABTS+ under neutral conditions. In
      contrast, AA immediately quenched all species of radicals tested at all pH values
      investigated. The reactivity of Trolox, a water-soluble vitamin E analogue, was
      comparable to that of AA in terms of kinetics and stoichiometrics. Uric acid and
      glutathione exhibited long-lasting radical-scavenging activity against these
      radicals under certain pH conditions. The radical-scavenging profiles of AA
      derivatives were closer to those of uric acid and glutathione rather than to that
      of AA. The number of radicals scavenged by one molecule of AA derivatives, uric
      acid, or glutathione was equal to or greater than that by AA or Trolox under the
      appropriate conditions. These data suggest the potential usage of AA derivatives
      as radical scavengers.

PMID- 16595916
TI  - Multiple regression analysis of pharmacogenetic variability of carvedilol
      disposition in 54 healthy Japanese volunteers.
AB  - The aim of this study was to evaluate the pharmacogenetic variability in the
      disposition of carvedilol in the Japanese population. Five or 10 mg of carvedilol
      was orally administered to 54 healthy Japanese subjects (22-44 years old), and
      blood samples were taken at 2 and 6 h after dosing. We determined the polymorphic
      alleles of CYP2D6, CYP2C9, CYP2C19, CYP3A5, UGT2B7, and MDR1 in each subject. The
      whole blood concentration of R- and S-carvedilol was measured by an HPLC method.
      The pharmacokinetic parameters in individual subjects were estimated by the
      Bayesian method using the nonlinear mixed effects model (NONMEM) program. We then
      examined the effect of the genetic polymorphisms on the variability in the
      pharmacokinetics of carvedilol using a multiple regression analysis. The oral
      clearance (CL/F) and also apparent volume of distribution (V/F) of both
      enantiomers were significantly lower in the subjects with the CYP2D6*10 allele
      than those with the CYP2D6*1/*1, *1/*2, or *2/*2 genotype, confirming our
      previous finding that the bioavailability (F) and systemic clearance (CL) of R-
      and S-carvedilol in the liver is significantly altered in Japanese with the
      CYP2D6*10 allele. On the other hand, CYP2C9*3, CYP2C19*2, CYP2C19*3, CYP3A5*3,
      UGT2B7*2, and MDR1 C3435T did not significantly affect the pharmacokinetics of
      carvedilol in Japanese subjects.

PMID- 16595917
TI  - Relationship between excretion clearance of rhodamine 123 and P-glycoprotein
      (Pgp) expression induced by representative Pgp inducers.
AB  - P-Glycoprotein (Pgp) locates in several tissues in the living body and acts as an
      efflux pump for many drugs. In this study, the usefulness of intravenous
      rhodamine 123 (Rho123) administration as a marker for detecting the inducing
      effect of Pgp by drugs was identified, and the relationship between excretion
      clearances of Rho123 via Pgp and its expression during treatment with the
      representative Pgp inducers rifampicin (RFP), dexamethasone (DEX) and St. John's
      Wort (SJW) were examined in rat liver, intestine and kidney. After pretreatment
      with RFP (10 mg/kg/d) for 4 d, DEX (50 mg/kg/d) for 4 d or SJW (15 mg/kg/d) for 7
      d orally, the biliary excretion of Rho123 after intravenous administration (0.2
      mg/kg) increased significantly by 40%, 55% and 14%, respectively, and the
      intestinal excretion increased significantly by 24%, 50% and 27%, respectively,
      as compared with the controls. In contrast, there were no notable changes in the
      urinary excretion of Rho123 among rats that received these inducers. Western blot
      analysis with a monoclonal antibody for Pgp (C219) showed that Pgp levels in the
      small intestine and liver in the inducer-treated rats increased markedly as
      compared with the controls. In addition, there was a significant correlation
      between the induction levels of Pgp in the liver or small intestine and their
      clearance ratios (r2=0.7583, p<0.05), but not in the kidney. These observations
      suggest that the excretion clearances of Rho123 from blood circulation to the
      small intestine or to the bile after its intravenous administration are useful
      indicators to assess the Pgp function in the presence of Pgp inducers.

PMID- 16595918
TI  - Carrier-mediated transport of glycerol in the perfused rat small intestine.
AB  - Studies using the closed loop and everted sacs of the rat small intestine
      recently prompted us to suggest that carrier-mediated transport is involved in
      the intestinal absorption of glycerol. Although it could be mediated by a novel
      carrier system, little information is available. The aim of the present study was
      to kinetically characterize carrier-mediated glycerol transport in the perfused
      rat small intestine to help in identifying the carrier involved and to explore
      the possibility that the carrier might be used as a pathway for oral drug
      delivery and a target for drug development. In situ single-pass perfusion was
      conducted using a 10-cm midgut segment of the male Wistar rat, and the absorption
      of [3H]glycerol was evaluated by its disappearance from the intestinal lumen. The
      absorption of glycerol was saturable and significantly reduced by removing Na+
      from the perfusion solution, suggesting the involvement of a Na+-dependent
      carrier-mediated transport system. The concentration-dependent absorption profile
      was successfully analyzed by assuming Michaelis-Menten type carrier-mediated
      transport and simultaneous passive (diffusive) transport. The maximum transport
      rate (J(max)) was 77.0 pmol/s/cm2 and the Michaelis constant (K(m)) was 1.04 mM,
      giving a J(max)/K(m) of 7.39 x 10(-5) cm/s. The membrane permeability coefficient
      for passive transport (P(m,d)) was 6.89 x 10(-5) cm/s, slightly smaller than
      J(max)/K(m). Therefore, it could be the major mechanism of intestinal glycerol
      absorption in the low concentration range where carrier-mediated transport
      conforms to linear kinetics represented by J(max)/K(m). Furthermore, carrier
      mediated glycerol transport was found to be inhibited by glycerol 3-phosphate,
      monoacetin and diglycerol, indicating that the carrier system may be shared by
      these structural analogues. Thus, the present study has successfully demonstrated
      and characterized carrier-mediated glycerol transport in the perfused rat small
      intestine which is a physiologically relevant model.

PMID- 16595920
TI  - Soluble guanylyl cyclase inhibitor prevents Sema3F-induced collapse of axonal and
      dendritic growth cones of dentate granule cells.
AB  - Controlling axon and dendrite elongation is critical in developing precise neural
      circuits. Using isolated cultures of dentate granule neurons, we succeeded in
      simultaneously monitoring the behaviors of axonal and dendritic outgrowth. Our
      previous study shows that cAMP contributes differentially to Sema3F-induced
      responses of axons and dendrites, but we report here that the cGMP modulation
      does not have such a striking axo-dendritic difference. Treatment with Sema3F
      induced collapse of about 90% growth cones, and pretreatment with 1 muM LY83583,
      an inhibitor of soluble guanylyl cyclase, partially alleviated the collapse of
      both axons and dendrites. Thus, unlike cAMP, cGMP modulates axonal and dendritic
      extension in a similar manner.

PMID- 16595919
TI  - Inhibitory effects of magnolol on distal colon of guinea pig in vitro.
AB  - The influence of plant product magnolol (0-100 microM) on the contractile
      activity of isolated colonic muscle strips in guinea pig and related mechanism
      were investigated. Magnolol did not affect the base tone of colon muscle strips,
      but it dose-dependently inhibited 40 mM KCl-, 1 microM carbachol (CCh)- and 10
      microM serotonin (5-HT)-induced contractions at concentrations higher than 10
      microM. And also, magnolol inhibited the 5-HT- or CCh-induced muscle contraction
      in calcium-free buffer. Furthermore, magnolol inhibited the KCl-induced
      contraction under the condition of procaine. In addition, inhibition rate of
      nifedipine plus magnolol on muscle strips was lower than that of nifedipine
      alone. Moreover, magnolol dose-dependently decreased the velocity of pellet
      propulsion in the concentration range of 0.1-10 microM, and totally inhibited
      pellet propulsion at the concentration higher than 30 microM. Thus, it can be
      concluded that magnolol may 1) block receptor-operated cation channels and the
      voltage dependent Ca2+ channel, and 2) inhibit calcium release from the
      sarcolemmal membrane (SR) through blocking InsP3-sensitive and ryanodine
      sensitive pathways. This explains, at least partially, that Cortex magnoliae
      officinalis exerts therapeutic effects on gastrointestinal disease through
      relaxation of GI tract smooth muscles.

PMID- 16595921
TI  - The inhibitory effect of disodium cromoglycate on the growth of Chlamydophila
      (Chlamydia) pneumoniae in vitro.
AB  - Chlamydophila (Chlamydia) pneumoniae is associated with asthma and several other
      respiratory illnesses. Disodium cromoglycate (DSCG) is known to inhibit both
      immediate and late asthmatic responses. In this study, the inhibitory effect of
      DSCG on the growth of C. pneumoniae was examined by minimum inhibitory
      concentration (MIC) and pre-inoculation minimal cidal concentration (MCC) assays
      using HL cells and C. pneumoniae AR-39. DSCG below the clinically relevant
      concentration inhibited the growth of C. pneumoniae in a dose-dependent manner in
      both the MCC and MIC assays. The inhibitory effect was also time-dependent in the
      MCC assay at 20 mg/ml of DSCG. These results warrant further clinical study on
      the connection between C. pneumoniae infections and use of DSCG.

PMID- 16595922
TI  - Functional gene cloning and characterization of MdeA, a multidrug efflux pump
      from Staphylococcus aureus.
AB  - A DNA fragment conferring drug resistance was cloned from the chromosomal DNA of
      Staphylococcus aureus N315 using a drug hypersensitive Escherichia coli KAM32 as
      the host. Although E. coli KAM32 cells were sensitive to many antimicrobial
      agents, transformed cells harboring a recombinant plasmid carrying the DNA region
      became resistant to several structurally unrelated antimicrobial agents, such as
      tetraphenylphosphonium chloride, Hoechst 33342 and norfloxacin. These results
      suggest that the cloned DNA fragment carries a gene(s) encoding a multidrug
      efflux pump. We partially determined the nucleotide sequence of the cloned DNA
      and found the mdeA gene within it. The E. coli cells transformed with the mdeA
      gene showed efflux activity of Hoechst 33342. On the other hand, S. aureus cells
      transformed with mdeA showed elevated resistance to doxorubicin, daunorubicin,
      tetraphenylphosphonium chloride, Hoechst 33342, ethidium bromide and rhodamine
      6G. Elevated energy-dependent efflux of ethidium was observed with transformed S.
      aureus. We found that the mdeA gene was expressed under normal growth conditions
      in S. aureus N315.

PMID- 16595923
TI  - Effects of amelioration of total flavonoids from stems and leaves of Scutellaria
      baicalensis Georgi on cognitive deficits, neuronal damage and free radicals
      disorder induced by cerebral ischemia in rats.
AB  - Previous studies reported that the total flavonoids from the stems and leaves of
      Scutellaria baicalensis Georgi (TFSS) could enhance and improve learning and
      memory abilities in experimental animals, and reduce the neuronal pathologic
      alterations induced by some reagents in mice. The present study examined whether
      TFSS can improve memory dysfunction, neuronal damage, and abnormal free radicals
      induced by permanent cerebral ischemia in rats. The permanent cerebral ischemic
      model in rats was produced by bilateral ligation of the common carotid arteries.
      The influence of permanent cerebral ischemia on learning and memory was
      determined in the Morris water maze. The neuronal damage in the hippocampus and
      cerebral cortex was assessed by the neuronal morphologic observations. The
      contents of malondialdehyde (MDA) and nitric oxide (NO), and the activities of
      superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and cerebral
      cortex were measured using thiobarbituric acid, nitrate reductase, xanthine
      xanthine oxidase, and ammonium molybdate spectrophotometric methods,
      respectively. In learning and memory performance tests, cerebral ischemic rats
      always required a longer latency time to find the hidden platform and spent a
      shorter time in the target quadrant in the Morris water maze. TFSS 17.5-70 mg.kg(
      1) daily orally administered to ischemic rats for 20 d, from day 16-35 after
      operation differently reduced the prolonged latency and increased swimming time
      spent in the target quadrant. In neuronal morphologic observations, daily oral
      TFSS 17.5-70 mg.kg(-1) for 21 d, from day 16-36 after operation markedly
      inhibited the ischemia-induced neuronal damage. In addition, the increased
      contents of MDA and NO, and SOD activity, and the decreased activity of CAT in
      the hippocampus and cerebral cortex induced by cerebral ischemia were differently
      reversed. The reference drug piracetam (140 mg.kg(-1) per day for 20-21 d)
      similarly improved impaired memory and neuronal damage but had no significant
      effects on free radicals in ligated rats. TFSS can improve memory deficits and
      neuronal damage in rats after permanent cerebral ischemia, which may be
      beneficial in the treatment of cerebrovascular dementia.

PMID- 16595924
TI  - Evaluation of the central activity of hydroxydihydrocarvone.
AB  - The central effects of hydroxydihydrocarvone (HC), an analogue of several
      monoterpenes, were evaluated in animal models. General behavior, locomotor
      activity, pentobarbital-induced sleeping time, pentylenetetrazol (PTZ)-induced
      convulsions, and acetic acid-induced writhing were evaluated in mice. The
      compound caused palpebral ptosis, decreased the response to touch, and increased
      sedation (general behavioral profile). HC (50-200 mg/kg) caused a significant
      dose-dependent decrease in the spontaneous motor activity of mice. This compound
      (100, 200 mg/kg) potentiated the pentobarbital sleeping time, indicating a
      depressant action. HC also protected the mice against PTZ-induced convulsions at
      400 mg/kg. In the acetic acid-induced writhing, the antinociceptive activity of
      HC was demonstrated with a significant dose-dependent response at a dose range of
      25-400 mg/kg. The present results provide evidence that HC has significant
      psychopharmacologic activity with depressant effects.

PMID- 16595925
TI  - The effects of BR003 on memory and cell proliferation in the dentate gyrus of rat
      hippocampus.
AB  - BR003 is a multi-herbal formula that contains twelve medicinal herbs. We
      investigated the effects of oral administration of BR003 to Wistar rats on (a)
      learning and memory using a passive avoidance test and (b) cell proliferation in
      the dentate gyrus (DG) of the hippocampus using immunohistochemical analysis of 5
      bromo-2-deoxyuridine (BrdU) expression. In the passive avoidance test, the
      retention time of the BR003-treated group was significantly longer than that of
      the control group (182.64+/-39.88 vs. 73.08+/-29.30 s, respectively; n=11;
      p<0.05). There were significantly more BrdU-immunoreactive cells in the DG in the
      BR003-treated group than in the control group (1281.07+/-151.16 vs. 818.01+/
      132.98 cells per DG, respectively; n=11; p<0.05). These results suggest that the
      administration of BR003 not only improves learning and memory but also increases
      cell proliferation in the DG of the rat hippocampus.

PMID- 16595926
TI  - Selective cytotoxic activity of valinomycin against HT-29 Human colon carcinoma
      cells via down-regulation of GRP78.
AB  - Glucose deprivation is a fundamental feature of poorly vascularized solid tumors
      and leads to activation of the molecular chaperone GRP78, which is associated
      with the unfolded protein response (UPR), a stress-signaling pathway, in tumor
      cells. We recently isolated an active compound, M126, that inhibits transcription
      from a GRP78 promoter reporter construct. M126 was identified as valinomycin by
      various spectroscopic methods. We found that valinomycin prevents UPR-induced
      protein expression, such as GRP78 and GRP94. The GRPs-inhibitory action of
      valinomycin severe hypoglycemic and results in selective cell death of the
      stressed cancer cells. Our findings demonstrate that GRP78 may be an excellent
      target for the use of cancer chemotherapy in the treatment of solid tumors.

PMID- 16595927
TI  - In vivo measurement of presynaptic Zn2+ release during forebrain ischemia in
      rats.
AB  - Previous studies have suggested that during forebrain ischemia, considerable Zn2+
      is released from synaptic vesicles of gultamatergic neuronal terminals and
      accumulates in hippocampal CA1 pyramidal neurons, leading to delayed neuronal
      death. However, since a time lag exists between the accumulation of Zn2+ and the
      occurrence of ischemia and there are conflicting reports about the amount of Zn2+
      released, the level of released Zn2+ during ischemia in vivo is still unclear. In
      this study, we investigated the temporal change of extracellular Zn2+ in the
      hippocampal CA1 area using microdialysis and the accumulation of Zn2+ in
      hippocampal CA1 neurons with TSQ staining in rats with a transient forebrain
      ischemia. The level of extracellular Zn2+ in the CA1 area increased transiently
      reaching a peak 15 min after occlusion, then decreased with time, returning to
      the basal level 15 min after reperfusion. In addition, at this peak, the level of
      extracellular Zn2+ was about twice the basal level. Assessment of the
      intracellular Zn2+ in hippocampal neurons with TSQ revealed that Zn2+ accumulate
      at 24 h, but not 0 and 6 h after ischemia. These results suggest that, although
      the synaptic vesicular Zn2+ is released into the synaptic cleft during ischemia
      in vivo, the amount of released Zn2+ might not be so excessive, and it does not
      accumulate in hippocampal CA1 pyramidal neurons immediately after ischemia.

PMID- 16595928
TI  - Influence of hypothyroidism induced by thiamazole on the toxicity of
      amitriptyline in chick embryos.
AB  - The effect of hypothyroidism induced by thiamazole on the toxicity of
      amitriptyline was studied in chick embryos. Fertilized eggs of White Leghorns
      were incubated and investigated. 1.2 mg/0.2 ml/egg of thiamazole was injected
      into the albumen of fertilized eggs on the 9th day of incubation. The control
      group was given 0.2 ml/egg of physiological saline in the same manner.
      Amitriptyline at 1 mg/egg was injected into the air sac of fertilized eggs on the
      16th day of incubation. Electrocardiograms were recorded 0 to 60 min after the
      injection. After the injection of amitriptyline into the thiamazole-treated eggs,
      the heart rate was significantly decreased compared with the untreated eggs.
      These findings indicate that hypothyroidism induced by thiamazole has a marked
      influence on the toxicity of amitriptyline in chick embryos.

PMID- 16595929
TI  - Characterization of the halothane-anesthetized guinea-pig heart as a model to
      detect the K+ channel blocker-induced QT-interval prolongation.
AB  - Our previous study using the urethane-anesthetized guinea-pig model has shown
      that an I(Ks) blocker chromanol 293B hardly affects the QT interval itself nor
      potentiates the I(Kr) blocker-induced QT-interval prolongation. The former is in
      good accordance with the previous results in the human isolated intact
      ventricular tissue, but the latter is in sharp contrast with them. In this study,
      we characterized the ventricular repolarization ability of a newly developed
      halothane-anesthetized guinea-pig model by using I(Kr) and I(Ks) blockers.
      Intravenous administration of a selective I(Kr) blocker d-sotalol (3 mg/kg)
      prolonged the QT interval by +27 ms. On the other hand, intravenous
      administration of chromanol 293B (1 mg/kg) prolonged the QT interval by +35 ms,
      and additional administration of the same dose of d-sotalol further prolonged the
      QT interval by +48 ms. These results suggest that the abundance of the
      repolarization reserve among the current and previous models may be in the order
      of the urethane-anesthetized guinea-pig heart>human intact ventricular
      tissue>halothane-anesthetized guinea-pig heart. Thus, the halothane-anesthetized
      guinea-pig model may be considered to be more sensitive than the previous models
      in predicting the QT-interval prolonging effects of new drugs in patients with
      high risks for the acquired long QT syndrome.

PMID- 16595930
TI  - Anti-complementary activity of ursane-type triterpenoids from Weigela
      subsessilis.
AB  - A new ursane-type triterpenoid, weigelic acid (1), and seven known compounds,
      ursolic acid (2), ilekudinol A (3), corosolic acid (4), ilekudinol B (5),
      esculentic acid (6), pomolic acid (7), and asiatic acid (8) were isolated from
      the leaf and stem of Weigela subsessilis. The structure of the new triterpenoid
      was established as 1beta,2alpha,3alpha,23-tetrahydroxyurs-12-en-28-oic acid on
      the basis of spectroscopic analyses. In addition, the isolated compounds were
      evaluated for their anti-complement activity against the classical pathway of the
      complement system. Of these, compounds 1-2 and 4-8 exhibited anti-complement
      activity with IC50 values of 152, 90, 130, 51, 56, 4, and 163 microM,
      respectively, whereas 3 was inactive. This shows that a carboxylic group of
      ursane-type triterpenoids seems to play an important role in inhibiting the
      hemolytic activity of human serum against erythrocytes.

PMID- 16595931
TI  - Melanogenesis stimulation in murine B16 melanoma cells by Kava (Piper
      methysticum) rhizome extract and kavalactones.
AB  - Melanogenesis stimulation activity of aqueous ethanolic extracts obtained from
      several different parts of five Piper species, namely Piper longum, P. kadsura,
      P. methysticum, P. betle, and P. cubeba, were examined by using cultured murine
      B16 melanoma cells. Among them, the extract of P. methysticum rhizome (Kava)
      showed potent stimulatory effect on melanogenesis as well as P. nigrum leaf
      extract. Activity-guided fractionation of Kava extract led to the isolation of
      two active kavalactones, yangonin (2) and 7,8-epoxyyangonin (5), along with three
      inactive kavalactones, 5,6-dehydrokawain (1), (+)-kawain (3) and (+)-methysticin
      (4), and a glucosylsterol, daucosterin (6). 7,8-Epoxyyangonin (5) showed a
      significant stimulatory effect on melanogenesis in B16 melanoma cells. Yangonin
      (2) exhibited a weak melanogenesis stimulation activity.

PMID- 16595932
TI  - Hepatoprotective compounds of the roots of Cudrania tricuspidata on tacrine
      induced cytotoxicity in Hep G2 cells.
AB  - The bioassay-guided fractionation of the MeOH extract of the root barks of
      Cudrania tricuspidata furnished three hepatoprotective compounds, gerontoxanthone
      A (2), cudraflavone B (4), gericudranin E (5), together with four prenylated
      xanthones, cudraxanthone B (3), isocudraxanthone K (6), cudraxanthone C (7),
      cudraxanthone H (8), and a prenylated flavanone, euchrestaflavanone C (1).
      Compounds 4 and 5 showed significant hepatoprotective effects with the EC50
      values of 37.39+/-0.4 and 39.87+/-0.7 microM, respectively, and compound 2 showed
      moderate hepatoprotective effect with an EC50 value of 125.9+/-1.5 microM,
      against tacrine-induced cytotoxicity in Hep G2 cells. Silybin as positive control
      showed an EC50 value of 84.76+/-0.5 microM. Isocudraxanthone K (6) is a new
      compound.

PMID- 16595933
TI  - Pharmacokinetic study of ketoprofen isopropyl ester-loaded lipid microspheres in
      rat blood using microdialysis.
AB  - A blood microdialysis technique coupled with high-performance liquid
      chromatography was used to investigate the pharmacokinetics of unbound ketoprofen
      in rats after intravenous administration of a lipid-soluble ketoprofen derivate,
      ketoprofen isopropyl ester (KPI), loaded into lipid microspheres (LM) and
      ketoprofen solution. A microdialysis probe was inserted into the jugular vein of
      male Wistar rats. KPI-loaded LM or ketoprofen solution (24 mg/kg, i.v.) was then
      administrated via a femoral vein. Dialysate samples were analyzed using HPLC. The
      in vitro and in vivo recovery rate of the microdialysis probe was 30.42+/-0.74%
      (n=3) and 40.27+/-2.74% (n=3), respectively. The pharmacokinetic parameters for
      ketoprofen after intravenous administration of KPI-loaded LM and ketoprofen
      solution exhibited no statistically significant differences. The results of this
      pharmacokinetic study indicate that the microdialysis technique can be widely
      applicable to investigations of in vivo free-drug of microcarrier systems.

PMID- 16595934
TI  - Transport of acebutolol through rabbit corneal epithelium.
AB  - The purpose of this study is to characterize transport of acebutolol through the
      corneal epithelium. Cultured normal rabbit corneal epithelial cells (RCEC) were
      used to investigate the drug transport. Primary RCEC were seeded on a filter
      membrane of Transwell-COL insert coated with fibronectin and were grown in
      Dulbecco's modified Eagle's medium/nutrient mixture F-12 with various
      supplements. Measurements of acebutolol permeability through RCEC layer were
      carried out to assess transcellular permeability coefficient (P(transcell)) in
      the absence or presence of inhibitors. Paracellular permeability coefficient
      (P(paracell)) was calculated by permeability coefficient of hydrophilic drugs
      (P(cell)). The transcellular permeability of acebutolol from apical side to basal
      side (A-to-B) showed concentration-dependency. The acebutolol flux in the A-to-B
      direction was smaller than that of opposite direction. Sodium azide, verapamil,
      and cyclosporin A enhanced the transcellular permeability of acebutolol in the A
      to-B direction. Acebutolol permeability through an excised rabbit cornea was also
      increased by verapamil. Thus, it was suggested that acebutolol was actively
      secreted via P-glycoprotein in a corneal epithelium.

PMID- 16595935
TI  - Proteases of a Bacillus subtilis clinical isolate facilitate swarming and
      siderophore-mediated iron uptake via proteolytic cleavage of transferrin.
AB  - We isolated a highly serine protease-producing Bacillus subtilis strain (PRY)
      from a clinical sample and identified it through biochemical testing and
      ribosomal DNA sequencing. The PRY strain exhibited a robust swarming behavior and
      was able to digest human transferrin efficiently, concomitantly with the
      production of catechol-siderophore in the exponential growth phase. The growth of
      PRY was in proportion to increased iron availability resulting from transferrin
      destruction. These results suggest that proteases of the B. subtilis PRY strain
      may play a significant role in the pathogenesis of human infections by
      facilitating siderophore-mediated iron uptake from transferrin and swarming
      motility.

PMID- 16595936
TI  - Effect of decrease in both postprandial blood glucose (PBG) and fasting blood
      glucose (FBG) levels in normal beagle dogs with nateglinide enteric coated
      granules and immediate release tablets.
AB  - Nateglinide is a new quick action/short duration (QRSD) type of oral blood
      glucose regulator, and nateglinide immediate release tablets are used for
      patients with mild diabetes under the trade name of Fastic((R)) tablets. In this
      study, we attempted to determine if it was possible to control both post-prandial
      blood glucose level (PBG) and fasting blood glucose level (FBG) for moderate or
      severe diabetes through controlled release of nateglinide. Enteric coated
      granules were selected for the administration form for controlled release of
      nateglinide, and three types of enteric coated granules were prepared having
      dissolution pH values of 5.5, 6.5 and 7.2. The three types of enteric coated
      granules were each administered separately or the enteric coated granules having
      an dissolution pH of 6.5 were administered simultaneous to administration of
      nateglinide immediate release tablets to normal beagle dogs just before feeding
      followed by measurement of plasma nateglinide concentration, plasma insulin
      concentration and blood glucose level. In the case of administering enteric
      coated granules alone (nateglinide: 9 mg/kg), the absorption of nateglinide was
      confirmed to tend to be delayed as the dissolution pH increased. In the case of
      an dissolution pH of 5.5, decreases in both PBG and FBG were observed. In the
      case of dissolution pH values of 6.5 and 7.2, only decrease in FBG was observed.
      In case of nateglinide immediate release tablets (nateglinide: 9 mg/kg), only
      decrease in PBG was observed. Decreases in both PBG and FBG were observed in the
      case of simultaneous administration of dissolution pH 6.5 enteric coated granules
      and nateglinide immediate release tablets just before feeding (nateglinide: 90
      mg/head+60 mg/head). A correlation was observed between plasma nateglinide
      concentrations and blood glucose levels. On the other hand, there were no
      correlations observed between changes in plasma insulin concentrations and blood
      glucose levels. In case of nateglinide immediate release tablets (nateglinide:
      150 mg/head), Decreases in both PBG and FBG were observed. However, the
      nateglinide controlled release formulation is more useful than the nateglinide
      immediate release tablets from the view point of avoidance of side effect, or of
      easy control of both PBG and FBG. On the basis of these results, the design of a
      controlled release formulation that contains nateglinide was suggested to enable
      control of both PBG and FBG for moderate and severe diabetes patients.

PMID- 16595937
TI  - Chemometric determination of naproxen sodium and pseudoephedrine hydrochloride in
      tablets by HPLC.
AB  - A new chemometric determination by high-performance liquid chromatography (HPLC)
      with photodiode array (PDA) detection was implemented for the simultaneous
      determination of naproxen sodium and pseudoephedrine hydrochloride in tablets.
      Three chemometric calibration techniques, classical least squares (CLS),
      principle component regression (PCR) and partial least squares (PLS) were applied
      to the peak area at multiwavelength PDA detector responses. The combinations of
      HPLC with chemometric calibration techniques were called HPLC-CLS, HPLC-PCR and
      HPLC-PLS. For comparison purposes the HPLC method called the classic HPLC method
      was used to confirm the results obtained from combined HPLC-chemometric
      calibration techniques. A good chromatographic separation between two drugs with
      losartan potassium as an internal standard was achieved using a Waters Symmetry
      C18 Column 5 microm 4.6+/-250 mm and a mobile phase containing 0.2 M acetate
      buffer and acetonitrile (v/v, 40:60). The multiwavelength PDA detection was
      measured at five different wavelengths. The chromatograms were recorded as a
      training set in the mobile phase. Three HPLC-chemometric calibrations and the
      classic-HPLC method were used to test the synthetic mixtures of naproxen sodium
      and pseudoephedrine hydrochloride in the presence of the internal standard. The
      HPLC-chemometric approaches were applied to real samples containing drugs of
      interest. The experimental results obtained from HPLC-chemometric calibrations
      were compared with those obtained by a classic HPLC method.

PMID- 16595938
TI  - Spectroscopic studies and life time measurements of binding of a bioactive
      compound to bovine serum albumin and the effects of common ions and other drugs
      on binding.
AB  - The mechanism of binding of anti-inflammatory drug, nimesulide (NIM) with bovine
      serum albumin (BSA) was investigated by fluorescence, absorption, circular
      dichroism (CD) and lifetime measurements under simulative physiological
      conditions. The analysis of fluorescence data indicated the presence of both
      dynamic and static quenching mechanism in the binding. Various binding parameters
      have been evaluated. The CD spectral data revealed the decrease in alpha-helical
      content of BSA from 70.9% (in free BSA) to 42.03% (in bound form) thereby
      indicating the conformational change in BSA upon binding. The binding of NIM to
      BSA was also confirmed by absorption spectra. Based on the Forster's theory of
      non-radiation energy transfer, the binding average distance, r between the donor
      (BSA) and acceptor (NIM) was found to be 2.17 nm. The association constants of
      NIM-BSA decreased in presence of the common ions and other drugs thereby
      indicating the availability of higher concentration of free drug (NIM) in plasma.

PMID- 16595939
TI  - Solubility prediction of paracetamol in binary and ternary solvent mixtures using
      Jouyban-Acree model.
AB  - The Jouyban-Acree model has been used to predict the solubility of paracetamol in
      water-ethanol-propylene glycol binary and ternary mixtures based on model
      constants computed using a minimum number of solubility data of the solute in
      water-ethanol, water-propylene glycol and ethanol-propylene glycol binary
      mixtures. Three data points from each binary solvent system and solubilities in
      neat solvents were used to calculate the binary interaction parameters of the
      model. Then the solubility at other binary solvent compositions as well as in a
      number of ternary solvents were predicted, and the mean percentage deviation (+/
      S.D.) of predicted values from experimental solubilities was 7.4(+/-6.1)%.

PMID- 16595940
TI  - Development and application of spectrophotometric methods for the determination
      of citalopram hydrobromide in dosage forms.
AB  - Study was carried out to develop two simple, fast, accurate and sensitive
      spectrophotometric methods (A and B) for the determination of citalopram
      hydrobromide in commercial tablet formulations. In method A, UV spectrophotometer
      determined the contents of citalopram hydrobromide in tablets at 240 nm in
      methanol solvent. The linear range was 5-40 microg ml-1 with molar absorptivity
      1.4x10(4) l mol-1 cm-1. While the method B based on the reaction of citalopram
      base as n-electron donor with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as pi
      acceptors to give highly colored complex species that absorb maximally at 590 nm.
      Beer's law was obeyed in the concentration limit of 10-250 microg ml-1 with molar
      absorptivity 3.3x10(3) l mol-1 cm-1 for citalopram hydrobromide. The limits of
      detection and limit of quantification was calculated and found to be 5.2 microg
      ml-1 and 17.4 microg ml-1 respectively. The proposed methods were found to be
      rapid, accurate, precise and sensitive for the determination of citalopram
      hydrobromide in commercial tablet formulations with out interferences from common
      additives encountered.

PMID- 16595941
TI  - Studies on the constituents of Scutellaria species (XXII). Constituents of the
      roots of Scutellaria amabilis HARA.
AB  - From the roots of Scutellaria amabilis HARA, eleven new flavonoids, 5,7,2'
      trihydroxy-8-methoxyflavone 7-O-beta-D-glucopyranoside, 5,7,2'-trihydroxy-8
      methoxyflavone 2'-O-beta-D-glucopyranoside, 5,7-dihydroxy-8,2'-dimethoxyflavone 7
      O-beta-D-glucopyranoside, 5,7,2'-trihydroxyflavone 2'-O-beta-D-glucopyranoside,
      5,7,2',5'-tetrahydroxyflavone 7-O-beta-D-glucuronopyranoside, (2S)-5,7,2',5'
      tetrahydroxyflavanone, (2S)-5,7,2',5'-tetrahydroxyflavanone 7-O-beta-D
      glucopyranoside, (2S)-5,7,2',5'-tetrahydroxyflavanone 7-O-beta-D
      glucuronopyranoside, (2S)-7,2'-dihydroxy-5-methoxyflavanone 7-O-beta-D
      glucuronopyranoside, (I-2S)-I-5,II-5,I-7,II-7,I-2',II-2',II-5'-heptahydroxy-[I
      6,II-6']-flavanonylflavone and (I-2S)-I-5,II-5,I-7,II-7,I-2',II-2',I-5',II-5'
      octahydroxy-[I-6,II-6']-flavanonylflavone, were isolated, together with ten known
      flavonoids, wogonin (5,7-dihydroxy-8-methoxyflavone), 5,7-dihydroxy-8,2'
      dimethoxyflavone, (2S)-5,7,2'-trihydroxyflavanone, scutevulin (5,7,2'-trihydroxy
      8-methoxyflavone), 5,7,4'-trihydroxy-8-methoxyflavone, alpinetin ((2S)-7-hydroxy
      5-methoxyflavanone), 5,7,2'-trihydroxyflavone, 5,7,2',5'-tetrahydroxyflavone,
      (2S)-7,2'-dihydroxy-5-methoxyflavanone and 5,7-dihydroxy-8,2'-dimethoxyflavone 7
      O-beta-D-glucuronopyranoside. The structures were determined on the basis of
      chemical and spectral data.

PMID- 16595942
TI  - A method for quantitative determination of furanocoumarins in capsules and
      tablets of phytochemical preparations.
AB  - A method for sample preparation and analysis by high-performance liquid
      chromatography with UV detection (HPLC-UV) was developed for analysis of
      psoralen, bergapten and 5-[3-(4,5-dihydro-5,5-dimethyl-4-oxo-2-furanyl)-butoxy]
      7H-furo[3-2-g][1]benzopyran-7-one in capsules and tablets employed in Brazil for
      certain illnesses. The linearity, accuracy, the inter- and intra-day precision of
      the procedure were evaluated. Analytical curves for furanocoumarins were linear
      in the range of 1.0-50.0 microg/ml. The recoveries of the furanocoumarins in the
      products analyzed were 97.3-99.5%, and the percent coefficient of variation for
      the quantitative analysis of the furanocoumarins in the analyses was under 5%.
      For inter-equipment study gas chromatography (GC) was employed.

PMID- 16595943
TI  - Afzeliixanthones A and B, two new prenylated xanthones from Garcinia afzelii
      ENGL. (Guttiferae).
AB  - Two new prenylated xanthones, afzeliixanthones A (1) and B (2), together with
      three known xanthones (3-5) and two phytosterols, beta-sitosterol and
      stigmasterol, were isolated from the CH2Cl2/MeOH (1:1) extract of the stem bark
      of Garcinia afzelii ENGL. collected in the South West Province of Cameroon.
      Structures were mainly established using one and two-dimensional NMR and mass
      spectroscopies. The antioxidant activities of the crude extracts as well as the
      new compounds (1) and (2) were evaluated.

PMID- 16595944
TI  - Structural scaffold of 18-crown-6 tetracarboxylic Acid for optical resolution of
      chiral amino acid: x-ray crystal analyses of complexes of D- and L-isomers of
      serine and glutamic acid.
AB  - (+)-18-crown-6 tetracarboxylic acid (18C6H4) has been used as a chiral selector
      for D/L-amino acids in HPLC, where L-isomer is usually eluted prior to D-isomer,
      except for the case of serine. To clarify why serine exhibits the reverse order
      for the elusion, the chiral interactions of D- and L-serines with (+)-18C6H4 were
      investigated by the X-ray single crystal analyses, together with the case of D-
      and L-glutamic acids, which exhibit the usual elution order in HPLC. The backbone
      structures (amino, Calpha-H and carboxyl groups) of these four amino acids showed
      the nearly same interaction with (+)-18C6H4 despite their different chirality. In
      contrast, the hydroxyl group of L-serine side chain formed a hydrogen bond with
      the carboxyl group of (+)-18C6H4, whereas such a interaction was not formed for
      the side chain of D-serine and D- and L-glutamic acids. Thus, it was shown that
      the exception of D/L-serine from the first elution rule of L-isomer in HPLC is
      due to the presence and absence of a hydrogen bond formation of its side chain OH
      group.

PMID- 16595945
TI  - Synthesis and antitumor evaluation of symmetrical 1,5-diamidoanthraquinone
      derivatives as compared to their disubstituted homologues.
AB  - A series of symmetrical 1,5-diamidoanthraquinone derivatives with potentially
      bioreducible groups has been synthesized and their cytostatic activity against
      the panel of various cancer cell lines in vitro has been studied. Preliminary
      structure-activity relationships were established. The results indicated that
      compounds 5 and 18 exhibited significant potent cytotoxicity at 1.24-1.75 microM
      for Hepa G2 cell line; compounds 5, 16, and 18 exhibited cytotoxicity at 0.14
      1.82 microM for 2.2.15 cell line as determined by XTT colorimetric assay. Two
      structurally related compounds, mitoxantrone and adriamycin, were tested in
      parallel as positive controls. In addition, it was found that compounds 5 and 18
      were a more potent and specific human hepatoma cell line than mitoxantrone and
      showed comparable activity to adriamycin. Among them, compound 18 was the most
      potent for 2.2.15 cells. We have demonstrated that the anthraquinone moiety is
      essential for activity and that less sterically hindered substituents contribute
      to enhanced in vitro efficacy. Implications for amidoanthraquinone cytotoxicity
      as potential anticancer agents are discussed. We further delineate the nature of
      the pharmacophore for this class of compounds, which provides a rational basis
      for the structure-activity relationships.

PMID- 16595946
TI  - Design and evaluation of jingzhiguanxin monolithic osmotic pump tablet.
AB  - A monolithic osmotic pump tablet (MOPT) of Traditional Chinese Medicine Compound
      Recipe (TCMCR) was successfully prepared and active components of Jingzhiguanxin
      prescription which has been widely used in China and Japan was selected as model
      drug. Analysis methods of maker compound in vitro of danshensu, paeoniflorin and
      safflor yellow A were built, and different methods were compared by f2 factors.
      The results showed that there were fine correlation among them. Finally UV method
      of safflor yellow A was chosen to determine the release of the drugs, which was
      fast, convenient, met the need of determination and could represent other
      methods. During the research, single factor influence selection was studied
      emphatically. It showed that there were significant influence between different
      varieties and quantity of osmotic promoting agents, different kind of retardants,
      different varieties and quantity of PEG (polyethylene glycol) and membrane
      weight. However, no significant influence existed between different quantity of
      retardants and SDS, different membrane orifices and methods of dissolution. Based
      on the single factor influence selection, an optimal formulation was decided, and
      three maker compounds of Jingzhiguanxin MOPT could isochronous release and at the
      same time they had good zero order release characteristics to 8 h. Paeoniflorin
      release in vivo was estimated by deconvolution, the results shown that there were
      a good in-vitro in-vivo correlation (r=0.9571).

PMID- 16595947
TI  - Synthesis and in vitro evaluation of iodinated derivatives of piperazine as a new
      ligand for sigma receptor imaging by single photon emission computed tomography.
AB  - A new series of radioiodinated analogues of 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3
      phenylpropyl)piperazine (SA4503) was synthesized and evaluated as a potential
      brain sigma-1 receptor imaging ligands by single photon emission computed
      tomography (SPECT). Iodinated analogues of SA4503 (4a-c) were prepared from
      piperazine in a high yield. The in vitro competition binding studies using [3H]
      DTG (sigma-1, 2), [3H] (+)-pentazocine (sigma-1), and [3H] DTG in the presence of
      carbetapentane (sigma-2) as sigma receptor selective radioligands were revealed
      that iodinated analogues 4a-c possess high affinities to sigma receptors (IC50:
      4a=7.1, 4b=31.0, and 4c=77.3 nM). In particular, the affinity of 4a, bearing
      iodine at ortho position on the phenyl ring, was 4.4 times greater than SA4503,
      and 3 times greater than that of haloperidol. The meta-iodo analogue 4b was the
      same to SA4503, the lead compound. The radioiodinated derivatives, [125I] 4a, 4b
      were synthesized no-carrier-added from the corresponding tributyltin precursors
      by the iododestannylation reaction with high yields. The binding of [125I] 4a, 4b
      have been characterized in the rat brain membranes. These compounds were
      indicated single population binding to sigma receptor with high affinity (4a:
      Kd=1.86+/-0.34 nM, Bmax=205+/-28.9 fmol/mg protein, 4b: Kd=3.30+/-0.51 nM,
      Bmax=231.5+/-13.8 fmol/mg protein). In vitro blocking studies were confirmed that
      the high specificity of 4a, 4b. These results suggest that radioiodinated 4a and
      4b are promising sigma receptors imaging ligand for pursuing further in vivo
      studies.

PMID- 16595948
TI  - Total synthesis of oxyfagaronine, phenolic benzo[c]phenanthridine and general
      synthetic way of 2,3,7,8- and 2,3,8,9-tetrasubstituted benzo[c]phenanthridine
      alkaloids.
AB  - Benzo[c]phenanthridine alkaloids such as oxynitidine, oxysanguinarine, oxyavicine
      and phenolic oxyfagaronine were synthesized from easily available starting
      benzonitriles 5 and toluamides 6 using a lithiated toluamide-benzonitrile
      cycloaddition reaction. The coupling reaction provided 3-arylisoquinolinones that
      were transformed to the benzo[c]phenanthridones. This method is highly efficient
      and could be useful for preparing diverse substituted aromatic
      benzo[c]phenanthridine compounds on a multi gram scale.

PMID- 16595949
TI  - Enhanced skin permeation of salicylate by ion-pair formation in non-aqueous
      vehicle and further enhancement by ethanol and l-menthol.
AB  - Enhancement of skin permeability of salicylate from non-aqueous vehicle by ion
      pair formation with either alkylamines or benzylamine as model cationic ions was
      examined in excised guinea pig dorsal skin. Solubility of salicylate in isopropyl
      myristate (IPM) was increased by the addition of either alkylamines or
      benzylamine as counter ions. The increase was more significant in the presence of
      amines with longer alkyl chains. Flux of salicylate increased in the presence of
      these amines due to the increase in the solubility. Maximum flux was observed in
      the presence of n-hexylamine, which induced an 11-fold increase due to 137-fold
      increase in solubility. Flux and permeability coefficients of salicylate in the
      presence of n-butylamine, n-hexylamine, iso-octylamine and benzylamine as counter
      ions in IPM were larger than those of the non-ionic form of salicylic acid. Flux
      of 3-methylsalicylate (3-CH3 substituent) and that of 5-hydroxysalicylate (5-OH
      substituent) were smaller than that of salicylate in the presence of n
      hexylamine. After partition to the skin surface, the ion-pair is suggested to
      dissociate and permeate separately according to the study using lidocaine as the
      counter ion. Flux of salicylate increased in the presence of benzylamine as the
      counter ion by the addition of 15% ethanol and 15% ethanol plus 1% l-menthol due
      to further improvement in the solubility as well as an increase in the
      permeability coefficient.

PMID- 16595950
TI  - Syntheses of model compounds related to an antigenic epitope in pectic
      polysaccharides from Bupleurum falcatum L. (II).
AB  - Stereocontrolled syntheses of model compounds related to a major antigenic
      epitope against antibupleurum 2IIc/PG-1-IgG from antiulcer pectic polysaccharide
      are described. A trisaccharide derivative (13) was prepared as a precursor and a
      novel and simple approach for the rational design of a glycocluster and
      glycodendrimer was developed, through the syntheses of the fluorescence-labeled
      glycocluster (2) and glycodendrimer (3).

PMID- 16595951
TI  - Direct determination of p-hydroxymethamphetamine glucuronide in human urine by
      high-performance liquid chromatography.
AB  - High-performance liquid chromatography (HPLC) with UV detection for the
      simultaneous determination of the free form of p-hydroxymethamphetamine (p-OHMA)
      and its metabolite, glucuronide (p-OHMAG) was accomplished for the first time. We
      achieved this by employing 1) an ion pair reagent for retention of sample to a
      solid-phase extraction (SPE) cartridge, Sep-Pak Light C18 and 2) a simple two
      step stepwise elution technique for subsequent ion pair RP-HPLC. The proposed
      method was optimized for resolution of p-OHMAG, p-OHMA and MA. The method was
      successfully applied to urine samples collected from MA abusers.

PMID- 16595952
TI  - Protective effects of a neutral polysaccharide isolated from the mycelium of
      Antrodia cinnamomea on Propionibacterium acnes and lipopolysaccharide induced
      hepatic injury in mice.
AB  - Mycelia of Antrodia cinnamomea were extracted with chloroform and hot water. A
      neutral polysaccharide named ACN2a separated from the water extract was purified
      using 10% CCl3COOH, and repeated column chromatography on HW-65 and DE-52
      cellulose. Its structure was determined by chemical and spectroscopic analyses.
      ACN2a was composed of Gal, Glc, Fuc, Man and GalN (in the ratio
      1:0.24:0.07:0.026:faint), in which an alpha-D-(1-->6)-Gal linkage accounted for
      73% of all linkages. The ratio of branch points was about 16% of the total
      residual numbers, and branches were attached to C-2 of galactosyl residues of the
      main chain. ACN2a had an average molecular weight of 12.9x10(5) Daltons,
      [alpha]D25=+115 degrees (c=0.44, H2O); [eta]=0.0417dl.g-1, Cp=0.2663 cal/(g.
      degrees C). The hepatoprotective effect of ACN2a was evaluated using a mouse
      model of hepatic injury that was induced by Propionibacterium acnes (P. acnes)
      and lipopolysaccharide (LPS). The administration of ACN2a (0.4, 0.8 g/kg/d,
      p.o.), significantly prevented increases in serum aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT) enzyme activities in mice treated with
      P. acnes-LPS, indicating hepatoprotective activity in vivo.

PMID- 16595953
TI  - Atomic force microscopic examination of chromosomes treated with trypsin or
      ethidium bromide.
AB  - Trypsin treatment is frequently used during chromosome preparation for removal of
      cellular contaminants, and ethidium bromide (EB) staining of bands is often used
      to facilitate high-resolution observations by optical microscopy. However,
      conventional optical microscopy is unable to visualize potential aberrations of
      chromosome structures caused by these physicochemical treatments. In this
      article, we use atomic force microscopy (AFM) in the tapping mode to obtain and
      analyze high-resolution images of chromosome surface structure damage associated
      with trypsinization and EB treatment. According to our results, the trypsin-based
      digestion effects became more severe as incubations increased across a range from
      10 to 40 s; a digestion time of 10 to 20 s appeared to be most suitable for
      observation by AFM. In terms of chromosomal damage induced by EB treatment,
      addition of EB into the media of cultured human blood cells induced chromosomal
      breakage in a dose-dependent fashion, and the results indicate centromeric region
      damnifyed severer than arms. Together, these results indicate that EB staining
      and the standard chromosomal preparative techniques of trypsinization can induce
      chromosomal damage that may affect the observed results.

PMID- 16595954
TI  - Bioactive constituents from Chinese natural medicines. XVII. constituents with
      radical scavenging effect and new glucosyloxybenzyl 2-isobutylmalates from
      Gymnadenia conopsea.
AB  - The methanol-eluted fraction of the methanolic extract from the tubers of
      Gymnadenia conopsea was found to show radical scavenging activities for DPPH and
      super oxide anion (.O2-) radicals. Three new glucosyloxybenzyl 2-isobutylmalates,
      gymnosides VIII, IX, and X, were isolated from this natural medicine together
      with 58 known constituents. The stereostructures of gymnosides were elucidated on
      the basis of chemical and physicochemical evidence. In addition, the phenanthrene
      and dihydrostilbene constituents showed radical scavenging activities and
      suggested the following structural requirements on radical scavenging activities;
      a) phenanthrenes: 1) dihydrogenation at the 9,10-positions enhances the
      activities, 2) the 1 or 3-p-hydroxybenzyl group enhances the activities; b)
      dihydrostilbenes: 1) methylation of the 3'-position reduces the activities, 2)
      the 2- and/or 6-p-hydroxybenzyl groups enhance the activities.

PMID- 16595956
TI  - Photooxidation of acyclovir with thermally generated triplet excited ketones. A
      comparison with type I and II photosensitizers.
AB  - The antiviral drug acyclovir (Ac, 1) was treated with triplet excited ketones,
      which have been generated in thermal decomposition of 3-(hydroxymethyl)-3,4,4
      trimethyl-1,2-dioxetane (HTMD), in the dark. Three major oxidation products were
      detected by means of spectroscopic measurements. The products were (2
      hydroxyethoxy) methyl spiroiminodihydantoin (2), (2-hydroxyethoxy) methyl (amino)
      2-imino-1,2-dihydroimidazole-5-one (3), and 2,2-diamino-4-[(2-hydroxyethoxy)
      methyl) amino)-5-[2H]-oxazolone (4). Equal amounts of type I and type II
      photooxidation products were found, as could be established by comparison with
      predominant type I (riboflavin) and type II (rose bengal) photosensitizers. The
      concentration and time profiles for the HTMD-induced oxidation of Ac were also
      determined. The participation of singlet oxygen in HTMD-induced oxidation was
      confirmed by the substantial D(2)O effect in the formation of
      spiroiminodihydantoin (2).

PMID- 16595955
TI  - Preparation of floating drug delivery system by plasma technique.
AB  - A novel intragastric floating drug delivery system (FDDS) has been prepared by
      pulsed plasma-irradiation on the double-compressed tablet of 5-Fluorouracil (5
      FU) as a core material with outer layer composed of a 68/17/15 weight ratio of
      Povidone (PVP), Eudragit RL (E-RL) and NaHCO3. The plasma heat flux caused the
      thermal decomposition of NaHCO3 to generate carbon dioxide and the resultant
      gases were trapped in bulk phase of outer layer, so that the tablets turned to
      have a lower density than the gastric contents and remained buoyant in simulated
      gastric fluid for a prolonged period of time. In addition, the release of 5-FU
      from the tablet is sustained by occurrence of plasma-induced crosslink reaction
      on the outer layer of tablet and the release rate of 5-FU can be well controlled
      by plasma operational conditions.

PMID- 16595957
TI  - Histidine-tagged shiga toxin B subunit binding assay: simple and specific
      determination of gb3 content in mammalian cells.
AB  - A two-step binding assay for globotriaosylceramide (Gb3) content was developed by
      histidine-tagging strategy, which is a well-established method for the
      purification of recombinant proteins. The complete binding of the recombinant His
      tagged Shiga toxin 1B subunit (1B-His) (1 microg/ml) to the standard Gb3 adsorbed
      on a multi-well H type plate was observed within 30 min at 37 degrees C; and its
      binding could be visualized by the following applications of HisProbe-HRP (8
      microg/ml) and tetramethylbenzidine (TMB) peroxidase substrate. The 1B-His
      binding assay was linear over the range of 1 to 100 ng of Gb3 per well. The
      binding of 1B-His was specific to Gb3 separated from HeLa cells, and no major
      cross-reactivity of other glycolipids in Folch's lower fractions extracted from
      HeLa cells was detected. The glycolipids in Folch's lower fractions from HeLa
      cells, human fibroblasts and mouse heart were suitable for this assay, but the
      further purification was needed for glycolipids from human plasma, thus sample
      preparation is critical factor for the reliable determination of Gb3 content. The
      1B-His binding to Gb3 was inhibited by the addition of galactose, but not
      mannose. This 1B-His binding assay will be useful not only for the determination
      of Gb3 content, but also for screening for the compounds which inhibit the toxin
      binding to Gb3. The strategy of our present method may be applicable for other
      binding assay, such as Cholera toxin B-subunit for ganglioside GM1.

PMID- 16595958
TI  - Molecular motions of alpha-cyclodextrin on a dodecyl chain studied by molecular
      dynamics simulations.
AB  - Motions of an alpha-cyclodextrin (alpha-CD) molecule on a dodecyl chain adopting
      the all-trans conformation were investigated in the presence of water by
      molecular dynamics simulations with CVFF force fields, where the
      trimethylammonium group of dodecyltrimethylammonium bromide (DTAB) is protruded
      outside the secondary hydroxyl rim of alpha-CD (the secondary-in structure). The
      alpha-CD molecule shuttled rapidly on the chain without decomplexation. This
      rapid motion is consistent with the NMR data. The plane formed by 6 O4 atoms of
      alpha-CD is most populated between the C6 and C7 atoms of DTAB. This structure is
      very close to that estimated by NMR. The alpha-CD molecule underwent a restricted
      rotation in a range of 60 degrees with regard to the plane of the dodecyl chain:
      this plane at the most population is middle between the two diagonal lines of the
      normal hexagon formed by 6 O4 atoms of alpha-CD. The published NMR data were
      reanalyzed in terms of the rotation angle, and a slightly better structure was
      obtained. The distortion of the alpha-CD cavity from the normal hexagon was
      decreased upon complex formation with DTAB. The deviation of the center of alpha
      CD from the center of the dodecyl chain predicted by molecular dynamics
      simulations is consistent with the NMR data. The secondary-in structure is
      energetically more stable than the primary-in structure, as calculated by
      molecular mechanics with CVFF and Amber force fields. This result is consistent
      with the NMR data. Molecular dynamics simulations were also carried out for the
      primary-in structure. Some of the results are close to those of the secondary-in
      structure.

PMID- 16595959
TI  - Ceanothane- and lupane-type triterpenes with antiplasmodial and antimycobacterial
      activities from Ziziphus cambodiana.
AB  - One new and eight known ceanothane- and lupane-type triterpenes were isolated
      from the root bark of Ziziphus cambodiana PIERRE (Rhamnaceae). Based on spectral
      analyses, the structure of the new compound was elucidated as 3-O-(4-hydroxy-3
      methoxybenzoyl)ceanothic acid (3-O-vanillylceanothic acid) (1), while the known
      compounds were identified as lupeol (2), betulinaldehyde (3), betulinic acid (4),
      2-O-E-p-coumaroyl alphitolic acid (5), alphitolic acid (6), zizyberanalic acid
      (7), zizyberenalic acid (8) and ceanothic acid (9). Compounds 1, 5 and 8
      exhibited significant in vitro antiplasmodial activity against the parasite
      Plasmodium falciparum, with inhibitory concentration (IC50) values of 3.7, 0.9
      and 3.0 microg/ml, respectively. Compounds 1 and 3-8 showed antimycobacterial
      activity against Mycobacterium tuberculosis with respective MIC values of 25, 25,
      25, 12.5, 50, 50 and 100 microg/ml.

PMID- 16595960
TI  - Hyosgerin, a new optically active coumarinolignan, from the seeds of Hyoscyamus
      niger.
AB  - Hyosgerin, a new optically active coumarinolignan, has been isolated and
      characterized along with three other coumarinolignans, venkatasin, cleomiscosin A
      and cleomiscosin B, from the seeds of Hyoscyamus niger L. The structure was
      determined on the basis of spectroscopic analysis and chemical conversion. The
      optical properties and absolute stereochemistry of these coumarinolignans have
      also been studied and discussed.

PMID- 16595961
TI  - A new triterpene and dibenzocyclooctadiene lignans from Schisandra propinqua
      (WALL.) BAILL.
AB  - A new triterpene and two new natural dibenzocyclooctadiene lignans were isolated
      from the stems of Schisandra propinqua. In addition, three known lignans,
      octadecanoic acid, 2,3-dihydroxypropyl ester and beta-sitosterol were isolated.
      The structures of the new triterpene and new natural products were elucidated
      base on spectral analysis, including 1D and 2D NMR experiments. The isolates were
      tested for their cytotoxic effects against several tumor cell lines by MTT assay.

PMID- 16595962
TI  - Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia
      dulcis of Vietnamese origin.
AB  - From the aerial parts of Scoparia dulcis L. (Scrophulariaceae) grown in Vietnam,
      four scopadulane-type diterpenoids (4-7), of which 7 is new and was given the
      trivial name scopadulcic acid C, together with nine known compounds were
      isolated. Their structures were elucidated by spectroscopic analyses. The
      absolute configurations of 4-7 were ascertained by applying the modified Mosher's
      method to iso-dulcinol (6). The isolation of the lignans nirtetralin and
      niranthin for the first time from S. dulcis is also of chemotaxonomic interest.
      The cytotoxic activity in KB cells, inhibitory effect on LPS/IFNgamma-induced NO
      production, inhibition of multidrug resistance (MDR), and antibacterial and
      antifungal activities of the scopadulane-type diterpenoids 4-7 were examined in
      this study.

PMID- 16595963
TI  - Nine constituents including six xanthone-related compounds isolated from two
      ascomycetes, Gelasinospora santi-florii and Emericella quadrilineata, found in a
      screening study focused on immunomodulatory activity.
AB  - Five metabolites tentatively called GS-1 (1)-5 (5) from Gelasinospora santi
      florii, and four tentatively called EQ-4 (6), EQ-6 (7)-8 (9) together with 1-4
      from Emericella quadrilineata have been isolated in a screening study on
      immunomodulatory fungal constituents. Among these nine metabolites, EQ-7 and 8
      have been unknown. This time, the structures of GS-4 which has previously been
      isolated, EQ-7, and -8 have been determined to be (4R,4aS,9aR)-1,9a
      dihydronidulalin A (4), (4S,4aR,9aR)-4a-carbomethoxy-1,4,4a,9a-tetrahydro-4,8
      dihydroxy-6-methylxanthone (8), and 9-hydroxymicroperfuranone (9), respectively,
      and the six other metabolites have been identified. On bioassay, a
      dihydroxanthone, nidulalin A (1), a hexaketide, sordarial (5), and a xanthone,
      pinselin (7) have displayed significant immunosuppressive activities. The
      structure-activity relationships of these constituents have also been discussed.

PMID- 16595964
TI  - Reduction of 1,4-dien-3-one steroids with LiAl2H4 or NaB2H4: stereospecific
      deuterium-labeling at the c-1alpha position of a 4-en-3-one steroid.
AB  - Reduction of a double bond at C-1 of 1,4-dien-3-one steroids 7 and 8 with LiAl2H4
      in THF or NaB2H4 in MeOH and H2O gave stereospecifically [1alpha-2H]-labeled 4-en
      3-one steroids 9 and 10, respectively. When the deuterated solvents, MeO2H and
      2H2O, were used for the reaction of steroid 8 with NaB2H4, [1alpha,2xi-2H2]
      labeled compound 10 was produced. This indicates that the reaction proceeds
      through the initial hydride attack at the C-1alpha position, followed by
      ketonization of the 2-en-3-ol intermediate.

PMID- 16595965
TI  - Five new triterpenoid saponins from the roots of Platycodon grandiflorum.
AB  - Five new triterpenoid saponins, platycoside H [3-O-beta-D-glucopyranosyl-(1-->6)
      beta-D-glucopyranosyl-2beta,3beta,16alpha,23-tetrahydroxyolean-12-en-28-oic acid
      28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranoside], platycoside I [3-O-beta-D-glucopyranosyl-(1-->6)-beta-D
      glucopyranosyl-(1-->6)-beta-D-glucopyranosyl-2beta,3beta,16alpha,23
      tetrahydroxyolean-12-en-28-oic acid 28-O-beta-D-xylopyranosyl-(1-->4)-alpha-L
      rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside], platycoside J [3-O-beta-D
      glucopyranosyl-2beta,3beta,16alpha,23-tetrahydroxyolean-12-en-28-oic acid 28-O
      beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranoside], platycoside K [3-O-beta-D-glucopyranosyl-(1-->3)-beta-D
      glucopyranosyl-2beta,3beta,16alpha,23,24-pentahydroxyolean-12-en-28-oic acid],
      and platycoside L [3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl
      2beta,3beta,16alpha,23,24-pentahydroxyolean-12-en-28 oic acid], and three known
      triterpenoid saponins, platycoside F, platycoside B, and platycoside C, were
      isolated from the roots of Platycodon grandiflorum A. DC. Their chemical
      structures were elucidated on the basis of their spectral data and chemical
      evidence.

PMID- 16595966
TI  - Calorimetry and cryo-transmission electron microscopic studies of PEG2000-grafted
      liposomes.
AB  - The phase behavior of poly(ethylene glycol) grafted liposomes (PEG-liposomes) was
      investigated by differential scanning calorimetry (DSC), dynamic light scattering
      (DLS) and cryo-transmission electron microscopy (cryo-TEM). PEG-liposomes were
      prepared from mixtures of dipalmitoyl phosphatidylcholine (DPPC) and distearoyl
      phosphatidylethanolamine with a covalently attached PEG molecular weight of 2000
      (DSPE-PEG2000). From the results of DLS measurements, the coexistence of PEG
      liposomes and small molecular assemblies were confirmed at mole fractions of DSPE
      PEG2000 above about 0.1. Moreover, it was confirmed that small molecular
      assemblies were disk micelles by cryo-TEM. However, the phase transition
      enthalpies of PEG-liposomes were hardly changed according to the DSC measurement,
      though the mole fraction of the PEG lipid increased. From these results, it was
      suggested that the phase transition enthalpies hardly changed despite mixed
      micelles being formed because the bilayer structure of the disk micelle maintains
      high cooperativity between the DPPC molecules.

PMID- 16595967
TI  - Spectrofluorimetric determination of paroxetine hydrochloride in its formulations
      and human plasma.
AB  - A sensitive spectrofluorimetric procedure for the determination of paroxetine-HCl
      in pharmaceutical formulations and human plasma has been described. The native
      fluorescence of the drug has been studied under different conditions. Maximum
      fluorescence intensity was obtained in methanol at 340 nm using 290 nm for
      excitation. Different surfactants showed negative effect on the fluorescence
      intensity of paroxetine-HCl. Regression analysis of Beer's plot showed good
      correlation (r=0.9999) between fluorescence intensity and concentration over the
      range of 0.05-0.40 microg ml-1 with lower limit of detection (LOD) of 0.015
      microg ml-1. The drug was successfully determined in its tablets with average %
      recovery of 98.00+/-0.99% which was in accordance with those given by a
      compendial method. The method was also applied to the determination of paroxetine
      HCl in spiked human plasma with average recovery of 77.70+/-1.06%.

PMID- 16595968
TI  - Three novel triterpenoid saponins from Lysimachia capillipes and their cytotoxic
      activities.
AB  - Three new saponins, capilliposide A (1), capilliposide B (2) and capilliposide C
      (3) were isolated from an ethanol extract of Lysimachia capillipes. Their
      structures were determined by 1D and 2D NMR (1H-1H COSY, HMBC, HMQC, DEPT and
      TOCSY) techniques, MS, and hydrolysis. Capilliposide B showed significant
      cytotoxicity against human A-2780 cells.

PMID- 16595969
TI  - Four new isoflavonoids from the stem bark of Erythrina variegata.
AB  - Bioassay-directed fractionation of the stem bark extract of Erythrina variegata
      L. has resulted in the isolation of three new isoflavones: 5,4'-dihydroxy-8-(3,3
      dimethylallyl)-2''-methoxyisopropylfurano[4,5:6,7]isoflavone (1), 5,7,4'
      trihydroxy-6-(3,3-dimethylallyloxiranylmethyl)isoflavone (2), 5,4'-dihydroxy-8
      (3,3-dimethylallyl)-2''-hydroxymethyl-2''-methylpyrano[5,6:6,7]isoflavone (3) and
      a new isoflavanone, 5,4'-dihydroxy-2'-methoxy-8-(3,3-dimethylallyl)-2'',2''
      dimethylpyrano[5,6:6,7]isoflavanone (4) together with seven known compounds,
      euchrenone b10 (5), isoerysenegalensein E (6), wighteone (7), laburnetin (8),
      lupiwighteone (9), erythrodiol (10), and oleanolic acid (11). The structures were
      determined on the basis of spectroscopic analyses and chemical evidence. The
      effect of these compounds on the proliferation of rat osteogenic sarcoma (UMR106)
      is also reported.

PMID- 16595970
TI  - Abietane diterpenoids from the barks of Cryptomeria japonica.
AB  - From the bark of Cryptomeria japonica were isolated sugikurojins I (1) and J (2),
      and an abietane derivative (3) was obtained for the first time as a natural
      product. These structures were elucidated primarily through extensive NMR
      experiments. Sugikurojin I (1) has a unique skeleton incorporating an abietane
      diterpene and a 1,10-secocadinane sesquiterpene. Sugikurojin J (2) is a
      peroxyester of hydroxyabietane diterpene and isopimarane acid diterpene. Compound
      3 was p-quinone acid, which occurred by cleavage between C-7 and C-8 of sugiol;
      it was deduced to [4'-isopropyl-1(S),3,3-trimethyl-3',6'-dioxo-bicyclohexyl-1',4'
      dien-2(R)-yl]-acetic acid. Also obtained in this investigation were three known
      diterpenes (4-6).

PMID- 16595971
TI  - Bisanthraquinone metabolites produced by the endophytic fungus Diaporthe sp.
AB  - Two bisanthraquinones named (+)-epicytoskyrin (1) and (+)-1,1'-bislunatin (2)
      were produced by the endophytic fungus from a tea plant, which is a species
      closely related to Diaporthe phaseolorum strain sw-93-13. The chemical structures
      of the metabolites were elucidated on the basis of the physicochemical properties
      including the circular dichroism (CD) spectrum.

PMID- 16595972
TI  - QSAR study of 3-phenyl-5-acyloxymethyl-2H,5H-furan-2-ones as antifungal agents:
      the dominant role of electronic parameter.
AB  - To explore physicochemical properties of 3-phenyl-5-acyloxymethyl-2H,5H-furan-2
      ones derivatives responsible for their antifungal activity, a quantitative
      structure activity relationship, Hansch approach was applied on sixteen compounds
      of above mentioned derivatives. Various physicochemical descriptors and reported
      minimum inhibitory concentration values of different fungal organisms were used
      as independent variables and dependent variable respectively. The best models for
      twelve different fungal organisms were first validated by leave-one-out cross
      validation procedure. Further, bootstrapping method was adopted to assess the
      robustness of the models. It was revealed that electronic parameters were found
      to have overall significant correlation with antifungal activity and these
      studies provide an insight to design new molecules.

PMID- 16595973
TI  - Simultaneous determination of components in preparation Naodesheng injection by
      high performance liquid chromatograph-atmospheric pressure chemical ionization
      mass spectrometry (HPLC-MS/APCI).
AB  - A high-performance liquid chromatograph with mass spectrum detection (HPLC
      MS/APCI) method has been established for simultaneous determination of ten major
      bioactive components of Naodesheng injection including safflor yellow A,
      puerarin, daidzein, ginsenosides (Rg1, Rg2, Rb1, Rd, Re, Rh1), and
      notoginsenoside R1. The separations were carried out with a Luna C18 column (5
      microm, 150x4.6 mm, Phenomenex, U.S.A.) with a stepwise gradient elution of the
      mobile phase consisting of water (0.1% of formic acid, v/v)-methanol (0 min,
      70:30; 8 min, 30:70; 20 min, 10:90) at a flow-rate of 0.8 ml/min. The proposed
      method was applied to analyze five various Naodesheng injections and produced
      data with acceptable linearity, repeatability, precision and accuracy having
      lower limits of quantitation (LLOQs) of 0.02-0.2 microg. The calibration curves
      were linear in respective range for all compounds, all of them with coefficients
      of determination above 0.9900. The intraday precessions were less than 5.0%. The
      proposed method is accurate, sensitive and simple, a useful alternative for
      routine analysis in the quality control of Traditional Chinese Medicine.

PMID- 16595974
TI  - Recyclable polymeric pi-acid catalyst effective on Mannich-type reaction in
      water.
AB  - Polymer-supported dicyanoketene acetal (poly-DCKA-1), synthesized by
      copolymerization of a DCKA bearing a 4-vinylbenzyl group with ethyleneglycol
      dimethacrylate, was found to be an excellent recyclable catalyst for the three
      component Mannich-type reaction of aldehydes, aromatic amines, and TMS enolate of
      ethyl isobutyrate in water as the sole solvent.

PMID- 16595975
TI  - [Appetite regulation by NPY and its related neuropeptides].

PMID- 16595976
TI  - [Thyroid hormone and various other hormones regulate hypothalamic neuropeptide Y
      (NPY) expression and feeding behavior].

PMID- 16595977
TI  - [Ghrelin-neuropeptide Y axis in the control of feeding and gastrointestinal
      motility].

PMID- 16595978
TI  - [Development of anorectic NPY antagonists: possible roles of Y1 and Y5 receptors
      in feeding regulation].

PMID- 16595979
TI  - [Regulation of hypothalamic neuropeptide expression and feeding behavior in NPY
      Y5 knockout (KO) mice].

PMID- 16595980
TI  - [The hibernation control system: a new biomedical field developed by hibernation
      research].

PMID- 16595981
TI  - [Progress in the research on Lox-1 and its clinical relevance].

PMID- 16595982
TI  - [Evaluation of drugs for the treatment of atopic dermatitis in mice].

PMID- 16595983
TI  - Edaravone in acute ischemic stroke.

PMID- 16595984
TI  - Prognostic factors in diffuse large B-cell lymphoma.

PMID- 16595985
TI  - Clinical aspects of hepatocellular carcinoma in Japan.
AB  - HCC in Japan has very different characteristics from that in other Asian
      countries. Because, among the Japanese HCC patients approximately 80% of the
      patients are HCV positive and they are aged over 60 years old. On the other hand,
      in many Asian countries HBVpositive HCC patients are dominant and their age is
      younger than the Japanese patients. Early diagnosis of HCC is mainly performed by
      means of imaging diagnostic technique such as abdominal ultrasonography, dynamic
      CT, dynamic MRI and CT angiography. If small HCC less than 3 cm in diameter is
      found and liver function is well preserved, local ablation therapy or surgical
      treatment promises better than 5 years survival (over 60%). While, TAE or TACE is
      performed in cases of HCC larger than 3 cm in size, if liver failure is not
      complicated. In advanced HCC cases with multiple tumors, arterial infusion of
      anticancer drug has been applied. However, its efficacy is not estimated.
      Chemoprevention is another modality for HCC. Eradication of HCV with an antiviral
      agent has proven to prevent hepatocarcinogenesis. As for chemoprevention of HCC,
      some trials are on going in Japan.

PMID- 16595986
TI  - Risk factors and the incidence of coronary artery disease in young middle-aged
      Japanese men: results from a 10-year cohort study.
AB  - OBJECTIVE: The objective of this study was to elucidate the relationship between
      risk factors and the coronary artery disease (CAD) in young middle-aged Japanese
      men. METHODS: A cohort study of 2,764 young middle-aged Japanese men aged 3544
      (mean+/-SD: 42.3+/-2.5) years based on a 10-year followup to identify the risk
      factors for the occurrence of CAD was conducted. There were 35 cases of CAD
      during the follow up; 25 myocardial infarctions and 10 angina pectoris. The Cox
      Proportional hazard model was used to identify the independent risk factors for
      CAD. Adjustment was made for variables including age, body mass index, smoking
      habit, systolic blood pressure, total cholesterol (TC), high-density lipoprotein
      cholesterol (HDLC), fasting plasma glucose (FPG), and triglyceride. RESULTS: TC,
      low HDLC, and FPG were identified as significant independent risk factors for
      CAD. Adjusted hazard ratio (HR) of a high level of TC> or = 220 (mg/dl) for CAD
      was 5.46 (95% confidence interval (CI): 1.9617.51) and that of a high level of
      HDLC<50(mg/dl) was 9.01 (95%CI: 1.1372.17), and a high level of FPG> or = 110
      (mg/dl) was 2.94 (95%CI: 1.228.23). Considering the combination of these risk
      factors, adjusted HR for CAD of the subjects who had 2 risk factors was 8.37
      (95%CI: 2.2131.65). CONCLUSIONS: Using the database of young middle-aged Japanese
      men, TC, low HDLC, and FPG were found to be important risk factors for CAD, and
      the combination of these risk factors was associated with CAD.

PMID- 16595987
TI  - Gender difference in the level of high-density lipoprotein cholesterol in elderly
      Japanese patients with coronary artery disease.
AB  - OBJECTIVE: High-density lipoprotein cholesterol (HDLC) levels are known to be
      reduced in the metabolic syndrome, but the HDLC profile of elderly patients with
      coronary artery disease (CAD) has not been well characterized. This study
      investigated the gender difference of HDLC levels in elderly Japanese patients
      with CAD. METHODS: Serum lipid data were analyzed retrospectively to assess sex
      related differences of the lipid profile, and to evaluate the effects of
      pharmacotherapy or physical exercise on hyperlipidemia. PATIENTS: A total of 163
      elderly (> or = 65 years) outpatients with CAD (128 men aged 70.6+/-5.2 years and
      35 women aged 74.1+/-6.0 years [mean+/-SD]) were investigated. RESULTS: The mean
      total cholesterol (TC), low-density lipoprotein cholesterol (LDLC), and
      triglyceride (TG) levels were similar in men and women, while the mean HDLC level
      was significantly higher in women than men (58.3+/-18.1 vs. 50.3+/-13.5 mg/dL;
      p=0.0064). The HDLC level was not significantly influenced by oral lipid-lowering
      therapy or regular exercise in either sex. However, women without lipid-lowering
      therapy had significantly higher HDLC levels than men with (p=0.0312) or without
      (p=0.0338) lipid-lowering therapy, while women performing regular exercise had
      significantly higher HDLC levels than men with (p=0.0047) or without (p<0.001)
      regular exercise. CONCLUSION: Elderly women with CAD have higher HDLC levels
      relative to their postmenopausal state than those of men with CAD. Low HDLC
      levels, unlike in men, may not be a major risk factor for CAD in elderly women.

PMID- 16595988
TI  - Prognostic factors in diffuse large B-cell lymphoma treated by risk-adopted
      therapy.
AB  - OBJECTIVE: The International Prognostic Index (IPI) was reported in 1993 and it
      is now widely used for predicting the outcome in patients with aggressive non
      Hodgkin's lymphoma. It defines 5 risk factors and 4 distinct risk groups from
      retrospective data. In this study, we evaluated the outcome of risk-adopted
      therapy for diffuse large B-cell lymphoma (DLBCL), the most common aggressive
      lymphoma, and assessed the possible prognostic factors. METHODS AND PATIENTS: We
      treated 177 consecutive patients newly diagnosed with DLBCL using therapies
      determined by putative risk factors. Therapies included CHOP followed by involved
      field irradiation; ACOMPB with the consolidation regimen MLY9; high-dose
      chemotherapy supported by autologous peripheral blood stem cell transplantation;
      or performance status (PS) oriented CHOP. Statistical analysis was performed to
      determine the comprehensive risk factors in DLBCL. RESULTS: Overall, the complete
      response (CR), 3-year overall survival (OS), and 3-year relapse-free survival
      (RFS) rates for CR patients were 71%, 69%, and 75%, respectively. Male gender,
      high LDH, poor PS (> or = 2), more than one extranodal involvement site, and B
      symptoms were independent adverse prognostic factors for OS. High LDH and poor PS
      were independent, adverse prognostic factors for RFS. CONCLUSION: In the 5 risk
      factors indicated by IPI, high LDH and poor PS remained for OS and RFS even after
      risk-adopted therapy.

PMID- 16595989
TI  - Efficacy of edaravone in cardioembolic stroke.
AB  - OBJECTIVE: We investigated the efficacy of edaravone in patients with
      cardioembolic stroke. METHODS: Cardioembolic stroke patients were treated with
      drip intravenous infusion of edaravone (ED group, n=141) for 7 days, and were
      retrospectively compared with a historical-controlled cohort of similar patients
      (control group, n=114). RESULTS: Early improvement (between day 0 and day 10),
      defined as change in National Institutes of Health Stroke Scale (NIHSS), was seen
      more frequently in mild patients (NIHSS on admission < or = 7) among the ED group
      than in the control group (change in NIHSS +2 vs. -2, respectively, p=0.013).
      Similar efficacy was not seen in the moderate to severe (NIHSS >7) patients.
      Independent patients (modified Rankin Scale < or = 2) 6 months after the onset
      were likely to be less frequent in the ED than the control group (28% versus 41%;
      p=0.066). Other clinical outcomes in the ED group were not significantly
      different from those in the control group. CONCLUSION: The results suggest that
      edaravone may only be effective in mild patients with cardioembolic stroke.

PMID- 16595990
TI  - Micafungin, a novel antifungal agent, as empirical therapy in acute leukemia
      patients with febrile neutropenia.
AB  - OBJECTIVE: Invasive fungal infection is a major cause of morbidity and mortality
      in patients with febrile neutropenia unresponsive to antibacterial treatment.
      Empirical antifungal therapy with amphotericin B has been the standard of care
      for these patients; however, there remains a need for less toxic alternative
      drugs. PATIENTS AND METHODS: We conducted a prospective study to evaluate the
      efficacy and safety of micafungin (MCFG), a novel antifungal agent of the
      echinocandin class, in an empirical therapy setting for patients with febrile
      neutropenia. RESULTS: A total of 31 patients with acute leukemia who developed
      febrile neutropenia were enrolled in the study. Among them, 18 patients
      fulfilling the protocol-defined criteria, including 10 with persistent fever and
      8 with recurrent fever, received MCFG empirically. Underlying diseases consisted
      of acute myeloid leukemia (n=15) and acute lymphoblastic leukemia (n=3). The
      median duration of neutropenia and drug administration was 22 and 9.5 days,
      respectively. Treatment success, defined as defervescence during the neutropenic
      period, absence of breakthrough fungal infections, and requiring no replacement
      of antifungal drugs, was achieved in 14 patients (78%). None of the patients
      required discontinuation or dose reduction due to adverse events except for one
      patient with severe hypokalemia. CONCLUSIONS: Although the studied patients were
      limited in number, our results indicate that MCFG is an encouraging agent for
      empirical antifungal therapy in patients with febrile neutropenia, and deserves
      further investigation in large-scale studies.

PMID- 16595991
TI  - A novel mutation in the von Hippel-Lindau tumor suppressor gene identified in a
      Japanese family with pheochromocytoma and hepatic hemangioma.
AB  - Von Hippel-Lindau (VHL) syndrome is a neoplastic syndrome caused by a mutation in
      the VHL gene. There is a discrepancy between the phenotypes of human VHL syndrome
      and VHL gene-disrupted mouse models. A heterozygous VHL gene-disrupted model (vhl
      +/-) developed hepatic vascular lesions; in contrast, hepatic hemangioma is a
      rare manifestation of human VHL syndrome. We identified a novel mutation (P154S)
      in the VHL gene in a Japanese family with pheochromocytoma. One of the members
      demonstrated hepatic hemangiomas, suggesting that there may be a relationship
      between the mutation of the VHL gene and hepatic vascular lesions, even in
      humans.

PMID- 16595992
TI  - Correction of copper deficiency improves erythropoietin unresponsiveness in
      hemodialysis patients with anemia.
AB  - We have encountered five hemodialysis patients who had received enteral nutrition
      and recovered from erythropoietin-resistant anemia with neutropenia after the
      correction of copper deficiency. We reduced the required doses of recombinant
      human erythropoietin (rHuEPO) to maintain the target hematocrit levels and three
      patients were finally weaned from the rHuEPO therapy. Thus, copper deficiency is
      involved in erythropoietin-resistant anemia in hemodialysis patients.

PMID- 16595993
TI  - Tuberous sclerosis complex complicated by pulmonary multinodular shadows.
AB  - A 41-year-old woman with a history of epilepsy was referred for multiple nodular
      ground-glass opacities on a chest computed tomography (CT) scan. They were
      initially suspected of representing atypical adenomatous hyperplasia or well
      differentiated adenocarcinoma. However, the subsequent brain CT and magnetic
      resonance imaging (MRI) scans revealed a coarse nodular calcification and
      cortical tubers. A subungual fibroma was also noted. Histological examination of
      a video-assisted thoracoscopic lung biopsy specimen disclosed multiple nodules of
      type II pneumocyte hyperplasia with septal thickening. Based on all of these
      findings taken together, a diagnosis of tuberous sclerosis complex with
      multifocal micronodular pneumocyte hyperplasia (MMPH) was made.

PMID- 16595994
TI  - Sarcoidosis associated with renal masses on computed tomography.
AB  - A 50-year-old woman was admitted to our hospital after computed tomography (CT)
      revealed renal masses and mediastinal lymphadenopathy. Uveitis had previously
      been diagnosed by a local ophthalmologist. Elevated levels of serum soluble IL2
      receptor were observed. However, renal function was not compromised. Abdominal CT
      showed multiple low attenuation tumor-like nodules in both kidneys. As lymphoma
      was considered likely, CT-guided renal biopsy was performed; however,
      histological examination of the excised specimens revealed noncaseating
      granulomas. Analysis of bronchoalveolar lavage fluid demonstrated a sarcoidosis
      pattern. The final diagnosis was sarcoidosis with renal involvement.

PMID- 16595995
TI  - Three cases of the nodular pulmonary amyloidosis with a longterm observation.
AB  - Longterm observation with chest radiograph and computed tomography (CT) scan was
      performed for pulmonary amyloidosis. There are few reports of primary pulmonary
      amyloidosis with a longterm observation. We encountered three cases of nodular
      pulmonary amyloidosis observed by intermittent chest radiograph or CT for 5 years
      or more. The patients were a 54-year-old man, and 67- and 68-year old women. For
      diagnosis, transbronchial biopsy and percutaneous lung biopsy were performed.
      Amyloid nodules grew slowly and two cases showed findings of cavity and
      calcification.

PMID- 16595996
TI  - Synchronus presentation of early-stage small cell carcinoma and adenocarcinoma in
      the same lung lobe.
AB  - A 73-year-old man with no symptoms was admitted to our hospital with a nodular
      shadow (>2 cm) in the left upper lung field on chest X-ray. A histological
      diagnosis (small cell carcinoma) was obtained by bronchoscopic examination
      including a transbronchial lung biopsy (TBLB). The preoperative clinical staging
      was T1N0M0 (StageIA). After preoperative chemotherapy (CDDP + CPT11) was carried
      out, a nodule in the left S(1+2) diminished remarkably, but a smaller nodule in
      the left S3 (>8 mm) remained unchanged. While the nodule in the left S(1+2)
      (small cell carcinoma) had become completely necrotic by the time the final
      diagnosis was made after resection of the left upper lobe, histological diagnosis
      of the nodule in the left S3 revealed a well differentiated adenocarcinoma.
      Synchronous presentation of early-stage lung cancer consisting of small cell
      carcinoma and adenocarcinoma was identified in the same left upper division of
      the lung. Because there have been the few previous reports regarding cases of
      synchronous presentation of early-stage lung cancer in the same lung lobe, we
      also report on the clinical characteristics, thus adding this case to the five
      previously reported cases.

PMID- 16595997
TI  - Pneumoconiosis associated with an esophageal ulcer and uptake revealed in FDGPET.
AB  - A 76-year-old man with a past history of pneumoconiosis visited the Department of
      Gastroenterology in our hospital suffering from dysphagia. Gastroscopy revealed
      an esophageal ulcer on the top of a torus lesion. Chest computed tomography (CT)
      revealed it was caused by a swollen lymph node in the mediastinum. Squamous cell
      carcinoma related antigen (SCC) was elevated to 1.8 ng/ml. To rule out
      malignancy, we performed fluorine-18 deoxyglucose positron emission tomography
      (FDGPET) which revealed a significantly increased uptake in a nodular lesion in
      the right upper lobe and mediastinal lymph nodes. Biopsy and cytology of the
      nodular lesion revealed only pneumoconiosis. We must be careful when we interpret
      the findings of FDGPET in pneumoconiosis patients.

PMID- 16595999
TI  - Secondary hemophagocytic syndrome in a patient with methicillin-sensitive
      Staphylococcus Aureus bacteremia due to severe decubitus ulcer.
AB  - A 51-year-old man with poliomyelitis was admitted to emergency because of a
      severe decubitus ulcer on his right hip that was associated with infection. His
      general condition deteriorated and he was malnourished and dehydrated. Despite
      adequate hyperalimentation and antibiotic administration, laboratory data
      indicated pancytopenia 4 days later. He was diagnosed as having secondary
      hemophagocytosis (HPS) associated with methicillin-sensitive Staphylococcus
      aureus sepsis due to decubitus inflammation based on bone marrow aspiration and a
      blood culture. Although granulocyte colony stimulating factor, packed red blood
      cell transfusions, platelet transfusions, and antibiotics gradually improved the
      pancytopenia, the patient died of massive gastrointestinal tract bleeding.

PMID- 16595998
TI  - Immunosuppressive treatment for mixed connective tissue disease may facilitate
      the development of adult T cell leukemia/lymphoma in a HTLVI carrier.
AB  - A 66-year-old woman who was positive for human T-lymphotropic virus type I (HTLV
      I) antibody developed mixed connective tissue disease (MCTD) with interstitial
      pneumonia, and was successfully treated with corticosteroid. One year later,
      under maintenance treatment of prednisolone (PSL), she contracted acute type
      adult Tcell leukemia/lymphoma (ATLL) without flaring of MCTD. MCTD is considered
      to be as one of the HTL-V-I-related inflammatory diseases, however the
      development of ATLL during the treatment of HTL-V-I-related MCTD has not been
      well studied. Here, we review the literature and raise the issue of the mutual
      interactions between MCTD-causative anti-HTLV-I immune response and anti-ATLL
      immune response.

PMID- 16596000
TI  - A primary follicular lymphoma of the duodenum treated successfully with radiation
      therapy.
AB  - A 48-year-old man was admitted to our hospital because of repeated episodes of
      epigastralgia. Endoscopy showed multiple whitish granules extending from the 2nd
      to 3rd portion of the duodenum. Biopsy specimens showed well circumscribed
      follicles with a monotonous population of predominantly small cleaved cells that
      were positive for CD20, CD10 and BCL2, but negative for CD5. A full staging study
      showed no abnormalities. The tumor was finally diagnosed according to the WHO
      classification as a stage I follicular lymphoma (FL), grade 1, of the duodenum
      and subsequently received irradiation to the involved area. After 3 years of
      followup, he is still in complete remission. Because FL arising in the duodenum
      has recently reported with increasing frequency, patients with multiple granules
      in the duodenum should be examined carefully.

PMID- 16596001
TI  - Infliximab is effective for Takayasu arteritis refractory to glucocorticoid and
      methotrexate.
AB  - We have experienced a Takayasu arteritis (TA) patient, successfully treated with
      infliximab, who did not respond well to conventional therapy with glucocosteroid
      and methotrexate. Takayasu arteritis had developed in a 24-year-old woman (March
      2003) who had been treated with glucocorticoid including methylprednisolone pulse
      therapy and methotrexate; however, she relapsed during the tapering of the dosage
      of oral prednisolone. Nineteen months after the first administration of
      glucocorticoid, 3 mg/kg of infliximab was introduced to the patient. The
      therapeutic efficacy of infliximab was markedly demonstrated; the patient's C
      reactive protein (CRP) value returned to almost normal range with subsequent
      tapering of the dosage of oral prednisolone in the absence of further relapse.
      This is the first case presentation of TA in Japan successfully treated with
      infliximab.

PMID- 16596002
TI  - Successful vancomycin desensitization with a combination of rapid and slow
      infusion methods.
AB  - Vancomycin, an antibiotic to which methicillin-resistant Staphylococcus aureus
      (MRSA) is sensitive, frequently induces hypersensitivity reactions. Lowering the
      vancomycin infusion rate and/or premedicating with antihistamine effectively
      reduce hypersensitivity in most cases. However, vancomycin desensitization is
      sometimes the only way to ensure safe use. Two types of desensitization protocols
      have been reported, and these utilize different infusion intervals; rapid
      desensitization and slow desensitization. We herein report a case of vancomycin
      hypersensitivity with methicillin-resistant Staphylococcus aureus infection. A
      combination of the two desensitization protocols, rapid desensitization followed
      by slow desensitization, effectively inhibited the hypersensitivity reaction
      during vancomycin infusion, and methicillin-resistant Staphylococcus aureus was
      successfully eradicated.

PMID- 16596004
TI  - Colestimide reduces blood polychlorinated biphenyl (PCB) levels.

PMID- 16596003
TI  - Q fever with clinical features resembling systemic lupus erythematosus.
AB  - A 23-year-old woman with prolonged fever, rash, and pericarditis associated with
      high titers of antinuclear, anti-Sm, and anti-RNP antibodies was suspected of
      having systemic lupus erythematosus (SLE). However, we also considered infectious
      diseases, particularly Q fever, as the C-reactive protein level was elevated and
      the patient reported contact with zoo animals around two weeks before the onset.
      The condition responded rapidly to administration of minocycline; symptoms
      resolved without using steroids. Thereafter, no recurrence of the illness was
      observed. Titer of Coxiella burnetii antibody was high and the illness was
      accordingly diagnosed as acute Q fever rather than SLE.

PMID- 16596005
TI  - Portomesenteric venous gas and pneumatosis intestinalis.

PMID- 16596006
TI  - Sigmoid volvulus showing "a whirl sign" on CT.

PMID- 16596007
TI  - Osborn wave in accidental hypothermia.

PMID- 16596008
TI  - Psammoma bodies in lung cancer.

PMID- 16596009
TI  - Bence Jones myeloma cells with crystalline inclusions.

PMID- 16596010
TI  - Prominent pleural effusion possibly due to imatinib mesylate in adult
      Philadelphia chromosome-positive acute lymphoblastic leukemia.

PMID- 16596011
TI  - Bone marrow metastasis of malignant melanoma.

PMID- 16596012
TI  - Rapidly reversible neurological manifestations in a case of neuro-Behcet disease.

PMID- 16596013
TI  - Venous angioma with epilepsy.

PMID- 16596014
TI  - High iron stores and risk of ischemic stroke in persons with metabolic syndrome.

PMID- 16596015
TI  - The development of new communication technologies and patient-doctor interaction.

PMID- 16596016
TI  - [Neurotrophic factor responsiveness of adrenal medullary cell line tsAM5D
      immortalized with temperature-sensitive SV40 T-antigen].
AB  - We established adrenal medullary cell lines from transgenic mice expressing an
      oncogene, the temperature-sensitive simian virus 40 large T-antigen, under the
      control of the tyrosine hydroxylase promoter. A clonal cell line, named tsAM5D,
      conditionally grew at a permissive temperature of 33 degrees C and exhibited the
      dopaminergic chromaffin cell phenotype as exemplified by the expression pattern
      of mRNA for catecholamine synthesizing-enzymes and secretory vesicle-associated
      proteins. tsAM5D cells proliferated at the permissive temperature in response to
      glial cell line-derived neurotrophic factor (GDNF), basic fibroblast growth
      factor (bFGF) and ciliary neurotrophic factor (CNTF). At a nonpermissive
      temperature of 39 degrees C, GDNF and CNTF acted synergistically to differentiate
      tsAM5D cells into neuron-like cells. In addition, tsAM5D cells caused to
      differentiate by GDNF plus CNTF at 39 degrees C became dependent solely on nerve
      growth factor for their survival and showed markedly enhanced neurite outgrowth.
      In the presence of GDNF plus CNTF, the morphological change induced by the
      temperature shift was associated with up-regulated expression of neuronal marker
      genes including microtubule-associated protein 2, neuron-specific enolase,
      neurofilament, and growth-associated protein-43, indicating that the cells
      underwent neuronal differentiation. Thus, we demonstrated that tsAM5D cells could
      proliferate at permissive 33 degrees C, and also had the capacity to terminally
      differentiate into neuron-like cells in response to GDNF plus CNTF when the
      oncogene was inactivated by shifting the temperature to nonpermissive 39 degrees
      C. These results suggest that tsAM5D cells should be a good tool to allow a
      detailed study of mechanisms regulating neuronal differentiation.

PMID- 16596017
TI  - [Analysis by structural equation modeling of the questionnaire about the risk and
      its preventive measures in a pharmacy].
AB  - Pharmacists are now facing a problem of developing measures for dispensing
      mistakes, because there recently is increasing social awareness on medical
      accidents and a tendency to increase medical accidents in pharmacies due to
      popularizing separation of dispensing and prescribing functions. In this study,
      questionnaire survey was conducted to investigate pharmacist's views on human
      error measures and the relationship between mistakes and the preventive measures.
      To clarify relationship between human error measures and preventive measures for
      avoiding mistakes, questionnaire result was analyzed based on structural equation
      modeling (SEM). Questionnaire survey was sent to community pharmacies in
      Hokkaido. The result was analyzed by SEM. The recovery rate of the questionnaire
      was 71.0%. Human error measures were classified into "The measures against
      deficient knowledge and insufficient experiences". "Attention problem measures"
      and "The measures against a cognitive error". While attention problem was
      strongly related to the cognitive error, there was no relationship between
      "Attention problem measures" and "The measures against a cognitive error".
      Moreover, it were clarified that to develop human error measures for deficient
      knowledge and insufficient experiences was effective for the preventive against
      the mismatch of the cognitive mechanism and the intentional mistake and for
      bridging the gap between knowledge and experiences. This study showed that SEM
      was effective for adopting efficient preventive measures for medical accident and
      analyzing risk management in pharmacies. Applying these results to the medical
      accident preventive measures contribute to improvement of the risk management.

PMID- 16596018
TI  - Method for detecting health injury from prescriptions at a pharmacy.
AB  - A method is proposed to detect the abnormal situations of people's health in case
      of the unexpected outbreak of a disease by monitoring the daily variations in the
      prescriptions at a pharmacy. The abnormal situations are defined as the
      situations which are not included in the majority (99.9%) of the normal
      situations. An epidemic probably caused by infectious micro-organisms in a
      terrorist attack is taken as an example. The drugs for the typical symptoms are
      monitored: influenza anti-viral agent and common cold drug. This paper
      demonstrates that the border between the normal and abnormal situations
      corresponds to the detection limit which is a fundamental concept in analytical
      chemistry.

PMID- 16596019
TI  - Usefulness of the final filter of the IV infusion set in intravenous
      administration of drugs--contamination of injection preparations by insoluble
      microparticles and its causes.
AB  - The purpose of this study is to clarify the presence of so much insoluble
      microparticles in the injections and to confirm the usefulness of the final
      filter for its removal. The test drugs used were Doyle 1 g vial, Cefotax 1 g
      vial, Minomycin 100 mg vial, Omegacin 0.3 g vial, Maxipime 1 g vial, Rocephin 1 g
      vial, Isovorin 25 mg vial, Diamox 500 mg vial and Fungizone 50 mg vial. 1) An
      appropriate volume of physiological saline was poured into the test drug vial
      from the 500 ml physiological saline bag. 2) The dissolution of the preparation
      was checked. 3) That test drug solution was returned into the same 500 ml
      physiological saline bag. 4) 5 ml of test drug solution was extracted from the
      inside of the 500 ml physiological saline bag. 5) The number of insoluble
      microparticles in the each test drug solution at pre- and post-filtrations were
      counted by using a particle counter for the solution. Two results were shown as
      follows (microparticle size: 5 microm or greater), (a) Doyle 1 g (ASPC): The
      number of insoluble microparticles in pre- and post-filtrations of a Doyle 1 g
      vial were 250 +/- 45 and 0/5 ml, respectively (microparticle size: < or =5 microm
      1662/5 ml, 5-10 microm: 238/5 ml, >10 microm: 11/5 ml). (b) Diamox 500 mg
      (acetazolamide): The number of insoluble microparticles in pre- and post
      filtrations of Diamox were 158 +/- 53 and 0.3 +/- 0.47/5 ml, respectively
      (microparticle size: < or =5 microm 4030/5 ml, 5-10 microm: 144/5 ml, >10 microm:
      14/5 ml). The presence of great numbers of insoluble microparticles in several
      injection preparations was clarified. Although the all test drugs used cleared
      the criteria of the number of insoluble microparticles of the Japanese
      Pharmacopoeia, it was suggested to be not suitable that great numbers of
      insoluble microparticles were administrated in the body fluid of patients,
      because a possibility to occlude capillaries and/or to injure the tissues by them
      was been thought. But we could remove them nearly completely by passing the
      solutions of drugs through an infusion filter. Otherwise, in this examination, we
      found that so much insoluble microparticles derived from the disposable syringe
      (10 ml) were used for dissolving freeze-dried preparations routinely
      (microparticle size: < or =5 microm 329/5 ml, 5-10 microm: 125/5 ml, >10 microm:
      39/5 ml). These results suggest that incorporation of a final filter in the IV
      line is extremely necessary not only for the prevention of bacterial infections,
      but also for elimination of insoluble microparticles.

PMID- 16596020
TI  - [Effect of orally administered chondrosine on uptake of 35S sulfate into rat
      cartilage].
AB  - Chondroitin sulfate is widely distributed in animal tissues and possibly plays an
      important role in different types of metabolic reactions as well as protecting
      joints, the internal wall of blood vessels, skin, bone, etc. In cartilage,
      glycosaminoglycans have a protective function; in particular, chondroitin sulfate
      stabilizes fibrous and cellular elements of the connective tissue and, at the
      same time, lubricates and protects the membranes in joints. Recently, chondroitin
      sulfate has been used as a nutraceutical for the treatment of joint diseases such
      as osteoarthritis, although acidic and large molecules such as chondroitin
      sulfate might not be able to be absorbed through digestive apparatus such as the
      intestine. In this study, we investigated the effects of orally administered
      chondrosine derived from shark chondroitin sulfate on the uptake of inorganic
      (35)S sulfate into rat cartilage and found that chondrosine stimulates the
      incorporation of (35)S sulfate into cartilage compared with intact chondroitin
      sulfate.

PMID- 16596021
TI  - Effects of essential oil extracted from Nigella sativa (L.) seeds and its main
      components on human neutrophil elastase activity.
AB  - The effects of essential oil extracted from Nigella sativa (L.) seeds and its
      main components on human neutrophil elastase (HNE) activity were investigated.
      Essential oil was extracted from N. sativa (L.) seeds using hydrodistillation.
      The yield was equal to 0.4%. Inhibition of HNE activity by essential oil was
      found to be dose dependent. The highest inhibitory concentration (HIC) of
      essential oil which caused total inhibition of HNE activity was 5.8 mg/ml.
      Microassays carried out to evaluate the inhibitory effect of major components of
      essential oil on HNE activity revealed that carvacrol (5-isopropyl-2
      methylphenol) showed marked HNE inhibitory activity with a very low IC(50) value
      (12 microM). Based on these results, the inhibitory effects of essential oil on
      HNE activity are due to the presence of bioactive molecules, mainly carvacrol
      this compound is an inhibitor of HNE and could be considered as a natural
      antielastase agent and possible candidate for phytotherapy in the treatment of
      injuries that appear in some pathologic cases such as chronic obstructive
      pulmonary disease and emphysema.

PMID- 16596022
TI  - Aqueous solubility of liquid monoterpenes at 293 K and relationship with
      calculated log P value.
AB  - Aqueous solubility is often a limiting factor in any concentration-dependent
      process and n-octanol/water partition coefficient, usually expressed as log P, is
      equilibrium between surrogate of nonaqueous biophases and water phase. The
      aqueous solubility of seven liquid monoterpenes: (+/-)-beta-citronellol, (+/-)
      linalool, linalyl acetate, (-)-alpha-pinene, (-)-beta-pinene, eucalyptol and
      terpinen-4-ol were experimentally determined at 293 K. The obtained aqueous
      solubility data correlate well with log P values calculated by ACD/Log P
      software.

PMID- 16596023
TI  - Method for estimating the order of influenza infection between adults and
      children.
AB  - This paper puts forward a method for determining the infection order of influenza
      between adults and children from the daily variations in the amount of influenza
      anti-viral agents treated at a pharmacy. The time series of Tamiflu Capsule for
      adults and Tamiflu Dry Syrup for children are compared by means of the cross
      correlation function. The results from pharmacies located in Tokyo and Kanagawa
      show that the influenza infection period of adults is earlier than that of
      children, indicating the infection order: first adults and second children.
      However, a pharmacy in Saitama yields no clear result.

PMID- 16596024
TI  - Evaluation of binders in the preparation of medicinal carbon tablets by wet
      granule compression.
AB  - Medicinal carbon (MC) tablets were prepared to obtain an oral dosage form that
      can be easily taken. The MC tablets were made by the wet granule compression
      method, in which hydroxypropyl cellulose (HPC), carboxymethyl cellulose sodium
      (CMC-Na) and maltitol (MT) were applied as binders. Brilliant Blue FCF (BB) was
      used as a model drug. The binders were evaluated in terms of formability of the
      granules and tablets, their strength, disintegration of the tablets, and their
      effect on the adsorption potential of MC. HPC and CMC-Na gave the strong granules
      at a fairly low concentration, but more MT was needed to obtain the strong
      granules. The tablets could be formed only when using MT at 120% (w/w) of the MC
      amount. The tablet displayed good hardness and rapid disintegration. The
      adsorption potential was not affected by CMC-Na, and slightly prevented by MT.
      However, the adsorption ability of MC was lowered more with the increase in HPC.
      The granules and tablets exhibited similar adsorption potentials, which were a
      little lower than that of MC suspended in MT aqueous solution. Similar adsorption
      characteristics were also observed in a real drug, acetaminophen. It is suggested
      that the MC tablets prepared by the wet granule compression using MT as a binder
      should be useful as a compact dosage form of MC.

PMID- 16596025
TI  - Are beta blockers passe for the treatment of hypertension?

PMID- 16596026
TI  - An effectiveness study comparing algorithm-based antihypertensive therapy with
      previous treatments using conventional and ambulatory blood pressure
      measurements.
AB  - Effectiveness trials in hypertension enable the efficacy and safety of new drugs
      to be compared with previous therapy. Since these open-label trials could
      inadvertently be influenced by observer bias, this study has used ambulatory
      blood pressure monitoring (ABPM) to provide a rigorous blinded end point to
      validate the study conclusions. The study was performed in 675 patients with
      stage 1 or 2 hypertension despite receiving single-agent or fixed-dose
      combination therapy. After baseline ABPM, the previous treatment was replaced by
      telmisartan 40 mg daily; if control (office blood pressure <140/90 mm Hg) was not
      achieved in 2 weeks, the dose was increased to 80 mg, and if necessary, a fixed
      combination with hydrochlorothiazide 12.5 mg was used after a further 4 weeks.
      ABPM was repeated after 4 weeks on final therapy. Overall, 50% of patients
      finished on monotherapy and 50% on combination therapy. By office measurements,
      there was a decrease (mean +/- SEM) of 16.8+/-0.5/10.3+/-0.3 mm Hg (p<0.001) when
      telmisartan-based treatment replaced previous treatment; by ABPM, the decrease
      was 8.2+/-0.4/5.0+/-0.2 mm Hg (p<0.001). The decreases were significant for
      comparisons with each of the prior drug classes. A treatment algorithm based on
      the angiotensin receptor blocker, telmisartan, was confirmed by the blinded end
      point of ABPM as an efficacious alternative to other antihypertensive regimens in
      clinical practice.

PMID- 16596027
TI  - The prevalence of primary aldosteronism in diabetic patients.
AB  - Increased plasma aldosterone concentrations (PACs) are associated with higher
      cardiovascular risk and target organ damage (TOD). Hyperglycemia can potentiate
      the cellular effects of aldosterone, and the prevalence of diabetes in primary
      aldosteronism (PA) is 7%-59%. The prevalence of PA in hypertensive individuals is
      estimated to be 10%-14%. This study of 61 hypertensive diabetic patients not
      taking spironolactone and with serum creatinine values <2.5 mg/dL sought to
      establish the prevalence of PA in hypertensive diabetics and compare the
      prevalence of PA in patients with TOD with those patients without TOD. PA was
      suspected if PACs were >15 ng/dL and plasma renin activity was <1 ng/dL/h (ratio
      >30). Although 14 patients had suppressed renin with PACs >8 ng/dL (including two
      with PACs >11 ng/dL), none met our criteria for PA. There was no correlation
      between PAC and TOD. This study indicates that routine screening for PA in
      hypertensive diabetic patients is not justified and that PAC does not correlate
      with TOD. Further study is needed.

PMID- 16596028
TI  - The effect of extended-release metoprolol succinate on C-reactive protein levels
      in persons with hypertension.
AB  - The objective of this study was to determine whether 3 months of treatment with
      extended-release metoprolol succinate would reduce C-reactive protein (CRP)
      levels. Seventy-five patients aged 30-65 years with uncontrolled hypertension
      were treated with extended-release metoprolol at 25-50 mg, titrated up to 100-200
      mg daily. CRP was evaluated at baseline and at 1 and 3 months. In the 61
      hypertensive patients who completed the study, CRP decreased from 6.2+/-7.5 mg/L
      at baseline to 5.4+/-7.0 mg/L (p=0.03) at 1 month and showed no further change at
      3 months (5.6+/-6.5 mg/L; p=0.13). The 13 patients who received 200 mg of
      extended-release metoprolol had a 32% decline in CRP from 7.0+/-9.0 mg/L to 4.8+/
      6.6 mg/L (-2.2 mg/L) (p=0.005) over the 3-month period, whereas lower doses did
      not reduce CRP (p>0.05). Age, race, sex, and change in blood pressure were not
      related to the reduction in CRP in multivariate analysis. If CRP evolves into a
      confirmed modifiable risk factor, a beta blocker such as metoprolol may be a
      useful addition to pharmacotherapy options.

PMID- 16596030
TI  - Sexual dysfunction in essential hypertension: myth or reality?
AB  - Erectile dysfunction is currently considered a condition with high prevalence in
      the general population, exerting a major impact on patients' and their sexual
      partners' quality of life. Available data indicate that hypertension represents a
      risk factor for erectile dysfunction, which is more frequent in hypertensive
      compared with normotensive subjects. The pathophysiologic basis of erectile
      dysfunction in hypertension is under thorough investigation, and several
      mechanisms have been proposed. Erectile dysfunction has also been related to
      cardiovascular risk factors and might be used as a marker of cardiovascular
      disease in the future. Although male sexuality has been studied rather
      extensively, female sexual dysfunction in hypertension is underexplored. Recently
      published hypertension guidelines either ignore or superficially address sexual
      dysfunction, underlining the need for more attention and better education of
      health care professionals on this issue.

PMID- 16596029
TI  - The pleiotropic effects of angiotensin receptor blockers.
AB  - The angiotensin receptor blockers (ARBs) are very effective and safe
      antihypertensive drugs. They exert their antihypertensive effect through blockage
      of the angiotensin II, type 1 receptor and quite possibly through stimulation by
      angiotensin II of the unoccupied type 2 receptor. Besides hypertension, the ARBs
      have been found recently to be of value in the treatment of heart failure and
      diabetic nephropathy. In addition, ARBs have emerged lately as being very
      effective and perhaps superior to other antihypertensive drugs in the prevention
      of de novo or recurrent strokes. Other actions that may account for their stroke
      protective effects include their antiatherogenic, antidiabetic, antiplatelet
      aggregating, hypouricemic, and atrial antifibrillatory actions. All these actions
      make the ARBs a true pleiotropic class of drugs. Each of the foregoing effects
      will be discussed briefly in this concise review.

PMID- 16596031
TI  - Hypertensive emergencies.
AB  - Following a hypertension symposium in Rochester, NY, in October 2005, a
      roundtable was convened to discuss hypertensive emergencies. Dr. Marvin Moser,
      Clinical Professor of Medicine at the Yale University School of Medicine, New
      Haven, CT, moderated the session, which included Dr. Joseph L. Izzo, Jr.,
      Professor of Medicine at the State University of New York at Buffalo, Buffalo,
      NY, and Dr. John Bisognano, Associate Professor of Medicine at the University of
      Rochester School of Medicine, Rochester, NY.

PMID- 16596032
TI  - New definitions of hypertension.

PMID- 16596033
TI  - Edward D. Freis--a true pioneer.

PMID- 16596034
TI  - What's in a pulse? Part 2.

PMID- 16596035
TI  - Type B aortic dissection: management in a young man with neurologic sequelae.

PMID- 16596036
TI  - Antihypertensive pharmacobezoar.
AB  - Most antihypertensive drugs have known side effects that are elicited by the
      careful clinician taking care of hypertensive patients. However, many
      antihypertensive medications utilize drug delivery systems that prolong the
      duration of blood pressure reduction. The gastrointestinal therapeutic system
      that is used with nifedipine, isradipine, and verapamil has a unique side effect.
      Obstruction may occur at the site of a previous surgical repair (pyloric stenosis
      or gastroplasty) or stenosis of the esophagus, small intestine, or colon. The
      same delivery system is used with methylphenidate, oxybutynin, glipizide, and
      doxazosin. Although this complication is rare, physicians who prescribe and care
      for hypertensive patients should recognize this potential problem.

PMID- 16596037
TI  - Analysis of recent papers in hypertension.

PMID- 16596039
TI  - Myocardial perfusion as assessed by positron emission tomography during long-term
      mechanical circulatory support.
AB  - Although mechanical circulatory support (MCS) can improve myocardial function in
      patients with advanced heart failure, its effects on relative myocardial
      perfusion are unclear. Using positron emission tomographic imaging techniques,
      the authors assessed relative myocardial perfusion in patients with ischemic or
      idiopathic cardiomyopathy who were receiving chronic MCS with a left ventricular
      assist device (pulsatile HeartMate [n = 2] [Thoratec Corporation, Pleasanton, CA]
      or nonpulsatile Jarvik 2000 [n = 4] [Jarvik Heart, Inc., New York, NY]). Relative
      myocardial perfusion was compared at lower and higher levels of MCS (50 vs. 100 -
      110 ejections/min for the HeartMate and 8000 vs. 12,000 rpm for the Jarvik 2000).
      The size and severity of perfusion defects at rest and after dipyridamole stress
      were measured objectively and subjectively by computer algorithms and visual
      inspection, respectively. Relative myocardial perfusion increased > 5% from
      baseline in only one of six patients when MCS was increased. No change in
      relative myocardial perfusion of > 5% was seen in any of the other five patients,
      even after subsequent dipyridamole stress positron emission tomographic imaging.
      These pilot study findings suggest that the decreased metabolic requirements
      induced by ventricular unloading correspondingly decreased blood flow
      requirements to physiologically inactive myocardium.

PMID- 16596040
TI  - The effect of anemia on mortality in indigent patients with mild-to-moderate
      chronic heart failure.
AB  - Anemia has been described as an independent predictor of death in patients with
      chronic heart failure. Little is known, however, about the significance of anemia
      in heart failure patients with severely depressed socioeconomic backgrounds who
      receive comprehensive care in a heart failure management program. The impact of
      anemia on mortality was investigated in 410 indigent chronic heart failure
      patients, the majority of whom were in New York Heart Association functional
      class I-III and were treated with angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers and beta blockers at maximally tolerated doses.
      Anemia was present in 28% of patients. In an adjusted Cox analysis, anemia was
      strongly associated with mortality, but only in men: hazard ratio, 2.54; 95%
      confidence interval, 1.31-4.93; p = 0.006. The investigators conclude that anemia
      in this population is common and that, for men, the relative risk increase
      associated with anemia is high.

PMID- 16596041
TI  - Brain natriuretic peptide levels and left ventricular functional recovery in a
      chronic heart failure population.
AB  - Due to the poor correlation between symptoms and left ventricular (LV) ejection
      fraction in a chronic heart failure (HF) population, the ability to identify
      patients who demonstrate LV functional recovery poses a dilemma for the
      clinician. Serial echocardiograms are not practical in a large outpatient HF
      population. Plasma brain natriuretic peptide (BNP) levels have a high predictive
      value for excluding patients with ventricular dysfunction and therefore could
      serve as a marker for identifying patients who demonstrate improved LV function.
      To evaluate this point, the researchers obtained baseline BNP levels in 380
      chronic systolic HF patients seen in an outpatient HF clinic. Each patient
      already had a baseline echocardiogram performed before or on entry into the
      clinic. Fifty patients were identified in this group as having normal BNP levels
      (< or = 100 pg/mL). Echocardiograms were then repeated in this group and compared
      with initial echocardiographic data obtained from a retrospective chart review.
      The results showed that the mean LV ejection fraction for the group was increased
      (p < 0.001), mean LV internal dimension was decreased (p < 0.001), and the number
      of patients with an ejection fraction > 50% increased from zero to 20 (p <
      0.001). Thus, normal BNP levels can correlate with LV recovery and could
      potentially offer a cost-effective method of assessing changes in LV function in
      patients with chronic HF.

PMID- 16596042
TI  - Obese patients have lower B-type and atrial natriuretic peptide levels compared
      with nonobese.
AB  - Obesity is a risk factor for the development of heart failure, but the causal
      mechanism remains unclear. Impaired production or enhanced clearance of
      natriuretic peptides, which regulate sodium balance and sympathetic activation,
      may play an important role. The authors investigated the relationship of plasma B
      type natriuretic peptide and atrial natriuretic peptide levels to body mass index
      in 100 patients referred for left heart catheterization. Hemodynamic and
      echocardiographic data were obtained for all study participants. Atrial
      natriuretic peptide and B-type natriuretic peptide levels were compared in obese
      (body mass index > or = 30 kg/m2) and nonobese (body mass index < 30 kg/m2)
      subjects. Multivariate regression analyses were performed, adjusting for clinical
      and hemodynamic covariates. Obese patients had significantly lower B-type
      natriuretic peptide (p = 0.03) and atrial natriuretic peptide (p = 0.04) levels
      compared with nonobese. Multivariate analysis revealed lower B-type natriuretic
      peptide (p = 0.095) and atrial natriuretic peptide (p = 0.007) levels in obese
      patients while controlling for age, sex, left ventricular end-diastolic pressure,
      and left ventricular ejection fraction. Low levels of circulating natriuretic
      peptides are thus associated with obesity and may contribute to the development
      of heart failure.

PMID- 16596043
TI  - Immune modulation therapy in heart failure.
AB  - Several lines of evidence suggest that inflammation plays a pathogenic role in
      the development and progression of congestive heart failure, influencing heart
      contractility and hypertrophy, promoting apoptosis, and contributing to the
      myocardial remodeling process. As the prevalence of heart failure continues to
      increase, novel therapeutic strategies are employed to decrease the burden of
      this disease. Although multiple studies have suggested a potential for
      immunomodulatory therapy in heart failure patients, the precise role of this
      targeted approach still remains to be determined. Further research is needed to
      identify the key factors in the immunopathogenesis of heart failure, identify the
      patients who are most likely to respond, and develop management strategies that
      result in consistent benefit leading to decreased morbidity and mortality in the
      heart failure patient population.

PMID- 16596044
TI  - Overview of B-type natriuretic peptide as a blood test. Roundtable discussion.
AB  - A roundtable discussion was convened in December 2005 to discuss current and
      future applications of blood B-type natriuretic peptide testing in the diagnosis
      and treatment of cardiovascular disease. Dr. Peter McCullough, consulting
      cardiologist and Chief of the Division of Preventive Medicine at William Beaumont
      Hospital in Royal Oak, MI, chaired the discussion. Dr. Christian Mueller,
      consultant cardiologist and active researcher in the area of cardiac natriuretic
      peptides at the Department of Internal Medicine, University Hospital, Basel,
      Switzerland; and Dr. Clyde Yancy, Associate Dean for Medical Affairs at the
      University of Texas Southwestern Medical Center, Dallas, TX, participated in the
      discussion.

PMID- 16596045
TI  - The cost effectiveness of B-Type natriuretic peptide measurement in the primary
      care setting-a UK perspective.

PMID- 16596046
TI  - Cost effectiveness of natriuretic peptide measurement in the primary care
      setting: have we found the gatekeeper for the evaluation of dyspneic outpatients?

PMID- 16596047
TI  - BiDil (isosorbide dinitrate and hydralazine hydrochloride).

PMID- 16596048
TI  - History vignettes in heart failure.

PMID- 16596049
TI  - Pacemaker-induced mitral regurgitation as a cause of refractory congestive heart
      failure during pacing therapy in a patient with hypertrophic obstructive
      cardiomyopathy.
AB  - This report describes a woman with hypertrophic obstructive cardiomyopathy in
      whom initial hemodynamic improvement by dual chamber (DDD) pacing with short
      atrioventricular delay was excellent, but severe mitral regurgitation developed
      during the subsequent follow-up period, resulting in refractory congestive heart
      failure. There were two possible explanations for the origin of the complicating
      mitral regurgitation in this patient: pacing-induced semiclosure of the mitral
      valve, or left ventricular asynchrony caused by right ventricular pacing. Heart
      failure in patients with hypertrophic obstructive cardiomyopathy who undergo
      placement of a DDD pacemaker to improve not only mitral regurgitation but also
      heart failure symptoms can be associated with systolic mitral regurgitation as
      the cause of failure in DDD pacing therapy.

PMID- 16596051
TI  - [Management of asymptomatic primary hyperparathyroidism: French Society of
      Endocrinology expert consensus].

PMID- 16596052
TI  - [Diffuse uptake of brown fat on computed-tomography coupled positron emission
      tomoscintigraphy (PET-CT) for the exploration of extra-adrenal pheochromocytoma].
AB  - We report an observation of strong bilateral uptake on a PET-CT scan compatible
      with activation of brown adipose tissue in a patient with extra-adrenal
      pheochromocytoma. A 42-year-old man was hospitalized for hypersudation together
      with weight loss and palpitations. Heart rate was 120 bpm and fasting blood
      glucose 1.36 g/l. Endocrine explorations revealed elevated serum chromogranine
      which reached 517 ng/ml (19-38). The norepinephrine level reached 49.7 nmol/l
      (<4.00) and urinary norepinephrine and normetanephrine levels reached 13977
      nmol/24h (<414) and 32 micromol/24h (0.4-2.5) respectively. The thoraco-abdominal
      and pelvic scan showed a 6 cm diameter paraaortic hypervascularized mass with an
      infiltrative lesion of both perirenal area and mediastinal tissue without
      adenopathies. The abdominal MRI revealed the mass with a low intensity signal in
      T1 and a slight high intensity signal in T2. MIBG and octreoscan scintigraphies
      were negative. 18F-DG PET showed intensed uptake in the tumor mass together with
      intense, diffuse and bilateral uptake above and below the diaphragm. The mass was
      resected. Histological examination of the surgical specimen confirmed the
      diagnosis of extra-adrenal pheochromocytoma with an index of 13% cellular
      proliferation without cell atypia. There was a hypervascularization with small
      islets of brown adipose tissue in the perirenal fat. Both plasmatic and urinary
      catecholamines decreased to the normal range after the operation and PET-scan
      normalized. Bilateral spread of the radiotracer uptake was probably due to brown
      adipose tissue activation by excessive sympathetic stimulation induced by
      catecholamines released by the tumor.

PMID- 16596053
TI  - [Characterization of RET proto-oncogene C634Y mutation in a Moroccan family with
      multiple endocrine neoplasia type 2A].
AB  - Medullary thyroid carcinoma (MTC) is a rare cancer which originates from the
      calcitonin producing "C" cells of thyroid gland. It presents in as isolated form
      or as part of the multiple endocrine neoplasia type 2 (MEN 2). The familial form
      of MTC which frequency remains underestimated, account for 25 to 40% of all MTC
      presentations. All hereditary forms are transmitted in an autosomal dominant
      manner and are due to proto-oncogene RET germ line mutations. Although MCT is
      relatively rare, preclinical or prebiological diagnosis can be achieved with
      genetic screening with high specificity and sensitivity. Early diagnosis is
      crucial for disease prevention. In this study we identified the first RET
      mutation underlying NEM 2A in Morocco. The C634Y mutation was present in the
      heterozygous state in a Moroccan family with MEN 2A. Genetic screening showed
      that six asymptomatic members of this family were not C364Y carriers. This report
      should contribute to the development of genetic screening for NEM 2 and F-MTC in
      Morocco.

PMID- 16596054
TI  - [Evaluation of bone mineral density in hyperthyroid patients before and after
      medical therapy].
AB  - Osteoporosis is a common complication of hyperthyroidism, but it is not often
      evaluated. The aim of this study is to examine bone mineral density (BMD) (dual
      energy X-ray absorptiometry: DEXA) in lumbar spine (L1-L4), femoral neck (FN) and
      Ward's triangle (TW) in 45 hyperthyroid patients (group A: n 25 active
      hyperthyroidism, group B: n 20 controlled hyperthyroidism on medical therapy,
      after a mean of 7 months of euthyroidism), compared to control group (group C: n
      22). These 3 groups are adjusted by age, sex, menopausal status and BMI. In
      hyperthyroid patients (group A), as compared to the control group, we noticed a
      significant reduction of BMD (z score) in different sites, more markedly in the
      lumbar spine (p L1-L4: 0,005; p FN: 0,011; p TW: 0,019). In group A, no
      differences were found between BMD values after adjustment for Z score whatever
      the menopausal status (p L: 0.12; p FN: 0.33; p TW: 0.09) and degree
      ofhyperthyroidism (p L: 0.48; p FN: 0.41; p TW: 0.21). The degree of BMD in group
      B patients was different from that of patients in group A (p L: 0.37; p FN: 0.28;
      p TW: 0.31). and was significantly lower than in those of group C except for the
      TW (p L: 0.009; p CF: 0.038; p TW: 0.068). We conclude that it is important to
      consider that after reaching euthyroidism hyperthyroidism patients present a bone
      risk.

PMID- 16596055
TI  - Feminizing adreno-cortical carcinomas in male adults. A dire prognosis. Three
      cases in a series of 801 adrenalectomies and review of the literature.
AB  - We describe the clinical presentation, biochemical features, diagnostic criteria,
      clinical course and differential diagnosis in three cases of feminizing adreno
      cortical carcinoma (FACC) with a review of the literature. PATIENTS: From 1970
      throughout December 2003 among a series of 801 adrenalectomies, three had been
      performed for FACC. RESULTS: Age at presentation was 74, 63 and 23 years.
      Estradiol hypersecretion was observed in 3/3 patients, 17 OH progesterone was
      elevated in 2/3 patients and both of them had a diminution of testosterone, delta
      4 androstenedione was elevated in 1/3 patients. Imaging studies suggested
      malignancy in 3/3 patients by the presence of necrosis, heterogeneity,
      calcifications, size of the tumor and compression of adjacent organs. All
      patients were stage III at presentation and had a Weiss score >or=6. Size and
      weight of the tumors were 30, 20, 15cm and 3750, 480 and 275g respectively. All 3
      patients received mitotane and cortisone post-operatively and at follow up (7, 3
      and 2 years) all 3 died of the disease. CONCLUSIONS: Feminizing adreno-cortical
      carcinomas in adults are exceedingly rare (1-2% of adreno-cortical carcinomas).
      Tumors are huge and even after surgery for cure their prognosis is worse than for
      other varieties of adreno-cortical carcinomas either secreting or non secreting.
      Early diagnosis and treatment may improve overall prognosis.

PMID- 16596056
TI  - [High cord blood TSH in Morocco: iatrogenic hypothyroidism?].
AB  - A short prospective study was conducted to assess thyroid status in healthy full
      term newborns (n=90) of a large maternity of Marrakech (Morocco), as part of the
      validation of a national salt iodisation program. High TSH (>5mU/l) was detected
      in 89% of infants tested; urinary iodine excretion was measured in 35 of the
      mothers, and was found to be normal (100-200microg/l) or high
      (>200microg/l)(n=27) in all of them. Milk iodine concentration was measured in
      315 lactating women from the same area. Low values (<41microg/l) were found in
      60% of them. The common use of iodinated disinfectants during delivery could be
      responsible for the high urine iodine values of mothers; however iodine
      deficiency seems to remain a widespread problem in this population and justifies
      a large scale survey of iodine status.

PMID- 16596057
TI  - [Beta interferon and thyroid].
AB  - We report the case of a thyroiditis in a 44-year-old woman with relapsing
      remitting multiple sclerosis treated with interferon beta. Before treatment,
      thyroid function tests were normal and anti-thyroid (anti-thyroglobulin and anti
      thyroid peroxidase) antibodies were negative. After 18 months of treatment, the
      patient presented clinical features of thyroiditis. We noted a rise in TSH values
      and anti-thyroid antibodies were found positive. Treatment was not discontinued
      and further surveillance showed an improvement in clinical and biological
      features. We conclude that thyroid function should be monitored during INF beta
      treatment. Laboratory tests must be carried out before therapy. Clinical follow
      up is indicated before undertaking biological tests.

PMID- 16596058
TI  - [Calcium sensing receptor: physiology and pathology].
AB  - Calcium is a major ion in human metabolism and its level is highly controlled.
      This regulation is performed via the Calcium Sensing Receptor, a discovery which
      ten years ago led to the explanation of a number of clinical disorders. The
      syndromes caused by CaSR abnormalities are characterized by hypercalcemia or
      hypocalcemia, associated with inappropriate calciuria. An underlying genetic or
      auto-immune cause may be demonstrated. High blood calcium levels linked to
      mutations of the CaSR gene lead to familial hypocalciuric hypercalcemia and the
      neonatal and non neonatal forms with severe hypercalcemic. Hypocalcemia
      determined by mutations in the CaSR gene include autosomal dominant hypocalcemia
      and its sporadic form. Another clinical presentation similar to Bartter syndrome
      has been reported. Auto-antibodies directed against CaSRs, seen in auto-immune
      diseases, can lead to similar clinical presentations. Finally, CaSR polymorphisms
      modulate the range of blood calcium levels. With diagnosis of these diseases
      deleterious therapeutics can be avoided. The discovery of this receptor has led
      to new therapeutic prospects such as calcimimetics for hyperthyroidism.

PMID- 16596059
TI  - [Ramadan fasting in type 2 diabetes mellitus].
AB  - This study was designed to assess the effects of fasting during Ramadan on
      weight, blood pressure, metabolic control and plasma lipoproteins in diabetic
      patients. This study was conducted in December 2000 (Ramadan 1421) when the
      length of fasting was 12 hours a day. It included 38 type 2 diabetic patients (20
      males and 18 females). Mean patient age was 51.410.5 years and mean body mass
      index (BMI) 28.94.7kg/m2. Three patients were treated with diet and 35 with oral
      hypoglycemic agents. Clinical and biochemical parameters were evaluated during
      three periods: three weeks before Ramadan (T0), at the fourth week of Ramadan
      (T1) and three weeks after the end of Ramadan (T2). During the month of Ramadan,
      a decrease in weight (0.52kg) and no change in blood pressure were observed. No
      metabolic complication occurred in our patients. A significant effect of Ramadan
      fasting was observed on glycemic control and lipoprotein levels. In patients
      whose fructosamine level before Ramadan was higher than 340micromol/l, plasma
      fasting glucose and serum fructosamine increased during Ramadan (p<0.003) and
      returned to initial levels at the end of Ramadan T2; in these patients also, a
      decrease of HDL-cholesterol (p<0.01) associated with an increase of LDL
      cholesterol (p<0.003) were observed at T1 and disappeared at T2. But, in patients
      whose fructosamine level at T0 was lower than 340micromol/l, no effect on
      glycemic control and no significant effect on serum lipoprotein levels were found
      during Ramadan month. Ramadan fasting in type 2 diabetic patients seems to cause
      slight effects on glycemia and lipoprotein levels when previous metabolic control
      is quite good; but fasting induces more deterioration when previous control is
      poor.

PMID- 16596060
TI  - [Do circannual rhythm of cortisol and testosterone interfere with variations
      induced by other events?].
AB  - OBJECTIVE: Cortisol and testosterone are two hormones whose levels may vary in
      response to sports or occupational events. We wondered if the circannual rhythm
      of these hormones could have an influence on such responses or whether changes
      can always be ascribed to a single cause. METHOD: For cortisol, we conducted a
      cross-sectional study among 102 adult men (mean age 42 years) using saliva
      samples taken one half hour after awakening. The values were combined over three
      month periods corresponding to the four seasons. For testosterone, conclusions
      were drawn from data reported in the literature. RESULTS: The mean annual
      cortisol level was 14.36+/-0.44 nmol/l. There was no significant difference
      between average and peak values nor between maximal and minimal values. For
      testosterone, there have been a limited number of studies and it is unclear
      whether there is a seasonal change. In any case, the amplitude of variations is
      weak (9.7% between peak and annual average), which is partly ascribable to
      individual and interindividual variability. CONCLUSION: We conclude that there is
      no seasonal (or circannual) rhythm in cortisol levels to a degree which could
      interfere with effects resulting from other events. For testosterone, the
      circannual rhythm may account for 10% of the variation.

PMID- 16596061
TI  - [Biphasic sarcomatoid carcinoma of the thyroid: an exceptional localization of a
      rare tumor].
AB  - Thyroid sarcomatoid carcinoma is a rare and aggressive neoplasm composed of a
      follicular carcinoma which is contiguous or admixed with a pleomorphic spindle
      cell component. We report the case of a thyroid tumor reputed to have a poor
      outcome, in a 62-year-old woman. The radical thyroidectomy specimen was totally
      invaded. Results of immunoperoxidase staining for thyroglobulin and epithelial
      markers were positive in the areas of follicular carcinoma and negative in the
      sarcomatous component. The patient died a few days later due to septic shock. The
      epithelial and mesenchymal components of thyroid carcinosarcoma were both part of
      the neoplastic parenchyma and evolved from a single common stem cell, in
      agreement with the hypothesis that the tumors are of monoclonal origin. The
      definition of this tumor as its histogenesis and prognostic are discussed.

PMID- 16596080
TI  - Asperger syndrome revisited.
AB  - Asperger syndrome (AS) is a disorder on the continuum of autistic spectrum
      disorders characterized by a lack of social reciprocity and empathy, and severe
      difficulties in social integration. Controversy remains as to what constitutes AS
      and whether it should be declared a separate disease or higher-functioning
      autism. This review discusses the contributions made by Hans Asperger and Leo
      Kanner in first delineating the condition, and examines the syndrome's incidence,
      prevalence, and etiologies. Recent studies using neuroimaging are described,
      along with current diagnostic and treatment options.

PMID- 16596081
TI  - Angioplasty and stenting to treat occlusive vascular disease.
AB  - The advent of effective percutaneous treatment of occlusive vascular lesions by
      angioplasty and stenting is one of the most important contributions to medical
      care early in the 21st century. Evaluation of angioplasty and stenting procedures
      is still in a very early phase. New types of stents and other technologies and
      devices are being continuously developed and there is a definite learning curve.
      The experience, training, and number of procedures clearly relate to outcomes,
      and many different specialists are still learning and so far have not had optimal
      experience. This review provides an overview of studies that have examined the
      efficacy of stenting in conjunction with balloon angioplasty for carotid
      atherosclerosis compared with endarterectomy. Also discussed are
      angioplasty/stenting of other neck arteries and intracranial arteries and the key
      issues surrounding percutaneous intervention, including patient selection
      criteria, clinical assessment of lesions most suitable for treatment, the use of
      distal protective devices and drug-eluting stents, and recommendations for
      physician selection.

PMID- 16596082
TI  - How useful is (123I) beta-CIT SPECT in the diagnosis of Parkinson's disease?
AB  - Because clinical features of parkinsonism can occur in other forms of
      parkinsonian syndromes in addition to Parkinson's disease, neuroimaging may have
      a role in determining true disease status. Iodine-123 ((123)I) (2beta
      carboxymethoxy-3beta-[4-iodophenyl] tropane) or ((123)I) beta-CIT is a recently
      developed diagnostic biomarker of Parkinson's disease that provides in vivo
      information about nigrostriatal degeneration. In clinical trials, beta-CIT single
      photon emission computed tomography (SPECT) has been shown to be a highly
      sensitive diagnostic tool in differentiating clinically probable Parkinson's
      disease from normal subjects and essential tremor patients. As a tool for
      differentiating Parkinson's disease from atypical parkinsonian syndromes,
      ((123)I) beta-CIT SPECT may have more limited use because of more extensive
      postsynaptic pathology in the latter. Differentiating among various parkinsonian
      syndromes may be improved by methodological refinements, a combined strategy of
      imaging presynaptic and postsynaptic sites, or by metabolic imaging.

PMID- 16596083
TI  - Multiple sclerosis: pathologic, clinical, and imaging updates.
AB  - Highlights of the 21st Congress of the European Committee for Treatment and
      Research in Multiple Sclerosis, September 28-October 1, 2005, Thessaloniki,
      Greece.

PMID- 16596084
TI  - A 73-year-old woman with an acute illness causing fever and cranial nerve
      abnormalities.

PMID- 16596085
TI  - Isolated painful third nerve palsy.
AB  - A 50-year-old woman presented with an acute painful complete third nerve palsy
      involving the pupil. Noninvasive imaging ruled out an aneurysmal compression of
      the third nerve, and brain magnetic resonance imaging demonstrated an intrinsic
      lesion of the third nerve. Work-up remained negative. All symptoms and signs
      resolved with steroids. In this case review, we briefly discuss the management of
      isolated third nerve palsies.

PMID- 16596093
TI  - Time at or near VO2max during continuous and intermittent running. A review with
      special reference to considerations for the optimisation of training protocols to
      elicit the longest time at or near VO2max.
AB  - Several authors have suggested that training at or near VO2max (i.e. > or = 95%
      VO2max) is the most effective training intensity to enhance VO2max and that for
      highly trained endurance athletes, training at or near VO2max may be necessary to
      increase it further. Consequently, there is an interest in characterising
      training protocols that allow the longest time at or near VO2max (T@VO2max).
      Intermittent running protocols have been found to be more effective than
      continuous protocols for increasing T@VO2max. Intermittent protocols can be
      manipulated by altering the warm-up intensity and timing, work and relief
      interval velocity and duration, amplitude, interval number per set, and the
      number of sets performed. To increase T@VO2max it is recommended that work
      interval intensity should generally range between 90% and 105% vVO2max and relief
      interval intensity between 50% vVO2max and the lactate threshold velocity. Work
      and relief interval durations should be between 15 and 30 seconds. The warm-up
      period prior to the intermittent protocol should be about 10 to 15 minutes in
      duration at 1 or 2 km x h(-1) below the lactate threshold velocity, with no gap
      between the warm-up and the intermittent protocol. When designing intermittent
      training protocols for the enhancement of VO2max, the simultaneous enhancement of
      other physiological performance determinants should also be considered. Further
      experimental research is required to identify the specific physiological
      responses and adaptations to various intermittent running protocols that are
      designed to elicit the longest time at or near VO2max, before recommendations can
      be given to competitive endurance runners.

PMID- 16596094
TI  - The ventilatory anaerobic threshold is related to, but is lower than, the
      critical power, but does not explain exercise tolerance at this workrate.
AB  - AIM: The aim of the present study was to investigate the relationships between
      critical power (CP), maximal aerobic power and the anaerobic threshold and
      whether exercise time to exhaustion and work at the CP can be used as an index in
      the determination of endurance. METHODS: An incremental maximal cycle exercise
      test was performed on 30 untrained males aged 18-22 years. Lactate analysis was
      carried out on capillary blood samples at every 2 minutes. From gas exchange
      parameters and heart rate and lactate values, ventilatory anaerobic thresholds,
      heart rate deflection point and the onset of blood lactate accumulation were
      calculated. CP was determined with linear work-time method using 3 loads. The
      subjects exercised until they could no longer maintain a cadence above 24 rpm at
      their CP and exercise time to exhaustion was determined. RESULTS: CP was lower
      than the power output corresponding to VO2max, higher than the power outputs
      corresponding to anaerobic threshold. CP was correlated with VO2max and anaerobic
      threshold. Exercise time to exhaustion and work at CP were not correlated with
      VO2max and anaerobic threshold. CONCLUSIONS: Because of the correlations of the
      CP with VO2max and anaerobic threshold and no correlation of exercise time to
      exhaustion and work at the CP with these parameters, we conclude that exercise
      time to exhaustion and work at the CP cannot be used as an index in the
      determination of endurance.

PMID- 16596095
TI  - EMG analysis of muscle load during simulation of characteristic postures in
      dinghy sailing.
AB  - AIM: The aim of this work was to establish the characteristic values of the
      particular electromyographic (EMG) indicators in the simulation of hiking in the
      laser-standard class in dinghy sailing. METHODS: Seven top-level competitors
      participated in the study (age: 21.1+/-2.5 years; height: 184.1+/-5.7 cm; weight:
      78.4+/-3.7 kp). The 4 muscle groups analyzed were those which, according to
      expertise are exposed to the most strain during training and competition in all
      classes of dinghy sailing, as well as in the Olympic laser standard class
      (extensors of the lower leg, abdominal, lumbar and tibial muscles). A portable
      surface EMG apparatus was used for the recording of EMG signals. Digitized EMG
      data were full-wave rectified and smoothed. Their mean values during
      characteristic hiking positions (sitting--S, upright hiking--UH, leaning
      backwards hiking--LBH) were compared by means of repeated ANOVA measures.
      RESULTS: ANOVA showed significant differences for the absolute EMG signal between
      analyzed positions for quadriceps muscles (UH vs S, p < or = 0.001; LBH vs UH, p
      < or = 0.01), abdominal m (UH vs S, p < or = 0.001; LBH vs UH, p < or = 0.001),
      tibial m (UH vs S, p < or = 0.01; LBH vs UH, p < or = 0.05) and lumbar m (LBH vs
      UH, p < or = 0.01). According to results, the muscles most loaded are the
      quadriceps muscle of the thigh, followed by the abdominal muscles. CONCLUSIONS:
      The findings of this study allow for a better biomechanical understanding of the
      character of the load distribution in body musculature in positions
      characteristic of the laser-standard class sailing, and these insights might be
      applicable to other classes of dinghy sailing.

PMID- 16596096
TI  - Bilateral isokinetic peak torque of quadriceps and hamstring muscles in
      professional soccer players with dominance on one or both two sides.
AB  - AIM: Dominance of one leg may cause asymmetry between the contralateral muscle
      groups and develop predisposition for injury to the leg with the weaker muscle
      strength. The purpose of this study was to examine the strength balance in the
      extensor and flexor muscle groups, as well as the hamstring to quadriceps (H/Q)
      ratios of both legs in professional soccer players with dominance on one or both
      legs. METHODS: Forty-two professional soccer players of the first Greek division
      participated in this study. Participants were divided into 3 groups according to
      their leg use during training sessions and matches. Fifteen players comprised the
      first group with dominance to the right leg, 12 players formed the second group
      with dominance to the left leg, and 15 players consisted the third group with
      dominance to both the right and left legs. Maximum voluntary concentric torque of
      the hamstring and quadriceps muscles of both legs was assessed using a Norm
      isokinetic dynamometer at angular velocities of 12 degrees, 60 degrees, 180
      degrees and 300 degrees/s. RESULTS: No significant differences in the strength
      balance found between the groups. The isokinetic variables comparing the right
      and left body side in each group, with dominance on one or both legs, did not
      differ. No differences were recorded in the H/Q between the right and left legs
      for any of the subject groups. CONCLUSIONS: There is no evidence of muscle
      imbalances in extensor and flexor muscle groups and H/Q ratios between the right
      and left legs in professional soccer players with dominance on one or both legs.
      The training sessions and matches appear to have imposed strength balance for the
      right and left body sides of professional soccer players.

PMID- 16596097
TI  - Physiological and technical aspects of ''6-a-side'' soccer drills.
AB  - AIM: The purposes of the present study were: 1) to evaluate heart rate and
      technical-tactical differences, if any, during ''6-a-side'' drills, played on 2
      pitch dimensions (30x40 m and 50x40 m) and duration (3 min and 8 min); 2) to
      assess the variability of data between repeated experimental sessions; 3) to
      evaluate training intensities from heart rate at lactate threshold. METHODS:
      Laboratory measurements of maximal oxygen consumptions, maximum heart rates and
      lactate thresholds were performed on 9 soccer players who played at Regional
      level. For test and retest field sessions, the exercise intensities were
      calculated from heart rate monitoring and match analysis (number of actions,
      consecutive passes, players involved in a single action) was performed. RESULTS:
      No significant differences were found in heart rate frequency distributions
      between test and retest sessions. Statistically significant differences in
      frequency distributions of heart rate were found only between the 3 min and 8 min
      drills played on the 40x50 m pitch. Regarding exercise intensity, significant
      differences (P<0.01) were found for pitch dimension, with higher intensities
      shown during the 30x40 m pitch trials. When technical data were related to time
      units, no differences were found among experimental settings. CONCLUSIONS: These
      data indicate that coaches could better modulate the training intensity by
      varying the pitch dimension, with the smaller individual playing area (30x40 m)
      having a large impact on the metabolic demands of exercise.

PMID- 16596098
TI  - The application of soccer performance testing protocols to the non-elite player.
AB  - AIM: The application of performance testing for the evaluation of non-elite
      soccer players has received little attention. The purpose of this investigation
      was to use tests developed for elite soccer players to evaluate performance in
      non-elite soccer players and compare performance test results between elite
      (literature) and non-elite (data) players. METHODS: Thirteen male soccer players
      volunteered to participate. The tests included a treadmill VO2max test, 20 m
      sprint, vertical jump (VJ), 30 s Wingate cycle ergometer test, the Loughborough
      Intermittent Shuttle Test (LIST), and 2 20-m multi-stage shuttle runs to
      exhaustion (fatigue test). Actual VO2max (absolute and relative) scores were
      correlated with the estimated VO2max scores (fatigue test), 20 m sprint, VJ, and
      30 s Wingate using a Pearson's product-moment correlation. A paired t-test was
      conducted on the fatigue test trials. RESULTS: Non-significant relationships were
      observed between actual VO2max scores and estimated VO2max from the fatigue test
      (absolute and relative terms). Non-significant relationships were also observed
      between peak and average power output (Wingate), 20 m sprint, and VJ. Mean heart
      rates (HRs) throughout the LIST was 165+/-7 bpm, which represented 88% of HRmax.
      CONCLUSIONS: The results of this study demonstrate that to elicit physiological
      differences between elite and non-elite players, assessment must include both an
      aerobic and anaerobic component.

PMID- 16596099
TI  - Effects of static stretching on leg power during cycling.
AB  - AIM: This study investigated the effects of warm-up involving static stretching
      on leg power. It was expected that the inclusion of static stretching in the warm
      up would decrease leg power. METHODS: Twenty-seven healthy volunteers (16 male,
      11 female) participated in the study. A prospective, repeated measures design was
      implemented where volunteers underwent 2 testing sessions at least 24 hours
      apart. One testing session involved a control warm-up (5 min submaximal cycling)
      followed by 4 10-s leg power tests at 5, 20, 40 and 60 min postwarm-up. For the
      other testing session, the subjects performed 5 min of submaximal cycling
      followed by 15 min of lower body static stretching and then the four leg power
      tests. Relative peak power, time to peak power and relative total work were
      measured for each leg power test. RESULTS: Peak power and total work were
      significantly greater after the static stretching warm-up compared to the control
      warm-up on all power tests. Peak power was achieved more quickly for the static
      stretching warm-up compared to the control warm-up on the 5 min test only.
      CONCLUSIONS: A warm up that includes static stretching has beneficial effects on
      anaerobic power events in comparison to submaximal cycling alone.

PMID- 16596100
TI  - The effect of active warm-up and stretching on the flexibility of adolescent
      soccer players.
AB  - AIM: The purpose of the investigation was to examine in field conditions the
      acute effects of passive stretching after a general warming-up bout as well as
      the effects of passive stretching alone. METHODS: Eighteen adolescent team soccer
      players participated in this study performing 3 different flexibility-training
      protocols in separate training sessions. In the first treatment stretching
      protocol a general warm-up was performed where subjects jogged for 20 minutes.
      The second treatment stretching protocol consisted of the same general warm-up
      followed by passive stretching of the lower extremities and the trunk, whereas
      the third and final treatment stretching protocol consisted of passive stretching
      alone, without any jogging. Passive range of joint motion was examined in hip
      flexion, hip extension, hip abduction, ankle dorsiflexion, knee flexion and trunk
      flexion using a goniometer and a flexometer. RESULTS: The general warming-up
      session induced a significantly increased range of motion only at the ankle
      dorsiflexion joint (P<0.05). Results also suggest that passive stretching alone
      and passive stretching after a general warming-up bout both induced a
      significantly increased range in all lower extremity joints and trunk flexion
      (P<0.001). CONCLUSIONS: Improvements in flexibility are observed after passive
      muscle elongation, irrespective of warming-up.

PMID- 16596101
TI  - The characteristics of simple muscle power by gripping: gender differences and
      reliability of parameters using various loads.
AB  - AIM: There are few studies on muscle power during local muscle contractions with
      a small range of motion such as in gripping. The purposes of this study were to
      clarify the properties of the developmental phase based on time series of muscle
      power output, the reliability of the parameters, their relationships and the load
      intensity derived peak power by gender differences, and to examine the
      possibility of evaluating muscle power using gripping. METHODS: Fifteen young
      males and 15 females participated in this study. Based on a crossover
      experimental design, each subject carried out 2 explosive grips at 20%, 30%, 40%
      and 50% loads of maximal using a voluntary grip contraction (MVC). The grip
      contraction velocities, sampled at 100 Hz, were measured accurately using a power
      instrument with an accelerometer. Muscle power curves were drawn from the product
      of the velocity and the set-up load. RESULTS: The cross-correlation coefficients
      between the trials for the average curve of the time-series moving distance, the
      velocity, and the power in any load were very high (over 0.95) in both genders.
      The reliability of each parameter was mostly good in both genders (intraclass
      correlation coefficient, ICC>0.75). The peak power curve differed between
      genders, and the curve around the peak value in females was irregular.
      CONCLUSIONS: A gender difference was found in the maximal power and the
      properties of the power curve. The maximal muscle power appeared at 30-50% MVC in
      males, and at 20-40% MVC in females. The peak power during the whole contraction,
      and the time to peak may reflect the conditions throughout the whole of the
      contraction. The new device used in this study to evaluate local regional muscle
      power (grip) is a very reliable and useful tool.

PMID- 16596102
TI  - Gender differences in the progression of metabolic responses during incremental
      exercise.
AB  - AIM: The present investigation was undertaken to elucidate the differences in the
      progression of metabolic responses during incremental exercise between men and
      women of similar maximal aerobic capacity. METHODS: Twenty males and 20 females
      served as subjects for the study. Each subject was randomly assigned to perform a
      graded exercise test on either a cycle ergometer or a treadmill. Of the 20
      subjects within each gender, 10 were tested on the cycle ergometer, whereas the
      other half was tested on the treadmill. During each test, absolute VO2, relative
      VO2, and HR were recorded during the last 15 seconds of every minute throughout
      the test. These variables were then plotted separately as a function of work rate
      so that a best-fit linear regression equation was generated for each of the three
      plots. RESULTS: Under the cycle condition, we found no difference in slope of
      increment in absolute VO2 between genders. However, the slope of increment in
      relative VO2 and HR was greater (P<0.05) in women than men. A negative
      correlation (r=-0.858, P<0.05) was found between body mass and slope of increment
      in relative VO2 in men and women combined. Under the treadmill condition, the
      slope for absolute VO2 were greater (P<0.05) in men than women. However, in terms
      of relative VO2 and HR, no between-gender differences were observed in the slope
      of increment. A positive correlation (r=0.769, P<0.05) was found between body
      mass and slope of increment in absolute VO2 in men and women combined.
      CONCLUSIONS: These results indicate that the progression of metabolic responses
      during incremental exercise differs between men and women despite a similar
      fitness. These gender differences may be further attributed to body mass that
      seems to play a distinctive role when the incremental exercise is conducted on a
      cycle ergometer and treadmill.

PMID- 16596103
TI  - Relationship between physical activity and obesity in children and adolescents.
AB  - AIM: The purpose of the present study was to analyze the relationship between
      physical activity (PA) and obesity in Portuguese children and adolescents.
      METHODS: The sample consisted of 1341 children and adolescents (8-15 years of
      age), 634 males (age, 10.6+/-2.3 y; body mass, 40.6+/-12.7 kg; height, 1.431+/
      1.41 m) and 707 females (age, 10.9+/-2.4 y; body mass, 50+/-12.4 kg; height,
      1.428+/-1.32 m). The sample was divided into quartiles of percentage of body fat
      (%BF) and physical activity index (PAI), within age and gender. Children in the
      upper %BF quartile were defined as obese (arbitrary definition). Logistic
      regression for each PAI quartile was used to determine the odds ratio of obese
      children and adolescents (> or = P75 of %BF) in comparison to their non-obese
      counterparts (< P75 of %BF). RESULTS: Males in the lowest PAI quartile have an
      odds ratio of 2.1 of having obesity in relation to males in the highest PAI
      quartile. For females any significant result was found between PAI quartiles.
      CONCLUSIONS: The results obtained in this study add some data to the controversy
      of PA and obesity relationship youth. Logistical regression shows that males who
      have a lower PAI have an odds ratio of 2.1 of obesity, in comparison with males
      that have higher PAI. Those findings were not found in girls.

PMID- 16596104
TI  - The effects of a nucleotide supplement on salivary IgA and cortisol after
      moderate endurance exercise.
AB  - AIM: The aim of this work was to determine the ergogenic effects of a nucleotide
      supplement on salivary immunoglobulin A (SIgA) and cortisol (C) responses after
      prolonged endurance cycle exercise. METHODS: Fourteen moderately trained male
      subjects (mean body mass and VO2max) completed 2 90-min cycle ergometer trials
      (60% VO2max) prior to and after 60 days of either a nucleotide (E group, n=7) or
      placebo (P group, n=7) supplement. Each of the subjects provided an unstimulated
      saliva sample prior to and following the exercise for determination of SIgA and
      C. RESULTS: SIgA was significantly lower after exercise trials in both E and P
      groups (P<0.0001) prior to as well as after the supplementation period. However,
      SIgA was significantly higher (P<0.01) in the E group than the P group after
      supplementation. There were no significant (P>0.11) differences in pre-exercise C
      level. Postexercise C concentrations were significantly (P<0.001) higher than pre
      exercise levels in both groups of subjects. However, after the supplementation
      period, C concentration was significantly (P<0.0001) lower after exercise in E
      compared to P. CONCLUSIONS: This work suggests that a nucleotide supplement,
      given chronically may offset the hormonal response associated with demanding
      endurance exercise.

PMID- 16596105
TI  - The effect of creatine monohydrate supplementation on sprint skating in ice
      hockey players.
AB  - AIM: Creatine monohydrate supplementation is beneficial for enhancing high
      intensity exercise performance, especially activities that involve repeated
      sprints. Creatine monohydrate supplementation is common in ice-hockey players.
      The purpose of this study was to determine the effect of creatine monohydrate
      supplementation on sprint skating performance in Junior B and collegiate ice
      hockey players. METHODS: Seventeen ice-hockey players were randomly assigned to
      receive creatine (0.3 g/kg body mass/day for 5 days) or placebo. Before and after
      supplementation players performed repeated sprints to exhaustion on a skating
      treadmill (repeated 10-s sprints; 30-s rest between sprints) while blood lactate
      was simultaneously collected. The time to exhaustion on the treadmill test was
      calculated as total amount of time, including partial intervals, before the
      player reached exhaustion. Players were also tested for peak torque and average
      power during knee extension/flexion (3 sets of 10 reps; 60-s rest between sets)
      on an isokinetic dynamometer at 60 degrees/s. RESULTS: The change in time to
      exhaustion from before to after supplementation averaged 20.6+/-7 s in the
      creatine group and 21.9+/-13 s in the placebo group, with no differences between
      groups. Likewise, there were no differences between groups for changes in
      isokinetic peak torque and average power. There were no differences between
      groups over time for blood lactate changes during the repeated sprints on the
      treadmill. CONCLUSIONS: We conclude that creatine was not effective for improving
      performance in these ice-hockey players.

PMID- 16596107
TI  - The relationships between instrumented measurements of ankle and knee ligamentous
      laxity and generalized joint laxity.
AB  - AIM: The purpose of this study was to evaluate whether lower extremity joint
      laxity is a function of a particular joint and/or a generalizable characteristic
      (trait) of the person. Validated instrumented measurements of ankle and knee
      joint-specific laxity in the same individual were correlated to determine whether
      a relationship exists. In addition, ankle and knee joint-specific laxity were
      correlated with generalized joint laxity using the modified Beighton mobility
      index. METHODS: Fifty-seven male and female athletes were studied. We examined
      dominant ankle laxity using an ankle arthrometer and dominate knee anterior
      laxity using the KT 2000. The dominant ankle was loaded in anteroposterior (AP)
      drawer and inversion-eversion (I-E) rotation. Laxity was measured as total AP
      displacement (millimeters) after +/-125 N of applied force and total I-E rotation
      (degrees) was measured after +/-4 N x m of applied torque. The dominant knee was
      loaded with an anterior drawer and laxity (millimeters) was measured after manual
      maximum displacement. RESULTS: Non-significant correlations were observed among
      the test variables for generalized joint laxity (0.21 to 0.37; P>0.05) and
      instrumented ankle and knee joint laxity (0.19 to 0.21; P>0.05). When examined by
      gender, no statistically significant correlations (0.05 to 0.40; P>0.05) were
      found for either generalized laxity or instrumented ankle and knee joint laxity.
      CONCLUSIONS: These results imply that ankle and knee joint laxity are joint
      specific and not generalizable.

PMID- 16596106
TI  - Arthroscopic treatment of post-traumatic elbow stiffness.
AB  - AIM: The treatment of post-traumatic elbow stiffness has seen many important
      changes over the years, particularly through the development of arthroscopy,
      greater knowledge of anatomy and improvements in operative techniques, that
      reduce the incidence of complications and facilitate postoperative recovery. In
      this study mid-term clinical results of arthroscopy for post-traumatic elbow
      stiffness are evaluated in 15 sporting patients, with an average age of 32 years.
      METHODS: Eight patients reported post-traumatic stiffness due to fracture of the
      radial head, 3 to fracture-dislocation, 1 to fracture of the radial diaphysis
      complicated by osteosynthesis, and the remaining 3 patients to stress syndromes
      with osteochondral detachment. Surgical treatment consists in debridement,
      arthroscopic capsular release, and removal of bone fragments by arthroscopy.
      Patients were followed up from 4 up to 36 months, with a mean follow-up time of
      18 months. RESULTS: Results obtained have been good to excellent in 84% of cases
      with an average range in postoperative movement of 13 degrees-137 degrees and
      reduction in pain symptomatology. The statistic results obtained from this study,
      under the same conditions and with a confidence interval = 0.01, show that the
      treatment will have favorable outcomes in 63% of patients of entire population
      (0.6285<P<1). CONCLUSIONS: In light of our mid-term clinical results on a small
      series of cases, arthroscopic surgical treatment would appear to be an acceptable
      option in management of the post-traumatic stiff elbow.

PMID- 16596108
TI  - Osteochondrosis dissecans of the shoulder glenoid fossa diagnosed in four
      throwing athletes.
AB  - The aim of this study was to report 4 observations of osteochondrosis dissecans
      (OCD) of the shoulder glenoid fossa diagnosed in throwing athletes. A
      retrospective review of medical and radiological records of throwing athletes,
      performed for the period 1992 to 2002, revealed 215 studies of the shoulder. The
      patients were elite throwing athletes suffering for recurrent shoulder pain. Four
      cases (1.86%) of OCD of the glenoid fossa were identified; conventional
      radiographs of the shoulder were taken for all patients followed by MR
      examination. All cases received a definitive surgical diagnosis.

PMID- 16596109
TI  - Late effects of cycle competition on arterial stiffness. A preliminary study.
AB  - AIM: The purpose of this study was to examine the effects of a cycle competition
      on the large arteries stiffness, 24-hours after the end of the effort. METHODS:
      Two males elite cyclists were studied before and after performing a stage-race.
      Their heart rate (HR) was measured continuously during the two competition days.
      The impact of the competition on their vascular system was determined using the
      measure of pulse wave velocity (PWV), an index of regional arterial stiffness. HR
      and blood pressure were also measured before and 24-hours postexercise. RESULTS:
      During the race, mean cyclists HR were relatively similar. Changes in PWV and HR
      were found after competition: these measures increased for the offensive subject
      and decreased for the other. CONCLUSIONS: Despite their involvement in the same
      cycling competition, we suggest that the long-term effects induced by effort on
      arterial stiffness were inverted according to the subject's comportment during
      the race. This study should be completed by others measures in order to precise
      our results and to precise the possible link between arteries stiffness and the
      recovery kinetic process, both depending on the cardiovascular autonomic nervous
      system control.

PMID- 16596111
TI  - Forced expiratory volume in one second and peak expiratory flow rate values in
      non-professional male tennis players.
AB  - AIM: Forced expiratory volume in 1 second (FEV1) is a reliable and easily
      measured lung function index, which is nowadays used for early detection of
      chronic obstructive pulmonary disease. It has also been established recently as
      an important predictor of all-cause, cardiovascular and cerebrovascular morbidity
      and mortality in the Western World. Similar implications have been made with
      regard to peak expiratory flow rate (PEFR). The present study was designed in
      order to compare the FEV1 and PEFR values of non-professional, smoking and non
      smoking male athletes to those predicted for the general, non-athlete population.
      METHODS: A total of 141 non-professional tennis players aged 30-74 years were
      studied (99 smokers and 42 non-smokers). FEV1 and PEFR of all men were measured
      by means of a one flow spirometer, and compared to those predicted for their age
      and height, based on formulas for the non-athlete, healthy, non-smoking
      population. RESULTS: Non-professional tennis players had significantly higher
      FEV1 and PEFR values, compared to FEV1 and PEFR predicted, respectively. No
      statistically significant difference was observed between smokers and non
      smokers. CONCLUSIONS: Our study confirms that even moderate physical activity,
      such as non-professional tennis, can improve FEV1 and PEFR values, maintaining a
      normal respiratory function, which is a strong predictor of reduced
      cardiovascular and overall morbidity and mortality. FEV1 and PEFR are easy to
      measure parameters that should be used more often for the assessment of general
      health status.

PMID- 16596110
TI  - Cardiorespiratory fitness in relation to self-reported physical function in
      cancer patients after chemotherapy.
AB  - AIM: The aim of this study was to estimate the association between objective
      cardiorespiratory fitness (CRF) and subjective self-reported physical function,
      taking into account the influence of mental distress. We hypothesized an
      association between these parameters, since they might be thought to measure
      parts of the same phenomenon. METHODS: Approximately 1 month after
      discontinuation of all primary treatment, 90 cancer patients aged 18-50 years
      treated with chemotherapy were surveyed. CRF was determined by the Astrand
      Ryhming indirect cycle ergometer test, which indicate peak VO2 in mL x kg(-1) x
      min(-1) (predicted VO2max). Self-reported physical function was assessed by The
      European Organisation for Research and Treatment of Cancer Core Quality of Life
      Questionnaire (EORTC QLQ-C30). The relation between VO2max and self-reported
      physical function was estimated by multiple linear regression. Mental distress
      (assessed by The Hospital Anxiety and Depression scale), age, gender, body mass
      index (BMI), time from treatment to physical test and diagnoses were included as
      potential confounders. RESULTS: There was no association between predicted VO2max
      and self-reported physical function. Mental distress was negatively associated
      with self-reported physical function (P<0.001), but is not associated with
      predicted VO2max. CONCLUSIONS: The results suggest that predicted VO2max does not
      reflect self-reported physical function and vice versa in cancer patients after
      chemotherapy. If information about cardiac and/or pulmonary status is required,
      direct or indirect measures of VO2max should be used.

PMID- 16596112
TI  - Anaerobic power performance and the menstrual cycle: eumenorrheic and oral
      contraceptive users.
AB  - AIM: The purpose of this project was to compare the impact of the menstrual cycle
      on short-term, high intensity (power) performance in active females who either
      had normal menstrual cycles (NOC) or who were using oral contraceptives (OC).
      METHODS: Subjects (7 NOC, 17 OC) completed a Margaria-Kalamen staircase test and
      a Wingate cycle test on 3 occasions: one for familiarization and the other two
      trials (random order) during menses (MEN) or luteal (LUT) phase. Phase was
      documented by urinary luteinizing hormone for the NOC. RESULTS: There were no
      significant differences between MEN and LUT in the NOC group on the Wingate test
      (n=7) for any of the following: peak power (P=0.33), peak power per kg body
      weight (P=0.37), anaerobic capacity (P=0.37), anaerobic capacity per kg body
      weight (P=0.42), power decline (P=0.36), power decline per kg body weight
      (P=0.35). Also there were no significant differences in power (P=0.95) for the
      Margaria-Kalamen test (n=6). There were no significant differences between MEN
      and LUT in the OC group for any of the following variables calculated from the
      subjects' performance on the Wingate test (n=17): peak power (P=0.39), peak power
      per kg body weight (P=0.36), anaerobic capacity (P=0.42), anaerobic capacity per
      kg body weight (P=0.36), power decline (P=0.57), power decline per kg body weight
      (P=0.66). Also there were no significant differences in power (P=0.44) for the
      Margaria-Kalamen test (n=11). CONCLUSIONS: For a moderately active group of
      women, anaerobic power performance was not influenced by menstrual cycle phase in
      either NOC or OC users.

PMID- 16596113
TI  - Plasma proinsulin, C-peptide and sex hormone concentrations in regularly
      menstruating premenopausal females with ovulatory and anovulatory menstrual
      cycles.
AB  - AIM: Highly active females are at risk of athletic menstrual irregularities
      including anovulatory menstrual cycles, oligomenorrhea and even amenorrhea. On
      the other hand, the functional relationship between endocrine pancreas and
      ovaries is supported by numerous studies indicating that disturbed female sex
      hormone secretion coexists with insulin resistance and glucose intolerance.
      However, the relationship between circulating beta islet and ovarian hormones in
      regularly menstruating active women with ovulatory and anovulatory menstrual
      cycle has not been studied. METHODS: A total of 32 regularly menstruating women
      participated in the study. Prospective subjects monitored their BBT for 3 months
      before the study. The determination of plasma progesterone levels between days 5
      8 and again between days 19-22 of the menstrual cycles made possible the
      classification of subjects as ovulating or non-ovulating. Plasma 17-beta
      estradiol, testosterone, insulin, proinsulin, C-peptide and glucose
      concentrations were assayed on the same menstrual cycle days as progesterone.
      RESULTS: There were no differences in circulating insulin, C-peptide and glucose
      between non-ovulating and ovulating women. In contrast, in non-ovulating subjects
      plasma proinsulin concentrations between days 19-22 were slightly, but
      significantly higher than between days 5-8 of the menstrual cycle (P<0.05).
      Exclusively in non-ovulating women significant and positive correlation was noted
      between circulating proinsulin and 17-beta-estradiol in data collected from both
      days 5-8 and 19-22 of the menstrual cycle (P<0.008). CONCLUSIONS: Our results
      indicate that in the face of low circulating progesterone and subsequent
      anovulation circulating 17-beta-estradiol slightly, but significantly, affect
      either pancreatic beta-cell biosynthetic activity or proinsulin hepatic and/or
      renal clearance.

PMID- 16596114
TI  - Exercise during late-follicular menstrual phase: influence on immune parameters.
AB  - AIM: The purpose of this study was to examine whether training status and plasma
      hormones (estradiol--E2, progesterone--P, luteinizing hormone--LH, and follicle
      stimulating hormone--FSH) have an effect on selected immune indexes during or
      following an acute bout of exercise. METHODS: Seven female triathletes (TRI) and
      7 recreationally active (REC) females were randomly assigned to rest (RE) and
      exercise (EX) trials during the late-follicular menstrual phase (LF). The EX was
      1 hour of cycling at 63.1+/-6% VO2peak (TRI) and 61+/-5.1% VO2peak (REC) and RE
      was 1 hour of sitting. Blood was drawn for both trials at baseline (0H), 1 hour
      (1H), and at 3 hours (3H). RESULTS: Positive correlations were found between E2
      and CD19+ cells for both groups as well as P and CD8+ cells for the REC group. E2
      increased during EX and returned to baseline at 3HEX for both groups, however, LH
      remained elevated at 3HEX for REC. There were significant exercise time effects
      for CD3+, CD4+, CD8+, and CD3- CD16+ CD56+ cells. The NCMC and 1:1 were elevated
      at 1HEX for both groups and returned to baseline by 3HEX. During RE, CD3- CD16+
      CD56+ cell numbers for both groups and NCMC for REC remained elevated at 3HRE.
      CONCLUSIONS: E2 and P correlated with CD19+ and CD8+ cells, respectively.
      Although there were transient exercise-induced changes in immune indexes and E2
      and LH, with LH remaining elevated at 3HEX for REC, both training groups elicited
      similar responses for plasma hormones, lymphocyte subpopulations, and NCMC.

PMID- 16596115
TI  - Daily changes of salivary secretory immunoglobulin A and appearance of upper
      respiratory symptoms during physical training.
AB  - AIM: It is well known that highly trained athletes suffer from a high incidence
      of upper respiratory tract infections (URTI). Secretory immunoglobulin A (SIgA)
      is a major effector of mucosal surface protection against microorganisms causing
      URTI. Although several studies have investigated the relationship between falls
      in SIgA levels and appearance of URTI symptoms, the relationship is not yet
      clear. METHODS: We prospectively investigated the relationship between daily
      changes in SIgA and appearance of URTI symptoms in collegiate soccer players
      during a training period of 2 months. RESULTS: Five of 12 subjects exhibited URTI
      symptoms during the study period. The SIgA level did not significantly decrease
      before appearance of URTI symptoms. However, the saliva flow rate and SIgA
      secretion rate tended to decrease 3 days before the appearance of URTI symptoms
      compared to that in the non-infection period (31.3+/-19, -42.2+/-20.6%,
      respectively). CONCLUSIONS: We could not demonstrate a significant relationship
      between decreased SIgA levels and appearance of URTI symptoms during the training
      period. However, our findings suggest that monitoring of SIgA secretion rate may
      be useful for assessment of risk status of athletes for URTI.

PMID- 16596116
TI  - Relationship between salivary IgA secretion and upper respiratory tract infection
      following a 160-km race.
AB  - AIM: The relationship between salivary IgA secretion rate and upper respiratory
      tract infection (URTI) was studied in 155 ultramarathoners (126 males, 29
      females, mean age 46.5+/-0.7 y) who had qualified to run the 160-km 2003 Western
      States Endurance Run. METHODS: Subjects provided saliva samples during
      registration, held the morning before the race, and within 5-10 minutes postrace
      (mean race time, 26.2+/-0.3 h). Unstimulated saliva was collected by
      expectoration for 4 minutes into 15-mL plastic, sterilized vials. Runners
      finishing the race and providing pre- and postrace saliva samples (n=106) turned
      in a health log specifying URTI episodes and severity of symptoms for the 2-week
      period following the race. RESULTS: The total volume of saliva that the runners
      was able to expectorate during sample collection decreased 51% postrace compared
      to prerace values (P<0.001). Saliva protein concentration increased 20% (P<0.001)
      while the saliva protein IgA concentration decreased 10% (P<0.05). Salivary IgA
      secretion rate decreased 46% when comparing pre- to postrace values (P<0.001).
      Twenty-four percent of the runners finishing the race and providing salivary
      samples reported an URTI episode lasting 2 days or longer during the 2-week
      period following the race (mean number of days with symptoms was 5.4+/-0.6 days).
      The decrease in salivary IgA secretion rate (pre- to postrace) was 53% greater in
      the 25 runners reporting URTI (-355+/-45 microg/min) compared to the 81 runners
      not reporting URTI (-232+/-37 microg/min), (P=0.04). CONCLUSIONS: In summary,
      nearly 1 in 4 runners reported an URTI episode during the 2-week period following
      a 160-km race, and the decrease in salivary IgA secretion rate was significantly
      greater in these runners compared to those not reporting URTI.

PMID- 16596117
TI  - The values of immature reticulocytes fraction in elite athletes measured by means
      of two different technologies are concordant.

PMID- 16596118
TI  - Evidence from autoimmune thyroiditis of skewed X-chromosome inactivation in
      female predisposition to autoimmunity.
AB  - The etiologic factors in the development of autoimmune thyroid diseases (AITDs)
      are not fully understood. We investigated the role of skewed X-chromosome
      inactivation (XCI) mosaicism in female predisposition to AITDs. One hundred and
      ten female AITDs patients (81 Hashimoto's thyroiditis (HT), 29 Graves' disease
      (GD)), and 160 female controls were analyzed for the androgen receptor locus by
      the HpaII/polymerase chain reaction assay to assess XCI patterns in DNA extracted
      from peripheral blood cells. In addition, thyroid biopsy, buccal mucosa, and hair
      follicle specimens were obtained from five patients whose blood revealed an
      extremely skewed pattern of XCI, and the analysis was repeated. Skewed XCI was
      observed in DNA from peripheral blood cells in 28 of 83 informative patients
      (34%) as compared with 10 of 124 informative controls (8%, P<0.0001). Extreme
      skewing was present in 16 patients (19%), but only in three controls (2.4%,
      P<0.0001). The buccal mucosa, and although less marked, the thyroid specimens
      also showed skewing. Analysis of two familial cases showed that only the affected
      individuals demonstrate skewed XCI patterns. Based on these results, skewed XCI
      mosaicism may play a significant role in the pathogenesis of AITDs.

PMID- 16596119
TI  - Identification of cis- and trans-acting factors possibly modifying the risk of
      epimutations on chromosome 15.
AB  - In the majority of patients with a chromosome 15 imprinting defect (ID) causing
      Prader-Willi syndrome (PWS) or Angelman syndrome (AS), the defect is a primary
      epimutation that occurred spontaneously in the absence of a DNA mutation. We have
      investigated whether common DNA sequence variants in the bipartite imprinting
      centre (IC) are associated with an increased susceptibility to imprinting
      defects. We have determined the haplotype structure of the IC and found that the
      two IC elements called 'PWS-SRO' and 'AS-SRO' lie on separate haplotype blocks.
      To identify susceptible IC sequence variants, we have used the transmission
      disequilibrium test. While we did not observe preferential transmission of a
      paternal allele or haplotype in 41 PWS-ID trios, we found a trend for
      preferential maternal transmission of one AS-SRO haplotype (H-AS3) in 48 AS-ID
      trios (P=0.058) and could identify two sequence variants in H-AS3 that are
      responsible for this effect. We also obtained tentative evidence that
      homozygosity for the 677C>T variant of the 5,10-methylenetetrahydrofolate
      reductase (MTHFR) gene on chromosome 1 might increase the risk of a maternal
      imprinting defect: the frequency of the TT genotype was significantly higher in
      the mothers of the AS patients with an imprinting defect than in the patients'
      fathers or the general population (P=0.028). Our findings suggest that women with
      the IC haplotype H-AS3 or homozygosity for the MTHFR 677C>T variant may have an
      increased risk of conceiving a child with an imprinting defect, although the
      absolute risk is low.

PMID- 16596120
TI  - Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model
      of thromboembolic stroke.
AB  - Uric acid is a natural antioxidant that protects the brain in a model of
      transient focal ischemia in rats. Here we sought to investigate whether uric acid
      was protective in a model of thromboembolic brain ischemia in rats, and whether
      the global benefit of recombinant tissue plasminogen activator (rt-PA) was
      improved by the combined treatment. Adult male Sprague-Dawley rats underwent
      either ischemia by thromboembolic middle cerebral artery occlusion (MCAO) or sham
      operation. Uric acid (16 mg/kg) was injected intravenously (i.v.). 20 mins after
      MCAO, whereas rt-PA (10 mg/kg) was administered i.v. at 3 h. A group of rats
      received the combined treatment. Rats underwent two neurologic examinations (30
      mins and 24 h after MCAO). At 24 h, infarct volume was measured and brain
      neutrophil infiltration and protein tyrosine nitration were assessed. Treatment
      with either uric acid or rt-PA reduced infarct volume versus controls (P<0.05).
      The protective effect against brain ischemia was greater after cotreatment of
      uric acid with rt-PA (P<0.001), which added further benefit to rt-PA alone
      (P<0.05). The neurologic score worsened during the first 24 h in treatment
      controls, whereas it improved in rats receiving uric acid and/or rt-PA. Uric acid
      strongly reduced ischemia-induced tyrosine nitration, but it was more effective
      alone than combined with rt-PA, suggesting that reperfusion enhances
      nitrotyrosine formation. All treatments reduced postischemic brain neutrophil
      infiltration. These results show that uric acid administered early after
      thromboembolic stroke is neuroprotective in the rat brain, as it reduces infarct
      volume, ameliorates the neurologic function, attenuates the inflammatory
      response, and extends the benefits of rt-PA.

PMID- 16596124
TI  - Creating a unified Europe: losing identity and visibility for a greater profit?

PMID- 16596121
TI  - Therapeutic benefit of bone marrow stromal cells administered 1 month after
      stroke.
AB  - Bone marrow stromal cells (BMSCs) facilitate functional recovery in rats after
      stroke when administered acutely (1 day) or subacutely (7 days). In this study,
      we postponed the time of cell transplantation to 1 month after stroke. Female
      retired breeder rats were subjected to 2 h of middle cerebral artery occlusion
      (MCAo). Male BMSCs (3 x 10(6)) or phosphate-buffered saline were administered
      intravenously, and the animals were killed 3 months later. An additional
      population of nontreated rats was killed at 1 month after MCAo. Significant
      recovery of behavior was found in BMSC-treated rats beginning at 1 month after
      cell injection in the modified neurologic severity score test and the adhesive
      removal test compared with control animals (P<0.05). In situ hybridization showed
      that BMSCs survived and preferentially localized to the ipsilateral hemisphere.
      Double staining revealed that approximately 13% and 6% Y-chromosome-positive
      cells expressed the astrocyte marker, glial fibrillary acidic protein, and the
      neuronal marker, microtubule-associated protein-2, respectively. In addition,
      BMSC treatment reduced scar thickness, and increased the number of proliferating
      cells and oligodendrocyte precursor cells along the subventricular zone in the
      ipsilateral hemisphere. Expression of the chemokine stromal-cell-derived factor-1
      (SDF-1) was significantly increased along the ischemic boundary zone compared
      with the corresponding areas in the contralateral hemisphere at 1 month and 4
      months (P<0.01) after stroke. The SDF-1 receptor, CXC-chemokine receptor-4
      (CXCR4), was expressed in BMSCs both in vitro and in vivo. Our data show that the
      time window of BMSC therapy is at least 1 month after stroke; the interaction of
      SDF-1/CXCR4 may contribute to the trafficking of transplanted BMSCs.

PMID- 16596125
TI  - EGFR mutations and molecularly targeted therapy: a new era in the treatment of
      lung cancer.

PMID- 16596122
TI  - Mucosal tolerance to E-selectin and response to systemic inflammation.
AB  - Mucosal tolerance to E-selectin has been shown to prevent stroke and reduce brain
      infarcts in experimental stroke models. However, the effective E-selectin dose
      range required to achieve mucosal tolerance and the precise mechanisms of
      neuroprotection remain unclear. We sought to examine the mechanisms of
      cytoprotection using gene expression profiling of tissues in the setting of
      mucosal tolerance and inflammatory challenge. Using spontaneously hypertensive
      rats (SHRs), we achieved immune tolerance with 0.1 to 5 microg E-selectin per
      nasal instillation and observed a dose-related anti-E-selectin immunoglobulin G
      antibody production. We also show the distinct patterns of gene expression
      changes in the brain and spleen with the different tolerizing doses and
      lipopolysaccharide (LPS) exposure. Prominent differences were seen with such
      genes as insulin-like growth factors in the brain and downregulation of those
      encoding the major histocompatibility complex class I molecules in the spleen. In
      all, mucosal tolerance to E-selectin and subsequent exposure to LPS resulted in
      significant tissue changes. These changes, while giving an insight to the
      underlying mechanisms, serve as possible targets for future studies to facilitate
      translation to human clinical trials.

PMID- 16596139
TI  - What is the risk of cardiac morbidity with adjuvant radiotherapy for breast
      cancer?

PMID- 16596140
TI  - Using genetic analysis to individualize preventive measures for breast and
      ovarian cancers.

PMID- 16596138
TI  - Is trastuzumab active following conventional adjuvant chemotherapy in HER2
      positive early breast cancer?

PMID- 16596141
TI  - Factors predictive for response of follicular and mantle-cell lymphoma to
      rituximab.

PMID- 16596142
TI  - Does regular use of aspirin reduce the risk of colorectal cancer?

PMID- 16596143
TI  - Chemoradiation paradigm for the treatment of lung cancer.
AB  - For the treatment of locoregional advanced stage III non-small-cell lung cancer,
      when chemotherapy is added sequentially to radiotherapy it acts systemically and
      is aimed at reducing distant metastases. Concurrent chemotherapy and radiation,
      however, is intended to enhance the locoregional efficacy of this modality.
      Combined effects of these modalities are based on their different toxicity
      profiles, leading to a reduced toxicity : efficacy ratio of the combination.
      Controlled trials investigating this additive approach indicate that concurrent
      application of chemotherapy and radiotherapy results in a small but significant
      benefit for locoregional control, which translates into a small but measurable
      survival benefit. This benefit is most evident when looking at 3-year or 5-year
      overall survival rates, when it is of clinical significance. The use of single
      agent cisplatin has already demonstrated major radiosensitizing effects whereas
      the radiosensitizing properties of concurrent application of the single-agent
      carboplatin have not been observed in controlled trials. Newer drugs such as
      vinorelbine, the taxanes and gemcitabine might enhance this effect, although no
      improvement has been observed in randomized controlled trials comparing such
      regimens with single-agent cisplatin. New 'targeted' agents might synergize with
      ionizing irradiation and provide an interesting rationale concerning combined
      modality therapy, but this hypothesis awaits prospective clinical evidence from
      randomized controlled trials.

PMID- 16596144
TI  - Nonmetastatic renal-cell carcinoma: is it really possible to define rational
      guidelines for post-treatment follow-up?
AB  - Defining rational follow-up guidelines in patients treated for cancer is
      important, from both a medical and an economical perspective. Renal-cell
      carcinoma is reputed to be unpredictable in its course and only a few, and often
      contradictory, follow-up guidelines exist for patients treated for nonmetastatic
      renal-cell carcinoma. Recent advances in tumor biology have contributed to a
      better understanding of this cancer and have indicated that personalized follow
      up regimens, based on tumor and host molecular characteristics, might be possible
      in the near future.

PMID- 16596146
TI  - Extramedullary relapse of multiple myeloma presenting as hematemesis and melena.
AB  - BACKGROUND: A 60-year-old woman with multiple myeloma relapsed after a good
      partial response to high-dose chemotherapy (melphalan 200 mg/m(2)) and autologous
      stem-cell transplantation, followed by thalidomide and prednisolone maintenance
      therapy. She presented with hematemesis and melena following salvage chemotherapy
      with dexamethasone, cyclophosphamide, etoposide, cisplatin, and rescue therapy
      with single-agent bortezomib. INVESTIGATIONS: Physical examination, laboratory
      investigations, gastroscopy, 2-[(18)F]fluoro-2-deoxyglucose-PET (FDG-PET), breast
      biopsy and histology. DIAGNOSIS: Multifocal extramedullary relapse of multiple
      myeloma involving the stomach and duodenum. MANAGEMENT: High-dose infusion of
      omeprazole, blood product support, palliative analgesics and anxiolytic agents.

PMID- 16596145
TI  - Therapy Insight: venous-catheter-related thrombosis in cancer patients.
AB  - Central venous catheters (CVCs) have improved the management of patients with
      cancer substantially, by facilitating chemotherapy and supportive therapy. The
      use of CVCs is associated with complications such as infection and upper-limb
      deep vein thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related
      to the use of CVCs ranges between 2% and 4%. In the most recent study, the
      incidence of CVC-related thrombosis, as screened by venography, was approximately
      18% in the absence of prophylaxis. In cancer patients with CVC-related UL-DVT,
      the incidence of clinically overt pulmonary embolism was between 15% and 25%, and
      the incidence of autopsy-proven pulmonary embolism was up to 50%. Pathogenic
      factors for CVC-related thrombosis include vessel injury caused by the CVC
      insertion procedure, venous stasis because of the indwelling CVC, and
      hypercoagulability associated with cancer. Recent studies have not confirmed a
      benefit for prophylaxis with antithrombotic agents for CVC-related thrombosis.
      The recommended treatment for CVC-related thrombosis is based on long-term
      anticoagulant therapy, with or without catheter removal.

PMID- 16596148
TI  - Development of a chronic disease risk factor index and identifying population
      subgroups at risk using New South Wales Population Health Survey 2002 data.

PMID- 16596149
TI  - Admission to hospital for sunburn and drug phototoxic and photoallergic
      responses, New South Wales, 1993-94 to 2000-01.

PMID- 16596150
TI  - Researching culture and health: variables used to identify culturally diverse
      groups in New South Wales.

PMID- 16596151
TI  - EpiReview: Epidemiology of newly diagnosed HIV infection in New South Wales, 1994
      2003.

PMID- 16596152
TI  - Bug Breakfast in the Bulletin: Blood-borne viruses in correctional facilities.

PMID- 16596153
TI  - FactSheet: Infectious mononucleosis.

PMID- 16596154
TI  - Communicable diseases report, New South Wales, for July and August 2005.

PMID- 16596155
TI  - Trends in the incidence of tuberculosis in possums and livestock, associated with
      differing control intensities applied to possum populations.
AB  - AIM: To determine the trap-catch index (an estimate of abundance) of brushtail
      possum (Trichosurus vulpecula) populations infected with bovine tuberculosis (Tb;
      Mycobacterium bovis) that must be achieved, and the length of time such an index
      must be maintained, for Tb to be eliminated from possum populations and adjacent
      livestock. METHODS: Between 1997-1998 and 2000-2001, trap-catch surveys of possum
      populations naturally infected with Tb and subjected to population-control
      measures were undertaken at four forest sites and two farmland sites. At the same
      time, possum carcasses were collected at these sites and their Tb status
      determined, and all contiguous cattle and deer herds were Tb tested and abattoir
      slaughter data for these herds were interrogated. RESULTS: Trap-catch surveys
      indicated that numbers of possums on the farmland sites surveyed were usually
      very low and well below the control targets set (i.e. a 5% trap catch or
      approximately 0.5-1 possum/ha) for the study. In contrast, trap-catch surveys
      undertaken in forest sites indicated possum numbers were more variable, and often
      recovered rapidly from control operations to exceed control targets within 1-3
      years. The annual rate of recovery of possum populations in half of the forest
      population surveys undertaken exceeded published intrinsic rates of increase for
      possums. The overall prevalence of Tb in possum populations was < or =1.9% at 5/6
      sites, and was 6.5% at the sixth site. Juvenile possums infected with Tb were
      trapped within but near the edge of control zones and appeared to represent an
      immigrant source of infection. Mature infected possums survived control
      operations apparently by having home ranges in uncontrolled patches within
      control areas. Infection in possums appeared to be eliminated from one study site
      by the intensive control undertaken, but elimination at other sites appeared less
      likely. Levels of Tb in livestock on or adjacent to the study sites fell by at
      least 50% during the study, and cattle in one area tested clear for the first
      time in 20 years. CONCLUSIONS: Initial control of possums in forest appeared to
      achieve national control targets set by the Animal Health Board (AHB), despite
      trap-catch data often providing misleading population estimates. Such targets
      were often exceeded within 1-3 years. By comparison, possum control on farmland
      appeared to maintain populations at very low levels, while control on forest
      margins maintained populations at intermediate levels. Control was least
      effective in deep forest where human access was most difficult. Intensive
      population control measures appeared to have led to a reduced incidence of Tb in
      livestock at 3/4 sites, and elimination of Tb in livestock at one site. This
      result supports modelling studies that predict the eradication of Tb from possums
      through ongoing intensive control and may explain the lower success achieved with
      earlier less-intensive possum control.

PMID- 16596156
TI  - Genetic characterisation of bovine herpesvirus 1 in New Zealand.
AB  - AIM: To genotype bovine herpesvirus type 1 (BHV-1) isolates from cattle in New
      Zealand. METHODS: Twenty-eight BHV-1 isolates were collected from clinical
      samples from cattle over 28 years. They were characterised and compared using
      restriction endonuclease analysis (REA), and polymerase chain reaction (PCR) and
      DNA sequencing. RESULTS: Twenty-four isolates were classified as bovine
      herpesvirus subtype 1.2b (BHV-1.2b) by REA. The remaining four isolates were
      distinct from the others in REA profiles of one of the major enzymes (HindIII) by
      which the classification was made. However, these four isolates were closely
      related to others when the REA profiles of other restriction enzymes were
      studied, and therefore were regarded as divergent strains of BHV- 1.2b. All BHV-1
      isolates were detectable by PCR, and sequence analysis of selected PCR products
      did not indicate any significant differences between isolates. CONCLUSION: BHV
      1.2b appears to be the predominant strain of BHV-1 in cattle in New Zealand.
      There was no evidence that more virulent strains of BHV-1, e.g. subtype 1.1 and
      BHV type 5, are, or have been, present in New Zealand. Genetic variations exist
      among these BHV-1.2b isolates.

PMID- 16596157
TI  - Dose response effects of long-acting injectable vitamin B12 plus selenium (Se) on
      the vitamin B12 and Se status of ewes and their lambs.
AB  - AIM: To determine the effect of increasing doses of long-acting injectable
      vitamin B12 plus selenium (Se) given pre-mating on the vitamin B12 and Se status
      of ewes and their lambs from birth to weaning. METHODS: Four groups of 24 Poll
      Dorset ewes each were injected 4 weeks pre-mating with different doses of a long
      acting vitamin B12 + Se product, containing 3 mg vitamin B12 and 12 mg Se per ml.
      The treatment groups received 5 ml (15 mg vitamin B12 + 60 mg Se), 4 ml (12 mg
      vitamin B12 + 48 mg Se), 3 ml (9 mg vitamin B12 + 36 mg Se), or no vitamin B12 or
      Se (control). Twelve of the twin-bearing ewes per group were selected for the
      study. Efficacy of the product was evaluated from changes in the concentrations
      of vitamin B12 in serum and liver, and of Se in blood, liver and milk in the ewes
      during gestation and lactation, and in their lambs from birth to weaning. Pasture
      samples in paddocks grazed by the ewes and lambs were collected at about 2
      monthly intervals from 200-m transects. RESULTS: The flock was Se-deficient, as
      the mean initial concentration of Se in the blood of ewes was 182 (SE 20.3)
      nmol/L. Compared with untreated controls, all doses significantly (p < 0.01)
      increased concentrations of Se in the blood of ewes for at least 300 days.
      Selenium concentrations in milk were likewise increased throughout lactation, as
      were those in the blood and liver of lambs. The mean concentration of vitamin B12
      in the serum of ewes was initially > 1,000 pmol/L, but this decreased within 28
      days to < 460 pmol/L. Treatment with the 5-ml and 4-ml doses raised serum vitamin
      B12 concentrations of ewes for at least 176 days (p < 0.01), while their lambs
      had significantly greater concentrations of vitamin B12 in serum and liver for
      less than 37 days after birth. Tissue concentrations and duration of elevation of
      both vitamin B12 and Se were proportional to the dose administered. The mean
      concentrations of Se and cobalt (Co) in the pastures were 32 and 74 microg/kg dry
      matter (DM), respectively. CONCLUSIONS: Injecting ewes from a Se-deficient flock
      4 weeks prior to mating with 48 or 60 mg Se and 12 or 15 mg vitamin B12 increased
      and maintained the Se status of ewes for at least 300 days, and of their lambs
      from birth to weaning. The vitamin B12 status of ewes was increased for at least
      176 days and that of their lambs for less than 37 days. Due to the proportional
      nature of the response to increasing dosage, the dose rate of the formulation
      tested can be adjusted according to the severity of Se and Co deficiency in a
      flock. CLINICAL SIGNIFICANCE: A single subcutaneous injection of vitamin B12 + Se
      administered pre-mating to Se-deficient flocks is likely to prevent Se deficiency
      in ewes and their lambs until weaning, as well as increase the vitamin B12 status
      of ewes and their lambs until 5 weeks after lambing.

PMID- 16596158
TI  - Comparison of a camera - software system and typical farm management for
      detecting oestrus in dairy cattle at pasture.
AB  - AIM: To compare the sensitivity, specificity, predictive values and accuracy of
      detection of oestrus using a novel oestrus detection strip (ODS) and a camera
      software device (CSD) with typical farm management practices of visual
      observation and use of tail paint in dairy cattle at pasture. METHODS: Dairy cows
      (n = 480) in a seasonal-calving herd managed at pasture under typical commercial
      conditions in New Zealand were stratified by age, body condition score and days
      in milk, then randomly allocated to one of two groups prior to the planned start
      of mating (PSM). Tail paint was applied to all cows and oestrus detected by
      visual observation of oestrous behaviour and removal of paint, by farm staff. One
      group (n = 240) was fitted with ODS and also monitored for signs of oestrus using
      a CSD, while the Control group (n = 240) was monitored using tail paint and
      visual observations only. Cows detected in oestrus were artificially inseminated
      (AI), and pregnancy status determined using rectal palpation and ultrasonography,
      51-52 days after the end of a 55-day A period. Results of pregnancy diagnosis
      were used to confirm the occurrence of oestrus, and the sensitivity, specificity,
      predictive value and accuracy of detection of oestrus compared between oestrus
      detection methods. RESULTS: The sensitivity and accuracy of oestrus detection in
      the Control group, using visual observation and tail paint, were low. Compared
      with the Control group, detection of oestrus using the ODS and CSD resulted in
      greater sensitivity (85% vs 78%; p = 0.006), specificity (99.6% vs 98.0%; p <
      0.001), positive predictive value (PPV; 88% vs 51%; p < 0.001) and overall
      accuracy (99.0% vs 98.0%; p < 0.001). Negative predictive value (NPV) did not
      differ significantly between groups (99.4% vs 99.3%; p = 0.28). Pregnancy rate to
      first service was higher in the CSD group than in the Control group (72% vs 39%;
      p < 0.05). Use of the CSD significantly increased the cumulative proportion of
      cows pregnant to AI over the breeding period (p = 0.044). CONCLUSION AND CLINICAL
      RELEVANCE: The ODS and CSD was satisfactory for detection of oestrus in seasonal
      calving dairy herds grazing on pasture and could improve the sensitivity and
      accuracy of detection of oestrus in herds where these are low.

PMID- 16596159
TI  - Serotypes and analysis of distribution of Shiga toxin producing Escherichia coli
      from cattle and sheep in the lower North Island, New Zealand.
AB  - AIMS: To serotype a subset of Shiga toxin-producing Escherichia coli (STEC)
      isolates from cattle and sheep to determine whether any corresponding serotypes
      have been implicated in human diarrhoeal disease, both in New Zealand and
      worldwide, and to examine the distribution of STEC and enteropathogenic
      Escherichia coli (EPEC) amongst cattle (calves, heifers and dairy) and sheep
      (lambs, rams and ewes), to assess whether carriage of identified bacterial
      genotypes may be associated with a particular age of animal. METHODS: Recto-anal
      mucosal swabs (RAMS) were taken from 91 calves, 24 heifers and 72 dairy cattle,
      and 46 lambs, 50 ewes and 36 rams, from four sites in the Manawatu and Rangitikei
      regions of New Zealand. Strains of E. coli selected from primary isolation plates
      were subjected to a multiplex polymerase chain reaction (PCR), to determine the
      presence of Shiga toxin genes (stx1 and stx2) and the E. coli attaching and
      effacing gene (eae). RESULTS: Overall, 186/319 (58.3%) animals sampled were
      positive for stx1, stx2, or eae isolates. More sheep (43.9%) were stx1-positive
      than cattle (2.7%; p = 0.036), and amongst sheep more lambs and ewes were stx1
      positive than rams (p = 0.036). Amongst cattle, more calves and heifers were eae
      positive than dairy cows (p = 0.030). Two or more different STEC were isolated
      from at least 28 (9%) animals (three cattle and 25 sheep), based on their stx/eae
      genotype. Enterohaemolysin genes were found in 39/51 (76%) isolates serotyped.
      Twenty-one different serotypes were detected, including O5:H-, O9:H51, O26:H11,
      O84:H-/H2 and O149:H8 from cattle, and O26:H11, O65:H-, O75:H8, O84:H-, O91:H-,
      O128:H2 and O174:H8 from sheep; O84:H-, O26:H11, O5:H-, O91:H- and O128:H2
      serotypes have been associated with human disease. CONCLUSIONS: If nationally
      representative, this study confirms that cattle and sheep in New Zealand may be a
      major reservoir of STEC serotypes that have been recognised as causative agents
      of diarrhoeal disease in humans. Distribution of STEC and EPEC in cattle and
      sheep indicates that direct contact with, in particular, calves or their faeces,
      or exposure to environments cross contaminated with ruminant faeces, may
      represent an increased risk factor for human disease in New Zealand.

PMID- 16596160
TI  - Persistence, serodiagnosis and effects on semen characteristics of artificial
      Brucella ovis infection in red deer stags.
AB  - AIMS: To investigate the persistence of infection and serum antibody titres after
      infection of red deer (Cervus elaphus) stags with Brucella ovis, and compare
      these with those of rams. To assess the effects of recent and chronic infection
      on semen characteristics of stags. METHODS: Fourteen stags and eight rams were
      artificially infected with B. ovis by intravenous inoculation. Semen and blood
      samples were collected at approximately monthly intervals for 649 days. Semen
      samples were subjected to bacterial culture, and sera were tested for B. ovis
      antibodies using a complement fixation test (CFT) and an enzyme-linked
      immunosorbent assay (ELISA). At the end of the study, animals were slaughtered
      and reproductive organs subjected to bacterial culture. During the first and
      second breeding seasons, three and five semen samples, respectively, were
      evaluated from each stag for sperm motility and morphology. RESULTS: Twelve of 14
      (86%) stags and 6/8 (75%) rams developed a patent B. ovis infection and shed the
      organism in semen. All six infected rams continued to shed B. ovis in semen
      throughout the 649-day study period, and at slaughter B. ovis was isolated from
      the reproductive tract and urinary bladder. In contrast, 10/12 (83%) infected
      stags stopped shedding B. ovis in semen 103-342 days after inoculation, and the
      organism could not be isolated from their reproductive tracts at slaughter. The
      remaining two infected stags shed B. ovis in semen throughout the study period
      and the organism was isolated from their reproductive tracts at slaughter. All
      inoculated animals initially developed serum antibody titres detectable using the
      B. ovis CFT and ELISA. For infected stags, the diagnostic sensitivity of these
      tests was 100% for the first 166 days, but decreased to 50-90% after this. The
      diagnostic sensitivity for the infected rams was 100% throughout the study
      period. Infection in stags resulted in variable effects on semen characteristics.
      Eight of 12 (67%) infected stags had a mean sperm motility of < 50%, and < 60%
      mean normal sperm in the first year of infection. Seven of these stags had
      resolved the infection by the following breeding season, and there was a
      significant improvement in sperm motility and morphology. CONCLUSIONS: Stags are
      as susceptible as rams to experimental B. ovis infection. However, the majority
      of infected stags resolved the infection within a year, whereas rams remained
      infected for at least 649 days (22 months). Serology, using CFT and ELISA, was
      effective at detecting infection during the first 166 days in both species, but
      after this time was less effective at detecting infection in stags than in rams.
      Infection with B. ovis had variable but generally deleterious effects on the
      semen characteristics of stags, which resolved following resolution of the
      infection. Differences in the characteristics of the disease in stags compared
      with rams mean that different control methods are warranted for the two species.
      CLINICAL RELEVANCE: Most stags infected with B. ovis are likely to resolve the
      infection within a year, and semen characteristics return to levels acceptable
      for breeding. Serology is useful for detection of infection in the early stages
      of the disease, but once disease has been present in the herd for some time false
      negative reactions are likely to occur in individual stags.

PMID- 16596161
TI  - The effect of length of use of teaser rams prior to mating and individual
      liveweight on the reproductive performance of ewe hoggets.
AB  - AIM: To determine the effects of liveweight (LW) and duration of teasing with
      vasectomised rams prior to breeding on both the mating performance and pregnancy
      rate of ewe hoggets. METHODS: Five hundred and forty-six (1/2) Romney x (1/4)
      Texel x (1/4) Finnish Landrace ewe hoggets were weighed and randomly assigned to
      one of three treatment groups: either exposed to five harnessed vasectomised
      (teaser) rams for 17 days prior to the breeding period (T17; n =181); exposed to
      five harnessed teaser rams for 8 days prior to the breeding period (T8; n = 184);
      or not exposed to teasers (unteased; n = 181). Harnessed entire rams of the same
      breed were then introduced for the duration of two oestrous cycles. Using crayon
      marks, hoggets were identified as having been mated in the first 5 days, Days 6
      10, Days 11-17, during the first 17 days only, during both 17-day periods, during
      the second 17 days only, or not mated. All hoggets that were mated were scanned
      for pregnancy, using ultrasound, 48 days after the end of the breeding period,
      and identified as being either non-pregnant, or as singleton- or twin-bearing.
      RESULTS: Hoggets mated in the second 17-day period only were significantly
      lighter than those mated in either the first 17-day period only (p < 0.001), or
      in both the first and second 17-day periods (p < 0.02). At Day 1, twin-bearing
      hoggets were heavier than singleton-bearing hoggets (p < 0.001) and tended to be
      heavier (p = 0.06) than non-pregnant hoggets. At Day 18, twin-bearing hoggets
      were heavier than non-pregnant (p = 0.01) and singleton-bearing (p < 0.01)
      hoggets. A lesser proportion (p < 0.001) of unteased hoggets was mated in the
      first 17-day period only, compared to T17 hoggets. Conversely, a greater
      proportion of unteased hoggets was mated in the second 17-day period only,
      compared to either T8 (p < 0.01) or T17 (p < 0.001) hoggets. A lesser proportion
      of unteased hoggets was mated in the first 17 days of breeding, regardless of
      whether they returned to oestrus or not, in comparison to either T8 (p = 0.001)
      or T17 (p < 0.001) hoggets. Of those mated in the first 17 days of the breeding
      period, T8 hoggets were less likely (p < 0.05) to be mated in the first 5 days of
      that period but more likely to be mated in the last 7 days, compared to unteased
      and T17 hoggets. T17 hoggets had higher pregnancy rates to the first 17 days of
      breeding compared with either unteased (p = 0.01) or T8 hoggets (p = 0.06), and
      were more likely (p < 0.05) to be twin-bearing. In addition, the scanning
      percentage of T17 hoggets was higher than either unteased or T8 hoggets (p <
      0.05). CONCLUSIONS: Heavier hoggets at breeding are more likely to be mated
      during the first 17 days of breeding and to be twin-bearing. While teasing for
      just 8 days increased the numbers mated in the first 17 days of breeding it did
      not increase the numbers of hoggets pregnant to that period. In contrast, teasing
      for 17 days did increase the numbers pregnant to the first 17 days of breeding
      and also increased the overall scanning percentage. It is recommended that
      farmers use a 17-day period of teasing before the breeding of ewe hoggets.

PMID- 16596162
TI  - The effect of individual liveweight and condition of beef cows on their
      reproductive performance and birth and weaning weights of calves.
AB  - AIM: To examine of the influence of liveweight (LW), condition (CS) and age of
      dam on inter-calving interval (ICI), date of calving, days from joining to
      calving, and birth and weaning weights of calves. METHODS: LW and CS were
      measured in a herd of mixed-aged (3-8 years) Hereford x Friesian beef cows on
      four occasions, annually, over a 3-year period from joining (the date bulls were
      introduced into the herd at the start of a restricted breeding season) in
      November 2000 to weaning in March 2004. The four dates of weighing and condition
      scoring were joining (November), weaning (March), winter (June), and pre-calving
      (August). Calves were tagged, identified to their dam, and weighed within 24 h of
      birth, and at weaning. Date of calving, ICI and days from joining to calving were
      determined. RESULTS: The CS and LW of cows varied between years. LW increased in
      cows up to 6 years of age. Three-year-old cows had a longer ICI than older cows.
      Change in CS and LW from winter to pre-calving and pre-calving to joining were
      negatively correlated with ICI for younger cows but not for cows > or = 5 years
      (CS) and 6-8 years (LW) old. No difference in CS or LW precalving was evident
      between cows that subsequently became pregnant compared with non-pregnant cows,
      although cows that became pregnant gained more condition from pre-calving to
      joining than non-pregnant cows. Pregnant cows were heavier and had higher CS at
      joining than non-pregnant cows. CONCLUSIONS: Young cows, up to second-mating as 3
      year-olds, would benefit from separate nutritional management from older cows, to
      ensure ICI and days to conception are kept at targeted levels. In addition,
      increasing CS from pre-calving to joining and higher LW and CS at joining
      resulted in higher pregnancy rates.

PMID- 16596163
TI  - Increased life span due to calorie restriction in respiratory-deficient yeast.

PMID- 16596166
TI  - Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter
      DNA hypermethylation.
AB  - The class III histone deactylase (HDAC), SIRT1, has cancer relevance because it
      regulates lifespan in multiple organisms, down-regulates p53 function through
      deacetylation, and is linked to polycomb gene silencing in Drosophila. However,
      it has not been reported to mediate heterochromatin formation or heritable
      silencing for endogenous mammalian genes. Herein, we show that SIRT1 localizes to
      promoters of several aberrantly silenced tumor suppressor genes (TSGs) in which
      5' CpG islands are densely hypermethylated, but not to these same promoters in
      cell lines in which the promoters are not hypermethylated and the genes are
      expressed. Heretofore, only type I and II HDACs, through deactylation of lysines
      9 and 14 of histone H3 (H3-K9 and H3-K14, respectively), had been tied to the
      above TSG silencing. However, inhibition of these enzymes alone fails to re
      activate the genes unless DNA methylation is first inhibited. In contrast,
      inhibition of SIRT1 by pharmacologic, dominant negative, and siRNA (small
      interfering RNA)-mediated inhibition in breast and colon cancer cells causes
      increased H4-K16 and H3-K9 acetylation at endogenous promoters and gene re
      expression despite full retention of promoter DNA hypermethylation. Furthermore,
      SIRT1 inhibition affects key phenotypic aspects of cancer cells. We thus have
      identified a new component of epigenetic TSG silencing that may potentially link
      some epigenetic changes associated with aging with those found in cancer, and
      provide new directions for therapeutically targeting these important genes for re
      expression.

PMID- 16596165
TI  - The dictyostelium kinome--analysis of the protein kinases from a simple model
      organism.
AB  - Dictyostelium discoideum is a widely studied model organism with both unicellular
      and multicellular forms in its developmental cycle. The Dictyostelium genome
      encodes 285 predicted protein kinases, similar to the count of the much more
      advanced Drosophila. It contains members of most kinase classes shared by fungi
      and metazoans, as well as many previously thought to be metazoan specific,
      indicating that they have been secondarily lost from the fungal lineage. This
      includes the entire tyrosine kinase-like (TKL) group, which is expanded in
      Dictyostelium and includes several novel receptor kinases. Dictyostelium lacks
      tyrosine kinase group kinases, and most tyrosine phosphorylation appears to be
      mediated by TKL kinases. About half of Dictyostelium kinases occur in subfamilies
      not present in yeast or metazoa, suggesting that protein kinases have played key
      roles in the adaptation of Dictyostelium to its habitat. This study offers
      insights into kinase evolution and provides a focus for signaling analysis in
      this system.

PMID- 16596167
TI  - PRKCA and multiple sclerosis: association in two independent populations.
AB  - Multiple sclerosis (MS) is a chronic disease of the central nervous system
      responsible for a large portion of neurological disabilities in young adults.
      Similar to what occurs in numerous complex diseases, both unknown environmental
      factors and genetic predisposition are required to generate MS. We ascertained a
      set of 63 Finnish MS families, originating from a high-risk region of the
      country, to identify a susceptibility gene within the previously established 3.4
      Mb region on 17q24. Initial single nucleotide polymorphism (SNP)-based
      association implicated PRKCA (protein kinase C alpha) gene, and this association
      was replicated in an independent set of 148 Finnish MS families (p = 0.0004;
      remaining significant after correction for multiple testing). Further, a dense
      set of 211 SNPs evenly covering the PRKCA gene and the flanking regions was
      selected from the dbSNP database and analyzed in two large, independent MS
      cohorts: in 211 Finnish and 554 Canadian MS families. A multipoint SNP analysis
      indicated linkage to PRKCA and its telomeric flanking region in both populations,
      and SNP haplotype and genotype combination analyses revealed an allelic variant
      of PRKCA, which covers the region between introns 3 and 8, to be over-represented
      in Finnish MS cases (odds ratio = 1.34, 95% confidence interval 1.07-1.68). A
      second allelic variant, covering the same region of the PRKCA gene, showed
      somewhat stronger evidence for association in the Canadian families (odds ratio =
      1.64, 95% confidence interval 1.39-1.94). Initial functional relevance for
      disease predisposition was suggested by the expression analysis: The transcript
      levels of PRKCA showed correlation with the copy number of the Finnish and
      Canadian "risk" haplotypes in CD4-negative mononuclear cells of five Finnish
      multiplex families and in lymphoblast cell lines of 11 Centre d'Etude du
      Polymorphisme Humain (CEPH) individuals of European origin.

PMID- 16596169
TI  - Understanding the basis for Down syndrome phenotypes.
AB  - Down syndrome is a collection of features that are caused by trisomy for human
      Chromosome 21. While elevated transcript levels of the more than 350 genes on the
      chromosome are primarily responsible, it is likely that multiple genetic
      mechanisms underlie the numerous ways in which development and function diverge
      in individuals with trisomy 21 compared to euploid individuals. We consider
      genotype-phenotype interactions with the goal of producing working concepts that
      will be useful for approaches to ameliorate the effects of trisomy.

PMID- 16596168
TI  - Novel gene acquisition on carnivore Y chromosomes.
AB  - Despite its importance in harboring genes critical for spermatogenesis and male
      specific functions, the Y chromosome has been largely excluded as a priority in
      recent mammalian genome sequencing projects. Only the human and chimpanzee Y
      chromosomes have been well characterized at the sequence level. This is primarily
      due to the presumed low overall gene content and highly repetitive nature of the
      Y chromosome and the ensuing difficulties using a shotgun sequence approach for
      assembly. Here we used direct cDNA selection to isolate and evaluate the extent
      of novel Y chromosome gene acquisition in the genome of the domestic cat, a
      species from a different mammalian superorder than human, chimpanzee, and mouse
      (currently being sequenced). We discovered four novel Y chromosome genes that do
      not have functional copies in the finished human male-specific region of the Y or
      on other mammalian Y chromosomes explored thus far. Two genes are derived from
      putative autosomal progenitors, and the other two have X chromosome homologs from
      different evolutionary strata. All four genes were shown to be multicopy and
      expressed predominantly or exclusively in testes, suggesting that their
      duplication and specialization for testis function were selected for because they
      enhance spermatogenesis. Two of these genes have testis-expressed, Y-borne copies
      in the dog genome as well. The absence of the four newly described genes on other
      characterized mammalian Y chromosomes demonstrates the gene novelty on this
      chromosome between mammalian orders, suggesting it harbors many lineage-specific
      genes that may go undetected by traditional comparative genomic approaches.
      Specific plans to identify the male-specific genes encoded in the Y chromosome of
      mammals should be a priority.

PMID- 16596170
TI  - Analysis of connective tissue progenitor cell behavior on polydimethylsiloxane
      smooth and channel micro-textures.
AB  - Growth of human connective tissue progenitor cells (CTPs) was characterized on
      smooth and microtextured polydimethylsiloxane (PDMS) surfaces. Human bone marrow
      derived cells were cultured for nine days under conditions promoting osteoblastic
      differentiation on Smooth PDMS and PDMS Channel microtextures (11 microm high, 45
      microm wide channels, and separated by 5 microm wide ridges). Glass tissue
      culture dish surfaces were used as controls. Cell numbers per colony, cell
      density within colonies, alignment of cells, area of colonies, and colony shapes
      were determined as a function of substrate surface topography. An alkaline
      phosphatase stain was used as a marker for osteoblastic phenotype. CTPs attached,
      proliferated, and differentiated on all surfaces with cell process lengths of up
      to 80 microm. Cells on the Smooth PDMS and control surfaces spread and
      proliferated as colonies in proximity to other cells and migrated in random
      directions creating colonies that covered significantly larger areas (0.96 and
      1.05 mm(2), respectively) than colonies formed on PDMS Channel textures (0.64
      mm(2)). In contrast, cells on PDMS Channel textures spread, proliferated, aligned
      along the channel axis, and created colonies that were more dense, and with
      lengths of longest colony axes that were significantly longer (3252 microm) than
      those on the Smooth PDMS (1265 microm) and control surfaces (1319 microm). Cells
      on PDMS Channel textures were aligned at an angle of 14.44 degrees relative to
      the channel axis, and the resulting colonies exhibited a significantly higher
      aspect ratio (13.72) compared to Smooth PDMS (1.57) and control surfaces (1.51).

PMID- 16596171
TI  - The expression of vascular endothelial growth factor determines the efficacy of
      post-operative adjuvant chemotherapy using oral fluoropyrimidines in stage II or
      III colorectal cancer.
AB  - The aim of this study was to determine any correlation between the efficacy of
      post-operative adjuvant chemotherapy using oral fluoropyrimidines and the
      vascular endothelial growth factor (VEGF) expression in primary colorectal cancer
      tissues. The data were reviewed retrospectively on 342 patients with colorectal
      cancer at stage II or III, who underwent potentially curative resection between
      1988 and 1998. Of these, 225 received post-operative administration of oral
      fluoropyrimidines such as UFT and 5'-DFUR, while the other 117 patients underwent
      surgery alone. Immunostaining for VEGF was performed using colorectal tumours.
      Overall, VEGF was positively expressed in primary tumour cells in 48% of
      patients. The disease-free survival rate and the overall survival rate in the
      chemotherapy group were higher than those in the surgery-alone group, although
      not significantly. However, the disease-free survival rate and the overall
      survival rate were similar between the two groups in patients with a tumour
      positive for VEGF. Multivariate analysis revealed that the VEGF expression was an
      independent factor for post-operative recurrence, and the VEGF expression and
      post-operative adjuvant chemotherapy were an independent factor for overall
      survival, in addition to the lymph node metastasis and the venous invasion. In
      conclusion, the efficacy of post-operative adjuvant chemotherapy using oral
      fluoropyrimidines may not be as great for patients with a tumour positive for
      VEGF having a greater risk of post-operative recurrence. The results support
      further investigation on efficacy of molecular targeting therapy for VEGF in
      combination with oral fluoropyrimidines as post-operative adjuvant therapy in
      colorectal cancer positive for VEGF.

PMID- 16596172
TI  - Anti-apoptotic N-cadherin signaling and its prognostic implication in human
      hepatocellular carcinomas.
AB  - N-cadherin signaling has recently been implicated in the progression of certain
      epithelial tumors by promoting invasion and dissemination of cancer cells. N
      cadherin has also been reported to exert an anti-apoptotic effect. In this study,
      we attempted to evaluate the participation of this adhesion molecule in the
      progression of human hepatocellular carcinomas (HCCs) by analyzing its anti
      apoptotic signaling as well as its prognostic implication in HCC patients. N
      cadherin was found to be expressed in human HCCs. We established a stable human
      HCC cell line expressing a truncated N-cadherin, NCaddeltaC, with a dominant
      negative action. NCaddeltaC-expressing cells were more susceptible to bile acid
      induced apoptosis than control cells. N-cadherin was found to complex with
      procaspase-8, and this association was diminished in NCaddeltaC-expressing cells,
      leading to enhanced procaspase-8 recruitment to death-inducing signaling complex
      following bile acid treatment. A clinicopathological analysis in patients who had
      undergone surgical resection for HCC revealed that tumoral N-cadherin up
      regulation was significantly related to poor recurrence-free and overall
      survival. Our findings implicate N-cadherin signaling as contributing to HCC
      progression by exerting anti-apoptotic effects. Thus, we suggest that the
      selective interruption of this signaling may have therapeutic potential.

PMID- 16596173
TI  - E-cadherin and DAP kinase in pancreatic adenocarcinoma and corresponding lymph
      node metastases.
AB  - E-cadherin and DAP kinase have been implicated as 'invasion suppressor' genes in
      human cancer. The aim of this study was to analyze the methylation status of E
      cadherin and DAP kinase and the expression of the protein in the metastatic
      lesions and to compare it with the expression in the primary tumor. Methylation
      specific PCR of the DAP kinase and E-cadherin promoter was performed in 28
      primary adenocarcinomas of the pancreas and in 13 corresponding regional lymph
      node metastases. The presence of E-cadherin and DAP kinase protein was assessed
      by immunohistochemistry. Metastatic lymph nodes showed a significant different
      expression profile from the primary tumor. E-cadherin methylation was observed in
      8/28 (29%) and loss of protein expression was observed in 16/28 (57%) of
      pancreatic carcinomas. E-cadherin methylation was observed in 7/13 (54%) and loss
      of protein expression was observed in 11/13 (85%) lymph node metastases
      (p=0.047). DAP kinase methylation occurred in 11/28 (39%) pancreatic carcinomas
      and loss of protein expression was observed in 13/28 (46%). DAP kinase was
      methylated in 6/13 (46%) lymph node meta-stases and loss of protein expression
      was observed in 10/13 (77%) (p=0.039). Comparing primary tumor and corresponding
      lymph node metastases in 13 cases, the status of E-cadherin methylation was
      discordant in 2 cases. The protein expression pattern of E-cadherin and DAP
      kinase was discordant in 4 and 3 cases respectively. Unmethylated tumor samples
      did not express E-cadherin in 12 and DAP kinase protein in 6 cases. Our results
      demonstrate that reduction of E-cadherin and DAP kinase expression is more
      frequent in lymph node metastases than in the primary tumor and methylation of
      the promoter region contributes to this reduction; however, an alternative
      mechanism of inactivation seems to exist.

PMID- 16596174
TI  - Anti-tumor effects of herbal medicines on endometrial carcinomas via estrogen
      receptor-alpha-related mechanism.
AB  - This study was performed to examine the relationship between the anti-tumor
      effects of herbal medicine and endometrial carcinoma with ER-related mechanisms.
      An endometrial cancer cell line (Ishikawa) was used for this study. The cell
      viability and expression of estrogen receptors (ER) were determined by MTT and RT
      PCR. A dose-dependent decrease of viability and apoptosis of the cancer cells was
      generated by exposure to the herbal medicines, Juzen-taiho-to or Shimotsu-to. The
      expression of ER-alpha mRNA, but not ER-beta mRNA was suppressed by Juzen-taiho
      to or Shimotsu-to in an endometrial cancer cell line. The anti-tumor effect of
      these herbal medicines against endometrial carcinoma might be correlated to the
      ER-alpha related mechanism.

PMID- 16596175
TI  - Glucocorticosteroid receptors in ovarian carcinomas.
AB  - The use of glucocorticoids (GCs) in oncology, including in the treatment of
      ovarian carcinomas, is controversial. In vitro experiments suggest that GCs
      negatively influence the response to chemotherapy, but the few available clinical
      data show only benefits. Glucocorticoid action is mediated via glucocorticoid
      receptors (GRs). This study aims to define any clinical implications of GR
      expression in ovarian cancer to further the debate. Archived tissue samples from
      patients with histologically confirmed ovarian cancer were analyzed for GR
      expression and evaluated by immunohistochemistry and immunoreactive score. The
      results were related to the patients' overall survival. Kaplan-Meier survival and
      residual survival analyses gave no evidence that GR expression had any prognostic
      value in the 85 cases studied. No evidence of poorer survival was found in a
      small subset of GR-positive patients who received GC treatment. Glucocorticoid
      receptor expression had no prognostic impact in our study. However, GC (cortisol)
      is being produced continuously by the body, which may have stimulated GR-positive
      ovarian cancer cells. Our finding does not exclude the possibility that long-term
      GC treatment has adverse effects, and it should also be emphasized that treatment
      duration, dosage and dosing regimens, as well as the choice of an appropriate GC
      and the mode of application, determine the risks and benefits. Our study showed
      no evidence against using GC for antiemetic prophylaxis in ovarian carcinomas.

PMID- 16596176
TI  - Recurrent NMYC copy number gain and high protein expression in basal cell
      carcinoma.
AB  - Formation of basal cell carcinoma (BCC) has been linked to deregulation in the
      sonic hedgehogh (Shh) signalling pathway. Though mutations of the genes, PTCH1
      and SMO, are known to be involved in aberrant Shh signalling, the distinct
      downstream effectors of these genes are poorly described. Studies have indicated
      that the NMYC oncogene is a potential Shh downstream effector. To assess the
      expression of Nmyc protein and gene copy numbers of the NMYC gene locus in a
      representative BCC tumour collection, immunohistochemistry (IHC) and fluorescence
      in situ hybridisation (FISH) were performed on 273 BCC specimens of different
      growth patterns and anatomic localisations on tissue microarray (TMA) sections.
      High Nmyc protein expression was detected in 72.7% (160/220) of all BCC
      specimens. Strong Nmyc immunopositivity was more frequently found in infiltrative
      BCCs compared to nodular/superficial BCCs (p=0.005), and in BCCs of the head
      compared to BCCs of other anatomic localisations (p=0.021). The prevalence of
      NMYC copy number gains was 17.5% (37/211), including three tumours with nodular
      differentiation that exhibited a distinct high-level amplification of the NMYC
      locus. These data indicate that high expression of the Shh downstream mediator,
      Nmyc, is a frequent event in BCC, predominantly in more aggressive subtypes.
      Although the NMYC copy number gain found in a subset of cases might contribute to
      this aberrant Nmyc protein expression by a gene dosage effect, our data suggests
      that Nmyc protein can also be induced by aberrant Shh signalling, acting as an
      effector molecule of the Shh pathway. Novel systemic anti-sense NMYC inhibition
      strategies could be a promising option for therapy-refractory BCC.

PMID- 16596177
TI  - The effect of RhoA on human umbilical vein endothelial cell migration and
      angiogenesis in vitro.
AB  - The mechanisms that control the morphologic organization of endothelial cells
      (ECs) into new blood vessels are not well understood. Recent studies revealed
      that the small G proteins of the Rho family are key regulators of cell migration,
      involving reorganization of the actin cytoskeleton, cell migration and the
      regulation of gene transcription. We hypothesized that RhoA GTPase, a member of
      the Rho family, may play an important role in EC organization during
      angiogenesis, the process of new vessel formation in pre-existing tissues. To
      test this hypothesis, we investigated the effects of RhoA on human umbilical vein
      endothelial (HUVE) cell migration and angiogenesis in vitro, by stably
      transfecting HUVE cells with sense RhoA expression plasmid through the Lipofect
      2000 system. Wound assay in vitro and 3-dimensional cell culture were used to
      detect the migration and angiogenesis capacity of HUVE cells. The morphological
      changes of transfected cells were revealed under confocal and phase contrast
      microscopy. Our results demonstrated that the increased expression of RhoA in
      HUVE cells significantly enhanced the morphogenetic changes and cytoskeletal
      reorganization of the transfected cells, and also enhanced cell migration and
      angiogenic capacity in vitro, suggesting that RhoA plays an important role in the
      process of HUVE cell migration and angiogenesis in vitro.

PMID- 16596178
TI  - A new tool for experimental tumour research.
AB  - Surgical resected tumours are often stored for hours in the clinic upon transfer
      to the bench leading to apoptosis of tumour cells making them no longer suitable
      for molecular analysis and diagnostic procedures. The way out of this problem may
      be a new oxygen-enriched solution (OES). We tested this agent using surgical
      resections of carcinomas of lung, rectum and pancreas. Immediately after
      resection, one part of each individual tumour was stored in PBS and the other
      part in OES, and the content of viable or dead cells was determined by trypan
      blue exclusion and MTT-assay. We found that OES keeps tumour cells up to 3 days
      and longer more viable than PBS and reduces the percentage of dead cells without
      inducing therapy resistance and affecting the outcome of experimental procedures.
      Thus, storing freshly resected tumours in OES may save time for tumour transfer
      and initiation of experiments.

PMID- 16596179
TI  - Expression of gastric mucin MUC5AC and gastric transcription factor SOX2 in
      ampulla of vater adenocarcinoma: comparison between expression patterns and
      histologic subtypes.
AB  - The purpose of this study was to examine the expression pattern of MUC5AC and
      SOX2 in ampulla of vater adenocarcinoma and evaluate the association between
      expression of these gastric epithelial markers and the histologic phenotype of
      ampulla of vater carcinoma. Six surgically resected samples of ampulla of vater
      adenocarcinoma, including four intestinal type carcinomas and two
      pancreatobiliary type carcinomas, were studied. We performed immunohistochemistry
      with a monoclonal antibody against MUC5AC and a polyclonal anti-SOX2 antibody. In
      two of the four intestinal type carcinomas, MUC5AC and SOX2 were focally
      expressed in the superficial neoplastic mucosa. However, in the centre of the
      tumour and in other invasive lesions, including vascular invasive lesions and
      metastatic lymph nodes, neither MUC5AC nor SOX2 was expressed. In contrast, in
      both pancreatobiliary type carcinomas, expression of MUC5AC and SOX2 was
      maintained or increased in invasive lesions. Our immunohistochemistry data
      suggest that MUC5AC and SOX2 are associated with the pancreatobiliary phenotype
      of ampulla of vater carcinoma and involved in later events in carcinogenesis,
      such as invasion and metastasis.

PMID- 16596180
TI  - Antiangiogenic agent, thalidomide increases the antitumor effect of single high
      dose irradiation (gamma knife radiosurgery) in the rat orthotopic glioma model.
AB  - Gliomas are primary brain tumors associated with a poor prognosis partly due to
      resistance to conventional therapies. To overcome this problem, we investigated
      the combined effects of gamma knife radiosurgery (GKS) and an antiangiogenic
      agent, thalidomide (THD), or a chemotherapeutic agent, temozolomide (TMZ), on a
      rat glioma model. GKS (20 Gy single dose) alone and/or drugs (for 3 days) were
      delivered 14 or 18 days after stereotactic implantation of C6/LacZ glioma cells
      into the brains of Sprague-Dawley rats. A group of animals treated with or
      without drugs for 3 days was irradiated on day 18 and sacrificed at 24 h after
      GKS to evaluate cell proliferation, apoptosis and microvessel density. The other
      group of animals was irradiated on day 14 and sacrificed at day 5 after GKS for
      the measurement of tumor volume. Apoptosis of endothelial cells in the tumor beds
      was only observed in the early period after GKS. Decreased cell proliferation and
      increased tumor cell apoptosis were observed in rat gliomas treated with GKS and
      THD or TMZ. The combination treatments with GKS and THD or GKS and TMZ also
      decreased microvessel density, i.e. angiogenesis, more effectively compared with
      GKS treatment alone. The combination of GKS and THD was the most effective
      regimen, resulting in a significant decrease of tumor volume. We suggest that the
      antitumor effect of GKS on glioma is enhanced by the addition of THD. Therefore,
      combined therapy with GKS and THD might be a favorable treatment for gliomas.

PMID- 16596181
TI  - Preventive effects of chrysin on the development of azoxymethane-induced colonic
      aberrant crypt foci in rats.
AB  - The modifying effects of dietary feeding with chrysin (5,7-dihydroxyflavone) on
      the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF)
      were investigated in male F344 rats. We also assessed the effect of chrysin on
      mitosis and apoptosis in 'normal appearing' crypts. To induce ACF, rats were
      given two weekly subcutaneous injections of AOM (20 mg/kg body weight). They also
      received an experimental diet containing chrysin (0.001 or 0.01%) for 4 weeks,
      starting 1 week before the first dose of AOM. AOM exposure produced a substantial
      number of ACF (73+/-13/rat) at the end of the study (week 4). Dietary
      administration of chrysin caused significant reduction in the frequency of ACF:
      0.001% chrysin, 37+/-17/rat (49% reduction, P<0.001); and 0.01% chrysin, 40+/
      10/rat (45% reduction, P<0.001). In addition, chrysin administration
      significantly reduced the mitotic index and significantly increased the apoptotic
      index in 'normal appearing' crypts. These findings might suggest a possible
      chemopreventive activity of chrysin in the early step of colon tumorigenesis
      through modulation of cryptal cell proliferation activity and apoptosis.

PMID- 16596182
TI  - Cellular components involved in the cell death induced by cisplatin in the
      absence of p53 activation.
AB  - Cisplatin (CDDP) is a DNA damaging agent and is widely used for treating cancer.
      While the role of p53 in CDDP-induced cell death has been stressed, evidence
      exists that CDDP can also kill p53-mutated cells. To investigate the latter
      mechanism, we performed a comparative study using three different human cell
      types, SNU-16 (a stomach cancer cell-line), U937 (a leukemic cell-line) and 293T
      (a kidney fibroblast cell-line), which are defective in terms of p53 activation.
      A focus was placed on Bcl-2 family proteins, reactive oxygen species (ROS), and
      mitogen-activated protein kinases. Our results suggest that the ability of CDDP
      to kill these cells can be mediated by JNK, p38 MAPK and ROS, but not by ERK. It
      was also found that CDDP can increase the ratio of pro-apoptotic/pro-survival Bcl
      2 members. While the importance of these components was found to depend on cell
      type, JNK was commonly involved in the deaths of all cell types examined.
      Therefore, the JNK pathway appears to be an ideal target for the modulation of
      the lethal action of CDDP in multiple types of p53-mutated cells.

PMID- 16596183
TI  - Expression profile of N-cadherin differs from other classical cadherins as a
      prognostic marker in renal cell carcinoma.
AB  - Renal cell carcinomas (RCCs) primarily express cadherin-6 and N-cadherin rather
      than E-cadherin, and the aberrant expression of cadherin-6 correlates with a poor
      prognosis in patients with E-cadherin-absent RCC. However, the role of N-cadherin
      in RCC has not yet been elucidated. In this study, we analyze the expression
      pattern of N-cadherin in surgical RCC specimens and discuss the function of N
      cadherin in RCC together with a re-evaluation of our previous study. Forty-six
      surgically resected RCC specimens were used in this study. The expression and
      localization of E-cadherin and N-cadherin in surgical specimens were demonstrated
      by immunohistochemistry. Correlations between the expression pattern of each
      cadherin, pathological parameters and patient survival were analyzed. RCC
      specimens expressed N-cadherin as a normal pattern despite the elevation of tumor
      grade, and patients with N-cadherin-normal RCC had a poorer prognosis than those
      with N-cadherin-abnormal RCC. Since our previous study showed that N-cadherin
      only functioned in cell attachment when E-cadherin and cadherin-6 were impaired,
      N-cadherin plays a different role from E-cadherin or cadherin-6 in RCC and may be
      associated with the aggressiveness and malignant potential of RCC.

PMID- 16596184
TI  - Long-term survival and tumor 5-FU sensitivity in patients with stage IV
      colorectal cancer and peritoneal dissemination.
AB  - Among 125 patients with peritoneal dissemination (P1-3) of colorectal cancer,
      including those with other synchronous metastases, the 5-year overall survival
      (OS) rate was 13.3% for P1 patients (n=30), 12.8% for P2 patients (n=39), and
      1.8% for P3 patients (n=56) (P1 vs. P2, p=N.S.; P2 vs. P3, p=0.02; P1 vs. P3,
      p=0.001), while the median survival time (MST) was 12.0, 14.1, and 3.1 months,
      respectively. The 5-year OS rates for patients who had peritoneal dissemination
      without other metastases were 17.6% (n=17), 12.5% (n=19), and 3.4% (n=28) (P1 vs.
      P2, p=N.S.; P2 vs. P3, p=N.S.; P1 vs. P3, p=0.039), while the MST was 25.1, 15.1,
      and 12.5 months, respectively. In the P3 short survival group (SSG; n=13), TS
      expression was high in 7.7% (1/13) and low in 92.3% (12/13) of tumors, while DPD
      expression was high in 38.5% (5/13) and low in 61.5% (8/13) of tumors. In the P3
      long survival group (LSG; n=15), the corresponding values were 80.0% (12/15),
      20.0% (3/15), 33.3% (5/15), and 66.7% (10/15). High TS and low DPD expression was
      found in only 7.7% (1/13) of the SSG tumors vs. 46.7% (7/15) of the LSG tumors
      (p=0.028). These results suggest that the prognosis of stage IV colorectal cancer
      with P3 peritoneal dissemination is extremely poor. In addition, patients fitting
      the SSG criteria are unlikely to respond to treatment with 5-FU+LV, and may need
      combination chemotherapy using CPT-11 and/or L-OHP.

PMID- 16596185
TI  - The regulatory effect of tamoxifen on fibronectin expression in estrogen
      dependent MCF-7 breast carcinoma cells.
AB  - We investigated the regulatory effect of tamoxifen (TAM) on fibronectin (FN)
      expression in estrogen-dependent MCF-7 breast carcinoma cells both in vitro and
      in vivo. in vitro, MCF-7 cells were cultured with 17beta-estradiol (E2) and/or
      TAM. In the animal experiment in vivo, MCF-7 tumors were grown in ovariectomized
      athymic mice by implanting a sustained release E2 pellet. The E2 pellets were
      removed after 3 weeks of E2 treatment. Animals were then divided into four
      groups: 1) an E2 (0.72 mg/pellet) pellet [E2(+)]; 2) an E2 and a TAM (5
      mg/pellet) pellet [E2(+)TAM]; 3) no treatment [E2(-)] and 4) a TAM pellet [E2(
      )TAM]. Following each treatment for 4 weeks, all animals were sacrificed and
      tumors were removed. Specimens, cells (in vitro) or tumors (in vivo), were
      homogenized and assayed for FN by Western blots. In the in vitro experiment, FN
      expression in MCF-7 cells decreased by incubating with 10(-9) M E2 and increased
      with 10(-6) M TAM. The effect of TAM increasing FN expression was inhibited by
      incubation accompanied with 10(-9) M E2 or 1 microg/ml transforming growth factor
      beta (TGF-beta) neutralizing antibody. In the in vivo animal experiment FN
      expression in the tumors of E2(+) mice was lower than that of E2(-) mice.
      However, TAM increased FN expression in the tumors regardless of E2 pellet. These
      results suggest that TAM increases FN expression of MCF-7 breast carcinoma cells
      and that these regulatory effects of TAM on FN expression are partly mediated by
      TAM-induced TGF-beta.

PMID- 16596186
TI  - Expression of CD137 and CD137 ligand in colorectal cancer patients.
AB  - The cytokine CD137, a member of the TNF receptor family, is expressed by T cells
      and regulates activation and proliferation of these cells. The CD137 ligand
      (CD137L) is expressed by antigen-presenting cells including macrophages, but also
      on various carcinoma cells. CD137/CD137L interaction plays a central role in
      sustaining T cell and macrophage activation, i.e. in antitumour immunity. The
      present study was designed to investigate whether CD137 and CD137L protein levels
      are altered in colorectal tumours compared with paired normal tissues. The CD137
      and CD137L plasma levels from patients with colorectal cancer were also examined.
      Collectively, we noted a significantly lower CD137L level in cancerous tissue
      compared with paired normal tissue, and the difference in CD137L protein level
      was significantly lower in the colon cancer subgroup compared with paired normal
      colon tissue. On the other hand, we found an elevated CD137 protein level in the
      rectal cancer subgroup compared with paired normal rectal tissue. Patients with a
      tumour localised in the colon revealed significantly higher soluble CD137 protein
      concentration in the plasma than patients with a tumour localised in the rectum,
      and there was a tendency toward a higher concentration of CD137L protein in the
      plasma from patients with tumour localised in the colon. Moreover, the plasma
      concentrations of CD137 and CD137L proteins were strongly and significantly
      correlated. The different expression levels of CD137 and CD137L in the colon and
      rectum may reflect divergent mechanisms involved in the pathogenesis of
      colorectal cancer and lead to dissimilar protective immunity.

PMID- 16596187
TI  - Liposomal cisplatin combined with gemcitabine in pretreated advanced pancreatic
      cancer patients: a phase I-II study.
AB  - The present trial is a phase I-II study based on a new liposomal cisplatin
      (lipoplatin). Previous preclinical and clinical data (phase I pharmacokinetics)
      led to the investigation of a combined treatment modality involving lipoplatin
      and gemcitabine. The gemcitabine dose was kept standard at 1000 mg/m2 and the
      lipoplatin dose was escalated from 25 mg/m2 to 125 mg/m2. The treatment was
      administered to advanced pretreated pancreatic cancer patients who were
      refractory to previous chemotherapy which included gemcitabine. Lipoplatin at 125
      mg/m2 was defined as dose limiting toxicity (DLT) and 100 mg/m2 as the maximum
      tolerated dose (MTD) in combination with 1000 mg/m2 of gemcitabine. Preliminary
      objective response rate data showed a partial response in 2/24 patients (8.3%),
      disease stability in 14 patients (58.3%) for a median duration of 3 months (range
      2-7 months) and clinical benefit in 8 patients (33.3%). Liposomal cisplatin is a
      non-toxic alternative agent to bare cisplatin. In combination with gemcitabine,
      it has an MTD of 100 mg/m2 and shows promising efficacy in refractory pancreatic
      cancer.

PMID- 16596188
TI  - Mutations of the epidermal growth factor receptor gene in gastrointestinal tract
      tumor cell lines.
AB  - The epidermal growth factor receptor (EGFR) is commonly overexpressed in many
      human tumors including gastrointestinal tract tumors. Gefitinib is a selective
      inhibitor of EGFR tyrosine kinase, and blocks several signal transduction
      pathways including those involved in tumor cell proliferation, angiogenesis and
      metastasis. Recent mutational and biological studies have suggested that
      mutations in the tyrosine kinase domain of the EGFR gene are well correlated with
      the response to gefitinib, and that these mutations are frequently observed in
      non-small cell lung cancers affecting women, East Asians and non-smokers. This
      led us to speculate that EGFR gene mutations may occur frequently in
      gastrointestinal tract carcinomas (GITCs) because overexpression is observed in
      these tumor types. To investigate EGFR mutations in GICTs, we studied 11
      esophageal, 6 gastric, and 12 colorectal cancer cell lines. We found a missense
      mutation in a gastric cancer cell line, and 10 single nucleotide polymorphisms.
      The occurrence of rare mutations in the tyrosine kinase domain of the EGFR gene
      suggests that gefitinib is unlikely to be reliable as single-drug therapy for
      GITCs.

PMID- 16596189
TI  - Construction and characterization of a novel fusion protein consisting of anti
      CD3 antibody fused to recombinant interleukin-2.
AB  - T cells can be activated in vitro by monoclonal antibodies to CD3 (anti-CD3) to
      become non-MHC restricted killer cells (CD3-AK). Anti-CD3 activation upregulates
      the expression of the interleukin (IL)-2 receptors on T cells whose expansion is
      facilitated by IL-2. The therapeutic effect of in vivo administration of anti-CD3
      and IL-2 has been investigated in many types of human cancers. To circumvent the
      toxicities posed by systemic administration of high-dose IL-2, there is interest
      in forming a strategy for targeting and concentrating IL-2 at the site where it
      is needed. This study investigates the feasibility of constructing a novel fusion
      protein consisting of IL-2 fused to the constant region of anti-CD3 antibody. Our
      results indicate that the specific IL-2 receptor-binding capability and
      bioactivity of the IL-2 portion as well as the CD3-binding and biological
      functions of anti-CD3 portion remain intact in this anti-CD3/IL-2 fusion protein.
      Thus, cytokines fused to anti-CD3 antibody by genetic engineering is feasible and
      may provide a new class of immunotherapeutics for cancer.

PMID- 16596190
TI  - Possible predictive markers related to micro-metastasis in breast cancer
      patients.
AB  - Despite significant advances in micro-metastasis detection methods, little is
      known about the relationship between micro-metastasis and primary tumors. The
      purpose of this study was to assess the ability of expression of the breast
      cancer-related markers, HER-2/neu, COX-2, VEGF and PDGF-B, as a predictor for
      micro-metastasis. As destination sites for micro-metastasis, we examined the
      peripheral blood (BD), bone marrow (BM) and sentinel lymph node (SLN) from 53
      breast cancer patients. Protein and gene expression of the markers at the primary
      site were determined by immunohistochemistry (IHC) and quantitative RT-PCR. BD
      and BM samples were processed using magnetic-activated cell separation and
      immunocytochemistry. SLNs were examined by hematoxylin and eosin (H&E) staining
      and IHC. The percentages of patients with micro-metastasis were 24.5% in BD,
      56.6% in BM, 26.4% in SLN by H&E and 41.5% in SLN by IHC. COX-2 gene
      amplification was significantly associated with SLN micro-metastasis by H&E
      (P=0.03). Overexpression of HER-2/neu predicts the presence of SLN micro
      metastasis as detected by H&E (P=0.005) and COX-2 overexpression predicts the
      presence of micro-metastasis in BM (P=0.005) and SLN by H&E (P<0.001) and IHC
      (P<0.001). Similarly, PDGF-B overexpression predicts micro-metastasis in BD
      (P=0.002), BM (P=0.003) and SLN by H&E (P=0.017), whereas VEGF overexpression
      predicts only the presence of SLN micro-metastasis by IHC (P=0.001). Our results
      indicate the possible value of using these markers to predict the risk of micro
      metastasis in breast cancer.

PMID- 16596191
TI  - Induction of G2/M arrest and inhibition of cyclooxygenase-2 activity by curcumin
      in human bladder cancer T24 cells.
AB  - Curcumin, a polyphenol compound derived from Curcuma longa Linn, has been
      recognized as a promising anti-cancer drug due to its multiple properties
      including anti-inflammatory, anti-oxidant and anti-carcinogenic activities. To
      elucidate the mechanisms by which curcumin inhibits human bladder carcinoma T24
      cell proliferation, we tested the effects of curcumin on specific cell cycle
      pathways and on the expression of cyclooxygenases (COXs). Curcumin inhibited the
      growth of T24 cells and induced G2/M arrest in a concentration-dependent manner,
      effects associated with the down-regulation of cyclin A and up-regulation of
      cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1). However, other G2/M
      regulatory molecules, such as cyclin A, Cdc2, Cdk2, Wee1 and Cdc25C, were not
      modulated by curcumin treatment. Furthermore, curcumin decreased the levels of
      COX-2 mRNA and protein expression without significant changes in the levels of
      COX-1, which correlated with a decrease in prostaglandin E2 (PGE2) synthesis.
      These observations suggest that curcumin may have therapeutic potential for
      bladder cancer patients.

PMID- 16596192
TI  - High rate of molecular alteration in histologically tumour-free bronchial
      epithelium of NSCLC patients detected by multicolour fluorescence in situ
      hybridisation.
AB  - Detection of molecular abnormalities could provide an essential tool for the
      diagnosis of non-small cell lung cancer (NSCLC) and defining patients at risk for
      early relapse. Fluorescence in situ hybridisation (FISH) targeting 17 gene loci
      was applied to determine the frequency of molecular alteration in NSCLC probes
      and adjacent tumour-free bronchial epithelium. FISH was performed on fresh frozen
      specimens from 76 patients with histologically confirmed NSCLC and 54 specimens
      of adjacent tumour-free tissue. Routine autopsy lung tissue probes from 7 cancer
      free patients served as a control group. Locus-specific (3p14.2, 3p21.2, 3p21.3,
      3p25.3, 5p15.2, 7p12, 8q24.12, 9p21, 13q14, and 17p13.1) as well as centromere
      probes (4, 6, 7, 9, 11 and 16) were used. Molecular alterations using FISH on
      interphase nuclei were detected in 100% of NSCLC tumour specimens and 89% of
      microscopically tumour-free tissues of NSCLC patients. In histologically 'normal'
      epithelium, the most frequent alterations were seen with locus-specific probes
      for 3p14.2, 3p.21, 3p21.3, 3p25.3 and 7p12 and centromere-specific probes 11 and
      16 (12-93%). As expected, the majority of genetic alterations seen in
      'premalignant' specimens were found in the correlating tumour probes. None of the
      tested parameters revealed prognostic significance in univariate Cox analysis.
      FISH analysis, performing multicolour strategies, demonstrated its power in
      detecting genetic abnormalities in NSCLC specimens and even in tumour-free
      sections of tumour patients.

PMID- 16596193
TI  - DNA cytosine methylation profile in various cancer-related genes is altered in
      cultured rat hepatocyte cell lines as compared with primary hepatocytes.
AB  - We determined the DNA cytosine methylation status in the promoter CpG islands of
      eight cancer-related genes (p16, Socs-1, Rassf1A, Hic-1, Dlc-1, Timp-1, Timp-2,
      and Timp-3) in five rat hepatocyte cell lines, including normal cell lines (Clone
      9 and CWSV-1) and tumor cell lines (H4-II-E-C3, MH1C1, and McA-RH7777). The
      experimental methods used to assess the methylation profile were methylation
      specific PCR (MSP) and methylation-sensitive digestion combined with PCR. The
      results were compared with the methylation status of rat primary hepatocytes. To
      evaluate methylation-mediated gene induction/silencing, the expression of gene
      transcripts was semi-quantitatively assessed using RT-PCR. In primary cells, the
      CpG islands of all genes tested were unmethylated. In contrast, there was at
      least one hypermethylated gene in the cultured cell lines. Three genes (p16, Socs
      1 and Rassf1A) were hypermethylated in Clone 9 cells; among the other five genes,
      three genes (Hic-1, Timp-1 and Timp-3) were hypermethylated in the CWSV-1 cell
      lines and two genes (Dlc-1 and Timp-2) were hypermethylated only in the tumor
      cell lines. The methylation status in some of the tested genes was altered at an
      early stage of cell culture as compared to primary cells. It is also noteworthy
      that hypermethylation in Socs-1, Rassf1, Hic-1, and Timp-3 was widespread among
      the cell lines tested, but not in the primary cells and Clone 9 cells. This study
      suggests that a cautious approach is required when cell lines are utilized to
      study methylation-related carcinogenic, metastatic or tumoricidal mechanisms.

PMID- 16596194
TI  - Differential expression of alternatively spliced mRNA forms of the insulin-like
      growth factor 1 receptor in human neuroendocrine tumors.
AB  - The activation of the insulin-like growth factor 1/IGF1 receptor system
      (IGF1/IGF1R) is a critical event in the transformation and tumorigenicity
      processes in a wide variety of human tumors. The IGF1/IGF1R system has been
      recently studied in carcinoid tumors that often arise in the gastrointestinal
      tract; these tumors are characterized by hypersecretion of bioamines and
      neuropeptides, leading to functional tumor disease. Two alternatively spliced
      IGF1R mRNA transcripts have been described to differ by only three nucleotides
      (CAG) in the coding sequence, resulting in an amino-acid change from the
      originally described Thr-Gly to an Arg in the extracellular portion of the
      receptor beta subunit. In transfected Chinese hamster ovary cells, the form
      without CAG (CAG-) exhibited an approximate 2-fold increase in IGF1 stimulation
      of activities required for its mitogenic properties. In this study, we examine
      the relative expression of the two IGF1R mRNA isoforms by a semiquantitative RT
      PCR approach using highly standardized conditions, beta-2 microglobulin (B2M) as
      a reference gene and gel imaging analysis. We analyzed a large series of human
      neuroendocrine tumors (32 samples) and 9 normal tissues. A significant higher
      expression of both isoforms in the tumor samples (approximately 2-fold increase)
      was found, while a constant CAG+/CAG- IGF1R mRNA isoforms of an approximate 3:1
      ratio was observed in all tumoral and normal cell types studied. The phylogenetic
      study of the IGF1R locus in several species suggests that human IGF1R CAG- mRNA
      isoform is evolutionarily more recent compared to the IGF1R CAG+ mRNA isoform and
      it could be used by the splicing apparatus at this intron/exon junction with a
      lower efficiency. This study highlights the relevance of IGF1R mRNA expression in
      neuroendocrine tumor cells, and the constant presence of 'subtle' alternative
      splicing for the IGF1R locus.

PMID- 16596195
TI  - Gene mutation analysis of sinonasal lymphomas in Indonesia.
AB  - Sinonasal lymphomas comprise NK/T-cell (NKTCL) type and B-cell type with unique
      geographical development. In this study, mutations of p53, K-ras, c-kit, beta
      catenin, and bak gene were analyzed using polymerase chain reaction (PCR)-single
      strand conformation polymorphism (SSCP) followed by direct sequencing in 41
      sinonasal lymphomas (27 NKTCL and 14 B-cell type) from Indonesia. In situ
      hybridization study with EBER-1 probe revealed that 85% of NKTCL cases were EBV
      positive, but none of B-cell type was EBV positive. Frequency of mutations in
      p53, K-ras, c-kit, beta-catenin, and bak gene was 62.9%, 0%, 11.1%, 18.5%, and
      25.9%, respectively, in NKTCL, and 71.4%, 0%, 23.1%, 21.4%, and 57.1%,
      respectively, in B-cell cases, showing that mutation frequency in all genes was
      higher in B-cell than in NKTCL cases. These findings suggest that gene mutations
      might be the driving-force for B-cell lymphoma, whereas combined EBV infection
      and gene mutations contribute to NKTCL development in Indonesia.

PMID- 16596196
TI  - Gene expression profiles with cDNA microarray reveal RhoGDI as a predictive
      marker for paclitaxel resistance in ovarian cancers.
AB  - In the current study, we identified paclitaxel-resistant related genes by
      comparing gene expression profiles of paclitaxel-resistant and parent ovarian
      cancer cell lines. Gene expression profiles of the human ovarian cancer cell line
      (KF28), cisplatin-resistant cell line (KFr13) induced from KF28, and paclitaxel
      resistant cell lines (KF28TX and KFr13TX) induced by exposing KF28 and KFr13 to
      dose-escalating paclitaxel were compared and analyzed using cDNA microarray. Of
      557 human cancer-related cDNA transcripts compared, 5 genes were found to be
      underexpressed and 5 genes overexpressed in the paclitaxel-resistant KF28TX,
      while another paclitaxel-resistant KFr13TX had 5 underexpressed and 8
      overexpressed genes. Among these genes, overexpression of the ATP-binding
      cassette subfamily (MDR-1), Rho guanine dinucleotide phosphate dissociation
      inhibitor beta (RhoGDI) and insulin-like growth factor binding protein 3 (IGFBP
      3) was observed in both paclitaxel-resistant cell lines. Using real-time
      quantitative PCR, we confirmed the array results. We therefore conclude that
      IGFBP-3, RhoGDI and MDR-1 were correlated with paclitaxel resistance. Moreover,
      immunohistochemical staining was analyzed in 22 serous ovarian cancer tissues
      from patients who received paclitaxel-based chemotherapy, and RhoGDI
      overexpression was observed more frequently in non-responsers than in responders
      (p=0.004). RhoGDI expression proved to be a predictive marker of paclitaxel
      resistance not only in paclitaxel-resistant cell lines, but also in clinical
      samples.

PMID- 16596197
TI  - Anticancer effects of low-dose 10-hydroxycamptothecin in human colon cancer.
AB  - 10-Hydroxycamptothecin (10-HCPT), an indole alkaloid isolated from a Chinese
      tree, Camptotheca acuminate, inhibits the activity of topoisomerase I and has a
      broad spectrum of anticancer activity in vitro and in vivo. However, its use has
      been limited due to its water-insolubility and toxicity with i.v. administration.
      The purpose of this study was to investigate the efficacy, toxicity and proper
      dosage of 10-HCPT as a single agent by oral administration in the treatment of
      human colon cancer. 10-HCPT significantly repressed the proliferation of Colo 205
      cells at a relatively low concentration (5-20 nM). Flow cytometry analysis and
      western blot and apoptosis assays demonstrated that low-dose 10-HCPT arrested
      Colo 205 cells in the G2 phase of the cell cycle and triggered apoptosis through
      a caspase-3-dependent pathway. Moreover, following oral administration at doses
      of 2.5-7.5 mg/kg/2 days, significant suppression of tumor growth by 10-HCPT was
      observed in mouse xenografts. No acute toxicity was observed after an oral
      challenge of 10-HCPT in BALB/c-nude mice every 2 days. The results of this study
      suggest that a relatively low dose of 10-HCPT (p.o.) is able to inhibit the
      growth of colon cancer, facilitating the development of a new protocol of human
      trials with this anticancer drug.

PMID- 16596198
TI  - Aberrant methylation of RASGRF2 and RASSF1A in human non-small cell lung cancer.
AB  - Aberrant methylation of promoter CpG that causes silencing of tumor suppressor
      genes (TSGs) may play a key role in the carcinogenesis of many cancer types.
      RASSF1A, regarded as a TSG, has been extensively studied in lung cancer and other
      malignant tumors, whereas RASGRF2 has only been reported to possibly play a role
      in the pathogenesis of pancreatic cancer cell lines. The aims of our study were
      to i) determine the methylation profile of RASGRF2 and ii) compare the
      methylation profiles of RASGRF2 with RASSF1A in lung cancer. We examined RASGRF2
      expression by reverse transcription PCR and aberrant methylation of RASGRF2 by
      methylation-specific PCR in lung cancer cell lines. Loss of RASGRF2 expression
      was presented in 36% lung cancer cell lines while aberrant methylation of RASGRF2
      was present in 30% (3/10) non-small cell lung cancer (NSCLC) cell lines and in
      25% (1/4) small cell lung cancer (SCLC) cell lines. The concordance between loss
      of expression and aberrant methylation of RASGRF2 was 86% (12/14). RASGRF2
      expression was restored after treatment with the demethylating agent, 5-aza-2'
      deoxycytidine in all four cell lines tested that downregulated RASGRF2
      expression. Among primary NSCLC, RASGRF2 and RASSF1A methylation was observed in
      34% (39/114) and 39% (44/114) of cases respectively, while it was observed in
      only 7% (4/57) and none of the corresponding non-malignant lung tissue. There is
      no correlation between RASGRF2 and RASSF1A methylation status. Both RASGRF2 and
      RASSF1A methylation did not associate with clinical characteristics. Frequent
      methylation and silencing of RASGRF2 in tumor cells may play an important role,
      different from that of RASSF1A, in the carcinogenesis of NSCLC.

PMID- 16596199
TI  - Selectively enhanced radiation sensitivity in prostate cancer cells associated
      with proteasome inhibition.
AB  - The purpose of this study is to evaluate the utility of MG-132, a broad spectrum
      proteasome inhibitor, to selectively enhance radiation sensitivity in prostate
      cancer without affecting normal surrounding urothelial tissue. PC3 prostate
      cancer cells and normal URO-tsa bladder epithelial cells were treated with or
      without MG-132 and exposed to 0, 2, 4, or 6 Gy radiation. Cell viability and
      clonogenic survival assays were performed, and nuclear factor kappa-B (NF-kappaB)
      activity was evaluated with electrophoretic mobility shift assay (EMSA). MG-132
      was associated with decreased cell viability (between 24% and 33%) and clonogenic
      survival (between 71% and 88%) alone and in combination with radiation in PC3
      cells. MG-132 had no effect on cell viability or clonogenic survival following
      radiation in URO-tsa cells. Constitutive and radiation-induced NF-kappaB binding
      activity was higher in PC3 cells compared with URO-tsa cells. Furthermore, MG-132
      at concentrations associated with reductions in cell viability and clongenic
      survival inhibited NF-kappaB binding activity in PC3 cells with no effect in URO
      tsa cells. These results provide strong evidence that proteasome inhibition and
      concomitant NF-kappaB inhibition can be used to selectively enhance tumor
      radiation sensitivity in prostate cancer without affecting normal surrounding
      bladder tissue.

PMID- 16596200
TI  - hRFI overexpressed in HCT116 cells modulates Bcl-2 family proteins when treated
      with 5-fluorouracil.
AB  - Exogenous overexpression of hRFI, originally isolated in our laboratory, inhibits
      not only death receptor-mediated apoptosis but also the mitochondrial apoptosis
      induced by several chemotherapeutic agents including 5-fluorouracil (5-FU).
      Recently, it has become clear that hRFI targets and degradates caspase-8 and -10
      in death receptor-mediated apoptosis by E3 ubiquitin activity in a ring finger
      domain homologous to that of X-chromosome-linked inhibitor of apoptosis protein
      (XIAP). However, the cellular mechanism of the inhibition of mitochondrial
      apoptosis by hRFI has not been fully elucidated. We prepared HCT116
      overexpressing hRFI (HCT116/hRFI) cells and comprehensively analyzed the
      expression changes of 51 apoptosis-related genes with or without 5-FU treatment
      between HCT116/hRFI and mock cells using microfluidic low-density arrays. As a
      result, we identified four genes (Bcl-2, Bcl-XL, cIAP2, and CFLAR) whose
      expression was four or more times higher in HCT116/ hRFI cells than in
      HCT116/LacZ cells, and found that Bcl-2 and the ratio of Bcl-2/Bax or Bcl-2/Bak
      were upregulated when HCT116/hRFI cells were treated with 5-FU. Furthermore, we
      also validated the up-regulation of Bcl-2 and Bcl-XL in HCT116/hRFI cells treated
      with 5-FU by Western blot analysis. Such evidence suggests that the modulation of
      Bcl-2 family proteins seen in 5-FU treatment plays an important role in the anti
      apoptotic function of HCT116/hRFI cells.

PMID- 16596201
TI  - Analysis of ribonucleotide reductase M2 mRNA levels in patient samples after GTI
      2040 antisense drug treatment.
AB  - This study describes the development of a rapid and practical real-time RT-PCR
      method to quantify ribonucleotide reductase M2 (RRM2) mRNA in tumor and
      peripheral white blood cells (WBCs) from patients treated with GTI-2040, an
      antisense drug currently in clinical trials. In order to assess target down
      regulation by GTI-2040, RRM2 mRNA expression levels were analyzed in pre- and
      post-treatment samples from a phase II clinical trial of GTI-2040 combined with
      capecitabine in patients with metastatic breast cancer. Target gene RRM2 mRNA
      levels were evaluated using quantitative RT-PCR method: real-time PCR (TaqMan)
      with fluorescein labeled probes on an ABI 7900HT instrument, with additional post
      processing of the data to adjust for differences in total RNA in-put across the
      samples. Data are presented from a patient for whom both biopsy and PBMC samples
      were available, demonstrating applicability of this reproducible, highly
      sensitive real-time RT-PCR method for the detection and quantification of mRNAs
      for RRM2 in human WBC and tissue samples. By providing quantitative measurement
      of changes in target gene expression, this method may provide an opportunity to
      determine the correlation between target response to GTI-2040 antisense and
      clinical response in patients. Furthermore this assay may assess whether WBC
      samples are an appropriate surrogate tissue for approximating target down
      regulation in the tumor.

PMID- 16596202
TI  - Analysis of interleukin (IL)-1beta IL-1 receptor antagonist, soluble IL-1
      receptor type II and IL-1 accessory protein in HCV-associated lymphoproliferative
      disorders.
AB  - Hepatitis C virus (HCV) causes hepatitis, liver cirrhosis and hepatocellular
      carcinoma, and may also induce type II mixed cryoglobulinemia syndrome (MC), a
      disease characterized by clonal B-cell lymphoproliferations that can evolve into
      non-Hodgkin's lymphoma (NHL). Interleukin-1 (IL-1) is a cytokine that plays an
      important role in initiating the cascade of events of immunoinflammatory
      responses through costimulation of T lymphocytes, B-cell proliferation, induction
      of adhesion molecules and stimulation of the production of other inflammatory
      cytokines. The role of IL-1 in immunoinflammatory responses is highlighted by the
      presence of endogenous regulators (IL-1 receptor antagonist, soluble receptors
      type 1 and II, human IL-1 accessory protein) that, when secreted into the blood
      stream may serve as endogenous regulators of IL-1 action. The aim of this study
      was to evaluate whether abnormalities in the blood levels of IL-1beta IL-1
      receptor antagonist, soluble IL-1 receptor type II and human IL-1 accessory
      protein in HCV+ patients are associated with development of MC and/or NHL.
      Relative to healthy controls, we observed: i) an increase in the circulating
      levels of IL-1beta in HCV+ patients simultaneously affected by NHL; ii) increased
      levels of IL-1 accessory protein in patients singly infected by HCV; iii)
      increase of IL-1 receptor antagonist in HCV+ patients and in those affected also
      by NHL with or without MC; iv) a homogeneous increase of sIL-1R type II in all
      the subgroup of patients. These data indicate that an attempt to increased
      circulating levels of IL-1 inhibitors occurs at different extent in the course of
      HCV infection as well as in its progression to NHL and/or MC.

PMID- 16596203
TI  - Is neuroendocrine cell differentiation detected using chromogranin A from
      patients with bone metastatic prostate cancer a prognostic factor for outcome?
AB  - We evaluated the usefulness of overexpression of neuroendrocrine (NE) cell
      differentiation determined by immunohistochemical staining for chromogranin A (Cg
      A) in diagnostic needle biopsy specimens of bone metastatic prostate cancers. A
      total of 50 patients diagnosed as having bone metastatic prostate cancer were
      studied. The period of observation was between 6.9 and 79.4 months (median 48.7
      months). Cg A was detected by immunostaining using the labeled streptavidin
      biotin method. Cg A-positivity was defined as the presence of immunostained cells
      in 10% or more of the tumor. All statistical analyses were carried out using the
      Statistical Package for Social Sciences Software, version 10.0 for Windows.
      Eleven patients (22%) were classified into the Cg A-positive group. There were no
      significant differences in clinical data between the Cg A-positive and Cg A
      negative groups. The 5-year cause-specific survival rate was 34.1% for the Cg A
      positive group and 55.2% for the Cg A-negative group (p=0.3763). The 3-year non
      recurrence rate was 9.1% for the Cg A-positive group and 35.9% for the Cg A
      negative group, and this difference was significant (p=0.0253). The 3-year cause
      specific survival rates after recurrence were 38.4% and 42.3% respectively
      (p=0.8125). We consider that NE cell differentiation of the primary tumor in
      cases of bone metastatic prostate cancer is not a prognostic factor for outcome.

PMID- 16596204
TI  - Expression of Foxp3 in non-small cell lung cancer patients is significantly
      higher in tumor tissues than in normal tissues, especially in tumors smaller than
      30 mm.
AB  - Active suppression by CD4+CD25+ T regulatory cells (T regs) plays an important
      role in the down-regulation of T cell responses to foreign and self-antigens.
      Thus far, the potential role of T regs in human tumors has been reported. T reg
      mediated suppression of antitumor immune responses may partly explain the poor
      clinical response to vaccine-based immunotherapy for human cancer. The forkhead
      transcription factor Foxp3 is a critical regulator of T regs development and
      function. Foxp3 represents a specific marker for the T regs. In this study, we
      measured the Foxp3 mRNA expression in tumors and in normal tissues from 46
      patients with non-small cell lung carcinoma (NSCLC), and tumor tissues showed a
      significantly higher expression of Foxp3 mRNA than normal tissues. The expression
      of Foxp3 mRNA and the tumor diameter were inversely proportional. These results
      suggest that T regs expressing Foxp3 selectively accumulate in tumor tissues of
      NSCLC and contribute to antitumor immune dysfunction, especially in the early
      stages.

PMID- 16596205
TI  - Urinary gelatinase activities (matrix metalloproteinases 2 and 9) in human
      bladder tumors.
AB  - The ability to degrade type IV collagen, the major component of the basement
      membrane, is unique to gelatinases A and B. These two matrix metalloproteinases
      (MMPs) are most often linked to the malignant phenotype of tumor cells, and their
      expression is elevated in several cases of human tumor aggressiveness and overall
      survival. By gelatin zymography, we verified MMP activity in the urine of
      patients with bladder cancer. Of these patients, 10 had well-, 8 had moderately
      and 7 had poorly differentiated bladder cancer. The urine of healthy volunteers
      with no evidence of disease was used for controls. Zymography showed five
      dominant gelatinolytic bands of 240, 220, 130, 92 and 72 kDa in tumor samples,
      whereas only traces of MMP were detected in the urine of healthy subjects. The
      majority of cancerous urine samples showed MMP-9 lytic activity but only a few
      contained MMP-2. Moreover, MMP-9 content is enhanced in the urine from patients
      with high-grade and advanced-stage bladder tumors. Finally, we determined the
      urinary levels of urinary bladder cancer (UBC), tissue polypeptide-specific
      antigen (TPS) and protein 22 of nuclear matrix (NMP22). The levels of TPS and NMP
      22 were higher in G3 bladder cancer than in G1 and G2 neoplasias. The urinary
      values of these two biomarkers correlated with the increase in MMP-9 lytic
      activity in high-grade and advanced-stage bladder cancer.

PMID- 16596206
TI  - Effects of extracts from two Native American plants on proliferation of human
      breast and colon cancer cell lines in vitro.
AB  - Native American medicinal plants are traditionally used to prevent and treat a
      variety of diseases, including cancer. These herbal preparations are alleged to
      have many biological activities, such as stimulation or suppression of immune
      responses and antiproliferative effects on cancer cells. In the present study, we
      investigated the effects of aqueous and ethanol extracts from two Native American
      plants, Ligusticum porteri (Osha) and Anemopsis californica (Yerba Manza), on the
      growth of human MCF-7/AZ breast and HCT8/E11 colon cancer cells. The aqueous and
      ethanol extracts from A. californica potently inhibited growth of MCF-7/AZ in a
      concentration-dependent manner, whereas the growth of HCT8/E11 was unaltered.
      Extracts from L. porteri showed no activity on either cell line. In addition, we
      observed that the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2)
      activities were markedly decreased when exposed to both extracts from A.
      californica. These results suggest that the growth inhibitory effect of A.
      californica in breast cancer cells is ERK-mediated.

PMID- 16596208
TI  - Relationships between dynamic contrast-enhanced MRI findings and pattern of
      invasion for tongue carcinoma.
AB  - The purpose of this study was to evaluate the effectiveness of dynamic contrast
      enhanced MRI (DC-MRI) for assessing the pattern of invasion of tongue carcinomas.
      We studied 20 cases of squamous cell carcinoma of the tongue that showed
      peripheral enhancement patterns on DC-MRI. The diameter of each tumor was >2.0 cm
      and no apparent artifacts were seen. The signal enhancement to noise ratio (SE/N)
      of the regions of interest, which were located in the central and peripheral
      regions of the tumor, were measured using DC-MRI, while maximum SE/N, %-wash out,
      and the ascending rate of SE/N were also calculated. The histopathological
      pattern of invasion was assessed in each case and used to classify them into
      clear (13 cases) and diffuse (7 cases) groups, after which the 4 parameters were
      compared between the 2 groups. The ascending rate of SE/N in the peripheral
      region was significantly lower in the diffuse group (p=0.047). There were no
      other significant differences between the 2 groups for any parameter in either
      tumor region. These results suggest that DC-MRI is able to show the
      histopathological pattern of invasion into surrounding structures.

PMID- 16596207
TI  - In vivo growth of transitional and renal cell carcinoma cell lines can be
      suppressed by the adenovirus-mediated expression of a soluble form of vascular
      endothelial growth factor receptor.
AB  - Antiangiogenic therapy is a promising strategy for the treatment of cancer since
      tumor development and metastases require angiogenesis. Vascular endothelial
      growth factor (VEGF) is one of the most important factors in tumor angiogenesis.
      In the present study, we investigated the antitumor effect of an adenovirus
      (AdVEGF-ExR) expressing the extracellular domain of the human VEGF receptor (flt
      1) using two different urological tumor/mouse systems. RENCA, a renal cell
      carcinoma of BALB/c origin, and MBT-2, a poorly differentiated transitional
      carcinoma of C3H/He origin, were used. Both types of tumor were in vitro infected
      with AdVEGF-ExR and inoculated subcutaneously into the abdomens of syngenenic
      mice, and tumor growth was measured twice weekly. In some experiments, BALB/c
      mice with established RENCA tumors were injected intramuscularly with AdVEGF-ExR
      as a therapeutic model. The cytotoxicity of spleen cells from the tumor-rejected
      mice was assessed by 51Cr-release assay. Although the in vitro cell growth of
      either MBT-2 or RENCA was not affected by infection with AdVEGF-ExR, the in vivo
      growth of both AdVEGF-ExR-infected tumors was significantly suppressed in the
      syngeneic mice. In addition, although 2 of 5 mice rejected the AdVEGF-ExR
      infected RENCA, tumor-specific cytotoxic T lymphocytes were not generated from
      their spleen cells, thus suggesting no cellular immune response. In a therapeutic
      model, intramuscular injections of AdVEGF-ExR at a remote site also significantly
      suppressed the growth of the subcutaneously established RENCA. These results
      indicate that the adenovirus-mediated expression of a soluble VEGF receptor can
      be an effective therapy for urological cancer treatment; however, such VEGF
      targeted gene therapy is not necessarily accompanied by subsequent antitumor T
      cell immunity.

PMID- 16596209
TI  - Increased tolerability of bimonthly 12-hour timed flat infusion 5
      fluorouracil/irinotecan regimen in advanced colorectal cancer: A dose-finding
      study.
AB  - A dose-finding study was designed to determine the maximum tolerated dose (MTD)
      of a bimonthly 12-h (10:00 p.m to 10:00 a.m), timed flat infusion (TFI) of 5
      fluorouracil (5-FU) plus irinotecan (CPT-11), without leucovorin (LV), for
      metastatic colorectal carcinoma (CRC). A total of 33 patients were treated. Seven
      dose levels included a fixed CPT-11 dose of 180 mg/m2 on days 1 and 15 (d(1,15))
      and escalating doses of 5-FU 600-1200 mg/m2 on days 1-4 and 15-18 (d(1-4,15-18)).
      Dose-limiting toxicities (DLTs) were: grade 3-4 non-hematologic, grade 4
      hematologic and any toxicity causing a more than a 2-week delay in treatment. The
      MTD was reached at the seventh dose level. DLTs were observed in 5/8 patients
      (63%): G3 diarrhea, 2 patients, associated with G3 mucositis in one instance; G4
      neutropenia, 2 patients, associated with severe asthenia in 1 patient; G3 hand
      foot syndrome, 1 patient. The recommended doses (RDs) were established at the
      sixth dose level: 5-FU, 1100 mg/m2/d(1-4,15-18); CPT-11 180 mg/m2/d(1,15) [5-FU
      and CPT-11 dose intensity (DI), 2200 and 90 mg/m2 per week (w), respectively]. At
      the recommended dose, the DLTs in 38 cycles were: mucositis, 2 cycles (5%);
      afebrile G4 neutropenia and hand-foot syndrome, 1 cycle (3%). In 24 assessable
      patients, the overall response rate was 37.5%. The present CPT-11/5-FU schedule
      is highly tolerable in an outpatient setting using the highest recommended 5-FU
      dose effective in advanced CRC.

PMID- 16596210
TI  - Changes in bone resorption and vascular endothelial growth factor after a single
      zoledronic acid infusion in cancer patients with bone metastases from solid
      tumours.
AB  - Zoledronic acid (Zometa, ZOL) is increasingly used to treat tumour-induced bone
      disease, and is also reported to have antiangiogenic properties in vivo. In this
      study, we have investigated the correlations between changes in the proangiogenic
      cytokine, vascular endothelial growth factor (VEGF), and markers of bone
      resorption in a cohort of patients with metastatic bone disease, following a
      single infusion of ZOL. Twenty-four consecutive selected cancer patients with
      scintigraphic and radiographic evidence of bone metastases were treated for the
      first time with a single infusion of 4 mg ZOL. Patients were considered
      ineligible if they had received any steroid therapy, radiotherapy, chemotherapy,
      immunotherapy or haemopoietic growth factors in the 4 weeks before or during the
      study period. Circulating levels of VEGF and beta crosslinked type I collagen C
      telopeptide (betaCTX) were measured at base-line and at 1, 2, 7 and 21 days
      following ZOL infusion. The majority of our patients (23/24) developed a
      significant reduction in circulating levels of betaCTX at just 1 day after the
      single zoledronic acid infusion, median percentage decrease 67.05% (95% CI,
      52.39%; 76.27%). This reduction persisted at all following time points in almost
      all subjects in our patient population (day 2, 95.8%; day 7, 100%; day 21,
      91.7%). The median decrease at day 2 was 85.67% (95% CI, 78.23%; 90.16%); at day
      7, 67.38% (95% CI, 67.38%; 86.98); and at day 21, 76.89% (95% CI, 35.00%;
      83.16%). Moreover, a linear regression model with variance analysis demonstrated
      a statistically significant correlation between median VEGF and betaCTX
      circulating levels at each of the time points (1, 2, 7 and 21 days after ZOL
      infusion). The present work demonstrates that a single infusion of ZOL was able
      to induce a rapid and long lasting decrease of betaCTX plasma levels in the
      majority (23/24) of the included cancer patients. Furthermore, we found that
      there is a correlation between the levels of VEGF and betaCTX following ZOL
      treatment. Future clinical trials should be designed to prospectively evaluate
      the prognostic role of reduction of betaCTX and VEGF in response to ZOL to
      predict clinical and skeletal outcome.

PMID- 16596211
TI  - Inhibition of Src activity enhances the tumor-suppressive effect of the connexin
      32 gene in Caki-1 renal cancer cells.
AB  - Connexin (Cx) genes exert negative growth effects on tumor cells with certain
      cell specificity. We have recently reported that Cx32 acts as a tumor suppressor
      gene in a metastatic renal cancer cell line (Caki-1) due to the inactivation of
      Src. In line with the previous study, here we investigated if an Src family
      inhibitor (PP1) could enhance the tumor-suppressive effect of Cx32 in Caki-1
      cells from human metastatic renal cell carcinoma. We examined the difference in
      the cytotoxic effect of PP1 on two cell clones, Cx32-transfected Caki-1 cells
      (Caki-1T) and mock-transfected Caki-1 cells (Caki-1W), in vitro as well as in
      vivo. PP1 showed more cytotoxic effect on Caki-1T than on Caki-1W at lower doses.
      This reinforcement was also observed in a xenograft model of nude mice. The in
      vitro reinforcement of the cytotoxic effect depended not only on control of cell
      cycle transition but also on the induction of apoptosis, and the occurrence of
      the event was mostly caused by potential inhibition of Src activity in Caki-1T.
      Also, under a hypoxic condition, which is a typical environment of tumor tissue,
      Cx32 suppressed hypoxia-induced Src activation, and PP1 enhanced cytotoxicity in
      Caki-1T. These results suggest that, in addition to the Cx32-dependent tumor
      suppressive effect, the concomitant inhibition of Src by PP1 is an effective
      procedure to induce a cytotoxic effect in Caki-1 cells.

PMID- 16596212
TI  - Plasma proteomic profiling: search for lung cancer diagnostic and early detection
      markers.
AB  - Environmental and occupational exposure to asbestos is among the established risk
      factors for lung cancer, the leading cause of cancer-related deaths in the United
      States. This link between exposure to asbestos and the excessive death rate from
      lung cancer was evident in a study of former workers of an asbestos pipe
      insulation manufacturing plant in Tyler, TX. We performed comparative proteomic
      profiling of plasma samples that were collected from nine patients within 12
      months before death and their age-, race- and exposure-matched disease-free
      controls on strong anion exchange chips using surface-enhanced laser desorption
      ionization time-of-flight mass spectrometry. A distance-dependent K-nearest
      neighbor (KNN) classification algorithm identified spectral features of m/z
      values 7558.9 and 15103.0 that were able to distinguish lung cancer patients from
      disease-free individuals with high sensitivity and specificity. The high
      correlation between the intensities of these two peaks (r=0.987) strongly
      suggests that they are the doubly and singly charged ions of the same protein
      product. Examination of these proteomic markers in the plasma samples of subjects
      from >5 years before death from lung cancer suggested that they are related to
      the early development of lung cancer. Validation of these biomarkers would have
      significant implications for the early detection of lung cancer and better
      management of high-risk patients.

PMID- 16596213
TI  - Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of
      meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer.
AB  - Leptomeningeal carcinomatosis represents a rare manifestation of metastatic
      breast cancer (MBC). A 39-year-old female presenting with HER2-overexpressing MBC
      and suffering from meningeal carcinomatosis was treated with the humanized
      antibody trastuzumab directed to HER2 by intrathecal administration. The patient
      was diagnosed with HER2-overexpressing stage III breast cancer in December 2003.
      In August 2004, the patient developed a singular intracerebral metastasis which
      was resected by neurosurgery followed by whole-brain radiotherapy. Since MRI and
      cerebrospinal fluid (CSF) analyses indicated meningeal carcinomatosis, the
      patient was commenced on trastuzumab (6 mg/kg q3w) and capecitabine (2.500 mg/m2
      d1-14, q3w). Prompted by clinical deterioration, 5 repeated doses of intrathecal
      methotrexate (15 mg/dose) were administered, yet without clinical improvement.
      There is initial evidence that trastuzumab does not reach an adequate
      concentration in CSF after intravenous application. Nevertheless, infiltration of
      trastuzumab into CSF is facilitated under conditions of an impaired blood-brain
      barrier, as it is known for meningeal carcinomatosis. For patients with
      leptomeningeal disease, intrathecal application of trastuzumab may provide an
      interesting therapeutical approach for patients with HER2 overexpressing
      metastatic breast cancer. Therefore, an Ommaya reservoir for intrathecal
      treatment with trastuzumab was placed surgically and intrathecal therapy was
      begun with escalating doses of trastuzumab (5-20 mg), which proved to be
      effective and well tolerated by the patient. Within 2 weeks after treatment, the
      patients' condition improved significantly and cell counts in CSF obtained from
      the Ommaya reservoir remained low for 11 months after first diagnosis of
      meningeal carcinomatosis when clinical symptoms and MRI indicated progression of
      meningeal and cerebral disease.

PMID- 16596215
TI  - Lactoferricin-induced apoptosis in estrogen-nonresponsive MDA-MB-435 breast
      cancer cells is enhanced by C6 ceramide or tamoxifen.
AB  - Bovine lactoferricin (LfcinB) is a cationic peptide that selectively induces
      caspase-dependent apoptosis in human leukemia and carcinoma cell lines. Ceramide
      is a second messenger in apoptosis signaling that has been shown to increase the
      cytotoxicity of various anti-cancer drugs. In this study, we determined whether
      manipulation of intracellular ceramide levels enhanced LfcinB-induced apoptosis
      of estrogen-nonresponsive MDA-MB-435 breast carcinoma cells. LfcinB caused DNA
      fragmentation and morphological changes consistent with apoptosis in MDA-MB-435
      breast cancer cell cultures, but did not affect the viability of untransformed
      mammary epithelial cells. MDA-MB-435 breast cancer cells also exhibited DNA
      fragmentation and morphological changes consistent with apoptosis following
      exposure to the cell-permeable ceramide analog C6. An additive increase in DNA
      fragmentation was observed when both LfcinB and C6 ceramide were added to MDA-MB
      435 breast cancer cell cultures. A greater than additive increase in DNA
      fragmentation was seen when LfcinB was used in combination with tamoxifen, which
      prevents the metabolism of endogenous ceramide to glucosylceramide by
      glucosylceramide synthase, as well as blocking estrogen receptor signaling.
      However, a selective inhibitor of glucosylceramide synthase,1-phenyl-2
      palmitoylamino-3-morpholino-1-propanol, failed to further increase DNA
      fragmentation by LfcinB, suggesting that tamoxifen enhanced LfcinB-induced
      apoptosis in breast cancer cells via a mechanism that did not involve
      glucosylceramide synthase inhibition. We conclude that combination therapy with
      LfcinB and tamoxifen warrants further investigation for possible use in the
      treatment of breast cancer.

PMID- 16596214
TI  - In situ gene expression and localization of metalloproteinases MMP1, MMP2, MMP3,
      MMP9, and their inhibitors TIMP1 and TIMP2 in human renal cell carcinoma.
AB  - Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role
      in the maintenance of extracellular matrix homeostasis. Alterations of MMP and
      TIMP expressions have been found in several malignant tumour entities. In this
      study the expression pattern of MMP1, MMP2, MMP3, MMP9, and their inhibitors
      TIMP1, and TIMP2 were investigated at mRNA and protein levels in human renal cell
      carcinoma (RCC). Formalin fixed paraffin embedded tumour samples of 10 patients
      and adjacent non-malignant controls were analysed by radioactive labelled
      riboprobe in situ hybridisation (isH) and immunohistochemistry. The slides were
      evaluated semiquantitatively. MMP1-antigen was strongly expressed in tumour
      epithelium with moderate stroma expression in one case. The gelatinases MMP2 and
      MMP9 showed moderate to strong signals in tumour epithelial cells at the mRNA and
      protein level, while the expression in tumour stroma was moderate. MMP3-mRNA and 
      antigen were expressed moderately to strong in tumour epithelium and focally in
      stroma cells. mRNA or TIMP1- and TIMP2-mRNA and -antigen were also predominantly
      expressed in tumour epithelium; only few samples showed positive expression in
      stroma cells. mRNA expression could be generally correlated to the protein
      expression in our study group, except for MMP1 (mRNA expression was only
      expressed in two cases). We found a pronounced expression for the gelatinases
      MMP2 and MMP9 and for MMP3 in RCC at the mRNA and protein level. The expression
      of TIMP1 and TIMP2 appears also to be relevant in RCC. Due to the small sample
      size further investigations need to be done to prove a statistical significant
      correlation between the MMP/TIMP expression and clinicopathological parameters.

PMID- 16596216
TI  - Comparative integromics on Ephrin family.
AB  - EFNA1, EFNA2, EFNA3, EFNA4, EFNA5, EFNB1, EFNB2 and EFNB3 are EFN family ligands
      for EPH family receptors. EFN/EPH signaling pathway networks with the WNT
      signaling pathway during embryogenesis, tissue regeneration, and carcinogenesis.
      Comparative genomics analyses on EFNB1, EFNB2 and EFNB3 were performed by using
      bioinformatics and human intelligence (humint). EFNB1 mRNA was expressed in human
      embryonic stem (ES) cells, neural tissues, diffuse type gastric cancer,
      pancreatic cancer, colon cancer, brain tumors and esophageal cancer, EFNB2 mRNA
      in human ES cells, neural tissues and colon cancer, EFNB3 mRNA in human ES cells,
      neural tissues, brain tumors, pancreatic cancer and colon cancer. Because triple
      TCF/LEF-binding sites were identified within the 5'-promoter region of human
      EFNB3 gene, comparative genomics analyses on EFNB3 orthologs were further
      performed. Chimpanzee EFNB3 gene, consisting of five exons, was identified within
      AC164921.3 genome sequence. AY421228.1 was not a correct coding sequence for
      chimpanzee EFNB3. Chimpanzee EFNB3 gene was found to encode a 340-amino-acid
      protein showing 99.4% and 96.6% total-amino-acid identity with human EFNB3 and
      mouse Efnb3, respectively. Three TCF/LEF-binding sites within human EFNB3
      promoter were conserved in chimpanzee EFNB3 promoter, and the second TCF/LEF
      binding site in rodent Efnb3 promoters. CpG hypermethylation of EFNB3 promoter
      with 63.2% GC content as well as deletion of EFNB3 gene closely linked to TP53
      tumor suppressor gene at human chromosome 17p13.1 should be investigated to
      elucidate the mechanism of infrequent EFNB3 upregulation in human colorectal
      cancer. EFNB3, identified as potential transcriptional target of WNT/beta-catenin
      signaling pathway, is a pharmacogenomics target in the fields of regenerative
      medicine and oncology.

PMID- 16596217
TI  - Significant overexpression of SPARC/osteonectin mRNA in pancreatic cancer
      compared to cancer of the papilla of Vater.
AB  - Cancer of the papilla of Vater (CPV) has a significantly better outcome compared
      to pancreatic cancer (PC) after curative resection. Increasing evidence suggests
      that prognostic differences are influenced by a different tumor biology. Secreted
      protein acidic and rich in cystein (SPARC)/osteonectin is a multifunctional
      matricellular protein involved in cell-matrix interactions and might be involved
      in tumor pathogenesis and progression. We examined quantitative SPARC mRNA
      expression in CPV and PC to evaluate if varying expression might contribute to
      the different biologic behaviour of these entities. Quantitative real-time
      reverse transcription-PCR was performed to analyze expression of SPARC mRNA in a
      series of 31 PC and 8 CPV specimens and corresponding uninvolved pancreatic
      tissues. Relative mRNA levels (ratio tumor/normal) were calculated as (SPARC/beta
      actin in tumor)/(SPARC/beta-actin in paired normal tissue). SPARC expression
      levels were associated with clinical and histopathological parameters. SPARC mRNA
      expression was detected in all tumor and normal tissues of the pancreas and
      papilla of Vater. In pancreatic cancer, 15/31 (48.4%) patients showed
      overexpression of SPARC (ratio tumor/normal >1) whereas in CPV only 1/8 (12.5%)
      exhibited SPARC overexpression and this difference was statistically significant
      (p<0.05, Mann-Whitney test). No associations were detected with T- and N
      categories, grading or prognosis. In conclusion, SPARC mRNA overexpression is
      significantly more frequent in CP than CPV and adds further evidence that CP and
      CPV are biologically different tumor entities.

PMID- 16596218
TI  - Cimetidine, an unexpected anti-tumor agent, and its potential for the treatment
      of glioblastoma (review).
AB  - Cimetidine (CIM), the prototypical histamine H2 receptor antagonist (H2RA), was
      brought to market based on its ability to accelerate healing of gastrointestinal
      ulcers through the inhibition of gastric acid secretion. Cimetidine, the most
      studied H2RA, has been demonstrated to possess anti-tumor activity against colon,
      gastric and kidney cancers, and melanomas. This activity involves a number of
      different mechanisms of action: a) CIM antagonizes tumor cell-mediated
      interleukin-1-induced activation of selectins in liver sinusoids, inhibiting
      tumor cell binding on liver sinusoids, thereby reducing the development of liver
      metastasis; b) histamine acts as a growth factor in various tumor cell types via
      the activation of H2 receptors; CIM therefore may antagonize this effect; c) CIM
      acts as an immunomodulator by enhancing the host's immune response to tumor
      cells. With respect to malignant gliomas, CIM added to temozolomide was superior
      in vivo when compared to temozolomide alone in extending survival of nude mice
      with human glioblastoma cells orthotopically xenografted into their brain. We
      review the various mechanisms of action potentially associated with the
      therapeutic effects of CIM in the case of experimental glioblastomas,
      observations we hope will encourage clinical investigation of CIM in the
      management of highly malignant gliomas.

PMID- 16596220
TI  - Esophageal squamous cell carcinomas with distinct invasive depth show different
      gene expression profiles associated with lymph node metastasis.
AB  - We examined the gene expression profiles of esophageal squamous cell carcinomas
      (ESCCs) with respect to degree of invasive depth and lymph node (LN) involvement
      in a large cohort. We used high-density oligonucleotide microarrays to examine
      the expression of 22,115 genes in 54 ESCCs and 11 non-cancerous esophageal
      tissues. We found that 4,155 genes were biologically significant in both ESCC and
      non-cancerous esophageal tissue by analysis of Present Call (hybridization
      quality by Affymetrix) throughout all samples. From these genes, we used a
      supervised learning method to select genes responsible for the development of
      ESCC. We found that 999 genes were expressed differentially in pT1/pN0 tumors vs.
      non-cancerous esophageal tissue. In the same manner, 48, 66 and 30 genes were
      expressed differentially in pT1/pN0 tumors vs. pT1/pN1 tumors, pT1/pN0 tumors vs.
      pT2-4/pN0 tumors and pT2-4/pN0 tumors vs. pT2-4/pN1 tumors, respectively.
      Intriguingly, there were no overlaps between the 48 LN metastasis-related genes
      of pT1 tumors and the 30 LN metastasis-related genes of pT2-4 tumors, suggesting
      that ESCCs with distinct invasive depths express different genes linked to LN
      metastasis. Our present results suggest that the degree of invasive depth must be
      considered when predicting LN metastasis of ESCC from gene expression profiles.

PMID- 16596219
TI  - Cytoplasmic p21WAF1/CIP1 correlates with Akt activation and poor response to
      tamoxifen in breast cancer.
AB  - P21WAF1/Cip1 (p21) translocates to the cytoplasm inducing cell cycle progression
      and survival upon Akt/PKB activation. We studied whether heregulin beta1
      (HRGbeta1), that activates the PI3K/Akt and MAPK pathways, also misallocates p21.
      We also explored whether HRGbeta1 interferes with the effects of tamoxifen. The
      clinical material studied helped us to clarify whether p21 was associated with
      phosphorylated Akt, recurrence-free survival and response to tamoxifen. MCF-7
      cells treated with HRGbeta1 -/+ E2 were analyzed by flow cytometry to observe how
      the different compounds affected tamoxifen-induced cell cycle arrest and
      apoptosis. Total cell lysate and nuclear and cytoplasmic fractions were used to
      detect p21, phospho-Akt and other proteins by Western blotting.
      Immunofluorescence was used to visualize p21+ cells upon HRGbeta1 and E2
      stimulation. The localization of p21 in breast cancer was studied by
      immunohistochemistry in frozen tumor sections from 280 patients. In MCF-7 we
      found that HRGbeta1 counteracted the inhibition of p21 expression by tamoxifen
      and caused p21 cytoplasmic accumulation. HRGbeta1 partially counteracted the
      cytostatic effect of tamoxifen but abrogated its cytotoxic effect. The clinical
      material revealed that nuclear p21 (P=0.022) and cytoplasmic p21 (P=0.00001) were
      associated with phospho-Akt. Based on p21 cell location, we identified 3
      subgroups of ER+ patients: the p21N+/C- group for whom tamoxifen was needed
      otherwise the survival was poor (P=0.0082), the p21N+/C+ or p21N-/C- group, that
      responded to tamoxifen (P=0.034), and the p21C+/N- group, that might not benefit
      from this treatment (P=0.7). In conclusion, HRGbeta1 inhibits tamoxifen-induced
      apoptosis, contributes to p21 cytoplasmic expression while the cellular
      localization of p21 interacts with the benefit from tamoxifen treatment.

PMID- 16596221
TI  - Caspase-2: a possible trigger of apoptosis induced in A-549 tumor cells by ZnPc
      photodynamic treatment.
AB  - Photodynamic therapy applied to cell cultures represents a widely accepted
      experimental method to investigate molecular mechanisms that lead to apoptotic
      cell death. In this context the subcellular localization of photosensitizers
      seems to be a significant factor in order to determine the apoptotic pathway that
      could be activated. We have characterized the experimental conditions that induce
      apoptotic cell death in A-549 cells incubated with ZnPc and irrradiated with red
      light. Previously we have found that in this cell line the drug is localized in
      the Golgi apparatus after 3-h incubation. Indirect immunofluorescence analysis of
      the events that lead to apoptosis made possible the detection of caspase-2
      activation in the Golgi region immediately after photodynamic treatments. A few
      minutes later, the morphology of this organelle starts to disrupt and just 6 h
      after treatment the nuclei appear affected showing the fragmented appearance
      typical of apoptotic cell death. From this results we assume that following the
      photodynamic treatment of A-549 cells with ZnPc, the activation of caspase-2 in
      the Golgi apparatus could begin to initiate immediately the apoptotic process.

PMID- 16596222
TI  - cDNA microarray analysis of non-selected cases of acute myeloid leukemia
      demonstrates distinct clustering independent of cytogenetic aberrations and
      consistent with morphological signs of differentiation.
AB  - Acute myeloid leukemia (AML) is a heterogeneous disease with respect to biology
      and clinical course. Until now the basis for prognostic evaluation and
      therapeutic decision has been the karyotype, genetic FLT3 abnormalities and the
      initial chemotherapy response. A question that has emerged is if extensive gene
      expression analysis may supplement or partly replace current diagnostics. In an
      attempt to address this question, we performed cDNA microarray analysis on
      peripheral blood samples of 25 patients with newly diagnosed AML with high blast
      counts. The patients were randomly selected from a large group of consecutive
      patients. Leave-one-out crossvalidation (LOOCV) showed with high accuracy that
      gene expression classifiers could predict if leukaemia samples belonged to the
      FAB AML-M1 or to the FAB AML-M2 groups. An unsupervised two-dimensional
      hierarchical cluster analysis generated 3 patient subgroups. Except for an
      accumulation of samples classified as FAB M1 and M2 in cluster 3, there was no
      evident relationship between the clusters and the FAB classification. Each
      subgroup displayed clearly distinguished gene expression patterns validated using
      real-time quantitative PCR analysis. The identification of specific gene
      expressions that together constitute regulatory modules must complement cluster
      analyses in order to achieve an accurate basis for prognosis and prediction.

PMID- 16596224
TI  - Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens and T cell
      infiltration in non-small cell lung carcinoma and their prognostic significance.
AB  - Cancer-testis (CT) antigens were identified as a group of highly attractive
      targets for cancer immunotherapy because of their expression in a variety of
      malignant tumors but solely in the testis among the normal adult tissues. To
      evaluate the potential of two members of this family, MAGE-A4 and NY-ESO-1
      antigens, for cancer vaccine in non-small cell lung carcinoma (NSCLC), we
      examined the expression of these antigens and T cell infiltration in tumor
      tissue, and evaluated their prognostic significance. One hundred fifty-seven
      patients with NSCLC were studied. Reverse transcription-PCR was performed to
      evaluate MAGE-A4 and NY-ESO-1 expression. Immunohistochemistry was performed for
      NY-ESO-1 expression and T cell infiltration into the tumor site. Survival
      analysis was also performed. MAGE-A4 and NY-ESO-1 were expressed in 40 of 141
      (28.4%) and 13 of 157 (8.3%) NSCLC respectively. Both CT antigens were more
      frequently expressed in squamous cell carcinoma (SCC) than in adenocarcinoma. An
      inverse correlation was found between MAGE-A4 expression and patient survival in
      advanced stage cancers. Combined infiltration of both CD4+ and CD8+ T cells into
      tumor nest predicted better survival. There was no correlation, however, between
      lymphocyte infiltration and antigen expression in the tumor. MAGE-A4 expression
      in advanced group and T cell infiltration may provide prognostic information.
      Lastly, these CT antigens, especially MAGE-A4, may represent potential targets
      for cancer immunotherapy in patients with NSCLC.

PMID- 16596223
TI  - Abnormal activation of the synuclein-gamma gene in hepatocellular carcinomas by
      epigenetic alteration.
AB  - Liver cancer is the fifth most common neoplastic disease and the fourth leading
      cause of cancer-related death. Identification of the key molecular targets
      involved in hepatocarcinogenesis has significant therapeutic implications. In
      this study, by conducting immunohistochemistry, we show that the neuronal
      protein, synuclein-gamma (SNCG), is abnormally expressed in a high percentage of
      liver cancer (46/70, 65.7%). The expression of SNCG in liver cancer exhibits a
      clear stage-specific pattern of low expression in stage I (1/19, 5.3%) and high
      expression in stages III to IV (44/50, 88%). Importantly, all patients with
      metastatic diseases expressed SNCG in their primary tumors (15/15, 100%).
      Consistent with the IHC results, RT-PCR assays demonstrate that SNCG mRNA is
      highly expressed in the tumor tissue of advanced hepatocellular carcinomas.
      Analyses of the methylation status of the CpG island of the SNCG gene by
      methylation-specific PCR confirmed that all tumor samples contained the
      demethylated gene. To determine whether demethylation of SNCG is an early event
      of genetic abnormality in the process of hepatocarcinogenesis, we examined the
      methylation status of SNCG in 70 non-malignant cirrhotic liver samples and showed
      that 64.3% cirrhotic liver samples contained the partially or completely
      demethylated gene. We further show that SNCG expression in liver cancer is not
      restricted to HBV- and HCV-infected tumors, implying the involvement of other
      hepatocarcinogenic risk factors in SNCG gene reactivation. Utilizing human
      hepatoma-derived cell line HepG2 as an in vitro model, we demonstrate that
      hepatic carcinogens aflatoxin B1 and N-nitrosodimethylamine (DMN) are strong
      inducers of SNCG expression. Collectively, these new findings suggest that SNCG
      protein expression in primary tumors is a strong indicator of distant metastasis
      and demethylation of SNCG CpG island is an early sign of genetic abnormality in
      liver cirrhosis preceding hepatocarcinogenesis. Our studies also suggest that
      inducing demethylation of SNCG by hepatocarcinogens may represent one underlying
      mechanism for the aberrant expression of SNCG in HCC.

PMID- 16596225
TI  - Quantitative real-time RT-PCR monitoring of BCR-ABL in chronic myelogenous
      leukemia shows lack of agreement in blood and bone marrow samples.
AB  - Molecular monitoring of the BCR-ABL transcript in chronic myelogenous leukemia
      (CML) using quantitative RT-PCR provides clinicians with important diagnostic and
      prognostic information. To determine whether molecular detection and monitoring
      of CML is comparable using peripheral blood (PB) and bone marrow (BM) aspirate
      samples, we performed a prospective study using quantitative real-time RT-PCR
      (QRT-PCR) of paired PB and BM samples from 41 patients with CML entered onto a
      single Cancer and Leukemia Group B (CALGB) treatment study. QRT-PCR analysis of
      PB and BM samples was performed prior to initiation of, and during, treatment
      with homoharringtonine and cytarabine on a CALGB study for previously untreated
      CML. Statistical analyses demonstrated good agreement of PB and BM pre-treatment
      samples. However, using the Bland-Altman statistical method that measures true
      agreement between PB and BM values, we found that there was only modest agreement
      of BCR-ABL measurements in PB and BM for samples obtained during treatment. PB
      values obtained during treatment tended to be lower than the corresponding BM
      values [average difference = -0.37 (p<0.001) in 36 paired samples] and the 95%
      limits of agreement ranged from -1.23 to 0.48. Nevertheless, our study
      demonstrates that BM and PB QRT-PCR values followed a similar trend during
      treatment (Spearman correlation coefficient, 0.83; 95% CI, 0.70, 0.96). Our data
      suggest that, quantitatively, PB and BM measurements of BCR-ABL are frequently
      disparate. Since BM values tended to be higher than PB values, BM sampling
      provides the most accurate assessment of minimal residual disease (MRD). Based on
      these results, we caution against interchanging BM with PB sampling for MRD
      monitoring during treatment of CML since this may lead to misinterpretation of
      treatment results.

PMID- 16596226
TI  - A modified random oligonucleotide-based combination therapy for adjuvant
      treatment of pancreatic ductal adenocarcinoma.
AB  - Anti-cancer therapy in pancreatic ductal adenocarcinoma (PDAC) is mostly based on
      surgical removal or palliative therapy using antimetabolites, like 5'
      fluorouracil or gemcitabine. Adjuvant treatment using these chemotherapeutics has
      recently proven a beneficial concept, though general survival rates are still
      poor. Most recently, combination therapy of gemcitabine with other targeted drugs
      was evaluated in clinical trials. We present here a study performed in a mouse
      orthotopic xenotransplant model of PDAC, using an oligo-nucleotide-based
      approach. We have shown previously that antisense oligonucleotides against p53
      reduce the weight of orthotopic pancreatic tumours in immune-deficient mice. We
      further characterised terminal modifications of phosphorothioate oligonucleotides
      in vitro and found a random, unrelated control sequence carrying a D,L-alpha
      tocopherol modification at the 5' and 3' ends to be most efficient in induction
      of cell death in PancTu-1 cells. Modified random oligonucleotide (MRON) were thus
      further tested in vivo. MRON showed a reduction of tumour weight in established
      primary orthotopic tumours in SCID/bg mice. In a surgically adapted pre-clinical
      model, where primary tumours were resected and animals received adjuvant
      treatment, MRON was very efficient in suppression of relapse and metastasis, when
      combined with gemcitabine. While the exact molecular mechanism of MRON activity
      still needs to be elucidated, the compound showed a remarkable preference for
      uptake into tumour cells in vivo.

PMID- 16596227
TI  - Pilot study examining tumor expression of RAD51 and clinical outcomes in human
      head cancers.
AB  - Radiation therapy and chemotherapy are commonly used treatments for head and neck
      cancer. RAD51 is a highly conserved DNA repair protein that serves a central
      function in the homologous recombination pathway. High levels of RAD51 protein
      expression have been reported in number of human cancer cell lines, and studies
      suggest that RAD51 overexpression can increase cellular resistance to radiation
      and some chemotherapeutic drugs. In this study, RAD51 protein levels were
      quantified by immunohistochemistry in tumor samples from twelve head and neck
      cancer patients who received identical treatment with induction chemotherapy
      (paclitaxel and carboplatinum) followed by radiation therapy given concurrently
      with additional chemotherapy (paclitaxel, fluorouracil, hydroxyurea). Patients
      with high RAD51 protein levels in their pre-treatment tumor biopsies demonstrated
      poorer cancer-specific survival rates than patients with lower RAD51 levels
      (33.3% vs. 88.9% at 2 years; p=0.025). In addition, within a subgroup of patients
      with normal tumor cell p53 expression, there was a non-significant trend toward
      better induction chemotherapy response rates observed in the tumors with lower
      RAD51 protein levels. These results suggest that tumor cell RAD51 expression
      levels may influence the outcome of patients with head and neck cancer treated
      with chemotherapy and radiotherapy.

PMID- 16596228
TI  - Noscapine inhibits hypoxia-mediated HIF-1alpha expression andangiogenesis in
      vitro: a novel function for an old drug.
AB  - Overexpression of hypoxia-inducible factor-1 (HIF-1) is a common feature in solid
      malignancies related to oxygen deficiency. Since increased HIF-1 expression
      correlates with advanced disease stage, increased angiogenesis and poor
      prognosis, HIF-1 and its signaling pathway have become targets for cancer
      chemotherapy. In this study, we identified noscapine to be a novel small molecule
      inhibitor of the HIF-1 pathway based on its structure-function relation-ships
      with HIF-1 pathway inhibitors belonging to the benzylisoquinoline class of plant
      metabolites and/or to microtubule binding agents. We demonstrate that noscapine
      treatment of human glioma U87MG and T98G cell lines exposed to the hypoxic
      mimetic agent, CoCl2, inhibits hypoxia-mediated HIF-1alpha expression and
      transcriptional activity as measured by decreased secretion of VEGF, a HIF-1
      target gene. Inhibition of hypoxia-mediated HIF-1alpha expression was due, in
      part, to its ability to inhibit accumulation of HIF-1alpha in the nucleus and
      target it for degradation via the proteasome. One mechanism of action of
      microtubule binding agents is their antiangiogenic activity associated with
      disruption of endothelial tubule formation. We show that noscapine has similar
      properties in vitro. Thus, noscapine may possess novel antiangiogenic activity
      associated with two broad mechanisms of action: first, by decreasing HIF-1alpha
      expression in hypoxic tumor cells, upregulation of target genes, such as VEGF,
      would be decreased concomitant with its associated angiogenic activity; second,
      by inhibiting endothelial cells from forming blood vessels in response to VEGF
      stimulation, it may limit the process of neo-vascularization, correlating with
      antitumor activity in vivo. For more than 75 years, noscapine has traditionally
      been used as an oral cough suppressant with no known toxic side effects in man.
      Thus, the studies reported here have found a novel function for an old drug.
      Given its low toxicity profile, its demonstrated antitumor activity in several
      animal models of cancer and its potential to inhibit the HIF-1 pathway, noscapine
      should be considered as an antiangiogenic chemotherapy for glioma.

PMID- 16596229
TI  - The aspirin metabolite, salicylate, inhibits 7,12-dimethylbenz[a]anthracene-DNA
      adduct formation in breast cancer cells.
AB  - There is evidence that aspirin and other non-steroidal anti-inflammatory drugs
      may be protective agents against cancer in the gastrointestinal tract. These
      effects are particularly well documented for the colon and rectum. Some
      epidemiological and experimental studies have suggested that aspirin could also
      be a chemopreventive agent against breast cancer. We investigated the effects of
      the aspirin metabolite, salicylate (SA), on 7,12-dimethylbenz[a]anthracene (DMBA)
      DNA adduct formation as well as on the expression of the enzymes involved in the
      carcinogen bioactivation pathway, in particular cytochrome P450 1A (CYP1A) and
      cyclooxygenases (COX-1 and COX-2). The effects of the test drug were examined in
      both the human mammary carcinoma cell line, MCF-7, and mammary cells derived from
      DMBA-induced rat mammary tumours (RMTCs). In this study, we also reported the
      effects of SA on cell growth and viability in breast cancer cells (BCCs). The
      results demonstrated that DMBA-DNA adduct formation in both cancer cell lines was
      inhibited by SA at concentrations of > or = 2.5 mM. CYP1A was undetectable in
      RMTCs while CYP1A induction by beta-naphthoflavone in MCF-7 cells was
      significantly inhibited by SA in a concentration-dependent manner. Aspirin did
      not affect COX-1 expression in either of the BCCs. COX-2 was not detected in MCF
      7 cells, but its expression in RMTCs was inhibited by SA treatment, which also
      significantly reduced BCC growth, but failed to cause cell death by necrosis or
      apoptosis. These data suggest that inhibition of DMBA-DNA adduct formation may
      contribute to aspirin breast cancer chemopreventive action and indicate that this
      drug can act in the first stage of carcinogenesis.

PMID- 16596230
TI  - Intensity-modulated radiation therapy in advanced head and neck patients treated
      with intensive chemoradiotherapy: preliminary experience and future directions.
AB  - We review our recent experience with intensity-modulated radiation therapy (IMRT)
      and conventional three-dimensional radiation therapy (C3DRT) in advanced head and
      neck cancer. Sixty-nine patients with Stage IV head and neck cancer (and stage
      III base of tongue and hypopharynx) enrolled in a Phase II study of definitive
      chemoradiation; 20 received all or part of their radiation with IMRT. Image
      guided set-up, using video subtraction techniques, was used in all patients. Six
      weekly doses of induction carboplatin (AUC=2) and paclitaxel (135 mg/m2) were
      followed by alternating weekly chemoradiation to 75 Gy with 1.5 Gy BID fractions,
      concurrent with paclitaxel (100 mg/m2/week), 5-fluorouracil (600 mg/m2/d) and
      hydroxyurea (500 mg PO BID). Two consecutive cohorts enrolled, differing in
      radiation scheme: 75 Gy to gross disease in both, 60 or 54 Gy to first echelon
      lymphatics and 45 or 39 Gy to second echelon lymphatics. With a median follow-up
      of 47 months, 3-year overall survival is 68.5% and 3-year locoregional control is
      94.0%, with no significant differences between those treated with C3DRT versus
      IMRT, nor between the two radiation dosing schemes. Actuarial overall survival
      without tracheostomy or laryngectomy, or without a gastrostomy tube was also
      similar. Acute mucositis, dermatitis and pain were similar with C3DRT and IMRT.
      Preliminary data suggests IMRT is well tolerated, and does not compromise
      locoregional control, indicating that IMRT adequately covers the clinical volume
      at risk. Building on the present clinical experience, future directions include
      more directed efforts at reducing toxicity, with better planning software and
      planning techniques.

PMID- 16596231
TI  - Chemosensitivity prediction in esophageal squamous cell carcinoma: novel marker
      genes and efficacy-prediction formulae using their expression data.
AB  - Esophageal cancer is a highly lethal disease and the optimal therapy remains
      unclear. Since adjuvant chemotherapy gives a better chance of survival, we
      attempted to develop a chemosensitivity prediction model to improve individual
      responses to therapy. Comprehensive gene expression analyses (cDNA and
      oligonucleotide microarrays) and MTT assay of 8 drugs in 20 KYSE squamous cell
      carcinoma cell lines were performed to distinguish candidate marker genes whose
      expression levels reproducibly correlated with cellular drug sensitivities. After
      confirmation with real-time RT-PCR, we performed multiple regression analyses to
      develop drug-sensitivity prediction formulae using the quantified expression data
      of selected marker genes. Using the same sets of genes, we also constructed
      prediction models for individual clinical responses to 5-FU-based chemotherapy
      using 18 cases. We selected 5 better marker genes, known as drug sensitivity
      determinants, identified 9 novel predictive genes for 4 of 8 anticancer drugs [5
      FU, CDDP, DOX, and CPT-11 (SN-38)], and developed highly predictive formulae of
      in vitro sensitivities to the 4 drugs and clinical responses to 5-FU-based
      adjuvant chemotherapies in terms of overall and disease-free survivals. Our
      selected genes are likely to be effective drug-sensitivity markers and formulae
      using the 9 novel genes would provide advantages in prediction.

PMID- 16596232
TI  - Generation of tumor-reactive effector lymphocytes using tumor RNA-introduced
      dendritic cells in gastric cancer patients.
AB  - Anti-tumor effector cells were generated by stimulating peripheral blood
      lymphocytes with cultured dendritic cells (DCs) and mRNA extracted from the
      gastric cancer cell line MKN45 or ascites tumor cells of gastric cancer patients.
      DCs were generated from an adherent fraction of peripheral blood mononuclear
      cells (PBMCs) in the presence of GM-CSF and IL-4. mRNA was extracted from tumor
      cells and subjected to T7-amplification. The DCs were electroporated (150 V/150
      microF) with amplified mRNA and used after maturation with TNF-alpha to stimulate
      PBMCs to generate tumor RNA-introduced DC-activated killer (TRiDAK) cells. It was
      found that tumor RNA could efficiently be introduced into cultured DCs by
      electroporation (55% efficiency, 78% viability), and tumor RNA-introduced DCs
      could reproducibly stimulate lymphocytes to be tumor-reactive TRiDAK cells. The
      TRiDAK cells expressed an IFN-gamma response specific for tumor cells, but not
      for normal cells. Mock DCs or normal cell RNA-introduced DCs did not induce any
      killer cells. RNA-specific recognition of the effector cells generated was
      demonstrated using an amplified EGFP-mRNA system. The tumor killing activity of
      TRiDAK cells was inhibited not only with the anti-HLA class I antibody but also
      with the anti-HLA class II antibody as well as the anti-TCR antibody. TRiDAK
      cells reactive with autologous tumor cells could be generated in a CEA-positive
      gastric cancer patient with malignant ascites, in whom effector cell generation
      using DCs and CEA peptides had failed. These results suggest that TRiDAK cell
      generation is safe, feasible, and active in gastric cancer patients with
      malignant ascites, and is superior to other effector cell generation systems
      using DCs and epitope peptides. The adoptive immunotherapy of cancer using TRiDAK
      cells may be warranted in a clinical setting. This is the first study
      investigating anti-tumor effector cell generation using cultured DCs and tumor
      mRNA from gastric cancer cells.

PMID- 16596233
TI  - Characterization of the glycosylation profile of the human breast cancer cell
      line, MDA-231, and a bone colonizing variant.
AB  - The mechanisms that guide organ-specific metastases are not fully established.
      The aberrant expression of carbohydrates may play a fundamental role in defining
      the molecular mechanisms for metastases to distant organs and facilitate positive
      interactions within the target organ. The purpose of the present study was to
      determine the glycomic profile of a variant of the MDA-MB-231 breast cancer cell
      line that colonizes the bone and to ascribe mechanistic functions mediated by
      carbohydrates that might correlate with clinical bone metastases. The
      carbohydrate expression profiles of osteolytic MDA-MET breast cancer cells and
      non-osteolytic parental MDA-MB-231 cells were determined. MDA-MET cells were
      derived from MDA-MB-231 cells by in vivo selection of metastatic bone lesions
      following intracardiac inoculation. The two related breast cancer cell lines
      expressed distinct carbohydrate profiles; MDA-MET cells displayed an increased
      expression of alpha (2,6) linked sialic acid, N-beta1-6 GlcNAc, and sialylated
      Lewis-A antigen, and decreased expression of Galbeta1,3GalNAc as detected using a
      combination of lectins and anti-carbohydrate antibodies. Microarray analysis
      demonstrated an increased expression of glycosyltransferase genes, correlative
      for the distinct glycomic phenotype. The altered glycomic phenotypes of MDA-MET
      cells include effects on the differential binding to bone marrow endothelial
      cells, enhanced ECM binding and an increase in invasive potential. These data
      suggest that the glycomic phenotype of MDA-MET cells is associated with a select
      set of accumulated functions that collectively impact on the bone metastases and
      bone colonization capacity of breast cancer cells.

PMID- 16596234
TI  - Modulation of estrogen receptor-beta isoforms by phytoestrogens in breast cancer
      cells.
AB  - High consumption of phytoestrogen-rich food correlates with reduced incidence of
      breast cancer. However, the effect of phytoestrogens on growth of pre-existing
      breast tumors presents concerns when planning the use of phytoestrogens as
      chemoprevention st rategy. Genistein, the active phytoestrogen in soy, displays
      weak estrogenic activity mediated by estrogen receptor (ER) with a preferential
      binding for the ER-beta species. However, no information is at present available
      on the interaction between phytoestrogens and the various isoforms generated by
      alternative splicing. In two human breast cancer cell lines, T47D and BT20, which
      express variable levels of ER-beta, the effect of genistein and quercetin was
      evaluated singly and in comparison with 17beta-estradiol, on mRNA expression of
      estrogen receptor-beta (ER-beta) isoforms evaluated by a triple primer RT-PCR
      assay. In T47D cells estradiol caused a 6-fold up-regulation of total ER-beta,
      and modified the relative expression pattern of the various isoforms, up
      regulating the beta2 and down-regulating the beta5 isoform. Genistein up
      regulated ER-beta2 and ER-beta1 in T47D cells, and after treatment the ER-beta2
      isoform became prevalent, while in BT20 cells it almost doubled the percent
      contribution of ER-beta1 and ER-beta2 to total ER-beta. Quercetin did not alter
      the total levels nor the percent distribution of ER-beta isoforms in either cell
      line. Genistein, through the modulation of ER-beta isoform RNA expression
      inhibited estrogen-promoted cell growth, without interfering on estrogen
      regulated transcription. ER-beta and its ER-beta mRNA isoforms may be involved in
      a self-limiting mechanism of estrogenic stimulation promoted either by the
      natural hormone or by weaker estrogen agonists like genistein.

PMID- 16596235
TI  - Acyclic retinoid, a novel synthetic retinoid, induces growth inhibition,
      apoptosis, and changes in mRNA expression of cell cycle- and differentiation
      related molecules in human colon carcinoma cells.
AB  - Acyclic retinoid (ACR), a novel synthetic retinoid, has been demonstrated by us
      to inhibit the in vitro growth of human hepatoma cells, and this effect was
      associated with modification of cell cycle control molecules, suggesting that
      this agent may be useful in the chemoprevention and therapy of various types of
      malignancies. However, whether or not ACR exerts anticancer activities on human
      colon carcinoma cells has not yet been elucidated. The purpose of this study was
      to examine the inhibitory effects of ACR in human colon carcinoma cells and to
      characterize the molecular mechanism of action of this agent. ACR inhibited the
      growth of the HCT116 and SW480 human colon carcinoma cell lines with IC50 values
      of about 30 and 60 microM, respectively. ACR also induced G1-phase cell cycle
      arrest and apoptosis in these cell lines. When the HCT116 cells were treated with
      5-25 microM ACR, there was a marked decrease in the cellular levels of cyclin D1
      mRNA and an approximate 2.5- to 3-fold increase in those of p21CIP1 mRNA, and
      this induction occurred via a p53-independent mechanism. Furthermore, ACR induced
      a dose-dependent mRNA elevation of differentiation markers at concentrations of
      ACR that affect the levels of expression of p21CIP1. These novel results suggest
      that ACR inhibits cell proliferation by inducing G1 arrest and apoptosis and that
      cyclin D1 and p21CIP1 play critical roles in the molecular mechanisms of growth
      inhibition and differentiation induced by ACR. Collectively, these findings
      provide further evidence that ACR may be a potential agent for the
      chemoprevention and therapy of human colon cancer.

PMID- 16596236
TI  - Interleukin-2 augmented activation of tumor associated macrophage plays the main
      role in MHC class I in vivo induction in tumor cells that are MHC negative in
      vitro.
AB  - The contribution of tumor associated macrophage (TAM) to the induction of major
      histocompatibility complex (MHC) class I expression in vivo has not been reported
      precisely. In this study, we utilized Interleukin-2 (IL-2) cDNA-introduced B16
      melanoma cells (B16/IL-2) and vehicle-alone control cells (B16/mock) to examine
      whether TAM could contribute to the induction of MHC class I on B16 cells in
      vivo. Interestingly, although B16/mock and B16/IL-2 did not express MHC class I
      in vitro, MHC class I was strongly expressed in vivo in B16/IL-2 in comparison to
      B16/mock. Although in vivo treatment of anti-NK1.1 antibody abolished MHC
      expression in B16/mock in vivo, the same treatment did not influence MHC
      expression in B16/IL-2. Interestingly, both anti-asialo GM1 and anti-CD11b
      treatment strongly decreased MHC expression in B16/IL-2. TAM expressed both
      asialo GM1 and CD11b antigen, and TAM recovered from B16/IL-2 produced interferon
      gamma (IFNgamma) 6 times more than that from B16/mock. In addition, TAM recovered
      from B16/IL-2 secreted 33.64 times more IFNgamma in response to in vitro
      administration of IL-2. Therefore, we checked whether or not IL-2 could influence
      the expression of IL-2 receptors. TAM recovered from IL-2 expressed middle
      affinity receptor of IL-2 (CD122 and CD132) while that from B16/mock expressed
      low affinity receptor (CD25 and CD132). Finally, we observed that B16 cells
      became apoptotic with IFNgamma treatment in vitro. These results suggested that
      IL-2 augmented activation of TAM would play the main role in induction of the MHC
      class I molecule through secretion of IFNgamma, and would contribute to the
      IFNgamma-mediated apoptosis induction in tumor cells.

PMID- 16596237
TI  - HAUSP as a therapeutic target for hematopoietic tumors (review).
AB  - p53, one of the most important tumor suppressor proteins, plays an essential role
      in regulating the cell cycle and apoptosis by sensing the integrity of genome.
      Therefore, the level of p53 protein is critical for normal cellular homeostasis,
      and is known to be subtly regulated by ubiquitination and deubiquitination
      systems. Numerous genetic alterations of p53 have been reported in all types of
      tumors. In hematopoietic tumors, the mutations of p53 gene are rare compared with
      solid tumors, which showed more than 50% frequency for p53 mutations. According
      to this characteristic feature of hematological tumors, the therapeutic strategy
      for targeting the level of p53 may be valuable in anti-cancer treatment of
      hematological tumors. Herein, we deal with the post-translational regulation of
      p53 via its specific ubiquitinating enzymes (Mdm2, Mdmx, COP1, Pirh2, ARF
      BP1/Mule, and CHIP) and a deubiquitinating enzyme, herpesvirus-associated
      ubiquitin-specific protease (HAUSP). In this article, we review the regulatory
      mechanism of p53 via ubiquitination and deubiquitination system and suggest the
      several possible therapeutic strategies of targeting HAUSP, a deubiquitinating
      enzyme for p53, for treating hematopoietic tumors.

PMID- 16596238
TI  - Association of XRCC1 gene polymorphisms with the susceptibility and chromosomal
      aberration of testicular germ cell tumors.
AB  - It is known that many genomic and genetic alterations caused by aging or
      environmental factors are responsible for cancer development and progression.
      XRCC1 is involved in the repair of DNA single-strand breaks formed by exposure to
      ionizing radiation and alkylating agents. The objective of this study was to
      investigate the association of genomic alterations and the susceptibility of
      testicular germ cell tumors with XRCC1 polymorphisms. Two polymorphisms of XRCC1,
      Arg194Trp and Arg399Gln, were genotyped in 83 patients with testicular germ cell
      tumors (TGCT) and 87 male controls. Allelic imbalances (AI) were evaluated using
      4 microsatellite markers in a subgroup of 50 patients. Patients with at least one
      Gln allele of the Arg399Gln polymorphism had an increased risk of TGCT than those
      with the Arg/Arg genotype (aOR=1.775, 95% CI=1.045-3.016, P=0.034). Furthermore,
      the increased risk associated with the Gln allele against the Arg homozygote was
      more strongly observed in patients with pure seminoma (aOR=2.242, 95% CI=1.149
      4.374, P=0.018) or with metastasis (aOR=2.481, 95% CI=1.267-4.862, P=0.008). In
      the Arg194Trp polymorphism, there was no significant difference in the genotype
      distribution between TGCT patients and the controls. In AI analysis, the
      frequency of AI was significantly higher in tumors with at least one Gln allele
      than those with the Arg/Arg genotype in D13S317 (P=0.010) and in a combination of
      4 markers (0.51+/-0.32 vs 0.32+/-28, P=0.028). Our results suggest that the Gln
      allele of the XRCC1 Arg399Gln polymorphism may genetically modify the development
      and progression of TGCT through genomic instability.

PMID- 16596239
TI  - Antisense telomerase RNA inhibits the growth of human glioma cells in vitro and
      in vivo.
AB  - Telomerase is implicated in the development of cellular immortality and
      oncogenesis. It has been shown that telomerase activity is considerably higher in
      the tissue of many different cancers than in normal tissue, and that the
      inhibition or downregulation of telomerase activity can prevent the malignant
      proliferation of tumor cells. Antisense oligonucleotides have been widely used in
      suppressing the expression of genes and, therefore, in the present research, we
      evaluated the effect of antisense human telomerase RNA (hTR) on glioma cell
      growth in vitro and in vivo. We showed that antisense hTR cDNA significantly
      inhibited TJ905 human glioma cell proliferation in vitro and tumor growth in
      vivo, as determined by MTT assay and by measuring the volume of glioma in nude
      mice. Consistent with these results, we found that telomerase activity and the
      mRNA levels of hTR and hTERT (human telomerase reverse transcriptase) expression
      were markedly decreased in tumor cells treated with antisense hTR cDNA, as
      assessed by TRAP (telomeric repeat amplification protocol) assay and RT-PCR
      (reverse transcription-polymerase chain reaction) analysis. Our study
      conclusively demonstrates that antisense hTR effectively inhibits the growth of
      human glioma cells in vitro and in vivo and, thus, may be potentially used for
      gene therapy of malignant gliomas and other cancers.

PMID- 16596240
TI  - Sequence-dependent interaction between cisplatin and histone deacetylase
      inhibitors in human oral squamous cell carcinoma cells.
AB  - Chemotherapeutic treatment with combinations of drugs is front-line therapy for
      many types of cancer. Combining drugs that target different signaling pathways
      often lessens adverse side-effects while increasing the efficacy of treatment and
      reducing patient morbidity. Histone deacetylase (HDAC) inhibitors represent a
      novel class of anti-neoplastic agents that act by promoting acetylation of core
      histones, leading in turn to the uncoiling of chromatin and activation of a
      variety of genes implicated in the regulation of cell survival, proliferation,
      differentiation, and apoptosis. A defined scheduling protocol is described by
      which HDAC inhibitors facilitate the cytotoxic effectiveness of cisplatin (CDDP)
      in the killing of carcinoma cells. An oral squamous cell carcinoma cell line (HSC
      3) was treated with sodium butyrate (NaB), suberoylanilide hydroxamic acid (SAHA)
      or MS-275 on the day of, the day before, or the day after addition of CDDP. The
      IC50 (48-h assay) value of 3.48 microg/ml CDDP could be lowered to 0.41 microg/ml
      CDDP when concurrently combined with an HDAC inhibitor (MS-275). The percentage
      of apoptosis by treatment with CDDP for 24 h, followed by NaB for an additional
      24 h without washing was significantly greater than that observed in the reverse
      order. Depending on the time of addition of HDAC inhibitors, CDDP-treated cells
      displayed varying degrees of apoptotic responses, indicating the critical nature
      of timing in the use of HDAC inhibitors. Interestingly, experiments suggested
      that cells arrested at the G1/S checkpoint by CDDP were more sensitive to
      subsequent treatment with an HDAC inhibitor. Moreover, these events were
      associated with an enhancement of reactive oxygen species (ROS) generation and
      caspase-3 activation by HDAC inhibitors. They raise the possibility that
      combining these agents may represent a novel anti-neoplastic strategy.

PMID- 16596241
TI  - Comparative integromics on Eph family.
AB  - EPHA1, EPHA2, EPHA3, EPHA4, EPHA5, EPHA6, EPHA7, EPHA8, EPHA10, EPHB1, EPHB2,
      EPHB3, EPHB4 and EPHB6 are EPH family receptors for Ephrin family ligands.
      Ephrin/EPH signaling pathway networks with the WNT signaling pathway during
      embryogenesis, tissue regeneration, and carcinogenesis. TCF/LEF-binding sites
      within the promoter region of human EPH family members were searched for by using
      bioinformatics and human intelligence. Because five TCF/LEF-binding sites were
      identified within the 5'-promoter region of the EPHA7 gene, comparative genomics
      analyses on EPHA7 orthologs were further performed. EPHA7-MANEA-FHL5 locus at
      human chromosome 6q16.1 and EPHA10-MANEAL-FHL3 locus at human chromosome 1p34.3
      were paralogous regions within the human genome. Human EPHA7 mRNA was expressed
      in embryonic stem (ES) cells, neural tissues, duodenal cancer and parathyroid
      tumors, while mouse Epha7 mRNA was expressed in fertilized egg, Rathke's pouche,
      visual cortex, pituitary gland, other neural tissues, pancreas, lung tumors and
      mammary tumors. The chimpanzee EPHA7 gene and cow Epha7 gene were identified
      within NW_107969.1 and AC155055.2 genome sequences, respectively. Five TCF/LEF
      binding sites within human EPHA7 promoter were conserved in the chimpanzee EPHA7
      promoter, and three TCF/LEF-binding sites in the cow Epha7 promoter, but none in
      the mouse Epha7 promoter. Primates and cow EPHA7 orthologs were identified as
      evolutionarily conserved targets of the WNT/beta-catenin signaling pathway.
      D6S1056 microsatellite marker within EPHA7 gene is deleted in prostate cancer.
      Deletion and/or promoter CpG hypermethylation could explain the EPHA7 down
      regulation in human tumors. EPHA7 is a target of systems medicine, especially in
      the fields of regenerative medicine and oncology.

PMID- 16596242
TI  - 18FDG PET in oncology: the best and the worst (Review).
AB  - The clinical added-value of 18F-fluoro-2-deoxy-D-glucose positron emission
      tomography (18FDG PET) in the management of oncology patients is increasingly
      documented. In the present review, we discuss both the benefits and the
      limitations of 18FDG PET in different cancers. Considering the literature data
      and our own experience, we also indicate the best clinical approach to optimize
      the use of metabolic imaging in oncology.

PMID- 16596243
TI  - Oxytocin synthesis within the normal and neoplastic breast: first evidence of a
      local peptide source.
AB  - The role of the neurohypophyseal peptide oxytocin (OT) and its receptor (OTR) in
      the breast has been described mainly in relation to breast feeding or to
      neoplastic growth regulation. We demonstrate here the presence of OT synthesis
      within the breast under both physiological and neoplastic conditions. In order to
      clarify whether normal epithelial and myoepithelial cells could synthesize OT,
      the two different cell types were separated using immunomagnetic technique after
      enzymatic digestion of breast specimens obtained during reductive mastoplasty.
      The freshly isolated cells as well as primary stabilized cultures derived from
      purified normal breast epithelial and myopithelial cells were then studied. Both
      epithelial and myoepithelial cells contained the mRNA for OT and OTR; however,
      only myoepithelial cells showed an effective OT synthesis and detectable peptide
      release in the culture medium. Moreover, OT expression was studied at mRNA and
      protein level in 10 human breast carcinoma cell lines. OT mRNA was present in
      half (5 out of 10) of the breast carcinoma cell lines tested, and OT was
      synthesized and released in the cell medium, irrespective of the estrogen
      receptor status of the different cell lines. However, in the two ER+ cell lines
      actively producing OT, such synthesis was significantly increased following
      estradiol (E2) treatment. These data altogether suggest the existence of a local
      OT source within the normal as well as within the neoplastic breast, and that
      such synthesis can be modulated by E2.

PMID- 16596244
TI  - Analysis of p53 mutations for a mutational signature in human intrahepatic
      cholangiocarcinoma.
AB  - Cholangiocarcinoma development may be related to cholangiocyte DNA damage from
      genotoxic compounds in bile. We have previously shown that human biliary tissue
      is exposed to genotoxic agents, as evidenced by the presence of DNA adducts.
      Establishing the presence of a 'mutational signature' in tumour suppressor genes
      from tumour tissue provides a means of linking cause and effect in human cancer.
      Inactivation of p53, known to have 'hot-spots' for particular chemical
      carcinogens, has previously been linked to human cholangiocarcinoma. However,
      previous p53 studies have focused on exons 5-8, potentially missing gene
      alterations at other sites. This study examined the putative link between
      environmental carcinogens and intrahepatic cholangiocarcinoma by analysing DNA
      from 31 patients for complete p53 mutational signatures, using single strand
      conformational polymorphism and polymerase chain reaction. All mutations found
      were compared to known p53 mutations in cholangiocarcinoma and to mutations
      induced by environmental mutagens, as described in p53 databases. Five non-silent
      p53 mutations were found, including three new frameshift mutations and two new
      intron mutations which have not previously been reported in cholangiocarcinoma.
      Two frameshifts were due to deletions and the third due to an insertion in exon
      5. There was no predominant mutational spectrum amongst the set of
      cholangiocarcinoma samples studied, or on combining these mutations with the
      dataset of known p53 mutations in cholangiocarcinoma. Several reasons may explain
      this, including lack of data outside exons 5-8, bias in mutation reporting, the
      involvement of mutations in non-coding regions or genes other than p53, or the
      possibility that there is no carcinogenic specific agent and therefore no
      signature.

PMID- 16596245
TI  - Dysregulated TGF-beta1-induced Smad signalling occurs as a result of defects in
      multiple components of the TGF-beta signalling pathway in human head and neck
      carcinoma cell lines.
AB  - This study examined Smad2- and Smad3-dependent transcription in 12 human head and
      neck squamous cell carcinoma (HNSCC) cell lines following treatment with
      transforming growth factor-beta1 (TGF-beta1). A markedly elevated level of TGF
      beta1-induced Smad3 signalling was observed in one cell line (H357), whilst four
      cell lines (BICR31, H314, BICR56, BICR19) demonstrated absence of Smad3-dependent
      transcription that correlated with loss of TGF-beta1 growth inhibition; TGF-beta1
      induced Smad2-dependent transcription was retained in two of these cell lines
      (H314, BICR31). Using transient expression of TGF-beta signalling components and
      a Smad3-dependent reporter assay, we show that BICR31 and H314 had defects of
      Smad4, BICR56 had abnormal TbetaR-II and BICR19 overexpressed Smad7. The results
      demonstrate that deregulated TGF-beta1-induced Smad signalling is common in HNSCC
      cell lines and can occur as a result of a variety of defects in the TGF-beta
      signal transduction pathway.

PMID- 16596246
TI  - Phenylhexyl isothiocyanate inhibits histone deacetylases and remodels chromatins
      to induce growth arrest in human leukemia cells.
AB  - Natural isothiocyanates, present in cruciferous vegetables and synthetic
      phenylhexyl isothiocyanate (PHI) are chemopreventive agents which act by blocking
      the initiation of carcinogen-induced tumors in rodents. We have demonstrated that
      isothiocyanates are also growth regulators, inhibiting cell cycle cdk activity
      and up-regulating inhibitor p21WAF1 (p21) in cancer cells. The up-stream
      mechanism to modulate cell cycle progression remained to be elucidated. Here, we
      have demonstrated that exposure of HL-60 leukemia cells to PHI induced G1 arrest
      and apoptosis. The hypothesis that PHI inhibits cell growth via chromatin
      remodeling was investigated. PHI mediates the complex cross talk between
      chromatin and DNA, and it was demonstrated for the first time as an inhibitor of
      histone deacetylases (HDAC). Thus, the HDAC activity in PHI-exposed HL-60 cells
      was reduced. Additionally, PHI reduced the expression of HDAC and increased the
      level of acetyl transferase p300, in favor of accumulation of acetylated
      histones. Within hours, global acetylation of histones was enhanced. PHI further
      mediated selective alterations of histone methylation, with a pattern consistent
      to the marks of transcription competent chromatins. The relationship between
      acetylated histones and p21 was examined by chromatin immunoprecipitation (ChIP)
      assay. Chromatins from cells exposed to PHI contained more p21 DNA in the
      precipitates of hyperacetylated histones, indicating more accessibility of
      transcription machinery to the p21 promoter after chromatin unfolding. The cell
      cycle inhibitors were activated as a result. In contrast to the PHI-induced
      apoptosis in HL-60 cells, which was mediated by caspase-9 up-regulation and bcl-2
      reduction, PHI did not induce significant apoptosis in the mononuclear cells from
      normal peripheral blood and bone marrow. The results revealed a potential
      selective effect of isothiocyanates to inhibit the growth of malignant cells.

PMID- 16596247
TI  - Defining high-risk individuals in a population-based molecular-epidemiological
      study of lung cancer.
AB  - Within the framework of the Liverpool Lung Project (LLP), population-based case
      control and prospective cohort studies are in progress to identify molecular and
      epidemiological risk factors and define populations and individuals most at risk
      of developing lung cancer. This report describes a strategy for selection of a
      high-risk population and further provides support for the inclusion of
      occupational and genetic risk factors in future models. Data from the case
      control study (256 incident cases and 314 population controls) were analysed to
      define a high-risk population. Detailed lifestyle and occupational information
      were collected during structured interviews. Models were constructed using
      conditional logistic regression and included terms for age, tobacco consumption
      and previous respiratory disease. Smoking duration was chosen as the most
      important predictor of lung cancer risk [>50 years (OR 15.65, 95% CI 6.10
      40.15)]. However, such a model would preclude younger individuals. Several
      combinations of previous respiratory disease were also considered, of which a
      history of bronchitis, emphysema or pneumonia (BEP) was the most significant (OR
      1.86, 95% CI 1.28-2.69). A high-risk subset (based on combinations of smoking
      duration and BEP) was identified, which have a 4.5-fold greater risk of
      developing lung cancer (OR 4.5, 95% CI 2.33-8.68). Future refinement of the risk
      model to include individuals occupationally exposed to asbestos and with the p21
      genotypes is discussed. There is real potential for environmental and genetic
      factors to improve on risk prediction and targeting of susceptible individuals
      beyond the traditional models based only on smoking and age. The development of a
      molecular-epidemiological model will inform the development of effective
      surveillance, early detection and chemoprevention strategies.

PMID- 16596248
TI  - Thymidylate synthase expression pattern, expression level and single nucleotide
      polymorphism are predictors for disease-free survival in patients of colorectal
      cancer treated with 5-fluorouracil.
AB  - Several variables associated to thymidylate synthase (TS), the biological target
      of 5-fluorouracil (5FU) have been studied for their possible role as predictors
      of the clinical outcome and response to chemotherapy in colorectal cancer (CRC)
      patients. The level of protein expression and the number of variable tandem
      repeats of a 28-bp sequence within the gene promoter have been proposed as
      predictive and/or prognostic factors with variable agreement, while consensus
      seems to be achieved with respect to the value of a single nucleotide
      polymorphism (SNP) described within this same region. More recently, an
      association between TS expression pattern and survival has been disclosed.
      Paraffin-embedded sections from 140 CRC patients were analyzed by immuno
      histochemistry (Mab TS106) for TS levels and expression pattern. Also, VNTR and
      SNP were determined by polymerase-chain reaction (PCR) and restriction-length
      fragment polymorphism (RFLP) in 123 and 112 patients, respectively. Cytoplasmic
      expression pattern tended to be associated to C SNP (p=0.06). Low TS expression
      levels, cytoplasmic expression pattern and C SNP arose as variables associated to
      longer progression-free survival (PFS) in patients treated with 5FU. Accordingly,
      patients having at least two favourable or unfavourable variables were classified
      respectively as 'low risk' and 'high risk', the former showing significantly
      longer PFS (p=0.0299). The possibility for designing a selection method for
      subsequent therapies is suggested on the basis of a probable combined effect of
      the above mentioned parameters but further studies in larger populations are
      needed to confirm these results.

PMID- 16596249
TI  - Chemokines in vascular pathology (review).
AB  - Clinical complications of atherosclerosis are major causes of morbidity and
      mortality in Western societies. Recent evidence suggests that formation of
      atherosclerotic lesions is an inflammatory process involving multiple molecular
      pathways. Chemokine-mediated mechanisms are potent regulators of such processes
      by orchestrating the interactions of inflammatory cellular components of the
      peripheral blood with cellular components of the arterial wall. The increasing
      evidence supporting the role of chemokine-pathways in atherosclerosis renders
      chemokine ligands and their receptors potential therapeutic targets. In the
      following review, we intend to highlight the special structural and functional
      features of each chemokine sub-family in respect to their role in atherosclerosis
      and discuss to what extent such knowledge could be applied in diagnostic,
      prognostic or therapeutic practices.

PMID- 16596250
TI  - Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr
      68 after cisplatin treatment of human ovarian cancer cells.
AB  - High-fidelity maintenance of genomic integrity in eukaryotes is ensured by cell
      cycle checkpoints and DNA repair. The checkpoint kinase, Chk2, has been
      implicated in both of these responses. In response to DNA damage, Chk2 is
      initially phosphorylated at Thr-68, which leads to its full activation. The fully
      activated Chk2 then phosphorylates downstream substrates of cell cycle control.
      However, the mechanism of inactivation of Chk2 is still unknown. Protein
      phosphatase type 2A (PP2A) plays an essential role in cell cycle regulation and
      induction of G2 arrest by a mechanism of phosphorylation/dephosphorylation with a
      variety of protein kinases. Data from our investigation provide evidence that, in
      response to cisplatin exposure, PP2A associates with Chk2 as a complex in cells
      and functions as a negative regulator of Chk2 activation by dephosphorylating p
      Chk2. Results from immunostaining and coimmunoprecipitation demonstrate that Chk2
      and PP2A can colocalize in cells, and the holoenzyme of PP2A (subunits A, B and
      C) coimmunoprecipitates with p-Chk2. Further, inhibition of PP2A by okadaic acid,
      an inhibitor of PP2A, and by small interfering RNA (siRNA) to PP2A results in
      enhanced Chk2 phosphorylation, implicating a direct enzyme-substrate
      relationship. An in vitro PP2A dephosphorylation assay shows that PP2A
      dephosphorylates p-Chk2 in a cell-free system. These findings suggest that the
      protein serine/threonine kinase, Chk2, is activated after cisplatin exposure and
      negatively regulated by a tightly associated protein serine/threonine
      phosphatase, PP2A.

PMID- 16596251
TI  - Identification and localization of adrenomedullin-storing cardiac mast cells.
AB  - Adrenomedullin (AM), a potent vasodilatory hypotensive peptide, is expressed in
      the heart, where it is known to play a protective action. Light-microscopy
      immunocytochemistry (ICC) demonstrated the presence of AM immunoreactivity not
      only in the coronary-vessel wall and ventricular myocytes of the human and rat
      heart, but also in sparse voluminous cells located in the perivascular space.
      These cells displayed the same location of toluidine blue-positive mast cells,
      and electron microscopy ICC showed AM-immunogold staining over the granules of
      rat cardiac mast cells. The incubation of rat left ventricle fragments with the
      mast-cell histamine releaser compound 48/80 evidenced groups of AM-positive cells
      undergoing degranulation and caused an increase of approximately 50% in the AM
      concentration in the incubation medium. Collectively, our findings provide
      evidence that at least a subset of cardiac mast cells are able to synthesize and
      store AM, and upon stimulation to release it near coronary arterioles and
      venules.

PMID- 16596252
TI  - E2F-1 is a critical modulator of cellular senescence in human cancer.
AB  - Senescence limits cellular proliferation, and therefore might be a mechanism
      which could suppress the progression of cancer. Herein we show that E2F1, a
      transcription factor essential to a cell cycle progress and a main target of
      tumor suppressor Rb, is a critical barrier for the induction of senescence. Human
      cancer cells transfected with siE2F1 were shown to express replicative senescence
      markers, in addition to yielding positive results upon SA-beta-Gal staining.
      Consistent with the notion of the critical role in senescence of E2F1, cells
      which overexpressed E2F1 proved to be immune to the induction of senescence.
      Importantly, it appears that E2F1 depletion-induced cancer cell senescence is not
      reliant on the integrity of either Rb or p53. Our results provide a molecular
      explanation for the selectivity with which senescence induction occurs, and also
      provides insights into the possibility of using E2F1 as a therapeutic target in
      the treatment of cancer.

PMID- 16596253
TI  - Efficient differentiation into skin cells of bone marrow cells recovered in a
      pellet after density gradient fractionation.
AB  - We had previously demonstrated the participation of whole bone marrow cells from
      adult mice in the reconstitution of skin, including the epidermis and hair
      follicles. To get an insight into cell populations that give rise to the
      epithelial components of the reconstituted skin, we fractionated bone marrow
      cells derived from green fluorescent protein-transgenic mice by density gradient.
      Unexpectedly, we found that a substantial amount of mononucleated cells
      (approximately 30%) was recovered in the pellet fraction and that the cells in
      the pellet fraction preferentially differentiated into epithelial components of
      skin, rather than the cells in the mononuclear cell fraction. The pellet fraction
      contained more CD45-negative (thus uncommitted to the hematopoietic cell lineage)
      cells than the mononuclear cell fraction. These results indicate that density
      gradient fractionation results in significant loss of specific progenitor cells
      into the usually discarded pellet fraction.

PMID- 16596254
TI  - Non-muscle myosin heavy chain IIA and IIB interact and co-localize in living
      cells: relevance for MYH9-related disease.
AB  - Myosins of class II constitute part of a superfamily of several classes of
      proteins expressed in almost all eukaryotic cell types. Differences in the heavy
      chains produce three isoforms of class II non-muscle myosins (A, B and C), which
      are widely distributed in most tissues and thought to be components of the cell
      motor systems, although specific functional roles are largely unknown. In
      particular, it is still a matter of debate whether they interact and have
      overlapping or distinct functions. This argument is relevant not only to cell
      physiology, but also to human pathology since mutations of the MYH9 gene encoding
      non-muscle myosin heavy chain II A (NMMHC-A) cause MYH9-related disease (MYH9
      RD), an autosomal dominant disorder characterized by platelet macrocytosis,
      thrombocytopenia and leukocyte inclusions, variably associated with sensorineural
      hearing loss, cataracts and/or glomerulonephritis. In this study, we report the
      results of yeast two-hybrid screening showing that the C-terminals of NMMHC-A and
      -B interact. This interaction was confirmed by immunoprecipitation in transfected
      COS-7 cells and in skin fibroblasts naturally expressing both isoforms. Moreover,
      our immunomorphological study revealed that isoforms A and B co-localize in
      fibroblasts, erythroblasts and kidney cells. These results suggest that isoforms
      A and B are strictly related molecules and support the hypothesis that their
      interrelationship could be involved both in the variability of clinical phenotype
      and selectivity of tissue damage of MYH9-RD.

PMID- 16596255
TI  - Development and evaluation of a colorimetric membrane-array method for the
      detection of circulating tumor cells in the peripheral blood of Taiwanese
      patients with colorectal cancer.
AB  - Early detection is the hallmark of successful cancer treatment. Evidence is
      accumulating that primary cancers begin shedding neoplastic cells in the
      circulation at an early stage. To date, a high-sensitivity and high-throughput
      method for the detection of circulating tumor cells (CTCs) is deficient. In this
      study, we have developed a high-sensitivity colorimetric membrane-array method to
      detect CTCs in the peripheral blood of colorectal cancer (CRC) patients as a
      potential diagnostic tool. Previously, we identified a set of 18 oligonucleotide
      clones, significantly overexpressed in CRC, which were synthesized and applied to
      a nylon membrane. Digoxigenin (DIG)-labeled cDNA were amplified by reverse
      transcriptase-polymerase chain reaction (RT-PCR) from the peripheral blood of 88
      Taiwanese CRC patients and 50 healthy subjects, and were then hybridized to the
      membrane-array. Hybridization signals were detected by color development.
      Meanwhile, blood samples were analyzed by real-time quantitative PCR (Q-PCR).
      Subsequently, both methods were compared regarding their correlation, sensitivity
      and specificity in the detection of CTCs by statistics. The results of membrane
      arrays were demonstrated to be closely related to that of Q-PCR (P<0.001). The
      sensitivity and specificity of membrane-arrays for the detection of CTCs were
      94.3% (95% CI, 86.4-102.2%) and 94% (95% CI, 85.9-102.1%), respectively.
      Moreover, the accuracy of membrane-arrays is higher than that of any one gene by
      Q-PCR. The detection rate of membrane-arrays was significantly associated with
      the depth of tumor invasion (P=0.002), the presence of lymph node metastasis
      (P=0.016), and TNM stage (P=0.005). The preliminary results indicated that the
      accuracy of membrane-arrays was sufficient to distinguish Taiwanese CRC patients
      from normal individuals with the advantages of time-saving, cost-effectiveness
      and high-throughput. Thus, the constructed colorimetric membrane-array could be a
      promising approach for the future detection of CTCs.

PMID- 16596256
TI  - Human RAB24, interestingly and predominantly distributed in the nuclei of COS-7
      cells, is colocalized with cyclophilin A and GABARAP.
AB  - As an atypical member of the Rab family, Rab24 has several attributes
      distinguishing this protein from the other members. Based on the yeast two-hybrid
      system, interaction between human RAB24 and two proteins, cyclophilin A (CyP-A)
      and gamma-aminobutyric acid type A receptor-associated protein (GABARAP), was
      detected and identified in COS-7 cells. Interestingly, RAB24 is predominantly
      localized in the nuclei of COS-7 cells, which is different from previous reports
      using other cell lines. RAB24 (D123I) can trigger the accumulation of
      intracellular inclusions, with small quantities of intranuclear inclusions in
      some cells. The GTPase activity of RAB24 and its two mutants was detected.

PMID- 16596257
TI  - Mutation in exon 7 of PTCH deregulates SHH/PTCH/SMO signaling: possible linkage
      to WNT.
AB  - The novel PTCH mutation and clinical manifestations within Gorlin syndrome family
      links PTCH haploinsufficiency and aberrant activation of the Wnt pathway. We
      report a family case with Gorlin syndrome, characterized by the usual phenotype
      features such as widespread basocellular tumors and craniofacial and bone
      malformations, but also including a less common appearance of craniopharyngioma.
      These clinical manifestations might be associated with a novel constitutional
      mutation of the PTCH gene, 1047insAGAA, which we found in exon 7. It changes the
      normal amino acid sequence leading to termination of the PTCH protein at exon 9.
      The analyzed tumors of the family show extensive loss of heterozygosity in the
      PTCH region, both basocellular and in particular craniopharyngioma, and in the
      latter a high expression of beta-catenin was detected. Our findings suggest
      involvement of the SHH/PTCH/SMO pathway in pathogenesis of the analyzed
      disorders, including its possible contribution to aberrant activation of the Wnt
      pathway in craniopharyngioma.

PMID- 16596258
TI  - Yes-associated protein (YAP65) in relation to Smad7 expression in human
      pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is characterized by multiple alterations
      in the TGF-beta signaling pathway. Yes-associated protein (YAP65) interacts with
      Smad7 thereby influencing TGF-beta signaling. In the present study, the
      expression of YAP65 in PDAC was analyzed in order to elucidate the potential role
      of this molecule in the pathogenesis of pancreatic cancer. YAP65 mRNA expression
      levels in human pancreatic tissue samples and cell lines were analyzed by
      Northern blotting and quantitative RT-PCR. Immunohistochemistry was carried out
      to localize and quantify YAP65 expression in relation to Smad7 expression and
      Smad4 mutations. The effects of TGF-beta1 on Smad7 and YAP65 mRNA expression were
      analyzed by quantitative RT-PCR. Enhanced expression of YAP65 mRNA was identified
      by Northern blotting and quantitative RT-PCR in PDAC in comparison to the normal
      pancreas (2.5-fold increase) and to chronic pancreatitis (1.3-fold increase). In
      the normal pancreas, YAP65 was absent in acinar cells, large ducts and islet
      cells, but exhibited moderate to strong immunoreactivity in centroacinar cells
      and ductules. Tubular complexes in CP and CP-like lesions in PDAC also exhibited
      strong staining. In contrast, weak to moderate YAP65 immunoreactivity was present
      in the cancer cells. There was no correlation between YAP65 immunostaining and
      Smad7 staining or Smad4 mutations in the cancer samples. TGF-beta1 strongly
      induced Smad7 mRNA in Colo-357 and in Panc-1 cells, but only slightly induced
      YAP65 mRNA in Colo-357 cells. In conclusion, YAP65 is expressed mainly in
      centroacinar and small ductal cells in the normal pancreas. In PDAC, YAP65 is
      present in tubular complexes and to a lesser extent in cancer cells. Together
      with the known function of YAP65 in different growth and differentiation
      regulating pathways, it is suggested that this gene plays a role in the normal
      and diseased pancreas.

PMID- 16596259
TI  - Genomic abnormalities in chronic lymphocytic leukemia influence gene expression
      by a gene dosage effect.
AB  - This work describes the identification and impact of somatic genomic
      abnormalities in human chronic lymphocytic leukemia (CLL). Using molecular
      cytogenetics (FISH) and G-banding cytogenetic analysis, chromosome abnormalities
      were detected in 37 of 46 (80.4%) CLL patients. 13q14 deletion was the most
      common finding followed by trisomy 12 and 11q22.3 deletion. 17p13 deletion was
      also detected as were several less frequent chromosome abnormalities. The
      presence of these abnormalities significantly influenced the period of treatment
      free survival as well as other clinical characteristics. In particular, CLL
      samples with trisomy 12 and 11q22.3 deletion were associated with shorter
      treatment-free survival. In order to identify the under-lying molecular
      differences among CLL subgroups with different chromosome abnormalities, gene
      expression profiling was performed on a custom DNA microarray consisting of
      10,000 human gene-specific oligonucleotides. A gene dosage effect was observed
      where the expression of genes at the genetic loci of the sites of the somatic
      genomic abnormality was altered in a fashion according to the type of genomic
      change. This phenomenon was particularly evident in CLL samples with trisomy 12
      and 17p13 deletion. Thus, this study demonstrates that genomic abnormalities
      influence gene expression in CLL by a dosage effect.

PMID- 16596260
TI  - The calcium-sensing receptor and vitamin D receptor expression in tertiary
      hyperparathyroidism.
AB  - The parathormone (PTH) production is controlled by calcium and vitamin D, which
      interact with the calcium-sensing receptor (CaSR) and vitamin D receptor (VDR),
      respectively. All of these elements control calcium homeostasis, which is crucial
      for many physiological processes. Thus, impairment of the upstream component of
      this system, e.g. a decrease of CaSR and/or VDR, could result in
      hyperparathyroidism (HPTH). Therefore, the aim of this study was to assess the
      expression of CaSR and VDR in a tertiary form of HPTH (T-HPTH). The study
      involved 19 T-HPTH patients qualified for parathyroidectomy and 21 control
      parathyroids harvested from multi-organ cadaver donors. The small fragments of
      harvested glands were homogenized and used for Western blot analysis, whereas the
      remaining tissues underwent routine hematoxylin-eosin staining or immunostaining
      for CaSR and VDR. Among 64 T-HPTH parathyroids, 58 revealed the morphology of
      benign hyperplasia, 2 were identified as adenoma and 4 were classified as normal;
      some glands displayed a mixed histological phenotype. Western blot analysis
      revealed a decrease of CaSR and VDR in hyperplasia and adenoma-derived samples.
      However, no correlation between the types of hyperplasia and receptor expression
      was observed. On the other hand, microscopic analysis of CaSR- and VDR
      immunostained sections revealed a highly differentiated and significantly
      decreased mean expression of both receptors, which correlated with parathyroid
      histology. The reason behind the impaired expression of CaSR and VDR in T-HPTH is
      unclear. It presumably results from constant parathyroid stimulation at the stage
      of S-HPTH, followed by further development of polyclonal autonomy. However, the
      verification of this thesis requires further study.

PMID- 16596261
TI  - Quantitative evaluation of partial deletions of the DAZ gene cluster.
AB  - Partial deletions of the DAZ gene cluster are thought to cause spermatogenesis
      impairment. The presence of homologous copies of this gene in the Y chromosome
      does not allow PCR to be used for the identification of this abnormality. Hence,
      sequence family variants (SFV), following amplification of sY581, sY587 and sY586
      and subsequent enzymatic digestion with Sau3A, DraI and TaqI, respectively, and
      the dual fiber fluorescence in situ hybridization (FISH) have been used to this
      aim. However, SFV is not always able to identify single DAZ gene copy deletions.
      We report a quantitative real-time PCR application to evaluate partial deletions
      of the DAZ gene cluster. To accomplish this, we designed a probe on exon 6 of the
      DAZ gene which is repeated 3 times in DAZ1, once in DAZ2 and DAZ3 and twice in
      DAZ4. Five normozoospermic healthy men (C1-C5) having 4 DAZ gene copies by SFV
      were selected. Fiber-FISH confirmed this outcome in C1-C4, but not in C5 who had
      an incomplete DAZ gene cluster. The men underwent then quantitative real-time PCR
      and C1 was arbitrarily selected as calibrator for the calculation of the DAZ gene
      signals because of the lowest variation in the threshold cycles. Real-time PCR
      identified 7.2+/-0.05 signals in C2-C4 and 5.4+/-0.05 signals in C5. The overall
      coefficient of variation was 1.4+/-0.2%. The loss of two signals in this subject
      may relate to a deletion of both DAZ2 and DAZ3 or of DAZ4 gene. Since SFV showed
      clearly the presence of DAZ2, it may be hypothesized that C5 lacks DAZ4. In
      conclusion, these data suggested that quantitative real-time PCR seems to be an
      effective and reproducible technique that can be used to study the DAZ gene
      cluster. In addition, the probe chosen for this approach may give indication on
      the DAZ gene copy deleted.

PMID- 16596262
TI  - Polymorphism in ABCA1 influences CSF 24S-hydroxycholesterol levels but is not a
      major risk factor of Alzheimer's disease.
AB  - The ATP-binding cassette transporter A1 (ABCA1) mediates reverse cholesterol
      transport, polymorphisms have been shown to influence the levels of cholesterol
      and of HDL and the risk of coronary artery disease. Since altered cholesterol
      metabolism is also involved in Alzheimer's disease (AD), the effects of two ABCA1
      polymorphisms (G-395C promoter polymorphism (rs 2246293) and exonic R219K) on the
      risk of AD in 241 AD patients and 294 non-demented controls, and on CSF
      cholesterol and 24S-hydroxycholesterol in 74 AD patients and 42 non-demented
      controls were investigated. None of the investigated ABCA1 polymorphisms
      influenced the risk of AD. However, the ABCA1 G-395C polymorphism influenced CSF
      levels of 24S-hydroxycholesterol, but not of cholesterol, whereas the R219K
      influenced neither CSF levels of 24S-hydroxycholesterol nor cholesterol. Our data
      support the observation that ABCA1 polymorphisms influence cholesterol metabolism
      of the brain, but might not act as a major risk factor in AD.

PMID- 16596263
TI  - CER1 is a common target of WNT and NODAL signaling pathways in human embryonic
      stem cells.
AB  - Nodal and BMP signaling pathways network with WNT signaling pathway during
      embryogenesis and carcinogenesis. CER1 (Cerberus 1) and GREM3 (CKTSF1B3 or CER2)
      inhibit NODAL signaling through ACVR1B (ALK4) or ACVR1C (ALK7) to SMAD2 or SMAD3.
      GREM1 (CKTSF1B1) inhibits BMP signaling through BMPR1A (ALK3), BMPR1B (ALK6) or
      ACVR1 (ALK2) to SMAD1, SMAD5 or SMAD8. CER1, GREM1 and GREM3 are DAN domain
      (DAND) family members; however, transcriptional regulation of DAND family members
      by canonical WNT signaling pathway remains unclear. We searched for the TCF/LEF
      binding site within the promoter region of DAND family genes, including CER1,
      GREM1, GREM2, GREM3 and NBL1. Because triple TCF/LEF-binding sites were
      identified within human CER1 promoter by using bioinformatics and human
      intelligence, comparative genomics analyses on CER1 orthologs were further
      performed. Chimpanzee CER1 gene, encoding 267-amino-acid protein, was identified
      within NW_111298.1 genome sequence. XM_528542.1 was not a correct coding sequence
      for chimpanzee CER1. Primate CER1 orthologs were significantly divergent from
      rodent Cer1 orthologs. Three TCF/LEF-binding sites within human CER1 promoter
      were conserved in chimpanzee CER1 promoter, two in cow and dog Cer1 promoters,
      but not in rodent Cer1 promoters. Binding sites for NODAL signaling effectors,
      SMAD3/SMAD4 and FOXH1, were also conserved among human, chimpanzee, cow and dog
      CER1 promoters. CER1 orthologs were evolutionarily conserved target of WNT and
      NODAL signaling pathways in non-rodent mammals. Human CER1 mRNA was expressed in
      embryonic stem (ES) cells in the undifferentiated state and in the early
      endodermal lineage. CER1 upregulation in human ES cells leads to Nodal signaling
      inhibition associated with differentiation of human ES cells. Primate CER1
      orthologs, playing a pivotal role during early embryogenesis, underwent protein
      evolution as well as promoter evolution. These facts indicate that molecular
      evolution of CER1 orthologs contributes to the significantly divergent scenarios
      of early embryogenesis in primates and rodents.

PMID- 16596264
TI  - Gene transduction of tristetraprolin or its active domain reduces TNF-alpha
      production by Jurkat T cells.
AB  - Tristetraprolin (TTP) is a physiological regulator of tumor necrosis factor (TNF)
      alpha production. It destabilizes TNF-alpha mRNA by binding to the AU-rich
      element located in the 3' region of TNF-alpha mRNA. We wished to determine how
      transducing the TTP gene or its fragment gene encoding its biological active
      site, the tandem zinc finger (TZF) domain, affects TNF-alpha production, cell
      viability and growth of Jurkat T cells. Jurkat T cells were transduced with
      either the TTP or the TZF gene using retrovirus vectors. Cell growth and
      apoptosis was analyzed. Expression of genes before or after appropriate stimuli
      was measured by real-time PCR. In addition, production of the TNF-alpha protein
      was measured by enzyme immunoassay. The transduction of either gene reduced TNF
      alpha mRNA levels under unstimulated conditions, and reduced the response to
      phytohemagglutinin stimulation. Production of TNF-alpha protein upon stimulation
      was also decreased in TTP/TZF-transduced cells. Transduction of either gene also
      affected the expression of granulocyte-macrophage colony-stimulating factor mRNA
      in a similar fashion, but not that of c-myc. The growth rate of TTP-transduced
      Jurkat T cells tended to be slower than that of TZF- or mock-transduced cells.
      TTP-transduced cells were more susceptible to campthothecin-induced apoptosis
      than others. Our results indicate that either TTP or TZF gene transduction using
      retrovirus vectors can reduce the production of TNF-alpha in Jurkat T cells
      although some differences were noted between TTP and TZF in cell growth and
      occurrence of apoptosis. These results suggest that TTP may be a potential target
      for new therapies against RA.

PMID- 16596265
TI  - Anandamide-induced apoptosis in Chang liver cells involves ceramide and JNK/AP-1
      pathway.
AB  - In the present study we demonstrate that anandamide, the most important
      endogenous cannabinoid, markedly induced apoptosis in Chang liver cells, an
      immortalized non-tumor cell line derived from normal liver tissue, while it
      induced only modest effects in a number of hepatoma cell lines. The apoptotic
      effect was reduced by methyl-beta-cyclodextrin, a membrane cholesterol depletor,
      suggesting an interaction between anandamide and the membrane microdomains named
      lipid rafts. Anandamide effects were mediated by the production of ceramide, as
      demonstrated by experiments performed with the sphingomyelinase inhibitor,
      desipramine, or with the sphingomyelinase activator, melittin. This conclusion
      was confirmed by the observation that exogenous C2-ceramide induced a remarkable
      apoptotic effect in the same cells. Anandamide-induced apoptosis in Chang liver
      cells involved oxidative stress and activation of p38/JNK pathway, which was
      accompanied by a remarkable increase in AP-1 DNA-binding activity. Moreover, the
      levels of both c-Jun and JunB, two components of the AP-1 complex, and those of
      FasL and Bim, two transcriptional targets of AP-1, also increased during
      anandamide treatment. In addition, anandamide increased the level of Bax and
      caused degradation of full-length Bid with the production of the active truncated
      form. These effects were accompanied by dissipation of mitochondrial
      transmembrane potential with the consequent activation of both caspase-3 and
      caspase-6. On the contrary, in hepatoma cells, anandamide did not induce
      apoptotic effects and it was not possible to observe any increase in p38/JNK
      pathway and AP-1 activity after drug treatment. Our results suggest that the
      induction of cell death in non-tumor Chang liver cells by anandamide was mediated
      by ceramide, JNK and AP-1 and was dependent on the activation of both the
      extrinsic and intrinsic pathways of apoptosis.

PMID- 16596266
TI  - Apolipoprotein-E modulates the cytotoxic effect of beta-amyloid on rat brain
      endothelium in an isoform-dependent specific manner.
AB  - Several studies support the hypothesis that apolipoprotein-E (ApoE) acts as a
      pathological chaperone protein that promotes the beta-plated sheet conformation
      of beta-amyloid (Abeta) peptides into amyloid fibers. In vitro evidence is also
      available that ApoE inhibits the neurotoxic effect of Abeta in an allele-specific
      manner (E2 > or = E3 > E4). We have recently shown that Abeta peptides exert a
      time- and concentration-dependent toxic effect on rat neuromicrovascular
      endothelial cells (NECs), and this study aimed to ascertain whether ApoE isoforms
      are able to modulate this effect. ApoE2 and ApoE4 decreased and increased,
      respectively, the cytotoxic effect of Abeta(1-40) and Abeta(1-42) on NECs, as
      evaluated by their survival and viability rates. The toxic effect of both Abeta
      peptides and ApoE4 was associated with the rise in the necrosis rate of NECs
      within a 24-h incubation period. Moreover, ApoE2 prevented and ApoE4 magnified
      the inhibitory effect of Abeta on the capability of NECs cultured on Matrigel to
      form a capillary-like network. The opposite effects of ApoE isoforms could be due
      to their different interactions with the C-terminal domain of Abeta. ApoE2, at
      variance with ApoE4, is thought to form sodium dodecyl sulphate-stable complexes
      with Abeta and, as a consequence, it could block the interactions of the non
      fibrillar Abeta peptide with the plasma membrane, Abeta peptide aggregation and
      the ensuing cytotoxicity. Collectively, our findings confirm the view that ApoE
      plays a relevant role in the pathogenesis of Alzheimer's disease.

PMID- 16596267
TI  - Antibody to hepatitis B core antigen is associated with the development of
      hepatocellular carcinoma in hepatitis C virus-infected persons: a 12-year
      prospective study.
AB  - Several studies have reported that antibody to hepatitis B core antigen (anti
      HBc) positivity may influence the development of hepatocellular carcinoma (HCC)
      in chronic hepatitis C patients, but the evidence is still not conclusive. In
      this study, we examined whether the presence of anti-HBc positive was associated
      with the development of HCC in hepatitis C virus (HCV)-infected subjects among
      the residents in an HCV hyperepidemic area who were followed up for 12 years. In
      an HCV hyperendemic area (positive rate of anti-HCV: 23.4%), 509 residents were
      examined by health screening in 1990. After 12 years of follow-up, we evaluated
      the risk factors for HCC. The incidence of HCC was compared between anti-HBc
      positive and anti-HBc negative subjects after 12 years of prospective
      observation. Univariate and multivariate analyses were conducted to determine
      risk factors for the development of HCC. The incidence of HCC was significantly
      higher in the anti-HBc positive group (13 subjects) than in the anti-HBc negative
      group (0 subjects) (P=0.012). Multivariate analysis identified positivity for
      anti-HBc and HCV RNA, history of icterus, and female gender as independent
      determinants of the development of HCC. Our findings provide clear evidence in a
      prospective study that presence of anti-HBc, that is, past hepatitis B virus
      (HBV) infection, is a risk factor for the development of HCC in HCV-infected
      people.

PMID- 16596268
TI  - Synthetic peptide F2A4-K-NS mimics fibroblast growth factor-2 in vitro and is
      angiogenic in vivo.
AB  - A multi-domain synthetic peptide, F2A4-K-NS, mimicked the action of recombinant
      human FGF-2 (rhFGF-2) in vitro and in an in vivo model of angiogenesis. Like
      rhFGF-2, F2A4-K-NS was quantitatively shown to bind to FGF receptors in a cell
      free receptor binding assay using a chimeric FGFR1 (IIIc)/Fc as monitored by
      surface plasmon resonance (SPR), and also shown to bind to heparin using
      biotinylated low-molecular weight heparin in a similar SPR assay. In vitro, F2A4
      K-NS triggered signal transduction as monitored by the stimulation of ERK1/2
      phosphorylation in human umbilical cord endothelial cells. In cell based assays,
      it increased cell migration, cell proliferation, and gelatinase secretion;
      endpoints associated with FGF-2 stimulation. Furthermore, these in vitro effects
      were mediated with quantities of F2A4-K-NS that were similar to those of rhFGF-2.
      In vivo, F2A4-K-NS was angiogenic at doses of 40 and 400 ng/implant in a
      subcutaneous implant assay as determined by morphologic scoring, hemoglobin
      content, and histology. These results support the hypothesis that F2A4-K-NS is a
      mimetic of FGF-2 that can substitute for FGF-2 in vitro and in vivo. A synthetic
      mimetic of FGF-2, such as F2A4-K-NS, could be a useful tool in studying
      mechanisms of cell activation and potentially in various therapeutic
      applications.

PMID- 16596270
TI  - Identification of a unique set of genes altered during cell-cell contact in an in
      vitro model of prostate cancer bone metastasis.
AB  - The interaction between prostate cancer cells and bone marrow stromal cells
      (BMSC) is critical for survival and proliferation of metastatic cancer cells in
      the bone microenvironment. In order to study molecular mechanisms of prostate
      cancer bone metastasis, we established a novel heterotypic co-culture system, in
      which the role of direct cell-cell contact between prostate cancer cells and BMSC
      in addition to soluble factors can be analyzed. Using both bi-compartmental
      (insert) system and heterotypic (contact) system, we identified gene expression
      profiles of interaction between prostate cancer and bone cells. Analysis of
      differential gene expressions in these two co-culture systems revealed three
      distinctive sets of genes: 1) genes that were modified only by soluble factors;
      2) genes that were regulated by both soluble factors and physical contact; and 3)
      genes that were altered only by physical contact. The last group consisted of
      specific set of genes including collagen III, IV, X, XII, integrin alpha1,
      alpha2, MMP-2, MMP-9, uPA, biglycan, osteopontin and raf-1 in PC3, and collagen
      VIII, IX, BMP6, TGFbeta1, Smad6 and Twist in BMSC. Among genes that were modified
      by both soluble factors and physical contact, the gene expression was affected in
      the same direction (such as MKK4) or in the opposite direction (such as TGFbeta
      receptor 3). Overall, this suggests that heterotypic cell-cell contact may act as
      an independent factor affecting the progression of bone metastasis.

PMID- 16596269
TI  - Caspase-1 as a radio- and chemo-sensitiser in vitro and in vivo.
AB  - The cytotoxic effect of anticancer drugs has been shown to involve induction of
      apoptosis. This observation raises the possibility that factors affecting caspase
      activation might be important determinants of anticancer drug sensitivity.
      Ectopic expression of caspase-1 has been shown to trigger apoptosis. However, the
      role of caspase-1 in apoptosis is now considered as minor compared to other
      caspases. In patients, high levels of caspase-1 expression may be associated with
      spontaneous regression in neuroblastomas and with a good clinical response to
      chemotherapy in acute myeloid leukemia and osteosarcoma. In experimental
      therapeutics for cancer, caspase-1 has been related to some anticancer activity.
      These observations led us to examine the effect of over-expression on the
      response to chemotherapy and radiotherapy in vitro and in vivo. Caspase-1
      expression mediated by an adenoviral vector was able to kill directly cells and
      to sensitise the remaining cells to cisplatin or gamma-radiation in vitro. In
      HeLa cells stably transfected with caspase-1, sensitisation to cisplatin was due
      to an amplification of the cisplatin-induced mitochondrial apoptotic pathway
      activation. Caspase-1 mediated sensitisation to cisplatin and gamma-radiation was
      also observed in vivo. Altogether, we conclude that caspase-1 can act as a radio-
      and chemo-sensitiser, in vitro and in vivo.

PMID- 16596272
TI  - Accumulation of steroidogenic acute regulatory protein mRNA, and decrease in the
      secretory and proliferative activity of rat adrenocortical cells in the presence
      of proteasome inhibitors.
AB  - Sporadic findings indicate that proteolysis may affect steroid secretion in rat
      ovary granulosa cells. We examined the effects of the proteasome inhibitors MG115
      and MG101 on the in vitro secretion and growth of rat adrenocortical cells. MG115
      and/or MG101 decreased within 120 min the aldosterone and corticosterone
      secretion from freshly dispersed zona glomerulosa and zona fasciculata
      reticularis (ZF/R) cells. After a 24-h incubation MG115 alone or with MG101
      lowered corticosterone production and enhanced proliferation rate of cultured
      ZF/R cells, while MG101 was per se ineffective. Real-time polymerase chain
      reaction demonstrated that MG101 decreased steroidogenic acute regulatory protein
      (StAR) mRNA in cultured cells. MG115 was per se ineffective, but when added
      together with MG101 evoked a marked rise in StAR mRNA content. In light of the
      present findings, we conclude that i) protein breakdown by proteasomes is
      required for the maintenance of a normal secretory and proliferative activity of
      freshly dispersed or cultured rat adrenocortical cells; and ii) in long-term
      experiments, great caution must be taken in correlating StAR mRNA content and
      steroidogenic capacity.

PMID- 16596271
TI  - Relationship between the proliferative capability of hepatocytes and the
      intrahepatic expression of hepatocyte growth factor and c-Met in the course of
      cirrhosis development in rats.
AB  - Liver cirrhosis is the fatal end stage of various chronic liver diseases. One of
      the most important causes of liver cirrhosis appears to be an impaired
      proliferative capability of hepatocytes caused by continuous hepatic damage.
      Hepatocyte growth factor (HGF) and its specific receptor, c-Met, play a pivotal
      role in hepatocyte proliferation. However, the relationship between the
      proliferative capability of hepatocytes and the intrahepatic expression of HGF
      and c-Met during the course of cirrhosis development has not been studied fully.
      In the present study, liver cirrhosis was produced in rats by intraperitoneally
      administering dimethylnitrosamine (DMN) and intrahepatic expression levels of HGF
      and c-Met were quantitatively estimated using a real-time reverse transcription
      polymerase chain reaction (RT-PCR) method. Histological examination of liver
      sections and biochemical estimation of serum levels of transaminase revealed that
      the degree of hepatocyte destruction was elevated gradually during cirrhosis
      development in the DMN-induced rat cirrhosis model. The proliferative capability
      of hepatocytes estimated immunohistochemically by proliferating cell nuclear
      antigen staining was markedly increased at an early stage of cirrhosis
      development. However, it was gradually decreased thereafter and suppressed
      substantially at the time of cirrhosis manifestation. Intrahepatic HGF expression
      was also increased significantly during the course of cirrhosis development but
      decreased significantly at the time of cirrhosis manifestation. Conversely, there
      was a tendency for the intrahepatic expression of c-Met to decrease from an early
      stage of cirrhosis development and intrahepatic c-Met expression was decreased
      significantly at the time of cirrhosis manifestation. These results suggest that
      the highly proliferative capability of hepatocytes at an early stage of cirrhosis
      development is induced by increased intrahepatic HGF expression. However, both
      HGF and c-Met expression levels in the liver are decreased significantly there
      after. Accordingly, the proliferative capability of hepatocytes is severely
      impaired and extracellular matrix components are deposited to retrieve space lost
      by the destruction of hepatic parenchyma, resulting in the establishment of liver
      cirrhosis.

PMID- 16596273
TI  - Deletion of the kinase domain from death-associated protein kinase enhances
      spatial memory in mice.
AB  - Death-associated protein kinase (DAPK) is a Ca2+/calmodulin-dependent
      serine/threonine kinase that is thought to mediate apoptosis. DAPK is highly
      expressed in hippocampal neurons which are essential elements for memory
      formation. To examine if DAPK is implicated in spatial learning and memory, both
      wild-type and DAPK-mutant mice were subjected to Morris water maze tests. DAPK
      mutant mice were generated by deleting 74 amino acids from the catalytic kinase
      domain of DAPK, and were used to investigate roles of the DAPK kinase domain in
      regulating spatial memory. Both mutant and wild-type mice were able to learn the
      water maze tasks to locate a hidden escape platform. In the first probe test,
      mutant mice showed a more precise memory for platform position compared to wild
      type mice. In the reversal training in which the platform was located opposite
      from the original position, DAPK-mutant mice exhibited superior spatial learning
      compared to wild-type mice. DAPK-mutant mice also showed a more precise memory
      than their wild-type littermates in the probe trial of reversal test. Thus, the
      present results revealed crucial implications of DAPK in regulating spatial
      memory in mice.

PMID- 16596274
TI  - Increased expression of membrane TNF-alpha on activated peripheral CD8+ T cells
      in systemic lupus erythematosus.
AB  - Membrane TNF-alpha is a precursor form of soluble TNF-alpha and exerts pro
      inflammatory functions in a cell-to-cell contact manner. We showed that membrane
      TNF-alpha is induced upon activation on the cell surface of CD4+ T cells and CD8+
      T cells. In patients with systemic lupus erythematosus (SLE), the percentage of
      membrane TNF-alpha-bearing CD8+ T cells (41.5+/-12.3%) was significantly higher
      compared with those of healthy controls (26.7+/-3.9%) (p=0.007) or patients with
      rheumatoid arthritis (29.8+/-15.4%) (p=0.038). Membrane TNF-alpha-bearing CD8+ T
      cells from SLE patients displayed cytotoxic activity against L929 cells. It is
      possible that membrane TNF-alpha may be involved in the increased apoptosis and
      the generation of autoantigens in SLE.

PMID- 16596275
TI  - Serum cytokine concentrations and acute graft-versus-host disease after
      allogeneic peripheral blood stem cell transplantation: concurrent measurement of
      ten cytokines and their respective ratios using cytometric bead array.
AB  - Both inflammatory and anti-inflammatory cytokines have been reported to be
      associated with acute graft-versus-host disease (aGVHD). However, their role and
      possible mutual interactions during aGVHD are not well understood. Eight patients
      with aGVHD and eight without who had undergone allogeneic HLA-identical
      peripheral blood stem cell transplantation were studied. The patients had no
      other complications known to affect serum concentration of cytokines, including
      infection. Serum concentrations of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10,
      IL-12p70, TNF-alpha and IFN-gamma were concurrently measured by a new technique,
      the cytometric bead array (CBA). We found that serum concentrations of IL-5, IL-6
      and IL-10 were significantly higher in patients with aGVHD than in patients
      without it. By ratiometric analysis, the ratios of IL-5/IL-2, IL-5/IL-4, IL-6/IL
      4 in patients with aGVHD were increased compared to the patients with no evidence
      of aGVHD. ROC analysis demonstrated that the ratio of IL-5/IL-4 was the most
      sensitive parameter associated with aGVHD. The second best marker of aGVHD was
      increased IL-5 concentration. Thus, our results indicate that the ratio of a
      particular cytokine/cytokine could be a potential diagnostic marker for aGVHD,
      more sensitive that the serum level of a given cytokine. This observation is
      consistent with a cross-talk among some cytokines and their possible interactions
      via respective receptors on cytokine-producing cells; these interactions may play
      an important role in pathogenesis of aGVHD. Further studies including a large
      number of patients and concurrent measurement of a variety of cytokines are
      needed to fully assess the diagnostic value of the cytokine ratiometric analysis.
      The CBA methodology provides a convenient and useful tool in such studies.

PMID- 16596276
TI  - Tumour necrosis factor-alpha: prognostic role and relationship with interleukin-8
      and endothelin-1 in non-small cell lung cancer.
AB  - Cytokines mediate numerous physiological and immune reactions, which are
      manifested in various biological effects, including tumouricidal activity. We
      evaluated the expression of the pleiotropic cytokine, tumour necrosis factor
      alpha (TNF-alpha), by competitive PCR technique in 47 non-small cell lung cancer
      (NSCLC) cases and the impact of TNF-alpha on their clinical behaviour. Using
      univariate analysis, our study demonstrated a positive correlation between high
      TNF-alpha expression and favourable prognosis in NSCLC in terms of overall
      survival and disease free interval (p=0.03 and 0.04, respectively) and TNF-alpha
      maintained its independent role in multivariate analysis. TNF-alpha can stimulate
      the expression of many molecules, including interleukin-8 (IL-8) and endothelin-1
      (ET-1); in our study, the expression of TNF-alpha was significantly associated
      with high IL-8 mRNA levels (p=0.008) and ET-1 mRNA positivity (p=0.03). We
      suggested that TNF-alpha can induce ET-1 mRNA expression in NSCLC, similarly to
      IL-8 expression. Our study may also contribute to advancing the knowledge of the
      molecular relationship between cytokines and endothelial functions in NSCLC.

PMID- 16596278
TI  - Amelioration of liver fibrogenesis by dual inhibition of PDGF and TGF-beta with a
      combination of imatinib mesylate and ACE inhibitor in rats.
AB  - Both platelet-derived growth factor (PDGF) and transforming growth factor-beta
      (TGF-beta) are known to be pivotal cytokines in liver fibrosis development. The
      aim of our current study was to elucidate the effects of dual inhibition of PDGF
      and TGF-beta by combination of the clinically used imatinib mesylate (STI-571)
      and perindopril (an ACE-inhibitor; ACE-I), respectively, on ongoing liver
      fibrosis development in rats. The effects of STI-571 and ACE-I at clinically
      comparable low doses were examined in a rat model of CCl4-induced liver
      fibrogenesis. Treatment with both STI-571 and ACE-I inhibited liver fibrogenesis
      and suppressed activation of hepatic stellate cells (HSCs). Administration of
      both agents exerted a more potent inhibitory effect than administration of either
      single agent. Our in vitro study demonstrated that STI-571 and ACE-I suppressed
      PDGF receptor (PDGFR) phosphorylation and TGF-beta expression in activated HSCs,
      respectively. Dual suppression of PDGF and TGF-beta with a combination of
      clinically comparable low doses of STI-571 and ACE-I exerted a significant
      inhibitory effect on ongoing liver fibrosis development. Since both agents are
      widely used in clinical practice, this combination therapy may provide a new
      strategy against liver fibrosis in the future.

PMID- 16596277
TI  - STI571 (Glivec) induces cell death in the gastrointestinal stromal tumor cell
      line, GIST-T1, via endoplasmic reticulum stress response.
AB  - STI571 is a specific inhibitor of tyrosine kinases, such as BCR-ABL, platelet
      derived growth factor receptor, and c-KIT, and has recently been approved for the
      treatment of chronic myeloid leukemia and gastrointestinal stromal tumors
      (GISTs). This study demonstrated that STI571 induces cell death in the
      gastrointestinal stromal tumor cell line, GIST-T1. In these cells, STI571 induced
      pro-caspase-12 or pro-caspase-7 cleavage and it affected caspase-3 activity and
      induced the endoplasmic reticulum (ER)-resident chaperone, glucose-regulated
      protein 78. The STI571-induced cell death was blocked by the protein synthesis
      inhibitor, cycloheximide. Together, these results suggest that STI571 induces
      cell death in GIST-T1 cells, at least in part, via the ER stress response.

PMID- 16596279
TI  - In vitro and in vivo immunomodulating activities of Shoyu polysaccharides from
      soy sauce.
AB  - We investigated the effects of Shoyu polysaccharides (SPS) prepared from soy
      sauce on immune functions in mice. SPS enhanced the consumption of glucose by
      peritoneal macrophages in vitro. In addition, oral administration of SPS to 6
      week-old male BALB/c mice for 2 weeks at a dose of 3.0 mg/day increased the
      capacity of peritoneal macrophages to consume glucose as compared to control
      mice. We observed the regulatory effect of SPS on the balance of Th1/Th2 cell
      responses in mice. In splenic lymphocytes stimulated with Con A in vitro, SPS
      significantly suppressed the production of IL-4 and enhanced that of IFN-gamma.
      Furthermore, in mice treated with SPS at 3.0 mg per day for 2 weeks, the balance
      of Th1/Th2 cell responses was shifted to predominantly Th1 cell responses. These
      findings suggest that SPS effectively enhanced both macrophage and lymphocyte
      function in vitro and in vivo, and soy sauce would be a potentially promising
      food for enhancing host defenses.

PMID- 16596280
TI  - CD4+ T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of
      Graves' ophthalmopathy.
AB  - Graves' ophthalmopathy (GO) is considered to be an organ-specific autoimmune
      disease. However, the pathogenesis of GO is incompletely understood at the
      present time. To clarify the immunological differences between newly diagnosed GO
      and Graves' disease (GD) without ophthalmopathy or healthy controls (HC), we
      examined T-cell profile and the Th1/Th2 profile cell balance in GO (n=20), GD
      (n=20) and HC (n=20) using flow cytometry. We also assessed the influence of
      methimazole on the immunocyte profiles in patients with GO and GD and analyzed
      the relationship of the immunologic changes with CAS, FT3, FT4, TRAb, TMA and TGA
      among the three investigated groups. We report in this study that: 1) The
      percentage of CD4+ T cells and the ratio of CD4+/CD8+ cells were higher, but the
      population of CD8+ T cells was lower in both GO and GD than those of HC (P<0.05);
      2) The percentage of CD8-/IFNgamma+ T cells (Th1) and the ratio of CD8-/IFNgamma+
      to CD8-/IL-4+ T cells (Th1/Th2) in GO were considerably higher as compared to
      those in GD and HC (P<0.05). On the contrary, the population of Th1 cells, as
      well as the ratio of Th1/Th2 cells, was lower in GD than that of GO and HC
      (P<0.05); 3) There were no significant differences in T-cell profile and the
      Th1/Th2 cell balance in either GO or GD patients before and after methimazole
      treatment; 4) There was a positive correlation of Th1 cell percentage and the
      Th1/Th2 cell ratio with the clinical activity score (CAS) in GO (P<0.05), whereas
      CAS in GO had no correlation with the T-cell profile, the percentage of Th2
      cells, and TRAb (P>0.05); 5) T-cell subset and the ratio of Th1/Th2 cells did not
      correlate significantly with FT3, FT4, TRAb, TMA, or TGA in GO and GD (P>0.05).
      Finally, 6) there were no statistical differences in TRAb, TMA, and TGA between
      early GO and GD without ophthalmopathy (P>0.05). Collectively, these results
      indicate that the balance of Th1/Th2 in GO shifts to Th1 dominance and that the
      cellular immune responses mediated by the Th1-type CD4+ cells might play a
      dominant role in the pathogenesis of GO, and thus suggest that the Th1 cell
      percentage and the ratio of Th1/Th2 cell subsets may be potentially utilized as
      clinical parameters for disease activity, for monitoring the effectiveness of
      immunosuppressive treatment, or for developing immunospecific forms of therapy
      for Graves' ophthalmopathy.

PMID- 16596281
TI  - Abnormal DNA end-joining activity in human head and neck cancer.
AB  - In human cells, DNA double-strand breaks (DSBs) are repaired primarily by the DNA
      end-joining (EJ) process and thus, abnormal DNA EJ activities lead to an
      accumulation of mutations and/or aneuploidy, resulting in genetic instability of
      cells. Since genetic instability is the hallmark of cancer cells, we studied the
      DNA EJ activities of normal, non-malignant immortalized and malignant human
      epithelial cells to investigate the association between DNA EJ and
      carcinogenesis. We found a significant diminution of precise (error-free) DNA EJ
      activities in non-malignant immortalized human oral keratinocytes (HOK-16B) and
      human head and neck squamous cell carcinoma (HNSCC) cells compared to that in
      normal human oral keratinocytes (NHOK). Moreover, abnormal DNA EJ activities were
      detected exclusively in HOK-16B and HNSCC cells due to microhomology-mediated and
      non-microhomology-mediated end-joining activities in these cells. These data
      indicated that aberrant DNA EJ activity may be partly responsible for genetic
      instability and oncogenic transformation.

PMID- 16596283
TI  - Apoptotic-inducing activity of novel polycyclic aromatic compounds in human
      leukemic cells.
AB  - Persistent but relatively limited research has been devoted to the use of
      compounds related to polycyclic aromatic hydrocarbons (PAH) as anticancer agents.
      In previous reports, we have described the cytotoxicity of a number of new and
      novel PAH against human cancer cell lines. However, the involved molecular
      mechanisms of inducing cell death were not elucidated. In the current study, we
      describe the apoptotic pathway as apparently playing a crucial role in induced
      cell death in human leukemia Jurkat T cells by several diamide and diamine PAH
      that contain chrysene as their core aromatic ring system. Structure-activity
      relationships were analyzed. Importantly, no effect was demonstrated in a normal,
      non-transformed line of human natural killer cells. These results provide
      additional evidence for the potential chemotherapeutic use of PAH.

PMID- 16596282
TI  - Adrenomedullin binding protein-1 is downregulated during polymicrobial sepsis in
      the rat.
AB  - We have previously shown that administration of adrenomedullin (AM) and AM
      binding protein-1 (AMBP-1) in combination maintains cardiovascular stability and
      reduces mortality in a rat model of sepsis. However, it is unknown whether AMBP-1
      is reduced under the septic condition and, if so, whether lipopolysaccharide
      (LPS) plays a role in down-regulating AMBP-1. To determine this, male adult
      Sprague-Dawley rats were subjected to either polymicrobial sepsis by cecal
      ligation and puncture (CLP), or endotoxemia by intraperitoneal injection of LPS
      (15 mg/kg body weight). In an additional group of animals, LPS neutralizing agent
      polymyxin B (PMB) was given intramuscularly at 0.5 h before and 9 h after CLP. At
      20 h after CLP (i.e. the late stage of sepsis) or endotoxemia, hepatic tissue and
      blood samples were collected. Hepatic AMBP-1 gene expression along with hepatic
      and plasma AMBP-1 protein levels were measured by RT-PCR and Western blot
      analysis, respectively. Our results showed that hepatic AMBP-1 gene expression
      decreased by 65%, hepatic AMBP-1 protein levels decreased by 72%, and plasma
      levels of AMBP-1 decreased by 59% at 20 h after CLP. Similar results were also
      seen in the animals receiving LPS injection. Administration of PMB, however,
      prevented the downregulation of AMBP-1 expression at 20 h after CLP. Thus, AMBP-1
      is downregulated in the late phase of sepsis, and LPS plays a critical role in
      the reduction of AMBP-1.

PMID- 16596284
TI  - Expression of pigment epithelial derived factor is reduced in non-small cell lung
      cancer and is linked to clinical outcome.
AB  - Angiogenesis is under the exquisite control of a network of angiogenic factors
      and anti-angiogenic factors. PEDF (pigment epithelial derived factor) is one of
      the known anti-angiogenesis factors and is naturally occurring in the body. There
      has been studies to show that the factor plays an important role in negating the
      angiogenic process in pathological conditions in the eye. However, little is
      known about its expression in solid tumors. The current study examined PEDF
      expression at protein and message levels and investigated its critical link with
      cancer progression and prognosis in patients with non-small cell lung cancer
      (NSCLC). We used immunohistochemistry to examine the protein expression of PEDF
      and to evaluate the microvessel density (MVD) in a cohort of 91 NSCLC patients.
      In addition, real-time quantitative PCR was used to measure levels of the PEDF
      transcript. PEDF was positively stained in cytoplasm of cancer cells, but at a
      lower level, compared with normal cells in the lung tissues. Low levels of PEDF
      were seen in 57.1% patients. The levels of PEDF appeared to be associated with
      MVD, in that patients with reduced PEDF had a significantly high MVD count
      (28.50), compared with patients with high levels of PEDF who had a 16.98 MVD
      count (p<0.0005). In univariate but not multivariate analysis PEDF was an
      independent prognostic factor. In real-time PCR analysis, PEDF mRNA level of
      cancer tissue was significantly lower than normal tissue (0.55+/-0.36 vs 0.72+/
      0.26, p=0.024, paired t-test). PEDF mRNA level in cancer tissue was negatively
      associated with TNM stage and the tumor size (p<0.05, independent t-test).
      Finally, low levels of PEDF in lung tumor tissues was associated with a
      significantly shorter survival (p=0.038) using Kaplan-Meier and Cox analyses. In
      this first study, PEDF was reduced at both protein and mRNA level in NSCLC tumors
      compared with normal lung tissues. This reduction is associated with an increase
      in microvessel density in tumors and significantly associated with TNM stage,
      tumor size and the overall survival. PEDF is an important factor in NSCLC
      development and may be a of prognostic value for NSCLC patients.

PMID- 16596285
TI  - Apoptotic activity of a novel synthetic cantharidin analogue on hepatoma cell
      lines.
AB  - Cantharidin isolated from Mylabris caraganae and other insects is used
      traditionally as an anti-cancer drug. However, its toxicity on the renal system
      and suppression effect on bone marrow limits its clinical usage. Recently, we
      have synthesized two cantharidin analogues, CAN 029 (compound 2) and CAN 030
      (compound 3). Although both showed an apoptotic induction ability on cancer
      cells, they were still relatively toxic towards non-malignant haematological
      disordered bone marrow. Based on the principle structure of cantharidin, we have
      further chemically synthesized another analogue, CAN 032. The cytotoxic activity
      of this analogue was screened on both Hep3B hepatocellular carcinoma and SK-Hep-1
      liver adenocarcinoma cell lines by [3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] (MTS) assay.
      Morphological changes of hepatoma cell lines were recorded under an inverted
      microscope. The possible tolerance of these analogues was further investigated
      using non-malignant haematological bone marrow primary culture. CAN 032 showed a
      significant cytotoxic response on both hepatoma cell lines in which the potencies
      were comparable to that of cantharidin. Further screening on the bone marrow
      tolerance revealed that compound CAN 032 showed a relatively less toxic effect.
      Phase contrast microscopy demonstrated that cell shrinkage, rounding, loss of
      adherent property and loss of colony-formation ability were induced. The dose
      dependence of the response of CAN 032 on Hep3B was further assayed by DNA
      fragmentation gel electrophoresis. The G1 peak of Hep3B cells was reduced.
      Chemically synthesized CAN 032 may provide an improved therapeutic advantage over
      traditional cantharidin.

PMID- 16596286
TI  - Comparative integromics on BMP/GDF family.
AB  - WNT, Notch, FGF, Hedgehog and BMP signaling pathways network together during
      embryogenesis, tissue regeneration, and carcinogenesis. BMP2, BMP3, BMP4, BMP5,
      BMP6, BMP7, BMP8A, BMP8B, BMP10, BMP15, AMH, GDF1, GDF2, GDF3, GDF5, GDF6, GDF7,
      GDF8, GDF9, GDF10, GDF11, and GDF15 are BMP/GDF family genes within the human
      genome; however, transcriptional regulation of BMP/GDF family members by the
      canonical WNT signaling pathway remains unclear. We searched for the TCF/LEF
      binding site within the promoter region of BMP/GDF family genes by using
      bioinformatics and human intelligence. Because four TCF/LEF-binding sites were
      identified within human GDF10 promoter, comparative genomics analyses on GDF10
      orthologs were further performed. Chimpanzee GDF10 gene, encoding a 477-amino
      acid protein, was identified within NW_112875.1 genome sequence. AY412135.1 was
      not the correct coding sequence for chimpanzee GDF10. Chimpanzee GDF10 showed
      99.2%, 83.2% and 47.4% total amino-acid identity with human GDF10, mouse Gdf10
      and human BMP3, respectively. RASGEF1A-GDF10-PRKG1 locus at human chromosome
      10q11 and BMP3-PRKG2-RASGEF1B locus at human chromosome 4q21 were paralogous
      regions with insertions/deletions and recombination. Human GDF10 mRNA was
      expressed in fetal cochlea, fetal lung, testis, retina, pineal gland, other
      neural tissues, head and neck tumors, while mouse Gdf10 mRNA was expressed in
      fetal liver, inner ear, cerebellum, other neural tissues, prostate and blood
      vessels. Four TCF/LEF-binding sites in human GDF10 promoter were conserved in
      chimpanzee GDF10 promoter, but not in the mouse Gdf10 promoter; however, another
      TCF/LEF-binding site occurred in mouse Gdf10 promoter. Four bHLH-binding sites in
      human GDF10 promoter were conserved in chimpanzee GDF10 promoter, but only one in
      mouse Gdf10 promoter. Primate GDF10 promoters were divergent from mouse Gdf10
      promoter. Because GDF10 was characterized as a potential target of canonical WNT
      signaling pathway in neural tissues, GDF10 is one of the targets of systems
      medicine, especially in the field of regenerative medicine.

PMID- 16596288
TI  - Review and meta-analysis of risk estimates for prostate cancer in pesticide
      manufacturing workers.
AB  - PURPOSE: The purpose of the present paper is to review cohort studies that
      examined the occurrence of prostate cancer in pesticide manufacturing workers in
      order to undertake a qualitative and quantitative evaluation of the risk as well
      as to assess the level of epidemiological evidence for each class of chemical
      compounds. METHODS: Following a systematic literature search, relative risk (RR)
      estimates for prostate cancer were extracted from 18 studies published between
      1984 and 2004. All studies were summarised and evaluated for homogeneity and
      publication bias. As no significant heterogeneity was detected, combined RR
      estimators were calculated using a fixed effect model. Meta-analyses were
      performed both on the whole set of data and for each chemical class separately.
      RESULTS: The meta-rate ratio estimate for all studies was 1.28 [95% confidence
      interval (CI) 1.05-1.58]. After stratification by specific chemical class,
      consistent increases in the risk of prostate cancer were found in all groups but
      statistical significance was found only for accidental or non-accidental exposure
      to phenoxy herbicides contaminated with dioxins and furans. There was no obvious
      indication of publication bias. CONCLUSION: The overall meta-analysis provides
      additional quantitative evidence consistent with prior reviews focusing on other
      groups exposed to pesticides (farmers, pesticide applicators). The results again
      point to occupational exposure to pesticides as a possible risk factor for
      prostate cancer but the question of causality remains unanswered. Epidemiological
      evidence did not allow identifying a specific pesticide or chemical class that
      would be responsible for the increased risk but the strongest evidence comes from
      workers exposed to phenoxy herbicides possibly in relation with dioxin and/or
      furan contamination.

PMID- 16596287
TI  - Ethanol extract from Artemisia vestita, a traditional Tibetan medicine, exerts
      anti-sepsis action through down-regulating the MAPK and NF-kappaB pathways.
AB  - Artemisia vestita Wall., a traditional Tibetan medicine, has wide clinical
      application for inflammatory diseases. However, its molecular mechanism of anti
      inflammatory effect is poorly understood. In the present study, we investigated
      the anti-inflammatory activity and underlying mechanism of the ethanol extract
      from Artemisia vestita (AV-ext) on lipopolysaccharide (LPS)-induced sepsis.
      Pretreatment with AV-ext significantly decreased the levels of tumor necrosis
      factor-alpha (TNF-alpha) in serum and liver and lung tissues, and improved the
      survival of mice with experimental sepsis. AV-ext also remarkably reduced the
      expression levels of TNF-alpha, interleukin-1beta and cyclooxygenase-2 in LPS
      stimulated RAW 264.7 macrophages and dose dependently suppressed the activation
      of mitogen-activated protein kinases (MAPKs), such as p38, extracellular signal
      regulated kinase (ERK1/2) and c-Jun NH2-terminal kinase (JNK). Furthermore,
      pretreatment with AV-ext dose dependently inhibited the activation of nuclear
      factor-kappaB (NF-kappaB), as well as the degradation and phosphorylation of
      inhibitory kappaB (IkappaB) in LPS-activated RAW 264.7 macrophages. These results
      collectively reveal that AV-ext inhibits TNF-alpha release from macrophages by
      suppressing MAPK and NF-kappaB signaling pathways and suggest that AV-ext may be
      beneficial for the treatment of endotoxin shock or sepsis.

PMID- 16596289
TI  - Of mice and women: light as a circadian stimulus in breast cancer research.
AB  - OBJECTIVE: Nocturnal rodents are frequently used as models in human breast cancer
      research, but these species have very different visual and circadian systems and,
      therefore, very different responses to optical radiation or, informally, light.
      Because of the impact of light on the circadian system and because recent
      evidence suggests that cancer risk might be related to circadian disruption, it
      is becoming increasingly clear that optical radiation must be properly
      characterized for both nocturnal rodents and diurnal humans to make significant
      progress in unraveling links between circadian disruption and breast cancer. In
      this paper, we propose a quantitative framework for comparing radiometric and
      photometric quantities in human and rodent studies. METHODS: We reviewed
      published research on light as a circadian stimulus for humans and rodents. Both
      suppression of nocturnal melatonin and phase shifting were examined as outcome
      measures for the circadian system. RESULTS: The data were used to develop
      quantitative comparisons regarding the absolute and spectral sensitivity for the
      circadian systems of humans and nocturnal rodents. CONCLUSIONS: Two models of
      circadian phototransduction, for mouse and humans, have been published providing
      spectral sensitivities for these two species. Despite some methodological
      variations among the studies reviewed, the circadian systems of nocturnal rodents
      are approximately 10,000 times more sensitive to optical radiation than that of
      humans. Circadian effectiveness of different sources for both humans and
      nocturnal rodents are offered together with a scale relating their absolute
      sensitivities. Instruments calibrated in terms of conventional photometric units
      (e.g., lux) will not accurately characterize the circadian stimulus for either
      humans or rodents.

PMID- 16596290
TI  - GSTM1 and GSTT1 polymorphisms, cigarette smoking, and risk of colon cancer: a
      population-based case-control study in North Carolina (United States).
AB  - Cigarette smoke is a risk factor for colon cancer, but the importance of dose and
      interaction with genetic susceptibility remain poorly understood. We used data
      from a population-based case control study, to examine the association between
      cigarette smoking and colon cancer in African Americans and whites, and colon
      cancer and polymorphisms in GSTM1 and GSTT1. A total of 554 cases of primary
      colon cancer and 874 controls were included in this analysis. We found no
      association between cigarette smoking (ever versus never) and colon cancer in
      African Americans (odds ratio (OR)=0.93, 95% confidence interval (CI)=0.65-1.33).
      In contrast, there was an increased risk of cigarette smoking in whites (OR=1.43,
      CI=1.05-1.94). There was a small increased risk of colon cancer for individuals
      with GSTM1 null (African Americans, OR=1.43, CI, 0.98-2.09; whites, OR=1.19, CI,
      0.90-1.58) and a decreased risk of colon cancer for individuals with GSTT1 null
      (African Americans, OR=0.59, CI: 0.40-0.86; whites, OR=0.72, CI: 0.53-1.00).
      There were weak interactions between GSTT1 null and cigarette smoking in whites,
      and GSTM1 null genotype and cigarette smoking in African Americans. GSTT1 and
      GSTM1 polymorphisms may be weakly related to colon cancer risk and there may be
      racial differences in gene-smoking interactions.

PMID- 16596292
TI  - Survival among patients with adenocarcinoma of the pancreas: a population-based
      study (United States).
AB  - OBJECTIVE: The purpose of the current study was to evaluate survival of patients
      diagnosed in California with adenocarcinoma of the pancreas by demographic and
      tumor-related factors. METHODS: Through the California Cancer Registry (CCR) we
      identified all California residents diagnosed with invasive pancreatic
      adenocarcinoma between 1994 and 2000. Demographic, tumor and treatment
      information was extracted from the CCR, and socioeconomic status (SES) was
      assigned based on census block group of residence. RESULTS: A total of 10,612
      eligible patients were identified of whom 1674 (15.8%) underwent surgical
      resection. Patients of lower SES were less likely to undergo resection and
      somewhat less likely to survive. Median survival was 3.5 months for patients who
      were not resected and 13.3 months for those who underwent resection. Adjuvant
      therapy was associated with a decreased risk of death among patients who
      underwent resection. CONCLUSIONS: This study is the largest population-based
      study to date to explore survival from pancreatic cancer among all age groups in
      a racially diverse population. Median survival was shorter than that reported
      from other series. Race/ethnicity did not have a significant effect on survival.
      However patients residing in poor neighborhoods were less likely to undergo
      resection and somewhat less likely to survive this disease.

PMID- 16596291
TI  - Perinatal exposures and breast cancer risk in the Western New York Exposures and
      Breast Cancer (WEB) Study.
AB  - BACKGROUND: There is increasing evidence that early life exposures, such as birth
      weight, infant feeding practices, birth rank and maternal age at delivery may
      play a role in breast carcinogenesis. METHODS: We conducted a case-control study
      of women aged 35-80 in Western New York (Western New York Exposure and Breast
      Cancer Study, the WEB Study, 1996-2001). The study included 845 women diagnosed
      with primary, incident, histologically confirmed breast cancer, and 1538 controls
      frequency-matched to cases on age, race, and county of residence. We conducted
      extensive in-person interviews including self-reported birth weight, history of
      having been breastfed, birth rank, and maternal age at delivery. RESULTS: Birth
      weight was significantly associated with pre- but not post-menopausal breast
      cancer risk. Compared to women whose birth weight was 5.5-7 pounds, we found an
      increased risk associated with a birth weight greater than 8.5 pounds (OR 1.84,
      95%CI: 1.12-3.02). Risk was also increased for pre- but not post-menopausal women
      who had not been breastfed (OR 1.78, 95%CI: 1.21-2.60). Birth order and maternal
      age at delivery were not significantly associated with breast cancer risk.
      CONCLUSIONS: Our findings are consistent with other studies showing breast cancer
      risk associated with birth weight for pre- but not post-menopausal breast cancer.
      As we found in an earlier study, having been breastfed was associated with
      decreased risk. These findings add to the accumulating evidence that early life
      events impact women's subsequent breast cancer risk.

PMID- 16596293
TI  - Incidences and trends of second cancers in female breast cancer patients: a fixed
      inception cohort-based analysis (United States).
AB  - OBJECTIVE: To determine incidences and time trends of second cancers among female
      breast cancer patients. METHODS: Using data of the National Cancer Institute's
      Surveillance, Epidemiology, and End Results (SEER) Program, we designed three
      inception cohorts: 1975-1977 (n=25,920), 1983-1985 (n=32,722) and 1991-1993
      (n=40,819), and analyzed their incidences of second cancers during the first 8
      years after initial breast cancer diagnosis. RESULTS: Between the 1970s and the
      1990s, the incidence rate of malignant second cancer significantly increased
      among female breast cancer patients, of which second non-Hodgkin's lymphoma and
      kidney cancer increased by about 150%, while second cancers of the thyroid,
      uterine corpus and skin melanoma increased 80%, and cancer of the lung increased
      50%. The patterns of trend of second cancers were somewhat similar to those of
      the general population except for second endometrial cancer at all ages and
      second leukemia and skin melanoma among young patients aged 20-49. In the 1990s,
      the risk ratios (RR) of all sites cancer were found to be 5.5 (95% CI=5.0-6.1)
      for age 20-49, 1.3 (1.3-1.4) for age 50-64, and 1.2 (1.1-1.2) for age 65 and
      over, comparing breast cancer patients to general population. Additionally,
      radiotherapy slightly increased the risks of second leukemia (RR=1.8, 1.2-2.8),
      and second endometrial (RR=1.3, 1.0-1.6) and breast (RR=1.2, 1.1-1.3) cancers.
      CONCLUSIONS: The fixed inception cohort method is valid for analyzing cancer
      registry-based second cancer data. By this method, we found that the incidence of
      second cancer has substantially increased among female breast cancer patients
      over the past 25 years. Observed changes in incidence may partially reflect the
      effect of treatments. Because the absolute number of affected patients is small,
      however, the breast cancer treatments have remained safe for most patients.

PMID- 16596294
TI  - Age-specific fluoride exposure in drinking water and osteosarcoma (United
      States).
AB  - OBJECTIVE: We explored age-specific and gender-specific effects of fluoride level
      in drinking water and the incidence of osteosarcoma. METHODS: We used data from a
      matched case-control study conducted through 11 hospitals in the United States
      that included a complete residential history for each patient and type of
      drinking water (public, private well, bottled) used at each address. Our analysis
      was limited to cases less than 20 years old. We standardized fluoride exposure
      estimates based on CDC-recommended target levels that take climate into account.
      We categorized exposure into three groups (<30%, 30-99%, >99% of target) and used
      conditional logistic regression to estimate odds ratios. RESULTS: Analysis is
      based on 103 cases under the age of 20 and 215 matched controls. For males, the
      unadjusted odds ratios for higher exposures were greater than 1.0 at each
      exposure age, reaching a peak of 4.07 (95% CI 1.43, 11.56) at age 7 years for the
      highest exposure. Adjusting for potential confounders produced similar results
      with an adjusted odds ratio for males of 5.46 (95% CI 1.50, 19.90) at age 7
      years. This association was not apparent among females. CONCLUSIONS: Our
      exploratory analysis found an association between fluoride exposure in drinking
      water during childhood and the incidence of osteosarcoma among males but not
      consistently among females. Further research is required to confirm or refute
      this observation.

PMID- 16596295
TI  - Milk, dairy products and cancer risk (Italy).
AB  - BACKGROUND: Inconclusive information is available on the potential role of milk
      and dairy products on the risk of cancer at several sites. METHODS: We analyzed
      data from a large and integrated network of hospital-based case-control studies
      in Italy on cancers of the oral cavity and pharynx (598 cases, 1491 controls),
      oesophagus (304 cases, 743 controls), colorectum (1953 cases, 4154 controls),
      larynx (460 cases, 1088 controls), breast (2569 cases, 2588 controls), ovary
      (1031 cases, 2411 controls) and prostate (1294 cases, 1451 controls). RESULTS:
      Multivariate odds ratio (OR) for the highest consumption level of any type of
      milk was 0.94 (95% confidence interval, CI: 0.61-1.33) for cancers of the oral
      cavity and pharynx, 1.20 (95% CI: 0.76-1.90) for oesophageal, 0.77 (95% CI: 0.62
      0.96) for colon, 0.80 (95% CI: 0.60-1.05) for rectal, 0.83 (95% CI: 0.56-1.21)
      for laryngeal, 0.91 (95% CI: 0.76-1.10) for breast, 0.89 (95% CI: 0.68-1.15) for
      ovarian and 1.08 (95% CI: 0.84-1.37) for prostate cancer. A significant trend in
      risk was found for colon cancer only. Inverse associations were observed between
      consumption of skim milk and cancers of colon (OR=0.84; 95% CI: 0.73-0.97),
      rectum (OR=0.76; 95% CI: 0.64-0.91), breast (OR=0.87; 95% CI: 0.77-0.98) and
      ovary (OR=0.77; 95% CI: 0.66-0.91). Conversely, whole milk consumption was
      directly associated with cancer of the rectum (OR=1.22; 95% CI: 1.03-1.44) and
      ovary (OR=1.25; 95% CI: 1.07-1.46). High consumption of cheese was inversely
      related to colon cancer risk (OR=0.80; 95% CI: 0.67-0.95). CONCLUSIONS: There was
      a modest direct association between milk and dairy products and prostate cancer,
      and a moderate inverse one for colorectal cancer. However, our findings indicate
      that milk and dairy products are not strong risk indicators for any of the
      cancers considered.

PMID- 16596296
TI  - Impact of women's experiences during mammography on adherence to rescreening
      (United States).
AB  - OBJECTIVE: To examine the relationship between womens' experiences during
      mammography and their likelihood of being rescreened after receiving a negative
      or benign mammogram. METHODS: Telephone interview and medical record data were
      collected from a random sample of enrollees from four states in a national
      screening program targeting uninsured and underinsured women at least 30 months
      after they had undergone an index mammogram in 1997. We calculated 30-month
      rescreening rates by prior mammography characteristics including pain and
      embarrassment, worry, convenience of appointment time, treatment by staff, and
      financial considerations. RESULTS: Of the 2,000 women in the sampling frame,
      1,895 (93.6%) were located, 1,685 (88.6%) were interviewed and 1,680 provided
      data required for our analysis. Overall, 81.5% of the women had undergone
      rescreening. More than 90% of the women reported being 'satisfied' or 'very
      satisfied' with treatment by facility staff, facility location and wait time
      during the appointment. Statistically significant decreased rescreening rates
      were seen for women who reported feeling embarrassed and for women reporting
      dissatisfaction with ability to schedule a convenient appointment time.
      CONCLUSION: These results suggest that providing additional reassurance and
      privacy may increase rescreening rates.

PMID- 16596297
TI  - Use of the spatial scan statistic to identify geographic variations in late stage
      colorectal cancer in California (United States).
AB  - OBJECTIVES: To identify geographic variations in colorectal cancer by stage at
      diagnosis in California using a descriptive analysis coupled with a spatial
      analysis and to discuss methodological considerations concerning the spatial
      statistical method. METHODS: We analyzed 59,076 colorectal cancer cases diagnosed
      in California from 1996 to 2000 by logistic regression and by a spatial scan
      statistic to identify areas with a higher and lower relative risk of late-stage
      colorectal cancer. RESULTS: In California, 57% of overall cases of colorectal
      cancer were diagnosed at a late stage. Californians diagnosed with late-stage
      colorectal cancer were more likely to be Hispanic and living in areas of lower
      socioeconomic status. The spatial scan identified two areas where the observed
      number of late-stage cancer was different than the number expected from the
      distribution in the rest of the state. CONCLUSIONS: Spatial scan analyses can
      complement descriptive statistics, but results must be interpreted with
      consideration of factors that affect the ability to detect meaningful differences
      such as the number of events observed, accuracy in geocoding rural versus urban
      addresses, and the difficulty of adjusting for covariates.

PMID- 16596298
TI  - Relation of anthropometric measurements to ovarian cancer risk in a population
      based case-control study (United States).
AB  - OBJECTIVE: To examine the relationship between anthropometric measures and
      ovarian cancer by menopausal status. METHODS: We analyzed data from a population
      based case-control study comprised of 700 incident cases of epithelial ovarian
      cancer and 5,943 population controls from Massachusetts and Wisconsin enrolled
      between 1993 and 2001. In a telephone interview, information was gathered on
      established ovarian cancer risk factors, as well as adult height and age-specific
      body weight. Logistic regression was used to estimate multivariate-adjusted odds
      ratios (ORs) and 95% confidence intervals (CIs) for body mass index (BMI)
      throughout life. RESULTS: Recent BMI had no significant association with ovarian
      cancer risk (P-trend 0.14 for continuous BMI), after adjustment for age and other
      ovarian cancer risk factors. However, a non-significant positive association
      (overall P-trend 0.08) was observed for BMI at age 20; the risk estimate
      comparing a body mass of >25 kg/m2 to the lowest quintile (<or=18.88 kg/m2) was
      moderately but non-significantly elevated (OR 1.46; 95% CI 0.92, 2.31).
      CONCLUSION: Results of this study suggest that maintenance of a lean body mass,
      particularly in early adult life, may decrease ovarian cancer risk.

PMID- 16596299
TI  - Consumption of alcoholic beverages and risk of lung cancer: results from two case
      control studies in Montreal, Canada.
AB  - OBJECTIVE: To investigate the association between consumption of alcoholic
      beverages and lung cancer risk. METHODS: Data were collected in two population
      based case-control studies, conducted in Montreal (Study I--mid-1980s and Study
      II--mid-1990s). Study I included 699 cases and 507 controls, all males; Study II
      included 1094 cases and 1468 controls, males and females. In each study group
      (Study I men, Study II men and Study II women) odds ratios (OR) were estimated
      for the associations between beer, wine or spirits consumption and lung cancer,
      while carefully adjusting for smoking and other covariates. The reference
      category included abstainers and occasional drinkers. RESULTS: For Study I men,
      lung cancer risk increased with the average number of beers/week consumed (for 1
      6 beers/week: OR=1.2, 95% confidence interval (CI): 0.9-1.7; for >or=7
      beers/week: OR=1.5, 95% CI: 1.1-2.1). For Study II men, beer consumption appeared
      harmful only among subjects with low fruit and vegetable consumption. In Study
      II, wine consumers had low lung cancer risk, particularly those reporting 1-6
      glasses/week (women: OR=0.3, 95% CI: 0.2-0.4; men: OR=0.6, 95% CI: 0.4-0.8).
      CONCLUSIONS: Beer consumption increased lung cancer risk, particularly so among
      men who had relatively low fruit and vegetable consumption. Moderate wine
      drinkers had decreased lung cancer risk.

PMID- 16596300
TI  - Caution needed in fluoride and osteosarcoma study.

PMID- 16596301
TI  - Cancer and rhythm.

PMID- 16596302
TI  - Biological clocks and shift work: circadian dysregulation and potential long-term
      effects.
AB  - Long-term epidemiologic studies on large numbers of night and rotating shift
      workers have suggested an increase in the incidence of breast and colon cancer in
      these populations. These studies suffer from poor definition and quantification
      of the work schedules of the exposed subjects. Against this background, the
      pathophysiology of phase shift and phase adaptation is reviewed. A phase shift as
      experienced in night and rotating shift work involves desynchronization at the
      molecular level in the circadian oscillators in the central nervous tissue and in
      most peripheral tissues of the body. There is a change in the coordination
      between oscillators with transient loss of control by the master-oscillator (the
      Suprachiasmatic Nucleus, SCN) in the hypothalamus. The implications of the
      pathophysiology of phase shift are discussed for long-term health effects and for
      the design of ergonomic work schedules minimizing the adverse health effects upon
      the worker.

PMID- 16596303
TI  - Artificial lighting in the industrialized world: circadian disruption and breast
      cancer.
AB  - Breast cancer risk is high in industrialized societies, and increases as
      developing countries become more Westernized. The reasons are poorly understood.
      One possibility is circadian disruption from aspects of modern life, in
      particular the increasing use of electric power to light the night, and provide a
      sun-free environment during the day inside buildings. Circadian disruption could
      lead to alterations in melatonin production and in changing the molecular time of
      the circadian clock in the suprachiasmatic nuclei (SCN). There is evidence in
      humans that the endogenous melatonin rhythm is stronger for persons in a bright
      day environment than in a dim-day environment; and the light intensity necessary
      to suppress melatonin at night continues to decline as new experiments are done.
      Melatonin suppression can increase breast tumorigenesis in experimental animals,
      and altering the endogenous clock mechanism may have downstream effects on cell
      cycle regulatory genes pertinent to breast tissue development and susceptibility.
      Therefore, maintenance of a solar day-aligned circadian rhythm in endogenous
      melatonin and in clock gene expression by exposure to a bright day and a dark
      night, may be a worthy goal. However, exogenous administration of melatonin in an
      attempt to achieve this goal may have an untoward effect given that pharmacologic
      dosing with melatonin has been shown to phase shift humans depending on the time
      of day it's given. Exogenous melatonin may therefore contribute to circadian
      disruption rather than alleviate it.

PMID- 16596304
TI  - Disruption of circadian coordination and malignant growth.
AB  - Altered circadian rhythms predicted for poor survival in patients with metastatic
      colorectal or breast cancer. An increased incidence of cancers has been reported
      in flying attendants and in women working predominantly at night. To explore the
      contribution of circadian structure to tumor growth we ablated the 24-h rest
      activity cycle and markedly altered the rhythms in body temperature, serum
      corticosterone and lymphocyte count in mice by complete stereotaxic destruction
      of the suprachiasmatic nuclei (SCN) or by subjecting the mice to experimental
      chronic jet-lag. Such disruption of circadian coordination significantly
      accelerated malignant growth in two transplantable tumor models, Glasgow
      osteosarcoma and Pancreatic adenocarcinoma. The mRNA expression of clock genes
      per2 and reverb-alpha in controls displayed significant circadian rhythms in the
      liver (Cosinor, p=0.006 and p=0.003, respectively) and in the tumor (p=0.04 and
      p<0.001, respectively). Both rhythms were suppressed in the liver and in the
      tumor of jet lagged mice. This functional disturbance of molecular clock resulted
      in down regulation of p53 and overexpression of c-Myc, two effects which may
      favor cancer growth. CONCLUSIONS: These results indicate that circadian system
      could play an important role in malignant growth control. This should be taken
      into consideration in cancer prevention and therapy.

PMID- 16596305
TI  - Light during darkness and cancer: relationships in circadian photoreception and
      tumor biology.
AB  - The relationship between circadian phototransduction and circadian-regulated
      processes is poorly understood. Melatonin, commonly a circadian phase marker, may
      play a direct role in a myriad of physiologic processes. The circadian rhythm for
      pineal melatonin secretion is regulated by the hypothalamic suprachiasmatic
      nucleus (SCN). Its neural source of light input is a unique subset of
      intrinsically photosensitive retinal ganglion cells expressing melanopsin, the
      primary circadian photopigment in rodents and primates. Action spectra of
      melatonin suppression by light have shown that light in the 446-477 nm range,
      distinct from the visual system's peak sensitivity, is optimal for stimulating
      the human circadian system. Breast cancer is the oncological disease entity whose
      relationship to circadian rhythm fluctuations has perhaps been most extensively
      studied. Empirical data has increasingly supported the hypothesis that higher
      risk of breast cancer in industrialized countries is partly due to increased
      exposure to light at night. Studies of tumor biology implicate melatonin as a
      potential mediator of this effect. Yet, causality between lifestyle factors and
      circadian tumor biology remains elusive and likely reflects significant
      variability with physiologic context. Continued rigorous empirical inquiry into
      the physiology and clinical implications of these habitual, integrated aspects of
      life is highly warranted at this time.

PMID- 16596306
TI  - Tumor suppression by the mammalian Period genes.
AB  - The Period (Per) genes are key circadian rhythm regulators in mammals. Expression
      of the mouse Per (mPer) genes have diurnal pattern in the suprachiamstic nuclei
      and in peripheral tissues. Genetic ablation mPER1 and mPER2 function results in a
      complete loss of circadian rhythm control based on wheel running activity in
      mice. In addition, these animals also display apparent premature aging and
      significant increase in neoplastic and hyperplastic phenotypes. When challenged
      by gamma-radiation, mPer2 deficient mice response by rapid hair graying, are
      deficient in p53-mediated apoptosis in thymocytes and have robust tumor
      occurrences. Our studies have demonstrated that the circadian clock function is
      very important for cell cycle, DNA damage response and tumor suppression in vivo.
      Temporal expression of genes involved in cell cycle regulation and tumor
      suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha is
      deregulated in mPer2 mutant mice. In addition, genetic studies have demonstrated
      that many key regulators of cell cycle and growth control are also important
      circadian clock regulators confirming the critical role of circadian function in
      organismal homeostasis. Recently studies of human breast and endometrial cancers
      revealed that the loss and deregulation of PERIOD proteins is common in the tumor
      cells.

PMID- 16596307
TI  - Risk of breast cancer after night- and shift work: current evidence and ongoing
      studies in Denmark.
AB  - Breast cancer is the most frequent cancer among women, and the number is
      increasing worldwide. This tumour is strongly associated with Western lifestyle,
      but the specific risk factors behind this observation are not well known.
      Exposure to light-at-night, including disturbance of the circadian rhythm,
      possibly mediated via the melatonin synthesis and clock genes, has been suggested
      as a contributing cause of breast cancer. Since shift- and night-time work is
      prevalent and increasing in modern societies, this exposure may be of public
      health concern, and contribute to the continuing elevation in breast cancer risk.
      Until now only few epidemiological studies have evaluated breast cancer risk
      after shift and night work. Although these studies are all suffering from
      methodological problems, especially concerning assessment of light exposure,
      results have consistently shown an increase in risk associated with night and
      shift work. Good opportunities for epidemiological cancer research exist in
      Denmark, and several studies on different aspects of breast cancer, work
      schedules, light exposure and melatonin levels are ongoing in order to further
      examine different aspects of this issue.

PMID- 16596308
TI  - Circadian disruption, shift work and the risk of cancer: a summary of the
      evidence and studies in Seattle.
AB  - There is increasing interest in the possibility that disruption of normal
      circadian rhythm may increase the risk of developing cancer. Persons who engage
      in nightshift work may exhibit altered nighttime melatonin levels and
      reproductive hormone profiles that could increase the risk of hormone-related
      diseases, including breast cancer. Epidemiologic studies are now beginning to
      emerge suggesting that women who work at night, and who experience sleep
      deprivation, circadian disruption, and exposure to light-at-night are at an
      increased risk of breast cancer, and possibly colorectal cancer as well. Several
      studies have been conducted in Seattle recently to investigate the effects of
      factors that can disrupt circadian rhythm and alter normal nocturnal production
      of melatonin and reproductive hormones of relevance to breast cancer etiology.
      Studies completed to date have found: (1) an increased risk of breast cancer
      associated with indicators of exposure to light-at-night and night shift work;
      and (2) decreased nocturnal urinary levels of 6-sulphatoxymelatonin associated
      with exposure to 60-Hz magnetic fields in the bedroom the same night, and a
      number of other factors including hours of daylight, season, alcohol consumption
      and body mass index. Recently completed is an experimental crossover study
      designed to investigate whether exposure to a 60-Hz magnetic field under
      controlled conditions in the home sleeping environment is associated with a
      decrease in nocturnal urinary concentration of 6-sulphatoxymelatonin, and an
      increase in the urinary concentration of luteinizing hormone, follicle
      stimulating hormone, and estradiol in a sample of healthy women of reproductive
      age. Presently underway is a study to determine whether working at night is
      associated with decreased levels of urinary 6-sulphatoxymelatonin, and increased
      urinary concentrations of the reproductive hormones listed above in a sample of
      healthy women of reproductive age, and to elucidate characteristics of sleep
      among night shift workers that are related to the hormone patterns identified. A
      proposal is under review to extend these studies to a sample of healthy men to
      investigate whether working at night is associated with decreased levels of
      urinary 6-sulphatoxymelatonin, and increased concentrations of urinary cortisol
      and cortisone, urinary levels of a number of androgen metabolites, and serum
      concentrations of a number of reproductive hormones. Secondarily, the proposed
      study will elucidate characteristics of sleep among night shift workers that are
      related to the hormone patterns identified, as well as investigate whether
      polymorphisms of the genes thought to regulate the human circadian clock are
      associated with the ability to adapt to night shift work. It is anticipated that
      collectively these studies will enhance our understanding of the role of
      circadian disruption in the etiology of cancer.

PMID- 16596309
TI  - Is melatonin the hormonal missing link between magnetic field effects and human
      diseases?
AB  - The disruption of melatonin secretion has been largely studied since it could
      provide the missing link between the exposure to 50/60-Hz electric and magnetic
      fields (EMF) and the occurrence of possible health effects as the "melatonin
      hypothesis". We analysed the current experimental data from animal (rodents)
      where contradictory results have been observed, and from human studies conducted
      with volunteers or with workers in various conditions of exposure, biological
      endpoints and metrics. In humans, even in long lasting exposures, the overall
      results of these studies do not support the "melatonin hypothesis". It is
      unlikely that malignancies or mood disorders reported by people exposed to 50/60
      Hz EMF could be related to the disruption of the melatonin levels.

PMID- 16596310
TI  - Electromagnetic fields and female breast cancer.
AB  - The possibility that long term exposure to relatively weak power frequency
      electromagnetic fields (EMF) could increase the risk of breast cancer has been
      investigated during the past decade. The hypothesis is based on the assumption
      that magnetic field exposures suppress melatonin production and that melatonin is
      protective against breast cancer. Most epidemiological studies have indicated
      little or no overall effect of EMF exposure, but some early studies suggested
      effects among premenopausal women, particularly for estrogen receptor positive
      breast tumors. The early studies were often limited by small numbers, crude
      exposure information and lack of information on confounding factors. In more
      recent occupational studies, again no overall risk increases were reported, but
      some studies found increased risks in certain subgroups, although with no
      consistent pattern across studies. A recent very large occupational study with
      improved exposure assessment and enough statistical power also for subgroup
      analyses found no indications of increased risks in any subgroups. Most of the
      recent well-designed residential studies report no increased risks, and similar
      findings are reported in the majority of studies of bed heating devices. Overall,
      the weight of the evidence available today does not suggest an increased risk of
      breast cancer related to EMF exposure.

PMID- 16596312
TI  - Does incidence of breast cancer and prostate cancer decrease with increasing
      degree of visual impairment.
AB  - OBJECTIVE: The issue of light at night and cancer continuously attracts
      discussion. The major hypotheses are that melatonin may decrease risk of hormone
      related cancers, particularly breast cancer, or even act as a potent antioxidant
      and thus have a protective effect against cancer development in general. METHODS:
      We tested the hypothesis that blind persons are at lower risk of cancer in a
      follow-up study linking a cohort of 17,557 persons with visual impairment
      identified from the Finnish Register of Visual Impairment with cancer incidence
      data of the Finnish Cancer Registry for years 1983-2003. RESULTS: Breast cancer
      risk in females decreased by degree of visual impairment, and a similar but less
      consistent trend was observed for prostate cancer in males. The incidence for the
      remaining cancers among nearly to totally blind persons was significantly higher
      than in average Finnish population. CONCLUSIONS: Our findings add to the
      suggestive epidemiological evidence for a decreased risk of hormone-related
      cancers in people with visual impairment and, consequently, a relationship
      between visible light at night and breast cancer risk. The result is strongly
      against the hypothesis of a systemic protective effect related lack of visible
      light.

PMID- 16596311
TI  - The anti-tumor activity of pineal melatonin and cancer enhancing life styles in
      industrialized societies.
AB  - This review discusses the potential role of the anti-tumor activity of pineal
      melatonin for the aetiology and prevention of cancers related to life-styles in
      industrialized societies, e.g. frequent long-distance flights as well as chronic
      night shift work leading to circadian disturbances of neuroendocrine parameters
      including melatonin. Experimental studies show that melatonin controls not only
      the growth of well-differentiated cancers, but also possesses anti-carcinogenic
      properties. Therefore, it is plausible that disturbances of circadian melatonin
      rhythmicity could be functionally involved in elevated cancer risks among aircrew
      members and nurses frequently working on night shifts. Due to the suppression of
      melatonin by light it can be assumed that too much artificial light at night
      could, at least in part, be responsible for generally increasing rates of e.g.
      breast cancer in industrialized countries. It is discussed under which conditions
      a transient substitutional therapy with melatonin could be justified or which
      forms of living could help to physiologically foster melatonin secretion to
      optimise control over cancerous growth and development.

PMID- 16596313
TI  - Circulating melatonin levels: possible link between Parkinson's disease and
      cancer risk?
AB  - Lower rates of cancer mortality/incidence in patients with Parkinson's disease
      (PD) have given rise to speculations about risk or preventative factors common to
      both diseases, including life-style factors (such as smoking) and genetic
      susceptibility. Melatonin, a hormone known for its sleep regulatory effects, may
      play an important role in carcinogenesis as suggested by substantial laboratory
      and less direct epidemiologic evidence. Particularly, a reduction in melatonin,
      such as experienced by persons who are exposed to light at night, appears to
      increase cancer risk. Variations in melatonin levels have been linked to PD in
      several different ways. Some studies show higher morning melatonin levels in PD
      patients than in healthy controls. One could speculate that the sleep disorders
      that affect almost two thirds of those suffering from PD and can precede PD motor
      symptoms by several years may be associated with variations in melatonin levels.
      Moreover, in animal models, interventions that increase the bioavailability of
      melatonin appears to increase the severity of parkinsonian symptoms, whereas
      reduction in melatonin by pinealectomy or exposure to bright light can enhance
      recovery from parkinsonisms symptoms. Finally, preliminary epidemiological
      evidence suggests that longer years of working night shifts is associated with a
      reduced risk of PD among participants of the Nurses' Health Study (NHS), whereas
      longer hours of sleep appear to increase their risk. In sum, while lower
      melatonin concentrations may predict a higher cancer risk, there is also some
      evidence that they may be associated with a lower risk of PD. We therefore
      hypothesize that elevated circulating melatonin levels in PD patients may
      contribute to their lower cancer rates.

PMID- 16596314
TI  - Melatonin treatment in obese patients with childhood craniopharyngioma and
      increased daytime sleepiness.
AB  - Craniopharyngioma is a rare dysontogenetic benign tumor. Patients frequently
      suffer from endocrine deficiencies, sleep disturbances and obesity due to
      pituitary and hypothalamic lesions. A self-assessment daytime sleepiness
      questionnaire (German version of the Epworth Sleepiness Scale [ESS]) was used to
      evaluate 79 patients with childhood craniopharyngioma. Because hypothalamic
      lesions may explain daytime sleepiness in craniopharyngioma patients, salivary
      melatonin and cortisol concentrations were examined in severely obese
      (BMI>or=4SD) and non severely obese (BMI<4SD) craniopharyngioma patients (n=79),
      patients with hypothalamic pilocytic astrocytoma (n=19), and control subjects
      (n=30). Using a general linear model procedure analyzing the influence of BMI and
      tumor diagnosis on diurnal salivary melatonin we found that morning salivary
      melatonin levels were related to BMI (F test: p-value=0.004) and tumor diagnosis
      (F-test: p-value=0.032). Also for nighttime salivary melatonin levels significant
      relations with BMI (p-value in F-test: <0.001) and tumor diagnosis (p-value in F
      test: 0.025) were detectable. Melatonin concentrations in saliva of
      craniopharyngioma patients collected at nighttime or in the morning showed a
      negative correlation (Spearman's rho: -0.42; p=0.001; Spearman's rho: -0.31;
      p=0.020) with the patient's ESS score. Severely obese craniopharyngioma patients
      and severely obese hypothalamic tumor patients had similar patterns of melatonin
      secretion. Differences in terms of diurnal salivary cortisol concentrations were
      not detectable when patient groups and controls were compared. As decreased
      nocturnal melatonin levels were associated with increased daytime sleepiness, BMI
      and hypothalamic tumor diagnosis, we initiated an experimental melatonin
      substitution in 10 adult obese patients (5f/5m) with childhood craniopharyngioma.
      In all 10 patients with childhood craniopharyngioma the degree of daytime
      sleepiness significantly improved based on activity diaries, ESS, self assessment
      questionnaires and actimetry. We speculate that hypothalamic lesions might be
      responsible for both obesity and daytime sleepiness. As first experiences with
      experimental melatonin substitution were promising, further randomized double
      blinded studies on the beneficial effects of melatonin substitution on daytime
      sleepiness and weight control in these patients are warranted.

PMID- 16596315
TI  - Why life oscillates--from a topographical towards a functional chronobiology.
AB  - Chronobiology has identified a multitude of rhythms within our body as well as
      within each living cell. Some of these rhythms, such as the circadian and
      circannual, interact with our environment, while others run on their own, but are
      often coupled to the circadian or to other body rhythms. Recent evidence shows
      that these rhythms might be more important for our health than expected:
      Disturbance of the circadian rhythms by jet lag or shift work not only evokes
      autonomic disturbances but also increases the incidence of cancer, as shown in
      this issue of Cancer Causes and Control. The occurrence of rhythms in the
      organism obviously bears several advantages: (1) It increases organismic
      stability by calibrating the system's characteristics: Regulation curves in time
      and space are crucial for controlling physiological long-term stability. To
      determine its properties continuously the system varies its parameters slightly
      over several time scales at different frequencies-akin to what our body does,
      e.g. in heart-rate variability. (2) Tuning and synchronization of rhythms saves
      energy: It was Huygens who observed that clocks on a wall tend to synchronize
      their beats. It turned out later that synchronisation is a very common phenomenon
      observed in bodies' rhythms and can be found, for example, when we relax or
      sleep. At such times energy consumption is minimal, our body working most
      efficiently. (3) Temporal compartmentalization allows polar events to occur in
      the same space unit: there are polarities in the universe of our body, which
      cannot happen simultaneously. Systole and diastole, inspiration and expiration,
      work and relaxation, wakefulness and sleep, reductive and oxidative states cannot
      be performed efficiently at the same time and place. Temporal
      compartmentalization is probably the most efficient way to mediate between these
      polarities. Chronobiology and chronomedicine are opening a new and very exciting
      understanding of our bodies' regulation. The biological time and its oscillations
      gain more attention and importance as these interrelations are understood.

PMID- 16596316
TI  - The use of chronobiotics in the resynchronization of the sleep-wake cycle.
AB  - Treatment of circadian rhythm disorders, whether precipitated by intrinsic
      factors (e.g., sleep disorders, blindness, mental disorders, aging) or by
      extrinsic factors (e.g., shift work, jet-lag) has led to the development of a new
      type of agents called 'chronobiotics', among which melatonin is the prototype.
      The term 'chronobiotic' defines as a substance capable of shifting the phase of
      the circadian time system thus re-entraining circadian rhythms. Melatonin
      administration synchronizes the sleep-wake cycle in blind people and in
      individuals suffering from delayed sleep phase syndrome or jet lag, as well in
      shift-workers. The effect of melatonin on sleep is probably the consequence of
      increasing sleep propensity (by inducing a fall in body temperature) and of a
      synchronizing effect on the circadian clock (chronobiotic effect). We
      successfully employed the timely use of three factors (melatonin treatment,
      exposure to light, physical exercise) to hasten the resynchronization after
      transmeridian flights comprising 12-13 time zones, from an average of 8-10 days
      to about 2 days. Daily melatonin production decreases with age, and in several
      pathologies, attaining its lowest values in Alzheimer's dementia patients. About
      45% of dementia patients have severe disruptions in their sleep-wakefulness
      cycle. Both in aged subjects having very minimal sleep disorders as well as in
      demented patients with a very severe disorganization of the sleep-wake cycle,
      melatonin treatment reduced the variability of sleep onset and restored sleep.

PMID- 16596317
TI  - Chronotherapeutics: the relevance of timing in cancer therapy.
AB  - BACKGROUND: Cell physiology is regulated along the 24-h time scale by a circadian
      timing system composed of molecular clocks within each cell and a central
      coordination system in the brain. The mammalian molecular clock is made of
      interconnected molecular loops involving at least 12 circadian genes. The
      cellular clocks are coordinated by the suprachiasmatic nuclei, a hypothalamic
      pacemaker which also helps the organism adjust to environmental cycles. The rest
      activity rhythm is a reliable marker of the circadian system function in both
      rodents and man. This circadian organization is responsible for predictable
      changes in the tolerability and efficacy of anticancer agents, and possibly also
      in tumor promotion or growth. METHODS: Expected least toxic times of chemotherapy
      were extrapolated from experimental models to human subjects with reference to
      the rest-activity cycle. The clinical relevance of the chronotherapy principle,
      i.e. treatment administration as a function of rhythms, has been demonstrated in
      randomized multicenter trials. RESULTS: Chronotherapeutic schedules have been
      used to safely document the activity of the association of oxaliplatin, 5-FU and
      leucovorin against metastatic colorectal cancer and to set up a new
      medicosurgical management of this disease which achieved unprecedented long term
      survival. CONCLUSION: The chronotherapy concept offers further promises for
      improving current cancer treatment options as well as for optimizing the
      development of new anticancer or supportive agents.

PMID- 16596318
TI  - Force enhancement at different levels of voluntary contraction in human adductor
      pollicis.
AB  - There is substantial evidence that the steady-state isometric force following
      active muscle stretch is greater than the corresponding isometric force for sub
      maximal and maximal electrically induced contractions, and for maximal voluntary
      contractions (MVC). This so-called force enhancement (FE) has not been
      investigated systematically for sub-MVC. Recently, we found that FE only occurred
      in about half of all tested subjects at 30% of MVC in the adductor pollicis
      muscle, suggesting that FE for voluntary contractions might depend on the level
      of activation. Therefore, the purpose of this study was to determine if FE during
      voluntary contractions is associated with activation. We hypothesized that FE
      increases with increasing levels of activation, and thus increasing levels of
      effort. Subjects (n=12) performed voluntary contractions of the adductor pollicis
      using a custom-built dynamometer at 10 and 60% of maximal effort. There was
      consistent FE in 4 of 12 subjects at 10% and in 10 of 12 subjects at 60% of
      maximal voluntary effort. Furthermore, the absolute FE increased from 10 to 60%
      of maximal voluntary effort. The results of this study, together with previous
      results on the same subject group at 30% and other subjects at 100% of maximal
      voluntary effort, suggest that FE systematically increases with increasing levels
      of voluntary contraction. The mechanisms responsible for this increased FE remain
      unclear.

PMID- 16596321
TI  - Subclavian artery pseudoaneurysm in Behcet's disease.
AB  - Behcet's disease (BD) is an autoimmune, multisystemic, and chronic inflammatory
      disease. Although it affects all systems, involvement of the vascular system is
      of vital importance. Pseudoaneurysm ruptures in the arteries are the major causes
      of sudden deaths in BD. Although pseudoaneurysms in aorta and pulmonary arteries
      are rare, it is even more rare in the subclavian arteries. In our case, a
      pulsatile mass in the right clavicular area was determined to be associated with
      BD and this case is presented because subclavian artery pseudoaneurysm is seen
      rarely in BD.

PMID- 16596322
TI  - A novel KCNQ4 one-base deletion in a large pedigree with hearing loss:
      implication for the genotype-phenotype correlation.
AB  - Autosomal-dominant, nonsyndromic hearing impairment is clinically and genetically
      heterogeneous. We encountered a large Japanese pedigree in which nonsyndromic
      hearing loss was inherited in an autosomal-dominant fashion. A genome-wide
      linkage study indicated linkage to the DFNA2 locus on chromosome 1p34. Mutational
      analysis of KCNQ4 encoding a potassium channel revealed a novel one-base deletion
      in exon 1, c.211delC, which generated a profoundly truncated protein without
      transmembrane domains (p.Q71fsX138). Previously, six missense mutations and one
      13-base deletion, c.211_223del, had been reported in KCNQ4. Patients with the
      KCNQ4 missense mutations had younger-onset and more profound hearing loss than
      patients with the 211_223del mutation. In our current study, 12 individuals with
      the c.211delC mutation manifested late-onset and pure high-frequency hearing
      loss. Our results support the genotype-phenotype correlation that the KCNQ4
      deletions are associated with later-onset and milder hearing impairment than the
      missense mutations. The phenotypic difference may be caused by the difference in
      pathogenic mechanisms: haploinsufficiency in deletions and dominant-negative
      effect in missense mutations.

PMID- 16596325
TI  - Timing of radiotherapy and survival benefit in breast cancer.
AB  - PURPOSE: To look at the optimum timing of radiotherapy in breast-conserving
      therapy (BCT) in relation to outcome in breast cancer. METHODS: We analyzed 1473
      BCT on 1446 breast cancer patients from our prospective cohort, stage I or II,
      node-negative, and without adjuvant systemic therapy. Timing was defined as time
      from lumpectomy till radiotherapy. Patients were categorized into three timing
      tertiles: 1-36 days, 37-53 days, and 54-112 days. RESULTS: The 10-year local
      relapse-free survival rates did not show significant differences between the
      three groups. The 10-year Distant Metastasis-Free Survival (DMFS) was 78.9% for
      the first tertile, versus 86.1% (HR 0.6; P = 0.009) for the second, and 90.7% (HR
      0.3; P < 0.001) for the third. The 10-year Disease-specific Survival (DSS) was
      83.8% for the first tertile, versus 90.6% (HR 0.5; P = 0.007) for the second, and
      97.2% (HR 02; P < 0.001) for the third. Also in multivariate Cox regression
      analysis the second (HR 0.6; P = 0.053) and the third tertile (HR 0.3; P = 0.002)
      had significantly better DSS. CONCLUSION: Timing of radiotherapy in BCT for
      breast cancer seems to be highly important in relation to survival. This study
      shows a 40-70% relative survival benefit with timing after 36 days.

PMID- 16596324
TI  - Leaf-shape variation of Paederia foetida in Japan: reexamination of the small,
      narrow leaf form from Miyajima Island.
AB  - Variations in Paederia foetida L. leaf shape were examined to evaluate the
      taxonomic validity of the small, narrow leaf form of P. foetida f. microphylla
      Honda from Miyajima Island, Honshu, Japan. There is considerable variation in P.
      foetida individuals in terms of leaf size and leaf index (leaf length:leaf width
      ratio). On Miyajima Island, some individuals have narrow leaves with a high leaf
      index value, a phenotype represented by the type specimen of P. foetida f.
      microphylla, and some do not. Given that the leaf size of individuals from
      Miyajima Island is smaller than that of individuals from other localities in
      Japan, and that the small leaf phenotype is stable even under cultivation, P.
      foetida f. microphylla is classified as the form having the smallest leaf size.
      Anatomical examination of leaf blades revealed that the large variation in leaf
      size was attributable to variation in the number of leaf cells but not to
      differences in cell size or cell shape. Based on these results, we discuss the
      endemism of P. foetida f. microphylla.

PMID- 16596323
TI  - Cancer genetics: colorectal cancer as a model.
AB  - Cancer is essentially a somatic evolutionary process and is, therefore,
      effectively defined by the genetic and epigenetic changes underlying this
      process. An understanding of the function of these changes is fundamental to
      devising new approaches to prevention and treatment. Colorectal cancer (CRC),
      apart from its obvious importance as one of the most frequent cancers, provides
      an excellent model for such studies because of the availability of precursor
      adenoma lesions and the existence of several clear-cut familial inherited
      susceptibilities. These include familial adenomatous polyposis (FAP), which led
      to the identification of the APC gene and the importance of the Wnt pathway, and
      hereditary non-polyposis CRC (HNPCC), which identified the role of the mismatch
      repair genes in colorectal and other cancers. The presently known range of
      genetic and epigenetic changes in CRCs and adenomas is reviewed in this paper and
      the evidence against a requirement for genomic instability presented, together
      with a discussion of patterns of gene methylation, including especially our work
      on the homeobox gene, CDX1. Clearly, familial cancers, such as FAP and HNPCC,
      cannot account for more than perhaps 5% of the incidence of CRC. There is,
      however, evidence that approximately a further 25-30% have some inherited
      susceptibility. Based on the association of APC missense variants with multiple
      adenomas, we proposed that much of this may be due to the cumulative effects of
      low frequency, low penetrance variants, and the "rare variant hypothesis". The
      evidence for this from our work on multiple adenoma cases, and certain other
      examples, is discussed.

PMID- 16596326
TI  - An intronic polymorphism associated with increased XRCC1 expression, reduced
      apoptosis and familial breast cancer.
AB  - XRCC1 coordinates the activities of DNA polymerase-beta and DNA ligase for base
      excision repair of oxidative DNA damage. In addition, there is some evidence that
      XRCC1 is a negative regulator of apoptosis. Single nucleotide polymorphisms in
      XRCC1 have been inconsistently associated with breast cancer risk. We evaluated
      XRCC1 gene expression in breast cancer cell lines and carcinogen-induced
      apoptosis in benign breast epithelial cells in relation to XRCC1 genotypes. XRCC1
      IVS10+141G>A was associated with increased expression of XRCC1 mRNA and protein,
      and reduced apoptosis in response to benzo-[a]-pyrene or ionizing radiation, but
      XRCC1 R399Q was not. These genotypes were also assessed in a clinic-based sample
      that included 190 breast cancer patients with a family history of breast cancer
      and 95 controls with no family history of breast cancer. Heterozygous XRCC1
      IVS10+141G>A was associated with an increased breast cancer risk (O.R. = 1.7, 95%
      C.I. 1.016-2.827, P = 0.04) as was homozygous XRCC1 IVS10+141G>A (O.R. = 4.7, 95%
      C.I. 1.028-21.444, P = 0.03). XRCC1 R399Q was not associated with breast cancer
      (O.R. 1.00, 95% C.I. 0.61-1.64). The XRCC1 IVS10+141G>A locus is centered in a
      sequence that is nearly identical to the consensus binding site for the PLAG1
      transcription factor. XRCC1 IVS10+141G>A is an intronic polymorphism that is
      associated with XRCC1 expression, apoptosis and familial breast cancer. It may
      occur within an intronic regulatory sequence.

PMID- 16596327
TI  - Catechol-O-methyltransferase haplotypes and breast cancer among women on Long
      Island, New York.
AB  - The gene encoding catechol-O-methyltransferase (COMT), critical to the
      inactivation of reactive catechol estrogens, has several single nucleotide
      polymorphisms (SNPs) that influence enzyme activity. A 3-SNP haplotype (IVS1+255
      C>T; Ex4-12 G>A; 3'UTR-521 A>G), which has been shown to reduce COMT expression
      in the human brain, has been identified. To evaluate the influence of genetic
      variation of COMT on breast cancer risk, these 3-SNPs were genotyped in 1052
      cases and 1098 controls. We estimated the associations between breast cancer and
      individual SNPs, as well as, multilocus haplotypes. We also examined surrogates
      of hormone exposure as potential modifiers of the putatively functional Ex4-12
      SNP-breast cancer association. Odds ratios (OR) and 95% confidence intervals (CI)
      were based on age-adjusted unconditional logistic regression models. We found no
      association between the individual SNPs alone and breast cancer. When examining
      the association between breast cancer and the 3-SNP haplotypes, we observed a 19%
      increase in risk associated with each copy of the TGG haplotype (OR=1.19, 95% CI
      0.96-1.49), relative to the common TAA haplotype, which was statistically
      significant when assuming a dominant model (OR=1.32, 95% CI 1.05-1.67, p
      value=0.02). In this report of COMT haplotypes and breast cancer, we found some
      evidence that additional genetic variability beyond the Ex4-12 G>A SNP
      contributes to risk of breast cancer among a small subgroup of women; however,
      these results need to be replicated in additional studies.

PMID- 16596328
TI  - Cowpea aphid-borne mosaic virus (CABMV) is widespread in passionfruit in Brazil
      and causes passionfruit woodiness disease.
AB  - Leaf samples of yellow passionfruit (Passiflora edulis f. flavicarpa) displaying
      fruit woodiness symptoms were collected in seven Brazilian states and the Federal
      District. Viral infection was confirmed by host range and ELISA, and fourteen
      viral isolates were obtained. All isolates were capable of infecting several
      leguminous host species, although differences in symptom severity were
      noticeable. Woodiness symptoms were reproduced in yellow passionfruit, and mosaic
      symptoms were induced in common bean. All isolates infected cowpea, reported as a
      non-host of passion fruit woodiness virus (PWV). Indirect ELISA demonstrated that
      all isolates were serologically related to each other and also to cowpea aphid
      borne mosaic virus (CABMV). The complete sequence of the capsid protein was
      determined for all isolates. Comparison of these sequences with those of other
      potyviruses indicated the highest identity with CABMV isolates (85 to 94%).
      Identity with PWV isolates ranged from 54 to 70%. Phylogenetic analysis grouped
      all of the Brazilian isolates in a monophyletic cluster with the CABMV isolates,
      clearly distinct from the PWV isolates. Furthermore, this analysis demonstrated
      that a group of previously characterized isolates from Brazil that had been
      designated as PWV should be reclassified as CABMV. Together, these results
      provide unequivocal evidence that, in Brazil, passionfruit woodiness disease is
      primarily caused by CABMV. The presence of PWV in Brazil has yet to be confirmed.

PMID- 16596329
TI  - Molecular epidemiology of European brown hare syndrome virus in France between
      1989 and 2003.
AB  - Genetic diversity between French European brown hare syndrome (EBHS) viruses
      since the disease appeared has been evaluated. Nucleotide sequencing of the
      partial capsid protein genes of 169 EBHS viruses collected from various parts of
      France between 1989 and 2003, three reference strains, and a Greek EBHSV
      collected in 2002 revealed a maximum nucleotide divergence of 11.7%, indicating a
      high level of conservation between viruses. Two major groups were identified. The
      first group contained EBHS viruses collected since 1989 from different parts of
      France, the reference strains, and all of the viruses located in the far north of
      France. In this group, three genogroups were clearly identified as mainly related
      to their geographic origin. The distribution of the viruses suggests that the
      early viruses have not disappeared and have slowly evolved in their area of
      origin. The second group, supported by a significant bootstrap value, contained
      the Greek EBHSV with the French EBHS viruses collected between 1999 and 2003 from
      regions of southern France. It constitutes a newly identified genogroup. Our
      results demonstrate strong differences in genetic evolution between EBHSV and
      rabbit haemorrhagic disease virus, with persistence of the earlier EBHS viruses
      and interaction between the geographical and temporal distributions.

PMID- 16596330
TI  - Construction of an infectious cDNA clone of Ribgrass mosaic virus Shanghai
      isolate and its modification to express an epitope of Mycobacterium tuberculosis.
AB  - Infectious cDNA clones of the Shanghai isolate of Ribgrass mosaic virus (RMV)
      were produced by joining four overlapping cDNA fragments and also in a single
      step by long template PCR. After inoculation of Nicotiana glutinosa with either
      RNA transcripts or the cDNA under the control of the CaMV 35S promoter, plants
      developed typical symptoms, and viral coat protein could be detected in them by
      Western blot analysis. However, compared to plants inoculated with purified viral
      RNA, lesions were fewer and appeared more slowly. An epitope of the Mycobacterium
      tuberculosis 31-kDa protein was inserted at the C-terminus of the viral coat
      protein by PCR using two overlapping fragments. The modified clone was also
      infectious and the foreign epitope could be detected serologically in the
      electron microscope and by Western blot analysis. The results demonstrate the
      potential of RMV as a viral gene vector.

PMID- 16596331
TI  - Epigenetic mechanisms: a common theme in vertebrate and invertebrate memory
      formation.
AB  - In this review we address the idea that conservation of epigenetic mechanisms for
      information storage represents a unifying model in biology, with epigenetic
      mechanisms being utilized for cellular memory at levels from behavioral memory to
      development to cellular differentiation. Epigenetic mechanisms typically involve
      alterations in chromatin structure, which in turn regulate gene expression. An
      emerging idea is that the regulation of chromatin structure through histone
      acetylation and DNA methylation may mediate long-lasting behavioral change in the
      context of learning and memory. We find this idea fascinating because similar
      mechanisms are used for triggering and storing long-term 'memory' at the cellular
      level, for example when cells differentiate. An additional intriguing aspect of
      the hypothesis of a role for epigenetic mechanisms in information storage is that
      lifelong behavioral memory storage may involve lasting changes in the physical,
      three-dimensional structure of DNA itself.

PMID- 16596332
TI  - Mechanisms of memory stabilization and de-stabilization.
AB  - Memories become stabilized through a time-dependent process that requires gene
      expression and is commonly known as consolidation. During this time, memories are
      labile and can be disrupted by a number of interfering events, including
      electroconvulsive shock, trauma and other learning or the transient effect of
      drugs such as protein synthesis inhibitors. Once consolidated, memories are
      insensitive to these disruptions. However, they can again become fragile if
      recalled or reactivated. Reactivation creates another time-dependent process,
      known as reconsolidation, during which the memory is restabilized. Here we
      discuss some of the questions currently debated in the field of memory
      consolidation and reconsolidation, the molecular and anatomical requirements for
      both processes and, finally, their functional relationship.

PMID- 16596334
TI  - Dunces and da Vincis: the genetics of learning and memory in Drosophila.
AB  - Progress towards amelioration and eventual cure of human cognitive disorders
      requires understanding the molecular signaling mechanisms that normally govern
      learning and memory. The fly Drosophila melanogaster has been instrumental in the
      identification of molecules and signaling pathways essential for learning and
      memory, because genetic screens have produced mutants in these processes and the
      system facilitates integrated genetic, molecular, histological and behavioral
      analyses. We discuss the behavioral paradigms available to assess associative
      learning and memory in the fly, the contributions learning and memory mutants
      have made to our understanding of the molecular mechanisms that govern learning
      and memory, and predictions stemming from the nature of the affected genes.
      Furthermore, we consider the multiple well-established behavioral assays
      available and the powerful molecular genetics of the fly with regard to
      development of models of human cognitive disorders and their pharmacological
      treatment.

PMID- 16596333
TI  - Dynamic memory networks: dissecting molecular mechanisms underlying associative
      memory in the temporal domain.
AB  - The molecular mechanisms underlying the induction and maintenance of memory are
      highly dynamic and comprise distinct phases covering a time window from seconds
      to even a lifetime. Neuronal networks, which contribute to these processes, have
      been extensively characterized on various levels of analysis, and imaging
      techniques allow monitoring of both gross brain activity as well as functional
      changes in defined brain areas during the time course of memory formation. New
      techniques developed in honeybees and fruit flies even allow for manipulation of
      neuronal networks and molecular cascades in a short temporal domain while a
      living animal under observation acquires new associative memories. These
      advantages make honeybees and flies ideal organisms to study transient molecular
      events underlying dynamic memory processing in vivo. In this review we will focus
      on the temporal features of molecular processes in learning and memory formation,
      summarize recent knowledge and present an outlook on future developments.

PMID- 16596335
TI  - Molecular nodes in memory processing: insights from Aplysia.
AB  - Recent research in a variety of systems indicates that memory formation can
      involve the activation of a wide range of molecular cascades. In assessing this
      recent work it is clear that no single cascade is uniquely important for all
      forms of memory, nor is a single form of memory uniquely dependent on a single
      cascade. Rather, it appears that molecular networks are differentially engaged in
      the induction of various forms of memory. Despite this highly interactive array
      of possible cascades, specific 'molecular nodes' have emerged as critical
      regulatory points in memory formation. Functionally, these nodes can operate in
      two sequential steps, beginning with a convergence of inputs which coordinately
      influence the activation state of the node, in which the nature of stimulation
      determines the dynamics of nodal activity, followed by a divergence of substrate
      selection, in which the node serves as a gateway that activates specific
      downstream effectors. Finally, specific nodes can be differentially engaged (i.e.
      have different 'weights') depending upon the nature and pattern of the activating
      stimulus. The marine mollusk Aplysia has proven useful for a molecular analysis
      of memory formation. We will use this system to highlight some of the molecular
      strategies employed by the nervous system in the formation of memory for
      sensitization, and we will focus on extracellular signal-related kinase as a
      candidate node integral to these processes.

PMID- 16596337
TI  - Sialic acid-specific lectins: occurrence, specificity and function.
AB  - Sialic acids consist of a family of acidic nine-carbon sugars that are typically
      located at the terminal positions of a variety of glycoconjugates. Naturally
      occurring sialic acids show an immense diversity of structure, and this reflects
      their involvement in a variety of biologically important processes. One such
      process involves the direct participation of sialic acids in recognition events
      through specific interactions with lectins, a family of proteins that recognise
      and bind sugars. This review will present a detailed overview of our current
      knowledge regarding the occurrence, specificity and function of sialic acid
      specific lectins, particularly those that occur in viruses, bacteria and non
      vertebrate eukaryotes.

PMID- 16596338
TI  - Mitochondria and calpains mediate caspase-dependent apoptosis induced by
      doxycycline in HeLa cells.
AB  - Doxycycline (Dc) has been demonstrated to inhibit cell growth and induce
      apoptosis in tumor cells, although its mechanism of action is not fully
      understood. The present study demonstrates that apoptosis can be induced in HeLa
      cells. Western blot data demonstrated that cytochrome c (Cyt c), Smac (the second
      mitochondria-derived activator of caspase), calpain I, caspase-9, -3 and -8 were
      involved in the apoptotic process, while the pan caspase inhibitor zVAD-fmk
      almost completely inhibited Dc-induced apoptosis. We further demonstrated that
      the release of mitochondrial proteins and the activation of calpains occurred
      upstream of the caspase cascade, in which caspase-9 was activated in response to
      the release of Cyt c, that caspase-8 activation was caspase and calpain
      dependent, and that caspase-3 was activated mainly by caspase-8 and -9. Caspase-8
      played important roles in the activation of caspase-3 and induction of apoptosis,
      whereas the role of the caspase-9 was limited.

PMID- 16596339
TI  - Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial
      growth factor through the activation of epidermal growth factor receptor, MEK/
      ERK1,2 and PI3K/Akt.
AB  - The E5 oncoprotein of human papillomavirus (HPV) 16 plays an important role in
      early cervical carcinogenesis. Vascular endothelial growth factor (VEGF) plays a
      central role in switching on the angiogenic phenotype during early cervical
      carcinogenesis. However, the relationship between E5 and VEGF has not previously
      been examined. To clarify the regulatory role of E5 in VEGF expression, we
      transferred the E5 gene into various cell types. E5 increased VEGF expression.
      The addition of epidermal growth factor receptor (EGFR) inhibitor significantly
      suppressed VEGF expression, demonstrating that E5 stimulates VEGF expression
      through the activation of EGFR. E5-mediated EGFR activation was accompanied by
      phosphorylation of Akt and ERK1/2, which are also involved in VEGF expression.
      Furthermore, the mRNA stability of VEGF was not affected by E5, but VEGF promoter
      activity could be modulated by inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt
      pathways in E5-expressing cells. Collectively, these novel results suggest that
      HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1/2 and PI3K/Akt.

PMID- 16596340
TI  - Decoding the Hedgehog signal in animal development.
AB  - The Hedgehog (Hh) family of secreted proteins plays essential roles in a myriad
      of developmental processes via a complex signaling cascade conserved in species
      ranging from insects to mammals. In many developmental contexts, Hh acts as long
      range morphogen to control distinct cellular outcomes as a function of its
      concentration. Here we review the current understanding of the Hh signaling
      mechanisms that govern the establishment of the Hh gradient and the transduction
      of the Hh signal with an emphasis on the intracellular signaling cascade from the
      receptor to the nuclear effector. We discuss how graded Hh signals are transduced
      to govern distinct developmental outcomes.

PMID- 16596342
TI  - NMR assignment of the outer membrane lipoprotein (OmlA) from Xanthomonas
      axonopodis pv citri.

PMID- 16596343
TI  - Chemical shift backbone assignments of TAP-N, the 31 kDa cargo-binding region of
      the protein TAP.

PMID- 16596344
TI  - Chemical shift assignments of Leishmania mexicana ICP, a novel cysteine peptidase
      inhibitor.

PMID- 16596345
TI  - The effects of prey patchiness, predator aggregation, and mutual interference on
      the functional response of Phytoseiulus persimilis feeding on Tetranychus urticae
      (Acari: Phytoseiidae, Tetranychidae).
AB  - The spatial distributions of two-spotted spider mites Tetranychus urticae and
      their natural enemy, the phytoseiid predator Phytoseiulus persimilis, were
      studied on six full-grown cucumber plants. Both mite species were very patchily
      distributed and P. persimilis tended to aggregate on leaves with abundant prey.
      The effects of non-homogenous distributions and degree of spatial overlap between
      prey and predators on the per capita predation rate were studied by means of a
      stage-specific predation model that averages the predation rates over all the
      local populations inhabiting the individual leaves. The empirical predation rates
      were compared with predictions assuming random predator search and/or an even
      distribution of prey. The analysis clearly shows that the ability of the
      predators to search non-randomly increases their predation rate. On the other
      hand, the prey may gain if it adopts a more even distribution when its density is
      low and a more patchy distribution when density increases. Mutual interference
      between searching predators reduces the predation rate, but the effect is
      negligible. The stage-specific functional response model was compared with two
      simpler models without explicit stage structure. Both unstructured models yielded
      predictions that were quite similar to those of the stage-structured model.

PMID- 16596346
TI  - Previous and present diets of mite predators affect antipredator behaviour of
      whitefly prey.
AB  - Predator diet is known to influence antipredator behaviour in prey. Yet, it is
      not clear how antipredator behaviour is affected by diet changes of the predator.
      We studied the effect of previous and present diet of a predatory mite
      Typhlodromips swirskii on the antipredator response of its prey, the whitefly
      Bemisia tabaci. An earlier study showed that adult female whiteflies that had
      experienced predators, had learned to avoid ovipositing on plants with predators
      whose previous and present diet consisted of whitefly eggs and immatures. Here,
      we investigate whether adult whiteflies also avoid plants with predators whose
      present and/or previous diet consisted of a non-whitefly food source. Adult
      whiteflies were found not to avoid plants with predators whose present diet
      consisted of pollen and whose previous diet had consisted of either pollen or
      whitefly eggs and larvae. They did avoid plants with predators whose present diet
      consisted of whiteflies and whose previous diet had consisted of pollen, but to a
      lesser extent than when previous and present diet consisted of whiteflies. In a
      choice experiment, whiteflies discriminated between plants with predators whose
      present diet consisted of whiteflies, but that differed in previous diet. Our
      results show that both previous and present diets of predators are important in
      eliciting antipredator behaviour.

PMID- 16596348
TI  - Testing for non-target effects of spinosad on twospotted spider mites and their
      predator Phytoseiulus persimilis under greenhouse conditions.
AB  - The compatibility of the selective insecticide spinosad (Conserve SC), at rates
      recommended for thrips control in greenhouses, with release of the predatory mite
      Phytoseiulus persimilis Athias-Henriot (Acari: Phytoseiidae) to control spider
      mites, was investigated in a crop of ivy geranium Pelargonium peltatum, cultivar
      'Amethyst 96.' Plants were inoculated with twospotted spider mites, Tetranychus
      urticae Koch (Acari: Tetranychidae), 2 weeks before treatments were applied.
      There were three treatment variables, each at two levels: predators (released or
      not), spray application (water or Conserve SC at 2 ml/3.79 l), and timing of
      spray (1 day before or after predators were released). Twospotted spider mite
      populations then were sampled twice each week over a three-week period. The
      application or timing of spinosad had no effect on the ability of the predator to
      reduce the population of spider mites. Spider mite populations in the no-predator
      treatment continued to expand over the course of the experiment, while those in
      the predator-release treatment declined. We conclude that P. persimilis can be
      used in conjunction with spinosad on ivy geraniums without causing obvious
      detrimental effects to this predator or leading to a reduction in biological
      control.

PMID- 16596347
TI  - Assessing the effects of Bt Maize on the predatory mite Neoseiulus cucumeris.
AB  - The investigation of Neoseiulus cucumeris in the context of the ecological risk
      assessment of insect resistant transgenic plants is of particular interest as
      this omnivorous predatory mite species is commercially available and considered
      important for biological control. In a multitrophic feeding experiment we
      assessed the impact of Bt maize on the performance of N. cucumeris when offered
      spider mites (Tetranychus urticae) reared on Bt (Bt11, Syngenta) or non-Bt maize
      (near isogenic line) and Bt or non-Bt maize pollen as a food source. Various
      parameters including mortality, development time, oviposition rate were measured.
      Spider mites were used as a prey for N. cucumeris, since these herbivores are
      known to contain similar levels of Cry1Ab toxin, when reared on Bt maize, as
      those found in the transgenic leaf material. In contrast, toxin levels in pollen
      of this transgenic cultivar are very low. No differences in any of the parameters
      were found when N. cucumeris was fed with spider mites reared on Bt and non-Bt
      maize. Pollen was shown to be a less suitable food source for this predator as
      compared to spider mites. Moreover, subtle effects on female N. cucumeris (9%
      longer development time and 17% reduced fecundity) were measured when fed with
      pollen originating from Bt maize as compared to non-Bt maize pollen. Our findings
      indicate that the predatory mite N. cucumeris is not sensitive to the Cry1Ab
      toxin as no effects could be detected when offered Bt-containing spider mites,
      and that the effects found when fed with Bt maize pollen can be assigned to
      differences in nutritional quality of Bt and non-Bt maize pollen. The
      significance of these findings is discussed with regard to the ecological
      relevance for risk assessment of transgenic plants.

PMID- 16596349
TI  - Evaluation of resistance pattern to fenpyroximate and pyridaben in Tetranychus
      urticae collected from greenhouses and apple orchards using lethal concentration
      slope relationship.
AB  - This study aimed to monitor the present and future developments of the resistance
      of Tetranychus urticae Koch to fenpyroximate and pyridaben, using the
      relationship of the LC(50) and slope of the concentration-mortality line in a
      probit model, for the provision of reliable resistance management tactics.
      Tetranychus urticae populations were collected from 16 commercial greenhouses,
      where various crops were cultivated, as well as from 10 apple orchards throughout
      Korea. The resistance to fenpyroximate and pyridaben of each population was
      estimated by calculating the median lethal concentration (LC(50)), resistance
      ratio (RR) and slope of the concentration-mortality regression. Most of the
      greenhouse populations exhibited moderate levels of resistance, whereas the apple
      orchard populations showed only low levels, indicating that T. urticae
      populations in greenhouses were more strongly selected than those in apple
      orchards. Four population groups were established based on either the habitats
      (greenhouse and apple orchard) or acaricides (fenpyroximate and pyridaben). To
      test the hypothesis, "the slope is greatest at low and high levels of
      resistance," the slopes were regressed as a function of the LC(50), and fitted to
      a polynomial regression. The polynomial regression model explained this
      relationship well for the four population groups (p < 0.05), indicating that the
      development of resistance toward fenpyroximate or pyridaben was consistent with
      the gradient. A laboratory selection study agreed with the results from both
      acaricide field populations. These results suggest that the gradient was a good
      indicator of the susceptibility of T. urticae to genetic variations, which was
      related to the LC(50). The application of these findings is also discussed in
      relation to the resistance management of T. urticae.

PMID- 16596350
TI  - Laboratory studies on the use of two new arenas to evaluate the impact of the
      predatory mites Blattisocius tarsalis and Cheyletus eruditus on residual
      populations of the stored product mite Acarus siro.
AB  - Residual populations of storage mites sheltering in crevices and cracks escape
      conventional control treatments and are implicated in the infestation of newly
      harvested grain. In a series of 24 h laboratory tests, the performance of
      solitary adults of two predatory mite species, Cheyletus eruditus (Schrank) and
      Blattisocius tarsalis (Berlese), were assessed for controlling small numbers of
      the flour mite Acarus siro (L.). Tests were carried out in the presence or
      absence of prey refuges or grain debris to afford shelter to the flour mites.
      While C. eruditus had a significant effect on the motile stages of A. siro, in
      contrast B. tarsalis had a significant effect on the eggs. The maximum percentage
      of motile stages of A. siro eaten by C. eruditus was 82%, whereas the minimum
      percentage of A. siro eggs eaten by B. tarsalis was 99%. While the performance of
      C. eruditus in predating on motile stages of the flour mite was hindered by the
      presence of the prey refuge (38% eaten) and grain debris (25% eaten), the
      performance of B. tarsalis in predating on flour mite eggs was unaffected (100%
      eaten in presence of prey refuge or grain debris). In prolonged exposures (36
      days) the performance of 2, 4 or 8 adult predators, either a single species or a
      combination of both, was assessed for their ability to control a population of
      the flour mite developing up to F(2) from an initial inoculum of 80 females and
      20 males, allowed to oviposit for 72 h in the absence of predatory mites. The
      maximum reduction in prey population of 80% was achieved with eight B. tarsalis.
      Combining the two predatory species did not enhance the reduction of A. siro
      population.

PMID- 16596351
TI  - Rickettsial agents from parasitic dermanyssoidea (Acari: Mesostigmata).
AB  - Mites are often overlooked as vectors of pathogens, but have been shown to harbor
      and transmit rickettsial agents such as Rickettsia akari and Orientia
      tsutsugamushi. We screened DNA extracts from 27 mites representing 25 species of
      dermanyssoids for rickettsial agents such as Anaplasma, Bartonella, Rickettsia,
      and Wolbachia by PCR amplification and sequencing. DNA from Anaplasma spp., a
      novel Bartonella sp., Spiroplasma sp., Wolbachia sp., and an unclassified
      Rickettsiales were detected in mites. These could represent mite-borne bacterial
      agents, bacterial DNA from blood meals, or novel endosymbionts of mites.

PMID- 16596352
TI  - Comparison of preservation methods of Rhipicephalus appendiculatus (Acari:
      Ixodidae) for reliable DNA amplification by PCR.
AB  - Five differently preserved groups of adult Rhipicephalus appendiculatus specimens
      were compared for quality of DNA extracted. Three methods were used to extract
      DNA from specimens i.e. two simple mosquito validated DNA extraction methods and
      a tick validated method. Extraction of DNA from tick legs was attempted. The
      quality of DNA extracted was evaluated by the success of PCR amplification of the
      ITS2 gene and the mitochondrial COI gene fragment. Fresh specimens (i.e. killed
      just before extraction) had the highest success of DNA amplification followed by
      specimens killed in ethanol and subsequently stored in the refrigerator (4
      degrees C). There was no significant difference in amplification success between
      cryopreserved and 70% ethanol preserved specimens. It was possible to amplify DNA
      from legs of ticks. Sequenced ITS2 amplicon of template obtained from legs of
      ticks was as legible as those from whole tick extract. The two mosquito validated
      DNA extraction methods showed a significantly lower amplification success than
      the tick validated protocol.

PMID- 16596353
TI  - Physiological age of field-collected female taiga ticks, Ixodes persulcatus
      (Acari: Ixodidae), and their infection with Borrelia burgdorferi sensu lato.
AB  - In some studies the prevalence of tick infection (infection rate) and the
      intensity of infection are negatively correlated with unfed tick age (in the
      broad sense of this term). However, no special research has been carried out to
      consider the phenomenon thoroughly. The infection indices of the female taiga
      ticks, Ixodes persulcatus, infected with Borrelia burgdorferi s.l. were related
      to tick physiological age, an index that more precisely reflects tick
      physiological state than the time of tick collection in the field or the duration
      of tick survival under laboratory conditions. A novel quantitative technique of
      physiological age determination based on the evaluation of the ratios between
      sizes of the stable (scutum) and the changing (alloscutum) structures of the tick
      body was used. The age was estimated in accordance with the classical age-grade
      scale introduced by Balashov and a more fractional scale determined by the new
      technique. In total, 131 female ticks were examined for their infection and
      physiological age, 46 of which were infected with B. burgdorferi s.l. (mean
      infection rate 35.1%). The minimal intensity of infection was 0.4 bacterial cells
      per 100 fields of view whereas the maximal infection was 172 cells. There was no
      difference between the prevalence of infection in ticks of different
      physiological age. The intensity of infection obviously differed between ticks of
      different age groups in the scale introduced by Balashov but did not
      significantly differ between ticks of different age groups according to the
      fractional age-grade scale. The data concerning the relationships between
      Borrelia burgdorferi and unfed Ixodes ticks are considered.

PMID- 16596354
TI  - Performance of a prototype baited-trap in attracting and infecting the tick
      Amblyomma variegatum (Acari: Ixodidae) in field experiments.
AB  - Investigations were commenced to study the potential use of the fungi, Beauveria
      bassiana, Metarhizium anisopliae, and the attraction-aggregation-attachment
      pheromone (AAAP) for the control of Ambloyomma variegatum as an environmentally
      friendly technology. The objective of the study was to develop and test a device,
      which could be used for pheromone and carbon dioxide delivery and infection of
      ticks with the fungi in an attempt to control the tick populations in the
      vegetation. Using a pheromone-baited device treated with the fungi mixture, 79%
      of the ticks released were attracted and exposed to the fungi and of these, 78%
      died during incubation in the laboratory. In another set of experiments, of the
      released ticks that were similarly exposed to fungi using the pheromone-baited
      device and left in the vegetation, 33.8% were recovered compared to recoveries of
      between 76 and 84% in the controls. These results were significantly different at
      the 5% level, an indication that the pheromone/fungi mixtures had significant
      effect in reducing the tick population in the field.

PMID- 16596355
TI  - The known distribution and ecological preferences of the tick subgenus Boophilus
      (Acari: Ixodidae) in Africa and Latin America.
AB  - A compilation of the known distribution of Boophilus ticks in Africa and Latin
      America is presented, together with details on climate preferences. B. annulatus
      is recorded mainly in the western part of a strip from the equator to parallel 20
      degrees N. It associates with woodlands and forests (lowland rain forest and
      secondary grassland). This species is also present in the Mediterranean region,
      associated to woodland and open areas. B. decoloratus extends southern to
      parallel 20 degrees N, in woodland with montane vegetation and Zambezian miombo;
      some records have been collected in the highveld grassland. B. geigyi is mainly
      collected in the western range of a stripe extending between parallels 5 degrees
      N and 18 degrees N, associated with Sudanian woodland, lowland rain forest with
      secondary grassland and woodland. Confirmed records of microplus in Africa are
      restricted to Malagasy region and south and eastern Africa, being predominant in
      the Zambezian miombo, deciduous forest with secondary grassland, and woodland. In
      Latin America, microplus is abundant in the Mesoamerican corridor to Venezuela
      and Colombia, and southern in Brazil and Argentina. The tick is mainly associated
      to the biomes of Chaco and Pampas in Argentina, the North-central moist Andes,
      the Atlantic forest (southern range) and the moist Meso-American vegetation
      (northern range). Most collections of B. annulatus and B. geigyi came from areas
      where winter minimum temperature is above 15 degrees C, maximum temperatures
      remain between 33 and 36 degrees C and maximum rainfall is recorded between June
      and September. B. decoloratus and African B. microplus are recorded in sites with
      low temperatures in May-September. Minimum temperature requirements are similar
      for both B. decoloratus and African B. microplus, and both are around 4 degrees C
      less than the value recorded for collections of Latin-American B. microplus. The
      rainfall pattern observed for decoloratus shows a minimum in May and June. The
      requirements of total rainfall are highest for B. microplus in Latin America,
      while records of African B. microplus are concentrated in areas of low rainfall
      between May and October, and high rainfall between November and March (low
      rainfall in the same period for B. decoloratus). Statistical analysis revealed
      the existence of populations (demes) with ecologically different requirements
      within each tick species. Both B. annulatus and B. decoloratus showed many
      different demes clearly associated to defined areas. The collections of Latin
      American B. microplus are very homogeneous according climate preferences and well
      separated from the African counterpart.

PMID- 16596356
TI  - Clinical significance of bacteriuria with low colony counts of Enterococcus
      species.
AB  - The clinical significance of low counts of enterococci in urine cultures remains
      unclear. The goal of this study was to investigate the clinical significance of
      enterococci growing in numbers lower than 100,000 colony-forming units per
      milliliter (cfu/ml) in urine samples. Clinical parameters were collected from
      patients whose midstream clean-catch urine samples grew Enterococcus spp. in
      amounts between >or=10,000 and 100,000 cfu/ml and who were not previously treated
      with antibiotics. Only those patients who had leukocyturia in addition to
      positive culture were considered to have true urinary tract infection (UTI). Of
      the 208 patients included in the study, 54% were diagnosed with true UTI.
      Patients with true UTI were older by 6 years (p=0.03), were more likely to be
      hospitalized (p=0.016), had higher rates of dysuria (p=0.0001), urgency
      (p=0.0001), and frequency (p=0.0001), and had more solid tumors (p=0.03). By
      multivariate analysis, urgency (OR=7.1) and hospitalization (OR=4.4) were
      identified as independent risk factors for true UTI with enterococci in low
      counts. Enterococcal counts in patients with true UTI were randomly distributed
      all along the scale between 10,000 and 100,000 cfu/ml, and no differential cutoff
      could be determined. In conclusion, more than half of the patients whose urine
      cultures grow Enterococcus spp. in counts lower than 100,000 cfu/ml may have true
      UTI, especially if they are hospitalized and have symptoms of dysuria, urgency,
      or frequency. Microbiology laboratories should perform a complete work-up on
      samples containing low counts of enterococci, and the final interpretation should
      be done by physicians, using additional clinical information.

PMID- 16596357
TI  - Inability of HDL from type 2 diabetic patients to counteract the inhibitory
      effect of oxidised LDL on endothelium-dependent vasorelaxation.
AB  - AIMS/HYPOTHESIS: In healthy normolipidaemic and normoglycaemic control subjects,
      HDL are able to reverse the inhibition of vasodilation that is induced by
      oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride
      rich than in control subjects. These alterations are likely to modify the
      capacity of HDL to reverse the inhibition of vasodilation induced by oxidised
      LDL. SUBJECTS AND METHODS: Using rabbit aorta rings, we compared the ability of
      HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the
      inhibition of vasodilation that is induced by oxidised LDL. RESULTS: Oxidised LDL
      inhibited endothelium-dependent vasodilation (maximal relaxation [Emax] = 58.2+/
      14.6 vs 99.3+/-5.2% for incubation without any lipoprotein, p < 0.0001). HDL from
      control subjects significantly reduced the inhibitory effect of oxidised LDL on
      vasodilatation (Emax = 77.6+/-12.9 vs 59.5+/-7.7%, p < 0.001), whereas HDL from
      type 2 diabetic patients had no effect (Emax = 52.4+/-20.4 vs 57.2+/-18.7%, NS).
      HDL triglyceride content was significantly higher in type 2 diabetic patients
      than in control subjects (5.3+/-2.2 vs 3.1+/-1.4%, p < 0.01) and was highly
      inversely correlated to Emax for oxidised LDL+HDL in type 2 diabetic patients (r
      = -0.71, p < 0.005). CONCLUSIONS/INTERPRETATION: In type 2 diabetes mellitus, the
      ability of HDL to counteract the inhibition of endothelium-dependent
      vasorelaxation induced by oxidised LDL is impaired and is inversely correlated
      with HDL triglyceride content. These findings suggest that HDL are less
      atheroprotective in type 2 diabetic patients than in control subjects.

PMID- 16596358
TI  - Comparison of the pharmacokinetics and pharmacodynamics of biphasic insulin
      aspart and insulin glargine in people with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: The pharmacokinetic and pharmacodynamic properties of biphasic
      insulin aspart (BIAsp 30) (30% soluble, 70% protaminated insulin aspart [IAsp])
      and insulin glargine (IGlarg) were compared. METHODS: Twelve people with type 2
      diabetes took part in two 24-h isoglycaemic clamp studies, 1 week apart. Patients
      were randomised to treatment with 0.5 U/kg of BIAsp 30 (0.25 U/kg at 08.30 h and
      0.25 U/kg at 20.30 h) or 0.50 U/kg IGlarg at 08.30 h. Both insulins were given by
      subcutaneous injection into the anterior abdominal wall. The plasma glucose,
      glucose infusion rates, plasma insulin and C-peptide concentrations were
      measured. RESULTS: All 12 patients were men; mean (+/-SD) age was 58.8 (8.9)
      years, BMI 31.0 (3.0) kg/m2 and HbA(1c) 7.1 (0.6)%. Plasma glucose was constant
      throughout the 24-h clamp period. After each injection of BIAsp 30, glucose
      infusion rates increased, reaching a distinct peak approximately 3-5 h after
      injection. A much flatter postinjection profile was observed following IGlarg
      administration. Plasma insulin concentrations rose rapidly after each injection
      of BIAsp 30, reaching a distinct peak after approximately 2-3 h. A flatter plasma
      insulin profile reached a plateau approximately 6-16 h after IGlarg
      administration. Plasma C-peptide fell below baseline after both injections of
      BIAsp 30 but remained unaltered after IGlarg injection.
      CONCLUSIONS/INTERPRETATION: The pharmacodynamic and pharmacokinetic profiles were
      34 and 28%, respectively, higher following equivalent doses (0.5 U/kg) of BIAsp
      30 given as two split doses than following IGlarg given as a single daily dose.

PMID- 16596359
TI  - Age at introduction of new foods and advanced beta cell autoimmunity in young
      children with HLA-conferred susceptibility to type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Evidence for the role of infant feeding in the development of
      beta cell autoimmunity is inconsistent. We set out to study the effects of
      breastfeeding and of age at introduction of supplementary foods on the
      development of beta cell autoimmunity. SUBJECTS AND METHODS: A prospective birth
      cohort of 3,565 infants with HLA-DQB1-conferred susceptibility to type 1 diabetes
      was recruited between 1996 and 2001 from two university hospital areas in
      Finland. Blood samples were collected at 3- to 12-month intervals to measure
      antibodies against islet cells, insulin, glutamate dehydroxylase and islet
      antigen 2. The families kept a record on the age at introduction of new foods,
      and for each visit completed a structured dietary questionnaire. The endpoint was
      repeated positivity for islet cell antibodies together with at least one of the
      other three antibodies. RESULTS: The overall or exclusive duration of
      breastfeeding was not associated with the risk of developing the endpoint. An
      early age at introduction of fruits and berries (< or =4 months) was related to
      increased risk of developing positivity for the endpoint (hazard ratio [95% CI]
      for earliest tertile 2.02 [1.03-3.95] and for midtertile 1.97 [1.06-3.64]
      compared with latest tertile >4 months). Also, introducing roots between 3 and
      3.9 months (midtertile) was related to increased risk of the endpoint (hazard
      ratio [95% CI] for the earliest tertile 1.04 [0.57-1.90] and for midtertile 1.82
      [1.19-2.79] compared with latest tertile). These associations were independent of
      several putative socio-demographic and perinatal confounding factors.
      CONCLUSIONS/INTERPRETATION: Our findings suggest that an early age at
      introduction of fruits and berries and roots associates independently with beta
      cell autoimmunity, contradicting earlier findings from smaller birth cohort
      studies.

PMID- 16596362
TI  - [Future cancer incidents in Germany].
AB  - The future as well as the past development of cancer incidents in Germany is of
      continuous importance for health policy. Cancer incidence data observed over more
      than 20 years are analysed by log-linear models with polynomial trend components.
      The estimated trend models are used for a trend extrapolation until the year
      2020. Since cancer registration in Germany is not complete yet and does not cover
      the whole area of the country national incidences are estimated by the data of
      the existing complete regional cancer registries. In this way it can be assessed
      that the number of new cancer diseases increased from 270,000 cases in 1980 to
      420,000 cases in 2002. Extrapolating the trends and taking into account the
      demographic prognosis of the German Federal Statistical Office 570,000 (version
      1) or 590,000 (version 9) annual cancer cases are predicted for the year 2020.
      From 1980 to 2002 a decrease of cancer mortality was observed. If this trend
      continues until 2020, the number of deaths caused by cancer would decrease from
      209,000 in 2002 to 153,000 (or 158,000) in 2020, although the number of cancer
      cases are predicted to increase. Assuming constant mortality rates the number of
      deaths caused by cancer would be much higher.

PMID- 16596363
TI  - [Pathogenesis, diagnosis and therapy of Legionella infections].
AB  - Legionella species are ubiquitous in aquatic environments. About 50 years ago
      they entered the engineered (technical) environment, i.e. warm water systems with
      zones of stagnation. Since that time they represent a hygienic problem. After
      transmission to humans via aerosols legionellae might cause Legionella pneumonia
      (legionnaires' disease) or influenza-like respiratory infections (Pontiac fever).
      Epidemiological data suggest that Legionella strains might differ substantially
      in their virulence properties. Although the molecular basis is not understood L.
      pneumophila serogroup 1 especially MAb 3/1-positive strains cause the majority of
      infections. The main virulence feature is the ability to multiply
      intracellularly. After uptake into macrophages legionellae multiply in a
      specialized vacuole and finally lyse their host cells. Several bacterial factors
      like surface components, secretion systems and iron uptake systems are involved
      in this process. Since the clinical picture of Legionella pneumonia does not
      allow differentiation from pneumoniae caused by other pathogens, microbiological
      diagnostic methods are needed to establish the diagnosis. Cultivation of
      legionellae from clinical specimens, detection of antigens and DNA in patients'
      samples and detection of antibodies in serum samples are suitable methods.
      However, none of the diagnostic tests presently available offers the desired
      quality with respect to sensitivity and specificity. Therefore, the standard
      technique is to use several diagnostic tests in parallel. Advantages and
      disadvantages of the diagnostic procedures are discussed. Therapeutic options for
      Legionella infections are newer macrolides like azithromycin and chinolones
      (ciprofloxacin, levofloxacin and moxifloxacin).

PMID- 16596361
TI  - Differential effects of monounsaturated, polyunsaturated and saturated fat
      ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in
      overweight and obese, non-diabetic humans.
AB  - AIMS/HYPOTHESIS: Prolonged elevation of plasma specific fatty acids may exert
      differential effects on glucose-stimulated insulin secretion (GSIS), insulin
      sensitivity and clearance. SUBJECTS AND METHODS: We examined the effect of oral
      ingestion, at regular intervals for 24 h, of an emulsion containing either
      predominantly monounsaturated (MUFA), polyunsaturated (PUFA) or saturated (SFA)
      fat or water (control) on GSIS, insulin sensitivity and insulin clearance in
      seven overweight or obese, non-diabetic humans. Four studies were conducted in
      each individual in random order, 4-6 weeks apart. Twenty-four hours after
      initiation of oral ingestion, subjects underwent a 2 h, 20 mmol/l hyperglycaemic
      clamp to assess GSIS, insulin sensitivity and insulin clearance. RESULTS:
      Following oral ingestion of any of the three fat emulsions over 24 h, plasma
      NEFAs were elevated by approximately 1.5- to 2-fold over the basal level.
      Ingestion of any of the three fat emulsions resulted in reduction in insulin
      clearance, and SFA ingestion reduced insulin sensitivity. PUFA ingestion was
      associated with an absolute reduction in GSIS, whereas insulin secretion failed
      to compensate for insulin resistance in subjects who ingested SFA.
      CONCLUSIONS/INTERPRETATION: Oral ingestion of fats with differing degrees of
      saturation resulted in different effects on insulin secretion and action. PUFA
      ingestion resulted in an absolute reduction in insulin secretion and SFA
      ingestion induced insulin resistance. Failure of insulin secretion to compensate
      for insulin resistance implies impaired beta cell function in the SFA study.

PMID- 16596360
TI  - Proinsulin in development: New roles for an ancient prohormone.
AB  - In postnatal organisms, insulin is well known as an essential anabolic hormone
      responsible for maintaining glucose homeostasis. Its biosynthesis by the
      pancreatic beta cell has been considered a model of tissue-specific gene
      expression. However, proinsulin mRNA and protein have been found in embryonic
      stages before the formation of the pancreatic primordium, and later, in
      extrapancreatic tissues including the nervous system. Phylogenetic studies have
      also confirmed that production of insulin-like peptides antecedes the
      morphogenesis of a pancreas, and that these peptides contribute to normal
      development. In recent years, other roles for insulin distinct from its metabolic
      function have emerged also in vertebrates. During embryonic development, insulin
      acts as a survival factor and is involved in early morphogenesis. These findings
      are consistent with the observation that, at these stages, the proinsulin gene
      product remains as the precursor form, proinsulin. Independent of its low
      metabolic activity, proinsulin stimulates proliferation in developing
      neuroretina, as well as cell survival and cardiogenesis in early embryos.
      Insulin/proinsulin levels are finely regulated during development, since an
      excess of the protein interferes with correct morphogenesis and is deleterious
      for the embryo. This fine-tuned regulation is achieved by the expression of
      alternative embryonic proinsulin transcripts that have diminished translational
      activity.

PMID- 16596364
TI  - [The Canadian experience with methods of systematic assessment of performance and
      revalidation in medicine. Chances for Germany].
AB  - Recertification and systematic assessment of performance are components of well
      developed medical quality culture. Canada has accumulated a wealth of experience
      in the development and application of methods of assessment. Germany can learn
      from the Canadian experience. In this article the Canadian three-step approach to
      assessment is introduced as well as the experience of its implementation in the
      provinces of Ontario and Alberta.

PMID- 16596367
TI  - Towards numerical forecasting of long-range air transport of birch pollen:
      theoretical considerations and a feasibility study.
AB  - This paper considers the feasibility of numerical simulation of large-scale
      atmospheric transport of allergenic pollen. It is shown that at least small
      grains, such as birch pollen, can stay in the air for a few days, which leads to
      a characteristic scale for their transport of approximately 10(3) km. The
      analytical consideration confirmed the applicability of existing dispersion
      models to the pollen transport task and provided some reference parameterizations
      of the key processes, including dry and wet deposition. The results were applied
      to the Finnish Emergency Dispersion Modelling System (SILAM), which was then used
      to analyze pollen transport to Finland during spring time in 2002-2004. Solutions
      of the inverse problems (source apportionment) showed that the main source areas,
      from which the birch flowering can affect Finnish territory, are the Baltic
      States, Russia, Germany, Poland, and Sweden-depending on the particular
      meteorological situation. Actual forecasting of pollen dispersion required a
      birch forest map of Europe and a unified European model for birch flowering, both
      of which were nonexistent before this study. A map was compiled from the national
      forest inventories of Western Europe and satellite images of broadleaf forests.
      The flowering model was based on the mean climatological dates for the onset of
      birch forests rather than conditions of any specific year. Utilization of
      probability forecasting somewhat alleviated the problem, but the development of a
      European-wide flowering model remains the main obstacle for real-time forecasting
      of large-scale pollen distribution.

PMID- 16596365
TI  - Perturbation of endothelial junction proteins by Staphylococcus aureus alpha
      toxin: inhibition of endothelial gap formation by adrenomedullin.
AB  - Endothelial hyperpermeability is a hallmark of an inflammatory reaction and
      contributes to tissue damage in severe infections. Loss of endothelial cell-cell
      adhesion leads to intercellular gap formation allowing paracellular fluid flux.
      Although Staphylococcus aureus alpha-toxin significantly contributed to
      staphylococci disease, little is known about its mechanism of endothelial
      hyperpermeability induction. Here, we demonstrate that in a model of isolated
      perfused rat ileum discontinuation of capillary vascular-endothelial-cadherin (VE
      cadherin) was observed after bolus application of S. aureus alpha-toxin being
      inhibited by the endogenous peptide adrenomedullin (ADM). In vitro, alpha-toxin
      exposure induced loss of immunoreactivity of VE-cadherin and occludin in human
      cultured umbilical vein endothelial cells. Likewise, ADM blocked alpha-toxin
      related junctional protein disappearance from intercellular sites. Additionally,
      cyclic AMP elevation was shown to stabilize endothelial barrier function after
      alpha-toxin application. Although no RhoA activation was noted after endothelial
      alpha-toxin exposure, inhibition of Rho kinase and myosin light chain kinase
      blocked loss of immunoreactivity of VE-cadherin and occludin as well as
      intercellular gap formation. In summary, stabilization of endothelial junctional
      integrity as indicated by interendothelial immunostaining might be an interesting
      approach to stabilize endothelial barrier function in severe S. aureus
      infections.

PMID- 16596366
TI  - Weather impacts on respiratory infections in Athens, Greece.
AB  - In this study the contribution of meteorological parameters to the total
      variability of respiratory infections (RI) is analysed. For this purpose, data on
      the daily numbers of general practitioner (GP) consultations for RI during the
      year 2002 were used. This dataset has been compiled by the Local Health Service
      in the surroundings of Athens, Greece (Acharnes city). The meteorological data
      obtained by the Meteorological Station of the National Observatory of Athens
      comprise daily values of mean, maximum, and minimum air temperature, air
      temperature range, relative humidity, absolute humidity, sunshine, surface
      atmospheric pressure, wind speed, as well as day-to-day changes of these
      parameters. Furthermore, the following biometeorological parameters and thermal
      indices were also evaluated: mean radiant temperature (T (mrt)), predicted mean
      vote (PMV), physiologically equivalent temperature (PET) and standard effective
      temperature (SET*) as well as their day-to-day changes. First, the relationship
      between every meteorological-biometeorological parameter and consultations for RI
      was examined by applying the Pearson Chi-Square Test (chi (2)) to the data of the
      25 compiled contingency tables. In the second stage, the application of
      generalised linear models (GLM) with Poisson distribution to the data revealed
      how much the weather variability leads to statistically important changes in
      consultations for RI. The results of this study contribute to the evidence that
      there is an association between weather conditions and the number of GP
      consultations for RI. More specifically, the influence of air temperature and
      absolute humidity on consultations on the same day is weaker than the lag effect
      ( approximately 2 weeks) related to cold existence and absolute humidity, while a
      strong wind during the preceding 3 days drives a peak in GP consultations.

PMID- 16596368
TI  - Treatment of a biliary-venous fistula following percutaneous biopsy in a
      pediatric living related liver transplant patient.
AB  - Liver biopsy is a common study performed after hepatic transplantation. Most
      centers routinely perform a biopsy 1 week after surgery to evaluate for the
      possibility of acute rejection. Subsequent biopsies are based on clinical
      symptoms and routine hepatic function laboratory testing. We report the clinical
      presentation and treatment of a biliary-venous fistula resulting in sepsis and
      bilhemia (elevated serum bilirubin levels caused by a biliary-venous fistula) in
      a 2(1/2)-year-old patient 4 months after partial left lateral segment living
      related liver transplantation. This case is unusual in that the fistula is the
      reversal of the more common venous-biliary fistula. The fistula developed after a
      percutaneous liver biopsy was performed.

PMID- 16596370
TI  - Abstracts of the International Pediatric Radiology 5th Conjoint Meeting. May 16
      20, 2006. Montreal, Canada.

PMID- 16596369
TI  - Comparison of lingual tonsil size as depicted on MR imaging between children with
      obstructive sleep apnea despite previous tonsillectomy and adenoidectomy and
      normal controls.
AB  - BACKGROUND: Cine MRI has become a useful tool in the evaluation of patients with
      persistent obstructive sleep apnea (OSA) despite previous surgical intervention
      and in patients with underlying conditions that render them susceptible to
      multilevel airway obstruction. Findings on cine MRI studies have also increased
      our understanding of the mechanisms and anatomic causes of OSA in children.
      OBJECTIVE: To compare lingual tonsil size between children with OSA and a group
      of normal controls. In addition, a subanalysis was made of the group of children
      with OSA comparing lingual tonsils between children with and without underlying
      Down syndrome. MATERIALS AND METHODS: Children with persistent OSA despite
      previous palatine tonsillectomy and adenoidectomy and controls without OSA
      underwent MR imaging with sagittal fast spin echo inversion-recovery images, and
      lingual tonsils were categorized as nonperceptible at imaging or present and
      measurable. When present, lingual tonsils were measured in the maximum anterior
      posterior diameter. If lingual tonsils were greater than 10 mm in diameter and
      abutting both the posterior border of the tongue and the posterior pharyngeal
      wall, they were considered markedly enlarged. RESULTS: There were statistically
      significant differences between the OSA and control groups for the presence vs.
      nonvisualization of lingual tonsils (OSA 33% vs. control 0%, P=0.0001) and mean
      diameter of the lingual tonsils (OSA 9.50 mm vs. control 0.0 mm, P=0.00001).
      Within the OSA group, there were statistically significant differences between
      children with and without Down syndrome for the three lingual tonsil width
      categories (P=0.0070) and occurrence of markedly enlarged lingual tonsils (with
      Down syndrome 35% vs. without Down syndrome 3%, P=0.0035). CONCLUSIONS:
      Enlargement of the lingual tonsils is relatively common in children with
      persistent obstructive sleep apnea after palatine tonsillectomy and
      adenoidectomy. This is particularly true in patients with Down syndrome.

PMID- 16596377
TI  - The immune system and cancer: the evolving role of molecular imaging and
      molecular targeted therapy.

PMID- 16596379
TI  - Increased 67gallium uptake among polymyalgia rheumatica patients. Is it
      additional evidence of its vasculitic nature?
AB  - Giant cell arteritis/temporal arteritis (GCA/TA) and polymyalgia rheumatica (PMR)
      are closely related conditions that affect middle age and older patients and
      frequently occur together. Many authorities consider them to be different phases
      of the same disease. A study was undertaken of the possible contribution of
      gallium-67 ((67)Ga) single photon emission tomography (SPECT) scintigraphy to the
      diagnosis of GCA/TA and PMR, and to support the possible hypothesis of vasculitic
      nature of PMR. Nine consecutive patients with PMR, and nine consecutive patients
      with GCA/TA were included in the study. All patients fulfilled the American
      College of Rheumatology criteria for GCA/TA and Healey's criteria for PMR. The
      control patients group consisted of those who underwent (67)Ga scintigraphy for
      febrile illness. All patients and controls underwent (67)Ga SPECT scan of the
      skull on a dual-head Helix gamma camera 2 days after I.V. injection of 8-10 mCi
      of (67)Ga citrate. (67)Ga uptake ratio of temporal bone region to bone out of
      temporal area (TR/Bone) was estimated on transaxial and coronary slices after
      SPECT scan reconstruction. For each patient and control the calculations of both
      temporal areas were done. All GCA/TA and PMR patients showed increased uptake in
      both temporal areas of the skull, while (67)Ga uptake among GCA/TA was the
      highest, 1.31+/-0.14 in tranaxial view and 1.47+/-0.16 in coronary view. (67)Ga
      uptake among PMR patients was lower, 1.19+/-0.11 and 1.28+/-0.13, respectively.
      In comparison, the control patients showed the lowest (67)Ga uptake, 1.04+/-0.09
      in transaxial view and 1.11+/-0.06 in coronary view. The results differ
      significantly between the three groups. It seems that (67)Ga SPECT scan may
      become a useful tool in the investigation of patients with suspicion of GCA/TA
      and PMR. Our findings of the increased (67)Ga uptake in the temporal areas among
      PMR patients add new arguments for vasculitic nature of this disorder.

PMID- 16596378
TI  - Brown fat in breast cancer patients: analysis of serial (18)F-FDG PET/CT scans.
AB  - PURPOSE: It has recently been suggested that FDG accumulation in the brown
      adipose tissue varies as a function of age, sex and outdoor temperature. The aim
      of this study was to assess changes in FDG uptake in brown fat in patients based
      on serial PET/CT scans and to compare our results with previous findings.
      METHODS: Early response to neoadjuvant chemotherapy in 33 female breast cancer
      patients was assessed by FDG PET. Five PET/CT scans were performed for each
      patient. PET/CT images were analysed retrospectively. PET scans were considered
      positive when diffuse, symmetrical, abnormal "USA" (uptake in supraclavicular
      area) fat was detected. RESULTS: A total of 163 PET images were analysed. Seventy
      four PET scans (45%) revealed abnormal FDG uptake in the supraclavicular area.
      These foci were present on uncorrected and attenuation-corrected images. FDG
      uptake was identical on all five scans in only five patients. No significant
      relationship was found between abnormal FDG uptake and outdoor temperature, age
      or time interval between chemotherapy and PET. Abnormal FDG uptake in the neck
      seemed to predominantly occur in patients with a low body mass index (p<0.05).
      Most significant changes in the PET/CT scan results were observed during
      chemotherapy with docetaxel (p<0.05). When observed, bilateral uptake in the neck
      was more intense than background uptake (p<0.00001). CONCLUSION: This study shows
      that FDG uptake in the neck varies as a function of time, that it is unrelated to
      age or outdoor temperature, and that bilateral uptake is generally intense.

PMID- 16596380
TI  - Penetration of beta-naphthylamine and o-toluidine through human skin in vitro.
AB  - Several aromatic amines (AAs) are known to be carcinogens for humans. AAs are
      considered to be substantially absorbed through the skin. However, the database
      for dermal absorption of AAs in general is limited and no specific studies on
      dermal absorption of beta-naphthylamine (BNA) and o-toluidine (OT) have been
      published. In the present study using diffusion cells, we investigated dermal
      penetration of BNA and OT through human skin. We have demonstrated that both AAs
      penetrate through human skin fast (lag time: approximately 1.2 vs. 0.8 h) and in
      high percentages (54 vs. 50%, respectively, of the applied dose within 24 h). A
      skin notation is therefore justified for these substances.

PMID- 16596381
TI  - Unusual aggressive course of a giant cell tumor of soft tissue during
      immunosuppressive therapy.
AB  - Giant cell tumor of soft tissue with low malignant potential (GCT-ST) is a low
      grade, primary soft tissue sarcoma with histological and clinical features
      similar to giant cell tumor of the bone. The main tumor localizations are the
      extremities, but it may also occur in the head and neck region. GCT-ST shows a
      recurrence rate of approximately 15%, but it very rarely metastasizes. The risk
      of cancer development, especially of the skin, is up to fivefold increased in
      immunosuppressed patients after organ transplantation. The association of
      sarcomas and immunosuppressive therapy is best known for Kaposi sarcomas, whereas
      other types of sarcomas are rarely found. We report of a GCT-ST of low malignant
      potential, which developed under long-term immunosuppression in a patient 12
      years after heart transplantation. The tumor presented with an unusual aggressive
      course and metastatic site: the parotid gland. Therefore, we suggest that in
      patients with immunosuppression, even low malignant cancerous lesions should be
      carefully observed, as their local behavior may be aggressive with development of
      metastasis.

PMID- 16596382
TI  - Monoallelic deletion of the p53 gene through chromosomal translocation in a small
      cell osteosarcoma.
AB  - Small cell osteosarcoma is a rare bone tumor of high-grade malignancy that most
      often arises in the metaphysis of long bones in the second decade of life.
      Cytogenetic and molecular genetic findings in small cell osteosarcoma are poorly
      defined. Conventional cytogenetic analysis of a small cell osteosarcoma arising
      in the proximal tibia of a 9-year-old male revealed a diploid chromosomal
      complement with complex structural rearrangements involving chromosomes 6, 16,
      and 17. Immunohistochemical assessment of p53 protein expression revealed nuclear
      p53 immunoreactivity in approximately 15% of the neoplastic cells. Subsequent
      fluorescence in situ hybridization (FISH) analyses confirmed loss of the p53 gene
      locus on the derivative chromosome 17 homolog and were negative for amplification
      of the MDM2, CDK4, c-MYC, HER-2/neu, CCND1, and COPS3 gene loci. To the best of
      our knowledge, this represents the first demonstration of monoallelic deletion of
      p53 in small cell osteosarcoma, suggesting that p53 alterations may play an
      important role in the development of small cell osteosarcoma as well as
      conventional osteosarcoma.

PMID- 16596383
TI  - Multifocal kaposiform haemangioendothelioma.
AB  - Kaposiform haemangioendothelioma (KHE) is a rare, locally aggressive vascular
      spindle cell proliferation, with resemblance to Kaposi's sarcoma. This tumour
      usually occurs in skin and retroperitoneum of infants and young children and is
      often complicated by the Kasabach-Merritt phenomenon (KMP). A 3-year-old boy
      presented with a right submandibular swelling due to lymphadenopathies, a
      violaceous skin lesion at the left commissure of the lips and an ill-defined
      lesion in the right thyroid lobe. There were some signs of KMP. Histological
      examination revealed a typical infiltrative multilobular spindle cell
      proliferation with slit-like vascular spaces in these three localisations.
      Immunohistochemical stains showed positivity for CD34 and CD31 and many alpha
      smooth muscle actin-positive spindle cells around the vascular spaces. There was
      no Herpes virus type 8 expression. The presented case is unique in two ways.
      First, thyroid involvement of KHE has never been described in the literature
      until now. Secondly, and most remarkably, the multifocal presentation in three
      anatomically distinct and separated localisations is extremely unusual.

PMID- 16596384
TI  - Sulfur uptake in the ectomycorrhizal fungus Laccaria bicolor S238N.
AB  - The importance of the ectomycorrhiza symbiosis for plant acquisition of
      phosphorus and nitrogen is well established whereas its contribution to sulfur
      nutrition is only marginally understood. In a first step to investigate the role
      of ectomycorrhiza in plant sulfur nutrition, we characterized sulfate and
      glutathione uptake in Laccaria bicolor. By studying the regulation of sulfate
      uptake in this ectomycorrhizal fungus, we found that in contrast to bacteria,
      yeast, and plants, sulfate uptake in L. bicolor was not feedback-inhibited by
      glutathione. On the other hand, sulfate uptake was increased by sulfur starvation
      as in other organisms. The activity of 3'-phosphoadenosine 5'-phosphosulfate
      reductase, the key enzyme of the assimilatory sulfate reduction pathway in fungi,
      was increased by sulfur starvation and decreased after treatment with glutathione
      revealing an uncoupling of sulfate uptake and reduction in the presence of
      reduced sulfur compounds. These results support the hypothesis that L. bicolor
      increases sulfate supply to the plant by extended sulfate uptake and the plant
      provides the ectomycorrhizal fungus with reduced sulfur.

PMID- 16596387
TI  - [Interactions between itch and pain].
AB  - The discovery of specific pathways for the processing of itch has greatly
      enhanced our understanding of the physiology of pruritus. However, the complex
      interactions between itch and pain are only partly understood. This review
      focuses on the neurophysiological basis of itch under experimental and clinical
      conditions. Chronic inflammatory diseases can locally sensitize nerve endings and
      thereby contribute to itch. In addition, there is increasing evidence that also
      central processing of itch can be sensitized in pruritus patients. Interestingly,
      this pattern of peripheral and central sensitization in pruritus has striking
      similarities to the one observed in chronic pain patients. The presumed
      similarities in underlying sensitizing mechanisms between itch and pain has major
      therapeutic consequences as successful therapies for chronic pain might be used
      also in chronic itch.

PMID- 16596389
TI  - The high-resolution structures of the neutral and the low pH crystals of
      aminopeptidase from Aeromonas proteolytica.
AB  - The aminopeptidase from Aeromonas proteolytica (AAP) contains two zinc ions in
      the active site and catalyzes the degradation of peptides. Herein we report the
      crystal structures of AAP at 0.95-A resolution at neutral pH and at 1.24-A
      resolution at low pH. The combination of these structures allowed the precise
      modeling of atomic positions, the identification of the metal bridging oxygen
      species, and insight into the physical properties of the metal ions. On the basis
      of these structures, a new putative catalytic mechanism is proposed for AAP that
      is likely relevant to all binuclear metalloproteases.

PMID- 16596390
TI  - Analyzing heme proteins using EPR techniques: the heme-pocket structure of ferric
      mouse neuroglobin.
AB  - In this work, an electron paramagnetic resonance (EPR) strategy to study the heme
      pocket structure of low-spin ferric heme proteins is optimized. Frozen solutions
      of ferric mouse neuroglobin (mNgb) are analyzed by means of electron spin echo
      envelope modulation and pulsed electron-nuclear double resonance techniques. The
      hyperfine and nuclear quadrupole couplings of the directly coordinating heme and
      histidine nitrogens are derived and are discussed in comparison with known data
      of other ferric porphyrin compounds. In combination with the hyperfine matrices
      of the imidazole protons, the 14N EPR parameters reveal structural information on
      the heme pocket of mNgb that is in agreement with previous X-ray diffraction data
      on neuroglobins.

PMID- 16596388
TI  - The structure of the 2[4Fe-4S] ferredoxin from Pseudomonas aeruginosa at 1.32-A
      resolution: comparison with other high-resolution structures of ferredoxins and
      contributing structural features to reduction potential values.
AB  - The structure of the 2[4Fe-4S] ferredoxin (PaFd) from Pseudomonas aeruginosa,
      which belongs to the Allochromatium vinosum (Alvin) subfamily, has been
      determined by X-ray crystallography at 1.32-A resolution, which is the highest up
      to now for a member of this subfamily of Fds. The main structural features of
      PaFd are similar to those of AlvinFd. However, the significantly higher
      resolution of the PaFd structure makes possible a reliable comparison with
      available high-resolution structures of [4Fe-4S]-containing Fds, in an effort to
      rationalize the unusual electrochemical properties of Alvin-like Fds. Three major
      factors contributing to the reduction potential values of [4Fe-4S]2+/+ clusters
      of Fds, namely, the surface accessibility of the clusters, the N-H...S hydrogen
      bonding network, and the volume of the cavities hosting the clusters, are
      extensively discussed. The volume of the cavities is introduced in the present
      work for the first time, and can in part explain the very negative potential of
      cluster I of Alvin-like Fds.

PMID- 16596391
TI  - Aberrant profile of gene expression in cloned mouse embryos derived from donor
      cumulus nuclei.
AB  - Somatic cell nuclear transfer has successfully been used to clone several
      mammalian species including the mouse, albeit with extremely low efficiency. This
      study investigated gene expression in cloned mouse embryos derived from cumulus
      cell donor nuclei, in comparison with in vivo fertilized mouse embryos, at
      progressive developmental stages. Enucleation was carried out by the conventional
      puncture method rather than by the piezo-actuated technique, whereas nuclear
      transfer was achieved by direct cumulus nuclear injection. Embryonic development
      was monitored from chemically induced activation on day 0 until the blastocyst
      stage on day 4. Poor developmental competence of cloned embryos was observed,
      which was confirmed by lower cell counts in cloned blastocysts, compared with the
      in vivo fertilized controls. Subsequently, real-time polymerase chain reaction
      was used to analyze and compare embryonic gene expression at the 2-cell, 4-cell,
      and blastocyst stages, between the experimental and control groups. The results
      showed reduced expression of the candidate genes in cloned 2-cell stage embryos,
      as manifested by poor developmental competence, compared with expression in the
      in vivo fertilized controls. Cloned 4-cell embryos and blastocysts, which had
      overcome the developmental block at the 2-cell stage, also showed up-regulated
      and down-regulated expression of several genes, strongly suggesting incomplete
      nuclear reprogramming. We have therefore demonstrated that aberrant embryonic
      gene expression is associated with low developmental competence of cloned mouse
      embryos. To improve the efficiency of somatic cell nuclear transfer, strategies
      to rectify aberrant gene expression in cloned embryos should be investigated.

PMID- 16596393
TI  - Plasticity of interstitial cells of Cajal: a study of mouse colon.
AB  - Ablation of the myenteric plexus in mouse colon with the detergent benzalkonium
      chloride (BAC) is followed by considerable recovery of the nerves, indicating
      that this plexus is capable of regeneration and has plasticity. Interstitial
      cells of Cajal (ICC) are closely associated with enteric nerves, and the
      acquisition and maintenance of their adult phenotype are nerve-dependent. Little
      is known about the regenerative processes of ICC or about the possible dependence
      of these processes on neurons. To address these questions, we ablated the
      myenteric plexus in the mouse colon with BAC and followed changes in the adjacent
      ICC (ICC-MP) from day 2 to day 70 after treatment, by using c-kit
      immunohistochemistry and electron microscopy. In the untreated area, c-kit
      positive cells and ICC-MP with normal ultrastructural features were always
      present. The region partially affected by BAC contained some c-kit-positive
      cells, and either normal or vacuolated ICC-MP were observed by electron
      microscopy. Moreover, at days 60-70, ICC-MP with particularly extended rough
      endoplasmic reticulum were present in this area. In the treated area, either
      denervated or reinnervated, c-kit-positive cells were always absent. By day 14
      after BAC treatment, nerve fibers had started to grow back into the treated
      region and, in the reinnervated area, cells with fibroblast-like features
      appeared and were seen to contact both nerve endings and smooth muscle cells and
      to acquire some typical ICC features. Thus, ICC are vulnerable to external insult
      but appear to have some ability to regenerate.

PMID- 16596392
TI  - Stage-dependency of apoptosis and the blood-testis barrier in the dogfish shark
      (Squalus acanthias): cadmium-induced changes as assessed by vital fluorescence
      techniques.
AB  - Naturally occurring heavy metals and synthetic compounds are potentially harmful
      for testicular function but evidence linking heavy metal exposure to reduced
      semen parameters is inconclusive. Elucidation of the exact stage at which the
      toxicant interferes with spermatogenesis is difficult because the various germ
      cell stages may have different sensitivities to any given toxicant, germ cell
      development is influenced by supporting testicular somatic cells and the presence
      of inter-Sertoli cell tight junctions create a blood-testis barrier, sequestering
      meiotic and postmeiotic germ cells in a special microenvironment. Sharks such as
      Squalus acanthias provide a suitable model for studying aspects of vertebrate
      spermatogenosis because of their unique features: spermatogenesis takes place
      within spermatocysts and relies mainly on Sertoli cells for somatic cell support;
      spermatocysts are linearly arranged in a maturational order across the diameter
      of the elongated testis; spermatocysts containing germ cells at different stages
      of development are topographically separated, resulting in visible zonation in
      testicular cross sections. We have used the vital dye acridine orange and a novel
      fluorescence staining technique to study this model to determine (1) the efficacy
      of these methods in assays of apoptosis and blood-testis barrier function, (2)
      the sensitivity of the various spermatogonial generations in Squalus to cadmium
      (as an illustrative spermatotoxicant) and (3) the way that cadmium might affect
      more mature spermatogenic stages and other physiological processes in the testis.
      Our results show that cadmium targets early spermatogenic stages, where it
      specifically activates a cell death program in susceptible (mature)
      spermatogonial clones, and negatively affects blood-testis barrier function.
      Since other parameters are relatively unaffected by cadmium, the effects of this
      toxicant on apoptosis are presumably process-specific and not attributable to
      general toxicity.

PMID- 16596394
TI  - Histochemical and immunocytochemical study of hard tissue formation in dental
      pulp during the healing process in rat molars after tooth replantation.
AB  - Dental pulp is assumed to possess the capacity to elaborate both bone and dentin
      matrix under the pathological conditions following tooth injury. This study was
      undertaken to clarify the mechanism inducing bone formation in the dental pulp by
      investigating the pulpal healing process, after tooth replantation, by micro
      computed tomography (mu-CT), immunocytochemistry for heat-shock protein (HSP)-25
      and cathepsin K (CK), and histochemistry for both alkaline phosphatase (ALP) and
      tartrate-resistant acid phosphatase (TRAP). Under deep anesthesia, the upper
      right first molar of 4-week-old Wistar rats was extracted and immediately
      repositioned in the original socket. In control teeth at this age, the periphery
      of the coronal dental pulp showed intense ALP-positive and HSP-25-positive
      reactions, whereas there were no TRAP-positive or CK-positive cells. Tooth
      replantation weakened or terminated ALP-positive and HSP-25-positive reactions in
      the pulp tissue at the initial stages. At 3-7 days after operation, the ALP
      positive region recovered from the root apex to the coronal pulp followed by HSP
      25-positive reactions in successful cases showing tertiary dentin formation. In
      other cases, TRAP-positive and CK-positive cells appeared in the pulp tissue of
      the replanted tooth at postoperative days 5-10 and remained associated with the
      bone tissue after 12-60 days. Immunoelectron microscopy clearly demonstrated that
      CK-positive osteoclast-lineage cells made contact with mesenchymal cells with
      prominent nucleoli and well-developed cell organelles. These data suggest that
      the appearance of TRAP-positive and CK-positive cells is involved in the
      induction of bone tissue formation in dental pulp.

PMID- 16596395
TI  - Organ-specific expression of IGF-I during early development of bony fish as
      revealed in the tilapia, Oreochromis niloticus, by in situ hybridization and
      immunohistochemistry: indication for the particular importance of local IGF-I.
AB  - The cellular sites of insulin-like growth factor I (IGF-I) synthesis in the early
      developing tilapia (0-140 days post fertilization, DPF) were investigated. IGF-I
      mRNA and peptide appeared in liver as early as 4 DPF and in gastro-intestinal
      epithelial cells between 5-9 DPF. In exocrine pancreas, the expression of IGF-I
      started at 4 DPF and continued until 90 DPF. IGF-I production was detected in
      islets at 6 DPF in non-insulin cells and occurred throughout life. In renal
      tubules and ducts, IGF-I production started at 8 DPF. IGF-I production in
      chondrocytes had its onset at 4 DPF, was more pronounced in growing regions and
      was also found in adults. IGF-I mRNA and peptide appeared in the cytoplasm of
      skeletal muscle cells at 4 DPF. In gill chloride cells, IGF-I production started
      at 6 DPF. At 13 DPF, IGF-I was detected in cardiac myocytes. IGF-I-producing
      epidermal cells appeared at 5 DPF. In brain and ganglia, IGF-I was expressed in
      virtually all neurones from 6 to 29 DPF, their number decreasing with age.
      Neurosecretory IGF-I-immunoreactive axons were first seen in the neurohypophysis
      around 17 DPF. Endocrine cells of the adenohypophysis exhibited IGF-I mRNA at 28
      DPF and IGF-I immunoreactivity at 40 DPF. Thus, IGF-I appeared early (4-5 DPF),
      first in liver, the main source of endocrine IGF-I, and then in organs involved
      in growth or metabolism. The expression of IGF-I was more pronounced during
      development than in juvenile and adult life. Local IGF-I therefore seems to have
      a high functional impact in early growth, metabolism and organogenesis.

PMID- 16596396
TI  - Cross-species transferability of G. arboreum-derived EST-SSRs in the diploid
      species of Gossypium.
AB  - Diploid species with a common Gossypium origin are highly diverse in morphology
      and have been classified into eight genomic groups designated A-G and K. In this
      study, the transferability of 207 Gossypium arboreum-derived expressed sequence
      tag-simple sequence repeat (EST-SSR) primer pairs was examined among 25 different
      diploid accessions representing 7 genomes and 23 Gossypium species. We found that
      124 of the 207 (60%) primer pairs produced amplification products in all 25
      accessions. The remaining 83 (40%) primer pairs produced amplification in only a
      subset of species, ranging from 13 to 22 species, which is consistent with some
      genome- and species-specific amplification. The cross-species amplification of
      these EST-SSRs in 22 diploid species was 96.5% in 4,554 combinations (207 SSRsx22
      species), indicative of a high transferability among the Gossypium species.
      Furthermore, a high level of polymorphism with an average number of 6.53 alleles
      per SSR marker was detected. No correlation was found between the repeat motif
      type and cross-species amplification. DNA sequencing showed that the high-level
      polymorphism findings was mainly due to changes in the number of repeat motifs
      and that the high transferability can be attributed to a higher-level
      conservation in the flanking regions among these diploid Gossypium species. The
      transferability among these different diploid species presented here can increase
      the efficiency of transferring genetic information across species and further
      enhance their introgression into cultivated cotton species by the molecular
      tagging of important genes existing in these diploid species using the EST-SSR
      markers.

PMID- 16596397
TI  - Cell and tissue responses of a range of Urotensin II analogs at cloned and native
      urotensin II receptors. Evidence for coupling promiscuity.
AB  - Urotensin II (U-II) is the peptide ligand for the G-protein-coupled U-II receptor
      (UT). U-II has been dubbed "the most potent vasoconstrictor identified to date".
      However, in vivo studies with this system are hampered by the paucity of
      available ligands. Here, we characterise Chinese hamster ovary (CHO) cells
      expressing the human UT receptor in the following assays; (1) [(125)I]U-II
      binding, (2) GTPgamma[(35)S] binding, (3) cAMP formation, and (4) intracellular
      Ca(2+). We assess activity of 9 U-II analogues using these paradigms and examine
      their ability to contract isolated rat aorta. CHO(hUT) cells bound [(125)I]U-II
      with a B (max) and K (d) of 1,110+/-70 fmol/mg protein and 742 pM, respectively.
      hU-II stimulated GTPgamma[(35)S] binding (pEC(50) 8.38), optimal at low (0.1 muM)
      GDP concentrations. The hU-II GTPgamma[(35)S] response was partially PTx
      sensitive and there was a potent (pEC(50) 9.23) low efficacy ( approximately 20%
      inhibition) coupling to adenylyl cyclase. In CHO(hUT) cells hU-II stimulates
      calcium release from intracellular stores (pEC(50) 8.80) and calcium influx in a
      PTx-insensitive manner. In our structure-activity relationship study most ligands
      acted as full agonists. However, urantide behaved as a partial agonist (pEC(50)
      7.67/pK(B) 7.55) in GTPgamma[(35)S] binding, a full agonist (pEC(50) 8.11) for
      increases in intracellular Ca(2+) and a competitive antagonist in the rat aorta
      bioassay (pK(B) 8.59). Collectively, these data show promiscuity at high
      expression and indicate the need for careful multi-assay evaluation of novel U-II
      analogues. Further modification of urantide, in order to eliminate residual
      agonist activity and to identify novel ligands for in vivo cardiovascular studies
      are clearly warranted.

PMID- 16596398
TI  - Escalation of i.v. cocaine self-administration and reinstatement of cocaine
      seeking behavior in rats bred for high and low saccharin intake.
AB  - RATIONALE: Rats selectively bred for high saccharin (HiS) intake consume more
      alcohol, acquire intravenous (i.v.) cocaine self-administration more rapidly, and
      show more dysregulated patterns of cocaine self-administration than their low
      saccharin-consuming (LoS) counterparts. OBJECTIVES: The purpose of the present
      study was to determine whether HiS and LoS rats also differ in the escalation,
      maintenance, extinction, and reinstatement of i.v. cocaine self-administration.
      MATERIALS AND METHODS: Two experiments were conducted in separate groups of rats.
      In the first experiment, HiS and LoS female rats were allowed to self-administer
      cocaine [0.4 mg/kg; fixed ratio (FR) 1] under short (ShA, 2 h per day) or long
      (LgA, 12 h per day) access conditions for 21 days. Session lengths were
      subsequently equated (2 h), and FR1-maintained cocaine self-administration was
      examined. In the second experiment, additional groups of HiS and LoS female rats
      were given access to cocaine (0.4 mg/kg; FR 1) self-administration during 2-h
      sessions for 10 days. Subsequently, saline was substituted for cocaine, and
      responding was extinguished. After a 14-day extinction period, saline- and
      cocaine-[5, 10, and 15 mg/kg, intraperitoneal (i.p.)] induced reinstatement of
      drug-seeking behavior was measured. RESULTS: HiS LgA rats escalated their cocaine
      intake more rapidly than LoS rats, and during the 2 h sessions after escalation
      cocaine self-administration was significantly higher in HiS LgA rats, compared to
      LoS LgA rats. HiS rats responded on the cocaine-paired lever more than LoS rats
      during maintenance, extinction, and cocaine-(15 mg/kg) induced reinstatement.
      CONCLUSIONS: These results suggest that HiS and LoS rats have distinct drug
      seeking and drug-taking profiles. The HiS and LoS rats differ along a wide range
      of behavioral dimensions and represent an important model to study the
      interactions of excessive intake of dietary substances and vulnerability to drug
      abuse.

PMID- 16596400
TI  - Cocaine self-administration in rats with histories of cocaine exposure and
      discrimination.
AB  - RATIONALE: Interrelationships between the discriminative stimulus and reinforcing
      properties of psychoactive drugs and the way in which they may interact to
      control drug intake are unclear. Studies have shown that drug history can
      influence the expression of drug-produced behavioral effects. OBJECTIVE: The
      present study examined the acquisition and maintenance of intravenous cocaine
      self-administration in rats with a history of drug discrimination. METHODS: Two
      groups of male hooded rats (n=12 each) were successfully trained in a single
      lever food-reinforced procedure to discriminate cocaine (10 mg/kg) from saline.
      Control groups (n=12 each) received drug injections and/or saline injections only
      and lever-pressed for food reinforcers with no discrimination training.
      Subsequently, all subjects were implanted with chronic jugular catheters and
      allowed to nose-poke for infusions of cocaine (0.2 mg/kg per infusion). RESULTS:
      Initial rates of responding were similar for all groups. Acquisition of self
      administration on a FR-10 schedule of drug delivery was significantly faster for
      cocaine-exposed rats in comparison to all other groups (P<0.02). There were no
      differences between groups in the breaking points of cocaine and saline on a
      progressive ratio schedule of self-administration. Dose-response functions were
      obtained by two methods and were similar for all groups. CONCLUSION: These
      results are consistent with earlier studies demonstrating weakly sensitized
      primary reinforcing properties of cocaine in preexposed rats. Previous learning
      to discriminate cocaine impaired this sensitization.

PMID- 16596399
TI  - Role of 5-HT(1A) receptors in the modulation of stress-induced lactate metabolism
      in the medial prefrontal cortex and basolateral amygdala.
AB  - RATIONALE: Lactate has been shown to play a significant role in energy metabolism
      and reflect neural activity in the brain. OBJECTIVES: Using in vivo microdialysis
      technique, we measured extracellular lactate concentrations in the medial
      prefrontal cortex (mPFC) and the basolateral amygdaloid (BLA) nucleus of rats
      under electric foot shock stress. Moreover, to examine the role of serotonin (5
      HT)(1A) receptors in brain energy metabolism in response to stressors, we
      attempted to determine whether the stress-induced changes of extracellular
      lactate levels in the mPFC and BLA are attenuated by tandospirone, a partial
      agonist at 5-HT(1A) receptors, or perospirone, a novel atypical antipsychotic
      with a 5-HT(1A) receptor partial agonist and 5-HT(2A)/dopamine-D(2) antagonist
      property. RESULTS: Foot shock stress led to an increase in extracellular lactate
      concentrations both in the mPFC and BLA. Tandospirone (2 mg/kg) attenuated the
      foot shock stress-induced increase of extracellular lactate concentrations in
      both of the brain regions, which was blocked by pretreatment with WAY-100635, a
      selective 5-HT(1A) antagonist. On the other hand, perospirone (0.3 mg/kg)
      attenuated the increment of extracellular lactate concentrations in the mPFC and
      BLA, which was unaltered by pretreatment with WAY-100635. CONCLUSIONS: These
      results indicate that the foot shock stress-induced increase in lactate
      metabolism is partly regulated by 5-HT(1A) receptors both in cortical and limbic
      regions.

PMID- 16596401
TI  - Certification of a new selenized yeast reference material (SELM-1) for
      methionine, selenomethinone and total selenium content and its use in an
      intercomparison exercise for quantifying these analytes.
AB  - A new selenized yeast reference material (SELM-1) produced by the Institute for
      National Measurement Standards, National Research Council of Canada (INMS, NRC)
      certified for total selenium (2,059+/-64 mg kg(-1)), methionine (Met, 5,758+/-277
      mg kg(-1)) and selenomethionine (SeMet, 3,431+/-157 mg kg(-1)) content is
      described. The +/-value represents an expanded uncertainty with a coverage factor
      of 2. SeMet and Met amount contents were established following a methanesulfonic
      acid digestion of the yeast using GC-MS and LC-MS quantitation. Isotope dilution
      (ID) calibration was used for both compounds, using 13C-labelled SeMet and Met.
      Total Se was determined after complete microwave acid digestion based on ID ICP
      MS using a 82Se spike or ICP-OES spectrometry using external calibration. An
      international intercomparison exercise was piloted by NRC to assess the state-of
      the-art of measurement of selenomethione in SELM-1. Determination of total Se and
      methionine was also attempted. Seven laboratories submitted results (2 National
      Metrology Institutes (NMIs) and 5 university/government laboratories). For SeMet,
      ten independent mean values were generated. Various acid digestion and enzymatic
      procedures followed by LC ICP-MS, LC AFS or GC-MS quantitation were used. Four
      values were based on species-specific ID calibration, one on non-species-specific
      ID with the remainder using standard addition (SA) or external calibration (EC).
      For total selenium, laboratories employed various acid digestion procedures
      followed by ICP-MS, AFS or GC-MS quantitation. Four laboratories employed ID
      calibration, the remaining used SA or EC. A total of seven independent results
      were submitted. Results for methionine were reported by only three laboratories,
      all of which used various acid digestion protocols combined with determination by
      GC-MS and LC UV. The majority of participants submitted values within the
      certified range for SeMet and total Se, whereas the intercomparison was judged
      unsuccessful for Met because only two external laboratories provided values, both
      of which were outside the certified range.

PMID- 16596403
TI  - Challenges in developing paediatric surgery in Sub-Saharan Africa.
AB  - The aim of the present study is to report on the difficulties in developing
      paediatric surgery in a teaching hospital in Tanzania. The methods are as
      follows: (1) information on the demography and health services of Tanzania were
      obtained from the Ministry of Health and the 1998 consensus report; (2) hospital
      data was obtained from the Medical Director's Office and analysed; (3) the
      current delivery of surgical services for children at the Tumaini University
      Hospital and Kilimanjaro Christian Medical Centre (KCMC) is reported; (4) the
      local, national and international support for the development of surgical
      services for children is noted; (5) the teaching, training and research
      programmes are proposed. The results showed that (1) Tanzania has a population of
      31 million with a total health expenditure of 10%. There is 1 doctor for 23,000
      inhabitants and 1 hospital bed per 940. The infant mortality is 173 per thousand
      life births. (2) The bed capacity at KCMC is 500 with a staff of 40 consultants,
      294 nurses, 246 health attendants and 38 clinical officers. (3) Forty-two percent
      of admissions to the surgical ward and 50% of surgical outpatients are children.
      Surgical newborns are cared for in the special care baby unit and there are no
      neonatal or paediatric ventilators. (4) Support to develop surgical services for
      children has been pledged for locally, nationally and internationally; however,
      delivery of the service has not had the equivalent momentum. (5) The proposed
      teaching and training programme has been approved by the University. There is a
      need for surgical services for children with encouraging support for this
      venture; however, the challenges remain in delivering the service.

PMID- 16596402
TI  - Genetic variation at chemokine receptor CCR5 in leporids: alteration at the 2nd
      extracellular domain by gene conversion with CCR2 in Oryctolagus, but not in
      Sylvilagus and Lepus species.
AB  - Whereas in its natural host (Sylvilagus sps.) the effects of myxoma virus
      infections are benign, in European rabbit (Oryctolagus cuniculus), it causes a
      highly infectious disease with very high mortality rate, known as myxomatosis.
      There is evidence that, as with HIV-1 virus in human, myxoma virus may use
      chemokine receptors such as CCR5 of the host target cell for entry and activation
      of pathways of immune avoidance. We have characterized and compared CCR5 genes of
      leporid species with different susceptibility levels to myxomatosis. The CCR5
      protein of O. cuniculus differs markedly from all those known from other species.
      The most striking was the replacement of a specific peptide motif of the second
      extracellular loop (ECL2) by a motif, which in other species characterizes the
      CCR2 molecules. While absent in Sylvilagus and Lepus species, this CCR2 imposed
      CCR5-ECL2 alteration was observed in all genomes of 25 European rabbits,
      representing the subspecies O. cuniculus algirus and O. cuniculus cuniculus.
      Allelic variation at the rabbit CCR5 locus confirmed that the gene conversion
      predates the subspecies split (1-2 Ma).

PMID- 16596404
TI  - The effect of single and repeated UVB radiation on rabbit cornea.
AB  - BACKGROUND: Cumulative effect of ultraviolet radiation (UVR) is an important
      aspect of UV corneal damage. The purpose of this study was to apply high
      resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS 1H NMR)
      spectroscopy to evaluate the effect of single and repeated UV radiation exposure
      of the same overall dose on the rabbit cornea. METHODS: Corneal surfaces of 24
      normal rabbit eyes were examined for the effects of UVB exposure (312 nm). In the
      first group (UVB1), animals were irradiated with a single dose (3.12 J/cm2; 21
      min) of UVB radiation. The animals in the second group (UVB2) were irradiated
      three times for 7 min every other day (dose of 1.04 J/cm2; days 1, 3, 5) to give
      the same overall dose (3.12 J/cm2). The third group served as an untreated
      control group. One day after the last irradiation, the animals were sacrificed,
      and the corneas were removed and frozen. HR-MAS 1H NMR spectra from intact
      corneas were obtained. Special grouping patterns among the tissue samples and the
      relative percentage changes in particular metabolite concentrations were
      evaluated using modern statistical methods (multivariate analysis, one-way
      ANOVA). RESULTS: The metabolic profile of both groups of UVB-irradiated samples
      was significantly different from the control corneas. Substantial decreases in
      taurine, hypo-taurine and choline-derivatives concentrations and substantial
      elevation in glucose and betaine levels were observed following the UVR exposure.
      There was no significant difference between the effect of a single and repeated
      UVB irradiation of the same overall dose. CONCLUSIONS: For the first time, the
      effects of single and repeated UVR doses on the metabolic profile of the rabbit
      cornea were analysed and compared. The combination of HR-MAS 1H NMR spectroscopy
      and modern statistical methods (multivariate analysis, one-way ANOVA) proved
      suitable to assess the overall view of the metabolic alterations in the rabbit
      corneal tissue following UVB radiation exposure.

PMID- 16596405
TI  - Three-dimensional optical coherence tomographic findings in central serous
      chorioretinopathy.
AB  - PURPOSE: The purpose of this study was to evaluate three-dimensional optical
      coherence tomographic findings at the leakage point on fluorescein angiography in
      central serous chorioretinopathy (CSC) with OCT-ophthalmoscope. METHODS: Twenty
      seven eyes of 26 patients (23 men, three women; mean age, 50 years; range, 30-72)
      diagnosed with CSC were examined with OCT-ophthalmoscope, and transverse and
      longitudinal images were compared with fundus and fluorescein angiography
      findings. RESULTS: Transverse images (C-scan) clearly showed serous retinal
      detachment in all eyes and irregular lesions in retinal pigment epithelium (RPE)
      in 26 of 27 eyes (96%). These results agreed with the location of lesions in
      areas of fluorescein dye leakage on fluorescein angiography. Longitudinal images
      (B-scan) of irregular RPE lesions in transverse images showed RPE detachment
      (PED) in 17 eyes (63%), small protrusion of the RPE layer in five eyes (19%), and
      rough RPE layer in four eyes (15%). CONCLUSIONS: OCT-ophthalmoscope detects
      morphologic changes easily and noninvasively at the point of dye leakage in eyes
      with CSC.

PMID- 16596406
TI  - Outflow mechanisms after deep sclerectomy with two different designs of collagen
      implant in an animal model.
AB  - BACKGROUND: To study experimentally two different shapes of collagen implants
      (CI) used in deep sclerectomy (DS). The ability to promote drainage vessels,
      outflow mechanisms, success rates, and biodegradability, were studied
      prospectively in an animal model. MATERIALS AND METHODS: DS was performed in 20
      eyes of ten rabbits. Each rabbit randomly received a cylindrical CI in one eye,
      while the other eye received a flat CI. Intraocular pressure (IOP) measurement,
      ultrasound biomicroscopy (UBM) examination of DS site and simultaneous
      fluorescein and indocyanin green anterior-segment angiography were performed
      preoperatively, at 1 and 2 weeks, 1, 2, 3, 6 and 9 months for each eye. At the
      end of the follow-up period, outflow facility (OF) was measured and histological
      examinations of the filtration site were performed. RESULTS: In the cylindrical
      implant group, IOP significantly dropped from a mean pre-operative value of
      14.8+/-2.2 mmHg to a mean postoperative values of 10.9+/-3.3, 12.5+/-2.2, 11.8+/
      2.6, 11.2+/-2.3, 10.7+/-1.9, 14.0+/- 3.2, 12.6+/-2.4 mmHg at 1, 2 weeks, and 1,
      2, 3, 6, and 9 months, respectively. In the flat CI group, IOP significantly
      dropped from a mean preoperative value of 14.1+/-1.8 mmHg to a mean postoperative
      values of 10.4+/-2.7, 12.7+/-1.9, 12.5+/-3.2, 11.2+/-1.6, 11.6+/-1.8, 11.5+/-2.3,
      11.0+/-2.2 mmHg at 1, 2 weeks, and at 1, 2, 3, 6, and 9 months, respectively. UBM
      images showed a gradual resorption of both type of CI during the first 3 months,
      and angiographies showed progressive growth of drainage vessels around the
      filtration site in both groups. The mean OF 9 months postoperatively for the
      cylindrical CI was 0.53 (SD +/- 0.23) ml/ min per mmHg and was 0.56 (SD+/-0.17)
      ml/min per mmHg for the flat CI (P=0.6). Histological examination revealed
      excellent biocompatibilty and a high density of drainage vessels in the sclera
      around the operative site in both groups. CONCLUSION: Using IOP and OF
      measurements, UBM, angiography, and histology, we were able to compare two types
      of CI used as space maintainer in DS. Both CIs showed efficient IOP lowering
      effect and outflow facility increase, possibly explained by stimulation of
      drainage vessels growth. Both implants showed excellent biocompatibility. The
      flat CI showed a slight tendency towards better overall performances.

PMID- 16596407
TI  - In-patient management and treatment satisfaction after intravitreous plasminogen
      activator injection.
AB  - AIMS: To assess patient satisfaction after intravitreous plasminogen activator
      injections for subretinal hemorrhages secondary to age-related macular
      degeneration (AMD) and to analyse how it relates to the patients' postoperative
      visual and functional abilities. Further, to suggest ways to improve in-patient
      management and thereby treatment satisfaction. METHODS: A consecutive series of
      101 patients with a subretinal hemorrhage of at least one disk diameter were
      enrolled in this longitudinal prospective study conducted during 2001-2004. After
      complete preoperative eye examination all patients were treated with intravitreal
      injection of 25 microg recombinant tissue plasminogen activator (rTPA) and 0.5 ml
      sulphur hexafluoride gas (SF6), followed by face-down positioning for 1 week.
      Patient satisfaction was assessed using standardised questionnaires administered
      postoperatively at 4 and 12 months. Outcome measures were: (1) responses to the
      patient satisfaction survey, (2) degree of satisfaction with in-patient
      management, (3) subjective change in the patients' functional status, and (4)
      visual acuity results. RESULTS: Whereas the patients' actual functional status
      deteriorated from a median value of 2.4 at 4 months to 3.4 at 12 months, their
      recall of their preoperative functional status shifted from a median value of 4.2
      to to 2.3, consecutively. Twelve months after treatment, 75% of patients reported
      an improved visual acuity, however, only 12% reported satisfaction with
      treatment. 67.4-87% of patients were dissatisfied with various areas of in
      patient management. CONCLUSIONS: Satisfaction with plasminogen activator
      injection treatment is low even though patients experience an improved visual and
      functional status at 12 months. This suggests that the current system requires
      improvement in certain areas such as in-patient management.

PMID- 16596408
TI  - A novel method for patch-clamp automation.
AB  - An increasing demand of the pharmaceutical industry for automated
      electrophysiological stations for ion channel drug discovery has recently
      resulted in the development of several commercial platforms for secondary and
      safety screening of ion channel modulators. These commercial systems have
      demonstrated an enhanced throughput, however, often at the expense of some
      quality-sensitive aspects of traditional patch-clamp recordings. To improve data
      quality and content, we have developed a patch-clamp robot that fully automates
      manual patch-clamp recordings, including patch pipette handling, gigaseal
      formation, obtaining whole-cell or perforated-cell configuration, drug
      application, and data acquisition. Utilization of glass micropipettes results in
      high-quality electrophysiological recordings with an overall success rate of
      about 30% in perforated-cell mode. A fast drug application system with low volume
      requirements (1-1.5 ml) allows the study of ligand-gated ion channels on a
      millisecond scale. As proof-of-concept, we present two assays developed for
      voltage-gated human ether-a-go-go-related and ligand-gated alpha(7) nicotinic
      receptor ion channels. The system throughput was a single concentration-response
      curve every 30-40 min or 12-17 6-point concentration-response curves daily,
      representing a significant improvement of typical manual patch-clamp throughput.
      This system represents an efficient method for patch-clamp automation without the
      need for a complex and expensive electrophysiological set-up for cell
      visualization.

PMID- 16596409
TI  - Spent growth medium of Pantoea agglomerans primes wheat suspension cells for
      augmented accumulation of hydrogen peroxide and enhanced peroxidase activity upon
      elicitation.
AB  - Induced disease resistance in plants is based on multiple mechanisms, including
      cell "priming", i.e. an enhancement of the capacity to mobilize cellular defense
      responses upon pathogen attack. Potent inducers of priming are, for example,
      salicylic acid, synthetic compounds such as a benzothiadiazole, and certain
      rhizosphere bacteria. While priming is well characterized for a number of dicot
      plants, only few cases of priming are documented in monocots. Here, we report
      that the spent growth medium of the Gram negative bacterium Pantoea agglomerans
      is capable of priming wheat cells (Triticum aestivum L. cv Prelude-Sr5) for
      elicitor-induced defense responses. Pre-incubation of suspension-cultured wheat
      cells with growth medium of P. agglomerans led to a strong enhancement of an
      oxidative burst that has been induced by chitin or chitosan and to an increase in
      extracellular peroxidase activity. Moreover, exopolysaccharides (EPS) were
      isolated from the spent growth medium and demonstrated to be sufficient for the
      induction of H2O2 priming. The EPS-induced priming was shown to be time- and
      concentration-dependent. We conclude that EPS are the or one of several priming
      active component(s) in the spent growth medium of P. agglomerans. The present
      work is the first report of priming in a monocot plant by a specific component of
      bacterial origin. A comparison with known chemical inducers of resistance
      revealed that a benzothiadiazole was able to enhance the oxidative burst similar
      to the spent growth medium or the EPS of P. agglomerans, while salicylic acid was
      not.

PMID- 16596410
TI  - Cellular and organ level localization of maltose in maltose-excess Arabidopsis
      mutants.
AB  - Maltose is the predominant form of carbon exported from the chloroplast at night.
      Plants that lack either the chloroplast maltose transporter or disproportionating
      enzyme 2 (DPE2, EC 2.4.1.25) have excess maltose in leaves. We confirmed that
      DPE2 is not associated with the chloroplast in Arabidopsis thaliana. Using non
      aqueous fractionation methods, we found that essentially all the maltose in mex1
      1 leaves is located inside chloroplasts but only 40% of maltose in dpe2-1 leaves
      is located inside chloroplasts. We found that maltose exists in a significant
      amount in the exudates collected from maltose-accumulating dpe2-1 Arabidopsis
      petioles. However, the amount of maltose in the exudates from mex1-1 petioles was
      not significantly different from that in wild-type phloem exudates. We found
      twice as much maltose in the roots of dpe2-1 plants relative to wild type but the
      maltose level in the roots of mex1-1 plants was not higher than wild type. We
      conclude that maltose accumulated in the cytosol of leaves can be carried from
      the shoots to the roots and that maltose accumulated in the chloroplast of mex1-1
      leaves is not mobilized. By measuring the transcript levels and enzymatic
      activities, we show that maltose-metabolizing enzymes are active in wild-type
      roots. The amount of maltose moved from the shoots to the roots increased in dpe2
      1 plants. The roots of dpe2-1 plants must have the capacity to metabolize the
      excess maltose.

PMID- 16596411
TI  - The conserved arbuscular mycorrhiza-specific transcription of the secretory
      lectin MtLec5 is mediated by a short upstream sequence containing specific
      protein binding sites.
AB  - In Medicago truncatula a family of mycorrhiza-specific expressed lectins has been
      identified recently, but the function and regulation of these lectins during the
      arbuscular mycorrhiza symbiosis are still unknown. In order to characterize a
      first member of this protein family, MtLec5 was analyzed concerning its
      localization and regulation. Confocal laser scanning microscopy showed that
      MtLec5 is a secretory protein indicating a role as a vegetative storage protein,
      which is specifically expressed in mycorrhizal root systems. To study the
      molecular mechanisms leading to the mycorrhiza-specific transcription, deletion
      studies of pMtLec5 were done using reporter gene fusions. Potential cis-acting
      elements could be narrowed down to a 150 bp fragment that was located
      approximately at -300/-150 according to the transcription start, suggesting the
      binding of positive regulators to this area. Similar expression pattern of the
      reporter gene was found after transforming roots of the non-legume Nicotiana
      tabacum with the heterologous promoter-reporter fusions. This indicated that the
      observed mycorrhiza-specific transcriptional induction is not legume-specific.
      Electrophoretic mobility shift assays showed that several factors which were
      exclusively present in mycorrhizal roots bind within the 150 bp promoter area.
      This strengthens the hypothesis of positive regulators mediating the AM-specific
      gene expression.

PMID- 16596412
TI  - Posttranslational regulation of pyruvate, orthophosphate dikinase in developing
      rice (Oryza sativa) seeds.
AB  - Pyruvate, orthophosphate dikinase (PPDK; E.C.2.7.9.1) is most well known as a
      photosynthetic enzyme in C4 plants. The enzyme is also ubiquitous in C3 plant
      tissues, although a precise non-photosynthetic C3 function(s) is yet to be
      validated, owing largely to its low abundance in most C3 organs. The single C3
      organ type where PPDK is in high abundance, and, therefore, where its function is
      most amenable to elucidation, are the developing seeds of graminaceous cereals.
      In this report, we suggest a non-photosynthetic function for C3 PPDK by
      characterizing its abundance and posttranslational regulation in developing Oryza
      sativa (rice) seeds. Using primarily an immunoblot-based approach, we show that
      PPDK is a massively expressed protein during the early syncitial-endosperm/
      cellularization stage of seed development. As seed development progresses from
      this early stage, the enzyme undergoes a rapid, posttranslational down-regulation
      in activity and amount via regulatory threonyl-phosphorylation (PPDK
      inactivation) and protein degradation. Immunoblot analysis of separated seed
      tissue fractions (pericarp, embryo + aleurone, seed embryo) revealed that
      regulatory phosphorylation of PPDK occurs in the non-green seed embryo and green
      outer pericarp layer, but not in the endosperm + aleurone layer. The modestly
      abundant pool of inactive PPDK (phosphorylated + dephosphorylated) that was found
      to persist in mature rice seeds was shown to remain largely unchanged (inactive)
      upon seed germination, suggesting that PPDK in rice seeds function in
      developmental rather than in post-developmental processes. These and related
      observations lead us to postulate a putative function for the enzyme that aligns
      its PEP to pyruvate-forming reaction with biosynthetic processes that are
      specific to early cereal seed development.

PMID- 16596413
TI  - Live cell imaging of phagosome maturation in Staphylococcus aureus infected human
      endothelial cells: small colony variants are able to survive in lysosomes.
AB  - Small colony variants (SCVs) of Staphylococcus aureus have been proposed to
      persist within vascular endothelium, thereby sustaining chronic infections. To
      identify the intracellular SCV location we infected primary human endothelial
      cells with various wild type and SCV strains of S. aureus and visualised
      maturation of phagosomes using live cell imaging. Staphylococci-containing
      phagosomes were matured by sequential and dynamic interactions with Rab5- and
      Rab7-positive vesicles. Within 45-60 min all internalised staphylococci
      accumulated in LAMP-1- and LysoTracker-enriched lysosomal organelles and remained
      there for up to 5 days. Recovery of most staphyloccocal strains was below 1%
      after a 24 h intracellular stay, indicating a high bactericidal activity of the
      endothelial cell lysosomes. However, the menadione auxotroph SCV strain JB1
      displayed a recovery rate of 4% and, furthermore, through multiple intracellular
      passaging a subtype (JB1-P4) with a recovery rate of 25-30% could be generated.
      Interestingly, both JB1 and JB1-P4 also resided exclusively in lysosomes. Thus,
      on one hand we document effective bactericidal activity of human endothelial cell
      lysosomes towards staphylococci, and on the other hand we provide evidence that
      certain SCVs are capable to withstand this activity.

PMID- 16596414
TI  - Infestation of Lymnaea stagnalis by digenean flukes in the Jeziorak Lake.
AB  - The low number of articles on naturally trematode-infected snails results from
      the difficulty to obtain the quantitatively representative material. The main aim
      of our study was to check which age (size) groups of snails are the most
      susceptible to trematode invasion. Furthermore, we examined in which season the
      parasite prevalence is the highest. We collected Lymnaea stagnalis individuals in
      a nearshore zone of the Jeziorak Lake (the longest Polish lake located in
      northern Poland). The shell height of the snails was measured and the infestation
      by trematode larvae was determined. The logistic regression has shown that
      parasite prevalence increased significantly with the snail size (with the
      individuals >30 mm being the most infected), the distance from the beginning of
      the year (i.e., month) and the vicinity of summer.

PMID- 16596416
TI  - Three new species of coccidia (Apicomplexa: Eimeriorina) from the Marble-throated
      skink, Marmorosphax tricolor Bavay, 1869 (Reptilia: Scincidae), endemic to New
      Caledonia with a taxonomic revision of Eimeria spp. from scincid hosts.
AB  - Three new species of coccidia are described from Marble-throated skink
      Marmorosphax tricolor from New Caledonia, namely, Isospora bocagei sp. n.,
      Acroeimeria rouxi sp. n., and Choleoeimeria sadlieri sp.n. All species differ
      markedly from other eimerian coccidia described from scincid hosts. Isospora
      marmorosphaxi develops extra-nuclearly in small intestine. A. rouxi develops
      epicitoplasmatically in small intestine. C. sadlieri affects the gall bladder
      mucosa. Generic affiliation of Eimeria-like coccidia from reptiles is discussed
      and all taxa (with adequate information on endogenous development available) from
      scincid hosts are revised and placed into genera Acroeimeria and Choleoeimeria.

PMID- 16596415
TI  - Oxyrane derivative of alpha-lapachone is potent growth inhibitor of Trypanosoma
      cruzi epimastigote forms.
AB  - The investigation of trypanocidal effects against Trypanosoma cruzi and
      cytotoxicity in VERO cell line of several oxyranes structurally related to beta
      lapachone, nor-beta-lapachone, alpha-lapachone, and 4-methoxy-1,2-naphthoquinone
      is described. It was found that the oxyranes 10 derived from alpha-lapachone
      showed an approximately the same trypanocidal activity of beta-lapachone. In
      addition, all the oxyranes showed less cytotoxicity than the corresponding
      naphthoquinones.

PMID- 16596417
TI  - Beta 2-adrenergic receptor polymorphisms: pharmacogenetic response to
      bronchodilator among African American asthmatics.
AB  - Beta2-adrenergic receptor (beta2AR) gene polymorphisms have been reported to be
      associated with various asthma-related traits in different racial/ethnic
      populations. However, it is unknown whether beta2AR genetic variants are
      associated with asthma in African Americans. In this study, we have examined
      whether there is association between beta2AR genetic variants and asthma in
      African Americans. We have recruited 264 African American asthmatic subjects and
      176 matched healthy controls participating in the Study of African Americans,
      Asthma, Genes and Environments (SAGE). We genotyped seven known and recently
      identified beta2AR SNP variants, then tested genotype and haplotype association
      of asthma-related traits with the beta2AR SNPs in our African American cohort
      with adjustment of confounding effect due to admixture background and
      environmental risk factors. We found a significant association of the SNP -47
      (Arg-19Cys) polymorphism with DeltaFEF(25-75), a measure of bronchodilator drug
      responsiveness, in African American asthmatics after correction for multiple
      testing (P = 0.001). We did not observe association of the SNP +46 (Arg16Gly)
      variant with asthma disease diagnosis and asthma-related phenotypes. In contrast
      to previous results between the Arg16Gly variant and traits related to
      bronchodilator responsiveness, our results indicate that the Arg-19Cys
      polymorphism in beta upstream peptide may play an important role in
      bronchodilator drug responsiveness in African American subjects. Our findings
      highlight the importance of investigating genetic risk factors for asthma in
      different populations.

PMID- 16596418
TI  - Implantation of central venous ports with catheter insertion via the right
      internal jugular vein in oncology patients: single center experience.
AB  - AIM OF WORK: Evaluation of suitability and safety of venous port implantation
      with catheter insertion via the right internal jugular vein in oncology patients.
      PATIENTS AND METHODS: One hundred one totally implantable venous ports were
      placed in 100 patients with malignancies from January 1, 2003 until March 31,
      2005. Catheter of venous port was preferably inserted via the right internal
      jugular vein. We recorded a number of successful implantations using this venous
      approach and the rate of complications during the procedure and follow-up. MAIN
      RESULTS: Ninety-seven catheters (96%) of totally implantable venous ports were
      inserted via the right internal jugular vein in 96 patients, and only in four
      cases were we not able to access this vein. We had no complications related to
      catheter insertion via the right internal jugular vein. Follow-up was made in all
      96 patients with a total access days of 41 in 151 days (mean: 407 days).
      Premature catheter removal was required in six (6.2%, 0.144 per 1,000 access
      days) due to complications: three catheter dislocations/malfunctions (3.1%, 0.072
      per 1,000 access days), one port-related sepsis, one pocket port infection, and
      one decubitus over port (1%, 0.024 per 1,000 access days). Six venous ports were
      removed after completion of the treatment at the patient's request. CONCLUSION:
      The placement of totally implantable venous ports with catheter insertion via the
      right internal jugular vein has a high success rate without any early
      complications. Follow-up also demonstrates a low incidence of late complications
      requiring port removal.

PMID- 16596420
TI  - Intra and inter-observer reliability of determining degree of pelvic incidence in
      high-grade spondylolisthesis using a computer assisted method.
AB  - Pelvic incidence was described as a fundamental parameter to describe spino
      pelvic balance. In high-grade spondylolisthesis, severe dystrophic changes of the
      upper sacral endplate may be responsible for technical difficulties in pelvic
      incidence measurement. We propose to evaluate the reliability of PI measurement
      in high-grade spondylolisthesis patients and to compare the manual method with a
      computer-assisted method. In 30 high-grade spondylolisthesis patients, pelvic
      incidence was measured by manual and computer-assisted technique by the Spineview
      software package. We statistically assessed agreement between the manual and the
      computer-assisted technique, the intra-observer and the inter-observer
      reliability of the computer-assisted technique. Significant correlation was found
      (Spearman's rank R = 0.921 with P<0.001) between manual and computer-assisted
      results. The paired t test (t = 0.979 with P<0.001) and the intraclass
      correlation coefficient (ICC) were also significant. Intra- and inter-observer
      reliability of the computer-assisted technique were excellent with Spearman's
      rank correlation from 0.964 to 0.985 with P<0.001, a paired t test from 0.978 to
      0.983 with P<0.001) and an ICC from 0.986 to 0.992. Intra- and inter-observer
      repeatability were better with the computer-assisted method than with the manual
      technique. We proved the reliability and repetability of a computer-assisted
      angular measurement method in high-grade spondylolisthesis patients. This
      validated measurement technique could be now used to measure the main parameters
      of the sagittal balance of the spine in further studies on spondylolisthesis
      patients.

PMID- 16596419
TI  - Anastrozole is cost-effective vs tamoxifen as initial adjuvant therapy in early
      breast cancer: Canadian perspectives on the ATAC completed-treatment analysis.
AB  - GOALS OF WORK: To conduct an economic analysis comparing tamoxifen and
      anastrozole (Arimidex) in the adjuvant treatment of hormone receptor-positive
      (HR+), post-menopausal early breast cancer patients. MATERIALS AND METHODS: An
      economic model examined typical patients (64 years of age, HR+, 64% node
      negative) from the Arimidex, tamoxifen alone, or in combination (ATAC) trial over
      a lifetime horizon. Rates of events were derived from ATAC trial results. Post
      trial event rates were drawn from the literature for tamoxifen; event rates for
      anastrozole were modified by the relative risks observed in the ATAC trial.
      Resource utilization was drawn from Statistics Canada's Population Health Model
      for breast cancer, supplemented by an expert panel. A public health care system
      perspective, 2004 Canadian prices and a 5% discount rate were employed. RESULTS:
      Anastrozole-taking patients incurred additional hormonal treatment costs compared
      to tamoxifen-taking patients (incremental lifetime cost, 6,974 Canadian dollars
      per patient), partially offset by reduced downstream recurrences of breast cancer
      (1,143 Canadian dollars lifetime savings per patient) for a net incremental cost
      of 5,796 Canadian dollars per patient on anastrozole. The anastrozole-treated
      patients were projected to experience a 5.6% absolute risk reduction of first
      breast cancer recurrence and a 2.8% absolute risk reduction in breast cancer
      death. This corresponded to 30,000 Canadian dollars per life year gained and
      28,000 Canadian dollars per quality-adjusted life year gained (95% confidence
      interval, 17,428 to 54,605 Canadian dollars). The results were affected by the
      duration and extent of anastrozole benefit under sensitivity analysis but
      remained cost-effective. CONCLUSION: Compared to tamoxifen, anastrozole therapy
      is effective and cost-effective as initial adjuvant therapy in post-menopausal,
      HR+ early breast cancer patients.

PMID- 16596422
TI  - Excitability changes in human hand motor area induced by voluntary teeth
      clenching are dependent on muscle properties.
AB  - To investigate whether the early effects of voluntary teeth clenching (VTC) among
      the first dorsal interosseous (FDI), abductor digiti minimi (ADM), and abductor
      pollicis brevis (APB) muscles are differently modulated depending on their muscle
      properties, we examined the responses of motor evoked potentials (MEPs) elicited
      by transcranial magnetic stimulation with selected current directions and by
      brainstem magnetic stimulation (BMS). Although MEP responses with anterior
      medially current direction (preferentially elicited I1-waves) were facilitated in
      all three muscles, those responses with posterior-laterally current direction
      (preferentially elicited I3-waves) were different among FDI, ADM, and APB
      muscles. That is, MEP responses in FDI and APB muscles were significantly
      reduced, whereas those responses in ADM muscle were not significantly reduced.
      Further, inhibitory effects of VTC in FDI muscle were more potent than those in
      ADM or APB muscles. On the other hand, the responses to BMS were unchanged by VTC
      in all three muscles, suggesting that the modulations of MEP were attributed to
      the cortical origin. On the basis of our previous findings that the inhibitory
      connections in FDI muscle are more potent than those in ADM muscle (Takahashi et
      al. in Clin Neurophysiol 116:2757-2764, 2005), the cortical effects of VTC among
      three hand muscles are differently modulated, depending on muscle properties,
      presumably the extents of inhibitory connections to corticospinal tract neurons.
      Considering that the functional capacity in FDI muscle is higher than that in ADM
      or APB muscles, the cortical inhibitory effect of VTC might contribute to the
      sophisticated regulation of the motor outputs even during VTC.

PMID- 16596423
TI  - Pituitary prolactinoma with T cell rich inflammatory infiltrate: a possible
      example of antitumoral immune response to be differentiated from lymphocytic
      hypophysitis.

PMID- 16596425
TI  - Lack of evidence of neuropathology in the locus coeruleus in autism.

PMID- 16596424
TI  - Increased expression of podoplanin in malignant astrocytic tumors as a novel
      molecular marker of malignant progression.
AB  - Podoplanin (aggrus) is a mucin-like transmembrane sialoglycoprotein that is
      expressed on lymphatic endothelial cells. Podoplanin is putatively involved in
      cancer cell migration, invasion, metastasis, and malignant progression and may be
      involved in platelet aggregation. Previously, we showed upregulated expression of
      podoplanin in central nervous system (CNS) germinomas, but not in non
      germinomatous germ cell tumors, except for parts of immature teratomas in limited
      numbers. However, little information exists about its role in CNS astrocytic
      tumors. In this study, 188 astrocytic tumors (30 diffuse astrocytomas, 43
      anaplastic astrocytomas, and 115 glioblastomas) were investigated using
      immunohistochemistry with an anti-podoplanin antibody, YM-1. In 11 of 43
      anaplastic astrocytomas (25.6%) and in 54 of 115 glioblastomas (47.0%),
      podoplanin was expressed on the surface of anaplastic astrocytoma cells and
      glioblastoma cells, especially around necrotic areas and proliferating
      endothelial cells. However, the surrounding brain parenchyma was not stained by
      YM-1. On the other hand, podoplanin expression was not observed in diffuse
      astrocytoma (0/30: 0%). Furthermore, we investigated the expression of podoplanin
      using quantitative real-time PCR and Western blot analysis in 54 frozen
      astrocytic tumors (6 diffuse astrocytomas, 14 anaplastic astrocytomas, and 34
      glioblastomas). Podoplanin mRNA and protein expression were markedly higher in
      glioblastomas than in anaplastic astrocytomas. These data suggest that podoplanin
      expression might be associated with malignancy of astrocytic tumors.

PMID- 16596426
TI  - Heterogeneity of cancer risk due to stochastic effects: emphasis on radiation
      induced effects.
AB  - Persons with exactly the same genetic background, behavior and environment may
      differ in radiation cancer risk, due to the stochastic nature of cancer
      development. These differences are estimated quantitatively by means of the two
      stage clonal expansion model, in which the number of intermediate cells on their
      way to malignancy varies stochastically between individuals. For liver cancer
      after injection of Thorotrast, the estimated relative risk for persons without
      intermediate cells at age 40 is a factor of more than 10 larger than that for
      persons with a large number of intermediate cells. The population-based estimate
      of the relative risk represents an underestimation for most persons at most ages,
      because for persons showing a large number of intermediate cells liver cancer is
      not a rare disease.

PMID- 16596427
TI  - [Psychotherapy in the life sciences].
AB  - In the 150 years since psychotherapies were theoretically founded and first
      practised, changes have occurred in the understanding of humans from concepts
      based on physical sciences to concepts rooted in biologic life sciences.
      Biopsychosocial knowledge of the way human nature links with environmental
      factors has resulted in new views on the causes of psychological disorders and
      the tasks of psychotherapy. The main selective processes of adjustment to the
      environment take place with genetic variations between the 6th and 20th years of
      life and in further developments until death. Psychotherapy has to overcome
      pathologically distorted impressions of the environment. Latent abilities and
      neglected options need to manifest themselves for patients to find a new outlook
      on life.

PMID- 16596429
TI  - Efficient production of Agrobacterium rhizogenes-transformed roots and composite
      plants for studying gene expression in coffee roots.
AB  - The possibility of rapid validation and functional analysis of nematode
      resistance genes is a common objective for numerous species and particularly for
      woody species. In this aim, we developed an Agrobacterium rhizogenes-mediated
      transformation protocol for Coffea arabica enabling efficient and rapid
      regeneration of transformed roots from the hypocotyls of germinated zygotic
      embryos, and the subsequent production of composite plants. The A. rhizogenes
      strain A4RS proved to be the most virulent. High transformation efficiencies
      (70%) were obtained using a 2-week co-cultivation period at a temperature of 15
      18 degrees C. Using a p35S-gusA-int construct inserted in the pBIN19 binary
      plasmid, we could estimate that 35% of transformed roots were GUS positive (co
      transformed). Using the GUS assay as visual marker, 40% composite plants bearing
      a branched co-transformed rootstock could be obtained after only 12 weeks without
      selection with herbicides or antibiotics. Transgenic coffee roots obtained with
      A. rhizogenes did not exhibit the 'hairy' disturbed phenotype and were
      morphologically similar to normal roots. PCR analyses demonstrated that all co
      transformed roots were positive for the expected rolB and gusA genes. Transformed
      and non-transformed root systems from both susceptible and resistant varieties
      were inoculated with Meloidogyne exigua nematode individuals. Inoculation of
      composite plants from the Caturra susceptible variety resulted in the normal
      development of nematode larvae. Numbers of extracted nematodes demonstrated that
      transformed roots retain the resistance/sensibility phenotype of varieties from
      which they are derived. These results suggest that composite plants constitute a
      powerful tool for studying nematode resistance genes.

PMID- 16596428
TI  - [Personality, personality disorders and depression].
AB  - Personality is one of most frequently investigated fields in depression research
      and, despite changes in research paradigms, has not lost its relevance. Numerous
      results concerning the conceptualization of conspicuous personality traits, their
      aetiopathogenetic significance, and their effect on treatment and course have
      contributed to a better understanding of depression. Genetics and neurobiology
      provide new incentives for research in this field. We present an overview of
      aspects relevant to personality research in depression including personality
      types, personality traits, temperament factors, and personality disorders.
      Especially results on personality factors' effect on treatment and course of
      depression, integrating these results with different personality models in
      depression, and their consequences to treatment and further research of
      personality traits in depression are discussed.

PMID- 16596430
TI  - Localization of a novel autosomal recessive nonsyndromic hearing impairment locus
      DFNB65 to chromosome 20q13.2-q13.32.
AB  - Autosomal recessive nonsyndromic hearing impairment (ARNSHI) is the most frequent
      form of prelingual hereditary hearing loss in humans. Between 75 and 80% of all
      nonsyndromic deafness is inherited in an autosomal recessive pattern. Using
      linkage analysis, we have mapped a novel gene responsible for this form of
      nonsyndromic hearing impairment, DFNB65, in a consanguineous family from the Azad
      Jammu and Kashmir regions, which border Pakistan and India. A maximum multipoint
      LOD score of 3.3 was obtained at marker D20S840. The three-unit support interval
      is contained between markers D20S902 and D20S430, while the region of
      homozygosity is flanked by markers D20S480 and D20S430. The novel locus maps to a
      10.5-cM region on chromosome 20q13.2-q13.32 and corresponds to a physical map
      distance of 4.3 Mb. DFNB65 represents the first ARNSHI locus to map to chromosome
      20.

PMID- 16596432
TI  - Neurogenic stunned myocardium and transient severe tricuspid regurgitation in a
      child following nonaccidental head trauma.
AB  - Neurogenic stunned myocardium is widely reported in the adult literature and is
      typically associated with subarachnoid hemorrhage. We present a case of
      neurogenic stunned myocardium and transient severe tricuspid regurgitation in a 7
      month-old infant following nonaccidental head trauma.

PMID- 16596433
TI  - Full intrauterine development is compatible with cardia bifida in humans.

PMID- 16596436
TI  - Nonpenetrating clips for end-to-end anastomosis of arteries and veins under
      growing conditions.

PMID- 16596434
TI  - Prospective single-arm protocol of carvedilol in children with ventricular
      dysfunction.
AB  - The objective of this study was to evaluate the safety and efficacy of carvedilol
      in pediatric patients with stable moderate heart failure. We performed a single
      arm prospective drug trial at three academic medical centers and the results were
      compared to historical controls. Patients were 3 months to 17 years old with an
      ejection fraction <40% in the systemic ventricle for at least 3 months on maximal
      medical therapy including ACE inhibitors. Treated patients were started on 0.1
      mg/kg/day and uptitrated to 0.8 mg/kg/day or the maximal tolerated dose.
      Echocardiographic parameters of function were prospectively measured at entry and
      at 6 months. Two composite endpoints were recorded: severe decline in status and
      significant clinical change. Adverse events were reviewed by a safety committee.
      Data were also collected from untreated controls with dilated cardiomyopathy
      meeting entry criteria, assessed over a similar time frame. Twenty patients [12
      dilated cardiomyopathy (DCM) and 8 congenital] with a median age of 8.4 years
      (range, 8 months to 17.8 years) were treated with carvedilol. Three patients
      discontinued the drug during the study. At entry, there was no statistical
      difference in age, weight, or ejection fraction between the treated group and
      controls. The ejection fraction of the treated DCM group improved significantly
      from entry to 6 months (median, 31 to 40%, p = 0.04), with no significant change
      in ejection fraction in the control group [median, 29 to 27%, p = not significant
      (NS)]. The median increase in ejection fraction was larger for the treated DCM
      group than for the untreated DCM controls (7 vs 0%, p = 0.05). By Kaplan-Meier
      analysis, time to death or transplant tended to be longer in treated patients (p
      = 0.07). The difference in the proportion of patients with severe decline in
      status or significant clinical change in the treated group was not significant
      compared to the controls (5 vs 12%, p = NS). We conclude that in this prospective
      protocol of pediatric patients, the use of adjunct carvedilol in the DCM group
      improved ejection fraction compared to untreated controls and trended toward
      delaying time to transplant or death.

PMID- 16596437
TI  - Incorporation of different N sources and light response curves of nitrogenase and
      photosynthesis by cyanobacterial blooms from rice fields.
AB  - In this work, we estimate the contributions of the different sources of N
      incorporated by two N(2)-fixing cyanobacterial blooms (Anabaena sp. and
      Microchaete sp.) in the rice fields of Valencia (Spain) during the crop cycles of
      1999 and 2000, and evaluate the response of nitrogenase and C assimilation
      activities to changing irradiances. Our results show that, far from the generally
      assumed idea that the largest part of the N incorporated by N(2)-fixing
      cyanobacterial blooms in rice fields comes from N(2) fixation, both
      cyanobacterial blooms incorporated about three times more N from dissolved
      combined compounds than from N(2) fixation (only about 33-41% of the N
      incorporated came from N(2) fixation). Our results on the photodependence of C
      and N(2) fixation indicate that in both cyanobacterial blooms, N(2) fixation
      showed a steeper initial slope (alpha) and was saturated with less irradiance
      than C fixation, suggesting that N(2) fixation was more efficient than
      photosynthesis under conditions of light limitation. At saturating light, N(2)
      fixation and C fixation differed depending on the bloom and on the environmental
      conditions created by rice plant growth. Carbon assimilation but not nitrogenase
      activity appeared photoinhibited in the Anabaena but not in the Microchaete bloom
      in August 1999, when the plants were tall and the canopy was important, and there
      was no limitation of dissolved inorganic carbon. The opposite was found in the
      Microchaete bloom of June 2000, when plants were small and produced little shade,
      and dissolved inorganic carbon was very low.

PMID- 16596438
TI  - Bacterial diversity in three different Antarctic Cold Desert mineral soils.
AB  - A bacterial phylogenetic survey of three environmentally distinct Antarctic Dry
      Valley soil biotopes showed a high proportion of so-called "uncultured"
      phylotypes, with a relatively low diversity of identifiable phylotypes.
      Cyanobacterial phylotypic signals were restricted to the high-altitude sample,
      whereas many of the identifiable phylotypes, such as the members of the
      Actinobacteria, were found at all sample sites. Although the presence of
      Cyanobacteria and Actinobacteria is consistent with previous culture-dependent
      studies of microbial diversity in Antarctic Dry Valley mineral soils, many
      phylotypes identified by 16S rDNA analysis were of groups that have not hitherto
      been cultured from Antarctic soils. The general belief that such "extreme"
      environments harbor a relatively low species diversity was supported by the
      calculation of diversity indices. The detection of a substantial number of
      uncultured bacterial phylotypes showing low BLAST identities (< 95%) suggests
      that Antarctic Dry Valley mineral soils harbor a pool of novel psychrotrophic
      taxa.

PMID- 16596440
TI  - Genetic and physiological characterization of the intestinal bacterial microbiota
      of Bluegill (Lepomis macrochirus) with three different feeding habits.
AB  - Bluegill (Lepomis macrochirus) in Lake Biwa, Japan, feed on benthic invertebrates
      (benthivorous type), aquatic plants (herbivorous type), and zooplankton
      (planktivorous type). To evaluate the effect of food on intestinal bacterial
      microbiota, we characterized and compared the intestinal microbiota of these
      three types of bluegill in terms of community-level physiological profile (CLPP)
      and genetic structure. The CLPP was analyzed using Biolog MicroPlates (Biolog,
      Inc., Hayward, CA, USA), and multivariate analysis of variance revealed that the
      CLPP of intestinal microbiota differed significantly between any pairs of the
      three types of bluegill. The genetic profiles were analyzed by temperature
      gradient gel electrophoresis of polymerase chain reaction (PCR)-amplified 16S
      rDNA fragments, and multidimensional scaling indicated the existence of specific
      intestinal bacterial structures for both the benthivorous and the planktivorous
      types. These results suggest that the host's feeding habit can be one factor
      controlling the intestinal microbiota of fish in the natural environment.

PMID- 16596439
TI  - Exploiting new systems-based strategies to elucidate plant-bacterial interactions
      in the rhizosphere.
AB  - The rhizosphere is the site of intense interactions between plant, bacterial, and
      fungal partners. In plant-bacterial interactions, signal molecules exuded by the
      plant affect both primary initiation and subsequent behavior of the bacteria in
      complex beneficial associations such as biocontrol. However, despite this general
      acceptance that plant-root exudates have an effect on the resident bacterial
      populations, very little is still known about the influence of these signals on
      bacterial gene expression and the roles of genes found to have altered expression
      in plant-microbial interactions. Analysis of the rhizospheric communities
      incorporating both established techniques, and recently developed "omic
      technologies" can now facilitate investigations into the molecular basis
      underpinning the establishment of beneficial plant-microbial interactomes in the
      rhizosphere. The understanding of these signaling processes, and the functions
      they regulate, is fundamental to understanding the basis of beneficial microbial
      plant interactions, to overcoming existing limitations, and to designing improved
      strategies for the development of novel Pseudomonas biocontrol strains.

PMID- 16596441
TI  - Aeroterrestrial microalgae growing in biofilms on facades--response to
      temperature and water stress.
AB  - The photosynthetic performance of a microalgal biofilm colonizing a building
      facade was investigated between February and July 2004, with an emphasis on
      changing water availability and air humidity. The fluorimetric measurements of
      the quantum efficiency (F (v)/F (m)) indicated diurnal activity patterns. At most
      sampling dates the algal biofilm photosynthesized particularly in the morning and
      substantially less in the afternoon. As long as liquid water was present, the
      microalgae exhibited at least some degree of photosynthesis. However, F (v)/F (m)
      values never exceeded 0.4, pointing to slight photoinhibition or damage of the
      cells. Dried cells without photosynthesis could recover within minutes after
      artificial moistening. Three microalgal strains were isolated from
      aeroterrestrial biofilms and established as unialgal cultures. Their
      photosynthesis and growth were characterized under different air humidities and
      temperatures. Photosynthesis and growth of strain ROS 55/3 (Stichococcus sp.)
      showed similar patterns with decreasing relative air humidity. Positive growth
      and optimum photosynthesis were recorded at 100% relative air humidity. At air
      humidities below 93%, both processes were strongly inhibited. All studied strains
      grew between 1 and 30 degrees Celsius with optimum rates at 20-23 degrees
      Celsius, indicating eurythermal features. The data indicate that liquid water or
      100% air humidity are the prerequisite for optimum photosynthesis and growth of
      aeroterrestrial microalgae. However, when dried and consequently inactive, these
      microorganisms can recover quickly if water is suddenly available, e.g., after
      rain events. These physiological capabilities explain well the ecological success
      of aeroterrestrial microalgae in occupying many man-made substrata such as
      building facades and roof tiles in urban areas.

PMID- 16596442
TI  - Fast pseudo-periodic oscillation in the rat brain voltage-gated sodium channel
      alpha subunit.
AB  - In the work reported here, we have investigated the changes in the activation and
      fast inactivation properties of the rat brain voltage-gated sodium channel
      (rNa(v) 1.2a) alpha subunit, expressed heterologously in the Chinese Hamster
      Ovary (CHO) cells, by short depolarizing prepulses (10-1000 ms). The time
      constant of recovery from fast inactivation (tau(fast)) and steady-state
      parameters for activation and inactivation varied in a pseudo-oscillatory fashion
      with the duration and amplitude of a sustained prepulse. A consistent oscillation
      was observed in most of the steady-state and non-inactivating current parameters
      with a time period close to 225 ms, although a faster oscillation of time period
      125 ms was observed in the tau(fast). The studies on the non-inactivating current
      and steady-state activation indicate that the phase of oscillation varies from
      cell to cell. Co-expression of the beta1 subunit with the alpha subunit channel
      suppressed the oscillation in the charge movement per single channel and free
      energy of steady-state inactivation, although the oscillation in the half steady
      state inactivation potential remained unaltered. Incidentally, the frequencies of
      oscillation in the sodium channel parameters (4-8 Hz) correspond to the theta
      component of network oscillation. This fast pseudo-oscillatory mechanism,
      together with the slow pseudo-oscillatory mechanism found in these channels
      earlier, may contribute to the oscillations in the firing properties observed in
      various neuronal subtypes and many pathological conditions.

PMID- 16596443
TI  - Hypotonic activation of volume-sensitive outwardly rectifying anion channels
      (VSOACs) requires coordinated remodeling of subcortical and perinuclear actin
      filaments.
AB  - Cell volume regulation requires activation of volume-sensitive outwardly
      rectifying anion channels (VSOACs). The actin cytoskeleton may participate in the
      activation of VSOACs but the roles of the two major actin pools remain undefined.
      We hypothesized that structural reorganization of both subcortical and
      perinuclear actin filaments (F-actin) contributes to the hypotonic activation of
      VSOACs. Hypotonic stress of pulmonary artery smooth muscle cells (PASMCs) was
      associated with reorganization of both peripheral and perinuclear F-actin, and
      with activation of VSOACs. Preincubation with cytochalasin D caused prominent
      dissociation of perinuclear, but not of subcortical F-actin. Cytochalasin D
      failed to induce isotonic activation and delayed the hypotonic activation of
      VSOACs. F-actin stabilization by phalloidin delayed both the hypotonic stress
      induced dissociation of membrane-associated actin filaments and the activation
      kinetics of VSOACs. PKCepsilon, which was proposed to phosphorylate and inhibit
      VSOACs, colocalized primarily with F-actin and the net kinase activity remained
      unchanged during hypotonic cell swelling. In conclusion, normal hypotonic
      activation of VSOACs requires disruption of peripheral F-actin but intact
      perinuclear F-actin; interference with this pattern of actin reorganization
      delays the activation kinetics of VSOACs. The cell swelling-induced peripheral
      actin dissociation may underlie the observed translocation of PKCepsilon, which
      leads to a net decrease of PKCepsilon inhibitory activity in submembranous sites.
      Thus, reorganization of actin and PKCepsilon may establish conditions for mechano
      and/or signal transduction-mediated activation of VSOACs.

PMID- 16596444
TI  - Sodium-dependent potassium channels in leech P neurons.
AB  - In leech P neurons the inhibition of the Na(+)-K(+) pump by ouabain or omission
      of bath K(+) leaves the membrane potential unaffected for a prolonged period or
      even induces a marked membrane hyperpolarization, although the concentration
      gradients for K(+) and Na(+) are attenuated substantially. As shown previously,
      this stabilization of the membrane potential is caused by an increase in the K(+)
      conductance of the plasma membrane, which compensates for the reduction of the
      K(+) gradient. The data presented here strongly suggest that the increased K(+)
      conductance is due to Na(+)-activated K(+) (K(Na)) channels. Specifically, an
      increase in the cytosolic Na(+) concentration ([Na(+)](i)) was paralleled by a
      membrane hyperpolarization, a decrease in the input resistance (R(in)) of the
      cells, and by the occurrence of an outwardly directed membrane current. The
      relationship between R(in) and [Na(+)](i) followed a simple model in which the
      R(in) decrease was attributed to K(+) channels that are activated by the binding
      of three Na(+) ions, with half-maximal activation at [Na(+)](i) between 45 and 70
      mM. At maximum channel activation, R(in) was reduced by more than 90%, suggesting
      a significant contribution of the K(Na) channels to the physiological functioning
      of the cells, although evidence for such a contribution is still lacking.
      Injection experiments showed that the K(Na) channels in leech P neurons are also
      activated by Li(+).

PMID- 16596445
TI  - Local osmosis and isotonic transport.
AB  - Osmotically driven water flow, u (cm/s), between two solutions of identical
      osmolarity, c(o) (300 mM: in mammals), has a theoretical isotonic maximum given
      by u = j/c(o), where j (moles/cm(2)/s) is the rate of salt transport. In many
      experimental studies, transport was found to be indistinguishable from isotonic.
      The purpose of this work is to investigate the conditions for u to approach
      isotonic. A necessary condition is that the membrane salt/water permeability
      ratio, epsilon, must be small: typical physiological values are epsilon = 10(-3)
      to 10(-5), so epsilon is generally small but this is not sufficient to guarantee
      near-isotonic transport. If we consider the simplest model of two series
      membranes, which secrete a tear or drop of sweat (i.e., there are no externally
      imposed boundary conditions on the secretion), diffusion is negligible and the
      predicted osmolarities are: basal = c(o), intracellular approximately (1 +
      epsilon)c(o), secretion approximately (1 + 2epsilon)c(o), and u approximately (1 
      2epsilon)j/c(o). Note that this model is also appropriate when the transported
      solution is experimentally collected. Thus, in the absence of external boundary
      conditions, transport is experimentally indistinguishable from isotonic. However,
      if external boundary conditions set salt concentrations to c(o) on both sides of
      the epithelium, then fluid transport depends on distributed osmotic gradients in
      lateral spaces. If lateral spaces are too short and wide, diffusion dominates
      convection, reduces osmotic gradients and fluid flow is significantly less than
      isotonic. Moreover, because apical and basolateral membrane water fluxes are
      linked by the intracellular osmolarity, water flow is maximum when the total
      water permeability of basolateral membranes equals that of apical membranes. In
      the context of the renal proximal tubule, data suggest it is transporting at near
      optimal conditions. Nevertheless, typical physiological values suggest the newly
      filtered fluid is reabsorbed at a rate u approximately 0.86 j/c(o), so a
      hypertonic solution is being reabsorbed. The osmolarity of the filtrate c(F) (M)
      will therefore diminish with distance from the site of filtration (the
      glomerulus) until the solution being transported is isotonic with the filtrate, u
      = j/c(F).With this steady-state condition, the distributed model becomes
      approximately equivalent to two membranes in series. The osmolarities are now:
      c(F) approximately (1 - 2epsilon)j/c(o), intracellular approximately (1 -
      epsilon)c(o), lateral spaces approximately c(o), and u approximately (1 +
      2epsilon)j/c(o). The change in c(F) is predicted to occur with a length constant
      of about 0.3 cm. Thus, membrane transport tends to adjust transmembrane osmotic
      gradients toward epsilonc(o), which induces water flow that is isotonic to within
      order epsilon. These findings provide a plausible hypothesis on how the proximal
      tubule or other epithelia appear to transport an isotonic solution.

PMID- 16596446
TI  - Roles of aquaporin-3 water channels in volume-regulatory water flow in a human
      epithelial cell line.
AB  - Membrane water transport is an essential event not only in the osmotic cell
      volume change but also in the subsequent cell volume regulation. Here we
      investigated the route of water transport involved in the regulatory volume
      decrease (RVD) that occurs after osmotic swelling in human epithelial Intestine
      407 cells. The diffusion water permeability coefficient (Pd) measured by NMR
      under isotonic conditions was much smaller than the osmotic water permeability
      coefficient (Pf) measured under an osmotic gradient. Temperature dependence of Pf
      showed the Arrhenius activation energy (Ea) of a low value (1.6 kcal/mol). These
      results indicate an involvement of a facilitated diffusion mechanism in osmotic
      water transport. A mercurial water channel blocker (HgCl(2)) diminished the Pf
      value. A non-mercurial sulfhydryl reagent (MMTS) was also effective. These
      blockers of water channels suppressed the RVD. RT-PCR and immunocytochemistry
      demonstrated predominant expression of AQP3 water channel in this cell line.
      Downregulation of AQP3 expression induced by treatment with antisense
      oligodeoxynucleotides was found to suppress the RVD response. Thus, it is
      concluded that AQP3 water channels serve as an essential pathway for volume
      regulatory water transport in, human epithelial cells.

PMID- 16596447
TI  - Inhibition of ClC-2 chloride channels by a peptide component or components of
      scorpion venom.
AB  - ClC chloride channels play essential roles in membrane excitability and
      maintenance of osmotic balance. Despite the recent crystallization of two
      bacterial ClC-like proteins, the gating mechanism for these channels remains
      unclear. In this study we tested scorpion venom for the presence of novel peptide
      inhibitors of ClC channels, which might be useful tools for dissecting the
      mechanisms underlying ClC channel gating. Recently, it has been shown that a
      peptide component of venom from the scorpion L. quinquestriatus hebraeus inhibits
      the CFTR chloride channel from the intracellular side. Using two-electrode
      voltage clamp we studied the effect of scorpion venom on ClC-0, -1, and -2, and
      found both dose- and voltage-dependent inhibition only of ClC-2. Comparison of
      voltage-dependence of inhibition by venom to that of known pore blockers revealed
      opposite voltage dependencies, suggesting different mechanisms of inhibition.
      Kinetic data show that venom induced slower activation kinetics compared to pre
      venom records, suggesting that the active component(s) of venom may function as a
      gating modifier at ClC-2. Trypsinization abolished the inhibitory activity of
      venom, suggesting that the component(s) of scorpion venom that inhibits ClC-2 is
      a peptide.

PMID- 16596448
TI  - Differential effects of ionic strength, divalent cations and pH on the pore
      forming activity of Bacillus thuringiensis insecticidal toxins.
AB  - The combined effects of ionic strength, divalent cations, pH and toxin
      concentration on the pore-forming activity of Cry1Ac and Cry1Ca were studied
      using membrane potential measurements in isolated midguts of Manduca sexta and a
      brush border membrane vesicle osmotic swelling assay. The effects of ionic
      strength and divalent cations were more pronounced at pH 10.5 than at pH 7.5. At
      the higher pH, lowering ionic strength in isolated midguts enhanced Cry1Ac
      activity but decreased considerably that of Cry1Ca. In vesicles, Cry1Ac had a
      stronger pore-forming ability than Cry1Ca at a relatively low ionic strength.
      Increasing ionic strength, however, decreased the rate of pore formation of
      Cry1Ac relative to that of Cry1Ca. The activity of Cry1Ca, which was small at the
      higher pH, was greatly increased by adding calcium or by increasing ionic
      strength. EDTA inhibited Cry1Ac activity at pH 10.5, but not at pH 7.5,
      indicating that trace amounts of divalent cations are necessary for Cry1Ac
      activity at the higher pH. These results, which clearly demonstrate a strong
      effect of ionic strength, divalent cations and pH on the pore-forming activity of
      Cry1Ac and Cry1Ca, stress the importance of electrostatic interactions in the
      mechanism of pore formation by B. thuringiensis toxins.

PMID- 16596449
TI  - Mind the gap: analysis of marker-assisted breeding strategies for inbred mouse
      strains.
AB  - The development of congenic mouse strains is the principal approach for
      confirming and fine mapping quantitative trait loci, as well as for comparing the
      phenotypic effect of a transgene or gene-targeted disruption between different
      inbred mouse strains. The traditional breeding scheme calls for at least nine
      consecutive backcrosses before establishing a congenic mouse strain. Recent
      availability of genome sequence and high-throughput genotyping now permit the use
      of polymorphic DNA markers to reduce this number of backcrosses, and empirical
      data suggest that marker-assisted breeding may require as few as four
      backcrosses. We used simulation studies to investigate the efficiency of
      different marker-assisted breeding schemes by examining the trade-off between the
      number of backcrosses, the number of mice produced per generation, and the number
      of genotypes per mouse required to achieve a quality congenic mouse strain. An
      established model of crossover interference was also incorporated into these
      simulations. The quality of the strain produced was assessed by the probability
      of an undetected region of heterozygosity (i.e., "gaps") in the recipient genetic
      background, while maintaining the desired donor-derived interval. Somewhat
      surprisingly, we found that there is a relatively high probability for undetected
      gaps in potential breeders for establishing a congenic mouse strain. Marker
      assisted breeding may decrease the number of backcross generations required to
      generate a congenic strain, but only additional backcrossing will guarantee a
      reduction in the number and length of undetected gaps harboring contaminating
      donor alleles.

PMID- 16596450
TI  - Data and animal management software for large-scale phenotype screening.
AB  - The mouse N-ethyl-N-nitrosourea (ENU) mutagenesis program at the Genomics
      Institute of the Novartis Research Foundation (GNF) uses MouseTRACS to analyze
      phenotype screens and manage animal husbandry. MouseTRACS is a Web-based
      laboratory informatics system that electronically records and organizes mouse
      colony operations, prints cage cards, tracks inventory, manages requests, and
      reports Institutional Animal Care and Use Committee (IACUC) protocol usage. For
      efficient phenotype screening, MouseTRACS identifies mutants, visualizes data,
      and maps mutations. It displays and integrates phenotype and genotype data using
      likelihood odds ratio (LOD) plots of genetic linkage between genotype and
      phenotype. More detailed mapping intervals show individual single nucleotide
      polymorphism (SNP) markers in the context of phenotype. In addition, dynamically
      generated pedigree diagrams and inventory reports linked to screening results
      summarize the inheritance pattern and the degree of penetrance. MouseTRACS
      displays screening data in tables and uses standard charts such as box plots,
      histograms, scatter plots, and customized charts looking at clustered mice or
      cross pedigree comparisons. In summary, MouseTRACS enables the efficient
      screening, analysis, and management of thousands of animals to find mutant mice
      and identify novel gene functions. MouseTRACS is available under an open source
      license at http://www.mousetracs.sourceforge.net.

PMID- 16596451
TI  - Quantitative trait loci for baseline erythroid traits.
AB  - A substantial genetic contribution underlies variation in baseline peripheral
      blood counts. We performed quantitative trait locus/loci (QTL) analyses to
      identify chromosome (Chr) regions harboring genes influencing the baseline
      erythroid parameters in F2 intercrosses between NZW/LacJ, SM/J, and C57BLKS/J
      inbred mice. We identified multiple significant QTL for red blood cell (RBC)
      count, hemoglobin (Hgb) and hematocrit (Hct) levels, mean corpuscular volume
      (MCV), mean corpuscular hemoglobin (MCH), and mean cell hemoglobin concentration
      (CHCM). We identified four RBC count QTL: Rbcq1 (Chr 1, peak LOD score at 62
      cM,), Rbcq2 (Chr 4, 60 cM), Rbcq3 (Chr 11, 34 cM), and Rbcq4 (Chr 10, 60 cM).
      Three MCV QTL were identified: Mcvq1 (Chr 7, 30 cM), Mvcq2 (Chr 11, 6 cM), and
      Mcvq3 (Chr 10, 60 cM). Single significant loci for Hgb (Hgbq1, Chr 16, 32 cM),
      Hct (Hctq1, Chr 3, 42 cM), and MCH (Mchq1, Chr 10, 60 cM) were identified. The
      data support the existence of a common RBC/MCH/MCV locus on Chr 10. Two QTL for
      CHCM (Chcmq1, Chr 2, 48 cM; Chcmq2, Chr 9, 44 cM) and an interaction between
      Chcmq2 with a locus on Chr 19 were identified. These analyses emphasize the
      genetic complexity underlying the regulation of erythroid peripheral blood traits
      in normal populations and suggest that genes not previously recognized as
      significantly impacting normal erythropoiesis exist.

PMID- 16596452
TI  - Genetic identification of distinct loci controlling mammary tumor multiplicity,
      latency, and aggressiveness in the rat.
AB  - The rat is considered an excellent model for studying human breast cancer.
      Therefore, understanding the genetic basis of susceptibility to mammary cancer in
      this species is of great interest. Previous studies based on crosses involving
      the susceptible strain WF (crossed with the resistant strains COP or WKY) and
      focusing on tumor multiplicity as the susceptibility phenotype led to the
      identification of several loci that control chemically induced mammary cancer.
      The present study was aimed to determine whether other loci can be identified by
      analyzing crosses derived from another susceptible strain on the one hand, and by
      including phenotypes other than tumor multiplicity on the other hand. A backcross
      was generated between the susceptible SPRD-Cu3 strain and the resistant WKY
      strain. Female progeny were genotyped with microsatellite markers covering all
      rat autosomes, treated with a single dose of DMBA, and phenotyped with respect to
      tumor latency, tumor multiplicity, and tumor aggressiveness. Seven loci
      controlling mammary tumor development were detected. Different loci control tumor
      multiplicity, latency, and aggressiveness. While some of these loci colocalize
      with loci identified in crosses involving the susceptible strain WF, new loci
      have been uncovered, indicating that the use of distinct susceptible and
      resistant strain pairs will help in establishing a comprehensive inventory of
      mammary cancer susceptibility loci.

PMID- 16596453
TI  - The human FK506-binding proteins: characterization of human FKBP19.
AB  - Analysis of the human repertoire of the FK506-binding protein (FKBP) family of
      peptidyl-prolyl cis/trans isomerases has identified an expansion of genes that
      code for human FKBPs in the secretory pathway. There are distinct differences in
      tissue distribution and expression levels of each variant. In this article we
      describe the characterization of human FKBP19 (Entrez Gene ID: FKBP11), an FK506
      binding protein predominantly expressed in vertebrate secretory tissues. The
      FKBP19 sequence comprises a cleavable N-terminal signal sequence followed by a
      putative peptidyl-prolyl cis/trans isomerase domain with homology to FKBP12. This
      domain binds FK506 weakly in vitro. FKBP19 mRNA is abundant in human pancreas and
      other secretory tissues and high levels of FKBP19 protein are detected in the
      acinar cells of mouse pancreas.

PMID- 16596454
TI  - Bioinformatic and expression analysis of novel porcine beta-defensins.
AB  - Beta-defensins are a major group of mammalian antimicrobial peptides. Although
      more than 30 beta-defensins have been identified in humans, only one porcine beta
      defensin has been reported. In this article we report the identification and
      initial characterization of 11 novel porcine beta-defensins (pBD). Using
      bioinformatic approaches, we screened 287,821 porcine expressed sequence tags for
      similarity of their predicted peptides to known human beta-defensins and
      identified full-length or partial sequences for the 11 novel pBDs. Similar to the
      previously identified pBD1, all of these peptides have a consensus beta-defensin
      motif. A differential expression pattern for these newly identified genes was
      found. For example, unlike most beta-defensins, pBD2 and pBD3 were expressed in
      bone marrow and in other lymphoid tissues including thymus, spleen, lymph nodes,
      duodenum, and liver. Including pBD2 and pBD3, six porcine beta-defensins were
      expressed in lung and skin. Several newly identified porcine beta-defensins,
      including pBD123, pBD125, and pBD129, were expressed in male reproductive
      tissues, including lobuli testis and some segments of the epididymis.
      Phylogenetic analysis indicates that in most cases the evolutionary relationship
      between individual porcine beta-defensins and their human orthologs is closer
      than the relationship among beta-defensins in the same species. These findings
      establish the existence of multiple porcine beta-defensins and suggest that the
      pig may be an ideal model for the characterization of beta-defensin diversity and
      function.

PMID- 16596455
TI  - Linkage analysis with an interbreed backcross maps Dalmatian hyperuricosuria to
      CFA03.
AB  - Dalmatians, like humans, excrete uric acid in their urine. All other dogs and
      most mammals excrete allantoin, a water-soluble compound that is further along
      the purine degradation pathway. Excretion of uric acid at high concentrations
      (hyperuricosuria) predisposes Dalmatians to the formation of urinary urate
      calculi. Hyperuricosuria (huu) is found in all Dalmatians tested and is inherited
      as an autosomal recessive trait. A genome scan and linkage analysis performed on
      a Dalmatian x Pointer interbreed backcross detected a single linked marker,
      REN153P03, located on CFA03. Haplotype analysis of the region around this marker
      defined a 3.3-Mb interval flanked by single recombination events. This interval,
      which contains the huu mutation, is estimated to include 24 genes.

PMID- 16596457
TI  - Detection of heterogeneities embedded within a turbid slab media using time- and
      frequency-domain methods: application to the mammography.
AB  - During the last decade, several methods have been devoted to the detection and
      imaging of tumor-like objects embedded in turbid slab media. Optical methods are
      broadly investigated as potential non-invasive medical diagnosis used for the
      detection of tumors. In this paper, we model the photon migration due to a pulsed
      source laser, through a multiple scattering slab to locate and characterize
      heterogeneities of different optical properties. The time-dependent diffusion
      equation is used and solved by means of a finite element model, taking into
      account air-tissue boundary conditions. The transmitted time-spectra associated
      to their Fast Fourier Transforms are used to detect embedded objects within
      diffusive slab media. We show that for an inclusion of identical scattering
      coefficient to the surrounding medium, the phase shift increases as the
      absorption coefficient of the inclusion is increased. For a homogeneous
      absorption, the phase shift is very sensitive to local variations in scattering
      properties. We then compare these results with those reported by other workers
      and conclude that the computational model allows the lateral detection of these
      inclusions, so it should be possible to enhance the detection of a malignant
      tumor surrounded by the healthy breast tissue.

PMID- 16596456
TI  - Examination of a region showing linkage map discrepancies across sheep breeds.
AB  - The availability of accurate linkage maps is an important step for the
      localization of genetic variants of interest. However, most studies in livestock
      assume the published map is applicable in their population despite the large
      differences between the breeds of a species. A region of sheep Chromosome 1 was
      previously identified as providing evidence for a marker order inconsistent with
      the published linkage map. In this study the identified region was investigated
      in more detail. Four microsatellite markers covering the central 5 cM of the
      inconsistent region and two flanking markers were genotyped in three sheep
      breeds, a commercial population (Charollais), an experimental population
      (Scottish Blackface), and a feral population (Soay). With the inclusion of the
      published linkage map, this provided evidence for three different marker orders
      across four sheep populations. Evidence for selection in this region was
      investigated using both a single-point allelic competition model and a multipoint
      allele-sharing statistic. Only the Charollais population provided evidence for
      selection, with significant transmission bias observed at marker BM7145. The
      implications of variation in linkage maps on the design and analysis of fine
      mapping studies are discussed.

PMID- 16596459
TI  - Significance of tension in tension-free mid-urethral sling procedures: a
      preliminary study.
AB  - We report the results of the release and tape-shortening techniques in
      polypropylene pubovaginal slings. Of female patients who had undergone mid
      urethral sling procedures [tension-free vaginal tape procedure and suburethral
      polypropylene (SPARC)], in cases in which postoperative retention occurred, the
      patients were offered release or tape cutting. Women reporting postoperative
      urinary incontinence underwent a tape-shortening procedure. In these patients,
      the tape was shortened by the use of clips. Mean follow-up time after the release
      and/or the shortening operations was 9.9 months (range 6-18). A total of 15
      women, ranging from 41 to 75 years old (mean 58.3) were included in this study.
      Upon the latest follow-up, six women exhibited prolonged urinary retention and
      subsequently underwent a release procedure (n=5) or a tape-cutting procedure
      (n=1). After the release procedure, all patients remained continent, but one
      patient's urinary retention issues were not resolved, and she subsequently
      underwent a tape-cutting. Both of the patients who underwent the cutting
      procedure then developed recurrent stress urinary incontinence. The tape
      shortening technique was conducted with nine patients. Seven of these patients
      recovered their continence, and no one patient experienced any urinary retention
      or other voiding difficulties. Two patients reported only minimal stress leakage
      and elected to undergo no further interventions. Our findings suggest that
      tension plays a substantial role in tension-free mid-urethral sling procedures.

PMID- 16596458
TI  - Has the true prevalence of voiding difficulty in urogynecology patients been
      underestimated?
AB  - Voiding difficulty has been relatively overlooked as a diagnosis. Previous
      estimates of its prevalence have generally been no more than 14% with one
      exception at 24%. The aim of this study is to determine the true prevalence and
      associations of voiding difficulty using a validated definition [urine flow rate
      under 10th centile of the Liverpool Nomograms and/or residual urine volume (by
      transvaginal ultrasound) more than 30 ml]. This study involved 592 women referred
      for an initial urogynecological assessment including urodynamics. Data were
      separated according to the presence or absence of voiding difficulty. The
      prevalence of voiding difficulty was 39%, far higher than previous estimates. It
      is the third most common urodynamic diagnosis behind urodynamic stress
      incontinence (USI-72%) and uterine/vaginal prolapse (61%) and ahead of the
      overactive bladder (13%). Voiding difficulty significantly increased in
      prevalence with age and increasing grades of all types of uterine/vaginal
      prolapse. Prolapse appeared to be the main factor in the age deterioration. Other
      significant positive relationships with voiding difficulty were prior
      hysterectomy and prior continence surgery, whilst USI and the symptom and sign of
      stress incontinence had significant inverse relationships.

PMID- 16596460
TI  - Voiding dysfunction after abdominoplasty--an unusual complication.
AB  - Abdominoplasty is an electively undertaken aesthetic operation mostly performed
      on patients after massive weight reduction. Previous case reports have
      demonstrated an improvement of incontinence symptoms after abdominoplasty. We
      report a case where urinary dysfunction occurred after refashioning of an
      abdominoplasty. The stress urinary incontinence got worse but what was of greater
      concern to her was a noticeable change of her urinary stream in an upward
      direction. A urethrolysis combined with an insertion of a tension-free vaginal
      tape and an anterior colporrhaphy was performed. After the operation, stress
      urinary incontinence improved and she reported that her urine stream reverted
      towards a normal direction.

PMID- 16596461
TI  - Vitamin D insufficiency and the blunted PTH response in established osteoporosis:
      the role of magnesium deficiency.
AB  - INTRODUCTION: Vitamin D insufficiency is common, however within individuals, not
      all manifest the biochemical effects of PTH excess. This further extends to
      patients with established osteoporosis. The mechanism underlying the blunted PTH
      response is unclear but may be related to magnesium (Mg) deficiency. The aims of
      this study were to compare in patients with established osteoporosis and
      differing degrees of vitamin D and PTH status : (1) the presence of Mg deficiency
      using the standard Mg loading test (2) evaluate the effects of Mg loading on the
      calcium-PTH endocrine axis (3) determine the effects of oral, short term Mg
      supplementation on the calcium-PTH endocrine axis and bone turnover. METHODS: 30
      patients (10 women in 3 groups) were evaluated prospectively measuring calcium,
      PTH, Mg retention (Mg loading test), dietary nutrient intake (calcium, vitamin D,
      Mg) and bone turnover markers (serum CTX & P1CP). Multivariate analysis
      controlling for potential confounding baseline variable was undertaken for the
      measured outcomes. RESULTS: All subjects, within the low vitamin D and low PTH
      group following the magnesium loading test had evidence of Mg depletion [mean(SD)
      retention 70.3%(12.5)] and showed an increase in calcium 0.06(0.01) mmol/l [95%
      CI 0.03, 0.09, p=0.007], together with a rise in PTH 13.3 ng/l (4.5) [95% CI 3.2,
      23.4, p=0.016] compared to baseline. Following oral supplementation bone turnover
      increased: CTX 0.16 (0.06) mcg/l [95%CI 0.01, 0.32 p=0.047]; P1CP 13.1 (5.7)
      mcg/l [95% CI 0.29, 26.6 p=0.049]. In subjects with a low vitamin D and raised
      PTH mean retention was 55.9%(14.8) and in the vitamin replete group 36.1%(14.4),
      with little change in both acute markers of calcium homeostasis and bone turnover
      markers following both the loading test and oral supplementation. CONCLUSIONS:
      This study confirms that in patients with established osteoporosis, there is also
      a distinct group with a low vitamin D and a blunted PTH level and that Mg
      deficiency (as measured by the Mg loading test) is an important contributing
      factor.

PMID- 16596463
TI  - Food transfers in immature wild western lowland gorillas (Gorilla gorilla
      gorilla).
AB  - The transfer of food items between individuals has been described in primates as
      serving an informative purpose in addition to supplementing the diet of immature
      individuals. This behaviour has yet to be described in western lowland gorillas
      (Gorilla gorilla gorilla), and results are presented here of observations of food
      transfers in immature gorillas at Mbeli Bai, Republic of Congo. The frequency of
      food transfers decreased with increasing immature age, while the frequency of
      independent feeding and processing of food increased. Transfers between mothers
      and infants were the most frequent, with infants attempting to take items from
      the mother. These attempts were not always successful and the item was
      relinquished on less than 50% of attempts. Mothers also took items from their
      offspring. The results point to the functional significance of food transfers in
      western lowland gorillas being informational. In a bai environment, where one
      species forms the majority of a visiting gorilla's diet despite other species
      being available, the initiation of food transfers by immatures is proposed to
      serve the purpose of familiarising them with which species, and which parts of
      those species, may be eaten.

PMID- 16596462
TI  - Treatment of osteoporosis with TheraCyte-encapsulated parathyroid cells: a study
      in a rat model.
AB  - INTRODUCTION: The purpose of this study was to evaluate parathyroid function at
      monthly intervals following the implantation of TheraCyte-encapsulated live human
      parathyroid cells into ovariectomized rats and to determine the effect on bone
      mineral density (BMD) 4 months after ovariectomy ( 3 months after implantation).
      METHODS: Parathyroid tissues were obtained from patients undergoing surgery for
      secondary hyperparathyroidism. In total, 21 Sprague-Dawley rats divided randomly
      into three groups were subjected to one of three treatments: (1) implanted with
      TheraCyte A-encapsulated 4x10(6) live parathyroid cells; (2) implanted with
      TheraCyte B-encapsulated 4x10(5) live parathyroid cells; (3) a sham operation;
      the control group. Rats were ovariectomized 1 month prior to the implantation of
      the TheraCyte. Blood was drawn at the time of implantation and at monthly
      intervals thereafter for 3 months to check the levels of calcium, phosphorus and
      intact parathyroid hormone (iPTH). The BMD of the lumbar spine (L1-L5) and of the
      left femoral bone was measured with dual-energy-X-ray absorptiometry (DEXA) 1
      month after ovariectomy and 3 months after implantation of the TheraCyte (4
      months after ovariectomy). RESULTS: We found that the viability ratio of
      cryopreserved tissues was between 55 and 79% after thawing. In the control group,
      the BMD of the lumbar spine (L1-L5) had not decreased significantly (p=0.237) nor
      had the BMD of the left femoral bone increased significantly (p=0.063) 3 months
      after implantation. In the TheraCyte A group, the BMD of both the lumbar spine
      (p=0.018) and left femoral bone (p=0.018) had increased significantly 3 months
      after implantation. In the TheraCyte B group, the BMD of both the lumbar spine
      (p=0.017) and the left femoral bone (p=0.025) had also increased significantly 3
      months after implantation. Serum iPTH levels were higher in the TheraCyte A group
      than in the TheraCyte B group (p=0.006), and higher in the TheraCyte B group than
      in the control group (p=0.040). Serum calcium levels were not significantly
      higher in the TheraCyte group A than in the TheraCyte B group or in the control
      group. Serum phosphorus levels were not significantly different between the
      TheraCyte A and TheraCyte B groups. CONCLUSIONS: Implantation of TheraCyte A
      encapsulated 4x10(5) live parathyroid cells and TheraCyte B-encapsulated 4x10(6)
      cells can increase the BMD of ovariectomized rats within 3 months of
      implantation. Neither cause high serum calcium and low phosphorus concentrations.

PMID- 16596464
TI  - Clinical experiences with the PDDST-II.

PMID- 16596465
TI  - A crossover study of risperidone in children, adolescents and adults with mental
      retardation.
AB  - Risperidone has shown safety and efficacy for aggressive and destructive
      behaviors in short-term studies. This longer-duration study includes a broad
      sample. Forty subjects, aged 8-56 years (mean=22), all with mental retardation
      and 36 with autism spectrum disorders participated in this 22-week crossover
      study, with 24 weeks of open maintenance thereafter. Of 40 subjects, 23 (57.5%)
      responded fully (50% decrease in Aberrant Behavior Checklist-Community
      Irritability subscale score), while 35 subjects (87.5%) showed a 25% decrease.
      Gender, mood disorder, and antiseizure medications did not alter response.
      Increased appetite and weight gain were common. Low dose risperidone was
      effective for aggressive behavior in persons with MR. More long-term studies are
      needed, incorporating weight control interventions.

PMID- 16596466
TI  - A subtelomeric translocation apparently implied in multiple abortions.
AB  - PURPOSE: Chromosomal alterations are a major cause of clinically recognized
      abortions. So cryptic chromosomal rearrangements could be responsible for
      recurrent miscarriages. METHODS: The study was performed on 18 clinically normal
      couples who had four or more spontaneous abortions and whose karyotypes were
      found to be normal. Fluorescence in situ hybridization with specific probes of
      subtelomeric regions was used after optimizing the amount of probe. RESULTS: Only
      one subtelomeric translocation was detected between 2p and 3p chromosomes, in a
      female with seven miscarriages. CONCLUSION: Subtelomeric rearrangements are
      infrequently related to multiple miscarriages. This kind of studies can be
      considered specially worthy when a couple have had not only abortions but also
      offspring with mental and physical anomalies. Thus, possible initial studies
      should focus on affected children or fetus.

PMID- 16596467
TI  - Physical environment and crime and misconduct in Kentucky schools.
AB  - Drawing upon ecological theories of crime control, aspects of the physical
      environment such as building design, street layout, and land use are thought to
      indicate territoriality and natural surveillance, thereby affecting the ability
      of residents to supervise and intervene in crime. To date, ecological models have
      been tested primarily at community levels of analysis (i.e., neighborhood,
      block). In contrast, this paper tests the applicability of this theoretical
      approach to crime in school settings. More specifically, we estimate random
      intercept models using survey data from 3682 7th-grade students and 1351
      teachers, nested within 65 Kentucky schools linked to school-level measures of
      the physical environment to determine how they affect various measures of school
      based crime and misconduct. Editors' Strategic Implications:How one measures
      school violence may have profound effects on what contributing causal factors are
      identified and strategies for prevention are developed. Student reports of school
      violence appear linked to more normative daily behaviors, whereas teacher reports
      though limited to officially observed behaviors-are typically more serious. Thus,
      measurement implications abound. Nevertheless, territoriality, surveillance, and
      a sense of order, particularly in the immediate school context more so than the
      larger community context, appear linked to school violence.

PMID- 16596468
TI  - Predictors of aggressive behaviors among rural middle school youth.
AB  - This study determined multivariate sets of predictors for verbal and physical
      aggression among rural middle school youth. Surveys were obtained from 1,440 7th
      and 8th grade youth from six middle schools in five geographically dispersed
      states. Multivariate logistic regression identified final predictive models.
      Similar, but varying sets of predictors were identified across types of
      aggression. The most consistent set of predictors was gender, family actions
      against violence, peer violence, anger, academic performance, and alcohol use.
      These results suggest that in comparison with past studies of non-rural youth,
      similar factors predict aggressive behavior among urban and non-urban youth.
      Editors' Strategic Implications: This paper makes two contributions to our
      understanding of the contextual factors influencing youth violence. First, it
      indicates that the predictive factors for rural and non-rural youth violence are
      similar. Second, it confirms the role of both family and peers in influencing
      such violence. Those who design and implement programs and polices addressing
      youth violence must look beyond individual variables in order to create
      comprehensive strategies.

PMID- 16596469
TI  - Feeding behavior of lambs in relation to kinetics of 1,8-cineole dosed
      intravenously or into the rumen.
AB  - The monoterpene 1,8-cineole is a major constituent of the essential oils that
      adversely influence intake of sage brush by herbivores, but little is known about
      the mechanisms of its action. We investigated the influence of 1,8-cineole on the
      feeding behavior of two groups of sheep, one group dosed intravenously and the
      other intra-ruminally. In the first study, we infused 40 mg/kg BW of 1,8-cineole
      intravenously into four lambs on wk 1, 2, and 4. In the second, we administered
      125 mg/kg BW of 1,8-cineole into the rumen of four lambs as a single-bolus dose
      in wk 1 and 2. Lambs dosed intravenously spent less time feeding than controls
      (28 vs. 60 min; P<0.05), as did lambs dosed intra-ruminally (35 vs. 60 min;
      P<0.05). Dosed lambs ate less than controls during rumen dosing studies (P<0.05).
      For the intravenous infusion studies, rates of elimination did not differ among
      weeks (P<0.05). For the rumen infusion studies, however, the absorption rate
      constant increased from 0.035/min to 0.076/min from wk 1 to 2, while the
      absorption half-life declined from 24 to 10 min (P<0.05). Maximum plasma
      concentrations and time to reach maximum plasma concentrations were no faster in
      wk 2 than wk 1, but the primary elimination rate constant was 2.3 times higher in
      wk 2 (0.058/min) than in wk 1 (0.025/min) (P<0.05). Dosed lambs exhibited
      clinical effects-licking of lips, drowsiness, staggering, and 1,8-cineole
      smelling breath-that were much more pronounced with intravenous than rumen
      infusions. Dosing did not affect the acid-base balance. Collectively, these data
      suggest 1) rapid absorption and distribution of 1,8-cineole was responsible for
      initiating satiety, while more prolonged excretion was responsible for the
      duration of the satiety effect, and 2) lambs more readily adapted to 1,8-cineole
      in the rumen-dose study than in the intravenous-dose study.

PMID- 16596471
TI  - Trisomy 21: from chromosomes to mental retardation.
AB  - The first descriptions of the trisomy 21 phenotype were by Jean-Etienne-Dominique
      Esquirol (1838), Edouard Seguin (1846) and later by John L. H. Down in 1862. It
      took more than a century to discover the extra-chromosomal origin of the syndrome
      commonly called "Down's syndrome" and which, we suggest, should be referred to as
      "Trisomy 21". In this review we are presenting the landmarks, from the pioneering
      description of the syndrome in 1838 to Jerome Lejeune's discovery of the first
      genetic substrate for mental retardation. The sequencing of HSA21 was a new
      starting point that generated transcriptome studies, and we have noted that
      studies of gene over-expression have provided the impetus for discovering the
      HSA21 genes associated with trisomy 21 cognitive impairment.

PMID- 16596470
TI  - Clustering of health-related behaviors and their determinants: possible
      consequences for school health interventions.
AB  - Characterizing school health promotion is its category-by-category approach, in
      which each separate health-related behavior is addressed independently. Such an
      approach creates a risk that extra-curricular activities become overloaded, and
      that teaching staff are distracted by continuous innovations. Within the health
      promotion sector there are thus increasing calls for an integrative approach to
      health-related behaviors. However, a meaningful integrative approach to different
      lifestyles will be possible only if there is some clustering of individual health
      related behaviors and if health-related behaviors have a minimum number of
      determinants in common. This systematic review aims to identify to what extent
      the four health-related behaviors smoking, alcohol abuse, safe sex and healthy
      nutrition cluster; and how their determinants are associated. Potentially
      modifiable determinants that offer clues for an integrative approach of school
      health-promotion programs are identified. Besides, the direction in which health
      educators should look for a more efficient instructional design is indicated.

PMID- 16596472
TI  - TGFbeta in cancer and other disease - AACR special conference in cancer research.

PMID- 16596473
TI  - Hematologic malignancies: from clinical science to clinical practice - 2nd
      European Congress.

PMID- 16596474
TI  - Stroke - international conference 2006.

PMID- 16596475
TI  - Retroviruses and opportunistic infections - 13th annual meeting.

PMID- 16596476
TI  - Translational medicine 2006.

PMID- 16596477
TI  - Drug discovery technology Europe 2006 - IBC's Tenth Annual Conference and
      Exhibition.

PMID- 16596478
TI  - Drug Design V - SMi Conference.

PMID- 16596479
TI  - Market opportunities and technology trends in point of care diagnostics - SMi
      conference.

PMID- 16596480
TI  - Functional protein arrays to facilitate drug discovery and development.
AB  - Protein microarrays are miniaturized formats for studying proteins. This
      technology is empowering investigators with the ability to profile numerous types
      of interactions to progress basic science research and to advance drug discovery
      and development. Protein microarrays are poised to make significant contributions
      to our understanding of biology and disease because: (i) both covalent and non
      covalent interactions can be reconstituted on solid-state supports; and (ii) a
      wealth of knowledge can be generated rapidly from such simple experiments. This
      feature focuses on applications of protein microarrays that have tremendous
      potential for addressing bottlenecks in disease-focused discovery efforts.

PMID- 16596481
TI  - Structure-based discovery and optimization of potential cancer therapeutics
      targeting the cell cycle.
AB  - Progress has been made recently in the structure-based optimization of novel cell
      cycle antitumor therapeutics based on cyclin-dependent kinase (CDK) inhibition. A
      novel inhibitor series based on the 2-amino-4-heteroaryl-pyrimidine scaffold was
      discovered using the LIDAEUS high-throughput docking methodology, and was
      subsequently optimized for CDK2 potency through information provided by
      crystallographic complex structures. A computational study of CDK4 inhibitors led
      to the incorporation of selectivity determinants into a pyrimidine pharmacophore
      to generate isoform-specific inhibitors. In addition, molecules from the
      inhibitor series have been crystallized in complex structures with both monomeric
      inactive CDK2 and an active complex of CDK2 bound to cyclin A or E. This
      crystallization revealed that significant differences exist in the affinity of
      the inhibitors for active and inactive states of CDK2. Information on differences
      in affinity facilitates the prediction of experimental binding of inhibitors and
      allows for the further development of structure-guided design.

PMID- 16596482
TI  - Using RNAi in the clinic.
AB  - RNA interference (RNAi) is a biological process that controls gene silencing in
      all living cells. Targeting the RNAi system represents a novel therapeutic
      strategy that has the ability to intercede with multiple disease-related genes
      and so target many human diseases. Recently, the design of small interfering RNA
      (siRNA)-selective compounds has become more straightforward because of the
      significant progress made in predictive modeling. Exciting new data show that
      siRNA blocks gene function in vivo, suggesting that it has potential as a
      therapeutic approach for humans. This article highlights recent advances in siRNA
      research and discusses the aims of the pharmaceutical and biotechnology
      industries to progress siRNA compounds into the clinical. In the fight against
      disease, the use of RNAi is a powerful new tactic that adds to the arsenal of
      small-molecule inhibitors and antibody-blocking approaches.

PMID- 16596483
TI  - TRX-4 (TolerRx Inc).
AB  - TolerRx Inc, under license from BTG plc, is developing TRX-4, an anti-CD3
      humanized monoclonal antibody for the potential treatment of type 1 diabetes and
      psoriasis. Phase II trials of the therapeutic antibody in type 1 diabetes have
      been completed and the company is planning a pivotal phase III trial for this
      indication. TolerRx is also enrolling psoriasis patients in a phase Ib clinical
      study of TRX-4. TRX-4 has been awarded Orphan Drug status for recent-onset type 1
      diabetes.

PMID- 16596485
TI  - Spontaneous version following preterm premature rupture of membranes.
AB  - Our objective was to determine the rate of spontaneous version following preterm
      premature rupture of membranes (PPROM). Medical charts over a 4-year period were
      reviewed. All women with PPROM and singleton gestation between 24 and 34 weeks
      gestation were included; 65 patients met the inclusion criteria. By ultrasound on
      admission, 48 were cephalic 16 were breech, and one was transverse lie. Mean
      amniotic fluid index on admission was 5.1 +/- 4.8 cm (standard deviation) and was
      not associated with fetal presentation at delivery. Spontaneous version from
      cephalic presentation at admission to noncephalic presentation at delivery
      occurred in one pregnancy (2.2%). Spontaneous version from noncephalic
      presentation at admission to cephalic presentation at delivery occurred in three
      pregnancies (17.6%; p = 0.05). Among women with noncephalic presentation at
      delivery (n = 15), 73.3% had a cesarean, compared with 23.4% of those with
      cephalic presentation at delivery (p < 0.05). Spontaneous version, particularly
      from cephalic to noncephalic presentation, is unlikely following PPROM.

PMID- 16596486
TI  - Inpatient versus outpatient management of monoamniotic twins and outcomes.
AB  - We sought to evaluate whether early (24 to 28 weeks gestation) hospitalization of
      monoamniotic twins, with close fetal surveillance, and delivery at 32 to 34 weeks
      gestation, would significantly improve the perinatal morbidity and mortality
      compared with an outpatient management strategy. A multicenter, retrospective
      record review was undertaken. Records of all monoamniotic twins were collected
      for a 10-year period. Monoamniotic twins were identified using intensive care
      nursery, ultrasound, and pathology records. Data were collected on inpatient
      versus outpatient management strategies and the perinatal/maternal outcomes and
      complications. Twenty-three sets of monoamniotic twins were included in the
      study. Eleven sets were managed using an inpatient strategy and 12 sets were
      managed using an outpatient strategy. There were no fetal deaths in the inpatient
      group and there were three fetal deaths in the outpatient group. Inpatient
      management of monoamniotic twins should be considered.

PMID- 16596484
TI  - Severe neonatal hemolysis due to a maternal antibody to the low-frequency Rh
      antigen C(w).
AB  - C(w) is a low-frequency antigen in the Rh blood group system with a prevalence of
      approximately 2% in whites. Although anti-C(w) is not an uncommon antibody in
      pregnancy (0.1% incidence), clinically significant hemolytic disease of the
      newborn is highly unusual. We report the case of an infant with severe
      hyperbilirubinemia and persistent anemia due to a high-titer maternal C(w)
      antibody. The medical literature relating to maternal C(w) alloimmunization and
      neonatal outcome is also reviewed. In addition, recommendations are made
      regarding the management of pregnancies and newborns complicated by antibodies to
      C(w).

PMID- 16596488
TI  - [Stent-graft implantation in the thoracic aorta. Results of an interdisciplinary
      survey in Germany].
AB  - BACKGROUND AND OBJECTIVE: Endovascular stent-graft placement is emerging as a
      novel therapeutic option in patients with disease of the descending thoracic
      aorta. Quality standards for performing stent-graft procedures as well as for pre
      and postoperative patient management are lacking, so far. It was the aim of this
      present survey to assess the current therapeutic standard of thoracic aortic
      stent-graft placement in Germany. METHODS: In a nationwide survey, a total of 206
      vascular surgical, radiologic, cardiologic, and cardiothoracic surgical
      departments were contacted. Data concerning preoperative procedure planning,
      logistics, practical/technical issues of stent-graft placement, and postoperative
      patient management were evaluated using a standardized questionnaire comprising
      29 items. Data analysis was performed using univariate analysis. RESULTS: 184
      (89.3 %) of the 206 departments participated in the survey. Of these, 71 centers
      reported intending to perform or having performed thoracic aortic stent-graft
      placement. The survey overall represents 2267 endovascular stent-graft procedures
      performed in Germany between 1997/98 and 2003. On average, 7.4 stent-graft
      procedures/year were performed by each center, with half the centers performing
      fewer than 5 procedures/year. Thoracic aortic aneurysms was the main indication
      for endovascular stent-graft placement, followed by aortic dissection. There were
      significant differences between the different medical specialties which perform
      stent-graft procedures with respect to indications, choice of preoperative and
      intraoperative imaging methods, and technical equipment. There was strong
      agreement between the different centers concerning the necessity of a life-long
      follow-up after stent-graft placement, with computed tomography being the
      preferred imaging technique (90 % of centers). CONCLUSION: The present survey
      documents an increasing use of endovascular stent-graft placement in patients
      with disease of the descending thoracic aorta. There were differences regarding
      the technical execution of this procedures between specialties with respect to
      indication, procedure planning, and practical-technical aspects of stent-graft
      placement.

PMID- 16596489
TI  - [Tako-Tsubo cardiomyopathy: a differential diagnosis of acute coronary syndrome].
AB  - ANAMNESIS: A 68-year-old woman was admitted to the emergency unit with symptoms
      of an acute coronary syndrome. She complained about a feeling of chest oppression
      for two hours. The cardiac history was unremarkable. Her husband had died few
      hours before the onset of her cardiac symptoms. INVESTIGATIONS: Blood pressure
      was 80/40 mmHg, heart rate 110/min. Cardiac enzymes were normal. The ECG showed
      significant ST elevation in V2 to V6. Laevoangiocardiography revealed a severe
      reduction of left ventricular systolic function with an ejection fraction of 27
      %. Akinesia was seen in the anterior wall region as well as apical, inferior, and
      poserolateral. Coronary heart disease could be excluded. DIAGNOSIS, THERAPY AND
      COURSE: Hemodynamic support with catecholamines was needed for one day. After two
      days hemodynamic recovery occurred. The creatine kinase peak level was
      surprisingly low (357 U/l). Echocardiographies performed in short intervals
      showed a continuous, rapid recovery of the ventricular function. Two weeks later
      the left ventricular function was normal. There was no evidence of myocarditis.
      In consideration of the history of emotional stress, absence of coronary lesions,
      a low CK peak and rapid recovery of left ventricular function, Tako-Tsubo
      cardiomyopathy was diagnosed. Medical treatment with beta blockers was initiated:
      the further clinical course was unremarkable. CONCLUSION: Tako-Tsubo
      cardiomypathy should be considered in patients with findings and symptoms of an
      acute coronary syndrome.

PMID- 16596490
TI  - [Does gender have an effect on pharmacotherapy?].

PMID- 16596491
TI  - [Apical-Ballooning-Syndrome (Tako-Tsubo-Syndrome, neurogenic cardiomyopathy)].

PMID- 16596493
TI  - [Basic cardiopulmonary resuscitation].

PMID- 16596492
TI  - [Pentaerythritol tetranitrate].

PMID- 16596494
TI  - [Blood pressure lowering after stroke].

PMID- 16596495
TI  - [What is the contribution of stress research towards explaining the social
      gradient of coronary heart disease?].

PMID- 16596496
TI  - [Which asymptomatic patient with severe aortic valve stenosis should be treated
      surgically?].

PMID- 16596497
TI  - [Percutaneous closure of patent foramen ovale--For].

PMID- 16596499
TI  - [Cardioverter-defibrillator (ICD) and resynchronization in every patient with
      cardiac failure--For].

PMID- 16596498
TI  - [Percutaneous closure of patent foramen ovale-- Against].

PMID- 16596500
TI  - [Cardioverter-defibrillator (ICD) and resynchronization in every patient with
      cardiac failure--Against].

PMID- 16596501
TI  - [Stem cell transfer after myocardial infarction--For].

PMID- 16596502
TI  - [Stem cell transfer after myocardial infarction--Against].

PMID- 16596503
TI  - [What are the indications and contraindications for vertebroplasty?].

PMID- 16596505
TI  - [Non-invasive assessment of the perfusion of wounds using power Doppler imaging:
      vacuum assisted closure versus direct wound closure].
AB  - AIM: The goal of our study was to assess the perfusion in wounds treated by
      vacuum assisted closure (VAC) compared to primary wound closure. METHOD: Power
      Doppler Ultrasound (PDUS) was carried out under standardised conditions in 15 VAC
      treated and 10 primarily closed wounds as well as on altogether 25
      intraindividual reference areas. All data were sent to a work station for post
      processing to determine the perfused area. Statistical data analysis was
      performed with the Mann-Whitney test. RESULTS: Both VAC-treated wounds and
      primarily closed wounds showed a significant increase of the perfusion when
      compared to the intraindividual reference area (p < 0.0001). In VAC-treated
      wounds, a markedly increased perfusion was measured compared to the wounds closed
      primarily (p < 0.0001). Perfusion decreased during treatment, but in two VAC
      treated wounds, an initial increase of the perfusion was observed. Both these
      wounds were grossly infected. CONCLUSION: PDUS allows the quantification of the
      differences in wound perfusion. This can be helpful in the detection of
      progressive local wound infections.

PMID- 16596507
TI  - [Sonographic diagnosis of parathyroid carcinoma].
AB  - Prognosis and survival of patients suffering from parathyroid carcinoma are
      completely dependent on correct surgical therapy in form of an en-bloc resection
      of the tumour. A correct preoperative diagnosis of this rare carcinoma is
      therefore absolutely mandatory in order to perform a curative operation. We
      demonstrate a case of parathyroid carcinoma in which scintigraphy and CT
      diagnostics did not produce the right diagnosis. Preoperative high-resolution
      ultrasound (8 MHz) in combination with power-Doppler-sonography, however, led to
      the right diagnosis by demonstrating the correct topography, signs of malignancy
      and the feeding vessels of the tumour. As it could be demonstrated that the
      inferior thyroid artery was displaced by the tumour and was not a tumour feeding
      artery, the inferior thyroid artery was an important additional landmark for
      making the decision between thyroid or parathyroid carcinoma. The use of power
      Doppler-sonography for identification of feeding arteries associated with
      parathyroid carcinoma in addition to high-resolution small parts sonography is of
      great value for the distinction between thyroid or parathyroid tumour.

PMID- 16596506
TI  - Detection rate of periintestinal lymph nodes.
AB  - AIM: Compared to standard two-dimensional (2D) endosonography, three-dimensional
      (3D) endosonography has been presented as a possible improvement regarding
      imaging of the gastrointestinal (G-I) tract and detection of metastatic lymph
      nodes. The aim of this study was to evaluate the efficacy of detecting
      periintestinal lymph nodes in surgical specimens using 3D endosonography.
      PATIENTS AND METHODS: Surgical specimens from 31 patients with malignant G-I
      tumours were investigated by 3-D endosonography and histology with focus on the
      presence of periintestinal lymph nodes and presence of metastasis. The specimens
      were scanned submerged into water. Position and size of the lymph nodes were
      mapped on a photo of the specimen both by the pathologist and the examiners.
      RESULTS: Three-dimensional endosonography detected 48 out of 60 malignant lymph
      nodes (80.0 %), and 110 out of 219 benign lymph nodes (50.2 %). The positive
      predictive value for an endosonographic finding interpreted as a lymph node was
      0.97. CONCLUSION: The detection rates for periintestinal lymph nodes were
      relatively high and seemed superior to the one usually assigned to 2D
      endosonography. Although distinguishing between metastatic and non-metastatic
      lymph nodes remains a problem, all patients with histologically confirmed
      metastasis to lymph nodes were detected by 3D endosonography, and the technique
      thus seems suitable for grouping of patients prior to surgery.

PMID- 16596508
TI  - Aortic arch dissection presenting with hemodynamic spectrum of aortic
      regurgitation on transcranial Doppler.
AB  - The diagnosis of aortic dissection is frequently missed at the time of hospital
      admittance. Neurological presentations are rare, and neuro-sonography is rarely
      used. We describe a patient with atypical clinical presentation of aortic arch
      dissection in whom neuro-sonological investigations showed a "cathedral like"
      haemodynamic spectrum of aortic regurgitation, directing the investigation
      towards the diagnosis.

PMID- 16596509
TI  - Transcranial grey-scale sonography of subdural haematoma in adults.
AB  - AIM: Transcranial high-resolution grey-scale sonography reliably allows diagnosis
      and monitoring of subdural haematoma (SDH) and extra-cerebral intracranial fluid
      collections in infants but has not been evaluated thoroughly in adults up to now.
      Because of rapid development of ultrasound systems, the depiction of
      intracerebral haemorrhage (ICH) has now become feasible. The presented study
      evaluated the sonographic appearance of SDH in adults. METHOD: We performed
      transcranial grey-scale sonography (TGS) in 25 consecutive patients with SDH
      confirmed by cranial computed tomography (CCT) or MRI. According to paediatric
      TGS, the dural border of the arachnoid was depicted as a highly echogenic
      membrane, and the distance between the skull and the echogenic membrane was
      measured. SDH was measured by CCT/MRI and by TGS in corresponding axial planes.
      The rate of identification of SDH in TGS was evaluated, and the extent of SDH as
      assessed by CCT/MRI and TGS was compared. RESULTS: TGS reliably detected SDH in
      22 of the 25 patients with confirmed SDH (88 %). In the remaining 3 patients, the
      temporal bone window was insufficient for TGS investigation. Extent of SDH
      measured by CCT and TGS correlated linearly (r= 0.849). CONCLUSION: TGS allows
      imaging of SDH in patients with CCT/MRI confirmed SDH, and the extent of SDH
      correlates significantly between TGS and CCT/MRI. Therefore, TGS may be a
      possible alternative to serial CCT imaging in monitoring SDH, since in contrast
      to CCT, TGS is a non-invasive bedside method. So far, TGS is not suitable for the
      diagnosis of SDH.

PMID- 16596510
TI  - [Correlation between sex, intrauterine position and familial predisposition and
      neonatal hip ultrasound results].
AB  - AIM: To correlate findings of hip ultrasound on day 4-10 of life with sex,
      intrauterine position and a positive family history for congenital hip anomalies.
      METHODS: The SNiP-study ( Survey of Neonates In Pommerania) registered 2256
      neonates (2030 term, 226 preterm) between May 2002 and March 2004. Hip ultrasound
      results of 1043 term and since October 2003 33 preterm neonates were analysed.
      Time of ultrasound was day 4-10 after birth. Preterm neonates were examined when
      reaching their corrected term gestational age. Ultrasound was applied with a 7.5
      MHz linear scanner and results were classified according to Graf. Chi-square and
      Fishers exact test were used for statistical analysis. RESULTS: 4.9 % of the
      screened hips were classified as IIc or higher, 3.1 % were unilateral and 1.7 %
      bilateral. Incidence was significantly higher (p < 0.023) in females (6.6 %) than
      in males (3.2 %). There was no significant difference in intrauterine position or
      positive family history for hip anomalies with 3.7 % for mothers, 1.2 % of
      fathers and 2.4 % of siblings positive. There was a higher incidence for
      congenital hip dysplasia in preterms with 6.1 %, which is not significant due to
      the limited number. DISCUSSION: Current screening methods miss up to 18 % of
      newborns with severe hip dysplasia. We were able to demonstrate that screening
      for congenital hip dysplasia with ultrasound is a diagnostic tool even during the
      first days of life. There is a significantly higher incidence of congenital hip
      dysplasia in females, but in contrast to other studies we found no significant
      difference in intrauterine position or familial history. Earlier diagnosis and
      therapy on the base of relevant risk factors might correspond with an improved
      prognosis and outcome. Further studies are warranted to evaluate the significance
      in preterm neonates.

PMID- 16596511
TI  - Additional performance of nasal bone in first trimester screening.
AB  - OBJECTIVE: To evaluate and compare the screening performance for fetal trisomy 21
      in the first trimester of pregnancy either with or without inclusion of fetal
      nasal bone using two separate risk-algorithms of the Fetal Medicine Foundation
      London (FMF). METHODS: This study included 3174 patients self-referred to our
      tertiary level prenatal centre for first trimester screening at 11-14 weeks of
      gestation between December 1, 2002 and November 30, 2004. Fetal risk for trisomy
      21 was calculated using either the old FMF-algorithm including maternal age,
      nuchal translucency (NT), free ss-human chorionic gonadotropin (hCG), pregnancy
      associated plasma protein-A (PAPP-A) or the new FMF-algorithm using additionally
      the presence or absence of fetal nasal bone (NB). All ultrasonographers were
      certified for measurement of nuchal translucency and nasal bone by the Fetal
      Medicine Foundation Germany. The detection rate for a fixed risk cut-off (1:300)
      and a fixed false-positive rate (5 %) was calculated for ultrasound (single NT or
      NT and NB), serum biochemistry, maternal age and the combination of these
      components. RESULTS: Pregnancy outcome was obtained in 2973 (93.6 %) cases. Nasal
      bone was absent in 5 of 18 (27.8 %) cases with fetal trisomy 21 and in 2 of 2961
      (0.1 %) normal cases. The estimated risks for trisomy 21 based on maternal age,
      fetal ultrasound and maternal serum free ss-hCG and PAPP-A was 1 in 300 or
      greater in (old algorithm without NB/new algorithm including NB) 5.5 % (179 of
      2961) and 2.8 % (97 of 2961) normal pregnancies and in 94.4 % (17 of 18) and 77.8
      % (14 of 18) of those with trisomy 21. For a fixed false-positive rate of 5 % the
      respective detection rates of screening for fetal Down's syndrome by maternal age
      and serum free ss-hCG and PAAP-A, maternal age and fetal ultrasound and by
      maternal age, fetal ultrasound and maternal serum biochemistry were (old
      algorithm without NB/new algorithm including NB) 72.2 %/66.7 %, 83.3 %/77.8 % and
      88.9 %/83.3 %, respectively. CONCLUSION: Our data show no additional performance
      of including presence or absence of fetal nasal bone in calculation of risk for
      fetal Down's syndrome between 11 and 14 weeks of gestation. Individual risk
      orientated two-stage screening could be an alternative approach for integration
      of additional ultrasound markers in first trimester screening.

PMID- 16596512
TI  - Changing attitudes towards non-invasive aneuploidy screening at advanced maternal
      age in a German tertiary care center.
AB  - OBJECTIVE: To evaluate attitudes towards non-invasive aneuploidy screening at
      advanced maternal age in a German tertiary care centre and to compare the rate of
      invasive testing over a period of four years. METHODS: A retrospective analysis
      of 2657 singleton pregnancies with targeted first and second trimester ultrasound
      examination at 11-14, 15-18 and 19-23 weeks' gestation. RESULTS: The number of
      patients at or beyond 35 years increased by 36 % over this period. Concomitant
      with an increasing proportion of first trimester examinations (+ 13 %), a
      decrease in 15-18 weeks' examinations (- 14 %), but no changes regarding the 19
      23 weeks' examination were observed. A total of 78 (2.9 %) abnormal karyotypes
      were found and 92 % (56/61) of the cases with autosomal trisomy had sonographic
      markers suggestive of foetal aneuploidy. The proportion of diagnosed chromosomal
      abnormalities at 11-14 weeks increased from 14 % in the first half to 49 % in the
      second half of the study period (p < 0.01). We observed a significant decrease in
      the rate of invasive procedures, especially in women reassured by a normal
      ultrasound examination (54 % versus 37 %, p < 0.01). CONCLUSION: There is an
      increasing acceptance of first trimester targeted ultrasound examination with the
      potential advantage of an earlier diagnosis of foetal aneuploidy. Furthermore, we
      observed annually increasing numbers of women who used the results of the
      ultrasound examination to guide their final decision about invasive testing,
      rather than undergo genetic testing as a primary option.

PMID- 16596514
TI  - Intrapericardial teratoma in the newborn--3D-echocardiography and course of
      disease.
AB  - Intrapericardial teratoma is a rare tumour which may become life threatening when
      it causes mediastinal compression. Early sonographic detection and careful
      evaluation is necessary for further management. In this paper, we present a case
      with a large intrapericardial teratoma diagnosed in utero (25 + 0 weeks). After
      birth, 3D-echocardiography was particularly helpful in obtaining a comprehensive
      view of the three-dimensional structure of this complex tumour, in order to
      determine tumour extension and attachment before surgical excision. This case
      illustrates the opportunities which new, noninvasive echocardiographic tools
      create to aid therapeutic management and surgical therapy of critically ill
      patients.

PMID- 16596513
TI  - Ultrasonographic findings in patients with olecranon bursitis.
AB  - BACKGROUND: Musculoskeletal ultrasonography (U.S.) is an important imaging
      technique in the diagnosis of olecranon bursitis, especially for early
      manifestation. It allows sensitive detection of small fluid collections as well
      as for differentiation between soft tissue and bone lesions. U.S. examination
      allows detection of effusions, synovial proliferation, calcifications, loose
      bodies, rheumatoid nodules, gout tophi and septic processes. AIM: To assess the
      role of ultrasonography in the diagnosis and management of patients with
      olecranon bursitis. METHODS: Ultrasound was used in 34 patients with swelling
      above the olecranon. The opposite asymptomatic side served as a control group.
      RESULTS: 20 patients demonstrated increased fluid collection in the olecranon
      bursa. 5 had synovial proliferation, 2 cases showed loose body, 5 patients
      revealed markedly increased blood flow consistent with inflammation, 2 patients
      had triceps tendonitis with calcifications. CONCLUSIONS: Sonography is an
      extremely effective tool for the diagnosis of soft tissue lesions in the
      olecranon area.

PMID- 16596515
TI  - Ultrasonography of the temporal, periorbital and carotid arteries in the
      diagnosis of giant cell arteritis and its neuroophthalmological complications.
AB  - AIM: Evaluation of the diagnostic contribution of colour duplex sonography of the
      superficial temporal and the carotid arteries and Doppler sonography of the
      periorbital arteries by analysing the results in patients with giant cell
      arteritis with and without neuroophthalmological complications and patients with
      other diagnoses and neuroophthalmological complications. METHODS: In a case
      control study, ultrasonographic findings in patients with neuroophthalmological
      complications (25 giant cell arteritis, 23 non giant cell arteritis) were
      compared to those of 62 patients suffering from giant cell arteritis without
      neuroophthalmological complications. Concentric hypoechogenic mural thickening (a
      so-called halo) was considered as an ultrasonographic finding typical of giant
      cell arteritis. Absent or retrograde signals not corresponding to carotid
      occlusive disease were classified as Doppler sonographic findings typical of
      giant cell arteritis of the periorbital arteries. RESULTS: There are higher rates
      of abnormalities in Doppler sonography of the periorbital arteries as well as
      halos in combination with stenosis of the temporal arteries in patients with
      giant cell arteritis with neuroophthalmological complications. This suggests that
      in patients with giant cell arteritis and neuroophthalmological complications,
      the haemodynamic situation is more severely disturbed. Patients suffering from
      giant cell arteritis with and without neuroophthalmological complications had the
      same rate of temporal artery abnormalities on colour duplex sonography (72 vs. 71
      %), whereas abnormalities in the periorbital arteries were clearly different (40
      vs. 8 %). Only 1 patient with giant cell arteritis without neuroophthalmological
      complication had anomalies of the carotid arteries typical of giant cell
      arteritis. In patients with other diagnoses and neuroophthalmological
      complications, the rate of anomalies in temporal artery colour duplex sonography
      and Doppler sonography of the periorbital arteries was 9 % and 0 %. CONCLUSION:
      Colour duplex sonography of the superficial temporal and carotid arteries and
      Doppler sonograpy of the periorbital arteries are complementary methods and
      should be part of the evaluation of all patients suspected to suffer from giant
      cell arteritis.

PMID- 16596516
TI  - Common bile duct wall thickening due to intramural varices diagnosed by colour
      Doppler ultrasound.
AB  - Cases of common bile duct (CBD) wall thickening due to varicose dilation of
      intramural veins consequential to portal vein thrombosis (PVT) are rare and
      present a considerable differential diagnostic problem, as they can mimic
      cholangiocarcinoma. In such cases, colour Doppler ultrasound (CD US) is a very
      valuable diagnostic method. There are only a few reports in literature on CD US
      findings of collateral circulation in a thickened CBD wall following PVT. A
      patient with obstructive jaundice, a tumour of the pancreatic head, CBD wall
      thickening, and pre-existing PVT is presented. CD US demonstrated collateral
      circulation of the thrombosed portal vein in the thickened wall of the common
      bile duct, thus ruling out a mass in the CBD. Obstructive jaundice seldom occurs
      with choledocal varices. In this patient, the bile duct obstruction was due to
      the carcinoma of the pancreatic head.

PMID- 16596517
TI  - Ultrasound-guided interscalene brachial plexus anaesthesia: differences in
      success between patients of normal and excessive weight.
AB  - Interscalene plexus blocks are an important part of the peri-operative treatment
      in shoulder surgery. The nerve stimulation technique uses external landmarks for
      the definition of the injection site. Patient obesity is, therefore, one
      causative factor for a reduced success rate of the blockade. AIM: This study
      investigated whether there are differences in visibility of the target nerves and
      in the success rate of the block between patients of normal weight (nw) and obese
      patients (ow), when portable sonography is used for guidance of the interscalene
      nerve blockade (ISB). METHODS: We investigated 70 patients routinely scheduled
      for shoulder surgery (ASA status I-III). The patients were allocated to group nw
      (body mass index BMI< 25) or ow (BMI > 25). The interscalene part of the brachial
      plexus was examined using high-frequency portable ultrasound. The blockade was
      performed under continuous sonographic monitoring. The quality of the ISB was
      tested post-operatively, and the time required for the procedure was documented.
      RESULTS: Identification of nerve structures in the obese patients did require
      slightly more time than in patients of normal weight, statistically (ow: 5 +/- 1
      min versus nw: 4 +/- 2 min, p = 0.02). While in 33 patients (94 %) of group nw
      the plexus blockade was complete, in group ow 27 (77 %) of the blocks were
      sufficient. The difference in success, however, was not significant (p = 0.08).
      Visualisation of nerves was difficult in 3 patients in ow-group. CONCLUSION:
      Portable ultrasound provides efficient depiction of the interscalene plexus
      structures in obese patients and, when used for guidance of regional blockade,
      renders similar results as in patients of normal weight.

PMID- 16596518
TI  - Morphological features of enlarged parathyroid glands in B-mode-ultrasound.
AB  - Successful preoperative localisation of parathyroid glands is essential for
      minimal-invasive surgery of hyperparathyroidism. The knowledge of the
      sonomorphology of the parathyroid glands, therefore, is an important
      prerequisite. This article shows that the sonomorphology of normal and
      pathologically transformed parathyroid glands is subject to a wide variety. The
      often simplified standard description of parathyroid glands as hypoechogenic and
      oval may lead to false negative cervical ultrasound examinations.

PMID- 16596519
TI  - [Ultrasound evaluation of the acromioclavicular joint--a correlation of
      anatomical and sonographical findings].
AB  - AIM: To compare ultrasound imaging to the anatomy of the acromioclavicular joint.
      METHODS: 13 cadaveric acromioclavicular joints were examined by ultrasound (11
      MHz linear array transducer) to determine the limits of the joint capsule and the
      width of the joint space. The results were compared to macroscopic sections.
      RESULTS: Anatomical variations were observed. The joint space of one specimen was
      completely filled by fibrous tissue, leaving 12 specimens for a complete study. A
      hypoechoic meniscoid disc was attached to the superior joint capsule, resulting
      in a convex curvature of the cranial part. The mean sonographic width of the
      joint space was 3.9 mm +/- 1.7 mm standard deviation (SD). The mean distance of
      the joint capsule from the articular bone rim of the clavicle, the acromion, and
      from the middle of the joint space was 1.1 +/- 1.0 mm, 1.3 +/- 0.7 mm, and 2.1 +/
      0.9 mm, respectively. The distance from the joint space to the capsular
      insertion on the clavicle and on the acromion was 4.4 +/- 1.4 mm and 5.3 +/- 2
      mm, respectively. The mean difference between ultrasound and anatomical
      measurements in the vertical (cranio-caudal) plane was 0.5 +/- 0.5 mm (SD),
      whereas the mean difference between measurements in the horinzontal (medio
      lateral) plane was 1.3 +/- 1.1 mm (SD). CONCLUSION: Due to low cost, safety and
      wide availability, sonography is suited for the evaluation of the
      acromioclavicular joint. However, when interpreting the results, errors in
      measuring, limitations in resolution of the system used, and the anatomy of the
      acromioclavicular joint and its anatomical variants have to be taken into
      consideration.

PMID- 16596520
TI  - [The value of highest quality ultrasound as a reference for ultrasound
      diagnosis].
AB  - AIM: The aim of this study is to determine whether an additional ultrasound
      examination of DEGUM grade 3 (DEGUM 3) requested by examiners of DEGUM grade 1, 2
      (DEGUM 1, 2) results in a diagnostic improvement. METHODS: From October 2000 till
      June 2003 our university internal medicine sonography unit examined 34 980
      patients. In 211 cases DEGUM grade 1, 2 examiners requested a second opinion by
      DEGUM grade 3 examiners. 28 subjects were excluded because of unconfirmed
      diagnosis. Data of 183 patients with assured diagnoses were retrospectively
      analysed. We compared DEGUM 1, 2 findings with DEGUM 3 results regarding the
      accuracy of the firmed diagnosis. RESULTS: In 38.8 % (71 out of 183 subjects) the
      correct diagnosis was ascertained by DEGUM 1, 2. DEGUM 3 confirmed the correct
      diagnosis in 94.5 % (173 out of 183 subjects). DEGUM 3 changed 106 (57.9 %)
      findings of DEGUM 1, 2 and approved 77 findings (42.1 %). In total DEGUM 3
      diagnosed incorrectly twice compared to DEGUM 1, 2. In comparison to the assured
      diagnosis DEGUM 3 diagnosed 10 subjects incorrectly. CONCLUSION: The reference
      ultrasound examination done by an examiner with DEGUM grade 3 significantly
      increases the diagnostic accuracy compared to the ultrasonic measurement done by
      DEGUM grade 1, 2 investigators.

PMID- 16596522
TI  - Needle stick injuries: how can we minimise our risk?
AB  - In the United Kingdom (UK) there is inequity in health care workers access to
      safer sharps and needle free systems. The availability of safer sharps and needle
      free systems is dependent on the budget manager authorising the purchase of these
      devices within individual hospitals. This can mean that within the same
      organisation one department can be using safer sharps and needle free systems,
      while another department is denied access to such equipment. This is partly due
      to competing priorities for scarce health care resources, which is becoming more
      acute, and lack of national guidance to employers to provide such safety
      equipment for their employees. At the current time the UK does not have a
      mandatory reporting system for sharps injuries, so the true extend of the problem
      is not fully understood.

PMID- 16596523
TI  - How to avoid and manage a pneumothorax.
AB  - Pneumothorax is one of the most frequent complications during percutaneous
      central vascular cannulation. When choosing a site for central vascular access,
      the internal jugular vein is preferable to other vessels, for the lower frequency
      of related complications, including pneumothorax. This review intends to
      summarize the current state of the art on how to avoid and, if it occurs, to
      manage this rare but relevant complication. In order to prevent pneumothorax, as
      well as other relevant complications of central vein cannulation, it is advisable
      to use ultrasound guidance whenever possible. If pneumothorax occurs, it is
      important to recognize its signs and symptoms. To exclude the presence of
      asymptomatic pneumothorax, in the normal clinical routine a chest X-ray should be
      obtained within 4 hours from the procedure of central vein cannulation of
      subclavian and internal jugular veins. If promptly recognized, pneumothorax can
      be managed quickly and in a relatively easy way. Depending on its size and
      symptoms, and in particular when a tension pneumothorax is suspected, treatment
      can vary from simple observation to a chest tube insertion or, in the latter
      case, to an emergency thoracentesis needle insertion in the pleural space.

PMID- 16596524
TI  - Blood flow study of arteriovenous grafts with homologous and autologous veins in
      canine femoral vessels.
AB  - PURPOSE: The objective of this study was to assess the blood flow in
      arteriovenous (AV) communications comparing autologous and homologous veins, in
      the femoral vessels of dogs. METHODS: Ten mongrel dogs were used for the blood
      flow analysis, and two AV grafts (AVG) were placed in each of them. The grafts
      were made with an autologous vein in one side, and a omologous vein, kept in a
      0.25% glutaraldehyde solution, in the other side. The volumetric flow was
      measured before and after AVG placement. Fifteen minutes after surgery, the
      volumetric flow was measured in the cranial artery, in the caudal artery, in the
      graft and in the vein, and the same procedure was repeated 15 days after surgery.
      Measurements were done using an eletromagnetic flowmeter calibrated previously.
      For data analysis, the Wilcoxon test was used (to compare the difference in the
      results between the times and the techniques used) alfa </=0.05). RESULTS: An
      increase of about 5.3 times was observed in the femoral artery cranial portion
      flow of these accesses during the first operation and an increase of 6.8 times in
      the re-operation for both techniques. In the femoral artery caudal portion of the
      AVGs there was a blood flow inversion of about 1.6 times for both techniques
      during the first operation and about 4.1 and 3.7 times for the autologous and
      homologous veins, respectively. There was a significant increase in the
      autologous grafts. In the cranial portion of the femoral vein, there was an
      increase in the flow in relation to the femoral artery flow before graft
      placement. There was an increase of 5.3 and 7.4 times for the autologous and
      homologous grafts, respectively, in the first operation and from 8-9.6 times in
      the re-operation. There was also a significant increase in the autologous graft
      in relation to the two procedures. A significant difference among the grafts
      placed during the first surgery was observed, which was not observed after 15
      days. In the graft blood flow analysis, a flow increase of 5.1 times for the
      autologous vein and 6.6 times for the homologous vein and from 7.5-8.2 times in
      the re-operation was found in relation to the femoral artery flow. There was a
      significant increase in autologous vein flow between the first operation and the
      re-operation. CONCLUSION: The mean blood flow of the homologous AVG was greater
      during the first operation and similar to the autologous grafts during the re
      operation. Therefore, the homologous AVG could be considered a possible
      alternative to vascular access for hemodialysis.

PMID- 16596525
TI  - Infection assessment of totally implanted long-term venous access devices.
AB  - AIM: Comparison of catheter tip versus port content culture techniques to assess
      infection in totally implanted vascular access devices (TIVAD). MATERIALS AND
      METHODS: Comparison of pocket swab, catheter-tip and port content cultures after
      removing the silicon puncture septum in a prospectively collected consecutive
      series of 102 TIVAD removed for clinical suspicion of infection, between May 2000
      and March 2003. RESULTS: 102 totally implanted port-catheters in 98 patients, age
      ranging from 1 to 90 years (median 53 years), were removed 7 to 2616 days after
      insertion (median 210 days). Infection of the pocket surrounding the port was
      found in 21 cases, all proven by a positive culture of the pocket swab. Out of
      the remaining 81 cases without pocket infection, 32 had only a positive catheter
      tip culture, whereas 56 had a positive port content culture (p = 0.0002). Always
      the same microorganism was isolated in the 32 patients with positive catheter tip
      and port content cultures. The main organisms identified within TIVAD were
      Coagulase Negative Staphylococcus (CNS) (41 cases) and Candida sp (15 cases).
      Eight out of the 21 pocket infections were caused by Staphylococcus aureus.
      CONCLUSION: In the presence of local signs of infection, taking cultures of the
      pocket surrounding the port is sufficient for diagnostic purposes. When infection
      is localized within the device only, port content cultures taken after removal of
      the silicon septum are more often positive than cultures of the catheter tip, and
      constitute therefore a more reliable tool for the assessment of TIVAD infection.

PMID- 16596526
TI  - Functional vascular access evaluation after elective intervention for stenosis.
AB  - PURPOSE: To evaluate the functional effects of preventive vascular access (VA)
      intervention through periodic blood flow (Q A ) measurements during hemodialysis
      (HD) by the delta-H method. METHODS: We prospectively monitored the blood flow
      rate (Q A ) of 100 VA (arteriovenous fistula (AVF) 81% or AV graft (AVG) 19%;
      mean VA duration 24.6 +/- 42.3 months) during HD in 89 end-stage renal disease
      patients (mean age 62.7 +/- 13.6 yrs; mean time on HD 30.9 +/- 43.9 months; 18%
      with diabetes) over a 3-yr period. Q A was measured at least every 4 months by
      the delta-H method (Yarar (6)) using the Crit Line III Monitor (overall mean Q A
      1247.6 +/- 519.7 ml/min). The mean arterial pressure (MAP) and Kt/V index were
      measured simultaneously with Q A . Thirty-eight VA (38%) met the positive
      evaluation criteria (absolute Q A <700 ml/min 50%, Q A decreased >20% from
      baseline 50%). Most cases with positive evaluation underwent angiography (36/38,
      95%) and had stenosis >/=50% (34/36, 94%). Of VA with significant stenosis, 17
      (17/34, 50%) VA (AVF 76.5%, AVG 23.5%; mean VA duration 12.5 +/- 22.4 months,
      mean percentage of VA stenosis 75.8%) in 15 patients (mean age 68.4 +/- 9.8 yrs;
      mean time on HD 14.2 +/- 18.2 months; 33.3% with diabetes) underwent corrective
      intervention by angioplasty, 35.3% (6/17), and revision surgery, 64.7% (11/17).
      RESULTS: Short-term results: Elective intervention was successful in 88% of
      treated VA (15/17). Mean Q A increased from 563.8 +/- 115.4 ml/min just before
      intervention (Q A pre) to 975.7 +/- 351.8 ml/min just after intervention (Q A
      post) (mean delta Q A = 411.8 +/- 290.1 ml/min) (p < 0.001). We found a
      significant difference between the overall mean Q A before (689.6 +/- 227.0
      ml/min) vs after intervention (965.9 +/- 396.8 ml/min) (p = 0.011). No difference
      was found when the highest recorded mean Q A before intervention (877.7 +/- 415.4
      ml/min) and mean Q A post were compared (p = 0.25). Mean MAP did not change after
      intervention (91.5 +/- 12.5 vs 92.7 +/- 14.2 mmHg, p = 0.46). Mean Kt/V index
      improved from 1.44 +/- 0.24 just before intervention to 1.49 +/- 0.23 just after
      intervention without any change in dialyzer type or HD duration (p = 0.025). Mean
      delta Q A was similar for diabetic patients vs non-diabetic patients (p = 0.34),
      for younger patients (age <65 yrs) vs older patients (age >/=65 yrs) (p = 0.64)
      and for AVF vs AVG (p = 0.39). We found a positive correlation between mean delta
      Q A and mean Q A post (r = 0.95, p < 0.001) or between mean delta Q A and overall
      mean Q A after intervention (r = 0.77, p < 0.001). Long-term results: Prevalence
      of VA thrombosis during the follow-up period (354.4 +/- 293.1 days): 17.6%
      (3/17). Five (29.4%) treated VA showed restenosis and two of them (40%) underwent
      reintervention by surgery. Mean restenosis period and mean decrease in Q A were
      232.6 +/- 74.1 days and 2.8 +/- 0.6 ml/min/day, respectively. No significant
      correlation was found between mean delta Q A or Q A pre and mean restenosis
      period or decrease in Q A (p = ns). CONCLUSIONS: 1) Monitoring Q A by the delta-H
      method is useful in assessing the hemodynamic response to elective VA
      intervention. 2) Mean Q A post was similar to the highest recorded mean Q A
      before intervention. 3) Mean delta Q A was related to mean Q A post and overall
      mean Q A after intervention. 4) The HD effectiveness (Kt/V index) improved after
      intervention.

PMID- 16596527
TI  - Collateralization of the palmar arch by a failing radiocephalic fistula: an
      underappreciated complication of Cimino fistula anatomy.
AB  - Stenosis at the anastomosis of an arteriovenous dialysis fistula can cause
      fistula failure due to venous thrombosis. Three cases are presented in which
      anastomotic stenosis in radiocephalic fistulas resulted in radial artery
      occlusion with collateralization of ulnar artery flow across the palmar arch.
      Hand ischemia did not occur, and reductions in fistula efficiency were clinically
      subtle. Urea kinetics were compromised, and a characteristic palmar bruit was
      heard.

PMID- 16596528
TI  - Ultrasound guided brachial arterial angioplasty during the creation of a radio
      cephalic arteriovenous fistula: a case report.
AB  - To prevent arteriovenous fistula (AVF) early failure, due to radial or brachial
      artery stenosis, ultrasound guided angioplasty performed while surgically
      creating the AVF could be an effective procedure. CASE REPORT: A 76-year-old
      diabetic male patient, on hemodialysis (HD) for 15 months, presented extensive
      thrombosis of the radio-cephalic AVF at the right arm, which had lasted for about
      10 days. Ultrasound examination showed a 40% brachial artery stenosis with
      eccentric calcified plaque. The stenosis was localized about 1.5 cm before the
      artery bifurcation. The brachial artery diameter was 0.45 cm before and 0.26 cm
      at the level of the stenosis, the latter being 0.45 cm long. At the left wrist,
      under local anesthesia, the radial artery and the cephalic vein were exposed; the
      radial artery was then longitudinally incised for 7-8 mm in the area selected to
      create the AVF. A 6 Fr introducer, a metallic guide wire and a catheter for
      angioplasty were inserted one after the other in the radial artery. When the
      correct position of the angioplasty catheter in the stenotic area was established
      by ultrasound examination, the balloon was blown up to 13 atm for 35 sec,
      reducing the stenosis from 40-20%. Finally, a side-to-side radio-cephalic fistula
      was created, legating the distal vein. The AVF was used for HD after 3 weeks. The
      follow-up at 6 months demonstrated fair access performance and it was used
      without problems. Our satisfactory experience suggests that ultrasound guided
      angioplasty of brachial artery stenosis, performed simultaneously with surgical
      AVF creation, is possibly a successful procedure. This technique reduces the risk
      of early AVF failure and also allows, when required, stent implantation.

PMID- 16596530
TI  - Vasculorama.

PMID- 16596531
TI  - Emerging role of Enterococcus spp in catheter-related infections: biofilm
      formation and novel mechanisms of antibiotic resistance.
AB  - Enterococci are gram-positive bacteria that are part of the normal human
      intestinal flora and can colonize the upper respiratory tract, biliary tract and
      vagina of otherwise healthy people. Although their virulence is relatively low,
      recently enterococci have emerged as significant nosocomial pathogens and are
      currently the 4th leading cause of hospital-acquired infections, including those
      associated with intravascular catheter and biliary stent implants. The frequent
      use of these medical devices is often associated with severe complications,
      including catheter-related bloodstream infections (CRBSIs) and biliary stent
      occlusions, because of microbial biofilm formation on the device surface.
      Furthermore, other than a high level of resistance to penicillin, ampicillin and
      aminoglycosides, a dramatic increase in vancomycin resistance of enterococci has
      been recently observed in most clinical settings. Clinical strains exhibiting
      novel mechanisms of acquired resistance to antimicrobials are frequently
      isolated. In addition, enterococci have a great ability to transmit these
      resistance traits to other species and even to other genera. Due to their
      associated morbidity and mortality, enterococcal infections related to medical
      devices currently represent a major challenge for clinicians, especially for the
      management of critically ill patients, resulting in prolonged hospitalization and
      additional health costs.

PMID- 16596529
TI  - Azygos arch cannulation by central venous catheters for hemodialysis.
AB  - Cannulation of central veins and placement of catheters for temporary
      haemodialysis is a common procedure in the management of patients with end stage
      renal failure. The internal jugular vein is the site of choice for central venous
      catheter placement, being associated with the lowest complication rate. This
      procedure can be associated with a variety of malpositions of the catheter and
      rarely, can lead to significant morbidity and even mortality, if this is not
      recognised and corrected early. For anatomical reasons, the risk of azygos arch
      cannulation is substantially increased if catheters are inserted via left-sided
      veins. We report a case with a rare complication associated with the insertion of
      a catheter for temporary haemodialysis.

PMID- 16596532
TI  - Old and new tools in the diagnosis of central venous catheter-related bloodstream
      infections: is there a role for brushing?
AB  - Bloodstream infections (BSIs) are the third most common nosocomial infections.
      Catheters and other medical devices are the first exogenous causes of preventable
      infections in hospital. The estimated attributable mortality for catheter
      associated BSI ranges from 1-35%, mainly depending on etiological agents and
      underlying disease. In considering this, it is necessary to reduce central venous
      catheter- (CVC)-related BSI prevalence and to obtain a rapid and accurate method
      for an early diagnosis. This review indicates the advantages and the
      disadvantages of old and new tools for the early diagnosis of CVC-related BSIs.

PMID- 16596533
TI  - Steal syndrome after brachiocephalic fistula for vascular access: correction with
      a new simple surgical technique.
AB  - PURPOSE: Steal syndrome is the condition of arterial insufficiency distal to a
      permanent haemodialysis fistula. Three treatment options have been recommended:
      ligation of the fistula, banding of the fistula, and distal revascularization. We
      report an alternative simple surgical technique for correction of steal syndrome.
      METHODS: Two patients were treated for steal syndrome after brachiocephalic
      fistula operation. The treatment of the steal syndrome was done by interponating
      an ePTFE graft loop tunnelated subcutaneously in the upper arm. RESULTS: At
      follow-up one year later both fistula were patent without any reoperation and
      with normal flow at haemodialysis. There were no symptoms of steal. CONCLUSION:
      This new method for correction of steal syndrome seems to be an attractive
      alternative.

PMID- 16596534
TI  - ProCol vascular bioprosthesis for vascular access: midterm results.
AB  - BACKGROUND/AIMS: This study aimed to evaluate the safety and efficacy of the
      ProCol vascular bioprostheses as vascular access (VA) material, especially in
      patients with a history of prior failed access. METHODS: During a 20-month
      period, 25 arteriovenous (AV) bovine vein grafts were placed in 24 hemodialysis
      (HD) patients for VA. All patients presented with failed autologous access sites.
      RESULTS: Graft placement was successful in all patients with no procedure-related
      complications. Follow-up from 6-26 months gave primary 6-month, 12-month and 24
      month patency rates of, respectively, 90%, 80% and 70%. Graft characteristics in
      cannulation and hemostasis were very satisfying. CONCLUSION: Our midterm results
      demonstrated that the ProCol vascular bioprosthesis was a promising material for
      VA with good patency and low complication rates.

PMID- 16596535
TI  - New graft for low friction tunneling in vascular access surgery.
AB  - PURPOSE: Prosthetic accesses of the upper extremity have been in use for more
      than 25 years. Many different conduits have been employed; investigators have
      continually searched for a graft with superior properties. METHODS: We describe a
      prospective randomized study comparing the new Slider Graft (Atrium) with the
      Hybrid PTFE Graft (Atrium); the latter has been used for a number of years. The
      Slider Graft is also made of PTFE. For this study, both grafts were 6 mm in
      diameter and 40 cm in length. The Slider Graft has a low friction polyethylene
      sheath over its entire length. This sheath expedites the passage of the graft
      through the tunnel. At one end, the graft and the polyethylene sheath are
      attached to a metal tip. This tip has male threads, which may be inserted firmly
      into a Kelly Wyck, Atrium, or any standard non-sheath tunneling system. This
      alleviates graft separation, turning, and slipping during tunneling. The primary
      objective of this trial was to determine the safety and efficacy of the Slider
      Graft as compared to the Hybrid Graft in vascular access surgery. The secondary
      objective was to evaluate how tunneling effects graft performance. We randomized
      60 subjects for this study with two equal arms. During surgery we measured
      various parameters including ease of tunneling, tunnel bleeding, anastomotic
      bleeding, graft sweating, and immediate patency. To assess arm edema we measured
      circumference 7.5 cm and 20 cm above the wrist, prior to surgery and in follow-up
      visits at 1 week, 1 month, and 3 months. Primary patency was also assessed at
      these visits and at 6, 9, and 12 months. RESULTS: Our results show tunneling with
      the Slider Graft is easier to accomplish (p = 0.0001) with reduced tunnel
      bleeding (p = 0.0047) and anastomotic bleeding (p = 0.042). Further, the Slider
      Graft virtually eliminated the complication of graft sweating and seroma
      development (p = 0.0005). This may be due to reduced stretching and graft wetting
      during insertion. At 180 days the Slider Graft demonstrated improved primary
      patency, which was statistically significant (p = 0.047). At 360 and 720 days the
      Slider Graft continued to demonstrate a trend toward improved primary patency (p
      = 0.160). CONCLUSIONS: This study suggests the Slider Graft has significant
      advantages when compared to the Hybrid Graft and highlights the importance of
      tunneling in creating prosthetic accesses.

PMID- 16596536
TI  - Comparison of different techniques of hemodialysis vascular access flow
      evaluation.
AB  - Measurement of vascular access flow (QVA) has been suggested as a method of
      choice for vascular access quality (VAQ) monitoring. Besides traditional duplex
      Doppler, a number of bedside methods based mostly on the Krivitski principle of
      QVA evaluation from recirculation at reversed needles (RX), have been developed.
      This work compares ultrasonic dilution (UD), taken as a reference, HD01,
      Transonic Systems; duplex Doppler (DD); thermodilution (TD), BTM, Fresenius;
      optodilutional RX measurement (ORX), Critline III, R-mode, HemaMetrics; direct
      optodilutional QVA evaluation from jumpwise changes in ultrafiltration rate at
      both normal and reversed needles connection (OABF), Critline III, ABF-mode; and
      direct transcutaneous optodilutional QVA evaluation (TQA), Critline III TQA.
      Firstly, reproducibility of each method was assessed by duplicate measurement at
      unchanged conditions. This was followed by paired measurement with each method
      performed at controlled change in relevant measurement condition (two different
      extracorporeal blood flows in UD and TD, changed sensor position in TQA). Finally
      paired measurements by each method and the reference method performed at
      identical conditions were evaluated to assess accuracy of each method. The simple
      Krivitski formula QVA= QB(1-RX)/RX was used wherever manual QVA calculation was
      needed. Very high reproducibility was seen in UD, both for measurement at the
      same extra corporeal blood flow (QB) (correlation coefficient of duplicate
      measurement r= 0.9702, n= 58) and for measurement at two different QB (r= 0.9735,
      n= 24), justifying its current status of a reference method in QVA evaluation.
      Slightly lower reproducibility of TD measurement at the same QB (r= 0.9197, n=
      40) and at two different QB (r= 0.8508, n= 168) can be easily overcome by
      duplicate measurement with averaging. High correlation of TD vs. UD (r= 0.9543,
      n= 54) makes TD a viable clinical alternative in QVA evaluation. Consistently
      different QVA obtained at two different QB should prompt closer investigation of
      anatomical conditions of the access. Use of the simple Krivitski formula in TD
      (which measures total recirculation, i.e. sum of access recirculation and
      cardiopulmonary recirculation) brings about underestimation of QVA, which
      progressively increases from QVA of about 600 ml/min up. Good correlation,
      although with significant scatter (r= 0.8691, n= 27) was found between the DD-
      and UD-based QVA. By far the worst reproducibility at the same QB from among the
      investigated methods was found in ORX (0.6430, n= 23). Also the correlation of
      ORX vs. UD was lower than in other methods (r= 0.702, n=33) and general
      overestimation of QVA by about 25% was noted. Correlation of OABF vs. UD (r=
      0.6957, n= 26) was slightly better than that of ORX and it gave less
      overestimated values. The TQA method showed very high reproducibility (r= 0.9712,
      n= 85), however only for unchanged sensor position. Correlation of QVA measured
      at two different sensor positions was much worse (r= 0.7255, n= 22).
      Correspondence of TQA vs. UD was satisfactory (r= 0.8077, n= 36). Skilled and
      experienced operators are a must with this method.

PMID- 16596537
TI  - Bridge graft to a small distal artery after fistula ligation for angioaccess
      induced ischemia: report of two cases.
AB  - Angioaccess-induced ischemia is an infrequent but cumbersome problem, because
      both limb ischemia correction and access salvage should be undertaken during the
      same procedure. This paper reports two cases that we successfully managed with a
      bridge graft to a small distal artery after fistula ligation.

PMID- 16596538
TI  - Secondary migration of a central venous catheter: a rare complication.
AB  - The Authors describe a case of spontaneous migration in the right jugular vein of
      a central venous catheter tip, properly positioned in the right atrium through
      the right subclavian vein two days before.

PMID- 16596539
TI  - Early rupture of subclavian vein catheter: a case report and literature review.
AB  - Prolonged venous access devices (PVADs) have become indispensable in antiblastic
      protocols for the treatment of cancer patients, in anti-infection protocols for
      acquired immunodeficiency syndrome (AIDS) patients and in the management of
      chronic malabsorption syndromes. Using these catheters carries the risk of
      several complications, and some are potentially lethal, for example, cardiac
      embolization of catheter fragments. Rupture is a complication almost exclusive to
      catheters positioned percutaneously: after using this technique, device
      malfunction can occur due to catheter kinking after its excessively medial
      introduction in the subclavian vein. The early recognition of any pinch-off sign
      (POS) is fundamental in preventing catheter rupture that frequently follows this
      complication. Other factors can be involved in early rupture, for example,
      excessive force on a syringe used to clear a catheter that shows early signs of
      malfunction, or a strength defect in the materials used in the catheter
      construction. This report describes an early rupture case of an initially
      correctly positioned catheter and reviews 20 such cases in the recent literature.

PMID- 16596540
TI  - Vasculorama.

PMID- 16596541
TI  - Salvage insertion of tunneled central venous catheters in the internal jugular
      vein after accidental catheter removal.
AB  - PURPOSE: Tunneled catheters are widely used for intermediate to long-term
      hemodialysis (HD) access, but are prone to several complications that can require
      catheter replacement. Replacing malfunctioning catheters with a new line, placed
      in a different access site, can lead to problems with multiple vein occlusions.
      This has led many nephrologists to continue using the same vein as long as
      possible by guidewire catheter exchanges, to preserve other veins for future use.
      We describe a guidewire exchange technique for the Ash-Split catheter in the
      internal jugular vein. METHODS: In three patients, the exchange was performed
      because of partial catheter removal, as evidenced by the outward dislocation of
      the Dacron cuff. In these patients, the guidewire was inserted through the
      catheter. In two additional patients, the catheter had been completely removed by
      accident: the replacement of the dislodged tunneled venous catheters was
      attempted 5 hr and 1 day after accidental removal. In these patients, the
      guidewire was inserted through the previous tunnel. After guidewire placement, a
      skin incision was made in the supraclavicular region. The metal guidewire was
      easily located inside the fibrous structure that had previously surrounded the
      catheter. The guidewire was then extracted from the subcutaneous tunnel and used
      to insert a new catheter safely and easily after creating a new tunnel. Patients
      were routinely given antibiotic prophylaxis (1 g of cefazolin) immediately before
      the procedure. A strict aseptic technique was used, including several sterile
      glove changes. RESULTS: No infections developed following this procedure, which
      has the potential for bacterial contamination. All procedures were successful.
      Only in one patient did we have to convert to a different catheter: it was not
      possible to replace the old Ash-Split catheter with the same dual-lumen catheter
      because of difficulties in inserting the peel away introducer-catheter complex.
      In this patient, rather than forcing it with larger dilators or trying to disrupt
      the fibrin sheath with balloon dilatation, a single lumen Tesio catheter was
      successfully placed. In both patients who completely lost the previous catheter,
      the guidewire was readily reinserted through the subcutaneous tunnel into the
      vein. Catheter function was excellent in all patients, with a test blood flow
      rate on the 1st catheter use >350 ml/min. CONCLUSIONS: We described a new method
      for catheter exchange, which allows the easy insertion of a new catheter and the
      creation of a new and safer subcutaneous tunnel. In addition, we demonstrated
      that in cases of complete catheter removal, it is possible to reinsert a catheter
      in the same vein through a guidewire, even when reinsertion was attempted up to 1
      day later.

PMID- 16596542
TI  - The role of surveillance in mature arteriovenous fistula management.
AB  - The existing guidelines recommend arteriovenous fistulae (AVF) surveillance by
      access blood flow (Qa) measurement and the correction of hemodynamically
      significant stenoses to prolong access survival. Unfortunately, many studies
      supporting these recommendations are inadequate methodologically; therefore, both
      the optimal criteria for surveillance and the value of preventive stenosis repair
      in AVF remain controversial. Recent literature confirms that Qa measurement
      allows an accurate identification of both stenosis (area under the curve (AUC)
      ranging from 0.80-0.93) and access at risk of failure (AUC ranging from 0.82
      0.98) in AVFs and suggests a Qa <700-1000 ml/min and/or a reduction in Qa >25% as
      optimal predictors for stenosis and a Qa <400 ml/min for incipient thrombosis.
      Recent prospective studies evaluated whether Qa surveillance could improve AVF
      patency rates compared to monitoring based on clinical and dialysis-related
      criteria alone. The majority of studies have historical, rather than concurrent,
      control groups and provide conflicting results, some showing a reduction and some
      showing no change in thrombosis rates by Qa monitoring. On the other hand, the
      few randomized controlled studies available show that Qa surveillance, when
      coupled with preemptive intervention, reduces the already low thrombosis rate in
      AVF and suggest that the functional access life can be prolonged. However, there
      is still the need for additional methodologically adequate studies to understand
      fully the role of surveillance in AVF management.

PMID- 16596544
TI  - Transparent film for intravascular catheter exit-site dressings.
AB  - Transparent polyurethane film is recommended for catheter site insertion dressing
      by the American guidelines for the prevention of infections associated with
      intravascular catheters. It has been proven to offer the advantages of excellent
      adhesion, firm support of the catheter, good tolerability, ease of application
      and fewer replacements per catheter lifetime. The last two features save nursing
      time and result in healthcare cost savings.

PMID- 16596543
TI  - Steal syndrome of the hemodialysis vascular access: diagnosis and treatment.
AB  - PURPOSE: Steal syndrome is an uncommon but serious condition of arterial
      insufficiency distal to a permanent hemodialysis fistula. The management of the
      condition is a great challenge to the surgeon because of the conflicting goals of
      preserving the fistula and treat the ischemia. In this review the purpose was to
      analyze the clinical problem and treatment possibilities. METHODS: Medline and
      Embase databases were searched for studies relevant to diagnosis and management
      of steal syndrome of the hemodialysis vascular access. RESULTS: The diagnosis of
      steal syndrome is largely based on clinical features and non-invasive studies. In
      same cases angiography may be necessary to find out the real causes of the steal
      syndrome. The cause is usually high fistula flow but other causes as steal
      phenomenon, inflow, outflow or anastomotic stenosis have to be considered and
      even combination of causes. The main treatment options are some form of flow
      reducing procedure or the distal revascularization interval ligation method. In
      some cases simple distal arterial ligation is the method of choice. Furthermore,
      in some patients a stenosis has to be treated as the first treatment option.
      CONCLUSIONS: For an appropriate treatment of a steal syndrome a careful analysis
      of the cause is important.

PMID- 16596545
TI  - Evaluation of vascular access complications in acute and chronic hemodialysis.
AB  - PURPOSE: This work aimed to determine the incidence of vascular access (VA)
      related complications of temporary venous catheters in acute hemodialysis (HD)
      prescription, to study the survival rate of chronic HD patients who began HD with
      a catheter insertion and to evaluate associated complications. METHODS: The
      patients were classified into two groups. Group I, patients in whom venous
      catheters were inserted (652 patients). Group II, 80 patients with end-stage
      renal disease (ESRD) in whom an arteriovenous fistula (AVF) was established.
      RESULTS: Complications in the femoral approach were bleeding from a femoral
      artery wall laceration in only 6/600 patients (1%), successfully repaired in all
      patients, bleeding from a punctured femoral artery in 30 patients (5%), the
      incidence of infection and removal was 40%. Other complications included groin
      hematoma in 3 patients (0.5%) and catheter thrombosis in 45 patients (7.5%). In
      the jugular vein approach, infection occurred in 6/30 patients (20%), thrombosis
      in 9 patients (30%), and accidental withdrawal in 2 patients (6.7%). In the
      subclavian vein approach, catheter dysfunction was found in 7/22 patients (32%),
      infection in 10 patients (45.5%), and failure to cannulate the vein in 3 patients
      (13.6%). In group II, limb edema was found in 14/80 patients (17.5%), hematoma in
      5 patients (6.3%), accidental trauma to the fistula in 2 patients (2.5%) and
      fistula stenosis in 15 patients (18.8%). Patients who began HD with a catheter
      had higher mortality than those who began with an AVF (12 months survival,
      respectively, 60 vs. 83%). CONCLUSION: Patients who began HD with a catheter had
      more complications and higher mortality. Routine quality assessment of AVF by
      Doppler ultrasound is recommended.

PMID- 16596546
TI  - Thrombotic events of arteriovenous fistulae in hemodialysis patients related to
      the C677T thermolabile variant of methylenetetrahydrofolate reductase.
AB  - BACKGROUND: Hyperhomocysteinemia is a risk factor for thrombosis, a frequent
      complication of vascular access (VA) in hemodialysis (HD). The enzyme
      methylenetetrahydrofolate reductase (MTHFR) is necessary for the remethylation of
      homocysteine (Hcy) to methionine. It has been postulated that patients homozygous
      and, to a lesser extent, heterozygous for the C677T thermolabile variant of this
      enzyme present a reduced catalytic activity, with secondary increases in
      plasmatic Hcy levels (normal: 10 +/- 5 micromol/L) and an elevated risk of
      vascular thromboses. METHODS: Sixty-two patients on chronic HD were divided into
      two groups: group A (n = 23, 37.1%) was normal for the enzyme (CC); group B (n =
      39, 62.9%) was heterozygous (CT). Both groups were not different according to
      age, sex, time on HD, hematocrits (Hct), baseline levels of Hcy, folic acid and
      vitamin B12. After the 1st HD session patients were started on folic acid 10
      mg/day and 500 microg/week of intravenous (i.v.) methylcobalamin. RESULTS: Two
      years later, thrombotic events were not different between the two groups. Group A
      = 5 (21.7%) vs. group B = 12 (30.7%), Hcy levels were significantly different
      between final and baseline measurements (group A 21.5 +/- 5.2 vs. 16.6 +/- 3.9
      micromol/L, p = 0.02; group B 22.1 +/- 8.9 vs. 16.1 +/- 3.9 micromol/L, p =
      0.008), folic acid (group A 22.1 vs. 346.9 ng/ml, range (r) =166-527, p < 0.001;
      group B 19.2 vs. 218.5 ng/ml, r = 138-298, p < 0.001) and vitamin B12 (group A
      1489 vs. 3192.3 pg/ml, r = 1494-4890, p = 0.01; group B 1086 vs. 1513.8 pg/ml, r
      = 1092-1934, p = 0.02). CONCLUSIONS: HD patients heterozygous for the C677T
      variant of the enzyme MTHFR can present a similar risk of thrombotic events in
      arteriovenous fistulae (AVF) compared to patients normal for the enzyme at a 1-yr
      follow-up. These results could be explained by an adequate control of Hcy levels
      after folic acid and methylcobalamin replacement therapy.

PMID- 16596547
TI  - Vasculorama.

PMID- 16596548
TI  - Stretch expanded polytetrafluoroethylene graft with intrawall radial support
      system: an advance in vascular access graft design.
AB  - Vascular access expanded polytetrafluoroethylene (ePTFE) grafts with external
      support systems consisting of parallel rings or in a spiral configuration are
      designed to resist kinking and compression at the apex of loop grafts or when
      crossing a joint. However, during the implantation procedure, the rings or spiral
      must be removed from the portion of the graft that is cut to allow the graft to
      be divided at the desired angle and suture the anastomosis. A new ePTFE graft
      (Intering) with an intrawall radial support system and a smooth lumen permits
      easy division of the support segments at the chosen angle. Moreover, minimal
      resistance is encountered during suturing of the graft. The results of early
      experience with Intering grafts crossing the elbow joint, in short-segment
      revisions, and in primary forearm loop configurations are encouraging.

PMID- 16596549
TI  - Treatment of dialysis catheter infections in 2004.
AB  - Hemodialysis catheter associated infections are a major source of morbidity and
      mortality in end stage renal disease patients. There is disagreement about the
      management of catheter infections, particularly concerning the removal of
      potentially infected tunneled dialysis catheters. A dialysis catheter should
      generally be removed when an infection involves a temporary hemodialysis
      catheter, a septic patient, a patient with a tunnel tract infection, or a patient
      with evidence of a metastatic infectious complication. In treating stable
      patients with clinically mild catheter associated bacteremia, parenteral
      antibiotics alone have a low success rate in eliminating the infection.
      Antibiotic locks are an emerging strategy for treating these patients, but at
      present higher rates of success and lower costs are achieved by exchanging the
      catheter over a guidewire. Antibiotic lock solutions, antibiotic coated
      catheters, and totally implantable dialysis access systems may play a large role
      in prevention of catheter associated infections in the future; however, further
      randomized controlled trials of these strategies are needed. Future efforts
      should concentrate on limiting the use of traditional tunneled cuffed
      hemodialysis catheters by early referral to vascular surgery for the creation of
      an arterio-venous fistula.

PMID- 16596550
TI  - Advantages of a nurse-led central venous vascular access service.
AB  - Inserting central venous catheters for patients requiring parenteral nutrition
      (PN) is expensive and time consuming, particularly if operating theatre
      facilities are used. Expanding the role of a clinical nurse specialist, with
      previous experience in critical care, enabled this procedure to be performed
      percutaneously at the bedside, cutting costs, freeing medical staff time and
      improving patient care.

PMID- 16596551
TI  - Arterio-arterial prosthetic duct (AAD) as a vascular access in hemodialysis.
AB  - Vascular access (VA) is mainly a problem confronting patients undergoing
      hemodialysis (HD). In some cases, peripheral veins are damaged or thrombosed
      because of repeated vein punctures and subsequent thrombophlebitis or
      accompanying ailments like diabetes or other kinds of vasculitis, making the use
      of conventional VA methods unsuitable. In this study, we present our experience
      using a synthetic vascular graft as an arterio-arterial duct (AAD) in the upper
      arm of patients undergoing HD, in whom other procedures had failed. In this
      procedure, we used a synthetic vascular prosthesis of
      polytetrafluoroethylene(ePTFE) (Gore-Tex) or Vasculink as an AAD, subcutaneous in
      the media aspect of the upper arm. HD was performed for this duct. Twenty
      patients were selected in whom all other VA means had failed. Patient age ranged
      from 33-83 yrs. In two patients (12%), early graft thrombosis was the cause of
      failure. In the remaining 14 patients (87%), a suitable flow was established. In
      another two patients, after several dialysis sessions the duct stopped
      functioning. We believe the reason for this malfunction was too much pressure on
      the graft to control bleeding due to the inadequate training of the HD personnel.
      The remaining 12 patients (75%) used the duct for >6 months. With this method,
      because we used only the artery for placing the conduit, complications relating
      to the vein such as limb ischemia, edema and venous hypertension did not prevail.
      On the other hand, because the conduit is an accessory duct, should it have
      become thrombosed, arterial flow to the limb would be unhindered. Therefore, we
      believe when all other conventional VA methods have failed, AAD is a suitable
      technique.

PMID- 16596552
TI  - The suitability of the femoral vein for permanent vascular access.
AB  - In our dialysis unit, we commonly position permanent catheters (the Tesio twin
      catheter) in femoral veins with 'high' exit sites, in the abdominal area. We
      prefer this method because of its intrinsic safety in patients immediately
      requiring hemodialysis (HD), because there is no need for ultrasound guidance and
      a low incidence of complications during and after positioning. In addition, we
      consider that this method is suitable for older patients without good native
      vessels for an arteriovenous fistula (AVF). Sixty-nine femoral catheters were
      positioned in 61 patients (mean age 70.8 yrs): 307 observational months/patients
      (mean duration 4.45 months) demonstrated the following results: a) no incidents
      during catheter positioning; b) four iliac-femoral thromboses (in three cases
      complete recanalization with heparin treatment); c) two catheters were removed
      due to an infection of the tunnel; d) no generalized, life-threatening sepsis.
      Therefore, we recommend this solution as a 'bridge-access' between the immediate
      need for HD and the successive best strategy for the treatment of end-stage renal
      disease (ESRD).

PMID- 16596553
TI  - Experience with the use of uncuffed double-lumen silicone hemodialysis catheters.
AB  - AIM: This study aimed to describe our experience with the use of uncuffed double
      lumen silicone hemodialysis catheters (USHDCs) that were used in 54 cases as a
      temporary vascular access (VA). SUBJECTS AND METHODS: We recorded,
      retrospectively, all the USHDCs (size 13.5 French (F), length 15, 20 and 24 cm)
      that were inserted in our dialysis unit from July 2003 to September 2004.
      Catheter and patient characteristics, as well as catheter related complications,
      were recorded. RESULTS: There were 88 catheters used in 54 cases (44 patients).
      The catheters remained in place for a total of 2537 days (range 8-127 days, mean
      46.9 +/- 31.1). For catheter placement, the internal jugular veins (group A) or
      the femoral veins (group B) were used in a non-randomized manner. In group A, in
      17 cases, 31 catheters were used for a total of 1169 days (mean 68.7 +/- 28.5),
      while in group B, in 37 cases, 57 catheters were used for a total of 1368 days
      (mean 36.9 +/- 27.1; p < 0.001). In group B, 81% of cases (30/37) were ambulatory
      from the time of insertion. Mean urea reduction ratio (URR) in well functioning
      catheters (blood flow > or = 200 ml/min) was 65.5 +/- 4.6% in group A and 56.9 +/
      6.2% in group B; p < 0.001. Catheter-related bacteremia was observed in five
      group A cases and in seven group B cases (p = ns). Three cases of minor bleeding
      at the insertion site and three cases of ipsilateral leg edema were recorded in
      group B patients. In group A, only one case of bleeding at the insertion site was
      recorded. CONCLUSION: Uncuffed double-lumen silicone hemodialysis catheters
      (USHDCs), 13.5 F in size, provided a very efficient temporary VA when placed in
      the jugular vein. Femoral placement of these catheters can also be used
      successfully in non bed-ridden patients, but delivering a lower dialysis dose.

PMID- 16596555
TI  - Preserving the left arm vein in cases of hemodialysis access generating left
      internal mammary artery steal syndrome.
AB  - In patients undergoing chronic hemodialysis (HD) through an arm arteriovenous
      fistula (AVF), coronary insufficiency can occur if the patient undergoes a
      coronary artery bypass graft (CABG) using the ipsilateral internal mammary artery
      (1-4). Therefore, the creation of a new AVF after CABG should avoid using the arm
      ipsilateral to the side where the internal thoracic artery was used. In cases
      where coronary syndrome appears when this advice is not followed, treatment
      should be offered aimed at overcoming the hemodynamic interference between the
      diminished coronary supply through the left or right internal mammary artery by
      closure of the existing fistula, with or without temporary central venous line
      insertion until the maturation of a new fistula. We suggest a different approach
      by moving only the arterial inflow site of the AVF to the controlateral
      subclavian artery, but in addition, leaving the well functioning venous outflow
      tract intact. In cases of left internal mammary steal it is achieved by creating
      a conduit running from the right subclavian artery to the left cephalic vein;
      therefore, creating a new arterial inflow source, connected to the existing
      functioning old venous outflow tract to maintain an immediately functioning new
      fistula without a coronary steal.

PMID- 16596556
TI  - Vasculorama.

PMID- 16596557
TI  - Percutaneous treatment of thrombosed arteriovenous fistulae using the Gelbfish
      Endovac aspiration thrombectomy device.
AB  - PURPOSE: To study the efficacy and safety of percutaneous treatment of thrombosed
      hemodialysis arteriovenous fistulae (AVF) using the Gelbfish-Endovac aspiration
      thrombectomy device (Gelbfish-Endovac). METHODS: From September 2003 to May 2004,
      twenty-nine percutaneous thrombectomy procedures were performed in 27 patients
      (median age of 67 years, 14 females) with thrombosed hemodialysis AVF using the
      Gelbfish-Endovac. Prior interventions, procedure time, anticoagulation, use of
      additional devices/thrombolytic agents, technical success, clinical success,
      complication rates, and patency at 30, 60 and 90 days were evaluated. RESULTS:
      Sixteen upper arm and 13 forearm AVF were declotted. Seventeen AVF had prior
      percutaneous interventions. Three AVF had not matured. Median AVF age was 9
      months. Heparin was used in 14 procedures. Sixteen arterial lesions and 25 venous
      lesions were uncovered and treated. Two AVF required the additional use of the
      Arrow-Trerotola percutaneous thrombectomy device. One AVF underwent side branch
      ligation. No thrombolytic agents were used. Median procedure time was 70 minutes.
      Initial technical success was achieved in 24 AVF and clinical success was
      achieved in 22 AVF. Eleven complications occurred. Ten AVF remained open at 30
      days, 10 at 60 days and 8 at 90 days without further interventions. With
      additional percutaneous interventions, 16 AVF remained open at 30 days, 16 at 60
      days and 15 at 90 days. CONCLUSION: The Gelbfish-Endovac aspiration thrombectomy
      device is safe and efficacious for percutaneous declotting of AVF.

PMID- 16596558
TI  - Levels of anxiety and pain during chemotherapy with peripheral versus central
      vascular access: an experimental evaluation.
AB  - PURPOSE: The purpose of this research was to evaluate pain and anxiety levels in
      patients undergoing chemotherapy via central venous catheter (CVC) and peripheral
      venous access (PVA). METHOD: The sample consisted of 56 cancer patients
      undergoing at least one chemotherapy treatment cycle. They were divided into two
      groups based on the administration method of the chemotherapeutic drug: the
      experimental group (patients with CVC) and the control group (patients with PVA).
      The instruments used were the following: for multidimensional pain evaluation the
      Italian Pain Questionnaire (QUID, devised by De Benedettis et al), and the Visual
      Analogue Scale (VAS) Chart of Pain. To evaluate the state and anxiety traits, the
      State-Trait Anxiety Inventory (STAI questionnaire, by D. Spielberg) was used, and
      we used structured interviews for the statistical survey. RESULTS: Analyzing the
      data from the STAI questionnaire, it appeared that the state-trait anxiety levels
      of the experimental group and the control group were not significantly different
      (analysis of the mean difference made using the Student's t-test). The average
      scores of the STAI questionnaire for both groups fell within the normal range.
      This indicated that the anxiety level was unaffected by the introduction of the
      device (the CVC). The data collected with the QUID questionnaire and subsequent
      statistical analysis demonstrated that the difference between the means
      (Student's t-test) of the experimental group and the control group was
      significantly lower, as regards perception of the sensorial and evaluative
      quality of pain (p=0.05) in the experimental group. From the evaluation of the
      VAS method, it appeared that the difference between the means was not significant
      in either group, although the distribution of frequency tended towards lower
      values in the experimental group with respect to the control group. This confirms
      previous QUID research where a lower pain level is recorded. CONCLUSIONS:
      Analysis of the data collected via the structured interview revealed that most of
      the CVC sample did not respond to catheter insertion as a sign of a worsening of
      their illness.

PMID- 16596559
TI  - Vacutainer filling time through subcutaneous venous access devices.
AB  - INTRODUCTION: The functionality of subcutaneous venous access devices is
      evaluated at least every time the device is accessed. This evaluation is
      subjective and actions are only undertaken when blood withdrawal and/or fluid
      injection become problematic. The function of these devices has rarely been
      evaluated objectively. The present study tried to find an objective and
      standardized way to evaluate the withdrawal speed of a newly inserted port.
      METHODS: Between October 2001 and December 2002, a prospective randomized study
      of 3 types of ports was carried out. The ability to infuse heparinized normal
      saline and to withdraw blood was evaluated by recording the filling time of a 10
      ml Vacutainer tube in 876 newly inserted central venous ports at the end of the
      surgical procedure. RESULTS: The patient groups were comparable in age, gender
      and insertion procedure characteristics (vein used, position of the port on the
      body and length of the catheter). The median time needed to fill a 10 ml
      Vacutainer tube in all ports was 17.00 sec (range 11.43-63.62 sec). The median
      filling time for BardPort was 16.36 sec (range 13.48-39.00 sec), for Celsite
      18.35 sec (range 12.03-40.00 sec) and for Port-a-cath 16.43 sec (range 11.43-63
      62 sec). A significant difference in filling time was found between the large
      bore catheters (BardPort, Port-a-cath) and the small bore catheter (Celsite) of 2
      seconds median value. CONCLUSION: Measurement of withdrawal speed provides an
      objective criterion for the quality description of blood withdrawal immediately
      after insertion. A value of more than 20 seconds for filling a 10 ml Vacutainer
      tube could therefore be suggested a useful trigger for further investigation.

PMID- 16596560
TI  - Safety of percutaneous internal jugular catheterization in cancer patients:
      prospective observational study.
AB  - PURPOSE: To determine predictors for failure and early complications of
      percutaneous internal jugular catheterization (IJC) in cancer patients. METHODS:
      Six hundred and thirty consecutive cancer patients who required central venous
      catheterization were included in a prospective observational study. The rates of
      failure (defined as the intervention of a second physician and/or failure at
      initial insertion site) and of early complications were prospectively
      ascertained. Logistic regression analysis estimated odds ratio (OR) and 95%
      confidence intervals (95% CI) for independent predictors for failure and early
      complications of percutaneous IJC. RESULTS: The failure rate was 6.7%, and the
      early complication rate was 6.7%. In multivariate analysis, left-side initial
      catheterization (p<0.01), prior catheterization at the same site (p=0.001) and
      physician inexperience (p<0.0001) were independently associated with failure.
      Placement requiring more than one needle pass (p<0.01 for two and p<0.0001 for
      three and more) and absence of fluoroscopy (p<0.0001) were independently
      associated with early complications. CONCLUSIONS: Percutaneous IJC is a valid
      option in the central venous catheterization of cancer patients due to its
      reliability and safety. Skilled physicians must manage difficult placements. If
      placement requires more than one needle pass or is made without fluoroscopy,
      patients must be carefully followed for potential complications.

PMID- 16596561
TI  - Incidence of sepsis in central venous catheter-bearing patients with hematologic
      malignancies: preliminary results.
AB  - BACKGROUND: Indwelling central venous catheters (CVCs) are essential devices in
      the management of patients with hematological disorders treated with
      chemotherapy. However, their nature predisposes patients to unwanted
      complications. METHODS: CVC-related complications were retrospectively analyzed
      in 227 hematologic patients who were consecutively admitted to our hematology
      department between May 2002 and April 2004. Patients' diagnoses comprised acute
      myeloid leukemia (36.8%), acute lymphoid leukemia (7.3%), lymphoproliferative
      disorders (28.3%), multiple myeloma (19.5%), myeloproliferative syndromes (5%)
      and others (3.1%). The CVCs used were polyurethane three lumen 7-Fr (111
      patients) for chemotherapy and 12-Fr (114 patients) for chemotherapy and
      peripheral blood stem cell apheresis, plus two tunneled catheters. RESULTS: The
      pathological events were: bacteriaemias (n=46); occlusions (n=10); exit tunnel
      infections (n=8); thrombosis (n=6); lung emboli (n=2). Among febrile patients the
      bacteriemia frequency was 20%, of which 13.6% were CVC-related (with a higher
      incidence in leukemia patients (p=0.027). Among the isolates, gram-positive
      bacteria were found in 29 cases (23 CVC-related cases), and gram-negative
      bacteria in 16 cases (8 CVC-related cases). Only one patient had Candida albicans
      sepsis. At univariate and multivariate analysis significant risk factors for
      infection (p<0.0001) were only the number of days/catheters and neutropenia
      duration. CONCLUSIONS: In our hematologic patients, the CVC complications were
      mainly septic, with only 10.1% of CVC-related bacteriemias, despite prolonged
      catheterization duration. Acute leukemia patients were at major risk for sepsis,
      probably due to a more severe neutropenia and prolonged catheterization duration.

PMID- 16596562
TI  - Complications and management of long-term central venous access catheters and
      ports.
AB  - PURPOSE: Although prolonged venous access devices (PVADs) are used in case
      prolonged intravenous therapy is required, implantation and use of these devices
      is associated with complications. The purpose of this study was to evaluate
      perioperative and long-term complications associated with PVADs and the
      management of these complications. METHODS: A retrospective review was undertaken
      of 225 PVADs implanted in 217 patients from February 1993 to June 2004. This
      included 144 single-lumen port infusion systems, 49 single-lumen Hickman
      catheters and 32 double-lumen Groshong catheters. The PVADs were inserted using
      either the percutaneous Seldinger method (n=183) or cutdown access to the
      subclavian vein (n=42). Indications for placement were as follows: chemotherapy
      in 66.2% of patients, drug-infusion treatment in 31.6% of patients and total
      parenteral nutrition in 2.2% of patients. RESULTS: Perioperative complications
      occurred in 13 patients (5.7%): catheter malposition in seven patients (3.1%),
      pneumothorax in three patients (1.3%), hemorrhage in two patients (0.9%) and
      catheter embolization in one patient (0.4%). Long-term complications appeared in
      15 patients (6.6%): infection in five patients (2.2%), thrombosis in three
      patients (1.3%), extravasation in three patients (1.3%), and catheter fracture in
      four patients (1.8%). The fractured fragments were removed by the Amplatz snare
      device. In 10 patients (4.4%) only were PVADs removed prior to completion of the
      intended therapy. Indications for removal were catheter infection in five
      patients (2.2%) and catheter fracture in five patients (2.2%). CONCLUSIONS: PVAD
      implantation is associated with some risk of serious perioperative and long-term
      complications. Care of the catheter and the patient should be maintained with the
      proper and immediate evaluation of the perioperative and long-term complications.

PMID- 16596563
TI  - Bicyclic glutamic acid derivatives.
AB  - For the second-generation asymmetric synthesis of the trans-tris(homoglutamic)
      acids via Strecker reaction of chiral ketimines, the cyanide addition as the key
      stereodifferentiating step produces mixtures of diastereomeric alpha-amino
      nitrile esters the composition of which is independent of the reaction
      temperature and the type of the solvent, respectively. The subsequent hydrolysis
      is exclusively achieved with concentrated H(2)SO(4) yielding diastereomeric
      mixtures of three secondary alpha-amino alpha-carbamoyl-gamma-esters and two
      diastereomeric cis-fused angular alpha-carbamoyl gamma-lactams as bicyclic
      glutamic acid derivatives, gained from in situ stereomer differentiating
      cyclisation of the secondary cis-alpha-amino alpha-carbamoyl-gamma-esters.
      Separation was achieved by CC. The pure secondary trans-alpha-amino alpha
      carbamoyl-gamma-esters cyclise on heating and treatment with concentrated
      H(2)SO(4), respectively, to diastereomeric cis-fused angular secondary alpha
      amino imides. Their hydrogenolysis led to the enantiomeric cis-fused angular
      primary alpha-amino imides. The configuration of all compounds was completely
      established by NMR methods, CD-spectra, and by X-ray analyses of the
      (alphaR,1R,5R)-1-carbamoyl-2-(1-phenylethyl)-2-azabicyclo[3.3.0]octan-3-one and
      of the trans-alphaS,1S,2R-2-ethoxycarbonylmethyl-1-(1
      phenylethylamino)cyclopentanecarboxamide.

PMID- 16596564
TI  - Magnetic resonance imaging measures of brain atrophy in multiple sclerosis.
AB  - Magnetic resonance imaging (MRI) has been widely used to diagnose and monitor
      multiple sclerosis (MS). Although MRI-visible lesions are a key feature of MS,
      they are thought to correlate poorly with clinical progression. Neurodegeneration
      is increasingly being recognized as an important factor in the pathogenesis of
      MS, and MRI measures of brain atrophy have been suggested as surrogate markers of
      neuroaxonal loss and disease progression. This pathology may be more relevant to
      the progression of disability than focal inflammation. A number of MRI-based
      methods have been developed for the measurement of global and regional brain
      atrophy. Natural-history studies of MS and clinically isolated syndromes
      suggestive of MS have observed atrophy in these subjects above that seen in
      controls, over periods ranging from three months to years. Brain atrophy has also
      been incorporated as an outcome measure in therapeutic trials of disease
      modifying treatments. This paper considers neuroaxonal loss and the pathological
      basis of brain atrophy, methods developed to quantify brain atrophy, the findings
      of natural-history and therapeutic studies, the relationship of brain atrophy to
      disability and cognition, and the future research directions and clinical
      applications of brain atrophy measurements.

PMID- 16596566
TI  - Pierre Potier (1934-2006).

PMID- 16596567
TI  - Tetracyanoethylene (TCNE): the characteristic geometries and vibrational
      absorptions of its numerous structures.
AB  - Tetracyanoethylene (TCNE) undergoes numerous reactions and is reported to exist
      in many structural motifs. Identification of these forms and motifs can be
      challenging. Nonetheless, the number of nu(CN) absorptions and their frequencies
      provide insight with respect to the specific forms and charge on the TCNE
      fragment. Particularly informative is the average of the fundamental nu(CN)
      bands, as well as the length of the central C-C bond. This Review discusses the
      assignment of structure and formal charge for TCNE-containing compounds. Scrutiny
      of previous assignments reveals some discrepancies which are discussed, and
      provides a basis for further study of TCNE structure-function relationships.
      Several multimetal complexes with bridging [TCNE](z) units exhibit mixed valency
      and extensive delocalization. The scarcity of suitable model compounds,
      especially those with M(d(pi-pi*)) backbonding to the CN groups, have thwarted
      the detailed description of these valence ambiguous compounds; thus, new well
      characterized polynuclear compounds are needed.

PMID- 16596569
TI  - Crystal structure of Homo sapiens thialysine Nepsilon-acetyltransferase (HsSSAT2)
      in complex with acetyl coenzyme A.

PMID- 16596570
TI  - A simple measure of native-state topology and chain connectivity predicts the
      folding rates of two-state proteins with and without crosslinks.
AB  - The folding rates of two-state proteins have been found to correlate with simple
      measures of native-state topology. The most prominent among these measures is the
      relative contact order (CO), which is the average CO, or localness, of all
      contacts in the native protein structure, divided by the chain length. Here, we
      test whether such measures can be generalized to capture the effect of chain
      crosslinks on the folding rate. Crosslinks change the chain connectivity and
      therefore also the localness of some of the native contacts. These changes in
      localness can be taken into account by the graph-theoretical concept of effective
      contact order (ECO). The relative ECO, however, the natural extension of the
      relative CO for proteins with crosslinks, overestimates the changes in the
      folding rates caused by crosslinks. We suggest here a novel measure of native
      state topology, the relative logCO, and its natural extension, the relative
      logECO. The relative logCO is the average value for the logarithm of the CO of
      all contacts, divided by the logarithm of the chain length. The relative log(E)CO
      reproduces the folding rates of a set of 26 two-state proteins without crosslinks
      with essentially the same high correlation coefficient as the relative CO. In
      addition, it also captures the folding rates of eight two-state proteins with
      crosslinks.

PMID- 16596571
TI  - Some design issues of strata-matched non-randomized studies with survival
      outcomes.
AB  - Non-randomized studies for the evaluation of a medical intervention are useful
      for quantitative hypothesis generation before the initiation of a randomized
      trial and also when randomized clinical trials are difficult to conduct. A strata
      matched non-randomized design is often utilized where subjects treated by a test
      intervention are matched to a fixed number of subjects treated by a standard
      intervention within covariate based strata. In this paper, we consider the issue
      of sample size calculation for this design. Based on the asymptotic formula for
      the power of a stratified log-rank test, we derive a formula to calculate the
      minimum number of subjects in the test intervention group that is required to
      detect a given relative risk between the test and standard interventions. When
      this minimum number of subjects in the test intervention group is available, an
      equation is also derived to find the multiple that determines the number of
      subjects in the standard intervention group within each stratum. The methodology
      developed is applied to two illustrative examples in gastric cancer and sarcoma.

PMID- 16596572
TI  - Much ado about nothing: a comparison of the performance of meta-analytical
      methods with rare events.
AB  - For rare outcomes, meta-analysis of randomized trials may be the only way to
      obtain reliable evidence of the effects of healthcare interventions. However,
      many methods of meta-analysis are based on large sample approximations, and may
      be unsuitable when events are rare. Through simulation, we evaluated the
      performance of 12 methods for pooling rare events, considering estimability,
      bias, coverage and statistical power. Simulations were based on data sets from
      three case studies with between five and 19 trials, using baseline event rates
      between 0.1 and 10 per cent and risk ratios of 1, 0.75, 0.5 and 0.2. We found
      that most of the commonly used meta-analytical methods were biased when data were
      sparse. The bias was greatest in inverse variance and DerSimonian and Laird odds
      ratio and risk difference methods, and the Mantel-Haenszel (MH) odds ratio method
      using a 0.5 zero-cell correction. Risk difference meta-analytical methods tended
      to show conservative confidence interval coverage and low statistical power at
      low event rates. At event rates below 1 per cent the Peto one-step odds ratio
      method was the least biased and most powerful method, and provided the best
      confidence interval coverage, provided there was no substantial imbalance between
      treatment and control group sizes within trials, and treatment effects were not
      exceptionally large. In other circumstances the MH OR without zero-cell
      corrections, logistic regression and the exact method performed similarly to each
      other, and were less biased than the Peto method.

PMID- 16596573
TI  - A penalized likelihood approach to magnetic resonance image reconstruction.
AB  - Currently, images acquired via magnetic resonance imaging (MRI) and functional
      magnetic resonance imaging (fMRI) technology are reconstructed using the discrete
      inverse Fourier transform. While computationally convenient, this approach is not
      able to filter out noise. This is a serious limitation because the amount of
      noise in MRI and fMRI can be substantial. In this paper, we propose an
      alternative approach to reconstruction, based on penalized likelihood
      methodology. In particular, we focus on non-linear shrinkage estimators and show
      that this approach achieves a great reduction in integrated mean squared error
      (IMSE) of the estimated image with respect to the currently used estimator. This
      approach is extremely fast and easy to implement computationally. In addition, it
      can be combined with various alternative approaches to MR image reconstruction
      and can be easily adapted to other, non-MRI contexts, in which the observed data
      and the quantities of interest are related via a linear transform.

PMID- 16596574
TI  - A flexible model for multivariate interval-censored survival times with complex
      correlation structure.
AB  - We focus on the analysis of multivariate survival times with highly structured
      interdependency and subject to interval censoring. Such data are common in
      developmental genetics and genetic epidemiology. We propose a flexible mixed
      probit model that deals naturally with complex but uninformative censoring. The
      recorded ages of onset are treated as possibly censored ordinal outcomes with the
      interval censoring mechanism seen as arising from a coarsened measurement of a
      continuous variable observed as falling between subject-specific thresholds. This
      bypasses the requirement for the failure times to be observed as falling into non
      overlapping intervals. The assumption of a normal age-of-onset distribution of
      the standard probit model is relaxed by embedding within it a multivariate Box
      Cox transformation whose parameters are jointly estimated with the other
      parameters of the model. Complex decompositions of the underlying multivariate
      normal covariance matrix of the transformed ages of onset become possible. The
      new methodology is here applied to a multivariate study of the ages of first use
      of tobacco and first consumption of alcohol without parental permission in twins.
      The proposed model allows estimation of the genetic and environmental effects
      that are shared by both of these risk behaviours as well as those that are
      specific.

PMID- 16596575
TI  - A method for therapeutic dose selection in a phase II clinical trial using
      contrast statistics.
AB  - This paper proposes a statistical method for determining the therapeutic dose of
      a test drug in a confirmatory clinical trial based on a phase II clinical trial
      using 3 or 4 doses of the drug. This method assumes the primary variable has a
      normal distribution with a common variance, that a test-drug effect is seen when
      the population means show a response pattern indicating a monotonic increase with
      dose, and that there is a prior distribution for the population means. Under the
      proposed method, multiple contrast statistics are determined, such as contrast
      statistics for linear increase and plateau, and a response pattern is selected
      based on the maximum contrast statistic. The posterior probability that the
      selected response pattern is the true one is evaluated, and if this exceeds the
      cut-off value a therapeutic dose is selected based on the estimated response
      pattern. To select the appropriate cut-off value, a simulation study was
      conducted using a loss function for which the loss due to overestimation is
      greater than the loss due to underestimation. It was found that, as a rule, the
      appropriate cut-off value to reduce the expected loss for various response
      patterns is 0.75 for a 3-group trial and 0.70 for a 4-group trial. Using these
      cut-off values, the proposed method was applied to a previous clinical trial of a
      leukotriene receptor antagonist in patients with bronchial asthma. The method
      enabled the selection of what are considered appropriate response patterns and a
      therapeutic dose. Thus, the proposed method appears reasonable.

PMID- 16596576
TI  - A dose-response test via closed-form solutions for constrained MLEs in
      survival/sacrifice experiments.
AB  - In most survival-sacrifice experiments in animal carcinogenicity studies, the
      onset of the tumour of interest is not clinically observable. Due to the
      complexity of constraints for a biological justification, recently developed
      methods for estimating the tumour onset function and tumour-specific survival
      function employ computer-intensive numerical solutions. In this paper, closed
      form solutions for nonparametric maximum likelihood estimators are derived under
      explicit and implicit inequality constraints obtained from the monotonicity of
      the survival functions. Our methods do not require cause-of-death information.
      The proposed methods can be used to estimate the tumour onset function and the
      survival function of the tumour of interest. We use the proposed estimators for
      the development of our new dose-response trend test. A modification of the Poly-k
      test is made by replacing the time-at-risk weight to a function of the tumour
      onset survival function. The weighted least square regression method is applied
      to the estimated survival functions in order to construct a dose-response trend
      test. A simulation study is conducted to evaluate the performance of the proposed
      test and compare it with existing trend tests. A real example is used to
      illustrate the methods.

PMID- 16596577
TI  - Model selection for incomplete and design-based samples.
AB  - The Akaike information criterion, AIC, is one of the most frequently used methods
      to select one or a few good, optimal regression models from a set of candidate
      models. In case the sample is incomplete, the naive use of this criterion on the
      so-called complete cases can lead to the selection of poor or inappropriate
      models. A similar problem occurs when a sample based on a design with unequal
      selection probabilities, is treated as a simple random sample. In this paper, we
      consider a modification of AIC, based on reweighing the sample in analogy with
      the weighted Horvitz-Thompson estimates. It is shown that this weighted AIC
      criterion provides better model choices for both incomplete and design-based
      samples. The use of the weighted AIC-criterion is illustrated on data from the
      Belgian Health Interview Survey, which motivated this research. Simulations show
      its performance in a variety of settings.

PMID- 16596578
TI  - A comparison of methods for the analysis of recurrent health outcome data with
      environmental covariates.
AB  - Recurrent events such as repeated hospital admissions for the same health outcome
      occur frequently in environmental health studies. Dewanji and Moolgavkar proposed
      a flexible parametric model and a conditional likelihood analysis for recurrent
      events based on a Poisson process formulation. In this paper, we examine the
      statistical properties of the Dewanji-Moolgavkar (DM) estimator of the risk of an
      adverse health outcome associated with environmental exposures based on recurrent
      event data using computer simulation. We also compare the DM approach with both
      case-crossover analysis for multiple observations and time series analysis when
      there are no subject-specific covariates. When using a correctly specified model,
      the DM method produced better estimates with respect to relative mean square
      error when each subject had constant or curved baseline intensity functions than
      it did when baseline intensities were increasing or decreasing in a linear
      fashion. For under-specified models, the DM method outperformed case-crossover
      analysis for decreasing straight line intensity functions, was outperformed by
      case-crossover analysis for increasing straight line intensity functions, and was
      roughly equivalent to case-crossover analysis for constant and curved intensity
      functions. Case-crossover analysis produced superior risk estimates more
      frequently than the other two methods in the cases considered here, especially
      for linear representations of the baseline intensities.

PMID- 16596579
TI  - Gaussianization-based quasi-imputation and expansion strategies for incomplete
      correlated binary responses.
AB  - New quasi-imputation and expansion strategies for correlated binary responses are
      proposed by borrowing ideas from random number generation. The core idea is to
      convert correlated binary outcomes to multivariate normal outcomes in a sensible
      way so that re-conversion to the binary scale, after performing multiple
      imputation, yields the original specified marginal expectations and correlations.
      This conversion process ensures that the correlations are transformed reasonably
      which in turn allows us to take advantage of well-developed imputation techniques
      for Gaussian outcomes. We use the phrase 'quasi' because the original
      observations are not guaranteed to be preserved. We argue that if the inferential
      goals are well-defined, it is not necessary to strictly adhere to the established
      definition of multiple imputation. Our expansion scheme employs a similar
      strategy where imputation is used as an intermediate step. It leads to
      proportionally inflated observed patterns, forcing the data set to a complete
      rectangular format. The plausibility of the proposed methodology is examined by
      applying it to a wide range of simulated data sets that reflect alternative
      assumptions on complete data populations and missing-data mechanisms. We also
      present an application using a data set from obesity research. We conclude that
      the proposed method is a promising tool for handling incomplete longitudinal or
      clustered binary outcomes under ignorable non-response mechanisms.

PMID- 16596580
TI  - Interval estimation for rank correlation coefficients based on the probit
      transformation with extension to measurement error correction of correlated
      ranked data.
AB  - The Spearman (rho(s)) and Kendall (tau) rank correlation coefficient are
      routinely used as measures of association between non-normally distributed random
      variables. However, confidence limits for rho(s) are only available under the
      assumption of bivariate normality and for tau under the assumption of asymptotic
      normality of tau. In this paper, we introduce another approach for obtaining
      confidence limits for rho(s) or tau based on the arcsin transformation of sample
      probit score correlations. This approach is shown to be applicable for an
      arbitrary bivariate distribution. The arcsin-based estimators for rho(s) and tau
      (denoted by rho(s,a), tau(a)) are shown to have asymptotic relative efficiency
      (ARE) of 9/pi2 compared with the usual estimators rho(s) and tau when rho(s) and
      tau are, respectively, 0. In some nutritional applications, the Spearman rank
      correlation between nutrient intake as assessed by a reference instrument versus
      nutrient intake as assessed by a surrogate instrument is used as a measure of
      validity of the surrogate instrument. However, if only a single replicate (or a
      few replicates) are available for the reference instrument, then the estimated
      Spearman rank correlation will be downwardly biased due to measurement error. In
      this paper, we use the probit transformation as a tool for specifying an ANOVA
      type model for replicate ranked data resulting in a point and interval estimate
      of a measurement error corrected rank correlation. This extends previous work by
      Rosner and Willett for obtaining point and interval estimates of measurement
      error corrected Pearson correlations.

PMID- 16596581
TI  - Nonparametric bounds on the effect of deductibles in health care insurance on
      doctor visits - Swiss evidence.
AB  - We evaluate the effect of the size of deductibles in the basic health insurance
      in Switzerland on the probability of a doctor visit. We employ nonparametric
      bounding techniques to minimise statistical assumptions. In order to tighten the
      bounds we consider two further assumptions: mean independence of an instrument
      and monotone treatment response. Under these two assumption we are able to bound
      the causal effect of high deductibles compared to low deductibles below zero. We
      conclude that the difference in health care utilisation is partly due to a
      reduction of moral hazard effects.

PMID- 16596582
TI  - Pronounced individual variation in the response to the stimulatory action of
      exercise on immature hippocampal neurons.
AB  - In the adult hippocampus, neurogenesis is influenced both by external stimuli,
      such as physical exercise, and by intrinsic conditions like age and disease.
      However, the way in which many of these external and internal cues interact in
      this process remains poorly understood. We have used a new, more precise,
      stereological cell counting method that involves confocal microscopy to analyze
      the effects of exercise on adult neurogenesis in the mouse. We found that
      treadmill exercise increases the number of differentiating neurons
      (doublecortin/calretinin cells) in the granule cell layer of the mouse
      hippocampus in a manner that is directly related to the size of the mature
      granule cell population. More immature neurons were found after exercise in
      animals that had a larger dentate gyrus (DG), while no changes were observed in
      those with a smaller DG. This differential response to physical exercise suggests
      that the pre-existing neuronal population regulates the neurogenic response in
      the DG to external stimuli. These data raise the possibility of anticipating an
      individuals' response to therapeutic interventions (like exercise) aimed at
      augmenting dentate neurogenesis and alleviating or preventing cognitive decline.

PMID- 16596583
TI  - The structure of the bond between bone and porous silicon-substituted
      hydroxyapatite bioceramic implants.
AB  - The significance of micrometer-sized strut porosity in promoting bone ingrowth
      into porous hydroxyapatite (HA) scaffolds has only recently been noted. In this
      study, silicon-substituted HA (0.8 wt % Si-HA) with approximately 8.5% of the
      total porosity present as microporosity within the struts of the implant was
      prepared for high-resolution transmission electron microscopy (HR-TEM) via both
      ultramicrotomy and focused ion beam milling. Between the struts of the porous Si
      HA, pores with varying shapes and sizes (1-10 microm in diameter) were
      characterized. Within the struts, the Si-HA contained features such as grain
      boundaries and triple-junction grain boundaries. Bone ingrowth and dissolution
      from a Si-HA implant were studied using HR-TEM after 6 weeks in vivo. Minor local
      dissolution occurred within several pores within the struts. Organized,
      mineralized collagen fibrils had grown into the strut porosity at the interface
      between the porous Si-HA implant and the surface of the surrounding bone. In
      comparison, deeper within the implant, disorganized and poorly mineralized fibers
      were observed within the strut porosity. These findings provide valuable insight
      into the development of bone around porous Si-HA implants.

PMID- 16596584
TI  - Durability of a cardiac valve leaflet made of calf pericardium: fatigue and
      energy consumption.
AB  - We studied the mechanical behavior of membranes of calf pericardium, similar to
      those employed in prosthetic valve leaflets, when subjected to tensile fatigue.
      The objective was to assess its durability, as a fundamental property of cardiac
      bioprosthesis, and analyze the energy consumption. For this purpose, the authors
      built a hydraulic simulator to subject a spherical valve leaflet made of calf
      pericardium to cyclic stress mimicking cardiac function. A total of 522 assays
      were performed in 40 samples, subjected to cyclic pressures greater than 6 atm,
      and 482 subjected to pressures ranging between 2 and 6 atm. The mathematical
      expression that establishes the relationship between the pressure exerted and the
      frequency was obtained. If we assume that the function is continuous, this
      equation provides the range of fatigue tolerated for a given number of cycles.
      Using the optimal values (the five highest values per series), the expression was
      found to be y = 9.95x(-0 1214) (R(2) = 0.955), where x represents the frequency
      in cycles per second and y the pressure in atmospheres. In addition, we
      established the mathematical relationship between the energy consumed and the
      frequency, which was a function of the pressure exerted, regardless of the region
      or zone from which the samples had been obtained. The methods of manual and
      morphology-based selection employed produced widely dispersed results. When a
      mechanical criterion was included, the similarity in the energy consumed during
      fatigue testing markedly improved the correlation, with a coefficient of
      determination between paired samples of R(2) = 0.7477. A mechanical criterion,
      such as energy consumption, can help to improve sample selection and produce more
      consistent results. Finally, we obtained the mathematical expression that relates
      the energy consumed to the pressure exerted and the number of cycles per second
      to which the valve leaflet was subjected. This procedure enables us to establish
      the limit to the energy that a biomaterial can consume over a period of time
      during which it is subjected to a working pressure and, thus, calculate more
      precisely its durability.

PMID- 16596585
TI  - Cartilage tissue engineering using human auricular chondrocytes embedded in
      different hydrogel materials.
AB  - To seek a suitable scaffold for cartilage tissue engineering, we compared various
      hydrogel materials originating from animals, plants, or synthetic peptides. Human
      auricular chondrocytes were embedded in atelopeptide collagen, alginate, or
      PuraMatrix, all of which are or will soon be clinically available. The
      chondrocytes in the atelopeptide collagen proliferated well, while the others
      showed no proliferation. A high-cell density culture within each hydrogel
      enhanced the expression of collagen type II mRNA, when compared with that without
      hydrogel. By stimulation with insulin and BMP-2, collagen type II and
      glycosaminoglycan were significantly accumulated within all hydrogels.
      Chondrocytes in the atelopeptide collagen showed high expression of beta1
      integrin, seemingly promoting cell-matrix signaling. The N-cadherin expression
      was inhibited in the alginate, implying that decrease in cell-to-cell contacts
      may maintain chondrocyte activity. The matrix synthesis in PuraMatrix was less
      than that in others, while its Young's modulus was the lowest, suggesting a
      weakness in gelling ability and storage of cells and matrices. Considering
      biological effects and clinical availability, atelopeptide collagen may be
      accessible for clinical use. However, because synthetic peptides can control the
      risk of disease transmission and immunoreactivities, some improvement in gelling
      ability would provide a more useful hydrogel for ideal cartilage regeneration.

PMID- 16596586
TI  - Nanoparticles of poly(D,L-lactide)/methoxy poly(ethylene glycol)-poly(D,L
      lactide) blends for controlled release of paclitaxel.
AB  - Paclitaxel is one of the best antineoplastic drugs found in nature in the past
      decades, which has excellent therapeutic effects against a wide spectrum of
      cancers. Because of its high hydrophobicity, Cremophor EL has to be used as
      adjuvant in its clinical dosage form (Taxol), which has been found to cause
      serious side effects. Nanoparticles of biodegradable polymers may provide an
      ideal solution. In this research, paclitaxel-loaded nanoparticles of poly(D,L
      lactide)/methoxy poly(ethylene glycol)-polylactide (PLA/MPEG-PLA) blends of
      various blend ratio 100/0, 75/25, 50/50, 25/75, and 0/100 were formulated by the
      nanoprecipitation method for controlled release of paclitaxel. It was found that
      increasing the proportion of MPEG-PLA component in the blend from 0 to 100%
      resulted in a progressive decrease of the particle size from 230.6+/-11.1 nm to
      74.8+/-14.0 nm. The zeta potential of the drug-loaded nanoparticles was increased
      accordingly from -19.60+/-1.13 mV to a nearly neutral, that is, -0.33+/-0.28 mV,
      which indicates the gradual enrichment of PEG segments on the particle surface.
      The findings were further confirmed by X-Ray Photoelectron Spectroscopy (XPS)
      analysis. Differential scanning calorimetry (DSC) analysis showed that the glass
      transition temperature of PLA was significantly decreased from 58.7 to 52.1
      degrees C with an increase of MPEG-PLA proportion from 0 to 75%, suggesting the
      miscibility of PLA and MPEG-PLA. The pure PLA nanoparticles (100/0) exhibited the
      slowest drug-release rate with 37.3% encapsulated drug released from the
      nanoparticles for 14 days while the MPEG-PLA nanoparticles (0/100) achieved the
      fastest drug release with 95.9% drug release in the same period.

PMID- 16596587
TI  - A novel tool for high-resolution transmission electron microscopy of intact
      interfaces between bone and metallic implants.
AB  - A key feature in the understanding of the mechanisms of integration versus
      rejection of implanted materials is a deepened understanding of the elemental and
      molecular compositions of the interface zone between the surface of the synthetic
      man-made material and the biological components of tissue. Intact interfaces
      between metallic implants and tissues have not been able to image and analyse on
      the ultrastructural level with the common transmission electron microscopy (TEM)
      sample preparation techniques. By using focused ion beam microscopy for site
      specific preparation of TEM samples, intact interfaces between metal implants and
      calcified tissue were imaged for the first time. The interface's elemental and
      crystallographic compositions were determined using energy dispersive X-ray
      mapping and electron diffraction. The developed technique fulfills a long-sought
      for demand to correlate the surface properties of implanted metal prostheses with
      the fine structure and composition of preserved interfaces with tissues.

PMID- 16596588
TI  - Polymethylmethacrylate particles inhibit osteoblastic differentiation of bone
      marrow osteoprogenitor cells.
AB  - Aseptic implant loosening of total joint replacements often results from particle
      mediated bone loss, which may be a combined effect of osteolysis and suppressed
      bone formation. Bone regeneration in the prosthetic bed depends on the activity
      of osteoblasts and their differentiation from osteoprogenitors in the bone
      marrow. This study investigated the effects of polymethylmethacrylate (PMMA)
      particles on the ability of bone marrow osteoprogenitors to differentiate into
      osteoblasts in vitro. Murine bone marrow cells challenged with PMMA particles on
      the first day of differentiation in osteogenic medium showed a dose-dependent
      decrease in osteoprogenitor proliferation, alkaline phosphatase expression, and
      mineralization. Undifferentiated bone marrow cells pretreated with PMMA particles
      in nonosteogenic medium for 5 days also showed a dose-dependent loss in
      osteogenic potential, which was sustained throughout subsequent growth in
      particle-free, osteogenic medium. Bone marrow cells challenged with PMMA
      particles after the fifth day of differentiation in osteogenic medium showed
      significant reductions in cellular proliferation, but not alkaline phosphatase
      expression and mineralization, indicating that bone marrow cells were most
      sensitive to particle treatment during the first 5 days of differentiation. This
      study demonstrated that PMMA particles inhibit osteoblastic differentiation of
      bone marrow osteoprogenitor cells, which may contribute to periprosthetic bone
      loss and implant failure.

PMID- 16596589
TI  - Primate remains from African crowned eagle (Stephanoaetus coronatus) nests in
      Ivory Coast's Tai Forest: implications for primate predation and early hominid
      taphonomy in South Africa.
AB  - Understanding the initial processes of deposition can help with interpretations
      of fossil assemblages. Here we discuss the taphonomy of primate remains collected
      under 16 nests of African crowned eagles (Stephanoaetus coronatus) in the Tai
      Forest, Ivory Coast. From 1,200 bones collected, including 669 primate bones, we
      calculated minimum number of individuals (MNI), survivability profiles, and
      damage profiles using methods identical to those employed by Sanders et al. (2003
      J. Hum. Evol. 44:87-105) in their analysis of bones from eagle nests in Uganda.
      Crowned eagles leave a consistent taphonomic signature on their prey remains;
      hence, results from our analysis of the Tai assemblage are similar to those from
      the Ugandan sample. Hindlimb and cranial bones are relatively abundant in the
      sample, while ribs, vertebrae, carpals, and tarsals do not survive well. Primate
      crania typically display puncture marks around the eye, long bones remain largely
      intact, and scapulae exhibit raked breakage. These data have implications for
      understanding the dynamic between extant primates and one of their principle
      predators, as well as the taphonomy of hominid-bearing caves in South Africa. We
      concur with Berger and Clarke (1995 J. Hum. Evol. 29:275-299) that a large raptor
      could have been responsible for the death of the Taung child, Australopithecus
      africanus.

PMID- 16596590
TI  - Mitochondrial genomics identifies major haplogroups in Aboriginal Australians.
AB  - We classified diversity in eight new complete mitochondrial genome sequences and
      41 partial sequences from living Aboriginal Australians into five haplogroups.
      Haplogroup AuB belongs to global lineage M, and AuA, AuC, AuD, and AuE to N.
      Within N, we recognize subdivisions, assigning AuA to haplogroup S, AuD to
      haplogroup O, AuC to P4, and AuE to P8. On available evidence, (S)AuA and (M)AuB
      are widespread in Australia. (P4)AuC is found in the Riverine region of western
      New South Wales, and was identified by others in northern Australia. (O)AuD and
      (P8)AuE were clearly identified only from central Australia. Our eight Australian
      full mt genome sequences, combined with 20 others (Ingman and Gyllensten 2003
      Genome Res. 13:1600-1606) and compared with full mt genome sequences from regions
      to the north that include Papua New Guinea, Malaya, and Andaman and Nicobar
      Islands, show that ancestral connections between regions are deep and limited to
      clustering at the level of the N and M macrohaplogroups. The Australian-specific
      distribution of the five haplogroups identified indicates genetic isolation over
      a long period. Ancestral connections within Australia are deeper than those
      reflected by known linguistic or culturally based affinities. Applying a
      coalescence analysis to a gene tree for the coding regions of the eight genomic
      sequences, we made estimates of time depth that support a continuity of presence
      for the descendants of a founding population already established by 40,000 years
      ago.

PMID- 16596591
TI  - Population origins in Mongolia: genetic structure analysis of ancient and modern
      DNA.
AB  - In the present study, nuclear (autosomal and Y-chromosome short tandem repeats)
      and mitochondrial (hypervariable region I) ancient DNA data previously obtained
      from a 2,300-year-old Xiongnu population of the Egyin Gol Valley (south of Lake
      Baikal in northern Mongolia) (Keyser-Tracqui et al. 2003 Am. J. Hum. Genet.
      73:247-260) were compared with data from two contemporary Mongolian populations:
      one from the same location (Egyin Gol Valley plus a perimeter of less than 100 km
      around the valley), and one from the whole of Mongolia. The principal objective
      of this comparative analysis was to assess the likelihood that genetic continuity
      exists between ancient and present-day Mongolian populations. Since the ancient
      Xiongnu sample might have been composed of some of the ancestors of the present
      day Yakuts, data from a present-day Yakut population, as well as published data
      from Turkish populations, were also included in the comparative analysis. The
      main result of our study was the genetic similarity observed among Mongolian
      samples from different periods and geographic areas. This result supports the
      hypothesis that the succession over time of different Turkic and Mongolian tribes
      in the current territory of Mongolia resulted in cultural rather than genetic
      exchanges. Furthermore, it appears that the Yakuts probably did not find their
      origin among the Xiongnu tribes, as we previously hypothesized.

PMID- 16596593
TI  - Sifaka positional behavior: ontogenetic and quantitative genetic approaches.
AB  - In many primate species, hands and feet are large relative to neonatal body
      weight, and they subsequently exhibit negative allometric growth during ontogeny.
      Here, data are presented showing that this pattern holds for a wild population of
      lemur, Verreaux's sifaka (Propithecus verreauxi verreauxi). Using morphometric
      data collected on this population, it is shown that younger animals possess
      relatively large hands and feet. This ontogenetic pattern suggests a simple
      behavioral test: do juvenile animals with their larger, almost adult-sized hands
      and feet locomote on similarly sized substrates as adult animals? Using locomotor
      bout sampling, this question was tested by collecting positional behavior data on
      this population. Results from this test find no differences in locomotor
      behaviors or substrate use between yearlings and adult animals. To place these
      results in a broader evolutionary context, heritabilities and selection gradients
      of hands, feet, and other limb elements for animals in this population were
      estimated. Among limb elements, heritabilities range from 0.16-0.44, with the
      foot having the lowest value. Positive directional selection acts most strongly
      on the foot (directional selection gradient = 0.119). The low heritability and
      positive selection coefficient indicate that selection has acted, and continues
      to act, on foot size in young animals. These results are interpreted within a
      functional context with respect to the development of locomotor coordination:
      larger feet enable young animals to use "adult-sized" substrates when they move
      through their habitat. It is suggested that the widespread pattern of negative
      allometry of the extremities in sifaka and other primates is maintained by
      selection, and does not simply reflect a primitive developmental pathway that has
      no adaptive basis.

PMID- 16596594
TI  - Dimensions of health and social structure in the early intermediate period
      cemetery at Villa El Salvador, Peru.
AB  - This paper examines relationships between the social structure of a community and
      the health of its members, based on analysis of human skeletal remains (N = 64)
      from Villa El Salvador XII (100 BC-AD 100), a prehistoric cemetery located in the
      lower Lurin Valley, Peru. The ambiguity of social status as conventionally
      inferred from archaeological context is among the principal complicating factors
      in such an inquiry. We use multidimensional scaling of skeletal markers to
      identify the presence of patterned health-based heterogeneity in our sample,
      without making a priori assumptions about underlying social structure at Villa El
      Salvador. This procedure situates every skeleton relative to all others in the
      sample on the basis of multiple health markers, eliciting health groups. Once
      recognized, the relevance of those groups to social structure can be evaluated by
      comparison with a broad range of presumptive archaeological status indicators. We
      test the hypothesis that the distribution of stress indicators in human skeletons
      covaries with archaeological indicators of social differentiation. Based on
      multivariate analysis of skeletal indicators, we conclude that the cemetery at
      Villa El Salvador was utilized by two social groups with different geographic
      affinities: one of local coastal origin, and the other probably from the upper
      Lurin Valley or adjacent higher altitudes. These groups differ in skeletal
      characteristics related to childhood health, probably reflecting systematic
      contrasts in the growth environments of the studied individuals. This same
      division is independently supported by the distribution of cranial deformation, a
      possible marker of ethnicity. We also document some inequality in the
      distribution of labor among male individuals, as reflected by the relative
      advancement of degenerative joint disease, and congruent with differences in the
      number and quality of associated funerary offerings.

PMID- 16596596
TI  - Changes in body fat distribution in relation to parity in American women: a
      covert form of maternal depletion.
AB  - Using data from the Third National Health and Nutrition Examination Survey
      (NHANES III), conducted from 1988-1994, we investigated the effect of
      reproduction on the distribution of body fat in well-nourished American women.
      While women tend to gain weight and fat with succeeding pregnancies, if age and
      body mass index are controlled, increasing parity is associated with a decrease
      in hip and thigh circumferences, suprailiac and thigh skinfolds, and body fat
      estimated from skinfolds, while waist circumference increases, resulting in a
      relative decrease in lower-body fat. The mobilization of fat stores in the lower
      body during late pregnancy and lactation may help to meet the special needs of
      the developing brain for essential fatty acids and energy during the time of peak
      growth. When fat is regained after the postpartum period, relatively more is
      stored in central vs. peripheral depots, resulting in a patterned change in body
      shape with parity.

PMID- 16596595
TI  - Life history, enamel formation, and linear enamel hypoplasia in the Ceboidea.
AB  - Linear enamel hypoplasia (LEH), a developmental defect of enamel, increases in
      frequency from prosimian to monkey to lesser ape to great ape grades (Guatelli
      Steinberg 2000 Am. J. Phys. Anthropol. 112:395-410, [2001] Evol. Anthropol.
      10:138-151; Newell 1998 Ph.D. dissertation, Temple University). This taxonomic
      pattern in the distribution of LEH is closely related to maturation length across
      the primate order (Newell 1998 Ph.D. dissertation, Temple University, 2000 Am. J.
      Phys. Anthropol. [Suppl.] 30:236). Longer maturation periods are associated with
      higher LEH frequencies; they appear to provide greater opportunity for defects to
      form. The present study explores the relationship between maturation length and
      LEH frequency within the Ceboidea. Because of its prolonged period of growth,
      Cebus is predicted to manifest LEH at a higher frequency than the more rapidly
      maturing ceboid genera. To test this hypothesis, two separate researchers (E.A.N.
      and D.G.-S.) examined LEH in nonoverlapping museum series of ceboids. The results
      support the hypothesis: in 13 genera (n = 1,276), E.A.N. found that LEH
      frequencies ranged from 0% in Callicebus, Cebuella, and Saimiri to 20% in Cebus.
      D.G.-S. found similar frequencies among five genera (n = 107), from 0% in Saimiri
      to 32% in Cebus. Thus, the broad pattern of LEH distribution evident across major
      taxonomic groups of primates is repeated within the Ceboidea. We also examined a
      related hypothesis linking the spacing of perikymata, which is influenced by
      enamel extension rates (Shellis 1998 J. Hum. Evol. 35:387-400), to LEH. The most
      likely areas of tooth crowns to exhibit LEH in human teeth are those in which
      perikymata are most closely spaced (Hillson and Bond 1997 Am. J. Phys. Anthropol.
      104:89-103). We hypothesized that the longer-maturing Cebus, with its elevated
      LEH frequency, will also exhibit more closely spaced perikymata than other
      ceboids. Analysis of a small microscopic subsample (n = 8) lends limited support
      to this second hypothesis.

PMID- 16596597
TI  - Stable isotopes and dietary adaptations in humans and animals at pre-pottery
      Neolithic Nevalli Cori, southeast Anatolia.
AB  - Human and animal bones from the Pre-Pottery Neolithic B site of Nevali Cori
      (southeast Anatolia) were analyzed with regard to stable carbon and nitrogen
      isotopes in bone collagen, and stable carbon and oxygen isotopes in bone
      carbonate. The reconstruction of the vertebrate food web at this site revealed
      that humans may have faced difficulties with meat procurement, since their stable
      isotope ratios reflect a largely herbivorous diet. This is in contrast with the
      preceding Pre-Pottery Neolithic A contexts and late Neolithic sites in the
      Fertile Crescent, where humans are located at the top of the food chain.
      Conceivably, Nevali Cori represents a community in the transition from a hunting
      and gathering subsistence to an economy with agriculture and animal husbandry,
      since domesticated einkorn and sheep, pigs, and probably also goats are in
      evidence at the site. In the second half of the 9th millennium calibrated (cal.)
      BC, however, the contribution of stock on the hoof to the human diet still seems
      modest. Animals kept under cultural control obviously had a dietary spectrum
      different from their free-ranging relatives. We conclude that these animals had
      been deliberately nourished by their owners, whereby the overall low delta(15)N
      signatures in both humans and livestock might result from the consumption of
      protein-rich pulses.

PMID- 16596598
TI  - Application of an image-based weighted measure of skeletal bending stiffness to
      great ape mandibles.
AB  - Traditional measures of structural stiffness in the primate skeleton do not
      consider the heterogeneous material stiffness distribution of bone. This
      assumption of homogeneity introduces an unknown degree of error in estimating
      stiffness in skeletal elements. Measures of weighted stiffness can be developed
      by including heterogeneous grayscale variations evident in computed tomographic
      (CT) images. Since gray scale correlates with material stiffness, the
      distribution of bone quality and quantity can be simultaneously considered. We
      developed weighted measures of bending resistance and applied these to CT images
      at three locations along the mandibular corpus in the hominoids Gorilla, Pongo,
      and Pan. We calculated the traditional (unweighted) moment of inertia for
      comparison to our weighted measure, which weighs each pixel by its gray-scale
      value. This weighing results in assignment of reduced moment of inertia values to
      sections of reduced density. Our weighted and unweighted moments differ by up to
      22%. These differences are not consistent among sections, however, such that they
      cannot be calculated by simple correction of unweighted moments. The effect of
      this result is that the rank ordering of individual sections within species
      changes if weighted moments are considered. These results suggest that the use of
      weighted moments may spur different interpretations of comparative data sets that
      rely on stiffness measures as estimates of biomechanical competence.

PMID- 16596599
TI  - Conformational effects on circular dichroism in the photoelectron angular
      distribution.
AB  - The B-spline density-functional method has been applied to the conformers of the
      (1R, 2R)-1,2-dibromo-1,2-dichloro-1,2-difluoroethane molecule. The cross section,
      asymmetry, and dichroic parameters relative to core and valence orbitals, which
      do not change their nature along the conformational curve, have been
      systematically studied. While the cross section and the asymmetry parameter are
      weakly affected, the dichroic parameter appears to be rather sensitive to the
      particular conformer of the molecule, suggesting that this dynamical property
      could be a useful tool for conformational analysis. The computational method has
      also been applied to methyl rotation in methyloxirane. Unexpected and dramatic
      sensitivity of the dichroic-parameter profile to the methyl rotation, both in the
      core and valence states, has been found. Boltzmann averaging over the conformers
      reproduces quite closely the profiles previously obtained for the minimum-energy
      conformation, which is in good agreement with the experimental results.

PMID- 16596600
TI  - Hunter-gatherer postcranial robusticity relative to patterns of mobility,
      climatic adaptation, and selection for tissue economy.
AB  - Human skeletal robusticity is influenced by a number of factors, including
      habitual behavior, climate, and physique. Conflicting evidence as to the relative
      importance of these factors complicates our ability to interpret variation in
      robusticity in the past. It remains unclear how the pattern of robusticity in the
      skeleton relates to adaptive constraints on skeletal morphology. This study
      investigates variation in robusticity in claviculae, humeri, ulnae, femora, and
      tibiae among human foragers, relative to climate and habitual behavior. Cross
      sectional geometric properties of the diaphyses are compared among hunter
      gatherers from southern Africa (n = 83), the Andaman Islands (n = 32), Tierra del
      Fuego (n = 34), and the Great Lakes region (n = 15). The robusticity of both
      proximal and distal limb segments correlates negatively with climate and
      positively with patterns of terrestrial and marine mobility among these groups.
      However, the relative correspondence between robusticity and these factors varies
      throughout the body. In the lower limb, partial correlations between polar second
      moment of area (J(0.73)) and climate decrease from proximal to distal section
      locations, while this relationship increases from proximal to distal in the upper
      limb. Patterns of correlation between robusticity and mobility, either
      terrestrial or marine, generally increase from proximal to distal in the lower
      and upper limbs, respectively. This suggests that there may be a stronger
      relationship between observed patterns of diaphyseal hypertrophy and behavioral
      differences between populations in distal elements. Despite this trend, strength
      circularity indices at the femoral midshaft show the strongest correspondence
      with terrestrial mobility, particularly among males.

PMID- 16596602
TI  - Continuity of interpersonal violence between Nubian communities.
AB  - Modern communities affiliated with the same culture have been shown to experience
      comparable levels of interpersonal violence, no matter what their size. It was
      hypothesized that a similar relationship would exist among ancient rural and
      urban people, but that accident-related trauma may be more prominent among rural
      dwellers due to their activity base. Through an analysis of antemortem trauma,
      this investigation contrasted the injury profile of Nubian adult villagers (N =
      55) from the Kerma period (2500-1750 BC) to that of their urban neighbors (N =
      223) at Kerma (2050-1500 BC). The injury pattern associated with interpersonal
      violence (cranial injury, direct-force ulna fractures, and multiple injuries) was
      similar between the two samples, as hypothesized. The rural group sustained
      significantly more nonviolence-related injuries that suggested occupational or
      environmental influences. The more severe cranial injuries observed among urban
      people are attributed to a preference for more lethal hand-wielded objects that
      may have accompanied increasing local tensions and incursions into Egypt during
      the 17th Dynasty.

PMID- 16596603
TI  - Brief communication: identification of the authentic ancient DNA sequence in a
      human bone contaminated with modern DNA.
AB  - We present a method to distinguish authentic ancient DNA from contaminating DNA
      in a human bone. This is achieved by taking account of the spatial distribution
      of the various sequence families within the bone and the extent of degradation of
      the template DNAs, as revealed by the error content of the sequences. To
      demonstrate the veracity of the method, we handled two ancient human tibiae in
      order to contaminate them with modern DNA, and then subjected segments of the
      bones to various decontaminating treatments, including removal of the outer 1-2
      mm, before extracting DNA, cloning, and obtaining a total of 107 mitochondrial
      DNA sequences. Sequences resulting from the deliberate contamination were located
      exclusively in the outer 1-2 mm of the bones, and only one of these 27 sequences
      contained an error that could be ascribed to DNA degradation. A second, much
      smaller set of relatively error-free sequences, which we ascribe to contamination
      during excavation or curation, was also located exclusively in the outer 1-2 mm.
      In contrast, a family of 72 sequences, displaying extensive degradation products
      but identifiable as haplogroup U5a1a, was distributed throughout one of the bones
      and represents the authentic ancient DNA content of this specimen.

PMID- 16596604
TI  - Recent progress in ultrafast X-ray diffraction.
AB  - X-ray diffraction with femtosecond time-resolution represents a direct probe of
      ultrafast structural changes in condensed matter. The generation of ultrashort X
      ray pulses in laser-driven plasma and/or accelerator-based sources has made
      substantial progress, and has allowed for studies of transient structures with an
      unprecedented accuracy. Herein, recent work on transient crystalline structures
      is reviewed, with the focus on laser-based experiments.

PMID- 16596605
TI  - Ontogeny of facial dimorphism and patterns of individual development within one
      human population.
AB  - Based on a longitudinal study of radiographs of the Denver Growth Study, we
      investigated the morphological development of individual and gender differences
      in the anterior neurocranium, face, and basicranium. In total, 500 X-rays of 14
      males and 14 females, each with 18 landmarks and semilandmarks, were digitized
      and analyzed using geometric morphometric methods. Sexual dimorphism in shape and
      form is already present at the earliest age stage included in the analysis.
      However, the nature of dimorphism changes with age. Four factors apper to
      contribute to cranial sexual dimorphism in human postnatal development: 1)
      initial, possibly prenatal, differences in shape; 2) differences in the
      association of size and shape; 3) male hypermorphosis; and 4) some degree of
      difference in the direction of male and female growth trajectories. Studying
      changes in individuals, we find a low correlation between newborn and adult
      morphology, while 3-year-olds already show a high correlation with their adult
      form. We conclude that the adult pattern of interindividual difference in facial
      form in a single human population is established within the first few years of
      life.

PMID- 16596608
TI  - Ultrafast chronoamperometry of single impact events in acoustically agitated
      solid particulate suspensions.

PMID- 16596606
TI  - Comment on "Disproving a silicon analog of an alkyne with the aid of topological
      analyses of the electronic structure and ab initio molecular dynamics
      calculations".

PMID- 16596610
TI  - Highly anisotropic orbitally dependent superexchange in cyano-bridged clusters
      containing Mn(III) and Mn(II) ions.
AB  - We study the orbitally dependent magnetic exchange in cyanide-based clusters as a
      source of the barrier for reversal magnetization. We consider the Mn(III)-CN
      Mn(II) dimer and linear Mn(II)-NC-Mn(III)-CN-Mn(II) trimer containing
      octahedrally coordinated Mn(III) and Mn(II) ions with special emphasis on the
      magnetic manifestations of the orbital degeneracy of the Mn(III) ion. The kinetic
      exchange mechanism involves the electron transfer from the single occupied t(2)
      orbitals of the Mn(II) ion [6A1(t2(3)e2) ground state] to the singly occupied
      t(2) orbitals of the Mn(III) ion [3T1(t2(4)) ground state] resulting in the
      charge-transfer 5T2(t2(2)e2)Mn(III) - 2T2(t2(5))Mn(II) state of the pair. The
      deduced effective exchange Hamiltonian that takes into account orbital degeneracy
      leads to an essentially non-Heisenberg energy pattern. The energy levels are
      shown to be dependent on both spin and orbital quantum numbers, thus providing
      direct information about the magnetic anisotropy of the system. Along with the
      magnetic exchange, the model includes an axial component of the crystal field and
      spin-orbit coupling operating within the ground 3T1(t2(4)) cubic term of the
      Mn(III) ion. We have shown that under certain conditions both named interactions
      lead to the occurrence of the barrier for the reversal of magnetization, which
      significantly increases when passing from the dimer to the trimer. This provides
      a possible way for raising the magnetic barrier in the family of cyano-bridged
      manganese clusters.

PMID- 16596609
TI  - Design of improved deep eutectic solvents using hole theory.

PMID- 16596611
TI  - The "non-reaction" of ground-state triplet carbon atoms with water revisited.
AB  - We introduce a novel experimental setup for the generation of carbon atoms by
      means of pulsed laser ablation with a pulse rate optimized to avoid warming of
      the matrix. The combination of this technique with annealing of the matrix,
      recooling, and spectral recording (e.g. IR) allowed us to differentiate between
      the reactivity of triplet and singlet carbon atoms towards water under matrix
      isolation conditions. Our experimental procedure assures the relaxation of all
      unreacted carbon atoms to their triplet ground state in the 10 K matrix before
      spectral recording. In agreement with CCSD(T)/cc-pVTZ+ZPVE computational data and
      earlier lower level results, we find that triplet carbon atoms indeed do not
      react with water, despite their high initial energy. Intersystem crossing of the
      triplet to singlet states of hydroxy carbene are less important, as the barriers
      for rearrangement of the initial complex of triplet carbon atoms and water to
      covalently bound species are too high, and dissociation is more likely. We found
      no evidence for a direct O--H bond-insertion path for triplet carbon atoms. Self
      condensation reactions of triplet carbon atoms are clearly favored and yield
      carbon clusters that show reactivity of their own. The proposed formation of
      aldoses in extraterrestrial environments can therefore only derive from "hot"
      carbon atoms or through photoreactions.

PMID- 16596612
TI  - Fingerprints of damped quantum rotation observed in solid-state proton NMR
      spectra.
AB  - (1)H NMR spectra of the methyl group in an oriented crystal sample of
      methylmalonic acid with all three non-methyl protons replaced by deuterons are
      interpreted in terms of the damped quantum rotation (DQR) theory of NMR line
      shapes. The DQR approach offers a perfect theoretical reproduction of the
      observed spectra while the conventional Alexander-Binsch line-shape model shows
      evident defects in the present case. The temperature trends of the quantities
      characterizing the coherent and incoherent dynamics of the methyl group in the
      DQR approach (the effective tunnelling frequency and two coherence-damping rates)
      derived from the spectra are fairly reproduced using a model reported previously.
      The present findings provide further evidence of limitations to the validity of
      the common belief that molecular rate processes in condensed phases are
      necessarily classical.

PMID- 16596613
TI  - Alternative low-energy mechanisms for isotopic exchange in gas-phase D2O-H+(H2O)n
      reactions.
AB  - Molecular-dynamics (MD) trajectories and high-level ab initio methods have been
      used to study the low-energy mechanism for D(2)O-H(+)(H(2)O)(n) reactions. At low
      collisional energies, MD simulations show that the collisional complexes are long
      lived and undergo fast monomolecular isomerization, converting between different
      isomers within 50-500 ps. Such processes, primarily involving water-molecule
      shifts along a water chain, require the surmounting of very-low-energy barriers
      and present sizable non- Rice-Ramsperger-Kassel-Marcus (RRKM) effects, which are
      interpreted as a lack of randomization of the internal kinetic energy.
      Interestingly, the rate of water shifts was found to increase upon increasing the
      size of the cluster. Based on these findings, we propose to incorporate the
      following steps into the mechanism for low-energy isotopic scrambling these D(2)O
      H(+)(H(2)O)(n) reactions: a) formation of the collisional complex
      [H(+)(H(2)O)(n)D(2)O]* in a vibro-rotational excited state; b) incorporation of
      the heavy-water molecule in the cluster core as HD(2)O(+) by means of
      isomerization involving molecular shifts; c) displacement of solvation molecules
      from the first shell of HD(2)O(+) inducing de-deuteration (shift of a D(+) to a
      neighbor water molecule); d) reorganization of the clusters and/or expulsion of
      one of the isotopic variants of water (H(2)O, HDO or D(2)O) from the periphery of
      the complex.

PMID- 16596614
TI  - Kinetic model of energy transfer processes between low-coordinated ions on MgO by
      photoluminescence decay measurements.
AB  - Photoluminescence decay studies of emitting species on MgO nanocubes at room
      temperature provide evidence of three surface species characterized by an
      excitation and emission wavelength couple {lambda(exc);lambda(em)}. Species A
      corresponds to {lambda(exc)=240 nm; lambda(em)=380 nm}, whereas the couple
      {lambda(exc)=280 nm; lambda(em)=470 nm} is assigned to two species: B and B', the
      former is involved in energy transfer from excited state A* and the latter in
      direct emission from excited state B'*. A simple model for energy transfer from
      species A* to B is proposed. The numerical resolution of equations corresponding
      to this model is in good agreement with experimental data. This method quantifies
      the kinetics of intrinsic emission and energy transfer processes. Lifetime values
      indicate that phosphorescence is taking place, and species A, B and B' are
      identified as edge O(2-) (4 C), corner O(2-) (3 C) and kink O(2-) (3 C) oxide
      ions respectively.

PMID- 16596615
TI  - Linked crystallites in the conducting topmost layer of polymer bilayer films
      controlled by temperature: from micro- to nanocrystallites.
AB  - Temperature has great impact on the structure and size of the linked crystallites
      of the conducting topmost layer formed at the surface of a polycarbonate film via
      the reaction BEDT-TTF+IBr [BEDT-TTF=bis(ethylenedithio)tetrathiafulvalene]. We
      show that fine temperature control permits formation of a semiconducting topmost
      layer of alpha'-(BEDT-TTF)(2)(I(x)Br(1-x))(3) crystallites with either micro- or
      nanometre size, a result that opens a route to miniaturized conducting plastic
      materials.

PMID- 16596616
TI  - Spin-orbit ab initio investigation of the photolysis of bromoiodomethane.
AB  - The photodissociation of bromoiodomethane has been investigated by spin-orbit ab
      initio calculations. The experimentally observed A- and B-bands and the
      corresponding photoproducts were assigned by multistate second-order
      multiconfigurational perturbation theory in conjunction with spin-orbit
      interaction through complete active space state interaction potential energy
      curves, vertical excitation energies, and oscillator strengths of low-lying
      excited states. The present conclusions with respect to the dissociation process
      in the B-band are different compared with those of previous studies. The reaction
      between the iso-CH(2)Br-I and iso-CH(2)I-Br species has also been studied.
      Finally, a set of stable excited states was identified for both isomers. These
      species might be of importance in the recombination process that follows the
      photodissociation in a solvent.

PMID- 16596617
TI  - Combined permutation test and mixed-effect model for group average analysis in
      fMRI.
AB  - In group average analyses, we generalize the classical one-sample t test to
      account for heterogeneous within-subject uncertainties associated with the
      estimated effects. Our test statistic is defined as the maximum likelihood ratio
      corresponding to a Gaussian mixed-effect model. The test's significance level is
      calibrated using the same sign permutation framework as in Holmes et al.,
      allowing for exact specificity control under a mild symmetry assumption about the
      subjects' distribution. Because our likelihood ratio test does not rely on
      homoscedasticity, it is potentially more sensitive than both the standard t test
      and its permutation-based version. We present results from the Functional Imaging
      Analysis Contest 2005 dataset to support this claim.

PMID- 16596618
TI  - Permutation testing of orthogonal factorial effects in a language-processing
      experiment using fMRI.
AB  - The block-paradigm of the Functional Image Analysis Contest (FIAC) dataset was
      analysed with the Brain Activation and Morphological Mapping software.
      Permutation methods in the wavelet domain were used for inference on cluster
      based test statistics of orthogonal contrasts relevant to the factorial design of
      the study, namely: the average response across all active blocks, the main effect
      of speaker, the main effect of sentence, and the interaction between sentence and
      speaker. Extensive activation was seen with all these contrasts. In particular,
      different vs. same-speaker blocks produced elevated activation in bilateral
      regions of the superior temporal lobe and repetition suppression for linguistic
      materials (same vs. different-sentence blocks) in left inferior frontal regions.
      These are regions previously reported in the literature. Additional regions were
      detected in this study, perhaps due to the enhanced sensitivity of the
      methodology. Within-block sentence suppression was tested post-hoc by regression
      of an exponential decay model onto the extracted time series from the left
      inferior frontal gyrus, but no strong evidence of such an effect was found. The
      significance levels set for the activation maps are P-values at which we expect
      <1 false-positive cluster per image. Nominal type I error control was verified by
      empirical testing of a test statistic corresponding to a randomly ordered design
      matrix. The small size of the BOLD effect necessitates sensitive methods of
      detection of brain activation. Permutation methods permit the necessary
      flexibility to develop novel test statistics to meet this challenge.

PMID- 16596620
TI  - Mesoblastic nephroma--a report from the Gesellschaft fur Padiatrische Onkologie
      und Hamatologie (GPOH).
AB  - BACKGROUND: Surgery alone is the appropriate first-line treatment for patients
      with mesoblastic nephroma (MN). Nevertheless, there are reports of local
      recurrences and metastasis, especially in the cellular subtype. The authors
      evaluated the outcome of patients with MN who were enrolled in either the
      International Society of Pediatric Oncology (SIOP) 93-01/GPOH or the SIOP
      2001/GPOH Nephroblastoma Study and Trial. METHODS: In total, 50 patients with MN
      were analyzed. Eleven patients were suspected antenatally of having a renal
      tumor. The median age at diagnosis was 18.5 days. Central pathologic review was
      performed for all specimens. The median observation time was 4.2 years. RESULTS:
      Forty-five patients underwent initial surgery. Five patients older than 6 months
      received preoperative chemotherapy. Twenty-nine tumors were classic MN, and 21
      tumors were cellular MN. Nine patients had a Stage III MN, 5 of those patients
      had tumor ruptures, and 8 had positive surgical margins. After they underwent
      nephrectomy, 40 patients received no further treatment. For the entire group,
      event-free survival (EFS) (94%) and overall survival (OS) (95%) were excellent.
      Patients with a cellular MN, patients with age 3 months or older, and patients
      with Stage III MN had lower EFS. Three patients developed recurrent disease, and
      2 of those patients died. Metastases to the brain, lung, and liver were observed
      in 1 patient. CONCLUSIONS: Radical nephrectomy with accurate surgical-pathologic
      staging is the standard of care for children with MN. Nonetheless, a subgroup of
      patients with MN (Stage III cellular MN in patients age 3 months or older) tends
      to develop recurrences more often. Further prospective studies will be needed to
      verify this finding and should help determine whether these patients may benefit
      from adjuvant therapy.

PMID- 16596619
TI  - Phosphorylation regulates Myc expression via prolonged activation of the mitogen
      activated protein kinase pathway.
AB  - We previously showed that prolonged and strong ERK phosphorylation induced by
      Compound 5 (Cpd 5), a Cdc25A protein phosphatase inhibitor, was involved in its
      mechanism of cell growth inhibition. To study the relationship between ERK
      phosphorylation and cell growth inhibition, we used Cpd 5 as a tool to
      investigate ERK-regulated c-Myc expression in Hep3B hepatoma cells. We found that
      ERK phosphorylation caused by Cpd 5 induced c-Myc phosphorylation, but suppressed
      c-Myc expression at the mRNA and protein levels. Furthermore, Cpd 5 inhibited c
      Myc transcriptional activity and DNA binding ability, and this inhibition was
      antagonized by ERK kinase (MEK) inhibitor U-0126, implying that the ERK pathway
      was involved in regulating c-Myc expression. Since the participation of c-Myc
      protein in transcription requires its dimerization with Max protein, we examined
      the Myc-Max association in Cpd 5-treated cells and found that Cpd 5 suppressed
      Myc-Max dimerization. Transfection of Hep3B cells with mutated ERK (T188A/Y190F),
      which has lost its dual-phosphorylation sites, attenuated the actions of Cpd 5 on
      Myc-Max association. To further demonstrate whether Myc phosphorylation by Cpd 5
      induced ERK activation was able to directly regulate c-myc gene expression, a
      chromatin immunoprecipitation (ChIP) assay was used to examine the binding of
      phospho-Myc to the c-myc promoter region. We found that phospho-Myc induced by
      Cpd 5 had lost its ability to bind to the c-myc promoter, whereas MEK inhibitor U
      0126 antagonized this inhibitory effect. These data suggest that an increase in c
      Myc phosphorylation in response to prolonged ERK phosphorylation negatively auto
      regulates c-Myc gene expression, leading to the suppression of its target gene
      expression and cell cycle block.

PMID- 16596621
TI  - Evaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast
      cancer vaccine trial.
AB  - BACKGROUND: E75 and GP2 are human leukocyte antigen (HLA)-A2-restricted
      immunogenic peptides derived from the HER2/neu protein. In a E75 peptide-based
      vaccine trial, preexisting immunity and epitope spreading to GP2 was detected.
      The purpose of this study was to further investigate GP2 for potential use in
      vaccination strategies. Importantly, a naturally occurring polymorphism (I-->V at
      position 2, 2VGP2) associated with increased breast cancer risk was addressed.
      METHODS: Prevaccination peripheral blood samples (PBMC) from HLA-A2 breast cancer
      patients and CD8+ T cells from HLA-A2 healthy donors were stimulated with
      autologous dendritic cells (DC) pulsed with GP2 and tested in standard
      cytotoxicity assays with HER2/neu+ tumor cells or GP2- or 2VGP2-loaded T2
      targets. Additional cytotoxicity experiments used effectors stimulated with DC
      pulsed with E75, GP2, or the combination of E75+GP2. RESULTS: GP2-stimulated
      prevaccination PBMC from 28 patients demonstrated killing of MCF-7, SKOV3-A2, and
      the HLA-A2- control target SKOV3 of 28.8+/-3.7% (P<.01), 29.5+/-4.0% (P<.01), and
      16.9+/-2.7%, respectively. When compared with E75, GP2-stimulated CD8+ T cells
      lysed HER2/neu+ targets at 43.8+/-5.2% versus 44.2+/-5.7% for E75 (P=.87). When
      combined, an additive effect was noted with 58.6+/-5.4% lysis (P=.05). GP2
      stimulated CD8+ T cells specifically recognized both GP2-loaded (19.6+/-5.7%) and
      2VGP2-loaded T2 targets (17.7+/-5.2%). CONCLUSIONS: GP2 is a clinically relevant
      HER2/neu-derived peptide with immunogenicity comparable to that of E75.
      Importantly, GP2-specific effectors recognize 2VGP2-expressing targets;
      therefore, a GP2 vaccine should be effective in patients carrying this
      polymorphism. GP2 may be most beneficial used in a multiepitope vaccine.

PMID- 16596622
TI  - Particle embolization of recurrent hepatocellular carcinoma after hepatectomy.
AB  - BACKGROUND: Complete surgical resection is the mainstay of treatment for patients
      with hepatocellular carcinoma (HCC). Unfortunately, most patients ultimately
      develop disease recurrence and the median survival from the time of recurrence is
      <1 year. The purpose of the current study was to review the authors' experience
      using bland hepatic arterial embolization to treat recurrent HCC after definitive
      surgical resection. METHODS: The authors reviewed their single-center hepatic
      embolization database from 1995 through 2004 to identify patients who underwent
      bland hepatic arterial embolization for disease recurrence. Data analyzed
      included patient demographics, Okuda stage and Child score, imaging findings, and
      embolization variables. Recurrence-free survival (from surgery to disease
      recurrence) and survival time (from recurrence to last follow-up) were calculated
      using the Kaplan-Meier method. RESULTS: The authors identified 45 patients
      treated with bland embolization for recurrent HCC after resection. Six patients
      also underwent ablative therapy after embolization. Of the 45 patients, 42
      (93.3%) patients had Okuda Stage 1 disease. The median time to recurrence was 13
      months. The median survival after embolization was 46 months, and actuarial
      survival rates at 1 year, 2 years, and 5 years after recurrence were 86%, 74%,
      and 47%, respectively, with a median follow-up of 31 months. Patients who
      developed disease recurrence with a solitary lesion had a significantly improved
      survival (P = .03) At the time of last follow-up, 3 patients (6.6%) were alive
      with no evidence of viable disease. CONCLUSIONS: Bland arterial embolization was
      found to be an effective method of salvage therapy for patients with good liver
      function with recurrent HCC after prior surgical resection. Patients whose
      disease recurred with a solitary lesion appear to have a significantly increased
      survival compared with patients who develop disease recurrence with multiple
      tumors. A small proportion of patients can be rendered without evidence of viable
      disease.

PMID- 16596623
TI  - Effects of repeated phencyclidine administration on adult hippocampal
      neurogenesis in the rat.
AB  - Dysfunctional maturation of neural networks, particularly hippocampus-prefrontal
      networks, may be of particular interest in determining the pathophysiology of
      schizophrenia. Phencyclidine (PCP)-induced symptoms in humans appear to offer a
      more complete model of schizophrenia than do amphetamine-induced symptoms. This
      study investigated the effects of intermittent i.p. injections of PCP (7.5 mg/kg)
      on cell proliferation and survival of granule cells in the dentate gyrus of the
      rat brain using quantitative immunohistochemical techniques for 5-bromo-2'
      deoxyuridine (BrdU)-positive cells. After repeated PCP injection for 14 days,
      mean scores for stereotyped behavior increased with the number of injections,
      while scores for ataxia and backpedaling as serotonergic behaviors gradually
      decreased. The number of BrdU-positive cells decreased by 23% in the subgranular
      zone of the dentate gyrus by 24 h after repeated injections. However, decreased
      levels of BrdU-positive cells returned to control levels within 1 week.
      Differentiation of newly formed cells was not influenced. Repeated PCP
      administration after BrdU injection did not exert any effects on survival of
      newly generated cells. These findings suggest that transient disturbances of cell
      proliferation in the dentate gyrus occur under PCP-related behavioral
      abnormalities. Whether disturbed cell proliferation would thus be closely
      implicated in the development of behavioral sensitization induced by PCP
      administration is unclear, but this would possibly result from adaptation to new
      pharmacological conditions under behavioral sensitization or stressful conditions
      of PCP-related abnormal behaviors. Further studies are required to elucidate the
      biological significance of hippocampal neurogenesis in the mechanisms underlying
      the development of cognitive dysfunctions and the psychosis of schizophrenia.

PMID- 16596624
TI  - Increased tryptophan hydroxylase immunoreactivity in the dorsal raphe nucleus of
      alcohol-dependent, depressed suicide subjects is restricted to the dorsal
      subnucleus.
AB  - Considerable evidence suggests that alcoholics with co-occurring depressive
      disorder are at greater risk for developing psychosocial problems particularly
      suicidal behavior. Moreover, dysfunction in serotonin (5-HT) neurotransmission
      has been implicated in depression, suicide and alcoholism. In the present study,
      we measured the levels of tryptophan hydroxylase (TPH), the main synthetic enzyme
      of 5-HT synthesis, in specific nuclei of the dorsal raphe (DR) in depressed
      suicide victims with alcohol dependence and matched psychiatrically normal
      controls. TPH immunoreactivity (IR) was quantified in frozen tissue sections
      containing the DR from 8 suicide victims with a diagnosis of major depression and
      alcohol dependence, and 8 psychiatrically normal control subjects by using
      immunoautoradiographic methods. We found that the levels of TPH-IR were
      significantly increased by 46% in the dorsal subnucleus of the DR in depressed
      suicide victims with alcohol dependence when compared with controls. In contrast,
      TPH-IR levels did not significantly differ in the other DR subnuclei between
      depressed, alcoholic suicide subjects, and controls. Our results indicate that
      abnormalities in 5-HT biosynthesis in the brain of depressed alcoholic suicide
      subjects are restricted within distinct regions of the DR.

PMID- 16596625
TI  - Excitatory actions of the ventral midline thalamus (rhomboid/reuniens) on the
      medial prefrontal cortex in the rat.
AB  - The medial prefrontal cortex (mPFC) has been associated with diverse functions
      including attentional processes, visceromotor activity, decision making, goal
      directed behavior, and working memory. The present report examined the effects of
      stimulation of the midline thalamus, concentrating on ventral nuclei of the
      midline thalamus, on evoked activity at the mPFC. The nucleus reuniens (RE) of
      the ventral midline thalamus is a major source of projections to the hippocampus
      and to the mPFC, and has been shown to exert pronounced excitatory effects on the
      hippocampus. No previous study has systematically examined the actions of the
      ventral midline thalamus on the mPFC. We showed that stimulation of the dorsal
      and ventral midline thalamus, but not of an intermediate region lying between
      them (null zone), produced short latency, large amplitude evoked potentials
      throughout the dorsoventral extent of the medial PFC. The largest effects were
      elicited with ventral midline stimulation (rhomboid/reuniens nuclei) at the
      ventral mPFC--the prelimbic (PL) and infralimbic (IL) cortices. Specifically,
      stimulation of RE produced evoked potentials (early negative component, N2) at
      the PL cortex at a mean latency of 22.6 msec and mean amplitude of 0.85 mV,
      indicative of monosynaptic effects. In addition, we showed that paired pulse
      stimulation of RH/RE produced strong facilitatory actions (paired pulse
      facilitation) at IL (83%) and PL (75%). These findings indicate that RE exerts
      strong direct excitatory effects on the mPFC, and coupled with the demonstration
      that RE produces similar actions on the hippocampus, indicates that RE is in a
      position to influence and possibly coordinate the activity of these two forebrain
      structures subserving memory.

PMID- 16596626
TI  - Population dynamics and in situ kinetics of nitrifying bacteria in autotrophic
      nitrifying biofilms as determined by real-time quantitative PCR.
AB  - Population dynamics of ammonia-oxidizing bacteria (AOB) and uncultured Nitrospira
      like nitrite-oxidizing bacteria (NOB) dominated in autotrophic nitrifying
      biofilms were determined by using real-time quantitative polymerase chain
      reaction (RTQ-PCR) and fluorescence in situ hybridization (FISH). Although two
      quantitative techniques gave the comparable results, the RTQ-PCR assay was easier
      and faster than the FISH technique for quantification of both nitrifying bacteria
      in dense microcolony-forming nitrifying biofilms. Using this RTQ-PCR assay, we
      could successfully determine the maximum specific growth rate (mu = 0.021/h) of
      uncultured Nitrospira-like NOB in the suspended enrichment culture. The
      population dynamics of nitrifying bacteria in the biofilm revealed that once they
      formed the biofilm, the both nitrifying bacteria grew slower than in planktonic
      cultures. We also calculated the spatial distributions of average specific growth
      rates of both nitrifying bacteria in the biofilm based on the concentration
      profiles of NH4+, NO2-, and O2, which were determined by microelectrodes, and the
      double-Monod model. This simple model estimation could explain the stratified
      spatial distribution of AOB and Nitrospira-like NOB in the biofilm. The
      combination of culture-independent molecular techniques and microelectrode
      measurements is a very powerful approach to analyze the in situ kinetics and
      ecophysiology of nitrifying bacteria including uncultured Nitrospira-like NOB in
      complex biofilm communities.

PMID- 16596627
TI  - Regulation of conceptus adhesion by endometrial CXC chemokines during the
      implantation period in sheep.
AB  - To gain a better understanding of biochemical mechanisms of conceptus adhesion to
      the maternal endometrium in ruminant ungulates, the present study was performed
      to clarify roles of chemokines and extracellular matrix (ECM) components in the
      regulation of ovine blastocyst attachment to the endometrium. In addition to the
      chemokine, interferon-gamma inducible protein 10 kDa (IP-10, CXCL10), the
      chemokine receptor, CXCR3, also recognizes two other chemokines; monokine induced
      by IFN-gamma (MIG, CXCL9) and IFN-inducible T cell alpha chemoattractant (I-TAC,
      CXCL11). Similar to CXCL10, CXCL9, and CXCL11 were expressed in the uterus during
      the peri-implantation period, and CXCL9 mRNA expression was stimulated in
      endometrial explants from day 14 cyclic ewes by the addition of IFN-tau or IFN
      gamma. Without ECM components, conceptus cell adhesion was low on day 14 of
      gestation and exhibited a 2.5-fold increase on day 17; adhesiveness on day 20 was
      1/10 of that on day 14. Among various ECM components examined, trophoblast
      adhesion was greatest when fibronectin was used. Although day 14 conceptuses did
      not show much adhesive activity to fibronectin, day 17 trophoblast, and day 20
      chorionic membrane exhibited 2.3-fold and 50-fold increase, respectively, which
      was enhanced by treatment with CXCL9 or CXCL10. These results indicate that
      through endometrial fibronectin and chemokines, ovine conceptus cells gain the
      ability to attach to the endometrium during pre-implantation period; however,
      elucidation of molecular mechanisms by which the conceptus acquires the adhesive
      ability during this time period awaits further investigation.

PMID- 16596628
TI  - Effect of sperm DNA vaccine on fertility of female mice.
AB  - Our laboratory has identified a sperm-specific dodecamer peptide sequence,
      designated as YLP(12), vaccination with which causes a long-term reversible
      immunocontraceptive effect in female mice. In the present study, the effects of
      YLP(12) DNA vaccine were examined. YLP(12) 36 bp cDNA was cloned into pVAX1
      vector to prepare the DNA vaccine. Two additional vaccine constructs were made by
      in frame cloning of one and two CpG repeats in the YLP(12)-cDNA vaccine. Five
      groups of female mice were immunized intradermally by using gene gun with YLP(12)
      cDNA, YLP(12)-cDNA-CpG, YLP(12)-cDNA-CpG-CpG, YLP(12)-cDNA mixed with exogenous
      synthetic CpG oligodeoxynucleotide (ODN), or vector DNA alone, respectively.
      Vaccination with all three constructs and the YLP(12) vaccine mixed with
      exogenous ODN raised antibody response both in the sera as well as locally in the
      vaginal tract. There was no antibody response in the mice injected with the
      vector alone. In sera, the highest titers were obtained for the IgG class for all
      constructs and formulation followed by IgA class. In vaginal washings the highest
      titers were obtained for the IgA class followed by IgG class. Within the IgG
      class, the titers for the IgG2a subclass were significantly greater than the IgG1
      subclass. Immunization with all constructs and formulation caused a significant
      (P < 0.05 to <0.001) reduction (20-43%) in fertility of female mice. The highest
      reductions were seen in mice immunized with YLP(12)-cDNA-CpG-CpG (two repeats)
      (43% reduction) and with the YLP(12) vaccine administered with exogenous CpG ODN
      (42% reduction). T lymphocytes obtained from DNA-vaccinated mice showed clearly
      distinguished comparative RT-PCR analysis of cytokine mRNA expression for Th1 and
      Th2 immune responses compared to T lymphocytes obtained from control animals
      injected with vector DNA. Expression of both Th1 cytokines (IL-2 and IFN-gamma)
      and Th2 cytokines (IL-4 and IL-10) was enhanced after DNA vaccination as compared
      to controls, with a bias towards Th1 response. The immunocontraceptive effects
      were long-lasting observed up to 1.3 years of the observation period and
      increased with time. These novel findings indicate that the intradermal
      immunization with a sperm-specific DNA vaccine causes a long-term circulating and
      local immune response resulting in immunocontraceptive effects in female mice.

PMID- 16596629
TI  - Unaliasing lipid contamination for MR spectroscopic imaging of gliomas at 3T
      using sensitivity encoding (SENSE).
AB  - 3D magnetic resonance spectroscopic imaging (MRSI) has been successfully employed
      to extract information about brain tumor metabolism, such as cell membrane
      breakdown, cellular energetics, and neuronal integrity, through its ability to
      differentiate signals coming from choline (Cho), creatine (Cr), and N-acetyl
      aspartate (NAA) molecules. The additional presence of lipids within subregions of
      the tumor may indicate cellular membrane breakdown due to cell death. Another
      potential source of lipids is subcutaneous fat, which may be excited with point
      resolved spectroscopy (PRESS) volume selection and aliased into the spectral
      field of view (FOV) due to the chemical shift artifact and the low bandwidth of
      the selection pulses. The purpose of our study was to employ a postprocessing
      method for unaliasing lipid resonances originating from in-slice subcutaneous
      lipids from the 3D MRSI of gliomas at 3T, using an eight-channel phased-array
      coil and sensitivity encoding (SENSE).

PMID- 16596630
TI  - In vivo quantitative three-dimensional motion mapping of the murine myocardium
      with PC-MRI at 17.6 T.
AB  - This work presents a method that allows for the assessment of 3D murine
      myocardial motion in vivo at microscopic resolution. Phase-contrast (PC) magnetic
      resonance imaging (MRI) at 17.6 T was applied to map myocardial motion in healthy
      mice along three gradient directions. High-resolution velocity maps were acquired
      at three different levels in the murine myocardium with an in-plane resolution of
      98 mum, a slice thickness of 0.6 mm, and a temporal resolution of 6 ms. The
      applied PC-MRI method was validated with phantom experiments that confirmed the
      correctness of the method with deviations of <1.7%. Myocardial in-plane
      velocities between 0.5 cm/s and 2.2 cm/s were determined for the healthy murine
      myocardium. Through-plane velocities of 0.1-0.83 cm/s were measured. Velocity
      data was also used to calculate the myocardial twist angle during systole at
      different slices in the short-axis view.

PMID- 16596631
TI  - Tektin 4 is located on outer dense fibers, not associated with axonemal tubulins
      of flagella in rodent spermatozoa.
AB  - Tektins, which are thought to be the constitutive proteins of microtubules in
      cilia, flagella, basal bodies, and centrioles, have been reported to be involved
      in the stability and structural complexity of axonemal microtubules. Four types
      of mammalian Tektins have been reported, and at least two types of Tektins,
      Tektin 2 and Tektin 4, have been verified to be present in sperm flagella. To
      elucidate the molecular localization of Tektin 4 in flagella of rodent
      spermatozoa, we performed immunocytochemistry, fractionation study followed by
      immunoblot analysis, and immunogold electron microscopy. Confocal laser scanning
      microscopy and immunogold electron microscopy indicated that Tektin 4 was
      associated with outer dense fibers (ODFs) in both the middle and principal piece
      of flagella in rat and mouse spermatozoa. Tektin 4 in rat spermatozoa is
      completely released by 6 M urea treatment, but not extracted by 1% Triton X-100
      and 0.6 M potassium thiocyanate. Pre-embedding immunoelectron microscopy
      demonstrated that Tektin 4 located on the abaxial (convex) surface of ODFs in
      flagella, not associate with axonemal microtubules. Our data strongly suggested
      that Tektin 4 is not associated with axonemal tubulins but an ODFs-affiliated
      molecule in rodent spermatozoa.

PMID- 16596632
TI  - Quantification of cerebral arterial blood volume using arterial spin labeling
      with intravoxel incoherent motion-sensitive gradients.
AB  - Quantification of cerebral arterial blood volume (CBVa) is important for
      understanding vascular regulation. To enable measurement of CBVa with diffusion
      weighted (DW) arterial spin labeling (ASL), a theoretical framework was developed
      using the effects of intravoxel incoherent motion (IVIM). The pseudo-diffusion
      coefficient (D*) in the IVIM model was evaluated at 9.4 T in DW-ASL of rat brain
      under isoflurane anesthesia by variations of both post-labeling delay (w) and
      magnetization transfer ratio (MTR). D* and its volume fraction decreased at
      values of w>or=0.3 s, and the normalized apparent diffusion coefficient (ADC)
      increased with MTR, suggesting that D* is closely correlated with CBVa. Thus, the
      difference between ASL measurements with and without DW gradients is related to
      CBVa. The CBVa values measured by this approach were compared with values
      obtained using the modulation of tissue and vessel (MOTIVE) technique with ASL,
      which varies MT levels without changing spin labeling efficiency. CBVa values
      from both methods were highly correlated. The measured CBVa values were linearly
      correlated with cerebral blood flow (CBF) for a PaCO2 range of 25-50 mmHg;
      DeltaCBVa (ml/100 g)=0.007 (min-1)xDeltaCBF (ml/100 g/min). The DW-ASL approach
      is simple and easy to implement for human and animal CBVa studies.

PMID- 16596633
TI  - Study of the polyol pathway in the porcine epididymis.
AB  - Concentrations of D-glucose, D-fructose and D-sorbitol were quantified in porcine
      epididymal fluid by spectrofluorimetric assays and aldose reductase (AR) and
      sorbitol dehydrogenase (SDH) were located immunohistochemically in the epididymal
      epithelium. Glucose and fructose concentrations were low (<1 mM) and decreased in
      the cauda whereas sorbitol concentration (4-7 mM) was rather uniform along the
      duct. AR was luminally located on microvilli in the caput and corpus with less
      presence distally and was present in the lumen. SDH was present apically and
      basally in epithelial cells throughout the epididymis and in the lumen. The
      observations are consistent with diffusion of circulating glucose into the lumen,
      its conversion via AR to sorbitol which accumulates in the lumen and the action
      of SDH on sorbitol to produce fructose. Sperm metabolism of glucose and fructose
      may explain their lower concentrations in the cauda and sorbitol could be a
      metabolic substrate or osmolyte required for volume regulation.

PMID- 16596634
TI  - Expression of a carboxy terminally truncated Stat5 with no transactivation domain
      in the mammary glands of transgenic mice inhibits cell proliferation during
      pregnancy, delays onset of milk secretion, and induces apoptosis upon involution.
AB  - Signal transducer and activator of transcription (Stat5) is a transcription
      factor, which transduces extracellular cytokine and growth-factor signals to the
      nuclei of mammalian cells. As a major mediator of prolactin action, it is
      involved in the regulation of the development, function, and survival of mammary
      epithelial cells. The carboxyl terminal of Stat5 encodes a transactivation domain
      (TAD), which interacts with coactivators and is crucial for the transcriptional
      induction of Stat5 target genes. To study the role of the Stat5 TAD in mediating
      Stat5 functions, a carboxy terminally truncated Stat5 variant (Stat5Delta750) was
      directed for expression in the mammary glands of transgenic mice by regulatory
      sequences of the beta-lactoglobulin (BLG) gene. Expression of Stat5Delta750 in
      mammary tissue reduced the rates of cell proliferation at mid and late pregnancy.
      Subsequently, morphological signs of milk secretion upon parturition were
      delayed. In double-transgenic mice, expression of Stat5Delta750 drastically
      decreased BLG/luciferase activity during lactation, but did not affect the
      expression and secretion of the endogenous beta-casein or alpha-lactalbumin into
      the milk. Expression of Stat5Delta750 also caused an increase in the number of
      apoptotic cells during mammary involution by a factor of 3 relative to control
      glands. Our data established a role for the Stat5 TAD in mediating the effects of
      Stat5 on mammary development, regulation of milk protein gene activity, and cell
      survival. The full effects of Stat5Delta750 may be partially buffered by the
      expression of endogenous wild-type Stat5 and the formation of truncated and wild
      type heterodimers.

PMID- 16596636
TI  - Electron paramagnetic resonance imaging of tumor hypoxia: enhanced spatial and
      temporal resolution for in vivo pO2 determination.
AB  - The time-domain (TD) mode of electron paramagnetic resonance (EPR) data
      collection offers a means of estimating the concentration of a paramagnetic probe
      and the oxygen-dependent linewidth (LW) to generate pO2 maps with minimal errors.
      A methodology for noninvasive pO2 imaging based on the application of TD-EPR
      using oxygen-induced LW broadening of a triarylmethyl (TAM)-based radical is
      presented. The decay of pixel intensities in an image is used to estimate T2*,
      which is inversely proportional to pO2. Factors affecting T2* in each pixel are
      critically analyzed to extract the contribution of dissolved oxygen to EPR line
      broadening. Suitable experimental and image-processing parameters were obtained
      to produce pO2 maps with minimal artifacts. Image artifacts were also minimized
      with the use of a novel data collection strategy using multiple gradients.
      Results from a phantom and in vivo imaging of tumor-bearing mice validated this
      novel method of noninvasive oximetry. The current imaging protocols achieve a
      spatial resolution of approximately 1.0 mm and a temporal resolution of
      approximately 9 s for 2D pO2 mapping, with a reliable oxygen resolution of
      approximately 1 mmHg (0.12% oxygen in gas phase). This work demonstrates that in
      vivo oximetry can be performed with good sensitivity, accuracy, and high spatial
      and temporal resolution.

PMID- 16596635
TI  - 32-element receiver-coil array for cardiac imaging.
AB  - A lightweight 32-element MRI receiver-coil array was designed and built for
      cardiac imaging. It comprises an anterior array of 21 copper rings (75 mm
      diameter) and a posterior array of 11 rings (107 mm diameter) that are arranged
      in hexagonal lattices so as to decouple nearest neighbors, and curved around the
      left side of the torso. Imaging experiments on phantoms and human volunteers show
      that it yields superior performance relative to an eight-element cardiac array as
      well as a 32-element whole-torso array for both traditional nonaccelerated
      cardiac imaging and 3D parallel imaging with acceleration factors as high as 16.

PMID- 16596637
TI  - A novel maternally transcribed homeobox gene, Eso-1, is preferentially expressed
      in oocytes and regulated by cytoplasmic polyadenylation.
AB  - The homeobox gene families play important roles in the transcriptional regulation
      of gene expression prior to and during embryo development. To identify novel
      homeobox genes expressed in early embryonic development, we conducted a
      degenerated oligonucleotide polymerase chain reaction (PCR) to screen a mouse
      embryonic stem (ES) cell cDNA library. A novel homeobox-containing gene, Eso-1,
      which is preferentially expressed in ES cells and ovaries, was identified. The
      full-length Eso-1 cDNA was found to be 1,710 bp with a predicted homeodomain that
      has no significant homology to previously reported homeodomain proteins. Eso-1
      was mapped to chromosome 14A3. Reverse transcription-polymerase chain reaction
      (RT-PCR) analyses showed that Eso-1 was expressed through oogenesis and
      continuing to be expressed through to the blastocyst stage. De novo expression of
      Eso-1 started at 13.5 days postcoitum in the ovaries, which coincides with the
      initiation of oogenesis. Northern blot analyses demonstrated that Eso-1 is
      preferentially expressed in both ovaries and ES cells as a 1.7-kb transcript.
      Results from whole mount in situ hybridization revealed that Eso-1 in oocytes
      showed increased expression from primordial to antral follicles. The 3'
      untranslated region of Eso-1 transcripts contained cytoplasmic polyadenylation
      sequences while the length of poly (A) tails changed during oocyte maturation,
      indicating that Eso-1 expression is controlled by time-dependent translational
      activation. We suggest that the novel homeodomain protein, Eso-1, plays a role
      during oocyte maturation and early embryonic development.

PMID- 16596638
TI  - hCG-dependent regulation of angiogenic factors in human granulosa lutein cells.
AB  - As prerequisite for development and maintenance of many diseases angiogenesis is
      of particular interest in medicine. Pathologic angiogenesis takes place in
      chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated
      with diabetes, and particularly in cancers. However, angiogenesis as a
      physiological process regularly occurs in the ovary. After ovulation the corpus
      luteum is formed by rapid vascularization of initially avascular granulosa lutein
      cell tissue. This process is regulated by gonadotropic hormones. In order to gain
      further insights in the regulatory mechanisms of angiogenesis in the ovary, we
      investigated these mechanisms in cell culture of human granulosa lutein cells. In
      particular, we determined the expression and production of several angiogenic
      factors including tissue inhibitor of matrix metalloproteinases-1 (TIMP-1),
      Leptin, connective tissue growth factor (CTGF), meningioma-associated
      complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In
      addition, we showed that human chorionic gonadotropin (hCG) has distinct effects
      on their expression and production. hCG enhances the expression and production of
      TIMP-1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it
      decreases the expression of Leptin. Our results provide evidence that hCG
      determines growth and development of the corpus luteum by mediating angiogenic
      pathways in human granulosa lutein cells. Hence we describe a further approach to
      understand the regulation of angiogenesis in the ovary.

PMID- 16596640
TI  - Investigation of in vivo 6DOF total knee arthoplasty kinematics using a dual
      orthogonal fluoroscopic system.
AB  - Fluoroscopic techniques have been recently used to detect in vivo knee joint
      kinematics. This article presents a technique that uses two fluoroscopes to form
      a dual orthogonal fluoroscopic system for accurately measuring in vivo 6DOF total
      knee arthoplasty (TKA) kinematics. The system was rigorously validated and used
      to investigate in vivo kinematics of 12 patients after cruciate-retaining TKA. In
      a repeatability study, the pose of two different TKA components was reproduced
      with standard deviations (SD) of 0.17 mm and 0.57 degrees about all three axes.
      In an accuracy study, the reproduced component positions were compared to the
      known component positions. Position and rotation mean errors were all within 0.11
      mm and 0.24 degrees, with SD within 0.11 mm and 0.48 degrees, respectively. The
      results of this study show that the matching process of the imaging system is
      able to accurately reproduce the spatial positions and orientations of both the
      femoral and tibial components. For CR TKA patients, a consistent anterior femoral
      translation was observed with flexion through 45 degrees of flexion, and
      thereafter, the femur translated posteriorly with further flexion. The medial
      lateral translation was measured to be less than 2 mm throughout the entire
      flexion range. Internal tibial rotation steadily increased through maximum
      flexion by approximately 6 degrees. Varus rotation was also measured with flexion
      but had a mean magnitude less than 2.0 degrees. In conclusion, the dual
      orthogonal fluoroscopic system accurately detects TKA kinematics and is
      applicable towards other joints of the musculoskeletal system, including the
      wrist, elbow, shoulder, ankle, and spine.

PMID- 16596639
TI  - Crystal structures of the complexes of a group IIA phospholipase A2 with two
      natural anti-inflammatory agents, anisic acid, and atropine reveal a similar mode
      of binding.
AB  - Secretory low molecular weight phospholipase A(2)s (PLA(2)s) are believed to be
      involved in the release of arachidonic acid, a precursor for the biosynthesis of
      pro-inflammatory eicosanoids. Therefore, the specific inhibitors of these enzymes
      may act as potent anti-inflammatory agents. Similarly, the compounds with known
      anti-inflammatory properties should act as specific inhibitors. Two plant
      compounds, (a) anisic acid (4-methoxy benzoic acid) and (b) atropine (8-methyl-8
      azabicyclo oct-3-hydroxy-2-phenylpropanoate), have been used in various
      inflammatory disorders. Both compounds (a) and (b) have been found to inhibit
      PLA(2) activity having binding constants of 4.5 x 10(-5) M and 2.1 x 10(-8) M,
      respectively. A group IIA PLA(2) was isolated and purified from the venom of
      Daboia russelli pulchella (DRP) and its complexes were made with anisic acid and
      atropine. The crystal structures of the two complexes (i) and (ii) of PLA(2) with
      compounds (a) and (b) have been determined at 1.3 and 1.2 A resolutions,
      respectively. The high-quality observed electron densities for the two compounds
      allowed the accurate determinations of their atomic positions. The structures
      revealed that these compounds bound to the enzyme at the substrate - binding
      cleft and their positions were stabilized by networks of hydrogen bonds and
      hydrophobic interactions. The most characteristic interactions involving Asp 49
      and His 48 were clearly observed in both complexes, although the residues that
      formed hydrophobic interactions with these compounds were not identical because
      their positions did not exactly superimpose in the large substrate-binding
      hydrophobic channel. Owing to a relatively small size, the structure of anisic
      acid did not alter upon binding to PLA(2), while that of atropine changed
      significantly when compared with its native crystal structure. The conformation
      of the protein also did not show notable changes upon the bindings of these
      ligands. The mode of binding of anisic acid to the present group II PLA(2) is
      almost identical to its binding with bovine pancreatic PLA(2) of group I. On the
      other hand, the binding of atropine to PLA(2) is similar to that of another plant
      alkaloid aristolochic acid.

PMID- 16596641
TI  - Unfolding transition state and intermediates of the tumor suppressor p16INK4a
      investigated by molecular dynamics simulations.
AB  - The ankyrin repeat is one of the most common protein motifs and is involved in
      protein-protein interactions. It consists of 33 residues that assume a beta
      hairpin helix-loop-helix fold. Mutagenesis and kinetic experiments (Phi-value
      analysis of the folding transition state) have shown that the tumor suppressor
      p16(INK4a), a four-repeat protein, unfolds sequentially starting from the two N
      terminal repeats. Here, the flexibility of p16(INK4a) at room temperature and its
      unfolding mechanism at high temperature have been investigated by multiple
      molecular dynamics runs in explicit water for a total simulation time of 0.65
      micros. The transition state ensemble (TSE) of p16(INK4a) was identified by
      monitoring both the deviation from the experimental Phi values and sudden
      conformational changes along the unfolding trajectories. Conformations in the TSE
      have a mainly unstructured second repeat whereas the other repeats are almost
      completely folded. A rigid-body displacement of the first repeat involving both a
      rotation and translation is observed in all molecular dynamics simulations at
      high temperature. The Trp(15), Pro(75), and Ala(76) side-chains are more buried
      in the TSE than the native state. The sequential unfolding starting at the second
      repeat is in agreement with the mutagenesis studies whereas the displacement of
      the first repeat and the presence of nonnative interactions at the TSE are
      simulation results which supplement the experimental data. Furthermore, the
      unfolding trajectories reveal the presence of two on-pathway intermediates with
      partial alpha-helical structure. Finally, on the basis of the available
      experimental and simulation results we suggest that in modular proteins the shift
      of the folding TSE toward the native structure upon reduction of the number of
      tandem repeats is consistent with the Hammond effect.

PMID- 16596643
TI  - UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 6
      (ppGalNAc-T6) mRNA as a potential new marker for detection of bone marrow
      disseminated breast cancer cells.
AB  - The evaluation of disseminated epithelial tumor cells in patients with early
      stages of breast cancer has generated considerable interest because of its
      potential association with poor clinical outcome. Considering that O
      glycosylation pathways are frequently altered in breast cancer, we performed this
      work to evaluate the potential usefulness of UDP-N-acetyl-D
      galactosamine:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts) (a
      family of glycosyltransferases which catalyze the first key step of mucin-type O
      glycosylation) to detect disseminated cells in bone marrow samples from patients
      with operable breast cancer. Using RT-PCR assays, we studied the gene expression
      of 9 enzymes (ppGalNAc-T1-T9). Among the ppGalNAc-Ts expressed by breast tumors (
      T1, -T2, -T3, -T6 and -T7), the best specificity (negative results on all PBMN
      cell samples from healthy donors) was shown for ppGalNAc-T6. Thus, we selected
      this enzyme as a target gene for further evaluation. ppGalNAc-T6 mRNA was found
      in 22/25 (88%) breast cancer samples, in all 3 human breast cancer cell lines
      evaluated (MCF-7, ZR75-1 and T47D), in 1/30 (3%) PBMN cells and 0/19 bone marrow
      samples obtained from patients without cancer. Using this method, 22/61 (36%)
      patients with breast cancer, who underwent curative surgery, showed positive
      ppGalNAc-T6 mRNA in bone marrow aspirates obtained prior to surgery, including
      11/34 patients with stage-I or -II, without histopathological lymph node
      involvement. In a preliminary follow-up evaluation, 19/61 patients experienced
      recurrence of the disease. ppGalNAc-T6 was positive in 11/19 (57.9%) of these
      patients. Interestingly, in the group of patients without lymph node involvement,
      disease recurrence was observed in 54.5% of patients who showed ppGalNAc-T6 mRNA
      positive bone marrow aspirates and only in 4.3% of patients when ppGalNAc-T6 was
      negative (p = 0.014). These results indicate that ppGalNAc-T6 mRNA could be a
      specific marker applicable to the molecular diagnosis of breast cancer cells
      dissemination.

PMID- 16596642
TI  - A microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated
      with risk for melanoma.
AB  - Heme oxygenase-1 (HO-1) has been demonstrated to play an important role in the
      regulation of signaling systems, which are involved in the control of cell cycle
      progression and apoptosis. Recently, a (GT)n dinucleotide repeat polymorphism in
      the HO-1 promoter was shown to modulate HO-1 gene expression. Short (<25 GT)
      repeats are associated with an increased HO-1 upregulation after stimulation than
      are longer repeats. Malignant melanoma (MM) is the most serious cutaneous
      malignancy with high tendency to aggressive growth and resistance to apoptosis.
      Therefore, we sought to study the influence of this polymorphism on the
      progression of MM. We determined the HO-1 promoter genotype in 152 patients with
      MM and 398 healthy controls and studied their association in regard to
      susceptibility to MM, Breslow thickness and disease-free survival. In our study,
      the homozygous short allele with <25 (GT)n repeats (S/S) was found more
      frequently in the melanoma group compared to the healthy control population (21
      and 12%, respectively). The calculated risk for acquiring primary MM in S/S
      carriers was 2-fold higher compared to those with L-allele types (95% confidence
      interval: 1.2-2.4, p = 0.03). Additionally, the S/S genotype was significantly
      associated with primary tumors with deeper Breslow thickness compared to L-allele
      (>25 repeats) carriers (mean Breslow thickness: 4.0 +/- 2.9 mm versus 3.1 +/- 1.7
      mm, p = 0.03). These data suggest that HO-1 might render a higher risk for MM in
      S/S genotype individuals and could represent an important candidate gene in the
      pathogenesis and growth of malignant melanoma.

PMID- 16596644
TI  - Monitoring of WT1-specific cytotoxic T lymphocytes after allogeneic hematopoietic
      stem cell transplantation.
AB  - Donor-derived cytotoxic T lymphocytes (CTL) that respond to tumor antigens emerge
      after hematopoietic stem cell transplantation (HSCT), particularly in association
      with the status of immune recovery. To analyze the frequency of CTL against PR1,
      PRAME and WT1 after HSCT, a tetramer-based analysis was performed in 97 samples
      taken from 35 patients (9 AML, 11 MDS, 2 CML, 4 ALL, 7 lymphoma and 2 renal cell
      carcinoma [RCC]) with the HLA-A02 phenotype. Regarding PR1, only 1 sample showed
      the presence of tetramer-positive cells (0.04%/lymphocyte). Similarly, in PRAME,
      only 10 of 97 samples were sporadically positive with low titers. For WT1,
      positive results were detected in 39 of 97 samples and 7 (2 CML, 1 ALL, 2
      lymphoma and 2 RCC) patients clearly showed positive results more than once. On
      the basis of these results, we performed serial analyses of WT1-specific CTL
      during the clinical course in 2 patients with RCC, who underwent HSCT with a
      reduced-intensity regimen, to examine the precise correlation between the
      kinetics of CTL, the occurrence of GVHD and the observed clinical response. A
      higher positive rate for WT1-specific CTL and a correlation with the clinical
      response suggest that WT1 may be a useful antigen for a wider monitoring
      application.

PMID- 16596645
TI  - Trends in the incidence of cancer in Qidong, China, 1978-2002.
AB  - A population-based cancer registry was established in Qidong, Jiangsu Province,
      China, in 1972, and the trends in incidence rates of the major cancer sites have
      been analyzed for a 25-year period, 1978-2002. Five-year age-specific rates,
      crude incidence rates, world age-standardized rates (ASR), percent change (PC)
      and annual percent change (APC) were calculated using annual data on population
      size, and estimates of its age structure. The indices of histological
      verification of diagnosis, death certificate only and proportion of mortality to
      incidence were employed for assessing the registration quality. A total of 51,933
      incident cases of cancer were registered in Qidong from years 1978 to 2002, with
      a male-to-female sex ratio of 1.9:1. Crude incidence increased markedly over the
      25-year period (PC and APC of +55.6% and +2.1%, respectively), but ASR showed a
      slight decrease (-0.4% in males, and -0.3% in females), indicating that the major
      part of this is due to population ageing. The leading cancer sites in rank were
      liver (average ASR = 50.8 per 100,000), stomach (26.7), lung (22.7), colon-rectum
      (8.9), oesophagus (7.4) and breast (5.4). Cancers of liver, lung, colon-rectum
      and female breast all showed increases in incidence during the study period, with
      APCs (ASR) of +0.1%, +1.7% and +1.4% for males, and +0.2%, +0.9%, +1.9% and +1.1%
      for females, while the cancers of stomach (APC: -3.2% in male, and --2.4% in
      female) and cervix (APC: -4.7%) showed notable declines. Examination of age
      specific rates showed declining trends in the younger generations for liver
      cancer, but increases for cervix cancer. The results underline the increasing
      importance of cancer as a cause of mortality and morbidity in a population that
      is ageing and undergoing profound changes in socioeconomic development and
      lifestyle. The cancers of high lethality that have been common in the Chinese
      population (liver, stomach, oesophagus) are showing some evidence of decline, at
      least in younger generations, but they remain major problems. At the same time,
      the cancers associated with economically "developed" societies -- lung, colon
      rectum and female breast -- are showing increases. The population-based cancer
      registry is an indispensable tool for providing data for planning and evaluation
      of programmes for cancer control in all societies.

PMID- 16596646
TI  - Structure of phage protein BC1872 from Bacillus cereus, a singleton with new
      fold.

PMID- 16596647
TI  - Socioeconomic gradients in clinical stage at presentation and survival among
      breast cancer patients in the Stockholm area 1977-1997.
AB  - A program to ensure an equivalent standard of care for all patients with breast
      cancer was initiated in the Stockholm area in the mid 1970s. As part of an
      evaluation of this program, social gradients in clinical stage at presentation
      and survival were analyzed among patients diagnosed during 1977 through 1997. The
      patients (n = 15,021) were selected from a database covering about 88% of all
      diagnosed breast cancer cases in the region. Putative associations were analyzed
      between clinical stage, survival and different socioeconomic indicators (level of
      education, income and occupation). There were significant social differences (p <
      0.01) in distribution of clinical stage as well as in total and stage-specific
      survival. High income, more skilled work and a high level of education were all
      associated with clinically less advanced tumors and hence better survival.
      However, stage-specific survival differences were mostly generated by differences
      in nonbreast cancer mortality. The results indicate social inequalities regarding
      awareness of the disease and/or access to early detection. Social gradients in
      nonbreast cancer mortality were also found to influence observed survival. In
      contrast, we observed no significant social differences in stage-specific breast
      cancer mortality.

PMID- 16596648
TI  - Smoking and mortality from esophageal cancer in China: a large case-control study
      of 19,734 male esophageal cancer deaths and 104,846 living spouse controls.
AB  - An innovative population-based case-control study was conducted in a national
      mortality survey to assess the hazards of tobacco use on esophageal cancer among
      Chinese men. Cases were 19,734 males aged 35 years or older, who died of
      esophageal cancer during 1986-1988. Controls were 104,846 male living spouses of
      the same age when their wife died (of any cause) during the same period in the
      same county or city. The absolute esophageal cancer death rates were higher in
      smokers than those in nonsmokers in all geographical groups. The relative risks
      for esophageal cancer were 1.88 (95% CI: 1.73-2.05) and 1.39 (95% CI: 1.28-1.50)
      in urban and rural men, respectively, after adjustment for other relevant
      covariates including age group (5 years) and locality. When the calculation was
      restricted to men aged 35-69, the risk ratios for current cigarette smokers
      increased significantly with increasing number of cigarettes smoked daily and
      duration of smoking. Tobacco use, in any form, is an important risk factor for
      esophageal cancer in Chinese men. Selecting living spouses as controls is a
      unique and useful approach in the design of case-control studies of cigarette
      smoking.

PMID- 16596649
TI  - A combinatorial score to distinguish biological and nonbiological protein-protein
      interfaces.
AB  - With the large amount of protein-protein complex structural data available, to
      understand the key features governing the specificity of protein-protein
      recognition and to define a suitable scoring function for protein-protein
      interaction predictions, we have analyzed the protein interfaces from geometric
      and energetic points of view. Atom-based potential of mean force (PMFScore),
      packing density, contact size, and geometric complementarity are calculated for
      crystal contacts in 74 homodimers and 91 monomers, which include real biological
      interactions in dimers and nonbiological contacts in monomers and dimers. Simple
      cutoffs were developed for single and combinatorial parameters to distinguish
      biological and nonbiological contacts. The results show that PMFScore is a better
      discriminator between biological and nonbiological interfaces comparable in size.
      The combination of PMFScore and contact size is the most powerful pairwise
      discriminator. A combinatorial score (CFPScore) based on the four parameters was
      developed, which gives the success rate of the homodimer discrimination of 96.6%
      and error rate of the monomer discrimination of 6.0% and 19.8% according to
      Valdar's and our definition, respectively. Compared with other statistical
      learning models, the cutoffs for the four parameters and their combinations are
      directly based on physical models, simple, and can be easily applied to protein
      protein interface analysis and docking studies.

PMID- 16596650
TI  - Distribution of co-activators CBP and p300 during mouse oocyte and embryo
      development.
AB  - cAMP response element binding protein (CREB)-binding protein (CBP) and p300 are
      two structurally related transcriptional co-activators that activate expression
      of many eukaryotic genes. Current dogma would suggest that these transcriptional
      co-activators have similar mechanisms of transcription regulation. Studies of CBP
      or p300 homozygotic mouse mutants indicate that normal embryogenesis requires the
      existence of both factors. However, whether this is indicative of a dosage effect
      of these two proteins, or whether these proteins play different roles in mouse
      embryo development is not clear. Here we demonstrated that both factors are first
      found in the cytoplasm of oocytes within primordial follicles, and that they
      enter into the oocyte nucleus at different stages of oocyte growth, suggesting
      that they may play different roles in gene expression during oocyte growth and
      development. Consistent with this model, in the pre-implantation mouse embryos,
      from the two-cell stage to the blastocyst stage, the localizations of CBP and
      p300 are different, at times opposite, indicating that CBP and p300 also have
      different functions in early mouse embryogenesis.

PMID- 16596651
TI  - Joint capsule matrix turnover in a rabbit model of chronic joint contractures:
      Correlation with human contractures.
AB  - To evaluate changes in matrix molecules of the joint capsule, the right knees of
      24 skeletally mature female NZW rabbits were immobilized while the contralateral
      limb served as an unoperated control. The immobilization was discontinued at 8
      weeks and the rabbits were divided among four groups (n = 6) based on the number
      of weeks the right knees were remobilized: 0, 8, 16, or 32. Three rabbits (six
      knees) that did not have operations provided normal control joint capsules. The
      mRNA levels for collagen types I, II, and III, and MMP-1 and -13 were
      significantly increased in the joint capsules of the contracture knees in all
      groups when compared to normal and contralateral limb joint capsules. In
      contrast, the mRNA levels for TIMP-1, -2, and -3 were decreased in the joint
      capsules of the contracture knees in all groups when compared to normal and
      contralateral limb joint capsules. The mRNA levels for lumican and decorin were
      increased in the joint capsules of the contracture knees in all groups when
      compared to normal capsules. Many of the changes observed in this animal model
      are similar to those observed in human joint capsules from posttraumatic elbow
      contractures, supporting the value of this rabbit model.

PMID- 16596652
TI  - Relevance of osteoinductive biomaterials in critical-sized orthotopic defect.
AB  - Several publications have shown the phenomenon of osteoinduction by biomaterials
      to be real. However, whether the ability of a biomaterial to initiate bone
      formation in ectopic implantation sites improves the performance of such
      osteoinductive biomaterial in clinically relevant orthotopic sites remains
      unclear. No studies have been published in which osteoinductive potential of a
      biomaterial is directly related to its performance orthotopically. In this study,
      we compared osteoinductive and nonosteoinductive biphasic calcium-phosphate (BCP)
      ceramics ectopically and in a clinically relevant critical-sized orthotopic
      defect in goats. The two materials, BCP1150 and BCP1300, had similar chemical
      compositions, crystallinities, and macrostructures, but their microstructures
      differed significantly. BCP1150, sintered at a lower temperature, had a large
      amount of micropores, small average crystal size, and hence a high specific
      surface area. In contrast, BCP1300, with few micropores, had a significantly
      lower specific surface area as compared to BCP1150. Twelve-week intramuscular
      implantation in goats (n = 10) showed that bone was induced in all BCP1150
      implants, while no signs of bone formation were found in any of the BCP1300
      implants. After 12 weeks of implantation in a bilateral critical-sized iliac wing
      defect in the same goats, BCP1150 showed significantly more bone than BCP1300. In
      addition, the analysis of fluorochrome markers, which were administered to the
      animals 4, 6, and 8 weeks after implantation to follow the bone growth dynamics,
      showed an earlier start of bone formation in BCP1150 as compared to BCP1300.
      Significantly better performance of an osteoinductive ceramic in a critical-sized
      orthotopic defect in a large animal model in comparison to a nonosteoinductive
      ceramic suggests osteoinduction to be clinically relevant. Further improvement of
      material osteoinductive properties is thus a significant step forward in the
      search for alternatives for autologous bone graft.

PMID- 16596653
TI  - Anthropometry and the risk of epithelial ovarian cancer.
AB  - BACKGROUND: The association between anthropometric factors and ovarian cancer
      risk was investigated using data from 762 cases and 1348 controls participating
      in a population-based case-control study in the Delaware Valley from 1994-1998.
      Because factors such as oral contraceptive (OC), hormone therapy (HT), and parity
      may affect weight and hormone levels, the associations were examined in women
      with and without these characteristics. METHODS: Unconditional logistic
      regression was used to calculate odds ratios and 95% confidence intervals while
      controlling for age, race, parity, family history of ovarian cancer, tubal
      ligation, and OC use. RESULTS: Compared with controls, cases were taller and
      heavier in recent years and at age 18. Results did not differ by OC or HT use.
      However, anthropometric associations differed significantly based on parity, as
      increasing anthropometric measures were associated with increased ovarian cancer
      risk among nulliparous women only. Adjusted OR for recent body mass index (BMI)
      quartile 4 compared with quartile 1 for nulliparous women was 2.53 (95%
      confidence interval [CI]: 1.39, 4.61) compared with 0.96 (95% CI: 0.70, 1.31) for
      parous women. Additionally, adult weight gain was significant only for
      nulliparous women. Adjusted OR for weight change (recent to age 18) quartile 4
      compared with quartile 1 for nulliparous women was 3.73 (95% CI: 1.88, 7.42)
      versus 1.09 (95% CI: 0.78, 1.51) for parous women. CONCLUSIONS: BMI and weight in
      women's adult lifetime may be positively associated with ovarian cancer risk.
      Observations were most apparent for nulliparous women, possibly reflecting an
      interaction between local inflammation caused by incessant ovulation and
      increased estrogen exposure on ovarian epithelium.

PMID- 16596654
TI  - Analysis of functional image analysis contest (FIAC) data with brainvoyager QX:
      From single-subject to cortically aligned group general linear model analysis and
      self-organizing group independent component analysis.
AB  - The Functional Image Analysis Contest (FIAC) 2005 dataset was analyzed using
      BrainVoyager QX. First, we performed a standard analysis of the functional and
      anatomical data that includes preprocessing, spatial normalization into Talairach
      space, hypothesis-driven statistics (one- and two-factorial, single-subject and
      group-level random effects, General Linear Model [GLM]) of the block- and event
      related paradigms. Strong sentence and weak speaker group-level effects were
      detected in temporal and frontal regions. Following this standard analysis, we
      performed single-subject and group-level (Talairach-based) Independent Component
      Analysis (ICA) that highlights the presence of functionally connected clusters in
      temporal and frontal regions for sentence processing, besides revealing other
      networks related to auditory stimulation or to the default state of the brain.
      Finally, we applied a high-resolution cortical alignment method to improve the
      spatial correspondence across brains and re-run the random effects group GLM as
      well as the group-level ICA in this space. Using spatially and temporally
      unsmoothed data, this cortex-based analysis revealed comparable results but with
      a set of spatially more confined group clusters and more differential group
      region of interest time courses.

PMID- 16596655
TI  - Impact of estrogen receptor expression and other clinicopathologic features on
      tamoxifen use in ductal carcinoma in situ.
AB  - BACKGROUND: Recent data have demonstrated that benefit from adjuvant tamoxifen
      therapy for patients with ductal carcinoma in situ (DCIS) is limited to estrogen
      receptor (ER)-positive lesions. The objective of the current study was to
      correlate clinicopathologic features of DCIS with ER expression and the impact of
      this information on tamoxifen counseling. METHODS: Women with DCIS who were
      treated from 2001 to 2004 were evaluated. Routine ER staining was initiated in
      January 2003. RESULTS: Ninety-four women (mean age, 57.6 years) were analyzed.
      The mean DCIS size was 0.98 cm. ER-staining was performed in 55 lesions, and 76%
      were ER-positive. All Grade 1 and 2 DCIS lesions were ER-positive, compared with
      54% of high-grade lesions (P<.001); no other clinicopathologic feature
      significantly predicted ER status. Overall, 58 patients (62%) were offered
      tamoxifen, and the rates were similar for the pre-ER and post-ER staining
      periods. In the pre-ER staining period, surgical treatment and grade were
      associated with offering tamoxifen (75% of patients who underwent breast
      conservation vs. 40% of patients who underwent mastectomy; P = .03; 78% of
      patients with Grade 1 or 2 lesions vs. 45% of patients with Grade 3 lesions; P =
      .04). In the post-ER staining period, however, only ER status was correlated
      significantly with offering tamoxifen (71% of patients with ER-positive lesions
      vs. 31% of patients with ER-negative lesions; P = .01). Approximately 66% of
      patients who were offered tamoxifen agreed to treatment (approximately 33% of the
      total DCIS study sample). No clinicopathologic features predicted for tamoxifen
      acceptance by patients in either the pre-ER or post-ER staining periods.
      CONCLUSIONS: Seventy-five percent of DCIS lesions were ER-positive. ER staining
      significantly influenced the likelihood that clinicians would offer tamoxifen to
      patients with DCIS, but it had no impact on whether patients accepted treatment.

PMID- 16596656
TI  - The "y" symbol: an important classification tool for neoadjuvant cancer
      treatment.

PMID- 16596657
TI  - Endoscopic optical coherence tomography and laser-induced fluorescence
      spectroscopy in a murine colon cancer model.
AB  - BACKGROUND AND OBJECTIVES: The diagnostic feasibility of optical coherence
      tomography (OCT) and laser-induced fluorescence (LIF) have been evaluated for
      human colorectal cancer. This study applies these technologies to a murine model
      of colorectal adenoma. STUDY DESIGN/MATERIALS AND METHODS: The lower colon of 10
      Apc(Min) and two C57BL/6J mice was surveyed over five 4-week intervals using a
      prototype 2.0 mm diameter OCT-LIF endoscope-based system. Four categories were
      histologically classified: control C57BL/6J, adenomatous, non-diseased regions of
      adenomatous, and non-diseased Apc(Min). OCT images were compared to histology.
      Spectra from the four categories were compared via the Student's t-test. RESULTS:
      Three Apc(Min) and two control mice completed the study. One adenoma was
      histologically identified; OCT visualized mucosal thickening/abnormal mass
      development over the imaging timepoints. LIF spectral comparisons revealed
      decreased 405 nm intensity and the presence of a peak at 680 nm in the
      adenomatous Apc(Min). CONCLUSIONS: These preliminary data indicate endoscopic OCT
      LIF has the potential to identify colorectal adenomas in murine models.

PMID- 16596658
TI  - Measurement of protection afforded by ultraviolet-absorbing window film using an
      in vitro model of photodamage.
AB  - BACKGROUND AND OBJECTIVES: The effects of chronic sun damage including
      telangiectasias, solar lentigos, rhytides, enlarged pores, sagging skin, and pre
      cancerous and cancerous growths are among the most common presenting complaints
      in a dermatologist's office. These changes are often worse on the driver's side
      of the face, emphasizing the role of UVA exposure received while driving in
      producing these changes. This study was undertaken to measure the ability of car
      window glass alone and in combination with ultraviolet (UV)-absorbing film to
      reduce UV-damage as measured using an established in vitro model of
      photoprotection. STUDY DESIGN MATERIALS AND METHODS: Using the 3T3 neutral red
      uptake photoprotection assay with solar simulating radiation (SSR) administered
      by a xenon arc solar simulator, we measured the photoprotection ability of auto
      glass, window film that filters UV radiation, and the combination of window film
      and auto glass. RESULTS: As measured by the 3T3 neutral red uptake
      photoprotection assay, auto glass reduced cell death from SSR by 29%, while
      window film reduced it 90%, and the combination of auto glass and film reduced
      cell death by 93%, when compared to unfiltered SSR. CONCLUSIONS: Window film that
      filters UV radiation results in dramatic reductions in cytotoxicity when measured
      by the neutral red uptake photoprotection assay. Widespread use of window film
      provides an ever-present barrier to ultraviolet A (UVA) exposure and could
      potentially reduce the detrimental effects of UVA, including photoaging, skin
      cancer, and ocular damage, such as cataracts. In addition, such film is essential
      for patients suffering from conditions sensitive to UV radiation, such as lupus
      erythematosis.

PMID- 16596659
TI  - Laser versus intense pulsed light: Competing technologies in dermatology.
AB  - Lasers have been competing with non-laser intense pulsed light (IPL) sources in
      the cosmetic arena over the past 10 years. Initially IPLs were somewhat
      cumbersome and accepted by a minority of "serious" practitioners. Recently,
      however, the popularity of full-face visible light skin rejuvenation, enhanced
      engineering of IPLs, and favorable cost versus many lasers, have lead to a
      proliferation of IPL devices. No longer a stepchild in the rejuvenation market,
      IPLs may overtake lasers as the devices of choice among most physicians. We
      review the pros and cons of lasers and IPLs within the context of design, cost,
      and other practical concerns for a typical office-based practice.

PMID- 16596660
TI  - Comparing and combining light dose fractionation and iron chelation to enhance
      experimental photodynamic therapy with aminolevulinic acid.
AB  - BACKGROUND AND OBJECTIVES: Enhancement of photodynamic therapy (PDT) with 5
      aminolevulinic acid (ALA) has been demonstrated experimentally using light dose
      fractionation or CP94 iron chelation. This study extends this research. STUDY
      DESIGN/MATERIALS AND METHODS: In normal rat colon, CP94 administration and light
      dose fractionation were independently and concurrently employed to enhance ALA
      PDT. In colonic rat tumors, the most successful enhancement regimes were employed
      separately. RESULTS: Independent use of light dose fractionation and iron
      chelation produced similar results in normal colon (2.4- and 2.9-fold more
      necrosis than controls, respectively). Using both techniques simultaneously
      produced fivefold enhancement. In the colonic tumors, light dose fractionation
      and iron chelation (using different parameters) produced two and five times the
      volume of necrosis, respectively. CONCLUSIONS: Both techniques significantly
      enhanced ALA-PDT in the normal and neoplastic tissues investigated and produced
      similar levels of enhancement when comparable parameters were employed.
      Concurrent use of light dose fractionation and iron chelation in normal colon
      produced considerably more enhancement than either technique could achieve
      independently.

PMID- 16596662
TI  - A newly established mutant strain with mild-type ocular coloboma (retinochoroidal
      coloboma without microphthalmia) in albino mice.
AB  - BACKGROUND: A complicated malformation of the fundus accompanied by typical
      ocular coloboma was detected in albino fatty liver Shionogi (FLS) mice. We
      elucidated a new type of 3-dimensional anomalous structure inside the eye in this
      mouse strain. METHODS: The fundi of FLS mice aged 1, 3, 5, and 20 weeks were
      observed intensively, both macroscopically and by light microscopy. For the
      prenatal study, coronal serial sections of eyes of FLS embryos were examined by
      light microscopy on gestation day (GD) 15.0. RESULTS: The frequency of ocular
      coloboma was almost 70% in FLS mice, and the inheritance mode of this anomaly is
      suggested to be autosomal recessive with incomplete penetrance. Stereoscopic
      observation and light microscopy revealed that the mice had characteristic fundus
      features at any age during the postnatal period. Following ectopic ciliary
      epithelia, the surface of the retina protruded like a roof, and on the opposite
      side of the "roof," a translucent membrane without retinal tissue and choroidal
      tissue was also consistently detected in the inferior part of the fundus. On GD
      15.0, the inner layer and the outer layer were not normally fused at the optic
      fissure, where a part of the outer layer was absent and the irregular fold of the
      inner layer was conspicuous in the colobomatous eye of the FLS embryo.
      CONCLUSIONS: The characteristics of the ocular coloboma in FLS mice are thought
      to be similar to a mild-type malformation in humans. These ocular defects seem to
      be situated along the failed fetal optic fissure.

PMID- 16596663
TI  - Production of target-specific recombinant human polyclonal antibodies in
      mammalian cells.
AB  - We describe the expression and consistent production of a first target-specific
      recombinant human polyclonal antibody. An anti-Rhesus D recombinant polyclonal
      antibody, Sym001, comprised of 25 unique human IgG1 antibodies, was produced by
      the novel Sympress expression technology. This strategy is based on site-specific
      integration of antibody genes in CHO cells, using the FRT/Flp-In recombinase
      system. This allows integration of the expression construct at the same genomic
      site in the host cells, thereby reducing genomic position effects. Different
      bioreactor batches of Sym001 displayed highly consistent manufacturing yield,
      antibody composition, binding potency, and functional activity. The results
      demonstrate that diverse recombinant human polyclonal antibody compositions can
      be reproducibly generated under conditions directly applicable to industrial
      manufacturing settings and present a first recombinant polyclonal antibody which
      could be used for treatment of hemolytic disease of the newborn and/or idiopathic
      thrombocytopenic purpura.

PMID- 16596664
TI  - NO removal in continuous BioDeNOx reactors: Fe(II)EDTA2- regeneration, biomass
      growth, and EDTA degradation.
AB  - BioDeNOx is a novel technique for NOx removal from industrial flue gases. In
      principle, BioDeNOx is based on NO absorption into an aqueous Fe(II)EDTA2-
      solution combined with biological regeneration of that scrubber liquor in a
      bioreactor. The technical and economical feasibility of the BioDeNOx concept is
      strongly determined by high rate biological regeneration of the aqueous
      Fe(II)EDTA2- scrubber liquor and by EDTA degradation. This investigation deals
      with the Fe(II)EDTA2- regeneration capacity and EDTA degradation in a lab-scale
      BioDeNOx reactor (10-20 mM Fe(II)EDTA2-, pH 7.2 +/- 0.2, 55 degrees C), treating
      an artificial flue gas (1.5 m3/h) containing 60-155 ppm NO and 3.5-3.9% O2. The
      results obtained show a contradiction between the optimal redox state of the
      aqueous FeEDTA solution for NO absorption and the biological regeneration. A low
      redox potential (below -150 mV vs. Ag/AgCl) is needed to obtain a maximal NO
      removal efficiency from the gas phase via Fe(II)EDTA2- absorption. Fe(III)EDTA-
      reduction was found to be too slow to keep all FeEDTA in the reduced state.
      Stimulation of Fe(III)EDTA- reduction via periodical sulfide additions (2 mM
      spikes twice a week for the conditions applied in this study) was found to be
      necessary to regenerate the Fe(II)EDTA2- scrubber liquor and to achieve stable
      operation at redox potentials below -150 mV (pH 7.2 +/- 0.2). However, redox
      potentials of below -200 mV should be avoided since sulfide accumulation is
      unwanted because it is toxic for NO reduction. Very low values for biomass growth
      rate and yield, respectively, 0.043/d and 0.009 mg protein per mg ethanol, were
      observed. This might be due to substrate limitations, that is the electron
      acceptors NO and presumably polysulfide, or to physiological stress conditions
      induced by the EDTA rich medium or by radicals formed in the scrubber upon the
      oxidation of Fe(II)EDTA2- by oxygen present in the flue gas. Radicals possibly
      also induce EDTA degradation, which occurs at a substantial rate: 2.1 (+/-0.1)
      mM/d under the conditions investigated.

PMID- 16596665
TI  - Interpretation of metabolic flux maps by limitation potentials and constrained
      limitation sensitivities.
AB  - Two new concepts, "Limitation Potential" and "Constraint Limitation Sensitivity"
      are introduced that use definitions derived from metabolic flux analysis (MFA)
      and metabolic network analysis (MNA). They are applied to interpret a measured
      flux distribution in the context of all possible flux distributions and thus
      combine MFA with MNA. The proposed measures are used to quantify and compare the
      influence of intracellular fluxes on the production yield. The methods are purely
      based on the stoichiometry of the network and constraints that are given from
      irreversible fluxes. In contrast to metabolic control analysis (MCA), within this
      approach no information about the kinetic mechanisms are needed. A limitation
      potential (LP) is defined as the reduction of the reachable (theoretical) maximum
      by a measured flux. Measured fluxes that strongly narrow the reachable maximum
      are assumed to be limiting as the network has no ability to counterbalance the
      restriction due to the observed flux. In a second step, the sensitivity of the
      reduced maximum is regarded. This measure provides information about the
      necessitated changes to reach higher yields. The methods are applied to interpret
      the capabilities of a network based on measured fluxes for a L-phenylalanine
      producer. The strain was examined by a series of experiments and three flux maps
      of the production phase are analyzed. It can be shown that the reachable yield is
      drastically reduced by the measured efflux into the TCA cycle, while the
      oxidative pentose-phosphate pathway only plays a secondary role on the reachable
      maximum.

PMID- 16596666
TI  - Altering lipase activity and enantioselectivity in organic media using organo
      soluble bases: Implication for rate-limiting proton transfer in acylation step.
AB  - With the hydrolytic resolution of (R,S)-naproxen 2,2,2-trifluoroethyl esters via
      a partially purified papaya lipase (PCPL) in water-saturated isooctane as the
      model system, the enzyme activity, and enantioselectivty is altered by adding a
      variety of organo-soluble bases that act as either enzyme activators (i.e., TEA,
      MP, TOA, DPA, PY, and DMA) or enzyme inhibitors (i.e., PDP, DMAP, and PP).
      Triethylamine (TEA) is selected as the best enzyme activator as 2.24-fold
      increase of the initial rate for the (S)-ester is obtained when adding 120 mM of
      the base. By using an expanded Michaelis-Menten mechanism for the acylation step,
      the kinetic analysis indicates that the proton transfer for the breakdown of
      tetrahedral intermediates to acyl-enzyme intermediates is the rate-limiting step,
      or more sensitive than that for the formation of tetrahedral intermediates when
      the enzyme activators of different pKa are added. However, no correlation for the
      proton transfers in the acylation step is found when adding the bases acting as
      enzyme deactivators.

PMID- 16596667
TI  - Selective separation of cationic peptides from a tryptic hydrolysate of beta
      lactoglobulin by electrofiltration.
AB  - Electrofiltration (EF) was used to selectively separate cationic (basic) peptides
      contained in a tryptic beta-lactoglobulin (beta-LG) hydrolysate, with particular
      emphasis on the isolation of basic sequence beta-LG 142-148, which is a potential
      antihypertensive peptide. Both the influence of feed solution pH and operating
      parameters (transmembrane pressure, feed velocity) were assessed to find optimum
      conditions enabling the fractionation between peptides during EF. The cathode (-)
      was inserted in the permeate side to increase the separation of basic peptides
      contained in the tryptic beta-LG hydrolysate as compared to conventional NF. The
      highest separation factor between basic and neutral peptides was obtained at pH 9
      using G-10 membrane with a molecular weight cut-off (MWCO) of 2,500 g/mol, at 5 V
      with the lowest transmembrane pressure (0.344 MPa) and feed velocity (0.047 m/s).
      The transmission behavior of the peptides during EF was better explained when
      taking into account the positive/negative charge ratio. Because of its 3+/1-
      charge ratio, beta-LG 142-148 had the highest transmission during EF.
      Consequently, its relative concentration was raised from 3.5% in the initial
      tryptic beta-LG hydrolysate up to 38% in the permeate. The electric field seemed
      more effective when the convective/shearing forces were minimized.

PMID- 16596668
TI  - A balanced reciprocal translocation in a case of hypomelanosis of Ito with
      confirmation of mosaicism using buccal cell interphase FISH.

PMID- 16596669
TI  - Bilateral periventricular heterotopias in an X-linked dominant transmission in a
      family with two affected males.
AB  - We report on the case of dizygotic twin boys, born prematurely to an asymptomatic
      mother. Bilateral periventricular heterotopias with enlarged ventricles were
      discovered at birth in both twins. One of the twins died prematurely of
      bronchopulmonary complications, and was shown to have several neuropathological
      anomalies (microgyria, thin corpus callosum, and reduced white matter). The
      surviving twin had mental retardation, without epilepsy. MRI of the mother showed
      asymptomatic periventricular heterotopias without ventricular enlargement. She
      had two affected daughters also with asymptomatic periventricular heterotopias. A
      point mutation in the last coding exon 48 of the Filamin A (FLNA) gene (7922c >
      t) was discovered on sequencing and segregated with the affected individuals.
      This family has a classical X-linked dominant BPNH pathology, with greater
      severity in males than females. The location of the FLNA mutation is discussed in
      light of the neuropathological anomalies and mental retardation in male patients.

PMID- 16596670
TI  - FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders
      revisited.
AB  - The recent identification of TGFBR2 mutations in Marfan syndrome II (MFSII)
      [Mizuguchi et al. (2004); Nat Genet 36:855-860] and of TGFBR1 and TGFBR2
      mutations in Loeys-Dietz aortic aneurysm syndrome (LDS) [Loeys et al. (2005); Nat
      Genet 37:275-281] [OMIM 609192] has provided direct evidence of abnormal
      signaling in transforming growth factors beta (TGF-beta) in the pathogenesis of
      Marfan syndrome (MFS). In light of this, we describe the phenotypes and genotypes
      of five individuals. Patient 1 had MFS and abnormal cranial dura. Patient 2 had
      severe early onset MFS and an abnormal skull. Patients 3 and 4 had probable
      Furlong syndrome (FS). Patient 5 had marfanoid (MD) features, mental retardation
      (MR), and a deletion of chromosome 15q21.1q21.3. All patients had a condition
      within the MFS, MD-craniosynostosis (CS) or MD-MR spectrum. The names of these
      entities may become redundant, and instead, come to be considered within the
      spectrum of TGF-beta signaling pathway disorders. Two recurrent heterozygous FBN1
      mutations were found in Patients 1 and 2, and an identical novel heterozygous de
      novo TGFBR1 mutation was found in Patients 3 and 4, in whom altered fibrillin-1
      processing was demonstrated previously [Milewicz et al. (2000); Am J Hum Genet
      67:279]. A heterozygous FBN1 deletion was found in Patient 5. These findings
      support the notion that perturbation of extracellular matrix homeostasis and/or
      remodeling caused by abnormal TGF-beta signaling is the core pathogenetic
      mechanism in MFS and related entities including the MD-CS syndromes.

PMID- 16596671
TI  - Lack of meiotic crossovers during oogenesis in an apparent 45,X Ullrich-Turner
      syndrome patient with three children.
AB  - A woman with apparent 45,X Ullrich-Turner syndrome was ascertained after the
      birth of three girls, the last being growth retarded due to a del(X)(p22.11) of
      grand-paternal origin. In this woman no del(X)-chromosome was detectable in blood
      by FISH or PCR. Fibroblast cultures from four different biopsies of her skin
      varied from having 45,X only to mosaic 46,X,del(X) to 46,X,del(X) only. In one
      fibroblast culture, a few cells with two del(X) chromosomes were found, probably
      remnants of a paternal dicentric X that caused the condition. Her three daughters
      were born when she was 29, 31, and 39 years old, respectively, indicating that
      disomy for the distal half of Xp is not required for normal folliculogenesis.
      When studying the crossover pattern of her daughters' maternal X-chromosomes, it
      turned out that one daughter had an X that was exclusively grand-maternal, one
      daughter lacked crossovers on Xq, and one daughter lacked crossovers on Xp. This
      suggests that univalent X-chromosomes were present in the Ullrich-Turner
      patient's primordial egg cells, either because there was only a single X
      chromosome present (a 45,X primary oocyte), or because the X-chromosome was a
      partially or completely unpaired in pachytene, indicating a problem with
      chromosome association and synapsis formation.

PMID- 16596672
TI  - Literature searches of double trisomy citations are inadequate.

PMID- 16596673
TI  - Thyroid anomalies in Williams syndrome: investigation of 95 patients.
AB  - Thyroid involvement in Williams syndrome (WS) was recently reported in two small
      groups of patients, both showing an increased prevalence of elevation of TSH
      serum concentration; in one of the two reports, 70% of the patients demonstrated
      a hypoplasia of thyroid gland as well. In our institution, we currently follow a
      large population of WS patients who periodically undergo a multispecialist
      clinical evaluation that includes ultrasound evaluation of the thyroid gland, and
      levels of FT3, FT4, TSH, and anti-thyroid antibodies. Here, we report on the
      prevalence of thyroid structural and functional anomalies, in a population of 95
      WS patients, half of them followed for more than 5 years. Our study confirms the
      increased incidence of both elevated TSH serum values (37.9% in our sample) and
      thyroid gland hypoplasia (74.7%). Moreover, we demonstrated that TSH elevation
      declines with age. For this reason, we suggest that a complete thyroid evaluation
      be performed in every patient with WS, and that this medical complication should
      be periodically searched for in follow-up visits.

PMID- 16596674
TI  - Linkage analysis of genetic loci for kyphoscoliosis on chromosomes 5p13, 13q13.3,
      and 13q32.
AB  - Kyphoscoliosis, a three-dimensional deformity of spinal growth, is characterized
      by a curvature in the coronal plane (scoliosis) in conjunction with thoracic
      kyphosis in excess of the normal range in the sagittal plane. We identified
      kyphoscoliosis within members of seven families (53 individuals) originally
      ascertained as part of a large collaborative study of familial idiopathic
      scoliosis. Model-independent linkage analysis of a genome-wide microsatellite
      screen identified areas suggestive of linkage on chromosomes 2q22, 5p13, 13q, and
      17q11. Single-point and multipoint analyses of an additional 25 flanking
      microsatellite markers corroborated linkage to these regions, with areas on
      chromosomes 5p13, 13q13, and 13q32 being the most significant (P < 0.005).
      Analyses of single nucleotide polymorphism (SNP) markers in the candidate region
      on chromosome 5 narrowed the region to approximately 3.5 Mb (P < 0.05), with the
      most significant P values (P < 0.01) occurring in approximately a 1.3-Mb region.
      Candidate loci in this region include IRX1, IRX2, and IRX4 of the Iroquois
      Homeobox protein family. On chromosome 13, single-point and multipoint analyses
      resulted in multiple SNPs having P values < 0.05 within five candidate genes:
      Osteoblast-specific factor 2 or periostin, forkhead box O1A, A-kinase anchor
      protein 11, TBC1 domain family member 4, and glypican 5, thus supporting the
      potential relevance of this region in the pathogenesis of kyphoscoliosis.

PMID- 16596675
TI  - Maternal genotype for the monocyte chemoattractant protein 1 A(-2518)G promoter
      polymorphism is associated with the risk of spina bifida in offspring.

PMID- 16596676
TI  - Genotype-epigenotype-phenotype correlations in females with frontometaphyseal
      dysplasia.
AB  - Frontometaphyseal dysplasia (FMD) belongs to a group of overlapping skeletal
      dysplasias, the common molecular basis of which are mutations of FLNA, the gene
      encoding filamin A. The nature of the mutation has been considered the major
      determinant of the phenotype within this group that comprises the
      otopalatodigital syndromes (OPD1, OPD2) and Melnick-Needles syndrome besides FMD.
      However, to date the molecular pathomechanisms are not well understood. In FMD
      only few FLNA mutations have been reported which do not cluster in a specific
      region of the protein. We report on a novel de novo mutation 5182G --> T in exon
      31 of the FLNA gene in a girl with manifestations of FMD and OPD1. This mutation
      is predicted to lead to the exchange of a highly conserved glycine residue at
      position 1,728 by cysteine (G1728C) in repeat 15 of the filamin A rod domain. In
      a second family with FMD, we identified a known mutation (S1186L) in a mother and
      her son. In contrast to most previous reports on manifesting females or carriers
      of the FLNA-related skeletal dysplasias, the affected females presented here
      showed only mild to moderate skewing of X-inactivation against the mutant allele.
      Our data may indicate that in females, genotype-phenotype correlation between
      certain FLNA mutations and OPD1 and FMD, respectively, is less strict than
      previously assumed. We propose that X-inactivation is an important epigenetic
      modifier of the phenotype in females with the FLNA-related skeletal dysplasias.

PMID- 16596677
TI  - Multicolor banding detects a complex three chromosome, seven breakpoint
      unbalanced rearrangement in an ICSI-derived fetus with multiple abnormalities.
AB  - We describe a fetus from an intracytoplasmic sperm injection (ICSI) pregnancy
      with severe facial clefts, receding jaw, preauricular skin tags, postaxial
      hexadactyly, bi-lobed right lung, supernumerary cranial bone, and dilated lateral
      ventricles of the brain. Using a combination of G-banding, fluorescence in situ
      hybridization (FISH), whole chromosome paints (WCPs), subtelomere probes, and
      multicolor banding (MCB), the karyotype was found to include a de novo unbalanced
      highly complex chromosome rearrangement (hCCR) involving chromosomes 3, 12, and
      15 with seven breakpoints, and including monosomy for two separate regions of
      chromosome 12.

PMID- 16596678
TI  - Meiotic segregation analysis of reciprocal translocations both in sperms and
      blastomeres.
AB  - Balanced chromosomal rearrangements could lead to unbalanced segregation gametes
      during meiosis. In this study, sperm flourescence in situ hybridization (FISH)
      analysis of meiotic segregation products of four reciprocal translocations;
      46,XY,t(7;10)(q21;q22), 46,XY,t(15;17)(q11;p12), 46,XY,t(6;13)(p21.1;q32), and
      46,XY,t(1;13)(q24;q10) are presented. In three out of these four cases with
      t(15;17), t(6;13), and t(1;13) additional blastomere FISH analyses are also
      provided. Multi-color FISH analysis was applied using diverse probe combinations
      specific for translocated chromosome segments. The average frequency of sperm
      nuclei bearing unbalanced products for t(7;10), t(15;17), t(6;13), and t(1;13)
      were 48.7%, 59.5%, 60.5%, and 62.9%, respectively. Frequencies of blastomeres
      comprising unbalanced products in cases with t(15;17), t(6;13), and t(1;13) were
      80% (12 of 15), 60% (3 of 5), and 50% (2 of 4), respectively. Chi-square test
      analysis showed significant differences in the meiotic segregation patterns due
      to the distribution and numbers of the chiasmatas that could depend on the size
      of the translocated segments (P < 0.001). In conclusion, FISH analysis of sperm
      and blastomere for reciprocal translocation carriers effectively estimates the
      approximate risk of unbalanced products and this result might ensure valuable
      genetic counseling.

PMID- 16596679
TI  - Folate gene polymorphisms and the risk of Down syndrome pregnancies in young
      Italian women.
AB  - Maternal impairments in folate metabolism and elevated homocysteinemia are known
      risk factors for having a child with Down syndrome (DS) at a young age. The 80G>A
      polymorphism of the reduced folate carrier gene (RFC-1) has been recently
      demonstrated to affect plasma folate and homocysteine levels, alone or in
      combination with the 677C>T polymorphism in the methylenetetrahydrofolate
      reductase (MTHFR) gene. We performed the present study on 80 Italian mothers of
      DS individuals, aged less than 35 at conception, and 111 Italian control mothers,
      to study the role of the RFC-1 80G>A, MTHFR 677C>T, and MTHFR 1298A>C genotypes
      to the risk of a DS offspring at a young maternal age. When polymorphisms were
      considered alone, both allele and genotype frequencies did not significantly
      differ between DS mothers and control mothers. However, the combined
      MTHFR677TT/RFC-1 80GG genotype was borderline associated with an increased risk
      (OR 6 (CI 95%: 1.0-35.9), P = 0.05), and to be MTHF1298AA/RFC-1 80(GA or AA) was
      inversely associated with the risk (OR 0.36 (CI 95%: 0.14-0.96), P = 0.04).
      Present results seem to indicate that none of the RFC-1 80G>A, MTHFR 677C>T, and
      MTHFR 1298A>C polymorphisms is an independent risk factor for a DS offspring at a
      young maternal age; however, a role for the combined MTHFR/RFC-1 genotypes in the
      risk of DS pregnancies among young Italian women cannot be excluded.

PMID- 16596680
TI  - Crystal structure of the Homo sapiens cytoplasmic ribosomal decoding site
      complexed with apramycin.

PMID- 16596681
TI  - Total chemical synthesis, folding, and assay of a small protein on a water
      compatible solid support.

PMID- 16596682
TI  - Rhodium-catalyzed asymmetric addition of aryl- and alkenylboronic acids to
      isatins.

PMID- 16596683
TI  - Oxidative rearrangements of tricyclic vinylcyclobutane derivatives.
AB  - Three tricyclic vinylcyclobutanes (3-methylenetricyclo[5.3.0.0(2,6)]decanes 1-3)
      have been subjected to ionization by photoinduced electron transfer in solution
      and by X-irradiation in Ar matrices. All three compounds undergo oxidative
      cycloreversion; the cleavage of the four-membered ring, however, occurs in a
      different direction depending on the presence of a methyl group in position 6 of
      the tricyclic framework. In those derivatives, cycloreversion is found to lead to
      1-methyl-8-methylene-1,6-cyclodecadiene radical cations (5.+ from 1, 8.+) from 2)
      which upon back electron transfer yield two different hydrocarbons (6 from 5.+, 9
      from 8.+), depending on the configuration around the endocyclic double bonds of
      the respective cyclodecadiene derivative. In the absence of a methyl group on C6,
      the cycloreversion leads to a radical cation complex between 1-methylenecyclopent
      2-ene and cyclopentene (12.+) which appears to revert to 3 on back electron
      transfer. The intermediate radical cations 5.+, 8.+, and 12.+ have been
      identified and characterized by UV/Vis and IR spectra in Ar matrices. The
      mechanism of their formation is elucidated by quantum chemical calculations.

PMID- 16596684
TI  - Probing the transition between the localised (class II) and localised-to
      delocalised (class II-III) regimes by using intervalence charge-transfer
      solvatochromism in a series of mixed-valence dinuclear ruthenium complexes.
AB  - Intervalence charge-transfer (IVCT) solvatochromism studies on the
      diastereoisomeric forms of [{Ru(bpy)(2)}(2)(mu-BL)](5+) (bpy=2,2'-bipyridine;
      BL=a series of di-bidentate polypyridyl bridging ligands) reveal that the solvent
      dependencies of the IVCT transitions decrease as the "tail" of the bridging
      ligand is extended, and the extent of delocalisation increases. Utilising a
      classical theoretical approach for the analysis of the intervalence charge
      transfer (IVCT) solvatochromism data, the subtle and systematic variation in the
      electronic properties of the bridging ligands can be correlated with the shift
      between the localised (class II) and localised-to-delocalised (class II-III)
      regimes. The investigation of the diastereoisomeric forms of two series of
      complexes incorporating analogous structurally rigid (fused) and nonrigid
      (unfused) bridging ligands demonstrates that the differences in the IVCT
      characteristics of the diastereoisomers of a given complex are accentuated in the
      latter case, due to a stereochemically induced redox asymmetry contribution. The
      marked dependence of the IVCT transitions on the stereochemical identity of the
      complexes provides a quantitative measure of the fundamental contributions of the
      reorganisational energy and redox asymmetry to the intramolecular electron
      transfer barrier at the molecular level.

PMID- 16596685
TI  - Understanding sulfone behavior in palladium-catalyzed domino reactions with aryl
      iodides.
AB  - Unlike traditionally used acyclic 1,2-disubstituted alkenes, the reaction of
      alpha,beta-unsaturated phenyl sulfones with aryl iodides under Heck reaction
      conditions takes place mainly by means of a four-component domino process,
      involving one unit of the alkene and three units of the aryl iodide, affording
      substituted 9-phenylsulfonyl-9,10-dihydrophenanthrenes. We report here the
      results of a computational study on the mechanism of this domino arylation
      reaction. Based on these results we can explain why vinyl sulfones, unlike other
      electron-deficient alkenes such as enones, preferentially follow this domino
      pathway instead of the usual Heck pathway. The key step is a C-H activation
      process in which a five-membered palladacycle is formed. The greater ability of
      vinyl sulfones, relative to enones, to reach the transition state that leads to
      the formation of the initial palladacycle makes the difference.

PMID- 16596686
TI  - Towards clean fuels: molecular-level sulfur reactivity in heavy oils.

PMID- 16596687
TI  - Intramolecular concerted insertion of vinyl cations into C-H bonds:
      hydroalkylating cyclization of alkynes with alkyl chloroformates to give
      cyclopentanes.

PMID- 16596688
TI  - Changing the activity of electrocatalysts for oxygen reduction by tuning the
      surface electronic structure.

PMID- 16596689
TI  - Asymmetric allylic alkylation of cyclic vinylogous esters and thioesters by Pd
      catalyzed decarboxylation of enol carbonate and beta-ketoester substrates.

PMID- 16596691
TI  - Regio- and stereoselective rhodium-catalyzed allylic alkylations of chelated
      enolates.

PMID- 16596690
TI  - Using nonnatural amino acids to control metal-coordination number in three
      stranded coiled coils.

PMID- 16596692
TI  - Highly diastereoselective synthesis of bicyclo[3.2.1]octenones through phosphine
      mediated condensations of 1,4-dien-3-ones.

PMID- 16596693
TI  - Trichloromethyl ketones as synthetically versatile donors: application in direct
      catalytic mannich-type reactions and the stereoselective synthesis of azetidines.

PMID- 16596695
TI  - Water formation on Pt and Pt-based alloys: a theoretical description of a
      catalytic reaction.
AB  - In the past, the modeling of catalytic processes was limited by the size and
      complexity of the systems involved. However, the enormous progress in both
      computer power and theoretical methods has made computational modeling a valuable
      tool in increasing our knowledge of catalytic reactions on the atomic scale.
      While complex reactions can be studied by dividing the overall reaction into a
      series of steps calculable by quantum mechanics, the combination with methods
      appropriate for larger time and length scales enables the gap between these
      regimes to be bridged. This provides a more realistic modeling of the
      experimental system and allows important environmental effects such as solvation
      to be taken into account. In this Minireview we describe some of the main
      theoretical methodologies that are used to study catalytic properties and
      reactions on surfaces. Using these methods, we study the seemingly simple
      reaction of water formation out of hydrogen and oxygen on Pt and Pt/Ni alloy
      catalysts. To provide a more realistic description we also discuss the
      interesting effects determined by hydrating the system or using alloy
      nanoparticles rather than extended surfaces.

PMID- 16596694
TI  - Migration of carbon into subsurface layers of Rh(100): a DFT study.

PMID- 16596697
TI  - Ligand adsorption/desorption on sterically stabilized InP colloidal nanocrystals:
      observation and thermodynamic analysis.

PMID- 16596696
TI  - ESR spin probes in ionic liquids.
AB  - The spin probes 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), 4-hydroxy-2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPOL), and 2,2,6,6-tetramethyl-4
      trimethylammoniumpiperidine-1-oxylIodide (CAT-1) are examined in a number of
      ionic liquids based on substituted imidazolium cations and tetrafluoroborate and
      hexafluorophosphate anions, respectively. The reorientation correlation times
      tau(R) of the spin probes in these systems have been determined by complete
      spectra simulation and, for rapid reortientation, by analysis of the intensities
      of the hyperfine lines of the electron spin resonance (ESR) spectra. A comparison
      of the results with those from the model system glycerol/water and selected
      organic solvents is made. Additions of diamagnetic and paramagnetic ions allow
      the conclusion that salt effects and spin exchange are present, and that both are
      superimposed by motional effects. Specific interactions in the ionic liquids, as
      well as between the spin-probe molecules and the constituents of the ionic
      liquids are reflected in the spectra of the spin probes, depending on their
      molecular structure.

PMID- 16596698
TI  - Thermodynamic and ab initio analysis of the controversial enthalpy of formation
      of formaldehyde.
AB  - There are two values, -26.0 and -27.7 kcal mol(-1), that are routinely reported
      in literature evaluations for the standard enthalpy of formation, Delta(f)
      H(o)(298), of formaldehyde (CH(2)=O), where error limits are less than the
      difference in values. In this study, we summarize the reported literature for
      formaldehyde enthalpy values based on evaluated measurements and on computational
      studies. Using experimental reaction enthalpies for a series of reactions
      involving formaldehyde, in conjunction with known enthalpies of formation, its
      enthalpy is determined to be -26.05+/-0.42 kcal mol(-1), which we believe is the
      most accurate enthalpy currently available. For the same reaction series, the
      reaction enthalpies are evaluated using six computational methods: CBS-Q, CBS
      Q//B3, CBS-APNO, G2, G3, and G3B3 yield Delta(f) H(o)(298)=-25.90+/-1.17 kcal
      mol(-1), which is in good agreement to our experimentally derived result.
      Furthermore, the computational chemistry methods G3, G3MP2B3, CCSD/6
      311+G(2df,p)//B3LYP/6-31G(d), CCSD(T)/6-311+G(2df,p)//B3LYP/6-31G(d), and CBS
      APNO in conjunction with isodesmic and homodesmic reactions are used to determine
      Delta(f) H(o)(298). Results from a series of five work reactions at the higher
      levels of calculation are -26.30+/-0.39 kcal mol(-1) with G3, -26.45+/-0.38 kcal
      mol(-1) with G3MP2B3, -26.09+/-0.37 kcal mol(-1) with CBS-APNO, -26.19+/-0.48
      kcal mol(-1) with CCSD, and -26.16+/-0.58 kcal mol(-1) with CCSD(T). Results from
      heat of atomization calculations using seven accurate ab initio methods yields an
      enthalpy value of -26.82+/-0.99 kcal mol(-1). The results using isodesmic
      reactions are found to give enthalpies more accurate than both other
      computational approaches and are of similar accuracy to atomization enthalpy
      calculations derived from computationally intensive W1 and CBS-APNO methods.
      Overall, our most accurate calculations provide an enthalpy of formation in the
      range of -26.2 to -26.7 kcal mol(-1), which is within computational error of the
      suggested experimental value. The relative merits of each of the three
      computational methods are discussed and depend upon the accuracy of experimental
      enthalpies of formation required in the calculations and the importance of
      systematic computational errors in the work reaction. Our results also calculate
      Delta(f) H(o)(298) for the formyl anion (HCO(-)) as 1.28+/-0.43 kcal mol(-1).

PMID- 16596699
TI  - Electrochemical rate constants in room temperature ionic liquids: the oxidation
      of a series of ferrocene derivatives.

PMID- 16596700
TI  - Protein amyloidogenesis in the context of volume fluctuations: a case study on
      insulin.

PMID- 16596701
TI  - Novel superalkali superhalogen compounds (Li3)+(SH)- (SH=LiF2, BeF3, and BF4)
      with aromaticity: new electrides and alkalides.
AB  - Optimized structures, with all real frequencies, of superalkali superhalides
      (Li(3))(+)(SH)(-) (SH=LiF(2), BeF(3), and BF(4)), are obtained, for the first
      time, at the B3LYP/aug-cc-pVDZ and MP2/aug-cc-pVDZ computational levels. These
      superalkali superhalides possess three characteristics that are significantly
      different from normal alkali halides. 1) They have a variety of structures, which
      come from five bonding mode types: edge-face, edge-edge, face-face, face-edge,
      and staggered face-edge. We find that the bonding mode type closely correlates
      with the Li(3)-SH bond energy. 2) The valence electrons on the Li(3) ring are
      pushed out by the (SH)(-) anion, and become excess electrons, conferring alkalide
      or electride characteristics on these Li(3)-SH species, depending on the bonding
      mode type. 3) The highest occupied molecular orbital of each Li(3)-SH species is
      a doubly occupied delocalized sigma bonding orbital on the Li(3) ring, which
      indicates its aromaticity. It is noticeable that the maximum negative nucleus
      independent chemical shift value (about -10 ppm) moves out from the center of the
      Li(3) ring, owing to repulsion by the SH(-) anion. We find that these superalkali
      superhalides are not only complicated "supermolecules", but are also a new type
      of alkalide or electride, with aromaticity.

PMID- 16596702
TI  - Is current therapy of malignant gliomas beneficial for patients? Proteomics
      evidence of shifts in glioma cells expression patterns under clinically relevant
      treatment conditions.
AB  - The most common human brain tumours - gliomas - have poor prognosis with and
      without treatment. The current therapy conditions act sub-lethally and cannot
      effectively suppress the proliferation of glioma cells. Here we show differential
      protein expression patterns in surviving human malignant U87-MG glioma cells
      under clinically relevant chemo/radiotherapy. In parallel experiments, the cells
      underwent either irradiation (2 Gy, 200 KV X-ray) or chemotreatment with 30
      microg/mL of temozolomide in the cultivation medium or combined chemo/radiation
      treatment. The cell cultures were treated during 5 days from day 4 until day 9 of
      growth. Modulated expression patterns of vimentin and RhoA GTPase indicate a
      potentially increasing grade of malignancy in treated cell fractions correlating
      well with extremely aggressive tumour phenotypes observed clinically at
      recidivation of treated malignant gliomas.

PMID- 16596704
TI  - Modeling a whole organ using proteomics: the avian bursa of Fabricius.
AB  - While advances in proteomics have improved proteome coverage and enhanced
      biological modeling, modeling function in multicellular organisms requires
      understanding how cells interact. Here we used the chicken bursa of Fabricius, a
      common experimental system for B cell function, to model organ function from
      proteomics data. The bursa has two major functional cell types: B cells and the
      supporting stromal cells. We used differential detergent fractionation
      multidimensional protein identification technology (DDF-MudPIT) to identify 5198
      proteins from all cellular compartments. Of these, 1753 were B cell specific,
      1972 were stroma specific and 1473 were shared between the two. By modeling
      programmed cell death (PCD), cell differentiation and proliferation, and
      transcriptional activation, we have improved functional annotation of chicken
      proteins and placed chicken-specific death receptors into the PCD process using
      phylogenetics. We have identified 114 transcription factors (TFs); 42 of the
      bursal B cell TFs have not been reported before in any B cells. We have also
      improved the structural annotation of a newly sequenced genome by confirming the
      in vivo expression of 4006 "predicted", and 6623 ab initio, ORFs. Finally, we
      have developed a novel method for facilitating structural annotation, "expressed
      peptide sequence tags" (ePSTs) and demonstrate its utility by identifying 521
      potential novel proteins from the chicken "unassigned chromosome".

PMID- 16596703
TI  - Proteomic analysis of anaplastic lymphoma cell lines: identification of potential
      tumour markers.
AB  - Anaplastic large-cell lymphomas (ALCL) are high grade lymphomas of T or null
      phenotype often associated with the t(2;5) translocation leading to the
      expression of a chimeric protein consisting of the N-terminal portion of
      nucleophosmin (NPM) and the intracellular domain of the anaplastic lymphoma
      kinase (ALK). Although ALCL are recognized as distinct clinical, biological and
      cytogenetic entities, heterogeneities persist in this group of tumours, which
      exhibit a broad spectrum of morphological features. Particularly, the common type
      tumour consisting in large cells contrast with the small cell variant that is
      sometimes associated with a leukemic phase. The ALK-negative ALCL is often
      associated with a poor prognosis. Here, we investigated the proteome of these
      subtypes of tumours using patient-derived cell lines. We compared the proteome of
      the cytosolic fraction of NPM-ALK-positive versus NPM-ALK-negative cells on one
      hand, and the proteome of common cell type versus small cell variant on the other
      hand. The identification of a set of proteins differentially expressed in the
      subtypes of ALCL points to new diagnosis/prognosis markers. This study also
      provides interesting information on the molecular mechanisms responsible for the
      different subtypes of ALCL.

PMID- 16596705
TI  - Self-assembling protein arrays on DNA chips by auto-labeling fusion proteins with
      a single DNA address.
AB  - The high-throughput deposition of recombinant proteins on chips, beads or
      biosensor devices would be greatly facilitated by the implementation of self
      assembly concepts. DNA-directed immobilization via conjugation of proteins to an
      oligonucleotide would be preeminently suited for this purpose. Here, we present a
      unique method to attach a single DNA address to proteins in one step during the
      purification from the E. coli lysate by fusion to human O6-alkylguanine-DNA
      alkyltransferase (SNAP-tag) and the Avitag. Use of the conjugates in converting a
      DNA chip into a protein chip by self assembly is demonstrated.

PMID- 16596706
TI  - Proteomic characterization of inter-alpha inhibitor proteins from human plasma.
AB  - Inter-alpha inhibitor proteins (IaIp) are a family of structurally related serine
      protease inhibitors found in relatively high concentrations in human plasma.
      Recent studies have implicated a role for IaIp in sepsis, and have demonstrated
      their potential as biomarkers in sepsis and cancer. For characterization of
      isolated IaI proteins and contaminating proteins during the last steps of the
      purification process, SELDI-TOF MS and HPLC-ESI-MS/MS were used. After separation
      by SDS-PAGE or 2-DE, polypeptide bands of 80, 125 and 250 kDa were excised from
      gels and digested by trypsin. The tryptic peptides were analyzed by both MS
      methods. The main contamination during the purification process, a band of 80
      kDa, contains mainly IaIp heavy chain (HC) H3. HC H1 and H2 were also found in
      this band. In addition, some vitamin K-dependent clotting factors and inhibitors
      and other plasma proteins were identified. The 125-kDa band, representing the pre
      alpha inhibitor, was found to contain both bikunin and HC H3. The presence of
      other HC H1, H2 and the recently described HC H4 was also detected by SELDI-TOF
      MS. The presence of HC H1, H2, and H3 in the 125-kDa band was confirmed by ESI
      MS/MS, but not the presence of the H4. Three polypeptides, H1 and H2 together
      with bikunin, were identified in the 250-kDa band, representing the ITI, by both
      MS techniques. Once again, the presence of H4 was detected in this band only by
      SELDI-TOF MS, but the number of corresponding peptides was still not sufficient
      for final identification of this polypeptide. The importance of the application
      of proteomic methods for the proper evaluation of therapeutic drugs based on
      human plasma is discussed.

PMID- 16596708
TI  - Characterization of the SDS-induced electroosmotic flow in micellar
      electrokinetic chromatography with cationic polyelectrolyte-coated capillaries.
AB  - Manipulation of the EOF is essential for achieving optimal separations by MEKC.
      In this paper, we present an extensive investigation of the effect of common
      experimental conditions on the EOF observed in a capillary coated with
      poly(diallyldimethylammonium chloride) (PDADMA) polyelectrolyte under MEKC
      conditions. It was found that highly reproducible cathodal EOF is achieved
      approximately at or just below the conditional CMC value of SDS in the
      electrolytes used. At concentrations of SDS greater than the CMC the EOF is
      independent of pH. The impact of common organic modifiers (ACN, methanol, urea,
      beta-CD and nonionic surfactant) on the EOF behavior in both a PDADMA-coated
      capillary and a bare silica capillary is compared. The suppressing effect of
      organic modifiers on the EOF is much stronger for coated capillary indicating
      that these compounds additionally reduce the negative charge density on the
      capillary surface due to alteration of the surfactant coating.

PMID- 16596707
TI  - Development of a "reverse capture" autoantibody microarray for studies of antigen
      autoantibody profiling.
AB  - Diagnosing cancers based on serum profiling is a particularly attractive concept.
      However, the technical challenges to analysis of the serum proteome arise from
      the dynamic range of protein amounts. Cancer sera contain antibodies that react
      with a unique group of autologous cellular antigens, which affords a dramatic
      amplification of signal in the form of antibodies relative to the amount of the
      corresponding antigens. The serum autoantibody repertoire from cancer patients
      might, therefore, be exploited for antigen-antibody profiling. To date, studies
      of antigen-antibody reactivity using microarrays have relied on recombinant
      proteins or synthetic peptides as arrayed features. However, recombinant proteins
      and/or synthetic peptides may fail to accurately detect autoantibody binding due
      to the lack of proper PTMs. Here we describe the development and use of a
      "reverse capture" autoantibody microarray. Our "reverse capture" autoantibody
      microarray is based on the dual-antibody sandwich immunoassay platform of ELISA,
      which allows the antigens to be immobilized in their native configuration. As
      "proof-of-principle", we demonstrate its use for antigen-autoantibody profiling
      with sera from patients with prostate cancer and benign prostate hyperplasia.

PMID- 16596709
TI  - Picoliter-volume aqueous droplets in oil: electrochemical detection and yeast
      cell electroporation.
AB  - An electrochemical detection method was introduced for aqueous droplet analysis
      in oil phase of microfluidic devices. This method is based on the electrochemical
      signal difference between aqueous and oil. Applying a low alternating current
      (AC) voltage to a couple of Au microelectrodes, this method can offer size
      information and ion concentration range from 0.02 mmol/L to 1 mol/L of tens of
      picoliter to nanoliter aqueous droplets. Alternatively, applying a relative high
      AC voltage (18 Vpp) at a frequency of 1 kHz leads to electroporation of yeast
      cells encapsulated into picoliter droplets. We believe that this simple technique
      is useful for a number of aqueous droplet-based chemical and biological analyses
      as well as cell electroporation.

PMID- 16596711
TI  - Insights into human CD34+ hematopoietic stem/progenitor cells through a
      systematically proteomic survey coupled with transcriptome.
AB  - Hematopoietic stem cells are capable of self-renewal and differentiation into
      different hematopoietic lineages. To gain a comprehensive understanding of
      hematopoietic stem/progenitor cells, a systematic proteomic survey of human CD34+
      cells collected from human umbilical cord blood was performed, in which the
      proteins were separated by 1- and 2-DE, as well as by nano-LC, and subsequently
      identified by MS. A total of 370 distinct proteins identified from those cells
      provided new insights into the potential of the stem/progenitor cells because the
      nerve, gonad, and eye-associated proteins were reliably identified.
      Interestingly, the transcripts of 133 (35.9%) identified proteins were not found
      by the prevalent transcriptome approaches, although several selected transcripts
      could be detected by RT-PCR. Moreover, the heterogeneity of 33 proteins
      identified from 2-DE was attributable primarily to post-translational processes
      rather than to alternative splicing at transcriptional level. Furthermore, the
      biosyntheses of 15 proteins identified in this study appears not to be completely
      interrupted in spite of the fact that corresponding antisense RNAs were found in
      the existing transcriptome data. The integrated proteomic and transcriptomic
      analyses employed here provided a unique view of the human stem/progenitor cells.

PMID- 16596712
TI  - Potential protein markers for nutritional health effects on colorectal cancer in
      the mouse as revealed by proteomics analysis.
AB  - It is suggested that colorectal cancer might be prevented by changes in diet, and
      vegetable consumption has been demonstrated to have a protective effect. Until
      now, little is known about the effects of vegetable consumption at the proteome
      level. Therefore, the effect of increased vegetable intake on the protein
      expression in the colonic mucosa of healthy mice was studied. Aim was to identify
      the proteins that are differentially expressed by increased vegetable consumption
      and to discriminate their possible role in the protection against colorectal
      cancer. Mice were fed four different vegetable diets, which was followed by
      analysis of total cellular protein from colonic mucosal cells by a combination of
      2-DE and MS. We found 30 proteins that were differentially expressed in one or
      more diets as compared to the control diet. Six could be identified by MALDI-TOF
      MS: myosin regulatory light chain 2, carbonic anhydrase I, high-mobility group
      protein 1, pancreatitis-associated protein 3, glyceraldehyde-3-phosphate
      dehydrogenase and ATP synthase oligomycin sensitivity conferral protein.
      Alterations in the levels of these proteins agree with a role in the protection
      against colon cancer. We conclude that these proteins are suitable markers for
      the health effect of food on cancer. The observed altered protein levels
      therefore provide support for the protective effects of vegetables against
      colorectal cancer.

PMID- 16596713
TI  - Proteomic analysis of primary cell lines identifies protein changes present in
      renal cell carcinoma.
AB  - New markers/targets for renal cell carcinoma (RCC) are needed to enable earlier
      detection and monitoring of disease and therapeutic targeting. To identify such
      molecules, normal and RCC-derived primary cell lines have been used as a
      simplified model system for studying changes that accompany tumorigenesis. Short
      term cultures allow enrichment of relevant cell types from tissue samples, which
      is balanced against the potential for in vitro changes. Examination of 3 proteins
      with altered expression in RCC tissue showed the maintenance of normal-tumour
      differences in culture, although some changes were apparent, including alteration
      in the isoform of aldolase. Comparative analysis of primary cell lines by 2-DE
      found 43 proteins up-regulated and 29 down-regulated in at least three out of
      five tumour cell lines. Many of the observed changes have been previously
      reported in RCC, including up-regulation of several glycolytic enzymes, vimentin
      and heat shock protein 27, validating the approach. Additionally, several novel
      changes in protein expression were found, including up-regulation of several
      proteins involved in actin cytoskeleton organisation such as radixin and moesin,
      two members of the septin family, and the actin bundling protein, fascin.
      Validation studies using Western blotting and immunohistochemistry indicate that
      several of these molecules may be useful as markers for RCC.

PMID- 16596715
TI  - HIV and minorities. CDC: AIDS awareness is crucial to survival of black
      communities.

PMID- 16596714
TI  - Quantitative proteome analysis of breast cancer cell lines using 18O-labeling and
      an accurate mass and time tag strategy.
AB  - Proteome comparison of cell lines derived from cancer and normal breast
      epithelium provide opportunities to identify differentially expressed proteins
      and pathways associated with specific phenotypes. We employed 16O/18O peptide
      labeling, FT-ICR MS, and an accurate mass and time (AMT) tag strategy to
      simultaneously compare the relative abundance of hundreds of proteins in non
      cancer and cancer cell lines derived from breast tissue. A cell line reference
      panel allowed relative protein abundance comparisons among multiple cell lines
      and across multiple experiments. A peptide database generated from
      multidimensional LC separations and MS/MS analysis was used for subsequent AMT
      tag-based peptide identifications. This peptide database represented a total of
      2299 proteins, including 514 that were quantified in five cell lines using the
      AMT tag and 16O/18O strategies. Eighty-six proteins showed at least a threefold
      protein abundance change between cancer and non-cancer cell lines. Hierarchical
      clustering of protein abundance ratios revealed that several groups of proteins
      were differentially expressed between the cancer cell lines.

PMID- 16596717
TI  - Discrimination. Lambda launches Web site for "Blow the Whistle" campaign.

PMID- 16596716
TI  - Transmission. 10th Circuit upholds ban on exotic dancers.

PMID- 16596718
TI  - Greatest hits. By Caveman.

PMID- 16596719
TI  - Improving a nation's cardiac health. Interview by Judy Ozkan, BA.

PMID- 16596720
TI  - History of cardiology: Mackenzie's ink polygraph.

PMID- 16596721
TI  - Special issue: Judith Hall Festschrift.

PMID- 16596722
TI  - Chronic in vivo hypoxia in various organs: hypoxia-inducible factor-1alpha and
      apoptosis.
AB  - We studied the in vivo persistence of hypoxia-inducible factor-1alpha (HIF
      1alpha), main transducer of hypoxia, the differential response in organs exposed
      to the same degree of hypoxemia and the relationship with apoptosis. We measured
      HIF-1alpha (immunohistochemistry peroxidase and Western blot) and apoptosis
      (TUNEL) in heart, liver, kidney, gastrocnemius, and brain of rats exposed to
      chronic normobaric hypoxia (10% O2) or normoxia (21% O2) for 2 weeks. Despite
      same arterial O2 pressure and increased hemoglobin concentration (219 +/- 5 vs.
      124 +/- 4 g/L), the organs responded differently. While marked in brain, muscle,
      and kidney cortex, HIF-1alpha was undetectable in heart and liver. In kidney
      medulla, HIF-1alpha was high in both normoxia and hypoxia. By contrast, apoptosis
      was marked in heart, slight in kidney medulla, and undetectable in other organs.
      We conclude that the HIF-1alpha response to chronic hypoxia can be a sustained
      phenomenon, but not in all organs, and that apoptosis responds differently from
      HIF-1alpha.

PMID- 16596724
TI  - Discrimination. Grievance trips up inmate's HIV-discrimination claim.

PMID- 16596723
TI  - The phosphoinositide 3-kinase/Akt-signal pathway mediates proliferation and
      secretory function of hepatic sinusoidal endothelial cells in rats after partial
      hepatectomy.
AB  - OBJECTIVE: To investigate the role of AKT signaling pathway in hepatic sinusoidal
      endothelial cells (SECs) early after partial hepatectomy in rats and the
      regulatory mechanisms involved. METHODS: The animal model of 70% hepatectomy was
      made. Hepatic SECs were isolated and cultured according to Braet et al.'s method
      with some modifications. The cultured hepatic SECs were divided into two groups:
      70% partial hepatectomy groups and LY294002 group (LY). We observed the
      expressions of AKT and NF-kappaB in cultured hepatic SECs by Western blot,
      measured the levels of NO, NOs, IL-6, and HGF in the supernatants of hepatic SEC
      cultures and [3H]thymidine incorporation, and analyzed cell cycle of cultured
      hepatic SECs by flow cytometer. The relationship of the Akt pathway with
      secretions and proliferation of hepatic SECs after partial hepatectomy was
      probed. RESULTS: The levels of Akt protein expression increased significantly
      after partial hepatectomy in OG group and with a peak at 24 h post operation.
      Meanwhile, there was a markedly increase in phosphorylated Akt protein during 2
      72 h after operation. But the expression and activity of Akt protein did not
      change significantly after partial hepatectomy in the LY group. So, partial
      hepatectomy can marked induce Akt expression and result in rapid and marked
      phosphorylation of Akt from 2 to 72 h thereafter. The changes of NF-kappaB
      expression in cultured hepatic SECs were similar to those of Akt expression after
      operation. The concentrations of HGF and IL-6 in the supernatants of cultured
      hepatic SECs were relatively low in the LY group, and were markedly increased
      after partial hepatectomy, with a peak at 24 h in the OG group. There were
      significant differences between the OG and LY groups at 6 and 24 h (P < 0.05).
      Both NO and NOS secretion was increased in the OG group compared to the LY group
      within 24 h after partial hepatectomy. But the secretion of NO and NOS was
      increased more markedly in the LY group than that in the OG beyond 24 h. These
      findings suggest that the secretion of the cytokines by hepatic SECs is mediated
      by Akt signaling. Akt signaling pathway in relationship with proliferation of
      hepatic SECs and suppression of apoptosis. In OG group, the hepatic SECs in S and
      G2/M obviously increased. The proliferative index of hepatic SECs in OG group had
      significant differences with that in LY group at 6, 24, and 72 h, P < 0.05.
      Meanwhile, the cells of apoptosis in OG group were very low, and the cells in LY
      group gradually increased. CONCLUSIONS: These results suggest that AKT signaling
      pathway plays a crucial role in mediating proliferating and secreted signals in
      hepatic SECs. AKT has been suggested to play a pivotal role in early liver
      regeneration involved in the induction of secreted cytokines and proliferation of
      hepatic SECs.

PMID- 16596725
TI  - Medical need prevails over consent in HIV testing case.

PMID- 16596726
TI  - SSI. Commissioner granted chance to remedy man's record.

PMID- 16596727
TI  - Global. State Department praises PEPFAR results in annual report.

PMID- 16596728
TI  - HIV drug resistance and you.  Using resistance testing in clinical practice. U.S.
      guidelines, cost, limitations--and usefulness.

PMID- 16596729
TI  - HIV drug resistance and you. The limitations of drug resistance testing. Many
      factors influence the results.

PMID- 16596730
TI  - HIV drug resistance and you. Resistance testing in experienced patients.
      Considerations when changing drugs.

PMID- 16596731
TI  - Roundtable. Who should be providing HIV care?

PMID- 16596733
TI  - On Medicare.

PMID- 16596732
TI  - American Association of Clinical Endocrinologists and Associazione Medici
      Endocrinologi medical guidelines for clinical practice for the diagnosis and
      management of thyroid nodules.
AB  - Thyroid nodules are common and are frequently benign. Current data suggest that
      the prevalence of palpable thyroid nodules is 3% to 7% in North America; the
      prevalence is as high as 50% based on ultrasonography (US) or autopsy data. The
      introduction of sensitive thyrotropin (thyroid-stimulating hormone or TSH)
      assays, the widespread application of fine-needle aspiration (FNA) biopsy, and
      the availability of high-resolution US have substantially improved the management
      of thyroid nodules. This document was prepared as a collaborative effort between
      the American Association of Clinical Endocrinologists (AACE) and the Associazione
      Medici Endocrinologi (AME). Most Task Force members are members of AACE. We have
      used the AACE protocol for clinical practice guidelines, with rating of available
      evidence, linking the guidelines to the strength of recommendations. Key
      observations include the following. Although most patients with thyroid nodules
      are asymptomatic, occasionally patients complain of dysphagia, dysphonia,
      pressure, pain, or symptoms of hyperthyroidism or hypothyroidism. Absence of
      symptoms does not rule out a malignant lesion; thus, it is important to review
      risk factors for malignant disease. Thyroid US should not be performed as a
      screening test. All patients with a palpable thyroid nodule, however, should
      undergo US examination. US-guided FNA (US-FNA) is recommended for nodules > or =
      10 mm; US-FNA is suggested for nodules < 10 mm only if clinical information or US
      features are suspicious. Thyroid FNA is reliable and safe, and smears should be
      interpreted by an experienced pathologist. Patients with benign thyroid nodules
      should undergo follow-up, and malignant or suspicious nodules should be treated
      surgically. A radioisotope scan of the thyroid is useful if the TSH level is low
      or suppressed. Measurement of serum TSH is the best initial laboratory test of
      thyroid function and should be followed by measurement of free thyroxine if the
      TSH value is low and of thyroid peroxidase antibody if the TSH value is high.
      Percutaneous ethanol injection is useful in the treatment of cystic thyroid
      lesions; large,symptomatic goiters may be treated surgically or with radioiodine.
      Routine measurement of serum calcitonin is not recommended. Suggestions for
      thyroid nodule management during pregnancy are presented. We believe that these
      guidelines will be useful to clinical endocrinologists, endocrine surgeons,
      pediatricians, and internists whose practices include management of patients with
      thyroid disorders. These guidelines are thorough and practical, and they offer
      reasoned and balanced recommendations based on the best available evidence.

PMID- 16596735
TI  - [Uncommon complications in central venous catheterization].

PMID- 16596736
TI  - [Extrapulmonary sarcoidosis as a cause of chronic liver disease. Report of one
      case].

PMID- 16596737
TI  - [Angioimmunoblastic T-cell lymphoma: a case report and review of the literature].

PMID- 16596738
TI  - [Subclavian venous thrombosis and pulmonary thromboembolism as manifestation of
      type II heparin-induced thrombocytopenia].

PMID- 16596739
TI  - [Non-Hodgkin lymphoma and renal cell carcinoma].

PMID- 16596741
TI  - [Bacteriemia caused by Staphylococcus cohnii associated with acute
      cholecystitis].

PMID- 16596740
TI  - Improved somatic growth following adenoidectomy and tonsillectomy in young
      children. Possible pathogenetic mechanisms.
AB  - The effect of Adenotonsillectomy on somatic growth was studied prospectively in
      57, randomly selected children (31 boys, 26 girls), aged 5.03+/-1.32 (mean+/-1SD)
      years. The indication for surgery was adenotonsillar hypertrophy with or without
      recurrent infections. Weight, height, triceps skinfold thickness, and Body Mass
      Index were measured prior to the operation and 6-13 months afterwards. Weight was
      significantly improved following T&A in all children. The improvement in height
      was significantly only for children under 5 years. In an attempt to uncover the
      pathogenetic mechanisms, lactic acid, pyruvic acid, somatomedin-C (IGF-I), growth
      hormone(GH), insulin, glucose, pH, hemoglobin (Hbeta). and white cell count (WBC)
      were also determined in the last 18 children, prior to and 6-8 months post
      operatively. For the comparison of pre and post operative values the paired t
      test was applied. Although the values of GH and IGF1 did not significantly
      increase post-op the IGF-1/GH ratio increased, possibly indicating improved IGF1
      generation. There was also a rise in Hbeta values and a lowering of WBC, probably
      reflecting the lower frequency of infections. All other metabolic indices did not
      change. In conclusion, linear grow post-Adenotonsillectomy improved in children
      aged <5 years and was associated with improved with IGF-1/GH ratio, increased
      Hbeta values and decreased in WBC.

PMID- 16596742
TI  - Medicare program; conditions for payment of power mobility devices, including
      power wheelchairs and power-operated vehicles. Final rule.
AB  - This final rule conforms our regulations to section 302(a)(2)(E)(iv) of the
      Medicare Prescription Drug, Improvement, and Modernization Act of 2003. This rule
      defines the term power mobility devices (PMDs) as power wheelchairs and power
      operated vehicles (POVs or scooters). It sets forth revised conditions for
      Medicare payment of PMDs and defines who may prescribe PMDs. This rule also
      requires a face-to-face examination of the beneficiary by the physician or
      treating practitioner, a written prescription, and receipt of pertinent parts of
      the medical record by the supplier within 45 days after the face-to-face
      examination that the durable medical equipment suppliers maintain in their
      records and make available to CMS or its agents upon request. Finally, this rule
      discusses CMS' policy on documentation that may be requested by CMS or its agents
      to support a Medicare claim for payment, as well as the elimination of the
      Certificate of Medical Necessity (CMN) for PMDs.

PMID- 16596743
TI  - Career education: an application of latent growth curve modelling to career
      information-seeking behaviour of school pupils.
AB  - BACKGROUND: This study applied the theory of planned behaviour (TPB) in an
      attempt to predict longitudinal growth of career exploratory behaviour in school
      pupils. The importance of information for making considered career decisions is
      indicated in theories of career development and choice, career education
      programmes, and concepts of career maturity. AIMS: The study aimed to initially
      model individual and group levels of career exploratory behaviour and then to
      identify psychological variables that predicted such behaviour. SAMPLE:
      Longitudinal data from a sample of 325 adolescents (mean age 16.4 years, SD =
      0.77, 45% were male) was collected at three points in time. METHOD: A latent
      growth curve model was specified to account for initial status and subsequent
      linear growth of career exploratory behaviour. Variables representing the TPB
      were included in the model to explain the variation in the intercept and slope
      factors. RESULTS: The latent growth curve model was found to be an acceptable
      description of the data, and indicated that there was significant individual
      variability in terms of the intercept and slope factors. Behavioural intention
      was found to be a significant predictor of the intercept factor, but not of the
      slope factor. CONCLUSIONS: It was concluded that the TPB remains a useful
      theoretical framework from which to explain career information-seeking behaviour.

PMID- 16596745
TI  - Bibliography. Current world literature. Valvular heart disease.

PMID- 16596746
TI  - Bibliography. Current world literature. Heart transplantation.

PMID- 16596744
TI  - Commentary: where and how could biomarkers be used in 2016?
AB  - Since the beginning of the human genome project there has been considerable
      speculation about how this resource and the knowledge creation it enabled would
      change therapeutic discovery, development, and delivery. As the project neared
      completion, considerable claims and predictions were made about the changes that
      soon would be forthcoming. Many of these early predictions failed to materialize,
      however, leading to further speculation about the reasons, including the role of
      the pharmaceutical industry in realizing the promise of "genomic medicine."
      During this same period, considerable strides were made in other areas of
      molecular biology and medicine, and in response scientific thinking naturally
      evolved. Researchers and regulators moved from a genotype-centric view to a view
      that all biomarkers are potential tools to improve drug development and
      therapeutic decision making. Molecular biology is now seen as encouraging more
      "personalized medicine"-the closer alignment of biological information (derived
      from molecular diagnostics) and therapy selection. Meanwhile, there are growing
      concerns that increasing expenditures in pharmaceutical research and development
      are not sustainable and not reaping sufficient gains for shareholders or society
      at large. Thus, there is new speculation about how biomarkers, personalized
      medicine, and the industry will interact and create value for patients. This
      overview seeks to explore the issues driving pharmaceutical productivity and the
      likely contribution of biomarkers in the future.

PMID- 16596747
TI  - Micro3D: computer program for three-dimensional reconstruction visualization, and
      analysis of neuronal populations and barin regions.
AB  - This article presents a computer program, Micro3D, designed for 3-D
      reconstruction, visualization, and analysis of coordinate-data (points and lines)
      recorded from serial sections. The software has primarily been used for studying
      shapes and dimension of brain regions (contour line data) and distributions of
      cellular elements such as neuronal cell bodies or axonal terminal fields labeled
      with tract-tracing techniques (point data). The tissue elements recorded could
      equally well be labeled with use of other techniques, the only requirement being
      that the data collected are saved as x,y,z coordinates. Data are typically
      imported from image-combining computerized microscopy systems or image analysis
      systems, such as Neurolucida (MicroBrightField, Colchester, VT) or analySIS (Soft
      Imaging System, Gmbh, Munster, Germany). System requirements are a PC running
      LINUX. Reconstructions in Micro3D may be rotated and zoomed in real-time, and
      submitted to perspective viewing and stereo-imaging. Surfaces are re-synthesized
      on the basis of stacks of contour lines. Clipping is used for defining section
      independent subdivisions of the reconstruction. Flattening of curved sheets of
      points layers (e.g., neurons in a layer) facilitates inspection of complicated
      distribution patterns. Micro3D computes color-coded density maps. Opportunities
      for translation of data from different reconstructions into common coordinate
      systems are also provided. This article demonstrates the use of Micro3D for
      visualization of complex neuronal distribution patterns in somatosensory and
      auditory systems. The software is available for download on conditions posted at
      the NeSys home pages (http://www.nesys.uio.no/) and at The Rodent Brain Workbench
      (http://www.rbwb.org/).

PMID- 16596749
TI  - Vaccines and veterinarians to tackle the spread of avian influenza.

PMID- 16596748
TI  - Engineered bio-nanocapsules, the selective vector for drug delivery system.
AB  - The bio-nanocapsule (BNC) is our concept of artificial hollow nanoparticles that
      have been designed and produced through biotechnological procedures. We proposed
      an empty virus-like particle, which consists of a recombinant L envelope protein
      of hepatitis B virus (HBV) and a lipid derived from the host cell, as an
      engineered BNC. Although this BNC was first developed as an immunogen of
      hepatitis B vaccine, the pre-S1 region in N-terminus of L envelope protein
      confers hepatocyte specific infectivity of HBV on the BNC. This recombinant BNC
      is now being developed as a novel platform of drug delivery system (DDS) vector
      for selective delivery.

PMID- 16596750
TI  - The Partial-Birth Abortion Ban Act of 2003.

PMID- 16596751
TI  - The need for increased oversight of genetic testing: a detailed look at the
      genetic testing process.

PMID- 16596752
TI  - Rights discourse and mandatory HIV testing of pregnant women and newborns.

PMID- 16596753
TI  - Tell me a story: using short fiction in teaching law and bioethics.

PMID- 16596754
TI  - Will the "right to die" become a license to kill? The growth of euthanasia in
      America.

PMID- 16596755
TI  - The Oregon Death with Dignity Act: review and proposals for improvement.

PMID- 16596756
TI  - "O wind, remind him that I have no child": infertility and feminist
      jurisprudence.

PMID- 16596757
TI  - Increasing the global exchange of evidence-based research.

PMID- 16596759
TI  - Challenging medical decision-making: professional dominance, patient rights or
      collaborative autonomy?

PMID- 16596758
TI  - Reproductive liberty under the threat of care: deputizing private agents and
      deconstructing state action.

PMID- 16596760
TI  - Buy baby: the European Union and regulation of human reproduction.
AB  - In its decision in ex parte Blood the Court of Appeal relied on European
      Community (EC) law to hold that the Human Fertilization and Embryology Authority
      had acted unlawfully in taking its decision to prevent Mrs Blood from exporting
      sperm taken from her dying husband without his written consent. The Blood case
      raises the issue of the extent to which EC law may affect the regulation of human
      reproduction in the Member States. Responding to fears that such national
      regulation might be 'swept away' by the commodifying nature of EC law, this
      article considers the scope of the potential application of EC law to regulation
      of human reproduction. The cautious conclusion is that, while there may be some
      increase in deregulatory pressures, the 'vertical relationship' of supreme EC law
      to national law may turn out to be less significant than 'horizontal
      relationships' between policy-makers within and between the EU and its Member
      States.

PMID- 16596761
TI  - Abortion, autonomy and prenatal diagnosis.
AB  - The principle of patient self-determination has assumed central importance in
      British medical law in recent years. This article considers whether this
      increasingly strong commitment to patient autonomy has any resonance for abortion
      law. In particular, this article explores the possibility that the priority
      currently accorded to autonomous decision making may be in tension with the
      Abortion Act's requirement that a woman's reasons for seeking to terminate her
      pregnancy be judged acceptable by two medical practitioners. Moreover, interest
      in the moral legitimacy of a woman's reasons for wanting to terminate her
      pregnancy seems to be intensifying. Concerns arising from the increasing
      availability of precise prenatal tests have led to suggestions that access to
      abortion should be further restricted in order to prevent the cavalier use of
      abortion for reasons that might seem trivial or misguided. Using abortion
      following prenatal diagnosis as an example, this article considers whether it is
      anomalous for the common law's vigorous protection of an individual's freedom to
      make irrational or morally objectionable choices about his or her medical
      treatment to coexist with demands for further restriction of the acceptable
      grounds for abortion.

PMID- 16596762
TI  - New collaborations with native Americans in the conduct of community research.

PMID- 16596764
TI  - Different and differenced takes on disparities.

PMID- 16596763
TI  - Clinical studies in the intensive care unit: ethical and legal aspects.
AB  - This article draws on international experience to explore the ethical and legal
      aspects of performing clinical studies on patients in intensive care units. It
      discusses aspects of consent relevant to clinical studies in this medical
      environment, it considers the involvement of ethical committees, and the role and
      appropriate level of intensive cover.

PMID- 16596765
TI  - Journey through the courts: minors, abortion and the quest for reproductive
      fairness.

PMID- 16596766
TI  - Bird flu.

PMID- 16596767
TI  - Final report of the safety assessment of niacinamide and niacin.
AB  - Niacinamide (aka nicotinamide) and Niacin (aka nicotinic acid) are heterocyclic
      aromatic compounds which function in cosmetics primarily as hair and skin
      conditioning agents. Niacinamide is used in around 30 cosmetic formulations
      including shampoos, hair tonics, skin moisturizers, and cleansing formulations.
      Niacin is used in a few similar product types. The concentration of use of
      Niacinamide varies from a low of 0.0001% in night preparations to a high of 3% in
      body and hand creams, lotions, powders and sprays. Niacin concentrations of use
      range from 0.01% in body and hand creams, lotions, powders and sprays to 0.1% in
      paste masks (mud packs). Both ingredients are accepted for use in cosmetics in
      Japan and the European Union. Both are GRAS direct food additives and nutrient
      and/or dietary supplements. Niacinamide may be used in clinical treatment of
      hypercholesteremia and Niacin in prevention of pellegra and treatment of certain
      psychological disorders. Both ingredients are readily absorbed from skin, blood,
      and the intestines and widely distribute throughout the body. Metabolites include
      N1-methylnicotinamide and N1-methyl-4-pyridone-3-carboxamide. Excretion is
      primarily through the urinary tract. While Niacinamide is more toxic than Niacin
      in acute toxicity studies, both are relatively non-toxic. Short-term oral,
      parenteral, or dermal toxicity studies did not identify significant irreversible
      effects. Niacinamide, evaluated in an in vitro test to predict ocular irritation,
      was not an acute ocular hazard. Animal testing of Niacinamide in rabbits in
      actual formulations produced mostly non-irritant reactions, with only some
      marginally irritating responses. Skin irritation tests of up to 2.5% Niacinamide
      in rabbits produced only marginal irritation. Skin sensitization tests of
      Niacinamide at 5% during induction and 20% during challenge were negative in
      guinea pigs. Neither cosmetic ingredient was mutagenic in Ames tests, with or
      without metabolic activation. Niacinamide and Niacin at 2 mg/ml were negative in
      a chromosome aberration test in Chinese hamster ovary cells, but did produce
      large structural chromosome aberrations at 3 mg/ml. Niacinamide induced sister
      chromatid exchanges in Chinese hamster ovary cells, but Niacin did not. Under
      certain circumstances, Niacinamide can cause an increase in unscheduled DNA
      synthesis in human lymphocytes treated with UV or a nitrosoguanidine compound.
      Niacinamide itself was not carcinogenic when administered (1%) in the drinking
      water of mice. No data on the carcinogenic effect of Niacin were available.
      Niacinamide can moderate the induction of tumors by established carcinogens.
      Niacinamide in combination with streptozotocin (a nitrosourea compound) or with
      heliotrine (a pyrrolizidine alkaloid), produced pancreatic islet tumors. On the
      other hand, Niacinamide reduced the renal adenomas produced by streptozotocin;
      and intestinal and bladder tumors induced by a preparation of bracken fern.
      Niacinamide evaluated in in vitro test systems did affect development, but
      Niacinamide reduced the reproductive/developmental toxicity of 2
      aminonicotinamide-amino-1,3,4-thiadiazole hydrochloride and urethane. Clinical
      testing of Niacinamide produced no stinging sensation at concentrations up to
      10%, use tests produced no irritation at concentrations up to 5%, and a 21-day
      cumulative irritation test at concentrations up to 5% resulted in no irritancy.
      Niacinamide was not a sensitizer, nor was it a photosensitizer. The CIR Expert
      Panel considered that Niacinamide and Niacin are sufficiently similar from a
      toxicologic standpoint to combine the available data and reach a conclusion on
      the safety of both as cosmetic ingredients. Overall, these ingredients are non
      toxic at levels considerably higher than would be experienced in cosmetic
      products. Clinical testing confirms that these ingredients are not significant
      skin irritants, sensitizers or photosensitizers. While certain formulations were
      marginal to slight ocular irritants, other formulations were not. Niacinamide,
      while not carcinogenic alone, can modulate the induction of tumors by certain
      established carcinogens. The Panel noted that the doses in these studies are high
      relative to the low concentrations at which Niacinamide is used in cosmetic
      formulations. In neither case (tumor protection or tumor promotion) are these
      findings considered relevant to the use of Niacinamide at its current low
      concentrations of use in cosmetics. Both ingredients were considered safe as used
      in cosmetics.

PMID- 16596768
TI  - Final report of the safety assessment of methacrylic acid.
AB  - Methacrylic Acid is an organic acid used at concentrations between 50 and 88
      percent to pretreat the nail and maximize the adhesion between the nail and
      artificial nail extender. Methacrylic Acid is readily absorbed through mucous
      membranes of the lungs, the gastrointestinal tract, and the skin; and is
      distributed to all major tissues. Oral LD50 values for rats ranged from 277 to
      2260 mg/kg; acute toxicity symptoms included severe gastric irritation, gasping,
      labored respiration, prostration and hematuria. In a short-term inhalation study,
      rats exposed to Methacrylic Acid at 1300 ppm showed nose and eye irritation and
      weight loss, while necropsy results and blood and urine tests were normal.
      Methacrylic Acid is an ocular toxicant in animals. Undiluted Methacrylic Acid is
      corrosive to the skin of rabbits and guinea pigs. Exposure as limited as 3
      minutes can cause severe erythema and slight to moderate edema. Exposure from 15
      minutes to 24 hours under occlusive patches can cause marked to severe
      discoloration, slight to severe subcutaneous hemorrhages, necrosis, ulcerations,
      severe erythema, edema and concave eschar. Methacrylic Acid was irritating and
      caused strong rubefaction and scab formation in a guinea pig maximization test at
      challenge concentrations from 10 to 100 percent. It was difficult to determine if
      the results were type IV hypersensitivity reactions or simple irritation. In
      three other studies, guinea pigs were not sensitized. Methacrylic Acid was not a
      reproductive/developmental toxicant in rats or mice. Methacrylic Acid was
      negative in Salmonella typhimurium mutagenicity tests using strains TA98, TA100,
      TA1535 and TA1537 both with and without metabolic activation, but was positive in
      a DNA-cell-binding assay. Case reports involving Methacrylic Acid often involve
      children. Effects from ingestion include drooling, gagging, and vomiting.
      Children exposed to Methacrylic Acid as a result of accidental spills caused
      first and second degree burns to the eyes, face, hands, arms, and chest. The
      Consumer Product Safety Commission has required child-resistant packaging for
      liquid household products containing more than 5 percent Methacrylic Acid (weight
      to-volume) in a single package. Since Methacrylic Acid is an extremely corrosive
      chemical, a primary concern about its use as a cosmetic ingredient was the
      ability to limit exposure to the nail when pretreating the nail prior to
      application of an artificial nail extender. A videotape presentation demonstrated
      that a trained professional could use a small applicator brush to dab a limited
      volume of Methacrylic Acid only to the center of the nail, allowing the monomer
      liquid to diffuse down the nail without any exposure to the skin. There were no
      available data to demonstrate that an individual consumer could apply Methacrylic
      Acid and avoid inadvertent skin contact. In order to minimize any exposure to the
      acid, the Expert Panel concluded that nail primers containing Methacrylic Acid
      could be used safely by trained individuals instructed to ensure that there be no
      contact with the skin. The CIR Expert Panel recognized that there are no chronic
      inhalation toxicity data on Methacrylic Acid, but was concerned that inhalation
      of Methacrylic Acid could affect the respiratory tract. Since the inhalation
      exposure time is significantly increased in a commercial setting, the Panel was
      more concerned about the safety of the nail technician than the consumer. The
      Expert Panel concluded that the current NIOSH recommended exposure limit of 20
      ppm would provide adequate protection.

PMID- 16596769
TI  - Final report of the safety assessment of methacrylate ester monomers used in nail
      enhancement products.
AB  - Methacrylate ester monomers are used in as artificial nail builders in nail
      enhancement products. They undergo rapid polymerization to form a hard material
      on the nail that is then shaped. While Ethyl Methacrylate is the primary monomer
      used in nail enhancement products, other methacrylate esters are also used. This
      safety assessment addresses 22 other methacrylate esters reported by industry to
      be present in small percentages as artificial nail builders in cosmetic products.
      They function to speed up polymerization and/or form cross-links. Only
      Tetrahydrofurfuryl Methacrylate was reported to the FDA to be in current use. The
      polymerization rates of these methacrylate esters are within the same range as
      Ethyl Methacrylate. While data are not available on all of these methacrylate
      esters, the available data demonstrated little acute oral, dermal, or i.p.
      toxicity. In a 28-day inhalation study on rats, Butyl Methacrylate caused upper
      airway irritation; the NOAEL was 1801 mg/m3. In a 28-day oral toxicity study on
      rats, t-Butyl Methacrylate had a NOAEL of 20 mg/kg/day. Beagle dogs dosed with
      0.2 to 2.0 g/kg/day of C12 to C18 methacrylate monomers for 13 weeks exhibited
      effects only in the highest dose group: weight loss, emesis, diarrhea, mucoid
      feces, or salivation were observed. Butyl Methacrylate (0.1 M) and Isobutyl
      Methacrylate (0.1 M) are mildly irritating to the rabbit eye. HEMA is corrosive
      when instilled in the rabbit eye, while PEG-4 Dimethacrylate and
      Trimethylolpropane Trimethacrylate are minimally irritating to the eye. Dermal
      irritation caused by methacrylates is documented in guinea pigs and rabbits. In
      guinea pigs, HEMA, Isopropylidenediphenyl Bisglycidyl Methacrylate, Lauryl
      Methacrylate, and Trimethylolpropane Trimethacrylate are strong sensitizers;
      Butyl Methacrylate, Cyclohexyl Methacrylate, Hexyl Methacrylate, and Urethane
      Methacrylate are moderate sensitizers; Hydroxypropyl Methacrylate is a weak
      sensitizer; and PEG-4 Dimethacrylate and Triethylene Glycol Dimethacrylate are
      not sensitizers. Ethylene Glycol Dimethacrylate was not a sensitizer in one
      guinea pig study, but was a strong sensitizer in another. There is cross
      reactivity between various methacrylate esters in some sensitization tests.
      Inhaled Butyl Methacrylate, HEMA, Hydroxypropyl Methacrylate, and
      Trimethylolpropane Trimethacrylate can be developmental toxicants at high
      exposure levels (1000 mg/kg/day). None of the methacrylate ester monomers that
      were tested were shown to have any endocrine disrupting activity. These
      methacrylate esters are mostly non-mutagenic in bacterial test systems, but weak
      mutagenic responses were seen in mammalian cell test systems. Chronic dermal
      exposure of mice to PEG-4 Dimethacrylate (25 mg, 2 x weekly for 80 weeks) or
      Trimethylolpropane Trimethacrylate (25 mg, 2 x weekly for 80 weeks) did not
      result in increased incidence of skin or visceral tumors. The carcinogenicity of
      Triethylene Glycol Dimethacrylate (5, 25, or 50%) was assessed in a mouse skin
      painting study (50 microl for 5 days/week for 78 weeks), but was not carcinogenic
      at any dose level tested. The Expert Panel was concerned about the strong
      sensitization and crossor co-reactivity potential of the methacrylate esters
      reviewed in this report. However, data demonstrated the rates of polymerization
      of these Methacrylates were similar to that of Ethyl Methacrylate and there would
      be little monomer available exposure to the skin. In consideration of the animal
      toxicity data, the CIR Expert Panel decided that these methacrylate esters should
      be restricted to the nail and must not be in contact with the skin. Accordingly,
      these methacrylate esters are safe as used in nail enhancement products when skin
      contact is avoided.

PMID- 16596770
TI  - Pharmacological actions of cannabinoids.
AB  - Mammalian tissues express at least two types of cannabinoid receptor, CB1 and
      CB2, both G protein coupled. CB1 receptors are expressed predominantly at nerve
      terminals where they mediate inhibition of transmitter release. CB2 receptors are
      found mainly on immune cells, one of their roles being to modulate cytokine
      release. Endogenous ligands for these receptors (endocannabinoids) also exist.
      These are all eicosanoids; prominent examples include arachidonoylethanolamide
      (anandamide) and 2-arachidonoyl glycerol. These discoveries have led to the
      development of CB1- and CB2-selective agonists and antagonists and of bioassays
      for characterizing such ligands. Cannabinoid receptor antagonists include the CB1
      selective SR141716A, AM251, AM281 and LY320135, and the CB2-selective SR144528
      and AM630. These all behave as inverse agonists, one indication that CB1 and CB2
      receptors can exist in a constitutively active state. Neutral cannabinoid
      receptor antagonists that seem to lack inverse agonist properties have recently
      also been developed. As well as acting on CB1 and CB2 receptors, there is
      convincing evidence that anandamide can activate transient receptor potential
      vanilloid type 1 (TRPV1) receptors. Certain cannabinoids also appear to have non
      CB1, non-CB2, non-TRPV1 targets, for example CB2-like receptors that can mediate
      antinociception and "abnormal-cannabidiol" receptors that mediate vasorelaxation
      and promote microglial cell migration. There is evidence too for TRPV1-like
      receptors on glutamatergic neurons, for alpha2-adrenoceptor-like (imidazoline)
      receptors at sympathetic nerve terminals, for novel G protein-coupled receptors
      for R-(+)-WIN55212 and anandamide in the brain and spinal cord, for novel
      receptors for delta9-tetrahydrocannabinol and cannabinol on perivascular sensory
      nerves and for novel anandamide receptors in the gastro-intestinal tract. The
      presence of allosteric sites for cannabinoids on various ion channels and non
      cannabinoid receptors has also been proposed. In addition, more information is
      beginning to emerge about the pharmacological actions of the non-psychoactive
      plant cannabinoid, cannabidiol. These recent advances in cannabinoid pharmacology
      are all discussed in this review.

PMID- 16596771
TI  - Cannabinoid receptor signaling.
AB  - The cannabinoid receptor family currently includes two types: CB1, characterized
      in neuronal cells and brain, and CB2, characterized in immune cells and tissues.
      CB1 and CB2 receptors are members of the superfamily of seven-transmembrane
      spanning (7-TM) receptors, having a protein structure defined by an array of
      seven membrane-spanning helices with intervening intracellular loops and a C
      terminal domain that can associate with G proteins. Cannabinoid receptors are
      associated with G proteins of the Gi/o family (Gi1, 2 and 3, and Go1 and 2).
      Signal transduction via Gi inhibits adenylyl cyclase in most tissues and cells,
      although signaling via Gs stimulates adenylyl cyclase in some experimental
      models. Evidence exists for cannabinoid receptor-mediated Ca2+ fluxes and
      stimulation of phospholipases A and C. Stimulation of CB1 and CB2 cannabinoid
      receptors leads to phosphorylation and activation of p42/p44 mitogen-activated
      protein kinase (MAPK), p38 MAPK and Jun N-terminal kinase (JNK) as signaling
      pathways to regulate nuclear transcription factors. The CB1 receptor regulates K+
      and Ca2+ ion channels, probably via Go. Ion channel regulation serves as an
      important component of neurotransmission modulation by endogenous cannabinoid
      compounds released in response to neuronal depolarization. Cannabinoid receptor
      signaling via G proteins results from interactions with the second, third and
      fourth intracellular loops of the receptor. Desensitization of signal
      transduction pathways that couple through the G proteins probably entails
      phosphorylation of critical amino acid residues on these intracellular surfaces.

PMID- 16596773
TI  - Analysis of the endocannabinoid system by using CB1 cannabinoid receptor knockout
      mice.
AB  - The endocannabinoid system has been involved in the control of several
      neurophysiological and behavioural responses. To date, three lines of CB1
      knockout mice have been established independently in different laboratories. This
      chapter reviews the main results obtained with these lines of CB1 knockout mice
      in several physiological responses that have been previously related to the
      activity of the endocannabinoid system. Studies using CB1 knockout mice have
      demonstrated that this receptor participates in the control of several
      behavioural responses including locomotion, anxiety- and depressive-like states,
      cognitive functions such as memory and learning processes, cardiovascular
      responses and feeding. Furthermore, the CB1 cannabinoid receptor is involved in
      the control of pain by acting at peripheral, spinal and supraspinal levels. The
      involvement of the CB1 cannabinoid receptor in the behavioural and biochemical
      processes underlying drug addiction has also been investigated. These CB1
      knockouts have provided new findings to clarify the interactions between
      cannabinoids and the other drugs of abuse such as opioids, psychostimulants,
      nicotine and ethanol. Recent studies have demonstrated that endocannabinoids can
      function as retrograde messengers, modulating the release of different
      neurotransmitters, including opioids, gamma-aminobutyric acid (GABA), and
      cholecystokinin (CCK), which could explain some of the responses observed after
      the stimulation of the CB1 cannabinoid receptor. This review provides an update
      of the apparently controversial data reported in the literature using the three
      different lines of CB1 knockout mice, which seem to be mainly due to the use of
      different experimental procedures rather than any constitutive alteration in
      these lines of knockouts.

PMID- 16596772
TI  - Molecular biology of cannabinoid receptors.
AB  - To date, two cannabinoid receptors have been isolated by molecular cloning. The
      CB1 and CB2 cannabinoid receptors are members of the G protein-coupled receptor
      family. There is also evidence for additional cannabinoid receptor subtypes. The
      CB1 and CB2 receptors recognize endogenous and exogenous cannabinoid compounds,
      which fall into five structurally diverse classes. Mutagenesis and molecular
      modeling studies have identified several key amino acid residues involved in the
      selective recognition of these ligands. Numerous residues involved in receptor
      activation have been elucidated. Regions of the CB1 receptor mediating
      desensitization and internalization have also been discovered. The known genetic
      structures of the CB1 and CB2 receptors indicate polymorphisms and multiple exons
      that maybe involved in tissue and species-specific regulation of these genes. The
      cannabinoid receptors are regulated during chronic agonist exposure, and gene
      expression is altered in disease states. There is a complex molecular
      architecture of the cannabinoid receptors that allows a single receptor to
      recognize multiple classes of compounds and produce an array of distinct
      downstream effects.

PMID- 16596774
TI  - The biosynthesis, fate and pharmacological properties of endocannabinoids.
AB  - The finding of endogenous ligands for cannabinoid receptors, the
      endocannabinoids, opened a new era in cannabinoid research. It meant that the
      biological role of cannabinoid signalling could be finally studied by
      investigating not only the pharmacological actions subsequent to stimulation of
      cannabinoid receptors by their agonists, but also how the activity of these
      receptors was regulated under physiological and pathological conditions by
      varying levels of the endocannabinoids. This in turn meant that the enzymes
      catalysing endocannabinoid biosynthesis and inactivation had to be identified and
      characterized, and that selective inhibitors of these enzymes had to be developed
      to be used as (1) probes to confirm endocannabinoid involvement in health and
      disease, and (2) templates for the design of new therapeutic drugs. This chapter
      summarizes the progress achieved in this direction during the 12 years following
      the discovery of the first endocannabinoid.

PMID- 16596775
TI  - Modulators of endocannabinoid enzymic hydrolysis and membrane transport.
AB  - Tissue concentrations of the endocannabinoids N-arachidonoylethanolamine (AEA)
      and 2-arachidonoylglycerol (2-AG) are regulated by both synthesis and
      inactivation. The purpose of this review is to compile available data regarding
      three inactivation processes: fatty acid amide hydrolase, monoacylglycerol
      lipase, and cellular membrane transport. In particular, we have focused on
      mechanisms by which these processes are modulated. We describe the in vitro and
      in vivo effects of inhibitors of these processes as well as available evidence
      regarding their modulation by other factors.

PMID- 16596776
TI  - Structural requirements for cannabinoid receptor probes.
AB  - The discovery and cloning of CB1 and CB2, the two known G(i/o) protein-coupled
      cannabinoid receptors, as well as the isolation and characterization of two
      families of endogenous cannabinergic ligands represented by
      arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG), have
      opened new horizons in this newly discovered field of biology. Furthermore, a
      considerable number of cannabinoid analogs belonging to structurally diverse
      classes of compounds have been synthesized and tested, thus providing substantial
      information on the structural requirements for cannabinoid receptor recognition
      and activation. Experiments with site-directed mutated receptors and computer
      modeling studies have suggested that these diverse classes of ligands may
      interact with the receptors through different binding motifs. The information
      about the exact binding site may be obtained with the help of suitably designed
      molecular probes. These ligands either interact with the receptors in a
      reversible fashion (reversible probes) or alternatively attach at or near the
      receptor active site with the formation of covalent bonds (irreversible probes).
      This review focuses on structural requirements of cannabinoid receptor ligands
      and highlights their pharmacological and therapeutic potential.

PMID- 16596777
TI  - Cannabinoid receptors and their ligands: ligand-ligand and ligand-receptor
      modeling approaches.
AB  - The cannabinoid CB1 and CB2 receptors belong to the class A, rhodopsin-like
      family of GPCRs. Antagonists for each receptor sub-type, as well as four
      structural classes of agonists that bind to both receptors, have been identified.
      An extensive amount of structure-activity relationship information (SAR) has been
      developed for agonists and antagonists that bind at CB1, while the SAR of CB2
      ligands is only now emerging in the literature. This chapter focuses both on
      recent CB1 and CB2 SAR and on the pharmacophores for ligand recognition at the
      CB1 receptor that have been developed using ligand-ligand or ligand-receptor
      approaches. In a ligand-ligand approach, the structure of the binding site of the
      ligand is not directly considered. This approach is an attempt to infer
      information about the macromolecular binding site, and/or modes of binding
      interactions from a correlation between experimentally determined biological
      activities and the structural and electronic features of a series of small
      molecules. In a ligand-receptor approach, cannabinoid (CB) receptor models are
      probed for ligand binding sites and binding sites can be screened using energetic
      criteria, as well as ligand SAR and the CB mutation literature. This chapter
      discusses the factors that control the quality of the results emanating from each
      of these approaches and identifies areas of agreement and of disagreement in the
      existing CB literature. Challenges for future SAR and pharmacophore development
      are also identified.

PMID- 16596778
TI  - The phylogenetic distribution and evolutionary origins of endocannabinoid
      signalling.
AB  - The endocannabinoid signalling system in mammals comprises several molecular
      components, including cannabinoid receptors (e.g. CB1, CB2), putative endogenous
      ligands for these receptors [e.g. anandamide, 2-arachidonoylglycerol (2-AG)] and
      enzymes involved in the biosynthesis and inactivation of anandamide (e.g. NAPE
      PLD, FAAH) and 2-AG (e.g. DAG lipase, MGL). In this review we examine the
      occurrence of these molecules in non-mammalian organisms (in particular, animals
      and plants) by surveying published data and by basic local alignment search tool
      (BLAST) analysis of the GenBank database and of genomic sequence data from
      several vertebrate and invertebrate species. We conclude that the ability of
      cells to synthesise molecules that are categorised as "endocannabinoids" in
      mammals is an evolutionarily ancient phenomenon that may date back to the
      unicellular common ancestor of animals and plants. However, exploitation of these
      molecules for intercellular signalling may have occurred independently in
      different lineages during the evolution of the eukaryotes. The CB1- and CB2-type
      receptors that mediate effects of endocannabinoids in mammals occur throughout
      the vertebrates, and an orthologue of vertebrate cannabinoid receptors was
      recently identified in the deuterostomian invertebrate Ciona intestinalis
      (CiCBR). However, orthologues of the vertebrate cannabinoid receptors are not
      found in protostomian invertebrates (e.g. Drosophila, Caenorhabditis elegans).
      Therefore, it is likely that a CB1/CB2-type cannabinoid receptor originated in a
      deuterostomian invertebrate. This phylogenetic information provides a basis for
      exploitation of selected non-mammalian organisms as model systems for research on
      endocannabinoid signalling.

PMID- 16596779
TI  - Distribution of cannabinoid receptors in the central and peripheral nervous
      system.
AB  - CB1 cannabinoid receptors appear to mediate most, if not all of the psychoactive
      effects of delta-9-tetrahydrocannabinol and related compounds. This G protein
      coupled receptor has a characteristic distribution in the nervous system: It is
      particularly enriched in cortex, hippocampus, amygdala, basal ganglia outflow
      tracts, and cerebellum--a distribution that corresponds to the most prominent
      behavioral effects of cannabis. In addition, this distribution helps to predict
      neurological and psychological maladies for which manipulation of the
      endocannabinoid system might be beneficial. CB1 receptors are primarily expressed
      on neurons, where most of the receptors are found on axons and synaptic
      terminals, emphasizing the important role of this receptor in modulating
      neurotransmission at specific synapses. While our knowledge of CB1 localization
      in the nervous system has advanced tremendously over the past 15 years, there is
      still more to learn. Particularly pressing is the need for (1) detailed
      anatomical studies of brain regions important in the therapeutic actions of drugs
      that modify the endocannabinoid system and (2) the determination of the
      localization of the enzymes that synthesize, degrade, and transport the
      endocannabinoids.

PMID- 16596780
TI  - Effects of cannabinoids on neurotransmission.
AB  - The CB1 cannabinoid receptor is widely distributed in the central and peripheral
      nervous system. Within the neuron, the CB1 receptor is often localised in axon
      terminals, and its activation leads to inhibition of transmitter release. The
      consequence is inhibition of neurotransmission via a presynaptic mechanism.
      Inhibition of glutamatergic, GABAergic, glycinergic, cholinergic, noradrenergic
      and serotonergic neurotransmission has been observed in many regions of the
      central nervous system. In the peripheral nervous system, CB1 receptor-mediated
      inhibition of adrenergic, cholinergic and sensory neuroeffector transmission has
      been frequently observed. It is characteristic for the ubiquitous operation of
      CB1 receptor-mediated presynaptic inhibition that antagonistic components of
      functional systems (for example, the excitatory and inhibitory inputs of the same
      neuron) are simultaneously inhibited by cannabinoids. Inhibition of voltage
      dependent calcium channels, activation of potassium channels and direct
      interference with the synaptic vesicle release mechanism are all implicated in
      the cannabinoid-evoked inhibition of transmitter release. Many presynaptic CB1
      receptors are subject to an endogenous tone, i.e. they are constitutively active
      and/or are continuously activated by endocannabinoids. Compared with the abundant
      data on presynaptic inhibition by cannabinoids, there are only a few examples for
      cannabinoid action on the somadendritic parts of neurons in situ.

PMID- 16596781
TI  - Retrograde signalling by endocannabinoids.
AB  - The cannabinoid neurotransmitter system comprises cannabinoid G protein-coupled
      membrane receptors (CB1 and CB2), endogenous cannabinoids (endocannabinoids), as
      well as mechanisms for their synthesis, membrane transport and metabolism. Within
      the brain the marijuana constituent delta9-tetrahydrocannabinol (THC) produces
      its pharmacological actions by acting on cannabinoid CB1 receptors. THC modulates
      neuronal excitability by inhibiting synaptic transmission via presynaptic CB1
      mediated mechanisms. More recently, it has been established that physiological
      stimulation of neurons can induce the synthesis of endocannabinoids, which also
      modulate synaptic transmission via cannabinoid CB1 and other receptor systems.
      These endogenously synthesised endocannabinoids appear to act as retrograde
      signalling agents, reducing synaptic inputs onto the stimulated neuron in a
      highly selective and restricted manner. In this review we describe the cellular
      mechanisms underlying retrograde endocannabinoid signalling.

PMID- 16596782
TI  - Effects on the immune system.
AB  - Marijuana and other exogenous cannabinoids alter immune function and decrease
      host resistance to microbial infections in experimental animal models and in
      vitro. Two modes of action by which delta9-tetrahydrocannabinol (THC) and other
      cannabinoids affect immune responses have been proposed. First, cannabinoids may
      signal through the cannabinoid receptors CB1 and CB2. Second, at sites of direct
      exposure to high concentrations of cannabinoids, such as the lung, membrane
      perturbation may be involved. In addition, endogenous cannabinoids or
      endocannabinoids have been identified and have been proposed as native modulators
      of immune functions through cannabinoid receptors. Exogenously introduced
      cannabinoids may disturb this homoeostatic immune balance. A mode by which
      cannabinoids may affect immune responses and host resistance maybe by perturbing
      the balance of T helper (Th)1 pro-inflammatory versus Th2 anti-inflammatory
      cytokines. While marijuana and various cannabinoids have been documented to alter
      immune functions in vitro and in experimental animals, no controlled longitudinal
      epidemiological studies have yet definitively correlated immunosuppressive
      effects with increased incidence of infections or immune disorders in humans.
      However, cannabinoids by virtue of their immunomodulatory properties have the
      potential to serve as therapeutic agents for ablation of untoward immune
      responses.

PMID- 16596783
TI  - Imaging of the brain cannabinoid system.
AB  - This review covers two major strategies for imaging of the brain cannabinoid
      system: autoradiography and in vivo neuroimaging. Cannabinoid receptors can be
      imaged directly with autoradiography in brain slices using radiolabeled
      cannabinoid receptor ligands. In addition, the effects of pharmacologic doses of
      unlabeled cannabinoid drugs can be autoradiographically imaged using indicators
      of blood flow or indicators of metabolism such as glucose analogs. Although
      cannabinoid imaging is a relatively new topic of research compared to imaging of
      other drugs of abuse, autoradiographic strategies have produced high-quality
      information about the distribution of brain cannabinoid receptors and the effects
      of cannabinoid drugs on brain metabolism. In vivo neuroimaging, in contrast to
      autoradiography, utilizes noninvasive techniques such as positron emission
      tomography (PET), single photon emission computed tomography (SPECT), and
      magnetic resonance imaging (MRI) to image both the binding and the effects of
      drugs within living brain. These techniques are well developed; however, in vivo
      imaging of cannabinoid systems is in a very preliminary state. Early results have
      been promising yet hard to generalize. Definitive answers to some of the most
      important questions about cannabinoid drugs and their effects await development
      of suitable in vivo neuroimaging ligands for cannabinoid systems.

PMID- 16596784
TI  - Cannabinoid function in learning, memory and plasticity.
AB  - Marijuana and its psychoactive constituents induce a multitude of effects on
      brain function. These include deficits in memory formation, but care needs to be
      exercised since many human studies are flawed by multiple drug abuse, small
      sample sizes, sample selection and sensitivity of psychological tests for subtle
      differences. The most robust finding with respect to memory is a deficit in
      working and short-term memory. This requires intact hippocampus and prefrontal
      cortex, two brain regions richly expressing CB1 receptors. Animal studies, which
      enable a more controlled drug regime and more constant behavioural testing, have
      confirmed human results and suggest, with respect to hippocampus, that exogenous
      cannabinoid treatment selectively affects encoding processes. This may be
      different in other brain areas, for instance the amygdala, where a predominant
      involvement in memory consolidation and forgetting has been firmly established.
      While cannabinoid receptor agonists impair memory formation, antagonists reverse
      these deficits or act as memory enhancers. These results are in good agreement
      with data obtained from electrophysiological recordings, which reveal reduction
      in neural plasticity following cannabinoid treatment, and increased plasticity
      following antagonist exposure. The mixed receptor properties of the
      pharmacological tool, however, make it difficult to define the exact role of any
      CB1 receptor population in memory processes with any certainty. This makes it all
      the more important that behavioural studies use selective administration of drugs
      to specific brain areas, rather than global administration to whole animals. The
      emerging role of the endogenous cannabinoid system in the hippocampus may be to
      facilitate the induction of long-term potentiation/the encoding of information.
      Administration of exogenous selective CB1 agonists may therefore disrupt
      hippocampus-dependent learning and memory by 'increasing the noise', rather than
      'decreasing the signal' at potentiated inputs.

PMID- 16596785
TI  - Cannabinoid control of motor function at the basal ganglia.
AB  - Classic and novel data strengthen the idea of a prominent role for the
      endocannabinoid signaling system in the control of movement. This finding is
      supported by three-fold evidence: (1) the abundance of the cannabinoid CB1
      receptor subtype, but also of CB2 and vanilloid VR1 receptors, as well as of
      endocannabinoids in the basal ganglia and the cerebellum, the areas that control
      movement; (2) the demonstration of a powerful action, mostly of an inhibitory
      nature, of plant-derived, synthetic, and endogenous cannabinoids on motor
      activity, exerted by modulating the activity of various classic
      neurotransmitters; and (3) the occurrence of marked changes in endocannabinoid
      transmission in the basal ganglia of humans affected by several motor disorders,
      an event corroborated in animal models of these neurological diseases. This three
      fold evidence has provided support to the idea that cannabinoid-based compounds,
      which act at key steps of the endocannabinoid transmission [receptors,
      transporter, fatty acid amide hydrolase (FAAH)], might be of interest because of
      their potential ability to alleviate motor symptoms and/or provide
      neuroprotection in a variety of neurological pathologies directly affecting basal
      ganglia structures, such as Parkinson's disease and Huntington's chorea, or
      indirectly, such as multiple sclerosis and Alzheimer's disease. The present
      chapter will review the knowledge on this issue, trying to establish future lines
      for research into the therapeutic potential of the endocannabinoid system in
      motor disorders.

PMID- 16596786
TI  - Cannabinoid mechanisms of pain suppression.
AB  - A large body of literature indicates that cannabinoids suppress behavioral
      responses to acute and persistent noxious stimulation in animals. This review
      examines neuroanatomical, behavioral, and neurophysiological evidence supporting
      a role for cannabinoids in suppressing pain at spinal, supraspinal, and
      peripheral levels. Localization studies employing receptor binding and
      quantitative autoradiography, immunocytochemistry, and in situ hybridization are
      reviewed to examine the distribution of cannabinoid receptors at these levels and
      provide a neuroanatomical framework with which to understand the roles of
      endogenous cannabinoids in sensory processing. Pharmacological and transgenic
      approaches that have been used to study cannabinoid antinociceptive mechanisms
      are described. These studies provide insight into the functional roles of
      cannabinoid CB1 (CB1R) and CB2 (CB2R) receptor subtypes in cannabinoid
      antinociceptive mechanisms, as revealed in animal models of acute and persistent
      pain. The role of endocannabinoids and related fatty acid amides that are
      implicated in endogenous mechanisms for pain suppression are discussed. Human
      studies evaluating therapeutic potential of cannabinoid pharmacotherapies in
      experimental and clinical pain syndromes are evaluated. The potential of
      exploiting cannabinoid antinociceptive mechanisms in novel pharmacotherapies for
      pain is discussed.

PMID- 16596787
TI  - Effects of cannabinoids on hypothalamic and reproductive function.
AB  - Marijuana and cannabinoids have been shown to exert profound effects on
      hypothalamic regulatory functions and reproduction in both experimental animals
      and humans. Here we review the role of (endo)cannabinoids in the regulation of
      appetite and food intake. There is converging evidence that the hypothalamic
      endocannabinoid system changes after leptin treatment. Cannabinoid administration
      decreases heat production by altering hypothalamic neurotransmitter production.
      Experimental and human data have also shown that the endocannabinoid system is
      involved in the regulation of reproductive function at both central and
      peripheral levels. We discuss also the role of fatty acid amide hydrolase (FAAH)
      in gestation, and in particular the regulation of the activity of FAAH by
      progesterone and leptin. We show that endocannabinoids inhibit the release of
      leukaemia inhibitory factor (LIF) from peripheral T lymphocytes. Taken together,
      endocannabinoids not only help to maintain neuroendocrine homeostasis, but also
      take part in immunological changes occurring during early pregnancy.

PMID- 16596788
TI  - Cannabinoids and the digestive tract.
AB  - In the digestive tract there is evidence for the presence of high levels of
      endocannabinoids (anandamide and 2-arachidonoylglycerol) and enzymes involved in
      the synthesis and metabolism of endocannabinoids. Immunohistochemical studies
      have shown the presence of CB1 receptors on myenteric and submucosal nerve
      plexuses along the alimentary tract. Pharmacological studies have shown that
      activation of CB1 receptors produces relaxation of the lower oesophageal
      sphincter, inhibition of gastric motility and acid secretion, as well as
      intestinal motility and secretion. In general, CB1-induced inhibition of
      intestinal motility and secretion is due to reduced acetylcholine release from
      enteric nerves. Conversely, endocannabinoids stimulate intestinal primary sensory
      neurons via the vanilloid VR1 receptor, resulting in enteritis and enhanced
      motility. The endogenous cannabinoid system has been found to be involved in the
      physiological control of colonic motility and in some pathophysiological states,
      including paralytic ileus, intestinal inflammation and cholera toxin-induced
      diarrhoea. Cannabinoids also possess antiemetic effects mediated by activation of
      central and peripheral CB1 receptors. Pharmacological modulation of the
      endogenous cannabinoid system could provide a new therapeutic target for the
      treatment of a number of gastrointestinal diseases, including nausea and
      vomiting, gastric ulcers, secretory diarrhoea, paralytic ileus, inflammatory
      bowel disease, colon cancer and gastro-oesophageal reflux conditions.

PMID- 16596790
TI  - Effects on cell viability.
AB  - Cannabinoids are known to control the cell survival/death decision, leading to
      different outcomes that depend on the nature of the target cell and its
      proliferative or differentiation status. Cannabinoids induce growth arrest or
      apoptosis in a number of transformed cells in culture. They do so by modulating
      key cell signalling pathways involved in the control of tumour cell fate. The
      best-characterised example is cannabinoid-induced apoptosis of glioma cells,
      which occurs via sustained ceramide accumulation, extracellular signal-regulated
      kinase activation and Akt inhibition. In addition, cannabinoid administration
      inhibits the angiogenesis and slows the growth of different types of tumours in
      laboratory animals. By contrast, most of the experimental evidence indicates that
      cannabinoids protect normal neurons and glial cells from apoptosis as induced by
      toxic insults such as glutamatergic overstimulation, ischaemia and oxidative
      damage. It is therefore very likely that cannabinoids regulate cell survival and
      cell death pathways differently in tumour and non-tumour cells. Regarding immune
      cells, cannabinoids affect proliferation and survival in a complex and still
      obscure manner that depends on the experimental setting. The findings reviewed
      here might set the basis for the use of cannabinoids in the treatment of cancer
      and neurodegenerative diseases.

PMID- 16596792
TI  - Pharmacokinetics and metabolism of the plant cannabinoids, delta9
      tetrahydrocannabinol, cannabidiol and cannabinol.
AB  - Increasing interest in the biology, chemistry, pharmacology, and toxicology of
      cannabinoids and in the development of cannabinoid medications necessitates an
      understanding of cannabinoid pharmacokinetics and disposition into biological
      fluids and tissues. A drug's pharmacokinetics determines the onset, magnitude,
      and duration of its pharmacodynamic effects. This review of cannabinoid
      pharmacokinetics encompasses absorption following diverse routes of
      administration and from different drug formulations, distribution of analytes
      throughout the body, metabolism by different tissues and organs, elimination from
      the body in the feces, urine, sweat, oral fluid, and hair, and how these
      processes change over time. Cannabinoid pharmacokinetic research has been
      especially challenging due to low analyte concentrations, rapid and extensive
      metabolism, and physicochemical characteristics that hinder the separation of
      drugs of interest from biological matrices--and from each other--and lower drug
      recovery due to adsorption of compounds of interest to multiple surfaces. delta9
      Tetrahydrocannabinol, the primary psychoactive component of Cannabis sativa, and
      its metabolites 11-hydroxy-delta9-tetrahydrocannabinol and 11-nor-9-carboxy
      tetrahydrocannabinol are the focus of this chapter, although cannabidiol and
      cannabinol, two other cannabinoids with an interesting array of activities, will
      also be reviewed. Additional material will be presented on the interpretation of
      cannabinoid concentrations in human biological tissues and fluids following
      controlled drug administration.

PMID- 16596791
TI  - Effects on development.
AB  - This chapter will review the effects produced on neural development by maternal
      consumption of cannabinoids during gestation and lactation, with emphasis in the
      maturation of several neurotransmitter systems (dopamine, serotonin, opioids,
      cannabinoids, etc.) and possible modifications in their functional expression at
      the behavioral or neuroendocrine levels. In addition, we have analyzed the
      possible existence of a sexual dimorphism in these ontogenic effects of
      cannabinoids, as well as the possible molecular mechanism underlying such
      effects. In general, the results discussed support the view that exposure to
      cannabinoids during critical periods of development produces marked modifications
      in the functional expression of diverse neuronal systems in adulthood.
      Furthermore, the functions of endocannabinoids in the brain are large not only in
      adulthood, but also in the period of prenatal and postnatal development. Thus,
      endocannabinoids have been reported to be present in early ages and to play a
      role in the process of brain development: neural proliferation and migration,
      axonal elongation, synaptogenesis and/or myelogenesis.

PMID- 16596789
TI  - Cardiovascular pharmacology of cannabinoids.
AB  - Cannabinoids and their synthetic and endogenous analogs affect a broad range of
      physiological functions, including cardiovascular variables, the most important
      component of their effect being profound hypotension. The mechanisms of the
      cardiovascular effects of cannabinoids in vivo are complex and may involve
      modulation of autonomic outflow in both the central and peripheral nervous
      systems as well as direct effects on the myocardium and vasculature. Although
      several lines of evidence indicate that the cardiovascular depressive effects of
      cannabinoids are mediated by peripherally localized CB1 receptors, recent studies
      provide strong support for the existence of as-yet-undefined endothelial and
      cardiac receptor(s) that mediate certain endocannabinoid-induced cardiovascular
      effects. The endogenous cannabinoid system has been recently implicated in the
      mechanism of hypotension associated with hemorrhagic, endotoxic, and cardiogenic
      shock, and advanced liver cirrhosis. Furthermore, cannabinoids have been
      considered as novel antihypertensive agents. A protective role of
      endocannabinoids in myocardial ischemia has also been documented. In this
      chapter, we summarize current information on the cardiovascular effects of
      cannabinoids and highlight the importance of these effects in a variety of
      pathophysiological conditions.

PMID- 16596793
TI  - Cannabinoid tolerance and dependence.
AB  - The use of marijuana for recreational and medicinal purposes has resulted in a
      large prevalence of chronic marijuana users. Consequences of chronic cannabinoid
      administration include profound behavioral tolerance and withdrawal symptoms upon
      drug cessation. A marijuana withdrawal syndrome is only recently gaining
      acceptance as being clinically significant. Similarly, laboratory animals exhibit
      both tolerance and dependence following chronic administration of cannabinoids.
      These animal models are being used to evaluate the high degree of plasticity that
      occurs at the molecular level in various brain regions following chronic
      cannabinoid exposure. In this review, we describe recent advances that have
      increased our understanding of the impact of chronic cannabinoid administration
      on cannabinoid receptors and their signal transduction pathways. Additionally, we
      discuss several potential pharmacotherapies that have been examined to treat
      marijuana dependence.

PMID- 16596794
TI  - Human studies of cannabinoids and medicinal cannabis.
AB  - Cannabis has been known as a medicine for several thousand years across many
      cultures. It reached a position of prominence within Western medicine in the
      nineteenth century but became mired in disrepute and legal controls early in the
      twentieth century. Despite unremitting world-wide suppression, recreational
      cannabis exploded into popular culture in the 1960s and has remained easily
      obtainable on the black market in most countries ever since. This ready
      availability has allowed many thousands of patients to rediscover the apparent
      power of the drug to alleviate symptoms of some of the most cruel and refractory
      diseases known to humankind. Pioneering clinical research in the last quarter of
      the twentieth century has given some support to these anecdotal reports, but the
      methodological challenges to human research involving a pariah drug are
      formidable. Studies have tended to be small, imperfectly controlled, and have
      often incorporated unsatisfactory synthetic cannabinoid analogues or smoked
      herbal material of uncertain composition and irregular bioavailability. As a
      result, the scientific evaluation of medicinal cannabis in humans is still in its
      infancy. New possibilities in human research have been opened up by the discovery
      of the endocannabinoid system, a rapidly expanding knowledge of cannabinoid
      pharmacology, and a more sympathetic political environment in several countries.
      More and more scientists and clinicians are becoming interested in exploring the
      potential of cannabis-based medicines. Future targets will extend beyond symptom
      relief into disease modification, and already cannabinoids seem to offer
      particular promise in the treatment of certain inflammatory and neurodegenerative
      conditions. This chapter will begin with an outline of the development and
      current status of legal controls pertaining to cannabis, following which the
      existing human research will be reviewed. Some key safety issues will then be
      considered, and the chapter will conclude with some suggestions as to future
      directions for human research.

PMID- 16596795
TI  - The pathogenesis of atherosclerosis.
AB  - Worldwide, more people die of the complications of atherosclerosis than of any
      other cause. It is not surprising, therefore, that enormous resources have been
      devoted to studying the pathogenesis of this condition. This article attempts to
      summarize present knowledge on the events that take place within the arterial
      wall during atherogenesis. Classical risk factors are not dealt with as they are
      the subjects of other parts of this book. First, we deal with the role of
      endothelial dysfunction and infection in initiating the atherosclerotic lesion.
      Then we describe the development of the lesion itself, with particular emphasis
      on the cell types involved and the interactions between them. The next section of
      the chapter deals with the events leading to thrombotic occlusion of the
      atherosclerotic vessel, the cause of heart attack and stroke. Finally, we
      describe the advantages--and limitations--of current animal models as they
      contribute to our understanding of atherosclerosis and its complications.

PMID- 16596796
TI  - Risk factors for atherosclerotic vascular disease.
AB  - Several controlled interventional trials have shown the benefit of anti
      hypertensive and hypolipidaemic drugs for the prevention of coronary heart
      disease (CHD). International guidelines for the prevention of CHD agree in their
      recommendations for tertiary prevention and recommend lowering the blood pressure
      to below 140 mm/90 mm Hg and low density lipoprotein (LDL)-cholesterol to below
      2.6 mmol/l in patients with manifest CHD. Novel recommendations for secondary
      prevention are focused on the treatment of the pre-symptomatic high-risk patient
      with an estimated CHD morbidity risk of higher than 20% per 10 years or an
      estimated CHD mortality risk of higher than 5% per 10 years. For the calculation
      of this risk, the physician must record the following risk factors: sex, age,
      family history of premature myocardial infarction, smoking, diabetes, blood
      pressure, total cholesterol, LDL-cholesterol, high-density lipoprotein (HDL)
      cholesterol, and triglyceride. This information allows the absolute risk of
      myocardial infarction to be computed by using scores or algorithms which have
      been deduced from results of epidemiological studies. To improve risk prediction
      and to identify new targets for intervention, novel risk factors are sought. High
      plasma levels of C-reactive protein has been shown to improve the prognostic
      value of global risk estimates obtained by the combination of conventional risk
      factors and may influence treatment decisions in patients with intermediate
      global cardiovascular risk (CHD morbidity risk of 10%-20% per 10 years or CHD
      mortality risk of 2%-5% per 10 years).

PMID- 16596797
TI  - Metabolic syndrome: therapeutic considerations.
AB  - The metabolic syndrome is a constellation of metabolic risk factors for
      atherosclerotic cardiovascular disease (ASCVD) occurring in one individual. There
      are five cardiovascular risk factors that accompany the metabolic syndrome:
      atherogenic dyslipidemia [elevated apolipoprotein B (apo B), elevated
      triglyceride, small low-density lipoprotein (LDL) particles, and low high-density
      lipoprotein (HDL)cholesterol], elevated blood pressure, elevated glucose, a
      prothrombotic state, and a proinflammatory state. The likelihood of an individual
      developing metabolic syndrome is enhance by underlying risk factors, notably,
      obesity, insulin resistance, lack of physical activity, advancing age, and
      hormonal factors (e.g., androgens and corticosteroids). Besides being at higher
      risk for ASCVD, persons with the metabolic syndrome are at increased risk for
      type 2 diabetes. Persons with the metabolic syndrome deserve management in the
      clinical setting to reduce the risk for both ASCVD and type 2 diabetes. The two
      major therapeutic strategies for treatment of affected persons are modification
      of the underlying risk factors and separate drug treatment of the particular
      metabolic risk factors when appropriate. First-line therapy for underlying risk
      factors is therapeutic lifestyle changes, i.e., weight loss in obese persons,
      increased physical activity, and anti-atherogenic diet. These changes will
      improve all of the metabolic risk factors. Whether use of drugs to reduce insulin
      resistance is effective, safe, and cost-effective before the onset of diabetes
      awaits the results of more clinical research. Turning to individual risk
      components, for atherogenic dyslipidemia, drug therapies that promote lowering of
      apo B and raise HDL cholesterol will be needed for higher risk patients.
      Treatment of categorical hypertension with drugs has become standard practice.
      When hyperglycemia reaches the diabetic level, glucose-lowering agents will
      become necessary when dietary control is no longer effective, and reduction of a
      prothrombotic state with low-dose aspirin may be indicated in higher-risk
      patients.

PMID- 16596798
TI  - Physical activity, obesity and cardiovascular diseases.
AB  - Sedentary lifestyle and overweight are major public health, clinical, and
      economical problems in modern societies. The worldwide epidemic of excess weight
      is due to imbalance between physical activity and dietary energy intake.
      Sedentary lifestyle, unhealthy diet, and consequent overweight and obesity
      markedly increase the risk of cardiovascular diseases. Regular physical activity
      45-60 min per day prevents unhealthy weight gain and obesity, whereas sedentary
      behaviors such as watching television promote them. Regular exercise can markedly
      reduce body weight and fat mass without dietary caloric restriction in overweight
      individuals. An increase in total energy expenditure appears to be the most
      important determinant of successful exercise-induced weight loss. The best long
      term results may be achieved when physical activity produces an energy
      expenditure of at least 2,500 kcal/week. Yet, the optimal approach in weight
      reduction programs appears to be a combination of regular physical activity and
      caloric restriction. A minimum of 60 min, but most likely 80-90 min of moderate
      intensity physical activity per day may be needed to avoid or limit weight regain
      in formerly overweight or obese individuals. Regular moderate intensity physical
      activity, a healthy diet, and avoiding unhealthy weight gain are effective and
      safe ways to prevent and treat cardiovascular diseases and to reduce premature
      mortality in all population groups. Although the efforts to promote
      cardiovascular health concern the whole population, particular attention should
      be paid to individuals who are physically inactive, have unhealthy diets or are
      prone to weight gain. They have the highest risk for worsening of the
      cardiovascular risk factor profile and for cardiovascular disease. To combat the
      epidemic of overweight and to improve cardiovascular health at a population
      level, it is important to develop strategies to increase habitual physical
      activity and to prevent overweight and obesity in collaboration with communities,
      families, schools, work sites, health care professionals, media and policymakers.

PMID- 16596800
TI  - Dietary cholesterol, atherosclerosis and coronary heart disease.
AB  - As early as at the beginning of the last century, animal studies have pointed to
      a causal role of dietary cholesterol in atherogenesis. In humans, however, most
      observational studies have not provided convincing evidence for an impact of
      cholesterol intake on coronary heart disease (CHD). Rather, these studies have
      consistently established a close association between a certain eating pattern and
      the risk of CHD. This eating pattern has usually been characterized by a high
      intake of total fat, saturated fatty acids (SFA) and cholesterol, and a low
      intake of fiber and polyunsaturated fatty acids (PUFA). In typical western diets
      the amounts of total fat, SFA, and cholesterol are strongly correlated with each
      other, while they are negatively related to the intake of fiber and PUFA. Thus,
      it has not been possible to determine whether the association between the above
      mentioned eating pattern and CHD is due to the high consumption of SFA,
      cholesterol, both, or an insufficient supply of one or more protective factors
      such as fiber or PUFA. As the consumption of eggs leads to a high intake of
      cholesterol without necessarily resulting in high uptake levels of SFA and total
      fat, several groups have tried to elucidate the effect of cholesterol by
      investigating the relationship between the consumption of eggs and the
      development of CHD. Based on these studies, the association between dietary
      cholesterol and CHD risk is, if anything, minor in nature. This is consistent
      with the finding that an increase in dietary cholesterol intake results in only a
      minimal increase in the total/high-density lipoprotein cholesterol ratio. Taken
      together these studies suggest that the association between dietary cholesterol
      and CHD is small, as most subjects can effectively adapt to higher levels of
      cholesterol intake. Nevertheless, lowering dietary cholesterol content might
      reduce the risk of CHD considerably in a subgroup of individuals who are highly
      responsive to changes in cholesterol intake.

PMID- 16596799
TI  - Fatty acids and atherosclerotic risk.
AB  - Most research concerning the effects of dietary fatty acids on atherosclerotic
      risk has focused on their effects on lipid and lipoprotein metabolism. However,
      it is known that fatty acids also influence a number of other relevant mechanisms
      involved in atherosclerosis such as lipid peroxidation, inflammation and
      haemostasis. The most favourable distribution of cholesterol over the various
      lipoproteins is achieved when saturated and trans fatty acids are replaced by a
      mixture of cis-unsaturated fatty acids. Furthermore, fatty acids from fish oil
      lower triacylglycerol concentrations. Effects on other atherosclerotic risk
      markers are less evident. Monounsaturated fatty acids maybe preferable above
      other fatty acids with respect to low-density lipoprotein oxidation as measured
      by indirect in vitro assays. The relevance of these assays for the in vivo
      situation is, however, limited. With respect to inflammation, mainly the effects
      of n-3 polyunsaturated fatty acids from fish oil have been studied, but results
      were inconsistent. Also results from studies evaluating the effects of fatty
      acids on haemostatic risk markers were inconsistent, which may be partly related
      to the use of different analytical methods. The most consistent finding however
      is the potential beneficial effect of moderate intakes of fish oil on platelet
      aggregation. Furthermore, reducing total fat intake rather than changing the
      fatty acid composition of the diet may beneficially affect the coagulation
      system. In conclusion, while beneficial effects on atherosclerotic risk are
      mainly ascribed to cis-unsaturated fatty acids, it remains debateable whether
      trans and saturated fatty acids in the diet have to be replaced by cis
      unsaturated fatty acids or by carbohydrates. To answer this question adequately
      more validated methods are needed that reflect in vivo lipid peroxidation,
      inflammation and haemostasis.

PMID- 16596801
TI  - Plant sterols and stanols.
AB  - The expanding market of 'functional foods' containing plant sterols and stanols
      has focused interest on their cholesterol-lowering effects as well on possible
      adverse effects. Trials of cholesterol lowering demonstrate that intake of 2
      g/day of plant sterols and stanols reduces serum low-density lipoprotein (LDL)
      cholesterol concentrations by approximately 10%. Safety concerns regarding
      elevations in serum plant sterol levels, or effects on fat-soluble vitamin
      absorption or hypothetical effects on serum sex hormone balance have received
      attention and been addressed in studies. Plant sterol (but not stanol)
      supplementation increased serum plant sterol concentrations but these levels
      remained much lower than those observed in homozygous sitosterolemia making an
      adverse health effect unlikely. Prolonged statin therapy also causes elevations
      in all cholesterol-adjusted plant sterol levels as well as small but significant
      elevations in serum unadjusted campesterol levels from baseline. This is probably
      caused by a statin-induced reduction in biliary cholesterol efflux resulting in a
      diminished intestinal cholesterol pool. The diminished competition with
      cholesterol molecules allows more plant sterol molecules to become incorporated
      in mixed micelles facilitating their uptake in enterocytes. With the exception of
      beta-carotene, reductions in serum concentrations of fat-soluble (pro)vitamins
      are usually abolished by adjustment for cholesterol suggesting that they reflect
      reductions in carrier lipoproteins, mainly LDL. The small reductions in serum
      beta-carotene are not regarded as a major concern, nor have any adverse effects
      on sex hormone metabolism been demonstrated apart from parenteral administration
      of large doses in experimental animals. However, as increasing consumer
      populations become exposed to a large variety of food products enriched with
      plant sterols and stanols the likelihood of rare adverse effects increases and
      surveillance is necessary.

PMID- 16596803
TI  - Dietary antioxidants and paraoxonases against LDL oxidation and atherosclerosis
      development.
AB  - Oxidative modification of low-density lipoprotein (LDL) in the arterial wall
      plays a key role in the pathogenesis of atherosclerosis. Under oxidative stress
      LDL is exposed to oxidative modifications by arterial wall cells including
      macrophages. Oxidative stress also induces cellular-lipid peroxidation, resulting
      in the formation of 'oxidized macrophages', which demonstrate increased capacity
      to oxidize LDL and increased uptake of oxidized LDL. Macrophage-mediated
      oxidation of LDL depends on the balance between pro-oxidants and antioxidants in
      the lipoprotein and in the cells. LDL is protected from oxidation by
      antioxidants, as well as by a second line of defense--paraoxonase 1 (PON1), which
      is a high-density lipoprotein-associated esterase that can hydrolyze and reduce
      lipid peroxides in lipoproteins and in arterial cells. Cellular paraoxonases
      (PON2 and PON3) may also play an important protective role against oxidative
      stress at the cellular level. Many epidemiological studies have indicated a
      protective role for a diet rich in fruits and vegetables against the development
      and progression of cardiovascular disease. A large number of studies provide data
      suggesting that consumption of dietary antioxidants is associated with reduced
      risk for cardiovascular diseases. Basic research provides plausible mechanisms by
      which dietary antioxidants might reduce the development of atherosclerosis. These
      mechanisms include inhibition of LDL oxidation, inhibition of cellular lipid
      peroxidation and consequently attenuation of cell-mediated oxidation of LDL. An
      additional possible mechanism is preservation/increment of paraoxonases activity
      by dietary antioxidants. This review chapter presents recent data on the anti
      atherosclerotic effects and mechanism of action of three major groups of dietary
      antioxidants-vitamin E, carotenoids and polyphenolic flavonoids.

PMID- 16596802
TI  - Carbohydrates and dietary fiber.
AB  - The most widely spread eating habit is characterized by a reduced intake of
      dietary fiber, an increased intake of simple sugars, a high intake of refined
      grain products, an altered fat composition of the diet, and a dietary pattern
      characterized by a high glycemic load, an increased body weight and reduced
      physical activity. In this chapter the effects of this eating pattern on disease
      risk will be outlined. There are no epidemiological studies showing that the
      increase of glucose, fructose or sucrose intake is directly and independently
      associated with an increased risk of atherosclerosis or coronary heart disease
      (CHD). On the other hand a large number of studies has reported a reduction of
      fatal and non-fatal CHD events as a function of the intake of complex
      carbohydrates--respectively 'dietary fiber' or selected fiber-rich food (e.g.,
      whole grain cereals). It seems that eating too much 'fast' carbohydrate [i.e.,
      carbohydrates with a high glycemic index (GI)] may have deleterious long-term
      consequences. Indeed the last decades have shown that a low fat (and
      consecutively high carbohydrate) diet alone is not the best strategy to combat
      modern diseases including atherosclerosis. Quantity and quality issues in
      carbohydrate nutrient content are as important as they are for fat. Multiple
      lines of evidence suggest that for cardiovascular disease prevention a high sugar
      intake should be avoided. There is growing evidence of the high impact of dietary
      fiber and foods with a low GI on single risk factors (e.g., lipid pattern,
      diabetes, inflammation, endothelial function etc.) as well as also the
      development of the endpoints of atherosclerosis especially CHD.

PMID- 16596804
TI  - Soy, isoflavones and atherosclerosis.
AB  - Consumption of soy protein is associated with a lower risk of cardiovascular
      disease in man, and reduced atherosclerosis in a variety of experimental animals.
      Although a portion of the cardiovascular protective effects appears to be due to
      reductions in plasma lipoprotein concentration, in most people the magnitude of
      this effect is relatively small. In many, but not all studies using animal
      models, the reduction in atherosclerosis is in part independent of changes in
      plasma lipids and lipoproteins. This implies that there may be a direct effect on
      the arterial wall of one or more of the components in soyprotein that reduces
      susceptibility to atherosclerosis. The most actively studied components of soy
      protein that may be responsible for these anti-atherogenic effects are the
      isoflavones and various protein factions. Extraction of isoflavones and other
      alcohol-soluble components from soy protein lowers, but does not eliminate its
      ability to reduce atherosclerosis. Surprisingly, in most studies, adding back the
      isoflavone-rich alcohol extract to the previously extracted soy protein, or to
      another protein, does not restore its lipoprotein lowering or anti-atherogenic
      properties. This implies that alcohol extraction either destroys an active
      component of soy, alters the structural integrity of the soy proteins, or
      disassociates a required isoflavone-soy protein complex. Understanding the
      mechanism of this effect is an important goal for future research. Likewise, the
      sites of action on the arterial wall, and the mechanisms by which various soy
      components act to reduce atherosclerosis are just now being studied. The recent
      demonstration that expression of estrogen receptor alpha is required for
      atheroprotection by soy protein provides important new mechanistic insight. Other
      properties of soy, including antioxidant, anti-inflammatory and potentially
      antithrombogenic properties need to be explored more mechanistically before the
      full potential of dietary soy protein for the protection from cardiovascular
      disease will be known.

PMID- 16596805
TI  - Homocysteine and B vitamins.
AB  - Homocysteine (tHcy) is an intermediate sulfur-containing amino acid which acts as
      a methyl group donor for methionine metabolism. Increased serum concentrations
      (=hyperhomocysteinemia, >10 micromol/l) have been associated with an increased
      cardiovascular risk. Homocystinuria, an infrequent genetic disease usually due to
      lack of cystathione beta-synthase, has been found with severely elevated serum
      homocysteine values (>150 micromol/l). Functional gene polymorphisms of key
      enzymes (e.g., N5,N10-methylene-tetrahydrofolate reductase) and dietary B-vitamin
      deficiencies in the elderly are, however, frequent in the 'Western' population.
      Hyperhomocysteinemia has been associated with other vascular effects such as
      atherothrombosis and endothelial dysfunction due to its auto-oxidative potential,
      thereby increasing the production of reactive oxygen species. Other effects may
      involve neurodegenerative diseases such as Alzheimer or dementia praecox of the
      elderly. Therapeutic interventions lowering tHcy may therefore offer novel tools
      for the prevention and treatment of atherosclerosis. B-vitamin supplementation
      (folic acid=vitamin B9, vitamin B6 and vitamin B12) is an efficient and safe tHcy
      lowering therapy, decreases tHcy by 30%-50% and has been shown to lower
      cardiovascular morbidity and mortality. Furthermore, folic acid supplementation
      has been shown to reduce or even almost eliminate neurotubular birth defects
      (spina bifida) and to markedly decrease the rate of megaloblastic anemia. Thus,
      fortification of flour with folic acid in the USA was advocated several years ago
      in order to prevent these entities.

PMID- 16596806
TI  - Alcohol.
AB  - Alcohol consumption affects overall mortality. Light to moderate alcohol
      consumption reduces the risk of coronary heart disease; epidemiological,
      physiological and genetic data show a causal relationship. Light to moderate
      drinking is also associated with a reduced risk of other vascular diseases and
      probably of type 2 diabetes. Mortality and disease risk increase at higher levels
      of alcohol consumption. A substantial portion of the benefit of moderate drinking
      is connected with the alcohol component. However, small differences in effects of
      various alcoholic beverages on minor risk factors may occur. Proposed protective
      mechanisms include improved vascular elasticity, anti-thrombotic and anti
      inflammatory processes and most importantly, the stimulation of high-density
      lipoprotein-mediated processes such as reverse cholesterol transport and
      antioxidative effects.

PMID- 16596807
TI  - Lipid and non-lipid effects of statins.
AB  - Long- and short-term trials with the 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (statins) have demonstrated significant reductions in
      cardiovascular events in patients with and without history of coronary heart
      disease. Statins are well-established low-density lipoprotein (LDL)-lowering
      agents, but their clinical benefit is believed to result from a number of lipid
      and non-lipid effects beyond LDL lowering, including a rise in plasma high
      density lipoprotein levels. Beyond improving the lipid profile, statins have
      additional non-lipid effects including benefit on endothelial function,
      inflammatory mediators, intima-media thickening, prothombotic factors that
      ultimately result in plaque stabilization. These effects arise through the
      inhibition of several mevalonate-derived metabolites other than cholesterol
      itself, which are involved in the control of different cellular functions.
      Although statins represent the gold standard in the prevention and treatment of
      coronary heart disease, combination therapy with other lipid-lowering drugs, as
      well as novel therapeutic indications, may increase their therapeutic potential.

PMID- 16596808
TI  - Fibrates.
AB  - Atherosclerosis of the large arteries is the main origin of cerebro- and
      cardiovascular diseases, the leading causes of mortality and morbidity in
      industrialized countries. The pathophysiology of coronary and cerebrovascular
      atherosclerosis is multifactorial and complex. Fibrates are hypolipidemic drugs
      that lower progression of atherosclerotic lesions mainly through activation of
      the nuclear receptor peroxisome-proliferator activated receptor-alpha. In
      addition, fibrates exert pleiotropic and anti-inflammatory actions. In this
      chapter, we will focus on the different effects of fibrates impacting on the
      development of atherosclerosis.

PMID- 16596809
TI  - ACE inhibitors and angiotensin II receptor antagonists.
AB  - The biological actions of angiotensin II (ANG), the most prominent hormone of the
      renin-angiotensin-aldosterone system (RAAS), may promote the development of
      atherosclerosis in many ways. ANG aggravates hypertension, metabolic syndrome,
      and endothelial dysfunction, and thereby constitutes a major risk factor for
      cardiovascular disease. The formation of atherosclerotic lesions involves local
      uptake, synthesis and oxidation of lipids, inflammation, as well as cellular
      migration and proliferation--mechanisms that may all be enhanced by ANG via its
      AT1 receptor. ANG may also increase the risk of acute thrombosis by destabilizing
      atherosclerotic plaques and enhancing the activity of thrombocytes and
      coagulation. After myocardial infarction, ANG promotes myocardial remodeling and
      fibrosis, and its many pathological mechanisms deteriorate the prognosis of these
      high-risk patients in particular. Therapeutically, inhibitors of the angiotensin
      I-converting enzyme (ACEI) and AT1 receptor blockers (ARB) are available to
      suppress the generation and cellular signaling of ANG, respectively. Despite
      major differences in the efficacy of ANG suppression and the modulation of other
      hormones and receptors, both classes of drugs are generally effective in
      attenuating numerous pathomechanisms of ANG in vitro, and in diminishing the
      development of atherosclerotic lesions and restenosis after angioplasty in
      various animal models. In clinical therapy, ACEI and ACE are well-tolerated
      antihypertensive drugs that also improve the prognosis of heart failure patients.
      After myocardial infarction and in stable coronary heart disease, ACEI have been
      shown to reduce mortality in a manner independent of hemodynamic alterations.
      However, there is little evidence that inhibitors of the RAAS may be effective
      against arterial restenosis, and a possible benefit of these substances compared
      to other antihypertensive drugs in the primary prevention of coronary heart
      disease in hypertensive patients is still a matter of debate, possibly depending
      on the specific substance and condition being investigated. As such, the general
      clinical efficacy of ACEI and ARB may be due to a positive influence on
      hemodynamic load, vascular function, myocardial remodeling, and neuro-humoral
      regulation, rather than to a direct attenuation of the atherosclerotic process.
      Further therapeutic advances may be achieved by identifying optimum drugs,
      patient populations, and treatment protocols.

PMID- 16596810
TI  - Inhibition of platelet activation and aggregation.
AB  - It has recently been established that platelets are involved at all stages of
      atherosclerotic disease. A major platelet mediated process is the acute vessel
      closure at the site of atherosclerotic plaque rupture and there is emerging
      evidence for platelet adhesion to endothelial cells in the early stage of
      atherosclerotic disease. This, through engagement of other cells, leads to the
      development of the atherosclerotic plaque. Beside dietary, cholesterol- and lipid
      lowering, and other pharmaceutical approaches antiplatelet therapy plays an
      important part in the treatment of atherosclerosis and its multifarious clinical
      manifestations. Antiplatelet therapy and the currently approved substances for
      oral (acetylsalicylic acid, dipyridamole, cilostazol, ticlopidin and clopidogrel)
      and parenteral (acetylsalicylic acid, abciximab, eptifibatide and tirofiban)
      administration are discussed in the following section. Attention is given to each
      single agent and its mechanism of action. Differences in pharmacodynamic and
      pharmacokinetic properties are elucidated and outlook on future antiplatelet
      strategies is discussed.

PMID- 16596811
TI  - The ABC of hepatic and intestinal cholesterol transport.
AB  - The liver and (small) intestine are key organs in maintenance of cholesterol
      homeostasis: both organs show active de novo cholesterogenesis and are able to
      transport impressive amounts of newly synthesized and diet-derived cholesterol
      via a number of distinct pathways. Cholesterol trafficking involves the concerted
      action of a number of transporter proteins, some of which have been identified
      only recently. In particular, several ATP-binding cassette (ABC) transporters
      fulfil critical roles. For instance, the ABCG5/ABCG8 couple is crucial for
      hepatobiliary and intestinal cholesterol excretion, while ABCA1 is essential for
      high-density lipoprotein formation and, hence, for inter-organ trafficking of the
      highly water-insoluble cholesterol molecules. Very recently, the Niemann-Pick C1
      like 1 protein has been identified as a key player in cholesterol absorption by
      the small intestine and may represent a target of the cholesterol absorption
      inhibitor ezetimibe. Alterations in hepatic and intestinal cholesterol transport
      affect circulating levels of atherogenic lipoproteins and thus the risk for
      cardiovascular disease. This review specifically deals with the processes of
      hepatobiliary cholesterol excretion and intestinal cholesterol absorption as well
      as the interactions between these important transport routes. During the last few
      years, insight into the mechanisms of hepatic and intestinal cholesterol
      transport has greatly increased not in the least by the identification of
      involved transporter proteins and the (partial) elucidation of their mode of
      action. In addition, information has become available on (transcription) factors
      regulating expression of the encoding genes. This knowledge is of great
      importance for the development of a tailored design of novel plasma cholesterol
      lowering strategies.

PMID- 16596812
TI  - Inhibition of the synthesis of apolipoprotein B-containing lipoproteins.
AB  - Increased serum concentrations of low density lipoproteins represent a major
      cardiovascular risk factor. Low-density lipoproteins are derived from very low
      density lipoproteins secreted by the liver. Apolipoprotein (apo)B that
      constitutes the essential structural protein of these lipoproteins exists in two
      forms, the full length form apoB-100 and the carboxy-terminal truncated apoB-48.
      The generation of apoB-48 is due to editing of the apoB mRNA which generates a
      premature stop translation codon. The editing of apoB mRNA is an important
      regulatory event because apoB-48-containing lipoproteins cannot be converted into
      the atherogenic low density lipoproteins. The apoB gene is constitutively
      expressed in liver and intestine, and the rate of apoB secretion is regulated
      post-transcriptionally. The translocation of apoB into the endoplasmic reticulum
      is complicated by the hydrophobicity of the nascent polypeptide. The assembly and
      secretion of apoB-containing lipoproteins within the endoplasmic reticulum is
      strictly dependent on the microsomal tricylceride transfer protein which shuttles
      triglycerides onto the nascent lipoprotein particle. The overall synthesis of
      apoB lipoproteins is regulated by proteosomal and nonproteosomal degradation and
      is dependent on triglyceride availability. Noninsulin dependent diabetes
      mellitus, obesity and the metabolic syndrome are characterized by an increased
      hepatic synthesis of apoB-containing lipoproteins. Interventions aimed to reduce
      the hepatic secretion of apoB-containing lipoproteins are therefore of great
      clinical importance. Lead targets in these pathways are discussed.

PMID- 16596813
TI  - Therapy of hyper-Lp(a).
AB  - Lipoprotein (a) [Lp(a)] appears to be one of the most atherogenic lipoproteins.
      It consists of a low-density lipoprotein (LDL) core in addition to a covalently
      bound glycoprotein, apolipoprotein (a) [apo(a)]. Apo(a) exists in numerous
      polymorphic forms. The size polymorphism is mediated by the variable number of
      kringle-4 Type-II repeats found in apo(a). Plasma Lp(a) levels are determined to
      more than 90% by genetic factors. Plasma Lp(a) levels in healthy individuals
      correlate significantly high with apo(a) biosynthesis and not with its
      catabolism. There are several hormones known to have a strong impact on Lp(a)
      metabolism. In certain diseases, such as kidney disease, Lp(a) catabolism is
      impaired leading to up to fivefold elevations. Lp(a) levels rise with age but are
      otherwise influenced only little by diet and lifestyle. There is no safe and
      efficient way of treating individuals with elevated plasma Lp(a) concentrations.
      Most of the lipid-lowering drugs have either no significant influence on Lp(a) or
      exhibit a variable effect in patients with different forms of primary and
      secondary hyperlipoproteinemia. There is without doubt a strong need to
      concentrate on the development of specific medications to selectively target
      Lp(a) biosynthesis, Lp(a) assembly and Lp(a) catabolism. So far only anabolic
      steroids were found to drastically reduce Lp(a) plasma levels. This class of
      substance cannot, of course, be used for treatment of patients with hyper-Lp(a).
      We recommend that the mechanism of action of these drugs be studied in more
      detail and that the possibility of synthesizing derivatives which may have a more
      specific effect on Lp(a) without having any side effects be pursued. Other
      strategies that may be of use in the development of drugs for treatment of
      patients with hyper-Lp(a) are discussed in this review.

PMID- 16596814
TI  - Modulation of high-density lipoprotein cholesterol metabolism and reverse
      cholesterol transport.
AB  - Low high-density lipoprotein (HDL)-cholesterol (C) is an important risk factor
      for coronary heart disease. In vitro, HDL exerts several potentially anti
      atherogenic effects including reverse cholesterol transport (RCT) from peripheral
      cells to the liver. Hence, raising HDL-C has become an interesting target for
      anti-atherosclerotic drug therapy. Levels of HDL-C and the composition of HDL
      subclasses in plasma are regulated by apolipoproteins, lipolytic enzymes, lipid
      transfer proteins, receptors, and cellular transporters. The interplay of these
      factors leads to RCT and determines the composition and thereby the anti
      atherogenic properties of HDL. Recent findings suggest that the mechanism of HDL
      modification rather than a sole increase in HDL-C determines the efficacy of anti
      atherosclerotic drug therapy. In several controlled and prospective intervention
      studies, patients with low HDL-C and additional risk factors benefited from
      treatment with fibrates or statins. However, in only some of the fibrate trials
      was prevention of coronary events in patients with low HDL-C and
      hypertriglyceridaemia related to an increase in HDL-C. This may be because
      currently available drugs increase HDL-C levels only moderately and because HDL
      levels per se do not necessarily correlate with the functionality of HDL.
      However, several novel targets to modify RCT have emerged from the recent
      understanding of HDL synthesis, maturation and catabolism. The four major targets
      for an anti-atherogenic strategy in HDL metabolism include stimulation of apoA-I
      synthesis and secretion, the stimulation of ABCA1 expression, the inhibition of
      cholesterol ester transfer protein, and the up-regulation of scavenger receptor
      BI. These and other modulations of HDL metabolism are thought to result in
      improved RCT making them attractive targets for the development of new regimens
      of anti-atherogenic drug therapy.

PMID- 16596815
TI  - Inhibition of lipoprotein lipid oxidation.
AB  - According to the oxidative modification hypothesis, antioxidants that inhibit the
      oxidation of low-density lipoprotein (LDL) are expected to attenuate
      atherosclerosis, yet not all antioxidants that inhibit LDL oxidation in vitro
      inhibit disease in animal models of atherosclerosis. As with animal studies, a
      benefit with dietary supplements of antioxidants in general and vitamin E in
      particular was anticipated in humans, yet the overall outcome of large,
      randomized controlled studies has been disappointing. However, in recent years it
      has become clear that the role of vitamin E in LDL oxidation and the relationship
      between in vitro and in vivo inhibition of LDL oxidation are more complex than
      previously appreciated, and that oxidative events in addition to LDL oxidation in
      the extracellular space need to be considered in the context of an antioxidant as
      a therapeutic drug against atherosclerosis. This review focuses on some of these
      complexities, proposes a novel method to assess in vitro 'oxidizability' of
      lipoprotein lipids, and summarizes the present situation of development of
      antioxidant compounds as drugs against atherosclerosis and related cardiovascular
      disorders.

PMID- 16596816
TI  - Correction of insulin resistance and the metabolic syndrome.
AB  - Insulin resistance is a common phenomenon of the metabolic syndrome, which is
      clinically characterized by a clustering of various cardiovascular risk factors
      in a single individual and a higher prevalence of respective complications, such
      as coronary heart disease and stroke. At the cellular level, insulin resistance
      is defined as a reduced insulin action, which can affect not only glucose uptake,
      but also gene regulation. Elucidation of novel signaling networks within the cell
      which are mediating and affecting insulin action will reveal many new genes and
      drug targets that are potentially of clinical relevance in the future. In this
      chapter, we propose that the metabolic syndrome might be a clinical consequence
      of altered gene regulation. This is illuminated in the context of transcription
      factors, e.g., sterol regulatory element binding proteins (SREBPs), coupling
      signals from nutrients, metabolites, and hormones at the gene regulatory level
      with pathobiochemical features of increased lipid accumulation in lean nonadipose
      tissues. The phenomenon of ectopic lipid accumulation (lipotoxicity) appears to
      be a novel link between insulin resistance, obesity, and possibly other features
      of the metabolic syndrome. Therefore, the investigation of specific gene
      regulatory networks and their alterations might be a clue to understanding the
      development and clustering of different cardiovascular risk factors in different
      individuals. As cellular sensors transcription factors--as common denominators of
      gene regulatory networks--might thereby also determine the susceptibility of
      individuals to cardiovascular risk factors and their complications.

PMID- 16596817
TI  - Protection of endothelial function.
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-monophosphat
      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
      nor- mal function of the vascular endothelium. Endothelin acts as the natural
      counterpart to endothelium-derived NO. In man, besides its effect of increasing
      arterial blood pressure, ET-1 induces vascular and myocardial hypertrophy, which
      are independent risk factors for cardiovascular morbidity and mortality. Current
      therapeutic strategies concentrate mainly on lowering of 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.
      Novel therapeutic strategies specifically targeting inflammation thus bear great
      potential for the prevention and treatment of atherosclerotic vascular disease.

PMID- 16596818
TI  - Modulation of smooth muscle cell proliferation and migration: role of smooth
      muscle cell heterogeneity.
AB  - Proliferation and migration of smooth muscle cells (SMCs) from the media towards
      the intima are key events in atherosclerosis and restenosis. During these
      processes, SMC undergo phenotypic modulations leading to SMC dedifferentiation.
      The identification and characterization of factors controlling these phenotypic
      changes are crucial in order to prevent the formation of intimal thickening. One
      of the questions which presently remains open, is to know whether any SMCs of the
      media are capable of accumulating into the intima or whether only a predisposed
      medial SMC subpopulation is involved in this process. The latter hypothesis
      implies that arterial SMCs are phenotypically heterogenous. In this chapter, we
      will describe the distinct SMC phenotypes identified in arteries of various
      species, including humans. Their role in the formation of intimal thickening will
      be discussed.

PMID- 16596819
TI  - Modulation of macrophage function and metabolism.
AB  - Several drugs or pharmacologically active molecules such as statins, calcium
      antagonists, and PPAR agonists have been shown to affect macrophage functions
      that contribute to atherosclerosis and modulate plaque stability. For example,
      the modulation of matrix metalloproteinase secretion and cholesterol metabolism
      in macrophages may help to prevent cardiovascular disease independently of the
      correction of risk factors.

PMID- 16596820
TI  - Inflammation is a crucial feature of atherosclerosis and a potential target to
      reduce cardiovascular events.
AB  - Contrary to popular opinion, atherosclerosis is not a disease unique to modern
      civilization. In fact, atherosclerotic lesions have been found in the arteries of
      mummies dating back to 1,500 B.C., and yet our understanding of this complex
      process is still evolving. A fusion of basic science advances and clinical
      research findings has radically altered our traditional concepts about the
      pathogenesis and treatment of the clinical complications of atherosclerosis. Most
      physicians previously regarded the artery as a being merely a blood conduit that
      became encrusted with lipid detritus as part of the aging process. Modern-day
      treatment of atherosclerosis has arisen primarily from an understanding of the
      epidemiology of the disease rather than its pathophysiology, in that risk factors
      have traditionally been targeted. Our concepts of atherogenesis have evolved from
      vague ideas of inevitable degeneration to a much better defined scenario of
      molecular and cellular events. As we enhance our understanding of its fundamental
      mechanism, we can begin to approach atherogenesis as a modifiable rather than
      ineluctable process. Indeed, as we recognize now that inflammation plays a
      pivotal role in the process of atherosclerosis, it is noteworthy to evaluate the
      effect of modern therapies on this facet of the disease.

PMID- 16596821
TI  - Autoimmune mechanisms of atherosclerosis.
AB  - Accumulating evidence supports an autoimmune mechanism as one of the prime
      pathogenic processes involved in the development of atherosclerosis. So far,
      three proteins, including heat shock proteins (HSPs), oxidized low-density
      lipoprotein (oxLDL), and beta2 glycoprotein1 (beta2GP1) have been recognized as
      autoantigens. It has been demonstrated that risk factors for atherosclerosis,
      such as hypercholesterolemia, hypertension, infections, and oxidative stress,
      evoke increased expression of HSPs in cells of atherosclerotic lesions.
      Autoantibody levels against HSPs are significantly increased in patients with
      atherosclerosis and T lymphocytes specifically responding to these autoantigens
      have been demonstrated within atherosclerotic plaques. Subcutaneous immunization
      of animals with HSP65 induced atheroma formation in the arterial wall.
      Furthermore, circulating immunoglobulin (Ig) G and IgM oxidized low-density
      lipoprotein (oxLDL) antibodies are present in the plasma of animals and humans
      and form immune complexes with oxLDL in atherosclerotic lesions. These antibodies
      closely correlate with the progression and regression of atherosclerosis in
      murine models. Interestingly, recent reports demonstrated that pneumococcal
      vaccination to LDL receptor-deficient mice results in elevation of anti-oxLDL IgM
      Ab EO6, which is inversely correlated with the development of atherosclerosis.
      Finally, it has been observed that autoantigen beta2GP1 localizes in the atheroma
      and that autoantibodies to beta2GP1 are correlated with the incidence of
      atherosclerosis in patients. Hence, these autoimmune reactions to HSPs, oxLDL and
      beta2GP1 can contribute to the initiation and progression of atherosclerosis.

PMID- 16596822
TI  - Drug therapies to prevent coronary plaque rupture and erosion: present and
      future.
AB  - Patients at high risk for coronary heart disease usually have a number of
      atherosclerotic plaques in their coronary arteries. Some plaques grow inward and,
      once they have caused a critical degree of luminal stenosis, lead to chronic
      anginal symptoms. Other plaques grow outward and remain silent unless they
      disrupt and trigger an acute coronary event. Either type of plaque may become
      vulnerable to rupture or erosion once they have reached an advanced stage.
      Typically, a highly stenotic fibrotic plaque is prone to erosion, whereas an
      advanced lipid-rich thin-cap fibroatheroma is prone to rupture. Because of the
      multitude and complex nature of the coronary lesions and our inability to detect
      silent rupture-prone plaques, the best practical approach to prevent acute
      coronary events is to treat the vulnerable patient, i.e., to eliminate the risk
      factors of coronary disease. Despite such preventive measures, a sizable number
      of patients still experience acute coronary events due to plaque erosion or
      rupture. Thus, there is room for new avenues to pharmacologically stabilize
      vulnerable plaques. The development of new noninvasive tools to detect the
      progression and regression of individual non-stenotic rupture-prone plaques will
      allow testing of such novel pharmacotherapies. Because no specific plaque
      targeted therapies are available at present, we give an overview of the current
      pharmacotherapy to treat the vulnerable patient and also discuss potential novel
      therapies to prevent acute coronary events.

PMID- 16596823
TI  - Reciprocal role of vasculogenic factors and progenitor cells in atherogenesis.
AB  - While neovascularization plays an integral role in atherosclerosis, stimulation
      of angiogenesis does not appear to promote atherogenesis. This observation is
      important in view of recent advancements in angiogenic gene and cell therapy
      aimed at promoting new blood vessel growth in humans with vascular disease.
      Endothelial progenitor cells (EPCs) may actually prevent rather than provoke
      intimal thickening and vascular remodeling by promoting re-endothelialization in
      response to vascular trauma, as occurs with percutaneous transluminal vascular
      intervention for treating atherosclerotic vessels. Further support for the
      hypothesis that EPCs continuously repair vascular injury and contribute to the
      rejuvenation of vessels has been derived from animal studies demonstrating that
      serial injection of bone marrow-derived EPCs prevent atherogenesis, but that the
      quantity and quality of these cells deteriorate with aging. This chapter provides
      a summary of the influence of angiogenesis on atheromatous disease. Furthermore,
      the increasingly important relationship between atherosclerosis and newly
      emerging techniques in therapeutic angiogenesis (i.e., gene therapy and cell
      therapy with EPCs) is discussed.

PMID- 16596824
TI  - Gene therapy of atherosclerosis.
AB  - Atherosclerosis and related diseases are the leading cause of death in Western
      world. The disease process begins with the formation of fatty streaks already
      during the first decade of life but does not manifest clinically until several
      decades later. Gene therapy is a potential new way to target multiple factors
      playing a role in the development and progression of atherosclerosis. A great
      number of genes involved in the development of atherosclerosis have been
      identified and have been tested both in vitro and in vivo as potential new
      targets for therapy. Pre-clinical experiments have shown the feasibility and
      safety of several gene therapy applications for the treatment of atherosclerosis
      and clinical trials have also provided evidence for the applicability of gene
      therapy for the treatment of cardiovascular diseases. In this review we discuss
      vectors and potential gene therapy approaches for intervention and therapy of
      atherosclerosis.

PMID- 16596825
TI  - Patterns of child maltreatment referrals among Asian and Pacific Islander
      families.
AB  - Much of the available data on Asian American families who become involved with
      the child welfare system relies on global ethnic categories, such as the category
      Asian/Pacific Islander. To explore the diversity of experience that is hidden by
      such categories, this article analyzes two years of child maltreatment referrals
      for Asian and Pacific Island families in Washington state. The study findings
      show that considerable variation exists within the Asian and Pacific Islander
      population with regard to child protection referrals. Although Asian Americans as
      a whole were less likely to be referred to child protective services than other
      groups, the within group picture that these data capture is considerably more
      complex. Some Asian/Pacific Islander ethnic groups, particularly those which have
      experienced higher levels of social and economic stress, were more at risk of
      child welfare involvement than other groups. Such findings underscore the need
      for child welfare policies and practice that are sensitive to the considerable
      variability within the Asian/Pacific Islander community.

PMID- 16596826
TI  - Health and mental health services for children in foster care: the central role
      of foster parents.
AB  - It is well documented that children enter foster care with special health and
      mental health needs and, while in care, those conditions are often exacerbated.
      However, less attention has been given to foster parents who have the most
      contact with these children. Results are presented from a national study on the
      developmental, health and mental health care needs of children in foster care
      that included foster parents' perspectives and observations. Their role in
      improving child well being is explained and recommendations for policy, practice
      and advocacy also are included.

PMID- 16596827
TI  - Risk assessment in child sexual abuse cases.
AB  - Despite continuing improvements in risk assessment for child protective services
      (CPS) and movement toward actuarial prediction of child maltreatment, current
      models have not adequately addressed child sexual abuse. Sexual abuse cases
      present unique and ambiguous indicators to the investigating professional, and
      risk factors differ from those related to physical abuse and neglect.
      Incorporation of research on risk factors specifically related to sexual offender
      recidivism into existing CPS risk assessment models may improve the ability to
      assess the risk of future sexual maltreatment to children. This article reviews
      the literature on risk factors for sexual offense recidivism and discusses their
      relevance and application to CPS assessment models. An evidence-based model for
      assessing risk in child sexual abuse cases is proposed.

PMID- 16596828
TI  - Child welfare workers: who they are and how they view the child welfare system.
AB  - This article examines the characteristics of child welfare caseworkers, their
      views of the child welfare system, their clients, their agency of employment, and
      child welfare policies, and whether these views vary according to caseworkers'
      characteristics. Quantitative and qualitative methods were used to analyze in
      depth interviews conducted with caseworkers in New York and Chicago. The major
      themes that emerged from the analysis indicate caseworkers believed that the
      child welfare system does not meet the needs of the children in care, lacks the
      resources to appropriately serve clients, and often establishes goals that cannot
      be attained by the biological parents. Caseworkers held negative views of the
      biological parents and, although most described their organization as well
      equipped, almost as many reported that their organization lacked technical,
      administrative, and personnel resources. Caseworkers' views of child welfare
      policies emphasized the need for reforming the system and reevaluating funding
      priorities.

PMID- 16596829
TI  - Thrombolytic therapy for acute ST-segment elevation myocardial infarction: should
      it be given to all patients prior to urgent PCI?

PMID- 16596830
TI  - Antiarrhythmic drug therapy for atrial fibrillation: are the guidelines guiding
      clinical practice?
AB  - The AFFIRM study showed no clear survival advantage for a rhythm versus rate
      control strategy in patients with atrial fibrillation (AF). However, rhythm
      control with antiarrhythmic drugs (AADs) is appropriate in a large number of
      patients with AF. The American College of Cardiology/ American Heart
      Association/European Society of Cardiology AF management guidelines include a
      safety-based algorithm for selection of AAD therapy. Class 1C agents are
      recommended as first-line therapy in patients without or with minimal structural
      heart disease. However, market research and clinical study data indicate a
      growing use of class III agents (mainly amiodarone) despite long-term safety and
      tolerability concerns, suggesting that clinical practice does not adhere to
      current guidelines.

PMID- 16596831
TI  - Life-threatening acute and chronic thromboembolic pulmonary hypertension and
      subclavian vein thrombosis.
AB  - Severe thromboembolic pulmonary hypertension is an infrequent but potentially
      fatal complication of effort thrombosis (Paget-Schroetter syndrome) of the upper
      extremity. It has been sporadically reported in the literature, but in most cases
      has affected young, otherwise healthy athletes. Because this syndrome has been
      rarely described, it is likely underdiagnosed, and optimal evaluation and
      treatment has not been established. We describe three young athletic persons who
      developed thrombosis of the subclavian vein after repetitive motion of the upper
      extremity, and in whom life-threatening pulmonary hypertension resulted from
      acute and chronic pulmonary emboli. We then review the mechanism, clinical
      presentation, diagnosis, and available therapeutic modalities.

PMID- 16596832
TI  - Operating characteristics of the Finapress system to predict elevated left
      ventricular filling pressure.
AB  - BACKGROUND: Dyspnea is a common symptom and can be caused by many different
      conditions. The detection of congestive heart failure (CHF) is sometimes
      difficult. HYPOTHESIS: The pulse amplitude ratio (PAR) measured by the Finapress
      procedure during a Valsalva maneuver can detect elevated left ventricular end
      diastolic pressure (LVEDP) accurately over a wide range of values. METHODS:
      Comparison of the estimated LVEDP by PAR with the invasively measured LVEDP
      before and after ventriculography during coronography was made in 101 consecutive
      stable patients referred for chest pain and/or chronic dyspnea. RESULTS: A
      significant correlation was found between the catheter-measured LVEDP (range 3-40
      mmHg) and the PAR (R2 = 0.70, p < 0.001). The receiver operator characteristics
      (ROC) of the PAR to detect an LVEDP > 15 mmHg can be considered to be excellent,
      with an area under the ROC curve achieving 0.92 (95% confidence interval [CI]
      0.87-0.96; p < 0.001). A PAR of > 0.675 predicted the presence of an LVEDP > 15
      mmHg with a sensitivity of 0.865 (95% CI 0.780-0.926) and a specificity of 0.847
      (95% CI 0.730-0.928). The positive and negative LRs were 5.70 and 0.16,
      respectively. CONCLUSIONS: The observed likelihood ratios confirm that the PAR
      determined by the Finapress procedure may be a useful bedside diagnostic tool in
      patients with cardiac conditions.

PMID- 16596833
TI  - Primary percutaneous coronary intervention in acute myocardial infarction: direct
      transportation to catheterization laboratory by emergency teams reduces door-to
      balloon time.
AB  - BACKGROUND: Primary percutaneous coronary intervention (PCI) is the recommended
      revascularization strategy for patients presenting with acute ST-elevation
      myocardial infarction (STEMI). In most hospitals, transfer of patients with STEMI
      is organized from the emergency site via emergency room (medical and cardiologic
      evaluation) and then to the catheterization laboratory. HYPOTHESIS: In this
      prospective study, we sought to evaluate the effect of a logistic modification in
      this treatment process. METHODS: Local emergency ambulance teams were instructed
      to identify and evaluate patients with STEMI eligible for direct PCI and to
      transport them directly to the cardiac catheterization laboratory for immediate
      percutaneous coronary intervention ("ER bypass"). This study prospectively
      included 74 consecutive patients with acute coronary syndromes (STEMI) and
      compared them with a matched historic control group ("ER evaluation"). Primary
      endpoint was the reduction in door-to-balloon time; secondary endpoint was
      quality of preclinical emergency diagnosis. RESULTS: Median door-to-balloon time
      was reduced by 27 min. Primary interventional success was achieved in 92% of
      patients. Preclinical emergency diagnoses were correct in 95% of patients.
      CONCLUSION: The preclinical emergency diagnosis of STEMI was reliable. Direct
      transport of patients with STEMI to the cardiac catheterization laboratory and
      early preclinical alert by the interventional PCI team significantly reduces door
      to-balloon-times compared with established standard processes-of-care for
      patients considered for primary PCI.

PMID- 16596834
TI  - Characteristics and outcome of octogenarian population referred for myocardial
      perfusion imaging: comparison with non-octogenarian population with reference to
      gender.
AB  - BACKGROUND: Octogenarian patients referred for stress myocardial perfusion
      imaging (MPI) differ from younger (non-octogenarian) patients in that they have
      lower prevalence of risk factors for CAD, but more frequent ischemic events and
      higher cardiac mortality. HYPOTHESIS: The purpose of this study was to
      investigate the efficacy of MPI in octogenarian men and women compared with that
      in the younger population, and to compare the prognostic value of stress MPI in
      both populations. METHODS: We studied 162 consecutive patients aged > or = 80
      years who were referred for stress MPI, and compared them with 253 consecutive
      patients aged < 80 years. Patients completed a questionnaire encompassing
      information about the existence of coronary risk factors, cardiac symptoms,
      coronary artery disease (CAD), myocardial infarction, coronary artery bypass
      graft, percutaneous transluminal coronary angioplasty, and results of stress MPI.
      The patients were followed up for cardiac mortality for a mean of 45 +/- 12
      months. RESULTS: There were 61 women and 101 men (17% of all referrals) with a
      mean age of 83 +/- 3 (range 80-90). Parameters of octogenarian patients
      demonstrated a significantly lower prevalence of non-insulin-dependent diabetes
      mellitus (p < 0.02), hypercholestrolemia (p < 0.001), and smoking (p = 0.001)
      compared with non-octogenarian patients. The prevalence of known CAD was similar,
      but the prevalence of abnormal resting electrocardiogram, left ventricular (LV)
      dilatation, and stress-induced ischemia was significantly higher in octogenarians
      (p < 0.002). Cardiac mortality rate per year was 4.3% in octogenarians versus
      1.3% in the younger population (p < 0.0001). The independent predictors according
      to MPI of cardiac death were LV dilatation and presence of ischemia in
      octogenarians, and severity of ischemia in non-octogenarians. CONCLUSIONS: The
      octogenarian population referred for stress single-photon emission computed
      tomography differed from the non-octogenarian group in that it had a lower
      prevalence of risk factors for CAD, but more frequent ischemic events and higher
      cardiac mortality; however, MPI variables predict adverse outcome in both
      populations.

PMID- 16596835
TI  - Prognosis of patients with left ventricular diastolic pressure abnormality: a
      long-term survival study in patients without coronary artery disease.
AB  - BACKGROUND: Given that an elevated left ventricular (LV) end-diastolic pressure
      reflects an abnormality of diastolic function, we analyzed the outcome of this
      finding in patients without coronary artery disease (CAD). HYPOTHESIS: The degree
      to which diastolic dysfunction influences mortality has been confounded in most
      studies by CAD and advanced age. METHODS: We performed a retrospective study of
      876 patients with normal coronary arteries on arteriography. Of these, 115
      patients had a left ventricular end-diastolic pressure of > or = 15 mmHg with an
      ejection fraction (EF) > or = 50%. We compared the mortality in this group (Group
      A) with the reported outcome in the general population, adjusted for age, gender,
      and race, as well as the mortality of a group of patients from the same cohort
      (Group B) with both diastolic and systolic dysfunction (n = 60), defined as a
      LVEF < 50%. RESULTS: Follow-up was for a mean of 63 months. In Group A, all-cause
      mortality was 5% (six patients); two deaths were from cardiac causes. The mean
      annual mortality in this group (1.2%) was similar to the adjusted annual
      mortality of the general population (1.1%), and it was significantly lower than
      the annual mortality (6%) in Group B (p < 0.03). CONCLUSIONS: Our study results
      indicate that diastolic dysfunction with a normal EF, in the absence of CAD and
      systolic dysfunction, has an excellent prognosis over a long period (5-6 years).

PMID- 16596836
TI  - Plasma adrenomedullin relation with Doppler-derived dP/dt in patients with
      congestive heart failure.
AB  - BACKGROUND: Increased circulating adrenomedullin (AM) concentration has been
      reported in congestive heart failure (HF) and considered as a possible marker of
      cardiac dysfunction. HYPOTHESIS: The study was undertaken to assess the
      relationship between circulating AM concentration and left ventricular (LV)
      functional state, estimated by echo-Doppler techniques in patients with mild to
      moderate HF and different degrees of LV dysfunction. METHODS: Plasma AM, B-type
      natriuretic peptide (BNP), and N-terminal (NT) proBNP levels were measured in 55
      patients with HF (New York Heart Association [NYHA] I n = 8, II n = 26, III n =
      21) and in 20 controls; dP/dt was calculated by the Doppler tracing of the mitral
      regurgitation jet. RESULTS: The study was completed in 51 patients.
      Adrenomedullin levels were higher than in controls (19.2 +/- 1.4 vs. 13.3 +/-
      0.7, p < 0.005) and elevated in proportion to NYHA functional class. B-type
      natriuretic peptide and NT-proBNP were 344 +/- 67 vs. 12 +/- 2 pg/ml and 2196 +/-
      623 vs. 52 +/- 4 pg/ml, respectively (p < 0.0001); dP/dt was better related to AM
      (r = 0.582, p < 0.001) than to the other peptides. Adrenomedullin was
      significantly (p < 0.001) different between patients grouped according to the
      dP/dt cut-off predictive of event-free survival. CONCLUSIONS: The combination of
      depressed contractility and increased AM may provide a clue for further
      characterization of the severity of LV dysfunction in HF, independent of baseline
      LV ejection fraction.

PMID- 16596838
TI  - Left-ventricular rupture detected with contrast-enhanced computed tomography.

PMID- 16596839
TI  - Pathognomonic echocardiographic features of carcinoid syndrome.

PMID- 16596837
TI  - "Sensing alternans" in a patient with a newly implanted pacemaker.
AB  - This report describes the case of an 80-year-old man with a history of coronary
      artery disease who presented with acute pericarditis secondary to pacemaker lead
      perforation of the ventricular wall 2 days after undergoing dual lead pacemaker
      implantation. The electrocardiogram revealed sinus rhythm with an intra-atrial
      conduction delay and intermittent failure of atrial sensing as evidenced by
      alternating atrial spikes in every other P wave. The noted pericardial effusion
      and the likely shifting of the atrial lead with each alternate beat caused the
      "sensing alternans" that was seen on the admission electrocardiogram.

PMID- 16596841
TI  - Health IT Czar focuses on interoperability.

PMID- 16596840
TI  - Otto Loewi and the chemical transmission of vagus stimulation in the heart.

PMID- 16596843
TI  - How to choose the right clinical engineering software.

PMID- 16596842
TI  - Issues to consider when rolling out point-of-care technology.

PMID- 16596844
TI  - Telemedicine program delivers healthcare services far and wide.

PMID- 16596845
TI  - Eight steps to integrating security standards.

PMID- 16596846
TI  - Tagging the issues surrounding auto-ID labels.

PMID- 16596847
TI  - Portable analysis tools help solve networking problems.

PMID- 16596848
TI  - Managing your wireless spectrum... Making wireless technology work in your
      hospital.

PMID- 16596849
TI  - Lessons learned from... Interference to wireless medical telemetry service
      systems.

PMID- 16596850
TI  - Evaluating EMI in a multi-hospital facility.

PMID- 16596851
TI  - Growth of wireless technology in healthcare institutions.
AB  - As wireless technologies evolve and interoperate, the practical application for
      healthcare providers and organizations grows exponentially. By providing
      increased access to patient data, decision-making tools (e.g., computer aided
      decision systems such as ECG analysis programs), error reduction systems (i.e.,
      pharmaceutical error prevention software), the benefits of wireless technology
      can be immense. However, as with all technological innovations, wireless systems
      must be carefully planned and managed. As the wireless spectrum becomes more
      crowded with both complementary and competing systems, bandwidth utilization and
      the potential for interference grows greatly. Clinical engineering personnel need
      to be actively involved in the management of wireless system management within a
      healthcare facility to avoid interference problems that could disrupt patient
      care, especially as the deployment of wireless systems expands. Additionally,
      public exposure to RF energy in a healthcare setting may need to be monitored and
      evaluated as the utilization of this energy spectrum continues to grow. All
      manufacturers of RF emitting devices are required to list the specific absorption
      rate of their specific device. However, there is no monitoring of the cumulative
      effect of multiple devices and systems. As of press time, this has not been an
      issue. But it is something to consider as we continue to find useful applications
      for this technology.

PMID- 16596852
TI  - Virtual handshake: get to know your home and enterprise networks.

PMID- 16596853
TI  - Pay: don't scapegoat nurses.

PMID- 16596854
TI  - Battle lines drawn on employment rights as privatisation beckons.

PMID- 16596855
TI  - How to save the NHS.
AB  - A system of payment by results will mean NHS trusts and independent providers
      will be competing for patients and will be rewarded for improved services. There
      will be a fixed tariff for the treatment of individual patients. Tariffs will be
      adjusted to reflect more and less expensive areas of the country. Payments will
      depend on whether the procedure is elective or non-elective. The tariff will pay
      more above a particular age threshold or if there are unexpected complications.

PMID- 16596856
TI  - Crime scene.
AB  - Nurses in Chichester are carving out new roles as forensic nurse practitioners
      (FNPs). Working closely with the police, they are making a significant
      contribution to the safety and welfare of detainees. The role of FNP attracts
      nurses from diverse disciplines. Nursing skills translate well to the need for
      accurate documentation. They work closely with forensic medical examiners. There
      are several models of service delivery around the UK.

PMID- 16596858
TI  - Simple words of wisdom.

PMID- 16596857
TI  - Designed to perfection.

PMID- 16596859
TI  - Speaking up for patients.

PMID- 16596860
TI  - Barriers to accurate drug calculations.
AB  - AIM: To examine the drug calculation skills of nursing students. METHOD: A
      mathematics test and a structured questionnaire were used to determine level of
      skill and perceptions related to mathematics. RESULTS: The test revealed
      difficulties in multiplying fractions and interpreting information, and the
      questionnaire showed that drug calculation skills were related to education
      level, confidence and enjoyment of maths at school. CONCLUSION: Nursing students
      should be given opportunities to improve their maths skills alongside developing
      their knowledge of drug calculations in clinical practice.

PMID- 16596861
TI  - Nurse-led cardiac clinics for adults with coronary heart disease.
AB  - This information on best practice is based on a systematic review of research,
      published by Blackwell Publishing Asia and conducted by the Centre for Evidence
      based Nursing South Australia, a collaborating centre of the Joanna Briggs
      Institute (JBI). The primary references on which this information is based are
      provided in the systematic review report available online via Blackwell Synergy
      www.blackwell-synergy.com and to members of the institute via the web site:
      www.joannabriggs.edu.au. This information sheet covers the following: Nurse-led
      education and self-help. Education and motivational interview. Audit and recall.
      Secondary prevention.

PMID- 16596862
TI  - Malignant hyperthermia.
AB  - Malignant hyperthermia, also known as malignant hyperpyrexia, is a
      pharmacogenetic condition which can develop during general anaesthesia and can be
      fatal. The author suggests that more awareness of the condition is needed by ward
      based nurses who are involved with patients undergoing surgery. The article
      describes the management of the condition, the nursing care and the screening
      available for susceptible patients.

PMID- 16596863
TI  - The assessment and management of venous thromboembolism.
AB  - This article examines venous thromboembolism (VTE) and offers guidance on its
      prevention. VTE is a potentially fatal condition, which can be prevented using
      both pharmacological and mechanical methods. Nursing staff should be aware of the
      risk factors that predispose patients to venous thromboembolism and ensure that
      high-risk patients receive the prophylaxis they require.

PMID- 16596865
TI  - World of opportunity.

PMID- 16596864
TI  - A proactive approach to asthma.

PMID- 16596866
TI  - Waiting for your call.

PMID- 16596868
TI  - The collider calamity.

PMID- 16596867
TI  - Constructive feedback.

PMID- 16596869
TI  - The check is in the mail.

PMID- 16596870
TI  - Lifting the winter dark.

PMID- 16596871
TI  - Turning yellow.

PMID- 16596872
TI  - Taking sides.

PMID- 16596873
TI  - Survival of the smallest.

PMID- 16596874
TI  - Crystal steer.

PMID- 16596875
TI  - Lady luck.

PMID- 16596876
TI  - As luck would have it.

PMID- 16596877
TI  - The prostitutes' union.

PMID- 16596878
TI  - The mysterious origins of solar flares.

PMID- 16596880
TI  - Computing with quantum knots.

PMID- 16596881
TI  - Why are some animals so smart?

PMID- 16596879
TI  - New hope for defeating rotavirus.

PMID- 16596882
TI  - Hybrid vehicles gain traction.

PMID- 16596883
TI  - An antibiotic resistance fighter.

PMID- 16596884
TI  - Does globalization help or hurt the world's poor?

PMID- 16596885
TI  - Big squeeze.

PMID- 16596886
TI  - Why is oil usually found in deserts and arctic areas?

PMID- 16596887
TI  - Why does lactic acid build up in muscles?

PMID- 16596888
TI  - A foundation for the future.

PMID- 16596889
TI  - Simplifying the star excursion balance test: analyses of subjects with and
      without chronic ankle instability.
AB  - STUDY DESIGN: Case control study. OBJECTIVES: The objectives of this study are:
      (1) to perform factor analyses on data from the 8 components of the star
      excursion balance test (SEBT) in subjects with and without chronic ankle
      instability (CAI) in an effort to reduce the number of components of the SEBT,
      (2) to assess the relationships between performance of the different reach
      directions using correlation analyses, and (3) to determine which components of
      the SEBT are most affected by CAI. BACKGROUND: The SEBT is a series of 8 lower
      extremity-reaching tasks purported to be useful in identifying lower extremity
      functional deficits. METHODS AND MEASURES: Forty-eight young adults with
      unilateral CAI (22 males, 26 females; mean +/- SD age, 20.9 +/- 3.2 years; mean
      +/- SD height, 173.6 +/- 11.1 cm; mean +/- SD mass, 80.1 +/- 22.1 kg) and 39
      controls (23 males, 16 females; mean +/- SD age, 20.7 +/- 2.4 years; mean +/- SD
      height, 174.1 +/- 12.9 cm; mean +/- SD mass, 75.1 +/- 18.6 kg) performed 3 trials
      of the 8 tasks with each of their limbs. Separate exploratory factor analyses
      were performed on data for involved limbs of the CAI group, uninvolved limbs of
      the CAI and control groups, and both limbs of the CAI and control groups. Pearson
      product moment correlations were calculated to identify the relationships between
      the different reach directions. A series of eight 2 x 2 analyses of variance were
      calculated to determine the influence of group (CAI, control) and side (involved,
      uninvolved) on performance of the 8 tasks. RESULTS: For all 3 factor analyses,
      only 1 factor in each analysis produced an eigenvalue greater than 1 and the
      posteromedial reach score was the most strongly correlated task with the computed
      factor (alpha > .90), although all 8 tasks produced alpha scores greater than
      .67. Bivariate correlations between specific reach directions ranged from .40 to
      .91. Subjects with CAI reached significantly less on the anteromedial, medial,
      and posteromedial directions when balancing on their involved limbs compared to
      their uninvolved limbs and the side-matched limbs of controls. CONCLUSIONS: The
      posteromedial component of the SEBT is highly representative of the performance
      of all 8 components of the test in limbs with and without CAI. There is
      considerable redundancy in the 8 tasks. The anteromedial, medial, and
      posteromedial reach tasks may be used clinically to test for functional deficits
      related to CAI in lieu of testing all 8 tasks. There is a need for a hypothesis
      driven study to confirm the results of this exploratory study.

PMID- 16596890
TI  - The Penn shoulder score: reliability and validity.
AB  - STUDY DESIGN: Psychometric evaluation of a cross-sectional survey. OBJECTIVES:
      The purpose of this study was to examine the psychometric properties of
      reliability and validity of the Penn Shoulder Score (PSS). BACKGROUND: Shoulder
      outcome measures are used to assess patient self-report levels of pain,
      satisfaction, and function. The PSS is a 100-point shoulder-specific self-report
      questionnaire consisting of 3 subscales of pain, satisfaction, and function. This
      scale has been utilized in the literature. However, the measurement properties of
      reliability and validity, including responsiveness, of the PSS subscales and
      overall scale need to be established. METHODS AND MEASURES: Patients (n = 40)
      with shoulder disorders undergoing a course of outpatient physical therapy
      completed the PSS at initial visit and again within 72 hours to assess test
      retest reliability. The Constant Shoulder Score (CSS) and the American Shoulder
      and Elbow Surgeons Shoulder Score (ASES) were also completed at the initial visit
      and compared to the PSS to assess convergent construct validity. A separate
      cohort of patients (n = 109) completed the PSS at initial visit and 4 weeks
      later. These scores were used to assess internal consistency and responsiveness.
      RESULTS: Reliability analysis revealed a test-retest ICC2,1 of 0.94 (95% CI, 0.89
      0.97). Internal consistency analysis revealed a Cronbach alpha of 0.93. The
      standard error of measurement (SEM) was +/- 8.5 scale points (based on a 90% CI)
      and the minimal detectable change (MDC) was +/- 12.1 scale points (based on a 90%
      CI). The minimal clinically important difference (MCID) for improvement was 11.4
      points. Pearson product moment correlation coefficients between the PSS and the
      CSS and ASES were 0.85 and 0.87, respectively. Responsiveness analysis revealed
      an effect size of 1.01 and a standardized response mean of 1.27. CONCLUSIONS:
      This study has demonstrated that the PSS is a reliable and valid measure for
      reporting outcome of patients with various shoulder disorders.

PMID- 16596891
TI  - Diagnosis and treatment of cervical radiculopathy using a clinical prediction
      rule and a multimodal intervention approach: a case series.
AB  - STUDY DESIGN: Case series. OBJECTIVES: To describe an established method of
      diagnosing cervical radiculopathy (CR) using a clinical prediction rule (CPR),
      and to describe the management of 6 patients using intermittent cervical traction
      (ICT), thoracic thrust joint manipulation (TJM), and exercise. BACKGROUND: Many
      patients present with unilateral arm pain without having undergone magnetic
      resonance imaging (MRI) of the cervical spine. Using a CPR has demonstrated high
      levels of specificity to rule in cervical radiculopathy. ICT and manual therapy
      (including thoracic TJM) are widely used in clinical settings to treat cervical
      radiculopathy. CASE DESCRIPTION: Six patients (3 men, 3 women) were diagnosed
      with cervical radiculopathy using the CPR. All patients were treated with ICT,
      thoracic TJM, and exercise. The Northwick Park Neck Questionnaire served as the
      outcome measure. OUTCOMES: The CPR accurately identified CR (secondary to a disc
      herniation) in 4 out of 4 patients when compared to the results of a reference
      standard (MRI). Six patients were seen from 5 to 18 sessions over a 19- to 56-day
      period. Reduction in Northwick Park Neck Questionnaire scores ranged from 13% to
      88%. One patient did not improve significantly and underwent neck surgery.
      DISCUSSION: Using the CPR may be beneficial in diagnosing CR, so the clinician
      can devise a plan of care and assess treatment outcomes in a relatively
      homogenous group of patients. It is possible that a treatment regimen of ICT,
      thoracic TJM, and exercise will aid in centralizing radicular symptoms and
      improving functional outcomes in patients with CR.

PMID- 16596892
TI  - Methodological quality of randomized controlled trials of spinal manipulation and
      mobilization in tension-type headache, migraine, and cervicogenic headache.
AB  - STUDY DESIGN: Literature review of quality of clinical trials. OBJECTIVE: To
      determine the methodological quality of published randomized controlled trials
      that used spinal manipulation and/or mobilization to treat patients with tension
      type headache (TTH), cervicogenic headache (CeH), and migraine (M) in the last
      decade. BACKGROUND: TTH, CeH, and M are the most prevalent types of headaches
      seen in adults. Individuals who have headaches frequently use physical therapy,
      manual therapy, or chiropractic care. Randomized controlled trials are considered
      an optimal method with which to assess the efficacy of any intervention. METHODS:
      Computerized literature searches were performed in MEDLINE, EMBASE, COCHRANE,
      AMED, MANTIS, CINHAL, and PEDro databases. Randomized controlled trials in which
      spinal manipulation and/or mobilization had been used for TTH, CeH, and M
      published in a peer-reviewed journal as full text, and with at least 1 clinically
      relevant outcome measure (ie, headache intensity, duration, or frequency) were
      reviewed. The methodological quality of the studies was assessed independently by
      2 reviewers using a set of predefined criteria. RESULTS: Only 8 studies met all
      the inclusion criteria. One clinical trial evaluated spinal manipulation and
      mobilization together, and the remaining 7 assessed spinal manipulative therapy.
      No controlled trials analyzing exclusively the effects of spinal mobilization
      were found. Methodological scores ranged from 35 to 56 points out of a
      theoretical maximum of 100 points, indicating an overall poor methodology of the
      studies. Only 2 studies obtained a high-quality score (greater than 50 points).
      No significant differences in quality scores were found based on the type of
      headache investigated. Methodological quality was not associated with the year of
      publication (before 2000, or later) nor with the results (positive, neutral,
      negative) reported in the studies. The most common flaws were a small sample
      size, the absence of a placebo control group, lack of blinded patients, and no
      description of the manipulative procedure. CONCLUSIONS: There are few published
      randomized controlled trials analyzing the effectiveness of spinal manipulation
      and/or mobilization for TTH, CeH, and M in the last decade. In addition, the
      methodological quality of these papers is typically low. Clearly, there is a need
      for high-quality randomized controlled trials assessing the effectiveness of
      these interventions in these headache disorders.

PMID- 16596893
TI  - A dynamic extensor brace reduces electromyographic activity of wrist extensor
      muscles in patients with lateral epicondylalgia.
AB  - STUDY DESIGN: Semiexperimental study. OBJECTIVE: To investigate the effect of an
      external wrist extension force on extensor muscle activity during hand gripping
      in patients with lateral epicondylalgia. BACKGROUND: Lateral epicondylalgia or
      "tennis elbow" is a common, often disabling ailment affecting millions of people.
      An optimal treatment strategy remains to be identified. The use of an external
      wrist extension force may reduce the extensor muscle activity during gripping in
      these patients. METHODS: Muscle activity of the extensor carpi radialis brevis
      (ECRB), extensor digitorum communis (EDC), and extensor carpi radialis longus
      (ECRL) was measured using surface EMG. Subjects gripped at an intensity of 10%,
      20%, and 30% of the maximum voluntary contraction (MVC) force with and without
      the dynamic extensor brace and with and without an applied external wrist
      extension force of 1%, 2%, and 3% of MVC. RESULTS: At all levels of MVC gripping,
      the EMG signal of the ECRB and EDC were significantly lower for gripping with
      than without brace. An extension force of 3% of the MVC force significantly
      reduced the EMG signal of all muscles in almost all measurement conditions.
      CONCLUSIONS: The results of this study indicate that the dynamic extensor brace
      as well as the external extension force significantly reduced the EMG signal of
      the wrist extensor muscles during gripping in patients with lateral
      epicondylalgia. Based on these results, the dynamic extensor brace could be a
      promising new intervention for lateral epicondylalgia.

PMID- 16596894
TI  - Validity of 3 clinical techniques for the measurement of static foot posture in
      older people.

PMID- 16596895
TI  - Breast cancer in African American women: nursing essentials.
AB  - Breast cancer impacts all population groups. However, when measures of mortality
      and length of survival are compared by racial/ethnic groups, African American
      women are noted to bear a disproportionate burden. In an era where evidence-based
      practice is the standard, it is imperative that nurses engaged in practice with
      women within acute care and community-based settings, have a breadth of knowledge
      of the anatomy and pathophysiology of breast cancer, are knowledgeable of the
      standards of breast care, and knowledgeable of the availability and accessibility
      of breast care resources within their service area. This report provides an
      overview for nurse of trends in breast cancer morbidity and mortality among
      African American women, breast cancer pathology, breast cancer screening
      guidelines and breast cancer clinical practice recommendations.

PMID- 16596896
TI  - Getting ready: developing an educational intervention to prepare African American
      women for breast biopsy.
AB  - Focus groups with African American women who had experienced a breast biopsy were
      conducted during the process of "getting ready" for a breast biopsy educational
      study in which the intervention's educational materials and study instruments
      were developed and pre-tested. Recommendations were made for revising the breast
      biopsy educational booklet. As a result of the focus group discussions, changes
      were made in several of the graphics, the design and size of the booklet, and the
      tone of the piece. In addition, language describing the biopsy procedure was
      further simplified. The outcomes of this study were culturally tailored study
      materials to be used in an educational intervention to prepare African American
      women undergoing a breast biopsy procedure.

PMID- 16596897
TI  - Religion and spirituality: influence on health/risk behavior and cancer screening
      behavior of African Americans.
AB  - In spite of the diversity in the principles, expression and practice, it is
      believed that significant improvements can occur in the health status of African
      Americans if health education and outreach efforts are presented and promoted
      through religious, spiritual and faith-based venues. Several reports published in
      the peer-reviewed literature address issues related to religion, spirituality and
      cancer control among African Americans. This growing body of literature describes
      outcomes of several cancer prevention and control programs designed for and
      conducted within the African American faith community. However, few efforts have
      been undertaken to examine the influence of religion and spirituality on
      health/risk behavior and cancer screening practices of African Americans within
      the faith community. This report presents the outcomes of an exploratory study
      undertaken to examine the influence of religion and spirituality on the
      health/risk behavior and cancer screening practices of African American
      congregants. Data suggest a need for tailored and targeted health education,
      outreach and programming among the targeted group of congregants focused
      specifically on tobacco control, diet and nutrition, exercise and physical
      activity, weight management, and cancer screening. The same appears to be the
      case relative to the need for education, outreach and programming focused on
      communication with primary care providers.

PMID- 16596898
TI  - African American women with breast cancer and their spouses' perception of care
      received from physicians.
AB  - Several studies have been conducted which have examined the communication
      patterns and interpersonal relationships among minority patients and their
      physicians. These studies suggest that there are differences in the care received
      from physicians based on the racial and cultural background of the patient.
      However, little is known about the interpersonal relationships and communication
      patterns of AA couples coping with a breast cancer diagnosis and their
      physicians. This report presents the outcomes of a qualitative study undertaken
      to examine the perceptions of breast cancer care rendered by physicians to
      African American couples. The AA couples involved in the study reported that the
      care they received was compassionate, competent, comprehensive and comparable to
      other women. Each of these qualities was identified by as being essential to
      quality patient care.

PMID- 16596899
TI  - Cancer fatalism and breast cancer screening in African American women.
AB  - Despite significant advances in science, medicine, and technology African
      American women are more likely to die from breast cancer than Caucasian women.
      There is a growing body of literature that describes strategies to improve breast
      cancer screening among African American women. However, data suggest that African
      American women, compared to Caucasian women, are less likely to participate in
      regular breast cancer screening. The belief that a diagnosis of cancer will
      result in death has been identified as a potential barrier to cancer screening in
      African American population groups. However, research examining the degree to
      which perceptions of fatalism influence breast cancer screening in culturally and
      ethnically diverse population groups is scant. This repot describes the outcomes
      of a study undertaken to examine relationships between perceptions of cancer
      fatalism and breast cancer screening in African American women. Findings support
      the postulation that fatalism negatively influences health promoting practices
      such as breast cancer screening. However, contrary to prior research findings age
      was observed to be inversely associated with cancer fatalism.

PMID- 16596900
TI  - An approach to reducing disparities in breast cancer in the United States Virgin
      Islands.
AB  - Problems resulting in disparities in breast cancer detection and care are not
      limited to the mainland United States. A review of 2002 data reported by the CDC
      Behavioral Risk Factor Surveillance System revealed similar concerns for women
      residing on the U.S. Virgin Islands. This report provides a summary of data
      highlighting trends associated with breast cancer detection and control in the U.
      S. Virgin Islands and a summary of efforts undertaken by faculty and students
      from the University of the Virgin Islands to address them.

PMID- 16596901
TI  - African American community breast health education: a pilot project.
AB  - This paper reports the results of a project designed to examine the effectiveness
      of a Train the Trainer breast health education and screening program for African
      American, elderly and underserved women residing in the greater Nashville area.
      The project aimed to identify a cadre of women from the community willing to
      serve as leaders advocated and peer breast health educators. Data collected from
      the community leaders and the women from the local community during the course of
      the project suggest that the Train the Trainer model was well suited to provide
      education, support and breast cancer resource referral to women residing within
      this rural Tennessee community.

PMID- 16596902
TI  - Assisted reproduction and gender selection: "why boys?".

PMID- 16596903
TI  - Serum beta-hCG titers do not predict ruptured ectopic pregnancy.
AB  - OBJECTIVE: To study the relationship of serum beta-hCG titers in unruptured (U)
      vs. ruptured (R) tubal ectopic pregnancies. METHOD: 183 consecutive tubal ectopic
      pregnancies, confirmed by surgery and/or pathology, were classified as unruptured
      (n=108), or ruptured (n=75). Serum beta-hCG was noted directly before the
      surgery. Patients treated with methotrexate were excluded. The two groups were
      compared for patient age, gravidity (G), parity (P), gestational age at rupture,
      and serum beta-hCG level. Differences were analyzed using the Student's paired t
      test. RESULTS: No significant differences were seen for patient age, G or P
      between the two groups (U vs. R). Gestational age at rupture was significantly
      higher (p = 0.01) in the ruptured ectopics (U: mean = 6.9 wks., s.d.= 2.2 wks; R:
      mean = 7.7 wks, s.d. = 2.5 wks). The range in serum beta-hCG was broad for both
      groups. For U: range = 15-89,504 I.U./L, mean 10,620 I.U./L, s.d. = 17,521
      I.U./L. For R: range = 8-75,071 I.U./L, mean = 11,907 I.U./L, s.d. = 17,320
      I.U./L (P > .25-N.S.). CONCLUSIONS: Serum beta-hCG by itself cannot predict
      whether a tubal ectopic pregnancy is likely to be ruptured; there is no safe
      lower limit in hCG titer below which ruptured ectopic is not seen.

PMID- 16596904
TI  - Sepsis due to gestational psittacosis: A multidisciplinary approach within a
      perinatological center--review of reported cases.
AB  - Chlamydia psittaci is associated with significant morbidity and mortality during
      pregnancy, and its rarity can delay early diagnosis and treatment. A farmer's
      wife presented at 31 weeks with febrile illness and developed signs of septic
      shock, indicating immediate delivery. The child developed uneventfully. The
      mother survived after symptomatic mechanical ventilation, including
      extracorporeal lung assistance, for 11 days due to multi-organ failure. Only two
      weeks after admission antibody titres against Chlamydia were rising. The placenta
      demonstrated acute intervillositis and destruction of throphoblastic cells.
      Retrospectively, the infection was presumed to derive from infected pregnant
      sheep. Pregnant women should be advised to avoid contact with sheep and their
      gestational products. Proper history, early recognition and appropriate
      management is mandatory for survival of both mother and child.

PMID- 16596905
TI  - Seminal hyperviscosity is associated with poor outcome of controlled ovarian
      stimulation and intrauterine insemination: a prospective study.
AB  - OBJECTIVE: To determine the relationship between seminal hyperviscosity and
      pregnancy outcome in patients undergoing ovarian hyperstimulation and
      intrauterine insemination (IUI). METHODS: Patients were enrolled in the study
      between October 2002 and December 2003 at the Toronto Centre for Advanced
      Reproductive Technology. This was a prospective trial that included 37 infertile
      couples with abnormal seminal viscosity who underwent 57 insemination cycles as
      treatment for infertility (group I) and 37 couples undergoing 51 IUI cycles
      during the same time period, with normal semen viscosity, who served as controls
      (group II). Cycles were stimulated using either gonadotropin (FSH) only or FSH
      combined with an aromatase inhibitor, and raw semen processed for intrauterine
      insemination using swim-up or density gradient. Results-The mean number (+/-SD)
      of IUI cycles was 1.93 +/- 1.42 per patient (range 1 to 7 cycles) in group I and
      2.4 +/- 1.05 (range 1 to 4) in group II. The overall pregnancy rate (PR) was 14%
      (8/57) and 11.8% (6/51) per cycle, and 21.6% (8/37) and 16.2% (6/37) per patient
      in group I and in group II, respectively. Among patients where the male had
      seminal hyperviscosity, five (62.5%) pregnancies miscarried in the first
      trimester; there was no miscarriage in the control group. CONCLUSION: The high
      miscarriage rate in couples with semen hyperviscosity may be attributed to
      biophysical alterations or chemical changes of the ejaculate that could impact
      sperm quality despite normal sperm parameters on semen analysis.

PMID- 16596906
TI  - Placenta previa and accreta complicated by amniotic fluid embolism.
AB  - BACKGROUND: The simultaneous occurrence of placenta previa and placenta accreta
      in patients who had previous low transverse cesarean delivery is presently well
      established. However, the sequence of previous cesarean delivery followed by
      placenta previa and accreta in a patient who also experiences a premature rupture
      of membranes as well as amniotic fluid embolism (AFE) is a rare obstetric
      phenomenon. CASE: A 24-year-old woman, para 2 with two previous cesarean
      deliveries, at 32 weeks' gestation by last menstrual period, was admitted with
      premature rupture of membranes. A repeat cesarean delivery (CD) was done.
      Excessive hemorrhage occurred, necessitating a hysterectomy. Also, the patient
      developed an amniotic fluid embolism. CONCLUSION: Placenta previa and placenta
      accreta may be observed in patients who have a previous CD scar and in whom AFE
      develops suddenly and unexpectedly. AFE, a condition with complex pathogenesis,
      presents a number of challenges, with the patient undergoing serious
      complications that may include massive hemorrhage, disseminated intravascular
      coagulopathy, and death. The obstetrician should be alert to the symptoms of AFE,
      and if they occur should begin prompt and aggressive treatment.

PMID- 16596907
TI  - Relationship of reproductive cycle-associated and non-reproductive cycle
      associated psychological problems in women.
AB  - OBJECTIVE: To determine the frequency of past psychological problems associated
      with the reproductive cycle in women seeking routine gynecological care. METHODS:
      Three hundred and sixty-eight women of menopausal age seen at a university
      medical center gynecology clinic were mailed a questionnaire requesting
      information about past mood or anxiety problems associated with specific
      reproductive cycle or hormone use times, such as the premenstruum, pregnancy,
      postpartum, perimenopause, following total hysterectomy with bilateral salpingo
      oophorectomy, and during oral contraceptive or hormone replacement treatment. Chi
      square analysis was done between groups categorized as with and without
      reproductively associated psychological problems (RAPP) and with or without non
      reproductively related psychological problems (non-RAPP). Relative risk of women
      with RAPP having non-RAPP also was calculated. Results-One hundred thirteen women
      returned the questionnaire. Fifty percent of these women reported a past history
      of reproductive cycle-associated psychological problems (RAPP). Of these, 37%
      also reported psychological problems at times in their lives not associated with
      particular reproductive cycle (non-RAPP) times. However, of the 50% of women who
      reported no history of RAPP, only 14% reported non-RAPP. This was a significant
      difference between the groups (p = .0064). There was also a 2.7 times greater
      risk of women with RAPP also having non-RAPP (RR 2.7). CONCLUSIONS: Women with
      reproductively associated psychological problems have a greater risk of also
      having psychological problems at non-reproductively associated times.

PMID- 16596908
TI  - Severe and acute maternal morbidity: Lithuanian experience and review.
AB  - OBJECTIVE: To measure the incidence of severe acute maternal morbidity (SAMM) and
      to find the risk factors that could be useful in trying to predict the
      development of SAMM. METHODS: The data were collected prospectively in 7
      maternity units from different Lithuanian regions over a 1-year period. Every
      woman with a clinical diagnosis of severe preeclampsia, eclampsia, Hemolysis,
      Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome, severe
      hemorrhage, uterine rupture, or severe sepsis during pregnancy or delivery or
      until the 42nd day post partum was included after verification of diagnosis by
      using clinical criteria. RESULT: One hundred and six cases of SAMM and one
      maternal death were identified during the study among 13,399 deliveries
      (7.91/1000 deliveries 95% CI 6.48-9.56). There were 57 cases of severe
      preeclampsia, 3 cases of eclampsia, 38 cases of severe hemorrhage, 3 cases of
      uterine rupture, and 4 cases of severe sepsis. One maternal death occurred due to
      HELLP syndrome, so the case-fatality ratio for severe morbidity was 0.99%.
      CONCLUSIONS: The incidence of SAMM and case-fatality rate in Lithuania are
      similar to those in other European countries. The main risk factors for SAMM were
      previous peripartum hemorrhage, previous hypertension, previous renal diseases,
      lack of antenatal care, and dystocia.

PMID- 16596909
TI  - Earning continuing education credits from Anesthesia Progress.

PMID- 16596910
TI  - A survey of pain, pressure, and discomfort induced by commonly used oral local
      anesthesia injections.
AB  - Intraoral local anesthesia is essential for delivering dental care. However, it
      is often perceived by some patients as the most painful and in some instances as
      the only painful part of the treatment, leading in extreme cases to avoidance of
      dental care. The present study measured the variables of pain, pressure, and
      discomfort caused by 4 commonly used local anesthesia injections: local
      infiltration, mental nerve block, inferior alveolar nerve block, and periodontal
      ligament injections. Patients were asked to grade pain, discomfort, and pressure
      on a visual analog scale as associated with needle insertion, operator finger
      position in the mouth, and pressure at injection. The inferior alveolar injection
      was graded to be the most painful followed by periodontal ligament and then
      mental nerve block injections. The periodontal ligament injections yielded the
      highest pressure scores. The inferior alveolar block injection yielded
      significantly more discomfort than local infiltration and mental nerve block
      injections when comparing finger and needle position. Local infiltration in the
      anterior maxillary region yielded the highest needle insertion and finger
      position discomfort scores. The present study suggests that the dental operator
      should be aware of local anesthesia injection pain, pressure, and discomfort
      together with efficacy of technique.

PMID- 16596911
TI  - Zaleplon (Sonata) oral sedation for outpatient third molar extraction surgery.
AB  - Zalpelon was compared with triazolam for oral sedation in a third molar surgery
      model using a double-blind crossover design. Factors such as anxiolysis, amnesia,
      and quality of sedation were assessed. Of the 14 participants who completed the
      study, zaleplon sedation was found to be similar to triazolam sedation in all
      regards except that recovery from zaleplon was more rapid.

PMID- 16596912
TI  - Anesthetic efficacy of bupivacaine solutions in inferior alveolar nerve block.
AB  - The purpose of this study was to compare the anesthetic efficacy of 2 bupivacaine
      solutions. Twenty-two volunteers randomly received in a crossover, double-blinded
      manner 2 inferior alveolar nerve blocks with 1.8 mL of racemic bupivacaine and a
      mixture of 75% levobupivacaine and 25% dextrobupivacaine, both 0.5% and with 1 :
      200,000 epinephrine. Before and after the injection, the first mandibular
      premolar was evaluated every 2 minutes until no response to the maximal output
      (80 reading) of the pulp tester and then again every 20 minutes. Data were
      analyzed using the Wilcoxon paired test and the paired t test. No differences
      were found between the solutions for onset and duration of pulpal anesthesia and
      duration of soft tissue anesthesia (P > .05). It was concluded that the solutions
      have similar anesthetic efficacy.

PMID- 16596913
TI  - Benzocaine-induced methemoglobinemia.
AB  - A case is reported in which a patient developed methemoglobinemia-induced
      cyanosis while under general anesthesia during surgery for multiple fascial space
      infections. The cause of methemoglobinemia was 20% benzocaine spray used for
      local anesthesia before intubation. Acutely developing methemoglobinemia is
      infrequently encountered in clinical practice. When confronted with cyanosis in
      the absence of cardiac or pulmonary disease, one must seriously consider the
      diagnosis of methemoglobinemia. The etiology of methemoglobinemia, the causative
      agents, the diagnosis, and the emergency treatment required are discussed.

PMID- 16596915
TI  - A busy practitioner's approach to evidence-based practice.

PMID- 16596914
TI  - Drug therapy in dental practice: nonopioid and opioid analgesics.
AB  - To prevent patient pain, the clinician may chose from opioid and nonopioid
      analgesics. It is rational for the practitioner to combine drugs from these
      classes when managing moderate to severe pain. To select combination regimens
      wisely, it is necessary to understand the significant pharmacological features of
      each category alone. Careful selection of an effective analgesic regimen based on
      the type and amount of pain the patient is expected to have can prevent the
      stress and anxiety associated with breakthrough pain. The clinician can and
      should develop a variety of effective, safe analgesic regimens, based on
      estimates of anticipated pain intensity that use sound pharmacological
      principles.

PMID- 16596916
TI  - Community participation following cerebrovascular accident: impact of the
      buffering model of social support.
AB  - This study examined data of older adults who had sustained a stroke and their
      ability to participate in the community following rehabilitation. There were 95
      participants in this study to determine the interaction effect of functional
      limitation and social support on community participation. The findings indicate
      that for people who had sustained a cerebrovascular accident, community
      participation was more related to their ability to do for themselves, rather than
      the support that was available to them. The implications of these findings for
      future practice, programs, and research are discussed.

PMID- 16596917
TI  - Coping during inpatient stroke rehabilitation: an exploratory study.
AB  - The emotional impact of surviving a stroke has not received the same attention as
      physical aspects. This is particularly true regarding how stroke survivors cope
      during inpatient rehabilitation. This study examined the coping strategies used
      by stroke survivors undergoing inpatient rehabilitation and the relationships
      between demographic or clinical variables and coping behaviors. This case series
      examined 16 acute stroke survivors via standardized assessments and a medical
      records review completed during the first week of inpatient rehabilitation.
      Stroke survivors used combinations of multiple coping strategies. All stroke
      survivors used a higher number and frequency of adaptive rather than maladaptive
      strategies. Women used a higher number of adaptive strategies. Stroke survivors
      with depression used maladaptive coping strategies more frequently, whereas those
      presenting with a greater number and severity of comorbidities used adaptive
      coping strategies more frequently. Stroke survivors with higher levels of coping
      self-efficacy used the strategies of active coping and positive reframing more
      frequently. Based on these results, it is recommended direct-care providers place
      greater emphasis on objectifying the emotional consequences of stroke. Further
      research is recommended regarding understanding the relationship between coping
      and outcomes.

PMID- 16596919
TI  - Enhancing research utilization capacity through multifaceted professional
      development.
AB  - Some occupational therapists report that they do not feel adequately prepared to
      perform the arduous tasks involved in integrating research into their practice.
      To explore how research utilization can be conducted by practicing clinicians,
      self-reported research utilization behaviors of a sample of 11 occupational
      therapists practicing in adult stroke rehabilitation were analyzed. The constant
      comparison of the interview data revealed that participants' clinical
      experiences, engagement in continuing education, involvement in research
      activities, and their mentoring of students contributed to their capacity to
      translate research evidence into practice. The results of the study suggest a
      model for enhancing research utilization capacity through professional
      development. Implications for practitioners, provider organizations, educators,
      and regulators of occupational therapy are discussed.

PMID- 16596918
TI  - Self-speech-induced facilitation of simple reaching movements in persons with
      stroke.
AB  - OBJECTIVE: Occupational therapists are routinely involved in upper-extremity
      rehabilitation in persons with stroke. Recently we have reported that self-speech
      can be used to facilitate simple reach in young and older adults. The purpose of
      this study is to examine whether self-speech-induced facilitation of simple reach
      can be translated in persons with stroke. METHOD: Following a counterbalanced
      repeated-measure design, seven persons with right brain stroke performed reaching
      and placing a glass on a cabinet shelf under four concurrent speech conditions of
      vocalizing the word "yeah" with both hemiplegic and nonhemiplegic sides. These
      four conditions are self-vocalization, external vocalization, imaginary
      vocalization, and no vocalization. Consistent with our previous study, in this
      study we also recorded the movement kinematics of angular movement of the upper
      arm. RESULTS: Reaching velocity was significantly higher under self-vocalization
      conditions compared to the reaching velocity under no vocalization or other
      vocalization conditions (p < .05). Motor performance in terms of velocity,
      nonhemiparetic side was significantly better than hemiparetic side (p < .05).
      CONCLUSION: The results suggest that self-speech can be used in facilitating
      movements in patients with stroke. When working with patients with right
      hemispheric stroke, therapists might explore possibilities of using patient's
      self-speech to enhance the quality of movement performance.

PMID- 16596920
TI  - Rehabilitation Medicine Summit: Building Research Capacity: executive summary.
AB  - The general objective of the "Rehabilitation Medicine Summit: Building Research
      Capacity" was to advance and promote research in medical rehabilitation by making
      recommendations to expand research capacity. The five elements of research
      capacity that guided the discussions were: (1) researchers; (2) research culture,
      environment, and infrastructure; (3) funding; (4) partnerships; and (5) metrics.
      The 100 participants included representatives of professional organizations,
      consumer groups, academic departments, researchers, governmental funding
      agencies, and the private sector. The small group discussions and plenary
      sessions generated an array of problems, possible solutions, and recommended
      actions. A post-Summit, multi-organizational initiative is called to pursue the
      agendas outlined in this report.

PMID- 16596921
TI  - Factors affecting patient recruitment in an acute rehabilitation randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate factors associated with randomized controlled trial
      patient recruitment by therapists. METHOD: Survey of 18 (of a possible 26)
      therapists who had agreed to recruit patients for a randomized controlled trial
      (78% response rate). RESULTS: Sixteen respondents had enrolled at least one
      patient. The site at which the therapist worked neither influenced the likelihood
      that a therapist would contact the researcher nor influenced the recruitment
      rate. Seventeen respondents reported that they contacted the researcher to
      discuss one or more of their patients for potential inclusion in the trial.
      Factors reported by therapists as reasons why they did not recommend the trial to
      eligible patients were not specific to study inclusion or exclusion criteria,
      rather were linked to personal judgments about patient suitability for the study.
      Regression analysis indicated that being enrolled or having completed master's
      level postgraduate studies, and choosing not to refer patients because of concern
      for their poor medical prognosis were the only factors that significantly
      influenced recruitment rate (p < 0.001). CONCLUSION: Recruitment practices vary
      amongst therapists. Selection of therapists with postgraduate qualifications as
      recruiters may be an effective way to enhance recruitment rate.

PMID- 16596922
TI  - The measurement properties and factor structure of the Test of Visual-Perceptual
      Skills-Revised: implications for occupational therapy assessment and practice.
AB  - OBJECTIVES: The aim of this study was to examine the measurement properties of
      the Test of Visual-Perceptual Skills-Revised (TVPS-R). METHODS: A group of 356
      typically developing children 5-11 years of age completed the TVPS-R along with
      three criterion measures. RESULTS: Several of the TVPS-R items had item-total
      subscale correlation coefficients were lower than the 0.20 correlation criteria.
      Cronbach's alpha coefficients varied between 0.74 and 0.84 for the seven
      subscales. The perceptual quotient (PQ) reliability coefficient for the age
      levels ranged between 0.79 and 0.91. The PQ total group reliability coefficient
      was 0.96. Results from the principal component analysis indicated that the
      majority of the TVPS-R items loaded on a dominant first factor. Confirmatory
      factor analytic models were assessed using four different goodness-of-fit
      indices. Two of the fit indices supported the unidimensional assumption (RMR and
      CFI ), while two of the fit indices did not support the TVPS-R one-factor model
      (chi-square and RMSEA). A unitary motor-free visual-perceptual factor was not
      found. CONCLUSION: The TVPS-R PQ should not be used as an overall performance
      summary score. Of the seven TVPS-R subscales, five can be used with confidence
      (visual discrimination, visual-spatial relationships, visual-sequential memory,
      visual figure ground, and visual-closure) whereas the visual memory and visual
      form constancy [corrected] subscales are not recommended.

PMID- 16596924
TI  - Examination of the Perceived Efficacy and Goal Setting System (PEGS) with
      children with disabilities, their parents, and teachers.
AB  - The Perceived Efficacy and Goal Setting System (PEGS) is an instrument and a
      process that enables children with disabilities to reflect on their ability to
      perform everyday occupations and to identify goals for occupational therapy
      intervention. In this study, 117 children with disabilities in grades 1-3
      completed the PEGS with occupational therapists who work in school settings.
      Children from 6-9 years of age with a variety of disabilities were able to self
      report perceptions of their effectiveness performing 24 activities that would be
      expected of them each day. Parents and teachers, who completed a parallel
      questionnaire, rated their abilities lower than the children did. The School
      Function Assessment, a measure of the amount and type of support required for
      school participation, had low correlations with the Parent and Teacher PEGS
      questionnaires and did not correlate with the Child PEGS. No differences in
      perceived efficacy were found for children across grades or gender; however,
      differences were found across types of disabilities. Children were able to use
      the perceived efficacy information to identify and prioritize goals for
      intervention and these goals remained stable 2 weeks later. Occupational
      therapists can use the PEGS within a client-centered practice to help the child
      set goals for therapy and to incorporate explicitly the perspectives of parents
      and teachers.

PMID- 16596923
TI  - Time use of mothers with school-age children: a continuing impact of a child's
      disability.
AB  - OBJECTIVE: The purpose of this study was to compare the time use of mothers of
      children with disabilities with the time use of mothers of children without
      disabilities. METHOD: Sixty mothers with children 3 to 14 years of age (30
      mothers with children with disabilities and 30 mothers with children without
      disabilities) completed time diaries over seven 24-hour days. RESULTS:
      Significant differences were found between the two groups when comparing mean
      hours spent per week by mothers in occupations involving child-care activities
      and recreational activities. Mothers of children with disabilities spent
      significantly more time in child-care activities and significantly less time in
      recreational activities. In addition, mothers of children with disabilities
      reported fewer typical days and rated the quality of days as poorer. As children
      got older, the gap between the time mothers devoted to child care increased
      between the two groups. CONCLUSION: The type of occupations a mother participates
      in varies significantly dependent upon whether a child in the family has a
      disability and the age of the child. Professionals need to work collaboratively
      with families to assist parents to meet the family's daily needs particularly in
      light of the time demands of the mother.

PMID- 16596925
TI  - A comparison of visual-perceptual and visual-motor skills between Palestinian and
      Israeli children.
AB  - PURPOSE: This pioneer study examines the visual-motor and visual-perceptual
      performance of Israeli and Palestinian children, and makes comparisons among
      these respective populations according to age, place of residence, and parental
      education. In addition, the study evaluates the validity of standardized
      assessment tools for use with Palestinian children, with the view of establishing
      a sound assessment battery for this underserved population. METHODS: Participants
      included 101 Israeli and 125 Palestinian children from kindergarten, first grade,
      and second grade who underwent visual-motor and visual-perceptual tests. RESULTS:
      Significant differences were found between the two cultural groups in all
      assessments. Results also refer to grade, place of residence, and parents'
      education variables. CONCLUSIONS: Although culture influences children's
      performance, children from different societies should be screened and, when
      necessary, evaluated and treated in order to enable their optimal functioning at
      school. The validity of the assessment tools used, expressed in the ability to
      differentiate between Israeli and Palestinian children, should be further studied
      in order to suggest that these assessments may be considered as part of an
      evaluation battery for determining the school readiness and ability to advance in
      grade level among Palestinian children.

PMID- 16596926
TI  - Evaluating the quality of reporting occupational therapy randomized controlled
      trials by expanding the CONSORT criteria.
AB  - CONTEXT: Well-reported randomized controlled trials (RCTs) are necessary for
      evidenced-based practice in the field of occupational therapy. OBJECTIVE: The
      primary purpose of this study was to analyze the quality of reporting in selected
      RCTs relevant to occupational therapy by using the Nelson-Moberg Expanded CONSORT
      Instrument (NMECI). The interrater reliability of the NMECI was also tested.
      METHOD: The 201-sub-item NMECI was developed by the authors to clarify the 22
      item CONSORT Statement, each item of which raises several issues. Fourteen RCTs
      obtained through the OTseeker database were analyzed independently by the
      authors. RESULTS: The 14 articles complied with slightly more than half of the
      sub-items of the NMECI (M = 104.2, SD = 32.9 for the main rater). The only area
      of full compliance involved reporting of objectives and hypotheses; areas of
      frequent noncompliance included reporting of adverse events, randomization, and
      blinding. The intraclass correlation coefficient assessing level of interrater
      agreement on the total NMECI score was .95, indicating strong agreement overall.
      For the 176 kappas that could be computed on individual sub-items, the median
      kappa was .85, with an inter-quartile range from .58 to 1, indicating high levels
      of agreement for most items. However, 29 kappas fell below the moderate level of
      agreement (.40). CONCLUSIONS: The field of occupational therapy needs increased
      sophistication in conducting and reporting RCTs. The NMECI shows promise in
      evaluating the quality of RCTs, given refinements to some items.

PMID- 16596928
TI  - Chemical imbalance or moral weakness? Personal responsibility in a time of brain
      science.

PMID- 16596927
TI  - Occupations: strands of coherence in a life.

PMID- 16596929
TI  - A bat out of hell.

PMID- 16596930
TI  - Sleep and ADHD: a review.

PMID- 16596931
TI  - Sleep in children with developmental disabilities.
AB  - Sleep disturbances are more common in children and adolescents with developmental
      disabilities than in non-disabled individuals. Given the potential benefit of
      improved sleep for a patient's daytime functioning, it is important that
      clinicians who work with this population query caretakers about sleep problems
      and offer intervention, whether behavioral or pharmacological. Sleep problems in
      children with developmental disorders often fail to improve spontaneously, as may
      be the case in typically developing children, which can lead to further distress,
      disappointment, and frustration for families. Attempting to resolve sleep
      difficulties as they arise can benefit not only the patient, but also the
      patient's caretakers.

PMID- 16596932
TI  - Behavioral and massage treatments for infant sleep problems.

PMID- 16596933
TI  - Sleep in medically compromised children.

PMID- 16596934
TI  - Obstructive sleep apnea syndrome: clinical features in children vs. adults.

PMID- 16596935
TI  - Intrahepatic calculi.

PMID- 16596936
TI  - Utilization of Connecticut and Massachusetts hospitals by Rhode Island residents,
      1997-2003.

PMID- 16596938
TI  - A collaborative management model for mental health care at the Rhode Island Free
      Clinic.

PMID- 16596937
TI  - Olive oil in the treatment of hypercholesterolemia.
AB  - Olive oil consumption increases HDL-cholesterol levels, while decreasing LDL
      cholesterol levels, LDL susceptibility to oxidation and lipid peroxidation. The
      reduction of cellular oxidative stress, thrombogenicity and the formation of
      atheroma plague can explain the preventive effects of olive oil on
      atherosclerosis development. In addition to reducing risk factors for coronary
      heart disease, olive oil might also help prevent certain types of cancers, and
      beneficially modify immune and inflammatory responses.

PMID- 16596939
TI  - A skeletal etymology, part I.

PMID- 16596940
TI  - Quantitative trait nucleotide analysis using Bayesian model selection.
AB  - Although much attention has been given to statistical genetic methods for the
      initial localization and fine mapping of quantitative trait loci (QTLs), little
      methodological work has been done to date on the problem of statistically
      identifying the most likely functional polymorphisms using sequence data. In this
      paper we provide a general statistical genetic framework, called Bayesian
      quantitative trait nucleotide (BQTN) analysis, for assessing the likely
      functional status of genetic variants. The approach requires the initial
      enumeration of all genetic variants in a set of resequenced individuals. These
      polymorphisms are then typed in a large number of individuals (potentially in
      families), and marker variation is related to quantitative phenotypic variation
      using Bayesian model selection and averaging. For each sequence variant a
      posterior probability of effect is obtained and can be used to prioritize
      additional molecular functional experiments. An example of this quantitative
      nucleotide analysis is provided using the GAW12 simulated data. The results show
      that the BQTN method may be useful for choosing the most likely functional
      variants within a gene (or set of genes). We also include instructions on how to
      use our computer program, SOLAR, for association analysis and BQTN analysis.

PMID- 16596941
TI  - The F7 gene and clotting factor VII levels: dissection of a human quantitative
      trait locus.
AB  - Localization of human quantitative trait loci (QTLs) is now routine. However,
      identifying their functional DNA variants is still a formidable challenge. We
      present a complete dissection of a human QTL using novel statistical techniques
      to infer the most likely functional polymorphisms of a QTL that influence plasma
      levels of clotting factor VII (FVII), a risk factor for cardiovascular disease.
      Resequencing of 15 kb in and around the F7 gene identified 49 polymorphisms,
      which were then genotyped in 398 people. Using a Bayesian quantitative trait
      nucleotide (BQTN) method, we identified four to seven functional variants that
      completely account for this QTL. These variants include both rare coding variants
      and more common, potentially regulatory polymorphisms in intronic and promoter
      regions.

PMID- 16596942
TI  - Identification of spatial genetic boundaries using a multifractal model in human
      population genetics.
AB  - There are two purposes in displaying spatial genetic structure. One is that a
      visual representation of the variation of the genetic variable should be provided
      in the contour map. The other is that spatial genetic structure should be
      reflected by the patterns or the gradients with genetic boundaries in the map.
      Nevertheless, most conventional interpolation methods, such as Cavalli-Sforza's
      method in genography, inverse distance-weighted methods, and the Kriging
      technique, focus only on the first primary purpose because of their arbitrary
      thresholds marked on the maps. In this paper we present an application of the
      contour area multifractal model (CAMM) to human population genetics. The method
      enables the analysis of the geographic distribution of a genetic marker and
      provides an insight into the spatial and geometric properties of obtained
      patterns. Furthermore, the CAMM may overcome some of the limitations of other
      interpolation techniques because no arbitrary thresholds are necessary in the
      computation of genetic boundaries. The CAMM is built by establishing power law
      relationships between the area A (> or =rho) in the contour map and the value p
      itself after plotting these values on a log-log graph. A series of straight-line
      segments can be fitted to the points on the log-log graph, each representing a
      power law relationship between the area A (> or =rho) and the cutoff genetic
      variable value for rho in a particular range. These straight-line segments can
      yield a group of cutoff values, which can be identified as the genetic boundaries
      that can classify the map of genetic variable into discrete genetic zones. These
      genetic zones usually correspond to spatial genetic structure on the landscape.
      To provide a better understanding of the interest in the CAMM approach, we
      analyze the spatial genetic structures of three loci (ABO, HLA-A, and TPOX) in
      China using the CAMM. Each synthetic principal component (SPC) contour map of the
      three loci is created by using both Han and minority groups data together. These
      contour maps all present an obvious geographic diversity, which gradually
      increases from north to south, and show that the genetic differences among
      populations in different districts of the same nationality are greater than those
      among different nationalities of the same district. It is surprising to find that
      both the value of p and the fractal dimension alpha have a clear north to south
      gradient for each locus, and the same clear boundary between southern and
      northern Asians in each contour map is still seen in the zone of the Yangtze
      River, although substantial population migrations have occurred because of war or
      famine in the last 2,000 or 3,000 years. A clear genetic boundary between
      Europeans and Asians in each contour map is still seen in northwestern China with
      a small value of alpha, although the genetic gradient caused by gene flow between
      Europeans and Asians has tended to show expansion from northwestern China. From
      the three contour maps another interesting result can be found: The values of
      alpha north of the Yangtze River are generally less than those south of the
      Yangtze River. This indicates that the genetic differences among the populations
      north of the Yangtze River are generally smaller than those in populations south
      of the Yangtze River.

PMID- 16596943
TI  - The Basques: review of population genetics and Mendelian disorders.
AB  - The Basques live at the western end of the Pyrenees along the Atlantic Ocean and
      are thought to represent the descendants of a pre-Neolithic people. They
      demonstrate marked specificities regarding language and genetics among the
      European populations. We review the published data on the population genetics and
      Mendelian disorders of the Basques. An atypical distribution in some blood group
      polymorphisms (ABO, Rhesus, and Duffy) was first found in this population.
      Subsequently, additional characteristics have been described with regard to
      proteins (enzymes and immunoglobulins) and the HLA system. The advent of
      molecular biology methods in the 1990s allowed further insights into Basque
      population genetics based mainly on Y-chromosome and mitochondrial DNA. In
      addition, the Basques demonstrate peculiarities regarding the distribution of
      various inherited diseases (i.e., unusual frequencies or founding effects). Taken
      together, these data support the idea of an ancient and still relatively unmixed
      population subjected to genetic drift.

PMID- 16596944
TI  - Mitochondrial DNA of ancient Cumanians: culturally Asian steppe nomadic
      immigrants with substantially more western Eurasian mitochondrial DNA lineages.
AB  - The Cumanians were originally Asian pastoral nomads who in the 13th century
      migrated to Hungary. We have examined mitochondrial DNA from members of the
      earliest Cumanian population in Hungary from two archeologically well-documented
      excavations and from 74 modern Hungarians from different rural locations in
      Hungary. Haplogroups were defined based on HVS I sequences and examinations of
      haplogroup-associated polymorphic sites of the protein coding region and of HVS
      II. To exclude contamination, some ancient DNA samples were cloned. A database
      was created from previously published mtDNA HVS I sequences (representing 2,615
      individuals from different Asian and European populations) and 74 modem Hungarian
      sequences from the present study. This database was used to determine the
      relationships between the ancient Cumanians, modern Hungarians, and Eurasian
      populations and to estimate the genetic distances between these populations. We
      attempted to deduce the genetic trace of the migration of Cumanians. This study
      is the first ancient DNA characterization of an eastern pastoral nomad population
      that migrated into Europe. The results indicate that, while still possessing a
      Central Asian steppe culture, the Cumanians received a large admixture of
      maternal genes from more westerly populations before arriving in Hungary. A
      similar dilution of genetic, but not cultural, factors may have accompanied the
      settlement of other Asian nomads in Europe.

PMID- 16596945
TI  - Screening of APOB gene mutations in subjects with clinical diagnosis of familial
      hypercholesterolemia.
AB  - Monogenic hypercholesterolemia is a group of lipid disorders, most of which have
      autosomal dominant transmission. Familial defective apoB (FDB) resulting from
      mutations in the APOB gene is a well-recognized cause of autosomal dominant
      monogenic hypercholesterolemia (ADMH). However, the frequency of FDB among
      patients with ADMH is not well established. The aim of our research was to screen
      for mutations responsible for FDB in subjects with a clinical diagnosis of
      familial hypercholesterolemia. We studied 408 patients from the Spanish Register
      of Familial Hypercholesterolemia, proportionally distributed among all Spanish
      regions. Abnormal SSCP patterns of the APOB gene were checked by DNA sequencing
      and restriction analysis. Three out of the 408 patients were carriers of the
      R3500Q mutation, and 2 subjects were carriers of the silent T3552T mutation; in
      both of these patients functional mutations in the LDL receptor gene were found.
      We conclude that FDB is not a common cause of ADMH in Spain; the R3500Q mutation
      is the only mutation in APOB causing FDB, and the LDL receptor binding domain of
      APOB is highly conserved in the studied sample.

PMID- 16596946
TI  - Polymorphic Alu insertions and genetic diversity among African populations.
AB  - Thorough assessment of modern genetic diversity and interpopulation affinities
      within the African continent is essential for understanding the processes that
      have been at work during the course of worldwide human evolution. Regardless of
      whether autosomal, Y-chromosome, or mtDNA markers are used, allele- or haplotype
      frequency data from African populations are necessary in setting the framework
      for the construction of global population phylogenies. In the present study we
      analyze genetic differentiation and population structure in a data set of nine
      African populations using 12 polymorphic Alu insertions (PAls). Furthermore, to
      place our findings within a global context, we also examined an equal number of
      non-African groups. Frequency data from 456 individuals presented for the first
      time in this work plus additional data obtained from the literature indicate an
      overall pattern of higher intrapopulation diversity in sub-Saharan populations
      than in northern Africa, a prominent differentiation between these two locations,
      an appreciably high degree of transcontinental admixture in Egypt, and
      significant discontinuity between Morocco and the Iberian peninsula. Moreover,
      the topologies of our phylogenetic analyses suggest that out of the studied sub
      Saharan groups, the southern Bantu population of Sotho/ Tswana presents the
      highest level of antiquity, perhaps as a result of ancestral or acquired Khoisan
      genetic signals. Close affinities of eastern sub-Saharan populations with Egypt
      in the phylogenetic trees may indicate the existence of gene flow along the Nile
      River.

PMID- 16596947
TI  - Spectrum of CFTR mutations on Reunion Island: impact on neonatal screening.
AB  - The large heterogeneity in the cystic fibrosis (CF) gene is the main difficulty
      for genotype characterization. Numerous studies have reported considerable
      variations in frequencies of CF transmembrane conductance regulator (CFTR)
      mutations in different populations, such as African, Asian, or European
      populations. To completely characterize the spectrum of mutations in the CFTR
      gene in the Reunion Island population, we screened 228 CF chromosomes using
      denaturing high-pressure liquid chromatography and denaturing gradient gel
      electrophoresis following by direct sequencing. We identified 27 mutations,
      accounting for 93% of CF chromosomes. They included three novel mutations (M1T,
      3121-3C-->G, and L1324P), which are described in this paper. The detection of
      such a high proportion of Reunion Island CFTR mutations is important for
      improving neonatal screening of CF on Reunion Island.

PMID- 16596948
TI  - Morphological and molecular systematics of Rocky Mountain alpine Laccaria.
AB  - The alpine zone is comprised of habitats at elevations above treeline, and
      macromycetes play important ecological roles as decomposers and mycorrhizal
      symbionts here as elsewhere. Laccaria is an important group of ectomycorrhizal
      basidiomycetes widely used in experimental and applied research. A systematic
      study of alpine Laccaria species using morphological, cultural and molecular
      (ribosomal DNA internal transcribed spacer) data revealed five taxa in the Rocky
      Mountain alpine zone: L. laccata var. pallidifolia, L. nobilis (the first
      published report for arctic-alpine habitats), L. pumila, L. montana and L.
      pseudomontana (a newly described taxon similar to L. montana with more
      ellipsoidal, finely echinulate basidiospores). All occur in the southern Rocky
      Mountains of Colorado; however, only L. pumila and L. montana were found on the
      Beartooth Plateau in the northern Rocky Mountains of Montana and Wyoming. All are
      associated with dwarf and shrub Salix species, with L. laccata var. pallidifolia
      also associated with Dryas octopetala and Betula glandulosa. Maximum-parsimony
      phylogenetic analysis of rDNA-ITS sequences for 27 Laccaria accessions supports
      the morphological species delineations.

PMID- 16596950
TI  - Effects of elevation, slope position and livestock exclusion on microfungi
      isolated from soils of Mediterranean grasslands.
AB  - The fungal communities of grassland soils in Spain from four sites at different
      elevations were studied. Each site contained grazed and fenced ungrazed plots.
      These plots were situated in two slope positions (upper and lower zones). The
      ungrazed plots, fenced off 6 y before the sampling, were part of a study of
      global change that simulates conditions of rural abandonment, which is widespread
      in Iberian countries, since Spain joined the European Union. We analyzed the
      structure of the soil fungi communities and its relationship with herbaceous
      vegetation. The distribution of 207 taxa of fungi revealed that the elevation was
      the main factor of fungal variability; the effect of grazing and slope position
      were associated with less variability. Although a halt in grazing resulted in the
      accumulation of standing plants and plant litter in these ecosystems, it had
      relatively little effect on soil microfungi and appeared to be related mainly to
      growing conditions affected by that accumulation.

PMID- 16596949
TI  - Molecular defense systems are expressed in the king bolete (Boletus edulis)
      growing near metal smelters.
AB  - The induction of defense systems against metal exposure was investigated in 48
      wild-growing fruiting bodies of the king bolete (Boletus edulis) from two areas
      polluted with several transition metals from smelters, as well as five reference
      areas. To determine the degree of metal exposure, cadmium (Cd), zinc (Zn), and
      copper (Cu) were determined in caps of fruiting bodies by atomic absorption
      spectrophotometry (AAS), whereas mercury (Hg) was determined by cold vapor atomic
      fluorescence spectrometry (CVAFS). Caps were analyzed further with respect to
      relative activities of the antioxidant enzymes, superoxide dismutase (SOD) and
      catalase (CAT), as well as concentrations of total glutathione (GSHTOT = GSH +
      GSSG) and relative concentrations of heat shock protein 70 kDa (HSP70). The
      results showed that concentrations of the four metals, as well as SOD, CAT and
      HSP70, were significantly elevated in the exposed group (Mann-Whitney, P < or =
      0.001). In contrast, GSHTOT was significantly lowered in the exposed group (P <
      or = 0.05). Significant positive correlations were established between
      concentrations of Cd, Zn, Hg, or Cu and activities of SOD (Spearman's P < or =
      0.01 for the association between SOD and Cd, P < or = 0.001 for all other metal
      exposure parameters), CAT (P < or = 0.001 for all exposure parameters), or
      expression of HSP70 (P < or = 0.001 for all exposure parameters). Significant
      negative correlations were found between total GSH and Cd (P < or = 0.001), Zn (P
      < or = 0.001), or Hg (P < or = 0.05). We conclude that antioxidant enzymes are
      induced in wild-growing B. edulis exposed to environmentally relevant
      concentrations of potentially toxic transition metals; whereas the net
      consumption of GSH that occurs with increasing metal exposure may reflect GSH
      consumption by mechanisms of metal detoxification. Finally, the induction of
      HSP70 suggests that the antioxidant response and the mechanisms in which GSH is
      consumed are insufficient for protection against the harmful effects of severe
      metal stress.

PMID- 16596951
TI  - Density-dependent insect-mold interactions: effects on fungal growth and spore
      production.
AB  - Larvae of saprophagous insects often have been suspected of being competitors of
      filamentous fungi on decaying organic matter, which negatively influence mold
      development. Of interest, the role of insects in determining fungal growth and
      the onset of sporulation largely has been ignored. I used Aspergillus niger and
      the vinegar fly Drosophila melanogaster as an ecological model system to analyze
      the influence of insect larvae on daily fungal growth and the start of
      conidiospore production. I used an artificial substrate to test whether the
      effect of larval density (one, five and 10 larvae) and inoculation date of the
      mold (2 and 3 d ahead of the addition of larvae) significantly altered fungal
      growth. Fungal growth (area covered by hyphal tissue of the artificial patch) was
      affected negatively by the number of larvae and by the time that elapsed between
      inoculation with fungal spores and transfer of larvae to the patches. Whereas one
      larva had only a minor effect on fungal growth, five or 10 larvae strongly
      hampered mold development. As time between inoculation with spores and
      introduction of fly larvae increased, mold increased, indicating a priority
      effect for the fungus. When 10 larvae were transferred at the same time as the
      patches were inoculated with spores, almost no mold was visible within the period
      of observation (after 12 d). In comparison with control treatment (no insect
      larvae), an increase in larval density caused an increasing delay of several days
      in the start of spore production. Thus only minor changes in the density of
      insect larvae and the time that larvae entered the patches after inoculation with
      spores had an enormous effect on fungal growth and spore production. Therefore
      insects co-occurring with mold on ephemeral resources might constitute an
      important biotic factor driving local fungal population dynamics. The mechanisms
      leading to the suppression of fungal growth and the evolutionary implications of
      insect-mold interactions are discussed.

PMID- 16596952
TI  - Molecular and morphological characterization of Pyricularia and allied genera.
AB  - The phylogenetic relationships of Pyricularia species and species from related
      genera were established from sequences of the internal transcribed spacer
      ribosomal RNA gene. Phylogenetic analysis disclosed a consistent correlation with
      spore morphology. Most Pyricularia species studied, and two species of Dactylaria
      that have obpyriform conidia, fell within the Magnaporthaceae cluster with high
      bootstrap support. Pyricularia variabilis was more related to Dactylaria,
      Tumularia or Ochroconis species than to the Magnaporthaceae. Dactylaria and
      species of Nakataea, Ochroconis, Pyriculariopsis and Tumularia were distinct from
      the Magnaporthaceae, and the genus Dactylaria is polyphyletic. The combination of
      morphological and molecular characters, such as spore morphology and ITS
      ribosomal DNA sequences data, suggested that conidial shape could be a primary
      character to distinguish Pyricularia from related genera.

PMID- 16596953
TI  - The causal agents of witches' broom and frosty pod rot of cacao (chocolate,
      Theobroma cacao) form a new lineage of Marasmiaceae.
AB  - The two most devastating diseases of cacao (Theobroma cacao)--the source of
      chocolate--in tropical America are caused by the fungi Crinipellis perniciosa
      (witches' broom disease) and Moniliophthora roreri (frosty pod rot or moniliasis
      disease). Despite the agricultural, socio-economic and environmental impact of
      these fungi, most aspects of their life cycles are unknown, and the phylogenetic
      relationships of M. roreri have yet to be conclusively established. In this
      paper, extensive phylogenetic analyses of five nuclear gene regions (28S rDNA,
      18S rDNA, ITS, RPB1, and EF1-alpha) confirm that C. perniciosa and M. roreri are
      sister taxa that belong in the Marasmiaceae (euagarics). Furthermore, these taxa
      form part of a separate and distinct lineage within the family. This lineage
      includes the biotrophic fungi Moniliophthora perniciosa comb. nov. and M. roreri,
      as well as one undescribed endophytic species. The sister genera to
      Moniliophthora are Marasmius, Crinipellis and Chaetocalathus, which consist
      mainly of saprotrophic litter fungi.

PMID- 16596954
TI  - Phylogenetic origins of two cleistothecial fungi, Orbicula parietina and
      Lasiobolidium orbiculoides, within the operculate discomycetes.
AB  - Parsimony, maximum-likelihood and Bayesian analyses of SSU rDNA sequences of
      representative taxa of Pezizomycetes, Eurotiomycetes, Dothideomycetes,
      Leotiomycetes and Sordariomycetes, all strongly support the cleistothecial fungi
      Orbicula parietina and Lasiobolidium orbiculoides to be of pezizalean origin.
      Previous hypotheses of close affinities with cleistothecial or highly reduced
      fungi now placed in the Thelebolales, Eurotiales or Onygenales are rejected.
      Orbicula parietina and L. orbiculoides are deeply nested within Pyronemataceae
      (which subsumes the families Ascodesmidaceae, Glaziellaceae and Otideaceae). LSU
      rDNA sequences suggest that Orbicula is nested within the apothecia-forming genus
      Pseudombrophila (including Nannfeldtiella and Fimaria) and that L. orbiculoides
      is closely related. Ascodesmis and Lasiobolus, which have been suggested as
      closely related to Orbicula and Lasiobolidium, are identified as a sister lineage
      to the Pseudombrophila lineage. Cleistothecial forms that have lost the ascus
      operculum and ability to discharge spores actively have evolved at least once in
      the Pseudombrophila lineage. Some species of Pseudombrophila produce subglobular
      ascomata initials that are closed early in development and open only in the mid
      mesohymenial phase. We hypothesize that, in the Pseudombrophila lineage, ascomata
      forms that never open are derived from ascomata that open late in development.
      The placement of O. parietina and L. orbiculoides within Pseudombrophila is
      supported by morphological characters, ecology and temperature optima for
      fruiting.

PMID- 16596955
TI  - Phylogenetics and evolution of nematode-trapping fungi (Orbiliales) estimated
      from nuclear and protein coding genes.
AB  - The systematic classification of nematode-trapping fungi is redefined based on
      phylogenies inferred from sequence analyses of 28S rDNA, 5.8S rDNA and beta
      tubulin genes. Molecular data were analyzed with maximum parsimony, maximum
      likelihood and Bayesian analysis. An emended generic concept of nematode-trapping
      fungi is provided. Arthrobotrys is characterized by adhesive networks,
      Dactylellina by adhesive knobs, and Drechslerella by constricting-rings.
      Phylogenetic placement of taxa characterized by stalked adhesive knobs and non
      constricting rings also is confirmed in Dactylellina. Species that produce
      unstalked adhesive knobs that grow out to form loops are transferred from
      Gamsylella to Dactylellina, and those that produce unstalked adhesive knobs that
      grow out to form networks are transferred from Gamsylella to Arthrobotrys.
      Gamsylella as currently circumscribed cannot be treated as a valid genus. A
      hypothesis for the evolution of trapping-devices is presented based on multiple
      gene data and morphological studies. Predatory and nonpredatory fungi appear to
      have been derived from nonpredatory members of Orbilia. The adhesive knob is
      considered to be the ancestral type of trapping device from which constricting
      rings and networks were derived via two pathways. In the first pathway adhesive
      knobs retained their adhesive material forming simple two-dimension networks,
      eventually forming complex three-dimension networks. In the second pathway
      adhesive knobs lost their adhesive materials, with their ends meeting to form
      nonconstricting rings and they in turn formed constricting rings with three
      inflated-cells.

PMID- 16596956
TI  - Anatomical and molecular characterization of Lactarius aff. omphaliformis,
      Russula alnijorullensis and Cortinarius tucumanensis ectomycorrhizae on Alnus
      acuminata.
AB  - Ectomycorrhizae (ECM) of Lactarius aff. omphaliformis Romagn., Russula
      alnijorullensis (Sing.) Sing. and Cortinarius tucumanensis Mos. on Andean alder
      (Alnus acuminata Kunth) were characterized and identified. The identification of
      the fungal symbionts was achieved by morpho-anatomical observations of
      mycorrhizae and by comparison of ITS-RFLP patterns obtained from ECM and
      fruitbodies. L. aff omphaliformis ECM differed in some morphological details such
      as ramification and mantle type from ECM of the same species on A. glutinosa. L.
      aff omphaliformis ECM show an orange to ochre mantle containing latex cells,
      which stain with sulpho-vanillin, emanating hyphae without clamps. R.
      alnijorullensis ECM represent a typical Russula-type-ECM, light yellow to
      pinkish, the outer mantle being composed of triangular latex-filled cells
      staining with sulpho-vanillin, emanating hyphae without clamps. C. tucumanensis
      ECM exhibit a white (silvery) to yellowish brown mantle covered with soil
      particles, emanating hyphae with clamps.

PMID- 16596957
TI  - Neonectria castaneicola and Neo. rugulosa in Japan.
AB  - Differences between Neonectria castaneicola, which causes stem and perennial
      canker of trees, and Neo. rugulosa have not been clearly shown in previous
      studies. In this study these two species were compared in detail using 17
      Japanese isolates consisting of 10 strains of Neo. castaneicola and seven of Neo.
      rugulosa. Four-spored asci were constantly found in Neo. castaneicola and this
      species produced larger ascospores and macroconidia than Neo. rugulosa which
      produced eight-spored asci. The mating system of Neo. castaneicola was
      homothallic while Neo. rugulosa was heterothallic. Characters in each species,
      such as the number of ascospores in an ascus and mating system, were constantly
      transferred to the 3rd generation. Molecular analysis revealed that the 10
      isolates of Neo. castaneicola and seven of Neo. rugulosa were differentiated
      using rDNA sequence data from the nuclear rDNA ITS region. Moreover, Neo.
      castaneicola and Neo. rugulosa were separated into different clades. From these
      results, it was concluded that Neo. castaneicola should be maintained as an
      independent species, separate from Neo. rugulosa. The isolates of Neo. rugulosa
      used in this study were the first reported in Japan and found on Castanea
      crenata, Castanopsis sp., Myrica rubra and Quercus acutissima.

PMID- 16596958
TI  - Phylogeny and taxonomy of the North American clade of the Ceratocystis fimbriata
      complex.
AB  - Ceratocystis fimbriata is a widely distributed, plant pathogenic fungus that
      causes wilts and cankers on many woody hosts. Earlier phylogenetic analyses of
      DNA sequences revealed three geographic clades within the C. fimbriata complex
      that are centered respectively in North America, Latin America and Asia. This
      study looked for cryptic species within the North American clade. The internal
      transcribed spacer regions (ITS) of the rDNA were sequenced, and phylogenetic
      analysis indicated that most isolates from the North American clade group into
      four host-associated lineages, referred to as the aspen, hickory, oak and cherry
      lineages, which were isolated primarily from wounds or diseased trees of Populus,
      Carya, Quercus and Prunus, respectively. A single isolate collected from P.
      serotina in Wisconsin had a unique ITS sequence. Allozyme electromorphs also were
      highly polymorphic within the North American clade, and the inferred phylogenies
      from these data were congruent with the ITS-rDNA analyses. In pairing experiments
      isolates from the aspen, hickory, oak and cherry lineages were interfertile only
      with other isolates from their respective lineages. Inoculation experiments with
      isolates of the four host-associated groupings showed strong host specialization
      by isolates from the aspen and hickory lineages on Populus tremuloides and Carya
      illinoensis, respectively, but isolates from the oak and cherry lineages did not
      consistently reveal host specialization. Morphological features distinguish
      isolates in the North American clade from those of the Latin American clade
      (including C. fimbriata sensu stricto). Based on the phylogenetic evidence,
      interfertility, host specialization and morphology, the oak and cherry lineages
      are recognized as the earlier described C. variospora, the poplar lineage as C.
      populicola sp. nov., and the hickory lineage as C. caryae sp. nov. A new species
      associated with the bark beetle Scolytus quadrispinosus on Carya is closely
      related to C. caryae and is described as C. smalleyi.

PMID- 16596959
TI  - Development of an isolate-specific marker for tracking Phaeomoniella
      chlamydospora infection in grapevines.
AB  - Petri disease causes decline of grapevines worldwide. The grapevine endophyte
      Phaeomoniella chlamydospora is the most important fungal pathogen associated with
      this disease. Epidemiological studies of this pathogen have been hampered by its
      common occurrence in the internal tissue of apparently healthy vines. Development
      of a molecular marker for a single strain would overcome this limitation and aid
      experiments designed to answer key questions about the biology of this pathogen.
      Genetic variation analysis of New Zealand and Italian strains of P. chlamydospora
      detected a potential molecular marker in New Zealand isolate A21.
      Characterization of the 1010 bp marker band showed that it had 50% identity to
      moxY, a gene involved in the aflatoxin biosynthetic pathway of Aspergillus
      parasiticus. Sequencing of the region flanking the 1010 bp product revealed a
      single nucleotide polymorphism in the 3' border of the marker band. Primers were
      designed to amplify a 488 bp fragment encompassing this polymorphic site and
      cleavage of this product with the restriction enzyme BsrI produced three bands
      only in isolate A21 and two bands in all other isolates tested. The sensitivity
      of the PCR-RFLP protocol was increased with a nested PCR approach and the
      protocol optimized for soil and wood samples. When the nested PCR/RFLP procedure
      was used to determine the persistence of viable and nonviable spores in soil, the
      results showed that nonviable spores were undetected after 8 wk whereas viable
      spores still could be detected at 17 wk.

PMID- 16596960
TI  - Phylogeny of Rosellinia capetribulensis sp. nov. and its allies (Xylariaceae).
AB  - A new Rosellinia species, R. capetribulensis isolated from Calamus sp. in
      Australia is described. R. capetribulensis is characterized by perithecia
      immersed within a carbonaceous stroma surrounded by subiculum-like hyphae, asci
      with large, barrel-shaped amyloid apical apparatus and large dark brown spores.
      Morphologically, R. capetribulensis appears to be similar to R. bunodes, R.
      markhamiae and R. megalospora. To gain further insights into the phylogeny of
      this new taxon we analyzed the ITS-5.8S rDNA using maximum parsimony and
      likelihood methods. In addition, a morphological dataset also was analyzed
      phylogenetically to investigate possible affinities. ITS rDNA based phylogenies
      reveal that R. capetribulensis is closely related to other Rosellinia species
      showing closest affinity to R. arcuata, RL necatrix and R. pepo. However,
      analysis of R. capetribulensis forms an unsupported branch sister to these taxa.
      Results from the morphological matrix indicate a close morphological affinity to
      members of Rosellinia subgenus Rosellinia. Despite that ITS rDNA and
      morphological analyses present difficulties in constructing a proper phylogenetic
      framework among Rosellinia and allied genera, there is sufficient evidence to
      support the establishment of the new taxon in the genus Rosellinia. The
      morphological similarities and differences between R. capetribulensis and allied
      genera such as Astrocystis and Entoleuca are also briefly discussed.

PMID- 16596961
TI  - Botryosphaeria viticola sp. nov. on grapevines: a new species with a Dothiorella
      anamorph.
AB  - Botryosphaeria viticola sp. nov., isolated from pruned canes of Vitis vinifera in
      NE Spain, is described and illustrated. Phylogenetic analysis based on ITS and
      EF1-alpha sequences and morphological characters of both anamorph and teleomorph
      confirmed this taxon to be included within the group of Botryosphaeria species
      with Dothiorella anamorphs. It is related most closely to B. sarmentorum and B.
      iberica from which it differs in morphological characters of the teleomorph and
      DNA sequences.

PMID- 16596962
TI  - Cercosporella acroptili and Cercosporella centaureicola sp. nov.--potential
      biological control agents of Russian knapweed and yellow starthistle,
      respectively.
AB  - Russian knapweed (Acroptilon repens [L.] DC.) and yellow starthistle (Centaurea
      solstitialis L.) are invasive weeds in the western United States, and both weeds
      are targeted for biological control. Cercosporella acroptili (Bremer) U. Braun
      was identified as a possible biological control agent for A. repens, and a
      morphologically similar Cercosporella sp. recently was found damaging to C.
      solstitialis in the field. Because both fungi are potentially important for
      biological control of the respective weeds, studies were undertaken to ascertain
      whether the isolates were identical based on morphology, pathogenicity, growth
      and spore production, and genetics (molecular characterization of the internal
      transcribed spacer regions of the ribosomal RNA genes). Differences in these
      variables between the two isolates were sufficient to indicate that the isolate
      from C. solstitialis was distinct and justified a new description at the species
      level: Cercosporella centaureicola sp. nov.

PMID- 16596963
TI  - The genus Pyrenomyxa and its affinities to other cleistocarpous Hypoxyloideae as
      inferred from morphological and chemical traits.
AB  - Types and authentic specimens of Hypoxylon piceum, Pulveria porrecta, and
      Pyrenomyxa invocans were studied for morphological traits and extrolite (=
      secondary metabolite) profiles generated by analytical HPLC with UV-visual and
      mass spectrometric detection. The orange stromatal pigments of P. invocans are
      rubiginosin A and mitorubrinol. It lacks three different types of extrolites
      (BNT, macrocarpone and hypomiltin) that are known from Hypoxylon taxa and occur
      in H. piceum and P. porrecta. In agreement with morphological traits, the latter
      two names are regarded as synonymous and transferred to Pyrenomyxa. Another
      species from Eastern Russia, Pyrenomyxa morganii sp. nov., is recognized. It
      contains yet unidentified azaphilones besides BNT and orsellinic acid, and its
      culture produces 5-methylmellein and a virgariella-like anamorph. These findings
      suggest a close relationship of Pyrenomyxa to Hypoxylon and emphasize the utility
      of chemotaxonomic traits for fungal taxonomy in general. Pyrenomyxa is accepted
      ad interim until the phylogenetic relationships among Hypoxylon have been further
      evaluated by means of chemotaxonomic, morphological and molecular methods.

PMID- 16596964
TI  - A new poroid species of Resupinatus from Puerto Rico, with a reassessment of the
      cyphelloid genus Stigmatolemma.
AB  - A fungus with gelatinous poroid fruiting bodies was found in Puerto Rico and
      determined by macro- and micromorphology to be most similar to members of the
      lamellate agaric genus Resupinatus. This species is described as a new species,
      Resupinatus porosus. Phylogenetic analyses of ribosomal DNA sequences support the
      inclusion of this fungus in the clade containing Resupinatus, and indicate that
      this monophyletic group also includes members of Asterotus and the cyphelloid
      genus Stigmatolemma. Resupinatus porosus is another example of tropical poroid
      representatives of lamellate agaric genera. Resupinatus is emended to include
      species with poroid (R. porosus) or merulioid (R. merulioides) hymenophore as
      well as those with laterally stipitate (Asterotus) or cyphelloid (Stigmatolemma)
      fruiting bodies. Seven new combinations in Resupinatus are proposed to
      accommodate well-known species of Stigmatolemma.

PMID- 16596966
TI  - Relating behavior and neuroscience: introduction and synopsis.

PMID- 16596965
TI  - Development of ToxA and ToxB promoter-driven fluorescent protein expression
      vectors for use in filamentous ascomycetes.
AB  - The green fluorescent protein (GFP) has been established as the premier in vivo
      reporter for investigations of gene expression, protein localization, and cell
      and organism dynamics. The fungal transformation vector pCT74, with sGFP under
      the control of the ToxA promoter from Pyrenophora tritici-repentis, effectively
      expresses GFP in a diverse group of filamentous ascomycetes. Due to the
      versatility of ToxA promoter-driven expression of GFP, we constructed an
      additional set of fluorescent protein expression vectors to expand the color
      palette of fluorescent markers for use in filamentous fungi. EYFP, ECFP and mRFP1
      were successfully expressed from the ToxA promoter in its fungus of origin, P.
      tritici-repentis, and a distant relative, Verticillium dahliae. Additionally the
      ToxB promoter from P. tritici-repentis drove expression of sGFP in V. dahliae,
      suggesting a similar potential to the ToxA promoter for heterologous expression
      in ascomycetes. The suite of fungal transformation vectors presented here promise
      to be useful for a variety of fungal research applications.

PMID- 16596967
TI  - The challenge of characterizing operations in the mechanisms underlying behavior.
AB  - Neuroscience and cognitive science seek to explain behavioral regularities in
      terms of underlying mechanisms. An important element of a mechanistic explanation
      is a characterization of the operations of the parts of the mechanism. The
      challenge in characterizing such operations is illustrated by an example from the
      history of physiological chemistry in which some investigators tried to
      characterize the internal operations in the same terms as the overall
      physiological system while others appealed to elemental chemistry. In order for
      biochemistry to become successful, researchers had to identify a new level of
      operations involving operations over molecular groups. Existing attempts at
      mechanistic explanation of behavior are in a situation comparable to earlier
      approaches to physiological chemistry, drawing their inspiration either from
      overall psychology activities or from low-level neural processes. Successful
      mechanistic explanations of behavior require the discovery of the appropriate
      component operations. Such discovery is a daunting challenge but one on which
      success will be beneficial to both behavioral scientists and cognitive and
      neuroscientists.

PMID- 16596968
TI  - Effects of reinforcement schedule on facilitation of operant extinction by
      chlordiazepoxide.
AB  - Learning and memory are central topics in behavioral neuroscience, and inbred
      mice strains are widely investigated. However, operant conditioning techniques
      are not as extensively used in this field as they should be, given the
      effectiveness of the methodology of the experimental analysis of behavior. In the
      present study, male C57B1/6 mice, widely used as background for transgenic
      studies, were trained to lever press on discrete-trial fixed-ratio 5 or fixed
      interval (11 s or 31 s) schedules of food reinforcement and then exposed to 15
      extinction sessions following vehicle or chlordiazepoxide injections (15 mg/kg
      i.p., administered either prior to all extinction sessions, or prior to the final
      10 extinction sessions). Extinction of operant behavior was facilitated by drug
      administration following training on either schedule, but this facilitation only
      occurred once a number of extinction sessions had taken place. The extinction
      process proceeded more rapidly following fixed-interval training. Resistance to
      extinction was equally high following training with either schedule type, and was
      reduced by drug administration in both cases. These phenomena were evident in
      individual cumulative records and in analyses of group data. Results are
      interpreted in terms of phenomena of operant extinction identified in Skinner's
      (1938) Behavior of Organisms, and by behavioral momentum theory. These procedures
      could be used to extend the contribution of operant conditioning to contemporary
      behavioral neuroscience.

PMID- 16596969
TI  - Differential acquisition of lever pressing in inbred and outbred mice: comparison
      of one-lever and two-lever procedures and correlation with differences in
      locomotor activity.
AB  - Recent progress in mouse genetics has led to an increased interest in developing
      procedures for assessing mouse behavior, but relatively few of the behavioral
      procedures developed involve positively reinforced operant behavior. When operant
      methods are used, nose poking, not lever pressing, is the target response. In the
      current study differential acquisition of milk-reinforced lever pressing was
      observed in five inbred strains (C57BL/6J, DBA/2J, 129X1/SvJ, C3H/HeJ, and
      BALB/cJ) and one outbred stock (CD-1) of mice. Regardless of whether one or two
      levers (an "operative" and "inoperative" lever) were in the operant chamber, a
      concomitant variable-time fixed-ratio schedule of milk reinforcement established
      lever pressing in the majority of mice within two 120-min sessions. Substantial
      differences in lever pressing were observed across mice and between procedures.
      Adding an inoperative lever retarded acquisition in C57BL/6J, DBA/2J, 129X1/SvJ,
      and C3H/HeJ mice, but not in CD-1 and BALB/cJ mice. Locomotor activity was
      positively correlated with number of lever presses in both procedures. Analyses
      of durations of the subcomponents (e.g., time to move from hopper to lever) of
      operant behavior revealed further differences among the six types of mice.
      Together, the data suggest that appetitively reinforced lever pressing can be
      acquired rapidly in mice and that a combination of procedural, behavioral, and
      genetic variables contributes to this acquisition.

PMID- 16596972
TI  - Effects of morphine on temporal discrimination and color matching: general
      disruption of stimulus control or selective effects on timing?
AB  - Discrepant effects of drugs on behavior maintained by temporal-discrimination
      procedures make conclusive statements about the neuropharmacological bases of
      timing difficult. The current experiment examined the possible contribution of a
      general, drug-induced disruption of stimulus control. Four pigeons responded on a
      three-component multiple schedule that included a fixed-interval 2-min, temporal
      discrimination, and color-matching component. Under control conditions, response
      rates and choice responses during the first two components showed evidence of
      control by time, and accuracy for color matching was high in the third component.
      Morphine administration flattened the distribution of fixed-interval responding
      and produced a general disruption of accuracy in the temporal-discrimination
      component, whereas accuracy in the color-matching component was relatively
      unaffected. Analysis of the psychophysical functions from the temporal
      discrimination component indicated that morphine decreased accuracy of temporal
      discrimination by decreasing overall stimulus control, rather than by selectively
      affecting timing. These results suggest the importance of determining the
      neurophysiological bases of stimulus control as it relates to temporal
      discrimination.

PMID- 16596970
TI  - Pilocarpine seizures cause age-dependent impairment in auditory location
      discrimination.
AB  - Children who have status epilepticus have continuous or rapidly repeating
      seizures that may be life-threatening and may cause life-long changes in brain
      and behavior. The extent to which status epilepticus causes deficits in auditory
      discrimination is unknown. A naturalistic auditory location discrimination method
      was used to evaluate this question using an animal model of status epilepticus.
      Male Sprague-Dawley rats were injected with saline on postnatal day (P) 20, or a
      convulsant dose of pilocarpine on P20 or P45. Pilocarpine on either day induced
      status epilepticus; status epilepticus at P45 resulted in CA3 cell loss and
      spontaneous seizures, whereas P20 rats had no cell loss or spontaneous seizures.
      Mature rats were trained with sound-source location and sound-silence
      discriminations. Control (saline P20) rats acquired both discriminations
      immediately. In status epilepticus (P20) rats, acquisition of the sound-source
      location discrimination was moderately impaired. Status epilepticus (P45) rats
      failed to acquire either sound-source location or sound-silence discriminations.
      Status epilepticus in rat causes an age-dependent, long-term impairment in
      auditory discrimination. This impairment may explain one cause of impaired
      auditory location discrimination in humans.

PMID- 16596973
TI  - Derived stimulus relations, semantic priming, and event-related potentials:
      testing a behavioral theory of semantic networks.
AB  - Derived equivalence relations, it has been argued, provide a behavioral model of
      semantic or symbolic meaning in natural language, and thus equivalence relations
      should possess properties that are typically associated with semantic relations.
      The present study sought to test this basic postulate using semantic priming.
      Across three experiments, participants were trained and tested in two 4-member
      equivalence relations using word-like nonsense words. Participants also were
      exposed to a single- or two-word lexical decision task, and both direct
      (Experiment 1) and mediated (Experiments 2 and 3) priming effects for reaction
      times and event-related potentials were observed within but not across
      equivalence relations. The findings support the argument that derived equivalence
      relations provides a useful preliminary model of semantic relations.

PMID- 16596971
TI  - The role of dopamine in reinforcement: changes in reinforcement sensitivity
      induced by D1-type, D2-type, and nonselective dopamine receptor agonists.
AB  - Dose-dependent changes in sensitivity to reinforcement were found when rats were
      treated with low, moderate, and high doses of the partial dopamine D1-type
      receptor agonist SKF38393 and with the nonselective dopamine agonist apomorphine,
      but did not change when rats were treated with similar doses of the selective
      dopamine D2-type receptor agonist quinpirole. Estimates of bias did not differ
      significantly across exposure to SKF38393 or quinpirole, but did change
      significantly at the high dose of apomorphine. Estimates of goodness of fit (r2)
      did not change significantly during quinpirole exposure. Poor goodness of fit was
      obtained for the high doses of SKF38393 and apomorphine. Decrements in absolute
      rates of responding were observed at the high dose of quinpirole and at the
      moderate and high doses of SKF38393 and apomorphine. Changes in r2 and absolute
      responding may be due to increases in stereotyped behavior during SKF38393 and
      apomorphine exposure that, in contrast to quinpirole, were distant from the
      response lever. The present data provide evidence that sensitivity to reward is
      affected more strongly by dopamine D1-like receptors rather than D2-like
      receptors, consistent with evidence from other studies investigating consummatory
      dopamine behavior and the tonic/phasic dopamine hypothesis.

PMID- 16596974
TI  - Relating derived relations as a model of analogical reasoning: reaction times and
      event-related potentials.
AB  - The current study aimed to test a Relational Frame Theory (RFT) model of
      analogical reasoning based on the relating of derived same and derived difference
      relations. Experiment 1 recorded reaction time measures of similar-similar (e.g.,
      "apple is to orange as dog is to cat") versus different-different (e.g., "he is
      to his brother as chalk is to cheese") derived relational responding, in both
      speed-contingent and speed-noncontingent conditions. Experiment 2 examined the
      event-related potentials (ERPs) associated with these two response patterns. Both
      experiments showed similar-similar responding to be significantly faster than
      different-different responding. Experiment 2 revealed significant differences
      between the waveforms of the two response patterns in the left-hemispheric
      prefrontal regions; different-different waveforms were significantly more
      negative than similar-similar waveforms. The behavioral and neurophysiological
      data support the RFT prediction that, all things being equal, similar-similar
      responding is relationally "simpler" than, and functionally distinct from,
      different-different analogical responding. The ERP data were fully consistent
      with findings in the neurocognitive literature on analogy. These findings
      strengthen the validity of the RFT model of analogical reasoning and supplement
      the behavior-analytic approach to analogy based on the relating of derived
      relations.

PMID- 16596975
TI  - On aims and methods in the neuroimaging of derived relations.
AB  - Ingenious and seemingly powerful technologies have been developed recently that
      enable the visualization in some detail of events in the brain concomitant upon
      the ongoing behavioral performance of a human participant. Measurement of such
      brain events offers at the very least a new set of dependent variables in
      relation to which the independent variables familiarly manipulated in the operant
      laboratory may be explored. Two related paradigms in which a start has been made
      in such research concern the derivation of novel or emergent relations from a
      baseline set of trained relations, and include the phenomenon of transitive
      inference (TI), observed in studies of stimulus equivalence (SE) and serial
      learning (SL) or seriation. This paper reviews some published and forthcoming
      neuroimaging studies of these and related phenomena, and considers how this line
      of research both demands and represents a welcome synthesis between types of
      question and levels of explanation in behavioral science that often have been
      seen as antithetical.

PMID- 16596976
TI  - Medial prefrontal cortex lesions abolish contextual control of competing
      responses.
AB  - There is much debate as to the extent and nature of functional specialization
      within the different subregions of the prefrontal cortex. The current study was
      undertaken to investigate the effect of damage to medial prefrontal cortex
      subregions in the rat. Rats were trained on two biconditional discrimination
      tasks, one auditory and one visual, in two different contexts. At test, they
      received presentations of audiovisual compounds of these training stimuli in
      extinction. These compounds had dictated either the same (congruent trials) or
      different (incongruent trials) responses during training. In sham-operated
      controls, contextual cues came to control responding to conflicting information
      provided by incongruent stimulus compounds. Experiment 1 demonstrated that this
      contextual control of responding was not evident in individual rats with large
      amounts of damage that included the prelimbic and cingulate subregions of the
      prefrontal cortex. Experiment 2 further dissociated the result of Experiment 1,
      demonstrating that lesions specific to the anterior cingulate cortex were
      sufficient to produce a deficit early on during presentation of an incongruent
      stimulus compound but that performance was unimpaired as presentation progressed.
      This early deficit suggests a role for the anterior cingulate cortex in the
      detection of response conflict, and for the medial prefrontal cortex in the
      contextual control of competing responses, providing evidence for functional
      specialization within the rat prefrontal cortex.

PMID- 16596977
TI  - Integrating functional neuroimaging and human operant research: brain activation
      correlated with presentation of discriminative stimuli.
AB  - Results of numerous human imaging studies and nonhuman neurophysiological studies
      on "reward" highlight a role for frontal, striatal, and thalamic regions in
      operant learning. By integrating operant and functional neuroimaging
      methodologies, the present investigation examined brain activation to two types
      of discriminative stimuli correlated with different contingencies. Prior to
      neuroimaging, 10 adult human subjects completed operant discrimination training
      in which money was delivered following button pressing (press-money contingency)
      in the presence of one set of discriminative stimuli, and termination of trials
      followed not responding (no response-next trial contingency) in the presence of a
      second set of discriminative stimuli. After operant training, subjects were
      instructed to memorize a third set of control stimuli unassociated with
      contingencies. Several hours after training, functional magnetic resonance
      imaging was performed while subjects viewed discriminative and control stimuli
      that were presented individually for 1,500 ms per trial, with stimulus
      presentations occurring, on average, every 6 s. Activation was found in frontal
      and striatal brain regions to both sets of discriminative stimuli relative to
      control stimuli. In addition, exploratory analyses highlighted activation
      differences between discriminative stimuli. The results demonstrate the utility
      of coupling operant and imaging technologies for investigating the neural
      substrates of operant learning in humans.

PMID- 16596978
TI  - Neural correlates of a default response in a delayed go/no-go task.
AB  - Working memory, the ability to temporarily retain task-relevant information
      across a delay, is frequently investigated using delayed matching-to-sample
      (DMTS) or delayed Go/No-Go tasks (DGNG). In DMTS tasks, sample cues instruct the
      animal which type of response has to be executed at the end of a delay.
      Typically, performance decreases with increasing delay duration, indicating that
      working memory fades across a delay. However, no such performance decrease has
      been found when the sample cues exist of present vs. absent stimuli, suggesting
      that pigeons do not rely on working memory, but seem to respond by default in
      those trials. We trained 3 pigeons in a DGNG task and found a similar default
      response pattern: The diverging slopes of the retention functions on correct Go
      and No-Go trials suggested that pigeons by default omitted their response
      following No-Go stimuli, but actively retained task-relevant information across
      the delay for successful responses on Go trials. We conducted single-cell
      recordings in the avian nidopallium caudolaterale, a structure comparable to the
      mammalian prefrontal cortex. On Go trials, many neurons displayed sustained
      elevated activity during the delay preceding the response, replicating previous
      findings and suggesting that task-relevant information was neurally represented
      and maintained across the delay. However, the same units did not show enhanced
      delay activity preceding correct response suppressions in No-Go trials. This
      activation-inactivation pattern presumably constitutes a neural correlate of the
      default response strategy observed in the DGNG task.

PMID- 16596979
TI  - Prefrontal brain activity predicts temporally extended decision-making behavior.
AB  - Although functional neuroimaging studies of human decision-making processes are
      increasingly common, most of the research in this area has relied on passive
      tasks that generate little individual variability. Relatively little attention
      has been paid to the ability of brain activity to predict overt behavior. Using
      functional magnetic resonance imaging (fMRI), we investigated the neural
      mechanisms underlying behavior during a dynamic decision task that required
      subjects to select smaller, short-term monetary payoffs in order to receive
      larger, long-term gains. The number of trials over which the longterm gains
      accrued was manipulated experimentally (2 versus 12). Event-related neural
      activity in right lateral prefrontal cortex, a region associated with high-level
      cognitive processing, selectively predicted choice behavior in both conditions,
      whereas insular cortex responded to fluctuations in amount of reward but did not
      predict choice behavior. These results demonstrate the utility of a functional
      neuroimaging approach in behavioral psychology, showing that (a) highly
      circumscribed brain regions are capable of predicting complex choice behavior,
      and (b) fMRI has the ability to dissociate the contributions of different neural
      mechanisms to particular behavioral tasks.

PMID- 16596980
TI  - Dynamic response-by-response models of matching behavior in rhesus monkeys.
AB  - We studied the choice behavior of 2 monkeys in a discrete-trial task with
      reinforcement contingencies similar to those Herrnstein (1961) used when he
      described the matching law. In each session, the monkeys experienced blocks of
      discrete trials at different relative-reinforcer frequencies or magnitudes with
      unsignalled transitions between the blocks. Steady-state data following
      adjustment to each transition were well characterized by the generalized matching
      law; response ratios undermatched reinforcer frequency ratios but matched
      reinforcer magnitude ratios. We modelled response-by-response behavior with
      linear models that used past reinforcers as well as past choices to predict the
      monkeys' choices on each trial. We found that more recently obtained reinforcers
      more strongly influenced choice behavior. Perhaps surprisingly, we also found
      that the monkeys' actions were influenced by the pattern of their own past
      choices. It was necessary to incorporate both past reinforcers and past choices
      in order to accurately capture steady-state behavior as well as the fluctuations
      during block transitions and the response-by-response patterns of behavior. Our
      results suggest that simple reinforcement learning models must account for the
      effects of past choices to accurately characterize behavior in this task, and
      that models with these properties provide a conceptual tool for studying how both
      past reinforcers and past choices are integrated by the neural systems that
      generate behavior.

PMID- 16596981
TI  - Linear-Nonlinear-Poisson models of primate choice dynamics.
AB  - The equilibrium phenomenon of matching behavior traditionally has been studied in
      stationary environments. Here we attempt to uncover the local mechanism of choice
      that gives rise to matching by studying behavior in a highly dynamic foraging
      environment. In our experiments, 2 rhesus monkeys (Macacca mulatta) foraged for
      juice rewards by making eye movements to one of two colored icons presented on a
      computer monitor, each rewarded on dynamic variable-interval schedules. Using a
      generalization of Wiener kernel analysis, we recover a compact mechanistic
      description of the impact of past reward on future choice in the form of a Linear
      Nonlinear-Poisson model. We validate this model through rigorous predictive and
      generative testing. Compared to our earlier work with this same data set, this
      model proves to be a better description of choice behavior and is more tightly
      correlated with putative neural value signals. Refinements over previous models
      include hyperbolic (as opposed to exponential) temporal discounting of past
      rewards, and differential (as opposed to fractional) comparisons of option value.
      Through numerical simulation we find that within this class of strategies, the
      model parameters employed by animals are very close to those that maximize reward
      harvesting efficiency.

PMID- 16596982
TI  - Bridging the gap between brain and behavior: cognitive and neural mechanisms of
      episodic memory.
AB  - The notion that non-human animals are capable of episodic memory is highly
      controversial. Here, we review recent behavioral work from our laboratory showing
      that the fundamental features of episodic memory can be observed in rats and
      that, as in humans, this capacity relies on the hippocampus. We also discuss
      electrophysiological evidence, from our laboratory and that of others, pointing
      to associative and sequential coding in hippocampal cells as potential neural
      mechanisms underlying episodic memory.

PMID- 16596983
TI  - Neuroscience and learning: lessons from studying the involvement of a region of
      cerebellar cortex in eyeblink classical conditioning.
AB  - How the nervous system encodes learning and memory processes has interested
      researchers for 100 years. Over this span of time, a number of basic neuroscience
      methods has been developed to explore the relationship between learning and the
      brain, including brain lesion, stimulation, pharmacology, anatomy, imaging, and
      recording techniques. In this paper, we summarize how different research
      approaches can be employed to generate converging data that speak to how
      structures and systems in the brain are involved in simple associative learning.
      To accomplish this, we review data regarding the involvement of a particular
      region of cerebellar cortex (Larsell's lobule HVI) in the widely used paradigm of
      classical eyeblink conditioning. We also present new data on the role of lobule
      HVI in eyeblink conditioning generated by combining temporary brain inactivation
      and single-cell recording methods, an approach that looks promising for further
      advancing our understanding of relationships between brain and behavior.

PMID- 16596986
TI  - Naming our concerns about neuroscience: a review of Bennett and Hacker's
      philosophical foundations of neuroscience.
AB  - Bennett and Hacker use conceptual analysis to appraise the theoretical language
      of modern cognitive neuroscientists, and conclude that neuroscientific theory is
      largely dualistic despite the fact that neuroscientists equate mind with the
      operations of the brain. The central error of cognitive neuroscientists is to
      commit the mereological fallacy, the tendency to ascribe to the brain
      psychological concepts that only make sense when ascribed to whole animals. The
      authors review how the mereological fallacy is committed in theories of memory,
      perception, thinking, imagery, belief, consciousness, and other psychological
      processes studied by neuroscientists, and the consequences that fallacious
      reasoning have for our understanding of how the brain participates in cognition
      and behavior. Several behavior-analytic concepts may themselves be nonsense based
      on thorough conceptual analyses in which the criteria for sense and nonsense are
      found in the ways the concepts are used in ordinary language. Nevertheless, the
      authors' nondualistic approach and their consistent focus on behavioral criteria
      for the application of psychological concepts make Philosophical Foundations of
      Neuroscience an important contribution to cognitive neuroscience.

PMID- 16596985
TI  - Behavioral perspectives on the neuroscience of drug addiction.
AB  - Neuroscientific approaches to drug addiction traditionally have been based on the
      premise that addiction is a process that results from brain changes that in turn
      result from chronic administration of drugs of abuse. An alternative approach
      views drug addiction as a behavioral disorder in which drugs function as
      preeminent reinforcers. Although there is a fundamental discrepancy between these
      two approaches, the emerging neuroscience of reinforcement and choice behavior
      eventually may shed light on the brain mechanisms involved in excessive drug use.
      Behavioral scientists could assist in this understanding by devoting more
      attention to the assessment of differences in the reinforcing strength of drugs
      and by attempting to develop and validate behavioral models of addiction.

PMID- 16596984
TI  - Neuronal substrates of relapse to cocaine-seeking behavior: role of prefrontal
      cortex.
AB  - The return to drug seeking, even after prolonged periods of abstinence, is a
      defining feature of cocaine addiction. The neural circuitry underlying relapse
      has been identified in neuropharmacological studies of experimental animals,
      typically rats, and supported in brain imaging studies of human addicts. Although
      the nucleus accumbens (NAcc), which has long been implicated in goal-directed
      behavior, plays a critical role in this circuit, the prefrontal cortex (PFC)
      appears to process the events that directly trigger relapse: exposure to acute
      stress, cues previously associated with the drug, and the drug itself. In this
      paper, we review animal models of relapse and what they have revealed about the
      mechanisms underlying the involvement of the NAcc and PFC in cocaine-seeking
      behavior. We also present electrophysiological data from PFC illustrating how the
      hedonic, motor, motivational, and reinforcing effects of cocaine can be analyzed
      at the neuronal level. Our preliminary findings suggest a role for PFC in
      processing information related to cocaine seeking but not the hedonic effects of
      the drug. Further use of this recording technology can help dissect the functions
      of PFC and other components of the neural circuitry underlying relapse.

PMID- 16596987
TI  - Synthesis of 6-hydroxy-7-methoxy-4-oxo-4H-chromene-2-carboxylic acid N-alkyl
      amides and their antioxidant activity.
AB  - A series of 6-hydroxy-7-methoxy-4-oxo-4H-chromene-2-carboxylic acid N-alkyl
      amides (3a-g) were synthesized and their antioxidant activities were evaluated
      using rat brain homogenates.

PMID- 16596988
TI  - Gadolinium-chlorin is potentially a new tumor specific MRI contrast agent.
AB  - In this study, a newly-synthesized metalloporphyrin, Gd-chlorin (PB Chlorin), was
      investigated by using a simple tissue phantom to test its efficacy as an MRI
      contrast agent. This study demonstrated the potential activity of Gd-chlorin as
      not only a MRI contrast agent, but also as a PDT photosensitizer by using a
      simple tissue phantom and conducting a very brief MRI experiment.

PMID- 16596989
TI  - Acyl-CoA: cholesterol acyltransferase inhibitors from Ilex macropoda.
AB  - Twigs from Ilex macropoda were extracted with MeOH, and the concentrated extracts
      were partitioned with CH2Cl2, EtOAc, n-BuOH, and H2O. Repeated column
      chromatography of the CH2Cl2 fraction ultimately resulted in the isolation of two
      compounds, via activity-guided fractionation, using ACAT inhibitory activity
      measurements. According to the physico-chemical data, the chemical structures of
      these isolated compounds were identified as lupeol (1) and betulin (2). Compounds
      1 and 2 were shown to inhibit the activity of hACAT-1 and hACAT-2 in a dose
      dependent manner, and compounds 1 and 2 inhibited hACAT-1 with IC50 values of 48
      and 83 microM, respectively.

PMID- 16596990
TI  - New butyrylcholinesterase inhibitory triterpenes from Salvia santolinifolia.
AB  - Slavins A (1) and B (2), the new amyrin type triterpenes, have been isolated from
      the chloroform soluble fraction of Salvia santolinifolia and assigned structures
      on the basis of spectral studies including 2D NMR. Both the compounds displayed
      inhibitory potential against the enzyme butyrylcholinesterase.

PMID- 16596991
TI  - Flavones with free radical scavenging activity from Goniothalamus tenuifolius.
AB  - From the leaves of Goniothalamus tenuifolius, a new natural product namely 3'
      hydroxy-3,5,7,4'-tetramethoxyflavone (1) was isolated, along with seven other
      known compounds (2-8). Each of these isolates was evaluated for free radical
      scavenging activity on the DPPH decoloration test. The data obtained in this
      study suggested that the ortho 3',4'-diphenolic structure was essential for the
      activity of these flavonol derivatives.

PMID- 16596992
TI  - Cytotoxic terpenes and lignans from the roots of Ainsliaea acerifolia.
AB  - The chromatographic separation of the MeOH extract of the roots of Ainsliaea
      acerifolia (Compositae) led to the isolation of six known terpenes and two known
      lignans. Their structures were identified by spectroscopic methods as mokko
      lactone (1), betulonic acid (2), betulinic acid (3), zaluzanin C (4), 1beta
      hydroperoxygermacra-4(15),5,10(14)-triene (5), pluviatilol (6), (+)
      syringaresinol (7), and glucozaluzanin C (8). Compounds 1 approximately 4 and 8
      showed non-specific significant cytotoxicity against five human tumor cell lines
      with ED50 values ranging from 0.36 approximately 5.54 microg/mL.

PMID- 16596993
TI  - Chemopreventive effect of protein extract of Asterina pectinifera in HT-29 human
      colon adenocarcinoma cells.
AB  - We investigated the effect of protein extract of Asterina pectinifera on the
      activity of 4 enzymes that may play a role in adenocarcinoma of the colon:
      quinone reductase (QR), glutathione S-transferase (GST), ornithine decarboxylase
      (ODC), and cyclooxygenase (COX)-2. QR and GST activity increased in HT-29 human
      colon adenocarcinoma cells increased that had been exposed to 4 concentrations of
      the protein extract (80, 160, 200, and 240 microg/mL). Additionally, 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced ODC activity decreased
      significantly in cells exposed to the extract in concentrations of 160 microg/mL
      (p<0.05), 200 microg/mL (p<0.005), and 240 microg/mL (p<0.005). TPA-induced COX-2
      activity also decreased in cells exposed to extract concentrations of 10, 20, 40,
      and 60 microg/mL. COX-2 expression was also inhibited in cells exposed to this
      extract. These results suggest that this protein extract of A pectinifera has
      chemopreventive activity in HT-29 human colon adenocarcinoma cells, and
      therefore, may have the potential to function as a chemopreventive agent in human
      colorectal cancer.

PMID- 16596994
TI  - Protection of peroxynitrite-induced DNA damage by dietary antioxidants.
AB  - The present study was undertaken to test the hypothesis that dietary antioxidants
      protect DNA damage induced by peroxynitrite, a potent physiological inorganic
      toxin. The present study showed that dietary antioxidants such as (-)
      epigallocatechin gallate, quercerin, rutin, resveratrol, and ursolic acid inhibit
      single strand breaks in supercoiled plasmid DNA induced by 3-morpholinosydnomine
      N-ethylcarbamide (SIN-1), a generator of peroxynitrite through the reaction
      between nitric oxide and superoxide anion. The formation of 8-hydroxy-2'
      deoxyguanosine (8-OH-dG) in calf thymus DNA by SIN-1 was also inhibited by
      dietary antioxidants. When U937 cells were incubated with 1 mM SIN-1 bolus, a
      significant increase of 8-OH-dG level was observed. However, oxidative DNA damage
      was significantly lower in the cells pre-treated with dietary antioxidants when
      cells were exposed to SIN-1.

PMID- 16596995
TI  - Stimulation of cell growth by erythropoietin in RAW264.7 cells: association with
      AP-1 activation.
AB  - Erythropoietin (EPO), a hematopoietic factor, is required for normal erythrocyte
      developments, but it has been demonstrated to have many other functions, and its
      receptor is localized in other tissues. In the present study, we investigated
      whether EPO can promote other cell proliferation and possible molecular
      mechanisms. EPO restored the inhibition of the RAW264.7 and PC12 cell growth by
      fetal bovine serum (FBS) withdrawal in a dose dependent manner, but not that of
      other cell types tested. The restoring effect of EPO was completed when the
      RAW264.7 cells were cultured in the medium containing as low as 3% of FBS, and 10
      U/mL EPO could replace FBS. The restoring effect of EPO in the RAW264.7 cells was
      associated with the increased of c-Fos and c-Jun expression as well as AP-1
      activation. These data demonstrate that EPO can stimulate RAW264. 7 cell as well
      as PC12 cell growth even when the cells were cultured without FBS or in the
      presence of small amounts of FBS in the medium, and this stimulating effect is
      associated with the activation of AP-1 transcription factor.

PMID- 16596996
TI  - Proteomic analysis and the antimetastatic effect of N-(4-methyl)phenyl-O-(4
      methoxy) phenyl-thionocarbamate-induced apoptosis in human melanoma SK-MEL-28
      cells.
AB  - We employed human SK-MEL-28 cells as a model system to identify cellular proteins
      that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)
      induced apoptosis based on a proteomic approach. Cell viability tests revealed
      that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT
      cells in a dose-dependent manner after treatment with MMTC. Two-dimensional
      electrophoresis in conjunction with matrix-assisted laser desorption/ionization
      time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a
      protein database further revealed that the MMTC-induced apoptosis is accompanied
      by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kappaB
      inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S
      specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras
      related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase,
      tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear
      receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested.
      MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that
      MMTC had little angiogenic effect because it did not suppress the proliferation
      of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic
      and metastatic agents against the SK-MEL-28 human melanoma cell line.

PMID- 16596997
TI  - Suppressive effects of young radish cultivated with sulfur on growth and
      metastasis of B16-F10 melanoma cells.
AB  - The oral administration of extracts of young radishes cultivated with sulfur
      after intravenous tumor cell injection achieved a marked reduction of pulmonary
      colonization in mice. Treatment of the mice with extracts of young radish
      cultivated with sulfur did not show any increase in the number of CD8+ or NK T
      cells in the spleen, indicating no influence on host immunity. Sulforaphane,
      which could be a candidate for an active compound from young radishes cultivated
      with sulfur, inhibited cell growth of B16-F10 melanoma cells. In addition,
      extracts of the young radish cultivated with sulfur-fed group showed enhanced
      quinine reductase (QR) activities in the liver and lung and a slight increase of
      glutathione S-transferase (GST) activity in the liver. These results suggested
      that the administration of extracts of young radishes cultivated with sulfur
      suppressed pulmonary tumorigenesis, possibly due to increased activity of
      detoxification enzymes in the liver and lung, and partly due to cell
      cytotoxicity.

PMID- 16596998
TI  - Degradation of bradykinin, a cardioprotective substance, during a single passage
      through isolated rat-heart.
AB  - Angiotensin converting enzyme (ACE) inhibitors have cardioprotective effects in
      different species including human. This cardioprotective effect is mainly due to
      the inhibition of bradykinin (BK) degradation rather than inhibition of the
      conversion of angiotensin I to angiotensin II. Bradykinin, a nonapeptide, has
      been considered to be the potential target for various enzymes including ACE,
      neutral endopeptidase 24.11, carboxypeptidase M, carboxypeptidase N, proline
      aminopeptidase, endopeptidase 24.15, and meprin. In the present study, the
      coronary vascular beds of Sprague Dawley rat isolated hearts were perfused
      (single passage) with Krebs solution alone or with different concentrations of BK
      i.e. 2.75x10(-10), 10(-7), 10(-6) and 10(-5) M solution. Percent degradation of
      BK was determined by radioimmunoassay. The degradation products of BK after
      passing through the isolated rat-hearts were determined using RP-HPLC and mass
      spectroscopy. All the four doses of BK significantly decreased the perfusion
      pressure during their passage through the hearts. The percentage degradation of
      all four doses was decreased as the concentration of drug was increased, implying
      saturation of a fixed number of active sites involved in BK degradation.
      Bradykinin during a single passage through the hearts degraded to give [1-7]-BK
      as the major metabolite, and [1-8]-BK as a minor metabolite, detected on HPLC.
      Mass spectroscopy not only confirmed the presence of these two metabolites but
      also detected traces of [1-5]-BK and arginine. These findings showed that
      primarily ACE is the major cardiac enzyme involved in the degradation of
      bradykinin during a single passage through the coronary vascular of bed the
      healthy rat heart, while carboxypeptidase M may have a minor role.

PMID- 16596999
TI  - Candida albicans can utilize siderophore during candidastasis caused by
      apotransferrin.
AB  - Ability of iron acquisition of pathogenic microorganisms functions as a virulence
      factor. Candida albicans, a fungal pathogen that requires iron for growth, is
      susceptible to growth retardation by high-affinity iron binding proteins such as
      transferrin. Recently, we reported that C. albicans could utilize the heme as a
      part of heme-containing proteins dissociated by heme oxygenase, CaHMX1. In search
      of another pathway that C. albicans can use to bypass the growth regulation
      produced by iron limitation, this present study examined utilization of non
      candidal siderophores such as Desferal and rhodotorulic acid (RA) for acquisition
      of inorganic iron by the fungus. C. albicans secreting no siderophores was
      cultured in iron-free (pretreated with apotransferrin for 24 h) (culture medium).
      Once growth of the yeast reached stasis from iron starvation, a siderophore was
      added to the culture media. Results showed that cultures containing
      apotransferrin within a dialysis membrane recovered growth to the level of
      untreated controls, whereas C. albicans yeast cells in direct contact with
      soluble iron-free (apo) transferrin recovered growth only partially. When static
      growth from iron limitation was reached, the addition of siderophore
      apotransferrin complex to culture medium also permitted the yeast to recover
      growth from apotransferrin growth regulation. All the data show that C. albicans
      can utilize the non-candidal siderophores for iron acquisition under transferrin
      regulation as can pathogenic bacteria.

PMID- 16597000
TI  - Salicornia herbacea prevents high fat diet-induced hyperglycemia and
      hyperlipidemia in ICR mice.
AB  - Salicornia herbacea L. (Chenopodiaceae) has been used as a seasoned vegetable by
      living in coastal areas. S. herbacea (SH) has been demonstrated to stimulate
      cytokine production, nitric oxide release, and to show anti-oxidative effect. In
      a series of investigations to develop potential anti-diabetic and/or anti
      hyperlipidemic agents from Korean indigenous plants, 50% ethanol extract of
      Salicornia herbacea was found to prevent the onset of the hyperglycemia and
      hyperlipidemia induced by high fat diet in ICR mice. At 6 week old, the ICR mice
      were randomly divided into five groups; two control and three treatment groups.
      The control mice were to receive either a regular diet (RD) or high-fat diet
      (HFD), and the treatment groups were fed a high fat diet with either 350 mg/kg,
      700 mg/kg of SH (SH350 and SH700) or 250 mg/kg of metformin (MT250) for a 10-week
      period. SH not only reduced body weight but also corrected associated
      hyperglycemia and hyperlipidemia in a dose dependent manner. SH exerted
      beneficial effects on the plasma glucose and lipid homeostasis possibly ascribed
      to its specific effects on lipogenesis related genes (SREBP1a, FAS, GAPT), and
      PEPCK, glucose 6-phosphatase gene expressions in liver. Ethanol extract of S.
      herbacea has potential as a preventive agent for type 2 diabetes (and possibly
      hyperlipidemia) and deserves future clinical trial.

PMID- 16597002
TI  - Disease management.

PMID- 16597001
TI  - Disaster preparedness.

PMID- 16597003
TI  - Electronic medical records.

PMID- 16597004
TI  - E-prescribing.

PMID- 16597005
TI  - National standards.

PMID- 16597006
TI  - Pay for performance.

PMID- 16597007
TI  - Personal health records.

PMID- 16597008
TI  - RHIOs.

PMID- 16597009
TI  - Wireless security.

PMID- 16597010
TI  - Calculated risks pay off. Mitchell Adams' financial vision steers Massachusetts
      toward 100 percent CPOE.

PMID- 16597011
TI  - Organizing quality improvement. Antonio Linares and his team deliver on their
      assignment to develop a catalyst for electronic record adoption.

PMID- 16597012
TI  - Room service. Function is fueling new forms in the medical cart sector.

PMID- 16597013
TI  - Nurses: critical members of the IT team.

PMID- 16597014
TI  - Technology at the crossroads in managed care. Change is good, but sometimes ever
      improving database technology impedes business processes.

PMID- 16597015
TI  - Predicting the tune at HIMSS. Two industry leaders are expecting business as
      usual at the upcoming healthcare technology show.

PMID- 16597016
TI  - Garbage in, garbage out. Don't expect technology solutions to fix broken workflow
      processes.

PMID- 16597017
TI  - Mobile charge capture. One group practice uses IT to improve coding and billing
      processes.

PMID- 16597018
TI  - Connecting clinics via the Web. Document imaging can solve medical record access
      issues.

PMID- 16597019
TI  - "C"ing is believing. The three C's of healthcare might just be communication,
      collaboration and commerce.

PMID- 16597020
TI  - Crisis communications. Take action now to help stay connected during an
      emergency.

PMID- 16597021
TI  - Loading for bear. Incorporation of clinical data is integral to EHR success.

PMID- 16597022
TI  - Consolidation alters the mix. Several healthcare informatics 100 companies see
      vigorous M&A activity.

PMID- 16597023
TI  - The real story on EHR tales.

PMID- 16597024
TI  - Do you recall testing your AED lately? These devices can save lives, but only if
      they're properly maintained.

PMID- 16597025
TI  - Cutting costs with disease management. CMS contractors guarantee 5 percent
      savings.

PMID- 16597026
TI  - Active RFID popular pick. ROI for the passive form is weak, but overall prospects
      look better, says study.

PMID- 16597027
TI  - The second time around. Implementing successful technology sometimes means
      starting over.

PMID- 16597028
TI  - IT gets skeletal. The Medical Innovation Summit urges the orthopedic community
      into fast forward.

PMID- 16597029
TI  - [Functional expression of adenylyl cyclase and phosphodiesterase in ejaculated
      human spermatozoa].
AB  - OBJECTIVE: To compare the differences of expressions of adenylyl cyclase (AC) and
      phosphodiesterase (PDE) in ejaculated spermatozoa between healthy volunteers and
      the patients with asthenospermia. METHODS: Ejaculated spermatozoa were collected
      from healthy volunteers and the patients with asthenospermia. Reverse
      transcription polymerase chain reaction (RT-PCR) was used to detect mRNA
      expression of AC and PDE subtypes in human spermatozoa. The concentrations of
      cAMP and cGMP in the samples were detected by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Compared with healthy volunteers, expression of sAC mRNA and
      concentration of cAMP were significantly decreased in the patients with
      asthenospermia (P < 0.01) , while the expression of PDE4C mRNA was significantly
      increased at the same time (P <0.01). There were no marked differences in the
      expression of ACIII mRNA and concentration of cGMP between the two groups.
      CONCLUSION: The sAC down-regulation and PDE4C up-regulation are possible reasons
      for asthenospermia.

PMID- 16597030
TI  - [Screening for Y chromosomal microdeletions in AZF region with modified multiplex
      PCR].
AB  - OBJECTIVE: Screening for Y chromosomal microdeletions in azoospermia factor (AZF)
      region with modified multiplex PCR. METHODS: 160 cases with spermatogenetic
      failure were recruited in the experimental group, while 90 cases of donors in
      controls. According to the laboratory guidelines supported by European Academy of
      Andrology (EAA) and European Molecular Genetics Quality Network (EMQN), Y
      chromosomal microdeletions in AZFa, b, c regions were screened with multiplex
      PCR. The primers of sequence targeted sites (STSs) and conditions of PCR were
      modified. RESULTS: Using modified multiplex PCR, 14 (8.75%) cases with Y
      chromosomal microdeletions were found in the experimental group, while no case in
      controls. There were 12 cases in AZFc, 1 case in AZFa + b + c, 1 case in AZFb +
      c. According to statistics, the difference between two groups was significant (P
      <0.001). Reaction products could be clearly separated with agarose gel and
      finished in 1 h. CONCLUSION: Modified multiplex PCR protocols supported by EAA
      and EMQN proved to be very accurate, sensitive and quick, which could be put into
      screening practice for Y chromosomal microdeletions in AZF region.

PMID- 16597031
TI  - [Relationship between germ cell apoptosis and Sertoli cell vimentin in
      prepubertal rats induced by local exposure to heat].
AB  - OBJECTIVE: To explore the relationship between germ cell apoptosis and the
      expression as well as the distribution of Sertoli cell vimentin induced by local
      exposure to heat. METHODS: Local short-term exposure of prepubertal male rats
      testis to heat (43 degrees C for 15 min). Histochemical method was used to
      observe morphological characteristics of seminiferous tubule. The distribution
      and expression of Sertoli cell cytoskeletons were analyzed by
      immunohistochemistry and germ cell apoptosis was evaluated by TUNEL technique at
      different hour-intervals. RESULTS: After 2 h and 4 h heat exposure, the
      disattachment phenomenon between Sertoli cell and spermatogonia occurred.
      Spermatogonia arranged in disorder and displaced away from the basement membrane
      of seminiferous tubules. Immunohistochemical staining showed that vimentin
      positive staining was seen radiating from the Sertoli cell perinuclear region
      with apical "spoke-like" pattern in controls. There was an intense vimentin
      immunoreactivity surrounding Sertoli cell nuclei along with the collapse of the
      apical extensions in 2 h group, but no significant difference compared with the
      controls. The expressions of vimentin in 12 h and 24 h groups were higher than
      those of the controls (P <0.01), respectively. TUNEL showed that incidence of
      apoptosis was observed to increases markedly in 12 h and 24 h groups, but it was
      found that the incidences of apoptotic events were decreased in these two groups
      compared with the controls. CONCLUSION: The changes of expression and
      distribution of Sertoli cell vimentin filaments correlate with the increased germ
      cell apoptosis. Local heat may disrupt spermatogenesis by injuring Sertoli cell
      directly.

PMID- 16597032
TI  - [Expression of cyclooxygenase-2 and vascular endothelial growth factor in human
      prostate cancer and its significance].
AB  - OBJECTIVE: To evaluate expressions of cyclooxygenase-2 (COX-2) and vascular
      endothelial growth factor (VEGF) in primary prostate cancer and its clinical
      significance. METHODS: Expressions of COX-2 and VEGF were detected by
      immunohistochemical assay in tissues of 40 prostate cancer and 10 benign
      prostatic hyperplasia samples. RESULTS: COX-2 and VEGF levels in prostate cancer
      were much higher than those in BPH. The degrees of cancer malignancy and invasion
      positively correlated with the expressions of COX-2 and VEGF. COX-2 level
      positively correlated with VEGF level. CONCLUSION: The abnormal expression of COX
      2 plays an important role in the development of primary prostate cancer. COX-2
      and VEGF are good molecular markers of prostate cancer which are hopeful to be
      used for the assistant diagnosis and the prediction of prognosis of prostate
      cancer.

PMID- 16597033
TI  - [Effect of dihydrotestosterone on the transcriptions and expressions of Smad3 and
      Smad4 in LNCaP cell line].
AB  - OBJECTIVE: To investigate the effect of dihydrotestosterone (DHT) on the gene
      transcriptions and expressions of Smad3 and Smad4 in androgen dependent prostate
      cancer cell line LNCaP, and whether this effect can be suppressed by the androgen
      receptor inhibitor flutamide. METHODS: The androgen dependent prostate cancer
      cell line LNCaP was cultured in RPMI 1640 medium and treated with different
      concentrations of DHT(2, 10, 50 nmol/L) and flutamide (100 nmol/L). Quantitative
      reverse transcription PCR (RT-PCR) was used to detect the mRNAs of Smad3 and
      Smad4. The expressions of Smad3 and Smad4 protein were detected by Western blot
      assay. RESULTS: Compared with the control group without any DHT or flutamide,
      higher concentration(10, 50 nmol/L) of DHT enhanced the transcription of Smad3
      mRNA (P <0.05). Serial concentrations of DHT increased the expression of Smad3
      protein(P < 0.05). Flutamide inhibited the up-regulation of both Smad3 mRNA
      transcription and expression significantly (P <0.05). 10 nmol/L DHT significantly
      suppressed the transcription of Smad4 (P <0.05). There was considerable
      suppressions of Smad4 expression at the presence of DHT in different
      concentrations (P < 0.05). And the degree of this suppression was more
      significant than that of DHT on Smad4 mRNA transcription. Flutamide inhibited the
      suppressive effects of DHT on both Smad4 mRNA transcription and expression.
      CONCLUSION: DHT can enhance the transcription and expression of Smad3, while it
      decreases the transcription and expression of Smad4 in LNCaP cell line. There is
      a possible crosstalk between the AR signal and TGF-beta signal passways at the
      level of Smads.

PMID- 16597035
TI  - [Papillary cystadenocarcinoma in a Mullerian duct cyst: report of a case with
      literature review].
AB  - OBJECTIVE: To study the diagnosis and treatment of Mullerian duct cysts and their
      involvement with malignancy. METHODS: A 44-year-old male patient with papillary
      cystadenocarcinoma involving a Mullerian duct cyst was presented. The
      presentation treatment, and pathological and radiological appearances were
      retrospectively analysed and discussed with literature review. The main
      manifestation was intermittent episode of hemospermia accompanying terminal
      hematuria and infertility for 15 years. Final diagnosis was determined by the
      findings of transrectal ultrasound scan, CT scan, MRI imaging, cystoscopic
      examination and biopsy. RESULTS: Exploratory laparotomy was performed through a
      suprapubic retrovesical approach. The finding that a duct-like wedge of tumor
      tissue passed through the prostate near cyst neck to the posterior urethra
      without affecting the adjacent prostatic tissue during tylectomy confirmed that
      it arises from Mullerian duct system. Pathohistologic examination disclosed a
      papillary cystadenocarcinoma and it infiltrated the wall of the cyst. Both
      seminal vesicles and ejaculatory duct had no carcinoma invasion. CONCLUSION:
      Mullerian duct cyst involving with malignancy is exceedingly rare, the diagnosis
      is based on the findings of transrectal ultrasound scan, CT scan, MRI imaging,
      cystoscopic examination. The final diagnosis depends on the pathohistologic
      examination. Lumpectomy is effective and have a good outcome.

PMID- 16597034
TI  - [Effects of cigarette, alcohol consumption and sauna on sperm morphology].
AB  - OBJECTIVE: To investigate effects of cigarette, alcohol consumption and sauna on
      sperm morphology. METHODS: 602 cases of male infertility were selected from our
      case database, who were divided into three subgroups: smoking (243) ,
      drinking(224), sauna(135) and those without any of the above habits were taken as
      the corresponding controls. The sperm morphology were analyzed by automated sperm
      morphology analyzer(ASMA). A questionnaire was voluntarily filled out by patients
      in order to investigate cigarette, alcohol consumption and sauna frequency.
      RESULTS: The normal morphologic sperm rates in cigarette, alcohol consumption and
      sauna groups were lower than those in the corresponding control groups,
      respectively(P <0.05, P <0.001). Percentages of irregularity head sperm were
      higher than those in normal controls, respectively(P <0.05). CONCLUSION:
      Cigarette, alcohol consumption and sauna could affect sperm morphology,
      especially caused increasing of irregularity head sperm.

PMID- 16597036
TI  - [Comparison of four methods for sperm counting].
AB  - OBJECTIVE: To evaluate the accuracy and precision of 4 methods including
      Hemacytometer, Makler chamber, Cell-VU chamber, and computer-aided semen analysis
      for determining sperm concentration. METHODS: Latex bead solutions with
      concentrations known as (35 +/- 5) x 10(6)/ml and (18.0 +/- 2.5) x 10(6)/ml and
      semen samples (n = 54) were counted by the above 4 methods and the results were
      then compared. RESULTS: Mean bead concentrations for Hemacytometer, Makler, Cell
      VU chambers and CASA were (44.84 +/- 4.86), (52.36 +/- 7.78), (39.70 +/- 4.76),
      (28.53 +/- 2.06) x 10(6)/ml respectively for the standard solution containing (35
      +/- 5) x 10(6)/ml, and (21.04 +/- 1.87), (24.54 +/- 3.67), (19.09 +/- 2.02),
      (14.62 +/- 0.95) x 10(6)/ml respectively for a standard solution containing (18
      +/- 2.5) x 10(6)/ml. The results of Cell-VU chamber were consistently similar and
      close to the standard solutions, while those of Hemacytometer, Makler chambers
      were overestimated, and those of CASA were underestimated. The coefficients of
      variation for Hemacytometer, Makler, Cell-VU chambers and CASA were 10.81%,
      14.86%, 12.80%, and 7.22% respectively for a higher standard solution, while
      8.89%, 14.96%, 10.58%, and 6.50% respectively for a lower standard solution. CASA
      has the lowest CV%. When semen samples were counted, the results of
      Hemacytometer, Makler, Cell-VU chambers and CASA were (76.98 +/- 59.90), (63.89
      +/- 53.84), (45.28 +/- 34.52), (41.96 +/- 31.93) x 10(6)/ml respectively. There
      wasn't any significant difference either between Cell-VU chamber and CASA (P =
      0.71), or between Hemacytometer and Makler chamber (P = 0.14), while there was
      significant difference between Cell-VU chamber or CASA and Hemacytometer or
      Makler chamber (P < 0.05 or P <0.01). CONCLUSION: When counting semen sample,
      there wasnt any significant difference between Cell-VU chamber and CASA. Each
      laboratory can select its own proper method for manual or computer-aided
      analysis.

PMID- 16597037
TI  - [Correlation between premature ejaculation and redundant prepuce].
AB  - OBJECTIVE: To investigate the correlation between redundant prepuce and premature
      ejaculation. METHODS: Fifty-two cases suffering from premature ejaculation and
      redundant prepuce were treated with circumcision. They were asked to fill the
      investigating questionnaire about the changes of ejaculatory latent period,
      patients' and their wives' satisfaction with sexual life before and after the
      treatment. RESULTS: During 12 months after circumcision, 28 cases were cured and
      11 cases were efficacious. The curative rate was 54.9% and effective rate was
      76.5%. Twelve cases with no responding continued to be treated with routine
      methods, such as psychotherapy, daub narcotic to glans of penis and taking
      medicine to treat chronic prostatitis, which were used before circumcision but
      still no effects. During 18 months after circumcision, 4 cases were cured and 5
      cases were efficacious. CONCLUSION: Redundant prepuce had direct or indirect
      relationship with premature ejaculation. The circumcision is one of the effective
      methods to treat premature ejaculation.

PMID- 16597038
TI  - [Seminal parameter analysis in noninflammatory chronic prostatitis/chronic pelvic
      pain syndrome].
AB  - OBJECTIVE: To investigate seminal parameters in noninflammatory chronic
      prostatitis/chronic pelvic pain syndrome (CAP III B). METHODS: A total of 74
      consecutive cases of patients who had been diagnosed as CAP III B and 46 cases of
      controls were included in the study. Severity of symptoms in men with CAP III B
      was defined according to the NIH Chronic Prostatitis Symptom Index (NIH-CPSI).
      All of them underwent a 'four glass-test' including leukocyte determination in
      expressed prostatic secretions (EPS), voided urine after prostatic massage (VB3)
      and ejaculate semen followed by analysis according to WHO. The analysis included
      seminal volume, pH, duration of liquefaction, sperm density, vitality, motility(a
      + b) and morphology. Correlations between the duration or the severity of
      symptoms and spermiogram results in patients with CAP III B were assessed
      respectively. RESULTS: The CAP III B group and the control group differed
      significantly in ejaculate volume, duration of liquefaction and motility, while
      the remaining parameters did not differ significantly. The duration of chronic
      pelvic pain showed apparently positive correlationship with liquefaction time,
      while the symptom duration negatively correlated with sperm motility. The NIH
      CPSI score had no significant relationship with seminal volume, duration of
      liquefaction and sperm motility. CONCLUSION: Our results indicate that CAP III B
      can have a significant negative impact on sperm volume, liquefaction and
      motility. Our data also supports the results that the longer the duration of
      symptoms, the more influences on semen liquefaction and motility might be.

PMID- 16597039
TI  - [Expression and significance of metastasis-associated proteins in prostate cancer
      cell lines with different metastatic potentials].
AB  - OBJECTIVE: To observe the expression profiles between two metastasis-associated
      proteins in different prostate cancer cell lines and explore the molecular
      mechanisms of bone metastatic potentials. METHODS: Expressions of E-cadherin and
      vimentin in two prostate cancer cell lines (LNCaP and IA8) with different
      metastatic potentials were detected by Western blotting. RESULTS: There was
      remarkable difference in the expressions of E-cadherin and vimentin between the
      highly metastatic cell line and the lowly one. As one of the adhesion associated
      proteins, E-cadherin was detected with high level of expression in LNCaP cell
      line, which was well known as low metastatic potential. However, E-cadherin did
      not expressed in IA8 with high metastatic potential. And as one of the
      cytoskeleton proteins, vimentin expression was high in IA8, but not in LNCaP.
      CONCLUSION: There is definitely difference in the metastatic phenotypes (E
      cadherin and vimentin) among cell lines with different metastatic potentials. The
      expressions of E-cadherin and vimentin proteins may play important roles in
      promoting and inhibiting the metastasis of prostate cancer respectively, and may
      be considered to be valuable in evaluating the malignant degree, predictable
      metastasis and prognosis of prostate cancers.

PMID- 16597040
TI  - [Clinical application of alpha1 adrenoceptor antagonist Naftopidil to the
      treatment of chronic non-bacterial prostatitis].
AB  - OBJECTIVE: To study the efficacy and safety of alpha1 adrenoceptor antagonist
      Naftopidil in the treatment of chronic non-bacterial prostatitis. METHODS: An
      opened, self-controlled, multicentral clinical trial was conducted. One hundred
      and six cases of patients who had been diagnosed as chronic non-bacterial
      prostatitis (NBP) were treated with Naftopidil (25 mg once a day) for 4 weeks.
      The efficacy was evaluated by the NIH Chronic Prostatitis Symptom Index (NIH
      CPSI) and the WBC in the examination of prostatic secretion (EPS) after the
      treatment. RESULTS: After 4 weeks therapy, 105 cases were evaluable. After
      treatment, NIH-CPSI total score were averagely decreased 12.0 points (P <0.001),
      symptom score 7.9 points (P <0.001) and QOL score 4.1 points (P <0.001). There
      was a statistically significant difference in WBC count ([(15.2 +/- 15.1)/HP vs
      (9.5 +/- 12.0)/HP, P < 0.01] and max flow rate(MFR) [(19.2 +/- 4.8) ml/s vs (22.7
      +/- 4.9) ml/s, P < 0.01]. The total effective rate were 84.8% in the whole group.
      The clinical adverse rate was 3.81%, including 3 cases of mild dizziness and 1
      case of mild inappetence. CONCLUSION: alpha1 adrenoceptor antagonist Naftopidil
      is effective and safe for the treatment of chronic non-bacterial prostatitis.

PMID- 16597041
TI  - [The clinical treatment analysis of 176 cases of testicular germ cell tumor].
AB  - OBJECTIVE: To study the diagnosis, treatment and prognosis of testicular germ
      cell tumor. METHODS: From Oct. 1980 to Oct. 2000, 176 cases with testicular germ
      cell tumor treated in West China Hospital of Sichuan University were reported,
      and the clinical manifestations, diagnosis and treatment were analyzed
      retrospectively. RESULTS: There were 111 cases of testicular seminoma, 43 cases
      of testicular non-seminoma and 22 cases of mixture testicular germ cell tumor,
      and 46 out of 176 cases were complicated with cryptorchidism. The prognosis of
      patients was related to clinical stages, treatment and cryptorchidism.
      CONCLUSION: Since there is no significant difference in the oncological control
      effects in Stage I testicular seminoma, radiotherapy is not necessary after
      radical orchiectomy to avoid the side effects of radiation. The treatment of
      testicular non-seminoma, testicular seminoma in the stage II and III should
      combine the radical orchiectomy and radiotherapy. Early diagnosis and early
      treatment are the two most important factors affecting the survival of patients
      with testicular germ cell tumor.

PMID- 16597042
TI  - [Treatment of multiple condyloma acuminatum of the coronary sulcus with sleeve
      circumcision of prepuce and coronary sulcus skin (a report of 35 cases)].
AB  - OBJECTIVE: To evaluate the effectiveness of sleeve circumcision of prepuce and
      coronary sulcus skin in the treatment of patients with multiple condyloma
      acuminatum (CA) of coronary sulcus of penis. METHODS: In a randomized clinical
      control study, 35 patients were randomized to the treatment group and received
      sleeve circumcision of prepuce and coronary sulcus skin. 34 patients were
      randomized to the control group, received electric cauterization of verrucae plus
      the general circumcision. The recurrence of CA was evaluated in follow-up visit
      within three months after the treatment. RESULTS: The stitches were taken out
      10.2 days after operation in the treatment group, and 8.1 days in the control
      group. There were no complication in the treatment group, the average healing
      time of electric cauterization wound was 19.4 days in the control group. There
      was a statistically significant difference in the recurrence rate of CA between
      the treatment group and the control group (5.7% vs 26.5% , P <0.05). CONCLUSIONS:
      The sleeve circumcision of prepuce and coronary sulcus skin is more effective
      than electric cauterization of verrucae plus the general circumcision in the
      treatment of patients with multiple condyloma acuminatum of coronary sulcus of
      penis.

PMID- 16597043
TI  - [Comparison study on the diagnosis of erectile dysfunction with color Doppler
      ultrasonography and nocturnal electrobioimpedance volumetric assessment].
AB  - OBJECTIVE: To study the diagnostic value of color Doppler ultrasonography(CDUS)
      and nocturnal electrobioimpedance volumetric assessment (NEVA) in the assessment
      of erectile dysfunction (ED) and in differentiating the causes of ED. METHODS:
      CDUS and NEVA were performed in the 45 patients with ED. The patients were
      classified into 3 groups according to their results of CDUS, and compared all
      parameters of NEVA between each two groups, and then studied the correlation
      between CDUS and NEVA in the assessment of ED. RESULTS: In the non-vasculogenic
      ED group, 17 (94.4%) patients had normal nocturnal penile tumescence (NPT); and
      in contrast, there were 9(75.0%) and 8(72.7%) patients with abnormal NPT in the
      arteriogenic and venogenic ED groups, respectively. Except that the blood volume
      change of penis in the venogenic ED group was significantly lower than that in
      the non-vasculogenic ED group (P = 0.033), there were no significant difference
      in the other parameters of NEVA between each two groups. CONCLUSION: The results
      of NEVA are well correlated with the functions of artery and venous which were
      indicated by CDUS. NEVA can indicate the causes of ED to some extent.

PMID- 16597044
TI  - [Suprapubic transvesical prostatectomy with opening the prostatic cavity wide to
      treat benign prostatic hyperplasia of small volume].
AB  - OBJECTIVE: To evaluate therapeutic effects suprapubic transvesical prostatectomy
      with opening the prostatic cavity wide on BPH with small volume. METHODS: From
      Aug 1994 to Dec 2003, fifty-six patients with BPH of small volume were treated by
      suprapubic trans vesical prostatectomy with opening the prostatic cavity wide.
      RESULTS: Forty-two patients have been followed up for 3 approximately 22 months.
      Neither incontinence nor bladder outlet obstruction had been observed. IPSS, QOL
      and PVR decreased from (31.0 +/- 2.3) score, (4.5 +/- 0.4) score and (230.0 +/-
      30.0) ml (pre-operative) to (7.5 +/- 2.0) score, (1.5 +/- 0.5) score and
      disappearance (post-operative) respectively. All these differences were
      statistically significant (P <0.01). CONCLUSION: The procedure is effective for
      the patient with BPH of small volume.

PMID- 16597045
TI  - [Analysis of shape and retractability of the prepuce in 1,015 Chinese boys aged
      from 0 to 18 years old].
AB  - OBJECTIVE: To evaluate the characteristics of the preputial development in
      Chinese boys and indications as well as occasion of circumcision. METHODS: The
      shape and retractability of prepuce were evaluated in 1,015 Chinese boys from 0
      to 18 years old without heteroplasia of prepuce and penis. RESULTS: Ratio of
      children with phimosis decreases progressively with increasing age, from 64.09%
      in the first group (0 approximately 3 years old) to 7.66% in the fourth group (11
      approximately 18 years old). CONCLUSION: Phimosis and incomplete separation of
      the prepuce is normal in the neonate and infant. Prepuce will separate from the
      glans progressively till adolescence, so it's unnecessary to perform circumcision
      for them when without any complications.

PMID- 16597046
TI  - [Effects of senility on inducible nitric oxide synthase expression and cell
      apoptosis in rat penis].
AB  - OBJECTIVES: To investigate the effect of senility on inducible nitric oxide
      synthase (iNOS) expression and apoptosis in rat penis. METHODS: The rats were
      divided into three groups randomly: senescent, aged and young. Their penises were
      harvested to detect iNOS expression by immunohistochemistry and cell apoptosis
      rate by TUNEL, respectively. RESULTS: iNOS expression were 0.24 +/- 0.03, 0.17 +/
      0.02, 0.12 +/- 0.03 (relative A) and cell apoptosis rate were (1.41 +/- 0.78)%,
      (0.94 +/- 0.43)% and (0.50 +/- 0.23 )%, respectively, in the tissues of three
      groups. The differences among three groups were considerable significance (P
      <0.05). CONCLUSION: It maybe one of the mechanisms of erectile dysfunction in the
      aging male that senility causes the increase of iNOS expression and cell
      apoptosis.

PMID- 16597047
TI  - [Advances in the studies of morphological histology and imaging of benign
      prostatic hyperplasia].
AB  - Benign prostatic hyperplasia (BPH) is a familiar usually involves senile males.
      In recent 50 years, the incidence of BPH in China has been increasing. The
      morphological histology of hyperplastic prostate showed the volume enlarged and
      weight increase, and the hyperplastic part was mainly located in transitional
      zone. Researchers at home and abroad studied the tissue characteristics of
      hyperplastic prostate by routine and special staining coupled with computer
      assisted quantitative image analysis system, and found that the proliferation was
      mainly occurred in interstitial tissue of prostate. The imaging examination is an
      important assistant method to diagnose BPH. Especially, Transrectal ultrasound
      and magnetic resonance imaging can displayed hyperplastic prostate more clearly.

PMID- 16597048
TI  - [Advances in xenogeneic transplantation of spermatogonial stem cell and its
      bewilderment in clinical application].
AB  - Results from the transplantation of donor spermatogonia into xenogeneic recipient
      seminiferous tubules indicate that donor germ cells are capable of
      differentiating to form spermatozoa with morphological character of the donor
      species. With the advances in freezing, culturing in vitro and enriching germ
      cell populations, germ cell transplantation procedures have applications of
      paramount values in medicine, basic science and animal reproduction.
      Additionally, these techniques can serve as an alternative approach for gonadal
      protection and fertility preservation especially in patients accepting large dose
      of chemotherapy or radiotherapy. In this article we reviewed the recent advances
      in xenogeneic transplantation of spermatogonial stem cell and also analyzed the
      potential problems existing in its clinical application.

PMID- 16597049
TI  - [Neurotrophin and erectile dysfunction in diabetes].
AB  - Neurotrophins play significant roles in the development, differentiation and
      regeneration of many neurons. The abnormal changes of neurotrophins are one of
      the nosogenesis of diabetic peripheral neuropathy. Erectile dysfunction (ED) in
      diabetes is multifactorial and one of the most important causes is the injury of
      pelvic splanchnic nerves. Neurotrophins therapy shows exact effects on ED with
      pelvic splanchnic nerves injured. Recent researches indicates that the same
      treatment has the similar therapeutic effects on the ED animals with diabetes.
      Neurotrophins therapy develops a new way for us to cure the ED with diabetes.

PMID- 16597050
TI  - [Clinical observation of the treatment of male sexual dysfunction by
      yangjingjiaonang].
AB  - OBJECTIVE: To observe the therapeutic effect of Yangjingjiaonang on the treatment
      of male sexual dysfunction. METHODS: Two hundred and ten patients with male
      sexual dysfunction were divided into 2 groups, the treatment group orally
      delivered with Yangjingjiaonang, and the control group administrated with
      Wuziyanzongwan. The treatment lasted for 60 days, and the changes of sexual
      function were compared and measured by the total scores of IIEF. RESULTS: After
      taking orally drugs for 60 days, the total scores of IIEF-5 and the total scores
      of the questions 11 and 12 of IIEF in treatment group elevated from (11.26 +/- 2.
      72) score and (5.12 +/- 1.16) score to (16.84 +/- 3.12) score and (8.50 +/- 1.02)
      score, respectively, showing a significant improvement in the treatment group
      compared with the control (P <0.01). There was no significant difference for the
      treatment of premature ejaculation between the 2 groups. CONCLUSION:
      Yangjingjiaonang has been demonstrated to have apparent therapeutic effect on
      improving male sexual function.

PMID- 16597051
TI  - [Prevention is better than cure: a myth gone too far?].

PMID- 16597052
TI  - [Serum lipid and apolipoprotein ratios: do they add to cardiovascular risk
      assessment?].
AB  - The contribution of serum lipids to assessment of cardiovascular risk is based on
      single lipid measures. Non-speciallised doctors must therefore weigh the relative
      importance of different lipid fractions. Combining lipid analyses into ratios
      should improve risk prediction without increasing costs. A single ratio composed
      of positive and negative lipid factors simplifies interpretation for the non
      specialist. It can provide information on risk factors difficult to quantify by
      routine analyses and may better mirror the metabolic and clinical interactions
      between lipid fractions, Ratios are under-used in cardiovascular prevention, but
      can add to risk assessment.

PMID- 16597053
TI  - [Utility and limitations of the exercise stress test in medical outpatients: an
      update].
AB  - Exercise testing has remained a widely used test in clinical practice to detect
      and diagnose coronary artery disease, despite the possibility to use cardiac
      imaging. The indications and contraindications for exercise testing are well
      known. However, its limitations have to be kept in mind in order to adequately
      interpret its results. Although exercise testing allows also deriving prognostic
      data on cardiovascular morbidity and mortality, consensus papers do not recommend
      this test as a screening tool in cardiovascular prevention in asymptomatic
      subjects.

PMID- 16597054
TI  - [The role of aspirin in the primary prevention of cardiovascular disease].
AB  - For persons without cardiovascular disease, the benefit of aspirin in primary
      prevention has been controversial until the recent publication of several major
      randomized controlled trials. Since then, several medical societies recommend
      that clinicians discuss aspirin prevention with adults at high cardiovascular
      risk. Patients with low cardiovascular risk are unlikely to benefit from aspirin,
      as potential harms (hemorrhagic strokes, gastrointestinal bleedings) may outweigh
      benefits. Aspirin should be recommended in primary prevention only in patients
      with a 10-year cardiovascular risk > or = 10% or in diabetic patients aged > or =
      40 years with a concomitant cardiovascular risk factor, after assessing
      contraindications for aspirin and individual's preferences for the risks and
      benefits associated with aspirin.

PMID- 16597055
TI  - [Cardiovascular diseases: a target for prevention to thwart the effects of
      population aging].
AB  - The prevalence of cardiovascular diseases is high in the old age. These
      conditions have a negative impact on the quality of life and are associated with
      a high risk of disability. A marked increase in the number of affected
      individuals is likely, in coming decades, with population aging. Primary
      cardiovascular prevention, but also an early recognition of subclinical heart
      diseases and secondary and tertiary prevention will be of up most importance for
      individuals (quality of life) and for societies (burden of functional
      impairments) as the baby-boom generation reaches retirement age.

PMID- 16597056
TI  - [Evolution of cardiac risk factors management among patients aged 65 years and
      older with coronary artery disease].
AB  - The aim of this retrospective study was to compare the appropriateness of cardiac
      risk factors (CV-RF) management in a Swiss cardiac rehabilitation center. The
      comparison of the control of CV-RF among 342 patients with coronary artery
      disease (CHD) aged > or =65 years was improved. The CV-RF management has globally
      improved during the two periods of observation (1994-95 and 1999-2000).
      Nevertheless, according to the recommendations published between 1994 and 1999,
      an underuse of the cardioprotective agents was still observed. Using a
      standardized protocol for the management of CHD which allows the benchmarking
      among the network of cardiac rehabilitation centers network could increase the
      quality of care for such high risk patients.

PMID- 16597057
TI  - [Drug compliance in the elderly: determinants and support].
AB  - Drug adherence needs to be promoted in elderly patients taking multiple
      medications. Barriers to adherence are numerous and each barrier needs to be
      addressed specifically. Patients should be included in the therapeutic decision
      making process. Patient's life expectations and disease/treatment beliefs should
      be addressed. Healthcare practitioners should discuss the course of treatment
      with the patient proactively before any problem arises by using open-ended and
      informative questions. Functional and organizational barriers to adherence should
      be assessed throughout the treatment. A multidisciplinary approach to promote
      adherence is crucial and allows healthcare practitioners to combine specific
      skills (physician, pharmacist, nurse, etc.).

PMID- 16597058
TI  - [Short bowel syndrome: nutritional guidelines for the adult patient].
AB  - The short bowel is defined by the extended resection of the small intestine,
      leaving a maximum of 100 cm of healthy organ beyond the ligament of Treitz, with
      or without preservation of the colon. Nutritional management must be quick in
      order to optimize adaptation of the remaining intestine, therefore avoiding
      intestinal insufficiency. Consequent nutrition support such as long term enteral
      or parental nutrition is some times indispensable. Home enteral nutrition is
      relatively comfortable. Home parental nutrition somewhat complex, necessitates
      the creation of a strong home support group. This article addresses practitioners
      unfamiliar with clinical nutrition, directly faced with problems due to the short
      bowel in hospital (short and mean term phases) and in home settings (mean and
      long term phases).

PMID- 16597059
TI  - [Patient confidentiality].

PMID- 16597060
TI  - [New insight on the physiopathology of autoimmune diseases].

PMID- 16597061
TI  - [Chikungunya on Reunion Island, when politicians become interested in
      alphaviruses (2)].

PMID- 16597062
TI  - [Friday, February 24 2006, a few minutes of hysteria].

PMID- 16597063
TI  - [Subjectivity in physician-patient relations].

PMID- 16597064
TI  - [The law concerning human participants in research: the debate is launched].

PMID- 16597065
TI  - [Avian flu hysteria?].

PMID- 16597066
TI  - Food allergy: a practice parameter.

PMID- 16597067
TI  - On the cover. Live oak.

PMID- 16597068
TI  - Translating science to community action.

PMID- 16597069
TI  - Observations from TENOR: opportunities to improve asthma care.

PMID- 16597070
TI  - The impact of food allergy: the real "fear factor".

PMID- 16597071
TI  - Inhaled corticosteroid therapy in asthma: a potential problem with high doses.

PMID- 16597072
TI  - Optimal management of community-acquired acute bacterial rhinosinusitis: the
      allergist's perspective.
AB  - OBJECTIVES: To characterize the antibiotic resistance seen in community-acquired
      respiratory tract infections (RTIs) and determine which characteristics to look
      for in an antibiotic to improve clinical outcomes and decrease the potential for
      development of resistance. DATA SOURCES: Using MEDLINE, we performed a search of
      articles published from 1966 to 2004 to evaluate the current literature on the
      subject of antibiotic resistance and strategies to overcome it. Additional cited
      references, such as abstracts, were also identified. STUDY SELECTION: Relevant
      original research articles, reviews, and published abstracts were selected for
      inclusion in this review. RESULTS: Several factors were identified that should be
      considered when choosing empiric antibiotic therapy for community-acquired RTIs
      with the goal of improving clinical outcomes while minimizing the risk of
      resistance. These factors include spectrum of activity, bactericidal vs
      bacteriostatic activity, chemical structure, elimination half-life, and potency.
      CONCLUSIONS: The results of these studies support the use of targeted antibiotic
      agents that, based on structural and chemical properties, are optimized to have a
      low potential to induce resistance. This approach to antimicrobial therapy
      appears to be the most suitable for patients with acute bacterial rhinosinusitis
      and other community-acquired RTIs.

PMID- 16597073
TI  - Life-threatening asthma and anaphylaxis in schools: a treatment model for school
      based programs.
AB  - BACKGROUND: Pediatric asthma is the No. 1 chronic disease in childhood and is
      responsible for significant morbidity and mortality. In Nebraska, the number of
      asthma-related deaths is greater than the national average, and in 1998, 2
      students died of acute asthma attacks while attending school in the Omaha public
      schools (OPSs). In response, we designed and implemented a program to respond to
      this problem. OBJECTIVE: To implement and study a school-based program for the
      treatment of life-threatening asthma and anaphylaxis in the OPSs. METHODS: The
      Emergency Response to Life-Threatening Asthma or Systemic Allergic Reactions
      (Anaphylaxis) Protocol was designed and evaluated in 78 OPSs from 1998 to 2003.
      Nurses and school staff were trained in the protocol, which required the use of
      nebulized albuterol and/or intramuscular epinephrine in conjunction with an
      emergency response procedure. Outcomes were measured by improvement in acute care
      in schools and survival of students. RESULTS: In the 5 years of evaluation, 98
      students were treated successfully. One student died. Of those treated with the
      protocol, equal numbers had at school both asthma action plans (AAPs) and metered
      dose inhalers (MDIs), MDIs only, or neither AAPs nor MDIs. As a result of the
      program, there has been an increased awareness from parents, teachers, and
      physicians about the necessity of an emergency response program. In 2002, an
      outcome of the OPS program resulted in the formation of Attack on Asthma Nebraska
      to ensure that Nebraska schools have the education, training, and medications to
      respond to anyone experiencing a life-threatening asthma or anaphylaxis attack at
      school. The following year, a revised protocol was approved by the Nebraska State
      Board of Education for use in all Nebraska schools. CONCLUSIONS: Emergency
      response protocols provide protection for children while in school. This program
      should serve as a national model for other school-based programs for children and
      adolescents with asthma and anaphylaxis.

PMID- 16597074
TI  - Asthma in older adults: observations from the epidemiology and natural history of
      asthma: outcomes and treatment regimens (TENOR) study.
AB  - BACKGROUND: The Epidemiology and Natural History of Asthma: Outcomes and
      Treatment Regimens (TENOR) was a 3-year, multicenter, observational study of
      4,756 patients 6 years or older with severe or difficult-to-treat asthma by
      physician evaluation. More than 280 pulmonologist and allergist sites across the
      United States participated. OBJECTIVE: To compare health care utilization (HCU),
      medication use, asthma control, and quality of life (QoL) in older (> or =65
      years; n = 566) and younger (18-64 years; n = 2,912) adult patients in TENOR.
      METHODS: Patients had to be under a physician's care for at least 1 year and have
      high medication use or HCU in the past year. Heavy smokers (> or =30 pack-years)
      and patients with cystic fibrosis were excluded. RESULTS: Although older patients
      in TENOR had worse lung function as measured by decreased percent predicted
      forced expiratory volume in 1 second (FEV1) (P < .001), they had significantly
      lower HCU compared with younger patients. They also had higher use of inhaled
      corticosteroids and better QoL than younger patients. Older patients reported
      fewer problems controlling their asthma (P < .001) but reported worse
      communication with their physicians (P = .02). CONCLUSIONS: Older patients in
      TENOR appeared to do better than younger patients, despite having worse lung
      function. Older patients in TENOR may have received more aggressive care than
      older asthmatic patients in other studies, based on a higher use of inhaled and
      oral corticosteroids. Whether differences in treatment or disease influenced
      other physiologic or inflammatory outcomes that contribute to the disconnect
      between HCU and FEV1 awaits further study.

PMID- 16597075
TI  - The impact of food allergy on the daily activities of children and their
      families.
AB  - BACKGROUND: Food allergy affects a significant number of children, and its
      management requires considerable time and vigilance. OBJECTIVE: To determine the
      impact of food allergy on the daily activities of food allergic children and
      their families. METHODS: Caregivers of food allergic children from a university
      based allergy practice completed a questionnaire that evaluated their perception
      of the impact of their child's food allergy on family activities. RESULTS: Of the
      87 families who completed the study, more than 60% of caregivers reported that
      food allergy significantly affected meal preparation and 49% or more indicated
      that food allergy affected family social activities. Forty-one percent of parents
      reported a significant impact on their stress levels and 34% reported that food
      allergy had an impact on school attendance, with 10% choosing to home school
      their children because of food allergy. The number of food allergies had a
      significant impact on activity scores, but the existence of comorbid conditions
      such as asthma and atopic dermatitis did not significantly affect the results.
      CONCLUSIONS: Food allergy has a significant effect on activities of families of
      food allergic children. Further study is needed to determine more detailed
      effects of food allergy on parent-child interactions and development.

PMID- 16597076
TI  - A comparison of 2 extrafine hydrofluoroalkane-134a-beclomethasone formulations on
      methacholine hyperresponsiveness.
AB  - BACKGROUND: Small airways inflammation is a recognized pathologic component of
      asthma, and it is postulated that the observed airway-wall remodeling in small
      airways could be due to uncontrolled inflammation in airways that are not
      penetrated by conventional inhaled corticosteroids. Thus, extrafine particle
      formulations of inhaled corticosteroids are of clinical interest. OBJECTIVE: To
      compare 2 extrafine solution hydrofluoroalkane-134a formulations of
      beclomethasone dipropionate (Beclate and Qvar). METHODS: Fifteen asthmatic
      patients (mean +/- SEM forced expiratory volume in 1 second [FEV1], 2.62 +/- 0.21
      L; provocative concentration of methacholine causing a 20% decrease in FEV1
      [PC20], 1.06 +/- 0.58) were randomized to completion in a placebo-controlled,
      double-blind, crossover manner to receive Beclate or Qvar at doses of 100 or 400
      microg/d for 2 weeks, with a 1-week washout period before each randomized
      treatment. Methacholine hyperresponsiveness was the primary outcome measure.
      RESULTS: The 2 formulations were equivalent in terms of predefined equivalence
      limits of +/- 1 doubling dilution for PC20 at both doses: -0.25 (95% confidence
      interval [CI], -0.77 to 0.27) doubling dilution difference between the 100-microg
      doses and a 0.26 (95% CI, -0.29 to 0.82) doubling dilution difference between the
      400-microg doses for the difference between Beclate and Qvar, respectively. Both
      formulations, at either dose, produced a statistically significant (P < .05)
      reduction in mean exhaled nitric oxide levels: 400 microg/d of Beclate, 14.1 ppb
      (95% CI, 5.6 to 22.6 ppb); and 400 microg/d of Qvar, 14.2 ppb (95% CI, 6.0 to
      22.4 ppb). The higher doses produced a statistically significant (P < .05)
      reduction in early morning urinary cortisol-creatinine ratio (geometric mean fold
      suppression: Beclate, 1.48 [95% CI, 1.16 to 1.89]; and Qvar, 1.42 [95% CI, 1.12
      to 1.79]). Both formulations significantly improved peak expiratory flow, FEV1,
      and forced expiratory flow between 25% and 75% of forced vital capacity at the
      higher doses (P < .05). CONCLUSIONS: Beclate and Qvar were equivalent for all
      primary and secondary outcome measures.

PMID- 16597077
TI  - Association between response to decongestion testing and sensitizations and
      allergic inflammation.
AB  - BACKGROUND: Rhinomanometry is used to measure nasal airflow, which is frequently
      impaired in allergic rhinitis (AR). Decongestion testing consists of spraying an
      intranasal vasoconstrictor drug to evaluate recovery of nasal airflow. OBJECTIVE:
      To evaluate the relationships among type and number of sensitizations, nasal
      airflow recovery after topical vasoconstrictor drug use, and allergic
      inflammation. METHODS: A total of 123 patients (112 men and 11 women; mean +/- SD
      age, 22.9 +/- 5.7 years) were studied: 40 with perennial AR (PAR), 43 with mixed
      AR (MAR), and 40 with seasonal AR (SAR). Patients with anatomic nasal defects
      were excluded. Total symptom scores (including nasal itching, sneezing,
      rhinorrhea, and nasal obstruction), sensitizations, nasal eosinophils, and
      cytokines (including interleukin 4 [IL-4], IL-5, and interferon-gamma) were
      evaluated. Electronic rhinomanometry and decongestion testing were performed in
      all the patients. RESULTS: After administration of a topical nasal
      vasoconstrictor agent, mean nasal airflow significantly increased from 471 to 580
      mL/s (P < .001). In 12 patients (3 with PAR, 3 with MAR, and 6 with SAR), no
      increase was shown. Changes from baseline were different in the PAR, MAR, and SAR
      populations (PAR vs MAR, P < .001; PAR vs SAR, P < .001; and MAR vs SAR, P =
      .25). Type of sensitization (MAR, PAR, or SAR), concentration of eosinophils, and
      levels of IL-4, IL-5, and interferon-gamma were associated with nasal airflow
      recovery of at least 120 mL/s. CONCLUSIONS: This study provides the first
      evidence of a different response to decongestion testing taking into
      consideration the type of AR.

PMID- 16597078
TI  - Effects of long-term inhaled corticosteroids on adrenal function in patients with
      asthma.
AB  - BACKGROUND: Inhaled corticosteroids (ICSs) are effective asthma controllers, but
      long-term use could lead to adverse effects. OBJECTIVE: To examine adrenal
      responsiveness of patients with persistent asthma treated with long-term ICSs.
      METHODS: Morning plasma cortisol levels before and 30 minutes after
      adrenocorticotropic hormone (ACTH) (1 microg intravenously) stimulation were
      compared. Primary end points included mean prestimulation and poststimulation
      cortisol levels; secondary end points included morning cortisol level of 5
      microg/dL or less, post-ACTH stimulation cortisol level of 18 microg/dL or less,
      and/or a net change of 7 microg/dL or less from baseline. RESULTS: A total of 103
      asthmatic patients (29 in the triamcinolone acetonide group, 18 in the
      flunisolide group, 45 in the fluticasone propionate group, and 11 in the oral
      corticosteroids group [positive controls]) completed the study. Mean daily ICS
      doses and durations were as follows: triamcinolone acetonide: 448 microg for 36
      months; flunisolide: 1,181 microg for 41 months; and fluticasone propionate: 745
      microg for 19 months. Eleven of 30 patients taking high-dose ICSs (10 of 28
      taking fluticasone propionate and 1 of 2 taking flunisolide) had both low morning
      cortisol levels and abnormal post-ACTH stimulation cortisol levels. Few patients
      taking lower doses of any ICS had abnormal results. CONCLUSIONS: Patients who
      require long-term treatment with high-dose ICSs may have abnormal morning plasma
      cortisol levels and reduced responsiveness to ACTH stimulation. Careful
      monitoring of adrenal function should be considered in such patients.

PMID- 16597080
TI  - Noninvasive positive pressure ventilation for the treatment of status asthmaticus
      in children.
AB  - BACKGROUND: Noninvasive positive pressure ventilation (NPPV) has been used safely
      and effectively to improve gas exchange and to treat respiratory failure in a
      variety of disease states. Although this technique has some benefits in the
      treatment of status asthmaticus in adults, the use of NPPV in pediatric patients
      with asthma has not been described. OBJECTIVE: To describe the use of NPPV in the
      treatment of pediatric status asthmaticus. METHODS: Retrospective review of
      children admitted to the intensive care unit with asthma who received NPPV as
      part of their treatment between October 2002 and April 2004. Before and after
      initiation of NPPV, data were collected regarding degree of respiratory
      dysfunction. RESULTS: Of seventy-nine children admitted to the intensive care
      unit during the study period for treatment of status asthmaticus, 5 children
      (mean +/- SD age, 9.6 +/- 4.2 years) were treated with NPPV. Four of the 5
      children were morbidly obese, with a mean +/- SD body mass index of 32 +/- 5.
      There was a statistically significant improvement in respiratory rate (43 +/- 20
      vs 31 +/- 12/min, P = .03) and Modified Pulmonary Index Score (13.4 +/- 1.8 vs
      11.4 +/- 1.5, P = .03) after initiation of NPPV. The mean +/- SD duration of
      therapy was 33.2 +/- 23.9 hours, and children tolerated this therapy well,
      requiring little or no anxiolytics. CONCLUSIONS: NPPV was well tolerated in this
      series of children with status asthmaticus and can improve subjective and
      objective measures of respiratory dysfunction. NPPV may be a useful adjunct in
      the treatment of status asthmaticus in children.

PMID- 16597079
TI  - Prenatal, perinatal, and heritable influences on cord blood immune responses.
AB  - BACKGROUND: Maternal and perinatal environmental exposures, as well as inherited
      factors, may influence neonatal immune responses. OBJECTIVE: To determine
      relations of maternal and perinatal exposures to antigen-specific cord blood
      lymphoproliferative responses. METHODS: In 427 newborns from a Boston
      pregnancy/birth cohort, lymphoproliferative responses in cord blood mononuclear
      cells to stimulation with cockroach (Bla g 2), house dust mite (Der f 1),
      ovalbumin, and mitogen phytohemagglutinin were measured as stimulation index
      (SI). We used the Wilcoxon rank sum and chi2 tests to evaluate predictors of
      ovalbumin SI as a continuous ranked or dichotomous outcome. We used t test and
      Spearman correlation for univariate testing and linear regression to evaluate
      predictors of natural log-transformed Bla g 2, Der f 1, and phytohemagglutinin
      SI. Logistic multivariate regression was applied to evaluate predictors of Bla g
      2, Der f 1, and phytohemagglutinin SI dichotomized at 2 or at the median for
      phytohemagglutinin. RESULTS: Maternal smoking during pregnancy, inadequate or
      excessive maternal weight gain during pregnancy, neonate black race/ethnicity
      (compared with white), and Apgar score less than 8 were each independently
      associated with increased cord blood mononuclear cell proliferative responses to
      stimulation with Bla g 2 and/or Der f 1. Maternal history of asthma was
      associated only with increased lymphoproliferative response to ovalbumin
      stimulation. CONCLUSIONS: Distinct fetal and perinatal exposures and black
      race/ethnicity may be associated with increased cord blood lymphoproliferative
      responses. The implications of these findings for future development of allergy
      or asthma are, as yet, unknown.

PMID- 16597081
TI  - Desloratadine therapy for symptoms associated with perennial allergic rhinitis.
AB  - BACKGROUND: Perennial allergic rhinitis (PAR) has a substantial negative social
      and economic impact. Recent studies emphasize the potential seriousness of PAR
      and the need for improved treatment of this condition. OBJECTIVE: To confirm the
      efficacy and safety of the H1-antihistamine desloratadine in reducing the
      symptoms of PAR in a randomized, double-blind, placebo-controlled trial. METHODS:
      Patients with PAR (N = 1,179) from 67 US/international centers received
      desloratadine, 5 mg once daily, or identical placebo tablets. The primary
      efficacy measure was the change from baseline to week 4 in average morning and
      evening reflective total symptom scores (TSSs). Secondary end points included
      changes from baseline in total nasal and nonnasal symptom scores and peak nasal
      inspiratory flow (PNIF) rates. RESULTS: Desloratadine was significantly more
      effective than placebo in reducing morning and evening reflective TSSs for each
      week and during weeks 1 through 4 (P = .001). Mean changes in TSSs during the 4
      week study were -3.9 (26.6% reduction) and -3.2 (22.3% reduction) for the
      desloratadine and placebo groups, respectively (P = .001, desloratadine vs
      placebo). With desloratadine therapy, significant improvements were also seen in
      secondary efficacy end points compared with placebo use (total nasal and nonnasal
      symptom scores: P < or = .04). Improvements in mean morning PNIF were
      significantly greater in the desloratadine-treated group than in the placebo
      group (P = .03). CONCLUSIONS: These results confirm and extend previous findings
      that desloratadine is safe and is associated with a statistically significant
      reduction in nasal and nonnasal symptoms in patients with PAR. Objective nasal
      airflow, evaluated by PNIF, was statistically significantly improved after
      desloratadine treatment.

PMID- 16597082
TI  - The role of major olive pollen allergens Ole e 1, Ole e 9, and Ole e 10 on mice
      sensitization.
AB  - BACKGROUND: Olive pollen is an important cause of allergy in Mediterranean
      countries. To date, 10 allergens (Ole e 1 to Ole e 10) have been isolated and
      characterized. Animal models of olive pollen allergy are suitable tools for
      testing the efficacy and safety of new forms of immunotherapy. OBJECTIVES: To
      characterize the immune response in mice sensitized with olive pollen extract and
      to compare it with that of allergic patients. METHODS: BALB/c mice were
      sensitized by 4 intraperitoneal injections of olive pollen extract in aluminum
      hydroxide. The allergic state was proved by measuring serum specific IgG1 and
      total IgE antibody levels. The IgG1 responses to olive pollen allergens were
      assayed by immunoblotting and enzyme-linked immunosorbent assay. Competition
      experiments between human IgE and mouse IgG1 binding to olive pollen allergens
      were performed. RESULTS: Sensitization with olive pollen extract induced high
      levels of specific IgG1 and total IgE in all tested animals. Immunoblotting
      experiments showed that the mouse IgG1 binding pattern to pollen extract was
      complex and heterogeneous, as occurs with human IgE. High IgG1 antibody levels to
      the major olive pollen allergens described for humans were detected in serum
      samples from sensitized mice, whereas minor olive pollen allergens induced no
      significant IgG1 response. Coincubation of mouse serum samples with a cocktail of
      Ole e 1, Ole e 9, and Ole e 10 resulted in a significant decrease (60%) in IgG1
      binding to olive pollen extract. Specific mouse IgG1 strongly inhibited human IgE
      binding to olive pollen allergens. CONCLUSIONS: This mouse model of olive pollen
      sensitization mimics immunologic features of human pollinosis and could be a
      useful tool for designing novel forms of immunotherapy for olive pollen allergy
      based on allergen cocktails.

PMID- 16597083
TI  - Development of a preliminary questionnaire to assess parental response to
      children's food allergies.
AB  - BACKGROUND: Food allergy affects up to 8% of children. Unintentional exposure may
      result in minor to potentially fatal episodes. Management of allergies depends on
      strict allergen avoidance and emergency preparedness. The demands of allergy
      management and concerns for the child's safety may place parents at risk of
      developing emotional distress or difficulties in coping. OBJECTIVE: To develop a
      brief condition-specific measure to evaluate parental adjustment to and coping
      with children's food allergy. METHODS: A total of 221 parents of children 18 year
      or younger with food allergy were recruited from a private allergy practice and
      local food allergy support groups. Parents completed an 18-item questionnaire,
      the Food Allergy Parent Questionnaire (FAPQ), that assessed parental coping with
      a child's food allergy and questions related to their child's food allergy
      diagnosis and course. RESULTS: Factor analysis of the items on the FAPQ suggested
      4 factors that accounted for 53.6% of the variance: parental anxiety/distress,
      psychosocial impact of allergies, parental coping/competence, and family support.
      Medical variables (greater number of food allergies, positive history of
      anaphylaxis) were associated with higher scores on the anxiety/distress and
      psychosocial impact subscales. Internal consistency was good for the
      anxiety/distress and psychosocial impact subscales (Cronbach alpha = .80 and .77,
      respectively) but lower for the parental coping/competence and family support
      subscales (alpha = .57 and .32, respectively). CONCLUSIONS: Although further
      psychometric data for the FAPQ is needed, preliminary findings suggest that the
      measure may be useful in screening for parental anxiety, perceived impact of food
      allergies, level of family support, and coping skills.

PMID- 16597084
TI  - Unusual cause of cough and wheeze in a 10-year-old child.

PMID- 16597085
TI  - A 59-year-old woman with fever, cough, and eosinophilia.

PMID- 16597086
TI  - Periorbital swelling and nasal congestion in a 31-year-old man.

PMID- 16597087
TI  - Occupational asthma related to aescin inhalation.
AB  - BACKGROUND: More than 400 agents are recognized as causes of occupational asthma,
      a work-related disease that can be induced by an immunologic or a nonimmunologic
      mechanism. OBJECTIVE: To describe a 57-year-old man employed in the
      pharmaceutical industry who developed bronchial asthma while working with
      products such as Plantago ovata and aescin, an active ingredient with anti
      inflammatory and venotonic properties. METHODS: Various tests were performed,
      including radiography, total serum IgE titer measurements, skin tests against
      common pneumoallergens and Plantago species, pulmonary function studies, a
      methacholine test, and specific inhalation challenge with P. ovata and aescin.
      RESULTS: The results of these tests, including specific inhalation challenge,
      confirmed the diagnosis of occupational asthma due to aescin exposure, whereas
      the results of specific challenge with P. ovata, a known cause of occupational
      asthma, were negative. CONCLUSIONS: Aescin may represent a new causative agent of
      occupational asthma in personnel working in the pharmaceutical industry. The
      mechanism by which aescin can produce asthma is unknown, but analysis of the
      characteristics of our patient suggests a non-IgE immunologic mechanism, although
      an irritative mechanism secondary to long-term low-level exposure to aescin, a
      possible irritant, cannot be ruled out.

PMID- 16597088
TI  - Anaphylaxis to isosulfan blue and cross-reactivity to patent blue V: case report
      and review of the nomenclature of vital blue dyes.
AB  - BACKGROUND: Blue dyes used for lymphatic mapping in sentinel lymph node biopsy
      cause intraoperative anaphylactic reactions in up to 2.7% of patients. With
      increasing implementation of this technique, the incidence of anaphylaxis to
      these dyes can be expected to increase. In the literature, the chemically often
      unrelated and inconsistently designated dyes have been confused, adding to other
      inconsistencies in the nomenclature. OBJECTIVE: To demonstrate the nomenclature,
      chemical and physiologic differences, and allergenicity of the various blue dyes
      used in a medical context. METHODS: We describe a patient with an intraoperative
      grade IV anaphylactic reaction to isosulfan blue. Immediate-type hypersensitivity
      was proved by positive skin test reactions and CD63 expression to isosulfan blue
      and cross-reactivity to patent blue V. RESULTS: A review of the literature
      clarified the exact nomenclature of the blue dyes and the possible pitfalls of
      confusing nomenclature in the context of structurally closely related dyes with
      different allergenic properties. For the detection of type I hypersensitivity,
      intracutaneous tests are valuable tools. An IgE-mediated mechanism has been shown
      recently. In most cases, sensitization exists without known previous exposure in
      a medical context. This may be due to the widespread use of such dyes in objects
      of everyday life. Preoperative antiallergic medication use does not prevent
      anaphylactic reactions but apparently reduces their severity. CONCLUSION: For
      better comparison and precision, the Chemical Abstracts Service number of the
      respective dye should always be given.

PMID- 16597090
TI  - Pain treatment in ambulatory medical practice.

PMID- 16597091
TI  - The MRI appearance of Paget's disease of the nipple: images from a single case.

PMID- 16597092
TI  - An opinion regarding musculoskeletal pain and opiates.

PMID- 16597093
TI  - Targeting the epidermal growth factor receptor (EGFR)--a new therapeutic option
      in oncology?
AB  - The epidermal growth factor receptor (EGFR) is commonly overexpressed in a
      variety of solid tumours, and clinical trials indicate that this antigen has
      important roles in cancer aetiology and progression. EGFR thus provides a
      rational target for cancer therapies and a number of strategies influencing this
      receptor, and its downstream signal cascades, including monoclonal antibodies,
      tyrosine-kinase inhibitors, antisense oligonucleotides inhibiting EGFR synthesis
      and antibody-based immunoconjugates, have been evaluated. In particular,
      monoclonal antibodies targeting the receptor's extracellular domain and small
      molecules blocking tyrosine-kinase activation intracellularly have already shown
      some activity in clinical phase I-III trials. These two major classes of anti
      EGFR therapeutics will be the main topic of this review. In the case of tyrosine
      kinase inhibitors, amplification, high polysomy of the EGFR gene, high protein
      expression and mutations of the receptor were found to be significantly
      associated with better response to such treatment. However, many questions remain
      unanswered and future issues in the development of EGFR inhibitors will include
      the identification of biological predictors of response, combination with other
      therapies and also their use in earlier stages of cancer.

PMID- 16597094
TI  - Feasibility of mobile cardiopulmonary exercise testing.
AB  - QUESTIONS UNDER STUDY: Evaluation of cardiopulmonary capacity and work ability is
      often done by cardiopulmonary exercise testing under laboratory conditions.
      Mobile CPET devices allow measurements under specific real-life conditions, i.e.:
      at the patient's workplace. We investigated the feasibility and validity of
      mobile CPET in healthy controls. METHOD: We compared oxygen uptake measured by
      mobile CPET (MCPET) with that by standard CPET (LCPET), and we compared oxygen
      uptake with markers of self-reported physical exhaustion. Twenty-two healthy
      subjects (15 male, 21-49 years) underwent LCPET and 6 outdoors 12-min running
      tests (MCPETs) at different intensities. Physical exhaustion and the time they
      could continue exercising (T(EX)) was reported for each level. Standard
      descriptive statistics were applied. RESULTS: Of 132 MCPETs, performed in 22
      subjects, 128 (97%) were of suitable quality. The facemask was well tolerated and
      nobody felt uncomfortable at any time. On average VO2 [peak] was 21% (SD 9%)
      higher with MCPET compared to LCPET (median 3.60, range [2.22, 5.14] versus
      median 2.63, range [1.67, 4.16] L*min(-1)), but showed a strong correlation (r2 =
      0.90). MCPET-VO2 at steady state correlated with subjectively rated physical
      exhaustion, and with TEX. CONCLUSIONS: Out-of-laboratory MCPET was feasible,
      correlated with parameters of standard CPET, and correlated with markers of
      physical exhaustion. After validation in patients, MCPET could be used for a
      rational evaluation of cardiopulmonary capacity and work ability in selected
      patients.

PMID- 16597095
TI  - Experimental study of recombinant eukaryotic expression vector of human eNOS in
      ECV304.
AB  - BACKGROUND AND PURPOSE: Gene transfer with recombinant non-viral vectors encoding
      vasodilator proteins, such as endothelial nitric oxide synthase (eNOS), maybe a
      preferential choice in gene therapy of artery restenosis following angioplasty,
      stent or anastomosis. However, the transfection rate of a non-viral vector, the
      harmful effects of eNOS transfection on endothelial cells (EC) and the control
      release of nitric oxide (NO) have been controversial. We designed the eukaryotic
      expression vector pcDNA3.1-eNOS to study the regulated expression of eNOS (in the
      presence of various chemical agents) and to evaluate the exogenous NO effect on
      EC proliferation in vitro. METHODS: The full-length human eNOS cDNA was inserted
      into the EcoRI cloning site of the pcDNA3.1 expression plasmid and the eNOS
      direction was tested by restriction enzyme digestion with XhoI to construct
      recombinant pcDNA3.1-eNOS. After co-transfection of pcDNA3.1-eNOS with pcDNA3.0
      EGFP mediated by cationic liposomes into Human umbilical vein endothelial cells
      (ECV304), the transfection rate and the effect on ECV304 proliferation were
      calculated by fluorescence microscopy and flowcytometry. eNOS mRNA and protein
      were detected by reverse transcription-PCR (RT-PCR) and immunofluorescence,
      respectively. The eNOS activity, NO release and changes of the relevant cells
      growth curve were assessed after treating the transfected cells with four
      independent factors including ie Ca2+, L-arginine (L-Arg), Ethylene Diamine
      Tetraacetic Acid (EDTA) and N-nitro-L-arginine methylester (L-NAME). In addition,
      we examined the non-transfected cells status by isolated sodium nitroprusside
      (SNP) treatment. RESULT: eNOS cDNA was inserted into pcDNA3.1 in the proper
      direction. RT-PCR analysis showed that pcDNA3.1-eNOS transfected cells could
      express eNOS mRNA. The rate of eNOS transfection was 39.6 +/- 3.4%.
      Immunofluorescence staining displayed that subcellular localisation of eNOS was
      most prominent in plasma membrane and perinuclear regions of the cell. The eNOS
      activity of eNOS transfected cells had not increased significantly, whereas, in
      the presence of Ca2+, L-Arg, EDTA, and L-NAME, the eNOS activity was 96.98 +/-
      13.47, 32.57 +/- 6.39, 11.63 +/- 3.02, 15.56 L 7.34 U/ml respectively and the NO
      level was 55.34 +/- 11.19, 9.43 +/- 4.51, 2.63 +/- 1.41, 3.73 +/- 1.65 mmol/L,
      respectively. Meanwhile, the growth curves of EC shifted. SNP also had obvious
      growth-inhibiting effects on the cells. Together, the ECV304 growth curve went
      downward in a NO concentration-dependent manner. CONCLUSION: Eukaryotic
      expression vector pcDNA3.1-eNOS was constructed successfully with the ability to
      express human eNOS mRNA and protein in EC effectively. The activity of eNOS in EC
      could be regulated by certain exogenous factors. Ca2+ was an important factor
      promoting NO release and excess NO had a cytotoxic effect on EC in vitro.
      Controlled release of NO in vivo and polygenic measurements might be considered
      in more clinical gene therapy studies.

PMID- 16597096
TI  - Institutional conditions and individual experiences in the career-entry period of
      Swiss medical residents--a qualitative study.
AB  - BACKGROUND AND OBJECTIVES: The study investigated first-year residents' career
      entry experiences according to gender, clinical field and type of training
      hospital. In addition to quantitatively assessed workplace experiences, this
      paper reports qualitative data on institutional conditions as well as
      interpersonal and individual experiences encountered by junior physicians during
      their first year of residency. METHODS: The present study is part of the
      longitudinal Swiss physicians' career development study. After their first year
      of residency, participants were interviewed for the second time. The qualitative
      data of this second assessment are reported in this paper. A total of 1861 terms
      were given by 342 junior physicians working in the two main clinical fields
      (internal medicine and surgical fields) with regard to positive and negative
      experiences in the career entry period. The answers were assigned to 12
      categories (according to Mayring's content analysis). These categories were then
      allocated to three superordinate subject areas: Institutional conditions,
      Interpersonal experiences, and Individual experiences. RESULTS: Institutional
      conditions accounted for 17% of all entries, with negative experiences in
      particular, high workload - predominating. Within Interpersonal workplace
      experiences (41% of all responses), relationship experiences accounted for the
      largest proportion of all statements (25.7%), which were mainly positive.
      Individual experiences (42%) were assessed both positively (professional
      competence, learning, responsibility, and pleasure) and negatively (working under
      pressure and curtailment of one's private life). Female and male residents
      reported similar workplace experiences. Residents in surgical fields more often
      complained of a lack of professional support than those in internal medicine.
      Physicians working in university or big county hospitals had more negative
      experiences with regard to teaching than residents at smaller hospitals.
      CONCLUSION: The junior physicians' career-entry experiences indicated that a
      genuine concept of education and training would greatly improve their workplace
      experiences. Furthermore, senior physicians should bear in mind that they are
      important role models for the junior staff.

PMID- 16597097
TI  - [I guidelines of prevention of atherosclerosis in childhood and adolescence].

PMID- 16597098
TI  - Torsional steering controls the stereoselectivity of epoxidation in the
      guanacastepene a synthesis.
AB  - [reaction: see text] The stereoselectivity of the key epoxidation step in the
      synthesis of guanacastepene A is shown to be controlled by torsional steering. In
      this particular epoxidation reaction, the transition structure energetic
      difference is enhanced by the great asynchronicity of the forming C-O bonds that
      intensifies the torsional interactions.

PMID- 16597099
TI  - "Achiral" benzophenone ligand for highly enantioselective Ru catalysts in ketone
      hydrogenation.
AB  - [reaction: see text] The chirality of an "achiral" benzophenone-based complex can
      be controlled. The benzophenone-based complex thus controlled affords high
      enantioselectivity in the catalytic asymmetric ketone hydrogenation (up to 99%
      ee, >99% yield).

PMID- 16597101
TI  - Unprecedented SnCl2-mediated cyclization of nitro arenes via N-N bond formation.
AB  - [reaction: see text] A mild, efficient, one-pot protocol for the cyclization of
      nitro-aryl substrates using SnCl(2) has been described. The mechanistic course of
      the reaction suggests the involvement of a hydroxylamine intermediate leading to
      an intramolecular cyclization via N-N bond formation. The versatility of the
      methodology has been demonstrated by using two nitro-aryl substrates derived from
      dihydroisoquinolines and dihydro-beta-carbolines. The intramolecular cyclization
      led to the formation of indazoles in high yields and purities.

PMID- 16597100
TI  - Unexpected ring-opening reactions of aziridines with aldehydes catalyzed by
      nucleophilic carbenes under aerobic conditions.
AB  - [reaction: see text] The chemoselective ring opening of N-tosyl aziridines with
      aldehydes catalyzed by an N-heterocyclic carbene was investigated under aerobic
      conditions. Unexpected carboxylates of 1,2-amino alcohols from the corresponding
      aldehydes, rather than the acyl anion ring-opened beta-amino ketones, were
      exclusively obtained. A plausible mechanism for this unprecedented carbene
      mediated reaction was also proposed.

PMID- 16597103
TI  - Total synthesis of ent-dihydrocorynantheol by using a proline-catalyzed
      asymmetric addition reaction.
AB  - [reaction: see text] 9-Tosyl-3,4-dihydro-beta-carboline reacted with 3-ethyl-3
      buten-2-one in the presence of (S)-proline to give (3R,12bR)-3-ethyl-12-tosyl
      3,4,6,7,8,9,10,11,12,12b-decahydro-1H-indolo[2,3-a]quinolizin-2-one in complete
      enantio- and diastereoselectivity. The compound thus obtained was readily
      transformed to ent-dihydrocorynantheol in three steps.

PMID- 16597102
TI  - Gold(III) Salen complex-catalyzed synthesis of propargylamines via a three
      component coupling reaction.
AB  - [reaction: see text] Propargylamines have been synthesized by a gold(III) salen
      complex-catalyzed three-component coupling reaction of aldehydes, amines, and
      alkynes in water in excellent yields at 40 degrees C. With chiral prolinol
      derivatives as the amine component, excellent diastereoselectivities (up to 99:1)
      have been attained. This coupling reaction has been applied to the synthesis of
      propargylamine-modified artemisinin derivatives with the delicate endoperoxide
      moieties remaining intact. Cytotoxicities with IC(50) values up to 1.1 microM
      against a human hepatocellular carcinoma cell line (HepG2) were exhibited by
      these artemisinin derivatives.

PMID- 16597104
TI  - Regioselective dicouplings: application to differentially substituted pyrroles.
AB  - [reaction: see text] In an effort to develop a more concise route to
      differentially substituted pyrroles (such as that found in the lamellarins), a
      completely regioselective one-pot double Suzuki coupling has been discovered. The
      key feature is the use of a ligand-free palladium catalyst under optimized
      conditions, which results only in coupling of the C5 bromide. At this point,
      addition of a second boronic acid and a phosphine ligand enables coupling at the
      remaining C4 bromide.

PMID- 16597105
TI  - Nanomaterials of triazine-based dendrons: convergent synthesis and their physical
      studies.
AB  - [structure: see text] Without employing protection and deprotection processes,
      two series of triazine-based dendrons were efficiently prepared by a convergent
      method and fully characterized; their physical properties, including acidic,
      thermal, electrical, and optical stabilities were also studied.

PMID- 16597106
TI  - Synthesis and properties of a new fluorescent bicyclic 4-N-carbamoyldeoxycytidine
      derivative.
AB  - [reaction: see text] A bicyclic 4-N-carbamoyldeoxycytidine derivative (1,
      dC(hpp)) geometrically locked was synthesized as a new fluorescent nucleobase.
      The hybridization properties of oligodeoxynucleotides containing dC(hpp) were
      investigated by use of T(m) analysis. It was found that dC(hpp) forms stable base
      pairs not only with the complementary guanine base, but also with the adenine
      base. Interestingly, the fluorescence of dC(hpp) was suppressed only when a
      dC(hpp)-dG base pair was formed.

PMID- 16597107
TI  - A new rhodamine-based chemosensor exhibiting selective Fe(III)-amplified
      fluorescence.
AB  - [structure: see text] A new fluorescent probe 3 was synthesized, and it exhibited
      high selectivity for Fe(III) over other commonly coexistent metal ions in both
      ethanol and water. Upon the addition of Fe(III), the spirocyclic ring of 3 was
      opened and a significant enhancement of visible color and fluorescence in the
      range of 500-600 nm was observed.

PMID- 16597109
TI  - Alkenenitriles: Zn-Cu promoted conjugate additions of alkyl iodides in water.
AB  - [reaction: see text] A new silica-supported zinc-copper matrix dramatically
      promotes conjugate additions of alkyl iodides to alkenenitriles in water. Acyclic
      and cyclic nitriles react with functionalized alkyl iodides, overcoming the
      previous difficulty of performing conjugate additions to disubstituted
      alkenenitriles with nonstabilized carbon nucleophiles. Conjugate additions with
      omega-chloroalkyl iodides generate cyclic nitriles primed for cyclization,
      collectively providing one of the few annulation methods for cyclic
      alkenenitriles.

PMID- 16597108
TI  - High-yield synthesis of fluorinated benzothiazolyl sulfones: general synthons for
      fluoro-julia olefinations.
AB  - [reaction: see text] General, high-yield tandem electrophilic fluorination and
      modified Julia olefination for the synthesis of fluoro olefins is reported. A
      series of alpha-fluoro 1,3-benzothiazol-2-yl sulfone-based synthons were
      synthesized via deprotonation-fluorination. Of critical importance for high-yield
      fluorinations were heterogeneous reaction conditions, as under homogeneous
      conditions only starting sulfones were recovered. The alpha-fluoro 1,3
      benzothiazol-2-yl sulfones so obtained were subjected to condensations with a
      variety of aldehydes and ketones to afford high yields of regiospecifically
      fluorinated olefins.

PMID- 16597110
TI  - Novel C3v-symmetrical N7-Hexahomotriazacalix[3]cryptand: a highly efficient
      receptor for halide anions.
AB  - [structure: see text] We report the synthesis of a novel C(3)(v)()-symmetrical
      N(7)-hexahomotriazacalix[3]cryptand (1). Compound 1 was shown to be in a fixed
      cone conformation by (1)H NMR spectroscopy and X-ray single-crystal structure
      determination. Complexation studies showed that 1 is a selective receptor for
      halide ions. The effects of zinc metal cation on the receptor (1-Zn(2+)) upon
      anion recognition are also shown.

PMID- 16597112
TI  - Total synthesis of the marine alkaloid (+/-)-lepadiformine via a radical
      carboazidation.
AB  - [reaction: see text] The total synthesis of lepadiformine has been achieved in 10
      steps and 15% overall yield from cyclohexanone. The amino-substituted quaternary
      carbon center is created through a radical carboazidation reaction. The tricyclic
      core of lepadiformine is built via an efficient hydrogenation process, involving
      reduction of the azide and intramolecular reductive amination of a ketone,
      followed by lactamization of the intermediate gamma-aminoester. The hydroxymethyl
      side chain is introduced according to a modified Takahata procedure after
      conversion of the lactam into a thiolactam.

PMID- 16597111
TI  - De novo chiral amino alcohols in catalyzing asymmetric additions to aryl
      aldehydes.
AB  - [reaction: see text] A de novo structural class of chiral amino alcohol catalysts
      has been identified through a synergistic effort combining novel architectures
      from [4 + 3] cycloadditions and quantum mechanical interaction field predictions
      that closely match subsequent experimental measurements.

PMID- 16597113
TI  - Synthesis of the norjatrophane diterpene (-)-15-acetyl-3-propionyl- 17
      norcharaciol.
AB  - [reaction: see text] A scalable enantioselective synthesis of the nonnatural 17
      norjatrophane diterpene 3-propionyl-15-acetyl-17-norcharaciol is described. Key
      C/C-connecting transformations are an Evans aldol reaction, an intramolecular
      carbonyl ene reaction, a Horner-Wadsworth-Emmons olefination, and a ring-closing
      metathesis for the formation of a 12-membered carbacycle.

PMID- 16597114
TI  - Benzotriazole complexes with amines and phenol: cooperativity mediated by
      induction effects in the crystal state.
AB  - [structure: see text] Benzotriazole forms complexes of different stoichiometries
      with amines and phenols. Four of them have been characterized by single-crystal X
      ray diffraction. The trends of donor-acceptor hydrogen-bond distances between
      corresponding molecular entities in the different complexes are related to
      induction-mediated cooperativity effects.

PMID- 16597115
TI  - Chemically modified dansyl probes: a fluorescent diagnostic for ion and proton
      detection in solution and in polymers.
AB  - [reaction: see text] The fluorescence emission intensity of the dansyl group is
      significantly diminished upon appending an ethyldimethylamino group to the N1
      nitrogen substituent. Addition of acids and metal ions (i.e., Zn(2+)) to
      solutions of trimethylethylenediamine naphthalene sulfonamide (trinsyl) 2
      produces a >25-fold increase in fluorescence intensity. Trinsyl probe 2 has been
      used as a diagnostic for the diffusion of protons and metal ions in a network
      polymer as well as an optical reporter for the glass transition temperature.

PMID- 16597116
TI  - Synthesis of homopolymer containing diphenyl end-capped oligothiophene co
      oligomer unit in the side chain.
AB  - [reaction: see text] A new polymer with the diphenyl end-capped oligothiophene co
      oligomer unit in the side chain was obtained by the ROMP method. The polymer
      showed good photophysical characteristics, thermal stability, and film-forming
      properties. A photovoltaic cell fabricated from this polymer showed relatively
      large open-circuit voltage (V(OC) = 0.7 V), moderate short-circuit current (I(SC)
      = 0.7 microA/cm(2)), and excellent device stability under ambient conditions.

PMID- 16597117
TI  - Higher affinity quadruply hydrogen-bonded complexation with 7-deazaguanine urea.
AB  - [structure: see text] UG forms a highly stable quadruply hydrogen-bonded
      heterocomplex with DAN, but the fidelity of the complex is lowered somewhat by
      the Hoogsteen-side oligomerization of UG (K(assoc) approximately 230 M(-)(1),
      CDCl(3)). DeUG was prepared as a more robust analogue of UG lacking the Hoogsteen
      nitrogen atom. Remarkably, the deaza analogue, DeUG, forms a much more stable
      complex with DAN (>10-fold higher K(assoc) for DeUG.DAN vs UG.DAN) but also
      dimerizes more strongly (K(dim) = 880 +/- 40 M(-)(1), CDCl(3)) by adopting a
      conformation preorganized for both binding and dimerization.

PMID- 16597119
TI  - Supramolecular triplet photosensitizer. Effects of the cation binding mode on E-Z
      isomerization of 1,2-dichloroethylene.
AB  - [reaction: see text] Effects of metal cation recognition on photosensitized E-Z
      isomerization of 1,2-dichloroethylene have been investigated with two types of
      m,p- and o,o'-podand (oligo-oxyethylene unit) benzophenones 2 and 3. With
      increasing cation size, the %Z ratio at the photostationary state was changed
      from 67 to 91% for 2 but remained almost unchanged (86-88%) for 3. These results
      were interpreted in terms of the variation of excited triplet energy, E(T),
      associated with the cation complexation of these photosensitizers 2 and 3.

PMID- 16597118
TI  - Synthesis and anion binding properties of N,N'-bispyrrol-2-yl-2,5-diamidopyrrole.
AB  - [structure: see text] A bispyrrol-2-yl-2,5-diamidopyrrole has been synthesized
      and shown to have a significantly higher affinity for oxo-anions than previous
      generation 2,5-diamidopyrroles.

PMID- 16597120
TI  - Fluorescent ratiometry of tetrahomodioxacalix[4]arene pyrenylamides upon cation
      complexation.
AB  - [structure: see text] C-1,2-alternate tetrahomodioxacalix[4]arene pyreneamides
      were synthesized. Pb(2+) coordination gave a quenched monomer and excimer
      fluorescence emission, while upon Ca(2+) ion binding, the receptor provides an
      enhanced excimer and declined monomer emission with ratiometric response. The
      excimer emission spectra changes are rationalized by frontier molecular orbitals
      that the effective Py-Py interaction induces emission intensity increases upon
      Ca(2+) ion complexation, whereas there is no such interaction observed upon
      Pb(2+) binding.

PMID- 16597122
TI  - De novo asymmetric synthesis of D- and L-swainsonine.
AB  - [reaction: see text] The enantioselective syntheses of both enantiomers of the
      indolizidine natural product swainsonine have been achieved in 13 steps from
      furan. The indolizidine ring system is installed by a one-pot hydrogenolysis of
      both an azide and an O-Bn group along with an intramolecular reductive amination
      reaction. The asymmetry of swainsonine was introduced by Noyori reduction of an
      acylfuran. This route relies upon an Achmatowicz rearrangement, a
      diastereoselective palladium-catalyzed glycosylation, Luche reduction, and a
      dihydroxylation reaction.

PMID- 16597121
TI  - Synthetic studies toward mannopeptimycin-E: synthesis of the O-linked tyrosine
      1,4-alpha,alpha-manno,manno-pyranosyl pyranoside.
AB  - [structure: see text] The enantioselective synthesis of the C-4' acylated 1,4
      alpha,alpha-manno,manno-disaccharide fragment of mannopeptimycin-E has been
      achieved in seven steps from d-tyrosine. The route relies upon diastereoselective
      palladium-catalyzed glycosylation, diastereoselective reduction, and
      diastereoselective bis-dihydroxylation. The efficiency of the synthesis is
      demonstrated by the high overall yield (37%) and the preparation of various
      analogues.

PMID- 16597123
TI  - Enantioselective total synthesis of litseaverticillols A and B.
AB  - [reaction: see text] The first enantioselective total synthesis of the (1R,5S)
      stereoisomer of litseaverticillols A and B, anti-HIV monocyclic sesquiterpenoids
      isolated from a perennial shrub found in Vietnam, was accomplished in six steps
      from homogeranic acid by employing the Evans asymmetric aldol reaction and a
      microwave-promoted cyclization of a stannylated thiol ester intermediate as the C
      C bond-forming steps.

PMID- 16597124
TI  - Enantioselective synthesis and absolute configuration assignment of gabosine O.
      Synthesis of (+)- and (-)-gabosine N and (+)- and (-)-epigabosines N and O.
AB  - [reaction: see text] A rational approach to the synthesis of gabosines and other
      related carba-sugars starting from a masked p-benzoquinone has been designed. The
      enantioselective acetylation of the hydroxyketal 2 provides a practical entry to
      either enantiomer of the target products. The strategy has been applied to the
      synthesis of (+)- and (-)-gabosines N and O and (+)- and (-)-epigabosines N and
      O. The absolute configuration of natural gabosine O has been established.

PMID- 16597125
TI  - Asymmetric Friedel-Crafts addition of indoles to N-sulfonyl aldimines: a simple
      approach to optically active 3-indolyl-methanamine derivatives.
AB  - [reaction: see text] The enantioselective copper(II)-catalyzed Friedel-Crafts
      addition of indoles to N-sulfonyl aldimines was developed using chiral
      bisoxazoline as ligands, and high enantioselectivities (up to 96% ee) were
      achieved.

PMID- 16597127
TI  - Stereoselective synthesis of protected 1,2-diols and 1,2,3-triols by a tandem
      hydroboration-coupling sequence.
AB  - [reaction: see text] A new approach to complex chiral diols and polyols is
      described utilizing a tandem hydroboration/Suzuki cross-coupling reaction. This
      method utilizes the versatility of a glycolate-derived chiral template.

PMID- 16597126
TI  - Thionation using fluorous Lawesson's reagent.
AB  - [reaction: see text] Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides,
      N,N'-acylhydrazines, and acyl-protected uridines with the use of a fluorous
      analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3
      thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation
      of the final products in high yields is achieved in most cases by a simple
      filtration (fluorous solid-phase extraction).

PMID- 16597128
TI  - The silylalkyne-Prins cyclization: stereoselective synthesis of tetra- and
      pentasubstituted halodihydropyrans.
AB  - [reaction: see text] A new type of Prins cyclization using silylated secondary
      homopropargylic alcohols and aldehydes yielding tetra- and pentasubstituted
      dihydropyrans is described. The presence of the trimethylsilyl group in the
      triple bond favors the Prins cyclization and minimizes the 2-oxonia-[3,3]
      sigmatropic rearrangement as a competitive alternative pathway. Ab initio
      theoretical calculations of the species involved in the rearrangements support
      the proposed mechanism. The process is highly stereoselective, affording cis
      dihydropyran as the only isomer.

PMID- 16597129
TI  - Ultrafast study of the photochemistry of 2-azidonitrobenzene.
AB  - [reaction: see text] Ultrafast time-resolved studies of the photochemistry of 2
      azidonitrobenzene demonstrate that the lifetimes of excited singlet 2
      azidonitrobenzene and 2-nitrophenylnitrene are 500 fs and 8.3 ps, respectively,
      in solution at ambient temperature. The singlet nitrene is a discrete
      intermediate but is too short lived to undergo bimolecular reactions.

PMID- 16597130
TI  - A chromogenic macrocycle exhibiting cation-selective and anion-controlled color
      change: an approach to understanding structure-color relationships.
AB  - [reaction: see text] A N-azo-coupled macrocycle (1) with a NO(2)S(2) donor set
      was synthesized as a chromoionophore and shown to exhibit Hg(2+) selectivity;
      anion control of the color of the Hg(2+) complex was observed. As a first
      approach, the nature of the color generation process was probed by determining
      the crystal structures of the two different colored species obtained with
      perchlorate and iodide anions. The results can be explained in terms of a "Push-n
      Pull Process", which serves to illustrate how the coordinating ability of the
      anion controls the color change through formation of endo- or exo-metal
      complexes. The use of "simple" salts to induce color-switching of the above
      complex species was also reported.

PMID- 16597131
TI  - Discovery of fluorescent cyanopyridine and deazalumazine dyes using small
      molecule macroarrays.
AB  - [structure: see text] Small molecule macroarrays of cyanopyridines and
      deazalumazines were generated in high purities via spatially addressed synthesis
      on planar cellulose supports. Examination of the spectral properties of the
      heterocycles both on and off of the planar support revealed a set of promising
      new fluorescent dyes that exhibit high quantum yields, low pH dependence, and
      high sensitivity to solvent polarity.

PMID- 16597132
TI  - A colorimetric boronic acid based sensing ensemble for carboxy and phospho
      sugars.
AB  - [structure: see text] A cadmium-centered tris-boronic acid receptor was
      synthesized, and its binding properties toward various anionic sugars were
      determined. This receptor shows high affinity for different anionic sugars,
      especially gluconic acid, which has an association constant near approximately
      10(7) M(-)(1) at neutral pH. Further, using an indicator displacement assay, a
      color change of pyrocatechol violet was observed upon addition of anionic sugars.
      This colorimetric test was used as a facile screening technique to qualitatively
      analyze guest affinities.

PMID- 16597133
TI  - Efficient chemoenzymatic synthesis of pelitrexol via enzymic differentiation of a
      remote stereocenter.
AB  - [structure: see text] An efficient chemoenzymatic process is described for the
      synthesis of pelitrexol, a novel GARFT inhibitor. The remoteness of this
      molecule's stereocenter in the tetrahydropterin moiety from the terminal carbonyl
      group provided a significant challenge in synthesis. The introduction of an
      oxalamic ester adjacent to the stereocenter dramatically enhanced an enzyme's
      enantioselectivity for hydrolysis at the terminal ester, producing the desired S
      acid with high optical purity and yield. The recycling of the "wrong" enantiomer
      is achieved via a dehydrogenation/hydrogenation strategy.

PMID- 16597134
TI  - Efficient Heck arylations of cyclic and acyclic acrylate derivatives using
      arenediazonium tetrafluoroborates. A new synthesis of the antidepressant drug (+/
      )-paroxetine.
AB  - [reaction: see text] The Heck arylation of acyclic- and cyclic-substituted
      acrylates using several arenediazonium tetrafluoroborates was investigated.
      Arylations were carried out under aerobic, ligand-free conditions to provide the
      corresponding substituted acrylates in moderate to high isolated yields. Heck
      arylations were usually completed in less than 2 h in refluxing methanol. The aza
      endocyclic acrylate derivative 11a was converted into the antidepressant drug (+/
      )-paroxetine in a concise new route in good overall yield.

PMID- 16597135
TI  - Formal synthesis of aspidosperma alkaloids via the intramolecular [3 + 2]
      cycloaddition of 2-azapentdienyllithiums.
AB  - [reaction: see text] A formal synthesis of the Aspidosperma alkaloids
      aspidospermidine, aspidospermine, and quebrachamine is reported through an
      efficient preparation of Stork's penultimate intermediate. The key step of the
      sequence involved an intramolecular [3 + 2] cycloaddition of the 2
      azapentadienyllithium 21 formed in situ from the corresponding imine 1, which
      after N-alkylation of the resulting cycloadduct provided 2 in excellent yield.
      The synthesis represents a new disconnection of the classical tricyclic ketone
      used for appendage of the requisite indole.

PMID- 16597136
TI  - Indole diterpenoid synthetic studies. The total synthesis of (+)-nodulisporic
      acid F.
AB  - [structure: see text] A stereocontrolled total synthesis of (+)-nodulisporic acid
      F, the simplest member of a family of novel ectoparasiticidal agents, has been
      achieved. Highlights of the effective modular synthetic strategy include anionic
      union of a tricyclic lactone with o-toluidine via our 2-substituted indole
      synthetic protocol, an optimized C-ring construction protocol, and a late-stage
      installation of the alpha,beta-unsaturated carboxylic acid side chain via the B
      alkyl Suzuki-Miyaura cross-coupling tactic.

PMID- 16597138
TI  - Temporary phosphate tethers: a metathesis strategy to differentiated polyol
      subunits.
AB  - [reaction: see text] Studies probing reactivity and selectivity of cross
      metathesis (CM) with an exocyclic olefin in a P-chiral bicyclo[4.3.1]phosphate
      triester are described. Studies have revealed a Type III CM reactivity pattern
      for the exocyclic olefin within this phosphate triester. This versatile method
      allows for simple, selective manipulation of a P-chiral building block en route
      to advanced polyol subunits.

PMID- 16597137
TI  - Indole diterpenoid synthetic studies. Construction of the heptacyclic core of (-)
      nodulisporic acid D.
AB  - [structure: see text] Construction of the heptacyclic core of (-)-nodulisporic
      acid D, a representative member of a recently discovered class of architecturally
      complex, ectoparasiticidal indole alkaloids, has been achieved. The modular
      synthetic strategy comprises an expedient, stereocontrolled synthesis of a
      tricyclic western hemisphere, in conjunction with union of an eastern hemisphere,
      exploiting the 2-substituted indole synthetic protocol introduced and developed
      in our laboratory.

PMID- 16597139
TI  - High atom-economical one-pot synthesis of secondary phosphines and their borane
      complexes using recycling phosphorus donor reagent.
AB  - [reaction: see text] A general new method for the one-pot preparation of
      secondary phosphines 11 and in situ generation of their borane complexes 12 is
      described. This method consists of the sequential addition, at room temperature,
      of equivalent amounts of R(1)MgBr and R(2)MgBr to 1 equiv of the phosphorus atom
      donor reagent 1. Final treatment with water gives secondary phosphines R(1)R(2)PH
      (or the corresponding phosphine-borane complexes if treated with BH(3).THF) and
      the end product 6, which can be recycled.

PMID- 16597141
TI  - Cyclocarbopalladation of alkynes: a stereoselective method for preparing
      dibenzoxapine containing tetrasubstituted exocyclic alkenes.
AB  - [reaction: see text] A palladium-catalyzed cascade carbometalation-cross coupling
      of alkyne route was developed for the preparation of tetrasubstituted exocyclic
      alkenes with high stereo- and regiocontrol. The effectiveness of this novel
      methodology was demonstrated by the synthesis of a number of dibenzoxapines in
      sufficient quantities to support their further development.

PMID- 16597140
TI  - Azabicycloalkenes as synthetic intermediates: application to the preparation of
      diazabicycloalkane scaffolds.
AB  - [reaction: see text] A general method to synthesize bicyclic dipeptide mimetics
      is reported. Key intermediates are azabicycloalkenes 9 and 17, which are prepared
      via Diels-Alder reactions and subsequent mild deprotection. These unsaturated
      bicyclic heterocycles are versatile intermediates for different dipeptide
      mimetics of the aza- and diazabicycloalkane type, which is demonstrated by the
      synthesis of diazabicycloalkanes 11 and 19 in only 3-6 steps and good overall
      yield.

PMID- 16597142
TI  - Reusable polymer-supported catalyst for the [3+2] Huisgen cycloaddition in
      automation protocols.
AB  - [reaction: see text] A polymer-supported catalyst for Huisgen's [3+2]
      cycloaddition reaction between azides and alkynes was prepared from copper(I)
      iodide and Amberlyst A-21. This catalyst was then used in an automated synthesis
      of 1,4-disubstituted 1,2,3-triazoles giving access to these products in good
      yields. The catalyst has shown good activity, stability, and recycling
      capabilities.

PMID- 16597143
TI  - Stereoselective nucleophilic monofluoromethylation of N-(tert
      butanesulfinyl)imines with fluoromethyl phenyl sulfone.
AB  - [reaction: see text] Highly stereoselective nucleophilic monofluoromethylation of
      (R)-(tert-butanesulfinyl)imines with fluoromethyl phenyl sulfone was achieved to
      afford alpha-monofluoromethylamines with a nonchelation-controlled
      stereoselectivity mode. By using the same chemistry, (R)-(tert
      butanesulfinyl)imines bearing a terminal tosylate (OTs) group can be converted to
      alpha-monofluoromethylated cyclic secondary amines with high stereoselectivity.

PMID- 16597144
TI  - Tuning the electrical and optical properties of dinuclear ruthenium complexes for
      near infrared optical sensing.
AB  - [reaction: see text] Redox-active dinuclear ruthenium complexes with various 1,2
      dicarbonylhydrazido (DCH) ligands are designed and prepared to have intense
      absorption in the near-infrared region for potential optical sensing in aqueous
      media, as demonstrated for sensing hydrogen peroxide in this study.

PMID- 16597145
TI  - Facile synthesis of enantiopure chiral molecular rectangles exhibiting induced
      circular dichroism.
AB  - [structure: see text] The facile syntheses of enantiopure molecular rectangles
      using 1,8-bis(trans-Pt(PEt(3))(2)(NO(3)))anthracene and optically pure d- or l
      tartrate are reported in high yields. These self-assembled macrocycles are unique
      examples where the phenomenon of induced chiral dichroism (ICD) has been observed
      in chiral metallosupramolecular assemblies.

PMID- 16597146
TI  - Solid-phase synthesis of succinylhydroxamate peptides: functionalized matrix
      metalloproteinase inhibitors.
AB  - [reaction: see text] A novel solid-phase synthesis strategy toward
      succinylhydroxamate peptides, using an appropriately protected hydroxamate
      building block, is described. Rapid and efficient access is gained to amine
      functionalized peptides, which can be decorated with, for instance, a fluorescent
      label. In addition, we demonstrate an on-resin synthesis of a biotinylated
      photoactivatable hydroxamate peptide, which can be used as an activity-based
      probe for matrix metalloproteinases and ADAMs.

PMID- 16597147
TI  - A stereoselective synthetic route to 1,6-Dioxaspiro[4.4]non-3-en-2-ones from
      cyclopropyl alkyl ketones and alpha-ketoesters.
AB  - [reaction: see text] The SnCl(4)-mediated reactions of cyclopropyl alkyl ketones
      with alpha-ketoesters afford a novel method for the synthesis of 1,6
      dioxaspiro[4.4]non-3-en-2-ones with high stereoselectivities in moderate to good
      yields. This process is a sequential reaction involving a nucleophilic ring
      opening reaction of the cyclopropane by H(2)O, an aldol-type reaction, and a
      cyclic transesterification mediated by Lewis acid.

PMID- 16597148
TI  - En route to a motorized nanocar.
AB  - [structure: see text] With the eventual goal of demonstrating a motorized
      nanocar, the key structure has been synthesized which bears a light-activated
      unidirectional molecular motor and an oligo(phenylene ethynylene) chassis and
      axle system with four carboranes to serve as the wheels. Kinetics studies in
      solution show that the motor indeed rotates upon irradiation with 365 nm light,
      and the fullerene-free carborane wheel system is an essential design feature for
      motor operation.

PMID- 16597149
TI  - Novel bicyclization reaction leading to a fused beta-lactone.
AB  - [reaction: see text] The reaction of acrylyl chloride with the above amino ketone
      in the presence of pyridine produces bicyclic beta-lactones rather than the
      corresponding acrylamide, which can be the major product under other conditions.

PMID- 16597150
TI  - Catalytic asymmetric protonation of lithium enolates using amino acid derivatives
      as chiral proton sources.
AB  - [reaction: see text] Asymmetric protonation of lithium enolates was examined
      using commercially available amino acid derivatives as chiral proton sources.
      Among the amino acid derivatives tested, Nbeta-l-aspartyl-l-phenylalanine methyl
      ester was found to cause significant asymmetric induction in the protonation of
      lithium enolates. The enantiomeric excess (up to 88% ee) of the products obtained
      in the presence of a catalytic amount of the chiral proton source was higher than
      those obtained in the stoichiometric reaction.

PMID- 16597151
TI  - A concise and selective synthesis of novel 5-aryloxyimidazole NNRTIs.
AB  - [reaction: see text] A concise and efficient route to the construction of a 5
      aryloxyimidazole has been developed. The key step was the selective O-arylation
      of a 2,4-dimethoxybenzyl-protected imidazolone. The final compound is a potent
      inhibitor of HIV reverse transcriptase.

PMID- 16597152
TI  - Identification of a potent botulinum neurotoxin a protease inhibitor using in
      situ lead identification chemistry.
AB  - [reaction: see text] Botulinum neurotoxins (BoNTs), etiological agents of the
      deadly food poisoning disease botulism, are the most toxic proteins currently
      known. By using in situ lead identification chemistry, we have uncovered the
      first class of inhibitors that displays nanomolar potency. From a 15 microM lead
      compound, structure-activity relationship studies were performed granting the
      most potent BoNT/A inhibitor reported to date that displays an inhibition
      constant of 300 nM.

PMID- 16597153
TI  - Arboflorine, an unusual pentacyclic monoterpenoid indole alkaloid incorporating a
      third nitrogen atom.
AB  - [structure: see text] A new indole alkaloid, arboflorine, possessing a novel
      pentacyclic carbon skeleton and incorporating a third nitrogen atom was obtained
      from the Malayan Kopsia arborea. The structure was established by spectroscopic
      analysis, and a possible biogenetic pathway from a preakuammicine-type precursor
      is presented.

PMID- 16597154
TI  - Enantioconvergent hydrolysis of styrene epoxides by newly discovered epoxide
      hydrolases in mung bean.
AB  - [reaction: see text] Two novel epoxide hydrolases were discovered in mung bean
      (Phaseolus radiatus L.) for the first time, either of which can catalyze
      enantioconvergent hydrolysis of styrene epoxides. Their regioselectivity
      coefficients are more than 90% for the p-nitrostyrene oxide. Furthermore, the
      crude mung bean powder was also shown to be a cheap and practical biocatalyst,
      allowing a one-step asymmetric synthesis of chiral (R)-diols from racemic
      epoxides, in up to >99% ee and 68.7% overall yield (after recrystallization).

PMID- 16597155
TI  - Ru-catalyzed ring-opening and substitution reactions of heteroaromatic compounds
      using propargylic carboxylates as precursors of vinylcarbenoids.
AB  - [reaction: see text] The reaction of heteroaromatic compounds with propargylic
      carboxylates in the presence of a catalytic amount of [RuCl(2)(CO)(3)](2) or
      PtCl(2) gives trienes in good yields. The key intermediate is an electrophilic (1
      acetoxylvinyl)carbene complex generated from the activated propargylic acetates
      with transition metals.

PMID- 16597156
TI  - Enantioselective synthesis of a PKC inhibitor via catalytic C-H bond activation.
AB  - [reaction: see text] The syntheses of two biologically active molecules
      possessing dihydropyrroloindole cores (1 and 2) were completed using rhodium
      catalyzed imine-directed C-H bond functionalization, with the second of these
      molecules containing a stereocenter that can be set with 90% ee during
      cyclization using chiral nonracemic phosphoramidite ligands. Catalytic
      decarbonylation and direct indole/maleimide coupling provide efficient access to
      2.

PMID- 16597159
TI  - Corticosteroid-sparing strategies in renal transplantation: are we still
      balancing rejection risk with improved tolerability?
AB  - Chronic allograft nephropathy and death with a functioning graft (mainly due to
      cardiovascular causes) are the most common causes of graft loss after the first
      year of renal transplantation. Immunosuppressants, and corticosteroids among
      them, contribute to an increase in cardiovascular risk because of their
      significant adverse effects, including hypertension, hyperlipidaemia and
      hyperglycaemia. Thus, corticosteroid discontinuation or avoidance has become a
      priority among the transplant community in order to enhance long-term graft and
      patient survival. Nevertheless, corticosteroid-sparing strategies may increase
      the risk of acute and chronic rejection and, thus, worsen the prognosis of
      transplant recipients. Initial attempts during the azathioprine epoch did not
      provide satisfactory results, as they were associated with high acute rejection
      rates, emphasising the risk of under-immunosuppression. The advent of new
      immunosuppressants, such as mycophenolate mofetil, mTOR inhibitors and anti
      interleukin-2 receptor antibodies, have renewed the interest in corticosteroid
      sparing protocols, and the results of new trials suggest that these
      corticosteroid-sparing strategies, even at an early stage after transplantation,
      are safe enough in view of the stable renal function and low rates of acute
      rejection reported. However, immunological risk factors, such as African American
      ethnicity, the presence of panel-reactive anti-HLA antibodies (even at low
      rates), and a history of previous acute rejection episodes should be taken into
      account and corticosteroid withdrawal strategies should be undertaken with
      caution. Long-term follow-up studies must be performed to confirm the encouraging
      short-term data.

PMID- 16597161
TI  - Post-transplant lymphoproliferative disease: association with induction therapy?
AB  - In the last 2 decades, several polyclonal and monoclonal antibodies have been
      developed for induction therapy in the early post solid-organ transplantation
      period. The use of these antibodies has been associated, for the most part, with
      a decrease in early acute rejection rates. However, there has been a simultaneous
      rise in infectious complications, particularly in the incidence of post
      transplant lymphoproliferative disease (PTLD). Determinations of adjusted odds
      ratios or relative risk have yielded conflicting information regarding whether
      these antibody agents increase the risk for PTLD. In order to interpret the
      results of the different studies, the reader requires a detailed knowledge of the
      types of analyses performed and the characteristics of the populations studied.
      This article analyses the available data on PTLD risk after the use of induction
      antibody agents. While some studies suggest an increased risk of PTLD after
      induction antibody use, other studies do not; the available data are not
      conclusive either way at this time.

PMID- 16597160
TI  - Dexamethasone in adults with community-acquired bacterial meningitis.
AB  - Bacterial meningitis in adults is a severe disease with high fatality and
      morbidity rates. Experimental studies have shown that the inflammatory response
      in the subarachnoid space is associated with an unfavourable outcome. In these
      experiments, corticosteroids, and in particular dexamethasone, were able to
      reduce the inflammatory cascades in the subarachnoid space. The use of
      corticosteroids as adjunctive therapy in adults with bacterial meningitis has
      been evaluated in six studies, performed over a time period of 40 years. Most
      studies on adjunctive dexamethasone therapy in adults with bacterial meningitis
      were limited by methodological flaws. In 2002, a study with sufficient
      statistical power to show significant differences was published. This European
      Dexamethasone Study showed that adjunctive dexamethasone therapy reduced the rate
      of unfavourable outcomes in adults with bacterial meningitis from 25% to 15%. In
      this study, adjunctive treatment with dexamethasone was given before or with the
      first dose of antibacterials, without serious adverse effects. A quantitative
      review showed a consistent beneficial effect of dexamethasone on mortality and a
      borderline statistical beneficial effect on neurological sequelae. On the basis
      of the available evidence, adjunctive dexamethasone therapy should be initiated
      before or with the first dose of antibacterials and continued for 4 days in all
      adults with suspected or proven bacterial meningitis, regardless of bacterial
      aetiology. In patients with both meningitis and septic shock, dexamethasone
      therapy cannot be unequivocally recommended, but the use of lower doses seems
      reasonable at present. Since prompt use of dexamethasone and appropriate
      antibacterials improves the prognosis of adults with bacterial meningitis,
      hospitals will require protocols to include dexamethasone with the initial
      antibacterial therapy.

PMID- 16597162
TI  - Therapeutic potential of ghrelin in the treatment of heart failure.
AB  - Ghrelin is a novel growth hormone (GH)-releasing peptide, isolated from the
      stomach, which has been identified as an endogenous ligand for the GH
      secretagogues receptor. The discovery of ghrelin indicates that the release of GH
      from the pituitary might be regulated, not only by hypothalamic GH-releasing
      hormone, but also by ghrelin derived from the stomach. Considering the
      haemodynamic and anabolic effects of GH, ghrelin may have beneficial effects on
      cardiac function and energy metabolism in heart failure through GH-dependent
      mechanisms. On the other hand, ghrelin has some GH-independent actions: ghrelin
      stimulates food intake and induces adiposity. Interestingly, ghrelin acts
      directly on the CNS to decrease sympathetic nerve activity. It also inhibits
      apoptosis of cardiomyocytes and endothelial cells. An experimental study has
      shown that repeated administration of ghrelin improves cardiac structure and
      function, and attenuates the development of cardiac cachexia in chronic heart
      failure (CHF). These results suggest that ghrelin has cardiovascular effects and
      regulates energy metabolism through GH-dependent and -independent mechanisms.
      Thus, administration of ghrelin may be a new therapeutic strategy for the
      treatment of severe CHF.

PMID- 16597163
TI  - Trastuzumab: a review of its use in the management of HER2-positive metastatic
      and early-stage breast cancer.
AB  - Trastuzumab (Herceptin) is a humanised monoclonal antibody used in the treatment
      of breast cancer that overexpresses human epidermal growth factor receptor 2
      (HER2), which is associated with clinically aggressive disease and a poor
      prognosis. The addition of intravenous trastuzumab to first-line chemotherapy
      improved the time to disease progression, objective response rate, duration of
      response, and overall survival in randomised, multicentre trials in women with
      HER2-positive metastatic breast cancer. As such, trastuzumab has become the
      standard of care in this setting, despite its high acquisition cost and potential
      for cardiac events, and is licensed for use in combination with paclitaxel
      (Europe and the US) or docetaxel (Europe). In addition, trastuzumab monotherapy
      is approved for use in patients with HER2-positive metastatic breast cancer who
      have previously received chemotherapy for their metastatic disease. Recent data
      from large phase III trials with trastuzumab in the adjuvant setting revealed
      significant improvements in disease-free and overall survival. Thus, trastuzumab
      is also rapidly becoming a standard component of adjuvant therapy for patients
      with HER2-positive early-stage breast cancer.

PMID- 16597164
TI  - Moxonidine: a review of its use in essential hypertension.
AB  - Moxonidine (Physiotens, Moxon, Cynt) is an orally administered imidazoline
      compound with selective agonist activity at imidazoline I1 receptors and only
      minor activity at alpha2-adrenoceptors. Moxonidine acts centrally to reduce
      peripheral sympathetic activity, thus decreasing peripheral vascular resistance.
      In patients with mild to moderate hypertension, moxonidine reduces blood pressure
      (BP) as effectively as most first-line antihypertensives when used as monotherapy
      and is also an effective adjunctive therapy in combination with other
      antihypertensive agents. It improves the metabolic profile in patients with
      hypertension and diabetes mellitus or impaired glucose tolerance, is well
      tolerated, has a low potential for drug interactions and may be administered once
      daily in most patients. Thus, moxonidine is a good option in the treatment of
      patients with mild to moderate hypertension, particularly as adjunctive therapy
      in patients with the metabolic syndrome.

PMID- 16597166
TI  - Rasburicase: a review of its use in the management of anticancer therapy-induced
      hyperuricaemia.
AB  - Intravenous rasburicase (Elitek, Fasturtec) is the first recombinant uricolytic
      agent. It is indicated for the management of anticancer therapy-induced
      hyperuricaemia in paediatric patients in the EU and US, and in adult patients in
      the EU. Rasburicase is effective and generally well tolerated in adult and
      paediatric patients with, or at risk of developing, anticancer therapy-induced
      hyperuricaemia. It is associated with potentially serious haematological adverse
      events and hypersensitivity reactions, which must be considered prior to and
      during administration; rasburicase is contraindicated in patients predisposed to
      haemolysis or methaemoglobinaemia and in patients with glucose-6-phosphate
      dehydrogenase deficiency. Unlike allopurinol, rasburicase acts on existing uric
      acid concentrations. Rasburicase treatment resulted in significantly less
      systemic exposure to uric acid and a quicker therapeutic response than
      allopurinol in paediatric patients; further studies are needed to determine the
      comparative efficacy and tolerability of rasburicase versus allopurinol in adult
      patients. Although further pharmacoeconomic data would be useful, rasburicase was
      most cost effective for the prevention of hyperuricaemia in children and for
      treatment of this condition in adults. Thus, rasburicase is a useful option for
      the prophylaxis or treatment of anticancer therapy-induced hyperuricaemia in both
      adult and paediatric patients.

PMID- 16597165
TI  - Modified-release nifedipine: a review of the use of modified-release formulations
      in the treatment of hypertension and angina pectoris.
AB  - Nifedipine is a dihydropyridine calcium channel antagonist with predominantly
      vasodilatory activity. Modified-release formulations of nifedipine are effective
      antihypertensive and antianginal therapies and are generally well tolerated.
      Among the available formulations, those that produce a gradual increase in plasma
      nifedipine concentration, which is then sustained over a 24-hour period, are
      preferred, as they cause a gradual onset of vasodilatation and avoid baroreflex
      sympathetic activation (for example, nifedipine gastrointestinal therapeutic
      system [GITS] and a Japanese controlled-release formulation). Modified-release
      nifedipine had beneficial effects on a number of markers of vascular function,
      and nifedipine GITS reduced the need for coronary procedures in patients with
      coronary artery disease. In patients with hypertension, nifedipine GITS and
      nifedipine retard had beneficial effects on the overall incidence of major
      cardiovascular events, as did nifedipine retard in patients with concurrent
      hypertension and coronary artery disease.

PMID- 16597167
TI  - Everolimus: a review of its use in renal and cardiac transplantation.
AB  - Everolimus (Certican) is an orally administered mammalian target of rapamycin
      inhibitor (proliferation signal inhibitor) derived from sirolimus (rapamycin),
      which is used as part of immunosuppressant therapy in kidney and heart
      transplantation. When evaluated as part of triple therapy with ciclosporin and
      corticosteroids, everolimus showed equivalent efficacy to mycophenolate mofetil
      after renal transplantation, and superiority to azathioprine in cardiac
      transplant recipients, in terms of reducing efficacy failure after
      transplantation. Everolimus potentiates ciclosporin-associated nephrotoxicity,
      and it is recommended that concentration-controlled everolimus is used with
      reduced-dosage ciclosporin in order to limit renal toxicity while retaining
      immunosuppressive efficacy. Ongoing trials with everolimus, such as the
      evaluation of ciclosporin-withdrawal strategies, should help clarify its optimal
      usage. The use of everolimus may be associated with reduced rates of
      cytomegalovirus (CMV) infection and of cardiac allograft vasculopathy. Available
      data suggest that everolimus may be cost-neutral for healthcare providers.

PMID- 16597168
TI  - Hexyl aminolevulinate: in the detection of bladder cancer.
AB  - Hexyl aminolevulinate, the hexyl ester of 5-aminolevulinic acid, is a
      photosensitising agent designed to enhance the detection of bladder cancer
      tumours, in particular highly malignant carcinoma in situ (CIS). After cellular
      uptake, hexyl aminolevulinate and/or hydrolysed 5-aminolevulinic acid enter the
      haem biosynthetic pathway and induce accumulation of the photoactive compound
      protoporphyrin IX (PpIX) in malignant as opposed to nonmalignant cells. PpIX
      emits red fluorescence when illuminated under blue light. Blue-light fluorescence
      cystoscopy with hexyl aminolevulinate (hexyl aminolevulinate cystoscopy) was more
      effective than standard (white-light) cystoscopy for detecting non-muscle
      invasive ('superficial') disease in two European, multicentre, phase III trials,
      which evaluated hexyl aminolevulinate cystoscopy as an adjunct to standard
      cystoscopy in patients with known or suspected bladder cancer. In one trial,
      hexyl aminolevulinate cystoscopy detected 96% of the patients with CIS; it
      identified 28% more patients with CIS than standard cystoscopy. In the other
      trial, 17% of patients were selected to receive more complete treatment following
      hexyl aminolevulinate cystoscopy than standard cystoscopy, because of the
      improved tumour detection rate. Hexyl aminolevulinate cystoscopy is well
      tolerated as an adjunct to standard cystoscopy; adverse events were those
      typically associated with standard cystoscopy/biopsy (e.g. postoperative pain).

PMID- 16597172
TI  - Bigger and better: how Pfizer redefined erectile dysfunction.

PMID- 16597173
TI  - Cholinesterase inhibitors: drugs looking for a disease?

PMID- 16597174
TI  - Combating disease mongering: daunting but nonetheless essential.

PMID- 16597175
TI  - Giving legs to restless legs: a case study of how the media helps make people
      sick.

PMID- 16597176
TI  - Female sexual dysfunction: a case study of disease mongering and activist
      resistance.

PMID- 16597177
TI  - Medicine goes to school: teachers as sickness brokers for ADHD.

PMID- 16597178
TI  - The latest mania: selling bipolar disorder.

PMID- 16597179
TI  - Pharmaceutical marketing and the invention of the medical consumer.

PMID- 16597180
TI  - The fight against disease mongering: generating knowledge for action.

PMID- 16597181
TI  - Disease mongering in drug promotion: do governments have a regulatory role?

PMID- 16597182
TI  - Awareness and attitudes about disease mongering among medical and pharmaceutical
      students.

PMID- 16597183
TI  - Meta-analysis of comparative studies of depression in mothers of children with
      and without developmental disabilities.
AB  - Meta-analysis was used to synthesize findings from comparative studies of
      depression in mothers of children with and without developmental disabilities.
      Effect sizes were determined for 18 studies conducted between 1984 and 2003. A
      weighted effect size of .39 indicated an elevated level of depression in mothers
      of children with developmental disabilities. Planned comparisons found that age
      of child and disability category moderated effect sizes. Results show that
      mothers of children with developmental disabilities are at elevated risk of
      depression compared to mothers of typically developing children. Depression in
      mothers of children with developmental disabilities is a condition that is
      presently not being addressed on a wide scale, although promising interventions
      are available.

PMID- 16597184
TI  - Collaboration in referential communication: comparison of youth with down
      syndrome or fragile X syndrome.
AB  - Referential communication was examined in youth with Down syndrome or fragile X
      syndrome in comparison to each other and to MA-matched typically developing
      children. A non-face-to-face task was used in which the participant repeatedly
      described novel shapes to listeners. Several dimensions of referential
      communication were especially challenging for the syndrome groups (i.e., they
      displayed below-MA performance), although there were differences in the
      dimensions that each syndrome group found to be most challenging. Independently
      assessed expressive language ability contributed to variations in referential
      performance, especially for participants with Down syndrome.

PMID- 16597185
TI  - Effects of social context on social interaction and self-injurious behavior in
      Cornelia de Lange syndrome.
AB  - Cornelia de Lange syndrome is reported to be associated with self-injurious
      behavior (SIB) and social avoidance. We used analog methodology to examine the
      effect of manipulating adult social contact on social communicative behaviors and
      SIB in 16 children with this syndrome. For 9 participants engagement behavior was
      related to levels of adult attention, and SIB showed significant variability
      across conditions for 3 participants. These findings indicate that SIB can be
      affected by environmental factors, even though it is thought to be part of the
      behavioral phenotype of Cornelia de Lange syndrome and suggest that individuals
      with this syndrome show socially motivated attention-soliciting behaviors. The
      implications for gene-environment interactions are discussed.

PMID- 16597186
TI  - Mortality in Prader-Willi syndrome.
AB  - Persons with Prader-Willi syndrome have been known to have a high mortality rate.
      However, intellectual disability, which usually accompanies Prader-Willi
      syndrome, is also associated with a higher mortality rate than in the general
      population. In this study, the death rates in a longitudinal cohort of people
      with Prader-Willi syndrome are compared with those for an epidemiologically
      derived control sample of people with intellectual disability from other causes.
      We found that those with Prader-Willi syndrome had a higher mortality rate than
      did controls. After the protective effect of mild intellectual disability or
      average intellectual function was accounted for, the hazard ratio for Prader
      Willi syndrome versus controls was 6.07. Obesity and its complications were
      factors contributing to the mortality identified in this study.

PMID- 16597187
TI  - Validity of the autism diagnostic interview-revised.
AB  - The factor structure, internal consistency, and convergent validity of the Autism
      Diagnostic Interview-Revised (ADI-R) algorithm items were examined in a sample of
      226 youngsters with pervasive developmental disabilities. Exploratory factor
      analyses indicated a three-factor solution closely resembling the original
      algorithm and explaining 38% of the variance, with one significant discrepancy:
      Unlike the algorithm, all nonverbal communication items were associated with the
      Social factor. Internal consistencies of domain scores ranged from .54 to .84.
      Correlations between ADI-R domain and total scores and instruments assessing
      adaptive behavior, psychopathology, and autism were examined. They indicated some
      similarities between constructs, but also that the ADI-R measures autism in a
      unique fashion.

PMID- 16597188
TI  - Interference and inhibition in tasks of selective attention by persons with and
      without mental retardation.
AB  - Persons with mental retardation often exhibit greater interference in visual
      selective attention tasks than do persons matched with them on CA. My goal here
      was to evaluate whether differences in distractor interference between persons
      with and without mental retardation may be related to differences in negative
      priming. Fifteen participants with mental retardation, 15 without mental
      retardation matched on CA, and 15 without mental retardation matched on MA
      participated in three selective attention tasks, which were chosen to elicit
      small, medium, and large group differences in interference, respectively. The
      failure to engage in inhibitory processes by the participants with mental
      retardation in these tasks of selective attention was related to increased
      distractor interference.

PMID- 16597190
TI  - Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and
      treatment.
AB  - The phasing out of leaded gasoline for transportation vehicles between 1973 and
      1995 and the removal of lead from paint by federal mandate by 1978 have resulted
      in substantial lowering of mean blood lead levels in all segments of the U.S.
      population. However, because lead is a persistent metal, it is still present in
      the environment - in water, brass plumbing fixtures, soil, dust, and imported
      products manufactured with lead. Diagnosis of lead toxicity has traditionally
      been based on significantly elevated blood lead levels. However, data now
      implicates low-level exposures and blood lead levels previously considered normal
      as causative factors in cognitive dysfunction, neurobehavioral disorders,
      neurological damage, hypertension, and renal impairment. Chelation is the
      conventional recommendation in the case of blood levels associated with acute
      toxicity and encephalopathic damage. Issues surrounding the assessment of body
      lead burden and the consequences of low-level environmental exposure are critical
      in the treatment of chronic disease related to lead toxicity.

PMID- 16597191
TI  - The effects of sustained-release-L-arginine formulation on blood pressure and
      vascular compliance in 29 healthy individuals.
AB  - Vascular endothelial function is crucial to cardiovascular function and thus to
      blood perfusion to the heart and throughout the body. A number of substances are
      produced and secreted by vascular endothelial cells, the most important of which
      is nitric oxide, a potent regulator of vascular function. Nitric oxide diffuses
      from endothelial cells into underlying smooth muscle, causing relaxation, which
      results in vasodilation. When this process is inhibited or inadequate the
      arteries cannot dilate as necessary, resulting in hypertonicity and reduced blood
      flow. Such endothelial dysfunction also causes increased platelet and monocyte
      adhesiveness and smooth muscle proliferation, processes thought to be at the
      genesis of atherosclerotic plaque formation. Since L-arginine is the body's only
      substrate for nitric oxide synthesis, adequate L-arginine must be present for
      proper nitric oxide production. In this open label trial, a group of 29
      asymptomatic individuals were given L-arginine (1,050 mg, as Perfusia-SR, a
      sustained-release preparation) twice daily (total 2.1 g daily) for one week.
      Systolic blood pressure was reduced in 62 percent of participants compared to
      baseline, with a non-significant mean decrease in all patients of 4 mm Hg.
      Diastolic blood pressure was reduced in 69 percent of participants, with a mean
      reduction of 3.7 mm Hg (p = 0.005). In the 10 individuals who were borderline or
      hypertensive (systolic > 130 or diastolic > 85), there was a mean systolic
      reduction of 11 mm Hg (p = 0.05), while normotensives (n = 19) had a mean
      systolic decrease of only 0.22 mm Hg. Diastolic blood pressure was decreased a
      non-significant 4.9 mm Hg in borderline or hypertensives and 4.5 mm Hg in
      normotensives (p = 0.026). Vascular elasticity relates to endothelial function,
      and can be measured non-invasively. At baseline and follow-up, vascular
      compliance was assessed via digital pulse wave analysis (DPA; Meridian Medical).
      After one week, pulse wave analysis showed a significant increase in large artery
      compliance (mean 23% improvement; p = 0.02) and a non-significant increase in
      small artery compliance (mean 23% improvement; p = 0.15). This study demonstrates
      blood pressure reductions, especially in patients with borderline or frank
      hypertension, as well as improved vascular compliance - an indicator of improved
      endothelial function and perfusion - after a one-week trial of sustained-release
      L-arginine. Poor endothelial function due to inadequate endothelial nitric oxide
      production is present in hypertension, as well as in numerous other aspects of
      cardiovascular disease, including angina, erectile dysfunction, cerebrovascular
      disease, and peripheral vascular disease. This is the first study showing a
      moderate dose of sustained-release L-arginine can improve endothelial function
      and blood pressure.

PMID- 16597192
TI  - Naturopathic medicine and type 2 diabetes: a retrospective analysis from an
      academic clinic.
AB  - Accurate descriptions of naturopathic medicine as a whole system of medical
      practice are rare in the literature and non-existent for type 2 diabetes.
      METHODS: Using retrospective analysis of medical records at an academic
      naturopathic outpatient clinic, data was abstracted to investigate patterns of
      patient status, details of treatment recommendations, and levels of evidence.
      RESULTS: Most naturopathic medical care for type 2 diabetes is adjunctive,
      although naturopathic physicians are qualified to fill the role of primary care
      providers. Glycemic control and other vital statistics in patients receiving
      naturopathic care are comparable to published national averages. Naturopathic
      physicians prescribe comprehensive therapeutic lifestyle change recommendations
      supported by a high level of evidence - 100 percent received dietary counseling,
      69 percent were taught stress reduction techniques, and 94 percent were
      prescribed exercise. Patients additionally received prescriptions for botanical
      and nutritional supplementation, often in combination with conventional
      medication. Analysis of individual supplement effects was not performed due to
      inadequate records. Components of treatment recommendations are often evidence
      based, with varying evidence quality. CONCLUSION: Naturopathic medicine as a
      whole medical system supplies evidence-based lifestyle recommendations as
      suggested in management guidelines for diabetes, hypertension, and hyperlipidemia
      set forth by the respective national organizations - the American Diabetes
      Association (ADA), the Joint National Committee on Hypertension (JNC-7), and the
      National Cholesterol Education Program results of the third Adult Treatment Panel
      (NCEP ATP-III). Increased research effort to determine the safety and efficacy of
      combinations of supplements or medications and supplements is warranted.
      Education of other health care providers, patients, and health policy makers
      regarding the value of the naturopathic approach in the treatment and prevention
      of type 2 diabetes is warranted, yet prospective data on efficacy must be
      collected.

PMID- 16597193
TI  - Suppression of adrenal function by low-dose prednisone: assessment with 24-hour
      urinary steroid hormone profiles--a review of five cases.
AB  - The impact of the synthetic glucocorticoid prednisone on adrenal steroid hormone
      production was examined using 24-hour urinary steroid hormone profiling. Five
      women, who were chronically taking low-dose prednisone, were tested, and the
      relevant literature was reviewed. As expected, adrenal glucocorticoid production,
      measured by urinary terminal cortisol and cortisone metabolites, was markedly
      suppressed compared to reference range values (p=0.03). Urinary cortisol and
      cortisone, reflecting circulating glucocorticoids, were decreased to a lesser
      extent than their terminal metabolites. Urinary dehydroepiandrosterone (DHEA)
      excretion was dramatically suppressed (p=0.03), while the downstream androgen
      metabolites androsterone and etiocholanolone were suppressed to a lesser extent.
      Aldosterone and tetrahydrocorticosterone production demonstrated modest
      suppression after prednisone administration, but allo-tetrahydrocorticosterone,
      which is highly sensitive to adrenocorticotropic hormone (ACTH) secretion, was
      suppressed to a greater extent. Prednisone administration results in a decrease
      in ACTH secretion by the anterior pituitary, suppressing synthesis of
      glucocorticoids, DHEA, and DHEA metabolites. Decreased glucocorticoid synthesis
      is adaptive, because prednisone is active at the glucocorticoid receptor, but
      suppression of DHEA synthesis is not mitigated by prednisone. DHEA is an
      important sex hormone precursor, neurosteroid, and endocrine and immune
      modulator; therefore, DHEA depletion may have significant adverse consequences in
      terms of sex hormone production, bone health, endocrine and immune system
      function, and neuropsychiatric status. Studies of DHEA replacement in patients
      taking prednisone for lupus demonstrate amelioration of some of these adverse
      effects.

PMID- 16597194
TI  - Coleus forskohlii. Monograph.

PMID- 16597195
TI  - L-Tryptophan. Monograph.

PMID- 16597196
TI  - Identification of anti-infective targets through comparative proteomics.

PMID- 16597199
TI  - Miconazole: a historical perspective.
AB  - Miconazole is an imidazole that has been successfully used for over 30 years for
      the treatment of superficial and cutaneous disease. This agent is distinguished
      from other azoles by possessing two mechanisms of action. The first mechanism is
      shared with other azoles and involves the inhibition of ergosterol synthesis.
      Another mechanism involves inhibition of peroxidases, which results in the
      accumulation of peroxide within the cell resulting in cell death. Susceptibility
      patterns for miconazole demonstrate that yeast fungi remain largely susceptible
      even in light of repeated exposures. Despite the release of newer azoles and
      other classes of antifungals, miconazole remains a highly prescribed treatment
      for vaginal candidiasis.

PMID- 16597200
TI  - Miltefosine: oral treatment of leishmaniasis.
AB  - The well-known problems of classic treatment of the leishmaniases with
      pentavalent antimony (reduced efficacy), difficulties of administration and
      increasing frequency and severity of adverse events have stimulated the search
      for new drugs to treat these diseases. Other injectable, oral and topical drugs
      have not been consistently effective, especially in the modern World. Beginning
      in 1998, Indian researchers conducted several trials with hexadecylphosphocholine
      (miltefosine) in patients with visceral leishmaniasis, and in 1999, clinical
      studies were initiated in Colombia for cutaneous disease. More than 2500 patients
      have been treated, including patients with diffuse cutaneous leishmaniasis,
      mucosal disease and patients coinfected with HIV. Cure rates between 91 and 100%
      were reached with a dose of 2.5 mg/kg/day for 28 days, with no difference between
      treatment-naive and relapsing patients. Mild gastrointestinal events were present
      in 35-60% of patients and 10-20% had mild transaminase and creatinine elevations.
      Miltefosine has potent leishmanicidal activity as a consequence of its
      interference in parasite metabolic pathways and the induction of apoptosis.
      Miltefosine is the first effective and safe oral agent with the potential to
      treat all major clinical presentations of leishmaniasis.

PMID- 16597201
TI  - Treatment options for visceral leishmaniasis.
AB  - This review summarizes the current developments in therapy for visceral
      leishmaniasis. With the recent introduction of new drugs, the main limits in
      reducing deaths from visceral leishmaniasis are difficulty in diagnosis in the
      field and health inequality--patients lack of access to treatment. No new drugs
      are currently in the early stages of development. There are good reasons for the
      use of combination therapy; to prevent further development of resistance against
      the limited therapeutic options available.

PMID- 16597202
TI  - Praziquantel for the treatment of schistosomiasis: its use for control in areas
      with endemic disease and prospects for drug resistance.
AB  - Praziquantel became available for the treatment of schistosomiasis and other
      trematode-inflicted diseases in the 1970s. It was revolutionary because it could
      be administered orally and had very few unwanted side effects. As a result of
      marked reductions in the price of praziquantel, the rate at which it is used has
      accelerated greatly in recent years. For the foreseeable future it will be the
      mainstay of programs designed to control schistosome-induced morbidity,
      particularly in sub-Saharan Africa where schistosomiasis is heavily endemic.
      There is currently no evidence to suggest that any schistosomes have developed
      resistance to praziquantel as a result of its widespread use. Nevertheless, while
      resistance may not pose an obvious or immediate threat to the usefulness of
      praziquantel, complacency and a failure to monitor developments may have serious
      consequences in the longer term since it will be the only drug that is readily
      available for large-scale treatment of schistosomiasis.

PMID- 16597203
TI  - New strategies to combat filariasis.
AB  - Two of the major filarial infections, lymphatic filariasis (LF) and
      onchocerciasis, affect 150 million people, while 1 billion living in endemic
      areas are at risk of infection. Public health programs to control these
      infections have successfully existed for years and have evolved from activities
      driven by the WHO into global programs with public-private partnerships.
      Currently, these programs use yearly mass application of drugs that mainly kill
      the larval stages (the microfilariae), with the aim of preventing uptake by the
      transmitting insect vectors and thus, to block transmission and reduce the
      infections to such levels that in 15-30 years from now, they will no longer pose
      a public health problem. While the programs have been very successful in general,
      there are drawbacks such as coverage being too low within the population,
      reappearance of infection by migration of infected people into controlled areas,
      targeting of a stage (the microfilaria) that does not induce pathology in LF and
      thus lowers compliance, and the potential development of drug resistance, first
      indications of which have been clearly observed in onchocerciasis. In addition,
      even without drawbacks, program scopes are not the eradication of filarial
      infections, which is, however, an ultimate goal of control activities. There is
      therefore an unequivocal call for the development of higher efficient,
      complementary chemotherapeutical approaches that lead to a long-lasting reduction
      of the pathology-inducing worm stages; that is, microfilariae in onchocerciasis
      and adult worms in LF, or to a macrofilaricidal effect. The recent discovery that
      depletion of Wolbachia endosymbionts by tetracycline antibiotics leads to long
      lasting sterility of adult female worms in onchocerciasis and a macrofilaricidal
      effect in LF fulfils these requirements. Successful regimens have already been
      published and agreed upon for use by expert panels. While these regimens are
      still too long for mass application, the antiwolbachial chemotherapy can
      currently be applied in the form of a suitable doxycycline regimen for 6 weeks
      for the treatment of individuals, and exploited in the future for the development
      of new drugs suitable for mass application. In addition, first data suggest that
      Wolbachia may also be major mediators of lymphangiogenesis and that their
      depletion is associated with reduction of lymph vessel-specific vascular
      endothelial growth factors and reduced lymph vessel size.

PMID- 16597204
TI  - Prevention of surgical site infections.
AB  - In the current era of pay-for-performance standards, the incidence of surgical
      site infections is increasingly becoming an institutional marker of quality
      assurance. Surgical site infections lead to increased morbidity and mortality in
      the surgical population and contribute to an already rising healthcare cost. As a
      result, the surgical community goes to great lengths to prevent this costly and
      occasionally lethal complication. Many practices are evidence based, however,
      many are not. In this article, the most commonly used preventive strategies in
      practice today and the evidence behind each are reviewed. In addition, an
      overview of the epidemiology, pathophysiology and microbiology of surgical site
      infections will be provided.

PMID- 16597205
TI  - Epidemiology, pathogenesis and treatment of pelvic inflammatory disease.
AB  - Pelvic inflammatory disease, the infection and inflammation of the female upper
      genital tract, is a common cause of infertility, chronic pain and ectopic
      pregnancy. Diagnosis and management are challenging, due largely to a
      polymicrobial etiology which is not fully delineated. Signs and symptoms of this
      syndrome vary widely, further complicating diagnosis and treatment. Due to the
      potential for serious sequelae, a low threshold for diagnosis and treatment is
      recommended. Since pelvic inflammatory disease has a multimicrobial etiology
      including Neisseria gonorrhoeae, Chlamydia trachomatis and anaerobic and
      mycoplasmal bacteria, treatment of pelvic inflammatory disease should be broad
      spectrum. Recent treatment trials have focused on shorter duration regimens such
      as azithromycin and monotherapies including ofloxacin, although data are sparse.
      Research comparing sequelae development by differing antimicrobial regimens is
      extremely limited, but will ultimately shape future treatment guidelines. Several
      promising short-duration and monotherapy antibiotic regimens should be evaluated
      in pelvic inflammatory disease treatment trials for compliance, microbiological
      and clinical cure, and reduction of subsequent adverse reproductive and
      gynecological morbidity.

PMID- 16597206
TI  - Spontaneous bacterial peritonitis: a therapeutic update.
AB  - Spontaneous bacterial peritonitis (SBP) is one of the main infectious
      complications of cirrhosis and occurs in 8-30% of hospitalized patients with
      ascites. SBP is characterized by infection of the ascitic fluid (AF) in the
      absence of any primary focus of intra-abdominal infection. The main route by
      which the AF becomes infected is the hematogenous route. The pathogenic mechanism
      by which infection develops is bacterial translocation from the intestinal flora
      to the mesenteric lymph nodes and from there to the bloodstream. Contributing
      factors are an increased growth of Gram-negative aerobic bacilli in the jejunum,
      changes in the intestinal barrier and in addition factors which could reduce the
      local flow of blood. For clinical diagnosis, patients with SBP may present signs
      of peritoneal irritation and pain, together with changes in gastrointestinal
      motility, sometimes with nausea, vomiting, diarrhea or ileus. Many patients,
      however, may not present any symptoms or signs as a result of the presence of
      SBP. Diagnostic paracentesis of the AF must be performed for every patient with
      cirrhosis, hospitalized with ascites. Laboratory diagnosis of SBP is carried out
      by polymorphonuclear count in the AF, together with a positive culture from the
      AF, which is characteristically monomicrobial. Escherichia coli has been the main
      bacterium isolated from AF as well as other Gram-negative bacteria from the
      Enterobacteriaceae family and Streptococcus genus. A more rapid diagnosis of SBP
      can be obtained via the use of leukocyte esterase, which is present in biological
      fluids and reacts with a component of the dipstick, changing its color. During
      the acute phase of SBP, antibiotics should be initiated promptly once the
      clinical and laboratory diagnosis of SBP has been made, before the result of AF
      culture. Cefotaxime or other third-generation cephalosporins have been considered
      the first-choice empirical antibiotics in the treatment of cirrhotic patients
      with SBP, and is efficacious in approximately 90% of cases. Broad-spectrum
      quinolones, which are almost completely absorbed after oral administration and
      diffuse rapidly through the AF, are currently used for oral treatment of
      uncomplicated SBP. Patients who have already had a previous episode of SBP, with
      a 69% probability of recurrence within a year, will benefit from prophylactic
      treatment. Cirrhotic patients with a high risk of SBP and other infections, such
      as those with gastrointestinal bleeding, also benefit from primary prophylaxis
      and norfloxacin has been used with success.

PMID- 16597207
TI  - Probiotics: their role in the treatment and prevention of disease.
AB  - A probiotic is a "live microbial food ingredients that, when ingested in
      sufficient quantities, exerts health benefits on the consumer". Probiotics exert
      their benefits through several mechanisms; they prevent colonization, cellular
      adhesion and invasion by pathogenic organisms, they have direct antimicrobial
      activity and they modulate the host immune response. The strongest evidence for
      the clinical effectiveness of probiotics has been in their use for the prevention
      of symptoms of lactose intolerance, treatment of acute diarrhea, attenuation of
      antibiotic-associated gastrointestinal side effects and the prevention and
      treatment of allergy manifestations. More research needs to be carried out to
      clarify conflicting findings on the use of probiotics for prevention of
      travelers' diarrhea, infections in children in daycare and dental caries, and
      elimination of nasal colonization with potentially pathogenic bacteria. Promising
      ongoing research is being conducted on the use of probiotics for the treatment of
      Clostridium difficile colitis, treatment of Helicobacter pylori infection,
      treatment of inflammatory bowel disease and prevention of relapse, treatment of
      irritable bowel syndrome, treatment of intestinal inflammation in cystic fibrosis
      patients, and prevention of necrotizing enterocolitis in premature infants.
      Finally, areas of future research include the use of probiotics for the treatment
      of rheumatoid arthritis, prevention of cancer and the treatment of graft-versus
      host disease in bone marrow transplant recipients.

PMID- 16597208
TI  - Smallpox antiviral drug development: satisfying the animal efficacy rule.
AB  - Concerns over the potential use of variola virus as a biological weapon have
      prompted new interest in the development of small molecule therapeutics to
      prevent and treat smallpox infection. Since smallpox is no longer endemic, human
      clinical trials designed to link antiviral efficacy to clinical outcome have been
      supplanted by antiviral efficacy evaluations in animal models of orthopoxvirus
      disease. This poses a unique challenge for drug development; how can animal
      efficacy data with a surrogate virus be used to establish clinical correlates
      predictive of human disease outcome? This review will examine the properties of
      selected animal models that are being used to evaluate poxvirus antiviral drug
      candidates, and discuss how data from these models can be used to link drug
      efficacy to clinical correlates of human disease.

PMID- 16597209
TI  - Potential antivirals and antiviral strategies against SARS coronavirus
      infections.
AB  - There are a number of antivirals as well as antiviral strategies that could be
      envisaged to prevent or treat severe acute respiratory syndrome (SARS) (or
      similar) coronavirus (CoV) infections. Targets for the prophylactic or
      therapeutic interventions include interaction of the spike (S) glycoprotein (S1
      domain) with the host cell receptor, fusion of the S2 domain with the host cell
      membrane, processing of the replicase polyproteins by the virus-encoded proteases
      (3C-like cysteine protease [3CLpro] and papain-like cysteine protease) and other
      virus-encoded enzymes such as the NTPase/helicase and RNA-dependent RNA
      polymerase. Human monoclonal antibody blocking S1 may play an important role in
      the immunoprophylaxis of SARS. Fusion inhibitors reminiscent of enfuvirtide in
      the case of HIV may also be developed for SARS-CoV. Various peptidomimetic and
      nonpeptidic inhibitors of 3CLpro have been described, the best ones inhibiting
      SARS-CoV replication with a selectivity index greater than 1000. Human
      interferons, in particular alpha- and beta-interferon, as well as short
      interfering RNAs could further be pursued for the control of SARS. Various other
      compounds, often with an ill-defined mode of action but selectivity indexes up to
      100, have been reported to exhibit in vitro activity against SARS-CoV:
      valinomycin, glycopeptide antibiotics, plant lectins, hesperetin, glycyrrhizin,
      aurintricarboxylic acid, chloroquine, niclosamide, nelfinavir and calpain
      inhibitors.

PMID- 16597210
TI  - HIV/AIDS pathogenesis and treatment options focusing on the viral entry
      inhibitors.
AB  - The advent of highly active antiretroviral therapy (HAART) has revolutionized the
      treatment of HIV. A wide variety of antiretroviral agents are now available,
      allowing patients and physicians a choice of effective therapy. However, drug
      resistance and toxicities are emerging as major treatment challenges in the HAART
      era. The development of agents within existing and novel antiretroviral classes
      remains paramount in order to preserve the reduced morbidity and mortality we
      have come to expect from HAART use. This article details the development of the
      HIV epidemic, reviewing current and future treatment strategies, and
      concentrating upon the viral entry inhibitors.

PMID- 16597211
TI  - Japanese encephalitis: development of new candidate vaccines.
AB  - Japanese encephalitis (JE) is the most common form of viral encephalitis that
      appears in the form of frequent epidemics of brain fever throughout Southeast
      Asia, China and India. The disease is caused by a Flavivirus named Japanese
      encephalitis virus that is spread to humans by mosquitoes. An internationally
      approved mouse brain-derived inactivated vaccine has been available that is
      relatively expensive, gives immunity of uncertain duration and is not completely
      safe. Cell culture-derived inactivated and attenuated JE vaccines are in use in
      China, but these are not produced as per the norms acceptable in most countries.
      Several new promising JE vaccine candidates have been developed, some of which
      are under different stages of clinical evaluation. These new candidate JE
      vaccines have the potential to generate long-lasting immunity at low cost.

PMID- 16597212
TI  - Echinocandin antifungals: review and update.
AB  - The echinocandins are a new and unique class of antifungal agents that act on the
      fungal cell wall by way of noncompetitive inhibition of the synthesis of 1,3-beta
      glucans. All agents of this class are of parenteral formulation, with no oral
      preparations available. Caspofungin (Cancidas) was the first approved
      echinocandin, followed recently by micafungin (Mycamine) and anidulafungin
      (Eraxis). The precise role of the echinocandins in the antifungal armamentarium
      is still unfolding. Caspofungin is approved for the treatment of candidal
      esophagitis and candidemia, salvage therapy of Aspergillus infections and for
      empirical therapy of febrile neutropenia. Micafungin is likewise approved for
      candidal esophagitis, in addition to antifungal prophylaxis for hematopoietic
      stem cell transplant recipients. Anidulafungin is also approved for treatment of
      candidal esophagitis, as well as therapy of candidemia. There has been anecdotal
      use of these agents to treat less common fungal pathogens, as well as limited use
      as a component of combination antifungal therapy. The echinocandins are an
      important addition to the antifungal armamentarium in the treatment of fungal
      infections in both immunocompromised patients and those with normal immunity.

PMID- 16597213
TI  - School connectedness is an underemphasized parameter in adolescent mental health:
      results of a community prediction study.
AB  - There is limited prospective research on the relation between school
      connectedness (i.e., the extent to which students feel accepted, valued,
      respected, and included in the school) and mental health symptoms in adolescents.
      A sample of 2,022 students (999 boys and 1,023 girls) ages 12 to 14 years were
      measured at 2 time points (12 months apart) on school connectedness and mental
      health symptoms (general functioning, depression, and anxiety symptoms). School
      connectedness correlated extensively with concurrent mental health symptoms at
      both time points (between 38% and 55% covariation with depression, 26% to 46%
      with general functioning, and 9% and 16% for anxiety symptoms). Using
      hierarchical linear modeling, school connectedness also predicted depressive
      symptoms 1 year later for both boys and girls, anxiety symptoms for girls, and
      general functioning for boys, even after controlling for prior symptoms. The
      reverse, however, was not true: Prior mental health symptoms did not predict
      school connectedness 1 year later when controlling for prior school
      connectedness. Results suggest a stronger than previously reported association
      with school connectedness and adolescent depressive symptoms in particular and a
      predictive link from school connectedness to future mental health problems.

PMID- 16597214
TI  - Behavioral family intervention for children with developmental disabilities and
      behavioral problems.
AB  - The outcomes of a randomized clinical trial of a new behavioral family
      intervention, Stepping Stones Triple P, for preschoolers with developmental and
      behavior problems are presented. Forty-eight children with developmental
      disabilities participated, 27 randomly allocated to an intervention group and 20
      to a wait-list control group. Parents completed measures of parenting style and
      stress, and independent observers assessed parent-child interactions. The
      intervention was associated with fewer child behavior problems reported by
      mothers and independent observers, improved maternal and paternal parenting
      style, and decreased maternal stress. All effects were maintained at 6-month
      follow-up.

PMID- 16597215
TI  - Antecedents of toddler aggression: dysfunctional parenting in mother-toddler
      dyads.
AB  - Aggression is stable as early as 2 years of age and predicts many negative adult
      outcomes. Although longitudinal predictors of child aggression have been
      identified, information is lacking regarding the proximal precursors of toddlers'
      aggression. During a 30-min interaction, 54 mother-toddler dyads were observed.
      Toddlers were categorized as aggressive or nonaggressive based on whether they
      exhibited aggression toward their mothers within the interaction. Most toddlers
      in both groups escalated from mild to more severe forms of misbehavior. Mothers
      of aggressive toddlers displayed more lax and over-reactive discipline when
      addressing misbehaviors that preceded aggression than did mothers of
      nonaggressive toddlers. Mothers of aggressive toddlers either ignored or attended
      neutrally or positively to the aggression. Implications for parenting
      interventions are discussed.

PMID- 16597216
TI  - Road-crossing safety in virtual reality: a comparison of adolescents with and
      without ADHD.
AB  - This study investigated the potential accident-proneness of adolescents with
      attention deficit hyperactivity disorder (ADHD) in a hazardous road-crossing
      environment. An immersive virtual reality traffic gap-choice task was used to
      determine whether ADHD adolescents show more unsafe road-crossing behavior than
      controls. Participants (ages 13 to 17) were identified with (n = 24) or without
      (n = 24) ADHD according to a standardized protocol (Schedule for Affective
      Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version
      and Conners' Scales), with equal number of boys (n = 12) and girls (n = 12) in
      each group. ADHD adolescents did not take stimulant medication on the day of
      testing. Participants with ADHD had a lower margin of safety, walked slower,
      underutilized the available gap in incoming traffic, showed greater variability
      in road-crossing behavior, and evidenced twice as many collisions as compared to
      controls. No sex differences were found. Virtual reality may help identify and
      educate those at higher risk of being involved in dangerous traffic situations.

PMID- 16597218
TI  - An independent effectiveness trial of multisystemic therapy with juvenile justice
      youth.
AB  - This study examines the effectiveness of an evidence-based practice,
      multisystemic therapy (MST), conducted in a real-world mental health setting with
      juvenile justice involved youth and their families. Importantly, this is the
      first randomized clinical trial of MST with juvenile offenders in the United
      States conducted without direct oversight by the model developers. This study
      reports outcomes achieved for 93 youth randomly assigned to MST or treatment as
      usual (TAU) services through 18-month follow-up posttreatment for offense data
      and 6-month follow-up posttreatment for ratings of the Child and Adolescent
      Functional Assessment Scale (CAFAS). Outcomes include significant reduction in
      rearrest and improvement in 4 areas of functioning measured by the CAFAS for
      youth who received MST. Implications for delivery of empirically supported
      treatments in real-world settings are discussed.

PMID- 16597217
TI  - Antisocial behaviors moderate the deviant peer pathway to substance use in
      children with ADHD.
AB  - This study evaluated the interplay of attention deficit hyperactivity disorder
      (ADHD) symptom severity, deviant peer group affiliation, oppositional defiant
      disorder (ODD), and conduct disorder (CD) as risk factors among 142 adolescents
      with childhood ADHD. Deviant peer affiliation mediated the relation between
      childhood ADHD symptoms and 6 substance use and abuse variables. Moreover,
      moderated mediation analyses found that for children with high levels of ODD and
      CD symptoms, the mediated effect of ADHD through deviant peer affiliation was
      significant; however, for children with low levels of ODD and CD symptoms, this
      mediated effect was weak and nonsignificant. Results suggest that children with
      severe ADHD symptomatology and comorbid antisocial behavior are at highest risk
      for peer-mediated substance use in adolescence.

PMID- 16597219
TI  - Estimating genetic and environmental influences on depressive symptoms in
      adolescence: differing effects on higher and lower levels of symptoms.
AB  - We estimate the relative effect sizes of genetic and environmental influences on
      both higher and lower levels of depressive symptoms with attention to persistence
      over a 1-year period in the genetically informative subsample of adolescents
      participating in the National Longitudinal Study of Adolescent Health (Add
      Health). Shared environmental effects were significant for persistent higher
      levels of depressive symptoms but not nonpersistent symptoms. Genetic effects
      were significant for both persistent and nonpersistent lower levels of depressive
      symptoms. Nongenetic factors that promote similarity between siblings for high
      levels of depressive symptoms are important and should be considered in both
      etiological and applied research. Genetic contributions to lack of susceptibility
      to depression should be considered in biological models of depression
      suppression.

PMID- 16597220
TI  - Risk factors for conduct problems and depressive symptoms in a cohort of
      Ukrainian children.
AB  - Potential risk factors for conduct problems and depressive symptoms were tested
      in a cohort of 10- to 12-year-old Ukrainian children (N = 544, 47.6% male). Risk
      factors examined were child emotional lability, child attention problems, poor
      mother-child communication, coercive maternal discipline, maternal depression,
      and low marital satisfaction. Results indicated that poor mother-child
      communication was related to conduct problems and depressive symptoms for both
      boys and girls. In addition, conduct problems and depression were associated with
      attention problems for boys and with low marital satisfaction for girls.
      Emotional lability was related specifically to conduct problems, and maternal
      punishment was related specifically to depressive symptoms.

PMID- 16597221
TI  - The timing of parent and child depression: a hopelessness theory perspective.
AB  - This study examined whether children's inferential styles moderate the
      association between the onset of depressive symptoms in children and their
      parents. To provide a powerful test of our hypotheses, we utilized a high-risk
      sample (parents with a history of major depressive episodes and their children)
      and a multiwave longitudinal design. During the initial assessment, 140 children
      (ages 6 to 14) completed measures assessing depressogenic inferential styles.
      Parents and children also completed measures assessing current level of
      depressive symptoms. Following the initial assessment, children and parents were
      contacted every 6 weeks for the next year to complete measures assessing
      depressive symptoms. The results of hierarchical linear modeling analyses
      indicated that children who exhibited depressogenic inferential styles reported
      greater elevations in depressive symptoms following elevations in their parent's
      level of depressive symptoms than did children who did not exhibit such styles.
      The strength of this association was greater in girls.

PMID- 16597222
TI  - A prospective test of the hopelessness theory of depression in children.
AB  - Providing a developmental extension of the cognitive theories of depression,
      researchers and theorists have suggested that during early to middle childhood,
      attributional styles may mediate rather than moderate the association between
      negative life events and the development of depression. Within the context of the
      hopelessness theory of depression, we tested this hypothesis in a 6-month
      longitudinal study of 4th- and 5th-grade children. Using path analysis, we found
      support for the mediating role of attributional styles among both 4th and 5th
      graders. Supporting recent refinements in the hopelessness theory, the best
      fitting mediation model was one in which depressive symptoms exhibited reciprocal
      relations with the other variables. Specifically, attributional styles partially
      mediated the link between verbal victimization and residual change in depressive
      symptoms. In addition, initial depressive symptoms predicted negative changes in
      children's attributional styles and increases in verbal victimization across the
      follow-up. Contrary to our hypothesis, we also found support for the moderating
      role of attributional styles, although this was significant only among 5th
      graders.

PMID- 16597223
TI  - Dating, sexual activity, and well-being in Italian adolescents.
AB  - Associations among dating, sexual activity, gender, and adjustment were
      investigated in 2,273 Italian adolescents (54% female, ages 14 to 19 years)
      attending public high schools. After controlling for age and type of school
      attended, both being in a dating relationship and being male were associated with
      less alienation, more positive views of the self, and higher general expectations
      for success. Sexual activity interacted with both gender and dating status in
      predicting feelings of depression. For boys, there were no differences between
      youth who were sexually active and youth who were not; however, sexually active
      girls had higher levels of depressive symptoms than girls who were not sexually
      active. Among youth who were not sexually active, there were small differences
      between daters and nondaters; among sexually active youth, daters had lower
      levels of depression than nondaters. Gender differences in adolescents'
      experience of dating and sexual relationships and implications for adjustment are
      discussed.

PMID- 16597224
TI  - Pursuit of muscularity in adolescent boys: relations among biopsychosocial
      variables and clinical outcomes.
AB  - Adolescent boys (n = 269) were assessed for levels of several risky behaviors
      related to the pursuit of muscularity, including substance use (anabolic
      steroids, prohormones, and ephedrine) dieting to gain weight, and symptoms of
      muscle dysmorphia (MD). The association between these behaviors and a variety of
      putative biological, psychological, and social risk factors were also evaluated.
      Concerning rates for lifetime use of steroids (2.6%), prohormones (4.5%), and
      ephedrine (6%) were found. Multiple regression analyses indicated that MD and
      sports participation significantly predicted substance use. Body dissatisfaction
      and body mass index were significant predictors of dieting to gain weight.
      Additionally, negative affect, media influence, and sports participation
      predicted symptoms of MD.

PMID- 16597225
TI  - Social anxiety and self-evaluation of social performance in a nonclinical sample
      of children.
AB  - In an investigation of socially anxious children's social behavior and self
      evaluation, 28 high socially anxious and 28 low socially anxious children, ages
      11 to 13 years, appraised their performance before and after participating in a
      role-play task. Half of the children were given video feedback prior to giving
      their posttask self-evaluations. High socially anxious children anticipated
      poorer performance on the role-play task, and some group differences in observed
      social performance were evident. Self-evaluations from video feedback only
      improved for the high socially anxious children who displayed more eye contact,
      gave longer verbal responses, and used more constructive verbal strategies in the
      role-play scenarios.

PMID- 16597226
TI  - Factor structure and validity of the parenting stress index-short form.
AB  - The psychometric properties of the Parenting Stress Index-Short Form (PSI-SF)
      were examined in a sample of 185 mothers and fathers. Factor analysis revealed 2
      reasonably distinct factors involving parental distress and dysfunctional parent
      child interactions. Both scales were internally consistent, and these scales were
      correlated with measures of parent psychopathology, parental perceptions of child
      adjustment, and observed parent and child behavior. PSI-SF scores were related to
      parent reports of child behavior 1 year later, and the Childrearing Stress
      subscale was a significant predictor of a parental history of abuse.

PMID- 16597227
TI  - Relation of positive and negative parenting to children's depressive symptoms.
AB  - This study examined the combined and cumulative effects of supportive-positive
      and harsh-negative parenting behaviors on children's depressive symptoms. A
      diverse sample of 515 male and female elementary and middle school students (ages
      7 to 11) and their parents provided reports of the children's depressive
      symptoms. Parents provided self-reports of supportive-positive and harsh-negative
      parenting behaviors. Structural equation modeling indicated that supportive
      positive and harsh-negative parenting behaviors were nearly orthogonal dimensions
      of parenting and both related to children's depressive symptoms. Supportive
      positive parenting behaviors did not moderate the relation between harsh-negative
      parenting behaviors and children's depressive symptoms. Results have implications
      for family intervention and prevention strategies.

PMID- 16597228
TI  - Observational measures of parenting in anxious and nonanxious mothers: does type
      of task matter?
AB  - This study examined the relation between type of parent-child interaction task
      and parenting behaviors among a predominantly African American community-based
      sample. Twenty-five anxious and matched nonanxious (N = 50) mothers were
      videotaped with their children (M age = 5.8 years) engaging in both a structured
      and unstructured task. Blind raters coded 3 parent behaviors hypothesized to play
      a role in the development of child anxiety: overcontrol, anxious behavior, and
      criticism. Results indicated that higher levels of overcontrol, anxious behavior,
      and criticism were found in the structured compared to unstructured task. Levels
      of criticism, among anxious mothers only, were significantly correlated across
      tasks. Results suggest that situation specific aspects of parent-child
      interaction tasks may influence parenting behaviors. These findings help explain
      variations in observational research in the anxiety literature and highlight the
      need for careful selection of parent-child tasks in future research.

PMID- 16597231
TI  - Efficient algorithms for detecting signaling pathways in protein interaction
      networks.
AB  - The interpretation of large-scale protein network data depends on our ability to
      identify significant substructures in the data, a computationally intensive task.
      Here we adapt and extend efficient techniques for finding paths and trees in
      graphs to the problem of identifying pathways in protein interaction networks. We
      present linear-time algorithms for finding paths and trees in networks under
      several biologically motivated constraints. We apply our methodology to search
      for protein pathways in the yeast protein-protein interaction network. We
      demonstrate that our algorithm is capable of reconstructing known signaling
      pathways and identifying functionally enriched paths and trees in an unsupervised
      manner. The algorithm is very efficient, computing optimal paths of length 8
      within minutes and paths of length 10 in about three hours.

PMID- 16597229
TI  - Trait affectivity and non-referred adolescent conduct problems.
AB  - This study examined for profiles of positive trait affectivity (PA) and negative
      trait affectivity (NA) associated with adolescent conduct problems. Prior trait
      affectivity research has been relatively biased toward the assessment of adults
      and internalizing symptomatology. Consistent with recent developmental modeling
      of antisocial behavior, this study proposed that conduct problems are uniquely
      associated with 2 PA-NA profiles (i.e., high PA-high NA and low PA-low NA). A non
      referred sample of 109 adolescents ages 12 to 19 was recruited to assess the
      independent relations between rating scale measures of the PA-NA dimensions and
      conduct problems, controlling for related internalizing (anxiety and depression)
      and externalizing (hyperactivity-impulsivity) symptomatology. The results
      generally confirmed the proposed interaction between the PA-NA dimensions in the
      prediction of adolescent conduct problems.

PMID- 16597232
TI  - Towards an integrated protein-protein interaction network: a relational Markov
      network approach.
AB  - Protein-protein interactions play a major role in most cellular processes. Thus,
      the challenge of identifying the full repertoire of interacting proteins in the
      cell is of great importance and has been addressed both experimentally and
      computationally. Today, large scale experimental studies of protein interactions,
      while partial and noisy, allow us to characterize properties of interacting
      proteins and develop predictive algorithms. Most existing algorithms, however,
      ignore possible dependencies between interacting pairs and predict them
      independently of one another. In this study, we present a computational approach
      that overcomes this drawback by predicting protein-protein interactions
      simultaneously. In addition, our approach allows us to integrate various protein
      attributes and explicitly account for uncertainty of assay measurements. Using
      the language of relational Markov networks, we build a unified probabilistic
      model that includes all of these elements. We show how we can learn our model
      properties and then use it to predict all unobserved interactions simultaneously.
      Our results show that by modeling dependencies between interactions, as well as
      by taking into account protein attributes and measurement noise, we achieve a
      more accurate description of the protein interaction network. Furthermore, our
      approach allows us to gain new insights into the properties of interacting
      proteins.

PMID- 16597233
TI  - A probabilistic methodology for integrating knowledge and experiments on
      biological networks.
AB  - Biological systems are traditionally studied by focusing on a specific subsystem,
      building an intuitive model for it, and refining the model using results from
      carefully designed experiments. Modern experimental techniques provide massive
      data on the global behavior of biological systems, and systematically using these
      large datasets for refining existing knowledge is a major challenge. Here we
      introduce an extended computational framework that combines formalization of
      existing qualitative models, probabilistic modeling, and integration of high
      throughput experimental data. Using our methods, it is possible to interpret
      genomewide measurements in the context of prior knowledge on the system, to
      assign statistical meaning to the accuracy of such knowledge, and to learn
      refined models with improved fit to the experiments. Our model is represented as
      a probabilistic factor graph, and the framework accommodates partial measurements
      of diverse biological elements. We study the performance of several probabilistic
      inference algorithms and show that hidden model variables can be reliably
      inferred even in the presence of feedback loops and complex logic. We show how to
      refine prior knowledge on combinatorial regulatory relations using hypothesis
      testing and derive p-values for learned model features. We test our methodology
      and algorithms on a simulated model and on two real yeast models. In particular,
      we use our method to explore uncharacterized relations among regulators in the
      yeast response to hyper-osmotic shock and in the yeast lysine biosynthesis
      system. Our integrative approach to the analysis of biological regulation is
      demonstrated to synergistically combine qualitative and quantitative evidence
      into concrete biological predictions.

PMID- 16597234
TI  - Pairwise alignment of protein interaction networks.
AB  - With an ever-increasing amount of available data on protein-protein interaction
      (PPI) networks and research revealing that these networks evolve at a modular
      level, discovery of conserved patterns in these networks becomes an important
      problem. Although available data on protein-protein interactions is currently
      limited, recently developed algorithms have been shown to convey novel biological
      insights through employment of elegant mathematical models. The main challenge in
      aligning PPI networks is to define a graph theoretical measure of similarity
      between graph structures that captures underlying biological phenomena
      accurately. In this respect, modeling of conservation and divergence of
      interactions, as well as the interpretation of resulting alignments, are
      important design parameters. In this paper, we develop a framework for
      comprehensive alignment of PPI networks, which is inspired by
      duplication/divergence models that focus on understanding the evolution of
      protein interactions. We propose a mathematical model that extends the concepts
      of match, mismatch, and gap in sequence alignment to that of match, mismatch, and
      duplication in network alignment and evaluates similarity between graph
      structures through a scoring function that accounts for evolutionary events. By
      relying on evolutionary models, the proposed framework facilitates interpretation
      of resulting alignments in terms of not only conservation but also divergence of
      modularity in PPI networks. Furthermore, as in the case of sequence alignment,
      our model allows flexibility in adjusting parameters to quantify underlying
      evolutionary relationships. Based on the proposed model, we formulate PPI network
      alignment as an optimization problem and present fast algorithms to solve this
      problem. Detailed experimental results from an implementation of the proposed
      framework show that our algorithm is able to discover conserved interaction
      patterns very effectively, in terms of both accuracies and computational cost.

PMID- 16597235
TI  - GenRate: a generative model that reveals novel transcripts in genome-tiling
      microarray data.
AB  - Genome-wide microarray designs containing millions to hundreds of millions of
      probes are available for a variety of mammals, including mouse and human. These
      genome tiling arrays can potentially lead to significant advances in science and
      medicine, e.g., by indicating new genes and alternative primary and secondary
      transcripts. While bottom-up pattern matching techniques (e.g., hierarchical
      clustering) can be used to find gene structures in microarray data, we believe
      the many interacting hidden variables and complex noise patterns more naturally
      lead to an analysis based on generative models. We describe a generative model of
      tiling data and show how the sum-product algorithm can be used to infer
      hybridization noise, probe sensitivity, new transcripts, and alternative
      transcripts. The method, called GenRate, maximizes a global scoring function that
      enables multiple transcripts to compete for ownership of putative probes. We
      apply GenRate to a new exon tiling dataset from mouse chromosome 4 and show that
      it makes significantly more predictions than a previously described hierarchical
      clustering method at the same false positive rate. GenRate correctly predicts
      many known genes and also predicts new gene structures. As new problems arise,
      additional hidden variables can be incorporated into the model in a principled
      fashion, so we believe that GenRate will prove to be a useful tool in the new era
      of genome-wide tiling microarray analysis.

PMID- 16597236
TI  - Efficient calculation of interval scores for DNA copy number data analysis.
AB  - DNA amplifications and deletions characterize cancer genome and are often related
      to disease evolution. Microarray-based techniques for measuring these DNA copy
      number changes use fluorescence ratios at arrayed DNA elements (BACs, cDNA, or
      oligonucleotides) to provide signals at high resolution, in terms of genomic
      locations. These data are then further analyzed to map aberrations and boundaries
      and identify biologically significant structures. We develop a statistical
      framework that enables the casting of several DNA copy number data analysis
      questions as optimization problems over real-valued vectors of signals. The
      simplest form of the optimization problem seeks to maximize phi(I) =
      Sigmanu(i)/radical|I| over all subintervals I in the input vector. We present and
      prove a linear time approximation scheme for this problem, namely, a process with
      time complexity O (nepsilon(-2)) that outputs an interval for which phi(I) is at
      least Opt/alpha(epsilon), where Opt is the actual optimum and alpha(epsilon) -->
      1 as epsilon --> 0. We further develop practical implementations that improve the
      performance of the naive quadratic approach by orders of magnitude. We discuss
      properties of optimal intervals and how they apply to the algorithm performance.
      We benchmark our algorithms on synthetic as well as publicly available DNA copy
      number data. We demonstrate the use of these methods for identifying aberrations
      in single samples as well as common alterations in fixed sets and subsets of
      breast cancer samples.

PMID- 16597237
TI  - RIBRA--an error-tolerant algorithm for the NMR backbone assignment problem.
AB  - We develop an iterative relaxation algorithm called RIBRA for NMR protein
      backbone assignment. RIBRA applies nearest neighbor and weighted maximum
      independent set algorithms to solve the problem. To deal with noisy NMR spectral
      data, RIBRA is executed in an iterative fashion based on the quality of spectral
      peaks. We first produce spin system pairs using the spectral data without missing
      peaks, then the data group with one missing peak, and finally, the data group
      with two missing peaks. We test RIBRA on two real NMR datasets, hbSBD and hbLBD,
      and perfect BMRB data (with 902 proteins) and four synthetic BMRB data which
      simulate four kinds of errors. The accuracy of RIBRA on hbSBD and hbLBD are 91.4%
      and 83.6%, respectively. The average accuracy of RIBRA on perfect BMRB datasets
      is 98.28%, and 98.28%, 95.61%, 98.16%, and 96.28% on four kinds of synthetic
      datasets, respectively.

PMID- 16597238
TI  - A high-throughput approach for associating MicroRNAs with their activity
      conditions.
AB  - Plant microRNAs (miRNAs) are short RNA sequences that bind to target mRNAs and
      change their expression levels by redirecting their stabilities and marking them
      for cleavage. In Arabidopsis thaliana, microRNAs have been shown to regulate
      development and are believed to impact expression both under various conditions,
      such as stress and stimuli, as well as in specific tissue types. We present a
      high throughput approach for associating between microRNAs and conditions in
      which they act, using novel statistical and algorithmic techniques. Our new tool,
      miRNAXpress, at first computes a (binary) matrix T denoting the potential targets
      of microRNAs. Then, using T and an additional predefined matrix X indicating
      expression of genes under various conditions, it produces a new matrix that
      predicts associations between microRNAs and the conditions in which they act.
      Thus, the program comprises two main modules that work in tandem to compute the
      desired output. The first is an efficient target prediction engine that predicts
      mRNA targets of query microRNAs by evaluating the optimal duplex that could be
      formed between the two: given a short query RNA, a long target RNA, and a
      predefined energy cut-off threshold, the program finds and reports all putative
      binding sites of the query RNA in the target RNA with hybridization energy
      bounded by the predefined threshold. The second module realizes an association
      operation that is computed by a method which relies on an efficient t-test to
      compute the associations. The calculation of the matrix of microRNAs and their
      potential targets is the computationally intensive part of the work done by
      miRNAXpress, and therefore an efficient algorithm for this portion facilitates
      the entire process. Thus, the target prediction engine is based on an efficient
      approximate hybridization search algorithm whose efficiency is the result of
      utilizing the sparsity of the search space without sacrificing the optimality of
      the results. The time complexity of this algorithm is almost linear in the size
      of a sparse set of locations where base-pairs are stacked at a height of three or
      more. Thus miRNAXpress is a novel tool for associating between microRNAs and the
      conditions in which they act. We employed it to conduct a study, using the plant
      Arabidopsis thaliana as our model organism. By applying miRNAXpress to 98
      microRNAs and 380 conditions, some biologically interesting and statistically
      strong relations were discovered. For example, mir159C activity is possibly a
      factor in the misresponse of nph4 mutants to phototropic stimulations.

PMID- 16597239
TI  - RNA-RNA interaction prediction and antisense RNA target search.
AB  - Recent studies demonstrating the existence of special noncoding "antisense" RNAs
      used in post transcriptional gene regulation have received considerable
      attention. These RNAs are synthesized naturally to control gene expression in C.
      elegans, Drosophila, and other organisms; they are known to regulate plasmid copy
      numbers in E. coli as well. Small RNAs have also been artificially constructed to
      knock out genes of interest in humans and other organisms for the purpose of
      finding out more about their functions. Although there are a number of algorithms
      for predicting the secondary structure of a single RNA molecule, no such
      algorithm exists for reliably predicting the joint secondary structure of two
      interacting RNA molecules or measuring the stability of such a joint structure.
      In this paper, we describe the RNA-RNA interaction prediction (RIP) problem
      between an antisense RNA and its target mRNA and develop efficient algorithms to
      solve it. Our algorithms minimize the joint free energy between the two RNA
      molecules under a number of energy models with growing complexity. Because the
      computational resources needed by our most accurate approach is prohibitive for
      long RNA molecules, we also describe how to speed up our techniques through a
      number of heuristic approaches while experimentally maintaining the original
      accuracy. Equipped with this fast approach, we apply our method to discover
      targets for any given antisense RNA in the associated genome sequence.

PMID- 16597240
TI  - Consensus folding of unaligned RNA sequences revisited.
AB  - As one of the earliest problems in computational biology, RNA secondary structure
      prediction (sometimes referred to as "RNA folding") problem has attracted
      attention again, thanks to the recent discoveries of many novel non-coding RNA
      molecules. The two common approaches to this problem are de novo prediction of
      RNA secondary structure based on energy minimization and the consensus folding
      approach (computing the common secondary structure for a set of unaligned RNA
      sequences). Consensus folding algorithms work well when the correct seed
      alignment is part of the input to the problem. However, seed alignment itself is
      a challenging problem for diverged RNA families. In this paper, we propose a
      novel framework to predict the common secondary structure for unaligned RNA
      sequences. By matching putative stacks in RNA sequences, we make use of both
      primary sequence information and thermodynamic stability for prediction at the
      same time. We show that our method can predict the correct common RNA secondary
      structures even when we are given only a limited number of unaligned RNA
      sequences, and it outperforms current algorithms in sensitivity and accuracy.

PMID- 16597241
TI  - Efficient q-gram filters for finding all epsilon-matches over a given length.
AB  - Fast and exact comparison of large genomic sequences remains a challenging task
      in biosequence analysis. We consider the problem of finding all epsilon-matches
      between two sequences, i.e., all local alignments over a given length with an
      error rate of at most epsilon. We study this problem theoretically, giving an
      efficient q-gram filter for solving it. Two applications of the filter are also
      discussed, in particular genomic sequence assembly and BLAST-like sequence
      comparison. Our results show that the method is 25 times faster than BLAST, while
      not being heuristic.

PMID- 16597242
TI  - A polynomial time solvable formulation of multiple sequence alignment.
AB  - Since traditional multiple alignment formulations are NP-hard, heuristics are
      commonly employed to find acceptable alignments with no guaranteed performance
      bound. This causes a substantial difficulty in understanding what the resulting
      alignment means and in assessing the quality of these alignments. We propose an
      alternative formulation of multiple alignment based on the idea of finding a
      multiple alignment of k sequences which preserves k - 1 pairwise alignments as
      specified by edges of a given tree. Although it is well known that such a
      preserving alignment always exists, it did not become a mainstream method for
      multiple alignment since it seems that a lot of information is lost from ignoring
      pairwise similarities outside the tree. In contrast, by using pairwise alignments
      that incorporate consistency information from other sequences, we show that it is
      possible to obtain very good accuracy with the preserving alignment formulation.
      We show that a reasonable objective function to use is to find the shortest
      preserving alignment, and, by a reduction to a graph-theoretic problem, that the
      problem of finding the shortest preserving multiple alignment can be solved in
      polynomial time. We demonstrate the success of this approach on three sets of
      benchmark multiple alignments by using consistency-based pairwise alignments from
      the first stage of two of the best performing progressive alignment algorithms
      TCoffee and ProbCons and replace the second heuristic progressive step of these
      algorithms by the exact preserving alignment step. We apply this strategy to
      TCoffee and show that our approach outperforms TCoffee on two of the three test
      sets. We apply the strategy to a variant of ProbCons with no iterative
      refinements and show that our approach achieves similar or better accuracy except
      on one test set. We also compare our performance to ProbCons with iterative
      refinements and show that our approach achieves similar or better accuracy on
      many subcategories even without further refinements. The most important advantage
      of the preserving alignment formulation is that we are certain that we can solve
      the problem in polynomial time without using a heuristic. A software program
      implementing this approach (PSAlign) is available at
      http://faculty.cs.tamu.edu/shsze/psalign.

PMID- 16597243
TI  - A hybrid micro-macroevolutionary approach to gene tree reconstruction.
AB  - Gene family evolution is determined by microevolutionary processes (e.g., point
      mutations) and macroevolutionary processes (e.g., gene duplication and loss), yet
      macroevolutionary considerations are rarely incorporated into gene phylogeny
      reconstruction methods. We present a dynamic program to find the most
      parsimonious gene family tree with respect to a macroevolutionary optimization
      criterion, the weighted sum of the number of gene duplications and losses. The
      existence of a polynomial delay algorithm for duplication/loss phylogeny
      reconstruction stands in contrast to most formulations of phylogeny
      reconstruction, which are NP-complete. We next extend this result to obtain a two
      phase method for gene tree reconstruction that takes both micro- and
      macroevolution into account. In the first phase, a gene tree is constructed from
      sequence data, using any of the previously known algorithms for gene phylogeny
      construction. In the second phase, the tree is refined by rearranging regions of
      the tree that do not have strong support in the sequence data to minimize the
      duplication/lost cost. Components of the tree with strong support are left
      intact. This hybrid approach incorporates both micro- and macroevolutionary
      considerations, yet its computational requirements are modest in practice because
      the two-phase approach constrains the search space. Our hybrid algorithm can also
      be used to resolve nonbinary nodes in a multifurcating gene tree. We have
      implemented these algorithms in a software tool, NOTUNG 2.0, that can be used as
      a unified framework for gene tree reconstruction or as an exploratory analysis
      tool that can be applied post hoc to any rooted tree with bootstrap values. The
      NOTUNG 2.0 graphical user interface can be used to visualize alternate
      duplication/loss histories, root trees according to duplication and loss
      parsimony, manipulate and annotate gene trees, and estimate gene duplication
      times. It also offers a command line option that enables high-throughput analysis
      of a large number of trees.

PMID- 16597244
TI  - The average common substring approach to phylogenomic reconstruction.
AB  - We describe a novel method for efficient reconstruction of phylogenetic trees,
      based on sequences of whole genomes or proteomes, whose lengths may greatly vary.
      The core of our method is a new measure of pairwise distances between sequences.
      This measure is based on computing the average lengths of maximum common
      substrings, which is intrinsically related to information theoretic tools
      (Kullback-Leibler relative entropy). We present an algorithm for efficiently
      computing these distances. In principle, the distance of two l long sequences can
      be calculated in O(l) time. We implemented the algorithm using suffix arrays our
      implementation is fast enough to enable the construction of the proteome
      phylogenomic tree for hundreds of species and the genome phylogenomic forest for
      almost two thousand viruses. An initial analysis of the results exhibits a
      remarkable agreement with "acceptable phylogenetic and taxonomic truth." To
      assess our approach, our results were compared to the traditional (single-gene or
      protein-based) maximum likelihood method. The obtained trees were compared to
      implementations of a number of alternative approaches, including two that were
      previously published in the literature, and to the published results of a third
      approach. Comparing their outcome and running time to ours, using a "traditional"
      trees and a standard tree comparison method, our algorithm improved upon the
      "competition" by a substantial margin. The simplicity and speed of our method
      allows for a whole genome analysis with the greatest scope attempted so far. We
      describe here five different applications of the method, which not only show the
      validity of the method, but also suggest a number of novel phylogenetic insights.

PMID- 16597245
TI  - Graph theoretical insights into evolution of multidomain proteins.
AB  - We study properties of multidomain proteins from a graph theoretical perspective.
      In particular, we demonstrate connections between properties of the domain
      overlap graph and certain variants of Dollo parsimony models. We apply our graph
      theoretical results to address several interrelated questions: do proteins
      acquire new domains infrequently, or often enough that the same combinations of
      domains will be created repeatedly through independent events? Once domain
      architectures are created do they persist? In other words, is the existence of
      ancestral proteins with domain compositions not observed in contemporary proteins
      unlikely? Our experimental results indicate that independent merges of domain
      pairs are not uncommon in large superfamilies.

PMID- 16597246
TI  - De novo analysis of peptide tandem mass spectra by spectral graph partitioning.
AB  - We report on a new de novo peptide sequencing algorithm that uses spectral graph
      partitioning. In this approach, relationships between m/z peaks are represented
      by attractive and repulsive springs, and the vibrational modes of the spring
      system are used to infer information about the peaks (such as "likely b-ion" or
      "likely y-ion"). We demonstrate the effectiveness of this approach by comparison
      with other de novo sequencers on test sets of ion-trap and QTOF spectra,
      including spectra of mixtures of peptides. On all datasets, we outperform the
      other sequencers. Along with spectral graph theory techniques, the new de novo
      sequencer EigenMS incorporates another improvement of independent interest:
      robust statistical methods for recalibration of time-of-flight mass measurements.
      Robust recalibration greatly outperforms simple least-squares recalibration,
      achieving about three times the accuracy for one QTOF dataset.

PMID- 16597247
TI  - Using multiple alignments to improve gene prediction.
AB  - The multiple species de novo gene prediction problem can be stated as follows:
      given an alignment of genomic sequences from two or more organisms, predict the
      location and structure of all protein-coding genes in one or more of the
      sequences. Here, we present a new system, N-SCAN (a.k.a. TWINSCAN 3.0), for
      addressing this problem. N-SCAN can model the phylogenetic relationships between
      the aligned genome sequences, context dependent substitution rates, and
      insertions and deletions. An implementation of N-SCAN was created and used to
      generate predictions for the entire human genome and the genome of the fruit fly
      Drosophila melanogaster. Analyses of the predictions reveal that N-SCAN's
      accuracy in both human and fly exceeds that of all previously published whole
      genome de novo gene predictors.

PMID- 16597248
TI  - Protein fold recognition using segmentation conditional random fields (SCRFs).
AB  - Protein fold recognition is an important step towards understanding protein three
      dimensional structures and their functions. A conditional graphical model, i.e.,
      segmentation conditional random fields (SCRFs), is proposed as an effective
      solution to this problem. In contrast to traditional graphical models, such as
      the hidden Markov model (HMM), SCRFs follow a discriminative approach. Therefore,
      it is flexible to include any features in the model, such as overlapping or long
      range interaction features over the whole sequence. The model also employs a
      convex optimization function, which results in globally optimal solutions to the
      model parameters. On the other hand, the segmentation setting in SCRFs makes
      their graphical structures intuitively similar to the protein 3-D structures and
      more importantly provides a framework to model the long-range interactions
      between secondary structures directly. Our model is applied to predict the
      parallel beta-helix fold, an important fold in bacterial pathogenesis and
      carbohydrate binding/cleavage. The cross-family validation shows that SCRFs not
      only can score all known beta-helices higher than non-beta-helices in the Protein
      Data Bank (PDB), but also accurately locates rungs in known beta-helix proteins.
      Our method outperforms BetaWrap, a state-of-the-art algorithm for predicting beta
      helix folds, and HMMER, a general motif detection algorithm based on HMM, and has
      the additional advantage of general application to other protein folds. Applying
      our prediction model to the Uniprot Database, we identify previously unknown
      potential beta-helices.

PMID- 16597249
TI  - The multiple common point set problem and its application to molecule binding
      pattern detection.
AB  - Recognition of binding patterns common to a set of protein structures is
      important for recognition of function, prediction of binding, and drug design. We
      consider protein binding sites represented by a set of 3D points with assigned
      physico-chemical and geometrical properties important for protein-ligand
      interactions. We formulate the multiple binding site alignment problem as
      detection of the largest common set of such 3D points. We discuss the
      computational problem of multiple common point set detection and, particularly,
      the matching problem in K-partite-epsilon graphs, where K partitions are
      associated with K structures and edges are defined between epsilon-close points.
      We show that the K-partite-epsilon matching problem is NP-hard in the Euclidean
      space with dimension larger than one. Consequently, we show that the largest
      common point set problem between three point sets is NP-hard. On the practical
      side, we present a novel computational method, MultiBind, for recognition of
      binding patterns common to a set of protein structures. It performs a multiple
      alignment between protein binding sites in the absence of overall sequence, fold,
      or binding partner similarity. Despite the NP-hardness results, in our
      applications, we practically overcome the exponential number of multiple
      alignment combinations by applying an efficient branchand- bound filtering
      procedure. We show applications of MultiBind to several biological targets. The
      method recognizes patterns which are responsible for binding small molecules,
      such as estradiol, ATP/ANP, and transition state analogues.

PMID- 16597250
TI  - A practical approach to significance assessment in alignment with gaps.
AB  - Current numerical methods for assessing the statistical significance of local
      alignments with gaps are time consuming. Analytical solutions thus far have been
      limited to specific cases. Here, we present a new line of attack to the problem
      of statistical significance assessment. We combine this new approach with known
      properties of the dynamics of the global alignment algorithm and high performance
      numerical techniques and present a novel method for assessing significance of
      gaps within practical time scales. The results and performance of these new
      methods test very well against tried methods with drastically less effort.

PMID- 16597251
TI  - Alignment of optical maps.
AB  - We introduce a new scoring method for calculation of alignments of optical maps.
      Missing cuts, false cuts, and sizing errors present in optical maps are addressed
      by our alignment score through calculation of corresponding likelihoods. The size
      error model is derived through the application of Central Limit Theorem and
      validated by residual plots collected from real data. Missing cuts and false cuts
      are modeled as Bernoulli and Poisson events, respectively, as suggested by
      previous studies. Likelihoods are used to derive an alignment score through
      calculation of likelihood ratios for a certain hypothesis test. This allows us to
      achieve maximal descriminative power for the alignment score. Our scoring method
      is naturally embedded within a well known DP framework for finding optimal
      alignments.

PMID- 16597252
TI  - Modeling the combinatorial functions of multiple transcription factors.
AB  - A considerable fraction of gene promoters are bound by multiple transcription
      factors. It is therefore important to understand how such factors interact in
      regulating the genes. In this paper, we propose a computational method to
      identify groups of co-regulated genes and the corresponding regulatory programs
      of multiple transcription factors from protein- DNA binding and gene expression
      data. The key concept is to characterize a regulatory program in terms of two
      properties of individual transcription factors: the function of a regulator as an
      activator or a repressor, and its direction of effectiveness as necessary or
      sufficient. We apply a greedy algorithm to find the regulatory models which best
      explain the available data. Empirical analysis indicates that the inferred
      regulatory models agree with known combinatorial interactions between regulators
      and are robust against various parameter choices.

PMID- 16597253
TI  - HAPLOFREQ--estimating haplotype frequencies efficiently.
AB  - A commonly used tool in disease association studies is the search for
      discrepancies between the haplotype distribution in the case and control
      populations. In order to find this discrepancy, the haplotypes frequency in each
      of the populations is estimated from the genotypes. We present a new method
      HAPLOFREQ to estimate haplotype frequencies over a short genomic region given the
      genotypes or haplotypes with missing data or sequencing errors. Our approach
      incorporates a maximum likelihood model based on a simple random generative model
      which assumes that the genotypes are independently sampled from the population.
      We first show that if the phased haplotypes are given, possibly with missing
      data, we can estimate the frequency of the haplotypes in the population by
      finding the global optimum of the likelihood function in polynomial time. If the
      haplotypes are not phased, finding the maximum value of the likelihood function
      is NP-hard. In this case, we define an alternative likelihood function which can
      be thought of as a relaxed likelihood function. We show that the maximum relaxed
      likelihood can be found in polynomial time and that the optimal solution of the
      relaxed likelihood approaches asymptotically to the haplotype frequencies in the
      population. In contrast to previous approaches, our algorithms are guaranteed to
      converge in polynomial time to a global maximum of the different likelihood
      functions. We compared the performance of our algorithm to the widely used
      program PHASE, and we found that our estimates are at least 10% more accurate
      than PHASE and about ten times faster than PHASE. Our techniques involve new
      algorithms in convex optimization. These algorithms may be of independent
      interest. Particularly, they may be helpful in other maximum likelihood problems
      arising from survey sampling.

PMID- 16597254
TI  - Inference about recombination from haplotype data: lower bounds and recombination
      hotspots.
AB  - Recombination is an important evolutionary mechanism responsible for creating the
      patterns of haplotype variation observable in human populations. Recently, there
      has been extensive research on understanding the fine-scale variation in
      recombination across the human genome using DNA polymorphism data. Historical
      recombination events leave signature patterns in haplotype data. A nonparametric
      approach for estimating the number of historical recombination events is to
      compute the minimum number of recombination events in the history of a set of
      haplotypes. In this paper, we provide new and improved methods for computing
      lower bounds on the minimum number of recombination events. These methods are
      shown to detect a higher number of recombination events for a haplotype dataset
      from a region in the lipoprotein lipase gene than previous lower bounds. We apply
      our methods to two datasets for which recombination hotspots have been
      experimentally determined and demonstrate a high density of detectable
      recombination events in the regions annotated as recombination hotspots. The
      programs implementing the methods in this paper are available at
      www.cs.ucsd.edu/users/vibansal/RecBounds/.

PMID- 16597255
TI  - A linear-time algorithm for the perfect phylogeny haplotyping (PPH) problem.
AB  - Since the introduction of the Perfect Phylogeny Haplotyping (PPH) Problem in
      RECOMB 2002 (Gusfield, 2002), the problem of finding a linear-time
      (deterministic, worst-case) solution for it has remained open, despite broad
      interest in the PPH problem and a series of papers on various aspects of it. In
      this paper, we solve the open problem, giving a practical, deterministic linear
      time algorithm based on a simple data structure and simple operations on it. The
      method is straightforward to program and has been fully implemented. Simulations
      show that it is much faster in practice than prior nonlinear methods. The value
      of a linear-time solution to the PPH problem is partly conceptual and partly for
      use in the inner loop of algorithms for more complex problems, where the PPH
      problem must be solved repeatedly.

PMID- 16597256
TI  - Stability of rearrangement measures in the comparison of genome sequences.
AB  - We present data-analytic and statistical tools for studying rates of
      rearrangement of whole genomes and to assess the stability of these methods with
      changes in the level of resolution of the genomic data. We construct datasets on
      the numbers of conserved syntenies and conserved segments shared by pairs of
      animal genomes at different levels of resolution. We fit these data to an
      evolutionary tree and find the rates of rearrangement on various evolutionary
      lineages. We document the lack of clocklike behavior of rearrangement processes,
      the independence of translocation and inversion rates, and the level of
      resolution beyond which translocations rates are lost in noise due to other
      processes.

PMID- 16597257
TI  - On sorting by translocations.
AB  - The study of genome rearrangements is an important tool in comparative genomics.
      This paper revisits the problem of sorting a multichromosomal genome by
      translocations, i.e., exchanges of chromosome ends. We give an elementary proof
      of the formula for computing the translocation distance in linear time, and we
      give a new algorithm for sorting by translocations, correcting an error in a
      previous algorithm by Hannenhalli.

PMID- 16597258
TI  - Has renal-dose dopamine finally been relegated to join the long list of medical
      myths?

PMID- 16597259
TI  - Albumin use declining in UK intensive care.

PMID- 16597260
TI  - Futility--beyond a definition.

PMID- 16597261
TI  - Future requirements for quality assurance, assessment and reporting in
      Australasian ICUs.

PMID- 16597262
TI  - Imaging and the intensivist.

PMID- 16597263
TI  - Observer error and prediction of outcome--grading of head injury based on
      computerised tomography.
AB  - OBJECTIVE: To measure inter-observer error of a recently reported computerised
      tomography scoring system and to assess the ability of the scoring system to
      predict outcome in head injury patients. METHODS: Two radiologists independently
      graded all CT scans performed during the admission of all head injured patients.
      They were blinded to the clinical condition of the patient. Patients were
      followed up at 12 months and given a Glasgow outcome score. Outcomes were matched
      to the 2 independent assessments done on the first CT scan for each patient.
      RESULTS: A total of 123 head injury patients were studied. For the diffuse injury
      categories, there were 410 gradings made. Of these, 32% differed by at least one
      category. Where at least one of the radiologists identified non-evacuated mass
      lesions there were 148 gradings. Of these, one radiologist reported an un
      evacuated mass lesion in 47%, which was not reported by the other. The first CT
      scan was evaluated on 119 patients. Using the Chi-Squared test, the diffuse
      injury IV category was the only one to show a strong relationship with outcome as
      measured by the Glasgow outcome score. CONCLUSIONS: The prediction of outcome for
      head injury patients based on CT scans has significant shortcomings. In our
      study, there was significant variation in grading by experienced radiologists.
      The separate categories were also poor predictors of outcome at 12 months except
      for diffuse injury IV. The classification of mass lesions needs modification to
      be useful.

PMID- 16597264
TI  - Use of albumin in intensive care units in the United kingdom.
AB  - OBJECTIVE: To review the use of intravenous albumin solutions in intensive care
      units in the United Kingdom. METHODS: A postal questionnaire was sent to the
      clinical directors of all intensive care units in the United Kingdom (n = 292)
      asking about their use and indications for intravenous albumin solutions.
      RESULTS: Responses were received from 261 (89.4%) intensive care units (ICUs).
      The units were classified as general ICUs (n = 198), paediatric ICUs (n = 22) and
      combined intensive care/coronary care units (ICU/CCUs) (n = 41). Of the 261 units
      that replied, 181 (69.3%) reported using intravenous albumin, although the
      indications varied between units particularly in paediatric intensive care units.
      The alternatives to albumin also varied between the units. The general ICUs
      favoured hydroxyethyl starch (n = 129, 65.2%) and/or gelatin solutions (n = 87,
      43.9%), as did the combined ICU/CCUs (n = 28, 68.3% and/or n = 23, 56.1%
      respectively). However, of the paediatric ICUs that used an alternative to
      albumin solutions (n = 21/22), 12 favoured crystalloid solutions (54.5%) and 9
      favoured gelatin solutions (40.9%). We also assessed the impact of the recent
      review by the Cochrane Injuries Group Reviewers on the use of albumin and found
      that the respondents of 131 units (50.2%) reported that this study influenced
      their use of intravenous albumin. Of the 80 units that did not use albumin
      solutions, 33 units reported that they had ceased using intravenous albumin
      following the review from the Cochrane Injuries Group Reviewers. CONCLUSIONS:
      Approximately two-thirds of intensive care units in the United kingdom reported
      using intravenous albumin, although the indications varied between units. In many
      of these units the use of intravenous albumin had been influenced by the recent
      review by the Cochrane Injuries Group Reviewers on the use of albumin.

PMID- 16597265
TI  - Antiarrhythmic and haemodynamic effects of the commonly used intravenous
      electrolytes.
AB  - OBJECTIVE: To review the physiology and cardiovascular effects of the commonly
      used intravenous electrolytes. DATA SOURCES: Abstracts, articles and published
      reviews of studies reported from 1966 to 2000 and identified through a MEDLINE
      search on cardiac arrhythmias and electrolytes. SUMMARY OF REVIEW: While isotonic
      saline solutions are used to improve the haemodynamic status in critically ill
      patients who are hypotensive and hypovolaemic, other intravenous solutions
      including potassium chloride, calcium chloride, magnesium sulphate and sodium or
      potassium phosphate as well as hypertonic saline and sodium bicabonate have
      unique and often therapeutically useful haemodynamic and antiarrhythmic effects.
      Potassium chloride solutions are used to treat hypokalaemia with a maximum speed
      of correction in an adult of 20 mmol per 30 minutes when an acute myocardial
      infarct is present. A greater infusion rate may be necessary when ventricular or
      supraventricular tachyarrhythmias are present although close ECG monitoring will
      be required. Magnesium sulphate (2-20 mmol) has been used for hypomagnesaemic and
      normomagnesaemic cardiac arrhythmias (particularly when digoxin induced) and
      calcium chloride (3.4-6.8 mmol) is used to treat hyperkalaemic and
      hypermagnesaemic cardiac arrhythmias. Both hypertonic sodium bicarbonate and
      sodium chloride solutions have antiarrhythmic effects that may be beneficial in
      conditions that include tricyclic poisoning, hyperkalaemia and bupivicaine
      toxicity, although sodium bicarbonate is generally used for tricyclic
      cardiotoxicity. Low cardiac output states and arrhythmias have also been reported
      in hypophosphataemic patients that are reversed by infusions of potassium or
      sodium phosphate. CONCLUSIONS: Intravenous potassium chloride, calcium chloride,
      magnesium sulphate, sodium and potassium phosphate, sodium bicarbonate and
      hypertonic saline can be used effectively to alter the haemodynamic status and
      manage cardiac arrhythmias. However, their indications are selective and
      complications may occur, so careful administration and monitoring are required
      with their use.

PMID- 16597266
TI  - Basic head CT for intensivists.
AB  - OBJECTIVE: To present a simplified approach to computed tomography (CT) of the
      head to facilitate the understanding and diagnosis of common acute cerebral
      abnormalities in the critically ill patient. DATA SOURCES: Published articles and
      texts on cerebral disorders and CT diagnosis. SUMMARY OF REVIEW: In the
      unconscious and acutely ill patient a head CT is often performed to assess the
      possibility of an organic or 'space occupying' cerebral lesion. While specialist
      radiological interpretation is often available during the day, when an 'out of
      hours' emergency occurs the diagnosis of an intracerebral abnormality often
      relies upon the intensivist's interpretation of the head CT scan. With an
      understanding of the position and appearance of normal intracerebral structures
      (and artifacts) common acute cerebral disorders can be easily assessed by the non
      radiologist, facilitating the correct diagnosis and the appropriate management.
      CONCLUSIONS: Head CT is the commonest CT performed in the intensive care unit. In
      many patients who are sedated or ventilated, neurological examination is
      sometimes difficult and CT becomes important in clarifying patient's neurological
      status. A simple approach to the interpretation of brain CT images assists in the
      management of these cases.

PMID- 16597267
TI  - Acute myocardial ischaemia in the presence of thrombotic thrombocytopenic
      purpura: what are the treatment options?
AB  - We describe a case of severe myocardial ischaemia in the setting of thrombotic
      thrombocytopoenic purpura (TTP). In this report, we discuss the potential
      difficulties in the diagnosis and management of acute myocardial ischaemia with
      TTP, particularly relating to the use of antiplatelet agents. We also highlight
      the importance of careful monitoring during plasma exchange for TTP when acute
      myocardial ischaemia is present. The potential role for novel therapies in the
      management of TTP related myocardial ischaemia is also discussed.

PMID- 16597268
TI  - Organ donation in Australia and New Zealand--ICU perspectives.

PMID- 16597269
TI  - "But...?".

PMID- 16597270
TI  - Development of audit and quality assurance in an intensive care unit. A smaller
      hospital perspective.

PMID- 16597271
TI  - A 32 year old woman admitted to the intensive care unit with hypoxia, generalised
      weakness and agitation.

PMID- 16597272
TI  - Baclofen overdose.

PMID- 16597273
TI  - Intravenous infusions of Albuminex 4% (human albumin 4%) and hypotension.

PMID- 16597274
TI  - The pupillary light reflex in the critically ill patient.

PMID- 16597275
TI  - Haemodynamic targets in shock: choosing a pressure.

PMID- 16597276
TI  - The ANZICS clinical trials group.

PMID- 16597277
TI  - Microwave warming of fluids--pH and other questions.

PMID- 16597278
TI  - Mannitol for resuscitation in acute head injury: effects on cerebral perfusion
      and osmolality.
AB  - OBJECTIVE: To review the use of mannitol during initial resuscitation following
      traumatic brain injury and to determine the effects of mannitol on subsequent
      management following resuscitation and commencement of neuromonitoring. METHODS:
      A retrospective audit of patients presenting to a tertiary hospital with severe
      head injury (Glasgow coma score < or = 8). Patients were divided into two groups
      according to whether they received mannitol during initial resuscitation.
      Measurements included initial plasma osmolality, cerebral perfusion pressure
      (CPP), intracranial pressure (ICP) and jugular venous saturation (SjO2). RESULTS:
      Forty patients were identified: 19 received mannitol prior to admission to the
      intensive care unit. Of these, only 2 patients fulfilled acceptable neurological
      indications for mannitol. The mannitol patients received a mean dose of 237 mL of
      20% mannitol (47.4 g) and had significantly higher initial osmolalities than the
      patients who did not receive mannitol (293 vs 279 mosmol/L, p < 0.05). No
      significant difference in initial CPP, ICP, or SjO2 was identified. The mannitol
      patients were further subdivided into two 12-month periods (1994 and 1995). A
      dose related, significant difference in initial osmolalities was identified (140
      vs 344 mL and 284 vs 304 mosmol/L respectively, p < 0.05). The latter group (n =
      9) had significantly lower initial CPPs (72 vs 59 mmHg) and higher ICPs (14 vs 18
      mmHg). No difference in 6 month Glasgow outcome scores between groups was
      demonstrated. CONCLUSIONS: The empirical overuse of mannitol is common. Mannitol
      did not exert any beneficial effect on CPP, ICP or SjO2 in the initial phases of
      management. Larger doses (i.e. > 20 g) are associated with increased osmolality
      which may reduce CPP.

PMID- 16597279
TI  - The effect of microwave heating on the acidity of 0.9% saline in 1 litre and 100
      mL polyvinyl chloride packaging.
AB  - OBJECTIVE: Microwave warming of intravenous crystalloid solutions is an accepted
      practice in operating suites and emergency departments. These intravenous
      solutions are stored in polyvinyl chloride (PVC) and are known to be acidic. Some
      of this acidity may be from PVC packaging. We asked if microwave heating affected
      the acidity of 0.9% saline solution in 1 litre and 100 mL PVC bags. METHODS:
      Seven 1 litre bags were heated in an 800 Watt microwave for 2 minutes each and
      seven 100 mL bags were heated for 30 seconds each. After overnight cooling to
      room temperature, pH and temperature were measured and compared with two control
      groups of 7 unheated bags. RESULTS: There was no significant difference between
      the pH of heated and unheated solutions of saline. The median pH of the 1 litre
      bags were 5.01 (control) and 5.02 (heated). The median pH of the 100 mL bags were
      4.58 (control) and 4.59 (heated). Post hoc, we found the 100 mL bags were more
      acidic than the 1 litre bags by a median difference of 0.43 pH units (P = 0.002).
      CONCLUSIONS: Microwave heating does not change the acidity of 0.9% saline in 1
      litre or 100 mL PVC packaging.

PMID- 16597280
TI  - Induced and accidental hypothermia.
AB  - OBJECTIVE: To review human thermoregulation and the pathophysiology and
      management of induced and accidental hypothermia. DATA SOURCES: A review of
      studies reported over ten years from 1990 to 2000 and identified through a
      MEDLINE search of the English-language literature on thermoregulation and induced
      and accidental hypothermia. SUMMARY OF REVIEW: Hypothermia is defined as a core
      temperature less than 35 degrees C, and may be therapeutic (i.e. induced for
      clinical benefit) or accidental. Hypothermia induced prior to cardiovascular or
      neurosurgical procedures (i.e. therapeutic hypothermia) allows for a greater
      hypotensive operative period with less risk of cerebral or cardiac ischaemic
      injury. Hypothermia induced following tissue injury (e.g. closed head injury,
      cerebrovascular accident, adult respiratory distress syndrome) has also been used
      to reduce ischaemic tissue injury, although significant clinical benefits have
      not yet been demonstrated. Inadvertent hypothermia (i.e. accidental hypothermia)
      is classed as mild from 33 degrees C-35 degrees C, moderate from 30 degrees C-33
      degrees C and severe if less than 30 degrees C. Treatment includes surface and
      core warming methods, all of which have a valid basis from experimental studies.
      However, no prospective, randomised controlled clinical trials exist that have
      compared the various rewarming methods. Currently, passive rewarming methods
      (e.g. reflective metalloplastic sheets, blankets) are recommended for patients
      with mild hypothermia (> 33 degrees C), active surface rewarming (e.g. heated
      blankets, hot air circulators) for moderate hypothermia (> 30 degrees C), active
      core rewarming (e.g. heated haemodialysis, haemodiafiltration or peritoneal
      dialysis) for severe hypothermia (< 30 degrees C), and heated cardiopulmonary
      bypass for severe hypothermia with cardiopulmonary arrest. CONCLUSIONS: Operative
      hypothermia reduces ischaemic injury during cardiac and neurosurgical procedures.
      Hypothermia induced following tissue injury has not yet been shown to be of
      benefit. Management of accidental hypothermia requires passive and active warming
      methods, the indication of each depending on the availability of the method and
      severity of hypothermia.

PMID- 16597281
TI  - Traumatic laryngeal injury in a nine year old child--the 'padded dash' syndrome
      revisited.
AB  - A case is presented of a 9-year-old girl who sustained a traumatic injury to the
      larynx following a frontal impact motor vehicle accident. The type of injury
      sustained was typical of what is now called the 'padded dash' syndrome. On impact
      the anterior aspect of the neck strikes the car dashboard resulting in the larynx
      being crushed against the vertebral column. The victim is often unrestrained. The
      injury was detected only at extubation whereupon severe respiratory distress
      ensued. Injury to the larynx is uncommon at all ages, even more so in children.
      In the paediatric age group signs and symptoms may be minimal and a high index of
      suspicion is required. The diagnosis and management of these injuries with
      special reference to childhood is discussed.

PMID- 16597282
TI  - The differential diagnosis of fixed dilated pupils: a case report and review.
AB  - This case report describes a patient with Guillain-Barre syndrome in whom the
      presence of coma and absent brain stem reflexes suggested the possibility of
      brainstem death. A differential diagnosis of fixed dilated pupils is presented.

PMID- 16597283
TI  - Septic jugular thrombophlebitis and pulmonary embolism: a case report.
AB  - Bacterial oropharyngeal infections in healthy young people rarely give rise to
      life threatening complications. Lemierre's disease, caused by Fusobacetrium
      necrophorum, manifests as pharyngitis, jugular venous thrombosis and septic
      pulmonary embolism. A previously fit young male presenting with prolonged
      pharyngitis, complicated by severe pneumonia and septicaemia is presented.
      Recognition of this syndrome and early antibiotic therapy can prevent significant
      morbidity in otherwise healthy people.

PMID- 16597284
TI  - Cerebrospinal fluid in critical illness.
AB  - OBJECTIVE: To detail the physiology, pathophysiology and recent advances in
      diagnostic analysis of cerebrospinal fluid (CSF) in critical illness, and briefly
      review the pharmacokinetics and pharmaco-dynamics of drugs in the CSF when
      administered by the intravenous and intrathecal route. DATA SOURCES: A review of
      articles published in peer reviewed journals from 1966 to 1999 and identified
      through a MEDLINE search on the cerebrospinal fluid. SUMMARY OF REVIEW: The
      examination of the CSF has become an integral part of the assessment of the
      critically ill neurological or neurosurgical patient. Its greatest value lies in
      the evaluation of meningitis. Recent publications describe the availability of
      new laboratory tests on the CSF in addition to the conventional cell count,
      protein sugar and microbiology studies. Whilst these additional tests have
      improved our understanding of the pathophysiology of the critically ill
      neurological/neurosurgical patient, they have a limited role in providing
      diagnostic or prognostic information. The literature pertaining to the use of
      these tests is reviewed together with a description of the alterations in CSF in
      critical illness. The pharmacokinetics and pharmacodynamics of drugs in the CSF,
      when administered by the intravenous and the intrathecal route, are also
      reviewed. CONCLUSIONS: The diagnostic utility of CSF investigation in critical
      illness is currently limited to the diagnosis of an infectious process. Studies
      that have demonstrated some usefulness of CSF analysis in predicting outcome in
      critical illness have not been able to show their superiority to conventional
      clinical examination. With further advances in our understanding of neurological
      function and refinement in biochemical analysis there remains the possibility of
      useful cerebrospinal fluid diagnostic and prognostic markers in the future.

PMID- 16597285
TI  - Shock: a review of pathophysiology and management. Part I.
AB  - OBJECTIVE: To review pathophysiology and management of hypovolaemic, cardiogenic
      and septic shock in a two-part presentation. DATA SOURCES: Articles and published
      peer-review abstracts and a review of studies reported from 1994 to 1998 and
      identified through a MEDLINE search of the English language literature on septic
      shock, cardiogenic shock and hypovolaemic shock. SUMMARY OF REVIEW: Shock is a
      clinical syndrome characterised by hypotension (i.e. a systolic blood pressure
      less than 90 mmHg or a mean arterial pressure less than 60 mmHg or reduced by
      greater than 30%, for at least 30 minutes), oliguria (i.e. a urine output less
      than 20 mL/hr or 0.3 ml/kg/hr for 2 consecutive hours), and poor peripheral
      perfusion (e.g. cool and clammy skin which demonstrates poor capillary refill).
      Hypovolaemic and cardiogenic shock are associated with disorders that cause an
      under-lying haemodynamic defect of a low intravascular volume and a reduction in
      myocardial contractility, respectively. The understanding and management of
      hypovolaemic shock has changed very little over the past 50 years with treatment
      requiring management of the causative lesion (i.e. surgical correction of blood
      loss) and replacement of the intravascular volume by infusing blood and/or 0.9%
      sodium containing colloid or crystalloid fluids. Due to recent developments in
      percutaneous coronary revascularisation techniques, management of cardiogenic
      shock in some centers has changed. Emergency cardiac catheterisation with urgent
      myocardial reperfusion (using percutaneous transluminal coronary angioplasty or
      coronary artery stenting in selected cases) and use of glycoprotein IIb/IIIa
      antagonists while supporting the circulation using an intra-aortic Balloon pump,
      has been reported to reduce mortality of cardiogenic shock in acute myocardial
      infarction. Large randomised, controlled multicentre trials are awaited.
      CONCLUSIONS: Hypovolaemic shock requires urgent management of the underlying
      defect and replacement of the intravascular volume loss. Recent studies in
      management of cardiogenic shock using urgent revascularisation and intra-aortic
      Balloon counterpulsation in patients with acute myocardial infarction have shown
      a reduction in mortality in selected cases.

PMID- 16597286
TI  - Shock: a review of pathophysiology and management. Part II.
AB  - OBJECTIVE: To review pathophysiology and management of hypovolaemic, cardiogenic
      and septic shock in a two part presentation. DATA SOURCES: Articles and published
      peer-review abstracts and a review of studies reported from 1994 to 1998 and
      identified through a MEDLINE search of the English language literature on septic
      shock, cardiogenic shock and hypovolaemic shock. SUMMARY OF REVIEW: The
      pathophysiological effects of cardiogenic and hypovolaemic shock are related
      predominantly to a reduction in preload and myocardial contractility,
      respectively, whereas the pathophysiological effects of septic shock result
      largely from the overwhelming production of inflammatory mediators. The excessive
      inflammatory response results in haemodynamic compromise and widespread tissue
      injury. While the understanding of the acute inflammatory reaction has improved,
      therapies to modulate the chemical mediators responsible for the organ
      dysfunction associated with this reaction have not altered mortality, and in some
      instances may have increased it. Treatment of septic shock is still largely
      supportive, using intravenous fluids and inotropic agents to provide adequate
      tissue perfusion while the infective lesion is managed with antibiotic therapy
      and surgical drainage of septic focus. CONCLUSIONS: Septic shock is provoked by
      an excessive acute inflammatory response to an infection. Management of the shock
      is supportive using fluids and inotropic agents, while antibiotic therapy and
      surgical drainage of the septic focus take effect. Immunomodulation of the acute
      inflammatory response causing septic shock has not improved mortality.

PMID- 16597287
TI  - Crystalloids, colloids, or blood.

PMID- 16597288
TI  - Could we have a second opinion?

PMID- 16597290
TI  - Delayed dissection of the internal carotid artery following major facial trauma.

PMID- 16597289
TI  - Emergency management of seizures.

PMID- 16597291
TI  - Where the Birds still rule.

PMID- 16597292
TI  - Pulmonary artery catheter versus new technology.

PMID- 16597294
TI  - Defending cerebral perfusion pressure in traumatic brain injury: the goalposts
      keep moving.

PMID- 16597293
TI  - Does oxygen debt play a central or peripheral role (or any role) in the
      pathophysiology of septic shock?

PMID- 16597295
TI  - 'Spot diagnosis' in the ICU patient.

PMID- 16597296
TI  - The epidemiology of major early adverse physiological events after surgery.
AB  - OBJECTIVE: To study the incidence of major post-operative adverse physiological
      events in a tertiary hospital. METHODS: Non-cardiac, surgical in-patients were
      studied for the first three post-operative days. Daily assessment was by patient
      visit, chart review and laboratory result analysis. Pre-determined diagnostic
      criteria for the identification of adverse physiological events were used.
      RESULTS: One hundred and seven patients were studied. The mean age was 61 +/- 20
      years. Forty-four were female and 63 were male. Pre-operatively, 48 patients had
      one or more of 34 different co-morbidities. Forty three (40%) of the 107 patients
      had one or more major adverse physiological events. These events included
      hypotension 24 (22%), altered mental state 16 (15%), oliguria 9 (8.4%), abnormal
      heart rate 8 (7.5%) and abnormal respiratory rate 5 (4.7%). Morbidity associated
      with these events included respiratory failure 5 (4.7%), prolonged altered mental
      state 5, (4.7%), and septic shock 3 (2.8%). There were two deaths. Adverse
      physiological events were common in thoracic 5/9 (56%), neurosurgical 4/10 (40%)
      and vascular 8/13 (62%) patients. Prolonged altered mental state was most common
      among orthopaedic patients 5/22 (23%). Adverse physiological events were more
      frequent in the elderly than the young: 14/52 (27%) in those who were less than
      65 years of age versus 29/55 (53%) in those who were 65 years and older (p <
      0.025). There was a non-significant increase (p < 0.1) in adverse physiological
      events in patients having emergency surgery 16/28 (57%) compared with those
      having elective surgery 27/79 (34%). CONCLUSIONS: This study reveals a high
      incidence of post-operative adverse physiological events in surgical patients in
      a university teaching hospital and identifies several high-risk groups. Further
      studies are needed to define the clinical significance of these events,
      appropriate management and prognosis.

PMID- 16597297
TI  - Early diagnosis of traumatic aortic valve rupture in ICU patients using
      transoesophageal echocardiography.
AB  - A case is presented of a 60-year-old man who sustained spinal and chest wall
      injuries following a collision between his glider and an aeroplane. The severity
      of his injuries required him to be managed with bilateral underwater seal drains,
      cervical spine stabilisation and sedation with mechanical ventilation. Due to the
      severity of his chest trauma, a transoesophageal echocardiograph was performed
      which revealed a partial dehiscence and prolapse of the left coronary cusp of the
      aortic valve with mild to moderate aortic regurgitation. Despite conservative
      treatment, severe cardiac failure developed six days later requiring aortic valve
      replacement. After a prolonged stay in the Intensive Care Unit during which the
      patient developed acute respiratory distress syndrome, methicillin resistant
      Staphylococcus aureus pneumonia and Enterobacter septicaemia, the patient was
      discharged, returning to his pre-admission lifestyle. In patients with complex
      and severe chest trauma, transoesophageal echocardiography is of great benefit,
      not only in allowing good image quality, compared with transthoracic
      echocardiography, but having a greater reliability and accuracy in diagnosing
      cardiac and mediastinal trauma in complex monitoring environments.

PMID- 16597298
TI  - Diseases of the aorta in the critically ill.
AB  - OBJECTIVE: To review diseases of the aorta that commonly require management in
      the critical care unit. DATA SOURCES: Articles and published reviews on aortic
      dissection, traumatic aortic rupture and aortic aneurysm. SUMMARY OF REVIEW: The
      aorta is the largest arterial vessel of the body and disorders that can lead to
      rupture (e.g. aortic dissection, traumatic aortic rupture and aortic aneurysm)
      are life threatening. Aortic dissections are usually classified for surgical
      purposes as those that involve the ascending aorta (i.e. type A dissections)
      which are usually managed surgically and all other dissections (i.e. type B
      dissections) which are usually managed non surgically. Recently, endoluminal
      aortic stents have been used to manage type B dissections. Traumatic aortic
      rupture usually follows an antero-posterior thoracic injury with 60% occurring
      just distal to the origin of the left subclavian artery and 25% at the ascending
      aorta. Treatment consists of open surgical repair ensuring that the aortic cross
      clamp times are less than 30 minutes to reduce the development of ischaemic cord
      lesions. Aortic aneurysm commonly occurs in the abdominal aorta and is usually
      surgically resected if > 5 cm in diameter. Post-operative care is commonly
      undertaken in the intensive care unit to monitor haemodynamic, respiratory and
      fluid and electrolyte status to reduce the incidence of renal and respiratory
      failure. While angiography is often used to diagnose these disorders,
      transoesophageal echocardiography, helical computed tomography (CT) and magnetic
      resonance imaging are becoming more commonly used and in selected conditions are
      recommended as the investigations of choice. CONCLUSIONS: Aortic dissection,
      aortic aneurysm and aortic trauma may lead to aortic rupture with exsanguination
      and management commonly requires surgical intervention and postoperative care in
      a critical care unit.

PMID- 16597299
TI  - Acute ischaemic stroke: part I. The carotid circulation.
AB  - OBJECTIVE: To review recent advances in the management of acute ischaemic stroke
      in a two part presentation. DATA SOURCES: Articles and a review of studies
      reported from 1990 to 2000 and identified through a MEDLINE search of the English
      language literature on acute ischaemic stroke. SUMMARY OF REVIEW: An acute
      ischaemic stroke is characterised clinically by the rapid development of a
      neurological deficit caused by a thrombus or embolus in the carotid (i.e.
      anterior) circulation or vertebrobasilar (i.e. posterior) circulation. Management
      requires urgent computed tomography to differentiate it from a haemorrhagic
      stroke. Ancillary investigations of echocardiography and thrombophilia screen may
      also be required if a cardiac embolic condition or hypercoagulable state is
      suspected, respectively. Cerebral magnetic resonance imaging, angiography and
      duplex ultrasonography with Doppler analysis of cerebral blood flow are becoming
      increasingly useful in determining the site and extent of the ischaemic lesion.
      Lumbar puncture is rarely required. Treatment with aspirin (150-300 mg) within
      the first 48 hr as well as management in a specialised unit focusing on
      resuscitation and prevention of complications (e.g. maintaining hydration and
      nutrition, and preventing aspiration and pressure sores, etc), has reduced
      morbidity and mortality associated with acute ischaemic strokes. However, while
      therapy to improve cerebral blood flow using thrombolytics, anticoagulants,
      glycoprotein IIb/IIIa inhibitors or fibrinogen depleting agents or
      neuroprotective agents to reduce further neuronal damage (e.g. solfotel,
      eliprodil, lubeluzole) have shown promise experimentally and in specific clinical
      circumstances, they have not produced consistent improvement in morbidity or
      mortality. CONCLUSIONS: An acute ischaemic stroke in the distribution of the
      carotid circulation requires aspirin 150-300 mg daily and management in an acute
      stroke unit. Thrombolytic therapy (with rt-PA within the first three hours) to
      improve cerebral blood flow has limited application, and current neuroprotective
      agents have not yet been shown to be of benefit.

PMID- 16597300
TI  - Acute ischaemic stroke: part II. The vertebrobasilar circulation.
AB  - OBJECTIVE: To review recent advances in the management of acute ischaemic stroke
      in a two part presentation. DATA SOURCES: Articles and a review of studies
      reported from 1990 to 2000 and identified through a MEDLINE search of the English
      language literature on acute ischaemic stroke. SUMMARY OF REVIEW: An acute
      ischaemic stroke of the vertebrobasilar circulation is investigated initially
      with a cerebral computed tomography scan largely to differentiate it from a
      haemorrhagic stroke. However, cerebral magnetic resonance imaging identifies the
      ischaemic brainstem lesions more accurately and is often performed with MR
      angiography to determine the site and extent of the ischaemic vertebrobasilar
      lesion. Treatment with aspirin (150-300 mg) within the first 48 hr as well as
      management in a specialised unit focusing on resuscitation and prevention of
      complications has reduced morbidity and mortality. While therapy to improve
      cerebral blood flow or agents to reduce further neuronal damage have not produced
      consistent improvement in outcome, numerous small studies using intravenous or
      intraarterial thrombolytics, percutaneous transluminal angioplasty or stents have
      reported improved outcome in selected cases. CONCLUSIONS: An acute ischaemic
      stroke in the distribution of the vertebrobasilar circulation requires aspirin
      150-300 mg daily and management in an acute stroke unit. Intra-arterial or
      intravenous thrombolytic therapy and percutaneous transluminal angioplasty or
      stents to improve cerebral blood flow (even up to 24 hours after the event) have
      been reported to be beneficial in selected cases.

PMID- 16597302
TI  - High risk non-cardiac surgery--is supranormal oxygen delivery the answer.

PMID- 16597301
TI  - Pulmonary artery catheterisation--a problem swept under the carpet?

PMID- 16597303
TI  - A 38 year old man admitted to accident and emergency, confused and agitated.

PMID- 16597304
TI  - Futility, right to die, withdrawal of therapy and the ICU as a medical purgatory.

PMID- 16597306
TI  - Why do we continually ask "Do we need intensivists"?

PMID- 16597305
TI  - Mis-diagnosis of brown snake bite?

PMID- 16597307
TI  - Quantifying and improving functional survival in traumatic brain injury.

PMID- 16597308
TI  - How should we measure the emotional well-being of paediatric intensive care
      patients?

PMID- 16597309
TI  - Relative risks: relative benefits.

PMID- 16597310
TI  - Cognitive and psychosocial outcome in survivors of severe traumatic brain injury:
      correlations with cerebral perfusion pressure, frontal lobe damage and
      somatosensory evoked potentials.
AB  - OBJECTIVE: To correlate neuropsychological outcome in patients after severe
      traumatic head injury, with neurophysiological and neuroradiological data
      collected during the intensive care unit (ICU) period of care. METHODS: Patients
      admitted to Waikato Hospital ICU with severe traumatic head injury were studied.
      Respiratory difficulty at the accident site, admission Glasgow Coma Score (GCS),
      anatomic traumatic brain disruption as quantified by a cerebral computed
      tomography score, prolongation of the central conduction time (CCT) of
      somatosensory evoked potentials and the percentage time that the cerebral
      perfusion pressure was less than 70 mmHg (%CPP < 70) were measured.
      Neuropsychological outcome was assessed, in terms of cognitive and behavioural
      function, by the Controlled Oral Word Association (COWA) test (performed by the
      patient) and Head Injury Behaviour rating scale (HIBS, performed by their
      caregiver) respectively, one year following injury. RESULTS: Sixty-eight patients
      with a median post-resuscitation GCS of 6 were able to complete the
      neuropsychological follow up. Most patients had significantly impaired cognitive
      and behavioural function (mean COWA = 32 and HIBS = 9.7). Cognitive function did
      not correlate significantly with behavioural function (COWA vs HIBS, r = -0.14, p
      = 0.27). There were no significant correlations between either GCS (r = 0.15, p =
      0.28) or estimates of respiratory difficulty at the accident scene and
      neuropsychological outcome. Poor cognitive outcome (COWA) was correlated with
      %CPP < 70 (r =-0.41, p = 0.005) and prolonged CCT (r = 0.26, p = 0.03). There was
      an insignificant correlation between the CT score and cognitive outcome (frontal
      lobe score vs COWA, r = -0.12, p = 0.33). However, the group of patients with the
      most severe frontal lobe injury tended to have a worse behavioural outcome as
      assessed by the HIBS. CONCLUSIONS: Behavioural outcome as quantified by the
      caregiver (HIBS) does not correlate well with the degree of cognitive impairment
      as measured directly from the patient (COWA). Severely head injured patients with
      poor neurophysiological indicators (%CPP < 70 or prolonged CCT) have a poor
      neuropsychological outcome. However, anatomical disruption of the brain as
      estimated by the frontal lobe CT score correlated poorly with outcome.

PMID- 16597311
TI  - Can children recall their experiences of admission to an intensive care unit?
AB  - OBJECTIVE: To perform a pilot study to prospectively determine children's ability
      to recall events experienced during admission to a paediatric intensive care
      unit. METHODS: Children's recall of the intensive care experience was evaluated,
      using telephone interview, at four to eight weeks and six to twelve months
      following discharge. Separate scores were assigned to reflect children's recall
      of general events and painful events. Recall was classified as either limited or
      extensive. Statistical analysis was performed to detect change in recall status
      over time and the association between the ability to recall and relevant
      admission variables (previous admission status, type of admission,
      frequency/intensity of painful procedures, length of stay and administration of
      analgesia/sedation). RESULTS: In a sample of 50 children, recall of general
      events was extensive 4-8 weeks after discharge in 29 (58%) children and extensive
      in 26 (52%) children 6-12 months after discharge. Recall of painful events was
      extensive 4-8 weeks after discharge in 15 (30%) children and 14 (28%) children at
      6-12 months after discharge. Thirteen (33.3%) of the 39 children who received
      analgesia/sedation had extensive recall of painful events at 4-8 weeks after
      discharge; 12 (30.8%) children had extensive recall at 6-12 months after
      discharge. CONCLUSIONS: Children have the ability to recall many of their
      experiences related to admission to a paediatric intensive care unit and can
      continue to recall many of these experiences twelve months after discharge.
      Despite current methods for guiding titration of opiate infusions and
      intermittent administration of benzodiazepines, many children can recall painful
      experiences and general events encountered within the intensive care unit.

PMID- 16597312
TI  - Magnesium for atrial fibrillation after coronary artery bypass graft surgery: its
      role in aetiology and prevention.
AB  - OBJECTIVE: To summarise the potential consequences of atrial fibrillation (AF)
      after coronary artery bypass graft surgery (CABG) and the relationship of the
      arrhythmia with serum magnesium concentration ([Mg]) and to review the trials of
      magnesium supplementation as prophylaxis against post-CABG AF. DATA SOURCES:
      Abstracts, articles and published reviews on AF after CABG and magnesium
      prophylaxis. SUMMARY OF REVIEW: AF after CABG occurs in 20-40% of patients. It
      may cause haemodynamic compromise, stroke, prolongation of hospital stay and an
      increased use of resources. Effective prophylaxis offers the enticing prospect of
      reductions in morbidity, hospital stay and resource utilisation. There is
      circumstantial evidence suggesting that hypomagnesaemia may predispose to cardiac
      arrhythmias. Serum [Mg] falls after CABG due to haemodilution and beta-adrenergic
      mediated mechanisms. Several studies have reported an association between
      hypomagnesaemia and post-CABG AF, but a causal relationship has not been
      established. Trials have demonstrated that magnesium (Mg) replacement can
      attenuate the perioperative fall in serum [Mg], but have failed to show efficacy
      of Mg therapy in AF prevention after CABG. The perioperative changes in serum
      [Mg] do not seem to reflect changes in intracellular magnesium, including within
      the atria. CONCLUSIONS: AF after CABG is common and a drain on resources through
      its association with increased morbidity and hospital stay. Previous studies
      investigating the relationship between serum [Mg] and AF after CABG have produced
      inconsistent results. The current evidence from randomised, placebo-controlled
      trials does not support the use of Mg therapy to prevent AF after CABG and
      strengthens the likelihood of any association between post-CABG AF and
      hypomagnesaemia being a passive one. That Mg appears ineffective as prophylaxis
      for postoperative AF may partly be due to limitations in trial methodology, but
      most probably reflects the poor correlation between serum total [Mg] and
      intracellular magnesium, specifically the intra-atrial magnesium content.

PMID- 16597313
TI  - Ventilator-induced lung injury and implications for clinical management.
AB  - OBJECTIVE: To review recent studies in pathogenesis and management of ventilator
      induced lung injury. DATA SOURCES: Articles and published reviews on ventilator
      induced lung injury, barotrauma and acute lung injury. SUMMARY OF REVIEW: This
      review summarises the important differences between clinically apparent
      'barotrauma' and the more subtle changes in lung structure and function
      associated with ventilation. Of great importance is the understanding that as the
      underlying lung injury worsens, the degree of injury from mechanical ventilation
      increases. An inflammatory process results from mechanical stimuli and this may
      contribute to distant organ dysfunction. A great deal of knowledge has been
      obtained from the use of animal models, however, one must be cautious about
      extrapolating these findings directly to the clinical setting without the use of
      adequately designed clinical trials. Tidal volume reduction and higher levels of
      PEEP and recruitment manoeuvres should be employed given the available evidence.
      The use of high frequency techniques, surfactant therapy despite their past track
      record, may prove to be exciting 're-discoveries'. CONCLUSIONS: Ventilator
      induced lung injury is an iatrogenic disturbance that increases morbidity and
      mortality associated with acute respiratory distress syndrome. Tidal volume
      reduction and increased levels of PEEP have reduced inflammatory mediators and
      the mortality associated with ARDS.

PMID- 16597314
TI  - Life threatening massive pulmonary embolism treated with reteplase: a case
      report.
AB  - We describe a case of sudden and severe pulseless electrical activity in a 30
      year old woman which was managed successfully with reteplase and heparin one day
      following an anterior cruciate ligament repair. The presentation of a sudden
      collapse with ECG findings of S1Q3T3, early precordial lead ST depression and
      partial right bundle branch block were indicative of an acute pulmonary embolus.
      The cardiopulmonary collapse necessitated rapid treatment in the absence of
      confirmatory investigations. Reteplase (10 U stat followed by 10 U at 30 minutes)
      led to a dramatic improvement in the cardiovascular status of the patient. One
      day following the cardiac arrest the patient was extubated and responding
      normally. A spiral CT performed later confirmed multiple small embolic defects in
      the lower pulmonary arteries of both lower lung zones. This case highlights the
      utility of reteplase in the management of an acute pulmonary embolism and in an
      emergency, recent surgery is not necessarily a contraindication to its use.

PMID- 16597315
TI  - Towards better ICU antibiotic dosing.
AB  - OBJECTIVE: To review the recent pharmacokinetic and pharmacodynamic reports of
      some of the commonly used antibiotics in critically ill patients and recommend
      alterations in their administration to improve their efficacy. DATA SOURCES:
      Relevant articles and published reviews on aminoglycoside, third and fourth
      generation cephalosporins, vancomycin and ciprofloxacin dosing in critically ill
      patients. SUMMARY OF REVIEW: Antibiotic regimens are derived from non-critically
      ill volunteers. To optimise antibiotic administration in the intensive care unit,
      the different 'kill-characteristics' of the antibiotic classes and the altered
      drug pharmacokinetics in critically ill patients should be considered together to
      re-evaluate the currently recommended regimens. Aminoglycosides require high peak
      levels to be most effective, hence large single daily doses are important. With
      the increased clearances in the critically ill patient, particularly those who
      have normal renal function, a more frequent administration than single daily
      dosing may be optimal (e.g. 18-hourly). Increased clearances of beta-lactam
      antibiotics result in low troughs causing a reduced duration of antibiotic levels
      above the minimum inhibitory concentration (i.e. the suggested pharmacological
      target for these drugs). In critically ill patients frequent dosing or even
      continuous infusions of the beta-lactam antibiotics may increase their
      effectiveness by maintaining blood levels above the minimum inhibitory
      concentration (MIC) for longer periods. Vancomycin has a high volume of
      distribution in the critically ill patient, thus the currently recommended
      maximum daily dose may lead to inadequate serum levels. Suggested targets for
      quinolone therapy involve more than just high peak levels. A ratio of Area Under
      (serum) Concentration (AUC) time curve to MIC of >125 has been shown to correlate
      with better clinical outcomes. Ciprofloxacin when given intravenously at 400 mg 8
      hourly should achieve this, which is a regimen that has been shown to be safe.
      CONCLUSIONS: Applying pharmacokinetic and pharmacodynamic principles to
      critically ill patients will lead to better antibiotic use and hopefully a better
      outcome.

PMID- 16597317
TI  - Quality control, audit, adverse events and risk in the intensive care unit.

PMID- 16597316
TI  - Acute venous thromboembolism.
AB  - OBJECTIVE: To review the recent advances in management of acute venous
      thromboembolism. DATA SOURCES: Articles and published reviews on venous
      thromboembolism, pulmonary embolism and deep vein thrombosis. SUMMARY OF REVIEW:
      Acute venous thromboembolism describes a group of disorders that include venous
      thrombosis (usually deep vein thrombosis) and pulmonary thromboembolism.
      Ultrasound supplemented by Doppler flow detection imaging has become the
      investigation of choice in the diagnosis of deep vein thrombosis and spiral
      volumetric computed tomography or ventilation perfusion scan (if the patient is
      haemodynamically stable) or bedside echocardiography (if the patient is
      hypotensive) are often the initial investigations in a patient who has a
      suspected pulmonary thromboembolism. Magnetic resonance venography has only
      recently been evaluated and may prove in future to be a valuable diagnostic test
      for both deep vein thrombosis and pulmonary thromboembolism. Treatment requires
      immediate anticoagulation using either subcutaneous low molecular weight heparin
      (e.g. enoxaparin 1 mg/kg 12-hourly or dalteparin 100 IU anti Xa/kg twice daily)
      or intravenous unfractionated heparin (80 U/kg as a bolus then 18 U/kg/hr and
      adjusted to keep the APTT 1.5-2x the control value). Oral anticoagulation using
      warfarin is started simultaneously with heparin. Fibrinolytic therapy is
      considered in all patients with pulmonary thromboembolism in whom there are no
      contraindications, as the improvement in right ventricular function is greater
      and the pulmonary artery perfusion defect is less compared with patients treated
      by anticoagulation alone. Fibrinolytic therapy is usually only considered in
      patients with deep vein thrombosis if severe limb oedema is present. While
      streptokinase, urokinase and alteplase have been recommended, alteplase (100 mg
      over two hours with heparinisation) may be the treatment of choice as alteplase
      has a shorter half life, has a more rapid effect and may be more effective in
      lysing older clots, when compared with streptokinase or urokinase. Reteplase (10
      U over 2 minutes followed by 10 U 30 minutes later) may be as effective as
      alteplase. CONCLUSIONS: Acute venous thromboembolism is a disorder that carries a
      high morbidity and mortality. Anticoagulation with or without fibrinolysis is the
      treatment of choice.

PMID- 16597318
TI  - A 57 year old woman admitted to the emergency department with hyponatraemia and
      hypoglycaemia.

PMID- 16597319
TI  - A 23 year old woman with a closed head injury who developed rapidly fluctuating
      sodium levels.

PMID- 16597320
TI  - Xenopus death-domain-containing proteins FADD and RIP1 synergistically activate
      JNK and NF-kappaB.
AB  - BACKGROUND INFORMATION: Death receptors (DRs) induce intracellular signalling
      upon engagement of their cognate ligands, leading to apoptosis, cell survival or
      pro-inflammatory responses. In mammals, DR signalling is mediated by the
      recruitment of several DD (death domain)-containing molecules, such as FADD (Fas
      associated DD) and RIP1 (receptor-interacting protein 1). RESULTS: To elucidate
      the molecular mechanisms of intracellular DR signalling in Xenopus, we have
      isolated cDNAs encoding xFADD (Xenopus FADD), and xRIP1 and its short isoform
      xRIP1beta, which is produced by alternative splicing of the xRIP1 gene. These DD
      containing proteins interacted with Xenopus DR members xDR-M1 and xDR-M2 through
      their DDs in co-transfected HEK-293T cells. Overexpression of xFADD activated not
      only xCaspase 8, but also AP-1 (activator protein 1), which reflects activation
      of JNK (c-Jun N-terminal kinase) and NF-kappaB (nuclear factor kappaB). A
      comparative analysis of xRIP1, a kinase-dead mutant of xRIP1 and xRIP1beta
      indicated that the kinase activity of xRIP1 was required for the activation of AP
      1 and NF-kappaB. Interestingly, xFADD and xRIP1 interacted with each other via
      their DDs, and the expression of a mutant xRIP1 containing only the DD (xRIP1-DD)
      repressed the xFADD-induced activation of NF-kappaB and AP-1. xFADD and xRIP1
      synergistically induced the activation of AP-1 and NF-kappaB, both of which were
      partially mediated by TRAF2 (tumour-necrosis-factor-receptor-associated factor 2)
      and TAK1 (transforming-growth-factor-beta-activated kinase 1). We also found that
      the activation pathways of NF-kappaB induced by xDR-M2 were inhibited by xRIP1
      DD. CONCLUSIONS: Xenopus FADD, RIP1 and its splice variant RIP1beta have been
      characterized. Interaction of xFADD and xRIP1 induced synergistic activation of
      JNK and NF-kappaB. In addition, the NF-kappaB activation induced by xDR-M2 was
      partially mediated by xRIP1.

PMID- 16597321
TI  - Iron and infection: effects of host iron status and the iron-regulatory genes
      haptoglobin and NRAMP1 (SLC11A1) on host-pathogen interactions in tuberculosis
      and HIV.
AB  - There are many lines of evidence illustrating that iron plays a pivotal role in
      modulating the battle for survival between mammalian hosts and their pathogens.
      Each displays considerable genetic investment in a wide range of mechanisms for
      acquiring and maintaining iron. These competitive mechanisms are highly complex,
      existing within an interacting matrix of absorption, transport, storage and
      detoxification systems, each of which are iron-responsive and thus able to adapt
      to the different phases of infection. Considerable genetic polymorphism in some
      of these systems, with signals of geographic selection in the hosts, and niche
      selection in the pathogens, indicates that they are critical for species
      survival. In this review we briefly summarize the role of iron in host immune
      function before reviewing the available evidence that iron modulates
      susceptibility and disease outcomes in HIV and TB (tuberculosis). We then examine
      the putative role of iron-related host genes by focussing on two candidate genes,
      haptoglobin and NRAMP1, for which there are common polymorphic variants in humans
      with strong evidence of functionally distinct biochemical phenotypes that would
      be predicted to influence the course of HIV and TB infections. Finally, we
      examine the limited evidence so far available that nutrient-gene interactions are
      likely to influence the way in which gene variants can protect against infection.
      We conclude that there is a wealth of evidence associating alterations in iron
      balance and in iron-regulatory systems with disease progression, but that many
      issues related to the direction of causality, mechanisms of action and
      sensitivity to pharmacological intervention remain to be elucidated. Since iron
      is probably the most widely prescribed compound throughout the world, used in
      both preventative and treatment regimens, a deeper understanding of the host
      pathogen interactions relating to iron constitutes an important area for both
      basic and clinical research.

PMID- 16597322
TI  - Molecular biology of human papillomavirus infection and cervical cancer.
AB  - HPVs (human papillomaviruses) infect epithelial cells and cause a variety of
      lesions ranging from common warts/verrucas to cervical neoplasia and cancer. Over
      100 different HPV types have been identified so far, with a subset of these being
      classified as high risk. High-risk HPV DNA is found in almost all cervical
      cancers (>99.7%), with HPV16 being the most prevalent type in both low-grade
      disease and cervical neoplasia. Productive infection by high-risk HPV types is
      manifest as cervical flat warts or condyloma that shed infectious virions from
      their surface. Viral genomes are maintained as episomes in the basal layer, with
      viral gene expression being tightly controlled as the infected cells move towards
      the epithelial surface. The pattern of viral gene expression in low-grade
      cervical lesions resembles that seen in productive warts caused by other HPV
      types. High-grade neoplasia represents an abortive infection in which viral gene
      expression becomes deregulated, and the normal life cycle of the virus cannot be
      completed. Most cervical cancers arise within the cervical transformation zone at
      the squamous/columnar junction, and it has been suggested that this is a site
      where productive infection may be inefficiently supported. The high-risk E6 and
      E7 proteins drive cell proliferation through their association with PDZ domain
      proteins and Rb (retinoblastoma), and contribute to neoplastic progression,
      whereas E6-mediated p53 degradation prevents the normal repair of chance
      mutations in the cellular genome. Cancers usually arise in individuals who fail
      to resolve their infection and who retain oncogene expression for years or
      decades. In most individuals, immune regression eventually leads to clearance of
      the virus, or to its maintenance in a latent or asymptomatic state in the basal
      cells.

PMID- 16597323
TI  - Human papillomavirus in cervical screening and vaccination.
AB  - Recent decades have witnessed a reduction in the incidence of cervical cancer in
      countries where screening programmes have achieved broad coverage. The recognized
      importance of high-risk HPV (human papillomavirus) infection in the aetiology of
      cervical cancer may introduce a role for HPV DNA testing in cervical screening
      programmes. Positive HPV DNA tests indicate women at risk of cervical cancer with
      greater sensitivity, but reduced specificity, compared with exfoliative cytology.
      Combining HPV testing with cytology may be useful in the triage of minor
      cytological abnormalities into those requiring referral to colposcopy (HPV
      positive) compared with those who can be safely managed by cytological
      surveillance (HPV negative). With its high sensitivity and high-negative
      predictive value, HPV testing may also be useful for predicting treatment
      failure, since residual disease is very unlikely in the event of a negative HPV
      test. Ultimately, prevention is better than cure, and the advent of HPV
      prophylactic vaccines may obviate the need for population-based cervical
      screening programmes in the future. A multivalent vaccine administered to
      adolescents prior to the onset of sexual activity and boosted at regular
      intervals throughout their sexually active life may provide protection against
      type-specific HPV infection, malignant precursors and invasive cervical disease.
      Several large randomized placebo-controlled trials have been conducted with
      promising results. For those generations of women already exposed to high-risk
      HPV infection, therapeutic vaccines may offer advantages over conventional
      treatment, although much work still needs to be done.

PMID- 16597325
TI  - Genetic analysis of male reproductive success in relation to density in the
      zebrafish, Danio rerio.
AB  - BACKGROUND: We used behavioural and genetic data to investigate the effects of
      density on male reproductive success in the zebrafish, Danio rerio. Based on
      previous measurements of aggression and courtship behaviour by territorial males,
      we predicted that they would sire more offspring than non-territorial males.
      RESULTS: Microsatellite analysis of paternity showed that at low densities
      territorial males had higher reproductive success than non-territorial males.
      However, at high density territorial males were no more successful than non
      territorials and the sex difference in the opportunity for sexual selection,
      based on the parameter Imates, was low. CONCLUSION: Male zebrafish exhibit two
      distinct mating tactics; territoriality and active pursuit of females. Male
      reproductive success is density dependent and the opportunity for sexual
      selection appears to be weak in this species.

PMID- 16597324
TI  - Social capital and health: does egalitarianism matter? A literature review.
AB  - The aim of the paper is to critically review the notion of social capital and
      review empirical literature on the association between social capital and health
      across countries. The methodology used for the review includes a systematic
      search on electronic databases for peer-reviewed published literature. We
      categorize studies according to level of analysis (single and multilevel) and
      examine whether studies reveal a significant health impact of individual and area
      level social capital. We compare the study conclusions according to the country's
      degrees of economic egalitarianism. Regardless of study design, our findings
      indicate that a positive association (fixed effect) exists between social capital
      and better health irrespective of countries degree of egalitarianism. However, we
      find that the between-area variance (random effect) in health tends to be lower
      in more egalitarian countries than in less egalitarian countries. Our tentative
      conclusion is that an association between social capital and health at the
      individual level is robust with respect to the degree of egalitarianism within a
      country. Area level or contextual social capital may be less salient in
      egalitarian countries in explaining health differences across places.

PMID- 16597326
TI  - Overexpression of endothelial nitric oxide synthase suppresses features of
      allergic asthma in mice.
AB  - BACKGROUND: Asthma is associated with airway hyperresponsiveness and enhanced T
      cell number/activity on one hand and increased levels of exhaled nitric oxide
      (NO) with expression of inducible NO synthase (iNOS) on the other hand. These
      findings are in paradox, as NO also relaxes airway smooth muscle and has
      immunosuppressive properties. The exact role of the endothelial NOS (eNOS)
      isoform in asthma is still unknown. We hypothezised that a delicate regulation in
      the production of NO and its bioactive forms by eNOS might be the key to the
      pathogenesis of asthma. METHODS: The contribution of eNOS on the development of
      asthmatic features was examined. We used transgenic mice that overexpress eNOS
      and measured characteristic features of allergic asthma after sensitisation and
      challenge of these mice with the allergen ovalbumin. RESULTS: eNOS overexpression
      resulted in both increased eNOS activity and NO production in the lungs. Isolated
      thoracic lymph nodes cells from eNOS overexpressing mice that have been
      sensitized and challenged with ovalbumin produced significantly less of the
      cytokines IFN-gamma, IL-5 and IL-10. No difference in serum IgE levels could be
      found. Further, there was a 50% reduction in the number of lymphocytes and
      eosinophils in the lung lavage fluid of these animals. Finally, airway
      hyperresponsiveness to methacholine was abolished in eNOS overexpressing mice.
      CONCLUSION: These findings demonstrate that eNOS overexpression attenuates both
      airway inflammation and airway hyperresponsiveness in a model of allergic asthma.
      We suggest that a delicate balance in the production of bioactive forms of NO
      derived from eNOS might be essential in the pathophysiology of asthma.

PMID- 16597328
TI  - Biphasic responses of the brachial artery diameter following forearm occlusion: a
      blunted response in the elderly.
AB  - BACKGROUND: The purpose was to examine the temporal response of the brachial
      artery diameter following 5 minutes of forearm occlusion in young men. A
      secondary objective was to compare the main features of the temporal pattern
      between young and old. METHODS: Sixteen young (28 +/- 8 yrs) and fifteen older
      (85 +/- 8 yrs) men underwent high-resolution ultrasonography of the brachial
      artery before and after five minutes of forearm occlusion. RESULTS: Following
      release of the pressure cuff the brachial artery diameter exhibits a temporal
      biphasic response. Initially, there is a significant reduction in brachial
      diameter (NIL) compared to baseline (BASE), followed by a rapid increase to a
      PEAK at 41 sec post release. When comparing the magnitude of the decrease in
      diameter and the Brachial Artery Flow Mediated Dilation (BAFMD) between Young and
      Old, older subjects demonstrated a blunted response (Magnitude of Decrease:
      Young: 2.0%; Old: 0.4%, p = 0.015, and BAFMD: Young: 7.7%; Old: 2.3%, p = 0.001).
      Finally, a significant relationship was noted between the magnitude of decrease
      and BAFMD (r = -0.44, p = 0.04). CONCLUSION: Examination of the temporal response
      of the brachial artery diameter following 5 minutes of forearm occlusion reveals
      a biphasic pattern in all participants. Specific features of this pattern are
      blunted in older adults compared with younger subjects. Finally, the magnitude of
      the drop in diameter following forearm occlusion correlates with the magnitude of
      the BAFMD.

PMID- 16597327
TI  - Algorithms for incorporating prior topological information in HMMs: application
      to transmembrane proteins.
AB  - BACKGROUND: Hidden Markov Models (HMMs) have been extensively used in
      computational molecular biology, for modelling protein and nucleic acid
      sequences. In many applications, such as transmembrane protein topology
      prediction, the incorporation of limited amount of information regarding the
      topology, arising from biochemical experiments, has been proved a very useful
      strategy that increased remarkably the performance of even the top-scoring
      methods. However, no clear and formal explanation of the algorithms that retains
      the probabilistic interpretation of the models has been presented so far in the
      literature. RESULTS: We present here, a simple method that allows incorporation
      of prior topological information concerning the sequences at hand, while at the
      same time the HMMs retain their full probabilistic interpretation in terms of
      conditional probabilities. We present modifications to the standard Forward and
      Backward algorithms of HMMs and we also show explicitly, how reliable predictions
      may arise by these modifications, using all the algorithms currently available
      for decoding HMMs. A similar procedure may be used in the training procedure,
      aiming at optimizing the labels of the HMM's classes, especially in cases such as
      transmembrane proteins where the labels of the membrane-spanning segments are
      inherently misplaced. We present an application of this approach developing a
      method to predict the transmembrane regions of alpha-helical membrane proteins,
      trained on crystallographically solved data. We show that this method compares
      well against already established algorithms presented in the literature, and it
      is extremely useful in practical applications. CONCLUSION: The algorithms
      presented here, are easily implemented in any kind of a Hidden Markov Model,
      whereas the prediction method (HMM-TM) is freely available for academic users at
      http://bioinformatics.biol.uoa.gr/HMM-TM, offering the most advanced decoding
      options currently available.

PMID- 16597329
TI  - Measuring troublesomeness of chronic pain by location.
AB  - BACKGROUND: Current measures of pain assess the relative contribution of pain in
      different body regions to the overall impact of pain. We developed a series of
      questions to measure the relative 'troublesomeness' of pain in different body
      regions (the "troublesomeness grid"). The study aimed to determine whether the
      "troublesomeness grid" is an appropriate measure to assess the severity of pain
      in different body regions, allowing the comparative severity of pain in different
      body regions to be assessed. METHODS: We used data from a pilot for a population
      survey of pain (N = 205) and from the population survey itself (N = 2504) to
      assess the 'troublesomeness grid's performance. Specifically, its face and
      content validity using overall and item non-completion rates; its criterion
      related validity by exploring the relationship between troublesomeness and
      standard measures of pain, disability, distress and health utility for the five
      body regions most commonly affected by chronic pain; and its reliability and
      reproducibility in a test/re-test study. RESULTS: The troublesomeness grid
      appeared to have good face validity as it had good completion rates. It also
      appeared to have good content validity as the percentage agreement between the
      grid and the pain manikin was high (over 90%). In terms of criterion related
      validity, troublesomeness was most strongly correlated with pain intensity and
      health related quality of life, but less with disability and distress. The test
      retest reliability was between 80% and 90% for the majority of body regions
      examined. CONCLUSION: The troublesomeness grid is well completed and appears to
      be an appropriate tool to assess the comparative severity of pain in different
      body regions.

PMID- 16597331
TI  - Identifying strategies to improve access to credible and relevant information for
      public health professionals: a qualitative study.
AB  - BACKGROUND: Movement towards evidence-based practices in many fields suggests
      that public health (PH) challenges may be better addressed if credible
      information about health risks and effective PH practices is readily available.
      However, research has shown that many PH information needs are unmet. In addition
      to reviewing relevant literature, this study performed a comprehensive review of
      existing information resources and collected data from two representative PH
      groups, focusing on identifying current practices, expressed information needs,
      and ideal systems for information access. METHODS: Nineteen individual interviews
      were conducted among employees of two domains in a state health department-
      communicable disease control and community health promotion. Subsequent focus
      groups gathered additional data on preferences for methods of information access
      and delivery as well as information format and content. Qualitative methods were
      used to identify themes in the interview and focus group transcripts. RESULTS:
      Informants expressed similar needs for improved information access including
      single portal access with a good search engine; automatic notification regarding
      newly available information; access to best practice information in many areas of
      interest that extend beyond biomedical subject matter; improved access to grey
      literature as well as to more systematic reviews, summaries, and full-text
      articles; better methods for indexing, filtering, and searching for information;
      and effective ways to archive information accessed. Informants expressed a
      preference for improving systems with which they were already familiar such as
      PubMed and listservs rather than introducing new systems of information
      organization and delivery. A hypothetical ideal model for information
      organization and delivery was developed based on informants' stated information
      needs and preferred means of delivery. Features of the model were endorsed by the
      subjects who reviewed it. CONCLUSION: Many critical information needs of PH
      practitioners are not being met efficiently or at all. We propose a dual strategy
      of: 1) promoting incremental improvements in existing information delivery
      systems based on the expressed preferences of the PH users of the systems and 2)
      the concurrent development and rigorous evaluation of new models of information
      organization and delivery that draw on successful resources already operating to
      deliver information to clinical medical practitioners.

PMID- 16597330
TI  - Three novel and the common Arg677Ter RP1 protein truncating mutations causing
      autosomal dominant retinitis pigmentosa in a Spanish population.
AB  - BACKGROUND: Retinitis pigmentosa (RP), a clinically and genetically heterogeneous
      group of retinal degeneration disorders affecting the photoreceptor cells, is one
      of the leading causes of genetic blindness. Mutations in the photoreceptor
      specific gene RP1 account for 3-10% of cases of autosomal dominant RP (adRP).
      Most of these mutations are clustered in a 500 bp region of exon 4 of RP1.
      METHODS: Denaturing gradient gel electrophoresis (DGGE) analysis and direct
      genomic sequencing were used to evaluate the 5' coding region of exon 4 of the
      RP1 gene for mutations in 150 unrelated index adRP patients. Ophthalmic and
      electrophysiological examination of RP patients and relatives according to pre
      existing protocols were carried out. RESULTS: Three novel disease-causing
      mutations in RP1 were detected: Q686X, K705fsX712 and K722fsX737, predicting
      truncated proteins. One novel missense mutation, Thr752Met, was detected in one
      family but the mutation does not co-segregate in the family, thereby excluding
      this amino acid variation in the protein as a cause of the disease. We found the
      Arg677Ter mutation, previously reported in other populations, in two independent
      families, confirming that this mutation is also present in a Spanish population.
      CONCLUSION: Most of the mutations reported in the RP1 gene associated with adRP
      are expected to encode mutant truncated proteins that are approximately one third
      or half of the size of wild type protein. Patients with mutations in RP1 showed
      mild RP with variability in phenotype severity. We also observed several cases of
      non-penetrant mutations.

PMID- 16597332
TI  - Balance in single-limb stance after surgically treated ankle fractures: a 14
      month follow-up.
AB  - BACKGROUND: The maintenance of postural control is fundamental for different
      types of physical activity. This can be measured by having subjects stand on one
      leg on a force plate. Many studies assessing standing balance have previously
      been carried out in patients with ankle ligament injuries but not in patients
      with ankle fractures. The aim of this study was to evaluate whether patients
      operated on because of an ankle fracture had impaired postural control compared
      to an uninjured age- and gender-matched control group. METHODS: Fifty-four
      individuals (patients) operated on because of an ankle fracture were examined 14
      months postoperatively. Muscle strength, ankle mobility, and single-limb stance
      on a force-platform were measured. Average speed of centre of pressure movements
      and number of movements exceeding 10 mm from the mean value of centre of pressure
      were registered in the frontal and sagittal planes on a force-platform. Fifty
      four age- and gender-matched uninjured individuals (controls) were examined in
      the single-limb stance test only. The paired Student t-test was used for
      comparisons between patients' injured and uninjured legs and between side-matched
      legs within the controls. The independent Student t-test was used for comparisons
      between patients and controls. The Chi-square test, and when applicable, Fisher's
      exact test were used for comparisons between groups. Multiple logistic regression
      was performed to identify factors associated with belonging to the group unable
      to complete the single-limb stance test on the force-platform. RESULTS: Fourteen
      of the 54 patients (26%) did not manage to complete the single-limb stance test
      on the force-platform, whereas all controls managed this (p < 0.001). Age over 45
      years was the only factor significantly associated with not managing the test.
      When not adjusted for age, decreased strength in the ankle plantar flexors and
      dorsiflexors was significantly associated with not managing the test. In the 40
      patients who managed to complete the single-limb stance test no differences were
      found between the results of patients' injured leg and the side-matched leg of
      the controls regarding average speed and the number of centre of pressure
      movements. CONCLUSION: One in four patients operated on because of an ankle
      fracture had impaired postural control compared to an age- and gender-matched
      control group. Age over 45 years and decreased strength in the ankle plantar
      flexors and dorsiflexors were found to be associated with decreased balance
      performance. Further, longitudinal studies are required to evaluate whether
      muscle and balance training in the rehabilitation phase may improve postural
      control.

PMID- 16597333
TI  - Selection of SNP subsets for association studies in candidate genes: comparison
      of the power of different strategies to detect single disease susceptibility
      locus effects.
AB  - BACKGROUND: The recent advances in genotyping and molecular techniques have
      greatly increased the knowledge of the human genome structure. Millions of
      polymorphisms are reported and freely available in public databases. As a result,
      there is now a need to identify among all these data, the relevant markers for
      genetic association studies. Recently, several methods have been published to
      select subsets of markers, usually Single Nucleotide Polymorphisms (SNPs), that
      best represent genetic polymorphisms in the studied candidate gene or region.
      RESULTS: In this paper, we compared four of these selection methods, two based on
      haplotype information and two based on pairwise linkage disequilibrium (LD). The
      methods were applied to the genotype data on twenty genes with different patterns
      of LD and different numbers of SNPs. A measure of the efficiency of the different
      methods to select SNPs was obtained by comparing, for each gene and under several
      single disease susceptibility models, the power to detect an association that
      will be achieved with the selected SNP subsets. CONCLUSION: None of the four
      selection methods stands out systematically from the others. Methods based on
      pairwise LD information turn out to be the most interesting methods in a context
      of association study in candidate gene. In a context where the number of SNPs to
      be tested in a given region needs to be more limited, as in large-scale studies
      or wide genome scans, one of the two methods based on haplotype information,
      would be more suitable.

PMID- 16597335
TI  - Evaluation of wound healing activity of Allamanda cathartica. L. and Laurus
      nobilis. L. extracts on rats.
AB  - BACKGROUND: Allamanda cathartica. L. is a perennial shrub used in traditional
      medicine for treating malaria and jaundice. Laurus nobilis. L. is a tree and has
      been used for its astringent, healing and diuretic properties. The objective of
      this study was to investigate the aqueous extracts of Allamanda and Laurus
      nobilis to evaluate their wound healing activity in rats. METHODS: Excision and
      incision wound models were used to evaluate the wound healing activity of both
      the extracts on Sprague Dawley rats. In each model, animals were divided into
      four groups of 10 animals each. In both the model, group 1 served as control and
      group 2 as reference standard. In an excision wound model, group 3 animals were
      treated with Allamanda (150 mg kg(-1) day(-1)) and group 4 animals were treated
      with Laurus nobilis (200 mg kg(-1) b.w day(-1)) for 14 days respectively. In the
      case of incision wound model, group 3 and 4 animals were treated with the
      extracts of Allamanda and Laurus respectively for 10 days. The effects of
      vehicles on the rate of wound healing were assessed by the rate of wound closure,
      period of epithelialisation, tensile strength, weights of the granulation tissue,
      hydroxyproline content and histopathology of the granulation tissue. RESULTS: The
      aqueous extract of Allamanda promoted wound healing activity significantly in
      both the wound models studied. High rate of wound contraction (P < .001),
      decrease in the period of epithelialisation (10.2 +/- 0.13), high skin breaking
      strength (440.0 +/- 4.53), significant increase in the weight of the granulation
      tissue (P < .001) and hydroxyproline (P < .001) content were observed in animals
      treated with the aqueous extract of Allamanda. Histological studies of the
      granulation tissue from the Allamanda treated group showed the presence of a
      lesser number of inflammatory cells, and increased collagen formation than the
      control. In Laurus nobilis treated animals, the rate of wound contraction, weight
      of the granulation tissue and hydroxyproline content were moderately high (P <
      .05). The histological study of the granulation tissue of the Laurus nobilis
      treated animals showed larger number of inflammatory cells, and lesser collagen
      when compared with the Allamanda treated group of animals. However, it was better
      than the control group of animals. CONCLUSION: The data of this study indicated
      that the leaf extract of Allamanda possesses better wound healing activity than
      the Laurus nobilis and it can be used to treat different types of wounds in human
      beings too.

PMID- 16597334
TI  - Methods underpinning national clinical guidelines for hypertension: describing
      the evidence shortfall.
AB  - BACKGROUND: To be useful, clinical practice guidelines need to be evidence based;
      otherwise they will not achieve the validity, reliability and credibility
      required for implementation. METHODS: This paper compares the methods used in
      gathering, analysing and linking of evidence to guideline recommendations in ten
      current hypertension guidelines. RESULTS: It found several guidelines had failed
      to implement methods of searching for the relevant literature, critical analysis
      and linking to recommendations that minimise the risk of bias in the
      interpretation of research evidence. The more rigorous guidelines showed
      discrepancies in recommendations and grading that reflected different approaches
      to the use of evidence in guideline development. CONCLUSION: Clinical practice
      guidelines as a methodology are clearly still an evolving health care technology.

PMID- 16597336
TI  - MIMAS: an innovative tool for network-based high density oligonucleotide
      microarray data management and annotation.
AB  - BACKGROUND: The high-density oligonucleotide microarray (GeneChip) is an
      important tool for molecular biological research aiming at large-scale detection
      of small nucleotide polymorphisms in DNA and genome-wide analysis of mRNA
      concentrations. Local array data management solutions are instrumental for
      efficient processing of the results and for subsequent uploading of data and
      annotations to a global certified data repository at the EBI (ArrayExpress) or
      the NCBI (GeneOmnibus). DESCRIPTION: To facilitate and accelerate annotation of
      high-throughput expression profiling experiments, the Microarray Information
      Management and Annotation System (MIMAS) was developed. The system is fully
      compliant with the Minimal Information About a Microarray Experiment (MIAME)
      convention. MIMAS provides life scientists with a highly flexible and focused
      GeneChip data storage and annotation platform essential for subsequent analysis
      and interpretation of experimental results with clustering and mining tools. The
      system software can be downloaded for academic use upon request. CONCLUSION:
      MIMAS implements a novel concept for nation-wide GeneChip data management whereby
      a network of facilities is centered on one data node directly connected to the
      European certified public microarray data repository located at the EBI. The
      solution proposed may serve as a prototype approach to array data management
      between research institutes organized in a consortium.

PMID- 16597337
TI  - Assessing record linkage between health care and Vital Statistics databases using
      deterministic methods.
AB  - BACKGROUND: We assessed the linkage and correct linkage rate using deterministic
      record linkage among three commonly used Canadian databases, namely, the
      population registry, hospital discharge data and Vital Statistics registry.
      METHODS: Three combinations of four personal identifiers (surname, first name,
      sex and date of birth) were used to determine the optimal combination. The
      correct linkage rate was assessed using a unique personal health number available
      in all three databases. RESULTS: Among the three combinations, the combination of
      surname, sex, and date of birth had the highest linkage rate of 88.0% and 93.1%,
      and the second highest correct linkage rate of 96.9% and 98.9% between the
      population registry and Vital Statistics registry, and between the hospital
      discharge data and Vital Statistics registry in 2001, respectively. Adding the
      first name to the combination of the three identifiers above increased correct
      linkage by less than 1%, but at the cost of lowering the linkage rate almost by
      10%. CONCLUSION: Our findings suggest that the combination of surname, sex and
      date of birth appears to be optimal using deterministic linkage. The linkage and
      correct linkage rates appear to vary by age and the type of database, but not by
      sex.

PMID- 16597338
TI  - Detection of atovaquone-proguanil resistance conferring mutations in Plasmodium
      falciparum cytochrome b gene in Luanda, Angola.
AB  - BACKGROUND: The fixed dose combination atovaquone-proguanil is a recently
      introduced antimalarial for treatment and prophylaxis of Plasmodium falciparum
      malaria. It is highly effective with a good tolerability profile and a convenient
      prophylactic regimen. Nevertheless, cases of treatment failure have already been
      reported, which have been associated to mutations in the cytochrome b gene of the
      Plasmodium (pfcytb). The presence of atovaquone-proguanil in vivo resistance
      conferring mutations in pfcytb gene in Luanda, Angola, was investigated, in order
      to make recommendations on prescribing this antimalarial as prophylaxis for
      travellers. METHODS: Two hundred and forty nine blood samples from children
      hospitalized at Luanda Pediatric Hospital for malaria were studied. The PCR-RFLP
      methodology was used in order to identify pfcytb wild type codon 268 and two
      point mutations: T802A and A803C. RESULTS: All samples were identified as wild
      type for pfcytb gene at codon 268. In the studied population, no mutations
      associated to atovaquone-proguanil treatment failure were found. Prevalence of
      the studied mutations in the region was estimated to be less than 0.77% (99%
      significance level). CONCLUSION: Atovaquone-proguanil can be recommended for use
      by travellers to Luanda with expected high efficacy. This represents an
      improvement compared to other currently used prophylactic antimalarials in this
      region. However, it is imperative to continue surveillance.

PMID- 16597339
TI  - Present state of reproductive medicine in Japan - ethical issues with a focus on
      those seen in court cases.
AB  - BACKGROUND: Against a background of on the one hand, a declining demography and a
      conservative family register system that emphasizes the importance of the blood
      line, and on the other hand, an increase in the number of people undergoing
      fertility treatment, the absence of a legal regulatory framework concerning ART
      matters is likely to result in an increasing number of contradictory situations.
      It is against this background that the paper sets out to examine the judgements
      of court cases related to ART, with a particular focus on the legal determination
      of parental status, and to link these to aspects of the legal and socio-ethical
      environment within which the courts make their judgements. METHODS: The methods
      used were thorough investigation of all the court cases concerning ART in the
      public domain in Japan, including the arguments of the concerned parties and the
      judgements so far delivered. With the court cases as a central focal point,
      trends in Japan, including deliberations by government and academic societies,
      are reviewed, and the findings of surveys on the degree of understanding and
      attitudes among the people toward ART are summarized. RESULTS: In terms of the
      judgements to date, the central criteria used by the courts in determining
      parental status were the act of parturition and the consent of the husband of the
      concerned couple. The government and academic societies have displayed a cautious
      attitude toward ART, but the findings of attitude surveys among the people at
      large show a generally positive attitude toward ART. Attitudes toward the
      overwhelming importance hitherto attached to the bloodline are also seen to be
      changing. CONCLUSION: The main conclusion is that in the absence of a legal
      regulatory framework for ART, there is likely to be an increase in the
      contradictions between the use of outdated legal precedents and the technical
      development of ART. Since much of the specialist discussion necessary for the
      formulation of a legal framework has already been carried out, the speedy
      enactment of comprehensive and at the same time flexible legislation would be
      highly desirable, but further wide-ranging discussion involving the general
      public is likely to be needed first.

PMID- 16597340
TI  - Binary gene induction and protein expression in individual cells.
AB  - BACKGROUND: Eukaryotic gene transcription is believed to occur in either a binary
      or a graded fashion. With binary induction, a transcription activator (TA)
      regulates the probability with which a gene template is switched from the
      inactive to the active state without affecting the rate at which RNA molecules
      are produced from the template. With graded, also called rheostat-like, induction
      the gene template has continuously varying levels of transcriptional activity,
      and the TA regulates the rate of RNA production. Support for each of these two
      mechanisms arises primarily from experimental studies measuring reporter proteins
      in individual cells, rather than from direct measurement of induction events at
      the gene template. METHODS AND RESULTS: In this paper, using a computational
      model of stochastic gene expression, we have studied the biological and
      experimental conditions under which a binary induction mode operating at the gene
      template can give rise to differentially expressed "phenotypes" (i.e., binary,
      hybrid or graded) at the protein level. We have also investigated whether the
      choice of reporter genes plays a significant role in determining the observed
      protein expression patterns in individual cells, given the diverse properties of
      commonly-used reporter genes. Our simulation confirmed early findings that the
      lifetimes of active/inactive promoters and half-lives of downstream mRNA/protein
      products are important determinants of various protein expression patterns, but
      showed that the induction time and the sensitivity with which the expressed genes
      are detected are also important experimental variables. Using parameter
      conditions representative of reporter genes including green fluorescence protein
      (GFP) and beta-galactosidase, we also demonstrated that graded gene expression is
      more likely to be observed with GFP, a longer-lived protein with low detection
      sensitivity. CONCLUSION: The choice of reporter genes may determine whether
      protein expression is binary, graded or hybrid, even though gene induction itself
      operates in an all-or-none fashion.

PMID- 16597341
TI  - Evaluation of PROforma as a language for implementing medical guidelines in a
      practical context.
AB  - BACKGROUND: PROforma is one of several languages that allow clinical guidelines
      to be expressed in a computer-interpretable manner. How these languages should be
      compared, and what requirements they should meet, are questions that are being
      actively addressed by a community of interested researchers. METHODS: We have
      developed a system to allow hypertensive patients to be monitored and assessed
      without visiting their GPs (except in the most urgent cases). Blood pressure
      measurements are performed at the patients' pharmacies and a web-based system,
      created using PROforma, makes recommendations for continued monitoring, and/or
      changes in medication. The recommendations and measurements are transmitted
      electronically to a practitioner with authority to issue and change
      prescriptions. We evaluated the use of PROforma during the knowledge acquisition,
      analysis, design and implementation of this system. The analysis focuses on the
      logical adequacy, heuristic power, notational convenience, and explanation
      support provided by the PROforma language. RESULTS: PROforma proved adequate as a
      language for the implementation of the clinical reasoning required by this
      project. However a lack of notational convenience led us to use UML activity
      diagrams, rather than PROforma process descriptions, to create the models that
      were used during the knowledge acquisition and analysis phases of the project.
      These UML diagrams were translated into PROforma during the implementation of the
      project. CONCLUSION: The experience accumulated during this study highlighted the
      importance of structure preserving design, that is to say that the models used in
      the design and implementation of a knowledge-based system should be structurally
      similar to those created during knowledge acquisition and analysis. Ideally the
      same language should be used for all of these models. This means that great
      importance has to be attached to the notational convenience of these languages,
      by which we mean the ease with which they can be read, written, and understood by
      human beings. The importance of notational convenience arises from the fact that
      a language used during knowledge acquisition and analysis must be intelligible to
      the potential users of a system, and to the domain experts who provide the
      knowledge that will be used in its construction.

PMID- 16597342
TI  - STEM: a tool for the analysis of short time series gene expression data.
AB  - BACKGROUND: Time series microarray experiments are widely used to study dynamical
      biological processes. Due to the cost of microarray experiments, and also in some
      cases the limited availability of biological material, about 80% of microarray
      time series experiments are short (3-8 time points). Previously short time series
      gene expression data has been mainly analyzed using more general gene expression
      analysis tools not designed for the unique challenges and opportunities inherent
      in short time series gene expression data. RESULTS: We introduce the Short Time
      series Expression Miner (STEM) the first software program specifically designed
      for the analysis of short time series microarray gene expression data. STEM
      implements unique methods to cluster, compare, and visualize such data. STEM also
      supports efficient and statistically rigorous biological interpretations of short
      time series data through its integration with the Gene Ontology. CONCLUSION: The
      unique algorithms STEM implements to cluster and compare short time series gene
      expression data combined with its visualization capabilities and integration with
      the Gene Ontology should make STEM useful in the analysis of data from a
      significant portion of all microarray studies. STEM is available for download for
      free to academic and non-profit users at http://www.cs.cmu.edu/~jernst/stem.

PMID- 16597343
TI  - Increased multiaxial lumbar motion responses during multiple-impulse mechanical
      force manually assisted spinal manipulation.
AB  - BACKGROUND: Spinal manipulation has been found to create demonstrable segmental
      and intersegmental spinal motions thought to be biomechanically related to its
      mechanisms. In the case of impulsive-type instrument device comparisons,
      significant differences in the force-time characteristics and concomitant motion
      responses of spinal manipulative instruments have been reported, but studies
      investigating the response to multiple thrusts (multiple impulse trains) have not
      been conducted. The purpose of this study was to determine multi-axial segmental
      and intersegmental motion responses of ovine lumbar vertebrae to single impulse
      and multiple impulse spinal manipulative thrusts (SMTs). METHODS: Fifteen
      adolescent Merino sheep were examined. Tri-axial accelerometers were attached to
      intraosseous pins rigidly fixed to the L1 and L2 lumbar spinous processes under
      fluoroscopic guidance while the animals were anesthetized. A hand-held
      electromechanical chiropractic adjusting instrument (Impulse) was used to apply
      single and repeated force impulses (13 total over a 2.5 second time interval) at
      three different force settings (low, medium, and high) along the posteroanterior
      axis of the T12 spinous process. Axial (AX), posteroanterior (PA), and medial
      lateral (ML) acceleration responses in adjacent segments (L1, L2) were recorded
      at a rate of 5000 samples per second. Peak-peak segmental accelerations (L1, L2)
      and intersegmental acceleration transfer (L1-L2) for each axis and each force
      setting were computed from the acceleration-time recordings. The initial
      acceleration response for a single thrust and the maximum acceleration response
      observed during the 12 multiple impulse trains were compared using a paired
      observations t-test (POTT, alpha = .05). RESULTS: Segmental and intersegmental
      acceleration responses mirrored the peak force magnitude produced by the Impulse
      Adjusting Instrument. Accelerations were greatest for AX and PA measurement axes.
      Compared to the initial impulse acceleration response, subsequent multiple SMT
      impulses were found to produce significantly greater (3% to 25%, P < 0.005) AX,
      PA and ML segmental and intersegmental acceleration responses. Increases in
      segmental motion responses were greatest for the low force setting (18%-26%),
      followed by the medium (5%-26%) and high (3%-26%) settings. Adjacent segment (L1)
      motion responses were maximized following the application of several multiple SMT
      impulses. CONCLUSION: Knowledge of the vertebral motion responses produced by
      impulse-type, instrument-based adjusting instruments provide biomechanical
      benchmarks that support the clinical rationale for patient treatment. Our results
      indicate that impulse-type adjusting instruments that deliver multiple impulse
      SMTs significantly increase multi-axial spinal motion.

PMID- 16597344
TI  - Use of antenatal services and delivery care among women in rural western Kenya: a
      community based survey.
AB  - BACKGROUND: Improving maternal health is one of the UN Millennium Development
      Goals. We assessed provision and use of antenatal services and delivery care
      among women in rural Kenya to determine whether women were receiving appropriate
      care. METHODS: Population-based cross-sectional survey among women who had
      recently delivered. RESULTS: Of 635 participants, 90% visited the antenatal
      clinic (ANC) at least once during their last pregnancy (median number of visits
      4). Most women (64%) first visited the ANC in the third trimester; a perceived
      lack of quality in the ANC was associated with a late first ANC visit (Odds ratio
      [OR] 1.5, 95% confidence interval [CI] 1.0-2.4). Women who did not visit an ANC
      were more likely to have < 8 years of education (adjusted OR [AOR] 3.0, 95% CI
      1.5-6.0), and a low socio-economic status (SES) (AOR 2.8, 95% CI 1.5-5.3). The
      ANC provision of abdominal palpation, tetanus vaccination and weight measurement
      were high (>90%), but provision of other services was low, e.g. malaria
      prevention (21%), iron (53%) and folate (44%) supplementation, syphilis testing
      (19.4%) and health talks (14.4%). Eighty percent of women delivered outside a
      health facility; among these, traditional birth attendants assisted 42%,
      laypersons assisted 36%, while 22% received no assistance. Factors significantly
      associated with giving birth outside a health facility included: age >or= 30
      years, parity >or= 5, low SES, < 8 years of education, and > 1 hour walking
      distance from the health facility. Women who delivered unassisted were more
      likely to be of parity >or= 5 (AOR 5.7, 95% CI 2.8-11.6). CONCLUSION: In this
      rural area, usage of the ANC was high, but this opportunity to deliver important
      health services was not fully utilized. Use of professional delivery services was
      low, and almost 1 out of 5 women delivered unassisted. There is an urgent need to
      improve this dangerous situation.

PMID- 16597345
TI  - Functional neuroanatomy of the rhinophore of Aplysia punctata.
AB  - BACKGROUND: For marine snails, olfaction represents a crucial sensory modality
      for long-distance reception, as auditory and visual information is limited. The
      posterior tentacle of Aplysia, the rhinophore, is a chemosensory organ and
      several behavioural studies showed that the rhinophores can detect pheromones,
      initiate orientation and locomotion toward food. However the functional
      neuroanatomy of the rhinophore is not yet clear. Here we apply serotonin
      immunohistochemistry and fluorescent markers in combination with confocal
      microscopy as well as optical recording techniques to elucidate the structure and
      function of the rhinophore of the sea slug Aplysia punctata. RESULTS: With
      anatomical techniques an overview of the neuroanatomical organization of the
      rhinophore is presented. Labelling with propidium iodide revealed one layer of
      cell nuclei in the sensory epithelium and densely packed cell nuclei beneath the
      groove of the rhinophore, which extends to about two third of the total length of
      the rhinophore. Serotonin immunoreactivity was found within the olfactory
      glomeruli underneath the epithelium as well as in the rhinophore ganglion.
      Retrograde tracing from the rhinophore ganglion with 4-(4
      (dihexadecylamino)styryl)-N-methylpyridinium iodide (DiA) demonstrated the
      connection of glomeruli with the ganglion. Around 36 glomeruli (mean diameter 49
      microm) were counted in a single rhinophore. Fluorimetric measurements of
      intracellular Ca2+ levels using Fura-2 AM loading revealed Ca2+-responses within
      the rhinophore ganglion to stimulation with amino acids. Bath application of
      different amino acids revealed differential responses at different positions
      within the rhinophore ganglion. CONCLUSION: Our neuroanatomical study revealed
      the number and position of glomeruli in the rhinophore and the rhinophore
      ganglion as processing stage of sensory information. Serotonin-immunoreactive
      processes were found extensively within the rhinophore, but was not detected
      within any peripheral cell body. Amino acids were used as olfactory stimuli in
      optical recordings and induced sensory responses in the rhinophore ganglion. The
      complexity of changes in intracellular Ca2+-levels indicates, that processing of
      odour information takes place within the rhinophore ganglion. Our neuroanatomical
      and functional studies of the rhinophore open up a new avenue to analyze the
      olfactory system in Aplysia.

PMID- 16597346
TI  - Gap junctional coupling and connexin immunoreactivity in rabbit retinal glia.
AB  - Gap junctions provide a pathway for the direct intercellular exchange of ions and
      small signaling molecules. Gap junctional coupling between retinal astrocytes and
      between astrocytes and Muller cells, the principal glia of vertebrate retinas,
      has been previously demonstrated by the intercellular transfer of gap-junction
      permeant tracers. However, functional gap junctions have yet to be demonstrated
      between mammalian Muller cells. In the present study, when the gap-junction
      permeant tracers Neurobiotin and Lucifer yellow were injected into a Muller cell
      via a patch pipette, the tracers transferred to at least one additional cell in
      more than half of the cases examined. Simultaneous whole-cell recordings from
      pairs of Muller cells in the isolated rabbit retina revealed electrical coupling
      between closely neighboring cells, confirming the presence of functional gap
      junctions between rabbit Muller cells. The limited degree of this coupling
      suggests that Muller cell-Muller cell gap junctions may coordinate the functions
      of small ensembles of these glial cells. Immunohistochemistry and immunoblotting
      were used to identify the connexins in rabbit retinal glia. Connexin30 (Cx30) and
      connexin43 (Cx43) immunoreactivities were associated with astrocytes in the
      medullary ray region of the retinas of both pigmented and albino rabbits.
      Connexin43 was also found in Muller cells, but antibody recognition differed
      between astrocytic and Muller cell connexin43.

PMID- 16597348
TI  - Photic history modifies susceptibility to retinal damage in albino trout.
AB  - Albino vertebrates exposed to intense light typically lose photoreceptors via
      apoptosis, and thus serve as useful models of retinal degeneration. In contrast,
      albino rainbow trout exposed to intense light maintain populations of rod and
      cone nuclei despite substantial damage to rod outer segments (ROS). The aim of
      this study was to differentiate between two hypotheses that could account for
      this divergent result: (1) trout rod nuclei remain intact during light damage, or
      (2) rod nuclei die but are replaced by cell proliferation. A further aim was to
      examine whether photic history modulates retinal damage, as in rodents. Albino
      and normally pigmented trout were moved from defined photic regimes into full
      daylight, while some were not moved to serve as protected controls. ROS were
      always maintained in pigmented fish and in albinos protected from full daylight.
      In albinos exposed to full daylight, ROS were removed over most of the central
      retina, whereas rod nuclei were maintained in the outer nuclear layer over 10
      days. Pyknotic and TUNEL-labeled rod nuclei were abundant in affected albinos at
      all time-points tested. Rod death occurred without a decrease in the number of
      rod nuclei, confirming that proliferation must be replacing cells. Indeed a
      transient increase in proliferation was observed in retinal progenitors of
      albinos receiving 5 days of damaging light. This proliferative response was
      decreased with further damage. Cones remained intact even in areas where rod
      nuclei had degenerated. Pretreatment with light of moderate versus low intensity
      light affected the cell death and proliferative responses, and the ectopic
      localization of rod opsin. We conclude that apoptotic demise of rods, but not
      cones, occurred during light damage in retinas of albino trout and proliferative
      responses have a limited a capacity to replace lost rods.

PMID- 16597349
TI  - Natural images and contrast encoding in bipolar cells in the retina of the land-
      and aquatic-phase tiger salamander.
AB  - Intracellular recordings were obtained from 57 cone-driven bipolar cells in the
      light-adapted retina of the land-phase (adult) tiger salamander (Ambystoma
      tigrinum). Responses to flashes of negative and positive contrast for centered
      spots of optimum spatial dimensions were analyzed as a function of contrast
      magnitude. On average, the contrast/response curves of depolarizing and
      hyperpolarizing bipolar cells in the land-phase animals were remarkably similar
      to those of aquatic-phase animals. Thus, the primary retinal mechanisms mediating
      contrast coding in the outer retina are conserved as the salamander evolves from
      the aquatic to the land phase. To evaluate contrast encoding in the context of
      natural environments, the distribution of contrasts in natural images was
      measured for 65 scenes. The results, in general agreement with other reports,
      show that the vast majority of contrasts in nature are very small. The efficient
      coding hypothesis of Laughlin was examined by comparing the average
      contrast/response curves of bipolar cells with the cumulative probability
      distribution of contrasts in natural images. Efficient coding was found at 20
      cd/m2 but at lower levels of light adaptation, the contrast/response curves were
      much too shallow. Further experiments show that two fundamental physiological
      factors-light adaptation and the nonlinear transfer across the cone-bipolar
      synapse are essential for the emergence of efficient contrast coding. For both
      land- and aquatic-based animals, the extent and symmetry of the dynamic range of
      the contrast/response curves of both classes of bipolar cells varied greatly from
      cell to cell. This apparent substrate for distributed encoding is established at
      the bipolar cell level, since it is not found in cones. As a result, the dynamic
      range of the bipolar cell population brackets the distribution of contrasts found
      in natural images.

PMID- 16597350
TI  - Radial motion bias in macaque frontal eye field.
AB  - The visual responsiveness and spatial tuning of frontal eye field (FEF) neurons
      were determined using a delayed memory saccade task. Neurons with visual
      responses were then tested for direction selectivity using moving random dot
      patterns centered in the visual receptive field. The preferred axis of motion
      showed a significant tendency to be aligned with the receptive-field location so
      as to favor motion toward or away from the center of gaze. Centrifugal (outward)
      motion was preferred over centripetal motion. Motion-sensitive neurons in FEF
      thus appear to have a direction bias at the population level. This bias may
      facilitate the detection or discrimination of expanding optic flow patterns. The
      direction bias is similar to that seen in visual area MT and in posterior
      parietal cortex, from which FEF receives afferent projections. The outward motion
      bias may explain asymmetries in saccades made to moving targets. A representation
      of optic flow in FEF might be useful for planning eye movements during
      navigation.

PMID- 16597347
TI  - The nob2 mouse, a null mutation in Cacna1f: anatomical and functional
      abnormalities in the outer retina and their consequences on ganglion cell visual
      responses.
AB  - Glutamate release from photoreceptor terminals is controlled by voltage-dependent
      calcium channels (VDCCs). In humans, mutations in the Cacna1f gene, encoding the
      alpha1F subunit of VDCCs, underlie the incomplete form of X-linked congenital
      stationary night blindness (CSNB2). These mutations impair synaptic transmission
      from rod and cone photoreceptors to bipolar cells. Here, we report anatomical and
      functional characterizations of the retina in the nob2 (no b-wave 2) mouse, a
      naturally occurring mutant caused by a null mutation in Cacna1f. Not
      surprisingly, the b-waves of both the light- and dark-adapted electroretinogram
      are abnormal in nob2 mice. The outer plexiform layer (OPL) is disorganized, with
      extension of ectopic neurites through the outer nuclear layer that originate from
      rod bipolar and horizontal cells, but not from hyperpolarizing bipolar cells.
      These ectopic neurites continue to express mGluR6, which is frequently associated
      with profiles that label with the presynaptic marker Ribeye, indicating potential
      points of ectopic synapse formation. However, the morphology of the presynaptic
      Ribeye-positive profiles is abnormal. While cone pedicles are present their
      morphology also appears compromised. Characterizations of visual responses in
      retinal ganglion cells in vivo, under photopic conditions, demonstrate that ON
      center cells have a reduced dynamic range, although their basic center-surround
      organization is retained; no alteration in the responses of OFF-center cells was
      evident. These results indicate that nob2 mice are a valuable model in which to
      explore the pathophysiological mechanisms associated with Cacna1f mutations
      causing CSNB2, and the subsequent effects on visual information processing.
      Further, the nob2 mouse represents a model system in which to define the signals
      that guide synapse formation and/or maintenance in the OPL.

PMID- 16597351
TI  - Retinotopic organization of ferret suprasylvian cortex.
AB  - The retinotopic organization of striate and several extrastriate areas of ferret
      cortex has been established. Here we describe the representation of the visual
      field on the Suprasylvian visual area (Ssy). This cortical region runs
      mediolaterally along the posterior bank of the suprasylvian sulcus, and is
      distinct from adjoining areas in anatomical architecture. The Ssy lies
      immediately rostral to visual area 21, medial to lateral temporal areas, and
      lateral to posterior parietal areas. In electrophysiological experiments we made
      extracellular recordings in adult ferrets. We find that single and multiunit
      receptive fields range in size from 2 deg x 4 deg to 21 deg x 52 deg. The total
      visual field representation in Ssy spans over 70 deg in azimuth in the
      contralateral hemifield (with a small incursion into the ipsilateral hemifield),
      and from +36 deg to -30 deg in elevation. There are often two representations of
      the horizontal meridian. Furthermore, the location of the transition from upper
      to lower fields varies among animals. General features of topography are
      confirmed in anatomical experiments in which we made tracer injections into
      different locations in Ssy, and determined the location of retrograde label in
      area 17. Both isoelevation and isoazimuth lines can span substantial rostrocaudal
      and mediolateral distances in cortex, sometimes forming closed contours. This
      topography results in cortical magnifications averaging 0.07 mm/deg in elevation
      and 0.06 mm/deg in azimuth; however, some contours can run in such a way that it
      is possible to move a large distance on cortex without moving in the visual
      field. Because of these irregularities, Ssy contains a coarse representation of
      the contralateral visual field.

PMID- 16597352
TI  - Ionotropic glutamate receptors of amacrine cells of the mouse retina.
AB  - The mammalian retina contains approximately 30 different morphological types of
      amacrine cells, receiving glutamatergic input from bipolar cells. In this study,
      we combined electrophysiological and pharmacological techniques in order to study
      the glutamate receptors expressed by different types of amacrine cells. Whole
      cell currents were recorded from amacrine cells in vertical slices of the mouse
      retina. During the recordings the cells were filled with Lucifer
      Yellow/Neurobiotin allowing classification as wide-field or narrow-field amacrine
      cells. Amacrine cell recordings were also carried out in a transgenic mouse line
      whose glycinergic amacrine cells express enhanced green fluorescent protein
      (EGFP). Agonist-induced currents were elicited by exogenous application of NMDA,
      AMPA, and kainate (KA) while holding cells at -75 mV. Using a variety of specific
      agonists and antagonists (NBQX, AP5, cyclothiazide, GYKI 52466, GYKI 53655, SYM
      2081) responses mediated by AMPA, KA, and NMDA receptors could be dissected. All
      cells (n = 300) showed prominent responses to non-NMDA agonists. Some cells
      expressed AMPA receptors exclusively and some cells expressed KA receptors
      exclusively. In the majority of cells both receptor types could be identified.
      NMDA receptors were observed in about 75% of the wide-field amacrine cells and in
      less than half of the narrow-field amacrine cells. Our results confirm that
      different amacrine cell types express distinct sets of ionotropic glutamate
      receptors, which may be critical in conferring their unique temporal responses to
      this diverse neuronal class.

PMID- 16597353
TI  - Long-term ERG analysis in the partially light-damaged mouse retina reveals
      regressive and compensatory changes.
AB  - Most of the blinding retinopathies are due to progressive photoreceptor
      degeneration. Treatment paradigms that are currently being investigated include
      strategies to either halt or slow down photoreceptor cell loss, or to replace
      useful vision with retinal prosthesis. However, more information is required on
      the pathophysiological changes of the diseased retina, in particular the inner
      retina, that occur as a consequence of photoreceptor cell loss. Here we wished to
      use light damage as a stoppable insult to determine the structural and functional
      consequences on inner and outer retina, with the overall goal of determining
      whether survival of a functional inner retina is possible even if the outer
      retina is damaged. Mice were exposed to a 20-day light-damage period.
      Electroretinograms (ERG) and morphology were used to assess subsequent recovery.
      Outer retina was monitored analyzing a-waves, which represent photoreceptor cell
      responses, and histology. Integrity of the inner retina was monitored, analyzing
      b-waves and oscillatory potentials (OP1-OP4) and immunohistochemical markers for
      known proteins of the inner retina. All six ERG components were significantly
      suppressed with respect to amplitudes and kinetics, but stabilized in a wave
      dependent manner within 40-70 days after the end of light exposure. As expected,
      damage of the outer retina was permanent. However, function of the inner retina
      was found to recover significantly. While b-wave amplitudes remained suppressed
      to 60% of their baseline values, OP amplitudes recovered completely, and implicit
      times of all components of the inner retina (b-wave and OP1-OP4) recovered to a
      level close to baseline values. Histological analyses confirmed the lack of
      permanent damage to the inner retina. In summary, these data suggests that the
      inner retina has the potential for significant recovery as well as plasticity if
      treatment is available to stop the deterioration of the outer retina.

PMID- 16597354
TI  - Cloning and molecular characterization of cGMP-gated ion channels from rod and
      cone photoreceptors of striped bass ( M. saxatilis ) retina.
AB  - Vertebrate photoreceptors respond to light with changes in membrane conductance
      that reflect the activity of cyclic-nucleotide gated channels (CNG channels). The
      functional features of these channels differ in rods and cones; to understand the
      basis of these differences we cloned CNG channels from the retina of striped
      bass, a fish from which photoreceptors can be isolated and studied
      electrophysiologically. Through a combination of experimental approaches, we
      recovered and sequenced three full-length cDNA clones. We made unambiguous
      assignments of the cellular origin of the clones through single photoreceptor RT
      PCR. Synthetic peptides derived from the sequence were used to generate
      monospecific antibodies which labeled intact, unfixed photoreceptors and
      confirmed the cellular assignment of the various clones. In rods, we identified
      the channel alpha subunit gene product as 2040 bp in length, transcribed into two
      mRNA 1.8 kb and 2.9 kb in length and translated into a single 96-kDa protein. In
      cones we identified both alpha (CNGA3) and beta (CNGB3) channel subunits. For
      alpha, the gene product is 1956 bp long, the mRNA 3.4 kb, and the protein 74 kDa.
      For beta, the gene product is 2265 bp long and the mRNA 3.3 kb. Based on deduced
      amino acid sequence, we developed a phylogenetic map of the evolution of
      vertebrate rod and cone CNG channels. Sequence comparison revealed channels in
      striped bass, unlike those in mammals, are likely not N-linked-glycosylated as
      they are transported within the photoreceptor. Also bass cone channels lack
      certain residues that, in mammals, can be phosphorylated and, thus, affect the
      cGMP sensitivity of gating. On the other hand, functionally critical residues,
      such as positively charged amino acids within the fourth transmembrane helix (S4)
      and the Ca(2+)-binding glutamate in the pore loop are absolutely the same in
      mammalian and nonmammalian species.

PMID- 16597355
TI  - Receptive-field structure of optic flow responsive Purkinje cells in the
      vestibulocerebellum of pigeons.
AB  - Neurons sensitive to optic flow patterns have been recorded in the the olivo
      vestibulocerebellar pathway and extrastriate visual cortical areas in
      vertebrates, and in the visual neuropile of invertebrates. The complex spike
      activity (CSA) of Purkinje cells in the vestibulocerebellum (VbC) responds best
      to patterns of optic flow that result from either self-rotation or self
      translation. Previous studies have suggested that these neurons have a receptive
      field (RF) structure that "approximates" the preferred optic flowfield with a
      "bipartite" organization. Contrasting this, studies in invertebrate species
      indicate that optic flow sensitive neurons are precisely tuned to their preferred
      flowfield, such that the local motion sensitivities and local preferred
      directions within their RFs precisely match the local motion in that region of
      the preferred flowfield. In this study, CSA in the VbC of pigeons was recorded in
      response to a set of complex computer-generated optic flow stimuli, similar to
      those used in previous studies of optic flow neurons in primate extrastriate
      visual cortex, to test whether the receptive field was of a precise or bipartite
      organization. We found that these RFs were not precisely tuned to optic flow
      patterns. Rather, we conclude that these neurons have a bipartite RF structure
      that approximates the preferred optic flowfield by pooling motion subunits of
      only a few different direction preferences.

PMID- 16597356
TI  - Unique functional properties of the APB sensitive and insensitive rod pathways
      signaling light decrements in mouse retinal ganglion cells.
AB  - Light decrements are mediated by two distinct groups of rod pathways in the dark
      adapted retina that can be differentiated on the basis of their sensitivity to
      the glutamate agonist DL-2-amino-phosphonobutyric (APB). By means of the APB
      sensitive pathway, rods transmit light decrements via rod bipolar cells to AII
      amacrine cells, then to Off cone bipolar cells, which in turn innervate the
      dendrites of Off ganglion cells. APB hyperpolarizes rod bipolar cells, thus
      blocking this rod pathway. With APB insensitive pathways, rods either directly
      synapse onto Off cone bipolar cells, or rods pass light decrement signal to cones
      by gap junctions. In the present study, whole-cell patch-clamp recordings were
      made from ganglion cells in the dark-adapted mouse retina to investigate the
      functional properties of APB sensitive and insensitive rod pathways. The results
      revealed several clear-cut differences between the APB sensitive and APB
      insensitive rod pathways. The latency of Off responses to a flashing spot of
      light was significantly shorter for the APB insensitive pathways than those for
      the APB sensitive pathway. Moreover, Off responses of the APB insensitive
      pathways were found to be capable of following substantially higher stimulus
      frequencies. Nitric oxide was found to selectively block Off responses in the APB
      sensitive rod pathway. Collectively, these results provide evidence that the APB
      sensitive and insensitive rod pathways can convey different types of information
      signaling light decrements in the dark-adapted retina.

PMID- 16597357
TI  - Expansion of visual receptive fields in experimental glaucoma.
AB  - Glaucoma is a major cause of blindness and is characterized by death of retinal
      ganglion cells. In a rat model of glaucoma in which intraocular pressure is
      raised by cautery of episcleral veins, the somata and dendritic arbors of
      surviving retinal ganglion cells expand. To assess physiological consequences of
      this change, we have measured visual receptive-field size in a primary retinal
      target, the superior colliculus. Using multiunit recording, receptive-field sizes
      were measured for glaucomatous eyes and compared to both those measured for
      contralateral control eyes and to homolateral eyes of unoperated animals.
      Episcleral vein occlusion increased intraocular pressure. This was accompanied by
      a significant increase in receptive-field size across the superior colliculus.
      The expansion of receptive fields was proportional to both degree and duration of
      the increase of intraocular pressure. We suggest that this increase in the size
      of receptive fields of glaucomatous eyes may be related to the increase in the
      size of dendritic arbors of the surviving ganglion cells in retina.

PMID- 16597358
TI  - Stage-specific differences in fecundity over the life-cycle of two characterized
      isolates of the liver fluke, Fasciola hepatica.
AB  - The variability inherent in different isolates of Fasciola hepatica has been
      evident from reports in the literature but to date there has been no systematic
      examination of the relationship between these differences and the fecundity of
      the parasite. In this study we have attempted to remedy this situation by
      comparing the relative efficiencies with which 2 well-characterized isolates of
      the liver fluke (Oberon and Fairhurst) progress through both their definitive and
      intermediate hosts. We did not observe a reduction in fitness in the Oberon
      isolate which has been reported to be triclabendazole-resistant, compared to the
      triclabendazole-susceptible Fairhurst isolate, but considerable inter- and intra
      isolate variability at different life-cycle stages was recorded. Thus the Oberon
      isolate gave 4-fold the number of cercariae when 100 snails were each challenged
      with a single miracidium and was more successful in establishing productive
      infections in rats. Fairhurst metacercariae excysted at a higher rate than those
      from the Oberon isolate and Fairhurst flukes produced 4-fold more eggs. The
      extent of the intra- and inter-isolate variability revealed in this work will
      provide a basis for the development of models of population dynamics aimed at
      predicting the response of the liver fluke to changing environmental conditions
      such as the use of anthelmintics or climatic change.

PMID- 16597359
TI  - Can drug-bearing liposomes penetrate intact skin?
AB  - Using liposomes to deliver drugs to and through human skin is controversial, as
      their function varies with type and composition. Thus they may act as drug
      carriers controlling release of the medicinal agent. Alternatively, they may
      provide a localized depot in the skin so minimizing systemic effects or can be
      used for targeting delivery to skin appendages (hair follicles and sweat glands).
      Liposomes may also enhance transdermal drug delivery, increasing systemic drug
      concentrations. With such a multiplicity of functions, it is not surprising that
      mechanisms of liposomal delivery of therapeutic agents to and through the skin
      are unclear. Accordingly, this article provides an overview of the modes and
      mechanisms of action of different vesicles as drug delivery vectors in human
      skin. Our conclusion is that vesicles, depending on the composition and method of
      preparation, can vary with respect to size, lamellarity, charge, membrane
      fluidity or elasticity and drug entrapment. This variability allows for multiple
      functions ranging from local to transdermal effects. Application to dissimilar
      skins (animal or human) via diverse protocols may reveal different mechanisms of
      action with possible vesicle skin penetration reaching different depths, from
      surface assimilation to (rarely) the viable tissue and subsequent systemic
      absorption.

PMID- 16597360
TI  - Significant and prolonged antisense effect of a multifunctional envelope-type
      nano device encapsulating antisense oligodeoxynucleotide.
AB  - A multifunctional envelope-type nano device (MEND) was developed for use as an
      efficient non-viral system for the delivery of plasmid DNA (pDNA) using
      octaarginine (R8) as an internalizing ligand. Three types of R8-MENDs were
      prepared, co-encapsulating luciferase-encoding pDNA and anti-luciferase
      oligodeoxynucleotide (ODN) condensed by three polycations, stearyl octaarginine
      (STRR8), poly-L-lysine (PLL) and protamine, and the antisense effects of the ODN
      encapsulated R8-MENDs (ODN-MEND) were analysed in-vitro. The ODN-MEND packaged
      using protamine as a condenser showed a 90% antisense effect 16 h after the
      transfection, and a persistent antisense effect of over 75% for up to 48 h, which
      was much more effective than that of LipofectAmine2000. On the other hand, the
      ODN-MENDs prepared using PLL and STR-R8 as condensers did not show any
      significant inhibition of luciferase activity. Although there was no specific
      relation between the physicochemical characteristics of the ODN-MENDs and their
      antisense effect, the pattern of the antisense effect among the ODN-MENDs was
      similar to that of the silencing effect of R8-MEND encapsulating plasmid DNA
      encoding siRNA. These results suggest that R8-MENDs are able to deliver
      encapsulated DNA to the cytosol as well as to the nucleus, and that protamine can
      also function as an efficient decondenser, not only in the nucleus but also in
      the cytosol. In conclusion, we successfully developed an ODN-MEND with a high
      antisense effect using protamine as a DNA condensing as well as a decondensing
      agent.

PMID- 16597361
TI  - Evaluation of the immune response induced by a nasal anthrax vaccine based on the
      protective antigen protein in anaesthetized and non-anaesthetized mice.
AB  - To better protect against inhalational anthrax infection, a nasal anthrax vaccine
      based on the protective antigen (PA) protein of Bacillus anthracis could be an
      attractive alternative to the current Anthrax-Vaccine-Adsorbed (AVA), which was
      licensed for cutaneous anthrax prevention. Previously, we have demonstrated that
      an anti-PA immune response comparable with that in mice subcutaneously immunized
      with PA protein adjuvanted with aluminium hydroxide was induced in both the
      systemic compartment and the mucosal secretions of the nose and lung of
      anaesthetized mice when they were nasally immunized with PA protein incorporated
      into previously reported LPD (Liposome-Protamine-DNA) particles. In this study,
      we evaluated the anti-PA immune response induced by the nasal PA/LPD particles in
      non-anaesthetized mice and compared it with that in anaesthetized mice. Our data
      showed that the anti-PA antibody response and the anthrax lethal toxin
      neutralization activity induced by the nasal PA/LPD in non-anaesthetized mice was
      relatively weaker than that in anaesthetized mice. However, the splenocytes
      isolated from the nasally immunized mice, anaesthetized and non-anaesthetized,
      proliferated comparably after in-vitro re-stimulation. By evaluating the uptake
      of fluorescence-labelled LPD particles by phagocytes in the nasal and broncho
      alveolar lavages of mice after the nasal administration, we concluded that the
      relatively weaker anti-PA immune response in the non-anaesthetized mice might be
      partially attributed to the reduced retention of the PA/LPD particles in the
      nasal cavity of the non-anaesthetized mice. Data collected in this study are
      expected to be useful for future anthrax nasal vaccine studies when mice are used
      as a model.

PMID- 16597362
TI  - Effects of enzyme inducers and inhibitors on the pharmacokinetics of intravenous
      ipriflavone in rats.
AB  - In order to find out what types of the hepatic microsomal cytochrome P450 (CYP)
      isozymes are involved in the metabolism of ipriflavone, ipriflavone at a dose of
      20 mg kg(-1) (or 15 mg kg(-1)) was infused in male Sprague-Dawley rats. In rats
      pretreated with SKF 525-A (a non-specific CYP isozyme inhibitor in rats), the
      total body clearance (CL) of ipriflavone was significantly slower (29.9%
      decrease) than that in control rats. This indicates that ipriflavone is
      metabolized via CYP isozymes in rats, hence various enzyme inducers and
      inhibitors were used in in-vitro or in-vivo studies in rats. In rats pretreated
      with 3-methylcholanthrene and phenobarbital (main inducers of CYP1A1/2 and 2B1/2
      in rats, respectively), the CL values were significantly higher (153 and 67.2%
      increases, respectively). In rats pretreated with sulfaphenazole (a main
      inhibitor of CYP2C11 in rats), the CL was significantly slower (22.5% decrease)
      than that in control rats. On addition of furafylline (a main inhibitor of CYP1A2
      in rats), the in-vitro intrinsic clearance for the disappearance of ipriflavone
      was significantly slower (50.8% decrease) than that without furafylline. However,
      the CL values were not significantly different in rats pretreated with
      orphenadrine and isoniazid (a main inducer of CYP2E1 in rats), and quinine and
      troleandomycin (main inhibitors of CYP2D1 and 3A23/2 in rats, respectively)
      compared to controls. These data suggest that ipriflavone could be metabolized
      mainly via CYP1A1/2, 2B1/2 and 2C11 in rats.

PMID- 16597363
TI  - Ethinylestradiol-loaded ultraflexible liposomes: pharmacokinetics and
      pharmacodynamics.
AB  - This study aimed to develop ultraflexible liposomes as an alternative to the oral
      route, which would enhance the bioavailability and reduce the toxicity of
      ethinylestradiol. Ultraflexible liposomes of ethinylestradiol using an optimized
      concentration of surfactants were prepared and characterized in vitro. The effect
      of surfactant type under non-occlusive conditions on transdermal permeability was
      assessed. A histopathological study was performed to assess the action of
      ethinylestradiol on the uterus and ovaries. The pharmacokinetics of free
      ethinylestradiol (following single oral administration and one day of application
      to the skin), ultraflexible liposomal ethinylestradiol and non-flexible liposomal
      ethinylestradiol were studied in female Sprague-Dawley rats. Insignificant
      differences in size between the ultraflexible liposomal formulations containing
      optimized concentrations of different surfactants were observed. Ultraflexible
      liposomes can penetrate through pores much smaller than their own diameter. The
      transdermal permeability of lipophilic surfactant was greater than that of
      hydrophilic surfactant. The release of ethinylestradiol from the proposed
      formulation through rat skin was found to be constant. The histopathological
      study showed that the ultraflexible liposomal transdermal drug delivery system
      for ethinylestradiol provided effective contraception by follicular cell lysis,
      depletion of zona granulosa and ova, and by increasing the uterine mucosal and
      endometrial proliferation. Encapsulation of ethinylestradiol in ultraflexible
      liposomes modified the pharmacodynamics and pharmacokinetics of the contraceptive
      agent, resulting in a marked improvement in bioavailability and optimized
      therapy.

PMID- 16597364
TI  - Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and
      UGT isoforms.
AB  - Resveratrol (trans-resveratrol, trans-3,5,4'-trihydroxystilbene) is a naturally
      occurring stilbene analogue found in high concentrations in red wine. There is
      considerable research interest to determine the therapeutic potential of
      resveratrol, as it has been shown to have tumour inhibitory and antioxidant
      properties. This study was performed to investigate the glucuronidation of
      resveratrol and possible drug interactions via glucuronidation. Two glucuronide
      conjugates, resveratrol 3-O-glucuronide and resveratrol 4'-O-glucuronide, were
      formed by human liver and intestinal microsomes. UGT1A1 and UGT1A9 were
      predominantly responsible for the formation of the 3-O-glucuronide (Km = 149
      microM) and 4'-O-glucuronide (Km = 365 microM), respectively. The glucuronide
      conjugates were formed at higher levels (up to 10-fold) by intestinal rather than
      liver microsomes. Resveratrol was co-incubated with substrates of UGT1A1
      (bilirubin and 7-ethyl-10-hydroxycamptothecin (SN-38)) and UGT1A9 (7
      hydroxytrifluoromethyl coumarin (7-HFC)). No major changes were noted in
      bilirubin glucuronidation in the presence of resveratrol. Resveratrol
      significantly inhibited the glucuronidation of SN-38 (Ki = 6.2 +/- 2.1 microM)
      and 7-HFC (Ki = 0.6 +/- 0.2 microM). Hence, resveratrol has the potential to
      inhibit the glucuronidation of concomitantly administered therapeutic drugs or
      dietary components that are substrates of UGT1A1 and UGT1A9.

PMID- 16597365
TI  - ATP participates in the regulation of microvessel permeability.
AB  - We demonstrated previously that stimulation of the P2Y receptor enhanced the
      macromolecular permeability of cultured endothelial cell monolayers via the
      paracellular pathway. To determine whether the P2Y receptor participates in the
      regulation of permeability in intact microvessels, we have examined the effects
      of exogenous and endogenous ATP on the permeation of the surface tissue of
      perfused rat tail caudal artery using a fluorescein isothiocyanate-dextran (FD-4;
      MW 4400; 1.0 mg mL(-1)). The permeation of FD-4 was assessed by a confocal
      fluorescence imaging system. We found that 2-methylthioadenosine 5'-triphosphate,
      a P2Y receptor agonist, enhanced the fluorescence intensity of FD-4 in the
      surface of the rat caudal artery tissue and that it was inhibited by
      pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist.
      Also, noradrenaline, a sympathetic neurotransmitter, and bradykinin, an
      inflammatory autacoid, enhanced the fluorescence intensity of FD-4 in the surface
      tissue of the rat caudal artery. The enhancement by noradrenaline was
      significantly inhibited by the P2 receptor antagonist. In addition, noradrenaline
      and bradykinin caused the release of ATP, ADP, AMP and adenosine from the
      endothelium of the rat caudal artery. These results indicated that the exogenous
      and endogenous ATP increased the macromolecular permeability of blood capillaries
      via the P2Y receptor. Such purinergic regulation of endothelial permeability may
      function in physiological and pathophysiological conditions.

PMID- 16597366
TI  - Participation of the spinal TRPV1 receptors in formalin-evoked pain transduction:
      a study using a selective TRPV1 antagonist, iodo-resiniferatoxin.
AB  - The involvement of spinal transient receptor potential vanilloid 1 (TRPV1) in
      formalin-evoked pain has remained unclear, because investigation of this kind of
      pain with selective antagonists has not been conducted. The purpose of this study
      is to investigate the participation of spinal TRPV1 in formalin-evoked pain with
      iodo-resiniferatoxin (I-RTX), a potent TRPV1-selective antagonist. I-RTX given
      intrathecally dose-dependently and significantly decreased the number of
      flinching responses in the formalin-evoked 1st and 2nd phase with ID50 values
      (drug dose producing 50% inhibition of response) of 1.0 and 3.8 microg,
      respectively, and concentration-dependently suppressed capsaicin-evoked
      calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) release from rat
      spinal cord slices with an IC50 value (drug concentration producing 50%
      inhibition of response) of 86 nM. Capsazepine, a classical non-selective TRPV1
      antagonist, given intrathecally also inhibited formalin-evoked flinching in both
      the 1st and 2nd phase with ID50s of 420 and 200 microg, respectively, and CGRP-LI
      release from rat spinal cord slices with an IC50 of 7.8 microM. Ratios of in-vivo
      analgesic potencies of I-RTX and capsazepine well reflected their intrinsic in
      vitro activity. These findings suggest that spinal TRPV1 participates in the
      transduction system of formalin-evoked pain.

PMID- 16597367
TI  - Induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural
      compounds from green tea.
AB  - Deposition of amyloid beta-peptide as senile plaques in the brain is one of the
      neuropathological hallmarks of Alzheimer's disease, which is the most prevalent
      progressive neurodegenerative disease leading to dementia. Neutral endopeptidase
      is one of the major beta-amyloid-degrading enzymes in the brain. To examine the
      influence of different polyphenols and other natural products from green tea
      extract (from Camellia sinensis, Theaceae), we used the neuroblastoma cell line
      SK-N-SH and studied the changes in the specific cellular neutral endopeptidase
      activity after long-term treatment with these substances. We have shown that
      caffeine leads to an increase in specific cellular neutral endopeptidase activity
      more than theophylline, theobromine or theanine. We have also shown that the
      combination of epicatechin, epigallocatechin and epigallocatechingallate with
      caffeine, theobromine or theophylline induced cellular neutral endopeptidase
      activity. It is suggested that the enhancement of cellular neutral endopeptidase
      activity by green tea extract and its natural products might be correlated with
      an elevated level of intracellular cyclic adenosine monophosphate.

PMID- 16597368
TI  - Rubiae Radix suppresses the activation of mast cells through the inhibition of
      Syk kinase for anti-allergic activity.
AB  - The effect of extracts from various Oriental medicinal herbs on mast-cell
      mediated allergic reactions was investigated in this study. Of these extracts,
      the medicinal herb Rubiae Radix exhibited the most potent activity in the cells,
      with an IC50 value (concentration necessary to obtain 50% inhibition of the
      response) of approximately 35 +/- 2.1 microg mL(-1), and its inhibition of
      compound-48/80-induced systemic anaphylaxis by 48.6 +/- 8.5% at 300 mg kg(-1) in
      mice. It also inhibited the expression of the pro-inflammatory mediator tumour
      necrosis factor-alpha (TNF-alpha). As for its mechanism of action, Rubiae Radix
      suppressed the activating phosphorylation of Syk, a key enzyme in mast-cell
      signalling processes, and that of Akt in a dose-dependent manner. It also
      inhibited the MAP kinase ERK1/2, which is critical for the production of
      inflammatory cytokines in mast cells, as indicated by the suppression of the
      activating phosphorylation of ERK1/2. These results suggest that Rubiae Radix
      suppresses the activation of mast cells through the inhibition of Syk for anti
      allergic activity.

PMID- 16597369
TI  - Withania somnifera improves bone calcification in calcium-deficient
      ovariectomized rats.
AB  - Osteoporosis, characterized by reduction in bone density, is a significant source
      of mortality among the elderly, particularly in oestrogen-deficient women. We
      studied the effect of Withania somnifera (WS) root extract (ethanolic), which
      contains oestrogen-like withanolides for anti-osteoporotic activity. Female
      Sprague-Dawley rats were either sham operated (n = 12) or ovariectomized (n = 12)
      and treated with WS/vehicle (65 mg kg(-1)), orally for 16 weeks (n = 12). All
      rats were allowed free access to a calcium-deficient diet (0.04% Ca) and
      distilled water. At termination, urinary excretion of calcium (Ca) and phosphorus
      (P) and serum levels of Ca, P and alkaline phosphatase (ALP) were measured. Femur
      and tibia bones were processed for histological (histology), morphological
      (scanning electron microscopy, SEM), biomechanical strength (impact test) and
      mineral composition (ash) analysis. Ovariectomized (OVX) rats showed a
      significant increase in serum ALP levels and urinary Ca and P excretion.
      Histological findings revealed narrowed, and disappearance of, trabeculae with
      widened medullary spaces in the OVX group. Ash analysis showed a reduction in ash
      weight, percent ash, ash Ca, ash P and ash magnesium levels in the OVX group.
      Further, SEM examination revealed metaphyseal bone loss in femurs and impact test
      showed a reduction in biomechanical strength of tibias in OVX rats. WS treatment
      markedly prevented the above changes in OVX rats and thus may be a potential
      agent in the treatment of osteoporosis.

PMID- 16597370
TI  - Induction of cytochrome P450-dependent monooxygenase by extracts of the medicinal
      herb Salvia miltiorrhiza.
AB  - The herbal medicine Salvia miltiorrhiza (Danshen) is currently used for the
      treatment of cardiovascular and cerebrovascular diseases. To assess possible herb
      drug interactions, the effects of the aqueous and ethyl acetate extracts of S.
      miltiorrhiza on cytochrome P450 (CYP) were studied. Oral treatment of C57BL/6J
      mice with the ethyl acetate extract caused a dose-dependent increase in liver
      microsomal 7-methoxyresorufin O-demethylation (MROD) activity. The ethyl acetate
      extract caused an 8-, 2-, 3- and 3-fold increase in hepatic MROD, tolbutamide
      hydroxylation, nifedipine oxidation and warfarin 7-hydroxylation activity,
      respectively. However, the aqueous extract had no effects on any of the
      activities determined. Pharmaceutical product of S. miltiorrhiza extract caused a
      dose-dependent increase in MROD activity without affecting other activity.
      Immunoblot analysis of microsomal proteins showed that ethyl acetate extract
      treatment elevated the protein levels of CYP1A and CYP3A. Tanshinone IIA was the
      main diterpene quinone in S. miltiorrhiza. At the dose corresponding to its
      content in ethyl acetate extract, tanshinone IIA-treatment increased mouse liver
      microsomal MROD activity. These results demonstrated that there were mouse CYP1A,
      CYP2C and CYP3A-inducing agents present in the ethyl acetate extract, but not in
      the aqueous extract, of S. miltiorrhiza. Tanshinone IIA played a role in the
      induction of CYP1A by S. miltiorrhiza. The CYP induction by the ethyl acetate
      extract and pharmaceutical product suggested that possible drug interactions
      between S. miltiorrhiza and CYP substrates should be noticed.

PMID- 16597371
TI  - A polysaccharopeptide complex and a condensed tannin with antioxidant activity
      from dried rose (Rosa rugosa) flowers.
AB  - In this study, the fraction (P) from an aqueous extract of dried rose (Rosa
      rugosa) flowers was obtained by ethanol precipitation. P was chromatographed on
      DEAE-cellulose. The components retained on DEAE-cellulose were eluted with a
      linear gradient of 0-2 M NaCl solution. Two fractions, eluted at concentrations
      of 0.5 M NaCl and 1 M NaCl, respectively, were obtained. These two components
      were designated as P1 and P2, respectively. P1 was further purified using gel
      filtration on Sephadex G-200. P(1) yielded two peaks, and the two components were
      designated as P(1-a) and P(1-b), respectively. P(1-a) was a polysaccharide
      peptide complex, and P(1-b) exhibited chemical properties of a condensed tannin
      as revealed by FTIR and NMR assay of carbohydrate and protein contents and HPLC
      ESI-MS. The molecular masses of P(1-a) and P(1-b) were 150 kDa and 8 kDa,
      respectively. Both P(1-a) and P(1-b) possessed antioxidant activity, with the
      activity of P(1-b) higher than that of P(1-a). This study demonstrated that
      different components from rose flowers exhibited antioxidant activity.

PMID- 16597372
TI  - Activity of the Chinese prescription Hachimi-jio-gan against renal damage in the
      Otsuka Long-Evans Tokushima fatty rat: a model of human type 2 diabetes mellitus.
AB  - Currently, in Japan, approximately 95% of patients with diabetes mellitus have
      non-insulin-dependent (type 2) diabetes mellitus (NIDDM), and diabetic
      nephropathy is a major cause of patients requiring chronic haemodialysis. A
      previous study showed that Hachimi-jio-gan has a protective effect in rats
      subjected to subtotal nephrectomy plus streptozotocin injection, a model of
      insulin-dependent (type 1) diabetic nephropathy. In this study, we used the
      Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of human NIDDM, to
      investigate whether long-term administration of Hachimi-jio-gan affects glycaemic
      control and renal function in NIDDM. Male OLETF rats, aged 22 weeks, were divided
      into 4 groups of 10 and given Hachimi-jio-gan (50, 100 or 200 mg kg(-1) daily)
      orally or no treatment for 32 weeks. Male Long-Evans Tokushima Otsuka (LETO) rats
      (n = 6) were used as non-diabetic normal controls. Hachimi-jio-gan reduced
      hyperglycaemia dose-dependently from 16 weeks of the administration period.
      Urinary protein excretion decreased significantly from an early stage, and
      creatinine clearance levels improved at 32 weeks. In addition, the levels of
      serum glycosylated protein and renal advanced glycation end-products were
      effectively reduced. Hachimi-jio-gan also significantly reduced the levels of
      thiobarbituric acid-reactive substances in renal mitochondria, although it showed
      only a tendency to reduce these in serum. Furthermore, long-term administration
      of Hachimi-jio-gan reduced renal cortical expression of proteins, such as
      transforming growth factor-beta1 (TGF-beta1), fibronectin, inducible nitric oxide
      synthase and cyclooxygenase-2. The 100- and 200-mg kg(-1) daily doses of Hachimi
      jio-gan significantly reduced TGF-beta1 and fibronectin protein expression to
      levels below those of LETO rats. These data suggest that Hachimi-jio-gan may have
      a beneficial effect on the progression of diabetic nephropathy in OLETF rats by
      attenuating glucose toxicity and renal damage.

PMID- 16597373
TI  - Changes in brain biogenic amines and haem biosynthesis and their response to
      combined administration of succimers and Centella asiatica in lead poisoned rats.
AB  - This study was designed to investigate the therapeutic potential of meso 2,3
      dimercaptosuccinic acid (DMSA) and one of its monoesters, monoisoamyl DMSA
      (MiADMSA), individually or when administered in combination with an extract of
      Centella asiatica against experimental lead intoxication in rats. Biochemical
      variables indicative of alterations in the central nervous system and haem
      biosynthesis were investigated to determine the toxicity in male Wistar rats.
      Thirty five rats were exposed to 0.2% lead acetate for 10 weeks, followed by 10
      days of treatment with DMSA and MiADMSA (50 mg kg(-1), i.p., once daily) alone
      and in combination with C. asiatica (200 mg kg(-1), p.o., once daily).
      Biochemical variables indicative of oxidative stress and brain biogenic amines,
      along with lead concentration in blood and brain, were measured. Lead exposure
      caused a significant depletion of blood and brain delta-aminolevulinic acid
      dehydratase (ALAD) activity, an important enzyme of the haem biosynthesis
      pathway, and glutathione (GSH) level. These changes were accompanied by a marked
      increase in reactive oxygen species (ROS) level, thiobarbituric acid reactive
      substances (TBARS), delta-aminolevulinic acid synthase (ALAS) and oxidized
      glutathione (GSSG) activity in blood and brain. Significant depletion of brain
      noradrenaline (norepinephrine, NE), 5-hydroxytryptamine (5-HT), dopamine (DA) and
      acetylcholinesterase (AChE) also were observed following lead exposure. Also seen
      was a significant depletion in brain glutathione peroxidase (GPx), glutathione S
      transferase (GST) and monoamine oxidase activity, as well as blood and brain
      superoxide dismutase (SOD) activity. These biochemical changes were correlated
      with an increased uptake of lead in blood and brain. Combined administration of
      MiADMSA and C. asiatica was most effective in reducing these alterations,
      including biogenic amines, besides reducing body lead burden, compared with
      individual treatment with MiADMSA. Certain other biochemical variables responded
      favourably to combination therapy and monotherapy with MiADMSA. Thus,
      supplementation of C. asiatica during chelation could be recommended for
      achieving optimum effects of chelation therapy.

PMID- 16597374
TI  - Antioxidant properties of propargylamine derivatives: assessment of their ability
      to scavenge peroxynitrite.
AB  - A series of arylpropargylamines, variously substituted in the hydrogen in p
      position and in the propargyl moiety, were studied as potential peroxynitrite
      scavengers. The scavenging activity of these compounds was evaluated through
      peroxynitrite (ONOO-)-mediated oxidation of dichlorofluorescin and linoleic acid
      by measuring the dichlorofluorescein formation and oxygen consumption,
      respectively. Among tested compounds, only 1-phenylpropargylamine (AP3) promoted
      concentration-dependent inhibition of ONOO(-)-induced dichlorofluorescin and
      linoleic acid oxidation with IC50 values of 637 and 63 microM, respectively. The
      AP3 spectral changes in UV-visible absorbance properties in the presence of
      peroxynitrite suggested the formation of a new compound. This was identified by
      gas-chromatograph-mass spectrometer analysis as phenylpropargyl alcohol.
      Structure-activity relationship analysis indicated that the scavenging activity
      of AP3 was due to the aminopropargyl moiety and availability of the nitrogen
      electron pair. This data suggested that AP3 could be considered a lead compound
      for the synthesis of new ONOO- scavenger derivatives.

PMID- 16597375
TI  - Cardiotoxic effects of arsenic trioxide/imatinib mesilate combination in rats.
AB  - Cardiotoxicity is an important consideration in the evaluation of cancer
      chemotherapy, because chemotherapy-induced myocardial damage might be
      irreversible and lethal. This in-vivo study investigated the cardiotoxicity of
      either arsenic trioxide or imatinib mesilate, or a combination of both drugs,
      following repeated administration in male Wistar rats. Both arsenic trioxide and
      imatinib mesilate were administered daily at a dose of 5 mg kg(-1)
      intraperitoneally and 30 mg kg(-1) orally for 10 days, respectively.
      Cardiotoxicity was evaluated by biochemical and histopathological examination 48
      h after the last dose. Treatment with either arsenic or imatinib, or both,
      resulted in significant increases in serum creatine kinase isoenzyme (CK-MB),
      glutathione peroxidase (GPx), lactate dehydrogenase (LDH) and aspartate
      aminotransferase (AST) activity levels. Cardiac tissue of rats treated with
      arsenic showed significant increases in levels of reduced glutathione (GSH)
      content, GPx activity, malondialdehyde (MDA) and total nitrate/nitrite (NOx),
      whereas imatinib treatment significantly increased cardiac GSH content and MDA
      production level and decreased GPx activity level and NOx content. A combination
      of arsenic and imatinib produced significant increases in cardiac GSH content,
      GPx activity and MDA production levels, in addition to a reduction in NOx
      content. Combination arsenic/imatinib treatment extensively increased GPx
      activity and MDA production levels compared with imatinib treatment alone.
      Moreover, rats treated with arsenic or imatinib, or both, showed a significant
      increase in serum bilirubin, creatinine and urea levels. Histopathological
      examination of cardiac tissue of the combination-treated group revealed
      fibroblastic proliferation, myocardial disorganization and myocardial necrosis.
      Liver peroxidative alterations revealed that treatment with either arsenic or
      imatinib, or the two combined, increased levels of reduced-GSH and MDA production
      levels. However, imatinib treatment depleted liver GPx activity level contrary to
      treatment with the combination. Rats treated with arsenic alone or
      arsenic/imatinib combination showed significant elevation in liver NOx. In
      conclusion, both arsenic trioxide and imatinib mesilate might have significant
      cardiotoxicity and cardiac function should be monitored during treatment with
      them alone or in combination, as well as in the presence of pre-existing cardiac
      dysfunction.

PMID- 16597377
TI  - [Heart failure, malnutrition and inflammation. Prevalence and relevant aspects in
      its assessment].
AB  - Heart failure is associated to alterations in the nutritional status that
      contributes to a worse prognosis of the disease. OBJECTIVE: To study protein
      calorie malnutrition (PEM) prevalence, micronutrient deficits and increase of
      inflammatory parameters in patients with cardiac failure (CF). MATERIAL AND
      METHODS: Cross-sectional, observational study in 98 heart failure patients of
      Internal Medicine Service have been evaluated. We have analyzed biomedical,
      anthropometric variables (weight, size, BMI, tricipital fold), search of
      treatments, echocardiogram valuation and determination of albumin, pre-albumin, A
      and E group vitamins, ESR and C-reactive protein. We have defined protein
      malnutrition (PN) as albumin values RESULTS: Average age was 76.6 +/- 7.5. A
      total of 77.7% showed a functional class II-III/IV. Prevalence of PEM was 40%.
      Low albumin and prealbumin was found in 12.8% and 38.3% respectively (p < 0.05).
      Using BMI, 5.3% of patients had malnutrition. Nevertheless, if tricipital fold is
      used, EM was found in the 25.3% of the cases (p < 0.05). Iron iron, vitamin A and
      C-reactive protein levels were different in heart failure patients with PM (p <
      0.05). The percentage of protein malnutrition in patients with LVEF < 45% was
      16.4% versus 5.5% in diastolic dysfunction (p = 0.01). Treatment with ACE
      inhibitors was 42.2%; in this group the malnutrition for any criterion was 13% vs
      26% in the group of patients without ACE-inhibitors (p = 0.08). CONCLUSIONS:
      There is a high prevalence of nutritional and inflammatory disturbances (low in
      diastolic dysfunction) in patients with moderate status of heart failure.
      Treatment with an ACE-inhibitor improves the nutritional parameters.

PMID- 16597376
TI  - [Prevalence and consumption of medication in diabetes mellitus in Madrid (1996
      2002)].
AB  - OBJECTIVES/AIMS: To determine the prevalence of diabetes mellitus treated with
      drugs and the prescription of drugs in diabetes (oral anti-diabetics and insulin)
      in the Community of Madrid between 1996-2002. METHODS: We used the indirect
      method for estimating the rate of prevalence of diabetes based on antidiabetic
      drug in the Madrid Community. We studied the consumption or oral antidiabetics
      (OH) and insulin (IN) in all the Madrid Community Area from 1996 to 2002. To make
      consumption uniform we used the daily doses/1,000 inhabitants/day (DHD). The
      total consumption was obtained using the official billing data and the annual
      population data provided by the "Institute Madrileno de Salud". RESULTS: The
      prevalence of diabetes mellitus increased 62.5% in the period studied, ranging
      from 1.6% in 1996 up to 2.6% in 2002. The DHD of oral drugs increased 87.8% from
      12.2 in 1996 to 23.07 in 2002. The DHD of insulin decreased 28.2% from 3.99 in
      1996 down to 3.11 in 2002. The OH/IN ratio increased 138%, from 3.11 to 7.42 in
      2002. There is a tendency to increase biguanide and sulfonilureas with low risk
      of hypoglycemia. The total cost of insulin and oral medication increase every
      year, the increase of diabetic patients and the cost/DDD of the new drugs are
      factors that increase the total cost of diabetes. CONCLUSIONS: The prevalence of
      diabetes mellitus treated with drugs increased in the Community of Madrid. There
      is a progressive use of oral drugs versus insulin, and a tendency to prescribe
      biguanide, sulfonylureas, especially gliclazide and glimepiride. A tendency to
      substitute insulin with insulin analogues is also seen in the use of insulin. The
      cost of diabetes increases yearly.

PMID- 16597378
TI  - [Application of European Model of Quality in Oncology].
AB  - OBJECTIVES: To assess a Medical Oncology Service using a healthcare setting
      version of the European Foundation for Quality Management (EFQM). To use this
      tool as training, an opportunity for participation and the base for checking the
      strategic planning. MATERIAL AND METHODS: We use the EFQM Model adapted to
      healthcare centers EFQM as the evaluation instrument. It maintains scores and
      weights, only modifying vocabulary and simplifying that not relevant to the
      healthcare setting. Exercise was done with the "proform" system. Its advantage is
      that it uses standard formulas combined with open areas for discussion and
      presentation of ideas. It uses group sessions for agreement. STUDY PERIOD: 2001
      Management. Evaluation was performed in the second term of 2002. RESULTS: 58
      strengths and 37 areas of improvement were identified. These elements were used
      to create a strategic document, which served as the basis for future improvement.
      The score reached was used as an internal reference to monitor service quality
      evolution. CONCLUSIONS: The EFQM model is applicable in a Medical Oncology
      Service, although it would be desirable to have standardized quality indicators
      that permit a more objective and specific evaluation.

PMID- 16597379
TI  - [Treatment of proctalgia fugax with botulinum toxin: results in 5 patients].
AB  - INTRODUCTION: Proctalgia fugax can be defined as transitory but recurrent anal
      pain. Although its etiology remains unknown, an internal anal sphincter spasm
      seems to be the most likely, so that the different treatments focus on reducing
      the pressure of the internal anal sphincter. This study is aimed at evaluating
      the effectiveness of botulinum A toxin in the treatment of proctalgia fugax.
      PATIENTS AND METHODS: Prospective clinical trial of patients with proctalgia
      fugax treated with botulinum A toxin at the Outpatient Clinic attached to the
      Coloproctogy Unit, University Hospital of Elche, from January 1999 to January
      2002. The patients included in the study underwent rectal digital examination,
      anuscopy, rectoscopy, anal manometry and ultrasonography, barium enema and pelvic
      CT scan to rule out any organic cause for anal pain. The treatment consisted of
      25 IU of botulinum A toxin, with a supplementary dose of 50 IU in those patients
      with persistence of anal pain episodes within the next two months. The patients
      were reviewed on the first week, second month, sixth month and first and second
      year. Anal pain was measured by the patients, using a linear analogue scale from
      0 to 10, and continence was assessed at every visit using the Cleveland
      Continence Grading Scale. RESULTS: Five patients were recluted for the study,
      with a predominance of females (4 vs. 1). Mean age was 45 years. Length of
      symptoms prior to the treatment was 13 months (range: 6-18 months). Only one
      female patient required a second dose of botulinum A toxin to handle the anal
      pain. All the patients healed and remained free of pain up to finishing the
      follow-up. There were no local complications. Anal manometry showed an increased
      MRP (mean resting pressure) in comparison to a control group of patients (114
      mmHg vs. 66 mmHg; p < 0.001) that restore to normal values after the treatment
      (75.65 mmHg). As for the MSP (mean squeeze pressure), it showed no difference
      with respect to the control group nor did it vary after the treatment.
      CONCLUSION: Botulinum A toxin offers a high rate of healing with no associate
      morbidity in the treatment of proctalgia fugax.

PMID- 16597380
TI  - [Differential characteristics of primary acute pericarditis and severe
      pericardial effusion without tamponade].
AB  - The aim or our study was to evaluate the main clinical and etiological features
      or primary acute pericarditis with severe pericardial effusion without cardiac
      tamponade. Our experience included 35 patients with this problem diagnosed in the
      last 5 years. Patients with a previous potential etiology for acute pericarditis
      were excluded. The diagnostic protocol identified a specific etiology in 20% of
      patients, the most frequent being idiopathic forms. Patients with severe
      pericardial effusion without cardiac tamponade who had a favourable clinical
      outcome on nonsteroidal antiinflammatory drugs therapy presented a lower
      proportion of specific etiology than those with a poor response to this therapy
      (8% versus 45%; p = 0.03). An exhaustive etiological investigation, including
      diagnostic pericardiocentesis should be reserved for these patients with
      unfavourable response to antiinflammatory drug therapy.

PMID- 16597381
TI  - [Some reflections and findings of a Hypertension [corrected] Unit in Spain].
AB  - The Hypertension Unit, University Hospital San Cecilio of Granada, on fulfilling
      15 years and after the experience acquired in this extended period, wants to
      stress various "facts": 1) the importance of correctly measuring blood pressure,
      avoiding rounding off "numbers" and making three consecutive measurements, taking
      the mean value of the last two; 2) carefully using the concept of "white coat"
      hypertension; the continuous follow-up of these cases and the use of ambulatory
      blood pressure monitoring reveal that they are really hypertensive; 3) using
      those values less than 130/85 mmHg as normality values; 4) the high rate of risk
      factors (obesity, diabetes, hyperuricemia, smoking, etc.) accompanying recently
      diagnosed hypertension; and 5) the need to give an intensive treatment in many
      cases (high doses, greater number of drugs, etc.). The experience of more than
      fifteen years and thousands of patients seen support the ideas included herein.

PMID- 16597382
TI  - [Is it necessary to conduct a urodynamic study in the diagnosis of urinary
      incontinence?].
AB  - Urinary incontinence is a dysfunction that affects 20%-50% of the women in Spain,
      depending on age. Even though it does not involve a prognosis of severity, it
      reduces self-esteem, limits independence and clear deteriorates quality of life.
      The diagnosis is generally made following the international criteria collected in
      the clinical practice guidelines. Even if it is true that the symptoms make it
      possible to suspect the nature of the functional disorder, this is not always
      sufficient or conclusive and there may be errors even in the clearest cases. Even
      so, the need to conduct a urodynamic study in the assessment of women with
      urinary incontinence diagnosed according to the symptoms mentioned continues to
      be debatable and there are no unified and defined criteria in our setting in
      regards to when it is necessary to request urodynamic tests.

PMID- 16597383
TI  - [Management of relapses in smoking dehabituation].
AB  - Due to the recurrent chronic nature of tobacco dependence, health care
      professionals should know the most common reasons for relapses and offer smokers
      who have stopped smoking a preventive treatment. In our setting, some authors
      state that the main causes for which smokers relapse are the negative emotional
      states and social pressures. Among the prevention strategies of relapse are
      providing the patient information, reinforcing his/her decision to stop smoking
      and helping the patient identify and face the danger situations for the
      maintenance of abstinence.

PMID- 16597384
TI  - [Syncope in a 57 year old male].

PMID- 16597385
TI  - [42 year old woman with anterior thoracic mass].

PMID- 16597386
TI  - [General syndrome and skin lesions].

PMID- 16597387
TI  - [Left pleural effusion in patient with heart failure].

PMID- 16597388
TI  - [A rare case of intracardiac massive thrombosis].

PMID- 16597389
TI  - [Leukopenia associated to the use of risperidone: a case report and review of the
      literature].

PMID- 16597390
TI  - ["Lump"?, no thank you].

PMID- 16597391
TI  - [Severe heart failure and anemia].

PMID- 16597392
TI  - [Clinical-therapeutic approach of oral leukoplakia].

PMID- 16597393
TI  - [Viruses].

PMID- 16597394
TI  - [ATP1A2: a key player in familial hemiplegic migraine].

PMID- 16597395
TI  - [LMP-420, a new therapeutic approach for cerebral malaria?].

PMID- 16597396
TI  - [An increase in intracellular free calcium controls the expression of an arginine
      N-methyl-transferase involved in neural determination in amphibian embryo].

PMID- 16597397
TI  - [From cancer to diabetes treatment : the tumor suppressor LKB1 as a new
      pharmacological target].

PMID- 16597398
TI  - [The fibrate-activated PPARalpha/p16INK4A pathway inhibits vascular smooth muscle
      cell proliferation and vascular occlusion].

PMID- 16597399
TI  - [Belatacept, a new original molecule, immunosuppressive, in organ
      transplantation].

PMID- 16597400
TI  - [Is lactate a major energy substrate for neurons?].

PMID- 16597401
TI  - [CD36, a major landmark on the trail of the taste of fat].

PMID- 16597403
TI  - [Histone demethylation isn't what it used to be].

PMID- 16597402
TI  - [Neuronal activity before synaptogenesis: Na+ channels, Ca2+ signalling and
      glutamatergic secretion or how to play the part when some famous actors are
      missing in the scene?].

PMID- 16597404
TI  - [To lose weight, let us make bile].

PMID- 16597406
TI  - [Molecular dating in the genomic era].
AB  - The comparison of DNA and protein sequences of extant species might be
      informative for reconstructing the chronology of evolutionary events on Earth. A
      phylogenetic tree inferred from molecular data directly depicts the evolutionary
      affinities of species and indirectly allows estimating the age of their origin
      and diversification. Molecular dating is achieved by assuming the molecular clock
      hypothesis, i.e., that the rate of change of nucleotide and amino acid sequences
      is on average constant over geological time. If paleontological calibrations are
      available, then absolute divergence times of species can be estimated. However,
      three major difficulties potentially hamper molecular dating : (1) a limited
      sample of genes and organisms, (2) a limited number of fossil references, and (3)
      pervasive variations of molecular evolutionary rates among genomes and species.
      To circumvent these problems, different solutions have been recently proposed.
      Larger data sets are built with more genes and more species sampled through the
      mining of an increasing number of genomes. Moreover, independent key fossils are
      identified to calibrate molecular clocks, and the uncertainty on their age is
      integrated in subsequent analyses. Finally, models of molecular rate variations
      are constructed, and incorporated in the so-called relaxed molecular clock
      approaches. As an illustration of these improvements, we mention that the debated
      age of the animal (bilaterian metazoans) diversification may have occurred
      between 642-761 million years ago (Mya), roughly 100 Ma before the Cambrian
      explosion. Among mammals, the initial diversification of major placental groups
      may have taken place around 100 Mya, well before the Cretaceous/Tertiary boundary
      marking the extinction of dinosaurs.

PMID- 16597407
TI  - [Regulation of energy metabolism by AMPK: a novel therapeutic approach for the
      treatment of metabolic and cardiovascular diseases].
AB  - The 5' AMP-activated protein kinase (AMPK) is a sensor of cellular energy
      homeostasis well conserved in all eukaryotic cells. AMPK is activated by rising
      AMP and falling ATP, either by inhibiting ATP production or by accelerating ATP
      consumption, by a complex mechanism that results in an ultrasensitive response.
      AMPK is a heterotrimeric enzyme complex consisting of a catalytic subunit alpha
      and two regulatory subunits beta and gamma. AMP activates the system by binding
      to the gamma subunit that triggers phosphorylation of the catalytic alpha subunit
      by the upstream kinases LKB1 and CaMKKbeta. Once activated, it switches on
      catabolic pathways (such as fatty acid oxidation and glycolysis) and switches off
      ATP-consuming pathways (such as lipogenesis) both by short-term effect on
      phosphorylation of regulatory proteins and by long-term effect on gene
      expression. Dominant mutations in the regulatory gamma subunit isoforms cause
      hypertrophy of cardiac and skeletal muscle providing a link in human diseases
      caused by defects in energy metabolism. As well as acting at the level of the
      individual cell, the system also regulates food intake and energy expenditure at
      the whole body level, in particular by mediating the effects of adipokines such
      as leptin and adiponectin. Moreover, the AMPK system is one of the probable
      target for the anti-diabetic drug metformin and rosiglitazone. The relationship
      between AMPK activation and beneficial metabolic effects provides the rationale
      for the development of new therapeutic strategies. Thus, pharmacological AMPK
      activation may, through signaling, metabolic and gene expression effects, reduce
      the risk of Type 2 diabetes, metabolic syndrome and cardiac diseases.

PMID- 16597408
TI  - [Low grade gliomas and cerebral plasticity: fundamental and clinical
      implications].
AB  - Post-lesional plasticity (PLP) describes the processes that reorganize cerebral
      connections after an injury. Since Broca's influential contribution and the
      common endorsement of "localisationist" models of brain physiology, it has been
      widely admitted that PLP was limited, not to say impossible in the so-called
      "eloquent areas". However, recent observations associated with the surgical
      treatments of low grade gliomas have called this dogma into question. Indeed,
      more and more evidence suggest that large cerebral resections can be compensated
      so efficiently that no functional deficits can be detected after the surgery. Pre
      and post surgical investigations based on imaging techniques, as well as intra
      surgical investigations involving electrical stimulations, allow to track the
      nature and the temporal characteristics of these compensations. Compensatory
      reactions begin before the operation, in response to the tumoral growth. They
      remain active during and after the surgery. These compensations can involve the
      perilesional adjacent areas, the distant ipsilateral cerebral structures and the
      homologous contra-lateral regions. When considered together these results have
      obvious fundamental and clinical implications. They open new perspectives for
      understanding cerebral dynamics and the process of brain plasticity.

PMID- 16597409
TI  - [Voltage-dependent calcium channels at the heart of pain perception].
AB  - Voltage-dependent calcium channels represent a major pathway of calcium entry
      into neurons, where they participate actively to cell excitability and to the
      molecular processes of synaptic transmission. For that reason, they have been the
      direct or indirect pharmacological targets of analgesics and this long before
      their implication in the physiology of nociception had been demonstrated. These
      last years, the still more refined molecular characterization of these channels
      and their associated regulatory subunits and the demonstration of their
      implication in nociceptive processes indicates that these structures are prime
      pharmacological targets for the management of pain. Herein, we detail the recent
      breakthroughs on calcium channel structure, function and pharmacology, review the
      implication of calcium channels in the transmission of nociception, and evaluate
      their importance as targets for the treatment of pain perception. The search for
      specific inhibitors of voltage-dependent calcium channels appears as a prelude to
      the development of new promising analgesic molecules.

PMID- 16597410
TI  - [Ebola and Marburg viruses: the humans strike back].
AB  - Ebola and Marburg viruses are the causative agents of rapidly progressive
      hemorrhagic fevers with high mortality rates. Pre- or post-exposure treatments
      against the diseases are currently not available for human use. In the field,
      establishment of strict quarantine measures preventing further virus transmission
      are still the only way to fight the infections. However, our knowledge of Ebola
      and Marburg viruses has markedly increased as a result of two recent discoveries
      discussed in this review. Chandran et al. have elucidated the mechanism by which
      Ebola GP is converted to a fusion-active form. Infectivity of Ebola virus was
      shown to be dependent on the cleavage of GP by cellular endosomal proteases,
      cathepsin B and L, thus opening new therapeutic approaches options. As for Jones
      SM et al., they have successfully vaccinated monkeys with recombinant vesicular
      stomatitis virus expressing Ebola or Marburg virus surface glycoprotein GP, a
      promising vaccine approach.

PMID- 16597411
TI  - [Sphingolipids, vehicle for pathogenic agents and cause of genetic diseases].
AB  - Sphingolipids are present in all eukaryotic cells and share a sphingoid base :
      sphingosine. They were first discovered in 1884 and for a long time they were
      thought to participate to membrane structure only. Recently it has been
      established that they are mainly located in particular areas of the membrane
      called rafts which are signalling platforms. It has also been demonstrated that
      sphingolipids are receptors and second messengers. They play a crucial role in
      cellular functioning and are necessary to maintenance and developing of living
      organisms. However due to their receptor properties, they are also gateway for
      penetration of pathogenic agents such as virus (Ebola, HIV) or toxins
      (botulinium, tetanus). These agents first bind to glycosphingolipids or proteins
      mainly located in rafts. The complex so formed is required for the crossing of
      the membrane by the pathogenic agent. Sphingolipids metabolism is regulated by
      numerous enzymes. A failure in the activity of one of them induces an
      accumulation of sphingolipids known as sphingolipidoses. These are genetic
      diseases having severe consequences for the survival of the organism. The precise
      mechanisms of the sphingolipidoses are still mainly unknown which explains why
      few therapeutic strategies are available. These particular properties of lipids
      rafts and sphingolipids explain why a growing number of studies in the medical
      and scientific fields are devoted to them.

PMID- 16597412
TI  - [Endothelin-1, angiotensin II and cancer].
AB  - Endothelin-1 (ET-1) and angiotensin II (AngII), two potent vasoactive peptides
      involved in the regulation of cardiovascular homeostasis, also induce mitogenic
      and pro-angiogenic responses in vitro and in vivo. Both peptides are produced by
      cleavage of inactive precursors by metalloproteases (endothelin-converting enzyme
      and angiotensin-converting enzyme, respectively) and activate two subtypes of
      membrane receptors (ETA-R and ETB-R for ET-1, AT1R and AT2R for AngII) that all
      belong to the superfamily of G-protein coupled receptors. There is increasing
      evidence that ETA-R, ETB-R and AT1R are expressed in a variety of cancer cells
      and tissues, and may play a role on tumor growth, angiogenesis and invasion in
      vivo. This review summarizes the similarities and differences between the ET-1
      and AngII systems with regard to their reported effects on various aspects of
      cancer. In addition to being expressed on vascular endothelium, ET-1 and AngII
      receptors participate in tumor angiogenesis through the production of the
      angiogenic factor VEGF. Furthermore, recent clinical studies indicate that a
      selective ETA-R antagonist has beneficial effects in prostate cancer, suggesting
      that a similar approach using ETB-R and AT1R blockers might be envisioned.
      Experimental data presented here suggest that a combined therapy targeting both
      ET-1 and AngII systems may prove valuable for future treatments of highly
      angiogenic tumors.

PMID- 16597413
TI  - [Cell survival: differences and differentiation].
AB  - The regulatory mechanisms of cell survival and apoptosis are very complex in
      nature, implicating numerous players and signaling pathways not only in the
      decision-making process of surviving (or dying), but as well as in the execution
      of apoptosis itself. The same complex nature applies with regards to anoikis, a
      form of apoptosis that is largely regulated by integrin-mediated, cell
      extracellular matrix interactions. However, cell survival, apoptosis and anoikis
      also happen to implicate further mechanistic distinctions according to the
      specific tissue and/or cell type concerned. Incidentally, recent studies in a
      particular tissue, the human intestinal epithelium, have unearthed yet another
      layer of complexity in the regulation of these three cellular processes, namely
      the implication of differentiation state-specific mechanisms. Although our
      understanding of the molecular underpinnings of this new concept of
      differentiation state-distinct regulation of cell survival, apoptosis and/or
      anoikis is in its infancy, there is already evidence that such principle applies
      as well to cell types other than intestinal epithelial cells. Further studies on
      the differentiation state-specific regulation of these three cellular processes,
      either under normal or physiopathological situations, should prove crucial in
      increasing our understanding of pathologies which implicate a dysregulation of
      apoptosis and/or anoikis - such as cancer.

PMID- 16597414
TI  - [1848: Gregor Mendel, the monk who wanted to be a citizen].
AB  - This article proposes a previously unpublished French translation of a petition,
      in German, addressed by six Augustinian friars to the Constitutional Parliament
      of Vienna in the revolutionary year 1848. The petition states that members of
      religious orders are deprived of civil rights and demands that they be given
      citizenship ; it also contains a bitter attack on the monastic institution. We
      suggest that Mendel was the author of this text, which he signed and actually
      hand-wrote.

PMID- 16597415
TI  - [Antonmarchi, last physician of Napoleon: requiem for a forger. Autopsy report
      published in 1825 is a plagiarism!].

PMID- 16597417
TI  - [Chikungunya virus: a reemerging alphavirus].

PMID- 16597416
TI  - [Terutroban and endothelial TP receptors in atherogenesis].
AB  - Treatment of thrombotic diseases implicates the use of anti-platelet agents, anti
      coagulants and pro-fibrinolytic substances. Amongst the anti-platelet drugs,
      aspirin occupies a unique position. As soon as it became evident that the major
      action of aspirin is indirect blockade, through inhibition of cyclooxygenase
      (COX), of the production of thromboxane A2 (TXA2), a powerful vasoconstrictor and
      platelet activator, research for new anti-thrombotics that interact more
      specifically with the production and/or the action of TXA2 was started.
      Terutroban (S 18886) is a selective antagonist of TP receptors, the receptors for
      TXA2, that are present on platelets and on vascular smooth muscle cells, but also
      on endothelial cells. The role played by the platelet and smooth muscle cell TP
      receptors in thrombotic disease is well known, and preclinical and clinical
      studies with terutroban have illustrated the powerful antithrombotic effects of
      this agent. The implication of endothelial TP receptors in the development of
      atherosclerotic disease has only been examined during the past five years and
      studies with terutroban have been crucial for understanding the role of these
      endothelial receptors in cardiovascular physiopathology. The goal of the present
      review is to discuss the arguments in favour of the hypothesis suggesting that
      activation of endothelial TP receptors, by causing expression of adhesion
      molecules, favours adhesion and infiltration of monocytes/macrophages in the
      arterial wall, thereby stimulating the development of atherosclerosis. The review
      will also highlight the important contribution of the studies performed with
      terutroban in this research area. The triple activity (anti-thrombotic, anti
      vasoconstrictor, anti-atherosclerotic) observed with terutroban in preclinical
      studies, stressed by the first results in clinical development, places terutroban
      as an innovative drug with a unique potential for treatment of cardiovascular
      disorders.

PMID- 16597418
TI  - Aetiology and pathogenesis of cystic ovarian follicles in dairy cattle: a review.
AB  - Cystic ovarian follicles (COF) are an important ovarian dysfunction and a major
      cause of reproductive failure in dairy cattle. Due to the complexity of the
      disorder and the heterogeneity of the clinical signs, a clear definition is
      lacking. A follicle becomes cystic when it fails to ovulate and persists on the
      ovary. Despite an abundance of literature on the subject, the exact pathogenesis
      of COF is unclear. It is generally accepted that disruption of the hypothalamo
      pituitary-gonadal axis, by endogenous and/or exogenous factors, causes cyst
      formation. Secretion of GnRH/LH from the hypothalamus-pituitary is aberrant,
      which is attributed to insensitivity of the hypothalamus-pituitary to the
      positive feedback effect of oestrogens. In addition, several factors can
      influence GnRH/LH release at the hypothalamo-pituitary level. At the ovarian
      level, cellular and molecular changes in the growing follicle may contribute to
      anovulation and cyst formation, but studying follicular changes prior to cyst
      formation remains extremely difficult. Differences in receptor expression between
      COF and dominant follicles may be an indication of the pathways involved in cyst
      formation. The genotypic and phenotypic link of COF with milk yield may be
      attributed to negative energy balance and the associated metabolic and hormonal
      adaptations. Altered metabolite and hormone concentrations may influence follicle
      growth and cyst development, both at the level of the hypothalamus-pituitary and
      the ovarian level.

PMID- 16597419
TI  - Reviewing the low efficiency of protein utilization in heavy preruminant calves-
      a reductionist approach.
AB  - The efficiency of protein utilization for growth in preruminant calves is
      decreasing with increasing body weight. In contrast to calves weighing less than
      100 kg of body weight, heavy preruminant calves do not respond in protein
      retention to an increased intake of indispensable amino acids in dose-response
      studies. The marginal efficiency of protein utilization is low compared with pigs
      and milk-fed lambs at a similar stage of maturity. A reductionist approach was
      taken to perceive the potential mechanisms for the low protein utilization in
      preruminant calves. Neither an imbalance in the dietary protein to energy ratio
      nor a single limiting indispensable amino acid was responsible for the low
      efficiency. Also, amino acids were not specifically used to detoxify ammonia.
      Alternative hypotheses to explain the low efficiency are discussed and result in
      (i) a reduced post-absorptive supply of amino acids: e.g. by fermentation of milk
      in the (premature) rumen or preferential amino acid utilization by specific
      tissues; or (ii) a reduced post-absorptive amino acid utilization: e.g. by
      decreased insulin sensitivity, utilization of amino acids for gluconeogenesis or
      an asynchronous nutrient supply. In conclusion, several mechanisms for the low
      efficiency of protein utilization in heavy preruminant calves were excluded.
      Other physiological processes which are potentially involved remain to be
      studied, because the large potential for improving protein utilization in heavy
      preruminant calves asks for further exploration of their amino acid metabolism.

PMID- 16597420
TI  - Genotoxical, teratological and biochemical effects of anthelmintic drug
      oxfendazole Maximum Residue Limit (MRL) in male and female mice.
AB  - Oxfendazole, methyl-5 (6)-phenylsulfinyl-2-benzimidazole carbamate, is a member
      of the benzimidazole family of anthelmintics. Anthelmintic benzimidazoles are
      widely used in meat producing animals (cattle, sheep and pigs) for control of
      endoparasites. The extensive use of veterinary drugs in food-producing animals
      can cause the presence of small quantities of the drug residues in food. Maximum
      residue limit or "MRL" means the maximum concentration of residue resulting from
      the use of a veterinary medicinal product which may be legally permitted
      recognized as acceptable in food. The FAO/WHO Expert Committee on Food Additives
      (1999) evaluations of toxicological and residue data, reported that oxfendazole
      (MRL) has toxicological hazards on human health. The toxicity of oxfendazole
      (MRL) was tested in male and female mice and their fetuses. Chromosomal
      aberrations, teratological examination and biochemical analysis were the
      parameters used in this study. The results show that oxfendazole MRL induced a
      mutagenic effect in all tested cell types. Also, oxfendazole exhibit
      embryotoxicity including teratogenicity. The biochemical results show that
      oxfendazole induced a disturbance in the different biochemical contents of all
      tested tissues. So, we must increase the attention paid to the potential risk of
      oxfendazole residues in human beings and should stress the need for careful
      control to ensure adherence to the prescribed withdrawal time of this drug.

PMID- 16597421
TI  - Neonatal treatment with naloxone increases the population of Sertoli cells and
      sperm production in adult rats.
AB  - Endogenous opioid peptides play an important role in the ontogenesis of the
      functional and morphological parameters of the seminiferous epithelium. The aim
      of this study was to evaluate the effects of neonatal manipulations with
      naloxone, an opioid antagonist, on the population of Sertoli cells and on sperm
      production in adult rats. Rats were assigned to receive 8 mug per gram of body
      weight twice a day with interval of 8 h of naloxone and they were compared to a
      control group receiving saline. Naloxone groups presented the following findings
      when compared to the control group: increased body weight from the 2nd to the
      27th day; a smaller seminiferous epithelium height, smaller seminiferous tubule
      diameter, increased number of Sertoli cells and daily sperm production per
      testis, increased daily sperm production per gram per testis and increased total
      length of the seminiferous tubule of the treated groups. According to our study,
      the neonatal treatment with naloxone during the critical period of testis
      development was able to change the proliferative dynamics of Sertoli cells by an
      intra and/or extra testicular blockage of opioid receptors, confirming the direct
      relation between the number of Sertoli cells and the number of spermatozoids.

PMID- 16597422
TI  - Effects of a bovine colostrum-supplemented diet on some gut parameters in weaned
      piglets.
AB  - The present study investigated the effects of a bovine colostrum-supplemented
      diet on gut post-weaning adaptation and health in piglets. Thirty-six 21-d-old
      piglets were allocated to one of the three following dietary treatments: sow
      reared (SR), weaned on a control starter diet (WCtrl) or on a starter diet
      supplemented with bovine colostrum (WCol) until slaughter at 28 d or 35 d of age.
      Gastric pH and intestinal bacteriological, structural and functional parameters
      were determined. Compared to WCtrl, the gastric pH was lower (P < 0.05) and the
      duodenal lactobacilli:coliform ratio was higher (P = 0.05) in WCol piglets. The
      relative small intestine weight was 18% (P < 0.05) higher in WCol piglets than in
      SR piglets. Duodenal villous height was lower (P < 0.01) in WCtrl than in SR
      piglets, whereas the value for WCol piglets was intermediate. The weaning
      increased crypt cell proliferation was not affected by bovine colostrum
      supplementation. The mucosal ribosomal capacity was higher (P < 0.05) in W than
      in SR piglets. In conclusion, a diet supplemented with colostrum induced,
      although not always significantly, variations of gut parameters, suggesting that
      globally, colostrum may limit weaning-induced gut structural and microbial
      alterations. The observed effects occurred early and were maintained throughout
      the post-weaning adaptive phase.

PMID- 16597424
TI  - In vivo oxidation of [9-14C] cyclic fatty acids derived from linolenic acid in
      the rat.
AB  - Heating oils and fats may lead to cyclization of polyunsaturated fatty acids, as
      for example linolenic acid. Cyclohexenyl and cyclopentenyl fatty acids are
      subsequently present in some edible oils and these are suspected to induce
      metabolic disorders. In a previous experiment using [1-14C] labeled molecules, we
      published that these cyclic fatty acids are beta oxidized to the same extent as
      linolenic acid, at least for the first cycle of beta oxidation. However, it is
      possible that the presence of a ring could alter the ability of the organism to
      fully oxidize the molecule. In order to test this hypothesis, we assessed the
      oxidative metabolism of cyclic fatty acids carrying a 14C atom at the vicinity of
      the ring. For this purpose, rats were force-fed from 1.1 to 1.3 MBq of a
      representative fraction of dietary cyclohexenyl cyclic fatty acid monomers of [9
      14C] 9-(6-propyl-cyclohex-3-enyl)-non-8-enoic acids and 14CO2 production was
      monitored for 24h. The animals were then necropsied and the radioactivity was
      determined in different tissues. No consistent radioactivity was recovered as
      14CO2 24h after administration of the molecules. Sixty percent of the
      radioactivity was recovered in the urine and 30% in the gastrointestinal tract.
      By combining our previous data on the oxidation of [1-14C] cyclic fatty acids and
      the present results, we suggest that cyclohexenyl fatty acids are first beta
      oxidized in a similar way as linolenic acid and that the remaining molecule
      carrying the ring is detoxified and eliminated in the urine and feces.

PMID- 16597423
TI  - Role of phosphodiesterase in cyclic AMP signaling in cultured rat granulosa
      cells.
AB  - Inactivation of the cyclic nucleotide signal in granulosa cells depends on a
      complex array of cyclic nucleotide phosphodiesterases (PDE). In order to examine
      the role of PDE in cyclic AMP (cAMP) signaling in granulosa cells, the present
      study examined the expression of PDE4D proteins and regulation of cAMP-PDE
      activities in cultured rat granulosa cells. The results of immunoblot analyses
      showed that two predominant PDE4D subtypes of approximately 80 and 70 kDa
      appeared when immature rat granulosa cells were treated with FSH. However, these
      two new subtypes presumed to be PDE4D proteins were not influenced by treatments
      of DETA/NO, cGMP and PKB inhibitor, LY294002. Immature rat granulosa cells
      treated with medium alone displayed low cAMP-PDE activity throughout 48 h of
      culture while those treated with FSH (2 ng.mL-1) showed a marked increase in cAMP
      PDE activity between 6 and 12 h of culture, followed by a decline. The findings
      from the present study indicate that the increased cAMP-PDE activity by FSH is
      mainly related to the changes of PDE4D protein levels. However, the inhibitory
      effects of NO on cAMP accumulation in rat granulosa cells are not via the
      increased cAMP-PDE activity.

PMID- 16597425
TI  - Long term effect of post-weaning rhythm on the body fat and performance of rabbit
      doe.
AB  - Reproductive protocols based on standard (Control: 11 days post-partum) or
      extended rhythm (PW: post-weaning at 27 days post-partum) were compared. Two
      groups of fifty 19-week-old New Zealand White females were inseminated for seven
      consecutive cycles. The kits were weaned at 26 days. On the day of AI, all the
      does were submitted to ultrasound scanning of the perirenal regions to measure
      fat thickness. The fertility rate and several indexes of efficiency were
      calculated. Fat thickness, estimated perirenal fat and live weight were higher in
      PW does. The does submitted to post-weaning rhythm had a higher sexual
      receptivity (P < 0.01), and fertility rate (P < 0.01) whereas litter size and pre
      weaning mortality were not affected. Primiparous Control does showed a
      particularly low fertility rate; the value increased successively but was always
      lower than in PW does. PW rhythm in comparison with the standard one seemed more
      adapted to doe reproductive physiology even if there was a lower production (35.0
      vs. 38.8 rabbit sold/year) and risk of fatness (18% of multiparous does).

PMID- 16597426
TI  - Effect of nursing methods and faeces consumption on the development of the
      bacteroides, lactobacillus and coliform flora in the caecum of the newborn
      rabbits.
AB  - The effect of nursing method and ingestion of maternal faeces on the development
      of the bacteroides, lactobacillus and coliform flora of the caecum in the first
      10 days of life were examined in freely nursed pups having access to maternal
      faeces (Group FF), pups nursed once a day and having access (Group CF), or having
      no access (Group CN) to maternal faeces. Colonisation of the caecum by
      Bacteroides commenced already on day 3 after birth. On day 2 the bacteroides
      counts were below 100, while on day 4 they were already between 100 and 10,000.
      In Group CN, the Bacteroides counts were lower (by 14 to 40%) throughout the 10
      day period studied than in the groups having access to maternal faeces.
      Differences between groups were significant only on days 4 and 6. The average
      number of maternal faecal pellets left behind the doe in Group CN was 3-4
      (between 0.5 and 6.4 per doe). In Groups FF and CF the pellets became smaller,
      crumbled and finally disappeared from the nest box, they were consumed by the
      pups and could be found in their gastric content. The lactobacillus counts
      decreased in all three groups with age, from 6.0 to 3.5 log10 CFU.g-1 (FF), 4.6
      to 2.8 log10 CFU.g-1 (CF) and 5.1 to 3.1 log10 CFU.g-1 (CN), respectively. The
      coliform counts were higher in the first 4 days in FF (5.6 log10 CFU.g-1) than in
      CF (< 2 log10 CFU.g-1) and CN (2-3.6 log10 CFU.g-1) animals. Bacteroides could be
      cultured from the surface of the vulvar labia (max. 1000 colony count) and the
      vagina (max. 190 colony count), so young rabbits could become "infected" by them
      already in the doe's vagina. Thus prevention of ingestion of maternal faeces only
      slightly influenced the development of the bacteroides flora, the faeces left
      behind by the doe did not play an exclusive role in their colonisation.

PMID- 16597427
TI  - Production of butter fat rich in trans10-C18:1 for use in biomedical studies in
      rodents.
AB  - Trans fatty acids are suspected to be detrimental to health, particularly to
      cardiovascular function. Trans fatty acids include a wide range of fatty acids,
      with isomers of C18:1, conjugated and non-conjugated C18:2 as major components. A
      vaccenic acid (trans11-C18:1) + rumenic acid (cis9,trans11-CLA)-rich butter has
      been shown previously to exhibit health beneficial effects, but less is known
      concerning another trans-C18:1 present in hydrogenated vegetable oil-based
      products and sometimes in milk fat, the trans10-isomer. The present experiment
      was conducted to produce butters from milk of variable fatty acid composition for
      use in biomedical studies with rodents, with the overall aim of evaluating the
      specific effect of trans10-C18:1 and trans11-C18:1 + cis9,trans11-CLA on
      cardiovascular function. Milks from lactating dairy cows fed two types of maize
      based diets supplemented (5% of dry matter)--or not--with sunflower oil were
      collected, and used to manufacture butters either rich in trans10-C18:1 (14% of
      total fatty acids, 64.5% of fat content) or rich in trans11-C18:1 + cis9,trans11
      CLA (7.4 and 3.1% of total fatty acids, respectively, 68.5% of fat content), or
      with standard fatty acid composition (70% of fat content). Additionally, total
      saturated fatty acid percentage was reduced by more than one third in the
      enriched butters compared with the standard butter. An understanding of the role
      of nutrition on milk fatty acid composition in cows allows for the production of
      dairy products of variable lipid content and composition for use in biomedical
      studies in animal models and human subjects.

PMID- 16597428
TI  - Demecolcine-induced enucleation of sheep meiotically maturing oocytes.
AB  - The objective of this study was to investigate the possible effect of
      demecolcine, a microtubule-disrupting reagent, on induced enucleation (IE) of
      sheep meiotically maturing oocytes. Immunofluorescent staining with anti-tubulin
      antibodies was used to examine the spindle status of the oocytes. When the
      oocytes with intact germinal vesicles (GV) were cultured in the medium containing
      various concentrations of demecolcine (0.01 to 0.4 microg.mL-1) for 20 to 22 h,
      the spindle microtubule organization and first polar body (PB1) extrusion were
      inhibited by demecolcine in a dose-dependent manner. The highest IE rate (58.1%)
      was from the treatment with 0.04 microg.mL-1 demecolcine. Demecolcine treatment
      applied after germinal vesicle breakdown (GVBD) or at metaphase (M) yielded a PB1
      extrusion rate and IE efficiency similar to the treatment applied at the onset of
      maturation. Analysis by immunofluorescence showed that both nonspindle
      microtubules and spindle microtubules were significantly disorganized by
      demecolcine. Combination treatment with demecolcine and cycloheximide (CHX) or 6
      dimethylaminopurine (6-DMAP) led to single pronuclear formation rather than PB1
      extrusion. When demecolcine-treated oocytes were transferred into demecolcine
      free medium, the ability to extrude PB1 was quickly restored and a 72.1% IE rate
      was obtained following such treatment. These results demonstrate that demecolcine
      can be used as a potential reagent for induced enucleation of sheep meiotically
      maturing oocytes and may greatly facilitate research in nuclear transfer.

PMID- 16597429
TI  - Ethidium bromide is good not only for staining of nucleic acids but also for
      staining of proteins after polyacrylamide gel soaking in trichloroacetic acid
      solution.

PMID- 16597430
TI  - Studies of small molecule interactions with protein phosphatases using biosensor
      technology.
AB  - Reversible protein phosphorylation of serine, threonine, and tyrosine residues by
      protein kinases and phosphatases is important for the regulation of cellular
      signal transduction and controls many cellular functions. Disturbances in this
      regulation have been implicated in a growing number of diseases, making kinases
      and phosphatases useful targets for therapeutic intervention. The suitability of
      surface plasmon resonance (SPR) technology has been widely demonstrated in many
      drug discovery applications. A novel and straightforward methodology is presented
      for analyzing small molecule binding to two serine/threonine phosphatases, PP1
      and PP2B (calcineurin), and to the prototypic tyrosine phosphatase, PTP1B.
      Emphasis was placed on investigating the immobilization conditions of the
      phosphatases by using reducing conditions, inhibitors and metal ions. A
      comparison of inhibitor binding, either to phosphatase (PP2B) alone or in complex
      with the regulatory protein subunit calmodulin, revealed different kinetics. The
      methodology was also used to test inhibitor specificity toward different
      phosphatases. Inhibition of regulatory protein PP-inhibitor-2 binding to PP1 by a
      small molecule inhibitor was demonstrated. This type of information, together
      with data on compound binding that is independent of enzyme activity and in which
      affinities are resolved into kinetic rate constants, may be of great significance
      for the development of highly specific and high-affinity phosphatase inhibitors.

PMID- 16597431
TI  - Characterization of astaxanthin esters in Haematococcus pluvialis by liquid
      chromatography-atmospheric pressure chemical ionization mass spectrometry.
AB  - After first being analyzed by HPLC, 4 free carotenoids, 15 astaxanthin
      monoesters, 12 astaxanthin diesters, and 3 astacin monoesters in Haematococcus
      pluvialis were identified by liquid chromatography-atmospheric pressure chemical
      ionization mass spectrometry (LC-(APCI)MS). Identification of each compound was
      based on the characteristic fragment ions of the positive ion mode, negative ion
      mode, and MS(2). Astaxanthin esters were identified based on the loss of one or
      two fatty acids. In a positive ion mode, astaxanthin monoesters had
      characteristic fragment ions at m/z 597 [M+H-fatty acid](+) and m/z 579 and 561
      that resulted from a continuous loss of water. The relative intensity of m/z 579
      in MS(2) amounted to more than 80% of that of the molecular ion. In astaxanthin
      diesters, the intensity of m/z 561 occasionally was equal to that of m/z 579, but
      in general the former, amounting to 50 to 60% or more of the molecular ion, was
      stronger than the latter, which decreased to 20 to 30% of the molecular ion. In
      addition, a set of compounds with maximum absorbance at 400 nm, detected by high
      performance liquid chromatography-diode array detector (HPLC-DAD), had strong
      characteristic fragment ions at m/z 871 and 593 in the positive ion mode MS(2).
      They were presumed to be linolenic acid or an isomer of omega-6-gamma-linolenic
      acid esters of astacin.

PMID- 16597432
TI  - Mitochondrial UCPs: new insights into regulation and impact.
AB  - Uncoupling proteins (UCPs) are mitochondrial inner membrane proteins sustaining
      an inducible proton conductance. They weaken the proton electrochemical gradient
      built up by the mitochondrial respiratory chain. Brown fat UCP1 sustains a free
      fatty acid (FA)-induced purine nucleotide (PN)-inhibited proton conductance.
      Inhibition of the proton conductance by PN has been considered as a diagnostic of
      UCP activity. However, conflicting results have been obtained in isolated
      mitochondria for UCP homologues (i.e., UCP2, UCP3, plant UCP, and protist UCP)
      where the FFA-activated proton conductance is poorly sensitive to PN under
      resting respiration conditions. Our recent work clearly indicates that the
      membranous coenzyme Q, through its redox state, represents a regulator of the
      inhibition by PN of FFA-activated UCP1 homologues under phosphorylating
      respiration conditions. Several physiological roles of UCPs have been suggested,
      including a control of the cellular energy balance as well as the preventive
      action against oxidative stress. In this paper, we discuss new information
      emerging from comparative proteomics about the impact of UCPs on mitochondrial
      physiology, when recombinant UCP1 is expressed in yeast and when UCP2 is over
      expressed in hepatic mitochondria during steatosis.

PMID- 16597433
TI  - Concurrent excitors limit the extinction of conditioned fear in humans.
AB  - In a human fear conditioning experiment, with on-line expectancy ratings and
      electrodermal responding as indices of fear, two neutral stimuli (pictures of
      geometric shapes) were first established as reliable predictors of an electric
      shock. In the subsequent extinction phase, the two stimuli were repeatedly
      presented in compound, without the shock. The final test phase consisted of
      individual stimulus presentations again, which resulted in a strong return of the
      conditioned responses. This effect was not observed in non-conditioned control
      stimuli. Hence, behavioral effects of extinction seem highly specific to the
      stimulus constellation that has gone through the extinction procedure. We argue
      that pharmacological, behavioral and/or cognitive manipulations that could
      prevent configural processing of stimulus constellations have direct clinical
      potential.

PMID- 16597434
TI  - Purification and characterization of bovine steroid 21-hydroxylase (P450c21)
      efficiently expressed in Escherichia coli.
AB  - Steroid 21-hydroxylase, P450c21, is responsible for the conversion of
      progesterone and 17alpha-hydroxyprogesterone to their 21-hydroxylated
      derivatives. P450c21 has been poorly investigated because of difficulty in
      obtaining sufficient quantities of purified protein. To solve the problem, we
      have attempted to express the bovine P450c21 in Escherichia coli as a stable
      form. The N-terminal membrane anchor and basic regions of P450c21 were replaced
      by the basic region of CYP2C3. The engineered P450c21 was expressed at a level
      higher than 1.2micromol/L culture (>60mg/L) when coexpressed with molecular
      chaperones GroES/GroEL. Utilizing three steps of column chromatography, the
      protein was highly purified to the specific content 16.6nmol/mg (91.2% purity).
      The purified protein is a monomer in the presence of 1% sodium cholate as
      determined by gel filtration analysis, suggesting that this membrane anchor
      truncated form of P450c21 is more soluble than the native form. The purified
      enzyme showed typical substrate-binding difference spectra and 21-hydroxylase
      activities for both progesterone and 17alpha-hydroxyprogesterone. Truncation of
      the membrane anchor increases solubility of P450c21 facilitating expression of
      this protein in E. coli yielding sufficient quantities for both biochemical and
      biophysical studies.

PMID- 16597435
TI  - Losac, a factor X activator from Lonomia obliqua bristle extract: its role in the
      pathophysiological mechanisms and cell survival.
AB  - Contact with the bristles of the caterpillar Lonomia obliqua can cause serious
      hemorrhage. Previously it was reported that a procoagulant protein (Lopap) in the
      bristle extract of L. obliqua increases cell longevity by inhibiting apoptosis.
      In this work, we purified from bristle extract a factor X activator that
      stimulates proliferation of endothelial cells. This protein, named Losac, was
      purified by ion exchange chromatography, followed by gel filtration
      chromatography and reverse-phase HPLC. Losac is a 45-kDa protein that activates
      factor X in a concentration-dependent manner and does not depend on calcium ions.
      In cultures of HUVECs, Losac increased cell proliferation and inhibited the
      apoptosis induced by starvation. HUVECs incubated with Losac (0.58microM for 1h)
      increased release of nitric oxide and tissue-plasminogen activator, which both
      may mediate anti-apoptosis. Losac also increased slightly the decay-accelerating
      factor (DAF=CD55), which protects cells from complement-mediated lysis. On the
      other hand, Losac did not alter the release or expression of von Willebrand
      factor, tissue factor, intercellular adhesion molecule-1, interleukin-8, and
      prostacyclin. These characteristics indicate that Losac, a protein with
      procoagulant activity, also functions as a growth stimulator and an inhibitor of
      cellular death for endothelial cells. Losac may have biotechnological
      applications, including the reduction of cell death and consequently increased
      productivity of animal cell cultures, and the use of hemolymph of L. obliqua for
      this purpose is already being explored. Further study is required to elucidate
      the mechanism for the inhibition of apoptosis by Losac.

PMID- 16597436
TI  - Ubiquinone accumulates in the mitochondria of yeast mutated in the ubiquinone
      binding protein, Qcr8p.
AB  - In Saccharomyces cerevisiae, the trans-membrane helix of Qcr8p, the ubiquinone
      binding protein of complex III, contributes to the Q binding site. In wild-type
      cells, residue 62 of the helix is non-polar (proline). Substitution of proline 62
      with a polar, uncharged residue does not impair the ability of the cells to
      respire, complex III assembly is unaffected, ubiquinone occupancy of the Q
      binding site is unchanged, and mitochondrial ubiquinone levels are in the wild
      type range. Substitution with a +1 charged residue is associated with partial
      respiratory competence, impaired complex III assembly, and loss of cytochrome b.
      Although ubiquinone occupancy of the Q binding site is similar to wild-type,
      total mitochondrial ubiquinone doubled in these mutants. Mutants with a +2
      charged substitution at position 62 are unable to respire. These results suggest
      that the accumulation of ubiquinone in the mitochondria may be a compensatory
      mechanism for impaired electron transport at cytochrome b.

PMID- 16597437
TI  - Increases in preproenkephalin mRNA levels in the Syrian hamster: the influence of
      glucocorticoids is dependent on age and tissue.
AB  - In adult hamsters, basal proenkephalin (Penk) gene expression in adrenals is
      independent of glucocorticoids and glucocorticoid receptor blockade, by RU 486,
      increases striatal preproenkephalin (PPenk) mRNA levels. However, glucocorticoids
      maintain both basal and induced Penk gene expression in rat adrenal (medulla) and
      striatum. This suggests species and tissue-specific differences in Penk gene
      regulation. Since studies show temporal coordination in Penk gene expression in
      developing hamster adrenal and striatum, we tested the hypothesis that increasing
      PPenk mRNA levels are dependent, while basal levels are independent of
      glucocorticoids in developing hamsters. To facilitate this study, we examined the
      influence of glucocorticoids on the temporal increases in developing hamster
      PPenk mRNA observed in adrenals between postnatal days 0 and 4 and in striatum
      between postnatal days 12 and 48. PPenk mRNA levels were determined in hamster
      pups after treatment with increasing doses of metyrapone (an 11beta hydroxylase
      inhibitor) or with the glucocorticoid receptor antagonist RU 486 +/- metyrapone
      between postnatal days 2 and 4. Levels were also determined 36 days after
      hypophysectomy at age 16-17 days. Although plasma glucocorticoid levels and/or
      the influence from glucocorticoids were reduced, only developmental increases in
      PPenk mRNA are influenced by glucocorticoids in hamster adrenals, while basal
      adrenal mRNA levels are unchanged. However, pituitary influence on striatal PPenk
      mRNA levels appears complex and may involve steroid and/or non-steroid factors.
      These results suggest that glucocorticoids regulate hamster Penk gene expression
      via a mechanism that varies with age and tissue and functions during the
      induction of the Penk gene and not to maintain basal gene expression. Possible
      mechanisms and species variation are discussed.

PMID- 16597439
TI  - Vasomotor action of insulin on the rabbit normal cavernous smooth muscle.
AB  - Investigations on the effects of insulin on the normal vasculature have produced
      conflicting results. This study was aimed at establishing the vasomotor actions
      of insulin on normal cavernous smooth muscle. Insulin produced dose-dependent
      (10(-10)-10(-5) M) relaxation of the norepinephrine-precontracted strips of
      cavernosum, and of Bay K8644 [methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4
      2(trifluoromethylphenyl)pyridine-5-carboxylate]-precontracted strips. Endothelial
      denudation or indomethacin (10 microM) pre-treatment significantly reduced these
      insulin-induced relaxations, whereas NG-nitro-L-arginine methyl ester (L-NAME, 5
      mM) did not. Moreover, the pre-treatment of the cavernosum strips with a
      prostacyclin synthesis inhibitor [9,11-diazo-15-deoxy-prostaglandin H2 (U-51605),
      10 microM] significantly reduced insulin-induced response, whereas pretreatment
      with a cyclooxygenase-2 (COX-2) inhibitor (NS-398, 10 microM) did not. In
      addition, responses to insulin were not inhibited by K+ channel blockers, i.e.,
      tetraethylammonium (TEA, 10 mM) or 4-aminopyridine (4-AP, 10 microM). Moreover, L
      type Ca2+ currents were reduced by prostacyclin (2 microM) but not by insulin (10
      microM). We conclude that insulin induces the endothelium-dependent relaxation of
      cavernous smooth muscles and that this relaxation response may emanate from the
      direct inhibition of L-type Ca2+ channels by prostacyclin.

PMID- 16597438
TI  - Anti-nociceptive effect of thalidomide on zymosan-induced experimental articular
      incapacitation.
AB  - The anti-nociceptive effect of thalidomide on zymosan-induced articular knee
      joint incapacitation in rats was investigated. Thalidomide (5-45 mg/kg), given 30
      min before but not 2 h after the intra-articular injection of zymosan, inhibited
      the nociceptive response in a dose-dependent manner. Furthermore, thalidomide
      pretreatment significantly reduced the concentration of tumor necrosis factor
      alpha (TNF-alpha, -68.4%) in the exudate of zymosan-injected joints, but not
      those of interleukin-1beta, interleukin-6, CINC-1 or interleukin-10. The
      expression of TNF-alpha, determined by immunohistochemical staining, in synovial
      tissues obtained from articular joints injected with zymosan was also inhibited
      by thalidomide pretreatment. The anti-nociceptive effect of thalidomide was not
      reversed by the co-administration of an opioid receptor antagonist, naloxone,
      suggesting that endogenous opioids do not mediate the anti-nociceptive effect of
      thalidomide in this model. In conclusion, the anti-nociceptive activity of
      thalidomide in zymosan-induced articular incapacitation is associated with the
      inhibition of TNF-alpha by resident synovial cells.

PMID- 16597440
TI  - Expression of human PQBP-1 in Drosophila impairs long-term memory and induces
      abnormal courtship.
AB  - Frame shift mutations of the polyglutamine binding protein-1 (PQBP1) gene lead to
      total or partial truncation of the C-terminal domain (CTD) and cause mental
      retardation in human patients. Interestingly, normal Drosophila homologue of PQBP
      1 lacks CTD. As a model to analyze the molecular network of PQBP-1 affecting
      intelligence, we generated transgenic flies expressing human PQBP-1 with CTD.
      Pavlovian olfactory conditioning revealed that the transgenic flies showed
      disturbance of long-term memory. In addition, they showed abnormal courtship that
      male flies follow male flies. Abnormal functions of PQBP-1 or its binding partner
      might be linked to these symptoms.

PMID- 16597441
TI  - Ion chromatographic determination of trace iodate, chlorite, chlorate, bromide,
      bromate and nitrite in drinking water using suppressed conductivity detection and
      visible detection.
AB  - An ion chromatography method for the simultaneous determination of trace iodate,
      chlorite, chlorate, bromide, bromate and nitrite in drinking water has been
      developed using an anion-exchange column and the suppressed conductivity
      detector, followed by post-column addition of reagent to enhance visible
      absorbance detection of ions. A high capacity anion exchange Ion Pac9-HC column
      (250 mm x 4 mm I.D.) was used. Eight millimole per liter sodium carbonate was
      used as eluent, an auto-suppression external water mode was selected, 0.5 g/l o
      dianisidine.2HCl (ODA)+4.5 g/l KBr+25% methanel+5.6% nitric acid was used as post
      column reagent. The post-column reaction (PCR) temperature was at 60 degrees C,
      and the visible absorbance detected wavelength at 450 nm. The sample's pH and
      coexist anions had no influence on determination. The method enjoyed a wide
      linear range and a good linear correlation coefficient (r>0.999). The method
      detection limits were between 0.023 and 2.0 microg/l. The average recoveries
      ranged from 87.5 to 110.0%, and the relative standard deviations (RSD) were in
      the range of 1.1-4.6%. The analytical results by the method of post-column
      addition of reagent to enhance visible absorbance detection of anions was
      compared with that of the suppressed conductivity detection, and the former was
      proved to be better in sensitivity and selectivity. The results showed that this
      method was accurate, sensitive and might be good for application and suitable for
      trace analysis at the level of mug/l.

PMID- 16597443
TI  - Analysis of double-stranded DNA by capillary electrophoresis using poly(ethylene
      oxide) in the presence of hexadecyltrimethylammonium bromide.
AB  - The impact of hexadecyltrimethylammonium bromide (CTAB) on the separation of ds
      DNA by capillary electrophoresis in conjunction with laser-induced fluorescence
      (CE-LIF) detection using poly(ethylene oxide) (PEO) solution is described. The
      use of CTAB for improved separation reproducibility and efficiency of DNA has not
      been demonstrated although it is widely used for controlling the magnitude and
      direction of electroosmotic flow in CE. With increasing CTAB concentration, the
      interactions of DNA with ethidium bromide (EtBr) and with the capillary wall
      decrease. For the separation of DNA fragments with the sizes ranging from several
      base pairs (bp) to 2,176 bp, a polymer solution consisting of 0.75% poly(ethylene
      oxide), 100 mM TB buffer (pH 8.0), 25 microg/mL EtBr, and 0.36 microg/mL CTAB is
      proper. Using the PEO solution, we separated a mixture of DNA markers V (pBR
      322/HaeIII digest) and VI (pBR 328/BglI digest and pBR 328/HinfI digest) within 8
      min at -375 V/cm, with the limit of detection of 2.0 ng/mL based on the peak
      height for the 18-bp DNA fragment. The method is highly efficient
      (>10(6)plate/m), repeatable (RSD of the migration times <1.5%), and sensitive. In
      addition, it is convenient to fill a capillary (75 microm in diameter) with such
      a low-viscosity PEO solution by syringe pushing.

PMID- 16597444
TI  - Theoretical calculation of the retention enthalpy effect on the viscous heat
      dissipation band broadening in high performance liquid chromatography columns
      with a fixed wall temperature.
AB  - The problem of the additional band broadening arising from the trans-column
      temperature profile under conditions of significant viscous heat dissipation has
      been extended by including the retention enthalpy effect. This effect can
      significantly aggravate the trans-column migration velocity profile of retained
      species as compared to the already known zero-retention enthalpy case. An
      approximate analytical solution for the accompanying additional band broadening
      could be established. The solution is valid in nearly all practically relevant
      cases and shows how the additional band broadening varies as a function of the
      generated heat, the retention coefficient and the retention enthalpy. Surveying
      all possible HPLC operating conditions, it was found that the inclusion of the
      retention enthalpy effect leads to significantly larger viscous heating plate
      height contributions than those predicted by the zero-retention enthalpy solution
      (up to a factor of 10 or more).

PMID- 16597442
TI  - Comparison of stir bar sorptive extraction and membrane-assisted solvent
      extraction as enrichment techniques for the determination of pesticide and
      benzo[a]pyrene residues in Brazilian sugarcane juice.
AB  - The present work compares two modern and environmentally friendly enrichment
      techniques, stir bar sorptive extraction (SBSE) and membrane-assisted solvent
      extraction (MASE) for the determination of 18 organic contaminant residues in
      Brazilian sugarcane juice. Stir bar sorptive extraction and thermal desorption
      coupled to capillary gas chromatography-mass spectrometry using the selected ion
      monitoring mode [SBSE-TD-GC-MS(SIM)] and membrane-assisted solvent extraction
      combined with large volume injection [MASE-LVI-GC-MS(SIM)] methods were assessed
      taking into account the time of extraction [SBSE (3h) and MASE (30min)], the
      recoveries [SBSE (0.2-55.3%) and MASE (13.6-103.1%)], the repeatability [SBSE
      (0.3-19.2%) and MASE (2.6-18.4%)] and the limits of detection [SBSE (0.002-0.71
      microgL(-1)) and MASE (0.004-0.56 microgL(-1))] of the selected triazine,
      organochlorine and organophosphorus pesticides as well as benzo[a]pyrene in
      sugarcane juice. In general, faster analyses and much better analyte recovery
      results were achieved with MASE, whereas greater sensitivity and repeatability
      were obtained with SBSE. SBSE and MASE procedures were applied to the analysis of
      six sugarcane juice samples from the city Sao Carlos, in the state of Sao Paulo,
      Brazil. A comparison of the results of the pesticide and benzo[a]pyrene residues
      at microgL(-1) level obtained by the two methods showed good agreement.

PMID- 16597445
TI  - High-performance liquid chromatographic determination of chitin in the snow crab,
      Chionoecetes opilio.
AB  - A HPLC method was developed for the determination of glucosamine in crab shells.
      The amount of glucosamine residue can be used to estimate the amount of chitin in
      analyzed material. Crab samples were hydrolysed with 6M HCl at 100 degrees C for
      13 h and the released glucosamine was determined by HPLC using refractive index
      (RI) detection. Separations were performed using an ODS-2 column with an
      isocratic mobile phase consisting of 10% methanol, 90% hexanesulfonate, pH 2.1.
      Glucosamine identification was carried out not only on basis of retention time,
      but also with respect to mass spectra, which were acquired by HPLC-MS.

PMID- 16597446
TI  - Binding behaviour of pyrimethanil-imprinted polymers prepared in the presence of
      polar co-monomers.
AB  - Here, we report the evaluation of the molecular recognition properties of a small
      library of pyrimethanil-imprinted pellicular beads prepared in the presence of
      several co-monomers of decreasing hydrophobicity, namely N
      methacrylamidopiperidine, methylmethacrylate, N-methacrylamidopyrrolidine, N
      vinylpyrrolidone, 2-hydroxyethylmethacrylate, acrylonitrile, N
      methacrylamidomorpholine, and N,N-dimethylacrylamide. The effect of the presence
      of these co-monomers on the molecular recognition properties of the beads were
      studied by eluting the pyrimethanil/Sudan Orange G pair, in the presence of
      acetonitrile/water mobile phases of increasing polarity. The pyrimethanil was
      used to probe the specific interactions due to the presence of binding sites. The
      Sudan Orange G (that is greatly different from the template but with comparable
      hydrophobicity and molecular mass) was instead used to probe the non-specific
      interactions due to the bulk of the polymer. The experimental results show that
      the polymers prepared in the presence of polar co-monomers are characterised by a
      marked increase of the analytes retention if compared with the imprinted polymer
      prepared without these co-monomers. The increase of retention is more pronounced
      for pyrimethanil compared to Sudan Orange G with polymers prepared in the
      presence of the more hydrophilic co-monomers N-vinylpyrrolidone, acrylonitrile
      and N-methacrylamidomorpholine, while N,N-dimethylacrylamide is the only co
      monomer that does not significantly influence the retention of analytes.
      Increasing the amount of water in the mobile phase progressively diminishes this
      effect.

PMID- 16597448
TI  - Aquarium species: deadly invaders.

PMID- 16597447
TI  - Towards an international framework for communication disorders: use of the ICF.
AB  - There has been an interest in the World Health Organization's framework of
      functioning and disability by those in communication disorders since the original
      1980 International Classification of Impairments, Disabilities, and Handicaps
      (ICIDH). In 2001, WHO published the substantially revised International
      Classification of Functioning, Disability, and Health (ICF). This framework is
      gaining in acceptance as a system that would be beneficial for the field and for
      our clients. This article describes the basics of the ICF and how it differs from
      the ICIDH; the possible applications of the ICF to communication disorders; some
      of the work done with the ICF in communication disorders internationally; and the
      benefits to the field from increased interdisciplinary and international
      collaboration using the ICF as a common framework. LEARNING OUTCOMES: As a result
      of this activity the reader will be able to: (1) describe the basics of the ICF,
      (2) describe the applications of the ICF to communication disorders, and (3)
      describe the possible impact upon the field internationally.

PMID- 16597449
TI  - Phenylethynylpyrene-labeled oligonucleotide probes for excimer fluorescence SNP
      analysis of 23S rRNA gene in clarithromycin-resistant Helicobacter pylori
      strains.
AB  - The use of phenylethynylpyrene excimer forming pair in the design of specific
      fluorescent probes for determination of A2144G (A2143G and/or A2143C) mutations
      in 23S rRNA gene of Helicobacter pylori is described. Analysis of fluorescence
      spectra of model duplexes revealed optimal positions of fluorophore residues in
      the probe sequences for maximum efficiency of SNP detection. Application of
      excimer forming probes for analysis of DNA samples isolated from natural
      bacterial strains of H. pylori was demonstrated.

PMID- 16597450
TI  - Isolated numerical skills in posterior cortical atrophy--an fMRI study.
AB  - Posterior cortical atrophy (PCA) is characterized by bilateral parieto-occipito
      temporal atrophy and hypometabolism. Neuropsychological impairments include
      complex visual disturbances, alexia, agraphia, finger agnosia, right-left
      disorientation and dyscalculia. A recent case study reported severe numerical
      deficits with some selectively preserved numerical skills in a patient affected
      by PCA [Delazer, M., Karner, E., Zamarian, L., Donnemiller, E., & Benke, T.
      (2006). Number processing in posterior cortical atrophy--a neuropsycholgical case
      study. Neuropsychologia]. In a functional magnetic resonance imaging (fMRI) study
      brain activation patterns related to these selectively preserved numerical skills
      were analyzed. Recitation of multiplication tables and counting forward were
      contrasted to word recitation in a block design. Contrasts between experimental
      conditions and control condition yielded significant activation of inferior and
      medial temporal structures. Since numerical processing is generally associated
      with parietal activation, it was hypothesized that preserved brain structures
      would compensate for the functional deficits.

PMID- 16597451
TI  - Are representations of unfamiliar faces independent of encoding modality?
AB  - It is well documented that both featural and configural information are important
      in visual face recognition. Less is known, however, about the nature of the
      information underlying haptic face recognition and whether or not this
      information is the same as in vision. In our experiments we found better within
      modal than crossmodal face recognition performance suggesting that face
      representations are largely specific to each modality. Moreover, this cost in
      crossmodal performance was found to be independent of differences in exploratory
      procedures across the modalities during encoding. We found that crossmodal face
      perception was most efficient when configural information of the facial features
      was preserved suggesting that configural information is shared across modalities.
      Our findings suggest that face information is processed in a similar manner
      across vision and touch but that qualitative differences in the nature of the
      information encoded underlies efficient within modal relative to crossmodal
      recognition.

PMID- 16597453
TI  - A model for correcting the fluorescence signal from a free-falling depth
      profiler.
AB  - Measuring chlorophyll fluorescence at five different wavelengths provides the
      discrimination of four phytoplankton groups. Here the problems associated with a
      free-falling depth profiler for phytoplankton discrimination are considered. When
      F0, F, and Fm are determined sequentially in the same measuring cell, then the
      algae inside the cell have a different light history. It depends on their
      different locations in the cell as caused by the induction curve of chlorophyll
      fluorescence. Mathematical algorithms are developed which enable the calculation
      of the concentrations of individual phytoplankton groups from the integral
      fluorescence signal (averaged for 1s) for different velocities of the falling
      probe. The theory requires the knowledge of the fluorescence behaviour of
      phytoplankton in stationary suspensions. The predictions of the model are
      compared with measurements in flowing suspensions containing chlorophyta,
      cyanobacteria, cryptophyta and diatoms. The comparison shows the reliability of
      the algorithms. The application of the algorithms is indispensable for dark
      adapted cells and is less important for light-adapted cells.

PMID- 16597452
TI  - Molecular properties and preclinical pharmacology of JNJ-1250132, a steroidal
      progesterone receptor modulator that inhibits binding of the receptor to DNA in
      vitro.
AB  - Progesterone receptor modulators have diverse potential therapeutic uses,
      including the treatment of endometriosis, uterine fibroids and breast cancer.
      Here we describe the molecular properties and preclinical pharmacology of a new
      steroidal progestin antagonist, JNJ-1250132. The compound is a high affinity
      ligand for the progesterone receptor, possessing cross-reactivity with other
      steroid receptors comparable to that of steroidal antagonists such as
      mifepristone. It inhibits progestin-inducible alkaline phosphatase gene
      expression in T47D human breast cancer cells, and also inhibits their in vitro
      proliferation. It inhibits gestation in rats and progesterone-dependent
      endometrial transformation in rabbits with efficacies comparable to mifepristone.
      Like mifepristone, it is a glucocorticoid antagonist in vivo. In cell-free DNA
      binding assays, the compound inhibits binding of the human progesterone receptor
      to a progesterone response element, and thus is similar to onapristone in this
      regard. In contrast, as judged by proteolytic analysis, JNJ-1250132 induces a
      receptor conformation more similar to that induced by mifepristone, which
      promotes receptor binding to DNA. Therefore, JNJ-1250132 has unique effects on
      the progesterone receptor that may translate into a novel clinical profile.

PMID- 16597454
TI  - Microcystin analysis in single filaments of Planktothrix spp. in laboratory
      cultures and environmental blooms.
AB  - Single filaments of Planktothrix spp. were isolated from laboratory cultures of
      P. agardhii (NIES 595) and P. rubescens (SL 03) and from four freshwater lakes in
      England and Turkey. Filament lengths were measured and microcystins were
      extracted by freeze-thawing and boiling. Microcystin analysis of the isolated
      single filaments was performed by ELISA using antibodies raised against
      microcystin-LR with a minimum detection limit (MDL) of 11 pg filament(-1). In
      some cases a high percentage of the filaments from the environmental samples and
      laboratory cultures were below the MDL of the assay. Based on the filaments with
      detectable microcystin contents, P. agardhii from Bassenthwaite Lake (England)
      had the lowest mean microcystin concentration (0.7 fg microm(-3)), and the
      highest microcystin concentration (2.9 fg microm(-3)) was measured in P.
      rubescens from Iznik Lake (Turkey). We investigated the relationship for
      filaments with microcystin contents above MDL and their biovolume. Relationships
      varied widely although P. agardhii from Bassenthwaite showed a better (positive)
      relationship between filament biovolume and microcystin content than P. rubescens
      from environmental samples. Under culture conditions, P. rubescens showed a good
      relationship between filament biovolume and toxin content.

PMID- 16597456
TI  - Control of the aeration volume in an activated sludge process using supervisory
      control strategies.
AB  - In this paper, a simulation benchmark of a pre-denitrifying activated sludge
      process is utilized in order to evaluate a supervisory aeration volume control
      strategy. The aeration volume control strategy has also been evaluated in a pilot
      plant at Hammarby Sjostad in Stockholm, Sweden. The main idea has been to let the
      dissolved oxygen (DO) concentration in some of the aerated compartments be
      determined by a higher level controller driven by the DO concentration in other
      compartments. In this way, only sensors for measuring the DO concentrations are
      needed for the decision of time varying DO set-points. The high reliability of
      such sensors implies robust input values for the proposed control strategy.
      Moreover, it is known that the respiration rate is affected by the content of
      substrate and nitrogen in the compartments; therefore, the suggested
      manipulations of the DO set-points are indirectly determined by the current load
      into the plant. Compared to constant DO control and a supervisory DO set-point
      control strategy based on ammonium measurements in the last aerobic compartment,
      the suggested aeration volume control strategy could reduce the effluent nitrate
      and ammonium concentrations significantly without increasing the aeration energy.

PMID- 16597455
TI  - Reply to comments on "Derivation of numerical values for the World Health
      Organization guidelines for recreational waters".
AB  - The contribution addressed reveals an optimistic design philosophy likely to
      systematically underestimate risk in epidemiologic studies into the health
      effects of bathing water exposures. The authors seem to recommend that data on
      the 'exposure' measure (i.e. water quality) in such studies should be acquired in
      a similar manner to that used for regulatory sampling. This approach may
      compromise the quality of the epidemiologic investigations undertaken. It may
      result in imprecise estimates of exposure because it ignores the fact that
      regulatory timescales and spatial resolution (even if artificially compressed to
      a bathing day) can mask large spatial and temporal variability in water quality.
      If this variability is ignored by taking some mean value and attributing that to
      all of those exposed in a period at a study location, many bathers may be
      misclassified and the studies may be biased to a 'no-effect' conclusion. A more
      appropriate approach is to maximise the precision of the epidemiologic
      investigations by measurement of individual exposure (or water quality) at the
      place and time of the exposure, as has been done in randomised volunteer studies
      in the UK and Germany. The precise epidemiologic relationships linking 'exposure'
      with 'illness' can then be related to the probability of exposure to particular
      water quality by a 'normal bather' using the known probability distribution of
      the exposure variable (i.e. faecal indicator concentration) in the regulated
      bathing waters. We suggest that any research protocol where poor sampling design
      for water quality assessment is justified because regulatory monitoring is
      equally imprecise may be fundamentally flawed. The rationale for this assessment
      is that the epidemiology is the starting point and evidence-base for 'standards'.
      If precision is not maximised at this stage in the process it compromises the
      credibility of the standards design process. The negative effects of the approach
      advocated in this 'comment' are illustrated using published research findings
      used to derive the figures illustrated in Wymer et al. [2005. Comment on
      derivation of numerical values for the World Health Organization guidelines for
      recreational waters. Water Research 39, 2774-2777].

PMID- 16597457
TI  - Removal of the surfactant sodium dodecylbenzenesulphonate from water by
      simultaneous use of ozone and powdered activated carbon: comparison with systems
      based on O3 and O3/H2O2.
AB  - A study was conducted on the efficacy of the system based on the simultaneous use
      of ozone and powdered activated carbon (PAC) in removing sodium
      dodecylbenzenesulphonate (SDBS) from drinking waters and on the influence of
      operational parameters (PAC dose, ozone dose and presence of radical scavengers
      [HCO3-]) on this process. Results obtained showed that low doses of PAC during
      SDBS ozonation markedly increased the rate of SDBS removal from the medium. These
      results are due to the combined effect of two processes: (i) SDBS adsorption on
      the activated carbon surface and (ii) transformation of the dissolved ozone into
      .OH radicals. At higher ozone and PAC doses, there was a higher rate of SDBS
      removal from the medium. The presence of HCO3- in the medium reduced the SDBS
      removal rate of the O3/PAC system. This finding confirms that the presence of PAC
      during SDBS ozonation favours ozone transformation into .OH radicals. Comparison
      of the O3/PAC system with systems based on the use of O3 or O3/H2O2 showed that
      the efficacy of the O3/PAC system to remove SDBS is much greater than that of the
      traditional oxidation methods. Thus, in the first 5 min of treatment (usual
      hydraulic retention time), the percentage of SDBS removed was 18% and 30% for the
      O3 and O3/H2O2 systems, respectively, compared with 70% for the O3/PAC system.
      SDBS ozonation in surface waters intended for human consumption demonstrated that
      the O3/PAC approach is the most efficacious of the studied systems, considerably
      increasing the SDBS removal rate and also reducing the concentration of dissolved
      organic carbon. Therefore, the results of this study show that the system based
      on O3/PAC is a highly attractive option for the treatment of drinking water.

PMID- 16597458
TI  - Body burden of dioxins and dioxin-like polychlorinated biphenyls in pregnant
      women residing in a contaminated area.
AB  - A large pentachlorophenol (PCP)-manufacturing plant located in southwestern
      Taiwan operated between 1965 and 1982. The present study was conducted to
      ascertain whether an increased body burden of dioxins existed in pregnant women
      living in an area of Tainan city contaminated by chemicals from this plant.
      Twenty-eight pregnant subjects, 21-39 years of age and residing in the study area
      between March and December of 2004 with a mean dwelling time of 6.07+/-6.11
      years, were recruited. Concentrations of polychlorinated dibenzo-p-dioxins,
      dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (PCBs) in
      serum of recruited residents were determined. Pregnant women residing in the
      study area >3 years had significantly higher PCDD (7.48 versus 5.13 pg-toxic
      equivalents [TEQ]/g-lipid) and dioxin-like PCB (6.70 versus 3.74 pg-TEQ/g-lipid)
      values as compared to those residing < or = 3 years. Furthermore, dioxin
      concentrations increased with increasing dwelling time. Statistical analyses
      performed according to demographic characteristics and socioeconomic and dietary
      habits revealed that total TEQ values were significantly associated with fish
      consumption and smoking status. Dioxin congeners with greater degrees of chlorine
      substitution (e.g., HpCDD/F and OCDD/F) partitioned to greater degrees in the
      subjects of this study as compared to subjects in the general Taiwanese
      population. The findings of this study strongly implicate the activity of the PCP
      manufacturing plant in the observed increase in dioxin body burden. Investigation
      of the health consequences of this increased body burden is recommended.

PMID- 16597460
TI  - Increasing trends of total organic carbon concentrations in small forest lakes in
      Finland from 1987 to 2003.
AB  - Trends in total organic carbon (TOC) concentrations over the period 1987-2003
      were studied in 13 small forest lakes. Recovery from acidification (reduced SO(4)
      deposition) and long-term changes in runoff as potential drivers for the trends
      were examined. The results showed that TOC concentrations have increased
      throughout Finland. Ten of the 13 lakes showed a significant increasing TOC trend
      (p<0.05), and included both clear water and humic lakes. The largest annual
      increase in TOC occurred in lakes with the largest average concentrations. The
      magnitude of the TOC trends were not significantly related to the proportion of
      peat soils in the catchment but the catchment size was an important predictor.
      Decreasing SO(4) deposition and improved acid-base status in soil due to the
      recovery from acidification implied an increased mobilisation of organic acids
      and TOC. There was little evidence that the long-term increasing trend in TOC
      concentrations was related to long-term changes in runoff. However, large
      seasonal and inter-annual fluctuations in runoff did appear to affect TOC
      concentrations for a number of years.

PMID- 16597459
TI  - Factors influencing organotin distribution in different marine environmental
      compartments, and their potential health risk.
AB  - Tributyltin (TBT) and triphenyltin (TPT) in different marine environmental
      compartments such as seawater, sediments, and inshore fishes were investigated in
      21 Taiwanese harbors between 2001 and 2004 in order to determine the major
      factors influencing their distribution. The existence of major input sources and
      the limited water exchange rate inside the harbors were indicated by higher TBT
      concentrations in seawater from inner harbor than from outer harbor areas. The
      levels of TBT in sediments were found to be mainly affected by their geographic
      distribution, water exchange rates and shipping activity. No significant
      correlations in TBT concentrations between water, sediment and fish suggested TBT
      accumulation by fish might not result from water and sediment, but from their
      food. TPT were detected in most fish samples, but found in few sediment samples
      and none in seawater, indicating fish could be as a target element for monitoring
      contaminated levels of TPT in the aquatic environment. Mean concentrations of TBT
      in fish muscle higher than tolerable average residue levels (TARLs), and mean
      hazard indices of TBT and TPT higher than 1 suggested consumption of fishes from
      Taiwanese harbor areas might have potential high risk to human health.

PMID- 16597461
TI  - Conventional and toxicogenomic assessment of the acute pulmonary damage induced
      by the instillation of Cardiff PM10 into the rat lung.
AB  - There is strong epidemiological evidence of association between PM10 (particulate
      matter with an aerodynamic diameter less than or equal to 10 microm) and adverse
      health outcomes including death and increased hospital admissions for
      cardiopulmonary conditions. Ambient PM10 surrogates such as diesel exhaust
      particles (DEP), a common component of UK PM10 have been shown to induce lung
      inflammation in both humans and rodents. To date, few studies have reported on
      the toxicological response of UK PM10 in experimental animals. This study
      examines the pulmonary toxicological responses in male Sprague Dawley rats
      following the intratracheal instillation of Cardiff urban PM10. A mild but
      significant change in lung permeability was observed in the lung post
      instillation of a high (10 mg) dose of the whole PM10 as adjudged by increases in
      lung to body weight ratio and total acellular lavage protein. Such effects were
      less marked following instillation of a water-soluble fraction (80% of the total
      mass) but histological examination showed that lung capillaries were swollen in
      size with this treatment. In conclusion, conventional toxicological, histological
      and toxicogenomic studies have indicated that Cardiff PM10 exhibits low
      bioreactivity in the form of mild permeability changes. Differential gene
      expression was observed when the lung was treated with whole PM10, containing
      durable particles, in comparison with the water-soluble fraction of PM10 that was
      devoid of particles. Such changes were linked to different histopathological
      events within the lung.

PMID- 16597462
TI  - Secondary anchor substitutions in an HLA-A*0201-restricted T-cell epitope derived
      from Her-2/neu.
AB  - We investigated analogues of GP2 (IISAVVGIL), an HLA-A*0201-restricted T-cell
      epitope derived from residues 654-662 in the tumor-associated antigen (TAA) Her
      2/neu. One limiting factor of GP2 is its poor affinity for HLA-A*0201.
      Conformational analysis revealed the P5-P7 region in GP2 appears to be linked to
      the stability of P9 side chain interaction with the MHC molecule. To identify
      variants of GP2 with enhanced presentation to HLA-A*0201, we tested V6S, V6T,
      V6Q, G7P, G7F, T6F7, and Q6F7 for their capacity to stabilize cell surface HLA
      A*0201 molecules. Of the mono-substituted variants, V6Q and G7F exhibited
      superior stabilization as compared to GP2. Molecular dynamics simulations suggest
      the improved binding can be attributed to concerted motions in the central and C
      terminal regions of the peptide. These data support the notion that amino acids
      in HLA-A*0201 epitopes may be inter-dependent. Priming HLA-A*0201 transgenic mice
      with G7F-loaded syngeneic dendritic cells stimulated mouse T cells to produce a
      higher level of INFgamma than mice immunized with GP2.

PMID- 16597463
TI  - Molecular cloning, expression of a big defensin gene from bay scallop Argopecten
      irradians and the antimicrobial activity of its recombinant protein.
AB  - Antimicrobial peptides are important components of the host innate immune
      responses by exerting broad-spectrum microbicidal activity against pathogenic
      microbes. The first mollusk big defensin (designated AiBD) cDNA was cloned from
      bay scallop Argopecten irradians by expressed sequence tag (EST) and rapid
      amplification of cDNA ends (RACE) techniques. The scallop AiBD consisted of 531
      nucleotides with a canonical polyadenylation signal sequence AATAAA and a poly(A)
      tail, encoding a polypeptide of 122 amino acids. The high similarity of AiBD
      deduced amino acid sequence with big defensin from Tachypleus tridentatus and
      Branchiostoma belcheri tsingtaunese indicated that AiBD should be a member of big
      defensin family. The expression of AiBD in various tissues was measured by using
      Northern blotting analysis. mRNA transcripts of AiBD could be detected in
      haemocytes of unchallenged scallops. The temporal expression of AiBD in
      haemolymph after Vibrio anguilarum challenge was recorded by quantitative real
      time PCR. The relative expression level of AiBD in haemolymph was up-regulated
      evenly in the first 8 h, followed by a drastic increase, and increased 131.1-fold
      at 32 h post-injection. These results indicated that AiBD could be induced by
      bacterial challenge, and it should participate in the immune responses of A.
      irradians. Biological activity assay revealed that recombinant AiBD could inhibit
      the growth of both Gram-positive and Gram-negative bacteria, and also showed
      strong fungicidal activity towards the expression host. Recombinant expression of
      AiBD made it possible to further characterize its functions involved in immune
      responses, and also provided a potential therapeutic agent for disease control in
      aquaculture.

PMID- 16597464
TI  - Identification of IRF-8 and IRF-1 target genes in activated macrophages.
AB  - Interferon regulatory factor 1 (IRF-1) and IRF-8, also known as interferon
      consensus sequence binding protein (ICSBP), are important regulators of
      macrophage differentiation and function. These factors exert their activities
      through the formation of heterocomplexes. As such, they are coactivators of
      various interferon-inducible genes in macrophages. To gain better insights into
      the involvement of these two transcription factors in the onset of the innate
      immune response and to identify their regulatory network in activated
      macrophages, DNA microarray was employed. Changes in the expression profile were
      analyzed in peritoneal macrophages from wild type mice and compared to IRF-1 and
      IRF-8 null mice, before and following 4 h exposure to IFN-gamma and LPS. The
      expression pattern of 265 genes was significantly changed (up/down) in peritoneal
      macrophages extracted from wild type mice following treatment with IFN-gamma and
      LPS, while no changes in the expression levels of these genes were observed in
      samples of the same cell-type from both IRF-1 and IRF-8 null mice. Among these
      putative target genes, numerous genes are involved in macrophage activity during
      inflammation. The expression profile of 10 of them was further examined by
      quantitative RT-PCR. In addition, the promoter regions of three of the identified
      genes were analyzed by reporter gene assay for the ability to respond to IRF-1
      and IRF-8. Together, our results suggest that both IRF-1 and IRF-8 are involved
      in the transcriptional regulation of these genes. We therefore suggest a broader
      role for IRF-1 and IRF-8 in macrophages differentiation and maturation, being
      important inflammatory mediators.

PMID- 16597465
TI  - Differential partitioning and trafficking of GM gangliosides and cholesterol-rich
      lipid rafts in thymic and splenic CD4 T cells.
AB  - The GM gangliosides and cholesterol components of plasma membrane lipid rafts
      play an important role in the recruitment and signaling of protein receptors in
      eukaryotic cells. Herein, we have analyzed at the single-cell level the
      partitioning and intracellular trafficking of GM gangliosides and cholesterol in
      quiescent (CD4+CD69-) and CD3-activated (CD4+CD69+) thymic and splenic T cells.
      First, regardless the gender and the quiescent or activated status of T cells,
      the GM and cholesterol content in cytosol and plasma membrane as well as the
      expression levels of GM synthase, Sphingomyelin phosphodiestarase 2 and HMG Co-A
      reductase genes involved in GM and cholesterol synthesis were constantly lower in
      CD4 thymocytes than in CD4 splenocytes. Second, we detected variations in the
      balance between GM and cholesterol in plasma membrane depending on aging, and
      found that deprivation of cellular cholesterol does not necessarily affect the GM
      content in both quiescent CD4 thymocytes and splenocytes. Third, CD3 stimulation
      up-regulated the GM and little if any the cholesterol content in both thymic and
      splenic CD4 T cells, suggesting a cross talk between the CD3 signaling and GM but
      not cholesterol biosynthesis pathway. Fourth, partitioning and trafficking of GM
      to the plasma membrane depended on the transport of ceramide precursors from
      endoplasmic reticulum to Golgi network, as well as on the synthesis,
      glycosylation and vesicular assembly in trans-Golgi, and less on the cytoskeleton
      architecture in both quiescent and activated CD4 thymic and splenic T cells.
      Together, these findings suggest that the differential partitioning and
      intracellular trafficking of GM and cholesterol in thymic and splenic CD4 T cells
      may account for the stage of functional maturation.

PMID- 16597466
TI  - Detection of yellow head virus in shrimp by loop-mediated isothermal
      amplification (LAMP).
AB  - Reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was
      developed for detecting the structural glycoprotein gene of yellow head virus
      (YHV). The RT-LAMP assay is a novel method of gene amplification that amplifies
      nucleic acid with high specificity, sensitivity and rapidity under isothermal
      conditions with a set of four specially designed primers that recognize six
      distinct sequences of the target. The whole procedure is very simple and rapid,
      and reaction time and temperatures were optimized for 60 min at 65 degrees C,
      respectively. Detection of gene amplification could be accomplished by agarose
      gel electrophoresis. The standardized RT-LAMP procedure was used to detect YHV in
      the heart and gill from infected shrimp. Thus, the RT-LAMP assay is extremely
      rapid, cost-effective, sensitive and specific and has potential usefulness for
      rapid diagnosis for YHV detection in shrimp.

PMID- 16597467
TI  - 2-Cys Peroxiredoxin TPx-1 is involved in gametocyte development in Plasmodium
      berghei.
AB  - Peroxiredoxins (Prxs) constitute a ubiquitous family of antioxidant enzymes
      involved in diverse cellular functions including cell proliferation and
      differentiation. To investigate the physiologic role of typical 2-Cys Prx in
      malaria parasites (TPx-1), we disrupted this gene in the rodent malaria parasite
      Plasmodium berghei (pbtpx-1). The gene-disrupted parasite (Prx KO) developed
      normally in mouse erythrocytes and multiplied at a rate similar to that of the
      parent strain (WT) during the experimental period. The normal growth rate was not
      altered after 10 passages, and the level of 8-hydroxy-2'-deoxyguanosine, which
      accumulates in the parasite genome during the cell cycle, was similar between Prx
      KO and WT. These results suggest that TPx-1 does not prevent parasite DNA
      oxidation, in contrast to mammalian Prx, and that it is not essential for asexual
      parasite growth in mouse erythrocytes. However, Prx KO produced up to 60% fewer
      gametocytes, sexual-stage parasites involved in the transition between the
      mammalian host and the mosquito, than WT did. The peak of gametocytemia was also
      delayed; however, the male/female ratio of gametocytes and the exflagellation
      activity of male gametocytes were normal. These results suggest that TPx-1 is
      required for normal gametocyte development but does not affect the male/female
      gametocyte ratio or male gametogenesis. Although the mechanism by which PbTPx-1
      contributes to gametocyte development remains unknown, these findings suggest,
      for the first time, the involvement of Prx in the sexual development of the
      malaria parasite.

PMID- 16597468
TI  - Leishmania donovani singly deficient in HGPRT, APRT or XPRT are viable in vitro
      and within mammalian macrophages.
AB  - Leishmania species express three phosphoribosyltransferase enzymes, hypoxanthine
      guanine phosphoribosyltransferase (HGPRT), adenine phosphoribosyltransferase
      (APRT), and xanthine phosphoribosyltransferase (XPRT), which enable this genus to
      acquire purine nutrients from their hosts. To test whether any of these enzymes
      is essential for viability, transformation into amastigotes, and infectivity and
      proliferation within mammalian macrophages, Deltahgprt, Deltaaprt, and Deltaxprt
      null mutants were created by targeted gene replacement within a virulent
      background of Leishmania donovani. Each of the three knockout strains was viable
      as promastigotes and axenic amastigotes and capable of maintaining an infection
      in bone marrow-derived murine macrophages. These data support the hypothesis that
      none of the three phosphoribosyltransferases is essential for purine salvage or
      viability by itself and that purine salvage occurs through multiple anabolic
      routes in both parasite life cycle stages. In addition these studies revealed the
      presence of an adenine aminohydrolase enzyme in L. donovani axenic amastigotes,
      an activity previously thought to be restricted to promastigotes.

PMID- 16597469
TI  - The A/T-specific DNA alkylating agent adozelesin inhibits Plasmodium falciparum
      growth in vitro and protects mice against Plasmodium chabaudi adami infection.
AB  - There is an urgent need for new anti-malarial drugs to combat the resurgence of
      resistance to current therapies. To exploit the A/T richness of malaria DNA as a
      potential target for anti-malarial drugs we tested an A/T-specific DNA synthesis
      inhibitor, adozelesin, for activity against Plasmodium falciparum in vitro and
      Plasmodium chabaudi adami in mice. Adozelesin is a DNA alkylating agent that
      exhibits specificity for the motif A/T, A/T and A. In P. falciparum 3D7 cultures,
      adozelesin acts as a powerful inhibitor of parasite growth (IC(50) of 70 pM) and
      is equally potent at killing the drug-resistant strains FCR3 and 7G8. Using a
      real-time PCR assay, we show that treatment with adozelesin in vitro results in
      damage of P. falciparum genomic DNA. In synchronized cultures, adozelesin
      exhibits a concentration-dependent effect on parasitemia and on the development
      of parasites through the asexual cycle. In asynchronous cultures, parasites
      arrest at all stages of the asexual cycle suggesting that adozelesin exerts other
      anti-parasitic effects in addition to inhibiting DNA replication. These anti
      parasite effects are irreversible since cultures exposed to adozelesin for more
      than 6h fail to recover upon removal of the drug. Furthermore, adozelesin is very
      effective at suppressing malaria infection in vivo; growth of P. c. adami DK in
      mice was highly impaired by a single injection of adozelesin (25 microg/kg) at 4
      days post-infection. These results demonstrate that adozelesin irreversibly
      blocks parasite growth in vitro and suppresses parasite infection in vivo,
      suggesting that A/T-specific DNA damaging agents represent a new class of
      compounds with potential as anti-malarials.

PMID- 16597470
TI  - A prospective study of the effect of Neospora caninum and BVDV infections on
      bovine abortions in a dairy herd in Arequipa, Peru.
AB  - We used a prospective seroepidemiological approach to investigate endemic
      abortion in a dairy herd in Arequipa, Peru, and its association with Neospora
      caninum and bovine viral-diarrhoea virus (BVDV) infections. Between January 2002
      and March 2004, 1094 pregnancies were confirmed in 538 cows. Of these, 137
      pregnancies (13%) in 121 cows ended in abortion. The serological status to N.
      caninum was assessed using a single serological screening, whereas BVDV status
      was assessed at the herd level through consecutive samplings of young stock. Cox
      proportional-hazards models were used to estimate the effect of N. caninum and
      BVDV on the hazard of early (between day 42 and day 100 in gestation), and late
      (after day 100) abortions, respectively. Serological status to N. caninum was
      included as a dichotomous variable, and the effect of BVDV estimated at the herd
      level, as a time-dependent seasonal effect. Because data from repeated
      pregnancies were included, we considered possible lack of independence between
      observations and included frailty effects into the models. Our models also
      considered the possible confounding by parity and animal origin. Only multiparity
      was associated with the hazard of early abortion (HR=2.8 compared to nulliparous
      heifers). N. caninum seropositivity significantly affected the hazard of late
      abortion, but interacted with parity. The HRs for Neospora-positive animals were
      6.4, 3.7 and 1.9, respectively, for nulliparous heifers, first-lactation cows and
      multiparous cows. Evidence of BVDV circulating (or not) among the young stock was
      not associated with abortions, but few cows in this herd were susceptible to
      incident infection.

PMID- 16597471
TI  - Crystals of sarcoplasmic reticulum Ca(2+)-ATPase.
AB  - High-resolution structures of the Ca(2+)-ATPase have over the last 5 years added
      a structural dimension to our understanding of the function of this integral
      membrane protein. The Ca(2+)-ATPase is now by far the membrane protein where the
      most functionally different conformations have been described in precise
      structural detail. Here, we review our experience from solving Ca(2+)-ATPase
      structures: a purification scheme involving minimum handling of the protein to
      preserve natural and essential lipids, a rational approach to screening for
      crystals based on a limited number of polyethyleneglycols and many different
      salts, improving crystal quality using additives, collecting the data and finally
      solving the structures. We argue that certain of the lessons learned in the
      present study are very likely to be useful for crystallisation of eukaryotic
      membrane proteins in general.

PMID- 16597472
TI  - UK health policy and 'underage' smokers: the case for smoking cessation services.
AB  - The UK government's White Paper titled 'Smoking Kills' set explicit targets for
      reductions in the prevalence of smoking. As well as targets for the population as
      a whole, specific targets were set for sub-groups in the population: children
      were identified as one such sub-group. Following the publication of the White
      Paper, smoking cessation services were established nationwide as part of the
      strategy to meet the targets. Considerable resources have been put into these
      smoking cessation services and evaluations of the service tend to conclude that
      they are relatively successful and cost effective in terms of getting people to
      quit smoking. However, this article argues that one group of smokers has been
      marginalised in terms of access to the service. The evidence indicates that
      'underage' smokers - those aged less than 16 years - have not had the level of
      access to smoking cessation services that is warranted in terms of the prevalence
      of smoking among children, in terms of their apparent willingness to use such
      services and in terms of the particular value of quitting smoking while still so
      young. This article explores the potential for underage smokers to benefit from
      smoking cessation services and considers the possibilities for widening access to
      the cessation services to 11-15 years old.

PMID- 16597473
TI  - Response to "The common drug review: a NICE start for Canada?".

PMID- 16597474
TI  - Phase II study of pegylated liposomal doxorubicin HCl (Caelyx) in combination
      with cyclophosphamide and vincristine as second-line treatment of patients with
      small cell lung cancer.
AB  - BACKGROUND: Despite chemotherapy and radiotherapy for small cell lung cancer
      (SCLC), most patients die within 2 years. Response rates for second-line
      chemotherapy are 15-25%, with a median survival of 5 months. Caelyx, a pegylated
      liposomal formulation of doxorubicin, may be better tolerated and has activity in
      SCLC. PATIENTS AND METHODS: Thirty-two patients were enrolled in a phase II study
      of intravenous Caelyx (35 mg/m2), cyclophosphamide (750 mg/m2) and vincristine
      (1.2 mg/m2) every 21 days as second-line therapy in SCLC for up to six cycles.
      RESULTS: Thirty patients were evaluable for response, with a response rate of
      10%. Another two had an unconfirmed response. Stable disease (SD) for >or=2
      cycles was seen in an additional 53%. Grade 3 or 4 non-hematologic toxicity was
      seen in 17 (55%) patients (26 [22%] cycles) and included fatigue, mucositis,
      plantar-palmar erythrodysesthesia, rash and neuropathy. Twelve patients required
      transfusions. All patients on study have now expired, with a median survival of
      28 weeks (7 months). For patients with SD or partial response, median time to
      progression was 15 weeks. CONCLUSION: The combination of Caelyx, cyclophosphamide
      and vincristine, despite cyclophosphamide and Caelyx dose reductions, has modest
      activity in relapsed SCLC with acceptable toxicity.

PMID- 16597475
TI  - A conserved tyrosine residue of Saccharomyces cerevisiae leukotriene A4 hydrolase
      stabilizes the transition state of the peptidase activity.
AB  - Saccharomyces cerevisiae leukotriene A4 hydrolase (LTA4H) is a bifunctional
      aminopeptidase/epoxide hydrolase and a member of the M1 family of
      metallopeptidases. In order to obtain a more thorough understanding of the
      aminopeptidase activity of the enzyme, two conserved tyrosine residues, Tyr244
      and Tyr456, were altered to phenylalanine and the mutant proteins characterized
      by determining KM and kcat for various amino acid beta-naphthylamide substrates.
      While mutation of Tyr456 exhibited minimal effect on catalysis, mutation of
      Tyr244 caused an overall 25-100-fold reduction in catalytic activity for all
      substrates tested. Furthermore, LTA4H Y244F exhibited a 40-fold decrease in
      affinity for RB-3014, a transition state analog inhibitor, implicating Tyr244 in
      transition state stabilization.

PMID- 16597476
TI  - Haplotypes in the urotensin II gene and urotensin II receptor gene are associated
      with insulin resistance and impaired glucose tolerance.
AB  - We studied single nucleotide polymorphisms (SNPs) and haplotypes in the urotensin
      II (UTS2) and urotensin-II receptor gene (UTS2R) in Hong Kong Chinese (224
      hypertensive and 306 normotensive unrelated subjects) and their relation to
      hypertension and the metabolic syndrome. For UTS2, the GGT haplotype (-605G, 143G
      and 3836T) was associated with higher plasma level of U-II and insulin, and
      higher homeostasis model assessment of insulin resistance index and beta-cell
      function. For UTS2R, the AC haplotype (-11640A and -8515C) was associated with
      higher 2 h plasma glucose after a 75 g oral glucose load. Therefore, U-II and its
      receptor may play a role in insulin resistance.

PMID- 16597477
TI  - The lesser evil: bad jobs or unemployment? A survey of mid-aged Australians.
AB  - Paid work is related to health in complex ways, posing both risks and benefits.
      Unemployment is associated with poor health, but some jobs may still be worse
      than no job at all. This research investigates that possibility. We used cross
      sectional survey data from Australians aged 40-44 (N = 2497). Health measures
      were depression, physical health, self-rated health, and general practitioner
      visits. Employees were classified according to their job quality (strain,
      perceived job insecurity and marketability). Employee health was compared to
      people who were unemployed, and to people who were not in the labour force. We
      found that unemployed people reported worse health when compared to all
      employees. However, distinguishing in terms of employee's job quality revealed a
      more complex pattern. Poor quality jobs (characterized by insecurity, low
      marketability and job strain) were associated with worse health when compared to
      jobs with fewer or no stressors. Furthermore, people in jobs with three or more
      of the psychosocial stressors report health that is no better than the
      unemployed. In conclusion, paid work confers health benefits, but poor quality
      jobs which combine several psychosocial stressors could be as bad for health as
      being unemployed. Thus, workplace and industrial relations policies that diminish
      worker autonomy and security may generate short-term economic gains, but place
      longer-term burdens on the health of employees and the health-care system.

PMID- 16597479
TI  - Adjustment to cancer in the 8 years following diagnosis: a longitudinal study
      comparing cancer survivors with healthy individuals.
AB  - This longitudinal study examined the long-term impact of a diagnosis of cancer on
      physical and psychological functioning, by comparing 8-year cancer survivors (n =
      206) to a randomly selected sample of similar-aged references without cancer (n =
      120) in the Netherlands. Comparisons were made at three fixed points in time: 3
      months (T1), 15 months (T2), and 8 years (T3) after diagnosis. The results showed
      that, at 8 years after diagnosis, cancer survivors and references do not differ
      significantly in the level of depressive symptoms, anxiety, life satisfaction,
      self-esteem, social support, and marital satisfaction. However, survivors
      reported more physical symptoms, and those with a recurrence of cancer also
      reported more limitations in household and social activities. Most improvements
      in functioning were found in the year following diagnosis. Intriguingly, we found
      no evidence that cancer survivors experienced more positive changes in the self,
      relationships, or life in general than references, even though many cancer
      survivors attributed these changes to the cancer experience. In the discussion,
      we address the role of finding positive meaning in the process of adjustment to
      cancer.

PMID- 16597478
TI  - What explains the association between neighborhood-level income inequality and
      the risk of fatal overdose in New York City?
AB  - Accidental drug overdose is a substantial cause of mortality for drug users.
      Using a multilevel case-control study we previously have shown that neighborhood
      level income inequality may be an important determinant of overdose death
      independent of individual-level factors. Here we hypothesized that the level of
      environmental disorder, the level of police activity, and the quality of the
      built environment in a neighborhood mediate this association. Data from the New
      York City (NYC) Mayor's Management Report, the NYC Police Department, and the NYC
      Housing and Vacancy Survey were used to define constructs for the level of
      environmental disorder, the level of police activity and the quality of the built
      environment, respectively. In multivariable models the odds of death due to drug
      overdose in neighborhoods in the top decile of income inequality compared to the
      most equitable neighborhoods decreased from 1.63 to 1.12 when adjusting for the
      three potential mediators. Path analyses show that the association between income
      inequality and the rate of drug overdose mortality was primarily explained by an
      indirect effect through the level of environmental disorder and the quality of
      the built environment in a neighborhood. Implications of these findings for the
      reduction of drug overdose mortality associated with the distribution of income
      are discussed.

PMID- 16597481
TI  - A reference basic life support provider course for Europe.
AB  - BACKGROUND: Good scientific evidence is scarce in relation to the effectiveness
      of different methods of teaching basic life support (BLS) to the general public.
      In order to test new courses or methods a reference course is needed as a
      comparative standard. OBJECTIVE: To propose a reference BLS provider course that
      can be used as a comparator when testing new courses or teaching methods.
      METHODS: All national resuscitation councils that are represented in the European
      Resuscitation Council (ERC) were sent a questionnaire about the BLS provider
      courses run by them or under their auspices. RESULTS: Sixteen national
      resuscitation councils responded to the enquiry. Their responses regarding
      organisation, structure, content and methods of the courses were found to be
      remarkably consistent between European countries. Few issues had a high variance.
      CONCLUSIONS: Based on the responses received, a reference BLS provider course for
      lay persons is suggested as a tool for research. The course duration is 3 h 15
      min (excluding breaks), with 2 h 15 min practice time for the participants, 30
      min for theory and 20 min for practical demonstrations by the instructor. A
      manual is distributed at the start of the course. The ratio of instructors to
      participants is one to six. The lectures are interactive between the instructor
      and the participants. Cardiopulmonary resuscitation (CPR) is practised on
      manikins in groups of six. A formal BLS scenario test may be held at the end of
      the course as part of a research study or if the candidates so request. It is
      suggested that by using this reference course during research into lay person BLS
      teaching, it will be easier to make comparisons between different studies.

PMID- 16597482
TI  - Application of normothermic cardiac arrest algorithms to hypothermic cardiac
      arrest in a canine model.
AB  - BACKGROUND: International guidelines (2000) do not recommend vasopressor and
      antiarrhythmic medications during ventricular fibrillation (VF) with a core
      temperature below 30 degrees C. The efficacy of normothermic AHA algorithms using
      standard doses of epinephrine (EPI) (adrenaline) followed by amiodarone (AMIO) in
      hypothermic VF is uncertain. OBJECTIVES: To determine the effects of EPI followed
      by the combination of EPI/AMIO in the treatment of VF in a canine model of severe
      hypothermia. METHODS: An un-blinded, placebo controlled experiment using 21
      mechanically ventilated dogs. Coronary perfusion pressure (CPP), temperature, and
      electrocardiogram (ECG) were monitored. Animals were cooled to 22 degrees C or
      the onset of spontaneous VF. VF was induced if necessary. Animals in the
      treatment group received EPI (0.01 mg/kg IV) and defibrillation. This was
      followed by EPI (0.01 mg/kg IV), AMIO (10 mg/kg IV) and defibrillation if there
      was no sustained return of spontaneous circulation (ROSC) for 15 min. RESULTS:
      Mean CPP in the treatment group increased after the administration of EPI/AMIO
      (24.7+/-13.3 mmHg to 46.6+/-7.7 mmHg, p<0.004). Cumulatively, the administration
      of EPI followed by EPI/AMIO achieved ROSC after defibrillation in 10 of 11
      animals compared to 3 of 10 in the control group (91% versus 30%, n=21,
      p=0.0075). CONCLUSIONS: In this model of severe hypothermia, the use of standard
      2000 protocols for VF resulted in a significant increase of CPP, and, a higher
      ROSC rate compared to placebo controls. This study suggests that AHA normothermic
      algorithms may be beneficial in severe hypothermia.

PMID- 16597480
TI  - Inhibition of cholinesterase activity by azinphos-methyl in two freshwater
      invertebrates: Biomphalaria glabrata and Lumbriculus variegatus.
AB  - In this study, some biochemical features and the extent of inhibition induced by
      the organophosphorous pesticide azinphos-methyl on the cholinesterase (ChE)
      activity present in whole soft tissue of two freshwater invertebrate species, the
      gastropod Biomphalaria glabrata and the oligochaete Lumbriculus variegatus were
      investigated. Both invertebrate organisms presented marked differences in ChE
      activity, type of enzymes and subcellular location. Acetylthiocholine was the
      substrate preferred by B. glabrata ChE. The enzyme activity was located
      preferentially in the supernatant of 11,000 x g centrifugation and was inhibited
      by increasing concentrations of substrate but not by iso-OMPA. Results showed
      that there were progressive inhibitions of the enzyme activity, with values 21%,
      59%, 72%, 76%, and 82% lower than the control at levels of 1, 10, 50, 100 and
      1000 microM of eserine, respectively. In contrast, L. variegatus ChE activity was
      distributed both in the supernatant and pellet fractions, with values
      approximately 6 and 20 times higher than B. glabrata, respectively. Studies with
      butyrylthiocholine and iso-OMPA suggested that about 72% of the activity
      corresponded to butyrylcholinesterase. A strong enzyme inhibition (88-94%) was
      found at low eserine concentrations (1-10 microM). ChE activity from L.
      variegatus and B. glabrata was inhibited by in vivo exposure to azinphos-methyl
      suggesting that both species can form the oxon derivative of this pesticide.
      However, both invertebrate species showed a very different susceptibility to the
      insecticide. The NOEC and EIC50 values were 500 and 1000 times lower for L.
      variegatus than for B. glabrata, reflecting that the oligochaetes were much more
      sensitive organisms. A different pattern was also observed for the recovery of
      the enzymatic activity when the organisms were transferred to clean water. The
      recuperation process was faster for the oligochaetes than for the gastropods.
      Mortality was not observed in either of the experimental conditions assayed, not
      even at concentrations that induced 90% of ChE inhibition. The differences in
      substrate specificity, sensitivity to inhibitors, and subcellular location
      between the ChEs of B. glabrata and L. variegatus could be the main factors
      contributing to the differential susceptibility to azinphos-methyl ChE inhibition
      found in the present study.

PMID- 16597483
TI  - Assessment of somatosensory evoked potentials during resuscitation of a 15-year
      old boy with Duchenne muscular dystrophy.
AB  - Patients with Duchenne muscular dystrophy (DMD) are likely to suffer from cardiac
      insufficiency. Subclinical cardiac insufficiency may decompensate
      intraoperatively. During spinal surgery, recording of somatosensory evoked
      potentials (SSEP) is the standard method of spinal cord monitoring. Assessment of
      SSEP has proven to be a highly prognostic measure of neurological outcome after
      cardiopulmonary resuscitation (CPR). In the case presented, scalp SSEP as
      response to stimulation of both median and tibial nerves were recorded during
      spinal surgery in a 15-year-old boy with DMD. The patient developed severe
      hypotension and circulatory collapse intraoperatively. SSEP were measured before,
      during and up to 3h after circulatory collapse. He was successfully resuscitated
      and fully recovered. Latencies of SSEP remained stable from all extremities
      whereas amplitudes significantly decreased during CPR, but recovered completely
      within 3h. The amplitudes of SSEP serve as a more sensitive marker for brain
      ischaemia than latencies. Stability of latencies and full recovery of amplitudes
      within 3h indicated sufficient CPR and predicted a good neurological recovery.

PMID- 16597484
TI  - Application of Eichhornia crassipes and Pistia stratiotes for treatment of urban
      sewage in Israel.
AB  - The effectiveness of sewage purification by aquatic plants, such as water
      hyacinth (Eichhornia crassipes) and water lettuce (Pistia stratiotes), was tested
      on laboratory and pilot scales. Cascade and semi-continuous pilot experiments
      verified that the plants are capable of decreasing all tested indicators of water
      quality to levels that permit the use of the purified water for irrigation of
      tree crops. This applies to biochemical oxygen demand (BOD), chemical oxygen
      demand (COD), total suspended solids (TSS), and turbidity. The laboratory-scale
      tests confirm the capacity of the plants to reach and hold reasonably low levels
      of BOD (5-7 mg L(-1)) and COD (40-50 mg L(-1)) and very low levels of TSS (3-5 mg
      L(-1)) and turbidity (1-2 NTU). In the experimental pilot setup, with
      circulation, COD decreased from 460 to 100 mg L(-1) after 2.5-4 days of
      treatment, while 6-7 days were required to this end without circulation. This
      doubled the active pond area and provided a two-level hydraulic loading (8 and 12
      L min(-1)) with circulation that proved to be effective during the summer as well
      as the winter season. The outflow concentrations were 50-85 mg L(-1) of COD and 4
      6 mg L(-1) of BOD. The results show that the use of this free water surface flow
      system (FWS) and its low maintenance system for treatment of urban and
      agricultural sewage is a viable option.

PMID- 16597485
TI  - Robotic radical prostatectomy with the "Veil of Aphrodite" technique: histologic
      evidence of enhanced nerve sparing.
AB  - OBJECTIVE: We have recently described a modification (Veil of Aphrodite) designed
      to preserve the lateral prostatic fascia (LPF) during robotic prostatectomy.
      Here, we histologically compare the Veil of Aphrodite technique (VT) and standard
      nerve-sparing technique (ST). METHODS: Thirty-six consecutive prostatectomies
      performed by a single surgeon were processed by the whole-mount method. The right
      and left anterolateral (AL) zones of each prostate were independently evaluated
      for LPF, plane of excision, capsular incision/margin status, margin clearance,
      and quantitative analysis of periprostatic nerve bundles using S100 immunostain.
      RESULTS: There were 42 AL zones with ST and 30 with VT. In all 42 ST zones, the
      plane of excision was outside the prostate and a rim of LPF was present. The mean
      margin clearance was 1.4 mm (0.6-2.8 mm) and the mean nerve bundle count was 10
      (3-19). Capsular incision and margin status were negative in all 42. For VT, 24
      of 30 zones lacked LPF and the plane of excision ran just by the prostatic edge.
      The mean margin clearance was 0.3 mm (0-1.7 mm) and the mean nerve bundle count
      was two (0-11). Two VT AL zones revealed capsular incision; the margin was
      negative for tumour in all 30. Differences in the margin clearances and nerve
      bundle counts between ST and VT were statistically significant (p < 0.0001).
      CONCLUSIONS: The LPF contains nerve bundles that run along the surface of the AL
      zones. The VT is a safe procedure that effectively preserves the LPF and appears
      to provide enhanced nerve sparing as compared to the ST.

PMID- 16597486
TI  - ERK3 associates with MAP2 and is involved in glucose-induced insulin secretion.
AB  - The adaptation of pancreatic islets to pregnancy includes increased beta cell
      proliferation, expansion of islet mass, and increased insulin synthesis and
      secretion. Most of these adaptations are induced by prolactin (PRL). We have
      previously described that in vitro PRL treatment increases ERK3 expression in
      isolated rat pancreatic islets. This study shows that ERK3 is also upregulated
      during pregnancy. Islets from pregnant rats treated with antisense
      oligonucleotide targeted to the PRL receptor displayed a significant reduction in
      ERK3 expression. Immunohistochemical double-staining showed that ERK3 expression
      is restricted to pancreatic beta cells. Transfection with antisense
      oligonucleotide targeted to ERK3 abolished the insulin secretion stimulated by
      glucose in rat islets and by PMA in RINm5F cells. Therefore, we examined the
      participation of ERK3 in the activation of a cellular target involved in
      secretory events, the microtubule associated protein MAP2. PMA induced ERK3
      phosphorylation that was companied by an increase in ERK3/MAP2 association and
      MAP2 phosphorylation. These observations provide evidence that ERK3 is involved
      in the regulation of stimulus-secretion coupling in pancreatic beta cells.

PMID- 16597487
TI  - Removal of phosphate species from solution by adsorption onto calcite used as
      natural adsorbent.
AB  - Phosphates are very important basic materials in agricultural and other
      industrial applications. Phosphorus is often present in low concentrations in
      wastewater, almost solely in the form of organic and inorganic phosphates (ortho-
      and poly-phosphates). The removal of phosphates from surface waters is generally
      necessary to avoid problems, such as eutrophication, particularly near urban
      areas. The usual methods of treatment are either biological or physicochemical by
      sedimentation. This paper studies the removal of phosphate species by adsorption
      onto calcite used as natural adsorbent. The phosphate solutions were prepared
      artificially by adding certain quantities of K2HPO4 in water. The effect of
      equilibrium pH, phosphate/mineral ratio and contact time was studied. The results
      showed that pH plays an important role in the removal of phosphate species from
      solution, with removal being more efficient in the basic pH region. The
      experimental results also show that adsorption is also efficient for high ratios
      phosphate/adsorbent. Finally, the adsorption process is time dependent. Based on
      the experimental results a possible mechanism of phosphate removal onto calcite
      surface is proposed. As a general conclusion, phosphate species seem to be
      efficiently removed from solutions using calcite as natural adsorbent. In
      addition, the adsorption product can be used as fertilizer for acid soils.

PMID- 16597488
TI  - In vitro maturation of pig oocytes with different media, hormone and meiosis
      inhibitors.
AB  - This study evaluated in vitro maturation of pig oocytes in two maturation media
      (TCM199 and NCSU23) supplemented with 10% porcine follicular fluid (pFF) or 0.1%
      polyvinyl alcohol (PVA) and four hormonal treatments. The best media was then
      used to evaluate the effect of reversible meiosis inhibitors cycloheximide (5
      microgram/ml) [DOSAGE ERROR CORRECTED]and butyrolactone I (12.5M) on the
      maturation of pig oocytes was evaluated. After maturation for 44 h, the oocytes
      were fixed, stained, and examined under epifluorescence microscopy. The
      comparison of the proportion of oocytes in metaphase II revealed that hormonal
      treatment 2(incubation for 22 h - 10 ng EGF/ml, 10 IU hCG/ml and 10 IU eCG/ml,
      followed by incubation for 22 h - 10 ng EGF/ml) presented higher repeatability
      percentages: TCM+ PVA (54.5% - 61/112); TCM+ pFF (65.0% - 63/97);NCSU23 + PVA
      (54.6% - 65/119), and NCSU23 + pFF (58.1% - 61/105). The comparison of maturation
      media showed that TCM199 presented more constant results than NCSU23. Regarding
      supplementation with pFF or PVA, TCM199 with pFF presented better results. The
      comparison between butyrolactone I and cycloheximide demonstrated that both drugs
      effectively inhibited meiosis; however, only cycloheximide presented metaphase II
      percentages similar to the control (70.29% and 75.49%, respectively). In
      conclusion, it is recommended the use of TCM199 medium supplemented with pFF and
      hormonal treatment with 10 ng EGF/ml, 10 UI hCG/mland 10 UI eCG/ml during the
      first 22 h and more 22 h with 10 ng EGF/ml for the pig oocytes maturation.
      Butyrolactone I and cycloheximide effectively arrested/resumpted maturation;
      however, the oocytes percentages in metaphase II was the same for both
      cycloheximide and the control groups.

PMID- 16597489
TI  - The effect of crystal imperfections on particle fracture behaviour.
AB  - Micronisation of active pharmaceutical ingredients is a process which is
      sometimes difficult to control. The main purpose of this study was to assess the
      effect of the pre-existing flaws in the material to be milled. The rate of
      breakage of four samples of a model compound (sodium chloride), originating from
      different sources, was determined in a jet mill. It appeared that each type of
      sodium chloride has a distinct particle rate of breakage and breakage pattern.
      The numbers of flaws in the different types of sodium chloride have been
      determined by immersing the sodium chloride particles in a liquid with the same
      refractive index. This makes the cracks better visible. Microphotographs were
      made and flaws were counted manually. The study shows that the flaw density has
      an impact on the fracture behaviour of particles. The degree of fracture tends to
      increase with increasing flaw density. The paper shows however that the
      mechanical properties of the material as well as the starting particle size
      dominate the significance of the impact of flaws on fracture behaviour.

PMID- 16597490
TI  - Effects of pretreatment of needle puncture and sandpaper abrasion on the in vitro
      skin permeation of fluorescein isothiocyanate (FITC)-dextran.
AB  - Microneedle systems have gained attention as having many advantages over
      transdermal patches and hypodermic needles. The procedure provides adequate skin
      permeation rates without pain or severe infection. To obtain information for
      designing a microneedle system, macroneedles were used instead of microneedles to
      investigate the effects of pretreatment of needle puncture in the skin barrier
      stratum corneum on in vitro skin permeation of fluorescein isothiocyanate (FITC)
      dextrans (4.3, 9.6 and 42.0 kDa) (FD-4, FD-10 and FD-40). The effect of sandpaper
      abrasion was also investigated for comparison. Both pretreatments on the skin
      barrier significantly increased the skin permeation of FDs. Lactate dehydrogenase
      (LDH) leaching was measured after pretreatment of macroneedle and sandpaper
      abrasion on the skin to evaluate the skin damage by these pretreatment methods.
      Lower leaching of LDH was observed after macroneedle puncture than after
      sandpaper abrasion. Next, a parallel permeation-resistance model of the skin
      barrier was established. Skin permeation of FD-10 was predicted by the model as a
      function of the number of pores in the skin barrier. Our results suggest that
      needle puncture may provide a safe, efficient and controllable alternative for
      increasing transdermal drug delivery.

PMID- 16597491
TI  - Age-related structural and functional changes in the cochlear nucleus.
AB  - Presbycusis - age-related hearing loss - is a key communication disorder and
      chronic medical condition of our aged population. The cochlear nucleus is the
      major site of projections from the auditory portion of the inner ear. Relative to
      other levels of the peripheral and central auditory systems, relatively few
      studies have been conducted examining age-related changes in the cochlear
      nucleus. The neurophysiological investigations suggest declines in glycine
      mediated inhibition, reflected in increased firing rates in cochlear nucleus
      neurons from old animals relative to young adults. Biochemical investigations of
      glycine inhibition in the cochlear nucleus are consistent with the functional
      aging declines of this inhibitory neurotransmitter system that affect complex
      sound processing. Anatomical reductions in neurons of the cochlear nucleus and
      their output pathways can occur due to aging changes in the brain, as well as due
      to age-dependent plasticity of the cochlear nucleus in response to the age
      related loss of inputs from the cochlea, particularly from the basal, high
      frequency regions. Novel preventative and curative biomedical interventions in
      the future aimed at alleviating the hearing loss that comes with age, will likely
      emanate from increasing our knowledge and understanding of its neural and
      molecular bases. To the extent that this sensory deficit resides in the central
      auditory system, including the cochlear nucleus, future neural therapies will be
      able to improve hearing in the elderly.

PMID- 16597492
TI  - Multimodal approach to endovascular treatment of visceral artery aneurysms and
      pseudoaneurysms.
AB  - PURPOSE: To assess the feasibility and the effectiveness of endovascular
      treatment of visceral arteries aneurysms (VAAs) using a "multimodal approach".
      MATERIAL AND METHODS: Twenty-five patients (mean age 60.1 years) with 29 VAAs (13
      splenic, 4 hepatic, 3 gastroduodenal, 6 renal, 2 pancreatic-duodenal, 1 superior
      mesenteric) were considered suitable for endovascular treatment; 8/29 were
      ruptured. Saccular aneurysms (9/29) were treated by sac embolization with coils
      (in 4 cases associated with cyanoacrylate or thrombin) with preservation of
      artery patency. Fusiform aneurysms (6/29), were treated by an "endovascular
      exclusion". In 10/29 cases, supplied by a terminal branch, we performed an
      embolization of the afferent artery, with coils and cyanoacrylate or thrombin.
      2/29 cases were treated with a stent-graft and 2/29 cases with a percutaneous
      ultrasound-guided thrombin injection and coils embolization of the afferent
      artery. The follow-up was performed by ultrasonography and/or CT-angiography 1
      week after the procedure and then after 1, 6, and 12 months and thereafter
      annually. RESULTS: In 29/29 cases we obtained an immediate exclusion. Two patient
      died for other reasons. Complication rate was 27.6% (7 spleen ischemia and 1
      stent-graft occlusion). During the follow-up (range: 7 days-36 months, mean 18.7
      months), we observed 3/29 (10.3%) cases of reperfusion in the first month, all
      treated successfully with a further endovascular procedure. Primary technical
      success was 89.7%; secondary technical success was 100%. CONCLUSION: Endovascular
      therapy can be considered a feasible and effective approach for VAAs with good
      primary and secondary success rates.

PMID- 16597493
TI  - Differential pulse, square wave and adsorptive stripping voltammetric
      quantification of tianeptine in tablets.
AB  - Differential pulse polarographic (DPP) and square wave polarographic (SWP)
      techniques were applied at hanging mercury drop electrode (HMDE) for quantitative
      determination of tianeptine (TIA) in tablets. The adsorptive stripping
      voltammetric (ASV) behavior of TIA was also studied. TIA gave a sensitive
      reduction peaks at -1256, -1244 and -1072 mV for DPP, SWP and ASV, respectively
      (versus Ag/AgCl) in Britton-Robinson buffer (B-R buffer) at pH 11. The solution
      conditions and instrumental parameters were optimized for the determination of
      TIA in tablets. Calibration plots and regression data validation, accuracy,
      precision, limit of detection, limit of quantitation and other aspects of
      analytical merit are presented.

PMID- 16597494
TI  - Simultaneous determination of zonisamide, carbamazepine and carbamazepine-10,11
      epoxide in infant serum by high-performance liquid chromatography.
AB  - This study developed a simple method for the simultaneous determination of
      zonisamide (ZNS), carbamazepine (CBZ) and its active metabolite, carbamazepine
      10,11-epoxide (CBZE) in infant serum using reversed-phase high-performance liquid
      chromatograph (HPLC). The method involves a single-step protein precipitation
      procedure that uses no solid-phase or liquid-liquid extraction. The HPLC
      separation was carried out on a Cadenza CD-C18 column (3 microm, 4.6 mm x 150 mm)
      with potassium phosphate buffer (pH 4.6; 25 mM)-methanol-acetonitrile (65:20:15
      (v/v/v)) as a mobile phase at a 1.0 ml/min flow rate: ZNS was detectable using a
      UV detector at 235 nm, and both CBZ and CBZE were at 215 nm. The quantification
      limits were established in accordance with each therapeutic range at 2.5
      microg/ml for ZNS, 0.5 microg/ml for CBZ, and 0.25 microg/ml for CBZE. The
      respective coefficients of variation were 1.3-6.0% and 2.2-7.7% for the intra-
      and inter-assay.

PMID- 16597496
TI  - A set of duplicons on human chromosome 9 is involved in the origin of a
      supernumerary marker chromosome.
AB  - Human chromosome 9 is involved in a number of recurrent structural
      rearrangements; moreover, its pericentromeric region exhibits a remarkable
      evolutionary plasticity. In this study we present the molecular characterization
      of a constitutional rearrangement, involving the 9p21.1q13 region, which led to
      the formation of a supernumerary marker chromosome (SMC). We defined the sequence
      of the breakpoints and identified a new set of duplicons on human chromosome 9,
      named LCR9s (chromosome 9 low-copy repeats). Two of these duplicons were shown to
      be involved in a somatic exchange leading to the formation of the SMC. High
      resolution FISH coupled to database search demonstrated that a total number of 35
      LCR9 paralogs are present in the human genome. These newly described chromosome 9
      duplicons have features that may be crucial in driving structural chromosome
      rearrangements in germinal and somatic cells.

PMID- 16597495
TI  - Physician-patient communication: a study on the observed behaviours of specialty
      physicians and the ways their patients perceive them.
AB  - OBJECTIVE: To explore the communicative behaviours as used by specialty
      physicians, and their patients' perception of the communicative act as well as
      their satisfaction with the encounter. METHODS: Cross-sectional study involving
      27 specialty physicians and 257 outpatients. Encounters were video-recorded and
      analysed through the GATHA-ESP scale. Patients rated the quality of the
      interaction and their satisfaction with it in a questionnaire. RESULTS: Most
      specialist doctors use a "managerial" style where there is no exploration of
      their patients' emotions (22%), expectations (28%) or psychosocial aspects (10
      20%). Less than one doctor out of every four ever gave the patient an opportunity
      to participate in any type of decision making at the surgery. Patients were more
      satisfied with those encounters they felt more patient-centred (F: 11.37;
      p<0.001); higher scores on the GATHA-ESP characterised these visits. CONCLUSIONS:
      Specialty physicians show a limited range of communicative skills as they use a
      doctor-centred style that allows for little patient participation. Patients'
      perceptions of patient-centeredness are linked to satisfaction more than the
      analysis of doctors' behaviour at the consultation does. PRACTICE IMPLICATIONS:
      It seems important to foster training in communication skills in the different
      specialist vocational training programs. Studies on physician-patient
      communication should deal with the perceived and observed perspectives on this
      domain.

PMID- 16597498
TI  - Proteasomal proteolysis in anoxia-reoxygenation, preconditioning and
      postconditioning of isolated cardiomyocytes.
AB  - The role of proteasomal proteolysis in the pathogenesis of ischemia-reperfusion
      is being actively studied. To evaluate the participation of the proteasome in the
      preconditioning and postconditioning phenomena we used primary culture of
      neonatal cardiomyocytes. This culture was undergone 30min of anoxia followed by
      60min of reoxygenation. Preconditioning was modeled by three cycles of 3min
      anoxia followed by 3min reoxygenation. Postconditioning was modeled by three
      cycles of 1min reoxygenation followed by 1min anoxia, respectively. Clasto
      lactacystin beta-lactone, a specific proteasome inhibitor, was added to the
      culture medium right before the cycles of preconditioning or postconditioning in
      the dose that does not cause cell death (2.5muM). Percentages of living,
      necrotic, and apoptotic cells were determined by staining with bisbenzimide and
      propidium iodide. Autophagy was demonstrated by staining vacuolar structures with
      monodansyl cadaverine. Proteasomal activity was determined by cleavage intensity
      of specific fluorogenic substrates. Trypsin-like, chymotrypsin-like and peptidyl
      glutamyl peptide-hydrolyzing (PGPH) activities were decreased after anoxia.
      Reoxygenation has led to the increase in trypsin-like and chymotrypsin-like
      activities comparing to anoxia, but these parameters have never reached the
      control levels. PGPH activity has been restored up to the initial level.
      Preconditioning and postconditioning increased numbers of living cells and
      decreased that of necrotic, apoptotic and autophagic cells. Paradoxically, it was
      established that proteasome inhibitors prevented the necrotic and apoptotic cell
      death of cardiomyocytes in anoxia-reoxygenation, but in the same concentration
      abolished the effects of preconditioning and postconditioning. Low doses of
      proteasome inhibitors, particularly the ones used in our experiments, resulted in
      the abolishing of preconditioning and postconditioning phenomena, but at the same
      time led to the increase of the population of living cells in anoxia
      reoxygenation, and can be considered as potential pharmacological agents of
      preconditioning and postconditioning.

PMID- 16597497
TI  - Activation of genes for growth factor and cytokine pathways late in chondrogenic
      differentiation of ATDC5 cells.
AB  - The mouse embryonal carcinoma cell line ATDC5 provides an excellent model system
      for chondrogenesis in vitro. To understand better the molecular mechanisms of
      endochondral bone formation, we investigated gene expression profiles during the
      differentiation course of ATDC5 cells, using an in-house microarray harboring
      full-length-enriched cDNAs. For 28 days following chondrogenic induction, 507
      genes were up- or down-regulated at least 1.5-fold. These genes were classified
      into five clusters based on their expression patterns. Genes for growth factor
      and cytokine pathways were significantly enriched in the cluster characterized by
      increases in expression during late stages of chondrocyte differentiation. mRNAs
      for decorin and osteoglycin, which have been shown to bind to transforming growth
      factors-beta and bone morphogenetic proteins, respectively, were found in this
      cluster and were detected in hypertrophic chondrocytes of developing mouse bones
      by in situ hybridization analysis. Taken together with assigned functions of
      individual genes in the cluster, interdigitated interaction between a number of
      intercellular signaling molecules is likely to take place in the late
      chondrogenic stage for autocrine and paracrine regulation among chondrocytes, as
      well as for chemoattraction and stimulation of progenitor cells of other
      lineages.

PMID- 16597499
TI  - [Benefit of the extended-release methylphenidate formulations: a comparative
      study in childhood].
AB  - Methylphenidate (MPH) is a potential therapeutic tool for Attention Deficit with
      Hyperactivity Disorders (ADHD). In addition to the immediate-release formulation,
      Ritalin, two extended-release formulations, Ritalin LA and Concerta are available
      and allow a once-daily administration. We compared the respective benefits of
      both formulations for the patients and their family in terms of efficacy,
      handling and tolerance. PATIENTS AND METHODS: This prospective study was based on
      30 children aged 6 to 15 years. All patients had a confirmed ADHD and were
      efficiently treated with Ritalin. The children were consecutively treated with
      Ritalin LA and Concerta, with a comparable MPH daily dosage, during 2 months for
      each molecule. The 3 drugs were evaluated individually and comparatively through
      a battery of questionnaires submitted to the parents and the teachers of each
      child. RESULTS: Extended-release MPH efficacy was comparable to the immediate
      release formulation, Ritalin. For both of them, the once-daily administration
      appeared beneficial. Concerta was finally prescribed in 18 children, Ritalin LA
      in 8 cases and Ritalin in 4 cases. In each case the medical choice was consistent
      with the parents preference. Concerta was appreciated for its persisting efficacy
      in late afternoon during homework. Concerta and Ritalin LA did not induce
      significant adverse effects, especially regarding alimentation and sleep.
      CONCLUSIONS: MPH therapy in ADHD carries an excellent risk/benefit ratio without
      addictive induced behaviours. The extended-release MPH formulations provide an
      improvement for the patients in keeping with Ritalin efficacy through a once
      daily administration. Regardless of its formulation, MPH indications and
      guidelines must be respected.

PMID- 16597500
TI  - Private specificities of heterologous immunity.
AB  - Antiviral T-cell responses between individuals that have similar major
      histocompatibility complex molecules share similarities in epitope hierarchies
      and T-cell receptor variable gene usage (public specificities), yet the T-cell
      receptor amino acid sequences differ between individuals (private specificities).
      The significance of the private specificities of these repertoires is brought
      about under conditions of heterologous immunity and might have important
      consequences in anti-viral immunity and immunopathology.

PMID- 16597502
TI  - Laryngeal dystonia causing upper airway obstruction in progressive supranuclear
      palsy.
AB  - A 58-year-old man with progressive supranuclear palsy (PSP) developed two
      episodes of respiratory failure associated with laryngeal spasm. It was revealed
      he had adductor laryngeal breathing dystonia, a relatively unrecognized
      complication of PSP.

PMID- 16597501
TI  - Bronchial asthma as neurogenic paroxysmal inflammatory disease: a randomized
      trial with carbamazepine.
AB  - PURPOSE: Based on the assumption that bronchial asthma has not only inflammatory,
      but also certain neurogenic paroxysmal mechanism and pathophysiological links
      with other non-epileptic paroxysmal inflammatory diseases--migraine and
      trigeminal neuralgia, we decided to investigate efficacy of antiepileptic drug
      carbamazepine in patients with moderate persistent or severe asthma. METHODS:
      Sixty-three patients completed randomized double-blind, placebo-controlled trial.
      RESULTS: Stable remission was achieved after carbamazepine treatment in 25
      patients in active group (n=33). No significant improvement was registered in
      patients of placebo group (n=30). Following open-label treatment shows high and
      stable antiasthmatic efficacy of carbamazepine monotherapy. CONCLUSIONS:
      Carbamazepine showed high efficacy in therapy of moderate persistent or severe
      bronchial asthma. Antiasthmatic activity of carbamazepine can be considered as
      influence on neurogenic mechanisms of asthma. We suppose that it is possible to
      use carbamazepine for therapy of bronchial asthma in clinical practice.

PMID- 16597503
TI  - Mycophenolate mofetil - as an adjunctive immunosuppressive therapy in refractory
      myasthenia gravis: The Singapore experience.
AB  - We report our experience, using mycophenolate mofetil (MyM) as an adjunctive
      immunosuppressive therapy in patients with severe, refractory and high dose
      steroid-dependent myasthenia gravis (MG). Five patients were commenced on MyM in
      addition to other immunosuppressive therapies. All had significant clinical
      improvement and no subsequent myasthenic crisis requiring intensive care unit
      admission. MyM was well tolerated and no serious adverse effects were observed.
      MyM is an effective adjunctive therapy for the treatment of severe, refractory
      and steroid-dependent MG in our experience.

PMID- 16597504
TI  - Stereological study of the effects of nandrolone decanoate on the rat prostate.
AB  - It has been shown that nandrolone decanoate which is one of the anabolic
      androgenic steroid compounds changes the testis structure and sperm quality but
      quantitative studies of the prostate have received less attention. Control rats
      received the peanut oil and experimental group received nandrolone decanoate for
      14 weeks. Then the rats were left untreated for 14 weeks. After 14 weeks of
      withdrawal, the prostate was studied using stereological methods. The mean
      prostate weight decreased approximately 39% (p<0.009) in nandrolone decanoate
      treated rats. The mean total prostate volume, glands, epithelia, fluids and
      collagen bundles reduced approximately 30% (p<0.03), approximately 31% (p<0.03),
      approximately 41% (p<0.02), approximately 31% (p<0.05) and approximately 59.5%
      (p<0.02) in the experimental group. The mean total luminal surface of the glands
      and total length of the vessels decreased approximately 40% (p<0.02) and
      approximately 46% (p<0.009), respectively, in the nandrolone decanoate treated
      rats. The height of epithelium did show no difference. It can be concluded that
      nandrolone decanoate causes atrophic changes in the components of rat prostate.

PMID- 16597506
TI  - Synthesis of tungsten nanoparticles by sonoelectrochemistry.
AB  - Tungsten nanoparticles have been synthesized by the sonoelectrochemical method.
      The electrolyte contained the tri-sodium citrate, sodium tungstate, ferrous
      sulphate, and citric acid. A platinum slice was used as the anode and a titanium
      alloy horn as the cathode. Twenty kilohertz ultrasound generated by an ultrasound
      generator was connected to the titanium-alloy horn as an amplitude converter. Due
      to the electrochemical reaction and the cavitation effect of the ultrasound, the
      iron-tungsten aggregates at the cathode were dispersed into the electrolyte and
      iron atoms were dissolved in the acidic environment. In this way, body-center
      cubic (bcc) tungsten nanoparticles have been obtained by controlling the density
      of the electric current, the ultrasound pulse period and amplitude. Their
      morphology, structure, and chemical components have been characterized using
      transmission electron microscope (TEM) and X-ray photoelectron spectrometer
      (XPS).

PMID- 16597505
TI  - Mechanisms underlying dysfunction of carotid arteries in genetically
      hyperlipidemic rabbits.
AB  - In the present study we compared the vascular reactivity and integrity of the
      nitric oxide (NO)-cyclic 3',5'-guanosine monophopsphate (cGMP) pathway in carotid
      arteries of hyper- and normolipidemic rabbits. Vasodilation to acetylcholine,
      nitroglycerin, and sodium nitroprusside was desensitized in hyperlipidemia, but
      the nitroprusside-induced relaxation was normalized by an NO synthase inhibitor
      in endothelium-intact and -denuded vessels. Hyperlipidemic carotid arteries
      exhibited increased basal NO (detected by EPR spin-trapping) and reactive oxygen
      species formation (detected by chemiluminescence), whereas acetylcholine-induced
      NO formation was nearly abolished. Hyperlipidemia increased NADPH-dependent
      superoxide formation in carotid membranes, and carotid cryosections stained with
      the fluorescent dye dihydroethidium revealed increased endothelial and medial
      reactive oxygen species formation. Hyperlipidemia elicited macrophage invasion
      into the carotid wall, as detected by a dot-immunoblot. The basal activity of
      cGMP-dependent proteinkinase, the nitroprusside-stimulated activity of soluble
      guanylyl cyclase, and its protein expression were decreased by hyperlipidemia.
      The cGMP phosphodiesterase activity was marginally increased by hyperlipidemia,
      such that the ratio of cGMP-forming vs. -degrading capacity was decreased by 2
      fold. Hyperlipidemia triggers infiltration of macrophages into the carotid wall
      and endothelial as well as smooth muscle superoxide formation. Consequently,
      relaxation of the carotid arteries are impaired due to smooth muscle and
      endothelial dysfunction.

PMID- 16597507
TI  - Resonance frequency analysis of implants in the guinea pig model: influence of
      boundary conditions and orientation of the transducer.
AB  - The goal of this study was to identify the parameters that must be controlled
      during in vivo resonance frequency measurements with a custom Osstell transducer
      for custom implants in the guinea pig animal model. A numerical study and in
      vitro measurements were performed to determine the influence of the boundary
      conditions as well as the transducer orientation on the resonance frequency
      measured by the custom Osstell transducer. In the reported guinea pig model, the
      type of boundary condition, the orientation of the transducer (parallel or
      perpendicular to the long axis of the bone) and the length of the modelled bone
      have a large influence on the resonance frequency values. This implies that a
      follow-up in time of the stability of an implant requires the boundary conditions
      applied to the bone in which the implant is installed as well as the orientation
      of the transducer to be highly repeatable. Applying controlled boundary
      conditions during in vivo measurements had a highly positive influence on the
      repeatability of the Osstell measurements. This improves the possibility of the
      technique to measure changes in the implant-bone interface during healing of the
      implant.

PMID- 16597508
TI  - Recycling or regulation? The role of amino-terminal modifying enzymes.
AB  - Post-translational modifications are essential for a variety of functions, such
      as the translocation, activation, regulation, and, ultimately, degradation of
      proteins. The amino-terminal (N-terminal) region is a particularly active area
      for such alterations. Three types of reactions predominate: limited proteolysis
      to remove one or more amino acids; modification of the alpha-amino group; and
      side-chain-specific changes. The N-terminal peptidases expose penultimate
      residues, providing new substrates for peptidase or transferase action. These
      enzymes can act sequentially or competitively to influence a protein's longevity,
      location or activity. N-terminal modifying enzymes (NTMEs) might target a protein
      for ubiquitination and degradation or protect a protein from rapid turnover. The
      N-terminal peptidases might also have important roles in processing the peptides
      that are released from the proteasome. Plant NTMEs have roles in senescence,
      meiosis and defense, and proposed roles in polar auxin transport.

PMID- 16597509
TI  - The value of an evidence database for occupational therapists: an international
      online survey.
AB  - BACKGROUND: Online evidence databases can provide access to high quality evidence
      at the point of care, making evidence-based practice more achievable. A
      discipline-specific online bibliographic database called OTseeker
      (www.otseeker.com) was designed for use by occupational therapists. The database
      is free, and contains citations and abstracts of systematic reviews, and
      critically appraised randomized controlled trials relevant to occupational
      therapy. OBJECTIVES: The aim of this study was to investigate search practices of
      database users, their views on its functionality, and the reported impact, if
      any, on their practice from using OTseeker. DESIGN: An online survey, placed on
      the database website for 30 days. SAMPLE: Potential participants were users of
      OTseeker during a 30-day period. A total of 498 people who had used the database
      more than once from over 40 countries completed the survey. RESULTS: Three
      hundred and nine (62%) participants believed that OTseeker had improved their
      ability to locate research about the effectiveness of occupational therapy
      interventions, and 92 (19%) agreed that the information in the database had
      contributed to a change in practice. Those reporting no practice changes agreed
      that use of OTseeker had improved their knowledge generally (n=189; 38%),
      confirmed their practice (n=75; 15%), or revealed that there was insufficient
      research relevant to their search topic (n=92; 19%). Features of the database
      which helped respondents locate research evidence included: having discipline
      specific content, providing critical appraisal ratings for randomized controlled
      trials, and presenting search results ranked for methodological quality.
      CONCLUSION: This study confirms the value of a discipline-specific, online
      database for helping occupational therapists locate high quality research
      evidence. Information located on databases such as OTseeker can help change or
      confirm practice, and improve knowledge.

PMID- 16597510
TI  - Yellow fever vaccine-associated viscerotropic disease and death in Spain.
AB  - Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a recently
      described severe adverse event after yellow fever vaccination, and some cases
      have been reported in different countries [Anonymous. Effects of yellow fever and
      vaccination. Lancet 2001;358(9296):1907-9]. Herein we describe a YEL-AVD case in
      a young woman, who died after vaccination with 17D-204 strain. Clinical,
      serological and immunochemical analysis as well as virus detection,
      quantification, sequence analysis and cytokine release, were performed. Further
      investigations on yellow fever vaccine adverse events, and carefully analysis of
      the immune response elicited are important tasks for the future.

PMID- 16597511
TI  - Potential risk of pathogen transmission by acaricide-poisoned ticks.
AB  - Many aspects of tick poisoning with acaricides have yet to be elucidated. One of
      them is the influence of acaricide poisoning on tick infectivity to their hosts.
      To clarify this problem, we should know how tick poisoning develops after
      acaricide application. Data obtained during more than three decades of work with
      ticks of various species and with acaricides of different groups are presented in
      the paper. The first important phenomenon found was the gradual and progressive
      development of toxic symptoms after acaricide application, with death of the
      treated ticks delayed for days or even weeks ('slow-death syndrome'). The
      development of symptoms was much faster after the application of fenthion, an
      organophosphorous acaricide, when compared to DDT, a chlorinated hydrocarbon. The
      larger the adult ticks of a particular species, the more refractory they were to
      acaricide action. The duration of the development of toxic symptoms directly
      correlates with the degree of species-specific refractoriness. A special index
      T(LD(50)) (T(LC(50)) was introduced for comparing the duration of the poisoning
      development between different tick species, populations etc. The index determines
      the time when the final mortality is reached after using the LD(50) of a
      particular acaricide. Another index , T(LD(90)), was used for practical purposes.
      The values of these indices decreased with increasing age of tick populations.
      The prolonged duration of poisoning was also observed in nymphal ticks of species
      with a prolonged life-span and the ability to over-winter (Ixodes, Haemaphysalis)
      but not in ticks characterized by a short life-span (Dermacentor). During the
      entire period of poisoning, from acaricide application until tick death, the
      individual tick passes through six stages defined by its locomotor capabilities.
      The stages are the same for nymphs and adults of both hard and soft ticks after
      treatment with various acaricides. When ticks are at the initial stages of
      poisoning (1st to 3rd stage for DDT or 1st to 2nd for fenthion), they can attach
      to hosts and imbibe blood. The average body weight of such ticks after repletion
      corresponded to that of control ticks. Engorged nymphal ticks normally molted to
      adults, engorged females normally oviposited, and their progeny did not differ
      from the progeny of control females. This second important phenomenon, called
      'overcoming the poisoning', was observed in all studied species of ticks from
      several genera. Thus, the slow development of tick poisoning creates a potential
      for ticks to attach to hosts and to gorge blood, and for infected ticks to
      transmit pathogens to those hosts, while the ability to overcome the poisoning
      allows the ticks to survive and makes possible the subsequent trans-stadial and
      transovarial passage of pathogens. These data can be considered as strong
      circumstantial evidence of the risk that ticks can present to humans and animals
      at the initial stages of poisoning after acaricide treatment.

PMID- 16597512
TI  - Prevalence of hot weather conditions related to sports participation guidelines:
      a South Australian investigation.
AB  - BACKGROUND: There is scant guidance in the literature on the most appropriate
      Australian measures of, and thresholds for, extreme heat regarding giving advice
      on safe sports participation in hot weather. The purpose of this paper is to
      present a process for investigating two common measures of heat (air temperature,
      wet bulb globe temperature (WGBT)) in one state in Australia (South Australia),
      regarding their usefulness in making decisions regarding sports participation in
      the heat. METHOD: Commonly reported measures and thresholds of extreme heat were
      identified from a systematic review of guidelines regarding sports participation
      in hot weather. Dry air temperature (threshold of 35 degrees C), and WBGT index
      (threshold of 28 degrees C) were highlighted. Repeated daily measures of dry air
      temperature by the Bureau of Meteorology (BoM) and WBGT index from 12
      meteorological recording sites in South Australia (SA) for four consecutive
      summer periods (2000-2004) were analysed using these thresholds to investigate
      the prevalence of extremely hot temperatures in SA during these periods. The
      extremely hot hours-per-day data were standardised using a denominator of per-day
      month across the 12 SA recording regions. RESULTS: Across the four summer seasons
      of data in SA, there were similar standardised numbers of hours-per-day of
      extremely hot dry air temperature and WBGT index. There was a high correlation
      between these hours of hot weather measures, highlighting the congruence between
      hot air and humidity measures. Three distinct regional site groupings were
      identified, in which there was a different prevalence of extremely hot weather
      conditions. CONCLUSION: In SA, dry air temperature is an appropriate and robust
      measure of extreme heat related to sports participation, this measure providing
      as much information as WBGT in identifying extremely hot periods of weather. Dry
      air temperature can be readily measured by sports participants or officials
      irrespective of the geographical location in SA. Three SA regions demonstrated
      distinct differences in prevalence of extremely hot conditions, suggesting the
      need for site-specific interpretation of heat participation guidelines to ensure
      sports safety in hot weather. Other states in Australia could use the approach
      outlined in this paper to identify the most appropriate measure of extreme heat
      relevant to local conditions, and to assist in interpreting heat limit guidelines
      in a local context.

PMID- 16597514
TI  - Differential expression of LIM domain-only (LMO) genes in the developing mouse
      inner ear.
AB  - The vertebrate inner ear, a complex sensory organ with vestibular and auditory
      functions, is derived from a single ectoderm structure called the otic placode.
      Currently, the molecular mechanisms governing the differentiation and
      specification of the otic epithelium are poorly understood. We present here a
      detailed expression study of LMO1-4 in the developing mouse inner ear using a
      combination of in situ hybridization and immunohistochemistry. LMO1 is
      specifically expressed in the vestibular and cochlear hair cells as well as the
      vestibular ganglia of the developing inner ear. LMO2 expression is detected in
      the periotic mesenchyme of the developing mouse cochlea from E12.5 to E14.5. The
      expression of LMO3 expression is first observed in the cochlea at E13.5 and
      becomes confined to the lesser epithelial ridge (LER) from E14.5 to E17.5. LMO3
      is also expressed in some of the vestibular ganglion cells. LMO4 is initially
      expressed in the dorsolateral portion of the otic vesicle and its expression
      persists in the semicircular canals, macula, crista, and the spiral ganglia
      throughout embryogenesis. Thus, the regionalized expression patterns of LMO1-4
      are closely associated with the morphogenesis of the inner ear.

PMID- 16597516
TI  - HPLC in reversed phase mode: Tool for investigation of kinetics of blackcurrant
      seed oil lipolysis in supercritical carbon dioxide.
AB  - Blackcurrant (Ribes nigrum) seed oil is rich in alpha- and gamma-linolenic acids,
      the latter in particular being of potential use in medicine. The enzymatic
      hydrolysis of the oil was carried out in supercritical carbon dioxide using
      lipase Lipozyme as catalyst and changes in the composition of acylglycerols were
      recorded. Mono-, di-, and triacylglycerols and free fatty acids were separated by
      non-aqueous high-performance liquid chromatography in reversed phase mode and
      detected by UV diode array and 1H NMR detectors. Lipozyme was found to exert low
      specificity to individual fatty acids in the hydrolysed oil.

PMID- 16597515
TI  - Dynamic expression of the LIM-homeodomain gene Lhx15 through larval brain
      development of the sea lamprey (Petromyzon marinus).
AB  - LIM-homeodomain genes encode a family of transcription factors with highly
      conserved roles in the patterning and regionalisation of the vertebrate brain.
      The expression of one of those genes, Lhx15, in the embryonic lamprey brain,
      characterises precise functional subdivisions. In order to analyse the non
      embryonic development of the lamprey brain, we chose this gene to perform in situ
      hybridisations in Petromyzon marinus larvae of different ages. We demonstrate the
      usefulness of Lhx15 to follow the development and morphogenesis of brain
      structures and show the dynamical expression of this gene through time.
      Furthermore, we provide evidence for the evolutionary conservation of the
      expression of this gene in the spinal cord, notochord and urogenital system.

PMID- 16597517
TI  - Simple approaches to close the open structure of microfluidic chips and
      connecting them to the macro-world.
AB  - Microchip electrophoresis has a great potential to improve the speed and
      throughput of chemical and biochemical analyses. Conventional electrophoresis
      microchip fabrication methods comprise the main steps of channel formation, cover
      plate binding and access hole construction. While the fabrication of appropriate
      cover plates and their bonding process are quite essential to the creation of
      closed microfluidic networks, connection means of microchips to the macro-world
      is one of the most important parts of microchip fabrication. In this paper the
      most commonly used approaches are discussed for cover plate connector fabrication
      in conjunction with high and low temperature glue-less binding processes. The
      microchannels in the glass substrate were fabricated by sawing and powder
      blasting under regular laboratory settings, i.e., not necessitating the use of a
      clean-room environment, making in this way broader availability for
      electrophoresis microchip technology.

PMID- 16597518
TI  - Doping control for metandienone using hair analyzed by gas chromatography-tandem
      mass spectrometry.
AB  - A sensitive, specific and reproducible method for the quantitative determination
      of the anabolic metandienone in human hair has been developed. The preparation
      involved a decontamination step with methylene chloride. The hair sample (about
      50 mg) was solubilised in 1 ml 1 M NaOH, 10 min at 95 degrees C, in presence of 2
      ng of nandrolone-d(3) used as internal standard. The homogenate was neutralized
      and extracted using consecutively a solid-phase extraction (Isolute C(18) eluted
      with methanol) and a liquid-liquid extraction with pentane. The residue was
      derivatized by adding 5 microl MSTFA/NH(4)I/2-mercaptoethanol (250 microl; 5 mg;
      15 microl) and 45 microl MSTFA, then incubated for 20 min at 60 degrees C. A 1
      microl aliquot of derivatized extract was injected into the column (HP5-MS
      capillary column, 5% phenyl-95% methylsiloxane, 30 m x 0.32 mm i.d., 0.25 microm
      film thickness) of a Hewlett Packard (Palo Alto, CA, USA) gas chromatograph (6890
      Series). Metandienone was identified using three transitions (its daughter ions
      at m/z 339 and 206 for the parent 444 and 191 for 206) using a Waters Quattro
      Micro MS-MS system. The transition m/z 444 to 206 has been used as quantification
      transition and the others as identification transitions. The assay was capable of
      detecting 2 pg/mg of metandienone when approximately 50 mg of hair material was
      processed. Linearity was observed for metandienone concentrations ranging from 2
      to 500 pg/mg with a correlation coefficient of 0.9997. Intra-day and between-day
      precisions at 50 pg/mg were 13.4-16.5% and 22.0%, respectively, with an
      extraction recovery of 48%. The analysis of hair, cut into four segments,
      obtained from an athlete, revealed the presence of metandienone at the
      concentrations of 78, 7, 10 and 108 pg/mg in each segment of hair (0-1, 1-2, 2-3
      and 3 cm to the tip).

PMID- 16597521
TI  - Peer review: evolution or revolution?

PMID- 16597519
TI  - Analysis of veterinary drug residues in shrimp: a multi-class method by liquid
      chromatography-quadrupole ion trap mass spectrometry.
AB  - A liquid chromatography-mass spectrometry (LC-MS) method was developed to screen
      and confirm veterinary drug residues in raw shrimp meat. This method
      simultaneously monitors 18 drugs of different classes, including oxytetracycline
      (OTC), sulfonamides, quinolones, cationic dyes, and toltrazuril sulfone (TOLS).
      The homogenized shrimp meat is extracted with 5% trichloroacetic acid. The
      extract is further cleaned using polymer-based SPE. A 50 mm phenyl column
      separates the analytes, prior to analysis with an ion trap mass spectrometer
      interfaced with an atmospheric pressure chemical ionization source. This method
      is able to confirm oxytetracycline residues at 200 ng/g, toltrazuril sulfone at
      50 ng/g, sulfaquinoxaline at 20 ng/g, and the other 15 drugs at 10 ng/g or lower
      levels. An estimate of the level of residues can also be made so that only
      confirmed samples above action levels will be sent for quantitation. The method
      is validated with both fortified and incurred samples, using multiple shrimp
      species as well. This multi-class method can provide a means to simultaneously
      monitor for a wide range of illegal drug residues in shrimp.

PMID- 16597522
TI  - President's message March 2006.

PMID- 16597523
TI  - Ratings and rankings: judging the evaluation of quality.

PMID- 16597524
TI  - Voting rights for older Americans with dementia: implications for health care
      providers.
AB  - As the population of the United States ages, the prevalence of dementias such as
      Alzheimer's disease (AD) will increase. With this demographic shift, some older
      registered voters will lack the cognitive ability to weigh the variables involved
      in voting and making an informed decision at the ballot. Ramifications of this
      situation have only recently been considered. Medical and legal procedures to
      delineate the capacity to vote are lacking in our national policy and are in need
      of an overhaul. Caution must be taken to avoid indiscriminant disenfranchisement
      of people with dementia. Health care providers play a pivotal role in supporting
      older adults with dementia who exercise their voting rights. The purpose of this
      article is to discuss issues related to voting and older adults with dementia.
      Implications for gerontological health care providers are presented.

PMID- 16597525
TI  - Nurse delegation of medication administration for older adults in assisted
      living.
AB  - Assisted living (AL) is a relatively new form of long-term care that offers
      residents personal care services and more independence in a home-like
      environment. Introduced to the United States in the 1980s, AL is changing the
      conventional thinking about how to care for frail older adults. One important
      issue to explore is registered nurse (RN) delegation to unlicensed assistive
      personnel (UAP), particularly for medication administration. This study provides
      a national perspective on medication delivery in AL settings from the
      perspectives of state Board of Nursing (BON) executives. Qualitative interviews
      using semi-structured interview guides were conducted with BON executives to
      validate a legal summary of AL regulations and nurse practice acts, and to
      identify nursing issues pertaining to medication management in AL across the
      United States. In this study, there was considerable variation across states
      regarding medication administration and the role of both the RN and the UAP. BON
      executives displayed a range of knowledge about nursing practice issues in AL,
      with many reporting low familiarity with this setting. Mechanisms for systematic
      review of quality of delegation were not in place. Medication administration and
      nurse delegation were dynamic issues, with practice and policy evolving
      concurrently. This study highlights the limited articulation of policies between
      agencies and across states in the important and growing setting of assisted
      living. Nurses have the opportunity to shape this evolving practice arena and to
      enhance awareness of the professional and clinical issues inherent in working
      with UAP in medication delivery.

PMID- 16597526
TI  - National consensus on data elements for nurse managed health centers.
AB  - This report presents a summary of the findings from the National Network for
      Nurse Managed Health Centers Data Consensus Conference. Nationally, nurse-managed
      health centers are increasingly offering communities another option for access to
      high-quality primary care. The lack of agreed upon, standardized data elements
      for these centers has limited the ability to present clear information about
      their contributions as well as to inform policy related to their support and
      development. Fifty-three national invitees came to consensus in Washington, DC on
      the critical data elements for a national database for nurse-managed health
      centers. This database includes both clinical and financial/business practices
      elements. Consensus was not reached around some clinical areas. These areas are
      briefly discussed as well as the plans for next stages of data collection.

PMID- 16597527
TI  - Reporting near-miss events in nursing homes.
AB  - Since the Institute of Medicine report To Err Is Human was published in 1999,
      improving patient safety has become a major initiative for nurses working in all
      care settings. Nursing homes are a fertile environment for both a high frequency
      of adverse events to occur and a high number of institutional barriers to
      reporting them. This article outlines the barriers to reporting adverse events in
      nursing homes and provides support for why reporting near-miss events can serve
      as a means of reducing these barriers. It also provides recommendations and
      specific strategies for how to implement near-miss reporting systems in nursing
      homes such as policy changes, supportive leadership, and educating nurses about
      near-miss events. Further nursing research in this evolving area of patient
      safety is warranted.

PMID- 16597528
TI  - The Quality Chasm reports, evidence-based practice, and nursing's response to
      improve healthcare.
AB  - In a growing set of landmark reports, the Institute of Medicine (IOM) set in
      motion a sweeping quality initiative for reform of the healthcare system. Many of
      the recommendations incorporate evidence-based practice applications. Key points
      from the primary IOM reports are brought together. In the keystone report, the
      IOM offers analysis of the current health system and provides a blue print for
      change. Subsequent reports in the same series advance the blueprint by providing
      exemplars of quality healthcare, identifying clinical priority targets for
      corrective action, and recommending changes in education of health professionals.
      This article explores the role of healthcare professionals, specifically nurses,
      in improving healthcare in context of these reports and discusses how evidence
      based practice closes the chasm. Health professionals will be expected to make
      changes in practice and education. Crucial on the healthcare team, nurses are
      major players in the healthcare reformation that has been set into motion.

PMID- 16597529
TI  - Determining criteria for excellence in nurse practitioner education: use of the
      Delphi Technique.
AB  - Standards and guidelines are available to help nurse practitioner (NP) educators
      maintain quality in their programs. NP education is now at a juncture to develop
      criteria that extend beyond the basic standards to measurement of exemplary
      educational endeavors. In 2000, the National Organization of Nurse Practitioner
      Faculties Task Force for Programs of Excellence was formed and given the charge
      of developing criteria for recognizing exemplary nurse practitioner programs.
      This article reports on results and recommendations that evolved from a Delphi
      study to identify a set of criteria for excellence in NP programs. Thirteen
      expert panelists from across the United States participated in three rounds of
      iterations to evaluate the relevance, specificity, and comprehensiveness of 14
      initial criteria and reached consensus on nine final criteria. Finally, the paper
      discusses ways that these criteria may be used to improve NP education through
      the development of a program to recognize excellence in NP education.

PMID- 16597532
TI  - The surgical team and outcomes management: focus on postoperative ileus.
AB  - Postoperative ileus (POI) is defined as the impairment of bowel motility that
      occurs almost universally after major open abdominal procedures, as well as other
      abdominal and nonabdominal procedures. For the majority of affected patients, POI
      generally lasts approximately three to five days, but longer duration is not
      uncommon. The causes of POI are multifactorial, but can be broadly categorized
      into two groups: those related to the surgical procedure and those related to
      pharmacologic interventions (opioids). The fact that POI is generally transient
      and therefore self-limited should not deter the surgical team from seeking
      improved ways to mitigate its associated adverse effects, which can be
      substantial and immensely uncomfortable for the patient, and can have far
      reaching implications regarding overall hospitalization costs for many types of
      surgeries. Optimization of POI management and prevention efforts is a
      responsibility of all members of the surgical team and can drastically affect the
      overall clinical outcome of major abdominal surgery. Depending on the individual
      team member's role, different perspectives and strategies may be used to achieve
      improved outcomes, including but not limited to hospitalization costs related to
      care and length of stay, resource utilization, and, perhaps most critically,
      patient quality of life not only immediately after surgery but also after
      discharge. The ability to reliably and significantly decrease the duration of POI
      should be readily recognized as an important objective in the management of this
      condition. Opioids will continue to be a mainstay of postoperative care regimens,
      but new agents such as peripherally acting mu-opioid-receptor antagonists may
      offer a unique clinical advantage by helping to reduce the adverse
      gastrointestinal effects of opioids while preserving their desired benefits for
      postoperative analgesia.

PMID- 16597531
TI  - Peripherally acting mu-opioid-receptor antagonists and the connection between
      postoperative ileus and pain management: The anesthesiologist's view and beyond.
AB  - The adverse effects of opioids are well documented. Because opioid receptors have
      a wide-ranging anatomic distribution, the effects subsequent to opioid binding,
      both good and bad, occur centrally and in the periphery. Postoperative strategies
      to reduce opioid burden, therefore, are in the patient's best interest.
      Multimodal analgesia is the key towards balancing the need for opioids while
      simultaneously reducing their burden. Alternative anesthesia and analgesia
      options such as regional anesthesia, nonsteroidal anti-inflammatory drugs, or
      cyclooxygenase-2 enzyme inhibitors should be considered part of multimodal
      protocols. Familiarity of where these drugs are active in the body and how they
      can be employed is imperative for all surgical team members. Optimal
      implementation of multimodal approaches can reduce hospital stay and improve
      clinical outcomes, including patient satisfaction. Finally, strategies that may
      help reduce rates of hospital readmission also contribute to overall improved
      outcome. New peripherally acting mu-opioid-receptor antagonists represent
      significant progress in the ability of perianesthesia nurses to play an even
      greater role in achieving these goals. In contrast to older opioid-receptor
      antagonists, these agents specifically target an important aspect of the
      multifactorial etiology of postoperative ileus (POI), mu-opioid-receptor-mediated
      activity in the GI tract. In addition, they do not pass the blood-brain barrier
      or diminish opioid-mediated analgesia. Advanced clinical trials have already
      demonstrated the ability of one of these agents, alvimopan, to reduce POI and
      improve other postoperative outcomes while maintaining adequate analgesia.
      Combined with other options aimed at reducing opioid burden, alvimopan and
      similar drugs in development hold promise as part of multimodal protocols to
      optimize pain management while minimizing postoperative morbidities.

PMID- 16597533
TI  - Nurses are everywhere: a practical perspective on the surgical team in managing
      postoperative ileus.
AB  - Because the availability of new, peripherally acting mu-opioid-receptor
      antagonists is expected soon, it is important for all members of the surgical
      team to familiarize themselves with new approaches and also re-evaluate older
      approaches to help improve patient outcomes. "Preop nurses" have numerous
      responsibilities, among which are mitigating some of the adverse outcomes of
      surgery such as postoperative ileus (POI), making these nursing personnel
      indispensable to the proper implementation of multimodal management protocols for
      POI. Establishing basic preoperative procedures is an important primary
      consideration. Preoperative evaluation of general health, medical history
      (including surgical history), and an assessment of gastrointestinal (GI) function
      and habits should all be part of careful up-front assessment for each patient,
      especially because POI and other GI adverse effects are so often encountered in
      the PACU. Hand-in-hand with how we as nurses interact with our surgical
      colleagues is patient education regarding hospitalization and postrecovery
      expectations. PACU nurses will be key players in maintaining proper
      implementation of multimodal regimens, essentially doing this in two "phases":
      Phase I interventions comprise the ongoing assessment and monitoring of patients,
      administering medications, and evaluating patient satisfaction and overall
      status; Phase II considerations encompass a further set of practice guidelines
      that center on optimizing discharge status, including pain management and
      education as well as other discharge needs. Where new agents may fit into
      multimodal regimens that optimally incorporate preoperative and postanesthesia
      protocols remains to be determined. What is clear is that as nurses and the
      entire surgical team strive to enhance patient satisfaction, nursing personnel
      must assume leadership roles in how new multimodal strategies are implemented and
      executed. Advanced clinical data for the new peripherally acting mu-opioid
      receptor antagonist alvimopan, and for the drug class as a whole, have
      contributed to a greater impetus on reassessing perioperative protocols and
      policy, helping to broach innovative clinical frontiers of how we treat pain and
      POI, and thus improve patient outcomes.

PMID- 16597535
TI  - Treatment of Vogt-Koyanagi-Harada disease by corticosteroids and
      immunosuppressive agents.

PMID- 16597534
TI  - Current choices--good or bad--for the proactive management of postoperative
      ileus: A surgeon's view.
AB  - Postoperative ileus (POI) is frequently experienced by many patients undergoing
      abdominal operations and other surgical procedures. Postoperative ileus causes
      physical discomfort and may increase risk for prolonged hospital length of stay.
      Despite its prevalence, there is currently no accepted standard definition of POI
      and, consequently, no standardized mode of prevention or treatment; it is no
      wonder that a variety of management approaches for POI have been developed. Some
      of these include alternative surgical techniques such as laparoscopic or
      endoscopic procedures to minimize trauma and help lessen the release of
      endogenous mediators of POI. Others have evaluated alternate analgesic regimens
      such as thoracic epidural anesthetics to avoid stimulating opioid receptors in
      the gut. These approaches have had varying results. Other pharmacologic attempts
      to reduce POI have focused on the blockade of opioid receptors to prevent opioid
      induced GI-related adverse effects. A new class of agents, peripherally acting mu
      opioid-receptor antagonists such as methylnaltrexone and alvimopan, may improve
      the pharmacologic management of POI and reshape the current paradigm of
      multimodal management of POI. Protocols that incorporate these agents may offer
      yet another avenue to mitigate the adverse effects of POI, and thus help improve
      surgical outcomes. To date, alvimopan has been shown in phase 3 clinical trials
      to significantly reduce the duration of POI while maintaining satisfactory
      analgesia and reducing length of hospital stay. Combinations of strategies with
      demonstrated effectiveness such as early feeding, epidural analgesia,
      laparoscopic surgery, and peripherally acting mu-opioid-receptor antagonists may
      help transform the management of POI into an effective multimodal paradigm that
      targets the diverse etiologic factors leading to this common clinical problem.
      Clearly, all surgical team members are crucial in the optimal implementation of
      such multimodal approaches.

PMID- 16597536
TI  - The pros and cons of intravitreal triamcinolone injections for uveitis and
      inflammatory cystoid macular edema.
AB  - Intravitreal triamcinolone acetonide (IVTA) injections are gaining in popularity
      and are regularly administered nowadays for various ocular diseases. This paper
      presents a literature review on the use, efficacy, and complications of IVTA
      application in non-infectious uveitis and inflammatory cystoid macular edema
      (CME). In addition, we describe the experiences of our own institute. IVTA
      applications brought about a quick improvement in vision in the majority of
      cases. Drawbacks included the temporary duration of the effect with the need for
      repeated injections which re-exposed patients to the risk of complications. The
      risk of bacterial endophthalmitis was 0.5% and was further influenced by the
      specific IVTA preparation. Based on the literature review, we chose ready-for-use
      IVTA injections prepared by our pharmacy department, in which 90% of the toxic
      additives were removed and the dispensed dose of triamcinolone acetonide was
      validated to diminish the risk of endophthalmitis. Elevated intraocular pressure
      (IOP) was seen in 30-43% of the eyes and cataract developed in 29% of the eyes of
      patients, who were usually of advanced age. In conclusion, the rapid effect of
      IVTA might be of value in severe presentations of non-infectious uveitis and CME
      and might shorten the time interval needed for the improvement.

PMID- 16597537
TI  - Immunomodulatory therapy for Vogt-Koyanagi-Harada patients as first-line therapy.
AB  - PURPOSE: To report on the use of immunomodulatory therapy (IMT) in a group of
      patients with Vogt-Koyanagi-Harada disease (VKH) and to compare the outcomes with
      those of another group of patients with VKH who were treated for prolonged
      periods with corticosteroids. METHODS: Treatment regimens and their respective
      outcomes (visual acuity) were compared for the following groups: prolonged
      steroid with or without delayed addition of IMT (Group 1) and relatively prompt
      IMT with or without steroid (Group 2). RESULTS: The average duration of follow-up
      in Group 1 was 28.9 months and in Group 2 23.4 months. In Group 1, visual acuity
      deteriorated in three of the five patients (60%) and improved in one (20%). The
      fifth patient showed improvement in visual acuity in one eye, but decreased
      visual acuity in the other eye. In Group 2, seven of the eight patients showed
      improvement in their visual acuities (87.5%); visual acuity deteriorated in one
      patient (12.5%). CONCLUSIONS: The results suggest that IMT as first-line therapy
      for VKH is associated with a superior visual outcome when compared to steroid as
      monotherapy or with delayed addition of IMT.

PMID- 16597538
TI  - Management of pediatric Vogt-Koyanagi- Harada (VKH)-associated panuveitis.
AB  - PURPOSE: To assess the clinical course, determine the efficacy and safety of oral
      methotrexate in the control of intraocular inflammation, and evaluate the
      outcomes of lensectomy-vitrectomy and goniosynechiolysis on pediatric VKH
      associated panuveitis. DESIGN: Retrospective non-comparative interventional case
      series. PARTICIPANTS: Ten patients (20 eyes) with pediatric VKH-associated
      panuveitis (onset of disease at age 14 years or younger). INTERVENTION: Stepwise
      medical treatment consisted of oral prednisolone (0.5-1 mg/kg), supplemented by
      oral methotrexate (5-7.5 mg/wk) in refractory cases. Surgical intervention was
      performed for complications such as visually significant cataracts and secondary
      glaucoma and included pars plana lensectomy-vitrectomy and peripheral anterior
      synechiolysis in a one-stage procedure. MAIN OUTCOME MEASURES: Control of
      inflammation, corticosteroid requirement, visual acuity, and intraocular pressure
      (IOP). RESULTS: Ten consecutive patients with a minimum follow-up duration of six
      months were analyzed. All patients were initially treated with oral
      corticosteroids; methotrexate was additionally required in six subjects. In all
      eyes, inflammation decreased and vision was preserved or improved. Side effects
      of methotrexate were mild and transient. Nine eyes of five patients underwent
      combined lensectomy and vitrectomy. The procedure was successful in all eyes
      without any exacerbation of inflammation. Eight eyes had elevated IOP, six of
      which underwent peripheral anterior synechiolysis at the time of lensectomy
      vitrectomy. IOP was controlled after the procedure in all eyes with timolol only.
      Overall, final visual acuity was=20/40 in 30% of the eyes and<20/200 in only 20%.
      CONCLUSIONS: Pediatric VKH-associated panuveitis seems to follow an aggressive
      course; the development rate of cataracts and secondary glaucoma seems to be
      high. Oral methotrexate is a safe and effective adjunct and displays steroid
      sparing properties in the control of inflammation. Surgical interventions
      including peripheral anterior synechiolysis in addition to pars plana lensectomy
      and vitrectomy may be effective in controlling IOP in eyes with cataract and
      glaucoma. PRECIS: Vision may be preserved in pediatric VKH panuveitis using
      steroids and methotrexate for the control of inflammation, lensectomy-vitrectomy
      for visual improvement, and synechiolysis for IOP control.

PMID- 16597539
TI  - Patterns of exacerbations of chronic non-infectious uveitis in pregnancy and
      puerperium.
AB  - PURPOSE: To determine patterns of exacerbations of recurrent non-infectious
      uveitis during pregnancy and puerperium. DESIGN: Retrospective cohort study.
      METHODS: The medical records of 32 women with a history of chronic non-infectious
      uveitis, who were pregnant during their follow-up at the Ocular Immunology and
      Uveitis Service of the Massachusetts Eye and Ear Infirmary, from 1983 through
      2003, were reviewed. The uveitis relapse rate during pregnancy was compared to
      the relapse rate during pregnancy-free periods in these women and to the relapse
      rate in a control group of women of childbearing age with recurrent non
      infectious uveitis. RESULTS: Among the 32 women who were pregnant during follow
      up (40 pregnancies), the rate of flare-ups during pregnancy (1.0 recurrence per
      year) was lower than that observed during non-pregnant periods (2.4 per year;
      p<0.001) and lower than that observed in the non-pregnant control group (3.1 per
      year; p<0.001). Flare-ups were most frequent in the first trimester of pregnancy
      and decreased markedly in the second and third trimesters (2.3, 0.5, and 0.4
      recurrences per year, respectively; p<0.001). CONCLUSIONS: Pregnancy is
      associated with lower numbers of flare-ups of non-infectious uveitis compared to
      the non-pregnant state. If flare-ups do occur during pregnancy, they happen
      predominantly in the first trimester.

PMID- 16597540
TI  - Diagnostic value of specific local antibody production and nucleic acid
      amplification technique-nested polymerase chain reaction (nPCR) in clinically
      suspected ocular toxoplasmosis.
AB  - OBJECTIVE: The study was to evaluate the diagnostic efficacy of nested polymerase
      chain reaction (nPCR) using primers targeting B1 gene of Toxoplasma gondii (T.
      gondii) with Witmer Desmonts coefficient (WDC) technique in intraocular fluids of
      clinically suspected toxoplasma retino choroiditis (TRC) patients. MATERIALS AND
      METHODS: Two hundred and seventy eight specimens from 189 patients (25 TRC
      patients and 164 controls) consisting of 189 serum samples and 89 intraocular
      fluids were included in the study. The clinical specimens were categorized into
      TRC patients (typical TRC lesion-group I & atypical TRC lesion-group II) and
      controls (voluntary blood donors-group III, patients undergoing uncomplicated
      cataract surgery-group IV, ocular inflammation of non-toxoplasma origin-group V).
      Detection of anti T. gondii IgG and IgM antibodies in serum samples and
      intraocular fluids were performed and WDC was calculated by the standard method.
      The standardized nPCR was applied on the 89 intraocular fluids. RESULTS: Clinical
      diagnosis of TRC based on fundus examination was considered to be the "gold
      standard." Anti T. gondii IgG/IgM antibodies were detected in serum by ELISA in
      95.6% of 25 clinically suspected TRC patients (gp I and II), 28% of gp III, 40.4%
      of gp IV, and in 58.3% of gpV. Witmer Desmont's coefficient was positive in 72.7%
      (16/22) and nPCR in 59.1% (13/22) of TRC patients (gp I and II). Both WDC and
      nPCR were negative in all the controls. The difference in sensitivity of WDC and
      nPCR was not statistically significant (p=0.5247). CONCLUSIONS: Though both WDC
      and nPCR were reliable diagnostic techniques for ocular toxoplasmosis, nPCR is
      more acceptable because of the amount of specimen(s) required, rapidity, cost
      effectiveness, and direct evidence of T. gondii DNA in the intraocular fluids.

PMID- 16597541
TI  - Decreased platelet membrane fluidity in retinal periphlebitis in Eales' disease.
AB  - PURPOSE: Oxidative damage to cellular membranes plays an important role in the
      pathobiology of tissue injury. Free radical-induced peroxidation of membrane
      lipid and protein is associated with alterations in cellular, morphological,
      biochemical, and physical dynamics, which are related to the mobility of lipid
      molecules. Retinal photoreceptors and platelets have been shown to be an easy
      target of oxidants because of their high proportion of polyunsaturated fatty
      acids. This study was undertaken, for the first time, to investigate membrane
      fluidity in the platelets of patients with Eales' disease. METHODS: Assays of
      malonaldialdehyde levels and the enzymes superoxide dismutase and catalase and
      fluorescence polarization, for estimating membrane fluidity, were carried out on
      platelets from 20 patients with Eales' disease (stage 1 characterized by
      periphlebitis of small (1a) and large (1b) caliber vessels with superficial
      retinal hemorrhages) and 15 healthy controls. RESULTS: A significant increase was
      observed in the malonaldialdehyde levels. A significant decrease in the activity
      of superoxide dismutase and catalase was also observed. Platelet fluorescence
      polarization was significantly higher in the patients, indicating decreased
      membrane fluidity compared to controls (p<0.01). CONCLUSION: A decrease in
      platelet membrane fluidity occurs as a result of oxidative stress in retinal
      periphlebitis in Eales' disease. The decreased membrane fluidity suggests
      alterations in the physiological events, which may result in alterations in the
      functioning of retinal photoreceptors.

PMID- 16597542
TI  - Age as a determinant factor for endotoxin induced uveitis.
AB  - PURPOSE: To determine if susceptibility to systemic endotoxin-induced uveitis is
      an age-related phenomenon in the rabbit. METHODS: Young and adult rabbits were
      injected intravenously with 2.5 microg/kg of E. coli endotoxin or saline.
      Thereafter, the number of exudating cells at 2, 6, 12, 24 and 48 hours were
      determined. The levels of lipopolysaccharide-binding protein, total protein,
      prostaglandin-E2, nitric oxide and interleukin-6 in aqueous humor were also
      determined 24 hours after the injections. RESULTS: A significant increase in the
      number of exudating cells and the levels of lipopolysaccharide-binding protein,
      total protein, prostaglandin-E2 and nitric oxide in aqueous humor was observed
      only in adult rabbits 24 hours after endotoxin injection. No differences were
      observed in the increased IL-6 levels. CONCLUSIONS: Life stage seems to be a
      critical factor in developing an eye-inflammatory response induced by systemic
      endotoxin. This could be a consequence of a differential specific activation of
      the ocular immune response.

PMID- 16597543
TI  - Atopic optic neuritis.
AB  - PURPOSE: To report a case of optic neuritis associated with atopic dermatitis,
      which may represent an optic nerve counterpart of atopic myelitis. METHODS:
      Clinical examination, MRI, blood investigations. RESULTS: A 34-year-old man with
      severe atopic dermatitis developed a steroid-responsive bilateral optic neuritis.
      Serum IgE was highly elevated, with high titers of mite-specific IgE. Clinical
      ophthalmological fluctuations paralleled those of atopic dermatitis. CONCLUSIONS:
      The clinical features and parallel fluctuations strongly suggest that the
      patient's optic neuritis was related to atopic dermatitis. This atopic optic
      neuritis may represent the optic nerve equivalent of atopic myelitis.

PMID- 16597544
TI  - Polymicrobial keratomycosis in a three-year-old child.
AB  - PURPOSE: To describe a previously unreported case of polymicrobial mycotic
      keratitis caused by an association between Candida lusitaniae, C. parapsilosis,
      and Geotrichum candidum. METHODS: A three-year-old child with an antecedent
      trauma with vegetable matter and a prolonged use of corticosteroid eyedrops
      developed fungal keratitis. RESULTS: The isolates of the corneal scraping using
      Sabaraud dextrose agar grew C. lusitaniae, C. parapsilosis, and G. candidum.
      After topical 0.2% and systemic fluconazole treatment, the corneal lesion
      resolved with no recurrence. CONCLUSIONS: Corneal trauma with vegetables and the
      indiscriminate use of corticosteroids are important risk factors for mycotic
      keratitis. A combination of topical 0.2% and systemic fluconazole therapy was
      effective in the treatment of this mycotic association. This is the first report
      of fungal keratitis caused by C. lusitaniae and G. candidum.

PMID- 16597546
TI  - Hearing aid technology and benefit.

PMID- 16597549
TI  - A one-year neonatal mouse carcinogenesis study of quinacrine dihydrochloride.
AB  - Quinacrine is an acridine derivative under investigation for its use in
      nonsurgical female sterilization. Safety issues regarding the carcinogenic
      potential of quinacrine have been raised because it is mutagenic and clastogenic
      in vitro. The objective of the study was to evaluate the carcinogenic potential
      of quinacrine dihydrochloride (quinacrine) in neonatal mice treated with single
      intraperitoneal doses on postpartum days 8 and 15 and observed for 52 weeks.
      Neonatal Crl: CD-1 mice of each sex were randomly allocated into four treatment
      groups (0, 10, 50, and 150 mg/kg), dosed twice with quinacrine suspended in
      carboxymethylcellulose, observed for 52 weeks post dose, and then euthanized,
      necropsied, and subjected to a full histopathological examination. In male mice,
      tumor incidence was not significantly increased at any site at any dose level. In
      female mice, the incidence of benign uterine endometrial stromal polyps was
      slightly greater at the mid and high dose (> or = 50 mg/kg), as was the incidence
      of endometrial hyperplasia. The incidence of polyps in these groups was not
      significantly greater than in controls by pair-wise comparison but was
      significantly greater (p = .042) by the linear trend test. The authors conclude
      that quinacrine administered twice to neonatal mice may have enhanced or
      accelerated the development of endometrial hyperplasia and uterine stromal polyps
      at higher doses. Because uterine stromal polyps are a commonly observed benign
      tumor in older mice, the significance of this finding is unclear and will require
      a weight of evidence evaluation for a conclusion on the carcinogenic potential of
      quinacrine.

PMID- 16597548
TI  - Modeling aggregate exposures to glycol ethers from use of commercial floor
      products.
AB  - Computer modeling of aggregate exposure provides the capability to estimate the
      range of doses that can occur from product use and to understand the relative
      importance of different routes of exposure. This paper presents an assessment of
      aggregate occupational exposure to two glycol ethers used as solvents in floor
      maintenance products for industrial and institutional facilities, using a
      simulation tool named PROMISE. Three commercial floor-care products were assumed
      to be applied in sequence--a floor stripper, then a floor cleaner, and lastly a
      protective coating. The glycol ethers modeled were ethylene glycol butyl ether
      (EGBE) in the floor stripper and in the floor cleaner, and dipropylene glycol
      methyl ether (DPGME) in the coating. Modeling uncertainty was assessed through a
      comparison of the PROMISE inhalation exposure estimates with those from an
      independent model (MCCEM), and parameter uncertainty was investigated using
      PROMISE software's Monte Carlo simulation capabilities. Modeling results
      indicated that inhalation is the dominant exposure route. The predicted average
      air concentration and inhalation dose from PROMISE agreed with the second model
      (MCCEM) within 10%. Monte Carlo simulation indicated that the upper end of the
      aggregate-dose distribution for the scenario was more than 50% higher than the
      value of the point estimate. The modeled 8-h TWA concentrations for EGBE and
      DPGME were lower than the corresponding permissible exposure limits American
      Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Values
      (TLV) by at least a factor of 20, indicating that under the assumed conditions
      workplace exposures to glycol ethers are below levels of concern.

PMID- 16597547
TI  - Gene expression analysis of troglitazone reveals its impact on multiple pathways
      in cell culture: a case for in vitro platforms combined with gene expression
      analysis for early (idiosyncratic) toxicity screening.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists of the
      thiazolidinedione family are used for the treatment of type 2 diabetes mellitus
      due to their ability to reduce glucose and lipid levels in patients with this
      disease. Three thiazolidinediones that were approved for treatment are Rezulin
      (troglitazone), Avandia (rosiglitazone), and Actos (pioglitazone). Troglitazone
      was withdrawn from the market due to idiosyncratic drug toxicity. Rosiglitazone
      and pioglitazone are still on the market for the treatment of type 2 diabetes.
      The authors present data from a gene expression screen that compares the impact
      these three compounds have in rats, in rat hepatocytes, and in the clone 9 rat
      liver cell line. The authors monitored the changes in expression in multiple
      genes, including those related to xenobiotic metabolism, proliferation, DNA
      damage, oxidative stress, apoptosis, and inflammation. Compared to the other two
      compounds, troglitazone had a significant impact on many of the pathways
      monitored in vitro although no major perturbation was detected in vivo. The
      changes detected predict not only general toxicity but potential mechanisms of
      toxicity. Based on gene expression analysis, the authors propose there is not
      just one but multiple ways troglitazone could be toxic, depending on a patient's
      environment and genetic makeup, including immune response-related toxicity.

PMID- 16597550
TI  - Safety assessment of 4'-thio-beta-D-arabinofuranosylcytosine in the beagle dog
      suggests a drug-induced centrally mediated effect on the hypothalamic-pituitary
      adrenal axis.
AB  - 4'-Thio-beta-D-arabinofuranosylcytosine (OSI-7836) is a nucleoside analogue with
      structural similarity to gemcitabine and cytarabine (ara-C). Myelosuppression,
      reversible transaminase elevations, and flu-like symptoms are common side effects
      associated with human use of gemcitabine and ara-C. Fatigue is also associated
      with the use of gemcitabine and OSI-7836 in humans. To better understand the
      toxicity of OSI-7836, subchronic studies were conducted in dogs. OSI-7836 was
      administered on days 1 and 8 or on days 1, 2, and 3 of a 21-day dose regimen.
      These schedules attempted to match clinical trial dosing regimens. Routine
      toxicity study end points demonstrated that OSI-7836 was primarily cytotoxic to
      the gastrointestinal tract, bone marrow, and testes; the myelotoxicity was mild
      and reversible. Plasma pharmacokinetics were dose-linear with an elimination half
      life of 2.2 h. Follow-up single dose experiments in dogs assessed drug effects on
      lymphocyte subpopulations and on adrenal and thyroid function. Populations of T
      and B cells were equally reduced following OSI-7836 administration. There were no
      adverse effects on thyroid function, but there were marked reductions in
      circulating cortisol and adrenocorticotropic hormone concentrations suggesting a
      centrally mediated impairment of the hypothalamic-pituitary-adrenal axis. These
      findings show a toxicological profile with OSI-7836 similar to other nucleoside
      analogues and suggest that the beagle is a model for studying one possible cause
      of OSI-7836-related fatigue, impaired function of the hypothalamic-pituitary
      adrenal axis.

PMID- 16597557
TI  - Barriers to the consumption of fruits and vegetables among older adults.
AB  - Compared with younger adults, older people experience additional health, social,
      and environmental conditions that affect their dietary intake. To identify those
      additional dimensions and examine them in association with fruit and vegetable
      intake, data of 4,622 participants in NHANES III (1988-1994), ages 60 years and
      over, were analyzed using multivariate logistic regression modeling. Results
      showed that participants at highest risk of consuming fruits and vegetables in
      the lowest quartile were those socially isolated, with missing pairs of posterior
      teeth, with poor self-reported health and those who were obese. To prevent
      downward spiraling health, barriers must be addressed in intervention programs.

PMID- 16597551
TI  - Evaluation of the developmental toxicity of alpha-methyl-3,4-methylene
      dioxyhydrocinnamic aldehyde in rats.
AB  - The developmental toxicity of alpha-methyl-3,4-methylene-dioxyhydrocinnamic
      aldehyde (MMDHCA), a widely used fragrance ingredient, was evaluated for
      developmental toxicity in Sprague-Dawley rats (25/group; cesarean-sectioning
      identified 21 to 25 pregnant rats/group). Oral dosages of 0 (corn oil), 62, 125,
      or 250 mg/kg/day were administered by gavage on days 7 through 17 of gestation
      (GDs 7 through 17). Rats were observed for viability, clinical signs, body
      weights, and feed consumption. Necropsy and cesarean sectioning occurred on GD
      21. Uteri were examined for number and distribution of implantations, live and
      dead fetuses, and early and late resorptions. Numbers of corpora lutea were also
      recorded. Fetuses were weighed and examined for gender, gross external changes,
      and soft tissue or skeletal alterations. Analysis of dosage preparations verified
      calculated dosages +/-10%. No deaths occurred. Excessive salivation occurred in
      all groups, but the incidence was increased at 250 mg/kg/day. The 250 mg/kg/day
      dosage also was associated with a significant increase in the incidences of a
      clear, red or yellow perioral and/or red perivaginal substance and significant
      reductions in mean feed consumption and body weight gains (11.6% and 7.4%,
      respectively) during the entire dosage period. No gross changes attributable to
      MMDHCA were observed at necropsy. Cesarean section or litter parameters, as well
      as fetal alterations, were not affected by MMDHCA at 250 mg/kg/day or either of
      the lower dosages tested. Based on these data, maternal and developmental no
      observable-effect levels (NOAELs) of 125 and >250 mg/kg/day, respectively, were
      established for MMDHCA. It is concluded that MMDHCA is not a developmental
      toxicant in rats under the conditions of this study and dosing regimen.

PMID- 16597558
TI  - Relation between C-reactive protein and serum and dietary antioxidants in older
      adults at increased risk for cardiovascular disease.
AB  - The purpose of this study was to determine the relation between serum and dietary
      antioxidants, and C-reactive protein (CRP) concentrations in middle-aged and
      older individuals at risk for cardiovascular disease. We used data from adults
      aged > or = 40 at increased risk for cardiovascular disease selected from the
      NHANES III database. The relation between serum and dietary antioxidants, and CRP
      concentrations was examined using multiple logistic regression analysis. Serum
      antioxidants and CVD risk factors were significant predictors of detectable CRP
      concentrations (R2 = 0.07; p < 0.001). Dietary antioxidants (except vitamin C)
      were not significant predictors of detectable CRP concentrations.

PMID- 16597560
TI  - Diuretic medication therapy use and low thiamin intake in homebound older adults.
AB  - Diuretic therapy (DT) plays a major role in disease management. However, one
      issue of concern in nutritionally vulnerable elders is that diuretic therapy also
      increases thiamin excretion, and little attention has been paid to the linkage
      between DT use and dietary intake of thiamin in this older population. The
      purpose of this study was to assess the relationship between DT use and dietary
      intake of thiamin in a randomly recruited sample of 342 homebound older adults.
      Baseline data, including three 24-hour recalls, were used to identify thiamin
      intake from food (15% < EAR and 33% < RDA), DT use (49%), and meal pattern (18%
      not regularly eating breakfast). Independent of sociodemographic and meal pattern
      variables, DT users (relative to non-users) were at increased odds for dietary
      thiamin intake < RDA (OR = 2.3) and < EAR (OR = 4.2). Considering the importance
      of home-delivered meals as a primary source of food assistance to homebound
      elders and that thiamin deficiency may exacerbate health problems, the results of
      this study suggest the need to include information on DT use as an integral
      component of program assessment for the targeting and monitoring of strategies to
      alleviate the risk for deficiency.

PMID- 16597559
TI  - Organizational issues related to satisfaction with food and food service in the
      nursing home from the resident's perspective.
AB  - This paper reviews organizational factors that potentially affect food quality
      and food service in the nursing home. A model is proposed for assessing the
      influence of organizational technology on resident satisfaction with food and
      food service from the resident's perspective. Findings from an exploratory
      phenomenological case study applying the model are presented. Staff knowledge of
      how to prepare and serve food properly, and staff availability to serve food on
      time, were key constructs. Resident-staff interactions appeared to moderate
      resident control over food and food service. Recommendations are suggested for
      improved communication between residents and staff to address certain limitations
      and enhance empowerment of residents.

PMID- 16597567
TI  - Integrated care could have helped with 9/11.

PMID- 16597561
TI  - Kosher meal services in the community:need, availability, and limitations.
AB  - This project identified needs and barriers for Meals on Wheels and other
      nutrition programs serving kosher meals. Responses to a national survey indicated
      that some communities met their need for kosher meal services, others had
      difficulty keeping up with the demand and costs of providing these meals. The
      primary need for kosher meal services was in metropolitan areas where large
      communities of orthodox Jews observe kosher dietary laws. Knowledge about kosher
      dietary laws and lack of reasonably priced kosher meals were two main problems.
      Service providers need economical sources for kosher meals as well as financial
      support to offset the higher cost of these meals. Providers should work with
      local Jewish community organizations to determine what the actual need may be,
      whether it is simple dietary modifications or kosher meals.

PMID- 16597568
TI  - The impact of 9/11 on New York City's substance abuse treatment programs: a study
      of program administrators.
AB  - Given the far-reaching effects of the terrorist attacks on September 11, 2001, a
      study was conducted under the supervision of the New York State Office of
      Alcoholism and Substance Abuse Services to assess the impact on New York City's
      substance abuse treatment programs. A stratified, random sample of 15 treatment
      programs was selected to represent the system's major modalities. Administrators
      representing these programs were interviewed face-to- face using a structured
      interview schedule. The questions mainly probed the problems experienced on 9/11
      and afterwards, patient issues and the lessons learned. The findings show major
      concerns for the mental health of both staff members and patients, the failure of
      the telephone communication system, the particular sensitivity of drug-free
      outpatient clinics, the challenges experienced by methadone programs, and the
      need to update disaster planning. A host of problems came to the fore now
      requiring another level of thinking.

PMID- 16597569
TI  - Fentanyl abuse and dependence: further evidence for second hand exposure
      hypothesis.
AB  - We have proposed a novel hypothesis regarding the potential role of occupational
      or second-hand exposure in physician substance use, abuse, and addiction. While
      only 5.6% of licensed physicians in Florida are anesthesiologists, nearly 25% of
      physicians followed for substance abuse/dependence are anesthesiologists. When we
      sort by drug of choice, anesthesiologists have more opioid abuse and dependence
      than other physicians and appropriate controls. Abuse of one opioid, fentanyl,
      appears to be increasing and has been noted among the State of Florida's causes
      of opioid deaths. Fentanyl and sufentanyl are commonly administered highly potent
      opioid analgesics, as much as 80-800 times as potent as morphine. We have recent
      data from the State of Florida impaired physicians database, which has allowed us
      to categorize all fentanyl abusing and/ or dependent physicians. Just knowing
      that a physician abuses fentanyl gives you a good clue as to their specialty; 75%
      are anesthesiologists! While drug abuse researchers, oncologists and others who
      handle drugs of abuse everyday, have no greater incidence of opioid abuse or
      dependence, anesthesiologists are at the top of every list. Can this be due to
      just access and stress? We have proposed an alternative hypothesis of second hand
      exposure. To test this hypothesis, we developed a sensitive LC/MS/MS assay to
      measure the intravenous anesthetic and analgesic agents, propofol and fentanyl in
      air. Not only did we detect propofol and fentanyl in cardiovascular surgery
      operating room air, we also found the highest concentrations were close to the
      patient's mouth where anesthesiologists work for hours. Like tobacco, second hand
      opioid exposure can sensitize and change the brain making abuse, dependence and
      behavioral disorders more likely. Thus environmental exposure and sensitization
      may be an important risk factor in physician addiction. Second hand exposure may
      affect treatment outcome and explain anesthesiologist's inability to return to
      work in the operating room. We are developing an animal model for second hand
      exposure and additional studies of the operating room and cardiac
      anesthesiologists are underway.

PMID- 16597570
TI  - Combined buprenorphine and chlonidine for short-term opiate detoxification:
      patient perspectives.
AB  - The approval in 2003 for the use of buprenorphine in opiate addiction treatment
      has provided physicians with a new pharmacological tool to combat opiate
      addiction. We surveyed a sample of 100 inpatients who completed short-term opiate
      detoxification treatment utilizing a combination of buprenorphine and clonidine
      to assess patient perspectives regarding the usefulness and tolerability of this
      medication regimen and to compare it to their past opiate detox experiences, if
      any. Patients identified pain (63%), sleep problems (57%), and anxiety (56%) as
      the symptoms they perceived to be most helped with buprenorphine. Over 90% of
      patients with past detoxification treatments rated buprenorphine treatment to be
      as good as or better than their past treatments. Reports of a euphoric effect
      were minimal (7%) and no patients reported any generalized worsening of their
      opiate withdrawal symptoms. We conclude that based upon patient perspectives that
      combining buprenorphine with clonidine is a useful and well-tolerated medication
      regimen for the treatment of opiate withdrawal.

PMID- 16597571
TI  - Severity of dependence and motivation for treatment: comparison of marijuana- and
      cocaine-dependent treatment seekers.
AB  - Although marijuana dependence is prevalent, most individuals with marijuana
      dependence do not seek treatment. There are few data characterizing treatment
      seeking marijuana-dependent patients compared to patients presenting for
      treatment of other drugs regarding the severity of illness and motivation for
      treatment. Forty-two marijuana-dependent individuals were compared to 58 cocaine
      dependent individuals seeking treatment. Compared to cocaine-dependent patients,
      those with marijuana dependence were younger and less likely to be dependent on
      alcohol or other drugs. Both groups had similar rates of comorbid anxiety and
      affective disorders. Marijuana-dependent individuals had lower total number of
      dependence symptoms but had a higher percentage of individuals endorsing
      withdrawal symptoms. Although marijuana-dependent individuals had less outpatient
      treatment exposure, the difference between the two groups was not significant and
      motivation for change, based on the University of Rhode Island Change Assessment,
      was similar for both groups of treatment seekers. However, the Circumstances,
      Motivation, Readiness for Treatment Scale suggested that cocaine-dependent
      individuals were more motivated for treatment. Taken together, these data suggest
      that treatment seeking marijuana-dependent individuals have substantial
      withdrawal dependence symptomatology although it is less clear if they are as
      motivated to seek out treatment as cocaine-dependent treatment seekers.

PMID- 16597573
TI  - Physical trauma and substance abuse: a comparative study on substance abuse in
      patients with physical trauma versus general population.
AB  - AIM: To evaluate the prevalence of substance abuse in a sample of patients with
      acute physical trauma in comparison with the general population. METHOD:
      Prospective study using structured interview based on DSM-IV (Diagnostic and
      Statistical Manual of Mental Disorders, 4th ed) criteria for substance dependence
      and abuse. SETTING: Hospitals at Shiraz University of Medical Sciences, and the
      general population in Shiraz. PARTICIPANTS: 1,324 subjects selected randomly (324
      subjects from patients with acute physical trauma, and 1,000 subjects from
      general population). RESULTS: The mean age was 37 (SD=15.5, age range=15-83 yr.)
      In the general population, the mean age was 36.5 (SD=14.29, age range=15-83).
      Substance use was much more prevalent among patients with acute physical trauma
      than in the general population. It should be mentioned that drug use precedes the
      trauma in the patient population and may contribute to the occurrence of trauma
      or disease. CONCLUSIONS: Substance use was significantly more prevalent in males
      than in females. Cultural attitudes toward usage of substances were found to
      affect the type and amount of the used substance. These findings should be
      considered when planning preventive and therapeutic programs.

PMID- 16597572
TI  - High methadone dose significantly reduces cocaine use in methadone maintenance
      treatment (MMT) patients.
AB  - AIM: To evaluate whether effective methadone treatment affects cocaine use.
      METHODS: 421 consecutive patients admitted to a methadone maintenance clinic in
      Israel (1993-2002) were prospectively studied. Patients' urine samples were
      analyzed for cocaine during months 1 and 13. RESULTS: On admission 55(13.1%) of
      421 patients had urine positive for cocaine and 366 had negative. Of the 55
      cocaine-positive patients, 45(81.8%) stayed in treatment at least one year, as
      did 267(73%) of cocaine-negative. After one year (n=312) 31 of 45 cocaine users
      stopped and 25 of 267 started. Methadone dose was highest in 31 patients who
      stopped cocaine (176.1+/-42.1 mg/ day), followed by 14 who did not stop (161.4+/
      37.5 mg/day), and 25 who started during treatment (122.9+/-48.7 mg/day), or 242
      who never used cocaine (119.5+/-48.4 mg/day) (ANOVA, F=15.6, p<0.0005).
      CONCLUSIONS: High methadone dose may reduce cocaine use in patients addicted to
      both heroin and cocaine.

PMID- 16597574
TI  - Prevention of relapse in the recovery of Arizona health care providers.
AB  - This project gathered survey information from physicians, physician assistants,
      dentists and pharmacists in Arizona who, while enrolled or following a completion
      of a monitored aftercare program, had relapsed back to active chemical
      dependency. The findings suggest several subjective factors that contributed to
      the subjects' relapse included (1) dishonesty to self, (2) not working a 12 step
      program, and (3) denial of the problem. Factors reported to be helpful for future
      relapse prevention were (1) abstinence from substance use, (2) working a 12 step
      program, and (3) having spiritual beliefs. In general, survey respondents were
      male, averaged 52 years of age, had relapsed several times and started abusing
      illicit drugs and alcohol in high school or college. By identifying the specific
      causes of relapse, future studies may attempt to decrease the percentage of
      health care providers who relapse by recognizing signs of problematic behavior
      before they occur.

PMID- 16597575
TI  - Utilization and outcomes of mental health services among patients in drug
      treatment.
AB  - This study examined utilization of mental health services and treatment outcomes
      among 1,091 patients with mental health problems recruited from 39 treatment
      programs in 13 California counties. We compared three groups: one that received
      dual treatment from drug and mental health programs (N=294), one that received
      mental health services only within drug treatment programs (N=578), and one that
      received no mental health services (N=219). Individuals who received dual
      treatment had more severe substance use and mental health problems, followed in
      severity by those who received mental health services within drug treatment, and
      those who received no services. All groups significantly reduced their
      psychiatric severity at the follow-up, although there were no group differences
      in treatment retention and drug use outcomes. These findings suggest that
      individuals with mental health problems can be successfully treated within drug
      treatment programs and/or in conjunction with mental health providers.

PMID- 16597576
TI  - Treatment readmissions and criminal recidivism in youth following participation
      in chemical dependency treatment.
AB  - The purpose of this study was to use administrative records of admissions to
      substance abuse treatment to construct episodes of care for publicly funded
      adolescent clients in Washington State, and then to analyze two important
      outcomes after an index episode: readmissions to treatment and criminal
      convictions (including felony convictions and any conviction). The study
      population was youth, ages 14 to 17, who began and ended an index episode in 1997
      and 1998 (n=5903). The youth were followed for 18 months after the end of their
      episode, and survival analysis techniques were used to determine the treatment
      correlates of the outcomes. Clients who completed treatment, compared to those
      who did not, had significantly lower risks of each outcome, while those with
      treatment episodes longer than 90 days had lower risks of readmission and felony
      convictions.

PMID- 16597577
TI  - Differences among those who complete and fail to complete inpatient
      detoxification.
AB  - Some individuals hospitalized for alcohol or drug detoxification leave against
      medical advice (AMA). We hypothesized that certain characteristics would be
      associated with AMA discharges. A case-control study of 1,426 hospital admissions
      for detoxification (representing 1,080 individuals) was conducted to compare
      patients leaving the hospital AMA (n=231) with a random sample of those
      completing detoxification (n=286). Latino ethnicity, detoxification from drugs,
      Friday or Saturday discharge, Medicaid or no health insurance, and not being
      treated by one specific attending physician were characteristics associated with
      an AMA discharge in a backward logistic regression model. Although 85% of the
      patients with all these characteristics left AMA, only one patient, without any
      of these five characteristics, did so. We conclude that clinicians can use
      certain clinical features to predict AMA discharge. Additional research could
      evaluate if treatment strategies that consider these ethnic and socioeconomic
      disparities may reduce rates of AMA discharge.

PMID- 16597578
TI  - Addiction treatment history, medical services utilization, and cost: a
      longitudinal analysis of problem drinkers.
AB  - Few studies have examined the long-term patterns of health services utilization
      and cost for alcohol use disorders. This paper used data from baseline, 3-year,
      and 5-year follow-up interviews to compare utilization and cost of medical care
      services for problem drinkers who received chemical dependence treatment and
      those who did not. The analysis examined overnight hospital stays, emergency room
      visits, and medical office visits. The unadjusted analysis indicates that in the
      year immediately preceding each follow-up period, a significantly higher
      percentage of the chemical dependency treatment group stayed overnight at a
      hospital or used ER services. In terms of medical office visits, a significantly
      lower percentage of the treatment sample had office visits at the 5-year follow
      up, but otherwise no significant differences existed. Most of the significant
      differences between the two groups vanished when we controlled for covariates.
      Researchers, policy makers, and clinicians could benefit from such information to
      develop alternative delivery models, formulate research initiatives, and
      determine areas for potential intervention and improvement.

PMID- 16597579
TI  - The long-term relationships between the motivation for change and alcohol use
      severity among patients with severe and persistent mental illness.
AB  - This study examined the long-term relationship of changes in the motivation to
      remedy alcohol abuse to alcohol use severity among patients with a dual diagnosis
      of substance abuse disorder and severe and persistent mental illness. Linear
      regression analyses showed that patients who increasingly recognized alcohol use
      problems over a 9-month period exhibited significantly greater alcohol use
      severity at 9 months and a significant increase in alcohol use severity over
      time. Moreover, patients who became increasingly determined to take actions
      against alcohol use over a 9-month period exhibited significantly lower alcohol
      use severity at 9 months and a significant decrease in alcohol use severity over
      time. The findings support Prochaska et al.'s transtheoretical model of the
      motivation for change. They suggest that the recognition of alcohol use problems
      comes along with learning adverse consequences of alcohol use and that increased
      determination to take actions is critical to the long-term behavioral changes in
      alcohol use.

PMID- 16597581
TI  - Participant satisfaction with the vocational rehabilitation process: a micro
      perspective of relationship dimensions.
AB  - This article is the last in a series of two that examines participant
      satisfaction with the vocational rehabilitation (VR) process. Disabled
      individuals face formidable challenges when entering the workforce. The VR
      process involves a complex series of interactions and relationships among
      participants, counselors, training professionals, ancillary service providers,
      and employers to help participants prepare for and find employment. In the first
      article, we identified six relationship dimensions that influence overall
      satisfaction with vocational training services and presented a highly reliable
      survey instrument. In part two, we look at the items within each dimension and
      identify those with the greatest impact on participant satisfaction. The findings
      show that the level of caring or concern demonstrated by the counselor, an
      element of the interpersonal social bond dimension, has the greatest affect on
      participant satisfaction with the entire VR process.

PMID- 16597582
TI  - Pharmaceutical drug marketing strategies and tactics: a comparative analysis of
      attitudes held by pharmaceutical representatives and physicians.
AB  - A variety of promotional strategies have been used to stimulate sales of
      pharmaceutical drugs. Traditionally, push techniques have been the predominant
      means used to encourage physicians to prescribe drugs and thus increase sales.
      Recently, the traditional push strategy has been supplemented by a pull strategy.
      Direct-to-consumer advertising is increasingly used to encourage consumers to
      request advertised drugs from their physicians. This research compares the
      attitudes of two of the most affected participants in the prescriptive sales
      processes; physicians and pharmaceutical sales representatives. The findings
      indicate differences between physicians and pharmaceutical sales representatives
      regarding the efficacy and ethical considerations of various promotional
      strategies.

PMID- 16597583
TI  - How well do direct-to-consumer, DTC, prescription drug web sites meet FDA
      guidelines and public policy concerns?
AB  - Direct-to-consumer drug advertising has increasingly become a focus of public
      policy concern and academic research. However, the Web has received very little
      of this attention. A content analysis of a sample of 90 complete DTC prescription
      drug Web sites examined whether the FDA's fair balance criteria are being met,
      how they are rated according to industry evaluation criteria, what impact they
      may have upon the patient-physician relationship, and how the content of these
      Web sites compares to that of print DTC ads. The study identified that a majority
      are meeting fair balance and adequate provision criteria, as well as several
      industry evaluative criteria. A comparison to print DTC reveals some strengths of
      the Web. Areas of continued concern include design elements and more information
      about supportive behaviors and competing/ alternative treatments.

PMID- 16597584
TI  - Physicians' decision process for drug prescription and the impact of
      pharmaceutical marketing mix instruments.
AB  - This paper provides an in-depth, qualitative analysis of the physicians' decision
      process for drug prescription. Drugs in the considered therapeutic classes are
      mainly prescribed by specialists, treating patients with obligatory medical
      insurance, for a prolonged period of time. The research approach is specifically
      designed to capture the full complexity and sensitive nature of the physician's
      choice behavior, which appears to be more hybrid and less rational in nature than
      is often assumed in quantitative, model-based analyses of prescription behavior.
      Several interesting findings emerge from the analysis: (i) non-compensatory
      decision rules seem to dominate the decision process, (ii) consideration sets are
      typically small and change-resistant, (iii) drug cost is not a major issue for
      most physicians, (iv) detailing remains one of the most powerful pharmaceutical
      marketing instruments and is highly appreciated as a valuable and quick source of
      information, and (v) certain types of non-medical marketing incentives (such as
      free conference participation) may in some situations also influence drug
      choices.

PMID- 16597586
TI  - An isochore map of human chromosomes.
AB  - Isochores are large DNA segments (>>300 kb on average) that are characterized by
      an internal variation in GC well below the full variation seen in the mammalian
      genome. Precisely defining in terms of size and composition as well as mapping
      the isochores on human chromosomes have, however, remained largely unsolved
      problems. Here we used a very simple approach to segment the human chromosomes de
      novo, based on assessments of GC and its variation within and between adjacent
      regions. We obtain a complete coverage of the human genome (neglecting the
      remaining gaps) by approximately 3200 isochores, which may be visualized as the
      ultimate chromosomal bands. Isochores visibly belong to five families
      characterized by different GC levels, as expected from previous investigations.
      Since we previously showed that isochores are tightly linked to basic biological
      properties such as gene density, replication timing, and recombination, the new
      level of detail provided by the isochore map will help the understanding of
      genome structure, function, and evolution.

PMID- 16597585
TI  - Alu-mediated 100-kb deletion in the primate genome: the loss of the agouti
      signaling protein gene in the lesser apes.
AB  - Agouti signaling protein (ASIP) is an endogenous antagonist of melanocortin
      receptors that controls a wide range of physiological functions. Its central role
      in regulation of the melanocortin system implied that ASIP has been relevant to
      the evolution of various physiological traits in primates. In this study, we have
      tried to determine DNA sequences of the ASIP gene (ASIP) of various simian
      species to find molecular evolutionary aspects of ASIP. Unexpectedly, we found
      that the whole coding region of ASIP was missing only from the gibbon genome;
      gibbons constitute a large group of hominoid species in Southeast Asia. Our
      analyses revealed that unequal homologous recombination mediated by two AluSx
      elements erased a approximately 100-kb region including ASIP from the gibbon
      genome. The data provide new evidence for the significant roles of Alu elements
      in the dynamic evolution of the primate genome.

PMID- 16597588
TI  - Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine
      kidney cells depends on the CUB domains and their association with lipid rafts.
AB  - ADAMTS13 biosynthesis appeared to occur mainly in hepatic stellate cells, but
      detection of ADAMTS13 mRNA in many other tissues suggests that vascular
      endothelium may also produce ADAMTS13. We showed that ADAMTS13 mRNA and protein
      were detectable in human umbilical vein endothelial cells, aortic endothelial
      cells, and endothelium-derived cell line (ECV304). ADAMTS13 in cell lysate or
      serum-free conditioned medium cleaved von Willebrand factor (VWF) specifically.
      ADAMTS13 and VWF were localized to the distinct compartments of endothelial
      cells. Moreover, ADAMTS13 was preferentially sorted into apical domain of ECV304
      and Madin-Darby canine kidney (MDCK) cells. Apical sorting of ADAMTS13 depended
      on the CUB domains and their association with lipid rafts. A mutation in the
      second CUB domain of ADAMTS13 (4143-4144insA), naturally occurring in patients
      with inherited thrombotic thrombocytopenic purpura, resulted in a significant
      reduction of ADAMTS13 secretion and a reversal of its polarity in MDCK cells.
      These data demonstrated that ADAMTS13 is synthesized and secreted from
      endothelial cells; the apically secreted ADAMTS13 from endothelial cells may
      contribute significantly to plasma ADAMTS13 proteases. The data also suggest a
      critical role of the CUB domains and a novel cargo-selective mechanism for apical
      sorting of a soluble ADAMTS protease in polarized cells.

PMID- 16597591
TI  - OCT-1-mediated influx is a key determinant of the intracellular uptake of
      imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low
      in vitro sensitivity to imatinib.
AB  - Intrinsic sensitivity of newly diagnosed chronic myeloid leukemia (CML) patients
      to imatinib (IC50(imatinib)) correlates with molecular response. IC50(imatinib)
      is defined as the in vitro concentration of drug required to reduce
      phosphorylation of the adaptor protein Crkl by 50%. We now show that interpatient
      variability in IC50(imatinib) is mainly due to differences in the efficiency of
      imatinib intracellular uptake and retention (IUR). In 25 untreated CML patients,
      the IC50(imatinib) strongly correlated (R (2) = -0.484, P = .014 at 2 muM
      imatinib) with the IUR of [(14)C]imatinib. The addition of prazosin, a potent
      inhibitor of OCT-1 cellular transporter, reduced the IUR and eliminated
      interpatient variability. IC50 values for the more potent BCR-ABL inhibitor
      nilotinib (AMN107) did not correlate with IC50(imatinib) (R(2) =-0.0561, P >
      .05). There was also no correlation between IC50(nilotinib) and the IUR for
      [(14)C]nilotinib (R (2) = 0.457, P > .05). Prazosin had no effect on nilotinib
      IUR, suggesting that influx of nilotinib is not mediated by OCT-1. In conclusion,
      whereas OCT-1-mediated influx may be a key determinant of molecular response to
      imatinib, it is unlikely to impact on cellular uptake and patient response to
      nilotinib. Determining interpatient and interdrug differences in cellular uptake
      and retention could allow individual optimization of kinase inhibitor therapy.

PMID- 16597592
TI  - Retrospective comparison of reduced-intensity conditioning and conventional high
      dose conditioning for allogeneic hematopoietic stem cell transplantation using
      HLA-identical sibling donors in myelodysplastic syndromes.
AB  - In this multicenter retrospective study, the outcomes of 836 patients with
      myelodysplastic syndrome (MDS) who underwent transplantation with a human
      leukocyte antigen (HLA)-identical sibling donor were analyzed according to 2
      types of conditioning: reduced-intensity conditioning (RIC) in 215 patients, and
      standard myeloablative (or high-dose) conditioning (SMC) in 621 patients. In
      multivariate analysis, the 3-year relapse rate was significantly increased after
      RIC (hazard ratio [HR], 1.64; 95% confidence interval [95% CI], 1.2-2.2; P =
      .001), but the 3-year nonrelapse mortality (NRM) rate was decreased in the RIC
      group (HR, 0.61; 95% CI, 0.41-0.91; P = .015). The 3-year probabilities of
      progression-free and overall survivals were similar in both groups (39% after SMC
      vs 33% in RIC; multivariate P = .9; and 45% vs 41%, respectively; P = .8). In
      conclusion, the lower 3-year NRM after RIC is encouraging, since these patients
      were older (age > 50 years in 73% RIC vs 28% in SMC, P < .001) and had more
      adverse pretransplantation variables. However, based on the higher risk of
      relapse, patients with no contraindications for SMC should not receive RIC
      outside of prospective randomized trials, which are needed to establish the
      position of RIC-based transplantation in the treatment of patients with MDS.

PMID- 16597594
TI  - Proper levels of c-Myb are discretely defined at distinct steps of hematopoietic
      cell development.
AB  - The definitive hematopoietic cell lineages have been proposed to originate from
      hemogenic endothelial cells during mouse embryogenesis. c-Myb is a transcription
      factor that is essential for the development of definitive hematopoiesis. To
      investigate the functional role of c-Myb in hematopoietic cell development from
      endothelial cells, we introduced a c-myb transgene expressed under the control of
      a tetracycline-regulated promoter into the c-myb(-/-) embryonic stem (ES) cell
      line, with the aim of inducing c-Myb expression at any stage and at any level.
      Induction of c-Myb expression after replating c-myb(-)(/)(-) endothelial cells
      rescued the generation and proliferation of definitive hematopoietic progenitor
      cells, suggesting that c-Myb expression in developing endothelial cells is not a
      prerequisite for their hematogenic potential. Overexpression of c-Myb, however,
      prevented the terminal differentiation of erythrocytes and megakaryocytes and
      completely abolished B-lymphocyte development. Our results indicate that c-Myb is
      a major factor that controls differentiation as well as proliferation of
      hematopoietic progenitor cells derived from hemogenic endothelial cells, and that
      appropriate levels of c-Myb protein are strictly defined at distinct
      differentiation steps of each hematopoietic cell lineage.

PMID- 16597593
TI  - A monoclonal antibody against CD148, a receptor-like tyrosine phosphatase,
      inhibits endothelial-cell growth and angiogenesis.
AB  - Angiogenesis contributes to a wide range of neoplastic, ischemic, and
      inflammatory disorders. Definition of the intrinsic molecular controls in
      angiogenic vessel growth promises novel therapeutic approaches for angiogenesis
      related diseases. CD148 (also named DEP-1/PTP eta) is a receptor-like protein
      tyrosine phosphatase that is abundantly expressed in vascular endothelial cells.
      To explore a role of CD148 in endothelial vessel formation, we generated a
      monoclonal antibody, Ab1, against the ectodomain sequence of CD148 and examined
      its effects on endothelial-cell growth and vessel formation. Here we report that
      a bivalent, but not a monovalent, form of the Ab1 antibody inhibits endothelial
      cell growth and blocks angiogenesis in mouse cornea in vivo. We further
      demonstrate that (1) bivalent Ab1 arrests cell-cycle progression of CD148
      transfected CHO cells at G(0)/G(1) phase, (2) coexpression of catalytically
      inactive CD148 mutants attenuates the Ab1-cell growth inhibition, and (3)
      bivalent Ab1 suppresses phosphorylation of ERK1/2 kinases and Met tyrosine kinase
      as activated CD148 does, with an increase in CD148-associated tyrosine
      phosphatase activity. Taken together, these findings demonstrate that Ab1-induced
      ectodomain oligomerization arrests endothelial-cell growth through catalytic
      activity of the CD148 cytoplasmic domain. The present study defines CD148 as a
      valuable molecular target for antiangiogenesis therapy.

PMID- 16597595
TI  - Rapamycin inhibits growth and survival of D816V-mutated c-kit mast cells.
AB  - Two classes of oncogenic mutations of the c-kit tyrosine kinase have been
      described: the juxtamembrane domain V560G mutation, which is preferentially found
      in gastrointestinal stromal tumors (GISTs), and the kinase domain D816V mutation,
      which is highly representative of systemic mastocytosis (SM). Here we show that
      both mutations constitutively activate the mammalian target of rapamycin (mTOR)
      signaling pathway. Surprisingly, the mTOR inhibitor rapamycin induces only
      apoptosis in HMC-1 cells bearing the D816V but not the V560G mutation. In support
      of this unexpected selectivity, rapamycin inhibits the phosphorylation of 4E-BP1,
      a downstream substrate of the mTOR pathway, but only in D816V HMC-1 cells.
      Importantly, D816V mast cells isolated from SM patients or from transgenic mice
      are sensitive to rapamycin whereas normal human or mouse mast cells are not.
      Thus, rapamycin inhibition appears specific to the D816V mutation. At present
      there is no effective cure for SM patients with the D816V mutation. The data
      presented here provide a rationale to test whether rapamycin could be a possible
      treatment for SM and other hematologic malignancies with the D816V mutation.

PMID- 16597597
TI  - The Ki67 proliferation index is a quantitative indicator of clinical risk in
      mantle cell lymphoma.

PMID- 16597598
TI  - Increased soluble urokinase plasminogen activator receptor (suPAR) serum levels
      after granulocyte colony-stimulating factor treatment do not predict successful
      progenitor cell mobilization in vivo.

PMID- 16597596
TI  - Gene expression profiling of adult acute myeloid leukemia identifies novel
      biologic clusters for risk classification and outcome prediction.
AB  - To determine whether gene expression profiling could improve risk classification
      and outcome prediction in older acute myeloid leukemia (AML) patients, expression
      profiles were obtained in pretreatment leukemic samples from 170 patients whose
      median age was 65 years. Unsupervised clustering methods were used to classify
      patients into 6 cluster groups (designated A to F) that varied significantly in
      rates of resistant disease (RD; P < .001), complete response (CR; P = .023), and
      disease-free survival (DFS; P = .023). Cluster A (n = 24), dominated by NPM1
      mutations (78%), normal karyotypes (75%), and genes associated with signaling and
      apoptosis, had the best DFS (27%) and overall survival (OS; 25% at 5 years).
      Patients in clusters B (n = 22) and C (n = 31) had the worst OS (5% and 6%,
      respectively); cluster B was distinguished by the highest rate of RD (77%) and
      multidrug resistant gene expression (ABCG2, MDR1). Cluster D was characterized by
      a "proliferative" gene signature with the highest proportion of detectable
      cytogenetic abnormalities (76%; including 83% of all favorable and 34% of
      unfavorable karyotypes). Cluster F (n = 33) was dominated by monocytic leukemias
      (97% of cases), also showing increased NPM1 mutations (61%). These gene
      expression signatures provide insights into novel groups of AML not predicted by
      traditional studies that impact prognosis and potential therapy.

PMID- 16597600
TI  - Improved outcome in central nervous system aspergillosis.

PMID- 16597599
TI  - Treatment of chronic hepatitis C in patients with glucose-6-phosphate
      dehydrogenase deficiency: is ribavirin harmful?

PMID- 16597601
TI  - The management of meningeal lymphoma in patients with HIV in the era of HAART:
      intrathecal depot cytarabine is effective and safe.

PMID- 16597602
TI  - Pathology of "Berkeley" sickle-cell mice includes gallstones and priapism.

PMID- 16597603
TI  - Remarkable activity of novel agents bortezomib and thalidomide in patients not
      responding to donor lymphocyte infusions following nonmyeloablative allogeneic
      stem cell transplantation in multiple myeloma.

PMID- 16597604
TI  - Effects of expression of p53 and Gadd45 on osmotic tolerance of renal inner
      medullary cells.
AB  - The response of renal inner medullary (IM) collecting duct cells (mIMCD3) to high
      NaCl involves increased expression of Gadd45 and p53, both of which have
      important effects on growth and survival of the cells. However, mIMCD3 cells,
      being immortalized by SV40, proliferate rapidly, which is known to sensitize
      cells to high NaCl, whereas IM cells in situ proliferate very slowly and survive
      much higher levels of NaCl. In the present studies, we have examined the
      importance of Gadd45 and p53 for survival of normal IM cells in their usual high
      NaCl environment by using more slowly proliferating second-passage mouse inner
      medullary epithelial (p2mIME) cells and comparing cells from wild-type and gene
      knockout mice. Acutely elevating NaCl (and/or urea) reduces Gadd45a, but
      increases Gadd45b and Gadd45g mRNA, depending on the mix of NaCl and urea and the
      rate of increase of osmolality. Nevertheless, p2mIME cells from Gadd45b(-/-),
      Gadd45g(-/-), and Gadd45bg(-/-) mice survive elevation of NaCl (or urea)
      essentially the same as do wild-type cells. p53(-/-) Cells do not tolerate as
      high a concentration of NaCl (or urea) as p53(+/+) cells, but urinary
      concentrating ability of p53(-/-) mice is normal, as is the histology of inner
      medullas from p53(-/-) and Gadd45abg(-/-) mice. Thus although Gadd45 and p53 may
      play roles in osmotically stressed mIMCD3 cells, we do not find that their
      expression makes an important difference, either for Gadd45 in slower
      proliferating p2mIME cells or for Gadd45 or p53 in normal inner medullary
      epithelial cells in situ.

PMID- 16597605
TI  - Aldosterone infusion with high-NaCl diet increases blood pressure in obese but
      not lean Zucker rats.
AB  - Insulin-resistant, obese Zucker rats have blunted pressure natriuresis and are
      mildly hypertensive. This may involve inappropriate regulation of the renin
      angiotensin-aldosterone system. To evaluate mechanisms underlying this defect, we
      employed the model of aldosterone escape. Male lean (L) and obese (O) Zucker rats
      were infused with aldosterone (2.8 mug/g body wt(3/4)) via osmotic minipump while
      being fed a 0.02% NaCl diet (LS). After 4 days, six rats of each type were
      switched to a high-NaCl (HS) diet (4%) for 4 additional days. Mean arterial blood
      pressure measured by radiotelemetry was significantly increased by the HS diet
      only in obese rats (final mean mmHg): 104 (LLS), 99 (LHS), 103 (OLS), and 115
      (OHS). Obese rats had relatively increased renal cortical abundance of the
      bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and whole kidney alpha- and
      beta-ENaC (epithelial sodium channel) relative to lean rats. However, band
      density for the thiazide-sensitive (Na-Cl) cotransporter (NCC) was similarly
      reduced by HS in lean and obese rats ( approximately 50%). Obese rats had
      relatively reduced creatinine clearances and plasma renin activities, effects
      exacerbated by HS. Furthermore, HS resulted in a 129% increase in urinary
      nitrates plus nitrites excretion in lean rats and led to, in contrast, a 46%
      reduction in obese rats. Plasma sodium and potassium concentrations were
      increased by HS in obese but not lean rats. Thus we demonstrate an impaired
      response to aldosterone infusion in obese relative to lean Zucker rats. This
      impairment may involve increased sodium reabsorption via NKCC2 or ENaC, decreased
      glomerular filtration rate, and/or nitric oxide bioavailability.

PMID- 16597606
TI  - Role of renal cortical cyclooxygenase-2 expression in hyperfiltration in rats
      with high-protein intake.
AB  - Renal cortical cyclooxygenase-2 (COX-2) is restricted to the macula densa and
      adjacent cortical thick ascending limbs (MD/cTALH). Renal cortical COX-2
      increases in response to diabetes and renal ablation, both of which are
      characterized by hyperfiltration and reduced NaCl delivery to the MD due to
      increased proximal NaCl reabsorption. High-protein intake also induces
      hyperfiltration and decreases NaCl delivery to the MD due to increased NaCl
      reabsorption proximally. We investigated whether high protein induces cortical
      COX-2 and whether cortical COX-2 contributes to high protein-induced
      hyperfiltration and increased intrarenal renin biosynthesis. Cortical COX-2
      increased after protein loading but decreased after protein restriction. COX-2
      inhibition attenuated high protein-induced hyperfiltration but had no effect on
      high protein-induced intrarenal renin elevation. Therefore, induction of cortical
      COX-2 contributed to high protein-induced hyperfiltration but not intrarenal
      renin elevation. In the kidney cortex, neuronal nitric oxide synthase (nNOS) is
      also localized to the MD, and interactions between intrarenal nNOS and COX-2
      systems have been proposed. Cortical COX-2 elevation seen in salt restriction was
      blocked by nNOS inhibiton. Cortical nNOS expression also increased after protein
      loading, and inhibition of nNOS activity completely reversed high protein-induced
      cortical COX-2 elevation and hyperfiltration. These results indicate that NO is a
      mediator of high protein-induced cortical COX-2 elevation and suggest that both
      intrarenal nNOS and COX-2 systems appear to regulate afferent arteriolar tone and
      subsequent hyperfiltration seen in high-protein intake.

PMID- 16597607
TI  - Microbial nucleic acids pay a Toll in kidney disease.
AB  - Nucleic acids provide more than the genetic code that determines the
      morphological and functional phenotype of microbes and eukaryotes. In fact,
      nucleic acids have immunomodulatory functions as they are recognized by a set of
      pattern-recognition receptors that initiate and modulate immune responses in the
      host. Toll-like receptor (TLR)-3 recognizes double-stranded RNA, TLR7 and TLR8
      recognize single-stranded RNA, CpG-DNA is a ligand for TLR9, and all of these
      TLRs are expressed in the nephritic kidney. In this review, we summarize recent
      advances in this field and discuss new hypotheses for the pathogenesis of kidney
      diseases that are triggered by infectious organisms.

PMID- 16597608
TI  - Autocrine VEGF-A system in podocytes regulates podocin and its interaction with
      CD2AP.
AB  - Vascular endothelial growth factor (VEGF-A) signaling is required for endothelial
      cell differentiation, vasculogenesis, angiogenesis, and vascular patterning.
      During kidney morphogenesis, podocyte VEGF-A guides endothelial cells toward
      developing glomeruli. Podocyte VEGF-A expression continues throughout life but
      its function after completion of development remains unclear. Here, we examined
      the expression of VEGF-A and its receptors VEGFR1, VEGFR2, NP1, and NP2 in
      conditionally immortalized mouse podocytes cultured in undifferentiated and
      differentiated conditions using RT-PCR and Western analysis. VEGF-A secretion was
      assessed by ELISA and Western analysis. Upon podocyte differentiation, VEGF-A
      protein expression and secretion increased threefold. Differentiated podocytes
      expressed eightfold higher VEGFR2 mRNA levels than undifferentiated podocytes,
      whereas VEGFR1, sVEGFR1, NP1, and NP2 mRNA levels were similar. We examined the
      regulation and function of the VEGF-A system by exposing differentiated podocytes
      to recombinant VEGF(165) (20 ng/ml) or control media for 24 h. VEGF(165) induced
      a twofold increase in VEGFR2 mRNA and protein levels, whereas VEGFR1, sVEGFR1,
      NP1, and NP2 mRNA levels remained unchanged. VEGF(165) induced VEGFR2
      phosphorylation. VEGF(165) reduced podocyte apoptosis approximately 40%, whereas
      anti-VEGFR2 neutralizing antibody enhanced it twofold. We determined that VEGF-A
      signaling regulates slit diaphragm proteins by inducing a dose-response podocin
      upregulation and increasing its interaction with CD2AP. The data indicate that
      podocytes in culture have a functional autocrine VEGF-A system that is regulated
      by differentiation and ligand availability. VEGF-A functions in podocytes include
      promoting survival through VEGFR2, inducing podocin upregulation and increasing
      podocin/CD2AP interaction.

PMID- 16597609
TI  - Effect of sodium delivery on superoxide and nitric oxide in the medullary thick
      ascending limb.
AB  - Hypertension is associated with increased levels of oxidative stress and
      medullary renal injury. Previous studies have shown that elevations in renal
      perfusion pressure increase Na(+) delivery to the medullary thick ascending limb
      (mTAL), and enhancement of NaCl transport in the outer medulla has been reported
      in many experimental forms of hypertension. This study examined the effects of
      increased Na(+) and fluid delivery in mTAL perfused in vitro on the generation of
      superoxide. Osmolality was maintained constant between low- and high-Na(+)
      perfusates by adjusting with choline Cl(-). Real-time fluorescent microscopic
      techniques were used to determine the generation of superoxide and nitric oxide
      in individual mTAL cells using dihydroethidium and DAF-FM dyes, respectively.
      Increasing the Na(+) concentration of the perfusate from 60 to 149 mM or luminal
      flow rate from 5 to 20 nl/min (with fixed Na(+) concentration of 60 mM)
      significantly increased superoxide generation and decreased nitric oxide in mTAL.
      These effects were inhibited when active transport of Na(+) was inhibited by
      ouabain. We conclude that increases in luminal Na(+) concentration and/or flow
      rate can increase the generation of superoxide in mTAL and reduce nitric oxide
      bioavailability. This may lead to reduction in medullary blood flow and promote
      hypoxia and tubular necrosis within the renal medulla during in hypertension.

PMID- 16597610
TI  - Novel cystogenic role of basic fibroblast growth factor in developing rodent
      kidneys.
AB  - Basic fibroblast growth factor (bFGF) is a heparin-binding growth factor that is
      accumulated in human dysplastic and cystic renal diseases. Previous studies have
      shown that bFGF can modulate the growth of developing renal tubules; however, its
      role in the pathogenesis of renal cyst formation is not clearly understood. Here,
      we tested the hypothesis that overexpression of bFGF in developing rodent kidneys
      induces cyst formation in vivo. We used two different adenoviral-mediated gene
      transferring approaches to overexpress bFGF in developing rodent kidneys.
      Initially, metanephric kidney (MK) explants harvested from embryonic day 15
      Sprague-Dawley rats were infected with adenoviral vectors (rAd) encoding human
      bFGF or LacZ genes and transplanted under the renal capsule of adult female rats.
      Subsequently, to determine whether bFGF could induce renal cysts in developing
      kidneys with an intact renal collecting system, we injected rAd-bFGF or LacZ
      vectors in the retroorbital plexus of newborn mice. Basic FGF induced a more
      efficient integration of the MK explants into the host kidneys and increased the
      vascularization and proliferation of developing tubules, leading to tubular
      dilatation and rapid formation of renal cysts. In addition, we successfully
      expressed human bFGF in the kidney of newborn mice in vivo and induced tubular
      dilatation and renal cysts. In contrast, mice injected with rAd-lacZ did not
      develop tubular dilatation or renal cysts. To the best of our knowledge, these
      experiments show for the first time that overexpression of bFGF in developing
      rodent kidneys can induce the formation of renal cysts in vivo.

PMID- 16597611
TI  - Kinetics of urothelial ATP release.
AB  - Recent reports have proposed that the urothelium can sense mechanical stretch and
      communicate this information to sensory afferent neurons by the release of ATP
      into the vicinity of P2X-containing neurons. This report investigates the
      bidirectional release of ATP by in vitro rabbit urothelium. ATP was measured
      using the luciferin-luciferase assay. Immediately after washing of both sides of
      the epithelium, there was a linear increase in ATP content in the mucosal
      compartment with a rate of 23 +/- 6.5 fmol x min(-1) x cm(-2) (n = 18). Serosal
      ATP content increased as a saturating exponential function, suggesting a constant
      rate of release and degradation of ATP by ectonucleotidases/exonucleotidases. The
      presence of a serosal ectonucleotidase/exonucleotidases was demonstrated by the
      time-dependent decrease in exogenously added ATP. The maximum rate of hydrolysis
      was 11 pmol x min(-1) x cm(-2) with a K(m) of 0.49 microM. The time course of
      serosal ATP release was modeled as a constant rate of release (d: mol x min(-1) x
      cm(-2)) and rate constant of hydrolysis (k(h): min(-)). In control conditions d
      was 18 fmol x min(-1) x cm(-2) and k(h) of 0.056 +/- 0.01 min(-) (n = 18). Steady
      state serosal chamber content is 370 +/- 90 fmol/cm(2), and concentration is 50
      +/- 1.2 x 10(-12) M. Stretching the tissue resulted in a transient fivefold
      increase in the rate of mucosal ATP release and a transient sixfold increase in
      serosal ATP release. Half-osmotic strength solutions increased mucosal release by
      10-fold and serosal release by 5-fold. Tissue damage resulted in a step-increase
      in mucosal chamber ATP content by 6.6 +/- 1 pmol/cm(2) and serosal chamber ATP by
      0.1 +/- 0.06 pmol/cm(2) (n = 5).

PMID- 16597612
TI  - Ouabain modulation of endothelial calcium signaling in descending vasa recta.
AB  - Using fura 2-loaded vessels, we tested whether ouabain modulates endothelial
      cytoplasmic calcium concentration ([Ca(2+)](CYT)) in rat descending vasa recta
      (DVR). Over a broad range between 10(-10) and 10(-4) M, ouabain elicited biphasic
      peak and plateau [Ca(2+)](CYT) elevations. Blockade of voltage-gated Ca(2+) entry
      with nifedipine did not affect the response to ouabain mitigating against a role
      for myo-endothelial gap junctions. Reduction of extracellular Na(+) concentration
      ([Na(+)](o)) or Na(+)/Ca(2+) exchanger (NCX) inhibition with SEA-0400 (10(-6) M)
      elevated [Ca(2+)](CYT), supporting a role for NCX in the setting of basal
      [Ca(2+)](CYT). SEA-0400 abolished the [Ca(2+)](CYT) response to ouabain
      implicating NCX as a mediator. The transient peak phase of [Ca(2+)](CYT)
      elevation that followed either ouabain or reduction of [Na(+)](o) was abolished
      by 2-aminoethoxydiphenyl borate (5 x 10(-5) M). Cation channel blockade with
      La(3+) (10 muM) or SKF-96365 (10 muM) also attenuated the ouabain-induced
      [Ca(2+)](CYT) response. Ouabain pretreatment increased the [Ca(2+)](CYT)
      elevation elicited by bradykinin (10(-7) M). We conclude that inhibition of
      ouabain-sensitive Na(+)-K(+)-ATPase enhances DVR endothelial Ca(2+) store loading
      and modulates [Ca(2+)](CYT) signaling through mechanisms that involve NCX, Ca(2+)
      release, and cation channel activation.

PMID- 16597613
TI  - Caspase-dependent and -independent pathways for cadmium-induced apoptosis in
      cultured kidney proximal tubule cells.
AB  - The nephrotoxic metal cadmium at micromolar concentrations induces apoptosis of
      rat kidney proximal tubule (PT) cells within 3-6 h of exposure. The underlying
      cell death pathways remain poorly defined. Using Hoechst 33342/ethidium bromide
      nuclear staining and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium
      bromide (MTT) cell death assays, 10-50 microM cadmium induced apoptosis of
      immortalized rat kidney cells derived from the S1-segment of PT at 6 and 24 h,
      but necrosis at 24 h only. Cadmium (10-50 microM) also caused mitochondrial
      cytochrome c (cyt. c)- and apoptosis-inducing factor release at 24 h, but not at
      6 h, as measured by immunofluorescence imaging and immunoblotting. Caspases-9 and
      -3 were activated only by 10 microM cadmium for 24 h, and accordingly apoptosis
      was significantly reduced by the respective inhibitors (z-LEHD-fmk, z-DEVD-fmk;
      10 microg/ml) at 24 h, but not at 6 h, without affecting necrosis. At 6 h, 10
      microM cadmium increased the activity of the calcium-activated protease calpain,
      but not at 24 h, and calpain inhibitors (ALLN, PD 150606; 10-30 microM) blocked
      apoptosis by 10 microM cadmium at 3-6 h. However, PD-150606 also attenuated
      caspase-3 activity and apoptosis at 24 h, suggesting calpain-dependent caspase
      activation. Thus cadmium-induced apoptosis of PT cells involves a complex and
      sensitive interplay of signaling cascades involving mitochondrial proapoptotic
      factors, calpains and caspases, whose activation is also determined by cadmium
      concentration and the duration of cadmium exposure.

PMID- 16597614
TI  - FGF-10 and its receptor exhibit bidirectional paracrine targeting to urothelial
      and smooth muscle cells in the lower urinary tract.
AB  - Control of the regenerative properties of urothelial tissue would greatly aid the
      clinician in the management of urinary tract disease and disorders. Fibroblast
      growth factor 10 (FGF-10) is a mitogen which is particularly promising as a
      protein therapy for urothelial injury. The spatial synthesis, transport,
      targeting, and mechanistic pathway of FGF-10 and its receptor were studied in a
      human urothelial cell culture model and in fixed sections of lower urinary tract
      tissue. Synthesis of FGF-10 was restricted to mesenchymal fibroblasts, and
      secreted FGF-10 exhibited paracrine transport to two proximal sites, transitional
      epithelium and smooth muscle cell bundles, both of which were also the exclusive
      sites of FGF-10 receptor synthesis. The addition of recombinant FGF-10 to
      quiescent urothelial cells in vitro was sufficient to stimulate DNA synthesis.
      This stimulation was through a pathway independent of the epidermal growth factor
      receptor pathway. Deconvolution, light and transmission electron microscopic
      studies captured FGF-10 and its receptor in association with the urothelial cell
      surface, in cytoplasm, and within nuclei, observations that describe the
      mechanism that transduces the mitogenic signal in these tissues. Localization of
      the FGF-10 receptor to the superficial urothelial layer is clinically significant
      because intravesical administration of FGF-10 may provide the clinician a means
      to control the turnover of transitional epithelium in bladder disorders such as
      interstitial cystitis.

PMID- 16597615
TI  - Physiological oxygenation status is required for fully differentiated phenotype
      in kidney cortex proximal tubules.
AB  - Hypoxia has been suspected to trigger transdifferentiation of renal tubular cells
      into myofibroblasts in an epithelial-to-mesenchymal transition (EMT) process. To
      determine the functional networks potentially altered by hypoxia, rat renal
      tubule suspensions were incubated under three conditions of oxygenation ranging
      from normoxia (lactate uptake) to severe hypoxia (lactate production).
      Transcriptome changes after 4 h were analyzed on a high scale by restriction
      fragment differential display. Among 1,533 transcripts found, 42% were maximally
      expressed under severe hypoxia and 8% under mild hypoxia (Po(2) = 48 mmHg),
      suggesting two different levels of oxygen sensing. Normoxia was required for full
      expression of the proximal tubule-specific transcripts 25-hydroxyvitamin D 1
      hydroxylase (Cyp27b1) and l-pyruvate kinase (Pklr), transcripts involved in
      tissue cohesion such as fibronectin (Fn1) and N-cadherin (Cdh2), and non-muscle
      type myosin transcripts. Mild hypoxia increased myogenin transcript level.
      Conversely, severe hypoxia increased transcripts involved in extracellular matrix
      remodeling, those of muscle-type myosins, and others involved in creatine
      phosphate synthesis and lactate transport (Slc16a7). Accordingly, microscopy
      showed loss of tubule aggregation under hypoxia, without tubular disruption.
      Hypoxia also increased the levels of kidney-specific transcripts normally
      restricted to the less oxygenated medullary zone and others specific for the
      distal part of the nephron. We conclude that extensive oxygen supply to the
      kidney tubule favors expression of its differentiated functions specifically in
      the proximal tubule, whose embryonic origin is mesenchymal. The phenotype changes
      could potentially permit transient adaptation to hypoxia but also favor
      pathological processes such as tissue invasion.

PMID- 16597616
TI  - Ubiquitous calpains promote caspase-12 and JNK activation during endoplasmic
      reticulum stress-induced apoptosis.
AB  - Ubiquitously expressed mu- and m-calpain proteases are implicated in development
      and apoptosis. They consist of 80-kDa catalytic subunits encoded by the capn1 and
      capn2 genes, respectively, and a common 28-kDa regulatory subunit encoded by the
      capn4 gene. The regulatory subunit is required to maintain the stability and
      activity of mu- and m-calpains. Accordingly, genetic disruption of capn4 in the
      mouse eliminated both ubiquitous calpain activities. In embryonic fibroblasts
      derived from these mice, calpain deficiency correlated with resistance to
      endoplasmic reticulum (ER) stress-induced apoptosis, and this was directly
      related to a calpain requirement for activation of both caspase-12 and the ASK1
      JNK cascade. This study provides compelling genetic evidence for calpain's role
      in caspase-12 activation at the ER, and reveals a novel role for the ubiquitous
      calpains in ER-stress induced apoptosis and JNK activation.

PMID- 16597618
TI  - Streptococcus pneumoniae recruits complement factor H through the amino terminus
      of CbpA.
AB  - Streptococcus pneumoniae, a human pathogen, is naturally capable of colonizing
      the upper airway and sometimes disseminating to remote tissue sites. Previous
      studies have shown that S. pneumoniae is able to evade complement-mediated innate
      immunity by recruiting complement factor H (FH), a complement alternative pathway
      inhibitor. Pneumococcal binding to FH has been attributed to choline-binding
      protein A (CbpA) of S. pneumoniae and its allelic variants, all of which are
      surface-exposed proteins. In this study, we sought to determine the molecular
      basis of the CbpA-FH binding interaction. Initial deletional analysis of the CbpA
      protein in strain D39 (capsular serotype 2) revealed that the N-terminal region
      of 89 amino acids in the mature CbpA protein is required for FH binding.
      Immunofluorescence microscopy analysis showed that this region of CbpA is also
      necessary for FH deposition to the surface of the intact pneumococci. Moreover,
      recombinant proteins representing the 104 amino acids of the N-terminal CbpA
      alone was sufficient for high affinity binding to FH (KD < 1 nm). The FH binding
      activity was finally localized to a 12-amino acid motif in the N-terminal CbpA by
      peptide mapping. Further kinetic analysis suggested that additional amino acids
      downstream of the 12-amino acid motif provide necessary structural or
      conformational support for the CbpA-FH interaction. The 12-amino acid motif and
      its adjacent regions contain highly conserved residues among various CbpA
      alleles, suggesting that this region may mediate FH binding in multiple
      pneumococcal strains.

PMID- 16597619
TI  - Rhodobacter capsulatus XdhC is involved in molybdenum cofactor binding and
      insertion into xanthine dehydrogenase.
AB  - Rhodobacter capsulatus xanthine dehydrogenase (XDH) is a cytoplasmic enzyme with
      an (alphabeta)2 heterodimeric structure that is highly identical to homodimeric
      eukaryotic xanthine oxidoreductases. The crystal structure revealed that the
      molybdenum cofactor (Moco) is deeply buried within the protein. A protein
      involved in Moco insertion and XDH maturation has been identified, which was
      designated XdhC. XdhC was shown to be essential for the production of active XDH
      but is not a subunit of the purified enzyme. Here we describe the purification of
      XdhC and the detailed characterization of its role for XDH maturation. We could
      show that XdhC binds Moco in stoichiometric amounts, which subsequently can be
      inserted into Moco-free apo-XDH. A specific interaction between XdhC and XdhB was
      identified. We show that XdhC is required for the stabilization of the sulfurated
      form of Moco present in enzymes of the xanthine oxidase family. Our findings
      imply that enzyme-specific proteins exist for the biogenesis of molybdoenzymes,
      coordinating Moco binding and insertion into their respective target proteins. So
      far, the requirement of such proteins for molybdoenzyme maturation has been
      described only for prokaryotes.

PMID- 16597617
TI  - Receptor specificity of the fibroblast growth factor family. The complete
      mammalian FGF family.
AB  - In mammals, fibroblast growth factors (FGFs) are encoded by 22 genes. FGFs bind
      and activate alternatively spliced forms of four tyrosine kinase FGF receptors
      (FGFRs 1-4). The spatial and temporal expression patterns of FGFs and FGFRs and
      the ability of specific ligand-receptor pairs to actively signal are important
      factors regulating FGF activity in a variety of biological processes. FGF
      signaling activity is regulated by the binding specificity of ligands and
      receptors and is modulated by extrinsic cofactors such as heparan sulfate
      proteoglycans. In previous studies, we have engineered BaF3 cell lines to express
      the seven principal FGFRs and used these cell lines to determine the receptor
      binding specificity of FGFs 1-9 by using relative mitogenic activity as the
      readout. Here we have extended these semiquantitative studies to assess the
      receptor binding specificity of the remaining FGFs 10-23. This study completes
      the mitogenesis-based comparison of receptor specificity of the entire FGF family
      under standard conditions and should help in interpreting and predicting in vivo
      biological activity.

PMID- 16597620
TI  - Antagonistic regulation of Escherichia coli ribosomal RNA rrnB P1 promoter
      activity by GreA and DksA.
AB  - The Escherichia coli proteins DksA, GreA, and GreB are all structural homologs
      that bind the secondary channel of RNA polymerase (RNAP) but are thought to act
      at different levels of transcription. DksA, with its co-factor ppGpp, inhibits
      rrnB P1 transcription initiation, whereas GreA and GreB activate RNAP to cleave
      back-tracked RNA during elongational pausing. Here, in vivo and in vitro evidence
      reveals antagonistic regulation of rrnB P1 transcription initiation by Gre
      factors (particularly GreA) and DksA; GreA activates and DksA inhibits. DksA
      inhibition is epistatic to GreA activation. Both modes of regulation are ppGpp
      independent in vivo but DksA inhibition requires ppGpp in vitro. Kinetic
      experiments and studies of rrnB P1-RNA polymerase complexes suggest that GreA
      mediates conformational changes at an initiation step in the absence of NTP
      substrates, even before DksA acts. GreA effects on rrnB P1 open complex
      conformation reveal a new feature of GreA distinct from its general function in
      elongation. Our findings support the idea that a balance of the interactions
      between the three secondary channel-binding proteins and RNAP can provide a new
      mode for regulating transcription.

PMID- 16597621
TI  - Ca2+-dependent control of the permeability properties of the mitochondrial outer
      membrane and voltage-dependent anion-selective channel (VDAC).
AB  - Cell function depends on the distribution of cytosolic and mitochondrial factors
      across the outer mitochondrial membrane (OMM). Passage of metabolites through the
      OMM has been attributed to the voltage-dependent anion-selective channel (VDAC),
      which can form a large conductance and permanently open a channel in lipid
      bilayers. However, recent data indicate that the transport of metabolites through
      the OMM is controlled in the cells. Recognizing that the bilayer studies had been
      commonly conducted at supraphysiological [Ca2+] and [K+], we determined the
      effect of Ca2+ on VDAC activity. In liposomes, the purified VDAC displays Ca2+
      dependent control of the molecular cut-off size and shows Ca2+-regulated Ca2+
      permeability in the physiological [Ca2+] range. In bilayer experiments, at
      submicromolar [Ca2+], the purified VDAC or isolated OMM does not show sustained
      large conductance but rather exhibits gating between a nonconducting state and
      various subconductance states. Ca2+ addition causes a reversible increase in the
      conductance and may evoke channel opening to full conductance. Furthermore,
      single cell imaging data indicate that Ca2+ may facilitate the cation and ATP
      transport across the OMM. Thus, the VDAC gating is dependent on the physiological
      concentrations of cations, allowing the OMM to control the passage of ions and
      some small molecules. The OMM barrier is likely to decrease during the calcium
      signal.

PMID- 16597622
TI  - Structure of severe acute respiratory syndrome coronavirus receptor-binding
      domain complexed with neutralizing antibody.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV, or SCV), which
      caused a world-wide epidemic in 2002 and 2003, binds to a receptor, angiotensin
      converting enzyme 2 (ACE2), through the receptor-binding domain (RBD) of its
      envelope (spike, S) glycoprotein. The RBD is very immunogenic; it is a major SCV
      neutralization determinant and can elicit potent neutralizing antibodies capable
      of out-competing ACE2. However, the structural basis of RBD immunogenicity, RBD
      mediated neutralization, and the role of RBD in entry steps following its binding
      to ACE2 have not been elucidated. By mimicking immune responses with the use of
      RBD as an antigen to screen a large human antibody library derived from healthy
      volunteers, we identified a novel potent cross-reactive SCV-neutralizing
      monoclonal antibody, m396, which competes with ACE2 for binding to RBD, and
      determined the crystal structure of the RBD-antibody complex at 2.3-A resolution.
      The antibody-bound RBD structure is completely defined, revealing two previously
      unresolved segments (residues 376-381 and 503-512) and a new disulfide bond
      (between residues 378 and 511). Interestingly, the overall structure of the m396
      bound RBD is not significantly different from that of the ACE2-bound RBD. The
      antibody epitope is dominated by a 10-residue-long protruding beta6-beta7 loop
      with two putative ACE2-binding hotspot residues (Ile-489 and Tyr-491). These
      results provide a structural rationale for the function of a major determinant of
      SCV immunogenicity and neutralization, the development of SCV therapeutics based
      on the antibody paratope and epitope, and a retrovaccinology approach for the
      design of anti-SCV vaccines. The available structural information indicates that
      the SCV entry may not be mediated by ACE2-induced conformational changes in the
      RBD but may involve other conformational changes or/and yet to be identified
      coreceptors.

PMID- 16597623
TI  - Regulation of IkappaB kinase (IKK) complex by IKKgamma-dependent phosphorylation
      of the T-loop and C terminus of IKKbeta.
AB  - The mechanistic relationship of phosphorylation of the C terminus of IKKbeta with
      phosphorylation of its T-loop kinase domain within the IKK complex remained
      unclear. We investigated the regulatory role of the serine cluster residing
      immediately adjacent to the HLH domain and of the serines in the NEMO/IKKgamma
      binding domain (NBD/gammaBD) in the C-terminal portion of IKKbeta in MEFs
      deficient in IKKbeta and IKKalpha and in yeast reconstitution system. We show
      that phosphorylation events at the C terminus of IKKbeta can be divided into
      autophosphorylation of the serine cluster adjacent to the HLH domain and
      phosphorylation of the NBD/gammaBD. Autophosphorylation of the serine cluster
      occurs immediately after IKK activation and requires IKKgamma. In MEFs, this
      autophosphorylation does not have the down-regulatory function on the IKK complex
      that was previously described (1). On the other hand, phosphorylation of the
      NBD/gammaBD regulates IKKgamma-dependent phosphorylation of the T-loop activation
      domain in IKKbeta and, hence, IKK complex activation. Our study suggests that,
      within the IKK complex, modulation of the NBD/gammaBD by IKKgamma is upstream to
      the T-loop phosphorylation.

PMID- 16597624
TI  - Co-activation of atrial natriuretic factor promoter by Tip60 and serum response
      factor.
AB  - Tat-interactive protein 60 (Tip60) is a member of the MYST family of histone
      acetyltransferases (HATs). In addition to its HAT domain, Tip contains a
      heterochromatin-associated protein 1-like chromodomain and a zinc finger-like
      domain. Several alternative splice variants of Tip60 have been characterized,
      including full-length Tip60alpha, Tip60beta (which lacks exon V encoded by the
      Tip60 gene), and Tip55 (which encodes a novel 103-amino-acid C terminus). We
      report here that isoproteins recognized by a pan-Tip60 antibody are strongly and
      transiently expressed between embryonic days 8 and 11 in the embryonic mouse
      myocardium. A functional role for Tip60 isoproteins in cardiac myocyte
      differentiation is suggested by immunoprecipitation experiments showing that
      Tip60alpha, Tip60beta, and Tip55 can bind serum response factor (SRF) and by
      transient transfection assessments showing that Tip60 and SRF cooperatively
      activate the atrial natriuretic factor promoter. Although this combinatorial
      activity is inhibited by histone deacetylase 7, it was unexpectedly enhanced by
      point mutation of the HAT domain. Ablation of the chromodomain from Tip60beta
      caused derepression. These findings suggest that Tip60 modulates expression of
      SRF-dependent cardiac genes.

PMID- 16597625
TI  - Loss of a primordial identity element for a mammalian mitochondrial
      aminoacylation system.
AB  - In mammalian mitochondria the translational machinery is of dual origin with
      tRNAs encoded by a simplified and rapidly evolving mitochondrial (mt) genome and
      aminoacyl-tRNA synthetases (aaRS) coded by the nuclear genome, and imported. Mt
      tRNAs are atypical with biased sequences, size variations in loops and stems, and
      absence of residues forming classical tertiary interactions, whereas synthetases
      appear typical. This raises questions about identity elements in mt-tRNAs and
      adaptation of their cognate mt-aaRSs. We have explored here the human mt
      aspartate system in which a prokaryotic-type AspRS, highly similar to the
      Escherichia coli enzyme, recognizes a bizarre tRNA(Asp). Analysis of human mt
      tRNA(Asp) transcripts confirms the identity role of the GUC anticodon as in other
      aspartylation systems but reveals the non-involvement of position 73. This
      position is otherwise known as the site of a universally conserved major
      aspartate identity element, G73, also known as a primordial identity signal. In
      mt-tRNA(Asp), position 73 can be occupied by any of the four nucleotides without
      affecting aspartylation. Sequence alignments of various AspRSs allowed placing
      Gly-269 at a position occupied by Asp-220, the residue contacting G73 in the
      crystallographic structure of E. coli AspRS-tRNA(Asp) complex. Replacing this
      glycine by an aspartate renders human mt-AspRS more discriminative to G73.
      Restriction in the aspartylation identity set, driven by a rapid mutagenic rate
      of the mt-genome, suggests a reverse evolution of the mt-tRNA(Asp) identity
      elements in regard to its bacterial ancestor.

PMID- 16597626
TI  - Arabidopsis mutants by activation tagging in which photosynthesis genes are
      expressed in dedifferentiated calli.
AB  - In an effort to delineate the precise mechanisms underlying the organ-specific
      expression of photosynthesis genes, Arabidopsis lines homozygous for each
      transgene construct made with the gene for hygromycin B phosphotransferase or
      beta-glucuronidase (GUS) placed under control of the promoter of the nuclear gene
      for the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RBCS
      3B) were constructed. Furthermore, activation tagging with T-DNA possessing
      quadruply repeated enhancers derived from the cauliflower mosaic virus 35S
      promoter was applied to a transgenic line of Arabidopsis. Mutants resistant to
      hygromycin B during the growth of calli generated from non-green roots on callus
      inducing medium resulted from the expression of hygromycin B phosphotransferase
      driven by the RBCS-3B promoter. Three mutant lines, ces101 to ces103 (callus
      expression of RBCS), were obtained from approximately 4,000 calli resistant to a
      selectable marker for transformation. The active transcription driven by the RBCS
      3B promoter in all the calli of ces mutants was confirmed by expression of both
      the GUS reporter gene and endogenous RBCS-3B. Chlorophyll and carotenoids, as
      well as light-dependent O(2) evolution, have been detected in the calli of all
      ces mutants. The loci where T-DNA was integrated in the ces101 line were
      determined by thermal asymmetric interlaced (TAIL)-PCR. The introduction of a DNA
      fragment harboring the gene for receptor-like kinase placed under the influence
      of enhancers into the parental line reproduced the phenotype of ces mutants. We
      have thus concluded that CES101 is a receptor-like kinase. The strategy presented
      in this investigation may promise to select a greater number of ces mutants.

PMID- 16597627
TI  - Homicides involving knives and other sharp objects in Scotland, 1981-2003.
AB  - BACKGROUND: Homicide rates have been increasing in Scotland, and homicides
      involving knives are of particular concern. METHODS: and results We use mortality
      and population data from 1981 to 2003 to calculate smoothed, standardized
      mortality rates for all homicides and homicides involving knives and other sharp
      objects, for all of Scotland and separately for Glasgow. Over half of homicides
      where the victim was male involved the use of a knife. Over 20 years, the
      homicide rate rose 83%, whilst that involving knives increased by 164%.
      CONCLUSION: The rapid increase in homicide involving knives is becoming a public
      health problem. Proposed changes to legislation are unlikely to halt this rise.

PMID- 16597628
TI  - The effects of surgical volumes and training centre status on outcomes following
      total joint replacement: analysis of the Hospital Episode Statistics for England.
AB  - OBJECTIVE: Previous work from other countries has shown a significant inverse
      relationship between the number of some surgical procedures undertaken in a
      hospital and in an adverse outcomes. In the light of the changing nature of the
      provision of joint replacements in the United Kingdom, we have examined the
      effects of surgical volumes and the presence/absence of training centre status,
      on outcomes following total joint replacement (TJR) in England. METHODS: Analysis
      of the Hospital Episode Statistics (HES) on all hip/knee joint replacements in
      English National Health Service (NHS) trusts between financial years 1997 and
      2002. Exposures explored were the volume of hip/knee replacements per annum in an
      NHS trust, training centre status and whether the admission was routine or
      emergency. Four surrogate measures of adverse outcome were assessed: 30-day in
      hospital mortality, length of stay in hospital, readmission within a year and
      surgical revision within 5 years. Age and sex were controlled for as potential
      confounders. RESULTS: Data from a total of 281 360 hip replacements and 211 099
      knee replacements were examined. HES data show that the numbers of TJRs performed
      in low volume trusts are small and decreasing. Adverse outcomes were also
      uncommon. Nevertheless, significant associations between adverse outcomes and low
      volume units, and better outcomes in training centres, were detected. For
      example, the odds ratio (OR) for in-hospital death within 30 days of hip
      replacement in trusts doing <50 hip/replacements per annum is 1.98 [95%
      confidence interval (95% CI) = 1.13-3.47] compared with trusts doing 251-500
      operations/annum. Similarly, surgery in non-training centres is more likely to
      result in mortality than that in training centres (OR = 1.25, 95% CI = 1.05
      1.48). The examination of surgical revision indicated adverse outcomes in higher
      volume units; this may be due to case-mix. CONCLUSION: In England, there are
      fewer adverse events following TJR in high volume centres and in orthopaedic
      training centres. Standardization of procedures may account for this finding. The
      data have implications for private practice in the United Kingdom and for the
      current move to undertake TJRs in Independent Sector Treatment Centres.

PMID- 16597629
TI  - Male hormonal contraception: concept proven, product in sight?
AB  - Current male hormonal contraceptive (MHC) regimens act at various levels within
      the hypothalamic pituitary testicular axis, principally to induce the withdrawal
      of the pituitary gonadotrophins and in turn intratesticular androgen production
      and spermatogenesis. Azoospermia or severe oligozoospermia result from the
      inhibition of spermatogonial maturation and sperm release (spermiation). All
      regimens include an androgen to maintain virilization, while in many the
      suppression of gonadotrophins/spermatogenesis is augmented by the addition of
      another anti-gonadotrophic agent (progestin, GnRH antagonist). The suppression of
      sperm concentration to 1 x 10(6)/ml appears to provide comparable contraceptive
      efficacy to female hormonal methods, but the confidence intervals around these
      estimates remain relatively large, reflecting the limited number of exposure
      years reported. Also, inconsistencies in the rapidity and depth of spermatogenic
      suppression, potential for secondary escape of sperm into the ejaculate and onset
      of fertility return not readily explainable by analysis of subject serum hormone
      levels, germ cell number or intratesticular steroidogenesis, are apparent. As
      such, a better understanding of the endocrine and genetic regulation of
      spermatogenesis is necessary and may allow for new treatment paradigms. The
      development of an effective, consumer-friendly male contraceptive remains
      challenging, as it requires strong translational cooperation not only between
      basic scientists and clinicians but also between public and private sectors. At
      present, a prototype MHC product using a long-acting injectable testosterone and
      depot progestin is well advanced.

PMID- 16597631
TI  - Oral nanoparticle-based antituberculosis drug delivery to the brain in an
      experimental model.
AB  - OBJECTIVES: To evaluate the potential of orally administered poly-lactide-co
      glycolide (PLG, a synthetic polymer) nanoparticle encapsulated antituberculosis
      drugs (ATDs) (rifampicin + isoniazid + pyrazinamide + ethambutol) for cerebral
      drug delivery in a murine model. METHODS: The formulation was prepared using the
      multiple emulsion technique and administered orally to mice for biodistribution,
      pharmacokinetic and chemotherapeutic studies. RESULTS: A single oral dose of the
      formulation to mice could maintain sustained drug levels for 5-8 days in the
      plasma and for 9 days in the brain. There was a significant improvement in the
      pharmacokinetic parameters such as mean residence time and relative
      bioavailability as compared with free drugs. The pharmacodynamic parameters such
      as the ratio of area under the curve to minimum inhibitory concentration
      (AUC/MIC) and the time up to which MIC levels were maintained in plasma (T(MIC))
      were also improved. In Mycobacterium tuberculosis H(37)Rv infected mice, five
      oral doses of the nanoparticle formulation administered every 10th day resulted
      in undetectable bacilli in the meninges, as assessed on the basis of cfu and
      histopathology. CONCLUSIONS: Polymeric nanoparticles bear significant potential
      for ATD delivery to the brain.

PMID- 16597632
TI  - Evolution of multidrug-resistant Acinetobacter baumannii isolates obtained from
      elderly patients with respiratory tract infections.
AB  - OBJECTIVES: To study the evolution between 1999 and 2002 and mechanisms of
      antibiotic resistance in a multidrug-resistant Acinetobacter baumannii clone
      predominant in isolates from elderly patients with respiratory tract infections.
      METHODS: Susceptibility to antimicrobials was determined using an agar dilution
      method. Bacterial clones were identified by PCR-fingerprinting and PFGE with
      ApaI. Carbapenemases were detected by phenotypic tests; by PCR with primers
      specific for bla (OXA-40), bla(IMP), bla(VIM-1) and bla(VIM-2); and by
      hybridization with DNA probes. Class 1 integrons were detected using PCR.
      RESULTS: In 1999 isolates were grouped into two main genotypes: clone I (33%) and
      clone II (55%). These were also detected in 2002 with a different distribution:
      clone I (69%), clone II (22%). Resistance to amikacin, meropenem and imipenem
      increased significantly in clone I over this time, whereas clone II was not
      affected. In 2002, the incidence of bla(OXA-40) rose to 91% in clone I isolates
      with some also harbouring bla(VIM-2) and bla(IMP) genes. Different class 1
      integrons were detected ranging in size from 550 to 1200 bp. No relationship was
      found between carbapenemases and class 1 integrons. CONCLUSIONS: In elderly
      patients, a single clone became predominant among A. baumannii isolates,
      coinciding with an increase in antibiotic resistance rates. The majority of
      isolates harboured the bla(OXA-40) carbapenemase gene and some of them also
      harboured bla(VIM-2) and bla(IMP) genes. The presence of class 1 integrons also
      increased over time.

PMID- 16597633
TI  - SmeDEF-mediated antimicrobial drug resistance in Stenotrophomonas maltophilia
      clinical isolates having defined phylogenetic relationships.
AB  - OBJECTIVES: To test whether smeDEF overexpression leads to a predictable multi
      drug resistance phenotype in Stenotrophomonas maltophilia and to measure the
      frequency with which smeDEF overexpression occurs in clinical isolates and in
      spontaneous drug-resistant mutants. METHODS: Overexpression of smeDEF was induced
      in clinical isolates by the introduction of chromosomal mutations in smeT using a
      gene-replacement approach. Spontaneous drug-resistant mutants were selected using
      greater than MIC concentrations of various antimicrobial agents. Levels of smeE
      and smeF mRNAs were quantified using RT-PCR; MICs were determined using Etest.
      RESULTS: Of 20 spontaneous S. maltophilia drug-resistant mutants tested, four
      overexpressed smeDEF, but only two carried mutations within smeT. Of 30 clinical
      isolates tested, 6 significantly overexpressed smeDEF. One of these had an IS1246
      like element embedded within the putative SmeT binding site in the smeDEF
      promoter. All smeDEF overexpressing derivatives of an isolate had the same
      resistance profile; derivatives that did not overexpress smeDEF did not share
      this resistance profile. However, no consistent phenotype could be associated
      with smeDEF overexpression in S. maltophilia isolates per se. CONCLUSIONS: SmeT
      is not the only gene product that affects smeDEF expression. IS element insertion
      is a viable mechanism by which smeDEF expression can be derepressed. There is
      evidence for a background-specific, predictable effect on resistance profile when
      smeDEF is overexpressed, but the variability of backgrounds encountered means no
      general SmeDEF-mediated phenotype can be defined. There is strong evidence for
      the existence of as yet unidentified multi-drug efflux pumps in this species.

PMID- 16597634
TI  - Antibiotic-lock therapy for long-term intravascular catheter-related bacteraemia:
      results of an open, non-comparative study.
AB  - BACKGROUND: Infection is one of the main problems associated with long-term
      central venous catheters. This study assesses the effectiveness of antibiotic
      lock therapy (ALT) for treating catheter-related bacteraemia (CRB). METHODS: CRB
      was defined as quantitative blood culture counts through any catheter lumen 5
      fold greater than concurrent peripheral blood culture, and qualitative blood
      culture positive for the same microorganism in all samples. Systemic treatment
      and ALT were started simultaneously using vancomycin (2000 mg/L) for Gram
      positive organisms, and ciprofloxacin or amikacin (2000 mg/L) for Gram-negative
      bacilli. Heparin was added to ALT. Effectiveness was assessed by clinical and
      microbiological criteria. Cure was defined as negative blood cultures at both
      sites without catheter removal at 1 month after the completion of therapy.
      RESULTS: A total of 115 episodes of CRB in 98 patients were analysed. Catheters
      were used for chemotherapy (50 episodes), haemodialysis (37), total parenteral
      nutrition (24) and combined chemotherapy and nutrition (4). Median time from
      catheter placement to CRB onset was 105 days (IQ range 26-210). Aetiologies
      included Gram-positive organisms [56 coagulase-negative staphylococci (CoNS), 20
      Staphylococcus aureus and 5 other organisms] in 81 episodes (70%), Gram-negative
      bacilli (11 Escherichia coli, 5 Pseudomonas aeruginosa and 10 other organisms) in
      26 (23%) and polymicrobial in 8 (7%). A total of 94 episodes were cured (82%).
      There were 21 therapeutic failures: 9 S. aureus (1 related death), 9 CoNS, 1 P.
      aeruginosa, 1 Proteus vulgaris and 1 polymicrobial. Median catheter follow-up in
      therapeutic success was 168 days (range 7-2740). CONCLUSIONS: ALT combined with
      systemic antibiotics seems to be effective for treating CRB, especially in Gram
      negative and CoNS episodes. S. aureus CRB had an elevated rate of therapeutic
      failure.

PMID- 16597635
TI  - First description of blaCTX-M-1-carrying Escherichia coli isolates in Danish
      primary food production.

PMID- 16597636
TI  - Risk factors for chronic transplant dysfunction and cardiovascular disease are
      related to accumulation of advanced glycation end-products in renal transplant
      recipients.
AB  - BACKGROUND: Accumulation of advanced glycation end-products (AGEs) has been
      implicated in the pathogenesis of chronic transplant dysfunction and
      cardiovascular disease in renal transplant recipients. We aimed to investigate
      which factors are associated with tissue AGE accumulation in renal transplant
      recipients. METHODS: The AGE accumulation was assessed using a validated skin
      autofluorescence reader (AFR) in 285 consecutive renal transplant recipients (57%
      male, aged 50+/-12 years) visiting the outpatient clinic at a median
      (interquartile range) time of 73 (32-143) months after transplantation.
      Furthermore, various transplant- and recipient-related factors of interest were
      collected. RESULTS: Average skin-autofluorescence of lower arm and leg was 2.7+/
      0.8 a.u. Skin-autofluorescence was positively determined by recipient age,
      systolic blood pressure, smoking, high-sensitivity C-reactive protein, duration
      of pre-transplant dialysis, and negatively by plasma vitamin C levels, creatinine
      clearance at baseline, and change in creatinine clearance since one year after
      transplantation in linear multivariate regression analysis. Together, these
      factors explained 41% of the variance of skin-autofluorescence. CONCLUSIONS: Skin
      autofluorescence was associated with several risk factors for cardiovascular
      disease and chronic renal transplant dysfunction. These results are in line with
      the hypothesis that AGEs play a role in the pathogenesis of these conditions in
      renal transplant recipients. Prospective studies are required to investigate
      whether the AFR can be used as a simple, non-invasive tool to identify and
      monitor patients at risk for chronic renal transplant dysfunction and
      cardiovascular disease.

PMID- 16597637
TI  - Glyoxylate reductase activity in blood mononuclear cells and the diagnosis of
      primary hyperoxaluria type 2.
AB  - BACKGROUND: Primary hyperoxaluria type 2 (PH2) is a rare monogenic disorder
      characterized by an elevated urinary excretion of oxalate. Increased oxalate
      excretion in PH2 patients can cause nephrolithiasis and nephrocalcinosis, and
      can, in some cases, result in renal failure and systemic oxalate deposition. The
      disease is due to a deficiency of glyoxylate reductase/hydroxypyruvate reductase
      (GRHPR) activity. A definitive diagnosis of PH2 is currently made by the analysis
      of GR activity in a liver biopsy. GRHPR is expressed in virtually every tissue in
      the body, suggesting that utilization of more readily available cells could be
      used to determine GRHPR deficiency. In this study, we have evaluated the
      potential of determining GR and d-glycerate dehydrogenase (DGDH) activity in
      blood mononuclear cells (BMC) as a diagnostic indicator of PH2. METHODS: Blood
      samples were obtained from 10 male and 10 female normal subjects, median age 31,
      range 21-63, at the Wake Forest University Medical Center and from primary
      hyperoxaluria patients at the Mayo Clinic. The BMC were isolated and GR and DGDH
      activities measured in cell lysates. RESULTS: An assay of 20 normal individuals
      indicated that BMC contained a DGDH and GR activity of 0.97+/-0.20 (range 0.62
      1.45), and 10.6+/-3.3 (range 8.3-16.6) nmol/min/mg protein, respectively. The
      intra-assay coefficient of variation for DGDH and GR activity was 8.2 and 11.5%,
      respectively. The BMC lysates from normal adult subjects and patients with PH1
      showed similar GR and DGDH activities. This was confirmed by the presence of
      immunoreactive GRHPR protein by western blot analysis. In contrast, PH2 BMC
      lysates did not exhibit DGDH or GR activity, and showed no immunoreactive GRHPR
      by western blot analysis. CONCLUSION: These results suggest that the assay of
      DGDH or GR activity in BMC could be used as a minimally invasive diagnostic test
      for PH2.

PMID- 16597638
TI  - Delta9-tetrahydrocannabinol inhibits cytotrophoblast cell proliferation and
      modulates gene transcription.
AB  - Cannabis use in pregnancy is associated with a range of obstetrical conditions.
      The molecular mechanisms underlying these effects have not been elucidated but
      are attributed to the actions of delta-9-tetrahydrocannabinol (Delta9-THC). In
      this study, concentrations of Delta9-THC equivalent to those found in the serum
      of cannabis users, i.e. approximately 20 microM, inhibited proliferation and
      activated a restricted tight transcriptional programme in the BeWo trophoblast
      cell line. Employing genome-wide expression profiling methods, we found that the
      pattern of gene expression differs from that described in the placenta of
      patients with fetal growth restriction (FGR), associated with either hypoxia or
      discordant dichorionic twins, or of patients with pre-eclampsia. It was also
      dissimilar to the patterns obtained from the transcriptome of other tissues, such
      as the mouse brain, treated with Delta9-THC. The expression of transcription
      factors, such as thyroid hormone receptor-beta1 (TRbeta1), and transcriptional co
      repressors, such as histone deactylase 3 (HDAC3), was affected by Delta9-THC in a
      dose-dependent manner, whereby 15 microM Delta9-THC caused a 2.8-fold inhibition
      of TRbeta1 expression, but a 3.5-fold increase in HDAC3 expression. These data
      were confirmed by end-point RT-PCR analyses and underpin the observed Delta9-THC
      induced inhibition of BeWo cell proliferation. Genes encoding for growth,
      apoptosis, cell morphology and ion exchange pathways were modulated by 15 microM
      Delta9-THC. This study may provide insight into the mechanisms underlying the
      effects of Delta9-THC and cannabis use upon placental development during
      pregnancy.

PMID- 16597639
TI  - cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian
      follicles.
AB  - Nobox is a homeobox gene that is preferentially expressed in the oocytes and is
      essential for folliculogenesis and the regulation of oocyte-specific gene
      expression in the mouse. The likely human homologue has been identified in silico
      but has not as yet been confirmed experimentally. Here, we present the first cDNA
      cloning and transcript expression analysis of the human NOBOX gene. Using RT-PCR,
      we reveal that expression within adult human tissues is limited to the ovary,
      testis and pancreas. Expression within the ovary is oocyte specific, with
      expression observed from the primordial stage ovarian follicle through to the
      metaphase II (MII) oocyte. In complementary studies, we reveal dynamic expression
      profiles of 14 additional homeobox genes throughout human oogenesis and early
      development. The expression of HOXA10 is restricted to primordial and early
      primary follicles. HOXB7 is expressed from primordial and early primary stage
      follicles through to germinal vesicle (GV) oocytes. Gastrulation brain homeobox 1
      (GBX1) and HOXA7 genes are homeobox markers preferentially expressed by GV
      oocytes. HOXA1 and HEX are homeobox markers preferentially expressed by MII
      oocytes. In summary, the homeobox gene transcripts that are detected in ovarian
      follicles and oocytes are distinct from those expressed in human blastocysts
      (HOXB4, CDX2 and HOXC9) and granulosa cells (HOXC9, HOXC8, HOXC6, HOXA7, HOXA5
      and HOXA4).

PMID- 16597640
TI  - No association found between gr/gr deletions and infertility in Brazilian males.
AB  - The Y chromosome carries several spermatogenesis genes distributed in three
      regions: AZFa, AZFb and AZFc. Microdeletions in these regions have been seen in
      10% of sterile males with azoospermia or oligozoospermia, the most frequent of
      them being characterized by a complete deletion of AZFc region. A partial AZFc
      deletion named gr/gr has been singled out as a risk factor for spermatogenic
      failure. However, other authors have diagnosed it as a polymorphic deletion with
      no clinical relevance. We decided to investigate the association of gr/gr
      deletion and infertility in Brazilian males. We analysed 350 individuals (110
      azoospermic, 122 fertile and 118 presumably fertile) and observed 12 g/gr
      deletions: five in infertile men (4.5%), three among fertile males (2.5%) and
      four in probably fertile individuals (3.4%). These differences were not
      statistically significant. Then, we decided to ascertain whether the clinical
      impact of the gr/gr deletion was associated with the type of Y chromosome. We
      have identified Y-chromosome haplogroups using 22 unique event polymorphisms
      (UEPs). Among the individuals with the gr/gr deletion, we found haplogroups R,
      K*, F*, E1, E3b2 and E3b*, all of which are common in white Brazilian males, and
      none revealed a particular association with infertility. Taken together, these
      results show no evidence of association between the occurrence of gr/gr deletion
      and male infertility.

PMID- 16597641
TI  - The role of the testis-specific gene hTAF7L in the aetiology of male infertility.
AB  - The X-linked TAF7L gene is homologous to the autosomal transcription factor TAF7.
      Together with its testis-specific expression pattern, this might point to an
      important function in spermatogenesis. In order to analyse the involvement of the
      hTAF7L gene in the aetiology of male infertility, a total of 25 patients with
      maturation arrest of spermatogenesis have been analysed for the presence of
      mutations in this gene. Four alterations of the nucleotide sequence, with
      concomitant changes in the amino acid sequence, have been observed in 12
      patients. All sequence alterations were also found either in a control group
      consisting of men with proven fertility or in a control group with men with
      normal spermatogenesis. Therefore, these alterations are probably polymorphisms.

PMID- 16597642
TI  - Enhancement of mammary carcinogenesis in two rodent models by silymarin dietary
      supplements.
AB  - Silymarin is a mixture of polyphenolic flavonoids isolated from milk thistle
      (Silybum marianum) with anticancer activities reported for several organ sites.
      The present study tested the efficacy of dietary silymarin against mammary
      carcinogenesis in two rodent models. In the Sprague-Dawley rat model, female rats
      were fed a purified diet supplemented with none, 0.03, 0.1, 0.3 or 1% (w/w) of
      silymarin from 21 days of age (DOA) and carcinogenesis was initiated by a single
      i.p. injection of 1-methyl-1-nitrosourea (MNU) at 51 DOA. Mammary tumor (MT)
      development was followed till 110 days after carcinogen injection. In the MMTV
      neu/HER2 transgenic mouse mammary carcinogenesis model, homozygous transgenic
      females were fed a purified diet supplemented with none or 0.3% silymarin, either
      from 28 or 120 DOA and MT development was followed to approximately 300 DOA. The
      results showed that dietary silymarin increased the plasma concentration of free
      and total silibinin, a major component of silymarin, in a dose-dependent manner
      in the rat, but did not decrease either MT incidence or number. Instead silymarin
      modestly increased the number of MNU-induced MTs in rats. Similarly, silymarin
      increased MT incidence and multiplicity and non-MTs in the neu-transgenic mice.
      In cell culture, treatment of human MCF-7 breast cancer cells with serum
      achievable concentrations of silymarin in the rodent models stimulated their
      growth, in part through an estrogen-like activity. Because silymarin is being
      used in the treatment of liver cirrhosis and a variety of other human ailments,
      and is sold as a dietary supplement, our findings add a cautionary note to its
      application in breast cancer prevention.

PMID- 16597643
TI  - Interleukin-6 production induced by leptin treatment promotes cell proliferation
      in an Apc (Min/+) colon epithelial cell line.
AB  - Increased visceral adipose tissue results in elevated plasma leptin, which are
      associated with increased risk of a number of obesity-related cancers. However,
      research is contradictory regarding the role of elevated plasma leptin in colon
      cancer risk. Having established that leptin induced proliferation in a murine
      model of preneoplastic (Apc(Min/+); IMCE) colon epithelial cells but not normal
      (Apc(+/+); YAMC) cells, we hypothesized that the leptin-associated IMCE cell
      proliferation was a result of autocrine interleukin-6 (IL-6) production and
      ensuing IL-6 receptor (IL-6R) signaling. Here we show, for the first time, that
      leptin induces elevated IL-6 production in IMCE cells but not in YAMC cells. IL-6
      treatment induced cell proliferation in IMCE cells, but not in YAMC cells, in a
      concentration-dependent manner from 0.1 to 100 ng/ml (P < 0.05). Interleukin-6
      induced IMCE cell proliferation was blocked by the addition of a neutralizing
      anti-IL-6R antibody. In addition, leptin-induced IMCE cell proliferation was
      blocked by the addition of an anti-IL-6R neutralizing antibody. Further, we
      elucidate a novel mechanism by which leptin activates TACE/ADAM17-associated IL
      6R shedding and trans-IL-6 signaling in IMCE by induction of IL-6 production. IL
      6 treatment of IMCE cells was associated with STAT3, ERK, p38, MEK and JAK2
      activation and associated STAT3 nuclear activation and translocation. These data
      implicate leptin-induced IL-6 production, signaling and subsequent STAT3
      activation as early events promoting the survival/proliferation of colon
      epithelial preneoplastic cells. The elucidation of the leptin-initiated mechanism
      of preneoplastic cell proliferation establishes a biologically plausible link
      between the adipocyte-specific cytokine leptin and obesity-associated colon
      cancer.

PMID- 16597644
TI  - Lymphatic vessels in cancer metastasis: bridging the gaps.
AB  - Distant organ metastasis is the most important factor in determining patient
      survival in cancer. This is thought to occur via the body's own systems for
      transporting fluid and cells, the blood vascular and lymphatic systems. Cancer
      cells may exploit these vascular systems by expressing growth factors, which
      alter the normal pattern of angiogenesis and lymphatic vessel growth
      (lymphangiogenesis), thus creating conduits for tumour metastasis. With respect
      to lymphatic metastasis, techniques which allow the mapping of a tumour's
      lymphatic drainage and sampling of the 'sentinel node' from the regional lymph
      node group provide crucial prognostic information, determine further treatment
      and offer a window into tumour-host immune interactions. Aberrant drainage
      patterns so identified are both clinically significant, and highlight important
      anatomical and molecular complexities not explained by existing models of
      lymphatic development or anatomy. The molecular controls of tumour
      lymphangiogenesis and factors determining which lymphatic vessel subtypes are
      induced may be targets for novel therapeutics designed to restrict cancer
      metastasis. Furthermore, analyses of these control mechanisms will enhance our
      understanding of the interactions between the tumour cells and the lymphatic
      vasculature. For many years, disparate groups of clinical researchers and basic
      scientists have been working to unravel the mysteries of the lymphatic system.
      This review aims to summarize these contributions, in terms of the history,
      identification, structure and function of lymphatic vessels in cancer and the
      role they play in tumour metastasis. Current ideas about the roles of
      lymphangiogenic growth factors, their signalling pathways in lymphatic metastasis
      and therapeutic opportunities to restrict this spread will also be explored.

PMID- 16597645
TI  - Grape seed proanthocyanidins induce apoptosis and inhibit metastasis of highly
      metastatic breast carcinoma cells.
AB  - The strategies available for the treatment of metastatic breast cancer are
      limited. Dietary botanicals may have a better protective effect on this disease.
      We therefore investigated the effects of grape seed proanthocyanidins (GSPs) on a
      highly metastatic mouse mammary carcinoma cell line. In vitro treatment of breast
      cancer cells, 4T1, MCF-7 and MDA-MB-468, with GSPs resulted in significant
      inhibition of cellular proliferation and viability, and induction of apoptosis in
      4T1 cells in a time- and dose-dependent manner. Further analysis indicated an
      alteration in the ratio of Bax/Bcl-2 proteins in favor of apoptosis, and the
      knockdown of Bax using Bax siRNA transfection of 4T1 cells resulted in blocking
      of GSPs-induced apoptosis. Induction of apoptosis was associated with the release
      of cytochrome c, increased expression of Apaf-1 and activation of caspase 3 and
      poly (ADP-ribose) polymerase. Treatment with the pan-caspase inhibitor (Z-VAD
      FMK) resulted in partial but significant inhibition of apoptosis in 4T1 cells
      suggesting the involvement of both caspase activation-dependent and activation
      independent pathways in the apoptosis of 4T1 cells induced by GSPs. The effects
      of dietary GSPs were then examined using an in vivo model in which 4T1 cells were
      implanted subcutaneously in Balb/c mice. Dietary GSPs (0.2 and 0.5%, w/w)
      significantly inhibited the growth of the implanted 4T1 tumor cells and increased
      the ratio of Bax:Bcl-2 proteins, cytochrome c release, induction of Apaf-1 and
      activation of caspase 3 in the tumor microenvironment. Notably, the metastasis of
      tumor cells to the lungs was inhibited significantly and the survival of the mice
      enhanced. These data suggest that GSPs possess chemotherapeutic efficacy against
      breast cancer including inhibition of metastasis.

PMID- 16597646
TI  - Most spontaneous tumors in a mouse model of Li-Fraumeni syndrome do not have a
      mutator phenotype.
AB  - Mutations are the substrate of cancer. Yet, little is known about the degree and
      nature of mutations in tumors because measurement of mutation load in tumors and
      normal tissues was generally not possible until the advent of transgenic mouse
      mutation detection systems. Herein, we present the first analysis of mutation
      frequency and pattern in thymic tumors from a mouse model of Li-Fraumeni syndrome
      (p53+/- murine model) using the Big Blue assay with sequencing of all mutants. We
      also make the first characterization of mutation frequency and pattern in p53
      deficient extra-thymic cancers. The data more than triple the literature on all
      non-mismatch repair deficient tumors for which mutations are identified by
      sequence analysis, allowing mutation frequency and pattern to be determined. Most
      tumors had a normal mutation frequency and a normal mutation pattern. Five tumors
      showed modest increases in mutation frequency (2.3-fold or less). Alterations in
      mutation patterns were uncommon, tumor-specific and not necessarily associated
      with increases in mutation frequency. Given the data from two spontaneous tumors
      (normal mutation frequency with an abnormal pattern in a p53-/- mouse and low
      mutation frequency in a p53+/+ control mouse), we hypothesize that tumors
      sometimes can carry a low mutation load. The study was not without certain
      caveats: mutation load could not be compared between tumor and normal tissue from
      the same animal; sample sizes for extra-thymic tumor types were small, and only
      point mutations and deletions, insertions and indels up to 2 kb were detected.
      However, the data clearly show key differences in tumors from p53+/- mice
      compared with mismatch repair deficient tumors; a lack of dramatic increase in
      mutation frequency and absence of a signature of mutation.

PMID- 16597647
TI  - GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells.
AB  - Celecoxib, a selective cyclooxygenase-2 inhibitor, is known to possess anti
      inflammatory activity and also induces apoptosis in various types of cancer
      cells. Here, we examined the molecular mechanism of celecoxib-induced apoptosis
      in cervical cancer cell lines (HeLa, CaSki and C33A). Screening of a cDNA
      microarray chip containing 225 different genes revealed that GADD153 (growth
      arrest and DNA damage inducible gene), a transcription factor involved in
      apoptosis, showed the strongest differential expression following celecoxib
      treatment in all three cervical cancer cell lines. Notably, siRNA-induced
      silencing of GADD153 suppressed celecoxib-induced apoptosis in all three cell
      lines, and exogenous expression of GADD153 triggered apoptosis in cervical cancer
      cells in the absence of other apoptotic stimuli. A luciferase reporter gene assay
      and mRNA stability tests revealed that the expression of GADD153 was regulated at
      both the transcriptional and post-transcriptional levels following celecoxib
      treatment. The region between -649 and -249, containing an intact C/EBP-ATF
      binding site, is required for celecoxib-induced stimulation of GADD153 promoter
      activity. In terms of signaling pathway, addition of the NF-kappaB inhibitor, N
      tosyl-L-phenylalanyl-chloromethyl ketone, had no effect on GADD153 expression
      levels. Celecoxib treatment induced Bak expression, whereas cell transfected with
      siGADD153 showed lower levels of celecoxib-induced Bak upregulation. These novel
      findings collectively suggest that GADD153 may play a key role in celecoxib
      induced apoptosis in cervical cancer cells by regulating the expression of
      proapoptotic proteins such as Bak.

PMID- 16597648
TI  - Dietary resistant starch type 3 prevents tumor induction by 1,2-dimethylhydrazine
      and alters proliferation, apoptosis and dedifferentiation in rat colon.
AB  - Some epidemiological and experimental studies suggest that consumption of
      resistant starch is preventive against colon cancer. Resistant starch leads to a
      fermentation-mediated increase in the formation of short-chain fatty acids, with
      a particularly high butyrate fraction in large bowel. Butyrate is considered to
      be protective against colon cancer because it causes growth arrest and apoptosis
      and regulates expression of proteins involved in cellular dedifferentiation in
      various tumor cell lines in culture. We sought to investigate these processes
      under conditions of a carcinogenicity experiment in vivo. In the present study,
      1,2-dimethylhydrazine-treated Sprague-Dawley rats were fed standard diet (n=12)
      or diet with 10% hydrothermally modified Novelose 330, a resistant starch type 3
      (RS3), replacing digestible starch (n=8). After 20 weeks tumor number, epithelial
      proliferation, apoptosis, immunoreactivity of carcinogenesis-related proteins
      [protein kinase C-delta (PKC-delta), heat shock protein 25 (HSP25) and
      gastrointestinal glutathione peroxidase (GI-GPx)], as well as mucin properties
      were evaluated in proximal and distal colon in situ. No tumors developed under
      RS3 diet, compared to a tumor incidence of 0.6+/-0.6 (P<0.05) under the standard
      diet. RS3 decreased the number of proliferating cells, the length of the
      proliferation zone and the total length of the crypt in the distal colon, but not
      proximal colon, and enhanced apoptosis in both colonic segments. It induced PKC
      delta and HSP25 expression, but inhibited GI-GPx expression in the epithelium of
      distal colon. RS3 increased the number of predominantly acidic mucin containing
      goblet cells in the distal colon, but had no effect on the goblet cell count. We
      conclude that hydrothermally treated RS3 prevented colon carcinogenesis, and that
      this effect was mediated by enhanced apoptosis of damaged cells accompanied by
      changes in parameters of dedifferentiation in colonic mucosa.

PMID- 16597649
TI  - Correlates of sleep-onset REM periods during the Multiple Sleep Latency Test in
      community adults.
AB  - The diagnosis of narcolepsy without documented cataplexy is based on the
      observation of two or more sleep-onset REM periods (SOREMPs) during the Multiple
      Sleep Latency Test (MSLT). We report on the prevalence and correlates of SOREMPs
      in the community-based Wisconsin Sleep Cohort Study. MSLTs were conducted
      following nocturnal polysomnography (NPSG) and daily sleep diaries in 289 males
      and 267 females (age 35-70, 97% Caucasians). Multiple SOREMPs were observed in
      13.1% of males and 5.6% of females. An MSLT mean sleep latency < or =8 min and >
      or =2 SOREMPs (diagnostic of narcolepsy) was observed in 5.9% (males) and 1.1%
      (females), all without cataplexy. Because of significant sex interactions,
      analyses were stratified by sex. Increased prevalence of HLA-DQB1*0602, a marker
      of narcolepsy, was observed in males but not in females with > or =2 SOREMPs.
      Males with multiple SOREMPs compared with those with no SOREMPs had shorter rapid
      eye movement (REM) latency during NPSG, were sleepier on the MSLT and reported
      increased sleepiness, hypnagogic hallucinations and cataplexy-like symptoms,
      suggesting a narcolepsy-like phenotype. In males only, the occurrence of SOREMPs
      increased with shift work and some indirect markers of sleep restriction, such as
      shorter sleep a day before NPSG. SOREMPs were unrelated to age, body mass index,
      depression (Zung Scale), anxiety (State-Trait Anxiety Scale) and the number of
      apnea and hypopnea events per hour of sleep (AHI), but were associated with
      decreased mean lowest oxygen saturation in males. Finally, we found that both
      males and females with SOREMPs reported taking more antidepressants, but those
      were of the types known not to suppress REM sleep. These results suggest a high
      prevalence of narcolepsy without cataplexy, as defined by the International
      Classification of Sleep Disorders, and/or a large number of false-positives for
      the MSLT.

PMID- 16597650
TI  - Phenotypic heterogeneity in inherited prion disease (P102L) is associated with
      differential propagation of protease-resistant wild-type and mutant prion
      protein.
AB  - Inherited prion diseases are caused by PRNP coding mutations and display marked
      phenotypic heterogeneity within families segregating the same pathogenic
      mutation. A proline-to-leucine substitution at prion protein (PrP) residue 102
      (P102L), classically associated with the Gerstmann-Straussler-Scheinker (GSS)
      phenotype, also shows marked clinical and pathological heterogeneity, including
      patients with a Creutzfeldt-Jakob disease (CJD) phenotype. To date, this
      heterogeneity has been attributed to temporal and spatial variance in the
      propagation of distinct protease-resistant (PrP(Sc)) isoforms of mutant PrP.
      Here, using a monoclonal antibody that recognizes wild-type PrP, but not PrP
      102L, we reveal a spectrum of involvement of wild-type PrP(Sc) in P102L
      individuals. PrP(Sc) isoforms derived from wild-type and mutant PrP are distinct
      both from each other and from those seen in sporadic and acquired CJD. Such
      differential propagation of disease-related isoforms of wild-type PrP and PrP
      102L provides a molecular mechanism for generation of the multiple
      clinicopathological phenotypes seen in inherited prion disease.

PMID- 16597651
TI  - The contribution of demyelination to axonal loss in multiple sclerosis.
AB  - The traditional notion that multiple sclerosis is a primary demyelinating disease
      has led to a plaque-centred view of both aetiology and the pathogenesis of
      disease progression. The presence of axonal loss has received increasing
      recognition. However, the relative roles of demyelination and axonal loss have
      not been fully clarified in multiple sclerosis nor have their possible
      interrelationships been elucidated. Post-mortem material from the cerebrum,
      brainstem and spinal cord of 55 multiple sclerosis patients (29 males) with an
      age range of 25-83 years (mean = 57.5 years) and length of disease history
      ranging from 2 to 43 years (mean = 17.1 years) was stained for myelin. Plaque
      load was calculated by summing the relative proportion of plaque area compared
      with total white matter area of the corticospinal and sensory tracts at each
      level. This was related to estimates of axonal density and of total axon number
      in these tracts in the spinal cord. Our results indicate that plaque load did not
      correlate with brain weight. Unexpectedly, after adjusting for sex, age and
      duration of disease, correlations between total plaque load and axonal loss in
      both the corticospinal tract and sensory tracts were weak or absent at each level
      investigated. Since there was little correlation between plaque load and axonal
      loss, the possibility that demyelination is not the primary determinant of spinal
      cord axonal loss warrants consideration.

PMID- 16597652
TI  - Cognitive mechanisms, specificity and neural underpinnings of visuospatial peaks
      in autism.
AB  - In order to explain the cognitive and cerebral mechanisms responsible for the
      visuospatial peak in autism, and to document its specificity to this condition, a
      group of eight high-functioning individuals with autism and a visuospatial peak
      (HFA-P) performed a modified block-design task (BDT; subtest from Wechsler
      scales) at various levels of perceptual cohesiveness, as well as tasks tapping
      visuomotor speed, global perception, visual memory, visual search and speed of
      visual encoding. Their performance was compared with that of 8 autistics without
      a visuospatial peak (HFA-NP), 10 typically developing individuals (TD) and 8
      gifted comparison participants with a visuospatial peak (TD-P). Both HFA-P and
      HFA-NP groups presented with diminished detrimental influence of increasing
      perceptual coherence compared with their BDT-matched comparison groups. Neither
      autistic group displayed a deficit in construction of global representations. The
      HFA-P group showed no differences in performance level or profile in comparison
      with the gifted BDT-matched [i.e. higher full-scale IQ (FSIQ)] group, apart from
      locally oriented perception. Diminished detrimental influence of perceptual
      coherence on BDT performance is both sensitive and specific to autism, and
      superior low-level processing interacts with locally oriented bias to produce
      outstanding BDT performance in a subgroup of autistic individuals. Locally
      oriented processing, enhanced performance in multiple tasks relying on detection
      of simple visual material and enhanced discrimination of first-order gratings
      converge towards an enhanced functioning and role of the primary visual cortex
      (V1) in autism. In contrast, superior or typical performance of autistics in
      tasks requiring global processing is inconsistent with the global-deficit-driven
      Weak Central Coherence hypothesis and its neurobiological magnocellular deficit
      counterpart.

PMID- 16597654
TI  - The craniopagus malformation: classification and implications for surgical
      separation.
AB  - Craniopagus twins (CPT) are an uncommon, highly fascinating accident of nature.
      The clinical pathology of this complex entity is reviewed and placed in
      perspective. A logical classification aids understanding of the anomaly, and is
      essential to gauge outcome from separation attempts. 'Partial forms' lack
      significant shared dural venous sinuses (SDVS) and 'Total forms' with SDVS also
      exhibit more severe compressional brain distortion. Our classification consists
      of Partial Angular (PA), Partial Vertical (PV), Total Angular (TA) and Total
      Vertical (TV, formerly O'Connell Types I-III). Total vertical has a continuous
      cranium, and inter-twin axial facial rotation <40 degrees (Type I), 140-180
      degrees (Type II) or intermediate (Type III). The term 'Angular' denotes an inter
      twin longitudinal angle below 140 degrees , regardless of axial rotation. Our
      review categorized 64 well-delineated CPT, including 41 operative separation
      attempts in small children since initial success in 1952. Just over one-half were
      TV, almost one-third TA, and partial forms accounted for the remaining one-sixth.
      About 30% of CPT had shared or fused brain tissue, and a similar percentage of TA
      twins shared a posterior fossa. Partial forms had significantly higher birth
      weights, were separated at an earlier age (6 versus 11 months) and had lower
      mortality and better outcome compared with Total forms. A multi-staged surgical
      separation for Total CPT had a significantly better mortality than single-staged
      separation. Discussion emphasizes embryological, anatomical and clinical aspects
      of the malformation, with emphasis upon obstacles to a successful outcome.

PMID- 16597653
TI  - Impaired anticipatory control of fingertip forces in patients with a pure motor
      or sensorimotor lacunar syndrome.
AB  - We examined planning and execution of precision grasp in eight right-handed
      patients with a right pure motor or sensorimotor lacunar syndrome after a
      subcortical stroke and eight age-matched controls as they grasped and lifted an
      instrumented object whose weight could be varied without altering its visual
      appearance. Grip (normal) and load (tangential) forces at the fingertip-object
      interface were measured and the grip force rate (GFR) and load force rate (LFR)
      were derived. Planning of precision grasp was assessed by measurement of
      anticipatory scaling of peak GFR and peak LFR to object weight. Execution of
      precision grasp was assessed by measurement of both the timing and efficiency of
      grip-load force coordination: the pre-load phase duration (PLD) and the load
      phase duration (LPD) measured timing, whereas the grip force at load force onset
      (GFO) and the grip force at lift-off (GFL) measured efficiency. Subjects lifted a
      light and heavy object five times first with the RIGHT hand, then with the LEFT
      hand, and then once more with the RIGHT AFTER LEFT hand. Patients with stroke did
      not scale the peak LFR or peak GFR to object weight with the RIGHT hand even with
      repeated attempts; however, they scaled the peak LFR to object weight on the
      first lift with the RIGHT AFTER LEFT hand (P = 0.01). Patients also prolonged the
      PLD and LPD and produced excessive GFO and GFL for RIGHT hand lifts, but
      decreased the GFL for the heavy object (P = 0.016) with the RIGHT AFTER LEFT
      hand. Correlation of precision grasp variables from lifts with the RIGHT hand
      with clinical measures showed that anticipatory scaling of peak LFR and peak GFR
      did not correlate with clinical measures of hand function, whereas the PLD did (r
      = 0.88, P = 0.004). The results suggest that patients with right hemiparesis from
      a subcortical lesion of the corticospinal tract have a higher-order motor
      planning deficit. This planning deficit is dissociable from deficits in motor
      execution, is not captured by routine clinical assessment, and is correctable by
      transfer of information from the unaffected hemisphere. A rehabilitation strategy
      that involves practice with the left hand prior to practice with the right hand
      may improve planning of grasping behaviour in patients with right hemiparesis.

PMID- 16597656
TI  - XRCC1 protects against particulate chromate-induced chromosome damage and
      cytotoxicity in Chinese hamster ovary cells.
AB  - Water-insoluble hexavalent chromium compounds are well-established human lung
      carcinogens. Lead chromate, a model insoluble Cr(VI) compound, induces DNA
      damage, chromosome aberrations, and dose-dependent cell death in human and
      Chinese hamster ovary (CHO) cells. The relationship between lead chromate-induced
      DNA damage and chromosome aberrations is unknown. Our study focus was on
      examining the role of XRCC1 in lead chromate-induced cytotoxicity and structural
      chromosomal aberrations in CHO cells. Three different cell lines were used: AA8
      (parental), EM9 (XRCC1 mutant), and H9T3 (EM9 complemented with human XRCC1
      gene). Cytotoxicity was significantly higher in EM9 cells when compared to AA8
      and H9T3 cells, indicating that XRCC1 is important for protecting cells from lead
      chromate particles-induced cell death. The frequency of damaged metaphase cells
      was not affected by XRCC1 deficiency. However, the total amount of Cr(VI)-induced
      chromosome damage was exacerbated by XRCC1 deficiency, and the spectrum of damage
      changed dramatically. Chromatid and isochromatid lesions were the most prominent
      aberrations induced in all cell lines. XRCC1 was essential to reduce the
      formation of chromatid lesions, but not for isochromatid lesions. In addition,
      XRCC1 deficiency resulted in a dramatic increase in the number of chromatid
      exchanges, indicating that XRCC1 is involved in protection from lead chromate
      induced chromosome instability.

PMID- 16597655
TI  - Study of the prophylactic effect of droperidol, alizapride, propofol and
      promethazine on spinal morphine-induced pruritus.
AB  - BACKGROUND: We have compared the use of alizapride, propofol, droperidol and
      promethazine for the prevention of spinal morphine-induced pruritus. METHODS:
      Three hundred ASA I or II women undergoing Caesarean section under spinal
      anaesthesia, in which morphine 0.2 mg was added to a local anaesthetic, were
      assigned randomly to receive i.v., in the operating room, just after delivery of
      the baby, alizapride 100 mg, propofol 20 mg, droperidol 1.25 mg, promethazine 50
      mg or saline 2 ml (control group). In the postoperative period, the women were
      assessed for pruritus (absent, mild, moderate or severe) or other untoward
      symptoms by blinded observers. We used 95% confidence limits (95% CI) for the
      cumulative incidence of moderate and severe pruritus to compare the groups, and
      the NNT and 95% CI to compare droperidol, propofol and alizapride as for their
      effectiveness in preventing pruritus. For other untoward effects, the chi(2)-test
      was used, results being considered significant when P<0.05. RESULTS: The
      droperidol, propofol and alizapride groups had significantly lower incidences of
      pruritus compared with the control and promethazine groups, while the incidence
      of pruritus was similar among the patients assigned to the promethazine and
      control groups. As for the prevention of moderate and severe pruritus, droperidol
      had the lowest NNT (3.52; 95% CI: 3.37-3.67), followed by propofol (4.61; 95% CI:
      4.45-4.77) and alizapride (5.43; 95% CI: 5.27-5.59). As for untoward effects,
      droperidol and promethazine increased the incidence of somnolence, which seemed
      more severe with promethazine. Otherwise, there were no differences between the
      groups. CONCLUSION: Droperidol, propofol and alizapride, in a decreasing order of
      effectiveness in the doses used in this study, reduced the incidence of pruritus
      induced by the use of morphine 0.2 mg intrathecally. On the other hand,
      promethazine 50 mg was shown to be ineffective.

PMID- 16597657
TI  - Tracheobronchial particle dose considerations for in vitro toxicology studies.
AB  - The purpose of this paper is to present a method for estimating particle doses
      that may be used to reconcile particle deposition doses used in in vitro
      toxicology studies with in vivo exposure levels. The focus is on the
      tracheobronchial (TB) tree of heavily exposed individuals. A review of the
      factors that influence inhaled particle deposition doses in environmental
      exposures leads to the identification of cases in which greater than average TB
      tree doses are received. Exercising individuals and those with chronic
      obstructive pulmonary disease not only inhale increased volumes of air but they
      also may have uneven ventilation that leads to greater than average particle
      deposition doses per unit of TB tree surface area. In addition, deposition hot
      spots, as occur at airway bifurcations, will greatly increase the particle
      exposures of target cells in the TB tree. Three particle exposure scenarios are
      proposed, and the average and local doses to the TB epithelium are calculated.
      When various factors that enhance particle doses (enhancement factors, or EFs) in
      vivo are considered, substantial particle doses may be justified for in vitro
      tissue culture studies that use TB target cells, such as epithelial cell
      cultures. The use of such EFs is intended to improve in vitro dosing with
      particles. Although the exposure of cells in vitro cannot fully replicate the
      complexity of in vivo exposures, it is possible to calculate toxicologically
      relevant doses that may define adverse health effects in potentially sensitive
      human populations. Local groups of TB cells in high-dose individuals are
      predicted to receive particle doses that are 3000-25,000 times higher than the
      doses averaged over the entire TB region.

PMID- 16597658
TI  - T-cell recognition of glycolipids presented by CD1 proteins.
AB  - The most well-known molecular paradigm of antigen recognition by T cells involves
      partial digestion of proteins to generate small peptides, which bind to major
      histocompatibility complex (MHC) proteins. Recent studies of CD1, an MHC class I
      homolog encoded outside the MHC, have revealed that it presents diverse
      glycolipids to T cells. The molecular mechanism for lipid antigen recognition
      involves insertion of the lipid portion of antigens into a hydrophobic groove to
      form CD1-lipid complexes, which contact T-cell receptors (TCRs). Here, we examine
      the known antigen structures presented by CD1, the majority of which have sugar
      moieties that are capable of interacting with TCRs. Recognition of carbohydrate
      epitopes is precise, and lipid-reactive T cells alter systemic immune responses
      in models of infectious and autoimmune disease. These findings provide a
      previously unrecognized mechanism by which the cellular immune system can
      recognize alterations in many types of carbohydrate structures.

PMID- 16597659
TI  - hOGG1 recognizes oxidative damage using the comet assay with greater specificity
      than FPG or ENDOIII.
AB  - The European Standards Committee on Oxidative DNA Damage (ESCODD) recommended the
      use of the lesion-specific repair enzyme, formamidopyrimidine DNA-glycosylase
      (FPG) in the comet assay to detect oxidative DNA damage. In the present study,
      FPG was compared with endonuclease III (ENDOIII) and human 8-hydroxyguanine DNA
      glycosylase (hOGG1) for the ability to modify the sensitivity of the comet assay.
      Mouse lymphoma L5178Y cells were treated with dimethyl sulphoxide (DMSO) as a
      standard solvent or reference agents known to induce oxidative damage (gamma
      irradiation and potassium bromate) or alkylation (methyl methanesulfonate, MMS;
      ethylnitrosurea, ENU). Using DMSO even up to toxic concentrations, no increase in
      breaks was seen with FPG, ENDOIII or hOGG1. With gamma irradiation (1-10 Gy),
      dose-related increases in breaks were seen with all three enzymes. FPG and hOGG1
      gave similar increases in breaks after potassium bromate treatment between 0.25
      and 2.5 mmol/l, but ENDOIII showed an increase only at the highest concentration,
      2.5 mmol/l. Following MMS treatment (5-23 micromol/l), FPG induced a dramatic
      increase in breaks compared with control levels and ENDOIII also showed a
      significant but smaller increase; in marked contrast, hOGG1 gave no increase.
      With ENU (0.5-2.0 mmol/l), increases in breaks were seen with FPG and ENDOIII at
      1 and 2 mmol/l but, again, no increase was observed with hOGG1. These data
      indicate that all three endonucleases recognize oxidative DNA damage and, in
      addition, FPG and ENDOIII also recognize alkylation damage. Therefore, caution
      should be taken when using FPG and ENDOIII in the comet assay with an agent that
      has an unknown mode of action since any additional strand breaks induced by
      either enzyme cannot necessarily be ascribed to oxidative damage. The use of
      hOGG1 in the modified comet assay offers a useful alternative to FPG and is
      apparently more specific for 8-oxoguanine and methyl-fapy-guanine.

PMID- 16597660
TI  - Effect of different forms of information produced for cancer patients on their
      use of the information, social support, and anxiety: randomised trial.
AB  - OBJECTIVE: To explore the hypothesis that different methods of selecting and
      printing information for cancer patients could improve emotional support by
      affecting interaction with others, and so lead to improved psychological
      wellbeing. DESIGN: Randomised trial with eight groups (three factors, 2x2x2).
      Data collected at recruitment and three month follow-up. PARTICIPANTS: 400
      patients starting radiotherapy, of whom 325 with breast or prostate cancer and
      complete anxiety and depression data were included in the analysis.
      INTERVENTIONS: Printed booklets: half had only general information from
      CancerBACUP about each patient's cancer and half had personalised information
      from the patient's medical record plus selected general information; half were
      composed of information chosen interactively by the patient and half were
      produced automatically with a larger volume of material; and half had additional
      advice on anxiety management and half did not. MAIN OUTCOME MEASURES: Patients'
      views of the information, use of their booklets with others; change in reported
      social support; change in anxiety and depression. RESULTS: The larger booklets
      produced automatically were more likely to be found useful and to tell patients
      something new and less likely to be seen as too limited than the booklets
      produced interactively, but they were also more likely to overwhelm some
      patients. Personalised booklets were more likely than general booklets to tell
      patients something new. There was no difference in patients' perceived
      understanding of their cancer by any of the intervention factors. Patients with
      personalised information were more likely to show their booklets to others and to
      think it helped in discussing their cancer or its treatment. There were no major
      differences in social support, anxiety, or depression by any intervention
      factors. CONCLUSIONS: Patients were more likely to show personalised information
      to their confidants than general information. Further research is needed into the
      effects of sharing information on patients' social support and anxiety. Trial
      registration US Government Clinical Trials Database NCT00127465.

PMID- 16597661
TI  - Long term results of primary posterior chamber intraocular lens implantation for
      congenital cataract in the first year of life.
AB  - AIM: To document the long term outcome of congenital cataract surgery with
      primary posterior chamber (PC) lens implantation in the first year of life.
      METHOD: A retrospective review of congenital cataract surgery in the first year
      of life with PC lens implantation in 18 infants, eight with unilateral and 10
      with bilateral cataract. The average age at surgery was 15 weeks (range 3-44
      weeks). The mean follow up was 95 months (range 60-139 months). RESULTS: The best
      outcomes were in the bilateral group where 50% of eyes achieved 6/18 or better,
      with a best acuity of 6/9. Acuities were poor in the unilateral group where only
      38% achieved 6/60 or better, with a best acuity of 6/24. There was a mean
      refractive shift between first refraction after surgery and refraction at 36
      months after surgery of -3.44 dioptres with a very wide range (+2.00 to -15.50).
      There was a significantly greater myopic shift in the unilateral cases. Many eyes
      in both groups continued to show an increasing myopic shift between 36 months
      after surgery and their final recorded refraction. The main complications were
      amblyopia, especially in unilateral cataracts, and posterior capsular
      opacification. Amblyopia was most probably related to a combination of early
      onset of dense cataract in this young age group, late presentation for initial
      surgery, delay in capsulotomies, and imperfect compliance with a rigorous
      occlusion regime. CONCLUSION: Intraocular lens implantation in infants less than
      1 year of age is generally a safe procedure. The spread of final refractive error
      was very wide. Final refraction in the unilateral group was significantly more
      myopic than the bilateral group. Final acuities were often disappointing
      especially in the unilateral group.

PMID- 16597662
TI  - Visual function in patients with yellow tinted intraocular lenses compared with
      vision in patients with non-tinted intraocular lenses.
AB  - AIM: To compare the visual function in patients with short wavelength blue light
      blocking yellow tinted intraocular lenses (IOLs) with that in patients with non
      tinted IOLs. METHODS: 74 patients scheduled for bilateral cataract surgery
      underwent implantation of either yellow IOLs (HOYA YA60BB) or non-tinted IOLs
      (VA60BB) in both eyes. Contrast visual acuity with and without a glare source was
      measured under photopic (100 cd/m2) and mesopic (slightly higher luminance than
      typically used-5 cd/m2) conditions at 2 weeks and 3 months after surgery using
      the contrast sensitivity accurate tester. Visual acuity and the incidence of
      patients who noted cyanopsia were also examined. RESULTS: No significant
      differences between the yellow tinted and non-tinted IOL groups were observed in
      mean visual acuity or in photopic or higher luminance mesopic contrast visual
      acuity with and without glare source at either 2 weeks or 3 months after surgery.
      Furthermore, there was no significant difference in contrast visual acuity loss
      as a result of glare. The incidence of patients who noticed cyanopsia was
      significantly less in the yellow tinted IOL group than in the non-tinted IOL
      group at 2 weeks after surgery (p = 0.0234), but no patients reported cyanopsia
      at 3 months. CONCLUSION: Visual function in patients with yellow tinted IOLs is
      virtually the same as that in patients with non-tinted IOLs.

PMID- 16597663
TI  - Localisation of SDF-1 and its receptor CXCR4 in retina and choroid of aged human
      eyes and in eyes with age related macular degeneration.
AB  - AIM: To examine the immunolocalisation of stromal cell derived factor 1 (SDF-1)
      and its receptor CXCR4 in aged control human donor eyes and eyes with age related
      macular degeneration (AMD). METHODS: Postmortem eyes from eight aged control
      donors (mean age 79.8 years) and from 12 donors with AMD (mean age 83.9 years)
      were cryopreserved and sectioned through the macular region. SDF-1 and CXCR4 were
      localised using streptavidin alkaline phosphatase immunohistochemistry and then
      sections were bleached. Three independent masked observers scored the
      immunohistochemical reaction product. RESULTS: In aged control retinas, SDF-1
      immunoreactivity was most intense in inner photoreceptor matrix (IPM). CXCR4
      showed a similar pattern of immunostaining, but was more prominent in inner
      segments of photoreceptors. In aged control and AMD choroid, SDF-1 and CXCR4
      localisations were most prominent in retinal pigment epithelial (RPE) cells and
      choroidal stroma. However, the intensity for SDF-1 was significantly reduced in
      RPE (p < 0.0001) and choroidal stroma (p < 0.05) in late AMD eyes. SDF-1 and
      CXCR4 immunoreactivities were weak or nearly absent in disciform scars with
      choroidal neovascularisation (CNV). Circulating cells, presumably leucocytes,
      were most intensely positive for CXCR4. CONCLUSIONS: These results show that
      changes in distribution and relative levels of SDF-1/CXCR4 were not evident in
      early AMD. This suggests that SDF-1/CXCR4 may not contribute to the formation of
      CNV in AMD, in that CXCR4+ cells were not incorporated into neovascularisation.
      However, the examples of CNV studied were within disciform scars, so the authors
      cannot comment on the role of SDF-1/CXCR4 in the early stages of CNV formation.

PMID- 16597664
TI  - Intraocular pressure alterations following intravitreal triamcinolone acetonide.
AB  - AIMS: To determine the prevalence of intraocular pressure (IOP) alterations
      following intravitreal injection of triamcinolone acetonide (IVTA) and to assess
      possible risk factors of IOP elevation in eyes receiving single and/or repeat
      injections. METHODS: Retrospective, consecutive case series. 570 consecutive eyes
      of 536 patients who received a single IVTA injection (4 mg/0.1 ml) and a second
      set of 43 eyes of 40 patients who received a second injection. Retrospective
      review of all IVTA cases performed by three vitreoretinal surgeons over a 42
      month period beginning in 2000. The main outcome measure was change in IOP
      defined as absolute value of IOP elevation (5 mm Hg or higher, 10 mm Hg or
      higher), and percentage of baseline (30% or higher increase from baseline IOP).
      RESULTS: Of the 528 eyes receiving single injections, 281 (53.2%) had an IOP
      elevation; 267 eyes (50.6%) experienced an elevation of IOP of at least 30%, and
      245 (45.8%) and 75 (14.2%) eyes had an increase of 5 mm Hg or 10 mm Hg or more,
      respectively. Baseline IOP greater than 16 mm Hg is a risk factor for post
      injection IOP elevation. Of the 43 eyes which received a second injection, 28
      (65.1%) experienced an increase in IOP of at least 30% of baseline. Filtering
      surgery was required in five (0.094%) of the single and one (2.3%) of repeat
      injection eyes. CONCLUSIONS: Elevated IOP after IVTA is common and patients
      should be monitored beyond 6 months post-injection. Patients with a baseline IOP
      more than 16 mm Hg or receiving a second injection should be carefully monitored
      for an elevated IOP.

PMID- 16597665
TI  - Microkeratome assisted deep lamellar keratoprosthesis.
AB  - AIMS: To establish a keratoprosthesis (Kpro) surgical technique that maintains an
      intact superficial corneal layer. METHODS: A manual microkeratome (Moria LSK-1)
      was used to create a 130 mum flap of approximately 10 mm diameter in the right
      eye of Japanese white rabbits. The stoma beneath the flap area was dissected
      before the removal of a 5.0 mm stromal disc. A 5.0 mm collagen I immobilised
      poly(vinyl alcohol) (COL-PVA) disc was placed on the exposed posterior stroma
      close to Descemet's membrane. The flap was repositioned and fixed using 10-0
      nylon sutures, which were removed 2 days following surgery. The corneas were
      followed clinically by slit lamp microscopy and photographs. Rabbits were
      sacrificed after 6 months, and the transplanted corneas were examined
      histologically by haematoxylin and eosin staining and immunohistochemistry
      against vimentin and alpha-smooth muscle actin (alpha-SMA). RESULTS: The
      transplanted COL-PVA discs remained transparent throughout the study, with no
      complications related to the flap or overlying epithelium. The interface between
      COL-PVA and Descemet's membrane remained clear without signs of opacification
      caused by scarring or cellular deposition. Pathology revealed the intact COL-PVA
      polymer in the posterior stroma, with minimal cellular infiltration along the
      anterior and posterior interfaces. Immunohistology shows vimentin and alpha-SMA
      staining at levels comparable to lamellar keratoplasty control. CONCLUSIONS:
      Microkeratome assisted deep lamellar keratoprosthesis may be a safe technique for
      the transplantation of artificial hydrogels for therapeutic purposes.

PMID- 16597666
TI  - Safety enhanced photodynamic therapy with half dose verteporfin for chronic
      central serous chorioretinopathy: a short term pilot study.
AB  - AIM: To evaluate short term safety of an enhanced photodynamic therapy (PDT)
      protocol with half dose verteporfin for treating chronic central serous
      chorioretinopathy (CSC). METHODS: 20 eyes of 18 patients with symptomatic chronic
      CSC underwent PDT using 3 mg/m2 verteporfin. Verteporfin was infused over 8
      minutes followed by indocyanine green angiography guided laser application 2
      minutes later. Serial optical coherence tomography (OCT) and multifocal
      electroretinography (mfERG) recordings were performed before PDT, at 4 days, 2
      weeks, and 1 month after PDT. The best corrected visual acuity (BCVA), OCT
      central retinal thickness, and mean mfERG response amplitudes and peak latencies
      were compared longitudinally. Subgroup analysis was further performed for eyes
      with or without pigment epithelial detachment (PED). RESULTS: At 1 month after
      PDT, the median BCVA improved from 20/40 to 20/30 (p = 0.001). The mean central
      retinal thickness also reduced from 276 microm to 158 microm (p < 0.001) and 17
      (85%) eyes had complete resolution of serous retinal detachment and/or PED. MfERG
      showed no significant changes in the mean N1 and P1 response amplitude and
      latency for all eyes. Subgroup analysis demonstrated that eyes without PED had a
      significant increase in the mean central mfERG P1 response amplitude with
      reduction in P1 peak latency at 1 month post-PDT. For eyes with PED, transient
      reduction in the mean central P1 response amplitude was observed at 4 days post
      PDT. CONCLUSIONS: The modified safety enhanced PDT protocol with half dose
      verteporfin appeared to be a beneficial treatment option for patients with
      chronic CSC, especially in eyes without serous PED. Further controlled study is
      warranted to demonstrate the long term safety and efficacy of this treatment
      option.

PMID- 16597667
TI  - Diagnosis and treatment of cytomegalovirus iridocyclitis without retinal
      necrosis.
AB  - AIM: To describe the diagnostic and therapeutic management of cytomegalovirus
      (CMV) anterior uveitis unassociated with retinal necrosis in immunocompetent
      patients. METHODS: Patients referred between 2001 and 2003 for management of
      unilateral, chronic, recurrent uveitis associated with secondary glaucoma
      underwent extensive investigation including laboratory tests for herpes virus
      infections. Specific antiviral treatment was initiated in all cases and the level
      of ocular inflammation was evaluated during the follow up. RESULTS: Five
      patients, three men and two women, were included. Median age was 50 years old
      (range 30-80 years). Anterior unilateral uveitis without iris atrophy was
      observed in all cases. Uveitis was chronic in three cases and recurrent in two
      cases. Glaucoma was observed in all patients with a median intraocular pressure
      of 30 mm Hg (range 22-43 mm Hg). Five patients responded initially to specific
      anti-CMV therapy. Even though glaucoma surgery was necessary in two cases, both
      ocular inflammation and glaucoma were controlled in all cases. Relapses occurred
      in three cases after cessation of therapy, requiring prolonged maintenance
      therapy with valganciclovir. CONCLUSIONS: CMV infection and specific antiviral
      therapy should be considered in all cases of relapsing or chronic iridocyclitis
      and secondary glaucoma. Maintenance regimens of valganciclovir may be necessary
      to prevent further relapses.

PMID- 16597669
TI  - Wanted--new methodologies for health service research. Is complexity theory the
      answer?
AB  - Despite a recognition that health service research has failed to make its full
      contribution to health service improvement, the fact that evidence is not widely
      accommodated into practice is seen as a failure of communication rather than the
      inappropriate application of a particular form of investigation. Dominant
      theoretical frameworks still retain the fundamental idea that order needs to be
      somehow created by external forces and that organizational issues will inevitably
      yield to more collection of data and the application of increasingly
      sophisticated analytical techniques. This paper explores alternative perspectives
      and methodological opportunities that arise from viewing health service as a
      complex non-linear system. This approach may offer new research insights that
      more accurately reflect underlying mechanisms and may help to explain the
      limitations of current analytical techniques.

PMID- 16597668
TI  - Does smoking influence the type of age related macular degeneration causing
      visual impairment?
AB  - AIMS: To assess the influence of smoking on the type of age related macular
      degeneration (AMD) lesion causing visual impairment in a large cohort of patients
      with AMD at a tertiary referral UK centre. METHODS: Prospective, observational,
      cross sectional study to analyse smoking data on 711 subjects, of western
      European origin, in relation to the type of AMD lesion present. Colour fundus
      photographs were graded according to a modified version of the international
      classification. Multiple logistic regression analysis was performed, adjusting
      for age and sex using the statistical package SPSS ver 9.0 for Windows. chi(2)
      tests were also used to assess pack year and ex-smoker data. RESULTS: 578
      subjects were graded with neovascular AMD and 133 with non-neovascular AMD. There
      was no statistically significant association found between smoking status or
      increasing number of pack years and type of AMD lesion. The odds of "current
      smokers" compared to "non-smokers" developing neovascular rather than non
      neovascular AMD when adjusted for age and sex was 1.88 (95% CI: 0.91 to 3.89; p =
      0.09). CONCLUSIONS: Smoking is known to be a risk factor for AMD and this study
      suggests that smokers are at no more risk of developing neovascular than atrophic
      lesions.

PMID- 16597670
TI  - Parametric survival models for interval-censored data with time-dependent
      covariates.
AB  - We present a parametric family of regression models for interval-censored event
      time (survival) data that accomodates both fixed (e.g. baseline) and time
      dependent covariates. The model employs a three-parameter family of survival
      distributions that includes the Weibull, negative binomial, and log-logistic
      distributions as special cases, and can be applied to data with left, right,
      interval, or non-censored event times. Standard methods, such as Newton-Raphson,
      can be employed to estimate the model and the resulting estimates have an
      asymptotically normal distribution about the true values with a covariance matrix
      that is consistently estimated by the information function. The deviance function
      is described to assess model fit and a robust sandwich estimate of the covariance
      may also be employed to provide asymptotically robust inferences when the model
      assumptions do not apply. Spline functions may also be employed to allow for non
      linear covariates. The model is applied to data from a long-term study of type 1
      diabetes to describe the effects of longitudinal measures of glycemia (HbA1c)
      over time (the time-dependent covariate) on the risk of progression of diabetic
      retinopathy (eye disease), an interval-censored event-time outcome.

PMID- 16597671
TI  - The logistic transform for bounded outcome scores.
AB  - The logistic transformation, originally suggested by Johnson (1949), is applied
      to analyze responses that are restricted to a finite interval (e.g. (0,1)), so
      called bounded outcome scores. Bounded outcome scores often have a non-standard
      distribution, e.g. J- or U-shaped, precluding classical parametric statistical
      approaches for analysis. Applying the logistic transformation on a normally
      distributed random variable, gives rise to a logit-normal (LN) distribution. This
      distribution can take a variety of shapes on (0,1). Further, the model can be
      extended to correct for (baseline) covariates. Therefore, the method could be
      useful for comparative clinical trials. Bounded outcomes can be found in many
      research areas, e.g. drug compliance research, quality-of-life studies, and pain
      (and pain relief) studies using visual analog scores, but all these scores can
      attain the boundary values 0 or 1. A natural extension of the above approach is
      therefore to assume a latent score on 0,1) having a LN distribution. Two cases
      are considered: (a) the bounded outcome score is a proportion where the true
      probabilities have a LN distribution on (0,1) and (b) the bounded outcome score
      on [0,1] is a coarsened version of a latent score with a LN distribution on
      (0,1). We also allow the variance (on the transformed scale) to depend on
      treatment. The usefulness of our approach for comparative clinical trials will be
      assessed in this paper. It turns out to be important to distinguish the case of
      equal and unequal variances. For a bounded outcome score of the second type and
      with equal variances, our approach comes close to ordinal probit (OP) regression.
      However, ignoring the inequality of variances can lead to highly biased parameter
      estimates. A simulation study compares the performance of our approach with the
      two-sample Wilcoxon test and with OP regression. Finally, the different methods
      are illustrated on two data sets.

PMID- 16597673
TI  - Why Escherichia coli alpha-hemolysin induces calcium oscillations in mammalian
      cells--the pore is on its own.
AB  - Escherichia coli alpha-hemolysin (HlyA), archetype of a bacterial pore-forming
      toxin, has been reported to deregulate physiological Ca2+ channels, thus inducing
      periodic low-frequency Ca2+ oscillations that trigger transcriptional processes
      in mammalian cells. The present study was undertaken to delineate the mechanisms
      underlying the Ca2+ oscillations. Patch-clamp experiments were combined with
      single cell measurements of intracellular Ca2+ and with flowcytometric analyses.
      Application of HlyA at subcytocidal concentrations provoked Ca2+ oscillations in
      human renal and endothelial cells. However, contrary to the previous report, the
      phenomenon could not be inhibited by the Ca2+ channel blocker nifedipine and Ca2+
      oscillations showed no constant periodicity at all. Ca2+ oscillations were
      dependent on the pore-forming activity of HlyA: application of a nonhemolytic but
      bindable toxin had no effect. Washout experiments revealed that Ca2+ oscillations
      could not be maintained in the absence of toxin in the medium. Analogously,
      propidium iodide flux into cells occurred in the presence of HlyA, but cells
      rapidly became impermeable toward the dye after toxin washout, indicating
      resealing or removal of the membrane lesions. Finally, patch-clamp experiments
      revealed temporal congruence between pore formation and Ca2+ influx. We conclude
      that the nonperiodic Ca2+ oscillations induced by HlyA are not due to
      deregulation of physiological Ca2+ channels but derive from pulsed influxes of
      Ca2+ as a consequence of formation and rapid closure of HlyA pores in mammalian
      cell membranes.

PMID- 16597674
TI  - Cellular and molecular mechanisms of tissue protection by lipophilic calcium
      channel blockers.
AB  - Long-acting third-generation dihydropyridine calcium channel blockers (CCBs)
      improve endothelial dysfunction and prevent cardiovascular events in humans, but
      their cellular and molecular mechanisms of tissue protection are not elucidated
      in detail. We assessed organ (renal) protection by the highly lipophilic CCB
      lercanidipine in a double-transgenic rat (dTGR) model with overexpression of
      human renin and angiotensinogen genes. We randomly treated dTGR with
      lercanidipine (2.5 mg/kg/day; n=20) or vehicle (n=20) for 3 wk. Furthermore, we
      explored the influence of lercanidipine on protein kinase C (PKC) signaling in
      vivo and in vitro using endothelial and vascular smooth muscle cell cultures.
      Cumulative mortality was 60% in untreated dTGR, whereas none of the lercanidipine
      treated animals died (P<0.001). We found significantly less albuminuria and
      improved renal function in lercanidipine-treated dTGR (both P<0.05).
      Lercanidipine treatment also significantly (P<0.05) reduced blood levels of the
      endogenous NOS inhibitor asymmetric dimethylarginine. On histological
      examination, we observed significantly less tissue inflammation and fibrosis in
      lercanidipine-treated animals (both P<0.05). Lercanidipine significantly
      inhibited angiotensin (ANG) I-mediated PKC-alpha and -delta activation in vivo
      and in vitro, partly due to reduced intracellular calcium flux. As a result,
      lercanidipine improved endothelial cell permeability in vitro. Lercanidipine
      prevents tissue injury and improves survival in a model of progressive organ
      damage. These effects may result, at least in part, from inhibition of tissue
      inflammation as well as improved NO bioavailability. Modulation of PKC activity
      may be an important underlying intracellular mechanism.

PMID- 16597675
TI  - Switchable electro-optic diffractive lens with high efficiency for ophthalmic
      applications.
AB  - Presbyopia is an age-related loss of accommodation of the human eye that
      manifests itself as inability to shift focus from distant to near objects.
      Assuming no refractive error, presbyopes have clear vision of distant objects;
      they require reading glasses for viewing near objects. Area-divided bifocal
      lenses are one example of a treatment for this problem. However, the field of
      view is limited in such eyeglasses, requiring the user to gaze down to accomplish
      near-vision tasks and in some cases causing dizziness and discomfort. Here, we
      report on previously undescribed switchable, flat, liquid-crystal diffractive
      lenses that can adaptively change their focusing power. The operation of these
      spectacle lenses is based on electrical control of the refractive index of a 5
      mum-thick layer of nematic liquid crystal using a circular array of
      photolithographically defined transparent electrodes. It operates with high
      transmission, low voltage (<2 Vrms), fast response (<1 sec), diffraction
      efficiency > 90%, small aberrations, and a power-failure-safe configuration.
      These results represent significant advance in state-of-the-art liquid-crystal
      diffractive lenses for vision care and other applications. They have the
      potential of revolutionizing the field of presbyopia correction when combined
      with automatic adjustable focusing power.

PMID- 16597676
TI  - Phenolic lipid synthesis by type III polyketide synthases is essential for cyst
      formation in Azotobacter vinelandii.
AB  - Cysts of Azotobacter vinelandii are resting cells that are surrounded by a
      protective coat, conferring resistance to various chemical and physical agents.
      The major chemical components of the cyst coat are alkylresorcinols, which are
      amphiphilic molecules possessing an aromatic ring with a long aliphatic carbon
      chain. Although alkylresorcinols are widely distributed in bacteria, fungi,
      plants, and animals, no enzyme systems for their biosynthesis are known. We
      report here an ars operon in A. vinelandii that is responsible for the
      biosynthesis of the alkylresorcinols in the cysts. The ars operon consisted of
      four genes, two of which encoded a type III polyketide synthase, ArsB and ArsC.
      In vitro experiments revealed that ArsB and ArsC, sharing 71% amino acid sequence
      identity, were an alkylresorcinol synthase and an alkylpyrone synthase,
      respectively, indicating that ArsB and ArsC are not isozymes but enzymatically
      distinct polyketide synthases. In addition, ArsB and ArsC accepted several acyl
      CoAs with various lengths of the side chain as a starter substrate and gave
      corresponding alkylresorcinols and alkylpyrones, respectively, which suggests
      that the mode of the ring folding is uninfluenced by the structure of the starter
      substrates. The importance of the alkylresorcinols for encystment was confirmed
      by gene inactivation experiments; the lack of alkylresorcinols synthesis caused
      by ars mutations resulted in the formation of severely impaired cysts, as
      observed by electron microscopy.

PMID- 16597677
TI  - Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of
      individuals in families with hereditary leiomyomatosis and renal cell cancer.
AB  - BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is the
      autosomal dominant heritable syndrome with predisposition to development of renal
      cell carcinoma and smooth muscle tumours of the skin and uterus. OBJECTIVE: To
      measure the fumarate hydratase (FH) enzyme activity in lymphoblastoid cell lines
      and fibroblast cell lines of individuals with HLRCC and other familial renal
      cancer syndromes. METHODS: FH enzyme activity was determined in the whole cell,
      cytosolic, and mitochondrial fractions in 50 lymphoblastoid and 16 fibroblast
      cell lines including cell lines from individuals with HLRCC with 16 different
      mutations. RESULTS: Lymphoblastoid cell lines (n = 20) and fibroblast cell lines
      (n = 11) from individuals with HLRCC had lower FH enzyme activity than cells from
      normal controls (p<0.05). The enzyme activity in lymphoblastoid cell lines from
      three individuals with mutations in R190 was not significantly different from
      individuals with other missense mutations. The cytosolic and mitochondrial FH
      activity of cell lines from individuals with HLRCC was reduced compared with
      those from control cell lines (p<0.05). There was no significant difference in
      enzyme activity between control cell lines (n = 4) and cell lines from affected
      individuals with other hereditary renal cancer syndromes (n = 22). CONCLUSIONS:
      FH enzyme activity testing provides a useful diagnostic method for confirmation
      of clinical diagnosis and screening of at-risk family members.

PMID- 16597679
TI  - Distinct and separable roles of the complement system in factor H-deficient bone
      marrow chimeric mice with immune complex disease.
AB  - Plasma complement factor H (Cfh) is a potent complement regulator, whereas Cfh on
      the surface of rodent platelets is responsible for immune complex processing. For
      dissection between the two, bone marrow chimeras between Cfh-deficient (Cfh(-/-))
      and wild-type C57BL/6 mice were created. Platelet Cfh protein was tracked with
      the Cfh status of the bone marrow donor, indicating that platelet Cfh is of
      intrinsic origin. In an active model of immune complex disease, Cfh(-/-) mice
      that were reconstituted with wild-type bone marrow had levels of platelet
      associated immune complexes comparable to those of wild-type mice and were
      protected against the excessive glomerular deposition of immune complexes seen in
      Cfh(-/-) mice, yet these mice still developed glomerular inflammation. In
      contrast, wild-type mice with Cfh(-/-) bone marrow had reduced platelet
      associated immune complexes and extensive glomerular deposition of complement
      activating immune complexes, but they did not develop glomerular pathology. The
      large quantities of glomerular C3 in wild-type mice with Cfh(-/-) bone marrow
      were in the form of iC3b and C3dg, whereas active C3b remained in Cfh(-/-)
      recipients of wild-type bone marrow. These data show that plasma Cfh limits
      complement activation in the circulation and other accessible sites such as the
      glomerulus, whereas platelet Cfh is responsible for immune complex processing.

PMID- 16597678
TI  - High incidence of SHOX anomalies in individuals with short stature.
AB  - OBJECTIVE: To study the SHOX gene and the PAR1 region in individuals with short
      stature. METHODS: The study involved 56 cases of dyschondrosteosis and 84 cases
      of idiopathic short stature (ISS). The study was designed to determine the
      following: the prevalence of SHOX anomalies in ISS; the frequency of Madelung
      deformity in individuals with SHOX anomalies; and the value of a family history
      of short stature in deciding whether to test for the SHOX gene. RESULTS: 54 SHOX
      anomalies were observed, including 42 (68%) in the dyschondrosteosis group and 12
      (15%) in the ISS group. The high frequency of SHOX anomalies in the ISS group can
      be explained by the large proportion of boys in this group, reflecting the
      difficulty in diagnosing dyschondrosteosis in young boys. Clinical evidence of
      Madelung deformity in six parents of ISS individuals emphasised the importance of
      family evaluation. Among the 54 SHOX anomalies, 33 PAR1 deletions were identified
      encompassing the SHOX gene (62%), one partial intragenic deletion (2%), nine
      deletions located downstream of the SHOX gene (16%), and 11 point mutations
      (20%). CONCLUSIONS: These data emphasise the value of using microsatellite
      markers located within and downstream of the SHOX gene.

PMID- 16597680
TI  - Relaxin improves renal function and histology in aging Munich Wistar rats.
AB  - Administration of recombinant human relaxin (rhRLX) to conscious, chronically
      instrumented rats increases GFR and effective renal plasma flow (ERPF) and
      decreases effective renal vascular resistance (ERVR) with no significant change
      in mean arterial pressure. The Munich Wistar albino rat shows progressive chronic
      nephrosis with age and therefore was used to determine the functional and
      histologic consequences of rhRLX on matrix remodeling in the kidney of older
      rats. RLX-infused rats showed increased GFR and ERPF with decreased ERVR.
      Furthermore, in a double-blinded examination, the renal histology showed a
      significant decrease in glomerular and tubular collagen deposition in the rhRLX
      infused aged rats. During short-term rhRLX administration (24 h), gelatinase
      activity was found to be essential for renal vasodilation and hyperfiltration.
      Surprisingly, after 20 d, improved renal function was insensitive to the
      inhibition of gelatinase activity, suggesting that collagen degradation in these
      rats had permanently altered the matrix of the renal vasculature. In conclusion,
      long-term administration of rhRLX improves renal function and ameliorates renal
      pathology in an aging rat model. The biphasic action of rhRLX on the kidney
      indicates that, acutely, the vessels dilate, causing increased filtration and
      renal blood flow with decreased vascular resistance as a result of upregulation
      of gelatinase activity. Subsequently, the renal vessels undergo alteration in
      supporting matrix, showing increased blood supply even in the face of acute
      matrix metalloproteinase inhibition, most likely as a result of the inhibitory
      properties of RLX on collagen production or increased collagen breakdown.

PMID- 16597681
TI  - Urine composition in type 2 diabetes: predisposition to uric acid
      nephrolithiasis.
AB  - Type 2 diabetes is a risk factor for nephrolithiasis in general and has been
      associated with uric acid stones in particular. The purpose of this study was to
      identify the metabolic features that place patients with type 2 diabetes at
      increased risk for uric acid nephrolithiasis. Three groups of individuals were
      recruited for this outpatient study: patients who have type 2 diabetes and are
      not stone formers (n = 24), patients who do not have diabetes and are uric acid
      stone formers (UASF; n = 8), and normal volunteers (NV; n = 59). Participants
      provided a fasting blood sample and a single 24-h urine collection for stone risk
      analysis. Twenty-four-hour urine volume and total uric acid did not differ among
      the three groups. Patients with type 2 diabetes and UASF had lower 24-h urine pH
      than NV. Urine pH inversely correlated with both body weight and 24-h urine
      sulfate in all groups. Urine pH remained significantly lower in patients with
      type 2 diabetes and UASF than NV after adjustment for weight and urine sulfate (P
      < 0.01). For a given urine sulfate, urine net acid excretion tended to be higher
      in patients with type 2 diabetes versus NV. With increasing urine sulfate, NV and
      patients with type 2 diabetes had a similar rise in urine ammonium, whereas in
      UASF, ammonium excretion remained unchanged. The main risk factor for uric acid
      nephrolithiasis in patients with type 2 diabetes is a low urine pH. Higher body
      mass and increased acid intake can contribute to but cannot entirely account for
      the lower urine pH in patients with type 2 diabetes.

PMID- 16597682
TI  - Increasing body mass index and obesity in the incident ESRD population.
AB  - An increase in obesity prevalence among patients who initiate dialysis may
      influence the growth of the total ESRD population as a result of improved
      survival and decreased likelihood for transplantation. Temporal trends in mean
      body mass index (BMI) and obesity prevalence were examined among incident
      patients with ESRD by year of dialysis initiation between 1995 and 2002, and
      these trends were compared with those in the US population during this same
      period. Among incident dialysis patients, BMI was calculated with the height and
      estimated dry weight collected from the Centers for Medicare and Medicaid
      Services End-Stage Renal Disease Medical Evidence Form. In the US population,
      self-reported height and weight were used. Prevalence of total obesity and
      obesity stage > or =2 were defined as a BMI > or =30 and > or =35 kg/m(2),
      respectively. Among incident patients with ESRD, mean BMI increased from 25.7 to
      27.5 kg/m(2), and total obesity and obesity stage > or =2 increased by 33 and
      63%, respectively, among incident patients with ESRD (P < 0.0001 for obesity
      trends). BMI slope was approximately two-fold higher in the incident ESRD
      population compared with the US population for all age groups. However, temporal
      increases in obesity prevalence were similar between the two populations. As a
      result of the survival advantage associated with obesity and decreased likelihood
      for transplantation, these trends most likely will influence the total number of
      patients who receive dialysis in the next decade.

PMID- 16597683
TI  - Left ventricular systolic function monitoring in asymptomatic dialysis patients:
      a prospective cohort study.
AB  - Although it is well established that compromised systolic function predicts
      cardiovascular (CV) complications in symptomatic and asymptomatic patients with
      ESRD, it still is unknown whether repeated echocardiographic measurements of
      systolic function in asymptomatic patients with ESRD is useful for monitoring the
      evolution of cardiomyopathy in these patients. The prognostic value for CV events
      of changes in systolic function, as measured by midwall fractional shortening
      (mwFS) in a cohort of 191 dialysis patients, was tested. Echocardiography was
      performed twice, 17 +/- 2 mo apart. Changes in mwFS (ch-mwFS) that occurred
      between the second and the first echocardiographic studies then were used to
      predict CV events during the ensuing 27 +/- 13 mo. After the second
      echocardiographic study, 85 patients had incident CV events. In a Kaplan-Meier
      analysis, there was a graded increase in the risk for fatal and nonfatal CV
      events across ch-mwFS quartiles (P = 0.005). On multivariate Cox regression
      analysis, ch-mwFS maintained an independent association with CV outcomes. In this
      analysis, the risk for CV events was 51% lower in patients who manifested an
      increase in mwFS (hazard ratio 0.49; 95% confidence interval 0.27 to 0.88; P =
      0.02) than in those who had a decrease in mwFS. Changes in mwFS have an
      independent prognostic value for CV events, and periodic echocardiographic
      studies of systolic function are useful for monitoring asymptomatic dialysis
      patients.

PMID- 16597684
TI  - Antioxidant ceruloplasmin is expressed by glomerular parietal epithelial cells
      and secreted into urine in association with glomerular aging and high-calorie
      diet.
AB  - Biologic aging is accelerated by high-calorie intake, increased free radical
      production, and oxidation of key biomolecules. Fischer 344 rats that are
      maintained on an ad libitum diet develop oxidant injury and age-associated
      glomerulosclerosis by 24 mo. Calorie restriction prevents both oxidant injury and
      glomerulosclerosis. Ceruloplasmin (Cp) is a copper-containing ferroxidase that
      functions as an antioxidant in part by oxidizing toxic ferrous iron to nontoxic
      ferric iron. Glomerular Cp mRNA and protein expression were measured in ad
      libitum-fed and calorie-restricted rats at ages 2, 6, 17, and 24 mo. In ad
      libitum-fed rats, Cp mRNA expression increased six-fold (P < 0.01) and protein
      expression increased five-fold (P = 0.01) between 2 and 24 mo of age. In calorie
      restricted rats, Cp mRNA expression increased three-fold (P < 0.01) and protein
      expression increased 1.6-fold (NS) between 2 and 24 mo of age. Both the cell
      associated alternately spliced variant and secreted variants of Cp were
      expressed. Immunofluorescent analysis showed that Cp was expressed by the
      parietal epithelial cells that line the inner aspect of Bowman's capsule in the
      glomerulus. Cp also was present in urine, particularly of old ad libitum-fed rats
      with high tissue Cp expression. Cp expression by Bowman's capsule epithelial
      cells therefore occurred in direct proportion to known levels of oxidant activity
      (older age and high-calorie diet) and is secreted into the urine. It is suggested
      that Cp expression at this site may be part of the repertoire of the glomerular
      parietal epithelial cell to protect the glomerular podocytes and the downstream
      nephron from toxic effects of filtered molecules, including ferrous iron.

PMID- 16597685
TI  - Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for
      vitamin D.
AB  - The regulation of the phosphaturic factor fibroblast growth factor 23 (FGF23) is
      not well understood. It was found that administration of 1,25-dihydroxyvitamin
      D(3) (1,25[OH](2)D(3)) to mice rapidly increased serum FGF23 concentrations from
      a basal level of 90.6 +/- 8.1 to 213.8 +/- 14.6 pg/ml at 8 h (mean +/- SEM; P <
      0.01) and resulted in a four-fold increase in FGF23 transcripts in bone, the
      predominate site of FGF23 expression. In the Hyp-mouse homologue of X-linked
      hypophosphatemic rickets, administration of 1,25(OH)(2)D(3) further increased
      circulating FGF23 levels. In Gcm2 null mice, low 1,25(OH)(2)D(3) levels were
      associated with a three-fold reduction in FGF23 levels that were increased by
      administration of 1,25(OH)(2)D(3). In osteoblast cell cultures, 1,25(OH)(2)D(3)
      but not calcium, phosphate, or parathyroid hormone stimulated FGF23 mRNA levels
      and resulted in a dose-dependent increase in FGF23 promoter activity.
      Overexpression of a dominant negative vitamin D receptor inhibited
      1,25(OH)(2)D(3) stimulation of FGF23 promoter activity, and mutagenesis of the
      FGF23 promoter identified a vitamin D-responsive element (-1180 GGAACTcagTAACCT 
      1156) that is responsible for the vitamin D effects. These data suggest that
      1,25(OH)(2)D(3) is an important regulator of FGF23 production by osteoblasts in
      bone. The physiologic role of FGF23 may be to act as a counterregulatory
      phosphaturic hormone to maintain phosphate homeostasis in response to vitamin D.

PMID- 16597686
TI  - Influence of acute renal failure on coronary vasoregulation in dogs.
AB  - Impaired renal function is associated with an increased risk for cardiovascular
      events and death, but the pathophysiology is poorly defined. The hypothesis that
      coronary blood flow regulation and distribution of ventricular blood flow could
      be compromised during acute renal failure (ARF) was tested. In two separate
      groups (n = 14 each) of dogs with ARF, (1) coronary autoregulation (pressure-flow
      relations), vascular reserve (reactive hyperemia), and myocardial blood flow
      distribution (microspheres) and (2) coronary vessel responses to intracoronary
      infusion of select endothelium-dependent and -independent vasodilators were
      evaluated. In addition, coronary pressure-flow relations and vascular reserve
      after inhibition of nitric oxide and prostaglandin release were evaluated. Under
      resting conditions, myocardial oxygen consumption increased in dogs with ARF
      compared with no renal failure (NRF; 11.8 +/- 9.2 versus 5.0 +/- 1.5 ml O(2)/min
      per 100 g; P = 0.01), and the autoregulatory break point of the coronary pressure
      flow relation was shifted to higher diastolic coronary pressures (60 +/- 17
      versus 52 +/- 8 mmHg in NRF; P = 0.003); the latter was shifted further rightward
      after inhibition of both nitric oxide and prostaglandin release. The
      endocardial/epicardial blood flow ratio was comparable for both groups,
      suggesting preserved ventricular distribution of blood flow. In dogs with ARF,
      coronary vascular conductance also was reduced (P = 0.001 versus NRF), but
      coronary zero-flow pressure was unchanged. Vessel reactivity to each endothelium
      dependent/independent compound also was blunted significantly. In conclusion,
      under resting conditions, coronary vascular tone, reserve, and vessel reactivity
      are markedly diminished with ARF, suggesting impaired vascular function.
      Consequently, during ARF, small increases in myocardial oxygen demand would
      induce subendocardial ischemia as a result of a limited capacity to increase
      oxygen supply and thereby contribute to higher risk for adverse coronary events
      and mortality.

PMID- 16597687
TI  - Heme oxygenase-1 protects rat kidney from ureteral obstruction via an
      antiapoptotic pathway.
AB  - This study examined the functional significance of heme oxygenase-1 (HO-1)
      expression on renal injury induced by ureteral obstruction in the rat kidney.
      Male Sprague-Dawley rats were divided into three groups, after which unilateral
      ureteral obstruction (UUO) was performed: untreated (group 1), treated with 30
      mg/kg body wt hemin (group 2), and treated with 50 microg/kg body wt zinc (alpha)
      protoporphyrin eta (ZnPP) and 30 mg/kg hemin (group 3). After 7 and 14 d,
      histologic changes and the expression of HO-1, Bcl-2, Bad, TGF-beta, and cleaved
      caspase-3 were examined. Tubular lumens were dilated and epithelial cells were
      flattened on day 7 after UUO. Interstitial fibrosis and separation of the tubules
      were markedly increased on day 14. In contrast, the kidneys that were treated
      with hemin exhibited minimal interstitial fibrosis and flattening of epithelial
      cells on day 7 and fewer changes on day 14 than in the controls. However,
      treatment with ZnPP, an inhibitor of HO enzyme activity, eliminated the
      beneficial effect of hemin on interstitial fibrosis and tubular dilation.
      Increased HO-1 expression was associated with increased Bcl-2. In the ZnPP
      treated rats, Bcl-2 signals were decreased compared with the hemin group. The
      level of proapoptotic Bad was not changed in any group. The positive cells for
      cleaved caspase-3 were significantly increased in renal tubular epithelial cells
      and tubulointerstitial cells in the obstructed rats, and hemin treatment
      decreased the caspase-3 activation. This study demonstrates that upregulation of
      HO-1 provides protection against renal injury that follows UUO. This effect is
      dependent on modulation of the antiapoptotic pathway by HO-1 expression.

PMID- 16597688
TI  - Fever-like temperatures affect neutrophil NF-kappaB signaling, apoptosis, and
      ANCA-antigen expression.
AB  - The neutrophil is pivotal to ANCA vasculitis pathogenesis. Fever frequently
      complicates ANCA diseases. This study investigated the effects of short-term heat
      exposure on apoptosis in neutrophils that were treated with LPS, GM-CSF, IL-8,
      and dexamethasone. All compounds delayed apoptosis. Heat abrogated the apoptosis
      delaying effect of LPS without affecting constitutive apoptosis or delayed
      apoptosis by GM-CSF, IL-8, or dexamethasone. The heat effect was dose dependent
      over the 39 to 42 degrees C range. NF-kappaB but not extracellular signal
      regulated kinase, p38 mitogen-activated protein kinase (MAPK), or
      phosphatidylinositol 3-kinase/Akt controlled LPS-delayed apoptosis. Furthermore,
      LPS-induced IkappaBalpha degradation, DNA binding, and NF-kappaB-dependent gene
      transcription activation were abrogated by short-term heat. When core
      temperatures were raised to 40.5 degrees C for 30 min in mice, LPS-induced
      neutrophil NF-kappaB activation also was prevented. Short-term heat removed heat
      shock protein 90 from the IkappaB kinase complex, resulting in failure of LPS
      induced IkappaB kinase activation. Despite delayed apoptosis, ANCA antigen
      expression was increased in LPS-treated neutrophils. ANCA antigen increase was
      prevented by p38 MAPK inhibition and by heat exposure. Heat exposure did not
      inhibit LPS-induced p38 MAPK phosphorylation. Instead, apoptosis-mediated p38
      MAPK degradation was accelerated, thereby decreasing the p38 MAPK that was
      available for LPS-mediated ANCA antigen upregulation. These data suggest that
      fever-like temperatures modulate neutrophil behavior in this disease.

PMID- 16597689
TI  - High glucose blunts vascular endothelial growth factor response to hypoxia via
      the oxidative stress-regulated hypoxia-inducible factor/hypoxia-responsible
      element pathway.
AB  - Vascular endothelial growth factor (VEGF) is an important survival factor for
      endothelial cells in hypoxic environments. High glucose regulates certain aspects
      of VEGF expression in various cell types, including proximal tubular cells. Thus,
      ambient glucose levels may modulate the progression of chronic kidney disease,
      especially diabetic nephropathy. Immortalized rat proximal tubular cells (IRPTC)
      were cultured for 24 h under hypoxic conditions (1% O(2)), with or without high d
      glucose (25 mM), or with or without high l-glucose (25 mM). Controls included
      culture in normoxic conditions and normal d-glucose (5.5 mM). VEGF mRNA
      expression was assessed by real-time quantitative PCR, and VEGF protein in the
      supernatant was assessed by ELISA. Hypoxia increased VEGF expression. This
      response was significantly blunted by high d-glucose (1.98 +/- 0.11- versus 2.65
      +/- 0.27-fold increase for VEGF mRNA expression, 252.8 +/- 14.7 versus 324.0 +/-
      11.5 pg/10(5) cells for VEGF protein; P < 0.05 both) but not by high l-glucose.
      It is interesting that hydrogen peroxide also blunted this response, whereas
      alpha-tocopherol restored the VEGF response to hypoxia in the presence of high d
      glucose. For determination of involvement of the hypoxia-inducible factor
      (HIF)/hypoxia-responsible element (HRE) pathway, IRPTC that were stably
      transfected with HRE-luciferase were cultured under the previous conditions. High
      d-glucose also reduced luciferase activity under hypoxia, whereas alpha
      tocopherol restored activity. In vivo experiments using streptozotocin-induced
      diabetic rats confirmed that hyperglycemia blunted HIF-HRE pathway activation.
      Insulin treatment restored activation of the HIF-HRE pathway in streptozotocin
      induced diabetic rats. In conclusion, high glucose blunts VEGF response to
      hypoxia in IRPTC. This effect is mediated by the oxidative stress-regulated HIF
      HRE pathway.

PMID- 16597690
TI  - Uptake of chemically reactive, DNA-damaging sulfuric acid esters into renal cells
      by human organic anion transporters.
AB  - The procarcinogen 1-methylpyrene is activated by hepatic enzymes via 1
      hydroxymethylpyrene to 1-sulfooxymethylpyrene (1-SMP), a highly reactive and
      mutagenic metabolite. Previously, high levels of 1-SMP DNA adducts were observed
      in rat kidneys after intraperitoneal administration of 1-hydroxymethylpyrene or 1
      SMP. This study examined whether organic anion transporters (OAT) that are
      expressed at the basolateral membrane of proximal tubule cells are involved in
      uptake of SMP. Human epithelial kidney (HEK293) cells that stably express human
      OAT1 (hOAT1) and hOAT3 were used. Stable isomers of 1-SMP, (2-SMP and 4-SMP)
      competitively inhibited the uptake of characteristic substrates p-aminohippurate
      for hOAT1 and estrone sulfate for hOAT3. Both inhibitors exhibited high affinity
      for hOAT1 (K(i) = 4.4 microM for 2-SMP; K(i) = 5.1 microM for 4-SMP) as well as
      hOAT3 (K(i) = 1.9 microM for 2-SMP; K(i) = 2.1 microM for 4-SMP). The uptake rate
      of 4-SMP (at a concentration of 10 microM) by hOAT1- and hOAT3-expressing cells
      was 3.0 and 1.6 times higher, respectively, than in control cells. Uptake of the
      reactive isomer 1-SMP was investigated using as the end point the level of DNA
      adducts that were formed in the cells. After exposure to 1-SMP (10 microM), the
      DNA adduct level was 4.6 and 3.0 times higher in hOAT1- and hOAT3-expressing
      cells, respectively, than in control cells. The enhanced DNA adduct formation in
      hOAT-expressing cells was abolished in the presence of the OAT inhibitor
      probenecid. This study indicates that OAT can mediate the basolateral uptake of
      reactive sulfuric acid esters into proximal tubule cells and thereby participate
      in kidney cell damage by these compounds.

PMID- 16597691
TI  - Mammalian target of rapamycin pathway blockade slows progression of diabetic
      kidney disease in rats.
AB  - Recent data suggest that the phosphatidylinositol 3-kinase (PI3-K)/Akt/mammalian
      target of rapamycin (mTOR) pathway is important in diabetic nephropathy. The
      effect of mTOR blockade by sirolimus (SRL) in diabetic kidney disease in rats was
      investigated. Diabetes was induced by streptozotocin in male Sprague-Dawley rats.
      Sixteen weeks later, diabetic animals were divided into the following groups:
      diabetes (D; n = 8), diabetes + SRL at 1 mg/kg per d, SRL trough level 2.3 +/-
      0.25 ng/ml (D+SRL; n = 7); and diabetes + normoglycemia maintained by insulin
      implants (D+NG; n = 5). There was an age-matched nondiabetic group (ND; n = 6).
      All animals were followed for 4 wk. The D group showed glomerular hypertrophy
      (mean glomerular volume 5.0 +/- 0.4 in D versus 3.3 +/- 0.2 10(6) mu(3) in ND; P
      < 0.05) without renal hyperplasia (calculated by reverse transcription-PCR of
      proliferative cell nuclear antigen) and albuminuria (29 +/- 4 in D versus 1.4 +/-
      1.5 mg/24 h in ND; P < 0.05). Both D+NG and D+SRL groups had a significant
      reduction of albuminuria, although glomerular hypertrophy was still present. SRL
      treatment did not modify the number of infiltrating renal ED1(+) cells. Diabetic
      animals had greater expression of p-Akt and mTOR, unlike ND rats. NG and SRL
      treatment reduced p-Akt and normalized mTOR. It is interesting that D+SRL was
      associated with a significant reduction of renal TGF-beta1 and glomerular
      connective tissue growth factor. SRL treatment reduced glomerular alpha-smooth
      muscle actin overexpression and reduced significantly the mesangial matrix
      accumulation that is characteristic of diabetic nephropathy. In conclusion, mTOR
      blockade by low-dose SRL has a beneficial effect in diabetic kidney disease,
      suggesting that the mTOR pathway has an important pathogenic role in diabetic
      nephropathy.

PMID- 16597692
TI  - Chromatid damage in human lymphocytes is not affected by 50 Hz electromagnetic
      fields.
AB  - Cultured human blood lymphocytes were exposed during the S/G(2) phases of the
      cell cycle to continuous extremely low frequency (50 Hz) electromagnetic fields
      of 0.23, 0.47 or 0.7 mT either alone or immediately after an acute exposure to
      1.0 Gy of gamma rays. The ionising radiation, as expected, induced chromosomal
      aberrations of the chromatid-type observed at the next metaphase. The field
      applied alone did not induce chromosomal damage nor did it modify the frequency
      of aberrations caused by the gamma rays.

PMID- 16597693
TI  - Comparative performance tests of the FLUKA-RQMD system and EPAX 2 previsions vs.
      experimental data.
AB  - This work describes the tests performed on the RQMD module (available in the
      FLUKA code), to support nucleus-nucleus interactions above 100 MeV u(-1). The
      RQMD-FLUKA system was used to simulate directly simple experimental set-ups to
      reproduce both secondary hadron production and residual nuclei distributions with
      ion beams ranging from 100 to 800 MeV u(-1). Recent measurements of residual
      nuclei distributions due to interaction of light ion beams on high-purity targets
      were used as reference for testing the RQMD-FLUKA prediction capability. Together
      with FLUKA, the EPAX 2 code was considered as a further reference in
      fragmentation cross sections. EPAX shows a general tendency to underestimate the
      experimental fragmentation cross sections for the considered projectile-target
      combinations. EPAX underestimations are generally close to 40%, whereas FLUKA
      predictions are within 20% on the average.

PMID- 16597694
TI  - Operational specifications of the laser illuminated track etch scattering
      dosemeter reader.
AB  - The personnel dosimetry operations team at the Los Alamos National Laboratory
      (LANL) has accepted the laser illuminated track etch scattering (LITES) dosemeter
      reader into its suite of radiation dose measurement instruments. The LITES
      instrument transmits coherent light from a He-Ne laser through the pertinent
      track etch foil and a photodiode measures the amount of light scattered by the
      etched tracks. A small beam stop blocks the main laser light, while a lens
      refocuses the scattered light into the photodiode. Three stepper motors in the
      current LITES system are used to position a carousel that holds 36 track etch
      dosemeters (TEDs). Preliminary work with the LITES system demonstrated the device
      had a linear response in counting foils subjected to exposures up to 50 mSv (5.0
      rem). The United States Department of Energy requires that the annual general
      employee dose not exceed 50 mSv (5.0 rem). On a regular basis, LANL uses the
      Autoscan-60 reader system (Thermo Electron Corp.) for counting track etch
      dosemeters. However, LANL uses a 15 h etch process for CR-39 dosemeters, and this
      produces more and larger track etch pits than the 6 h etch used by many
      institutions. Therefore, LANL only uses the Autoscan-60 for measuring neutron
      dose equivalent up to exposure levels of approximately 3 mSv (300 mrem). The
      LITES system has a measured lower limit of detection of approximately 0.6 mSv (60
      mrem), and it has a correlation coefficient of R (2) = 0.99 over an exposure
      range up to 500 mSv (50.0 rem). A series of blind studies were done using three
      methods: the Autoscan-60 system, manual counting by optical microscope and the
      LITES instrument. A collection of track etch dosemeters of unknown neutron dose
      equivalent (NDE) were analysed using the three methods, and the performance
      coefficient (PC) was calculated when the NDE became known. The Autoscan-60 and
      optical microscope methods had a combined PC = 0.171, and the LITES instrument
      had a PC = 0.194, where a PC less than or equal to 0.300 is considered
      satisfactory.

PMID- 16597695
TI  - Extremely high dose neutron dosimetry using CR-39 and atomic force microscopy.
AB  - Atomic force microscopy (AFM) has been applied to the analysis of CR-39 nuclear
      track detectors for high dose neutron dosimetry. As a feasible study to extract
      the neutron dose, we have employed a (239)Pu-Be neutron source with the
      traditional track density measurement of recoil proton etch pits from a high
      density polyethylene (CH(2)) radiator. After very short etching ( approximately 1
      microm), etch pit densities were measured as a function of neutron fluence
      (neutron dose) up to 1.4 x 10(10) cm(-2) (6.6 Sv). Neutron sensitivity was also
      measured to be 6.6 x 10(-4). Maximum measurable neutron dose was estimated to be
      approximately 200 Sv by measuring the fraction of the total image area occupied
      by the etch pits.

PMID- 16597696
TI  - ESR dating of an ancient goat tooth from Nuoro, Sardinia, Italy.
AB  - The dating of fossil teeth of an ancient goat (Nesogoral melonii) using the
      electron spin resonance (ESR) technique is reported. This animal was found in the
      fossiliferous site at Orosei (Nuoro, Sardinia, Italy) and was endemic in the
      region. Molar teeth were cleaned and enamel was completely removed from dentine.
      Enamel was irradiated with a 60Co gamma source and measured with an ESR
      spectrometer (X-band) to obtain the signal vs. dose curve and fitted with an
      exponential function. The archeological dose obtained by the fitting was 211 +/-
      34 Gy. Uranium and thorium concentrations were determined by neutron activation
      analysis. With the software ROSY the age estimates were 195 +/- 30 ky for early
      uptake, 247 +/- 40 ky for linear uptake and 243 +/- 40 ky for a combination of
      uptake processes.

PMID- 16597698
TI  - GUP1 of Saccharomyces cerevisiae encodes an O-acyltransferase involved in
      remodeling of the GPI anchor.
AB  - The anchors of mature glycosylphosphatidylinositol (GPI)-anchored proteins of
      Saccharomyces cerevisiae contain either ceramide or diacylglycerol with a C26:0
      fatty acid in the sn2 position. The primary GPI lipid added to newly synthesized
      proteins in the ER consists of diacylglycerol with conventional C16 and C18 fatty
      acids. Here we show that GUP1 is essential for the synthesis of the C26:0
      containing diacylglycerol anchors. Gup1p is an ER membrane protein with multiple
      membrane-spanning domains harboring a motif that is characteristic of membrane
      bound O-acyl-transferases (MBOAT). Gup1Delta cells make normal amounts of GPI
      proteins but most mature GPI anchors contain lyso-phosphatidylinositol, and
      others possess phosphatidylinositol with conventional C16 and C18 fatty acids.
      The incorporation of the normal ceramides into the anchors is also disturbed. As
      a consequence, the ER-to-Golgi transport of the GPI protein Gas1p is slow, and
      mature Gas1p is lost from the plasma membrane into the medium. Gup1Delta cells
      have fragile cell walls and a defect in bipolar bud site selection. GUP1 function
      depends on the active site histidine of the MBOAT motif. GUP1 is highly conserved
      among fungi and protozoa and the gup1Delta phenotype is partially corrected by
      GUP1 homologues of Aspergillus fumigatus and Trypanosoma cruzi.

PMID- 16597697
TI  - Caenorhabditis elegans kettin, a large immunoglobulin-like repeat protein, binds
      to filamentous actin and provides mechanical stability to the contractile
      apparatuses in body wall muscle.
AB  - Kettin is a large actin-binding protein with immunoglobulin-like (Ig) repeats,
      which is associated with the thin filaments in arthropod muscles. Here, we report
      identification and functional characterization of kettin in the nematode
      Caenorhabditis elegans. We found that one of the monoclonal antibodies that were
      raised against C. elegans muscle proteins specifically reacts with kettin (Ce
      kettin). We determined the entire cDNA sequence of Ce-kettin that encodes a
      protein of 472 kDa with 31 Ig repeats. Arthropod kettins are splice variants of
      much larger connectin/titin-related proteins. However, the gene for Ce-kettin is
      independent of other connectin/titin-related genes. Ce-kettin localizes to the
      thin filaments near the dense bodies in both striated and nonstriated muscles.
      The C-terminal four Ig repeats and the adjacent non-Ig region synergistically
      bind to actin filaments in vitro. RNA interference of Ce-kettin caused weak
      disorganization of the actin filaments in body wall muscle. This phenotype was
      suppressed by inhibiting muscle contraction by a myosin mutation, but it was
      enhanced by tetramisole-induced hypercontraction. Furthermore, Ce-kettin was
      involved in organizing the cytoplasmic portion of the dense bodies in cooperation
      with alpha-actinin. These results suggest that kettin is an important regulator
      of myofibrillar organization and provides mechanical stability to the myofibrils
      during contraction.

PMID- 16597699
TI  - MAP kinase pathway-dependent phosphorylation of the L1-CAM ankyrin binding site
      regulates neuronal growth.
AB  - The growth of neuronal processes depends critically on the function of adhesion
      proteins that link extracellular ligands to the cytoskeleton. The neuronal
      adhesion protein L1-CAM serves as a receptor for nerve growth-promoting proteins,
      a process that is inhibited by the interaction between L1-CAM and the
      cytoskeleton adaptor ankyrin. Using a novel reporter based on intramolecular
      bioluminescence resonance energy transfer, we have determined that the MAP kinase
      pathway regulates the phosphorylation of the FIGQY motif in the adhesion protein
      L1-CAM and its interaction with ankyrin B. MAP kinase pathway inhibitors block L1
      CAM-mediated neuronal growth. However, this blockade is partially rescued by
      inhibitors of L1-CAM-ankyrin binding. These results demonstrate that the MAP
      kinase pathway regulates L1-CAM-mediated nerve growth by modulating ankyrin
      binding, suggesting that nerve growth can be regulated at the level of individual
      receptors.

PMID- 16597700
TI  - In vivo dynamics of Rac-membrane interactions.
AB  - The small GTPase Rac cycles between the membrane and the cytosol as it is
      activated by nucleotide exchange factors (GEFs) and inactivated by GTPase
      activating proteins (GAPs). Solubility in the cytosol is conferred by binding of
      Rac to guanine-nucleotide dissociation inhibitors (GDIs). To analyze the in vivo
      dynamics of Rac, we developed a photobleaching method to measure the dissociation
      rate constant (k(off)) of membrane-bound GFP-Rac. We find that k(off) is 0.048 s(
      1) for wtRac and approximately 10-fold less (0.004 s(-1)) for G12VRac. Thus, the
      major route for dissociation is conversion of membrane-bound GTP-Rac to GDP-Rac;
      however, dissociation of GTP-Rac occurs at a detectable rate. Overexpression of
      the GEF Tiam1 unexpectedly decreased k(off) for wtRac, most likely by converting
      membrane-bound GDP-Rac back to GTP-Rac. Both overexpression and small hairpin RNA
      mediated suppression of RhoGDI strongly affected the amount of membrane-bound Rac
      but surprisingly had only slight effects on k(off). These results indicate that
      RhoGDI controls Rac function mainly through effects on activation and/or membrane
      association.

PMID- 16597701
TI  - Fibronectin rigidity response through Fyn and p130Cas recruitment to the leading
      edge.
AB  - Cell motility on extracellular matrices critically depends on matrix rigidity,
      which affects cell adhesion and formation of focal contacts. Receptor-like
      protein tyrosine phosphatase alpha (RPTPalpha) and the alphavbeta3 integrin form
      a rigidity-responsive complex at the leading edge. Here we show that the rigidity
      response through increased spreading and growth correlates with leading edge
      recruitment of Fyn, but not endogenous c-Src. Recruitment of Fyn requires the
      palmitoylation site near the N-terminus and addition of that site to c-Src
      enables it to support a rigidity response. In all cases, the rigidity response
      correlates with the recruitment of the Src family kinase to early adhesions. The
      stretch-activated substrate of Fyn and c-Src, p130Cas, is also required for a
      rigidity response and it is phosphorylated at the leading edge in a Fyn-dependent
      process. A possible mechanism for the fibronectin rigidity response involves
      force-dependent Fyn phosphorylation of p130Cas with rigidity-dependent
      displacement. With the greater displacement of Fyn from p130Cas on softer
      surfaces, there will be less phosphorylation. These studies emphasize the
      importance of force and nanometer-level movements in cell growth and function.

PMID- 16597702
TI  - Filopodia formation in the absence of functional WAVE- and Arp2/3-complexes.
AB  - Cell migration is initiated by plasma membrane protrusions, in the form of
      lamellipodia and filopodia. The latter rod-like projections may exert sensory
      functions and are found in organisms as distant in evolution as mammals and
      amoeba such as Dictyostelium discoideum. In mammals, lamellipodia protrusion
      downstream of the small GTPase Rac1 requires a multimeric protein assembly, the
      WAVE-complex, which activates Arp2/3-mediated actin filament nucleation and actin
      network assembly. A current model of filopodia formation postulates that these
      structures arise from a dendritic network of lamellipodial actin filaments by
      selective elongation and bundling. Here, we have analyzed filopodia formation in
      mammalian cells abrogated in expression of essential components of the
      lamellipodial actin polymerization machinery. Cells depleted of the WAVE-complex
      component Nck-associated protein 1 (Nap1), and, in consequence, of lamellipodia,
      exhibited normal filopodia protrusion. Likewise, the Arp2/3-complex, which is
      essential for lamellipodia protrusion, is dispensable for filopodia formation.
      Moreover, genetic disruption of nap1 or the WAVE-orthologue suppressor of cAMP
      receptor (scar) in Dictyostelium was also ineffective in preventing filopodia
      protrusion. These data suggest that the molecular mechanism of filopodia
      formation is conserved throughout evolution from Dictyostelium to mammals and
      show that lamellipodia and filopodia formation are functionally separable.

PMID- 16597704
TI  - Parental smoking and the risk of childhood leukemia.
AB  - Cigarette smoke has been linked to adult myeloid leukemia; however, the
      association between parental smoking and childhood leukemia remains unclear.
      Parental smoking and the risk of childhood leukemia were examined in the Northern
      California Childhood Leukemia Study, a case-control study, between 1995 and 2002.
      The present analysis included 327 acute childhood leukemia cases (281 acute
      lymphoblastic leukemia (ALL) and 46 acute myeloid leukemia (AML)) and 416
      controls matched on age, sex, maternal race, and Hispanic ethnicity. Maternal
      smoking was not associated with an increased risk of either ALL or AML. Paternal
      preconception smoking was significantly associated with an increased risk of AML
      (odds ratio = 3.84, 95% confidence interval: 1.04, 14.17); an increased risk for
      ALL was suggestive for paternal preconception smoking (odds ratio = 1.32, 95%
      confidence interval: 0.86, 2.04). Greater risks of ALL were observed compared
      with the risk associated with paternal preconception smoking alone, when paternal
      preconception smoking was combined with maternal postnatal smoking
      (p(interaction) = 0.004) or postnatal passive smoking exposure (p(interaction) =
      0.004). These results strongly suggest that exposure to paternal preconception
      smoking alone or in combination with postnatal passive smoking may be important
      in the risk of childhood leukemia.

PMID- 16597705
TI  - Nocturia and obesity: a population-based study in Finland.
AB  - The authors' aim in this study was to analyze the association of nocturia with
      overweight and obesity. In 2003-2004, a questionnaire was mailed to 6,000
      randomly selected Finns aged 18-79 years who were identified from the Finnish
      Population Register Centre. Information on nocturia was collected through
      questionnaires using the Danish Prostatic Symptom Score and the American
      Urological Association Symptom Index. Self-reported body weight and height were
      used to calculate body mass index (BMI; weight (kg)/height (m)2). Subjects were
      classified on the basis of BMI as nonoverweight (BMI<25), overweight (BMI 25-29.9
      kgm2), or obese (BMI>or=30). Of the 6,000 subjects, 62.4% participated. Among
      men, the age-standardized prevalence of nocturia, defined as at least one void
      per night, was 33.4% (95% confidence interval (CI): 28.5, 38.3) in the
      nonoverweight, 35.8% (95% CI: 31.4, 40.1) in the overweight, and 48.2% (95% CI:
      38.8, 57.6) in the obese. Among women, the corresponding figures were 37.2% (95%
      CI: 33.0, 41.5) in the nonoverweight, 48.3% (95% CI: 42.5, 54.2) in the
      overweight, and 53.6% (95% CI: 43.9, 63.2) in the obese. The associations
      remained similar when nocturia was defined as two or more voids per night. The
      age-standardized attributable fraction (population) of increased BMI for nocturia
      was 17.7% for men and 18.5% for women, corresponding to an 8.5% increase in the
      crude prevalence of nocturia in men and a 13.9% increase in women. The authors
      conclude that obesity is associated with increased nocturia, more strongly among
      women than among men.

PMID- 16597703
TI  - Cytoplasmic lipid droplets are sites of convergence of proteasomal and autophagic
      degradation of apolipoprotein B.
AB  - Lipid esters stored in cytoplasmic lipid droplets (CLDs) of hepatocytes are used
      to synthesize very low-density lipoproteins (VLDLs), into which apolipoprotein B
      (ApoB) is integrated cotranslationally. In the present study, by using Huh7
      cells, derived from human hepatoma and competent for VLDL secretion, we found
      that ApoB is highly concentrated around CLDs to make "ApoB-crescents." ApoB
      crescents were seen in <10% of Huh7 cells under normal conditions, but the ratio
      increased to nearly 50% after 12 h of proteasomal inhibition by N-acetyl-L
      leucinyl-L-leucinyl-L-norleucinal. Electron microscopy showed ApoB to be
      localized to a cluster of electron-lucent particles 50-100 nm in diameter
      adhering to CLDs. ApoB, proteasome subunits, and ubiquitinated proteins were
      detected in the CLD fraction, and this ApoB was ubiquitinated. Interestingly,
      proteasome inhibition also caused increases in autophagic vacuoles and ApoB in
      lysosomes. ApoB-crescents began to decrease after 12-24 h of proteasomal
      inhibition, but the decrease was blocked by an autophagy inhibitor, 3
      methyladenine. Inhibition of autophagy alone caused an increase in ApoB
      crescents. These observations indicate that both proteasomal and
      autophagy/lysosomal degradation of ApoB occur around CLDs and that the CLD
      surface functions as a unique platform for convergence of the two pathways.

PMID- 16597706
TI  - Associations of serum carotenoid concentrations with the development of diabetes
      and with insulin concentration: interaction with smoking: the Coronary Artery
      Risk Development in Young Adults (CARDIA) Study.
AB  - Smoking is associated with low serum carotenoid concentrations. Prospective
      studies have found lower diabetes risk among persons with high-carotenoid diets.
      Whether diabetes risk is low in the rare smoker who has high serum carotenoid
      levels is unknown. The authors investigated the interaction of serum carotenoid
      concentrations and smoking with diabetes mellitus in 4,493 Black and White men
      and women aged 18-30 years in the Coronary Artery Risk Development in Young
      Adults (CARDIA) Study. The authors assessed 15-year (1985-2001) incident diabetes
      (148 cases), insulin concentration, and insulin resistance (homeostasis model
      assessment) in smokers and nonsmokers according to baseline levels of serum alpha
      carotene, beta-carotene, zeaxanthin, beta-cryptoxanthin, and lycopene. Diabetes
      incidence was inversely associated with the sum of carotenoid concentrations in
      nonsmokers (per standard deviation (SD) increase, relative hazard = 0.74, 95%
      confidence interval: 0.55, 0.99) but not in current smokers (relative hazard =
      1.13, 95% confidence interval: 0.83, 1.53) (p for interaction = 0.02). Similarly,
      year 15 insulin and insulin resistance values, adjusted for baseline levels, were
      inversely related to sum of carotenoids only in nonsmokers (per SD increase in
      insulin level, slope = -0.46 (p = 0.03); per SD increase in insulin resistance,
      slope = -0.14 (p = 0.01)). In CARDIA, higher serum carotenoid concentrations are
      associated with lower risk of diabetes and insulin resistance in nonsmokers but
      not in smokers.

PMID- 16597707
TI  - Trends in the prevalence, awareness, treatment, and control of cardiovascular
      disease risk factors among noninstitutionalized patients with a history of
      myocardial infarction and stroke.
AB  - Rates of hypertension, high low density lipoprotein (LDL) cholesterol, and
      diabetes mellitus awareness, treatment, and control for persons with a history of
      myocardial infarction and stroke were compared by using two nationally
      representative samples of the US population: the Third National Health and
      Nutrition Examination Survey in 1988-1994 (n = 1,004) and the National Health and
      Nutrition Examination Survey in 1999-2002 (n = 512). Estimated numbers of adult
      myocardial infarction and stroke survivors increased from 6.32 to 6.78 million
      and from 3.85 to 4.96 million, respectively. Among such survivors, awareness of a
      previous diagnosis of hypertension and prevalence of self-reported diabetes
      mellitus remained stable while awareness of high LDL cholesterol increased from
      43.3% to 60.2% (p < 0.01). Among those aware of their diagnosis, pharmacologic
      treatment for high LDL cholesterol increased from 33.1% to 78.4% and
      pharmacologic treatment for diabetes mellitus increased from 80.0% to 93.6%
      during this time (each p < 0.01), while pharmacologic treatment for hypertension
      increased nonsignificantly. Among those receiving pharmacologic treatment,
      hypertension and high LDL cholesterol control increased from 48.9% to 59.3% (p =
      0.05) and from 5.1% to 33.1% (p < 0.01), respectively. In contrast, glycemic
      control among diabetics decreased from 45.0% to 33.2% (p = 0.20). The number of
      US myocardial infarction and stroke survivors increased between 1988-1994 and
      1999-2002, and substantial improvements occurred in the awareness, treatment, and
      control of high LDL cholesterol in this population.

PMID- 16597708
TI  - Antibiotic use and risk of multiple sclerosis.
AB  - Some reports suggest that bacteria, including Chlamydophila pneumoniae, could be
      involved in the etiology of multiple sclerosis. If that is true, persons who used
      antibiotics active against these bacteria, compared with nonusers, might be at
      lower risk of multiple sclerosis. Using a 1993-2000 case-control study nested in
      the United Kingdom-based General Practice Research Database cohort, the authors
      identified 163 multiple sclerosis cases who were followed up for at least 3 years
      before their first symptoms (the index date). Up to 10 controls matched to the
      cases by age, sex, general practice, and time in the cohort were selected.
      Exposure to antibiotics was assessed through computerized medical records.
      Overall antibiotic use or use of antibiotics against C. pneumoniae was not
      associated with multiple sclerosis risk. However, use of penicillins in the 3
      years before the index date decreased the risk of developing a first attack of
      multiple sclerosis (odds ratio=0.5, 95% confidence interval: 0.3, 0.9 for those
      who used penicillins for >or=15 days compared with no use). In conclusion, use of
      antibiotics active against C. pneumoniae was not associated with a decreased risk
      of short-term multiple sclerosis. The observed lower risk of multiple sclerosis
      for penicillin users needs to be confirmed in other populations.

PMID- 16597709
TI  - Inhibition of nuclear factor-kappa B enhances the capacity of immature dendritic
      cells to induce antigen-specific tolerance in experimental autoimmune
      encephalomyelitis.
AB  - Autoimmune disorders develop as a result of deregulated immune responses that
      target self-antigens and cause destruction of healthy host tissues. Because
      dendritic cells (DCs) play an important role in the maintenance of peripheral
      immune tolerance, we are interested in identifying means of enhancing their
      therapeutic potential in autoimmune diseases. It is thought that during steady
      state, DCs are able to anergize potentially harmful T cells bearing T cell
      receptors that recognize self-peptide-major histocompatibility complexes. The
      tolerogenic capacity of DCs requires an immature phenotype, which is
      characterized by a reduced expression of costimulatory molecules. On the
      contrary, activation of antigen-specific naive T cells is enhanced by DC
      maturation, a process that involves expression of genes controlled by the
      transcription factor nuclear factor (NF)-kappaB. We evaluated the capacity of
      drugs that inhibit NF-kappaB to enhance the tolerogenic properties of immature
      DCs in the experimental autoimmune encephalomyelitis (EAE) model. We show that
      andrographolide, a bicyclic diterpenoid lactone, and rosiglitazone, a peroxisome
      proliferator-activated receptor gamma agonist, were able to interfere with NF
      kappaB activation in murine DCs. As a result, treated DCs showed impaired
      maturation and a reduced capacity to activate antigen-specific T cells.
      Furthermore, NF-kappaB-blocked DCs had an enhanced tolerogenic capacity and were
      able to prevent EAE development in mice. The tolerogenic feature was specific for
      myelin antigens and involved the expansion of regulatory T cells. These data
      suggest that NF-kappaB blockade is a potential pharmacological approach that can
      be used to enhance the tolerogenic ability of immature DCs to prevent detrimental
      autoimmune responses.

PMID- 16597710
TI  - Transport characteristics of a novel peptide transporter 1 substrate,
      antihypotensive drug midodrine, and its amino acid derivatives.
AB  - Midodrine is an oral drug for orthostatic hypotension. This drug is almost
      completely absorbed after oral administration and converted into its active form,
      1-(2',5'-dimethoxyphenyl)-2-aminoethanol) (DMAE), by the cleavage of a glycine
      residue. The intestinal H+-coupled peptide transporter 1 (PEPT1) transports
      various peptide-like drugs and has been used as a target molecule for improving
      the intestinal absorption of poorly absorbed drugs through amino acid
      modifications. Because midodrine meets these requirements, we examined whether
      midodrine can be a substrate for PEPT1. The uptake of midodrine, but not DMAE,
      was markedly increased in PEPT1-expressing oocytes compared with water-injected
      oocytes. Midodrine uptake by Caco-2 cells was saturable and was inhibited by
      various PEPT1 substrates. Midodrine absorption from the rat intestine was very
      rapid and was significantly inhibited by the high-affinity PEPT1 substrate
      cyclacillin, assessed by the alteration of the area under the blood concentration
      time curve for 30 min and the maximal concentration. Some amino acid derivatives
      of DMAE were transported by PEPT1, and their transport was dependent on the amino
      acids modified. In contrast to neutral substrates, cationic midodrine was taken
      up extensively at alkaline pH, and this pH profile was reproduced by a 14-state
      model of PEPT1, which we recently reported. These findings indicate that PEPT1
      can transport midodrine and contributes to the high bioavailability of this drug
      and that Gly modification of DMAE is desirable for a prodrug of DMAE.

PMID- 16597711
TI  - Sesamin metabolites induce an endothelial nitric oxide-dependent vasorelaxation
      through their antioxidative property-independent mechanisms: possible involvement
      of the metabolites in the antihypertensive effect of sesamin.
AB  - Sesamin, a major lignan in sesame seeds and oil, has been known to lower blood
      pressure in several types of experimental hypertensive animals. A recent study
      demonstrated that sesamin metabolites had in vitro radical-scavenging activities.
      Thus, we determined whether the antioxidative effect of sesamin metabolites
      modulate the vascular tone and contribute to the in vivo antihypertensive effect
      of sesamin. We used four demethylated sesamin metabolites: SC-1m (piperitol), SC
      1 (demethylpiperitol), SC-2m [(1R,2S,5R,6S)-6-(4-hydroxy-3-methoxyphenyl)-2-(3,4
      dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane], and SC-2 [(1R,2S,5R, 6S)-2,6
      bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo-[3,3,0]octane]. SC-1, SC-2m, and SC-2,
      but not SC-1m, exhibited potent radical-scavenging activities against the
      xanthine/xanthine oxidase-induced superoxide production. On the other hand, SC
      1m, SC-1, and SC-2m produced endothelium-dependent vasorelaxation in
      phenylephrine-precontracted rat aortic rings, whereas SC-2 had no effect. The SC
      1m- and SC-1-induced vasorelaxations were markedly attenuated by pretreatment
      with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (NOARG), or a
      soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1
      one. Neither SC-1m nor SC-1 changed the expression level of endothelial NOS
      protein in aortic tissues. The antihypertensive effects of sesamin feeding were
      not observed in chronically NOARG-treated rats or in deoxycorticosterone acetate
      salt-treated endothelial NOS-deficient mice. These findings suggest that the
      enhancement of endothelium-dependent vasorelaxation induced by sesamin
      metabolites is one of the important mechanisms of the in vivo antihypertensive
      effect of sesamin.

PMID- 16597712
TI  - A selective p38 alpha mitogen-activated protein kinase inhibitor reverses
      cartilage and bone destruction in mice with collagen-induced arthritis.
AB  - Destruction of cartilage and bone is a poorly managed hallmark of human
      rheumatoid arthritis (RA). p38 Mitogen-activated protein kinase (MAPK) has been
      shown to regulate key proinflammatory pathways in RA, including tumor necrosis
      factor alpha, interleukin (IL)-1beta, and cyclooxygenase-2, as well as the
      process of osteoclast differentiation. Therefore, we evaluated whether a p38alpha
      MAPK inhibitor, indole-5-carboxamide (SD-282), could modulate cartilage and bone
      destruction in a mouse model of RA induced with bovine type II collagen [collagen
      induced arthritis (CIA)]. In mice with early disease, SD-282 treatment
      significantly improved clinical severity scores, reduced bone and cartilage loss,
      and reduced mRNA levels of proinflammatory genes in paw tissue, including IL
      1beta, IL-6, and cyclooxygenase-2. Notably, SD-282 treatment of mice with
      advanced disease resulted in significant improvement in clinical severity scoring
      and paw swelling, a reversal in bone and cartilage destruction as assessed by
      histology, bone volume fraction and thickness, and three-dimensional image
      analysis. These changes were accompanied by reduced osteoclast number and lowered
      levels of serum cartilage oligomeric matrix protein, a marker of cartilage
      breakdown. Thus, in a model of experimental arthritis associated with significant
      osteolysis, p38alpha MAPK inhibition not only attenuates disease progression but
      also reverses cartilage and bone destruction in mice with advanced CIA disease.

PMID- 16597713
TI  - Feature configuration modulates effective connectivity.

PMID- 16597714
TI  - Surround suppression in the early visual system.

PMID- 16597715
TI  - Membrane-proximal region of glutamate receptor delta2 subunit is critical for
      long-term depression and interaction with protein interacting with C kinase 1 in
      a cerebellar Purkinje neuron.
AB  - The glutamate receptor delta2 subunit (GluRdelta2) is selectively expressed in
      cerebellar Purkinje neurons (PNs) and is involved in the long-term depression
      (LTD). However, little is known about the mechanism of its action. Acute
      expression of the wild-type GluRdelta2 in the GluRdelta2-deficient PN rescued the
      induction of LTD, suggesting the direct role of GluRdelta2 in LTD. To identify
      the critical region of GluRdelta2 necessary for LTD, we constructed and expressed
      various mutant GluRdelta2 proteins in the GluRdelta2-deficient PNs. The mutant
      GluRdelta2 possessing the membrane-proximal 21 aa residues in the C-terminal
      cytoplasmic region rescued the induction of LTD, whereas the mutant with membrane
      proximal 13 aa failed. In addition, overexpression of 865 approximately 871 aa of
      GluRdelta2 (corresponding to membrane-proximal 14-20 aa) fused to EGFP (enhanced
      green fluorescent protein) suppressed LTD in a wild-type PN. These results
      suggest that 865 approximately 871 aa of GluRdelta2 play an essential role in
      LTD. We next identified protein interacting with C kinase 1 (PICK1) as a molecule
      interacting with the membrane-proximal C-terminal region of GluRdelta2 by yeast
      two-hybrid screening. PICK1 plays an essential role in LTD. It colocalized with
      GluRdelta2 at spines of PNs, and immunoprecipitation assays showed that
      GluRdelta2 bound to PICK1 mainly through 865-871 aa. These results indicate that
      865-871 aa of GluRdelta2 are essential for both LTD and interaction with PICK1,
      and suggest that interaction between GluRdelta2 and PICK1 might be critical for
      the induction of LTD.

PMID- 16597716
TI  - No functional magnetic resonance imaging evidence for brightness and color
      filling-in in early human visual cortex.
AB  - The brightness and color of a surface depends on its contrast with nearby
      surfaces. For example, a gray surface can appear very light when surrounded by a
      black surface or dark when surrounded by a white surface. Some theories suggest
      that perceived surface brightness and color is represented explicitly by neural
      signals in cortical visual field maps; these neural signals are not initiated by
      the stimulus itself but rather by the contrast signals at the borders. Here, we
      use functional magnetic resonance imaging (fMRI) to search for such neural
      "filling-in" signals. Although we find the usual strong relationship between
      local contrast and fMRI response, when perceived brightness or color changes are
      induced by modulating a surrounding field, rather than the surface itself, we
      find there is no corresponding local modulation in primary visual cortex or other
      nearby retinotopic maps. Moreover, when we model the obtained fMRI responses, we
      find strong evidence for contributions of both local and long-range edge
      responses. We argue that such extended edge responses may be caused by neurons
      previously identified in neurophysiological studies as being brightness
      responsive, a characterization that may therefore need to be revised. We conclude
      that the visual field maps of human V1 and V2 do not contain filled-in,
      topographical representations of surface brightness and color.

PMID- 16597717
TI  - An implicit plan overrides an explicit strategy during visuomotor adaptation.
AB  - The relationship between implicit and explicit processes during motor learning,
      and for visuomotor adaptation in particular, is poorly understood. We set up a
      conflict between implicit and explicit processes by instructing subjects to
      counter a visuomotor rotation using a cognitive strategy in a pointing task.
      Specifically, they were told the exact nature of the directional perturbation, a
      rotation that directed them 45 degrees counterclockwise from the desired target,
      and they were instructed to counter it by aiming for the neighboring clockwise
      target, 45 degrees away. Subjects were initially successful in completely
      negating the rotation with this strategy. Surprisingly, however, they were unable
      to sustain explicit control and made increasingly large errors to the desired
      target. The cognitive strategy failed because subjects simultaneously adapted
      unconsciously to the rotation to the neighboring target. Notably, the rate of
      implicit adaptation to the neighboring target was not significantly different
      from rotation adaptation in the absence of an opposing explicit strategy. These
      results indicate that explicit strategies cannot substitute for implicit
      adaptation to a visuomotor rotation and are in fact overridden by the motor
      planning system. This suggests that the motor system requires that planned and
      executed trajectories remain congruous in visual space, and enforces this
      correspondence even at the expense of an opposing explicit task goal.

PMID- 16597718
TI  - Correlation-induced synchronization of oscillations in olfactory bulb neurons.
AB  - Oscillations are a common feature of odor-evoked and spontaneous activity in the
      olfactory system in vivo and in vitro and are thought to play an important role
      in information processing and memory in a variety of brain areas. Theoretical and
      experimental studies have described several mechanisms by which oscillations can
      be generated and synchronized. Here, we investigate the hypothesis that
      correlated noisy inputs are able to generate synchronous oscillations in
      olfactory bulb mitral cells in vitro. We consider several alternative mechanisms
      and conclude that olfactory bulb synchronous oscillations are likely to arise
      because of the response of uncoupled oscillating neurons to aperiodic but
      correlated inputs. This mechanism has been described theoretically, but we
      provide the first experimental evidence that such a mechanism may underlie
      synchronization in real neurons. In physiological experiments, we show that this
      mechanism can generate gamma-band oscillations in populations of olfactory bulb
      mitral cells. This mechanism synchronizes oscillatory firing by using shared fast
      fluctuations in stochastic inputs across neurons, without requiring any synaptic
      or electrical coupling. We discuss the properties and limitations of
      synchronization by this mechanism and suggest that it may underlie fast
      oscillations in many brain areas.

PMID- 16597719
TI  - Activity in the lateral intraparietal area predicts the goal and latency of
      saccades in a free-viewing visual search task.
AB  - The purpose of saccadic eye movements is to facilitate vision, by placing the
      fovea on interesting objects in the environment. Eye movements are not made for
      reward, and they are rarely restricted. Despite this, most of our knowledge about
      the neural genesis of eye movements comes from experiments in which specific eye
      movements are rewarded or restricted. Such experiments have demonstrated that
      activity in the lateral intraparietal (LIP) area of the monkey correlates with
      the monkey's planning of a memory-guided saccade or deciding where, on the basis
      of motion information, to make a saccade. However, other experiments have shown
      that neural activity in LIP can easily be dissociated from the generation of
      saccadic eye movements, especially when sophisticated behavioral paradigms
      dissociate the monkey's locus of attention from the goal of an intended saccade.
      In this study, we trained monkeys to report the results of a visual search task
      by making a nontargeting hand movement. Once the task began, the monkeys were
      entirely free to move their eyes, and rewards were not contingent on the monkeys
      making specific eye movements. We found that neural activity in LIP predicted not
      only the goal of the monkey's saccades but also their saccadic latencies.

PMID- 16597720
TI  - Cortical pain responses in human infants.
AB  - Despite the recent increase in our understanding of the development of pain
      processing, it is still not known whether premature infants are capable of
      processing pain at a cortical level. In this study, changes in cerebral
      oxygenation over the somatosensory cortex were measured in response to noxious
      stimulation using real-time near-infrared spectroscopy in 18 infants aged between
      25 and 45 weeks postmenstrual age. The noxious stimuli were heel lances performed
      for routine blood sampling; no blood tests were performed solely for the purpose
      of the study. Noxious stimulation produced a clear cortical response, measured as
      an increase in total hemoglobin concentration [HbT] in the contralateral
      somatosensory cortex, from 25 weeks (mean Delta[HbT] = 7.74 micromol/L; SE,
      1.10). Cortical responses were significantly greater in awake compared with
      sleeping infants, with a mean difference of 6.63 micromol/L [95% confidence
      interval (CI) limits: 2.35, 10.91 micromol/L; mean age, 35.2 weeks]. In awake
      infants, the response in the contralateral somatosensory cortex increased with
      age (regression coefficient, 0.698 micromol/L/week; 95% CI limits: 0.132, 1.265
      micromol/L/week) and the latency decreased with age (regression coefficient, 
      0.9861 micromol/L/week; 95% CI limits: -1.5361, -0.4361 micromol/L/week; age
      range, 25-38 weeks). The response was modality specific because no response was
      detected after non-noxious stimulation of the heel, even when accompanied by
      reflex withdrawal of the foot. We conclude that noxious information is
      transmitted to the preterm infant cortex from 25 weeks, highlighting the
      potential for both higher-level pain processing and pain-induced plasticity in
      the human brain from a very early age.

PMID- 16597721
TI  - Higher-dimensional neurons explain the tuning and dynamics of working memory
      cells.
AB  - Measurements of neural activity in working memory during a somatosensory
      discrimination task show that the content of working memory is not only stimulus
      dependent but also strongly time varying. We present a biologically plausible
      neural model that reproduces the wide variety of characteristic responses
      observed in those experiments. Central to our model is a heterogeneous ensemble
      of two-dimensional neurons that are hypothesized to simultaneously encode two
      distinct stimuli dimensions. We demonstrate that the spiking activity of each
      neuron in the population can be understood as the result of a two-dimensional
      state space trajectory projected onto the tuning curve of the neuron. The wide
      variety of observed responses is thus a natural consequence of a population of
      neurons with a diverse set of preferred stimulus vectors and response functions
      in this two-dimensional space. In addition, we propose a taxonomy of network
      topologies that will generate the two-dimensional trajectory necessary to exploit
      this population. We conclude by proposing some experimental indicators to help
      distinguish among these possibilities.

PMID- 16597722
TI  - Somatosensory cells in area PEc of macaque posterior parietal cortex.
AB  - PEc is an area defined on cytoarchitectural grounds, located in the posterior
      part of the superior parietal lobule of macaque brain (Pandya and Seltzer, 1982).
      The aim of this work was to assess whether passive somatosensory stimulation
      elicited responses in PEc neurons. Extracellular recordings were performed in
      three awake Macaca fascicularis. Passive somatosensory stimulation was performed
      in darkness, and eye movements were monitored continuously. Recording sites were
      assigned to different areas according to the cytoarchitectonic criteria described
      by Pandya and Seltzer (1982) and Luppino et al. (2005). Only recording sites
      within the limits of the cytoarchitecturally defined area PEc were taken into
      account in this work. Of 147 PEc cells, 83 (56%) were modulated by passive
      somatosensory stimulation. The majority of them (73%) responded to joint
      rotations, and 24% responded to tactile skin stimulation. The majority of PEc
      somatosensory responses (90%) were evoked by contralateral stimulation. Joint
      modulated cells were mostly activated by the upper limbs (82%). The majority of
      tactile receptive fields (61%) were located on the arms, and a minority was
      located on the legs and trunk. One-half of PEc somatosensory cells were
      polysensory, because they were sensitive to visual stimulation. The majority of
      PEc somatosensory cells were activated by active reaching movements.
      Somatosensory cells, somatosensory submodalities, and body part representations
      were not clustered in PEc subregions; in other words, PEc does not show a
      somatotopic organization. Although the caudal sector of the superior parietal
      lobule has been traditionally considered as a somatosensory area, this is the
      first demonstration of the presence of somatosensory cells in this cortical
      region.

PMID- 16597723
TI  - Inclusion body formation and neurodegeneration are parkin independent in a mouse
      model of alpha-synucleinopathy.
AB  - Mutations in the genes coding for alpha-synuclein and parkin cause autosomal
      dominant and autosomal-recessive forms of Parkinson's disease (PD), respectively.
      Alpha-synuclein is a major component of Lewy bodies, the proteinaceous
      cytoplasmic inclusions that are the pathological hallmark of idiopathic PD. Lewy
      bodies appear to be absent in cases of familial PD associated with mutated forms
      of parkin. Parkin is an ubiquitin E3 ligase, and it may be involved in the
      processing and/or degradation of alpha-synuclein, as well as in the formation of
      Lewy bodies. Here we report the behavioral, biochemical, and histochemical
      characterization of double-mutant mice overexpressing mutant human A53T alpha
      synuclein on a parkin null background. We find that the absence of parkin does
      not have an impact on the onset and progression of the lethal phenotype induced
      by overexpression of human A53T alpha-synuclein. Furthermore, all major
      behavioral, biochemical, and morphological characteristics of A53T alpha
      synuclein-overexpressing mice are not altered in parkin null alpha-synuclein
      overexpressing double-mutant mice. Our results demonstrate that mutant alpha
      synuclein induces neurodegeneration independent of parkin-mediated ubiquitin E3
      ligase activity in nondopaminergic systems and suggest that PD caused by alpha
      synuclein and parkin mutations may occur via independent mechanisms.

PMID- 16597724
TI  - Neural variability in premotor cortex provides a signature of motor preparation.
AB  - We present experiments and analyses designed to test the idea that firing rates
      in premotor cortex become optimized during motor preparation, approaching their
      ideal values over time. We measured the across-trial variability of neural
      responses in dorsal premotor cortex of three monkeys performing a delayed-reach
      task. Such variability was initially high, but declined after target onset, and
      was maintained at a rough plateau during the delay. An additional decline was
      observed after the go cue. Between target onset and movement onset, variability
      declined by an average of 34%. This decline in variability was observed even when
      mean firing rate changed little. We hypothesize that this effect is related to
      the progress of motor preparation. In this interpretation, firing rates are
      initially variable across trials but are brought, over time, to their
      "appropriate" values, becoming consistent in the process. Consistent with this
      hypothesis, reaction times were longer if the go cue was presented shortly after
      target onset, when variability was still high, and were shorter if the go cue was
      presented well after target onset, when variability had fallen to its plateau. A
      similar effect was observed for the natural variability in reaction time: longer
      (shorter) reaction times tended to occur on trials in which firing rates were
      more (less) variable. These results reveal a remarkable degree of temporal
      structure in the variability of cortical neurons. The relationship with reaction
      time argues that the changes in variability approximately track the progress of
      motor preparation.

PMID- 16597725
TI  - Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of
      the general anesthetic etomidate.
AB  - A fundamental objective of anesthesia research is to identify the receptors and
      brain regions that mediate the various behavioral components of the anesthetic
      state, including amnesia, immobility, and unconsciousness. Using complementary in
      vivo and in vitro approaches, we found that GABAA receptors that contain the
      alpha5 subunit (alpha5GABAARs) play a critical role in amnesia caused by the
      prototypic intravenous anesthetic etomidate. Whole-cell recordings from
      hippocampal pyramidal neurons showed that etomidate markedly increased a tonic
      inhibitory conductance generated by alpha5GABAARs, whereas synaptic transmission
      was only slightly enhanced. Long-term potentiation (LTP) of field EPSPs recorded
      in CA1 stratum radiatum was reduced by etomidate in wild-type (WT) but not alpha5
      null mutant (alpha5-/-) mice. In addition, etomidate impaired memory performance
      of WT but not alpha5-/- mice for spatial and nonspatial hippocampal-dependent
      learning tasks. The brain concentration of etomidate associated with memory
      impairment in vivo was comparable with that which increased the tonic inhibitory
      conductance and blocked LTP in vitro. The alpha5-/- mice did not exhibit a
      generalized resistance to etomidate, in that the sedative-hypnotic effects
      measured with the rotarod, loss of righting reflex, and spontaneous motor
      activity were similar in WT and alpha5-/- mice. Deletion of the alpha5 subunit of
      the GABAARs reduced the amnestic but not the sedative-hypnotic properties of
      etomidate. Thus, the amnestic and sedative-hypnotic properties of etomidate can
      be dissociated on the basis of GABAAR subtype pharmacology.

PMID- 16597726
TI  - Modulation of respiratory rhythmogenesis by chloride-mediated conductances during
      the perinatal period.
AB  - Respiratory rhythmogenesis is modulated by chloride-mediated conductances via
      GABAA and glycine receptors. In this study, we determine the actions of chloride
      mediated conductances on respiratory rhythmogenesis in perinatal rats from the
      time of inception of fetal inspiratory drive through to the newborn period. Data
      were obtained from perinatal rat models, including (1) recordings of nerve roots
      and neuronal population discharge from medullary slice and brainstem-spinal cord
      in vitro preparations, (2) gramicidin perforated-patch recordings of respiratory
      neurons in medullary slices, and (3) plethysmographic recordings from
      unanesthetized pups. The transition from excitatory to inhibitory effects on
      respiratory rhythmogenesis occurs at approximately embryonic day 19. By birth,
      GABA, glycine, and taurine all induce a hyperpolarization of the membrane
      potential in respiratory medullary neurons and a suppression of respiratory
      frequency. The age-dependant change in the actions of chloride-mediated
      conductances is regulated by the development of chloride cotransporters (KCC2 and
      NKCC1). The function of KCC2 chloride cotransporter is strongly modulated by
      [K+]o, which must be considered when evaluating responses observed using in vitro
      perinatal preparations.

PMID- 16597727
TI  - A biophysically based neural model of matching law behavior: melioration by
      stochastic synapses.
AB  - In experiments designed to uncover the neural basis of adaptive decision making
      in a foraging environment, neuroscientists have reported single-cell activities
      in the lateral intraparietal cortex (LIP) that are correlated with choice options
      and their subjective values. To investigate the underlying synaptic mechanism, we
      considered a spiking neuron model of decision making endowed with synaptic
      plasticity that follows a reward-dependent stochastic Hebbian learning rule. This
      general model is tested in a matching task in which rewards on two targets are
      scheduled randomly with different rates. Our main results are threefold. First,
      we show that plastic synapses provide a natural way to integrate past rewards and
      estimate the local (in time) "return" of a choice. Second, our model reproduces
      the matching behavior (i.e., the proportional allocation of choices matches the
      relative reinforcement obtained on those choices, which is achieved through
      melioration in individual trials). Our model also explains the observed
      "undermatching" phenomenon and points to biophysical constraints (such as finite
      learning rate and stochastic neuronal firing) that set the limits to matching
      behavior. Third, although our decision model is an attractor network exhibiting
      winner-take-all competition, it captures graded neural spiking activities
      observed in LIP, when the latter were sorted according to the choices and the
      difference in the returns for the two targets. These results suggest that neurons
      in LIP are involved in selecting the oculomotor responses, whereas rewards are
      integrated and stored elsewhere, possibly by plastic synapses and in the form of
      the return rather than income of choice options.

PMID- 16597728
TI  - Sympathetic sprouting drives hippocampal cholinergic reinnervation that prevents
      loss of a muscarinic receptor-dependent long-term depression at CA3-CA1 synapses.
AB  - Degeneration of septohippocampal cholinergic neurons results in memory deficits
      attributable to loss of cholinergic modulation of hippocampal synaptic circuits.
      A remarkable consequence of cholinergic degeneration is the sprouting of
      noradrenergic sympathetic fibers from the superior cervical ganglia into
      hippocampus. The functional impact of sympathetic ingrowth on synaptic physiology
      has never been investigated. Here, we report that, at CA3-CA1 synapses, a Hebbian
      form of long-term depression (LTD) induced by muscarinic M1 receptor activation
      (mLTD) is lost after medial septal lesion. Unexpectedly, expression of mLTD is
      rescued by sympathetic sprouting. These effects are specific because LTP and
      other forms of LTD are unaffected. The rescue of mLTD expression is coupled
      temporally with the reappearance of cholinergic fibers in hippocampus, as
      assessed by the immunostaining of fibers for VAChT (vesicular acetylcholine
      transporter). Both the cholinergic reinnervation and mLTD rescue are prevented by
      bilateral superior cervical ganglionectomy, which also prevents the noradrenergic
      sympathetic sprouting. The new cholinergic fibers likely originate from the
      superior cervical ganglia because unilateral ganglionectomy, performed when
      cholinergic reinnervation is well established, removes the reinnervation on the
      ipsilateral side. Thus, the temporal coupling of the cholinergic reinnervation
      with mLTD rescue, together with the absence of reinnervation and mLTD expression
      after ganglionectomy, demonstrate that the autonomic-driven cholinergic
      reinnervation is essential for maintaining mLTD after central cholinergic cell
      death. We have discovered a novel phenomenon whereby the autonomic and central
      nervous systems experience structural rearrangement to replace lost cholinergic
      innervation in hippocampus, with the consequence of preserving a form of LTD that
      would otherwise be lost as a result of cholinergic degeneration.

PMID- 16597729
TI  - Structural determinants of M-type KCNQ (Kv7) K+ channel assembly.
AB  - The ability of KCNQ (Kv7) channels to form hetero-oligomers is of high
      physiological importance, because heteromers of KCNQ3 with KCNQ2 or KCNQ5
      underlie the neuronal M-current, which modulates neuronal excitability. In KCNQ
      channels, we recently identified a C-terminal subunit interaction (si) domain
      that determines their subunit-specific assembly. Within this si domain, there are
      two motifs that comprise approximately 30 amino acid residues each and that
      exhibit a high probability for coiled-coil formation. Transfer of the first or
      the second coiled-coil (TCC) domain from KCNQ3 into the KCNQ1 scaffold resulted
      in chimeras KCNQ1(TCC1)Q3 and KCNQ1(TCC2)Q3, both of which coimmunoprecipitated
      with KCNQ2. However, only KCNQ1(TCC2)Q3 enhanced KCNQ2 currents and surface
      expression or exerted a strong dominant-negative effect on KCNQ2. Deletion of
      TCC2 within KCNQ2 yielded functional homomeric channels but prevented the current
      augmentation measured after coexpression of KCNQ2 and KCNQ3. In contrast,
      deleting TCC1 within KCNQ2 did not give functional homomeric KCNQ2 or heteromeric
      KCNQ2/KCNQ3 channels. Mutations that disrupted the predicted coiled-coil
      structure of TCC1 in KCNQ2 or KCNQ3 abolished channel activity after expressing
      these constructs singly or in combination, whereas helix-breaking mutations in
      TCC2 of KCNQ2 gave functional homomeric channels but prevented the
      heteromerization with KCNQ3. In contrast, KCNQ3 carrying a coiled-coil disrupting
      mutation in TCC2 hetero-oligomerized with KCNQ2. Our data suggest that the TCC1
      domains of KCNQ2 and KCNQ3 are required to form functional homomeric as well as
      heteromeric channels, whereas both TCC2 domains facilitate an efficient transport
      of heteromeric KCNQ2/KCNQ3 channels to the plasma membrane.

PMID- 16597730
TI  - The dynamics of spatiotemporal response integration in the somatosensory cortex
      of the vibrissa system.
AB  - Spatiotemporal response integration across the neural receptive field (RF) is a
      general feature of sensory coding and has an important role in shaping responses
      to naturalistic stimuli. In the primary somatosensory cortex of the rat vibrissa
      pathway, such integration across the vibrissa array strongly shapes the coding of
      spatiotemporally distributed deflections. Using a spatiotemporal paired-pulse
      paradigm, this study revealed that fundamentally different types of pairwise
      interactions have similar qualitative behavior but that the magnitude, latency,
      and precision of the neural responses depend on the specific RF components being
      engaged. In all cases, however, increase in the suppression of response magnitude
      accompanied a lengthening of latency and a decrease in response precision.
      Furthermore, nonlinear interactions evoked by stimulation of multiple RF
      subregions strongly influence both response magnitude and timing to more complex
      sequences. Despite their complexity, such response interactions are highly
      predictable from elementary pairwise interactions. To understand the functional
      role of spatiotemporal interactions in coding, we developed a response model that
      incorporated the experimentally measured modulations in response magnitude,
      latency, and precision induced by cross-vibrissa interactions. Simulations of a
      simplified textural discrimination task indicate that spatiotemporal interactions
      enhance discrimination under certain stimulus time scales. This improvement
      follows from a nonlinear response property that acts to restore the neural
      response in the face of suppression. Together, the present findings highlight the
      role of response integration in shaping single-cell responses and provide
      predictions about how changes in response parameters influence coding accuracy.

PMID- 16597731
TI  - Somatic sensation of hand-object interactive movement is associated with activity
      in the left inferior parietal cortex.
AB  - Manipulation of objects and tool-use are known to be controlled by a network of
      frontal motor and parietal areas. Here, we investigate which of these areas are
      associated with the somatic sensation of hand-object interactive movement using
      functional magnetic resonance imaging. To dissociate the sensation of movement
      from the motor control commands, we used a new kinesthetic illusion. Twelve
      blindfolded right-handed participants placed the palm of their right or left hand
      on an object (a ball). Simultaneously, we vibrated the tendon of the wrist
      extensor muscle. This elicited the illusion that the wrist is flexing and the
      touched object is also moving along with the hand (hand-object illusion). As
      controls, we vibrated the skin surface over the nearby bone, which does not
      elicit any illusions, or we vibrated the tendon when the hand did not touch the
      object, which only generates the illusory flexion of the hand. We found that the
      hand-object illusion specifically activated the left inferior parietal lobule
      (IPL) (supramarginal gyrus and parietal operculum, including cytoarchitectonic
      areas ip1 and op1) and area 44. The left IPL was activated both during the hand
      object illusions with the right and left hands, and the activity was greater than
      in the right corresponding parietal region, suggesting a dominant role of the
      left hemisphere. We conclude that the left IPL is involved in the somatic
      perception of hand-object interactive movement and suggest that the underlying
      mechanism is the somatic integration of internal information about the body and
      external information about the object.

PMID- 16597732
TI  - Different roles for amygdala central nucleus and substantia innominata in the
      surprise-induced enhancement of learning.
AB  - Within most modern learning theories, the discrepancy between expected and
      obtained outcomes ("prediction error" or "surprise") is a critical determinant of
      the acquisition of learned associations. The results of studies from many
      laboratories show that the surprising omission of an expected event may enhance
      attention to stimuli that remain present, such that subsequent learning about
      those stimuli is enhanced. A series of reports from our laboratories demonstrated
      that these surprise-induced enhancements of stimulus associability depend on
      circuitry that includes the amygdala central nucleus (CeA), the cholinergic
      neurons in the sublenticular substantia innominata/nucleus basalis
      magnocellularis (SI/nBM), as well as certain cortical projections of these latter
      neurons. In this study, we found very different roles for CeA and SI/nBM in
      surprise-induced enhancements of stimulus associability. In four experiments that
      used transient inactivation techniques, we found that surprise-induced
      enhancement of subsequent learning about a stimulus depended on intact CeA
      function at the time of surprise but not when more rapid learning was
      subsequently expressed. In contrast, normal SI/nBM function was critical to the
      expression of enhanced learning but was not necessary when surprise was induced.
      These data suggest that these two components of the so-called "extended amygdala"
      serve distinct roles in the encoding and retrieval of information used in
      modulating attention to stimuli in associative learning. Additional circuitry
      linking these brain regions may also be important in the maintenance of that
      information.

PMID- 16597733
TI  - Inhibition of apoptosis by P2Y2 receptor activation: novel pathways for neuronal
      survival.
AB  - Cell survival is an essential function in the development and maintenance of the
      nervous system. We demonstrate here a previously unappreciated role for
      extracellular nucleotide signaling through the P2Y2 receptor in the survival of
      neurons: PC12 (pheochromocytoma 12) cells and dorsal root ganglion neurons are
      protected from serum starvation-induced apoptosis by ATP, UTP, and ATPgammaS, an
      effect mediated via P2Y2 receptors, as demonstrated by small interfering RNA and
      genetic knock-out models. This protection occurs independently of neurophin
      signaling but requires Src activation of ERK (extracellular signal-regulated
      kinase) and Akt. Moreover, ATPgammaS and NGF act synergistically to enhance
      neuronal survival through enhanced TrkA signaling. The results, which define a
      novel mechanism for inhibition of apoptosis, implicate parallel, interacting
      systems--extracellular nucleotides/P2Y2 receptors and neurotrophin/TrkA--to
      sustain neuronal survival.

PMID- 16597734
TI  - Amphetamine exposure enhances habit formation.
AB  - Performance of instrumental actions in rats is initially sensitive to
      postconditioning changes in reward value, but after more extended training,
      behavior comes to be controlled by stimulus-response (S-R) habits that are no
      longer goal directed. To examine whether sensitization of dopaminergic systems
      leads to a more rapid transition from action-outcome processes to S-R habits, we
      examined performance of amphetamine-sensitized rats in an instrumental
      devaluation task. Animals were either sensitized (7 d, 2 mg/kg/d) before training
      (experiment 1) or sensitized between training and testing (experiment 2). Rats
      were trained to press a lever for a reward (three sessions) and were then given a
      test of goal sensitivity by devaluation of the instrumental outcome before
      testing in extinction. Control animals showed selective sensitivity to
      devaluation of the instrumental outcome. However, amphetamine sensitization
      administered before training caused the animals' responding to persist despite
      the changed value of the reinforcer. This deficit resulted from an inability to
      use representations of the outcome to guide behavior, because a reacquisition
      test confirmed that all of the animals had acquired an aversion to the
      reinforcer. In experiment 2, post-training sensitization did not disrupt normal
      goal-directed behavior. These findings indicate that amphetamine sensitization
      leads to a rapid progression from goal-directed to habit-based responding but
      does not affect the performance of established goal-directed actions.

PMID- 16597735
TI  - Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of
      nuclear factor-kappaB in the frontal cortex and hippocampus via glucocorticoid
      secretion.
AB  - Although the anti-inflammatory actions of glucocorticoids (GCs) are well
      established in the periphery, these stress hormones can increase inflammation
      under some circumstances in the brain. The transcription factor nuclear factor
      kappaB (NF-kappaB), which is inhibited by GCs, regulates numerous genes central
      to inflammation. In this study, the effects of stress, GCs, and NMDA receptors on
      lipopolysaccharide (LPS)-induced activation of NF-kappaB in the brain were
      investigated. One day after chronic unpredictable stress (CUS), nonstressed and
      CUS rats were treated with saline or LPS and killed 2 h later. CUS potentiated
      the increase in LPS-induced activation of NF-kappaB in frontal cortex and
      hippocampus but not in the hypothalamus. This stress effect was blocked by
      pretreatment of rats with RU-486, an antagonist of the GC receptor. MK-801 [(+)-5
      methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an NMDA
      receptor antagonist, also reduced the effect of LPS in all three brain regions.
      However, the combined antagonism of both GC and NMDA receptors produced no
      further reduction in NF-kappaB activation when compared with the effect of each
      treatment alone. Our results indicate that stress, via GC secretion, can increase
      LPS-induced NF-kappaB activation in the frontal cortex and hippocampus, agreeing
      with a growing literature demonstrating proinflammatory effects of GCs.

PMID- 16597736
TI  - The GxGD motif of presenilin contributes to catalytic function and substrate
      identification of gamma-secretase.
AB  - Gamma-secretase is a multisubunit aspartyl protease complex that catalyzes
      intramembrane cleavage of beta-amyloid precursor protein (APP), a substrate key
      to Alzheimer's disease pathogenesis, and of Notch, a substrate crucial for cell
      differentiation. How gamma-secretase recognizes and selects substrates is
      currently barely understood. Recent data suggest that its subunit nicastrin
      serves as an initial substrate receptor, which might subsequently forward
      substrates to the active site domain located in its catalytic subunit presenilin
      (PS), where an additional substrate binding site has been proposed. We now used
      an active site domain swapping approach of PS1 with its most distant homolog,
      spermatogenesis defective (SPE-4), to identify sequence determinants in this
      region. Strikingly, when the active site domain of PS1 was exchanged with that of
      SPE-4, the chimeric protein, PS1/SPE-4(6/7), supported APP but not Notch
      processing. In addition, PS1/SPE-4(6/7) was strongly impaired in Caenorhabditis
      elegans Notch signaling in vivo. Mapping experiments identified a single amino
      acid at position x of the GxGD motif, which contains one of the two active site
      aspartates, to be responsible for the observed defect in Notch processing and
      signaling. Our data thus implicate a role of the GxGD motif in catalytic function
      and substrate identification of gamma-secretase.

PMID- 16597737
TI  - NG2 glial cells provide a favorable substrate for growing axons.
AB  - NG2 cells (polydendrocytes) comprise an abundant glial population that is widely
      and uniformly distributed throughout the developing and mature CNS and are
      identified by the expression of the NG2 proteoglycan at the cell surface.
      Although recent electrophysiological studies suggest that they are capable of
      receiving signals from axon terminals, other studies, based on the finding that
      the NG2 molecule itself induces growth cone collapse, have led to a widely held
      speculation that NG2 cells themselves also repel and inhibit growing axons. In
      this study, we have examined the effects of rat NG2 cells on growing hippocampal
      and neocortical axons in vitro and in vivo. NG2 cells did not repel growing axons
      but promoted their growth in vitro, and axonal growth cones formed extensive
      contacts with NG2 cells both in vitro and in the developing corpus callosum.
      Punctate immunoreactivity for fibronectin and laminin was found to be colocalized
      with NG2 on the surface of NG2 cells. Altering the level of cell surface NG2
      expression had no effect on the growth-promoting effects of NG2 cells on growing
      axons. Thus, our study indicates that NG2 cells are not inhibitory to growing
      axons but provide an adhesive substrate for axonal growth cones and promote their
      growth even in the presence of elevated levels of the NG2 proteoglycan. These
      findings suggest a novel role for NG2 cells in facilitating axonal growth during
      development and regeneration.

PMID- 16597738
TI  - The mother or the fetus? 11beta-hydroxysteroid dehydrogenase type 2 null mice
      provide evidence for direct fetal programming of behavior by endogenous
      glucocorticoids.
AB  - Low birth weight associates with increased susceptibility to adult
      cardiometabolic and affective disorders spawning the notion of fetal
      "programming." Prenatal exposure to excess glucocorticoids may be causal. In
      support, maternal stress or treatment during pregnancy with dexamethasone (which
      crosses the placenta) or inhibitors of fetoplacental 11beta-hydroxysteroid
      dehydrogenase type 2 (11beta-HSD2), the physiological "barrier" to maternal
      glucocorticoids, reduces birth weight and programs permanent offspring
      hypertension, hyperglycemia, and anxiety behaviors. It remains uncertain whether
      such effects are mediated indirectly via altered maternal function or directly on
      the fetus and its placenta. To dissect this critical issue, we mated 11beta
      HSD2(+/-) mice such that each pregnant female produces +/+, +/-, and -/-
      offspring and compared them with offspring of homozygous wild-type and -/-
      matings. We show that 11beta-HSD2(-/-) offspring of either +/- or -/- mothers
      have lower birth weight and exhibit greater anxiety than 11beta-HSD2(+/+)
      littermates. This provides clear evidence for the key role of fetoplacental
      11beta-HSD2 in prenatal glucocorticoid programming.

PMID- 16597739
TI  - Deletion of presenilin 1 hydrophilic loop sequence leads to impaired gamma
      secretase activity and exacerbated amyloid pathology.
AB  - gamma-Secretase processing of the amyloid precursor protein (APP) generates
      Abeta40 and Abeta42, peptides that constitute the principal components of the
      beta-amyloid plaque pathology of Alzheimer's disease (AD). The gamma-secretase
      activity is executed by a high-molecular-weight complex of which presenilin 1
      (PS1) is an essential component. PS1 is a multi-pass membrane protein, and the
      large hydrophilic loop domain between transmembrane domains 6 and 7 has been
      shown to interact with various proteins. To determine the physiological function
      of the loop domain, we created a strain of PS1 knock-in mice in which the exon
      10, which encodes most of the hydrophilic loop sequence, was deleted from the
      endogenous PS1 gene. We report here that the homozygous exon 10-deleted mice are
      viable but exhibit drastically reduced gamma-secretase cleavage at the Abeta40,
      but not the Abeta42, site. Surprisingly, this reduction of Abeta40 is associated
      with exacerbated plaque pathology when expressed on APP transgenic background.
      Thus, the PS1 loop plays a regulatory role in gamma-secretase processing, and
      decreased Abeta40, not increased Abeta42 is likely the cause for the accelerated
      plaque deposition in these animals. Our finding supports a protective role of
      Abeta40 against amyloid pathology and raises the possibility that impaired gamma
      secretase activity could be the basis for AD pathogenesis in general.

PMID- 16597740
TI  - Behavioral and anatomical interactions between dopamine and corticotropin
      releasing factor in the rat.
AB  - The neuropeptide corticotropin-releasing factor (CRF) is believed to play a role
      in a number of psychiatric conditions, including anxiety disorders and
      depression. In the present study, male Sprague Dawley rats were used to examine
      the behavioral effects of altering dopamine transmission on CRF-enhanced startle,
      a behavioral assay believed to reflect stress- or anxiety-like states. Systemic
      administration of the selective dopamine D1 receptor antagonist SCH 23390 [R(+)-7
      chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrochloride] (0, 0.01, 0.05, 0.1, 0.5 mg/kg) dose dependently blocked the
      effect of CRF (1 microg, i.c.v.) on startle at doses that had no effect on
      baseline startle response. Immunohistochemical studies showed that most CRF
      containing cells in the dorsolateral division of the bed nucleus of the stria
      terminalis (BSTld), part of the critical brain area mediating CRF-enhanced
      startle, are surrounded by a dense plexus of tyrosine hydroxylase (TH)-positive
      fibers. Intra-BSTld injections of the retrograde tracer Fluorogold (FG) into the
      TH field identified neurons in the major dopaminergic areas (A8-A10), but not the
      major noradrenergic areas [A5, A6 (locus ceruleus), A7], as a significant source
      of TH-positive innervation. The majority of FG-filled cells double-labeled for TH
      were found in the dorsocaudal A10 cell group (A10dc) located in the
      periaqueductal gray area. Together, these data suggest that neuronal regulation
      of the BSTld by specific dopaminergic pathways and receptors may be an important
      mechanism for controlling CRF-dependent moods and affective states. These data
      also suggest that compounds with D1 receptor antagonist properties might have
      anxiolytic-like effects that could be useful for treating conditions associated
      with hyperactive CRF systems.

PMID- 16597741
TI  - A transient receptor potential vanilloid 4-dependent mechanism of hyperalgesia is
      engaged by concerted action of inflammatory mediators.
AB  - The transient receptor potential vanilloid 4 (TRPV4) is a primary afferent
      transducer that plays a crucial role in neuropathic hyperalgesia for osmotic and
      mechanical stimuli, as well as in inflammatory mediator-induced hyperalgesia for
      osmotic stimuli. In view of the clinical importance of mechanical hyperalgesia in
      inflammatory states, the present study investigated the role of TRPV4 in
      mechanical hyperalgesia induced by inflammatory mediators and the second
      messenger pathways involved. Intradermal injection of either the inflammogen
      carrageenan or a soup of inflammatory mediators enhanced the nocifensive paw
      withdrawal reflex elicited by hypotonic or mechanical stimuli in rat. Spinal
      administration of TRPV4 antisense oligodeoxynucleotide blocked the enhancement
      without altering baseline nociceptive threshold. Similarly, in TRPV4(-/-) knock
      out mice, inflammatory soup failed to induce any significant mechanical or
      osmotic hyperalgesia. In vitro investigation showed that inflammatory mediators
      engage the TRPV4-mediated mechanism of sensitization by direct action on
      dissociated primary afferent neurons. Additional behavioral observations
      suggested that multiple mediators are necessary to achieve sufficient activation
      of the cAMP pathway to engage the TRPV4-dependent mechanism of hyperalgesia. In
      addition, direct activation of protein kinase A or protein kinase C epsilon, two
      pathways that mediate inflammation-induced mechanical hyperalgesia, also induced
      hyperalgesia for both hypotonic and mechanical stimuli that was decreased by
      TRPV4 antisense and absent in TRPV4(-/-) mice. We conclude that TRPV4 plays a
      crucial role in the mechanical hyperalgesia that is generated by the concerted
      action of inflammatory mediators present in inflamed tissues.

PMID- 16597742
TI  - Cortical inputs and GABA interneurons imbalance projection neurons in the
      striatum of parkinsonian rats.
AB  - The striatum receives massive cortical excitatory inputs and is densely
      innervated by dopamine. Striatal projection neurons form either the direct or
      indirect pathways. Models of Parkinson's disease propose that dopaminergic
      degeneration imbalances both pathways, although direct electrophysiological
      evidence is lacking. Here, striatal neurons were identified by
      electrophysiological criteria and Neurobiotin labeling combined with either
      immunohistochemistry or in situ hybridization. Their spontaneous discharge
      activity and spike response to cortical stimulation were recorded in vivo in
      anesthetized rats rendered hemi-parkinsonian by 6-hydroxydopamine. We showed that
      striatonigral neurons (direct pathway) were inhibited whereas striatopallidal
      neurons (indirect pathway) were activated by dopaminergic lesion. We also
      identified, with antidromic stimulations, corticostriatal neurons that
      preferentially innervate striatonigral or striatopallidal neurons and showed that
      dopaminergic depletion selectively decreased the spontaneous activity of the
      former. Therefore, dopamine degeneration induces a cascade of imbalances that
      spread out of the basal ganglia and affect the whole basal ganglia-thalamo
      cortical circuits. Fast-spiking GABA interneurons provide potent feedforward
      inhibition of striatal projection neurons. We showed here that these interneurons
      narrowed the time window of the responses of projection neurons to cortical
      stimulation. In the dopamine-depleted striatum, because the intrinsic activity of
      these interneurons was not altered, their feedforward inhibition worsened the
      striatal imbalance. Indeed, the time window of the evoked responses was narrower
      for striatonigral neurons and wider for striatopallidal neurons. Therefore, after
      dopaminergic depletion, cortical inputs and GABA interneurons might imbalance
      striatal projection neurons and represent two novel nondopaminergic mechanisms
      that might secondarily contribute to the pathophysiology of Parkinson's disease.

PMID- 16597744
TI  - Comments on music, ethology, and evolution.

PMID- 16597745
TI  - Probing the evolutionary origins of music perception.
AB  - Empirical data have recently begun to inform debates on the evolutionary origins
      of music. In this paper we discuss some of our recent findings and related
      theoretical issues. We claim that theories of the origins of music will be
      usefully constrained if we can determine which aspects of music perception are
      innate, and, of those, which are uniquely human and specific to music.
      Comparative research in nonhuman animals, particularly nonhuman primates, is thus
      critical to the debate. In this paper we focus on the preferences that
      characterize most humans' experience of music, testing whether similar
      preferences exist in nonhuman primates. Our research suggests that many
      rudimentary acoustic preferences, such as those for consonant over dissonant
      intervals, may be unique to humans. If these preferences prove to be innate in
      humans, they may be candidates for music-specific adaptations. To establish
      whether such preferences are innate in humans, one important avenue for future
      research will be the collection of data from different cultures. This may be
      facilitated by studies conducted over the internet.

PMID- 16597746
TI  - The conformal motive in birdsong, music, and language: an introduction.
AB  - Human song and music are part of what may be called a ritual stratum of human
      culture. As such, they involve special behaviors and neural mechanisms with an
      uneven but interesting distribution in nature. This may be turned to account not
      only for shedding light on the biological background of human song and music, but
      also for elucidating the nature of the cultural traditions within which these
      arts are practiced and elaborated. The purpose of this chapter is accordingly
      threefold: (1) to highlight the uniqueness of human culture compared to that of
      other primates by defining and contrasting two very different types of traditions
      that coexist within it: those of instrumental culture and those of ritual
      culture; (2) to outline the crucial role of the mechanism of vocal learning as an
      enabling device for ritual culture, specifically, by way of the well-studied
      behavioral biology of birdsong; and (3) to introduce the conformal motive as a so
      far neglected, but essential, aspect of the neural mechanisms required for vocal
      learning. Taken together, these considerations will then be used to sketch some
      of the roles this postulated conformal motive appears to play in human culture,
      stratified into instrumental, ritual, and language traditions. Some of the
      implications of this perspective for our understanding of a number of issues
      related to the human facility for imitation, expressive mimesis, and deliberate
      teaching are also briefly touched upon.

PMID- 16597747
TI  - The evolution of music in comparative perspective.
AB  - In this paper, I briefly review some comparative data that provide an empirical
      basis for research on the evolution of music making in humans. First, a brief
      comparison of music and language leads to discussion of design features of music,
      suggesting a deep connection between the biology of music and language. I then
      selectively review data on animal "music." Examining sound production in animals,
      we find examples of repeated convergent evolution or analogy (the evolution of
      vocal learning of complex songs in birds, whales, and seals). A fascinating but
      overlooked potential homology to instrumental music is provided by manual
      percussion in African apes. Such comparative behavioral data, combined with
      neuroscientific and developmental data, provide an important starting point for
      any hypothesis about how or why human music evolved. Regarding these functional
      and phylogenetic questions, I discuss some previously proposed functions of
      music, including Pinker's "cheesecake" hypothesis; Darwin's and others' sexual
      selection model; Dunbar's group "grooming" hypothesis; and Trehub's caregiving
      model. I conclude that only the last hypothesis receives strong support from
      currently available data. I end with a brief synopsis of Darwin's model of a
      songlike musical "protolanguage," concluding that Darwin's model is consistent
      with much of the available evidence concerning the evolution of both music and
      language. There is a rich future for empirical investigations of the evolution of
      music, both in investigations of individual differences among humans, and in
      interspecific investigations of musical abilities in other animals, especially
      those of our ape cousins, about which we know little.

PMID- 16597748
TI  - Neuronal mechanisms underlying the perception of pitch and harmony.
AB  - Temporal processing of periodic acoustic signals in the auditory brain stem
      provides an explanation for pitch perception and the natural preference of our
      hearing system for harmonic relationships in music. Experimental evidence is
      reviewed for a corresponding neuronal model of correlation analysis and the
      spatial representation of pitch information along the second neural axis of the
      auditory system.

PMID- 16597749
TI  - Tonality and nonlinear resonance.
AB  - We outline a theory of tonality that predicts tonal stability, attraction, and
      categorization based on the principles of nonlinear resonance. Perception of
      tonality is the natural consequence of neural resonance, arising from central
      auditory nonlinearities.

PMID- 16597751
TI  - The relationship of music to the melody of speech and to syntactic processing
      disorders in aphasia.
AB  - Two new empirical studies address the relationship between music and language.
      The first focuses on melody and uses research in phonetics to investigate the
      long-held notion that instrumental music reflects speech patterns in a composer's
      native language. The second focuses on syntax and addresses the relationship
      between musical and linguistic syntactic processing via the study of aphasia, an
      approach that has been explored very little. The results of these two studies add
      to a growing body of evidence linking music and language with regard to
      structural patterns and brain processing.

PMID- 16597752
TI  - Musical and linguistic processing in song perception.
AB  - One approach to comparing the neural bases of language and music is through the
      use of song, which is a unique and ecological combination of these two cognitive
      domains. In song, language and music are merged into one acoustic signal with two
      salient dimensions. By manipulating either the linguistic or musical dimensions
      (or both) of song and studying their relationships, it is possible to gain
      important information about the neural networks underlying language and music
      cognition. We will present a brief review followed by recent behavioral,
      electrophysiological, and neuroimaging studies concerned with the functional and
      structural relationships of music and language. These results, together with the
      previous studies in the field, help understanding whether the different levels of
      music and language processing are independent or interactive.

PMID- 16597753
TI  - Neural correlates of rapid spectrotemporal processing in musicians and
      nonmusicians.
AB  - Our results suggest that musical training alters the functional anatomy of rapid
      spectrotemporal processing, resulting in improved behavioral performance along
      with a more efficient functional network primarily involving traditional language
      regions. This finding may have important implications for improving
      language/reading skills, especially in children struggling with dyslexia.

PMID- 16597754
TI  - Spectral and temporal processing in the human auditory cortex--revisited.
AB  - We use novel noise-like sound stimuli to identify cortical areas in which the
      functional magnetic resonance signal covaries with spectral and temporal acoustic
      complexity. The results support a model of hemispheric functional asymmetry for
      fine-grained spectral and fast temporal processing.

PMID- 16597755
TI  - Influence of musical training on pitch processing: event-related brain potential
      studies of adults and children.
AB  - The aim of this experiment was to determine whether eight weeks of musical
      training based on pitch processing could help eight-year-old children detect
      pitch changes in language. Results show that a relatively short exposure (eight
      weeks) to pitch processing in music exerts some influence on pitch processing in
      language. Therefore, these results are in line with the hypothesis that common
      processes may underlie pitch processing in language and in music.

PMID- 16597757
TI  - Implicit investigations of tonal knowledge in nonmusician listeners.
AB  - By mere exposure to musical pieces in everyday life, Western listeners acquire
      sensitivity to the regularities of the tonal system and to the context dependency
      of musical sounds. This implicitly acquired tonal knowledge allows nonmusician
      listeners to perceive relationships among musical events and to develop
      expectations for future events that then influence the processing of these
      events. The musical priming paradigm is one method of the indirect investigation
      of listeners' tonal knowledge. It investigates the influence of a preceding
      context (with its musical structures and relationships) on the processing of a
      musical target event, without asking participants for direct evaluations.
      Behavioral priming data have provided evidence for facilitated processing of
      musically related events in comparison to unrelated and less-related events. The
      sensitivity of implicit investigations is further shown by I.R., a patient with
      severe amusia, showing spared implicit knowledge of music. Finally, the priming
      paradigm allows us to investigate the neural correlates of musical structure
      processing. Two fMRI studies reported the implication of inferior frontal regions
      in musical priming, contrasting related and unrelated events, as well as finer
      structural manipulations contrasting in-key events.

PMID- 16597758
TI  - Brain networks that track musical structure.
AB  - As the functional neuroimaging literature grows, it becomes increasingly apparent
      that music and musical activities engage diverse regions of the brain. In this
      paper I discuss two studies to illustrate that exactly which brain areas are
      observed to be responsive to musical stimuli and tasks depends on the tasks and
      the methods used to describe the tasks and the stimuli. In one study, subjects
      listened to polyphonic music and were asked to either orient their attention
      selectively to individual instruments or in a divided or holistic manner across
      multiple instruments. The network of brain areas that was recruited changed
      subtly with changes in the task instructions. The focus of the second study was
      to identify brain regions that follow the pattern of movement of a continuous
      melody through the tonal space defined by the major and minor keys of Western
      tonal music. Such an area was identified in the rostral medial prefrontal cortex.
      This observation is discussed in the context of other neuroimaging studies that
      implicate this region in inwardly directed mental states involving decisions
      about the self, autobiographical memory, the cognitive regulation of emotion,
      affective responses to musical stimuli, and familiarity judgments about musical
      stimuli. Together with observations that these regions are among the last to
      atrophy in Alzheimer disease, and that these patients appear to remain responsive
      to autobiographically salient musical stimuli, very early evidence is emerging
      from the literature for the hypothesis that the rostral medial prefrontal cortex
      is a node that is important for binding music with memories within a broader
      music-responsive network.

PMID- 16597759
TI  - Neural encoding and retrieval of sound sequences.
AB  - Although considerable progress has been made recently in our understanding of the
      coding of complex sounds in the cerebral cortex, the processing and storage of
      tone sequences is still poorly understood. We have used functional magnetic
      resonance imaging to identify brain mechanisms involved in the encoding and
      retrieval of melodies by studying the anticipation of familiar music. The results
      suggest a specific role for each of the following brain structures: the anterior
      part of the right superior temporal cortex, the right inferior frontal cortex and
      anterior insula, the left anterior prefrontal cortex, the lateral cerebellum, and
      the anterior cingulate. In a separate study, we investigated single-neuron
      responses in the auditory cortex of awake behaving monkeys to alternating tone
      sequences that in humans evoke the perception of "streaming." Depending on the
      frequency separation between the tones, an initial single stream may segregate
      into two streams after a build-up period of several seconds. The neural responses
      in the monkeys' primary auditory cortex (A1) mirror the psychophysical time
      course extremely well, suggesting that habituation within A1 may be one reason
      for stream segregation. However, the higher auditory and prefrontal areas found
      to be activated by musical melodies are expected to interact with primary areas
      in both bottom-up and top-down fashion to bring about the perceptual organization
      of sound sequences.

PMID- 16597760
TI  - Functional neuroimaging of semantic and episodic musical memory.
AB  - The distinction between episodic and semantic memory has become very popular
      since it was first proposed by Tulving in 1972. So far, very few
      neuropsychological, psychophysical, and imaging studies have related to the
      mnemonic aspects of music, notably on the long-term memory features, and
      practically nothing is known about the functional anatomy of long-term memory for
      music. Numerous functional imaging studies have shown that retrieval from
      semantic and episodic memory is subserved by distinct neural networks. For
      instance, the HERA model (hemispheric encoding/retrieval asymmetry) ascribes to
      the left prefrontal cortex a preferential role in the encoding process of
      episodic material and the recall of semantic information, while the right
      prefrontal cortex would preferentially operate in the recall of episodic
      information. However, these results were essentially obtained with verbal and
      visuo-spatial material. We have done a study to determine the neural substrates
      underlying the semantic and episodic components of music using familiar and
      nonfamiliar melodic tunes. Two distinct patterns of activations were found:
      bilateral activation of the middle and superior frontal areas and precuneus for
      episodic memory, and activation of the medial and orbital frontal cortex
      bilaterally, left angular gyrus, and the anterior part of the left middle and
      superior temporal gyri for semantic memory. We discuss these findings in light of
      the available neuropsychological data obtained in brain-damaged subjects and
      functional neuroimaging studies.

PMID- 16597761
TI  - Neurophysiology and neuroanatomy of pitch perception: auditory cortex.
AB  - We present original results and review literature from the past fifty years that
      address the role of primate auditory cortex in the following perceptual
      capacities: (1) the ability to perceive small differences between the pitches of
      two successive tones; (2) the ability to perceive the sign (i.e., direction) of
      the pitch difference [higher (+) vs. lower (-)]; and (3) the ability to abstract
      pitch constancy across changes in stimulus acoustics. Cortical mechanisms
      mediating pitch perception are discussed with respect to (1) gross and
      microanatomical distribution; and (2) candidate neural coding schemes.
      Observations by us and others suggest that (1) frequency-selective neurons in
      primary auditory cortex (A1) and surrounding fields play a critical role in fine
      grained pitch discrimination at the perceptual level; (2) cortical mechanisms
      that detect pitch differences are neuroanatomically dissociable from those
      mediating pitch direction discrimination; (3) cortical mechanisms mediating
      perception of the "missing fundamental frequency (F0)" are neuroanatomically
      dissociable from those mediating pitch perception when F0 is present; (4)
      frequency-selective neurons in both right and left A1 contribute to pitch change
      detection and pitch direction discrimination; (5) frequency-selective neurons in
      right A1 are necessary for normal pitch direction discrimination; (6) simple
      codes for pitch that are based on single- and multiunit firing rates of frequency
      selective neurons face both a "hyperacuity problem" and a "pitch constancy
      problem"-that is, frequency discrimination thresholds for pitch change direction
      and pitch direction discrimination are much smaller than neural tuning curves
      predict, and firing rate patterns change dramatically under conditions in which
      pitch percepts remain invariant; (7) cochleotopic organization of frequency
      selective neurons bears little if any relevance to perceptual acuity and pitch
      constancy; and (8) simple temporal codes for pitch capable of accounting for
      pitches higher than a few hundred hertz have not been found in the auditory
      cortex. The cortical code for pitch is therefore not likely to be a function of
      simple rate profiles or synchronous temporal patterns. Studies motivated by
      interest in the neurophysiology and neuroanatomy of music perception have helped
      correct longstanding misconceptions about the functional role of auditory cortex
      in frequency discrimination and pitch perception. Advancing knowledge about the
      neural coding of pitch is of fundamental importance to the future design of
      neurobionic therapies for hearing loss.

PMID- 16597762
TI  - Aspects of multisensory perception: the integration of visual and auditory
      information in musical experiences.
AB  - One of the requirements for being a successful musical conductor is to be able to
      locate sounds instantaneously in time and space. Because this requires the
      integration of auditory and visual information, the purpose of this study was to
      examine multisensory processing in conductors and a matched set of control
      subjects. Subjects participated in a series of behavioral tasks, including pitch
      discrimination, temporal-order judgment (TOJ), and target localization.
      Additionally, fMRI scans were done on a subset of subjects who performed a
      multisensory TOJ task. Analyses of behavioral data indicate that, in the auditory
      realm, conductors were more accurate in both pitch discrimination and TOJs as
      well as in locating targets in space. Furthermore, these same subjects also
      demonstrated a benefit from the combination of auditory and visual information
      that was not observed in control subjects when locating visual targets. Finally,
      neural substrates in BA 37, 39/40 were identified as potential areas underlying
      the conductors' superior multisensory TOJs. Data collection and analyses are
      ongoing and will lead to an improved understanding of multisensory integration in
      a complex, musical behavior.

PMID- 16597763
TI  - A network for sensory-motor integration: what happens in the auditory cortex
      during piano playing without acoustic feedback?
AB  - Playing a musical instrument requires efficient auditory as well as motor
      processing. We provide evidence for the existence of a neuronal network of
      secondary and higher-order areas belonging to the auditory and motor modality
      that is important in the integration of auditory and motor domains.

PMID- 16597764
TI  - The power of listening: auditory-motor interactions in musical training.
AB  - We trained musically naive subjects to play a short piano melody by ear in a
      fully monitored computerized environment and tested their potential to acquire a
      functional linkage between actions and sounds. Individual notes that were simply
      acoustic pretraining signals became "physically meaningful" posttraining. In
      addition, we found preliminary evidence that passive listening to a newly learned
      musical piece can enhance motor performance in the absence of physical practice.

PMID- 16597765
TI  - The mental space of pitch height.
AB  - Through stimulus-response compatibility we tested whether sound frequency (pitch
      height) elicits a mental spatial representation. Musically untrained and, mostly,
      trained participants were shown a stimulus-response compatibility effect (Spatial
      Musical Association of Response Codes or SMARC effect). When response
      alternatives were either vertically or horizontally aligned, performance was
      better when the lower (or leftward) button had to be pressed in response to a low
      sound and the upper (or rightward) button had to be pressed in response to a high
      sound, even when pitch height was irrelevant to the task.

PMID- 16597767
TI  - Music listening and cognitive abilities in 10- and 11-year-olds: the blur effect.
AB  - The spatial abilities of a large sample of 10 and 11 year olds were tested after
      they listened to contemporary pop music, music composed by Mozart, or a
      discussion about the present experiment. After being assigned at random to one of
      the three listening experiences, each child completed two tests of spatial
      abilities. Performance on one of the tests (square completion) did not differ as
      a function of the listening experience, but performance on the other test (paper
      folding) was superior for children who listened to popular music compared to the
      other two groups. These findings are consistent with the view that positive
      benefits of music listening on cognitive abilities are most likely to be evident
      when the music is enjoyed by the listener.

PMID- 16597768
TI  - Examining rhythm and melody processing in young children using FMRI.
AB  - While it is often reported that musical experience can have positive effects on
      cognitive development in young children, the neural basis of such potential
      effects remains relatively unexplored. Employing functional magnetic resonance
      imaging (fMRI) for such research presents as many challenges as possibilities,
      not least of which is the fact that young children can find it difficult to
      remain still and attentive for long periods of time. Here we describe an fMRI
      scanning protocol designed specifically for young children using short scanning
      runs, a sparse temporal sampling data acquisition technique, simple rhythmic and
      melodic discrimination tasks with a button-press response, and a child-oriented
      preparation session. Children were recruited as part of a large-scale
      longitudinal study examining the effects of musical training on cognitive
      development and the structure and function of the growing brain. Results from an
      initial analysis of 33 children and from the first five children to be re-scanned
      after musical training indicate that our scanning protocol is successful and that
      activation differences can be detected both between conditions and over time.

PMID- 16597769
TI  - Effects of music training on the child's brain and cognitive development.
AB  - Research has revealed structural and functional differences in the brains of
      adult instrumental musicians compared to those of matched nonmusician controls,
      with intensity/duration of instrumental training and practice being important
      predictors of these differences. Nevertheless, the differential contributions of
      nature and nurture to these differences are not yet clear. The musician
      nonmusician comparison is an ideal model for examining whether and, if so, where
      such functional and structural brain plasticity occurs, because musicians acquire
      and continuously practice a variety of complex motor, auditory, and multimodal
      skills (e.g., translating visually perceived musical symbols into motor commands
      while simultaneously monitoring instrumental output and receiving multisensory
      feedback). Research has also demonstrated that music training in children results
      in long-term enhancement of visual-spatial, verbal, and mathematical performance.
      However, the underlying neural bases of such enhancements and whether the
      intensity and duration of instrumental training or other factors, such as
      extracurricular activities, attention, motivation, or instructional methods can
      contribute to or predict these enhancements are yet unknown. Here we report the
      initial results from our studies examining the brain and cognitive effects of
      instrumental music training on young children in a longitudinal study and a cross
      sectional comparison in older children. Further, we present a comparison of the
      results in these children's studies with observations from our cross-sectional
      studies with adults.

PMID- 16597770
TI  - Investigating the relationship of music and language in children: influences of
      musical training and language impairment.
AB  - Language and music are human universals involving perceptually discrete elements
      organized in hierarchically structured sequences. The set of principles governing
      the combination of these structural elements into sequences is known as syntax. A
      violation of expectancies concerning syntactic regularities may be reflected by
      two ERP components: the ERAN (early right anterior negativity) and the ELAN
      (early left anterior negativity). The ERAN is evoked by a violation of musical
      regularities, whereas the ELAN is linked to syntax processing in the language
      domain. There is evidence from adult data to suggest that both ERAN and ELAN are,
      at least partly, generated in the same brain regions. Therefore, it seems
      plausible to expect transfer effects between music and language due to shared
      processing resources. Moreover, the ERAN is larger in adults with formal musical
      training (musicians) than in those without, indicating that more specific
      representations of musical regularities lead to heightened musical expectancies.
      The aim of this study is to investigate these issues in child development. We
      conducted two experimental sessions with the same participants and compared
      children with and without musical training (11 years old) and children with or
      without language impairment (5 years old). In a music experiment, the reactions
      to chord sequences ending either with a (regular) tonic or with an (irregular)
      supertonic were compared. For a language experiment we used syntactically correct
      and incorrect sentences. Preliminary results show that an ERAN is present in both
      groups and appears to have a larger amplitude in musically trained children. In
      addition, there are indications of an enhanced negativity in response to a
      syntactic violation in the musically trained children. The relationship between
      the ERP components is, moreover, manifested in the finding that an ERAN is
      present in linguistically nonimpaired children at the age of 5 years but not in
      children with language impairment of the same age.

PMID- 16597771
TI  - Temporal entrainment of cognitive functions: musical mnemonics induce brain
      plasticity and oscillatory synchrony in neural networks underlying memory.
AB  - In a series of experiments, we have begun to investigate the effect of music as a
      mnemonic device on learning and memory and the underlying plasticity of
      oscillatory neural networks. We used verbal learning and memory tests
      (standardized word lists, AVLT) in conjunction with electroencephalographic
      analysis to determine differences between verbal learning in either a spoken or
      musical (verbal materials as song lyrics) modality. In healthy adults, learning
      in both the spoken and music condition was associated with significant increases
      in oscillatory synchrony across all frequency bands. A significant difference
      between the spoken and music condition emerged in the cortical topography of the
      learning-related synchronization. When using EEG measures as predictors during
      learning for subsequent successful memory recall, significantly increased
      coherence (phase-locked synchronization) within and between oscillatory brain
      networks emerged for music in alpha and gamma bands. In a similar study with
      multiple sclerosis patients, superior learning and memory was shown in the music
      condition when controlled for word order recall, and subjects were instructed to
      sing back the word lists. Also, the music condition was associated with a
      significant power increase in the low-alpha band in bilateral frontal networks,
      indicating increased neuronal synchronization. Musical learning may access
      compensatory pathways for memory functions during compromised PFC functions
      associated with learning and recall. Music learning may also confer a
      neurophysiological advantage through the stronger synchronization of the neuronal
      cell assemblies underlying verbal learning and memory. Collectively our data
      provide evidence that melodic-rhythmic templates as temporal structures in music
      may drive internal rhythm formation in recurrent cortical networks involved in
      learning and memory.

PMID- 16597772
TI  - Quantifying tone deafness in the general population.
AB  - Many people reach adulthood without acquiring significant music performance
      skills (singing or instrumental playing). A substantial proportion of these
      adults consider that this has come about because they are "not musical." Some of
      these people may be "true" congenital amusics, characterized by specific and
      substantial anomalies in the processing of musical pitch and rhythm sequences,
      while at the same time displaying normal processing of speech and language. It is
      likely, however, that many adults who believe that they are unmusical are
      neurologically normal. We could call these adults "false" amusics. Acquisition of
      musical competence has multiple personal, social, and environmental precursors.
      Deficiencies in these areas may lead to lack of musical achievement, despite the
      fact that an individual possesses the necessary underlying capacities. Adults may
      therefore self-define as "unmusical" or "tone-deaf" for reasons unconnected to
      any underlying anomaly. This paper reports on two linked research studies. The
      first is an interview study with adults defining themselves as tone-deaf or
      unmusical. The interview schedule was designed to discover what criteria are
      being used in their self-definitions. Preliminary results suggest that
      performance criteria (e.g., judging oneself as unable to sing) play a major role,
      even for people who claim and demonstrate no perceptual deficits. The second
      study reports progress on the development of new subtests for a revised version
      of the Montreal Battery for the Evaluation of Amusia (MBEA, Peretz et al., 2003).
      This currently contains six tests that allow for the assessment of melodic
      perception: contour, intervals, scale, rhythm, meter, and recognition memory. The
      MBEA does not assess two capacities that are generally accepted as central to
      normal music cognition: harmony and emotion. The development and norming of the
      emotion subtest will be described. When completed, the MBEA(R) will form a robust
      screening device for use with the general population, whose purpose is to
      discriminate "true" from "false" amusics. Such discrimination is essential to
      achieve a better understanding of the variety of causes of low musical
      achievement.

PMID- 16597773
TI  - Does music instruction improve fine motor abilities?
AB  - The fine motor abilities of children who participated in two years of piano
      instruction and those who had never received formal music training were compared
      before and after the instruction. A significant improvement in fine motor skills
      was found only for the children who received the lessons, and a significant
      difference in the speed of response was found between the two groups at the end
      of the two years of instruction. The innumerable opportunities to assess, refine,
      and time their motor responses to specific stimuli during musical practice and
      the availability of constant evaluative feedback (i.e., sound) may allow
      musicians to improve the accuracy and speed of perceiving and responding to
      relevant stimuli.

PMID- 16597774
TI  - The effect of early musical training on adult motor performance: evidence for a
      sensitive period in motor learning.
AB  - This experiment demonstrates that musicians who began training before age seven
      perform better on a rhythmic tapping task than musicians who began after the age
      of seven, when the two groups are matched for years of experience. These results
      support the idea that there may be a sensitive period in childhood for motor
      training, similar to that observed for language learning.

PMID- 16597776
TI  - Scientific perspectives on music therapy.
AB  - What needs to be done on the long road to evidence-based music therapy? First of
      all, an adequate research strategy is required. For this purpose the general
      methodology for therapy research should be adopted. Additionally, music therapy
      needs a variety of methods of allied fields to contribute scientific findings,
      including mathematics, natural sciences, behavioral and social sciences, as well
      as the arts. Pluralism seems necessary as well as inevitable. At least two major
      research problems can be identified, however, that make the path stony: the
      problem of specificity and the problem of eclecticism. Neuroscientific research
      in music is giving rise to new ideas, perspectives, and methods; they seem to be
      promising prospects for a possible contribution to a theoretical and empirical
      scientific foundation for music therapy. Despite the huge heterogeneity of
      theoretical approaches in music therapy, an integrative model of working
      ingredients in music therapy is useful as a starting point for empirical studies
      in order to question what specifically works in music therapy. For this purpose,
      a heuristic model, consisting of five music therapy working factors (attention
      modulation, emotion modulation, cognition modulation, behavior modulation, and
      communication modulation) has been developed by the Center for Music Therapy
      Research (Viktor Dulger Institute) in Heidelberg. Evidence shows the
      effectiveness of music therapy for treating certain diseases, but the question of
      what it is in music therapy that works remains largely unanswered. The authors
      conclude with some questions to neuroscientists, which we hope may help elucidate
      relevant aspects of a possible link between the two disciplines.

PMID- 16597777
TI  - Outcome research in music therapy: a step on the long road to an evidence-based
      treatment.
AB  - Music therapy is the therapeutic use of music and musical activities in the
      treatment of somatic and mental diseases. In the last decades it has developed
      from a quasi-professional working field into an increasingly evidence-based
      treatment for various diseases. Selected outcome studies that were carried out in
      order to give music therapy a scientific and empirical base are presented in this
      article. Results show that music therapy is an effective intervention for
      patients with chronic pain, children with migraine, and patients suffering from
      chronic tinnitus. This positive outcome, in combination with the observed
      moderate to large effect sizes in different metanalyses, provides evidence for
      the use of music therapy in specific clinical fields. Future research should
      focus on studies that compare well-defined music therapy interventions to
      standard treatment.

PMID- 16597778
TI  - Music therapy research in Ibero-American countries: an overview focused on
      assessment and clinical evaluation.
AB  - The aim of this article is to present an overview of some contemporary ideas
      concerning the status of music therapy research in Ibero-American countries, with
      a focus on assessment and clinical evaluation of music therapy clinical practice.

PMID- 16597779
TI  - The future of music in therapy and medicine.
AB  - The understanding of music's role and function in therapy and medicine is
      undergoing a rapid transformation, based on neuroscientific research showing the
      reciprocal relationship between studying the neurobiological foundations of music
      in the brain and how musical behavior through learning and experience changes
      brain and behavior function. Through this research the theory and clinical
      practice of music therapy is changing more and more from a social science model,
      based on cultural roles and general well-being concepts, to a neuroscience-guided
      model based on brain function and music perception. This paradigm shift has the
      potential to move music therapy from an adjunct modality to a central treatment
      modality in rehabilitation and therapy.

PMID- 16597781
TI  - Musical difficulties are rare: a study of "tone deafness" among university
      students.
AB  - This study was concerned with self-reported "tone deafness" and its possible
      relationship to congenital amusia. Nearly 17% of over 2,000 first-year psychology
      students at Queen's University self-reported tone deafness. Two hundred students
      were recruited from this pool of students, comprising 100 who reported tone
      deafness and 100 who reported that they were not tone-deaf (NTD). The study
      contained two parts. In part 1, participants completed the six tests of the
      Montreal Battery of Evaluation of Amusia (MBEA) developed by Peretz and
      collaborators. In part 2, participants completed an extensive questionnaire
      designed to elicit details about musical experiences, abilities, training, and
      interests. Twenty-eight questionnaire items allowing a quantitative response were
      subjected to factor analysis. Four orthogonal components emerged from the
      analysis. The components reflected self-report of (1) vocal production, (2) music
      instruction, (3) listening attitudes, and (4) childhood memories of musical
      environment. Results for each of the MBEA tests and composite scores for all
      tests were regressed on participants' factor scores. The best and significant
      predictors of the MBEA scores were factor I and factor II, followed by factor
      III. Factor scores accounted for a higher percentage of the variance in MBEA
      composite test results (27%) than the self-report of tone deafness alone (7%).
      The musical difficulties revealed by the MBEA test results for some participants
      warrant further attention and study. However, an encouraging conclusion from the
      MBEA results is that many individuals who consider themselves "tone-deaf" may
      not, in fact, have perceptual difficulties, and these individuals should be
      supported in any of their efforts to proceed with music enjoyment and
      instruction.

PMID- 16597782
TI  - Musical behavior in a neurogenetic developmental disorder: evidence from Williams
      Syndrome.
AB  - This paper reviews a series of studies performed to assess the musical abilities
      and behaviors of individuals with Williams syndrome, a neurogenetic developmental
      disorder, in the hope of eventually being able to link genes, neurodevelopment,
      and cognition. Two questionnaire studies addressing the role of music in everyday
      life, and unusual reactions to sound, are described. Additionally, the findings
      from two empirical behavioral studies and a neuroimaging study are reviewed. The
      findings show that individuals with Williams syndrome tend to be more engaged in
      musical activities than others, and I report a possible neuroanatomical correlate
      of this engagement, with increased activation in the right amygdala to music and
      to noise. Williams syndrome represents a compelling model of the relationship
      between genes, brains, and such complex cognitive behaviors as music.

PMID- 16597783
TI  - Changing the brain through therapy for musicians' hand dystonia.
AB  - Focal hand dystonia is a disorder in which sensory and motor anomalies emerge
      that appear to be grounded in maladaptive routes of cortical plasticity.
      Remodeling cortical networks through sensory-motor retuning (SMR), we achieved
      long-term reduction in the symptoms of focal hand dystonia.
      Magnetoencephalography confirmed that SMR modified the representational cortex of
      the fingers, whereby the representation of the affected hand was reorganized so
      that it resembled more the organization of the non-affected side. Furthermore, we
      observed differences in abnormal tactile acuity between patients with musician's
      cramp and those with writer's cramp: Using two-point finger discrimination,
      dystonic musicians showed perceptual asymmetry between hands, while writer's
      cramp patients did not. To further evaluate the occurrence of collateral
      disturbances in focal dystonia, we assessed the clinical histories of 101
      affected musicians. An important finding from this study was that dystonic
      musicians who play a similar first and second instrument reported a continuous
      worsening of their symptoms. In addition, collateral disturbances appeared with a
      shorter delay when more than one instrument was played. Taken together, these
      studies suggest that (1) neurological dysfunction can be reversed by context
      specific training protocols, (2) specific symptomatic and etiological differences
      among various forms of focal hand dystonia might result from different behavioral
      experiences and their central representation, and (3) the spread of symptoms
      might be prevented by avoiding training that implies movement patterns similar to
      the main affected task, and by reducing the amount of task-associated movement
      behavior.

PMID- 16597784
TI  - Music to electric ears: pitch and timbre perception by cochlear implant patients.
AB  - The sounds of music play with many perceptual dimensions. We devised a set of
      psychophysical procedures to better understand how recipients of cochlear
      implants perceive basic sound attributes involved in music listening.

PMID- 16597786
TI  - Enhanced P1-N1 auditory evoked potential in patients with musicians' cramp.
AB  - Auditory evoked potentials (AEPs) were examined in patients with musician's cramp
      (focal dystonia) in order to determine whether these patients have
      electrophysiological changes in a sensory system that is not usually associated
      with symptoms. All participants were professional guitarists and were required to
      listen to 2,000 monaurally presented stimuli (middle C, with duration of 7 ms).
      During one block, 250 stimuli were presented to one ear. Once a block was
      finished, another block was presented in the other ear; in total there were eight
      blocks of stimuli. During this task, EEGs from 10 scalp electrodes and one
      bipolar eye channel were continuously recorded. There were no significant latency
      or topographical differences in the electrophysiological recordings. However,
      there was a significant group difference in the peak-to-peak amplitude of the P1
      N1a component. The patients had a larger peak-to-peak difference than controls
      (1.63 vs. 0.62 microV). The P1 and N1a are cortically generated potentials.
      Patients with focal dystonia had an increase in activity compared to controls
      when processing simple auditory stimuli. Such changes in electrophysiological
      responses may be a result of increases in excitation or lack of inhibition;
      alternatively the changes may represent cross-modal maladaptive plasticity from
      the somatosensory modality to the auditory modality. Thus, this study provides
      further evidence that patients with focal dystonia have alterations of the
      central nervous system that are not limited to their symptomatic sensory domain.

PMID- 16597787
TI  - Time course of retrieval and movement preparation in music performance.
AB  - Music performance requires that musicians represent many different kinds of
      sequence structure: musicians must remember which pitch to produce, when to
      produce it, and how to produce it (with what movements). The time course of item
      retrieval and movement preparation processes during music performance are
      considered. Serially ordered stage models of retrieval, in which item retrieval
      ends before movement preparation begins, are compared with interactive cascade
      models, in which the time course of both processes overlap, permitting
      interaction. Evidence from transfer of learning paradigms, production errors, and
      anticipatory movements, as measured in motion capture, are described. This early
      evidence suggests different time courses for item retrieval (slower, earlier)
      than for movement preparation (faster, later) with significant temporal overlap
      during music performance.

PMID- 16597788
TI  - Neural control of rhythmic sequences.
AB  - We investigated whether the temporal structure of movement sequences can be
      represented and learned independently of their ordinal structure, and whether
      some brain regions are particularly important for temporal sequence performance.
      Using a learning transfer design, we found evidence for independent temporal
      representations: learning a spatiotemporal sequence facilitated learning its
      temporal and ordinal structure alone; learning a temporal and an ordinal
      structure facilitated learning of a sequence where the two were coupled. Second,
      learning of temporal structures was found during reproduction of sequential
      stimuli with random ordinal structure, suggesting independent mechanisms for
      temporal learning. We then used functional magnetic resonance imaging to
      investigate the neural control of sequences during well-learned performance. The
      temporal and ordinal structures of the sequences were varied in a 2 x 2 factorial
      design. A dissociation was found between brain regions involved in ordinal and
      temporal control, the latter mainly involving the presupplementary motor area,
      the inferior frontal gyrus and precentral sulcus, and the superior temporal gyri.
      Finally, in a second fMRI experiment, well-learned temporal sequences were
      performed with the left or right index fingers, or using rhythmic speech. The
      overlap in brain activity during performance with the different effectors
      included a similar set of brain regions as that found in the first fMRI
      experiment: the supplementary motor area (SMA), the superior temporal gyrus, and
      the inferior frontal cortex. We thus suggest that this set of regions is
      important for abstract, movement-independent, temporal sequence control. This
      organization may be important for increased flexibility in voluntarily timed
      motor tasks.

PMID- 16597789
TI  - A neurocognitive approach to music reading.
AB  - Music reading offers a unique perspective on the acquisition of a notational
      system. Many people cannot read music, but a large proportion are motivated to
      learn. Musical literacy is therefore amenable to studies of acquisition in a way
      that language literacy is not. The studies reviewed here investigate how musical
      symbols on the page are decoded into a musical response. The studies address the
      nature of the mental representations used in music reading, as well as their
      instantiation within the brain. The results of a musical Stroop paradigm are
      described, in which musical notation was present but irrelevant for task
      performance. The presence of musical notation produced systematic effects on
      reaction time, demonstrating that reading of the written note, like the written
      word, is obligatory for those who are musically literate. Spatial interference
      tasks are also described that suggest that music reading, at least for the
      pianist, can be characterized as a set of vertical to horizontal mappings. These
      behavioral findings are mirrored by the results of an fMRI training study in
      which musically untrained adults were taught to read music and play piano
      keyboard over a period of three months. Specific learning-related changes were
      seen in the superior parietal cortex and fusiform gyrus, for melody reading and
      rhythm reading, respectively. These changes are suggested to correspond to the
      acquisition of processes that deal with the extraction of spatial and featural
      properties of notation, respectively.

PMID- 16597790
TI  - Structural, functional, and perceptual differences in Heschl's gyrus and musical
      instrument preference.
AB  - The musical pitch of harmonic complex sounds, such as instrumental sounds, is
      perceived primarily by decoding either the fundamental pitch (keynote) or
      spectral aspects of the stimuli, for example, single harmonics. We divided 334
      professional musicians, including symphony orchestra musicians, 75 amateur
      musicians, and 54 nonmusicians, into either fundamental pitch listeners or
      spectral pitch listeners. We observed a strong correlation between pitch
      perception preference and asymmetry of brain structure and function in the pitch
      sensitive lateral areas of Heschl's gyrus (HG), irrespective of musical ability.
      In particular, fundamental pitch listeners exhibited both larger gray matter
      volume measured using magnetic resonance imaging (MRI) and enhanced P50m activity
      measured using magnetoencephalography (MEG) in the left lateral HG, which is
      sensitive to rapid temporal processing. Their chosen instruments were percussive
      or high-pitched instruments that produce short, sharp, or impulsive tones (e.g.,
      drums, guitar, piano, trumpet, or flute). By contrast, spectral pitch listeners
      exhibited a dominant right lateral HG, which is known to be sensitive to slower
      temporal and spectral processing. Their chosen instruments were lower-pitched
      melodic instruments that produce rather sustained tones with characteristic
      changes in timbre (e.g., bassoon, saxophone, french horn, violoncello, or organ).
      Singers also belonged to the spectral pitch listeners. Furthermore, the absolute
      size of the neural HG substrate depended strongly on musical ability. Overall, it
      is likely that both magnitude and asymmetry of lateral HG, and the related
      perceptual mode, may have an impact on preference for particular musical
      instruments and on musical performance.

PMID- 16597791
TI  - Differences in gray matter between musicians and nonmusicians.
AB  - Voxel-based morphometry is used to examine differences in cerebral morphology
      between musicians and nonmusicians. Principal results show differences in gray
      matter concentration in the right auditory cortex.

PMID- 16597792
TI  - Tapping in synchrony to auditory rhythms: effect of temporal structure on
      behavior and neural activity.
AB  - This study examines how synchronizing movements to auditory rhythms affects
      behavioral performance and neural activity as assessed using fMRI. Subjects
      perform worse as they tap along with increasingly complex musical rhythms, with
      responses becoming progressively asynchronous. This behavioral change also
      correlates with increasing neural activity in several motor-related brain
      regions, such as the cerebellum and premotor cortex (medial and lateral),
      highlighting the role of these areas in auditory-motor interactions during
      temporal processing.

PMID- 16597795
TI  - Investigating emotion with music: neuroscientific approaches.
AB  - This article briefly reviews the few functional imaging studies conducted so far
      on the investigation of emotion with music. Basically, these studies showed
      involvement of limbic and paralimbic cerebral structures (such as amygdala,
      hippocampus, parahippocampal gyrus, temporal poles, insula, ventral striatum,
      orbitofronal, as well as cingulate cortex) during the processing of music with
      emotional valence (such as pleasant or unpleasant). The second part of this
      article highlights the role of unexpected musical events for the elicitation of
      emotional responses. Recent studies suggest that music-syntactically irregular
      chords elicit changes in electrodermal activity, and that such chords activate
      orbital frontolateral cortex, as well as the amygdala (that is, brain structures
      that have been implicated in emotion processing). The third part of this article
      mentions findings on the temporal dynamics of emotion (that is, changes in the
      physiological correlates of emotion processing over time). This issue has so far
      been mainly neglected in the functional imaging (and psychophysiological)
      literature.

PMID- 16597793
TI  - Neural substrates governing audiovocal integration for vocal pitch regulation in
      singing.
AB  - The integration of auditory feedback with the vocal motor system is essential for
      singing, because precise control of vocal pitch is necessary to produce notes and
      melodies accurately. We used singing tasks with fMRI to determine the neural
      substrates involved in audiovocal integration. In tasks that specifically
      required monitoring of auditory feedback and pitch control, neural activity
      increased in the anterior cingulate cortex and insula, which suggests that these
      regions may play a special role in audiovocal integration.

PMID- 16597796
TI  - Effects of prior exposure on music liking and recognition in patients with
      temporal lobe lesions.
AB  - Prior exposure to music typically increases liking. This manifestation of
      implicit memory can be dissociated from explicit memory recognition. To examine
      the contribution of the medial temporal lobe to musical preference and
      recognition, we tested patients with either left (LTL) or right (RTL) temporal
      lobe lesions as well as normal control (NC) participants using the procedure of
      Peretz et al. The results in the affect task showed that NC and LTL participants
      preferred the studied over nonstudied melodies, thereby demonstrating an implicit
      exposure effect on liking judgments, whereas RTL patients failed to exhibit this
      effect. Explicit recognition was impaired in both LTL and RTL patients as
      compared to NC participants. On the basis of these findings, we suggest that RTL
      structures play a critical role in the formation of melody representations that
      support both priming and memory recognition, whereas LTL structures are more
      involved in the explicit retrieval of melodies. Furthermore, we were able to test
      an amnesic patient (PC) with bilateral lesions of the temporal lobe. In this
      case, the exposure effect on liking was also absent. However, repeated exposure
      to melodies was found to enhance both liking and recognition judgments. This
      remarkable sparing of memory observed through melody repetition suggests that
      extensive exposure may assist both implicit and explicit memory in the presence
      of global amnesia.

PMID- 16597797
TI  - The time course of emotional responses to music.
AB  - Two empirical studies investigate the time course of emotional responses to
      music. In the first one, musically trained and untrained listeners were required
      to listen to 27 musical excerpts and to group those that conveyed a similar
      emotional meaning. In one condition, the excerpts were 25 seconds long on
      average. In the other condition, excerpts were as short as 1 second. The
      groupings were then transformed into a matrix of emotional dissimilarity that was
      analyzed with multidimensional scaling methods (MDS). We compared the outcome of
      these analyses for the 25-s and 1-s duration conditions. In the second study, we
      presented musical excerpts of increasing duration, varying from 250 to 20
      seconds. Participants were requested to evaluate on a subjective scale how
      "moving" each excerpt was. On the basis of the responses given for the longer
      duration, excerpts were then sorted into two groups: highly moving and weakly (or
      less) moving. The main purpose of the analysis was to identify the point in time
      where these two categories of excerpts started to be differentiated by
      participants. Both studies provide consistent findings that less than 1 s of
      music is enough to instill elaborated emotional responses in listeners.

PMID- 16597798
TI  - Remember Bach: an investigation in episodic memory for music.
AB  - Emotional events are remembered better than nonemotional ones, especially after a
      long period of time. In this study, we investigated whether emotional music is
      kept better in episodic long-term memory than less emotional music and to which
      extent musical structure is important.

PMID- 16597799
TI  - Key processing precedes emotional categorization of Western music.
AB  - To investigate whether key processing precedes the appraisal of valence in music,
      participants listened to pairs of clips of same or different valence, played
      either in the same key or one semitone apart. They judged whether the second clip
      expressed the same emotion as the first one. Our predictions were confirmed: the
      response times obtained were shorter when both clips were played in the same key
      than when they were played one semitone apart.

PMID- 16597800
TI  - How does music arouse "chills"? Investigating strong emotions, combining
      psychological, physiological, and psychoacoustical methods.
AB  - Music can arouse ecstatic "chill" experiences defined as "goose pimples" and as
      "shivers down the spine." We recorded chills both via subjects' self-reports and
      physiological reactions, finding that they do not occur in a reflex-like manner,
      but as a result of attentive, experienced, and conscious musical enjoyment.

PMID- 16597801
TI  - Emotion processing of major, minor, and dissonant chords: a functional magnetic
      resonance imaging study.
AB  - Musicians and nonmusicians listened to major, minor, and dissonant musical chords
      while their BOLD brain responses were registered with functional magnetic
      resonance imaging. In both groups of listeners, minor and dissonant chords,
      compared with major chords, elicited enhanced responses in several brain areas,
      including the amygdala, retrosplenial cortex, brain stem, and cerebellum, during
      passive listening but not during memorization of the chords. The results indicate
      that (1) neural processing in emotion-related brain areas is activated even by
      single chords, (2) emotion processing is enhanced in the absence of cognitive
      requirements, and (3) musicians and nonmusicians do not differ in their neural
      responses to single musical chords during passive listening.

PMID- 16597802
TI  - Left auditory cortex specialization for vertical harmonic structure of chords.
AB  - The representation of consonant and dissonant chords in the auditory cortex was
      investigated using low-noise functional magnetic resonance imaging and different
      experimental paradigms to separate the effects of vertical harmony from those of
      other musical features. The results revealed higher activation by consonant
      compared with dissonant chords in the left posterior auditory cortex, suggesting
      contributions of mechanisms of encoding the acoustical chord structure rather
      than mechanisms based on sequential integration of chords.

PMID- 16597803
TI  - Emotional processing of harmonic expectancy violations.
AB  - This study is about whether harmonic expectancy violations can trigger emotional
      processes, as indexed by physiological and subjective measures.

PMID- 16597804
TI  - Dimensions of emotion in expressive musical performance.
AB  - This paper explores the dimensions of emotion conveyed by music. Participants
      rated emotion terms after seeing and/or hearing recordings of clarinet
      performances that varied in expressive content. A factor analysis revealed four
      independent dimensions of emotion. Changes to the clarinetists' expressive
      intentions did not significantly affect emotions conveyed by sound. It was
      largely through the visual modality that expressive intentions influenced the
      experience for observers.

PMID- 16597806
TI  - Patients, clinical practice, and the internet.

PMID- 16597808
TI  - Dismembering the ethical physician.
AB  - Physicians may experience ethical distress when they are caught in difficult
      clinical situations that demand ethical decision making, particularly when their
      preferred action may contravene the expectations of patients and established
      authorities. When principled and competent doctors succumb to patient wishes or
      establishment guidelines and participate in actions they perceive to be ethically
      inappropriate, or agree to refrain from interventions they believe to be in the
      best interests of patients, individual professional integrity may be diminished,
      and ethical reliability is potentially compromised. In a climate of ever
      proliferating ethical quandaries, it is essential for the medical community,
      health institutions, and governing bodies to pursue a judicious tension between
      the indispensable regulation of physicians necessary to maintain professional
      standards and preserve public safety, and the support for "freedom of conscience"
      that principled physicians require to practise medicine in keeping with their
      personal ethical orientation.

PMID- 16597809
TI  - Effects of ageing on smell and taste.
AB  - Disorders of taste and smell commonly present diagnostic dilemmas to the medical
      profession. This may be secondary to the lack of knowledge and understanding of
      these conditions. There seems to be a low level of interest in the disorders,
      when compared with disruption of the other senses such as sight and hearing.
      Nevertheless, impairment of these senses are common and may be life threatening,
      especially when they involve the elderly patient. The aetiology of the conditions
      is widespread, and extend beyond the content of this article. This article will
      relate only to how the ageing process may contribute to sensory dysfunction. It
      will focus on how the ageing process changes the normal anatomy and physiology of
      the senses, how this effects the person's quality of life, and the current
      management of these conditions.

PMID- 16597810
TI  - COX-2 inhibitors and the heart: are all coxibs the same?
AB  - The selective COX-2 inhibitors (coxibs) were originally developed to minimise the
      adverse effects of conventional non-steroidal anti-inflammatory drugs (NSAIDs)
      while maintaining the same analgesic and anti-inflammatory properties. Many large
      studies confirmed the improved gastric side effect profile of coxibs compared
      with non-selective NSAIDs; however, reports of increased cardiovascular morbidity
      and mortality followed, and the manufacturer Merck was forced to withdraw
      rofecoxib (Vioxx) from the market. Other coxibs have also either perished or had
      restrictions placed on their use. However, there seem to be significant
      differences between coxibs regarding their cardiovascular profiles, and the
      evidence for a class effect is dubious. In this paper, the current body of
      knowledge regarding the cardiovascular toxicities of coxibs is reviewed. The take
      home message for prescribing NSAIDs and those coxibs still on the market seems to
      be one of caution rather than contraindication, except in patients with
      significant cardiovascular risk factors.

PMID- 16597811
TI  - The patient with supine hypertension and orthostatic hypotension: a clinical
      dilemma.
AB  - Coexistent supine hypertension and orthostatic hypotension (SH-OH) pose a
      particular therapeutic dilemma, as treatment of one aspect of the condition may
      worsen the other. Studies of SH-OH are to be found by and large on patients with
      autonomic nervous disorders as well as patients with chronic arterial
      hypertension. In medical practice, however, the aetiologies and clinical
      presentation of the syndrome seem to be more varied. In the most typical cases
      the diagnosis is straightforward and the responsible mechanism evident. In those
      patients with mild or non-specific symptoms, the diagnosis is more demanding and
      the investigation may benefit from results of the tilt test, bedside autonomic
      tests as well as haemodynamic assessment. Discrete patterns of SH-OH may be
      recognisable. This review focuses on the management of the patient with
      coexistent SH-OH.

PMID- 16597812
TI  - Gall stones and chronic pancreatitis: the black box in between.
AB  - The relation between gall stones and chronic pancreatitis is uncertain; there are
      differing opinions on this issue. Firstly, gall stones are the most common reason
      for acute pancreatitis, but it cannot cause chronic pancreatitis. Secondly, a
      connection between gall stones and chronic inflammation of the pancreas might
      exist. Numerous studies or investigations have shown that changes associated with
      chronic pancreatitis are common in gallstone patients. Although it seems that
      gall stones might be a cause of chronic pancreatitis according to these findings,
      clinical and experimental studies are still needed for confirmation, and further
      studies are required to determine the mechanisms involved.

PMID- 16597814
TI  - Recognition of acute illness in people with chronic neurological disability.
AB  - Coincidental acute illness is common in patients with chronic progressive or
      stable neurological disability. Although the presentation of acute illness in
      these patients is often similar to that in people without pre-existing
      disability, sometimes it may be atypical. In addition, an adequate medical
      history is often difficult to obtain in patients with advanced neurological
      disease, for example because of the presence of aphasia, severe dysarthria, or
      cognitive impairment. In these circumstances early and accurate diagnosis of
      acute medical and surgical emergencies requires both clinical acumen and a high
      index of suspicion. The aim of this article is to describe the main atypical
      manifestations of acute illness in patients with chronic disabling neurological
      disorders.

PMID- 16597815
TI  - Management of inflammatory bowel diseases in Eastern Europe.
AB  - Limited data are available on the management of inflammatory bowel diseases (IBD)
      in East European countries. The diagnostic tools and most treatment options are
      also available in Eastern Europe. The diagnostic procedures commonly used became
      more sophisticated in the past few years, with a greater use of computed
      tomography/magnetic resonance imaging and serology testing; however, double
      contrast barium enema, enteroclysis, and endoscopy remained standard. The medical
      therapy and surgical strategies are also somewhat different from those applied in
      Western countries. In ulcerative colitis, besides mesalazine, the use of
      sulphasalazine is still frequent, while azathioprine is only used in a minority
      of patients. The use of conventional corticosteroids is common and the rate of
      non-colorectal cancer associated colectomies is low. In contrast, 5
      aminosalicylates are still used for maintenance in Crohn's disease and
      azathioprine is generally less frequently given compared with Western Europe.
      Biological agents have also become available about five years ago, yet their use
      is restricted mainly to specialised centres.

PMID- 16597813
TI  - Aetiology, diagnosis, and management of hypopituitarism in adult life.
AB  - Hypopituitarism is a complex medical condition associated with increased
      morbidity and mortality, requires complicated treatment regimens, and
      necessitates lifelong follow up by the endocrinologist. The causes, clinical
      features, and the management of hypopituitarism including endocrine replacement
      therapy are considered in this review article.

PMID- 16597816
TI  - Assessment of internet use and effects among healthcare professionals: a cross
      sectional survey.
AB  - PURPOSE: Several studies have explored the scientific platforms on patient use of
      the internet for health information. In contrast physicians' perspective on
      evolving internet environment is lacking. The purpose of this study is to assess
      and correlate the extent of internet use among healthcare professionals and
      examine its effects on clinical practice. METHODS: Cross sectional survey
      conducted in the USA using questionnaires distributed randomly to healthcare
      professionals attending distinct continuing medical education programmes between
      2003 and 2004. Multiple choice and yes/no questions related to the trends of
      internet use and its effects on clinical practice were extracted and responses
      analysed. The main outcome measures are self reported rates of internet use,
      perceived effects, and the role of medical web sites in clinical practice.
      RESULTS: The overall response rate was 60%. A total of 277 survey respondents
      (97%) had internet access. Some 7% in private practice and 1% of group practice
      physicians did not have internet access. Most (71%) used the internet regularly
      for medical or professional updating and 62% (n = 178) felt the need for sharing
      web sites designed for healthcare professionals with patients. Some 27% of the
      physicians currently own established personal practice web sites. Sixty three per
      cent have recommended a web site to a patient for more information, matching the
      positive trust (>70%) on the general quality of selected medical web sites.
      CONCLUSION: This cross sectional survey shows that internet use and web based
      medical information is widely popular among physicians and patients. About 23%
      31% of the healthcare professionals report >80% interaction with web informed
      patients in their daily practice.

PMID- 16597818
TI  - Practical experience of using directly observed procedures, mini clinical
      evaluation examinations, and peer observation in pre-registration house officer
      (FY1) trainees.
AB  - This paper describes an eight month experience with three of the four main
      assessment tools that will be used to validate the successful completion of the
      FY1 placement. The practical issues around the implementation of these new tools
      is of great concern to all involved in the management of postgraduate training
      and it is hoped that this paper will contribute some of the practical elements so
      far unavailable from Department of Health sources.

PMID- 16597817
TI  - Prevalence of obesity in type 2 diabetes in secondary care: association with
      cardiovascular risk factors.
AB  - AIMS: To determine the prevalence of overweight and obesity among patients with
      type 1 and type 2 diabetes mellitus attending a secondary care diabetes clinic in
      the United Kingdom, and to assess the impact of overweight and obesity on
      glycaemic control and cardiovascular risk factors in patients with type 2
      diabetes. METHODS: 3637 patients with diabetes were identified from the hospital
      electronic diabetes register, 916 with type 1 diabetes (mean (SD) age 40.4 (15.1)
      years, 496 male) and 2721 with type 2 diabetes (mean (SD) age 62.5 (11.8) years,
      1436 male). Data on body mass index (BMI), glycaemic control, lipid profiles, and
      blood pressure were extracted. RESULTS: Of patients with type 1 diabetes, 55.3%
      were overweight (BMI >or=25 kg/m(2)), 16.6% were obese (BMI >or=30 kg/m(2)), and
      0.4% had morbid obesity (BMI >or=40 kg/m(2)). In contrast, 86% of patients with
      type 2 diabetes were overweight or obese, 52% were obese, and 8.1% had morbid
      obesity. Obese patients with type 2 diabetes were younger, had poorer glycaemic
      control, higher blood pressures, worse lipid profiles, and were more likely to be
      receiving antihypertensive and lipid lowering drugs compared with patients with
      BMI <30 kg/m(2). CONCLUSIONS: Obesity is the rule among patients attending this
      hospital diabetes clinic, with 86% of those with type 2 diabetes overweight or
      obese. Obesity is associated with significantly worse cardiovascular risk factors
      in this patient group, suggesting that more active interventions to control
      weight gain would be appropriate.

PMID- 16597819
TI  - Diffusion weighted magnetic resonance imaging for acute stroke: practical and
      popular.
AB  - AIM: To evaluate the feasibility and impact of diffusion weighted magnetic
      resonance imaging (DW MRI) as the first line neuroimaging of stroke at a district
      general hospital. METHODS: Prospective audit of all in-patients admitted with
      clinically suspected acute stroke and referred for imaging over a consecutive 17
      week period. The data collected included scan type, time from cerebral event to
      imaging request, and time from formal radiological request to neuroimaging.
      Clinicians' (general physicians, neurologists, and radiologists) perceptions were
      assessed by a questionnaire. RESULTS: 148 patients had neuroimaging for
      clinically suspected stroke during this period. Eighty one per cent of patients
      (120 of 148) had DW MRI as first line. Ninety two per cent of these patients had
      DW MRI within 24 hours of the formal radiological request. Twenty eight patients
      did not undergo DW MRI because lack of MRI safety, clinical state, unavailability
      because of maintenance service or lack of trained staff. Clinicians found the
      introduction of the DW MRI based service a significant improvement on computed
      tomography, especially for equivocal cases. CONCLUSION: DW based MRI service is
      both feasible and sustainable in the setting of a district general hospital and
      most clinicians feel that this is a significant improvement to stroke services.

PMID- 16597820
TI  - Solution structure of the antifreeze-like domain of human sialic acid synthase.
AB  - The structure of the C-terminal antifreeze-like (AFL) domain of human sialic acid
      synthase was determined by NMR spectroscopy. The structure comprises one alpha-
      and two single-turn 3(10)-helices and two beta-strands, and is similar to those
      of the type III antifreeze proteins. Evolutionary trace analyses of the type III
      antifreeze protein family suggested that the class-specific residues in the human
      and bacterial AFL domains are important for their substrate binding, while the
      class-specific residues of the fish antifreeze proteins are gathered on the ice
      binding surface.

PMID- 16597821
TI  - Secondary structure and dynamics of micelle bound beta- and gamma-synuclein.
AB  - We have used solution state NMR spectroscopy to characterize the secondary
      structure and backbone dynamics of the proteins beta- and gamma-synuclein in
      their detergent micelle-bound conformations. Comparison of the results with those
      previously obtained for the Parkinson's disease-linked protein alpha-synuclein
      shows that structural differences between the three homologous synuclein family
      members are directly related to variations in their primary amino acid sequences.
      An 11-residue deletion in the lipid-binding domain of beta-synuclein leads to the
      destabilization of an entire segment of the micelle-bound helical structure
      containing the deletion site. The acidic C-terminal tail region of gamma
      synuclein, which displays extensive sequence divergence, is more highly
      disordered than the corresponding regions in the other two family members. The
      observed structural differences are likely to mediate functional variations
      between the three proteins, with differences between alpha- and beta-synuclein
      expected to revolve around their lipid interactions, while differences in gamma
      synuclein function are expected to result from different protein-protein
      interactions mediated by its unique C-terminal tail.

PMID- 16597822
TI  - pK values of the ionizable groups of proteins.
AB  - We have used potentiometric titrations to measure the pK values of the ionizable
      groups of proteins in alanine pentapeptides with appropriately blocked termini.
      These pentapeptides provide an improved model for the pK values of the ionizable
      groups in proteins. Our pK values determined in 0.1 M KCl at 25 degrees C are:
      3.67+/-0.03 (alpha-carboxyl), 3.67+/-0.04 (Asp), 4.25+/-0.05 (Glu), 6.54+/-0.04
      (His), 8.00+/-0.03 (alpha-amino), 8.55+/-0.03 (Cys), 9.84+/-0.11 (Tyr), and
      10.40+/-0.08 (Lys). The pK values of some groups differ from the Nozaki and
      Tanford (N & T) pK values often used in the literature: Asp (3.67 this work vs.
      4.0 N & T); His (6.54 this work vs. 6.3 N & T); alpha-amino (8.00 this work vs.
      7.5 N & T); Cys (8.55 this work vs. 9.5 N & T); and Tyr (9.84 this work vs. 9.6 N
      & T). Our pK values will be useful to those who study pK perturbations in folded
      and unfolded proteins, and to those who use theory to gain a better understanding
      of the factors that determine the pK values of the ionizable groups of proteins.

PMID- 16597823
TI  - The IclR family of transcriptional activators and repressors can be defined by a
      single profile.
AB  - In the last decade enormous advances in life sciences have been possible due to
      the information obtained from DNA sequencing projects. The optimal interpretation
      and analysis of genome sequence data requires the precise annotation and
      classification of proteins deduced from open reading frames, which is usually
      done with the help of family-specific signatures. Here we report a novel profile
      for the IclR type of transcriptional activators and repressors. In contrast to
      profiles for other families of transcriptional regulators, the new IclR profile
      is located outside the helix-turn-helix DNA-binding motif. We provide evidence
      that the new profile is more specific than any of the existing signatures for
      this family of regulators. More than 500 representatives of this family were
      identified with this profile. A database on bacterial regulators
      (http://www.bactregulators.org) was built to compile and regroup the sequences
      with the aid of the new profile.

PMID- 16597824
TI  - Expression, purification, and characterization of Thermotoga maritima membrane
      proteins for structure determination.
AB  - Structural studies of integral membrane proteins typically rely upon detergent
      micelles as faithful mimics of the native lipid bilayer. Therefore, membrane
      protein structure determination would be greatly facilitated by biophysical
      techniques that are capable of evaluating and assessing the fold and oligomeric
      state of these proteins solubilized in detergent micelles. In this study, an
      approach to the characterization of detergent-solubilized integral membrane
      proteins is presented. Eight Thermotoga maritima membrane proteins were screened
      for solubility in 11 detergents, and the resulting soluble protein-detergent
      complexes were characterized with small angle X-ray scattering (SAXS), nuclear
      magnetic resonance (NMR) spectroscopy, circular dichroism (CD) spectroscopy, and
      chemical cross-linking to evaluate the homogeneity, oligomeric state, radius of
      gyration, and overall fold. A new application of SAXS is presented, which does
      not require density matching, and NMR methods, typically used to evaluate soluble
      proteins, are successfully applied to detergent-solubilized membrane proteins.
      Although detergents with longer alkyl chains solubilized the most proteins,
      further characterization indicates that some of these protein-detergent complexes
      are not well suited for NMR structure determination due to conformational
      exchange and protein oligomerization. These results emphasize the need to screen
      several different detergents and to characterize the protein-detergent complex in
      order to pursue structural studies. Finally, the physical characterization of the
      protein-detergent complexes indicates optimal solution conditions for further
      structural studies for three of the eight overexpressed membrane proteins.

PMID- 16597826
TI  - Secondary structure, orientation, and oligomerization of phospholemman, a cardiac
      transmembrane protein.
AB  - Human phospholemman (PLM) is a 72-residue protein, which is expressed at high
      density in the cardiac plasma membrane and in various other tissues. It forms ion
      channels selective for K+, Cl-, and taurine in lipid bilayers and colocalizes
      with the Na+/K+-ATPase and the Na+/Ca2+-exchanger, which may suggest a role in
      the regulation of cell volume. Here we present the first structural data based on
      synthetic peptides representing the transmembrane domain of PLM. Perfluoro
      octaneoate-PAGE of reconstituted proteoliposomes containing PLM reveals a
      tetrameric homo-oligomerization. Infrared spectroscopy of proteoliposomes shows
      that the PLM peptide is completely alpha-helical, even beyond the hydrophobic
      core residues. Hydrogen/deuterium exchange experiments reveal that a core of 20
      22 residues is not accessible to water, thus embedded in the lipid membrane. The
      maximum helix tilt is 17 degrees +/- 2 degrees obtained by attenuated total
      reflection infrared spectroscopy. Thus, our data support the idea of ion channel
      formation by the PLM transmembrane domain.

PMID- 16597825
TI  - Inhibition of insulin fibrillogenesis with targeted peptides.
AB  - Under conditions of acidic pH and elevated temperature, insulin partially unfolds
      and aggregates into highly structured amyloid fibrils. Aggregation of insulin
      leads to loss of activity and can trigger an unwanted immune response. Compounds
      that prevent protein aggregation have been used to stabilize insulin; these
      compounds generally suppress aggregation only at relatively high inhibitor
      concentrations. For example, effective inhibition of aggregation of 0.5 mM
      insulin required arginine concentrations of > or =100 mM. Here, we investigate a
      targeted approach toward inhibiting insulin aggregation. VEALYL, corresponding to
      residues B12-17 of full-length insulin, was identified as a short peptide that
      interacts with full-length insulin. A hybrid peptide was synthesized that
      contained this binding domain and hexameric arginine; this peptide significantly
      reduced the rate of insulin aggregation at near-equimolar concentrations. An
      effective binding domain and N-terminal placement of the arginine hexamer were
      necessary for inhibitory activity. The data were analyzed using a simple two-step
      model of aggregation kinetics. These results are useful not only in identifying
      an insulin aggregation inhibitor but also in extending a targeted protein
      strategy for modifying aggregation of amyloidogenic proteins.

PMID- 16597828
TI  - Src kinase activation: A switched electrostatic network.
AB  - Src tyrosine kinases are essential in numerous cell signaling pathways, and
      improper functioning of these enzymes has been implicated in many diseases. The
      activity of Src kinases is regulated by conformational activation, which involves
      several structural changes within the catalytic domain (CD): the orientation of
      two lobes of CD; rearrangement of the activation loop (A-loop); and movement of
      an alpha-helix (alphaC), which is located at the interface between the two lobes,
      into or away from the catalytic cleft. Conformational activation was investigated
      using biased molecular dynamics to explore the transition pathway between the
      active and the down-regulated conformation of CD for the Src-kinase family member
      Lyn kinase, and to gain insight into the interdependence of these changes. Lobe
      opening is observed to be a facile motion, whereas movement of the A-loop motion
      is more complex requiring secondary structure changes as well as communication
      with alphaC. A key result is that the conformational transition involves a switch
      in an electrostatic network of six polar residues between the active and the down
      regulated conformations. The exchange between interactions links the three main
      motions of the CD. Kinetic experiments that would demonstrate the contribution of
      the switched electrostatic network to the enzyme mechanism are proposed. Possible
      implications for regulation conferred by interdomain interactions are also
      discussed.

PMID- 16597827
TI  - Solution structure of Asl1650, an acyl carrier protein from Anabaena sp. PCC 7120
      with a variant phosphopantetheinylation-site sequence.
AB  - Cyanobacteria, such as Anabaena, produce a variety of bioactive natural products
      via polyketide synthases (PKS), nonribosomal peptide synthetases (NRPS), and
      hybrid peptide/polyketide pathways. The protein Asl1650, which is a member of the
      acyl carrier protein family from the cyanobacterium Anabaena sp. PCC 7120, is
      encoded in a region of the Anabaena genome that is rich in PKS and NRPS genes. To
      gain new insight into the physiological role of acyl carriers in Anabaena, the
      solution structure of Asl1650 has been solved by NMR spectroscopy. The protein
      adopts a twisted antiparallel four-helix bundle fold, with a variant
      phosphopantetheine-attachment motif positioned at the start of the second helix.
      Structure comparisons with proteins from other organisms suggest a likely
      physiological function as a discrete peptidyl carrier protein.

PMID- 16597829
TI  - Modulation of protein aggregation by polyethylene glycol conjugation: GCSF as a
      case study.
AB  - Polyethylene glycol (PEG) conjugation to proteins has emerged as an important
      technology to produce drug molecules with sustained duration in the body.
      However, the implications of PEG conjugation to protein aggregation have not been
      well understood. In this study, conducted under physiological pH and temperature,
      N-terminal attachment of a 20 kDa PEG moiety to GCSF had the ability to (1)
      prevent protein precipitation by rendering the aggregates soluble, and (2) slow
      the rate of aggregation relative to GCSF. Our data suggest that PEG-GCSF
      solubility was mediated by favorable solvation of water molecules around the PEG
      group. PEG-GCSF appeared to aggregate on the same pathway as that of GCSF, as
      evidenced by (a) almost identical secondary structural transitions accompanying
      aggregation, (b) almost identical covalent character in the aggregates, and (c)
      the ability of PEG-GCSF to rescue GCSF precipitation. To understand the role of
      PEG length, the aggregation properties of free GCSF were compared to 5kPEG-GCSF
      and 20kPEG-GCSF. It was observed that even 5kPEG-GCSF avoided precipitation by
      forming soluble aggregates, and the stability toward aggregation was vastly
      improved compared to GCSF, but only marginally less stable than the 20kPEG-GCSF.
      Biological activity measurements demonstrated that both 5kPEG-GCSF and 20kPEG
      GCSF retained greater activity after incubation at physiological conditions than
      free GCSF, consistent with the stability measurements. The data is most
      compatible with a model where PEG conjugation preserves the mechanism underlying
      protein aggregation in GCSF, steric hindrance by PEG influences aggregation rate,
      while aqueous solubility is mediated by polar PEG groups on the aggregate
      surface.

PMID- 16597830
TI  - Sequential reorganization of beta-sheet topology by insertion of a single strand.
AB  - Insertions, duplications, and deletions of sequence segments are thought to be
      major evolutionary mechanisms that increase the structural and functional
      diversity of proteins. Alternative splicing, for example, is an intracellular
      editing mechanism that is thought to generate isoforms for 30%-50% of all human
      genes. Whereas the inserted sequences usually display only minor structural
      rearrangements at the insertion site, recent observations indicate that they may
      also cause more dramatic structural displacements of adjacent structures. In the
      present study we test how artificially inserted sequences change the structure of
      the beta-sheet region in T4 lysozyme. Copies of two different beta-strands were
      inserted into two different loops of the beta-sheet, and the structures were
      determined. Not surprisingly, one insert "loops out" at its insertion site and
      forms a new small beta-hairpin structure. Unexpectedly, however, the second
      insertion leads to displacement of adjacent strands and a sequential
      reorganization of the beta-sheet topology. Even though the insertions were
      performed at two different sites, looping out occurred at the C-terminal end of
      the same beta-strand. Reasons as to why a non-native sequence would be recruited
      to replace that which occurs in the native protein are discussed. Our results
      illustrate how sequence insertions can facilitate protein evolution through both
      local and nonlocal changes in structure.

PMID- 16597831
TI  - Affinity enhancement of an in vivo matured therapeutic antibody using structure
      based computational design.
AB  - Improving the affinity of a high-affinity protein-protein interaction is a
      challenging problem that has practical applications in the development of
      therapeutic biomolecules. We used a combination of structure-based computational
      methods to optimize the binding affinity of an antibody fragment to the I-domain
      of the integrin VLA1. Despite the already high affinity of the antibody (Kd
      approximately 7 nM) and the moderate resolution (2.8 A) of the starting crystal
      structure, the affinity was increased by an order of magnitude primarily through
      a decrease in the dissociation rate. We determined the crystal structure of a
      high-affinity quadruple mutant complex at 2.2 A. The structure shows that the
      design makes the predicted contacts. Structural evidence and mutagenesis
      experiments that probe a hydrogen bond network illustrate the importance of
      satisfying hydrogen bonding requirements while seeking higher-affinity mutations.
      The large and diverse set of interface mutations allowed refinement of the mutant
      binding affinity prediction protocol and improvement of the single-mutant success
      rate. Our results indicate that structure-based computational design can be
      successfully applied to further improve the binding of high-affinity antibodies.

PMID- 16597832
TI  - Structure and dynamics of the epidermal growth factor receptor C-terminal
      phosphorylation domain.
AB  - The C-terminal phosphorylation domain of the epidermal growth factor receptor is
      believed to regulate protein kinase activity as well as mediate the assembly of
      signal transduction complexes. The structure and dynamics of this proposed
      autoregulatory domain were examined by labeling the extreme C terminus of the
      EGFR intracellular domain (ICD) with an extrinsic fluorophore. Fluorescence
      anisotropy decay analysis of the nonphosphorylated EGFR-ICD yielded two
      rotational correlation times: a longer time, consistent with the global
      rotational motion of a 60- to 70-kDa protein with an elongated globular
      conformation, and a shorter time, presumably contributed by segmental motion near
      the fluorophore. A C-terminally truncated form of EGFR-ICD yielded a slow
      component consistent with the rotational motion of the 38-kDa kinase core. These
      findings suggested a structural arrangement of the EGFR-ICD in which the C
      terminal phosphorylation domain interacts with the kinase core to move as an
      extended structure. A marked reduction in the larger correlation time of EGFR-ICD
      was observed upon its autophosphorylation. This dynamic component was faster than
      predicted for the globular motion of the 62-kDa EGFR-ICD, suggesting an increase
      in the mobility of the C-terminal domain and a likely displacement of this domain
      from the kinase core. The interaction between the SH2 domain of c-Src and the
      phosphorylated EGFR C-terminal domain was shown to impede its mobility. Circular
      dichroism spectroscopy indicated that the EGFR C-terminal domain possessed a
      significant level of secondary structure in the form of alpha-helices and beta
      sheets, with a marginal change in beta-sheet content occurring upon
      phosphorylation.

PMID- 16597833
TI  - The contribution of the residues from the main hydrophobic core of ribonuclease A
      to its pressure-folding transition state.
AB  - The role of hydrophobic interactions established by the residues that belong to
      the main hydrophobic core of ribonuclease A in its pressure-folding transition
      state was investigated using the Phi-value method. The folding kinetics was
      studied using pressure-jump techniques both in the pressurization and
      depressurization directions. The ratio between the folding activation volume and
      the reaction volume (beta p-value), which is an index of the compactness or
      degree of solvation of the transition state, was calculated. All the positions
      analyzed presented fractional Phi f-values, and the lowest were those
      corresponding to the most critical positions for the ribonuclease A stability.
      The structure of the transition state of the hydrophobic core of ribonuclease A,
      from the point of view of formed interactions, is a relatively, uniformly
      expanded form of the folded structure with a mean Phi f-value of 0.43. This
      places it halfway between the folded and unfolded states. On the other hand, for
      the variants, the average of beta p-values is 0.4, suggesting a transition state
      that is 40% native-like. Altogether the results suggest that the pressure-folding
      transition state of ribonuclease A looks like a collapsed globule with some
      secondary structure and a weakened hydrophobic core. A good correlation was found
      between the Phi f-values and the Deltabeta p-values. Although the nature of the
      transition state inferred from pressure-induced folding studies and the results
      of the protein engineering method have been reported to be consistent for other
      proteins, to the best of our knowledge this is the first direct comparison using
      a set of mutants.

PMID- 16597834
TI  - Calorimetric and structural studies of the nitric oxide carrier S
      nitrosoglutathione bound to human glutathione transferase P1-1.
AB  - The nitric oxide molecule (NO) is involved in many important physiological
      processes and seems to be stabilized by reduced thiol species, such as S
      nitrosoglutathione (GSNO). GSNO binds strongly to glutathione transferases, a
      major superfamily of detoxifying enzymes. We have determined the crystal
      structure of GSNO bound to dimeric human glutathione transferase P1-1 (hGSTP1-1)
      at 1.4 A resolution. The GSNO ligand binds in the active site with the nitrosyl
      moiety involved in multiple interactions with the protein. Isothermal titration
      calorimetry and differential scanning calorimetry (DSC) have been used to
      characterize the interaction of GSNO with the enzyme. The binding of GSNO to wild
      type hGSTP1-1 induces a negative cooperativity with a kinetic process concomitant
      to the binding process occurring at more physiological temperatures. GSNO
      inhibits wild-type enzyme competitively at lower temperatures but covalently at
      higher temperatures, presumably by S-nitrosylation of a sulfhydryl group. The
      C47S mutation removes the covalent modification potential of the enzyme by GSNO.
      These results are consistent with a model in which the flexible helix alpha2 of
      hGST P1-1 must move sufficiently to allow chemical modification of Cys47. In
      contrast to wild-type enzyme, the C47S mutation induces a positive cooperativity
      toward GSNO binding. The DSC results show that the thermal stability of the
      mutant is slightly higher than wild type, consistent with helix alpha2 forming
      new interactions with the other subunit. All these results suggest that Cys47
      plays a key role in intersubunit cooperativity and that under certain
      pathological conditions S-nitrosylation of Cys47 by GSNO is a likely
      physiological scenario.

PMID- 16597835
TI  - Modular organization of FDH: Exploring the basis of hydrolase catalysis.
AB  - An abundant enzyme of liver cytosol, 10-formyltetrahydrofolate dehydrogenase
      (FDH), is an interesting example of a multidomain protein. It consists of two
      functionally unrelated domains, an aldehyde dehydrogenase-homologous domain and a
      folate-binding hydrolase domain, which are connected by an approximately 100
      residue linker. The amino-terminal hydrolase domain of FDH (Nt-FDH) is a homolog
      of formyl transferase enzymes that utilize 10-formyl-THF as a formyl donor.
      Interestingly, the concerted action of all three domains of FDH produces a new
      catalytic activity, NADP+-dependent oxidation of 10-formyltetrahydrofolate (10
      formyl-THF) to THF and CO2. The present studies had two objectives: First, to
      explore the modular organization of FDH through the production of hybrid enzymes
      by domain replacement with methionyl-tRNA formyltransferase (FMT), an enzyme
      homologous to the hydrolase domain of FDH. The second was to explore the
      molecular basis for the distinct catalytic mechanisms of Nt-FDH and related 10
      formyl-THF utilizing enzymes. Our studies revealed that FMT cannot substitute for
      the hydrolase domain of FDH in order to catalyze the dehydrogenase reaction. It
      is apparently due to inability of FMT to catalyze the hydrolysis of 10-formyl-THF
      in the absence of the cosubstrate of the transferase reaction despite the high
      similarity of the catalytic centers of the two enzymes. Our results further imply
      that Ile in place of Asn in the FDH hydrolase catalytic center is an important
      determinant for hydrolase catalysis as opposed to transferase catalysis.

PMID- 16597837
TI  - The C-terminal domain of the transcriptional corepressor CtBP is intrinsically
      unstructured.
AB  - C-terminal binding proteins (CtBPs) are moonlighting proteins involved in nuclear
      transcriptional corepression and in Golgi membrane tubule fission. Structural
      information on CtBPs is available for their substrate-binding domain, responsible
      for transcriptional repressor recognition/binding, and for the nucleotide-binding
      domain, involved in NAD(H)-binding and dimerization. On the contrary, little is
      known about the structure of CtBP C-terminal region ( approximately 90 residues),
      hosting sites for post-translational modifications. In the present communication
      we apply a combined approach based on bioinformatics, nuclear magnetic resonance,
      circular dichroism spectroscopy, and small-angle X-ray scattering, and we show
      that the CtBP C-terminal region is intrinsically unstructured in the full-length
      CtBP and in constructs lacking the substrate- and/or the nucleotide-binding
      domains. The flexible nature of this protein region, and its structural
      transitions, may be instrumental for CtBP recognition and binding to diverse
      molecular partners.

PMID- 16597838
TI  - Crystal structure of the conserved protein TTHA0727 from Thermus thermophilus HB8
      at 1.9 A resolution: A CMD family member distinct from carboxymuconolactone
      decarboxylase (CMD) and AhpD.
AB  - TTHA0727 is a conserved hypothetical protein from Thermus thermophilus HB8, with
      a molecular mass of 12.6 kDa. TTHA0727 belongs to the carboxymuconolactone
      decarboxylase (CMD) family (Pfam 02627). A sequence comparison with its homologs
      suggested that TTHA0727 is a distinct protein from alkylhydroperoxidase AhpD and
      gamma-carboxymuconolactone decarboxylase in the CMD family. Here we report the
      1.9 A crystal structure of TTHA0727 (PDB ID: 2CWQ) determined by the
      multiwavelength anomalous dispersion method. The TTHA0727 monomer structure
      consists of seven alpha-helices (alpha1-alpha7) and one short 3(10)-helix. The
      crystal structure and the analytical ultracentrifugation revealed that TTHA0727
      forms a hexameric ring structure in solution. The electrostatic potential
      distribution on the solvent-accessible surface of the TTHA0727 hexamer showed
      that positively charged regions exist on the side of the ring structure,
      suggesting that TTHA0727 interacts with some negatively charged molecules. A
      structural homology search revealed that the structure of three alpha-helices
      (alpha4-alpha6) is remarkably conserved, suggesting that it is the common
      structural motif for the CMD family proteins. In addition, the nine residues of
      the N-terminal tag bound to the cleft region between alpha1 and alpha3 in chains
      A and B of TTHA0727, implying that this region is the putative binding/active
      site for some small molecules.

PMID- 16597836
TI  - Enhancing functional production of G protein-coupled receptors in Pichia pastoris
      to levels required for structural studies via a single expression screen.
AB  - We have optimized the expression level of 20 mammalian G protein-coupled
      receptors (GPCRs) in the methylotrophic yeast Pichia pastoris. We found that
      altering expression parameters, including growth temperature, and supplementation
      of the culture medium with specific GPCR ligands, histidine, and DMSO increased
      the amount of functional receptor, as assessed by ligand binding, by more than
      eightfold over standard expression conditions. Unexpectedly, we found that the
      overall amount of GPCR proteins expressed, in most cases, varied only marginally
      between standard and optimized expression conditions. Accordingly, the optimized
      expression conditions resulted in a marked fractional increase in the ratio of
      ligand binding-competent receptor to total expressed receptor. The results of
      this study suggest a general approach for increasing yields of functional
      mammalian GPCRs severalfold over standard expression conditions by using a set of
      optimized expression condition parameters that we have characterized for the
      Pichia expression system. Overall, we have more than doubled the number of GPCR
      targets that can be produced in our laboratories in sufficient amounts for
      structural studies.

PMID- 16597839
TI  - Agonist-induced cell surface trafficking of an intracellularly sequestered D1
      dopamine receptor homo-oligomer.
AB  - The role of oligomerization in D1 dopamine receptor trafficking to the cell
      surface was examined using conformationally distinct variants of this receptor.
      Substitution of the highly conserved aspartic acid (Asp103) in transmembrane
      domain 3 resulted in a constitutively active receptor, D103A, that did not bind
      agonists or antagonists but trafficked to the cell surface as oligomers.
      Coexpression of D103A with the wild-type D1 receptor in human embryonic kidney
      293t cells resulted in inhibition of cell surface expression of the D1 receptor
      because of receptor oligomerization, causing intracellular retention of both
      proteins. Rescue of the intracellularly retained oligomer could be achieved only
      by membrane-permeable full and partial agonists, which resulted in cell surface
      expression of the D1 receptor, whereas cell-permeable antagonists and cell
      impermeable agonists had no effect. Cell surface fluorescence resonance energy
      transfer studies of cells coexpressing D103A and D1 revealed no signal before
      agonist treatment but a robust signal after agonist treatment, indicating that
      the intact D1/D103A oligomer reached the cell surface only after agonist
      treatment but not under basal conditions. This suggests that rescue of the
      retained D1/D103A oligomer to the cell surface was a result of an agonist-induced
      change in the conformation of D1, permitting cell surface trafficking of the
      D1/D103A receptor oligomeric complex from the endoplasmic reticulum.

PMID- 16597840
TI  - Use of semiconductor-based oligonucleotide microarrays for influenza a virus
      subtype identification and sequencing.
AB  - In the face of concerns over an influenza pandemic, identification of virulent
      influenza A virus isolates must be obtained quickly for effective responses.
      Rapid subtype identification, however, is difficult even in well-equipped
      virology laboratories or is unobtainable in the field under more austere
      conditions. Here we describe a genome assay and microarray design that can be
      used to rapidly identify influenza A virus hemagglutinin subtypes 1 through 15
      and neuraminidase subtypes 1 through 9. Also described is an array-based
      enzymatic assay that can be used to sequence portions of both genes or any other
      sequence of interest.

PMID- 16597841
TI  - Evaluation of the IDI-MRSA assay for detection of methicillin-resistant
      staphylococcus aureus from nasal and rectal specimens pooled in a selective
      broth.
AB  - Rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) by PCR can
      be performed directly from nasal specimens with the IDI-MRSA assay. To improve
      the efficiency of screening, we evaluated the performance of the IDI-MRSA assay
      for the detection of MRSA from pooled and unpooled specimens cultured in a
      selective broth. Of the 287 specimens evaluated, 71 were culture and PCR
      positive, 203 were culture and PCR negative, 3 were culture positive and PCR
      negative, 8 were culture negative and PCR positive, and 2 remained inhibited. A
      methicillin-susceptible Staphylococcus aureus isolate was recovered from five of
      the eight specimens with false-positive PCR results. Compared to the results of
      culture, the sensitivity, specificity, and positive and negative [corrected]
      predictive values of the IDI-MRSA assay for detection of MRSA from broth were
      96%, 96%, 90%, and 98%, respectively. Following implementation of the IDI-MRSA
      assay, PCR-positive broths were subcultured for evaluation of assay performance.
      Of the 298 IDI-MRSA assay-positive broths, the results for 103 could not be
      confirmed by culture. A methicillin-susceptible S. aureus (MSSA) isolate was
      recovered from 77 of these 103 broths. Repeat testing by the IDI-MRSA assay
      directly with the MSSA isolates confirmed the original positive PCR result. The
      positive predictive value of the IDI-MRSA assay fell from 90% during the
      evaluation phase to 65% postimplementation. The IDI-MRSA assay performed well for
      the detection of MRSA from a selective broth compared to the performance of the
      detection of MRSA from culture. However, because of the burden associated with
      implementation of infection control precautions, cultures remain essential in
      confirming positive IDI-MRSA results.

PMID- 16597842
TI  - Potential impact of conjugate vaccine on the incidence of invasive pneumococcal
      disease among children in Scotland.
AB  - We sought to determine the potential impact of seven-valent pneumococcal
      conjugate vaccine on the incidence of invasive pneumococcal disease (IPD) among
      children in Scotland. Invasive pneumococci from blood and cerebrospinal fluid,
      isolated between 2000 and 2004 from all children aged less than 5 years in
      Scotland, were characterized by serotyping. Using reported efficacy data of the
      seven-valent pneumococcal conjugate vaccine (PCV7) along with likely coverage
      rates, we made an estimation of the potential impact on the incidence of IPD
      among children in Scotland. A total of 217 pneumococci were characterized into 22
      different serogroups/types, the most common, in rank order, being 14, 19F, 6B,
      18C, 23F, 9V, 4, 1, 19A, and 6A. Estimated serotype coverage for PCV7 was 76.5%
      in those aged less than 5 years of age but increased to 88.9% for those aged 1
      year. By using serotype coverage and estimates of vaccine efficacy and uptake,
      the potential impact of the vaccine for those greater than 2 months of age, but
      less than 5 years, was estimated as 67.3%, leading to an average of 29
      preventable cases per year. The introduction of PCV7 into the childhood
      immunization schedule would reduce the burden of pneumococcal disease in
      children, and the incidence would be particularly reduced in those children aged
      1 year. Additional benefits may be gained in adults through herd protection.
      Continued surveillance of IPD is required before, during, and after the
      introduction of PCV7.

PMID- 16597843
TI  - Sequence variation in the T-cell epitopes of the Plasmodium falciparum
      circumsporozoite protein among field isolates is temporally stable: a 5-year
      longitudinal study in southern Vietnam.
AB  - In an effort to decipher the nature and extent of antigen polymorphisms of
      malaria parasites in a setting where malaria is hypomesoendemic, we conducted a 5
      year longitudinal study (1998 to 2003) by sequencing the Th2R and Th3R epitopes
      of the circumsporozoite protein (CSP) of 142 Plasmodium falciparum field isolates
      from Bao Loc, Vietnam. Samples were collected during the high-transmission
      season, September through December 1998 (n = 43), as well as from July 2000 to
      August 2001 (n = 34), September 2001 to July 2002 (n = 33), and August 2002 to
      July 2003 (n = 32). Marked sequence diversity was noted during the high
      transmission season in 1998, but no significant variation in allele frequencies
      was observed over the years (chi(2) = 70.003, degrees of freedom = 57, P =
      0.116). The apparent temporal stability in allele frequency observed in this Bao
      Loc malaria setting may suggest that polymorphism in the Th2R and Th3R epitopes
      is not maintained by frequency-dependent immune selection. By including 36
      isolates from Flores Island, Indonesia, and 19 isolates from Thaton, Myanmar, we
      investigated geographical patterns of sequence polymorphism for these epitopes in
      Southeast Asia; among the characterized isolates, a globally distributed variant
      appears to be predominant in Vietnam (75 of 142 isolates, or 52.8%) as well as in
      Myanmar (15 of 19 isolates, or 78.9%) and Indonesia (31 of 36 isolates, or
      86.1%). Further analyses involving worldwide CSP sequences revealed distinct
      regional patterns, a finding which, together with the unique mutations observed
      here, may suggest a possible role for host or local factors in the generation of
      sequence diversity in the T-cell epitopes of CSP.

PMID- 16597844
TI  - Performance of the gen-probe transcription-mediated [corrected] amplification
      research assay compared to that of a multitarget real-time PCR for Mycoplasma
      genitalium detection.
AB  - Mycoplasma genitalium (MG) can cause nongonococcal urethritis and is potentially
      associated with urethritis, endometritis, and cervicitis. Several assays have
      been developed to detect MG. Molecular amplification assays for organism
      detection can be problematic due to the potential for false-positive and false
      negative results. Confirmatory testing is often required in these situations,
      requiring additional time and resources. Use of multigene targets could integrate
      both detection and verification at lower cost. Utilizing two targets, the MgPa
      adhesion gene and the 16S rRNA gene, a multitarget real-time (MTRT) PCR for the
      detection of MG was developed. Samples from patients attending sexually
      transmitted disease clinics were collected in duplicate. Urine samples from males
      (n = 286) and self-collected vaginal swabs from females (n = 321) were analyzed
      by MTRT PCR for MG and the Gen-Probe transcription-mediated [corrected]
      amplification (TMA) assay, which targets MG rRNA for detection (TMA-MG research
      use only). Utilizing the criteria of any two targets being positively amplified,
      the MTRT PCR had a sensitivity and specificity of 91.8% (101 positive samples/110
      samples tested) and 99.5% (495/497), respectively, with a positive predictive
      value (PPV) of 98.1% (101/103) and a negative predictive value (NPV) of 98.2%
      (495/504). The Gen-Probe TMA-MG assay had a sensitivity, specificity, PPV, and
      NPV of 98.1% (108/110), 98.1% (488/497), 92.3% (108/117), and 99.5% (488/490),
      respectively. Comparison between the MTRT PCR and TMA-MG assay by kappa statistic
      analysis indicated that an overall kappa value was 0.941 (95% confidence
      interval, 0.907 and 0.976). Both assays demonstrated accuracy in the detection of
      MG from urine samples from male patients and self-collected vaginal swabs from
      female patients.

PMID- 16597845
TI  - Development of conventional and real-time nucleic acid sequence-based
      amplification assays for detection of Chlamydophila pneumoniae in respiratory
      specimens.
AB  - Isothermal nucleic acid sequence-based amplification (NASBA) was applied to the
      detection of Chlamydophila pneumoniae 16S rRNA by using the NucliSens basic kit
      (bioMerieux, Boxtel, The Netherlands). The assay was originally developed as a
      conventional NASBA assay with electrochemiluminescence detection and was
      subsequently adapted to a real-time NASBA format by using a molecular beacon. C.
      pneumoniae RNA prepared from a plasmid construct was used to assess the
      analytical sensitivity of the assay. The sensitivity of the NASBA assay was 10
      molecules of in vitro wild-type C. pneumoniae RNA and 0.1 inclusion-forming unit
      (IFU) of C. pneumoniae. In spiked respiratory specimens, the sensitivity of the
      C. pneumoniae NASBA assay varied between 0.1 and 1 IFU/100 mul sample, depending
      on the type of specimen. Finally, conventional and real-time NASBA were applied
      to respiratory specimens previously tested by PCR. A 100% concordance between the
      test results was obtained.

PMID- 16597846
TI  - Effects of delayed-entry conditions on the recovery and detection of
      microorganisms from BacT/ALERT and BACTEC blood culture bottles.
AB  - Manufacturers generally recommend that blood culture bottles be loaded into
      instruments within a short time of collection. However, in our experience, delays
      often occur prior to loading the bottles. We examined the effect of holding
      bottles under various temperatures (T)-room temperature (RT), 4 degrees C, 37
      degrees C, and RT for 2 h following incubation at 37 degrees C (to simulate
      transit [TR])-and for various holding times of 4, 12, and 24 h. We utilized the
      BacT/ALERT system with FA and FN bottles and the BACTEC system with Plus (PL) and
      Lytic 10 (LY) bottles. Standardized inocula and 5 ml of blood were added to each
      bottle. Fifteen organisms were evaluated based upon expected performance: aerobic
      (FA and PL), anaerobic (FN and LY 10), and facultative (all bottles). Based upon
      expected performance, the FA and FN bottles recovered 458 of 468 organisms and
      282 of 288 organisms, respectively, whereas the PL and LY bottles recovered 453
      of 468 organisms and 257 of 288 organisms, respectively (P = <0.001, FN versus
      LY). There were 3, 11, 21, and 27 false-negative results for bottles held at 4
      degrees C, RT, 37 degrees C, and TR, respectively. There were 4, 8, and 50 false
      negative results for bottles held for 4, 12, and 24 h, respectively. Our results
      support holding these four bottle types at 4 degrees C or at RT for up to 24 h
      and at 37 degrees C for up to 12 h. We propose that manufacturers only need to
      make claims for "delayed entry" when these bottles are held for more than 24 h at
      4 degrees C or at RT or for more than 12 h at 37 degrees C.

PMID- 16597847
TI  - Characteristic signatures of the lytA gene provide a basis for rapid and reliable
      diagnosis of Streptococcus pneumoniae infections.
AB  - The nucleotide sequences of the lytA gene from 29 pneumococcal isolates of
      various serotypes and 22 additional streptococci of the mitis group (including
      two Streptococcus pseudopneumoniae strains) have been compared and found to
      correspond to 19 typical (927-bp-long) and 20 atypical (921-bp-long) alleles. All
      the Streptococcus pneumoniae strains harbored typical lytA alleles, whereas
      nonpneumococcal isolates belonging to the mitis group always carried atypical
      alleles. A sequence alignment showed that the main difference between typical and
      atypical lytA alleles resided in 102 nucleotide positions (including the 6 bp
      absent from atypical alleles). These nucleotides were perfectly conserved in all
      the typical alleles studied, and the corresponding nucleotides of the atypical
      alleles were also perfectly conserved. The presence in these signatures of
      distinctive restriction sites (namely, SnaBI, XmnI, and BsaAI) allowed the
      development of a simple, reliable, and fast method that combines PCR
      amplification of the lytA gene, digestion with BsaAI, and separation of the
      products by agarose gel electrophoresis. This assay allows the rapid and
      consistent identification of true S. pneumoniae strains and represents an
      improved diagnostic tool for the study of pneumococcal carriage.

PMID- 16597848
TI  - Phylogenetic lineages of invasive and colonizing strains of serotype III group B
      Streptococci from neonates: a multicenter prospective study.
AB  - This study compares the phylogenetic lineages of invasive serotype III group B
      streptococci (GBS) to those of colonizing strains in order to determine lineages
      associated with invasive disease. Isolates from 29 infants with early-onset
      disease (EOD) and from 196 colonized infants, collected in a prospective,
      multicenter study, were assigned a sequence type (ST) by multilocus sequence
      typing. Overall, 54.5% of the isolates were in the ST-19 complex, and 40.4% were
      in the ST-17 complex. Invasive strains were more likely to be in the ST-17
      complex than were colonizing strains (59% versus 38%, P = 0.03). After we
      adjusted for potential confounders, the ST-17 complex was more likely to be
      associated with EOD than were other lineages (odds ratio = 2.51, 95% confidence
      interval = 1.02 to 6.20). These data support the hypothesis that ST-17 complex
      GBS are more virulent than other serotype III GBS.

PMID- 16597849
TI  - Molecular epidemiology of norovirus in outbreaks of gastroenteritis in southwest
      Germany from 2001 to 2004.
AB  - The identification and molecular epidemiology of norovirus in outbreaks of
      gastroenteritis were studied during a 3-year period in Germany. Specimens (n =
      316) from 159 nonbacterial gastroenteritis outbreaks from March 2001 to June 2004
      were analyzed for the presence of noroviruses by reverse transcriptase PCR.
      Outbreaks were most frequent in elderly people's homes and care centers (43%),
      followed by hospitals (24%). Molecular analyses of strains from 148 outbreaks
      showed that there were up to 12 genotypes involved in the outbreaks. Genogroup II
      noroviruses were responsible for 95% of the outbreaks. Cocirculation of more than
      one strain in the same outbreak and cocirculation of genogroup I and II strains
      in the same place were observed. Genogroup II4 (Grimsby-like) was the most
      prevalent strain, accounting for 48% and 67% of the outbreaks in 2002 and 2003,
      respectively. The genogroup IIb (Castell/Suria) genotype was observed in all the
      years of the study. Epidemiological and molecular data indicated that there was a
      major shift of the predominant strain that coincided with the appearance of a new
      variant of genogroup II4 in 2002. By the application of reverse transcriptase
      PCR, this study has demonstrated the importance and dynamism of noroviruses in
      Germany.

PMID- 16597850
TI  - Description of Mycobacterium conceptionense sp. nov., a Mycobacterium fortuitum
      group organism isolated from a posttraumatic osteitis inflammation.
AB  - A nonpigmented rapidly growing mycobacterium was isolated from wound liquid
      outflow, bone tissue biopsy, and excised skin tissue from a 31-year-old woman who
      suffered an accidental open right tibia fracture and prolonged stay in a river.
      The three isolates grew in 3 days at 24 to 37 degrees C. 16S rRNA sequence
      analyses over 1,483 bp showed that they were identical and shared 99.7% (4-bp
      difference) sequence similarity with that of Mycobacterium porcinum, the most
      closely related species. Partial rpoB (723 bp) sequence analyses showed that the
      isolates shared 97.0% sequence similarity with that of M. porcinum. Further
      polyphasic approaches, including biochemical tests, antimicrobial susceptibility
      analyses, and hsp65, sodA, and recA gene sequence analysis, as well as % G+C
      determination and cell wall fatty acid composition analysis supported the
      evidence that these isolates were representative of a new species. Phylogenetic
      analyses showed the close relationship with M. porcinum in the Mycobacterium
      fortuitum group. The isolates were susceptible to most antibiotics and exhibited
      evidence for penicillinase activity, in contrast to M. porcinum. We propose the
      name Mycobacterium conceptionense sp. nov. for this new species associated with
      posttraumatic osteitis. The type strain is D16(T) (equivalent to CIP 108544(T)
      and CCUG 50187(T)).

PMID- 16597851
TI  - Identification and quantification of archaea involved in primary endodontic
      infections.
AB  - Members of the domain Archaea, one of the three domains of life, are a highly
      diverse group of prokaryotes, distinct from bacteria and eukaryotes. Despite
      their abundance and ubiquity on earth, including their close association with
      humans, animals, and plants, so far no pathogenic archaea have been described. As
      some archaea live in close proximity to anaerobic bacteria, for instance, in the
      human gut system and in periodontal pockets, the aim of our study was to assess
      whether archaea might possibly be involved in human endodontic infections, which
      are commonly polymicrobial. We analyzed 20 necrotic uniradicular teeth with
      radiographic evidence of apical periodontitis and with no previous endodontic
      treatment. Using real-time quantitative PCR based on the functional gene mcrA
      (encoding the methyl coenzyme M reductase, specific to methanogenic archaea) and
      on archaeal 16S rRNA genes, we found five cases to be positive. Direct sequencing
      of PCR products from both genes showed that the archaeal community was dominated
      by a Methanobrevibacter oralis-like phylotype. The size of the archaeal
      population at the diseased sites ranged from 1.3 x 10(5) to 6.8 x 10(5) 16S rRNA
      gene target molecule numbers and accounted for up to 2.5% of the total
      prokaryotic community (i.e., bacteria plus archaea). Our findings show that
      archaea can be intimately connected with infectious diseases and thus support the
      hypothesis that members of the domain Archaea may have a role as human pathogens.

PMID- 16597852
TI  - Follow-up on diagnostic proficiency of laboratories equipped to perform
      orthopoxvirus detection and quantification by PCR: the second international
      external quality assurance study.
AB  - Two years after the first external quality assurance study on bioterrorism
      relevant viruses, we have conducted a follow-up study on orthopoxvirus detection
      by PCR. Thirty-three laboratories (27 European, 4 Austral-Asian, and 2 American)
      participated. Samples contained 0 to 40,000,000 DNA copies of lyophilized
      monkeypox, cowpox, and vaccinia virus per ml. Laboratories achieved a >80%
      detection chance above 56,234 copies per ml. Global sensitivity was not
      significantly improved over that of the first study. Twenty-seven and 9
      participants, respectively, were able to genotype and quantify virus. Four of 27
      genotyping results were incorrect. Quantification accuracy was significantly
      better for vaccinia virus than for the other viruses. False-positive results
      occurred in 22 (11.8%) of all 186 tests on negative samples, but 18 of these were
      contributed by only five laboratories. Fifty-five percent of laboratories could
      appropriately detect PCR inhibition. The use of either real-time PCR or
      commercial diagnostic kits had significant positive influence on laboratory
      performance.

PMID- 16597853
TI  - Molecular epidemiology and evolution in an outbreak of fulminant hepatitis B
      virus.
AB  - In order to establish the transmission pathway for two outbreak patients affected
      by fulminant hepatitis B (FHB) following a shared period of hospitalization, we
      sequenced the complete genomes of the hepatitis B viruses (HBV) isolated from
      them as well as from the suspected common source and 11 additional controls.
      Phylogenetic and statistical analyses of these sequences revealed that the two
      FHB patients were indeed infected by a common source and that the fatal
      development of the disease did not appear to be associated with any mutation
      previously reported to be related to FHB. These data have also allowed us to
      estimate the extent and distribution of genetic variability along the genomes of
      HBV genotype D samples from the same source population. As a result of these
      analyses, we provide an improved statistical method to individualize the
      assignment of each suspected patient and the source of an outbreak and
      information on which genome region to analyze in the molecular epidemiological
      assessment of hepatitis B virus transmission cases.

PMID- 16597854
TI  - Development of real-time reverse transcriptase PCR assays to detect and serotype
      dengue viruses.
AB  - Serotyping dengue virus (DENV) from suspect human specimens is crucial for
      developing sound epidemiological control measurements early in the transmission
      season and for effective patient management. We modified DENV consensus D1 (mD1)
      and serotype-specific TS2 (mTS2) and redesigned serotype-specific TS1 (rTS1) and
      TS4 (rTS4) as described previously in the conventional capsid and premembrane
      gene (C-prM) protocol (R. S. Lanciotti, C. H. Calisher, D. J. Gubler, G.-J.
      Chang, A. V. Vorndam, J. Clin. Microbiol. 30:545-551, 1992). In addition, we
      designed two new sets of amplimers and probes, located at nonstructural protein 5
      (NS5) and the 3' noncoding region (3'NC) of DENV. The NS5 protocol utilizes two
      flaviviral consensus outer amplimers (mFU1 and CFD2) and four dengue virus
      serotype-specific TaqMan fluorogenic probes. The 3'NC protocol uses two DENV
      consensus amplimers, DC10418 and CDC10564. The conventional gel-based, heminested
      detection method was adapted for the C-prM protocol for detecting and serotyping
      dengue viruses. In addition, we developed the real-time SYBR green I and
      postamplification melting temperature curve analysis for the mD1/TS and 3'NC
      protocols using identical amplification conditions. The NS5 amplimer/probe set
      was formulated as a one-tube, multiplex, real-time reverse transcriptase PCR for
      serotype identification. Three sets of amplimers and probes were verified for
      their specificity in tests with yellow fever, Japanese encephalitis, St. Louis
      encephalitis, and West Nile viruses; optimized against 109 DENV strains; and
      validated for detection of the virus in sera from two different panels of acute
      phase human dengue serum specimens and one panel of virus isolates from dengue
      patients' serum specimens. Clinical evaluation by two separate laboratories
      indicated that the C-prM was more sensitive (100%) than the NS5 (91%) or the 3'NC
      (91%) protocol.

PMID- 16597855
TI  - New commercially available PCR and microplate hybridization assay for detection
      and differentiation of human polyomaviruses JC and BK in cerebrospinal fluid,
      serum, and urine samples.
AB  - JC and BK human polyomaviruses (family Polyomaviridae) may cause severe
      neurological or urinary tract pathologies in immunocompromised hosts. In the
      present study, we evaluated a new commercially available PCR and microplate
      colorimetric hybridization assay for the standardized differential detection of
      JC virus (JCV) and BK virus (BKV) genomes in clinical samples. This JC/BK
      Consensus test was first evaluated by testing serial dilutions of JCV or BKV
      plasmid DNA standards and was then compared with an in-house reference PCR assay
      for the detection of JC and BK virus genomes in 70 cerebrospinal fluid (CSF)
      samples of patients with neurological disorders and in 75 serum or plasma samples
      and 125 urine samples of renal graft recipients. This new test allowed a limit of
      detection of 10 copies and 1 copy of JC and BK virus genomes, respectively, and
      was able to differentiate various levels of JCV, BKV, and mixed JCV and BKV DNA
      genomes in a single reaction tube. Our results showed 100% specificity and
      sensitivity for the JC/BK Consensus test with CSF samples. With serum or plasma
      samples, this test had a sensitivity and a specificity of 100% for both JCV and
      mixed JCV and BKV DNA detection and a sensitivity and a specificity of 100 and
      97.8% for BKV DNA detection, respectively. With urine samples, the sensitivity
      and specificity were 100 and 96.6%, respectively, for JCV DNA detection; 100 and
      89.4%, respectively, for BKV DNA detection; and 44.4 and 100%, respectively, for
      mixed JCV and BKV DNA detection. In conclusion, our data indicate that this new
      test, the JC/BK Consensus test, is valuable for the sensitive and specific
      differential detection of single JCV and BKV infections in CSF, serum or plasma,
      and urine samples. The use of this reliable PCR assay would improve the routine
      virological diagnosis as well as the clinical care of immunocompromised patients
      with polyomavirus-related pathologies.

PMID- 16597856
TI  - Presence of E6 and E7 mRNA from human papillomavirus types 16, 18, 31, 33, and 45
      in the majority of cervical carcinomas.
AB  - The oncogenic potential of the human papillomavirus (HPV) early genes E6 and E7
      is well established and a source of interest with regard to HPV testing for
      cervical carcinoma. Here we present a study performed with 204 histologically
      confirmed invasive cervical squamous cell carcinomas (SCCs) in which we evaluated
      the HPV E6 and E7 mRNA detection assay PreTect HPV-Proofer for detection of high
      risk HPV types 16, 18, 31, 33, and 45. For further evaluation, detection of E6
      and E7 mRNA from HPV types 35, 52, and 58 by real-time multiplex nucleic acid
      sequence-based amplification was also included. For comparison and to assess the
      overall prevalence of various HPV types, samples were also tested for HPV DNA by
      both consensus and type-specific PCR, reverse line blotting, sequencing, and in
      situ hybridization. The overall prevalence of HPV was 97%. HPV E6 and E7
      transcripts were detected in 188 of 204 (92%) biopsy specimens, of which 181
      contained one of the following HPV types: 16, 18, 31, 33, or 45. Consensus PCR
      and type-specific PCR detected HPV in 187 of 204 and 188 of 204 (92%) specimens,
      respectively. In conclusion, this study verifies the presence of HPV E6 and E7
      mRNA in SCCs and demonstrates that HPV infections among Norwegian women with SCCs
      are limited mainly to the five high-risk types, 16, 18, 31, 33, and 45. This,
      together with the fact that PreTect HPV-Proofer detects the HPV oncogenic
      transcripts, suggests that the assay is a valuable approach in the field of HPV
      detection in cervical carcinoma.

PMID- 16597857
TI  - Incidence and time course of Leishmania infantum infections examined by
      parasitological, serologic, and nested-PCR techniques in a cohort of naive dogs
      exposed to three consecutive transmission seasons.
AB  - Most experience in the comparison of diagnostic tools for canine leishmaniasis
      comes from cross-sectional surveys of dogs of different ages and breeds and in
      cases with unknown onset and duration of leishmaniasis. A longitudinal study was
      performed on 43 beagle dogs exposed to three transmission seasons (2002 to 2004)
      of Mediterranean leishmaniasis and examined periodically over 32 months through
      bone marrow microscopy and nested PCR (n-PCR), lymph node culture, serology
      (immunofluorescent-antibody test), and evaluation of clinical parameters.
      Starting from January 2003, the highest rate of positives was detected by n-PCR
      at all assessments (from 23.3% to 97.3%). Sensitivities of serologic and
      parasitological techniques were lower but increased with time, from 15.8% to 75.0
      to 77.8%. Some dogs that tested positive by n-PCR but negative by other tests
      ("subpatent infection") remained so until the end of the study or converted to
      negative in subsequent assessments, whereas all dogs with positive serology
      and/or microscopy/culture ("asymptomatic patent infection") exhibited progressive
      leishmaniasis; 68% of them developed clinical disease ("symptomatic patent
      infection") during the study, at 7 (range, 3 to 14) months after being positive
      to all tests. Postexposure infection incidences were high and were significantly
      different between 2002 and 2003 exposures (39.5% and 91.7%, respectively). The
      time course of infection was highly variable in each dog, with three patterns
      being identified: (i) rapid establishment of a patent condition (0 to 2 months
      from detection of infection); (ii) a prolonged subpatent condition (4 to 22
      months) before progression; and (iii) a transient subpatent condition followed by
      10 to 21 months of apparent Leishmania-negative status before progression.

PMID- 16597858
TI  - Use of a variable amplicon typing scheme reveals considerable variation in the
      accessory genomes of isolates of Burkholderia pseudomallei.
AB  - Melioidosis, a disease caused by the bacterium Burkholderia pseudomallei, is
      endemic in southeast Asia and northern Australia. We used suppression subtractive
      hybridization (SSH) to identify sequences that varied between two B. pseudomallei
      isolates from Australia and determined the distribution of 45 SSH-derived
      sequences among a panel of B. pseudomallei and B. thailandensis isolates.
      Sequences exhibiting variable prevalence were included in a variable amplicon
      typing (VAT) scheme designed to score the presence or absence of 14 PCR
      amplicons. VAT analysis was carried out with 48 isolates from Thailand, which
      were typed by multilocus sequence typing (MLST), and 44 isolates from Australia
      of known MLST type. The VAT scheme could be used to divide the 48 isolates from
      Thailand into 23 VAT types and the 44 isolates from Australia into 36 VAT types.
      Some of the sequences included in the VAT scheme were more commonly PCR positive
      among isolates from Australia than among isolates from Thailand, and vice versa.
      No isolate from Australia was PCR positive for genomic island 11 or a putative
      transposase sequence, whereas four SSH-derived sequences were far more prevalent
      among the Australian isolates. Analysis based on the VAT scheme indicated that
      the isolates clustered into groups, some of which were mainly or exclusively from
      one geographical origin. One cluster included Australian isolates that were
      mostly associated with severe disease, including rare neurological melioidosis,
      suggesting that the content of the accessory genome may play an important role in
      determining the clinical manifestation of the disease.

PMID- 16597859
TI  - Is serological testing a reliable tool in laboratory diagnosis of syphilis? Meta
      analysis of eight external quality control surveys performed by the german
      infection serology proficiency testing program.
AB  - The accuracy of diagnostic tests is critical for successful control of epidemic
      outbreaks of syphilis. The reliability of syphilis serology in the nonspecialist
      laboratory has always been questioned, but actual data dealing with this issue
      are sparse. Here, the results of eight proficiency testing sentinel surveys for
      diagnostic laboratories in Germany between 2000 and 2003 were analyzed. Screening
      tests such as Treponema pallidum hemagglutination assay (mean accuracy, 91.4%
      [qualitative], 75.4% [quantitative]), Treponema pallidum particle agglutination
      assay (mean accuracy, 98.1% [qualitative], 82.9% [quantitative]), and enzyme
      linked immunosorbent assays (ELISAs) (mean qualitative accuracy, 95%) were more
      reliable than Venereal Disease Research Laboratory (VDRL) testing (mean accuracy,
      89.6% [qualitative], 71.1% [quantitative]), the fluorescent treponemal antibody
      absorption test (FTA-ABS) (mean accuracy, 88% [qualitative], 65.8%
      [quantitative]), and immunoblot assays (mean qualitative accuracy, 87.3%).
      Clearly, immunoglobulin M (IgM) tests were more difficult to manage than IgG
      tests. False-negative results for samples that have been unambiguously determined
      to be IgM and anti-lipoid antibody positive accounted for 4.7% of results in the
      IgM ELISA, 6.9% in the VDRL test, 18.5% in the IgM FTA-ABS, and 23.0% in the IgM
      immunoblot assay. For negative samples, the mean percentage of false-positive
      results was 4.1% in the VDRL test, 5.4% in the IgM ELISA, 0.7% in the IgM FTA
      ABS, and 1.4% in the IgM immunoblot assay. On average, 18.3% of participants
      misclassified samples from patients with active syphilis as past infection
      without indicating the need for further treatment. Moreover, 10.2% of
      laboratories wrongly reported serological evidence for active infection in
      samples from patients with past syphilis or in sera from seronegative blood
      donors. Consequently, the continuous participation of laboratories in proficiency
      testing and further standardization of tests is strongly recommended to achieve
      better quality of syphilis serology.

PMID- 16597860
TI  - Time to blood culture positivity as a predictor of clinical outcome of
      Staphylococcus aureus bloodstream infection.
AB  - Few studies have assessed the time to blood culture positivity as a predictor of
      clinical outcome in bloodstream infections (BSIs). The purpose of this study was
      to evaluate the time to positivity (TTP) of blood cultures in patients with
      Staphylococcus aureus BSIs and to assess its impact on clinical outcome. We
      performed a historical cohort study with 91 adult patients with S. aureus BSIs.
      TTP was defined as the time between the start of incubation and the time that the
      automated alert signal indicating growth in the culture bottle sounded. Patients
      with BSIs and TTPs of culture of </=12 h (n = 44) and >12 h (n = 47) were
      compared. Septic shock occurred in 13.6% of patients with TTPs of </=12 h and in
      8.5% of patients with TTP of >12 h (P = 0.51). A central venous catheter source
      was more common with a BSI TTP of </=12 h (P = 0.010). Univariate analysis
      revealed that a Charlson score of >/=3, the failure of at least one organ
      (respiratory, cardiovascular, renal, hematologic, or hepatic), infection with
      methicillin-resistant S. aureus, and TTPs of </=12 h were associated with death.
      Age, gender, an APACHE II score of >/=20 at BSI onset, inadequate empirical
      antibiotic therapy, hospital-acquired bacteremia, and endocarditis were not
      associated with mortality. Multivariate analysis revealed that independent
      predictors of hospital mortality were a Charlson score of >/=3 (odds ratio [OR],
      14.4; 95% confidence interval [CI], 2.24 to 92.55), infection with methicillin
      resistant S. aureus (OR, 9.3; 95% CI, 1.45 to 59.23), and TTPs of </=12 h (OR,
      6.9; 95% CI, 1.07 to 44.66). In this historical cohort study of BSIs due to S.
      aureus, a TTP of </=12 h was a predictor of the clinical outcome.

PMID- 16597861
TI  - Origin of class 1 and 2 integrons and gene cassettes in a population-based sample
      of uropathogenic Escherichia coli.
AB  - The prevalence of urinary tract infections (UTI) caused by trimethoprim
      sulfamethoxazole (TMP-SMX)-resistant Escherichia coli is increasing and varies
      geographically in the United States. Recent community-based UTI studies have
      demonstrated geographic clustering of an Escherichia coli clonal group,
      suggesting occurrence of a community outbreak of UTI. A large proportion of this
      clonal group (designated CgA) isolated from women in a California college
      community was found to be resistant to TMP-SMX. We wished to determine if the
      acquisition of TMP-SMX resistance by CgA occurred before or after the CgA strains
      were introduced into this community. Between October 1999 and January 2000 and
      between October 2000 and January 2001, 482 E. coli isolates were consecutively
      collected from the urine samples of women with UTI at a student health clinic and
      analyzed for determinants of TMP-SMX resistance. In particular, the distribution
      of integrons harboring resistance cassettes for TMP-SMX (dfr) was examined. Among
      95 TMP-SMX-resistant isolates, 68 and 27 isolates carried class 1 and class 2
      integrons, respectively. A class 1 integron was found in 25 (93%) of 27 TMP-SMX
      resistant CgA isolates but in only 43 (63%) of 68 TMP-SMX-resistant non-CgA
      isolates (P < 0.001) and in none of 44 TMP-SMX-susceptible E. coli isolates (P <
      0.0001). CgA strains carried only a single arrangement of class 1 gene cassettes
      (dfrA17-aadA5), while the non-clonal group strains carried nine different
      cassette arrangements. These results support the idea that CgA strains acquired
      their resistance at a common site prior to their spread to the college community.

PMID- 16597862
TI  - Occurrence of overlooked zoonotic tuberculosis: detection of Mycobacterium bovis
      in human cerebrospinal fluid.
AB  - The paucibacillary nature of the cerebrospinal fluid (CSF) has been a major
      obstacle in the diagnosis of human tuberculous meningitis (TBM). This study shows
      that with molecular techniques direct precise determination to the species level
      of mycobacterial pathogens can be made. The present report describes the utility
      of a nested PCR (N-PCR) assay (A. Mishra, A. Singhal, D. S. Chauhan, V. M.
      Katoch, K. Srivastava, S. S. Thakral, S. S. Bharadwaj, V. Sreenivas, and H. K.
      Prasad, J. Clin. Microbiol. 43:5670-5678, 2005) in detecting M. tuberculosis and
      M. bovis in human CSF. In 2.8% (6/212) of the samples, M. tuberculosis was
      detected, and in 17% (36/212), M. bovis was detected. Mixed infection was
      observed in 22 samples. Comparative analysis of clinical diagnosis, smear
      microscopy, and N-PCR in 69 patients (TBM, 25; non-TBM, 44) showed that the
      sensitivity of N-PCR (61.5%) was greater than that of smear microscopy (38.4%).
      Determination to the species level is important from the viewpoint of determining
      the prevalence of these mycobacteria in a community and would influence
      strategies currently adopted for the prevention of tuberculosis.

PMID- 16597863
TI  - 16S rRNA gene sequencing versus the API 20 NE system and the VITEK 2 ID-GNB card
      for identification of nonfermenting Gram-negative bacteria in the clinical
      laboratory.
AB  - Over a period of 26 months, we have evaluated in a prospective fashion the use of
      16S rRNA gene sequencing as a means of identifying clinically relevant isolates
      of nonfermenting gram-negative bacilli (non-Pseudomonas aeruginosa) in the
      microbiology laboratory. The study was designed to compare phenotypic with
      molecular identification. Results of molecular analyses were compared with two
      commercially available identification systems (API 20 NE, VITEK 2 fluorescent
      card; bioMerieux, Marcy l'Etoile, France). By 16S rRNA gene sequence analyses,
      92% of the isolates were assigned to species level and 8% to genus level. Using
      API 20 NE, 54% of the isolates were assigned to species and 7% to genus level,
      and 39% of the isolates could not be discriminated at any taxonomic level. The
      respective numbers for VITEK 2 were 53%, 1%, and 46%, respectively. Fifteen
      percent and 43% of the isolates corresponded to species not included in the API
      20 NE and VITEK 2 databases, respectively. We conclude that 16S rRNA gene
      sequencing is an effective means for the identification of clinically relevant
      nonfermenting gram-negative bacilli. Based on our experience, we propose an
      algorithm for proper identification of nonfermenting gram-negative bacilli in the
      diagnostic laboratory.

PMID- 16597864
TI  - Reactivity of genotype-specific recombinant proteins of human erythrovirus B19
      with plasmas from areas where genotype 1 or 3 is endemic.
AB  - Human erythrovirus (parvovirus) B19 (B19) is a common human pathogen. The recent
      discovery of three genotypes, 1 to 3, raised issues related to the ability of
      genotype-specific antigens to cross-react with antibodies elicited by other
      genotypes. This study assessed antibody capture and immunoglobulin G (IgG) cross
      reactivity between genotype 1 and genotype 3 recombinant antigens and analyzed
      the potential gain of adding VP1 protein to VP2 capsid antigen. Plasma samples
      from genotype 1- or genotype 3-infected populations were blindly tested with
      blindly prepared reagents. The IgG reactivity was assessed with baculovirus
      expressed VP2 or VP1 and VP2 recombinant genotype 1 or genotype 3 proteins in a
      standardized enzyme immunoassay (EIA). A high degree of agreement (>95%) between
      EIA results was observed, with Spearman correlation coefficient and kappa
      reliability coefficient results of >/=0.95 for samples from the United Kingdom
      and >/=0.77 for samples from Ghanaian children, respectively. Most discrepant
      results were related to equivocal reactivity. The addition of VP1 to VP2 capsids
      did not significantly impact antibody detection. These data suggest that the
      currently available genotype-1-based IgG EIA is suitable to detect antibody to
      B19 genotype 3 in Ghanaian children. However, samples from the Ghanaian adult
      population exhibited atypical results in the assay, possibly due to the high
      levels of nonspecific IgG antibodies found in adults living in this region.
      Within these limitations, the study demonstrates that genotype 1 and genotype 3
      antigens are equally effective in detecting either antibody species.

PMID- 16597865
TI  - Rapid detection of norovirus from fecal specimens by real-time reverse
      transcription-loop-mediated isothermal amplification assay.
AB  - In this study, we developed a one-step, single-tube genogroup-specific reverse
      transcription-loop-mediated isothermal amplification (RT-LAMP) assay for the
      detection of norovirus (NoV) genomes targeting from the C terminus of the RNA
      dependent RNA polymerase gene to the capsid N-terminal/shell domain region. This
      is the first report on the development of an RT-LAMP assay for the detection of
      NoV genomes. Because of the diversity of NoV genotypes, we used 9 and 13
      specially designed primers containing mixed bases for genogroup I (GI) and II
      (GII), respectively. The RT-LAMP assay had the advantages of rapidity,
      simplicity, specificity, and selectively and could obtain results within 90 min,
      generally even within 60 min, under isothermal conditions at 62 degrees C. The
      detection limits for NoV genomes were between 10(2) and 10(3) copies/tube for GI
      and GII with differentiation by genotype, and no cross-reactions among NoV GI and
      GII and other gastroenteritis viruses, such as sapovirus, human astrovirus,
      adenovirus type 40 and 41, and group A and C rotavirus, were found. In the
      evaluation tests with fecal specimens obtained from gastroenteritis outbreaks,
      the sensitivity and specificity of the RT-LAMP assay with regard to RT-PCR were
      100 and 94% for GI and 100 and 100% for GII, respectively. These findings
      establish that the RT-LAMP assay is potentially useful for the rapid detection of
      NoV genomes from fecal specimens in outbreaks of food-borne and person-to-person
      transmitted gastroenteritis.

PMID- 16597866
TI  - Genotyping of Toxoplasma gondii by multiplex PCR and peptide-based serological
      testing of samples from infants in Poland diagnosed with congenital
      toxoplasmosis.
AB  - Toxoplasma gondii has a clonal population genetic structure with three (I, II,
      and III) lineages that predominate in North America and Europe. Type II strains
      cause most cases of symptomatic human infections in France and the United States,
      although few other regions have been adequately sampled. Here we determined the
      parasite genotype in amniotic fluid and cerebrospinal fluid samples from
      congenital toxoplasmosis cases in Poland. Nineteen confirmed congenital cases of
      toxoplasmosis were analyzed, including both severe and asymptomatic cases. The
      genotype of parasite strains causing congenital infection was determined by
      direct PCR amplification and restriction fragment length polymorphism analysis.
      Nested multiplex PCR analysis was used to type four independent polymorphic
      markers. The sensitivity of multiplex nested PCR was >/=25 parasites/ml in
      amniotic fluid and cerebral spinal fluid samples. Parasite DNA was successfully
      amplified in 9 of 19 samples (eight severely affected and one asymptomatic
      fetus). Only genotype II parasites were identified as the source of T. gondii
      infection based on restriction fragment length polymorphism analysis. Strains
      causing congenital infections were also typed indirectly based on detection of
      antibodies to strain-specific peptides. Serotyping indicated that 12 of 15 cases
      tested were caused by type II strains and these positives included both
      symptomatic and asymptomatic infections. Overall, the combined analysis indicated
      that 14 of the cases were caused by type II strains. Our results are consistent
      with the hypothesis that parasite burden is associated with severity of
      congenital toxoplasmosis and indicate that serological testing provides a
      promising method for genotypic analysis of toxoplasmosis.

PMID- 16597867
TI  - Evaluation of the COBAS AmpliPrep-total nucleic acid isolation-COBAS TaqMan
      hepatitis B virus (HBV) quantitative test and comparison to the VERSANT HBV DNA
      3.0 assay.
AB  - Quantitative detection of hepatitis B virus (HBV) in serum or plasma has become
      the most direct and reliable method for monitoring chronic hepatitis B. Here, we
      report the performance characteristics of a real-time PCR hepatitis B DNA
      quantitative assay, the COBAS TaqMan (CTM) HBV test (Roche Diagnostics, Meylan,
      France), in combination with an automated DNA extraction on the COBAS AmpliPrep
      (CAP) instrument using the total nucleic acid isolation kit (TNAI kit), a generic
      reagent for nucleic acid isolation (both from Roche Diagnostics). The linearity,
      accuracy, and specificity of the CAP-TNAI-CTM HBV test were evaluated using
      various reference panels and standards (HBV panel 2004 from Quality Control for
      Molecular Diagnostics, OptiQuant HBV panel from AcroMetrix, WHO International
      Standard for HBV, and Teragenix hepatitis B genotype panel). Quantitative results
      show that the CAP-TNAI-CTM HBV test performed well with respect to linearity,
      accuracy, and reproducibility from at least 100 to 500,000 HBV DNA IU/ml. Based
      on the log(10) IU of HBV DNA/ml measured, the intra-assay variation ranged from
      2.49% to 8.46% and the interassay variation ranged from 1.88% to 7.83%. The test
      was extremely sensitive and could detect samples containing HBV DNA below the
      reported quantification threshold (<30 IU/ml). All HBV genotypes were correctly
      amplified, and no cross-contamination occurred during the automated sample
      preparation. In addition, 402 human serum samples were tested comparatively to
      the VERSANT HBV DNA 3.0 assay (bDNA; Bayer Diagnostics, Puteaux, France). The
      viral load results of the CAP-TNAI-CTM test and bDNA were significantly
      correlated, but the agreement between the two tests was poor, with large
      differences between results for individual samples. The hands-on time was
      estimated to be reduced from 2.30 h with bDNA to 45 min with the CAP-TNAI-CTM
      test, and up to 84 samples were completely processed within a working day.
      Overall, the performance characteristics of the CAP-TNAI-CTM test demonstrated
      that it provides a high-throughput sensitive and reliable method for quantitation
      of HBV DNA levels in the routine molecular laboratory.

PMID- 16597868
TI  - Dynamics of appearance and expansion of a prolyliminopeptidase- negative subtype
      among Neisseria gonorrhoeae isolates collected in Sydney, Australia, from 2002 to
      2005.
AB  - Recent studies have demonstrated a wide geographic circulation of isolates of
      Neisseria gonorrhoeae that fail to produce prolyliminopeptidase (PIP). Tests
      based on the production of this enzyme are important elements of a number of
      identification systems for gonococci. We documented the appearance, expansion,
      and contraction of subtypes of 165 PIP-negative gonococci detected in an extended
      and systematic sample of the 3,926 N. gonorrhoeae isolates collected in Sydney,
      Australia, from July 2002 to September 2005. Their appearance, peak, and decline
      followed an "epidemic" curve. At the peak of their prevalence in 2003, PIP
      negative gonococci comprised 22% of all isolates. Closely related phenotypes
      accounted for 162/165 of the PIP-negative gonococci. Algorithms for confirmation
      of N. gonorrhoeae should take account of the temporal and geographic variability
      of gonococci by utilizing two or more distinct confirmatory methods.

PMID- 16597869
TI  - Use of TaqMan real-time reverse transcription-PCR for rapid detection,
      quantification, and typing of norovirus.
AB  - Noroviruses (NoVs) are the most commonly identified cause of outbreaks and
      sporadic cases of acute gastroenteritis. We evaluated and optimized NoV-specific
      TaqMan real-time reverse transcription (RT)-PCR assays for the rapid detection
      and typing of NoV strains belonging to genogroups GI and GII and adapted them to
      the LightCycler platform. We expanded the detection ability of the assays by
      developing an assay that detects the GIV NoV strain. The assays were validated
      with 92 clinical samples and 33 water samples from confirmed NoV outbreaks and
      suspected NoV contamination cases. The assays detected NoV RNA in all of the
      clinical specimens previously confirmed positive by conventional RT-PCR and
      sequencing. Additionally, the TaqMan assays successfully detected NoV RNA in
      water samples containing low viral concentrations and inhibitors of RT and/or
      PCR, whereas the conventional method with region B primers required dilution of
      the inhibitors. By means of serially diluted NoV T7 RNA transcripts, a potential
      detection limit of <10 transcript copies per reaction mixture was observed with
      the GII assay and a potential detection limit of <100 transcript copies per
      reaction mixture was observed with the GI assay. These results and the ability to
      detect virus in water that was negative by RT-PCR demonstrate the higher
      sensitivity of the TaqMan assay compared with that of a conventional RT-PCR
      assay. The TaqMan methods dramatically decrease the turnaround time by
      eliminating post-PCR processing. These assays have proven useful in assisting
      scientists in public health and diagnostic laboratories report findings quickly
      to outbreak management teams.

PMID- 16597870
TI  - Use of PCR and reverse line blot hybridization assay for rapid simultaneous
      detection and serovar identification of Chlamydia trachomatis.
AB  - The aim of this study was to develop and evaluate multiplex and nested PCR
      reverse line blot (RLB) hybridization assays for detection and serovar
      identification of Chlamydia trachomatis. Two sets of primers targeting the VD2
      region of the omp1 gene and one set targeting the cryptic plasmid were designed
      for use in multiplex (both targets) and nested PCR (omp1 only). For the RLB
      assay, labeled omp1 amplicons were hybridized to a membrane containing probes
      specific for 15 C. trachomatis serovars. The assays were used to test 429
      clinical specimens, which had been previously tested for C. trachomatis using the
      COBAS AMPLICOR system. Specimens were tested without knowledge of the COBAS
      AMPLICOR result. Of 205 specimens that were positive by COBAS AMPLICOR, 201 (98%)
      were positive by multiplex PCR-RLB and 188 (92%) were also positive by omp1
      nested PCR-RLB. In addition, three of 224 COBAS AMPLICOR-negative specimens were
      positive by omp1 nested PCR-RLB. One hundred sixty-six of 191 (87%) specimens in
      which C. trachomatis serovars were identified contained only one serovar and 25
      (13%) contained two or three serovars. Serovars D, E, and F were found in 31
      (16%), 83 (43%), and 51 (27%) specimens, respectively. Serovar E (41%) was the
      most commonly identified single serovar. Serovars J and K were found alone
      uncommonly (<2% each), but 18 of 25 (72%) specimens with multiple C. trachomatis
      serovars contained one or both (10 specimens) of these serovars. The nested
      (ompI) PCR-RLB is a specific and sensitive method for simultaneous detection and
      serovar identification of C. trachomatis, which can reliably identify mixed C.
      trachomatis serovars. It is suitable for use in epidemiological studies.

PMID- 16597871
TI  - Forty-eight-hour diagnosis of onychomycosis with subtyping of Trichophyton rubrum
      strains.
AB  - A novel strategy for the molecular identification of fungal agents of
      onychomycosis (including Trichophyton rubrum) has been designed based on the use
      of species-specific and universal primers in conjunction with a commercial kit
      that allows the extraction of DNA directly from the nail specimens. The
      microsatellite marker T1, which is based on a (GT)n repeat, was applied for the
      species-specific identification of Trichophyton rubrum. To evaluate how often
      Scopulariopsis spp. are detected in nail specimens, a second primer pair was
      designed to amplify specifically a 336-bp DNA fragment of the 28S region of the
      nuclear rRNA gene of S. brevicaulis and closely related species. Other fungal
      species were identified using amplification of the internal transcribed spacer
      (ITS) region of the rRNA gene, followed by restriction fragment length
      polymorphism analysis or sequencing. In addition, polyacrylamide gel separation
      of the T1-PCR product allowed subtyping of T. rubrum strains. We studied 195 nail
      specimens (the "nail sample") and 66 previously collected etiologic strains (the
      "strain sample") from 261 onychomycosis patients from Bulgaria and Greece. Of the
      etiologic agents obtained from both samples, T. rubrum was the most common
      organism, confirmed to be present in 76% of all cases and serving as the sole or
      (rarely) mixed etiologic agent in 199 of 218 cases (91%) where the identity of
      the causal organism(s) was confirmed. Other agents seen included molds (6% of
      cases with identified etiologic agents; mainly S. brevicaulis) and other
      dermatophyte species (4%; most frequently Trichophyton interdigitale).
      Simultaneous infections with two fungal species were confirmed in a small
      percentage of cases (below 1%). The proportion of morphologically identified
      cultures revealed by molecular study to have been misidentified was 6%. Subtyping
      revealed that all but five T. rubrum isolates were of the common type B that is
      prevalent in Europe. In comparison to microscopy and culture, the molecular
      approach was superior. The PCR was more sensitive (84%) than culture (22%) in the
      nail sample and was more frequently correct in specifically identifying etiologic
      agents (100%) than microscopy plus routine culture in either the nail or the
      strain samples (correct culture identifications in 96% and 94% of cases,
      respectively). Using the molecular approach, the time for diagnosing the identity
      of fungi causing onychomycosis could be reduced to 48 h, whereas culture
      techniques generally require 2 to 4 weeks. The early detection and identification
      of the infecting species in nails will facilitate prompt and appropriate
      treatment and may be an aid for the development of new antifungal agents.

PMID- 16597872
TI  - Oncogenic human papillomavirus (HPV) type distribution and HPV type 16 E6
      variants in two Spanish population groups with different levels of HPV infection
      risk.
AB  - The aim of this study is to determine oncogenic human papillomavirus (HPV) types
      and HPV type 16 (HPV16) variant distribution in two Spanish population groups,
      commercial sex workers and imprisoned women (CSW/IPW) and the general population.
      A multicenter cross-sectional study of 1,889 women from five clinical settings in
      two Spanish cities was conducted from May to November 2004. Oncogenic HPV
      infection was tested by an Hybrid Capture II (HC2) test, and positive samples
      were genotyped by direct sequencing using three different primer sets in L1
      (MY09/11 and GP5+/GP6+) and E6/E7. HPV16 variants were identified by sequencing
      the E6, E2, and L1 regions. Four hundred twenty-five samples were positive for
      the HC2 test, 31.5% from CSW/IPW and 10.7% from the general population. HPV16 was
      the most frequent type. Distinct profiles of oncogenic HPV type prevalence were
      observed across the two populations. In order of decreasing frequency, HPV types
      16, 31, 58, 66, 56, and 18 were most frequent in CSW/IPW women, and types 16, 31,
      52, 68, 51, and 53 were most frequent in the general population. We analyzed
      HPV16 intratype variants, and a large majority (78.7%) belonged to the European
      lineage. AA variants were detected in 16.0% of cases. African variants belonging
      to classes Af1 (4.0%) and Af2 (1.3%) were detected. Different HPV types and HPV16
      intratype variants are involved in oncogenic HPV infections in our population.
      These results suggest that HPV type distribution differs in CSW/IPW women and in
      the general population, although further analysis is necessary.

PMID- 16597873
TI  - Comparison of PCR assays for diagnosis of cutaneous leishmaniasis.
AB  - Three PCR assays for diagnosing leishmaniasis were compared and validated against
      parasite cultures and microscopic evaluation of stained tissue smears using 92
      specimens from suspected cases of cutaneous leishmaniasis (CL) in Israel and the
      West Bank. Samples from imported and locally acquired disease were examined. The
      kinetoplast DNA (kDNA) PCR showed the highest sensitivity (98.7%) of any assay,
      correctly diagnosing 77/78 of the confirmed positive samples, followed by the
      rRNA gene internal transcribed spacer 1 (ITS1) PCR (71/78 positive, 91.0%
      sensitivity) and then the spliced leader mini-exon PCR (42/78 positive, 53.8%
      sensitivity). Either parasite culture or microscopy alone detected 62.8% (49/78)
      or 74.4% (58/78) of the positive specimens, respectively, while culture and
      microscopy together improved overall sensitivity to 83.3% (65/78). Except for the
      kDNA PCR that had six false positives, all other assays were 100% specific.
      Further, restriction enzyme analysis of the ITS1 PCR product enabled
      identification of 74.6% of the positive samples, which included strains of
      Leishmania major (50.9%), Leishmania tropica (47.2%), and the Leishmania
      braziliensis complex (1.9%). This suggests that a PCR using kDNA should be used
      for the diagnosis of CL and that an ITS1 PCR can be reliably used for the
      diagnosis of CL when rapid species identification is needed.

PMID- 16597874
TI  - Simultaneous detection of pathogens in clinical samples from patients with
      community-acquired pneumonia by real-time PCR with pathogen-specific molecular
      beacon probes.
AB  - In this study, real-time PCR with pathogen-specific molecular beacons (MB) and
      primers was evaluated for prediction of community-acquired pneumonia (CAP)
      causative agents, detecting six main CAP agents, Streptococcus pneumoniae,
      Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae,
      Legionella pneumophila, and Streptococcus pyogenes, simultaneously. The PCR assay
      was evaluated for fresh clinical specimens from infants and children (n = 389)
      and from adults (n = 40). The MB probes and primers are both pathogen specific,
      namely, the lytA gene for S. pneumoniae, the mip gene for L. pneumophila, and 16S
      rRNA genes for the remaining four organisms. DNA extraction of clinical specimens
      was performed with a commercially available EXTRAGEN II kit, and amplification
      was performed with Stratagene Mx3000P. The limit of detection for these pathogens
      ranged from 2 copies to 18 copies. The whole process from DNA extraction to the
      analysis was finished in less than 2 h. The obtained sensitivity and specificity
      of this real-time PCR study relative to those of conventional cultures were as
      follows: 96.2% and 93.2% for S. pneumoniae, 95.8% and 95.4% for H. influenzae,
      100% and 100% for S. pyogenes, and 100% and 95.4% for M. pneumoniae,
      respectively. The sensitivity and specificity for M. pneumoniae relative to those
      of a serologic assay were 90.2% and 97.9%, respectively. In six clinical samples
      of C. pneumoniae, the real-time PCR gave positive predictable values, and in
      those cases, elevation of the titer value was also observed. In conclusion, we
      demonstrated that a real-time PCR assay with pathogen-specific MB is useful in
      identifying CAP causative agents rapidly and in examining the clinical course of
      empirical chemotherapy in a timely manner, supporting conventional culture
      methods.

PMID- 16597875
TI  - Use of a serotype-specific DNA microarray for identification of group B
      Streptococcus (Streptococcus agalactiae).
AB  - Group B Streptococcus (GBS; Streptococcus agalactiae) is an important cause of
      sepsis and meningitis. Nine GBS serotypes, based on capsular polysaccharide (CPS)
      antigens, have been described. Their distribution varies worldwide and needs to
      be monitored to understand the epidemiology of GBS disease and inform the
      development of vaccines. In this study, we sequenced cpsH of GBS serotype II
      (cpsHII) and compared it with that of the other eight serotypes to identify
      serotype-specific regions. We then developed a DNA microarray based on the cpsH
      gene and used it to test 88 GBS isolates-9 serotype reference strains and 79
      clinical isolates-and 7 other bacterial and fungal species which are commonly
      present in the vagina flora. The microarray was shown to be specific and
      reproducible. This is the first report of a microarray which can identify the
      nine GBS serotypes. The use of a microarray has advantages over traditional
      serotyping methods and will be of practical value in both reference and
      diagnostic laboratories.

PMID- 16597876
TI  - Can the fliC PCR-restriction fragment length polymorphism technique replace
      classic serotyping methods for characterizing the H antigen of enterotoxigenic
      Escherichia coli strains?
AB  - In this study, we performed fliC PCR-restriction fragment length polymorphism
      (RFLP) to investigate whether this technique would be better than classic
      serotyping for the characterization of the H antigen in enterotoxigenic
      Escherichia coli (ETEC) strains. We showed that the fliC genes from ETEC strains
      can be characterized by restriction analysis of their polymorphism. Only one
      allele of the fliC gene from ETEC strains was found for each flagellar antigen,
      with the exception of H21. Nonmotile strains could also be characterized using
      this molecular technique. Moreover, determination of the somatic antigen was
      guided by the identification of the flagellar antigen from previously unknown
      serotypes of ETEC strains by PCR-RFLP, thus reducing the number of anti-antigen O
      sera used. The PCR-RFLP technique proved to be faster than classic serotyping for
      the characterization of the E. coli H antigen, taking 2 days to complete instead
      of the 7 or more days using classic serotyping. In conclusion, the H molecular
      typing for Enterobacteriaceae members may become an important epidemiological
      tool for the characterization of the H antigen of E. coli pathotypes. The PCR
      RFLP technique is capable of guiding the determination of the H antigen and could
      partially replace seroagglutination. With the determination of the molecular
      profiles of alleles from strains obtained in epidemiological studies, new
      patterns will be described for ETEC strains or other E. coli pathotypes, thus
      permitting widespread use of this technique to characterize fliC genes and
      determine the H antigen of E. coli strains.

PMID- 16597878
TI  - Relationship of phylogenetic background, biofilm production, and time to
      detection of growth in blood culture vials with clinical variables and prognosis
      associated with Escherichia coli bacteremia.
AB  - In patients with Escherichia coli bacteremia, data on the relationship of
      phylogenetic background, biofilm production, and degree of bacteremia with
      clinical variables and prognosis are scarce. During a 1-year period, all adults
      with bacteremia due to Escherichia coli diagnosed at a university center were
      enrolled. Determination of phylogenetic background, biofilm production, and
      genotyping was performed with all strains, and the time to positivity of blood
      culture vials was recorded. A total of 185 episodes of diverse-source E. coli
      bacteremia was analyzed. Strains of phylogroup D were predominant (52%).
      Phylogroup A isolates were associated with pneumonia and prior antibiotic intake,
      B1 with an abdominal source of infection, B2 with the absence of urological
      abnormalities, and D with urological abnormalities and age below 65 years.
      Resistance to antibiotics and no biofilm production were concentrated in
      phylogroup A strains. Biofilm production was not associated with any clinical
      variable. An immunocompromising condition (odds ratio [OR] = 5.01, 95% confidence
      interval [CI] = 1.4 to 17.9), peritonitis (OR = 17, 95% CI = 3.32 to 87),
      pneumonia (OR = 9.97, 95% CI = 1.96 to 50.6), and </=7 h to bacteremia detection
      (OR = 4.37, 95% CI = 1.38 to 13.8) were the best predictors of a fatal outcome.
      Results from this study suggest that the distribution of phylogenetic backgrounds
      among E. coli strains involved in diverse-source bacteremia may be subject to
      geographical variation and that, in afflicted individuals, some high-risk
      sources, the patient's underlying condition, and the degree of bacteremia are
      more important than microbial factors in determining the outcome. Time to
      positivity of blood culture vials may be a variable of potential clinical impact.

PMID- 16597877
TI  - Single-assay combination of Epstein-Barr Virus (EBV) EBNA1- and viral capsid
      antigen-p18-derived synthetic peptides for measuring anti-EBV immunoglobulin G
      (IgG) and IgA antibody levels in sera from nasopharyngeal carcinoma patients:
      options for field screening.
AB  - Assessment of immunoglobulin A (IgA) antibody responses to various Epstein-Barr
      virus (EBV) antigen complexes, usually involving multiple serological assays, is
      important for the early diagnosis of nasopharyngeal carcinoma (NPC). Through
      combination of two synthetic peptides representing immunodominant epitopes of
      EBNA1 and viral capsid antigen (VCA)-p18 we developed a one-step sandwich enzyme
      linked immunosorbent assay (ELISA) for the specific detection of EBV reactive IgG
      and IgA antibodies in NPC patients (EBV IgG/IgA ELISA). Sera were obtained from
      healthy donors (n = 367), non-NPC head and neck cancer patients (n = 43), and
      biopsy-proven NPC patients (n = 296) of Indonesian and Chinese origin. Higher
      values of optical density at 450 nm for EBV IgG were observed in NPC patients
      compared to the healthy EBV carriers, but the large overlap limits its use for
      NPC diagnosis. Using either EBNA1 or VCA-p18 peptides alone IgA ELISA correctly
      identified 88.5% and 79.8% of Indonesian NPC patients, with specificities of
      80.1% and 70.9%, whereas combined single-well coating with both peptides yielded
      sensitivity and specificity values of 90.1 and 85.4%, respectively. The positive
      and negative predictive values (PPV and NPV, respectively) for the combined EBNA1
      plus VCA EBV IgA ELISA were 78.7% and 93.9%, respectively. In the Indonesia
      panel, the level of EBV IgA reactivity was not associated with NPC tumor size,
      lymph node involvement, and metastasis stage, sex, and age group. In the China
      panel the sensitivity/specificity values were 86.2/92.0% (EBNA1 IgA) and
      84.1/90.3% (VCA-p18 IgA) for single-peptide assays and 95.1/90.6% for the
      combined VCA plus EBNA1 IgA ELISA, with a PPV and an NPV for the combined EBV IgA
      ELISA of 95.6 and 89.3%, respectively. Virtually all NPC patients had abnormal
      anti-EBV IgG diversity patterns as determined by immunoblot analysis. On the
      other hand, healthy EBV carriers with positive EBV IgA ELISA result showed normal
      IgG diversity patterns. By using EBV IgG immunoblot diversity as confirmation
      assay for EBV IgA ELISA-positive samples, the sensitivity and specificity for NPC
      diagnosis increased to 98% and 99.2%, respectively, in the Indonesian NPC
      samples. The use of these combined methods for seroepidemiological screening
      studies is proposed.

PMID- 16597879
TI  - Transmission of an uncultivated Bergeyella strain from the oral cavity to
      amniotic fluid in a case of preterm birth.
AB  - Intrauterine infection is a recognized cause of preterm birth. The infectious
      organisms are believed to originate primarily from the vaginal tract and
      secondarily from other parts of the body. It is plausible that microbes in the
      oral cavity can be transmitted to the pregnant uterus. However, direct evidence
      supporting such a transmission is lacking. In this study, amniotic fluids of 34
      pregnant women were examined by PCR using 16S and 23S rRNA universally conserved
      primers. Bacterial DNA was amplified from the only patient with clinical
      intrauterine infection and histologic necrotizing acute and chronic
      chorioamnionitis. One strain, Bergeyella sp. clone AF14, was detected and was
      99.7% identical to a previously reported uncultivated oral Bergeyella strain,
      clone AK152, at the 16S rRNA level. The same strain was detected in the
      subgingival plaque of the patient but not in her vaginal tract. The 16S-23S rRNA
      sequence of clone AF14 matched exactly with the sequences amplified from the
      patient's subgingival plaque. These observations suggest that the Bergeyella
      strain identified in the patient's intrauterine infection originated from the
      oral cavity. This is the first direct evidence of oral-utero microbial
      transmission. The patient's periodontal health during pregnancy was unclear. She
      did not have detectable periodontal disease during postpartum examination.
      Bergeyella spp. had not been previously associated with preterm birth and were
      detected in subgingival plaque of women without clinical levels of intrauterine
      infection. Uncultivated species may be overlooked opportunistic pathogens in
      preterm birth. This study sheds new light on the implication of oral bacteria in
      preterm birth.

PMID- 16597880
TI  - Characterization of human metapneumovirus infections in Israel.
AB  - Respiratory tract infections are a leading cause of morbidity and mortality
      worldwide. Even with the advancement of diagnostic tools, the causative agent of
      20 to 30% of upper respiratory tract infections go undiagnosed. Recently, a newly
      identified human respiratory virus, human metapneumovirus (hMPV), was discovered
      in young children in The Netherlands. To study the prevalence of hMPV infections
      in Israeli children, respiratory specimens from 388 hospitalized children less
      than 5 years of age were evaluated for the presence of hMPV RNA, which was
      present in 42 (10.8%) of these samples. All hMPV-positive samples were negative
      for respiratory syncytial virus (RSV), influenza viruses (Flu) A and B,
      adenovirus, and parainfluenza viruses 1, 2, and 3. Conversely, hMPV RNA was not
      detected in 76 RSV-positive and 38 Flu A- or B-positive samples. Most hMPV
      activity was between the months February and April. Sequence analysis of 20
      positive samples revealed that both of the hMPV genotypes (groups 1 and 2) have
      circulated in central Israel during the study period. Moreover, three of the four
      known hMPV subgroups (1A, 1B, and 2B) were detected among the tested samples.
      Seroprevalence of hMPV in 204 patients from the central part of Israel revealed
      that 100% of the children are hMPV seropositive by the age of 5 years old. We
      conclude that hMPV is a common respiratory pathogen in Israel, while mixed
      infections of hMPV with RSV or Flu in hospitalized children are apparently rare.

PMID- 16597881
TI  - Quantification of hepatitis B virus (HBV) DNA with a TaqMan HBV analyte-specific
      reagent following sample processing with the MagNA pure LC instrument.
AB  - TaqMan hepatitis B virus (HBV) analyte-specific reagent (ASR; Roche Molecular
      Systems, Inc., Branchburg, NJ) is designed for the quantification of HBV DNA in
      serum or plasma. The performance characteristics of TaqMan HBV ASR following
      automated sample processing with the MagNA Pure LC instrument (MP; Roche Applied
      Science, Indianapolis, IN) were evaluated in this study. Analytical sensitivity
      and precision were assessed with commercially available HBV standards, while
      clinical serum specimens from HBsAg-seropositive patients and healthy blood
      donors were used to determine clinical sensitivity, specificity, and correlation
      with other commercially available assays. Analytical studies yielded a limit of
      detection of 2.4 IU/ml, with good linearity and correlation (R(2) = 0.9958) with
      expected HBV DNA titers over a wide range (6.0 x 10(0) to 2.1 x 10(8) IU/ml).
      Clinical sensitivity and specificity of the assay combined with automated sample
      processing were both 100%. Comparison of TaqMan HBV ASR and VERSANT HBV DNA 3.0
      assay (bDNA; Bayer HealthCare LLC, Tarrytown, NY) results among clinical
      specimens yielded good correlation (R(2) = 0.9237), with a mean difference in
      titer of -0.213 log(10) IU/ml (95% confidence interval, -0.678 to 1.10 log(10)
      IU/ml). The overall test failure rate was 2.0% among 204 clinical serum specimens
      tested. Total time required for MP sample processing and automated postelution
      handling of 24 samples was 224 min, with 57 min of actual hands-on time. MP is a
      reliable, labor-saving platform suitable for use with TaqMan HBV ASR, providing
      sensitive and accurate quantification of HBV DNA levels over a range of 8 log(10)
      IU/ml.

PMID- 16597883
TI  - Isothermal amplification and molecular typing of the obligate intracellular
      pathogen Mycobacterium leprae isolated from tissues of unknown origins.
AB  - Molecular diagnostic and epidemiology studies require appreciable amounts of high
      quality DNA. Molecular epidemiologic methods have not been routinely applied to
      the obligate intracellular organism Mycobacterium leprae because of the
      difficulty of obtaining a genomic DNA template from clinical material.
      Accordingly, we have developed a method based on isothermic multiple-displacement
      amplification to allow access to a high-quality DNA template. In the study
      described in this report, we evaluated the usefulness of this method for error
      sensitive, multiple-feature molecular analyses. Using test samples isolated from
      lepromatous tissue, we also evaluated amplification fidelity, genome coverage,
      and regional amplification bias. The fidelity of amplified genomic material was
      unaltered; and while regional differences in global amplification efficiency were
      seen by using comparative microarray analysis, a high degree of concordance of
      amplified genomic DNA was observed. This method was also applied directly to
      archived tissue specimens from leprosy patients for the purpose of molecular
      typing by using short tandem repeats; the success rate was increased from 25% to
      92% without the introduction of errors. This is the first study to demonstrate
      that serial whole-genome amplification can be coupled with error-sensitive
      molecular typing methods with low-copy-number sequences from tissues containing
      an obligate intracellular pathogen.

PMID- 16597882
TI  - Differentiation of Escherichia coli pathotypes by oligonucleotide spotted array.
AB  - To accurately determine the pathotypes of Escherichia coli strains, a
      comprehensive assessment of each strain that targets multiple genes is required.
      A new approach to the identification and characterization of E. coli pathotypes
      was developed by constructing gene-specific probes (70-mers) for not only the
      virulence genes associated with each E. coli pathotype but also the O157-, CFT073
      , and K-12-specific and common genes of each pathotype. Analysis of
      oligonucleotide probes with reference and clinical isolates of E. coli pathotypes
      indicated that the array could differentiate the pathotypes on the basis of their
      virulence and specific gene patterns. Probes targeting common genes of E. coli
      were present in all the reference and clinical strains. Salmonella enterica
      subsp. enterica-specific genes and Salmonella core genes were used as negative
      controls. The entire E. coli pathotype showed reactivity to only 4 of the 81
      Salmonella-specific gene probes. Characterization of the genetic and virulence
      profiles of a single strain by using probes for virulence factors and specific
      and common genes in the spotted array is an ideal diagnostic tool for
      determination of E. coli pathotypes and could also have a significant impact on
      the epidemiological analysis of E. coli infections.

PMID- 16597884
TI  - Multiple-locus variable-number tandem repeat analysis of Neisseria meningitidis
      yields groupings similar to those obtained by multilocus sequence typing.
AB  - We identified many variable-number tandem repeat (VNTR) loci in the genomes of
      Neisseria meningitidis serogroups A, B, and C and utilized a number of these loci
      to develop a multiple-locus variable-number tandem repeat analysis (MLVA). Eighty
      five N. meningitidis serogroup B and C isolates obtained from Dutch patients with
      invasive meningococcal disease and seven reference strains were analyzed using
      MLVA and multilocus sequence typing (MLST). MLVA, based on eight VNTR loci with
      limited variability in the number of repeats, yielded clustering of the strains
      similar to that obtained by MLST, with congruence between both methods amounting
      to 69%. The ability to recognize clonal complexes makes MLVA a valuable high
      throughput method to serve as a tool complementary to MLST. Four highly variable
      VNTR loci were used in a second assay to analyze N. meningitidis serogroup C
      strains collected during an outbreak of meningococcal disease in The Netherlands.
      Typing based on the latter VNTR loci enabled differentiation of isolates with
      identical MLST sequence types and grouped epidemiologically related strains.

PMID- 16597886
TI  - Invasive Haemophilus influenzae in Manitoba, Canada, in the postvaccination era.
AB  - Fifty-two Haemophilus influenzae isolates from patients with invasive disease in
      the province of Manitoba, Canada, were examined for serotype, biotype, genotype,
      and antibiotic susceptibility. Half of the 52 isolates were found to be serotype
      a, and 38.5% (20 isolates) were found to be nonserotypeable (NST). There were
      only three serotype b strains and one each for serotypes c, d, and f. All 26
      serotype a isolates belonged to biotype II and demonstrated identical or highly
      similar DNA fingerprints by pulsed-field gel electrophoresis. An analysis of
      these isolates by multilocus sequence typing showed that they belong to the
      clonal complex ST-23. While 69% (18 of 26) of the serotype a cases were found in
      males, only 9 (45%) of the 20 patients with NST isolates were males. Twenty (77%)
      of the 26 serotype a isolates were from patients who were </=24 months old.
      Twelve (63%) of the NST isolates were from adult or adolescent patients. In
      contrast to the clonal nature of serotype a isolates, the 20 NST isolates were
      found to belong to 18 different sequence types. Most of these 18 different
      sequence types were unrelated to each other, with the exception of 7 sequence
      types grouped into three clonal groups. Two (6.25%) out of 32 serotypeable
      isolates (1 serotype a and 1 serotype b) and 6 (30%) of 20 NST isolates were
      resistant to ampicillin due to beta-lactamase production. These results suggest a
      change in the epidemiology of H. influenzae disease, with the majority of
      invasive H. influenzae isolates being associated with serotype a and NST strains.

PMID- 16597885
TI  - Use of a short fragment of the C-terminal E gene for detection and
      characterization of two new lineages of dengue virus 1 in India.
AB  - Here we propose the use of a 216-nucleotide fragment located in the carboxyl
      terminus of the E gene (E-COOH) and a pairwise-based comparison method for
      genotyping of dengue virus 1 (DENV-1) strains. We have applied this method to the
      detection and characterization of DENV-1 in serum samples from travelers
      returning from the tropics. The results obtained with the typing system correlate
      with the results obtained by comparison of the sequences of the entire E gene of
      the strains. The approach demonstrates utility in plotting the distribution and
      circulation of different genotypes of DENV-1 and also suggests the presence of
      two new clades of Indian strains. The integration of the method with an online
      database and a typing characterization tool enhances its strength. Additionally,
      the analysis of the complete E gene of DENV-1 strains suggested the occurrence of
      a nondescribed recombination event in the China GD23-95 strain. We propose the
      use of this methodology as a tool for real-time epidemiological surveillance of
      dengue virus infections and their pathogenesis.

PMID- 16597887
TI  - Phenotypic switching in Candida lusitaniae on copper sulfate indicator agar:
      association with amphotericin B resistance and filamentation.
AB  - Candida lusitaniae is an opportunistic yeast pathogen that has the ability to
      develop resistance to amphotericin B (AmB). The mechanism(s) for this resistance
      is not well understood, although there are data supporting mutations in sterol
      pathways and other data supporting phenotypic switching (PS). The goal of this
      study was to determine whether C. lusitaniae has a PS system and to characterize
      any phenotypes, including any changes in AmB MICs. When 10(4) CFU of an AmB
      resistant (MIC of 16 to 32 microg/ml) clinical strain was plated on yeast-peptone
      dextrose (YPD) agar with 1 mM CuSO(4), three colony colors were observed: light
      brown (LB) >> dark brown (DB) > white (W), similar to the result for Candida
      glabrata. Switching did occur with high AmB resistance (MIC of 256 microg/ml)
      being associated with W, whereas LB and DB colonies had MICs of 2 to 8 microg/ml
      and 2 to 16 microg/ml, respectively. Filamentation (pseudohyphae) was associated
      with DB colonies. All phenotypes occurred spontaneously with greater frequency (
      approximately 10(-2) to 10(-4)) than spontaneous mutations, and all phenotypes
      were reversible, fulfilling the two PS criteria. High AmB MICs were always
      associated with W colonies but not with all W colonies. Detection of PS on YPD
      CuSO(4) is also similar to that in Candida glabrata, and we hypothesize that this
      is due to similarities in metallothionein gene expression. Phenotypic switching
      represents a key strategy in C. lusitaniae that confers a selective advantage
      during environmental challenges, including the ability to switch to AmB
      resistance.

PMID- 16597888
TI  - A sensor to detect the early stages in the development of crystalline Proteus
      mirabilis biofilm on indwelling bladder catheters.
AB  - A simple sensor has been developed to detect the early stages of urinary catheter
      encrustation and avoid the clinical crises induced by catheter blockage. In
      laboratory models of colonization by Proteus mirabilis, the sensor signaled
      encrustation at an average time of 43 h before catheters were blocked with
      crystalline biofilm.

PMID- 16597889
TI  - Molecular investigation of human immunodeficiency virus type 2 subtype a cases in
      South Korea.
AB  - We investigated the molecular characteristics of human immunodeficiency virus
      type 2 (HIV-2) subtype A isolates to clarify the transmission mode of HIV-2
      within Korea. These findings indicated that the viruses from the six patients
      infected within Korea formed a distinct subcluster in the phylogenetic tree and
      might have been transmitted from one source.

PMID- 16597890
TI  - Compliance of clinical microbiology laboratories in the United States with
      current recommendations for processing respiratory tract specimens from patients
      with cystic fibrosis.
AB  - Respiratory tract specimens from patients with cystic fibrosis (CF) require
      unique processing by clinical microbiology laboratories to ensure detection of
      all potential pathogens. The present study sought to determine the compliance of
      microbiology laboratories in the United States with recently published
      recommendations for CF respiratory specimens. Microbiology laboratory protocols
      from 150 of 190 (79%) CF care sites were reviewed. Most described the use of
      selective media for Burkholderia cepacia complex (99%), Staphylococcus aureus
      (82%), and Haemophilus influenzae (89%) and identified the species of all gram
      negative bacilli (87%). Only 52% delineated the use of agar diffusion assays for
      susceptibility testing of Pseudomonas aeruginosa. Standardizing laboratory
      practices will improve treatment, infection control, and our understanding of the
      changing epidemiology of CF microbiology.

PMID- 16597891
TI  - Seroprevalence and molecular epidemiology of human T-Cell leukemia virus type 1
      (HTLV-1) and HTLV-2 in blood donors from Dakar, Senegal.
AB  - In 2002, human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 seroprevalence
      was 0.16% (8/4,900) in blood donors from Dakar, Senegal. Most of the positive
      donors originated from the country's southern region. Seven donors were infected
      by HTLV-1 (of cosmopolitan subtype), and one was infected by HTLV-2. These data
      highlight the problem of transfusion safety in this area where HTLV-1-associated
      lymphoproliferative and neurological diseases are endemic.

PMID- 16597892
TI  - Clonal distribution and differential occurrence of the enterotoxin gene cluster,
      egc, in carriage- versus bacteremia-associated isolates of Staphylococcus aureus.
AB  - The Staphylococcus aureus enterotoxin gene cluster, egc, was detected in isolates
      from healthy individuals and in those from patients with bacteremia. The egc
      genes cooccur and are slightly enriched in strains from healthy carriers (present
      in 63.7% of carriage-associated isolates versus 52.9% of invasive isolates; P =
      0.03). Multilocus sequence typing revealed that successful staphylococcal clones
      usually harbor the egc locus.

PMID- 16597893
TI  - Microevolution of the direct repeat locus of Mycobacterium tuberculosis in a
      strain prevalent in San Francisco.
AB  - We describe a microevolutionary event of a prevalent strain of Mycobacterium
      tuberculosis that caused two outbreaks in San Francisco. During the second
      outbreak, a direct variable repeat was lost. We discuss the mechanisms of this
      change and the implications of analyzing multiple genetic loci in this context.

PMID- 16597894
TI  - Early detection of hepatitis C virus infection by use of a new combined antigen
      antibody detection assay: potential use for high-risk individuals.
AB  - The performance of a new combined antigen-antibody assay (Monolisa HCV Ag-Ab
      Ultra; Bio-Rad Laboratories) was evaluated in the context of acute hepatitis C in
      human immunodeficiency virus-infected patients. The combined assay became
      positive as early as the first PCR and earlier than a third-generation enzyme
      linked immunosorbent assay in 65% of the cases. Reduction of the long period of
      HCV seronegativity should improve the diagnosis of hepatitis C infection,
      especially in high-risk populations.

PMID- 16597895
TI  - Discovery of the neutralizing epitope common to influenza B virus victoria group
      isolates in Japan.
AB  - Monoclonal antibody 9B2 possesses hemagglutination inhibition activity against
      all the 2002/2003 influenza B virus Victoria group isolates in Kobe, Japan, as
      well as representative strains isolated between 1987 and 1997. The 9B2 epitope
      localizes three-dimensionally in the vicinity of antigenic site A of the
      hemagglutinin molecule, and amino acid substitutions in this region affected the
      binding of 9B2.

PMID- 16597896
TI  - Rapid identification of Enterococcus hirae and Enterococcus durans by PCR and
      detection of a homologue of the E. hirae mur-2 Gene in E. durans.
AB  - During an evaluation of PCR for identification of isolates of Enterococcus hirae,
      a homologue with 82% identity to E. hirae mur-2 was identified in Enterococcus
      durans and was named mur-2(ed). PCR using primers for two genes (copY and murG)
      of E. hirae strains showed amplification with E. hirae strains only. PCR (under
      high-stringency conditions) with primers for the mur-2(ed) gene gave the expected
      amplification product only with E. durans strains. A combination of murG and mur
      2(ed) primers in a multiplex PCR assay differentiated E. hirae from E. durans in
      all cases. PCR using these primers appears to be a rapid alternative for
      identification of E. hirae and E. durans isolates.

PMID- 16597897
TI  - Human herpesvirus 6 chromosomal integration in immunocompetent patients results
      in high levels of viral DNA in blood, sera, and hair follicles.
AB  - Six immunocompetent patients with human herpesvirus 6 (HHV-6) chromosomal
      integration had HHV-6 and beta-globin DNA quantified in various samples by PCR.
      The mean HHV-6 DNA concentration (log(10) copies/milliliter) in blood was 7.0
      (>/=1 HHV-6 DNA copies/leukocyte), and in serum it was 5.3 (>/=1 HHV-6 DNA
      copies/lysed cell). The mean HHV-6 DNA load (log(10) copies)/hair follicle was
      4.2 (>/=1 copies/hair follicle cell), demonstrating that viral integration is not
      confined to blood cells. The characteristically high HHV-6 DNA levels in
      chromosomal integration may confound laboratory diagnosis of HHV-6 infection and
      should be given due consideration.

PMID- 16597898
TI  - Molecular characterization and drug resistance testing of Mycobacterium
      tuberculosis isolates from Chad.
AB  - The molecular characterizations of the first 40 Mycobacterium tuberculosis
      isolates from Chad revealed a high proportion of isolates of the Cameroon family
      (33%), of which one isolate showed a monodrug resistance. In total, 9/33 (27%)
      isolates were resistant to isoniazid. The implications of these findings are
      discussed.

PMID- 16597899
TI  - A 24-hour screening protocol for identification of vancomycin-resistant
      Enterococcus faecium.
AB  - We describe a 24-h protocol for the identification of patients who are positive
      for vancomycin-resistant Enterococcus faecium (VRE), using stool and rectal swab
      samples and VRE screening broth, automated DNA extraction, and real-time PCR for
      vanA and vanB genes. Compared to conventional screening methods, this protocol
      had a high sensitivity and specificity and a negative predictive value.

PMID- 16597900
TI  - Evaluation of diagnostic assays for hepatitis E virus in outbreak settings.
AB  - Hepatitis E virus (HEV) is a major cause of hepatitis. We evaluated five HEV
      antibody diagnostic assays by using outbreak specimens. The Abbott immunoglobulin
      G (IgG), Genelabs IgG, and Walter Reed Army Institute of Research (WRAIR) IgM
      assays were about 90% sensitive; the Abbott IgG and WRAIR total Ig and IgM assays
      were more than 90% specific.

PMID- 16597901
TI  - Fulminant, acyclovir-resistant, herpes simplex virus type 2 hepatitis in an
      immunocompetent woman.
AB  - We report an immunocompetent woman with multisystem organ failure following
      herpes simplex virus type 2 (HSV-2) hepatitis. After she initially responded to
      intravenous acyclovir, she was switched to oral valacyclovir. She developed
      respiratory failure and opportunistic infections and died. Autopsy confirmed
      disseminated HSV infection, and lung tissue grew acyclovir-resistant HSV-2.

PMID- 16597902
TI  - Nosocomial bacteremia due to an as yet unclassified acinetobacter genomic species
      17-like strain.
AB  - We describe a case of bacteremia due to an as yet unclassified Acinetobacter
      genomic species 17-like strain. The recognition of this microorganism as non
      Acinetobacter baumannii may have important epidemiological implications, as it
      relieves the hospital of the implementation of barrier precautions for patients
      infected or colonized as may be necessary with a multiresistant A. baumannii
      epidemic.

PMID- 16597903
TI  - Fluoroquinolone resistance in Ureaplasma parvum in the United States.
AB  - We report the first case of naturally occurring fluoroquinolone resistance in
      Ureaplasma spp. from the United States. Resistance in this case probably
      developed as a result of mutations in the gyrA and parC genes of the DNA
      gyrase/topoisomerase IV complex that occurred in the presence of antimicrobial
      selective pressure.

PMID- 16597904
TI  - Surveillance of antimicrobial resistance in Neisseria meningitidis from patients
      in the Cincinnati tristate region (Ohio, Kentucky, and Indiana).

PMID- 16597905
TI  - Inactivation of cultured Mycobacterium tuberculosis organisms prior to DNA
      extraction.

PMID- 16597906
TI  - Performance of rapid tests for detection of avian influenza A virus types H5N1
      and H9N2.

PMID- 16597907
TI  - BioRobot EZ1 workstation compares well with manual spin kits for extraction of
      viral RNA from sera and saves substantial staff time.

PMID- 16597908
TI  - Discordant results of two automated assays for detection of hepatitis C virus
      specific antibody.

PMID- 16597909
TI  - Use of galactomannan enzyme immunoassay for diagnosis of invasive aspergillosis
      in a tertiary-care center over a 12-month period.

PMID- 16597910
TI  - Broad differences between the COBAS ampliprep total nucleic acid isolation-COBAS
      TaqMan 48 hepatitis C virus (HCV) and COBAS HCV monitor v2.0 assays for
      quantification of serum HCV RNA of non-1 genotypes.

PMID- 16597911
TI  - Rapid molecular detection of methicillin-resistant Staphylococcus aureus.

PMID- 16597912
TI  - Some Bacillus thuringiensis strains share rpoB nucleotide polymorphisms also
      present in Bacillus anthracis.

PMID- 16597913
TI  - Saaremaa hantavirus should not be confused with its dangerous relative, Dobrava
      virus.

PMID- 16597914
TI  - Use of mycobacterial interspersed repetitive unit locus 26 for rapid
      identification of Beijing genotype Mycobacterium tuberculosis strains.

PMID- 16597915
TI  - Mycobacterium tuberculosis Beijing genotype and mycobacterial interspersed
      repetitive unit typing.

PMID- 16597916
TI  - Evaluation of tests for Lyme disease.

PMID- 16597917
TI  - Thermosensitive TRP ion channels mediate cytosolic calcium response in human
      synoviocytes.
AB  - The transient receptor potential (TRP) channels are important membrane sensors,
      responding to thermal, chemical, osmotic, or mechanical stimuli by activation of
      calcium and sodium fluxes. In this study, three distinct TRP channels were
      detected and their role established in mediating cytosolic free calcium
      concentration ([Ca(2+)](cyt)) response in tumor-derived SW982 synoviocytes and
      primary cultures of human synovial cells from patients with inflammatory
      arthropathies. As shown by fura-2 ratio measurements while cells were incubated
      in a temperature-regulated chamber, significant [Ca(2+)](cyt) elevation was
      elicited by rapid changes in bath temperature, application of TRPV1 receptor
      agonists capsaicin and resiniferatoxin, or a cold receptor stimulator, icilin.
      Temperature thresholds for calcium response were determined to be 12 +/- 1
      degrees C for cold and 28 +/- 2 degrees C for heat activation. Temperature
      increases or decreases beyond these thresholds resulted in a significant rise in
      the magnitude of [Ca(2+)](cyt) spikes. Observed changes in [Ca(2+)](cyt) were
      completely abolished in calcium-free medium and thus resulted from direct calcium
      entry through TRP channels rather then by activation of voltage-dependent calcium
      channels. Two heat sensitive channels, TRPV1 and TRPV4, and a cold-sensitive
      channel, TRPA1, were detected by RT-PCR. Minimal mRNA for TRPV3 or TRPM8 was
      amplified. The RT-PCR results support the data obtained with the [Ca(2+)](cyt)
      measurements. We propose that the TRP channels are functionally expressed in
      human synoviocytes and may play a critical role in adaptive or pathological
      changes in articular surfaces during arthritic inflammation.

PMID- 16597918
TI  - Mechanism of induction of pancreatic acinar cell apoptosis by hydrogen sulfide.
AB  - The present study investigated the mechanism of mouse pancreatic acinar cell
      apoptosis induced by H(2)S in an in vitro system, using isolated pancreatic
      acini. Treatment of pancreatic acini with 10 microM NaHS (a donor of H(2)S) for 3
      h caused phosphatidylserine externalization as shown by annexin V binding, an
      indicator of early stages of apoptosis. This treatment also resulted in the
      activation of the caspase cascade and major changes at the mitochondrial level.
      Caspase-3, -8, and -9 activities were stimulated by H(2)S treatment. Treatment
      with inhibitors of caspase-3, -8, and -9 significantly inhibited H(2)S-induced
      phosphatidylserine externalization as shown by reduced annexin V staining. The
      mitochondrial membrane potential was collapsed in H(2)S-treated acini as
      evidenced by fluorescence microscopy and quantitative analysis. Furthermore, the
      treatment of acini with H(2)S caused the release of cytochrome c by the
      mitochondria. To investigate the mechanism underlying pancreatic acinar cell
      apoptosis, we also characterized the protein expression of a range of molecules
      that are each known to influence the apoptotic pathway. Among proapoptotic
      proteins, Bax expression was activated in H(2)S-treated cells but not Bid, and
      the antiapoptotic proteins Bcl-X(L) and Bcl-2 did not show any activation in
      pancreatic acinar cell apoptosis. The death effector domain-containing protein
      Flip is downregulated in H(2)S-treated acini. These results demonstrate the
      induction of pancreatic acinar cell apoptosis in vitro by H(2)S and the
      involvement of both mitochondrial and death receptor pathways in the process of
      apoptosis.

PMID- 16597919
TI  - Calcitonin gene-related peptide inhibits interleukin-1beta-induced endogenous
      monocyte chemoattractant protein-1 secretion in type II alveolar epithelial
      cells.
AB  - As important multifunctional cells in the lung, alveolar epithelial type II
      (AEII) cells secrete numerous chemokines on various stimuli. Our previous data
      showed that AEII cells also express the neuropeptide calcitonin gene-related
      peptide (CGRP) and the proinflammatory factor interleukin (IL)-1beta induces CGRP
      secretion in the A549 human AEII cell line. In the present study, the CGRP-1
      receptor antagonist human (h)CGRP(8-37) (0.1-1 nM) greatly amplified the
      production of IL-1beta-induced monocyte chemoattractant protein (MCP)-1. The
      inhibition of CGRP expression by small interfering RNA significantly increased
      MCP-1 secretion on IL-1beta stimulation. However, exogenous hCGRP (10-100 nM)
      suppressed IL-1beta-evoked MCP-1 secretion in MCP-1 promoter activity, and CGRP
      gene stably transfected cell clones significantly inhibited both the mRNA and
      protein levels of MCP-1 induced by IL-1beta. These data imply that AEII-derived
      CGRP suppressed IL-1beta-induced MCP-1 secretion in an autocrine/paracrine mode.
      Subsequent investigation revealed that CGRP inhibited IL-1beta-evoked NF-kappaB
      activity by suppressing IkappaBalpha phosphorylation and degradation. Moreover,
      CGRP attenuated IL-1beta-induced reactive oxygen species (ROS) formation, the
      early event in proinflammatory factor signaling. We previously showed that the
      CGRP inhibitory effect was mediated by elevated intracellular cAMP and show here
      that analogs of cAMP, 8-bromoadenosine 3',5'-cyclic monophosphothioate and the Sp
      isomer of adenosine 3',5'-cyclic monophosphothioate, mimicked the CGRP
      suppressive effect on IL-1beta-induced ROS formation, NF-kappaB activation, and
      MCP-1 secretion. Thus increased endogenous CGRP secretion in lung inflammatory
      disease might eliminate the excessive response by elevating the cAMP level
      through inhibiting the ROS-NF-kappaB-MCP-1 pathway.

PMID- 16597921
TI  - Can activation account for 80% of skeletal muscle energy use during isometric
      contraction?

PMID- 16597920
TI  - Involvement of JAK2 and Src kinase tyrosine phosphorylation in human growth
      hormone-stimulated increases in cytosolic free Ca2+ and insulin secretion.
AB  - We previously reported that human growth hormone (hGH) increases cytoplasmic
      Ca(2+) concentration ([Ca(2+)](i)) and proliferation in pancreatic beta-cells
      (Sjoholm A, Zhang Q, Welsh N, Hansson A, Larsson O, Tally M, and Berggren PO. J
      Biol Chem 275: 21033-21040, 2000) and that the hGH-induced rise in [Ca(2+)](i)
      involves Ca(2+)-induced Ca(2+) release facilitated by tyrosine phosphorylation of
      ryanodine receptors (Zhang Q, Kohler M, Yang SN, Zhang F, Larsson O, and Berggren
      PO. Mol Endocrinol 18: 1658-1669, 2004). Here we investigated the tyrosine
      kinases that convey the hGH-induced rise in [Ca(2+)](i) and insulin release in
      BRIN-BD11 beta-cells. hGH caused tyrosine phosphorylation of Janus kinase (JAK)2
      and c-Src, events inhibited by the JAK2 inhibitor AG490 or the Src kinase
      inhibitor PP2. Although hGH-stimulated rises in [Ca(2+)](i) and insulin secretion
      were completely abolished by AG490 and JAK2 inhibitor II, the inhibitors had no
      effect on insulin secretion stimulated by a high K(+) concentration. Similarly,
      Src kinase inhibitor-1 and PP2, but not its inactive analog PP3, suppressed
      [Ca(2+)](i) elevation and completely abolished insulin secretion stimulated by
      hGH but did not affect responses to K(+). Ovine prolactin increased [Ca(2+)](i)
      and insulin secretion to a similar extent as hGH, effects prevented by the JAK2
      and Src kinase inhibitors. In contrast, bovine GH evoked a rise in [Ca(2+)](i)
      but did not stimulate insulin secretion. Neither JAK2 nor Src kinase inhibitors
      influenced the effect of bovine GH on [Ca(2+)](i). Our study indicates that hGH
      stimulates rise in [Ca(2+)](i) and insulin secretion mainly through activation of
      the prolactin receptor and JAK2 and Src kinases in rat insulin-secreting cells.

PMID- 16597922
TI  - Quorum sensing on a global scale: massive numbers of bioluminescent bacteria make
      milky seas.

PMID- 16597923
TI  - The phosphopantetheinyl transferase superfamily: phylogenetic analysis and
      functional implications in cyanobacteria.
AB  - Phosphopantetheinyl transferases (PPTs) are a superfamily of essential enzymes
      required for the synthesis of a wide range of compounds including fatty acid,
      polyketide, and nonribosomal peptide metabolites. These enzymes activate carrier
      proteins in specific biosynthetic pathways by the transfer of a
      phosphopantetheinyl moiety to an invariant serine residue. PPTs display low
      levels of sequence similarity but can be classified into two major families based
      on several short motifs. The prototype of the first family is the broad-substrate
      range PPT Sfp, which is required for biosynthesis of surfactin in Bacillus
      subtilis. The second family is typified by the Escherichia coli acyl carrier
      protein synthase (AcpS). Facilitated by the growing number of genome sequences
      available for analyses, large-scale phylogenetic studies were utilized in this
      research to reveal novel subfamily groupings, including two subfamilies within
      the Sfp-like family. In the present study degenerate oligonucleotide primers were
      designed for amplification of cyanobacterial PPT gene fragments. Subsequent
      phylogenetic analyses suggested a unique, function-based PPT type, defined by the
      PPTs involved in heterocyst differentiation. Evidence supporting this hypothesis
      was obtained by sequencing the region surrounding the partial Nodularia spumigena
      PPT gene. The ability to genetically classify PPT function is critical for the
      engineering of novel compounds utilizing combinatorial biosynthesis techniques.
      Information regarding cyanobacterial PPTs has important ramifications for the ex
      situ production of cyanobacterial natural products.

PMID- 16597924
TI  - Inhibition of epsilon-poly-L-lysine biosynthesis in Streptomycetaceae bacteria by
      short-chain polyols.
AB  - Antimicrobial epsilon-poly-L-lysine (ePL) is secreted by Streptomycetaceae
      bacteria, and the mechanism of ePL biosynthesis remains to be elucidated. We
      previously reported that an unknown ePL derivative accumulates in the culture
      medium of ePL-producing bacteria when glycerol is added to the culture medium
      (Nishikawa and Ogawa, Appl. Environ. Microbiol. 68:3575-3581, 2002). In this
      study, by using matrix-assisted laser desorption ionization-time of flight mass
      spectrometry and nuclear magnetic resonance, we identified the unknown derivative
      as the ester formed between the hydroxyl group of a glycerol molecule and the
      terminal carboxyl group of an ePL molecule. When a short-chain aliphatic polyol,
      such as ethylene glycol, propanediol, or butanediol, was added instead of
      glycerol, a corresponding ePL-polyol monoester accumulated in the culture medium
      of ePL-producing bacteria. ePL esterification was accompanied by ePL synthesis in
      intact cells and a cell-free system, but no esterification of exogenous ePL was
      observed. ePL-polyol esters were formed during lysine polymerization. The number
      of lysine residues of ePL-polyol esters decreased with increasing polyol
      concentration. Taken together, these results indicate that ePL synthesis is
      inhibited by polyols via esterification and that ePL elongation occurs via the
      incorporation of lysine monomers into the carboxyl terminus of ePL.

PMID- 16597925
TI  - Construction and analysis of fractional multifactorial designs to study
      attachment strength and transfer of Listeria monocytogenes from pure or mixed
      biofilms after contact with a solid model food.
AB  - The aim of this study was to establish which of seven factors influence the
      adhesion strength and hence bacterial transfer between biofilms containing
      Listeria monocytogenes (pure and two-species biofilms) and tryptone soya agar
      (TSA) as a solid organic surface. The two-species biofilms were made of L.
      monocytogenes and one of the following species of bacteria: the nonpathogenic
      organisms Kocuria varians, Pseudomonas fluorescens, and Staphylococcus sciuri and
      CCL 63, an unidentified gram-negative bacterium isolated from the processing
      plant environment. We used biofilms prepared under conditions simulating open
      surfaces in meat-processing sites. The biofilm's adhesion strength and population
      were evaluated by making 12 contacts on a given whole biofilm (4.5 cm(2)), using
      a new slice of a sterilized TSA cylinder for each contact, and plotting the
      logarithm CFU . cm(-2) detached by each contact against the contact number. Three
      types of detachment kinetics were observed: biphasic kinetics, where the first
      slope may be either positive or negative, and monophasic kinetics. The bacteria
      that resisted a chlorinated alkaline product and a glutaraldehyde- and quaternary
      ammonium-based disinfectant had greater adhesion strengths than those determined
      for untreated biofilms. One of the four non-Listeria strains studied, Kocuria
      varians CCL 56, favored both the attachment and detachment of L. monocytogenes.
      The stainless steel had smaller bacterial populations than polymer materials, and
      non-Listeria bacteria adhered to it less strongly. Our results helped to evaluate
      measures aimed at controlling the immediate risk, linked to the presence of a
      large number of CFU in a foodstuff, and the delayed risk, linked to the
      persistence of L. monocytogenes and the occurrence of slightly contaminated foods
      that may become dangerous if L. monocytogenes multiplies during storage. Cleaning
      and disinfection reduce the immediate risk, while reducing the delayed risk
      should be achieved by lowering the adhesion strength, which the sanitizers used
      here cannot do at low concentrations.

PMID- 16597926
TI  - rRNA and poly-beta-hydroxybutyrate dynamics in bioreactors subjected to feast and
      famine cycles.
AB  - Feast and famine cycles are common in activated sludge wastewater treatment
      systems, and they select for bacteria that accumulate storage compounds, such as
      poly-beta-hydroxybutyrate (PHB). Previous studies have shown that variations in
      influent substrate concentrations force bacteria to accumulate high levels of
      rRNA compared to the levels in bacteria grown in chemostats. Therefore, it can be
      hypothesized that bacteria accumulate more rRNA when they are subjected to feast
      and famine cycles. However, PHB-accumulating bacteria can form biomass (grow)
      throughout a feast and famine cycle and thus have a lower peak biomass formation
      rate during the cycle. Consequently, PHB-accumulating bacteria may accumulate
      less rRNA when they are subjected to feast and famine cycles than bacteria that
      are not capable of PHB accumulation. These hypotheses were tested with Wautersia
      eutropha H16 (wild type) and W. eutropha PHB-4 (a mutant not capable of
      accumulating PHB) grown in chemostat and semibatch reactors. For both strains,
      the cellular RNA level was higher when the organism was grown in semibatch
      reactors than when it was grown in chemostats, and the specific biomass formation
      rates during the feast phase were linearly related to the cellular RNA levels for
      cultures. Although the two strains exhibited maximum uptake rates when they were
      grown in semibatch reactors, the wild-type strain responded much more rapidly to
      the addition of fresh medium than the mutant responded. Furthermore, the
      chemostat-grown mutant culture was unable to exhibit maximum substrate uptake
      rates when it was subjected to pulse-wise addition of fresh medium. These data
      show that the ability to accumulate PHB does not prevent bacteria from
      accumulating high levels of rRNA when they are subjected to feast and famine
      cycles. Our results also demonstrate that the ability to accumulate PHB makes the
      bacteria more responsive to sudden increases in substrate concentrations, which
      explains their ecological advantage.

PMID- 16597927
TI  - Polychlorinated biphenyl (PCB)-degrading bacteria associated with trees in a PCB
      contaminated site.
AB  - The abundance, identities, and degradation abilities of indigenous
      polychlorinated biphenyl (PCB)-degrading bacteria associated with five species of
      mature trees growing naturally in a contaminated site were investigated to
      identify plants that enhance the microbial PCB degradation potential in soil.
      Culturable PCB degraders were associated with every plant species examined in
      both the rhizosphere and root zone, which was defined as the bulk soil in which
      the plant was rooted. Significantly higher numbers of PCB degraders (2.7- to 56.7
      fold-higher means) were detected in the root zones of Austrian pine (Pinus nigra)
      and goat willow (Salix caprea) than in the root zones of other plants or non-root
      containing soil in certain seasons and at certain soil depths. The majority of
      culturable PCB degraders throughout the site and the majority of culturable PCB
      degraders associated with plants were identified as members of the genus
      Rhodococcus by 16S rRNA gene sequence analysis. Other taxa of PCB-degrading
      bacteria included members of the genera Luteibacter and Williamsia, which have
      not previously been shown to include PCB degraders. PCB degradation assays
      revealed that some isolates from the site have broad congener specificities;
      these isolates included one Rhodococcus strain that exhibited degradation
      abilities similar to those of Burkholderia xenovorans LB400. Isolates with broad
      congener specificity were widespread at the site, including in the biostimulated
      root zone of willow. The apparent association of certain plant species with
      increased abundance of indigenous PCB degraders, including organisms with
      outstanding degradation abilities, throughout the root zone supports the notion
      that biostimulation through rhizoremediation is a promising strategy for
      enhancing PCB degradation in situ.

PMID- 16597928
TI  - Distribution of environmental mycobacteria in Karonga District, northern Malawi.
AB  - The genus Mycobacterium includes many species that are commonly found in the
      environment (in soil and water or associated with plants and animals), as well as
      species that are responsible for two major human diseases, tuberculosis
      (Mycobacterium tuberculosis) and leprosy (Mycobacterium leprae). The distribution
      of environmental mycobacteria was investigated in the context of a long-term
      study of leprosy, tuberculosis, Mycobacterium bovis BCG vaccination, and the
      responses of individuals to various mycobacterial antigens in Karonga District,
      northern Malawi, where epidemiological studies had indicated previously that
      people may be exposed to different mycobacterial species in the northern and
      southern parts of the district. A total of 148 soil samples and 24 water samples
      were collected from various locations and examined to determine the presence of
      mycobacteria. The detection method involved semiselective culturing and acid-fast
      staining, following decontamination of samples to enrich mycobacteria and reduce
      the numbers of other microorganisms, or PCR with primers specific for the
      mycobacterial 16S rRNA gene, using DNA extracted directly from soil and water
      samples. Mycobacteria were detected in the majority of the samples, and
      subsequent sequence analysis of PCR products amplified directly from soil DNA
      indicated that most of the products were related to known environmental
      mycobacteria. For both methods the rates of recovery were consistently higher for
      dry season samples than for wet season samples. All isolates cultured from soil
      appeared to be strains of Mycobacterium fortuitum. This study revealed a complex
      pattern for the environmental mycobacterial flora but identified no clear
      differences between the northern and southern parts of Karonga District.

PMID- 16597929
TI  - Deletion of BCY1 from the Saccharomyces cerevisiae genome is semidominant and
      induces autolytic phenotypes suitable for improvement of sparkling wines.
AB  - Autolysis of Saccharomyces cerevisiae is the main source of molecules that
      contribute to the quality of sparkling wines made by the traditional method. In
      this work the possibility of accelerating this slow process in order to improve
      the quality of sparkling wines by using genetically engineered wine yeast strains
      was explored. The effect of partial or total deletion of BCY1 (which encodes a
      regulatory subunit of cAMP-dependent protein kinase A) in haploid and diploid
      (heterozygous and homozygous) yeast strains was studied. We proved that
      heterozygous strains having partial or complete BCY1 deletions have a
      semidominant phenotype for several of the properties studied, including autolysis
      under simulated second-fermentation conditions, in contrast to previously
      published reports describing mutations in BCY1 as recessive. Considering the
      degree of autolysis, ethanol tolerance, and technical feasibility, we propose
      that deletion of the 3' end of the open reading frame of a single copy of BCY1 is
      a way to improve the quality of sparkling wines.

PMID- 16597931
TI  - Evidence for outcrossing via the Buller phenomenon in a substrate simultaneously
      inoculated with spores and mycelium of Agaricus bisporus.
AB  - In Agaricus bisporus, traditional cultivars and most of the wild populations
      belong to A. bisporus var. bisporus, which has a predominantly pseudohomothallic
      life cycle in which most meiospores are heterokaryons (n + n). A lower proportion
      of homokaryotic (n) meiospores, which typify the heterothallic life cycle, also
      are produced. In wild populations, pseudohomothallism was thought previously to
      play a major role, but recent analyses have found that significant outcrossing
      also may occur. We inoculated a standard substrate for A. bisporus cultivation
      simultaneously with homokaryotic mycelium from one parent and spores from a
      second parent. Culture trays produced numerous sporocarps that could
      theoretically have resulted from five different reproductive modes
      (pseudohomothallism, selfing or outcrossing via heterothallism, and selfing or
      outcrossing via the Buller phenomenon [i.e., between a homokaryon and a
      heterokaryon]). Most or all of the sporocarps resulted from outcrossing between
      the inoculated homokaryon and the inoculated heterokaryotic spores (or mycelia
      that grew from them). These data broaden our understanding of population dynamics
      under field conditions and provide an outcrossing method that could be used in
      commercial breeding programs.

PMID- 16597930
TI  - Quantitative real-time PCR analysis of fecal Lactobacillus species in infants
      receiving a prebiotic infant formula.
AB  - The developing intestinal microbiota of breast-fed infants is considered to play
      an important role in the priming of the infants' mucosal and systemic immunity.
      Generally, Bifidobacterium and Lactobacillus predominate the microbiota of breast
      fed infants. In intervention trials it has been shown that lactobacilli can exert
      beneficial effects on, for example, diarrhea and atopy. However, the
      Lactobacillus species distribution in breast-fed or formula-fed infants has not
      yet been determined in great detail. For accurate enumeration of different
      lactobacilli, duplex 5' nuclease assays, targeted on rRNA intergenic spacer
      regions, were developed for Lactobacillus acidophilus, Lactobacillus casei,
      Lactobacillus delbrueckii, Lactobacillus fermentum, Lactobacillus paracasei,
      Lactobacillus plantarum, Lactobacillus reuteri, and Lactobacillus rhamnosus. The
      designed and validated assays were used to determine the amounts of different
      Lactobacillus species in fecal samples of infants receiving a standard formula
      (SF) or a standard formula supplemented with galacto- and fructo-oligosaccharides
      in a 9:1 ratio (OSF). A breast-fed group (BF) was studied in parallel as a
      reference. During the 6-week intervention period a significant increase was shown
      in total percentage of fecal lactobacilli in the BF group (0.8% +/- 0.3% versus
      4.1% +/- 1.5%) and the OSF group (0.8% +/- 0.3% versus 4.4% +/- 1.4%). The
      Lactobacillus species distribution in the OSF group was comparable to breast-fed
      infants, with relatively high levels of L. acidophilus, L. paracasei, and L.
      casei. The SF-fed infants, on the other hand, contained more L. delbrueckii and
      less L. paracasei compared to breast-fed infants and OSF-fed infants. An infant
      milk formula containing a specific mixture of prebiotics is able to induce a
      microbiota that closely resembles the microbiota of BF infants.

PMID- 16597932
TI  - Genotyping and pathogenicity of viral hemorrhagic septicemia virus from free
      living turbot (Psetta maxima) in a Turkish coastal area of the Black Sea.
AB  - Viral hemorrhagic septicemia (VHS) is one of the most serious fish viral diseases
      for cultured rainbow trout (Oncorhynchus mykiss), although VHS virus (VHSV) seems
      to be ubiquitous among marine fishes. In the present study, VHSV isolation was
      performed with free-living and cultured turbot (Psetta maxima) in the Trabzon
      coastal area of the Black Sea to evaluate participation of VHSV in mass
      mortalities of seed-produced turbot larvae. VHSV was detected in 14 of 66 free
      living spawners (positive ratio, 21.2%), 1 of 65 free-living immature fish (1.5%)
      and 7 of 40 cultured brood stock (17.5%), respectively. Based on a partial
      glycoprotein gene nucleotide sequence, Turkish VHSV isolates were classified into
      the class I-e of genotype I and were the most closely related to the GE-1.2
      isolate (>98% identity), which was found >20 years ago in Georgia. Thus, it was
      revealed that Turkish VHSV isolates were not introduced from European countries,
      it could be an indigenous type of VHSV distributing in the Black Sea environment.
      In pathogenicity tests, the Turkish isolates did not induce mortality in turbot
      larvae and rainbow trout fingerlings. Mass mortalities at a rate of approximately
      90% occurred in turbot larvae produced by experimental seeding, although VHSV was
      not detected in any dead fish. Thus, it was concluded that mass mortality in the
      seed-produced turbot larvae was not caused by VHSV infection.

PMID- 16597933
TI  - Introducing TreeClimber, a test to compare microbial community structures.
AB  - The phylogenetic and ecological complexity of microbial communities necessitates
      the development of new methods to determine whether two or more communities have
      the same structure even though it is not possible to sample the communities
      exhaustively. To address this need, we adapted a method used in population
      genetics, the parsimony test, to determine the relatedness of communities. Here
      we describe our implementation of the parsimony test, TreeClimber, in which we
      reanalyzed six previously published studies and compared the results of the
      analysis to those obtained using integral-LIBSHUFF.

PMID- 16597934
TI  - Natural Pseudomonas sp. strain N3 in artificial soil microcosms.
AB  - The lightning-competent Pseudomonas sp. strain N3, recently isolated from soil,
      has been used to study the extent of natural electrotransformation (NET) or
      lightning transformation as a horizontal gene transfer mechanism in soil. The
      variation of electrical fields applied to the soil with a laboratory-scale
      lightning system provides an estimate of the volume of soil affected by NET.
      Based on the range of the electric field that induces NET of Pseudomonas strain
      N3, the volume of soil, where NET could occur, ranges from 2 to 950 m(3) per
      lightning strike. The influence of DNA parameters (amount, size, and purity) and
      DNA soil residence time were also investigated. NET frequencies
      (electrotransformants/recipient cells) ranged from 10(-8) for cell lysate after 1
      day of residence in soil to 4 x 10(-7) with a purified plasmid added immediately
      before the lightning. The electrical field gradient (in kilovolts per cm) also
      played a role as NET frequencies ranging from 1 x 10(-5) at 2.3 kV/cm to 1.7 x
      10(-4) at 6.5 kV/cm.

PMID- 16597935
TI  - Reevaluation of the life cycle of Tuber magnatum.
AB  - Tuber spp. are ectomycorrhizal ascomycetes that produce ascocarps known as
      truffles. Basic aspects of Tuber biology have yet to be fully elucidated. In
      particular, there are conflicting hypotheses concerning the mating system and the
      ploidy level of the mycorrhizal and truffle hyphae. We used polymorphic
      microsatellites to compare the allelic configurations of asci with those from the
      network of the surrounding hyphae in single Tuber magnatum truffles. We then used
      these truffles to inoculate host plants and evaluated the microsatellite
      configurations of the resulting mycorrhizal root tips. These analyses provide
      direct evidence that T. magnatum outcrosses and that its life cycle is
      predominantly haploid. In addition to its scientific significance, this basic
      understanding of the T. magnatum life cycle may have practical importance in
      developing strategies to obtain and select nursery-produced mycorrhizal plants as
      well as in the management of artificial plantations of this and other Tuber spp.

PMID- 16597936
TI  - A mono-2-ethylhexyl phthalate hydrolase from a Gordonia sp. that is able to
      dissimilate di-2-ethylhexyl phthalate.
AB  - Gordonia sp. strain P8219, a strain able to decompose di-2-ethylhexyl phthalate,
      was isolated from machine oil-contaminated soil. Mono-2-ethylhexyl phthalate
      hydrolase was purified from cell extracts of this strain. This enzyme was a
      32,164-Da homodimeric protein, and it effectively hydrolyzed monophthalate
      esters, such as monoethyl, monobutyl, monohexyl, and mono-2-ethylhexyl phthalate.
      The K(m) and V(max) values for mono-2-ethylhexyl phthalate were 26.9 +/- 4.3
      microM and 18.1 +/- 0.9 micromol/min . mg protein, respectively. The deduced
      amino acid sequence of the enzyme exhibited less than 30% homology with those of
      meta-cleavage hydrolases which are serine hydrolases but exhibited no significant
      homology with the sequences of serine esterases. The pentapeptide motif GXSXG,
      which is conserved in serine hydrolases, was present in the sequence. The
      enzymatic properties and features of the primary structure suggested that this
      enzyme is a novel enzyme belonging to an independent group of serine hydrolases.

PMID- 16597937
TI  - Fatty acid-oxidizing consortia along a nutrient gradient in the Florida
      Everglades.
AB  - The Florida Everglades is one of the largest freshwater marshes in North America
      and has been subject to eutrophication for decades. A gradient in P
      concentrations extends for several kilometers into the interior of the northern
      regions of the marsh, and the structure and function of soil microbial
      communities vary along the gradient. In this study, stable isotope probing was
      employed to investigate the fate of carbon from the fermentation products
      propionate and butyrate in soils from three sites along the nutrient gradient.
      For propionate microcosms, 16S rRNA gene clone libraries from eutrophic and
      transition sites were dominated by sequences related to previously described
      propionate oxidizers, such as Pelotomaculum spp. and Syntrophobacter spp.
      Significant representation was also observed for sequences related to Smithella
      propionica, which dismutates propionate to butyrate. Sequences of dominant
      phylotypes from oligotrophic samples did not cluster with known syntrophs but
      with sulfate-reducing prokaryotes (SRP) and Pelobacter spp. In butyrate
      microcosms, sequences clustering with Syntrophospora spp. and Syntrophomonas spp.
      dominated eutrophic microcosms, and sequences related to Pelospora dominated the
      transition microcosm. Sequences related to Pelospora spp. and SRP dominated clone
      libraries from oligotrophic microcosms. Sequences from diverse bacterial phyla
      and primary fermenters were also present in most libraries. Archaeal sequences
      from eutrophic microcosms included sequences characteristic of
      Methanomicrobiaceae, Methanospirillaceae, and Methanosaetaceae. Oligotrophic
      microcosms were dominated by acetotrophs, including sequences related to
      Methanosarcina, suggesting accumulation of acetate.

PMID- 16597938
TI  - Novel hydrophobic surface binding protein, HsbA, produced by Aspergillus oryzae.
AB  - Hydrophobic surface binding protein A (HsbA) is a secreted protein (14.5 kDa)
      isolated from the culture broth of Aspergillus oryzae RIB40 grown in a medium
      containing polybutylene succinate-co-adipate (PBSA) as a sole carbon source. We
      purified HsbA from the culture broth and determined its N-terminal amino acid
      sequence. We found a DNA sequence encoding a protein whose N terminus matched
      that of purified HsbA in the A. ozyzae genomic sequence. We cloned the hsbA
      genomic DNA and cDNA from A. oryzae and constructed a recombinant A. oryzae
      strain highly expressing hsbA. Orthologues of HsbA were present in animal
      pathogenic and entomopathogenic fungi. Heterologously synthesized HsbA was
      purified and biochemically characterized. Although the HsbA amino acid sequence
      suggests that HsbA may be hydrophilic, HsbA adsorbed to hydrophobic PBSA surfaces
      in the presence of NaCl or CaCl(2). When HsbA was adsorbed on the hydrophobic
      PBSA surfaces, it promoted PBSA degradation via the CutL1 polyesterase. CutL1
      interacts directly with HsbA attached to the hydrophobic QCM electrode surface.
      These results suggest that when HsbA is adsorbed onto the PBSA surface, it
      recruits CutL1, and that when CutL1 is accumulated on the PBSA surface, it
      stimulates PBSA degradation. We previously reported that when the A. oryzae
      hydrophobin RolA is bound to PBSA surfaces, it too specifically recruits CutL1.
      Since HsbA is not a hydrophobin, A. oryzae may use several types of proteins to
      recruit lytic enzymes to the surface of hydrophobic solid materials and promote
      their degradation.

PMID- 16597939
TI  - Occurrence of six honeybee viruses in diseased Austrian apiaries.
AB  - The occurrence, prevalence, and distribution patterns of acute bee paralysis
      virus (ABPV), black queen cell virus (BQCV), chronic bee paralysis virus (CBPV),
      deformed wing virus (DWV), Kashmir bee virus (KBV), and sacbrood virus (SBV) were
      investigated in 90 Austrian honeybee colonies suffering from symptoms of
      depopulation, sudden collapse, paralysis, or dark coloring by employing reverse
      transcription-PCR. Infestation with parasites was also recorded. The samples
      originated from all parts of Austria. The most prevalent virus was DWV, present
      in 91% of samples, followed by ABPV, SBV, and BQCV (68%, 49%, and 30%,
      respectively). CBPV was detected in 10% of colonies, while KBV was not present in
      any sample. In most samples, more than one virus was identified. The distribution
      pattern of ABPV, BQCV, CBPV, and SBV varied considerably in the different
      geographic regions investigated, while DWV was widespread in all Austrian federal
      states. In bees that showed dark coloring and disorientation, CBPV was always
      detected. Simultaneous infections of DWV and ABPV were most frequently observed
      in colonies suffering from weakness, depopulation, and sudden collapse. Bees
      obtained from apparently healthy colonies within the same apiaries showed a
      similar distribution pattern of viruses; however, the relative virus load was 10
      to 126 times lower than in bees from diseased colonies. A limited number of bee
      samples from surrounding central European countries (Germany, Poland, Hungary,
      and Slovenia) were also tested for the presence of the above viruses. Variances
      were found in the distribution of BQCV and SBV.

PMID- 16597940
TI  - Assessment of the environmental fate of the biological control agent of fire
      blight, Pseudomonas fluorescens EPS62e, on apple by culture and real-time PCR
      methods.
AB  - The colonization of apple blossoms and leaves by Pseudomonas fluorescens EPS62e
      was monitored in greenhouse and field trials using cultivable cell counting and
      real-time PCR. The real-time PCR provided a specific quantitative method for the
      detection of strain EPS62e. The detection level was around 10(2) cells g (fresh
      weight)(-1) and the standard curve was linear within a 5-log range. EPS62e
      actively colonized flowers reaching values from 10(7) to 10(8) cells per blossom.
      In apple flowers, no significant differences were observed between population
      levels obtained by real-time PCR and plating, suggesting that viable but
      nonculturable (VBNC) cells and residual nondegraded DNA were not present. In
      contrast, on apple leaves, where cultivable populations of EPS62e decreased with
      time, significant differences were observed between real-time PCR and plating.
      These differences indicate the presence of VBNC cells or nondegraded DNA after
      cell death. Therefore, the EPS62e population was under optimal conditions during
      the colonization of flowers but it was stressed and poorly survived on leaves. It
      was concluded that for monitoring this biological control agent, the combined use
      of cultivable cell count and real-time PCR is necessary.

PMID- 16597941
TI  - Biodiversity of amoebae and amoeba-resisting bacteria in a hospital water
      network.
AB  - Free-living amoebae (FLA) are ubiquitous organisms that have been isolated from
      various domestic water systems, such as cooling towers and hospital water
      networks. In addition to their own pathogenicity, FLA can also act as Trojan
      horses and be naturally infected with amoeba-resisting bacteria (ARB) that may be
      involved in human infections, such as pneumonia. We investigated the biodiversity
      of bacteria and their amoebal hosts in a hospital water network. Using amoebal
      enrichment on nonnutrient agar, we isolated 15 protist strains from 200 (7.5%)
      samples. One thermotolerant Hartmannella vermiformis isolate harbored both
      Legionella pneumophila and Bradyrhizobium japonicum. By using amoebal coculture
      with axenic Acanthamoeba castellanii as the cellular background, we recovered at
      least one ARB from 45.5% of the samples. Four new ARB isolates were recovered by
      culture, and one of these isolates was widely present in the water network.
      Alphaproteobacteria (such as Rhodoplanes, Methylobacterium, Bradyrhizobium,
      Afipia, and Bosea) were recovered from 30.5% of the samples, mycobacteria
      (Mycobacterium gordonae, Mycobacterium kansasii, and Mycobacterium xenopi) were
      recovered from 20.5% of the samples, and Gammaproteobacteria (Legionella) were
      recovered from 5.5% of the samples. No Chlamydia or Chlamydia-like organisms were
      recovered by amoebal coculture or detected by PCR. The observed strong
      association between the presence of amoebae and the presence of Legionella (P <
      0.001) and mycobacteria (P = 0.009) further suggests that FLA are a reservoir for
      these ARB and underlines the importance of considering amoebae when water control
      measures are designed.

PMID- 16597942
TI  - Discovery of natural atypical nonhemolytic Listeria seeligeri isolates.
AB  - We found seven Listeria isolates, initially identified as isolates with the
      Xyl(+) Rha(-) biotype of Listeria welshimeri by phenotypic tests, which exhibited
      discrepant genotypic properties in a well-validated Listeria species
      identification oligonucleotide microarray. The microarray gives results of these
      seven isolates being atypical hly-negative L. seeligeri isolates, not L.
      welshimeri isolates. The aberrant L. seeligeri isolates were d-xylose
      fermentation positive, l-rhamnose fermentation negative (Xyl(+) Rha(-)), and
      nonhemolytic on blood agar and in the CAMP test with both Staphylococcus aureus
      (S(-) reaction) and Rhodococcus equi (R(-) reaction). All genes of the prfA
      cluster of L. seeligeri, located in the prs-ldh region, including the orfA2,
      orfD, prfA, orfE, plcA, hly, orfK, mpl, actA, dplcB, plcB, orfH, orfX, orfI,
      orfP, orfB, and orfA genes, were checked by PCR and direct sequencing for
      evidence of their presence in the atypical isolates. The prs-prfA cluster-ldh
      region of the L. seeligeri isolates was approximately threefold shorter due to
      the loss of orfD, prfA, orfE, plcA, hly, orfK, mpl, actA, dplcB, plcB, orfH,
      orfX, and orfI. The genetic map order of the cluster genes of all the atypical L.
      seeligeri isolates was prs-orfA2-orfP-orfB-orfA-ldh, which was comparable to the
      similar region in L. welshimeri, with the exception of the presence of orfA2. DNA
      sequencing and phylogenetic analysis of 17 housekeeping genes indicated an L.
      seeligeri genomic background in all seven of the atypical hly-negative L.
      seeligeri isolates. Thus, the novel biotype of Xyl(+) Rha(-) Hly(-) L. seeligeri
      strains can only be distinguished from Xyl(+) Rha(-) L. welshimeri strains
      genotypically, not phenotypically. In contrast, the Rha(+) Xyl(+) biotype of L.
      welshimeri would not present an identification issue.

PMID- 16597943
TI  - YliH (BssR) and YceP (BssS) regulate Escherichia coli K-12 biofilm formation by
      influencing cell signaling.
AB  - We previously discovered that yliH and yceP are induced in Escherichia coli
      biofilms (D. Ren, L. A. Bedzyk, S. M. Thomas, R. W. Ye, and T. K. Wood, Appl.
      Microbiol. Biotechnol. 64:515-524, 2004). Here, it is shown that deletion of yceP
      (b1060) and yliH (b0836) increases biofilm formation in continuous-flow chambers
      with minimal glucose medium by increasing biofilm mass (240- to 290-fold),
      surface coverage (16- to 31-fold), and mean thickness (2,800-fold). To determine
      the genetic basis of the increase in biofilm formation, we examined the
      differential gene expression profile in biofilms for both the mutants relative to
      the wild-type strain in rich medium with glucose and found that 372 to 882 genes
      were induced and that 76 to 337 were repressed consistently >2-fold (P < or =
      0.05). The increase in biofilm formation was related to differential expression
      of genes related to stress response (8 to 64 genes) for both mutants, including
      rpoS and sdiA. More importantly, 42 to 130 genes related to autoinducer 2 cell
      signaling were also differentially expressed, including gadAB and flgBCEGHIJLMN,
      as well as signaling through indole, since 17 to 26 indole-related genes were
      differentially expressed, including phoAER, gltBD, mtr (encodes protein for
      indole import), and acrEF (encodes proteins for indole export). Increased biofilm
      formation in the yliH and yceP mutants in LB supplemented with 0.2% glucose (LB
      glu) occurred through a reduction in extracellular and intracellular indole
      concentrations in both mutants (50- to 140-fold), and the addition of indole to
      the culture restored the wild-type biofilm phenotype; hence, indole represses
      biofilms. Additionally, both mutants regulate biofilms through quorum sensing,
      since deletion of either yliH or yceP increased extracellular autoinducer 2
      concentrations 50-fold when grown in complex medium (most notably in the
      stationary phase). Both proteins are involved in motility regulation, since YliH
      (127 amino acids) and YceP (84 amino acids) repressed motility two to sevenfold
      (P < or = 0.05) in LB, and YceP repressed motility sevenfold (P < or = 0.05) in
      LB glu. Heightened motility in the yceP mutant occurred, due to increased
      transcription of the flagella and motility loci, including fliC, motA, and qseB
      (3- to 86-fold). We propose new names for these two loci: bssR for yliH and bssS
      for yceP, based on the phrase "regulator of biofilm through signal secretion."

PMID- 16597945
TI  - Male-specific coliphages as indicators of thermal inactivation of pathogens in
      biosolids.
AB  - Male-specific (F+) coliphages have been proposed as a candidate indicator of
      fecal contamination and of virus reduction in waste treatment. However, in this
      and earlier work with a laboratory thermophilic anaerobic digester, a heat
      resistant fraction of F+ coliphage populations indigenous to municipal wastewater
      and sludge was evident. We therefore isolated coliphages from municipal
      wastewater sludge and from biosolid samples after thermophilic anaerobic
      digestion to evaluate the susceptibility of specific groups to thermal
      inactivation. Similar numbers of F+ DNA and F+ RNA coliphages were found in
      untreated sludge, but the majority of isolates in digested biosolids were group I
      F+ RNA phages. Separate experiments on individual isolates at 53 degrees C
      confirmed the apparent heat resistance of group I F+ RNA coliphages as well as
      the susceptibility of group III F+ RNA coliphages. Although few F+ DNA coliphages
      were recovered from the treated biosolid samples, thermal inactivation
      experiments indicated heat resistance similar to that of group I F+ RNA phages.
      Hence, F+ DNA coliphage reductions during thermophilic anaerobic digestion are
      probably related to mechanisms other than thermal inactivation. Further studies
      should focus on the group III F+ RNA coliphages as potential indicators of
      reductions of heat-resistant pathogens in thermal processes for sludge treatment.

PMID- 16597944
TI  - Development and characterization of stable sediment-free anaerobic bacterial
      enrichment cultures that dechlorinate aroclor 1260.
AB  - We have developed sediment-free anaerobic enrichment cultures that dechlorinate a
      broad spectrum of highly chlorinated polychlorinated biphenyls (PCBs). The
      cultures were developed from Aroclor 1260-contaminated sediment from the
      Housatonic River in Lenox, MA. Sediment slurries were primed with 2,6
      dibromobiphenyl to stimulate Process N dechlorination (primarily meta
      dechlorination), and sediment was gradually removed by successive transfers (10%)
      to minimal medium. The cultures grow on pyruvate, butyrate, or acetate plus H(2).
      Gas chromatography-electron capture detector analysis demonstrated that the
      cultures extensively dechlorinate 50 to 500 mug/ml of Aroclor 1260 at 22 to 24
      degrees C by Dechlorination Process N. Triplicate cultures of the eighth transfer
      without sediment dechlorinated 76% of the hexa- through nonachlorobiphenyls in
      Aroclor 1260 (250 mug/ml) to tri- through pentachlorobiphenyls in 110 days. At
      least 64 PCB congeners, all of which are chlorinated on both rings and 47 of
      which have six or more chlorines, were substrates for this dechlorination. To
      characterize the bacterial diversity in the enrichments, we used eubacterial
      primers to amplify and clone 16S rRNA genes from DNA extracted from cultures
      grown on acetate plus H(2). Restriction fragment length polymorphism analysis of
      107 clones demonstrated the presence of Thauera-like Betaproteobacteria,
      Geobacter-like Deltaproteobacteria, Pseudomonas species, various Clostridiales,
      Bacteroidetes, Dehalococcoides of the Chloroflexi group, and unclassified
      Eubacteria. Our development of highly enriched, robust, stable, sediment-free
      cultures that extensively dechlorinate a highly chlorinated commercial PCB
      mixture is a major and unprecedented breakthrough in the field. It will enable
      intensive study of the organisms and genes responsible for a major PCB
      dechlorination process that occurs in the environment and could also lead to
      effective remediation applications.

PMID- 16597946
TI  - Degradation of aroclor 1242 dechlorination products in sediments by Burkholderia
      xenovorans LB400(ohb) and Rhodococcus sp. strain RHA1(fcb).
AB  - Burkholderia xenovorans strain LB400, which possesses the biphenyl pathway, was
      engineered to contain the oxygenolytic ortho dehalogenation (ohb) operon,
      allowing it to grow on 2-chlorobenzoate and to completely mineralize 2
      chlorobiphenyl. A two-stage anaerobic/aerobic biotreatment process for Aroclor
      1242-contaminated sediment was simulated, and the degradation activities and
      genetic stabilities of LB400(ohb) and the previously constructed strain
      RHA1(fcb), capable of growth on 4-chlorobenzoate, were monitored during the
      aerobic phase. The population dynamics of both strains were also followed by
      selective plating and real-time PCR, with comparable results; populations of both
      recombinants increased in the contaminated sediment. Inoculation at different
      cell densities (10(4) or 10(6) cells g(-1) sediment) did not affect the extent of
      polychlorinated biphenyl (PCB) biodegradation. After 30 days, PCB removal rates
      for high and low inoculation densities were 57% and 54%, respectively, during the
      aerobic phase.

PMID- 16597947
TI  - Paenibacillus curdlanolyticus strain B-6 xylanolytic-cellulolytic enzyme system
      that degrades insoluble polysaccharides.
AB  - A facultatively anaerobic bacterium, Paenibacillus curdlanolyticus B-6, isolated
      from an anaerobic digester produces an extracellular xylanolytic-cellulolytic
      enzyme system containing xylanase, beta-xylosidase, arabinofuranosidase, acetyl
      esterase, mannanase, carboxymethyl cellulase (CMCase), avicelase,
      cellobiohydrolase, beta-glucosidase, amylase, and chitinase when grown on xylan
      under aerobic conditions. During growth on xylan, the bacterial cells were found
      to adhere to xylan from the early exponential growth phase to the late stationary
      growth phase. Scanning electron microscopic analysis revealed the adhesion of
      cells to xylan. The crude enzyme preparation was found to be capable of binding
      to insoluble xylan and Avicel. The xylanolytic-cellulolytic enzyme system
      efficiently hydrolyzed insoluble xylan, Avicel, and corn hulls to soluble sugars
      that were exclusively xylose and glucose. Sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) of a crude enzyme preparation exhibited at least
      17 proteins, and zymograms revealed multiple xylanases and cellulases containing
      12 xylanases and 9 CMCases. The cellulose-binding proteins, which are mainly in a
      multienzyme complex, were isolated from the crude enzyme preparation by affinity
      purification on cellulose. This showed nine proteins by SDS-PAGE and eight
      xylanases and six CMCases on zymograms. Sephacryl S-300 gel filtration showed
      that the cellulose-binding proteins consisted of two multienzyme complexes with
      molecular masses of 1,450 and 400 kDa. The results indicated that the xylanolytic
      cellulolytic enzyme system of this bacterium exists as multienzyme complexes.

PMID- 16597948
TI  - Purification and characterization of TrzF: biuret hydrolysis by allophanate
      hydrolase supports growth.
AB  - TrzF, the allophanate hydrolase from Enterobacter cloacae strain 99, was cloned,
      overexpressed in the presence of a chaperone protein, and purified to
      homogeneity. Native TrzF had a subunit molecular weight of 65,401 and a subunit
      stoichiometry of alpha(2) and did not contain significant levels of metals. TrzF
      showed time-dependent inhibition by phenyl phosphorodiamidate and is a member of
      the amidase signature protein family. TrzF was highly active in the hydrolysis of
      allophanate but was not active with urea, despite having been previously
      considered a urea amidolyase. TrzF showed lower activity with malonamate,
      malonamide, and biuret. The allophanate hydrolase from Pseudomonas sp. strain
      ADP, AtzF, was also shown to hydrolyze biuret slowly. Since biuret and
      allophanate are consecutive metabolites in cyanuric acid metabolism, the low
      level of biuret hydrolase activity can have physiological significance. A
      recombinant Escherichia coli strain containing atzD, encoding cyanuric acid
      hydrolase that produces biuret, and atzF grew slowly on cyanuric acid as a source
      of nitrogen. The amount of growth produced was consistent with the liberation of
      3 mol of ammonia from cyanuric acid. In vitro, TrzF was shown to hydrolyze biuret
      to liberate 3 mol of ammonia. The biuret hydrolyzing activity of TrzF might also
      be physiologically relevant in native strains. E. cloacae strain 99 grows on
      cyanuric acid with a significant accumulation of biuret.

PMID- 16597949
TI  - Abundance and distribution of Ostreococcus sp. in the San Pedro Channel,
      California, as revealed by quantitative PCR.
AB  - Ostreococcus is a genus of widely distributed marine phytoplankton which are
      picoplanktonic in size (<2 mum) and capable of rapid growth. Although
      Ostreococcus has been detected around the world, little quantitative information
      exists on its contribution to planktonic communities. We designed and implemented
      a genus-specific TaqMan-based quantitative PCR (qPCR) assay to investigate the
      dynamics and ecology of Ostreococcus at the USC Microbial Observatory (eastern
      North Pacific). Samples were collected from 5 m and the deep chlorophyll maximum
      (DCM) between September 2000 and August 2002. Ostreococcus abundance at 5 m was
      generally <5.0 x 10(3) cells ml(-1), with a maximum of 8.2 x 10(4) cells ml(-1).
      Ostreococcus abundance was typically higher at the DCM, with a maximum of 3.2 x
      10(5) cells ml(-1). The vertical distribution of Ostreococcus was examined in
      March 2005 and compared to the distribution of phototrophic picoeukaryotes (PPE)
      measured by flow cytometry. The largest contribution to PPE abundance by
      Ostreococcus was approximately 70% and occurred at 30 m, near the DCM. Despite
      its relatively low abundance, the depth-integrated standing stock of Ostreococcus
      in March 2005 was approximately 30 mg C m(-2). Our work provides a new technique
      for quantifying the abundance of Ostreococcus and demonstrates the seasonal
      dynamics of this genus and its contribution to picoeukaryote biomass at our
      coastal sampling station.

PMID- 16597950
TI  - Emergence of distinct genotypes of Cryptosporidium parvum in structured host
      populations.
AB  - Cryptosporidium parvum is an apicomplexan parasite that infects humans and
      ruminants. C. parvum isolated from cattle in northeastern Turkey and in Israel
      was genotyped using multiple polymorphic genetic markers, and the two populations
      were compared to assess the effect of cattle husbandry on the parasite's
      population structure. Dairy herds in Israel are permanently confined with
      essentially no opportunity for direct herd-to-herd transmission, whereas in
      Turkey there are more opportunities for transmission as animals range over wider
      areas and are frequently traded. A total of 76 C. parvum isolates from 16
      locations in Israel and seven farms in the Kars region in northeastern Turkey
      were genotyped using 16 mini- and microsatellite markers. Significantly, in both
      countries distinct multilocus genotypes confined to individual farms were
      detected. The number of genotypes per farm was higher and mixed isolates were
      more frequent in Turkey than in Israel. As expected from the presence of distinct
      multilocus genotypes in individual herds, linkage disequilibrium among loci was
      detected in Israel. Together, these observations show that genetically distinct
      populations of C. parvum can emerge within a group of hosts in a relatively short
      time. This may explain the frequent detection of host-specific genotypes with
      unknown taxonomic status in surface water and the existence of geographically
      restricted C. hominis genotypes in humans.

PMID- 16597952
TI  - An efficient method of selectable marker gene excision by Xer recombination for
      gene replacement in bacterial chromosomes.
AB  - A simple, effective method of unlabeled, stable gene insertion into bacterial
      chromosomes has been developed. This utilizes an insertion cassette consisting of
      an antibiotic resistance gene flanked by dif sites and regions homologous to the
      chromosomal target locus. dif is the recognition sequence for the native Xer site
      specific recombinases responsible for chromosome and plasmid dimer resolution:
      XerC/XerD in Escherichia coli and RipX/CodV in Bacillus subtilis. Following
      integration of the insertion cassette into the chromosomal target locus by
      homologous recombination, these recombinases act to resolve the two directly
      repeated dif sites to a single site, thus excising the antibiotic resistance
      gene. Previous approaches have required the inclusion of exogenous site-specific
      recombinases or transposases in trans; our strategy demonstrates that this is
      unnecessary, since an effective recombination system is already present in
      bacteria. The high recombination frequency makes the inclusion of a counter
      selectable marker gene unnecessary.

PMID- 16597951
TI  - Characterization of the P450 monooxygenase NysL, responsible for C-10
      hydroxylation during biosynthesis of the polyene macrolide antibiotic nystatin in
      Streptomyces noursei.
AB  - The nysL gene, encoding a putative P450 monooxygenase, was identified in the
      nystatin biosynthetic gene cluster of Streptomyces noursei. Although it has been
      proposed that NysL is responsible for hydroxylation of the nystatin precursor,
      experimental evidence for this activity was lacking. The nysL gene was
      inactivated in S. noursei by gene replacement, and the resulting mutant was shown
      to produce 10-deoxynystatin. Purification and an in vitro activity assay for 10
      deoxynystatin demonstrated its antifungal activity being equal to that of
      nystatin. The NysL protein was expressed heterologously in Escherichia coli as a
      His-tagged protein and used in an enzyme assay with 10-deoxynystatin as a
      substrate. The results obtained clearly demonstrated that NysL is a hydroxylase
      responsible for the post-polyketide synthase modification of 10-deoxynystatin at
      position C-10. Kinetic studies with the purified recombinant enzyme allowed
      determination of K(m) and k(cat) and revealed no inhibition of recombinant NysL
      by either the substrate or the product. These studies open the possibility for in
      vitro evolution of NysL aimed at changing its specificity, thereby providing new
      opportunities for engineered biosynthesis of novel nystatin analogues
      hydroxylated at alternative positions of the macrolactone ring.

PMID- 16597953
TI  - Symbiotic Bradyrhizobium japonicum reduces N2O surrounding the soybean root
      system via nitrous oxide reductase.
AB  - N(2)O reductase activity in soybean nodules formed with Bradyrhizobium japonicum
      was evaluated from N(2)O uptake and conversion of (15)N-N(2)O into (15)N-N(2).
      Free-living cells of USDA110 showed N(2)O reductase activity, whereas a nosZ
      mutant did not. Complementation of the nosZ mutant with two cosmids containing
      the nosRZDFYLX genes of B. japonicum USDA110 restored the N(2)O reductase
      activity. When detached soybean nodules formed with USDA110 were fed with (15)N
      N(2)O, they rapidly emitted (15)N-N(2) outside the nodules at a ratio of 98.5% of
      (15)N-N(2)O uptake, but nodules inoculated with the nosZ mutant did not.
      Surprisingly, N(2)O uptake by soybean roots nodulated with USDA110 was observed
      even in ambient air containing a low concentration of N(2)O (0.34 ppm). These
      results indicate that the conversion of N(2)O to N(2) depends exclusively on the
      respiratory N(2)O reductase and that soybean roots nodulated with B. japonicum
      carrying the nos genes are able to remove very low concentrations of N(2)O.

PMID- 16597954
TI  - Indirect measurement of the lag time distribution of single cells of Listeria
      innocua in food.
AB  - The distribution of log counts at a given time during the exponential growth
      phase of Listeria innocua measured in food samples inoculated with one cell each
      was applied to estimate the distribution of the single-cell lag times. Three
      replicate experiments in broth showed that the distribution of the log counts is
      a linear mapping of the distribution of the detection times measured by optical
      density. The detection time distribution reflects the lag time distribution but
      is shifted in time. The log count distribution was applied to estimate the
      distributions of the lag times in a liquid dairy product and in liver pate after
      different heat treatments. Two batches of ca. 100 samples of the dairy product
      were inoculated and heated at 55 degrees C for 45 min or at 62 degrees C for 2
      min, and an unheated batch was incubated at 4 degrees C. The final concentration
      of surviving bacteria was ca. 1 cell per sample. The unheated cells showed the
      shortest lag times with the smallest variance. The mean and the variance of the
      lag times of the surviving cells at 62 degrees C were greater than those of the
      cells treated at 55 degrees C. Three batches of pate samples were heated at 55
      degrees C for 25 min, 62 degrees C for 81 s, or 65 degrees C for 20 s. A control
      batch was inoculated but not heated. All pate samples were incubated at 15
      degrees C. The distribution of the lag times of the cells heated at 55 degrees C
      was not significantly different from that of the unheated cells. However, at the
      higher temperatures, 62 degrees C and 65 degrees C, the lag duration was longer
      and its variance greater.

PMID- 16597955
TI  - Cloning and sequencing of the ompA gene of Enterobacter sakazakii and development
      of an ompA-targeted PCR for rapid detection of Enterobacter sakazakii in infant
      formula.
AB  - Enterobacter sakazakii is an emerging, infant formula-borne pathogen that causes
      severe meningitis, meningoencephalitis, sepsis, and necrotizing enterocolitis in
      neonates and infants, with a high fatality rate. Traditional detection methods
      take up to 7 days to identify E. sakazakii. The outer membrane protein A gene
      (ompA), along with its flanking sequences from E. sakazakii (ATCC 51329), was
      cloned in the pGEM-T Easy vector and sequenced. Comparison of the nucleotide and
      deduced amino acid sequences of the ompA gene with other sequences available in
      the GenBank database revealed a high degree of homology with ompA genes of other
      gram-negative bacteria belonging to the Enterobacteriaceae. Based on regions of
      the ompA gene unique to E. sakazakii, two primers were synthesized to develop and
      optimize an E. sakazakii-specific PCR. The PCR amplified a 469-bp DNA product
      from all E. sakazakii strains tested but not from other bacteria. Experiments to
      determine the sensitivity of the PCR indicated that it could detect as few as
      10(3) CFU/ml of E. sakazakii bacteria in infant formula directly and 10(-1)
      CFU/ml after an 8-h enrichment step. We conclude that this PCR, combined with
      enrichment culturing, has the potential to be used as a rapid tool for detecting
      the presence of E. sakazakii in infant formula.

PMID- 16597956
TI  - Identification of essential operons with a rhamnose-inducible promoter in
      Burkholderia cenocepacia.
AB  - Scanning of bacterial genomes to identify essential genes is of biological
      interest, for understanding the basic functions required for life, and of
      practical interest, for the identification of novel targets for new antimicrobial
      therapies. In particular, the lack of efficacious antimicrobial treatments for
      infections caused by the Burkholderia cepacia complex is causing high morbidity
      and mortality of cystic fibrosis patients and of patients with nosocomial
      infections. Here, we present a method based on delivery of the tightly regulated
      rhamnose-inducible promoter P(rhaB) for identifying essential genes and operons
      in Burkholderia cenocepacia. We demonstrate that different levels of gene
      expression can be achieved by using two vectors that deliver P(rhaB) at two
      different distances from the site of insertion. One of these vectors places
      P(rhaB) at the site of transposon insertion, while the other incorporates the
      enhanced green fluorescent protein gene (e-gfp) downstream from P(rhaB). This
      system allows us to identify essential genes and operons in B. cenocepacia and
      provides a new tool for systematically identifying and functionally
      characterizing essential genes at the genomic level.

PMID- 16597957
TI  - Bioenergetic mechanism for nisin resistance, induced by the acid tolerance
      response of Listeria monocytogenes.
AB  - This study examined the bioenergetics of Listeria monocytogenes, induced to an
      acid tolerance response (ATR). Changes in bioenergetic parameters were consistent
      with the increased resistance of ATR-induced (ATR(+)) cells to the antimicrobial
      peptide nisin. These changes may also explain the increased resistance of L.
      monocytogenes to other lethal factors. ATR(+) cells had lower transmembrane pH
      (DeltapH) and electric potential (Deltapsi) than the control (ATR(-)) cells. The
      decreased proton motive force (PMF) of ATR(+) cells increased their resistance to
      nisin, the action of which is enhanced by energized membranes. Paradoxically, the
      intracellular ATP levels of the PMF-depleted ATR(+) cells were approximately 7
      fold higher than those in ATR(-) cells. This suggested a role for the F(o)F(1)
      ATPase enzyme complex, which converts the energy of ATP hydrolysis to PMF.
      Inhibition of the F(o)F(1) ATPase enzyme complex by N'-N'-1,3
      dicyclohexylcarbodiimide increased ATP levels in ATR(-) but not in ATR(+) cells,
      where ATPase activity was already low. Spectrometric analyses (surface-enhanced
      laser desorption ionization-time of flight mass spectrometry) suggested that in
      ATR(+) listeriae, the downregulation of the proton-translocating c subunit of the
      F(o)F(1) ATPase was responsible for the decreased ATPase activity, thereby
      sparing vital ATP. These data suggest that regulation of F(o)F(1) ATPase plays an
      important role in the acid tolerance response of L. monocytogenes and in its
      induced resistance to nisin.

PMID- 16597958
TI  - Analyses of the red-dry-rough phenotype of an Escherichia coli O157:H7 strain and
      its role in biofilm formation and resistance to antibacterial agents.
AB  - In a previous study, we identified Congo red-binding and -nonbinding phase
      variants of Escherichia coli serotype O157:H7 strain ATCC 43895. The Congo red
      binding variant, strain 43895OR, produced a dry, aggregative colony that was
      similar to the red, dry, and rough (rdar) phenotype characteristic of certain
      strains of Salmonella. In contrast, variant 43895OW produced a smooth and white
      colony morphology. In this study, we show that, similar to rdar strains of
      Salmonella enterica serovar Typhimurium, strain 43895OR forms large aggregates in
      broth cultures, firm pellicles at the air-medium interface on glass, and dense
      biofilms on glass and polystyrene. However, unlike S. enterica serovar
      Typhimurium, strain 43895OR does not stain positive for cellulose production.
      When strain 43895OR was fixed on agar, scanning electron microscopy showed cells
      expressing extracellular matrix (ECM) containing curli fibers. Strain 43895OW was
      devoid of any ECM or curli fibers on agar but showed expression of curli fibers
      during attachment to glass. Strain 43895OR produced >4-fold-larger amounts of
      biofilm than strain 43895OW on polystyrene, glass, stainless steel, and Teflon;
      formation was >3-fold higher in rich medium than in nutrient-limited medium.
      Biofilm-associated cells of both strains showed statistically greater resistance
      (P < 0.05) to hydrogen peroxide and quaternary ammonium sanitizer than their
      respective planktonic cells. This study shows that the rdar phenotype of E. coli
      O157:H7 strain 43895OR is important in multicellular growth, biofilm formation,
      and resistance to sanitizers. However, the lack of cellulose production by strain
      43895OR indicates important differences in the ECM composition compared to that
      of Salmonella.

PMID- 16597960
TI  - Overexpression of the 14alpha-demethylase target gene (CYP51) mediates fungicide
      resistance in Blumeriella jaapii.
AB  - Sterol demethylation inhibitor (DMI) fungicides are widely used to control fungi
      pathogenic to humans and plants. Resistance to DMIs is mediated either through
      alterations in the structure of the target enzyme CYP51 (encoding 14alpha
      demethylase), through increased expression of the CYP51 gene, or through
      increased expression of efflux pumps. We found that CYP51 expression in DMI
      resistant (DMI(R)) isolates of the cherry leaf spot pathogen Blumeriella jaapii
      was increased 5- to 12-fold compared to that in DMI-sensitive (DMI(S)) isolates.
      Analysis of sequences upstream of CYP51 in 59 DMI(R) isolates revealed that
      various forms of a truncated non-long terminal direct repeat long interspersed
      nuclear element retrotransposon were present in all instances. Similar inserts
      upstream of CYP51 were not present in any of 22 DMI(S) isolates examined.

PMID- 16597959
TI  - Engineered biosynthesis of a novel amidated polyketide, using the malonamyl
      specific initiation module from the oxytetracycline polyketide synthase.
AB  - Tetracyclines are aromatic polyketides biosynthesized by bacterial type II
      polyketide synthases (PKSs). Understanding the biochemistry of tetracycline PKSs
      is an important step toward the rational and combinatorial manipulation of
      tetracycline biosynthesis. To this end, we have sequenced the gene cluster of
      oxytetracycline (oxy and otc genes) PKS genes from Streptomyces rimosus. Sequence
      analysis revealed a total of 21 genes between the otrA and otrB resistance genes.
      We hypothesized that an amidotransferase, OxyD, synthesizes the malonamate
      starter unit that is a universal building block for tetracycline compounds. In
      vivo reconstitution using strain CH999 revealed that the minimal PKS and OxyD are
      necessary and sufficient for the biosynthesis of amidated polyketides. A novel
      alkaloid (WJ35, or compound 2) was synthesized as the major product when the oxy
      encoded minimal PKS, the C-9 ketoreductase (OxyJ), and OxyD were coexpressed in
      CH999. WJ35 is an isoquinolone compound derived from an amidated decaketide
      backbone and cyclized with novel regioselectivity. The expression of OxyD with a
      heterologous minimal PKS did not afford similarly amidated polyketides,
      suggesting that the oxy-encoded minimal PKS possesses novel starter unit
      specificity.

PMID- 16597961
TI  - Specific growth rate determines the sensitivity of Escherichia coli to thermal,
      UVA, and solar disinfection.
AB  - Knowledge about the sensitivity of the test organism is essential for the
      evaluation of any disinfection method. In this work we show that sensitivity of
      Escherichia coli MG1655 to three physical stresses (mild heat, UVA light, and
      sunlight) that are relevant in the disinfection of drinking water with solar
      radiation is determined by the specific growth rate of the culture. Batch- and
      chemostat-cultivated cells from cultures with similar specific growth rates
      showed similar stress sensitivities. Generally, fast-growing cells were more
      sensitive to the stresses than slow-growing cells. For example, slow-growing
      chemostat-cultivated cells (D = 0.08 h(-1)) and stationary-phase bacteria from
      batch culture that were exposed to mild heat had very similar T(90) (time until
      90% of the population is inactivated) values (T(90, chemostat) = 2.66 h; T(90,
      batch) = 2.62 h), whereas T(90) for cells growing at a mu of 0.9 h(-1) was 0.2 h.
      We present evidence that the stress sensitivity of E. coli is correlated with the
      intracellular level of the alternative sigma factor RpoS. This is also supported
      by the fact that E. coli rpoS mutant cells were more stress sensitive than the
      parent strain by factors of 4.9 (mild heat), 5.3 (UVA light), and 4.1 (sunlight).
      Furthermore, modeling of inactivation curves with GInaFiT revealed that the shape
      of inactivation curves changed depending on the specific growth rate.
      Inactivation curves of cells from fast-growing cultures (mu = 1.0 h(-1)) that
      were irradiated with UVA light showed a tailing effect, while for slow-growing
      cultures (mu = 0.3 h(-1)), inactivation curves with shoulders were obtained. Our
      findings emphasize the need for accurate reporting of specific growth rates and
      detailed culture conditions in disinfection studies to allow comparison of data
      from different studies and laboratories and sound interpretation of the data
      obtained.

PMID- 16597962
TI  - Toxicity and mode of action of Bacillus thuringiensis Cry proteins in the
      Mediterranean corn borer, Sesamia nonagrioides (Lefebvre).
AB  - Sesamia nonagrioides is one of the most damaging pests of corn in Spain and other
      Mediterranean countries. Bt corn expressing the Bacillus thuringiensis Cry1Ab
      toxin is being grown on about 58,000 ha in Spain. Here we studied the mode of
      action of this Cry protein on S. nonagrioides (binding to specific receptors,
      stability of binding, and pore formation) and the modes of action of other Cry
      proteins that were found to be active in this work (Cry1Ac, Cry1Ca, and Cry1Fa).
      Binding assays were performed with (125)I- or biotin-labeled toxins and larval
      brush border membrane vesicles (BBMV). Competition experiments indicated that
      these toxins bind specifically and that Cry1Aa, Cry1Ab, and Cry1Ac share a
      binding site. Cry1Ca and Cry1Fa bind to different sites. In addition, Cry1Fa
      binds to Cry1A's binding site with very low affinity and vice versa. Binding of
      Cry1Ab and Cry1Ac was found to be stable over time, which indicates that the
      observed binding is irreversible. The pore-forming activity of Cry proteins on
      BBMV was determined using the voltage-sensitive fluorescent dye DiSC(3)(5).
      Membrane permeability increased in the presence of the active toxins Cry1Ab and
      Cry1Fa but not in the presence of the nonactive toxin Cry1Da. In terms of
      resistance management, based on our results and the fact that Cry1Ca is not toxic
      to Ostrinia nubilalis, we recommend pyramiding of Cry1Ab with Cry1Fa in the same
      Bt corn plant for better long-term control of corn borers.

PMID- 16597963
TI  - Development of a quantitative assay for mycobacterial endogenous arabinase and
      ensuing studies of arabinase levels and arabinan metabolism in Mycobacterium
      smegmatis.
AB  - Treatment of either Mycobacterium tuberculosis or M. smegmatis with ethambutol
      results both in inhibition of arabinan synthesis and in copious loss of
      previously formed arabinan from the cell wall. The loss of arabinan has been
      shown to be due to the action of an endogenous arabinase. To better understand
      this phenomenon, a quantitative assay for endogenous arabinase was developed.
      Using the assay it was determined that various subcellular fractions of M.
      smegmatis showed significant amounts of endogenous arabinase activity.
      Surprisingly, treatment with ethambutol yielded only minor changes in the amounts
      of endogenous arabinase activities. Endogenous arabinase was present in the cell
      wall, and consistently, incubation of the M. smegmatis cell wall in only buffer
      resulted in the release of arabinan, mimicking the effect of ethambutol on whole
      cells. To determine if cell wall arabinan is rapidly turned over, the arabinan
      was labeled in the early log phase of culture by feeding [(14)C]glucose, followed
      by a "chase" with nonradioactive glucose. Most of the labeled arabinan remained
      in the cell wall after the culture was grown to late log phase. Thus, there is
      active arabinase in the cell wall, but arabinan is not rapidly removed unless
      ethambutol is present. Purification of the endogenous arabinase, using the assay
      described, is ongoing to help further discern its biological function.

PMID- 16597964
TI  - Thiamine-auxotrophic mutants of Pseudomonas fluorescens CHA0 are defective in
      cell-cell signaling and biocontrol factor expression.
AB  - In the biocontrol strain Pseudomonas fluorescens CHA0, the Gac/Rsm signal
      transduction pathway positively controls the synthesis of antifungal secondary
      metabolites and exoenzymes. In this way, the GacS/GacA two-component system
      determines the expression of three small regulatory RNAs (RsmX, RsmY, and RsmZ)
      in a process activated by the strain's own signal molecules, which are not
      related to N-acyl-homoserine lactones. Transposon Tn5 was used to isolate P.
      fluorescens CHA0 insertion mutants that expressed an rsmZ-gfp fusion at reduced
      levels. Five of these mutants were gacS negative, and in them the gacS mutation
      could be complemented for exoproduct and signal synthesis by the gacS wild-type
      allele. Furthermore, two thiamine-auxotrophic (thiC) mutants that exhibited
      decreased signal synthesis in the presence of 5 x 10(-8) M thiamine were found.
      Under these conditions, a thiC mutant grew normally but showed reduced expression
      of the three small RNAs, the exoprotease AprA, and the antibiotic 2,4
      diacetylphloroglucinol. In a gnotobiotic system, a thiC mutant was impaired for
      biological control of Pythium ultimum on cress. Addition of excess exogenous
      thiamine restored all deficiencies of the mutant. Thus, thiamine appears to be an
      important factor in the expression of biological control by P. fluorescens.

PMID- 16597965
TI  - Poly(3-hydroxybutyrate) synthesis by recombinant Escherichia coli arcA mutants in
      microaerobiosis.
AB  - We assessed the effects of different arcA mutations on poly(3-hydroxybutyrate)
      (PHB) synthesis in recombinant Escherichia coli strains carrying the pha
      synthesis genes from Azotobacter sp. strain FA8. The arcA mutations used were an
      internal deletion and the arcA2 allele, a leaky mutation for some of the
      characteristics of the Arc phenotype which confers high respiratory capacity. PHB
      synthesis was not detected in the wild-type strain in shaken flask cultures under
      low-oxygen conditions, while ArcA mutants gave rise to polymer accumulation of up
      to 24% of their cell dry weight. When grown under microaerobic conditions in a
      bioreactor, the arcA deletion mutant reached a PHB content of 27% +/- 2%. Under
      the same conditions, higher biomass and PHB concentrations were observed for the
      strain bearing the arcA2 allele, resulting in a PHB content of 35% +/- 3%. This
      strain grew in a simple medium at a specific growth rate of 0.69 +/- 0.07 h(-1),
      whereas the deletion mutant needed several nutritional additives and showed a
      specific growth rate of 0.56 +/- 0.06 h(-1). The results presented here suggest
      that arcA mutations could play a role in heterologous PHB synthesis in
      microaerobiosis.

PMID- 16597966
TI  - Clonal dissemination of Escherichia coli O157:H7 subtypes among dairy farms in
      northeast Ohio.
AB  - To ascertain the extent to which indistinguishable strains of Escherichia coli
      O157:H7 are shared between farms, molecular characterization was performed on E.
      coli O157:H7 isolates recovered during a longitudinal study of 20 dairy farms in
      northeast Ohio. Of the 20 dairy farms sampled, 16 were located in a primary area
      and 4 were located in two other distant geographical areas. A total of 92 E. coli
      O157:H7 isolates obtained from bovine fecal samples, water trough sediment
      samples, free-stall bedding, and wild-bird excreta samples were characterized.
      Fifty genetic subtypes were observed among the isolates using XbaI and BlnI
      restriction endonucleases. Most restriction endonuclease digestion profiles
      (REDPs) were spatially and temporally clustered. However, four REDPs from
      multiple sources were found to be indistinguishable by pulsed-field gel
      electrophoresis between four pairs of farms. The geographical distance between
      farms which shared an indistinguishable E. coli O157:H7 REDP ranged from 9 to 50
      km, and the on-farm sources sharing indistinguishable REDPs included cattle and
      wild bird feces and free-stall bedding. Within the study population, E. coli
      O157:H7 REDP subtypes were disseminated with considerable frequency among farms
      in close geographic proximity, and nonbovine sources may contribute to the
      transmission of this organism between farms.

PMID- 16597967
TI  - Very low ethanol concentrations affect the viability and growth recovery in post
      stationary-phase Staphylococcus aureus populations.
AB  - Pharmaceuticals, culture media used for in vitro diagnostics and research, human
      body fluids, and environments can retain very low ethanol concentrations (VLEC)
      (< or =0.1%, vol/vol). In contrast to the well-established effects of elevated
      ethanol concentrations on bacteria, little is known about the consequences of
      exposure to VLEC. We supplemented growth media for Staphylococcus aureus strain
      DSM20231 with VLEC (VLEC(+) conditions) and determined ultramorphology, growth,
      and viability compared to those with unsupplemented media (VLEC(-) conditions)
      for prolonged culture times (up to 8 days). VLEC(+)-grown late-stationary-phase
      S. aureus displayed extensive alterations of cell integrity as shown by scanning
      electron microscopy. Surprisingly, while ethanol in the medium was completely
      metabolized during exponential phase, a profound delay of S. aureus post
      stationary-phase recovery (>48 h) was observed. Concomitantly, under VLEC(+)
      conditions, the concentration of acetate in the culture medium remained elevated
      while that of ammonia was reduced, contributing to an acidic culture medium and
      suggesting decreased amino acid catabolism. Interestingly, amino acid depletion
      was not uniformly affected: under VLEC(+) conditions, glutamic acid, ornithine,
      and proline remained in the culture medium while the uptake of other amino acids
      was not affected. Supplementation with arginine, but not with other amino acids,
      was able to restore post-stationary-phase growth and viability. Taken together,
      these data demonstrate that VLEC have profound effects on the recovery of S.
      aureus even after ethanol depletion and delay the transition from primary to
      secondary metabolite catabolism. These data also suggest that the concentration
      of ethanol needed for bacteriostatic control of S. aureus is lower than that
      previously reported.

PMID- 16597968
TI  - Cultivation of denitrifying bacteria: optimization of isolation conditions and
      diversity study.
AB  - An evolutionary algorithm was applied to study the complex interactions between
      medium parameters and their effects on the isolation of denitrifying bacteria,
      both in number and in diversity. Growth media with a pH of 7 and a nitrogen
      concentration of 3 mM, supplemented with 1 ml of vitamin solution but not with
      sodium chloride or riboflavin, were the most successful for the isolation of
      denitrifiers from activated sludge. The use of ethanol or succinate as a carbon
      source and a molar C/N ratio of 2.5, 20, or 25 were also favorable. After testing
      of 60 different medium parameter combinations and comparison with each other as
      well as with the standard medium Trypticase soy agar supplemented with nitrate,
      three growth media were highly suitable for the cultivation of denitrifying
      bacteria. All evaluated isolation conditions were used to study the cultivable
      denitrifier diversity of activated sludge from a municipal wastewater treatment
      plant. One hundred ninety-nine denitrifiers were isolated, the majority of which
      belonged to the Betaproteobacteria (50.4%) and the Alphaproteobacteria (36.8%).
      Representatives of Gammaproteobacteria (5.6%), Epsilonproteobacteria (2%), and
      Firmicutes (4%) and one isolate of the Bacteroidetes were also found. This study
      revealed a much more diverse denitrifying community than that previously
      described in cultivation-dependent research on activated sludge.

PMID- 16597969
TI  - Assessment of the roles of LuxS, S-ribosyl homocysteine, and autoinducer 2 in
      cell attachment during biofilm formation by Listeria monocytogenes EGD-e.
AB  - LuxS is responsible for the production of autoinducer 2 (AI-2), which is involved
      in the quorum-sensing response of Vibrio harveyi. AI-2 is found in several other
      gram-negative and gram-positive bacteria and is therefore considered a good
      candidate for an interspecies communication signal molecule. In order to
      determine if this system is functional in the gastrointestinal pathogen Listeria
      monocytogenes EGD-e, an AI-2 bioassay was performed with culture supernatants.
      The results indicated that this bacterium produces AI-2 like molecules. A
      potential ortholog of V. harveyi luxS, lmo1288, was found by performing sequence
      similarity searches and complementation experiments with Escherichia coli
      DH5alpha, a luxS null strain. lmo1288 was found to be a functional luxS ortholog
      involved in AI-2 synthesis. Indeed, interruption of lmo1288 resulted in loss of
      the AI-2 signal. Although no significant differences were observed between Lux1
      and EGD-e with regard to planktonic growth (at 10 degrees C, 15 degrees C, 25
      degrees C, and 42 degrees C), swimming motility, and phospholipase and hemolytic
      activity, biofilm culture experiments showed that under batch conditions between
      25% and 58% more Lux1 cells than EGD-e cells were attached to the surface
      depending on the incubation time. During biofilm growth in continuous conditions
      after 48 h of culture, Lux1 biofilms were 17 times denser than EGD-e biofilms.
      Finally, our results showed that Lux1 accumulates more S-adenosyl homocysteine
      (SAH) and S-ribosyl homocysteine (SRH) in culture supernatant than the parental
      strain accumulates and that SRH, but not SAH or AI-2, is able to modify the
      number of attached cells.

PMID- 16597970
TI  - The locus coding for the 3-nitrobenzoate dioxygenase of Comamonas sp. strain JS46
      is flanked by IS1071 elements and is subject to deletion and inversion events.
AB  - In Comamonas sp. strain JS46, 3-nitrobenzoate (3Nba) is initially oxidized at the
      3,4 position by a dioxygenase, which results in release of nitrite and production
      of protocatechuate. The locus coding for the 3Nba dioxygenase (designated mnb,
      for m-nitrobenzoate) was mobilized from strain JS46 using a plasmid capture
      method, cloned, and sequenced. The 3Nba dioxygenase (MnbA) is a member of the
      phthalate family of aromatic oxygenases. An open reading frame designated mnbB
      that codes for an NAD(P)H-dependent class IA aromatic oxidoreductase is
      downstream of mnbA. MnbB is tentatively identified as the oxidoreductase that
      transfers reducing equivalents to MnbA in strain JS46. The mnb locus is flanked
      by IS1071 elements. The upstream element is interrupted by a novel insertion
      sequence designated ISCsp1, and the transposase genes of the flanking insertion
      elements are transcribed in the direction opposite the direction of mnbA
      transcription. Spontaneous deletion of mnb occurs because of homologous
      recombination between the directly repeated flanking IS1071 elements. In
      addition, in approximately 0.007 to 0.2% of any population of JS46 cells growing
      on 3Nba, alternative orientations of mnb relative to the flanking IS1071 elements
      are detected. These alternative forms are the result of inversions of mnb and the
      flanking IS1071 elements. Inversions appear to occur because of homologous
      recombination between the inverted repeats that flank the IS1071 elements.

PMID- 16597971
TI  - Genes of Escherichia coli O157:H7 that are involved in high-pressure resistance.
AB  - Seventeen Escherichia coli O157:H7 strains were treated with ultrahigh pressure
      at 500 MPa and 23 +/- 2 degrees C for 1 min. This treatment inactivated 0.6 to
      3.4 log CFU/ml, depending on the strain. The diversity of these strains was
      confirmed by pulsed-field gel electrophoresis (PFGE) analysis, and there was no
      apparent association between PFGE banding patterns and pressure resistance. The
      pressure-resistant strain E. coli O157:H7 EC-88 (0.6-log decrease) and the
      pressure-sensitive strain ATCC 35150 (3.4-log decrease) were treated with a
      sublethal pressure (100 MPa for 15 min at 23 +/- 2 degrees C) and subjected to
      DNA microarray analysis using an E. coli K-12 antisense gene chip. High pressure
      affected the transcription of many genes involved in a variety of intracellular
      mechanisms of EC-88, including the stress response, the thiol-disulfide redox
      system, Fe-S cluster assembly, and spontaneous mutation. Twenty-four E. coli
      isogenic pairs with mutations in the genes regulated by the pressure treatment
      were treated with lethal pressures at 400 MPa and 23 +/- 2 degrees C for 5 min.
      The barotolerance of the mutants relative to that of the wild-type strains helped
      to explain the results obtained by DNA microarray analysis. This study is the
      first report to demonstrate that the expression of Fe-S cluster assembly proteins
      and the fumarate nitrate reductase regulator decreases the resistance to
      pressure, while sigma factor (RpoE), lipoprotein (NlpI), thioredoxin (TrxA),
      thioredoxin reductase (TrxB), a trehalose synthesis protein (OtsA), and a DNA
      binding protein (Dps) promote barotolerance.

PMID- 16597972
TI  - Both msa genes in Renibacterium salmoninarum are needed for full virulence in
      bacterial kidney disease.
AB  - Renibacterium salmoninarum, a gram-positive diplococcobacillus that causes
      bacterial kidney disease among salmon and trout, has two chromosomal loci
      encoding the major soluble antigen (msa) gene. Because the MSA protein is widely
      suspected to be an important virulence factor, we used insertion-duplication
      mutagenesis to generate disruptions of either the msa1 or msa2 gene.
      Surprisingly, expression of MSA protein in broth cultures appeared unaffected.
      However, the virulence of either mutant in juvenile chinook salmon (Oncorhynchus
      tshawytscha) by intraperitoneal challenge was severely attenuated, suggesting
      that disruption of the msa1 or msa2 gene affected in vivo expression.

PMID- 16597973
TI  - Comparison of vertical distributions of prokaryotic assemblages in the anoxic
      Cariaco Basin and Black Sea by use of fluorescence in situ hybridization.
AB  - Individual prokaryotic cells from two major anoxic basins, the Cariaco Basin and
      the Black Sea, were enumerated throughout their water columns using fluorescence
      in situ hybridization (FISH) with the fluorochrome Cy3 or horseradish peroxidase
      modified oligonucleotide probes. For both basins, significant differences in
      total prokaryotic abundance and phylogenetic composition were observed among
      oxic, anoxic, and transitional (redoxcline) waters. Epsilon-proteobacteria,
      Crenarchaeota, and Euryarchaeota were more prevalent in the redoxclines, where
      previous studies reported high rates of chemoautotrophic production relative to
      those in waters above and below the redoxclines. Relative abundances of Archaea
      in both systems varied between 1% and 28% of total prokaryotes, depending on
      depth. The prokaryotic community composition varied between the two anoxic
      basins, consistent with distinct geochemical and physical conditions. In the
      Black Sea, the relative contributions of group I Crenarchaeota (median, 5.5%) to
      prokaryotic communities were significantly higher (P < 0.001; n = 20) than those
      of group II Euryarchaeota (median, 2.9%). In contrast, their proportions were
      nearly equivalent in the Cariaco Basin. Beta-proteobacteria were unexpectedly
      common throughout the Cariaco Basin's water column, accounting for an average of
      47% of 4',6'-diamidino-2-phenylindole (DAPI)-stained cells. This group was below
      the detection limit (<1%) in the Black Sea samples. Compositional differences
      between basins may reflect temporal variability in microbial populations and/or
      systematic differences in environmental conditions and the populations for which
      they select.

PMID- 16597974
TI  - Oligonucleotide array for identification and detection of pythium species.
AB  - A DNA array containing 172 oligonucleotides complementary to specific diagnostic
      regions of internal transcribed spacers (ITS) of more than 100 species was
      developed for identification and detection of Pythium species. All of the species
      studied, with the exception of Pythium ostracodes, exhibited a positive
      hybridization reaction with at least one corresponding species-specific
      oligonucleotide. Hybridization patterns were distinct for each species. The array
      hybridization patterns included cluster-specific oligonucleotides that
      facilitated the recognition of species, including new ones, belonging to groups
      such as those producing filamentous or globose sporangia. BLAST analyses against
      500 publicly available Pythium sequences in GenBank confirmed that species
      specific oligonucleotides were unique to all of the available strains of each
      species, of which there were numerous economically important ones. GenBank
      entries of newly described species that are not putative synonyms showed no
      homology to sequences of the spotted species-specific oligonucleotides, but most
      new species did match some of the cluster-specific oligonucleotides. Further
      verification of the specificity of the DNA array was done with 50 additional
      Pythium isolates obtained by soil dilution plating. The hybridization patterns
      obtained were consistent with the identification of these isolates based on
      morphology and ITS sequence analyses. In another blind test, total DNA of the
      same soil samples was amplified and hybridized on the array, and the results were
      compared to those of 130 Pythium isolates obtained by soil dilution plating and
      root baiting. The 13 species detected by the DNA array corresponded to the
      isolates obtained by a combination of soil dilution plating and baiting, except
      for one new species that was not represented on the array. We conclude that the
      reported DNA array is a reliable tool for identification and detection of the
      majority of Pythium species in environmental samples. Simultaneous detection and
      identification of multiple species of soilborne pathogens such as Pythium species
      could be a major step forward for epidemiological and ecological studies.

PMID- 16597975
TI  - Pseudomonad cyclopentadecanone monooxygenase displaying an uncommon spectrum of
      Baeyer-Villiger oxidations of cyclic ketones.
AB  - Baeyer-Villiger monooxygenases (BVMOs) are biocatalysts that offer the prospect
      of high chemo-, regio-, and enantioselectivity in the organic synthesis of
      lactones or esters from a variety of ketones. In this study, we have cloned,
      sequenced, and overexpressed in Escherichia coli a new BVMO, cyclopentadecanone
      monooxygenase (CpdB or CPDMO), originally derived from Pseudomonas sp. strain HI
      70. The 601-residue primary structure of CpdB revealed only 29% to 50% sequence
      identity to those of known BVMOs. A new sequence motif, characterized by a
      cluster of charged residues, was identified in a subset of BVMO sequences that
      contain an N-terminal extension of approximately 60 to 147 amino acids. The 64
      kDa CPDMO enzyme was purified to apparent homogeneity, providing a specific
      activity of 3.94 micromol/min/mg protein and a 20% yield. CPDMO is monomeric and
      NADPH dependent and contains approximately 1 mol flavin adenine dinucleotide per
      mole of protein. A deletion mutant suggested the importance of the N-terminal 54
      amino acids to CPDMO activity. In addition, a Ser261Ala substitution in a
      Rossmann fold motif resulted in an improved stability and increased affinity of
      the enzyme towards NADPH compared to the wild-type enzyme (K(m) = 8 microM versus
      K(m) = 24 microM). Substrate profiling indicated that CPDMO is unusual among
      known BVMOs in being able to accommodate and oxidize both large and small ring
      substrates that include C(11) to C(15) ketones, methyl-substituted C(5) and C(6)
      ketones, and bicyclic ketones, such as decalone and beta-tetralone. CPDMO has the
      highest affinity (K(m) = 5.8 microM) and the highest catalytic efficiency
      (k(cat)/K(m) ratio of 7.2 x 10(5) M(-1) s(-1)) toward cyclopentadecanone, hence
      the Cpd designation. A number of whole-cell biotransformations were carried out,
      and as a result, CPDMO was found to have an excellent enantioselectivity (E >
      200) as well as 99% S-selectivity toward 2-methylcyclohexanone for the production
      of 7-methyl-2-oxepanone, a potentially valuable chiral building block. Although
      showing a modest selectivity (E = 5.8), macrolactone formation of 15
      hexadecanolide from the kinetic resolution of 2-methylcyclopentadecanone using
      CPDMO was also demonstrated.

PMID- 16597976
TI  - Effects of preculturing conditions on lag time and specific growth rate of
      Enterobacter sakazakii in reconstituted powdered infant formula.
AB  - Enterobacter sakazakii can be present, although in low levels, in dry powdered
      infant formulae, and it has been linked to cases of meningitis in neonates,
      especially those born prematurely. In order to prevent illness, product
      contamination at manufacture and during preparation, as well as growth after
      reconstitution, must be minimized by appropriate control measures. In this
      publication, several determinants of the growth of E. sakazakii in reconstituted
      infant formula are reported. The following key growth parameters were determined:
      lag time, specific growth rate, and maximum population density. Cells were
      harvested at different phases of growth and spiked into powdered infant formula.
      After reconstitution in sterile water, E. sakazakii was able to grow at
      temperatures between 8 and 47 degrees C. The estimated optimal growth temperature
      was 39.4 degrees C, whereas the optimal specific growth rate was 2.31 h(-1). The
      effect of temperature on the specific growth rate was described with two
      secondary growth models. The resulting minimum and maximum temperatures estimated
      with the secondary Rosso equation were 3.6 degrees C and 47.6 degrees C,
      respectively. The estimated lag time varied from 83.3 +/- 18.7 h at 10 degrees C
      to 1.73 +/- 0.43 h at 37 degrees C and could be described with the hyperbolic
      model and reciprocal square root relation. Cells harvested at different phases of
      growth did not exhibit significant differences in either specific growth rate or
      lag time. Strains did not have different lag times, and lag times were short
      given that the cells had spent several (3 to 10) days in dry powdered infant
      formula. The growth rates and lag times at various temperatures obtained in this
      study may help in calculations of the period for which reconstituted infant
      formula can be stored at a specific temperature without detrimental impact on
      health.

PMID- 16597977
TI  - A suppression subtractive hybridization approach reveals niche-specific genes
      that may be involved in predator avoidance in marine Synechococcus isolates.
AB  - Picocyanobacteria of the genus Synechococcus are important contributors to marine
      primary production and are ubiquitous in the world's oceans. This genus is
      genetically diverse, and at least 10 discrete lineages or clades have been
      identified phylogenetically. However, little if anything is known about the
      genetic attributes which characterize particular lineages or are unique to
      specific strains. Here, we used a suppression subtractive hybridization (SSH)
      approach to identify strain- and clade-specific genes in two well-characterized
      laboratory strains, Synechococcus sp. strain WH8103 (clade III) and Synechococcus
      sp. strain WH7803 (clade V). Among the genes that were identified as potentially
      unique to each strain were genes encoding proteins that may be involved in
      specific predator avoidance, including a glycosyltransferase in strain WH8103 and
      a permease component of an ABC-type polysaccharide/polyol phosphate export system
      in WH7803. During this work the genome of one of these strains, WH7803, became
      available. This allowed assessment of the number of false-positive sequences
      (i.e., sequences present in the tester genome) present among the SSH-enriched
      sequences. We found that approximately 9% of the WH8103 sequences were potential
      false-positive sequences, which demonstrated that caution should be used when
      this technology is used to assess genomic differences in genetically similar
      bacterial strains.

PMID- 16597978
TI  - Identification of Sinorhizobium meliloti early symbiotic genes by use of a
      positive functional screen.
AB  - The soil bacterium Sinorhizobium meliloti establishes nitrogen-fixing symbiosis
      with its leguminous host plant, alfalfa, following a series of continuous signal
      exchanges. The complexity of the changes of alfalfa root structures during
      symbiosis and the amount of S. meliloti genes with unknown functions raised the
      possibility that more S. meliloti genes may be required for early stages of the
      symbiosis. A positive functional screen of the entire S. meliloti genome for
      symbiotic genes was carried out using a modified in vivo expression technology. A
      group of genes and putative genes were found to be expressed in early stages of
      the symbiosis, and 23 of them were alfalfa root exudate inducible. These 23 genes
      were further separated into two groups based on their responses to apigenin, a
      known nodulation (nod) gene inducer. The group of six genes not inducible by
      apigenin included the lsrA gene, which is essential for the symbiosis, and the
      dgkA gene, which is involved in the synthesis of cyclic beta-1,2-glucan required
      for the S. meliloti-alfalfa symbiosis. In the group of 17 apigenin-inducible
      genes, most have not been previously characterized in S. meliloti, and none of
      them belongs to the nod gene family. The identification of this large group of
      alfalfa root exudate-inducible S. meliloti genes suggests that the interactions
      in the early stages of the S. meliloti and alfalfa symbiosis could be complex and
      that further characterization of these genes will lead to a better understanding
      of the symbiosis.

PMID- 16597979
TI  - Detection of norovirus capsid protein in authentic standards and in stool
      extracts by matrix-assisted laser desorption ionization and nanospray mass
      spectrometry.
AB  - Mass spectrometry (MS) represents a rapid technique for the identification of
      microbial monocultures, and its adaptation to the detection of pathogens in real
      world samples is a public health and homeland security priority. Norovirus, a
      leading cause of gastroenteritis in the world, is difficult to monitor because it
      cannot be cultured outside the human body. The detection of norovirus capsid
      protein was explored using three common MS-based methods: scanning of intact
      proteins, peptide mass fingerprinting, and peptide sequencing. Detection of
      intact target protein was limited by poor selectivity and sensitivity. Detection
      of up to 16 target peptides by peptide mass fingerprinting allowed for the
      reproducible and confident (P < 0.05) detection of the 56-kDa norovirus capsid
      protein in the range of 0.1 x 10(-12) to 50 x 10(-12) mol in authentic standards
      of recombinant norovirus virus-like particles (VLPs). To explore assay
      performance in complex matrixes, a non-gel-based, rapid method (2 to 3 h) for
      virus extraction from human stool was evaluated (72% +/- 12% recovery), and
      additional analyses were performed on norovirus-free stool extracts fortified
      with VLPs. Whereas peptide mass fingerprinting was rendered impractical by sample
      interferences, peptide sequencing using nanospray tandem MS facilitated
      unambiguous identification of > or =250 fmol of capsid protein in stool extracts.
      This is the first report on MS-based detection of norovirus, accomplished by
      using structurally identical, noninfective VLPs at clinically relevant
      concentrations. It represents an important milestone in the development of assays
      for surveillance of this category B bioterrorism agent.

PMID- 16597980
TI  - Specific bacterial, archaeal, and eukaryotic communities in tidal-flat sediments
      along a vertical profile of several meters.
AB  - The subsurface of a tidal-flat sediment was analyzed down to 360 cm in depth by
      molecular and geochemical methods. A community structure analysis of all three
      domains of life was performed using domain-specific PCR followed by denaturing
      gradient gel electrophoresis analysis and sequencing of characteristic bands. The
      sediment column comprised horizons easily distinguishable by lithology that were
      deposited in intertidal and salt marsh environments. The pore water profile was
      characterized by a subsurface sulfate peak at a depth of about 250 cm. Methane
      and sulfate profiles were opposed, showing increased methane concentrations in
      the sulfate-free layers. The availability of organic carbon appeared to have the
      most pronounced effect on the bacterial community composition in deeper sediment
      layers. In general, the bacterial community was dominated by fermenters and
      syntrophic bacteria. The depth distribution of methanogenic archaea correlated
      with the sulfate profile and could be explained by electron donor competition
      with sulfate-reducing bacteria. Sequences affiliated with the typically
      hydrogenotrophic Methanomicrobiales were present in sulfate-free layers. Archaea
      belonging to the Methanosarcinales that utilize noncompetitive substrates were
      found along the entire anoxic-sediment column. Primers targeting the eukaryotic
      18S rRNA gene revealed the presence of a subset of archaeal sequences in the
      deeper part of the sediment cores. The phylogenetic distance to other archaeal
      sequences indicates that these organisms represent a new phylogenetic group,
      proposed as "tidal-flat cluster 1." Eukarya were still detectable at 360 cm, even
      though their diversity decreased with depth. Most of the eukaryotic sequences
      were distantly related to those of grazers and deposit feeders.

PMID- 16597981
TI  - Quantitative PCR targeting 16S rRNA and reductive dehalogenase genes
      simultaneously monitors multiple Dehalococcoides strains.
AB  - The 16S rRNA gene provides insufficient information to infer the range of
      chloroorganic electron acceptors used by different Dehalococcoides organisms. To
      overcome this limitation and provide enhanced diagnostic tools for growth
      measurements, site assessment, and bioremediation monitoring, a quantitative real
      time PCR (qPCR) approach targeting 16S rRNA genes and three Dehalococcoides
      reductive dehalogenase (RDase) genes with assigned function (i.e., tceA, bvcA,
      and vcrA) was designed and evaluated. qPCR standard curves generated for the
      RDase genes by use of genomic DNA from Dehalococcoides pure cultures correlated
      with standard curves obtained for both Bacteria- and Dehalococcoides-targeted 16S
      rRNA genes, suggesting that the RDase genes are useful targets for quantitative
      assessment of Dehalococcoides organisms. RDase gene probe/primer pairs were
      specific for the Dehalococcoides strains known to carry the diagnostic RDase gene
      sequences, and the qPCR method allowed the detection of as few as 1 to 20 and
      quantification of as few as 50 to 100 tceA, bvcA, or vcrA gene targets per PCR
      volume. The qPCR approach was applied to dechlorinating enrichment cultures,
      microcosms, and samples from a contaminated site. In characterized enrichment
      cultures where known Dehalococcoides strains were enumerated, the sum of the
      three RDase genes equaled the total Dehalococcoides cell numbers. In site samples
      and chloroethane-dechlorinating microcosms, the sum of the three RDase genes was
      much less than that predicted by Dehalococcoides-targeted qPCR, totaling 10 to
      30% of the total Dehalococcoides cell numbers. Hence, a large number of
      Dehalococcoides spp. contain as-yet-unidentified RDase genes, indicating that our
      current understanding of the dechlorinating Dehalococcoides community is
      incomplete.

PMID- 16597982
TI  - Geobacter lovleyi sp. nov. strain SZ, a novel metal-reducing and
      tetrachloroethene-dechlorinating bacterium.
AB  - A bacterial isolate, designated strain SZ, was obtained from noncontaminated
      creek sediment microcosms based on its ability to derive energy from acetate
      oxidation coupled to tetrachloroethene (PCE)-to-cis-1,2-dichloroethene (cis-DCE)
      dechlorination (i.e., chlororespiration). Hydrogen and pyruvate served as
      alternate electron donors for strain SZ, and the range of electron acceptors
      included (reduced products are given in brackets) PCE and trichloroethene [cis
      DCE], nitrate [ammonium], fumarate [succinate], Fe(III) [Fe(II)], malate
      [succinate], Mn(IV) [Mn(II)], U(VI) [U(IV)], and elemental sulfur [sulfide]. PCE
      and soluble Fe(III) (as ferric citrate) were reduced at rates of 56.5 and 164
      nmol min(-1) mg of protein(-1), respectively, with acetate as the electron donor.
      Alternate electron acceptors, such as U(VI) and nitrate, did not inhibit PCE
      dechlorination and were consumed concomitantly. With PCE, Fe(III) (as ferric
      citrate), and nitrate as electron acceptors, H(2) was consumed to threshold
      concentrations of 0.08 +/- 0.03 nM, 0.16 +/- 0.07 nM, and 0.5 +/- 0.06 nM,
      respectively, and acetate was consumed to 3.0 +/- 2.1 nM, 1.2 +/- 0.5 nM, and 3.6
      +/- 0.25 nM, respectively. Apparently, electron acceptor-specific acetate
      consumption threshold concentrations exist, suggesting that similar to the
      hydrogen threshold model, the measurement of acetate threshold concentrations
      offers an additional diagnostic tool to delineate terminal electron-accepting
      processes in anaerobic subsurface environments. Genetic and phenotypic analyses
      classify strain SZ as the type strain of the new species, Geobacter lovleyi sp.
      nov., with Geobacter (formerly Trichlorobacter) thiogenes as the closest
      relative. Furthermore, the analysis of 16S rRNA gene sequences recovered from PCE
      dechlorinating consortia and chloroethene-contaminated subsurface environments
      suggests that Geobacter lovleyi belongs to a distinct, dechlorinating clade
      within the metal-reducing Geobacter group. Substrate versatility, consumption of
      electron donors to low threshold concentrations, and simultaneous reduction of
      electron acceptors suggest that strain SZ-type organisms have desirable
      characteristics for bioremediation applications.

PMID- 16597983
TI  - Chlorophenol hydroxylases encoded by plasmid pJP4 differentially contribute to
      chlorophenoxyacetic acid degradation.
AB  - Phenoxyalkanoic compounds are used worldwide as herbicides. Cupriavidus necator
      JMP134(pJP4) catabolizes 2,4-dichlorophenoxyacetate (2,4-D) and 4-chloro-2
      methylphenoxyacetate (MCPA), using tfd functions carried on plasmid pJP4. TfdA
      cleaves the ether bonds of these herbicides to produce 2,4-dichlorophenol (2,4
      DCP) and 4-chloro-2-methylphenol (MCP), respectively. These intermediates can be
      degraded by two chlorophenol hydroxylases encoded by the tfdB(I) and tfdB(II)
      genes to produce the respective chlorocatechols. We studied the specific
      contribution of each of the TfdB enzymes to the 2,4-D/MCPA degradation pathway.
      To accomplish this, the tfdB(I) and tfdB(II) genes were independently
      inactivated, and growth on each chlorophenoxyacetate and total chlorophenol
      hydroxylase activity were measured for the mutant strains. The phenotype of these
      mutants shows that both TfdB enzymes are used for growth on 2,4-D or MCPA but
      that TfdB(I) contributes to a significantly higher extent than TfdB(II). Both
      enzymes showed similar specificity profiles, with 2,4-DCP, MCP, and 4
      chlorophenol being the best substrates. An accumulation of chlorophenol was found
      to inhibit chlorophenoxyacetate degradation, and inactivation of the tfdB genes
      enhanced the toxic effect of 2,4-DCP on C. necator cells. Furthermore, increased
      chlorophenol production by overexpression of TfdA also had a negative effect on
      2,4-D degradation by C. necator JMP134 and by a different host, Burkholderia
      xenovorans LB400, harboring plasmid pJP4. The results of this work indicate that
      codification and expression of the two tfdB genes in pJP4 are important to avoid
      toxic accumulations of chlorophenols during phenoxyacetic acid degradation and
      that a balance between chlorophenol-producing and chlorophenol-consuming
      reactions is necessary for growth on these compounds.

PMID- 16597984
TI  - Molecular population genetics and phenotypic diversification of two populations
      of the thermophilic cyanobacterium Mastigocladus laminosus.
AB  - We investigated the distributions of genetic and phenotypic variation for two
      Yellowstone National Park populations of the heterocyst-forming cyanobacterium
      Mastigocladus (Fischerella) laminosus that exhibit dramatic phenotypic
      differences as a result of environmental differences in nitrogen availability.
      One population develops heterocysts and fixes nitrogen in situ in response to a
      deficiency of combined nitrogen in its environment, whereas the other population
      does neither due to the availability of a preferred nitrogen source. Slowly
      evolving molecular markers, including the 16S rRNA gene and the downstream
      internal transcribed spacer, are identical among all laboratory isolates from
      both populations but belie considerable genetic and phenotypic diversity. The
      total nucleotide diversity at six nitrogen metabolism loci was roughly three
      times greater than that observed for the human global population. The two
      populations are genetically differentiated, although variation in performance on
      different nitrogen sources among genotypes could not be explained by local
      adaptation to available nitrogen in the respective environments. Population
      genetic models suggest that local adaptation is mutation limited but also that
      the populations are expected to continue to diverge due to low migratory gene
      flow.

PMID- 16597985
TI  - Quantitative real-time Legionella PCR for environmental water samples: data
      interpretation.
AB  - Quantitative Legionella PCRs targeting the 16S rRNA gene (specific for the genus
      Legionella) and the mip gene (specific for the species Legionella pneumophila)
      were applied to a total of 223 hot water system samples (131 in one laboratory
      and 92 in another laboratory) and 37 cooling tower samples (all in the same
      laboratory). The PCR results were compared with those of conventional culture.
      16S rRNA gene PCR results were nonquantifiable for 2.8% of cooling tower samples
      and up to 39.1% of hot water system samples, and this was highly predictive of
      Legionella CFU counts below 250/liter. PCR cutoff values for identifying hot
      water system samples containing >10(3) CFU/liter legionellae were determined
      separately in each laboratory. The cutoffs differed widely between the
      laboratories and had sensitivities from 87.7 to 92.9% and specificities from 77.3
      to 96.5%. The best specificity was obtained with mip PCR. PCR cutoffs could not
      be determined for cooling tower samples, as the results were highly variable and
      often high for culture-negative samples. Thus, quantitative Legionella PCR
      appears to be applicable to samples from hot water systems, but the positivity
      cutoff has to be determined in each laboratory.

PMID- 16597986
TI  - Lipid II-based antimicrobial activity of the lantibiotic plantaricin C.
AB  - We analyzed the mode of action of the lantibiotic plantaricin C (PlnC), produced
      by Lactobacillus plantarum LL441. Compared to the well-characterized type A
      lantibiotic nisin and type B lantibiotic mersacidin, which are both able to
      interact with the cell wall precursor lipid II, PlnC displays structural features
      of both prototypes. In this regard, we found that lipid II plays a key role in
      the antimicrobial activity of PlnC besides that of pore formation. The pore
      forming activity of PlnC in whole cells was prevented by shielding lipid II on
      the cell surface. However, in contrast to nisin, PlnC was not able to
      permeabilize Lactococcus lactis cells or to form pores in 1,2-dioleoyl-sn-glycero
      3-phosphocholine liposomes supplemented with 0.1 mol% purified lipid II. This
      emphasized the different requirements of these lantibiotics for pore formation.
      Using cell wall synthesis assays, we identified PlnC as a potent inhibitor of (i)
      lipid II synthesis and (ii) the FemX reaction, i.e., the addition of the first
      Gly to the pentapeptide side chain of lipid II. As revealed by thin-layer
      chromatography, both reactions were clearly blocked by the formation of a PlnC
      lipid I and/or PlnC-lipid II complex. On the basis of the in vivo and in vitro
      activities of PlnC shown in this study and the structural lipid II binding motifs
      described for other lantibiotics, the specific interaction of PlnC with lipid II
      is discussed.

PMID- 16597987
TI  - Characterization of intestinal microbiota and response to dietary virginiamycin
      supplementation in the broiler chicken.
AB  - The inclusion of antibiotic growth promoters, such as virginiamycin, at
      subtherapeutic levels in poultry feeds has a positive effect on health and growth
      characteristics, possibly due to beneficial effects on the host gastrointestinal
      microbiota. To improve our understanding of the chicken gastrointestinal
      microbiota and the effect of virginiamycin on its composition, we characterized
      the bacteria found in five different gastrointestinal tract locations (duodenal
      loop, mid-jejunum, proximal ileum, ileocecal junction, and cecum) in 47-day-old
      chickens that were fed diets excluding or including virginiamycin throughout the
      production cycle. Ten libraries (five gastrointestinal tract locations from two
      groups of birds) of approximately 555-bp chaperonin 60 PCR products were
      prepared, and 10,932 cloned sequences were analyzed. A total of 370 distinct
      cpn60 sequences were identified, which ranged in frequency of recovery from 1 to
      2,872. The small intestinal libraries were dominated by sequences from the
      Lactobacillales (90% of sequences), while the cecum libraries were more diverse
      and included members of the Clostridiales (68%), Lactobacillales (25%), and
      Bacteroidetes (6%). To assess the effects of virginiamycin on the
      gastrointestinal microbiota, 15 bacterial targets were enumerated using
      quantitative, real-time PCR. Virginiamycin was associated with increased
      abundance of many of the targets in the proximal gastrointestinal tract (duodenal
      loop to proximal ileum), with fewer targets affected in the distal regions
      (ileocecal junction and cecum). These findings provide improved profiling of the
      composition of the chicken intestinal microbiota and indicate that microbial
      responses to virginiamycin are most significant in the proximal small intestine.

PMID- 16597988
TI  - Sequencing and heterologous expression of an epimerase and two lyases from
      iminodisuccinate-degrading bacteria.
AB  - Recently, degradation of all existing epimers of the complexing agent
      iminodisuccinate (IDS) in the bacterial strain Agrobacterium tumefaciens BY6 was
      proven to depend on an epimerase and a C-N lyase (Cokesa et al., Appl. Environ.
      Microbiol. 70:3941-3947, 2004). In the bacterial strain Ralstonia sp. strain
      SLRS7, a corresponding C-N lyase is responsible for the initial degradation step
      (Cokesa et al., Biodegradation 15:229-239, 2004). The ite gene, encoding the IDS
      transforming epimerase, and the genes icl(B) and icl(S), encoding the IDS
      converting BY6-lyase and SLRS7-lyase, respectively, were cloned and sequenced.
      The epimerase gene encodes a protein with a predicted subunit molecular mass of
      47.6 kDa. The highest degree of epimerase amino acid sequence identities was
      found with proteins of unknown function, indicating a novel protein. For the
      lyases, the deduced amino acid sequences show high similarity to enzymes of the
      fumarase II family. A classification into a new subfamily within the enzyme
      family is proposed. The subunit molecular masses of the lyases were calculated to
      be 54.4 and 54.7 kDa, respectively. In Agrobacterium tumefaciens BY6, the ite
      gene was on an approximately 180-kb circular plasmid, whereas the icl(B) gene was
      chromosomal like the corresponding icl(S) gene in Ralstonia sp. strain SLRS7.
      Heterologous expression in Escherichia coli and subsequent purification revealed
      recombinant enzymes with in vitro activity similar to that of the corresponding
      enzymes from the wild-type strains.

PMID- 16597989
TI  - Identification of Salmonella enterica serovar Typhimurium genes important for
      survival in the swine gastric environment.
AB  - Since the stomach is a first line of defense for the host against ingested
      microorganisms, an ex vivo swine stomach contents (SSC) assay was developed to
      search for genes important for Salmonella enterica serovar Typhimurium survival
      in the hostile gastric environment. Initial characterization of the SSC assay (pH
      3.87) using previously identified, acid-sensitive serovar Typhimurium mutants
      revealed a 10-fold decrease in survival for a phoP mutant following 20 min of
      challenge and no survival for mutants of rpoS or fur. To identify additional
      genes, a signature-tagged mutagenesis bank was constructed and screened in the
      SSC assay. Nineteen mutants were identified and individually analyzed in the SSC
      and acid tolerance response assays; 13 mutants exhibited a 10-fold or greater
      sensitivity in the SSC assay compared to the wild-type strain, but only 3 mutants
      displayed a 10-fold or greater decrease in survival following pH 3.0 acidic
      challenge. Further examination determined that the lethal effects of the SSC are
      pH dependent but that low pH is not the sole killing mechanism(s). Gas
      chromatography analysis of the SSC revealed lactic acid levels of 126 mM. Upon
      investigating the effects of lactic acid on serovar Typhimurium survival in a
      synthetic gastric fluid, not only was a concentration- and time-dependent lethal
      effect observed, but the phoP, rpoS, fur, and pnp genes were identified as
      involved in protection against lactic acid exposure. These studies indicate a
      role in gastric survival for several serovar Typhimurium genes and imply that the
      stomach environment is defined by more than low pH.

PMID- 16597991
TI  - Toxigenic Vibrio cholerae in the aquatic environment of Mathbaria, Bangladesh.
AB  - Toxigenic Vibrio cholerae, rarely isolated from the aquatic environment between
      cholera epidemics, can be detected in what is now understood to be a dormant
      stage, i.e., viable but nonculturable when standard bacteriological methods are
      used. In the research reported here, biofilms have proved to be a source of
      culturable V. cholerae, even in nonepidemic periods. Biweekly environmental
      surveillance for V. cholerae was carried out in Mathbaria, an area of cholera
      endemicity adjacent to the Bay of Bengal, with the focus on V. cholerae O1 and
      O139 Bengal. A total of 297 samples of water, phytoplankton, and zooplankton were
      collected between March and December 2004, yielding eight V. cholerae O1 and four
      O139 Bengal isolates. A combination of culture methods, multiplex-PCR, and direct
      fluorescent antibody (DFA) counting revealed the Mathbaria aquatic environment to
      be a reservoir for V. cholerae O1 and O139 Bengal. DFA results showed significant
      clumping of the bacteria during the interepidemic period for cholera, and the
      fluorescent micrographs revealed large numbers of V. cholerae O1 in thin films of
      exopolysaccharides (biofilm). A similar clumping of V. cholerae O1 was also
      observed in samples collected from Matlab, Bangladesh, where cholera also is
      endemic. Thus, the results of the study provided in situ evidence for V. cholerae
      O1 and O139 in the aquatic environment, predominantly as viable but nonculturable
      cells and culturable cells in biofilm consortia. The biofilm community is
      concluded to be an additional reservoir of cholera bacteria in the aquatic
      environment between seasonal epidemics of cholera in Bangladesh.

PMID- 16597990
TI  - Molecular characterization of subject-specific oral microflora during initial
      colonization of enamel.
AB  - The initial microbial colonization of tooth surfaces is a repeatable and
      selective process, with certain bacterial species predominating in the nascent
      biofilm. Characterization of the initial microflora is the first step in
      understanding interactions among community members that shape ensuing biofilm
      development. Using molecular methods and a retrievable enamel chip model, we
      characterized the microbial diversity of early dental biofilms in three subjects.
      A total of 531 16S rRNA gene sequences were analyzed, and 97 distinct phylotypes
      were identified. Microbial community composition was shown to be statistically
      different among subjects. In all subjects, however, 4-h and 8-h communities were
      dominated by Streptococcus spp. belonging to the Streptococcus
      oralis/Streptococcus mitis group. Other frequently observed genera (comprising at
      least 5% of clone sequences in at least one of the six clone libraries) were
      Actinomyces, Gemella, Granulicatella, Neisseria, Prevotella, Rothia, and
      Veillonella. Fluorescence in situ hybridization (FISH) confirmed that the
      proportion of Streptococcus sp. sequences in the clone libraries coincided with
      the proportion of streptococcus probe-positive organisms on the chip. FISH also
      revealed that, in the undisturbed plaque, not only Streptococcus spp. but also
      the rarer Prevotella spp. were usually seen in small multigeneric clusters of
      cells. This study shows that the initial dental plaque community of each subject
      is unique in terms of diversity and composition. Repetitive and distinctive
      community composition within subjects suggests that the spatiotemporal
      interactions and ecological shifts that accompany biofilm maturation also occur
      in a subject-dependent manner.

PMID- 16597992
TI  - Bacillus endospores isolated from granite: close molecular relationships to
      globally distributed Bacillus spp. from endolithic and extreme environments.
AB  - As part of an ongoing effort to catalog spore-forming bacterial populations in
      environments conducive to interplanetary transfer by natural impacts or by human
      spaceflight activities, spores of Bacillus spp. were isolated and characterized
      from the interior of near-subsurface granite rock collected from the Santa
      Catalina Mountains, AZ. Granite was found to contain approximately 500 cultivable
      Bacillus spores and approximately 10(4) total cultivable bacteria per gram. Many
      of the Bacillus isolates produced a previously unreported diffusible blue
      fluorescent compound. Two strains of eight tested exhibited increased spore UV
      resistance relative to a standard Bacillus subtilis UV biodosimetry strain. Fifty
      six isolates were identified by repetitive extragenic palindromic PCR (rep-PCR)
      and 16S rRNA gene analysis as most closely related to B. megaterium (15
      isolates), B. simplex (23 isolates), B. drentensis (6 isolates), B. niacini (7
      isolates), and, likely, a new species related to B. barbaricus (5 isolates).
      Granite isolates were very closely related to a limited number of Bacillus spp.
      previously found to inhabit (i) globally distributed endolithic sites such as
      biodeteriorated murals, stone tombs, underground caverns, and rock concretions
      and (ii) extreme environments such as Antarctic soils, deep sea floor sediments,
      and spacecraft assembly facilities. Thus, it appears that the occurrence of
      Bacillus spp. in endolithic or extreme environments is not accidental but that
      these environments create unique niches excluding most Bacillus spp. but to which
      a limited number of Bacillus spp. are specifically adapted.

PMID- 16597993
TI  - Characterization of biofilm formation by clinically relevant serotypes of group A
      streptococci.
AB  - Streptococcus pyogenes (group A streptococcus [GAS]) is a frequent cause of
      purulent infections in humans. As potentially important aspects of its
      pathogenicity, GAS was recently shown to aggregate, form intratissue
      microcolonies, and potentially participate in multispecies biofilms. In this
      study, we show that GAS in fact forms monospecies biofilms in vitro, and we
      analyze the basic parameters of S. pyogenes in vitro biofilm formation, using
      Streptococcus epidermidis as a biofilm-positive control. Of nine clinically
      important serotype strains, M2, M6, M14, and M18 were found to significantly
      adhere to coated and uncoated polystyrene surfaces. Fibronectin and collagen
      types I and IV best supported primary adherence of serotype M2 and M18 strains,
      respectively, whereas serotype M6 and M14 strains strongly bound to uncoated
      polystyrene surfaces. Absorption measurements of safranin staining, as well as
      electron scanning and confocal laser scanning microscopy, documented that primary
      adherence led to subsequent formation of three-dimensional biofilm structures
      consisting of up to 46 bacterial layers. Of note, GAS isolates belonging to the
      same serotype were found to be very heterogeneous in their biofilm-forming
      behavior. Biofilm formation was equally efficient under static and continuous
      flow conditions and consisted of the classical three steps, including partial
      disintegration after long-term incubation. Activity of the SilC signaling peptide
      as a component of a putative quorum-sensing system was found to influence the
      biofilm structure and density of serotype M14 and M18 strains. Based on the
      presented methods and results, standardized analyses of GAS biofilms and their
      impact on GAS pathogenicity are now feasible.

PMID- 16597994
TI  - Novel luciferase reporter system for in vitro and organ-specific monitoring of
      differential gene expression in Listeria monocytogenes.
AB  - In this paper we describe construction of a luciferase-based vector, pPL2lux, and
      use of this vector to study gene expression in Listeria monocytogenes. pPL2lux is
      a derivative of the listerial integration vector pPL2 and harbors a synthetic
      luxABCDE operon encoding a fatty acid reductase complex (LuxCDE) involved in
      synthesis of the fatty aldehyde substrate for the bioluminescence reaction
      catalyzed by the LuxAB luciferase. We constructed pPL2lux derivatives in which
      the secA and hlyA promoters were translationally fused to luxABCDE and integrated
      as a single copy into the chromosome of L. monocytogenes EGD-e. Growth
      experiments revealed that hlyA was expressed predominantly in the stationary
      phase in LB medium buffered at pH 7.4, whereas secA expression could be detected
      in the exponential growth phase. Moreover, the correlation between luciferase
      activity and transcription levels, as determined by reverse transcriptase PCR,
      was confirmed using conditions known to lead to repression and activation of
      hemolysin expression (addition of cellobiose and activated charcoal,
      respectively). Furthermore, hemolysin expression could be monitored in real time
      during invasion of an intact monolayer of C2Bbe1 (Caco-2-derived) cells. Finally,
      hemolysin expression could be detected in the livers, spleens, and kidneys of
      mice 3 days postinfection. These experiments clearly established the
      effectiveness of pPL2lux as a quantitative reporter system for real-time,
      noninvasive evaluation of gene expression in L. monocytogenes.

PMID- 16597995
TI  - Planktonic replication is essential for biofilm formation by Legionella
      pneumophila in a complex medium under static and dynamic flow conditions.
AB  - Legionella pneumophila persists for a long time in aquatic habitats, where the
      bacteria associate with biofilms and replicate within protozoan predators. While
      L. pneumophila serves as a paradigm for intracellular growth within protozoa, it
      is less clear whether the bacteria form or replicate within biofilms in the
      absence of protozoa. In this study, we analyzed surface adherence of and biofilm
      formation by L. pneumophila in a rich medium that supported axenic replication.
      Biofilm formation by the virulent L. pneumophila strain JR32 and by clinical and
      environmental isolates was analyzed by confocal microscopy and crystal violet
      staining. Strain JR32 formed biofilms on glass surfaces and upright polystyrene
      wells, as well as on pins of "inverse" microtiter plates, indicating that biofilm
      formation was not simply due to sedimentation of the bacteria. Biofilm formation
      by an L. pneumophila fliA mutant lacking the alternative sigma factor sigma(28)
      was reduced, which demonstrated that bacterial factors are required. Accumulation
      of biomass coincided with an increase in the optical density at 600 nm and ceased
      when the bacteria reached the stationary growth phase. L. pneumophila neither
      grew nor formed biofilms in the inverse system if the medium was exchanged twice
      a day. However, after addition of Acanthamoeba castellanii, the bacteria
      proliferated and adhered to surfaces. Sessile (surface-attached) and planktonic
      (free-swimming) L. pneumophila expressed beta-galactosidase activity to similar
      extents, and therefore, the observed lack of proliferation of surface-attached
      bacteria was not due to impaired protein synthesis or metabolic activity.
      Cocultivation of green fluorescent protein (GFP)- and DsRed-labeled L.
      pneumophila led to randomly interspersed cells on the substratum and in
      aggregates, and no sizeable patches of clonally growing bacteria were observed.
      Our findings indicate that biofilm formation by L. pneumophila in a rich medium
      is due to growth of planktonic bacteria rather than to growth of sessile
      bacteria. In agreement with this conclusion, GFP-labeled L. pneumophila initially
      adhered in a continuous-flow chamber system but detached over time; the
      detachment correlated with the flow rate, and there was no accumulation of
      biomass. Under these conditions, L. pneumophila persisted in biofilms formed by
      Empedobacter breve or Microbacterium sp. but not in biofilms formed by Klebsiella
      pneumoniae or other environmental bacteria, suggesting that specific interactions
      between the bacteria modulate adherence.

PMID- 16597996
TI  - Anaerobic ammonium-oxidizing (anammox) bacteria and associated activity in fixed
      film biofilters of a marine recirculating aquaculture system.
AB  - Microbial communities in the biological filter and waste sludge compartments of a
      marine recirculating aquaculture system were examined to determine the presence
      and activity of anaerobic ammonium-oxidizing (anammox) bacteria. Community DNA
      was extracted from aerobic and anaerobic fixed-film biofilters and the anaerobic
      sludge waste collection tank and was analyzed by amplifying 16S rRNA genes by PCR
      using anammox-selective and universal GC-clamped primers. Separation of amplified
      PCR products by denaturing gradient gel electrophoresis and sequencing of the
      different phylotypes revealed a diverse biofilter microbial community. While
      Planctomycetales were found in all three communities, the anaerobic denitrifying
      biofilters contained one clone that exhibited high levels of sequence similarity
      to known anammox bacteria. Fluorescence in situ hybridization studies using an
      anammox-specific probe confirmed the presence of anammox Planctomycetales in the
      microbial biofilm from the denitrifying biofilters, and anammox activity was
      observed in these biofilters, as detected by the ability to simultaneously
      consume ammonia and nitrite. To our knowledge, this is the first identification
      of anammox-related sequences in a marine recirculating aquaculture filtration
      system, and our findings provide a foundation for incorporating this important
      pathway for complete nitrogen removal in such systems.

PMID- 16597997
TI  - Diversity and biocatalytic potential of epoxide hydrolases identified by genome
      analysis.
AB  - Epoxide hydrolases play an important role in the biodegradation of organic
      compounds and are potentially useful in enantioselective biocatalysis. An
      analysis of various genomic databases revealed that about 20% of sequenced
      organisms contain one or more putative epoxide hydrolase genes. They were found
      in all domains of life, and many fungi and actinobacteria contain several
      putative epoxide hydrolase-encoding genes. Multiple sequence alignments of
      epoxide hydrolases with other known and putative alpha/beta-hydrolase fold
      enzymes that possess a nucleophilic aspartate revealed that these enzymes can be
      classified into eight phylogenetic groups that all contain putative epoxide
      hydrolases. To determine their catalytic activities, 10 putative bacterial
      epoxide hydrolase genes and 2 known bacterial epoxide hydrolase genes were cloned
      and overexpressed in Escherichia coli. The production of active enzyme was
      strongly improved by fusion to the maltose binding protein (MalE), which
      prevented inclusion body formation and facilitated protein purification. Eight of
      the 12 fusion proteins were active toward one or more of the 21 epoxides that
      were tested, and they converted both terminal and nonterminal epoxides. Four of
      the new epoxide hydrolases showed an uncommon enantiopreference for meso-epoxides
      and/or terminal aromatic epoxides, which made them suitable for the production of
      enantiopure (S,S)-diols and (R)-epoxides. The results show that the expression of
      epoxide hydrolase genes that are detected by analyses of genomic databases is a
      useful strategy for obtaining new biocatalysts.

PMID- 16597998
TI  - Overexpression and characterization of an iron storage and DNA-binding Dps
      protein from Trichodesmium erythraeum.
AB  - Although the role of iron in marine productivity has received a great deal of
      attention, no iron storage protein has been isolated from a marine microorganism
      previously. We describe an Fe-binding protein belonging to the Dps family (DNA
      binding protein from starved cells) in the N(2)-fixing marine cyanobacterium
      Trichodesmium erythraeum. A dps gene encoding a protein with significant levels
      of identity to members of the Dps family was identified in the genome of T.
      erythraeum. This gene codes for a putative Dps(T. erythraeurm) protein
      (Dps(tery)) with 69% primary amino acid sequence similarity to Synechococcus
      DpsA. We expressed and purified Dps(tery), and we found that Dps(tery), like
      other Dps proteins, is able to bind Fe and DNA and protect DNA from degradation
      by DNase. We also found that Dps(tery) binds phosphate, like other ferritin
      family proteins. Fe K near-edge X-ray absorption of Dps(tery) indicated that it
      has an iron core that resembles that of horse spleen ferritin.

PMID- 16597999
TI  - Reduction of soluble and insoluble iron forms by membrane fractions of Shewanella
      oneidensis grown under aerobic and anaerobic conditions.
AB  - The effect of iron substrates and growth conditions on in vitro dissimilatory
      iron reduction by membrane fractions of Shewanella oneidensis MR-1 was
      characterized. Membrane fractions were separated by sucrose density gradients
      from cultures grown with O(2), fumarate, and aqueous ferric citrate as the
      terminal electron acceptor. Marker enzyme assays and two-dimensional gel
      electrophoresis demonstrated the high degree of separation between the outer and
      cytosolic membrane. Protein expression pattern was similar between chelated iron-
      and fumarate-grown cultures, but dissimilar for oxygen-grown cultures. Formate
      dependent ferric reductase activity was assayed with citrate-Fe(3+), ferrozine
      Fe(3+), and insoluble goethite as electron acceptors. No activity was detected in
      aerobic cultures. For fumarate and chelated iron-grown cells, the specific
      activity for the reduction of soluble iron was highest in the cytosolic membrane.
      The reduction of ferrozine-Fe(3+) was greater than the reduction of citrate
      Fe(3+). With goethite, the specific activity was highest in the total membrane
      fraction (containing both cytosolic and outer membrane), indicating participation
      of the outer membrane components in electron flow. Heme protein content and
      specific activity for iron reduction was highest with chelated iron-grown
      cultures with no heme proteins in aerobically grown membrane fractions. Western
      blots showed that CymA, a heme protein involved in iron reduction, expression was
      also higher in iron-grown cultures compared to fumarate- or aerobic-grown
      cultures. To study these processes, it is important to use cultures grown with
      chelated Fe(3+) as the electron acceptor and to assay ferric reductase activity
      using goethite as the substrate.

PMID- 16598000
TI  - Shear stress, temperature, and inoculation concentration influence the adhesion
      of water-stressed Helicobacter pylori to stainless steel 304 and polypropylene.
AB  - Although molecular techniques have identified Helicobacter pylori in drinking
      water-associated biofilms, there is a lack of studies reporting what factors
      affect the attachment of the bacterium to plumbing materials. Therefore, the
      adhesion of H. pylori suspended in distilled water to stainless steel 304 (SS304)
      coupons placed on tissue culture plates subjected to different environmental
      conditions was monitored. The extent of adhesion was evaluated for different
      water exposure times, using epifluorescence microscopy to count total cell
      numbers. High shear stresses-estimated through computational fluid dynamics
      negatively influenced the adhesion of H. pylori to the substrata (P < 0.001), a
      result that was confirmed in similar experiments with polypropylene (P < 0.05).
      However, the temperature and inoculation concentration appeared to have no effect
      on adhesion (P > 0.05). After 2 hours, H. pylori cells appeared to be isolated on
      the surface of SS304 and were able to form small aggregates with longer exposure
      times. However, the formation of a three-dimensional structure was only very
      rarely observed. This study suggests that the detection of the pathogen in well
      water described by other authors can be related to the increased ability of H.
      pylori to integrate into biofilms under conditions of low shear stress. It will
      also allow a more rational selection of locations to perform molecular or plate
      culture analysis for the detection of H. pylori in drinking water-associated
      biofilms.

PMID- 16598001
TI  - Methanosarcina spp. drive vinyl chloride dechlorination via interspecies hydrogen
      transfer.
AB  - Two highly enriched cultures containing Dehalococcoides spp. were used to study
      the effect of aceticlastic methanogens on reductive vinyl chloride (VC)
      dechlorination. In terms of aceticlastic methanogens, one culture was dominated
      by Methanosaeta, while the other culture was dominated by Methanosarcina, as
      determined by fluorescence in situ hybridization. Cultures amended with 2
      bromoethanesulfonate (BES), an efficient inhibitor of methanogens, exhibited slow
      VC dechlorination when grown on acetate and VC. Methanogenic cultures dominated
      by Methanosaeta had no impact on dechlorination rates, compared to BES-amended
      controls. In contrast, methanogenic cultures dominated by Methanosarcina
      displayed up to sevenfold-higher rates of VC dechlorination than their BES
      amended counterparts. Methanosarcina-dominated cultures converted a higher
      percentage of [2-(14)C]acetate to (14)CO(2) when concomitant VC dechlorination
      took place, compared to nondechlorinating controls. Respiratory indices increased
      from 0.12 in nondechlorinating cultures to 0.51 in actively dechlorinating
      cultures. During VC dechlorination, aqueous hydrogen (H(2)) concentrations
      dropped to 0.3 to 0.5 nM. However, upon complete VC consumption, H(2) levels
      increased by a factor of 10 to 100, indicating active hydrogen production from
      acetate oxidation. This process was thermodynamically favorable by means of the
      extremely low H(2) levels during dechlorination. VC degradation in
      nonmethanogenic cultures was not inhibited by BES but was limited by the
      availability of H(2) as electron donor, in cultures both with and without BES.
      These findings all indicate that Methanosarcina (but not Methanosaeta), while
      cleaving acetate to methane, simultaneously oxidizes acetate to CO(2) plus H(2),
      driving hydrogenotrophic dehalorespiration of VC to ethene by Dehalococcoides.

PMID- 16598002
TI  - A new C-type lectin similar to the human immunoreceptor DC-SIGN mediates symbiont
      acquisition by a marine nematode.
AB  - Although thiotrophic symbioses have been intensively studied for the last three
      decades, nothing is known about the molecular mechanisms of symbiont acquisition.
      We used the symbiosis between the marine nematode Laxus oneistus and sulfur
      oxidizing bacteria to study this process. In this association a monolayer of
      symbionts covers the whole cuticle of the nematode, except its anterior-most
      region. Here, we identify a novel Ca(2+)-dependent mannose-specific lectin that
      was exclusively secreted onto the posterior, bacterium-associated region of L.
      oneistus cuticle. A recombinant form of this lectin induced symbiont aggregation
      in seawater and was able to compete with the native lectin for symbiont binding
      in vivo. Surprisingly, the carbohydrate recognition domain of this mannose
      binding protein was similar both structurally and functionally to a human
      dendritic cell-specific immunoreceptor. Our results provide a molecular link
      between bacterial symbionts and host-secreted mucus in a marine symbiosis and
      suggest conservation in the mechanisms of host-microbe interactions throughout
      the animal kingdom.

PMID- 16598003
TI  - Protein kinase C (PkcA) of Aspergillus nidulans is involved in penicillin
      production.
AB  - The biosynthesis of the beta-lactam antibiotic penicillin in the filamentous
      fungus Aspergillus nidulans is catalyzed by three enzymes that are encoded by the
      acvA, ipnA, and aatA genes. A variety of cis-acting DNA elements and regulatory
      factors form a complex regulatory network controlling these beta-lactam
      biosynthesis genes. Regulators involved include the CCAAT-binding complex AnCF
      and AnBH1. AnBH1 acts as a repressor of the penicillin biosynthesis gene aatA.
      Until now, however, little information has been available on the signal
      transduction cascades leading to the transcription factors. Here we show that
      inhibition of protein kinase C (Pkc) activity in A. nidulans led to cytoplasmic
      localization of an AnBH1-enhanced green fluorescent protein (EGFP) fusion
      protein. Computer analysis of the genome and screening of an A. nidulans gene
      library revealed that the fungus possesses two putative Pkc-encoding genes, which
      we designated pkcA and pkcB. Only PkcA showed all the characteristic features of
      fungal Pkc's. Production of pkcA antisense RNA in A. nidulans led to reduced
      growth and conidiation in Aspergillus minimal medium, while in fermentation
      medium it led to enhanced expression of an aatAp-lacZ gene fusion, reduced
      pencillin production, and predominantly cytoplasmic localization of AnBH1. These
      data agree with the finding that inhibition of Pkc activity prevented nuclear
      localization of AnBH1-EGFP. As a result, repression of aatA expression was
      relieved. The involvement of Pkc in penicillin biosynthesis is also interesting
      in light of the fact that in the yeast Saccharomyces cerevisiae, Pkc plays a
      major role in maintaining cell integrity.

PMID- 16598004
TI  - Succession and regulation factors of small eukaryote community composition in a
      lacustrine ecosystem (Lake Pavin).
AB  - The structure and dynamics of small eukaryotes (cells with a diameter less than 5
      microm) were studied over two consecutive years in an oligomesotrophic lake (Lake
      Pavin in France). Water samples were collected at 5 and 30 m below the surface;
      when the lake was stratified, these depths corresponded to the epilimnion and
      hypolimnion. Changes in small-eukaryote structure were analyzed using terminal
      restriction fragment length polymorphism (T-RFLP) and cloning and sequencing of
      the 18S rRNA genes. Terminal restriction fragments from clones were used to
      reveal the dominant taxa in T-RFLP profiles of the environmental samples.
      Spumella-like cells (Chrysophyceae) did not dominate the small eukaryote
      community identified by molecular techniques in lacustrine ecosystems. Small
      eukaryotes appeared to be dominated by heterotrophic cells, particularly
      Cercozoa, which represented nearly half of the identified phylotypes, followed by
      the Fungi-LKM11 group (25%), choanoflagellates (10.3%) and Chrysophyceae (8.9%).
      Bicosoecida, Cryptophyta, and ciliates represented less than 9% of the community
      studied. No seasonal reproducibility in temporal evolution of the small-eukaryote
      community was observed from 1 year to the next. The T-RFLP patterns were related
      to bottom-up (resources) and top-down (grazing) variables using canonical
      correspondence analysis. The results showed a strong top-down regulation of small
      eukaryotes by zooplankton, more exactly, by cladocerans at 5 m and copepods at 30
      m. Among bottom-up factors, temperature had a significant effect at both depths.
      The concentrations of nitrogenous nutrients and total phosphorus also had an
      effect on small-eukaryote dynamics at 5 m, whereas bacterial abundance and
      dissolved oxygen played a more important structuring role in the deeper zone.

PMID- 16598005
TI  - Acanthocytes of Stropharia rugosoannulata function as a nematode-attacking
      device.
AB  - Efficient killing of nematodes by Stropharia rugosoannulata Farlow ex Murrill
      cultures was observed. This fungus showed the ability to immobilize the free
      living nematode Panagrellus redivivus Goodey within minutes and to immobilize the
      pine wilt nematode Bursaphelenchus xylophilus (Steiner & Buhrer) Nickle within
      hours on agar plates. Moreover, P. redivivus worms were completely degraded by
      the fungus within 24 to 48 h. The cultures of S. rugosoannulata studied shared
      the characteristic of abundantly producing cells with finger-like projections
      called acanthocytes. We showed that the nematode-attacking activity of this
      fungus is carried out by these spiny acanthocytes and that mechanical force is an
      important factor in the process. Furthermore, the growth and nematode-attacking
      activity of the fungus in soil were also determined, and our results suggest that
      acanthocytes are functional in soil.

PMID- 16598006
TI  - Peptidoglycan hydrolase fusions maintain their parental specificities.
AB  - The increased incidence of bacterial antibiotic resistance has led to a renewed
      search for novel antimicrobials. Avoiding the use of broad-range antimicrobials
      through the use of specific peptidoglycan hydrolases (endolysins) might reduce
      the incidence of antibiotic-resistant pathogens worldwide. Staphylococcus aureus
      and Streptococcus agalactiae are human pathogens and also cause mastitis in dairy
      cattle. The ultimate goal of this work is to create transgenic cattle that are
      resistant to mastitis through the expression of an antimicrobial protein(s) in
      their milk. Toward this end, two novel antimicrobials were produced. The (i) full
      length and (ii) 182-amino-acid, C-terminally truncated S. agalactiae
      bacteriophage B30 endolysins were fused to the mature lysostaphin protein of
      Staphylococcus simulans. Both fusions display lytic specificity for streptococcal
      pathogens and S. aureus. The full lytic ability of the truncated B30 protein also
      suggests that the SH3b domain at the C terminus is dispensable. The fusions are
      active in a milk-like environment. They are also active against some lactic acid
      bacteria used to make cheese and yogurt, but their lytic activity is destroyed by
      pasteurization (63 degrees C for 30 min). Immunohistochemical studies indicated
      that the fusion proteins can be expressed in cultured mammalian cells with no
      obvious deleterious effects on the cells, making it a strong candidate for use in
      future transgenic mice and cattle. Since the fusion peptidoglycan hydrolase also
      kills multiple human pathogens, it also may prove useful as a highly selective,
      multipathogen-targeting antimicrobial agent that could potentially reduce the use
      of broad-range antibiotics in fighting clinical infections.

PMID- 16598007
TI  - Isolation, pure culture, and characterization of "Candidatus Arsenophonus
      arthropodicus," an intracellular secondary endosymbiont from the hippoboscid
      louse fly Pseudolynchia canariensis.
AB  - Members of the genus Arsenophonus comprise a large group of bacterial
      endosymbionts that are widely distributed in arthropods of medical, veterinary,
      and agricultural importance. At present, little is known about the role of these
      bacteria in arthropods, because few representatives have been isolated and
      cultured in the laboratory. In the current study, we describe the isolation and
      pure culture of an Arsenophonus endosymbiont from the hippoboscid louse fly
      Pseudolynchia canariensis. We propose provisional nomenclature for this bacterium
      in the genus Arsenophonus as "Candidatus Arsenophonus arthropodicus."
      Phylogenetic analyses indicate that "Candidatus Arsenophonus arthropodicus" is
      closely related to the Arsenophonus endosymbionts found in psyllids, whiteflies,
      aphids, and mealybugs. The pure culture of this endosymbiont offers new
      opportunities to examine the role of Arsenophonus in insects. To this end, we
      describe methods for the culture of "Candidatus Arsenophonus arthropodicus" in an
      insect cell line and the transformation of this bacterium with a broad-host-range
      plasmid.

PMID- 16598009
TI  - Culture conditions of Roseobacter strain 27-4 affect its attachment and biofilm
      formation as quantified by real-time PCR.
AB  - The fish probiotic bacterium Roseobacter strain 27-4 grows only as rosettes and
      produces its antibacterial compound under static growth conditions. It forms
      three-dimensional biofilms when precultured under static conditions. We
      quantified attachment of Roseobacter strain 27-4 using a direct real-time PCR
      method and demonstrated that the bacteria attached more efficiently to surfaces
      during static growth than under aerated conditions.

PMID- 16598008
TI  - Elevated shear stress protects Escherichia coli cells adhering to surfaces via
      catch bonds from detachment by soluble inhibitors.
AB  - Soluble inhibitors find widespread applications as therapeutic drugs to reduce
      the ability of eukaryotic cells, bacteria, or viruses to adhere to surfaces and
      host tissues. Mechanical forces resulting from fluid flow are often present under
      in vivo conditions, and it is commonly presumed that fluid flow will further add
      to the inhibitive effect seen under static conditions. In striking contrast, we
      discover that when surface adhesion is mediated by catch bonds, whose bond life
      increases with increased applied force, shear stress may dramatically increase
      the ability of bacteria to withstand detachment by soluble competitive
      inhibitors. This shear stress-induced protection against inhibitor-mediated
      detachment is shown here for the fimbrial FimH-mannose-mediated surface adhesion
      of Escherichia coli. Shear stress-enhanced reduction of bacterial detachment has
      major physiological and therapeutic implications and needs to be considered when
      developing and screening drugs.

PMID- 16598011
TI  - Analysis of the thermostability determinants of hyperthermophilic esterase EstE1
      based on its predicted three-dimensional structure.
AB  - The three-dimensional (3D) structure of the hyperthermophilic esterase EstE1 was
      constructed by homology modeling using Archaeoglobus fulgidus esterase as a
      reference, and the thermostability-structure relationship was analyzed. Our
      results verified the predicted 3D structure of EstE1 and identified the ion pair
      networks and hydrophobic interactions that are critical determinants for the
      thermostability of EstE1.

PMID- 16598010
TI  - Fluorescence in situ hybridization and spectral imaging of coral-associated
      bacterial communities.
AB  - Microbial communities play important roles in the functioning of coral reef
      communities. However, extensive autofluorescence of coral tissues and
      endosymbionts limits the application of standard fluorescence in situ
      hybridization (FISH) techniques for the identification of the coral-associated
      bacterial communities. This study overcomes these limitations by combining FISH
      and spectral imaging.

PMID- 16598012
TI  - Does green light influence the fluorescence properties and structure of
      phototrophic biofilms?
AB  - Artificial illumination can harm works of art by inducing the development of
      photosynthetic biofilms. With the aim of preventing biodeterioration or esthetic
      damage to such surfaces, we evaluated and compared the effects of illuminating
      biofilms formed by Gloeothece membranacea (cyanobacteria) and Chlorella
      sorokiniana (Chlorophyta) using exclusively white or green light.

PMID- 16598013
TI  - Laboratory-dependent bacterial ecology: a cautionary tale.
AB  - Although laboratory dependence is an acknowledged problem in microbiology, it is
      seldom intensively studied or discussed. We demonstrate that laboratory
      dependence is real and quantifiable even in the popular model Escherichia coli.
      Here laboratory effects alter the equilibrium composition of a simple community
      composed of two strains of E. coli. Our data rule out changes in the bacterial
      strains, chemical batches, and human handling but implicate differences in growth
      medium, especially the water component.

PMID- 16598014
TI  - Characterization of Streptococcus thermophilus host range phage mutants.
AB  - To investigate phage-host interactions in Streptococcus thermophilus, a phage
      resistant derivative (SMQ-301R) was obtained by challenging a Tn917 library of
      phage-sensitive strain S. thermophilus SMQ-301 with virulent phage DT1. Mutants
      of phages DT1 and MD2 capable of infecting SMQ-301 and SMQ-301R were isolated at
      a frequency of 10(-6). Four host range phage mutants were analyzed further and
      compared to the two wild-type phages. Altogether, three genes (orf15, orf17, and
      orf18) contained point mutations leading to amino acid substitutions and were
      responsible for the expanded host range. These three proteins were also
      identified in both phages by N-terminal sequencing and/or matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry. The results suggest that
      at least three phage structural proteins may be involved in phage-host
      interactions in S. thermophilus.

PMID- 16598015
TI  - In vitro and in vivo survival and transit tolerance of potentially probiotic
      strains carried by artichokes in the gastrointestinal tract.
AB  - The ability of potentially probiotic strains of Lactobacillus plantarum and
      Lactobacillus paracasei to survive on artichokes for at least 90 days was shown.
      The anchorage of bacterial strains to artichokes improved their survival in
      simulated gastrointestinal digestion. L. paracasei IMPC2.1 was further used in an
      artichoke human feeding study involving four volunteers, and it was shown that
      the organism could be recovered from stools.

PMID- 16598016
TI  - Antimicrobial susceptibility and characterization of Salmonella isolates from
      processed bison carcasses.
AB  - Seventeen Salmonella enterica serovar Hadar isolates recovered from bison were
      found to possess a range of virulence genes and resistance to tetracycline,
      gentamicin, sulfamethoxazole, and streptomycin simultaneously. A 1-kb class 1
      integron containing the aadA1 gene was identified in all isolates. Pulsed-field
      gel electrophoresis found that all isolates were closely related, indicating the
      possibility of cross-contamination during processing.

PMID- 16598017
TI  - Safety assessment of the oral cavity probiotic Streptococcus salivarius K12.
AB  - Streptococcus salivarius is a prominent member of the oral microbiota and has
      excellent potential for use as a probiotic targeting the oral cavity. In this
      report we document safety data relating to S. salivarius K12, including
      assessment of its antibiogram, metabolic profiles, and virulence determinants,
      and we examine the microbial composition of saliva following the dosing of
      subjects with K12.

PMID- 16598018
TI  - SXT-related integrating conjugative element in New World Vibrio cholerae.
AB  - SXT-related integrating conjugative elements (ICEs) became prevalent in Asian
      Vibrio cholerae populations after V. cholerae O139 emerged. Here, we describe an
      SXT-related ICE, ICEVchMex1, in a Mexican environmental V. cholerae isolate.
      Identification of ICEVchMex1 represents the first description of an SXT-related
      ICE in the Western Hemisphere. The significant differences between the SXT and
      ICEVchMex1 genomes suggest that these ICEs have evolved independently.

PMID- 16598020
TI  - Produce isolates of the Escherichia coli Ont:H52 serotype that carry both Shiga
      toxin 1 and stable toxin genes.
AB  - Produce isolates of the Escherichia coli Ont:H52 serotype carried Shiga toxin 1
      and stable toxin genes but only expressed Stx1. These strains had pulsed-field
      gel electrophoresis profiles that were 90% homologous to clinical Ont:H52 strains
      that had identical phenotypes and genotypes. All Ont:H52 strains had identical
      single nucleotide polymorphism profiles that are suggestive of a unique clonal
      group.

PMID- 16598019
TI  - Occurrence of Vibrio parahaemolyticus, V. cholerae, and V. vulnificus in
      Norwegian Blue Mussels (Mytilus edulis).
AB  - Vibrio parahaemolyticus, V. cholerae, and V. vulnificus were isolated from 10.3%,
      1.0%, and 0.1% of 885 blue mussel samples, respectively. Four of the samples
      contained trh(+) V. parahaemolyticus, while no tdh-positive isolates were
      detected. The V. cholerae isolates were non-O:1/non-O:139 serotypes and were ctxA
      negative.

PMID- 16598021
TI  - PslD is a secreted protein required for biofilm formation by Pseudomonas
      aeruginosa.
AB  - The function of pslD, which is part of the psl operon from Pseudomonas
      aeruginosa, was investigated in this study. The psl operon is involved in
      exopolysaccharide biosynthesis and biofilm formation. An isogenic marker-free
      pslD deletion mutant of P. aeruginosa PAO1 which was deficient in the formation
      of differentiated biofilms was generated. Expression of only the pslD gene coding
      region restored the wild-type phenotype. A C-terminal, hexahistidine tag fusion
      enabled the identification of PslD. LacZ and PhoA translational fusions with PslD
      indicated that PslD is a secreted protein required for biofilm formation,
      presumably via its role in exopolysaccharide export.

PMID- 16598022
TI  - Arsenic resistance in Campylobacter spp. isolated from retail poultry products.
AB  - Organoarsenicals are commonly used for growth promotion in U.S. poultry
      production. Susceptibilities to arsenite, arsenate, and the organoarsenical
      roxarsone were measured in 251 Campylobacter isolates from conventional and
      antimicrobial-free retail poultry products. Isolates from conventional poultry
      products had significantly higher roxarsone MICs (z = 8.22; P < 0.0001).

PMID- 16598023
TI  - Absence of VanA- and VanB-containing enterococci in poultry raised on
      nonintensive production farms in Brazil.
AB  - We examined cloacal samples from poultry raised on nonintensive production farms
      in Brazil for the presence of vancomycin-resistant enterococci. No VanA- or VanB
      containing enterococci were identified in a total of 200 cloacal swabs. The most
      prevalent species were Enterococcus gallinarum (vanC1; 13.0%) and E.
      casseliflavus (vanC2/3; 5.5%).

PMID- 16598024
TI  - Prevalence of Borrelia burgdorferi sensu lato and Anaplasmataceae members in
      Ixodes ricinus ticks in Alsace, a focus of Lyme borreliosis endemicity in France.
AB  - Due to the high Lyme borreliosis incidence in Alsace, in northeastern France, we
      investigated in 2003-2004 three cantons in this region in order to determine the
      density of Ixodes ricinus ticks infected by Borrelia burgdorferi sensu lato and
      Anaplasmataceae. The peak density of nymphs infected by B. burgdorferi sensu lato
      at Munster and Guebwiller, where the disease incidence was high, was among the
      highest reported in Europe (105 and 114 per 100 m(2), respectively). In contrast,
      the peak density of infected nymphs was low in the canton of Dannemarie (5/100
      m(2)), where the disease incidence was low. The two main species detected in
      ticks were Borrelia afzelii, more frequent in nymphs, and Borrelia garinii, more
      frequent in adult ticks. The rates of tick infection by Anaplasma phagocytophilum
      were 0.4% and 1.2% in nymphs and adults, respectively.

PMID- 16598026
TI  - Clonal origin of germ cell colonies after spermatogonial transplantation in mice.
AB  - Spermatogenesis originates from a small number of spermatogonial stem cells that
      can reinitiate spermatogenesis and produce germ cell colonies following
      transplantation into infertile recipient testes. Although several previous
      studies have suggested a single-cell origin of germ cell colonies, only indirect
      evidence has been presented. In this investigation, we tested the clonal origin
      hypothesis using a retrovirus, which could specifically mark an individual
      spermatogonial stem cell. Spermatogonial stem cells were infected in vitro with
      an enhanced green fluorescence protein-expressing retrovirus and subsequently
      transplanted into infertile recipient mice. Live haploid germ cells were
      recovered from individual colonies and were microinjected into eggs to create
      offspring. In total, 45 offspring were produced from five colonies, and 23 (51%)
      of the offspring were transgenic. Southern blot analysis indicated that the
      transgenic offspring from the single colony carried a common integration site,
      and the integration site was different among the transgenic offspring from
      different colonies. These results provide evidence that germ cell colonies
      develop from single spermatogonial stem cells.

PMID- 16598025
TI  - Diversity and distribution of Planctomycetes and related bacteria in the suboxic
      zone of the Black Sea.
AB  - Samples from six depths of the Black Sea's suboxic zone were analyzed for 16S
      rRNA gene sequence information. A gradient in phylotype diversity was found. The
      distributions of known anaerobic ammonium oxidation (anammox) bacteria, many
      unknown Planctomycetes, and other phylotypes were examined in relation to the
      local nutrient and redox conditions.

PMID- 16598027
TI  - Demonstration of follicle-stimulating hormone receptor in cauda epididymis of
      rat.
AB  - FSH receptor has been shown to be specifically expressed only in the Sertoli
      cells in males. In one of our studies that consisted of deprival of endogenous
      FSH in immature rats and adult bonnet monkeys, atrophy of the epididymis was
      observed, cauda region being the most affected. Although epididymis is an
      androgen-dependent tissue, the changes in histology of the cauda region were
      observed without any associated change in the levels of testosterone in FSH
      deprived animals. Considering this, it was of interest to evaluate the
      possibility of epididymis being a direct target for FSH action. In the present
      study, we have examined the expression of FSH receptor in the epididymis of rat
      and monkey. In the cauda region of rat epididymis, FSH receptor expression was
      demonstrated by RT-PCR and Northern and Western blot analyses. FSH receptor was
      found to be functional as observed by its ability to bind 125IoFSH, by an
      increase in cAMP production, and by BrdU incorporation following addition of FSH
      under in vitro conditions. These results suggest the possibility of a role for
      FSH in regulating the growth of the epididymis.

PMID- 16598028
TI  - Azoospermia: virtual reality or possible to quantify?

PMID- 16598029
TI  - Varicocele and fertility: relationship between testicular volume and seminal
      parameters before and after treatment.
AB  - Varicocele is a condition of varicosity and tortuosity of the pampiniform plexus
      that is often associated with a reduction in the volume of the affected testicle.
      Today there is much debate about how much the varicocele actually damages the
      reproductive system and the mechanism through which this occurs. Furthermore, it
      has not yet clearly been established if treatment is truly useful to restore
      testicular function. The goal of this study was to evaluate changes in the volume
      of the affected testis after treatment and to examine any correlations between
      volume and seminal parameters. We evaluated 43 patients with left idiopathic
      varicocele with ultrasound scan of the testis before and after surgery;
      testicular volume was obtained using the ellipsoid formula. We also examined
      semen parameters before and at an average time of 1 year after the procedure,
      using the WHO indications. We performed 2 statistical analyses, comparing changes
      in testicular volume before and after surgery, and volume with seminal
      parameters. Statistical analysis shows a significant increase of testicular
      volume after varicocele treatment (P < .05). Furthermore, the total number of
      spermatozoa and fast progressive spermatozoa rates significantly increased after
      surgery (respectively P < .05 and P < .01) (Figure 1). The Spearman correlation
      coefficient shows a good relationship between testicular volume and total number
      of spermatozoa (r = .445; P = .01). Our data point to the possibility that the
      affected testicle could benefit in terms of trophism and function after
      varicocele treatment. Ultrasound scan at follow-up permits assessment of not only
      the presence of recurrence, but it is also useful for evaluating trophism.

PMID- 16598030
TI  - Hotchkiss and MacLeod: an historical perspective.

PMID- 16598031
TI  - The length of the spermatogenic cycle is conserved in porcine and ovine testis
      xenografts.
AB  - Xenografting of immature mammalian testis tissue into mice can accelerate sperm
      production. To determine whether this shortened time to sperm production is
      because of reduced length of the spermatogenic cycle, we applied
      bromodeoxyuridine (BrdU) incorporation to analyze the spermatogenic cycle in
      porcine and ovine testis xenografts. Small testis fragments from newborn pigs and
      sheep were ectopically grafted into mice. Once complete spermatogenesis was
      present in grafted tissue, mice were injected with BrdU and grafts were recovered
      at different time points thereafter. In porcine grafts, the most advanced germ
      cells labeled 1 hour, 9 days, 12.3 days, and 18 days after BrdU injection were
      stage 1 preleptotene/leptotene primary spermatocytes, stage 1 pachytene primary
      spermatocytes, stage 5 newly-formed round spermatids, and late stage 2 elongating
      spermatids, respectively. In ovine grafts, the most advanced labeled germ cells
      at 1 hour, 11 days, and 22 days post-BrdU injection were stage 2
      preleptotene/leptotene primary spermatocytes, late stage 1 pachytene primary
      spermatocytes, and stage 2 elongating spermatids, respectively. These results
      indicate that each spermatogenic cycle in porcine and ovine xenografts lasts
      approximately 9 and 11 days, respectively, which is similar to their durations in
      situ. Therefore, the length of the spermatogenic cycle is conserved in porcine
      and ovine testis xenografts. This is consistent with earlier reports showing that
      the cycle length is inherent to the germ cell genotype. The shortened time to
      sperm production in xenografts therefore appears attributable to accelerated
      maturation of the testicular somatic compartments. Our results suggest that
      testis xenografts provide a useful model to study the timing of testicular
      maturation and spermatogenesis in different mammalian species.

PMID- 16598032
TI  - Treatment strategy for locally recurrent rectal cancer.
AB  - Despite radical surgery, up to 33% of patients with rectal cancer will develop
      locoregional relapse. The management of these patients is particularly
      challenging. Surgery is the mainstay of treatment for those with a mobile
      recurrence. However, the majority of patients develop recurrence involving the
      pelvic wall. In these patients, multimodality therapy including radical surgery
      and intraoperative radiotherapy have been reported with 5-year survival of up to
      31% and local control rates of 50-71%. The most important factor for obtaining
      long-term local control and survival is R0 resection. Extended surgery such as
      abdomino-sacral resection has not been popular because of 5-year survival rates
      of 16-31%, and significant postoperative morbidity. Re-recurrence following
      surgery occurs locally and in the lung, and remains a significant problem. In
      surgical treatment for local recurrence, surgeon-related factors are crucial. A
      staging system using degree of fixation and other prognostic factors should be
      developed so that appropriate treatment modalities are applied to each case.

PMID- 16598034
TI  - International comparisons of cumulative risk of colorectal cancer, from cancer
      incidence in five continents vol. VIII.

PMID- 16598033
TI  - A case of T1 sigmoid colon cancer with lymph node involvement.

PMID- 16598035
TI  - G-banded karyotype and ideogram for the North Atlantic right whale (Eubalaena
      glacialis).
AB  - Published cytogenetic data for extant cetacean species remain incomplete. In a
      review of the literature, we found karyotypic information for 6 of the 13
      tentatively recognized species of the suborder Mysticeti (baleen whales). Among
      those yet to be described is the critically endangered North Atlantic right whale
      (Eubalaena glacialis). Herein, we describe and propose a first-generation G
      banded karyotype and ideogram for this species (2n = 42), obtained from
      peripheral blood chromosome preparations from a stranded male calf. This
      information may prove useful for future genetic mapping projects and for
      interspecific and intraspecific genomic comparisons by techniques such as zoo
      FISH.

PMID- 16598036
TI  - Genetic divergence of Connecticut Melanoplus femurrubrum populations.
AB  - We surveyed Melanoplus femurrubrum populations within the state of Connecticut
      for genetic diversity at multiple genetic markers, including three mitochondrial
      [cytochrome oxidase subunit 1 (COI), reduced form of nicotinamide adenine
      dinucleotide dehydrogenase subunit 2 (ND2), and AT rich] and one nuclear
      [internal transcribed spacers of the ribosomal DNA cluster (ITS1)] gene regions.
      All markers were variable, and the AT-rich gene showed the highest sequence
      divergence. Analysis of molecular variance (AMOVA), fixation index (Fst)
      analysis, and phylogeographic patterns showed little divergence between northern
      and southern regions. Estimates of genetic diversity (pi) showed higher
      mitochondrial diversity in the northern region but nearly equal diversity for the
      ITS1 gene. This study shows for the first time in Melanoplus genetic variation
      for the ND2, AT rich, and ITS genes within a small geographic area. Our methods
      and results should be useful for other researchers interested in conducting
      population-level studies on closely related species.

PMID- 16598037
TI  - Derepression of the Her-2 uORF is mediated by a novel post-transcriptional
      control mechanism in cancer cells.
AB  - Transcripts harboring 5' upstream open reading frames (uORFs) are often found in
      genes controlling cell growth including receptors, oncogenes, or growth factors.
      uORFs can modulate translation or RNA stability and mediate inefficient
      translation of these potent proteins under normal conditions. In dysregulated
      cancer cells, where the gene product, for example Her-2 receptor, is
      overexpressed, post-transcriptional processes must exist that serve to override
      the inhibitory effects of the uORFs. The 5' untranslated region (UTR) of Her-2
      mRNA contains a short uORF that represses translation of the downstream coding
      region. We demonstrate that in Her-2 overexpressing breast cancer cells, the 3'
      UTR of the Her-2 mRNA can override translational inhibition mediated by the Her-2
      uORF. Within this 3' UTR, a translational derepression element (TDE) that binds
      to a 38-kDa protein was identified. These results define a novel biological
      mechanism in which translational control of genes harboring a 5' uORF can be
      modulated by elements in their 3' UTRs.

PMID- 16598038
TI  - The Drosophila P68 RNA helicase regulates transcriptional deactivation by
      promoting RNA release from chromatin.
AB  - Terminating a gene's activity requires that pre-existing transcripts be matured
      or destroyed and that the local chromatin structure be returned to an inactive
      configuration. Here we show that the Drosophila homolog of the mammalian P68 RNA
      helicase plays a novel role in RNA export and gene deactivation. p68 mutations
      phenotypically resemble mutations in small bristles (sbr), the Drosophila homolog
      of the human mRNA export factor NXF1. Full-length hsp70 mRNA accumulates in the
      nucleus near its sites of transcription following heat shock of p68 homozygotes,
      and hsp70 gene shutdown is delayed. Unstressed mutant larvae show similar defects
      in transcript accumulation and gene repression at diverse loci, and we find that
      p68 mutations are allelic to Lighten-up, a known suppressor of position effect
      variegation. Our observations reveal a strong connection between transcript
      clearance and gene repression. P68 may be needed to rapidly remove transcripts
      from a gene before its activity can be shut down and its chromatin reset to an
      inactive state.

PMID- 16598039
TI  - Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows
      dynamic interplay with positive-acting histone modifications.
AB  - Covalent histone post-translational modifications such as acetylation,
      methylation, phosphorylation, and ubiquitylation play pivotal roles in regulating
      many cellular processes, including transcription, response to DNA damage, and
      epigenetic control. Although positive-acting post-translational modifications
      have been studied in Saccharomyces cerevisiae, histone modifications that are
      associated with transcriptional repression have not been shown to occur in this
      yeast. Here, we provide evidence that histone sumoylation negatively regulates
      transcription in S. cerevisiae. We show that all four core histones are
      sumoylated and identify specific sites of sumoylation in histones H2A, H2B, and
      H4. We demonstrate that histone sumoylation sites are involved directly in
      transcriptional repression. Further, while histone sumoylation occurs at all loci
      tested throughout the genome, slightly higher levels occur proximal to telomeres.
      We observe a dynamic interplay between histone sumoylation and either acetylation
      or ubiquitylation, where sumoylation serves as a potential block to these
      activating modifications. These results indicate that sumoylation is the first
      negative histone modification to be identified in S. cerevisiae and further
      suggest that sumoylation may serve as a general dynamic mark to oppose
      transcription.

PMID- 16598040
TI  - Phosphorylation of NtMAP65-1 by a MAP kinase down-regulates its activity of
      microtubule bundling and stimulates progression of cytokinesis of tobacco cells.
AB  - The tobacco mitogen-activated protein kinase (MAPK) cascade, which includes MAPK
      NRK1/NTF6, positively regulates expansion of the cytokinetic machinery known as
      the phragmoplast, which is followed by the synthesis of cell plates for
      completion of cell division. However, molecular events lying between the MAPK and
      phragmoplast expansion were not known. Here, we show that NRK1/NTF6
      phosphorylates the threonine residue at position 579 in NtMAP65-1a, a microtubule
      associated (MT-associated) protein. Levels of phosphorylated NtMAP65-1 increase
      during late M phase of the cell cycle, when NRK1/NTF6 is activated.
      Phosphorylated NtMAP65-1 is concentrated at the equator of phragmoplast, as is
      NRK1/NTF6. Overexpression of mutant forms of NtMAP65-1a that cannot be
      phosphorylated by NRK1 delays progression of the M phase and phragmoplast
      expansion, also rendering phragmoplast structures resistant to an MT
      depolymerizing drug. Phosphorylation of NtMAP65-1 by NRK1/NTF6 down-regulates its
      MT-bundling activity in vitro. These results suggest that phosphorylation of
      NtMAP65-1 by NRK1/NTF6 also reduces its MT-bundling activity in vivo, which
      enhances destabilization and turnover of MTs at the phragmoplast equator, perhaps
      facilitating phragmoplast expansion.

PMID- 16598042
TI  - The changing face of teenage drug abuse--the trend toward prescription drugs.

PMID- 16598041
TI  - The role of Rat1 in coupling mRNA 3'-end processing to transcription termination:
      implications for a unified allosteric-torpedo model.
AB  - The torpedo model of transcription termination by RNA polymerase II proposes that
      a 5'-3' RNA exonuclease enters at the poly(A) cleavage site, degrades the nascent
      RNA, and eventually displaces polymerase from the DNA. Cotranscriptional
      degradation of nascent RNA has not been directly demonstrated, however. Here we
      report that two exonucleases, Rat1 and Xrn1, both contribute to cotranscriptional
      degradation of nascent RNA, but this degradation is not sufficient to cause
      polymerase release. Unexpectedly, Rat1 functions in both 3'-end processing and
      termination by enhancing recruitment of 3'-end processing factors, including
      Pcf11 and Rna15. In addition, the cleavage factor Pcf11 reciprocally aids in
      recruitment of Rat1 to the elongation complex. Our results suggest a unified
      allosteric/torpedo model in which Rat1 is not a dedicated termination factor, but
      is an integrated component of the cleavage/polyadenylation apparatus.

PMID- 16598043
TI  - Small vessels, big problems.

PMID- 16598044
TI  - Effect of introduction of the pneumococcal conjugate vaccine on drug-resistant
      Streptococcus pneumoniae.
AB  - BACKGROUND: Five of seven serotypes in the pneumococcal conjugate vaccine,
      introduced for infants in the United States in 2000, are responsible for most
      penicillin-resistant infections. We examined the effect of this vaccine on
      invasive disease caused by resistant strains. METHODS: We used laboratory-based
      data from Active Bacterial Core surveillance to measure disease caused by
      antibiotic-nonsusceptible pneumococci from 1996 through 2004. Cases of invasive
      disease, defined as disease caused by pneumococci isolated from a normally
      sterile site, were identified in eight surveillance areas. Isolates underwent
      serotyping and susceptibility testing. RESULTS: Rates of invasive disease caused
      by penicillin-nonsusceptible strains and strains not susceptible to multiple
      antibiotics peaked in 1999 and decreased by 2004, from 6.3 to 2.7 cases per
      100,000 (a decline of 57 percent; 95 percent confidence interval, 55 to 58
      percent) and from 4.1 to 1.7 cases per 100,000 (a decline of 59 percent; 95
      percent confidence interval, 58 to 60 percent), respectively. Among children
      under two years of age, disease caused by penicillin-nonsusceptible strains
      decreased from 70.3 to 13.1 cases per 100,000 (a decline of 81 percent; 95
      percent confidence interval, 80 to 82 percent). Among persons 65 years of age or
      older, disease caused by penicillin-nonsusceptible strains decreased from 16.4 to
      8.4 cases per 100,000 (a decline of 49 percent). Rates of resistant disease
      caused by vaccine serotypes fell 87 percent. An increase was seen in disease
      caused by serotype 19A, a serotype not included in the vaccine (from 2.0 to 8.3
      per 100,000 among children under two years of age). CONCLUSIONS: The rate of
      antibiotic-resistant invasive pneumococcal infections decreased in young children
      and older persons after the introduction of the conjugate vaccine. There was an
      increase in infections caused by serotypes not included in the vaccine.

PMID- 16598045
TI  - Role of COL4A1 in small-vessel disease and hemorrhagic stroke.
AB  - Small-vessel diseases of the brain underlie 20 to 30 percent of ischemic strokes
      and a larger proportion of intracerebral hemorrhages. In this report, we show
      that a mutation in the mouse Col4a1 gene, encoding procollagen type IV alpha1,
      predisposes both newborn and adult mice to intracerebral hemorrhage. Surgical
      delivery of mutant mice alleviated birth-associated trauma and hemorrhage. We
      identified a COL4A1 mutation in a human family with small-vessel disease. We
      concluded that mutation of COL4A1 may cause a spectrum of cerebrovascular
      phenotypes and that persons with COL4A1 mutations may be predisposed to
      hemorrhage, especially after environmental stress.

PMID- 16598046
TI  - Clinical practice. Sexual desire and arousal disorders in women.

PMID- 16598047
TI  - The biology of human sex differences.

PMID- 16598048
TI  - Images in clinical medicine. A medical mystery--gangrene and cutaneous nodules.

PMID- 16598049
TI  - Clinical problem-solving. A jaundiced eye.

PMID- 16598050
TI  - Pneumococcal vaccine--direct and indirect ("herd") effects.

PMID- 16598051
TI  - Letrozole or tamoxifen in early breast cancer.

PMID- 16598052
TI  - Benazepril for advanced chronic renal insufficiency.

PMID- 16598053
TI  - Immune cells in colorectal cancer.

PMID- 16598054
TI  - Febuxostat versus allopurinol for gout.

PMID- 16598056
TI  - Cost-effectiveness of cervical-cancer screening in developing countries.

PMID- 16598055
TI  - Hirsutism.

PMID- 16598058
TI  - Repair of small abdominal aortic aneurysms.

PMID- 16598057
TI  - Living-donor liver transplantation for chronic hepatic graft-versus-host disease.

PMID- 16598059
TI  - Primary culture of gustatory receptor neurons from the blowfly, Phormia regina.
AB  - Flies provide a powerful model system for exploring signaling systems in
      gustatory receptor neurons (GRNs). To elucidate the cellular and molecular bases
      of these signaling systems, we sought to develop techniques to dissociate GRNs.
      We developed a primary culture of GRNs isolated from the labella of the blowfly,
      Phormia regina, 4-5 days after pupation. Dissected labella were treated with
      papain in a low Ca2+ saline solution and shaken in Leibovitz's L-15 medium
      supplemented with 20-hydroxyecdysone, L-ascorbic acid, and trehalose with a test
      tube mixer. Released cells were plated and kept at 29 degrees C in a medium
      containing fetal bovine serum. After a minimum of 2 days in culture, we observed
      survival or growth of bipolar cells with the characteristic morphology of GRNs.
      We also examined taste responsiveness by monitoring intracellular Ca2+ with a
      Ca2+-sensitive fluorescent dye, fluo-3. For some bipolar cells, application of
      sucrose, NaCl, or LiCl for 5-20 s transiently increased the intracellular Ca2+
      levels in cell bodies for 20-30 s. The primary cell culture described here is
      useful for functional analysis of GRNs.

PMID- 16598060
TI  - Oscillatory and intrinsic membrane properties of guinea pig nucleus prepositus
      hypoglossi neurons in vitro.
AB  - Numerous models of the oculomotor neuronal integrator located in the prepositus
      hypoglossi nucleus (PHN) involve both highly tuned recurrent networks and
      intrinsic neuronal properties; however, there is little experimental evidence for
      the relative role of these two mechanisms. The experiments reported here show
      that all PHN neurons (PHNn) show marked phasic behavior, which is highly
      oscillatory in approximately 25% of the population. The behavior of this subset
      of PHNn, referred to as type D PHNn, is clearly different from that of the medial
      vestibular nucleus neurons, which transmit the bulk of head velocity-related
      sensory vestibular inputs without integrating them. We have investigated the
      firing and biophysical properties of PHNn and developed data-based realistic
      neuronal models to quantitatively illustrate that their active conductances can
      produce the oscillatory behavior. Although some individual type D PHNn are able
      to show some features of mathematical integration, the lack of robustness of this
      behavior strongly suggests that additional network interactions, likely involving
      all types of PHNn, are essential for the neuronal integrator. Furthermore, the
      relationship between the impulse activity and membrane potential of type D PHNn
      is highly nonlinear and frequency-dependent, even for relatively small-amplitude
      responses. These results suggest that some of the synaptic input to type D PHNn
      is likely to evoke oscillatory responses that will be nonlinearly amplified as
      the spike discharge rate increases. It would appear that the PHNn have specific
      intrinsic properties that, in conjunction with network interconnections, enhance
      the persistent neural activity needed for their function.

PMID- 16598062
TI  - Sensorimotor cortex ablation prevents H-reflex up-conditioning and causes a
      paradoxical response to down-conditioning in rats.
AB  - Operant conditioning of the H-reflex, a simple model for skill acquisition,
      requires the corticospinal tract (CST) and does not require other major
      descending pathways. To further explore its mechanisms, we assessed the effects
      of ablating contralateral sensorimotor cortex (cSMC). In 22 Sprague-Dawley rats,
      the hindlimb area of left cSMC was ablated. EMG electrodes were implanted in the
      right soleus muscle and a stimulating cuff was placed around the right posterior
      tibial nerve. When EMG remained in a specified range, nerve stimulation just
      above the M response threshold elicited the H-reflex. In control mode, no reward
      occurred. In conditioning mode, reward occurred if H-reflex size was above (HRup
      mode) or below (HRdown mode) a criterion value. After exposure to the control
      mode for > or = 10 days, each rat was exposed for another 50 days to the control
      mode, the HRup mode, or the HRdown mode. In control and HRup rats, final H-reflex
      size was not significantly different from initial H-reflex size. In contrast, in
      HRdown rats, final H-reflex size was significantly increased to an average of
      136% of initial size. Thus like recent CST transection, cSMC ablation greatly
      impaired up-conditioning. However, unlike recent CST transection, cSMC produced a
      paradoxical response to down-conditioning: the H-reflex actually increased. These
      results confirm the critical role of cSMC in H-reflex conditioning and suggest
      that this role extends beyond producing essential CST activity. Its interactions
      with ipsilateral SMC or other areas contribute to the complex pattern of spinal
      and supraspinal plasticity that underlies H-reflex conditioning.

PMID- 16598063
TI  - Multivesicular release at developing Schaffer collateral-CA1 synapses: an
      analytic approach to describe experimental data.
AB  - We developed and analytically solved a simple and general stochastic model to
      distinguish the univesicular from the multivesicular mode of glutamate release.
      The model solution gives analytical mathematical expressions for average values
      of quantities that can be measured experimentally. Comparison of these quantities
      with the experimental measures allows one to discriminate the release mode and to
      determine the most probable values of model parameters. The model has been
      validated at glutamatergic CA3-CA1 synapses in the hippocampus from newborn (P1
      P5 old) rats. Our results strongly support a multivesicular type of release
      process requiring a variable pool of immediately releasable vesicles. Moreover,
      computing quantities that are functions of the model parameters, the mean
      amplitude of the synaptic response to the release of a single vesicle (q) was
      estimated to be 5-10 pA, in very good agreement with experimental findings. In
      addition a multivesicular type of release was supported by the following
      experimental evidences: 1) a high variability of the amplitude of successes, with
      a coefficient of variation ranging from 0.12 to 0.73; 2) an average potency ratio
      a2/a1 between the second and first response to a pair of stimuli >1; and 3)
      changes in the potency of the synaptic response to the first stimulus when the
      release probability was modified by increasing or decreasing the extracellular
      calcium concentration. Our results indicate that at Schaffer collateral-CA1
      synapses of the neonatal rat hippocampus a single action potential may induce the
      release of more than one vesicle from the same release site.

PMID- 16598064
TI  - Voltage-gated sodium channels in cerebellar Purkinje cells of mormyrid fish.
AB  - Cerebellar Purkinje cells of mormyrid fish differ in some morphological as well
      as physiological parameters from their counterparts in mammals. Morphologically,
      Purkinje cells of mormyrids have larger dendrites that are characterized by a
      lower degree of branching in the molecular layer. Physiologically, there are
      differences in electrophysiological response patterns that are related to sodium
      channel activity: first, sodium spikes in mormyrid Purkinje cells have low
      amplitudes, typically not exceeding 30 mV. Second, the response to climbing fiber
      stimulation in mormyrid Purkinje cells does not consist of a complex spike (with
      an initial fast sodium spike) as in mammals, but instead it consists of an all-or
      none excitatory postsynaptic potential, the so-called climbing fiber response.
      Because of these unique properties, we have begun to characterize mormyrid
      Purkinje cells electrophysiologically. In this study, we provide a description of
      voltage-gated Na+ channels and conductances in Purkinje cells of the mormyrid
      fish Gnathonemus petersii. Various types of Na+ channel alpha-subunits, i.e.,
      Nav1.1, Nav1.2, and Nav1.6, have been described in rodent Purkinje cells. Using
      immunohistochemical techniques, we found that these subunits are present in
      Purkinje cells of mormyrids. To test whether these Na+ channel subunits can
      mediate fast inactivating and resurgent Na+ currents in Gnathonemus Purkinje
      cells, we conducted patch-clamp recordings in acutely dissociated cells and in
      cerebellar slices. Both types of Na+ currents could be measured in rat and fish
      Purkinje cells. These data show that, despite prominent differences in
      electrophysiological response characteristics, Purkinje cells of rats and
      mormyrids share the same voltage-gated Na+ conductances.

PMID- 16598061
TI  - Realistic modeling of entorhinal cortex field potentials and interpretation of
      epileptic activity in the guinea pig isolated brain preparation.
AB  - Mechanisms underlying epileptic activities recorded from entorhinal cortex (EC)
      were studied through a computational model based on review of cytoarchitectonic
      and neurobiological data about this structure. The purpose of this study is to
      describe and use this model to interpret epileptiform discharge patterns recorded
      in an experimental model of ictogenesis (guinea pig isolated brain perfused with
      bicuculline). A macroscopic modeling approach representing synaptic interactions
      between cells subpopulations in the EC was chosen for its adequacy to mimic field
      potentials reflecting overall dynamics rising from interconnected cells
      populations. Therefore intrinsic properties of neurons were not included in the
      modeling design. Model parameters were adjusted from an identification procedure
      based on quantitative comparison between real and simulated signals. For both EC
      deep and superficial layers, results show that the model generates very realistic
      signals regarding temporal dynamics, spectral features, and cross-correlation
      values. These simulations allowed us to infer information about the evolution of
      synaptic transmission between principal cell and interneuronal populations and
      about connectivity between deep and superficial layers during the transition from
      background to ictal activity. In the model, this transition was obtained for
      increased excitation in deep versus superficial layers. Transitions between
      epileptiform activities [interictal spikes, fast onset activity (25 Hz), ictal
      bursting activity] were explained by changes of parameters mainly related to
      GABAergic interactions. Notably, the model predicted an important role of
      GABAa,fast- and GABAb-receptor-mediated inhibition in the generation of ictal
      fast onset and burst activities, respectively. These findings are discussed with
      respect to experimental data.

PMID- 16598065
TI  - Calmodulin regulates current density and frequency-dependent inhibition of sodium
      channel Nav1.8 in DRG neurons.
AB  - Sodium channel Nav1.8 produces a slowly inactivating, tetrodotoxin-resistant
      current, characterized by recovery from inactivation with fast and slow
      components, and contributes a substantial fraction of the current underlying the
      depolarizing phase of the action potential of dorsal root ganglion (DRG) neurons.
      Nav1.8 C-terminus carries a conserved calmodulin-binding isoleucine-glutamine
      (IQ) motif. We show here that calmodulin coimmunoprecipitates with endogenous
      Nav1.8 channels from native DRG, suggesting that the two proteins can interact in
      vivo. Treatment of native DRG neurons with a calmodulin-binding peptide (CBP)
      reduced the current density of Nav1.8 by nearly 65%, without changing voltage
      dependency of activation or steady-state inactivation. To investigate the
      functional role of CaM binding to the IQ motif in the Nav1.8 C-terminus, the IQ
      dipeptide was substituted by DE; we show that this impairs the binding of CaM to
      the IQ motif. Mutant Nav1.8IQ/DE channels produce currents with roughly 50%
      amplitude, but with unchanged voltage dependency of activation and inactivation
      when expressed in DRG neurons from Nav1.8-null mice. We also show that blocking
      the interaction of CaM and Nav1.8 using CBP or the IQ/DE substitution causes a
      buildup of inactivated channels and, in the case of the IQ/DE mutation,
      stimulation even at a low frequency of 0.1 Hz significantly enhances the
      frequency-dependent inhibition of the Nav1.8 current. This study presents, for
      the first time, evidence that calmodulin associates with a sodium channel,
      Nav1.8, in native neurons, and demonstrates a regulation of Nav1.8 currents that
      can significantly affect electrogenesis of DRG neurons in which Nav1.8 is
      normally expressed.

PMID- 16598066
TI  - Symmetric interactions within a homogeneous starburst cell network can lead to
      robust asymmetries in dendrites of starburst amacrine cells.
AB  - Starburst amacrine cells in the mammalian retina respond asymmetrically to
      movement along their dendrites; centrifugal movement elicits stronger responses
      in each dendrite than centripetal movement. It has been suggested that the
      asymmetrical response can be attributed to intrinsic properties of the processes
      themselves. But starburst cells are known to release and have receptors for both
      GABA and acetylcholine. We tested whether interactions within the starburst cell
      network can contribute to their directional response properties. In a
      computational model of interacting starburst amacrine cells, we simulated the
      response of individual dendrites to moving light stimuli. By setting the model
      parameters for "synaptic connection strength" (cs) to positive or negative
      values, overlapping starburst dendrites could either excite or inhibit each
      other. For some values of cs, we observed a very robust inward/outward asymmetry
      of the starburst dendrites consistent with the reported physiological findings.
      This is the case, for example, if a starburst cell receives inhibition from other
      starburst cells located in its surround. For other values of cs, individual
      dendrites can respond best either to inward movement or respond symmetrically. A
      properly wired network of starburst cells can therefore account for the
      experimentally observed asymmetry of their response to movement, independent of
      any internal biophysical or biochemical properties of starburst cell dendrites.

PMID- 16598067
TI  - Emergence of hearing in the chicken embryo.
AB  - It is commonly held that hearing generally begins on incubation day 12 (E12) in
      the chicken embryo (Gallus domesticus). However, little is known about the
      response properties of cochlear ganglion neurons for ages younger than E18. We
      studied ganglion neurons innervating the basilar papilla of embryos (E12-E18) and
      hatchlings (P13-P15). We asked first, when do primary afferent neurons begin to
      encode sounds? Second, when do afferents evidence frequency selectivity? Third,
      what range of characteristic frequencies (CFs) is represented in the late embryo?
      Finally, how does sound transfer from air to the cochlea affect responses in the
      embryo and hatchling? Responses to airborne sound were compared with responses to
      direct columella footplate stimulation of the cochlea. Cochlear ganglion neurons
      exhibited a profound insensitivity to sound from E12 to E16 (stages 39-42).
      Responses to sound and frequency selectivity emerged at about E15. Frequency
      selectivity matured rapidly from E16 to E18 (stages 42 and 44) to reflect a
      mature range of CFs (170-4,478 Hz) and response sensitivity to footplate
      stimulation. Limited high-frequency sound transfer from air to the cochlea
      restricted the response to airborne sound in the late embryo. Two periods of
      ontogeny are proposed. First is a prehearing period (roughly E12-E16) of
      endogenous cochlear signaling that provides neurotrophic support and guides
      normal developmental refinements in central binaural processing pathways followed
      by a period (roughly E16-E19) wherein the cochlea begins to detect and encode
      sound.

PMID- 16598068
TI  - Midbrain periaqueductal gray and vocal patterning in a teleost fish.
AB  - Midbrain structures, including the periaqueductal gray (PAG), are essential nodes
      in vertebrate motor circuits controlling a broad range of behaviors, from
      locomotion to complex social behaviors such as vocalization. Few single-unit
      recording studies, so far all in mammals, have investigated the PAG's role in the
      temporal patterning of these behaviors. Midshipman fish use vocalization to
      signal social intent in territorial and courtship interactions. Evidence has
      implicated a region of their midbrain, located in a similar position as the
      mammalian PAG, in call production. Here, extracellular single-unit recordings of
      PAG neuronal activity were made during forebrain-evoked fictive vocalizations
      that mimic natural call types and reflect the rhythmic output of a known
      hindbrain-spinal pattern generator. The activity patterns of vocally active PAG
      neurons were mostly correlated with features related to fictive call initiation.
      However, spike trains in a subset of neurons predicted the duration of vocal
      output. Duration is the primary feature distinguishing call types used in
      different social contexts and these cells may play a role in directly
      establishing this temporal dimension of vocalization. Reversible, lidocaine
      inactivation experiments demonstrated the necessity of the midshipman PAG for
      fictive vocalization, whereas tract-tracing studies revealed the PAG's
      connectivity to vocal motor centers in the fore- and hindbrain comparable to that
      in mammals. Together, these data support the hypotheses that the midbrain PAG of
      teleosts plays an essential role in vocalization and is convergent in both its
      functional and structural organization to the PAG of mammals.

PMID- 16598071
TI  - Patient-controlled analgesia: Finding a balance between cost and comfort.
AB  - PURPOSE: Despite the growing movement in acute pain management, acute
      postoperative pain continues to be undermanaged. Although numerous clinical
      practice guidelines for pain management have been published throughout the last
      12 years, inadequate pain relief remains a significant health care issue.
      Insufficient dosage of analgesics is a common problem, and therapy for those
      patients still with pain represents a considerable health care dilemma. SUMMARY:
      Patient-controlled analgesia (PCA) refers to a process in which patients
      determine when and how much medication they receive, regardless of analgesic
      technique. Patient-controlled modalities using intravenous (i.v.) and epidural
      routes have dramatically improved postoperative pain management. PCA has emerged
      as an effective way for patients to manage their pain, allowing self
      administration of small doses of analgesics to maintain a certain level of pain
      control. PCA is most commonly delivered via an intravenous or epidural route, and
      while patient satisfaction is higher with PCA than with conventional methods of
      analgesic administration, the invasiveness, costs, health care resources, and
      risk of errors associated with currently available modalities may limit their
      utility. The overall effectiveness of any analgesic technique depends on both the
      degree of pain relief and the incidence of side effects or complications. These
      adverse events of acute pain complicate postoperative recovery and may lead to
      longer hospital stays, as well as increased health care costs. Several new PCA
      modalities are being developed to address these limitations. These systems
      deliver drugs through a variety of routes (for example, transdermal). Most
      notable is a self-contained, credit card-sized fentanyl transdermal patient
      activated system. It provides pain relief therapeutically equivalent to that of
      standard regimen of morphine i.v. PCA, with pharmacokinetics similar to those of
      intravenous fentanyl infusion. Fentanyl HCl patient-activated transdermal systems
      (PATS) may be an effective, noninvasive alternative to currently available i.v.
      PCA modalities. Whichever drug or device is utilized, the overall success relies
      on the expert supervision of nurses, pharmacists, and anesthesiologists in an
      acute pain service. CONCLUSION: Current PCA techniques using i.v. or epidural
      administration have limitations. Development of new technology offering
      alternative routes for PCA administration is at the forefronts of PCA research.

PMID- 16598069
TI  - Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of
      adult brain tumors.
AB  - Genes involved in phase I and phase II regulation of aromatic hydrocarbon-induced
      effects exhibit sequence variability that may mediate the risk of adult brain
      tumors. We evaluated associations between gene variants in CYP1A1, CYP1B1, GSTM3,
      EPHX1, and NQO1 and adult brain tumor incidence. Cases were patients with glioma
      (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) diagnosed from 1994
      to 1998 at three U.S. hospitals. Controls were 799 patients admitted to the same
      hospitals for nonmalignant conditions. DNA was extracted from blood samples
      collected from 1277 subjects, and genotyping was conducted for CYP1A1 I462V,
      CYP1B1 V432L, EPHX1 Y113H, GSTM3 *A/*B (intron 6 deletion), and NQO1 P187S. The
      CYP1B1 V432L homozygous variant was associated with decreased risk of meningioma
      (odds ratio [OR] = 0.6; 95% CI, 0.3-1.0) but not the other tumor types. The GSTM3
      *B/*B genotype was associated with increased risk of glioma (OR = 2.3; 95% CI,
      1.0-5.2) and meningioma (OR = 3.6; 95% CI, 1.3-9.8). Increased risks associated
      with GSTM3 *B/*B were observed in younger subjects (age < 50) and older subjects
      (age > or = 50), in men and women, and within each study site. The magnitude of
      association for GSTM3 with glioma and meningioma was greater among ever-smokers
      than among those who had never smoked. None of the other genotypes showed
      consistent associations with any tumor type. The association with the GSTM3 *B
      allele, while intriguing, requires replication, and additional research is needed
      to clarify the function of the GSTM3 alleles studied here.

PMID- 16598072
TI  - A novel magnetic resonance-based method to measure gene expression in living
      cells.
AB  - In unicellular and multicellular eukaryotes, elaborate gene regulatory mechanisms
      facilitate a broad range of biological processes from cell division to
      morphological differentiation. In order to fully understand the gene regulatory
      networks involved in these biological processes, the spatial and temporal
      patterns of expression of many thousands of genes will need to be determined in
      real time in living organisms. Currently available techniques are not sufficient
      to achieve this goal; however, novel methods based on magnetic resonance (MR)
      imaging may be particularly useful for sensitive detection of gene expression in
      opaque tissues. This report describes a novel reporter gene system that monitors
      gene expression dynamically and quantitatively, in yeast cells, by measuring the
      accumulation of inorganic polyphosphate (polyP) using MR spectroscopy (MRS) or MR
      spectroscopic imaging (MRI). Because this system is completely non-invasive and
      does not require exogenous substrates, it is a powerful tool for studying gene
      expression in multicellular organisms, as well.

PMID- 16598073
TI  - 'Evidence of an auxin signal pathway, microRNA167-ARF8-GH3, and its response to
      exogenous auxin in cultured rice cells'.
AB  - MicroRNA167 (miR167) was shown to cleave auxin responsive factor 8 (ARF8) mRNA in
      cultured rice cells. MiR167 level was found to be controlled by the presence of
      auxin in the growth medium. When cells grew in auxin-free medium, miR167 level
      decreased, resulting in an increase in the level of ARF8 mRNA. Cells growing in
      the normal growth medium containing auxin showed a reversed trend. It was also
      shown that expression of OsGH3-2, an rice IAA-conjugating enzyme, was positively
      regulated by ARF8. Delivery of synthesized miR167 into cells led to decrease of
      both ARF8 mRNA and OsGH3-2 mRNA. This study provides an evidence in which the
      exogeneous auxin signal is transduced to OsGH3-2 through miR167 and ARF8 in
      sequence. This proposed auxin signal transduction pathway, auxin-miR167-ARF8
      OsGH3-2, could be, in conjunction with the other microRNA-mediated auxin signals,
      an important one for responding to exogeneous auxin and for determining the
      cellular free auxin level which guides appropriate auxin responses.

PMID- 16598076
TI  - The multifunctional GIT family of proteins.
AB  - The G-protein-coupled receptor (GPCR)-kinase-interacting proteins 1 and 2 (GIT1
      and GIT2) are ubiquitous multidomain proteins involved in diverse cellular
      processes. They traffic between three distinct cellular compartments (cytoplasmic
      complexes, focal adhesions and the cell periphery) through interactions with
      proteins including ARF, Rac1 and Cdc42 GTPases, p21-activated kinase (PAK), PAK
      interacting exchange factor (PIX), the kinase MEK1, phospholipase Cgamma
      (PLCgamma) and paxillin. GITs and PIX cooperate to form large oligomeric
      complexes to which other proteins are transiently recruited. Activation of Rac1
      and Cdc42 drives association of PAK with these oligomers, which unmasks the
      paxillin-binding site in GITs that recruits them to focal complexes. There, they
      regulate cytoskeletal dynamics by feedback inhibition of Rac1. GITs also
      participate in receptor internalization by regulating membrane trafficking
      between the plasma membrane and endosomes, targeting ARF GTPases through their
      ARF GTPase-activating protein (ARF-GAP) activity. Furthermore, GITs act as
      scaffolds to control spatial activation of several signaling molecules. Finally,
      recent results suggest pathogenic roles for GIT proteins in Huntington's disease
      and HIV infection.

PMID- 16598075
TI  - Human centromeric alphoid domains are periodically homogenized so that they vary
      substantially between homologues. Mechanism and implications for centromere
      functioning.
AB  - Sequence analysis of alphoid repeats from human chromosomes 17, 21 and 13 reveals
      recurrent diagnostic variant nucleotides. Their combinations define haplotypes,
      with higher order repeats (HORs) containing identical or closely-related
      haplotypes tandemly arranged into separate domains. The haplotypes found on
      homologues can be totally different, while HORs remain 99.8% homogeneous both
      intrachromosomally and between homologues. These results support the hypothesis,
      never before demonstrated, that unequal crossovers between sister chromatids
      accumulate to produce homogenization and amplification into tandem alphoid
      repeats. I propose that the molecular basis of this involves the diagnostic
      variant nucleotides, which enable pairing between HORs with identical or closely
      related haplotypes. Domains are thus periodically renewed to maintain high
      intrachromosomal and interhomologue homogeneity. The capacity of a domain to form
      an active centromere is maintained as long as neither retrotransposons nor
      significant numbers of mutations affect it. In the presented model, a chromosome
      with an altered centromere can be transiently rescued by forming a neocentromere,
      until a restored, fully-competent domain is amplified de novo or rehomogenized
      through the accumulation of unequal crossovers.

PMID- 16598074
TI  - Molecular basis of the targeting of topoisomerase II-mediated DNA cleavage by
      VP16 derivatives conjugated to triplex-forming oligonucleotides.
AB  - Human topoisomerase II (topo II) is the cellular target for a number of widely
      used antitumor agents, such as etoposide (VP16). These agents 'poison' the enzyme
      and induce it to generate DNA breaks that are lethal to the cell. Topo II
      targeted drugs show a limited sequence preference, triggering double-stranded
      breaks throughout the genome. Circumstantial evidence strongly suggests that some
      of these breaks induce chromosomal translocations that lead to specific types of
      leukaemia (called treatment-related or secondary leukaemia). Therefore, efforts
      are ongoing to decrease these secondary effects. An interesting option is to
      increase the sequence-specificity of topo II-targeted drugs by attaching them to
      triplex-forming oligonucleotides (TFO) that bind to DNA in a highly sequence
      specific manner. Here five derivatives of VP16 were attached to TFOs. The active
      topo II poisons, once linked, induced cleavage 13-14 bp from the triplex end
      where the drug was attached. The use of triple-helical DNA structures offers an
      efficient strategy for targeting topo II-mediated cleavage to DNA specific
      sequences. Finally, drug-TFO conjugates are useful tools to investigate the
      mechanistic details of topo II poisoning.

PMID- 16598077
TI  - Paradigm shifts, orthopaedics, and clinical research.

PMID- 16598078
TI  - Sensory innervation of temporomandibular joint disk.
AB  - PURPOSE: To investigate the nerve endings of the adult temporomandibular joint
      disk, in particular the presence and configuration of the sensory nerve endings
      by silver staining and electron microscopy. METHODS: 20 cadaveric
      temporomandibular joints impregnated with silver stain were studied using an
      optical microscope; 2 other joints were studied using a transmission electron
      microscope. RESULTS: Free nerve endings were found in the disk parenchyma of all
      joints. Golgi-Mazzoni corpuscles, Ruffini corpuscles, and articular corpuscles
      were also observed as sensory nerve end organs. Myelinated and nonmyelinated
      nerve fibres were visualised in the disk parenchyma using the transmission
      electron microscope. CONCLUSION: Free nerve endings and sensory nerve end organs
      are present in the disk parenchyma of the human temporomandibular joint and are
      associated with sensation and proprioception, just as they are in the acetabular
      labrum, glenoid labrum, triangular fibrocartilage complex, and meniscus.

PMID- 16598079
TI  - Prevalence of osteoarthritis, osteoporotic vertebral fractures, and
      spondylolisthesis among the elderly in a Japanese village.
AB  - PURPOSE: To study the prevalence of osteoarthritis, osteoporotic vertebral
      fractures, and spondylolisthesis among elderly residents of a Japanese village
      and to examine the correlation between radiographic evidence of abnormality and
      lower back pain. METHODS: 205 men (mean age, 70.7 years) and 323 women (mean age,
      70.5 years) in a Japanese village participated in this cross-sectional study.
      Plain lateral radiographs were taken from the lower thoracic spine to the sacral
      spine. They were evaluated by 3 independent orthopaedic surgeons for degree of
      osteoarthritis (using Weiner grading system) and the presence of osteoporotic
      vertebral fractures and spondylolisthesis. RESULTS: The prevalence of
      osteoarthritis in elderly Japanese villagers was 38.3%, whereas that of
      osteoporotic vertebral fractures and spondylolisthesis was 17.8% and 8.9%,
      respectively. There was no significant difference in osteoarthritis between men
      and women, but osteoporotic vertebral fractures and spondylolisthesis were
      significantly more common in females (p<0.01). No significant correlation was
      observed between lower back pain and radiographic evidence of degenerative spinal
      disease. CONCLUSION: The prevalence of spondylolisthesis in elderly Japanese was
      much lower than that in whites or African Americans. The prevalence of
      osteoarthritis or osteoporotic vertebral fractures was comparable with other
      English or US studies. Radiographic evidence of osteoarthritis, osteoporotic
      vertebral fractures, and spondylolisthesis is not necessarily associated with
      lower back pain.

PMID- 16598080
TI  - Prevalence and surgical significance of a high-origin anterior tibial artery.
AB  - PURPOSE: To assess the prevalence of proximal high-origin anterior tibial artery
      and its surgical significance. METHODS: 100 knees were prospectively studied
      using colour Doppler ultrasonography. No patient had a history of lower-limb
      arterial pathology or previous knee surgery. All ultrasound images were assessed
      by a single experienced vascular technician to eliminate inter-observer
      variability. RESULTS: The mean age of the patients was 56 years (range, 21-96
      years). Prevalence of the high-origin anterior tibial arterial pattern was 6%,
      greater than that reported by previous angiographic or cadaveric studies. In all
      patients with high-origin anterior tibial artery, the artery was in direct
      contact with the posterior cortex of the tibia. CONCLUSION: This highlights the
      danger of using sharp instruments in knee procedures that involve extension of
      osteotomy to the posterior tibial cortex, particularly high-tibial osteotomy and
      total knee replacement. Knowledge of the anatomical variations in the branching
      of the popliteal artery is important because damage to its branches can be limb-
      or life-threatening.

PMID- 16598081
TI  - Assessment of bony union following surgical stabilisation for lumbar
      spondylolysis: a comparative study between radiography and computed tomography.
AB  - PURPOSE: To compare the status of bony union seen on plain radiography versus
      computed tomography (CT) following tension band repair for refractory
      spondylolysis. METHODS: 14 patients (12 men and 2 women; mean age, 23 years; age
      range, 16-56 years) with a mean follow-up period of 6.35 years were included. All
      patients were operated on by one senior surgeon using either a Scott procedure
      (n=2) or van Dam modification of the Scott procedure (n=12). Bony union of the
      pars was assessed using both plain radiography (anteroposterior, lateral, and
      oblique views) and reverse gantry CT. The presence of bony union was determined
      if a bridging bone was shown in the images. The Oswestry Disability Index was
      measured at 6-year follow-up. RESULTS: 13 (93%) of 14 patients showed bony union
      on plain/oblique radiographs versus 7 (50%) on CT scan. The mean Oswestry
      Disability Index was 28 (good to excellent). The high incidence of nonunion shown
      on CT scanning did not correlate well with clinical results. CONCLUSION: Bony
      nonunion is more difficult to visualise on plain radiographs than reverse gantry
      CT. CT demonstrates more clearly the presence or absence of the bridging bone.
      Clinical results do not correlate with bony union, indicating that bony union is
      not required to achieve good results.

PMID- 16598082
TI  - Posterior lumbar interbody fusion versus intertransverse fusion in the treatment
      of lumbar spondylolisthesis.
AB  - PURPOSE: To compare 2 methods of fusion in the treatment of lumbar
      spondylolisthesis: posterior lumbar interbody fusion (PLIF) and intertransverse
      fusion (ITF). METHODS: 20 patients with lumbar spondylolisthesis were randomly
      allocated to one of 2 groups: decompression, posterior instrumentation, and PLIF
      (n=10) or decompression, posterior instrumentation, and ITF (n=10). The Oswestry
      low back pain disability questionnaire was used for clinical assessment.
      Radiography was performed preoperatively and postoperatively to assess the
      reduction of spondylolisthesis or slip. RESULTS: In the PLIF and ITF groups,
      87.5% and 100% had a satisfactory clinical result, and 48% and 39% had reduced
      spondylolisthesis, respectively. Both had a fusion rate of 100%. PLIF showed
      better reduction of spondylolisthesis, although ITF achieved a better subjective
      and clinical outcome. CONCLUSION: Morbidity and complications are much higher
      following PLIF than ITF. ITF is recommended because of the simplicity of the
      procedure, lower complication rate, and good clinical and radiological results.

PMID- 16598083
TI  - Acetabular morphometry for determining hip dysplasia in the Singaporean
      population.
AB  - PURPOSE: To assess and evaluate the usefulness of 7 morphological measurements of
      the acetabulum in establishing the prevalence of acetabular dysplasia in the
      Singaporean population. METHODS: Standardised plain anteroposterior radiographs
      of 522 hip joints of 261 asymptomatic patients (mean age, 60 years; range, 16-99
      years) were evaluated. The 7 morphological measurements were centre-edge angle,
      acetabular angle, depth-to-width ratio, roof obliquity, extrusion index, lateral
      subluxation, and peak-to-edge distance. RESULTS: 19 (7.3%) patients were
      acetabular dysplastic (centre-edge angle of <20 degrees). The mean centre-edge
      angle was 31.2 degrees (range, 5-52 degrees), acetabular angle 39.46 degrees
      (range, 10-58 degrees), depth-to-width ratio 0.32, roof obliquity 7.86 degrees,
      extrusion index 0.18, lateral subluxation 9.9 mm, and the peak-to-edge distance
      15.65 mm. CONCLUSION: Centre-edge angle was the most useful measurement and
      correlated significantly with acetabular angle, extrusion index, peak-to-edge
      distance, and roof obliquity. These preliminary results show a relatively higher
      rate (7.3%) of acetabular dysplasia in the Singaporean population, compared with
      other similar but larger Asian studies performed in Hong Kong (1.1%) and Korea
      (1.8%).

PMID- 16598084
TI  - Bone remodelling after total hip arthroplasty using an uncemented anatomic
      femoral stem: a three-year prospective study using bone densitometry.
AB  - PURPOSE: To evaluate the clinical, radiological, and densitometric changes in the
      bone-remodelling patterns of femoral stems aligned in neutral, valgus, or varus
      positions. METHODS: Between February and October 2000, 70 patients underwent
      unilateral total hip arthroplasty for primary osteoarthritis using an uncemented
      Anatomique Benoist Girard (ABG) II stem. 69 patients (30 males and 39 females)
      with a mean age of 59 years (range, 38-76 years) and a mean body weight of 79.3
      kg (range, 29-110 kg) completed 3 years' follow-up on bone remodelling. The
      clinical, radiological, and densitometric changes of the neutral, valgus, and
      varus groups were evaluated, and the difference in bone-remodelling patterns
      between the 3 groups was analysed. RESULTS: 54 patients had neutrally placed
      stems, while varus and valgus malalignment occurred in 6 and 9 patients,
      respectively. Clinical and radiological evaluations were very similar among the 3
      groups. Only densitometry could detect traceable changes resulting from the
      differing biomechanics of the neutral, varus, and valgus stem alignments.
      CONCLUSION: The ABG II stem design made moderate errors in alignment
      biomechanically tolerable. Alignment defects had no clinical consequences and
      resulted in minimal differences in bone remodelling.

PMID- 16598086
TI  - Early results of prosthetic hip replacement for femoral neck fracture in active
      elderly patients.
AB  - PURPOSE: To evaluate the short-term clinical and functional outcomes of total hip
      arthroplasty performed for physiologically active elderly patients with Garden
      type-3 or -4 femoral neck fracture. METHODS: Records of 47 consecutive patients
      (40 female, 7 male) with type-3 or -4 femoral neck fracture (Garden
      classification) who underwent cemented total hip arthroplasty at our hospital
      during January 1999 to December 2002 were reviewed. Radiological and clinical
      (Harris functional hip score and Oxford hip score) assessments of 38 patients
      were measured with a mean follow-up period of 21 months (range, 4-48 months).
      RESULTS: The mean age of the 47 patients was 75 years (range, 62-89 years).
      Records of 9 patients were excluded because of death, lost to follow-up, and
      development of deep infection that necessitated implant removal and excision
      arthroplasty. The mean Harris hip score of the 38 patients was 83 (range, 59-97),
      whereas the mean Oxford hip score was 25.2 (range, 14-33). Pain in the hips was
      absent in 30 patients, 6 had slight pain occasionally, and 2 patients had mild-to
      moderate hip discomfort. No signs of aseptic loosening or change in implant
      position were noted on radiographic assessment. Two cases of dislocation were
      reduced by closed reduction. Two patients had deep wound infection and were
      treated with debridement, implant removal, and conversion to girdle stone.
      CONCLUSION: This short-term study showed that total hip arthroplasty for femoral
      neck fracture had good postoperative results in functional hip and pain scores.
      More attention should be paid to coexisting medical illness (e.g. diabetes
      mellitus, hypertension, and ischaemic heart disease) and prevention of infection.

PMID- 16598085
TI  - Safeness of Simplex-tobramycin bone cement in patients with renal dysfunction
      undergoing total hip replacement.
AB  - PURPOSE: To compare the pharmacokinetic profile of tobramycin in blood, urine,
      and at the operative site following the use of Simplex-tobramycin bone cement in
      primary total hip replacement between patients with and without renal
      dysfunction. METHODS: Six patients with renal dysfunction underwent cemented
      primary total hip replacement for osteoarthritis. The elution characteristics of
      Simplex-tobramycin bone cement in the 6 patients with renal dysfunction were
      compared with 9 patients who had normal renal function. Blood, urine, and
      drainage fluid specimens were collected for 72 hours postoperatively. RESULTS:
      Very high concentrations of tobramycin were seen in the drainage fluid of the 2
      groups. Mean serum tobramycin levels peaked at postoperative 3 hours, and
      declined rapidly to negligible levels at 72 hours in both groups. Mean urinary
      tobramycin concentrations peaked at postoperative 12 hours and declined rapidly
      until 48 hours in both groups. Urinary tobramycin was excreted significantly more
      slowly in renal dysfunction group in the first 12 hours, but not thereafter.
      Although serum creatinine levels of the renal dysfunction group were higher
      throughout the study period, the difference was not significant. Both groups
      achieved excellent local delivery of the antibiotic with minimal systemic
      concentrations. CONCLUSION: Simplex-tobramycin bone cement appears to be an
      effective and safe means to deliver antibiotic for patients with renal
      dysfunction who undergo total hip replacement.

PMID- 16598087
TI  - Comparison of early postoperative rehabilitation outcome following total knee
      arthroplasty using different surgical approaches and instrumentation.
AB  - PURPOSE: To assess early postoperative rehabilitation outcome following computer
      assisted total knee arthroplasty (TKA) or standard instrumentation TKA using a
      medial parapatellar or subvastus approach. METHODS: A prospective controlled
      trial of 70 consecutive patients undergoing TKA with a low contact stress
      rotating platform prosthesis was conducted. Patients were randomised to receive
      surgery with either computer navigation or standard instrumentation. A medial
      parapatellar or subvastus approach was used according to the surgeons'
      preference. Outcome measures included preoperative knee function, intra-operative
      factors, and postoperative rehabilitation. RESULTS: Duration of surgery was
      significantly longer when using computer navigation; however, operating time
      decreased with greater experience. A higher incidence and duration of early
      postoperative quadriceps dysfunction was associated with computer-assisted TKA
      through the medial parapatellar approach than through the subvastus approach or
      TKA performed with standard instrumentation. No patient who received surgery
      through the subvastus approach had a lag of more than 20 degrees, at 48 hours
      postoperatively, regardless of the instrumentation used. CONCLUSION: Computer
      assisted TKA through a medial parapatellar approach was associated with delayed
      recovery of the quadriceps during early postoperative rehabilitation. This was
      due to the additional quadriceps dissection required to place the femoral
      tracking array. The subvastus approach is therefore recommended for computer
      assisted TKA.

PMID- 16598088
TI  - Open medial placement of Kirschner wires for supracondylar humeral fractures in
      children.
AB  - PURPOSE: To assess the efficacy of our protocol for treatment of displaced
      Gartland type-3 supracondylar fractures of the humerus in children. METHODS:
      Records of 43 children with displaced Gartland type-3 supracondylar fractures of
      the humerus admitted from October 1997 to October 2003 were reviewed. Patients
      were treated within 12 hours of admission by closed reduction (n=33) or open
      reduction (n=10). Crossed medial and lateral Kirschner wires through a medial
      approach were used in all patients. A 3-cm incision was made medially to identify
      the correct entry point of the medial wire, and thus prevent ulnar nerve injury.
      The incision was extendable for open reduction if closed reduction was
      unsuccessful. RESULTS: The mean age of the 43 patients was 7.2 years (range, 2-14
      years). The mean follow-up period was 48 months (range, 12-84 months). 83% of the
      fractures occurred in boys. All fractures were closed, extension type, with 28
      (65.1%) involved the right elbow. No patient had iatrogenic ulnar nerve injury.
      All patients showed satisfactory results according to Flynn criteria. CONCLUSION:
      If closed reduction is unsuccessful, open reduction and open medial placement of
      crossed Kirschner wires can provide reliable results. The small medial incision
      provides a viewing point for entry of the wire and prevents iatrogenic injury of
      the ulnar nerve. It is cosmetically more acceptable and can be extended to
      facilitate open reduction.

PMID- 16598089
TI  - Basal thumb metacarpal osteotomy for trapeziometacarpal osteoarthritis.
AB  - PURPOSE: To review the subjective and functional results of basal thumb
      metacarpal osteotomy for the treatment of trapeziometacarpal osteoarthritis.
      METHODS: Between July 1993 and November 1998, 35 thumb osteotomies without
      internal fixation were performed on 33 patients in the Christchurch Hospital, New
      Zealand. Records of 28 thumbs (13 right and 15 left) of 26 patients (17 women and
      9 men) were available for review. Patients were reviewed using strength testing
      and the Michigan Hand Outcomes Questionnaire. RESULTS: The mean age of the 26
      patients was 54 years (range, 30-69 years). Of the 28 thumbs, 22 (21 patients)
      had good or excellent results, 2 fair, one poor. The remaining 3 thumbs (3
      patients) required further revision and were classified as failures. The mean
      follow-up period of the 25 thumbs (24 patients) not requiring revision was 34
      months (range, 12-73 months). Good thumb motion was present in all hands with no
      trapeziometacarpal instability seen. Compared with the normative data, the
      strengths of key pinch, pulp pinch, and tripod pinch of our patients were
      significantly lower (22-32% lower), but not the grip strength. Michigan Hand
      Outcomes Questionnaire scores increased 28 (range, 1-56) points after surgery,
      with significant improvement especially in pain (+44 points), activities of daily
      living (one-handed tasks, +41 points), and satisfaction (+35 points). CONCLUSION:
      Basal thumb metacarpal osteotomy is a straightforward, conservative procedure
      that should be considered for grades II and III trapeziometacarpal
      osteoarthritis.

PMID- 16598090
TI  - Residual nonunion following vascularised fibular graft treatment for congenital
      pseudarthrosis of the tibia: a report of two cases.
AB  - Resection and reconstruction using a vascularised fibular graft is a viable
      alternative treatment for congenital pseudarthrosis of the tibia, although distal
      junctional nonunion and residual deformity are known complications that are
      difficult to treat. We illustrate 2 cases in which bony union was achieved
      following a technique using fibular grafting and intramedullary nailing, without
      additional bone grafting. This technique was feasible because of hypertrophy of
      the fibular graft.

PMID- 16598091
TI  - Rapidly progressive necrotising fasciitis following a stonefish sting: a report
      of two cases.
AB  - Two patients developed rapidly progressive necrotising fasciitis after being
      stung by a stonefish. Both were given a hot-water bath for pain relief. The hot
      water may have accelerated bacterial growth and the consequent development of
      necrotising fasciitis. Vibrio vulnificus was cultured from one patient. It is
      recommended that patients should receive high dose of oral and intravenous
      antibiotic prophylaxis for vibrio prevention. Antibiotics should be given before
      or during, not after, a hot-water bath, and the patient's condition should be
      monitored closely.

PMID- 16598092
TI  - Intradural spinal tuberculosis in the absence of vertebral or meningeal
      tuberculosis: a case report.
AB  - We present a patient with spinal intradural tuberculosis in the absence of both
      vertebral and meningeal tuberculosis. Diagnosis was made based on intra-operative
      findings and was confirmed by histopathology. Early surgical decompression along
      with a combination of steroid and antitubercular therapy resulted in a good
      outcome. At 26-month follow-up, the patient regained bladder control and was able
      to walk with support. Clinical features, magnetic resonance imaging, and intra
      operative findings are described. Pathology and the relevant literature are
      discussed.

PMID- 16598093
TI  - Pigmented villonodular synovitis of the hip mimicking soft-tissue sarcoma: a case
      report.
AB  - Pigmented villonodular synovitis is a rare and benign but potentially locally
      aggressive disease that should be considered in younger patients who present with
      monoarticular joint symptoms and pathology. We present a 30-year-old Sudanese
      woman with a huge mass arising from the right hip joint. A multimodality
      radiological approach to investigation and diagnosis is demonstrated and
      discussed. Histopathological examination of the resected specimen confirmed the
      diagnosis of pigmented villonodular synovitis with the mass consisting of a
      proliferation of fibrohistiocytic cells, abundant haemosiderin, foamy
      histiocytes, and occasional giant cells. The patient made a good recovery, with
      mobility aided by arm crutches and a hip abduction brace.

PMID- 16598094
TI  - An unusual presentation of eosinophilic granuloma in an adult: a case report.
AB  - Eosinophilic granuloma is the most common and benign form of a rare proliferative
      disorder: Langerhans' cell histiocytosis. Spinal involvement is rare and only 15
      adult cases have been reported. We present an unusual variant of eosinophilic
      granuloma in a 25-year-old woman with radiological evidence of vertebra plana.
      Plain radiography, magnetic resonance imaging, bone scan, and blood tests were
      carried out, and a specimen was taken from L4 using computed tomography-guided
      biopsy. Gram staining, acid fast bacillus smear, bacterial and fungal cultures
      were negative. Histological examination of the biopsy showed features of
      eosinophilic granuloma with aggregates of Langerhans histiocytes. The patient was
      treated with low-grade radiotherapy at 150 cGy per day for 7 days. She was
      asymptomatic at one-year follow-up although the radiological picture was
      unchanged.

PMID- 16598095
TI  - Malignant intraosseous peripheral nerve sheath tumour of the proximal femur: a
      case report.
AB  - We report a rare case of an intraosseous malignant peripheral nerve sheath tumour
      of the femoral head and neck. The tumour presented as a well-defined radiolucent
      lesion on plain radiography. Computed tomography showed aggressive destruction of
      the bone with no involvement of the adjacent soft tissues. Magnetic resonance
      imaging revealed an isointense signal intensity on T1-weighted images,
      hyperintensity on T2-weighted images, and non-homogeneously increased signal
      intensity after administration of contrast media. The final diagnosis was based
      on pathohistologic analyses due to the non-specific nature of the lesion.

PMID- 16598096
TI  - Soft-tissue sarcoma mimicking large haematoma: a report of two cases and review
      of the literature.
AB  - We report on 2 patients with soft-tissue sarcomas mimicking large haematomas.
      Neither patient had a medical history of trauma or bleeding tendency. In a
      patient with a large leiomyosarcoma in the buttock, insufficient biopsy material
      from initial surgeries precluded a correct diagnosis. In the second patient with
      epithelioid sarcoma of the forearm, fasciotomy was repeatedly performed for
      compartment syndrome arising from the tumour. It is important to reconfirm prior
      trauma and investigate the clinical course and images of patients with an unusual
      history of haematoma in the extremities. The possibility of a malignant tumour
      should be suspected, and repeated biopsies should be performed if necessary.

PMID- 16598097
TI  - Breakage of intramedullary femoral guide rod during total knee arthroplasty: a
      case report.
AB  - We report a rare complication during primary total knee arthroplasty. An
      intramedullary femoral guide rod was broken during insertion. The broken part
      jammed into the isthmus of the femur. An initial attempt to push the broken rod
      via the proximal femur by a guide wire to the distal femur was unsuccessful
      because the broken rod was lodged in the isthmus. Ultimately, the isthmus was
      opened using a flexible 9-mm end-cutting reamer, and the broken rod was pushed
      down to the distal femoral entry site in an antegrade fashion under image
      intensification. Selecting a more medial entry site on the intercondylar notch
      with a smaller valgus cutting angle and using a shorter guide rod can avoid such
      a breakage.

PMID- 16598098
TI  - Total hip arthroplasty infected by Brucella: a report of two cases.
AB  - Infection caused by Brucella following total joint arthroplasty is very rare. We
      present 2 cases of brucellar infection following total hip arthroplasty (THA). A
      66-year-old woman who had prolonged contact with cattle presented with pain at
      the thigh and groin areas. The patient had undergone an uncemented THA for a hip
      fracture 3 years previously. Cultures of articular liquid were positive for
      Brucella abortus. The implant was loosened and was managed with a 2-stage re
      implantation. A 71-year-old man presented with painless suppuration of the hip
      joint through the scar from previous surgeries. Radiography demonstrated a well
      integrated THA. When postoperative cultures were found positive for Brucella
      melitensis, antibiotic treatment of rifampicin 900 mg, streptomycin 1 g, and
      doxycycline 200 mg daily were prescribed. At 5.5-year and 5-year follow-up,
      respectively, both patients were asymptomatic and free of infection with well
      integrated implants. As the Brucella pathogen is highly susceptible to
      antibiotics, standard 2-stage revision arthroplasty for loosened implant or
      debridement and antibiotic treatment for well-fixed implant should suffice.

PMID- 16598100
TI  - Massive calcaneal enthesopathy in a non-healing leg ulcer: a case report.

PMID- 16598099
TI  - Nicolau syndrome following intramuscular diclofenac administration: a case
      report.
AB  - Nicolau syndrome (livedoid dermatitis) is a rare adverse reaction of a still
      largely unidentified pathogenesis at the site of intramuscular drug injection.
      The typical presentation is pain around the injection site soon after injection,
      followed by erythema, livedoid patch, haemorrhagic patch, and finally necrosis of
      skin, subcutaneous fat, and muscle tissue. The phenomenon has been related to the
      administration of a variety of drugs, including non-steroidal anti-inflammatory
      drugs, corticosteroids, and penicillin. We report a case of Nicolau syndrome
      following an intramuscular injection of diclofenac. The large ulceration over the
      right buttock was positive for Pseudomonas aeruginosa, and histology revealed
      subcutaneous fat necrosis and non-specific inflammation with no evidence of
      malignancy or vasculitis. The lesion required multiple debridements and a partial
      thickness skin graft. Subcutaneous injection, rather than intramuscular
      injection, was found to be a determining factor in this case. Clinicians must be
      cautious in the use of proper injection procedures, including appropriate needle
      length, in order to minimise complications.

PMID- 16598101
TI  - Distal radial fracture treated with minimally invasive procedure.

PMID- 16598103
TI  - High-frequency mechanical vibration to recanalize chronic total occlusions after
      failure to cross with conventional guidewires.
AB  - BACKGROUND: Crossing chronic total occlusions (CTO) of coronary arteries
      continues to challenge interventional cardiologists. A clinical study was
      undertaken in four European centers to examine the feasibility of using the new
      CROSSER system that utilizes high-frequency mechanical vibration to penetrate
      atherosclerotic plaque material to cross CTOs in patients where conventional
      guidewire techniques had failed. The objective of the study was to determine
      whether the CROSSER system could safely cross such CTOs. PATIENTS AND METHODS: A
      total of 55 CTO lesions in 53 patients were treated in two clinical phases: (1)
      Phase 1 feasibility study (30 CTOs), with a primary focus on device safety; and
      (2) Phase 2 pivotal study (25 CTOs) using an improved version of the device, with
      a primary focus on effectiveness. RESULTS: The primary endpoint of device
      efficacy and the secondary endpoint of clinical success were both 76% (19 of 25)
      in the pivotal study phase. No major adverse cardiac events of death, Q-wave
      myocardial infarction or target lesion revascularization (by either coronary
      artery bypass graft surgery or percutaneous coronary intervention) were observed
      through 30-day follow up. No coronary perforation or pericardial tamponade
      occurred. CONCLUSIONS: The CROSSER system is a safe device that can cross many
      occlusions after a conventional guidewire failure. With additional refinement and
      improvements to the device, this success rate could be further increased.

PMID- 16598104
TI  - Use of the TandemHeart percutaneous ventricular assist device to support patients
      undergoing high-risk percutaneous coronary intervention.
AB  - OBJECTIVES: We describe our experience in using the TandemHeart percutaneous
      ventricular assist device (pVAD) during high-risk percutaneous coronary
      intervention (PCI). BACKGROUND: Coronary artery bypass grafting (CABG) is the
      preferred treatment for disease in an unprotected left main coronary artery or
      left main equivalent. However, severe comorbidities may preclude surgery in some
      patients. In these cases, PCI is also often a high-risk procedure. The pVAD is
      designed to provide circulatory support during high-risk PCI. METHODS AND
      RESULTS: We used the pVAD for hemodynamic support during PCI in 5 consecutive
      patients who were ineligible for CABG because of severe comorbidities. In all 5
      cases, the device was inserted and support initiated without complications.
      Percutaneous revascularization was successfully performed with pVAD support
      (approximately 3 L per minute). Four patients were supported for an average of
      107 minutes, the pVAD being withdrawn shortly after PCI; all 4 patients recovered
      uneventfully. The fifth patient required support for 48 more hours after the
      procedure because of poor ventricular function. He died of heart failure and
      severe mitral regurgitation 10 days after pVAD withdrawal. CONCLUSIONS: The pVAD
      may provide sufficient circulatory support for hemodynamic protection during high
      risk PCI, thus improving morbidity and mortality and broadening the therapeutic
      options for high-risk patients. Further investigation of this device is
      warranted.

PMID- 16598105
TI  - The evolving role for a left ventricular assist device in high-risk percutaneous
      coronary interventions.

PMID- 16598106
TI  - Impact of diabetes on five-year outcomes after vein graft interventions performed
      prior to the drug-eluting stent era.
AB  - OBJECTIVE: The aim of this study was to evaluate the differences in 5-year
      outcomes among diabetic and nondiabetic patients undergoing saphenous vein graft
      (SVG) percutaneous coronary intervention (PCI) prior to the era of distal
      protection and drug-eluting stents. BACKGROUND: PCI of native coronary arteries
      is known to be associated with higher rates of adverse outcomes in diabetic
      patients compared to nondiabetic patients. However, the impact of diabetes on
      long-term outcomes after SVG interventions is not as well established. We
      conducted an evaluation of 5-year outcomes after SVG PCI in the two decades prior
      to the availability of distal protection devices and drug-eluting stents.
      METHODS: Data on 2,556 subjects (1,780 nondiabetic and 776 diabetic) undergoing
      SVG PCI at Emory Hospital from 1981 to 2001 were collected and entered into a
      computerized database and analyzed for adverse cardiovascular outcomes. RESULTS:
      Compared to the nondiabetic group, the diabetic group had worse 1-year (87.7% vs.
      94.9%; p < 0.0001) and 5-year survival rates (62.9% vs. 78.5%; p < 0.0001). In
      the subset of patients receiving stents, 5-year survival remained significantly
      worse in the diabetic group (78.2% vs. 87.1%; p = 0.009). After multivariate
      analysis, diabetes was an independent predictor of 5-year mortality (hazard ratio
      = 1.8; 95% CI = 1.5-2.5; p < 0.0001). CONCLUSION: Diabetic patients undergoing
      vein graft PCI prior to the distal protection and drug-eluting stent era had
      significantly worse long-term outcomes compared to nondiabetic patients. The
      effect on long-term outcomes using these newer devices in diabetic subjects
      undergoing SVG PCI must be established for a true assessment of their impact.

PMID- 16598107
TI  - Rapid ambulation after coronary angiography via femoral artery access: a
      prospective study of 1,000 patients.
AB  - OBJECTIVE: The aim of this study was to assess the safety and efficacy of a 90
      minute bed rest protocol for patients undergoing elective 6 Fr coronary
      angiography via the femoral artery. BACKGROUND: Following cardiac
      catheterization, reducing the period of immobilization has beneficial effects on
      patient comfort. Previously, immobilization times of up to 2 hours have been
      shown to be safe. METHODS: One-thousand consecutive patients undergoing elective
      daytime coronary angiography were studied. We used a novel protocol with a
      commercially available compression device to mobilize patients after only 90
      minutes of bed rest. RESULTS: Of 1,000 patients, 1 had a minor bleed that was
      successfully treated with manual pressure followed by a pressure dressing. Two
      patients developed pseudoaneurysms, 1 of whom required a transfusion. No other
      patients required a transfusion or experienced hemodynamic instability. Thirteen
      patients had delayed discharge, most commonly due to a delay in obtaining
      ultrasound scans to exclude pseudoaneurysm. CONCLUSION: Our results demonstrate
      that early mobilization (90 minutes) is feasible and safe for patients undergoing
      elective coronary angiography performed via the right femoral artery.

PMID- 16598108
TI  - You can't keep a good man (or woman) down.

PMID- 16598109
TI  - Drug-eluting stent strut distribution: a comparison between Cypher and Taxus by
      optical coherence tomography.
AB  - OBJECTIVES: The purpose of this study is to compare the stent strut distribution
      between Cypher and Taxus stents by using optical coherence tomography (OCT) in a
      phantom model. BACKGROUND: Previous studies demonstrated that the distribution of
      stent struts might affect amount of neointima proliferation after drug-eluting
      stent (DES) implantation. METHODS: We developed experimental models made of
      silicon tubing angled at 0 degrees, 30 degrees, and 60 degrees. Testing was
      performed on two types of stents, Cypher and Taxus, which represent current FDA
      approved DES. After deployment, OCT was performed and measurements were obtained
      as follows at two cross sections; maximum and minimum numbers of visualized stent
      strut sites: (1) number of visualized stent struts; (2) angle between stent
      struts (interstrut angle); (3) mean interstrut angle; (4) the delta mean angle
      was defined as the margin between each value of the interstrut angle and mean
      interstrut angle. RESULTS: In the Cypher stent, both the interstrut angle and the
      delta mean angle were significantly better than all other stents evaluated (all
      comparisons between stents; p < 0.05, respectively). CONCLUSIONS: The present
      study found that the stent strut distribution of two stents, Cypher and Taxus,
      which represent current FDA-approved drug-eluting systems, were significantly
      different and suggested that the Cypher stent maintained a more regular strut
      distribution despite expansion in various anatomical situations, and therefore
      would provide the most regular and predictable drug delivery.

PMID- 16598110
TI  - The influence of body mass index on outcomes and the benefit of antiplatelet
      therapy following percutaneous coronary intervention.
AB  - In general, obesity is associated with better outcome in patients undergoing
      percutaneous coronary interventions (PCI). One small study has suggested that
      these patients do not achieve adequate platelet inhibition with clopidogrel and
      that this may shape clinical outcomes. We evaluated the relationship between body
      mass index (BMI) and clinical outcomes at 1 year following PCI in patients
      randomized to clopidogrel or placebo in the CREDO trial. METHODS AND RESULTS:
      BMI, baseline clinical characteristics and clopidogrel regimen were assessed in
      2,116 patients. The primary study endpoint was the 1-year composite of death, MI
      or stroke. A total of 342 patients had low or normal BMI (< 25 kg per m2), 847
      were overweight (25-29.9 kg per m2), 810 were obese (30-39.9 kg per m2) and 113
      were very obese (greater than or equal to 40 kg per m2). Obese patients were more
      likely to be young males with diabetes, hypertension and hyperlipidemia (p <
      0.01). Bleeding complications occurred in 38% of low BMI, 32% of
      overweight/obese, and 25% of very obese patients (p = 0.03). Randomization to
      clopidogrel was associated with a 25% risk reduction in 1-year death, MI or
      stroke events, as BMI increased by every 5 kg per m2 (p = 0.009). CONCLUSION: In
      general, increasing BMI was associated with better efficacy and bleeding outcomes
      at 1 year in this nonurgent PCI population. Randomization to early- and long-term
      clopidogrel was associated with even further improvements in those with
      increasing BMI.

PMID- 16598111
TI  - Transitioning from heparin to bivalirudin in patients undergoing ad hoc
      transradial interventional procedures: a pilot study.
AB  - OBJECTIVE: The present study evaluated the combined use of unfractionated heparin
      (UFH) and bivalirudin during ad hoc transradial interventional procedures.
      BACKGROUND: As a result of its proven efficacy in recent clinical trials, the
      direct thrombin inhibitor bivalirudin is now increasingly utilized as the
      anticoagulant of choice for coronary interventions. However, it is currently not
      packaged for diagnostic procedures. Patients undergoing ad hoc transradial
      procedures thus need unfractionated heparin during the diagnostic catheterization
      to protect against radial occlusion. It is unclear how the transition to
      bivalirudin should be undertaken if a subsequent intervention were performed.
      METHODS: A total of 117 patients underwent ad hoc transradial procedures. Fifty
      one patients underwent diagnostic catheterizations receiving only 5,000 Units of
      UFH in divided doses: (1) Group 1H (n = 26), 2,500 U after sheath insertion and
      2,500 U at conclusion; (2) Group 2H (n = 25), 1,000 U followed by 4,000 U. Sixty
      six patients subsequently underwent interventions as part of the same procedure
      and received standard bivalirudin (B) dosing in addition to the initial UHF dose:
      Group 1B (n = 40), 2,500 Units of UFH plus B; Group 2B (n = 26), 1,000 Units of
      UFH plus B. The primary endpoint was postprocedure radial occlusion; secondary
      endpoints were any major adverse cardiac event (MACE) and any bleeding
      complication. RESULTS: One patient (1%) had postprocedure radial occlusion, but
      this recanalized at 1 month. There were no deaths, and urgent target lesion
      revascularization was not required. Non-Q wave myocardial infarction occurred in
      7.5%, all in Group 1B. No bleeding complications occurred. CONCLUSIONS: The
      administration of bivalirudin after a reduced heparin dose in patients undergoing
      ad hoc transradial interventional procedures was not associated with adverse
      events in this small pilot study.

PMID- 16598112
TI  - Use of bivalirudin as the foundation anticoagulant during percutaneous peripheral
      interventions.
AB  - OBJECTIVE: The objective of this retrospective chart review was to evaluate the
      safety and feasibility of using the direct thrombin inhibitor bivalirudin as the
      procedural anticoagulant in patients undergoing percutaneous peripheral
      intervention (PPI). BACKGROUND: Patients with peripheral artery disease are in
      general a high-risk population that requires safe and reliable anticoagulation
      with complete thrombin inhibition. Bivalirudin, a direct thrombin inhibitor, has
      been shown to be as effective as heparin, but with fewer bleeding events in PCI
      trials, and recent data suggest that bivalirudin may provide the same benefits in
      PPI. METHODS: This was a retrospective chart review of patients who underwent PPI
      with bivalirudin as the foundation anticoagulant. Bivalirudin was administered as
      a 0.75 mg per kg bolus, followed by a 1.75 mg per kg per hour infusion for the
      duration of the procedure. The primary endpoint was procedural success defined as
      residual stenosis less than or equal to 20%. Ischemic and hemorrhagic events were
      collected, as well as time-to-sheath removal, ambulation and discharge. RESULTS:
      Data were collected for 150 patients. Procedural success was achieved in 98.5%.
      Ischemic events were low: death (2.0%), myocardial infarction (0.0%), urgent
      revascularization (0.8%). Major and minor hemorrhage occurred in 4.7% and 2.0% of
      patients, respectively. Time-to-sheath removal, ambulation and discharge were
      short. CONCLUSION: Bivalirudin provided effective anticoagulation in these
      generally high-risk patients undergoing PPI. Ischemic and bleeding events were
      low and comparable to those reported in the literature, suggesting that
      bivalirudin is safe to use in this population.

PMID- 16598113
TI  - Initial experiences of removal of intra-aortic balloon pumps with the Angio-Seal.
AB  - Angio-Seal, a vascular hemostasis device, has been shown to be safe and effective
      in rapidly achieving hemostasis after cardiac catheterization or coronary
      intervention. We propose that similar results can be obtained with Angio-Seal
      when removing an intra-aortic balloon pump (IABP). We studied 16 patients in whom
      Angio-Seal was utilized in IABP removals. The primary safety endpoint was a
      composite of major complications such as retroperitoneal bleeding, vessel
      occlusion, loss of distal pulses, vascular surgery or death, and minor
      complications such as hematoma (> 10 cm), AV fistula or pseudoaneurysm by 7 days
      after removal. The time-to-hemostasis was 2-5 minutes (mean 3.3 minutes). There
      were no instances of major or minor complications by the seventh day in any
      patients.

PMID- 16598114
TI  - Iron heart.

PMID- 16598115
TI  - Simultaneous papillary muscle avulsion and free wall rupture during acute
      myocardial infarction. Intra-aortic balloon pump: a bridge to survival.
AB  - Mechanical complications of acute myocardial infarction (AMI) are rare, but often
      fatal. Medical therapy does not provide adequate risk reduction, and surgical
      correction is recommended when feasible. Supplemental hemodynamic support
      utilizing intra-aortic counterpulsation with a balloon pump provides an
      improvement in morbidity and mortality when combined with a corrective surgical
      approach. We report a case of an elderly male with a progressive 2-week history
      of ischemic symptoms presenting with acute pulmonary edema, hypotension and an
      inferior wall ST-elevation MI. His hospital course was complicated by ischemic
      mitral regurgitation (MR) and cardiogenic shock, which resulted in a papillary
      muscle rupture/avulsion from the inferolateral myocardial wall, and a
      communication for blood from ventricle to pericardial space. Initial management
      included mechanical ventilation, pharmacologic inotropic support, percutaneous
      revascularization of the culprit lesion and intra-aortic balloon
      counterpulsation. The patient underwent further successful cardiovascular
      surgical correction of his incompetent mitral valve, free wall rupture and other
      obstructive coronary arteries, leading to discharge and survival. Mechanical
      complications from AMI and the role of intra-aortic balloon support are
      discussed.

PMID- 16598116
TI  - One-dimensional structure of catena-poly[tetraethylammonium [tetracyanoiron(III)
      mu-cyano-[bis(ethylenediamine)cadmium(II)]-mu-cyano] tetrahydrate].

PMID- 16598117
TI  - Two new non-centrosymmetric lithium salts of glycine: bis(glycine) lithium
      chromate monohydrate and bis(glycine) lithium molybdate.

PMID- 16598118
TI  - Poly[tetraaquadi-mu3-malonato-cobalt(II)calcium(II)].

PMID- 16598119
TI  - The first salt of an isolated pentachloroplumbate(II) trianion.

PMID- 16598120
TI  - Facial pi...Cl...pi interactions as the directing motif of the supramolecular
      structures of Mg2+ and Ca2+ bis[hydrotris(pyrazolyl)borate] chloroform
      disolvates.

PMID- 16598121
TI  - Dichloro(propane-1,3-diamine-kappa2N,N')platinum(II), dichloro(propane-1,3
      diamine-kappa2N,N')palladium(II) and mu-4,9-diazadodecane-1,12-diamine
      kappa2N1,N4:kappa2N9,N12-bis[dichloroplatinum(II)].

PMID- 16598122
TI  - Clathrate solvates of tetrakis(4-methoxycarbonylphenyl)porphyrin and its zinc(II)
      pyridine complex, in which the porphyrin host structures are stabilized by
      porphyrin-porphyrin stacking and C-H...O attractions.

PMID- 16598123
TI  - Strontium diibuprofenate dihydrate, strontium malonate sesquihydrate, strontium
      diascorbate dihydrate and strontium 2-oxidobenzoate hydrate at 120 K.

PMID- 16598124
TI  - Poly[[aquacopper(II)]-mu-adamantane-1,3-diacetato].

PMID- 16598125
TI  - An indium(III)-water chain based on an unusual acyclic water pentamer.

PMID- 16598126
TI  - Poly[piperazinium2+ [hexa-mu-hydrogen phosphito-mu-piperazine-pentazinc(II)]].

PMID- 16598127
TI  - Bis(2,2'-bipyridine)iodo(oxo)tri-mu3-sulfido-tricopper(I)tungsten(VI).

PMID- 16598128
TI  - 5,7,7,12,14,14-Hexamethyl-4,11-diaza-1,8-diazoniacyclotetradecane
      pentacyanonitrosoferrate(II) dihydrate: a supramolecular compound constructed by
      hydrogen bonds.

PMID- 16598129
TI  - Poly[[[diaquadioxouranium(VI)]-mu3-nitriliotriacetato-kappa3O:O':O'']
      trihydrate].

PMID- 16598130
TI  - Oxalate complexes of the (eta6-p-cymene)ruthenium(II) fragment: mu-oxalato
      kappa2O1,O2:kappa2O1',O2'-bis[(eta6-p-cymene)(triphenylphosphine-kappaP)
      ruthenium(II)] bis(tetrafluoroborate) and (eta6-p-cymene)(oxalato
      kappa2O,O')(pyridine-3,5-dicarboxylic acid-kappaN)ruthenium(II).

PMID- 16598131
TI  - 1,8,14,20-Tetraoxa-11,23-dithiatricyclo[21.3.0.0(9,13)]hexacosa-9,12,21,24
      tetraene.

PMID- 16598133
TI  - 2,2'-isopropylidenediphenol.

PMID- 16598132
TI  - Neutron diffraction studies of the 1:1 and 2:1 cocrystals of benzene-1,2,4,5
      tetracarboxylic acid and 4,4'-bipyridine.

PMID- 16598134
TI  - Simple hydrogen-bonded chains in 2,2'-bipyridinium thiocyanate, hydrogen-bonded
      chains of rings in 2,2'-bipyridinium picrate and hydrogen-bonded sheets in 2,2'
      bipyridinium hydrogensulfate.

PMID- 16598135
TI  - N,N'-Bis(2-chloronicotinoyl)-N-(3-nitrophenyl)hydrazine monohydrate: complex
      sheets built from O-H...N, N-H...O and C-H...O hydrogen bonds.

PMID- 16598136
TI  - (Z)-4-(2,6-Dichlorophenyldiazenyl)-6-{[1,3-dihydroxy-2-(hydroxymethyl)propan-2
      ylamino]methylene}-2-methoxycyclohexa-2,4-dienone and the 3-methoxyphenyldiazenyl
      and 4-methoxyphenyldiazenyl analogues.

PMID- 16598137
TI  - C[triple-bond]C-H systems as hydrogen-bond donors and acceptors: trans-1,2
      diethynylcyclohexane-1,2-diol and trans-1,4-diprop-2-ynylcyclohexane-1,4-diol
      monohydrate.

PMID- 16598138
TI  - Strychninium N-phthaloyl-beta-alaninate N-phthaloyl-beta-alanine and brucinium N
      phthaloyl-beta-alaninate 5.67-hydrate.

PMID- 16598139
TI  - 7-Amino-2,5-dimethylpyrazolo[1,5-a]pyrimidine hemihydrate redetermined at 120 K:
      a three-dimensional hydrogen-bonded framework.

PMID- 16598140
TI  - N-Phenyl-N'-pyridylureas: stereochemical basis for anticonvulsant activity.

PMID- 16598141
TI  - 1,3-Dimethylisoguanine.

PMID- 16598142
TI  - (4S)-3-[(2R,3S)-3-Hydroxy-2-methyl-3-phenylpropionyl]-4-isopropyloxazolidin-2
      one.

PMID- 16598143
TI  - anti-2-Hydroxy-2-methyl-1-tetralone oxime: X-ray and density functional theory
      study.

PMID- 16598144
TI  - Two pseudopolymorphic hydrates of brucine: brucine-water (1/4) and brucine-water
      (1/5.25) at 130 K.

PMID- 16598145
TI  - (-)-(5S,8S,9R,10S,13R,14R)-15,16-Dideoxy-16,17-epoxy-16-oxospongian-15-yl
      acetate.

PMID- 16598146
TI  - Four cycloalkanespiro-4'-imidazolidine-2',5'-dithiones.

PMID- 16598147
TI  - (3-Hydroxy-2-pyridylmethyl)dimethylammonium dihydrogenphosphate.

PMID- 16598148
TI  - Cinnamolid-3beta-ol hemihydrate and 3beta-hydroxycinnamolide acetate, two
      drimanolide-class sesquiterpene lactones from Warburgia ugandensis.

PMID- 16598149
TI  - Hydrogen-bonded framework structures in 4-[(4-chloro-3
      nitrobenzoyl)hydrazinocarbonyl]pyridinium chloride and N-3,5-dinitrobenzoyl-N'
      isonicotinoylhydrazine.

PMID- 16598150
TI  - Cocrystals of diastereoisomers of 1,4-dihydropyridine derivatives.

PMID- 16598151
TI  - 4-Amino-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-fluoro-7H-pyrrolo[2,3
      d]pyrimidine: a bis-fluorinated analogue of 2'-deoxytubercidin.

PMID- 16598152
TI  - Di-tert-butyl ketone hydrazone and di-tert-butyl ketone
      triphenylphosphoranylidenehydrazone.

PMID- 16598153
TI  - Botulinum neurotoxins: perspective on their existence and as polyproteins
      harboring viral proteases.

PMID- 16598155
TI  - Searching for bacteriocin-producing lactic acid bacteria in soil.
AB  - A survey was conducted on the isolation and characterization of bacteriocin
      producing lactic acid bacteria in soil. Forty-two acid-producing bacterial
      strains were isolated from 55 soil samples collected in Yamanashi prefecture,
      Japan. Investigation of antibacterial activities of isolates revealed that three
      isolates, Lactobacillus animalis C060203, Enterococcus durans C102901 and
      Leuconostoc mesenteroides subsp. mesenteroides C060204, showed antibacterial
      activities against the indicator strain of Lactobacillus sakei JCM 1157T.
      Bacteriocin from Enterococcus durans C102901 showed different characteristics
      from the known durancin L28-1A, produced by Enterococcus durans L28-1.
      Furthermore, this is the first report of a bacteriocin being produced by
      Lactobacillus animalis. Viewing from the species, bacteriocins from strains
      C102901 and C060203 showed high possibilities for the novel substances. These
      significant findings suggest that soil may be a common source for the isolation
      of novel bacteriocin-producing lactic acid bacteria.

PMID- 16598154
TI  - Amino acid substitutions in malate dehydrogenases of piezophilic bacteria
      isolated from intestinal contents of deep-sea fishes retrieved from the abyssal
      zone.
AB  - To examine the occurrence in other deep-sea bacteria of two amino acid
      substitutions (Ala-180 and His-229) in malate dehydrogenase (MDH) found
      previously in the deep-sea piezophilic Moritella sp. strain 2D2, we cloned and
      sequenced MDH genes of deep-sea piezophilic Moritella and Shewanella strains
      isolated from intestinal contents of deep-sea fishes, as well as other Moritella
      species from deep-sea water and sediments: M. marina, M. japonica, and M.
      yayanosii. The piezophilic Moritella strains had a Val residue or an Ala residue
      at position 180 and all the Moritella strains except for one had a His residue at
      position 229. However, four piezophilic-strain-specific substitutions at
      positions 103, 111, 229, and 283 were found to be completely conserved in the MDH
      of the intestinal Moritella strains of deep-sea fishes, indicating the
      substitutions may be habitat-specific. The piezophilic Shewanella strains had a
      Val residue and a Gln residue at positions 180 and 229, respectively. However,
      the MDHs of the Shewanella strains had five piezophilic-strain-specific
      substitutions at positions 61, 65, 107, 161, and 202. Therefore, the enzymatic
      strategies for responding to deep-sea high pressure environments of the MDHs
      between the genera Moritella and Shewanella are potentially different. Moreover,
      homology modeling shows these substitutions found in the MDHs of both genera
      except for position 229 in the subunit interface are located on the exposed
      region of the MDH molecules, indicating the substitutions may be related to the
      hydration state of the molecules.

PMID- 16598156
TI  - Trans fatty acids promote the growth of some Lactobacillus strains.
AB  - Five Lactobacillus strains (2 L. gasseri, 2 L. plantarum and 1 L. reuteri) were
      cultured in modified MRS medium containing fatty acids (FAs) instead of Tween 80
      for 24 h at 37 degrees C, to learn the effect of saturated and unsaturated FAs on
      the Lactobacillus growth. Free FAs included palmitic (16:0), palmitoleic (c9
      16:1), stearic (18:0), oleic (c9-18:1), elaidic (t9-18:1), cis-vaccenic (c11
      18:1), vaccenic (t11-18:1), linoleic (c9, c12-18:2), conjugated linoleic (c9, t11
      and t10, c12-18:2), alpha-linolenic (c9, c12, c15-18:3), alpha-eleostearic (c9,
      t11, t13-18:3), eicosapentaenoic (20:5), and docosahexaenoic (22:6) acids. Among
      free FAs, oleic acid stimulated the growth of all Lactobacillus strains, whereas
      palmitoleic acid had almost no affect on the Lactobacillus growth. Saturated FAs
      such as stearic and palmitic acids inhibited or did not affect the Lactobacillus
      growth. Polyunsaturated FAs such as alpha-linolenic, eicosapentaenoic and
      docosahexaenoic acids strongly inhibited the Lactobacillus growth at 7.6 x 10(-4)
      m. Octadecenoic acids such as oleic, elaidic, cis-vaccenic and vaccenic acids
      remarkably promoted the growth of L. gasseri, regardless of the different double
      bond positions and configurations. When oleic or cis-vaccenic acid was incubated
      with L. gasseri, the FAs was transformed to cyclopropane FAs
      (methyleneoctadecanoic acids) after incorporation into the cells. On the other
      hand, trans FAs such as elaidic and vaccenic acids incorporated into the cells
      were not converted to another FAs. Conjugated linoleic and alpha-eleostearic
      acids having a trans double bond promoted the Lactobacillus growth. The growth of
      L. gasseri was also stimulated by trans-rich free FAs from hydrogenated canola
      and fish oils. These results showed that octadecenoic acid and trans FAs had
      strong promotion activities for the Lactobacillus growth due to their
      incorporation into membrane lipids.

PMID- 16598157
TI  - Phylogenetic relationship within the Erythrobasidium clade: molecular
      phylogenies, secondary structure, and intron positions inferred from partial
      sequences of ribosomal RNA and elongation factor-1alpha genes.
AB  - Phylogenetic relationships within the Erythrobasidium clade as a lineage of the
      urediniomycetous yeasts were examined using partial regions of 18S rDNA, 5.8S
      rDNA, 26S rDNA, internal transcribed spacers (ITSs), and elongation factor (EF)
      1alpha. Combined data analysis of all segments successfully yielded a reliable
      phylogeny and confirmed the cohesion of species characterized by Q-10(H2) as a
      major ubiquinone. Differences in secondary structure predicted for a variable
      region in 26S rDNA corresponded to major divergences in the phylogenetic tree
      based on the primary sequence. The common presence of a shortened helix in this
      region was considered to be evidence of monophyly for species with Q-10(H2),
      Sakaguchia dacryoides, Rhodotorula lactosa, and Rhodotorula lamellibrachiae,
      although it was not as strongly supported by the combined data tree. The
      information on intron positions in the EF-1alpha gene had potential usefulness in
      the phylogenetic inference between closely related species.

PMID- 16598158
TI  - Comparison of the microbial diversity in cold-seep sediments from different
      depths in the Nankai Trough.
AB  - We have investigated the molecular phylogeny of cold-seep sediments obtained from
      the Nankai Trough, at depths of about 600, 2,000, and 3,300 m, and compared the
      microbial diversity profiles of those sediments samples. The gamma-Proteobacteria
      that might function as sulfide oxidizers and the symbiotically related delta
      Proteobacteria which might function as sulfate reducers were identified amongst
      the bacteria from all depths of the sediments. However, anoxic methane oxidizing
      archaea (ANME) and methanogens were only found in the 600 m deep sediments. These
      results indicated that the cold-seep microbial sulfur circulation system could be
      functioning in the shallow seep sediment at a depth of 600 m and the microbial
      activities at these sites might be more dynamic than at other deeper cold-seep
      sites.

PMID- 16598159
TI  - Identification of strains assigned to the genus Asaia Yamada et al. 2000 based on
      restriction analysis of 16S-23S rDNA internal transcribed spacer regions.

PMID- 16598160
TI  - Immuno-magnetic separation and agar layer methods for the isolation of freeze
      injured Yersinia enterocolitica O:8 from water.
AB  - To develop an effective method to isolate an injured pathogenic Yersinia
      enterocolitica O:8 organism from environmental samples, we compared the isolation
      of freeze-injured and non-injured Y. enterocolitica O:8 and found that the
      isolation was more successful when immuno-magnetic separation (IMS) with anti-Y.
      enterocolitica O:8 antibody was used. Plating onto cefsulodin-irgasan-novobiocin
      (CIN) agar and Virulent Yersinia enterocolitica (VYE) agar by means of the agar
      layer method was found to be effective in isolating the injured cells. The alkali
      treatment which is generally used for selective detection of Yersinia organism
      failed to isolate freeze-injured pathogenic Y. enterocolitica O:8 cells. Recovery
      methods without using the alkali treatment were superior for detecting freeze
      injured Y. enterocolitica O:8. Our results demonstrate that the IMS and the agar
      layer methods should be used to isolate injured pathogenic Yersinia organisms
      from environmental samples such as water.

PMID- 16598161
TI  - Macromorphometric study on ciliary body location in canine eyes.
AB  - This macroscopic study firstly examined the precise locational information of the
      canine ciliary body, i.e., the ciliary crown and the ciliary ring in the beagle.
      The safe and effective transscleral laser photocoagulation technique requires the
      accurate location of the ciliary body. In both sides of the eyeball in 10 beagle
      dogs, the width of the ciliary ring and the distance from the limbus to the
      ciliary ring were measured with calipers using a stereomicroscope at the 8
      points. The widest portion of ciliary body was found at the dorsal to ventro
      temporal area of the lateral canthus (lateral portion of the eyelid; ear side).
      In contrast, the narrowest portion was seen at the ventro-nasal to nasal area of
      the medial canthus (medial portion of the eyelid; nasal quadrants). Use of
      transscleral photocoagulation at the present narrowest area of ciliary body may
      carry a high risk of destruction of the optic portion of retina.

PMID- 16598163
TI  - Effect of intermittent administration of sustained release isosorbide dinitrate
      (sr-ISDN) in rats with pressure-overload heart.
AB  - Recent studies have demonstrated the benefits of nitric oxide (NO) on myocardial
      hypertrophy and myocardial fibrosis. It was suggested that NO has a protective
      effect on myocardial cell through the neurohormonal system. This effect serves to
      highlight the important role of NO in maintaining the function and form of heart
      with chronic heart failure. However, there are no known reports about on the
      effect of prolonged administration of nitrate on pressure over-load heart. This
      study was conducted to examine the long-term effect of oral nitrate therapy in
      rats with pressure-overloaded heart. An abdominal aorta constricted (AC) model of
      pressure-overloaded heart was created in male Wistar rats. Sustained release
      isosorbide dinitrate (sr-ISDN) (5 mg/kg once a daily) was administered to the
      rats once a daily for 12 weeks. The animals were euthanized during the study
      period, and the heart was collected and weighed. Histopathological examination
      was performed to evaluate the effect of sr-ISDN on myocardial hypertrophy and
      fibrosis. The ratio of heart to body weight increased significantly in AC rat and
      this increase was significantly prevented by sr-ISDN treatment. Histopathological
      examination showed significant increase in fibrotic area of AC rat compared to
      sham rat, this increase was inhibited by sr-ISDN treatment. Cardiomyocyte
      transverse diameter was significantly increased in AC rat compared with sham rat,
      but this increase tended to decrease by sr-ISDN treatment. In conclusion,
      intermittent administration with sr-ISDN has mild effect in inhibiting cardiac
      hypertrophy and marked effect in inhibiting fibrosis due to pressure-overload.

PMID- 16598162
TI  - Effect of combination therapy with lactoferrin and antibiotics against
      staphylococcal mastitis on drying cows.
AB  - We examined combination therapy with both lactoferrin (Lf) and antibiotics on
      clinical mastitis due to Staphylococcus aureus (S.aureus) on drying cows. The
      clinical symptoms of mastitic quarters were cured 81% of combination therapeutic
      quarters at 7 days post injection (dpi). Moreover, most of mammary gland
      secretions (MGSs) in combination therapeutic quarters were normal at 7 days after
      parturition. In the quarters with combination therapy, S.aureus counts, Lf
      concentrations and content rate of concanavalin A (Con A) low-affinity Lf
      decreased and were lower than in the quarters treated with Lf or antibiotics
      alone. The mRNA expression of tumor necrosis factor alpha (TNFalpha) of the
      quarters with combination therapy also decreased and was lower than that of the
      Lf or antibiotics treated. The mRNA expression of pro-inflammatory cytokines and
      chemokines in bovine mammary gland epithelial lined cells (BMEC) stimulated with
      Lf were lower than those of Con A low-affinity Lf stimulated BMEC. Moreover, Lf
      showed an inhibitory effect to the induction of pro-inflammatory cytokine mRNA
      expression when co-stimulated with Lf and Con A low-affinity Lf. Nuclear factor
      kappa B (NFkappaB) activation was also induced with Con A low-affinity Lf, and
      the inhibitory effects of Lf were also confirmed on BMEC co-stimulated with Lf
      and Con A low-affinity Lf. These results indicated that the efficacy of
      combination therapy with antibiotics and Lf caused antibacterial effect of
      antibiotics and inhibition of pro-inflammatory cytokine and chemokine production
      with Lf via the inhibition of NFkappaB activation.

PMID- 16598164
TI  - Effects of sugar cane extract on pseudorabies virus challenge of pigs.
AB  - This experiment aimed to evaluate the efficacy of sugar cane extract (SCE) on the
      modulation of porcine immunity against pseudorabies virus (PrV) infection. Twelve
      week-old experimental pigs were fed with SCE (500 mg/kg of body weight per day)
      for 3 days and challenged with PrV (2 x 10(5) TCID(50)) on the second day. Pigs
      that were only challenged with PrV and without SCE-treatment served as controls.
      The leukocyte functional assays were performed on the 7th and 14th day post-PrV
      challenge. Our results showed a significant enhancement (P<0.05) of natural
      killer cytotoxicity, lymphocyte proliferation, phagocytic function of monocytes,
      and interferon-gamma (IFN-gamma) production of CD4(+) and gammadelta T cells in
      the SCE-treated pigs compared with the controls. In addition, SCE administration
      reduced the severity of clinical signs and brain lesion in the course of disease
      in PrV-challenged pigs. SCE-treated pigs showed a 12% growth enhancement compared
      with untreated controls. SCE administration had an immunostimulating effect on
      porcine immunity that may subsequently enhance protective activities against PrV
      infection which may be extensively applied in field for the prevention of
      infections.

PMID- 16598165
TI  - Effect of Angiotensin II Type 1 receptor blocker on cardiac angiotensin
      converting enzyme and chymase-like activities, and cardiac fibrosis in
      cardiomyopathic hamsters.
AB  - It has been reported that cardiac chymase has an effect on cardiac fibrosis
      through the Angiotensin (Ang) II formation and an Ang II-independent mechanism.
      In the present study, Ang II type 1 (AT1) receptor blocker (candesartan
      cilexetil) was administered to dilated cardiomyopathic (DCM; Bio TO2) hamsters
      for 4 weeks to study the effect of AT1 receptor blocker on cardiac chymase-like
      activity and cardiac fibrosis. Echocardiography, histological examination, and
      assessment of cardiac angiotensin-converting enzyme (ACE)/chymase-like activities
      were conducted. Hamsters showed cardiac dysfunction due to increased left
      ventricular dimensions and decreased ventricular wall thickness, significant
      increase in cardiac chymase-like activity, and fibrosis. This result indicates
      that the cardiac chymase-like activity is responsible for cardiac fibrosis. When
      candesartan cilexetil was administered to Bio TO2 hamsters, cardiac chymase-like
      activity increased significantly, whereas cardiac fibrosis decreased
      significantly. Cardiac ACE and chymase-like activities were unchanged in non-DCM
      hamsters with candesartan cilexetil. This suggests that the cardiac Ang II
      formation mechanism was stimulated by suppressing the effect of cardiac Ang II,
      and cardiac chymase-like activity could be increased. Moreover, this mechanism
      may be more highly activated if cardiac Ang II is activated in the heart. In
      conclusion, we demonstrated that AT1 receptor blocker reduced cardiac fibrosis,
      although cardiac chymase-like activity increased. Because the Ang II-forming
      pathway and the effect of chymase in hamsters is similar to that in dogs, the
      results of the present study may supplement the available information for dogs.

PMID- 16598166
TI  - Histopathological characteristics of Ito cells and Kupffer cells in the feline
      liver.
AB  - The histopathological characteristics of Ito cells and Kupffer cells were
      investigated in the liver of 21 cats (age range: 6 months -18 years) autopsied in
      our laboratory during 2003. Immunohistochemical examinations were performed using
      antibodies against lysozyme, desmin and alpha-smooth muscle actin. No Kupffer
      cells reacted with the antibody against lysozyme. However, macrophages in the
      lung and spleen showed a positive reaction with the antibody. This finding
      suggests a possibility that the amount of lysozyme in the Kupffer cells of feline
      liver is comparatively small. On the other hand, large vacuole-laden cells were
      observed in the hepatic perisinusoid of some feline cases, and these cells showed
      a positive reaction with antibodies against desmin and alpha-smooth muscle actin.
      These cells could be Ito cells with large lipid vacuoles. This conclusion was
      supported by electron microscopic observation and oil red O staining. However, no
      such large vacuole-laden perisinusoidal cells were detected in the liver of young
      cats less than 2 years old. The present study revealed the histopathological
      features of Kupffer cells and Ito cells in the feline liver.

PMID- 16598167
TI  - Diurnal variations of blood pressure in cats.
AB  - Blood pressure (BP) was analyzed invasively using the telemetry system in
      unanesthetized, unrestrained healthy adult mongrel cats. After surgical
      implantation of a telemetry transmitter, BP was transiently elevated due to the
      invasive nature of the surgery, but it was gradually decreased. BP was largely
      stabilized seven to ten days postsurgery. Once BP was settled, systolic,
      diastolic and mean BPs(2) were obtained at 5-min intervals in individual cats.
      Hourly averages of these BP values revealed a diurnal variation with two peaks at
      8:00 and 19:00. We also found that BP was significantly higher when cats were
      active compared to when they were sleeping or at rest (p<0.05). The average 24-hr
      BP in 20 healthy cats was 118.4+/-11.0 (systolic), 78.0+/-8.7 (diastolic) and
      94.8+/-9.5 mmHg (mean) by the telemetry system.

PMID- 16598168
TI  - Molecular typing of VapA-positive Rhodococcus equi isolates from Jeju native
      horses, Korea.
AB  - We recently demonstrated the presence of virulence-associated protein antigen
      (VapA)-positive Rhodococcus equi in Jeju Island, Korea. These bacteria contained
      one of two distinct plasmid types, a 90-kb type II plasmid, which has been found
      in isolates from the native Kiso horses of Japan, and a new variant, a 90-kb type
      V plasmid. However, the genotypic characters of the VapA-positive R. equi from
      Jeju native horses and their environments are poorly understood. Ninety-eight
      isolates from soil samples and 89 isolates from fecal samples were collected from
      five farms that breed or have bred Jeju native horses, and were tested for the
      presence of VapA by immunoblotting and PCR. Of the 98 soil isolates and 89 fecal
      isolates, seven and 13 were VapA-positive R. equi, respectively. In 2003, two
      Jeju foals died suddenly and were brought to the Faculty of Veterinary Medicine,
      Cheju National University, for postmortem examination. Pure cultures of R. equi
      were isolated from the lung lesions of both foals. Of the 16 clinical isolates,
      14 were VapA-positive R. equi. Of the 34 VapA-positive clinical and environmental
      isolates, 16 contained the 90-kb type II plasmid and 18 contained a 90-kb type V
      plasmid. Pulsed-field gel electrophoresis (PFGE) patterns of the VapA-positive
      isolates from Jeju horses and Kiso horses, containing the 90-kb type II plasmid,
      were compared and formed two distinct groups. Furthermore, 18 virulent isolates
      containing the 90-kb type V plasmid formed two distinct PFGE groups (of 16 and
      two isolates). These results demonstrate that two virulence plasmid types are
      widespread in R. equi in Jeju native horses. However, there is little diversity
      in the PFGE patterns of virulent isolates, suggesting the clonal spread of
      virulent R. equi. The PFGE pattern of the virulent R. equi isolates from Jeju
      native horses in Korea is not identical to those of Kiso native horses in Japan.

PMID- 16598169
TI  - Identification of herds with cattle persistently infected with bovine viral
      diarrhea virus by virological evaluation of three calves.
AB  - For the identification of herds with cattle persistently infected (PI) with
      bovine viral diarrhea virus, 1,272 animals from 20 herds were subjected to serum
      neutralizing (SN) test using the Nose strain and virus isolation. Eighteen PI
      cattle were detected from 5 herds. On the phylogenetic tree based on the
      nucleotide sequences of the 5' untranslated region, the isolates from the PI
      cattle were classified into genotypes-1a or -1b. Of 3 unvaccinated calves aged 6
      to 12 months selected from each herd, the probabilities of obtaining 2 or more
      non-PI cattle with SN antibody titers of 64 or more (P(SN)), one or more PI
      cattle (P(VI)), and either of the conditions (P(Total)) were calculated using the
      hypergeometric probability model. P(Total) for the 5 herds with PI cattle was
      1.000. P(SN) for 3 herds with many PI cattle within the selected age group was as
      low as 0.500 or less, and P(VI) was as high as 0.886 or more. P(SN) in the 2
      other herds with few PI cattle was 1.000, and P(VI) was as low as 0.375 or less.
      P(Total) in 13 of 15 herds without PI cattle was 0.000, and was 0.714 or 0.774
      for the 2 other herds. These results suggest that herds with PI cattle can be
      predicted with high accuracy when both SN test and virus isolation are performed
      on only 3 unvaccinated calves aged 6 to 12 months selected from a herd.

PMID- 16598170
TI  - Cerebral metabolism in brains of rats infected with neuropathogenic murine
      leukemia viruses.
AB  - Friend murine leukemia virus A8 and PVC211 cause spongiform neurodegeneration in
      rat brains. Glutamate is an important neurotransmitter synthesized from alpha
      ketoglutaric acid, an intermediate product of the citric acid cycle, and
      glutamine is synthesized from glutamate. To examine the brain metabolism of rats
      infected with neuropathogenic viruses, the amount of glutamate and glutamine in
      the brains of rats infected with A8, PVC211, and non-neuropathogenic 57 was
      measured using high performance liquid chromatography, and the (13)C-label
      incorporation into the C4 position of glutamate and glutamine from [1-(13)C]
      glucose was measured with (13)C nuclear magnetic resonance. In the cerebral
      hemisphere and region containing the brain stem and basal ganglia of rats
      infected with A8 and PVC211 at 8-9 weeks post-infection (wpi), the amount of
      glutamine was decreased compared with the 57-infected rats. The amount of
      glutamate was decreased in the cerebral hemisphere of the A8-infected rats and
      the region containing the brain stem and basal ganglia of PVC211-infected rats at
      8-9 wpi. The amount of [4-(13)C] glutamine and [4-(13)C] glutamate in the
      cerebral hemisphere and region containing the brain stem and basal ganglia of
      rats infected with A8 and PVC211 at 8-9 wpi was equivalent to that of the 57
      infected rats. These results suggest that in the brains of rats infected with
      neuropathogenic viruses, de novo synthesis of glutamate and glutamine is not
      decreased, but the ability to maintain quantitative levels of glutamate and
      glutamine is decreased compared with the brains of rats infected with non
      neuropathogenic virus.

PMID- 16598171
TI  - The effects of one-time hoof trimming on blood biochemical composition, milk
      yield, and milk composition in dairy cows.
AB  - Although not scientifically proven, hoof trimming has been empirically shown to
      increase milk yields in healthy dairy cows. In this study, we examined the effect
      of one-time hoof trimming on blood biochemical composition, milk yield, and milk
      composition in healthy dairy cows. Eleven cows in the mid to late lactation
      period that were clinically fit and without hoof disease were subjected to hoof
      trimming, and metabolic profile tests and dairy herd improving tests were
      performed before and three weeks after the hoof trimming. The metabolic profiles
      showed changes in albumin, blood urea nitrogen, ammonia, glucose, and beta
      hydroxybutyric acid as a result of the hoof trimming. This was indicated by the
      fact that the cows began to intake more roughage after hoof trimming than prior
      to hoof trimming, and rumen fermentation became stable. There was no change in
      milk yield after trimming. However, the milk fat and milk protein compositions
      were significantly increased after trimming.

PMID- 16598172
TI  - Cardiac remodeling and angiotensin II-forming enzyme activity of the left
      ventricle in hamsters with chronic pressure overload induced by ascending aortic
      stenosis.
AB  - Cardiac remodeling and angiotensin II-forming enzyme activity of the left
      ventricle on chronic pressure overload were studied in male Syrian hamsters,
      whose chymase activity is similar to that of dogs. Pressure overload was achieved
      by banding at the ascending aorta (aortic stenosis). Echocardiography,
      histological analysis, and analysis of cardiac angiotensin-converting enzyme and
      chymase-like activities were performed. At 10 weeks after banding, concentric
      hypertrophy of the left ventricle was evident. At 20 weeks after banding, the
      ventricular weight-to-body ratio, cardiac fibrosis, and cardiac chymase-like
      activity were significantly increased, while cardiac angiotensin-converting
      enzyme activity was significantly decreased. This suggests that cardiac chymase,
      compared with cardiac angiotensin-converting enzyme, was activated against the
      chronic pressure overload and was responsible for the cardiac remodeling through
      the formation of angiotensin II. Considering the utility of the rodents, the
      interspecies similarity of the Ang II-forming pathway, and the effect of chymase
      in the hamsters, the present model is considered useful for studies evaluating
      the effect of Ang II and chymase in the canine heart with chronic pressure
      overload.

PMID- 16598174
TI  - Cryptosporidium infection in juvenile pet rabbits.
AB  - Cryptosporidium infection was confirmed by fecal examination for the first time
      in pet rabbits in a wholesale store located in Kanagawa Prefecture, Japan. Fecal
      samples were obtained postmortem from juvenile rabbits (n=66), which had died
      after developing diarrhea. Feces from healthy rabbits (n=30) were also collected
      and examined as controls. Two types of Cryptosporidium oocysts distinctive in
      size and shape were found (Type A and B). Types A and B oocysts were detected
      from 16.7% and 13.6% of the diarrheic, and 3.3% and 0% of the normal feces,
      respectively. Since Cryptosporidium oocysts were detected at a higher rate in the
      diarrheic rabbits than in the healthy rabbits, special caution should be taken
      when handling a pet rabbit presenting with diarrhea.

PMID- 16598173
TI  - Estrogen modulates Bcl-2 family proteins in ischemic brain injury.
AB  - Estradiol acts as a neuroprotective factor against brain injury. This study
      investigated whether estradiol modulates the Bcl-2 family proteins in ischemic
      brain injury. Adult female rats were ovariectomized and treated with estradiol
      prior to middle cerebral artery occlusion (MCAO). Brains were collected 24 hr
      after MCAO, and infarct volumes were analyzed. Estradiol significantly reduces
      the infarct volume and decreases the positive cells of TUNEL staining in cerebral
      cortex. In ischemic cerebral cortex, the level of Bcl-2 was decreased, and the
      level of Bax was significantly increased. Estradiol prevents the injury-induced
      decrease of Bcl-2 and increase of Bax. In conclusion, our findings suggest that
      estradiol plays a potent protective role in brain injury through the regulation
      of Bcl-2 family proteins.

PMID- 16598175
TI  - A case of feline sporotrichosis.
AB  - We excised surgically a feline granulomatous lesion and performed
      histopathological, mycological and molecular examinations. As a result, it was
      diagnosed as sporotrichosis, which was the second recorded case of a cat so
      afflicted in Japan. After the operation, we recognized another nodule on the
      lymph node. Histopathological examination was therefore performed, but no fungi
      were detected. To prevent recurrence, the cat was administered a antimycotic
      drug, itraconazole. As a result, no recurrence was found. Excision of the lesion
      is the treatment of choice for feline sporotrichosis.

PMID- 16598176
TI  - High field (4.7 T) magnetic resonance imaging of feline hip joints.
AB  - Magnetic resonance imaging (MRI) is a non-invasive technique widely used to
      investigate degenerative joint disease (DJD). In this study, we obtained magnetic
      resonance images of feline hip joints, using a high magnetic field MRI unit (4.7
      tesla) with proton density (PD)-weighted and T2-weighted fast spin-echo (FSE). PD
      weighted FSE provided detailed anatomical images of feline hip joints with superb
      depiction of subchondral bones of the femoral head and acetabulum. Articular
      cartilage (AC) was also visualized with PD-weighted and T2-weighted FSE; however,
      mild AC lesions noted on gross examination were not detectable with these
      sequences.

PMID- 16598177
TI  - Pathogenicity of fowl adenovirus isolated from gizzard erosions to immuno
      suppressed chickens.
AB  - Pathogenicity of a fowl adenovirus (FAV), JM1/1 strain of serotype 1 derived from
      gizzard erosions of a broiler chicken, was examined to specific pathogen-free
      (SPF) chickens pre-treated with infectious bursal disease viruses (IBDVs) or
      cyclophosphamide (CY). Virulent IBDVs, classical type, were inoculated orally at
      3 days of age of SPF chickens. CY was treated subcutaneously for 3 days after
      hatch. FAV was given orally at 30 days of age. At 40 days of age, all chickens
      were bled and autopsied for serology and gross observation. Gizzard lesions were
      ranked by the scores depending on their severities. IBDV- or CY-treated chickens
      showed significantly higher gizzard lesion scores than non treated birds. There
      were no gross lesions in any other organs except for bursal atrophy.
      Serologically, antibody production against FAV was highly suppressed by IBDV
      infection or CY treatment.

PMID- 16598178
TI  - Isolation and genetic analysis of Japanese encephalitis virus from a diseased
      horse in Japan.
AB  - Japanese encephalitis (JE) developed in an unvaccinated half-bred horse kept in
      Tottori Prefecture, Japan. The animal showed ataxia with pyrexia and low
      appetite, and ultimately died. A viral strain was isolated from the cerebrum of
      the horse and was identified as JE virus (JEV) by RT-PCR using JEV specific
      primers. The isolated JEV was classified into genotype I by nucleotide sequence
      analysis of the viral envelope gene. We believe that this is the first report of
      the genotype I strain being isolated from a horse.

PMID- 16598179
TI  - Cloning of the feline GADD45 cDNA and analysis of its mutation in feline lymphoma
      cell lines.
AB  - Growth arrest and DNA damage-inducible protein 45 (GADD45) plays an important
      role in suppressing multistep carcinogenesis. In this report, we describe the
      isolation of the complete wild-type feline GADD45 cDNA from feline tissues.
      Expression of feline GADD45 mRNA was detected in the liver, spleen, kidney, lung,
      and testis. The predicted amino acid sequences encoded by the full-length feline
      GADD45 cDNA display sequence homology with those from other vertebrates, and as
      in the case of human GADD45, cell growth suppression was observed by ectopic
      expression of feline GADD45. However, no mutations were detected by sequence
      analysis of feline GADD45 in several feline lymphoma cell lines, indicating that
      the GADD45 mutation might be uncommon in feline oncogenesis.

PMID- 16598180
TI  - Resin tag length of one-step and self-etching adhesives bonded to unground
      enamel.
AB  - Length of resin tags yielded by utilization of an one-step conventional adhesive
      system and self-etching adhesive system on unground enamel was observed. In study
      Groups I and III, the enamel surface was etched for 60 seconds with 35%
      phosphoric acid gel and adhesive systems PQ1 (Ultradent Products, Inc) and Adper
      Prompt L Pop (3M/ESPE) were applied. Adper Prompt L Pop (3M/ESPE) was also
      applied in Group II in accordance with the manufacturer's recommendations. After
      application of these adhesive systems to dental enamel, specimens were prepared
      for light microscopy analysis to ascertain degree of penetration (x400). The
      results were submitted to an analysis of variance at the 5% level; whenever there
      was significance, the Tukey test was applied at the 5% level. It was found that
      acid etching prior to application of conventional and self-etching adhesive
      materials provided higher penetration of the adhesive into the unground enamel
      surface compared to that achieved solely by application of self-etching adhesive.

PMID- 16598181
TI  - Anxiety may enhance pain during dental treatment.
AB  - The purpose of this study was to clarify the effects of anxiety about dental
      treatment on pain during treatment. Subjects consisted of 57 consenting sixth
      grade students at Tokyo Dental College (male: 32, female: 25), all of whom
      participated in this study during their clinical training program. They knew how
      third molars were extracted and all had experience of assisting in tooth
      extraction. Prior to the study, trait anxiety in the subjects was evaluated
      according to the State-Trait Anxiety Inventory (STAI, Japanese version). The
      students were asked to read one of two scenarios describing a scene in which a
      third molar was extracted while imagining themselves to be the patient. Scene 1
      is set in an "environment where the patient feels safe and comfortable," and the
      Scene 2 is set in an "environment where the patient feels strong anxiety". The
      subjects were asked to imagine the anxiety and pain in that scenario and evaluate
      that pain according to a visual analogue scale (VAS). Two scenarios were randomly
      shown to the subjects in a crossover manner. No significant correlation between
      trait anxiety and preoperative anxiety was observed. There was no difference in
      level of preoperative anxiety for Scene 1 and Scene 2 between the high- and low
      trait anxiety groups. This suggests that there was no relationship between
      sensitivity to anxiety as a characteristic of the subject and amplitude of
      anxiety immediately prior to treatment. Scene 2 elicited significantly higher
      anxiety before injection of regional anesthesia, significantly higher pain during
      insertion of the needle, and significantly higher pain during extraction of the
      tooth than Scene 1. This difference suggests that patients feel stronger pain if
      anxiety in the treatment environment is high and that it is, therefore, important
      to reduce anxiety during treatment to reduce pain.

PMID- 16598182
TI  - Changes in orthodontic cephalometric reference points on application of
      orthopedic force to jaw: three-dimensional finite element analysis.
AB  - The present study investigated the effects of two orthodontic appliances on
      changes in the cephalometric reference planes using the three-dimensional finite
      element method. We simulated the use of a headgear and an orthopedic facial mask,
      two devices for the application of orthodontic force to the jaw. Using a finite
      element model of the skull, orthodontic force was applied to the maxillary first
      molar in a posterior or anterior direction. Changes in the maxilla, mandible and
      cephalometric reference planes were ascertained by the three-dimensional finite
      element method. The results showed that posterior force caused a slight posterior
      displacement and clockwise rotation of the reference planes, while anterior force
      caused anterior displacement and counterclockwise rotation. Since the maxilla was
      displaced and rotated in the same direction, the degrees of cephalometric
      displacement and rotation of the maxilla were smaller than the actual values.

PMID- 16598183
TI  - Model surgery technique for Le Fort I osteotomy--alteration in occlusal plane
      associated with upward transposition of posterior maxilla.
AB  - It is difficult to translate analytical values into accurate model surgery by
      traditional methods, especially when moving the posterior maxilla. This is
      because cephalometric radiographic analysis generated information on movement of
      the posterior nasal spine (PNS) can not be recreated in model surgery. Therefore,
      we propose a method that accurately reflects such analysis and simulation of
      movement using Quick Ceph 2000 (Orthodontic Processing Corporation, USA). This
      will allow the enrichment of model surgery prior to actual surgery in cases where
      upward movement of the posterior maxilla is involved. All patients who
      participated in this study had skeletal mandibular prognathism characterized by a
      small occlusal plane angle in respect to the S-N plane. Cephalometric radiographs
      were taken and analyzed with the Quick Ceph 2000. Pre- and post-surgical
      evaluations were performed using Sassouni arc analysis and Ricketts analysis.
      Prior to transposition, we then prepared an anterior occlusal bite record on a
      model mounted on an articulator. This bite was then used as a reference when the
      molar parts were to be transposed upwards. The use of a occlusal bite permitted
      an accurate translation of the preoperative computer simulation into model
      surgery, thus facilitating favorable surgical results.

PMID- 16598184
TI  - Variation of biocontaminant levels within and between homes--the AIRALLERG study.
AB  - Few epidemiological studies report on reliability of exposure measurements even
      though this significantly influences the results of correlation and regression
      analysis often used in these studies. Poor reliability of exposure measurement
      reduces the ability to detect a true association between a certain component and
      health outcome variables. The aim of this study was to determine the ratio of the
      within-home and between-home components of variance of a number of
      biocontaminants measured in house dust in the framework of an international study
      conducted in the Netherlands, Germany and Sweden (the AIRALLERG study). To this
      end, duplicate dust samples were collected from children's beds and from living
      room floors in over 100 homes. Samples were taken at the same point in time.
      Variables considered were the dust mass collected in mg/m2 and the concentrations
      of the house dust mite allergens Der p 1 and Der f 1, cat allergen Fel d 1,
      endotoxin, (1 --> 3)-beta-D-glucan and extracellular polysaccharides, all per
      gram of dust and per square meter of sampling surface. An analysis of variance
      showed that the within-home variance was small compared to the between-home
      variance for most variables (mostly less than half) with the exception of glucan
      on mattresses, when expressed in mug/g. Investigation of variation over time is
      needed for a more complete assessment of the use of these variables in
      epidemiological analyses of exposure-response relationships.

PMID- 16598185
TI  - CCL19 reduces tumour burden in a model of advanced lung cancer.
AB  - Epstein-Barr virus-induced molecule 1 ligand chemokine (CCL19) is a CC chemokine
      that chemoattracts both dendritic cells (DC) and T lymphocytes. We evaluated the
      antitumour efficacy of CCL19 in a murine model of spontaneous bronchoalveolar
      cell carcinoma. These transgenic mice (CC-10 TAg) express the SV40 large T
      antigen under the Clara Cell promoter, develop bilateral, multifocal, pulmonary
      carcinomas and die at 4 months owing to progressive pulmonary tumour burden. To
      mimic therapy in late-stage disease, 3-month-old transgenic mice were treated
      with recombinant CCL19 (0.5 microg dose(-1)) by intranodal (axillary lymph node
      region) injection three times per week for 4 weeks. CCL19 treatment led to a
      marked reduction in tumour burden with extensive mononuclear infiltration of the
      tumours compared to diluent treated controls. Flow cytometric analyses showed
      significant increases in CD4 and CD8T cell subsets as well as DC in the lungs of
      CCL19-treated mice. Lung tissue cytokine profiles showed a shift towards immune
      stimulatory molecules with a decrease in the immunosuppressive cytokine TGF-beta.
      Our findings show that CCL19 may serve as a potential immune stimulator and
      provide a strong rationale for the evaluation of CCL19 in cancer immunotherapy.

PMID- 16598186
TI  - Cyclin L1 (CCNL1) gene alterations in human head and neck squamous cell
      carcinoma.
AB  - We evaluated the expression and amplification of cyclin L1 (CCNL1) gene, a
      potential oncogene localised in the commonly amplified 3q25-28 region, in human
      head and neck squamous cell carcinomas (HNSCCs). Overexpression was observed in
      55 out of 96 cases (57%) and amplification in nine out of 35 tumours (26%) with
      no relationships to the clinico-pathological parameters. The Cyclin L1 antibody
      we developed labels nuclear speckles in tumour cells compatible with a role for
      CCNL1 in RNA splicing.

PMID- 16598189
TI  - Male biased sex ratio in the Mediterranean fruit fly Ceratitis capitata, an
      example of Y-chromosome meiotic drive.
AB  - A case of Y-chromosome meiotic drive is reported in the Mediterranean fruit fly
      Ceratitis capitata. It arose in an irradiated male and results in excess of
      males. Male excess is inherited strictly from father to son. A Y-linked factor MP
      (male producer) is proposed. Higher drive can be selected, but distortion
      declines rapidly in the absence of selection. Hybrid males from crosses between
      driving males and nondriving females also show drive but to a reduced extent,
      suggesting the action of suppressors. Sex ratio distortion is independent of
      postzygotic mortality, and is not associated with an obvious chromosome
      arrangement. Spermiogenesis in driving males is characterised by abnormalities in
      sperm tails and reduced numbers in some sperm cysts, whereas neighbouring cysts
      of the same MP testis are essentially wild type. The average number of missing
      sperms plus deformed sperms approximates to the average depression in female
      recovery among the progenies of siblings, suggesting that most of the missing or
      abnormal sperms would have given rise to females, that is, they would have been X
      bearing. To explain the heterogeneity between neighbouring cysts, a theory is
      proposed that links it to variation in X-chromosome sensitivity to MP, arising by
      random suppression of the genetic basis of sensitivity during the six mitotic
      divisions in the origin of the cyst from its stem cell before meiosis.

PMID- 16598187
TI  - Significance of the metastasis-inducing protein AGR2 for outcome in hormonally
      treated breast cancer patients.
AB  - The anterior gradient protein-2 (AGR2) is inducible by oestrogen and itself can
      induce metastasis in a rat model for breast cancer. Here, a rabbit antibody to
      recombinant human AGR2 was used to assess its prognostic significance in a
      retrospective cohort of 351 breast cancer patients treated by adjuvant hormonal
      therapy. The antibody stains 66% of breast carcinomas to varying degrees. The
      percentage of positive carcinoma cells in tumours directly correlates with the
      level of AGR2 mRNA (Spearman's rank correlation, P = 0.0007) and protein (linear
      regression analysis r2 = 0.95, P = 0.0002). There is a significant association of
      staining of carcinomas for AGR2 with oestrogen receptor alpha (ERalpha) staining
      and with low histological grade (both Fisher's Exact test P<0.0001). In the
      ERalpha-positive cases, but not the ERalpha-negative cases, when subdivided into
      the separate staining classes for AGR2, there is a significantly progressive
      decrease in patient survival with increased staining (log rank test, P = 0.006).
      The significant association of staining for AGR2 with patient death over a 10
      year period (log rank test P = 0.007, hazard ratio = 3) only becomes significant
      at 6 years of follow-up. This may be due to the cessation of adjuvant hormonal
      therapy at an earlier time, resulting in adverse re-expression of the metastasis
      inducing protein AGR2.

PMID- 16598190
TI  - Genealogy of the nuclear beta-fibrinogen locus in a highly structured lizard
      species: comparison with mtDNA and evidence for intragenic recombination in the
      hybrid zone.
AB  - The study of nuclear genealogies in natural populations of nonmodel organisms is
      expected to provide novel insights into the evolutionary history of populations,
      especially when developed in the framework of well-established mtDNA
      phylogeographical scenarios. In the Iberian Peninsula, the endemic Schreiber's
      green lizard Lacerta schreiberi exhibits two highly divergent and allopatric
      mtDNA lineages that started to split during the late Pliocene. In this work, we
      performed a fine-scale analysis of the putative mtDNA contact zone together with
      a global analysis of the patterns of variation observed at the nuclear beta
      fibrinogen intron 7 (beta-fibint7). Using a combination of DNA sequencing with
      single-strand conformational polymorphism (SSCP) analysis, we show that the
      observed genealogy at the beta-fibint7 locus reveals extensive admixture between
      two formerly isolated lizard populations while the two mtDNA lineages remain
      essentially allopatric. In addition, a private beta-fibint7 haplotype detected in
      the single population where both mtDNA lineages were found in sympatry is
      probably the result of intragenic recombination between the two more common and
      divergent beta-fibint7 haplotypes. Our results suggest that the progressive
      incorporation of nuclear genealogies in investigating the ancient demography and
      admixture dynamics of divergent genomes will be necessary to obtain a more
      comprehensive picture of the evolutionary history of organisms.

PMID- 16598191
TI  - Genetic constraints on floral evolution: a review and evaluation of patterns.
AB  - The characteristics of flowers influence most aspects of angiosperm reproduction,
      including the agents of pollination and patterns of mating. Thus, a clear view of
      the forces that mediate floral phenotypic evolution is central to understanding
      angiosperm diversity. Here, we inform on the capacity for floral phenotype to
      respond to selection by reviewing published data on heritabilities and genetic
      correlations for several classes of floral traits (primary sexual, attraction,
      mating system) in hermaphroditic plants. We find significant heritability for all
      floral traits but also variation among them, as well as a tendency for
      heritability to vary with mating system, but not life history. We additionally
      test predictions stemming from life history theory (eg, negative covariation
      between male-female traits and flower size-flower number), and ideas concerning
      the extent and pattern of genetic integration between flowers and leaves, and
      between the sexes of dioecious and gynodioecious species. We find mixed evidence
      for life history tradeoffs. We find strong support for floral integration and its
      relation with floral morphology (actinomorphy vs zygomorphy) and for a decoupling
      of floral and vegetative traits, but no evidence that modular integration varies
      with floral morphology. Lastly, we find mixed evidence for a relationship between
      the level of sexual dimorphism in attraction traits and the between-sex
      correlation in gender dimorphic plants.

PMID- 16598192
TI  - Effects of expectancy and abstinence on the neural response to smoking cues in
      cigarette smokers: an fMRI study.
AB  - Cues associated with drug taking can trigger relapse, drug seeking, and craving
      in addicted individuals. Behavioral studies suggest that drug availability and
      withdrawal can affect the individual response to drug cues. Moreover, the
      importance of subjective craving in cue-induced relapse has been questioned and
      an alternative model put forward according to which drug cues trigger habitual
      drug-seeking behaviors independently of craving. We used functional magnetic
      resonance imaging to compare the brain response to smoking and control videotapes
      in 20 healthy smokers, while varying their expectancy to smoke and abstinence
      levels. The neural response to cigarette cues was strongly modulated by
      expectancy and, to a lesser extent, abstinence. In people expecting to smoke
      immediately after the scan, smoking cues activated brain areas implicated in
      arousal, attention, and cognitive control. However, when subjects knew they would
      not be allowed to smoke for 4 h, there was almost no brain activation in response
      to smoking cues, despite equivalent reported levels of craving. In the
      dorsolateral prefrontal cortex, the neural response was a function of both
      craving and expectancy. Thalamo-cingulate connectivity, thought to be an index of
      arousal, was greater during expectancy than nonexpectancy. Our findings confirm
      the importance of expectancy in the neural response to drug cues, and lend
      support to the theory that these cues act on brain areas involved in arousal and
      attention.

PMID- 16598193
TI  - Transforming growth factor-beta 1 stimulates angiotensinogen gene expression in
      kidney proximal tubular cells.
AB  - The present study investigated whether transforming growth factor-beta 1 (TGF
      beta1) exerts an autocrine positive effect on angiotensinogen (ANG) gene
      expression in rat kidney proximal tubular cells, and delineates its underlying
      mechanism(s) of action. Rat immortalized renal proximal tubular cells (IRPTCs)
      and freshly isolated mouse renal proximal tubules were incubated in the absence
      or presence of active human TGF-beta1. IRPTCs were also stably transfected with
      rat TGF-beta1 or p53 tumor suppressor protein (p53) cDNA in sense (S) and
      antisense (AS) orientations. ANG mRNA and p53 protein expression were assessed by
      reverse transcription-polymerase chain reaction and Western blotting,
      respectively. Reactive oxygen species (ROS) generation was quantified by
      lucigenin assay. Active TGF-beta1 evoked ROS generation and stimulated ANG mRNA
      and p53 protein expression, whereas a superoxide scavenger and inhibitors of
      nicotinamide adenine dinucleotide oxidase and p38 mitogen-activated protein
      kinase (p38 MAPK) abolished the TGF-beta1 effect. Stable transfer of p53 cDNA (S)
      enhanced and p53 cDNA (AS) abolished the stimulatory effect of TGF-beta1 on ANG
      mRNA expression in IRPTCs. Our results demonstrate that TGF-beta1 stimulates ANG
      gene expression and its action is mediated, at least in part, via ROS generation,
      p38 MAPK activation, and p53 expression, suggesting that angiotensin II and TGF
      beta1 may form a positive feedback loop to enhance their respective gene
      expression, leading to renal injury.

PMID- 16598194
TI  - Unearthing uric acid: an ancient factor with recently found significance in renal
      and cardiovascular disease.
AB  - Uric acid is strongly associated with cardiovascular and renal disease, but is
      usually not considered to have a causal role. However, recent experimental,
      epidemiological, and clinical studies provocatively suggest that uric acid may
      contribute to the development of hypertension, metabolic syndrome, and kidney
      disease in some patients. Clinical studies are urgently needed to examine this
      important possibility.

PMID- 16598195
TI  - CRIT is expressed on podocytes in normal human kidney and upregulated in
      membranous nephropathy.
AB  - Complement C2 receptor inhibitor trispanning (CRIT) is a novel human complement
      regulatory cell surface receptor. It binds the human complement protein C2 and
      blocks the classical pathway of complement activation, thus protecting the cell
      against complement attack. CRIT expression in the kidney was analyzed by
      immunohistochemistry and in situ hybridization. Normal kidney and renal biopsies
      of patients with different nephropathies were studied. In glomeruli, CRIT protein
      was expressed only in podocytes. CRIT was also detected in endothelial cells of
      arterioles and arteries, but not of veins and peritubular and glomerular
      capillaries. A homogeneous and marked upregulation of CRIT was observed in
      podocytes in membranous nephropathy (MN). In focal and segmental
      glomerulosclerosis (FSGS) and minimal change disease, CRIT was downregulated in
      glomeruli with a loss of the staining in sclerotic lesions of FSGS. No specific
      changes were observed in the other nephropathies studied. However, podocytes
      showed in all pathologies a redistribution of CRIT in the cell bodies of
      'activated' podocytes. The intensity of mRNA transcription correlated directly
      with the protein staining in the normal kidney and in MN. These data indicate
      that CRIT is expressed in the normal human kidney essentially by glomerular
      podocytes and arterial endothelial cells. The podocyte CRIT expression is
      upregulated in MN, which is in strong contrast with the known loss of podocyte
      complement receptor 1. CRIT might represent the last line of defense against
      complement aggression in MN, and the upregulation of CRIT in 'activated'
      podocytes might represent a similar self-defense mechanism.

PMID- 16598196
TI  - Arachidonic acid induces ERK activation via Src SH2 domain association with the
      epidermal growth factor receptor.
AB  - Within the kidney, angiotensin II type 2 (AT(2)) receptor mediates phospholipase
      A(2) (PLA(2)) activation, arachidonic acid release, epidermal growth factor (EGF)
      receptor transactivation, and mitogen-activated protein kinase activation.
      Arachidonic acid mimics this transactivation by an undetermined mechanism. The
      role of c-Src in mediating angiotensin II and arachidonic acid signaling was
      determined by employing immunocomplex kinase assay, Western blotting analysis,
      and protein immunoblotting on co-precipitated EGF receptor (EGFR) proteins and
      agarose conjugates of glutathione S-transferase fusion proteins containing the c
      Src homology 2 (SH2) and SH3 domains. Angiotensin II induced extracellular signal
      regulated kinase (ERK) activation in primary cultures of rabbit proximal tubule
      cells via the activation of c-Src and association of the EGFR with the c-Src SH2
      domain, effects that were mimicked by arachidonic acid and its inactive analogue
      eicosatetraynoic acid. Inhibition of PLA(2) by mepacrine and methyl arachidonyl
      fluorophosphate, AT(2) receptor by PD123319, Src family kinases by, 1-(tert
      butyl)-3-(4-chlorophenyl)-4-aminopyrazolo[3,4-d] pyrimidine (PP2) and c-Src by
      overexpression of a dominant-negative mutant of c-Src abrogated these effects.
      However, inhibitors of arachidonic acid metabolic pathways did not block these
      effects. The present work provides a new and novel paradigm for transactivation
      of a kinase receptor linked to a fatty acid, which may apply to activation of a
      variety of phospholipases and accompanying arachidonic acid release.

PMID- 16598197
TI  - Delayed administration of darbepoetin or erythropoietin protects against ischemic
      acute renal injury and failure.
AB  - Administration of human recombinant erythropoietin (EPO) at time of acute
      ischemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial
      regeneration, and promotes renal functional recovery. The present study aimed to
      determine whether darbepoetin-alfa (DPO) exhibits comparable renoprotection to
      that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved,
      and whether delayed administration of EPO or DPO 6 h following IRI ameliorates
      renal dysfunction. The model of IRI involved bilateral renal artery occlusion for
      45 min in rats (N = 4 per group), followed by reperfusion for 1-7 days. Controls
      were sham-operated. Rats were treated at time of ischemia or sham operation (T0),
      or post-treated (6 h after the onset of reperfusion, T6) with EPO (5000 IU/kg),
      DPO (25 mug/kg), or appropriate vehicle by intraperitoneal injection. Renal
      function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were
      analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI
      animals (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.08 +/- 0.03
      mmol/l vs EPO-IRI 0.04 +/- 0.01 mmol/l, P = 0.01). Delayed administration of DPO
      or EPO (T6) also significantly abrogated subsequent renal dysfunction (serum
      creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.06 +/- 0.01 mmol/l vs EPO
      IRI 0.03 +/- 0.03 mmol/l, P = 0.01). There was also significantly decreased
      tissue injury (apoptosis, P < 0.05), decreased proapoptotic Bax, and increased
      regenerative capacity, especially in the outer stripe of the outer medulla, with
      DPO or EPO at T0 or T6. These results reaffirm the potential clinical application
      of DPO and EPO as novel renoprotective agents for patients at risk of ischemic
      acute renal failure or after having sustained an ischemic renal insult.

PMID- 16598198
TI  - Impaired fibrinolytic activity in type II diabetes: correlation with urinary
      albumin excretion and progression of renal disease.
AB  - Progression of renal disease and cardiovascular complications in type II diabetes
      mellitus have been shown to correlate with control of blood glucose, lipids,
      blood pressure, and smoking. These factors, however, do not appear to totally
      explain these diabetic complications. Renal disease and cardiovascular
      complications in type II diabetes are associated with vascular abnormalities and
      fibrosis, both of which may occur with impaired fibrinolysis. A cross-sectional
      study was therefore performed in 107 type II diabetic patients recruited from the
      Denver Metropolitan Area to examine the effect of impaired fibrinolysis, as
      assessed by the ratio of plasminogen activator inhibitor (PAI-1) to tissue-type
      plasminogen activator (t-PA). With urinary albumin excretion (UAE) as a risk
      factor for both renal disease progression and cardiovascular complications, the
      patients were analyzed with respect to UAE less than and greater than 1 gm/day.
      The age, blood glucose, hemoglobin A1C, duration of diabetes, lipids, body mass
      index, and smoking were no different between the groups. As expected, the group
      with greater UAE had worse renal function, the serum creatinine (1.98 +/- 0.24 vs
      1.21 +/- 0.05 mg/dl, P < 0.001) and creatinine clearance (55.5 +/- 6.0 vs 76.8 +/
      2.7 ml/min, P < 0.001) were significantly different. The type II diabetic
      patients with greater UAE exhibited significantly higher PAI-1/t-PA (2.43 +/-
      0.26 vs 1.85 +/- 0.07, P < 0.03). The past history of cardiac complications was
      also higher (87.5 vs 72.3%, P < 0.07) in the diabetic patients with more impaired
      fibrinolysis and greater UAE. Thus a prospective, randomized clinical trial in
      type II diabetes with PAI-1 inhibitors is needed.

PMID- 16598199
TI  - Turbulence of glomerular hemodynamics involved in progressive glomerulosclerosis.
AB  - There is increasing evidence that changes of glomerular hemodynamics or
      glomerular growth responses may promote the development of glomerulosclerosis.
      Major problems retarding research progress include lack of suitable experimental
      animal models, with the exception of the ablation model, and the need for in vivo
      real-time analysis of glomerular hemodynamics. This study examined the sequence
      of pathological changes from the viewpoints of microcirculation and
      histopathology, from the acute stage to the chronic course and the final stage of
      glomerulosclerosis, using the confocal laser scanning microscope system. There is
      a marked difference in prognosis between sham-operated (two-kidney) and
      nephrectomized (one-kidney) rats after injection with anti-Thy-1 antibody. The
      former reversibly returns to normal and the latter irreversibly go to progressive
      sclerosis, respectively. The turning point determining the progression of
      glomerulosclerosis in both groups seemed to be the period from 7 to 14 days after
      disease induction, when disturbance of local intraglomerular blood flow continued
      in the one-kidney groups. In conclusion, this study provides the first
      hemodynamic-based evidence showing that disturbance of intraglomerular
      microcirculation is a critical marker for progressive glomerulosclerosis.

PMID- 16598200
TI  - The AT2 gene may have a gender-specific effect on kidney function and pulse
      pressure in type I diabetic patients.
AB  - Diabetic nephropathy shows a higher incidence in male subjects, which may in part
      be owing to genetic factors. The angiotensin II type 2 receptor (AT2), present in
      the renal glomerulus, may oppose the deleterious effects of the type I receptor
      (AT1) through vasodilatation and growth inhibition. We determined whether the
      functional intronic G1675A or A1818T polymorphism of the X-chromosomal AT2 gene
      is associated with blood pressure levels or with kidney function. We genotyped
      996 (538 female/458 male subjects) Finnish patients with type I diabetes from the
      FinnDiane-study in a cross-sectional study. DNA samples were amplified using
      standard polymerase chain reaction protocol and the genotypes were determined by
      the minisequencing method. Male patients with the AA haplotype had a lower
      glomerular filtration rate (83 +/- 32 vs 94 +/- 34 ml min(-1) 1.73 m(-2), P =
      0.008) and a higher pulse pressure (PP) (62 +/- 18 vs 57 +/- 15 mm Hg, P = 0.002;
      P < 0.05 after adjustment for age) than did those with the GT haplotype. No
      differences between the genotypes or haplotypes and these variables were evident
      in females. In males, the G1675A was also an independent variable in a linear
      regression analysis with PP (r(2) = 0.16, coefficient=3.64, s.e.m.=1.38, P <
      0.01) as the dependent variable. These data suggest a gender-specific association
      between the AT2 gene and kidney function and premature aging of the arterial tree
      in patients with type I diabetes.

PMID- 16598201
TI  - Racial and ethnic differences in incident myocardial infarction in end-stage
      renal disease patients: The USRDS.
AB  - African Americans have a greater risk of cardiovascular disease (CVD) than
      Caucasians in early chronic kidney disease; however, limited data describe racial
      and ethnic differences in the risk of incident myocardial infarction (MI) among
      patients with end-stage renal disease (ESRD). We conducted a prospective,
      observational cohort study among 271 102 incident dialysis patients receiving
      renal replacement therapy enrolled in the United States Renal Data System (USRDS)
      for whom Medicare was the primary insurer between 1995 and 2000. The incidence
      and risk of any MI (non-fatal or fatal) estimated by Cox proportional hazards
      models was the primary outcome of interest. Of those with prevalent CVD at
      baseline (118 708), 14 849 had an incident non-fatal MI compared with 9926 events
      for those without prevalent CVD (152 394). Patients with prevalent CVD had higher
      crude rates of combined fatal and non-fatal MI (99.3/1000 person-years vs
      42.9/1000 person-years) compared with those without prevalent CVD. Among those
      with prevalent CVD, African Americans (adjusted relative risk (aRR)=0.65, 95%
      confidence interval (CI):0.62-0.68), Asian Americans (aRR=0.74, 95% CI: 0.66
      0.83), and Hispanics (aRR=0.72, 95% CI: 0.68-0.77) were 26-35% less likely to
      have an incident MI compared to Caucasians. Similarly, among those without
      prevalent CVD, racial/ethnic minorities were 26-42% less likely to have an
      incident MI compared to Caucasians. We conclude that in a national setting where
      comparable access to dialysis and associated medical care, exist, racial/ethnic
      minorities were found to have a lower risk of non-fatal and fatal MI than
      Caucasians.

PMID- 16598202
TI  - Peroxisome proliferator-activated receptor-gamma agonist is protective in
      podocyte injury-associated sclerosis.
AB  - We have previously observed increased expression of peroxisome proliferator
      activated receptor gamma (PPARgamma) in podocytes in both rat and human sclerotic
      conditions. The aim of the present study was to investigate whether activation of
      PPARgamma can attenuate podocyte injury-associated glomerulosclerosis in vivo.
      Puromycin aminonucleoside nephropathy was induced in Sprague-Dawley rats. The
      animals then either received no further treatment (control group (CONT)); or the
      PPARgamma agonist, pioglitazone (Pio) starting at week 0 (P0); or Pio starting at
      week 6 (P6), with sacrifice at week 12. At week 12, urinary protein excretion and
      systolic blood pressure were similar in the three groups. Glomerular filtration
      rate and glomerulosclerosis were decreased in CONT and P0 at week 12, but
      preserved in P6 rats. PPARgamma expression in CONT at 12 weeks was increased in
      podocytes and in mesangial WT-1 cells in segmentally sclerotic glomeruli, with
      less Wilms' tumor 1 (WT-1) staining. In P6 rats, mesangial WT-1 staining was
      lessened, but podocyte staining was strongly accentuated. Delayed treatment with
      Pio partially restored podocyte staining and tended to decrease the ratio of
      proliferating cell nuclear antigen-positive to apoptotic cells in glomeruli. Both
      treatment groups showed significantly reduced infiltrating glomerular macrophages
      and plasminogen activator inhibitor-1 mRNA expression in cortex, with no change
      in transforming growth factor-beta1 and tissue inhibitor of metalloproteinase-1
      mRNA. Pio also decreased renal cortical angiopoietin-like protein 4 expression to
      almost 20% of CONT group, associated with increased vascular endothelial-derived
      growth factor expression in glomeruli. We conclude that treatment with PPARgamma
      agonist has protective effects on progression of glomerulosclerosis.

PMID- 16598203
TI  - The predictive value of self-report scales compared with physician diagnosis of
      depression in hemodialysis patients.
AB  - The prevalence of depression in end-stage renal disease (ESRD) patients on
      hemodialysis has not been definitively determined. We examined the prevalence of
      depression and the sensitivity, specificity, positive, and negative likelihood
      ratios (+LR and -LR) of self-report scales using the physician-administered
      Structured Clinical Interview for Depression (SCID) as the comparison. Ninety
      eight consecutive patients completed the Beck Depression Inventory (BDI) and the
      Center for Epidemiological Study of Depression (CESD) scales. A physician blinded
      to BDI and CESD scores administered the SCID. Receiver/responder operating
      characteristic curves determined the best BDI and CESD cutoffs for depression.
      Depressed patients had more co-morbidities and lower quality of life, P<0.05. The
      prevalence of depression by SCID was 26.5% and of major depression was 17.3%. The
      CESD cutoff with the best diagnostic accuracy was 18, with sensitivity 69% (95%
      confidence interval (CI) (51%, 87%)), specificity 83% (95% CI (74%, 92%)),
      positive predictive value (PPV) 60%, negative predictive value (NPV) 88%, +LR
      4.14, and -LR 0.37. The best BDI cutoff was 14, with sensitivity 62% (95% CI
      (43%, 81%)), specificity 81% (95% CI (72%, 90%)), PPV 53%, NPV 85%, +LR 3.26, and
      -LR 0.47. Self-report scales have high +LR but low -LR for diagnosis of
      depression. When used for screening, the threshold for depression should be
      higher for ESRD compared with non-ESRD patients. Identifying depression using
      physician interview is important, given the low -LR of self-report scales.

PMID- 16598204
TI  - Body composition analysis with bioelectric impedance in adult Indians with ESRD:
      comparison with healthy population.
AB  - Evaluation of body composition provides clinically useful information in several
      diseases including chronic kidney disease. Bioimpedance analysis (BIA) is a
      simple, cheap, and noninvasive tool for monitoring body composition. We performed
      BIA in 451 healthy adults and 162 end-stage renal disease (ESRD) patients.
      Resistance (R) and reactance (Xc) values were obtained at 50-kHz frequency using
      a tetrapolar impedance meter. Body compartments were derived using population
      specific regression equations. Phase angles (arctan Xc/R) were calculated and
      impedance vector distribution was determined using the RXc graph method. Compared
      to healthy population, ESRD patients had similar post-dialysis resistance with
      lower reactance and phase angle, indicating decreased soft tissue mass and
      inadequate ultrafiltration. BIA equations estimated decreased fat mass index and
      intracellular water, whereas the total body and extracellular water percentages
      were increased. Sex-specific reference RXc plots with 95, 75, and 50% tolerance
      ellipses were drawn for the healthy population. A significant difference was
      noted in the vector positions and 95% confidence ellipses of the two sexes and
      body mass indices of </=25 and >25. In conclusion, we present the reference BIA
      parameters for Indian population. ESRD patients show significant body compartment
      alterations. The RXc score graph can differentiate ESRD patient from normal
      controls and can be used to monitor nutrition and hydration status.

PMID- 16598205
TI  - Outcomes in African Americans and Hispanics with lupus nephritis.
AB  - Poor outcomes have been reported in African Americans and Hispanics compared to
      Caucasians with lupus nephritis. The purpose of this retrospective analysis was
      to identify independent predictors of outcomes in African Americans and Hispanics
      with lupus nephritis. In total, 93 African Americans, 100 Hispanics, and 20
      Caucasians with a mean age of 28 +/- 13 years and an annual household income of
      32.9 +/- 17.3 (in 1000 US dollars) were studied. World Health Organization (WHO)
      lupus nephritis classes II, III, IV, and V were seen in 9, 13, 52, and 26%,
      respectively. Important baseline differences were higher mean arterial pressure
      (MAP) in African Americans compared to Hispanics and Caucasians (107 +/- 19, 102
      +/- 15, and 99 +/- 13 mmHg, P < 0.05), and higher serum creatinine (1.66 +/- 1.3,
      1.25 +/- 1.0, and 1.31 +/- 1.0 mg/dl, P < 0.025). African Americans had lower
      hematocrit compared to Hispanics and Caucasians (29 +/- 5, and 31 +/- 6, and 32
      +/- 7%, P < 0.05), and lower annual household income (30.8 +/- 14.9, 33.1 +/-
      15.9, and 42.2 +/- 29.3 in 1000 US dollars; P < 0.05). Lower prevalence of WHO
      class IV was seen in Caucasians (30%) compared to Hispanics (57%, P = 0.03) and
      African Americans (51%, P = 0.09). Development of doubling creatinine or end
      stage renal disease was higher in African Americans and Hispanics than in
      Caucasians (31, 18, and 10%; P < 0.05), as was the development of renal events or
      death (34, 20, and 10%; P < 0.025). Our results suggest that both biological
      factors indicating an aggressive disease and low household income are common in
      African Americans and Hispanics with lupus nephritis, and outcomes in these
      groups are worse than in Caucasians.

PMID- 16598206
TI  - Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating
      cells.
AB  - Recent advances have highlighted extensive phenotypic and functional similarities
      between normal stem cells and cancer stem cells. This raises the question of
      whether disease therapies can be developed that eliminate cancer stem cells
      without eliminating normal stem cells. Here we address this issue by
      conditionally deleting the Pten tumour suppressor gene in adult haematopoietic
      cells. This led to myeloproliferative disease within days and transplantable
      leukaemias within weeks. Pten deletion also promoted haematopoietic stem cell
      (HSC) proliferation. However, this led to HSC depletion via a cell-autonomous
      mechanism, preventing these cells from stably reconstituting irradiated mice. In
      contrast to leukaemia-initiating cells, HSCs were therefore unable to maintain
      themselves without Pten. These effects were mostly mediated by mTOR as they were
      inhibited by rapamycin. Rapamycin not only depleted leukaemia-initiating cells
      but also restored normal HSC function. Mechanistic differences between normal
      stem cells and cancer stem cells can thus be targeted to deplete cancer stem
      cells without damaging normal stem cells.

PMID- 16598208
TI  - Animal behaviour: chimpanzee choice and prosociality.
AB  - Silk et al. report that adult chimpanzees show no difference in their choices in
      a situation where one choice benefits a familiar conspecific and the other does
      not. From this, they conclude that chimpanzees are indifferent to the welfare of
      unrelated group members. But without additional data confirming that chimpanzees
      do choose differently in circumstances in which a difference would be expected,
      the authors cannot conclude that there is no difference in their scenario. How
      chimpanzees react to the welfare of unrelated group members remains an open
      question.

PMID- 16598212
TI  - Towards better biosecurity.

PMID- 16598213
TI  - Rightful owners.

PMID- 16598214
TI  - Shooting the messenger.

PMID- 16598216
TI  - Doubts over evolution block funding by Canadian agency.

PMID- 16598217
TI  - Further accusations rock Japanese RNA laboratory.

PMID- 16598219
TI  - Guinea experts cry foul on tribal exhibits.

PMID- 16598218
TI  - Korean science powerhouse sends Nobel laureate packing.

PMID- 16598220
TI  - Wellcome Trust fuelled bid to save British science treasure.

PMID- 16598221
TI  - Energy secretary ditches science advisers.

PMID- 16598222
TI  - From the front lines. H5N1 flu virus continues to sweep across the globe.

PMID- 16598226
TI  - Climate science: a sinking feeling.

PMID- 16598225
TI  - Cell biology: the story of i.

PMID- 16598227
TI  - Biologist aims to ease the pain for entrepreneurs.

PMID- 16598230
TI  - Tools needed to navigate landscape of the genome.

PMID- 16598231
TI  - India's concern about both security and sea research.

PMID- 16598232
TI  - Physician-scientists are needed now more than ever.

PMID- 16598233
TI  - Avoiding hazards of best-guess climate scenarios.

PMID- 16598234
TI  - Feline friend or potential foe?

PMID- 16598240
TI  - Palaeontology: a firm step from water to land.

PMID- 16598241
TI  - Evolution: it pays to laze.

PMID- 16598242
TI  - Semiconductors: spray-on silicon.

PMID- 16598243
TI  - Immunology: the pick of the nibbled bits.

PMID- 16598244
TI  - Solar system: when the dust unsettles.

PMID- 16598245
TI  - Archaeology: failure and how to avoid it.

PMID- 16598246
TI  - Fluid dynamics: the rough with the smooth.

PMID- 16598247
TI  - Palaeontology: early Neolithic tradition of dentistry.
AB  - Prehistoric evidence for the drilling of human teeth in vivo has so far been
      limited to isolated cases from less than six millennia ago. Here we describe
      eleven drilled molar crowns from nine adults discovered in a Neolithic graveyard
      in Pakistan that dates from 7,500-9,000 years ago. These findings provide
      evidence for a long tradition of a type of proto-dentistry in an early farming
      culture.

PMID- 16598248
TI  - Parasitology: parasite survives predation on its host.
AB  - As prisoners in their living habitat, parasites should be vulnerable to
      destruction by the predators of their hosts. But we show here that the parasitic
      gordian worm Paragordius tricuspidatus is able to escape not only from its insect
      host after ingestion by a fish or frog but also from the digestive tract of the
      predator. This remarkable tactic enables the worm to continue its life cycle.

PMID- 16598249
TI  - A Devonian tetrapod-like fish and the evolution of the tetrapod body plan.
AB  - The relationship of limbed vertebrates (tetrapods) to lobe-finned fish
      (sarcopterygians) is well established, but the origin of major tetrapod features
      has remained obscure for lack of fossils that document the sequence of
      evolutionary changes. Here we report the discovery of a well-preserved species of
      fossil sarcopterygian fish from the Late Devonian of Arctic Canada that
      represents an intermediate between fish with fins and tetrapods with limbs, and
      provides unique insights into how and in what order important tetrapod characters
      arose. Although the body scales, fin rays, lower jaw and palate are comparable to
      those in more primitive sarcopterygians, the new species also has a shortened
      skull roof, a modified ear region, a mobile neck, a functional wrist joint, and
      other features that presage tetrapod conditions. The morphological features and
      geological setting of this new animal are suggestive of life in shallow-water,
      marginal and subaerial habitats.

PMID- 16598250
TI  - The pectoral fin of Tiktaalik roseae and the origin of the tetrapod limb.
AB  - Wrists, ankles and digits distinguish tetrapod limbs from fins, but direct
      evidence on the origin of these features has been unavailable. Here we describe
      the pectoral appendage of a member of the sister group of tetrapods, Tiktaalik
      roseae, which is morphologically and functionally transitional between a fin and
      a limb. The expanded array of distal endochondral bones and synovial joints in
      the fin of Tiktaalik is similar to the distal limb pattern of basal tetrapods.
      The fin of Tiktaalik was capable of a range of postures, including a limb-like
      substrate-supported stance in which the shoulder and elbow were flexed and the
      distal skeleton extended. The origin of limbs probably involved the elaboration
      and proliferation of features already present in the fins of fish such as
      Tiktaalik.

PMID- 16598251
TI  - A debris disk around an isolated young neutron star.
AB  - Pulsars are rotating, magnetized neutron stars that are born in supernova
      explosions following the collapse of the cores of massive stars. If some of the
      explosion ejecta fails to escape, it may fall back onto the neutron star or it
      may possess sufficient angular momentum to form a disk. Such 'fallback' is both a
      general prediction of current supernova models and, if the material pushes the
      neutron star over its stability limit, a possible mode of black hole formation.
      Fallback disks could dramatically affect the early evolution of pulsars, yet
      there are few observational constraints on whether significant fallback occurs or
      even the actual existence of such disks. Here we report the discovery of mid
      infrared emission from a cool disk around an isolated young X-ray pulsar. The
      disk does not power the pulsar's X-ray emission but is passively illuminated by
      these X-rays. The estimated mass of the disk is of the order of 10 Earth masses,
      and its lifetime (> or = 10(6) years) significantly exceeds the spin-down age of
      the pulsar, supporting a supernova fallback origin. The disk resembles
      protoplanetary disks seen around ordinary young stars, suggesting the possibility
      of planet formation around young neutron stars.

PMID- 16598252
TI  - Isotopic enhancements of 17O and 18O from solar wind particles in the lunar
      regolith.
AB  - Differences in isotopic abundances between meteorites and rocks on Earth leave
      unclear the true composition of the gas out of which the Solar System formed. The
      Sun should have preserved in its outer layers the original composition, and
      recent work has indicated that the solar wind is enriched in 16O, relative to
      Earth, Mars and bulk meteorites. This suggests that self-shielding of CO due to
      photo-dissociation, which is a well understood process in molecular clouds, also
      led to evolution in the isotopic abundances in the early Solar System. Here we
      report measurements of oxygen isotopic abundances in lunar grains that were
      recently exposed to the solar wind. We find that 16O is underabundant, opposite
      to an earlier finding based on studies of ancient metal grains. Our result,
      however, is more difficult to understand within the context of current models,
      because there is no clear way to make 16O more abundant in Solar System rocks
      than in the Sun.

PMID- 16598253
TI  - Quantum interference between two single photons emitted by independently trapped
      atoms.
AB  - When two indistinguishable single photons are fed into the two input ports of a
      beam splitter, the photons will coalesce and leave together from the same output
      port. This is a quantum interference effect, which occurs because two possible
      paths-in which the photons leave by different output ports-interfere
      destructively. This effect was first observed in parametric downconversion (in
      which a nonlinear crystal splits a single photon into two photons of lower
      energy), then from two separate downconversion crystals, as well as with single
      photons produced one after the other by the same quantum emitter. With the recent
      developments in quantum information research, much attention has been devoted to
      this interference effect as a resource for quantum data processing using linear
      optics techniques. To ensure the scalability of schemes based on these ideas, it
      is crucial that indistinguishable photons are emitted by a collection of
      synchronized, but otherwise independent sources. Here we demonstrate the quantum
      interference of two single photons emitted by two independently trapped single
      atoms, bridging the gap towards the simultaneous emission of many
      indistinguishable single photons by different emitters. Our data analysis shows
      that the observed coalescence is mainly limited by wavefront matching of the
      light emitted by the two atoms, and to a lesser extent by the motion of each atom
      in its own trap.

PMID- 16598254
TI  - Solution-processed silicon films and transistors.
AB  - The use of solution processes-as opposed to conventional vacuum processes and
      vapour-phase deposition-for the fabrication of electronic devices has received
      considerable attention for a wide range of applications, with a view to reducing
      processing costs. In particular, the ability to print semiconductor devices using
      liquid-phase materials could prove essential for some envisaged applications,
      such as large-area flexible displays. Recent research in this area has largely
      been focused on organic semiconductors, some of which have mobilities comparable
      to that of amorphous silicon (a-Si); but issues of reliability remain. Solution
      processing of metal chalcogenide semiconductors to fabricate stable and high
      performance transistors has also been reported. This class of materials is being
      explored as a possible substitute for silicon, given the complex and expensive
      manufacturing processes required to fabricate devices from the latter. However,
      if high-quality silicon films could be prepared by a solution process, this
      situation might change drastically. Here we demonstrate the solution processing
      of silicon thin-film transistors (TFTs) using a silane-based liquid precursor.
      Using this precursor, we have prepared polycrystalline silicon (poly-Si) films by
      both spin-coating and ink-jet printing, from which we fabricate TFTs with
      mobilities of 108 cm2 V(-1) s(-1) and 6.5 cm2 V(-1) s(-1), respectively. Although
      the processing conditions have yet to be optimized, these mobilities are already
      greater than those that have been achieved in solution-processed organic TFTs,
      and they exceed those of a-Si TFTs (< or = 1 cm2 V(-1) s(-1)).

PMID- 16598255
TI  - Increased Arctic cloud longwave emissivity associated with pollution from mid
      latitudes.
AB  - There is consensus among climate models that Arctic climate is particularly
      sensitive to anthropogenic greenhouse gases and that, over the next century,
      Arctic surface temperatures are projected to rise at a rate about twice the
      global mean. The response of Arctic surface temperatures to greenhouse gas
      thermal emission is modified by Northern Hemisphere synoptic meteorology and
      local radiative processes. Aerosols may play a contributing factor through
      changes to cloud radiative properties. Here we evaluate a previously suggested
      contribution of anthropogenic aerosols to cloud emission and surface temperatures
      in the Arctic. Using four years of ground-based aerosol and radiation
      measurements obtained near Barrow, Alaska, we show that, where thin water clouds
      and pollution are coincident, there is an increase in cloud longwave emissivity
      resulting from elevated haze levels. This results in an estimated surface warming
      under cloudy skies of between 3.3 and 5.2 W m(-2) or 1 and 1.6 degrees C. Arctic
      climate is closely tied to cloud longwave emission, but feedback mechanisms in
      the system are complex and the actual climate response to the described
      sensitivity remains to be evaluated.

PMID- 16598256
TI  - Deciphering the evolution and metabolism of an anammox bacterium from a community
      genome.
AB  - Anaerobic ammonium oxidation (anammox) has become a main focus in oceanography
      and wastewater treatment. It is also the nitrogen cycle's major remaining
      biochemical enigma. Among its features, the occurrence of hydrazine as a free
      intermediate of catabolism, the biosynthesis of ladderane lipids and the role of
      cytoplasm differentiation are unique in biology. Here we use environmental
      genomics--the reconstruction of genomic data directly from the environment--to
      assemble the genome of the uncultured anammox bacterium Kuenenia stuttgartiensis
      from a complex bioreactor community. The genome data illuminate the evolutionary
      history of the Planctomycetes and allow us to expose the genetic blueprint of the
      organism's special properties. Most significantly, we identified candidate genes
      responsible for ladderane biosynthesis and biological hydrazine metabolism, and
      discovered unexpected metabolic versatility.

PMID- 16598257
TI  - Energetics reveals physiologically distinct castes in a eusocial mammal.
AB  - Eusociality, which occurs among mammals only in two species of African mole-rat,
      is characterized by division of labour between morphologically distinct 'castes'.
      In Damaraland mole-rats (Cryptomys damarensis), colony labour is divided between
      'infrequent worker' and 'frequent worker' castes. Frequent workers are active
      year-round and together perform more than 95% of the total work of the colony,
      whereas infrequent workers typically perform less than 5% of the total work.
      Anecdotal evidence suggests that infrequent workers may act as dispersers, with
      dispersal being limited to comparatively rare periods when the soil is softened
      by moisture. Here we show that infrequent workers and queens increase their daily
      energy expenditure after rainfall whereas frequent workers do not. Infrequent
      workers are also fatter than frequent workers. We suggest that infrequent workers
      constitute a physiologically distinct dispersing caste, the members of which,
      instead of contributing to the work of the colony and helping the queen to
      reproduce, build up their own body reserves in preparation for dispersal and
      reproduction when environmental conditions are suitable.

PMID- 16598258
TI  - An unconventional myosin in Drosophila reverses the default handedness in
      visceral organs.
AB  - The internal organs of animals often have left-right asymmetry. Although the
      formation of the anterior-posterior and dorsal-ventral axes in Drosophila is well
      understood, left-right asymmetry has not been extensively studied. Here we find
      that the handedness of the embryonic gut and the adult gut and testes is reversed
      (not randomized) in viable and fertile homozygous Myo31DF mutants. Myo31DF
      encodes an unconventional myosin, Drosophila MyoIA (also referred to as MyoID in
      mammals; refs 3, 4), and is the first actin-based motor protein to be implicated
      in left-right patterning. We find that Myo31DF is required in the hindgut
      epithelium for normal embryonic handedness. Disruption of actin filaments in the
      hindgut epithelium randomizes the handedness of the embryonic gut, suggesting
      that Myo31DF function requires the actin cytoskeleton. Consistent with this, we
      find that Myo31DF colocalizes with the cytoskeleton. Overexpression of Myo61F,
      another myosin I (ref. 4), reverses the handedness of the embryonic gut, and its
      knockdown also causes a left-right patterning defect. These two unconventional
      myosin I proteins may have antagonistic functions in left-right patterning. We
      suggest that the actin cytoskeleton and myosin I proteins may be crucial for
      generating left-right asymmetry in invertebrates.

PMID- 16598259
TI  - Type ID unconventional myosin controls left-right asymmetry in Drosophila.
AB  - Breaking left-right symmetry in Bilateria embryos is a major event in body plan
      organization that leads to polarized adult morphology, directional organ looping,
      and heart and brain function. However, the molecular nature of the determinant(s)
      responsible for the invariant orientation of the left-right axis (situs choice)
      remains largely unknown. Mutations producing a complete reversal of left-right
      asymmetry (situs inversus) are instrumental for identifying mechanisms
      controlling handedness, yet only one such mutation has been found in mice
      (inversin) and snails. Here we identify the conserved type ID unconventional
      myosin 31DF gene (Myo31DF) as a unique situs inversus locus in Drosophila.
      Myo31DF mutations reverse the dextral looping of genitalia, a prominent left
      right marker in adult flies. Genetic mosaic analysis pinpoints the A8 segment of
      the genital disc as a left-right organizer and reveals an anterior-posterior
      compartmentalization of Myo31DF function that directs dextral development and
      represses a sinistral default state. As expected of a determinant, Myo31DF has a
      trigger-like function and is expressed symmetrically in the organizer, and its
      symmetrical overexpression does not impair left-right asymmetry. Thus Myo31DF is
      a dextral gene with actin-based motor activity controlling situs choice. Like
      mouse inversin, Myo31DF interacts and colocalizes with beta-catenin, suggesting
      that situs inversus genes can direct left-right development through the adherens
      junction.

PMID- 16598260
TI  - Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on
      syntaxin 3.
AB  - Growth of neurite processes from the cell body is the critical step in neuronal
      development and involves a large increase in cell membrane surface area.
      Arachidonic-acid-releasing phospholipases are highly enriched in nerve growth
      cones and have previously been implicated in neurite outgrowth. Cell membrane
      expansion is achieved through the fusion of transport organelles with the plasma
      membrane; however, the identity of the molecular target of arachidonic acid has
      remained elusive. Here we show that syntaxin 3 (STX3), a plasma membrane protein,
      has an important role in the growth of neurites, and also serves as a direct
      target for omega-6 arachidonic acid. By using syntaxin 3 in a screening assay, we
      determined that the dietary omega-3 linolenic and docosahexaenoic acids can
      efficiently substitute for arachidonic acid in activating syntaxin 3. Our
      findings provide a molecular basis for the previously established action of omega
      3 and omega-6 polyunsaturated fatty acids in membrane expansion at the growth
      cones, and represent the first identification of a single effector molecule for
      these essential nutrients.

PMID- 16598261
TI  - Semi-conservative DNA replication through telomeres requires Taz1.
AB  - Telomere replication is achieved through the combined action of the conventional
      DNA replication machinery and the reverse transcriptase, telomerase. Telomere
      binding proteins have crucial roles in controlling telomerase activity; however,
      little is known about their role in controlling semi-conservative replication,
      which synthesizes the bulk of telomeric DNA. Telomere repeats in the fission
      yeast Schizosaccharomyces pombe are bound by Taz1, a regulator of diverse
      telomere functions. It is generally assumed that telomere-binding proteins impede
      replication fork progression. Here we show that, on the contrary, Taz1 is crucial
      for efficient replication fork progression through the telomere. Using two
      dimensional gel electrophoresis, we find that loss of Taz1 leads to stalled
      replication forks at telomeres and internally placed telomere sequences,
      regardless of whether the telomeric G-rich strand is replicated by leading- or
      lagging-strand synthesis. In contrast, the Taz1-interacting protein Rap1 is
      dispensable for efficient telomeric fork progression. Upon loss of telomerase,
      taz1Delta telomeres are lost precipitously, suggesting that maintenance of
      taz1Delta telomere repeats cannot be sustained through semi-conservative
      replication. As the human telomere proteins TRF1 and TRF2 are Taz1 orthologues,
      we predict that one or both of the human TRFs may orchestrate fork passage
      through human telomeres. Stalled forks at dysfunctional human telomeres are
      likely to accelerate the genomic instability that drives tumorigenesis.

PMID- 16598262
TI  - Proton-coupled electron transfer drives the proton pump of cytochrome c oxidase.
AB  - Electron transfer in cell respiration is coupled to proton translocation across
      mitochondrial and bacterial membranes, which is a primary event of biological
      energy transduction. The resulting electrochemical proton gradient is used to
      power energy-requiring reactions, such as ATP synthesis. Cytochrome c oxidase is
      a key component of the respiratory chain, which harnesses dioxygen as a sink for
      electrons and links O2 reduction to proton pumping. Electrons from cytochrome c
      are transferred sequentially to the O2 reduction site of cytochrome c oxidase via
      two other metal centres, Cu(A) and haem a, and this is coupled to vectorial
      proton transfer across the membrane by a hitherto unknown mechanism. On the basis
      of the kinetics of proton uptake and release on the two aqueous sides of the
      membrane, it was recently suggested that proton pumping by cytochrome c oxidase
      is not mechanistically coupled to internal electron transfer. Here we have
      monitored translocation of electrical charge equivalents as well as electron
      transfer within cytochrome c oxidase in real time. The results show that electron
      transfer from haem a to the O2 reduction site initiates the proton pump mechanism
      by being kinetically linked to an internal vectorial proton transfer. This
      reaction drives the proton pump and occurs before relaxation steps in which
      protons are taken up from the aqueous space on one side of the membrane and
      released on the other.

PMID- 16598265
TI  - Denying science.

PMID- 16598263
TI  - Crystal structure of the CorA Mg2+ transporter.
AB  - The magnesium ion, Mg2+, is essential for myriad biochemical processes and
      remains the only major biological ion whose transport mechanisms remain unknown.
      The CorA family of magnesium transporters is the primary Mg2+ uptake system of
      most prokaryotes and a functional homologue of the eukaryotic mitochondrial
      magnesium transporter. Here we determine crystal structures of the full-length
      Thermotoga maritima CorA in an apparent closed state and its isolated cytoplasmic
      domain at 3.9 A and 1.85 A resolution, respectively. The transporter is a funnel
      shaped homopentamer with two transmembrane helices per monomer. The channel is
      formed by an inner group of five helices and putatively gated by bulky
      hydrophobic residues. The large cytoplasmic domain forms a funnel whose wide
      mouth points into the cell and whose walls are formed by five long helices that
      are extensions of the transmembrane helices. The cytoplasmic neck of the pore is
      surrounded, on the outside of the funnel, by a ring of highly conserved
      positively charged residues. Two negatively charged helices in the cytoplasmic
      domain extend back towards the membrane on the outside of the funnel and abut the
      ring of positive charge. An apparent Mg2+ ion was bound between monomers at a
      conserved site in the cytoplasmic domain, suggesting a mechanism to link gating
      of the pore to the intracellular concentration of Mg2+.

PMID- 16598266
TI  - Failed prevention trials leave behind bounty of samples.

PMID- 16598268
TI  - With scores still infected, India declares leprosy 'eliminated'.

PMID- 16598269
TI  - US drug approval ignores science's subtleties, experts say.

PMID- 16598270
TI  - Swedish students protest proposal to cut PhD terms.

PMID- 16598272
TI  - Addictive drugs still best option for attention deficit disorder.

PMID- 16598274
TI  - Drugs down the drain.

PMID- 16598275
TI  - Profile: Thomas Frieden.

PMID- 16598276
TI  - Reply to 'Hormone in the hot seat'.

PMID- 16598277
TI  - Reply to 'Side benefits sway developing nations to choose unneeded vaccines'.

PMID- 16598279
TI  - Stem cell aging: what bleach can teach.

PMID- 16598280
TI  - Streptococcus moves inward.

PMID- 16598282
TI  - Fighting infections with vitamin D.

PMID- 16598281
TI  - Inserting optimism into gene therapy.

PMID- 16598284
TI  - Remodeling in the kidney.

PMID- 16598283
TI  - Remodeling after stroke.

PMID- 16598288
TI  - Ambulatory blood pressure variability and brachial-ankle pulse wave velocity in
      untreated hypertensive patients.
AB  - Blood pressure (BP) variability is estimated as the standard deviation of 24-h
      ambulatory BP. The present study was performed to determine the effect of the
      mean 24-h ambulatory BP values and standard deviations on arterial wall stiffness
      assessed by brachial-ankle pulse wave velocity (baPWV). Brachial-ankle pulse wave
      velocity, carotid intima-media thickness (IMT), urinary albumin excretion (UAE)
      and 24-h ambulatory BP were measured before the start of antihypertensive therapy
      in 203 newly diagnosed hypertensive patients (53.3+/-0.7 years old; clinic
      systolic/diastolic BP: 154+/-1/98+/-1 mm Hg), and univariate and multivariate
      regression analyses of these clinical and biological parameters were performed.
      Univariate regression analyses revealed a significant association between mean
      baPWV values and the standard deviations of ambulatory systolic/diastolic BP.
      Mean ambulatory systolic/diastolic BP values were also associated with UAE, and
      the standard deviations of ambulatory systolic BP were associated with maximum
      carotid IMT. Quintile analyses showed that patients with a mean 24-h ambulatory
      mean BP value and standard deviation below 110 and 20 mm Hg, respectively, had
      the lowest baPWV. Moreover, the multivariate regression analyses confirmed a
      significant correlation between baPWV and the standard deviation of 24-h
      ambulatory systolic BP. In conclusion, untreated hypertensive patients with a
      higher 24-h ambulatory systolic BP variability had stiffer arterial walls.
      Ambulatory systolic BP variability may be involved in stiffening of the arteries
      of hypertensive patients.

PMID- 16598285
TI  - Protein twists and turns in Alzheimer disease.

PMID- 16598289
TI  - 'Office-hour' ambulatory blood pressure monitoring is sufficient for blood
      pressure diagnosis.
AB  - We conducted this study to determine whether 'office hour', defined as time
      period from 0800 to 1800 hours, ambulatory blood pressure monitoring (ABPM)
      predicts daytime ('waking-hour') and 24-h ABPM results, and to examine the impact
      of sleep disturbance on ABPM and nocturnal dip. Eighty-four patients (mean age
      49+/-18 years, 47 males) were studied. Systolic, diastolic and mean 4-, 6-, 8-,
      'office-hour' as well as 'waking-hour' blood pressures (BPs) were obtained from
      24-h ABPM readings. Of these, no statistical differences were found between 8-h
      and 'office-hour' systolic, diastolic and mean BPs compared to 'waking-hour'
      values. There was complete concordance between 'office-hour' and 'waking-hour'
      ABPM diagnosis based on British Hypertension Society definitions. Sleep
      disturbance was found in 22 patients (26%). Although nocturnal dip was not
      significantly different in either sleep-disturbed or non-disturbed patients,
      patients who reported sleep disturbance had significantly higher proportion of
      borderline/abnormal BP diagnosis compared to non-sleep-disturbed counterpart
      during both 'waking hour' and night time. In patients without sleep disturbance,
      there was complete concordance between 'office-hour', 'waking-hour' and 24-h ABPM
      diagnosis based on British Hypertension Society definitions. 'Office-hour' ABPM
      is predictive of 'waking-hour' and 24-h ambulatory BP readings. Sleep disturbance
      is common in patients undergoing the test, and significantly raises the BP
      readings. We therefore propose 'office-hour' ABPM as an accurate, reliable and
      comfortable method of continual non-invasive BP monitoring, and omitting routine
      night time BP monitoring.

PMID- 16598290
TI  - Absence of association between depression and hypertension: results of a
      prospectively designed population-based study.
AB  - The objective of this study was to examine the relation between hypertension and
      depression. In a cross-sectional study of the urban region of a State capital
      with more than 1.5 million inhabitants, 1174 men and women aged 18-80 years,
      selected at random from the population, were studied. Blood pressure,
      hypertension (blood pressure readings >or=140/90 mm Hg or use of blood pressure
      lowering agents), risk factors for hypertension and depression according to the
      Diagnostic and Statistical Manual of Mental Disorders (fourth edition) were
      investigated in home interviews. The prevalence of major depression and
      hypertension were 12.4% (95% confidence interval (CI): 10.5-14.3) and 34.7% (95%
      CI: 32.2-37.4), respectively. Systolic and diastolic blood pressures of
      individuals with and without a lifetime episode of depression were not different
      after adjustment for age and gender. Lifetime episodic major depression was not
      associated with hypertension in bivariate analysis (risk ratios (RR): 0.96, 95%
      CI: 0.76-1.23) and after adjustment for confounding (RR: 1.15; 95% CI:0.75-1.76).
      Hypertension and depression were not associated in this free-living population of
      adults, suggesting that their concomitant occurrence in clinical practice may be
      ascribed to chance.

PMID- 16598291
TI  - Blood pressure measurement in patients with rate controlled atrial fibrillation
      using mercury sphygmomanometer and Omron HEM-750CP deice in the clinic setting.

PMID- 16598292
TI  - Collagen type-I degradation is related to arterial stiffness in hypertensive and
      normotensive subjects.
AB  - Although arterial stiffness is an independent cardiovascular risk factor
      associated with both aging and hypertension, relatively little is known regarding
      the structural changes in the vessel wall that occur with vessel stiffening. We
      determined if collagen type-I metabolism is related to arterial stiffening in
      both hypertensive and normotensive subjects. Arterial stiffness was assessed by
      aortic pulse wave velocity (PWV) and augmentation index (AIx) in 46 subjects
      (48.7 +/- 2 years, 32 hypertensives) and related to circulating markers of
      collagen type-I turnover. Collagen synthesis was assessed by the measurement of
      carboxy-terminal peptide of procollagen type-I (PIP) and collagen degradation by
      the measurement of carboxy-terminal telopeptide of collagen type-I (ICTP), by
      quantitative immunoassay. Matrix metalloproteinase-1 (MMP-1) and the tissue
      inhibitor of metalloproteinase-1 (TIMP-1) were also quantified by immunoassay.
      The ratio of collagen type-I synthesis to degradation was negatively correlated
      with both PWV (P<0.05) and AIx (P<0.05), whereas plasma MMP-1 levels displayed a
      positive correlation with both PWV (P<0.01) and AIx (P<0.01), after adjustment
      for age and mean arterial pressure. The relationship between collagen type-I
      turnover and arterial stiffness was similar in both the normotensive and
      hypertensive subjects. Although circulating markers of collagen synthesis were
      increased in the hypertensive subjects, this was not related to arterial
      stiffness. Collagen type-I degradation is increased in relation to collagen type
      I synthesis in subjects with stiffer arteries. Matrix metalloproteinase-1, the
      enzyme responsible for collagen type-I degradation, is positively related to both
      large elastic and muscular artery stiffness in normotensive and hypertensive
      subjects.

PMID- 16598293
TI  - Changes in the threshold of fetal lung maturity testing and neonatal outcome of
      infants delivered electively before 39 weeks gestation: implications and cost
      effectiveness.
AB  - OBJECTIVE: To compare the neonatal outcome of infants delivered before 39 weeks'
      gestation following documentation of fetal lung maturity before and after the
      lamellar body count (LBC) threshold was increased from 30,000 to 50,000 LB/ul. We
      discuss the algorithm employed for testing fetal lung maturity, the cost of
      testing and potential savings. MATERIAL AND METHODS: We studied the outcome of
      infants delivered electively before 39 weeks' gestation after fetal lung maturity
      was documented by amniotic fluid analysis. We compared the outcome of neonates
      born before and after the LBC threshold was increased. RESULTS: Our cohort
      included 527 neonates who were divided into two groups: 264 who underwent fetal
      lung maturity studies before the change in LBC threshold and 263 who underwent
      testing after the change. In the first group, 158 neonates met the criteria of
      LBC >30,000 LB/ul and were delivered without further testing. The second group
      included 154 neonates who were mature by LBC >50,000 LB/ul and were delivered.
      Seven of the neonates born in the first group required admission to the neonatal
      intensive care unit (NICU), whereas in the second group only two neonates
      required admission (P = 0.02). Additionally, 16 neonates in the first group
      required respiratory assistance compared with six in the second group (P = 0.04).
      The overall neonatal complication rate was significantly higher in the first
      group (P = 0.001). CONCLUSION: Changing the LBC threshold resulted in a
      significant decrease in neonatal morbidity. Employing the algorithm, we described
      for testing fetal lung maturity is cost effective, and more importantly,
      represents sound evidence-based medical management.

PMID- 16598294
TI  - Pulse oximetry in very low birth weight infants: can oxygen saturation be
      maintained in the desired range?
AB  - OBJECTIVE: To determine if a change in the pulse oximeter goal range and high
      alarm limit for oxygen saturation (SpO2) alters the distribution of SpO2 for
      premature infants in oxygen. STUDY DESIGN: This was a prospective, observational
      analysis. For group 1 (February 2002 to April 2002, n = 23), pulse oximeter
      alarms were set at 80% (low) and 96% (high), and the goal range was 90-95%. For
      group 2 (May 2002 to August 2003, n = 49), the high alarm was lowered to 94%, and
      the goal range was 88 to 94%. The SpO2 values for 24 h were downloaded from
      Nellcor pulse oximeters during the two periods and the percent time within, above
      and below the goal range was derived and compared. RESULTS: Groups were similar
      except for use of post-natal steroids (group 2 > 1). The percent time within
      (57.7+/-9.8 vs 59.4+/-12.4%), above (15.4+/-10.6 vs 14+/-9.4%) and below (26.9+/
      9.7 vs 26.6+/-10.2%) the goal range was similar for groups 1 and 2, respectively.
      However, the percent time with SpO2 <80% increased significantly for group 2
      (4.0+/-2.7 vs 1.9+/-1.4%). CONCLUSIONS: Changes in pulse oximeter policy and
      alarms in labile, sick premature infants need evaluation for their effects on the
      distribution of SpO2 values before routine use.

PMID- 16598295
TI  - Are newborns receiving premedication before elective intubation?
AB  - AIMS: To determine the extent and type of premedication used for elective
      endotracheal intubation in neonatal intensive care units (NICUs). METHODS: A
      pretested questionnaire was distributed via e-mail to the program directors of
      the neonatology divisions with accredited fellowship programs in Neonatal
      Perinatal Medicine in the United States. RESULTS: Of the 100 individuals
      contacted, 78 (78%) participated in the survey. Only 34 of the 78 respondents
      (43.6%) always use any premedication for elective intubation. Nineteen
      respondents (24.4%) reported to have a written policy regarding premedication.
      Morphine or fentanyl was used most commonly (57.1%), with a combination of
      opioids and midazolam or other benzodiazepines used less frequently. Fourteen
      respondents (25%) also use muscle relaxants with sedation for premedication, but
      only nine respondents combined paralysis with atropine and sedation. CONCLUSION:
      Most neonatology fellowship program directors do not report always using
      premedication for newborns before elective endotracheal intubation despite strong
      evidence of physiologic and practical benefits. Only a minority of the NICUs has
      written guidelines for sedation, which may preclude effective auditing of this
      practice. Educational interventions may be necessary to ensure changes in
      clinical practice.

PMID- 16598296
TI  - A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus
      immune globulin.
AB  - OBJECTIVES: Very low birth weight (VLBW) infants are vulnerable to nosocomial
      infections and subsequent morbidity; including infections caused by
      Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by
      capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal
      investigational human immunoglobulin G (IgG) with high levels of opsonizing S.
      aureus CPS types 5 and 8 IgG. METHODS: A Phase 2 clinical trial to assess the
      safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter
      study were randomized to receive two identical 20 ml/kg i.v. infusions of either
      0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days
      after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8
      IgG levels were measured preinfusion and at various times after each infusion.
      RESULTS: Of 206 neonates, 158 received both infusions. Adverse events were
      similar in the two treatment groups. Six subjects (3% in each group) discontinued
      owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642
      mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses,
      respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to
      1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels
      were similar. Geometric mean IgG levels among placebo recipients were
      consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three
      episodes of S. aureus bacteremia occurred in each arm. CONCLUSIONS: Infusion of
      Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5
      and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune
      globulin was well tolerated in this population.

PMID- 16598298
TI  - Digital divide and digital dividend in the age of information technology.

PMID- 16598297
TI  - Does birth weight discordance in preterm twins affect neonatal outcome?
AB  - OBJECTIVE: To compare neonatal morbidity and mortality between hospitalized
      discordant and concordant preterm twin pairs. STUDY DESIGN: This was a
      retrospective, hospital-based study of preterm twins, followed in neonatal
      intensive care unit. Twins were classified as discordant when the difference in
      birth weight was >15%. Morbidity and mortality rates were compared between
      discordant and concordant groups. RESULTS: Of 136 preterm twins in the study, 54
      were discordant and 82 were concordant. In discordant twins hypoglycemia and
      cesarean delivery rate was higher than concordant pairs. The mortality rate did
      not differ between concordant and discordant groups. CONCLUSIONS: Hospitalized
      preterm discordant twin pairs have an increased risk of hypoglycemia compared to
      concordants. Discordant growth is not a risk factor for prolonged hospitalization
      and increased mortality.

PMID- 16598300
TI  - Ninth commandment: 'Thou shalt not covet thy neighbor's wife!' Penetrating trauma
      to the corpora cavernosa caused by gunshot.
AB  - We describe a case of gunshot wound to the corpora cavernosa caused by a low
      velocity bullet in a 43-year-old man. He volunteered that his lover's husband
      shot him with a handgun. The bullet had penetrated the right gluteal region with
      no exit wound causing a right corpus cavernosum lesion. A penile colour-duplex
      doppler ultrasonography did not reveal injuries of the cavernosal arteries or
      altered peak diastolic and systolic values. A three-dimensional computed
      tomography study corfirmed the presence of the bullet at the root of the right
      corpus cavernosum and allowed to identify the curvilinear ballistic trajectory,
      confirming a low-velocity penetrating bullet. The patient underwent exploratory
      surgery with removal of the bullet and primary repair of the identified
      unilateral albuginea rupture. The bullet, passing through clothing, probably
      slowed down causing less than expected harm. The follow-up visit after 2 months
      showed that the penile girth was not narrowed by such a repair. With a 2-year
      follow-up the patient has a normal penile ultrasound morphology and a normal
      sexual activity.

PMID- 16598299
TI  - Co-transplantation of bone marrow stromal cells transduced with IL-7 gene
      enhances immune reconstitution after allogeneic bone marrow transplantation in
      mice.
AB  - Allogeneic bone marrow transplantation (allo-BMT) is followed by a period of
      profound immune deficiency, which results in significant susceptibility to
      infections and limits the extensive application of this approach in clinic. Here,
      we transduced human interleukin-7 (IL-7) gene into donor-derived bone marrow
      stromal cells (MSCs) using adenovirus vector, and transplanted this gene
      engineered MSCs (MSC-IL-7) into lethally irradiated C57BL/6 mice to investigate
      their effects on immune reconstitution following allo-BMT. Recipient mice
      receiving MSC-IL-7 cells plus T-cell-depleted bone marrow cells of BALB/c mice
      showed a significant increase in thymopoiesis and homeostatic expansion of
      peripheral T lymphocytes. Furthermore, injection of MSC-IL-7 cells following allo
      BMT protected the host from the lethality caused by acute graft-versus-host
      disease (GVHD) and prevented the occurrence of GVHD induced by transplanted T
      cells. Thus, the use of MSC-IL-7 cells may be therapeutically useful for
      enhancing immune reconstitution without aggravating GVHD in allo-BMT mice.

PMID- 16598301
TI  - Inducible expression of AML1-ETO fusion protein endows leukemic cells with
      susceptibility to extrinsic and intrinsic apoptosis.
AB  - AML1-ETO, a leukemia-associated fusion protein generated by the frequently
      occurred chromosome translocation t(8;21) in acute myeloid leukemia, was shown to
      exert dichotomous functions in leukemic cells, that is, growth arrest versus
      differentiation block. By the analysis of oligonucleotide microarray, AML1-ETO
      was shown to modulate the expressions of an impressive array of pro- and anti
      apoptotic genes. Here, we investigate potential effects of the ecdysone inducible
      AML1-ETO expression on apoptosis of leukemic U937 cell line. We show that AML1
      ETO significantly stabilizes death receptor Fas protein and increases
      proapoptotic Bak in addition to reducing Bcl-2 expression. Accordingly, inducible
      AML1-ETO expression is followed by apoptosis to a lower degree. Especially, AML1
      ETO endows leukemic cells with the susceptibility to anti-Fas agonist antibody,
      ultraviolet light and camptothecin analog NSC606985-induced apoptosis with
      increased activation of caspase-3/8. Considering that apoptosis-enhancing effect
      of AML1-ETO would not be favorable to the leukemogenesis harboring the t(8;21)
      translocation, it must be overcome to fulfill their leukemogenic potential.
      Complementary to this prediction is that two AML1-ETO-carrying leukemic cells,
      Kasumi-1 and SKNO-1, present similar sensitivity to apoptosis induction with AML1
      ETO-negative leukemic cells. Therefore, genetic and/or epigenetic screenings of
      apoptosis-related genes modulated by AML1-ETO deserve to be explored for
      understanding the mechanisms of AML1-ETO-induced leukemogenesis.

PMID- 16598302
TI  - Methylation analysis of asparagine synthetase gene in acute lymphoblastic
      leukemia cells.

PMID- 16598303
TI  - Essential thrombocythemias without V617F JAK2 mutation are clonal hematopoietic
      stem cell disorders.

PMID- 16598304
TI  - Identification of truncated RUNX1 and RUNX1-PRDM16 fusion transcripts in a case
      of t(1;21)(p36;q22)-positive therapy-related AML.

PMID- 16598305
TI  - Twenty-seven cases of drug-induced interstitial lung disease associated with
      imatinib mesylate.

PMID- 16598307
TI  - Aberrant gene promoter methylation marking disease progression in multiple
      myeloma.

PMID- 16598306
TI  - JAK2 V617F is a rare finding in de novo acute myeloid leukemia, but STAT3
      activation is common and remains unexplained.
AB  - Signal transducer and activator of transcription (STAT) proteins are
      phosphorylated and activated by Janus kinases (JAKs). Recently, several groups
      identified a recurrent somatic point mutation constitutively activating the
      hematopoietic growth factor receptor-associated JAK2 tyrosine kinase in diverse
      chronic myeloid disorders - most commonly classic myeloproliferative disorders
      (MPD), especially polycythemia vera. We hypothesized that the JAK2 V617F mutation
      might also be present in samples from patients with acute myeloid leukemia (AML),
      especially erythroleukemia (AML-M6) or megakaryoblastic leukemia (AML-M7), where
      it might mimic erythropoietin or thrombopoietin signaling. First, we documented
      STAT3 activation by immunoblotting in AML-M6 and other AML subtypes.
      Immunoperoxidase staining confirmed phosphorylated STAT3 in malignant myeloblasts
      (21% of cases, including all AML-M3 samples tested). We then analyzed genomic DNA
      from 162 AML, 30 B-cell lymphoma, and 10 chronic lymphocytic leukemia (CLL)
      samples for JAK2 mutations, and assayed a subset for SOCS1 and FLT3 mutations.
      Janus kinase2 V617F was present in 13/162 AML samples (8%): 10/13 transformed
      MPD, and three apparent de novo AML (one of 12 AML-M6, one of 24 AML-M7, and one
      AML-M2 - all mixed clonality). FLT3 mutations were present in 5/32 (16%), while
      SOCS1 mutations were totally absent. Lymphoproliferative disorder samples were
      both JAK2 and SOCS1 wild type. Thus, while JAK2 V617F is uncommon in de novo AML
      and probably does not occur in lymphoid malignancy, unexplained STAT3 activation
      is common in AML. Janus kinase2 extrinsic regulators and other proteins in the
      JAK-STAT pathway should be interrogated to explain frequent STAT activation in
      AML.

PMID- 16598308
TI  - Activation of FGFR1beta signaling pathway promotes survival, migration and
      resistance to chemotherapy in acute myeloid leukemia cells.
AB  - Fibroblast growth factors (FGFs) are important regulators of hematopoiesis and
      have been implicated in the tumorigenesis of solid tumors. Recent evidence
      suggests that FGF signaling through FGF receptors (FGFRs) may play a role in the
      proliferation of subsets of acute myeloid leukemias (AMLs). However, the precise
      mechanism and specific FGF receptors that support leukemic cell growth are not
      known. We show that FGF-2, through activation of FGFR1beta signaling, promotes
      survival, proliferation and migration of AML cells. Stimulation of FGFR1beta
      results in phosphoinositide 3-kinase (PI3-K)/Akt activation and inhibits
      chemotherapy-induced apoptosis of leukemic cells. Neutralizing FGFR1-specific
      antibody abrogates the physiologic and chemoprotective effects of FGF-2/FGFR1beta
      signaling and inhibits tumor growth in mice xenotransplanted with human AML.
      These data suggest that activation of FGF-2/FGFR1beta supports progression and
      chemoresistance in subsets of AML. Therefore, FGFR1 targeting may be of
      therapeutic benefit in subsets of AML.

PMID- 16598309
TI  - The fibroblast growth factors in multiple myeloma.

PMID- 16598310
TI  - Autoimmune hemolytic anemias and IgG antierythrocyte autoantibodies in
      Waldenstrom's macroglobulinemia: association with FcgammaRIIa polymorphism.

PMID- 16598311
TI  - Identification of genes involved in imatinib resistance in CML: a gene-expression
      profiling approach.
AB  - The use of the tyrosine kinase inhibitor imatinib, which blocks the enzymatic
      action of the BCR-ABL fusion protein, has represented a critical advance in
      chronic myeloid leukemia (CML) treatment. However, a subset of patients initially
      fails to respond to this treatment. Use of complementary DNA (cDNA) microarray
      expression profiling allows the identification of genes whose expression is
      associated with imatinib resistance. Thirty-two CML bone marrow samples,
      collected before imatinib treatment, were hybridized to a cDNA microarray
      containing 6500 cancer genes, and analyzed using bootstrap statistics. Patients
      refractory to interferon-alpha treatment were evaluated for cytogenetic and
      molecular responses for a minimum of 12 months. A set of 46 genes was
      differentially expressed in imatinib responders and non-responders. This set
      includes genes involved in cell adhesion (TNC and SCAM-1), drug metabolism
      (cyclooxygenase 1), protein tyrosine kinases and phosphatases (BTK and PTPN22). A
      six-gene prediction model was constructed, which was capable of distinguishing
      cytogenetic response with an accuracy of 80%. This study identifies a set of
      genes that may be involved in primary resistance to imatinib, suggesting BCR-ABL
      independent mechanisms.

PMID- 16598312
TI  - Acquisition of JAK2, PTPN11, and RAS mutations during disease progression in
      primary myelodysplastic syndrome.

PMID- 16598314
TI  - Meningoencephalitis, pancytopenia, pulmonary insufficiency and splenic abscess in
      a patient with brucellosis.
AB  - A complicated case of brucellosis with some rare features is reported.
      Brucellosis is a multisystemic disease. However, disseminated brucellosis with
      cerebral, pulmonary, hematopoietic and splenic involvement in an otherwise
      healthy patient is a rare event. In this article, we report a case of
      disseminated brucellosis who was initially diagnosed as myelodysplastic syndrome
      MDS and meningoencephalitis, pulmonary symptoms, and splenic abscess formation
      occurred thereafter.

PMID- 16598315
TI  - A young patient with rash in the lower limbs. Henoch-Schonlein purpura.

PMID- 16598313
TI  - Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core
      binding factor acute myeloid leukemia (CBF-AML).
AB  - In core binding factors (CBF) acute myeloid leukemia (AML), the disruption of
      CBFalpha/beta genes impairs normal hematopoietic differentiation and is supposed
      to cooperate with additional mutations promoting proliferation. The incidence and
      the prognosis of receptor tyrosine kinase (RTK) c-Kit and FLT3 mutations and Ras
      mutations were evaluated in 103 pediatric and adult patients with CBF-AML. c-Kit
      mutations were present in 17% patients. c-Kit exon 8 mutations were more frequent
      in inv(16) than in t(8;21) subset (20 versus 6%). Only one patient had FLT3-ITD
      but FLT3-D835 was as frequent as reported in AML population (7%). Ras mutations
      were significantly more frequent in inv(16) than in t(8;21) subset (36 versus 8%,
      P=0.001). RTK mutations were associated with a higher white blood cell count
      (WBC) (36 versus 21 G/L, P=0.05). FLT3 mutations were significantly associated
      with a shorter EFS and survival (P<0.0001 and P=0.0002) owing to an excess of
      early events. c-Kit mutations were associated with a shorter EFS and RFS (P=0.002
      and P=0.003) in t(8;21) but not inv(16) patients. As previously observed, Ras
      mutations did not affect prognosis. Screening for RTK mutations may help to
      identify patients with a more adverse outcome and thus susceptible to benefit
      from intensified protocols or RTK inhibitors.

PMID- 16598316
TI  - Pregnant women with type 1 diabetes mellitus treated by glargine insulin.

PMID- 16598317
TI  - Pathophysiology and hemodynamic of postresuscitation syndrome.
AB  - The fatal outcome of victims after initially successful resuscitation for cardiac
      arrest has been attributed both to global myocardial ischemia during the cardiac
      arrest and the adverse effects of reperfusion. Postresuscitation syndrome
      comprises 2 major components; pathophysiologic postresuscitation disease and
      postresuscitation hemodynamic changes. Both components predict the myocardial
      function, which in its turn will outline the outcome of the resuscitation effort.
      Awareness of those components before and early after restoration of the
      circulation will improve the outcomes of cardiopulmonary resuscitation.

PMID- 16598318
TI  - Acinar cell ultrastructure after taurine treatment in rat acute necrotizing
      pancreatitis.
AB  - OBJECTIVE: To evaluate the organelle-based changes in acinar cells in
      experimental acute necrotizing pancreatitis (ANP) after taurine treatment and the
      association of electron microscopic findings with histopathological changes and
      oxidative stress markers. METHODS: The study was performed in February 2005 at
      Gulhane School of Medicine and Hecettepe University, Turkey. Forty-five rats were
      divided into 3 groups. Acute necrotizing pancreatitis was induced in groups II
      and III. Groups I and II were treated with saline and Group III with taurine 1000
      mg/kg/day, i.p, for 48 hours. Histopathological and ultrastructural examinations
      were determined using one-way analysis of variance and Kruskal-Wallis tests.
      RESULTS: Histopathologic findings improved significantly after taurine treatment.
      Degree of injury in rough and smooth endoplasmic reticulums, Golgi apparatus,
      mitochondria and nucleus of acinar cells also decreased with taurine in
      correlation with biochemical and histological results. CONCLUSION: Taurine
      improves acinar cell organelle structure, and ultrastructural recovery in ANP
      reflects histological improvement.

PMID- 16598319
TI  - Effects of vitamin E and gemfibrozil on lipid profiles, lipid peroxidation and
      antioxidant status in the elderly and young hyperlipidemic subjects.
AB  - OBJECTIVE: This study has dealt with the effects of gemfibrozil and vitamin E
      (vit E) therapies on lipoprotein levels, lipid peroxidation and antioxidant
      statuses of the elderly and young hyperlipidemic subjects. METHODS: This study
      took place in the Internal Medicine Clinic, Faculty of Medicine, Osmangazi
      University, Turkey between 2004-2005. This study was carried out on 99
      hyperlipidemic and 40 control subjects. Subjects were divided into 2 groups;
      elderly hyperlipidemic (n=65) and young hyperlipidemic (n=34). In the young and
      elderly hyperlipidemic subjects of the first group treated only with vit E (600
      mg/day) for one month. In the young and elderly hyperlipidemic subjects of the
      second group were treated only with gemfibrozil (600 mg/twice daily) for one
      month. The 2 therapies of vit E and gemfibrozil were then combined and applied to
      the third group of our study. Reduced glutathione (GSH), glutathione peroxidase
      (GPx), total cholesterol (total chol), serum low density lipoprotein (LDL), high
      density lipoprotein (HDL), triglyceride (TG), vit E, malondialdehyde (MDA),
      superoxide dismutase (SOD) levels of the 3 groups were measured. RESULTS: In
      elderly hyperlipidemic therapy group: vit E groups, the post-treatment vit E
      levels increased. In the gemfibrozil groups, post-treatment TG level decreased
      whereas HDL level increased. In the vit E plus gemfibrozil groups, post-treatment
      TG level decreased, HDL, and vit E levels increased. In young hyperlipidemic
      therapy group: vit E groups, the post-treatment HDL, vit E, GSH, GPX levels
      increased whereas LDL, MDA, levels decreased. In the gemfibrozil groups, post
      treatment TG, LDL decreased, HDL level increased. In the vit E plus gemfibrozil
      groups, post-treatment TG, LDL, MDA levels decreased whereas HDL, vit E, GSH
      levels increased. CONCLUSION: When combined, gemfibrozil and vit E are effective
      in preventing cardiovascular diseases.

PMID- 16598320
TI  - The relation between tumor marker Ca 15-3 and metastases in interpectoral lymph
      nodes in breast cancer patients.
AB  - OBJECTIVE: We aimed at analyzing the metastatic involvement in interpectoral
      (Rotter's) lymph nodes (RLN) in relation to tumor marker CA 15-3. METHODS: The
      study included 177 female patients undergoing surgery for primary breast cancer
      at the University Hospital for Tumors, Zagreb, Croatia from November 2001 to
      March 2004. In addition to the standard surgical procedure, interpectoral RLNs
      were removed in all of the patients. Levels of the serum tumor marker CA 15-3 was
      determined prior to surgery. RESULTS: Rotter's lymph nodes were identified in
      66.2% of the patients, with metastatic involvement revealed in 18.6% of the RLNs.
      Metastatic involvement of RLNs in patients with negative axillary lymph nodes was
      2.8% and positive in 34.6%. Elevated serum levels of tumor marker CA 15-3 had 22
      (12.4%) patients. Of 33 Rotter's node-positive patients, 27.3% had elevated serum
      levels of tumor marker CA 15-3 and in Rotter's node-negative patients only 9% had
      elevated serum levels of tumor marker CA 15-3, with the level statistically
      significantly higher in Rotter's positive patients compared to those with
      negative (or absent) RLNs (chi2=8.22, p=0.004). CONCLUSION: Tumor marker CA 15-3
      is more frequently elevated in patients with positive RLNs. Elevated values of
      tumor marker CA 15-3 could be warning for possible positive interpectoral nodes.
      The removal of the RLNs may be beneficial for patients with (massive) axillary
      nodal involvement. For axillary node negative patients, sentinel node biopsy
      could avoid the unnecessary removal of the RLNs.

PMID- 16598321
TI  - Gene expression profiles of the fibroblasts from breast tumors and normal tissue
      compared with the tumor expression profiles.
AB  - OBJECTIVE: The study was designed to examine whether the gene expression profiles
      of fibroblast cell lines, established from the tumor and the normal tissue from
      the same breast, exhibit any similarities with the profiles of the original
      tissues. METHODS: Fibroblast cell lines were established from invasive ductal
      carcinoma (IDC) and ductal carcinoma in situ (DCIS) of the breast and the
      adjacent normal tissues. Isolated total RNA from the cell lines and tissues were
      used to prepare labeled cDNA which was hybridized to Becton Dickinson Atlas
      microarrays for obtaining profiles of expressed genes. The profiles of tumors and
      cell lines were compared. This study was carried out at King Faisal specialist
      Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia, during 2004 and
      2005. RESULTS: Alterations of expression of most of the genes in the tissues were
      not detectable in the cell lines. The expression of a lower number of genes was
      altered in DCIS compared with that in IDC tumors. CONCLUSION: Although the
      fibroblasts discharge important functions, their gene expression profiles do not
      represent the breast tissue to the extent that any prognostic decisions could be
      made.

PMID- 16598323
TI  - Serum leptin levels and malnutrition in patients with chronic renal failure.
AB  - OBJECTIVE: To investigate the correlation between serum leptin levels, body mass
      index, and triceps skin fold thickness, which are anthropometric measurements, as
      well as serum albumin levels in patients with chronic renal failure on
      hemodialysis. METHODS: We studied 75 patients (48 males, 27 females; ages between
      18-82) at the Hemodialysis Unit, Cumhuriyet University Medical School; Private
      Sivas Dialysis Center; Hemodialysis Unit, Sultan Izzettin Keykavus Hospital; and
      the Hemodialysis Unit, SSK Sivas Hospital between January 2003 and February 2004.
      Patients were excluded if they had been on dialysis for less than one year, if
      they were anuric, or if they had been on dialysis with jugular or subclavian
      catheter and long-term permanent port catheter. Similarly, patients with diabetes
      mellitus, chronic pulmonary disorders, and hepatic cirrhosis or hepatitis B,
      hepatitis C carriers as well as those on active tuberculosis therapy were
      excluded. C-reactive protein was measured in all patients and those with above
      normal values were excluded. RESULTS: While the mean age for the males was 44.52
      +/- 16.53 years (18-77), it was 48.29 +/- 14.32 years (22-82) for the females.
      The mean triceps skin fold thickness for males was 6 +/- 1.81 mm (3-11.3 mm), and
      for females, it was 14.07 +/- 8.79 mm (4.3-33.3 mm). The mean body mass index for
      males was 20.77 +/- 2.61 kg/m2 (14.8-26.6 kg/m2), and for females, it was 25.36
      +/- 6.47 kg/m2 (17.3-42.2 kg/m2). The mean serum leptin level for males was 4.61
      +/- 4.20 ngr/dl (0.1-18.7 ngr/dl), and for females, it was 52.06 +/- 61.67 ngr/dl
      (0.6-172.5 ngr/dl). A positive correlation was observed between triceps skin fold
      thickness and leptin, both in the male group (r=0.478; p<0.05), and in the female
      group (r=0.876; p<0.05). Body mass index and leptin were also correlated
      positively both in the male group (r=0.502; p<0.05) and in the female group
      (r=0.905; p<0.05). No correlation was established between serum albumin levels
      and leptin. Leptin did not correlate with other measured parameters CONCLUSION:
      Our study demonstrates that serum leptin levels positively correlated with body
      mass index and triceps skin fold thickness, which are malnutrition parameters.
      Therefore, the leptin hormone may be utilized in obtaining preliminary
      information regarding malnutrition.

PMID- 16598322
TI  - Comparing the clinical, histopathological and myoepithelial features of estrogen
      receptor positive and negative mammary carcinomas.
AB  - OBJECTIVE: The purpose of this study is to examine the relationship between
      hormone-receptor status and histological parameters, considering that some
      estrogen receptor (ER)-negative breast carcinoma are suggested to be of
      myoepithelial origin or differentiation; and to examine the presence of
      significant difference by myoepithelial markers and define their morphologies.
      METHODS: For this research, 30 estrogen receptor-negative and 31 estrogen
      receptor-positive breast carcinomas diagnosed at the Pathology Department,
      Istanbul Training and Education Hospital, Istanbul, Turkey, between February 2003
      and October 2004 were considered and compared clinically, microscopically and
      immunohistochemically considering myoepithelial markers using SMA, S100,
      keratin14. RESULTS: We found a higher amount of grade 3 frequency pushing
      margins, solid islets, and presence of central necrosis in the estrogen receptor
      negative group than in the positive group (p<0.001 and p<0.05). Six estrogen
      negative and 2 estrogen-positive cases were found positive for myoepithelial
      markers; a difference which is non-significant (p=0.147). The presence of solid
      islets, fusiform, and clear cells was detected higher in myoepithelial positive
      tumors than in negative group (p<0.05). CONCLUSION: For daily pathologic
      applications, some morphological properties of a breast carcinoma can give clues
      about ER and myoepithelial features. In estrogen receptor-negative tumors, there
      is a remarkable myoepithelial marker positivity. Studies involving broader series
      and different myoepithelial markers could give more reliable results.

PMID- 16598324
TI  - Blood pressure profiles and hypertension in Iraqi primary school children.
AB  - OBJECTIVE: To elucidate blood pressure (BP) levels and the prevalence of
      hypertension (HT); as well as to address some epidemiological variables which
      contributes to BP and suggest certain primordial guidelines for control and
      prevention of childhood HT. METHODS: A cross-sectional study recruiting 1427
      (46.1% boys versus 53.9% girls) school aged students (6-12 years) from 8 primary
      schools in Baghdad during the period November 2001 to May 2002. The BP readings
      were plotted adopting principles of the 1996 American Task Force on High Blood
      Pressure in Children and Adolescents. RESULTS: For both genders, the combined
      mean systolic blood pressure (SBP) was 106.66 +/- 9.03 mm Hg and combined mean
      diastolic blood pressure (DBP) was 67.09 +/- 7.98 mm Hg. There was no significant
      statistical differences noted with respect to SBP and DBP among boys and girls
      except at the age range of 10-12 years, where girls manifest higher SBP (p<0.01)
      and DBP (p<0.05) than boys. Obesity was reported in 7.3% of sample with
      significant girl's preponderance (3.2% for boys versus 4.1% for girls, p<0.05).
      Hypertension was recorded 1.8 fold higher among obese (4.7%) than non-obese
      children (2.6%) (p<0.05). Multiple regression analysis showed positive and
      significant correlation of age, weight, height and body mass index with each SBP
      and DBP. The overall prevalence of HT was 1.7% with significantly higher systolic
      HT (1.1%) than diastolic HT (0.6%) (p<0.05) but with no significant gender
      distribution (0.8% for boys versus 0.9% for girls). For both genders in the
      hypertensive group, the mean SBP was 127.66 +/- 5.46 mm Hg and DBP was 77.26 +/-
      6.19 mm Hg. CONCLUSION: Despite the low prevalence of our childhood HT (1.7%)
      compared to some Arabian and foreign countries, careful approach to the problem
      deems crucial through routine recording of BP and constructing our own national
      nomograms, age, gender and height specific, inspired from our nutritional,
      cultural, ethnic and social backgrounds. Moreover, implementing school heart
      health curriculum seems tentative to interrupt or ameliorate progression of HT as
      our children enter adulthood.

PMID- 16598325
TI  - Human papillomavirus infection among women attending health facilities in the
      Kingdom of Bahrain.
AB  - OBJECTIVE: To investigate the occurrence of human papillomavirus (HPV) infection
      and the associated risk factors in Bahrain's female population. METHODS: This
      study was carried out between March to December 2004, which includes cervical
      scrapings for Pap smear and HPV-DNA testing using polymerase chain reaction (PCR)
      and restriction fragment length polymorphism (RFLP) analysis, obtained from 100
      women attending the Gynecology Clinic at Salmaniya Medical Center and Sheikh
      Sabah Health Center in the Kingdom of Bahrain. We distributed questionnaires that
      include the sociodemographic data as well as information on risk factors such as
      smoking, parity, and the contraceptive used. RESULTS: Eleven women (11%) with
      normal cytology were HPV-positive. The RFLP analysis detected HPV-types 16, 18,
      45, 62 and 53. Positive women were significantly older (43.3 +/- 10.1 years) than
      negatives (36.5 +/- 9.9 years; p=0.04), however, there was no difference in age
      of first sexual contact (positive: 18.1 +/- 5.7 years versus negative: 20.6 +/-
      4.4 years). Polygamy, smoking and hormonal contraception was not identified as
      risk factors, but positive women showed higher parity. CONCLUSION: In this study
      on HPV infection in Bahrain, the 11% positivity with high risk HPV types, in the
      presence of normal cytology suggests that in addition to the cervical cancer
      screening program, offer of HPV testing deserves consideration.

PMID- 16598326
TI  - Initial experience with an intensive care hyperglycemia protocol in a Saudi
      Arabian intensive care unit.
AB  - OBJECTIVE: To study the efficacy of nurse-driven intensive glucose management
      protocol in an intensive care setting. METHODS: This cohort study took place at
      King Abdul-Aziz National Guard Hospital, Al-Hasa, Saudi Arabia from April 2005
      through June 2005. We modified a validated nurse-driven glycemic protocol when
      glucose level was >11.1 mmol/L. Protocol was applied to 103 consecutive patients.
      Three months after implementing the protocol, we analyzed the glucose control and
      relevant patient variables. To check the efficacy, glucose values were compared
      with patients admitted consecutively 2 months prior to the implementation of the
      protocol. Duration and mean insulin infusion rates were also recorded. A brief
      nursing survey was also conducted. RESULTS: The median blood glucose upon ICU
      admission was 8.7 mmol/L (interquartile range 6.9-12.05). Our cohort included 45
      patients with history of diabetes while the remaining 58 were non-diabetics. Mean
      blood glucose decreased from 10 +/- 4.4 mmol/L on admission to 8.2 +/- 1.8 mmol/L
      for the duration of ICU stay. Protocol was effective in both diabetics and non
      diabetics. Insulin infusion was employed in 33 patients. Median insulin infusion
      rate required throughout the ICU length of stay was 4.3 units/hour. Duration and
      rate of insulin infusion were not statistically significant between diabetics and
      non-diabetics. The glucose control was significantly better when compared with
      the prior practices of glucose control. CONCLUSION: Our study demonstrates that
      nurse-driven hyperglycemia protocol were manageable to used in critically ill
      patients. Moreover, the protocol is equally effective in both diabetic and non
      diabetic patients.

PMID- 16598327
TI  - Characteristics of poisoning cases in adult intensive care unit in Sanliurfa,
      Turkey.
AB  - OBJECTIVE: The aim of this prospective study was to analyze the rate and
      characteristics of acute poisoning cases admitted to adult intensive care unit
      (ICU). METHODS: All cases of acute poisoning admitted to ICU of the Harran
      University Hospital, Turkey, between July 2002 and May 2005, were included in
      this study. Clinical, laboratory, and demographic characteristics, type of poison
      and patient's outcomes were recorded. RESULTS: There were 86 poisoning cases
      among 844 patients admitted to the ICU. The mean age was 26 +/- 9 years and the
      majority of the patients (56.9%) were 15-24 years of ages. Eighty percent of
      acute poisonings were self-inflicted and 65.2% of these patients were singles.
      Medical drugs overdose were the major cause (51.2%) of intoxication followed by
      agricultural chemicals (37.2%). The most frequently involved medicinal drugs were
      benzodiazepines, antidepressants and analgesics. Eleven patients in pesticides
      rodenticides and 9 patients in other medical drugs poisoning have required
      mechanical ventilation between 1-12 days. The duration of the intensive care stay
      was 6.4 +/- 4.3 days. Five cases (5.8%) with acute poisonings were fatal.
      CONCLUSION: There was a high rate of suicides attempt in young singles,
      predominantly female population. These data were the highest agricultural
      activity of the country that provide important information about the
      characteristics of poisoning at the city.

PMID- 16598328
TI  - The effect of season and Ramadan fasting on the onset of acute cholecystitis.
AB  - OBJECTIVE: To investigate whether Ramadan fasting and seasonal variation has any
      effect on the onset of acute cholecystitis. METHODS: A cross-sectional study was
      conducted in Faghihi and Namazee Hospitals between September 1999 to August 2004.
      All files of patients with definite diagnosis of gallstone induced acute
      cholecystitis were reviewed for age, gender, date and method of treatment in
      relation to seasons and Ramadan fasting month. For comparison, we used Shaaban
      months (prior months) and Shavval months (following months). RESULTS: Eight
      hundred and sixty-four files (32.7% male and 62.8% were female) with definite
      diagnosis of acute cholecystitis were reviewed. Mean age was 56.3 +/- 16.18
      years. The frequency of acute cholecystitis was higher in summer in comparison
      with other seasons. The difference in the frequency of acute cholecystitis in
      Ramadan in comparison with Shaaban and Shavval months was not considerable.
      CONCLUSION: Acute cholecystitis displays seasonal characteristics; however, this
      seasonal variability would be influenced by other unknown environmental and
      genetic factors. Ramadan fasting may not precipitate the onset of acute
      cholecystitis.

PMID- 16598329
TI  - Is early mortality related to timing of surgery after fracture femur in the
      elderly?
AB  - OBJECTIVE: The purpose of this study is to review the outcome of fracture femur
      in elderly patients (>65 years), and to identify cause or causes of mortality.
      METHODS: Between January 1996 and December 2002, 115 patients over 65 years were
      admitted and operated at King Fahd University Hospital, Al-Khobar. Fifty-six of
      patients suffered with femoral fractures. Demographic data collected included
      age, gender, site of fracture, co-morbidities, delay in surgery, duration of
      surgery, implant used and Anesthesia Society of America scoring (ASA). A minimum
      follow up of 12 months was considered important for inclusion in the study.
      Patients remained alive were assessed for their functional independence. RESULTS:
      The data of 48 patients were gathered for analysis. There were 31 males and 17
      females with a mean age of 76.5 years (age range 65-101 years). The mean follow
      up was 32.8 months (12-84 months +/- SD 17.81). There were 32 fractures of the
      trochanteric area. The average delay in surgery was 112 hours (24-280 hours). At
      the end of 24 months: 13 (27%) were dead and 28 (80%) were functionally
      independent similar to pre-injury status. There was statistical significance
      between the ASA score and the mortality (p<0.005). However, mortality
      significantly higher in patients who underwent surgery under general anesthesia
      p<0.05. CONCLUSION: Our data indicate that the mortality in the elderly is not
      related to the delay in surgery. The significant factors to early demise of
      patients were high ASA score, and the type of anesthesia used during surgery.

PMID- 16598330
TI  - Traditional beliefs as forgotten influencing factors on breast-feeding
      performance in Turkey.
AB  - OBJECTIVE: The aim of this cross-sectional study was to identify the infant
      feeding practices and to evaluate the attitudes and beliefs of mothers on breast
      feeding in Turkey. METHODS: This study was established in 10 provinces of Turkey
      between December 2000 and March 2001 and the study group was comprised of 1,767
      women between the ages of 15-49 years (mean 27.6 +/- 6.4 years). Questionnaires
      were self-filled by mothers in the waiting rooms of the health centers. RESULTS:
      One hundred seventy-three women (9.9%) were illiterate, 829 (47.7%) had < or =5
      years of schooling, and 83.4% were housewives. A significant number of women have
      traditional beliefs related to breast-feeding practices. According to 23.4% of
      the women at least 3 calls to prayer (average 12 hours) should be waited before
      the first breast-feeding postpartum and more than 30% of the mothers believe that
      colostrum should not be given to the newborn, some mothers breast milk could harm
      their babies, and an evil eye could harm their breast milk. The traditional
      belief status and educational status of the women differed significantly between
      provinces, lower educational status and higher rates of women with traditional
      beliefs were observed in less developed eastern provinces. Overall, 60.6% of the
      women were knowledgeable on breast-feeding practices, whereas only 13.5% were
      scored as good in attitudes. Among all women with breast-feed babies, 35.8%
      started supplementary feeding in the first 3 months of life. Mother's age,
      education, occupation and traditional beliefs did not have a significant effect
      on supplementation time. CONCLUSION: As a result, these findings suggest the
      importance of taking into account the customs, local beliefs and family
      influences in planning community health programs.

PMID- 16598331
TI  - Pregnancy outcomes after laparoscopic ovarian drilling in women with polycystic
      ovarian syndrome.
AB  - OBJECTIVE: To study whether there is an increased risk of glucose intolerance and
      hypertensive complications during pregnancy in women with polycystic ovarian
      syndrome (PCOS) who conceived after laparoscopic ovarian drilling and to
      investigate if there is an adverse pregnancy outcome. METHODS: This prospective
      study took place at Salmaniya Medical Complex in Bahrain, between June 1996 and
      June 2003. We compared the pregnancy and neonatal outcomes of 134 patients with
      PCOS who were treated with laparoscopic ovarian drilling with 479 pregnant women
      without PCOS (controls). We used the multiple logistic regression analysis to
      assess the risk of PCOS on impaired glucose tolerance (IGT), gestational diabetes
      mellitus (GDM), hypertensive disorders in pregnancy (HDP) and premature delivery.
      RESULTS: Subjects with PCOS had a significantly greater prepregnancy body mass
      index, prevalence of obesity and nulliparity as compared with controls. The
      incidence of IGT (p=0.007), GDM (p=0.01) and HDP (p=0.001) were significantly
      higher in pregnant PCOS compared with the control group. There were no
      significant differences in the neonatal outcomes and prevalence of premature
      delivery between the 2 study groups. When non-obese PCOS patients were compared
      with non-obese controls, the incidence of GDM (p=0.04) and HDP (p=0.004) were
      still significantly higher in the former. The prevalence of pregnancy
      complications were not significantly different when obese PCOS were compared with
      obese control patients. The PCOS was demonstrated as a risk factor for IGT
      (p=0.05), GDM (p=0.03) and HDP (p=0.03), but not for premature delivery.
      CONCLUSION: Women with PCOS who conceived after the drilling were at higher risk
      of IGT, GDM and HDP, and this risk seemed to be independent of maternal obesity.

PMID- 16598332
TI  - The handsearching of 2 medical journals of Bahrain for reports of randomized
      controlled trials.
AB  - OBJECTIVE: To identify reports of randomized trials by handsearching 2 Bahrain
      medical journals, which are indexed in the biomedical database EMBASE and to
      determine any added value of the handsearching by comparing the reports found by
      handsearching with what would have been found by searching EMBASE to examine (i)
      the precision and sensitivity of the EMBASE index term Randomized Controlled
      Trial (RCT) and (ii) The Cochrane Collaboration's systematic electronic search of
      EMBASE (which uses 4 index terms and 9 free-text terms). METHODS: All issues of
      the Bahrain Medical Bulletin (BMB) (1979-2004) and the Journal of the Bahrain
      Medical Society (JBMS) (1989-2004) were handsearched in February 2005 for reports
      of RCTs or Controlled Clinical Trials (CCTs), according to Cochrane eligibility
      criteria. RESULTS: Out of 395 articles in BMB we found reports of 12 RCTs and 4
      CCTs. Distribution by country of corresponding author: Jordan (4 RCTs, one CCT),
      Bahrain (one RCT, one CCT), India (3 RCTs, one CCT), Kuwait (one CCT), Saudi
      Arabia (2 RCTs), USA/Bahrain (one RCT), and Oman (one RCT); and by specialty:
      Anesthesia (8), Surgery (1) Pediatrics (1), Radiotherapy (1), Community Medicine
      (1), Sports Medicine (1), Obstetrics/Gynecology (3). The Journal of the Bahrain
      Medical Society included reports of 14 RCTs and 3 CCTs, out of 97 articles.
      Distribution by country of corresponding author: Jordan (9 RCTs, 2 CCTs), Bahrain
      (3 RCTs), Egypt (one RCT), Kuwait (one RCT), and Saudi Arabia (one RCT); and by
      specialty: Anesthesia (7), General Surgery (3), Obstetrics/Gynecology (1),
      Radiotherapy (1), Pediatrics (1), Orthopaedic Surgery (1), Education (1) Ear Nose
      and Throat (1) Ophthalmology (1). Overall, of the 33 reports of trials found by
      handsearching both journals, only 23 were included in EMBASE of which only 6 had
      been indexed with the term RCT. Of the 23 reports of trials included in EMBASE,
      16 had been identified in the Collaboration s systematic search of EMBASE. Two
      reports of trials could have been retrieved by this search but there was
      insufficient information in the title and abstract to code these as trials. The
      EMBASE records for the remaining 5 reports of trials did not contain terms
      currently used by The Cochrane Collaboration to identify reports of randomized
      trials in this database. CONCLUSION: The handsearching of these journals will
      help minimize publication bias by locating randomized trials not previously
      identified and, through their inclusion in the Cochrane Central Register of
      Controlled Trials (CENTRAL) in The Cochrane Library, will ensure reports of
      randomized trials will not remain buried through indexing bias.

PMID- 16598333
TI  - Leiomyosarcoma of the bladder in a 16-year-old girl with a history of
      cyclophosphamide therapy for bilateral retinoblastoma during infancy.
AB  - A 16-year-old female with bladder leiomyosarcoma had a history of bilateral
      retinoblastoma at 6 months of life. She received cyclophosphamide chemotherapy
      after surgical enucleation. In this report, we discussed the possible role of
      retinoblastoma or cyclophosphamide as a target for the development of bladder
      leiomyosarcoma.

PMID- 16598334
TI  - von Recklinghausen's neurofibromatosis associated with membranous
      glomerulonephritis.
AB  - A 70-year old woman, known case of von Recklinghausen's neurofibromatosis
      presented with nephrotic syndrome and mild azotemia. Renal biopsy revealed
      membranous nephropathy. After ruling out secondary causes of membranous
      nephropathy, a possible coexistence of von Recklinghausen's neurofibromatosis and
      membranous nephropathy were thought of. This association has rarely been
      reported.

PMID- 16598335
TI  - A rare case of distal one-third of the transverse colon supplied by a branch from
      splenic artery.
AB  - We observed a rare variation of splenic artery during the routine dissection in
      the Laboratory of the Anatomy Department. It arose from the splenic artery toward
      the distal part of transverse colon which typically supplied by the inferior
      mesenteric artery. Embryologically distal part of the transverse colon is a
      segment of hindgut. In this case, splenic artery which an artery of foregut
      supplies an area of hindgut. The knowledge of splenic artery variations has
      significant importance during surgery of the organs of the upper abdominal
      region. In this study, we discussed clinical significance and embryological
      aspects of this anomalous artery.

PMID- 16598336
TI  - Multicentric, synchronous giant-cell tumor of bone.
AB  - Multicentric giant cell tumor is a rare variant of giant cell tumor. In this
      case, we report a case of a 15-year-old female patient with synchronous type of
      multicentric giant cell tumor.

PMID- 16598338
TI  - Forgotten surgical sponge (gossy-piboma), removed 5 years later.

PMID- 16598337
TI  - Emergency cerclage. A successful challenge despite advanced second trimester
      cervical dilatation.
AB  - A 22-year-old, primigravida +/- 20 weeks of gestation presented with abdominal
      pain. She was diagnosed as a case of advanced cervical incompetence. We carried
      out an emergency cerclage after 24 hours from her admission, while the cervix was
      fully dilated with bulging of the membranes and prolapse of both lower limbs in
      the middle of the vagina. She delivered normally at 38 weeks of gestation with
      favorable outcomes. We believe that even if miscarriage is inevitable, the so
      called emergency cerclage might be considered.

PMID- 16598339
TI  - The interventricular septal giant hydatid cyst caused by biventricular outflow
      tract obstruction.

PMID- 16598340
TI  - Predictive value of thrombolysis in myocardial infarction risk score analysis for
      in-hospital and long term survival of patients with right ventricular infarction.

PMID- 16598341
TI  - An analysis of patients diagnosed with pulmonary embolism in terms of clinical
      and meteorological data.

PMID- 16598342
TI  - Busulfan induced myoclonus.

PMID- 16598343
TI  - Chlorambucil therapy in children with steroid-resistant nephrotic syndrome.

PMID- 16598344
TI  - Do C-reactive protein and procalcitonin predict hospital-acquired infection in
      patients with trauma?

PMID- 16598345
TI  - Scolicidal agents in hydatid cyst surgery.

PMID- 16598346
TI  - Tamoxifen effects on treatment fibrocystic breast disease in women.

PMID- 16598347
TI  - Family medicine in Turkey. Need for trainers in general practice.

PMID- 16598348
TI  - Assessment of the nutritional status of the elderly. Is ambiguity an aesthetic
      principle?

PMID- 16598349
TI  - The effect of breast milk and lanolin on sore nipples.

PMID- 16598355
TI  - The engineering of endovascular stent technology: a review.
AB  - The evolution of minimally invasive endovascular technology has initiated a
      significant paradigm shift in the treatment of vascular disease. A fundamental
      understanding of the science and engineering behind the technology of
      endovascular stents is a key to their appropriate implementation in practice.
      Furthermore, the rapid influx of new devices into the field requires
      practitioners to make their decisions on a foundation of the relative strengths
      and weaknesses of the various products. Although the principles of their use are
      not complex, the device design can have a profound effect on the device's
      functionality. Shape, thickness, coating, material selection, and imaging are
      just a few of the factors to consider in stent design. Subtle differences may
      have profound results. This review is designed to provide the reader with an
      overview of fundamental concepts that will aide the assessment of new technology.

PMID- 16598356
TI  - Open aneurysm repair in elderly patients not candidates for endovascular repair
      (EVAR): Comparison with patients undergoing EVAR or preferential open repair.
AB  - The authors reviewed a 2-year experience with abdominal aortic aneurysm (AAA)
      repair to determine if patients who were excluded from endovascular aneurysm
      repair (EVAR) because of anatomic criteria (Group III) represented a higher risk
      for subsequent open aneurysm repair than either patients undergoing EVAR (Group
      II) or those patients who preferentially underwent open repair (Group I). Between
      January 2001 and December 2003, 107 patients underwent AAA repair. Open repair
      was recommended in patients <70 years of age and without significant
      comorbidities (Group I). There were 35 patients in Group I; 72 patients were
      evaluated for EVAR; 29 patients underwent EVAR (Group II), and 43 were excluded
      and underwent open repair (Group III). Exclusion criteria were those recommended
      by the graft manufacturers. Patients in Group I were significantly younger than
      those in Groups II and III (p < 0.0001). Gender, incidence of diabetes, and
      hypertension were similar in all groups. Patients in Group III had a greater
      incidence of coronary artery disease (CAD) than those in Groups I and II,
      trending toward statistical significance (p = 0.06). Aneurysm size in Group II
      was statistically smaller than in Group I or III. Group III had significantly
      more complications (25.6% vs 5.7% and 6.9%) than either Group I or II (p <
      0.015). Cardiac complications were similar in all groups. Three patients in Group
      III required prolonged intubation and 3 in Group III developed renal
      insufficiency. A history of CAD was predictive of complications (21.8% vs 5.8%, p
      < 0.024), as was inclusion in Group III. There were 2 deaths in this series, both
      in Group III. Length of stay was significantly less in Group II (4.17 +/-2.36
      days) than in Group I (6.57 +/-1.84 days) or Group III (12.30 +/-9.82 days) (p =
      0.0001). Open aneurysm repair can be safely performed in younger good-risk
      patients (Group I) with results equivalent to EVAR (Group II) but with slightly
      longer length of stay (LOS). In older patients with suitable anatomy EVAR can be
      performed with minimal morbidity and short LOS. Older patients not suitable for
      EVAR (Group III) constitute a higher risk group of patients because of increased
      incidence of CAD and the need for more complex repairs. However, the mortality
      rate in this group was only 4.6%.

PMID- 16598357
TI  - Aorto uni-iliac modification of a bifurcated stent graft for endovascular
      aneurysm repair: Expanding the versatility of a modular device.
AB  - As endografting technology advances, anatomical constraints limiting access and
      deployment have become less of a burden. While unsuitable candidates for
      endografting exist, these patients are becoming less frequent. To broaden the
      applicability of endovascular abdominal aortic aneurysm repair (EVAR), we have
      modified the bifurcated AneuRx device into a unilimb modular prosthesis, by
      placing an aortic extender cuff across the flow divider, thus excluding its
      contralateral limb. This technique was used with success in 3 groups of patients:
      with occlusion of 1 iliac artery, with a nontraversable iliac stenosis, or with a
      small calcific aortic bifurcation. In these patients, anatomy can make it
      difficult, if not impossible, to place a bifurcated stent graft. Whether as a
      planned preoperative procedure or as a ;;bail-out'' maneuver, this procedure has
      been successful in avoiding open surgical conversion.

PMID- 16598358
TI  - Femoral pseudoaneurysms.
AB  - Iatrogenic pseudoaneurysms will continue to be a problem associated with arterial
      cannulation procedures. With the increasing trend toward minimally invasive
      procedures, vascular surgeons, as well as interventionalists will be performing
      more cannulation procedures; hence we will be more involved in the management of
      this complication more frequently. Treatment trends and efforts aimed at
      preventing iatrogenic pseudoaneurysms have evolved over the past decade. This
      article reviews the history and available literature on the subject, in
      conjunction with the experience of a center that performs over 10,000 cannulation
      procedures annually.

PMID- 16598359
TI  - Role of residual defects following carotid endarterectomy in the occurrence of
      cerebrovascular symptoms.
AB  - Carotid endarterectomy deals successfully with carotid atheromatous lesions, thus
      eliminating a potential source of cerebral emboli. At times, however, residual
      hemodynamic irregularities may occur as a result of technique imperfection or
      anatomic variations. These irregularities have been associated with a number of
      immediate and late postoperative complications, such as recurrent cerebrovascular
      symptoms and secondary episodes of stroke. For this reason, the detection of flow
      abnormalities or intimal defects in patients undergoing carotid endarterectomy
      and the achievement of normal intraoperative and postoperative hemodynamics are
      essential for the elimination of potentially life-threatening perioperative and
      late cerebrovascular events.

PMID- 16598360
TI  - Endovenous saphenous ablation corrects the hemodynamic abnormality in patients
      with CEAP clinical class 3-6 CVI due to superficial reflux.
AB  - This investigation was designed to determine whether minimally invasive
      radiofrequency or laser ablation of the saphenous vein corrects the hemodynamic
      impact and clinical symptoms of chronic venous insufficiency (CVI) in CEAP
      clinical class 3-6 patients with superficial venous reflux. Patients with CEAP
      clinical class 3-6 CVI were evaluated with duplex ultrasound and air
      plethysmography (APG) to determine anatomic and hemodynamic venous abnormalities.
      Patients with an abnormal (>2 mL/second) venous filling index (VFI) and
      superficial venous reflux were included in this study. Saphenous ablation was
      performed utilizing radiofrequency (RF) or endovenous laser treatment (EVLT).
      Patients were reexamined within 3 months of ablation with duplex to determine
      anatomic success of the procedure, and with repeat APG to determine the degree of
      hemodynamic improvement. Venous clinical severity scores (VCSS) were determined
      before and after saphenous ablation. Eighty-nine limbs in 80 patients were
      treated with radiofrequency ablation (RFA) (n = 58), or EVLT (n = 31). The
      average age of patients was 55 years and 66% were women. There were no
      significant differences in preoperative characteristics between the groups
      treated with RFA or EVLT. Postoperatively, 86% of limbs demonstrated near total
      closure of the saphenous vein to within 5 cm of the saphenofemoral junction.
      Eight percent remained open for 5-10 cm from the junction, and 6% demonstrated
      minimal or no saphenous ablation. The VFI improved significantly after ablation
      in both the RF and EVLT groups. Postablation, 78% of the 89 limbs were normal,
      with a VFI <2 mL/second, and 17% were moderately abnormal, between 2 and 4
      mL/second. VCSS scores (11.5 +/-4.5 preablation) decreased significantly after
      ablation to 4.4 +/-2.3. Minimally invasive saphenous ablation, using either RFA
      or EVLT, corrects or significantly improved the hemodynamic abnormality and
      clinical symptoms associated with superficial venous reflux in more than 90% of
      cases. These techniques are useful for treatment of patients with more severe
      clinical classes of superficial CVI.

PMID- 16598361
TI  - Prospective evaluation of combined upper and lower extremity DVT.
AB  - The clinical importance of upper extremity deep venous thrombosis (UEDVT) has
      been increasingly demonstrated in recent literature. Not only has the risk of
      pulmonary embolism from isolated upper extremity DVT been demonstrated, but a
      significant associated mortality has been encountered. Examination of this group
      of patients has demonstrated the existence of combined upper and lower extremity
      deep venous thrombosis (DVT) in some patients who exhibit an even higher
      associated mortality. As a result of this information, it has become the standard
      practice at this institution to search for lower extremity DVTs in patients found
      to have acute thrombosis of upper extremity veins. Since January 1999, there have
      been a total of 227 patients diagnosed with acute UEDVT. Within this group, 211
      (93%) patients had lower extremity studies; 45 of these 211 (21%) had acute lower
      extremity DVTs by duplex examination in addition to the upper extremity DVTs.
      Overall, there were 145 women, 66 men, and the average age was 70 +/-1.2 (SEM);
      22 of these patients had bilateral lower extremity thrombosis (LEDVT), and 8
      patients were found to have chronic thrombosis of lower extremity veins. Of the
      patients with bilateral upper extremity DVTs, there were 3 with bilateral LE
      acute DVTs. Finally, 8 of the remaining 166 patients (5%) with originally
      negative lower extremity studies were found to develop a thrombosis at a later
      date. These data serve to confirm previous studies, on a larger scale, that there
      should be a high index of suspicion in patients with UEDVT of a coexistent LEDVT.

PMID- 16598362
TI  - Total-contact casting as an adjunct to promote healing of pressure ulcers in
      amputees.
AB  - Partial foot amputations have become increasingly prevalent among long-lived
      diabetic patients. These patients have lower extremity neuropathy and are prone
      to ulceration at their amputation site. These ulcers are difficult to heal, and
      they place a significant financial and resource burden on the healthcare system.
      We examined the efficacy of total-contact casts (TCC) in diabetic amputees with
      nonhealing partial foot amputation site neuropathic ulcers. Data were collected
      retrospectively on all patients with amputations who were treated with a total
      contact cast between December 2000 and December 2003. Seventeen patients (13 men,
      4 women) with amputation site ulceration were identified. All patients were
      diagnosed with neuropathy secondary to diabetes and none had wound healing
      compromised by ischemia. The initial ulcer averaged 1,169 mm(2) with a depth of
      2.77 mm. Patients were treated with an average of 7.9 cast applications over 8.4
      weeks; 47% (8/17) of ulcers healed, but 29% (5/17) of patients were unable to
      complete their recommended treatment course secondary to complications from the
      TCC. Of the patients who were able to complete their treatment course, the
      healing rate was 66.7% (8/12). The recurrence rate for healed ulcers was 63%
      (5/8). Partial foot amputations with neuropathic ulcers present a very difficult
      problem to the vascular surgeon. Patient compliance and underlying medical
      comorbidities limit the success rate. In patients who can complete a TCC
      treatment course, good short term results can be expected. However, recurrence
      rates are high following discontinuation of mechanical TCC off-loading.

PMID- 16598363
TI  - Interventional techniques to facilitate supraaortic angioplasty and stenting.
AB  - Arterial occlusive disease involving the supra-aortic trunks (SATs) is relatively
      frequent. Its mere presence does not dictate the need for intervention.
      Revascularization options include intra and extrathoracic surgical bypasses and
      transpositions, and percutaneous endovascular approaches with angioplasty and
      stenting. This paper focuses on a description of the fundamental endovascular
      techniques and equipment that have proved useful in the senior author's (FJC) 15
      year experience with catheter-based intervention for treatment of SAT disease.
      These procedures have gained in popularity over the years and become the
      preferred modality for management of most patients today.

PMID- 16598364
TI  - Clamp before you cut: Proximal control of ruptured abdominal aortic aneurysms
      using endovascular balloon occlusion--Case reports.
AB  - While the mortality rate for elective abdominal aortic aneurysm (AAA) repair has
      declined over the last several decades, the rate for ruptured abdominal aortic
      aneurysm (RAAA) has unfortunately remained disturbingly high. Undiagnosed
      aneurysms may present with little warning until abdominal pain, syncope, and
      hypotension signify rupture. Fifty percent of patients with ruptured aneurysms
      die before reaching a medical facility, and their survival is highly dependent on
      hemodynamic stability at presentation. The degree of rupture containment and
      comorbid status of the patient determine hemodynamic stability. Endovascular
      stent grafting has significantly improved perioperative morbidity and mortality
      rates for elective AAA repair, and some of the same endovascular techniques can
      be used to obtain proximal control in patients presenting with RAAA. We describe
      3 consecutive cases of RAAA where proximal control was obtained using a
      percutaneously placed, transfemoral aortic occlusion balloon before induction of
      anesthesia.

PMID- 16598365
TI  - Surgical management of chronic mesenteric venous thrombosis--a case report.
AB  - Although mesenteric venous thrombosis is an uncommon disease, it is a diagnostic
      dilemma and if left untreated results in significant morbidity and mortality. The
      clinical presentation of mesenteric venous thrombosis (MVT) is varied and depends
      on the etiology. Prompt recognition and treatment is important as this may limit
      the progression of thrombosis. Even though medical management is the current
      mainstay of therapy, there have been reported cases of clinical improvement with
      operative management. The authors describe an improved outcome following
      mesenteric-systemic shunting in a symptomatic patient with acute-on-chronic MVT
      affecting the proximal superior mesenteric vein.

PMID- 16598366
TI  - Bilateral lower extremity gangrene requiring amputation associated with heparin
      induced thrombocytopenia--a case report.
AB  - Heparin use, both prophylactically and therapeutically, is prevalent among
      hospitalized patients. Patients on heparin may develop a thrombocytopenia that is
      self-limited. Fewer patients develop a heparin-induced thrombocytopenia that can
      cause severe bleeding and thrombosis owing to intravascular platelet aggregation.
      The authors present a case report of heparin-induced thrombocytopenia in a
      patient who underwent aortic arch and aortic valve replacement that resulted in
      bilateral above-knee amputations. The patient developed limb ischemia related to
      heparin-associated thrombosis, but had a delay in antibody seroconversion. Early
      and accurate diagnosis of heparin-induced thrombocytopenia requires a high
      clinical suspicion and may be present despite the absence of serum antibodies.

PMID- 16598367
TI  - Nutrition-related peptides and bone homeostasis.

PMID- 16598368
TI  - Childhood fractures are associated with decreased bone mass gain during puberty:
      an early marker of persistent bone fragility?
AB  - Whether peak bone mass is low among children with fractures remains uncertain. In
      a cohort of 125 girls followed over 8.5 years, 42 subjects reported 58 fractures.
      Among those, BMC gain at multiple sites and vertebral bone size at pubertal
      maturity were significantly decreased. Hence, childhood fractures may be markers
      of low peak bone mass acquisition and persistent skeletal fragility.
      INTRODUCTION: Fractures in childhood may result from a deficit in bone mass
      accrual during rapid longitudinal growth. Whether low bone mass persists beyond
      this period however remains unknown. MATERIALS AND METHODS: BMC at the spine,
      radius, hip, and femur diaphysis was prospectively measured over 8.5 years in 125
      girls using DXA. Differences in bone mass and size between girls with and without
      fractures were analyzed using nonparametric tests. The contribution of genetic
      factors was evaluated by mother-daughter correlations and that of calcium intake
      by Cox proportional hazard models. RESULTS: Fifty-eight fractures occurred in 42
      among 125 girls (cumulative incidence, 46.4%), one-half of all fractures
      affecting the forearm and wrist. Girls with and without fractures had similar
      age, height, weight. and calcium intake at all time-points. Before and during
      early puberty, BMC and width of the radius diaphysis was lower in the fracture
      compared with no-fracture group (p < 0.05), whereas aBMD and BMAD were similar in
      the two groups. At pubertal maturity (Tanner's stage 5, mean age +/- SD, 16.4 +/-
      0.5 years), BMC at the ultradistal radius (UD Rad.), femur trochanter, and lumbar
      spine (LS), and LS projected bone area were all significantly lower in girls with
      fractures. Throughout puberty, BMC gain at these sites was also decreased in the
      fracture group (LS, -8.0%, p = 0.015; UD Rad., -12.0%, p = 0.004; trochanter, 
      8.4%, p = 0.05 versus no fractures). BMC was highly correlated between prepuberty
      and pubertal maturity (R = 0.54-0.81) and between mature daughters and their
      mothers (R = 0.32-0.46). Calcium intake was not related to fracture risk.
      CONCLUSIONS: Girls with fractures have decreased bone mass gain in the axial and
      appendicular skeleton and reduced vertebral bone size when reaching pubertal
      maturity. Taken together with the evidence of tracking and heritability for BMC,
      these observations indicate that childhood fractures may be markers for low peak
      bone mass and persistent bone fragility.

PMID- 16598369
TI  - Infant growth influences proximal femoral geometry in adulthood.
AB  - The relationship between early growth and adult femoral geometry has not been
      studied previously. In 333 adults, we were able to show that infant weight
      predicts femoral width and cross-sectional moment of inertia but not femoral neck
      length. These results support the hypothesis that growth in early life leads to
      persisting differences in proximal femoral geometry. INTRODUCTION: Both femoral
      geometry and bone mass have been shown independently to predict both hip strength
      and fracture risk. Whereas growth during intrauterine and early postnatal life
      has been shown to influence adult bone mass, the relationship between growth in
      early life and adult femoral geometry has not been described previously.
      MATERIALS AND METHODS: We studied the relationship between growth during early
      life, adult hip geometry, and proximal femur bone mass in a sample of 333 men and
      women (60-75 years of age), for whom birth weight and weight at 1 year of age
      were recorded. Hip geometry was derived using Hip Structure Analysis software
      from proximal femur DXA scans (Hologic QDR 1000). RESULTS: There were significant
      (p < 0.002) relationships between weight at age 1 year and measures of femoral
      width as well as intertrochanteric (IT) cross-sectional moment of inertia (CSMI),
      but not with femoral neck length. The relationships with measures of femoral
      width but not CSMI remained after adjusting for adult body weight and were
      independent of proximal femoral BMC. CONCLUSIONS: These results support the
      hypothesis that different patterns of growth in utero and during the first year
      of life lead to persisting differences in proximal femoral geometry, thereby
      mediating in part the effects of early growth on risk of hip fracture in
      adulthood.

PMID- 16598370
TI  - Cellular activity on the seven surfaces of iliac bone: a histomorphometric study
      in children and adolescents.
AB  - Transiliac cortical bone histomorphometry was performed in 56 metabolic bone
      disease-free individuals 1.5-22.9 years of age. During the growing years, the two
      cortices of an iliac bone specimen differ with regard to bone cell activity on
      their surfaces, probably reflecting a modeling drift. INTRODUCTION: Standard bone
      histomorphometry in the clinical setting is typically limited to the analysis of
      cancellous bone. However, during the growth period, important changes occur also
      in the cortical compartment. MATERIALS AND METHODS: Transiliac bone samples from
      56 individuals between 1.5 and 22.9 years of age (25 male; tetracycline labeling
      present in 42 subjects) and without evidence of metabolic bone disease were
      analyzed. Each of the three bone surface types (periosteal, intracortical,
      endocortical) of each cortex was evaluated separately. Results were expressed
      relative to those obtained in trabecular bone. RESULTS: A significant increase in
      cortical width with age was detected only for the internal cortex. Porosity of
      the external cortex was highest in the 7- to 10.9-year age group and decreased
      thereafter, whereas there was no clear trend with age for the porosity of the
      internal cortex. Intracortical remodeling activity decreased after 14 years of
      age. Periosteal bone formation was very active until 13 years of age, but was
      close to zero in subjects above that age. As to endocortical surfaces, all bone
      surface-based parameters of bone formation were higher on the internal cortex
      than on the external cortex, whereas bone resorption parameters were higher on
      the external cortex. CONCLUSIONS: In growing subjects, the two cortices of an
      iliac bone specimen differ with regard to bone cell activity on their surfaces.
      These data raise fundamental questions about the regulation of bone cell activity
      in children and adolescents.

PMID- 16598371
TI  - Increased prevalence of radiological spinal deformities in adult patients with GH
      deficiency: influence of GH replacement therapy.
AB  - This cross-sectional study shows that a high number of untreated adult patients
      with GHD develop radiological vertebral deformities. Patients undergoing GH
      replacement treatment showed a significantly lower prevalence of vertebral
      deformities versus treated patients in the presence of similar BMD, as assessed
      by DXA. INTRODUCTION: In this cross-sectional study, we investigated whether the
      prevalence and degree of spinal deformities in adults with growth hormone
      deficiency (GHD) were related to the age of patients, degree of bone turnover,
      BMD, and recombinant human GH (rhGH) replacement therapy. MATERIALS AND METHODS:
      One hundred seven adult hypopituitary patients (67 males and 40 females; mean
      age, 47 years; range: 16-81 years) with severe GHD and 130 control subjects (39
      males, 91 females; mean age: 58.9 years; range: 26-82 years) were evaluated for
      BMD (DXA) and vertebral deformities (quantitative morphometric analysis). At
      study entry, 65 patients were on replacement therapy with rhGH, whereas 42
      patients had never undergone rhGH. RESULTS: Vertebral fractures were
      significantly more frequent in GHD patients versus control subjects (63.6% versus
      37.7%; chi2 15.7; p < 0.001). The fracture prevalence, as well as the fracture
      number, was significantly higher in untreated versus treated patients (78.6%
      versus 53.8%; chi2: 6.7; p = 0.009), although the two groups of patients did not
      show any significant difference in median T score. In untreated GHD patients, the
      prevalence of vertebral deformities was correlated with T score (p = 0.002) and
      duration of disease (p = 0.003). In treated GHD patients, the prevalence of
      spinal deformities was correlated only with the timing of the beginning of rhGH
      replacement. CONCLUSIONS: This cross-sectional study reports high prevalence of
      vertebral radiological deformities in adult patients with untreated GHD. The
      replacement treatment of GHD leads to a significant decrease in fracture rate.

PMID- 16598372
TI  - Free testosterone is an independent predictor of BMD and prevalent fractures in
      elderly men: MrOS Sweden.
AB  - The role of androgens for bone health in elderly men is unclear. We show that
      free testosterone within the normal range is a predictor of BMD at predominantly
      cortical bone sites and of previous osteoporosis-related fractures in elderly
      Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major
      health concern not only in women but also in men. Previous studies have clearly
      shown that serum levels of estradiol are associated with BMD, whereas more
      conflicting data have been presented regarding the predictive value of
      testosterone (T) for bone health in elderly men. The aim of this study was to
      investigate if serum levels of T are associated with BMD and/or prevalent
      fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish
      part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were
      measured using DXA, and prevalent fractures were recorded using standardized
      questionnaires and by vertebral X-ray analyses. Serum levels of total T, total
      estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by
      radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass
      action equations. Height, weight, age, physical activity, smoking habits, and
      calcium intake were included together with FT and FE2 in regression models for
      BMD. RESULTS: FT was an independent positive predictor of BMD in total body,
      total hip, femur trochanter, and arm but not in the lumbar spine. The highest
      independent predictive value of FT was found in the arm and the hip (with a
      relatively high content of cortical bone). FE2 was an independent predictor of
      BMD at all bone sites studied, and the highest predictive value was seen for
      lumbar spine (with relatively high content of trabecular bone) BMD. FT but not
      FE2 was a positive predictor of total body bone area and BMC. FT levels below the
      median were independent predictors of prevalent osteoporosis-related fractures
      (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures
      (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for
      prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These
      findings show that variation of FT within the normal range is an independent but
      modest predictor of BMD at predominantly cortical bone sites and of previous
      osteoporosis-related fractures in elderly men. Our data indicate that not only
      estrogens but also androgens are of importance for bone health in elderly men.
      Longitudinal studies investigating the predictive value of T for fracture risk in
      elderly men are required.

PMID- 16598373
TI  - Vertebral fracture risk reduction with strontium ranelate in women with
      postmenopausal osteoporosis is independent of baseline risk factors.
AB  - Strontium ranelate (2 g/day) was studied in 5082 postmenopausal women. A
      reduction in incident vertebral fracture risk by 40% was shown after 3 years.
      This effect was independent of age, initial BMD, and prevalent vertebral
      fractures. INTRODUCTION: Strontium ranelate is an orally active treatment able to
      decrease the risk of vertebral and hip fractures in osteoporotic postmenopausal
      women. The aim of this study was to assess the efficacy of strontium ranelate
      according to the main determinants of vertebral fracture risk: age, baseline BMD,
      prevalent fractures, family history of osteoporosis, baseline BMI, and addiction
      to smoking. MATERIALS AND METHODS: We pooled data of two large multinational
      randomized double-blind studies with a population of 5082 (2536 receiving
      strontium ranelate 2 g/day and 2546 receiving a placebo), 74 years of age on
      average, and a 3-year follow-up. An intention-to-treat principle was used, as
      well as a Cox model for comparison and relative risks. RESULTS: The treatment
      decreased the risk of both vertebral (relative risk [RR] = 0.60 [0.53-0.69] p <
      0.001) and nonvertebral (RR = 0.85 [0.74-0.99] p = 0.03) fractures. The decrease
      in risk of vertebral fractures was 37% (p = 0.003) in women <70 years, 42% (p <
      0.001) for those 70-80 years of age, and 32% (p = 0.013) for those > or = 80
      years. The RR of vertebral fracture was 0.28 (0.07-0.99) in osteopenic and 0.61
      (0.53-0.70) in osteoporotic women, and baseline BMD was not a determinant of
      efficacy. The incidence of vertebral fractures in the placebo group increased
      with the number of prevalent vertebral fractures, but this was not a determinant
      of the effect of strontium ranelate. In 2605 patients, the risk of experiencing a
      first vertebral fracture was reduced by 48% (p < 0.001). The risk of experiencing
      a second vertebral fracture was reduced by 45% (p < 0.001; 1100 patients).
      Moreover, the risk of experiencing more than two vertebral fractures was reduced
      by 33% (p < 0.001; 1365 patients). Family history of osteoporosis, baseline BMI,
      and addiction to smoking were not determinants of efficacy. CONCLUSIONS: This
      study shows that a 3-year treatment with strontium ranelate leads to
      antivertebral fracture efficacy in postmenopausal women independently of baseline
      osteoporotic risk factors.

PMID- 16598374
TI  - Cortical pQCT measures are associated with fractures in dialysis patients.
AB  - To determine if pQCT could identify HD patients with fractures, we conducted a
      cross-sectional study in 52 men and women on HD. We found that cortical, but not
      trabecular, pQCT measures were associated with fractures. INTRODUCTION: Fractures
      are common in hemodialysis (HD) patients, yet DXA is inconsistently associated
      with fractures. One explanation for this lack of association may be that HD
      patients have a selective decrease in cortical density not identified by standard
      DXA. MATERIALS AND METHODS: We used pQCT to examine cross-sectional associations
      between cortical and trabecular measures and fractures in 36 men and 16 women, >
      or = 50 years of age, on HD for at least 1 year. We confirmed low-trauma nonspine
      fractures since starting HD. Prevalent vertebral fractures were identified by
      morphometry of lateral spine X-rays. pQCT measurements of the nondominant radius
      included trabecular density, cortical density, total area, cortical area, and
      cortical thickness. We also obtained DXA measurements of the hip and lumbar
      spine. We used logistic regression models, adjusted for age, weight, and sex, to
      examine the association between fracture (vertebral and/or self-reported
      nonspine) and each pQCT measure. Results are reported as ORs per SD decrease in
      the independent variable. RESULTS: The mean age was 65.8 +/- 9.0 (SD) years, the
      mean weight was 72.3 +/- 15.6 kg, most (32 of 52) subjects were white, and there
      were 32 fractures in 27 subjects (prevalent vertebral fracture or low-trauma
      fracture) since starting dialysis. A decrease in cortical density was associated
      with fractures (OR = 16.67; 95% CI: 2.94-83.33), as was a decrease in cortical
      area (OR = 3.04; 95% CI: 1.28-7.25) and a decrease in cortical thickness (OR =
      3.26; 95% CI: 1.36-7.87). Fractures were not associated with pQCT trabecular
      density (OR = 1.18; 95% CI: 0.6-2.33), total area (OR = 1.1; 95% CI: 0.59-1.7),
      or DXA measurements of the hip and spine. CONCLUSIONS: Cortical parameters of the
      radius were associated with fractures in HD patients. If confirmed in prospective
      studies, these findings may explain the lack of association between fracture and
      standard DXA measurements and raise the possibility that pQCT could be used to
      identify HD patients at high risk of fracture.

PMID- 16598375
TI  - High bone turnover is an independent predictor of mortality in the frail elderly.
AB  - Osteoporotic fractures are associated with accelerated bone turnover and excess
      mortality. In a prospective study of 1112 frail subjects (79% female; mean age,
      86 years), high bone turnover was an independent predictor of all-cause
      mortality. This association seemed to be mainly manifested in deaths from
      cardiovascular causes. INTRODUCTION: Osteoporotic fractures are associated with
      accelerated bone turnover and excess mortality. In a prospective cohort study of
      elderly men and women, we assessed whether the rate of bone turnover measured by
      markers of bone remodeling is a direct predictor of mortality. MATERIALS AND
      METHODS: We measured serum concentrations of the aminoterminal propeptide of type
      I collagen (PINP), a marker of bone formation, and of the carboxyterminal
      telopeptide of type I collagen (CTX-I), a marker of bone resorption, along with
      serum PTH and 25-hydroxyvitamin D [25(OH)D] levels in 1112 subjects (79% female;
      mean age, 86 years) living in residential care. Co-morbidity was measured using
      the Implicit Illness Severity Scale. Fracture data were validated by a radiology
      report. Mortality and causes of death were ascertained from death certificates.
      RESULTS: Over a median follow-up of 817 days, 559 (50.3%) subjects died. In
      univariate analyses, time to death from all causes was significantly (p < 0.01)
      associated with age (HR = 1.62 per 10 years), male sex (HR = 1.33), immobility
      (HR = 1.94), co-morbidity (HR = 0.31, mild versus severe), lower weight (HR =
      0.83 per 10-kg increase), impaired cognitive function (HR = 2.14, severe versus
      normal), number of medications (HR = 1.05 each), hip fracture (HR = 2.26), log
      serum creatinine (HR = 1.67), log PTH (HR = 1.29), CTX-I (HR = 1.70, highest 25%
      versus lowest 75%), and PINP (HR = 1.46, highest 25% versus lowest 75%). In
      multivariate analysis adjusting for age, sex, immobility, co-morbidity, weight,
      cognitive function, number of medications, PTH, and hip fracture status, the
      highest quartile was significantly more likely to die than the rest for both
      serum CTX-I (HR = 1.39; 95% CI: 1.14-1.70; p = 0.002) and PINP (HR = 1.25; 95%
      CI: 1.02-1.52; p = 0.03). For individual causes of death, CTX-I was significantly
      associated with deaths from cardiac causes (HR = 1.78: 95% CI: 1.27-2.50; p <
      0.001). CONCLUSIONS: We conclude that in the frail elderly, high bone turnover is
      associated with all cause mortality independently of age, sex, health status,
      serum PTH levels, and hip fracture status. The mechanism of the effect of bone
      turnover on mortality seems to be mainly manifested in deaths from cardiovascular
      causes.

PMID- 16598376
TI  - Human ALOX12, but not ALOX15, is associated with BMD in white men and women.
AB  - The Alox15 gene was recently identified as a negative regulator of peak BMD in
      mice. Polymorphisms in human ALOX12, but not ALOX15, were significantly
      associated with spine BMD in white men and women, suggesting that ALOX12 may
      contribute to normal variation in BMD. INTRODUCTION: Osteoporosis is a complex
      disease with both genetic and environmental risk factors. A major determinant of
      osteoporosis is peak BMD, which is a highly heritable trait. Recently, the
      arachidonate 15-lipoxygenase (Alox15) gene was identified as a negative regulator
      of peak BMD in mice. MATERIALS AND METHODS: To assess the contribution of
      lipoxygenase genes to normal BMD variation in healthy white men and women, we
      performed population- and family-based association studies of two arachidonate
      lipoxygenase genes: ALOX15, which is the human homolog of mouse Alox15, and
      ALOX12, which is functionally similar to Alox15. Single nucleotide polymorphisms
      (SNPs) distributed across the two genes were genotyped. BMD was measured at the
      femoral neck and lumbar spine in 411 men 18-61 years of age and 1291
      premenopausal women 20-50 years of age. RESULTS: Moderate evidence of association
      was found between spine BMD and six SNPs in the ALOX12 gene in both men and women
      (p = 0.0052-0.050). Furthermore, the most common SNP haplotype in ALOX12 showed
      evidence of significant association with high spine BMD in men (p = 0.0083),
      whereas the second most common haplotype was associated with high spine BMD in
      women (p = 0.0081). CONCLUSIONS: Polymorphisms in the ALOX12 gene may contribute
      to normal variation in spine BMD.

PMID- 16598377
TI  - A nonprostanoid EP4 receptor selective prostaglandin E2 agonist restores bone
      mass and strength in aged, ovariectomized rats.
AB  - CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin
      E2 agonist. CP432 stimulates trabecular and cortical bone formation and restores
      bone mass and bone strength in aged ovariectomized rats with established
      osteopenia. INTRODUCTION: The purpose of this study was to determine whether a
      newly discovered, nonprostanoid EP4 receptor selective prostaglandin E2 (PGE2)
      agonist, CP432, could produce bone anabolic effects in aged, ovariectomized (OVX)
      rats with established osteopenia. MATERIALS AND METHODS: CP432 at 0.3, 1, or 3
      mg/kg/day was given for 6 weeks by subcutaneous injection to 12-month-old rats
      that had been OVX for 8.5 months. The effects on bone mass, bone formation, bone
      resorption, and bone strength were determined. RESULTS: Total femoral BMD
      increased significantly in OVX rats treated with CP432 at all doses. CP432
      completely restored trabecular bone volume of the third lumbar vertebral body
      accompanied with a dose-dependent decrease in osteoclast number and osteoclast
      surface and a dose-dependent increase in mineralizing surface, mineral apposition
      rate, and bone formation rate-tissue reference in OVX rats. CP432 at 1 and 3
      mg/kg/day significantly increased total tissue area, cortical bone area, and
      periosteal and endocortical bone formation in the tibial shafts compared with
      both sham and OVX controls. CP432 at all doses significantly and dose-dependently
      increased ultimate strength in the fifth lumber vertebral body compared with both
      sham and OVX controls. At 1 and 3 mg/kg/day, CP432 significantly increased
      maximal load in a three-point bending test of femoral shaft compared with both
      sham and OVX controls. CONCLUSIONS: CP432 completely restored trabecular and
      cortical bone mass and strength in established osteopenic, aged OVX rats by
      stimulating bone formation and inhibiting bone resorption on trabecular and
      cortical surfaces.

PMID- 16598378
TI  - Relative impact of androgen and estrogen receptor activation in the effects of
      androgens on trabecular and cortical bone in growing male mice: a study in the
      androgen receptor knockout mouse model.
AB  - The relative importance of AR and ER activation has been studied in pubertal male
      AR knockout and WT mice after orchidectomy and androgen replacement therapy,
      either with or without an aromatase inhibitor. AR activation dominates normal
      trabecular bone development and cortical bone modeling in male mice. Moreover,
      optimal periosteal bone expansion is only observed in the presence of both AR and
      ER activation. INTRODUCTION: Androgen receptor (AR)-mediated androgen action has
      traditionally been considered a key determinant of male skeletal growth.
      Increasing evidence, however, suggests that estrogens are also essential for
      normal male bone growth. Therefore, the relative importance of AR-mediated and
      estrogen receptor (ER)-mediated androgen action after aromatization remains to be
      clarified. MATERIALS AND METHODS: Trabecular and cortical bone was studied in
      intact or orchidectomized pubertal AR knockout (ARKO) and male wildtype (WT)
      mice, with or without replacement therapy (3-8 weeks of age). Nonaromatizable
      (dihydrotestosterone [DHT]) and aromatizable (testosterone [T]) androgens and T
      plus an aromatase inhibitor (anastrazole) were administered to orchidectomized
      ARKO and WT mice. Trabecular and cortical bone modeling were evaluated by static
      and dynamic histomorphometry, respectively. RESULTS: AR inactivation or
      orchidectomy induced a similar degree of trabecular bone loss (-68% and -71%,
      respectively). Both DHT and T prevented orchidectomy-induced bone loss in WT mice
      but not in ARKO mice. Administration of an aromatase inhibitor did not affect T
      action on trabecular bone. AR inactivation and orchidectomy had similar negative
      effects on cortical thickness (-13% and -8%, respectively) and periosteal bone
      formation (-50% and -26%, respectively). In orchidectomized WT mice, both DHT and
      T were found to stimulate periosteal bone formation and, as a result, to increase
      cortical thickness. In contrast, the periosteum of ARKO mice remained
      unresponsive to either DHT or T. Interestingly, administration of an aromatase
      inhibitor partly reduced T action on periosteal bone formation in orchidectomized
      WT mice (-34% versus orchidectomized WT mice on T), but not in ARKO mice. This
      effect was associated with a significant decrease in serum IGF-I (-21% versus
      orchidectomized WT mice on T). CONCLUSIONS: These findings suggest a major role
      for AR activation in normal development of trabecular bone and periosteal bone
      growth in male mice. Moreover, optimal stimulation of periosteal growth is only
      obtained in the presence of both AR and ER activation.

PMID- 16598379
TI  - Importance of individual rods and plates in the assessment of bone quality and
      their contribution to bone stiffness.
AB  - Local morphometry based on the assessment of individual rods and plates was
      applied to 42 human vertebral trabecular bone samples. Results showed that
      multiple linear regression models based on local morphometry as a measure for
      bone microstructure helped improving our understanding of the role of local
      structural changes in the determination of bone stiffness as assessed from direct
      and computational biomechanics. INTRODUCTION: In a recent study, we proposed a
      method for local morphometry of trabecular bone, i.e., morphometry as applied to
      individual rods and plates. In this study, we used this method to study the
      relative importance of local morphometry in the assessment of bone architecture
      and its relative contribution to the stiffness of human vertebral bone. MATERIALS
      AND METHODS: We extracted 42 human trabecular bone autopsies from nine intact
      spinal columns. The cylindrical samples were imaged with muCT to assess bone
      microstructure. From these images, global and local morphometric indices were
      derived and related to Young's modulus as assessed by experimental uniaxial
      compression testing (Emeas) and computational finite element analysis (EFE).
      RESULTS: We found the best single predictor for Young's modulus to be apparent
      bone volume density (BV/TV), which explained 89% of the variance in EFE when
      fitted with a power law. A multiple linear regression model combining mean
      trabecular spacing (Tb.Sp), mean slenderness of the rods (<Ro.Sl>), and the
      relative amount of rod volume to total bone volume (Ro.BV/BV) was able to explain
      90% of the variance in EFE. This model could not be improved by adding BV/TV as
      an independent variable. Furthermore, we found that mean trabecular thickness of
      the rods was significantly related to EFE (r2 = 0.42), whereas mean trabecular
      thickness of plates had no correlation to Young's modulus. Because the globally
      determined trabecular thickness does not discriminate between rods and plates,
      this index had only a poor predictive power for EFE (r2 = 0.09), showing the
      importance of local analysis of individual rods and plates. CONCLUSIONS: From
      these results, we conclude that models based on local morphometry help improving
      our understanding of the relative importance of local structural changes in the
      determination of the stiffness of bone. Separate analysis of individual rods and
      plates may help to better predict age and disease-related fractures as well as to
      shed new light on the effect of pharmaceutical intervention in the prevention of
      such fractures beyond BMD.

PMID- 16598380
TI  - Reduced expression of thrombospondins and craniofacial dysmorphism in mice
      overexpressing Fra1.
AB  - Fra1 transgenic (Tg) mice develop osteosclerosis and exhibit altered expression
      of bone matrix proteins. We found that expression of Thbs1 and Thbs2 was reduced
      in Fra1 Tg osteoblasts. Fra1 Tg and non-osteosclerotic Thbs1-/-Thbs2-/- mice
      share an edge-to-edge bite. Therefore, reduced expression of thrombospondins may
      contribute to craniofacial dysmorphism independently of osteosclerosis.
      INTRODUCTION: Tg mice overexpressing Fra1, a component of the transcription
      factor activator protein-1 (AP-1), show progressive osteosclerosis caused by cell
      autonomous abnormalities in osteoblasts. The expression of several bone matrix
      proteins, including matrix gla protein, is dysregulated in Fra1 Tg osteoblasts.
      MATERIALS AND METHODS: In osteoblastogenic cultures, altered bone matrix
      production by Fra1 overexpression was monitored using Alizarin red staining,
      quantitative RT-PCR, and Western blotting. Responsiveness to ovariectomy was
      examined by bone histomorphometry. Craniofacial parameters were measured on
      radiographs and using CT. RESULTS: Thrombospondin-1 (Thbs1) and thrombospondin-2
      (Thbs2) were reduced in Fra1 Tg osteoblasts differentiated in vitro and in bones
      from Fra1 Tg mice. Despite alterations in bone matrix proteins, ovariectomy
      induces high turnover bone loss in Fra1 Tg mice as in wildtype mice. Fra1 Tg
      mice, as well as Thbs1-/- Thbs2-/- mice, which do not show osteosclerosis,
      exhibit an edge-to-edge bite phenotype associated with craniofacial dysmorphism.
      CONCLUSIONS: These data suggest that reduced expression of thrombospondins in
      Fra1 Tg mice underlies craniofacial dysmorphism, independent of osteosclerosis.

PMID- 16598381
TI  - Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast
      recruitment and bone loss.
AB  - Mechanical stimulation of cultured osteocytic cells attenuates their apoptosis.
      We report here that, conversely, reduced mechanical forces in the murine model of
      unloading by tail suspension increases the prevalence of osteocyte apoptosis,
      followed by bone resorption and loss of mineral and strength. INTRODUCTION:
      Mechanical loading is critical for the maintenance of bone mass; weightlessness,
      as with reduced physical activity in old age, bed rest, or space flight,
      invariably leads to bone loss. However, the cellular and molecular mechanisms
      responsible for these phenomena are poorly understood. Based on our earlier
      findings that physiologic levels of mechanical strain prevent apoptosis of
      osteocytic cells in vitro, we examined here whether, conversely, reduced
      mechanical forces increase the prevalence of osteocyte apoptosis in vivo and
      whether this event is linked to bone loss. MATERIALS AND METHODS: Swiss Webster
      mice or OG2-11beta-hydroxysteroid dehydrogenase type 2 (OG2-11beta-HSD2)
      transgenic mice and wildtype littermates were tail-suspended or kept under
      ambulatory conditions. Static and dynamic histomorphometry and osteocyte and
      osteoblast apoptosis by in situ end-labeling (ISEL) were assessed in lumbar
      vertebra; spinal BMD was measured by DXA; and bone strength was measured by
      vertebral compression. RESULTS: We show that within 3 days of tail suspension,
      mice exhibited an increased incidence of osteocyte apoptosis in both trabecular
      and cortical bone. This change was followed 2 weeks later by increased osteoclast
      number and cortical porosity, reduced trabecular and cortical width, and
      decreased spinal BMD and vertebral strength. Importantly, whereas in ambulatory
      animals, apoptotic osteocytes were randomly distributed, in unloaded mice,
      apoptotic osteocytes were preferentially sequestered in endosteal cortical bone-
      the site that was subsequently resorbed. The effect of unloading on osteocyte
      apoptosis and bone resorption was reproduced in transgenic mice in which
      osteocytes are refractory to glucocorticoid action, indicating that stress
      induced hypercortisolemia cannot account for these effects. CONCLUSIONS: We
      conclude that diminished mechanical forces eliminate signals that maintain
      osteocyte viability, thereby leading to apoptosis. Dying osteocytes in turn
      become the beacons for osteoclast recruitment to the vicinity and the resulting
      increase in bone resorption and bone loss.

PMID- 16598382
TI  - Bone marrow cell differentiation induced by mechanically damaged osteocytes in 3D
      gel-embedded culture.
AB  - Osteocytes are suggested to have a crucial role in the initial resorptive phase
      of bone turnover after microdamage. To study the role of osteocytes in targeted
      remodeling, we developed an in vitro model, in which osteocytes can be locally
      damaged and their interactions with bone marrow cells studied. Our results show
      that the damaged osteocytes activate the osteoclast precursors by soluble factors
      and thus can control the initial phase of targeted remodeling. INTRODUCTION:
      Microdamage in bone contributes to fractures and acts as a stimulus for bone
      remodeling. Besides the targeted remodeling, some remodeling may also be random
      to serve metabolic purposes. Osteocytes have been considered to provide a crucial
      role in the activation of osteoclastic bone resorption adjacent to the damaged
      site. This study was aimed to develop a relevant in vitro model of the targeted
      remodeling and to show that damaged osteocytes can induce the initial bone
      resorptive stage. MATERIALS AND METHODS: We developed a new device, in which
      osteocyte-like cell line MLO-Y4 cells were 3D cultured, subjected to local
      scratching, and assayed for cell viability. NIH3T3-3 cells were used as a
      control. Bone marrow cells were cultured on the top of the mechanically damaged
      MLO-Y4 cells, and the formation of TRACP+ cells was assayed. Additionally, the
      conditioned medium from scratched cultures was added to bone marrow cultures, and
      the TRACP activity in cell lysates was quantified. The macrophage-colony
      stimulating factor (M-CSF) and RANKL secretion in the conditioned medium was
      assayed by ELISA. RESULTS: Scratching induced the death of MLO-Y4 cells. When
      bone marrow cells were cultured over the gel-embedded MLO-Y4 cells, the
      application of mechanical scratching induced TRACP+ cell differentiation on gel
      surface. The cells with TRACP+ could be observed in the very restricted region
      along the scratching path. Additionally, mechanically damaged osteocytes secreted
      M-CSF and RANKL, and the conditioned medium showed the potential to induce TRACP+
      cells in bone marrow culture. CONCLUSIONS: These findings indicate that soluble
      factors secreted from damaged osteocytes can locally induce and activate the
      initial phase of osteoclastic cell formation. This study directly shows the
      association between the damaged osteocytes and the initiation of resorptive stage
      in bone remodeling.

PMID- 16598383
TI  - Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in
      the presence or absence of TGF-beta signaling.
AB  - A novel role for IGF-I in MSC chondrogenesis was determined. IGF-I effects were
      evaluated in the presence or absence of TGF-beta signaling by conditionally
      inactivating the TGF-beta type II receptor. We found that IGF-I had potent
      chondroinductive actions on MSCs. IGF-I effects were independent from and
      additive to TGF-beta. INTRODUCTION: Mesenchymal stem cells (MSCs) can be isolated
      from adult bone marrow (BM), expanded, and differentiated into several cell
      types, including chondrocytes. The role of IGF-I in the chondrogenic potential of
      MSCs is poorly understood. TGF-beta induces MSC chondrogenic differentiation,
      although its actions are not well defined. The aim of our study was to define the
      biological role of IGF-I on proliferation, chondrogenic condensation, apoptosis,
      and differentiation of MSCs into chondrocytes, alone or in combination with TGF
      beta and in the presence or absence of TGF-beta signaling. MATERIALS AND METHODS:
      Mononuclear adherent stem cells were isolated from mouse BM. Chondrogenic
      differentiation was induced by culturing high-density MSC pellets in serum- and
      insulin-free defined medium up to 7 days, with or without IGF-I and/or TGF-beta.
      We measured thymidine incorporation and stained 2-day-old pellets with TUNEL,
      cleaved caspase-3, peanut-agglutinin, and N-cadherin. Seven-day-old pellets were
      measured in size, stained for proteoglycan synthesis, and analyzed for the
      expression of collagen II and Sox-9 by quantitative real time PCR. We obtained
      MSCs from mice in which green fluorescent protein (GFP) was under the Collagen2
      promoter and determined GFP expression by confocal microscopy. We conditionally
      inactivated the TGF-beta type II receptor (TbetaRII) in MSCs using a cre-lox
      system, generating TbetaRII knockout MSCs (RIIKO-MSCs). RESULTS AND CONCLUSIONS:
      IGF-I modulated MSC chondrogenesis by stimulating proliferation, regulating cell
      apoptosis, and inducing expression of chondrocyte markers. IGF-I chondroinductive
      actions were equally potent to TGF-beta1, and the two growth factors had additive
      effects. Using RIIKO-MSCs, we showed that IGF-I chondrogenic actions are
      independent from the TGF-beta signaling. We found that the extracellular signal
      related kinase 1/2 mitogen-activated protein kinase (Erk1/2 MAPK) pathway
      mediated the TGF-beta1 mitogenic response and in part the IGF-I proliferative
      action. Our data, by showing the role of IGF-I and TGF-beta1 in the critical
      steps of MSC chondrogenesis, provide critical information to optimize the
      therapeutic use of MSCs in cartilage disorders.

PMID- 16598385
TI  - Effect of monoterpenes on the formation and activation of osteoclasts in vitro.
AB  - Monoterpenes, present in aromatic plants, are known to inhibit bone resorption in
      vivo. In this in vitro study, they inhibited the activation of osteoclasts only
      at high concentrations but inhibited the formation at much lower concentrations.
      Therefore, monoterpenes may act in vivo directly on osteoclastogenesis.
      INTRODUCTION: Monoterpenes are the major components of essential oils, which are
      formed in many plants. Typically, they are found in herbs and certain fruits.
      When fed to rats, they inhibit bone resorption by an unknown mechanism. In this
      study, their effect on the activity and formation of osteoclasts in vitro was
      studied. MATERIALS AND METHODS: The effect of monoterpenes on the development of
      osteoclasts was studied in co-cultures of bone marrow cells and osteoblasts and
      in cultures of spleen cells grown with colony stimulating factor (CSF)-1 and
      RANKL. In cultures of primary osteoblasts, alkaline phosphatase activity and
      levels of mRNA encoding RANKL and osteoprotegerin (OPG) mRNA (RT-PCR), and in
      osteoblast and spleen cell cultures, lactate dehydrogenase activity, a measure of
      toxicity, were determined. The activity of isolated rat osteoclasts was
      determined by counting the osteoclasts with actin rings using histofluorometry.
      RESULTS: The monoterpenes inhibited the formation of osteoclasts more strongly in
      co-cultures (> or = 1 microM) than in cultures of spleen cells (> or = 10
      microM). They had a minor effect on osteoblasts. Toxic effects were not observed.
      The inhibition of the formation of osteoclasts was not reversed by the addition
      of farnesol and geranylgeraniol, excluding an effect of the monoterpenes through
      the mevalonate pathway. A high concentration of 1 mM was required to inhibit the
      activation of osteoclasts. This effect, shown for menthol and borneol, was
      reversible. CONCLUSIONS: The results suggest that the monoterpenes inhibit bone
      resorption in vivo through a direct effect on the formation of osteoclasts acting
      mainly on the hemopoietic cells.

PMID- 16598386
TI  - An update on the role of topical metronidazole in rosacea.
AB  - Topical metronidazole (Noritate 1% Cream, Dermik; MetroCream 0.75% Cream,
      MetroLotion 0.75% Lotion, Metrogel 0.75% and 1% Topical Gel, Galderma) has been
      used for the treatment of rosacea for over 30 years. Several placebo-controlled
      trials have demonstrated its effectiveness in the treatment of moderate-to-severe
      rosacea. It is also effective in preventing relapses of disease and is well
      tolerated by most patients. A growing number of formulations are available.

PMID- 16598384
TI  - BMP signaling is required for RUNX2-dependent induction of the osteoblast
      phenotype.
AB  - RUNX2 expression in mesenchymal cells induces osteoblast differentiation and bone
      formation. BMP blocking agents were used to show that RUNX2-dependent osteoblast
      differentiation and transactivation activity both require BMP signaling and,
      further, that RUNX2 enhances the responsiveness of cells to BMPs. INTRODUCTION:
      BMPs and the RUNX2 transcription factor are both able to stimulate osteoblast
      differentiation and bone formation. BMPs function by activating SMAD proteins and
      other signal transduction pathways to stimulate expression of many target genes
      including RUNX2. In contrast, RUNX2 induces osteoblast-specific gene expression
      by directly binding to enhancer regions in target genes. In this study, we
      examine the interdependence of these two factors in controlling osteoblast
      differentiation in mesenchymal progenitor cells. MATERIALS AND METHODS: C3H10T1/2
      mesenchymal cells and primary cultures of marrow stromal cells were transduced
      with a RUNX2 adenovirus and treated with BMP blocking antibodies or the natural
      antagonist, NOGGIN. Osteoblast differentiation was determined by assaying
      alkaline phosphatase and measuring osteoblast-related mRNA using quantitative
      RT/PCR. Activation of BMP-responsive signal transduction pathways (SMAD,
      extracellular signal-regulated kinase [ERK], p38, and c-jun-N-terminal kinase
      [JNK]) was assessed on Western blots. RESULTS AND CONCLUSIONS: C3H10T1/2 cells
      constitutively synthesize BMP2 and 4 mRNA and protein, and this BMP activity is
      sufficient to activate basal levels of SMAD phosphorylation. Inhibition of BMP
      signaling was shown to disrupt the ability of RUNX2 to stimulate osteoblast
      differentiation and transactivate an osteocalcin gene promoter-luciferase
      reporter in C3H10T1/2 cells. BMP blocking antibodies also inhibited RUNX2
      dependent osteoblast differentiation in primary cultures of murine marrow stromal
      cells. Conversely, RUNX2 expression synergistically stimulated BMP2 signaling in
      C3H10T1/2 cells. However, RUNX2 did not increase the ability of this BMP to
      activate SMAD, ERK, p38, and JNK pathways. This study shows that autocrine BMP
      production is necessary for the RUNX2 transcription factor to be active and that
      BMPs and RUNX2 cooperatively interact to stimulate osteoblast gene expression.

PMID- 16598387
TI  - The forehead flap for nasal reconstruction: how we do it.
AB  - The forehead flap is a useful technique to reconstruct deep and large nasal
      defects. It can safely be performed under local anesthesia in an outpatient
      setting. Advantages of this flap include the fact that it provides an excellent
      color and texture match to the missing nasal skin. Disadvantages include the fact
      that it is at least a two-stage procedure and that often patients require "touch
      up" surgeries to provide the best possible cosmetic outcome.

PMID- 16598388
TI  - Congenital pulmonary sling, aorto-pulmonary window and pulmonary vein obstruction
      as a diagnostic and therapeutic challenge in an infant with VACTERL association.
AB  - In a newborn with anal atresia and urethral valves an incomplete VACTERL
      association, was diagnosed and a colon anus praeter was placed. Sweating and
      heart murmur led to cardiac diagnostics. By 2D colour Doppler echocardiography a
      huge atrial septal defect and pulmonary venous stenoses were diagnosed.
      Additionally, a pulmonary sling combined with an aortopulmonary window (AoPAw)
      was suspected and later confirmed by angiography. Heart failure developed and
      closure of the AoPAw, transplantation of the left pulmonary artery and closure of
      the atrial septal defect was performed at the age of 4 weeks. But the patient did
      not improve. Pulmonary hypertension with suprasystemic pressure in the right
      ventricle originating from a stenosis of the new orifice of the left pulmonary
      artery and obstruction of the right pulmonary veins was diagnosed by
      echocardiography and confirmed by angiography. At the age of 8 months the orifice
      of the left pulmonary artery was enlarged by a patch, the obstruction of left
      sided pulmonary veins was opened, and the rightsided pulmonary veins were newly
      implanted into the left atrium. Finally the inter-atrial communication was closed
      by a patch plastic. Again, postoperatively the patient improved only slightly. At
      the age of 10 months trans-septal catheterisation was performed. Angiography
      revealed a successful balloon dilatation of the long obstruction of the right
      pulmonary veins. Later on, an absorbable magnesium stent was implanted into the
      right upper pulmonary vein and medication with an endothelin antagonist was
      started. Temporarily the patient improved significantly. Within 6 weeks, right
      ventricular systolic pressure was again suprasystemic due to extreme inflow
      obstruction of the right pulmonary vein diagnosed by echocardiography. Severe
      heart failure developed and at the age of 1 year the patient died.

PMID- 16598389
TI  - Transhepatic approach for catheter interventions in infants and children with
      congenital heart disease.
AB  - We report on our experience with transhepatic access for catheter interventions
      in six children (age range 2.5 months-9 years). Three had systemic venous
      anomalies, and one infant a femoral venous occlusion. In two further patients
      with bradyarrhythmia after a Fontan operation with an intraatrial Gore-Tex
      tunnel, transhepatic access was chosen to achieve a perpendicular orientation of
      the transseptal needle to the atrial baffle, allowing puncture of the Gore-Tex
      membrane. Two of the patients underwent ablation of an accessory pathway; in one
      an atrial septal defect was closed. A 2.5 month old baby after Norwood I
      operation, underwent balloon dilation of the pulmonary arteries. Two patients
      after prior Fontan surgery underwent DDDR pacemaker implantation. The size of the
      introducer sheath ranged from 4 F up to two 9 F introducers in the same vein for
      pacemaker insertion. At the end of the procedure, hemostasis was achieved by
      external compression. RESULTS: Transhepatic access could be established in all
      six patients (using a mirror image approach in children with left atrial
      isomerism) and the interventional procedures could be performed as planned. In
      one patient with implantation of a permanent pacemaker, a subcutaneous hematoma
      occurred, requiring blood transfusion. CONCLUSION: In selected pediatric
      patients, transhepatic access for catheter intervention can easily be achieved.

PMID- 16598390
TI  - Large femoral aneurysm as a late complication after vessel closure device
      application.
AB  - Four months after a diagnostic coronary angiography followed by application of a
      vascular closure device, a female patient presented with an acute femoral pulsing
      tumor with strong pain in the groin area. There was no prior trauma. Color duplex
      sonography showed a large pseudoaneurysm of the right femoral artery. In
      addition, signs of an old hematoma were documented. Due to the large tumor
      affecting the arterial perfusion of distal arteries, the pseudoaneurysm was
      treated immediately by thrombin injection. After this procedure, arterial
      perfusion in the tumor was not detectable anymore and local symptoms decreased
      rapidly. This is a rare case of late pseudoaneurysm after femoral artery
      puncture.

PMID- 16598391
TI  - Partial compression of the right atrium caused by a haematoma after coronary
      artery bypass angioplasty.

PMID- 16598392
TI  - Treatment of a large coronary saphenous bypass graft aneurysm by implantation of
      covered stents.

PMID- 16598394
TI  - Recurrent tako-tsubo-like left ventricular dysfunction (apical ballooning) in a
      patient with pheochromocytoma - a case report.
AB  - Primarily described in Japan, tako-tsubo-like left ventricular dysfunction is a
      phenomenon characterized by transient apical ballooning in the absence of
      significant coronary artery disease. The clinical presentation includes symptoms
      like chest pain, dyspnea, syncope, electrocardiographic changes and elevated
      myocardial markers, all compatible with the diagnosis of an acute coronary
      syndrome. The underlying mechanism is supposed to be a catecholamine excess
      caused by various triggers. We describe a patient with a recurrent tako-tsubo
      phenomenon, who at work-up proved to have a pheochromocytoma as the most likely
      underlying disease.

PMID- 16598393
TI  - Release pattern of N-terminal pro B-type natriuretic peptide (NT-proBNP) in acute
      coronary syndromes.
AB  - BACKGROUND: Recently it has been found that BNP and NT-proBNP provide independent
      prognostic information in patients with acute coronary syndromes (ACS). However,
      little data are available on the time course of NT-proBNP levels in relation to
      onset of symptoms. METHODS AND RESULTS: We included 765 patients (236 females,
      aged 64 +/- 11 years) with an ACS (STEMI 42%, NSTEMI 41%, UAP 17%), who were
      referred for coronary angiography. NT-proBNP was assessed on admission and the
      next day. NT-proBNP values were related to the time duration from onset of
      symptoms until blood drawing with lowest values within 3 h and highest values 24
      36 h after onset of symptoms (147 (64-436) pg/ml and 1099 (293-3795) pg/ml,
      respectively, p < 0.001). Highest values for NT-proBNP on admission were found in
      patients with NSTEMI compared to patients with STEMI and UAP (912 (310-2258)
      pg/ml) vs 262 (85-1282) pg/ml) vs 182 (74- 410) pg/ml; p < 0.001), but no
      difference was present between STEMI and NSTEMI the day after admission (1325
      (532-2974) pg/ ml vs 1169 (555-3413) pg/ml; p = 0.676). In contrast NT-proBNP
      values remained unchanged in UAP (182 (74-410) pg/ml) vs 171 (53-474) pg/ml).
      CONCLUSION: The time interval from onset of symptoms to first blood collection is
      an important determinant for NT-proBNP values on admission in patients with an
      ACS and needs to be considered in clinical practice.

PMID- 16598395
TI  - Increased cardiac mRNA expression of matrix metalloproteinase-1 (MMP-1) and its
      inhibitor (TIMP-1) in DCM patients.
AB  - Left ventricular dilation and myocardial remodeling are hallmarks of dilated
      cardiomyopathy (DCM). It is assumed that left ventricular dilation is caused by
      the disintegration of the collagenous network by increased collagenolytic
      activity of matrix metalloproteinases (MMPs) and their adequate tissue inhibitors
      (TIMPs). In this study the myocardial MMP-1 and TIMP-1 mRNA expressions were
      investigated by using real-time quantitative PCR analysis from right septal
      endomyocardial biopsies of patients with dilated cardiomyopathy (n = 46) and
      control subjects (n = 11). The volume density (Vv%) of collagen was measured
      morphometrically. Classification was done according to LV diameters [left
      ventricular enddiastolic diameter (LVEDD, cm) calculated to body surface area
      (BSA, m(2))] into three DCM groups: group I (LVEDD-BSA > 2.7-3.0 cm/m(2)), group
      II ( > 3.0-3.6 cm/m(2)), group III ( > 3.6 cm/m(2)), controls (< 2.7 cm/m(2)).
      Compared with controls, the MMP-1 expression in patients with DCM was
      significantly increased (119.2 +/- 45.2 vs. 1.3 +/- 0.4; p < 0.001) as was TIMP-1
      expression (9.6 +/- 1.2 vs. 1.3 +/- 0.4; p < 0.01). Moreover the MMP-1 and TIMP-1
      expression varied according to LV diameter: group I (MMP-1: 8.7 +/- 3.5; p =
      0.33; TIMP- 1: 4.5 +/- 1.2; p < 0.01); group II (MMP-1: 211.4 +/- 86.0; p <
      0.001; TIMP-1: 12.5 +/- 1.9 ; p < 0.001); group III (MMP-1: 38.8 +/- 22.6; p <
      0.01; TIMP-1: 8.1 +/- 1.7; p < 0.001). Compared with controls, the collagen level
      in DCMPt. was significantly increased: 5.0 +/- 0.6 vol% vs 1.2 +/- 0.2 vol% p <
      0.001 and correlates with LV diameter. This study reveals that the overexpression
      of MMP-1, which is associated with an increased ratio of MMP-1/TIMP-1 in DCM,
      indicates an activated collagenolytic system while replacement fibrosis is
      accumulating. The MMP-1 overexpression is mainly found in moderately dilated DCM
      hearts (group II) indicating the dynamic process of LV dilation and the
      importance of collagenases in the early phase of LV remodeling.

PMID- 16598396
TI  - Effect of transcoronary ablation of septal hypertrophy on clinical outcome in
      hypertrophic obstructive cardiomyopathy associated with atrial fibrillation.
AB  - BACKGROUND: Relatively few reports on the clinical impact of atrial fibrillation
      (AF) in hypertrophic obstructive cardiomyopathy (HOCM) are available. The aims of
      our study are to report the effect of transcoronary ablation of septal
      hypertrophy (TASH) on clinical outcome in HOCM associated with AF and to evaluate
      the influence of AF on symptoms and quality of life in HOCM. PATIENT AND METHODS:
      In 80 consecutive patients (38 f, mean age 56 +/- 17 years) with severely
      symptomatic HOCM referred for interventional treatment, we analyzed the
      prevalence of AF based on 240 Holter ECG recordings and patients' history,
      retrospectively. Symptoms, quality of life, number of hospital admissions and
      hemodynamic performance were obtained in all patients before and after TASH.
      Mortality was additionally investigated by letter and telephone contact. RESULTS:
      The overall prevalence of AF was 29%. Paroxysmal AF was detected in 17 pts
      (21.3%), persistent AF in 5 pts (6.3%). Only 1 pt (1.3%) suffered from permanent
      AF. Symptoms due to AF were present in 52.6% of the AF patients. Quality of life
      score was markedly improved after TASH (15.9 +/- 3.8 vs. 20.7 +/- 3.8, p < 0.001)
      with no difference between sinus rhythm and atrial fibrillation. However,
      hospital admissions were more frequent in the AF group (0.85 +/- 1.84 vs. 0.28 +/
      0.81, p = 0.03) in 32 +/- 13 months. AF patients suffered more often from
      syncope before TASH (30 +/- 70% vs. 10 +/- 30%, p = 0.008). Two patients with
      sinus rhythm at baseline died after 32 +/- 13 months from cardiovascular cause.
      CONCLUSIONS: Atrial fibrillation is the major cardiac arrhythmia in severe HOCM.
      The majority of AF patients demonstrate AF specific symptoms. The paroxysmal type
      of atrial fibrillation dominates by far. Both patients with and without atrial
      fibrillation showed similar quality of life with marked improvement after TASH.

PMID- 16598397
TI  - Transradial unprotected left main coronary stenting supported by percutaneous
      Impella Recover LP 2.5 assist device.
AB  - Percutaneous coronary intervention (PCI) has been increasingly applied to
      patients with severely depressed left ventricular function and complex coronary
      lesions. The availability of hemodynamic support devices offers a promising
      option to reduce PCI-related complications in high-risk procedures. We report the
      case of a 79-year-old man who suffered from unstable angina. The coronary
      angiogram revealed multivessel disease including a significant distal left main
      (LM) stenosis. Additionally, the patient had a history of chronic lymphatic
      leukemia with immune hemolysis. Therefore, the patient was considered to be at
      exceptionally high mortality risk in case of cardiac surgery. We decided to
      perform a percutaneous revascularization of the LM supported by the Impella
      Recover LP 2.5 assist device. This case report discusses the principles of
      indications, technique and complications of this new addition to interventional
      cardiology.

PMID- 16598398
TI  - Early and mid-term results of the Shelhigh stentless bioprosthesis in patients
      with active infective endocarditis.
AB  - AIMS: This study investigated the early and mid-term results following valve
      replacement with the new Shelhigh stentless bioprosthesis made entirely of
      biological material in patients with active infective endocarditis (AIE).
      MATERIAL AND METHODS: Between 02/2000 and 12/2004, 164 patients (n = 122 men,
      mean age 59, 18-85 years) received implantation of an AIE Shelhigh stentless
      bioprosthesis in the aortic, mitral, tricuspid or pulmonary position. A total of
      119 patients (72.6%) had native AIE and 45 (27.4%) prosthetic AIE. A large
      proportion of the patients reached the operating room in a condition of cardiac
      decompensation: 37 (22.6%) patients were intubated, 40 (24.4%) had protracted
      septic shock and 41 (25.0%) required intensive catecholamine treatment. Surgery
      was regarded as urgent in 94 patients (57.4%) and was performed as an emergency
      procedure in 70 (42.6%). The mean follow-up time is 1.5 +/- 0.11 years (range, 5
      months to 5.2 years). Echocardiographic follow-up examinations were performed
      early postoperatively and after 12 months. RESULTS: In terms of the operative
      indication, we found a highly significant difference in the survival rate between
      patients who were operated on urgently vs in an emergency. In patients who died
      within 30 days, the main cause of death was septic multiorgan failure (67.6%).
      Only three patients required reoperation due to reinfection of the Shelhigh
      bioprostheses; this represents a reinfection rate of 1.8% in relation to the
      whole cohort. The postoperative echocardiographic examinations showed the
      Shelhigh valves to have very good hemodynamics without relevant pressure
      gradients. CONCLUSION: Our experience in the use of Shelhigh bioprostheses in
      patients with native and prosthetic endocarditis show the early and mid-term
      results, in particular the low reinfection rate and the good hemodynamics, to be
      comparable with the results achieved using homografts. Since these prostheses are
      readily available and their implantation straightforward, they are increasingly
      being used in patients with endocarditis. These promising results need to
      verified in the long term.

PMID- 16598401
TI  - Morbidity of temporary loop ileostomy in patients with colorectal cancer.
AB  - PURPOSE: This study was designed to quantify the temporary loop ileostomy-related
      morbidity in patients with colorectal cancer and contrast the morbidity rates
      after ileostomy closure before, during, and after the start of adjuvant therapy.
      METHODS: Between 1997 and 2004, 120 patients with colorectal carcinoma underwent
      colorectal resection and creation of a temporary loop ileostomy to protect the
      low anastomosis. Stoma-related complications and perioperative morbidity after
      ileostomy closure were assessed retrospectively by reviewing the medical records.
      RESULTS: Sixteen of the 120 patients (13.3 percent) suffered stoma-related
      complications, requiring early ileostomy closure in three. After ileostomy
      closure, anastomotic leakage of the ileoileostomy occurred in 3 of the 120
      patients (2.5 percent), 2 of them died postoperatively (1.7 percent). The rate of
      minor complications (16.7 percent in all patients) was much higher in patients
      undergoing adjuvant chemotherapy or radiochemotherapy (25.5 percent) than in
      patients receiving no additional therapy (9.2 percent). In the former patients,
      there was a trend toward fewer complications when ileostomy closure was performed
      before (12.5 percent), rather than during (42.9 percent) or after (21.2 percent),
      the start of adjuvant therapy. CONCLUSIONS: The morbidity following closure of a
      temporary loop ileostomy in colorectal cancer patients is much higher in patients
      receiving adjuvant chemotherapy or radiochemotherapy. The morbidity, however,
      might possibly be lowered to the level of patients receiving no additional
      therapy if ileostomy closure is performed before the start of adjuvant therapy.

PMID- 16598399
TI  - Bland-White-Garland syndrome and atrial septal defect - rare association and
      diagnostic challenge.
AB  - We report on a 40-year-old woman referred for evaluation of a cardiac murmur and
      dyspnea on exertion. The electrocardiogram (ECG) showed incomplete right bundle
      branch block, and echocardiography revealed a large atrial septal defect (ASD,
      ostium secundum type) with dilated right-sided heart chambers. At cardiac
      catheterization, a large left-to-right shunt (78% of the pulmonary blood flow)
      was found, and surprisingly, the additional diagnosis of anomalous origin of the
      left coronary artery from pulmonary artery (ALCAPA) was established. After ASD
      closure and left coronary artery ligation with implantation of a vein graft to
      the left anterior descending artery, she had an uneventful 18-years follow-up. We
      discuss the interaction of the two associated conditions, and based on the herein
      reported unusual combination, we highlight typical features of non-invasive
      examinations including auscultation, ECG, and echocardiography in adult patients
      with ALCAPA.

PMID- 16598400
TI  - Rapid progressive eosinophilic cardiomyopathy in a patient with Churg-Strauss
      syndrome (CSS).
AB  - Churg-Strauss syndrome (CSS) is a rare necrotizing, systemic vasculitis that is
      almost invariably associated with bronchial asthma. Although overall prognosis is
      good and treatment with corticosteroids alone or in combination with other
      immunosuppressive agents is typically successful, there are reports of patients
      that do not show signs of clinical improvement under the usual pharmacotherapy.
      Small clinical studies suggested that cardiac or gastrointestinal involvement is
      associated with an adverse prognosis. We here report the case of a 38 year old
      male patient with a history of bronchial asthma who was admitted to our hospital
      for further evaluation of progressive dyspnea. Blood eosinophilia, infiltrates of
      both lungs, signs of necrosis and eosinophil deposits on myocardial biopsy
      combined with a history of bronchial asthma established the diagnosis of CSS with
      cardiac involvement. We initiated an immunosuppressive therapy with prednisone
      and methotrexate. Upon tapering of the dosage of prednisone, we noticed worsening
      of symptoms and further deterioration of cardiac function. Despite the addition
      of cyclophosphamide and adjustment of heart failure medication, we were not able
      to stabilize the cardiac situation. Due to rapid progressive eosinophilic
      cardiomyopathy associated with CSS refractory to medical therapy, our patient was
      placed on the urgent heart transplantation waiting list and, in the meantime, has
      undergone successful cardiac transplantation.

PMID- 16598402
TI  - Laparoscopic colon resection for polyps: a good novice case?
AB  - PURPOSE: Laparoscopic colon resection of the endoscopically unresectable polyp
      has been considered an ideal case for the surgeon with moderate laparoscopic
      colectomy experience because tissues are not inflamed and the lymphadenectomy may
      not need to be as extensive compared with that required for cancer. To assess the
      appropriateness of this approach, we evaluated the incidence of invasive cancer
      in a series of laparoscopic colon resections for polyps. METHODS: A retrospective
      review was performed of 55 consecutive patients undergoing laparoscopic colon
      resection for endoscopically unresectable polyps during a 35-month period.
      Colonoscopy data, polyp characteristics, and final colon pathology were reviewed.
      RESULTS: On final pathologic examination, 18.2 percent of patients had invasive
      adenocarcinoma. Patient age, gender, indication for colonoscopy, polyp size,
      polyp location, polyp characteristics, and colonoscopic biopsy pathology were not
      predictive of adenocarcinoma on final pathology. CONCLUSIONS: A significant
      number of endoscopically unresectable polyps harbor adenocarcinoma, thereby
      requiring a formal lymphadenectomy at resection. Caution should be exercised when
      considering the laparoscopic resection of an endoscopically unresectable polyp as
      a "learning" case.

PMID- 16598403
TI  - The utility of pudendal nerve terminal motor latencies in idiopathic
      incontinence.
AB  - PURPOSE: Pudendal nerve terminal motor latency testing has been used to test for
      pudendal neuropathy, but its value remains controversial. We sought to clarify
      the relationship of pudendal nerve terminal motor latency to sphincter pressure
      and level of continence in a cohort of patients with intact anal sphincters and
      normal pelvic floor anatomy. METHODS: We reviewed 1,404 consecutive patients who
      were evaluated at our pelvic floor laboratory for fecal incontinence. From this
      group, 83 patients had intact anal sphincters on ultrasound and did not have
      internal or external rectal prolapse during defecography. These patients were
      evaluated by pudendal nerve terminal motor latency testing, a standardized
      questionnaire, and anorectal manometry, which measured resting and squeeze anal
      pressures. Incontinence scores were calculated by using the American Medical
      Systems Fecal Incontinence Score. Values were compared by using the Fisher's
      exact test and Wilcoxon's rank-sum test; and significance was assigned at the P <
      0.05 level. RESULTS: 1) Using a 2.2-ms threshold, 28 percent of patients had
      prolonged pudendal nerve terminal motor latency unilaterally and 12 percent
      bilaterally. 2) At a 2.4-ms threshold, 18 percent of patients had prolonged
      pudendal nerve terminal motor latency unilaterally and 8 percent bilaterally. 3)
      Bilaterally prolonged pudendal nerve terminal motor latency was significantly
      associated with decreased maximum mean resting pressure and increased Fecal
      Incontinence Score, but not decreased maximum mean squeeze pressure, at both 2.2
      ms and 2.4-ms thresholds. 4) Unilaterally prolonged pudendal nerve terminal motor
      latency was not associated with maximum mean resting pressure, maximum mean
      squeeze pressure, or fecal incontinence score at either threshold. CONCLUSIONS:
      The majority of incontinent patients with intact sphincters have normal pudendal
      nerve terminal motor latency. Bilaterally but not unilaterally prolonged pudendal
      nerve terminal motor latency is associated with poorer function and physiology in
      the incontinent patient with an intact sphincter.

PMID- 16598404
TI  - Results of lateral internal sphincterotomy for chronic anal fissure with
      particular reference to quality of life.
AB  - PURPOSE: The aim of this study was to investigate the effects of lateral internal
      sphincterotomy on quality of life in patients with chronic anal fissure using the
      Gastrointestinal Quality of Life Index and the Fecal Incontinence Quality of Life
      Scale. METHODS: Adult patients with chronic anal fissure underwent lateral
      internal sphincterotomy with the open technique. Two hundred forty-four patients
      completed the Gastrointestinal Quality of Life Index questionnaire at admission
      and at 12 months postoperatively. The Fecal Incontinence Severity Index score was
      calculated preoperatively and at 2 and 12 months postoperatively. The Fecal
      Incontinence Quality of Life Scale was administered to any patient who had a
      Fecal Incontinence Severity Index score greater than 0 at 12 months
      postoperatively. RESULTS: The mean preoperative Gastrointestinal Quality of Life
      Index score was 118.34 +/- 6.33, which developed to 140.74 +/- 2.38
      postoperatively (P< 0.001). At the two-month follow-up, 18 patients (7.38
      percent) had a Fecal Incontinence Severity Index score greater than 0. By 12
      months, the number of patients with Fecal Incontinence Severity Index score
      greater than 0 was reduced to seven (2.87 percent). These seven patients had a
      Gastrointestinal Quality of Life Index score similar to that of the group with
      postoperative Fecal Incontinence Severity Index score of 0, and only three
      patients (1.22 percent) had evident deterioration in the Fecal Incontinence
      Quality of Life Scale. The 12-month total Gastrointestinal Quality of Life Index
      score of the three patients who developed anal abscess/fistula after
      sphincterotomy (139.33 +/- 3.21) was similar to the Gastrointestinal Quality of
      Life Index score of those without complications. However, the Gastrointestinal
      Quality of Life Index score of the recurrent cases (111.53 +/- 3.53) was
      apparently low. CONCLUSION: The gastrointestinal quality of life improved
      significantly following lateral internal sphincterotomy, regardless of the
      surgical complications or postoperative disturbances of continence. Only 1.2
      percent of the patients experienced deterioration in Fecal Incontinence Quality
      of Life Scale.

PMID- 16598405
TI  - Evaluation of the risk of a nonrestorative resection for the treatment of
      diverticular disease: the Cleveland Clinic diverticular disease propensity score.
AB  - PURPOSE: The choice of operation for diverticular disease is a contentious issue,
      particularly in patients with acute symptoms. This study compares early outcomes
      between primary resection and anastomosis and Hartmann's resection and describes
      a propensity score for the selection of patients for nonrestorative procedures.
      METHODS: Data were collected from 731 patients undergoing primary resection and
      anastomosis (Group 1) and 123 patients undergoing primary Hartmann's resection
      (Group 2) for diverticular disease in a single tertiary referral center from
      January 1981 to May 2003. Multifactorial logistic regression was used to develop
      a propensity score for estimating the likelihood of performing a nonrestorative
      procedure. RESULTS: Operative 30-day mortality and surgical or medical
      complications were 0.7 percent, 26.0 percent, and 4.8 percent for primary
      resection and anastomosis and 12 percent, 43.9 percent, and 14.6 percent for
      Hartmann's resection, respectively (P < 0.001). There was no difference in the
      readmission rates between primary resection and anastomosis and Hartmann's
      resection (7.6 percent vs. 9.9 percent, P = 0.428). Laparoscopy was used for 32.7
      percent of primary resection and anastomosis vs. 1.6 percent for Hartmann's
      resection (P < 0.001). Independent predictors in favor for Hartmann's resection
      were body mass index > or = 30 kg/m2 (odd's ratio = 2.32), Mannheim peritonitis
      index >10 (odd's ratio = 6.75), operative urgency (emergency, urgent vs. elective
      surgery, odd's ratio = 16.08 vs. 13.32), and Hinchey stage > II (odd's ratio =
      27.82). The area under the receiver operating characteristic curve for the choice
      of operative procedure was 93.9 percent. CONCLUSIONS: Although Hartmann's
      resection was associated with a higher incidence of postoperative adverse events,
      the choice of operation was dependent on the patient presentation and intra
      abdominal contamination, which can be quantified in the preoperative setting by
      the Cleveland Clinic diverticulitis propensity score.

PMID- 16598406
TI  - "Latch on to the affirmative: don't mess with Mr. In-Between".

PMID- 16598407
TI  - Selective cytotoxicity of recombinant STXA1-GM-CSF protein in hematopoetic cancer
      cells.
AB  - Chimeric proteins are composed of a cell-targeting moiety and a cell-killing
      moiety. In this study, a chimeric protein, STXA1-GM-CSF, composed of catalytic
      domain of Shiga toxin (A1) and granulocyte-macrophage colony-stimulating factor
      (GM-CSF) was constructed and expressed in E. coli. Cytotoxicity, receptor
      blocking, and neutralization experiments revealed that the chimeric protein
      induced cytotoxic effect on different cell lines. This effect was found to be
      specific, due to the presence of the killing moiety (A1), which exerts its effect
      through a specific GM-CSF-targeting domain, by binding to its receptor present on
      those cell lines. These initial investigations indicate that the chimeric protein
      was functional; further analyses are required for its application.

PMID- 16598408
TI  - Unsuccessful intraventricular pentosan polysulphate treatment of variant
      Creutzfeldt-Jakob disease.
AB  - Pentosan polysulphate, delivered by chronic intraventricular infusion, has been
      proposed as a potential therapy for human prion disease. The first treated
      patient is still alive several years after treatment started. Here we describe in
      detail a case of variant Creutzfeldt-Jakob disease in which this treatment was
      started at a relatively early stage but had no definite clinical benefit. The
      patient died from disease progression 16 months after diagnosis and 5 months
      after pentosan polysulphate treatment was commenced.

PMID- 16598409
TI  - Anton's syndrome due to a giant anterior fossa meningioma. The problem of routine
      use of advanced diagnostic imaging in psychiatric care.
AB  - We present a case of blindness and Anton's syndrome in a psychiatric patient with
      late diagnosis of a giant frontal meningioma. The criteria for advanced
      diagnostic imaging in the psychiatric population are discussed. We conclude that
      MR or CT scan is indicated in psychiatric in-patients who fail to improve with
      standard psychiatric treatment. This strategy should be submitted to a cost
      benefit analysis.

PMID- 16598410
TI  - A new simple therapeutic method for chronic subdural hematoma without irrigation
      and drainage.
AB  - BACKGROUND: We developed a new simple therapeutic method for the treatment of
      chronic subdural hematoma (CSDH) without irrigation and drainage. This method is
      characterized by replacement of the hematoma with oxygen. METHODS: Seventy
      patients (seventy-eight sides) with CSDH were treated with this method from May
      1994 to October 2002. For the complete replacement of the hematoma with oxygen,
      subdural tapping site was changed from the thickest area of the hematoma to the
      parietal tuber. Irrigation and drainage were not used in all patients. RESULTS:
      Neurological recovery after the treatment was satisfactory in all 70 patients. An
      average amount of replaced hematoma was 96.1 ml, ranging from 5 to 280 ml. An
      initial hematoma pressure ranged from 0 to 200 mm H2O (average: 92.1 mm H2O).
      During the follow up periods, clinical recurrence was noted in 7 patients (10%)
      and 7 sides (9.0%). CONCLUSION: The replacement of the hematoma with oxygen via
      percutaneous subdural tapping without irrigation and drainage is useful and less
      invasive method for the treatment of CSDH.

PMID- 16598411
TI  - MCTD: is it rare in India?
AB  - Mixed connective tissue disease (MCTD) has been rarely reported from India. Thus,
      we did a retrospective analysis of cases of MCTD seen at our hospital during the
      last 13 years. We found 16 cases among 441 patients with connective tissue
      disease. All the 16 patients (15 females) of MCTD fulfilled classification
      criteria by Kasukawa and at least one of the other two (Sharp's and Alarcon
      Sergovia). Raynaud's phenomenon, sclerodactyly, puffy fingers, esophageal
      hypomotility, and pulmonary disease were the most common manifestations. At a
      median follow-up of 12 months (1-172), 12 patients developed features of limited
      scleroderma and three patients had pulmonary hypertension.

PMID- 16598412
TI  - Catastrophic antiphospholipid syndrome in a 7-year-old girl.
AB  - Antiphospholipid syndrome (APS) has been recognized as the leading cause of
      vascular thrombosis in children. The syndrome may occur in isolation or in
      association with an underlying systemic disease, particularly systemic lupus
      erythematosus. Less than 1% of patients with APS present with a life-threatening
      condition resulting from thrombosis in multiple organs and subsequent multiorgan
      failure, which is defined as catastrophic APS. Early recognition of APS is
      essential because prompt and appropriate management can result in favorable
      outcome. We present the case of a 7-year-old girl with APS who presented with
      cerebral, femoral, and renal involvement in the second week of the disease
      progress. The patient presented with multiple thrombotic episodes and rapidly
      progressive renal failure. Renal cortical infarction was diagnosed by magnetic
      resonance imaging.

PMID- 16598413
TI  - Clinical manifestations and antiphosphatidylserine antibodies in patients with
      systemic lupus erythematosus: is there an association?
AB  - OBJECTIVE: Antiphospholipid antibodies are a group of heterogeneous
      autoantibodies which have been reported in systemic lupus erythematosus (SLE) and
      antiphospholipid syndrome (APS) in association with thrombosis, fetal loss, and
      thrombocytopenia. In this study, we aimed to reveal the prevalence and
      correlation of IgG, IgA, and IgM isotypes of antibodies to cardiolipin (aCL) and
      antiphosphatidylserine (aPS) with clinical and laboratory manifestations of SLE
      patients. METHODS: Fifty-nine SLE patients and 41 healthy controls were included.
      Fifteen of patients (25.4%) had secondary APS. aCL and aPS antibody assays were
      performed by enzyme-linked immunosorbent assay. RESULTS: All isotypes of aCL and
      aPS antibodies except IgG were higher in patients with or without APS than those
      in the healthy controls (p<0.001). The most significant associations were found
      among migraine and IgA aCL (p<0.001), livedo reticularis and both IgM aCL and IgM
      aPS (p<0.001), migraine and IgM aCL (p<0.01), pulmonary involvement and IgM aCL
      (p<0.01), migraine and IgA aPS (p<0.01), and both thrombosis and migraine with
      IgM aPS (p<0.01). CONCLUSION: A relatively high prevalence of aCL and aPS
      antibodies was found in our SLE patients. It seems that isotypes of IgM aCL, IgM
      aPS, IgA aCL, and IgA aPS antibodies are correlated well with migraine and IgM
      aPS with thrombosis in SLE patients with secondary APS. The assessment of both
      IgM and IgA isotypes of aPS and aCL antibodies may be helpful in predicting these
      manifestations.

PMID- 16598414
TI  - Validation of a simplified technique for using the POPQ pelvic organ prolapse
      classification system.
AB  - Our objective was to determine the inter-examiner agreement of a simplified
      pelvic organ prolapse quantification (POPQ) exam and to assess its correlation
      with the standard POPQ exam. This study consists of two parts; both were
      performed in a prospective, randomized, blinded fashion on women presenting with
      complaints attributed to pelvic organ support defects. The first study was done
      to determine the inter-examiner reliability of a simplified POPQ exam. The
      simplified POPQ exam is based on the POPQ with similar ordinal staging but with
      only four points measured instead of nine. Forty-eight women underwent exams by
      five different investigators. The order of exams was randomized and the examiners
      were blinded to the results of each other's findings. The results of these two
      exams were compared using weighted kappa statistics. The second part of the study
      was done to determine the inter-system agreement between the simplified vs
      standard POPQ exam. A group of 49 women were examined by four different
      investigators: one using the simplified and the other using standard POPQ exams.
      The order of the exams was randomized and the examiners were blinded to the
      results of each other's exam. Kendall's tau-b statistics were used to determine
      the inter-system agreement. For the inter-examiner reliability of the POPQ exam,
      the average age was 60+/-13 years. The weighted kappa statistics for the inter
      examiner reliability of the simplified prolapse classification system were 0.86
      for the overall stage, 0.89 and 0.86 for the anterior and posterior vaginal
      walls, respectively, 0.82 for the apex/cuff, and 0.72 for the cervix. All
      demonstrate significant agreement. For the inter-system association between the
      simplified POPQ and standard POPQ, the average age was 61+/-15 year. The
      Kendall's tau-b value for overall stage was 0.90, 0.83, and 0.87 for the anterior
      and posterior walls respectively, and 0.78 for the cuff/apex and 0.98 for the
      cervix. There is good inter-examiner agreement of a simplified POPQ
      classification system and it appears to have good inter-system association with
      the POPQ.

PMID- 16598415
TI  - Validation of the M.D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT).
AB  - BACKGROUND: Symptom occurrence has been shown to predict treatment course and
      survival in patients with solid tumors. Primary brain tumor (PBT) patients are
      unique in the occurrence of neurologic symptoms. Currently, no instrument exists
      that measures both neurologic and cancer-related symptoms. METHODS: Patients
      diagnosed with PBT participated in this study. Data was collected at one point in
      time and included demographic and clinical factors, and the M.D. Anderson Symptom
      Inventory-Brain Tumor Module (MDASI-BT). The study evaluated the reliability and
      validity of the MDASI-BT in primary brain tumor patients. RESULTS: Two hundred
      and one patients participated in this study. Mean symptom severity of items as
      well as cluster analysis was used to reduce the number of total items to 22 (13
      core, 9 brain tumor items). Regression analysis showed more than half (56%) of
      the variability in symptom severity was explained by brain module items. The
      MDASI-BT measures six underlying constructs including affective, cognitive, focal
      neurologic deficit, constitutional, generalized symptom, and a gastrointestinal
      related factor. The internal consistency (reliability) of the instrument was
      0.91. The MDASI-BT was sensitive to disease severity based on performance status
      (P<0.001), tumor recurrence (P<0.01), and mean symptom interference (P<0.001).
      CONCLUSIONS: The 22 item MDASI-BT demonstrated validity and reliability in
      patients with PBT. This instrument can be used to identify symptom occurrence
      throughout the disease trajectory and to evaluate interventions designed for
      symptom management.

PMID- 16598416
TI  - Treatment options in childhood pontine gliomas.
AB  - BACKGROUND: Pontine gliomas are the subgroup of brainstem gliomas with the worst
      prognosis. Controversial treatment approaches are discussed. PATIENTS AND
      METHODS: Data of children with pontine gliomas treated in different prospective
      multi-center studies who were registered in the HIT-GBM database were pooled and
      analyzed addressing prognostic factors and the relevance of intensive treatment
      using contingency tables, Kaplan-Meier curves and Cox regression analyses.
      RESULTS: From 1983 to 2001, 153 patients (74 males, 79 females, mean age: 8.1
      years) with pontine gliomas were registered. Twenty-one tumors were low-grade and
      60 were high-grade gliomas (72 undefined histology: 67 no surgery, 5 incomplete
      data). Sixteen tumors were partially resected, and 125 were irradiated. Ninety
      children received chemotherapy according to the "HIT-GBM" protocols ("Hirntumor
      Glioblastoma multiforme"). The one-year overall survival rate (1YOS) of all
      patients with pontine glioma was 39.9+/-4.3%. None of the surviving patients had
      an observation time longer than 3.9 years. Favorable prognostic factors seemed to
      be age younger than 4 years, low-grade histology and smaller tumor. All three
      major treatment modalities including resection, irradiation and chemotherapy had
      prognostic relevance in univariable analysis. Chemotherapy remained beneficial,
      even if the analysis was restricted to the subgroup of irradiated tumors (1YOS
      45.8+/-5.4% vs. 34.4+/-13.5%, P=0.030). CONCLUSION: Irradiation is an effective
      element for the treatment of pontine gliomas. Intensive chemotherapy seems to be
      important in achieving a better OS.

PMID- 16598417
TI  - Expression of Notch and Wnt pathway components and activation of Notch signaling
      in medulloblastomas from heterozygous patched mice.
AB  - Hedgehog (Hh), Notch, and Wingless (Wnt) signaling control normal development of
      the cerebellum, and dysregulation of these signaling pathways are associated with
      medulloblastoma (MB). As an initial step in the study of the role of interacting
      signaling pathways in MB pathogenesis, we demonstrate the expression of several
      components of the Notch and Wnt signaling pathways, and activation of Notch
      signaling in MB from Ptch +/- mice that have elevated Hh signaling. We also show
      a marked downregulation in the expression of Notch2, Jagged1, Hes1, mSfrp1, and
      mFrz7 in cerebella of developing mice with reduced Hh signaling, suggesting that
      Hh signaling regulates the expression of these genes. Together with recent
      published data, these findings indicate that Hh signaling might synergize
      simultaneously with Notch and Wnt signaling in MB development by controlling
      Notch and Wnt pathway ligand, receptor and/or target gene expression.

PMID- 16598418
TI  - Phosphorylation of cAMP response element binding protein (CREB) as a marker of
      hypoxia in pituitary adenoma.
AB  - Hypoxia appears to be causatively related to pituitary adenoma. Currently, no
      biomarkers are available for the postoperative assessment of hypoxia in patient
      samples. Since the cAMP response element binding protein (CREB) is phosphorylated
      under hypoxic conditions, we examined whether CREB phosphorylation levels may be
      exploited as a novel biomarker for hypoxia in pituitary adenoma tissues. HP-75
      human pituitary adenoma cells were incubated in 21% or 1% oxygen (normoxia and
      hypoxia, respectively), and Western blotting was employed to compare the levels
      of CREB and phosphorylated CREB (p-CREB). Our results show that p-CREB levels are
      significantly elevated under 1% oxygen, whereas the total CREB concentration
      remains unchanged. We further tested whether this phosphorylation is applicable
      as a marker of hypoxia in pituitary adenoma tissues removed by transsphenoidal
      surgery from 45 patients (32 females and 13 males, 22-78 years old). Fluorescence
      double immunohistochemistry data revealed that p-CREB in adenoma tissues is
      significantly elevated, and displays a positive correlation with Knosp grading
      (Spearman rank correlation; P = 0.0483, r = 0.3412), but no significant
      association with tumor subtype (Kruskal-Wallis analysis, CREB, P = 0.1072; p
      CREB, P = 0.1888; phosphorylation ratio, P = 0.4916). Our findings collectively
      suggest that CREB phosphorylation may be employed as an in situ marker for
      hypoxia. Moreover, hypoxia and/or phosphorylation of CREB are associated with the
      cell invasiveness of pituitary adenomas.

PMID- 16598419
TI  - Diffusion-weighted MR imaging abnormalities in pediatric patients with surgically
      treated intracranial mass lesions.
AB  - INTRODUCTION: Diffusion-weighted imaging (DWI) is a magnetic resonance imaging
      (MRI) technique that measures the degree of water diffusion in vivo. DWI
      abnormalities are frequently observed on immediate postoperative imaging
      following surgical resection of gliomas in adults. These abnormalities
      subsequently demonstrate contrast enhancement, which may be confused with lesion
      recurrence. The purpose of this study was to investigate the occurrence of these
      postoperative abnormalities in pediatric patients with intracranial mass lesions.
      METHODS: Thirty-three consecutive patients <or=18 years old with a newly
      diagnosed intracranial mass lesion underwent MRI, including DWI, before and
      immediately after surgical treatment. RESULTS: The median patient age was 9.9
      years (range 0.2-18 years). Supratentorial and infratentorial lesions were
      identified in 22 and 11 patients, respectively. Infiltrative and noninfiltrative,
      as well as benign and malignant lesions, were included. Postoperative imaging
      demonstrated areas of reduced diffusion adjacent to the resection cavity in 20
      (61%) cases. The median volume of these areas was 1.7 cm3 (range 0.3 cm3-12.0
      cm3). Subsequent imaging studies in 9 of the 18 cases showed contrast enhancement
      in the area corresponding to the DWI abnormality. There were no clinical deficits
      attributable to any of the diffusion abnormalities. There was no association
      between the occurrence of these abnormalities and whether the lesion was
      infiltrative, non-infiltrative, benign, or malignant. CONCLUSIONS: DWI
      abnormality on immediate postoperative MRI is common following surgery for newly
      diagnosed intracranial mass lesions in pediatric patients. Focal contrast
      enhancement in the postoperative period may be confused with recurrence for some
      lesions. Our study suggests that immediate postoperative DWI is useful in
      interpreting new areas of focal contrast enhancement on subsequent imaging in
      children who have had surgery for brain tumors.

PMID- 16598421
TI  - Disseminated pilocytic astrocytoma involving brain stem and diencephalon: a
      history of atypical eating disorder and diagnostic delay.
AB  - The association of weight loss and pediatric brain tumors that affect the
      diencephalon or brain stem with weight loss is a recognized, but not fully
      understood phenomenon. Tumors located in the hypothalamic region may induce the
      diencephalic syndrome (DS), which is characterized by profound emaciation with
      almost complete loss of subcutaneous fatty tissue. Tumors that compress or
      infiltrate the brain stem rarely cause both psychological disturbance and
      emaciation. The clinical presentation may be different, depending on the location
      of the lesion and age of the patient. In this report we present an unusual case
      of severe emaciation in a 4(9)/(12)-year-old girl with a juvenile pilocytic
      astrocytoma of the hypothalamic region and brain stem with neuroaxis
      dissemination. This case illustrates the importance of considering intracranial
      mass-lesions in the differential diagnosis of weight loss, psychological
      disturbance and atypical eating disorder. We discuss the importance of tumor
      multifocality and the role of patient age in the clinical presentation with
      reference to the literature.

PMID- 16598420
TI  - Inhibition of matrix degrading enzymes and invasion in human glioblastoma (U87MG)
      cells by isoflavones.
AB  - Glioblastoma multiforme is a primary brain tumor associated with extensive
      invasion into surrounding brain tissue. Matrix metalloproteinases (MMPs) and
      urokinase plasminogen activation (uPA) system are shown to be involved in tumor
      invasion as they help in degradation of extracellular matrix (ECM) proteins and
      thus assist in the movement of cells. MMP-2 and 9 were shown to be upregulated in
      gliomas, suggesting their involvement in invasion. Genistein and biochanin A are
      isoflavones commonly known as phytoestrogens and have some anticancer properties.
      We hypothesize that these two isoflavones can induce a lowering of tumor invasion
      by decreasing the activity of matrix degrading enzymes. In this study we
      investigated the effects of genistein and biochanin A on invasive activity of
      U87MG cells using the Calbiochem in vitro invasion assay system. Our results
      suggest that genistein and biochanin A induced a decrease in invasive activity of
      U87MG cells in a dose-related manner. Genistein also induced a decrease in EGF
      stimulated invasion thereby implicating an involvement of EGF-mediated signaling
      in invasion. Our results also show that treatment of U87MG cells with the two
      isoflavones induced decreases in the enzymatic activity of MMP-9 and the protein
      levels of MT1-MMP and uPAR.

PMID- 16598422
TI  - Atypical meningioma in Werner syndrome: a case report.
AB  - INTRODUCTION: Werner Syndrome, or adult progeria, is a rare autosomal recessive
      disorder caused by a mutation in the Werner Syndrome Gene belonging to the family
      of RecQ helicase. Malignant mesenchymal tumours and atherosclerosis are typical
      causes of death. Intracranial meningiomas are frequently described in these
      patients. CLINICAL PRESENTATION: We present the case of a 46-year-old man with
      Werner Syndrome and a convexity meningioma. The patient had a 2-year history of
      paresthesia and paresis in his right leg, which had worsened in recent months. He
      underwent surgery with Simpson grade II removal, with improvement of the slight
      paresis and no other neurological defects. The patient then underwent
      radiotherapy (60 Gy). Histological examination revealed an atypical meningioma.
      Cytogenetic analysis showed a hypodiploid clone with a complex karyotype
      characterized by monosomy 22 and deletion 1p. After 3 years' follow-up no
      relapses had occurred. CONCLUSION: 1p deletion correlates with meningioma
      progression and in this case correlates with histological examination. The
      chromosomal instability underlying Werner Syndrome could have fostered the
      complex karyotype.

PMID- 16598423
TI  - Glioma-produced extracellular matrix influences brain tumor tropism of human
      neural stem cells.
AB  - A major obstacle in the treatment of gliomas is the invasive capacity of the
      tumor cells. Previous studies have demonstrated the capability of neural stem
      cells (NSCs) to target these disseminated tumor cells and to serve as therapeutic
      delivery vehicles. Less is known about the factors involved in brain tumor
      tropism of NSCs and their interactions within the tumor environment. As gliomas
      progress and invade, an extensive modulation of the extracellular matrix (ECM)
      occurs. Tumor-ECM derived from six glioblastoma cell lines, ECM produced by
      normal human astrocytes and purified ECM compounds known to be upregulated in the
      glioma environment were analyzed for their effects on NSCs motility in vitro. We
      found that tumor-produced ECM was highly permissive for NSC migration. Laminin
      was the most permissive substrate for human NSC migration, and tenascin-C the
      strongest inducer of a directed human NSC migration (haptotaxis). A positive
      correlation between the degree of adhesion and migration of NSCs on different ECM
      compounds exists, as for glioma cells. Our in vitro data suggest that the ECM of
      malignant gliomas is a modulator of NSC migration. ECM proteins preferentially
      expressed in areas of glioma cell invasion may provide a permissive environment
      for NSC tropism to disseminated tumor cells.

PMID- 16598425
TI  - Giant invasive pituitary prolactinoma with falsely low serum prolactin: the
      significance of 'hook effect'.
AB  - The authors report a case of a patient with giant, invasive skull base tumor
      extending to the parasellar area discovered incidentally during the work-up for
      decreased memory. The patient's neurological exam was otherwise unremarkable.
      Endocrine evaluation performed at a local hospital showed a moderate
      hyperprolactinemia 103 ng/ml (normal up to 20 ng/ml). Given the large size of the
      tumor, the elevated prolactin (PRL) was interpreted to be secondary to stalk
      effect and patient underwent debulking surgery through a transcranial approach.
      Immunostaining of the excised tumor tissue was strongly positive for prolactin.
      His prolactin was found to be 13,144 ng/ml in our lab after surgery confirming
      the diagnosis of invasive giant prolactinoma. The patient developed a complete
      right third, fourth and sixth nerve palsy postoperatively. He was started on
      Cabergoline with normalization of his prolactin level and more than 50% decrease
      in residual tumor size over 9 months periods. There has been no clinically
      significant improvement in his right eye ophthalmoplegia since surgery. This case
      highlights the importance of 'Hook Effect' resulting in falsely low prolactin
      level, which may have significant therapeutic implication.

PMID- 16598424
TI  - Correlation of endoscopic biopsy with tumor marker status in primary intracranial
      germ cell tumors.
AB  - We retrospectively analyzed the results of eight patients who underwent
      endoscopic biopsy of a newly diagnosed primary intracranial germ cell tumor
      (GCT), and correlated tumor pathology with serum and cerebrospinal fluid (CSF)
      tumor markers and treatment outcome in order to determine the reliability of GCT
      sampling by this method. A biopsy diagnosis was made in each patient, and the
      tumor histology correlated with tumor marker measurements for all six patients
      diagnosed with germinoma and for one with a yolk sac tumor. One biopsy revealed
      only mature teratoma, an inconclusive result since the patient's serum and CSF
      tumor markers were elevated. No morbidity was experienced as a result of the
      operative procedure. Five of six patients diagnosed with germinoma responded
      completely to radiation therapy and are without evidence of disease, while one
      suffered a likely germinoma recurrence and was subsequently successfully
      retreated. We conclude that endoscopic biopsy of marker-negative germ cell tumors
      is a safe, reliable method of establishing a diagnosis of germinoma. However,
      endoscopic biopsy may fail to yield an accurate diagnosis in cases of malignant
      non-germinomatous tumor. We would thus conclude that when primary germ cell tumor
      is considered, endoscopic tumor biopsy is recommended in patients with a negative
      biochemical analysis, but not suggested for patients presenting with elevated
      tumor markers.

PMID- 16598427
TI  - Embryonal tumor with abundant neuropil and true rosettes. A new entity or only
      variations of a parent neoplasms (PNETs)? This is the dilemma.
AB  - A rare embryonal brain tumor has been diagnosed in a 4-year-old boy. The mass,
      located at the pons and mesencephalon, has been histologically classified as an
      embryonal tumor containing abundant neuropil and true rosettes. After surgical
      complete removal of the neoplasia, the child received intensive combined
      chemotherapy and radiotherapy. He is alive and free of disease at 34 months from
      surgery. Difficulties in histological definition, possible suggestions for
      treatment proposals are discussed.

PMID- 16598426
TI  - High-grade astrocytoma treated concomitantly with estramustine and radiotherapy.
AB  - Experimental and early clinical investigations have demonstrated encouraging
      results for estramustine in the treatment of malignant glioma. The present study
      is an open randomized clinical trial comparing estramustine phosphate (Estracyt)
      in addition to radiotherapy with radiotherapy alone as first line treatment of
      astrocytoma grade III and IV. The 140 patients included were in a good clinical
      condition with a median age of 55 years (range 22-87). Estramustine was given
      orally, 280 mg twice daily, as soon as the diagnosis was established, during and
      after the radiotherapy for a period of in total 3 months. Radiotherapy was
      delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due
      to misclassification, leaving 122 patients eligible for evaluation. Overall the
      treatment was well tolerated. Mild or moderate nausea was the most common side
      effect of estramustine. The minimum follow-up time was 5.2 years for the
      surviving patients. For astrocytoma grade III the median survival time was 10.6
      (1.3-92.7) months for the radiotherapy only group and 17.3 (0.4-96.9+) months for
      the estramustine + radiotherapy group. In grade IV the corresponding median
      survival time was 12.3 (2.1-89.2) and 10.3 (0.3-91.7+) months, respectively.
      Median time to progress for radiotherapy only and radiotherapy and estramustin
      group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV
      tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although
      there was a tendency for improved survival in grade III, no statistical
      significant differences were found between the treatment groups. No differences
      between the two treatment groups were evident with respect to quality of life
      according to the EORTC QLQ-protocol. In conclusion, this first randomized study
      did not demonstrate any significant improvement of using estramustine in addition
      to conventional radiotherapy, however, a trend for a positive response for the
      estramustine group was found in patients with grade III glioma.

PMID- 16598428
TI  - Intracranial tumors in adult population of the Varazdin County (Croatia) 1996
      2004: a population-based retrospective incidence study.
AB  - AIM: To estimate the incidence of intracranial tumors in the adult population of
      the Varazdin County, Croatia, for the 1996-2004 period. METHODS:  SETTING:
      Varazdin County General Hospital and four university hospitals in Zagreb, the
      capital of Croatia. STUDY PERIOD: January 1, 1996 to December 31, 2004. Incident
      patients: county residents admitted for newly diagnosed intracranial tumors
      according to the WHO diagnostic criteria. Demographic data were extracted from
      the 2001 Croatian census. Incidence rates (IRs) per 100,000 person-years (p-y)
      and annual IRs (per 100,000 persons) were determined and compared as incidence
      rate ratios (IRRs) with 95% CI. RESULTS: For primary intracranial tumors (PITs),
      IR was 12.1/100,000 p-y (95% CI: 10.3-14.2), comparable in men and women. The
      highest incidence was recorded for glioblastoma (IR 4.8, 3.7-6.2) and meningioma
      (IR 3.1, 2.2-4.2). The incidence of PIT was somewhat greater than that of
      metastatic tumors (IRR 1.58, 95% CI: 1.22-2.05, P < 0.001). Metastatic tumors
      were more frequent in men than in women, especially metastatic lung tumors (IRR
      6.08, 2.32-20.16, P < 0.001). IRs of all PIT taken together, neuroepithelial
      tumors cumulatively, nonepithelial tumors cumulatively, glioblastoma and
      meningioma were higher in the population aged > or = 40 vs. population aged < or
      = 39 (all IRRs with 95% CI greater than 1, P < 0.05 or < 0.001), comparable in
      men and women. Women were somewhat older than men at the time of diagnosis of
      PIT: median difference -6 years (95.1% CI: -10 to -1, P < 0.05). Annual IRs for
      all these tumor categories showed increasing trends over the study period.
      CONCLUSION: Overall, there was an increasing trend in the incidence of primary
      intracranial tumors in the Varazdin County. Data did not allow estimation for
      most of the specific tumor types.

PMID- 16598429
TI  - Synergy of gene-mediated immunoprophylaxis and microbeam radiation therapy for
      advanced intracerebral rat 9L gliosarcomas.
AB  - PURPOSE: Microbeam radiation therapy (MRT), a novel experimental radiosurgery
      that largely spares the developing CNS and other normal tissues, is tolerated
      well by developing animals and palliates advanced 9LGS tumors. This report, to
      our knowledge, is the first demonstration that gene-mediated immunotherapy
      (GMIMPR) enhances the efficacy of MRT for advanced 9LGS tumors. METHODS: Seventy
      six male Fischer 344 rats were implanted ic with 10(4)9LGS cells on d0. By d14,
      the cells had generated approximately approximately 40 mm3 ic 9LGS tumours,
      experimental models for therapy of moderately aggressive human malignant
      astrocytomas. Each of the 14 untreated (control) rats died from a large (>100 mg)
      ic tumor before d29 (median, d21). On d14, the remaining 62 rats were given
      deliberately suboptimal microbeam radiation therapy (MRT) by a single lateral
      exposure of the tumor-bearing zone of the head to a 10.1 mm-wide, approximately
      approximately 11 mm-high array of 20-39 microm-wide, nearly parallel beams of
      synchrotron wiggler-generated radiation (mainly approximately 50-150 keV X-rays)
      that delivered 625 Gy peak skin doses at approximately approximately 211 microm
      ctc intervals in approximately approximately 300 ms either without additional
      treatments (MRT-only, 25 rats), with post-MRT GMIMPR (MRT+GMIMPR, 23 rats:
      multiple sc injections of irradiated (clonogenically-disabled) GM-CSF gene
      transfected 9LGS cells), or with post-MRT IMPR (MRT+IMPR, 14 rats: multiple sc
      injections of irradiated (clonogenically-disabled) 9LGS cells. RESULTS: The
      median post-implantation survivals of rats in the MRT-only, MRT+GMIMPR and
      MRT+IMPR groups were over twice that of controls; further, approximately
      approximately 20% of rats in MRT-only and MRT+IMPR groups survived >1 yr with no
      obvious disabilities. Moreover, over 40% of MRT+GMIMPR rats survived >1 yr with
      no obvious disabilities, a significant (P<0.04) increase over the MRT-only and
      MRT+IMPR groups. SIGNIFICANCE: These data suggest that the combination of
      MRT+GMIMPR might be better than MRT only for unifocal CNS tumors, particularly in
      infants and young children.

PMID- 16598431
TI  - A case of intra-dural malignant peripheral nerve sheath tumor in thoracic spine
      associated with neurofibromatosis type 1.
AB  - We present a 25-year-old male patient with neurofibromatosis type 1 (NF1).
      Thoracic intra-dural extra-medullary tumoral mass was excised gross-totally and
      the patient was referred to oncology unit. Histopathological diagnosis was
      malignant peripheral nerve sheath tumor (MPNST), a rare sarcoma with a dismal
      prognosis. Tumor recurred in its previous site with an adjacent apical mass in
      the left lung 7 weeks following initial surgery and repeat surgery was performed
      with complete removal of intra-dural tumor. We report the first patient with
      intra-dural MPNST localized proximal to conus medullaris; in upper thoracic
      spine. It must always be considered the possibility of a rare but a devastating
      tumor, MPNST beside schwannomas and neurofibromas in patients with NF1 when an
      intra-spinal mass is diagnosed.

PMID- 16598430
TI  - Extraneural metastatic medulloblastoma in an adult.
AB  - Medulloblastoma is a rare malignancy in adults, accounting for approximately 1%
      of all primary brain tumors. Extraneural metastases have been reported in 10-30%
      of cases and most commonly involve bone; rarely lymph nodes, visceral organs and
      bone marrow may be involved with disease. We report here our experience with a 26
      year-old woman with medulloblastoma treated with gross total resection followed
      by radiation therapy to her craniospinal axis. She subsequently developed
      widespread metastatic disease involving bone exclusive of the calvarium and spine
      for which multi-agent salvage chemotherapy was utilized with initial good
      clinical response. She later relapsed within the lymph nodes and soft tissues of
      the pelvis and eventually suffered a local recurrence within the posterior fossa.
      The treatment of medulloblastoma, particularly salvage therapy following disease
      recurrence, is reviewed.

PMID- 16598432
TI  - Multiple intracranial metastases from a malignant peripheral nerve sheath tumor
      of the extremities.

PMID- 16598434
TI  - The effect of coloured overlays on reading ability in children with autism.
AB  - Abnormalities of colour perception in children with autistic spectrum disorders
      have been widely reported anecdotally. However, there is little empirical data
      linking difficulties in colour perception with academic achievement. The Wilkins
      Rate of Reading Test was administered with and without Intuitive Coloured
      Overlays to 19 children with autistic spectrum disorders and to the same number
      of controls individually matched for age and intelligence. Findings showed that
      15 out of 19 (79%) children with autism showed an improvement of at least 5% in
      reading speed when using a coloured overlay. In contrast only 3 of 19 (16%)
      control group children showed such an improvement. The findings suggest that
      coloured overlays may provide a useful support for reading for children with
      autism.

PMID- 16598433
TI  - The efficacy of alginate encapsulated CHO-K1 single chain-TRAIL producer cells in
      the treatment of brain tumors.
AB  - OBJECT: Patients with astrocytic tumors in the central nervous system (CNS) have
      low survival rates despite surgery and radiotherapy. Innovative therapies and
      strategies must be developed to prolong survival of these patients. The alginate
      microencapsulation method, used to continuously release a certain cytotoxic agent
      in the vicinity of the tumor, is such a novel therapeutic strategy. The
      biological functionality of the apoptosis inducing scFv425:sTRAIL protein, which
      was released through the microencapsulation method, was studied in vitro.
      Analysis of the intracerebral biocompatibility of alginate capsules was performed
      by implantation of empty alginate capsules in the brain of mice. METHOD: Chinese
      Hamster Ovary cells (CHO-K1) were recombinantly engineered to produce the single
      chain anti-EGFR-sTRAIL protein (scFv425:sTRAIL). The CHO-K1 producer cells were
      encapsulated in an alginate capsule with a semi-permeable membrane through which
      the scFv425:sTRAIL protein could be released. RESULTS: In vitro studies show
      maintained biological functionality of the released scFv425:sTRAIL protein. There
      was no immunological tissue response detectable after intracerebral implantation
      of the alginate capsules in mice brains. CONCLUSION: Biological functionality of
      the produced scFv425:sTRAIL protein is maintained and intracerebral
      biocompatibility of the capsules is warranted. Alginate encapsulation of CHO-K1-
      scFv425:sTRAIL--producer cells and subsequently their intracerebral implantation
      is technically feasible. This study justifies further in vivo experiments.

PMID- 16598435
TI  - Familial autoimmune thyroid disease as a risk factor for regression in children
      with Autism Spectrum Disorder: a CPEA Study.
AB  - A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was
      conducted through the Collaborative Programs of Excellence in Autism (CPEA),
      sponsored by the National Institute of Child Health and Human Development, to
      compare the family history of autoimmune disorders in children with ASD with and
      without a history of regression. A history of regression was determined from the
      results of the Autism Diagnostic Interview-Revised (ADI-R). Family history of
      autoimmune disorders was obtained by telephone interview. Regression was
      significantly associated with a family history of autoimmune disorders (adjusted
      OR=1.89; 95% CI: 1.17, 3.10). The only specific autoimmune disorder found to be
      associated with regression was autoimmune thyroid disease (adjusted OR=2.09; 95%
      CI: 1.28, 3.41).

PMID- 16598439
TI  - Right atrial myxoma.

PMID- 16598436
TI  - Dose dependent inhibitory effect of dietary caraway on 1,2-dimethylhydrazine
      induced colonic aberrant crypt foci and bacterial enzyme activity in rats.
AB  - Colon cancer has become one of the major causes of cancer mortality. We
      determined the effect of caraway (Carum carvi L.) on the development of aberrant
      crypt foci (ACF) and modulation of fecal bacterial enzyme activities in 1,2
      dimethylhydrazine (DMH)-induced experimental rat colon carcinogenesis. Male
      Wistar albino rats were divided into six groups and all the animals were fed
      15.8% peanut oil making a total of 20% fat in the diet. Group 1 served as control
      and group 2 animals received 90 mg/kg body weight caraway p.o. daily for 15
      weeks. To induce ACF, DMH (20 mg/kg body weight) was injected subcutaneously once
      a week for the first four weeks (groups 3-6). In addition caraway was
      administered at the dose of 30, 60 and 90 mg/kg body weight everyday orally for
      the entire period of 15 weeks (groups 4-6). First, we analyzed ACF number
      (incidence), multiplicity and its distribution along the colon in all
      experimental groups at the end of 15 weeks. Subsequently, we also assayed the
      fecal bacterial enzyme activities. ACF formation and the fecal bacterial enzyme
      activities were found to be significantly high in DMH-alone treated group as
      compared to control group. Caraway supplementation at three different doses
      significantly suppressed ACF development, bacterial enzyme activities and
      modulated oxidative stress significantly as compared to the unsupplemented DMH
      treated group. Results of our present study indicate that dietary caraway
      markedly inhibited DMH-induced colon carcinogenesis and the optimal dose of 60
      mg/kg body weight was more effective than the other two doses.

PMID- 16598437
TI  - Antiangiogenic effect of 2-benzoyl-phenoxy acetamide in EAT cell is mediated by
      HIF-1alpha and down regulation of VEGF of in-vivo.
AB  - Benzophenones and its analogues are known for wide range of biological
      properties. Synthetic benzophenone analogue 2-benzoyl -phenoxy acetamide (BP-1)
      is proven to be potent antitumor and proapoptotic activity against EAT cells in
      vivo. In the present report, we studied the antiangiogenic effect of BP-1 in EAT
      cells induced angiogenesis. Treatment with BP-1 in-vivo was demonstrated by the
      down regulation of the secretion of VEGF from EAT cells and inhibition of blood
      vessels formation indicating the potential angioinhibitory effect of BP-1 in EAT
      cells. HIF-1alpha protein, a transcription factor known to be key a regulator in
      hypoxia-induced angiogenesis was also down regulated by BP-1. Our findings
      indicated that, HIF-1alpha nuclear sequestration is repressed by BP-1 through
      inhibition of nuclear translocation. We postulate that diminished HIF-1alpha
      nuclear presence and activity in BP-1 treated EAT cells could be responsible for
      decreased VEGF expression and antiangiogenic effects.

PMID- 16598440
TI  - Carotid-artery stenting in a high-risk patient population--single centre, single
      operator results.
AB  - AIMS: The aim of this study was to assess the outcome of carotid-artery stenting
      (CAS) in high-risk patients in routine clinical settings while excluding the
      impact of multiple operators and the learning curve of individual operators on
      the outcome, and to determine the impact of individual risk factors, including
      vascular multimorbidity, on the outcome. METHODS AND RESULTS: A total of 143
      consecutive patients, 100 (69.9%) males and 43 (30.1%) females, mean age 68.7+/-8
      years treated between February 1999 and May 2004 in the Heart Centre Coswig by a
      single operator for a symptomatic (n=37) and asymptomatic (n=106) on average
      greater than 70% (82.3+/-10.7%) or 80% (85.0+/-9.1%) NASCET carotid-artery
      stenosis, respectively, were studied. At least one NASCET exclusion criteria was
      present in 140 patients (97.9%), and vascular multimorbidity was present in 94
      (65.7%) patients. In 28 (19.6%) patients there was a complete occlusion of the
      contralateral internal carotid artery and in 12 (8.4%) patients the procedure was
      performed prior to emergency coronary bypass surgery. In all, 47 (32.9%)
      procedures were performed without and 96 (67.1%) were performed with
      thromboembolic protection. Technical success was achieved in all patients.
      Combined neurological complications, TIA, PRIND and stroke, occurred in 5 (3.5%)
      patients, of which 3 (2.1%) were PRIND and 2 (1.4%) were strokes. The
      neurological complications were more frequent and more severe in symptomatic
      patients compared to asymptomatic patients (PRIND 2.7% vs 1.9%; stroke 0% vs
      5.4%). In patients in whom thromboembolic protection was used, the rate of
      neurological complications was lower compared to those without protection (PRIND
      1.0% vs 4.3%; stroke 1.0% vs. 2.1%). There was no death related to the procedure.
      Neurological complications were more frequent and more severe in patients with
      vascular multimorbidity compared to those with an isolated carotid-artery
      stenosis (4.2% vs 2.0%). The rate of neurological complications was similar in
      type II diabetics and nondiabetics (2.9% vs 4.1%). In 4.2%, minor complications
      related to the arterial puncture site were observed (3.5% hematoma not requiring
      blood transfusion, 0.7% pseudoaneurysm). At follow-up after a minimum of 6
      months, 9 (6.3%) patients had died, the majority of whom had died of
      cardiovascular disease (3.5%). CONCLUSIONS: CAS can be performed with an
      acceptable risk in high-risk patients in routine clinical settings when it is
      performed by an experienced operator. The use of thromboembolic protection
      devices reduces the risk of neurological complications. Presence of vascular
      multimorbidity, but not diabetes, appears to increase the risk of all causes and
      of neurological complications.

PMID- 16598441
TI  - Normalization of coronary blood flow in the infarct-related artery after
      intracoronary progenitor cell therapy: intracoronary Doppler substudy of the
      TOPCARE-AMI trial.
AB  - BACKGROUND: Coronary microvascular dysfunction contributes to infarct extension
      and poor prognosis after an acute myocardial infarction (AMI). Recently,
      progenitor cell application has been demonstrated to improve neovascularization
      and myocardial function after experimental myocardial infarction. Therefore, we
      investigate coronary blood flow regulation in patients after AMI treated with
      intracoronary progenitor cell therapy. METHODS AND RESULTS: In the TOPCARE-AMI
      trial, patients received either bone marrow-derived or circulating progenitor
      cells into the infarct-related artery 3-7 days after AMI. The present substudy
      investigates in 40 patients coronary blood flow regulation at the time of
      progenitor cell therapy and at 4-month follow-up by i.c. Doppler in the infarct
      artery as well as a reference vessel. At the initial measurement, coronary flow
      reserve (CFR) was reduced in the infarct artery compared to the reference vessel
      (median 2.5 vs. 3.4, p<0.001). At 4-month follow-up, intracoronary progenitor
      cell therapy was associated with a normalization of CFR in the infarct artery
      (median 3.9 vs. reference vessel 3.8, p=0.15). CFR also improved in the reference
      vessel, but mechanisms were different: reference vessel increase in CFR was
      secondary to an increased basal vascular resistance, probably due to reduced need
      for hypercontractility. In contrast, in the infarct artery, adenosine-induced
      minimal vascular resistance profoundly decreased, indicating an increased maximal
      coronary vascular conductance capacity. In addition, in a non-randomized matched
      control group (n=8), minimal vascular resistance in the infarct artery was
      significantly elevated compared to progenitor cell treated patients 4 months
      after AMI (p=0.012). CONCLUSIONS: Intracoronary progenitor cell therapy after AMI
      is associated with complete restoration of coronary flow reserve due to a
      substantial improvement of maximal coronary vascular conductance capacity. The
      clinical importance of improved microcirculation by progenitor cell therapy in
      patients after AMI has to be established in further randomized trials.

PMID- 16598442
TI  - NT-pro-BNP in obstructive sleep apnea syndrome is decreased by nasal continuous
      positive airway pressure.
AB  - OBJECTIVE: The aim of this study was to evaluate the impact of obstructive sleep
      apnea syndrome (OSAS) on B-type natriuretic peptide (BNP) and to determine the
      effect of nasal continuous positive airway pressure (nCPAP) treatment on BNP
      levels. BACKGROUND: Increased sympathetic activity, repetitive rises in blood
      pressure, and apnea-induced wall stress may contribute as a trigger to release
      BNP in OSAS. However, there is uncertainty about whether OSAS affects BNP and
      whether application of nasal continuous positive airway pressure (nCPAP)
      ventilation affects release of BNP. PATIENTS AND METHODS: A prospective study in
      69 consecutive patients with suspected sleep disordered breathing referred to our
      sleep laboratory was conducted. OSAS was confirmed in 26 normotensive and 34
      hypertensive patients and ruled out in nine normotensive patients (controls) by
      polysomnography (PSG). RESULTS: Baseline N-terminal fragment of BNP prohormone
      (NT-pro-BNP) did not differ significantly between OSAS patients (hypertensive:
      mean +/-SEM 60.8+/-9.9 pg/ml, normotensive: 43.2+/-6.8 pg/ml) and controls
      (36.5+/-8.5 pg/ml). Application of CPAP resulted in a significant decrease of NT
      pro-BNP in hypertensive (60.8+/-9.9 pg/ml to 47.6+/-7.4 pg/ml, p=0.023) and
      normotensive OSAS (43.2+/-6.8 pg/ml to 29.6+/-5.3 pg/ml, p=0.0002). In contrast,
      controls showed no significant differences in NT-pro-BNP after a second PSG
      (36.5+/-8.5 pg/ml to 40.7+/-12.3 pg/ml, p=0.597). CONCLUSIONS: Normotensive and
      hypertensive OSAS was not associated with a significant elevation of NT-pro-BNP.
      Application of nCPAP decreased NT-pro-BNP levels significantly in normotensive
      and, in particular, hypertensive OSAS. These findings may provide further
      evidence of the potential for nCPAP to improve cardiovascular comorbidity and co
      mortality in OSAS and sleep disordered breathing, in general.

PMID- 16598444
TI  - Prolonged asystole provoked by head-up tilt testing.
AB  - We describe a patient with a history of neurocardiogenic syncopes who had a
      positive headup tilt test that resulted in an lasting asystole lasting 34
      seconds. However, the previously carried out Schellong test with a 30-min phase
      of standing showed a normal result. The patient showed typical orthostatic
      symptoms while tilted at the angle of 75 degrees. Shortly before asystole
      occurred, heart rate variability showed high frequency bands, indicating vagal
      stimulation. The pathophysiology of neurocardiogenic syncope (NCS) in context
      with heart rate variability is discussed. This patient was successfully treated
      with propranolol. This case shows the utility of a provocative head-up tilt test
      in establishing the diagnosis of NCS. If the Schellong test is normal, still
      further examination by tilt-table test is indispensable.

PMID- 16598443
TI  - Comparison of carvedilol and metoprolol in patients with acute myocardial
      infarction undergoing primary coronary intervention--the PASSAT Study.
AB  - BACKGROUND: The value of early therapy with beta-blocking agents in acute
      myocardial infarction (AMI) undergoing reperfusion is not yet well established.
      Newer beta-blocking agents such as carvedilol offer potential advantages in the
      setting of ischemia and reperfusion injury. METHODS: We randomized 100 patients
      with acute ST-elevation myocardial infarction (STEMI) to receive either 12.5 mg
      carvedilol or 50 mg metoprolol tartrate orally already before percutaneous
      coronary intervention (PCI) of the infarct-related artery, uptitrating to a daily
      target dose of 50 mg carvedilol or 150 mg metoprolol during the first week. Pts.
      were subjected to left ventricular (LV) angiography just before reperfusion and
      after 14 days to compare ejection fraction (EF) and regional wall motion
      abnormalities by quantitative LV analysis. Furthermore, kinetics of cardiac
      troponin T (cTnT), NT-proANP, NT-proBNP, endothelin, argenine vasopressin,
      epinephrine and norepinephrine were assessed during the first 12 hours and again
      at 2 weeks. In addition, reperfusion-induced rhythm abnormalities like VT,
      triplets, couplets, and bradycardic events were assessed continuously during the
      first 12 hours starting at reperfusion by Holter analysis. RESULTS: Both groups
      did not differ with respect to onset of pain, target vessel, extent of coronary
      heart disease, age, gender, rate of stenting or use of a GP IIb/IIIa inhibitor,
      pre- and postinterventional TIMI flow grade, time course of heart rate or blood
      pressure. There were neither significant differences in the cardiac and
      neurohumoral markers nor in the occurrence of arrhythmias between both treatment
      groups. Within 14 days, EF improved by 5.8+/-2.0% (mean+/-SEM) in the metoprolol
      group and by 5.2+/-2.1% in the carvedilol group (n.s.). Area of infarction was
      reduced by 6.1+/-2.9% in the metoprolol group and by 12.8+/-3.6% of total LV
      outline in the carvedilol group (n.s.). Maximum hypokinesia in the central
      infarcted region was diminished by 0.40+/-0.11 standard deviation (SD) in the
      metoprolol group and by 0.34+/-0.13 SD in the carvedilol group (n.s.).
      CONCLUSION: In the setting of direct PCI in acute STEMI, administration of
      carvedilol before reperfusion appears not to be superior to metoprolol with
      respect to myocardial injury and improvement of global and regional LV function.
      The study documents equivalent improvement of LV function and similar kinetics of
      cardiac and neurohumoral markers in pts. with acute STEMI undergoing direct PCI
      if the pts. were immediately treated with either carvedilol or metoprolol. Thus,
      superiority of carvedilol in experimental studies did not translate into a
      clinical benefit.

PMID- 16598445
TI  - The coronary-subclavian-vertebral steal syndrome (CSVSS).
AB  - OBJECTIVE: Reverse flow in the internal thoracic artery (ITA) after coronary
      bypass surgery due to an occlusion or severe stenosis of the subclavian artery is
      a rare situation. Symptoms can be recurrent and intermittent angina pectoris in
      the case of a coronary-subclavian steal (CSSS) or-in addition with cerebral
      symptoms-in the case of a coronary-subclavian-vertebral steal syndrome (CSVSS).
      METHOD: We describe the cases of four patients with recurrent angina pectoris 5,
      11, and 14 years as well as directly after coronary bypass surgery with LITA
      grafts to LAD. In two patients there was the additional aspect of vertebral steal
      symptoms with dizziness and intermittent drop attacks. RESULTS: A PTA of the
      subclavian occlusions in three cases was not feasible, so that three patients
      were operated on by extrathoracal approach and carotido-subclavian bypass (CSB)
      in two cases, and local thrombendarteriectomy of the subclavian and vertebral
      artery (TEA)+ -patchplasty in one case. Patient 4 was treated by PTA and stent
      placement into the subclavian artery. Antegrade flow in all four LITAs could be
      achieved resulting in immediate relief from angina pectoris and cerebral
      symptoms. Patients 1 and 3 showed no further symptoms with equal BP of the upper
      extremities and anterograde flow in the LITA grafts and vertebral artery at 10
      month follow-up. Patient 2 unfortunately died from an unrelated cause (asthmatic
      state) 4 months after the operation despite an uneventful recovery. CONCLUSION:
      The occurrence of a CSSS or CSVSS after coronary bypass surgery with retrograde
      flow in the ITA graft (as described in our four patients) is a rare, but
      potentially hazardous, situation. If the subclavian occlusion is not amenable to
      endovascular strategies, the extrathoracal approach by CSB or local TEA and
      patchplasty provides an excellent means with good midterm and long-term results.

PMID- 16598446
TI  - Cardiovascular dysphagia.
AB  - A 72-year-old patient was admitted to our clinic following posterior wall
      myocardial infarction. Furthermore, he had suffered from dysphagia and
      intermittent regurgitation for a time period of two months. Radiological
      diagnostics revealed an esophageal impingement by the left atrium and the
      descending aorta due to severe thoracic scoliosis. This represents an infrequent
      form of cardiovascular esophageal compression.

PMID- 16598447
TI  - [Statement of the Working Group of the Germany Society on the safety of
      asynchronous ventricular pacemaker stimulation ].

PMID- 16598448
TI  - Importance of Trp59 and Trp60 in chitin-binding, hydrolytic, and antifungal
      activities of Streptomyces griseus chitinase C.
AB  - The chitin-binding domain of Streptomyces griseus chitinase C (ChBD(ChiC))
      belongs to CBM family 5. Only two exposed aromatic residues, W59 and W60, were
      observed in ChBD(ChiC), in contrast to three such residues on CBD(Cel5) in the
      same CBM family. To study importance of these residues in binding activity and
      other functions of ChBD(ChiC), site-directed mutagenesis was carried out. Single
      (W59A and W60A) and double (W59A/W60A) mutations abolished the binding activity
      of ChiC to colloidal chitin and decreased the hydrolytic activity toward not only
      colloidal chitin but also a soluble high Mr substrate, glycol chitin. Interaction
      of ChBD(ChiC) with oligosaccharide was eliminated by these mutations. The
      hydrolytic activity toward oligosaccharide was increased by deletion of ChBD but
      not affected by these mutations, indicating that ChBD interferes with
      oligosaccharide hydrolysis but not through its binding activity. The antifungal
      activity was drastically decreased by all mutations and significant difference
      was observed between single and double mutants. Taken together with the
      structural information, these results suggest that ChBD(ChiC) binds to chitin via
      a mechanism significantly different from CBD(Cel5), where two aromatic residues
      play major role, and contributes to various functions of ChiC. Sequence
      comparison indicated that ChBD(ChiC)-type CBMs are dominant in CBM family 5.

PMID- 16598449
TI  - Retrovirus producer cell line metabolism: implications on viral productivity.
AB  - The production of retroviral vectors by human cell lines is still hampered by low
      titers making it relatively difficult to produce very large quantities of this
      vector of high interest for clinical gene therapy applications. Thus, to improve
      vector production, we studied the influence of different sugars alone or
      combinations of sugars on cell growth, vector titers, and metabolism of the
      producer cell. The use of fructose at 140 mM or a mixed medium (with glucose at
      25 mM and fructose at 140 mM) improved the virus titer three- to fourfold,
      respectively, and the producer cell productivity by fivefold. The increase in the
      cell productivity was due to a 1.5-fold increase in the vector stability, the
      remaining increase being due to higher cell specific productivity. The increase
      in the productivity was associated with lower glucose oxidation and an increase
      in the lactate and alanine yield. In the mixed medium, an increase in fatty acids
      derived from the glucose was observed in parallel with a reduction of glutamate
      and glutamine synthesis via the tricarboxylic acid (TCA) cycle acetyl-CoA and
      alpha-ketoglutarate, respectively. Although the higher productivities were
      associated with severe changes in the glycolysis, TCA cycle, and glutaminolysis,
      the cell energetic status monitored by phosphocreatine and adenosine triphosphate
      levels was not significantly affected. The synthesis of fatty acids and
      phospholipids were enhanced in the fructose or mixed media and are possibly key
      parameters in retroviral vector production.

PMID- 16598450
TI  - [Klippel-Trenaunay syndrome. A rare cause of recurrent macrohematuria: case
      report].
AB  - A 37-year-old man with Klippel-Trenaunay syndrome presented with an episode of
      painless severe gross hematuria. Magnetic resonance imaging (MRI) revealed
      vessels of significant diameter in the bladder wall. Diagnostic imaging is
      mandatory in order to be aware of the extent of the lesion as the bleeding
      identified intraoperatively may only be the "tip of the iceberg." If conservative
      means fail, laser coagulation should be the treatment of choice.

PMID- 16598451
TI  - Diabetic encephalopathy: A concept in need of a definition.

PMID- 16598452
TI  - Characteristics of peripheral arterial disease in Japanese type 2 diabetic
      patients.

PMID- 16598453
TI  - Contributions of prolonged contingent and noncontingent cocaine exposure to
      enhanced reinstatement of cocaine seeking in rats.
AB  - RATIONALE: Recent evidence suggests that prolonged cocaine self-administration
      produces escalation in drug-seeking behavior in rats analogous to the increased
      intake patterns observed in cocaine-dependent individuals. However, the
      contributions of prolonged access to cocaine taking vs the pharmacologic effects
      of the consequent increased cocaine exposure on escalation of drug-seeking
      behaviors have not been investigated. OBJECTIVE: The present study assessed the
      effects of these two factors on maintenance of cocaine self-administration and
      reinstatement of cocaine seeking. METHODS: Male, Sprague-Dawley rats were trained
      to self-administer cocaine (0.2 mg/i.v. infusion; FR1) for 1 h per day for 10
      sessions followed by short access (1 h/day), contingent long access (6 h/day), or
      noncontingent long access (1 h contingent + 5 h of yoked cocaine infusions/day;
      i.e., short access + yoked) to cocaine for 14 daily sessions. All rats underwent
      extinction training and were subsequently tested for the ability of cocaine
      paired cues or a cocaine-priming injection (7.5 mg/kg i.p.) to reinstate
      extinguished cocaine seeking. RESULTS: Rats in all groups maintained stable
      responding for cocaine reinforcement and subsequently showed significant
      reinstatement of cocaine-seeking behavior. Conditioned-cued reinstatement was
      enhanced after the contingent long access and short access + yoked cocaine
      exposure relative to short access cocaine exposure. Conversely, cocaine-primed
      reinstatement was enhanced after contingent long-access cocaine exposure relative
      to the other two conditions. CONCLUSIONS: Enhanced drug seeking produced by
      prolonged daily cocaine self-administration is due to a combination of behavioral
      and pharmacological factors. Specifically, conditioned-cued reinstatement is
      enhanced by increased cocaine intake and cocaine-primed reinstatement is enhanced
      by increased cocaine taking.

PMID- 16598455
TI  - A sequential injection fluorometric procedure for the determination of procaine
      in human blood and pharmaceuticals.
AB  - An automated procedure for the assay of procaine hydrochloride in human blood and
      pharmaceuticals was developed using a sequential injection (SI) technique with
      fluorometric detection and fluorescamine as the fluorescence probe. A few
      microliters of fluorescamine and procaine hydrochloride solutions were used in
      the SI system leading to the formation of a derivative, which was then excited by
      a 400-nm LED and whose emitted fluorescence was monitored at a wavelength of 494
      nm. A linear calibration graph was obtained with 10-200 ng mL(-1) (procaine) by
      loading 10.0 microL of sample solution and 5.0 microL of fluorescamine solution
      (both 0.125 % m/v). A detection limit of 2.6 ng mL(-1), defined as 3 times the
      blank standard deviation (3sigma), was achieved along with a sampling frequency
      of 25 h(-1) and a precision of 2.1 % RSD at the 50.0 ng mL(-1) level. Procaine
      contents in injection solutions from various pharmaceutical manufactures were
      analyzed and reasonable agreement was achieved between the values obtained by
      using the present procedure and the documented spectrophotometry, and both were
      coincident with the nominal concentrations. In addition, the degradation of
      procaine in human blood was investigated. A fast degradation of procaine in human
      blood was observed for the first 30 min, while afterwards the degradation was
      retarded.

PMID- 16598454
TI  - Diminished nicotine withdrawal in adolescent rats: implications for vulnerability
      to addiction.
AB  - RATIONALE: Enhanced reinforcing effects of nicotine during adolescence appear to
      contribute to the rapid development of dependence in this age group. However, the
      contribution of nicotine withdrawal to dependence in adolescents is unclear.
      OBJECTIVE: We compared motivational and somatic signs of nicotine withdrawal in
      adolescent and adult rats. MATERIALS AND METHODS: In experiment 1, motivational
      signs of nicotine withdrawal were compared using intracranial self-stimulation
      procedures after administration of mecamylamine (1.5 mg/kg, i.p.) in adolescent
      and adult rats made dependent on nicotine (9 mg/kg/day). Somatic signs of
      withdrawal were compared in two experiments using various doses of nicotine
      (adolescent doses: 0, 1.6, 3.2, 4.7 mg/kg/day; adult doses: 0, 1, 2.1, 3.2
      mg/kg/day, expressed as nicotine base) to produce dependence and one dose of
      mecamylamine (1.5 mg/kg, i.p.) to precipitate withdrawal (experiment 2) and in a
      subsequent experiment, using various doses of mecamylamine (0, 0.75, 1.5, 3.0
      mg/kg, i.p.) to precipitate withdrawal and a dose of nicotine (adolescent dose:
      4.7 mg/kg/day; adult dose: 3.2 mg/kg/day) that produced equivalent nicotine blood
      levels in these age groups (experiment 3). RESULTS: Adolescents did not display
      the decreases in brain reward function observed in adults experiencing
      withdrawal, and displayed fewer somatic signs of nicotine withdrawal relative to
      adults regardless of the dosing procedure used. CONCLUSION: The negative effects
      of nicotine withdrawal are lower during adolescence relative to later periods of
      development. Both the enhanced rewarding effects and the diminished nicotine
      withdrawal likely contribute to the rapid development of nicotine use during
      adolescence.

PMID- 16598457
TI  - Charge-transfer reactions at liquid/liquid interfaces and their applications in
      bioassays.

PMID- 16598456
TI  - Rapid screening of dioxin-contaminated soil by accelerated solvent
      extraction/purification followed by immunochemical detection.
AB  - Since soils at industrial sites might be heavily contaminated with
      polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs), there is a need for large-scale soil pollution surveys and, thus, for
      cost-efficient, high-throughput dioxin analyses. However, trace analysis of
      dioxins in complex matrices requires exhaustive extraction, extensive cleanup,
      and very sensitive detection methods. Traditionally, this has involved the use of
      Soxhlet extraction and multistep column cleanup, followed by gas chromatography
      high-resolution mass spectrometry (GC/HRMS), but bioanalytical techniques may
      allow much more rapid, cost-effective screening. The study presented here
      explores the possibility of replacing the conventional method with a novel
      approach based on simultaneous accelerated solvent extraction (ASE) and
      purification, followed by an enzyme-linked immunosorbent assay (ELISA). Both the
      traditional and the novel cleanup and detection approaches were applied to
      contaminated soil samples, and the results were compared. ELISA and GC/HRMS
      results for Soxhlet-extracted samples were linearly correlated, although the
      ELISA method slightly underestimated the dioxin levels. To avoid an unacceptable
      rate of false-negative results, the use of a safety factor is recommended. It was
      also noted that the relative abundance of the PCDDs/PCDFs, evaluated by principal
      component analysis, had an impact on the ELISA performance. To minimize this
      effect, the results may be corrected for differences between the ELISA cross
      reactivities and the corresponding toxic equivalency factor values. Finally, the
      GC/HRMS and ELISA results obtained following the two sample preparation methods
      agreed well; and the ELISA and GC/HRMS results for ASE extracts were strongly
      correlated (correlation coefficient, 0.90). Hence, the ASE procedure combined
      with ELISA analysis appears to be an efficient approach for high-throughput
      screening of PCDD-/PCDF-contaminated soil samples.

PMID- 16598458
TI  - Isocratic separation of ginsenosides by high-performance liquid chromatography on
      a diol column at subambient temperatures.
AB  - An improved high-performance liquid chromatographic method for separation of a
      number of ginsenosides has been developed. The influence of temperature (from 0
      to 25 degrees C) on the retention and separation of the ginsenosides was studied
      by applying a binary mobile phase (acetonitrile/water, 82:18 v/v) and a diol
      column (LiChrospher 100 Diol). The column temperature is one of the more
      important parameters for the retention and separation of the components
      investigated. Selected thermodynamic parameters, including changes of enthalpy
      (deltaH degrees) and entropy (deltaS degrees), were estimated from linear van't
      Hoff plots, and possible retention mechanisms were discussed. Moreover, the best
      separation conditions were selected based on optimization criteria including
      maximum retention time (t(R max)), minimum resolution (R(s min)), and relative
      resolution product (r). Temperature regions close to 14 degrees C offered the
      highest selectivity and almost equal distribution of the ginsenosides peaks
      across the chromatogram. Under such isocratic conditions, excellent separation of
      chromatographic standards and selected ginseng samples was achieved in less than
      16 min.

PMID- 16598459
TI  - Terms and notations for laser-induced breakdown spectroscopy.

PMID- 16598460
TI  - Analytical challenge. Goldberg variations challenge.

PMID- 16598461
TI  - Transport across artificial membranes-an analytical perspective.
AB  - Biosensors that make use of transport processes across lipid membranes are very
      rare even though a stimulus, the binding of a single analyte molecule, can
      enhance the sensor response manifold if the analyte leads to the transport of
      more than one ion or molecule across the membrane. Prerequisite for a proper
      function of such membrane based biosensors is the formation of lipid bilayers
      attached to a support that allow for the insertion of membrane peptides and
      proteins in a functional manner. In this review, the current state of the art
      technologies to obtain lipid membranes on various supports are described. Solid
      supported membranes on transparent and electrically conducting surfaces, lipid
      bilayers on micromachined apertures and on porous materials are discussed. The
      focus lies on the applicability of such membranes for the investigation of
      transport phenomena across lipid bilayers facilitated by membrane embedded
      peptides, channel proteins and transporters. Carriers and channel forming
      peptides, which are easy to handle and rather robust, are used frequently to
      build up membrane based biosensors. However, channel forming proteins and
      transporters are more difficult to insert functionally and thus, there are yet
      only few examples that demonstrate the applicability of such systems as biosensor
      devices.

PMID- 16598462
TI  - Serous retinal detachment in a patient with aplastic anemia associated with
      parvovirus B19 infection.
AB  - BACKGROUND: We report a case of unilateral serous retinal detachment (RD)
      associated with parvovirus B19 infection. CASE REPORT: A 28-year-old woman had a
      clinical history of autoimmune hemolytic anemia and pure red cell aplasia
      associated with parvovirus B19 infection. She demonstrated focal serous RD
      without retinal exudates. A focal cataract and anterior vitreous cells were also
      observed. Fluorescein angiography (FA) revealed accumulation of subretinal fluid,
      but no vascular leakage. After vitrectomy, the retina was re-attached and visual
      acuity returned to 20/20. IgM antibody to parvovirus and viral DNA were detected
      by polymerase chain reaction in the vitreous fluid obtained at surgery.
      CONCLUSION: To our knowledge, this is the first reported case of the presence of
      anti-viral IgM and viral DNA in vitreous sample. Furthermore, the ocular findings
      in our patient are definitively different from previously reported cases of
      parvovirus-associated ocular disorders.

PMID- 16598464
TI  - Unilateral retinitis pigmentosa with amblyopia in the fellow eye.
AB  - PURPOSE: The purpose was to report a case of unilateral retinitis pigmentosa with
      amblyopia in the other eye. METHODS: Eight years ago, a 36-year-old woman
      complained of peripheral visual field loss in her left eye when she covered her
      right eye. Complete ophthalmological examinations including fundus photography
      and fluorescein angiography, full-field electroretinography, dark adaptation, and
      microperimetry were performed. RESULTS: Best-corrected visual acuity of the
      patient was 0.2 with +2.5 diopters in her right eye and 0.3 with +1.5 diopters in
      her left eye. Fundus examination did not reveal any abnormalities in the right
      eye, but narrow retinal vessels, optic disc pallor, and peripheral retinal
      pigment clumping was found in the left eye. The full-field electroretinography
      was normal in the right eye, but rod response, cone response, and combined
      response were non-recordable, and 30-Hz response was very small in the left eye.
      Dark adaptation thresholds were normal in the right eye, but were dramatically
      elevated in the left eye. Microperimetry was normal in the right eye, but the
      visual field was reduced to a 2x5 degrees central field in the left eye.
      CONCLUSION: Unilateral retinitis pigmentosa with amblyopia in the other eye is a
      rare condition. The patient presented here had a case of unilateral retinitis
      pigmentosa with the other eye with ametropic amblyopia. It is necessary to
      perform functional and morphological ophthalmological examinations to confirm the
      diagnosis.

PMID- 16598463
TI  - In vitro phagocytosis of collagens by immortalised human retinal Muller cells.
AB  - PURPOSE: This study is a first step to investigate phagocytosis of collagens by
      human retinal Muller cells, since Muller cells could be involved in remodelling
      of the vitreous and vitreoretinal interface in the human eye. METHODS: Muller
      cells in culture were exposed to 2.0 microm fluorescent latex beads coated with
      BSA and human types I, II, and IV collagen and to non-coated beads for 2, 12, 24,
      and 48 h. To influence phagocytosis, cytochalasin B and anti-integrin subunits
      (alpha1, alpha2, and beta1) were added to the cells. Phagocytosis was evaluated
      by flow cytometry, transmission electron microscopy (TEM) and confocal
      microscopy. RESULTS: Muller cells preferred to phagocytose beads coated with type
      II collagen compared with type IV collagen-, BSA- and non-coated beads.
      Phagocytosis of type I collagen-coated beads was intermediate. TEM and confocal
      microscopic evaluation confirmed phagocytosis of the beads. No significant
      differences were observed in phagocytosis of type II collagen-coated beads in the
      case of addition of cytochalasin B and anti-integrin subunits.
      Immunohistochemical analyses revealed that Muller cells were positive, under all
      tested circumstances, for vimentin and CRALBP. Less than 5% of the cells tested
      were GFAP positive. CONCLUSIONS: Our observations demonstrate that human Muller
      cells in culture prefer to phagocytose type II collagen. In contrast, the
      phagocytosis of type IV collagen is comparable with the control coatings. We
      speculate that the relatively limited collagen phagocytosis by Muller cells
      supports a possible role for Muller cells in the slow process of vitreoretinal
      remodelling in adult human eyes.

PMID- 16598465
TI  - In vivo confocal microscopy of pigmented conjunctival tumors.
AB  - PURPOSE: To analyze the appearance of conjunctival pigmented tumors as seen by in
      vivo confocal microscopy. METHODS: Twenty-eight pigmented conjunctival tumors
      including 6 nevi, 13 acquired melanoses, 7 conjunctival melanomas, and 2
      extrascleral growths of uveal melanomas were examined by in vivo confocal
      microscopy using the Heidelberg Retina Tomograph (HRTII)/Rostock Cornea Modul
      (RCM). Confocal images were analyzed using predefined criteria by an observer
      masked to final histological diagnosis and a preliminary diagnosis was
      established. After excision, histology and immunohistochemistry using antibodies
      against S-100, Melan-A, HMB-45, Ki-67, CD3, and CD68 were performed in all
      specimens and compared with in vivo confocal images of the same lesions. RESULTS:
      Confocal microscopy images confirmed typical histopathological features of
      conjunctival pigmented tumors. Nest or diffuse collections of medium-sized
      uniform hyper- or hyperreflective cells in the stroma and stromal cysts lined
      with a multilayered epithelium were visible in 100% of conjunctival nevi. Small
      dendritic cells were typically observed in 100% of primary acquired melanoses
      (PAM) without atypia and in 2 out of 6 nevi. Large networks of hyperreflective
      dendritic cells were present in 100% of PAM with atypia. Whereas images of PAM
      without atypia and secondary complexion-associated melanosis showed
      hyperreflective granules confined to the basal epithelium in 67% of lesions, PAM
      with atypia presented with hyperreflective granules and patches throughout the
      epithelium in all cases. Malignant melanomas of the conjunctiva and extrascleral
      growths of uveal melanomas demonstrated large hyperreflective cells with
      prominent nuclei and nucleoli. In vivo confocal microscopy showed a sensitivity
      of 89% and a specificity of 100% to establish the correct diagnosis of
      conjunctival melanoma compared with histology. CONCLUSIONS: High correlations
      were found between in vivo confocal microscopy using near-infrared laser light
      and histology in the diagnosis of pigmented conjunctival lesions. In vivo
      confocal microscopy seems to be a valuable new tool in the differential diagnosis
      and follow-up of pigmented conjunctival tumors. It does not replace histology,
      but may assist in performing guided biopsy in tumors suspected clinically and/or
      with in vivo microscopy. In addition, in vivo confocal microscopy may support the
      clinical diagnosis of extrascleral involvement in uveal melanoma.

PMID- 16598466
TI  - The antibody response in experimental ocular toxoplasmosis.
AB  - BACKGROUND: The dynamics of the humoral immune response in ocular toxoplasmosis
      (OT) are poorly understood. We therefore investigated this process in a rabbit
      model of the disease. MATERIALS AND METHODS: Of 24 infection-naive adult rabbits,
      12 were left untreated and 12 were systematically infected with 5,000 tachyzoites
      of the non-cystforming BK strain of Toxoplasma gondii. Three months later, all
      rabbits were inoculated transvitreally with 5,000 tachyzoites of Toxoplasma
      gondii. Paired samples of aqueous humor and serum were analyzed temporally for
      their total and specific IgG contents. RESULTS: In infection-naive rabbits with
      primary OT, specific IgG reached detectable levels in the inoculated eyes between
      5 and 15 days after inoculation. In infection-immunized rabbits with secondary
      OT, a significant increase in specific IgG was regularly detected after 5 days.
      The antibody ratio C was diagnostic (> or =3) from day 15 onward in primary OT
      and from day 21 onward in secondary OT. In the uninfected partner eyes, the
      antibody ratio C was found sporadically diagnostic from day 15 onward in primary
      OT, but at no time in secondary OT. Specific IgG persisted both locally and in
      the serum until the end of the monitoring period (100 days). CONCLUSION: Our
      findings relating to the rabbit model of OT reveal three features of clinical
      relevance: a diagnostic window precedes the establishment of a humoral immune
      response; specific antibodies persist long after the cessation of disease
      activity; and in primary OT, the antibody ratio C may also increase in the
      uninfected partner eye.

PMID- 16598467
TI  - Varied expression of functionally important genes of RPE and choroid in the
      macula and in the periphery of normal human eyes.
AB  - BACKGROUND: Topographic differences in RPE and choroid between macular and
      peripheral areas of the eye may predispose to morphologic and cell survival
      changes with aging. An understanding of the molecular events that distinguish RPE
      and choroid by their spatial location could give hints for the identification of
      survival factors and the development of new therapeutic approaches. To determine
      the mRNA expression of functionally important genes in RPE and choroid of
      morphologically normal human eyes, tissue patches were dissected from the macula
      and peripheral locations. METHODS: The mRNA levels of 29 genes with known
      functions or expression in the RPE/choroid were quantified in these sections by
      real time RT-PCR. Variations in the mRNA expression were determined due to
      differences in the mean normalized expression (MNE) between different peripheral
      locations, left and right eye of the same donor, and eyes of different donors.
      RESULTS: In the macula, the lysosomal enzyme cathepsin D (1.27E+00+/-1.54E-01)
      and the MERTK ligand Gas6 (1.08E+00+/-1.60E-01) had the highest MNE, whereas the
      apoptosis inducer Fas-Ligand (1.41E-04+/-6.46E-05) and the ROS internalization
      receptor CD36 (2.15E-04+/-1.11E-05) demonstrated the lowest expression.
      Interestingly, the PEDF expression (1.80E-01+/-4.56E-02) was 10 times higher than
      the VEGF expression (1.84E-02+/-2.46E-03) in the macular area. For most of the
      analyzed genes (52%, e.g. MERTK, integrin alphaV and beta5, RPE65, tyrosinase,
      VEGF) there was equal gene expression in the macula and in the periphery. For 31%
      of the genes (e.g. CD36, MAP1B) there was higher expression in the macula and for
      17% of the genes (e.g. 11-cis RDH, VEGF-R2, PEDF) there was higher expression in
      the periphery. CONCLUSIONS: Whereas most of the analyzed genes expressed in RPE
      and choroid had equal mRNA expression levels in the macula and the periphery with
      donor dependent variations, there are important exceptions in genes that are
      involved in the maintenance of a specific vascular status in the macula (PEDF,
      VEGF and VEGR-R2) and in the recycling of rod outer segments (11-cis RDH).
      Applying this technique to the gene expression analysis of patients with AMD
      could identify those genes that are involved in molding of the disease.

PMID- 16598468
TI  - Postoperative application of mitomycin c improves the complete success rate of
      primary trabeculectomy: a prospective, randomized trial.
AB  - BACKGROUND: The intraoperative application of mitomycin c for primary
      trabeculectomy is associated with potentially sight-threatening side-effects.
      This study was performed to evaluate the pressure-lowering effect of
      postoperative application of mitomycin c for primary trabeculectomy and to
      evaluate the complications of this new technique. MATERIALS AND METHODS: A
      randomized, prospective clinical trial with 52 consecutive patients scheduled for
      glaucoma surgery in one large surgical center was performed. Patients underwent
      routine trabeculectomy. In group 1, mitomycin c (0.05 mg/ml) was applied
      topically to the filtering bleb for 5 min on the 3 days after surgery
      (postoperative application). In group 2, no mitomycin c was applied (controls).
      The IOP values, visual acuity, number of antiglaucomatous medications and
      complications were evaluated. RESULTS: Follow-up was evaluated up to 24 months
      for all patients. The mean intraocular pressure decreased from 31.1 to 15.4 mmHg
      in group 1 and from 24.8 to 15.6 mmHg in group 2 (P=0.79; t-test). The average
      number of medications decreased from 2.5 and 2.4 to 0.4 and 0.6 (P=0.53; t-test)
      in groups 1 and 2, respectively. No cases of hypotony maculopathy occurred. An
      individual decrease of more than 25% of the IOP was present in 84.6% in group 1
      and in 53.8% in group 2 (P<0.017). Survival analysis for eyes with a complete
      surgical success revealed a better outcome of eyes in group 1 as compared to the
      eyes in group 2 (P<0.013; log-rank test). CONCLUSIONS: To our knowledge, this is
      the first prospective, randomized clinical trial to evaluate the efficacy of
      postoperative mitomycin c application in primary trabeculectomy. The application
      of mitomycin significantly reduced the IOP while not increasing the rate of
      complications.

PMID- 16598469
TI  - Lipid model membranes for drug interaction study.
AB  - The present work shows a structural study on the process of incorporation of a
      hydrophobic drug, Ellipticine (ELPT), into lipid model membranes for drug
      targeting purpose. The ELPT is an alkaloid that showed an anti-proliferation
      activity against several types of tumor cells and against the HIV1 virus. We used
      the zwitterionic lipid dipalmitoyl phosphatidylcholine (DPPC) and four different
      anionic lipids: cardiolipin (CL), dipalmitoyl phosphatidic acid (DPPA),
      dipalmitoyl phosphatidylglycerol (DPPG) and dipalmitoyl phosphatidylserine
      (DPPS), both spread on a Langmuir monolayer and deposited on a solid substrate to
      mimic a model membrane and study the interaction with the drug ELPT. X-ray
      reflectivity results pointed toward an increase in drug loading efficiency up to
      13.5% mol/mol of ELPT into mixed systems DPPC/CL. This increase in loading
      efficiency was also accompanied by a slight distortion in the stacking of the
      bilayers less evidenced after optimization of the molar ratio between the co
      lipids. Grazing incidence X-ray diffraction measurements revealed an in-plane
      lattice distortion due to the presence of hydrocarbon chain backbone ordering in
      pure systems of DPPC doped with ELPT. The same was not observed in mixed
      membranes with DPPC/CL and DPPC/DPPA.

PMID- 16598470
TI  - Carbohydrate components of Taenia crassiceps metacestodes display Th2-adjuvant
      and anti-inflammatory properties when co-injected with bystander antigen.
AB  - Common helminth infections promote Th2-skewed immune responses in their hosts. We
      have studied the role of intact carbohydrate structures on Taenia crassiceps
      compounds in the induction of biased type 2 and anti-inflammatory immune
      responses on peptide-stimulated T cells by using DO11.10 transgenic (OVA Tg)
      mice. While OVA Tg mice co-injected with OVA peptide (323-339) (OVA(323-339))
      plus intact Taenia soluble antigens (iTSA) displayed significantly higher titers
      of OVA-specific IgG1 and total IgE, low amounts of these antibodies were
      detectable in sera from OVA Tg mice co-injected with OVA(323-339) plus periodate
      carbohydrate altered TSA (paTSA). Spleen cells from OVA Tg mice failed to
      efficiently produce OVA-specific IFN-gamma but displayed higher IL-4, IL-5 and IL
      10 production when they received OVA(323-339) plus iTSA, compared with OVA Tg
      mice similarly co-injected with OVA(323-339) plus paTSA. Moreover, after in vivo
      stimulation with OVA(323-339) plus iTSA, spleen cells did show elevated mRNA
      transcripts for Arginase 1, Ym1, IL-4, IL-10, TGF-beta, and Mannose Receptor (MR)
      genes, all them associated with Th2-type and anti-inflammatory responses. Similar
      results were obtained using TLR4 mutant mice. Together these findings suggest
      that carbohydrate components in TSA are involved in modulating immune responses
      to bystander antigens and that do not signal via TLR4.

PMID- 16598471
TI  - Giardia lamblia cysteine proteases.

PMID- 16598473
TI  - Solid pelvic tumor in a woman with Mayer-Rokitansky-Kustner-Hauser syndrome.
AB  - A patient with Mayer-Rokitansky-Kustner-Hauser syndrome was operated
      laparoscopically to remove a solid pelvic tumor with cystic region, originally
      diagnosed as an ovarian tumor. Histopathological examination of the removed tumor
      identified it as a leiomyoma of rudimentary uterus.

PMID- 16598474
TI  - Adnexal torsion in a patient with bichorial twin pregnancy in the 21st week of
      gestation treated by open laparoscopy: a case report.
AB  - Adnexal torsion is a rare finding during pregnancy. Here we report a patient with
      bichorial twin pregnancy in the 21st week of gestation with adnexal torsion. She
      was admitted with acute abdominal pain. Open laparoscopy was performed and the
      left adnexa was unwinded successfully. The postoperative follow-up was
      uneventful. Adnexal torsion as differential diagnosis of acute abdomen in
      pregnancy should be considered seriously to avoid irreversible lesions of the
      ovary and (salpingo-) oophorectomy.

PMID- 16598472
TI  - Coagulase-negative staphylococci in very-low-birth-weight infants: inability of
      genetic markers to distinguish invasive strains from blood culture contaminants.
AB  - Selected coagulase-negative staphylococci from the blood of very-low-birth-weight
      infants in the Neonatal Intensive Care Unit at the Royal Women's Hospital,
      Melbourne, collected over a 5-year period were examined. Isolates were classified
      as invasive or contaminants, speciated, typed by pulsed-field gel
      electrophoresis, and examined for biofilm genes (icaA, icaC, and icaD), adhesion
      genes (atlE, fbe), and the number of copies of IS256. Of the 24 isolates studied,
      there were 13 contaminants and 11 invasive isolates. The collection included 15
      Staphylococcus epidermidis, eight Staphylococcus capitis, and one each of
      Staphylococcus warneri and Staphylococcus haemolyticus. Two small clusters of S.
      epidermidis that belonged to the same molecular type were identified. All S.
      capitis isolates belonged to the same molecular type or subtype, suggesting that
      a particular clone was circulating in the unit. There was no significant
      difference in the species found, the presence of icaA, icaC, icaD, atlE, or fbe,
      or the number of copies of IS256 between invasive isolates and contaminants. A
      series of nasal isolates from nonhospitalized adults differed from hospital
      isolates in the absence of IS256 and the low prevalence of icaC. There was no
      evidence of IS256-mediated insertion into ica genes as a mechanism of phase
      variation. These findings suggest that contaminants and invasive isolates derived
      from the same pool of hospital strains capable of causing sepsis in compromised
      hosts and that other mechanisms of phase variation exist, apart from IS256
      insertion into ica genes.

PMID- 16598475
TI  - Interaction between BRCA1 and human papilloma virus E7: an ontology study.
AB  - BRCA1 was the first breast cancer susceptibility gene to be identified and
      cloned. Recent studies indicate that BRCA 1 interacts with and regulates the
      activity of estrogen receptor alpha. The correlation between BRCA1 and E7 of
      papilloma virus becomes a new interesting topic in gynecological cancer.
      According to this study, E7 can add no function or aberration to the BRCA1
      molecule. Further experimental studies are needed before making a conclusion on
      this topic. The finding in this study not only supports the previous knowledge on
      BRCA1 but also gives a new view on the function of BRCA1 and E7 in breast cancer.
      Here, the author used a new gene ontology technology to predict the molecular
      function and biological process of BRCA1 and E7.

PMID- 16598476
TI  - Anticoagulation therapy during pregnancy of patients with artificial heart
      valves: fetomaternal outcome.
AB  - OBJECTIVES: The major problem is the need for anticoagulant therapy in patient
      with mechanical heart valves. STUDY DESIGN: The aim of the study was to analyze
      the course and outcome of pregnancies of patients with artificial mechanical
      heart valves with anticoagulant therapy. Study included 43 pregnancies leaded and
      terminated at the Institute of Gynecology and Obstetrics Clinical Center of
      Serbia in 20 years. We divided the patients in two groups depending on the type
      of anticoagulation therapy. Group I included 21 patients who were under
      Ethylbiscumacetate (Pelenthan) during the first 36 weeks of gestation, and
      intravenous Heparin in the last 4 weeks and after the delivery. Group II included
      22 patients who received oral anticoagulant therapy all the time. RESULTS:
      Worsening of the heart functional status happened in 6 patients (13.9%). The
      incidence of heart failure during the pregnancy was 13.9% and after the delivery
      9.3%. The incidence of hemorrhagic complications was 11.6% during pregnancy and
      14% after the delivery. Four patients had thromboembolic events before the
      pregnancy. The incidence of postpartal thromboembolic complications was 6.9% in
      group I. Two patients died due to the heart failure 3-7 days after the vaginal
      delivery. Maternal mortality was 4.6%. One neonatus died of hydrocephalus (2.5%)
      in group II. In our study there were no fetuses with congenital heart disease.
      CONCLUSIONS: Pregnancies of patients with mechanical heart valves should be
      planned. We suggest ethylbiscumacetate in combination with Heparin as
      anticoagulation therapy during the pregnancy.

PMID- 16598477
TI  - Heterotopic pregnancy: a rare cause of hemoperitoneum and the acute abdomen.
AB  - INTRODUCTION: Heterotopic pregnancy is the rare coexistence of intrauterine and
      extrauterine gestation. The incidence may be as high as 1 in 3,889 pregnancies.
      The diagnosis is difficult to make, but an important one to consider in the
      presence of acute abdominal pain, hemorrhagic shock, and intrauterine pregnancy.
      METHODS: Case report. RESULTS: Successful treatment of ectopic pregnancy with
      benign convalescence and viable intrauterine pregnancy delivered at term.
      CONCLUSIONS: Every clinician treating women of reproductive age should keep this
      diagnosis in their differential, especially for pregnant women presenting with
      abdominal pain and hemoperitoneum.

PMID- 16598478
TI  - A comparison of the accuracy of two minimally invasive breast biopsy methods: a
      systematic literature review and meta-analysis.
AB  - OBJECTIVE: The primary objective was to quantify and compare the accuracy and
      failure rates of directional vacuum assisted biopsy (DVAB) and core needle biopsy
      (CNB) when used under stereotactic (ST) guidance to biopsy suspicious breast
      lesions identified with screening mammography. METHODS: We performed a systematic
      review of the literature published from January 1996 to July 2004, reporting all
      comers populations in Western-style health care systems (i.e., North America,
      Europe, Australia or New Zealand), referred after screening mammography for
      breast biopsy using DVAB or CNB under ST guidance. Meta-analyses were conducted
      for DVAB and CNB, using open surgical biopsy and/or long-term clinical and/or
      mammogram follow-up as the diagnostic reference standard. The main outcomes of
      interest were those of greatest clinical relevance, i.e., miss rates and
      underestimation rates for malignancy. Also, technical failure rate and non
      diagnostic rate were assessed for each biopsy method. RESULTS: Thirty-five
      studies qualified for the review. There were 12 studies with a DVAB group
      (n=5,119 patients), and 25 studies with a CNB group (n=6,236). There were no
      studies including both a DVAB and a CNB group, thus precluding any direct, within
      study comparisons of accuracy. Overall agreement rate between DVAB and the
      reference standard was 97.3%, and between CNB and the reference standard, 93.5%.
      The frequency of technical failures with CNB was slightly higher than DVAB (5.7
      vs. 1.5%), as was the frequency of non-diagnostic samples (2.1 vs. 0%). Of the
      non-diagnostic CNB samples, 23% were subsequently found to be malignant on
      reference standard. In multivariate analyses using four covariates (procedure
      type, geographic location, reference standard, and patient position), there were
      no significant predictors of agreement rates, but some variables were significant
      predictors of miss rates. For benign to malignant upgrades, study location was a
      significant predictor, with more upgrades in non-NA locations. For atypia to
      malignant upgrades, the type of procedure was a significant predictor, with more
      underestimations in CNB studies. CONCLUSION: The best available evidence suggests
      that, in screening populations referred for minimally invasive breast biopsy
      biopsy requiring ST guidance, DVAB may provide lower miss and underestimation
      rates for clinically relevant diagnoses than does CNB.

PMID- 16598479
TI  - Regional brain metabolite abnormalities in inherited prion disease and
      asymptomatic gene carriers demonstrated in vivo by quantitative proton magnetic
      resonance spectroscopy.
AB  - INTRODUCTION: Inherited prion diseases are caused by mutations in the gene which
      codes for prion protein (PrP), leading to proliferation of abnormal PrP isomers
      in the brain and neurodegeneration; they include Gerstmann-Straussler-Scheinker
      disease (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob
      disease (fCJD). METHODS: We studied two patients with symptomatic inherited prion
      disease (P102L) and two pre-symptomatic P102L gene carriers using quantitative
      magnetic resonance spectroscopy (MRS). Short echo time spectra were acquired from
      the thalamus, caudate region and frontal white matter, metabolite levels and
      ratios were measured and z-scores calculated for individual patients relative to
      age-matched normal controls. MRS data were compared with structural magnetic
      resonance imaging. RESULTS: One fCJD case had generalised atrophy and showed
      increased levels of myo-inositol (MI) in the thalamus (z=3.7). The other had
      decreased levels of N-acetylaspartate (z=4) and diffuse signal abnormality in the
      frontal white matter. Both asymptomatic gene carriers had normal imaging, but
      increased frontal white matter MI (z=4.3, 4.1), and one also had increased MI in
      the caudate (z=5.3). CONCLUSION: Isolated MI abnormalities in asymptomatic gene
      carriers are a novel finding and may reflect early glial proliferation, prior to
      significant neuronal damage. MRS provides potential non-invasive surrogate
      markers of early disease and progression in inherited prion disease.

PMID- 16598480
TI  - Delayed coil migration from a small wide-necked aneurysm after stent-assisted
      embolization: case report and literature review.
AB  - INTRODUCTION: We present a previously unreported complication following the
      treatment of a patient with two small, wide-necked, posterior communicating
      artery aneurysms. METHODS: Endovascular embolization of one aneurysm was
      performed using a stent-assisted technique. Follow-up angiography 5 months later
      revealed that a coil had escaped the confinement of the stent and migrated
      distally without occluding any arterial branches or causing symptoms. This case
      report demonstrates that although a rare occurrence, a coil can break loose from
      the stent. DISCUSSION: We discuss the potential mechanisms of this phenomenon and
      review the literature on stent-assisted aneurysm coiling in order to raise
      awareness of this event when embolizing small, wide-necked aneurysms with a stent
      assisted technique.

PMID- 16598481
TI  - Thermal and flow measurements of continuous cryogenic spray cooling.
AB  - The performance of single sprays for high heat flux cooling using R-134a was
      studied. The heat flux and heat transfer coefficient at the surface of a sprayed
      jet based on measurements of steady-state temperature gradients on a thin copper
      plate during continuous spraying. Meanwhile, the spray droplets flow
      characteristics was also quantified through laser doppler velocimetry (LDV)
      measurements to obtain the local velocity distributions. The effects of mass flow
      rate and average droplet velocity, and spray exit-to-target distance on the
      surface heat flux including the corresponding critical heat flux (CHF) were
      explored through three different nozzle diameters of 0.2, 0.3, and 0.4 mm.
      Finally, the effective use of the fluid being delivered based on the cooling
      efficiency and cooling effectiveness was also examined. The relationship between
      CHF and nozzle performance in terms of cooling efficiency and cooling
      effectiveness was found. The heat transfer removal rate can reach up to 140
      W/cm(2) for the present nozzle size of d (j)=0.2 and 0.3 mm, which may enhance
      the current cryogen spray cooling (CSC) technique that assists laser therapy of
      dermatoses.

PMID- 16598482
TI  - Seasonality of weather and tree phenology in a tropical evergreen mountain rain
      forest.
AB  - Flowering and fruiting as phenological events of 12 tree species in an evergreen
      tropical mountain rain forest in southern Ecuador were examined over a period of
      3-4 years. Leaf shedding of two species was observed for 12 months. Parallel to
      the phenological recordings, meteorological parameters were monitored in detail
      and related to the flowering and fruiting activity of the trees. In spite of the
      perhumid climate of that area, a high degree of intra- and inter-specific
      synchronisation of phenological traits was apparent. With the exception of one
      species that flowered more or less continuously, two groups of trees could be
      observed, one of which flowered during the less humid months (September to
      October) while the second group started to initiate flowers towards the end of
      that phase and flowered during the heavy rains (April to July). As reflected by
      correlation coefficients, the all-time series of meteorological parameters showed
      a distinct seasonality of 8-12 months, apparently following the quasi-periodic
      oscillation of precipitation and related cloudiness. As revealed by power
      spectrum analysis and Markov persistence, rainfall and minimum temperature appear
      to be the only parameters with a periodicity free of long-term variations. The
      phenological events of most of the plant species showed a similar periodicity of
      8-12 months, which followed the annual oscillation of relatively less and more
      humid periods and thus was in phase or in counter-phase with the oscillations of
      the meteorological parameters. Periods of unusual cold or dryness, presumably
      resulting from underlying longer-term trends or oscillations (such as ENSO),
      affected the homogeneity of quasi-12-month flowering events, fruit maturation and
      also the production of germinable seeds. Some species show underlying quasi-2
      year-oscillations, for example that synchronise with the development of air
      temperature; others reveal an underlying decrease or increase in flowering
      activity over the observation period, influenced for instance by solar
      irradiance. As Ecuador suffers the highest rate of deforestation in South
      America, there is an urgent need for indigenous plant material for reforestation.
      A detailed knowledge of the biology of reproduction in relation to governing
      external factors (mainly climate) is thus required.

PMID- 16598483
TI  - Does Botox effect neural tube development in early chick embryos?
AB  - Botulinum toxin (BTX) is a potent neurotoxin produced by Clostridium botulinum
      and has wide usage in different areas. The current study aimed to analyze the
      effects of C. botulinum toxin on the central nerve system in chick embryos. Forty
      fertile Hubbard Broil eggs, all at Stage 8 of development, were divided into four
      equal groups: Group 1 embryos (n=10), the control group, were explanted and grown
      for 18 h in a nutrient medium (thin albumin). Group 2 embryos (n=10) were grown
      in medium containing 5 U BTX, Group 3 embryos (n=10) in a medium containing 10 U
      BTX and Group 4 embryos (n=10) in medium containing 20 U BTX. After the
      incubation period, 80% of Group 1 and 2 embryos and 90% of Group 3 and 4 embryos
      had intact neural tubes (P>0.05). The results of this study suggest that BTX had
      no additional effect on neural tube development in early chick embryos.

PMID- 16598484
TI  - Harvesting local cylinder autograft from adjacent vertebral body for anterior
      lumbar interbody fusion: surgical technique, operative feasibility and
      preliminary clinical results.
AB  - Autogenous iliac crest has long served as the gold standard for anterior lumbar
      arthrodesis although added morbidity results from the bone graft harvest.
      Therefore, femoral ring allograft, or cages, have been used to decrease the
      morbidity of iliac crest bone harvesting. More recently, an experimental study in
      the animal showed that harvesting local bone from the anterior vertebral body and
      replacing the void by a radio-opaque beta-tricalcium phosphate plug was a valid
      concept. However, such a concept precludes theoretically the use of posterior
      pedicle screw fixation. At one institution a consecutive series of 21 patients
      underwent single- or multiple-level circumferential lumbar fusion with anterior
      cages and posterior pedicle screws. All cages were filled with cancellous bone
      harvested from the adjacent vertebral body, and the vertebral body defect was
      filled with a beta-tricalcium phosphate plug. The indications for surgery were
      failed conservative treatment of a lumbar degenerative disc disease or
      spondylolisthesis. The purpose of this study, therefore, was to report on the
      surgical technique, operative feasibility, safety, benefits, and drawbacks of
      this technique with our primary clinical experience. An independent researcher
      reviewed all data that had been collected prospectively from the onset of the
      study. The average age of the patients was 39.9 (26-57) years. Bone grafts were
      successfully harvested from 28 vertebral bodies in all but one patient whose
      anterior procedure was aborted due to difficulty in freeing the left common iliac
      vein. This case was converted to a transforaminal interbody fusion (TLIF). There
      was no major vascular injury. Blood loss of the anterior procedure averaged 250
      ml (50-350 ml). One tricalcium phosphate bone plug was broken during its
      insertion, and one endplate was broken because of wrong surgical technique, which
      did not affect the final outcome. One patient had a right lumbar plexopathy that
      was not related to this special technique. There was no retrograde ejaculation,
      infection or pseudoarthrosis. One patient experienced a deep venous thrombosis.
      At the last follow up (mean 28 months) all patients had a solid lumbar spine
      fusion. At the 6-month follow up, the pain as assessed on the visual analog scale
      (VAS) decreased from 6.9 to 4.5 (33% decrease), and the Oswestry disability index
      (ODI) reduced from 48.0 to 31.7 with a 34% reduction. However, at 2 years follow
      up there was a trend for increase in the ODI (35) and VAS (5). The data in this
      study suggest that harvesting a cylinder of autograft from the adjacent vertebral
      body is safe and efficient. Filling of the void defect with a beta-tricalcium
      phosphate plug does not preclude the use of posterior pedicle screw
      stabilization.

PMID- 16598485
TI  - Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies
      using tissue microarray technology.
AB  - We performed a systematic immunohistochemical study on 378 brain tumors using 37
      antibodies and tissue microarray (TMA) technology. The aim of this study was to
      find new diagnostic biomarkers using antibodies established in our laboratory.
      Our TMA consisted of a grid of 1.5-mm cores that were extracted from individual
      donor blocks. Staining for each antibody was scored using a three-point system.
      We used hierarchical clustering analysis to interpret these data, which resulted
      in separation of all the brain tumors into seven groups. Although there were some
      exceptions, cases with the same histological diagnosis were generally grouped
      together. We then carried out statistical analyses to find the most useful
      antibodies for grouping of brain tumors. Ten antibodies [glial fibrillary acidic
      protein (GFAP), Olig2, vimentin, epithelial membrane antigen (EMA), cytokeratin
      (AE1/AE3), alpha-internexin, nestin, pinealocytes PP5, aquaporin-4 (AQP4) M13d
      and AQP4M13e] discriminated between astrocytomas and oligodendroglial tumors. Six
      antibodies [EMA, AE1/AE3, TUJ1, nestin, neurofilament protein-MH (NF-MH) and
      perivascular cells GP-1] showed significant differences between high-grade and
      low-grade gliomas. Our data have revealed new antibodies with potential
      diagnostic utility (Olig2, PP5, GP-1) and demonstrate that TMA technology is
      highly useful for evaluating newly established antibodies in brain-tumor
      research.

PMID- 16598486
TI  - Environmental and genetic components of oxidative stress in wild kestrel
      nestlings (Falco tinnunculus).
AB  - In this study, we estimated the environmental and genetic components of two
      variables related to avian oxidative stress using wild nestlings of the Eurasian
      kestrel (Falco tinnunculus). The study was carried out during two breeding
      seasons. In the first season, we assessed the between- and within-nest
      resemblance in serum reactive oxygen metabolites (ROMs) and total serum
      antioxidant barrier (OXY). In the second season, we carried out a cross-fostering
      experiment to determine the importance of environmental and genetic factors on
      ROMs and OXY. The 23.5% of ROMs variance was explained by the nest of origin,
      indicating a main genetic component. In contrast, the 52.8% of OXY variance was
      explained by the nest of rearing, indicating that this variable was more
      influenced by environmental components. These findings suggest that variations in
      ROMs and OXY could reflect, respectively, the expression of different genetic
      polymorphisms and differences in dietary uptake of antioxidants.

PMID- 16598488
TI  - [The TNK ankle: short- and mid-term results].
AB  - Total ankle replacement has been introduced in the last 30 years. The TNK ankle
      is build from ceramics, and it was continuously improved. This prosthesis has the
      longest fellow-up times. Seventy ankle prostheses of the newest generation has
      been implanted between 1991 and 2001. Of these, 67 prostheses were assessed
      clinically and radiographically after 62 months (range, 24 to 132 months). Three
      ankles have been revised. The clinical score improved for the patients with
      primary or posttraumatic arthritis from 34 to 86, and for the patients with
      rheumatoid arthritis from 45 to 74. Loosening was found in 4 ankles with non
      rheumatoid arthritis, and in 17 ankles with rheumatoid ankles. Total ankle
      replacement has emerged to a valuable alternative to ankle arthrodesis, and
      satisfactory results have been achieved with the current implants. The bone
      implant interphase might play a most important factor for success. There is
      evidence that the biologic advantages of ceramics may help to improve long
      lasting success in total ankle replacement.

PMID- 16598487
TI  - [Early functional treatment of congenital clubfoot].
AB  - The concept of conservative clubfoot treatment beginning in the neonatal period
      has changed considerably in the last 2 decades. The rate of clubfeet requiring
      surgery (20%) and the extent of surgical interventions have dropped
      significantly. The early functional Montpellier method has proved to be highly
      effective for all degrees of deformity. It is used for patients from birth until
      the age of 1 year. The treatment during the first 3 months of life is decisive
      and consists of daily physical therapy, use of a continuous passive motion
      machine, and taping. This method represents an efficient alternative to the
      popular treatment of serial casting. Nevertheless, conservative clubfoot
      treatment reaches its limits as the degree of deformity increases and it should
      be complemented by a selective minimally invasive surgical concept. The technique
      is described systematically and its current value is discussed.

PMID- 16598489
TI  - [The HINTEGRA ankle: short- and mid-term results].
AB  - The HINTEGRA ankle was developed as an attempt to specifically address the needs
      of minimal bone resection, extended bone support, proper ligament balancing, and
      minimal contact stresses within and around the prosthesis. The purpose of this
      article was to present the design and rationale of this prosthesis, and to
      analyze the clinical and radiological short- to mid-term results particularly
      with respect to the revisions and learning curve. Of the 278 total ankle
      replacements (between 2000 and 2004) with the HINTEGRA ankle, 271 ankles
      [patients: 261, males: 133, females: 128, age: 58.4 years (range: 25-90 years)]
      were clinically and radiographically assessed after 36.1 months (range: 12-64
      months). The preoperative diagnosis was post-traumatic osteoarthrosis in 206
      cases (76.0%), systemic arthritis in 34 cases (12.5%), and a primary
      osteoarthrosis in 31 cases (11.5%). Beside 4 perioperative and 19 early
      postoperative complications, a late complication occurred in 40 cases (14.8%). Of
      these, 22 complications (8.2%) were not related to implants, and 18 complications
      (6.6%) were related to implants. In all, 39 cases (14.4%) were revised; of these,
      5 cases (1.8%) were revised to ankle arthrodesis. All other 34 revision
      arthroplasties were successful and did not evidence any differences in the
      outcome to the non-revised ankles. The AOFAS hindfoot score improved from 40.3
      (range: 14-61) to 85.0 (range: 44-100) points at last follow-up.
      Radiographically, the tibial component was stable in all remaining 266 ankles,
      and no tilting of the component occurred since surgery. The talar component was
      positioned too posteriorly in 12 ankles (4.4%). The concept of minimal bone
      resection and wide bony support was shown to be successful on the tibial and
      talar sides. Most complications occurred in the early cases of this series, and
      the learning curve was found to be short and steep. Despite the high amount of
      post-traumatic cases with limited soft tissue quality, the obtained function,
      pain relief, and patient satisfaction were promising and, compared with other
      devices, the results mostly were superior. This may support the belief that
      anatomically shaped surfaces, as is the case in the HINTEGRA ankle, may advance
      success in total ankle replacement.

PMID- 16598491
TI  - [The AGILITY ankle: mid- and long-term results].
AB  - The AGILITY ankle has been clinically used for over 20 years and between the two
      authors, a total of 1,075 AGILITY ankles have been inserted. Beside concept and
      design of this unique ankle prosthesis, specific follow-up data will be presented
      on 775 implants performed by the first author (FGA). The AGILITY Ankle System can
      give reliable and predictable results if the surgeon is aware of the complexity
      of this operation and the need for careful postoperative monitoring. Many of the
      failures that have occurred in the Agility System can be prevented by early
      detection (i.e., syndesmotic nonunion, hindfoot valgus, fractures, etc.) and if
      the problem is corrected, the implant can be maintained. The new LP System will
      also add another dimension to the overall adaptability of the prosthesis for an
      additional broader base of patients.

PMID- 16598490
TI  - [Single- and double-coated star total ankle replacements: a clinical and
      radiographic follow-up study of 109 cases].
AB  - An up to 12-year follow-up of 51 single-coated STAR revealed that 15 ankles had
      undergone fusion. The mean time from primary surgery to the first revision was
      median 51 months. In a series of 58 double-coated STAR ankles followed up to 5
      years only one ankle had to be revised for component loosening. In this series
      the clinical survival rate was 98% and the radiographic survival rate 94% at 5
      years. The radiographic survival rate, with component loosening as endpoint, was
      significantly better for the last 31 cases in the series of the single-coated
      prostheses. However, the loosening rate did not differ when these latter 31 cases
      were compared with the cases operated on with a double-coated prosthesis. One may
      conclude that improvement of the anchoring surfaces has had a limited influence
      on the radiographic survival of the STAR ankle. However, from the clinical
      survivorship figures it is obvious that the learning process continues as the
      difference in revision rate between the 31 last implanted single-coated and the
      later on implanted double-coated prostheses approached significance.

PMID- 16598492
TI  - A bimodular theory for finite deformations: Comparison of orthotropic second
      order and exponential stress constitutive equations for articular cartilage.
AB  - Cartilaginous tissues, such as articular cartilage and the annulus fibrosus,
      exhibit orthotropic behavior with highly asymmetric tensile-compressive
      responses. Due to this complex behavior, it is difficult to develop accurate
      stress constitutive equations that are valid for finite deformations. Therefore,
      we have developed a bimodular theory for finite deformations of elastic materials
      that allows the mechanical properties of the tissue to differ in tension and
      compression. In this paper, we derive an orthotropic stress constitutive equation
      that is second-order in terms of the Biot strain tensor as an alternative to
      traditional exponential type equations. Several reduced forms of the bimodular
      second-order equation, with six to nine parameters, and a bimodular exponential
      equation, with seven parameters, were fit to an experimental dataset that
      captures the highly asymmetric and orthotropic mechanical response of cartilage.
      The results suggest that the bimodular second-order models may be appealing for
      some applications with cartilaginous tissues.

PMID- 16598493
TI  - New drugs from marine microbes: the tide is turning.
AB  - This is a mini-review demonstrating that investigation of the genomics of marine
      microbes from all three domains has the potential to revolutionize the search for
      secondary metabolites originally thought to be the product of marine
      invertebrates. The basis for the review was a symposium at the 2005 Annual
      Meeting of the SIM covering some aspects of the potential for marine microbes to
      be the primary producers of such metabolites. The work reported at that symposium
      has been integrated into a fuller discussion of current published literature on
      the subject with examples drawn from bacteria, cyanophytes and fungi.

PMID- 16598494
TI  - Lanthanum biosorption by a Pseudomonas sp.: equilibrium studies and chemical
      characterization.
AB  - Lanthanum biosorption by a Pseudomonas sp. was characterized in terms of
      equilibrium metal loading, model fitting, kinetics, effect of solution pH,
      lanthanum-bacteria interaction mechanism and recovery of sorbed metal. Lanthanum
      sorption by the bacterium was rapid and optimum at pH 5.0 with equilibrium metal
      loading as high as 950 mg g(-1) biomass dry wt. Scatchard model and
      potentiometric titration suggested the presence of at least two types of metal
      binding sites, corresponding to a strong and a weak binding affinity. The
      chemical nature of metal-microbe interaction has been elucidated employing FTIR
      spectroscopy, energy dispersive X-ray analysis (EDX) and X-ray diffraction
      analysis (XRD). FTIR spectroscopy and XRD analysis revealed strong involvement of
      cellular carboxyl and phosphate groups in lanthanum binding by the bacterial
      biomass. EDX and the elemental analysis of the sorption solution ascertained the
      binding of lanthanum with the bacterial biomass via displacement of cellular
      potassium and calcium. Transmission electron microscopy exhibited La accumulation
      throughout the bacterial cell with some granular deposits in cell periphery and
      in cytoplasm. XRD confirmed the presence of LaPO4 crystals onto the bacterial
      biomass after La accumulation for a long period. A combined ion-exchange
      complexation-microprecipitation mechanism could be involved in lanthanum
      accumulation by the biomass. Almost 98% of biomass-bound La could be recovered
      using CaCO3 as the desorbing agent.

PMID- 16598495
TI  - Effect of pyridostigmine, pralidoxime and their combination on survival and
      cholinesterase activity in rats exposed to the organophosphate paraoxon.
AB  - Pyridostigmine (PSTG) is a carbamate inhibitor of cholinesterases. Carbamates are
      known to confer some protection from the lethal effects of (some)
      organophosphorus compounds. Recently, based on animal data, the FDA approved oral
      PSTG for pre-exposure treatment of soman. The purpose of the study was to
      quantify in vivo the effect of PSTG pre-treatment on survival in rats exposed to
      the organophosphate paraoxon (POX) with and without subsequent reactivator
      (pralidoxime) treatment. POX is a highly toxic non-neuropathic ethyl
      organophospate. Pralidoxime (PRX) is the enzyme reactivator used by some NATO
      armies. The prospective, controlled animal (rat) study included Group 1 that
      received 1 micromol POX ( approximately LD(75)); Group 2 that received 1 micromol
      PSTG followed 30 min later by 1 micromol POX; Group 3 that received 1 micromol
      PSTG followed 30 min later by 1 micromol POX and 50 micromol PRX; Group 4 that
      received 1 micromol POX and 50 micromol PRX; Group 5 that received 1 micromol
      PSTG; Group 6 that received 50 micromol PRX and Group 7 that received 1 micromol
      PSTG followed 30 min later by 50 micromol PRX. Each group contained six rats. The
      experiment was repeated twelve times (12 cycles). All substances were applied
      i.p. From surviving animals of eight cycles tail blood was taken for red blood
      cell acetylcholinesterase (RBC-AChE) measurements. The animals were monitored for
      48 h and mortality (survival time) was recorded. RBC-AChE activities were
      determined. Mortality was analysed using Kaplan-Meier plots. Both PSTG and PRX
      statistically significantly decreased organophosphate induced mortality in the
      described model. While the same applies to their combination the decrease in
      mortality when using both PSTG and PRX is less than that achieved with their
      single use (but not significantly so). While certainly further work using
      different organophosphorus compounds and animal species are needed before a final
      conclusion is reached, the animal data presented does not support the combined
      use of PSTG and PRX.

PMID- 16598496
TI  - High concordance of drug-induced human hepatotoxicity with in vitro cytotoxicity
      measured in a novel cell-based model using high content screening.
AB  - To develop and validate a practical, in vitro, cell-based model to assess human
      hepatotoxicity potential of drugs, we used the new technology of high content
      screening (HCS) and a novel combination of critical model features, including (1)
      use of live, human hepatocytes with drug metabolism capability, (2) preincubation
      of cells for 3 days with drugs at a range of concentrations up to at least 30
      times the efficacious concentration or 100 microM, (3) measurement of multiple
      parameters that were (4) morphological and biochemical, (5) indicative of
      prelethal cytotoxic effects, (6) representative of different mechanisms of
      toxicity, (7) at the single cell level and (8) amenable to rapid throughput. HCS
      is based on automated epifluorescence microscopy and image analysis of cells in a
      microtiter plate format. The assay was applied to HepG2 human hepatocytes
      cultured in 96-well plates and loaded with four fluorescent dyes for: calcium
      (Fluo-4 AM), mitochondrial membrane potential (TMRM), DNA content (Hoechst
      33,342) to determine nuclear area and cell number and plasma membrane
      permeability (TOTO-3). Assay results were compared with those from 7
      conventional, in vitro cytotoxicity assays that were applied to 611 compounds and
      shown to have low sensitivity (<25%), although high specificity ( approximately
      90%) for detection of toxic drugs. For 243 drugs with varying degrees of
      toxicity, the HCS, sublethal, cytotoxicity assay had a sensitivity of 93% and
      specificity of 98%. Drugs testing positive that did not cause hepatotoxicity
      produced other serious, human organ toxicities. For 201 positive assay results,
      86% drugs affected cell number, 70% affected nuclear area and mitochondrial
      membrane potential and 45% affected membrane permeability and 41% intracellular
      calcium concentration. Cell number was the first parameter affected for 56% of
      these drugs, nuclear area for 34% and mitochondrial membrane potential for 29%
      and membrane permeability for 7% and intracellular calcium for 10%. Hormesis
      occurred for 48% of all drugs with positive response, for 26% of mitochondrial
      and 34% nuclear area changes and 12% of cell number changes. Pattern of change
      was dependent on the class of drug and mechanism of toxicity. The ratio of
      concentrations for in vitro cytotoxicity to maximal efficaciousness in humans was
      not different across groups (12+/-22). Human toxicity potential was detected with
      80% sensitivity and 90% specificity at a concentration of 30x the maximal
      efficacious concentration or 100 microM when efficaciousness was not considered.
      We conclude that human hepatotoxicity is highly concordant with in vitro
      cytotoxicity in this novel model and as detected by HCS.

PMID- 16598497
TI  - Primary central nervous system non-Hodgkin lymphoma in childhood presenting as
      bilateral optic neuritis.
AB  - INTRODUCTION: Primary central nervous system lymphoma is a very rare condition in
      pediatric patients. CASE REPORT: We describe the case of a 10-year old girl who
      presented with acute bilateral vision impairment. At the time of presentation,
      the only positive finding was optic disk swelling, and the brain MRI scan was
      normal. Seventeen months later, she developed a large-cell non-Hodgkin lymphoma
      in the brain, with no evidence of neoplasia elsewhere. Immunodeficiencies and
      Epstein-Barr virus infection could not be demonstrated. The patient was
      successfully treated with a combination of cyclophosphamide, etoposide,
      vincristine, methotrexate, and cytarabine, plus intrathecal chemotherapy.
      Craniospinal irradiation was not used. OUTCOME: The patient's condition is still
      in remission 68 months after completing the treatment. CONCLUSION: This case is
      the only non-Hodgkin lymphoma with primary central nervous system location
      treated in our institution in the last 10 years and represents less than 0.5% of
      our non-Hodgkin lymphoma series. Due to its rare occurrence, not much is known
      about the clinical features and treatment outcome of primary central nervous
      system lymphoma in pediatric patients.

PMID- 16598498
TI  - Pediatric golf-related head injuries.
AB  - OBJECTIVES: Golf-related head injuries constitute an increasingly common
      mechanism of head trauma in children. We present our experience with 33 pediatric
      cases of golf-associated head injury, with special emphasis in the type of
      injury, management strategy, and outcome. MATERIALS AND METHODS: A thorough
      review of all children admitted to our hospital with golf-related head injury
      during a period of 10 years (1 January 1994 to 31 December 2003) was undertaken.
      The patients' charts, operative reports, imaging studies, and follow-up data were
      analyzed. A comparison of our findings with those described in the pertinent
      literature was subsequently performed. CONCLUSIONS: Pediatric golf-related head
      trauma is a significant cause of sport-associated head injury, sometimes
      harboring a very dismal prognosis. The significance of establishing a task force
      for the prevention of these injuries cannot be overemphasized.

PMID- 16598500
TI  - Caspase activation throughout the first wave of spermatogenesis in the rat.
AB  - Early in postnatal life, the first wave of spermatogenesis is accompanied by an
      initial wave of germ cell apoptosis. This may reflect an adjustment in the number
      of germ cells that can be adequately maintained by Sertoli cells. Two major
      pathways (intrinsic and extrinsic) are involved in the process of caspase
      activation and apoptosis in mammalian cells. The extrinsic pathway is
      characterized by the oligomerization of death receptors such as FAS or tumor
      necrosis factor, followed by the activation of caspase-8 and caspase-3. The
      intrinsic pathway involves the activation of procaspase-9, which in turn
      activates caspase-3. Extensive information is available concerning apoptotic
      inducers and their possible mechanisms in the adult rat. However, no data exist
      regarding the molecular and cellular mechanisms governing physiological cell
      death during puberty in the male rat. We have studied caspase activation
      throughout the first wave of spermatogenesis in the rat under physiological
      conditions, by combining the TUNEL procedure with the localization of active
      caspases in germ cells. We observed TUNEL-positive germ cells in rats of 5-40
      days of age, the highest number being found in 25-day-old rats. TUNEL-positive
      and caspase-3-positive germ cells appeared as long chains of interconnected germ
      cells in 25-day-old rats. Caspase activation was assayed by either
      immunohistochemistry with antibodies against active caspase-3, -8, and -9, or by
      determining enzymatic activity in seminiferous tubules extracts. Both techniques
      showed activation of caspase-3, -8, and -9 in 25-day-old rats and low enzymatic
      activity at other ages. Confocal scanning laser microscopy indicated that active
      caspase-3, -8, and -9 co-localized with TUNEL-positive cells. Thus, caspase-3, 
      8, and -9 are active in apoptotic germ cells during the first wave of rat
      spermatogenesis. The extrinsic pathway of apoptosis may therefore play an
      important role in germ cell apoptosis during puberty in the rat.

PMID- 16598501
TI  - Endogenous nitric oxide/cGMP signalling in the guinea pig bladder: evidence for
      distinct populations of sub-urothelial interstitial cells.
AB  - We have examined structures that may operate by using nitric oxide (NO)/soluble
      guanylyl cyclase (sGC) signalling in the lamina propria of the guinea pig
      bladder. Cells on the luminal surface of the urothelium and sub-urothelial
      interstitial cells (SU-ICs) responded to NO with a rise in cGMP. The distribution
      of these different cells varied between the base, lateral wall and dome. In the
      base, two regions were identified: areas with sparse surface urothelial cells and
      areas with a complete covering. A layer of cGMP-positive (cGMP(+)) cells (up to
      10 cells deep) was found in the base. cGMP(+)/SU-ICs were also observed in the
      lateral wall. However, here, the cGMP(+) cells were confined to a layer of only 1
      2 cells immediately below the basal urothelial layer (basal cGMP(+)/SU-ICs).
      Below these cGMP(+)/SU-ICs lay cells that had a similar structure but that showed
      little cGMP accumulation (deep cGMP(-)/SU-ICs). Both basal and deep SU-ICs
      expressed the beta1 subunit of sGC and the cGMP-dependent protein kinase I
      (cGKI), suggesting that the deep SU-ICs can sense NO and signal via cGMP. By
      using BAY 41-2272, a sensor of endogenous NO production, NO-dependent cGMP
      synthesis was observed primarily in the basal SU-ICs. A third population of
      cGKI(+)/cGMP(-) cells was seen to lie immediately below the basal urothelial
      layer. These cells ("necklace" cells) were less numerous than SU-ICs and extended
      linking processes suggesting a network. The specific functions of these
      structures are not known but they may contribute to the emerging multiple roles
      of the urothelium associated with the generation of bladder sensation.

PMID- 16598499
TI  - Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal
      adenocarcinomas: lack of mutations in the BRAF and EGFR genes.
AB  - The vast majority of tumors of the pancreas are ductal adenocarcinomas. This
      cancer type has an extremely poor prognosis and in many Western countries, it
      represents the fifth leading cause of cancer-related death. Pancreatic ductal
      adenocarcinomas exhibit the highest incidence of activating KRAS (Ki-Ras)
      mutations observed in any human cancer. It was therefore of interest to examine
      how this pattern would relate to mutations in the BRAF and EGFR genes, which are
      involved in the same signaling pathway as KRAS. We screened a series of 43
      formalin-fixed, paraffin-embedded ductal adenocarcinomas of the pancreas. When
      DNA was extracted from whole tissue sections, KRAS codon 12 mutations were
      detected in 67% of the tumors. When cancerous ducts were isolated by laser
      assisted microdissection, 91% were positive for KRAS mutations. Although it did
      not reach statistical significance, there was a trend in our material that
      survival after diagnosis varied according to KRAS mutation subtype, GTT-positive
      patients having the best prognosis. No alterations in BRAF exons 11 and 15 or in
      EGFR exons 18-21 were detected in KRAS-positive or KRAS-negative cases. We
      therefore conclude that the BRAF and EGFR mutations commonly seen in a variety of
      human cancers are generally absent from pancreatic ductal adenocarcinomas.
      Apparently, these tumors depend on no more than one genetic hit in the EGFR-RAS
      RAF signaling pathway.

PMID- 16598502
TI  - Community effects following the deletion of a habitat-forming alga from rocky
      marine shores.
AB  - Habitat-forming species increase spatial complexity and alter local environmental
      conditions, often facilitating a diversified assemblage of plants and animals.
      Removal of dominant species, therefore, can potentially lead to pronounced
      changes in diversity and community structure through a series of negative and
      positive interactions involving several components of the community. Here we test
      community responses to the deletion of the dominant, canopy-forming alga
      Hormosira banksii from the mid-intertidal zone of wave-protected rocky shores in
      southern New Zealand. This species was removed in winter (July) from three 3x3-m
      areas at each of two platforms (Kaikoura and Moeraki) on the east coast of the
      South Island. Initially, 59 taxa occurred in stands, but there were only four
      algal species with greater than 5% cover and three mobile invertebrate species
      with more than five individuals per 0.25 m(2). By 6 months after Hormosira
      removal, most fucoid and coralline algae had burned off, and there were blooms of
      ephemeral algae in the removal plots, but almost no change within controls. After
      2 years, diversity declined by 44% relative to controls at Kaikoura and 36% at
      Moeraki, and the amount of bare space had increased by tenfold at Kaikoura and
      twofold at Moeraki. Few sessile or mobile invertebrates were present. Recruitment
      of Hormosira occurred after 14 months in the removal plots. At this time, a
      "press" disturbance was initiated into one half of each removal plot to test the
      effects of continued removal of Hormosira on diversity. Similar "end-points" of
      the control and "press" removal plots were not reached after 2 years, and even
      after Hormosira recruitment into the original "pulse" experiment there was little
      recovery of the community. In this mid-intertidal system with considerable
      thermal stress, and perhaps in others with few perennial species, diversity and
      community structure can critically depend on positive associations with a single
      dominant species.

PMID- 16598503
TI  - Breaking bad news: evaluation study on self-perceived competences and views of
      medical and nursing students taking part in a collaborative workshop.
AB  - GOALS OF THE WORK: To identify possible effects of an interprofessional breaking
      bad news course for medical and nursing students on perceived key communication
      skills and to elicit the views of participants on interprofessional aspects of
      breaking bad news. PARTICIPANTS AND METHODS: Medical and nursing students
      attending an optional course on breaking bad news received a structured
      questionnaire on self-perceived communication skills and views on
      interprofessional aspects at the beginning and end of the course. MAIN RESULTS:
      Forty-seven out of 54 students completed the evaluation questionnaires (response
      rate=87%). Medical students and nursing students rated their key communication
      skills after the course as significantly better compared with the beginning of
      the course. Medical students and nursing students disagreed with the statement
      that a course format for only one of the professional groups would have been more
      effective than the interprofessional course concept. CONCLUSIONS: Students valued
      the concept of the interprofessional course positively. The improvement of self
      perceived communication skills may be interpreted as a positive effect of the
      teaching session. Further research is necessary to develop strategies to
      implement a collaborative approach in breaking bad news in clinical practice.

PMID- 16598504
TI  - Biodegradation of phenanthrene, spatial distribution of bacterial populations and
      dioxygenase expression in the mycorrhizosphere of Lolium perenne inoculated with
      Glomus mosseae.
AB  - Interactions between the plant and its microbial communities in the rhizosphere
      control microbial polycyclic aromatic hydrocarbons (PAH) biodegradation
      processes. Arbuscular mycorrhizal (AM) fungi can influence plant survival and PAH
      degradation in polluted soil. This work was aimed at studying the contribution of
      the mycorrhizosphere to PAH biodegradation in the presence of ryegrass (Lolium
      perenne L., cv. Barclay) inoculated with Glomus mosseae (BEG 69) by taking into
      account the structure and activity of bacterial communities, PAH degrading
      culturable bacteria as a function of the distance from roots. Ryegrass was grown
      in compartmentalized systems designed to harvest successive sections of
      rhizosphere in lateral compartments polluted or not with phenanthrene (PHE).
      Colonization of roots by G. mosseae (BEG 69) modified the structure and density
      of bacterial populations in the mycorrhizosphere, compared to the rhizosphere of
      non-mycorrhizal plants. G. mosseae increased the density of culturable
      heterotrophic and PAH degrading bacteria beyond the immediate rhizosphere in the
      presence of PHE, and increased the density of PAH degraders in the absence of the
      pollutant. Biodegradation was not significantly increased in the
      mycorrhizosphere, compared to control non-mycorrhizal plants, where PHE
      biodegradation already reached 92% after 6 weeks. However, dioxygenase
      transcriptional activity was found to be higher in the immediate mycorrhizosphere
      in the presence of G. mosseae (BEG 69).

PMID- 16598505
TI  - Limited transfer of nitrogen between wood decomposing and ectomycorrhizal mycelia
      when studied in the field.
AB  - Transfer of (15)N between interacting mycelia of a wood-decomposing fungus
      (Hypholoma fasciculare) and an ectomycorrhizal fungus (Tomentellopsis submollis)
      was studied in a mature beech (Fagus sylvatica) forest. The amount of (15)N
      transferred from the wood decomposer to the ectomycorrhizal fungus was compared
      to the amount of (15)N released from the wood-decomposing mycelia into the soil
      solution as (15)N-NH(4). The study was performed in peat-filled plastic
      containers placed in forest soil in the field. The wood-decomposing mycelium was
      growing from an inoculated wood piece and the ectomycorrhizal mycelium from an
      introduced root from a mature tree. The containers were harvested after 41 weeks
      when physical contact between the two foraging mycelia was established. At
      harvest, (15)N content was analyzed in the peat (total N and (15)NH(4) (+)) and
      in the mycorrhizal roots. A limited amount of (15)N was transferred to the
      ectomycorrhizal fungus and this transfer could be explained by (15)NH(4) (+)
      released from the wood-decomposing fungus without involving any antagonistic
      interactions between the two mycelia. Using our approach, it was possible to
      study nutritional interactions between basidiomycete mycelia under field
      conditions and this and earlier studies suggest that the outcomes of such
      interactions are highly species-specific and depend on environmental conditions
      such as resource availability.

PMID- 16598507
TI  - Behavioural evidence of UV sensitivity in jumping spiders (Araneae: Salticidae).
AB  - Jumping spiders are known to possess ultraviolet (UV) receptors in the retinas of
      their large-principal eyes. The existence of UV visual cells, however, does not
      prove that jumping spiders can see into the UV part of spectrum (300-400 nm) or
      whether such an ability plays any role in salticid intra-specific interactions.
      In the study reported herein, we performed behavioural experiments to test
      whether a UV-reflecting jumping spider, Cosmophasis umbratica, is sensitive to UV
      wavelengths and whether UV cues are important in intra-specific communication.
      The absence of UV cues not only affected intra-specific behaviour by
      significantly reducing the frequency of agonistic displays, but also elicited
      unprecedented courtship displays in males towards their own mirror images and
      conspecific opponents. Furthermore, C. umbratica males were able to respond
      rapidly to changes in UV cues of conspecific mirror images by switching between
      agonistic and courtship displays. These findings clearly demonstrate that C.
      umbratica males are capable of seeing UV wavelengths and that UV cues are
      necessary and sufficient for this species to enable the agonistic displays.
      Hence, UV light may have an important role to play in intra-specific
      communication in jumping spiders.

PMID- 16598506
TI  - Study on three-dimensional kinematics and electromyography of ACL deficient knee
      participants wearing a functional knee brace during running.
AB  - This investigation examined the muscular activity and 3D knee joint kinematic
      changes of anterior cruciate ligament-deficient (ACLD) participants in the
      involved leg under bracing condition during running. Different adaptation
      strategies have been found between patients who can cope with the injury and
      patients who cannot. One of the expected changes can be the muscle activation
      characteristic of the injured knee during strenuous activity with and without a
      functional knee brace. Three-dimensional kinematic and electromyographical (EMG)
      data were collected from 11 participants for 10 consecutive gait cycles during
      running on a treadmill under both braced and unbraced conditions. Participants
      were administered the "Knee Outcome Survey Activities of Daily Living Scale" to
      distinguish functional and non-functional candidates. No significant differences
      on 3D kinematics and EMG data were noted between functional and non-functional
      participants, thus data analysis focused on comparisons of bracing conditions for
      one combined group. Bracing significantly reduced total range of motion in the
      frontal and transverse planes (P<0.05). Muscle activity at heel-strike showed a
      consistent trend to increase for the hamstrings and decrease for the quadriceps
      under the braced condition when compared to the unbraced condition. Our findings
      indicate that bracing the ACLD knee alters the kinematics of the injured leg
      while running. Tendencies toward reductions in quadriceps and increases in
      hamstrings activity at heel-strike indicate that bracing might have resulted in
      added stability of the injured knee. The adaptations to bracing found in this
      preliminary study further support the potential mechanical and proprioceptive
      contributions of the functional knee brace to protect the ACLD knee.

PMID- 16598508
TI  - Subclavian venipuncture following ipsilateral extrapleural dissection is
      hazardous.
AB  - Subclavian artery puncture is an infrequent complication of subclavian vein
      cannulation. In spite of the limited ability to apply direct pressure to the
      bleeding vessel, significant hematoma or exsanguinating bleeding rarely occurs.
      This study was a retrospective chart review of a neonate who underwent
      extrapleural repair of a tracheo-esophageal fistula and sustained significant
      blood loss following an accidental ipsilateral subclavian artery puncture. This
      case highlights the importance of an intact apical pleura in controlling bleeding
      from the subclavian vessels. Thus, ipsilateral percutaneous subclavian
      venipuncture should be avoided in patients in whom the apical pleura is not
      intact.

PMID- 16598509
TI  - Transpubic radical prostatectomy: a novel approach for rhabdomyosarcoma of the
      prostate in children.
AB  - Rhabdomyosarcoma is the most common soft tissue sarcoma, representing 10-15% of
      all malignant solid tumours in children and can occur in any site. The prognosis
      for rhabdomyosarcoma of the prostate has improved significantly in the last few
      decades. The management involves a combination of chemotherapy, radiotherapy and
      surgery. Several approaches to resect the prostate in adults have been described.
      These include radical retropubic, transperineal, posterior sagittal as well as
      the transpubic approach. In the child, the transpubic approach allows direct
      access to the prostate and proximal urethra whilst obviating problems noted in
      adults. We describe this approach to the prostate in a 3-year-old boy.

PMID- 16598510
TI  - Cirsoid aneurysms of the scalp.
AB  - This study reviewed the surgical management of cirsoid aneurysms of the scalp,
      which are rarely encountered in the neurosurgical practice, and compares the
      results with embolization. 21 patients with cirsoid aneurysm underwent surgery.
      There were 1 female and 20 male patients. Trauma was present in four patients.
      Selective internal and external carotid artery angiograms and cranial magnetic
      resonance imaging studies were performed on all patients. All angiograms were
      staged according to published procedures. There were 15 (71.4%) Stage 1a, 4
      (19.1%) Stage 1b, and 2 (9.5%) Stage 3 patients. Total excision of the lesion was
      achieved in 19 patients (90.5%). We operated on only one patient for a second
      time, because of a residual lesion, and we resected the lesion totally. Only two
      patients developed necrosis of the scalp (button hole). Both scalp necroses were
      on the frontal area. Other patients all had good cosmetic results. Surgical
      resection of cirsoid aneurysms seems to be the most effective treatment with good
      results. There may be a tendency for the occurrence of necrosis on the frontal
      area. Staging of the scalp aneurysms has no effect on surgical outcome.

PMID- 16598511
TI  - Very high ethanol productivity in an innovative continuous two-stage bioreactor
      with cell recycle.
AB  - The performance of an innovative two-stage continuous bioreactor with cell
      recycle-potentially capable of giving very high ethanol productivity-was
      investigated. The first stage was dedicated to cell growth, whereas the second
      stage was dedicated to ethanol production. A high cell density was obtained by an
      ultrafiltration module coupled to the outlet of the second reactor. A recycle
      loop from the second stage to the first one was tested to improve cell viability
      and activity. Cultivations of Saccharomyces cerevisiae in mineral medium on
      glucose were performed at 30 degrees Celsius and pH 4. At steady state, total
      biomass concentrations of 59 and 157 gDCW l(-1) and ethanol concentrations of 31
      and 65 g l(-1) were obtained in the first and second stage, respectively. The
      residual glucose concentration was 73 g l(-1) in the first stage and close to
      zero in the second stage. The present study shows that a very high ethanol
      productivity (up to 41 g l(-1) h(-1)) can indeed be obtained with complete
      conversion of the glucose and with a high ethanol titre (8.3 degrees GL) in the
      two-stage system.

PMID- 16598512
TI  - ACE inhibition in secondary prevention: are the results controversial?
AB  - Results from the HOPE and EUROPA trials showed that ACE inhibitors lower
      cardiovascular mortality of patients with atherosclerosis and preserved left
      ventricular function. However, despite apparently adequate study design, the
      recently conducted PEACE trial detected no benefit of an additional ACE inhibitor
      treatment in patients with coronary artery disease and no heart failure with
      respect to cardiovascular risk reduction. One of the main reasons for this
      discrepancy might be the lower cardiovascular baseline risk of the PEACE study
      population, which was more intensively treated with lipid lowering drugs and
      myocardial revascularization prior to enrollment than patients in HOPE or EUROPA.
      Another reason for the negative results of PEACE might be substance-specific
      differences between individual ACE inhibitors (trandolapril in PEACE, ramipril in
      HOPE, and perindopril in EUROPA) in their clinical efficacy to reduce
      cardiovascular end-points. The PEACE trial did not achieve the originally
      projected sample size and the addition of a soft end-point of revascularization
      has not been helpful. While the results from the PEACE trial suggest that low
      risk patients with coronary artery disease and with preserved left ventricular
      function who receive intensive standard therapy including lipid lowering and
      coronary revascularization may not benefit from additional ACE inhibition
      therapy, this conclusion should be made with caution. A number of reasons, other
      than drug treatment efficacy, may explain the neutral results in the PEACE trial.
      Further studies are needed to try to resolve this issue. In the meantime, the
      overwhelming data still support the use of ACE inhibitors in patients with
      coronary artery disease with preserved left ventricular function.

PMID- 16598513
TI  - An unusual cause of dyspnoea and pulmonary hypertension in a patient with a
      symptom history of 20 years--"Just do it again".

PMID- 16598514
TI  - Native infective endocarditis: which determinants of outcome remain after
      surgical treatment?
AB  - Surgical therapy of native infective endocarditis is still considered as a
      particular challenge, due to remaining morbidity and mortality up to 20%. Further
      risk analysis and characterization of clinical features is of great importance
      for further improvement of surgical results. The aim of this retrospective study
      was a risk analysis concerning clinical features of the pre-, intra- and
      postoperative period. Between 02/1997 and 12/2003, 165 patients (130 male, 35
      female, age 55.5 +/- 13.8 years) were referred for surgical therapy of infective
      endocarditis at our institution. Preoperative, intraoperative and postoperative
      features were evaluated for their influence on the early postoperative course and
      the mid-term follow-up. In the majority of patients (pts) the aortic valve was
      infected (n = 83, 50.3% of pts), followed by mitral valve (n = 33; 20.0%),
      tricuspid valve (n = 10, 6.0%) and pulmonary valve (n = 2; 1.2%). Double valve
      affection was recorded in 37 pts (22.4%). Streptococci (n = 66, 40.0%) and
      staphylococci (n = 66, 40.0%) were the most common pathogens. The overall
      hospital mortality rate was 10.9% (n = 18), during follow-up (mean follow-up 3.3
      +/- 2.5 years) a further 20 pts (12.1%) died.Main predictors for hospital
      mortality in multivariate analysis were older age (p = 0.01), prolonged ICU stay,
      prolonged intubation (p = 0.03; p = 0.02) and the continuous postoperative need
      of alpha-catecholamine medication (p < 0.01). Significant predictors of overall
      mortality were older age (> 70 years) and diabetes (p = 0.03; p = 0.03).
      Reinfection occurred in 6.1% of patients (n = 10). Actuarial freedom from
      recurrent infection was 97% at 1 year and 93.9% at 5 years. Surgical therapy of
      infective endocarditis is associated with good clinical results in the early and
      mid-term follow-up. Predictors of outcome particular include preoperative risk
      constellation or comorbidity (age, diabetes) and variables of the immediate
      postoperative course.

PMID- 16598515
TI  - High prevalence of undiagnosed impaired glucose regulation and diabetes mellitus
      in patients scheduled for an elective coronary angiography.
AB  - BACKGROUND: Impaired glucose regulation (IGR) and diabetes mellitus (DM) are
      amongst the main risk factors for developing coronary heart disease (CHD). The
      aim of this study was to investigate previously unknown glucose metabolism
      disorder in patients scheduled for an elective coronary angiography. METHODS: A
      total of 141 patients scheduled for coronary angiography without signs of acute
      myocardial ischemia or previous history of a glucose metabolism disorder were
      prospectively included in the study. An oral glucose tolerance test (OGTT) was
      performed in each patient. RESULTS: IGR was diagnosed in 40.4% (95% confidence
      interval 32.3-49.0) and undetected DM in 22.7% (16.1-30.5) of patients undergoing
      an elective coronary angiography. Depending on the severity of CHD, the
      percentage of IGR and DM increased up to 45.3% (34.6-56.5) and 26.7% (17.8-37.4)
      in the subgroup with the need of percutaneous angioplasty, while the
      corresponding proportions in the group without CHD were 30.3% (15.6-48.7) and
      12.1% (3.4-28.2). The percentage of undiagnosed DM increased with the number of
      epicardial vessels involved. Using the recommended fasting plasma glucose value
      of > or = 126 mg/dl for the diagnosis of DM, we would have missed 71.9% of the
      patients with undiagnosed DM. If all patients with a fasting plasma glucose of >
      or = 90 mg/dl had been subjected to OGTT, 93.8% of DM would have been identified.
      CONCLUSIONS: Prevalences of DM and IGR are higher than expected in patients with
      CHD. An OGTT should be considered for all patients with a fasting plasma glucose
      > or = 90 mg/dl undergoing a coronary angiography.

PMID- 16598516
TI  - Self-fabricated fenestrated Amplatzer occluders for transcatheter closure of
      atrial septal defect in patients with left ventricular restriction: midterm
      results.
AB  - To avoid left ventricular failure after transcatheter closure of atrial septal
      defects in elderly patients with restrictive left ventricular physiology, partial
      occlusion by fenestrated devices may be an option. If complete defect closure is
      not possible in these patients, significant reduction of left to right shunting
      usually results in clinical benefit. We report two patients in whom deterioration
      of left ventricular function could be avoided by implantation of self-fabricated
      fenestrated Amplatzer Septal Occluders (ASO) in patients with ongoing restrictive
      left ventricular physiology. We describe technical preparation of the standard
      occluder, the specific implantation technique, and the initial and the
      intermediate term results up to 24 months.

PMID- 16598517
TI  - Coronary reoperation with and without cardiopulmonary bypass.
AB  - Redo coronary artery bypass grafting (CABG) is still associated with increased
      morbidity and mortality compared to primary operation. Myocardial protection is
      one of the key issues in redo on pump CABG and is still a matter of debate. Off
      pump redo CABG seems to be an attractive alternative as native coronary blood
      flow remains and cross clamping of the aorta is avoided. The aim of this
      retrospective study was to compare the outcome of redo CABG with and without CPB.
      From 1/1998 to 5/2004 redo CABG was performed in 195 patients (pts): 162 male
      (83.1%) and 33 female (16.9%) pts, age 66 +/- 9 years. In 160 pts, CPB with
      isolated antegrade myocardial protection was used for redo CABG. Off pump redo
      CABG was performed in 35 pts (30 male (85.7%) and 5 female (14.3%), age 67 +/- 8
      years). Perioperative overall mortality rate was 3.6% (n = 7) and comparable in
      both groups (on pump 3.8% versus off pump 2.9%; p = 0.90), as well as
      perioperative myocardial infarction, intraaortic balloon pump implantation rate
      and secondary morbidity. Complete revascularization was achieved in 139 pts
      (86.9%) after on pump CABG and in 17 pts (48.6%) of the off pump group (p <
      0.01). The average number of grafts was significantly higher in the on pump group
      (2.8 +/- 0.78 versus 1.6 +/- 0.6; p = 0.04).Furthermore, 20 pts (12.5%) in the on
      pump group died during follow-up (50 +/- 16 months). Five pts (25.0%) died due to
      cardiac reasons. In the off pump group 3 pts (8.6%) died during follow-up (44 +/-
      13 months), noncardiac related. Overall survival was 83.8% in the on pump group
      and 88.6% in the off pump group (p = 0.92). On pump redo CABG and off pump redo
      CABG can be safely performed with low mortality and morbidity. Off pump redo CABG
      might be limited due to incomplete revascularization.

PMID- 16598518
TI  - After myocardial infarction carvedilol improves insulin resistance compared to
      metoprolol.
AB  - PRINCIPLES: Both carvedilol and metoprolol have cardioprotective effects and
      decrease infarct size in myocardium. We compared effects of carvedilol and
      metoprolol on insulin resistance and serum lipid levels after myocardial
      infarction. METHODS: Fifty-nine patients aged between 30 and 70 and BMI = 25-30
      kg/m2, who were diagnosed with myocardial infarction with ST segment elevation,
      were considered to be eligible for the study. Patients were randomly allocated to
      two different therapy protocols. Metoprolol 100 mg bid or carvedilol 25 mg bid
      was added to their standardized therapy regimen. Baseline to week 4 and 12,
      fasting blood glucose, serum lipid profile, BMI, C-peptide, insulin and
      homeostasis model assessment of insulin resistance (HOMA-IR) were measured.
      RESULTS: After 12 weeks of metoprolol therapy HOMA-IR, insulin and C-peptide
      levels were significantly higher (p < 0.05 for all) and total cholesterol and
      triglyceride levels decreased significantly (p < 0.05 for all) compared to
      baseline. After 12 weeks of carvedilol therapy HOMA-IR, insulin and C-peptide (p
      < 0.05 for all), total cholesterol and triglyceride (p = 0.001 for all) decreased
      significantly compared to baseline. Carvedilol provided more decrease in total
      cholesterol and LDL levels than metoprolol (p = 0.043 and p = 0.021,
      respectively). CONCLUSIONS: In patients after myocardial infarction, carvedilol
      added to background therapy improved insulin resistance and lipid profile.

PMID- 16598519
TI  - Feasibility of 2-deoxy-2-[18F]fluoro-D-glucose- A85380-PET for imaging of human
      cardiac nicotinic acetylcholine receptors in vivo.
AB  - Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control
      of cardiac function. Aim of this study was the assessment of cardiac nicotinic
      acetylcholine receptor distribution with a novel (alpha4beta2) nicotinic
      acetylcholine receptor PET ligand (2-deoxy-2- [18F]fluoro-D-glucose-A85380) in
      humans. Five healthy volunteers without cardiac disease and six patients with
      either Parkinson's disease or multiple system atrophy without additional overt
      cardiac disease were evaluated with 2-deoxy-2-[18F]fluoro-D-glucose-A85380 PET
      imaging to assess the cardiac parasympathetic innervation and the putative impact
      of both disorders. 2-deoxy-2- [18F]fluoro-D-glucose-A85380 whole body PET-scans
      were performed on a Siemens PET/CT biograph(TM) 75.4 min +/- 6.7 after i.v.
      injection of 371.2 +/- 58.1 MBq. Average count rate density of left ventricle
      ROI's and a standard ROI in the right lung were measured within three consecutive
      slices of 10.0 mm thickness. Heart-to-lung ratios were calculated in each
      volunteer and patient. Tracer uptake in the left ventricle could be measured in
      all of the five volunteers and the six patients. Heart-to-lung ratios in the
      volunteer group were not different from patients suffering from Parkinson's
      disease or MSA (3.2 +/- 0.5 vs 3.2 +/- 0.8 and 2.96+/-0.7, mean +/- SD),
      respectively. Human cardiac nicotinic acetylcholine receptors can be visualized
      and measured by 2-deoxy-2- [18F]fluoro-D-glucose-A85380 PET scans both in cardiac
      healthy subjects and patients suffering from Parkinson's disease or multiple
      system atrophy. The heart- as well as the lung-tracer uptake was almost constant
      throughout all subjects leading to a good target-to-background ratio. These first
      results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine
      receptors.

PMID- 16598520
TI  - Hypoplastic left heart syndrome with intact atrial septum--attempt of an
      interventional palliation by ductal and interatrial stent implantation.
AB  - In patients with hypoplastic left heart syndrome (HLHS) and intact atrial septum,
      the blood entering the left atrium cannot egress. Emergency treatment
      interventionally or surgically is mandatory immediately after birth. We describe
      a patient with HLHS and intact atrial septum who underwent successful transvenous
      atrial septostomy immediately after birth. When the interatrial communication
      became restrictive, stent implantation into the arterial duct and into the atrial
      septum was performed on the 7th day of life. Despite good hemodymanic response,
      the lung damage was severe and persistent, rendering staged surgical correction
      impossible. The child died on the 23rd day of life. Autopsy showed patent and
      correct placed stents in the duct and the atrial septum. There was severe
      dilatation of pulmonary lymphatic and venous vessels, suggestive of long-standing
      pulmonary venous hypertension. In conclusion, this form of HLHS has a poor
      prognosis despite early and aggressive interventional treatment.

PMID- 16598521
TI  - Coronary artery spasm of the native right coronary artery during off-pump
      coronary surgery of the left coronary artery system.
AB  - Native coronary artery spasm is a very rare complication during off-pump coronary
      artery bypass grafting. We report the case of a 74-year-old man who experienced
      angiographically documentated right coronary artery spasm while undergoing off
      pump coronary artery bypass grafting on the diseased left coronary system.
      Despite two episodes of ventricular fibrillation and persistent ST segment
      elevation of the posterior wall, the off-pump procedure was successfully
      completed by grafting the left internal thoracic artery to the left anterior
      descending artery and a saphenous vein graft to the Ramus intermedius. The
      immediate postoperatively performed coronary angiography demonstrated patent
      anastomoses and two areas of significant spasticity within the course of the
      right coronary artery. Intracoronary nitroglycerin infusion into the ostium of
      the right coronary artery resolved the spasms of this nondiseased vessel as well
      as the associated ST segment elevations.

PMID- 16598522
TI  - Single coronary artery with anomalous origin from the right sinus Valsalva.
AB  - A single coronary artery is a rare congenital anomaly with an incidence of 0.02
      0.04%. We report on a 65-year-old male presenting with atypical chest pain and a
      history of hypertension and hypercholesterinemia, having diagnosed a very rare
      variant of a single coronary artery arising from the right sinus of Valsalva
      continuing as circumflex coronary artery (LCX) and thereafter as left anterior
      descending artery (LAD). Because the patient was asymptomatic on antiischemic
      medication and had a proposed relative benign course, we recommended medical
      treatment without coronary artery bypass surgery, and the patient has been in
      fine condition up to now (11 months after angiography).

PMID- 16598523
TI  - Combined aspirin and clopidogrel resistance associated with recurrent coronary
      stent thrombosis.
AB  - We report about a 72-year-old woman who was admitted to our hospital because of
      an acute ST-elevation myocardial infarction (STEMI). At admission, she received a
      loading dose of 300 mg Clopidogrel and 500 mg aspirin (ASA) prior to angioplasty
      with stenting of a 90% diameter stenosis of the proximal right coronary artery.
      After intervention, 75 mg Clopidogrel and 300 mg ASA OD were continued. Three
      days later, she developed a recurrent acute STEMI due to stent thrombosis and a
      second stent implantation was performed. The dose of Clopidogrel and ASA remained
      unchanged. Three days later, the patient suffered a third STEMI due to a restent
      thrombosis and additional stent implantation was performed. The dose of
      Clopidogrel and ASA was increased to 75 mg BD and 500 mg OD. Platelet function
      analysis and aggregation studies demonstrated dose-independent ASA resistance.
      ADP-induced aggregation showed a short-term platelet inhibition with subsequent
      rapid normalisation, thus suggesting Clopidogrel resistance. Therefore, the
      treatment was changed to coumadin and ASA 100 mg OD. Since then, the patient has
      been clinically stabile. Our case indicates for the first time the existence of a
      subgroup of patients with combined Clopidogrel and ASA resistance. We conclude
      that identification of these patients is required and alternative therapeutic
      options have to be considered.

PMID- 16598524
TI  - Ruptured sinus of Valsalva aneurysm in two patients with subarterial ventricular
      septal defect.
AB  - Rupture of a sinus of Valsalva aneurysm (SVA) is a rare, but life-threatening,
      event and requires immediate recognition and intervention. We present two
      previously healthy and physically active patients who were 12 and 33 years of age
      when rupture of a right coronary SVA into the right ventricle occurred. A
      subarterial ventricular septal defect (VSD) was detectable in both patients.
      Cardiac surgery involved VSD closure as well as reconstruction of the aortic
      valve. Considering complications of subarterial VSD, such as aortic cusp
      prolapse, aortic insufficiency or SVA, we suggest close follow-up and surgical
      closure of the VSD in case of any aortic valve deformity.

PMID- 16598525
TI  - Wolff-Parkinson-White syndrome associated with persistent left superior vena
      cava.

PMID- 16598527
TI  - Atrial fibrillation - patients at high risk for cerebral embolism.
AB  - OBJECTIVE: Patients with atrial fibrillation (AF) have a risk of cerebral
      embolism. Echocardiographic parameters elevate this risk significantly. However,
      there is little knowledge about the long-term fate and the rate of clinically
      silent cerebral embolism under continued oral anticoagulation. The aims of our
      study were to assess prognosis of patients with AF and determine a high risk
      group with an increased risk of cerebral embolism under oral anticoagulation.
      METHODS: Consecutive patients with persistent or permanent AF and left atrial
      (LA) thrombi, dense spontaneous echo contrast (SEC) and/or reduced LA appendage
      peak emptying velocities (LAAv) were included in the study (N = 128). Patients
      with AF and without echocardiographic risk factors (N = 114) served as controls.
      All patients were examined with transesophageal echocardiography, cranial
      magnetic resonance imaging and clinically during a period of three years.
      RESULTS: During the three-year follow-up period 6 (5%) of the high risk patients
      had cerebral embolism with neurological deficits. 4 (3%) patients died due to
      embolic events and 17 (13%) patients had silent embolism as documented on MRI. In
      the control group 8 (7%) patients had embolic events (n = 1 clinically apparent
      and n = 7 silent embolism) documented on MRI, one was clinically apparent. Study
      patients with an event had more commonly previous thromboembolism (p < 0.0001).
      CONCLUSIONS: Patients with peristent or permanent AF and LA thrombi, dense SEC or
      reduced LAAv have an explicitly increased risk of cerebral embolism (21%) despite
      oral anticoagulation. Previous thromboembolic event is another important
      predictor for an event.

PMID- 16598528
TI  - Implementation of evidence-based therapy in patients with systolic heart failure
      from 1998-2000.
AB  - BACKGROUND: In recent years, the incidence of systolic heart failure has
      increased. Besides a complete revascularization, guideline-based medication
      represents the most effective therapeutic approach. AIM: Analysis of adherence of
      guideline-recommended and actual medication during inpatient cardiac
      rehabilitation as well as under subsequent outpatient conditions. METHODS: From
      01/1998 to 12/ 2000, 1346 consecutive patients (64 +/- 10 years, 73% male, LVEF
      36.3 +/- 8%, 88% ischemic, 6.7% valvular cardiomyopathy, 5.3% other causes, 11.8%
      atrial fibrillation) were included in a singlecenter prospective register.
      Medication was recorded at discharge and after the follow-up period of 731 +/-
      215 days. Trends in prescription rates were analyzed based on nonparametric
      correlations (Spearman's-Rho). Changes in medication from in- to outpatient
      settings were analyzed using exact McNemar test. RESULTS: At discharge 75.3%
      (67.9%/68.9%/ 86.6% in 1998/1999/2000, p <0.001) of the patients were treated as
      recommended. This rate dropped to 68.3% at followup (p <0.0001). Mortality within
      the follow-up period was low (12.6%). CONCLUSION: It could be shown that from
      1998 to 2000 inpatient guideline conformity was implementable adequately.
      Outpatient conformity was significantly lower. Although a high proportion of
      correctly prescribed CHF medication could be demonstrated, a further effort to
      improve guideline adherence in the management of heart failure patients is
      desirable.

PMID- 16598526
TI  - Gender differences in the metabolic syndrome and their role for cardiovascular
      disease.
AB  - Women live longer than men and develop cardiovascular disease (CVD) at an older
      age. The metabolic syndrome represents a major risk factor for the development of
      CVD, and gender differences in this syndrome may contribute to gender differences
      in CVD. In recent years, the metabolic syndrome has been more prevalent in men
      than in women. Prevalence is increasing and this increase has been steeper in
      women, particularly in young women, during the last decade. The contributions of
      the different components of the metabolic syndrome differ between genders and in
      different countries. In a recent survey in Germany, 40% of the adult population
      had been diagnosed with disturbed glucose tolerance or type 2 diabetes.
      Undiagnosed diabetes was more frequent in men than in women, and risk factors for
      undiagnosed diabetes differed between the sexes. Worldwide, in individuals with
      impaired glucose tolerance, impaired fasting glucose was observed more frequently
      in men, whereas impaired glucose tolerance occurred relatively more often in
      women. Lipid accumulation patterns differ between women and men. Premenopausal
      women more frequently develop peripheral obesity with subcutaneous fat
      accumulation, whereas men and postmenopausal women are more prone to central or
      android obesity. In particular, android obesity is associated with increased
      cardiovascular mortality and the development of type 2 diabetes. Visceral
      adipocytes differ from peripheral adipocytes in their lipolytic activity and
      their response to insulin, adrenergic and angiotensin stimulation and sex
      hormones. Visceral fat is a major source of circulating free fatty acids and
      cytokines, which are directly delivered via the portal vein to the liver inducing
      insulin resistance and an atherogenic lipid profile. Inflammation increases
      cardiovascular risk particularly in women. A relatively greater increase in
      cardiovascular risk by the appearance of diabetes in women has been reported in
      many studies.Thus, the presently available data suggest that the pathophysiology
      of the metabolic syndrome and its contribution to the relative risk of
      cardiovascular events and heart failure show gender differences, which might be
      of potential relevance for prevention, diagnostics, and therapy of the syndrome.

PMID- 16598529
TI  - A hybrid approach for quantification of aortic valve stenosis using cardiac
      magnetic resonance imaging and echocardiography: comparison to right heart
      catheterization and standard echocardiography.
AB  - We replaced Doppler-derived stroke volume in the continuity equation (method A)
      by either right heart catheterization-derived stroke volume (method B) or
      cardiovascular magnetic resonance-derived stroke volume (method C) to calculate
      aortic valve area in 20 consecutive patients with moderate or severe aortic
      stenosis. Comparison of both hybrid methods (methods B and C) by Bland-Altman
      analysis showed a mean difference near zero, a spread within two standard
      deviations and very similar limits of agreement. More importantly, all patients
      were classified into the same category of severity by both methods.

PMID- 16598530
TI  - Bundle branch reentrant tachycardia in a patient with a calcified bicuspid aortic
      valve and normal ventricular function.
AB  - We report the case of a bundle branch reentrant tachycardia (BBRT) in a 40
      yearold patient with a calcified bicuspid aortic valve and normal left
      ventricular function. The ventricular tachycardia was eliminated by successful
      radiofrequency ablation of the right bundle branch. As the aortic valve annulus
      is in close proximity to the specialized conduction system, premature
      degeneration of a bicuspid aortic valve may involve the bundle of His and the
      proximal bundle branches by invading calcifications. We speculate that
      calcifications invading the proximal bundle branches from the bicuspid aortic
      valve may have created the substrate for the BBRT in this patient.

PMID- 16598531
TI  - Interventional embolization of a giant pulmonary arteriovenous malformation with
      right-left-shunt associated with hereditary hemorrhagic telangiectasia.
AB  - A 46-year old woman experienced an episode of arterial desaturation despite
      administration of 100% oxygen during anesthetization for an elective laparoscopy.
      Further evaluation revealed a giant pulmonary arteriovenous malformation (PAVM)
      with right-left shunt associated with previously undiagnosed hereditary
      hemorrhagic telangiectasia (HHT, Morbus Osler- Weber-Rendu). The PAVM was treated
      interventionally with an Amplatzer duct occluder. Transcatheter embolization of
      the PAVM was well tolerated with symptomatic and hemodynamic improvement. CT scan
      after six months demonstrated correct position of the duct occluder in the left
      pulmonary artery with nearly complete occlusion of the feeding vessel.PAVMs are
      rare direct communications between pulmonary arteries and veins, associated with
      HHT in the majority of cases and often presenting with dyspnea or major
      neurological complications due to paradoxic embolism. In this case report, we
      present a rational and stepwise diagnostic workup for this rare medical condition
      and show that transcatheter embolization is an appropriate treatment for larger
      malformations.

PMID- 16598532
TI  - Stress cardiomyopathy mimicking acute coronary syndrome: case presentation and
      review of the literature.
AB  - Stress cardiomyopathy is a novel clinical syndrome affecting predominantly
      elderly female patients. It is characterized by severe reversible left
      ventricular dysfunction demonstrating a peculiar pattern of extensive apical wall
      motion abnormality known as "apical ballooning". The syndrome is typically
      precipitated by acute severe emotional, psychological or physical stress. It
      mimics acute coronary syndrome exhibiting typical clinical and
      electrocardiographic features of acute myocardial infarction. At angiography,
      however, significant coronary artery disease is invariably excluded. In the acute
      phase, the syndrome may be complicated by cardiogenic shock or ventricular
      fibrillation. Clinical data indicate that the disease is associated with an
      extensive increase of endogenous cathecholamine levels which may exhibit a direct
      toxic effect on the myocytes causing non-ischemic myocardial "stunning". This
      mechanism may have important implications for the management of patients in the
      acute phase of the disease. The prognosis of stress cardiomyopathy, however,
      seems favorable with recovery of global and regional myocardial function within a
      few weeks in the vast majority of patients. Yet, long-term outcome data in larger
      patient populations are lacking. We report the case of a female patient
      presenting with stress cardiomyopathy and review the current knowledge of the
      disease.

PMID- 16598534
TI  - Radiofrequency catheter septal ablation for HOCM in childhood by M. Emmel, N.
      Sreeram, J. V. deGiovanni, K. Brockmeier; Z Kardiol 94:699-703 (2005).

PMID- 16598533
TI  - Reversible cerebral hyperperfusion syndrome after stenting of the carotid artery 
      two case reports.
AB  - Hyperperfusion syndrome can complicate carotid revascularization, be it
      endarterectomy or carotid artery stenting (CAS). Although extensive effort has
      been devoted to reducing the incidence of ischemic stroke complicating CAS,
      little is known about the incidence, etiology, and prevention strategies for
      hyperperfusion following CAS. We report two cases (female patients 72 and 81
      years) presenting severe internal carotid stenosis (> 90%), who underwent
      presurgical and therapeutic intervention with CAS. Both patients developed
      hyperperfusion symptoms at 2 hours and at 30 minutes, respectively, following
      stenting, in both cases unilateral hyperperfusion was CCT confirmed. Case 1 was
      presenting with acute edema of the right hemisphere, case 2 with distended focal
      edema (left fronto-temporoparietally). Hyperperfusion syndrome and neurological
      symptoms retroceded in both cases (conservative therapy) and both patients
      returned to full activity (case 2 within 48 hours).

PMID- 16598536
TI  - [The importance of rehabilitation with cardiovascular diabetic patients after
      surgical interventions].
AB  - Patients with diabetes nowadays are not directly endangered by dysglycemia, but
      they suffer vascular complications. The diabetic patient with existing
      cardiovascular (CV) disease has a particularly high risk for further CV
      complications and, therefore, requires specific attention. These patients need an
      intense and multimodal therapeutic approach which includes a strong
      interdisciplinary cooperation between the cardiologist and the diabetologist.
      Cardiac rehabilitation can effectively improve prognosis of CV patients with
      numbers needed to treat (NNT) comparable to standard pharmacological treatment.
      In diabetics, after coronary surgery, metabolism frequently and markedly
      deteriorates, and this requires strict metabolic monitoring and close cooperation
      between the diabetes team and the other professionals (cardiologist, nurses,
      physiotherapists, psychologists . . .) to reduce complications arising from
      hyperglycemia and also hypoglycemia and to improve the CV risk factors by
      lifestyle changes. Frequently, diabetes is only diagnosed during the hospital
      stay for CV complication; therefore, in these patients, specific attention is
      required for teaching and inauguration of therapy. Due to the high risk of these
      patients and the need of qualified metabolic co-treatment, following CV surgery,
      diabetic patients should be treated preferentially in rehabilitation centres
      specialised in both cardiac and metabolic care. Recent studies indicate that a
      multimodal and aggressive approach in CV diabetic patients can markedly improve
      their prognosis.

PMID- 16598535
TI  - [Current concepts of diabetic atherogenesis].
AB  - Morbidity and mortality in patients with diabetes is mainly driven by its
      vascular manifestations. The underlying pathophysiology of diabetes is centrally
      linked to increased generation of reactive oxygen species, namely superoxide and
      hydrogen peroxide. Superoxide, generated upon uncoupling of the mitochondrial
      respiratory chain, oxidizes endothelial-derived nitric oxide and thus impairs
      endothelial function. Superoxide-derived hydrogen peroxide is the principal
      substrate for leukocyte-derived peroxidases, in particular myeloperoxidase, which
      associates with endothelial cells and has been shown to catalytically oxidize
      nitric oxide in vivo. Superoxide also promotes synthesis of advanced glycation
      endproducts, which also exert potent proatherogenic properties. Moreover,
      superoxide and hydrogen peroxide activate the redox-sensitive transcription
      factors NF-kappaB and thus mediates expression of proinflammatory proteins like
      adhesion molecules. Herein some the most recent discoveries in the
      pathophysiology of diabetic vasculopathy are reviewed.

PMID- 16598537
TI  - [Long-standing therapy of the metabolic syndrome in diabetics after coronary
      artery bypass surgery].
AB  - Patients with type 2 diabetes often also exhibit additional features of the
      metabolic syndrome. These include specifically central obesity triggering
      development and maintenance of diabetes together with arterial hypertension,
      hypertriglyceridemia and low levels of high-density lipoprotein cholesterol.
      Chronic therapy of the metabolic syndrome in diabetics after coronary bypass
      surgery focuses on changes in lifestyle, i.e., cessation of smoking, changes in
      nutrition and increase in physical activity. Nutrition aims at fat reduction and
      modification to reduce saturated fatty acids, to allow mono- and polyunsaturated
      fatty acids instead, and moderate alcohol consumption. High fiber and complex
      carbohydrate diet complete the recommendations. Nutrition therapy connected to
      increases in physical activity are aimed at reducing weight in overweight and
      obese subjects, which should reduce their body weight by 5 to 10% within about 6
      months. Normal weight subjects benefit from increases in physical activity by
      lipid and glucose regulation as well as by reduction in mortality.Diabetes
      specific therapy aims at normoglycemia including postprandial blood glucose
      levels, reduces blood pressure supported by ACE inhibitors and aims at weight
      reduction. Reduction of LDL-cholesterol is the first line therapy, also
      diminishing small-dense LDL particles. Decreasing triglycerides and increasing
      HDL-cholesterol are further lipid-regulating aims. Specifically diabetics after
      coronary bypass surgery need LDL-cholesterol levels below 70 mg/d (1.8 mmol/L)
      and triglycerides below 150 mg/dL (1.7 mmol/L). In addition, in males HDL
      cholesterol should be at least above 40 mg/dl (1 mmol/L), in females above 50
      mg/dL (1.3 mmol/L).

PMID- 16598538
TI  - Effect of an exercise training program on endothelial dysfunction in diabetic and
      non-diabetic patients with severe chronic heart failure.
AB  - BACKGROUND: Endothelial dysfunction is found both in patients with chronic heart
      failure and in patients with insulin-treated type 2 diabetes mellitus. This
      endothelial dysfunction leads to a significant reduction in endothelium-derived
      vasodilation. Physical exercise can have a positive effect on endothelial
      dysfunction in patients with coronary artery disease, chronic heart failure and
      diabetes mellitus. It is not clear, however, whether an exercise program
      influences endothelial function in diabetics with chronic heart failure. Our
      study was thus aimed at investigating whether a special exercise program would
      affect endothelial function. Comparisons were made with insulin-treated type 2
      diabetics and with non-diabetics suffering from chronic heart failure. METHODS:
      42 patients with severe chronic heart failure (LVEF < or = 30%), insulin
      dependent diabetics (n=20, mean age 67+/-6 yrs, 16 male, 4 female), non-diabetics
      (n=22, mean age 68+/-10 yrs, 20 male, 2 female) participated in a 4-week exercise
      program consisting of ergometer and special muscle strength training. Before (T1)
      and at the end (T2) of the training program endothelium-dependent and endothelium
      independent vasodilatory capacity were assessed by brachial artery diameter
      measurement. RESULTS: At the end of the training program, there were no
      significant results within the two groups. The endothelium-dependent vasodilation
      changed between T1 and T2 as follows: In the diabetic group, the endothelium
      dependent vasodilation at T1 and T2 was 5.1+/-3.6 and 4.9+/-2.5%, respectively.
      For the non-diabetics, the endothelium-dependent vasodilation was 6.8+/-4.5 and
      7.6+/-4.0% at T1 and T2, respectively. The endothelium-independent vasodilation
      in the diabetics was 10.5+/-5.6 at T1 and dropped to 8.7+/-4.1% at T2. The
      results for the non-diabetics were 13.2+/-5.8 and 12.3+/-6.3% at T1 and T2,
      respectively. The LVEF in the diabetics was 24.2+/-3.4% at T1, increasing to
      27.8+/-5.8% at T2. In the non-diabetics, the LVEF was 22.9+/-3.8 at T1 vs. 28.6+/
      6.9% at T2. In the groups of diabetics, the maximum oxygen uptake (VO2-max) was
      10.3+/-3.9 at T1 vs. 11.4+/-2.8 ml/kg/min at T2 and in the group of non-diabetics
      10.0+/-3.1 vs. 13.5+/-5.0 ml/kg/min. No correlations were found between the
      change in endothelium-dependent vasodilation and the increase in oxygen uptake.
      CONCLUSION: In our study, a program of physical exercise had no influence on
      endothelium-dependent or endothelium-independent vasodilation in insulin-treated
      type 2 diabetics or in non-diabetics with considerably reduced ejection fraction.
      In both groups, however, an exercise-related influence on medical parameters and
      physical performance could be observed.

PMID- 16598539
TI  - [Heart-diabetes-network--a concept for improved care for diabetic cardiovascular
      patients following cardiac surgical intervention].
AB  - Diabetic patients with heart disease are high risk patients for further vascular
      complications and therefore need an intensive and multimodal, interdisciplinary
      intervention. Due to the "segmentation" of medical care into primary care
      physician, specialists, acute and secondary care (rehabilitation) clinics, the
      patients will be taken care of on each individual segment with regard to the
      current requirements and specialties of the care provider. Such--each section,
      the GP, the cardiologist and the diabetologist, the heart centre and the
      rehabilitation clinic, represent individual and often strictly separate segments,
      which each will focus only on the acute problem and will collect (only) data
      required for the care in their particular segment. A multimodal approach can
      improve the chronic care and prognosis of these patients, as shown in several
      studies. The proposed network model should increase multi-disciplinary
      cooperation of the different levels of health care segments and overcome current
      barriers. It is thus necessary to provide common guidelines for diagnostic and
      therapeutic procedures and to improve communication between each individual
      sector. This could help to improve the secondary prevention in these high risk
      patients.

PMID- 16598540
TI  - [Medical care in times of DMPs].
AB  - It is by DMPs that the legislator intervened in medical care processes in Germany
      for the first time. Targets of treatment, diagnostic definitions and treatments
      were determined by legal order. The best available evidence was defined by law.
      The medical profession has come into conflict with this situation, as with regard
      to diabetes the legally established evidence-based contents are not apt to
      consensus, as they deviate significantly not only from the German guideline for
      the care of diabetes but also from the relevant international guide lines. The
      patient's entitlement to an appropriate treatment according to the state of the
      art is not accommodated due to this inconsistency. The cooperation between
      ambulatory and stationary care units as well as the cooperation between family
      practitioner and medical specialist is determined by the DMPs in terms of
      interfaces. Regarding the graduation within the care system an improvement can be
      anticipated.

PMID- 16598542
TI  - [Risk stratification of patients with diabetes mellitus undergoing coronary
      artery bypass grafting--a comparison of statistical methods].
AB  - Among the coronary bypass patients from our Datamart database, we found a
      prevalence of 29.6% of diagnosed diabetics. 5.2% of the patients without a
      diagnosis of diabetes mellitus and a fasting plasma glucose level > 125 mg/dl
      were defined as undiagnosed diabetics. The objective of this paper was to compare
      univariate methods and techniques for risk stratification to determine, whether
      undiagnosed diabetes is per se a risk factor for increased ventilation time and
      length of ICU stay, and for increased prevalence of resuscitation, reintubation
      and 30-d mortality for diabetics in heart surgery. Univariate comparisons reveals
      that undiagnosed diabetics needed resuscitation significantly more often and had
      an increased ventilation time, while the length of ICU stay was significantly
      reduced. The significantly different distribution between the diabetics groups of
      11 from 32 attributes examined, demands the use of methods for risk
      stratification. Both risk adjusted methods regression and matching confirm that
      undiagnosed diabetics had an increased ventilation time and an increased
      prevalence of resuscitation, while the length of ICU stay was not significantly
      reduced. A homogeneous distribution of the patient characteristics in the two
      diabetics groups could be achieved through a statistical matching method using
      the propensity score. In contrast to the regression analysis, a significantly
      increased prevalence of reintubation in undiagnosed diabetics was found. Based on
      an example of undiagnosed diabetics in heart surgery, the presented study reveals
      the necessity and the possibilities of techniques for risk stratification in
      retrospective analysis and shows how the potential of data collection from daily
      clinical practice can be used in an effective way.

PMID- 16598541
TI  - The metabolic syndrome and the heart--a considered opinion.
AB  - The metabolic syndrome (MS) is a multifactorial, heterogeneous group of risk
      factors for the development of cardiovascular disease. Here we review the
      evidence in support of the hypothesis that metabolic dysregulation of the body as
      a whole leads to contractile dysfunction of the heart due to an imbalance of
      substrate uptake (increased) and substrate oxidation (decreased). The
      consequences of this imbalance were already recognized 150 years ago by Virchow
      when he described "fatty atrophy" of the heart as a "true metamorphosis of the
      heart muscle cell."

PMID- 16598544
TI  - [Stent therapy with diabetic patients who have coronary artery disease].
AB  - When bare-metal stents are used, diabetic patients with coronary artery disease
      have a poorer prognosis than non-diabetic patients after coronary interventions.
      In clinical studies, it could be demonstrated that the disadvantage for diabetic
      patients is not present when drug-eluting stents are used. Today, two types of
      drug-eluting stents are clinically used: the sirolimus-eluting stent (Cypher) and
      the paclitaxel-eluting stent (Taxus). Even the high risk group of patients with
      in-stent stenosis can be efficiently treated with drug-eluting stents.

PMID- 16598543
TI  - [Diabetes mellitus and coronary artery disease--a high risk combination].
AB  - Patients with diabetes mellitus are often not recognized in clinical routine, but
      also not well characterized in clinical trials. As a diagnostic approach it is
      recommended to test fasting glucose and glycosylated hemoglobin (HbA1c) in every
      patient with coronary artery disease (CAD). HbA1c, in addition, provides
      important prognostic information. Patients with diabetes mellitus do have an
      enhanced cardiovascular risk in all stages and during all kind of interventions
      of CAD. However, diabetes is not equal to diabetes; risk modifying factors such
      as HbA1c, concomitant diseases and medication have to be considered. Absolute
      benefit of pharmacological therapies is also enhanced in patients with diabetes
      compared to non-diabetics. However, statins or anti-hypertensive treatment seem
      to be even more effective in reducing cardiovascular events than pure control of
      glucose levels alone. During percutaneous interventions (PCI) glycoprotein
      IIb/IIIa-inhibitors reduce mortality in diabetics, an effect which may be
      partially also achieved by Clopidogrel. Glitazones reduce restenosis rates;
      however, clinical end point studies are still ongoing. After PCI, restenosis may
      be a predictor of mortality in patients with diabetes. Whether drug eluting
      stents, besides effectively reducing restenosis, may also reduce hard clinical
      events in patients with diabetes remains to be demonstrated. Current available
      studies comparing PCI with bypass are limited due to not considered factors
      (stenosis morphology), randomization bias, and faster progress of technology
      compared to study termination. During an acute coronary syndrome/myocardial
      infarction, hyperglycemia is an adverse prognostic marker. However, so far
      studies using glucose-insulin-potassium (GIK) infusion have not been convincingly
      demonstrate to be beneficial.

PMID- 16598545
TI  - [Current evidence-based situation in coronary revascularization--CABG vs. PCI and
      diabetes?].
AB  - A variety of randomized, controlled trials comparing percutaneous coronary
      intervention (PCI) with coronary artery bypass grafting (CABG) found similar
      results in mortality but significant differences in number of reinterventions in
      favor of CABG. This work gives an overview about the relevance and limitations of
      these studies in line with newly published large scale observational studies,
      which reveal significantly lower mortality-rates in CABG patients. Emphasis is
      placed on the special situation in the diabetic patient.

PMID- 16598546
TI  - [Arterial grafts in coronary surgery for diabetic patients].
AB  - Surgical revascularization allows especially for the diabetic patient with
      coronary multi-vessel disease a superior long-termperspective compared to
      percutaneous coronary interventions. However, the specific advantages and also
      risks associated with the expanded use of arterial grafts as coronary conduits in
      diabetics are not clearly answered. A systemic analysis of the current literature
      underlines the following statements: The radial artery is, compared to the
      internal mammary artery, to a higher extent prone to atherosclerosis, especially
      in diabetic patients. Better long-term survival for patients with bilateral IMA
      grafts has also been assessed for diabetic patients. The risk of thoracic wound
      infections is not obligatory increased for diabetics with double IMA-grafts.
      Revascularization with radial arteries can be performed with low perioperative
      risks. Long-term results or studies on radial artery bypass grafting especially
      in diabetics are not available. In our own experience (3,548 isolated coronary
      operations, 01/2001 until 05/2005), diabetic patients have no increased
      perioperative mortality, even when using more complex arterial grafting.
      Conclusively, diabetic patients should also significantly benefit from the use of
      the second mammary artery. Regarding conduit quality, a second IMA appears
      favorable over the radial artery.

PMID- 16598547
TI  - [Should we avoid cardiopulmonary bypass with diabetic patients?].
AB  - In the peri-operative and post-operative course of coronary bypass operations,
      the diabetic patient is susceptible to complications that cause morbidity and
      mortality. Morbidity might best be conceptualized as the cumulative effect of the
      diabetic patient chronically at risk and a variety of surgically related insults,
      including surgical stress, anaesthesia, hypo- and hypertension, anaemia,
      dysrhythmias, de- or hyperhydration and cardiopulmonary bypass (CPB) that exceed
      the compensatory capacities of the patient. Because all these factors for adverse
      outcome coexist, it becomes difficult to determine which ones are most important.
      However, it is reasonable that, in the presence of generalized atherosclerosis
      affecting the aorta ascendens, carotids and the cerebral arteries, the
      interaction of CPB-associated embolization, hypoperfusion and inflammation may
      cause neurologic morbidity. Many physiologic alterations (such as non-pulsatile
      perfusion and hemodilution) occur during CPB and may worsen renal dysfunction in
      patients with diabetic nephropathy. Pulmonary dysfunctions, associated with
      diabetic microangiopathy, could be unmasked by atelectasis, capillary leak and
      other pathophysiological conditions developing after the use of extracorporeal
      circulation. Actually, there is evidence that with the avoidance of CBP and the
      use of adequate OPCAB (Off Pump Coronary Artery Bypass) techniques, by
      experienced teams, the incidences of neurological, renal and pulmonary
      complications decrease, in high-risk patients, e. g. diabetics, as well as in
      unselected cohorts. Because it is not possible to identify confidently those
      patients who are at risk for CPB-associated complications, we use a strategy
      where all CABG (Coronary Artery Bypass Grafting) are performed in OPCAB
      technique. The total OPCAB approach will in addition ascertain the development of
      organizational OPCAB routines and expertise. The process of re-engineering the
      unit towards total OPCAB needs systematic training and re-training of cardiac
      surgeons by surgeons, experienced in both, OPCAB surgery and knowledge transfer,
      according to the principles of continuing medical education (CME). Thus, the
      chances of the OPCAB technique improving the outcome of diabetic patients can be
      fully realized.

PMID- 16598549
TI  - [Diabetic nephropathy and heart surgery--prevention of perioperative acute renal
      failure].
AB  - The diabetic micro- and macroangiopathy leads to retinopathy, nephropathy,
      peripheral arteriosclerosis and coronary heart disease. Diabetic patients with
      identified comorbidity, such as nephropathy and peripheral arteriosclerosis, have
      the highest mortality after heart surgery. Long-term survival is better after
      coronary surgery compared to catheter angioplasty without or with stent
      implantation. Compared to "on-pump" surgery using a cardiopulmonary bypass, "off
      pump surgery is associated with a lower incidence of acute renal failure. In
      order to prevent acute renal failure in the course of heart surgery in diabetic
      patients, the following recommendations should be followed: i) the degree of
      renal damage (as indicated by the parameters: creatinine-clearance, albuminuria
      and blood pressure) has to be known before start of surgery; ii) the volume
      status (central venous pressure, central venous oxygen saturation) should be
      controlled tightly starting 12 hours before surgery; iii) if the volume status
      gets out of control post surgery, intensive care treatment using dopamine or loop
      diuretics should be stopped after 12-24 hours in case of treatment failure; iv)
      reduce the dose of or better avoid nephrotoxic substances (radio contrast media,
      antibiotics, non-steroidal pain killers; v) start effective renal replacement
      therapy early (daily intermittent or continuous hemodialysis, hemofiltration or
      hemodiafiltration).

PMID- 16598548
TI  - [Diabetes and heart transplantation].
AB  - Diabetes is frequently encountered in patients presenting with end-stage heart
      failure to be listed for transplantation. While diabetes used to be a contra
      indication for heart transplantation, careful preoperative evaluation and
      individualized postoperative medication lead to long-term outcome after heart
      transplantation equal to non-diabetic patients. About 1/3 of transplanted
      patients develop a post-transplant diabetes. Several risk factors have been
      identified leading to this condition. Mostly, post-transplant diabetes is of
      temporary nature. Several studies have shown no impact of diabetes on the
      incidence of rejection, malignancies, and transplant vasculopathy. However,
      glucose intolerance must be taken into consideration when planing
      immunosuppressive therapy since different medications have distinct impact on
      glucose metabolism after transplant. A multidisciplinary team allows for closely
      monitoring and treating patients with diabetes after heart transplant.

PMID- 16598550
TI  - [Diabetes and cerebrovascular disease].
AB  - Diabetes has significant implications for cardiac surgery. It is not only a major
      risk factor for coronary heart disease but also increases the risk for
      cerebrovascular complications during heart surgery. Surgical technique is pivotal
      for the outcome. "Off-pump" surgery carries a lower risk for stroke than
      conventional heart surgery. When a stroke happens, diabetes plays also a major
      role for the final outcome. Initial blood glucose levels during a stroke and
      final outcome are highly correlated. Consequently, patients with ischemic stroke
      after cardiac surgery should be treated according to the current criteria for
      stroke treatment. This includes strict monitoring of blood glucose level and
      avoidance of hypo- as well as hyperglycemia.

PMID- 16598551
TI  - [Diabetes, heart surgery and the peripheral arteries].
AB  - Peripheral arterial disease (PAD) is an under-recognized and underestimated
      complication of diabetes. Prevalence of PAD in diabetic patients is 25-30%. The
      main reason for underreporting is the largely asymptomatic nature of PAD in
      diabetes. It is important to diagnose PAD as soon as possible because PAD is an
      important marker for systemic atherosclerosis. Patients with claudication have
      approximately a 30% five-year mortality rate. PAD patients die 10 years earlier
      than patients without this atherothrombotic disease. About 70% of the PAD
      patients die from coronary heart disease, 5-11% die from stroke. PAD and diabetes
      are comorbid conditions and are associated with the risk of death from coronary
      artery bypass graft surgery. The prevalence of diabetes in patients who undergo
      cardiac surgery is 30% and the prevalence of PAD is 18%. The presence of PAD in
      diabetic patients had a similar 2-fold increase in the annual incidence of death
      compared with diabetic patients without PAD. The theory that diabetes and PAD
      together is associated with small vessel disease may play a role in the cause of
      the higher long-term mortality seen in at least two studies (Circulation 2004;
      suppl II: II/41-II/44).

PMID- 16598552
TI  - [Experiences collected in more than 2,300 diabetics undergoing coronary artery
      bypass grafting: patients with a specific risk profile].
AB  - BACKGROUND: The objective of this paper was to analyze demographic and clinical
      characteristics of diabetic patients undergoing coronary artery bypass grafting
      on the basis of a significant number of cases. METHODS: The data of 8,195
      patients who have undergone coronary bypass operations between 1996 and 2003 were
      analyzed. Non-diabetic patients (no DM), oral treated diabetics (DM oral) and
      insulin-treated diabetics (DM insulin) were compared in terms of their pre
      operative, intra-operative and post-operative characteristics. The statistical
      analyses were performed with the support of SPSS 11.5 under application of chi
      square and student-t tests. RESULTS: In cardiosurgery, diabetics differ in
      various ways from non-diabetic patients. They show a significantly higher
      prevalence of the known cardiovascular risk factors such as raised body mass
      index, age and hypertension. Furthermore they present a higher prevalence of
      vascular comorbidity such as peripheral vascular disease and carotid disease. At
      the postoperative stage, cerebral dysfunction occurred more often among the
      diabetic patients (no DM 5.2% vs. DM oral 7.3% vs. DM insulin 10.5%; p < 0.05),
      they suffered from apoplexies more frequently (no DM 1.9% vs. DM oral 2.1% vs. DM
      insulin 3.2%; p < 0.05), and they required re-intubation more frequently (no DM
      2.6% vs. DM oral 3.1% vs. DM insulin 5.6%; p < 0.05). Peri-operative mortality
      was highest in the group of insulin-treated diabetics (no DM 1.1% vs. DM oral
      1.6% vs. DM insulin 1.8%; p < 0.05). CONCLUSION: In coronary surgery, diabetic
      patients represent an especially challenging patient group with an independent
      risk profile, who require specific consideration as far as the selection of the
      operative approach, on, one hand, and the post-operative follow-up, on the other
      hand, are concerned.

PMID- 16598553
TI  - [Glucose control in cardiac disease].
AB  - The early and differentiated optimization of glucose level is essential for the
      improvement of the cardiovascular outcome. In all stages of cardiac disease, the
      primary goal is to reach near-normoglycemia. The DIGAMI-1 and 2 studies as well
      as the Munich Myocardial Infarction Registry successfully demonstrate, that the
      intensification of treatment with insulin therapy reduces the mortality of
      myocardial infarction. Glucose-insulin-infusion is advantageous with regard to
      the use of a well-controllable therapeutic approach. In non-acute cardiac
      disease, oral treatment strategies and insulin therapy are successful alone or in
      combination. Acarbose and metformin have been shown to be able to successfully
      prevent cardiovascular disease. New evidence of positive effects of glitazones
      with regard to reduction of the rate of restenosis and optimization of
      endothelial function is currently emerging. Prognosis of cardiovascular disease
      is significantly influenced by glucose control. There is evidence that the
      relationship between glycemia and cardiovascular events extends far beyond the
      diabetic threshold. This can be detected even in impaired glucose tolerance and
      the non-diabetic range. There is evidence that postprandial glycemia is crucial
      for the extent of cardiovascular risk. This has also been emphasized by the
      DECODE-study.

PMID- 16598554
TI  - [Postoperative antithrombotic treatment in diabetic patients].
AB  - Diabetes mellitus patients after aorto-coronary bypass operation constitute a
      patient cohort at largely increased risk for secondary coronary events.
      Antiplatelet agents and antithrombotic agents are applied for secondary
      prevention. Up to now, secondary prevention has not been addressed specifically
      in the cohort of diabetic patients after bypass operation. Hence therapeutic
      recommendations are derived from the global cohort of CAD patients and based on
      risk assessment rather than on specific data. Since diabetic patients after
      myocardial infarction are at particularly high risk, combined therapy with
      clopidogrel and ASS may be considered even with restricted resources in the
      health system. Oral anticoagulation with coumadin constitutes an effective
      alternative to dual anti-platelet therapy. Under specific conditions (ventricular
      aneurysms, EF < 30%, or certain conditions in coronary anatomy) oral
      anticoagulants should be considered more liberally than currently.

PMID- 16598555
TI  - [The importance of cholesterol-lowering in patients after coronary artery bypass
      surgery].
AB  - Patients with aortocoronary bypass surgery generally have a severe, advanced
      coronary atherosclerosis. An intensive risk-factor management should be of
      special importance in these patients. However, cholesterol treatment goals are
      the same for operated or non-operated patients with coronary artery disease.
      Effective cholesterol lowering does not only decrease the progression of
      atherosclerosis in native coronary vessels but also helps to prevent the
      development of atherosclerosis in venous bypass grafts. Clinical studies
      demonstrated that this leads to an improvement of clinical endpoints.
      Unfortunately we know from registries, that even in bypass patients recommended
      guidelines for cholesterol lowering are often not followed.

PMID- 16598556
TI  - [Diabetic nephropathy and ACE inhibitors].
AB  - The life expectancy of patients with type 2 diabetes and diabetic nephropathy is
      reduced; the main cause of death is cardiovascular disease. The majority of
      patients with renal replacement therapy are type 2 diabetics. Inhibition of the
      renin-aldosterone-angiotensin system is beneficial in diabetes mellitus. It
      reduces the incidence and slows the progression of nephropathy. ACE inhibitors
      are the accepted standard of care for nephropathy in type-1 diabetics; the role
      of ACE inhibitors versus angiotensin-receptor-blockers in type 2 diabetes is less
      clear. Large studies from the last 15 years and meta-analyses show a reduction of
      mortality of about 20% with ACE inhibitors in type 2 diabetic nephropathy;
      angiotensin-receptor-blockers have no documented effect on mortality yet, but do
      also slow the progression of nephropathy in type 2 diabetics. From these data and
      because of economic considerations, ACE inhibitors should be first choice therapy
      for diabetic nephropathy in type 2 diabetes mellitus.

PMID- 16598557
TI  - Atrial arrhythmias after cardiac surgery in patients with diabetes mellitus.
AB  - BACKGROUND: Postoperative atrial fibrillation (AF) is a common complication of
      cardiac surgery and has been associated with increased incidence of other
      complications and increased hospital length of stay (LOS). Prevention of AF is a
      reasonable clinical goal, and, consequently, many randomized trials have
      evaluated the effectiveness of pharmacological and non-pharmacological
      interventions for prevention of AF. To better understand the role of various
      prophylactic therapies against postoperative AF, a systematic review of evidence
      from randomized trials was performed. METHODS: MEDLINE search of English-language
      reports published between 1966 and July 2005 and a search of references of
      relevant papers were conducted. Clinical studies on AF after cardiac surgery were
      selected for this analysis. Relevant clinical information was extracted from
      selected articles. RESULTS: Postoperative AF is associated with increased
      morbidity and mortality and longer, more expensive hospital stays. Prophylactic
      use of beta-adrenergic blockers reduces the incidence of postoperative AF and
      should be administered before and after cardiac surgery to all patients without
      contraindication. Prophylactic amiodarone and atrial overdrive pacing should be
      considered in patients at high risk for postoperative AF (for example, patients
      with previous AF or mitral valve surgery). For patients who develop AF after
      cardiac surgery, a strategy of rhythm management or rate management should be
      selected. For patients who are hemodynamically unstable or highly symptomatic or
      who have a contraindication to anticoagulation, rhythm management with electrical
      cardioversion, amiodarone, or both is preferred. Treatment of the remaining
      patients should focus on rate control because most will spontaneously revert to
      sinus rhythm within 6 weeks after discharge. All patients with AF persisting for
      more than 24 to 48 hours and without contraindication should receive
      anticoagulation. CONCLUSIONS: AF frequently complicates cardiac surgery. Many
      cases can be prevented with appropriate prophylactic therapy. A strategy of
      rhythm management for symptomatic patients and rate management for all other
      patients usually results in reversion to sinus rhythm within 6 weeks of
      discharge.

PMID- 16598559
TI  - [We need interdisciplinary vessel-centered medicine].

PMID- 16598558
TI  - [Impaired glucose metabolism in patients with ischaemic heart disease].
AB  - Patients with ischaemic heart disease commonly have an impaired glucose
      tolerance. On the 2004 congress of the ESC, the 75-75-rule was announced,
      indicating that 75% of all diabetics die of cardiovascular complications, and
      that 75% of all patients with myocardial infarction have diabetes or an (often
      undiagnosed) impaired glucose tolerance. Data of our "Esslinger Koronarregister"
      confirm that diabetics and in particular women with diabetes have a higher
      mortality both after STEMI and NSTEMI. During acute myocardial infarction, a
      higher blood glucose level strongly correlates with increased mortality. This
      increased blood glucose level on the one hand is due to preexisting diabetes
      mellitus or metabolic syndrome, but on the other hand may be a marker of larger
      myocardial damage with excess katecholamine release. Recent data indicate that
      intensive glucose control results in a reduction of cardiovascular risk, e. g.
      the risk of sudden cardiac death. The data presented show that an early
      intervention in preclinical diabetics aiming at normalization of blood glucose
      control is necessary in order to reduce cardiovascular mortality.

PMID- 16598561
TI  - [Why is integrated health care appropriate for modern German cardiology?].
AB  - Integrated Health Care is a new tool in German legislative means to overcome the
      traditional separation of outpatient and inpatient health care sectors. In this
      paper, it is outlined, that cardiology meets several criteria that make the
      introduction of Integrated Health Care especially in cardiology promising. Among
      these criteria, evidence-based medicine, guideline-based medicine, good
      statistical information, large numbers of performed procedures, high costs of
      performed procedures, performance of procedures both in the outpatient and
      inpatient sectors, chronic course of treated diseases, a high degree of
      dependence on other medical specialities as well as a high need for the
      implementation of innovations in clinical cardiology are mentioned.Concluding,
      the paper explains the purposes of this supplement for the comprehension of
      different views on Integrated Health Care in cardiology as well as the
      information on already implemented Integrated Health Care. These experiences
      should facilitate the formulation of the requests for the cardiology community
      for new definitions of Integrated Health Care beyond 2007/ 2008.

PMID- 16598562
TI  - [What are the economic advantages of Integrated Health Care?].
AB  - Integrated Health Care and Managed Health Care are both tools to implement
      broader responsibilities of health care providers for the economic efforts of
      their activities. While Managed Care is quite common in the United States of
      America, experiences with such systems are sparse in Europe and Germany. With
      Integrated Health Care, new types of markets will emerge: not only a market for
      health care services, but also for insurance contracts, and for provision of
      care. The paper discusses different incentives arising from different health care
      systems.

PMID- 16598563
TI  - [Integrated Health Care in cardiology: substitution or addition of new tools?].
AB  - On the basis of broad statistical information about procedures and operations in
      German cardiology, the author discusses probable and already evident effects of
      emerging Integrated Health Care projects. Among those expectations, possibly a
      new group of services will emerge that adds rather than substitutes already
      existing services. By this effect no cost-containment, which is one of the
      legislative purposes for Integrated Health Care, will be achievable. Besides this
      pessimistic view, Integrated Health Care in cardiology has the potential to
      allocate financial funds in a more appropriate way than it is presently usual.
      For example, procedures that can be performed in outpatients, no longer need to
      be performed on inpatients for the only reason that hospitals are not entitled to
      do outpatient services.

PMID- 16598564
TI  - [Integrated Health Care in cardiology: have all players used their
      opportunities?].
AB  - From the view of one of the largest public health insurance companies, in this
      paper it is outlined that Integrated Health Care provides opportunities to
      influence the largely regional structures of health care supply. This insurance
      company has specialized in contracts for Integrated Health Care in cardiology in
      order to achieve sustainable solutions for all providers of invasive and
      interventional cardiology that are economically reasonable. But first of all,
      only evidence-based medical procedures and interventions based on clinical
      pathways are eligible for the contracts of this company. In outlining this, it
      becomes evident that by far not all German public health insurance companies have
      yet used their opportunity.

PMID- 16598565
TI  - [Third level centers in Integrated Health Care: no room, no interest, no needs?].
AB  - Third level health care providers are often highly integrated in the sense that
      they provide a broad variety of medical specialties. They mostly lack cooperative
      structures with physicians who are running private practices. By this
      "isolation", they realize disadvantages in the race for more patients. This is
      one reason why more university teaching hospitals are growingly interested in
      contracts for Integrated Health Care. Another field of growing needs for
      cooperative structures is rehabilitation to ensure achieved therapeutic success
      especially in highly specialized centers. The paper outlines these growing
      interests but also formulates preconditions for contracts which should be
      regarded if university hospitals are to become involved in Integrated Health
      Care.

PMID- 16598566
TI  - [The importance of integrated health care for private hospital owners].
AB  - About 60 to 70% of hospital services are non-urgent, elective procedures. At
      least in those indications, insurance companies can deliberately choose their
      partners among the providers. This forces hospital owners and other providers to
      enhance their performance, to sharpen their profile and to improve their image in
      the emerging market. Image in the market of health care is only acceptable as a
      race for improved quality and evidence-based clinical pathways with defined steps
      with full disclosure of the agreed indications. The next step will lead to
      management corporations as a link between partners, who will take over
      responsibility for reimbursement, reinsurance and all management tasks.
      Integrated Health Care is a promising first step.

PMID- 16598567
TI  - [How does the Brandenburg general public health insurance company use the
      opportunity of Integrated Health Care?].
AB  - New laws on Integrated Health Care gives the opportunity to destroy unnecessary
      barriers within German social security systems. The aim is to optimally create
      health care supply so that the large potentials within these systems do not
      vanish in the chaos of these complex structures. The second most important aim is
      to reduce the cost of health care. The Brandenburg AOK (general public health
      insurance company) accepts the challenges and focuses on innovative potentials.
      Integrated Health Care provides ample opportunities for this purpose.

PMID- 16598568
TI  - [Integrated Health Care in cardiology].
AB  - Integrated Health Care forces rethinking of all partners. Health care providers
      need to cooperate and have to face an emerging competition among themselves.
      Health insurance companies are no longer the common enemy, but a business partner
      on an individual basis. Rethinking has already commenced. The Barmer insurance
      company has initiated a considerable number of similar contracts with respect to
      Integrated Health Care in cardiology. One of the first contracts was agreed upon
      at Recklinghausen (it is reported later in this volume) and a couple of them have
      been concluded in the Berlin/Brandenburg region (which are also reported in this
      volume).A special feature is the support for the general disease management
      programs that have been initiated in light of the new laws beginning in 2000. The
      Barmer company will enroll some 500,000 patients with coronary artery disease in
      these programs.

PMID- 16598569
TI  - [Judicial opportunities and limitations of Integrated Health Care in cardiology].
AB  - Regulations of Integrated Health Care are capable of overriding the barriers of
      separated outpatient and inpatient health care. These regulations create a
      situation of competition among health care providers, but not among payers. Since
      the laws exclude common regulations of competition laws, antitrust laws and
      public procurement laws from Integrated Health Care, insurance companies gain a
      relatively strong position in the competition for contracts. This is even
      enforced by the fact that no health care provider is entitled to request a
      contract with a specific insurance company. The main result is that insurance
      companies can determine the contracts deliberately.

PMID- 16598570
TI  - [The need for insurance coverage in Integrated Health Care].
AB  - Any health care provider who engages in contracts for Integrated Health Care
      should identify, evaluate, quantify and protect against the risks which can
      emerge from such agreements. Presently insurance companies do not offer insurance
      coverage for guarantees that are stated by such contracts. Only delict-dependent
      responsibilities are covered by common insurances. Insurance companies are
      presently preparing adequate agreements to cover guarantees of Integrated Health
      care contracts.

PMID- 16598571
TI  - [Arguments in favor of Integrated Health Care as regular health care provision in
      cardiology].
AB  - Patients are not outpatients or inpatients, they are ill or healthy. Integrated
      Health Care provides a real chance to bring scientific innovations quickly from
      the laboratory to patients--and being paid for that. Although guidelines
      therefore are no compulsory exercise, they are tools to implement evidence-based
      use of innovative medical means. Health care providers should be reluctant to
      agree in guarantees for the success of medical therapies, since medical decisions
      may be influenced in different ways by that. Bureaucracy may hinder the spreading
      of Integrated Health Care; therefore simple regulations should be preferred.
      Reimbursement should not be designed according to conventional systems for
      outpatient or inpatient care, but as defined sums of money. That makes people
      sure to know what kind of contract they have agreed in.

PMID- 16598572
TI  - [Which reasons may hinder Integrated Health Care from spreading as regular health
      care provision in cardiology?].
AB  - Integrated Health Care may possibly be a training field for efficient patient and
      case management between different providers involved. In the medium term, those
      instruments should be developed further so that they are no longer merely tools
      for cost containment, risk transfer to the providers side and competition for the
      good risks in health care. In the present state Integrated Health Care--as many
      other new regulations--means a displacement of money from health care to
      administration. All participants are urged to check their contracts that the
      benefit for patients exceeds the price of the paper.

PMID- 16598573
TI  - [Criteria catalogue for Integrated Health Care in cardiology].
AB  - This paper comprises criteria for projects of Integrated Health Care in
      cardiology. With these criteria, projects can be assessed for their congruence
      with essentials that have been assigned by the German Cardiac Society, the
      Association of German Hospital Cardiologists and the Association of German
      Practice Cardiologists. The main purpose is to ensure that evidence-based
      medicine is the basis for the contracts and that all valid guidelines have been
      observed when services have been agreed. Possibly this paper may be the basis to
      award an approval to projects that meet all the criteria. This paper is no model
      contract.

PMID- 16598574
TI  - [Integrated Health Care in cardiology at Essen].
AB  - This paper reports in detail on a project of Integrated Health Care in cardiology
      at Essen, Germany. Information on the structure of the contract, the
      participants, the agreed claiming of benefits and provision of services are
      provided as well as relevant figures and contact data.

PMID- 16598575
TI  - [Integrated health care at Bad Krozingen].
AB  - This paper reports in detail on a project of Integrated Health Care in cardiology
      at Bad Krozingen, Germany. Information on the structure of the contract, the
      participants, the agreed claiming of benefits and provision of services are
      provided as well as relevant figures and contact data.

PMID- 16598576
TI  - [Integrated health care at Hamburg].
AB  - This paper reports in detail on a project of Integrated Health Care in cardiology
      at Hamburg, Germany. Information on the structure of the contract, the
      participants, the agreed claiming of benefits and provision of services are
      provided as well as relevant figures and contact data.

PMID- 16598577
TI  - [Integrated health care at Lubeck].
AB  - This paper reports on a project of Integrated Health Care in cardiology at
      Lubeck, Germany. Information on the structure of the contract, the participants,
      the agreed claiming of benefits and provision of services are provided as well as
      relevant figures and contact data.

PMID- 16598578
TI  - [Integrated health care at Recklinghausen].
AB  - This paper reports in detail on a project of Integrated Health Care in cardiology
      at Recklinghausen, Germany. Information on the structure of the contract, the
      participants, the agreed claiming of benefits and provision of services are
      provided as well as relevant figures and contact data.

PMID- 16598579
TI  - [Integrated health care at Potsdam].
AB  - This paper reports in detail on a project of Integrated Health Care in cardiology
      at Potsdam, Germany. Information on the structure of the contract, the
      participants, the agreed claiming of benefits and provision of services are
      provided as well as relevant figures and contact data.

PMID- 16598580
TI  - [Development of cardiology care in Berlin].
AB  - Berlin's local government is presently trying to implement new regulations for
      cardiology health care providers. By definition of the criteria for second and
      third level centers, hospitals should be assessed as to whether they, in the
      future, will be entitled to provide treatment for patients with acute coronary
      syndrome. The author, who has been involved in the construction of this project
      as a representative of public health insurance companies, reports on details of
      this project. Integrated Health Care will be a major contribution of this
      regulation.

PMID- 16598581
TI  - [A federal project of Integrated Health Care in cardiology].
AB  - This paper reports in detail on a project of Integrated Health Care in cardiology
      at the federal level in Germany. Information on the structure of the contract,
      the participants, the agreed claiming of benefits and provision of services are
      provided as well as relevant figures and contact data.

PMID- 16598582
TI  - [Integrated health care at Nuremberg].
AB  - This paper reports in detail on a project of Integrated Health Care in cardiology
      at Nuremberg, Germany. Information on the structure of the contract, the
      participants, the agreed claiming of benefits and provision of services are
      provided as well as relevant figures and contact data.

PMID- 16598583
TI  - [Relevant laws for Integrated Health Care].

PMID- 16598584
TI  - [Integrated Health Care--fundamental change of paradigms].
AB  - Integrated Health Care provides new opportunities to overcome the traditional
      separation of inpatient and outpatient care in Germany. In this paper from the
      view of the government, one of the most dedicated and involved originators of the
      legislative formulation takes the opportunity to outline the purposes and
      expectations of the government and parliament in implementing the new
      regulations. Those purposes are high-quality health care for patients, relief of
      bureaucracy for health-care providers and economically reasonable conditions for
      payers.

PMID- 16598585
TI  - [Integrated health care in cardiology. Foreword].

PMID- 16598588
TI  - "Thrombolysis" by a neuromuscular blocking agent.

PMID- 16598587
TI  - How to revascularize patients with diabetes mellitus: bypass or stents and drugs?
AB  - The diabetic patient is at high risk for coronary artery disease. Incidence as
      well as severity of the disease is highly increased in comparison to non-diabetic
      patients. The revascularization of the diabetic patient is a great challenge,
      since the longterm results are disappointing when compared to non-diabetic
      patients. The success of coronary artery bypass grafting is limited by increased
      perioperative mortality and a faster occlusion of especially venous bypass
      grafts. In percutaneous interventions the excessive high restenosis rates worsen
      longterm results. Several clinical trials investigated the outcome of the two
      revascularization strategies and could demonstrate at least a tendency towards
      better results when the operative approach was chosen. Particularly, the BARI
      trial showed reduced mortality for surgery when compared to percutaneous coronary
      interventions. However, in this trial, in 87% of patients undergoing bypass
      surgery all stenoses were successfully treated, whereas in patients undergoing
      percutaneous coronary intervention only 76% of all stenoses were primarily
      successfully treated. In addition, no stents were used in this trial.Furthermore,
      the enrollment of the previous trials dates one decade ago. These trials do
      therefore not necessarily represent the current standard therapy, especially for
      percutaneous coronary interventions. The restenosis rate could be decreased in
      recent years by means of drug-eluting stents and an aggressive antiplatelet
      therapy from more than 50% to less than 10% leading to considerably improved long
      term results. Therefore, percutaneous coronary interventions have developed to be
      a reasonable alternative to bypass surgery. Different clinical trials are
      currently underway (BARI 2D, CarDIA, FREEDOM) comparing the outcome of the two
      approaches.

PMID- 16598589
TI  - Temporary trans-coronary pacing by coated guidewires: a safe and reliable method
      during percutaneous coronary intervention.
AB  - Relevant bradycardias during percutaneous coronary intervention (PCI) are a rare
      event, but they require immediate therapy by temporary pacing. However,
      transvenous pacing is associated with frequent and severe complications.
      Therefore, we wanted to evaluate the safety and reliability of trans-coronary
      pacing by means of a PCI guidewire. Coronary pacing was applied to 70 consecutive
      patients undergoing PCI. Pacing was performed before and after PCI in a unipolar
      setting using standard guidewires as a cathode and a skin electrode as an anode.
      Both were connected to an external pacemaker. Coronary pacing (maximum output at
      10 V, impulse duration 2.5 ms) was effective in 60 of 70 patients (85.7%).
      Successful pacing was achieved in the LAD and diagonal branches in 90% (27 of 30
      Pts.), in the LCX and marginal branches 84.2% (16 of 19 Pts.) and in the RCA in
      81% (17 of 21 Pts.). Pacing thresholds were comparable in all vessels within a
      range of 1-10 V averaging 6.6 +/- 2.3 V before and 6.6 +/- 2.2 V after PCI. The
      impedance ranged from 190-544 Omega with mean pacing impedance for coronary
      pacing of 424 Omega before and 416 Omega after PCI, respectively. Significant
      bradycardias during PCI occurred in 7 cases (10%). In three cases (4.3%)
      temporary coronary pacing became necessary at a maximum pacing duration of 3 min.
      There were no severe side effects. Coronary spasm occurred in 3 cases (4.3%)
      after pacing and was promptly reversible after intracoronary application of
      nitroglycerine. It is concluded that coronary pacing is a safe and feasible
      method for the treatment of bradycardias during PCI. It avoids additional venous
      puncture under hemodynamically unstable conditions and subsequent transvenous
      pacing, which is accompanied by potentially severe complications and additional
      costs.

PMID- 16598590
TI  - Differential antiplatelet effects of angiotensin converting enzyme inhibitors:
      comparison of ex vivo platelet aggregation in cardiovascular patients with
      ramipril, captopril and enalapril.
AB  - BACKGROUND: Increasing evidence suggests that angiotensin converting enzyme (ACE)
      inhibitors exert antithrombotic effects. Based on the assumption of differential
      effects of various ACE inhibitors on coagulation, the aim of the present study
      was to evaluate the coagulative activities of cardiovascular (CV) patients
      treated with either ramipril, captopril, and enalapril, and to compare these with
      patients treated with established antithrombotics such as aspirin (ASA) and
      clopidogrel or none of these medication. METHODS: Blood samples of 320 CV
      patients with coronary artery disease and/or arterial hypertension were analyzed
      by wholeblood aggregometry. Platelet aggregation was determined by measuring the
      increase in impedance across paired electrodes in response to the aggregatory
      agents collagen and adenosine diphosphate (ADP), respectively. These data were
      correlated with medical treatment. RESULTS: Platelet aggregation was attenuated
      ex vivo by ramipril and captopril as well as by ASA and clopidogrel. While
      collagen-induced platelet aggregation was significantly reduced by ramipril (35%;
      P <0.01) and captopril (27%; P = 0.01), no change was seen with enalapril. After
      induction with ADP, platelet aggregation was reduced in the presence of captopril
      therapy by 46% (P <0.05). There was a trend of inhibition with ramipril (32%, P =
      n.s.), whereas no antithrombotic effect was seen with enalapril. CONCLUSION: Our
      findings demonstrate that ACE inhibitors decrease platelet aggregation ex vivo.
      The differential antiaggregatory profile may explain at least in part different
      effects of ACE inhibitors on cardiovascular endpoints as observed in large
      clinical trials.

PMID- 16598591
TI  - Trapidil is as effective as isosorbide-dinitrate for treating stable angina
      pectoris: a multinational, multicenter, double-blind, randomized study.
AB  - OBJECTIVE: Nitrates have long been used in the treatment of stable angina
      pectoris. We set out to show that trapidil, a triazolo-pyrimidine with a mode of
      action different from that of nitrates, is not inferior to isosorbide-dinitrate
      (ISDN) in the treatment of this clinical syndrome. PATIENTS AND METHODS: We
      studied the efficacy of 200 mg trapidil (t.i.d.) vs. ISDN (20 mg b.i.d.) in
      patients with chronic stable angina treated for 12 weeks. The therapeutic effect
      was measured in terms of responder rate as change in total exercise time (TET) by
      at least 60 seconds using the bicycle ergometer test. RESULTS: A total of 648
      patients were included in the study. Responder rates in the Per- Protocol (PP)
      population (n = 529) were 50.4% (n = 133) in the trapidil group and 52.5% (n =
      139) in the ISDN group (p = 0.233). As the lower non-inferiority limit (-15%) was
      clearly excluded from the 95% CI (pp: -10.6%, +6.4%; ITT -9.7%, 5.7%), non
      inferiority of trapidil compared to ISDN can be concluded. Trapidil 200 mg t.i.d.
      combined with short-acting NTG prn as rescue medication over 12 weeks in subjects
      with chronic stable angina pectoris proved to have similar effects on TET and on
      other clinical endpoints as ISDN 20 mg b.i.d. The secondary efficacy analyses did
      not reveal any clinically relevant differences between treatment groups, and were
      not in conflict with the non-inferiority claim. Patients in the ISDN group had
      significantly more headache (34.1%; n = 110) compared to those taking trapidil
      (19.3%, n = 62; p <0.0001). CONCLUSIONS: Overall results of this study show that
      both drugs are equally effective and safe for the short-term treatment of
      patients with chronic stable angina pectoris and that trapidil can be considered
      as therapeutically equivalent to ISDN.

PMID- 16598592
TI  - Transcatheter occlusion of a large intercostal side-branch of left internal
      mammary artery bypass with detachable platinum coils.
AB  - Intercostal branches of the internal mammary artery (IMA) are usually tied off
      during IMA-bypass surgery. Some side-branches may be missed, however, due to
      anatomical variants or during minimal invasive procedures with limitation of the
      surgeon's ability to ligate proximal branches. There are a number of reports in
      the literature describing interventional closure of side-branches using Gianturco
      coils. Following embolization or malposition, however, these coils may be
      extremely difficult to retrieve from coronary arteries. We report about
      interventional embolization of a IMA side-branch with detachable micro-coils in a
      patient with symptomatic coronary steal. Detachable coils are safer than
      Gianturco coils and are an effective method to abolish symptomatic coronary steal
      due to unligated intercostal branches of the IMA graft.

PMID- 16598593
TI  - Bicuspid aortic valve: evaluation of the ability to participate in competitive
      sports: case reports of two soccer players.
AB  - Two competitive soccer players aged 23 and 17 years with known bicuspid aortic
      valve presented for sports-medical pre-participation screening. Both athletes
      were well trained and had a maximal oxygen uptake of 61 and 60 ml/min/kg,
      respectively. Echocardiography of the first athlete revealed an eccentric
      hypertrophy of the left ventricle (end-diastolic diameter 58-59 mm, septal and
      posterior myocardial wall thickness 12-13 mm) with good systolic and diastolic
      function and a functional bicuspid aortic valve with mild regurgitation. In the
      second athlete, echocardiography showed a bicuspid aortic valve with moderate
      regurgitation and a relative stenosis, a hypertrophied left ventricle (end
      diastolic diameter 62-63 mm, myocardial wall thickness 13-16 mm) and dilation of
      the ascending aorta of 46 mm, which was confirmed by magnetic resonance imaging.
      According to international guidelines, the first athlete was allowed to
      participate in competitive soccer. Nevertheless, regular cardiologic examinations
      in intervals of 6 months were recommended. In the second case, the athlete was
      not allowed to take part in competitive sports due to the extended ecstasy of the
      ascending aorta and the concomitant risk of an aortic rupture. In addition, the
      left ventricular hypertrophy has to be considered as pathologic. Therefore, the
      athlete was only allowed to exercise in recreational sports with low and easily
      controllable intensities. CONCLUSION: In athletes with bicuspid aortic valve,
      besides the evaluation of the aortic valve, physiologic adaptations of the heart
      have to be differentiated from pathological changes. Furthermore, the aorta
      deserves special attention, because in the case of a (probably genetically
      determined) dilated ascending aorta, an elevated risk for aortic rupture is
      present during intensive and competitive exercise. A general judgement in
      athletes with bicuspid aortic valves on their ability to participate in
      competitive sports is, therefore, not possible.

PMID- 16598594
TI  - Restrictive cardiomyopathy in a patient with primary hyperoxaluria type II.
AB  - This is the first report of a cardiac manifestation of a primary hyperoxaluria
      type II (PH II) with the hemodynamic characteristics of a severe restrictive
      cardiomyopathy. PH II is a rare inherited metabolic disease characterized by a
      deficiency of D-glycerate dehydrogenase, which has also glyoxylate reductase
      activity. This defect causes an accumulation of hydroxypyruvate the precursor of
      oxalate. The renal excretion of oxalate is impaired causing a deposition of
      oxalate mainly in the kidneys. To date, less than fifty cases have been reported.
      Systemic oxalosis in PH II is an occasional finding; thus far, myocardial
      oxalosis due to PH II has never been reported. Described is the case of a 41 year
      old male with renal failure and severe neuropathy of unknown cause, who underwent
      endomyocardial biopsy under the suspicion of cardiac amyloidosis.
      Echocardiography and cardiac catheterization showed a severe restrictive
      cardiomyopathy; endomyocardial biopsy established the diagnosis of oxalosis.
      Plasma oxalate levels were markedly increased, therefore a liver biopsy was
      performed. Immunoreactivity for D-glycerate dehydrogenase/ glyoxylate reductase
      was absent and activity of the enzyme was < 5% of normal. In summary, these
      findings established the diagnosis of a restrictive cardiomyopathy due to PH II.

PMID- 16598595
TI  - Entrapment of pacemaker lead by a large net-like Eustachian valve within the
      right atrium.
AB  - During pacemaker implantation in a patient with permanent atrial fibrillation, it
      remained impossible to advance a passive fixation lead with fins through the
      right atrium. However, a lead with a retractable screw easily passed the right
      atrium and was positioned in the right ventricle. Transesophageal
      echocardiography revealed an extensive net-like perforated Eustachian valve
      within the right atrium that had caused entrapment of the anchor fins during lead
      implantation. Remnants of embryonal structures within the right atrium should be
      considered a rare possible barrier during pacemaker implantation.

PMID- 16598596
TI  - Patchy or homogenous myocardial fibrosis in Becker muscular dystrophy? Comments
      on Suselbeck et al., Z Kardiol 94:465-468/2005.

PMID- 16598597
TI  - New perspective in arrhythmia and heart failure monitoring.

PMID- 16598598
TI  - Management of atrial fibrillation--what are the possibilities of early detection
      with home monitoring?
AB  - A large number of patients implanted with dual-chamber pacemakers exhibit
      symptoms of recurrent or new atrial fibrillation. Scheduling follow-up visits for
      every 6-12 months in this setting may be disadvantageous on three grounds. First,
      delayed information about the onset of atrial fibrillation does not allow an
      immediate reaction with pharmacological or dedicated pacing therapy. Second, the
      efficacy of the chosen therapy cannot be evaluated until the next scheduled
      follow-up. Third, real-time awareness of a significant atrial fibrillation burden
      is critical to use appropriate anticoagulation therapy for the prevention of
      thromboembolic events. The new Home Monitoring technology (Biotronik, Berlin)
      offers real-time transmission of diagnostic data stored in the pacemaker memory
      to the physician. This may represent a useful tool for the detection and
      treatment of patients with atrial fibrillation. Daily documentation of atrial
      rhythm via Home Monitoring allows a quick reaction to the onset of atrial
      fibrillation and real-time control of the therapeutic efficacy. The ongoing,
      international, randomized Home-PAT clinical trial aims at defining and
      quantifying the importance of Home Monitoring for the diagnosis and treatment of
      atrial fibrillation in patients with dual-chamber pacemakers.

PMID- 16598599
TI  - The role of remote monitoring in the reduction of inappropriate implantable
      cardioverter defibrillator therapies.
AB  - Implantable cardioverter defibrillators (ICDs) with the integrated Home
      Monitoring feature use dedicated mobile phone and internet links to provide the
      physicians and technicians in the ICD clinic with the essential device- and
      arrhythmia-related data stored in the ICD diagnostic memory. Various counters,
      graphs and intracardiac electrograms are automatically transmitted via Home
      Monitoring each day to allow prompt, remote presentation of arrhythmias or
      detection of technical problems. One of the most inconvenient side-effects of the
      ICD therapy is inappropriate intervention of the device. Home Monitoring data can
      help the physician to identify and subsequently reduce the incidence of
      inappropriate ICD therapy.

PMID- 16598600
TI  - IEGM-online based evaluation of implantable cardioverter defibrillator therapy
      appropriateness.
AB  - Appropriate and inappropriate therapies of implantable cardioverter
      defibrillators have a major impact on morbidity and quality of life in ICD
      recipients. Intracardiac electrograms (IEGMs) stored in the ICD have been shown
      to be essential for differentiating appropriate and inappropriate ICD therapies.
      The recently introduced third generation of ICD Home Monitoring offers remotely
      transmitted IEGMs (IEGM-online). Hence, the appropriateness of ICD therapies
      might be remotely assessed. Validation of these electrograms is currently being
      performed in the RIONI study. A total of 210 episodes will be collected by about
      40 European clinical centers. The study primarily investigates whether the IEGM
      online based evaluation of the appropriateness of the ICD's therapeutic decision
      following a tachyarrhythmia episode detection is equivalent to the evaluation
      based on the complete ICD episode holter. The evaluation is independently
      performed by an expert board of three experienced ICD investigators. The
      equivalence of the two methods is accepted if the conclusions deviate for less
      than 10% of all evaluated IEGMs. Secondary endpoints investigate the IEGM-online
      usefulness in more detail. The conclusion of the study is expected by mid of
      2007. RIONI has successfully been started for proving the reliability of IEGM
      online. The expected results will significantly influence the efficacy of Home
      Monitoring based patient management.

PMID- 16598601
TI  - Predicting mortality and rehospitalization in heart failure patients with home
      monitoring--the Home CARE pilot study.
AB  - The increasing worldwide prevalence of heart failure is associated with numerous
      and protracted hospital admissions. The multidisciplinary team approach together
      with telemonitoring aims at reducing the number of rehospitalizations, length of
      hospital stay, and mortality rates. Novel cardiac resynchronization therapy (CRT)
      devices have a Home Monitoring capability, offering wireless, everyday transfer
      of the essential status and therapy data to the attending physician. The
      transmitted data include potential predictors of death or hospitalization, such
      as the onset of atrial and ventricular arrhythmias, duration of physical
      activity, mean heart rates over 24 h and at rest, percentage of CRT delivered,
      and lead impedances. We present here interim results of the prospective,
      longitudinal, multicenter Home CARE Phase 0 study, conducted in 123 patients
      (age: 67+/-9 years, 83% male) with clinical indication for CRT. Twenty-nine
      patients (24%) received a CRT pacemaker, 52 (42%) a prophylactic implantable
      cardioverter defibrillator (ICD), and 42 (34%) had other ICD indications. All
      devices have an integrated Home Monitoring feature. In a mean (interim) follow-up
      period of 3 months (9194 observational days), 11 unplanned rehospitalizations of
      cardiovascular etiology and 9 deaths occurred. In 70% of the rehospitalization
      events, the retrospective analysis of transmitted data via Home Monitoring
      revealed an increase in mean heart rate at rest and in mean heart rate over 24 h
      within 7 days preceding hospitalization. A decrease in the percentage of CRT was
      observed in 43% and a reduction in the patients' daily activity in 30% of
      rehospitalized patients. These interim findings suggest that Home Monitoring data
      may predict events leading to hospitalization and encourage further research.

PMID- 16598602
TI  - What evidence do we have to replace in-hospital implantable cardioverter
      defibrillator follow-up?
AB  - INTRODUCTION: Due to the increasing number of patients with an implantable
      cardioverter defibrillator (ICD), new options for ICD patient follow-up
      management are required. METHODS: Patients with ICD indication according to the
      guidelines received an ICD with Home Monitoring technology. The devices enabled
      the transmission of the relevant episode, therapy, and system integrity data.
      Patients were followed for 12 months with routine controls every 3 months. The
      physician analyzed the Home Monitoring data before the routine follow-up visit
      (FU) and gave a forecast on the necessity of the pending FU, which was compared
      with the evaluation after the FU. Based on the derived forecast reliability, a
      patient management scheme was developed and its impact on patient safety was
      assessed retrospectively. RESULTS: A total of 271 patients were enrolled (40 f,
      mean age 62+/-12 years, mean LVEF 39+/-15%, 65% ischemic heart disease, 20%
      cardiomyopathy) and followed for 339+/-109 days. Of 908 pairs of Home Monitoring
      data and FU data evaluation, 129 there were false negative results for 92
      patients. Safety concerns from false negative forecasts can be minimized with a
      patient management scheme containing the following elements: 1) never skip the
      first routine FU; 2) never skip a routine FU for a patient having already shown
      pacing threshold problems; 3) perform FU following hospitalizations; 4) perform
      FU following episode detection by the ICD; and 5) perform a routine FU if the
      patient reports symptoms. The retrospective analysis showed, that if the patients
      had been managed using this scheme, 503 of 1079 routine FU could have been
      skipped with only one safety concern, a three month delay in the detection of
      silent paroxysmal atrial fibrillation in one patient. CONCLUSIONS: Home
      Monitoring in ICD therapy over 12 months is feasible. The data transmitted
      relevantly contribute to a remarkable reduction of follow-up burden and enable
      the individualization of routine follow-up.

PMID- 16598603
TI  - Home Monitoring: what can we expect in the future?
AB  - The Home Monitoring of implanted cardiac rhythm management devices developed by
      Biotronik (Berlin, Germany) is a new useful tool for monitoring patients. Home
      Monitoring provides access to technical and clinical data, allowing almost
      continuous patient surveillance. The implanted defibrillators and pacemakers
      transmit encrypted messages, which are automatically analyzed in the Home
      Monitoring Service Center and sent to the physician. The expected benefit of this
      kind of data transmission is an improvement in patient follow-up and early
      detection of changes in the rhythmologic state of the patient. However, these new
      tools raise several questions, which will require an answer in the nearest
      future. These questions focus on safety and economic aspects, and on the
      liability of the physician and the manufacturer. Technological improvement is
      also expected.

PMID- 16598604
TI  - [Pathophysiology of chronic heart failure].
AB  - Heart failure is a progressive and often fatal disease process. In general, the
      pathophysiologic mechanisms responsible for progressive myocyte dysfunction and
      cell loss, cardiac remodeling and arrhythmias involve signaling mechanisms that
      alter myocardial gene expression. These changes in gene expression are complex
      and involve contractile proteins, ion channels, Ca(++) handling, apoptosis, cell
      metabolism, the extracellular matrix, signal transduction pathways and growth
      factors. In the failing heart, several changes occur in cardiac adrenergic
      receptor-signal transduction pathways. The most striking of these changes occur
      in beta-adrenergic receptors, and of the changes in beta-adrenergic receptors
      beta1-receptor down-regulation is the most prominent. Other changes include
      uncoupling of beta2-adrenergic receptors and increased activity of the inhibitory
      G-protein. Most of these changes appear to be related to increased activity of
      the adrenergic nervous system, i.e. increased exposure to norepinephrine.
      Antagonists of the adrenergic nervous system may improve left ventricular
      function and outcome in patients with heart failure. This fact supports the
      notion that activation of these neurohormonal systems exerts a net long-term
      detrimental effect on the natural history of chronic heart failure and that
      myocardial adrenergic desensitization phenomena are at least partially
      maladaptive in the setting of left ventricular dysfunction. In addition to
      functional alterations structural remodeling plays a major role in the
      progression of various heart diseases to congestive heart failure. Major
      contributors to this remodeling process in the heart include alterations in
      myocyte shape, myocyte number and extracellular matrix. However, it is unclear as
      to which of these changes is most critical in the development of congestive heart
      failure, and this may vary by etiology.

PMID- 16598605
TI  - [Cardiac resynchronization therapy for heart failure - from experimental pacing
      to evidence-based therapy].
AB  - Within the last decade, cardiac resynchronization therapy (CRT) has become an
      evidence-based cornerstone for a subset of patients with chronic heart failure.
      For those, who suffer from ischemic or non-ischemic cardiomyopathies at NYHA III
      or IV, have sinus rhythm, a left bundle branch block and a left ventricular
      ejection fraction below 35%, CRT has evolved as an important treatment option
      with promising results. Numerous studies have shown that in these patients
      pacemaker-mediated correction of intra- and interventicular conduction
      disturbances can improve not only clinical symptoms, exercise tolerance and the
      frequency of hospitalizations, but even more important the overall mortality.
      These clinical results are due to several functional aspects. In the failing
      heart characteristic intra- and interventricular alterations in electrical
      conduction result in mechanical asynchrony that leads to an abnormal contraction
      of the left ventricle with delayed activation of the lateral wall, a paradoxical
      septal movement, a reduced diastolic filling and a mitral regurgitation due to
      dyssynchrony of papillary muscle activation. It is conceivable that these
      functional changes have fatal consequences for the failing heart. AV-optimized
      left- or biventricular stimulation by modern pacemakers can correct the
      pathological dyssynchrony, thereby improving cardiac function and clinical
      outcome in these patients. Although tremendous progress in cardiac
      resynchronization therapy has been made during the last decade, a couple of
      questions still need to be resolved. Critical issues are the identification of
      patients, who will predictably benefit from CRT, the value of CRT-pacemakers
      versus CRT-ICDs, and the usefullness of CRT in patients with atrial fibrillation.

PMID- 16598606
TI  - [Drug treatment of chronic heart failure].
AB  - Drug treatment of chronic heart failure is undergoing continuous modifications
      according to the data of new trials. Treatment has to be adjusted to current
      guidelines. The state of the art of medical treatment of chronic heart failure is
      addressed in this report.

PMID- 16598607
TI  - [Differential diagnosis of dyspnea - significance of clinic aspects, imaging and
      biomarkers for the diagnosis of heart failure].
AB  - Dyspnea is a frequent reason for emergency consultations in hospitals or
      community medical facilities. Besides heart failure, a wide variety of other
      disorders may cause this symptom. Thus, early and accurate differential diagnosis
      is mandatory in order to facilitate rapid institution of appropriate therapy.
      This CME article elaborates on the specific usefulness of traditional diagnostic
      tools as history, symptomatology and physical signs along with chest X-ray and
      ECG and the more recently introduced natriuretic peptides to discriminate heart
      failure from other causes of dyspnea in the emergency setting. According to a
      systematic search and meta-analysis of the respective literature, several
      features from history and physical examination as well as pulmonary congestion on
      chest X-ray, atrial fibrillation and a high level of confidence of the initial
      clinical judgment indicate a cardiac cause of dyspnea with high specificity, but
      less sensitivity. Thus, in patients presenting with one or several of these
      characteristic features, little further diagnostic yield is to be expected from
      natriuretic peptides. If, however, the suspicion of heart failure remains
      unsettled by these means, determination of biomarkers may be helpful, although it
      needs to be considered that moderately elevated levels have only a limited
      specificity in particular in elderly patients with comorbidities. As also
      recognized by the European Guidelines for diagnosis and treatment of chronic
      heart failure, a BNP level of <100 pg/ml has proven particularly useful for
      excluding heart failure. Thus, a directed history, symptoms, physical findings,
      chest-X-ray and ECG remain the diagnostic mainstay. If the diagnosis cannot be
      established by these traditional tools, BNP or NT-proBNP testing may be very
      helpful, especially for ruling out heart failure.

PMID- 16598608
TI  - [Working instructions in the cardiac catheter laboratory. According to paragraph
      18 (2): Radiographic regulation for a radiography facility for the use of x-rays
      with humans as a model].

PMID- 16598609
TI  - [Recommendations for the quality improvement of interdisciplinary care of adults
      with congenital heart anomalies].

PMID- 16598610
TI  - [Position paper on the indication for and implementation of interventional
      treatment of extracranial carotid stenosis].

PMID- 16598612
TI  - Pregnancy and delivery of a healthy baby in autoimmune Lambert-Eaton myasthenic
      syndrome.

PMID- 16598611
TI  - CSF prostaglandin D synthase is reduced in excessive daytime sleepiness.
AB  - Lipocalin-type prostaglandin D synthase (L-PGDS) is a brain enzyme, which
      produces prostaglandin D(2), a substance with endogenous somnogenic effects.
      Using a standardized protocol for immunonephelometric determination of
      cerebrospinal fluid (CSF) L-PGDS levels, we show that CSF L-PGDS levels are
      significantly lower in 34 patients with excessive daytime sleepiness when
      compared with levels in 22 healthy controls. Thus, L-PGDS may represent the first
      neurochemical measure of excessive daytime sleepiness.

PMID- 16598613
TI  - Denial in the first days of acute stroke.
AB  - Denial is a disorder of self-awareness that is frequent after acute stroke, with
      potential negative influence in the care of patients. The aim of this study was
      to describe the presence and correlates of denial in acute stroke. We assessed
      denial in a sample of 180 consecutive acute stroke patients (< or =4 days) and in
      a control group of 50 acute coronary patients using the Denial of Illness Scale
      (DIS).41% (74) acute stroke patients (mean DIS score=4.1, SD=2.2, range 0 to 10)
      and 24% (12) acute coronary patients (mean DIS score=3.2, SD=1.5, range 0 to 10)
      presented denial (chi(2)=4.19, p=.04; U=3405.50, p=.01). Denial was more frequent
      and severe in patients with lower educational level (chi(2) = 5.04, p=.04;
      U=2110.50; p=.01), neglect (chi(2) = 21.38, p=.00; U=1130.50; p=.00), cognitive
      impairment (chi(2) = 6.27, p=.02; U=1181.50; p=.01) and after hemispherical
      lesions (chi(2) =4.68, p=.05; U=1982.50; p=.04). In logistic regression low
      educational level, neglect and cognitive impairment were independent factors
      predicting denial in stroke patients (R(2)= 21%). Patients with denial can
      express depressive symptoms. Patients with denial had a worse outcome at
      discharge (chi(2) =4.91, p=.04; U=2918.00; p=.03). Denial is a frequent
      phenomenon after acute stroke. We propose that there is a multifactorial model
      for the emergence of denial, lower educational as a predisposing condition, and
      acute stroke due to hemisphere lesion and causing neglect and cognitive
      impairment as precipitating events. All these factors limit patients' assessment
      of their condition and body functions.

PMID- 16598615
TI  - Paroxysmal focal dystonia with sensory symptoms secondary to cortical
      oligoastrocytoma.

PMID- 16598614
TI  - Hypocretin-1 (orexin A) levels are normal in Huntington's disease.

PMID- 16598616
TI  - [Anatomy, special features and angiographic assessment of the coronary sinus].
AB  - The endovenous approach for left ventricular lead implantation can be used in
      most patients. A complete angiography of the coronary vein will increase the
      success rate of lead implantation. From a technical point of view, attention
      should be focused on anatomical variation, which leads to a higher number of
      complications like dissection or perforation of the vessel. However, in a number
      of cases a left verticular lead must be implanted epimyocardial due to anatomical
      reasons.

PMID- 16598617
TI  - [Left ventricular pacing and CRT. What CV lead fits into which vein?].
AB  - The experience of 579 patients with left ventricular pacing specific
      characteristics of various leads and lead types for left ventricular stimulation
      are reported. After describing the advantages of coronary vein (CV) leads versus
      epicardial lead usage for left ventricular stimulation, commercially available CV
      leads are introduced and discussed. Since there is no universally applicable CV
      lead, the individual optimal lead choice and the sequelae of erroneous lead
      choice are described in typical clinical examples.

PMID- 16598619
TI  - [Three-dimensional vectorcardiography to predict CRT-responder].
AB  - Cardiac resynchronization therapy (CRT) is an accepted treatment for congestive
      heart failure (NYHA III-IV), but a substantial number of patients show no
      response to therapy. LBB, QRS width and echocardiographic measurements are
      parameters for indication, but they are not valid to predict hemodynamic
      response. A new method based on vector ECG analysis can deliver additional
      information, such as: parts or areas with late excitation, and with slow or fast
      depolarization speed. Electrical excitation is a prerequisite for contraction;
      this leads to the hypothesis that areas with late electrical activation will
      contract later. Algorithms for analysis of the vector ECG (determination of the
      vector -- time, area and speed) may help to identify responders and non
      responders.

PMID- 16598618
TI  - [Strategies to avoid complications and to solve technical problems during the
      implantation of CRT and CRT-D systems].
AB  - Cardiac resynchronization with or without antitachycardiac treatment is now an
      established option to improve the functional status, morbidity and mortality of
      patients with severe symptomatic systolic heart failure, ventricular conduction
      delay and asynchrony. Increasing implant numbers are to be expected. The
      transvenous left ventricular lateral lead placement can now be achieved in up to
      97% of patients. But due to the coronary venous anatomy it may still constitute a
      challenge even for experienced pacemaker and ICD implanters. In addition, it
      confers a considerable risk for complications like coronary sinus dissection and
      perforation, diaphragmatic stimulation and lead dislodgement. An overview is
      given on possible technical problems, solutions, complications and preventive
      strategies.

PMID- 16598620
TI  - [Left ventricular electromechanical latency period is an additional indicator to
      upgrade from right to biventricular DDD pacing].
AB  - In DDD pacing, the left-ventricular electromechanical latency period defines the
      duration between premature ventricular stimulation and the prematurely ending
      left-atrial contribution to left-ventricular filling. It has to be considered in
      diastolic AV delay optimization. Individual duration of this parameter seemed to
      reflect the ventricular function. Therefore, we compared the left-ventricular
      electromechanical latency period due to right ventricular stimulus with the
      documented ejection fraction of two groups, 33 congestive heart failure patients
      carrying biventricular systems and 13 right ventricular paced bradycardia
      patients. A mean latency period of 168+/-26 ms was found in the heart failure
      patients (ejection fraction: 25+/-5%) which was significantly longer (p=0.0039)
      compared to the bradycardia patients (ejection fraction: 51+/-12%) with a mean
      latency of 119+/-13 ms. Thus, an increasing latency period during right
      ventricular DDD pacing therapy indicates decreasing ejection fraction. A cut-off
      interval of 135 ms allowed the discrimination of 93% of our patients as having an
      individual ejection fraction of either up to 35% or above. Thus, the left
      ventricular electromechanical latency period can be used as an additional
      parameter indicating the necessity to upgrade from right to biventricular DDD
      pacing.

PMID- 16598621
TI  - [Functional capacity as a criterion for patient selection--too poor or too good
      for CRT?].
AB  - The article analyses the status of functional tests used in patient selection for
      cardiac resynchronization therapy (CRT). Based on published randomized trials,
      the NYHA classification, the quality of life score, the 6-minute walk and the
      cardio-pulmonary exercise test (CPX) are reviewed. The NYHA classification is a
      weak and unspecific test and should be used only as a basic consideration in
      patient selection. The 6-minute walk test shows a wide spread of values and high
      dependency on patients' motivation. Patients' functional capacity is measured
      most objectively by the CPX test, which additionally stratifies prognosis. We
      conclude that functional capacity is an important criterion in patient selection
      for CRT. However, primary functional status is of minor importance in estimating
      the expected functional benefit since multiple factors influence the success of
      CRT.

PMID- 16598622
TI  - [Are neurohumoral parameters predictive for the efficacy of cardiac
      resynchronization therapy? The role of natriuretic peptides].
AB  - During recent years, heart failure has been recognized as a complex disease
      involving both hemodynamic abnormalities caused by reduced contractile forces and
      neurohormonal changes characterized by an increase in sympathetic tone and an
      activation of the renin-angiotensin-aldosterone system as well as the endothelial
      pathways. Neurohumoral factors represent the natural response of the individual
      to heart failure. Among them natriuretic peptides, i. e., brain natriuretic
      peptide (BNP) and amino-terminal pro BNP (Nt-proBNP) release have recently been
      shown to be a reliable and rapid marker for diagnosis, optimization of
      pharmacological treatment and risk stratification in heart failure patients. This
      article summarizes important aspects of the release of natriuretic peptides as a
      guide for diagnosis, therapy and prognosis of patients with heart failure and
      cardiac resynchronization therapy.

PMID- 16598623
TI  - [Is standard-echocardiography sufficient for identification of responders?].
AB  - During recent years cardiac re-synchronization has become an important tool in
      the treatment of patients with signs and symptoms of heart failure and de
      synchronized contraction of the heart. This article describes the
      pathophysiological basis of de-synchronized contraction due to left bundle branch
      block and the use of conventional echocardiography to unmask whether the
      electrical abnormality is accompanied by an asynchronous contraction in the
      individual patient. The altered contraction in the de-synchronized heart is
      analysed on different levels: atrioventricular dyssynchrony describes the
      disturbed mechanical coupling of the ventricles and atria, interventricular
      dyssynchrony describes the disturbed mechanical coupling of the left and right
      ventricle, and intraventricular dyssynchrony describes the uncoordinated
      contraction of the left ventricle. Since tissue Doppler imaging is implemented
      only in the top level echo machines of the respective manufacturers, this article
      uses parameters derived from standard echo techniques to analyse the different
      aspects of dyssynchrony.

PMID- 16598624
TI  - [Echocardiographic evaluation to select patients for cardiac resynchronization
      therapy].
AB  - Wide QRS complex and asynchronous myocardial contraction in heart failure are
      associated with poor prognosis. Resynchronization can be achieved by
      biventricular pacing (BVP), which leads to hemodynamic and clinical improvement
      and reverse remodeling, and may improve survival. However, there is a substantial
      subset of patients with wide QRS complexes in the electrocardiogram who does not
      improve despite BVP, and there are findings which suggest that resynchronization
      therapy may be also beneficial for heart failure patients with normal QRS
      duration. QRS width predicts the benefit of BVP only with limitation and only
      correlates weakly with echocardiographically determined myocardial asynchrony.
      Determination of asynchrony by tissue Doppler echocardiography seems to be the
      best predictor for improvement after BVP, although no consensus on the optimal
      method to assess asynchrony has yet been achieved. To date, most studies
      evaluating tissue Doppler echo in BVP were performed retrospectively and only one
      prospective study with patient selection for BVP according to echocardiography
      and electrocardiography criteria of asynchrony has been published. These new
      echocardiographic tools will help to prospectively select patients for BVP, help
      to guide implantation and to optimize device programming.

PMID- 16598625
TI  - [From guiding catheter to coronary sinus lead].
AB  - Biventricular pacing system implantation is a challenging procedure. The first
      choice technique to initiate left ventricular pacing consists of a transvenous
      approach via the coronary sinus (CS) tributaries. Different techniques to achieve
      CS access using dedicated guiding catheters and left ventricular leads are
      described. New developments in catheter and lead technology are presented. The
      most common procedure-related complications are reported.

PMID- 16598626
TI  - Echocardiography-based optimization of cardiac resynchronization therapy in
      patients with congestive heart failure and conduction disorders.
AB  - Resynchronization of segmental left ventricular mechanics as well as re
      coordination of both atrio-ventricular and inter-ventricular contraction are
      potential mechanisms responsible for the clinical benefit observed in patients
      with advanced congestive heart failure treated by cardiac resynchronization
      therapy (CRT). Initially electrical conduction problems, in the majority of cases
      a left bundle branch block (LBBB), were considered the target for CRT. However,
      growing experience with CRT in different patient populations including those with
      milder degrees of conduction disturbance, and improved cardiac imaging utilizing
      the tissue Doppler approach, have shown the complexity of CRT and the usefulness
      of sophisticated echocardiographic imaging techniques for therapeutic decision
      making and optimization of CRT device settings.

PMID- 16598627
TI  - [Indication for cardiac resynchronization therapy: Consensus 2005].
AB  - The indication for cardiac resynchronization therapy (CRT) using biventricular
      pacing or ICD systems has to be highly differentiated to optimize the proportion
      of patients who derive significant symptomatic benefit from this therapy, on the
      one hand, and to avoid this invasive treatment in patients with a low probability
      of clinical success of CRT, on the other hand. As a consensus in 2005, it can be
      put forward that there is sufficient evidence for an indication for CRT from
      clinical studies for the following characteristics: 1) Heart failure in NYHA
      functional class III or IV (if cardiac recompensation to class III is at least
      temporarily successful), 2) left ventricular ejection fraction < or =35%, 3) QRS
      duration >130 ms, particularly if left bundle branch block is present, 4) sinus
      rhythm. In addition, available data also suggest an indication for CRT in
      patients with atrial fibrillation if the other criteria listed above are met. The
      indication for CRT is unclear in patients with other intraventricular conduction
      delay (particularly right bundle branch block) while patients with left bundle
      branch block and a QRS duration of 120-130 ms seem to benefit if
      echocardiographic criteria demonstrate ventricular dyssynchrony. Since a
      multiplicity of echocardiographic criteria of ventricular dyssynchrony exists
      which is neither standardized nor evaluated in large-scale randomized trials,
      ventricular dyssynchrony on echocardiography alone cannot be regarded as an
      established indication for CRT without a QRS complex > or =120 ms. Similarly,
      whether heart failure in functional state NYHA II should be regarded as a CRT
      indication is currently being investigated in the randomized RAFT and MADIT-CRT
      trials.

PMID- 16598628
TI  - Percutaneous transvenous mitral commissurotomy in patients with severe mitral
      stenosis and acute rheumatic fever.
AB  - There is a concern that percutaneous transvenous mitral commissurotomy (PTMC)
      performed during acute rheumatic fever (ARF) may result in adverse outcomes. We
      performed a retrospective study at a tertiary care center. Ten patients (ages 8
      12 years) with severe symptomatic mitral stenosis and ARF who underwent PTMC (ARF
      group) were compared with 10 controls with similar mitral valve area (MVA). The
      procedure was successful in all patients. The median MVA increased from 0.7 to
      1.5 cm2 following PTMC in the ARF group and from 0.7 to 1.8 cm2 in the control
      group [p = not significant (NS)]. The median MVA was 1.2 cm2 in the study group
      compared to 1.6 cm2 in the control group (p = 0.02) over a mean follow-up of 17.5
      +/- 11.7 months. Echocardiographic restenosis occurred in 4 patients (40%) in the
      ARF group compared to 1 patient (10%) in the control group (p = NS). The
      improvement in the New York Heart Association functional class was maintained in
      8 patients of the ARF group and 9 patients of the control group. PTMC can be
      performed in children with ARF without an increase in procedural complications.
      However, the restenosis rates appear to be higher.

PMID- 16598629
TI  - An endolithic microbial community in dolomite rock in central Switzerland:
      characterization by reflection spectroscopy, pigment analyses, scanning electron
      microscopy, and laser scanning microscopy.
AB  - A community of endolithic microorganisms dominated by phototrophs was found as a
      distinct band a few millimeters below the surface of bare exposed dolomite rocks
      in the Piora Valley in the Alps. Using in situ reflectance spectroscopy, we
      detected chlorophyll a (Chl a), phycobilins, carotenoids, and an unknown type of
      bacteriochlorophyll-like pigment absorbing in vivo at about 720 nm. In cross
      sections, the data indicated a defined distribution of different groups of
      organisms perpendicular to the rock surface. High-performance liquid
      chromatography analyses of pigments extracted with organic solvents confirmed the
      presence of two types of bacteriochlorophylls besides chlorophylls and various
      carotenoids. Spherical organisms of varying sizes and small filaments were
      observed in situ with scanning electron microscopy and confocal laser scanning
      microscopy (one- and two-photon technique). The latter allowed visualization of
      the distribution of phototrophic microorganisms by the autofluorescence of their
      pigments within the rock. Coccoid cyanobacteria of various sizes predominated
      over filamentous ones. Application of fluorescence-labeled lectins demonstrated
      that most cyanobacteria were embedded in an exopolymeric matrix. Nucleic acid
      stains revealed a wide distribution of small heterotrophs. Some biological
      structures emitting a green autofluorescence remain to be identified.

PMID- 16598630
TI  - Inoculation effects of Pseudomonas putida, Gluconacetobacter azotocaptans, and
      Azospirillum lipoferum on corn plant growth under greenhouse conditions.
AB  - Alcohol production from corn is gaining importance in Ontario, Canada, and
      elsewhere. A major cost of corn production is the cost of chemical fertilizers
      and these continue to increase in price. The competitiveness of alcohol with
      fossil fuels depends on access to low-cost corn that allows growers to earn a
      sustainable income. In this study we set out to determine if we can identify root
      associated microorganisms from Ontario-grown corn that can enhance the nutrient
      flow to corn roots, directly or indirectly, and help minimize the use of
      extraneous fertilizer. Bacteria were isolated from corn rhizosphere and screened
      for their capacity to enhance corn growth. The bacteria were examined for their
      ability to fix nitrogen, solubilize phosphate, and produce indole acetic acid
      (IAA) and antifungal substances on potato dextrose agar. Bacterial suspensions
      were applied to pregerminated seed of four corn varieties (39D82, 39H84, 39M27,
      and 39T68) planted in sterilized sand and unsterilized cornfield soil. The plants
      were grown under greenhouse conditions for 30 days. Three isolates were
      identified as having growth-promoting effect. These bacteria were identified as
      to species by biochemical tests, fatty acid profiles, and 16S rDNA sequence
      analysis. Corn rhizosphere isolates, Gluconacetobacter azotocaptans DS1,
      Pseudomonas putida CQ179, and Azospirillum lipoferum N7, provided significant
      plant growth promotion expressed as increased root/shoot weight when compared to
      uninoculated plants, in sand and/or soil. All strains except P. putida CQ179 were
      capable of nitrogen fixation and IAA production. Azospirillum brasilense,
      however, produced significantly more IAA than the other isolates. Although
      several of the strains were also able to solubilize phosphate and produce
      metabolites inhibitory to various fungal pathogens, these properties are not
      considered as contributing to growth promotion under the conditions used in this
      study. These bacteria will undergo field tests for their effect on corn growth.

PMID- 16598631
TI  - 16S rDNA-based analysis of dominant bacterial populations associated with early
      life stages of coho salmon (Oncorhynchus kisutch).
AB  - In this study, we used a 16S rDNA-based approach to determine bacterial
      populations associated with coho salmon (Oncorhynchus kisutch) in its early life
      stages, highlighting dominant bacteria in the gastrointestinal tract during
      growth in freshwater. The present article is the first molecular analysis of
      bacterial communities of coho salmon. Cultivability of the salmon
      gastrointestinal microbiota was estimated by comparison of direct microscopic
      counts (using acridine orange) with colony counts (in tryptone soy agar). In
      general, a low fraction (about 1%) of the microbiota could be recovered as
      cultivable bacteria. Using DNA extracted directly from individuals belonging to
      the same lot, bacterial communities present in eggs and gastrointestinal tract of
      first-feeding fries and juveniles were monitored by polymerase chain reaction
      denaturing gradient gel electrophoresis (PCR-DGGE). The DGGE profiles revealed
      simple communities in all stages and exposed changes in bacterial community
      during growth. Sequencing and phylogenetic analysis of excised DGGE bands
      revealed the nature of the main bacteria found in each stage. In eggs, the
      dominant bacteria belonged to beta-Proteobacteria (Janthinobacterium and
      Rhodoferax). During the first feeding stage, the most abundant bacteria in the
      gastrointestinal tract clustered with gamma-Proteobacteria (Shewanella and
      Aeromonas). In juveniles ranging from 2 to 15 g, prevailing bacteria were
      Pseudomonas and Aeromonas. To determine the putative origin of dominant
      Pseudomonas and Aeromonas found in juvenile gastrointestinal tracts, primers for
      these groups were designed based on sequences retrieved from DGGE gel.
      Subsequently, samples of the water influent, pelletized feed, and eggs were
      analyzed by PCR amplification. Only those amplicons obtained from samples of eggs
      and the water influent presented identical sequences to the dominant bands of
      DGGE. Overall, our results suggest that a stable microbiota is established after
      the first feeding stages and its major components could be derived from water and
      egg epibiota.

PMID- 16598632
TI  - Closely related Wolbachia strains within the pumpkin arthropod community and the
      potential for horizontal transmission via the plant.
AB  - Phylogenetic studies have implicated frequent horizontal transmission of
      Wolbachia among arthropod host lineages. However, the ecological routes for such
      lateral transfer are poorly known. We surveyed the species of two arthropod
      communities, one on pumpkin and the other on loofah plants, for Wolbachia,
      constructed wsp gene phylogenies of those Wolbachia strains found to infect
      community members, and established ecological links among infected members. Four
      taxonomically diverse insects in the pumpkin arthropod community contained very
      closely related Wolbachia wsp sequences (<1.5% divergence by Kimura-2-parameter
      distances). These insects, namely, the whitefly Bemisia tabaci, the planthopper
      Nisia nervosa, the flea beetle Phyllotreta sp., and the fleahopper Halticus
      minutus, were all collected from pumpkin leaves. They were ecologically linked
      through feeding on the same leaf substrate. Unlike other infected leaf insects,
      the whitefly population appeared to have a permanent breeding relationship with
      pumpkin plants, and high and stable, but not fixed, monthly Wolbachia infection
      rates. Our findings suggest potential roles for the plant in Wolbachia
      transmission and for whiteflies in being an infection source for other pumpkin
      leaf-feeding insects.

PMID- 16598633
TI  - Tetracyclines and tetracycline resistance in agricultural soils: microcosm and
      field studies.
AB  - The influence of the use of antibiotics on the prevalence of resistance genes in
      the environment is still poorly understood. We studied the diversity of
      tetracycline and sulfonamide resistance genes as influenced by fertilization with
      pig manure in soil microcosms and at two field locations. Manure contained a high
      diversity of resistance genes, regardless of whether it stemmed from a farm
      operation with low or regular use of antibiotics. In the microcosm soils, the
      influence of fertilization with manure was clearly shown by an increase in the
      number of resistance genes in the soil after manuring. Spiking of the
      tetracycline compounds to the microcosms had only little additional impact on the
      diversity of resistance genes. Overall, the tetracycline resistance genes tet(T),
      tet(W), and tet(Z) were ubiquitous in soil and pig slurries, whereas tet(Y),
      tet(S), tet(C), tet(Q), and tet(H) were introduced to the microcosm soil by
      manuring. The diversity of tetracycline and sulfonamide [sul(1), sul(2), and
      sul(3)] resistance genes on a Swiss pasture was very high even before slurry
      amendment, although manure from intensive farming had not been applied in the
      previous years. The additional effect of manuring was small, with the
      tetracycline and sulfonamide resistance diversity staying at high levels for the
      complete growth season. At an agricultural field site in Germany, the diversity
      of tetracycline and sulfonamide resistance genes was considerably lower, possibly
      reflecting regional differences in gene diversity. This study shows that there is
      a considerable pool of resistance genes in soils. Although it is not possible to
      conclude whether this diversity is caused by the global spread of resistance
      genes after 50 years of tetracycline use or is due to the natural background in
      soil resistance genes, it highlights a role that environmental reservoirs might
      play in resistance gene capture.

PMID- 16598634
TI  - Relationships between microbial community structure and soil processes under
      elevated atmospheric carbon dioxide.
AB  - There is little current understanding of the relationship between soil microbial
      community composition and soil processes rates, nor of the effect climate change
      and elevated CO(2) will have on microbial communities and their functioning.
      Using the eastern cottonwood (Populus deltoides) plantation at the Biosphere 2
      Laboratory, we studied the relationships between microbial community structure
      and process rates, and the effects of elevated atmospheric CO(2) on microbial
      biomass, activity, and community structure. Soils were sampled from three
      treatments (400, 800, and 1200 ppm CO(2)), a variety of microbial biomass and
      activity parameters were measured, and the bacterial community was described by
      16S rRNA libraries. Glucose substrate-induced respiration (SIR) was significantly
      higher in the 1200 ppm CO(2) treatment. There were also a variety of complex,
      nonlinear responses to elevated CO(2). There was no consistent effect of elevated
      CO(2) on bacterial diversity; however, there was extensive variation in microbial
      community structure within the plantation. The southern ends of the 800 and 1200
      ppm CO(2) bays were dominated by beta-Proteobacteria, and had higher fungal
      biomass, whereas the other areas contained more alpha-Proteobacteria and
      Acidobacteria. A number of soil process rates, including salicylate, glutamate,
      and glycine substrate-induced respiration and proteolysis, were significantly
      related to the relative abundance of the three most frequent bacterial taxa, and
      to fungal biomass. Overall, variation in microbial activity was better explained
      by microbial community composition than by CO(2) treatment. However, the altered
      diversity and activity in the southern bays of the two high CO(2) treatments
      could indicate an interaction between CO(2) and light.

PMID- 16598635
TI  - Feeding characteristics of an amoeba (Lobosea: Naegleria) grazing upon
      cyanobacteria: food selection, ingestion and digestion progress.
AB  - Bacterivory by heterotrophic nanoflagellates and ciliates has been widely studied
      in aquatic environments, but data on the grazing of amoebae, are still scarce.
      From the water samples of Dianchi Lake (Kunming, Yunnan Province, China), we
      isolated an amoeba, designated as Naegleria sp. strain W2, which had potent
      grazing effects on some kind of cyanobacteria. The food selection mechanism and
      the digestion process of the amoeba were investigated in batch experiments.
      Predation experiments showed that filamentous cyanobacteria (e.g., Anabaena,
      Cylindrospermum, Gloeotrichia, and Phormidium) were readily consumed, with
      clearance rates ranging from 0.332 to 0.513 nL amoeba(-1) h(-1). The tight
      threads (Oscilltoria) and aggregates (Aphanizomenon) could not be ingested;
      however, their sonicated fragments were observed inside food vacuoles, suggesting
      that their morphologies prevent them from being ingested. Live video microscopy
      noted that unicellular Chroococcaceae (e.g., Synechococcus, Aphanocapsa, and
      Microcystis) were excreted after ingestion, indicating that food selection takes
      place inside food vacuoles. To determine whether the tastes or the toxins
      prevented them from being digested, heat-killed cells were retested for
      predation. Digestion rates and ingestion rates of the amoebae for filamentous
      cyanobacteria were estimated from food vacuole content volume. Through a "cold
      chase" method, we found that the food vacuole contents declined exponentially in
      diluted amoebae cells, and digestion rates were relatively constant, averaging
      about 1.5% food vacuole content min(-1) at 28 degrees Celsius. Ingestion strongly
      depended on the satiation status of the amoebae, starved amoebae fed at higher
      rates compared with satiated amoebae. Our results suggest that the food selection
      and food processing mechanisms of the amoeba are similar to those of interception
      feeding flagellates; however, filamentous cyanobacteria cannot obtain a refuge
      under the grazing pressure of phagotrophic amoebae, which may widen our knowledge
      on the grazing of protists.

PMID- 16598636
TI  - Ecological physiology of a coral pathogen and the coral reef environment.
AB  - Laboratory studies on the ecological physiology of a coral pathogen were carried
      out to investigate growth potential in terms of environmental factors that may
      control coral diseases on reefs. The disease chosen for this study, white plague
      type II, is considered to be one of the major diseases of Caribbean scleractinian
      corals, affecting a wide range of coral hosts and causing rapid and widespread
      tissue loss. It is caused by a single pathogen, the bacterium Aurantimonas
      coralicida. A series of laboratory experiments using a pure culture of the
      pathogen was carried out to examine the roles of temperature, pH, and O(2)
      concentration on growth rate. Results revealed optimal growth between 30 and 35
      degrees Celsius, and between pH values of 6 and 8. There was a distinctive
      synergistic relationship between pH and temperature. Increasing temperature from
      25 to 35 degrees Celsius expanded the range of pH tolerance from a minimum of 6.0
      down to 5.0. O(2) concentration directly affected growth rate, which increased
      with increasing O(2). The combined effects of increasing O(2) and increasing
      temperature resulted in a synergistic effect of more rapid growth. These
      laboratory results are discussed in terms of the coral host and the range of the
      environmental factors that occur on coral reefs. We conclude that changing
      environmental conditions in the reef environment, in particular observed
      increases in water temperature, may be promoting coral diseases by allowing coral
      pathogens to expand their ecological niches. In the case of the white plague type
      II pathogen, elevated temperature would allow A. coralicida to colonize the low
      pH environment of the coral surface mucopolysaccharide layer as an initial stage
      of infection. The synergistic effect between temperature and oxygen concentration
      appeared to be less environmentally relevant for this coral pathogen.

PMID- 16598637
TI  - The response of Vibrio- and Rhodobacter-related populations of the NW
      Mediterranean Sea to additions of dissolved organic matter, phages, or dilution.
AB  - We investigated the growth response of the heterotrophic prokaryotic community
      focusing on Vibrio- and Rhodobacter-related populations (SRF3) to variation in
      the availability of dissolved organic matter (DOM), population density-dependent
      effects, and prokaryotic virus (phage) infection in coastal and offshore waters
      of the NW Mediterranean Sea. We tested the response of the prokaryotic community
      to three different DOM fractions prepared by ultrafiltration. One of the DOM
      fractions contained phages (<0.2 m), a second was virus-free (<100 kDa), and a
      third contained only low molecular weight (<1 kDa). The proportion of Vibrio and
      SRF3 populations as determined by fluorescent in situ hybridization in the
      community ranged from <1 to 6.2% and from 3.2 to 6.3%, respectively. Based on
      changes in cell numbers, growth rates ranged from 2.1 to 3.1 day(-1) for Vibrio
      and from 0.8 to 1.2 day(-1) for SRF3. Growth rates of Vibrio were similar or
      higher than those of the total prokaryotic community, whereas the ability of
      Vibrio to use high molecular weight (HMW) DOM and the responses to additions of
      phage-rich material were lower. Growth rates of SRF3 were lower than that of the
      community. Susceptibility to infection of SRF3 was sometimes lower than in the
      community, whereas the growth stimulation of HMW DOM was similar or lower.
      Reducing the cell concentrations of the prokaryotic community by dilution
      stimulated the overall growth of the community, including that of its constituent
      Vibrio and SRF3 populations, but the effect was smaller on the SRF3 and greater
      on Vibrio populations than for the total community. Comparisons with the
      community also revealed that life strategy traits of bacterial populations
      differed between coastal and offshore waters. Overall, our data suggest that
      Vibrio is an r-strategist or opportunistic population in the NW Mediterranean
      Sea, whereas SRF3 is a K-strategist or equilibrium population.

PMID- 16598638
TI  - Culturability of stream bacteria assessed at the assemblage and population
      levels.
AB  - Lotic bacterial communities can be examined at multiple levels: from the
      assemblage level to populations of individual species. In stream environments, as
      in many other systems, the percentage of bacteria that are culturable is quite
      low. In this study, the culturability of the overall bacterial assemblage, as
      well as the culturability of three common species (Acinetobacter calcoaceticus,
      Burkholderia cepacia, and Pseudomonas putida), was determined in samples
      collected from four streams on three dates. Colony hybridization (colonies were
      grown on modified nutrient agar) and fluorescent in situ hybridization were used
      to calculate the percentage of cells of a given species that were culturable.
      Approximately half of the overall assemblage was estimated to be viable but
      nonculturable cells (VBNC). The culturability of two of the species was low
      (0.29% for A. calcoaceticus and 0.46% for P. putida), whereas the value for B.
      cepacia (2.48%) exceeded the overall assemblage level culturability (0.90%).
      Overall, both bacterial assemblages and populations were dominated by VBNC. These
      results show quantitatively that not all members of a species that has culturable
      representatives are culturable when retrieved from natural populations, likely
      because of interspecific phenotypic and genotypic variability. Thus, the large
      pool of nonculturable cells includes representatives of species that are, under
      some circumstances, culturable.

PMID- 16598639
TI  - Diverse bacteria associated with root nodules of spontaneous legumes in Tunisia
      and first report for nifH-like gene within the genera Microbacterium and
      Starkeya.
AB  - We characterized 34 endophytic bacterial isolates associated to root nodules
      collected from spontaneous legumes in the arid zone of Tunisia by 16S rDNA
      polymerase chain reaction (PCR)-restriction fragment length polymorphism, whole
      cell protein sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), 16S rDNA and 16S-23S rDNA internal transcribed spacer sequencing.
      Phylogenetically, these isolates belong to the branches containing the genera
      Inquilinus, Bosea, Rhodopseudomonas, Paracraurococcus, Phyllobacterium,
      Ochrobactrum, Starkeya, Sphingomonas, Pseudomonas, Agromyces, Microbacterium,
      Ornithinicoccus, Bacillus, and Paenibacillus. These strains did not induce any
      nodule formation when inoculated on the wide host spectrum legume species M.
      atropurpureum (Siratro) and no nodA gene could be amplified by PCR. However, nifH
      sequences, most similar to those of Sinorhizobium meliloti, were detected within
      strains related to the genera Microbacterium, Agromyces, Starkeya and
      Phyllobacterium.

PMID- 16598641
TI  - A complementary method for the detection of osteoblastic metastases on digitized
      radiographs.
AB  - PURPOSE: This study was conducted to evaluate the diagnostic usefulness of gray
      level parameters in order to distinguish healthy bone from osteoblastic
      metastases on digitized radiographs. MATERIALS AND METHODS: Skeletal radiographs
      of healthy bone (n = 144) and osteoblastic metastases (n = 35) were digitized
      using pixels 0.175 mm in size and 4,096 gray levels. We obtained an optimized
      healthy bone classification to compare with pathological bone: cortical,
      trabecular, and flat bone. The osteoblastic metastases (OM) were classified in
      nonflat and flat bone. These radiological images were analyzed by using a
      computerized method. The parameters (gray scale) calculated were: mean, standard
      deviation, and coefficient of variation (MGL, SDGL, and CVGL, respectively) based
      on gray level histogram analysis. Diagnostic utility was quantified by
      measurement of parameters on healthy and pathological bone, yielding
      quantification of area under the receiver operating characteristic (ROC) curve,
      AUC. RESULTS: All three image parameters showed high and significant values of
      AUC when comparing healthy trabecular bone and nonflat bone OM, showing MGL the
      best discriminatory ability (0.97). As for flat bones, MGL showed no ability to
      distinguish between healthy and flat bone OM (0.50). This could be achieved by
      using SDGL or CVGL, with both showing a similar diagnostic ability (0.85 and
      0.83, respectively). CONCLUSION: Our results show that the use of gray level
      parameters quantify healthy bone and osteoblastic metastases zones on digitized
      radiographs. This may be helpful as a complementary method for differential
      diagnosis. Moreover, our method will allow us to study the evolution of
      osteoblastic metastases under medical treatment.

PMID- 16598640
TI  - Spatial stratification of soil bacterial populations in aggregates of diverse
      soils.
AB  - Most soil microbial community studies to date have focused on homogenized bulk
      soil samples. However, it is likely that many important microbial processes occur
      in spatially segregated microenvironments in the soil leading to a microscale
      biogeography. This study attempts to localize specific microbial populations to
      different fractions or compartments within the soil matrix. Microbial populations
      associated with macroaggregates and inner- versus total-microaggregates of three
      diverse soils were characterized using culture-independent, molecular methods.
      Despite their relative paucity in most surveys of soil diversity, representatives
      of Gemmatimonadetes and Actinobacteria subdivision Rubrobacteridae were found to
      be highly abundant in inner-microaggregates of most soils analyzed. By contrast,
      clones affiliated with Acidobacteria were found to be relatively enriched in
      libraries derived from macroaggregate fractions of nearly all soils, but poorly
      represented in inner-microaggregate fractions. Based upon analysis of 16S rRNA,
      active community members within microaggregates of a Georgian Ultisol were
      comprised largely of Gemmatimonadetes and Rubrobacteridae, while within
      microaggregates of a Nebraska Mollisol, Rubrobacteridae and Alphaproteobacteria
      were the predominant active bacterial lineages. This work suggests that
      microaggregates represent a unique microenvironment that selects for specific
      microbial lineages across disparate soils.

PMID- 16598642
TI  - LONI visualization environment.
AB  - Over the past decade, the use of informatics to solve complex neuroscientific
      problems has increased dramatically. Many of these research endeavors involve
      examining large amounts of imaging, behavioral, genetic, neurobiological, and
      neuropsychiatric data. Superimposing, processing, visualizing, or interpreting
      such a complex cohort of datasets frequently becomes a challenge. We developed a
      new software environment that allows investigators to integrate multimodal
      imaging data, hierarchical brain ontology systems, on-line genetic and phylogenic
      databases, and 3D virtual data reconstruction models. The Laboratory of Neuro
      Imaging visualization environment (LONI Viz) consists of the following
      components: a sectional viewer for imaging data, an interactive 3D display for
      surface and volume rendering of imaging data, a brain ontology viewer, and an
      external database query system. The synchronization of all components according
      to stereotaxic coordinates, region name, hierarchical ontology, and genetic
      labels is achieved via a comprehensive BrainMapper functionality, which directly
      maps between position, structure name, database, and functional connectivity
      information. This environment is freely available, portable, and extensible, and
      may prove very useful for neurobiologists, neurogenetisists, brain mappers, and
      for other clinical, pedagogical, and research endeavors.

PMID- 16598643
TI  - Measurement of Signal-to-Noise and Contrast-to-Noise in the fBIRN Multicenter
      Imaging Study.
AB  - The ability to analyze and merge data across sites, vendors, and field strengths
      depends on one's ability to acquire images with the same image quality including
      image smoothness, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).
      SNR can be used to compare different magnetic resonance scanners as a measure of
      comparability between the systems. This study looks at the SNR and CNR ratios in
      structural fast spin-echo T2-weighted scans acquired in five individuals across
      ten sites that are part of Functional Imaging Research of Schizophrenia Testbed
      Biomedical Informatics Research Network (fBIRN). Different manufacturers, field
      strengths, gradient coils, and RF coils were used at these sites. The SNR of gray
      matter was fairly uniform (41.3-43.3) across scanners at 1.5 T. The higher field
      scanners produced images with significantly higher SNR values (44.5-108.7 at 3 T
      and 50.8 at 4 T). Similar results were obtained for CNR measurements between
      gray/white matter at 1.5 T (9.5-10.2), again increasing at higher fields (10.1
      28.9 at 3 T and 10.9 at 4 T).

PMID- 16598644
TI  - Predicting clinical image delivery time by monitoring PACS queue behavior.
AB  - The expectation of rapid image retrieval from PACS users contributes to increased
      information technology (IT) infrastructure investments to increase performance as
      well as continuing demands upon PACS administrators to respond to "slow" system
      performance. The ability to provide predicted delivery times to a PACS user may
      curb user expectations for "fastest" response especially during peak hours. This,
      in turn, could result in a PACS infrastructure tailored to more realistic
      performance demands. A PACS with a stand-alone architecture under peak load
      typically holds study requests in a queue until the DICOM C-Move command can take
      place. We investigate the contents of a stand-alone architecture PACS
      RetrieveSend queue and identified parameters and behaviors that enable a more
      accurate prediction of delivery time. A prediction algorithm for studies delayed
      in a stand-alone PACS queue can be extendible to other potential bottlenecks such
      as long-term storage archives. Implications of a queue monitor in other PACS
      architectures are also discussed.

PMID- 16598645
TI  - Inhaled nitric oxide improves pulmonary functions following massive pulmonary
      embolism: a report of four patients and review of the literature.
AB  - Acute pulmonary embolism increases pulmonary vascular resistance and may lead to
      acute right ventricular failure and cardiocirculatory collapse and respiratory
      failure, possibly resulting in substantial morbidity and mortality. Inhaled
      nitric oxide (NO) dilates pulmonary blood vessels and has been used to reduce
      pulmonary vascular resistance in patients with chronic thromboembolic pulmonary
      hypertension and acute respiratory distress syndrome. This case series describes
      our experience with inhaled NO administered to four patients suffering from acute
      massive pulmonary embolism following abdominal surgery. The four described
      patients recovering from small bowel resection, pancreatoduodenectomy,
      hemipelvectomy, or recent gastrointestinal bleeding had severe respiratory and
      hemodynamic deterioration due to pulmonary embolism. Each received inhaled NO (20
      25 ppm) via the inspiratory side of the breathing circuit of the ventilator.
      Pulmonary and systemic blood pressures, heart rate, and lung gas exchange
      improved in all the patients within minutes after the initiation of NO
      administration. Inhaled NO may be useful in treating acute massive pulmonary
      embolism. This potential application warrants further investigation.

PMID- 16598646
TI  - Elevated carbon dioxide tension as a predictor of subsequent adverse events in
      infants with bronchopulmonary dysplasia.
AB  - Infants with bronchopulmonary dysplasia (BPD) are at risk for numerous
      complications following discharge from the Neonatal Intensive Care Unit (NICU).
      Few studies have evaluated risk factors for adverse events (AE). This
      retrospective study provided an initial evaluation of the use of capillary carbon
      dioxide (PCO2) tension as a predictor of infants with BPD at increased risk for
      AE. PCO2 was compared in patients who suffered, or avoided, severe AE, defined as
      pulmonary hypertension, death, or subsequent reintubation or tracheostomy for
      respiratory illness. One hundred twelve consecutive patients followed at the BPD
      clinic were evaluated, and data from 104 subjects were suitable for analysis.
      Mean PCO2, obtained shortly before or after discharge from NICU, was 47.2 mmHg
      (range, 31-83). PCO2 was significantly higher in patients who required
      reintubation and ventilation (54.7 vs. 46.7, p < 0.04). No cutoff value of PCO2
      clearly distinguished patients with subsequent AE. PCO2 was not significantly
      higher in the group of patients who had a severe AE than in the group of patients
      who did not have a severe AE, but logistic regression showed a significant
      association between PCO2 and risk of both severe AE (p = 0.018), and readmission
      to hospital (p = 0.038). An elevated PCO2 is associated with an increased risk of
      AE, including reintubation, and readmission to hospital, in infants with BPD.
      Patients with an elevated discharge PCO2 may require closer monitoring during
      followup. Prospective studies will be needed to confirm these observations.

PMID- 16598648
TI  - Role of soluble interleukin-2 receptor levels in patients with latent
      tuberculosis.
AB  - Serum soluble interleukin-2 receptor (sIL-2R) serves as a marker of disease
      activity in patients with tuberculosis (TB). However, little is known about its
      role in latent TB. The aim of this study was to assess the levels of sIL-2R in
      patients with latent TB and correlate them with the purified protein derivate
      (PPD) test results. Patients with a diagnosis of latent TB were divided into
      three subgroups by induration size: <10 mm, 10-20 mm, >20 mm. Blood was collected
      for sIL-2R assay. Findings were compared to a healthy control group. The study
      group consisted of 44 patients (68% male) of mean ( +/- SD) age 20 +/- 10 years,
      and the control group consisted of 41 subjects (42% male) aged 31 +/- 11 years.
      Comparison of the two groups yielded a significantly higher serum sIL-2R level in
      the patients (450 +/- 224 U/ml vs. 374 +/- 30 U/ml, p = 0.03). Mean sIL-2R levels
      were significantly correlated with the presence of latent TB (p = 0.03), and with
      purified protein derivative (PPD) subgroups: 387 +/- 177 U/ml for induration size
      <10 mm, NS; 450 +/- 238 U/ml for 10-20 mm, p = 0.04, and 605 +/- 235 U/ml for >20
      mm, p < 0.0001. sIL-2R assay may serve as an additional tool to estimate the
      extent of the immune response in patients with latent TB.

PMID- 16598647
TI  - Matrix metalloproteinase-1 activation via plasmin generated on alveolar
      epithelial cell surfaces.
AB  - Plasmin is a potent protease related to tissue repair/remodeling not by
      fibrinolysis alone but also by activation of cytokines such as transforming
      growth factor and hepatocyte growth factor and by activation of matrix
      metalloproteases. We examined whether matrix matalloproteinase-1 was activated
      via plasminogen activation on surfaces of cultured alveolar epithelial cells (A
      549). Cells were cultured overnight with plasminogen, pro-matrix
      metalloproteinase-1, and type I collagen as a substrate. Sodium dodecil sulfate
      polyacrylamide gel electrophoresis was used to detect type I collagen degradation
      in culture supernatant. Collagen degradation corresponded to cell surface plasmin
      generation. No such finding was seen in the absence of cells or plasminogen.
      Alveolar epithelial plasminogen activation is important in matrix
      metalloproteinase-1 activation and thus presumably in tissue remodeling in
      pulmonary fibrosing pulmonary diseases such as idiopathic pulmonary fibrosis.

PMID- 16598649
TI  - Lung microvascular endothelial cell injury caused by treatment with
      polymorphonuclear neutrophils and low-IgM serum: a model of transfusion-related
      acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is one of the serious side effects
      that occur immediately after blood transfusion. The etiology of TRALI may be
      attributed to the presence of anti-human leukocyte antigen (HLA) and/or anti
      polymorphonuclear neutrophil (PMN) antibodies in the plasma of donor blood
      products. However, the precise mechanisms underlying the development of TRALI are
      unclear to date. To further evaluate mechanisms we investigated the relationship
      between human lung microvascular endothelial cell (LME cell) lysis and normal
      human serum. We found the LME cell lysis occurred within 4 h of combining LME
      cells with PMNs and low-IgM serum, but not with high-IgM serum, without serum, or
      with PMNs alone. By flow cytometry and modified ELISA, the specific binding of
      not only PMN surface proteins but also intact PMNs to LME cells was observed in
      the presence of low-IgM serum but not in the presence of high-IgM serum or in the
      absence of serum. The blocking of CD7 expressed on LME cells or the blocking of
      CD16 or CD32 on PMNs by pretreatment with monoclonal antibodies (mAbs) inhibited
      LME cell lysis. Moreover, two serum samples with low lgM obtained from blood
      donors whose sera contained anti-PMN antibodies caused LME cell lysis in the
      presence of PMNs. Furthermore, the addition of an elastase inhibitor inhibited
      the lysis of LME cells caused by the treatment with PMNs and low-IgM serum. Our
      present results suggest that PMNs and low-IgM serum are the likely components in
      the development of TRALI.

PMID- 16598650
TI  - Role of extracellular signal-regulated kinase, p38 kinase, and activator protein
      1 in transforming growth factor-beta1-induced alpha smooth muscle actin
      expression in human fetal lung fibroblasts in vitro.
AB  - Myofibroblasts characterized by alpha smooth muscle actin(alpha-SMA) expression
      play a key role in pulmonary fibrosis. Transforming growth factor-beta1 (TGF
      beta1) is likely to be involved in the emergence of myofibroblasts, but the
      intracellular signal pathways for this process have not been well determined. The
      aim of the present study was to investigate the role of mitogen-activated protein
      kinase (MAPK)/activator protein-1 (AP-1) signaling pathways in TGF-beta1-induced
      alpha-SMA expression in human fetal lung fibroblasts (HLF-02). We found that TGF
      beta1 treatment activated p38 kinase and extracellular signal-regulated kinase
      (Erk) in HLF-02 cells. The induction of alpha-SMA by TGF-beta1 was suppressed by
      p38 kinase inhibitor (SB203580) and Erk inhibitor (PD98059). AP-1 inhibitor
      curcumin also inhibited TGF-beta1-induced alpha-SMA expression. In addition,
      dominant negative mutant c-Jun (TAM67) downregulated TGF-beta1-induced AP-1
      transactivation and alpha-SMA expression. In additional, PD98059 but not SB203580
      inhibited the AP-1 DNA binding activity induced by TGF-beta1. Based on these
      findings, we conclude that p38 kinase, Erk, and AP-1 are responsible for the
      alpha-SMA expression induced by TGF-beta1 in human fetal lung fibroblasts. Erk is
      involved in inducing alpha-SMA expression via AP-1 activation.

PMID- 16598651
TI  - Sleep-disordered breathing in nondialyzed patients with chronic renal failure.
AB  - The prevalence and significance of sleep-disordered breathing (SDB) in dialysis
      independent chronic renal failure (CRF) remains unknown. We studied the presence
      of SDB in nondialyzed CRF patients. Diagnostic polysomnography was performed in
      consecutive stable nondialyzed CRF patients. Inclusion criteria were age <or=70
      years, absence of systolic dysfunction or history of pulmonary edema, FEV(1) >
      70% pr, absence of neurologic disease or hypothyroidism, and calculated
      creatinine clearance <40 ml/min. Thirty-five patients (19 male, 16 female) were
      studied. An apnea-hypopnea index (AHI) >or=5/h was present in 54.3% (almost
      exclusively obstructive events). AHI correlated with urea (r = 0.35, p = 0.037),
      age (r = 0.379, p = 0.025), and body mass index (BMI) (r = 0.351, p = 0.038), but
      not with creatinine clearance. AHI or SDB were unrelated to gender. In
      nondiabetics (n = 25), AHI correlated with urea (r = 0.608, p = 0.001) and
      creatinine clearance (r = -0.50, p = 0.012). Nondiabetics with severe CRF
      (calculated GFR < 15 ml/min/1.73 m(2)) had a significantly higher AHI compared
      with less severe CRF. Restless legs syndrome (RLS) was present in 37.1% and
      periodic limb movements in 28.6%. Daytime sleepiness was not associated with
      respiratory events, but was more common in patients with RLS. The prevalence of
      SDB and RLS is high in dialysis-independent CRF. SDB weakly correlates with
      indices of kidney function and this association becomes stronger in nondiabetics.

PMID- 16598652
TI  - The inhibitory effects of coumarin on the germination of durum wheat (Triticum
      turgidum ssp. durum, cv. Simeto) seeds.
AB  - The event chain leading to germination blockage in durum wheat (Triticum turgidum
      ssp. durum Desf.) seeds exposed to the allelochemical coumarin (2H-chromen-2-one)
      was studied. The physiological and biochemical aspects thought to be critical for
      a successful seed germination were measured. At concentrations above 200 microM:
      , coumarin inhibited seed germination in a concentration-dependent manner.
      Inhibition occurred early during seed imbibition (phase I), was rapid, and
      irreversible. During phase I, coumarin inhibited water uptake, electrolyte
      retention capacity, and O(2) consumption. Later on, coumarin delayed the
      reactivation of peroxidases, enhanced the activity of superoxide dismutase,
      decreased the activities of selected marker enzymes for metabolic resumption, and
      repressed the transcription of molecular chaperones involved in secretory
      pathways. Insufficient and/or late seed rehydration caused by coumarin could have
      delayed membrane stabilization or decreased respiratory O(2) consumption, both of
      which are conducive to an overproduction of reactive O(2) species. Being
      unbalanced by an adequate upsurge of antioxidant defense systems, the resulting
      oxidative stress might have ultimately interfered with the germination program.

PMID- 16598653
TI  - (Z)-9-nonacosene-major component of the contact sex pheromone of the beetle
      Megacyllene caryae.
AB  - Male Megacyllene caryae (Gahan) (Coleoptera: Cerambycidae) respond to females
      only after touching them with their antennae, indicating that mate recognition is
      mediated by a contact sex pheromone. Gas chromatography-mass spectrometry
      analyses of whole-body solvent extracts of male and female M. caryae revealed
      substantial differences in hydrocarbon profiles, with nearly half of the
      compounds in the extracts from females being absent from those of males.
      Biological activities of fractions of crude extracts of females, and
      reconstructed blends of the most abundant straight-chain (nC(27), nC(28),
      nC(29)), methyl-branched (2Me-C(26), 9Me-C(29), 11, 13, 15Me-C(29)), and
      unsaturated (Z9:C(29), Z13:C(29), Z14:C(29), Z13:C(31), Z14:C(31), Z15:C(31))
      compounds in extracts of females were tested in arena bioassays, assessing four
      steps in the mating behavior sequence of males (orientation, arrestment, body
      alignment, mounting and attempting to couple the genitalia). Males showed limited
      response to dead females treated with fractions of the crude extract or blends of
      synthetic straight-chain and methyl-branched alkanes, but responded strongly to
      the blend of synthetic monoenes. Further trials determined that the complete
      sequence of mating behaviors, up to and including coupling the genitalia, was
      elicited by Z9:C(29) alone. Z9:C(29) is a homolog of the contact pheromone
      (Z9:C(25)) of the congener M. robiniae (Forster). Previous work with M. robiniae
      suggested that wipe sampling of cuticular hydrocarbons of females by solid phase
      microextraction yielded a more representative profile of components actually
      encountered by a male's antennae, and so provided a more readily interpretable
      profile of potential semiochemicals present in the wax layer than does solvent
      extraction. We tested this hypothesis by comparing hydrocarbon profiles of female
      M. caryae by the two sampling methods. Z9:C(29) was the only compound among the
      dominant hydrocarbons that was present in higher abundance in SPME than in
      solvent extracts ( approximately 12% vs. approximately 8%, respectively),
      supporting this hypothesis.

PMID- 16598654
TI  - Correlating material properties with tissue composition in enzymatically digested
      bovine annulus fibrosus and nucleus pulposus tissue.
AB  - Aging and degeneration of the intervertebral disk are accompanied by decreases in
      water and proteoglycan contents, and structural alterations. The aim of this
      study was to determine the impact of compositional changes on the material
      properties of intervertebral disk tissues. Confined compression stress-relaxation
      experiments were applied to bovine caudal annulus fibrosus and nucleus pulposus
      tissue specimens that were separated into three experimental groups: in situ,
      free-swelling control (PBS), and digestion (chondroitinase-ABC). Measurements of
      glycosaminoglycan (GAG) and water content, as well as nonlinear finite
      deformation biphasic theory and multiple linear regression analyses were
      performed. The compressive modulus HA0 and permeability k0 of in situ specimens
      were 0.37+/-0.06 MPa and 0.49+/-0.08x10(-15) m4 N-1 s-1 for nucleus, and 0.74+/
      0.13 MPa and 0.42+/-0.05x10(-15) m4 N-1 s-1 for annulus, respectively. There was
      a larger effect of swelling and digestion on the material properties and
      biochemical composition of nucleus pulposus than for annulus fibrosus.
      Alterations in proteoglycan and water content affected the compressive modulus
      and permeability, although the permeability was somewhat more strongly affected
      by water content than by proteoglycan content. Correlation coefficients r<or=0.75
      for the multiple regression indicated water and GAG content can moderately
      predict material properties, however other compositional and structural factors
      must be considered.

PMID- 16598655
TI  - Spatial correlation analysis of isotropic microvessels: methodology and
      application to thyroid capillaries.
AB  - The study of relations between structural organization and functions of
      microcirculatory networks is a major aim of modern microangiology. Such a
      structural aspect of microvessels (MVs) as their spatial arrangement has
      substantial influence on their transport and other functional properties. This
      paper describes a methodology of spatial correlation analysis for isotropic blood
      and lymphatic MVs which is based on a stereological estimator of the pair
      correlation function [g3D(r)] created recently by the authors for systems of
      elongated objects. The following main features of the methodology are presented:
      (i) interpretation of the shape of g3D(r) curves, (ii) their quantitative
      description by numerical parameters, and (iii) limitations of the method arising
      from statistical requirements to MVs under investigation. The methodology is
      considered in the light of multilevel sampling designs, which are typical for
      biomedical morphology. The estimator with its methodological framework is applied
      to perifollicular blood capillaries in the adult rat thyroid. Related methods for
      studying the spatial arrangement of MVs are thoroughly discussed in the paper.

PMID- 16598656
TI  - Models of metabolic utilization predict limiting conditions for sustained power
      from conditioned skeletal muscle.
AB  - Application and development of muscle powered cardiac assist devices is limited
      by the ability to predict the sustainable power output of in situ conditioned
      muscle under the expected loading conditions and geometrical constraints.
      Empirical definition of the sustained power limits and representative models of
      the bounding conditions where continuous power can be obtained are needed for
      device design and optimization. The latissimus dorsi muscles of four goats were
      chronically conditioned for 11 weeks with an implanted myostimulator. The ability
      to sustain power under isotonic conditions was evaluated across a range of
      contraction durations (100-600 ms) and rates (10-120 contractions/min). Muscles
      were characterized both biomechanically and myothermically to develop and
      evaluate three increasingly complex empirically-based models of metabolic
      utilization per contraction based on (1) the duty cycle, (2) a linear function of
      activation time, and (3) a multivariate-derived function of contraction duration,
      muscle load, and shortening distance. A clearly defined boundary for sustainable
      stimulation conditions was observed and was best represented by the linear
      metabolic model. These data provide both an empirical measure of chronically
      sustainable muscle power and predictive metabolic models that may be used to
      optimize the power harnessed for skeletal muscle actuated devices.

PMID- 16598657
TI  - Influence of pertussis toxin on CD1a isoform expression in human dendritic cells.
AB  - Pertussis toxin (PTX) is an exotoxin produced by Bordetella pertussis. It is
      known to exert adjuvant activities inducing Th1-launched immune responses. In
      this study, we show that PTX can selectively block the expression of CD1a isoform
      during the differentiation of human monocytes into dendritic cells. In fact,
      dendritic cells differentiated from monocytes in the presence of PTX do not
      express CD1a on their surface, unlike CD1b and CD1c isoforms, which are normally
      regulated. The impaired CD1a expression on cell membrane depends, at least
      partially, on decreased mRNA transcription and does not affect cellular
      capability to respond to other maturation stimuli. Since CD1a(+) dendritic cells
      are involved in the early steps of primary immune response, the interference of
      PTX in the CD1a expression may be relevant for its employment as adjuvant.

PMID- 16598658
TI  - Latino adults' access to mental health care: a review of epidemiological studies.
AB  - Since the early 1980s, epidemiological studies using state-of-the-art
      methodologies have documented the unmet mental health needs of Latinos adults in
      the U.S. and Puerto Rico. This paper reviews 16 articles based on seven
      epidemiological studies, examines studies methodologies, and summarizes findings
      about how Latino adults access mental health services. Studies consistently
      report that, compared to non-Latino Whites, Latinos underutilize mental health
      services, are less likely to receive guideline congruent care, and rely more
      often on primary care for services. Structural, economic, psychiatric, and
      cultural factors influence Latinos' service access. In spite of the valuable
      information these studies provide, methodological limitations (e.g., reliance on
      cross-sectional designs, scarcity of mixed Latino group samples) constrict
      knowledge about Latinos access to mental health services. Areas for future
      research and development needed to improve Latinos' access and quality of mental
      health care are discussed.

PMID- 16598659
TI  - Beliefs and practices of the parents of violent and oppositional adolescents: an
      ecological perspective.
AB  - Parenting is a transactional process, influenced by the child's behavior and the
      environmental context. The present study explores the beliefs and practices of
      parents of aggressive and oppositional adolescents to understand better the
      relation among parenting practices, context, and youth violence. Parents of
      juvenile offenders (N=203) completed assessments of youths' violent and
      oppositional behaviors, community violence exposure, and their own beliefs and
      parenting behaviors and perceptions of the juvenile justice system. Parents of
      youth with the highest levels of violent and oppositional behavior problems
      reported elevated feelings of hopelessness regarding the child's future,
      inadequacy as a parent, fear of physical harm by the child, anger toward the
      child, as well as difficulty monitoring the child. All parents reported
      relatively high levels of perceived support by the justice system. Parental
      stress was also examined as a possible influence on the parents' beliefs and
      behaviors regarding the child. Results suggest that parents' emotional and
      behavioral responses should be addressed when intervening with juvenile
      offenders. Editors' Strategic Implications: The authors present evidence to
      suggest that parents' perceptions of hopelessness/inadequacy and their fear for
      their child's safety are both by-products of life with an aggressive child as
      well as contributing factors to that aggressive behavior. Thus, successful
      interventions must both target the parents as change agents in the youth's life
      but also include a strong parental support component, so that parents will have
      an opportunity to orchestrate positive impacts in high-risk environments.

PMID- 16598660
TI  - Comparison of two risk assessment instruments for sexual offenders.
AB  - The current research examines the predictive validity of the Static-99 and the
      SORAG in predicting sexual and violent recidivism among a sample of 258 treated
      high-risk sexual offenders. While the SORAG was found to have moderate predictive
      accuracy for both sexual and violent recidivism over a 5-year follow-up period,
      the Static-99 was found to only predict sexual recidivism. As well, the actual
      recidivism rates in the current sample were compared to the published risk
      percentages for each of the instruments. For both the Static-99 and the SORAG the
      current sample re-offended at a lower rate than expected. Possible explanations
      for this finding are discussed.

PMID- 16598662
TI  - Evaluation of the SORAG and the Static-99 on Belgian sex offenders committed to a
      forensic facility.
AB  - This study evaluated the convergent and predictive validity of the Sex Offender
      Risk Appraisal Guide (SORAG; V. L. Quinsey, G. T. Harris, M. E. Rice, & C. A.
      Cormier, 1998) and the Static-99 (R. K. Hanson & D. Thornton, 1999, 2000) among
      147 male sex offenders committed to a high-security hospital in Belgium (Centre
      de Defense Sociale "Les Marronniers"). Of the sample, 63.8% were child abusers
      (victims under 14 years of age), 24.6% were rapists (victims aged 14 years or
      more), and 11.5% were mixed-victim offenders (victims less than 14 years of age
      and victims aged 14 years or more). After an average follow-up period of 4.2
      years (SD = 3.4 years), the sexual recidivism rate was 25.2%, the violent
      recidivism rate was 17.1%, and the general (any) recidivism rate was 33.1%. The
      SORAG and the Static-99 were moderately correlated with each other (r = .55), and
      both showed strong predictive validity for general and violent recidivism (ROC
      AUC's ranging from .68 to .72 for the total sample). Both instruments showed
      moderate predictive validity for sexual recidivism (AUC of .64 for SORAG and .66
      for Static-99).

PMID- 16598661
TI  - Sex offenders' response to treatment and its association with recidivism as a
      function of psychopathy.
AB  - This study examined the relationship between recidivism and ratings of response
      to specialized cognitive behavioral treatment conducted in a prison setting among
      418 sex offenders released to the community for an average follow-up period of
      over 5 years. As well as testing for a main effect for treatment ratings, the
      potential role of psychopathy assessed using the Psychopathy Checklist--Revised
      (PCL-R) as a moderator of response to treatment was investigated. Ratings of
      response to treatment failed to predict either serious (violent including sexual)
      or sexual recidivism. For the more inclusive outcome of serious recidivism, there
      was no significant interaction between psychopathy and treatment ratings;
      however, the ubiquitous effect of psychopathy on recidivism was found to be
      significant. For sexual recidivism, psychopathy was not significant as a main
      effect, but a significant interaction between psychopathy and treatment ratings
      was found. Among sex offenders with PCL-R scores of 25 or higher, those with
      ratings reflecting a more negative response to treatment recidivated sexually at
      a faster rate than others. This interaction effect was not significant when
      treatment noncompleters were removed from the data set. The results were
      discussed in terms of the methodology involved in the assessment of response to
      treatment among sex offenders.

PMID- 16598663
TI  - Phallometric comparison of pedophilic interest in nonadmitting sexual offenders
      against stepdaughters, biological daughters, other biologically related girls,
      and unrelated girls.
AB  - This study compared the mean levels of sexual response to children produced by
      four groups of men with sexual offences against prepubescent girls and two
      comparison groups with other offences or no offences. All groups (N = 291)
      consisted of patients referred for clinical assessment of their sexual behavior
      or interests. Group assignment was determined by the victim's age and her
      relation to the patient: biological daughter; stepdaughter; other biologically
      related girl (e.g., sister, niece, granddaughter); unrelated girl; adult woman;
      and no known victim. The men with sexual offences had precisely one known victim
      each. The patients with offences may or may not have denied the act of which they
      were accused, but all patients denied an erotic preference for children. Sexual
      response to children was assessed by means of phallometric testing, a
      psychophysiological technique in which the individual's penile blood volume is
      monitored while he is presented with a standardized set of laboratory stimuli
      depicting male and female children and adults. The results indicated that the
      mean level of pedophilic response in men with offences against daughters or
      stepdaughters is intermediate between that in men with offences against otherwise
      related or unrelated girls and that in men with no offences against girls at all.

PMID- 16598664
TI  - The environment and staff of residential facilities: findings from the Italian
      'progres' national survey.
AB  - We administered structured interviews to managers and staff of a random sample of
      265 Italian psychiatric Residential Facilities (RFs). Most are independent
      buildings, located in urban and suburban areas. The median number of residents is
      10. The few RFs (5.7%) with more than 20 beds have a higher rate of drop-outs and
      escapes. The average indoor space per resident is 36 square meters, there is
      often a garden, and residents generally live in two-bed rooms. Most facilities
      are located within walking distance of shopping centers or recreational
      facilities. Three-quarters have 24-hour staff coverage. On average, each facility
      has about 10 full-time equivalent workers, with a staff:resident ratio of 0.92.
      Most of the professional input is provided by nurses and auxiliary staff.
      Critical issues to be considered in planning facilities include the physical
      environment, the size, and the staffing patterns.

PMID- 16598666
TI  - Percutaneous minimally invasive therapies in the treatment of bone tumors:
      thermal ablation.
AB  - Many percutaneous image-guided ablative techniques have been utilized in the
      treatment of bone cancers. These techniques are fast becoming a focus in the
      treatment of patients with both benign and malignant forms of bone cancer. This
      article will review the principles of radiofrequency ablation including its use
      in combination with other therapies, cryoablation, and microwave ablation in the
      treatment of osteoid osteomas and bone metastases.

PMID- 16598667
TI  - Toll like receptor-4 expression in lipopolysaccharide induced lung inflammation.
AB  - Bacterial lipopolysaccharides (LPS) initiate immune response through Toll-like
      receptor 4 (TLR4). Because many a times host is confronted with secondary
      bacterial challenges, it is critical to understand TLR4 expression following
      initial provocation. We studied TLR4 expression in rats at various times after
      intra-tracheal instillation of LPS. Although TLR4 mRNA was undetectable in normal
      lungs, it increased at 6h and 12h and declined at 36h post-LPS treatment. Western
      blots showed TLR4 protein at all time points. Immunohistochemistry localized TLR4
      in alveolar septal cells, bronchial epithelium, macrophages and endothelium of
      large and peribronchial blood vessels. Dual label immunoelectron microscopy
      showed co-localization of TLR4 and LPS in the cytoplasm and nucleus of various
      lung and inflammatory cells. Nuclear localization of TLR4 was confirmed with
      Western blots on lung nuclear extracts. We conclude that TLR4 expression in lung
      is sustained up to 36 hours and that TLR4 and LPS are localized in the cytoplasm
      and nuclei of lung cells.

PMID- 16598668
TI  - Cytokeratin-positive subserosal myofibroblasts in gastroduodenal ulcer; another
      type of myofibroblasts.
AB  - To investigate the distribution and origin of alpha-smooth muscle actin (ASMA)
      positive stromal cells in the perforation of human gastroduodenal ulcers.
      Perforative lesions of 24 surgically resected gastroduodenal ulcers were examined
      immunohistochemically for ASMA, HCD, CD34, CD31, CAM5.2 and HMW-CK, and double
      staining of ASMA and CAM5.2 was also performed. In addition, to determine the
      cell source of collagen, in situ hybridization of collagen I mRNA was performed.
      In the normal gastroduodenal wall, the reticular network of CD34-positive stromal
      cells was identified in the muscularis mucosa, submucosa, muscular propria, and
      subserosa. In the subepithelial area, many myofibroblasts were observed, whereas
      no CD34-positive stromal cells were seen. In areas neighboring ulcerative
      lesions, no CD34-positive stromal cells were observed, but a significant number
      of myofibroblasts were present there. In the deep layer of ulceration, numerous
      fusiform or stellate stromal cells strongly positive for ASMA and CAM5.2 were
      observed in the subserosal area around the perforation. In the same site, many
      cells co-expressing ASMA and CAM5.2 were identified by double staining. In
      contrast, in the surface layer of ulceration, stromal cells expressing only ASMA
      were observed. The cytokeratin-positive subserosal myofibroblastic cell in human
      gastroduodenal ulcer is a novel type of myofibroblast.

PMID- 16598670
TI  - Topoisomerase 1A, HER/2neu and Ki67 expression in paired primary and relapse
      ovarian cancer tissue samples.
AB  - In the present study we examined prognostic value of immunohistochemical
      estimation of topoisomerase 1A (TOP 1A) and HER-2/neu expression in ovarian
      cancers treated with platinum-based drugs but not with topotecan and the relation
      between expression of these proteins on the one hand and intensity of
      proliferation (Ki67) on the other. The analyses were performed on 73 samples of
      ovarian carcinoma originating from 43 first-look laparotomies (FLL) and, in 30
      cases, from secondary cytoreductions (SCR)(after chemotherapy) from the same
      patients. In paraffin sections immunohistochemical reactions were performed using
      antibodies directed to HER-2/neu, TOP 1A and Ki67. Kaplan-Meier's analysis
      disclosed a shorter overall survival time in cases with augmented expression of
      TOP 1A at FLL and with higher expression of Ki67 at SCR. A shorter progression
      free time was detected in cases with higher proportion of Ki67 positive cells at
      FLL. No relationship could be disclosed between HER-2/neu expression and the
      studied clinicopathological parameters. The studies confirmed high value of Ki67
      estimation. The augmented expression of TOP 1A was demonstrated to represent an
      unfavourable prognostic factor. Thus, in cases with elevated expression of TOP 1A
      application of topotecan-based therapeutic schemes should be considered.

PMID- 16598669
TI  - Comparison of MR images and histochemical localization of intra-arterially
      administered microglia surrounding beta-amyloid deposits in the rat brain.
AB  - The therapeutic use of microglial cells has recently received some attention for
      the treatment of Alzheimer disease (AD), but few non-invasive techniques exist
      for monitoring the cells after administration. Here we present a magnetic
      resonance imaging (MRI) technique for tracking microglia injected intra
      arterially in vivo. We micro-injected Abeta42 into the left hippocampus and
      saline into the right hippocampus of rats. We then administered microglia, which
      were labeled with enhanced green fluorescent protein (EGFP) gene and Resovist,
      into the carotid artery. After monitoring exogenously administered microglia
      using MRI, we compared the MR images and the histochemical localization of
      administered microglia. MRI revealed clear signal changes attributable to
      Resovist-containing microglia in Abeta-injected areas. Histochemistry
      demonstrated that EGFP-positive microglia accumulated around Abeta deposits and
      internalized the peptide. This study demonstrates the usefulness of MRI for non
      invasive monitoring of exogenous microglia, and suggests a promising future for
      microglia/macrophages as therapeutic tools for AD.

PMID- 16598671
TI  - Quantitative cell-cycle protein expression in oral cancer assessed by computer
      assisted system.
AB  - The knowledge of cell-cycle control has shown that the capacity of malignant
      growth is acquired by the stepwise accumulation of defects in specific genes
      regulating cell growth. Histologic diagnosis might be improved by a quantitative
      evaluation of more specific diagnosis biomarkers, which could help to precisely
      identify pre-malignant and malignant oral lesions. The aim of the present study
      is to evaluate whether computer-based quantitative assessment of p53, PCNA and Ki
      67 immunohistochemical expression, could be used clinically to foresee the risk
      of oral malignant transformation. This retrospective study was carried out in
      ninety-five oral biopsies, 27 were classified as fibrous inflammatory
      hyperplasia, 40 as leukoplakia and 28 as oral squamous cell carcinoma. Sixteen
      out of the 40 leukoplakia were diagnosed as non-dysplastic leukoplakia, the other
      24 being dysplastic leukoplakia, of which 50.0% were classified as moderate to
      severe dysplasia. Comparison of the four groups of oral tissues showed
      significant rises in p53 and Ki-67 positivity index, which increased steadily in
      the order benign, pre-malignant, and malignant. In contrast, it was not possible
      to relate higher PCNA levels with pre-malignant and malignant oral lesions. We
      therefore conclude that PCNA immunohistochemistry expression is probably an
      inappropriate marker to identify oral carcinogenesis, whereas joint quantitative
      evaluation of p53 and Ki-67, appears to be useful as a tumor marker, providing a
      pre-diagnostic estimate of the potential for cell-cycle deregulation of the oral
      proliferate status.

PMID- 16598672
TI  - Histological recovery of the hepatocytes is based on the redox system
      upregulation in the animal models of mutant superoxide dismutase (SOD)1-linked
      amyotrophic lateral sclerosis.
AB  - Histological rescue of superoxide dismutase1 (SOD1)-mutated hepatocytes from
      mutant SOD1 stress is investigated from the viewpoint of upregulation of the
      redox system [peroxiredoxin (Prx) and glutathione peroxidase (GPx)].
      Histopathological and immunohistochemical studies using antibodies against
      PrxI/PrxII/GPxI were carried out on specimens from four different strains of
      animal models of mutant SOD1-linked familial amyotrophic lateral sclerosis (ALS).
      In the livers of the ALS animal models in the presymptomatic stage without motor
      neuron loss, both swollen and eosinophilic hepatocytes with vacuolation pathology
      were observed. After developing motor deficits, this swelling and vacuolation
      ceased to be apparent. In the terminal stage when severe motor neuron loss was
      observed, these hepatocytes recovered and appeared normal. In redox system
      related immunohistochemical preparations, almost all of the normal hepatocytes
      expressed the redox system-related enzymes PrxI/PrxII/GPxI. In the presymptomatic
      stage, some hepatocytes did not express redox system-related enzymes. After
      clinical onset, over 75% of hepatocytes showed overexpression of PrxI/PrxII/GPxI,
      i. e., upregulation of the redox system. At the end stage, near normal
      PrxI/PrxII/GPxI expression was observed again in the hepatocytes. Redox system
      upregulation in SOD1-mutated hepatocytes rescues hepatocytes from the mutant SOD1
      stress that leads to motor neuron death.

PMID- 16598673
TI  - Altered patterns of RB expression define groups of soft tissue sarcoma patients
      with distinct biological and clinical behavior.
AB  - BACKGROUND: Function of the retinoblastoma tumor suppressor protein (pRB) may be
      compromised at a genetic level by gene loss or mutation or at a post
      translational level by hyperphosphorylation. In this study, we examined adult
      soft tissue sarcomas (ASTS) to determine if alterations of pRB were associated
      with distinct patterns of pRB expression and clinical outcome. DESIGN: We
      investigated 86 ASTS patients using monoclonal antibodies that distinguish
      between hyperphosphorylated and underphosphorylated pRB products. We also used
      microsatellite analysis to investigate the genetic status of the RB locus. We
      correlated pRB alterations with proliferative activity, and with
      clinicopathological outcomes. RESULTS: Altered patterns of pRB expression are
      common in ASTS occurring in 84% of cases, and it is significantly associated with
      proliferative activity (p<0.001). Patients whose tumors either lack expression of
      pRB, or express hyperphosphorylated forms of pRB, have poor survivals compared to
      patients whose tumors exhibit a normal, underphosphorylated pattern of pRB
      expression (p=0.03). In addition, 63% of cases lacking expression of pRB showed
      loss-of-heterozygosity at the locus. CONCLUSIONS: Inactivation of pRB is common
      in adult STS, which may be due to either gene loss or post-translational
      modification, namely hyper-phosphorylation. Both mechanisms are associated with
      tumor cell proliferation and poor survival.

PMID- 16598674
TI  - Perioperative IFN-alpha to avoid surgically induced immune suppression in
      colorectal cancer patients.
AB  - Surgical treatment of colorectal cancer is associated with postoperative
      immunosuppression, which might facilitate dissemination of tumor cells and
      outgrowth of minimal residual disease/(micro) metastases. Minimal residual
      disease has been shown to be of prognostic relevance in colorectal cancer.
      Therefore, stimulation of (anti-tumor) immune responses may be beneficial in the
      prevention of metastases formation. Important anti-tumor effector cells, which
      serve this function, are natural killer (NK) cells, CD8+ lymphocytes (CTL),
      dendritic cells (DC) and macrophages. In this review the immunomodulating
      properties of IFN-alpha are discussed, with a particular focus on perioperative
      stimulation of immune function in cancer patients. IFN-alpha is known to enhance
      innate immune functions such as stimulation of NK cells, transition from innate
      to adaptive responses (activation of DC) and regulating of CD8+ CTL activity and
      memory. Moreover, it exerts direct antitumor effects by regulating apoptosis and
      cell cycle. In several clinical trials, perioperative administration of IFN-alpha
      has indeed been shown to improve T cell responsiveness, prevent impairment of NK
      cell cytotoxicity and increase expression of activation markers on NK, T and NKT
      cells. In a clinical pilot study we showed in colorectal cancer patients that
      received perioperative IFN-alpha enhanced activation markers on T cells and NK
      cells, combined with better-preserved T cell function as indicated by
      phytohemaggluttinin skin tests. In the liver of these patients significantly more
      CD8+ T cells were found. In conclusion, IFN-alpha provides an effective adjuvant
      in several forms of cancer and improves several postoperative immune functions in
      perioperative administration. However, larger clinical trials are necessary to
      investigate effects on disease-free and overall survival.

PMID- 16598675
TI  - Role of WNT signaling in normal and malignant hematopoiesis.
AB  - The WNT pathway is a powerful signaling pathway that plays a crucial role in cell
      fate determination, survival, proliferation and movement in variety of tissues.
      Abnormalities in the WNT signaling pathway have been implicated in a number of
      diseases, most notably cancer. Recent exciting evidence suggests that WNT
      signaling also plays an important role in hematopoietic stem cell self-renewal
      and progenitor development. In this review we discuss current state of knowledge
      on WNT signaling in hematopoiesis and extend our focus on aberrant WNT signaling
      in hematological malignancies.

PMID- 16598676
TI  - Cardiac natriuretic peptides: hormones with anticancer effects that localize to
      nucleus, cytoplasm, endothelium, and fibroblasts of human cancers.
AB  - Four cardiac peptide hormones, i.e., vessel dilator, long acting natriuretic
      peptide (LANP), kaliuretic peptide, and atrial natriuretic peptide (ANP)
      synthesized by the same gene decrease within 24 hours up to 97% the number of
      human breast, colon, pancreatic, and prostate adenocarcinoma cells as well as
      human small-cell and squamous carcinomas of the lung cells. These peptide
      hormones completely inhibit the growth of human pancreatic adenocarcinomas
      growing in athymic mice. Immunocytochemical investigations have revealed that
      LANP, vessel dilator, kaliuretic peptide and ANP localize to the nucleus and
      cytoplasm of human pancreatic adenocarcinomas, which is consistent with their
      ability to decrease DNA synthesis in the nucleus of this cancer mediated by the
      intracellular messenger cyclic GMP. These peptide hormones also localize to the
      endothelium of capillaries and fibroblasts within these cancers. These are the
      first growth-inhibiting peptide hormones ever demonstrated to localize to the
      nucleus. Their ability to decrease the activation of growth promoting substances
      such as Extracellular Receptor Kinase (ERK)-1/2 and Nuclear Factor Kappa Beta
      (NFkappaB) suggests that in addition to inhibiting DNA synthesis their ability to
      decrease the activation of growth promoting substances helps to mediate their
      ability to inhibit the growth of human cancers.

PMID- 16598677
TI  - Histone modifications in status epilepticus induced by kainate.
AB  - Animal models of epilepsy have allowed the determination of the basic molecular
      and cellular mechanisms of epileptogenesis. Generalized limbic seizures and
      subsequent status epilepticus can be induced by either pilocarpine, the
      muscarinic acetylcholine receptor agonist or kainate, the glutamate receptor
      agonist. There has been increasing interest that chromatin remodeling might play
      a critical role in gene regulation even in non-dividing cells such as neurons.
      One form of chromatin remodeling is histone amino-terminal modification that can
      generate synergistic or antagonistic affinities for the interactions of
      transcriptional factors, in turn causing changes in gene activity. Two widely
      studied histone modification processes are histone acetylation and
      phosphorylation. While histone hyperacetylation indicates an increase in gene
      activity, its hypoacetylation marks gene repression. Both states are controlled
      by a dynamic interplay of histone acetyltransferase (HAT) and histone deacetylase
      (HDAC). We have found the upregulation of acetylation and phosphorylation of
      histones, coupled with status epilepticus after kainate administration. c-fos and
      c-jun mRNA have been sequentially induced in response to kainate, in different
      hippocampal subpopulations starting from the dentate gyrus and spreading to the
      cornus ammonis regions well correlated with the spatio-temporal distribution of
      histone H4 hyperacetylation. Both histone modifications are associated with the c
      fos gene promoter after kainate stimulation, while only histone acetylation with
      the c-jun gene. Pretreatment with curcumin, which has a HAT inhibitory activity
      specific for CBP/p300, attenuates histone modifications, IEGs expression and also
      the severity of status epilepticus after kainate treatment. Histone modifications
      may have a crucial role in the development of epilepsy induced by kainate.

PMID- 16598678
TI  - Do chondrocytes undergo "activation" and "transdifferentiation" during the
      pathogenesis of osteoarthritis? A review of the ultrastructural and
      immunohistochemical evidence.
AB  - Chondrocytes, which are the only cell type in the articular cartilage, show
      substantial morphological and functional differences, depending on their location
      within the tissue. In OA cartilage, outstanding modifications have been reported
      concerning their structure and functions. Based on the principle that both
      structure and function run in a parallel manner, new concepts are arising related
      to morphological observations. Observations on OA chondrocytes, such as
      cytoskeleton disruption, development of the secretory machinery (rough
      endoplasmic reticulum and Golgi complex), and cell death by apoptosis, among
      others, certainly must be related to the role of chondrocytes in OA pathogenesis.
      In this degradative process, it has been acknowledged that cell death, matrix
      degradation and subchondral bone remodelling are the main causes of cartilage
      breakdown in osteoarthritis. The aim of this review was to correlate and
      integrate in a logical manner the modifications of chondrocytes with cartilage
      breakdown during osteoarthritis pathogenesis. Furthermore, we intend to open a
      debate on cell cycle and mitosis, as well as on signalling molecules that might
      be involved in the morphofunctional changes in OA chondrocytes, which we propose
      to name "activation" and "transdifferentiation" of chondrocytes. We expect this
      analysis to be useful for studying OA pathogenesis in depth, with the aim of
      finding new strategies for the early diagnosis and therapeutic procedures for
      this invalidating disease, which is already an important public health problem.

PMID- 16598679
TI  - Accurate diagnosis of Giardia spp and proper fecal examination procedures.
AB  - A series of investigations evaluated the ability of different testing methods - a
      swing-head centrifugation technique using two flotation solutions (1.18-specific
      gravity zinc sulfate and 1.27-specific gravity Sheather's sugar solution), a
      passive commercial flotation technique, and the SNAP Giardia Test Kit from IDEXX
      Laboratories - to identify Giardia-positive dogs and recover the eggs of other
      intestinal parasites. It was determined that the SNAP Giardia test can improve a
      practice's ability to identify Giardia-infected dogs. Because of its higher
      specific gravity, the sugar solution was better for recovering heavy parasite
      eggs, such as Taenia spp, and thus is the flotation solution of choice when
      conducting routine centrifugation fecal examinations.

PMID- 16598680
TI  - The efficacy of an antiseptic and microbial anti-adhesive ear cleanser in dogs
      with otitis externa.
AB  - A new antimicrobial ear cleanser was evaluated for the treatment of bacterial and
      yeast ear infection in dogs. Forty-five dogs with erythemato-ceruminous or
      purulent otitis externa were randomly allocated to two treatment groups:
      reference ear cleanser (Epiotic, Virbac) or test ear cleanser (Epiotic Advanced,
      Virbac). Ear cleansing was performed twice daily for 2 weeks, and no other
      treatment was allowed. By week 2, clinical (exudate quantity, erythema, stenosis,
      excoriation, and odor) and discomfort (pain, ear scratching, and head shaking)
      scores were significantly decreased (P < .0001 for all) and no microbial
      overgrowth could be detected in 25 (64.1%) and 32 (68.1%) ears treated with
      Epiotic and Epiotic Advanced, respectively. The new pH-balanced, propylene glycol
      free test ear cleanser, which incorporates microbial adhesin-blocking
      carbohydrates, proved as effective as the reference acidic formula.

PMID- 16598681
TI  - Protection against fetal infection with either bovine viral diarrhea virus type 1
      or type 2 using a noncytopathic type 1 modified-live virus vaccine.
AB  - Two bovine viral diarrhea virus (BVDV) fetal protection studies were done using a
      monovalent noncytopathic (NCP) BVDV vaccine containing type 1 BVDV. In study 1,
      thirty-two fetuses (23 vaccinates and nine controls) were recovered following
      fetal challenge with the type 1a BJ strain. Twenty of twenty-three fetuses from
      the vaccinates were negative for BVDV type 1 while all of the controls (nine of
      nine) were infected. In study 2, twenty-two animals (14 vaccinates and eight
      controls) were challenged with the type 2 PA131 strain. Thirteen of the fourteen
      fetuses from the vaccinates were negative for BVDV type 2 while all of the
      nonvaccinated controls (eight of eight) were infected. These results indicate the
      efficacy of a monovalent NCP BVDV vaccine in providing excellent protection
      against either BVDV type 1 or 2 fetal infection.

PMID- 16598682
TI  - Efficacy of intramammary infusion of ceftiofur hydrochloride at drying off for
      treatment and prevention of bovine mastitis during the nonlactating period.
AB  - This study evaluated the efficacy of intramammary infusion of ceftiofur
      hydrochloride for the treatment of intramammary infections present at the last
      milking of lactation and for prevention of new intramammary infections during the
      nonlactating period. Cows were randomly assigned to five treatments (untreated
      negative control, 125, 250, and 500 mg of ceftiofur, and a positive control group
      receiving 300 mg cephapirin benzathine). A dose of 125 mg of ceftiofur per
      mammary quarter was effective for treatment of existing infections present at the
      time of milk cessation, but only the 500-mg dose of ceftiofur per mammary quarter
      was effective for both treatment of existing intramammary infections at the time
      of milk cessation and for prevention of new intramammary infections during the
      nonlactating period.

PMID- 16598683
TI  - A field trial evaluation of the effectiveness and benefit of cydectin long-acting
      injectable and ivomec injectable as used one time in grazing stocker cattle.
AB  - Use of moxidectin long-acting injectable and ivermectin injectable in female Bos
      taurus beef-type calves was evaluated in terms of efficacy (fecal egg counts) and
      performance parameters (weight gain). In this 150-day study, moxidectin-treated
      calves gained 20% more weight than did ivermectin-treated and control calves.
      Mean fecal egg count reductions ranged from 76.7 to 99.0 for moxidectin and -0.8
      to 83.4 for ivermectin. Moxidectin long-acting injection provided efficacious
      (immediate as well as long-term) egg count suppressions as well as enhanced
      animal productivity (weight gains). The study also showed that Cooperia spp
      appear poised to present the most immediate challenges once long-acting
      macrocyclic lactone treatments become available.

PMID- 16598684
TI  - New therapeutic approaches for equine protozoal myeloencephalitis:
      pharmacokinetics of diclazuril sodium salts in horses.
AB  - Diclazuril is a triazine-based antiprotozoal agent which may have clinical
      application in the treatment of equine protozoal myeloencephalomyelitis (EPM). In
      this study, the use of the sodium salt diclazuril to increase the apparent
      bioavailability of diclazuril for the treatment and prophylaxis of EPM and
      various other Apicomplexan mediated diseases is described. In this study,
      diclazuril sodium salt was synthesized and administered to horses as diclazuril
      sodium salt formulations. The absorption, distribution, and clearance of
      diclazuril sodium salt in the horse are described. Diclazuril was rapidly
      absorbed, with peak plasma concentrations occurring at 8-24 hours following an
      oral mucosal administration of diclazuril sodium salt. The mean oral
      bioavailability of diclazuril as Clinacox was 9.5% relative to oral mucosal
      administration of diclazuril sodium salt. Additionally, diclazuril in DMSO
      administered orally was 50% less bioavailable than diclazuril sodium salt
      following an oral mucosal administration. It was also shown that diclazuril
      sodium salt has the potential to be used as a feed additive for the treatment and
      prophylaxis of EPM and various other Apicomplexan mediated diseases.

PMID- 16598685
TI  - Modulation of leptin, insulin, and growth hormone in obese pony mares under
      chronic nutritional restriction and supplementation with ractopamine
      hydrochloride.
AB  - Horses fed beyond their nutritional requirement and that are physically inactive
      will develop obesity, which is often accompanied by insulin resistance and
      heightened risk of laminitis. The use of pharmacologic agents in combination with
      nutritional restriction may promote weight loss in obese horses unable to
      exercise because of laminitic pain. This study shows that reducing feed intake of
      brome grass hay to 75% of ad libitum intake in obese pony mares reduces body
      weight without induced exercise. Additional supplementation of ractopamine
      hydrochloride for 6 weeks resulted in a tendency for increased weight loss.
      Subsequent modulation of obesity-associated hormones, leptin and insulin, as a
      result of caloric restriction was observed.

PMID- 16598687
TI  - Genome-wide identification of genes required for growth of Saccharomyces
      cerevisiae under ethanol stress.
AB  - The Saccharomyces cerevisiae deletion collection was screened for impaired growth
      on glucose-based complex medium containing 6% ethanol. Forty-six mutants were
      found. Genes encoding proteins involved in vacuolar function, the cell integrity
      pathway, mitochondrial function, subunits of the co-chaperone complex GimC and
      components of the SAGA transcription factor complex were in this way found to be
      important for the growth of wild-type Saccharomyces yeast in the presence of
      ethanol. Several mutants were also sensitive to Calcofluor white (14 mutants),
      sorbic acid (9), increased temperature (5) and NaCl (3). The transcription
      factors Msn2p and Ars1p, tagged with green fluorescent protein, were translocated
      to the nucleus upon ethanol stress. Only one of the genes that contain STRE
      elements in the promoter was important under ethanol stress; this was TPS1,
      encoding trehalose 6-phosphate synthase. The map kinase of the cell integrity
      pathway, Slt2p, was phosphorylated when cells were treated with 6% ethanol. Two
      out of three mutants tested fermented 20% glucose more slowly than the wild-type.

PMID- 16598688
TI  - Glycolytic sequence and respiration of Debaryomyces hansenii as compared to
      Saccharomyces cerevisiae.
AB  - The fermentation and respiration activities of Debaryomyces hansenii were
      compared with those of Saccharomyces cerevisiae grown to stationary phase with
      high respiratory activity. It was found that: (a) glucose consumption,
      fermentation and respiration were lower than for S. cerevisiae; (b) fasting
      produced a much smaller decrease of respiration; (c) glucose consumed and not
      transformed to ethanol was higher; (d) in S. cerevisiae, full oxygenation
      prevented ethanol production but this effect was reversed by CCCP, whereas D.
      hansenii still showed some ethanol production under aerobiosis, which was
      moderately increased by CCCP. ATP levels were similar in the two yeasts. Levels
      of glycolytic intermediaries after glucose addition, and enzyme activities,
      indicated that the main difference and limiting step to explain the lower
      fermentation of D. hansenii is phosphofructokinase activity. Respiration and
      fermentation, which are lower in D. hansenii, compete for the re-oxidation of
      reduced nicotinamide adenine nucleotides; this competition, in turn, seems to
      play a role in defining the fermentation rates of the two yeasts. The effect of
      CCCP on glucose consumption and ethanol production also indicates a role of ADP
      in both the Pasteur and Crabtree effects in S. cerevisiae but not in D. hansenii.
      D. hansenii shows an alternative oxidase, which in our experiments did not appear
      to be coupled to the production of ATP.

PMID- 16598689
TI  - The Schizosaccharomyces pombe cfr1+ gene participates in mating through a new
      pathway that is independent of fus1+.
AB  - Conjugation is a complex event directed to ensure the transfer of genetic
      material, which is achieved by the union of two cells. In fungi, success of this
      relevant process requires digestion of the cell wall at the point where both
      cells have agglutinated and, later, the union of the plasma membranes and nuclei
      from the mating partners. In order to gain information about cell fusion, we have
      cloned and disrupted the cfr1+ gene from the fission yeast Schizosaccharomyces
      pombe. cfr1+ gene is slightly induced at the beginning of mating but Cfr1p
      protein is degraded soon after the cells are transferred to nitrogen-lacking
      medium. cfr1Delta mutants present a defect in cell fusion owing to a failure in
      the digestion of the cell walls between the two parental cells. Finally,
      cytological and genetic analyses show that cfr1+ acts in a new pathway involved
      in conjugation that is independent of fus1+, the only gene that has been found to
      be specifically required for cell fusion during mating in the fission yeast.

PMID- 16598690
TI  - Involvement of yeast YOL151W/GRE2 in ergosterol metabolism.
AB  - The Saccharomyces cerevisiae gene YOL151W/GRE2 is widely used as a model gene in
      studies on yeast regulatory responses to osmotic and oxidative stress.
      Nevertheless, information concerning the physiological role of this enzyme, a
      distant homologue of mammalian 3-beta-hydroxysteroid dehydrogenases, is scarce.
      Combining quantitative phenotypic profiling and protein expression analysis
      studies, we here report the involvement of yeast Gre2p in ergosterol metabolism.
      Growth was significantly and exclusively reduced in gre2Delta strains subjected
      to environmental stress straining the cell membrane. Furthermore, whereas no
      compensatory mechanisms were activated due to loss of Gre2p during growth in
      favourable conditions (synthetic defined media, no stress), a striking and highly
      specific induction of the ergosterol biosynthesis pathway, represented by the
      enzymes Erg10p, Erg19p and Erg6p, was observed in gre2Delta during growth in a
      stress condition in which lack of Gre2p significantly affects growth. Involvement
      of Gre2p in ergosterol metabolism was confirmed by application of an array of
      selective inhibitors of lipid biosynthesis, as gre2Delta displayed vastly
      impaired tolerance exclusively to agents targeting the ergosterol biosynthesis.
      The approach outlined here, combining broad-spectrum phenotypic profiling,
      expression analysis during conditions reducing the growth of the mutant and
      functional confirmation by application of highly selective inhibitors, may prove
      a valuable tool in gene functional analysis.

PMID- 16598691
TI  - PCR-mediated seamless gene deletion and marker recycling in Saccharomyces
      cerevisiae.
AB  - Repeated gene manipulations can be performed in yeast by excision of an
      introduced marker. Cassette modules containing a marker flanked by two direct
      repeat sequences of hisG or loxP have often been used for marker recycling, but
      these leave one copy of the repeats in the chromosome after excision. Genomic
      copies of a repeat can cause increased mistargeting of constructs containing the
      same repeats or unexpected chromosomal rearrangements via intra- or
      interchromosomal recombinations. Here, we describe a novel marker recycling
      procedure that leaves no scar in the genome, which we have designated seamless
      gene deletion. A 40 base sequence derived from an adjacent region to the targeted
      locus was placed in an integrating construct to generate direct repeats after
      integration. Seamless HIS3 deletion was achieved via a PCR fragment that
      consisted of a URA3 marker attached to a 40 base repeat-generating sequence
      flanked by HIS3 targeting sequences at both ends. Transformation of the designed
      construct resulted in his3 disruption and the generation of 40 base direct
      repeats on both sides of URA3 in the targeted locus. The resulting his3::URA3
      disruptants were plated on 5-fluoroorotic acid medium to select for URA3 loss.
      All the selected colonies had lost URA3 precisely by recombination between the
      repeats, resulting in his3 deletion without any extraneous sequences left behind
      in the chromosome.

PMID- 16598694
TI  - Machine learning approaches for prediction of linear B-cell epitopes on proteins.
AB  - Identification and characterization of antigenic determinants on proteins has
      received considerable attention utilizing both, experimental as well as
      computational methods. For computational routines mostly structural as well as
      physicochemical parameters have been utilized for predicting the antigenic
      propensity of protein sites. However, the performance of computational routines
      has been low when compared to experimental alternatives. Here we describe the
      construction of machine learning based classifiers to enhance the prediction
      quality for identifying linear B-cell epitopes on proteins. Our approach combines
      several parameters previously associated with antigenicity, and includes novel
      parameters based on frequencies of amino acids and amino acid neighborhood
      propensities. We utilized machine learning algorithms for deriving antigenicity
      classification functions assigning antigenic propensities to each amino acid of a
      given protein sequence. We compared the prediction quality of the novel
      classifiers with respect to established routines for epitope scoring, and tested
      prediction accuracy on experimental data available for HIV proteins. The major
      finding is that machine learning classifiers clearly outperform the reference
      classification systems on the HIV epitope validation set.

PMID- 16598696
TI  - Single-scan quantitative T2* methods with susceptibility artifact reduction.
AB  - Two imaging methods, MSSAVE (Multiple echo SubSlice AVEraging imaging), based on
      sub-slice averaging and MGESEPI (Multiple echo Gradient-Echo Slice-Excitation
      Profile Imaging), based on over-sampling in the slice direction, are proposed for
      single-scan quantitative T(2)* evaluation with susceptibility artifact
      compensation. Their potentials in terms of sensitivity, minimum performance time,
      susceptibility artifact reduction and T(2)* quantitation quality, were compared
      with existing single-scan methods such as classical FLASH two- or three
      dimensional or z-shimmed methods both in vitro and in vivo in normal rat brain.
      MGESEPI offered good quality T(2)* maps nearly free of artifacts but required a
      long acquisition time. MSSAVE was faster, but at the expense of reduced artifact
      compensation and the achievable T(2)* quantitation quality.

PMID- 16598695
TI  - Dependence of gradient-echo and spin-echo BOLD fMRI at 4 T on diffusion
      weighting.
AB  - Diffusion weighting and spin-echo (SE) acquisitions can be used to help improve
      the spatial localization of BOLD fMRI at the cost of reduced acquisition rates
      and lower signal-to-noise ratio (SNR). To evaluate these costs, SE and gradient
      echo (GE) data were acquired at 4 T at five diffusion weightings ranging from b =
      0 to 1110 s/mm(2) using a robust visual stimulus. The data showed reduced
      functional contrast when diffusion weighting was applied. As the amount of
      diffusion weighting increased, the functional contrast initially dropped sharply,
      and then remained relatively constant for diffusion weightings above 15 s/mm(2)
      for SE and 30 s/mm(2) for GE data. GE functional BOLD contrast was attenuated to
      94.0 +/- 10.1, 87.6 +/- 12.2, 86.4 +/- 8.8 and 83.3 +/- 20.6% of the non
      diffusion-weighted GE contrast for diffusion weightings of 15, 30, 200 and 1,110
      s/mm(2). The non-diffusion-weighted SE contrast greatly reduced to 19.3 +/- 3.3%
      of the non-diffusion-weighted GE contrast, demonstrating the large activation
      attenuation of a SE acquisition. The SE contrast was further reduced to 10.0 +/-
      3.6, 9.0 +/- 2.5 and 8.6 +/- 2.0% of the non-diffusion-weighted GE contrast for
      the 15, 30 and 200 s/mm(2) diffusion-weighted data. These results suggest that
      only a small amount of diffusion weighting is necessary to suppress the vascular
      contribution and spin-echo imaging should only be used if there is adequate
      statistical power available or accurate localization is critical.

PMID- 16598697
TI  - 1H NMR spectroscopy for the prediction of therapeutic outcome in patients with
      fulminant hepatic failure.
AB  - A high-resolution (1)H NMR study of serum and urine of fulminant hepatic failure
      patients (n = 22) [surviving (n = 12) and non-surviving (n = 10)] is reported.
      Glutamine in serum and urine glutamine:creatinine ratio were higher in non
      surviving patients compared with surviving patients [serum glutamine, 3.08 (1.68
      7.11) vs 0.56 (0.34-0.99) mM, median and range; p = 0.0001 and urine
      glutamine:creatinine ratio, 1.72 (0.24-7.76) vs 0.39 (0.1-0.84), p = 0.1], and
      urine urea:creatinine ratio was higher in surviving patients compared with non
      surviving patients [10.83 (0.2-22.6) vs 2.09 (0.96-4.0), p = 0.002]. On the other
      hand, no significant differences were found in the conventionally employed
      clinical parameters such as serum alanylaminotransferase,
      aspartylaminotransferase and bilirubin except prothrombin time (p = 0.02). The
      difference in serum glutamine and urine urea was significant in the two
      categories of patients and distinctly different values of serum glutamine for
      both the categories of patients correctly predicted the outcome. These results
      promise immense potential for NMR spectroscopy in rapidly deciding on the need
      for advanced therapeutic intervention such as artificial liver support or
      emergency liver transplantation in FHF.

PMID- 16598698
TI  - Hypomagnesemia, oxidative stress, inflammation, and metabolic syndrome.
AB  - BACKGROUND: Although hypomagnesemia, oxidative stress, and inflammation are
      involved in the pathogenesis of cardiovascular diseases, there is not a previous
      description concerning their potential interaction; thus, the aim of this study
      was to examine the relationship between metabolic syndrome (MetS),
      hypomagnesemia, inflammation, and oxidative stress. METHODS: Case-control design
      study. Incident cases of MetS (84 women and 63 men) were compared with healthy
      control subjects (163 women and 131 men) matched by age and gender. MetS was
      diagnosed according to the Adult Treatment Panel III (ATP III) criterion.
      Oxidative stress was defined by serum malondialdehyde concentration (MDA) > or
      =50 mg/dL, low-grade chronic inflammation by C-reactive protein (CRP) serum
      levels > or =3 mg/L, and hypomagnesemia by serum magnesium concentrations < or
      =1.8 mg/dL. RESULTS: Multivariate analysis adjusted by age, sex, body mass index,
      waist-to-hip ratio, and total adiposity showed a strong association between MetS
      and hypomagnesemia (OR 1.9; 95% CI 1.3-7.1), inflammation (OR 1.7; 95% CI 1.4
      8.4), and oxidative stress (OR 1.4; 95% CI 0.9-12.6). Additional adjustment by
      CRP levels showed that MetS remained associated to hypomagnesemia (OR 1.4; 95% CI
      1.1-5.9) but not to oxidative stress (OR 1.1; 95% CI 0.9-5.9), and adjusted by
      MDA levels, MetS remained strongly associated to hypomagnesemia (1.6; CI 95% 1.1
      7.4), but not to inflammation (OR 1.05; 95% CI 0.97-14.2). Adjusted by serum
      magnesium levels, inflammation (OR 1.2; 95% CI 1.1-9.1) and oxidative stress (OR
      1.1; 95% CI 1.1-9.7) were slightly associated to MetS. CONCLUSIONS: The
      interaction of inflammation and oxidative stress is related and increases the
      risk for MetS, whereas serum magnesium levels and MetS are independently
      associated.

PMID- 16598700
TI  - Impact of changes to the American Joint Committee on Cancer T classification on
      outcome prediction in patients with oropharyngeal cancer.
AB  - BACKGROUND: The efficacy of the current 6th edition of the American Joint
      Committee on Cancer (AJCC) tumor staging criteria in improving outcome prediction
      for patients with oropharyngeal cancer was analyzed. METHODS: From the database
      of the Department of Radiation Oncology at the University of Texas M. D. Anderson
      Cancer Center the authors identified 875 patients irradiated at the study
      institution for oropharyngeal cancer between January 1975 and December 1998. The
      tumors were restaged based on the 6th edition of AJCC tumor staging criteria to
      reassess the original outcome predictions, specifically overall survival (OS) and
      local control (LC). RESULTS: Applying the new 6th edition staging system resulted
      in the following T classification distributions: T2, 301 tumors (34%); T3, 248
      tumors (28%); T4a, 224 tumors (26%), and T4b, 102 tumors (12%). The 5-year and 10
      year OS rates based on the new system were: T2, 65% and 45%; T3, 44% and 28%;
      T4a, 30% and 23%; and T4b, 26% and 12%, respectively. The 5-year and 10-year
      actuarial local LC rates based on the new system were: T2, 85% and 83%; T3, 73%
      and 71%; T4a, 61% and 58%; and T4b, 42% and 42%, respectively. Differences in OS
      and LC rates stratified by stage were found to be statistically significant both
      for the overall distribution of survival and pairwise comparisons of the 4 tumor
      stage groups. CONCLUSIONS: The modifications established in the 6th edition of
      the AJCC tumor staging system for oropharyngeal tumors appear to be useful to
      distinguish prognostic groups for both LC and OS based on tumor stage.

PMID- 16598699
TI  - A family of destabilized cyan fluorescent proteins as transcriptional reporters
      in S. cerevisiae.
AB  - The 'programmable' features of the N-end rule degradation pathway and a ubiquitin
      fusion strategy were exploited to create a family of destabilized cyan
      fluorescent proteins (CFP) to be used as transcriptional reporters. The N-degron
      CFP reporters characterized in this report have half-lives of approximately 75,
      50 and 5 min, but further modification of the N-degron signal sequences could
      readily generate additional variants within this range. These destabilized CFP
      reporters have been engineered into convenient plasmid constructs with features
      to enable their expression from upstream activating sequences of choice and to
      facilitate their targeted integration to the URA3-TIM9 intergenic region of
      chromosome V. The advantages and limitations of these reporters as temporal
      indicators of gene expression in living cells are illustrated by their
      application as reporters of galactose- and pheromone-induced transcription. The
      plasmid design we describe and the range of different stabilities that are
      theoretically feasible with this strategy make the N-degron CFP reporters easily
      adapted to a variety of applications.

PMID- 16598701
TI  - Preoperative steroid pulse therapy for invasive thymoma: clinical experience and
      mechanism of action.
AB  - BACKGROUND: Glucocorticoid was used in thymomas. The purpose of the study was to
      evaluate the efficacy of intravenous high-dose glucocorticoid (steroid pulse)
      therapy in patients with previously untreated advanced thymoma. Causes were also
      sought for a possible underlying mechanism of the effect of steroid on thymoma.
      METHODS: Seventeen patients with invasive thymoma who had not received previous
      chemotherapy or radiation therapy were enrolled in the study. All cases were
      treated with 2 courses of glucocorticoid therapy before surgery. Tumor response
      was assessed by computed tomography (CT) scan 1 week after the steroid pulse
      therapy. Lymphocytes associated with thymoma were analyzed for their CD4/CD8
      phenotype and glucocorticoid receptor (GR). TdT-mediated dUTP-biotin nick-end
      labeling (TUNEL) staining was used to analyze the apoptotic lymphocytes and
      epithelial cells. RESULTS: The overall response rate to the steroid pulse therapy
      was 47.1% (8 of 17). The reduction in tumor size was most prominent in type B1
      thymomas; there were significant differences between type AB and type B1 thymomas
      (P = .0234) and type B1 and type B3 thymomas (P = .0068). The reduction in tumor
      size was accompanied with a marked reduction in the CD4+8+ double-positive
      immature thymocytes that expressed higher levels of glucocorticoid receptor.
      Apoptotic changes were observed in both neoplastic epithelial cell and lymphocyte
      components after glucocorticoid therapy. CONCLUSIONS: The efficiency of
      preoperative steroid pulse therapy in type B1 thymoma was most prominent, which
      is probably related to the specific effect on GR-rich CD4+8+ double-positive
      immature lymphocytes, which are abundant in this type of thymoma.

PMID- 16598702
TI  - Age and APOE-epsilon4 genotype influence the effect of physostigmine infusion on
      the in-vivo distribution volume of the muscarinic-2-receptor dependent tracer
      [18F]FP-TZTP.
AB  - The apolipoprotein E-epsilon4 allele (APOE-epsilon4) confers greater
      susceptibility to age-related memory disorders. Abnormalities in the cholinergic
      system are likely contributors to these disorders with both age and APOE-epsilon4
      genotype modifying behavioral and physiological responses to drugs that alter
      cholinergic pathway function. Recently, we reported a greater in vivo
      distribution volume of the F-18 labeled muscarinic-2 (M2) selective agonist, 3-(3
      (3-[18F]Flouropropyl)thio)-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1
      methylpyridine ([18F]FP-TZTP), in aging healthy subjects with an APOE-epsilon4
      allele. To examine the effects of aging and the APOE-epsilon4 allele on the
      response of the muscarinic component of cholinergic pathway to pharmacologic
      augmentation, two [18F]FP-TZTP PET scans were conducted in 19 subjects varying in
      age from 22 to 74 years, the first served as baseline for the second scan that
      was performed while the subjects were either infused with saline (n = 6) or with
      the acetylcholinesterase inhibitor physostigmine (6 with an APOE-epsilon4 allele
      and 7 without an APOE-epsilon4 allele). Using a multiple regression analysis,
      both AGE (beta = 0.621 +/- 0.135, B = 0.353 +/- 0.077, t(10) = 4.61, P < 0.001)
      and APOE-epsilon4 genotype (beta = 0.742, B = 14.8 +/- 2.69, t(10) = 5.51, P <
      0.0003) were found to be significant contributors to subject response to
      physostigmine. The adjusted R2 for the model as a whole was 0.786 (F(2,10) =
      23.00, P < 0.0002) with both increasing age and the presence of the APOE-epsilon4
      allele modifying the response to physostigmine in the direction of larger
      decreases in [18F]FP-TZTP distribution volumes in all brain regions examined. The
      findings, particularly the absence of an interaction between AGE and APOE
      epsilon4 genotype, contribute to the growing body of evidence that suggests that
      the APOE-epsilon4 genotype is likely to contribute to brain structure and
      function prior to aging.

PMID- 16598703
TI  - Subthalamic nucleus lesioning inhibits expression and phosphorylation of c-Jun in
      nigral neurons in the rat's 6-OHDA model of Parkinson's disease.
AB  - Parkinson's Disease (PD) is characterized by a loss of nigral dopamine (DA)
      neurons, followed by a striatal DA deficit. Inhibition of the subthalamic nucleus
      (STN) reverses L-DOPA sensitive motor symptoms and improves efficacy of
      pharmacotherapy in PD-patients. The underlying mechanism of these effects,
      however, remains largely unknown. Previously, we could show in the rat's 6
      hydroxyDA (6-OHDA) model of PD that ablative STN-lesioning exerts functionally
      neuroprotective effects on the DAergic nigrostriatal pathway against 6-OHDA
      toxicity, in terms of elevating the number of tyrosine hydroxylase (TH)
      expressing neurons rather than enhancing the total number of cells surviving 2
      and 6 weeks post lesioning, as assessed via fluorogold staining. These data were
      correlated with increased functional recovery of 6-OHDA-lesioned rats with
      preceding STN-lesioning. Here, we extend the previous study design to observation
      periods of up to 12 weeks to assess long-term effects. Furthermore, to elucidate
      cellular mechanisms underlying potential neuroprotective effects, we explore the
      regulation of cellular markers involved in neurodegenerative cascades via
      immunocytochemistry. We show that preceding STN-lesioning significantly inhibits
      6-OHDA induced expression/phosphorylation of the transcription factor c-Jun in
      surviving nigral neurons in comparison with controls. However, we also
      demonstrate that functionally neuroprotective effects of preceding STN-lesioning
      subside after 12 weeks, as assessed with TH immunostaining. We therefore conclude
      that c-Jun induction/phosphorylation is involved in 6-OHDA toxicity and that STN
      lesioning transiently preserves of dopaminergic phenotype of nigral neurons
      partially via delaying the induction and attenuating the expression and
      phosphorylation of c-Jun.

PMID- 16598704
TI  - Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in
      young rat offspring.
AB  - Clinical studies demonstrate that prenatal stress causes cognitive deficits and
      increases vulnerability to affective disorders in children and adolescents. The
      underlying mechanisms are not yet fully understood. Here, we reported that
      prenatal stress (10 unpredictable, 1 s, 0.8 mA foot shocks per day during
      gestational days 13-19) impaired long-term potentiation (LTP) but facilitated
      long-term depression (LTD) in hippocampal CA1 region in slices of the prenatal
      stressed offspring (5 weeks old). Cross-fostering neonate offspring by the
      prenatal stressed or control mothers did not change the effects of prenatal
      stress on the hippocampal LTP and LTD. Furthermore, prenatal stress enhanced the
      effects of acute stress on the hippocampal LTP and LTD and impaired spatial
      learning and memory in the Morris water maze in the young rat offspring.
      Therefore, prenatal stress alters synaptic plasticity and enhances the effects of
      acute stress on synaptic plasticity in the hippocampus, which may be the
      mechanism for the impaired spatial learning and memory in young rat offspring.

PMID- 16598705
TI  - Alterations of postsynaptic density proteins in the hippocampus of rat offspring
      from the morphine-addicted mother: Beneficial effect of dextromethorphan.
AB  - Infants passively exposed to morphine or heroin through their addicted mothers
      usually develop characteristic withdrawal syndrome of morphine after birth. In
      such early life, the central nervous system exhibits significant plasticity and
      can be altered by various prenatal influences, including prenatal morphine
      exposure. Here we studied the effects of prenatal morphine exposure on
      postsynaptic density protein 95 (PSD-95), an important cytoskeletal
      specialization involved in the anchoring of the NMDAR and neuronal nitric oxide
      synthase (nNOS), of the hippocampal CA1 subregion from young offspring at
      postnatal day 14 (P14). We also evaluated the therapeutic efficacy of
      dextromethorphan, a widely used antitussive drug with noncompetitive antagonistic
      effects on NMDARs, for such offspring. The results revealed that prenatal
      morphine exposure caused a maximal decrease in PSD-95 expression at P14 followed
      by an age-dependent improvement. In addition, prenatal morphine exposure reduced
      not only the expression of nNOS and the phosphorylation of cAMP responsive
      element-binding protein at serine 133 (CREB(Serine-133)), but also the magnitude
      of long-term depression (LTD) at P14. Subsequently, the morphine-treated
      offspring exhibited impaired performance in long-term learning and memory at
      later ages (P28-29). Prenatal coadministration of dextromethorphan with morphine
      during pregnancy and throughout lactation could significantly attenuate the
      adverse effects as described above. Collectively, the study demonstrates that
      maternal exposure to morphine decreases the magnitude of PSD-95, nNOS, the
      phosphorylation of CREB(Serine-133), and LTD expression in hippocampal CA1
      subregion of young offspring (e.g., P14). Such alterations within the developing
      brain may play a role for subsequent neurological impairments (e.g., impaired
      performance of long-term learning and memory). The results raise a possibility
      that postsynaptic density proteins could serve an important role, at least in
      part, for the neurobiological pathogenesis in offspring from the morphine
      addicted mother and provide tentative therapeutic strategy.

PMID- 16598706
TI  - A natural history model of stage progression applied to breast cancer.
AB  - Invasive breast cancer is commonly staged as local, regional or distant disease.
      We present a stochastic model of the natural history of invasive breast cancer
      that quantifies (1) the relative rate that the disease transitions from the
      local, regional to distant stages, (2) the tumour volume at the stage transitions
      and (3) the impact of symptom-prompted detection on the tumour size and stage of
      invasive breast cancer in a population not screened by mammography. By symptom
      prompted detection, we refer to tumour detection that results when symptoms
      appear that prompt the patient to seek clinical care. The model assumes
      exponential tumour growth and volume-dependent hazard functions for the times to
      symptomatic detection and stage transitions. Maximum likelihood parameter
      estimates are obtained based on SEER data on the tumour size and stage of
      invasive breast cancer from patients who were symptomatically detected in the
      absence of screening mammography. Our results indicate that the rate of symptom
      prompted detection is similar to the rate of transition from the local to
      regional stage and an order of magnitude larger than the rate of transition from
      the regional to distant stage. We demonstrate that, in the even absence of
      screening mammography, symptom-prompted detection has a large effect on reducing
      the occurrence of distant staged disease at initial diagnosis.

PMID- 16598707
TI  - Electron ionization-induced fragmentation of some new dibenzo(d, f)(1,3)dioxepine
      derivatives.
AB  - The mass spectrometric behaviour of a series of 6,6-disubstituted
      dibenzo(d,f)(1,3)dioxepine derivatives have been studied. The fragmentation
      patterns were described and discussed in detail with the aid of labelled
      compounds, accurate mass measurements and collisionally induced dissociation
      experiments performed using an ion trap.

PMID- 16598708
TI  - Characterization of metabolites of tanshinone IIA in rats by liquid
      chromatography/tandem mass spectrometry.
AB  - The metabolism of tanshinone IIA was studied in rats after a single-dose
      intravenous administration. In the present study, 12 metabolites of tanshinone
      IIA were identified in rat bile, urine and feces with two LC gradients using LC
      MS/MS. Seven phase I metabolites and five phase II metabolites of tanshinone IIA
      were characterized and their molecular structures proposed on the basis of the
      characteristics of their precursor ions, product ions and chromatographic
      retention time. The seven phase I metabolites were formed, through two main
      metabolic routes, which were hydroxylation and dehydrogenation metabolism. M1,
      M4, M5 and M6 were supposedly tanshinone IIB, hydroxytanshinone IIA,
      przewaquinone A and dehydrotanshinone IIA, respectively, by comparing their HPLC
      retention times and mass spectral patterns with those of the standard compounds.
      The five phase II metabolites identified in this research were all glucuronide
      conjugates, all of which showed a neutral loss of 176 Da. M9 and M12 were more
      abundant than other identified metabolites in the bile, which was the main
      excretion path of tanshinone IIA and the metabolites. M12 was the main metabolite
      of tanshinone IIA. M9 and M12 were proposed to be the glucuronide conjugates of
      two different semiquinones and these semiquinones were the hydrogenation products
      of dehydrotanshinone IIA and tanshinone IIA, respectively. This hydrogenized
      reaction may be catalyzed by the NAD(P)H: quinone acceptor oxidoreductase (NQO).
      The biotransformation pathways of tanshinone IIA were proposed on the basis of
      this research.

PMID- 16598709
TI  - Quantification of fudosteine in human plasma by high-performance liquid
      chromatography-electrospray ionization mass spectrometry employing precolumn
      derivatization with 9-fluorenylmethyl chloroformate.
AB  - This paper describes a novel method for the sensitive and selective determination
      of fudosteine in human plasma. The method involves a derivatization step with 9
      fluorenylmethyl chloroformate (FMOC-Cl) in borate buffer and detection based on
      high-performance liquid chromatography-electrospray ionization mass spectrometry
      (LC/ESI/MS). After acetonitrile-induced protein precipitation of plasma samples,
      fudosteine was derivatized with FMOC-Cl, then extracted by ethyl acetate,
      evaporated, reconstituted and injected using an LC/ESI/MS instrument. Separation
      was achieved using an ODS column and isocratic elution. Excellent linearity was
      obtained for the entire calibration range from 0.05 to 20 microg/ml. Validation
      assays of the lower limit of quantification (LLOQ) as well as for the intra- and
      inter-batch precision and accuracy met the international acceptance criteria for
      bioanalytical method validation. Using the developed analytical method,
      fudosteine could be detected for the first time in human plasma with a low limit
      of detection (LLOD) of 0.03 microg/ml. The proposed method has been successfully
      applied to study the pharmacokinetics of fudosteine in healthy Chinese volunteers
      after single and multiple oral administration.

PMID- 16598710
TI  - Dynamic changes in the direction of the theta rhythmic drive between
      supramammillary nucleus and the septohippocampal system.
AB  - Neurons in the supramammillary nucleus (SUM) of urethane-anesthetized rats fire
      rhythmically in synchrony with hippocampal theta rhythm. As these neurons project
      to the septum and hippocampus, it is generally assumed that their role is to
      mediate ascending activation, leading to the hippocampal theta rhythm. However,
      the connections between SUM and the septohippocampal system are reciprocal; there
      is strong evidence that theta remains in the hippocampus after SUM lesions and in
      the SUM after lesioning the medial septum. The present study examines the
      dynamics of coupling between rhythmic discharge in the SUM and hippocampal field
      potential oscillations, using the directionality information carried by the two
      signals. Using directed transfer function analysis, we demonstrate that during
      sensory-elicited theta rhythm and also during short episodes of theta
      acceleration of spontaneous oscillations, the spike train of a subpopulation of
      SUM neurons contains information predicting future variations in rhythmic field
      potentials in the hippocampus. In contrast, during slow spontaneous theta rhythm,
      it is the SUM spike signal that can be predicted from the preceding segment of
      the electrical signal recorded in the hippocampus. These findings indicate that,
      in the anesthetized rat, SUM neurons effectively drive theta oscillations in the
      hippocampus during epochs of sensory-elicited theta rhythm and short episodes of
      theta acceleration, whereas spontaneous slow theta in the SUM is controlled by
      descending input from the septohippocampal system. Thus, in certain states,
      rhythmically firing SUM neurons function to accelerate the septal theta
      oscillator, and in others, they are entrained by a superordinate oscillatory
      network.

PMID- 16598711
TI  - Characterization of partially folded intermediates of papain in presence of
      cationic, anionic, and nonionic detergents at low pH.
AB  - A systematic investigation of the effects of detergents [Sodium dodecyl sulphate
      (SDS), hexa decyltrimethyl ammonium bromide (CTAB) and Tween-20] on the structure
      of acid-unfolded papain (EC.3.4.22.2) was made using circular dichroism (CD),
      intrinsic tryptophan fluorescence, and 1-anilino 8-sulfonic acid (ANS) binding.
      At pH 2, papain exhibits a substantial amount of secondary structure and is
      relatively less denatured compared with 6 M GdnHCl (guanidine hydrochloride) but
      loses the persistent tertiary contacts of the native state. Addition of
      detergents caused an induction of alpha-helical structure as evident from the
      increase in the mean residue ellipticity value at 208 and 222 nm. Near-UV CD
      spectra also showed the regain of native-like spectral features in the presence
      of 8 mM SDS and 3.5 mM CTAB. Induction of structure in acid-unfolded papain was
      greater in the presence SDS followed by CTAB and Tween-20. Intrinsic tryptophan
      fluorescence studies indicate the change in the environment of tryptophan
      residues upon addition of detergents to acid-unfolded papain. Addition of 8 mM
      SDS resulted in the loss of ANS binding sites exhibited by a decrease in ANS
      fluorescence intensity, suggesting the burial of hydrophobic patches. Maximum ANS
      binding was obtained in the presence of 0.1 mM Tween-20 followed by CTAB,
      indicating a compact "molten-globule"-like conformation with enhanced exposure of
      hydrophobic surface area. Acid-unfolded papain in the presence of detergents
      showed the partial recovery of enzymatic activity. These results suggest that
      papain at low pH and in the presence of SDS exists in a partially folded state
      characterized by native-like secondary structure and tertiary folds. While in the
      presence of Tween, acid-unfolded papain exists as a compact intermediate with
      molten-globule-like characteristics, viz. enhanced hydrophobic surface area and
      retention of secondary structure. While in the presence of CTAB it exists as a
      compact intermediate with regain of native-like secondary and partial tertiary
      structure as well as high ANS binding with the partially recovered enzymatic
      activity, i.e., a molten globule state with tertiary folds.

PMID- 16598712
TI  - TGF beta-mediated RhoA expression is necessary for epithelial-mesenchymal
      transition in the embryonic chick heart.
AB  - Endothelia in the atrioventricular canal (AVC) of the embryonic heart undergo an
      epithelial-mesenchymal transition (EMT) and migrate into the underlying
      extracellular matrix. We explore here whether RhoA mediates this EMT. RhoA was
      detected in all cells of the chick heart during the stages studied. Expression
      was elevated when EMT was actively occurring. Explants treated with C3 exoenzyme
      in collagen gel cultures showed a significant decrease in mesenchymal cell
      numbers. siRNA was used to inhibit RhoA mRNA, and both activated endothelial and
      mesenchymal cells decreased significantly with treatment. Loss of RhoA produced a
      reduction of RhoB, cyclin-b2, and beta-catenin messages showing that these genes
      are regulated downstream of RhoA. In contrast, runx-2 was not reduced. Inhibition
      of TGFbeta3 or TGFbeta2 activity caused a large reduction of RhoA message. These
      data place RhoA in TGFbeta regulated pathways for both endothelial activation and
      mesenchymal invasion and demonstrate a functional requirement during EMT.

PMID- 16598713
TI  - Complementary expression pattern of Zfhx1 genes Sip1 and deltaEF1 in the mouse
      embryo and their genetic interaction revealed by compound mutants.
AB  - In mouse embryos, the Zfhx1 transcription factor genes, Sip1 and deltaEF1, are
      expressed in complementary domains in many tissues. Their possible synergism in
      embryogenesis was investigated by comparing the phenotype of Sip1-/-;deltaEF1-/-
      double homozygotes with single homozygous embryos. Unexpectedly, in Sip1-/-
      embryos deltaEF1 was ectopically activated, suggesting a negative regulation of
      deltaEF1 expression by Sip1. Sip1-/-;deltaEF1-/- embryos were similar to Sip1-/-
      embryos in short somite production and developmental arrest around E8.5, but
      showed more severe defects in dorsal neural tube morphogenesis accompanied by a
      larger reduction of Sox2 expression, ascribable to the loss of the ectopic
      deltaEF1 expression. Sip1+/-;deltaEF1-/- embryos develop various morphological
      defects after E10 that were absent in deltaEF1-/- embryos even in tissues without
      significant overlap of Sip1 and deltaEF1 expression, and arrested during mid
      gestation earlier than deltaEF1-/- embryos. These findings indicate that complex
      synergistic interactions occur between Zfhx1 transcription factor genes during
      mouse embryogenesis.

PMID- 16598714
TI  - Neuromuscular stimulation causes muscle phenotype-dependent changes in the
      expression of the IGFs and their binding proteins in developing slow and fast
      muscle of chick embryos.
AB  - Insulin-like growth factor (IGF) -1 and -2 and binding protein (IGFBP-2, -4, and 
      5) expression can be affected by several environmental factors, but the impact of
      movement on the IGF axis during late embryogenesis has yet to be fully
      characterized. Movement was promoted in chick embryos during mid-embryogenesis
      using 4-aminopyridine (4-AP). The results indicate an increase in IGF-1 (P <
      0.01) and a decrease in IGFBP-2 (P < 0.05) mRNA expression in slow muscle of the
      stimulated group compared with the control group. In fast muscle, there was a
      decrease in IGF-2 (P < 0.01) on embryonic day (ED) 16 and an increase in IGFBP-2
      (P < 0.01) and IGFBP-4 (P < 0.05) and in IGFBP-5 (P < 0.05) expression on ED18 in
      the stimulated group compared with the control group. These results indicate that
      neuromuscular stimulation with 4-AP influences IGF axis gene expression in a
      muscle fiber type-dependent manner. Consequences of the changes in the IGF system
      for each muscle are discussed.

PMID- 16598716
TI  - 21st century neontology and the comparative development of the vertebrate skull.
AB  - Classic neontology (comparative embryology and anatomy), through the application
      of the concept of homology, has demonstrated that the development of the
      gnathostome (jawed vertebrate) skull is characterized both by a fidelity to the
      gnathostome bauplan and the exquisite elaboration of final structural design.
      Just as homology is an old concept amended for modern purposes, so are many of
      the questions regarding the development of the skull. With due deference to
      Geoffroy-St. Hilaire, Cuvier, Owen, Lankester et al., we are still asking: How
      are bauplan fidelity and elaboration of design maintained, coordinated, and
      modified to generate the amazing diversity seen in cranial morphologies? What
      establishes and maintains pattern in the skull? Are there universal developmental
      mechanisms underlying gnathostome autapomorphic structural traits? Can we detect
      and identify the etiologies of heterotopic (change in the topology of a
      developmental event), heterochronic (change in the timing of a developmental
      event), and heterofacient (change in the active capacetence, or the elaboration
      of capacity, of a developmental event) changes in craniofacial development within
      and between taxa? To address whether jaws are all made in a like manner (and if
      not, then how not), one needs a starting point for the sake of comparison. To
      this end, we present here a "hinge and caps" model that places the articulation,
      and subsequently the polarity and modularity, of the upper and lower jaws in the
      context of cranial neural crest competence to respond to positionally located
      epithelial signals. This model expands on an evolving model of polarity within
      the mandibular arch and seeks to explain a developmental patterning system that
      apparently keeps gnathostome jaws in functional registration yet tractable to
      potential changes in functional demands over time. It relies upon a system for
      the establishment of positional information where pattern and placement of the
      "hinge" is driven by factors common to the junction of the maxillary and
      mandibular branches of the first arch and of the "caps" by the signals emanating
      from the distal-most first arch midline and the lamboidal junction (where the
      maxillary branch meets the frontonasal processes). In this particular model, the
      functional registration of jaws is achieved by the integration of "hinge" and
      "caps" signaling, with the "caps" sharing at some critical level a developmental
      history that potentiates their own coordination. We examine the evidential
      foundation for this model in mice, examine the robustness with which it can be
      applied to other taxa, and examine potential proximate sources of the signaling
      centers. Lastly, as developmental biologists have long held that the anterior
      most mesendoderm (anterior archenteron roof or prechordal plate) is in some way
      integral to the normal formation of the head, including the cranial skeletal
      midlines, we review evidence that the seminal patterning influences on the early
      anterior ectoderm extend well beyond the neural plate and are just as important
      to establishing pattern within the cephalic ectoderm, in particular for the
      "caps" that will yield medial signaling centers known to coordinate jaw
      development.

PMID- 16598715
TI  - Molecular genetic cascades for external genitalia formation: an emerging
      organogenesis program.
AB  - External genitalia are anatomical structures located at the posterior embryonic
      region as part of several urogenital/reproductive organs. The embryonic anlage of
      the external genitalia, the genital tubercle (GT) develops as a bud-shaped
      structure with an initial urethral plate and later urethra. Embryonic external
      genitalia are considered to be one of the appendages. Recent experiments suggest
      that essential regulatory genes possess similar functions for the outgrowth
      regulation of the GT and limb appendages. The transient embryonic epithelia
      located in the distal GT are called the distal urethral epithelium (DUE)
      regulating, at least in part, the (distal) GT development. This review covers the
      available data about early patterning of GT and discusses the molecular
      developmental similarities and points of divergence between the different
      appendages. Development of the male and female external genitalia is also
      reviewed.

PMID- 16598717
TI  - Bolus delay and dispersion in perfusion MRI: implications for tissue predictor
      models in stroke.
AB  - Perfusion maps, which are calculated from dynamic-susceptibility contrast (DSC)
      MRI data by deconvolution of the arterial input function (AIF), are commonly used
      to predict tissue infarction in acute stroke. However, since the AIF is commonly
      measured in a major artery, there can be perfusion measurement errors associated
      with bolus delay/dispersion. Although methods to account for delay-related errors
      have been proposed, the effect of dispersion is more difficult to deal with and
      is usually left uncorrected. This study presents an assessment of the delay
      dispersion relationship in a group of patients. Although a significant
      correlation was observed with one of the bolus delay definitions used, the
      estimation of the dispersion from the degree of delay was unreliable.
      Importantly, the dispersion observed in many patients was sufficient to result in
      substantial perfusion errors. The results are compared with previous numerical
      simulations, and their implications for the assessment and management of acute
      stroke are discussed.

PMID- 16598718
TI  - Changing body temperature affects the T2* signal in the rat brain and reveals
      hypothalamic activity.
AB  - This study was designed to determine brain activity in the hypothalamus-in
      particular the thermoregulatory function of the hypothalamic preoptic area (PO).
      We experimentally changed the body temperature in rats within the physiological
      range (37-39 degrees C) and monitored changes in blood oxygenation level
      dependent (BOLD) MR signal. To explore PO activity we had to deal with general
      signal changes caused by temperature-dependent alterations in the affinity of
      oxygen for hemoglobin, which contributes to BOLD contrast because it is partly
      sensitive to the amount of paramagnetic deoxyhemoglobin in the voxel. To reduce
      these overall temperature-induced effects, we corrected the BOLD data using brain
      specific correction algorithms. The results showed activity of the PO during body
      warming from 38 degrees C to 39 degrees C, supported by an increased BOLD signal
      after correction. This is the first fMRI study on the autonomous nervous system
      in which hypothalamic activity elicited by changes in the internal environment
      (body temperature) was monitored. In this study we also demonstrate 1) that any
      fMRI study of anesthetized small animals should guard against background BOLD
      signal drift, since animals are vulnerable to body temperature fluctuations; and
      2) the existence of a link between PO activity and the sympathetically-mediated
      opening of the arteriovenous anastomoses in a parallel study on the rat tail, a
      peripheral thermoregulatory organ.

PMID- 16598719
TI  - Fast spin echo sequences with very long echo trains: design of variable
      refocusing flip angle schedules and generation of clinical T2 contrast.
AB  - Reducing and continuously varying the flip angle of the refocusing RF pulses in a
      rapid acquisition with relaxation enhancement (RARE; fast/turbo spin echo)
      sequence is a useful means of addressing high RF power deposition and modulation
      transfer function (MTF) distortion due to relaxation. This work presents a
      streamlined technique to generate a sequence of refocusing flip angles on a per
      prescription basis that produces relatively high SNR and limits blurring in a
      wide range of materials encountered in vivo. Since the "effective TE"
      (traditionally defined as the time at which the center of k-space is sampled) no
      longer corresponds to the expected amount of spin-echo T2 contrast due to the
      mixing of stimulated and spin echoes, a "contrast-equivalent" TE is defined and
      experimentally demonstrated that allows annotation of a more accurate effective
      TE that matches the contrast produced by 180 degrees refocusing. Furthermore,
      contrast is shown to be manipulable by the addition of magnetization preparation
      pulse sequence segments, such as T2-prep, to produce clinically desirable
      contrast for routine head and body imaging.

PMID- 16598720
TI  - Inversion recovery radial MRI with interleaved projection sets.
AB  - The radial trajectory has found applications in cardiac imaging because of its
      resilience to undersampling and motion artifacts. Recent work has shown that
      interleaved and weighted radial imaging can produce images with multiple
      contrasts from a single data set. This feature was investigated for inversion
      recovery imaging of scar using a radial technique. The 2D radial imaging method
      was modified to acquire quadruply interleaved projection sets within each
      acquisition window of the cardiac cycle. These data were reconstructed using k
      space weightings that used a smaller segment of the acquisition window for the
      central k-space data, the determinant of image contrast. This method generates
      four images with different T1 weightings. The novel approach was compared with
      noninterleaved radial imaging, interleaved radial without weightings, and
      Cartesian imaging in simulations, phantoms, and seven subjects with clinical
      myocardial infarction. The results show that during a typical acquisition window
      after an inversion pulse, magnetization changes rapidly. The interleaved
      acquisition provided better image quality than the noninterleaved radial
      acquisition. Interleaving with weighting provided better quality when the
      inversion time (TI) was shorter than optimal; otherwise, interleaving without
      weighting was superior. These methods enable a radial trajectory to be employed
      in conjunction with preparation pulses for viability imaging.

PMID- 16598721
TI  - Methionine-dependence phenotype of tumors: metabolite profiling in a melanoma
      model using L-[methyl-13C]methionine and high-resolution magic angle spinning 1H
      13C nuclear magnetic resonance spectroscopy.
AB  - Tumors frequently have abnormal L-methionine (Met) metabolism, the so-called Met
      dependence phenotype that refers to the inability to proliferate in the absence
      of Met. However, the origin of this phenotype is still unknown and may arise from
      one of several pathways of Met metabolism. To help characterize the metabolic
      features of Met-dependent/independent phenotypes, the fate of the methyl carbon
      of L-[methyl-13C]Met was chased in a murine model of malignant melanoma (B16-F1)
      in vitro and in vivo. Growth curves under Met restriction showed that melanoma
      cells in vitro were Met-independent, whereas implanted melanoma tumors in vivo
      were Met-dependent. Label-assisted high-resolution magic angle spinning 1H-13C
      NMR spectroscopy metabolite profiling showed that, in vitro, creatine and
      phosphatidylcholine 13C-enrichments were poor, but S-adenosyl-Met and
      posttranslationally N-methylated protein signals were strong. In contrast, in
      vivo, creatine and phosphatidylcholine enrichments were strong but S-adenosyl-Met
      and N-methylated protein signals were poor. In addition, in vivo,
      transsulfuration was very efficient, consumed one-carbon units originating from
      the methyl carbon of Met, and yielded taurine labeling. From these data, the Met
      dependent/independent phenotypes appear closely related to the source of one
      carbon units. Thus, L-[methyl-13C]Met-assisted NMR spectroscopy metabolite
      profiling allowed the discrimination between Met-dependence and Met-independence
      and provided novel mechanistic information on their origin.

PMID- 16598723
TI  - Continuously moving table 3D MRI with lateral frequency-encoding direction.
AB  - A method is presented for 3D MRI in an extended field of view (FOV) based on
      continuous motion of the patient table and an efficient acquisition scheme. A
      gradient-echo MR pulse sequence is applied with lateral (left-right (L/R))
      frequency-encoding direction and slab selection along the direction of motion.
      Compensation for the table motion is achieved by a combination of slab tracking
      and data alignment in hybrid space. The method allows fast k-space coverage to be
      achieved, especially when a short sampling FOV is chosen along the direction of
      table motion, as is desirable for good image quality. The method can be
      incorporated into different acquisitions schemes, including segmented k-space
      scanning, which allows for contrast variation with the use of magnetization
      preparation. Head-to-toe images of volunteers were obtained with good quality
      using 3D spoiled gradient-echo sequences. As an example of magnetization-prepared
      imaging, fat/water separated images were acquired using chemical shift selective
      (CHESS) presaturation pulses.

PMID- 16598724
TI  - Partial-k-space acquisition method for improved SNR efficiency and temporal
      resolution in 3D fMRI.
AB  - Previous studies have shown the relative importance of physiological noise and
      thermal noise in 2D MR images. Since physiological noise is proportional to the
      signal, it can be the dominant component at the center of k-space. In this study
      we demonstrate that the signal-to-noise ratio (SNR) efficiency and temporal
      resolution for 3D functional MRI (fMRI) are increased by the use of a partial-k
      space acquisition method. In partial-k-space methods, the high-spatial-frequency
      components are doubled in amplitude during reconstruction, resulting in twice as
      much noise from those components. However, in sum these contributions are
      relatively small compared to those at the low spatial frequencies, where
      physiological noise is dominant. Therefore, the effect on the final MR images is
      almost negligible due to the square summation rule. Thus, the partial-k-space 3D
      method sacrifices much less SNR than is expected from the thermal noise model,
      and the SNR efficiency is increased compared to a full-k-space acquisition since
      more time frames can be collected for the same scan time. Accordingly, the
      temporal resolution can be increased in 3D acquisitions because only partial
      coverage of k-space is necessary. Experimental results confirm that more
      activation with a higher average t-score is detected by this method.

PMID- 16598725
TI  - Simultaneous outer volume and blood suppression by quadruple inversion-recovery.
AB  - A new method has been developed for reduced field-of-view (FOV) imaging with
      simultaneous blood suppression. This method combines suppression of signals from
      the outer volume and inflowing blood by using a small-FOV quadruple inversion
      recovery (SFQIR) preparative pulse sequence consisting of two double-inversion
      pulse pairs separated by appropriate delays. Within each pair, inversion pulses
      are successively applied to the imaged slice and the slab orthogonal to the
      imaging plane with the thickness equal to the FOV size in the phase-encoding
      direction. Each double inversion results in the reinversion of the magnetization
      in the central part of the FOV, while the outer areas of the FOV and inflowing
      blood remain inverted. The SFQIR module was implemented for single- and
      multislice acquisition with a fast spin-echo readout sequence. Based on a
      theoretical model of the signal, the timing parameters of the sequence
      corresponding to the maximal suppression efficiency can be found by minimizing
      the variation of the normalized signal over the entire range of T1's that occur
      in tissues. The method was tested for black-blood imaging of the aorta and
      carotid arteries, and the results demonstrated its ability to eliminate motion
      and flow artifacts, reduce scan time, and improve spatial resolution.

PMID- 16598726
TI  - MR susceptometry for measuring global brain oxygen extraction.
AB  - Monitoring of oxygen saturation in jugular venous blood gives an estimate of the
      balance of global oxygen delivery and cerebral oxygen consumption. We present a
      noninvasive approach to measure oxygen saturation in vivo in the internal jugular
      vein using MR susceptometry by exploiting the characteristic susceptibility of
      deoxyhemoglobin, and demonstrate the feasibility of performing such measurements
      in a group of subjects. We assessed the sensitivity of the method for detecting
      small changes in oxygen saturation by monitoring the variations observed during
      breath-holding and hypoventilation experiments. Unlike alternative methods, the
      susceptometric technique does not require calibration.

PMID- 16598727
TI  - Bioactivation of a cobalt alloy by coating with wollastonite during investment
      casting.
AB  - Cobalt alloy samples were bioactivated during investment casting. The cavities of
      the investment mold were previously coated with wollastonite. Additionally,
      before coating with wollastonite, some mold cavities were filled out with
      graphite rods to avoid a chemical reaction between the wollastonite powder and
      the investment material. Half of the cast samples were heat treated at 1220
      degrees C for 1 h. To perform the in vitro bioactivity assessment, the cast and
      heat-treated samples were immersed in a simulated body fluid solution (SBF) for a
      period of 21 days. The surface of the samples before and after immersion in SBF
      was characterized by SEM, EDX, and XRD analyses. During the casting, particles of
      pseudowollastonite were embedded on the metallic surface. After immersion of the
      samples in SBF, a ceramic layer was formed on both the alloy obtained by using
      the investment mold and the alloy obtained by using the graphite-filled cavity.
      The ceramic layer was thicker on the alloy cast in the investment mold. The layer
      was identified as hydroxyapatite by XRD analysis, in all the cases. The heat
      treated samples after immersion in SBF showed the formation of a thin homogeneous
      layer consisting of fine grains of apatite.

PMID- 16598728
TI  - Respiration-induced B0 field fluctuation compensation in balanced SSFP: real-time
      approach for transition-band SSFP fMRI.
AB  - In functional MRI (fMRI) the resonance frequency shift induced from respiration
      is a major source of physiological noise. In transition-band SSFP fMRI the
      respiration-induced resonance offset not only increases noise interference, it
      also shifts the activation band. This leads to a reduction in the contrast-to
      noise ratio (CNR) and the potential for varying contrast levels during the
      experiment. A novel real-time method that compensates for the respiration-induced
      resonance offset frequency is presented. This method utilizes free induction
      decay (FID) phase information to measure the resonance offset. For compensation,
      one can update the resonant frequency in real time by changing the transmit RF
      pulse and receiver phases to track the measured offset. The results show
      decreased signal power in the respiration frequency band and increased numbers of
      activated voxels with higher Z-scores compared to uncompensated experiments.

PMID- 16598729
TI  - MRI analysis of angiogenesis during mouse embryo implantation.
AB  - Uterine receptivity and embryo implantation depend on local induction of
      angiogenesis and vascular permeability. Poor uterine receptivity has been
      implicated in implantation failure; however, relatively little is known about the
      mechanism that underlies endometrial vascular hyperpermeability in implantation
      sites. Here we show that contrast-enhanced (CE)-MRI and fluorescence microscopy
      using biotin-BSA-GdDTPA allowed high-resolution detection and quantitative
      assessment of mouse embryo implantation sites as early as embryonic day 4.5
      (E4.5), and subsequent vascular expansion at E5.5. Vessel permeability, but not
      blood volume, was significantly elevated in E4.5 implantation sites relative to
      nonimplanted uterus, showing that elevation of vascular permeability is a very
      early response preceding E4.5. A significantly increased blood volume was
      detected by MRI and fluorescence microscopy in implantation sites between E4.5
      and E5.5. On the other hand, despite the increase in blood volume, implantation
      sites showed only a small nonsignificant further increase in vascular
      permeability during these 2 days, demonstrating the rapid dynamics of vascular
      remodeling during the early days of pregnancy. Functional imaging by MRI, as
      reported here, allows multiparametric measurement of angiogenesis during normal
      mouse implantation and would facilitate the application of MRI to evaluate
      involvement of the vasculature in mouse models of impaired implantation.

PMID- 16598730
TI  - The immunosuppressant mycophenolate mofetil improves preservation of the
      perforant path in organotypic hippocampal slice cultures: a retrograde tracing
      study.
AB  - Previous studies with excitotoxically lesioned organotypic hippocampal slice
      cultures (OHSC) have revealed that the immunosuppressant mycophenolate mofetil
      (MMF) inhibits microglial activation and suppresses neuronal injury in the
      dentate gyrus. We here investigate whether MMF also has beneficial effects on
      axon survival in a long-range projection, the perforant path. Complex OHSC
      including the entorhinal cortex were obtained from Wistar rats (p8); the plane of
      section ensuring that perforant path integrity was preserved. These preparations
      were cultured for 9 days in vitro with or without MMF (100 microg/ml). After
      fixation, the perforant path was retrogradely labeled by application of the
      fluorescent dye DiI (1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine) in
      the hilus of the dentate gyrus, and neuronal perikarya were immunohistochemically
      stained by the neuron-specific marker NeuN. Analysis of DiI-labeled and NeuN
      stained OHSC by confocal laser scanning microscopy revealed double-labeled
      neurons in the entorhinal cortex, which projected to the dentate gyrus via the
      perforant path. Quantitative analysis showed that the number of these double
      labeled neurons was 19-fold higher in OHSC treated with MMF than in control
      cultures (P < 0.05). Our findings indicate that MMF treatment improves
      preservation of the perforant path and encourage further studies on development
      and regeneration of long-range projections under the influence of
      immunosuppressants.

PMID- 16598731
TI  - Combo acquisitions: balancing scan time reduction and image quality.
AB  - Recently a new technique for the combined acquisition of multicontrast images,
      termed "combo acquisition," was introduced. In combo acquisitions, the three
      concepts of 1) variable acquisition parameters, 2) k-space data sharing, and 3)
      multicontrast imaging are systematically integrated to reduce MRI scan time and
      improve data utilization in a clinical setting. In this study, two-contrast and
      three-contrast spin-echo (SE) and turbo spin-echo (TSE) combo acquisition
      protocols that were designed and optimized in simulation experiments were
      implemented on a 1.5 T clinical scanner. Phantom and human brain data from
      volunteers and patients were acquired. Scan time reductions of 25-52% were
      achieved compared to standard acquisitions, largely confirming the simulation
      results. We evaluated the resulting images by quantitatively analyzing the
      preservation of contrast and the signal-to-noise ratio (SNR). In addition, data
      sets for 10 clinical cases obtained with TSE combo and corresponding standard
      acquisitions were graded by two experienced neuroradiologists in terms of the
      level of artifacts and image quality for comparison. Only minor image degradation
      with the combo scans was observed, indicating an inherent trade-off between scan
      time reduction and image quality. The specific aspects of combo acquisitions with
      respect to motion, flow, and k-space data weighting are discussed.

PMID- 16598732
TI  - Liposome-enhanced MRI of neointimal lesions in the ApoE-KO mouse.
AB  - Conventional high-resolution MRI is capable of detecting lipid-rich
      atherosclerotic plaques in both human atherosclerosis and animal models of
      atherosclerosis. In this study we induced neointimal lesions in ApoE-KO mice by
      placing a constrictive collar around the right carotid artery. The model was
      imaged with conventional multispectral MRI, and the thickened wall could not be
      distinguished from surrounding tissue. We then tested paramagnetic liposomes
      (mean size=90 nm) for their ability to improve MRI visualization of induced
      thickening, using Gd-DTPA as a control. T1-weighted (T1-w), black-blood MRI of
      the neck area of the mice was performed before and 15 min, 45 min, and 24 hr
      after intravenous injection of either paramagnetic liposomes or Gd-DTPA. The
      collared vessel wall of mice that were injected with liposomes showed a
      pronounced signal enhancement of approximately 100% immediately after injection,
      which was sustained largely until 24 hr postinjection. In contrast, the vessel
      wall of all controls (left carotid artery and animals injected with Gd-DTPA) did
      not show significant contrast enhancement at those time points. This study
      demonstrates that intimal thickening in ApoE-KO mice can be effectively detected
      by contrast-enhanced (CE)-MRI upon injection of paramagnetic liposomes.

PMID- 16598733
TI  - Measurement of kinetic parameters in skeletal muscle by magnetic resonance
      imaging with an intravascular agent.
AB  - The purpose of this work was to investigate the use of an intravascular contrast
      agent to determine perfusion kinetics in skeletal muscle. A two-compartment
      kinetic model was used to represent the flux of contrast agent between the
      intravascular space and extravascular extracellular space (EES). The relationship
      between the image signal-to-noise ratio (SNR) and errors in estimating
      permeability surface area product (Ktrans), interstitial volume (ve), and plasma
      volume (vp) for linear and nonlinear curve-fitting methods was estimated from
      Monte Carlo simulations. Similar results were obtained for both methods. For an
      image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%,
      respectively. In vivo experiments were conducted in rabbits to examine
      physiological differences between these parameters in the soleus (SOL) and
      tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were
      significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were
      values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles
      (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results
      demonstrate that relevant physiological metrics can be calculated in skeletal
      muscle using MRI with an intravascular contrast agent.

PMID- 16598734
TI  - The Noggin null mouse phenotype is strain dependent and haploinsufficiency leads
      to skeletal defects.
AB  - Noggin is a secreted peptide that binds and inactivates Bone Morphogenetic
      Proteins, members of the transforming growth factor beta superfamily of secreted
      signaling molecules. In vertebrate limbs, Noggin is expressed in condensing
      cartilage and immature chondrocytes. Inactivation of the Noggin gene has been
      reported in an inbred 129X1/SvJ mouse genetic background. The null allele was
      lethal at 18.5 dpc and resulted in severe hyperplasia of the cartilage together
      with multiple joint fusions. In order to investigate the effect of the genetic
      background on the phenotypic manifestation of Noggin inactivation, we crossed the
      Noggin null allele into the outbred CD1 and inbred DBA1 and C57BL/6 mouse
      strains. We describe here skeletal phenotypes of Noggin null mice, such as
      accelerated or delayed mineralization of different bones suggestive of a complex
      tissue response to the perturbations in BMP balances. Additionally, we found that
      in the absence of Noggin, early specification of myogenic differentiation was
      unaffected, whereas terminal stages of myogenesis were delayed. Furthermore, we
      have discovered Noggin haploinsufficiency leading to carpal and tarsal fusions
      reminiscent of some phenotypes reported for NOGGIN haploinsufficiency in humans.

PMID- 16598735
TI  - Toward quantitative short-echo-time in vivo proton MR spectroscopy without water
      suppression.
AB  - A methodological development for quantitative short-echo-time (TE) in vivo proton
      MR spectroscopy (MRS) without water suppression (WS) is described that integrates
      experimental and software approaches. Experimental approaches were used to
      eliminate frequency modulation sidebands and first-order phase errors. The
      dominant water signal was modeled and extracted by the matrix pencil method (MPM)
      and was used as an internal reference for absolute metabolite quantification.
      Spectral fitting was performed by combining the baseline characterization by a
      wavelet transform (WT)-based technique and time-domain (TD) parametric spectral
      analysis using full prior knowledge of the metabolite model spectra. The model
      spectra were obtained by spectral simulation instead of in vitro measurements.
      The performance of the methodology was evaluated by Monte Carlo (MC) studies,
      phantom measurements, and in vivo measurements on rat brains. More than 10
      metabolites were quantified from spectra measured at TE = 20 ms on a 4.7 T
      system.

PMID- 16598736
TI  - Measurement of brain glutamate and glutamine by spectrally-selective refocusing
      at 3 Tesla.
AB  - A new single-voxel proton NMR spectrally-selective refocusing method for
      measuring glutamate (Glu) and glutamine (Gln) in the human brain in vivo at 3T is
      reported. Triple-resonance selective 180 degrees RF pulses with a bandwidth of 12
      Hz were implemented within point-resolved spectroscopy (PRESS) for selective
      detection of Glu or Gln, and simultaneous acquisition of creatine singlets for
      use as a reference in phase correction. The carriers of the spectrally-selective
      180 degrees pulses and the echo times (TEs) were optimized with both numerical
      and experimental analyses of the filtering performance, which enabled
      measurements of the target metabolites with negligible contamination from N
      acetylaspartate and glutathione. The concentrations of Glu and Gln in the
      prefrontal cortex were estimated to be 9.7+/-0.5 and 3.0+/-0.7 mM (mean+/-SD,
      N=7), with reference to Cr at 8 mM.

PMID- 16598737
TI  - Mutation screening and association study of the candidate prostate cancer
      susceptibility genes MSR1, PTEN, and KLF6.
AB  - BACKGROUND: MSR1, PTEN, and KLF6 have been implicated as candidate susceptibility
      genes for prostate tumorigenesis. METHODS: Three hundred Jewish prostate cancer
      patients were screened for alterations in these genes. RESULTS: MSR1 was
      conserved in all patients. PTEN screening revealed a novel missense mutation and
      a silent change. Five KLF6 alterations were detected in 17 patients, including
      Q160X, the only nonsense KLF6 germline mutation described to date in a cancer
      patient. The KLF6 IVS1-27G>A polymorphism, recently associated with prostate
      cancer risk, was detected in 11.9% of the patients and 17.3% of the controls (P =
      0.043). IVS1-27A allele frequency was significantly lower in prostate cancer
      patients (P = 0.030), specifically in Ashkenazi patients (P = 0.047) compared to
      controls. CONCLUSIONS: We found no evidence that MSR1 and PTEN germline mutations
      are associated with prostate cancer risk in Jews. The negative association
      between KLF6 IVS1-27A and prostate cancer risk supports a population-specific
      effect of susceptibility alleles in prostate tumorigenesis.

PMID- 16598738
TI  - The distribution of serum prostate-specific antigen levels among American men:
      implications for prostate cancer prevalence and screening.
AB  - BACKGROUND: The purpose of this study was to describe the distribution of serum
      prostate-specific antigen (PSA) among American men and to estimate the number of
      prevalent cases of biopsy detectable prostate cancer among men with normal serum
      PSA. METHODS: We analyzed data of the National Health and Nutrition Examination
      Survey 2001-2002 (NHANES 2001-2002) data and combined these results with
      published data from the Prostate Cancer Prevention Trial (PCPT). RESULTS: Most
      men in the US have a serum PSA < or = 4.0 ng/ml, and mean and median serum PSA
      values rise steadily with age. There are an estimated 1,607,585 (95% CI 1,370,848
      1,844,322) prevalent cases of biopsy detectable prostate cancer in men aged 62-85
      years with a serum PSA < or = 4 ng/ml. Among men aged 62-75 years, there are an
      estimated 1,252,143 (95% CI 1,054,677-1,449,609) prevalent cases, including an
      estimated 195,499 (95% CI 140,234-250,764) high-grade tumors. CONCLUSION: A large
      number of prevalent cases of biopsy detectable prostate cancer exist in American
      men with a normal PSA.

PMID- 16598740
TI  - Fast and novel purification method to obtain the prostate specific antigen (PSA)
      from human seminal plasma.
AB  - BACKGROUND: Prostate specific antigen (PSA) is a relevant antigen in diagnosis;
      follow-up, and therapeutic approaches for fighting the prostate cancer. Several
      methods have been published previously to obtain a high purity preparation of
      PSA. In general, these methods are expensive, time-consuming, laborious, and in
      some cases produce low yields. METHODS: Based on a panel of 7 anti-PSA Mab's we
      carried on binding and elution experiments of PSA antigen in 96-well plates. The
      selected Mab were immobilized in a Sepharose CL-4B activated matrix with the
      purpose of purify PSA from human seminal fluid. In order to optimize the
      purification procedure, we test several washing and elution conditions
      (chaotropic agents, high ionic strength solution, and extreme pH). RESULTS: We
      selected a high ionic strength solution (2 M MgCl2) as elution condition, and a
      previous washing step with a mix of two ionic solutions (2.5 M NaCl pH 8/1 M
      MgCl2 pH 5.5) in order to purify PSA. Using such conditions we obtained a PSA
      preparation with 90% of purity and 50% of recovery. CONCLUSION: In this article,
      we report a simple, quickly, and non-expensive procedure to obtain free-PSA from
      human seminal plasma at high purity levels.

PMID- 16598739
TI  - Characterization of ZAG protein expression in prostate cancer using a semi
      automated microscope system.
AB  - OBJECTIVE: Zinc-alpha-2-glycoprotein 1 (ZAG) is a 41-kD secreted protein that is
      known to stimulate lipid degradation in adipocytes. The aim of this study was to
      determine how ZAG protein expression is associated with prostate cancer (PCa).
      MATERIALS AND METHODS: An immunohistochemistry analysis was performed on a 227
      PCa tissue microarray cases. ZAG protein expression was assessed using a semi
      automated cellular image analysis system. RESULTS: ZAG expression was associated
      with tumor stage (pT2 > pT3 > metastasis cases, P < 0.001), and was inversely
      associated with Gleason score on pathology (P = 0.01). ZAG intensity was
      predictive of biochemical recurrence (P = 0.002). On multivariate analysis
      including pT2 patients, the predictive factors of biochemical recurrence were ZAG
      expression (P = 0.016), Gleason score (P = 0.011), and surgical margin status (P
      = 0.047). CONCLUSIONS: This study characterized ZAG protein expression in PCa
      using a semi-automated system. ZAG expression level found to have an independent
      prognostic value for pT2 patients.

PMID- 16598742
TI  - Impact of model for end-stage liver disease (MELD) scoring system on pathological
      findings at and after liver transplantation.
AB  - The Model for End-Stage Liver Disease (MELD) scoring system, a validated
      objective liver disease severity scale, was adopted in February 2002 to allocate
      cadaveric organs for liver transplantation (LT). To improve transplantability
      before succumbing to advanced disease, patients with low-stage hepatocellular
      carcinoma (HCC) are given extra points in this system commensurate with their
      predicted mortality. Our aims were to determine 1) any change in the pathological
      findings at LT following the implementation of this system and 2) the impact of
      scoring advantage given to early-stage HCC. Clinicopathologic findings were
      compared before (pre-MELD, n = 87) and after (MELD, n = 58) the introduction of
      the MELD system. The findings in the pre-MELD vs. MELD groups were as follows:
      HCC, 27.5% vs. 48.3% (P = 0.001); portal vein thrombosis (PVT), 13.7% vs. 25.9%
      (P = 0.08); cholestasis, 16.1% vs. 32.7% (P = 0.026); inflammation grade of 2 or
      more, 43.7% vs. 48.3% (P = not significant); hepatitis C (HCV), 45.9% vs. 51.7%
      (P = not significant); HCV with lymphoid aggregates, 25% vs. 60% (P = 0.003); HCV
      with hyperplastic hilar nodes, 15.0% vs. 36.6% (P = 0.001); and post-LT HCC
      recurrence, 4.1% vs. 3.4% (P = not significant). Non-HCC-related findings were
      further compared in the 2 subgroups of pre-MELD (n = 57) and MELD (n = 31) after
      exclusion of HCC and fulminant hepatic failure (FHF) cases, and only cholestasis
      was significantly increased in the subgroup MELD. In conclusion, increased
      incidence of native liver cholestasis in the MELD era may be the histologic
      correlate of clinically severe liver disease. The scoring advantage given to low
      stage HCC did result in a significantly increased incidence of HCC in the MELD
      group, but it did not adversely affect the post-LT recurrence rate.

PMID- 16598741
TI  - Characterization of the mitochondrial aconitase promoter and the identification
      of transcription factor binding.
AB  - BACKGROUND: Mitochondrial (m) aconitase plays an important role in the unique
      pathway of citrate accumulation in prostate epithelial cells through its limited
      activity. In the current study, we characterized the human m-aconitase gene
      promoter. METHODS: A 1,411-bp 5'-flanking fragment of the human m-aconitase gene
      was cloned, followed by 5' serial deletion analysis of promoter activity.
      Transcriptional start sties and transcription factors bound to the promoter were
      identified by 5' RACE, DNA pull-down assay and transcription factor array
      analysis. RESULTS: Two transcriptional start sites were identified. The promoter
      fragment pulled down 15 transcription factors, some without consensus sequences
      in the promoter. Deletion of one Sp1 site eliminated all promoter activity.
      CONCLUSIONS: The m-aconitase promoter is contained in a 153-bp 5' fragment
      lacking a TATA or CAAT sequence. Sp1 binding to a specific Sp1 site is required
      for promoter activity while other transcription factors are recruited through
      protein-protein interactions.

PMID- 16598743
TI  - Interactions of B16F10 melanoma cells aggregated on a cellulose substrate.
AB  - There is evidence that the shape of cells and their contact with a matrix direct
      the growth and the differentiation of both normal and cancer cells. Cells in 3D
      culture resemble the in vivo situation more closely than do those in conventional
      2D cultures. We have studied the interactions and functions of B16F10 mouse
      melanoma cells, which spread and grow well on tissue culture polystyrene (tPS),
      when they were made to aggregate on cellulose-coated Petri dishes (CEL). This
      aggregation of melanoma cells on CEL was Ca2+ dependent and mediated by N
      cadherins. The levels of N-cadherin and beta-catenin transcripts in cells
      cultured on CEL and tPS were similar, but those on CEL contained less beta
      catenin protein. Immunoprecipitation and immunostaining showed that both N
      cadherins and beta-catenins were present at the membranes of cells on CEL. Cells
      proliferated significantly more slowly after 48 h on CEL and the cellulose
      coating caused most of them to arrest in G1. We also compared the melanin
      contents and tyrosinase activity of cells on CEL and controls grown on tPS.
      Melanogenesis was induced in cells aggregated on CEL. A cellulose substrate thus
      appears to be an outstanding tool for studying cell-cell interactions and cell
      functions in 3D cultures.

PMID- 16598744
TI  - Epigenetic modifications in osteogenic differentiation and transformation.
AB  - Almost all tumors are characterized by both architectural and cellular
      abnormalities in differentiation. Osteoblast development is relatively well
      understood, making osteosarcoma a good model for understanding how tumorigenesis
      perturbs normal differentiation. We argue that there are two key transition
      points in normal cellular differentiation that are the focus of oncogenic events,
      in both of which epigenetic processes are critical. The first is the transition
      from an uncommitted pluripotent precursor (mesenchymal stem cell) to the 'transit
      amplifying compartment' of the osteoblast lineage. This transition, normally
      exquisitely regulated in space and time, is abnormal in cancer. The second
      involves termination of lineage expansion, equally tightly regulated under normal
      circumstances. In cancer, the mechanisms that mandate eventual cessation of cell
      division are almost universally disrupted. This model predicts that key
      differentiation genes in bone, such as RUNX2, act in an oncogenic fashion to
      initiate entry into a proliferative phase of cell differentiation, and anti
      oncogenically into the post-mitotic state, resulting in ambivalent roles in
      tumorigenesis. Polycomb genes exemplify epigenetic processes in the stem cell
      compartment and tumorigenesis, and are implicated in skeletal development in
      vivo. The epigenetic functions of the retinoblastoma protein, which plays a key
      role in tumorigenesis in bone, is discussed in the context of terminal cell cycle
      exit.

PMID- 16598745
TI  - Identification of skeletal muscle autoantigens by expression library screening
      using sera from autoimmune rippling muscle disease (ARMD) patients.
AB  - Novel forms of contractile regulation observed in skeletal muscle are evident in
      neuromuscular diseases like rippling muscle disease (RMD). Previous studies of an
      autoimmune form of RMD (ARMD) identified a very high molecular weight skeletal
      muscle protein antigen recognized by ARMD patient antisera. This study utilized
      ARMD and myasthenia gravis (MG) patient antisera, to screen a human skeletal
      muscle cDNA library that subsequently identified proteins that could play a role
      in ARMD. Based on nucleotide sequence analysis, three distinct ARMD antigens were
      identified: titin Isoform N2A, ATP synthase 6, and PPP1R3 (protein phosphatase 1
      regulatory subunit 3). The region of titin identified by ARMD antisera is
      distinct from the main immunogenic region (MIR) recognized by classical MG
      antibodies. Sera from classical MG patient identifies an expressed sequence
      corresponding to the titin MIR. Although the mechanism of antibody penetration is
      not known, previous studies have shown that rippling muscle antibodies affect the
      contractile machinery of myofibers resulting in mechanical sensitivity. Titin's
      role as a modulator of muscle contractility makes it a potential target in
      understanding muscle mechanosensitive regulation.

PMID- 16598746
TI  - Pro-metastasis function of TGFbeta mediated by the Smad pathway.
AB  - The transforming growth factor beta (TGFbeta) signaling pathway plays a vital
      role in the development and homeostasis of normal tissues. Abnormal function of
      this pathway contributes to the initiation and progression of cancer. Smad
      proteins are key signal transducers of the TGFbeta pathway and are essential for
      the growth suppression function of TGFbeta. Smads are bona fide tumor suppressors
      whose mutation, deletion, and silencing are associated with many types of human
      cancer. However, the involvement and functional mechanism of Smad proteins in
      cancer metastasis are poorly defined. Recent studies using genetically modified
      cancer cells and mouse tumor models have provided concrete evidence for a Smad
      dependent mechanism for metastasis promotion by TGFbeta. Understanding the dual
      roles of Smad proteins in tumor initiation and progression has important
      implications for cancer therapeutics.

PMID- 16598747
TI  - Existence of autocrine loop between interleukin-6 and transforming growth factor
      beta1 in activated rat pancreatic stellate cells.
AB  - Interleukin (IL)-6 is a proinflammatory cytokine assumed to participate in
      pancreatic fibrosis by activating pancreatic stellate cells (PSCs). Autocrine TGF
      beta1 is to central in PSC functional regulation. In this study, we examined IL-6
      secretion from culture-activated rat PSCs and its regulatory mechanism. Activated
      PSCs express and secrete IL-6. When anti-TGF-beta1 neutralizing antibody was
      added in the culture medium, IL-6 secretion from activated PSCs was inhibited,
      whereas exogenous TGF-beta1 added in the culture medium enhanced IL-6 expression
      and secretion by PSCs in a dose dependent manner. Infection of PSCs with an
      adenovirus expressing dominant-negative Smad2/3 attenuated basal and TGF-beta1
      stimulated IL-6 expression and secretion of PSCs. We also demonstrated the
      reciprocal effect of PSCs-secreted IL-6 on autocrine TGF-beta1. Anti-IL-6
      neutralizing antibody inhibited TGF-beta1 secretion from PSCs. Preincubation of
      cells with 10 nM PD98059, an extracellular signal-regulated kinase (ERK)
      dependent pathway inhibitor, attenuated IL-6-enhanced TGF-beta1 expression and
      secretion of PSCs. In addition, IL-6 activated ERK in PSCs. These data indicate
      the existence of autocrine loop between IL-6 and TGF-beta1 through ERK- and
      Smad2/3-dependent pathways in activated PSCs.

PMID- 16598748
TI  - Modulation of amino acid uptake by TGF-beta in lung myofibroblasts.
AB  - Hormones such as insulin, growth factors, and cell stress stimulate system A
      amino acid transporter. Transforming growth factor-beta (TGF-beta) stimulates
      amino acid uptake thereby inducing cell proliferation, cellular hypertrophy, and
      matrix synthesis. Insulin appears to activate amino acid in smooth muscle cells
      via a phosphatidylinositol 3-kinase (PI3-kinase)-dependent pathway. We examine
      the effect and interaction of TGF-beta, insulin, and PI3-kinase activity on amino
      acid uptake in human lung myofibroblasts. TGF-beta treatment induced large
      increases in system A activity and a small delayed increase in the
      phosphorylation of protein kinase B, also termed phospho-Akt. In contrast,
      insulin induced small increases in system A activity and large increases in
      phospho-Akt levels. LY294002, a PI3-kinase inhibitor, blocked the TGF-beta
      induced amino acid uptake only partially, but completely blocked TGF-beta-induced
      Akt phosphorylation. Moreover, the level of phospho-Smad3 was found to be high
      even when LY294002 blocked TGF-beta-induced phospho-Akt levels. Inhibition of PI3
      kinase activity resulted in increase in Km, consistent with a major change in
      transporter activity without change in transporter number. The PI3-kinase
      inhibitor also did not change the amino acid transporter 2 (ATA2) mRNA levels.
      Taken together, these results suggest that TGF-beta induced Smad-3 and amino acid
      uptake through a PI3-kinase independent pathway.

PMID- 16598749
TI  - Comparison of anastrozole versus tamoxifen as preoperative therapy in
      postmenopausal women with hormone receptor-positive breast cancer: the Pre
      Operative "Arimidex" Compared to Tamoxifen (PROACT) trial.
AB  - BACKGROUND: The Pre-Operative "Arimidex" Compared to Tamoxifen (PROACT) study was
      a randomized, multicenter study comparing anastrozole with tamoxifen as a
      preoperative treatment of postmenopausal women with large, operable (T2/3, N0-2,
      M0), or potentially operable (T4b, N0-2, M0) breast cancer. The effect of
      preoperative endocrine therapy in patients scheduled for mastectomy or with
      inoperable tumors at baseline was also investigated. METHODS: Patients with
      hormone receptor-positive breast cancer received anastrozole (n = 228) or
      tamoxifen (n = 223) with or without chemotherapy for 12 weeks before primary
      surgery. RESULTS: Objective responses for anastrozole and tamoxifen occurred in
      39.5% and 35.4% of patients, respectively (ultrasound measurements), and 50.0%
      and 46.2% of patients, respectively (caliper measurements). In hormonal therapy
      only patients (n = 314), feasible surgery at baseline improved after 3 months in
      43.0% of patients receiving anastrozole and 30.8% receiving tamoxifen (P = .04).
      In the intent-to-treat population, improvement in feasible surgery at baseline to
      actual surgery at 3 months was found to be numerically higher in the anastrozole
      group compared with the tamoxifen group, although this difference did not reach
      significance. Drug-related adverse events were reported in 20.2% and 18.1% of
      patients, respectively, in the anastrozole and tamoxifen groups. CONCLUSIONS:
      Anastrozole is an effective and well-tolerated preoperative therapy, producing
      clinically beneficial tumor downstaging and reductions in tumor volume. These
      effects enable more minimal surgical interventions in patients scheduled for
      mastectomy, and mastectomy in patients with previously inoperable tumors.
      Anastrozole appears to be at least as effective as tamoxifen in this setting, and
      more effective than tamoxifen in certain clinically relevant subgroups. Cancer
      2006. (c) 2006 American Cancer Society.

PMID- 16598750
TI  - Phase II trial of high-dose, intermittent calcitriol (1,25 dihydroxyvitamin D3)
      and dexamethasone in androgen-independent prostate cancer.
AB  - BACKGROUND: Data suggest that vitamin D plays a role in the treatment and
      prevention of prostate cancer. The combination of high-dose, intermittent
      calcitriol (1,25 dihydroxyvitamin D3) plus dexamethasone was studied based on
      evidence that dexamethasone potentiates the antitumor effects of calcitriol and
      ameliorates hypercalcemia. METHODS: Oral calcitriol was administered weekly,
      Monday, Tuesday, and Wednesday (MTW), at a dose of 8 microg, for 1 month, at a
      dose of 10 microg every MTW for 1 month, and at a dose of 12 microg every MTW
      thereafter. Dexamethasone at a dose of 4 mg was administered each Sunday, and MTW
      weekly. Calcium and creatinine were determined weekly and radiographs of the
      urinary tract were performed every 3 months. All patients were considered
      evaluable for toxicity. RESULTS: Forty-three men with androgen-independent
      prostate cancer were entered; 37 received at least 1 month of calcitriol given at
      a dose of 12 microg every day x 3 per week. The majority of patients had bone
      metastases and rising prostate-specific antigen (PSA) levels. All had an Eastern
      Cooperative Oncology Group performance status of 0 or 1. Eight patients (19%)
      experienced partial responses by PSA criterion (PSA decline of > or =50%,
      persisting for > or = 28 days). Subjective clinical improvement occurred in some
      patients. Toxicity was minimal: urinary tract stones in 2 patients; and a readily
      reversible, CTC (v.3.0) Grade <2 creatinine increase in 4 patients. Throughout
      the study only 4 patients ever had a serum calcium level >11.0 mg/dL and no
      patient had a calcium level >12.0 mg/dL. CONCLUSIONS: The response rate reported
      in the current study (19%) was not found to be clearly higher than expected with
      dexamethasone alone. High-dose intermittent calcitriol plus dexamethasone appears
      to be safe, feasible, and has antitumor activity.

PMID- 16598751
TI  - Phase II study of capecitabine combined with gemcitabine in the treatment of
      androgen-independent prostate cancer previously treated with taxanes.
AB  - BACKGROUND: The primary objective of the current study was to evaluate the
      effectiveness of capecitabine and gemcitabine in the treatment of patients with
      androgen-independent prostate cancer (AIPCa) who experienced disease progression
      after taxane therapy. The secondary objective was to evaluate the safety and
      tolerability of the combination of capecitabine and gemcitabine in these
      patients. METHODS: Patients with AIPCa, either metastatic or unresectable
      disease, and prior taxane therapy were eligible. Patients were treated with 800
      mg/m2 of capecitabine orally twice daily (1600 mg/m2 per day) for 14 days, and
      800 mg/m2 of gemcitabine intravenously on Days 1 and 8. This regimen was repeated
      every 21 days. Response to therapy was determined by measuring prostate-specific
      antigen concentration. RESULTS: Sixteen patients participated in this study from
      June 2003 to January 2004. There were no responses as defined by a 50% decline in
      prostate-specific antigen. The study was terminated early because the response
      rate was not projected to exceed 30% (rejection error of 10%). Toxicities were
      notable: 3 patients had Grade 3 thrombocytopenia, 4 patients had Grade 3
      neutropenia, and 3 patients had Grade 3 infections (according to the National
      Cancer Institute Common Toxicity Criteria [version 2.0]). Eight patients (50%)
      required dose reduction or treatment interruption. CONCLUSIONS: The combination
      of capecitabine and gemcitabine for the salvage treatment of patients with AIPCa
      was associated with significant toxicities and was ineffective for induction of
      disease regression.

PMID- 16598752
TI  - Diabetes modulates differentially creatine kinase-specific activity
      responsiveness to estradiol-17beta and to raloxifene in rat organs.
AB  - Diabetes mellitus increases the risk for CVD in women. While there is
      considerable evidence suggesting beneficial effects of estrogen on decreasing
      lipid peroxidation, atherosclerotic processes, and cardiovascular diseases,
      diabetes negates most estrogen protective effects as well as the skeletal
      protective effects of estrogens, which are not discernable in diabetic women. In
      the present study, we examined the in vivo effects of estradiol-17beta (E2), on
      creatine kinase (CK)-specific activity, in estrogen-responsive organs from
      healthy and diabetic rats. Healthy or diabetic (streptozotocin-induced) female
      rats were injected with either E2 (10-50 microg/rat) or raloxifene (Ral; 500
      1,000 microg/rat). Twenty-four hours following the injection, animals were
      sacrificed; their organs removed and assayed for CK-specific activity. CK
      specific activity in different organs [Left ventricle of heart (Lv), uterus (Ut),
      aorta (Ao), para uterine adipose tissue (Ad), epiphyseal cartilage (Ep), and
      diaphyseal bone (Di)] from healthy animals, was stimulated with increased doses
      of E2, with maximum at 20 microg/rat. Age-matched diabetic female rats exhibited
      a remarkable decreased response to E2 in all organs except Ut. In contrast, the
      response to Ral was not altered in diabetic rats. Similar results were observed
      in organs from ovariectomized female rats (Ovx), healthy or diabetic. These
      results support our previous in vitro findings, demonstrating that hyperglycemia
      decreases CK response to E2 but not to Ral in cultured human vascular and bone
      cells. In summary, diabetes mellitus decreases CK response to E2 but not that of
      Ral in skeletal and vascular tissues. The decreased response to E2 detected in
      organs derived from diabetic rats might be due to changes in nuclear and/or
      membrane estrogen receptors and/or other genomic and non-genomic pathways, as was
      shown in in vitro cellular models.

PMID- 16598753
TI  - Regulation of bone formation by adiponectin through autocrine/paracrine and
      endocrine pathways.
AB  - Since interaction between bone and lipid metabolism has been suggested, this
      study investigated the regulation of bone metabolism by adiponectin, a
      representative adipokine, by analyzing deficient and overexpressing transgenic
      mice. We initially confirmed that adiponectin and its receptors were expressed in
      osteoblastic and osteoclastic cells, indicating that adiponectin can act on bone
      not only through an endocrine pathway as a hormone secreted from fat tissue, but
      also through an autocrine/paracrine pathway. There was no abnormality in bone
      mass or turnover of adiponectin-deficient (Ad-/-) mice, possibly due to an
      equivalent balance of the two pathways. In the culture of bone marrow cells from
      the Ad-/- mice, osteogenesis was decreased compared to the wild-type (WT) cell
      culture, indicating a positive effect of endogenous adiponectin through the
      autocrine/paracrine pathway. To examine the endocrine action of adiponectin, we
      analyzed transgenic mice overexpressing adiponectin in the liver, and found no
      abnormality in the bone. Addition of recombinant adiponectin in cultured
      osteoprogenitor cells suppressed osteogenesis, suggesting that the direct action
      of circulating adiponectin was negative for bone formation. In the presence of
      insulin, however, this suppression was blunted, and adiponectin enhanced the
      insulin-induced phosphorylations of the main downstream molecule insulin receptor
      substrate-1 and Akt. These lines of results suggest three distinct adiponectin
      actions on bone formation: a positive action through the autocrine/paracrine
      pathway by locally produced adiponectin, a negative action through the direct
      pathway by circulating adiponectin, and a positive action through the indirect
      pathway by circulating adiponectin via enhancement of the insulin signaling.

PMID- 16598754
TI  - Circulating levels and clinical significance of soluble CD40 in patients with
      hematologic malignancies.
AB  - BACKGROUND: CD40 plays a critical role in immunoregulation, and CD40 ligation is
      being investigated as a therapy for hematologic malignancies. Although soluble
      CD40 (sCD40) is a potential modulator of both antitumor responses and CD40-based
      therapies, the levels and significance of sCD40 in patients with hematologic
      malignancies are unknown. METHODS: The authors evaluated serum/plasma sCD40
      levels using an enzyme-linked immunoassay in patients with acute myeloid leukemia
      (AML), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), mantle
      cell lymphoma (MCL), and multiple myeloma (MM). RESULTS: Levels of sCD40 were
      elevated in serum (>1.697 ng/mL) or plasma (>0.649 ng/mL) from 73% of patients
      with CLL, 80% of patients with MCL, 40% of patients with AML, 43% of patients
      with MDS, and 33% of patients with MM. Multivariate analysis of patients with MM
      demonstrated that elevated sCD40 was a significant, independent predictor of poor
      survival. In multivariate analysis of patients with AML, sCD40 was a significant
      prognostic factor when the interaction of age and sCD40 was included as a
      variable. Further analysis demonstrated that elevated sCD86 levels were
      associated with significantly shorter survival only in AML patients younger than
      age 64 years. Release of sCD40 by CLL cells was induced by cross-linking with
      CD40 monoclonal antibody. CONCLUSIONS: Many patients with hematologic
      malignancies have elevated circulating levels of sCD40, and these elevated levels
      are associated with a poor prognosis at least in patients with MM and AML,
      suggesting that sCD40 may have a role in modulating antitumor responses and also
      may be a useful prognostic marker. In addition, the findings suggested that
      further studies will be required to determine the effect of circulating sCD40 on
      the clinical effectiveness of CD40-ligating reagents used in the treatment of
      hematologic malignancies.

PMID- 16598755
TI  - CREB-dependent cyclooxygenase-2 and microsomal prostaglandin E synthase-1
      expression is mediated by protein kinase C and calcium.
AB  - Cellular production of prostaglandins (PGs) is controlled by the concerted
      actions of cyclooxygenases (COX) and terminal PG synthases on arachidonic acid in
      response to agonist stimulation. Recently, we showed in an ileal epithelial cell
      line (IEC-18), angiotensin II-induced COX-2-dependent PGI2 production through
      p38MAPK, and calcium mobilization (J. Biol. Chem. 280: 1582-1593, 2005). Agonist
      binding to the AT1 receptor results in activation of PKC activity and Ca2+
      signaling but it is unclear how each pathway contributes to PG production. IEC-18
      cells were stimulated with either phorbol-12,13-dibutyrate (PDB), thapsigargin
      (TG), or in combination. The PG production and COX-2 and PG synthase expression
      were measured. Surprisingly, PDB and TG produced PGE2 but not PGI2. This
      corresponded to induction of COX-2 and mPGES-1 mRNA and protein. PGIS mRNA and
      protein levels did not change. Activation of PKC by PDB resulted in the
      activation of ERK1/2, JNK, and CREB whereas activation of Ca2+ signaling by TG
      resulted in the delayed activation of ERK1/2. The combined effect of PKC and Ca2+
      signaling were prolonged COX-2 and mPGES-1 mRNA and protein expression.
      Inhibition of PKC activity, MEK activity, or Ca2+ signaling blocked agonist
      induction of COX-2 and mPGES-1. Expression of a dominant negative CREB (S133A)
      blocked PDB/TG-dependent induction of both COX-2 and mPGES-1 promoters. Decreased
      CREB expression by siRNA blocked PDB/TG-dependent expression of COX-2 and mPGES-1
      mRNA. These findings demonstrate a coordinated induction of COX-2 and mPGES-1 by
      PDB/TG that proceeds through PKC/ERK and Ca2+ signaling cascades, resulting in
      increased PGE2 production.

PMID- 16598756
TI  - Maintenance therapy with thalidomide improves overall survival after autologous
      hematopoietic progenitor cell transplantation for multiple myeloma.
AB  - BACKGROUND: High-dose chemotherapy with autologous hematopoietic progenitor cell
      (HPC) transplantation improves survival for patients with multiple myeloma (MM);
      however, most patients develop recurrent disease after undergoing
      transplantation, and new treatment approaches are needed. The objective of this
      retrospective review of autologous HPC transplantation for patients with MM was
      to evaluate the impact of conditioning regimens and posttransplantation therapy
      on survival. METHODS: The authors reviewed 112 patients with MM who received
      autologous HPC grafts at their institution. Between June 1992 and August 2001, 54
      patients received busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16), and 58
      patients received high-dose melphalan (MEL-200) followed by autologous HPC
      transplantation. After transplantation, 36 patients received thalidomide for
      maintenance or salvage therapy, and 76 patients received no posttransplantation
      thalidomide. RESULTS: At a median follow-up of 58 months, the median survival was
      54 months. There was no statistically significant difference noted with regard to
      response to conditioning regimen, progression-free survival, or overall survival
      between the Bu/Cy/VP-16 and MEL-200 cohorts. Patients who received thalidomide
      after transplantation had improved median survival (65.5 months) compared with
      patients who did not receive thalidomide (44.5 months; P = .09). When they were
      separated according to reasons for thalidomide use, patients who received
      thalidomide as maintenance had improved overall survival compared with patients
      who received thalidomide as salvage (65 months vs. 54 months; P = .05).
      CONCLUSIONS: Combination chemotherapy provided no advantage over high-dose
      melphalan in patients with MM who underwent autologous HPC transplantation. The
      posttransplantation use of thalidomide seemed to improve the survival of patients
      compared with historical controls from the prethalidomide era. Further
      prospective trials are underway to confirm the benefit of thalidomide in the
      posttransplantation setting.

PMID- 16598757
TI  - The methylation status and protein expression of CDH1, p16(INK4A), and fragile
      histidine triad in nonsmall cell lung carcinoma: epigenetic silencing, clinical
      features, and prognostic significance.
AB  - BACKGROUND: Aberrant methylation of the promoter CpG island (methylation) is
      known as a major inactivation mechanism of tumor suppressor and tumor-related
      genes. In this study, the authors studied the presence of methylation by
      investigated the inactivation of genes and prognostic factors in patients with
      nonsmall cell lung carcinoma (NSCLC) by examining resection samples for the
      presence of methylation. METHODS: Samples were obtained from 224 patients who
      underwent pulmonary resection for NSCLC. The authors used those samples to study
      methylation status with methylation-specific polymerase chain reaction analysis
      and to study protein expression with immunohistochemistry for 3 different genes:
      CDH1, p16INK4A, and fragile histidine triad (FHIT). RESULTS: The frequency of
      methylation in NSCLC was determined as 58.0% for CDH1, 21.9% for p16INK4A, and
      52.2% for FHIT. The methylation of p16INK4A was observed significantly in heavy
      smokers compared either with nonsmokers or with patients who had smoked for <20
      pack-years (P = .0420); it also was more significant in squamous cell carcinomas
      than in adenocarcinomas (P = .0343). FHIT methylation also was correlated
      significantly with lymph node metastasis (P = .0361). Patients who had tumors
      with both methylation and reduced expression of CDH1 had a significantly poorer
      prognosis compared with patients who had tumors both without methylation and with
      positive expression of CDH1 (P = .0259 and P = .0369, respectively; multivariate
      Cox analysis). For p16INK4A methylation, 63.3% of tumors showed reduced
      expression; whereas, in p16INK4A-unmethylated tumors, 33.7% showed reduced
      expression (P = .0002). However, for CDH1 and FHIT, no significant correlation
      was found for either methylation or reduced expression. CONCLUSIONS: Although
      protein expression was not inactivated by methylation alone, p16 expression was
      inactivated strongly by methylation. In addition, the analysis of methylation and
      expression of CDH1 played a clinically important role in treatment strategies for
      patients with NSCLC.

PMID- 16598759
TI  - Alteration in cellular functions in mouse macrophages after exposure to 50 Hz
      magnetic fields.
AB  - The aim of the present study is to investigate whether extremely low frequency
      electromagnetic fields (ELF-EMF) affect certain cellular functions and
      immunologic parameters of mouse macrophages. In this study, the influence of 50
      Hz magnetic fields (MF) at 1.0 mT was investigated on the phagocytic activity and
      on the interleukin-1beta (IL-1beta) production in differentiated macrophages. MF
      exposure led to an increased phagocytic activity after 45 min, shown as a 1.6
      fold increased uptake of latex beads in MF-exposed cells compared to controls. We
      also demonstrate an increased IL-1beta release in macrophages after 24 h exposure
      (1.0 mT MF). Time-dependent IL-1beta formation was significantly increased
      already after 4 h and reached a maximum of 12.3-fold increase after 24 h compared
      to controls. Another aspect of this study was to examine the genotoxic capacity
      of 1.0 mT MF by analyzing the micronucleus (MN) formation in long-term (12, 24,
      and 48 h) exposed macrophages. Our data show no significant differences in MN
      formation or irregular mitotic activities in exposed cells. Furthermore, the
      effects of different flux densities (ranging from 0.05 up to 1.0 mT for 45 min)
      of 50 Hz MF was tested on free radical formation as an endpoint of cell
      activation in mouse macrophage precursor cells. All tested flux densities
      significantly stimulated the formation of free radicals. Here, we demonstrate the
      capacity of ELF-EMF to stimulate physiological cell functions in mouse
      macrophages shown by the significantly elevated phagocytic activity, free radical
      release, and IL-1beta production suggesting the cell activation capacity of ELF
      EMF in the absence of any genotoxic effects.

PMID- 16598758
TI  - Methotrexate induced differentiation in colon cancer cells is primarily due to
      purine deprivation.
AB  - The folate antagonist methotrexate (MTX) inhibits synthesis of tetrahydrofolate
      (THF), pyrimidines and purines, and induces differentiation in several cell
      types. At 1 microM, MTX reduced proliferation and induced differentiation in HT29
      colon cancer cells; the latter effect was augmented (P < 0.001) by thymidine (100
      microM) but was reversed (P < 0.001) by the purines, hypoxanthine (Hx; 100
      microM) and adenosine (100 microM). In contrast 5-fluoro-uracil (5-FU), a
      specific thymidylate synthase (TS) inhibitor, had no effect on differentiation,
      suggesting that MTX-induced differentiation is not due to a reduction in
      thymidine but to the inhibition of purine biosynthesis. Inhibition of cyclic AMP
      (cAMP) by RpcAMP (25 microM) further enhanced (P < 0.001) MTX induced
      differentiation, whereas the cAMP activator forskolin (10 microM) reversed (P <
      0.001) MTX induced differentiation. These observations implicate a central role
      of adenosine and cAMP in MTX induced differentiation. By combining Western blot
      analysis with liquid chromatography-mass spectrometry (LC-MS)and HPLC analyses we
      also reveal both the expression and activity of key enzymes (i.e. methionine
      synthase (MS), s-adenosylhomocysteinase, cystathionine beta-synthase and
      ornithine decarboxylase) regulating methyl cycle, transsulfuration and polyamine
      pathways in HT29 colon cancer cells. At 1 microM, MTX induced differentiation was
      associated with a marked reduction in the intracellular concentrations of
      adenosine and, consequently, S-adenosylmethionine (SAM), S-adenosylhomocysteine,
      polyamines and glutathione (GSH). Importantly, the marked reduction in methionine
      that accompanied MS inhibition following MTX treatment was non-limiting with
      respect to SAM synthesis. Collectively, these findings indicate that the effects
      of MTX on cellular differentiation and single carbon metabolism are primarily due
      to the intracellular depletion of purines.

PMID- 16598760
TI  - Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and
      synchronous methylation of nonsmall cell lung cancer.
AB  - BACKGROUND: Both genetic and epigenetic changes in nonsmall cell lung cancer
      (NSCLC) are known to be a common event. METHODS: Mutations in the epidermal
      growth factor receptor gene (EGFR), HER-2, and KRAS and the methylation profile
      of 9 genes for NSCLC were analyzed and correlated with clinical and histologic
      data. RESULTS: Thirty-nine EGFR, 4 HER-2, and 6 KRAS mutations were found in 150
      NSCLC cases, with the methylation percentages of the genes ranging from 13% to
      54%. Most mutations were present in adenocarcinomas, but mutations of the 3 genes
      were never found to be present in individual tumors. The frequency of methylation
      for all the genes was correlated with the Methylation Index, a reflection of the
      overall methylation pattern (all genes, P< or = .01), supporting the presence of
      the CpG island methylator phenotype (CIMP) in NSCLC. On the basis of the
      methylation profile, CRBP1 and CDH13 methylation were good indicators of CIMP in
      NSCLC, and were correlated with a poorer prognosis in adenocarcinomas. Mutations
      in EGFR, HER-2, and KRAS were found to be present exclusively, whereas
      methylation tended to be present synchronously. A comparison of mutation and
      methylation demonstrated that the EGFR mutation had an inverse correlation with
      methylation of SPARC (secreted protein acidic and rich in cysteine), an
      extracellular Ca2+-binding matricellular glycoprotein associated with the
      regulation of cell adhesion and growth, and the p16INK4A gene. CONCLUSIONS: The
      findings of the current study suggest that adenocarcinoma cases with CIMP have a
      poorer prognosis than adenocarcinoma cases without CIMP, and the EGFR mutation
      was shown to have an inverse correlation with methylation of SPARC and the
      p16INK4A gene in NSCLC.

PMID- 16598762
TI  - Phase II trial of combined irinotecan and oxaliplatin given every 3 weeks to
      patients with metastatic colorectal cancer.
AB  - BACKGROUND: Both irinotecan and oxaliplatin are active agents in the treatment of
      patients with metastatic colorectal cancer, and there is a strong preclinical
      rationale for combining these 2 agents. Therefore, a Phase II trial was designed
      and conducted to determine the efficacy and tolerability of combined irinotecan
      and oxaliplatin given every 3 weeks to patients with metastatic colorectal
      cancer. METHODS: Patients with previously untreated metastatic colorectal cancer
      received irinotecan at a dose of 175 mg/m2 and oxaliplatin at a dose of 130
      mg/m2, both given intravenously every 3 weeks. Objective responses were evaluated
      every 2 courses and were confirmed at least 4 weeks after the initial
      determination. RESULTS: Fifty-five patients were enrolled and treated in the
      current trial. Of the 53 patients whose responses were evaluable, 18 (34%)
      achieved a partial response, 27 (51%) had stable disease, and 8 (15%) developed
      disease progression as their best response to the treatment. The intent-to-treat
      median survival for all patients was 16.4 months and the time to progression was
      4.8 months. All 55 patients were available for toxicity analysis (according to
      version 2.0 of the National Cancer Institute Common Toxicity Criteria). The most
      common Grade 3-4 toxic effect was neutropenia, which was reported to occur in 22
      patients (40%). CONCLUSIONS: The combination of irinotecan and oxaliplatin
      appears to be safe and active when used to treat patients with metastatic
      colorectal cancer. Treatment results with this regimen were similar to those
      reported for other combined frontline chemotherapy regimens for colorectal
      cancer. When this particular regimen wa used, neutropenia was found to be the
      predominant toxicity.

PMID- 16598761
TI  - Pre-radiation chemotherapy with response-based radiation therapy in children with
      central nervous system germ cell tumors: a report from the Children's Oncology
      Group.
AB  - BACKGROUND: This Phase II study was designed to determine response to
      chemotherapy and survival after response-based radiation (RT) in children with
      CNS germ cell tumors. PROCEDURE: Children with germinomas and normal markers
      received cisplatin 100 mg/m(2) + etoposide, alternating with vincristine +
      cyclophosphamide (CPM) 2 g/m(2)/d, for four cycles. Children with
      nongerminomatous tumors or with abnormal markers received doubled doses of
      cisplatin and CPM. For germinoma patients in complete response (CR), RT was
      decreased from 50.4 to 30.6 Gy. High-risk patients received neuraxis RT: 50.4 Gy
      local + 30.6 Gy neuraxis in CR; 54 Gy local + 36 Gy if less than CR. RESULTS: Of
      12 germinoma patients, 4 had cerebrospinal fluid (CSF) human chorionic
      gonadotropin (HCG) 6.9-21 mIU/ml. Of 14 nongerminomatous patients, HCG in serum
      or CSF was >50 mIU/ml in 9, alpha-fetoprotein (AFP) abnormal in 9. Four germinoma
      patients attained CR, six PR, one SD, one not evaluable after resection. Two
      nongerminomatous patients had CR, three PR, three SD, one PD, four not evaluable
      after resection; one inadequately treated patient had progressive disease (PD).
      Both PD patients died; one SD patient died during a seizure. Eleven germinoma
      patients are PF at median 66 months; one patient in CR refused RT, had PD at 10
      months, received RT, and was PF at 56 months. Eleven of 14 nongerminomatous
      patients were PF at median 58 months. CONCLUSION: Response (germinoma, 91%;
      nongerminomatous, 55%) and survival are encouraging after this regimen plus
      response-based RT.

PMID- 16598763
TI  - UVB-induced 1,25(OH)2D3 production and vitamin D activity in intestinal CaCo-2
      cells and in THP-1 macrophages pretreated with a sterol Delta7-reductase
      inhibitor.
AB  - Epidermal keratinocytes are able to produce 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] and induce vitamin D activity upon UVB irradiation. To find out
      whether this property is keratinocyte specific, we investigated this
      characteristic in two other cell types, namely intestinal CaCo-2 cells and the
      macrophage-like differentiated THP-1 cells. THP-1 macrophages and preconfluent
      CaCo-2 cells contain the vitamin D receptor (VDR), possess 25-hydroxylase (CYP2R1
      and CYP27A1) and 1alpha-hydroxylase (CYP27B1) activity, and survive the low UVB
      doses essential for vitamin D3 photoproduction. Upon irradiation, 24-hydroxylase
      (CYP24) mRNA is induced in both cell types pretreated with the sterol Delta7
      reductase inhibitor BM15766 whereby the 7-dehydrocholesterol (7-DHC) content was
      increased. Transfection studies in CaCo-2 cells with a vitamin D response element
      containing construct revealed the involvement of the VDR in this UVB-dependent
      CYP24 induction. The CYP24 inducing activity in BM15766-pretreated UVB-irradiated
      CaCo-2 cells and THP-1 macrophages was identified as 1,25(OH)2D3 by combined high
      performance liquid chromatography radioimmunoassay. Addition of vitamin D binding
      protein to the CaCo-2 cells attenuated UVB-induced CYP24 induction suggesting the
      possibility of a paracrine or autocrine role for the photoproduced 1,25(OH)2D3.
      In conclusion, preconfluent CaCo-2 cells and THP-1 macrophages are able to induce
      vitamin D activity upon UVB irradiation and hence combine all parts of the
      vitamin D photoendocrine system, a characteristic which is therefore not
      keratinocyte specific.

PMID- 16598764
TI  - RUNX3: a new player in myeloid gene expression and immune response.
AB  - RUNX transcription factors function as scaffolds for interaction with various
      coregulatory proteins during developmental processes such as hematopoiesis,
      neurogenesis, and osteogenesis. The current view places RUNX proteins within the
      TGF-beta signaling pathway, although each one exhibits cell- and tissue-specific
      functions. In the case of RUNX3, recent data have suggested its function as a
      tumor suppressor factor and highlighted its involvement in immune cell
      differentiation and activation. The molecular mechanisms for the pleiotropic
      effects of Runx3 deficiency are not completely understood. The present article
      will summarize the known functional activities of RUNX3, emphasizing its role in
      myeloid cell gene expression and its potential contribution to the migratory and
      adhesive capabilities of this cell lineage.

PMID- 16598765
TI  - Nuclear addressing provides a clue for the transforming activity of amino
      truncated CCN3 proteins.
AB  - CCN3 is a founding member of the CCN (Cyr61, Ctgf, Nov) family of cell growth and
      differentiation regulators. These secreted proteins are key regulators in
      embryonic development, and are associated with severe pathologies including
      fibrotic diseases and cancers. CCN3 was discovered as a MAV integration site in
      an avian nephroblastoma. Previous work established that the amino-truncated
      protein expressed in this tumor was inducing morphological transformation of
      chicken embryo fibroblasts, whereas the full-length secreted CCN3 protein was
      inhibiting cell growth. Amino-truncated variants were identified in cancer cell
      lines. Since the lack of signal peptide was expected to alter the fate of the
      truncated proteins, we hypothesized that modifications of CCN3 subcellular
      addressing could be responsible for the oncogenic activities of CCN3. The CCN
      proteins are composed of four structural modules (IGFBP, TSP1, VWC, and CT). We
      report that amino-truncated variants of CCN3 are addressed to the nucleus and
      that the carboxyterminal (CT) module of CCN3 is responsible for the nuclear
      addressing. Furthermore, our data identify nuclear CCN3 variants as potential
      transcriptional regulators. In this context, the CT module confers on nuclear
      CCN3 proteins a negative regulatory effect on transcription. We propose that the
      nuclear localization of amino-truncated CCN3 proteins be correlated to
      oncogenicity.

PMID- 16598766
TI  - p27kip1 overexpression promotes paclitaxel-induced apoptosis in pRb-defective
      SaOs-2 cells.
AB  - p27kip1 is a cyclin-dependent kinase (CDK) inhibitor, which controls several
      cellular processes in strict collaboration with pRb. We evaluated the role of
      p27kip1 in paclitaxel-induced apoptosis in the pRb-defective SaOs-2 cells.
      Following 48 h of exposure of SaOs-2 cells to 100 nM paclitaxel, we observed an
      increase in p27kip1 expression caused by the decrease of the ubiquitin-proteasome
      activity. Such increase was not observed in SaOs-2 cells treated with the caspase
      inhibitors Z-VAD-FMK, suggesting that p27kip1 enhancement at 48 h is strictly
      related to apoptosis. Finally, we demonstrated that SaOs-2 cells transiently
      overexpressing the p27kip1 protein are more susceptible to paclitaxel-induced
      apoptosis than SaOs-2 cells transiently transfected with the empty vector.
      Indeed, after 48 h of paclitaxel treatment, 41.8% of SaOs-2 cells transiently
      transfected with a pcDNA3-p27kip1 construct were Annexin V-positive compared to
      30.6% of SaOs-2 cells transfected with the empty vector (P < 0.05). In
      conclusion, we demonstrated that transfection of the pRb-defective SaOs-2 cells
      with the p27kip1 gene via plasmid increases their susceptibility to paclitaxel
      induced apoptosis. The promoting effect of p27kip1 overexpression on apoptosis
      makes p27kip1 and proteasomal inhibitors interesting tools for therapy in
      patients with pRb-defective cancers.

PMID- 16598767
TI  - Stable formation of mutated p53 multimers in a Chinese hamster cell line causes
      defective p53 nuclear localization and abrogates its residual function.
AB  - We have previously described a methotrexate-resistant cell line (MTX M)
      characterized by amplified dihydrofolate reductase (DHFR) genes, cytoplasmic p53
      localization, and p53 stable tetramers. To investigate the p53 functionality in
      MTX M, the effect of chemical/physical agents was studied. In MTX M cells, DNA
      damage did not induce p53 or mdm-2 protein, while in the parental V79 cells, a
      residual p53 activity was found. cDNA sequencing showed that V79 and MTX M cells
      share the same mutations, indicating that the complete loss of p53 function in
      MTX M cells was due to cytoplasmic sequestration of a mutated p53 with residual
      activity. In Chinese hamster, both p53 and DHFR genes map on short arm of
      chromosome 2 suggesting that p53 itself might be amplified. However, fluorescence
      in situ hybridization with a hamster p53 probe showed only a single signal. Thus,
      the presence of p53 stable tetramers in MTX M cells, although correlated with DNA
      amplification, could not be the consequence of either p53 or DHFR gene
      amplification. Expression of a C-terminal human p53 peptide does not induce p53
      nuclear accumulation, indicating that the cytoplasmic localization is due to a
      mechanism different from that already described in cancer cell lines. Treatments
      with Sodium Butyrate induced beta-tubulin polymerization, but did not apparently
      organize a normal microtubule network, which is shown to be important for the p53
      localization. Our data indicated that in MTX M cells, p53 is sequestered in the
      cytoplasm by a novel mechanism that abrogates p53 residual function.

PMID- 16598768
TI  - CK2 signaling in androgen-dependent and -independent prostate cancer.
AB  - Protein serine/threonine kinase casein kinase 2 (CK2) is a key player in cell
      growth and proliferation but is also a potent suppressor of apoptosis. CK2 has
      been found to be dysregulated in all the cancers that have been examined,
      including prostate cancer. Investigations of CK2 signaling in the prostate were
      originally initiated in this laboratory, and these studies have identified
      significant functional activities of CK2 in relation to normal prostate growth
      and to the pathobiology of androgen-dependent and -independent prostate cancer.
      We present a brief overview of these developments in the context of prostate
      biology. An important outcome of these studies is the emerging concept that CK2
      can be effectively targeted for cancer therapy.

PMID- 16598769
TI  - Androgen axis in prostate cancer.
AB  - Endocrine therapy for advanced prostate cancer is based on androgen ablation or
      blockade of the androgen receptor (AR). AR action in prostate cancer has been
      investigated in a number of cell lines, their derivatives, and transgenic
      animals. AR expression is heterogenous in prostate cancer in vivo; it could be
      detected in most primary tumors and their metastases. However, some cells lack
      the AR because of epigenetic changes in the gene promoter. AR expression
      increases after chronic androgen ablation in vitro. In several xenografts, AR
      upregulation is the most consistent change identified during progression towards
      therapy resistance. In contrast, the AR pathway may be by-passed during chronic
      treatment with a nonsteroidal anti-androgen. AR sensitivity in prostate cancer
      increases as a result of activation of the Ras/mitogen-activated protein kinase
      pathway. One of the major difficulties in endocrine therapy for prostate cancer
      is acquisition of agonistic properties of AR antagonists observed in the presence
      of mutated AR. Enhancement of AR function by associated coactivator proteins has
      been extensively investigated. Cofactors SRC-1, RAC3, p300/CBP, TIF-2, and Tip60
      are upregulated in advanced prostate cancer. Most studies on ligand-independent
      activation of the AR are focused on Her-2/neu and interleukin-6 (IL-6). On the
      basis of studies that showed overexpression and activation of the AR in advanced
      prostate cancer, it was suggested that novel therapies that reduce AR expression
      will provide a benefit to patients. There is experimental evidence showing that
      prostate tumor growth in vitro and in vivo is inhibited following administration
      of chemopreventive drugs or antisense oligonucleotides that downregulate AR mRNA
      and protein expression.

PMID- 16598770
TI  - In vitro toxicology evaluation of pharmaceuticals using Raman micro-spectroscopy.
AB  - Raman micro-spectroscopy combined with multivariate analysis was employed to
      monitor real-time biochemical changes induced in living cells in vitro following
      exposure to a pharmaceutical. The cancer drug etoposide (topoisomerase II
      inhibitor) was used to induce double-strand DNA breaks in human type II
      pneumocyte-like cells (A549 cell-line). Raman spectra of A549 cells exposed to
      100 microM etoposide were collected and classical least squares (CLS) analysis
      used to determine the relative concentrations of the main cellular components. It
      was found that the concentrations of DNA and RNA significantly (P < 0.05)
      decreased, whilst the concentration of lipids significantly (P < 0.05) increased
      with increasing etoposide exposure time as compared to control untreated A549
      cells. The concentration of DNA decreased by 27.5 and 87.0% after 24 and 48 h
      exposure to etoposide respectively. Principal components analysis (PCA)
      successfully discriminated between treated and untreated cells, with the main
      variance between treatment groups attributed to changes in DNA and lipid. DNA
      fragmentation was confirmed by Western blot analysis of apoptosis regulator
      protein p53 and cell metabolic activity determined by MTT assay. The over
      expression of p53 protein in the etoposide treated cells indicated a significant
      level of DNA fragmentation and apoptosis. MTT tests confirmed that cellular
      metabolic activity decreased following exposure to etoposide by 29.4 and 61.2%
      after 24 and 48 h, respectively. Raman micro-spectroscopy may find applications
      in the toxicology screening of other drugs, chemicals and new biomaterials, with
      a range of cell types.

PMID- 16598771
TI  - Chaperone-like activity revealed in the matricellular protein SPARC.
AB  - SPARC (Secreted Protein, Acidic and Rich in Cysteine) is a matricellular
      glycoprotein that modulates cell proliferation, adhesion, migration, and
      extracellular matrix (ECM) production. In this report chaperone-like activity of
      SPARC was identified in a thermal aggregation assay in vitro. Ultraviolet
      circular dichroism (UVCD) spectroscopy determined that SPARC was stable at
      temperatures up to 50 degrees C. Unfolding and aggregation of the chaperone
      target protein, alcohol dehydrogenase (ADH), were initiated at 50 degrees C.
      SPARC inhibited the thermal aggregation of ADH in a concentration-dependent
      manner, with maximal inhibition at a 1:4 molar ratio of SPARC:ADH. Synergy
      between the chaperone-like activities of SPARC and alphaB-crystallin, a small
      heat shock protein and molecular chaperone in the lens, was observed in SPARC
      alphaB-crystallin double -/- mice.

PMID- 16598772
TI  - Membrane proteinase 3 and its interactions within microdomains of neutrophil
      membranes.
AB  - Proteinase 3 (PR3) is a serine protease of neutrophil granules released to the
      medium or into the phagocytic vesicle upon neutrophil stimulation. A fraction of
      the enzyme is thought to associate with the cell membrane yielding membrane PR3
      (mPR3). In autoimmune disorders characterized by the presence of antineutrophil
      cytoplasmic antibodies (ANCA), the reaction of the latter with their target
      antigen mPR3 activates the cell inflicting injuries on the surrounding tissues.
      In a previous communication we provided evidence for the presence of mPR3 in
      lipid rafts obtained by lysis of neutrophils in Triton X-100 and for the
      mediation of PR3 binding to the membrane by a glycosylphosphatidylinositol (GPI)
      anchored neutrophil protein, possibly FcgammaRIIIb. In the current study we
      employed the mild detergent Brij 58 to isolate high molecular weight (HMW)
      protein complexes in the void volume of a Sepharose 4B gel filtration minicolumn.
      HMW complexes of unstimulated neutrophils comprised PR3, FcgammaRIIIb, the beta2
      integrin CD11b/CD18 as well as the membrane and cytosolic subunits of the NADPH
      oxidase, p22phox and p47phox/p67phox. Treatment of neutrophils with
      phosphatidylinositol-specific phospholipase C (PI-PLC) reduced amounts of PR3 and
      FcgammaRIIIb in HMW complexes isolated from the treated cells, supporting our
      previous suggestion that FcgammaRIIIb acts as a membrane adaptor for PR3.
      FcgammaRIIIb of HMW fractions co-immunoprecipitated with PR3, indicating their
      presence in the same protein complex. Since HMW fractions contained also the
      majority of biotinylated proteins obtained by the reaction of neutrophils with a
      membrane impermeable biotinylating agent Sulfo-NHS-biotin, it was concluded that
      HMW proteins were derived from cell membranes. Lipid rafts isolated from Brij 58
      lysed neutrophils were similar in their protein composition to the HMW complexes
      but not identical.

PMID- 16598773
TI  - 17beta-estradiol (E2) induces cdc25A gene expression in breast cancer cells by
      genomic and non-genomic pathways.
AB  - Cdc25A is a potent tyrosine phosphatase that catalyzes specific dephosphorylation
      of cyclin/cyclin-dependent kinase (cdk) complexes to regulate G1 to S-phase cell
      cycle progression. Cdc25A mRNA levels are induced by 17beta-estradiol (E2) in ZR
      75 breast cancer cells, and deletion analysis of the cdc25A promoter identified
      the -151 to -12 region as the minimal E2-responsive sequence. Subsequent
      mutation/deletion analysis showed that at least three different cis-elements were
      involved in activation of cdc25A by E2, namely, GC-rich Sp1 binding sites, CCAAT
      motifs that bind NF-Y, and E2F sites that bind DP/E2F1 proteins. Studies with
      inhibitors and dominant negative expression plasmids show that E2 activates
      cdc25A expression through activation of genomic ERalpha/Sp1 and E2F1 and cAMP
      dependent activation of NF-YA. Thus, both genomic and non-genomic pathways of
      estrogen action are involved in induction of cdc25A in breast cancer cells.

PMID- 16598774
TI  - Elevated serum kininogen in patients with Paget's disease of bone: a role in
      marrow stromal/preosteoblast cell proliferation.
AB  - Paget's disease (PD) of bone is a chronic focal skeletal disorder characterized
      by excessive bone resorption followed by abundant new bone formation. Enhanced
      levels of IL-6, RANKL, M-CSF, and endothelin-1 have been associated with PD. In
      the present study, we identified increased serum levels (2 to 5-fold) of
      inflammatory cytokine, kininogen (KNG) in patients with PD compared to normal
      subjects. Treatment of pagetic bone marrow derived stromal/preosteoblast cells
      with recombinant KNG (25 ng/ml) for 24 h period resulted in a 5-fold increase in
      the levels of phospho-HSP27 and a 3-fold increase in ERK1/2 phosphorylation in
      these cells. However, pagetic stromal cells stimulated with KNG in the presence
      of ERK activation inhibitor peptide did not significantly affect the levels of
      phospho-HSP27. KNG increased normal and pagetic marrow stromal cell proliferation
      at 1.4-fold and 2.5-fold, respectively. KNG in the presence of an ERK inhibitor
      peptide did not stimulate pagetic marrow stromal cell proliferation. Furthermore,
      siRNA suppression of HSP27 expression significantly decreased KNG inhibition of
      etoposide-induced caspase-3 activation and apoptosis in these cells. In summary,
      KNG modulate bone marrow derived stromal/preosteoblast cell proliferation and
      suppress etoposide-induced apoptosis through ERK and HSP27 activation,
      respectively. These results implicate a pathophysiologic role for KNG in patients
      with PD.

PMID- 16598775
TI  - Differential expression of proteins in kidney, eye, aorta, and serum of diabetic
      and non-diabetic rats.
AB  - Diabetes mellitus (DM) is a chronic progressive disease that often results in
      microvascular and macrovascular complications, yet its pathogenesis is not clear.
      Automated proteomic technology, coupled with powerful bioinformatics and
      statistical tools, can provide new insights into the molecular alterations
      implicated in DM. Following our previous findings of redox changes in the eye and
      aorta of diabetic rats, as well as the activities of different antioxidant
      enzymes during the development of DM, this study is further launched to find
      potential biomarkers by comparing the serum and tissue samples of 26 diabetic
      rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls
      using surface enhanced laser desorption/ionization time-of-flight mass
      spectrometry (SELDI-TOF MS) technology. Eight potential biomarkers were found in
      the serum, one potential biomarker was found in the kidney and eye, respectively,
      whereas three potential biomarkers were discovered in the aorta. One of the serum
      biomarker candidates was found to match the C-reactive protein (CRP) in the Swiss
      Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm
      the role of CRP during the development of DM. To conclude, the increased level of
      CRP in diabetic serum demonstrated in this study indicates that the development
      of DM is associated with inflammation. This is also the first report
      demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta
      may be involved in the development of diabetes and its complications. Further
      identification and evaluation of these potential biomarkers will help unravel the
      underlying mechanisms of the disease.

PMID- 16598776
TI  - Hypoxia and DNA-damaging agent bleomycin both increase the cellular level of the
      protein 4E-BP.
AB  - The 4E-binding proteins (4E-BPs) regulate the cap-dependent eukaryotic initiation
      factor 4E (eIF4E). The level of 4E-BP protein is regulated during early
      development of sea urchin embryos. Fertilization leads to the rapid disappearance
      of the protein that reappears later in development. We show that two important
      cellular stresses, hypoxia and bleomycin prolonged checkpoint mobilization
      provoked the overexpression of the protein 4E-BP in developing sea urchin
      embryos. Hypoxia resulted after 1 h in a reversible gradual increase in the
      protein 4E-BP level. At 20 h, the protein 4E-BP had reached the level existing in
      the unfertilized eggs. Bleomycin used as a DNA-damaging agent for checkpoint
      activation, provoked cell cycle inhibition and after prolonged exposure (20 h),
      induced the expression of the protein 4E-BP. The effect of bleomycin on 4E-BP
      protein overexpression was dose-dependent between 0.4 and 1.2 mM. The role of the
      overexpression of the protein 4E-BP is discussed in relation with cellular stress
      responses.

PMID- 16598777
TI  - Safety, tolerability, and efficacy of everolimus in de novo liver transplant
      recipients: 12- and 36-month results.
AB  - Everolimus is a macrolide immunosuppressive agent with known consistent
      absorption. In this double-blind study, we examined the safety and tolerability
      of everolimus vs. placebo in de novo liver transplant recipients. One hundred and
      nineteen liver allograft recipients were randomized to 1 of 4 groups: everolimus
      0.5 mg bid, everolimus 1.0 mg bid, everolimus 2 mg bid, or placebo. Patients
      received oral cyclosporine to achieve a target trough level of 150-400 ng/mL in
      combination with prednisone. Primary and secondary endpoints of safety,
      tolerability, and efficacy were determined at 12 months, and patients were
      followed through 36 months. There was a trend toward fewer treated acute
      rejections in the everolimus group than in the placebo group: everolimus 0.5 mg:
      39.3%; everolimus 1.0 mg: 30.0%; everolimus 2 mg: 29.0%; placebo: 40.0% (P = not
      significant). Adverse events were higher in everolimus-treated patients
      especially at the 4-mg/day dose, but there was no difference in the incidence of
      thrombocytopenia or leukopenia between all groups and renal function as
      determined by serum creatinine, and creatinine clearance remained stable to 36
      months in everolimus-treated patients. Mean cholesterol and triglycerides
      increased from baseline in all treatment groups, and maximum levels were seen at
      6 months. In conclusion, this study demonstrates that everolimus in combination
      with oral cyclosporine had an acceptable safety and tolerability profile, paving
      the way for additional studies in this transplant indication.

PMID- 16598778
TI  - Involvement of phosphatidylcholine-selective phospholipase C in activation of
      mitogen-activated protein kinase pathways in imidazoline receptor antisera
      selected protein.
AB  - Imidazoline receptor antisera-selected protein (IRAS) is considered as a
      candidate for the I1-imidazoline receptor (I1R), but the signaling pathway
      mediated by IRAS remains unknown. In our study, the signal transduction pathways
      of IRAS were investigated in CHO cells stably expressing IRAS (CHO-IRAS), and
      compared to the native I1R signaling pathways. Rilmenidine or moxonidine (10 nM
      100 microM), I1R agonists, failed to stimulate [35S]-GTPgammaS binding in CHO
      IRAS cell membrane preparations, suggesting that G protein may not be involved in
      IRAS signaling pathway. However, incubation of CHO-IRAS with rilmenidine or
      moxonidine for 5 min could induce an upregulation of phosphatidylcholine
      selective phospholipase C (PC-PLC) activity, and an increase in the accumulation
      of diacylglycerol (DAG), the hydrolysate of PC-PLC, in a concentration-dependent
      manner. The elevated activation of PC-PLC by rilmenidine or moxonidine (100 nM)
      could be blocked by efaroxan, a selective I1R antagonist. Cells treated with
      rilmenidine or moxonidine showed an increased level of extracellular signal
      regulated kinase (ERK) phosphorylation in a concentration-dependent manner, which
      could be reversed by efaroxan or D609, a selective PC-PLC inhibitor. These
      results suggest that the signaling pathway of IRAS in response to I1R agonists
      coupled with the activation of PC-PLC and its downstream signal transduction
      molecule, ERK. These findings are similar to those in the signaling pathways of
      native I1R, providing some new evidence for the relationship between I1R and
      IRAS.

PMID- 16598779
TI  - Schwann cells genetically engineered to express PSA show enhanced migratory
      potential without impairment of their myelinating ability in vitro.
AB  - Schwann cells, the myelin-forming cells of the PNS, are attractive candidates for
      remyelination therapy as they can remyelinate CNS axons. Yet their integration in
      CNS tissue appears hampered, at least in part, by their limited motility in the
      CNS environment. As the polysialylated (PSA) form of NCAM regulates migration of
      neural precursors in the CNS and is not expressed by developing Schwann cells, we
      investigated whether conferring sustained expression of PSA to Schwann cells
      derived from postnatal rats enhances their motility. Cells were transduced with a
      retrovirus encoding polysialyl-transferase STX, an enzyme that synthesizes PSA on
      NCAM. Migration of wild type and transduced cells expressing STX or the marker
      gene alkaline phosphatase was examined using a gap bridging assay in dissociated
      cells and by grafting cells in slice cultures of postnatal brain. Migration of
      PSA expressing cells was significantly increased in both models, as compared to
      control cells, and this effect was abolished by endoneuraminidase-N stripping of
      PSA. PSA-positive Schwann cells retained the ability to differentiate in vitro
      and expressed the Krox20 and P zero myelination markers. When grafted in neonatal
      cerebellar slices, STX-transduced cells started to myelinate Purkinje cell axons
      like control cells and make myelin internodes after 2 to 3 weeks. PSA was
      redistributed on the cell membrane and downregulated during differentiation in
      pure Schwann cell cultures and slice co-cultures. Thus, migratory properties of
      PNS myelin-forming cells within the CNS can be enhanced without altering their
      differentiation program. This finding may be beneficial for the development of
      remyelination therapies.

PMID- 16598780
TI  - Invasive aspergillosis in the recipients of liver retransplantation.
AB  - Retransplantation is a major risk factor for invasive aspergillosis in liver
      transplant recipients. However, the risk for invasive aspergillosis with time
      elapsed since retransplantation, clinical characteristics, and outcome of
      patients who develop this infection after retransplantation of the liver has not
      been defined. Patients comprised 17 liver retransplant recipients with invasive
      aspergillosis between 1990 and 2004. Retransplantation was considered early if it
      was performed within 30 days and late if performed after 30 days of the first or
      primary transplant. Retransplant recipients comprised 25% of all cases of
      invasive aspergillosis after liver transplantation. Fifty-three percent of the
      Aspergillus infections occurred within 30 days, and 76% within 90 days of
      retransplantation. In all, 53% (9/17) of the patients were late retransplant
      recipients. Late compared to early retransplant recipients with invasive
      aspergillosis were more likely to have central nervous system involvement with
      invasive aspergillosis (56% vs. 0%, P = 0.03). Mortality rate was 100% for late
      and 63% for early retransplant recipients with Aspergillus infections. In
      conclusion, time-varying risk for invasive aspergillosis after retransplantation
      has implications relevant for guiding antifungal prophylaxis. Given a greater
      risk for disseminated infection and poor outcome in late retransplant recipients
      with aspergillosis, potent and aggressive antifungal therapy should be considered
      upfront in these patients.

PMID- 16598781
TI  - Modulation of mouse RANKL gene expression by Runx2 and PKA pathway.
AB  - Runx2 regulates the target genes characteristic of osteoblastic phenotypes, while
      exerting diverse and sometimes controversial effects on osteoblastic cells
      depending on their differentiation stage. Receptor activator of nuclear factor
      kappaB (RANK) ligand (RANKL) is a membrane bound cytokine essential for
      osteo(chondro)clastogenesis. During endochondral ossification, while Runx2
      positive hypertrophic chondrocytes express RANKL, the steady-state expression of
      the RANKL gene in osteoblastic cells is, at later stages, kept at a relatively
      low level to sustain the established bone. The aim of this study was to elucidate
      the mechanism whereby Runx2 and the protein kinase A (PKA) pathway modulate RANKL
      expression, especially from the viewpoint of their functions in RANKL basic
      promoter activity and in chromatin structural changes in osteoblastic/stromal
      cells. Osteoblastic/stromal cell lines derived from normal and Runx2-deficient
      mice were used to analyze endogenous RANKL gene expression by real-time reverse
      transcription (RT)-PCR, the acetylation status of the H3 and H4 histone proteins
      associated with the 5'-flanking region of the RANKL gene by chromatin
      immunoprecipitation, and the exogenously transfected RANKL gene promoter activity
      both in the steady-state and under PKA-activated conditions. Here, we demonstrate
      that Runx2 suppresses steady-state RANKL gene expression by condensing chromatin,
      while showing a slightly positive effect on RANKL basic promoter activity.
      Besides acting through the CRE-like region (-0.96 kb) of the RANKL gene promoter,
      forskolin (FK) treatment transactivates the RANKL gene by antagonizing the
      function of Runx2, by reducing Runx2 mRNA expression and by opening the chromatin
      conformation far upstream (more than 40 kb) of the RANKL gene.

PMID- 16598783
TI  - Post-translational modification by O-GlcNAc: another way to change protein
      function.
AB  - Modification of intracellular proteins by the beta-linkage of the monosaccharide,
      N-acetylglucosamine to serine or threonine hydroxyls (O-GlcNAc) is abundant and
      reversible. Although many proteins bear this post-translational covalent
      modification, the changes in function of the proteins as a result of this
      modification are only starting to be understood. In this article, we describe how
      aspects of the flux from the glucose backbone to this modification are modified
      and how the cellular activity and content of the GC-box binding transcription
      factor, Sp1, is altered by O-glycosylation. The association of the enzyme that
      puts on the O-GlcNAc modification with the bi-functional enzyme that removes this
      modification is discussed relative to the transition between transcriptional
      repression and activation.

PMID- 16598782
TI  - Nuclease sensitive element binding protein 1 gene disruption results in early
      embryonic lethality.
AB  - Nuclease sensitive element binding protein 1 (NSEP1) is a member of the
      EFIA/NSEP1/YB-1 family of DNA-binding proteins whose members share a cold shock
      domain; it has also been termed DNA-binding protein B and Y box binding protein-1
      because of its recognition of transcriptional regulatory elements. In addition,
      NSEP1 functions in the translational regulation of renin, ferritin, and
      interleukin 2 transcripts, and our laboratory has reported that it plays a role
      in the biosynthesis of selenium-containing proteins. To test the functional
      importance of NSEP1 in murine embryonic development, we have utilized a clone of
      ES cells in which the NSEP1 gene had been disrupted by integration of a plasmid
      gene-trapping vector into the seventh exon. Injection of these cells into C57BL/6
      blastocysts resulted in 11 high percentage chimeric mice; crosses to wild type
      C57BL/6 mice generated 82 F1 agouti mice, indicating germ line transmission of
      the ES cell clone, but genotyping showed no evidence of the disrupted allele in
      any of these agouti offspring even though spermatozoa from four of five tested
      mice contained the targeted allele. Embryos harvested after timed matings of
      chimeric male mice demonstrated only the wildtype allele in 27 embryos tested at
      E7.5, E12.5, and E18.5. These results suggest that gene targeting of NSEP1
      induces a lethal phenotype in early embryos, due to either haploinsufficiency of
      NSEP1 or formation of a dominant negative form of the protein. In either case,
      these data indicate the functional importance of the NSEP1 gene in murine early
      embryonic development.

PMID- 16598784
TI  - Selection of liver-transplant candidates for adult-to-adult living donor liver
      transplantation as the only surgical option for end-stage liver disease.
AB  - The selection of living donor liver transplantation (LDLT) recipients in regions
      where deceased donor liver transplantation (DDLT) is rarely performed might be
      different from that in other centers at which LDLT is an alternative option to
      DDLT. Records of adult (age > or = 18 yr) patients referred to our center were
      reviewed to analyze the selection process of LDLT candidates. Among the 533 LDLT
      candidates, 165 (31%) were rejected due to recipient issues. Advanced
      hepatocellular carcinoma (HCC) was the most common reason for rejection (n = 55).
      Among the remaining recipients, 120 patients (22%) were rejected due to donor
      issues. LDLT was eventually performed in 249 (47%) of the evaluated recipients.
      There are few options for candidates who are unable to find live donors in
      regions where DDLT is unrealistic. A more effective and precise approach to
      recipient and donor evaluation should be pursued.

PMID- 16598785
TI  - Modulation by the steroid/thyroid hormone superfamily of TGF-beta-stimulated VEGF
      release from vascular smooth muscle cells.
AB  - We previously reported that transforming growth factor-beta (TGF-beta) stimulates
      the release of vascular endothelial growth factor (VEGF) from aortic smooth
      muscle A10 cells via activation of p38 mitogen-activated protein (MAP) kinase. In
      the present study, we investigated whether nuclear hormone receptor superfamily
      members affect TGF-beta-stimulated VEGF release from A10 cells. Retinoic acid or
      1,25-dihydroxyvitamin D3 enhanced TGF-beta-induced VEGF release in a
      concentration-dependent manner, whereas dexamethasone or corticosterone
      suppressed TGF-beta-induced VEGF release. 1,25-Dihydroxyvitamin D3 and TGF-beta
      stimulated phosphorylation of p38 MAP kinase in an additive manner. SB203580, an
      inhibitor of p38 MAP kinase, decreased the VEGF release induced by TGF-beta or
      1,25-dihydroxyvitamin D3. However, retinoic acid, dexamethasone, or
      corticosterone did not affect phosphorylation of p38 MAP kinase. These results
      indicate that retinoic acid, 1,25-dihydroxyvitamin D3, and glucocorticoids affect
      TGF-beta-stimulated VEGF release from aortic smooth muscle cells. The stimulatory
      effect of 1,25-dihydroxyvitamin D3 occurs, in part, via modification of TGF-beta
      induced activation of p38 MAP kinase.

PMID- 16598786
TI  - Retinoids directly activate the collagen X promoter in prehypertrophic
      chondrocytes through a distal retinoic acid response element.
AB  - Retinoids are essential for the terminal differentiation of chondrocytes during
      endochondral bone formation. This maturation process is characterized by
      increased cell size, expression of a unique extracellular matrix protein,
      collagen X, and eventually by mineralization of the matrix. Retinoids stimulate
      chondrocyte maturation in cultured cells and experimental animals, as well as in
      clinical studies of synthetic retinoids; furthermore, retinoid antagonists
      prevent chondrocyte maturation in vivo. However, the mechanisms by which
      retinoids regulate this process are poorly understood. We and others showed
      previously that retinoic acid (RA) stimulates expression of genes encoding bone
      morphogenetic proteins (BMPs), suggesting that retinoid effects on chondrocyte
      maturation may be indirect. However, we now show that RA also directly stimulates
      transcription of the collagen X gene promoter. We have identified three RA
      response element (RARE) half-sites in the promoter, located 2,600 nucleotides
      upstream from the transcription start site. These three half-sites function as
      two overlapping RAREs that share the middle half-site. Ablation of the middle
      half-site destroys both elements, abolishing RA receptor (RAR) binding and
      drastically decreasing RA stimulation of transcription. Ablation of each of the
      other two half-sites destroys only one RARE, resulting in an intermediate level
      of RAR binding and transcriptional stimulation. These results, together with our
      previously published data, indicate that retinoids stimulate collagen X
      transcription both directly, through activation of RARs, and indirectly, through
      increased BMP production.

PMID- 16598787
TI  - Are there morally acceptable alternatives to blastocyst derived ESC?
AB  - ESC derivation, use and SCNT have raised many moral and ethical issues. In this
      opinion piece I have focused on the argument that morally less ambiguous
      alternatives to ESC derived from the ICM of blastocysts exist. These
      possibilities range from using multiple adult stem cell populations each of which
      is uniquely suited for a particular disease target or identifying adult ESC-like
      populations, using transdifferentiated ESC-like cells or alternate methods of
      deriving ESC. I suggest that while it is important to support such efforts,
      current results do not provide sufficient compelling data to allow one to stop
      the use of ESC and perhaps adult cells will never be a reliable alternative. All
      options need to be fully explored and decisions need to be made with scientific
      rigor and respect for each individual's moral compass.

PMID- 16598788
TI  - Selective and nonselective benzodiazepine agonists have different effects on
      motor cortex excitability.
AB  - Transcranial magnetic stimulation (TMS) is a useful method to study
      pharmacological effects on motor cortex excitability. Zolpidem is a selective
      agonist of the benzodiazepine receptor subtype BZ1 and has a distinct
      pharmacological profile compared to diazepam. To study the different effects of
      these two drugs on the cortical inhibitory system, TMS was performed before and
      after administration of a single oral dose of zolpidem (10 mg) and diazepam (5
      mg) in six healthy volunteers. TMS tests included the determination of resting
      and active motor threshold (MT) and measurements of the amplitudes of motor
      evoked potentials, intracortical facilitation (ICF), short-latency intracortical
      inhibition (SICI), and long-latency intracortical inhibition (LICI), and
      determination of the cortical silent period (CSP). Both drugs were without effect
      on the active or resting MT and decreased the ICF. Prolongation of the CSP and
      enhancement of LICI only in the presence of zolpidem point to a specific BZ1
      related mechanism underlying the long-lasting component of cortical inhibition.
      This selective modulation of the CSP and the LICI points to a specific role of
      BZ1 receptors in the control of inhibitory neuronal loops within the primary
      motor cortex.

PMID- 16598789
TI  - Inhibition of PP2A, but not PP5, mediates p53 activation by low levels of okadaic
      acid in rat liver epithelial cells.
AB  - The microbial toxin okadaic acid (OA) specifically inhibits PPP-type ser/thr
      protein phosphatases. OA is an established tumor promoter with numerous cellular
      effects that include p53-mediated cell cycle arrest. In T51B rat liver epithelial
      cells, a model useful for tumor promotion studies, p53 activation is induced by
      tumor-promoting (low nanomolar) concentrations of OA. Two phosphatases sensitive
      to these concentrations of OA, PP2A and protein phosphatase 5 (PP5), have been
      implicated as negative regulators of p53. In this study we examined the
      respective roles of these phosphatases in p53 activation in non-neoplastic T51B
      cells. Increases in p53 activity were deduced from levels of p21 (cip1) and/or
      the rat orthologue of mdm2, two p53-regulated gene products whose induction was
      blocked by siRNA-mediated knockdown of p53. As observed with 10 nM OA, both
      phospho-ser15-p53 levels and p53 activity were increased by 10 microM fostriecin
      or SV40 small t-antigen. Both of these treatments selectively inhibit PP2A but
      not PP5. siRNA-mediated knockdown of PP2A, but not PP5, also increased p53
      activity. Finally, adenoviral-mediated over-expression of an OA-resistant form of
      PP5 did not prevent increased phospho-ser15-p53, p53 protein, or p53 activity
      caused by 10 nM OA. Together these results indicate that PP5 blockade is not
      responsible for OA-induced p53 activation and G1 arrest in T51B cells. In
      contrast, specific blockade of PP2A mimics p53-related responses to OA in T51B
      cells, suggesting that PP2A is the target for this response to OA.

PMID- 16598790
TI  - Utrophin is a calpain substrate in muscle cells.
AB  - Calpains are Ca2+ -dependent cytosolic cysteine proteases that participate in the
      pathology of Duchenne muscular dystrophy (DMD). Utrophin is a functional homolog
      of dystrophin that partially compensates for dystrophin deficiency in myofibers
      of mdx mice. In this study, we investigated the susceptibility of utrophin to
      cleavage by calpain in vitro and in muscle cells. We found that utrophin is a
      direct in vitro substrate of purified calpain I and II. Cleavage of utrophin by
      calpain I or II generates specific degradation products that are also found in
      cultured control and DMD myotubes under conditions with elevated intracellular
      Ca2+ levels. In addition, we showed that activation of cellular calpains by Ca2+
      ionophore treatment reduces utrophin protein levels in muscle cells and that
      calpain inhibition prevents this Ca2+ -induced reduction in utrophin levels.
      These observations suggest that, beside its known effect on general muscle
      protein degradation, calpain contributes to DMD pathology by specifically
      degrading the compensatory protein utrophin.

PMID- 16598791
TI  - Integrin signaling and cell spreading mediated by phorbol 12-myristate 13-acetate
      treatment.
AB  - Spreading of SNU16mAd gastric carcinoma cells was previously shown to be
      regulated via a signaling network from transforming growth factor beta1
      (TGFbeta1) to integrins signaling, through a mediation of protein kinase C delta
      (PKCdelta). However, in the previous study, the roles of PKCdelta appeared
      complicated. In this study to clarify the roles of PKCdelta in the spreading of
      the gastric carcinoma cells, we questioned if PKC activation via phorbol 12
      myristate 13-acetate (PMA) treatment could mimic the TGFbeta1 effects. An acute
      PMA treatment increased phosphorylations of focal adhesion (FA) kinase, paxillin,
      c-Src, and cofilin, just as TGFbeta1 did. Furthermore, cell spreading mediated by
      TGFbeta1- or acute PMA treatment correlated with activation of RhoA, which
      regulates actin reorganization and FA formation. However, stress fiber formation
      was prominent in TGFbeta1-treated cells, compared to cortical actin organization
      in PMA-treated cells. Altogether, these observations indicate that acute PMA
      treatment could mimic the TGFbeta1 mechanisms for cell spreading through subtly
      different effects on actin reorganization.

PMID- 16598792
TI  - Impact of model for end-stage liver disease (MELD) score on prognosis after
      hepatectomy for hepatocellular carcinoma on cirrhosis.
AB  - The objective of this study was to predict postoperative liver failure and
      morbidity after hepatectomy for hepatocellular carcinoma (HCC) with cirrhosis.
      The model for end-stage liver disease (MELD) score is currently accepted as a
      disease severity index of cirrhotic patients awaiting liver transplantation;
      however, its impact on prognosis after resection of HCC on cirrhosis has never
      been investigated. One hundred fifty-four cirrhotic patients resected in a
      tertiary care setting for HCC were retrospectively analyzed. For each patient,
      the MELD score was calculated and related to postoperative liver failure and
      complications (morbidity). Hospital stay and 1-year survival was also
      investigated. MELD accuracy in predicting postoperative liver failure and
      morbidity of cirrhotic patients was assessed using receiver operating
      characteristic (ROC) analysis. Eleven patients (7.1%) experienced postoperative
      liver failure leading to death or transplantation. ROC analysis identified
      cirrhotic patients with a MELD score equal to or above 11 at high risk for
      postoperative liver failure (area under the curve [AUC] = 0.92, 95% confidence
      interval [CI] = 0.87-0.96; sensitivity = 82%; specificity = 89%). Forty-six
      patients (29.9%) developed at least 1 postoperative complication: ROC analysis
      identified patients with a MELD score equal to or above 9 at major risk for
      postoperative complications (AUC = 0.85, 95% CI = 0.78-0.89; sensitivity = 87%;
      specificity = 63%). Cirrhotic patients with MELD score below 9 had no
      postoperative liver failure and low morbidity (8.1%). In conclusion, the MELD
      score can accurately predict postoperative liver failure and morbidity of
      cirrhotic patients referred for resection of HCC and should be used to select the
      best candidates for hepatectomy.

PMID- 16598793
TI  - Experimental design principles for isotopically instationary 13C labeling
      experiments.
AB  - 13C metabolic flux analysis (MFA) is a well-established tool in Metabolic
      Engineering that found numerous applications in recent years. However, one strong
      limitation of the current method is the requirement of an-at least approximate
      isotopic stationary state at sampling time. This requirement leads to a principle
      lower limit for the duration of a 13C labeling experiment. A new methodological
      development is based on repeated sampling during the instationary transient of
      the 13C labeling dynamics. The statistical and computational treatment of such
      instationary experiments is a completely new terrain. The computational effort is
      very high because large differential equations have to be solved and, moreover,
      the intracellular pool sizes play a significant role. For this reason, the
      present contribution works out principles and strategies for the experimental
      design of instationary experiments based on a simple example network. Hereby, the
      potential of isotopically instationary experiments is investigated in detail.
      Various statistical results on instationary flux identifiability are presented
      and possible pitfalls of experimental design are discussed. Finally, a framework
      for almost optimal experimental design of isotopically instationary experiments
      is proposed which provides a practical guideline for the analysis of large-scale
      networks.

PMID- 16598794
TI  - Development and calibration of a nitrification PDE model based on experimental
      data issued from biofilter treating drinking water.
AB  - To remove ammonia for production of drinking water, nitrification can be
      performed in a bio-filter. At least 1 month is necessary to capture from the
      groundwater and then grow a sufficient amount of nitrifying bacteria to reach the
      desired removal efficiency. Improving start-up of bio-filters at low substrate
      concentration is therefore a major challenge. In this connection, it is important
      to develop appropriate models for designing, monitoring or analysing biofilm
      systems during start-up or following disinfection events. This study discusses
      the development and calibration of a nitrification PDE model which reflects the
      compromise between the complexity associated with the description of the full
      physical and biochemical mechanisms and the search for a simplified model with
      identifiable parameters. This model takes only the relevant phenomena
      (considering the full operating range) into account. The validity of the
      calibrated model has been evaluated through experiments under very different
      operational conditions, at the laboratory and under real industrial conditions,
      involving the full upstream chain of water treatment (iron oxidation and sand
      filter).

PMID- 16598796
TI  - Determination of the decay rate of nitrifying bacteria.
AB  - The growth and decay of nitrifying organisms determines the amount of nitrifying
      bacteria in activated sludge systems. The growth rate of the nitrifying organisms
      is reasonable, well defined, and studied, while the decay rate is still rather
      uncertain. Experiments in previous studies were over periods up to 14 days and
      obtained results were not confirmed. Contradicting decay rates of nitrifiers in
      different bacterial communities is reported. No differentiation between ammonia
      and nitrite oxidizers was made. Therefore, in this studyper day the decay rate of
      the nitrifying organisms was studied. The starvation condition (aerobic, anoxic,
      or anaerobic), temperature, type of bacterial community, and the presence of
      higher organisms are the main aspects that were investigated. A simple and
      reliable method (adapted from previous studies) for determining the decay rate of
      nitrifying organisms under different starvation conditions and different
      temperatures was developed. The test procedure has been used for determining the
      decay rate of ammonium and nitrite oxidizing bacteria in an enriched nitrifying
      culture and in activated sludge. The test was successfully applied at starvation
      periods up to 30 days. The decay rate of the enriched culture of nitrifiers was
      very low compared to values for nitrifiers in activated sludge. The decay rate of
      the nitrifiers in activated sludge was found to be to 0.2, 0.1, and 0.06 per day
      for aerobic, anoxic, and anaerobic conditions, respectively. The decay rate of
      ammonia oxidizers and nitrite oxidizers was the same at the corresponding
      conditions.

PMID- 16598795
TI  - Combining caspase and mitochondrial dysfunction inhibitors of apoptosis to limit
      cell death in mammalian cell cultures.
AB  - Apoptosis is now recognized as a significant problem in mammalian cell culture.
      Therefore, in this study, a single gene and multigene approach to inhibit
      apoptosis has been examined. Stable Chinese hamster ovary (CHO) cell lines were
      generated to overexpress different single, dual, and triple combinations of three
      apoptosis inhibitor genes. Two upstream inhibitors involved in the mitochondrial
      pathway, Bcl-X(L) and Aven, were expressed in addition to a downstream inhibitor
      of caspases. The caspase inhibitor, a variant of XIAP containing only the caspase
      inhibitory BIR domains (XIAP-BIRs), has been shown previously to enhance
      viabilities in mammalian cultures. Stable clonal cell lines were generated and
      tested for three apoptotic insults: Sindbis virus infection, the chemical reagent
      etoposide, and spent medium. For all single gene experiments, the Bcl-X(L)
      containing cell lines provided superior protection to either the Aven- or XIAP
      BIRs-containing cell lines following initial exposure to the insults. However,
      the cell lines expressing two or more anti-apoptosis proteins were more effective
      at inhibiting cell death than those expressing just one anti-apoptosis gene. The
      cell lines overexpressing Bcl-X(L) in combination with XIAP-BIRs were especially
      effective in delaying cell death for all three apoptotic insults. Expression of
      all three anti-apoptosis genes in concert was only slightly more effective than
      using Bcl-X(L) and XIAP-BIRs for some insults. During exposure to spent medium,
      CHO-BIRS + Aven + BclX(L) was the best inhibitor of apoptosis (IAP) initially,
      whereas CHO-BIRs + BclX(L) was particularly effective at later times of the
      experiment. In conclusion, the utilization of a mitochondrial dysfunction
      inhibitor used in combination with a caspase inhibitor was more effective in
      thwarting the progression of apoptosis than either inhibitor expressed
      individually. Thus, the concurrent expression of multiple apoptosis inhibitors
      may be the most effective strategy to increase survival of mammalian cells in
      culture.

PMID- 16598797
TI  - Diffusivity of oxygen in aerobic granules.
AB  - This work for the first time estimated apparent oxygen diffusivity (D(app)) of
      two types of aerobic granules, acetate-fed and phenol-fed, by probing the
      dissolved oxygen (DO) level at the granule center with a sudden change in the DO
      of the bulk liquid. With a high enough flow velocity across the granule to
      minimize the effects of external mass transfer resistance, the diffusivity
      coefficients of the two types of granules were estimated with reference to a one
      dimensional diffusion model. The carbon source has a considerable effect on the
      granule diameter (d) and the oxygen diffusivity. The diffusivity coefficients
      were noted 1.24-2.28 x 10(-9) m2/s of 1.28-2.50 mm acetate-fed granules, and 2.50
      7.65 x 10(-10) m2/s of 0.42-0.78 mm phenol-fed granules. Oxygen diffusivity
      declined with decreasing granule diameter, in particular, the diffusivity of
      acetate-fed granules is proportional to the size, whereas the diffusivity of
      phenol-fed granules is proportional to the square of granule diameter. The
      existence of large pores in granule, evidenced by FISH-CLSM imaging, was proposed
      to correspond to the noted size-dependent oxygen diffusivity. The phenol-fed
      granules exhibited a higher excellular polymer (ECP) content than the acetate-fed
      granules, hence yielding a lower oxygen diffusivity.

PMID- 16598798
TI  - A challenge to chemical intuition: donor-acceptor interactions in H3B-L and H2B+
      L (L=CO; EC5H5, E=N-Bi).
AB  - The equilibrium geometries and bond energies of the complexes H(3)B-L and
      H(2)B(+)-L (L=CO; EC(5)H(5): E=N, P, As, Sb, Bi) have been calculated at the
      BP86/TZ2P level of theory. The nature of the donor-acceptor bonds was
      investigated by energy decomposition analysis (EDA). The bond strengths of H(3)B
      L have the order CO>N>P>As>Sb>Bi. The calculated values are between D(e)=37.1
      kcal mol(-1) for H(3)B-CO and D(e)=6.9 kcal mol(-1) for H(3)B-BiC(5)H(5). The
      bond dissociation energies of the cations H(2)B(+)-CO and H(2)B(+)-EC(5)H(5) are
      larger than for H(3)B--L, particularly for complexes of the heterobenzene
      ligands. The calculated values are between D(e)=51.9 kcal mol(-1) for H(2)B(+)-CO
      and D(e)=122.1 kcal mol(-1) for H(2)B(+)-NC(5)H(5). The trend of the BDE of
      H(2)B(+)-CO and H(2)B(+)-EC(5)H(5) is N>P>As>Sb>Bi>CO. A surprising result is
      found for H(2)B(+)-CO, which has a significantly stronger and yet substantially
      longer bond than H(3)B-CO. The reason for the longer but stronger bond in
      H(2)B(+)-CO compared with that in H(3)B-CO comes mainly from the change in
      electrostatic attraction and pi bonding at shorter distances, which increases
      more in the neutral system than in the cation, and to a lesser extent from the
      deformation energy of the fragments. The H(2)B(+)<--NC(5)H(5) pi( perpendicular)
      donation plays an important role for the stronger interactions at shorter
      distances compared with those in H(3)B-NC(5)H(5). The attractive interaction in
      H(2)B(+)--CO further increases at bond lengths that are shorter than the
      equilibrium value, but this is compensated by the energy which is necessary to
      deform BH(2) (+) from its linear equilibrium geometry to the bent form in the
      complex. The EDA shows that the contributions of the orbital interactions to the
      donor-acceptor bonds are always larger than the classical electrostatic
      contributions, but the latter term plays an important role for the trend in bond
      strength. The largest contributions to the orbital interactions come from the
      sigma orbitals. The EDA calculations suggest that heterobenzene ligands may
      become moderately strong pi donors in complexes with strong Lewis acids, while CO
      is only a weak pi donor. The much stronger interaction energies in H(2)B(+)
      EC(5)H(5) compared with those in H(3)B-EC(5)H(5) are caused by the significantly
      larger contribution of the pi(perpendicular) orbitals in H(2)B(+)-EC(5)H(5) and
      by the increase of the binding interactions of the sigma+pi( parallel) orbitals.

PMID- 16598799
TI  - A counterintuitive structural effect of metal-metal bond protonation and its
      electronic underpinnings.
AB  - Protonation across the metal-metal bond in the complexes [(CO)(2)M(mu-dppm)(mu
      PtBu(2))(mu-H)M(CO)(2)] (M=Fe or Ru, dppm=Ph(2)PCH(2)PPh(2)) induces M-M bond
      shortening of up to about 0.05 A. DFT calculations on simplified iron models
      reproduce this trend well. Conversely, the computations show that the M-M
      distance in the dimer [{Cp*Ir(CO)}(2)] lengthens with two consecutive
      protonations, but there are no crystal structure determinations to highlight the
      effects on the Ir-Ir bond. DFT calculations and the analogous cobalt system
      confirm that the transformation of a two-electron, two-center (2e-2c) bond into a
      2e-3c bond is accompanied by the predicted elongation. An MO analysis indicated
      similar nature and evolution of the M-M bonding these cases. In particular, the
      HOMOs of the mono-hydrido cations [Cp(CO)M(mu-H)M(CO)Cp](+) (M=Ir, Co) have
      evident M-M bent-bond character, and hence subsequent protonation invariably
      causes a decrease in the bond index. The Fe(2) and Co(2) systems have also been
      analyzed with the quantum theory of atoms in molecules (QTAIM) method, but in no
      case was an M-M bond critical point located unless an artificially shorter M-M
      distance was imposed. However, the trends for the atoms-in-molecules (AIM) bond
      delocalization indexes delta(M-M) confirm the overall M-M bond weakening on
      protonation. In conclusion, all the computational results for the iron system
      indicate that the paradigm of a direct correlation between bond strength and
      distance is not always applicable. This is attributable to a very flat potential
      energy surface and various competing effects imposed by the bridging ligands.

PMID- 16598800
TI  - One-pot enantioselective aziridination of olefins catalyzed by a copper(I)
      complex of a novel diimine ligand by using PhI(OAc)(2) and sulfonamide as nitrene
      precursors.
AB  - A novel chiral C(2)-symmetric 1,4-diamine with multistereogenic centers at the
      backbone of the ligand has been synthesized from cheap natural product D-mannitol
      through multistep transformations. Its diimine derivative (3 a) was found to be
      highly effective for the enantioselective control of the copper-catalyzed
      asymmetric aziridination of olefin derivatives with PhI==NTs as the nitrene
      source, affording the corresponding N-sulfonylated azirindine derivatives in good
      to excellent yields with up to 99 % ee (ee=enantiomeric excess). The catalyst
      system discovered in the present work was also extended to a one-pot
      enantioselective aziridination by using sulfonamide/iodobenzene diacetate as the
      nitrene source. In this case, most reactions proceeded smoothly to give the
      corresponding products in moderate yields with good to excellent enantiomeric
      excesses (75-96 % ee).

PMID- 16598801
TI  - Photosensitized oxidation of sulfides: discriminating between the singlet-oxygen
      mechanism and electron transfer involving superoxide anion or molecular oxygen.
AB  - The oxidation of diethyl and diphenyl sulfide photosensitized by
      dicyanoanthracene (DCA), N-methylquinolinium tetrafluoroborate (NMQ(+)), and
      triphenylpyrylium tetrafluoroborate (TPP(+)) has been explored by steady-state
      and laser flash photolysis studies in acetonitrile, methanol, and 1,2
      dichloroethane. In the Et(2)S/DCA system sulfide-enhanced intersystem crossing
      leads to generation of (1)O(2), which eventually gives the sulfoxide via a
      persulfoxide; this mechanism plays no role with Ph(2)S, though enhanced formation
      of (3)DCA has been demonstrated. In all other cases an electron-transfer (ET)
      mechanism is involved. Electron-transfer sulfoxidation occurs with efficiency
      essentially independent of the sulfide structure, is subject to quenching by
      benzoquinone, and does not lead to Ph(2)SO cooxidation. Formation of the radical
      cations R(2)S(*+) has been assessed by flash photolysis (medium-dependent yield,
      dichloroethane>>CH(3)CN>CH(3)OH) and confirmed by quenching with 1,4
      dimethoxybenzene. Electron-transfer oxidations occur both when the superoxide
      anion is generated by the reduced sensitizer (DCA(*-), NMQ(*)) and when this is
      not the case (TPP(*)). Although it is possible that different mechanisms operate
      with different ET sensitizers, a plausible unitary mechanism can be proposed.
      This considers that reaction between R(2)S(*+) and O(2)(*-) mainly involves back
      electron transfer, whereas sulfoxidation results primarily from the reaction of
      the sulfide radical cation with molecular oxygen. Calculations indeed show that
      the initially formed fleeting complex RS(2)(+)...O-O(*) adds to a sulfide
      molecule and gives strongly stabilized R(2)S-O(*)-(+)O-SR(2) via an accessible
      transition state. This intermediate gives the sulfoxide, probably via a radical
      cation chain path. This mechanism explains the larger scope of ET sulfoxidation
      with respect to the singlet-oxygen process.

PMID- 16598802
TI  - Sensitive and selective photoinduced-electron-transfer-based sensing of
      alkylating agents.
AB  - Photoinduced-electron-transfer (PET)-based chemosensing is a very elegant way of
      reporting the presence of a guest species in solution. This method was
      successfully applied for the detection of different ionic species, such as
      cations, anions, and protons. Herein, we report on the application of the PET
      chemosensing concept for the efficient and selective detection of different
      alkylating agents. 2-(2-Dimethylaminoethyl)benzo[de]isoquinoline-1,3-dione (1)
      was found to be a highly selective and effective PET chemosensor that turns
      luminescent upon reacting with different alkylating agents. This PET-based system
      detected even rather weak alkylating agents, such as dichloromethane. A PET-based
      sensor that consists of 1 as the active component could detect rather low
      concentrations of alkylating agents in solution and in the gas phase.

PMID- 16598803
TI  - Controlled assembly of a heterogeneous single-site ethylene trimerization
      catalyst as probed by X-ray absorption spectroscopy.
AB  - X-ray absorption spectroscopy at the Cr K- and L(2,3)-edges was used to study the
      assembling process of a heterogeneous Cr-based single-site catalyst. The starting
      point was a Phillips-type system with monochromate species anchored on a silica
      surface, which was first reduced to a variety of different surface Cr(II)
      species. The reduced sample was modified with a 1,3,5-tribenzylhexahydro 1,3,5
      triazine (TAC) ligand in the presence of CH(2)Cl(2) as solvent to yield a
      heterogeneous single-site Cr-based catalyst active in the trimerization of
      ethylene. The molecular structure of the resultant catalytic material consists of
      distorted octahedral Cr(III) species. The extended X-ray absorption fine
      structure (EXAFS) spectroscopy fitting procedure in R space up to 2.5 A showed
      that the synthesis leads to coordination with a TAC ligand. The fit also shows
      that it was possible to complete the six-fold environment around Cr(III) with two
      oxygen atoms and one chloride ligand. This chloride ligand is formed in a redox
      process from the solvent and is responsible for the oxidation of surface Cr(II)
      to Cr(III). The obtained geometry and the local environment of the surface
      complex are discussed in light of its homogeneous counterpart and confirm the
      single-site characteristics of the prepared catalytic material.

PMID- 16598804
TI  - Food chemistry links chemistry with biology and medicine. Proceedings of the
      International Symposium, Wurzburg, Germany, October 12, 2005.

PMID- 16598805
TI  - Product-oriented flavor research: learnings from the past, visions for the
      future.
AB  - In the past flavor research and the development of new flavorings were constantly
      driven by the interaction of flavor analysis, structure elucidation, and chemical
      synthesis accompanied by sensory. Highly potent flavor compounds were identified
      in numerous food products and helped to establish a powerful toolbox for
      flavorists. Nowadays we experience the merging of various scientific disciplines,
      for example medicine, biology, chemistry, and various technologies in the field
      of flavor research, which shows direct impact on our understanding of flavors. At
      the same time modern life has profoundly changed our eating habits. This
      situation generates new challenges for product development teams, which represent
      all facets of technologies. This paper will illustrate different examples for the
      evolution of product-oriented flavor research and future trends.

PMID- 16598806
TI  - Anti-human immunodeficiency virus activity of 3,4,5-tricaffeoylquinic acid in
      cultured cells of lettuce leaves.
AB  - 3,4,5-Tricaffeoylquinic acid (TCQA) that is not found in intact plant of lettuce
      leaves was isolated from the cultured cells. The intact plant produced chicoric
      acid (dicaffeoyl tartaric acid: L-CCA) as well as chlorogenic acid (3
      caffeoylquinic acid: 3-CQA) as the major metabolites. After subculturing of the
      cells for 40 days, the amount of 3,4,5-TCQA reached to 0.14 mg/g fresh weight.
      The inhibitory effect of 3,4,5-TCQA for human immunodeficiency virus (HIV) Type 1
      integrase was assayed. Anti-HIV activity using HIV and MT-2 cells was 1.15 microM
      and IC(50) against HIV integrase was 0.063 microM whereas cell toxicity of this
      chemical was expressed as 5% death of all living cells to be 18.4 microM. The HIV
      inhibitory effect of 3,4,5-TCQA was the highest in values among L-CCA, and other
      dicaffeoylquinic acids. This data will provide a new possibility for creating a
      new drug design for HIV.

PMID- 16598807
TI  - Fusarium mycotoxins and ochratoxin A in cereals and cereal products: results from
      the Bavarian Health and Food Safety Authority in 2004.
AB  - Results from the Bavarian Health and Food Safety Authority on contamination of
      cereals and cereal products from the Bavarian market with the mycotoxins
      deoxynivalenol (DON), zearalenone (ZEA), and ochratoxin A (OTA) and of maize meal
      and semolina with fumonisins (FUM) in the year 2004 are presented. Contamination
      rates and levels of DON, ZEA, and OTA were low and did not exceed the maximum
      levels. However, a 92% contamination rate and high levels of FUM in maize meal
      and semolina were measured. Contamination levels of mycotoxins are discussed and
      evaluated with respect to possible health implications for consumers.

PMID- 16598808
TI  - Cytotoxic and antimitotic effects of N-containing Monascus metabolites studied
      using immortalized human kidney epithelial cells.
AB  - Recently the first Monascus metabolites with a pyridine ring were detected, the
      monascopyridines A and B. They are formally dehydrogenated derivatives of the red
      rice pigments rubropunctamine and monascorubramine. Because of their structural
      similarity, the toxicological effects of these secondary metabolites were studied
      using immortalized human kidney epithelial cells. The cytotoxicity was determined
      with the following different endpoint detection methods: metabolic activity,
      trypan blue exclusion, and electronic cell counting. The compounds led to EC(50)
      values between 11 and 31 micromol/L but the pigments caused a stronger reduction
      of the cell viability. Also, the apoptotic potential was examined by measuring
      caspase 3 activity and detecting apoptotic bodies, but none of the tested
      compounds induced apoptosis. All four substances caused a rise of the mitotic
      index to about 9% (100 micromol/L monascopyridine A and B) and 20% (25 micromol/L
      rubropunctamine and monascorubramine). The significant decrease of the ratio of
      cells in the ana- and telophase to cells in the prometa- and metaphase proved a
      stop of the mitosis at the meta- to anaphase control point. The compounds caused
      mitotic arrest and the formation of structural damages like c-mitosis through
      interaction with the mitotic spindle. These effects point to an aneuploidy
      inducing potential, which is linked to cancer formation.

PMID- 16598809
TI  - Detection of DNA-bound advanced glycation end-products by immunoaffinity
      chromatography coupled to HPLC-diode array detection.
AB  - Sugars and sugar degradation products are formed during food processing, but also
      endogenously in vivo. In vitro, nucleosides and DNA react readily with these
      carbonyl compounds during the formation of the two diastereomers of N(2)
      carboxyethyl-2'-deoxyguanosine (CEdG(A,B)), leading to a loss of DNA integrity.
      Only little is known about DNA glycation in vivo and about the influence of
      nutrition on CEdG formation. In this study, we developed a sensitive method to
      analyze DNA glycation by HPLC. For this purpose, immunoaffinity chromatography
      (IAC) using a polyclonal antibody against N(2)-carboxyethylguanine (CEguanine)
      was coupled to HPLC-DAD. In some samples, peak identity was confirmed by LC
      MS/MS. The recovery of CEguanine from the IAC columns was 52.5% +/- 3.6 (n = 4).
      Thus, it was possible for the first time to detect CEdG(A,B), N(2)
      carboxyethylguanosine (CEG(A,B)), and CEguanine in 11 human urine samples.
      However, due to imprecision of IAC, valid quantification of the adducts could not
      be achieved. Furthermore, CEdG was also detected in the DNA of cultured human
      smooth muscle cells (SMCs) and bovine aorta endothelium cells (BAECs). In BAECs,
      CEdG(A,B) were found by HPLC-DAD and LC-MS/MS after immunoaffinity purification,
      whereas in SMCs DNA-advanced glycation end-products were only detected with the
      more sensitive LC-MS/MS method.

PMID- 16598810
TI  - Genotoxicity of glycidamide in comparison to (+/-)-anti-benzo[a]pyrene-7,8
      dihydrodiol-9,10-epoxide and alpha-acetoxy-N-nitroso-diethanolamine in human
      blood and in mammalian V79-cells.
AB  - Genotoxic activity of glycidamide (GA) was investigated in comparison to that of
      the known carcinogens (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide ((+/
      )-BPDE) and alpha-acetoxy-N-nitroso-diethanolamine (alpha-A-NDELA), using the
      hypoxanthine-phosphoribosyl-transferase (hPRT) gene mutation assay with V79
      mammalian cells and modified alkaline single cell gel electrophoresis (alkaline
      comet assay with and without treatment of cells with formamido-pyrimidine-DNA
      glycosylase (FPG)) in lymphocytes from human whole blood. As shown earlier, GA
      induced significant DNA damage in lymphocytes from treated whole blood at > or =
      300 microM (4 h) (Baum et al., Mutat. Res. 2005, 580, 61-69). In the present
      study, using the alkaline comet assay with FPG treatment, increased formation of
      DNA strand breaks was observed in lymphocytes treated with GA (10 microM; 4 h).
      alpha-A-NDELA and (+/-)-BPDE were genotoxic at 10-30 microM (1 h). Genotoxic
      activity of these compounds was not enhanced after FPG treatment. FPG treatment
      thus offers an enhanced sensitivity of DNA damage detection for genotoxic
      compounds with preference for N(7)- resp. N(3)-purine alkylation. In the hPRT
      assay with V79 cells, mutagenic activity of (+/-)-BPDE became significant at > or
      = 3 microM (24 h). For alpha-A-NDELA significant activity was observed at
      greater, not dbl 10 microM (24 h). As previously observed, GA was considerably
      less effective, inducing significant mutagenicity roughly at about 80-300-fold
      higher concentrations (800 microM; 24 h) (Baum et al., Mutat. Res. 2005, 580, 61
      69).

PMID- 16598811
TI  - Evaluation of electrospray-tandem mass spectrometry for the detection of
      phenylketonuria and other rare disorders.
AB  - Since a few years ESI-MS/MS has been employed for the simultaneous detection of a
      wide range of inborn errors of metabolism. The screening center North at the
      Hamburg University Medical Center processes 40-50,000 samples per year. To assess
      current developments in neonatal screening, the Northern German Working Group on
      Neonatal Screening consisting of health care providers, metabolic centers, and
      screening laboratories was founded. Based on current literature and experience
      four categories of diseases were established. The first three categories were
      recommended for screening under constant scientific evaluation, while glutaric
      aciduria II, beta-ketothiolase deficiency, short-chain acylCoA dehydrogenase
      deficiency, and homocystinuria were not included in the screening program. In
      contrast, general screening for phenylketonuria (PKU) remains undisputed and
      MS/MS screening reduced false positives by simultaneously detecting phenylalanine
      and tyrosine. Recently, (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH(4))
      sensitive PKU has been discovered. We were able to demonstrate that BH(4)
      treatment without dietary restrictions may be sufficient for certain BH(4)
      responsive PKU patients. In general, MS/MS provides a potential to rapidly screen
      for a wide variety of rare metabolic disorders but a close cooperation between
      scientists and metabolic doctors is required to constantly evaluate results in
      terms of improving the outcome of patients.

PMID- 16598813
TI  - Thermal degradation kinetics of isoflavone aglycones from soy and red clover.
AB  - Driven by their beneficial effects on human metabolism, isoflavonoids have gained
      considerable importance reflected by an increased number of isoflavone-rich
      foods, food supplements and pharmaceutical products on the market, mainly derived
      from soy and red clover. While it is well known that the genuine isoflavone
      pattern will be altered during processing, data on aglycone stability are rare.
      Therefore, a thorough study into the thermal sensitivities of biochanin A,
      daidzein, formononetin, flavone, genistein, glycitein and isoflavone was
      performed. Samples were heated at 150 degrees C over a period of 7 h at three
      different pH values, and degradation of the aglycones was monitored by HPLC-DAD
      analyses. Therefrom, structure-related stability characteristics could be
      established. While virtually no decay was observed at pH 7.0 and 5.6, degradation
      was most prominent at pH 3. 1. Individual aglycone retention was further
      dependent on heating time with daidzein being the most labile compound after any
      time interval. Curve fitting of the data revealed first-order degradation
      kinetics for flavone and glycitein, while the remaining aglycones exhibited a
      sigmoidal degradation pattern.

PMID- 16598814
TI  - Stimulation of estradiol glucuronidation: a protective mechanism against
      estradiol-mediated carcinogenesis?
AB  - 17beta-Estradiol (E2) and its catechol and methoxy metabolites are believed to
      play important roles in the mechanism of E2-mediated tumor formation. Because
      conjugation with glucuronic acid lowers tissue levels by facilitating excretion,
      we have determined the kinetic parameters of the glucuronidation of E2, estrone
      (E1), and seven phase I metabolites using human liver microsomes. The catechol
      estrogens 2- and 4-hydroxy-E2/E1 exhibited the highest clearance, exceeding that
      of E2, E1, and the methoxy metabolites by factors of 6-44. Homotropic activation
      kinetics were observed for the 3-glucuronidation of E2 but not for any of the
      metabolites. None of the metabolites affected the kinetics of the 3
      glucuronidation of E2. In contrast, the isoflavone daidzein stimulated the
      formation of E2-3-glucuronide, as has been reported previously. This heterotropic
      activation by daidzein appears to be specific for the glucuronidation of E2
      because daidzein did not affect the glucuronidation of the 2- and 4-hydroxy
      metabolites of E2. However, daidzein may lower the glucuronidation of 2-methoxy
      E2 in vivo due to its preferential glucuronidation. The decreased tissue levels
      of E2 and increased concentrations of 2-methoxy-E2, as implied by this study and
      the previous one, may contribute to the protective effect of daidzein against
      breast and endometrial cancer.

PMID- 16598815
TI  - Biological activities of malvidin, a red wine anthocyanidin.
AB  - Malvidin (mv) has been identified as a potential inhibitor of 3',5'-cyclic
      adenosine monophosphate (cAMP) phosphodiesterases (PDE). This study was to
      investigate if, as a possible consequence of intracellular PDE inhibition, the
      activity of the mitogen-activated protein kinase (MAPK) cascade is affected by mv
      treatment. At a concentration of 5 microM of mv a significant decrease of
      phosphorylated ERK1 and ERK2 (ERK, extracellular regulated kinase) in HT29 cells
      was observed. However, an increase in substance concentration led to a
      substantial recurrence of the phosphorylated enzymes. Cell cycle analysis
      underlined that indeed G(1)-relevant targets are only marginally affected by mv.
      The recurrence of phosphorylated ERK1/2 and the lack of effectiveness on the G(1)
      passage up to 100 microM indicated that the inhibition of cAMP-specific PDEs is
      of minor relevance for the growth-inhibitory properties of mv in HT29 cells. In
      contrast, the release of cells, synchronised in the G(2)/M-phase of the cell
      cycle by nocodazole treatment, was effectively blocked in the presence of 1
      microM mv. These results suggest that mv interferes with cellular targets
      relevant for G(2)/M-progression which have not been identified so far.

PMID- 16598816
TI  - Gene therapy for HIV infection: what does it need to make it work?
AB  - The efficacy of antiviral drug therapy for HIV infection is limited by toxicity
      and viral resistance. Thus, alternative therapies need to be explored. Several
      gene therapeutic strategies for HIV infection have been developed, but in
      clinical testing therapeutically effective levels of the transgene product were
      not achieved. This review focuses on the determinants of therapeutic efficacy and
      discusses the potential and also the limits of current gene therapy approaches
      for HIV infection.

PMID- 16598817
TI  - Interleukin-4-triggered, STAT6-dependent production of a factor that induces
      mouse mast cell apoptosis.
AB  - IL-4 can suppress mast cell development from mouse spleen, bone marrow and
      peritoneal cells by an indirect process that is dependent on the presence of
      macrophages. Mast cells undergo apoptosis when exposed to supernatants collected
      from cultures of IL-4-stimulated peritoneal cells due to the IL-4-induced
      production of an apoptosis-inducing factor in the cultures. This effect of IL-4
      is shown to be dependent on STAT6 signaling, because IL-4 and IL-13 do not
      suppress mast cell development from the spleen and peritoneal cells of STAT6-/-
      mice. Moreover, supernatants from cultures of IL-4- and IL-13-stimulated
      peritoneal cells of STAT6-/- mice do not exhibit apoptosis-inducing activity. We
      confirm, by using deficient mice, neutralizing antibodies and recombinant
      cytokines, that IL-4-induced apoptosis is not related to the well-known apoptosis
      inducing factors Fas, Fas ligand, TNF-alpha, TRAIL, TGF-beta or perforin. These
      results demonstrate a novel mechanism whereby IL-4 and IL-13 can suppress mast
      cell development by inducing the production of an apoptosis-inducing factor from
      macrophages.

PMID- 16598818
TI  - Endocrine disruptors that deplete glutathione levels in APC promote Th2
      polarization in mice leading to the exacerbation of airway inflammation.
AB  - Endocrine-disrupting chemicals (EDC) are ubiquitous in environment and may have
      various undesirable effects on human health. In the present study, we have shown
      that some EDC [benzophenone, p-octylphenol, and tributyltin chloride (TBT)]
      promoted strong Th2 polarization via suppression and augmentation of Th1 and Th2
      development, respectively, from naive CD4+ T cells primed with anti-CD3 and
      splenic antigen-presenting cells (APC). The effect was indicated to be indirect
      via suppression of IL-12 production and augmentation of IL-10 production of APC,
      which are critical for the Th1 and Th2 development, respectively. Such modulation
      of cytokine production by EDC was associated with reduction of intracellular
      glutathione levels in APC. IL-10 deprivation or the addition of N-acetylcysteine,
      which replenishes intracellular glutathione level during priming, cancelled the
      effect of EDC on the promotion of Th2 polarization. Oral administration of TBT,
      which most effectively promoted Th2 polarization in vitro, exacerbated airway
      inflammation in a murine model of allergic asthma with concomitant enhancement of
      Th2-type immunity. Collectively these results suggest that EDC such as
      benzophenone, p-octylphenol, and TBT promote Th2 polarization indirectly via the
      depletion of glutathione in APC and subsequent modulation of IL-10 and IL-12
      production that might result in the exacerbation of allergic diseases.

PMID- 16598820
TI  - Functional CD1a is stabilized by exogenous lipids.
AB  - Self-glycosphingolipids bind to surface CD1 molecules and are readily displaced
      by other CD1 ligands. This capacity to exchange antigens at the cell surface is
      not common to other antigen-presenting molecules and its physiological importance
      is unclear. Here we show that a large pool of cell-surface CD1a, but not CD1b
      molecules, is stabilized by exogenous lipids present in serum. Under serum
      deprivation CD1a molecules are altered and functionally inactive, as they are
      unable to present lipid antigens to T cells. Glycosphingolipids and phospholipids
      bind to, and restore functionality to CD1a without the contribution of newly
      synthesized and recycling CD1a molecules. The dependence of CD1a stability on
      exogenous lipids is not related to its intracellular traffic and rather to its
      antigen-binding pockets. These results indicate a functional dichotomy between
      CD1a and CD1b molecules and provide new information on how the lipid antigenic
      repertoire is immunologically sampled.

PMID- 16598819
TI  - No evidence for dualism in function and receptors: PD-L2/B7-DC is an inhibitory
      regulator of human T cell activation.
AB  - The B7 family member programmed-death-1-ligand 2 (PD-L2/B7-DC) is a ligand for
      programmed-death-receptor 1 (PD-1), a receptor involved in negative regulation of
      T cell activation. Several independent studies have reported that PD-L2, however,
      can also potently costimulate murine T cells via an additional yet unidentified
      receptor. In this study, we evaluated the contribution of PD-L2 to the activation
      of human T cells using a novel system of engineered T cell stimulators that
      expresses membrane-bound anti-CD3 antibodies. Analyzing early activation markers,
      cytokine production and proliferation, we found PD-L2 to consistently inhibit T
      cell activation. PD-L2 inhibition affected CD4+ and CD8+ T cells and was not
      abrogated by costimulation via CD28. Blocking PD-1 reverted the inhibitory effect
      of PD-L2, demonstrating involvement of this pathway. In human T cells, we found
      no evidence for any of the costimulatory effects described for PD-L2 in murine
      systems. In line with our functional data that do not point to stimulatory PD-L2
      ligands, we show that binding of PD-L2-immunoglobulin to activated human T cells
      is abrogated by PD-1 antibodies. Our results demonstrate that PD-L2 negatively
      regulates human T cell activation and thus might be a candidate molecule for
      immunotherapeutic approaches aimed to attenuate pathological immune responses.

PMID- 16598821
TI  - Priming of CD8+ T cell responses following immunization with heat-killed
      Plasmodium sporozoites.
AB  - Protective immune responses against malaria are induced by immunization with
      radiation-attenuated Plasmodium sporozoites. In contrast, non-viable, heat-killed
      sporozoites do not induce protection, emphasizing the requirement for live
      parasites to achieve effective immune responses. Using an experimental system
      with CD8+ T cells from T cell receptor-transgenic mice, we analyzed the primary
      CD8+ T cell responses elicited by heat-killed inactivated sporozoites. We found
      that the numbers of specific CD8+ T cells induced were much lower compared to
      when immunizing with attenuated sporozoites; however, the kinetics of activation
      and the phenotype of these T cells were similar in both groups. Despite their low
      frequency after priming, high numbers of specific CD8+ T cells were observed
      after boosting with a recombinant vaccinia virus. Upon induction of the recall
      response, the same level of protection was observed when either heat-killed or
      attenuated sporozoites were used for priming. We propose that live parasites are
      not critical for the induction of memory T cell populations against the malaria
      liver stages.

PMID- 16598822
TI  - Core concerns of couples living with early stage breast cancer.
AB  - STUDY OBJECTIVES: Although clinicians and scientists have a growing awareness of
      breast cancer as a couple's joint experience, no one has studied the concerns
      couples choose to address with a professional coach to better manage the impact
      of the cancer. The purpose of the current study was to describe illness-related
      concerns couples worked on together with masters-educated professional coaches
      during the first eleven months of the wife's treatment for early stage breast
      cancer. SETTING AND PARTICIPANTS: Intervention sessions were conducted with
      twenty-nine couples in their homes in the Pacific Northwest. DESIGN: Data were
      obtained from single occasion case intensive interviews with couples. MAIN
      RESULTS: Inductive coding of the audiorecorded intervention sessions yielded four
      domains of core concerns: dealing with tension in the relationship; needing to be
      together as a couple; wondering about the children; and managing the threat of
      breast cancer. CONCLUSION: Over half the couples chose to address and do
      something about the stress, tension and dissatisfaction they were feeling in
      their relationship that each attributed to the breast cancer. Future family
      focused cancer care needs to include services that assist couples to address
      these core concerns.

PMID- 16598823
TI  - Skewed expression of natural-killer (NK)-associated antigens on
      lymphoproliferations of large granular lymphocytes (LGL).
AB  - Killer-immunoglobulin-like receptors (KIR) or C-type lectin-like receptors are
      heterogeneously expressed on NK cells and small subsets of T cells and might
      provide a new diagnostic tool for LGL lymphoproliferations (LGLL). We
      investigated the diagnostic impact of these cell surface molecules in T- and NK
      type LGLL. Using three-color flow cytometry we examined the expression patterns
      of KIR (CD158a/b/e/i), CD85j, lectin-like receptors (CD94, CD161, NKG2A/D) and
      natural cytotoxicity receptors (NKp30/44/46) in 13 patients with LGLL (10 T-, 3
      NK-LGLL) and compared them to those of the corresponding lymphocyte subsets in 20
      control subjects. The presence of clonal TCR-gamma rearrangements and of Epstein
      Barr virus- (EBV) DNA were evaluated by PCR. All patients exhibited an altered
      expression of NK-associated markers. KIR were either lacking (6/13) or
      overexpressed (7/13). CD94 expression was significantly higher in all LGLL. NKG2A
      expression was significantly higher in NK-LGLL. Absence or overexpression was
      observed for NKG2A in T-LGLL and CD161 in most T/NK-LGLL. In NK-LGLL expression
      of NKp30 and NKp46 was significantly decreased, whereas CD85j was overexpressed.
      We consistently found a skewed expression pattern of novel NK markers as a
      pathological feature of LGLL. These antigens should be included in the diagnostic
      workup of this rare disease.

PMID- 16598824
TI  - Molecular characterization of polyphosphate (PolyP) operon from Serratia
      marcescens.
AB  - The polyphosphate (polyP) operon was cloned from a genomic library of Serratia
      marcescens KCTC 2172 by Southern hybridization using E. coli ppk gene as a probe.
      The polyP operon was composed of a polyphosphate promoter, polyphosphate kinase
      (ppk) and exopolyphosphatase (ppx). A potential CRP binding site and pho box
      sequence were found in the region upstream of the putative promoter in the
      regulatory region. The ppk gene comprises 2,063 nucleotides and encodes 686 amino
      acids yielding a protein with a molecular mass of 70 kDa. The ppx gene contains
      1611 nucleotides and encodes 536 amino acids with a molecular 58 kDa. An E. coli
      strain transformed with the ppk gene had a 16-fold increased in polyphosphate
      kinase activity, while introduction of the ppx gene produced a 25-fold increase
      in polyphosphatase activity. E. coli strains transformed with ppk and ppx genes
      also displayed increased accumulation of polyphosphate.

PMID- 16598825
TI  - The DNA region of phage BF23 encoding receptor binding protein and receptor
      blocking lipoprotein lacks homology to the corresponding region of closely
      related phage T5.
AB  - Analysis of the DNA region upstream of the BF23 hrs gene revealed a genetic
      organisation similar to that of closely related phage T5. A gene encoding a
      lipoprotein (llp(BF23)) is located directly upstream of the gene encoding the
      receptor binding protein (hrs) but is transcribed in opposite direction. The gene
      is followed by four open reading frames transcribed in the same direction. The
      llp (BF23) gene product does not show similarity to the corresponding T5 Llp(T5)
      protein, however, like Llp(T5) does for FhuA it blocks the BtuB receptor for BF23
      infection. While no similarity between BF23 and T5 was observed for the DNA
      region encoding Llp and the receptor binding protein, the flanking regions were
      highly similar. Based on our results we conclude that a genetic module, the
      receptor-binding/receptor-blocking module, exists in phages BF23 and T5. Due to
      exclusion of homologous recombination within this module, it is hereditary only
      as an intact module: separation of the receptor-binding gene from the receptor
      blocking gene, which apparently results in reduced fitness of the phage due to
      inactivation of progeny phage by active receptor proteins in the outer membranes
      of lysed cells, is thus effectively prevented.

PMID- 16598826
TI  - Co-production of ligninolytic enzymes by Pleurotus pulmonarius on wheat bran
      solid state cultures.
AB  - In this paper, the production of biomass and ligninolytic enzymes by the white
      rot fungus Pleurotus pulmonarius (Fr.) Quelet cultured on wheat bran at high
      initial moisture was evaluated. When the initial moisture was lower than 86%, the
      fungal hyphae penetrated into and bound tightly to the solid-substrate particles.
      When the moisture was equal or higher than 86%, the growth was characterized by
      formation of a large mycelial mass above the substrate (surface growth). In this
      case, the mycelial mass could be easily separated from the residual solid
      substrate and quantified by gravimetric analysis. The fungus produced 0.32 g of
      dry mycelial mass per g of dry substrate after 15 days of cultivation. Analysis
      of the residual substrate showed that growth was mainly due to the consumption of
      soluble proteins and carbohydrates. The condition of high initial moisture
      strongly promoted the expression of laccase (up to 24,000 U per g of substrate or
      78,000 U per g of dry fungal biomass), while the production of manganese
      peroxidase was negatively affected. In fact, manganese peroxidase was maximally
      produced when the initial moisture was 75% (2,000 U per g of substrate). The
      production of other enzymes, such as polysaccharidases and proteases, was not
      significantly affected by the initial moisture.

PMID- 16598827
TI  - Effect of pretreatment of salt, copper and temperature on ultraviolet-B-induced
      antioxidants in diazotrophic cyanobacterium Anabaena doliolum.
AB  - Effect of salt, copper, and temperature pretreatments on the UV-B-induced
      oxidative damage, measured in terms of peroxide and MDA (lipid peroxidation)
      contents, was studied in the diazotrophic cyanobacterium Anabaena doliolum. To
      understand the survival strategy enzymatic (superoxide dismutase, catalase,
      glutathione reductase, and ascorbate peroxidase) and non-enzymatic (glutathione,
      ascorbate, alpha-tocopherol and carotenoid) antioxidants were studied. Among the
      various pretreatments salt was found to decrease and copper and temperature
      pretreatments increased the deleterious effects of UV-B. This study is the first
      to demonstrate that physical stress (high temperature) enhanced the damaging
      effect of UV-B more profoundly than chemical stresses (salt and copper).

PMID- 16598828
TI  - Metal tolerance of yeasts isolated from water, soil and plant environments.
AB  - The tolerance of seventy yeast strains belonging to 15 species, isolated from
      water and soil environments as well as from tree leaves, to four heavy metals-
      copper, zinc, nickel and cadmium were studied. We have found that the
      interspecific and intraspecific variations in metal tolerance among studied
      strains were considerable. The highest interspecific variations were observed
      toward copper and cadmium. The strains of the species Sporobolomyces
      salmonicolor, Cryptococcus albidus, Cystofilobasidium capitatum, Saccharomyces
      cerevisiae, and Candida maltosa belonged to the most sensitive ones. In general
      ascomycetous yeasts were more tolerant to heavy metals than basidiomycetous ones.
      The differences among strains that came from various natural sources were also
      found. The most sensitive yeast population originated from untilled soil whereas
      the most tolerant population was isolated from tree leaves.

PMID- 16598829
TI  - Pyrimidine base supplementation effects curdlan production in Agrobacterium sp.
      ATCC 31749.
AB  - Pyrimidine base supplementation of the culture medium was found to increase
      curdlan production by Agrobacterium sp. ATCC 31749. With sucrose as a carbon
      source, adding uracil or cytosine to the culture medium of strain ATCC 31749
      after 48 h of growth resulted in an elevation of curdlan levels by 1.7-fold or
      1.5-fold, respectively, after 120 h compared to no addition. Supplementation of
      the pyrimidine bases thymine, dihydrouracil or orotic acid had no effect upon
      curdlan production. Biomass production by strain ATCC 31749 after uracil
      supplementation was noted to increase by 3.0-fold after 120 h of growth compared
      to the control cultures. The increase in curdlan production by Agrobacterium sp.
      ATCC 31749 following uracil addition appeared to be related to the observed
      increase in biomass production.

PMID- 16598830
TI  - Bacillus thuringiensis and Bacillus sphaericus biopesticides production.
AB  - The long residual action and toxicity of the chemical insecticides have brought
      about serious environmental problems such as the emergence and spread of
      insecticide resistance in many species of vectors, mammalian toxicity, and
      accumulation of pesticide residues in the food chain. All these problems have
      highlighted the need for alternative biological control agents. Entomo-pathogenic
      Bacillus thuringiensis (Bt) and Bacillus sphaericus (Bs) are two safe biological
      control agents. They have attracted considerable interest as possible
      replacements for the chemical insecticides. Although microbial insecticides based
      on Bt and Bs are available for use, their high cost makes large-scale application
      impracticable in developing countries. This review focuses on the economic
      production of these two microorganisms by submerged fermentation and solid state
      fermentation using agro-industrial by-products and other wastes.

PMID- 16598832
TI  - Isolation and characterization of a biphenyl-utilizing psychrotrophic bacterium,
      Hydrogenophaga taeniospiralis IA3-A, that cometabolize dichlorobiphenyls and
      polychlorinated biphenyl congeners in Aroclor 1221.
AB  - A psychrotrophic bacterium isolated from polychlorinated biphenyls (PCBs)
      contaminated soil grew on biphenyl as sole carbon and energy source, and actively
      cometabolized PCBs at low temperature. Analysis of cellular fatty acids indicate
      that the bacterium is most closely related to Hydrogenophaga taeniospiralis.
      Resting cells incubated with 10 ppm of Aroclor 1221 at 5 or 30 degrees C for 48 h
      removed all mono-, most di-, and several trichlorobiphenyls. At 5 degrees C,
      removal of MCBs (monochlorobiphenyls) was between 63 to 89%, DCBs
      (dichlorobiphenyls) was between 30 to 78%, and TCBs (trichlorobiphenyls) was
      between 30 to 75%. At 30 degrees C, removal of MCBs was 100%, DCBs was between 30
      to 100%, and TCBs was between 27 to 59%. Congeners with two or more ortho
      chlorine were generally resistant to degradation. However, removal of di-ortho
      plus para-substituted congeners at 30 degrees C and not at 5 degrees C, suggest
      that the presence of a para-chlorine enhanced the cometabolism of these congeners
      at 30 degrees C. Furthermore, after 72 h, resting cells removed 68 and 83% of 500
      microM of 2,4'-dichlorobiphenyl (2,4'-DCB) and, 35 and 44% of 500 microM of 2,3
      dichlorobiphenyl (2,3-DCB) at 5 and 30 degrees C, respectively. Analysis of
      metabolites by GC-MS indicates that the cometabolized 2,3-DCB was completely
      recovered as 2,3-chlorobenzoic acid (2,3-CBA), while the cometabolized 2,4'-DCB
      was not completely recovered as chlorobenzoic acid. To our knowledge, it is the
      first strain of Hydrogenophaga taeniospiralis found to degrade an organic
      pollutant, and also the first psychrotrophic strain of a member of the genus
      Hydrogenophaga to grow on biphenyl or cometabolize PCBs at low temperature.
      Results suggest that the bacterium has potential use in the bioremediation of PCB
      contaminated sites in cold regions.

PMID- 16598831
TI  - Inhibition of clinical and environmental Cryptococcus neoformans isolates by two
      Brazilian killer yeasts.
AB  - Two killer yeast strains (HB55 and HB88) capable of inhibiting human pathogenic
      fungi were isolated from leaves of Hibiscus rosa-sinensis in Brazil. These
      isolates were identified by conventional methods and sequencing of the D1/D2
      region of the 26S rDNA as Kodamaea ohmeri. They inhibited all Cryptococcus
      neoformans (vars. neoformans, grubii and gattii) strains tested, including
      reference, clinical and environmental isolates. The killer phenotype was not
      cured by thermal treatment.

PMID- 16598833
TI  - A qualitative study of factors affecting chemotherapy use in older women with
      breast cancer: barriers, promoters, and implications for intervention.
AB  - STUDY OBJECTIVE: The incidence of breast cancer increases with advancing age and
      yet women 65 and older (hereinafter referred to as 'older' women) do not always
      receive the most intensive treatments, such as adjuvant chemotherapy. The causes
      of underutilization of chemotherapy in this age group are poorly delineated. The
      purpose of the study was to explore older breast cancer patients' attitudes
      towards chemotherapy and factors that influenced their decisions to use or not
      use this treatment modality. DESIGN: Qualitative methods were used to conduct
      race/ethnicity-specific focus groups. A thematic analysis was performed using
      NVIVO. SETTING AND PARTICIPANTS: Drawn from the Washington, DC area, participants
      were 34 ethnically diverse older breast cancer survivors (18 Caucasians, 10
      African-Americans, and 6 Latinas). Focus groups were conducted in a local church;
      a senior center, and the Lombardi Cancer Center. MAIN RESULTS: Results showed
      that many women felt they had no 'choice' and did what the doctor told them to
      do. For those who reported participation in the decision, time spent exchanging
      information with the woman's physician and the inclusion of family members
      promoted perceptions of optimum decision-making leading to the use of
      chemotherapy. Two barriers to using chemotherapy were negative expectations about
      side effects and lack of information specific to the woman's individuals'
      circumstances. Women of color reported less physician communication and
      information, in part due to language difficulties and perceived bias; these
      factors acted as barriers to chemotherapy. CONCLUSION: Physicians could provide
      specific and limited information to patients and family members to promote
      realistic expectations and optimum decisions about chemotherapy, given the risks
      involved in this treatment modality. Interventions should be developed and tested
      to enhance communication that is sensitive to older women's culture, family
      structure, illness experiences, preferences, and expectations.

PMID- 16598834
TI  - Generation of the BCR/ABL fusion gene in a Philadelphia chromosome-negative
      chronic myeloid leukaemia: insertion of 5.6 Mb of 9q34 into the BCR region of
      chromosome 22.
AB  - This report describes a chronic myelogenous leukaemia patient with an apparently
      normal bone marrow karyotype but BCR/ABL fusion-gene-positive. Commercial FISH
      probes showed an atypical pattern and the BCR/ABL fusion transcript was detected
      by RT-PCR, but not the reciprocal ABL/BCR. Consecutive FISH assays clarified the
      mechanism of the masked Ph. The ABL gene and the following 5.6-5.7 Mb of 9q are
      inserted into the BCR region of chromosome 22. There is no transference of 22q
      material to chromosome 9 or to any other chromosomes. Clinical features and
      evolution of the patient are similar to those cases with classic Ph chromosome.

PMID- 16598835
TI  - Interview of patients by pharmacists contributes significantly to the
      identification of drug-related problems (DRPs).
AB  - PURPOSE: To investigate whether pharmacist interviews of hospitalised patients
      about their medication would result in identification of more drug-related
      problems (DRPs) than those found by usual care procedures and further to
      characterise the DRPs revealed at the interviews. METHODS: Patients from five
      internal medicine and two rheumatology departments in four hospitals in Norway
      were prospectively included in the study. Clinical pharmacists assessed DRPs by
      reviewing medical records and by participating in multidisciplinary team
      discussions. Drugs used, medical history, laboratory data and
      clinical/pharmacological risk factors were recorded (usual care procedure). A
      proportion of patients were randomly selected for interview with pharmacists. A
      quality team assessed the clinical significance of the DRPs. RESULTS: Seven
      hundred and twenty seven patients were included. Significantly more DRPs were
      found in the interview group (96 patients), an average of 4.4 DRPs per patient as
      compared to 2.4 DRPs in the non-interview group (631 patients) (p < 0.01). Of a
      total of 431 DRPs recorded in the interview group, 168 DRPs (39.9%) were
      disclosed through interviews. 'Need for additional drug', 'medical chart error',
      'patient adherence' and 'need for patient education' were significantly more
      often recorded in this group. The quality team assessed 63% of the DRPs revealed
      in the interviews to be of major clinical significance. CONCLUSION: Significantly
      more DRPs were identified among the patients who were interviewed compared to
      those patients having only usual care examination. A high proportion of the DRPs
      identified in the interviews were of major clinical significance. The clinical
      pharmacists, with their way of interviewing, seem to fill a gap, ensuring that
      significant DRPs do not escape detection.

PMID- 16598836
TI  - Allele and genotype frequencies of polymorphic FMO3 gene in two genetically
      distinct populations.
AB  - The aims of this study were to analyze flavin-containing monooxygenase 3 (FMO3)
      polymorphisms and allele and genotype frequencies in 256 Han Chinese and 50
      African-American individuals, to compare the allele and genotype frequencies of
      these populations with those of other world populations. For Han Chinese,
      genotyping of three common single nucleotide polymorphisms, E158K, V257M and
      E308G was performed by polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP). For African-Americans, genotyping of all coding exons
      was performed by modified PCR-single strand conformational polymorphism (SSCP).
      Evolutionary rates of FMO3 were estimated computationally. We found that there
      were significant differences in allele and genotype frequencies among Han
      Chinese, African-Americans and other world populations. In Han Chinese, the minor
      allele frequencies (MAFs) were 0.229 (E158K), 0.203 (V257M) and 0.148 (E308G),
      respectively. In African-Americans, MAFs were 0.48 (E158K), 0.05 (V257M) and 0
      (E308G), respectively. There was rapid evolution during the divergence of primate
      FMO3. This is the first report comparing FMO alleles and genotypes between Han
      Chinese and African-Americans. A Han Chinese population database has been
      established for three gene polymorphisms. The data presented here justify further
      pharmacogenetic studies for potentially optimizing recommended drug dosages and
      evaluating relationships with disease processes.

PMID- 16598837
TI  - Analysis of CC chemokine receptor 5 and 2 polymorphisms and renal transplant
      survival.
AB  - Chronic rejection is an immune process leading to graft failure. By regulating
      the trafficking of leukocytes, chemokines and chemokine receptors are thought to
      be one of the reasons causing acute renal rejection (ARE), which increases the
      possibility of chronic rejection and organ destruction. This study was designed
      to investigate, in the Turkish population, an association of chemokine receptor
      genetic variants, CCR2V641, CCR5-59029-A/G, CCR5-Delta32 and acute renal
      rejection after renal transplant surgery. We carried out our study in 85 Turkish
      renal transplant patients (45 men, 40 women; mean age 39 +/- 2 years) by
      polymerase chain reaction (PCR) and restriction fragment length polymorphism
      (RFLP) techniques. We found no significant difference in the incidence of
      rejection among patients possessing or lacking CCR5-Delta32. For the groups with
      and without acute renal rejection, we found a significant difference between the
      groups in A and G allele distribution in both CCR2V641and CCR559029 gene variants
      (p = 0.003 and p = 0.003, respectively). According to our findings, the risk of
      acute rejection in renal transplantation may be associated with genetic variation
      in the chemokine receptor genes CCR5-59029 and CCR2V641 in Turkey, and studies on
      these gene polymorphisms could be an ideal target for future interventions
      intended to prevent renal transplant loss.

PMID- 16598838
TI  - Custody. Parental termination upheld for HIV-positive mom.

PMID- 16598839
TI  - Custody. HIV-positive mother loses parental rights of infant.

PMID- 16598840
TI  - Prison. Officers' records opened to determine HIV-bias.

PMID- 16598841
TI  - Beta-carboline derivatives: novel photosensitizers that intercalate into DNA to
      cause direct DNA damage in photodynamic therapy.
AB  - Novel 1,3,9-trisubstituted beta-carboline derivatives were found to exhibit DNA
      photocleavage properties under visible light irradiation in a cell-free system,
      which could be reduced by antioxidant vitamin E. Their photo-cytotoxicity to
      human tumor cell line HeLa was confirmed, in which apoptosis only contributed a
      small part to the cell death, and necrosis was the dominating outcome of HeLa
      cells in photodynamic therapy (PDT) using beta-carboline derivatives. Different
      from other clinical PDT drugs, beta-carboline derivatives were demonstrated to be
      able to distribute in the nucleus and intercalate into DNA, and consequently
      cause direct DNA damage by photochemical reaction products in PDT, which was
      proved by the distinct DNA tails in the comet assay and the considerable amount
      of DNA damaged cells quantified by flow cytometry. This mechanism could be the
      explanation for the delay of cell proliferation at DNA synthesis and mitosis.

PMID- 16598842
TI  - Chemical modification of siRNAs to improve serum stability without loss of
      efficacy.
AB  - Development of RNA interference as a novel class of therapeutics requires
      improved pharmacokinetic properties of short interfering RNA (siRNA). To confer
      enhanced serum stability to Sur10058, a hyperfunctional siRNA which targets
      survivin mRNA, a systematic modification at the 2'-sugar position and
      phosphodiester linkage was introduced into Sur10058. End modification of three
      terminal nucleotides by 2'-OMe and phosphorothioate substitutions resulted in a
      modest increase in serum stability, with 3' end modification being more
      effective. Alternating modification by 2'-OMe substitution significantly
      stabilized Sur10058, whereas phosphorothioate modification was only marginally
      effective. Through various combinations of 2'-OMe, 2'-F and phosphorothioate
      modifications that were directed mainly at pyrimidine nucleotides, we have
      identified several remarkably stable as well as efficient forms of Sur10058.
      Thus, our results provide an effective means to stabilize siRNA in human serum
      without compromising the knockdown efficiency. This advancement will prove useful
      for augmenting the in vivo potency of RNA interference.

PMID- 16598843
TI  - Split and whole liver transplantation outcomes: a comparative cohort study.
AB  - A specific split liver transplantation (SLT) program has been pursued in the
      North Italian Transplant program (NITp) since November 1997. After 5 yr, 1,449
      liver transplants were performed in 7 transplant centers, using 1,304 cadaveric
      donors. Whole liver transplantation (WLT) and SLT were performed in 1,126 and 323
      cases, respectively. SLTs were performed in situ as 147 left lateral segments
      (LLS), 154 right trisegment liver (RTL) grafts, and 22 modified split livers
      (MSL), used for couples of adult recipients. After a median posttransplant follow
      up of 22 months, SLTs achieved a 3-yr patient and graft survival not
      significantly different from the entire series of transplants (79.4 and 72.2% vs.
      80.6 and 74.9%, respectively). Recipients receiving a WLT or a LLS showed
      significantly better outcomes than patients receiving RTL and MSL (P < 0.03 for
      patients and P < 0.04 for graft survival). At the multivariate analysis, donor
      age of >60 yr, RTL transplant, <50 annual transplants volume, urgent
      transplantation (United Network for Organ Sharing (UNOS) status I and IIA),
      ischemia time of >7 hours, and retransplantation were factors independently
      related to graft failure and to significantly worst patient survival. Right
      grafts procured from RTL and either split procured as MSL had a similar outcome
      of marginal whole livers. In conclusion, in 5 yr, the increased number of
      pediatric transplants due to split liver donation reduced to 3% the in-list
      children mortality, and a decrease in the adult patient dropout rate from 27.2 to
      16.2% was observed. Such results justify a more widespread adoption of SLT
      protocols, organizational difficulties not being a limit for the application of
      such technique.

PMID- 16598844
TI  - Cerebellar ataxia and snoring.

PMID- 16598845
TI  - Nicotine prevents the apoptosis induced by menadione in human lung cancer cells.
AB  - Approximately 50% of long-term cigarette smokers die prematurely from the adverse
      effects of smoking, including on lung cancer and other illnesses. Nicotine is a
      main component in tobacco and has been implicated as a potential factor in the
      pathogenesis of human lung cancer. However, the mechanism of nicotine action in
      the development of lung cancer remains largely unknown. In the present study, we
      designed a nicotine-apoptosis system, by pre-treatment of nicotine making lung
      cancer cell A549 to be in a physiological nicotine environment, and observed that
      nicotine promoted cell proliferation and prevented the menadione-induced
      apoptosis, and exerts its role of anti-apoptosis by shift of apoptotic stage
      induced by menadione from late apoptotic stage to early apoptotic stage, in which
      NF-kappaB was up-regulated. Interference analysis of NF-kappaB in A549 cells
      showed that knock down of NF-kappaB resulted in apoptosis promotion and
      counteracted the protective effect of nicotine. The findings suggest that
      nicotine has potential effect in lung cancer genesis, especially in patients with
      undetectable early tumor development and development of specific NF-kappaB
      inhibitors would represent a potentially exciting new pharmacotherapy for tobacco
      related lung cancer.

PMID- 16598846
TI  - Hypobaric hypoxia affects endogenous levels of alpha-keto acids in murine heart
      ventricles.
AB  - Alpha-keto acids have recently been identified as potent regulators of cellular
      adaptations to hypoxia. Their actual intracellular concentrations under such
      conditions are unknown. Here, we determined concentrations of alpha-ketobutyrate,
      alpha-ketoglutarate, alpha-ketoisocaproate, alpha-ketoisovalerate, alpha-keto
      beta-methylvalerate, phenylpyruvate, and pyruvate by a recently developed ultra
      sensitive fluorescence HPLC method in ventricular myocardium of mice exposed to
      hypobaric hypoxia for up to 3 weeks. We observed characteristic alterations of
      cardiac alpha-keto acid concentrations that are specific for individual alpha
      keto acids, show significant side differences (right versus left ventricles), and
      are suited to trigger some of the cardiac metabolic and structural adaptations to
      chronic hypoxia.

PMID- 16598847
TI  - Quality takes center stage in transplantation.

PMID- 16598849
TI  - Increasing the liver donor pool through donation after cardiac death.

PMID- 16598848
TI  - Different COX-independent effects of the COX-2 inhibitors etoricoxib and
      lumiracoxib.
AB  - Etoricoxib and lumiracoxib are both highly selective COX-2 inhibitors. This drug
      class has recently been linked to severe side effects in particular within the
      cardiovascular system. The underlying signal transduction pathway is not
      clarified at the moment but different COX-independent mechanisms might contribute
      to wanted and unwanted effects of these drugs. Here, we investigated COX-2
      independent effects of etoricoxib and lumiracoxib. Both inhibited the activation
      of the transcription factor NF-kappaB, but had no effects on activation of the AP
      1 subunits c-jun and c-fos. On the other hand, activation of the transcription
      factor CREB was dose-dependently inhibited only by etoricoxib. Together with NF
      kappaB-inhibition this might contribute to the reduced protein expression of the
      pro-inflammatory proteins COX-2 and iNOS. In contrast, lumiracoxib did not
      influence CREB activation and showed no effect on iNOS and COX-2 protein
      expression. In conclusion, we showed that etoricoxib and lumiracoxib have
      different COX-independent mechanisms which may be of clinical relevance.

PMID- 16598850
TI  - Predicting posttransplantation infection risk with gene polymorphisms.

PMID- 16598851
TI  - Oral glucose ingestion attenuates exercise-induced activation of 5'-AMP-activated
      protein kinase in human skeletal muscle.
AB  - 5'-AMP-activated protein kinase (AMPK) has been suggested to be a 'metabolic
      master switch' regulating various aspects of muscle glucose and fat metabolism.
      In isolated rat skeletal muscle, glucose suppresses the activity of AMPK and in
      human muscle glycogen loading decreases exercise-induced AMPK activation. We
      hypothesized that oral glucose ingestion during exercise would attenuate muscle
      AMPK activation. Nine male subjects performed two bouts of one-legged knee
      extensor exercise at 60% of maximal workload. The subjects were randomly assigned
      to either consume a glucose containing drink or a placebo drink during the two
      trials. Muscle biopsies were taken from the vastus lateralis before and after 2 h
      of exercise. Plasma glucose was higher (6.0 +/- 0.2 vs. 4.9 +/- 0.1 mmol L-1, P <
      0.001), whereas glycerol (44.8 +/- 7.8 vs. 165.7 +/- 22.3 micromol L-1), and free
      fatty acid (169.3 +/- 9.5 vs. 1161 +/- 144.9 micromol L-1) concentrations were
      lower during the glucose compared to the placebo trial (both P < 0.001).
      Calculated fat oxidation was lower during the glucose trial (0.17 +/- 0.02 vs.
      0.25 +/- 0.03 g min-1, P < 0.001). Activation of alpha2-AMPK was attenuated in
      the glucose trial compared to the placebo trial (0.24 +/- 0.07 vs. 0.46 +/- 0.14
      pmol mg-1 min-1, P = 0.03), whereas the alpha1-AMPK activity was not different
      between trials or affected by exercise. AMPK and the downstream target of AMPK,
      acetyl-CoA carboxylase-beta, were phosphorylated as a response to exercise, but
      neither was significantly different between the two trials. We conclude that oral
      glucose ingestion attenuates the exercise-induced activation of alpha2-AMPK,
      bringing further support for a fuel-sensing role of AMPK in skeletal muscle.

PMID- 16598852
TI  - In vitro panning of a targeting peptide to hepatocarcinoma from a phage display
      peptide library.
AB  - Phage display technology has been used as a powerful tool in the discovery of
      ligands specific to receptor(s) on the surface of a cancer cell and could also
      impact clinical issues including functional diagnosis and cell-specific drug
      delivery. After three rounds of in vitro panning and two rounds of reverse
      absorption, a group of phages capable of addressing BEL-7402 enormously were
      obtained for further analysis. Through a cell-based ELISA, immunofluorescence,
      FACS, and in vivo binding study, WP05 (sequence TACHQHVRMVRP) was demonstrated to
      be the most effective peptide in targeting four kinds of liver cancer cell lines
      (BEL-7402, BEL-7404, SMMC-7721, and HepG2), but not the normal liver cell line HL
      7702. In conclusion, the peptide WP05 which was screened by in vitro phage
      display technology was proved to be a targeting peptide to several common
      hepatocellular carcinoma cell lines.

PMID- 16598854
TI  - News from neurology.

PMID- 16598853
TI  - Accelerated intervertebral disc degeneration in scoliosis versus physiological
      ageing develops against a background of enhanced anabolic gene expression.
AB  - Molecular consequences of long-term deformation and altered mechanical loading of
      intervertebral disc (IVD) tissue in scoliosis have yet to be elucidated. We
      hypothesized that histological disc degeneration is faster in scoliosis than in
      normal ageing and that this is reflected by an altered gene expression profile. A
      semiquantitative histodegeneration score (HDS) revealed significantly enhanced
      degeneration in scoliosis (HDS 5.3) versus age-matched control IVDs (HDS 2.25; p
      = 0.001). Gene expression analysis by cDNA array and RT-PCR demonstrated higher
      mRNA levels for extracellular-matrix molecules like aggrecan, biglycan, decorin,
      lumican, chondromodulin, and COL2A1 in scoliotic discs versus normal discs of
      identical degeneration score. No differences were evident for catabolic molecules
      like MMP3, MMP13, MMP17, and TIMP1. In sum, morphologic disc degeneration was
      accelerated by about 2 decades in scoliosis versus physiological ageing and
      developed against a background of stronger anabolic matrix metabolism at younger
      age or in response to the altered mechanical environment of the tissue.

PMID- 16598855
TI  - Active site mutant acetylcholinesterase interactions with 2-PAM, HI-6, and DDVP.
AB  - We used mouse recombinant wild-type acetylcholinesterase (AChE; EC 3.1.1.7),
      butyrylcholinesterase (BChE; EC 3.1.1.8), and AChE mutants with mutations (Y337A,
      F295L, F297I, Y72N, Y124Q, and W286A) that resemble residues found at
      structurally equivalent positions in BChE, to find the basis for divergence
      between AChE and BChE in following reactions: reversible inhibition by two
      oximes, progressive inhibition by the organophosphorus compound DDVP, and oxime
      assisted reactivation of the phosphorylated enzymes. The inhibition enzyme-oxime
      dissociation constants of AChE w.t. were 150 and 46 microM, of BChE 340 and 27
      microM for 2-PAM and HI-6, respectively. Introduced mutations lowered oxime
      binding affinities for both oximes. DDVP progressively inhibited cholinesterases
      yielding symmetrical dimethylphosphorylated enzyme conjugates at rates between
      104 and 105/min/M. A high extent of oxime-assisted reactivation of all conjugates
      was achieved, but rates by both oximes were up to 10 times slower for
      phosphorylated mutants than for AChE w.t.

PMID- 16598856
TI  - Serum-induced expression of metallothionein isoforms in K-562 cells.
AB  - The metallothionein (MT) expression was studied in the hematopoietic precursor
      cell line K-562, after serum deprivation and reconstitution of the cells in
      medium with 10% (v/v) FCS. Serum deprivation for 72 h markedly downregulated the
      MT mRNA expression, only the isoforms most abundant in normal K-562 cells were
      clearly detectable. Within 1-1.5 h after serum supplementation however, a
      definite induction of MT mRNA was noticed, and all isoforms were induced. Forty
      eight hours after serum stimulation, the MT mRNA expression of all isoforms
      decreased again. Also MT protein levels increased twofold 24 h after serum
      stimulation. These results suggest that MT has a function in the re-entry of
      resting cells into the cell cycle, this function however could not be assigned to
      a specific MT isoform. The induction of MT after serum stimulation was
      independent of protein synthesis, but dependent on phosphorylation.

PMID- 16598857
TI  - Carbon monoxide protects PC12 cells from peroxynitrite-induced apoptotic death by
      preventing the depolarization of mitochondrial transmembrane potential.
AB  - Heme oxygenase-1 (HO-1), the rate-limiting enzyme in catalyzing heme degradation
      into biliverdin, free iron, and carbon monoxide (CO), serves as a protective
      enzyme against oxidative and nitrosative stresses. In the present study, we
      investigated the cytoprotective effects of HO-1 upregulation and its product CO
      against the peroxynitrite-induced PC12 cell death. PC12 cells treated with 3
      morphoinosydonimine (SIN-1), a generator of peroxynitrite (ONOO-), underwent
      apoptotic cell death as evidenced by dissipation of mitochondrial transmembrane
      potential (DeltaPsim), release of mitochondrial cytochrome c into cytoplasm,
      cleavage of poly(ADP-ribose)polymerase and fragmentation of internucleosomal DNA.
      Pretreatment of PC12 cells with a low non-toxic concentration of SIN-1 (0.5 mM)
      induced HO-1 expression and abrogated the cell death caused by subsequent
      challenge with high dose SIN-1 (2.5 mM). Furthermore, pretreatment of PC12 cells
      with SnCl2, a potent inducer of HO-1 expression, increased endogenous production
      of CO (HO activity) and rescued the PC12 cells from peroxynitrite-induced
      apoptosis. The cytoprotective effect of SnCl2 was abolished when the HO activity
      was inhibited by zinc protoporphyrin IX (ZnPP IX). PC12 cells treated directly
      with the CO-releasing molecule, tricarbonyldichlororuthenium (II) dimer
      ([Ru(CO)3Cl2]2) became tolerant to the depolarization of DeltaPsim and apoptosis
      induced by high dose peroxynitrite. Taken together, these data demonstrate that
      the adaptive protection against peroxynitrite-induced apoptotic death in PC12
      cells is mediated by CO formed as a consequence of HO-1 induction.

PMID- 16598858
TI  - Mitochondrial cytochrome c reacts with nitric oxide via S-nitrosation.
AB  - The present study demonstrates that mitochondrial cytochrome c reacts with the
      thiol-reacting agent N-ethylmaleimide (NEM) to produce a one NEM-adducted
      cytochrome c. Mitochondrial cytochrome c also reacts with 5,5'-dithio-bis-(2
      nitrobenzoic acid) and 1-chloro-2,4-dinitrobenzene in a manner prevented with NEM
      or iodoacetic acid (IAA). NEM-treated cytochrome c has lower reducibility and
      lower function to support mitochondrial oxygen consumption. These findings
      suggest that mitochondrial cytochrome c contains a reactive thiol that is
      involved in the functions of cytochrome c for mitochondria. Nitric oxide reacts
      with the cytochrome c thiol to generate S-nitroso (SNO)-cytochrome c in a manner
      prevented with NEM or IAA. SNO-cytochrome c has lower reducibility and function
      to support mitochondrial oxygen consumption, similar to NEM-treated cytochrome c.

PMID- 16598859
TI  - Identification of a novel inactivating R465Q mutation of the calcium-sensing
      receptor.
AB  - In this study, we describe a 52-year-old woman, who was diagnosed with familial
      benign hypocalciuric hypercalcemia (FBHH), a condition characterized by
      hypercalcemia, low urinary calcium excretion, and normal parathyroid hormone PTH
      levels, resulting from inactivating mutations of the calcium-sensing receptor
      (CaSR). In order to identify and characterize the underlying mutation in the CASR
      gene, direct sequence analysis of CASR exons 2-7 was performed, and functional
      activity was examined by transient transfection of human embryonic kidney (HEK
      293) cells with wild-type and mutant CaSRs, followed by intracellular calcium
      measurement using fluorometry, and Western blot analysis. Sequence analysis
      demonstrated, in addition to the already described A986S polymorphism, a novel
      heterozygous G--> A substitution in CASR exon 5 that causes an arginine to
      glutamine substitution at codon 465 (R465Q). Functional analysis showed a
      rightward shift of the dose-response curve with a significant increase of the
      EC50 from 5.4 mM of the CaSR carrying the A986S polymorphism alone to 11.3 mM of
      the CaSR carrying the R465Q mutation in the presence of the A986S polymorphism.
      Western blot analysis of membrane protein revealed an even higher expression
      level of the R465Q mutant protein compared to wild-type CaSR. In conclusion, we
      identified a novel heterozygous loss-of-function R465Q mutation of the CASR gene,
      which is characterized by a blunted response to calcium stimulation, thereby
      causing FBHH.

PMID- 16598860
TI  - Signaling pathways involved in airway disease. An animal model breathes fresh air
      on a complex disorder.

PMID- 16598861
TI  - The role of assisted hatching in in vitro fertilization: a review of the
      literature. A committee opinion.

PMID- 16598862
TI  - [Long term domiciliary mechanical ventilation in patients with neuromuscular
      disease (indications, establishment and follow up)].
AB  - Neuromuscular diseases represent a heterogeneous group of pathologies which
      common feature is the development of a restrictive ventilatory failure.
      BACKGROUND: Respiratory insufficiency of neuromuscular origin manifests itself by
      functional symptoms that must be carefully searched for in the history, such as
      headaches, sleep disorders, or dyspnoea of effort, sometimes very mild, or in
      severe cases associated with orthopnoea. Follow up should be multi-disciplinary.
      On the respiratory level regular measurement of blood gases, vital capacity,
      maximum inspiratory and expiratory pressures as well as sleep studies, will
      detect the criteria for mechanical ventilation (hypercarbia > 45 mm Hg, nocturnal
      desaturation < 88%, vital capacity < 60%, PImax < 60 cm H2O). STATE OF THE ART:
      The establishment of mechanical ventilation is a major decision for patients with
      neuromuscular disease because of the important physical, psychological, social
      and sometimes financial consequences. The patients and their family must be
      instructed precisely in order to obtain the best possible observation and
      compliance. The establishment requires a stay in hospital of several days to
      optimise the choice of ventilator, its settings, and connections. The link with
      the organisation managing the domiciliary ventilation is fundamental in ensuring
      follow up after discharge from hospital. Techniques of cough assistance must be
      taught to each neuromuscular patient requiring mechanical ventilation.
      CONCLUSION: Ventilation of neuromuscular patients requires careful evaluation of
      the indications and rigorous follow up by a multidisciplinary team with wide
      experience of this type of disease.

PMID- 16598863
TI  - [Pneumomediastinum complicating the anti-synthetase syndrome].
AB  - INTRODUCTION: Pneumomediastinum is a rare but classical complication of
      dermatomyositis. Its development is a serious matter and necessitates prompt
      recourse to aggressive treatment with corticosteroids combined with immuno
      suppressants or intravenous human immunoglobulin. CASE REPORT: We report the case
      of a 63 year old woman presenting with pulmonary infiltration, in the presence of
      dermatomyositis, as a clinical manifestation of the anti-synthetase syndrome. The
      progress was rapidly unfavourable with pneumomediastinum and acute respiratory
      distress despite initial treatment with corticosteroids followed by human
      immunoglobulin and immunosuppressants. CONCLUSION: The identification of
      cutaneous or muscular signs in the initial investigation of a pulmonary
      infiltrate should lead to a search for anti-synthetase antibodies in order to
      determine the optimal clinical management as quickly as possible.

PMID- 16598864
TI  - [Mediastinal localisation of a thoracic duct lymphocele--account of a surgical
      case].
AB  - INTRODUCTION: Lymphocele of the thoracic duct is a rare pathological entity
      occurring as a consequence of deterioration and cystic dilation wall of this
      vessel. It may be of congenital or degenerative origin. OBSERVATION: We report
      the case of a 47 year old patient, operated on for a symptomatic cyst localised
      by CT scan to the inferoposterior mediastinum. At postero-lateral thoracotomy it
      was identified as a lymphocele and completely resected. Chemical analysis of the
      liquid and histopathology study of the cystic wall confirmed the diagnosis. The
      patient's post operative course was uneventful. CONCLUSION: This case
      demonstrates the clinical characteristics of this entity and describes diagnostic
      techniques and surgical management.

PMID- 16598865
TI  - [Pulmonary myofibroblastoma: the role of primary surgery].
AB  - INTRODUCTION: Myofibroblastic tumours or pulmonary pseudotumours are rare and,
      though benign, they may become invasive and recur after excision. CASE REPORT: We
      report the case of a child aged 14, presenting with mild haemoptysis, who had a
      solitary nodule at the base of the left lung. CT scanning suggested a
      hypervascular tumour. Fibreoptic bronchoscopy was normal and it was not possible
      to perform percutaneous biopsy on account of its proximal situation. A lobectomy
      was performed via a postero-lateral thoracotomy with a successful outcome.
      Histological examination revealed a myofibroblastic tumour. CONCLUSION: Recourse
      to primary surgery is essential to confirm the diagnosis of a myofibroblastic
      pulmonary tumour. Complete resection is the only guarantee to prevent recurrence.

PMID- 16598866
TI  - [Expert conference: peri-operative smoking].

PMID- 16598867
TI  - Fight or flinch?

PMID- 16598868
TI  - Report from the 45th Interscience Conference on Antimicrobial Agents and
      Chemotherapy.

PMID- 16598869
TI  - Sees cover art birds as unhealthy.

PMID- 16598870
TI  - The splitting headache. Prehospital assessment and treatment of acute head pain.

PMID- 16598871
TI  - Targeting cardiovascular complications.

PMID- 16598872
TI  - Thalidomide gives food for thought in multiple myeloma.

PMID- 16598873
TI  - Inflammatory response predicts survival in renal cancer.

PMID- 16598874
TI  - Patients with blood clots should be screened.

PMID- 16598875
TI  - X marks the spot in basal-like breast cancer.

PMID- 16598876
TI  - Less-frequent erythropoietin for cancer-associated anaemia.

PMID- 16598877
TI  - New drug increases survival in stomach cancer.

PMID- 16598878
TI  - Gene-expression profiles predict secondary leukaemia risk.

PMID- 16598879
TI  - High meat consumption linked to gastric-cancer risk.

PMID- 16598880
TI  - Xaliproden lessens oxaliplatin-mediated neuropathy.

PMID- 16598881
TI  - Early chemotherapy for patients with mesothelioma.

PMID- 16598882
TI  - Autoimmunity aids survival in melanoma.

PMID- 16598883
TI  - Localised prostate cancer: treatment versus surveillance?

PMID- 16598884
TI  - Combined therapy improves survival in oesophageal cancer.

PMID- 16598885
TI  - HAART and CHOP improve survival in AIDS-related lymphoma.

PMID- 16598886
TI  - Virus linked with prostate cancer.

PMID- 16598887
TI  - Sentinel-node mapping for staging of colorectal cancer.

PMID- 16598888
TI  - New findings for hormone-resistant prostate cancer.

PMID- 16598889
TI  - Morbidity after major pulmonary resection in lung cancer.

PMID- 16598891
TI  - Gestational diabetes.

PMID- 16598892
TI  - Body Positive resource directory. Where can I go? A guide to HIV services in New
      York City.

PMID- 16598890
TI  - Carcinogenicity of carbon black, titanium dioxide, and talc.

PMID- 16598894
TI  - Testing your diagnostic skills. Case no. 1: epithelial dysplasia.

PMID- 16598893
TI  - House tackles national exam and access-to-care initiatives.

PMID- 16598895
TI  - [Longitudinal MRI findings of glucose transporter I deficiency syndrome (Glut
      1DS) in a Japanese patient - longitudinal investigation of multifocal T2
      prolonged subcortical lesions, Case Report].

PMID- 16598896
TI  - Letter to the editor: analysis of thermo-mechanical stress in cryopreservation.

PMID- 16598898
TI  - [Impact of obesity in contemporary cardiology].
AB  - Available evidence clearly indicates a rapid progression in the prevalence of
      obesity worldwide. As a consequence, there has also been a marked increase in the
      prevalence of type 2 diabetes all over the world and this chronic metabolic
      disease is now considered as a coronary heart disease risk equivalent. However,
      even in the absence of the hyperglycaemic state which characterizes type 2
      diabetic patients, non diabetic individuals with a specific form of obesity,
      named abdominal obesity, often show clustering metabolic abnormalities which
      include high triglyceride levels, increased apolipoprotein B, small dense low
      dendity lipoproteins and decreased high density lipoproteins-cholesterol levels,
      a hyperinsulinemic-insulin resistant state, alterations in coagulation factors as
      well as an inflammatory profile. This agglomeration of abnormalities has been
      referred to as the metabolic syndrome which can be identified by the presence of
      three of the five following variables: abdominal obesity, elevated triglyceride
      concentrations, low HDL-cholesterol levels, increased blood pressure and elevated
      fasting glucose. Post-mortem analyses of coronary arteries have indicated that
      obesity (associated with a high accumulation of abdominal fat measured at
      autopsy) was predictive of earlier and greater extent of large vessels
      atherosclerosis as well as increase of coronary fatty streaks. Metabolic syndrome
      linked to abdominal obesity is also predictive of recurrent coronary events both
      in post-myocardial infarction patients and among coronary artery disease men who
      underwent a revascularization procedures. It is suggested that until the epidemic
      progression of obesity is stopped and obesity prevented or at least properly
      managed, cardiologists will be confronted to an evolving contribution of risk
      factors where smoking, hypercholesterolemia and hypertension may be relatively
      less prevalent but at the expense of a much greater contribution of abdominal
      obesity and related features of the metabolic syndrome.

PMID- 16598897
TI  - [Effect of propranolol on new daily persistent headache].

PMID- 16598899
TI  - [Adipocytokins, obesity and development of type 2 diabetes].
AB  - Normal metabolic balance is maintained by a complex homeostatic system involving
      multiple tissues and organs. Acquired or inherited defects associated to
      environmental factors in any part of this system can lead to metabolic disorders
      such as the syndrome X which is presently a frequent syndrome in industrialized
      countries. It is characterized by a cluster of risk factors of atherosclerosis
      including insulin resistance, hyperinsulinemia, impaired glucose tolerance or
      type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its
      pathophysiology is likely to involve insulin resistance at the level of both
      skeletal muscle and visceral adipose tissue and altered fluxes of metabolic
      substrates between these tissues that in turn impair liver metabolism.
      Therapeutic intervention favours at present diet and exercise prescriptions. In
      addition, if necessary, specific treatment of the metabolic disorders is
      required. In the treatment of insulin resistance, new promising drugs are likely
      to be used in the next future. In this regard, adipose tissue, once thought to
      function primarily as a passive depot for the storage of excess lipid, is now
      understood to play a much more active role in metabolic regulation, secreting a
      variety of metabolic hormones and actively functioning to prevent deleterious
      lipid accumulation in other tissues and to modulate the insulin resistance. Here,
      we review new advances in our understanding of mechanisms leading to insulin
      resistance and type 2 diabetes from the perspective of the role and interactions
      of recently identified adipocyte-specific chemical messengers, the
      adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6,
      and resistin.

PMID- 16598900
TI  - [Contribution of free fatty acids to impairment of insulin secretion and action.
      mechanism of beta-cell lipotoxicity].
AB  - Type 2 diabetes is characterized by two major defects: a dysregulation of
      pancreatic hormone secretion (quantitative and qualitative--early phase,
      pulsatility--decrease of insulin secretion, increase in glucagon secretion), and
      a decrease in insulin action on target tissues (insulin resistance). The defects
      in insulin action on target tissues are characterized by a decreased in muscle
      glucose uptake and by an increased hepatic glucose production. These abnomalities
      are linked to several defects in insulin signaling mechanisms and in several
      steps regulating glucose metabolism (transport, key enzymes of glycogen synthesis
      or of mitochondrial oxidation). These postreceptors defects are amplified by the
      presence of high circulating concentrations of free fatty acids. The mechanisms
      involved in the "diabetogenicity" of long-chain fatty acids are reviewed in this
      paper. Indeed, elevated plasma free fatty acids contribute to decrease muscle
      glucose uptake (mainly by reducing insulin signaling) and to increase hepatic
      glucose production (stimulation of gluconeogenesis by providing cofactors such as
      acetyl-CoA, ATP and NADH). Chronic exposure to high levels of plasma free fatty
      acids induces accumulation of long-chain acyl-CoA into pancreatic beta-cells and
      to the death of 50% of beta-cell by apoptosis (lipotoxicity).

PMID- 16598901
TI  - [Identification of new genes involved in adipogenesis].

PMID- 16598903
TI  - [Insulin signaling: mechanisms altered in insulin resistance].
AB  - Insulin has a major anabolic function leading to storage of lipidic and glucidic
      substrates. All its effects result from insulin binding to a specific membrane
      receptor which is expressed at a high level on the 3 insulin target tissues:
      liver, adipose tissue and muscles. The insulin receptor exhibits a tyrosine
      kinase activity which leads, first, to receptor autophosphorylation and then to
      tyrosine phosphorylation of substrates proteins, IRS proteins in priority. This
      leads to the formation of macromolecular complexes close to the receptor. The two
      main transduction pathways are the phosphatidylinositol 3 kinase pathway
      activating protein kinase B which is involved in priority in metabolic effects,
      and the MAP kinase pathway involved in nuclear effects, proliferation and
      differentiation. However, in most cases, a specific effect of insulin requires
      the participation of the two pathways in a complex interplay which could explain
      the pleiotropy and the specificity of the insulin signal. The negative control of
      the insulin signal can result from hormone degradation or receptor
      dephosphorylation. However, the major negative control results from
      phosphorylation of serine/threonine residues on the receptor and/or IRS proteins.
      This phosphorylation is activated in response to different signals involved in
      insulin resistance, hyperinsulinism, TNFalpha or increased free fatty acids from
      adipose tissue, which are transformed inside the cell in acyl-CoA. A deleterious
      role for molecules issued from the adipose tissue is postulated in the resistance
      to insulin of the liver and muscles present in type 2 diabetes, obesity and
      metabolic syndrome.

PMID- 16598902
TI  - [Natriuretic peptides: a new lipolytic pathway in human fat cells].
AB  - Human fat cell lipolysis was considered until recently to be an exclusive
      cAMP/protein-kinase A (PKA)-regulated metabolic pathway under the control of
      catecholamines and insulin. Moreover, exercise-induced lipid mobilization in
      humans was considered to mainly depend on catecholamine action and interplay
      between fat cell beta- and alpha2-adrenergic receptors controlling adenylyl
      cyclase activity and cAMP production. We have recently demonstrated that
      natriuretic peptides stimulate lipolysis and contribute to the regulation of
      lipid mobilization in humans. Atrial natriuretic peptide (ANP) and brain
      natriuretic peptide (BNP) stimulate lipolysis in human isolated fat cells.
      Activation of the adipocyte plasma membrane type A guanylyl cyclase receptor (NPR
      A), increase in intracellular guanosine 3',5'-cyclic monophosphate (cyclic GMP)
      levels and activation of hormone-sensitive lipase mediate the action of ANP. ANP
      does not modulate cAMP production and PKA activity. Increment of cGMP induces the
      phosphorylation of hormone-sensitive lipase and perilipin A via the activation of
      a cGMP dependent protein kinase-I (cGK-I). Plasma concentrations of glycerol and
      nonesterified fatty acids are increased by i.v. infusion of ANP in humans.
      Physiological relevance of the ANP-dependent pathway was demonstrated in young
      subjects performing physical exercise. ANP plays a role in conjunction with
      catecholamines in the control of exercise-induced lipid mobilization. This
      pathway becomes of major importance when subjects are submitted to chronic
      treatment with a beta-blocker. Oral beta-adrenoceptor blockade suppresses the
      beta-adrenergic component of catecholamine action in fat cells and potentiates
      exercise-induced ANP release by the heart. These findings may have several
      implications whenever natriuretic peptide secretion is altered such as in
      subjects with left ventricular dysfunction, congestive heart failure and obesity.

PMID- 16598904
TI  - [Gluco-incretin hormones in insulin secretion].
AB  - Nutrient ingestion triggers a complex hormonal response aimed at stimulating
      glucose utilization in liver, muscle and adipose tissue to minimize the raise in
      blood glucose levels. Insulin secretion by pancreatic beta cells plays a major
      role in this response. Although the beta cell secretary response is mainly
      controlled by blood glucose levels, gut hormones secreted in response to food
      intake have an important role in potentiating glucose-stimulated insulin
      secretion. These gluco-incretin hormones are GLP-1 (glucagon-like peptide-1) and
      GIP (gluco-dependent insulinotropic polypeptide). Their action on pancreatic beta
      cells depends on binding to specific G-coupled receptors linked to activation of
      the adenylyl cyclase pathway. In addition to their effect on insulin secretion
      both hormones also stimulate insulin production at the transcriptional and
      translational level and positively regulate beta cell mass. Because the glucose
      dependent insulinotropic action of GLP-1 is preserved in type 2 diabetic
      patients, this peptide is now developed as a novel therapeutic drug for this
      disease.

PMID- 16598905
TI  - [Nutritional epigenomics of metabolic syndrome].
AB  - The importance of epigenetic alterations has been acknowledged in cancer for
      about two decades by an increasing number of molecular oncologists who
      contributed to deciphering the epigenetic codes and machinery and opened the road
      for a new generation of drugs now in clinical trials. However, the relevance of
      epigenetics to common diseases such as metabolic syndrome and cardiovascular
      disease was less conspicuous. This review focuses on converging data supporting
      the hypothesis that, in addition to "thrifty genotype" inheritance, individuals
      with metabolic syndrome (MetS)--combining disturbances in glucose and insulin
      metabolism, excess of predominantly abdominally distributed weight, mild
      dyslipidemia and hypertension, with the subsequent development of obesity, type 2
      diabetes mellitus (T2D) and cardiovascular disease (CVD)--have suffered improper
      "epigenetic programing" during their fetal/postnatal development due to maternal
      inadequate nutrition and metabolic disturbances and also during their life-time.
      Moreover, as seen for obesity and T2D, MetS tends to appear earlier in childhood,
      to be more severe from generation to generation and to affect more pregnant
      women. Thus, in addition to maternal effects, MetS patients may display
      "transgenerational effects" via the incomplete erasure of epigenetic marks
      endured by their parents and grandparents. We highlight the susceptibility of
      epigenetic mechanisms controlling gene expression to environmental influences due
      to their inherent malleability, emphasizing the participation of transposable
      elements and the potential role of imprinted genes during critical time windows
      in epigenetic programming, from the very beginning of development throughout
      life. Increasing our understanding on epigenetic patterns significance and small
      molecules (nutrients, drugs) that reverse epigenetic (in) activation should
      provide us with the means to he obsolete human thrifty genotype into a
      "squandering" phenotype.

PMID- 16598906
TI  - [Cholesterol metabolism modulators in future drug therapy for atherosclerosis].
AB  - Atherosclerosis is a disease characterized by lipid accumulation in the vascular
      wall leading to myocardial infarction or stroke. Hypercholesterolemia is an
      important risk factor and current treatments are largely based on cholesterol
      lowering. In spite of proven efficacy of existing drugs, like statins,
      cardiovascular diseases still remain the most common cause of death in
      industrialised countries. Many new molecular targets are being studied to improve
      atherosclerosis treatment and reduce the number of deaths. The action on these
      targets could lead to a decrease of blood cholesterol levels or produce a direct
      anti-atherosclerotic effect on the vascular wall. A cholesterol lowering effect
      could be achieved by reducing cholesterol synthesis (squalene synthase
      inhibitors), intestinal cholesterol absorption as well as intestinal and liver
      lipoprotein secretion (microsomal transfer protein inhibitors, acyl-coenzyme A
      cholesterol acyltransferase inhibitors) or by increasing fecal excretion of bile
      acids (ileal sodium-dependent bile acid transporter inhibitors). An anti
      atherosclerotic effect on the vascular wall could be achieved by reducing the
      inflammation via activation of peroxisome proliferator activated receptors, or,
      more particularly, could consist of decreased expression of adhesion molecules
      and chemoattractant proteins. Increasing the adenosine triphosphate-binding
      cassette A1 protein and inhibiting acylcoenzyme A:cholesterol acyltransferase 1
      activity could slow down formation of foam cells, which are a hallmark of
      atherosclerosis. Finally, the cholesterol fraction carried by high density
      lipoproteins, which is inversely correlated to cardiovascular risk, could be
      increased by cholesterol ester transfer protein inhibitors. All of these new
      classes of compounds are currently studied by pharmaceutical companies and are in
      different phases of development (preclinical or clinical).

PMID- 16598907
TI  - History and lower extremity physical examination of the pediatric patient.
AB  - The pediatric foot and ankle examination is a specialized yet important skill for
      the modern podiatric medical practitioner. An organized and sequential history
      and physical examination yields a thorough database of information for which to
      establish a successful treatment regimen.

PMID- 16598908
TI  - Metatarsus adductus and skewfoot deformity.
AB  - Metatarsus adductus deformity should be recognized and addressed appropriately
      and in a timely fashion so as to achieve an effective correction with low rates
      of recurrence. Early diagnosis and treatment are of paramount importance, because
      spontaneous resolution is rare. Although nonoperative treatment is desirable via
      manipulation and soft tissue stretching and serial cast immobilization,
      appropriate surgical intervention needs to be used on occasion to achieve
      correction of resistant cases. Depending on the severity and flexibility of the
      deformity and the age of the patient, various methods of surgical reconstruction
      are available. A long-standing untreated or undertreated adductus deformity can
      lead to the formation of a skewfoot deformity with more significant symptoms and
      deformity. Treatment of this deformity is rarely successful by nonoperative
      means, and appropriate surgical procedures addressing the metatarsal adductus
      component and the flatfoot component can be used for correction of the
      dysfunctional or symptomatic skewfoot.

PMID- 16598909
TI  - Talar neck osteotomy for flatfoot reconstruction: a 27-year follow-up study.
AB  - The talar neck osteotomy is done at the junction of the head and neck of the
      talus, frequently in conjunction with desmoplasty and posterior tibial tendon
      advancement. This is done effectively to correct severe deformities involving the
      talus. The correction produces a structural realignment of the talar head.
      Adjunctive procedures are also done when these are deformities involving the
      posterior column, lateral column, and/or medial column. A 27-year follow-up study
      is presented containing data from 215 procedures on 117 patients with a minimum
      of one year follow-up.

PMID- 16598910
TI  - The algorithmic approach to pediatric flexible pes planovalgus.
AB  - The author presents an alternative approach to the pediatric flexible pes
      planovalgus patient. Hopefully, this algorithm can serve as a guide and not as a
      rule. It is meant to serve the foot and ankle surgeon as a means of eliminating
      the arbitrary assignment of a flatfoot to procedures. Instead, the algorithm
      assigns procedures to a type of flatfoot. The specific procedures listed are a
      guide to reduce our failures while continually improving our successes.

PMID- 16598911
TI  - Difficult and controversial pediatric cases: a roundtable on conservative and
      surgical management.
AB  - Pediatric clinical management is highly specialized. Problems are complex and
      often complicated by other medical issues that dictate limitations on therapeutic
      options. Appropriate diagnosis and successful clinical management depend on the
      experience and skill of the surgeon. This roundtable discussion focuses on seven
      difficult cases and presents the views of three experienced and skilled experts
      in the field.

PMID- 16598912
TI  - The Ponseti technique for treatment of talipes equinovarus.
AB  - Traditional treatment for clubfoot usually includes initial casting and an
      extensive posterior medial soft tissue release with biplanar pinning, followed by
      more casting. This treatment has significant risks, complications, and the
      potential for a poorer prognosis as the patients age, usually with stiff and
      scarred feet. In contradistinction, Ignacio Ponseti has been using his unique
      technique of clubfoot manipulation, casting, and Achilles tenotomy for more than
      50 years with a high degree of success. Currently, there are many peer-reviewed
      and independently verified studies that replicate his success in treating
      clubfoot. This technique is easy to learn and is becoming the accepted treatment
      of idiopathic clubfoot all over the world.

PMID- 16598914
TI  - Fractures and dislocations of the foot in children.
AB  - The challenge of managing pediatric foot injuries is the identification of the
      rare injuries that require operative treatment and the management of
      complications such as compartment syndrome, post-traumatic foot deformities, and
      avascular necrosis. With these complications in mind, the authors discuss
      fractures of the talus, calcaneus, lesser tarsal bones, Lisfranc's joint,
      metarsals, and phalanges. Dislocation of metatarsophalangeal or interphalangeal
      joints is also discussed.

PMID- 16598913
TI  - External fixation for the foot and ankle in children.
AB  - During the last decade, external fixation for the pediatric foot and ankle has
      evolved as a result of advances in technology (eg, Taylor spatial frame,
      hydroxyapatite-coated external fixator pins) and preoperative deformity planning.
      Although complications are common, most are minor and can be addressed
      nonoperatively while treatment continues. This article reviews the indications
      and applications of external fixation for soft tissue contractures, idiopathic
      and teratologic clubfoot, osteotomies, metatarsal lengthening, tibial
      lengthening, and foot and ankle trauma.

PMID- 16598915
TI  - Preconditioning principles for preventing sports injuries in adolescents and
      children.
AB  - Preseason preconditioning can be accomplished well over a 4-week period with a
      mandatory period of rest as we have discussed. Athletic participation must be
      guided by a gradual increase of skills performance in the child assessed after a
      responsible preconditioning program applying physiologic parameters as outlined.
      Clearly, designing a preconditioning program is a dynamic process when accounting
      for all the variables in training discussed so far. Despite the physiologic
      demands of sport and training, we still need to acknowledge the psychologic
      maturity and welfare of the child so as to ensure that the sport environment is a
      wholesome and emotionally rewarding experience.

PMID- 16598916
TI  - Sports injuries in the pediatric and adolescent foot and ankle: common overuse
      and acute presentations.
AB  - Care of the youth athlete requires knowledge of developmental anatomy and
      specific injury patterns, which are acute or chronic in nature. We may expect
      that the incidence of overuse and acute foot and ankle injuries in this
      population is likely to increase in proportion to the number and intensity of
      competitive youth teams with demanding training schedules. We, as physicians,
      must exercise our best judgment in regard to recognizing these patterns early and
      instituting appropriate treatments. Return to play decisions should be based on
      objective criteria when available and always keeping the best interest of the
      athlete's future health in the forefront of our minds.

PMID- 16598918
TI  - [Study on manpower allocation criteria of center of disease prevention and
      control in the context of province level, city level and county level].
AB  - OBJECTIVE: To set the manpower allocation criteria of center of disease
      prevention and control. METHODS: Expected allocation manpower criteria was
      obtained through adjusting the current manpower allocation of disease prevention
      and control centers. The principle was to fulfill public function and promote
      professional efficiency. RESULTS: Based on function requirement, in 3 - 5 years,
      the manpower allocation criteria of center of disease prevention and control at
      provincial-level is 336 persons, at city-level is 102 persons, and at county
      level is 33 persons, that means in whole country 140016 persons should be needed.
      In 10 years, the manpower allocation criteria of center of disease prevention and
      control at provincial-level is 386 persons, at city-level is 112 persons, and at
      county-level is 38 persons, that means in whole country 159086 persons should be
      needed. CONCLUSION: The manpower allocation criteria advanced in the study
      indicated that current manpower quantity should be greatly reduced. It is an
      inevitable trend that disease prevention and control centers reduce the staff
      quantity and promote their quality.

PMID- 16598919
TI  - [Construction of "pEGFP-C1-pU6-dsRNA" recombinant for human DNA polymerase beta
      RNA interference].
AB  - OBJECTIVE: To clone the "pEGFP-C1-pU6-dsRNA" recombinant for human DNA polymerase
      beta RNA interference, to provide research tool for the study on the function of
      DNA polymerase beta in repairing of human DNA damaged by environmental chemical
      pollutants (ECPs). METHODS: According to the gene sequence of polymerase beta
      cDNA published in Genbank, double strand RNA(dsRNA) sequence which was used in
      RNA interference was designed by dsRNA oligonucleotide designer and synthesized
      by chemical methods. DNA recombination technology was used to insert the up
      related dsRNA sequence into the vector of pSIREN-RetroQ, and then the "pSIREN
      RetroQ-dsRNA" recombinant was obtained. After E. coli DH5alpha was transformed
      with the "pSIREN-RetroQ-dsRNA" recombinant and screened with ampicillin for
      positive clones, plasmid was extracted and digested by EcoR I and Bgl II , the
      fragment of"pU6-dsRNA"was purified. And then the "pU6-dsRNA"fragment was cloned
      into the vector of pEGFP-C1 by recombination technology, the recombinant of
      "pEGFP-C1-pU6-dsRNA" was obtained and identified by restriction endonuclease
      analysis and sequencing. RESULTS: The "pEGFP-C1-pU6-dsRNA" recombinant lied in
      the predicted band, and the sequence of insert was identical to the designed
      target fragment. CONCLUSION: The "pEGFP-C1-pU6-dsRNA" recombinant was
      successfully cloned for human DNA polymerase beta RNA interference, it was an
      important research tool for the further study.

PMID- 16598921
TI  - [Construction of short hairpin RNA vector of inhibiting poly ADP-ribose
      polymerase activity].
AB  - OBJECTIVE: To construct expressing vector of short hairpin RNA (shRNA) in order
      to inhibit human PARP1 activity. METHODS: 2 pairs of 64 base oligos for hairpin
      RNA expression which targeted PARP1 gene were chemically synthesized and annealed
      then ligased with pSIREN-RetroQ vector with BamH II and EcoR I . Cut by EcoR t
      and Bgl II, shRNA and its upstream U6, which have 330 bp, were inserted into the
      same treated pEGFP-C1 vecter to construct GFP expression plasmids that inhibited
      hPARP1 protein shRNA plasmid (pEGFP-C1P). Oligos with a scrambled sequence were
      used as a negative control. RESULTS: Recombinant pEGFP-C1P1, pEGFP-C1P2 and pEGFP
      C1N vectors was identified by digestion with EcoR I and Bgl II and confirmed by
      sequencing analysis with U6 primer. The results demonstrated that the 330 bp had
      been inserted into the expected site. Furthermore, the insertion sequence was
      exactly correct. CONCLUSION: pEGFP-C1-shRNA system has been constructed
      successfully. This will facilitate the study of PARP1's DNA repairing function.

PMID- 16598920
TI  - [Screening of aryl hydrocarbon receptor gene specific RNA interference fragment
      by quantitative competitive RT-PCR].
AB  - OBJECTIVE: To evaluate and screen the specific RNAi fragments which can
      effectively inhibit Aryl hydrocarbon receptor(AHR) gene mRNA expression in human
      bronchial epithelial cell line (16HBE). METHODS: AHR mRNA of 16HBE cells
      transfected 4 different AHR gene interfere sites were determined quantitatively
      with the quantitative competitive RT-PCR by using self-prepared internal standard
      as competitive templates, and the RNA interfere effect wasevaluated. RESULTS: AHR
      mRNA average expression per 40ng total RNA of 16HBE cells transfected 4 different
      AHR gene interfere fragments were 5.65fg, 14.78fg, 3.14fg and 0.68fg
      respectively, the average rates of inhibition were 61.6%, -0.5%, 78.6% and 95.4%
      respectively. CONCLUSION: AHR gene specific effective RNA interfere sequence ware
      screened by quantitative competitive RT-PCR which could accurately quantify gene
      mRNA level, and offered condition for studying the gene function of AHR.

PMID- 16598922
TI  - [Detection of estrogenic effects of nonylphenol and bisphenol A in vitro reporter
      gene-based assays].
AB  - OBJECTIVE: To explore the estrogenic effects and disruptive mechanism of NP and
      BPA by reporter gene-based assays we developed. METHODS: pERE-Luc plamid was
      generated by inserting estrogen response element (ERE) fragment into MCS of pGL3
      promoter vector. MCF7 cells were cotransfected with pERE-Luc and phRL-SV40 using
      Sofast transfection reagent. The cells then treated with 17beta-estradiol (E2),
      tamoxifen (Tam), nonylphenol(NP) and bisphenol A (BPA) and expression of the
      repoter gene in the cell lysates was assayed using Dual-Lucferase reporter assay
      system. RESULTS: The pERE-Luc plasmid was constructed. Luciferase activities of
      MCF7 cells transfected pERE-Luc showed dose-responed realitionship with E2. 1 x
      10(-11) mol/L E2 could induce the expression of reporter gene and 1 x 10(-9)
      mol/L E2 resulted in the largest luciferase activity. E2 couldn't induce the
      luciferase activity without pERE-Luc. Tam is a complete antagonist, inhibited the
      E2-induced luciferase expression. NP induced the luciferase activity at
      concertrations > 1 x 10(-6) mol/L, BPA induced the luciferase activity at
      concertrations > 1 x 10(-6) mol/L. The estrogenic activity of NP was more than
      BPA. CONCLUSION: The assay we established is usful, NP and BPA showed estrogenic
      activities.

PMID- 16598923
TI  - [Effect of heat and BPDE on the expression of Hsp27 and Hsp70 in A549 cell line].
AB  - OBJECTIVE: To investigate the expression of the Hsp27 and Hsp70 in A549 cells
      treated with heat and BPDE. METHODS: A549 cells cultured in vitro were divided
      into heat stress group and BPDE group. Cells cultured at 37 degrees C used as
      control. The heat stress group was exposed to heat at different temperature (39
      degrees C, 42 degrees C and 43 degrees C) for 2h. The BPDE group was treated with
      different concentrations of BPDE (0, 2, 4 and 8 micromol/L). Western-blot was
      used for the Hsp27 and Hsp70 expression analysis. RESULTS: In heat stress group,
      Hsp27 expression levels significantly increased compared to the control (P <
      0.05) and reached its peak at 39 degrees C. Hsp70 expression level also increased
      after heat stress. It reached the peak at 42 degrees C and was higher than that
      of the control with significance (P < 0.05). In BPDE group, Hsp27 and Hsp70
      expression levels were higher than those of the control. Hsp27 reached a maximum
      at 8 micromol/L, the highest concentration of BPDE in this experiment, and was
      significantly higher than that of the control (P < 0.05). But it was still on its
      elevatory phase. Hsp70 reached its peak at 4 micromol/L and was significantly
      higher than that of the control at 4 micromol/L and 8 micromol/L. CONCLUSION:
      Both heat and BPDE can induce the expressions of Hsp27 and Hsp70. In heat stress
      group, the Hsp27 and Hsp70 levels reached their peaks at 39 degrees C and 42
      degrees C. In BPDE group, the expressional levels of Hsp27 and Hsp70 reached
      their peaks at 8 micromol/L and 4 micromol/L.

PMID- 16598925
TI  - [Biodegradation of dibutyl phthalate by diatomite adsorptive immobilized
      microorganism].
AB  - OBJECTIVE: To study the biodegradation characteristics of seeding type
      immobilized microorganism on dibutyl phthalate (DBP). METHODS: The immobilized
      microorganism was made to adsorb DBP degradation dominant bacteria by using
      modified diatomite as carrier, then it degraded DBP under different primary
      concentration, vibration rate, pH, temperature and at the presence of metal
      compounds. The degradation kinetics was analyzed. RESULTS: When DBP primary
      concentration was 100-500 mg/L, the adsorptive immobilized microorganism could
      maintain relatively high activity and the DBP degraded rate was above 80% in 24h.
      Dissociative and immobilized microorganism could get higher degradation activity
      in vibration than in stillness. When pH was 6.0 - 9.0, the degradation rate of
      immobilized microorganism on DBP was above 82% in 24h and its activity is higher
      than dissociative microorganism. In the range of 20 degrees C to 40 degrees C,
      the DBP degraded rate by immobilized microorganism could reach 84.5% in 24h. If
      mental compounds existed in the DBP water sample, the degradation activities of
      dissociative and immobilized microorganism were inhibited obviously. The form of
      DBP degradation kinetics could be described as the first-order model. CONCLUSION:
      The immobilized microorganisms using diatomite as carrier could degrade DBP
      effectively. The adsorptive immobilized microorganism was more adapted to DBP
      load, temperature and pH than dissociative microorganism. The mental compounds
      could inhibited their activities. The degradation reaction of adsorptive
      immobilized microorganisms on DBP was according with the first-order model.

PMID- 16598924
TI  - [Association of cadherin CDH23 gene polymorphisms with noise induced hearing loss
      in Chinese workers].
AB  - OBJECTIVE: To investigate the association of cadherin 23 gene (CDH23)
      polymorphisms with the development of noise induced hearing loss (NIHL). METHODS:
      194 workers exposed to occupational noise were drawn as the subjects in the cross
      sectional epidemiology study. According to the result of audiometry, they were
      divided into two groups: the NIHL group and the normal group. The genotypes of 93
      workers with NIHL and 101 normal workers were tested by polymerase chain reaction
      followed by restriction fragment polymorphism analysis (PCR-RFLP). RESULTS: There
      were no significant difference in the distribution of genotypes and alleles
      frequencies of the rs1227049 and rs1227051 positions between NIHL group and
      normal group (P > 0.05), there were significant differences between the two
      groups in the rs3802711 position and the terminal position of exon 7 (P < 0.01).
      After adjusted for age, sex, smoking, history of explosive noise exposure and
      cumulative noise exposure (CNE) with multiple logistic regression analysis, the
      risk of rs1227049 CC genotype was found significantly increased than that of the
      GG genotype, the OR value of which was 3.865 (95% CI 1.076 - 13.886), the risk of
      rs3802711 TT genotype was significantly higher than that of the CT genotype, the
      OR value of which was 6.088 (95% CI 2.485 - 14.917). GG genotype in the terminal
      position of exon 7 was also found a significantly higher risk than the AG
      genotype, the OR value of which was 5.769 (95% CI 2.745 - 12.121). CONCLUSION: It
      was suggested that genetic polymorphism in cadherin CDH23 gene might play an
      important role in the development of NIHL in Chinese workers. The individuals
      with the rs1227049 CC genotype, rs3802711 TT genotype and GG genotype in the
      terminal position of exon 7 might be more susceptible to NIHL.

PMID- 16598926
TI  - [Effect of PM2.5 collected during the dust and non-dust periods on the viability
      and gap junctional intercellular communication in human lung fibroblasts].
AB  - OBJECTIVE: To investigate the effects of PM2.5 collected during the dust and non
      dust periods on the viability and gap junctional intercellular communication
      (GJIC) in human lung fibroblasts. METHODS: Human lung fibroblasts were treated
      with PM2.5 suspension and its organic and inorganic extracts at various
      concentrations for 24 h. The cellular viability was measured with MTT methods,
      and the GJIC between human lung fibroblasts was detected by the scrape loading
      dye transfer assay. RESULTS: PM2.5 suspension from both sources and the inorganic
      extracts of dust PM2.5 significantly decreased the viability of human lung
      fibroblast in a dose-dependent manner. Compared with other preparations, the dust
      PM2.5 suspension had the highest effect. Gap junctional intercellular
      communication between human lung fibroblasts was significantly inhibited by the
      different composition of PM2.5 from both sources in a dose-dependent manner. The
      inhibitory effects on GJIC were in the order of organic extract of PM2.5 >
      suspension > inorganic extract. CONCLUSION: Composition and source of PM2.5 are
      important factors which influnce the toxic effects on cells. The composition of
      PM2.5 from both sources can inhibit GJIC, suggesting decreasing GJIC may be
      related to the biological mechanisms of toxicity caused by PM2.5.

PMID- 16598927
TI  - [Effect of environmental contaminants on DNA methyltransferase activity of mouse
      preimplantation embryos].
AB  - OBJECTIVE: To investigate the effect of environmental contaminants on development
      rate and DNA methyltransferase activity of preimplantation embryos. METHODS: 1
      cell embryos were collected from oviduct, in vitro cultured to blastocyst stage
      in media with or without environmental contaminants. The development rate and DNA
      methyltransferase activity were determined. RESULTS: The development rates of
      preimplantation embryos from 1-cell stage to blastocyst stage were not affected
      by the exposed compounds. However, 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)
      significantly increased the DNA methyltransferase activity, 2, 2', 3, 3' 4, 4'
      polychlorinated biphenyl (PCB153) and diethylstilbestrol (DES) significantly
      decreased the DNA methyltransferase activity, while p, p'- dichlorodiphenel
      ethylene (DDE) and dibutyl phthalate (DBP) did not change the DNA
      methyltransferase activity significantly. CONCLUSION: Exposure to TCDD, DES, and
      PCB 153 alters the DNA methyltransferase activity in early development stage,
      which may induce the change of methylation status of genes and affect the
      development in the later stage.

PMID- 16598928
TI  - [Establishment and application of fetal rolling palate organ culture model of
      mouse].
AB  - OBJECTIVE: To investigate the effect of all-trans retinoic acid (atRA) on the
      development of mouse palates and its possible mechanism, a model of fetal mouse
      rolling plate organ culture was establishted. METHODS: Mouse embryonic palates
      were explanted on GD12 and cultured in a roller device for 72h induced by atRA in
      different concentrations from 10(-5) micromol/L to 10(-1) micromol/L. RESULTS:
      Similar to development in vivo, palates in control normal fused. Compared with
      the control, palates development and fusion were promoted in group of 10(-15)
      micromol/L, while were inhibited in groups of 10(-4) micromol/L or greater,
      resulting in cleft palate. The proportion of fusion was reduced in a significant
      dose-response pattern. CONCLUSION: In the model, the cultured palates continued
      developing and fusing. Palatal fusion was promoted by normally atRA in 10(-5)
      micromol/L level and were inhibited by atRA in 10(-4) micromol/L level or
      greater, which resulting in cleft palate. These mentioned confirm the validity
      and reliability of this model.

PMID- 16598929
TI  - [Antagonism of vitamin E on lipid peroxidation in testis of male rats with carbon
      disulfide].
AB  - OBJECTIVE: To study the antagonistic joint action of vitamin E (VE) lipid
      peroxidation of testis in the male rats with carbon disulfide (CS2). METHODS: 36
      wistar male rats were randomly dicided into six groups. It took 10-week for the
      rats to breath CS2 in different concentrations (0, 50, 250 and 1250 mg/m3),
      respectively, CS2 (1250 mg/m3) with VE (250 mg/kg diet) and VE (250 mg/kg diet)
      group. After 10-week treatment, rats were killed and the following parameters of
      lipid peroxidation in testis were determined:SOD, MDA, GST, GSH, GSH-px, NO, NOS
      and iNOS. RESULTS: Compare with the control group, SOD, GST, GSH-px, NOS and iNOS
      activity were decreased (P < 0.05 or P < 0.01), GSH, NO content decreased also,
      MDA content was increased (P < 0.01). After the antioxidant VE treatmented, the
      parameters were significantly increased (the amount of MDA was decreased).
      CONCLUSION: The antioxidant VE significantly protects against on lipid
      peroxidation in testes of male rats with CS2.

PMID- 16598930
TI  - [Serophysiological study on the effects of high-fat diet on proliferation of
      human lung adenocarcinoma cell line SPCA1].
AB  - OBJECTIVE: The present study was designed to assess the effect of the diet high,
      in fat on proliferative activities of lung adenocarcinoma cell line SPCA1 by
      means of serophysiological method at the cell level. METHODS: Female Sprague
      Dawley rats were fed with common chow or high-fat diet (lard : common chow = 1 :
      9) for 7 weeks after having ascertained the suitable conditions for cell culture
      in serophysiological study. Then the serum from the rat fed with different diet
      was obtained and used for culturing human lung adenocarcinoma cell line SPCA1.
      The cells were harvested and used for analysis in MTT assay, [3H] thymidine
      incorporation trial and flow cytometric analysis to identify cell proliferative
      activity, DNA duplication and cell cycle distribution, which were examined to
      discuss the effects of rat's serum treated with high-fat diet (RSTHFD) on
      proliferation of cancer cells. RESULTS: (1) Fifteen percent of inactivated rat
      serum supplemented in culture medium was suitable condition for culturing human
      lung adenocarcinoma cell line SPCA1. (2) RSTHFD can accelerate DNA duplication,
      cell proliferation and cell mitosis. CONCLUSION: (1) Serophysiological methods
      can be used to study the effects of diet on proliferation of SPCA1 cell line. (2)
      High-fat diet can stimulate the proliferative activity of SPCA1 cells in the
      present study.

PMID- 16598931
TI  - [Effects of chromium and fish oil on the level of leptin and insulin in obese
      rats].
AB  - OBJECTIVE: In order to study the effects of chromium and fish oil on the level of
      leptin and insulin in obese rats, 32 obese model rats were divided randomly into
      four groups: fish oil group (5 ml/kg bw), chromium group (3 mg/kg bw), fish oil +
      chromium group and high fat diet group. METHODS: In the end of the experiment (6
      weeks) fats around kidney and spermary were weighted and blood samples were
      collected to determine the level leptin and insulin. RESULTS: The results showed
      that the level of leptin and insulin in experimental groups were lower than those
      in high fat diet group. The ratios of fats around kidney and/or around spermary
      to body weight in experimental groups were lower than those in high fat diet
      group. CONCLUSION: Chromium and fish oil possible depress the high level of
      leptin and insulin in obese model rats.

PMID- 16598932
TI  - [Effects of soy isoflavone on gene expression of adiponectin in insulin
      resistance rats induced by high-fat and high-sugar diet].
AB  - OBJECTIVE: To study the effects and mechanisms of soy isoflavone (SIF) on
      improving insulin resistance (IR) status in IR rats induced by high-fat and high
      sugar diet. METHODS: IR rats induced by high-fat and high-sugar diet were
      assigned into four groups and gavaged with SIF at doses of 0 (model control
      group), 50, 150 and 450 mg/kg bw for 4 weeks, respectively. Insulin, glucose,
      adiponectin in serum and adiponectin mRNA in perirened adipocyte were detected.
      RESULTS: Compared with model control group, body weight and fat pad weight were
      lower, and serum adiponectin and adiponectin mRNA expression were higher in the
      450 mg/kg bw group, insulin and insulin-resistance index were lower in the 150
      mg/kg bw group and 450 mg/kg bw. There is no differences in plasma glucose levels
      among groups. There is an negative correlation between insulin-resistance index
      and serum adiponectin level (Y = 24.802 - 2.856X, r = - 0.881, n = 47, P < 0.01).
      CONCLUSION: These results suggest that soy isoflavone may decrease adipose
      deposition, increase serum adiponectin level, and ameliorate insulin sensitivity.

PMID- 16598933
TI  - [Relation between peptide YY 3-36 and dietary induced obesity resistant rats].
AB  - OBJECTIVE: To study the plasma concentration of peptide YY3 - 36 (PYY3-36) and
      the expression levels of PYY mRNA of ileum and colon in dietary induced obesity
      (DIO) and dietary induced obesity resistant (DIO-R) rats and the relation between
      PYY3-36 and DIO-R rats. METHODS: Thirty-six female SD rats were randomly divided
      into high-fat diet group (n = 27) and chow fed control group (n = 9), after 13
      weeks of either a high-fat diet or chew fed diet, the high-fat diet group was
      subdivided into DIO and DIO-R group according to the final body weight. Weight
      gain, caloric intake, the concentration of PYY3-36 and the expression levels of
      PYY mRNA were measured and compared. RESULTS: The total caloric intake of DIO-R
      rats was lower than DIO rats (P < 0.01), while no significant difference was
      found between DIO-R and control rats (P > 0.05). The concentration of PYY3-36 and
      the expressions of PYY mRNA of ileum and colon in DIO-R rats were higher
      significantly than that of the DIO and control rats (P < 0.01), while no
      significant difference was found between DIO and control group (P > 0.05), except
      that PYY mRNA of ileum was advanced in DIO group (P < 0.01). CONCLUSION: On the
      High-fat diet, SD rats showed different susceptibility to obese and energy
      intake, increased levels of PYY3-36 and PYY mRNA might be related to dietary
      induced obesity resistant.

PMID- 16598934
TI  - [Effect of selenium supplement on the disordered lipid metabolism induced by the
      overdose of iodine in mice].
AB  - OBJECTIVE: To explore the effect of selenium supplement on the disordered lipid
      metabolism induced by the overdose of iodine in mice. METHODS: The 80 Balb/c mice
      were randomly divided into eight groups, the normal control group, the high
      iodine group (drunk the water containing iodine 3000 microg/L) and six selenium
      groups (drunk the water containing iodine 3000 microg/L and selenium 0.1, 0.2,
      0.3, 0.4, 0.5, 0.75 mg/L). The total cholesterol and triglyceride in serum and
      liver were determined. RESULTS: The total cholesterol in serum, the total
      cholesterol and triglyceride in liver of high-iodine group increased
      significantly compared with normal control group. There is no difference between
      normal control group and the group drunk the water contained 0.2 mg/L selenium.
      CONCLUSION: It suggests that it is an effective intervention dosage to drunk
      water containing 0.2 mg/L selenium.

PMID- 16598935
TI  - [Effect of selenium deficiency on the F344 inbred line offspring rats' neuro
      behavior, ability of learning and memory].
AB  - OBJECTIVE: To establish the selenium (Se) deficient animal model on F344 inbred
      line rats and observe the effects of a long-term Se-deficiency on the offspring's
      neuro-behavior, abilities of learning and memory. METHODS: Feeding F344 inbred
      line rats on Se-deficient diet to establish Se-deficient animal model. For the
      offspring, the body weight, physiological indexes nervous reflections for growth
      and development were monitored during the early postnatal period. RESULTS: The Se
      deficient diet contained less than 0.01 mg/kg and the glutathione peroxidase (GSH
      Px) activity in blood of the Se-deficient group rats is lower than the Se-normal
      group after feeding on Se-deficient diet for 4 weeks. For the offspring, the
      birth weight and the body weight of Se-deficient group were obviously lower than
      the Se-normal group before weaning. Se-deficient offspring rats differed from Se
      normal controls in lower scores in surface righting reflex (RR) test at postnatal
      4th day after delivery, cliff avoidance test at postnatal 7th day and auditory
      acuity trial at postnatal 10th day respectively. But these differences disappear
      after a few days in the same tests. In addition, no significant differences
      between two groups in suspending test and walking ability test at postnatal 12th
      and 14th day. In open field test, Se-deficient male offspring stayed less time in
      the middle grid and moved less. In Morris water maze test, the Se-deficient
      offspring spent more time to find the hidden platform at the 6th and 9th training
      tests in the place navigation trial. Furthermore, the Se-deficient group spent
      less time in target quadrant when giving the spatial probe trial. CONCLUSION: A
      Se-deficient animal model have been established on F344 inbred line rats
      successfully. A long-term Se deficiency could retard the development of the
      offspring in uterus and after delivery. Se deficiency also decreased the
      offspring's abilities of spatial learning and memory in Morris water maze test
      and resulted in the male offspring's nervousness to new stimulant.

PMID- 16598937
TI  - [2000 Chinese total dietary study--the dietary arsenic intakes].
AB  - OBJECTIVE: To assess the safety of dietary arsenic intakes in different areas in
      China. METHODS: Using the total dietary study method, the analytical samples were
      obtained in different areas by food consumption survey, food aggregation, food
      sampling and preparation. The levels of dietary total and inorganic arsenic were
      determined by the hydride generation atomic absorption spectrometry and atomic
      fluorospectrophotometry. The dietary total and inorganic arsenic intakes in
      different areas were obtained by timing the food consumption data and the arsenic
      content in different dietary samples. The safety of dietary arsenic was evaluated
      in Chinese four regions and average adults by using the dietary inorganic arsenic
      PTWI recommended by WHO. RESULTS: The results indicate that the dietary arsenic
      intake is safety in different regions. Only a few samples in some areas exceed
      tolerance limits of China national standard. Dietary total and inorganic arsenic
      (of PTWI) intakes in four different regions (north1, north2, south1, south2 and
      average adults) were 0.220 mg and 0.094 mg (69.3%), 0.254 mg and 0.098 mg
      (72.2%), 0.296 mg and 0.048 mg (35.6%), 0.335 mg and 0.077 mg (57.3%), 0.276 mg
      and 0.079 mg (58.6%) respectively. Mainly sources of dietary arsenic intake were
      cereals, vegetables and beverage and water. CONCLUSION: It is the first time that
      the dietary total arsenic and inorganic arsenic intakes of the adult were
      investigated in Chinese total diet study. The result shows that the total and
      inorganic arsenic intakes in Chinese people are safe.

PMID- 16598936
TI  - [Evaluation on beta-carotene-vitamin A equivalence of middle-aged subjects in
      Chinese adults].
AB  - OBJECTIVE: As an extended study of beta-Carotene-vitamin A equivalence in Chinese
      adults, we carried out an experiment on 10 (5 males and 5 females) rural
      volunteers aged 38 - 49 years, which would be complementary to the early reported
      study on subjects aged 50 - 60 years. METHODS: Ten healthy Chinese adult
      volunteers aged 38-49 years were recruited in a 56 days experiment, which
      included residency in the Metabolic Research Unit (first 10 days and in home
      (last 46 days). A physiological dose of 2H8 beta-C (11,011 (nmole or 6 mg) in oil
      was given with a liquid diet (25% energy from fat) to the volunteers in the first
      day of the experiment. Three days after the 2H8 beta-C, each volunteer took a
      reference dose of 2H8 retinyl acetate (8,915 nmole or 3 mg) in oil with the same
      liquid diet. Serum samples were collected at 0, 3, 5, 7, 9, 11 and 13 hours of
      the first and the fourth days of study, and fasting serum samples were also
      collected daily in first 10 days and then weekly at morning of 14th, 21st, 28th,
      35th, 42nd, 49th and 56th day after a 12-hours overnight fast. Serum retinol and
      carotenoids concentrations were measured by high performance liquid
      chromatography (HPLC). Also retinol fraction was extracted from serum and
      isolated by HPLC. The serum retinal enrichments were determined by using gas
      chromatograph/mass spectrometry with electron capture negative chemical
      ionization (GC-MS). RESULTS: The average 52-day area under the serum 2H4 retinol
      response curve (from the 2H8 beta-C dose) was (1289 +/- 547) nmol/d and the 52
      day area under the serum 2H8 retinol response curve (from the 2H8 retinyl acetate
      dose) was (3560 +/- 1058) nmol/d. By using 2H8 retinyl acetate as the vitamin A
      reference, the 2H4 retinol formed from 2H8 beta-C (11,011 nmol) was calculated to
      be equivalent to (3434 +/- 1449) nmol of retinol. The calculated conversion
      factor of beta-C to retinol ranged from 2.00 - 9.61 to 1 with an average of (3.89
      +/- 2.76) to 1 on a molar basis, or 3.76 - 18.05 to 1 with an average of (7.30 +/
      5.18) to 1 on a weight basis. CONCLUSION: The conversion of beta-C to vitamin A
      in 10 middle-aged Chinese adults had been quantitatively determined by using a
      stable isotope reference method, and an average conversion ratio of 7.30 : 1 to 1
      on a weight basis was found in this study.

PMID- 16598938
TI  - [Evaluation on the dietary iron absorption by young Tibetan men using stable
      isotopic tracer].
AB  - OBJECTIVE: The study was aimed to evaluate the iron absorption in the Tibetan
      man's diet using the stable isotopic iron, and present a reference to improve the
      dietary iron absorption for Chinese. METHODS: In the study conducted on the spot
      of high altitude (> 3500m), the iron tracer (FeSO4 enriched with 57Fe) and the
      recovery indicator dysprosium (Dy) were orally administrated to 16 young Tibetan
      men, and their feces were sampled. The ratios of 57Fe/56Fe in fecal samples was
      determined by inductively coupled plasma mass spectrometry, and then the iron
      absorption was calculated based on the principle of isotope dilution. RESULTS:
      The rate of dietary iron absorption in young Tibetan men was 13.4% +/- 6.4% with
      good linear correlation between daily fecal excretions of iron tracer and Dy.
      CONCLUSION: Dy had the same behavior as non-absorbed iron tracer in the digestive
      tract and the recovery of Dy may indicate the completeness of fecal collection.
      Dietary iron absorption in the adult Tibetan man was relatively high.

PMID- 16598939
TI  - [Comparison of transferrin receptor between child-bearing period women and
      children].
AB  - To compare plasma TfR, ferritin concentrations and their ratios in children and
      child-bearing period women and look for correlation between TfR concentration and
      other measures of iron status. METHODS: Our study groups were healthy 3-6-year
      old preschool girls (n = 109), 11-12-year-old prepubertal girls (n = 133) and 20
      45-year-old childbearing period women (n = 115). Plasma TfR concentration, SF
      concentration and TfR/SD were compared in different groups. The correlation of
      TfR and other indexes were studied. RESULTS: TfR concentrarions were higer in
      preschool girls [(23.34 +/- 6.78) nmol/L] than in prepubertal girls [(21.33 +/-
      5.30) nmol/L] and higher in prepubertal girls than in childbearing period women
      [(19.86 +/- 4.83) nmol/L]. SF concentrations were higher in prepubertal girls
      [(60.37 +/- 33.39) microg/ L] than in child-bearing women [(57.17 +/- 29.81)
      microg/L] and higher in child-bearing women than in preschool girls [(47.83 +/-
      24.49) microg/L]. TfR/SF ration were higer in preschool girls (0.72 +/- 0.83)
      than in prepubertal girls (0.48 +/- 0.47) and higher in prepubertal girls than in
      child-bearing period women (0.47 +/- 0.37). By multiple regression analysis, the
      predictors of TfR concentration were plasma ferritin, hemaglobin and age.
      CONCLUSION: Plasma ferritin, Hb and age, even within the normal physiologic SF,
      Hb, influence TfR concentrations. The lower the iron stores, the stronger the
      influence of ferritin on TfR. The TfR concentrations are higher in children than
      adults respongsing to physiologically low iron stores in children.

PMID- 16598941
TI  - [Production purification and characterization of polyantibodies against
      microcystin-LR].
AB  - OBJECTIVE: Production and characterization the polyantibodies against MCYST-LR.
      METHODS: microcystin-LR (MC-LR) was conjugated to KLH, then immune the rabbit by
      the routine method. Purify the antiserum by centrifugal and saturated sulfuric
      ammonium precipitated methods. Count the affinity constant and measure the
      titers, IC50 Value and the sensitivity. RESULTS: The titers of the antiserum is
      over 25600. IC50 value is about from 0.1 ng/ml to 1 ng/ml. The across-reactivity
      ratio to MC-LW and MC-LR is about from 0.1% to 20%.

PMID- 16598940
TI  - [Control the increasing of the prevalence of overweight and obesity by covering
      the energy gap of Chinese population].
AB  - OBJECTIVE: To estimate the quantity of the excess energy accumulation according
      to the weight change in a follow up population. Confirm the energy gap and give
      the quantitative goal for how much change in energy balance is needed. METHODS:
      This paper was based on data collected in the China Health and Nutrition Survey.
      We selected the adults, 20-45 years old healthy men and women, who took part in
      the survey in 1989 and were followed up in 2000. RESULTS AND CONCLUSION: From
      1989 to 2000, the weight average of this population increased from 55.4 kg to
      59.1 kg. The medium of the increasing rate was 0.33 kg/y. The prevalence of
      overweight has increased dramatically from 9.0% to 23.2% from 1989 to 2000.
      Assuming that each kilogram of body weight gained represents 32284.6 kJ. We
      estimated that the medium of the excess energy accumulation was 29.3 kJ/d and the
      90th percentile was 94.2 kJ/d. Moreover energy derived from mixed composition
      diets is stored with an efficiency of at least 50% for nearly everyone. So we can
      estimated the energy gap should be 188.3 kJ/d. This estimate suggests that the
      behavior change needed to close the energy gap may be small and achievable
      without drastically altering current life-styles. For example, intaking 2%-3%
      less of the energy everyday or walk 10 minutes could offset weight gain in about
      90% of the population.

PMID- 16598942
TI  - [Effects of iron deficiency anemia on immunity and infectious disease in pregnant
      women].
AB  - OBJECTIVE: To review the changes in immune function and incidence of infectious
      diseases in pregnant women with iron deficiency anemia (IDA), especially
      marginalde-ficiency of iron. METHODS: T lymphocyte subsets level (CD3+, CD4+ and
      CD8+), nature kill cells activity (CD16), interleukin-2 (IL-2) and serum IgA,
      IgG, IgM and complement C3 were determined in 3 different wormen groups,
      including 69 IDA pregnant women who were diagnosed by Hemoglobin, concentrations
      of free erythocyte porphrin and serum ferritin from 280 pregnant women during 30
      38weeka of gestation, 52 random sampling normal pregnant women and 50 no pregnant
      women examined before marriage. RESULTS: The prevalenoe of IDA for pregnant women
      is 24.6%. The average concentration of Hb for pregnant women of IDA is
      102.00(6.00 g/L The level of CD3+ and CD4+ cells, the ratio of CD4+/CD8+ cells,
      serum IL-2 as well as IgG levels in the pregnant women were significantly lower
      than that of those normal pregnant women (P < 0.01, P < 0.05, P < 0.05, P <
      0.01). With the decreasing extent of Hb, these significant immunological indices
      of pregnant women will degrease. The incidence of infectious diseases in IDA
      pregnant women was significantly higher than that in normal pregnant women (P <
      0.05). CONCLUSION: There are significantly effects of IDA on cellular immune
      function and infectious disease during pregnancy. The study on effects of IDA
      during pregnancy on nature kill cells activity (CD16) and incidence of infectious
      diseases during puerperium should be continued by increasing sample's number.

PMID- 16598943
TI  - [Nutrition and feeding situation of Chinese 0- 5 years old infants and children
      in 8 provinces, cities and villages in 2004].
AB  - OBJECTIVE: To investigate and analyze present nutrition and feeding situation of
      0 - 5 years old infants and children in Chinese cities and villages and to
      understand main problems existed during Chinese infants and children's develop
      growing period in order to provide a basis for further drafting measures of
      nutrition amelioration. METHODS: To utilize an "Investigation to Nutrition
      Situation of 0 - 5 Years Old Infants & Children" which is opened in Chinese 8
      provinces, cities and villages in 2004 by Social Women Dept. of Ministry of
      Public Health, P. R. China to proceed measurement of height and body weight for
      17081 infants and children of 0 - 5 years of age in 8 provinces, cities and
      villages, also with Questionnaire form to proceed an investigation to parents of
      above said infants and children about their feeding situation. RESULTS: The
      develop-growing difference between cities and villages' infants and children
      appears to begin in April, a high occurrence period for 1 - 2 years old infants
      and children in villages with long period chronicle malnutrition as main cause
      that Chinese western area villages' nutrition rate is 20% above to be higher than
      Chinese middle and eastern areas. Infants and children's mother milk feeding rate
      is higher than whole nation's children nutrition monitoring result in 2000 with
      villages obviously higher than cities. In adding infants' supplementary foods
      there obviously existed unscientific and unreasonable problem of adding time,
      adding quality and quantity of supplementary foods. To analyze cause it is
      besides economic factors there existed obvious relation with shortage of
      knowledge in nutrition and health care by infants and children's parents.

PMID- 16598945
TI  - [Evaluation on quitting intervention in health professionals of six cities].
AB  - OBJECTIVE: To evaluate the impact of quitting intervention in health
      professionals of six cities, developing smoking cessation models in China.
      METHODS: All community directors and health professionals in Seven communities
      were selected in six cities of Beijing, Shanghai, Tianjin, Changsha, Shenzhen and
      Puyang were surveyed for smoking cessation using cross-sectional study. RESULTS:
      There were 25 hospitals that kept on providing smoking cessation service after
      the intervention. The percent of the awareness about "the harm of smoking is
      public health problem" has improved 12.8%. The percent of getting some smoking
      cessation methods and actively providing smoking cessation have improved 9.2% and
      7.3% respectively. CONCLUSION: Training the health professionals can not only
      increase their knowledge but also provide them smoking cessation service
      actively. It is a effective way to obtain methods and skills of quitting.

PMID- 16598944
TI  - [Logistic regression of the environmental risk factors in areas with Kashin-Beck
      disease].
AB  - OBJECTIVE: In order to find the factors influencing the prevalence of KBD, the
      possible nosogenetic factors of the family in Kashin-Beck disease (KBD) areas
      were analyzed. METHODS: The possible nosogenetic factors in mild, middle, high
      prevalence KBD areas were analyzed by logistic regression. The differences of the
      factors between three kinds of KBD areas were compared. RESULTS: Univariate
      analysis found sanitary conditions and meat-egg-mild were associated with KBD
      prevalence in all kinds KBD areas. Binary logistic analysis of multivariate
      suggested the possible nosogenetic factors were different in the different kind
      of KBD areas. It was wheat in mild prevalence area, sanitary conditions and meat
      egg-mild in middle prevalence area, and sanitary conditions, rice and meat-egg
      mild in high prevalence area. CONCLUSION: The risk factors are associated with
      the kind of KBD areas. The different preventive methods should be taken according
      to the kind of KBD areas, which will improve the effect of prevention.

PMID- 16598946
TI  - [Determination of chlorophenols in drinking water by headspace solid phase
      microextraction and gas chromatography].
AB  - OBJECTIVE: To study the method for determination of chlorophenols in drinking
      water by headspace solid phase microextraction and gas chromatography. METHODS:
      Chlorophenols in water samples was extracted using optimized SPME technology,
      separated by HP-5 chromatigraphic column and the concentration of chlorophenols
      was determined by electron capture detector (ECD). RESULTS: The detection limit
      of MCP, DCP, TCP, PCP were 60.0 microg/L, 2.64 microg/L, 0.15 microg/L and 0.84
      microg/L. The correlation coefficient(r) were 0.999, 0.997, 0.997, 0.995. When
      adding standard material of MCP, DCP, TCP, PCP at low, middle, high
      concentrations, the recovery rates were 95.3% - 107%, 93.6% - 102%, 92.4% - 102%,
      91.5% -99.1% and the RSD (n = 6) were 1.0% - 8.1%,1.6% - 6.6%, 2.9% - 8.6%, 2.0% 
      8.2%. CONCLUSION: The method was simple, sensitive and without solvent, which
      was an ideal method for determination of chlorophenols in drinking water.

PMID- 16598947
TI  - [Determination of selenium in selenium-enriched foods by hydride generation
      atomic absorption spectrometry].
AB  - OBJECTIVE: To determine selenium (Se) in selenium-enriched foods by hydride
      generation atomic absorption spectrometry. METHODS: The samples were digested by
      HNO3-HCLO4 and reduced by NaHB4, and then was determined in 6 mol/L HCL. RESULTS:
      The results showed that the detectable range, detection limit, recovery rate, and
      the relative standard deviation(RSD) of the method were 0 - 80.0 microg/L, 0.0056
      mg/kg, 92.05% - 103.88%, and 1.34% - 3.81% respectively. CONCLUSION: This method
      is suitable for selenium determination.

PMID- 16598948
TI  - [Effects of taurine and zinc on activity of NOS and expression of nNOS in
      cerebral cortex of acute hypoxic mice].
AB  - OBJECTIVE: To explore the effect of taurine and zinc on vigor of nitric oxide
      synthase (NOS) and the expression level of neuronal nitric oxide synthase (nNOS)
      in the cerebral cortex of acute hypoxic mice and the their neuroprotective
      effects. METHODS: Model of acute hypoxic mice was duplicated, NADPH-d
      histochemistry and nNOS immunohistochemistry were used to investigate the changes
      of NOS in different groups. RESULTS: Compared with the NS group, the anoxia
      endurance of the zinc sulfate group was increased 33.06%, while that of the
      taurine and zinc sulfate group was increased 26.83% than that of the zinc sulfate
      group (P < 0.05). Compared with the NS group, the number of NADPH-d positive
      neurons and nNOS positive neurons in cerebral cortex of zinc sulfate group were
      significantly decreased, while those of the taurine and zinc sulfate group were
      significantly decreased than the zinc sulfate group (P < 0.05). CONCLUSION: Both
      taurine and zinc could prolong the anoxia endurance, perhaps they might play an
      important role in decreasing the level of nitric oxide synthase to protect the
      brain against hypoxic damage.

PMID- 16598949
TI  - [Study on immunorepressive mice model by gamma irradiation].
AB  - OBJECTIVE: To establish the immunorepressive mice model by irradiation. METHODS:
      The 90 Kunming mice which the weight is from 30 to 34g were treated with 3Gy,
      4Gy, 5Gy gamma irradiation, the delayed allergy testing, the serum haemolysin
      level testing, the phagocytosing functions testing and the NK cell activity
      testing were performed at 3th, 7th, 14th, 21th days after irradiation
      respectively. RESULTS AND CONCLUSION: (1) All 3Gy, 4Gy, 5Gy gamma irradiation can
      cause mice immunorepressivestate except the NK cell activity. (2) The time of
      comeback after irradiation is different from immunity items. The serum haemolysin
      level is most sensitivity in all, but it comeback most slowly after irradiation.
      The phagocytosing functions comeback most rapidly after irradiation. (3) It
      suggests that the irradiation immunorepressive mice model can be established
      using it in order to evaluate the enhanceing immune function, assisting
      irradiation hazard protection function and alleviating toxicity function of
      irradiation treatment and chemical treatment. (4) The NK cell activity is not
      suitably to immunorespressive by gamma irradiation.

PMID- 16598950
TI  - [Capillary zone electrophoretic determination of NaFeEDTA in iron fortified soy
      sauce].
AB  - OBJECTIVE: An analytical method for separation and determination of sodium iron
      (III) ethylenediaminetetraacetate (NaFeEDTA) in iron fortified soy sauce by
      capillary zone electrophoresis (CZE) has been developed. METHODS: The
      electrolyte, which contains 30 mmol/L citric acid, 20 mmol/L Tris, 0.15 mmol/L
      CTAB and 0.05 mmol/L SDS, was used to improve the peak shape and reduce the
      retention time at the voltage of - 25.0 kV. The sample can be determined at UV
      254 nm after diluted. RESULTS: In this method, which enjoyed a wide linear range
      and good precision, the RSD (n = 6) was 2.15%, the average recoveries for samples
      ranged from 94.3% - 101.2% and the detection limit of the NaFeEDTA in iron
      fortified soy sauce is 4 microg/ml (S/N = 3). CONCLUSION: The results of
      application of different kinds of soy sauce showed that the method was direct,
      accurate, fast and simple.

PMID- 16598951
TI  - [Effect of excessive iodine exposure on the serum TC and TG level in rats].
AB  - OBJECTIVE: To study effect of excessive iodine exposure on the serum TC and TG
      level in rate. METHODS: According to body weight, 60 Wistar rats were divided
      into 6 groups and given drinking water including different doses of iodine. The
      iodine concentrations were 0 (control), 1800, 3600, 7200, 14000 and 28000
      microg/L, respectively. Three months later, related indices were determined.
      RESULTS: In excessive iodine groups, no obvious changes of thyroid morphology was
      observed. Urinary iodine level increased dose-dependently. Excessive iodine
      intake resulted in a significant reduce of serum TT4 level and an obvious
      increase of serum TC level in a dose-dependent manner. The positive correlation
      was observed between serum TC and urinary iodine. There was the negative
      correlation between serum TC and serum T4. CONCLUSION: Excessive-iodine exposure
      resulted in an increase in serum TC level. And serum lipids, together with
      urinary iodine and serum thyroid hormones, could be used as biomarkers for
      excessive iodine exposure.

PMID- 16598952
TI  - [Study on the development of DNA immunization technique].
AB  - As the third generation of vaccine, DNA immunization seems to be advantageous
      over classic immunization with purified proteins, which can induce complete
      immune responses against a number of infectious agents and can be used safely,
      economically and conveniently. The author reviews the new development of DNA
      immunization, including parameters affecting its effectiveness, the basic
      underlying biological mechanisms, and its application on generation of
      antibodies, infant immunization, mucous membrane immunization, and expression
      library immunization etc. In addition, we introduce some strategies of improving
      the effect of DNA immunization.

PMID- 16598953
TI  - [Recent advances for research on anti-tumor effects of TNF-related apoptosis
      inducing ligand].
AB  - Tumor necrosis factor (TNF)-related apoptosis--inducing ligand (TRAIL) is a
      member of TNF family. TRAIL selectively induces apoptosis in a wide variety of
      tumor cells, but not most normal cells through binding to its receptors. The
      ability of TRAIL to induce apoptosis in a large number of tumors has stimulated
      interest in TRAIL as a tumor therapeutic agent.

PMID- 16598954
TI  - [Toxicological study of fresh water microcystins].
AB  - Microcystins are a group of toxins that are produced by fresh water
      cyanobacteria. They are bioactive materials which are hepatotoxic. They can
      inhibit serine/threonine protein phosphatase (PP1 and PP2A), breaking the balance
      between protein phosporylation and phosphorylysis. They present a wide range of
      harmful effects to human body, such as hepatotoxicity and tumor promotion. They
      also affect other organs like kidney and intestines. Recently, more and more
      attention is being paid to microcystins worldwide. This review summarizes the
      progress in the toxicological study of fresh water microcystins.

PMID- 16598955
TI  - [Study on maximum limits for Salmonella in milk and milk products].
AB  - At present, the Chinese microbiological maximum levels for foods are different
      from several countries of the world. As China joined in the WTO, such levels, on
      the one hand, are not helpful for quality control and the protection for health,
      on the other, they are also not benefit to the export. To give information for
      revising the Chinese microbiological maximum levels for foods, this article took
      example for the Salmonella maximum levels in milk and milk products and all
      factors associated with their establishment were reviewed.

PMID- 16598956
TI  - [Chemical basis of the effects of Tamm-Horsfall protein on the formation of
      calcium oxalate stones].
AB  - Tamm-Horsfall (TH) protein is the most abundant protein in human urine. It plays
      dual roles in the formation of calcium oxalate stones depending on its structure,
      concentration and urine properties. In this paper, the chemical basis of the
      effects of TH protein on the formation of calcium oxalate stones was
      systematically discussed in view of the concentration of TH protein, the urinary
      pH, ionic strength, metallic ions, the cooperative effect of citrate and TH
      protein, and the effect on the adhesion of calcium oxalate crystals to the renal
      cell membrane. The differentiation between TH protein and its analog was also
      comparatively discussed.

PMID- 16598957
TI  - [Treatment of acute mania].

PMID- 16598958
TI  - [Homicide by mentally ill: clinical and criminological analysis].
AB  - The present study analysed the characteristics of homicide in internees according
      to the Social Defence system in Belgium. The Social Defence system was
      inaugurated in 1930, following the ideas of Adolphe Prins, a Belgian specialist
      in the criminal law. The Social Defence system concerns those offenders who are
      considered as mentally ill at large. The concept of mental illness encompasses
      the classical notion of "dementia" but also those people with mental unbalance as
      personality disordered offenders and mentally retarded persons. In the present
      study, we considered all those internees who committed a homicide or a homicide
      attempt and whose cases were examined by the review board between September 1998
      and June 2000. We collected 99 cases and studied the age at the time of the
      offence (mean: 32.2 years), their diagnoses, the status of victims. These 99
      murderers committed 111 "facts", a fact being a murder or murder attempt on one
      or several person(s) without arrest between the different phases of the
      commitment. These facts provoked 132 victims (72 men and 60 women); 61.36 %
      deceased. There was no significant difference in the characteristics of homicide
      versus homicide attempt. The results showed that, in our population, 59.6 % of
      the patients endorsed a diagnosis of psychosis (37 cases of paranoid
      schizophrenia, 2 schizophrenias of other types, 7 schizo-affective disorders, 1
      autistic disorder, and 12 delusional disorders). Other axis I disorders were 3
      intermittent explosive disorders, 2 major depressive disorders, 2 paraphilias and
      1 bipolar disorder. The 32 offenders with no axis I major mental diseases
      presented such diagnoses, alone or comorbid, as antisocial personality disorder
      (n = 17), borderline personality disorder (n = 8), paranoid personality disorder
      (n = 4), and schizoid personality disorder (n = 2), 14 were mentally retarded and
      5 presented a cerebral damage or an epilepsy. The age of the offender at the
      first homicide was not significantly different between the different diagnoses:
      group 1 : schizophrenia-type group (29.63 years) ; group 2 : comorbid diagnoses
      of schizophrenia and cluster B personality disorder (31.64 years) ; group 3 :
      cluster B personality disordered people (without psychosis) (27.90 years) ; and
      group 4 : the mixed group of residual diagnoses (32.63 years). Only the persons
      with a delusional disorder (group 5) significantly committed their homicide at an
      older age (47,06 year). We found no significant differences between group 2
      (54.55 %), 3 (69.23 %), and 4 (50 %) in the proportion of offenders having
      substance problems. The group 1 (schizophrenia-type without comorbid personality
      disorder) presented significantly less problems with substances (13.83 %) than
      the three former groups. The group 5 (20.0 % prevalence) exhibited only a
      significant difference with group 3. We distinguished instrumental and emotional
      violence. Instrumental violence was more represented in the facts committed by
      group 2, 3 and 4 versus group 5. Group 1 differed also significantly from groups
      2 and 3. The status of the victim(s) was divided in: 1) members of the family; 2)
      specifically known persons (outside the family); 3) specifically chosen victims
      (chosen, searched or followed because of their status, gender, profession, social
      role); 4) opportunity victims (victims present at the time and having sufficient
      characteristics to be attacked, e.g. being a woman, suspected to have some
      money); and 5) accidental victims. We demonstrated in our sample that victims of
      murderers in their family or specifically known were more frequently victims of
      pure psychotic offenders (groups 1 + 5) than of offenders of the mixed group
      (groups 2, 3 and 4) (21.97% vs 10.61%; 16,67% vs 13.64 %, respectively). On the
      contrary, specifically chosen (2.27 % vs 8.33 %) and opportunity victims (3.03 %
      vs 11.36 %) were more frequently attacked by the "mixed group". Accidental
      murders were almost only committed by psychotics (10.61 % vs 0.76 %), often in
      the context of a spree murder. In conclusion, we discuss that, from such a biased
      sample, the interest resides in the study of the comparison of the homicidal
      behaviour between psychotics (schizophrenia-type or delusional disordered),
      "mixed" and non-psychotics in terms of age at murder (older in delusional
      disorder), substance problems (more problems in non-psychotics), motivation (more
      emotional offences in psychotics) and statutes of victims (more family and known
      victims in psychotics). We are encouraged to precise our data on a larger sample
      and a longer period in future studies.

PMID- 16598959
TI  - [Relapse prevention group therapy for paedophiles: French adaptation].
AB  - Psychotherapy for sex offenders has only very recently started to develop in
      France. The French law on compulsory treatment for sex offenders was voted in
      1998, and many mental health practitioners are not trained to treat such patients
      yet. In our ambulatory forensic consultation, sex offenders have been treated
      since 1992 and group psychotherapy has been offered to them since 1994. Our first
      therapeutic models were the North-American behavioural-cognitive therapy and
      Pithers' relapse prevention model. Behavioural-cognitive theory describes
      paedophilia as an acquired sexual preference maintained by positive
      reinforcement. Pithers (1990) considered that relapse only occurs in high-risk
      situations, and that high-risk situations always come after offence precursors.
      In North America, relapse prevention consists in helping paedophiles spot their
      high-risk situations and offence precursors, and enhance their skills to cope
      with such situations or to prevent them. Therapy programs were developed
      according to these models, aiming to help offenders develop such skills, ie
      empathy, social skills, cognitive restructuring, self-esteem, etc. Trying to
      apply these therapy programs in France, our team quickly realised that we would
      have to adapt them to French culture. On the one hand, behavioural-cognitive
      theory did not seem satisfactory enough in explaining paedophilic behaviour and
      paedophilic preference. On the other hand, behavioural-cognitive therapy made
      patients into children too much and increased resistance. Therapy based on
      programs seemed too rigid for French patients and therapists, and we often felt
      we were working on an issue that would have been much more accurate to work on a
      few sessions earlier, when this issue was spontaneously brought up by a patient.
      We believe change occurs all the more as issues are worked on at the right moment
      for the patient. Moreover, on a cultural point of view, we also realised the use
      of programs in psychotherapy was difficult to accept in France both by patients
      and therapists, as our culture is strongly influenced by psychoanalysis,
      especially free association. The use of a plethysmograph was also impossible in
      our country. We thus decided to use Pithers' relapse prevention model but to let
      our patients free to speak, so our therapy was not a program. Offences were
      analysed according to Pithers' ideas about high-risk situations and offence
      precursors. Most of the sessions were non-directive, but therapists offered each
      patient to work on his offence when they believed it was the right moment.
      Important issues (such as empathy, cognitive distortions, emotional control,
      etc.), were tackled as they came up, which seemed easier and less rigid as
      sessions were linked to patients' current pre- occupations. Post-group meetings
      enabled therapists to draw themes that seemed important to work on with each
      patient (empathy, consequences on victims, anger, cognitive distortions,
      emotional expression, relational issues, self-esteem, intimacy...). These issues
      were discussed the next time they were raised by the group. We were interested to
      notice that all important issues came up spontaneously from the group during the
      sessions as long as patients were free to share their concerns, without
      therapists having to set issues beforehand. Two case studies illustrate our
      method. Bernard was 40 when he first came to our consultation. Originally a
      teacher, he was dismissed and became a marketing man after being sentenced to
      five years of prison for sex offences on two 6-year-old girls. Bernard relapsed a
      few years after he got out of prison by sexually offending two girls, aged 10 and
      13. At our first interview, Bernard had cognitive distortions about sexual
      education and always avoided sexually explicit words to describe the offences. He
      did not realise the consequences of his acts on the victims, but said he wanted
      to be treated because he felt lonely. He first described a sexual preference for
      adult women, but progressively aknoledged feeling attracted to female teenagers.
      He did not know why the offences occurred at such a moment in his life, and had
      no idea of his high-risk situations nor of his offence precursors. Bernard often
      confused his need for sex and his need for affection. After four years'
      participation to our relapse prevention group therapy, Bernard has clarified his
      sexual preferences : he has always been mostly attracted to girls from 6 to 10
      years old. He has also always been attracted to women younger than him, and now
      seems to be mostly aroused by female teenagers. Working on his offences has
      helped him identify his high-risk situations and the strategies he used to get
      close to his victims and to be trusted by them and their single mothers. Bernard
      often offended when he was feeling lonely and rejected, after a break-up with a
      partner. Twice during these four years, Bernard found himself in such high-risk
      situations, but managed to stop before relapsing. However, empathy towards
      victims is still difficult to develop for Bernard. Neither has he yet managed to
      build a new relationship with a woman, as he still seems to suffer from an
      unhappy love affair he went through several years ago. This case study shows one
      of the limits of Pithers' relapse prevention model, if it is used mechanically.
      Indeed, we should logically have spotted as high-risk situations for Bernard
      interactions with 6 to 10 year-old girls. Helping him face his past and present
      sexual fantasies led Bernard realise his high-risk situations were now mainly
      about teenage girls, even if he had mostly been attracted to younger girls
      earlier in his life. After 2 to 3 years of therapy, we have quite often noticed
      this kind of evolution in sexual preferences in paedophiles, their preferences
      changing towards teenagers or young adults. In France, mental health
      professionals are often reluctant to follow sex offenders because of negative
      counter-transference and lack of specific training. However, first changes often
      occur quite quickly in paedophiles when they are offered group therapy. The group
      makes it easier to confront paedophiles to the reality of their offence and of
      their sexual fantasies. These patients often express being very relieved after
      the first sessions, as the group therapy is generally their first opportunity to
      express their feelings, sexual fantasies and thoughts about paedophilia. Pithers'
      model, used within a group were patients are free to speak in a human, warm and
      confronting atmosphere, seems clinically accurate and effective in helping
      paedophiles in France. We now need studies to check therapy effectiveness on
      relapse and to understand which therapy factors are efficient on sex offenders.

PMID- 16598960
TI  - [A new patient focused scale for measuring quality of life in schizophrenic
      patients: the Schizophrenia Quality of Life Scale (SOL)].
AB  - RATIONALE/OBJECTIVE: Quality of Life (QOL) has been recognized as an important
      measure of the outcome of patients by clinicians and policy makers in Mental
      Health. The emerging consensus in the health field that personal values and the
      patient's preferences are important in monitoring the quality of medical care
      outcomes makes it even more important to assess the patient's perspectives.
      Unfortunately, there is little consensus about what constitutes QOL or how to
      measure it, particularly in psychotic patients. The objective of this study is to
      report the stages of development and validation of a QOL questionnaire based on
      issues pertinent to patients with schizophrenia. METHOD: During a first phase,
      identical pattern were identified among interviews (conducted by psychologists)
      of schizophrenic patients (DSM IV, n = 100), mental health staff (n = 20) and
      families (n = 20). The data gathered in the first phase were discussed and
      organized, by 25 experts, into a structure that made up the skeleton of the scale
      (133 items, 17 factors). Based on a prospective epidemiological study conducted
      with 337 French psychiatrists, a validation analysis of structural and
      psychometric proprieties was performed. Finally reliability of the scale was
      assessed by a second test/retest (D0, D7) study (n = 100). RESULTS: A total of
      686 schizophrenic, schizophreniform or schizoaffective patients (DSM IV) were
      included. Internal consistency analysis identified 14 factors (74 items), all
      with a Cronbach's alpha of at least 0.75: professional life (0.95), affective and
      sexual life (0.92), illness knowledge (0.90), relationship (0.92), life
      satisfaction, (0.87), coping with drugs (0.79), drugs impact on the body (0.87),
      daily life (0.83), family relationship (0.81), future (0.88), security feeling
      (0.84), leisure (0.87), money management (0.76) and autonomy (0.75). Construct
      validity was confirmed (Pearson test) using established clinical (Brief
      Psychiatry Rating Scale and Clinical Global Improvement), social (Psychological
      Aptitude Rating Scale) and generic quality of life (Functional Status
      questionnaire) measures, correlation coefficient was significant for all factors
      but 2 in the BPRS (illness knowledge and coping with drugs) and 3 in the CGI
      (illness knowledge, coping with drugs and life satisfaction). Lastly, test/retest
      indicated high reliability for each factor (p < 0.001), the lower correlation
      coefficient (r) was 0.526. CONCLUSIONS: The Schizophrenia Quality Of Life-scale
      (SOL), based on a patient's point of view approach, is an efficient,
      multidimensional instrument designed for the measurement of the consequences of
      schizophrenia on individuals' lives.

PMID- 16598961
TI  - [Management of suicidal adolescents: a clinical audit in 76 hospitals].
AB  - We describe the implementation and results of a clinical audit of the management
      of suicidal adolescents in hospital that was carried out as part of the French
      national suicide prevention programme. The ANAES definition of a clinical audit
      is: "an assessment method using defined criteria that compares care practices
      with accepted standards and measures the quality of these practices and the
      results of care with a view to improving them". Standards for the audit were
      derived from the clinical practice guidelines published by ANAES (French National
      Agency for Accreditation and Evaluation in Health) in November 1998. They
      comprised 15 criteria covering ressources available and procedures implemented:
      patient management in hospital (9 criteria), contacts made with the patient's
      environment outside hospital (2 criteria) and preparation for discharge from
      hospital (4 criteria). Participation in the audit was voluntary. Overall, 76
      hospitals from the 10 regions of France with a suicide prevention programme took
      part in the audit and made 1,554 observations. The number of observations per
      hospital ranged from 1 to 42. Compliance with the criteria was > 80 % for 5
      criteria, 50-80 % for 3 criteria, and < 50 % for 7 criteria. A total of 26
      hospitals, proposed a structured improvement plan, ie, scheduled, ordered and
      ranked measures with a definition of responsibilities and follow-up. Of these 26
      hospitals, 15 had implemented the three ANAES recommendations (setting up a
      working group for the project, using a grid to analyse results, drafting a
      structured report) whereas only 5 of the 50 hospitals that did not come up with
      an improvement plan had done so. An operational outcome thus seems related to
      compliance with the audit method. Three years after the audit was set up, 17
      hospitals took part in a second round. Improvements were noted for 12 criteria,
      mainly for those giving poor results in the first round. However, these
      improvements concerned few hospitals (eg just 4 hospitals for the criterion with
      the worst result in the first round). A worsening of compliance was noted for 3
      criteria. In conclusion, hospitals were found to comply with guidelines relating
      to the management of suicidal adolescents in hospital. However, compliance with
      guidelines relating to making contact with the patient's environment outside
      hospital and preparing for discharge was less good. Although the hospitals taking
      part in the audit endorsed our method, our experience showed that, to be
      effective, clinical audits need methodological support and a well-defined time
      schedule.

PMID- 16598962
TI  - [Comorbidity between eating disorders and mood disorders: review].
AB  - OBJECTIVE: Comorbidity between eating disorders (ED) and mood disorders is a
      major issue when evaluating and treating patients with anorexia nervosa (AN) or
      bulimia nervosa (BN). In the literature, estimated comorbidity rates of mood
      disorders in subjects with ED differ widely across studies. Obviously, it is
      difficult to compare results from various sources because of differences in
      methods of assessment of depressive symptoms and in diagnostic criteria for both
      ED and mood disorders. Furthermore, few studies have included control groups,
      and, since mood disorders are among the most frequent psychiatric disorders in
      women--with an average estimated lifetime prevalence of 23.9 % (Kessleret al.,
      1994)--, it is not clear, yet, whether mood disorders are more common among women
      with an ED (AN or BN) than among women from the community. The only review
      articles we found on the relationships between ED and mood disorders survey
      different types of arguments in favour of a link between both categories of
      disorders, including symptoms, personal and family comorbidity, overlap in
      biological findings, and treatment results, but do not review in detail available
      comorbidity data. The aim of this paper is to conduct a critical literature
      review on studies assessing the prevalence of mood disorders in subjects with an
      ED (AN or BN). In the first part, we will discuss methodological issues relevant
      to comorbidity studies between ED and mood disorders, and select the most
      reliable studies. In the second part, taking into account these methodological
      considerations raised, we summarize the findings of these studies. METHOD: We
      performed a manual and computerized search (Medline) for all published studies on
      comorbidity between ED and AD, limiting our search to the 1985-2002 period, in
      order to get sufficiently homogeneous diagnostic criteria for both categories of
      disorders. RESULTS: Too few studies include control groups and few studies have
      compared diagnostic subgroups of ED subjects, with scarce or conflicting results.
      DISCUSSION: We reviewed numerous studies here and conclude simply that there are
      many arguments in favor of elevated rates of MD in ED subjects, but there is no
      convincing evidence yet. Many questions are left unanswered or have conflicting
      responses. Our review highlights the need for further studies, which should
      address several requisites: comorbidity studies should be designed with this as a
      specific goal, rather than as a secondary aim within other types of studies (such
      as treatment studies, follow-up studies, etc.). Kendler et al. (1991) state that
      individuals with two disorders are more likely to present for treatment than
      individuals with one, therefore, comorbidity rates (which are not in agreement
      with a special etiologic relationship between BN and depression) may be
      exaggerated in clinical population results. New studies should include control
      subjects, matched (at least) for sex and age with ED subjects. Studies should
      evaluate prevalence of all types of MD in order to yield comparable estimates of
      MD in general. Comorbidity studies should be conducted on both current and
      recovered patients, compared to subjects from the community. It is still
      necessary to demonstrate specificity of findings, i.e. that early onset MD are of
      specific etiological importance to ED and do not simply increase the risk of
      later psychopathology in general. Studies should be conducted on larger samples,
      and all diagnostic subgroups should be considered (restrictive and bulimic
      anorexics, bulimics with and without history of AN, with or without purging).
      Multivariate comparisons should be performed, taking into account subject age,
      sex (if men are included), in- and outpatient status, course of illness, and
      other possibly relevant variables. Thus, more reliable estimates of the frequency
      of MD in subjects with ED could provide us with valuable etiologic, therapeutic
      and prognostic information.

PMID- 16598963
TI  - [Perceptive and semantic selection difficulties and cognitive aging].
AB  - This work took place within tipper's negative priming paradigm. In a study with
      two age groups (young and older adults), Connelly and Hasher have measured the
      identity negative priming, the location negative priming and the "identity and
      location" negative priming. They used a simple material (letters). For these
      authors, the young people showed the negative priming effect in all the
      conditions, but the older people showed this effect only in location and in
      "identity and location" conditions, but there was no effect in identity
      condition. Hence, there is a dissociation between identity and location in the
      older adults group. Our work replicated the procedure of Connelly and Hasher
      using material presenting semantic (words) and perceptive selection difficulties.
      Our results were not consistent with the results of the authors. For the two age
      groups, the "location" and "identity and location" conditions were computed
      statistically faster than the "identity" condition, and there was no difference
      in the reaction times between the "location" and "identity and location"
      conditions. In the young adults group, even if an identity negative priming was
      obtained, there was no effect in the "location" and "identity and location"
      conditions (in comparison with a control condition). This led us to conclude is
      the existence of a dissociation between identity and location for the young
      adults. In the older adults group, we obtained positive priming in the "identity
      and location" condition, and no effect in the other conditions. Moreover, the
      reaction times in the "location" and "identity and location" conditions were
      faster than in the identity condition. We think about a dissociation between
      identity and location in the older group. Our data led us to conclude in the
      existence of a dissociation between identity and location, not only for the older
      adults, but also for the young adults. Our conclusion agrees with the
      explanations given by the authors regarding the neurological system; with the
      existence of two neuronal pathways, one for the identity and the other for the
      location. We explain the negative priming effect obtained in the young adults
      group through controlled inhibition processes, and we explain the positive
      priming obtained in the older adults group through automatic recuperation
      processes.

PMID- 16598964
TI  - [Self concept in falling and non-falling elderly].
AB  - The fall in elderly is frequent and implies great outcomes. Inhibition and
      turning on oneself mark the post-fall syndrome which illustrates perturbations
      from fall. This study compares the self concept of old persons with fall and
      without fall, self concept definited like the perceptions of a subject about
      himself. Words production is significatively less important for fall subjects and
      indicates the preponderance of the structure personal Self (SP). The auto
      description is negative with auto depreciatory, loss of confidence, decreasing of
      activities, feeling of helpessness in daily life and in future.

PMID- 16598966
TI  - [Mixed states in bipolar disorders: a review of current therapeutic strategies].
AB  - Mixed states are characterized by the mixture or rapid alternation, within hours,
      of manic and depressive symptoms. They bear a high suicidal risk and therefore
      represent a major therapeutic issue. We performed a computerized bibliographic
      search and reviewed the efficacy of the available treatments of mixed states. It
      confirmed the recognized poor efficacy of lithium and the need to discontinue
      antidepressants. Among mood stabilizers, divalproate and its derivatives are
      those with the highest level of evidence. As regards new anticonvulsants, the
      data are yet too limited to recommend them as first line treatments. They may
      however be used as second line or adjunct treatments in case a monotherapy with a
      reference treatment has failed. Among antipsychotic drugs, clozapine has
      demonstrated its efficacy but also remains a second line treatment due to its
      high risk of neutropenia and agranulocytosis. Electroconvulsive therapy is a
      useful alternative in treatment resistant cases or when there is an imminent risk
      for suicide. Some degree of uncertainty remains for the treatment of the so
      called "agitated depressions" as no study has yet focused on this issue with a
      specifically selected sample of patients. Such a study would also enlighten the
      uncertain nosological status of this clinical entity and would answer as to
      whether they belong to the category of mixed states.

PMID- 16598965
TI  - Pharmacokinetic profile of long-acting injectable risperidone at steady-state:
      comparison with oral administration.
AB  - The single dose pharmacokinetic profiles of long-acting injectable (LAI)
      risperidone and oral risperidone were extrapolated to steady-state. Plasma
      concentrations of the active moiety (unchanged risperidone + 9-hydroxy
      risperidone) were measured by radioimmunoassay up to 72 h after a single oral 1
      mg dose of risperidone in healthy volunteers (n = 12), and up to 84 days after a
      single intramuscular injection of 50 mg LAI risperidone in schizophrenic patients
      (n = 26). These data were projected to multiple dose regimens (4 mg/day for the
      oral formulation and 50 mg every 2 weeks for LAI formulation) using the software
      package WinNonlin, and average steady-state pharmacokinetic profiles were
      predicted. The most interesting results, obtained at steady-state, were a lower
      predicted peak plasma level (46 vs. 62 ng/ml) and a lower predicted degree of
      fluctuation between Cssmax and Cssmin (53 vs 145%) with LAI compared to oral
      administration, which is in line with actual steady state data on LAI
      risperidone. In conclusion, the pharmacokinetic profile of LAI risperidone
      administered every 2 weeks ensures a steady-state profile with concentrations
      falling in the interval observed with an equivalent oral dose but with lower and
      less fluctuations (i.e. 1/2 weeks vs 1/day).

PMID- 16598967
TI  - [Problematic family history of personality disorders].

PMID- 16598968
TI  - [Evolution of substance abuse in the beginning of schizophrenia in Quebec between
      1980 and 2004].

PMID- 16598969
TI  - [Visuospacial perception in working memory and cognitive disorganization among
      schizophrenics].

PMID- 16598971
TI  - What's your diagnosis? Waardenburg syndrome type I.

PMID- 16598970
TI  - Management of nasolacrimal duct obstruction: balloons, tubes, and timing.

PMID- 16598972
TI  - Fundus fluorescein angiography in retinopathy of prematurity.

PMID- 16598973
TI  - Probing for nasolacrimal duct obstruction using intranasal midazolam sedation as
      an alternative to general anesthesia.
AB  - OBJECTIVE: To investigate the effectiveness of topical anesthesia with sedation
      using intranasal midazolam in patients with symptomatic congenital nasolacrimal
      duct obstruction undergoing probing. PATIENTS AND METHODS: In this prospective
      study, probing was performed with general anesthesia (30 cases) and with topical
      anesthesia using intranasal midazolam (0.3 mg/kg; 44 cases) in 74 patients who
      were divided into two groups, those 6 to 36 months old and those older than 36
      months. The groups were compared after 12 to 48 months (mean, 18.2 months).
      RESULTS: For the patients 6 to 36 months old, the success rate was 80% in the
      group who received general anesthesia and 88.9% in the group who received topical
      anesthesia with intranasal midazolam; the difference between the two groups was
      not statistically significant (P > .05). For the patients older than 36 months,
      the success rate was 20% in the group who received general anesthesia and 25% in
      the group who received topical anesthesia with intranasal midazolam; there was no
      statistically significant difference between the two groups (P > .05).
      CONCLUSIONS: Probing with topical anesthesia in the office setting is usually
      recommended for patients younger than 8 months. Our results show that this is
      suitable for children until 4 years of age with the support of intranasal
      midazolam sedation. Probing under topical anesthesia with intranasal midazolam is
      cost-effective, safe, and comparable in efficacy to probing under general
      anesthesia but with less risk.

PMID- 16598974
TI  - Fundus fluorescein angiography in the screening for and management of retinopathy
      of prematurity.
AB  - OBJECTIVES: To describe the characteristics of fundus fluorescein angiography in
      retinopathy of prematurity (ROP) and to explore the possible benefits of fundus
      fluorescein angiography over conventional indirect ophthalmoscopy in the
      screening for and management of ROP. PATIENTS AND METHODS: Beginning in January
      2003, 23 consecutive patients were recruited for a nonrandomized, investigational
      trial. Fifty-one sessions of fundus fluorescein angiography were performed as
      part of ROP screening. RESULTS: Fundus fluorescein angiography caused no adverse
      effect. Clear angiograms were easily obtained. There was delayed arm-to-eye
      fluorescein transit. Leakage of fluorescein was observed in all stage 2 and stage
      3 ROP. The leakage resolved soon after treatment. Arteriovenous tufts were found
      far posterior to the ROP ridge and were a feature of severe ROP. CONCLUSIONS:
      Some vascular pathology observed on angiograms cannot be seen on indirect
      ophthalmoscopy. There was delayed arm-to-eye transit and fluorescein transit
      within the eyes. Fundus fluorescein angiography allows more objective assessment
      of disease stage and zone. Regression of ROP is clearly observed on fundus
      fluorescein angiography.

PMID- 16598975
TI  - Comparison of results of medial rectus muscle recession using augmentation, Faden
      procedure, and slanted recession in the treatment of high accommodative
      convergence/accommodation ratio esotropia.
AB  - BACKGROUND AND PURPOSE: According to the literature, accommodative esotropia has
      an unpredictable course when nonsurgical treatment is considered, especially in
      cases with a high accommodative convergence/accommodation ratio (AC/A). The aim
      of this study was to compare the results of augmented recession, slanted
      recession, and recession with posterior fixation suture of the medial rectus
      muscles in the treatment of high AC/A esotropia. SUBJECTS AND METHODS: Twenty
      eight children (4 to 14 years old) with high AC/A esotropia with a near-distance
      disparity greater than 10 PD were included in a prospective, randomized, blinded
      clinical trial. Nine children underwent recession of both medial rectus muscles
      and posterior fixation suture (Faden procedure), 9 children underwent augmented
      recession of the medial rectus muscles, and 10 children underwent slanted
      recession of both medial rectus muscles. The amount of esodeviation was measured
      before strabismus surgery and at least 6 months postoperatively. RESULTS: In the
      augmented recession group, the mean near-distance disparity was reduced from
      16.33 +/- 2.17 PD preoperatively to 7.55 +/- 3.87 PD postoperatively (54.21%; P =
      .056). In the Faden procedure group, it was reduced from 15.22 +/- 4.08 PD to
      2.55 +/- 4.03 PD (80.7%; P = .056). In the slanted recession group, it was
      reduced from 15.50 +/- 4.30 PD to 4.10 +/- 4.80 PD (67.55%; P = .056).
      CONCLUSIONS: The Faden procedure had the best outcome, but slanted recession also
      was successful. Because of our good results and an easy, non-invasive approach
      without any additional complications, we recommend slanted recession to treat
      high AC/A esotropia.

PMID- 16598976
TI  - Changes in corneal and conjunctival sensitivity, tear film stability, and tear
      secretion after strabismus surgery.
AB  - PURPOSE: Some patients complain of a foreign body sensation, a burning sensation,
      or dryness after strabismus surgery. We prospectively investigated the changes in
      corneal and conjunctival sensitivity, tear film stability, and tear secretion
      after strabismus surgery. PATIENTS AND METHODS: Corneal and conjunctival
      sensitivity were assessed with an esthesiometer, tear film breakup time was
      measured, and the Schirmer test was performed prospectively (preoperatively and 1
      week, 1 month, and 3 months postoperatively) in 83 patients (124 eyes) who
      underwent strabismus surgery at our institution. RESULTS: There were no
      significant changes in corneal sensitivity, tear film stability, or tear
      secretion after strabismus surgery (P > .05). Conjunctival sensitivity decreased
      significantly after strabismus surgery (P < .05). CONCLUSION: Discomfort and
      dryness after strabismus surgery do not seem to be related to changes in corneal
      sensitivity, tear film stability, or tear secretion.

PMID- 16598977
TI  - Better optic disc examination: wearing loupes enhances the indirect
      ophthalmoscope image.
AB  - Optic disc examination with the indirect ophthalmoscope is frequently used in the
      assessment of pediatric glaucoma cases. If the usual viewing eye-pieces are
      removed from the headgear and loupes worn instead, then a greatly magnified view
      of the disc is seen with little change to technique or ease of examination.

PMID- 16598978
TI  - Ocular manifestations of chromosome 14 terminal deletion.
AB  - A boy with chromosome 14 terminal (14q32.3) deletion presented with typical
      facial dysmorphism, mental retardation, and hypotonia. Ocular examination
      revealed esotropia, jerk nystagmus, microcornea, and retinal-choroidal colobomas.
      We report the first case of microcorneas and colobomas in association with
      chromosome 14 terminal deletion to help further define this clinical syndrome.

PMID- 16598979
TI  - Two cases of Goldenhar syndrome.
AB  - We describe two boys with Goldenhar syndrome. The 8-year-old boy had an epibulbar
      dermoid in his left eye, type 1 Duane syndrome, bilateral preauricular
      appendages, and an interauricular septal defect. The 10-year-old boy had an
      epibulbar dermoid in his right eye, appendages in the right preauricular region,
      and sensorineural hearing loss.

PMID- 16598980
TI  - Development of multiple subretinal hemorrhages during diode laser supplementation
      for retinopathy of prematurity.
AB  - A premature infant had subretinal hemorrhages in one eye after laser ablation for
      threshold retinopathy of prematurity. We postulate that subretinal hemorrhages
      occur from trauma to the microvasculature secondary to globe manipulation during
      scleral depression at the time of laser treatment.

PMID- 16598981
TI  - Pseudallescheria boydii keratitis.
AB  - We describe a patient with Pseudallescheria boydii keratitis. The treatment of
      mycotic keratitis remains difficult. This case demonstrates that identification
      and susceptibility testing should be rapidly performed. In cases of indolent
      keratitis, the possibility of fungal infection should be kept in mind.

PMID- 16598982
TI  - Unilateral clinical anophthalmia with optic nerve hypoplasia in the fellow eye.
AB  - We present the clinical and radiologic findings of two cases of clinical
      anophthalmia in one eye and optic nerve hypoplasia in the other eye. We propose
      possible causes of this rare finding.

PMID- 16598984
TI  - Images in pediatric ophthalmology. Marfan's syndrome.

PMID- 16598983
TI  - Atypical oculo-orbital complex choristoma in organoid nevus syndrome.
AB  - We report organoid nevus with left oculo-orbital choristoma fixing the globe in
      hypotropia, precanthal skin tag, and upper eyelid coloboma and right limbal
      dermoid. Computed tomography revealed a dilated lateral ventricle and cerebral
      atrophy. No neurologic deficit existed. The coloboma was repaired, choristoma
      debulked, and precanthal tag excised.

PMID- 16598985
TI  - Allergic rhinitis: managing the pediatric spectrum.
AB  - Allergic rhinitis (AR) is the most common chronic disease in the pediatric
      population and its prevalence is increasing. AR can significantly impact a
      child's health. It causes uncomfortable symptoms, impairs quality of life, and
      can predispose to the development of comorbidities such as asthma. Although
      allergen avoidance is the first step in AR management, it often is impractical.
      Fortunately, there are a number of pharmacologic agents available for the
      treatment of AR. When choosing a medication, attention should be paid to the
      substance's risk/benefit ratio. First-line therapy consists of second-generation
      antihistamines, which lack many of the unwanted side effects caused by first
      generation compounds, and intranasal corticosteroids, which are the preferred
      agents for children with persistent symptoms. Other pharmacologic options include
      decongestants, leukotriene-receptor antagonists, and intranasal cromolyn sodium.
      Allergen immunotherapy can be a valuable adjunctive modality. Issues of
      compliance and convenience also are important considerations.

PMID- 16598986
TI  - Allergic rhinitis: managing the adult spectrum.
AB  - With the general population increasing in age, clinicians will be seeing more
      elderly patients. Many present with bothersome rhinitis. A number of
      physiological and anatomic changes associated with age predispose the elderly
      population to develop rhinitis. A number of categories of rhinitis occur in
      elderly people and it is important to make the correct diagnosis. Appropriate
      therapy is available but the clinician must be wary of side effects, particularly
      to antihistamines and decongestants that may be more severe in elderly patients.

PMID- 16598987
TI  - Managing impairment in patients with allergic rhinitis.
AB  - Allergic rhinitis is a common medical problem in both the adult and the pediatric
      population. A main complication of this disease is a reduction in the patient's
      quality of life. Individuals with either seasonal or perennial allergic rhinitis
      often are impaired, adversely affecting work and/or school performance. This
      impairment can result from the disease itself and the treatment thereof. Oral
      antihistamines are the mainstay of treatment for allergic disease. First
      generation antihistamines are considered sedating and frequently are impairing
      even when sedation is absent. Second-generation antihistamines show some class
      variability regarding impairment but as a group are clearly less impairing than
      their first-generation predecessors. Second-generation antihistamines are the
      preferred medication when antihistamines are necessary.

PMID- 16598988
TI  - Chronic cough: an interactive case discussion.
AB  - The following case was presented at the Eastern Allergy Conference May 2005 to
      each of four small group sessions in an attempt to incorporate problem-based
      learning (PBL) into the curriculum of the conference for the first time in its 18
      year history. Before this, the format had always been non-stop lectures for four
      days. The attempt to use PBL in breakout sessions was due to the well-documented
      improved learning experience with PBL demonstrated by multiple studies in the
      literature of PBL for CME. This PBL case on an adult who presents with a "chronic
      cough" was linked to a series of three didactic lectures to reinforce the
      differential diagnoses in this patient. The three lectures followed the PBL
      breakout sessions (during the morning of the conference) and were entitled
      Laryngeal Pharyngeal Reflux (LPR), Chronic Sinusitis: A Surgical Perspective and
      Chronic Cough. Although the best learning scenario for this case occurs when
      there is interaction with one's peers, review of this case and answering the
      questions that were posed by the facilitators can still provide a great learning
      experience.

PMID- 16598989
TI  - Laryngopharyngeal reflux.
AB  - Laryngopharyngeal reflux (LPR) is the retrograde movement of gastric contents
      (acid and enzymes such as pepsin) into the laryngopharynx leading to symptoms
      referable to the larynx/hypopharynx. Typical LPR symptoms include dysphonia,
      globus pharyngeus, mild dysphagia, chronic cough, and nonproductive throat
      clearing. Most patients are relatively unaware of LPR with only 35% reporting
      heartburn. LPR has been associated with such disease entities as vocal fold
      granulomas and laryngospasm and is believed to play a role in the formation of
      subglottic stenosis. Although not yet substantiated, chronic laryngeal irritation
      may lead to the formation of laryngeal carcinoma in those patients without a
      history of alcohol consumption or tobacco smoking. Many issues with respect to
      the diagnosis and treatment of LPR are considered controversial, including the
      clinical diagnostic criteria and the studies necessary to establish a diagnosis.
      LPR, like other forms of extraesophageal manifestations of reflux, is treated
      with a combination of diet changes, behavior modifications, and a regimen of high
      dose, twice-a-day proton pump inhibitors. Allergists, as physicians who treat
      patients with chronic cough, globus sensation, and atypical asthma not responsive
      to medications, need to be familiar with the diagnosis and proper treatment of
      LPR to deliver optimal care to these patients.

PMID- 16598990
TI  - Chronic sinusitis: a surgical perspective.
AB  - Rhinosinusitis is one of the most common chronic diseases with significant
      symptoms and impact on the quality of life. Surgery is indicated when appropriate
      medical treatment fails. A review of the clinical presentations of rhinosinusitis
      is presented, as well as an overview of current medical and surgical treatment
      options. Although external approaches are still mandated in some selected
      instances, endoscopic sinus surgery has become the standard for surgical
      treatment of sinonasal pathologies, by aiming at restoring the physiological
      functions of the nasal and paranasal cavities. This technique presents numerous
      advantages with a minimally invasive approach, better visualization of
      structures, camera magnification of the surgical field, and allows thorough
      exploration of difficult-to-reach areas. The risks and complications of
      endoscopic sinus surgery are well identified and may be reduced significantly by
      the adjunct use of computer-assisted image guidance and intraoperative
      fluoroscopy. Surgical simulation also is a promising tool to help reduce surgical
      errors and improve surgeon training in the future.

PMID- 16598991
TI  - Gastroesophageal reflux disease and sinusitis: their role in patients with
      chronic cough.
AB  - The causes of coughing are multiple. Research into the physiology of coughing has
      established that interactions amid C-fibers and rapidly activating receptors in
      humans have the most significant effect on stimulation of coughing. Precipitants
      of coughing include gastroesophageal reflux and sinusitis. Stimulation of vagal
      afferents by esophageal irritation and aspiration of acidic gastric contents or
      vapors are the most frequently cited causes of cough associated with
      gastroesophageal reflux or laryngopharyngeal reflux. Sinusitis may precipitate
      coughing from other mechanisms including aspiration of postnasal drainage and
      sinopulmonary reflex. Taking a lesson on how these conditions affect asthmatic
      patients, this article will review how these two conditions may also influence
      cough in normal patients.

PMID- 16598992
TI  - The role of arterial blood gases, exercise testing, and cardiac examination in
      asthma.
AB  - The severity of bronchial asthma may not be assessed easily in some patients
      using the current evaluation methods. In this study, we aimed to obtain more
      objective and detailed data in evaluating patients with stable mild and moderate
      bronchial asthma and to validate the current parameters against more objective
      ones in determining the disease severity. One-hundred six stable patients with
      bronchial asthma were included in the study. These patients underwent spirometric
      and cardiological examination, 6-minute walk testing (6MWT) and arterial blood
      gas analysis. Continuous measurement of pulse oxymetry (SpO2) was done during
      6MWT. Dyspnea that developed during 6MWT was measured using the modified Borg
      category scale. Sixteen patients were found severely hypoxemic at rest, and 16
      patients were severely desaturated at 6MWT. Nineteen patients had pulmonary
      hypertension on echocardiography. Patients with oxygenation problems were older
      and had longer disease duration, lower forced expiratory flow of 25-75%, higher
      Borg exercise rating, and higher pulmonary artery pressure (p < 0.05). Patients
      with pulmonary hypertension had earlier disease onset, lower forced expiratory
      flow of 25-75%, lower arterial oxygen tension and lower pre-6MWT SpO2 (p < 0.05),
      older age, and lower SpO2 at 6MWT (p < 0.01). Classic evaluation methods
      correctly operated only on the two-thirds of asthmatic patients. Cardiological
      examination, 6MWT, and arterial blood gas analysis were needed for the true
      evaluation of other patients who had potentially progressive disease. We think
      that evaluation of asthmatic patients with these more objective and detailed
      methods provides important additional clinical data.

PMID- 16598993
TI  - The response to intravenous immunoglobulin replacement therapy in patients with
      asthma with specific antibody deficiency.
AB  - In a retrospective analysis of our patient population, 20 difficult-to-treat
      patients with asthma were found to have clinical and laboratory evidence of
      specific antibody deficiency, and several had mild hypogammaglobulinemia.
      Intravenous immunoglobulin replacement therapy at 400-600 mg/kg every 3-4 weeks
      gave remarkable clinical benefits, with reduction in morbidity, number of
      hospitalizations, steroid therapy, and number of respiratory infections. We
      believe that, in this group of patients, the use of intravenous immunoglobulin
      perhaps allows the achievement of asthma prevention rather than an amelioration
      of inflammation.

PMID- 16598994
TI  - Allergic rhinitis in Korean immigrants to the United States.
AB  - The prevalence of allergic rhinitis among Korean immigrants to the United States
      is unknown. However, after arrival in the United States, many develop allergic
      rhinitis for the first time. This study is undertaken to investigate and
      establish some contributing environmental factors and the time until onset of
      allergic rhinitis in Korean immigrants to the United States living in Chicago.
      Information regarding 246 patients of Korean origin who presented to a Chicago
      allergy/immunology clinic from 1993 to 1998 were analyzed by retrospective chart
      review. The diagnosis of allergic rhinitis was established by history, physical
      examination, and skin testing for immediate hypersensitivity to airborne
      allergens. The mean residential time in the United States of our patients was
      13.5 years (range, 2-38 years). The mean interval from arrival in the United
      States to onset of symptoms was 8 years (range, 0-24 years) The most commonly
      identified allergens were ragweed pollen (59%), cat pelt (44%), cocklebur pollen
      (41%), house-dust mite (35%), and Penicillium (29%). We conclude that the
      spectrum of responsible allergens in Korean immigrants closely resembles that
      seen in native citizens of the United States and that environmental factors play
      an important role in the pathogenesis of allergic rhinitis in this population.

PMID- 16598995
TI  - A novel air filtration delivery system improves seasonal allergic rhinitis.
AB  - Twenty percent of the United States population has respiratory allergies. The
      preferable treatment for allergies is avoidance. Bedrooms offer the best
      opportunity for allergen avoidance. Most previous studies of air filtration only
      measured the effect on allergen particle counts, but few have addressed the
      clinical efficacy. This study measured the effects of a novel laminar flow air
      filtration device (PureNight) on seasonal ragweed allergies. Seventy-seven
      percent of the subjects improved significantly on symptom scores, an average of
      26% improvement in the morning and 24% in the evening. Daytime sleepiness and
      quality of life scores also improved significantly in all subjects. Tolerability
      was excellent. The PureNight device provided significant clinical improvement of
      allergic symptoms during ragweed hay fever season.

PMID- 16598996
TI  - Sensitization to other foods in subjects with reported allergy to grapes.
AB  - The grape is widely produced and consumed in the Mediterranean area. The object
      of this prospective study was to present in detail the clinical features of
      patients with documented immunoglobulin E (IgE)-mediated reactions to grapes or
      its products as well as the existing cosensitizations in other food allergens
      among this population. Sixty-one patients (27 male patients and 34 female
      patients), aged 14-52 years (mean, 28.8 years) with a documented history of IgE
      mediated reactions to grapes or its products (wine, juice, and wine vinegar) were
      included in this study. In each patient, full allergological data, clinical
      examination, and specific in vivo (skin-prick tests and prick-to-prick) and in
      vitro (grape-specific IgE) evaluations were recorded. The diagnostic procedure
      was extended in other food allergens and molds for exclusion of fruit surface
      contamination. Thirty-seven of 61 (60.7%) patients had a positive personal
      history and 24/61 (39.3%) patients had a family history of atopy. Patients
      reported 3.1 episodes/patient (range, 1-15 episodes) after consumption of grapes
      or its product. Forty-seven of 61 (77%) patients had presented oral allergy
      syndrome after eating grapes before the first reported reaction. The mean time
      for the onset of symptoms was 42 minutes (4-160 minutes). Forty-four of 61
      (72.1%) patients reported more than one reaction. The observed prevalence of
      symptomatology according to the system involved was determined: skin,
      57/61(93.4%) patients; respiratory, 46/61(75.4%) patients; cardiovascular, 27/61
      (44.3%) patients; and gastrointestinal, 24/61(39.3%) patients. The main
      cosensitizations were identified (skin-prick tests): apples, 81.9%; peaches,
      70.5%; cherries, 47.5%; strawberries, 32.8%; peanuts, 49.2%; walnuts, 42.6%;
      hazelnuts, 31.1%; almonds, 26.2%; and pistachios, 29.5%. The grape and its
      products may be the offending agent of IgE-mediated reactions in sensitized
      individuals. The high prevalence of concomitant reactivity to other fruits
      elicits the interest of clinical relevance of these findings among the grape
      allergic population.

PMID- 16598997
TI  - Allergic fungal sinusitis presenting with proptosis and diplopia: a review of
      ophthalmologic complications and treatment.
AB  - Allergic fungal sinusitis is a noninvasive, but vigorous, inflammatory response
      to mold that occurs in immunocompetent patients with chronic sinusitis and nasal
      polyposis. It typically occurs in patients who have a history of atopic disease.
      Occasionally, the patients with allergic fungal sinusitis present with ophthalmic
      signs and symptoms--most commonly proptosis and diplopia. We report the case of a
      23-year-old man with right-sided proptosis, diplopia, and nasal obstruction. He
      had a history of sinusitis in the past. On presentation, sinus computed
      tomography scan showed pansinusitis. Subsequent workup revealed elevated
      immunoglobulin E and positive skin testing to several molds including Bipolaris
      spicifera and Aspergillus fumigatus. Functional endoscopic sinus surgery was
      performed, and the surgical specimen revealed allergic mucin with eosinophils,
      Charcot-Leyden crystals, and a silver stain showing fungal elements. His
      symptoms, including proptosis and diplopia, improved after surgical debulking and
      use of systemic corticosteroids.

PMID- 16598998
TI  - A 34-year-old man with chronic itching and peripheral and submucosal
      eosinophilia.
AB  - A 34-year-old man with peripheral eosinophilia, chronic pruritus, and colonic
      eosinophilic infiltration is presented as a patient-oriented problem-solving case
      report to show the important aspects of differential and specific diagnosis,
      treatment, prognosis, and caveats in the approach to the workup of the patient
      with eosinophilia. Allergic rhinitis, asthma, atopy, and drug-induced
      eosinophilia should come to mind in the initial differential diagnosis of any
      patient with peripheral eosinophilia. Also included in the differential after
      allergic disease processes would be the general categories of infectious,
      neoplastic, and the various forms of organ-specific eosinophilic infiltration and
      idiopathic syndromes. The importance of ruling out infectious causes for
      eosinophilia is paramount, especially given the dangers of immunosuppressive
      treatments often used to treat other conditions associated with eosinophilia.

PMID- 16598999
TI  - Allergic bronchopulmonary aspergillosis.
AB  - A case of allergic bronchopulmonary aspergillosis (ABPA) is presented, followed
      by a discussion of the clinical characteristics, pathogenesis, diagnosis, and
      management of this disease. Special emphasis is given to clinical pearls and
      pitfalls for the practicing allergist. ABPA is a hypersensitivity response to
      Aspergillus antigens in the lung and is distinct from other forms of Aspergillus
      pulmonary disease. Episodic bronchospasm, expectoration of mucous plugs, and
      fleeting pulmonary infiltrates are common manifestations of the disease. Several
      diagnostic schemes for ABPA have been described with varying criteria, which
      uniformly includes asthma and positive immediate skin-prick test to Aspergillus
      fumigatus. The mainstay of treatment for ABPA is corticosteroids, which are
      normally effective.

PMID- 16599000
TI  - Belief, reality, and self-deception in environmental and occupational health.

PMID- 16599001
TI  - The effect of alcohol, tobacco, and aspirin consumption on seminal quality among
      healthy young men.
AB  - In this study, the authors examined the effects of alcohol, tobacco, and drug use
      on plasma testosterone and seminal parameters (in accordance with the World
      Health Organization's standards) in healthy Argentine medical students (n = 34).
      Some alterations in seminal parameters were detected in 19 (56%) subjects.
      Alcohol and tobacco use were correlated significantly, p = 0.005; subjects who
      used these substances exhibited a nonsignificant reduction in sperm
      concentration, motility, viability, and normal morphology. There was a
      significant decrease in sperm motility among students who used moderate amounts
      of aspirin (i.e., > or = 500 mg/wk). The authors concluded that alcohol, tobacco,
      and aspirin use could have had detrimental effects on seminal parameters and that
      men who wish to procreate should be warned of such effects. Doses, exposure time,
      and interactions with other variables deserve additional study.

PMID- 16599002
TI  - Assessment of sources of second-hand smoke exposure in a putatively unexposed
      population.
AB  - The authors sought to determine levels of urinary cotinine and its association
      with collateral exposure to second-hand smoke in public health workers. Urinary
      cotinine was measured twice at 1-wk intervals in 28 public health workers or
      their spouses. Information on sources of second-hand smoke exposure and a dietary
      history were obtained from each participant. Geometric mean and median cotinine
      levels were 2.74 and 2.33 ng/mL, respectively. Only 6 instances of second-hand
      smoke exposure were reported from a combined 204 days of potential exposure, and
      these did not correspond to higher cotinine values. There was no association
      between consumption of foods containing nicotine and log-transformed urine
      cotinine levels (p = .80). The authors' analysis indicates dietary sources of
      nicotine are not important, even for persons with very low urinary cotinine
      levels. Further study is needed to determine sources of variation in urinary
      cotinine among largely unexposed populations.

PMID- 16599004
TI  - Neuropsychological effects of long-term low-level organophosphate exposure in
      orchard sprayers in England.
AB  - The health effects from prolonged low-level organophosphate exposure are unknown.
      We hypothesized that exposed individuals would show neuropsychological decrements
      when compared with unexposed individuals, and that cumulative organophosphate
      exposure would be correlated with neuropsychological performance. We used a
      quasiexperimental cross-sectional design to compare neuropsychological test
      scores among three groups: orchard sprayers exposed to organophosphates, and
      construction worker and pig farm workers who were not exposed. Relative to
      construction workers, orchard sprayers were significantly slower on negative
      statements of the syntactic reasoning test. However, we found no relationship
      between cumulative exposure and test response. The slower response of the orchard
      sprayers was apparently exposure-related, but we could not identify an underlying
      neurotoxic mechanism. Therefore, we are unable to conclude whether this is a
      specific cognitive effect, or a decrement arising on the most sensitive test
      employed.

PMID- 16599005
TI  - Guillain-Barre syndrome in a rural farming district in South Africa: a possible
      relationship to environmental organophosphate exposure.
AB  - Although organophosphate (OP) insecticides have been recognized as having
      neuropathic potential, a relationship with Guillain-Barre syndrome (GBS) has not
      been previously confirmed. A cluster of 7 cases of GBS was noted over an 11-yr
      period in an isolated farming region in the Northern Cape Province of South
      Africa, an area subject to intensive aerial application of OP insecticides.
      Observed cases were more than 4 times higher than expected based on a Poisson
      probability distribution. Four cases were clustered in an area where the
      topography showed a marked hollow, and where spray drift of aerial OP
      insecticides was anticipated. The rate of GBS in this subcluster was more than 14
      times higher than expected. The authors explored the hypothesis that aerial OP
      insecticide application was related to the raised incidence of GBS in this area
      and made suggestions for future research.

PMID- 16599003
TI  - Serum DDT and DDE levels in pregnant women of Chiapas, Mexico.
AB  - The authors measured the main ingredients of technical DDT (1,1,1-trichloro-2,2
      bis(p-chlorophenyl [p,p'-DDT]) and its principal metabolite, 1,1-dichloro-2,2-bis
      (p-chlorophenyl)ethylene [p,p'-DDE]) in serum collected from 52 pregnant women in
      Tapachula, Chiapas, Mexico in 1998. The median lipid-adjusted serum levels for
      the women were 676 ng/g p,p'-DDT (range: 56-23,169 ng/g) and 4,843 ng/g p,p'-DDE
      (range: 113-41,964 ng/g). In regression analysis, serum DDT and DDE increased
      with age (test for trend, p = .022) but decreased with total lactation (test for
      trend, p < .001). Residence in a house that had ever been sprayed for malaria
      control was also related to serum DDT and DDE. This study provides evidence of
      high-level exposure to DDT and DDE among pregnant women living in Chiapas,
      Mexico, despite countrywide restrictions on its use at the time.

PMID- 16599006
TI  - Thyroid function of newborns and exposure to chlorine dioxide by-products.
AB  - In this study, the authors compared thyroid function of newborns from 11
      municipalities where drinking water was disinfected by chlorine dioxide (ClO2)
      with that of newborns from 15 municipalities using chlorine disinfection. They
      estimated the mean neonatal blood thyroid stimulating hormone (TSH) levels and
      proportion of congenital hypothyroidism cases using the results of the Quebec
      neonatal screening for congenital hypothyroidism for 32,978 newborns over the
      period 1993-1999. There was no significant increase in the TSH level and no
      excess of congenital hypothyroidism when all newborns exposed to ClO2 were
      considered. However, for newborns with low birth weight, mean TSH level was
      significantly higher among those exposed to ClO2 than for those in the reference
      group.

PMID- 16599007
TI  - Polymorphisms in glutathione-related genes affect methylmercury retention.
AB  - Methylmercury is eliminated from the human body as glutathione (GSH) conjugates.
      GSH production is mediated by glutamyl-cysteine ligase (GCL) and conjugation by
      glutathione S-transferases (GST). In this study, the authors tested whether
      polymorphisms in GCL and GST genes modify methylmercury retention. Erythrocyte
      mercury concentration (EryHg), plasma polyunsaturated fatty acids (PPUFA), and
      genotype for GCLC, GCLM, GSTA1, GSTM1, GSTP1, and GSTT1 were determined in 365
      individuals. A general linear model was developed for analyzing whether genotype
      modified the regression of EryHg on PPUFA. The presence of one variant allele for
      either GCLC-129 or GSTP1-114 was associated with higher EryHg and steeper
      regression slope. No similar trends were shown for GCLM, GSTA1, GSTM1, or GSTT1.
      These findings indicate that GCLC polymorphisms that affect GSH production also
      affect methylmercury retention, and that GSTP1 may play a role in conjugating
      methylmercury with GSH.

PMID- 16599008
TI  - Domestic exposure to legionellae for Dutch Legionnaires' disease patients.
AB  - The source of infection for travelers who develop Legionnaires' disease (LD)
      shortly after a journey abroad is difficult to ascertain. Infection is likely to
      have occurred abroad, but could also have occurred at the patient's own
      residence. The authors conducted a case-control study to determine risk for
      acquiring LD at home in the Netherlands after traveling abroad. They compared
      homes of 44 traveling LD patients with 44 homes of nontraveling LD patients,
      using logistic regression models. Geographic distribution was confounding the
      association between traveling and presence of Legionella spp. in residences;
      adjustment was necessary. In traveler's homes, legionellae were present more
      often, with crude and adjusted OR (95% CI) being 1.6 (0.5-5.0) and 1.4 (0.4-4.4),
      respectively. The authors' findings indicate that the patient's residence can be
      a potential source of infection after traveling.

PMID- 16599009
TI  - Perinatal mortality in West Germany following atmospheric nuclear weapons tests.
AB  - Using trend analysis, the author sought a possible association between perinatal
      mortality rates in West Germany, 1955-1993, and the fallout from atmospheric
      nuclear weapons testing in the years 1952-1993. The regression model used a
      continuously falling trend and a superimposed extra term that reflects the
      average strontium content in pregnant women. Mortality rates show an upward
      deviation that peaked in 1970. The model attributes more than 100,000 excess
      perinatal deaths to strontium in the fallout. The dose-response curve is
      curvilinear with a power of dose of 1.81 +/- 0.23. In addition, using a combined
      regression model, the author analyzed the two data subsets of perinatal mortality
      (i.e., stillbirth rate and early neonatal mortality). The strontium effect is 3.4
      times greater on early infant deaths than on stillbirths. According to the
      prevailing wisdom, the fetus is protected against damage from ionizing radiation
      by a threshold dose of 50-200 mSv, but the doses from strontium in the fallout
      were well below 1 mSv/yr in Germany. The results reported here seem to contradict
      the existence of a threshold dose for perinatal mortality at low doses.

PMID- 16599010
TI  - Young infants' morbidity and exposure to fine particles in a region with two
      power plants.
AB  - This study investigated the effect of fine particulate matter (PM2.5) in ambient
      air on hospital admissions and emergency room (ER) visits among young children (0
      3 yr) residing in 4 communities in southern Israel, within an area 5-25 km from
      the 2 power plants, which operate within 25 km of each other. Daily records of
      hospitalizations and ER visits for respiratory diseases at the 3 hospitals
      serving the region were examined for 9 mo, October 1, 2000-June 30, 2001. Mean
      PM2.5 concentrations for the four communities ranged from 11.6 to 28.1 microg/m3.
      Time series analysis revealed a statistically significant association (p < 0.05)
      between the numbers of hospitalizations and ER visits for respiratory symptoms
      and concentrations of PM2.5. This effect was evaluated for 0-3 lag days,
      directly, and for interactions with temperatures and seasonal parameters. The
      respiratory health of young children may be affected by 24 hr concentrations of
      PM2.5 < 60 microg/m3, the threshold proposed by both Israel and the United
      States.

PMID- 16599011
TI  - Prevalence of byssinosis in a textile mill in northern Greece.

PMID- 16599012
TI  - Uric acid: an additional component of metabolic syndrome?

PMID- 16599013
TI  - Laparoscopic uterosacral nerve ablation and chronic pelvic pain.
AB  - Chronic pelvic pain is a complicated syndrome comprised of different types of
      pain, including dysmenorrhea, deep dyspareunia, and intermenstrual pain, which
      can make interpretation difficult. Therefore, investigation of this complex
      syndrome requires very careful consideration. Accumulating data from several
      randomized studies, we have now come to realize that LUNA can be an option in a
      few circumstances, especially for control of menstrual pain without
      endometriosis; however, its effectiveness may not extend to other indications,
      such as alleviating secondary dysmenorrhea associated with endometriosis
      (although it could, however, be reached by presacral neurectomy). Juang et al's
      article reports a very preliminary experience in the treatment of primary deep
      dyspareunia, presenting a promising perspective yet without sufficient evidence
      on the management of deep dyspareunia. A randomized controlled study with an
      adequate number of patients is warranted.

PMID- 16599014
TI  - Is hyperuricemia another facet of the metabolic syndrome?
AB  - BACKGROUND: Hyperuricemia is commonly associated with obesity, glucose
      intolerance, hypertension, dyslipidemia, and atherosclerotic cardiovascular
      disease. The resemblance of the metabolic syndrome and hyperuricemia has led to
      the suggestion that hyperuricemia is a part of the metabolic syndrome. The
      purpose of this study is to examine the contribution of uric acid (UA) as an
      additional component of the metabolic syndrome in middle-aged men. METHODS: In
      total, 393 male participants, aged 45-60 years, were recruited from a
      professional health evaluation program. Anthropometric measurements and blood
      pressure (BP) were taken after an overnight fast. Fasting blood samples were
      collected for the measurements of glucose, UA, and lipid profile. Logistic
      regression models were fitted to examine the relationship between UA and the
      diagnosis of metabolic syndrome. Factor analysis was performed to explore the
      relationship between UA and the components of the metabolic syndrome. RESULTS:
      The diagnosis of the metabolic syndrome was significantly associated with waist
      circumference (WC), glucose, triglycerides (TG), high-density lipoprotein
      cholesterol (HDL-C), systolic BP, and liver enzyme levels, but not associated
      with UA levels. The sensitivity of hyperuricemia (serum UA > or = 7.0 mg/dL) for
      the diagnosis of the metabolic syndrome was 58.0% and the specificity was 55.3%.
      In factor analysis, UA aggregated with body mass index, WC, glucose, log TG, and
      HDL-C as a metabolic factor. Systolic and diastolic BP were loaded on a second
      factor separately. The model loaded with UA explained a similar proportion of the
      total variance (56.9%), as did the model loaded without UA (62.5%). CONCLUSION:
      Our results suggest that the contribution of UA as an additional component of the
      syndrome seems to be insignificant. We propose that hyperuricemia might not be an
      important facet for the understanding of the underlying structure of the
      metabolic syndrome.

PMID- 16599015
TI  - Treatment of primary deep dyspareunia with laparoscopic uterosacral nerve
      ablation procedure: a pilot study.
AB  - BACKGROUND: This pilot study was undertaken to evaluate the effect of
      laparoscopic uterosacral nerve ablation (LUNA) for treatment of primary deep
      dyspareunia. METHODS: Between July 2002 and June 2003, 12 consecutive patients
      diagnosed with primary deep dyspareunia were treated with the LUNA procedure. The
      evaluation scoring system included the Hospital Anxiety and Depression Scale and
      the revised Sabbatsberg Sexual Rating Scale, done at baseline and 3, 6, and 12
      months after LUNA. RESULTS: At the initial 3-month follow-up period, 3 patients
      were very satisfied with their treatment, 5 were satisfied, 2 uncertain, 1
      dissatisfied, and 1 very dissatisfied. The corresponding figures at the 12-month
      follow-up visit were 2, 4, 4, 1, and 1, respectively. Overall, 8 (66.7%) patients
      in this trial were very satisfied or satisfied at the initial postoperative
      evaluation and 6 of them (50.0%) remained satisfied at the final evaluation.
      CONCLUSION: Over half of the study patients felt satisfied with the results of
      treatment with LUNA. Further prospective controlled clinical trials are mandatory
      to validate its effectiveness.

PMID- 16599016
TI  - Hyponatremia among the institutionalized elderly in 2 long-term care facilities
      in Taipei.
AB  - BACKGROUND: Hyponatremia is common in the institutionalized elderly, and syndrome
      of inappropriate antidiuretic hormone secretion was deemed the most important
      etiologic factor. The purpose of this study was to evaluate the prevalence and
      etiologic factors of hyponatremia among institutionalized elderly and to explore
      its association with nutritional status. METHODS: Subjects in 2 private long-term
      care facilities (LTCFs) participated in this study. Periodic nutritional
      evaluations, including anthropometric measurements and serial laboratory
      examinations, were performed every 6 months. When hyponatremia was identified,
      serum osmolality, serum levels of cortisol, thyrotropin, antidiuretic hormone,
      urine osmolality, and electrolyte profile were done instantly. Water loading
      tests were performed for subjects with euvolemic, hypo-osmolar hyponatremia.
      Nutritional status (i.e. hemoglobin, serum albumin, serum total cholesterol, body
      mass index [BMI], and mean body weight loss within 6 months) was compared between
      hyponatremic and normonatremic subjects during hyponatremic episodes and at
      follow-up (6 months later). RESULTS: In total, 67 (mean age = 77.2 +/- 8.8 years,
      M/F = 45/22) LTCF residents were enrolled. The prevalence of hyponatremia was
      31.3% (21/67) during the 6-month period, and 62.5% of these cases were related to
      reset osmostat. In addition, BMI was similar between hyponatremic and
      normonatremic subjects during hyponatremic episodes (19.1 +/- 3.2 vs 20.5 +/- 4.0
      kg/m2, p = 0.16), but became significantly lower in hyponatremic subjects 6
      months later (18.5 +/- 3.2 vs 20.8 +/- 4.2 kg/m2, p = 0.027). However, the mean
      body weight loss during the 6-month follow-up was similar (3.0% vs 0.8%, p =
      0.25). Furthermore, hemoglobin and serum levels of albumin were similar between
      groups during hyponatremic episodes and at follow-ups, but serum levels of total
      cholesterol were significantly lower in hyponatremic subjects on both occasions
      (166.9 +/- 30.5 vs 190.2 +/- 38.2 mg/dL, p = 0.016 during hyponatremic episodes
      and 153.6 +/- 29.4 vs 182.8 +/- 35.5 mg/dL, p = 0.003 at follow-up). CONCLUSION:
      About a third of LTC-dwelling elderly would experience hyponatremia during the 6
      month period, and 62.5% of them were due to reset osmostat. The relationship
      between hyponatremia and undernutrition deserves further investigation.

PMID- 16599017
TI  - Sarcoma of the larynx: treatment results and literature review.
AB  - BACKGROUND: Sarcomas of the larynx are rare neoplasms that constitute less than
      1% of laryngeal malignancies. A Medline search found no large series focusing on
      laryngeal sarcomas. We reviewed the cases of laryngeal sarcomas treated in our
      cancer center and compared our experiences and treatment results with those from
      other centers. METHODS: A retrospective review of 10 patients with laryngeal
      sarcoma treated in our institute between 1980 and 2000 was done to identify tumor
      characteristics, therapeutic modalities, and treatment outcomes. RESULTS: The
      patients showed a male predominance (9/10) and presented 8 types of pathology.
      Nine patients underwent surgery, including 2 total laryngectomy, 4 partial
      laryngectomy, and 3 endoscopic laser cordectomy. During a median follow-up of 92
      months, the 5-year overall survival and disease-specific survival were 76% and
      90%, respectively. Two patients developed recurrence, including 1 local
      recurrence and 1 distant metastasis. CONCLUSION: Surgical intervention was the
      first choice in the treatment of laryngeal sarcomas. The prognosis is relatively
      good when compared with sarcoma originating from other anatomic sites.

PMID- 16599018
TI  - Primary aldosteronism caused by unilateral adrenal hyperplasia: rethinking the
      accuracy of imaging studies.
AB  - A rare type of aldosteronism, known as unilateral adrenal hyperplasia (UAH), is
      difficult to diagnose, not only because it fails to conform to the typical common
      subtypes, but also because imaging results are unreliable. We report 2 Taiwanese
      patients with UAH. Case 1 was a 44-year-old man with 2 episodes of hypokalemic
      paralysis. Hypertension and suppressed plasma renin activity (PRA) with elevated
      plasma aldosterone concentration (PAC) were observed. Abdominal computed
      tomography (CT) and magnetic resonance imaging (MRI) showed a right adrenal mass,
      but adrenal scintigraphy revealed no definite laterality. The patient underwent a
      laparoscopic right adrenalectomy. Adrenal cortical hyperplasia was discovered
      from results of the histologic analysis. Case 2 was a 33-year-old woman referred
      for hypokalemia, hypertension, and a left adrenal mass found on a CT scan.
      However, MRI revealed normal adrenal glands. The adrenal vein sampling for PAC
      showed overproduction of PAC from the left adrenal gland. A laparoscopic left
      adrenalectomy was done. Pathology results revealed micronodular cortical
      hyperplasia with central hemorrhage. Blood pressure, plasma potassium,
      aldosterone, and renin activity levels returned to normal after operation in both
      cases. Both patients have been well for 3 years and 16 months, respectively,
      after surgery. We review the literature and discuss the limitations of imaging
      studies.

PMID- 16599019
TI  - Onset of systemic lupus erythematosus during pregnancy.
AB  - When systemic lupus erythematosus (SLE) is first suspected during pregnancy,
      though rare, the diagnostic criteria are not different from those for nonpregnant
      women. The pregnancy outcome is good if treatment with adequate immunosuppressive
      agents starts as soon as the diagnosis is made. There are 4 cases in this report
      who had SLE onset during pregnancy. Although 2 of them suffered from
      preeclampsia, all 4 pregnancies resulted in favorable outcomes after the lupus
      was controlled by medical treatment.

PMID- 16599020
TI  - Coexistence of peripheral primitive neuroectodermal tumor and tetralogy of
      Fallot.
AB  - We describe a little girl with tetralogy of Fallot (TOF) who was found to have a
      huge peripheral primitive neuroectodermal tumor (pPNET) when she developed
      progressive difficulty in standing and crawling at the age of 11 months. The
      tumor was located in the left paraspinal region (T4-T12), with intraspinal
      extension causing severe compression. Nine days after surgical decompression with
      laminectomy, chemotherapy was initiated with alternative courses of vincristine,
      doxorubicin, cyclophosphamide, etoposide, and ifosfamide every 3 weeks. The
      muscle power in her legs recovered substantially after 2 courses of chemotherapy.
      Although peripheral blood for cytogenetic study revealed no chromosome
      abnormality, recent cytogenetic analysis has revealed a high frequency of
      reciprocal translocation t(11;22)(q24;q12) detected in pPNET and a strong
      association between TOF and chromosome 22q11 microdeletion (del 22q11). Both
      genetic defects involve chromosome 22q in the close region. This case report
      illustrates the necessity of investigating for cytogenetic change in chromosome
      22 and close follow-up due to the possibility of subsequent development of
      malignancies in patients with TOF.

PMID- 16599021
TI  - Simple device for treating prolapsing loop colostomy.
AB  - Stoma prolapse is a common complication of intestinal stoma. Although various
      surgical methods yield satisfactory results, nonsurgical treatment may be better
      for a temporary stoma. We report a case of a patient with a distal limb prolapse
      of a right transverse colostomy who received nonsurgical treatment with
      satisfactory results. For the treatment of a temporary transverse loop colostomy
      with distal limb prolapse, we designed a simple device consisting of a pediatric
      plastic medicine cup, which was rolled into a towel to shape the bottom of the
      cup into a compressor. The towel was put on the stoma outside of the colostomy
      bag with the compressor above the prolapsing limb of the colostomy. An abdominal
      binder was applied to fix the towel.

PMID- 16599022
TI  - Mixed epithelial and stromal tumor of the kidney.
AB  - A 42-year-old female presented with intermittent left flank pain for 2 years. She
      developed gross hematuria 1 month prior to seeking help. Intravenous pyelography
      showed filling defects within the lower portion of the left collecting system and
      renal pelvis causing hydronephrosis. Abdominal computed tomography revealed a
      huge cystic heterogenic tumor about 20 cm in largest diameter occupying the
      entire left kidney. A left radical nephrectomy was performed without
      complications. The pathology report confirmed the diagnosis of mixed epithelial
      and stromal tumor of the kidney. From pathologic survey, the spindle cells of
      this tumor were positive for muscle markers and expressed estrogen and/or
      progesterone receptors. We suggest that a mixed epithelial and stromal tumor of
      the kidney should be considered in all cystic renal tumors presenting in
      perimenopausal women.

PMID- 16599023
TI  - Disaster, mental health and rescuing medical professionals.

PMID- 16599024
TI  - Flow cytometric and demographic analysis of t cell acute lymphoblastic leukemia
      in Pakistani population.
AB  - BACKGROUND: This study was carried out to analyze the proportion of T cell acute
      lymphoblastic leukemia (TALL) among all acute lymphoblastic leukemia (ALL) in
      Pakistani population and its correlation with the demographic features. Accuracy
      of cell surface markers used in flow cytometric analysis of the leukemic cells
      was also determined. METHODS: Data of 209 consecutive cases of acute
      lymphoblastic leukemia (ALL) presenting between July 1995 and July 2003 was
      analyzed. Flow cytometry was performed on all ALL cases using the standard
      protocols. TALL markers included CD3, CD5 and CD7. RESULTS: Proportion of TALL
      among known ALL Pakistani patients was 17.22%. Mean age of the TALL patients was
      17.2 years. Proportion of TALL was higher in adults than in children (21.95% vs.
      14.17%). Overall in this study there were more male patients affected by TALL
      (25/36 or 69.40%) than females (11/36 or 30.60%). The female to male ratio among
      TALL patients was 1:2.27. However, the proportion (%) of TALL in females was
      higher than males (18.96% vs. 15.82 %) i, e, 1.2:1. CD7 was found to be the most
      sensitive among both adults & children. It was positive in 94.4% of the TALL
      cases. CONCLUSION: Proportion of TALL among ALL in Pakistan is similar to that
      reported in this region, indicating a candidate association with geographical
      location and socioeconomic status. The reactivity of markers with TALL. cells was
      similar to what we expected based upon literature. However, due to some aberrant
      and cross reactivity displayed by each marker, we strongly recommend a panel
      approach including B and myeloid markers to ensure a correct diagnosis of TALL.

PMID- 16599025
TI  - Frequency of irritable bowel syndrome in college students.
AB  - BACKGROUND: This study was carried out to investigate the presence of irritable
      bowel syndrome (IBS) in college students and compare its distribution in the non
      medical college and medical college students. METHODS: We collected data from 508
      students by inviting them to fill out a questionnaire based on Rome II criteria
      for the diagnosis of IBS from November 2001 to February 2004. Two major cities
      Karachi and Bahawalpur were selected and it was coordinated by the section of
      Gastroenterology, Department of Medicine, Aga Khan University Hospital and Quaide
      Azam Medical College, Bahawalpur. RESULTS: A total of 508 subjects with males 43%
      (220/508) and female 57 % (288/508) mean age 22 +/- 2.8 years responded to the
      questionnaire. The overall frequency of IBS among college students was 34%
      (171/508). There were 41% (107/263) non-medical college and 26 % (64/245) medical
      college students with IBS. Abdominal pain was present in 100% (171/171) with
      altered frequency of stool in 58% (100/171) (p< 0.001, OR 12.5, CI 7.9-20.0) of
      students with IBS. The medical advice was sought by 38% (65/171) in IBS group
      with 46% (30/65) non-medical college school and 54 % (35/65) medical student
      (p=0.001, OR 1.9, CI 1.3-2.8). CONCLUSION: IBS is common in younger adult
      population of Pakistan. Its prevalence is higher in non-medical college students
      but health care seeking behavior was more common in medical students.

PMID- 16599026
TI  - Efficacy and adverse effects of oral iron chelator deferiprone (l1, 1,2- dimethyl
      3-hydroxypyrid-4-one) in patients with beta thalassaemia major in Pakistan.
AB  - BACKGROUND: Deferiprone (DFP,L1) is a bidentate oral iron chelator which binds to
      iron in a 3:1 ratio. It has the potential advantage of reduced cost and increased
      compliance. We conducted a study in order to determine the efficacy and adverse
      effects of DFP in Pakistani thalassaemic patients. METHODS: A group of 26
      thalassaemic patients entered the study during the period Jan 1999 to Aug 2002.
      DFP supplied by Lipomed, Switzerland was given at a daily dose of 75 mg/kg/day
      (range 50-75 mg/kg/day). After giving informed written consent all the patients
      were subjected to clinical examination and investigations for monitoring the
      response. Blood complete picture, liver function tests, blood urea & creatinine,
      antinuclear factor antibodies (ANF) were tested in all cases before starting DFP
      treatment. RESULTS: The patients ages ranged from 11 to 27 years, 16 were male
      and 10 were female. Initial serum ferritin level ranged from 3100-8800 microg/l,
      mean serum ferritin level was 7129 +/- 1467 microg/l (95% CI 6536 - 7721
      microg/l). ECG and Echocardiography was performed in all cases and in 11 cases
      Cardiac Multigated acquisition (MUGA) Scan was also performed and six patients
      with impaired left ventricular function were identified. Four patients were lost
      to follow up and one patient died due to cardiomyopathy. Among the remaining 21
      patients serum ferritin levels dropped to 1900 microg/l to 5600 microg/l with
      mean level of 4288 microg/l (95%CI 3874 - 4702 microg/l), SD 911 microg/l.
      Significance of difference was (p < 0.001) by Paired samples 't' test. Six
      patients had gastrointestinal symptoms along with two having arthropathy. ANF
      positivity was not detected in any patient while on DFP treatment. Similarly,
      agranulocytosis was not detected in any patient. CONCLUSION: Mean serum ferritin
      level estimated at the start of trial was 7129 microg/l. This shows that
      Pakistani thalassaemic patients are quite iron overloaded due to socioeconomic
      reasons that are peculiar to our setup. In this study DFP was well tolerated and
      caused fewer side effects. It had much better patient compliance and was
      effective in lowering serum ferritin level in previously most poorly chelated
      patients.

PMID- 16599027
TI  - Bacillus Calmette-Guerin (BCG) lymphadenitis-changing trends and management.
AB  - BACKGROUND: Bacillus Calmette-Guerin (BCG) vaccination is performed as a part of
      expanded Programme of Immunization (EPI). Suppurative lymphadenitis is the common
      complication of BCG vaccination. The optimum treatment for this complication is
      debated. METHODS: All cases of BCG lymphadenitis presenting to pediatric surgical
      service over a 17-year study period were reviewed to determine the optimum
      treatment for this problem. RESULTS: Sixty children were referred for the
      management of BCG lymphadenitis during the study period. Most patients (n=43)
      presented during 1988 and 1990. Children were healthy and received BCG (Pasteur
      strain) vaccination at EPI during first 2 months of life. Initially all the
      patients received medical treatment with anti-tuberculous drugs for one to nine
      months. Fifty-two children who presented with large (approximately 3cm) fluctuant
      lymph nodes, required a surgical procedure to avoid spontaneous rapture and sinus
      formation (Group A), whereas medical treatment was effective in five out of eight
      patients presenting with small (approximately 1 cm) nodes (Group B). CONCLUSIONS:
      Medical treatment with antituberculous drugs is not effective to treat BCG
      lymphadenitis, when the involved lymph nodes are around 3.0 cm and have developed
      fluctuation and inflammation of over lying skin.

PMID- 16599028
TI  - Dermatophyte growth and degradation of human stratum corneum in vitro
      (pathogenesis of dermatophytosis).
AB  - BACKGROUND: This study was carried out to determine growth of dermatophytes using
      human stratum corneum in vitro and the degrading effect of Keratinases
      (Proteinases) on stratum corneum for a complete understanding of the host
      parasite relationship. METHOD: Trichophyton rubrum isolates derived from patients
      with tinea cruris infections were obtained from the Department of Medical
      Microbiology, University Hospital of Wales, U.K. Human stratum corneum sterilized
      with ethylene oxide was used as a nitrogen source in agar culture medium plates.
      RESULT: Fungal growth took place in plates which contained human stratum corneum
      particles while there was no growth in the plates without stratum corneum at
      three weeks after initiation. There was a gradual disappearance of the particles
      of stratum corneum from the plates at the end of the third week CONCLUSION: The
      growth of organisms in plates with human stratum corneum and their disappearance
      at third week suggested that stratum corneum was not only source of nutrition for
      the dermatophytes, but also the growing fungal mycelia and the proteinases
      induced by them were playing a part in the digestion of granules and thus may
      have an important role in the pathogenesis of dermatophyte infections.

PMID- 16599029
TI  - Outcome of endoscopic therapeutic interventions: are they different among various
      non-malignant esophageal diseases.
AB  - BACKGROUND: This study was carried out to evaluate and compare the outcome of
      various causes of non-malignant lesions of the esophagus after endoscopic
      therapeutic intervention. METHODS: A cohort of patients with non-malignant
      dysphagia presenting at Aga Khan University hospital, a tertiary care setting who
      underwent endoscopic intervention was studied. Response to treatment was
      evaluated by improvement in dysphagia score on a scale of 0-4 and weight gain.
      RESULTS: 99 subjects (53 males) were included. Mean age was 48.6 +/- 17.2 years.
      Dysphagia for solids was present in 48%, for liquids in 3% and for both in 49%
      patients. Significant weight loss (>10% body weight) occurred in 35 (35.3%)
      patients. Achalasia was diagnosed in 49.5%, peptic stricture in 30.4%, post
      sclerotherapy stricture in 12.1%, corrosive injury in 4%, post-operative
      stricture in 4%. In comparative analysis of achalasia and inflammatory groups,
      good response to dysphagia was seen in 40/49 (82%) and 22/50 (44%) respectively p
      < 0.001. Weight gain was 35/49 (72%) and 22/50 (44%) p <0.001 respectively.
      Significantly, more endoscopic sessions were required in inflammatory group
      compare to achalasia; 2.2 and 1.1 respectively; p <0.001 and 160% complications
      rate in inflammatory group comparing to no complications in achalasia.
      CONCLUSIONS: Dysphagia and weight loss were common presentations in non-malignant
      esophageal diseases. Therapeutic intervention in inflammatory group was
      associated with high complication than the achalasia group.

PMID- 16599030
TI  - Assessing the effects of training on knowledge and skills of health personnel: a
      case study from the family health project in Sindh, Pakistan.
AB  - BACKGROUND: The Family Health Project (FHP) was implemented in the province of
      Sindh during 1992-99 with the assistance of the World Bank. The project was
      designed to bring substantial changes in health care system for achieving
      improvement in the health status by strengthening the quality and integration of
      primary health care services. One of the major components of the project was to
      develop the institutional capacity of Ministry of Health in Sindh. This is a
      comparative analysis to assess the knowledge and skills of health care providers
      in Area Focus Approach (AFA) health facilities with the ones in non-AFA health
      care facilities. METHODS: In order to obtain a representative sample, 8 districts
      were selected which included, Larkana, Khairpur, Nawabshah, Dadu, Tharparkar,
      Thatta, Karachi South, and Karachi West. A structured questionnaire was designed
      with various sections to assess the knowledge and skills of various cadres of
      health facility staff. RESULTS: This comparative assessment has come up with some
      interesting results; there is a difference between the scores of knowledge and
      skills between AFA and non-AFA health care providers. This assessment identified
      some important methodological issues such as the use of base-line information for
      comparing the results and the selection of a comparable study population for
      controlling the confounding factors. CONCLUSIONS: These findings can be used as
      important lessons learned for producing better results of any post training
      assessment intervention.

PMID- 16599031
TI  - Effect of providing free sputum microscopy service to private practitioners on
      case notification to National Tuberculosis Control Program.
AB  - BACKGROUND: This study was undertaken to see whether providing free sputum
      microscopy services to private practitioners helps in case notification to the
      national tuberculosis control program. The knowledge, attitudes and practices of
      these practitioners regarding tuberculosis were also evaluated. METHODS: A
      questionnaire was administered to all the private practitioners practicing in a
      densely populated area of Karachi. They were asked to fill tuberculosis
      notification cards for the first three months and then for another three months
      when an incentive in the form of free sputum microscopy was provided to the
      practitioners. RESULTS: Although the majority of the practitioners knew that
      cough, fever and weight loss are the main symptoms of tuberculosis, less than
      half knew that blood in sputum, poor appetite and chest pain could also be
      associated with tuberculosis. Only 66% of the practitioners indicated sputum
      microscopy as the preferred diagnostic method for tuberculosis. Only 50% of the
      practitioners self treated the patients, while the remaining half referred their
      patients to specialists. Around 80% of the practitioners were aware of the four
      first-line anti-tuberculosis drugs. Less than half of the practitioners
      considered sputum microscopy as the most useful follow-up investigation in a
      patient with pulmonary tuberculosis. Generally, there was a poor response in case
      notification by private practitioners on provision of free sputum microscopy.
      CONCLUSION: An overwhelming majority of the practitioners had poor knowledge
      concerning the correct treatment practices in Tuberculosis. Providing sputum free
      microscopy does not significantly help in improving tuberculosis case
      notification. Strategies for public-private collaboration in tuberculosis control
      are needed.

PMID- 16599032
TI  - Aggressive revascularization in patients with critical lower limbs ischemia.
AB  - BACKGROUND: This study was conducted to conduct an audit of our policy of
      aggressive arterial reconstruction in patients with critical lower limb ischemia,
      so as to determine the success in treatment of these cases in terms of limb
      salvage and patient survival. METHODS: This study was carried out at department
      of general and vascular Surgery, Combined Military Hospital Rawalpindi from
      January 1995 to January 2000. A total of 114 cases were studied. All patients
      were admitted for assessment of an ischemic leg. Pre operative angiography was
      routinely performed. All patients underwent definitive treatment (bypass surgery,
      amputation and lumber sympathectomy) within three days of admission. Pre
      operative risk factors including age, sex, pre-existing diabetes mellitus,
      presenting symptoms, ankle systolic pressure were evaluated, with their effect on
      limb salvage and patient survival. RESULTS: Of the 114 cases included 102 (89.5%)
      were males. Forty-six patients (40.3%) were diabetic. Revascularization was
      attempted in 76 limbs, 61 (80.3%) underwent femoropopliteal bypass and 15 (19.7%)
      underwent femorodistal bypass. Twenty patients (17.5%) with Berger's disease, of
      the 114 cases included, were treated by lumbar sympathectomy. Eighteen limbs were
      beyond salvage necessitating amputation. Risk factors had no effect on limb
      salvage or mortality. Overall mortality was 4% and over all 30-day graft patency
      rate was 77.7%. One-year graft patency rate was 62.5%. CONCLUSION: By pursuing an
      aggressive policy of revascularization, good results can be obtained in terms of
      limb salvage and survival rates.

PMID- 16599033
TI  - Comparison of metoclopramide, prochlorperazine and placebo in prevention of
      postoperative nausea and vomiting (PONV) following tonsillectomy in young adults.
AB  - BACKGROUND: Postoperative nausea and vomiting following anaesthesia and surgery
      are common and can create considerable problems regarding management of patients
      and outcome of the surgical procedure. METHODS: This study evaluates and compares
      the efficacy and safety of the metochlopramide to that of prochlorperazine in the
      prevention of postoperative nausea and vomiting after tonsillectomy in young
      adult patients. 150 patients, of either sex, undergoing tonsillectomy under the
      same anaesthetic technique were studied in a randomized, double blind, placebo
      controlled manner. Either metoclopramide 0.1-0.2 mg kg(-1), prochlorperazine 0.1
      0.2 mg kg(-1) or 5% Dextose and normal saline (5% D/N.S) (2ml) as placebo was
      injected intravenously 10 minutes before induction of general anaesthesia.
      Episodes of nausea, retching/vomiting, adverse events, vital signs, the need for
      rescue antiemetic drug (metoclopramide 0.1-0.2 mg kg(-1) IV) were recorded until
      four hours from the end of the surgical procedure. RESULTS: The overall frequency
      of PONV was 18%, 16%, and 24% in group A (metoclopramide), B (prochlorperazine)
      and C (placebo) respectively. The need for rescue antiemetic was 2%, 8% and 12%
      in Prochloperazine group, metoclopramide group and control group respectively.
      These differences did not reach statistical significance (P>0.05). During the
      study period 82%, 84% and 76% of patients in group A, B and C respectively were
      found free from postoperative nausea and vomiting, and no adverse events related
      to either of the test medication were noted in any patient. CONCLUSION: It is
      concluded that the differences in the results of occurrence of PONV in the
      experimental group and control group are not statistically significant. However
      either Prochloperazine 0.1 - 0.2 mg kg(-1) or metoclopramide 0.1 - 0.2 mg kg(-1)
      can be safely administered as Prophylactic antiemetic till the availability of
      more efficacious and safe antiemetic drugs.

PMID- 16599034
TI  - Comparison of plasma viscosity and fibrinogen concentration in hypertensive and
      normotensive diabetics.
AB  - BACKGROUND: Body weight, body mass index, fibrinogen concentration and relative
      plasma viscosity can contribute to the development of hypertension in diabetics.
      This study compares body weight, body mass index, fibrinogen concentration and
      relative plasma viscosity between hypertensive diabetics, normotensive diabetics
      and healthy controls. METHODS: The present study was carried out on normotensive
      and hypertensive diabetics taken from medical OPD of Saidu group of teaching
      hospitals, Swat. A group of healthy male subjects between 30-60 years of age from
      the staff members of Saidu Medical College, Swat was also included. Each group
      comprised of 35 subjects. Systolic and diastolic blood pressures, body weight,
      height, body mass index, fibrinogen concentration and relative plasma viscosity
      were measured and compared. RESULTS: Body weight, body mass index, fibrinogen
      concentration and relative plasma viscosity were all significantly more in
      hypertensive diabetics than normotensive diabetics and healthy control subjects.
      CONCLUSION: The onset of the complications is different in the two groups of
      diabetics (hypertensive and normotensive), earlier in hypertensive diabetics and
      delayed in normotensive diabetics.

PMID- 16599035
TI  - Clinicopathological features of childhood visceral leishmaniasis in Azad Jammu &
      Kashmir Pakistan.
AB  - BACKGROUND: In Pakistan visceral leishmaniasis (VL) is endemic in Azad Jammu &
      Kashmir. Northern Areas and Northwest Frontier Province; the areas which lack
      adequate diagnostic facilities. This study describes the clinical and laboratory
      features in 61 cases of childhood VL. METHODS: All the children below 12 years of
      age who were managed as indoor cases from 1st Jan 1999 to 31st Dec 1999 were
      included in this study. The diagnosis of VL was established by demonstration of
      leishmania parasites in bone marrow aspiration. The demographic information,
      physical signs at presentations and results of complete blood picture and formol
      gel test were recorded. RESULTS: Median age of the patients was 18 months. Eighty
      four percent children were malnourished. Mean duration of fever before diagnosis
      was 45 days. Hepatosplenomegaly was present in all cases with mean enlargement of
      spleen and liver 6.8 and 3.2 cm respectively. Mean haemoglobin level. WBC and
      platelet counts were 6.7 g/dl, 4.8 x 109 /l and 70 x 109 /l respectively.
      Absolute neutrophil count was <1.5 x 109 /l in 61% cases. Mean reticulocyte count
      was 6.2%. There was significant negative correlation (p= 0.014) between
      haemoglobin level and spleen size. Formol gel test was positive in all cases.
      Mean hospital stay to established diagnosis was 8.6 days. CONCLUSION: The
      clinical and laboratory features of childhood VL in Azad Jammu and Kashmir are
      similar to Mediterranean type of disease caused by leishmania infantum. Cytopenia
      with high or normal reticulocyte count provides a useful clue to diagnosis in a
      febrile patient with hepatosplenomegally in an endemic area.

PMID- 16599036
TI  - Clinical presentation and management of visceral leishmaniasis.
AB  - BACKGROUND: Febrile illnesses like malaria, typhoid, and tuberculosis are the
      commonest problems in our area, but visceral leishmaniasis (VL) is also one of
      the diseases presenting with fever in this part of the country. This study was
      conducted to evaluate its clinical spectrum and way of management. METHODS: This
      study was conducted in Paediatric Department of Women and Children Hospital and
      Ayub Teaching Hospital, Abbottabad from October 1985 to August 1999 during which
      70 cases of VL were diagnosed and managed. RESULTS: All patients were below 10
      years of age and were from Hazara division. Majority of them were from two
      specific localities, one in Abbottabad District (43%) and the other in Mansehra
      District (14%). Common clinical features were Fever 99%, Splenomegaly (99%),
      Anaemia (96%), Hepatomegaly (86%), distension of abdomen (47%) and bleeding
      diathesis 14%. Haemoglobin was below 7.9 gm in 82.86%, white cell count was below
      4000/mm3 in 42.85%, Platelet count was below 100000/mm3 in 67.14% and ESR was >50
      mm at the end of first hour in 86% of the patients. All the patients showed
      Leishmania Donovani bodies in the bone marrow smears except one, where tap was
      dry and then trephine biopsy was performed to confirm the diagnosis. In 67 cases
      amastigote form was found and only in 3 patients the promastigotes were found.
      Fifty two patients had received meglumine antimoniate (glucantime) and 18
      received sodium stibogluconate (pentostam) along with supportive therapy.
      Mortality was 11.43%. CONCLUSIONS: The disease is gradually spreading southwards
      in the country. Children below 5 years are mainly affected. Bone marrow
      examination is the most reliable and simple method of diagnosis. A high index of
      suspicion must he kept in mind for all febrile cases coming from Hazara division,
      Northern areas, Azad Kashmir.

PMID- 16599037
TI  - Role of metformin in correcting hyperinsulinemia, menstrual irregularity and
      anovulation in polycystic ovary syndrome.
AB  - BACKGROUND: Previous studies suggest that metformin by reducing hyperinsulinemia
      is clinically useful in the treatment of polycystic ovary syndrome (PCOS). Our
      Objective was to observe the role of metformin in correcting
      oligomenorrhea/amenorrhea and anovulation within six month in hyperinsulinemic
      women with PCOS. Another aim was to assess the decrease in hyperinsulinemia and
      body weight by metformin in our population. METHODS: This study was carried out
      at the Department of Obstetrics and Gynaecology, Islamic International Medical
      Complex (IIMC) Islamabad, from October 2001 to March 2003. Fifty women fulfilling
      the clinical and biochemical criteria for PCOS and hyperinsulinemia were
      enrolled. Metformin was started at an oral dose of 500mg/day and maintained at
      1500mg for 6 months. Besides ultrasonography and body weight. serum FSH, LH,
      fasting insulin, fasting blood sugar and creatinine levels were performed. After
      six months menstrual cyclicity, fasting insulin levels, day 21 serum progesterone
      and body weights were assessed. RESULTS: After six months of Metformin therapy,
      menstrual regularity was achieved in 19 out of 22 women (86%). Out of these 11
      women (50%) were ovulating at six months. On Metformin, the median fasting serum
      insulin decreased from 23.6 micro U/ml to 20.2 micro U/ml (P<0.05). There was no
      significant weight reduction (p=0.096) with Metformin in six months. Data was
      analyzed using SPSS by paired t-test.

PMID- 16599038
TI  - Anticholinergic premedication for prevention of oculocardiac reflex during squint
      surgery.
AB  - BACKGROUND: Profound bradycardia during eye surgery is potentially serious event.
      In clinical practice this Oculocardiac Reflex (OCR) is most often encountered
      during squint surgery. The objective of this study was to assess the occurrence
      of OCR and prove the effect of anticholinergic premedication (atropine) to
      prevent OCR. METHODS: This study comprises of sixty patients (age 2-30 years)
      operated for squint surgery under general anaesthesia. Cases were divided into
      two groups of thirty each. Group 1 was premedicated with intravenous injection of
      atropine and Group 2 did not receive any premedication. Patients were monitored
      during operation for any bradycardia or dysrhythmias. RESULTS: The observed data
      showed occurrence of 70% OCR in Group 2 as compared to only 10% in Group 1.
      Severe bradycardia in 40% cases of Group 2 needed intervention by IV injection of
      atropine. CONCLUSION: Our study showed that atropine premedication in the
      patients of squint surgery under general anaesthesia definitely obtunds OCR and
      prevents any untoward effects of dysrhythmias during eye surgery.

PMID- 16599039
TI  - Secretion of calcium in the saliva of long-term tobacco users.
AB  - BACKGROUND: Secretion of calcium in saliva depends upon salivary flow rates in
      non-tobacco users and greater is the rate, lower is the concentration and vice
      versa. In long-term tobacco users the taste receptors, a primary site for
      salivary secretion, are constantly exposed to tobacco for long time thus
      presumably affecting the salivary reflex. Therefore the main purpose of the study
      was to study the secretion of calcium in the saliva of theses individuals.
      METHODS: Subjects of the study were divided into smokers, pan. (tobacco-betel
      lime "quid") chewers, niswar (moist oral snuff) dippers and non-tobacco users as
      controls. Each group was comprised of 20 healthy male adults. The saliva of each
      subject was collected under resting condition and following application of crude
      nicotine and citric acid solutions to the tip of his tongue. RESULTS: All groups
      of long-term tobacco users exhibited significantly higher concentrations of
      calcium before and after stimulation when compared with controls. However
      significant drop was observed in calcium levels of all groups including controls
      after stimulation but this drop was more pronounced after stimulation with citric
      acid than after stimulation with nicotine. CONCLUSION: We conclude that higher
      levels of calcium are present in the saliva of long-term tobacco users than non
      users which decreases as the flow of saliva increases.

PMID- 16599040
TI  - Release of vasopressin during suppression of oestrous cycle in rat by zoladex and
      hypovolemic challenge.
AB  - BACKGROUND: The vasopressin (AVP) response to hypovolemia has been compared in
      intact and chemically castrated rats. This functional ovariectomy was done to
      confirm the findings in surgical ovariectomy of how gonadal steroids modulate the
      release of AVP under hypo-volemic challenge. METHODS: Twenty female Sprague
      Dawley rats were checked for oestrous over two consecutive cycles. The ten
      control rats were given sub-cutaneous puncture only whereas the experimental were
      given Zoladex implant. On the fifteenth day all the rats were given intra
      peitoneal injection of poly-ehylene glycol. All the rats were de-capitated after
      an hour. RESULTS: The uterine weight was significantly decreased in experimental
      group. The plasma AVP level was also significantly decreased in the experimental
      group. The pituitary AVP level was significantly increased in the experimental
      group. CONCLUSION: The chemical castration effected the AVP secretion, this
      proves that the sex steroids modulate the release of AVP secretion inspite of
      hypo-volemic challenge.

PMID- 16599041
TI  - Temporomandibular joint ankylosis: experience with interpositional gap
      arthroplasty at Ayub Medical College Abbottabad.
AB  - BACKGROUND: Satisfactory surgical correction of temporomandibular joint ankylosis
      (TMA) is limited by a high recurrence rate, particularly in patients who
      underwent surgery without use of interpositional material. The present study
      describes our experience of Interpositional Gap Arthroplasty in patients
      presenting with primary or recurrent TMA. METHODS: The study was conducted on 12
      patients presenting at the Oral and Maxillo-Facial Surgical Unit of the Ayub
      Medical College Abbottabad from 1999 to 2004. Interpositioning materials used
      included Temporalis fascia, Temporalis muscle, Silastic sheet and Cartilage
      (Costochondral) graft. Pre- and Postoperative assessment of temporomandibular
      joint (TMJ) mobility was done by clinical assessment of jaw movement and
      measurement of interincisal distance by vernier calipers; X-rays were done to
      document complications such as fibrosis and ankylosis. RESULTS: Nine of the 12
      patients (75%) were new cases of ankylosis, while the remaining 3 (25%) had one,
      three and four prior operations. Duration of ankylosis ranged from 9 months to 12
      years. Ankylosis was bilateral in 8 cases (66.7%) and unilateral in 4 cases
      (33.3%). Operative findings were simple bony ankylosis in 13/20 jaws (65%), soft
      tissue fibrosis in 4/20 jaws (20%) and massive bony growth in 3/20 jaws (15%).
      Preoperative interincisal distances ranged from 0-15mm; immediate postoperative
      distances ranged from 20-40 mm; one-month and six-month postoperative distances
      ranged from 25-50 mm. All patients had an uncomplicated outcome till six months
      follow up; one patient developed reduced mouth opening to 12 mm at one year
      follow up due to parental noncompliance with mouth exercises; one patient
      developed infection and extrusion of silastic sheet at 2.5 years follow up.
      CONCLUSION: Interpositional Gap Arthroplasty is a highly effective and safe
      surgical management option for TMA with acceptable immediate and long term
      outcome, particularly when temporalis fascia and muscle are used for adults and
      costochondral grafts with fascia interposition used for children.

PMID- 16599042
TI  - Frequency and risk factors for wound dehiscence/burst abdomen in midline
      laparotomies.
AB  - BACKGROUND: Wound dehiscence/burst abdomen is a very serious postoperative
      complication associated with high morbidity and mortality. It has significant
      impact on health care cost, both for the patients and hospitals. The aim of the
      study was to determine the frequency of wound dehiscence/burst abdomen in
      patients undergoing emergency and elective laparotomies through midline incisions
      and to identify the risk factors for wound dehiscence. METHODS: This study was
      carried out at department of General Surgery, Pakistan Institute of Medical
      Sciences, Islamabad from 1st January 2002 to 31st December 2002. 117 consecutive
      patients undergoing laparotomy with midline incision were included. They were
      followed by wound examination from third postoperative day onwards to see their
      normal or otherwise healing. RESULTS: Seven out of 117 (5.9%) patients developed
      wound dehiscence. Five of them (4.2%) were operated in emergency and two (1.7%)
      were operated on elective list. CONCLUSION: It is very clear from our study that
      frequency of wound dehiscence/burst abdomen is still very high in our hospital.
      Peritonitis, wound infection and failure to close the abdominal wall properly are
      most important causes of wound dehiscence. Malnourishment and malignant
      obstructive jaundice predispose a patient to wound dehiscence by slowing the
      healing, and increasing rate of wound infection.

PMID- 16599043
TI  - Case report congenital LQTS--an electrocardiographic and genotype correlation.
AB  - The congenital Long QT Syndrome (LQTS) is characterized by abnormally prolonged
      ventricular repolarization due to inherited defect in cardiac sodium and
      potassium channels, which predisposes the patients to syncope, ventricular
      arrhythmias, and sudden cardiac death. Early diagnosis and preventive treatment
      are instrumental to prevent sudden cardiac death in patients with the congenital
      LQTS. The diagnostic criteria for congenital LQTS are based on certain
      electrocardiographic findings and clinical history. Recently genotype specific
      electrocardiographic pattern in the congenital LQTS has also been described.
      Recent studies suggest feasibility of genotype specific treatment of LQTS and in
      near future, mutation specific treatment will probably become a novel approach to
      this potentially fatal syndrome. We describe two cases that fulfilled the
      electrocardiographic and historical diagnostic criteria with morphology on
      electrocardiogram (ECG) suggestive of LQT1 genotype.

PMID- 16599044
TI  - Spontaneous fecal fistula: a rare presentation of inguinal hernia.
AB  - A 25 years old young man presented with the right scrotal and supra-pubic fecal
      fistulae due to the spontaneous bursting of a congenital inguinal hernia. This
      hernia remained obstructed and strangulated for about ten days before getting
      ruptured. Resection and end to end anastomosis of involved ileum was done. The
      literature search could reveal only five such cases in pediatric age group and
      this complication is considered to be much rarer among the adult population. This
      case report is being presented here in view of the extreme rarity of this
      complication in the adult age group.

PMID- 16599045
TI  - Typhoid fever and viral hepatitis in a G6PD deficient individual.
AB  - Simultaneous occurrence of multiple diseases is unusual but not rare. We are
      reporting an unusual combination of Typhoid fever and viral hepatitis in a G6PD
      deficient individual.

PMID- 16599046
TI  - Pre-operative pulmonary evaluation.
AB  - Postoperative pulmonary complications contribute significantly to morbidity and
      morality in surgical patients. Pulmonary complications occur more frequently than
      cardiac complications. The complication rates for upper abdominal and thoracic
      surgery are the highest. A better understanding of the risk factors associated
      with postoperative pulmonary complications is essential to develop strategies for
      reducing these complications. In any individual patient the benefit from a
      surgical procedure should be weighed against the risks it imposes. When possible,
      stabilization of respiratory status is advisable before surgery. This article
      reviews patient and procedure related risk factors, clinical and laboratory
      evaluation for preoperative risk assessment and risk reduction strategies to
      minimize the complication rates.

PMID- 16599047
TI  - Correlates of self-reported arthritis in adult Pakistani population.

PMID- 16599048
TI  - Neuraminidase antibody response to inactivated influenza virus vaccine following
      intranasal and intramuscular vaccination.
AB  - BACKGROUND: The evaluation of influenza vaccine activity and potency are based on
      the immune response to hemagglutinin, and protection is indicated when the titer
      of hemagglutination inhibition serum antibody is > or = 1:40. Neuraminidase, the
      second surface glycoprotein, may also have a role in protection, but little
      information is available on the immunologic response to this component.
      OBJECTIVES: To determine whether any response to neuraminidase is evoked by
      intranasal immunization with a novel, whole, inactivated anti-influenza vaccine.
      METHODS: This study was part of a more comprehensive study of mucosal and serum
      immune response to this vaccine. Fifty-four young adults were immunized
      intranasally, 9 intramuscularly and 18 received a placebo. Twenty-three elderly
      people were immunized intramuscularly, and 21 elderly and 17 children were
      immunized intranasally. Serum and nasal antibodies to antigens N1 and N2 were
      determined by the lectin neuraminidase test. RESULTS: Serum response following
      intranasal vaccination was lower than after intramuscular vaccination, and ranged
      from 21.4 to 35.3% and 33.3 to 64.7% following intranasal vaccination and from
      52.2 to 77.8% and 47.8 to 88.9% after intramuscular vaccination, to N1 and N2
      respectively. Nasal antibody response was low and was found only after intranasal
      vaccination, and response to N2 was better than to the N1 antigen. CONCLUSIONS:
      It may be beneficial if future vaccines would include competent hemagglutinin and
      neuraminidase, which would afford a higher level of protection.

PMID- 16599050
TI  - Adoptive cell therapy for metastatic melanoma patients: pre-clinical development
      at the Sheba Medical Center.
AB  - BACKGROUND: Metastatic melanoma is an aggressive and highly malignant cancer. The
      5 year survival rate of patients with metastatic disease is less than 5% with a
      median survival of only 6-10 months. Drugs like dacarbazin (DTIC) as a single
      agent or in combination with other chemotherapy agents have a response rate of 15
      30%, but the duration of response is usually short with no impact on survival.
      Interleukin-2-based immunotherapy has shown more promising results. The National
      Institutes of Health recently reported that lymphodepleting chemotherapy,
      followed by an adoptive transfer of large numbers of anti-tumor specific tumor
      infiltrating lymphocytes, resulted in an objective regression in 51% of patients.
      OBJECTIVES: To introduce the TIL technology to advanced metastatic melanoma
      patients in Israel. METHODS: We generated TIL cultures from tumor tissue,
      choosing those with specific activity against melanoma and expanding them to
      large numbers. RESULTS: TIL cultures from nine patients were established and
      examined for their specific activity against the patients' autologous tumor
      cells. Twelve TIL cultures derived from 5 different patients showed the desired
      anti-tumor activity, making those 5 patients potential candidates for the
      therapy. CONCLUSIONS: Pre-clinical studies of the TIL technology in a clinical
      laboratory set-up were performed successfully and this modality is ready for
      treating metastatic melanoma patients at the Sheba Medical Center's Ella
      Institute.

PMID- 16599049
TI  - Genetic analyses of non-small cell lung cancer in Jewish Israeli patients.
AB  - BACKGROUND: The contribution of the abnormal DNA mismatch repair system to non
      small cell lung cancer tumorigenesis is controversial and has not been reported
      in Jewish Israeli patients. Similarly, the involvement of 3p deletions in NSCLC
      in the same population has not been assessed. OBJECTIVES: To assess the
      contribution of the DNA-MMR system to NSCLC pathogenesis by analyzing
      microsatellite instability, and evaluate loss of heterozygosity at 3p rates in
      Israeli NSCLC patients. METHODS: Paired DNA from tumorous and non-tumorous tissue
      was extracted, and genotyping for MSI determination was carded out using the five
      Bethesda markers and for determining LOH two 3p markers were used. Genotyping was
      performed using polymerase chain reaction amplification and size separation on an
      ABI semiautomatic DNA sequencer, and the allelic patterns of tumorous and non
      tumorous tissue were compared. RESULTS: Forty-four NSCLCs from 35 smokers and 9
      non-smokers were analyzed, with 26 of the 44 (59%) at stage I disease. Using five
      microsatellite markers (D17S250, D5S346, D2S123, BAT-25, BAT-26) (known as
      Bethesda markers) for MSI determination, 6 of the 44 tumors (13.6%) exhibited MSI
      in at least one marker. Similarly, genotyping for LOH at chromosome 3p was
      performed using two markers (D3S4103, D3S1234) located at 3p14.2 I. With D3S4103,
      33 of the 44 patients successfully analyzed were homozygous and therefore non
      informative with respect to LOH. Using D3S1234, 33 of 36 patients (91.7%) were
      heterozygous, and 23 of these individuals' tumors (69.7%) displayed LOH.
      Unexpectedly, 4 of 33 tumors (12.1%) genotyped by D3S4103, and 16 of 36 tumors
      (44.5%) genotyped by D3S1234 showed a pattern of MSI, even though only one of
      these tumors showed a similar pattern when genotyped with the five consensus
      markers. Overall, 23 of 44 tumors (52.3%) demonstrated MSI on at least one
      marker, and 5 of these 23 tumors (21.7%) had MSI on two or more markers.
      CONCLUSIONS: MSI using 3p markers and not the Bethesda markers occurs at a high
      rate and in early stages in Jewish NSCLC patients.

PMID- 16599052
TI  - Laparoscopic implantation of the Tenckhoff catheter for the treatment of end
      stage renal failure and congestive heart failure: experience with the pelvic
      fixation technique.
AB  - BACKGROUND: Peritoneal dialysis is a widely accepted route for renal replacement.
      With the advent of endoscopy, many surgical techniques for the prevention of
      catheter failure have been proposed. OBJECTIVES: To evaluate the outcomes of
      patients undergoing laparoscopic Tenckhoff catheter implantation using the pelvic
      fixation technique. METHODS: Data analysis was retrospective. All procedures were
      performed under general anesthesia. A double-cuffed catheter was inserted using
      two 5 mm trocars and one 10 mm trocar, fixing its internal tip to the dome of the
      bladder and its inner cuff to the fascia. Catheter failure was defined as
      persistent peritonitis/exit-site/tunnel infection, severe dialysate leak,
      migration or outflow obstruction. RESULTS: LTCI was performed in 34 patients.
      Mean patient age was 65 +/- 17 years. In 12 of the 34 patients the indication for
      LTCI was end-stage renal failure combined with NYHA class IV congestive heart
      failure. Operative time was 35 +/- 15 minutes. A previous laparotomy was
      performed in 9 patients. Hospital stay was 1.5 +/- 0.6 days. The first continuous
      ambulatory peritoneal dialysis was performed after 20 +/- 12 days. Median follow
      up time was 13 months. There were several complications, including 5 (14%) exit
      site/tunnel infections, 27 episodes (0.05 per patient-month) of bacterial
      peritonitis, 3 (9%) incisional hernias, 1 case of fatal intraabdominal bleeding,
      2 (5.8%) catheter migrations (functionally significant), and 10 (30%) cases of
      catheter plugging, 8 of which were treated successfully by instillation of
      urokinase and 2 surgically. A complication-mandated surgery was performed in 8
      patients (23.5%). The 1 year failure-free rate of the catheter was 80.8%. One
      fatal intraabdominal bleeding was recorded. CONCLUSIONS: LTCI is safe, obviating
      the need for laparotomy in high risk patients. Catheter fixation to the bladder
      may prevent common mechanical failures.

PMID- 16599051
TI  - Hypertonic saline/epinephrine treatment in hospitalized infants with viral
      bronchiolitis reduces hospitalization stay: 2 years experience.
AB  - BACKGROUND: We recently published preliminary evidence on the effectiveness of
      hypertonic saline in infants with viral bronchiolitis. OBJECTIVE: To further
      establish the efficacy of nebulized hypertonic saline in these infants. METHODS:
      In a continuing, second-year randomized, doubleblind controlled trial, an
      additional 41 infants (age 2.6 +/- 1 months) hospitalized with viral
      bronchiolitis were recruited during the winter of 2001-2002. The infants received
      inhalation of 1.5 mg epinephrine dissolved either in 4 ml normal (0.9%) saline
      (Group I, n=20) or 4 ml hypertonic (3%) saline (Group II, n=22). The therapy was
      repeated three times daily until discharge. Pooling our 2 years of experience
      (2000-2002), a total of 93 hospitalized infants with viral bronchiolitis were
      recruited; 45 were assigned to Group I and 48 to Group II. RESULTS: The clinical
      scores at baseline were 7.6 +/- 0.7 for Group I vs. 7.4 +/- 1.3 for Group II (P =
      NS). However, the clinical scores at days 1 and 2 after inhalation differed
      significantly between the two groups, invariably favoring Group II: 7 +/- 1 vs.
      6.25 +/- 1.1 (P< 0.05), 6.45 +/- 1 vs. 5.35 +/- 1.35 (P< 0.05), respectively.
      Adding aerosolized 3% saline to 1.5 mg epinephrine reduced the hospitalization
      stay from 3.5 +/- 1.7 days in Group I to 2.6 +/- 1.4 in Group II (P< 0.05). The
      pooled data of both years revealed that adding 3% saline to the inhalation
      mixture decreased hospitalization stay from 3.6 +/- 1.6 to 2.8 +/- 1.3 days (P<
      0.05). CONCLUSIONS: This second-year experience and our 2 year pooled data
      analysis strengthen the evidence that the combination of 3% saline/1.5 mg
      epinephrine benefits hospitalized infants with viral bronchiolitis.

PMID- 16599053
TI  - Survey of a pediatric hospital staff regarding cases of suspected child abuse and
      neglect.
AB  - BACKGROUND: The suspicion of child abuse and neglect may arise from
      manifestations such as physical or psychosomatic symptoms, eating disorders,
      suicidal behavior, impaired parental functioning, etc. Thus the arrival of an
      abused or neglected child at the hospital provides an opportunity for detecting
      the problem and beginning a process of change. Optimal utilization of this
      potential depends on the awareness, diagnostic ability and cooperation of the
      staff. OBJECTIVES: To assess knowledge about hospital policy, attitudes and
      actual behavior of hospital staff in cases of SCAN. METHODS: The questionnaire
      was adapted and distributed to a convenience sample of personnel at a children's
      hospital. The questionnaire included items on knowledge of hospital policy
      regarding SCAN, attitudes towards inquiring about cases that appear suspicious,
      and behaviors in cases in which the respondent was involved. The comparison of
      responses to specific questions and among members of different professions was
      analyzed by chi-square test. RESULTS: Eighty-two staff members completed the
      questionnaires. Most of the respondents were aware of hospital policy regarding
      suspected abuse (86.6%), with fewer regarding suspected neglect (77.2%).
      Physicians were the least aware of these policies, as compared to medical
      students, nurses and social workers. Although most considered the issue of SCAN a
      responsibility of members of their own profession, 35.4% considered it primarily
      the responsibility of the welfare or judicial systems. Over 40% felt
      uncomfortable discussing suspicions with the child and nearly half felt
      uncomfortable discussing them with parents. The most often reported reason for
      this was the sense that they lacked skills or training for dealing with the
      issue. Despite this, when asked about actual behavior, 94.7% responded that they
      do try to clarify the circumstances related to the suspicious symptoms.
      Respondents were more likely to contact the hospital social worker than community
      resources (91.5% vs. 47.2%). CONCLUSIONS: There is a need to encourage awareness,
      discourse and training of medical personnel regarding SCAN in order to maximize
      their potential to identify children at risk.

PMID- 16599055
TI  - Skin substitutes.
AB  - The role of skin substitutes in burn surgery and in the treatment of chronic
      wounds is constantly evolving. New products are regularly being developed and
      approved for clinical use. Studies on existing products demonstrate their
      effectiveness in different clinical scenarios. However, cost-related concerns,
      inadequate physician education, and the drawbacks that still accompany every skin
      substitute have resulted in limited application of these modalities. Today, burn
      surgeons still rely mostly on old-fashioned skin grafts. Only a few burn centers
      in the world actually use some of these products in their routine treatment of
      wounds. This review provides an up-to-date overview of the latest developments in
      the field of skin substitutes. We examine the major commercially available skin
      substitute products and their performance, and briefly review the technologies
      and products that are under development but have not yet become widely available.

PMID- 16599054
TI  - Use of complementary and alternative medicine among patients attending
      rheumatology clinics in Israel.
AB  - BACKGROUND: Complementary and alternative medicine has recently attracted
      attention due to its widespread use. In a recent study in Israel, almost a half
      of CAM users in the general population used it for joint diseases or back pain.
      OBJECTIVE: To evaluate the prevalence of CAM use among patients with defined
      rheumatic diseases, and analyze the demographic features of CAM users, their
      reasons for using CAM and the use of specific CAM methods. METHODS: We conducted
      face-to-face structured interviews of 350 patients attending rheumatology
      clinics, regarding past or present use of CAM, specifying the various CAM types
      they used, and reasons for using CAM. Demographic data including age, gender,
      country of birth and origin, and level of education were also collected. RESULTS:
      Altogether, 148 patients reported using CAM (42%). In general, homeopathy and
      acupuncture were the most commonly used types (44% and 41% of the patients,
      respectively). The mean number of CAM methods per patient was 1.9 +/- 1.1. CAM
      was more commonly used by patients with advanced education (52% vs. 37% of
      patients with lower education, P= 0.007). Patients with rheumatoid arthritis used
      CAM significantly less than patients with other rheumatologic conditions (32% vs.
      48%, P= 0.008). CONCLUSION: CAM use is influenced by level of education. The
      choice of the preferred CAM method among patients with rheumatic diseases seemed
      to follow the popular CAM methods in the general population, and was not specific
      to rheumatic diseases.

PMID- 16599056
TI  - Endometrial polyps in reproductive-age fertile and infertile women.
AB  - Endometrial polyps are a frequent finding in infertile patients. Little is known
      about the true prevalence of polyps in infertile patients. It is unproved whether
      polyps are causative of infertility, or whether surgical polypectomy by
      hysteroscopy improves the likelihood of successful conception. This article
      reviews endometrial polyps in reproductive-age fertile and infertile women.

PMID- 16599057
TI  - Recommendations for the treatment of scabies infestations in Israel.

PMID- 16599058
TI  - The neglect of "child abuse and neglect".

PMID- 16599059
TI  - Use of complementary and alternative medicine by rheumatology patients.

PMID- 16599060
TI  - Epstein-Barr virus-associated post-transplant lymphoproliferative disorder.

PMID- 16599061
TI  - Regenerating the heart using human embryonic stem cells--from cell to bedside.
AB  - The adult human heart has limited regenerative capacity and, therefore,
      functional restoration of the damaged heart presents a great challenge. Despite
      the progress achieved in the pharmacological and surgical treatment of
      degenerative myocardial diseases, they are still considered a major cause of
      morbidity and mortality in the western world. Repopulation of the damaged heart
      with cardiomyocytes represents a novel conceptual therapeutic paradigm but is
      hampered by the lack of sources for human cardiomyocytes. The recent derivation
      of pluripotent human embryonic stem cell lines may provide a solution for this
      cell sourcing problem. This review will focus on the derivation of the hESC
      lines, their mechanism of self-renewal, and their differentiation to
      cardiomyocytes. The possible signals and cues involved in the commitment and
      early differentiation of cardiomyocytes in this model will be discussed as well
      as the molecular, structural and electrophysiologic characteristics of the
      generated hESC-derived cardiomyocytes. Finally, the hurdles and challenges toward
      fully harnessing the potential clinical applications of these unique cells will
      be described.

PMID- 16599062
TI  - Upper airway manifestations of post-transplantation lymphoproliferative disease
      simulating common pediatric conditions.

PMID- 16599063
TI  - Graves' disease presenting as right heart failure.

PMID- 16599064
TI  - Postpartum hepatic rupture and retroperitoneal hematoma associated with HELLP
      syndrome.

PMID- 16599065
TI  - Rupture of an abdominal aortic aneurysm previously repaired with an endovascular
      stent-graft: successful management using an endovascular approach.

PMID- 16599066
TI  - Heart transplantation in females: the experience in Puerto Rico.
AB  - BACKGROUND: Heart transplantation is the procedure of choice for a selected group
      of patients with end stage heart disease. Gender related differences have been
      observed in the heart transplant field: less women than men are recipients of
      heart transplants, more risk of rejection in female recipients, and a perception
      toward reduced survival in women. We report our experience of heart
      transplantation in females in Puerto Rico. METHODS: We studied the data bank of
      69 heart transplant recipients in the Puerto Rico Heart Transplant Program from
      June 1999 to June 2005. Gender related differences in the number of recipients:
      males or females, incidence of rejection, survival, and other outcomes were
      analyzed. RESULTS: 69 patients received an orthotopic heart transplant from June
      1999 to June 2005, in a single center in Puerto Rico. The mean age of the
      patients was 47 (11-62) years. Fifty patients (72%) were men, and 19 patients
      (28%), were women. Survival in the female group at 3 months, 1, 2, 3, 4, and 5
      years was 100%, 100%, 100%, 100%, 90%, and 90% respectively. The survival in the
      male group at 3 months, 1, 2, 3, 4 and 5 years was 97%, 97%, 97%, 94%, 86 and 79%
      respectively. There was an early, higher incidence of rejection in women during
      the first three months post transplant; 1.5 vs. 0.75, (P=0.04) episodes per
      patient in the female, and male group respectively. After the third month post
      transplant there was no significant difference in rejection incidence. The
      incidence of infectious episodes was significantly more frequent in female than
      in male recipients, 2.8 vs. 1 (P=0.02) per patient respectively. CONCLUSIONS:
      There were more male than female heart transplant recipients at a ratio of 3:1,
      without a significant gender difference in survival. The risk of rejection was
      higher in females in the early period post transplantation, but thereafter this
      risk showed no signinificant statistical difference. The incidence of infection
      was more frequent in female than in male recipients.

PMID- 16599067
TI  - Prevalence of cardiovascular conditions and health services utilization in Puerto
      Rico, 2001.
AB  - OBJECTIVE To study the prevalence of cardiovascular conditions and health
      services utilization in Puerto Rico, 2001. METHODS All medical claims for
      coronary heart disease (ICD-9 410-414), hypertension (ICD-9 401-405), congestive
      heart failure (ICD-9 428) and cerebrovascular accidents and transient ischemia
      (ICD-9:430-438.9) submitted for reimbursement purposes to an insurance company
      (private and public sector) in Puerto Rico in 2001 were identified. Prevalence
      and medical care utilization concerning cardiovascular conditions was estimated
      with 95% confidence. RESULTS Overall prevalence of cardiovascular conditions was
      13.5% (95% CI: 11.68%-15.44%), being larger in the private sector (16.0%; 95% CI:
      15.98%-16.08% vs. 11.7%; 95% CI: 11.62%-11.77%). Although in both sectors
      prevalence increased with age, at same age groups was two times higher in the
      private sector. Hypertension was the most prevalent condition (9.7; 95% CI: 8.14%
      11.41%) being higher in females (10.4; 95% CI: 10.37%-10.51%) than in males (8.9;
      95% CI: 8.81%-8.96%). The health service utilization (physician's office visits,
      emergency room visits, and hospital admissions) was higher in males. However, it
      varies by sectors. CONCLUSIONS Significant difference exists in the prevalence of
      cardiovascular conditions and health services utilization among private and
      public sectors in Puerto Rico. The observed differences among the private and
      public populations imply that there are factors such as socioeconomic status,
      education, lifestyles, environmental hazards in neighborhoods, and health habits
      that could be involved in the differences.

PMID- 16599068
TI  - The metabolic syndrome and its cardiovascular manifestations.
AB  - The metabolic syndrome is one of the most discussed topics in the past 15 years.
      It is a collection of risk factors that includes insulin resistance, central
      obesity, arterial hypertension, and atherogenic dyslipidemia. The presence of
      these risk factors increases the probability of developing diabetes mellitus and
      cardiovascular disease, increasing coronary and cardiovascular mortality. The
      prevalence of the metabolic syndrome in the US has increased in the past years
      due to an increased incidence of obesity and physical inactivity. Diagnosis of
      the metabolic syndrome can be done with the use of established criteria by the
      NCEP-ATP III and the WHO. The principal treatment for this condition is to modify
      life styles, most importantly, diet and exercise. In many cases, this
      intervention alone is not sufficient to control these risk factors and a more
      aggressive intervention is required, including drugs directed to each risk factor
      independently to avoid complications due to the development of cardiovascular
      disease associated to the syndrome.

PMID- 16599069
TI  - Mitral valvular heart disease in the adults.
AB  - Valvular Heart Disease (VHD) is an important cardiovascular problem in the adult
      population. The knowledge of the physiology involved, prompt recognition and
      diagnosis are of paramount importance for the primary care physician who is in
      the front line of patient care. This article is the first of a series of two that
      will discuss valvular problems in the adults in concise and practical form. Each
      topic will be presented using the following format: description, etiology,
      pathophysiology, natural history, essential of diagnosis and management. In this
      first article we will discuss mitral valve disorders including mitral valve
      prolapse (MVP).

PMID- 16599070
TI  - Evaluation of cardiovascular risks for non cardiac surgery.
AB  - Physicians are frequently concerned with the management of the surgical risk in
      patients with heart disease requiring non cardiac surgery. A preoperative
      evaluation helps to assess the cardiac risk for the planned surgery and helps to
      take measures to reduce that risk. We summarize the essentials in evaluating
      patients with coronary artery disease, valvular heart disease, arterial
      hypertension, arrhythmias, permanent pacemaker bearers, and those with congestive
      heart failure in order to prevent cardiac complications during the required
      surgery. Special attention has been given to the functional capacity, cardiac
      risk present, presence or absence of left ventricular dysfunction and the
      institution of protective measures. The usefulness of the ACC AHA guidelines has
      been summarized.

PMID- 16599071
TI  - Percutaneous coronary intervention versus thrombolysis: the definite management
      of st elevation myocardial infarction.
AB  - The management of an ST elevation myocardial infarction has undergone significant
      changes in the past few years. Fibrinolytic agents have become more and more clot
      specific increasing their efficacy. However, percutaneous coronary intervention,
      along with its adjuvant therapy (glycoprotein IIB/IIIA receptor inhibitors and
      clopidrogel), have come to challenge fibrinolytic use. Many studies have
      demonstrated the benefits of percutaneous coronary intervention as compared to
      fibrinolysis in the management of acute myocardial infarction by decreasing
      infarct size, myocardial function loss, and mortality.

PMID- 16599072
TI  - Carbon monoxide toxicity with neurological and cardiac complications.
AB  - A family suffered carbon monoxide toxicity, with cerebral and / or cardiac
      complications, while sleeping in the cabin on a recreational boat. This article
      describes a couple exposed to a malfunctioning air-conditioning system on the
      boat, which subsequently developed the unique combination of cerebral symptoms
      and a non Q/non-ST elevation myocardial infarction, with enzyme elevations and
      electrocardiographic abnormalities. This interesting complication of a myocardial
      infarction secondary to carbon monoxide toxicity, associated with neurological
      manifestations, is reviewed.

PMID- 16599073
TI  - Bilobulated atrial myxoma originating from low interatrial septum.
AB  - Myxomas are the most common type of primary cardiac tumors. Around 70% of
      patients who have them are females, 86% occur in the left atrium and more than
      90% are solitary. In the left atrium the usual site of attachment is in the fossa
      ovalis. Less common sites within the left atrium are the mitral valve or in areas
      near it. This patient, with a left atrial myxoma originating low in the
      interatrial septum near the mitral valve, is one of the first cases reported in
      Puerto Rico. The patient is a 41 year old female with no previous history of
      systemic illnesses who one month prior to admission developed episodes of chest
      pain and shortness of breath. A 2D echo, done by a local physician, revealed a
      mobile left atrial mass causing diastolic obstruction of the valve. She was
      referred to our institution for further evaluation. A transesophageal echo was
      done showing a large bilobulated mass connected to the lowermost portion of the
      atrial septum, close to the mitral annulus, specially to the anterior leaflet. It
      also showed concurrent mitral regurgitation caused by the mass. The tumor was
      successfully resected without major complications and it was proven to be
      connected to the septum 1 cm above the mitral annulus. Pathological examination
      confirmed it to be a myxoma.

PMID- 16599074
TI  - Primary pulmonary hypertension and pregnancy.
AB  - Primary pulmonary hypertension (PPH) is a disorder intrinsic to the pulmonary
      vascular bed characterized by sustained elevation in pulmonary artery pressure
      and pulmonary vascular resistance with normal pulmonary artery wedge pressure, in
      the absence of a known cause. Cardiovascular disorders are the most common cause
      of morbidity and mortality in pregnant women. Risk is so great with some
      cardiovascular abnor-malities that recommendation of avoidance or interruption of
      pregnancy is supportable, one of these conditions is pulmonary hypertension. In
      this article two patients with primary pulmonary hypertension who sustained two
      pregnancies each are described. Both patients had uneventful pregnancies and
      deliveries, with all neonates surviving. When evaluating primary pulmonary
      hypertension and pregnancy, early studies reported a maternal mortality rate as
      high as 50%. More recent studies report a maternal mortality of 30%. In this
      article, cases of primary pulmonary hypertension undergoing pregnancy from 1978
      to 2005 were reviewed, revealing a 22% maternal mortality for the total number of
      pregnancies. Despite advances in treatment, primary pulmonary hypertension
      continues to carry considerable maternal morbidity and mortality, and prevention
      of pregnancy is still the main recommendation. Early diagnosis and treatment is
      critical and a multi-disciplinary approach is required when dealing with a
      patient with PPH who desires to continue pregnancy.

PMID- 16599075
TI  - Aged care is a challenging career.

PMID- 16599076
TI  - 'Blatant' political campaigning critcised.

PMID- 16599077
TI  - Truth-telling important in nursing.

PMID- 16599078
TI  - Maori leader's message disheartening.

PMID- 16599079
TI  - Congratulations for education article.

PMID- 16599080
TI  - Where have the 'hands-on' skills gone?

PMID- 16599081
TI  - US theatre milieu completely different.

PMID- 16599082
TI  - Researching children's mental health.

PMID- 16599083
TI  - Coping with outbreaks of the norovirus.

PMID- 16599084
TI  - Nursing older people--a role for new graduates?

PMID- 16599085
TI  - Bringing the 'healing touch of human sympathy' into aged care.

PMID- 16599086
TI  - How caregivers respond to aged-care residents' aggressive behaviour.

PMID- 16599087
TI  - A passion for aged care.

PMID- 16599088
TI  - Looking back on nursing and four life-long friendships.

PMID- 16599089
TI  - How to solve problems in the aged-care sector.

PMID- 16599090
TI  - Effect of five staining solutions on the colour stability of two acrylics and
      three composite resins based provisional restorations.
AB  - The effect of coffee, tea, coca-cola, orange-juice and red wine on the colour
      stability of acrylic and composite based provisional materials were evaluated.
      Two acrylic resins and three composite resins were studied. 48 standardized
      specimens for each provisional material were prepared. Each group was divided
      into 6 subgroups. Specimens from each group were immersed in staining solutions
      at room temperature for 30 days. Red wine and tea caused the most significant
      colour changes and orange juice showed the least significant colour changes.
      deltaE of all of the provisional restorations materials was changed after the
      immersion in all of the staining solutions during the experimental process.

PMID- 16599091
TI  - Surface microhardness of a resin composite: a comparison of a tungsten halogen
      and a LED light curing unit, in vitro.
AB  - A comparison has been made between published surface microhardness numbers (VHN)
      of a commercial resin composite for different exposure times to a quartz tungsten
      halogen (QTH) and light-emitting diode (LED) light-curing unit (LCU). Both LCUs
      produced comparable hardness at both top and bottom surfaces, respectively, and
      similar bottom/top hardness ratios, for a specimen thickness of 1.5 mm, given
      sufficient exposure time (40 s) and an elapsed time of 24 h before measurement
      (for hardness numbers). However, some data are significantly different. There is
      no advantage in either LCU regarding optimal hardness and hardness ratios given
      an appropriate protocol. Immediate finishing (1 h) was more appropriate to the
      use of the LED LCU (with adequate exposure time). The effect of elapsed time
      after exposure on microhardness was more pronounced with the QTH LCU.

PMID- 16599092
TI  - Partial edentulism and removable denture construction: a frequency study in
      Jordanians.
AB  - This study aimed to investigate the frequency of different classes of patterns of
      partial edentulism and the most frequently used design components of conventional
      cobalt-chromium RPD constructed for patients attending a dental teaching hospital
      in Jordan. Two- hundred laboratory authorization forms were reviewed. Of the
      total 200 patients (150 male, 48 females, mean age 44.5 years), 150 patients had
      both maxillary and mandibular Co-Cr RPDs constructed with a total number of
      frameworks sums to 350. Kennedy classification was followed to identify the class
      of partial edentulism. Of the total 350 patterns, Kennedy class III was the most
      common classification encountered in maxilla (47%) and in the mandible (45%).
      Among combinations, maxillary Kennedy class III classification opposing
      mandibular class III was the most common combination (30%). The lingual bar was
      the most frequently designed major connector (77%), while palatal strap was the
      most common connector in the maxilla (38%). Significantly (p<0.05), patterns with
      Kennedy class II and III were more frequent among males than females. The most
      common type of direct retainer used was the circumferential clasp in both
      maxillary and mandibular RPD's. On the other hand, ring clasps were used three
      times more frequently in mandibular RPD frameworks compared to maxillary RPD's.
      The RPI clasp assembly was used in class I and class II situations in 75% of
      cases more common in the mandible. It is concluded that the variations in
      construction of RPD design concepts with international studies reflects the
      influence of teaching philosophy and diversity of faculty members' backgrounds.

PMID- 16599093
TI  - Bond strength of luting cement to casting and soldering alloy.
AB  - Adjustment of metal alloy framework of the porcelain-fused-to-metal crown by
      soldering minor marginal deficiences prior insertion may sometimes be needed. The
      aim of this study was to compare shear bond strengths of four luting cements to
      casting metal alloy and soldering metal alloy. A total of 64 flame cast non
      precious metal alloy and flame soldered metal alloy samples were used. Durelon,
      Panavia F, RelyX Unicem Applicap and RelyX ARC stubs were bonded to the alloy
      substrate surface. After stored in water at 37 degrees C for 1 week, shear bond
      strength of the cement to the alloy was measured. Differences were analyzed using
      one way ANOVA (p<0.05). There were no difference between the cast metal alloy and
      soldering metal alloy substrate.

PMID- 16599094
TI  - Film thickness and rheological properties of luting agents for crown cementation.
AB  - The film thickness and rheological properties [viscosity and tan sigma], of
      different resin based crown and bridge luting agents, including Panavia 21,
      Superbond, All Bond C&B Cement, Variolink were compared with zinc phosphate
      cement. A modification of the method in ISO 9917 (1991) and a controlled stress
      rheometer were used to monitor the changes in the film thickness and rheological
      properties respectively. For each material, the film thickness and rheological
      characteristics were determined at 60s after start of mixing and then made at
      regular intervals until immediately before the material was set. For the initial
      film thickness, the difference among the values for Varionk, Superbond and zinc
      phosphate cement was not significant (P>0.05), and less than 25microm. The values
      for All Bond C&B Cement and Panavia 21 were at least twice that of the other
      materials tested. All Bond C&B Cement produced the highest film thickness value
      at both the initial period and at 240s. Regarding viscosity, Superbond had the
      lowest initial value but the highest value at 240s. Variolink gave the highest
      initial value of viscosity, but the differences in the initial values among the
      other materials were small. During the whole period of testing, zinc phosphate
      cement gave the highest values of tan sigma, and Panavia 21 showed no significant
      change in any of the measured properties. The methods were able to distinguish
      the behaviour of different cement materials. Some resin cements produce larger
      than optimal values of film thickness and in some cases this is related to a
      rapid increase in viscosity after mixing. It is expected that differences in the
      ability of cements to form thin films will affect the seating of cemented
      restorations.

PMID- 16599095
TI  - The effect of cooking method upon the titratable acidity of a popular vegetarian
      dish--scope for reducing its erosive potential?
AB  - The purpose of this in vitro study was to determine the effect of cooking method
      on the erosive potential of ratatouille. Two cooking methods, stewing and oven
      roasting, were applied to standardised ingredients taken from the same fruits and
      vegetables. The resultant dishes were liquidised and diluted with 100 mls of
      distilled water. Five 25 ml samples of each group were titrated to pH 7.0 against
      0.1 Molar Sodium Hydroxide. In order to ascertain the relative contribution of
      each ingredient each was singly prepared and cooked by stewing or oven roasting
      following the same quantities and dilutions as for the dish as a whole. 25 ml
      samples of these were titrated to pH 7.0 against 0.1 Molar Sodium Hydroxide. For
      ratatouille as a dish significantly (P < 0.0001) more alkali had to be added to
      the oven roast group (Mean = 8.60 mls, S.D. = 0.31) than to the stewed group
      (Mean = 3.92 mls, S.D. = 0.50) in order to bring about neutrality. Oven roasting
      of ingredients significantly (P < 0.001) lowered the initial pH with the
      exceptions of tomatoes and red peppers. Stewing reduced the volume of alkali
      required to neutralise aubergine (P < 0.001), green peppers (P < 0.001) and
      courgettes (P < 0.05). Significantly (P < 0.001) more alkali however was required
      to neutralise stewed red pepper. It was concluded that the method of cooking
      identical ingredients affects the erosive potential of ratatouille. Although oven
      roasting results in a higher erosive potential of ratatouille compared to stewing
      the method of cooking, at an individual ingredient level, does not have a
      universal effect upon erosive potential as determined by titratable acidity. This
      should be borne in mind when advising patients.

PMID- 16599096
TI  - Variability of centric relation position in TMD patients.
AB  - Reproducibility of the centric relation position for patients with
      temporomandibular disorders (TMD) is not documented in the current literature. It
      was the objective of this study to assess clinical variability of the centric
      relation position for TMD patients with a muscle-determined technique by means of
      an anterior deprogramming device, the leaf gauge. A sample of 60 patients with
      signs of TMD was selected, 8 men (Mean age 28,6, SD 5,2) and 52 women (Mean age
      30,5, SD 10,1). All patients were examined with the Research Diagnostic Criteria,
      including pain on movement and/or function, mouth opening, joint sounds and
      palpation of masticatory muscles. All 60 patients were allocated to one of the
      following diagnostic subgroups: myofascial pain, disk displacement with
      reduction, disk displacement without reduction, osteoarthritis, trauma. Twelve
      control subjects were taken from a previous study. Three sequential centric
      relation records were taken; the first one was used to mount a set of casts to an
      articulator. Criteria of precision were formulated beforehand: 2 out of 3 centric
      relation records had to be identical in a split-cast procedure. Variables XL and
      XR represented mandibular displacement in the sagittal plane, variables YL and YR
      in the transversal plane, and ZL and ZR in the vertical plane, on the left and
      right condylar level respectively. Variables XMIN, YMIN and ZMIN represented the
      minimal sagittal, transversal and vertical displacement left or right
      respectively. Likewise, variables XMAX, YMAX and ZMAX represented the maximal
      sagittal, transversal and vertical displacement left or right. XDIFF, YDIFF and
      ZDIFF represented the difference between the minimal and maximal values of X, Y
      and Z. The diagnostic subgroup trauma was excluded, because there was only one
      patient. The null-hypothesis of no between-group differences in within-subject
      and total variability was tested with an analysis of variance (ANOVA). The level
      of significance was set at 0.05. To minimize type I errors caused by multiple
      testing Scheffe's test was used to maintain an overall significance of 0.05. No
      significant difference between patients and control subjects could be found for
      variables XL, XR, YL, YR, ZR and ZL. Variables XMIN, YMIN, ZMIN, XMAX, YMAX,
      ZMAX, XDIFF, YDIFF and ZDIFF showed no significant differences. Scheffe's testing
      for the variables XL, XR, YL, YR, ZL and ZR, as well as the variables XMIN, YMIN,
      ZMIN, XMAX, YMAX, ZMAX, XDIFF YDIFF and ZDIFF showed no significant differences.
      The results of this study suggest no variability in centric relation position
      between TMD-patients and control subjects by means of the leaf gauge.

PMID- 16599097
TI  - Comparison of two topical treatments for dentine sensitivity.
AB  - This study compares two commercially-available products for treating dentine
      sensitivity, Duraphat, a fluoride varnish, and SuperSeal, an oxalate preparation.
      48 patients with dentine sensitivity were recruited. Sensitivity was assessed by
      visual analogue scales (VAS) to record pain following stimulation of exposed
      dentine surfaces by tactile stimulus (sharp probe at 60g force), thermal stimulus
      (ethyl chloride) and evaporative stimulus (air drying). Patients were randomised
      to treatment with either Duraphat or SuperSeal. After 4 weeks, sensitivity
      assessments were repeated. Both treatments resulted in statistically significant
      reductions in VAS scores for all stimuli (P<0.05). However, analysis of
      covariance failed to identify statistically significant differences in the
      magnitude of reductions in sensitivity achieved by each of the products (P>0.05).
      The treatments had similar efficacy and both can be considered effective
      therapies for treating dentine sensitivity.

PMID- 16599098
TI  - Recording surface detail on moist surfaces with elastomeric impression materials.
AB  - The objective was to assess the ability to accurately record detail on moist
      surfaces for three elastomeric impression materials derived from different
      polymers. One polyvinylsiloxane, one polyether and one hybrid material containing
      a copolymer of siloxane and polyether polymers were used. Impressions were
      recorded of moist gypsum casts having both a shallow (approximately 20 microm)
      and deep (approximately 180 microm) groove reproduced on their surface. The
      grooves in the casts and in the impressions were profiled using a non-contacting
      laser profilometer Comparisons were made between the groove depths in the casts
      and impressions (paired t-test). The results indicated that all of the tested
      materials accurately recorded dimensions in the x-y plane. However, there was
      evidence that the polyether and hybrid materials were more accurate than the
      polyvinylsiloxane in recording the true depths of the deep grooves (z plane)
      under moist conditions. It was concluded that the more hydrophilic nature of the
      polyether and hybrid materials enabled them to record more accurate impressions
      of moist surfaces, particularly in areas of difficult access as modelled by the
      deep grooves.

PMID- 16599099
TI  - Importance of Escherichia coli strains producing verotoxins.

PMID- 16599100
TI  - Antibodies among healthy population of developing countries against
      enterohaemorrhagic Escherichia coli O157:H7.
AB  - In Thailand, no reports are available on Escherichia coli serotype O157:H7, a
      causative agent of severe bloody diarrhoea, sometimes associated with haemolytic
      uraemic syndrome and thrombotic thrombocytopenic purpura. The reason for the non
      identification of infection due to E. coli O157 in this country and in other
      developing countries has not been rigorously discussed. The aim of this study was
      to determine the humoral response against the infectious organism. The IgM and
      IgG antibody responses against E. coli O157 lipopolysaccharide were studied using
      indirect enzyme-linked immunosorbent assay. Three hundred and thirty-two serum
      samples obtained from healthy blood donors and patients with diseases unrelated
      to diarrhoea were investigated. With a cut-off value of mean +2 SDs for each age
      group, the frequency of the IgM and IgG responses to O157 lipopolysaccharide was
      11.74% (39 of 332 samples) and 22.59% (75 of 332 samples) respectively.
      Furthermore, agglutination test of 173 subjects revealed titres ranging from 10
      to 40 in all the samples. The results suggest possible exposure of the Thai
      population to cross-reacting antigens from other intestinal organisms in addition
      to infection due to E. coli O157:H7.

PMID- 16599101
TI  - Initiation of zinc treatment for acute childhood diarrhoea and risk for vomiting
      or regurgitation: a randomized, double-blind, placebo-controlled trial.
AB  - The childhood diarrhoea-management guidelines of the World Health
      Organization/United Nations Children's Fund (WHO/UNICEF) now include zinc
      treatment, 20 mg per day for 10 days. To determine if a dispersible zinc sulphate
      tablet formulation is associated with increased risk of vomiting or regurgitation
      following the initial, first treatment dose, a double-blind, placebo-controlled
      randomized clinical trial was carried out in the Dhaka hospital of ICDDR,B:
      Centre for Health and Population Research (n=800) and in an adjacent NGO
      outpatient clinic (n=800). Children were randomized to one of three groups: no
      treatment, placebo, or zinc sulphate tablet (20 mg). They were then observed for
      60 minutes, and all vomiting or regurgitation episodes were recorded. When
      compared with placebo, zinc treatment resulted in an attributable risk increase
      of 14% for vomiting and 5.2% for regurgitation. The median time to vomiting among
      those receiving zinc was 9.6 minutes and was limited to one episode in 91.2% of
      the cases. Overall, the proportion of 60-minute post-treatment vomiting
      attributable to zinc, placebo, and the illness episode was estimated to be 40%,
      26%, and 34% respectively. The dispersible zinc sulphate tablet formulation at a
      dose of 20 mg is associated with increased risks of vomiting and regurgitation.
      Both are transient side-effects.

PMID- 16599102
TI  - Intensive nutrition education with or without supplementary feeding improves the
      nutritional status of moderately-malnourished children in Bangladesh.
AB  - This prospective randomized trial was carried out to test the efficacy of a
      specific intervention for reducing the extent of their malnutrition and to change
      behaviour of mothers relating to child-feeding practices, care-giving, and health
      seeking practices under the Bangladesh Integrated Nutrition Project (BINP). The
      study was conducted in rural Bangladesh among 282 moderately-malnourished (weight
      for-age between 61% and 75% of median of the National Center for Health
      Statistics standard) children aged 6-24 months. Mothers of the first intervention
      group received intensive nutrition education (INE group) twice a week for three
      months. The second intervention group received the same nutrition education, and
      their children received additional supplementary feeding (INE+SF group). The
      comparison group received nutrition education from the community nutrition
      promoters twice a month according to the standard routine service of BINP. The
      children were observed for a further six months. After three months of
      interventions, a significantly higher proportion of children in the INE and
      INE+SF groups improved (37% and 47% respectively) from moderate to mild or normal
      nutrition compared to the comparison group (18%) (p < 0.001). At the end of six
      months of observation, the nutritional status of children in the intervention
      groups improved further from moderate to mild or normal nutrition compared to the
      comparison group (59% and 86% vs 30%, p < 0.0001). As the intensive nutrition
      education and supplementation given were highly effective, more children improved
      from moderate malnutrition to mild or normal nutritional status despite a higher
      incidence of morbidity. The frequency of child feeding and home-based
      complementary feeding improved significantly (p < 0.001) in both the intervention
      groups after three months of interventions and six months of observation. Body
      weight gain was positively associated with age, length-for-age, weight-for
      length, frequency of feeding of khichuri, egg, and potato (p < 0.05). Ability of
      mothers to identify malnutrition improved from 15% to 99% in the INE group and
      from 15% to 100% in the INE+SF group, but reduced from 24% to 21% in the
      comparison group. Use of separate feed pots, frequency of feeding, and cooking of
      additional complementary feeds improved significantly in the INE and INE+SF
      groups compared to the comparison group after three months of interventions and
      six months of observation. It can be concluded from the findings of the study
      that intensive nutrition education significantly improves the status of
      moderately-malnourished children with or without supplementary feeding.

PMID- 16599103
TI  - Corticosteroid-responsive enteropathy of infancy.
AB  - Nineteen American infants aged less than three months developed persistent
      diarrhoea, acidosis, hypoalbuminaemia, and malnutrition, without evidence of
      enteric pathogens. Symptoms began 11-59 days before admission to the University
      of North Carolina Children's Hospital, and infants were fed semielemental
      formula. Despite further treatment with amino acid-based formula by continuous
      nasogastric infusion, diarrhoea persisted. Endoscopic biopsies showed
      inflammation in the stomach, duodenum, and/or colon. A trial of intravenous
      corticosteroids was initiated in 14 infants. Corticosteroids were associated with
      rapid resolution of diarrhoea (duration after corticosteroids = 3.8 +/- 1.7 days
      [mean +/- SD]). In contrast, five infants with identical history were not treated
      with corticosteroids. In three infants, diarrhoea lasted for 92-147 days versus
      31 +/- 3 total days in the treated group. In the other two infants, diarrhoea
      worsened after discharge, but were treated later with corticosteroids, with rapid
      resolution. Corticosteroids were uneventfully weaned over a four-month period.
      The results suggest that a trial of corticosteroids in infants with unresponsive
      persistent diarrhoea of unknown origin is beneficial and deserves prospective
      evaluation.

PMID- 16599104
TI  - Prevalence of Shigella species and their antimicrobial resistance patterns in
      Eastern Nepal.
AB  - The study was conducted to determine the prevalence of Shigella species and their
      antimicrobial resistance patterns in eastern Nepal. Stool samples submitted to
      the diagnostic laboratory of B.P. Koirala Institute of Health Sciences, Nepal,
      during August 2000-July 2004, were cultured for Shigella species and were
      confirmed by biochemical and serological tests. Of 53 Shigella species isolated,
      Shigella dysenteriae type 1 was the most predominant isolate (73.7%), followed by
      S. flexneri (23%) and S. boydii (4%). The majority (79%) of Shigella species were
      isolated from children aged less than five years. An overall high resistance was
      observed for trimethoprim-sulphamethoxazole, ampicillin, nalidixic acid,
      mecillinam, and ciprofloxacin. There was a statistically significant (p < 0.001)
      increasing trend in the prevalence of ciprofloxacin resistance in S. dysenteriae
      type 1. The results suggest reconsideration of the empiric use of these
      antimicrobial agents for shigellosis. A further study is required to evaluate
      additional antimicrobial agents.

PMID- 16599105
TI  - Status of carotenoids, vitamin A, and vitamin E in the mother-infant dyad and
      anthropometric status of infants in Malawi.
AB  - This prospective study was carried out during February 2000-April 2003 to
      characterize the relationship between the status of carotenoids, vitamin E, and
      retinol and anthropometric status in apparently healthy infants and their mothers
      in Blantyre, Malawi. Anthropometric status of infants and concentrations of
      carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein,
      zeaxanthin, and lycopene), retinol, and alpha-tocopherol in plasma were measured
      in 173 infants at 12 months of age, and concentrations of carotenoids, retinol,
      and a-tocopherol in plasma were measured in their mothers two weeks postpartum.
      In multivariate analyses, concentrations of retinol, total carotenoids, non
      provitamin A carotenoids, and alpha-tocopherol in infants were associated with
      under-weight (p = 0.05). Concentrations of a-tocopherol were associated with
      wasting (p = 0.04). Concentrations in mothers and infants were all correlated
      (correlation coefficients from 0.230 to 0.502, p < 0.003). The findings suggest
      that poor status of carotenoids, retinol, and alpha-tocopherol in infants is
      associated with their poor anthropometric status, and status of carotenoids,
      retinol, and alpha-tocopherol in mothers and infants has a low-to-moderate
      association in the mother-infant dyad.

PMID- 16599106
TI  - Supplemental feeding with ready-to-use therapeutic food in Malawian children at
      risk of malnutrition.
AB  - The study was a controlled, comparative clinical effectiveness trial of two
      supplementary feeding regimens in children at risk of malnutrition from seven
      centres in rural Malawi. Being at risk of malnutrition was defined as weight-for
      height <85%, but >80% of the international standard. A stepped-wedge design with
      systematic allocation was used for assigning children to receive either ready-to
      use therapeutic food (RUTF) (n=331) or micronutrient-fortified corn/soy-blend
      (n=41) for up to eight weeks. The primary outcomes were recovery, defined as
      weight-for-height >90%, and the rate of weight gain. Children receiving RUTF were
      more likely to recover (58% vs 22%; difference 36%; 95% confidence interval [CI]
      20-52) and had greater rates of weight gain (3.1 g/kg.d vs 1.4 g/kg x d;
      difference 1.7; 95% CI 0.8-2.6) than children receiving corn/soy-blend. The
      results of this preliminary work suggest that supplementary feeding with RUTF
      promotes better growth in children at risk of malnutrition than the standard
      fortified cereal/legume-blended food.

PMID- 16599107
TI  - Prevalence and incidence of, and risk factors for, HIV-1 infection among factory
      workers in Ethiopia, 1997-2001.
AB  - The study was conducted to determine the prevalence, incidence, and risk factors
      for HIV infection among factory workers at two sites in Ethiopia. During February
      1997-December 2001, a structured questionnaire was used for obtaining information
      on sociodemographics, sexual behaviour, and reported sexually transmitted
      infections (STIs) from a cohort of 1679 individuals. Serum samples were screened
      for antibodies against HIV, Treponema pallidum haemaglutination (TPHA), and
      herpes simplex virus type 2 (HSV-2). The overall baseline prevalence of HIV was
      9.4%-8.5% among males and 12.4% among females. For both the sexes, the factors
      independently associated with an increased risk of HIV infection were widowhood
      and having had antibodies against TPHA and HSV-2. The risk factors specific for
      males were being orthodox Christian, having had a higher lifetime number of
      sexual partners, and genital discharge in the past five years. The risk factors
      for females, included low income, one or more rape(s) over lifetime, and casual
      sex in the last year. The overall incidence of HIV infection was 0.4 per 100
      person-years. The highest rate of incidence was observed among young women aged
      less than 30 years (1 per 100 person-years). The study confirmed that high-risk
      sexual behaviour and STIs play major roles in the spread of HIV infection in the
      Ethiopians of both the sexes, but the factors, such as rape and low economic
      status, make women more vulnerable than men.

PMID- 16599108
TI  - Seeking optimal means to address micronutrient deficiencies in food supplements:
      A case study from the Bangladesh Integrated Nutrition Project.
AB  - In seeking to improve the micronutrient contents of a food supplement used in a
      major community-based nutrition project in Bangladesh, operations research was
      conducted to compare the provision of needed micronutrients through additional
      food sources (fresh or dried fruits or vegetables), a micronutrient multi-mix,
      and a combination of the two. Micronutrient gaps (the difference between
      micronutrient requirements and actual micronutrient intake) were estimated for
      four groups of project beneficiaries, with target intakes defined as requirements
      for iron, calcium, zinc, vitamin A, vitamin C, riboflavin, niacin, and vitamin
      B12 recommended by the Food and Agriculture Organization/World Health
      Organization. Primary focus was placed on iron and vitamin A. Cost and bulk
      constraint analyses, based on cost of supplement, feasibility of delivery, and
      serving volume needed to achieve micronutrient targets, were used for comparing
      the supplement options. In terms of these analyses, the micronutrient multimix
      proved, by far, to be the most advantageous. Food options, however, are arguably
      desirable in that they provide dietary benefits additional to that of known
      micronutrients and may increase demand to boost production of domestic fruits and
      vegetables for the population as a whole. The study concludes that it is cost
      effective to use powdered micronutrient mixes for such specific purposes as
      enrichment of supplementary food and food fortification, but encourages
      production and consumption of micronutrient-rich foods through programme messages
      and activities.

PMID- 16599109
TI  - Effectiveness of depot-holders introduced in urban areas: evidence from a pilot
      in Bangladesh.
AB  - Depot-holders are women from the community who promote good health practice and
      use of clinics. They keep a stock of contraceptives and oral rehydration salts to
      supply other women and are paid some incentives. In 2003, the NGO Service
      Delivery Program (NSDP) introduced depot-holders in three types of urban area in
      Bangladesh as a pilot. This evaluation study was carried out to: (a) establish a
      baseline for measuring the impact of activities of depot-holders on a
      comprehensive range of indicators in the long-term, (b) make a preliminary
      assessment of the impact on the use of selected services of the essen-tial
      services package (ESP) and other indicators at the end of the pilot phase, and
      (c) assess the cost of introducing depot-holders and running their activities for
      a year. Data from the baseline and end of pilot household surveys, together with
      service statistics from the intervention and comparison areas, were used for
      assessing the changes in clinic use and commodity distribution. The study found
      evidence that the depot-holders transferred knowledge to women in the community,
      provided services, and referred women to clinics run by non-governmental
      organizations (NGOs). There was a large increase in the number of client contacts
      at the NGO clinics and in the quantity of oral contraceptive pills and oral re
      hydration salts distributed by the NGOs, mostly attributable to the activities of
      the depot-holders. The estimated cost per depot-holder per year was Tk 15,241
      (U.S. dollars 262). Overall, the performance of the depot-holders in the pilot
      phase suggests that they can be introduced in different types of urban area and
      can be effective in their dual role as providers and promoters of services.

PMID- 16599110
TI  - Acquisition of bed-nets, sleeping-habits, and control of malaria in the Gambia:
      sociocultural dimension.

PMID- 16599111
TI  - [Numerical simulations of spatial and temporal characteristics of airborne dust
      over Asia during springs of 2000 to 2002].
AB  - Spatial and temporal characteristics of airborne dust over Asia during springs of
      2000, 2001 and 2002 were simulated with a mineral dust entrainment and deposition
      model (DEAD) embedded in a global model of atmospheric transport and chemistry
      (MATCH) using the real-time meteorological data as forcing fields. The results
      show a good agreement of the pattern of model-simulated atmospheric dust
      concentration with the distribution of surface-observed spring dust storm
      frequency and a significant correlation between the simulated dust aerosol
      optical depth (DAOD) and satellite-observed aerosol index (AI). These results
      validate applicability of the integrated model in simulating dust entrainment,
      transportation and deposition and describing spatial and temporal characteristics
      of dust loading over the Asian continent. In addition, an attempt was made to
      explore possible paths of dust transportation by use of correlation analyses
      between the simulated dust emission flux (DEF) and DAOD.

PMID- 16599112
TI  - [Ozone and carbon monoxide concentration distribution on Taishan Mountain].
AB  - The concentrations of ozone (O3) and carbon monoxide (CO) on the top of Taishan
      Mountain were monitored, and the variations and correlation were studied. The
      results show that the frequency of O3 hourly concentrations more than the first
      degree of National Ambient Air Quality Standard(GB-3095-1996, NAAQS) was 15.81%,
      and the frequency of CO concentrations more than the first-degree of NAAQS was
      zero. The variation of O3 concentrations appears in a narrow scope, which
      indicates that there is scarcely influenced by the pollution of industry around.
      The diurnal variation of the concentrations of O3 and that of CO both present two
      peaks with the peaks of O3 in the behind of CO, which indicates that the
      concentration variations of O3 and its precursor CO are primarily controlled by
      local photochemical reaction process. The daily concentrations of O3 correlated
      well with CO.

PMID- 16599113
TI  - [On-line method for measurement of the carbon isotope ratio of atmospheric
      methane and its application to atmosphere of Yakela condensed gas field].
AB  - An on-line method for measurement of the 13C/12C ratio of methane by a gas
      chromatography/high-temperature conversion/ isotope ratio mass spectrometry
      (GC/C/MS) technique was developed. This method is less laborious, more rapid (45
      min), of high precision (+/- 0.4 x 10(-3)) and by using a small amount of sample
      (about 200 mL of atmosphere). Its application to isotopic characterization, and
      hence methane source identification, was demonstrated by examination of
      atmosphere sample collected in Yakela condensed gas field, China. The average
      13C/12C ratio of atmospheric methane in Yakela field was -45.0 x 10(-3) heavier
      by 1.2 x 10(-3) -2.0 x 10(-3) than the global average. This is caused by seepage
      and diffusing of methane from Yakela condensed gas reservoir. The concentrations
      of atmospheric methane in daytimes are found to be lower than those in
      nighttimes, and the corresponding 13C/12C ratios in daytimes are lighter compared
      to those in nighttimes, a phenomena probably caused by the fact that a small part
      of methane from Yakela condensate reservoir is consumed in soil's surface under
      sunlight.

PMID- 16599114
TI  - [Pathways of mercury emissions to atmosphere from closed municipal landfills].
AB  - Using the automated mercury vapor analyzer and dynamic flux chamber (DFC) method,
      the pathways of mercury emissions to atmosphere were measured at a closed
      landfill in Wuhan, China. The results show that the mainly pathway is by the
      surface cover, and emissions from vent pipes is negligible. Average Hg fluxes
      during the observation period was (192.5 +/- 245.3) ng x (m2 x h)(-1), which was
      1 - 2 orders of magnitude greater than that from background zone. Hg flux
      exhibited a clearly diurnal pattern, reaching the maximum near midday and the
      lowest during night. Solar radiation was the environmental factor that has
      highest relationship with Hg flux, with coefficient of 0.77, this indicated that
      photo-reduction of Hg(II) being a prominent process in the production of volatile
      elemental mercury (Hg(0)). Mercury concentrations in landfill gas (LFG) at
      different vent pipes averaged from 7.0 - 68.9 ng x m(-3), which was much lower
      than that of operational landfills, and the flow rate of landfill gas was very
      slow.

PMID- 16599115
TI  - [Markov Chain Monte Carlo scheme for parameter uncertainty analysis in water
      quality model].
AB  - Parameter identification plays an important role in environmental model
      application. Markov Chain Monte Carlo method was introduced to estimate parameter
      uncertainty, since usual Bayes discrete methods were not applicable to produce
      posterior distribution of complicated environmental model due to the limit of
      computation. In order to study the performance and efficiency of MCMC, two case
      studies were used. Results indicate that, either sampling performance or sampling
      efficiency, MCMC method both has its special advantages in producing posterior
      distribution. Moreover, results of Gelman convergence diagnostics indicate that
      sampling sequence can converge to a stationary distribution. A key finding was
      that the MCMC scheme presented herein provided a powerful means of parameter
      identification and uncertainty analysis.

PMID- 16599116
TI  - [Zoning planning in non-point source pollution control in Hanyang district].
AB  - It is most important for managing urban non-point source (NPS) pollution,
      actualizing the urban sustainable development as well, that zoning planning of
      urban NPS pollution control is studied. A case study on principles and methods of
      zoning planning in urban NPS pollution is carried out. Principles of urban
      sustainable development, priority of urban NPS pollution sensitivity, similarity
      of urban NPS control direction and region conjugate are put forward. Besides, it
      is for the first time that a more quantitive method is presented, in the case of
      Hanyang district, Wuhan city, which is based on L-THIA model and spatial analysis
      technique in GIS. Assessment of NPS pollution status quo, as well as analysis of
      NPS sensitivity, is the kernel component of the quantitive method. Hanyang might
      be divided into four NPS pollution control zones. It is helpful for decision
      making of regional NPS pollution control.

PMID- 16599117
TI  - [Ecological mechanisms of the effects of vegetation restoration on the controls
      of non-point source pollution on barren tableland in Dianchi Watershed of China].
AB  - Surface runoff, soil erosion and the leaching of the different forms of nitrogen
      and phosphorus were observed and the hygroscopic volume of branch and leaves of
      all plant species and soil penetration were determined to understand the
      ecological mechanisms of the effects of vegetation restoration on the controls of
      non-point source pollution on barren tableland in Dianchi Watershed of China.
      Results indicated that there were significantly relationships between surface
      runoff volume and the output of non-point pollution matters. The different
      manmade vegetation systems, consisted respectively of A. nepalensis, A. mearnsii,
      R. pseudoacacia and V. zizanioides clump, had shown the different potentials to
      control the leaching of TN, TP, soluble TP, soluble TN. Strong hygroscopic
      functions of leaves and branch was able to promote the interception of rainfalls
      and give rise to the less of surface runoff. The leaves, that were small, with
      low water content, no leathery and have rough face and epidermal wools, were able
      to got the highly ratio of the hygroscopic volume to above ground fresh standing
      crops and strengthened the interception of forest canopy. Preparing soil, growth
      of root system of plant and the natural recovery of vegetation at the gap of
      trees enhanced surface runoff penetration, as lightened the surface runoff
      leaching the different forms of nitrogen, phosphorus of soil on the stands. The
      leaching of different forms of nitrogen and phosphorus went down with the
      controls of surface runoff in different stands as well.

PMID- 16599118
TI  - [Improvement of PVC bio-carrier surface property by remote plasma].
AB  - The effects of various remote plasma, such as Ar, He, O2 and N2 on PVC bio
      carrier surface modification were studied. The surface properties were
      characterized by the contact angle measurement and X-ray photoelectron
      spectroscopy (XPS). The role of all kinds of active species such as electrons,
      ions and free radicals involved in plasma surface modification were evaluated.
      Results show that the remote plasma treatments modify the PVC surface in both
      wettability and composition, the (O + N)/C of PVC surface increases from 7% to
      22%, and the water contact angle decreases from 97 degrees to 15 degrees. The
      optimal results was achieved when plasma treatment parameters were set, that is
      treatment time 3 min, Ar flux at 20 cm3/s, power at 60W, sample position of 40
      cm. The results show that the modified PVC Bio-carrier adhesion rate and capacity
      on the modified surface are greatly increased.

PMID- 16599119
TI  - [Study on oxidant strengthening photocatalytic degradation of DMF over TiO2 fiber
      catalyst].
AB  - Oxidant strengthening the degradation of DMF aqueous solution was investigated
      when TiO2 fiber is used as the photocatalyst. When the UV light was absent, ozone
      per se could not make DMF degrade, which proves that DMF is a stable substance.
      But ozone could increase obviously photocatalytic degradation rate of DMF in
      O3/TiO2 (F). Under the same reaction condition, photocatalytic degradation rate
      and speed of DMF in O3/TiO2 (F) was almost 1.5 times and 2 times higher than that
      in air/ TiO2 (F) and H2O2/TiO2 (F) respectively. COD analysis showed DMF was
      almost mineralized completely when the reaction was carried out for 120 min.
      Through Hinsberg test secondary amine was proved as one of intermediates in the
      process of DMF photocatalytic degradation. Rise of pH value of reaction solution
      also showed that amine was produced in the photocatalytic reaction process.
      Degradation speed of DMA in O3/TiO2 (F) was higher than that in air/TiO2 (F). The
      increasing degradation rate and speed of DMF was mainly caused by fast
      degradation of secondary amine in the process of DMF photocatalytic degradation
      in O3/TiO2 (F).

PMID- 16599120
TI  - [Catalytic oxidation of dimethyl phthalate in aqueous solution by aluminum
      oxide].
AB  - With dimethyl phthalate as the model pollutant and alumina as catalyst, the
      degradation of TOC system was systemically investigated. Results show that Al2O3
      can significantly increase the effect of ozonation, and TOC removal rate in 120
      minutes can reach 55.1% while only 23.9% with alone ozone. Al2O3 activeness is
      upmost under the follow conditions: calcination temperature, 600 degrees C;
      particle diameter, 0.5 - 1 mm; catalyst dosage, 20 g/L; gas flow rate, 200
      mL/min, react temperature, 15 degrees C. The contrastive experiments of alone
      ozone, catalyst adsorption after ozonation and catalytic ozonation confirmed that
      catalytic reaction is the most important process to TOC removal in system with
      alumina as catalyst.

PMID- 16599121
TI  - [Characteristics of aerobic granular sludge membrane bioreactor for wastewater
      treatment].
AB  - Characteristics of aerobic granular sludge membrane bioreactor (MBR) and the
      membrane fouling were studied with synthetic wastewater. Experimental results
      showed that COD removal rate could be reached over 96% under the conditions of
      HRT = 6h, DO 4 - 6 mg x L(-1) and the volumetric load of COD = 7.24 kg x (m3 x
      d)(-1). When the volumetric load of NH3-N was 0.17 kg x (m3 x d)(-1), the removal
      rate of NH3-N was about 60%. The variations of the COD/N ratio could not affect
      the removal of COD and NH3-N. During the stable operation process, MLSS of the
      reactor was as high as 14 - 16 mg x L(-1), which could conduce simultaneous
      nitrification-denitrification, as the anoxic and anaerobic microorganisms might
      be existed in the core of granular sludge. In addition, the membrane flux of MBR
      of two different configurations of sludge, granular sludge and floccular sludge,
      was compared. The flux reduction of granular sludge MBR was much lower than that
      of floccular sludge MBR. Moreover, the membrane permeability of the granular
      sludge MBR could be regained simply by backwashing with aeration or washing the
      membrane with water.

PMID- 16599122
TI  - [Continuous bio-hydrogen production by mesophilic and thermophilic cultures].
AB  - Anaerobic biological hydrogen productions were achieved successfully in two lab
      scale anaerobic hydrogen production reactors under mesophilic (37 degrees C) and
      thermophilic (55 degrees C) conditions, respectively. The mesophilic reactor, a
      CSTR, was operated over 4 months by seeding with river sediments and feeding with
      glucose solution, in which the highest hydrogen production rate was 8.6 L/(L x d)
      and the substrate hydrogen production molar ratio (H2/glucose) was 1.98. After
      seeded with anaerobic methanogenic granules, a UASB reactor was thermophilically
      operated by feeding with sucrose solution and during its steady operation period,
      the hydrogen production rate was 6.8 L/(L x d) and the substrate hydrogen
      production molar ratio (H2/sucrose) was 3.6. Within the produced gas, the H2
      percentages were about 43% and others were CO2, no methane could be detected.
      Thermophilic hydrogen-producing granules were successfully cultivated in the UASB
      reactor, which were grey-white in color, the diameters were about 0.8 - 1.2 mm,
      and typical settling velocities were about 30 - 40 m/h. Through SEM a great
      number of bacilli could be found on the surface of the granules which made the
      surface rough. Total DNA of these two hydrogen production sludges were extracted
      and purified, and the PCR and DGGE process were conducted, the results indicate
      that most of the eubacteria in two sludges are the same, but the dominant species
      are obviously different with each other.

PMID- 16599123
TI  - [Nitrification and denitrification in BACF for treating high ammonia source
      water].
AB  - A high ammonia micropolluted source water advanced treatment for ammonia removal
      by biological activated carbon filter was tested. The removal rate of ammonia was
      high than 95% when influent concentration was under 1.0 mg/L. The removal rate
      decreased with the influent concentration increased when the ammonia
      concentration was in range of 1.5 - 4.9 mg/L and the influent DO was under 10
      mg/L, and the minimum removal rate was about 30%. The key factor of restrict
      nitrification in BACF was the influent DO. When the influent ammonia
      concentration was high, the DO in water was depleted quickly by nitrify and
      hetetrophic bacteria in 0.4 m deep of filter and the filter layer was divided to
      aerobic zone and anoxic zone. The denitrification was occurred in the anoxic
      zone, and because of very low concentration of electron donor led to accumulation
      of the denitrification intermediates such as NO2-. Aerobic bacteria was existed
      in the anoxic zone.

PMID- 16599124
TI  - [Simultaneous control of microorganism, disinfection by-products and bio
      stability by sequential chlorination disinfection].
AB  - A new safe chlorination disinfection process, the sequential disinfection process
      with short-term free chlorine plus chloramines was investigated its efficiency on
      control of indices of microorganism, disinfection by-products and bio-stability.
      This disinfection process may take the advantage of free chlorine's quick
      inactivation of microorganism and chloramines' low DBP yield and long-term
      residual. Thus, both control of microorganisms and DBPs can be achieved
      effectively and economically. The pilot test results show that safe chlorination
      disinfection process has a little better efficiency on total bacteria count, HPC
      and total coliform count than free chlorination disinfection, which indicate that
      free chlorine and chloramines might have the synergetic disinfection effect for
      their different attacking targets. It also had the same inactivation efficiency
      on polio virus and coliphage f2 as free chlorination in 120 minutes contact time.
      Sequential chlorination disinfection process could reduce 35.8% - 77.0% yield of
      trihalomethane and 36.6% - 54.8% yield of haloacetic acids. The poorer quality
      the water had, the more advantage the safe-chlorination disinfection had than
      free chlorination disinfection one. Moreover, sequential chlorination had better
      efficiency on bio-stability control than free chlorination.

PMID- 16599125
TI  - [Removal of coliphages by wastewater treatment processes].
AB  - The concentrations of somatic coliphages (SC) and F-specific RNA bacteriophages
      in effluent of three wastewater treatment plants in Beijing city were detected.
      Somatic coliphages and F-RNA bacteriophages in source wastewater were 6.25 x
      10(3) - 1.34 x 10(4) PFU x mL(-1) and 2.4 x 10 - 2.4 x 10(3) PFU x mL(-1)
      respectively, and the corresponding average removal rates were 72.45% - 99.89 %
      and 57.84% - 93.06% by the wastewater processes, and which were lower than that
      of faecal coliforms. Biological aerated stage appeared to be the most efficient
      step in reducing the numbers of phages in wastewater, but not obviously in sand
      filter. The result of predicted concentrations of enteroviruses according to
      concentrations of F-RNA bacteriophages in water show that there are 0.65 - 15.8
      PFU x L(-1) of the enteroviruses in final effluent.

PMID- 16599126
TI  - [Roles of EDTA on phytoremediation of combined contamination in dredged sewage
      river sediment].
AB  - Pot experiments were conducted to study the roles of EDTA in phytoremediation of
      heavy metal-organic contaminated dredged sewage river sediment by Lolium
      multiflorum L. 3 mmol x kg(-1) EDTA was added to sediment through three manners
      (once, twice and three times, respectively). The results showed that: with adding
      EDTA to the sediment. (1) The accumulation amount of heavy metals to Lolium
      multiflorum L. increased, especially by added EDTA three times. Compared with the
      control, the accumulation of Pb, Zn, Cu, Ni, Cd in shoots increased 2.74, 1.99,
      1.59, 1.55 and 7.78 times by added EDTA three times. The net increment was 32.33
      mg x kg(-1), 1 393.56 mg x kg(-1), 64.42 mg x kg(-1), 36.57 mg x kg(-1) and 10.33
      mg x kg(-1), respectively. Furthermore, the concentration of chlorophyll
      decreased by 42% with 3 times EDTA addition, while the concentration of
      chlorophyll has no significant change with once EDTA addition. (2) pH hasn't much
      change, while NH4OAc and DTPA extractable heavy metal amount from sediment
      increased significantly. (3) The bulk percentage of big particle sediment
      increased. By added EDTA three times to sediment, the average particle size of
      sediment increased, while specific surface area and crystal lattice intensity
      decreased, which were contributed to the desorption of heavy metal from sediment
      particle. (4) Compared with the control, the amount of microorganism in sediment
      was increased 1.33 times and 1.47 times with adding EDTA twice and three times.
      The urease activity decreased, while the catalase activity hasn't much change.
      (5) TOC content was increased.

PMID- 16599127
TI  - [Simultaneous sorption of aqueous phenanthrene and phosphate onto bentonites
      modified with AlCl3 and CTMAB].
AB  - Inorganic-organic bentonites (Al-CTMAB-Bent) were synthesized by modifying
      bentonites with AlCl3 and cetyltrimethyl ammonium bromide (CTMAB). Simultaneous
      sorption of aqueous phenanthrene and phosphate onto Al-CTMAB-Bent were examined.
      Removal rates of phenanthrene and phosphate from water are 96.3% and 90.2%,
      respectively, at their respective initial concentrations of 1 mg/L and 5 mg/L
      when the added amount of Al-CTMAB-Bent was 1.25 g/L. The residual turbidity of Al
      CTMAB-Bent suspension decreased 81.4% comparing to that of organobentonite
      suspension after 1 hour settlement. Thus inorganic-organic bentonite can be used
      to treat wastewater containing both organic pollutants and phosphate.

PMID- 16599128
TI  - [Factors affecting biological removal of iron and manganese in groundwater].
AB  - Factors affecting biological process for removing iron and manganese in
      groundwater were analyzed. When DO and pH in groundwater after aeration were 7.0 
      7.5 mg/L and 6.8 - 7.0 respectively, not only can the activation of Mn2+
      oxidizing bacteria be maintained, but also the demand of iron and manganese
      removal can be satisfied. A novel inoculating approach of grafting mature filter
      material into filter bed, which is easier to handle than selective culture media,
      was employed in this research. However, this approach was only suitable to the
      filter material of high-quality manganese sand with strong Mn2+ adsorption
      capacity. For the filter material of quartz sand with weak adsorption capacity,
      only culturing and domesticating Mn2+ oxidizing bacteria by selective culture
      media can be adopted as inoculation in filter bed. The optimal backwashing rate
      of biological filter bed filled with manganese sand and quartz sand should be
      kept at a relatively low level of 6 - 9 L/(m2 x s) and 7 -11 L/( m2 x s),
      respectively. Then the stability of microbial phase in filter bed was not
      disturbed, and iron and manganese removal efficiency recovered in less than 5h.
      Moreover, by using filter material with uniform particle size of 1.0 - 1.2 mm in
      filter bed, the filtration cycle reached as long as 35 - 38h.

PMID- 16599129
TI  - [Effects of nitrogen source and aeration mode on algae growth in freshwater].
AB  - Aquarium microcosms were used to study the effects of nitrogen source and
      aeration mode on the growth and species changes of algae in freshwater. Nitrate
      nitrogen(NO3(-) -N) and ammonia nitrogen(NH4(+) -N) were used as nitrogen
      sources. For each nitrogen source, four modes of aeration were selected,
      including control, continuous aeration, aeration during the day, and aeration at
      night. In the early stage of the experiment, algae in the NH4(+) -N treatment
      experiment grew well. In the later stage, algae in the NO3(-) -N treatment
      experiment grew better. For different aeration modes, continuous aeration show
      varied effects on algae growth in the two nitrogen source treatments. Day-only
      aeration had little effect on algae growth. Night-only aeration inhibited algae
      growth considerably. In NH(+) -N treatments, cyanophyta became dominant species
      easily. In contrast, chlorophyta dominated in NO3(-) -N treatments.

PMID- 16599130
TI  - [Distribution of phosphine and microorganisms in partial sediments of Lake
      Taihu].
AB  - Phosphine in Lake Taihu sediment cores were monitored by a GC/NPD method, coupled
      with cryo-trapping enrichment technology. Results show that phosphine is
      universally detected in sediment cores, its concentration ranges from 0.15 ng/kg
      to 36.1 ng/kg. The concentration of phosphine varies with different sampling
      sites and depths. Representative microorganisms (aerobic bacteria, anaerobic
      bacteria, actinomycete, inorganic phosphobacteria and organic phosphobacteria) in
      surface sediments were also identified. The amount and distribution of
      microorganisms positively correlate with different contamination and salty levels
      of the samples. A markedly positive linear correlation between the concentration
      of phosphine and the numbers of inorganic phosphobacteria could be observed (R2 =
      0.817, n = 6). There is not a correlation between phosphine level and organic
      phosphobacteria quantities.

PMID- 16599131
TI  - [Distribution of polychlorinated biphenyls (PCBs) in suspended particulate
      matters from the Yangtze estuarine and coastal areas].
AB  - Polychlorinated biphenyls (PCBs) in suspended particulate matters (SPMs) from the
      Yangtze estuary and coastal areas were determined with GC-ECD. The results show
      that concentrations of PCBs range from 2.5 - 51.5 ng/g, with an average of 13.2
      ng/g. PCBs concentrations are higher in SPMs than in surface sediments at most of
      sampling stations. It was also found that the distribution of PCBs had no
      significant relationship with grain size and organic matter. In addition, the
      congeners of PCBs were characterized by less chlorinated compounds, with 2 - 5CB
      accounting for 74.9% - 100% except at Donghai site, and 2CB was dominant among
      the congeners of PCBs in all samples, which maybe be related to the history of
      production and use for PCBs in China. But it was different from the surface
      sediments that dominated by 3CB, which showed that there was new inputs recently.
      Compared with the concentration levels of PCBs at other estuarine and coastal
      areas, it was shown that there existed a moderate level of contamination in the
      study area.

PMID- 16599132
TI  - [Effect of particles on the photodegradation of PAHs in natural waters of the
      Yellow River].
AB  - Photodegradation of chrysene, benzo(a)pyrene and benzo(ghi)perylene in natural
      water of the Yellow River was studied using simulation sunlight. The effects of
      particulates on the photodegradation were explored. Several results arose from
      this study: (1) The photodegradation of PAHs can be fitted with first-order
      kinetics when no particulates exist in water system, and the first-order constant
      increase with the decrease of initial concentration of PAHs. The photodegradation
      rates of the three PAHs are related to their molecule absorption spectrum. (2)
      The presence of loess exerts two kinds of effects on the photodegradation of
      PAHs, which include the inner filter effects and the photosensitizing effects of
      humic substance in Loess. These two opposite effects lead to the difference of
      net effects among different contents of loess. When the loess contents are 0.1
      g/L and 5.0 g/L, the presence of loess stimulates the photodegradation of
      chrysene, benzo(a)pyrene. When the loess content is 5.0 g/L, the presence of
      loess stimulates the photodegradation of benzo(ghi)perylene. In addition, the
      photodegradation of PAHs can be fitted with the second-order kinetics when there
      is loess in the water system. (3) The dissolvable humic substances in loess can
      accelerate the photodegradation of PAHs while the indissoluble part cannot. (4)
      Since the dissolvable humic substances in the suspended solids of the river have
      been dissolved in water, the addition of suspended solids to the water system can
      only cause the decrease of photodegradation rate of PAHs due to its inner filter
      effects, and the photodegradation rate decreases with the suspended solid content
      as a power exponent function.

PMID- 16599133
TI  - [Dynamic fugacity model for describing the fate of persistent organic pollutants
      in the river].
AB  - Dynamic model depending on temperature with fugacity approach is formulated which
      describes the fate of Persistent Organic Pollutants (POPs) in a river. The
      fugacity capacity, the degradation rate and transfer coefficients of pollutants
      are depending on temperature in the model. The model is illustrated by
      calculating the fate of gamma-HCH in Liao River. The results show that from 273K
      to 298K, the fugacity capacities in air, water and sediment of gamma-HCH are
      respectively reduced in 8.4%, 89.7% and 89.7%. However, in the same range of
      temperature, the degradation rate coefficients in air, water and sediment, and
      volatilization and diffusion rate coefficients of gamma-HCH are increased in
      0.69, 22.0, 4.5, 7.9 and 1.6 times, respectively. The calculated value agree well
      with the field observed value in the order of magnitude, which shows that the
      model is appropriate for simulating the fate of POPs in a long time.

PMID- 16599134
TI  - [Contents and distribution characteristics of heavy metals in water and sediment
      of intertidalite].
AB  - ICP-MS analytical technology was used to analyze the concentration of 13 heavy
      metals in surface water, pore water in sediment, suspended particulate matter,
      and sediment of intertidalite of Tianjin. Results show that both total amount and
      single concentration of heavy metals vary greatly in different media, the biggest
      and smallest values differ by 4 or 7 magnitudes. While the variation coefficients
      of the contents of total metals or single metal in the same medium are less than
      0.3 and 0.5 respectively except for the pore water. The average concentration of
      total dissolved heavy metals is 41.2 microg x L(-1), while total contents of
      heavy metals in original water, pore water, sediment and suspended particles are
      62.7 microg x L(-1), 112.7 microg x L(-1), 262.3 mg x L(-1) and 345.0 mg x L(-1)
      respectively, they are similar to inland natural river but higher then those of
      ocean. The composition of heavy metals in different media varied greatly, metals
      prone to dissolve such as Mo account for more than 20% in water, but metals
      uneasy to dissolve mainly exist in sediment and suspended particles and absorbed
      by particles. Typical heavy metals, such as Zn, Cu, Pb and Cr, account for 40% -
      50% in water and 50% - 80% in other media. The similarity in distribution mode of
      heavy metals in intertidalite and terrestrial soil suggest that they are
      originated from terrestrial soil that is contiguity to the sea. Notable
      correlativity can be seen between concentrations of all heavy metals except for
      Mo in sediment, which can explain the similarity of their environmental behavior,
      but only wake correlation between the content of organic carbon and
      concentrations of heavy metals in suspended particulates and sediment.

PMID- 16599136
TI  - [Application of principal component analysis (PCA) for the estimation of source
      of heavy metal contamination in marine sediments].
AB  - Concentrations of heavy metals and organic matter in the bottom sediments of
      Jiaozhou Bay were determined and the average enrichment factors (AEFs) were used
      simultaneously to evaluate the extent of metal enrichment-contamination. Results
      show that heavy metal contamination in this bay could be divided into three
      groups: negligible to low contamination (AEFs < 2), which is the case of Zn (AEF
      = 1.11), Pb (AEF = 1.15), Cr (AEF = 1.52), Mn (AEF = 0.80) and Fe (AEF = 0.45);
      moderate contamination (AEFs = 2 - 3), which is the case of Cu (AEF = 2.79) and
      Cd (AEF = 2.52); certain to severe contamination (AEFs > 3), As (AEF = 3.03) and
      Hg (AEF = 8.08) being included in this group. Principal component analysis (PCA)
      was applied to estimate the sources of heavy metal contamination. Results that
      the first three components accounted for 52.61%, 17.37% and 15.60% of the total
      variance respectively exhibited that industrial wastewater, degradation of
      organic matter and erosion of rocks were the main sources of heavy metal
      contamination. The Q-analysis of PCA indicated that 14 stations could be divided
      into five groups. This result not only reflected the pollution characteristic of
      surface sediments, but also provided fundamental evidences for the putative
      analysis that industrial discharge is the main source of heavy metal
      contamination in Jiaozhou Bay.

PMID- 16599135
TI  - [Variation of particulate heavy metals in coastal water over the course of tidal
      cycle in estuary].
AB  - Variation characteristics and its mechanism of particulate heavy metals in
      coastal water over the course of tidal cycle on the eastern coast of Chongming
      Island in Yangtze Estuary were studied. Concentrations of Cu, Pb, Fe, Mn, Zn, Cr
      and Al in suspended particles in bottom water were respectively 184%, 99%, 56%,
      62%, 147%, 50% and 45% higher than those in surface sediments influenced by
      particle size. The concentrations of the reducible Cu, Pb, Fe, Mn, Zn and Al in
      suspended particles of bottom water were also two to three times of those in
      surface sediments, but percentages of the reducible fraction of the above
      mentioned elements in total metal concentrations in suspended particles were
      similar to those in surface sediments. High concentrations of particulate heavy
      metals occurred at the beginning of the food-tide, around the slack water and
      latter of the ebb tide over the course of five tidal cycles, which was mainly
      caused by the hydrodynamic conditions. When current velocity increased, the
      particulate heavy metals resuspended from bottom sediments diluted the perpetual
      suspended particles in water to a large extent. Environmental factors such as
      salt, dissolved oxygen and pH in water have little influence on the variations of
      particulate heavy metals over the course of tidal cycle.

PMID- 16599137
TI  - [Effect of chronic exposure by mercury contaminated rice on neurotransmitter
      level changes in rat brain].
AB  - In order to survey the potential health risk of environmental exposure by
      mercury, Sprague-Dawley rats were reared by mercury contaminated rice from
      mercury mining area. The changes of neurotransmitter acetylcholine (ACh) and
      acetylcholinesterase (AChE) in rat brain were examined at different times. The
      results show that the mercury-contaminated rice significantly increase the
      content of ACh in rat brain after exposure for 7 days. ACh maintained at a high
      level even after exposure for 30 days, but decreased significantly after exposure
      for 90 days. The changes of AChE represented an inverse trend compared with that
      of ACh. The coexisting selenium in rice exhibited antagonistic effects on both
      mercury accumulation and toxicity. The findings suggested that neurotoxic effects
      of environmental mercury contamination had been significantly represented after
      chronically dietary exposure. Further studies are needed to examine the
      relationship between the neurotransmitter level changes and the Alzheimer's
      Disease (AD).

PMID- 16599138
TI  - [Conjugation and immunogenic evaluation of complete immunogen for the small
      molecular environmental pollutants 2,4-D].
AB  - Conjugation of complete immunogen for 2,4-dichlorophenoxyacetic acid (2,4-D) was
      studied. 2,4-D was cross-linked to bovine serum albumin (BSA, carrier) by 1-ethyl
      3-(3-dimethyl- aminopropyl) carbodiimide hydrochloride (EDC). The conjugation
      reaction was found to be more effective at 4 degrees C and incubated for 18 hour.
      2,4-D was dissolved in 0.05 mol/L phosphate buffer between 10.0 - 12.0 mg/mL
      concentration, pH was adjusted to be 5.4 - 6.1. When the weight of added EDC was
      below 12 mg, the more EDC was added the higher substitution degree complete
      immunogen was synthesized. Complete immunogen of various substitution degree (2,4
      D: protein) were applied to immunize balb/c mice. The conjugates of 2,4-D and
      poly-L-lysine was applied as coating antigen. It was experimentally found that
      complete immunogen of substitution degree 12 and 18 are more immunogenic than
      that of substitution degree 6 and 25. None-specific adsorption between antiserum
      that was produced by complete immunogen of substitution degree 18 and coating
      antigen was very weak, and the antiserum contained more 2,4-D specific antibody.
      It could be used as the immunogen for the preparation monoclonal antibody.

PMID- 16599139
TI  - [Study on biodegradation of polyacrylamide].
AB  - Phanerochaete chrysosporium was introduced into biodegradation of
      polyacrylamide(PAM), and effects of glucose amount, pH, N concentration, Mn2+
      concentration and biodegradation time on biodegradation of PAM were studied.
      Results show that Phanerochaete chrysosporium has special abilities of enzyme
      catalysis biodegradation of PAM. And the removal rate of PAM is 50%. Nitrogen
      limitation (NH4+ = 0.2 g/L) and Mn2+ concentration (Mn2+ = 0.017 5 g/L) are
      optima of producing PAM biodegradation enzyme.

PMID- 16599140
TI  - [Effect of surfactants on biodegradation of PAHs by white-rot fungi].
AB  - The impacts of surfactants (Tween80, Trition X-100, LAS and SDS) on PAHs
      degradation by white-rot fungi in aqueous system and soil-water system were
      studied. Results show that the type and concentration of surfactants, PAHs
      statues, pH value of the systems and temperature have impacts on the degradation
      of PAHs. In aqueous system, all the four surfactants restrained the degradation
      of PAHs. In soil-water system, Trition X-100 and SDS restrained the degradation
      of PAHs, while the impacts of Tween80 and LAS on PAHs degradation were influenced
      by the concentration of the surfactants. Low concentration Tween80 and LAS didn't
      promote the degradation of PAHs, and even played minor effects of restrain. But
      the degradation of PAHs could be enhanced with the increasing of the
      concentrations of Tween80 and LAS to certain levels. However, Tween80 and LAS
      with significant higher concentrations didn't show higher abilities on the
      promotion of PAHs degradation.

PMID- 16599141
TI  - [Field-scale study on performance comparison of bio-augmentation and compost
      treatment of oily sludge].
AB  - In order to explore better treatment process of oily sludge, the field scale
      experiments were conducted using the sludge containing 12.68% oil. The
      performance of microbe preparation bio-augmentation (MPB) and compost treatment
      with manure (CTM) was compared. For the first experiment, 10 L solution
      containing 150 g microbe preparations and the nutrition were sprayed onto the
      MPBC cell. The initial oil content of final mixture amounted to 12.12%. The
      initial oil content of CTM after final mixture approximated to 10.14%. During the
      experimental period, same quantities of the microbe preparation and nutrient
      solution were sprayed on MPB at the 15th and 30th day separately. At the same
      days, the 10 kg manure was added to CTM cell. The degradation effect of MPB was
      more obvious, oil content dropped to 6.42% with a 47% removal rate of oil. The
      oil content in control decreased slightly to 10.15% after 56 days, while in CTM
      it fell down to 6.98% with a total removal rate of 31%. The pH in control
      fluctuated slightly between 8.28 to 7.93 while that in MPB, from 7.33 to 8.08,
      which might due to the addition of microbe preparation. The microbial count was
      analyzed weekly, which represented the adaptation ability of microbe in sludge.
      Temperature of compost increased rapidly up to 54 degrees C in the presence of
      manure. The differences of two kinds of methods were identified by GC-MS and the
      hydrocarbons with less 21 carbons were degraded easily.

PMID- 16599142
TI  - [Long-term sorption /desorption behavior of pyrene in soils].
AB  - Long-term sorption/desorption behavior of pyrene in six types of soils are
      investigated. The results show that long-term sorption and desorption entail two
      phases, including initially rapid process followed by a slow sorption/desorption.
      When soil organic matter (SOM) content was below 1%, the constant of sorption Kd
      of dissimilar soils increased with SOM content under different equilibrium time.
      While clay content played an important role in sorption capacity of the soils as
      SOM content was below 1%. In long-term sorption experiment, the Kd values of the
      six soils increased from 35.1% to 557.9%, respectively, with the sorption
      equilibrium time increased from 2 d to 180 d. Clay influenced significantly on
      Kd, while the effect of SOM was different, which suggested that the effect of
      sorption time on Kd of some soils could not be ignored. In long-term desorption
      experiment, the slow desorption percentages of pyrene from the six soils were in
      the range of 12.05% - 41.00%, with the tendency that the attribution of slow
      desorption fraction to desorption process increased with SOM. Ignoring the
      influence of aging on the sorption/desorption, it indicates that the attribution
      of SOM to the capacity of irreversible sorption compartment is distinctly higher
      than that of clay, which is consistent to the attribution of SOM to slow
      desorption process.

PMID- 16599143
TI  - [Effect of temperature control on vegetable waste and flower straw co
      composting].
AB  - The effect of temperature control on vegetable waste and flower straw co
      composting was investigated in pilot scale. The mixture of shredded vegetable
      waste and flower straw was composting in 2 m3 static aerobic bed on the controls
      of three different temperature level (55 degrees C, 60 degrees C, 65 degrees C).
      Of these trials, temperature, organic matter, moisture content were measured in
      order to research effect of temperature control on wastes reduction,
      biodegradation and moisture removal. As the control levels of temperature was 55
      degrees C, 60 degrees C, 65 degrees C during composting, the ratios of wastes
      reduction were 45.8%, 63% and 58.1%, respectively. And the ratiosof wastes
      biodegradation were 23.4%, 41.4% and 23.8%, respectively. And the ratios of water
      removal were 59.9%, 79.1% and 78%, respectively. It was the most effective to
      control temperature of composting on about 60 degrees C among the three control
      levels of temperature trials, either base of biodegradation or moisture removal.
      The control temperature of 65 degrees C also have a powerful ability of moisture
      removal, but its biodegradation is not so efficient as that of 60 degrees C. The
      control temperature of 55 degrees C have the worst ability to reducing wastes,
      degrading organic matter and removing water during the co-composting of vegetable
      and flower wastes.

PMID- 16599144
TI  - [Application of white-rot fungi in composting lead-contaminated waste].
AB  - Simulative lead polluted wastes which containing unpolluted soil, household
      waste, straw, bran and lead nitrate were prepared. Inoculation of white-rot fungi
      and uninoculation in composting of lead-contaminated waste were studied. Change
      of chemical factor, biological parameter and biological toxicity analyses with
      time during the composting process were determined to study effect of heavy metal
      on composting process and probability of application of white-rot fungi in
      composting of metal-contaminated waste. The results show the composting of lead
      contaminated waste inoculated white-rot fungi could be successfully processed,
      which lead to the reduction of the bioavailability of Pb in compost and alleviate
      the potential harm from heavy metal. Under this composting process, for the final
      compost, pH, water-soluble organic carbon/nitrogen, volatile solid, lignin and
      coarse fibre remained reached 7.9, 4.01, 36.1%, 22.4g, 30.1g, respectively. In
      addition, 63.38% of Pb in residual fraction and 0% of Pb in soluble-exchangeable
      fraction were found in final compost, and the germination index of final compost
      reached 121%.

PMID- 16599145
TI  - [Comparison of two types of double-lined simulated landfill leakage detection
      based on high voltage DC method].
AB  - Two types of double high density polyethylene (HDPE) liners landfill that clay or
      geogrid was added between the two HDPE liners. The general resistance of the
      second mode is 15% larger than the general resistance of the first mode in the
      primary HDPE liner detection, and 20% larger than that of the first one in the
      secondary HDPE liner detection. High voltage DC method can accomplish the leakage
      detection and location of these two types of landfill and the error of leakage
      location is less than 10cm when electrode space is 1m.

PMID- 16599146
TI  - [Effects of leachate recirculation volume on its characteristic and landfill
      stabilization rate].
AB  - Impacts of recirculation volume on leachate characteristic and landfill
      stabilization rate were studied. Four simulated bioreactor landfill columns were
      operated weekly with different recirculation ratios, respectively 5.3%, 2.7%,
      0.67% leachate and 0.33% water, in this comparative research. The results
      indicate that simulated reactor with 5.3% recirculation ratio has the most
      rapidly stabilization rate and release the most organic pollutant. The shortest
      methane generation delay was also observed in this column. While simulated
      reactor with 2.7% recirculation ratio formed the best microbe environment and
      kept the highest reactor temperature 35 degrees C. It also had the best impactive
      load capacity and treating efficiency to leachate, and removal of COD was 77% and
      BOD5 was 88% respectively. In actual projects, appropriate leachate recirculation
      volume should be chosen according to design purpose of landfill sites.

PMID- 16599147
TI  - [Chemical stabilization technology in treating with flyash using apatite].
AB  - Toxicity leaching characteristics and chemical compositions of sample flyash
      collected from municipal solid waste incinerator was analyzed, it was clear that
      different heavy metals were contained in flyash and the heavy metal leaching
      concentration for Pb, Zn, Cd was 11.8, 164.9 and 31.2 mg/L respectively which was
      much higher than that in Hazardous Waste Toxicity Leaching Standards. A new kind
      of inorganic chemical agent apatite was chosen to treat with this kind of
      incineration flyash, the results indicate that the heavy metals (not including Cd
      in some samples) in the treated flyash using apatite at dosage 7% can reach the
      landfilling standards for hazardous waste, and the treated flyash can have better
      stabilization when the size of apatite was 74 microm, and the heavy metal
      leaching concentration of the treated flyash keep stable at a curing time of 1
      day, and it can keep stabilization with a broader pH value of 3 to 11. Thus the
      risk of secondary pollution for the treated flyash was reduced dramatically when
      the environment conditions change.

PMID- 16599148
TI  - Seasonal and geographical distribution of adult Ixodes scapularis say (Acari:
      Ixodidae) in Louisiana.
AB  - The distribution and seasonality of adult black-legged ticks (Ixodes scapularis
      Say) in Louisiana was measured. The presence of adult ticks was determined by
      flagging at 106 sites throughout Louisiana. It was concluded that Ixodes
      scapularis is widely distributed throughout Louisiana. Ticks were also collected
      twice per month at one site over a 15-month period by flagging and use of CO2
      traps to establish the relative seasonal abundance pattern of free-living adult
      ticks. Host-seeking, black-legged adult ticks were collected from October to May.
      Peak adult abundance was observed in December. More ticks were collected by the
      use of CO2 traps compared to flagging in October, November, and February. No
      black-legged tick larvae or nymphs were collected in this study using either
      collection method.

PMID- 16599149
TI  - Tick infestations of the eastern cottontail rabbit (Sylvilagus floridanus) and
      small rodentia in northwest Alabama and implications for disease transmission.
AB  - Studies were conducted over a four-county area of northwest Alabama to determine
      the association of eastern cottontail rabbits with Dermacentor variabilis, the
      eastern United States vector of Rocky Mountain spotted fever. A secondary
      objective was to compare infestations of this tick on rabbits with infestations
      on commonly encountered rodent species as a means of determining the relative
      importance of each in the disease transmission cycle. These epidemiologic surveys
      were conducted in response to reported fatal cases of Rocky Mountain Spotted
      Fever in two counties of the study area. From 202 eastern cottontail rabbits,
      3,956 ticks were collected. Of this total, 79.87% were Haemphysalis
      leporispalustris, 9.15% Amblyomma americanum, 8.22% Ixodes dentatus, and 2.76% D.
      variabilis. Only immature stages of D. variabilis were collected from cottontail
      rabbits. Ticks were collected on rabbits in all months except November, and only
      one specimen was taken in January. Based on the average number of ticks per host
      collected in each month, April was the peak month for D. variabilis and I.
      dentatus. High values for H. leporispalustris also occurred at this time, but
      even higher values occurred in October and December. The heaviest infestation of
      A. americanum occurred during the month ofAugust and coincides with the activity
      period for the larvae of this species. Two hundred sixty-nine of the smaller
      Rodentia, comprising 13 species, yielded 264 ticks, all D. variabilis, and all
      but two were immature stages. Five rodent species, Microtus ochragaster Orozomys
      palustris, Peromyscus gossypinus, Peromyscus leucopus, and Sigmodon hispidus
      accounted for 95.83% of the ticks collected, and appeared to be preferred hosts
      for D. variabilis; all five had higher infestation levels per host than did the
      eastern cottontail rabbit. Data on host relationships in association with
      seasonal activity are presented.

PMID- 16599150
TI  - Field trial on the spatial repellency of metofluthrin-impregnated plastic strips
      for mosquitoes in shelters without walls (beruga) in Lombok, Indonesia.
AB  - Field trials on the spatial repellency of metofluthrin-impregnated plastic strips
      for mosquitoes present in shelters without walls (beruga) were carried out in
      Lombok, Indonesia. A major reduction in the incidence of human biting by Culex
      quinquefasciatus was achieved, and the use of two strips per beruga repelled >60%
      of the mosquitoes for at least 11 wk while four strips repelled >60% of the
      mosquitoes for more than 15 weeks. The technique was found to be a practical long
      term solution for the prevention of mosquito bites without using electricity or
      heat to evaporate the metofluthrin.

PMID- 16599151
TI  - Seasonal dynamics of four potential West Nile vector species in north-central
      Texas.
AB  - A population survey was conducted from April through September 2002 on mosquito
      species occurring on the Ray Roberts Greenbelt, a riparian corridor used for
      public recreation on the Elm Fork of the Trinity River, in Denton County, TX.
      Geographic information system software was used to set up a stratified random
      sampling design based on habitat parameters. Mosquitoes were collected using
      light traps, gravid traps, and resting boxes. A total of 29 species was collected
      during this study belonging to the following genera: Aedes, Anopheles,
      Coquillettidia, Culex, Mansonia, Ochlerotatus, Orthopodomyia, Psorophora, and
      Uranotaenia. The four most common species collected during this study were Aedes
      vexans, Culex erraticus, Culex salinarius, and Psorophora columbiae. West Nile
      virus (WNV) has been detected in these species in the United States, and they may
      serve as important vector species in Denton County. Collections were analyzed by
      the Texas Department of Health for arboviruses. One pool consisting of both Cx.
      erraticus and Cx. salinarius, collected in August 2002, tested positive for WNV,
      making it the first mosquito pool to test positive for WNV in Denton County.
      Canonical correspondence analysis was performed using abundance data of dominant
      species with selected weather variables and habitat parameters. Important factors
      for determining dominant species abundance were temperature, precipitation, dew
      point, and canopy coverage. Spatial and temporal patterns of these species are
      discussed.

PMID- 16599152
TI  - Mosquito larvicidal activity of aqueous extracts of long pepper (Piper
      retrofractum vahl) from Thailand.
AB  - Aqueous extracts of nine medicinal plants were bioassayed against larvae of Culex
      quinquefasciatus Say and Aedes aegypt (L.). Among these plants, the long pepper,
      Piper retrofractum Vahl (Piperaceae), showed the highest level of activity
      against mosquito larvae. To gain more information on larvicidal activity of P.
      retrofractum, fresh fruits of this plant were extracted in water and the extracts
      made into powder and bioassayed against 3rd and 4th instar larvae of Cx.
      quinquefasciatus and Ae. aegypti in the laboratory. Extracts of unripe (001/3)
      and ripe (002/3 and 001/4) fruits showed different levels of activity against Cx.
      quinquefasciatus larvae. Extracts 001/3 and 002/3 were equi-toxic to a Bacillus
      sphaericus resistant and susceptible strains, both from Thailand. The ripe fruit
      extract 002/3 was somewhat more active against Ae. aegypti than Cx.
      quinquefasciatus. Another ripe fruit extract (001/4) was much more toxic to both
      mosquito species. Diluted solutions of the solid extract (002/3) in distilled
      water lost their larvicidal activity upon aging. Loss of activity at 25 degrees C
      was greater than that stored at 4 degrees C, and greater in water than in acetone
      solution.

PMID- 16599153
TI  - Host plant selection of two Mansonia blanchard species (Diptera: Culicidae) in a
      heterogeneous habitat of Buenos Aires City, Argentina.
AB  - Larvae and pupae of the genus Mansonia Blanchard attach to the roots of aquatic
      plants by means of modified structures to obtain oxygen. A study of the
      association of larval Ma. indubitans and Ma. titillans with floating macrophytes
      was conducted at Macies Pond, Argentina. Fifty-four sampling units were taken
      from January to May 2003. Three genera of host plants were considered: Pistia,
      Limnobium, and Salvinia. A total of 402 immatures of Ma. indubitans and 217 of
      Ma. titillans were captured and associations between Mansonia immatures and roots
      of each genera were assesed. Significant association was noted between Ma.
      indubitans and certain host plant species (K-W H=42.74, df=2, p<0.001). The same
      result was observed for Ma. titillans (K-W H=23.42, df=2, p<0.001). Both Mansonia
      species utilized roots of P. stratiotes in significantly higher proportions than
      expected by random selection. Both species showed significant negative
      association with Salvinia spp., while no clear relationships were detected with
      L. laevigatum.

PMID- 16599154
TI  - Variability in natural populations of Anopheles sacharovi (Diptera: Culicidae)
      from southeast Anatolia, revealed by morphometric and allozymic analyses.
AB  - Four populations of Anopheles sacharovi Favre occurring in different ecological
      subregions at altitudes between 353-1,126 m in the Sanliurfa Province of
      southeast Turkey were compared using morphometric and allozyme analyses. Four
      allozyme loci were assessed for genetic differentiation among samples from four
      localities. The similarity phenogram obtained from the allozyme data showed that
      populations at Birecik and Sandi branched as a separate group from the Pamuklu
      and Gedik populations. The Gedik population at the highest altitude (1,126 m) was
      clustered as a separate branch when linear measurements of 63 morphological
      characteristics were examined. The UPGMA phenogram also showed that Pamuklu and
      Sandi formed a cluster while Birecik and Gedik formed separate groups.

PMID- 16599155
TI  - Evidence to support two conspecific cytological races on Anopheles aconitus in
      Thailand.
AB  - Iso-female lines (isolines) of Anopheles aconitus collected from Mae Hong Son,
      Phet Buri, and Chiang Mai Provinces were successfully identified to karyotypic
      forms. The results of identification revealed that An. aconitus Form B (X1, X2,
      Y2) was obtained from four and 48 isolines in Phet Buri and Chiang Mai Provinces,
      respectively, and Form C (X1, X2, Y3) was recovered from three and 41 isolines in
      Mae Hong Son and Chiang Mai Provinces, respectively. When comparing band to band
      on the same arm of ovarian nurse cell polytene chromosomes of An. aconitus Form B
      (Phet Buri: four isolines) and C (Mae Hong Son: three isolines, Chiang Mai: 20
      isolines) to the standard chromosome mapping of An. aconitus Form B (Chiang Mai:
      20 isolines), no major chromosomal rearrangements that related to the karyotype
      variations were demonstrated. The investigations on allelic frequencies of 4th
      stage larvae and adult females of three (Form C: Mae Hong Son), four (Form B:
      Phet Buri), 41 (Form C: Chiang Mai) and 48 (Form B: Chiang Mai) isolines
      suggested that An. aconitus Form B and C of all strains have similar allelic
      frequencies. This was observed at 10 isoenzymes 16 loci in 4th stage larvae, and
      11 isoenzymes 13 loci in adult females. Hybridization tests among the four
      laboratory-raised isolines of An. aconitus Form B (Chiang Mai and Phet Buri) and
      C (Chiang Mai and Mae Hong Son) were employed by induced copulation. The results
      of crosses indicated that they were genetically compatible, providing viable
      progeny and completely synaptic salivary gland polytene chromosomes. The complete
      sequences ofrDNA internal-transcribed spacer two (ITS2) and partial sequences of
      mitochondrial cytochrome c oxidase subunit I and II (COI and COII) from genomic
      DNA of 12 isolines of An. aconitus Form B and C were identified. Total sequence
      lengths (ITS2+COI+COII) of An. aconitus isolines varied from 1550bp to 1556bp.
      Conspecific relationships between the two An. aconitus forms were well supported
      by low values of intraspecific distances (ranged from 0.1% to 1.0%) and genetic
      differentiation (d(xy): 0.01322) between the two forms. Based on evidence of no
      pre- and post-mating isolations, and nearly identical of DNA sequences of ITS2,
      COI and COII regions between An. aconitus Form B and C, we conclude that they are
      conspecific cytological races in the Thai population.

PMID- 16599156
TI  - Geographical distribution of Anopheles minimus species A and C in western
      Thailand.
AB  - Elucidating vector distribution based on an accurate species identification is
      important to understanding the nature of the species complex in order to achieve
      vector control. Morphologically, An. minimus s.l. is difficult to distinguish
      from both its species complex and its closely related species. A polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) technique and a
      single multiplex-allele specific PCR developed for species identification were
      applied in this study in comparison with morphological identification. Both
      methods were used, combining with geographical information systems to determine
      the distribution of An. minimus species A and C. The investigation on the
      breeding habitats was performed in the malarious area of western Thailand.
      Anopheles larvae were collected from 36 bodies of water among five districts
      (Sangkhaburi, Thong Pha Phum, Si Sawat, Muang, and Sai Yok) of Kanchanaburi
      Province, Thailand. In this study, An. minimus A larvae were present in all study
      districts but the association differed when focusing on study sites within each
      district. Although there were many reports of An. minimus A in Ban Phu Rat and
      Ban Phu Toei villages in Sai Yok District, we did not find the breeding sites of
      species A in those two areas. An. minimus A and C were found in Ban Phu Ong Ka
      village in Sai Yok District. The breeding habitats of An. minimus C were present
      covering 30-40 km of distance in northern part of Sai Yok and this species was
      also found in the central and southern parts of Si Sawat District.

PMID- 16599158
TI  - Evaluation of habitat management strategies for the reduction of malaria vectors
      in northern Belize.
AB  - Mowing and burning of emergent vegetation were evaluated as potential management
      strategies for the control of the malaria vector, Anopheles vestitipennis, in
      northern Belize, Central America. The primary aim was reduction of tall dense
      macrophytes (dominated by Typha domingensis) as preferred larval habitat for An.
      vestitipennis. Nine experimental plots were established in a Typha marsh in
      Orange Walk District, Belize. Three plots were burned, three were treated by
      subaquatic mowing, and three were unaltered controls. After treatment, Typha
      height was most dramatically affected by the mow treatment. Plant heights at 21
      and 95 days post-treatment reflected an 89% and 48% decrease, respectively,
      compared to pretreatment conditions. The Typha height in the burn plots was not
      as severely affected. Heights at 21 days post-treatment were 39% lower than those
      of pre-treatment vegetation, with a return to near pre-test heights by 95 days
      post-treatment. Both treatments resulted in a significant reduction in the number
      of An. vestitipennis larvae collected as compared to control plots. Conversely,
      the treatments resulted in increased larval densities of several other vector and
      pest mosquito species. Larval population densities ofAn. albimanus, Ochlerotatus
      taeniorhynchus, and Culex coronator were significantly higher in burn plots. In
      mow plots, there were significant increases in An. albimanus and Oc.
      taeniorhynchus larval populations. Non-target invertebrate species affected by
      the treatments were adult Tropisternus collaris, larval Corythrella, and adult
      Parapleapuella.

PMID- 16599157
TI  - Repellent effect of plant essential oils against Aedes albopictus.
AB  - Six essential oils: asteraceae oil, rutaceae oil, mentha piperta oil, carvacryl
      oil, citronella oil, and eucalyptus oil were tested for evaluation of their
      repellent effects against Aedes albopictus mosquitoes under laboratory
      conditions. Only citronella oil and eucalyptus oil were tested with human beings.
      There was considerable protection for mice. Carvacryl oil (7%) provided 100%
      protection for mice after 7 h. Eucalyptus oil (15%) gave protection to humans for
      least 3 h; the protection time was prolonged to 5 h after adding 5% vanillin. The
      mixture could be developed into a practical product after the field evaluation.

PMID- 16599159
TI  - Methods for monitoring outdoor populations of house flies, Musca domestica L.
      (Diptera: Muscidae).
AB  - Relative collections of house flies were compared on two Florida dairy farms
      using several monitoring methods: sticky cylinders, baited jug traps (Farnam
      Terminator and Victor Fly Magnet), and bait strips (Wellmark QuikStrike). Bait
      strips were placed over collecting pans and under 61 cm square plywood roofs to
      protect the toxicant from sunlight ("sheltered QuikStrike traps"). Sticky
      cylinders collected the fewest flies (515-679 flies/trap/day) and sheltered
      QuikStrike traps the most (5,659-8,814 flies/trap/day). The sheltered QuikStrike
      traps are promising tools for disease surveillance programs. The two baited jugs
      collected a similar and intermediate number of flies, with collections highest
      during the first 2 days after placement (2,920-5,462 flies/trap/day). Jug trap
      collections were low after 4 days of use in the field, apparently due to
      deterioration in the attractiveness of the bait over time. Jug traps collected
      mostly females, whereas sticky cylinders and sheltered QuikStrike traps collected
      mostly males. Exposure of jug trap bait (Farnam) to fly cadavers for 3 days did
      not increase attractiveness of the bait. Combinations of the Farnam and Victor
      attractants were more attractive than either attractant alone and 25-43% more
      attractive than expected based on the sum of collections in the single-attractant
      jug traps. A 25% solution of farm-grade blackstrap molasses was as effective as
      either of the two proprietary baits tested, offering a low-cost alternative for
      fly population monitoring.

PMID- 16599160
TI  - Bionomics and distribution of species of Hystrichopsylla in Arizona and New
      Mexico, with a description of Hystrichopsylla dippiei obliqua, n. ssp.
      (Siphonaptera: Hystrichopsyllidae).
AB  - More than 450 specimens of Hystrichopsylla were collected from nests and hosts of
      species of Microtus, Neotoma, Tamiasciurus, and Peromyscus in Arizona and New
      Mexico from 1981-2004. A new subspecies, Hystrichopsylla dippiei obliqua, is
      described and a map illustrating the distribution of the three taxa
      (Hystrichopsylla dippiei truncata Holland, H. d. obliqua, and H. occidentalis
      sylvaticus Campos and Stark) occurring in Arizona and New Mexico is provided.
      Hystrichopsylla. o. sylvaticus is reported in New Mexico for the first time and
      H. d. truncata is a new record in Rio Aribba County, NM. Relationships of Mexican
      species are also discussed. These large fleas are seldom collected from the fur
      of their mammalian hosts (usually singly) but are prevalent in moist nests. The
      maximum number of the new subspecies collected from a single nest was 54. Dry
      nests, particularly those that are not subterranean or otherwise protected from
      desiccation, do not support development of Hystrichopsylla fleas. Minimum
      elevation at which H. dippiei ssp. is found in Arizona and New Mexico appears to
      be about 2,100 m.

PMID- 16599162
TI  - An annotated checklist of the Anopheles mosquitoes (Diptera: Culicidae) in Iran.
AB  - An annotated checklist of the Anopheles mosquitoes in Iran is provided. The list
      is based on data contained in Iranian manuals and reports and information
      published elsewhere. Supplementary information is provided for 24 species.

PMID- 16599161
TI  - Abundance and diversity of human-biting flies (Diptera: Ceratopogonidae,
      Culicidae, Tabanidae, Simuliidae) around a nickel-copper smelter at Monchegorsk,
      northwestern Russia.
AB  - In the summers of 2001 and 2002, we quantitatively sampled human-biting flies in
      twelve sites located 1.6 to 63 km from a large copper-nickel smelter at
      Monchegorsk on the Kola Peninsula, Russia. We collected 429 specimens of three
      species of Ceratopogonidae, 92 specimens of seven species of Culicidae, 76
      specimens of seven species of Tabanidae, and 4,788 specimens of 19 species of
      Simuliidae. Culicoides chiropterus was for the first time reported from the Kola
      Peninsula. Catches of Culicidae and Simuliidae decreased near the smelter,
      presumably due to the combined action of toxicity of pollutants, pollution
      induced forest damage, and decline in vertebrate density. An abundance of
      Ceratopogonidae and Tabanidae, the size of the most common black fly species,
      Simulium pusillum, and the diversity of all families did not change along the
      pollution gradient.

PMID- 16599163
TI  - Evaluation of the present dengue situation and control strategies against Aedes
      aegypti in Cebu City, Philippines.
AB  - The present dengue situation and methods to control Aedes aegypti larvae in Cebu
      City, Philippines, were evaluated for the development of an integrated community
      based dengue control program. The study included the detection of dengue
      infection among Filipino patients, surveying mosquito breeding sites to determine
      larval population density of Aedes aegypti, an evaluation of public knowledge,
      attitude, and personal protection practices against dengue, and an evaluation of
      the efficacy of VectoBac DT/Culinex Tab tablets based on Bacillus thuringiensis
      israelensis against Ae. aegypti larvae. Of the 173 human sera samples that were
      assayed for dengue viruses, 94.9% were positive, 2.2% negative and 2.8%
      equivocal. Thirty households were randomly chosen per Barangay "Villages" (lowest
      level of formal local administration). Of the 489 breeding sites surveyed, 29.4%
      were infested with Ae. aegypti larvae, with discarded tires having the highest
      infestation rate (69.4%). A survey of people's knowledge, attitude, and practices
      for integrated community-based dengue control showed that 68.7% of the
      interviewees were aware that dengue is transmitted by mosquitoes, but only 4.3%
      knew that a virus was the cause of the disease. The efficacy of one and two
      tablets of VectoBac DT/Culinex Tab, based on Bacillus thuringiensis israelensis,
      was assessed against the larvae of Ae. aegypti exposed to sunshine and shaded
      water containers in semi-field and field tests. In semi-field tests, 100%
      mortality was achieved until the 18th and 30th day after the application of one
      and two tablets, respectively, in sun-exposed containers. In shaded containers,
      100% mortality was observed until the 30th and 36th day after the application of
      one and two tablets, respectively. In field tests, the tablets were effective for
      approximately 3 weeks.

PMID- 16599164
TI  - Synergistic efficacy of botanical blends with and without synthetic insecticides
      against Aedes aegypti and Culex annulirostris mosquitoes.
AB  - Increasing insecticide resistance requires strategies to prolong the use of
      highly effective vector control compounds. The use of combinations of
      insecticides with other insecticides and phytochemicals is one such strategy that
      is suitable for mosquito control. In bioassays with Aedes aegypti and Culex
      annulirostris mosquitoes, binary mixtures of phytochemicals with or without
      synthetic insecticides produced promising results when each was applied at a LC25
      dose. All mixtures resulted in 100% mortality against Cx. annulirostris larvae
      within 24 h rather than the expected mortality of 50%. All mixtures acted
      synergistically against Ae. aegypti larvae within the first 24 h except for one
      mixture that showed an additive effect. We conclude that mixtures are more
      effective than insecticides or phytochemicals alone and that they enable a
      reduced dose to be applied for vector control potentially leading to improved
      resistance management and reduced costs.

PMID- 16599165
TI  - Patterns of insecticide resistance in larval Culex pipiens populations in Israel:
      dynamics and trends.
AB  - Resistance to insecticides of larval Culex pipiens populations in Israel has been
      monitored for ten years and the results were used for control planning. The
      insecticides tested were the organophosphates chlorpyrifos, fenthion, and
      temephos and the pyrethroids permethrin and cypermethrin. Over the years the
      relative resistance (R/R) values to chlorpyrifos in most populations tested were
      between 200-400, with records of up to 700 R/R. Practically no susceptible
      populations were found and the compound has been withdrawn from use, resulting in
      a decrease in the relative resistance values. In 1996 when fenthion was
      reintroduced, no resistant populations were found, but in the following years
      significant resistance appeared in an increasing number of populations with
      values lower than recorded for chlorpyrifos but still high (up to 100 R/R). All
      populations tested were found to be susceptible to temephos and accordingly the
      compound was reintroduced in 2002. Over the ten years, no significant resistance
      to cypermethrin was found in the majority of the populations tested, while a
      trend of increased resistance to permethrin was noted with a few records of >1000
      R/R. The results demonstrate the importance of continuous monitoring of
      insecticide resistance for efficient mosquito control. Alternative insecticides
      and methods of control are discussed.

PMID- 16599166
TI  - Effects of sub-lethal concentrations of synthetic insecticides and Callitris
      glaucophylla extracts on the development of Aedes aegypti.
AB  - Synthetic and botanical insecticides can have a profound effect on the
      developmental period, growth, adult emergence, fecundity, fertility, and egg
      hatch, resulting in effective control at sub-lethal concentrations. This paper
      investigated sub-lethal concentrations of fenitrothion, lambda-cyhalothrin, and
      Callitris glaucophylla Joy Thomps. & L.P. Johnson (Cupressaceae) extract to
      characterize their effects on the development of Aedes aegypti L. (Diptera:
      Culicidae) mosquito larvae. The LC25, LC50, and LC75 (four replicates) were used
      for each synthetic insecticide and the LC25 and LC75 (four replicates) were used
      for C. glaucophylla. Observations of larval mortality, duration of larval stage,
      pupal mortality, duration of pupal stage, adult emergence, sex ratio, and
      malformations were recorded over 14 days. A dose-response effect was observed for
      all insecticides. Although C. glaucophylla extract doses were higher than
      synthetic insecticide doses, the LC75 treatment outperformed synthetics by
      completely prohibiting adult emergence. Consequently, this botanical is
      recommended for field application either in combination with synthetic or natural
      insecticides or alone.

PMID- 16599167
TI  - Chemical detection of the predator Notonecta irrorata by ovipositing Culex
      mosquitoes.
AB  - We tested the oviposition response of Culex mosquitoes to the predator Notonecta
      irrorata in an outdoor artificial pool experiment employing equal numbers of
      control and predator pools. There was a strong oviposition avoidance by Culex of
      Notonecta pools; 83% of egg rafts were found in control pools during the period
      in which Notonecta were present. After removing Notonecta, mosquitoes continued
      to avoid ovipositing in the former Notonecta pools for two additional days
      suggesting a predator-released kairomone as the cue used by the mosquitoes to
      detect the presence of this predator.

PMID- 16599168
TI  - Chemical composition and anti-mosquito potential of rhizome extract and volatile
      oil derived from Curcuma aromatica against Aedes aegypti (Diptera: Culicidae).
AB  - Crude rhizome extracts and volatile oils of Curcuma aromatica were evaluated for
      chemical composition and anti-mosquito potential, including larvicidal,
      adulticidal, and repellent activities against the Aedes aegypti mosquito.
      Chemical identification achieved by GC/MS analysis revealed that xanthorrhizol,
      1H-3a, 7-methanoazulene and curcumene at 35.08 and 13.65%, 21.81 and 30.02%, and
      13.75 and 25.71%, were the main constituents in hexane extracts and volatile
      oils, respectively. Volatile oil of Cu. aromatica possessed a significantly
      higher larvicidal activity against the 4th instar larvae of Ae. aegypti than that
      of hexane extracts, with LC50 values of 36.30 and 57.15 ppm, respectively. In
      testing for adulticidal activity, on the other hand, hexane-extracted Cu.
      aromatica (LC50: 1.60 microg/mg female) was found to be slightly more effective
      against female Ae. aegypti than volatile oil (LC50: 2.86 microg/mg female).
      However, the repellency of these two products against Ae. aegypti adult females
      differed significantly. The hexane-extracted Cu. aromatica, with a median
      complete protection time of 1 h (range = 1-1.5 h) when applied at a concentration
      of 25%, appeared to have significantly higher repellency than that of distillate
      oil (0.5 h, range = 0-0.5 h). The different results obtained from both products
      of Cu. aromatica were probably due to variety in quantity and type of active
      ingredients as well as the biological and physiological characteristics that
      differed between both developmental stages of mosquitoes, larvae, and adults.

PMID- 16599170
TI  - Seasonal abundance of horse flies (Diptera: Tabanidae) from two locations in
      eastern Croatia.
AB  - A total of 10,539 tabanid horse flies from 22 species and five genera was
      collected in the Tikves forest within the Kopacki rit Nature Park in eastern
      Croatia. Seasonal abundance was analyzed for the six most abundant species.
      Tabanus maculicornis, Tabanus tergestinus, and Haematopota pluvialis reached
      their highest peak abundance in the fourth week of June. Atylotus loewianus and
      Tabanus bromius reached their highest peak of abundance in the first week of
      August, whereas Tabanus sudeticus reached its maximum abundance in the third week
      of July. Horse flies also were collected once a week on the pasture at Petrijevci
      from mid-May to mid-September during 1993. Paired collections were made from a
      Malaise trap and from a horse by using a sweep net. A total of 2,867 tabanids
      belonging to 26 species was collected. The number of tabanids collected on horses
      was much higher than the total captured with Malaise traps. On their natural host
      (horse), 2.6 times more tabanids were collected than in the traps. Seasonal
      abundance was analyzed only for the eight most abundant species. Chrysops
      paralellogrammus, Tabanus autumnalis, Tabanus bromius, Tabanus tergestinus,
      Haematopota pluvialis, and Haematopota subcylindrica all reached their highest
      peak of abundance in the second week of July, whereas Tabanus maculicornis
      reached the maximal peak of abundance in the third week of June. Seasonal
      meteorological variability that occurs periodically from one year to another has
      a significant influence on the maximal peaks of tabanid abundance.

PMID- 16599169
TI  - Bartonella and Rickettsia in fleas and lice from mammals in South Carolina,
      U.S.A.
AB  - Species in the genera Bartonella and Rickettsia are vector-borne pathogens of
      humans and domestic animals. The natural reservoirs and enzootic transmission
      cycles of these bacteria are poorly known in South Carolina. Thirteen species of
      lice and fleas were collected from urban animals and screened for the presence of
      Bartonella and Rickettsia by PCR amplification using genus-specific primers.
      Bartonella henselae was present in cat fleas (Ctenocephalides felis) from
      Virginia opossums (Didelphis virginiana) and a novel genotype of Bartonella was
      detected in Orchopeas howardi from an eastern gray squirrel (Sciurus
      carolinensis). We detected R. typhi and three novel genotypes Rickettsia in other
      species of fleas and lice. Rickettsia typhi, the causative agent of murine
      typhus, was detected in two pools of lice (Enderleinellus marmotae) from the
      woodchuck (Marmota monax). Cat fleas harbored one of two novel genotypes of
      Rickettsia. A third novel Rickettsia was detected in Orchopeas howardi from an
      eastern gray squirrel.

PMID- 16599171
TI  - Relative abundance of mosquito species (Diptera: Culicidae) on Big Pine Key,
      Florida, U.S.A.
AB  - Species diversity of mosquito (Diptera: Culicidae) collections in carbon dioxide
      baited light traps was investigated on Big Pine Key, Florida, from 2000 - 2004.
      Twenty species of mosquitoes were collected during this study, the most commonly
      collected being Anopheles atropos, Culex bahamensis, Deinocerites cancer, and
      Ochlerotatus taeniorhynchus. Ochlerotatus taeniorhynchus is the dominant species
      at this location. For most of the mosquito species, more individuals were
      collected during the "high season" months (June to September) than in the "low
      season" months (January to March). During most years more mosquito species were
      collected in the high season than in the low season. Rank order of species
      collected was significantly correlated between low and high season. Species
      composition at this site appears to be relatively stable from year to year and
      from season to season.

PMID- 16599172
TI  - Laboratory estimation of degree-day developmental requirements of Phlebotomus
      papatasi (Diptera: Psychodidae).
AB  - Cutaneous leishmaniasis is one of the most important vector-borne endemic
      diseases in Turkey. The main objective of this study was to evaluate the
      influence of temperature on the developmental rates of one important vector of
      leishmaniasis, Phlebotomus papatasi (Scopoli, 1786) (Diptera: Psychodidae). Eggs
      from laboratory-reared colonies of Phlebotomus papatasi were exposed to six
      constant temperature regimes from 15 to 32 degrees C with a daylength of 14 h and
      relative humidity of 65-75%. No adult emergence was observed at 15 degrees C.
      Complete egg to adult development ranged from 27.89 +/- 1.88 days at 32 degrees C
      to 246.43 +/- 13.83 days at 18 degrees C. The developmental zero values were
      estimated to vary from 11.6 degrees C to 20.25 degrees C depending on life
      stages, and egg to adult development required 440.55 DD above 20.25 degrees C.

PMID- 16599173
TI  - Vertical distribution of adult mosquitoes in native forest in Auckland, New
      Zealand.

PMID- 16599174
TI  - Outbreak of dengue in national capital territory of Delhi, India during 2003.

PMID- 16599175
TI  - Molecular evidence for novel bartonella species in Trichobius major (Diptera:
      Streblidae) and Cimex adjunctus (Hemiptera: Cimicidae) from two southeastern bat
      caves, U.S.A.

PMID- 16599176
TI  - A method for determining the sex of larval Aedes aegypti mosquitoes.

PMID- 16599177
TI  - The use of an experimental hut for evaluating the entering and exiting behavior
      of Aedes aegypti (Diptera: Culicidae), a primary vector of dengue in Thailand.

PMID- 16599178
TI  - First occurrence of Ochlerotatus japonicus in Missouri.

PMID- 16599179
TI  - XCPT (accept) software: the future of case-analysis and patient acceptance of
      treatment planning.

PMID- 16599180
TI  - Influenza viruses and their ion channels.
AB  - Influenza is an ancient disease that has infected humans in irregular intervals
      throughout recorded history. The most infamous pandemic was "Spanish Flu" which
      affected large parts of the world population and killed in 1918-1919, at a rough
      estimate, at least 50 million people. More recently, two influenza A pandemics
      occurred in 1957 ("Asian influenza") and 1968 ("Hong Kong influenza") and caused
      significant morbidity and mortality globally. Most recently, in 1997 and 2003,
      limited outbreaks caused by a new influenza A virus subtype H5N1 that was
      directly transmitted from birds to humans, occurred in the Hong Kong Special
      Administrative Region of China. Since 2003, the avian H5N1 strain has infected
      more then 130 persons in Vietnam, Thailand, and Cambodia and has killed more than
      half of them. To prevent the human and economical losses caused by human and
      avian influenza viruses, it is necessary to prepare safe universal influenza
      vaccines. In order to develop a broad-spectrum protection against different
      influenza virus strains or variants, some recent studies have were aimed at the
      M2 protein of Influenza A virus. This review compares the influenza A, B, and C
      viruses by focusing on their ion channels.

PMID- 16599181
TI  - Characterization of Autographa californica multiple nucleopolyhedrovirus ORF17.
AB  - The expression of Autographa californica multiple nucleopolyhedrovirus (AcMNPV)
      ORF17 was examined. The respective transcript of 492 nts could be detected by RT
      PCR at 3-72 hrs p.i., while the corresponding protein could be assessed by
      Western blot analysis at 6-72 hrs p.i. Its size was determined at about 19 K in
      agreement with the predicted value of 18.5 K, suggesting that no major
      posttranslational modification of primary gene product. The ORF17 protein was
      primarily located in the cytoplasm. All these results together with earlier data
      on early AcMNPV promoter motifs suggest that ORF17 as an early gene encoding a
      protein located in the cytoplasm of infected cells.

PMID- 16599182
TI  - Influence of guanidine on proteinase K resistance in vitro and infectivity of
      scrapie prion protein PrP(Sc).
AB  - As the scrapie prion protein PrP(Sc) is rich in beta-sheets it aggregates into
      prion rods, which show infectivity and proteinase K (PK) resistance.
      Consequently, dissociation of prion rods and breakdown of beta-sheets in PrP(Sc)
      by denaturation results in loss of both infectivity and PK-sensitivity. In this
      study, the effects of guanidine (Gdn), which solubilizes and denatures proteins
      by breaking down their higher structure, on the solubility, the PK-resistance in
      vitro and the infectivity of PrP(Sc) of scrapie strain 263K was examined. The
      infectivity was assayed by intracerebral inoculation into hamsters. Brain tissues
      of scrapie-infected hamsters were used for preparation of homogenates and crude
      extracts of PrP(Sc). A treatment of PrP(Sc) with Gdn enhanced its PK-sensitivity
      in a dose-dependent manner. The PK-resistance in vitro of PrP(Sc) denatured with
      lower concentrations of Gdn (<2.5 mol/l) could partially resume by renaturation.
      Gdn markedly reduced or, at higher concentrations, even destroyed the infectivity
      of PrP(Sc). On the other hand, the infectivity of PrP(Sc) inactivated by
      denaturation could be partially restored by renaturation. These results confirmed
      our assumption that all the alternations in the PK-resistance and the infectivity
      of PrP(Sc) caused by Gdn resulted from changes in its higher structure. However,
      it should be emphasized that a complete loss of PK-resistance of PrP(Sc) may not
      necessarily mean its full non-infectivity.

PMID- 16599183
TI  - Genetic and phylogenetic characterization of rabies virus isolates from wildlife
      and livestock in Paraiba, Brazil.
AB  - Thirty-four rabies virus (RV) isolates from foxes (8), insectivore bats (9),
      cattle (14), sheep (1), a goat (1) and a donkey (1) from Paraiba state,
      northeastern Brazil, were genetically characterized. Sequences of 890 nts of
      nucleoprotein (N) genes of these isolates were analyzed and compared with those
      of other Brazilian isolates characterized earlier. Phylogenetic analysis revealed
      three genetical lineages of RV co-existing in this region. Each lineage was found
      to be associated with particular host species and to circulate independently of
      each other. The first lineage was found in foxes (Dusicyon sp.) and could be
      discriminated from domestic carnivore isolates from Sao Paulo, Goias and Minas
      Gerais in the southern and central Brazil. The second lineage was associated with
      insectivorous bats (Molossus spp.) and differed from vampire bat-associated RV
      isolates. The third lineage was found in livestock and clustered with vampire bat
      associated RV isolates from Sao Paulo, Tocantins, Goias and Matto Grosso. These
      results indicate that RV of these genetic lineages are cocirculating in the
      Paraiba state and that livestock in this region are infected with vampire bat
      associated RV, suggesting that the vampire bat is the main reservoir of livestock
      rabies in this region.

PMID- 16599184
TI  - Genetic analysis of indian bovine viral diarrhea virus 1 isolates in N(pro) and
      entire gene region coding structural proteins.
AB  - Three Indian Bovine viral diarrhea virus 1 (BVDV-1) isolates were analyzed at
      genetic level in N(pro) (viral autoprotease) and entire gene region coding
      structural proteins, namely capsid (C) protein, E(rns), and envelope proteins E1
      and E2. All these isolates were found to be of b subtype based on the entire 504
      nt region of N(pro) and 1119 nt region of E2. However, in comparison with other
      isolates of this subtype, they were allocated inside the BVDV-1 subtype b cluster
      to a separate clade with a longer distance. Of six cysteine residues in N(pro)
      only three were totally conserved in all three isolates. The isolates showed 94.9
      99.3% and 92.2-99.0% identities for the entire C-E2 gene region at nucleotide and
      amino acid levels, respectively. The lowest identity values (88.5-91.7%) were
      observed for E2 amino acid sequences. The identity of the isolates with Osloss, a
      reference BVDV-1 subtype b strain, was in the range of 82.1-89.9% for nucleotide
      and 78.6-89.2% for amino acid sequences in the C-E2 region. The N(pro)/C and
      E(rns)/E1 cleavage sites were highly conserved. The C/E(rns) and E1/E2 cleavage
      sites were more conserved from the N-end of E(rns) and the C-end of El,
      respectively. These findings suggest that some unique mutations have occurred in
      the described Indian BVDV-1 isolates, though they all belong to the BVDV-1
      subtype b.

PMID- 16599185
TI  - Molecular characterization of recent infectious bursal disease virus isolates
      from Malaysia.
AB  - Three isolates of Infectious bursal disease virus (IBDV), designated UPM04178,
      UPM04190 and UPM04238, were obtained from severe outbreaks of infectious bursal
      disease (IBD) in Malaysia in 2004. The hypervariable region (HPVR) of VP2 gene of
      these isolates was sequenced. The obtained sequences were compared with those of
      other isolates. The highest similarity (98%) concerning both nucleotide and amino
      acid sequences was found to very virulent IBDV (vvIBDV) strains. Phylogenetic
      analysis revealed clustering of the three isolates with vvIBDV strains.
      Evolutionary relatedness of the three isolates to vvIBDV strains was demonstrated
      by three phylogenetic methods: bootstrap values of 100%, 95% and 90% for
      nucleotide sequences and those of 58%, 86% and 96% for amino acid sequences were
      obtained by the distance, maximum parsimony and maximum likehood methods,
      respectively. It is concluded that UPM04178, UPM04190 and UPM04238 are vvIBDV
      isolates of serotype 1, which originate from a common ancestor of IBDV strains
      present in Malaysia.

PMID- 16599186
TI  - Lymphocytic choriomeningitis virus mx strain does not induce the expression of
      tumor-associated carbonic anhydrase IX in persistently infected HeLa cells.
AB  - Summary. - Lymphocytic choriomeningitis virus (LCMV) is an arenavirus that
      readily causes persistent infections, in which it does not interfere with vital
      functions of the cells, but can affect expression of "luxurious" genes. MX strain
      of LCMV (MX LCMV) has been identified as an agent transmissible by cell-to-cell
      contact in the human carcinoma MaTu cells grown in a mixed culture with HeLa
      cells. When compared to uninfected HeLa, the MaTu-MX-infected HeLa cells, to
      which the virus was transmitted via co-cultivation with mitomycin C-treated MaTu
      cells, showed an elevated expression of a protein called MN, suggesting that MN
      can be induced by MX LCMV. MN protein was later identified as the carbonic
      anhydrase isoform IX (CA IX), whose expression has been predominantly associated
      with hypoxic tumors of poor prognosis. Since the proposal that MX LCMV can induce
      such a cancer-related protein could substantially change our view on the biology
      of LCMV-host interaction we undertook its verification. Instead of co
      cultivation, we used MaTu cell-free extracts to transmit MX LCMV to HeLa cells.
      These cells were then grown for more than 30 passages, but the level of MN/CA IX
      did not increase throughout the whole cultivation period as compared to
      uninfected HeLa cells. Moreover, a treatment of MaTu-MX-infected HeLa cells with
      ribavirin eliminated the virus, but did not reduce the MN/CA IX expression. Our
      results clearly showed that MN/CA IX is independent of MX LCMV and that the virus
      itself does not influence the MN/CA IX level in HeLa cells.

PMID- 16599187
TI  - Expression of entry receptor nectin-1 of herpes simplex virus 1 and/or herpes
      simplex virus 2 in normal and neoplastic human nervous system tissues.
AB  - Herpes simplex virus 1 and/or Herpes simplex virus 2 (HSV) are important
      pathogens of human nervous system (NS) and genetically modified HSV strains have
      been proposed as vectors for gene therapy targeting the brain and brain tumors.
      Nectin-1 is an immunoglobulin-like adhesion molecule that participates in the
      formation of synapses and serves as an entry receptor for HSV. The expression
      pattern of nectin-1 in normal human NS and brain tumors is not well understood.
      To better understand the nectin-1 expression in normal and neoplastic human NS,
      immunohistochemistry was used to detect the nectin-1 expression in sections of
      normal human brain, spinal cord and trigeminal and dorsal root ganglia (n=10) and
      in sections of primary NS neoplasms (n=22). In normal human NS, nectin-1 was
      detected in the soma and processes of central and peripheral neurons, in
      ependymal cells, choroid plexus epithelial cells, vascular endothelial cells and
      meningothelial cells. Oligodendrocytes, astrocytes, vascular smooth muscle cells,
      and Schwann cells showed variable immunoreactivity. Among tumors, schwannoma,
      fibrous meningioma, and medulloblastoma were nectin-1 negative.
      Oligodendroglioma, ependymoma, pilocytic astrocytoma, pleomorphic
      xanthoastrocytoma, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma
      multiforme and meningothelial meningioma showed weak focal nectin-1-positivity.
      Ganglion cells of ganglioglioma were strongly positive. These studies provide
      novel information about the expression of nectin-1 in normal and neoplastic NS,
      and thus may lead to a better understanding of cell targeting by HSV during HSV
      induced neurological disease and during a HSV-based gene therapy.

PMID- 16599188
TI  - In situ RT-PCR can distinguish between productive and latent cytomegalovirus
      infection in the blood cells of bone marrow transplant recipients.
AB  - Thirty-four peripheral blood leukocyte samples from bone marrow transplant (BMT)
      recipients were examined for Human cytomegalovirus (HCMV) phosphoprotein 65
      (pp65), DNA and late transcripts. Twenty seven samples were positive for pp65 in
      the cytoplasm by immunofluorescent assay (IFA). Viral DNA was confirmed in 26
      samples by nested PCR (nPCR). Using in situ RT-PCR, viral late transcripts were
      found in 19 samples, positive also by IFA and nPCR; these samples were considered
      indicative of productive viral infection. Five samples, positive by nPCR but
      negative by IFA and in situ RT-PCR, were considered to represent latent viral
      infection. In 8 samples, positive by IFA and nPCR but negative by in situ RT-PCR,
      apparently phagocytosis of viral particles took place.

PMID- 16599189
TI  - Contribution to the problem of infection of humans with a murine
      gammaherpesvirus.

PMID- 16599190
TI  - Optimal interpolation method for intercomparison of atmospheric measurements.
AB  - Intercomparison of atmospheric measurements is often a difficult task because of
      the different spatial response functions of the experiments considered. We
      propose a new method for comparison of two atmospheric profiles characterized by
      averaging kernels with different vertical resolutions. The method minimizes the
      smoothing error induced by the differences in the averaging kernels by exploiting
      an optimal interpolation rule to map one profile into the retrieval grid of the
      other. Compared with the techniques published so far, this method permits one to
      retain the vertical resolution of the less-resolved profile involved in the
      intercomparison.

PMID- 16599191
TI  - Vector mode analysis of a young interferometer.
AB  - It is proved that, when the vector modal theory of coherence is applied to a pair
      of fixed points, exact results are obtained for the mode structure. In
      particular, it is shown that the field radiated by the pinholes of a Young
      interferometer can always be represented by the incoherent superposition of no
      more than four perfectly correlated and polarized modes. The role of such modes
      is illustrated through a simple example.

PMID- 16599192
TI  - Measuring spatial coherence by using a reversed-wavefront Young interferometer.
AB  - A very simple optical setup for the measurement of the modulus and the phase of
      the two-point correlation function of a partially coherent light field is
      presented. The system consists of a slightly modified version of a Young
      interferometer and requires a single Young mask in order to determine the
      correlation function at any pairs of points. Experimental results are presented
      for the case of a synthesized partially coherent secondary source.

PMID- 16599193
TI  - Generation of hollow beams by using a binary spatial light modulator.
AB  - We demonstrate the generation of hollow laser beams by using a binary spatial
      light modulator and compare the results with those for a continuous modulator.
      The binary phase modulator produces beams that have continuous, azimuthally
      varying phase profiles and can be dynamically changed with kilohertz refresh
      rates. The intensity and phase profiles are recorded through the focus of an
      imaging lens and are compared with scalar diffraction theory. We highlight
      properties of the beams relevant to optical dipole traps.

PMID- 16599194
TI  - Properties of circularly polarized vortex beams.
AB  - The properties of circularly polarized vortex beams in cylindrical polarization
      bases are studied. A circularly polarized vortex beam is decomposed into radial
      and azimuthal polarization. With the proper combination of vortex charge and the
      handedness of the circular polarization, a focal field with an extremely strong
      longitudinal component as well as a flat-topped profile can be obtained. The
      cylindrical decomposition also sheds light on the connections between orbital
      angular momentum and the spin of the light beams.

PMID- 16599195
TI  - How thin can a microfiber be and still guide light?
AB  - For the adiabatically deformed optical fiber the intermode transmission
      amplitudes and loss vanish exponentially with the characteristic length of the
      fiber's nonuniformity. For this reason smoothly deformed optical fiber tapers can
      have very small losses. However, losses dramatically increase with a thinning of
      the microfiber down to a diameter much smaller than the radiation wavelength. The
      theory of nonadiabatic intermode transitions is briefly discussed and, by using
      this theory, the problem of the smallest diameter of a microfiber that can
      transmit evanescent radiation is studied. It is shown that even for an extremely
      high uniformity of microfiber the ability of light transmission does not leave
      much space for microfiber thinning: the propagating mode vanishes at a threshold
      value of the microfiber's diameter, that is smaller than the radiation wavelength
      by only an order of magnitude.

PMID- 16599196
TI  - Cross-phase modulation instability in photonic crystal fibers.
AB  - We report on the observation of cross-phase modulation instability in a highly
      nonlinear photonic crystal fiber. In such fibers the presence of higher orders of
      dispersion results in a complex phase-matching curve. We are able to observe this
      behavior experimentally and obtain excellent agreement between the measured and
      predicted shifts.

PMID- 16599197
TI  - Quasi-monochromatic fiber depolarizer and its application to polarization
      dependent loss measurement.
AB  - We theoretically derive the relationship between the degrees of polarization
      (DOPs) of input and output for an optical component with polarization-dependent
      loss (PDL) and birefringence. Based on the theoretical result, we propose a novel
      depolarizer for quasi-monochromatic light that can depolarize a fully polarized
      light with a 50 MHz linewidth to less than 0.2% in the DOP The depolarized light
      is then used to measure PDL in a single-mode optical fiber link. To the best of
      our knowledge, our new PDL measurement method is significantly faster than all
      known methods. Experimental results show excellent agreement with other methods.

PMID- 16599198
TI  - Effect of plastic strain energy density on polymer optical fiber power losses.
AB  - We explore the dependence of power losses on average plastic energy densities as
      rays propagate along deformed polymer optical fibers (POFs). The variation of
      power losses in deformed POFs with different bend radii and elongations are
      measured and analyzed. Three-dimensional elastic-plastic finite-element models
      are used to calculate average plastic energy densities in deformed POFs. The
      results indicate that the average plastic energy density introduced in a deformed
      POF can be considered a key index with which to study the power loss. Based on
      the experimental results, a curve-fitted equation is proposed for estimating the
      power loss by using the average plastic energy density for various bend radii.

PMID- 16599199
TI  - Observation of elliptical polarization rotation in a long twisted fiber.
AB  - The intensity-dependent polarization rotation caused by the self-induced
      nonlinear birefringence in a long twisted fiber is studied numerically and
      experimentally. By using a 1 km length of twisted fiber, we show that the effect
      of ellipse rotation accumulates monotonically as if the fiber were perfectly
      isotropic. Such behavior cannot be observed in a typical nontwisted fiber with
      randomly varying birefringence and is a unique feature of the twisted fiber, in
      which the large circular birefringence plays an essential role of preserving the
      handedness of elliptical polarization. We demonstrate a novel Faraday-mirror
      configuration to ensure automatic polarization alignment, which is directly
      applicable to achieving a simple and stable intensity discriminator.

PMID- 16599200
TI  - All-fused-silica miniature optical fiber tip pressure sensor.
AB  - An all-fused-silica pressure sensor fabricated directly onto a fiber tip of 125
      microm diameter is described. Simple fabrication steps include only cleaving and
      fusion splicing. Because no chemical processes are involved, the fabrication is
      easy, safe, and cost effective. Issues in sensor design and loss analysis are
      discussed. The sensor has been tested for static pressure response, showing a
      sensitivity of 2.2 nm/psi, a resolution of 0.01 psi (68.9 Pa), a hysteresis of
      0.025%, and capability of operation at temperatures up to 600 deegrees C. This
      miniature sensor may be suitable for medical diagnostics, environmental
      monitoring, and other industrial applications.

PMID- 16599201
TI  - Influence of transient phonon relaxation on the Brillouin loss spectrum of
      nanosecond pulses.
AB  - For pump-probe stimulated Brillouin scattering with a probe pulse of a few
      nanoseconds duration and with a finite DC level, the acoustic wave relaxation
      time varies with the pump power and the DC level. For a pump power of 1-6 mW, the
      acoustic wave relaxation changes from approximately 9 to 90 ns for polarization
      maintaining fiber at a temperature of -40 degrees C for a 2 ns pulse width. When
      the pulse DC ratio of the probe varies from 10 to 20 dB, the acoustic relaxation
      time changes from 24 to 45 ns for single-mode fiber at 25 degrees C. This induces
      a power-increment spectral feature in the detected AC pump signal in the
      Brillouin loss spectrum of two temperature or strain sections, where both
      spectral components appeared at positions far from those related to the natural
      phonon relaxation time (approximately 10 ns) equivalent length. The theoretical
      calculations confirm the prolonged phonon relaxation.

PMID- 16599202
TI  - Potential of two-photon-excited fluorescence for distributed fiber sensing.
AB  - The design and operating parameters of a new class of continuously distributed
      optical fiber sensor are described. By use of counterpropagating pulses, two
      photon excitation of fluorescence from ions doped into the fiber enables any
      position to be monitored. By this means temperature and also strain may be sensed
      with high spatial and temporal resolution. As the doped fiber is transparent for
      single-photon absorption at the wavelength of the light pulses, attenuation does
      not set an upper limit to its length.

PMID- 16599203
TI  - Lensed photonic crystal fiber obtained by use of an arc discharge.
AB  - A lensed photonic crystal fiber (PCF) is proposed as an effective element for an
      optical free-space interconnector. By simultaneously forming a beam-expansion
      region and a focusing lens on a single piece of PCF, effective coupling between
      PCFs could be achieved. A long working distance of up to 1 mm with wide
      longitudinal and lateral tolerances was measured. The optical characteristics of
      the lensed PCFs and the connectors made from them are analyzed experimentally and
      theoretically.

PMID- 16599204
TI  - Pixel resolution control in numerical reconstruction of digital holography.
AB  - A new method for resolution control in numerical reconstruction of digital
      holography is proposed. The wave field on a tilted or vertical plane can be
      reconstructed without being subject to the minimum object-to-hologram distance
      requirement, and the pixel resolution can be easily controlled by adjusting the
      position of a transitional plane. The proposed method solves the problem of pixel
      resolution control for small object-to-hologram distances and is especially
      useful for multicolor, multiwavelength digital holography and metrological
      applications. Experimental results are presented to verify the idea.

PMID- 16599205
TI  - Simultaneous diode-laser-based in situ measurement of liquid water content and
      oxygen mole fraction in dense water mist environments.
AB  - We performed what we believe are the first simultaneous in situ measurements of
      liquid water and oxygen concentrations in a dense water mist environment. Direct
      absorption tunable diode laser absorption spectroscopy was used to make oxygen
      concentrations and simultaneously quantify the liquid water via optical density
      measurements. This spectrometer with an absorption path length of only 36.8 cm
      was successfully tested during full-scale fire suppression tests with scattering
      losses up to 99.9%. The simultaneous oxygen and liquid water concentration
      measurements agree with fire suppression model calculations.

PMID- 16599206
TI  - Fourier transform ultraviolet-visible spectrometer based on a beam-folding
      technique.
AB  - A beam-folding technique in optical interferometry, where the number of beam
      folds used can be very large, is reported. This technique can be used as a low
      cost position-tracking method in a Fourier transform spectrometer (FTS) to cover
      the broad spectral range from UV to IR. The main advantage gained is the simple
      position-tracking algorithm used in sampling the interferogram. We have developed
      a UV-visible FTS, whose wavelength coverage is limited only by the optical
      elements (350 nm(-1) microm with off-the-shelf components). Preliminary results
      show that it can achieve a resolution of approximately 4 cm(-1) even with a ball
      bearing translation stage.

PMID- 16599207
TI  - Velocity imaging for the liquid-gas interface in the near field of an atomizing
      spray: proof of concept.
AB  - We describe adaptation of ballistic imaging for the liquid core of an atomizing
      spray. To describe unambiguously the forces that act to break apart the liquid
      core in a spray, one must directly measure the force vectors themselves. It would
      be invaluable, therefore, to obtain velocity and acceleration data at the liquid
      gas interface. We employ double-image ballistic imaging to extract velocity
      information through the application of image analysis algorithms. This method is
      shown to be effective for liquid phase droplet features within the resolution
      limit of the imaging system. In light of these results, it is clear that a three-
      or four-image implementation of this technique would allow the determination of
      acceleration, and by extension, information about the forces active in spray
      breakup.

PMID- 16599208
TI  - Simple and accurate measurement of the absorption coefficient of an absorbing
      plate by use of the Brewster angle.
AB  - We propose a simple and accurate method for measuring the refractive index and
      the absorption coefficient of an absorbing parallel plate. The method is
      essentially based on transmittance measurement with minimum reflectance at the
      Brewster angle for p-polarized light, which enables us to measure a low
      absorption loss of the order of 0.1 dB/cm for a typical plate thickness of 1 mm.
      The error that is due to the approximation used is practically negligible, and
      the accuracy of measured results depends mainly on the variations in the flatness
      and parallelism of the two surfaces of the sample and on instrumental errors.

PMID- 16599209
TI  - Random depth access full-field heterodyne low-coherence interferometry utilizing
      acousto-optic modulation and a complementary metaloxide semiconductor camera.
AB  - With analog scanning, time-domain low-coherence interferometry lacks precise
      depth information, and optical carrier generation demands a linear scanning
      speed. Full-field heterodyne low-coherence interferometry that uses a logarithmic
      complementary metal-oxide semiconductor camera, acousto-optic modulation, and
      digital depth stepping is reported, with which random regions of interest,
      lateral and axial, can be accessed. Furthermore, nanometer profilometry is
      possible through heterodyne phase retrieval of the interference signal. The
      approach demonstrates inexpensive yet high-precision functional machine vision
      offering true digital random access in three dimensions.

PMID- 16599210
TI  - Polymer saturable absorber materials in the 1.5 microm band using poly-methyl
      methacrylate and polystyrene with single-wall carbon nanotubes and their
      application to a femtosecond laser.
AB  - We report saturable absorber materials in the 1.5 microm band that consist of
      poly-methyl-methacrylate (PMMA) and polystyrene (PS) polymers with single-wall
      carbon nanotubes (SWNTs). A very uniform dispersion of SWNT in PMMA and PS
      polymers has been realized by using chlorobenzene or tetrahydrofuran as a
      dispersion solvent. These materials, which are as thick as 1 mm, are easily
      optically polished on both surfaces. This was difficult to achieve with previous
      thin-film materials. By incorporating PMMA/SWNT as a saturable absorber, a 171 fs
      pulse is successfully generated in a passively mode-locked fiber laser.

PMID- 16599211
TI  - Brillouin-Raman comb fiber laser with cooperative Rayleigh scattering in a linear
      cavity.
AB  - We demonstrate a multiple-wavelength Brillouin comb laser with cooperative
      Rayleigh scattering that uses Raman amplification in dispersion-compensating
      fiber. The laser resonator is a linear cavity formed by reflector at each end of
      the dispersion-compensating fiber to improve the reflectivity of the Brillouin
      Stokes comb. Multiple Brillouin Stokes generation has been improved in terms of
      optical signal-to-noise ratio and power-level fluctuation between neighboring
      channels. Furthermore, the linewidth of the Brillouin Stokes is uniform within
      the laser output bandwidth.

PMID- 16599212
TI  - Threshold reduction in a cyclic photonic molecule laser composed of identical
      microdisks with whispering-gallery modes.
AB  - Lasing modes in cyclic photonic molecules (CPMs) composed of several identical
      thin semiconductor microdisks in free space are studied in a linear
      approximation. Maxwell's equations with exact boundary conditions and the
      radiation condition at infinity are considered as a specific eigenvalue problem
      that enables one to find natural frequencies and threshold gains. It is
      demonstrated that careful tuning of the distance between the disks in CPMs is
      able to drastically reduce the lasing thresholds of the whispering-gallery modes
      having small azimuth indices.

PMID- 16599213
TI  - Oxyhemoglobin saturation measurements by green spectral shift.
AB  - From an analysis of new hemoglobin solution transmission spectra at various
      oxygen saturations (SO2), path lengths, and pH, we find the determination of SO2
      by using the classical oximetry technique to be poorly calibrated. We used this
      data set to develop a proposed method for SO2 determination based on the spectral
      shift of the hemoglobin transmission minimum between 475 and 510 nm. The method
      does not require accurate knowledge of hemoglobin extinction coefficients and is
      linear in relation to SO2 despite changes in path length, pH, or hemoglobin
      concentration.

PMID- 16599214
TI  - Real-time in vivo blood-flow imaging by moving-scatterer-sensitive spectral
      domain optical Doppler tomography.
AB  - We present a moving-scatterer-sensitive optical Doppler tomography (MSS-ODT)
      technique for in vivo blood flow imaging in real time by using a spectral-domain
      optical coherence tomography system. In MSS-ODT the influence of stationary
      scatterers is suppressed by subtracting adjacent complex axial scans before
      calculating the Doppler frequency shift. We demonstrate that MSS-ODT is a useful
      technique for accurate determination of blood vessel size by imaging flow in a
      small capillary tube with a 75 microm inner diameter. The flow profile obtained
      with MSS-ODT yields a substantially more accurate tube diameter than that
      obtained with the conventional phase-resolved method, which underestimates the
      diameter by about 23%. We also demonstrate that MSS-ODT provides improved
      sensitivity over the conventional phase-resolved method for imaging in vivo blood
      flow in small vessels in a mouse ear.

PMID- 16599215
TI  - Biomolecular imaging based on far-red fluorescent protein with a high two-photon
      excitation action cross section.
AB  - Received October 14, 2005; revised January 7, 2006; accepted January 9, 2006;
      posted January 12, 2006 (Doc. ID 65391) The two-photon excitation action cross
      section of Hc-Red fluorescent proteins (Hc-RFPs) is measured and found to be of
      the same order as that of enhanced green fluorescent proteins. With a 618 nm
      emission wavelength in the far-red region and with an excitation wavelength
      around 1200 nm, Hc-RPF-based two-photon fluorescence microscopy (2PFM) can offer
      deep penetration capability inside live samples and is ideal for in vivo gene
      expression study and biomolecular imaging in live objects. In vivo 2PFM of the
      developing heart deep inside a transgenic zebrafish embryo tagged by Hc-RFP is
      also successfully demonstrated.

PMID- 16599217
TI  - Noninvasive measurement of scattering anisotropy in turbid materials by nonnormal
      incident illumination.
AB  - Many existing methods for the recovery of optical parameters from turbid
      materials rely on the diffusion approximation, which does not permit the recovery
      of the degree of anisotropy in the scattering phase function. These methods also
      make the explicit assumption that light is normally incident at the top surface
      of the material. We demonstrate a steady-state imaging technique that uses
      nonnormally incident light to determine anisotropy parameter g by fitting Monte
      Carlo simulation results to high dynamic range images of the intensity profiles
      of samples. The proposed method is simpler than existing methods and does not
      rely on thin samples to produce reasonable results.

PMID- 16599216
TI  - Influence of the third-order parameter on diffuse reflectance at small source
      detector separations.
AB  - Spatially resolved reflectance close to source has received a great deal of
      attention recently. This research is considered to develop a new noninvasive
      technique for measuring the optical properties of biological media. Using Monte
      Carlo simulations, we investigated the influence of third-order parameter 5 on
      diffuse reflectance and found that the reflectance decreased with an increase of
      delta at a short source-detector separation of approximately 0.7-2 transport mean
      free paths. We show that the effects of two parameters, y and second-order
      parameter delta, on the reflectance are contrary. As a result the influence of
      the second-order parameter y on the reflectance is irregular when the condition
      delta delta<<delta gamma is not satisfied.

PMID- 16599218
TI  - Simulated annealing in ocular adaptive optics.
AB  - We present what is to our knowledge a first hardware realization of a simulated
      annealing algorithm in an adaptive optics system designed to image the retina of
      the human eye. The algorithm is applied to the retinal image itself without the
      need for wavefront sensors in the system. We find that this optimization
      algorithm can be an alternative to the traditional Hartmann-Shack sensing. We
      also compare the simulated annealing algorithm to the stochastic parallel
      gradient descent algorithm.

PMID- 16599219
TI  - Confocal reflectance theta line scanning microscope for imaging human skin in
      vivo.
AB  - A confocal reflectance theta line scanning microscope demonstrates imaging of
      nuclear and cellular detail in human epidermis in vivo. Experimentally measured
      line-spread functions determine the instrumental optical section thickness to be
      1.7 +/- 0.1 microm and the lateral resolution to be 1.0 +/- 0.1 microm. Within
      human dermis (through full-thickness epidermis), the measured section thickness
      is 9.2 +/- 1.7 microm and the lateral resolution is 1.7 +/- 0.1 microm. An
      illumination line is scanned directly in the pupil of the objective lens, and the
      backscattered descanned light is detected with a linear array, such that the
      theta line scanner consists of only seven optical components.

PMID- 16599220
TI  - Extended resolution wide-field optical imaging: objective-launched standing-wave
      total internal reflection fluorescence microscopy.
AB  - Standing-wave total-internal-reflection fluorescence (SW-TIRF) microscopy uses a
      super-diffraction-limited standing evanescent wave to extract the high-spatial
      frequency content of an object through a diffraction-limited optical imaging
      system. The effective point-spread function is better than a quarter of the
      emission wavelength. With a 1.45 numerical aperture objective and 532 nm
      excitation wavelength, a Rayleigh resolution of approximately 100 nm can be
      achieved, which is better than twice the resolution of conventional TIRF
      microscopy. This first experimental realization of SW-TIRF in an objective
      launched geometry demonstrates the potential for extended resolution imaging at
      high speed by using wide-field microscopy.

PMID- 16599221
TI  - Performance limits of delay lines based on optical amplifiers.
AB  - The performance of tunable buffers based on optical amplifiers and its
      improvement by use of gain flattening are analyzed. A simple analytical
      expression is obtained indicating that the gain required to attain tunable
      storage of N bits increases nonlinearly with N and reaches unrealistically high
      values for N>5. A comparison with other types of optical delay line is made.

PMID- 16599222
TI  - Transverse instabilities and pattern formation in two-beam-excited nonlinear
      optical interactions in liquids.
AB  - We describe observations of various transverse instabilities that occur when two
      laser beams intersect in nonlinear optical liquids. Patterns that we observe
      include two types of conical emission and the generation of a linear array of
      spots. These results can be understood in terms of the physical processes of self
      diffraction, two-beam-excited conical emission, and seeded modulational
      instability.

PMID- 16599223
TI  - Cross-phase-modulation nonlinearities and holographic solitons in periodically
      poled photovoltaic photorefractives.
AB  - We show that the nonlinearity in periodically poled photovoltaic photorefractives
      can be solely of the cross-phase-modulation type. The effects of self-phase
      modulation and asymmetric energy exchange, which exist in homogeneously poled
      photovoltaic photorefractives, can be considerably suppressed by the periodic
      poling. Finally, we demonstrate numerically that periodically poled photovoltaic
      photorefractives can support Thirring-type ("holographic") solitons, which to our
      knowledge have never been observed.

PMID- 16599224
TI  - Surface-emitted terahertz-wave generation by ridged periodically poled lithium
      niobate and enhancement by mixing of two terahertz waves.
AB  - Surface-emitted terahertz- (THz-) wave generation by difference-frequency mixing
      with ridge-shaped periodically poled lithium niobate (PPLN) was demonstrated. The
      PPLN had a ridge height of 300 microm, a thickness of 20 microm, and an
      interaction length of 35 mm. The ridge behaves as a slab waveguide for optical
      pump beams. The PPLN gives rise to THz waves in opposite directions,
      perpendicular to the pump-beam direction. Reflecting the THz wave on one side and
      overlapping it with the THz wave on the other side increased the total THz-wave
      intensity approximately 2.7 times compared with that without reflection and
      mixing.

PMID- 16599225
TI  - Simultaneous observation of CO isotopomer absorption by broadband difference
      frequency generation using a direct-bonded quasi-phase-matched LiNbO3 waveguide.
AB  - Rovibration absorption lines both of 12CO and 13CO are observed simultaneously
      with the output of a 2 microm broadband difference frequency generated in a
      direct-bonded quasi-phase-matched LiNbO3 waveguide, which is a 50 mm device with
      a single quasi-phase-matching period that is operated at a constant temperature.
      The wavelength conversion efficiency and the difference-frequency generation
      bandwidth reach 100%/W and 100 nm, respectively. The idler output bandwidth in
      the 2 microm region is obtained by group-velocity matching or phase-mismatch
      minimization when a 0.94 microm pump laser diode and a 1.55 microm tunable signal
      source are used.

PMID- 16599226
TI  - Trapping of discrete solitons by defects in nonlinear waveguide arrays.
AB  - We study the trapping process of moving discrete solitons by linear and nonlinear
      impurities embedded in a one-dimensional nonlinear cubic array. We show that
      there exist specific values for the strength of the impurity and for the angle
      where a strong trapping is obtained. We introduce a criterion for studying the
      scattering dynamics of localized waves in nonlinear extended systems where the
      trapping of energy takes place.

PMID- 16599227
TI  - Efficient generation of short terahertz pulses via stimulated Raman adiabatic
      passage.
AB  - We have analyzed the efficiency of coherent scattering of infrared radiation in
      molecular gases for the production of intense, short terahertz (THz) pulses by
      using stimulated Raman adiabatic passage for the preparation of coherence. We
      show that coherently driven molecular media potentially yield strong,
      controllable, short pulses of THz radiation. The pulses have energies ranging
      from several nanojoules to microjoules and time durations from several
      femtoseconds to nanoseconds at room temperature.

PMID- 16599228
TI  - Actively mode-locked optical parametric oscillator.
AB  - We report on what we believe to be the first demonstration of active mode locking
      of an optical parametric oscillator. An acousto-optic modulator is inserted into
      a nearly degenerate (approximately 1064 nm) and doubly resonant optical
      parametric oscillator based on periodically poled LiNbO3 and pumped with the
      second harmonic of a quasi-continuous-wave single-frequency Nd:YAG laser. When
      the modulation frequency is matched to the free spectral range of the cavity (120
      MHz), a pulsed regime is observed, with pulse durations as short as 700 ps.

PMID- 16599229
TI  - Single attosecond pulse generation in the multicycle-driver regime by adding a
      weak second-harmonic field.
AB  - We present a method of producing single attosecond pulses by high-harmonic
      generation with multicycle driver laser pulses. This can be achieved by tailoring
      the driving pulse so that attosecond pulses are produced only every full cycle of
      the oscillating laser field rather than every half-cycle. It is shown by
      classical and quantum-mechanical model calculations that even a minor addition
      (1%) of phase-locked second-harmonic light to the 800 nm fundamental driver pulse
      for high-harmonic generation leads to a major (15%) difference in the maximum
      kinetic energies of the recombining electrons in adjacent half-cycles.

PMID- 16599230
TI  - Terahertz wave generation and detection from a cdte crystal characterized by
      different excitation wavelengths.
AB  - Terahertz (THz) wave generation and detection from a (110)-oriented CdTe crystal
      via optical rectification and electro-optic sampling has been performed with
      laser wavelengths ranging from 710 to 970 nm. Three optical rectification regimes
      are studied with various excitation wavelengths: a resonance-enhanced regime
      above the bandgap, a highly phase-mismatched regime near the band gap, and a semi
      phase-matched regime. A CdTe crystal generates more THz power than a ZnTe crystal
      at 970 nm.

PMID- 16599231
TI  - Ultrafast noncollinear optical parametric chirped pulse amplification in
      KTiOAsO4.
AB  - Amplification of femtosecond pulses at 1.56 microm based on noncollinear
      parametric chirped pulse amplification in a potassium titanyl arsenate (KTA)
      crystal with pumping at 1.05 microm is reported. The 100 fs pulses of an erbium
      fiber laser are parametrically amplified while synchronously pumped by an
      amplified mode-locked Nd:YLF laser. This amplifier has a saturated gain of 65 dB
      with 30% conversion efficiency and has produced 160 fs pulses with peak powers of
      up to 0.75 GW. The system produced 380 mW before compression and can be readily
      scaled to the multiwatt range with bandwidths to support sub-100 fs pulses.

PMID- 16599232
TI  - Tomography of high harmonic generation in a cluster jet.
AB  - Tomographic measurement of high harmonic generation in a cluster jet was
      demonstrated by programming the cluster density distribution with a laser
      machining technique. The growth of harmonic energy with the propagation of the
      pump pulse was resolved by scanning the end of the argon cluster distribution in
      the path of the pump pulse. A downstream shift of the position of rapid growth
      and a decrease of the slope with increasing backing pressure as results of
      changes in the phase-matching condition were observed, which explains the
      presence of an optimal backing pressure.

PMID- 16599233
TI  - Design and fabrication of a double-axicon for generation of tailorable self
      imaged three-dimensional intensity voids.
AB  - We propose a new design for fabrication of a highly power-efficient double axicon
      to generate self-imaged three-dimensional intensity voids along the propagation
      of a beam. The conventional conical structure of an axicon is modified and shaped
      like an axiconlike structure with a double-gradient surface profile. The gradient
      conical surfaces generate Bessel beams with varying radial wave vectors that are
      superimposed and interfere to generate a sequence of three-dimensional intensity
      voids. The proposed element was fabricated using electron-beam lithography, and
      experimental verification of the design is reported.

PMID- 16599234
TI  - Space-domain lock-in amplifier based on a liquid-crystal spatial light modulator.
AB  - We present a two-dimensional (2D) spatial lock-in amplifier that provides a
      contrast ratio of more than 10,000:1 for transmitted and blocked intensity
      patterns using a conventional liquid-crystal spatial light modulator. The device
      is based on spatial-domain modulation-demodulation of intensity patterns under
      coherent imaging conditions. The operation of the 2D lock-in amplifier is
      illustrated by implementing Young's double-slit arrangement for measurements of
      the mutual coherence between individual emitters of a 2D phase-coupled array of
      vertical cavity surface emitting lasers.

PMID- 16599235
TI  - Self-activated liquid-crystal cells with photovoltaic substrates.
AB  - We show that photovoltaic fields are capable of efficiently reorienting liquid
      crystals, leading to new concepts of optically addressable light modulators.
      Using an arrangement consisting of a liquid-crystal layer between LiNbO3:Fe
      photovoltaic substrates, we observed spatial filtering due to self-phase
      modulation in a planar-oriented cell and nonlinear transmission between crossed
      polarizers in a twist-oriented cell. These processes do not require an external
      electric field. The substrates are arranged such that light propagates along the
      +c axis in each substrate, allowing a secondary process of power transfer to
      occur through contradirectional photorefractive two-beam coupling.

PMID- 16599236
TI  - Bistable polarization switching in mutually coupled vertical-cavity surface
      emitting lasers.
AB  - We theoretically investigate the polarization-resolved dynamics of two vertical
      cavity surface-emitting semiconductor lasers that are mutually coupled through
      coherent optical injection. We find a sequence of bistable polarization
      switchings that can be induced by changing either the coupling strength or the
      optical propagation phase. The successive polarization switchings are correlated
      with the creation of new compoundcavity modes when these parameters are
      continuously varied.

PMID- 16599237
TI  - Blue five-level frequency-upconversion system in rubidium.
AB  - We demonstrate production of continuous coherent blue laser light by using a five
      level system in rubidium vapor. Two low-power lasers, at 780 and 776 nm, induce
      strong atomic coherence in the 5S-5P-5D states. The atoms decay to the 6P excited
      state, from which stimulated emission produces a coherent blue (420 nm) beam. We
      have coupled both ground-state hyperfine levels, effecting coherence between four
      levels. The coherent blue output is enhanced by several mechanisms, including
      stronger coupling to a larger fraction of the atomic population, operation at a
      detuning such that the vapor is nominally transparent to the 780 nm pump field,
      reduced losses owing to optical pumping, and optimal phase matching. We report
      experimental findings and compare them with results from a semiclassical Maxwell
      Bloch model.

PMID- 16599238
TI  - Simultaneous application of single-shot Ramanography and particle image
      velocimetry.
AB  - A simultaneous two-dimensional determination of the concentration field and the
      velocity field in a turbulent mixing process is demonstrated for the first time
      to the best of our knowledge by using planar Raman scattering (Ramanography) and
      particle image velocimetry. An example of application of these techniques is
      tested by considering the mixing characteristic of a two-component nozzle for the
      injection of liquid ethanol into pure water.

PMID- 16599239
TI  - Simplified spectral phase interferometry for direct electric-field reconstruction
      by using a thick nonlinear crystal.
AB  - We propose and demonstrate a novel implementation of spectral-shearing
      interferometry (SSI) for reconstructing the electric field of ultrashort pulses
      by utilizing asymmetric group velocity matching in a long nonlinear crystal. The
      proposed configuration eliminates the requirement for a linearly chirped
      auxiliary pulse that is in common in all existing SSI methods, relying on
      nonlinear conversion to produce a spectral shear.

PMID- 16599240
TI  - Octave-spanning Ti:sapphire laser with a repetition rate >1 ghz for optical
      frequency measurements and comparisons.
AB  - We demonstrate a self-referenced, octave-spanning, mode-locked Ti:sapphire laser
      with a scalable repetition rate (550 MHz - 1.35 GHz). We use the frequency comb
      output of the laser, without additional broadening in optical fiber, for
      simultaneous measurements against atomic optical standards at 534, 578, 563, and
      657 nm and to stabilize the laser offset frequency.

PMID- 16599241
TI  - Platelet function in anaphylaxis.
AB  - Human platelets, following immunological or nonimmunological activation, are
      capable of releasing a variety of biologically active mediators and are able to
      actively participate in hypersensitivity reactions, including anaphylaxis. These
      cells constitutively express functional receptors for the Fc fragment of IgE,
      both the low affinity receptor (Fc epsilonRII) and the high affinity receptor (Fc
      epsilonRI), and could be activated via IgE. Alterations in platelet function have
      been demonstrated in patients with allergy and nonallergic hypersensitivity,
      including hypersensitivity to acetylsalicylic acid. Moreover, activated platelets
      may be responsible for anaphylactic transfusion reactions. Various haemostatic
      disturbances, particularly a drop in platelet number, were observed during
      anaphylactic shock. The current review summarises the data from human and
      experimental studies on platelet function in anaphylactic reactions.

PMID- 16599242
TI  - In vitro basophil activation using CD63 expression in patients with bee and wasp
      venom allergy.
AB  - The diagnosis of insect venom allergy and the indication for specific
      immunotherapy is based on history, skin tests and demonstration of hymenoptera
      venom-specific IgE-antibodies. Cellular tests can add useful information but the
      role of basophil activation tests for the different venoms has to be elucidated
      further. We evaluated positive reactions in a basophil activation test using CD63
      expression as marker independently for bee or wasp venom in patients with
      hymenoptera allergy. Fifty-seven patients with a history of insect venom
      anaphylaxis were examined (12 x bee venom, 39 x wasp venom, 6 x bee plus wasp
      venom). Skin tests and determination of specific IgE-antibodies were performed.
      Basophil activation test (BAT) using CD63 expression was performed after
      stimulation with different concentrations of bee and wasp venom. The BAT is based
      on double staining with anti-IgE antibodies and anti-CD63 and subsequent
      determination of the percentage of activated basophils by flow cytometry. In
      patients with bee venom allergy, BAT was positive in 100% to bee venom and 75% to
      wasp venom. In patients with bee and wasp venom allergy, positive reactions for
      both venoms were found in 100%. In patients with wasp venom allergy, 97% reacted
      positive to wasp venom and only 56% to bee venom. These results show the
      reliability of the basophil activation test as a cellular test in the in vitro
      diagnosis in patients with bee and wasp venom allergy. They also show that
      positive reactions in the basophil activation test reflect both sensitization
      status and cross-reactivity between venom species.

PMID- 16599243
TI  - Children's asthma and the third world: an approach.
AB  - BACKGROUND: More than a million visits/year characterize acute asthma morbidity
      at Venezuela's (24 million inhabitants) Ministry of Health ambulatory services,
      caring for 80% or more of the population; acute morbidity from asthma is second
      to "viral syndrome" but ahead of diarrhea and other diseases. These acute
      episodes are the only contact of a poor asthmatic child with this health care
      system and portray the prevailing approach focused around acute care: to be
      reversed, a simple cost/effective program ought to be implemented during these
      acute asthma visits. Since convenience of administration is a key factor in
      compliance, a pilot study to explore the efficacy of budesonide CFC 400 microg
      administered on a once-a-day basis for adherence was carried out within a
      naturalistic real-world design. METHODS: Thirty persistent asthmatic patients
      attending the Allergology Unit of the Hospital Pediatrico San Juan de Dios in
      Caracas were enrolled, and their asthma signs/symptoms quantified and registered
      on diary cards (0-3 scale) as well as peak flow measurements in am/pm for a
      period of 2 weeks prior to budesonide administration (control data) and until
      completion of study. Only 12 (mean age: 9 years) of the initial patients were
      able to properly keep a diary and scheduled visits for a period of 15 weeks.
      RESULTS: Data allowed comparison between pre- and post-treatment symptoms/signs
      scores and PF values. After 3 weeks treatment with budesonide, statistically
      significant improvements were shown for all parameters, except for PF, whose
      minor improvements did not reach statistical significance. CONCLUSIONS:
      Budesonide CFC 400 microg administered once a day seems effective in control of
      asthma signs/symptoms within study design. Confirmation of the above findings in
      larger groups of patients, treated similarly and for longer periods of time,
      seems justified. A simple cost-effective intervention, analogous conceptually to
      the proven successful oral rehydration therapies for diarrhea in public health,
      should be considered in third world countries with high urban asthma prevalence.

PMID- 16599244
TI  - Bronchial hyperresponsiveness is a common feature in patients with chronic
      urticaria.
AB  - BACKGROUND: Chronic urticaria (CU) is a skin disorder characterized by long
      lasting release of histamine, and sometimes leukotrienes, from both mast cells
      and basophils. Although both these substances are potent inductors of contraction
      of airway smooth muscle, pulmonary function and airway hyperresponsiveness have
      not been systematically investigated in patients with CU. OBJECTIVE: To assess
      pulmonary function and airway hyperresponsiveness in patients with CU. METHODS:
      Twenty-six clinically well-characterized adult patients with CU (M/F 8/18; mean
      age 47 years) underwent pulmonary function tests and methacholine provocation
      during a phase of moderate activity of their disease. Twenty-six adult asthmatic
      patients submitted to methacholine provocation were used as controls. RESULTS:
      Two patients (8%) had overt asthma on baseline pulmonary function tests. Twenty
      (77%) patients with a normal baseline pulmonary function showed significant
      bronchial hyperresponsiveness on methacholine provocation. Altogether, 22/26
      (85%) patients had asthma or abnormal bronchial reactivity. Airway
      hyperresponsiveness was not associated with gender, disease duration, intolerance
      to NSAID, positive autologous serum skin test or respiratory allergy. On average,
      asthmatic controls showed a much severer airway hyperresponsiveness than
      urticaria patients (p < 0.01). CONCLUSION: Patients with CU frequently show
      bronchial hyperresponsiveness. Prospective studies are needed to assess whether
      they are at risk for bronchial asthma.

PMID- 16599245
TI  - Aerobiological and allergenic analysis of cupressaceae pollen in Granada
      (Southern Spain).
AB  - Cupressaceae pollen has been cited in recent years as one of the major airborne
      allergens of the Mediterranean region, prompting us to conduct an exhaustive
      analysis on the aerobiological behaviour of this pollen in the Iberian Peninsula
      and the repercussion that it has had on the atopic population. The aerobiological
      study, performed from 1996 to 2003 in the city of Granada (S. Spain), used a
      volumetric Hirst collector. The results indicate that this pollen is present in
      the air most of the year, registering a high incidence during the winter months.
      This type of pollen behaved irregularly in the air, fluctuating yearly,
      seasonally, and within the same day. Temperature and humidity were the parameters
      that most directly influence the variability of this allergen, while rainfall
      prior to flowering increased pollen production. The predictive models used
      estimated a high percentage of the levels reached over the short term by this
      pollen in the atmosphere of Granada. The clinical study performed with atopic
      patients showed that some 30% of the population with pollinosis are sensitive to
      Cupressaceae pollen, affecting people of both genders equally. On the other hand,
      the most sensitive age group was 21-40 years of age, while children and the
      elderly registered almost negligible values. Most of the sensitive subjects
      resided within the city or in the metropolitan area, where environmental
      pollution reached high levels, while the pathology was found to be less frequent
      in rural zones. The most frequent symptoms were upper-respiratory ailments and an
      asthmatic profile.

PMID- 16599247
TI  - Differences in the spatial distribution of airborne pollen concentrations at
      different urban locations within a city.
AB  - BACKGROUND: The objective of the present work was to compare pollen counts at
      three different urban locations within a city to each other and to the counts
      from a fixed trap. This information could be useful to delimit zones in the
      urbanized part of the city according to the risk of allergic affections. METHODS:
      Aerobiological sampling using portable traps was carried out at three points in
      urban zones of the city of Badajoz (SW Spain) over one year at the same time as
      continuous sampling using a fixed trap at a point in the nonurban outskirts of
      the city. The sources of airborne pollen were studied by counting the trees in
      the streets and squares of the selected zones. A statistical analysis was
      performed of the differences between the portable and fixed traps and of the
      temporal and spatial variation in the city as a function of the distribution of
      the most important pollen sources. RESULTS: Forty-eight pollen types were
      identified with the fixed trap, and 28 with the portable traps. The grass, olive,
      and oak pollens come from almost exclusively external sources, there being no
      spatial differences in their concentrations in the city. Cypress pollen
      concentrations were much higher at the urban locations than at the fixed trap
      site. Plane tree pollen levels could be locally very high, reflecting the
      proximity of the source. Except for ornamental plants, pollen levels were lower
      at the urban locations than at the site on the outskirts of the city.
      CONCLUSIONS: (1) Using portable traps at different urban zones in a city could
      provide information about the spatial variation of atmospheric pollen levels. (2)
      A knowledge of the often widely variable distribution of ornamental plants with
      potentially allergenic pollen could be useful in indicating city zones with a
      greater or lesser incidence of potential pollinosis.

PMID- 16599246
TI  - Taxis but not private cars are mite allergen reservoirs in Brazil.
AB  - Indoor allergens are major causative agents in allergic disease development.
      Besides homes, public transport vehicles have been considered important mite and
      pet allergen reservoirs. Our recent studies on allergen exposure in automobiles
      showed that different allergen levels are found in private cars versus taxis. We
      quantified group 1 Dermatophagoides spp. (Der 1), Felis domesticus (Fel d 1), and
      Canis familiaris (Can f 1) allergen levels by ELISA in dust samples from 60 taxi
      and 60 private car upholstered seats. Mean levels of Der 1 and Fel d 1 were
      significantly higher in taxis than private cars. A significantly higher
      percentage of taxis (42%) harboring sensitizing levels of Der 1 compared to
      private cars (5%) was also found. In spite of the low mean Fel d 1 levels,
      comparison of the percentage of vehicles with moderate Fel d 1 levels showed a
      significant difference between taxis and private cars (43% vs. 20%). On the other
      hand, mean Can f 1 levels were significantly higher in private cars compared to
      taxis concomitant with a significantly higher percentage of private cars
      containing moderate Can f 1 levels than taxis (53% vs. 28%). We conclude that
      upholstered seats from Brazilian taxis but not private cars constitute an
      important mite allergen reservoir. Thus, additional effective measures for the
      reduction of allergen exposure in vehicles within the global allergen avoidance
      strategy should also be routinely accomplished to minimize the induction of
      sensitization and symptoms in allergic patients.

PMID- 16599248
TI  - Differences between asthma and COPD in the elderly.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are both characterized by
      the presence of airflow obstruction. Both diseases are not rare in the elderly
      population. Distinguishing between these diseases is difficult and may be
      impossible in some older patients. The aim of the study was to investigate
      clinical and functional characteristics and the presence of atopic status in
      elderly subjects compared to COPD patients. Fifty-one patients over 60 years of
      age were selected for the study (27 patients with late-onset asthma, 24 patients
      with COPD). Atopy was defined by skin prick test and serum total IgE
      concentrations which were measured in all patients. Pulmonary function tests
      including airflow rates, lung volumes, airway resistance, diffusing capacity, and
      arterial blood gases analysis were performed in all patients. The rate of skin
      prick test positivity in asthmatics was significantly higher than that of the
      COPD patients. FEV1 was lower in COPD patients than in asthmatic patients.
      Bronchial reversibility in asthmatics became significantly higher than in COPD
      patients. While FRC and RV were increased in both groups showing same degree of
      pulmonary hyperinflation, patients with COPD demonstrated significantly decreased
      DLCO when compared to asthmatic patients. The level of both PO2 and PCO2 in
      patients with COPD significantly differed from asthmatics. In conclusion, a
      history of heavy smoking, decreased diffusing capacity for carbon monoxide, the
      presence of more prominent lung hyperinflation and chronic hypoxemia favour the
      diagnosis of COPD, whereas atopy and significant bronchodilator responsiveness
      favour the diagnosis of asthma.

PMID- 16599249
TI  - Immediate hypersensitivity to corticosteroids.
AB  - INTRODUCTION: In comparison with the extremely frequent use of corticosteroids in
      different diseases, immediate allergic reactions remain uncommon. In addition to
      the steroid molecule, the causative agent of these reactions can be an excipient.
      MATERIAL AND METHODS: We report seven cases of immediate reactions induced by
      different preparations of corticosteroids. Skin tests with the suspected steroid
      and excipients were carried out. In patients with negative skin tests, oral or
      parenteral challenges were performed with the drug and the excipients involved.
      Challenge tests with at least two other corticosteroids belonging to another or
      even the same group of the Coopman classification were carried out. RESULTS: Of
      the 7 patients, six had positive skin tests with the suspected preparation of
      corticoid: three cases with methylprednisolone acetate, two cases with
      carboxymethylcellulose and one case with the complete triamcinolone preparation.
      Only in one case did we have to challenge with the suspected steroid preparation
      to confirm the diagnosis. All challenge tests with other corticosteroids
      belonging to another or to the same group of the Coopman classification were
      negative. CONCLUSIONS: The reactions were caused by the steroid molecule
      (Triamcinolone or methylprednisolone succinate) in four patients, by an excipient
      (carboxymethylcellulose) in another two patients and we could not identify the
      sensitized molecule in one patient. We did not demonstrate cross-reactivity
      between different corticosteroids.

PMID- 16599250
TI  - Rofecoxib, as a safe alternative for acetyl salicylic acid/nonsteroidal anti
      inflammatory drug-intolerant patients.
AB  - BACKGROUND: Intolerance to acetylsalicylic acid (ASA) and nonsteroidal anti
      inflammatory drugs (NSAIDs) is a crucial problem in medical practice. There is
      therefore a need for safer NSAIDs in analgesic-intolerant patients. OBJECTIVE: To
      assess the safety of rofecoxib, a selective COX-2 inhibitor, in ASA/NSAID
      intolerant patients. METHODS: A single blind, placebo-controlled oral challenge
      procedure was applied to 94 adult patients (M/F: 30/64, mean age: 39.2 +/- 11.9
      yrs) with a reliable history of ASA/NSAID intolerance. 1/4 and 3/4 divided doses
      of placebo and rofecoxib were given with 2-hour intervals on consecutive days.
      During the challenge procedure, blood pressure, heart rate, nasoocular, pulmonary
      and cutaneous symptoms were monitored. Erythema, pruritus accompanied by
      erythema, urticaria/angioedema, rhinorrea, nasal obstruction, sneezing, dyspnea
      or cough associated with a decrease of at least 20% in the FEV1, and hypotension
      were considered as positive reactions. RESULTS: None of the patients reacted to
      placebo. Only one patient (1.1%) presented urticarial-type cutaneous reaction to
      rofecoxib challenge. The remaining patients (98.9%) perfectly tolerated the drug
      challenge. CONCLUSION: Rofecoxib can be used as a safe alternative drug for
      ASA/NSAID intolerant patients.

PMID- 16599251
TI  - Allergy to chironomid larvae (red migde larvae) in non professional handlers of
      fish food.
AB  - Chironomids are insects which inhabit wetlands. In countries such as Sudan, The
      United States. Egypt and Japan they are the cause of serious environmental
      allergy. In Europe, and particularly in Spain, allergy to Chironomids is
      infrequent and has only been described in patients who handle Chironomid larvae
      which form part of certain fish foods. MATERIALS AND METHODS: We report a case of
      hypersensitivity to the Chironomid Midge (Chironomus thummi thummi) in a 23-year
      old patient who on two occasions, after being in contact with fishfood, suffered
      rash, rhinoconjunctivitis, dyspnea and dysphagia. A Prick test was carried out
      with the habitual pneumoallergens, Chironomid Midge extract (PBS: 1.3 mg/ml),
      Common Mosquito (Culex pipiens), Squid, Mussel, Prawn and Anisakis. Conjunctival
      provocation was also carried out with Chironomid Midge extract; detection of
      specific IgE for Chironomid Midge, Common Mosquito (Aedes comunis), Mussel,
      Squid, Shrimp, Anisakis, house dust and house mites by means of the CAP
      technique; detection of IgE by means of ELISA in response to Chironomid Midge,
      Aedes mosquito, Squid, Prawn, Mussel and Anisakis; ELISA-inhibition and
      Immunoblott-inhibition. RESULTS: The positive results of the cutaneous tests, the
      detection of specific IgE and conjunctival provocation confirmed the existence of
      an IgE-mediated mechanism. In our patient, the in vitro techniques demonstrated
      cross reactivity with the Common Mosquito. CONCLUSIONS: We report on a patient
      with a case history of rhinoconjunctivitis, rash, dyspnea, and dysphagia after
      handling fish food. The etiological agent was the Chironomid larvae. The
      sensitization of our patient has been demonstrated by means of in vivo and in
      vitro techniques.

PMID- 16599252
TI  - Adverse reaction in a patient with aspirin-induced asthma treated with
      zafirlukast.
AB  - Asthmatic patients receiving antileukotrienes may develop hypereosinophilia as a
      part of a Churg-Strauss syndrome. It is unclear if this effect is directly
      related to the administration of antileukotrienes or a consequence of the
      corticosteroid-sparing effect of antileukotrienes unmasking a Churg-Strauss
      syndrome. We present a case of hypereosinophilia related to zafirlukast therapy.
      The patient did not fulfil criteria for Churg-Strauss syndrome. Symptoms and
      laboratory findings improved after zafirlukast was removed.

PMID- 16599253
TI  - Food-dependent exercise-induced anaphylaxis to pistachio.
AB  - We report the case of a 16-year-old male who, 30 minutes after beginning to play
      football with previous ingestion of pistachio nuts, experienced an anaphylactic
      reaction. Prick-by-prick test with roasted pistachios was negative. Specific IgE
      antibodies to pistachio, cashew nuts and mango were negative. An open oral
      challenge test with pistachio in resting conditions was negative. Treadmill
      ergonometric stress in a fasting state and 60 minutes after a meal without
      pistachio gave negative results. A specific food exercise challenge 60 minutes
      after ingestion of 50 g pistachio nuts was positive, showing mild diffuse
      erythema and small wheals in face and thorax. To the best of our knowledge, this
      is the first described case of specific food dependent exercise-induced
      anaphylaxis to pistachio. Negative allergologic tests is an unusual condition,
      since most cases appear to be IgE-mediated. In this case, a positive specific
      food exercise challenge test provided a definite diagnosis.

PMID- 16599254
TI  - Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel
      openers as a possible medical treatment of the overactive bladder and urge
      incontinence.
AB  - Urinary incontinence affects millions of people worldwide and also represents a
      social problem. People of all ages suffer from urinary incontinence. The disease
      is found in about 30% of women aged 30 to 60 years. There are different types of
      incontinence. Urge incontinence is the most often pharmacologically treated type.
      The mainly used substances belong to the class of antimuscarinic drugs. Their use
      is limited by several side effects. Furthermore, in some patients anticholinergic
      medication is ineffective and antimuscarinics used as single medication do not
      lead to a sufficient therapeutic effect. Other possible pharmacological
      substances for treatment of overactive bladder (detrusor instability) associated
      with urge and urge incontinence are the selective beta-adrenoceptor-agonists
      which are mainly responsible for the adrenergic mediated relaxation. It depends
      on the species, which beta-adrenoceptor-subtype (the beta2- and/or beta3
      adrenoceptor) mainly mediates the relaxation. Non selective beta-adrenoceptor
      agonists exhibit serious cardiovascular side effects like tachycardia or decrease
      of blood pressure by stimulating beta1- and beta2-adrenoceptors. These side
      effects should be decreased when using selective agonists. Additionally,
      substances whose targets are membrane channels of muscle cells could be
      interesting for treatment of overactive bladder. This group includes L-type
      calcium antagonists and potassium channel openers of ATP-sensitive potassium
      channels or BK channels. Especially the local use of the pharmacologically very
      potent calcium antagonists could be an interesting therapeutic approach, since
      systemic cardiovascular side effects were avoided. After chronic oral treatment
      with different calcium antagonists effects on the detrusor muscle were reduced or
      could not be detected, possibly due to an upregulation of 1,4-dihydropyridine
      sensitive potassium channels. A very interesting approach is the use of potassium
      channel openers said to be selective for the urinary bladder. If there is a
      selectivity for the detrusor muscle, cardiovascular side effects were reduced.
      Possibly, the local use is a useful application form. Selective beta-adrenoceptor
      agonists, calcium antagonists and potassium channel openers are pharmacological
      approaches, which are not yet available for clinical use.

PMID- 16599255
TI  - Multiple enzyme inhibitions by histamine H3 receptor antagonists as potential
      procognitive agents.
AB  - Novel highly affine histamine H3 receptor ligands with additional inhibitory
      effects on the main histamine metabolizing enzyme in the brain, N
      methyltransferase, chemically show structural elements of the
      acetylcholinesterase inhibitor tacrine. H3 receptor antagonism, inhibition of
      metabolisation of neuronal histamine as well as inhibition of hydrolysis of
      acetylcholine are each one believed to improve reduced cognitive functions, which
      is useful for symptomatic treatment of Alzheimer's disease. Some of the new
      compounds proved in a slightly modified colorimetric Ellmann's assay to be potent
      inhibitors of acetylcholinesterase and of butyrylcholinesterase which is another
      catalytic enzyme hydrolysing acetylcholine. Some compounds with (sub)nanomolar
      activities on the histamine-related targets are also active in the nanomolar
      concentration range on both cholinesterase targets being 5- to 40-times more
      potent than tacrine. Preliminary structure-activity relationships could already
      be drawn from the small number of compounds. The compounds acting as hybrid drugs
      simultaneously on four different targets to enhance cognitive functions via
      different pathways are promising lead structures for a new approach in the
      treatment of Alzheimer's disease.

PMID- 16599257
TI  - NMR regulatory analysis: enantiomeric purity determination for (R)-(-)
      desoxyephedrine and antipode methamphetamine.
AB  - Regulatory enantiomeric purity direct determination for (S)-(+)-methamphetamine,
      the widely abused DEA schedule II controlled substance, and (R)-(-)
      desoxyephedrine, over-the-counter nasal inhaler decongestant were developed using
      400 MHz 1H NMR spectroscopy. The efficient enantiomeric differentiation was
      obtained using a diamagnetic chiral solvating agent to dissimilarly perturb the
      NMR spectra of the enantiomeric solutes. Nonequivalence behavior was studied in
      terms of all variables that affect population and intrinsic spectra of the fast
      diastereomeric solvates. Assignment of enantiomer configuration was based on the
      relative field position of the resolved enantiomeric signals. Optimization of
      experimental conditions provided significant resolved enantiomeric signals
      suitable for quantification. Utilizing the relative intensities of the
      corresponding enantiomeric signals of the N-CH3 assigned to (S)-(+)
      methamphetamine and (R)-(-)-desoxyephedrine, the analysis of synthetic
      enantiomeric mixtures by the proposed methods demonstrated excellent agreements
      with the known values of the enantiomers present. The mean +/- SD recovery values
      for the (R)-(-)-enantiomer was 99.9 +/- 0.4% of added antipode (n = 7). The
      optically pure enantiomer was used to establish the minimum amount detected by
      the proposed NMR spectroscopic method.

PMID- 16599256
TI  - [Contribution to the erythroquine and thalleioquine reaction].
AB  - The 8,8'-biquinoline-5,5'-diones 2A are formed by the erythroquine and
      thalleioquine reaction from the 6-methoxyquinolines 1 as model compounds. The red
      substances 2A react with hydrochloric acid to yield the yellow
      biquinolinedihydrochlorides 3. The structure of 3b dihydrate is determined by X
      ray crystal analysis. The redox properties of 2A are investigated by voltammetric
      methods.

PMID- 16599258
TI  - Novel self-aggregates of chitosan oligosaccharide grafted stearic acid:
      preparation, characterization and protein association.
AB  - A novel hydrophobically modified chitosan oligosaccharide (CSO) containing 5.4
      stearic acid (SA) groups per 100 anhydroglucose units was synthesized by an 1
      ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)-mediated coupling reaction.
      The purified copolymer was structurally characterized by IR spectroscopy.
      Characteristics of self-aggregates of the amphiphilic copolymers were studied by
      fluorescence spectroscopy and dynamic light scattering. The critical aggregation
      concentration (cac) value of the self-aggregates in aqueous solution was
      determined by measuring the fluorescence intensity of pyrene as a fluorescent
      probe. Mean diameter of self-aggregates in pH 7.0 PBS was 25.0 +/- 14.7 nm with a
      unimodal size distribution. The diameter, as well as the zeta potential of self
      aggregates increased when the pH value of dispersion medium decreased. Bovine
      serum albumin (BSA) was further enveloped in the interface of different single
      self-aggregate and formed nanoparticles. The size of BSA-loaded stearic acid
      modified CSO nanoparticles depended on the pH values of the dispersed aqueous
      vehicle, and the size diminished when the pH values of the dispersed aqueous
      vehicle decreased, whilst, the BSA encapsulation efficiency enhanced. The
      nanoparticles were characterized by Transmission Electron Microscopy (TEM). BSA
      release from stearic acid modified CSO nanoparticles decreased when the pH values
      of the delivery media decreased, in the range from 7.2 to 5.8.

PMID- 16599259
TI  - Sustained release of bee venom peptide from biodegradable thermosensitive PLGA
      PEG-PLGA triblock copolymer-based hydrogels in vitro.
AB  - Biodegradable thermosensitive poly (DL-lactide-co-glycolide-b-ethylene glycol-b
      DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers with DL
      lactide/glycolide molar ratio ranging from 6/1 to 15/1 were synthesized from
      monomers of DL-lactide, glycolide and polyethylene glycol and were evaluated for
      sustained release of bee venom peptide in vitro. The resulting copolymers are
      soluble in water to form free flowing fluid at room temperature but become
      hydrogels at body temperature. The gelation temperature of the copolymer
      solutions can be influenced by the concentration and DL-lactide/glycolide molar
      ratio of the copolymers. The release of bee venom peptide from the copolymer
      based hydrogel and hydrogel degradation in the phosphate buffer (pH 7.4) was
      studied at 37 degrees C under agitation. Bee venom peptide was released from the
      copolymer-based hydrogels over 40 days in vitro and the variation of DL
      lactide/glycolide molar ratio in the PLGA block of the copolymer did not
      significantly affect the release rate of bee venom peptide (P > 0.05). The
      hydrogels undergo slower degradation and then faster degradation rate during the
      whole release stage. Accordingly, the mechanism of bee venom peptide was Fickian
      diffusion during initial stage and then may be a combination of diffusion and
      degradation. The synthesized copolymers have the advantage of gelation
      temperature over the ReGel system. These results indicate that the PLGA-PEG-PLGA
      copolymer-based hydrogel could be a promising platform for sustained delivery of
      bee venom peptide.

PMID- 16599260
TI  - Development and in vitro/in vivo evaluations of bioadhesive buccal tablets for
      nicotine replacement therapy.
AB  - Buccal bioadhesive tablet formulations of nicotine hydrogen tartrate (NHT) for
      nicotine replacement therapy (NRT) were developed using chitosan and carbomer at
      different ratios. Magnesium hydroxide was incorporated into the formulations as
      pH increasing agent. In vitro release and bioadhesion properties of the tablets
      were investigated. Release of NHT from the tablets was increased with the
      increasing amount of chitosan in formulations whilst the bioadhesion of the
      tablet was decreased. In vivo studies were carried out in healthy, non-smoker
      volunteers in comparison to a commercially available transdermal patch. Plasma
      nicotine and cotinine levels were determined using gas chromatography-mass
      spectrophotometry. No significant difference was found between the maximum plasma
      nicotine concentrations (Cmax) obtained with the buccal tablet and the
      transdermal patch (p > 0.05). Time to reach the Cmax was 2.9 +/- 0.2 h and 11.5
      +/- 1.3 h, and AUC0-24 values were 59.3 +/- 5.1 ng x h x mL(-1) (0-12 h) and
      204.1 +/- 31.2 ng x h x mL(-1) for buccal tablet and transdermal patch,
      respectively.

PMID- 16599261
TI  - Preparation and characterization of EP-liposomes and Span 40-niosomes.
AB  - Clotrimazole, an imidazole derivative antifungal agent, has been widely used for
      the treatment of mycotic infections of the genitourinary tract. In order to
      develop alternative formulations for the vaginal administration of clotrimazole
      which would provide sustained and controlled release of the appropriate drug for
      local vaginal therapy, liposomes/niosomes were evaluated as delivery vehicles. To
      optimize the preparation of the liposomes/niosomes with regard to size and
      entrapment efficiency, multilamellar liposomes/ niosomes containing the drug were
      prepared by a lipid hydration method. The liposomes/niosomes thus prepared were
      evaluated for their stability as drug-loaded liposomes/niosomes in simulated
      vaginal fluid at 37 +/- 1 degrees C. The two vesicle systems were also evaluated
      with regard to rat and rabbit vaginal irritation.

PMID- 16599262
TI  - Compression behavior of formulations from Phyllanthus niruri spray dried extract.
AB  - The aim of this study was to evaluate the compression behavior of Phyllanthus
      niruri spray dried extract as well as the influence of excipients on the
      properties of tablets containing a high dose (70% by weight) of this product. The
      effect of excipients was studied by a 22 factorial design. The factors
      investigated were the type of disintegrant (croscarmellose sodium and sodium
      starch glycolate) and the type of filler/binder (microcrystalline cellulose and
      dibasic dicalcium phosphate). The tablets were produced on a single punch tablet
      press using a constant compression force of 5000 N. The tablets formulated with
      microcrystalline cellulose presented a plastic behavior while the tablets
      containing dibasic dicalcium phosphate disclosed a fragmentary behavior. The
      disintegration time was significantly influenced by both factors, however, the
      tensile strength was only affected by the filler/binder. Additional experiments
      considering the influence of the compression force (2500 N and 5000 N) and the
      proportion of croscarmellose sodium (1.5%, 3.0% and 6.0%) on the mechanical
      properties of the tablets were performed by a 2 x 3 factorial design. Both
      factors significantly affected the tensile strength, friability and
      disintegration time of the tablets.

PMID- 16599263
TI  - Creatine supplementation improves muscle strength in patients with congestive
      heart failure.
AB  - BACKGROUND: Both, cardiac and skeletal muscle creatine levels are depressed in
      patients with congestive heart failure (CHF). Oral supplementation of creatine
      (Cr) could increase physical performance in healthy volunteers. We therefore
      hypothesized that oral creatine supplementation improves skeletal muscle
      strength, quality of live and symptom-limited performance in patients with CHF.
      METHODS: In a double-blind, placebo-controlled and crossover-designed study, 20
      patients suffering from congestive heart failure more than 6 months and a peak
      oxygen uptake (peak VO2) below 20 ml/min/kg received 4 x 5 g Cr daily vs. placebo
      for 6 weeks and were crossed over for the following 6 weeks. Peak VO2, VO2 at the
      anaerobic threshold (VO2AT), ejection fraction (EF), distance in 6-minute-walk
      test (6 min W), and muscle strength (Modified Sphygmomanometer (MS)) were
      determined at baseline, after 6, and after 12 weeks. Dyspnoea after 6-minute-walk
      test was measured using the Borg Scale. Quality of live was assessed with the
      Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS: 13 of 20
      Patients finished the study. After 6 weeks of creatine supplementation there was
      a significant increase in body weight and muscle strength compared to baseline
      and placebo (p < 0.05). However, there was no significant change in peak VO2,
      VO2AT, walking distance, quality of life assessment and EF. CONCLUSION: Short
      term creatine supplementation inaddition to standard medication in patients with
      CHF leads to an increase in body weight and an improvement of muscle strength.
      This effect is restricted to the time of supplementation.

PMID- 16599264
TI  - Biphasic regulation of angiogenesis by reactive oxygen species.
AB  - Reactive oxygen species (ROS) are believed to be important molecules in the
      regulation of angiogenesis. However, direct evidence is obtained from hydrogen
      peroxide only. The comparison of superoxide anion (O2-), hydrogen peroxide (H202)
      and hydroxyl radical (HO*) effects on angiogenesis in one angiogenic model were
      studied. Tube formation, migration and adhesion of endothelial cells were
      enhanced with a low concentration of O2 generated by 500 [microM xanthine (X) and
      1 mU/ml xanthine oxidase (XO), but significantly inhibited as the XO increased to
      10 mU/ml or more. Low concentrations of H2O2 (0.01-1 microM) induced tube
      formation and the maximal tube formation was achieved at 0.1 microM which also
      induced cell migration and adhesion, while high concentrations of H2O2 (100
      microM) inhibited tube formation and cell migration. Both H2O2 and O2 inhibited
      cell proliferation at high concentration only. HO* at low concentration neither
      inhibited nor stimulated the tube formation, cell proliferation and migration but
      inhibited at high concentration. The effects of O2 were significantly abolished
      by catalase (CAT) alone or in combination with superoxide dismutase (SOD), but
      not by inactive CAT or SOD alone. Active CAT, but not inactive CAT, also reversed
      the effects of H2O2. Pretreatment with GSH effectively reversed the inhibitory
      effects of HO*. Therefore, our results suggest that ROS have biphasic effects on
      angiogenesis, which indicated that pharmacologically regulating cellular ROS
      levels might serve as an anti-angiogenic or angiogenic principles. They also
      provide a theoretical basis for the development and rational use of novel
      angiogenic and anti-angiogenic drugs.

PMID- 16599265
TI  - Comparative studies on hypocholesterolemic effect of different fractions of
      Hyphaene thebaica (Doum) in experimental animals.
AB  - A comparison of different fractions of the fruit of Hyphaene thebaica (Doum) was
      performed in order to investigate their effects on serum cholesterol,
      triglycerides and lipoproteins: HDL (high density lipoprotein) cholesterol and
      Non-HDL cholesterol in normal rats. Female Sprague-Dawely rats were treated
      orally with different fractions of the Doum plant. We used atorvastatin and a
      natural extract of Monascus purpureus as references. The total cholesterol, HDL
      cholesterol, Non-HDL cholesterol and triglycerides were estimated. Three
      fractions of the Doum plant exhibited a highly significant decrease in serum
      cholesterol and Non-HDL cholesterol. One fraction exhibited a highly significant
      decrease in cholesterol level but with only a moderately significant effect in
      decreasing the Non-HDL level. Decreasing Non-HDL, especially LDL, cholesterol,
      can reduce the risk of atherosclerosis and subsequent cardiovascular diseases.
      The natural, safe and non-toxic Doum plant could be of great merit for use as a
      hypocholesterolemic drug.

PMID- 16599266
TI  - Glucose lowering efficacy of the aqueous stem bark extract of Trema orientalis
      (Linn) Blume in normal and streptozotocin diabetic rats.
AB  - The glucose-lowering efficacy of the aqueous stem bark extract of Trema
      orientalis (Ulmaceae) was evaluated both in normal and streptozotocin-induced
      diabetic rats. In normoglycemic rats, the single oral administration of the
      aqueous extract of T. orientalis failed to reduce blood glucose levels while in
      STZ-diabetic rats, the plant extract (38-300 mg/kg) exhibited significant
      hypoglycaemic activity with a maximum effect of 29.67%, 5 hours after
      administration of the 75 mg/kg dose when compared with the diabetic untreated
      group. Glibenclamide was not able to lower blood glucose in STZ-diabetic rats,
      while it significantly lowered the blood sugar in normoglycemic rats. The
      hypoglycaemic property of T. orientalis was also assessed by an oral glucose
      tolerance test (OGTT) in STZ-diabetic rats. The aqueous extract of T. orientalis
      and the reference drug, glibenclamide, (10 mg/kg) produced significant blood
      glucose lowering effects in the diabetic rats when compared to the diabetic
      controls. One week after repeated administration of T. orientalis extract, blood
      glucose levels were significantly decreased (p < 0.05) and still remained low
      after 2 weeks (p < 0.01). The results indicated that T. orientalis stem bark
      extract significantly reduces blood glucose in STZ-induced diabetic rats by a
      mechanism different from that of sulfonylurea agents. The present investigation
      provides pharmacological evidence that the use of this plant extract in
      traditional medicine for cardiovascular disease can be of benefit particulary in
      diabetic patients.

PMID- 16599267
TI  - Antioxidant and photoprotective properties of an extract from buckwheat herb
      (Fagopyrum esculentum MOENCH).
AB  - In recent years, the incidence of skin cancer has risen remarkably. Sun light,
      especially the included ultraviolet (UV)-radiation, is seen as important trigger
      for the development of skin cancer. Thus, there is an increasing interest in the
      development of UV-protective substances to use them as sun care products. One
      approach is the topical application of herbal antioxidants. Plant-derived
      antioxidants are often extracts and therefore contain a complex mixture of
      constituents, like flavonoids and polyphenols, which contribute to the overall
      activity of the extract. In the present study an extract from buckwheat herb was
      compared to rutin, which is the main constituent of the extract, regarding their
      antioxidant and radical scavenging activity. Additionally, the photoprotective
      properties of the extract were compared to those of a commercial UV absorber. The
      antioxidant activity was quantified regarding the reactivity versus the 1,1
      diphenyl-2-picryl-hydrazyl radical (DPPH). The photoprotective properties of the
      extract were examined by the inhibition of the photosensitized lipid peroxidation
      of linolic acid. In the DPPH assay, the extract had significantly better
      antioxidant activity than pure rutin. The extract prevented more effectively the
      UV-induced peroxidation of linolic acid than rutin itself or the commercial UV
      absorber. The use of the extract from buckwheat herb seems to be more beneficial
      than the use of pure rutin. This can be referred to the presence of minor
      phenolic compounds in the extract. The results indicate that it is advisable to
      use antioxidants rather than only UV absorber to obtain a maximum of photo
      protection.

PMID- 16599269
TI  - A new 4-nitrobenzyl carbonate prodrug of methyl 5-benzyl-2-hydroxy-11-methylene-6
      oxo-5H-benzo[b]carbazole-1-carboxylate for potential use with nitroreductase
      based gene-directed enzyme prodrug therapy (GDEPT).
AB  - A tumour-selective 4-nitrobenzyloxycarbonyl prodrug methyl 5-benzyl-2-hydroxy-11
      methylene-6-oxo-5H-benzo[b]carbazole-1-carboxylate was synthezised for gene
      directed enzyme prodrug therapy (GDEPT). The compound is a substrate for E. coli
      nitroreductase.

PMID- 16599268
TI  - Sesquiterpenes with various carbon skeletons from Ligularia virgaurea spp.
      oligocephala.
AB  - Two new 8,9-seco-cacalol-type sesquiterpene lactones, ligulolide C (1 and 2) and
      six known sesquiterpenes, adenostylide (3 and 4), cacalol (5), 1 -hydroxy-2-(3'
      pentenyl)-3,7-dimethylbenzofuran (6), 1beta, 6alpha-dihydroxy-4(14)-eudesmene (7)
      and (+)-oplopanone (8), have been isolated from an extract of the whole plant of
      Ligularia virgaurea spp. oligocephala. The structures of 1 and 2 were confirmed
      by spectroscopic methods including 1D and 2D NMR spectra. A discussion of
      biogenesis of 1 and 2 was described. Cytotoxicity against selected cancer cells
      human promyelocytic leukemia (HL-60), human ovarian (HO-8910) and human lung
      epithehial (A-549) of compounds 1-8 were measured in vitro.

PMID- 16599270
TI  - Determination of valdecoxib in serum using a HPLC-diode array detector and its
      application in a pharmacokinetic study.
AB  - A simple, sensitive, isocratic and reproducible reversed phase HPLC method for
      the determination of valdecoxib, a novel specific COX-2 inhibitor in human serum
      was developed using a diode array detector and celecoxib as internal standard.
      The system consisted of a C18 column and a detector set at 240 nm. The mobile
      phase was a mixture of acetonitrile:water acidified to pH 3.2 with
      orthophosphoric acid (OPA) (60:40) pumped at room temperature and a flow rate of
      1 ml/min. The mean absolute recovery value was about 90%, while the intra (n = 5)
      and inter (n = 5) assay variations were <18%. The calibration was linear over a
      concentration range of 20 ng/ml to 200 microg/ml with r2 > 0.999. The limit of
      detection was < or = 10 ng/ml. The method was used to study the pharmacokinetics
      of valdecoxib after a single dose oral administration to human volunteers.

PMID- 16599271
TI  - Identification of COMT and ErmC inhibitors by using a microplate assay in
      combination with library focusing by virtual screening.
AB  - The paper describes a process of facilitated screening by using a combination of
      molecular modelling and a 96-well microplate assay for the identification of
      novel inhibitors of catechol-O-methyltransferase (COMT) and bacteria expressing
      ErmC. With the help of virtual screening the number of compounds processed in the
      in vitro screening assay was reduced from over 200,000 to 49. Out of the 49, two
      structurally very similar compounds were identified as confirmed hits with
      reasonable activity (IC50 values of 26 and 73 microM) and thus as potential core
      structures for further drug design and development.

PMID- 16599272
TI  - LE300--new results on its ability to antagonize the discriminative stimulus
      effects of cocaine.
AB  - LE300, i.e. 7-methyl-6,7,8,9,14,15-hexahydro-5H-benz-[d]indolo[2,3-g]azecine,
      with nanomolar affinities to the hD1 receptor family, suppresses in vivo
      spontanous locomotor activity and attenuates locomotor activity induced by
      cocaine. Therefore in this study, LE300 was investigated for its ability to
      antagonize cocaine's discriminative effects. LE300 was tested in doses from 0.5
      to 10.0 mg/kg and partially antagonized the discriminative stimulus effects
      produced by 10 mg/kg of cocaine in rats. The partial antagonism (39% drug
      appropriate responding) occurred following 5 mg/kg LE300. Response rate was
      decreased following 5 and 10 mg/kg, with the maximum effect (27% of cocaine
      control) following 10 mg/kg LE300.

PMID- 16599274
TI  - Hard bargaining limits price hikes in raw material costs.

PMID- 16599273
TI  - Phytochemical analysis of nine Hypericum L. species from Serbia and the F.Y.R.
      Macedonia.
AB  - The methanol extracts of the aerial parts of nine Hypericum species (H. barbatum,
      H. hirsutum, H. linarioides, H. maculatum, H. olympicum, H. perforatum, H.
      richeri, H. rumeliacum and H. tetrapterum), collected on different locations in
      Serbia and the F.Y.R. Macedonia, were obtained by accelerated solvent extraction
      (ASE) and analyzed for the content of four constituents (hyperoside, quercitrin,
      hyperforin and hypericin) by LC-MS/ MS. All studied extracts contained the
      characteristic four constituents, but their contents varied between different
      species and locations. The content of hypericin in H. barbatum was significantly
      higher (3.9 times) than that in H. perforatum.

PMID- 16599275
TI  - Medline energy overhaul nets savings.

PMID- 16599276
TI  - Purchasing pros see price hikes in 2006.

PMID- 16599277
TI  - Asianization of dementia research and management: an initiative from Taiwan.

PMID- 16599278
TI  - Electrodiagnosis of the cranial nerves.
AB  - Isolated facial weakness suggests either a contralateral hemispheric lesion or a
      disease of the facial nerve per se. The presence of sensory symptoms usually
      indicates a central facial weakness, which characteristically involves the lower
      part of the face. In contrast, the absence of sensory disturbances suggests a
      peripheral nerve lesion, some system diseases such as amyotrophic lateral
      sclerosis, or a stroke sparing the sensory cortex. Sporadic cases of Bell's palsy
      rank the first in incidence. Although its exact etiology remains unknown,
      accumulating evidence suggests reactivation of herpes simplex virus type I. A
      facial palsy that develops in patients with diabetes mellitus tends to show a
      more severe involvement with substantial denervation. Acoustic neuroma,
      strategically located at the cerebellopontine angle, may compress the facial
      nerve. Peripheral facial palsy may herald other symptoms of multiple sclerosis in
      young adults. Serial electrodiagnostic studies help delineate the course of the
      illness. The amplitude of the direct response elicited by stimulation of the
      facial nerve after the fourth to fifth day of onset serves as the best means
      predicting the eventual outcome of recovery. Blink reflex studies usually show an
      absent or delayed R1, implicating the central reflex arc, which includes the
      intrapontine portion of the facial nerve.

PMID- 16599279
TI  - Congenital myotonic dystrophy: variability in muscle involvement and
      histopathological process.
AB  - In order to understand the involvement of specific muscles in congenital myotonic
      dystrophy type 1 (DM1), we studied the clinical manifestations, and the genetic
      effects on various tissues in 2 siblings with congenital DM1. The distal leg
      muscles were more severely involved than the thigh muscles, as seen in the
      skeletal muscle magnetic resonance imaging. Molecular genetic analysis of the
      myotonic dystrophy type 1 protein kinase showed an elongation of the CTG triplet
      repeats between 850 and 1400 in the leukocytes, skin, fat, tendon, and muscles.
      Muscle biopsies showed a significant difference in the fiber type distribution
      between these two congenital DM1 patients. One revealed a prominent involvement
      of the tibialis anterior muscle with a predominance of type 1 fibers, similar to
      those muscle fiber distributions in older congenital or classic DM1 patients,
      suggesting a neurotrophic influence during muscle development. Another revealed a
      predominance of type 2 fibers in all muscle specimens, and dystrophic changes
      were observed in the peroneus longus muscle indicating a delayed differentiation
      or maturation of muscle fibers. We conclude that despite nearly the same number
      of CTG repeats in the leukocytes, highly individual variability of muscle
      differentiation may occur at teenagers of congenital DM1 in addition to different
      pathological findings in various skeletal muscles of patients with congenital
      DM1.

PMID- 16599280
TI  - Delusions in patients with very mild, mild and moderate Alzheimer's disease.
AB  - PURPOSE: To compare the prevalence of delusions in different stages in Taiwanese
      patients with very mild to moderate Alzheimer's disease (AD). METHODS: A
      consecutive series of 91 patients with probable Alzheimer's disease visited the
      dementia clinic in a regional hospital in mid-Taiwan were enrolled in this study.
      All patients were examined with the Neuropsychiatric Inventory (NPI), the
      Cognitive Abilities Screening Instrument (CASI), and the Clinical Dementia Rating
      (CDR) scale. RESULTS: The prevalence rate of any delusion in very mild, mild and
      moderate AD was 35.2%. Delusions of other persons are stealing was most common
      (27.5%), followed by delusions of self is in danger (15.4%), house is not his/her
      home (5.5%), family plans to abandon him/her (4.4%), spouse is having an affair
      (2.2%), an unwelcome guest is living in the house (2.2%), media persons are in
      the house (2.2%), and others aren't who they claim (1.1%). The prevalence rates
      of delusions is 33% in very mild AD, 30% in mild AD and 48% in moderate AD. AD
      (P>0.05). CONCLUSIONS: Delusions are common neuropsychiatric symptoms in very
      early stage as well as in later stages of Taiwanese patients with AD and it
      deserves the attention that delusions may be characteristic of very mild AD.

PMID- 16599281
TI  - Olfactory neuropathy in severe acute respiratory syndrome: report of A case.
AB  - This case was a 27 years old female with severe acute respiratory syndrome
      (SARS). She suffered from typical symptoms of SARS. Although she got almost
      complete recovery from most symptoms after treatment, she noted acute onset
      complete anosmia 3 weeks after the onset of her first symptom. Her brain MRI
      examination did not show definite lesion except an incidental finding of left
      temporal epidermoid cyst. Her anosmia persisted for more than 2 years during
      following up. Peripheral neuropathy and myopathy have been reported as a
      concomitant problem during the convalescent stage of SARS, while the sequel of
      permanent ansomia in SARS was not reported before. Olfactory neuropathy, which
      rarely occurred in typical peripheral neuropathy, could be a special type of
      neuropathy induced by corona virus infection in SARS. Olfactory function test
      should be taken into routine check-up for patients with SARS. The pathophysiology
      and therapeutic strategy of this special type of permanent olfactory dysfunction
      deserve further investigation.

PMID- 16599282
TI  - Ipsiversive partial ocular tilt reaction in a patient with acute paramedian
      thalamic infarctions.
AB  - The ocular tilt reaction (OTR) consists of skew deviation, ocular torsion and
      head tilt. A 54-year-old woman developed sudden onset of vertical diplopia. On
      primary gaze, there was skew deviation with the left eye higher than the right
      eye. The photography of fundus disclosed 15 degrees of excyclotropia of the right
      eye and 20 degrees of incyclotropia of the left eye. There was no motor deficit,
      sensory impairment, ataxia or changes in consciousness. Brain MRI, including
      T2WI, FLAIR and DWI, revealed two lesions of high signal intensities in bilateral
      paramedian thalamus, with the much larger and brighter one on the right side.
      These findings constituted an ipsiversive partial OTR, i.e. skew and torsion
      toward the side of the lesion. OTR as the only manifestation of paramedian
      thalamic stroke is rare. A previous report by Dieterich and Brandt indicated that
      if an OTR occurred in a paramedian thalamic infarct, there should be concurrent
      ischemia of the interstitial nucleus of Cajal, and it was always contraversive.
      In contrast, the lesions in our case were quite localized in the paramedian
      thalamus, not extending into the midbrain. In addition, this report demonstrated
      an OTR could be ipsiversive under such conditions, opposite to the direction
      mentioned in previous reports.

PMID- 16599283
TI  - Organophosphate intoxication-related coital-like involuntary movements: report of
      A case.
AB  - The neurologic manifestations of organophosphate intoxication are many, and
      different pathophysiologic mechanisms are responsible for the different
      presentations occurring at different stages of the disease process. Movement
      disorders constitute one of the neurologic manifestations, which may include
      Parkinsonism or other dyskinetic movements. However, involuntary coital-like
      movements have not been reported as one of the organophosphate intoxication
      related movement disorders. In this case report, we describe a 71-year-old man
      who developed involuntary coital-like movements about one and a half months after
      an event of organophosphate intoxication in an attempt to commit suicide. The
      involuntary movements were to-and-fro pelvic thrusting and back-rocking
      movements. The patient was able to suppress the involuntary movements for a short
      period of time, although they usually persisted all day long. The involuntary
      movements occurred in all postures including standing, sitting and in supine
      postures, resulting in great embarrassment. These involuntary movements also
      interfered with the initiation of sleep, although they discontinued while asleep.
      With clonazepam and piracetam therapy, the involuntary coital-like movements of
      this patient decreased in amplitude, although remaining to a degree even after
      one year of follow-up.

PMID- 16599284
TI  - Effect of levetiracetam on truncal tic in neuroacanthocytosis.
AB  - We report on an uncommon manifestation of neuroacanthocytosis in a 31-year-old
      woman and the successful use of levetiracetam in the treatment of her
      neurological symptoms. Truncal tic is one of the major presenting features of
      this patient. We find that Levetiracetam, a new antiepileptic drug, was effective
      in eliminating this patient's truncal jerks and motor tic manifestations, such as
      eyelid blinking and head nodding. Levetiracetam can therefore be considered as a
      choice for the symptomatic therapy in neuroacanthocytosis.

PMID- 16599285
TI  - [The application of migraine disability assessment questionnaire (MIDAS)].
AB  - Migraine is a recurring and disabling pain disorder. The prevalence is estimated
      as 9.1% in Taiwan. Patients suffer from significant loss of work, time at school
      or ability to perform household chores, as well as other family or leisure
      activities. Treatment strategies during migraine attacks should be tailored based
      on the severity of disability. Stewart and Lipton (1999) developed the Migraine
      Disability Assessment Questionnaire (MIDAS) to assess the severity of disability
      related to migraine. This simple, self-administered, 7-item questionnaire focuses
      on disability in three domains (school or paid work, household chores, and
      family, social, or leisure activities) in the first 5 items of the questionnaire.
      The internal consistency, test-retest reliability, validity, ease of use, and
      clinical utility were all tested with good results. The questionnaire offers a
      simple tool to improve physician-patient communication. As for treatment
      strategies, a recent large-scale study done in the USA showed that it is more
      efficacious to treat migraine patients by adopting a strategy of stratified care
      based on different disability status than a stepped-care strategy. The simple
      questionnaire, MIDAS, has received world-wide popularity and has been translated
      into Japanese, Italian and Turkish. All of these versions showed good reliability
      and validity. Recently, one of our studies demonstrated that the Taiwan version
      also yielded comparable internal consistency, reliability, and validity. We hope
      that the MIDAS questionnaire can be widely adopted in Taiwan to help physicians
      assess their patients' disability related to migraine and provide clues for
      clinical management.

PMID- 16599286
TI  - Invasive aspergillosis and thrombosis of carotid artery.

PMID- 16599287
TI  - The epidemiology of dementia in Taiwan.

PMID- 16599288
TI  - Insight into management of dementias from neuroimaging.
AB  - Structural and functional neuroimagings are the most powerful tools for
      differential diagnosis and early diagnosis of dementia. Besides clinical use,
      they also contribute to neuroscience and to testing efficacy as surrogate
      measures in clinical trial. This paper, focusing on two different models beyond
      the therapeutic nihilism, discusses the roles of neuroimaging in relation to
      treatment of dementias; 1) treatable "incurable dementia" - Alzheimer's disease
      (AD) and 2) untreated "curable dementia" - idiopathic normal pressure
      hydrocephalus (INPH).

PMID- 16599290
TI  - The neuropsychological studies of dementias in Taiwan: focus on way-finding
      problems in Alzheimer's patients.
AB  - Human urban navigation depends on environmental cognition and the decision making
      to choose route. Impairment of these two components may result in way-finding
      problems, one of the most frequent symptoms in patients with AD. Chiu and her
      colleagues had studies getting lost behavior in AD patients and concluded that
      the getting lost behavior in such patients is in part accounted by their
      executive dysfunction. Pai and his colleagues, on the other hand, used
      experimentally designed tasks to test AD patients what they have called "the
      retrogenetic hypothesis of navigational ability". They have been focused on
      environmental cognition. Recently, they have begun to explore this issue by using
      electrophysiological tools and yielded some results.

PMID- 16599289
TI  - Subjective memory complaints are not sine qua non as diagnostic criteria for MCI:
      the Tajiri project.
AB  - BACKGROUND: To investigate whether subjective memory complaints are sine qua non
      as diagnostic criteria for mild cognitive impairment (MCI), a comprehensive
      approach is required. Information from a memory clinic and an epidemiologic field
      are required, and both are available in the Tajiri Project. METHODS: We report
      two MCI cases, one of a patient complaining of memory decline, and the other of a
      patient without such complaints. Also, epidemiologic data were obtained from the
      healthy and MCI groups, and we analyzed the relationship between the Everyday
      Memory Checklist scores obtained from the participants and their families.
      RESULTS: For both cases, MRI were compatible with Alzheimer's disease (AD), and
      the both actually progressed to clinical AD. Based on the epidemiologic survey,
      two patterns emerged regarding the relationship between subjective complaints and
      family observations: the "anosognosia" pattern associated with the memory
      questions, and the "self-recognition" pattern related to the questions on
      communication problems. CONCLUSIONS: The case studies and the epidemiologic data
      suggest that subjective memory complaints have no significant meaning for
      distinguishing MCI patients from healthy subjects. Hence, we consider that
      subjective memory complaints are not sine qua non as diagnostic criteria for MCI.

PMID- 16599291
TI  - The genetic studies of dementias in Taiwan.
AB  - In Taiwan, Alzheimer's disease (AD) followed by vascular dementia (VsD) is the
      most common cause of dementia among Taiwanese (ethnic Chinese). Several studies
      have documented the increase of risk for AD among the apolipoprotein E gene
      allele 4 (ApoE4) carriers in Taiwanese. It is a consensus that ApoE4 is the most
      important risk factor for AD at present. The researchers also found that ApoE4
      allele frequency is lower in Taiwanese, around 7%, than it in the most Caucasian
      populations. This phenomenon raises the hypothesis that low ApoE4 allele
      frequency contributes to low prevalence of AD in Taiwanese. Besides, many genetic
      studies were involved in genetic impacts on modulation or regulation of the
      manifestation, progression, and treatment response of AD. But, these genetic
      studies are still inconclusive. Few familial AD attributed to PS1 gene mutation
      has been identified. The genetic studies of VsD are just beginning and NOTCH3
      gene mutation has been detected in Taiwanese cerebral autosomal dominant
      arteriopathy with subcortical infarct and leukoencephalopathy (CADASIL) families.
      Since there is a large proportion of non- ApoE4-associated AD in Taiwanese, it
      remains more researches to look for novel genetic factors in Taiwanese. Based on
      the Japanese experience of studies, the association between the polymorphisms of
      ApoE and familial AD, sporadic early-onset AD respectively warrants further
      investigation.

PMID- 16599293
TI  - Interventional studies with the aim of reducing the burden of care through drug
      therapy of BPSD.

PMID- 16599292
TI  - The studies of behavioral and psychological symptoms of dementia in Taiwan.

PMID- 16599294
TI  - The MCI study in Taiwan.
AB  - Veterans General Hospital started study for mild cognitive impairment (MCI) since
      1996. We used clinical dementia rating (CDR) of 0.5 to define our questionable
      dementia (QD) subjects. These QD subjects received annual neuropsychological
      assessment in 5-year follow-up period. Annual conversion rate, apolipoprotein E
      (ApoE) genotype and neuropsychological risk factors for QD were investigated. We
      found a 19.9% person-year conversion rate for these QD subjects. Both of the poor
      cognitive performance and ApoE epsilon4 allele were risk factors for progressing
      to dementia. Based on the results of this study and the progress in the concept
      of MCI, we added more complex verbal and visual memory tests as well as MRI-based
      volumetry measurement in our subsequent research. Peterson's amnestic MCI
      criteria were used to diagnose our MCI subjects. In the 3-year follow-up period,
      the conversional rate was 18.2% person-year for MCI subjects, similar to our
      previous finding in QD. We found hippocampal volume was positively associated
      with cognitive performance. ApoE genotype had effect on hippocampal volume.
      Subjects with lower cognitive performance and smaller hippocampi had higher risk
      converting to AD. With rapidly expanding research on dementia and MCI worldwide,
      we are looking forward to seeing the integration in neurobiology, neuroimaging,
      and neurobehavior fields to establish a multidisciplinary approach to MCI and
      dementia.

PMID- 16599295
TI  - Neurobiological studies of dementia--biological markers and neuroprotective
      strategies for Alzheimer disease.
AB  - Tau protein and amyloid s (Abeta), two major components of neuropathology in
      Alzheimer disease (AD), have been applied for establishment of more useful
      biomarkers and therapeutic approaches. Total tau protein in CSF is a biomarker
      for AD, however increased levels of total tau in CSF were also observed in other
      neurological disease with dementia. Phosphorylation is an important feature of
      tau protein and phosphorylated tau in CSF is useful to distinguish AD from other
      disease. Abeta has toxic effects on neuronal cells, and its mechanisms are
      complicated. One of mechanism of Abeta-cytotoxicity is a down-regulation of XIAP,
      and this effect is observed in the low concentration of Abeta. XIAP might be a
      therapeutic target employing compounds that increase expression of XIAP in
      neuronal cells.

PMID- 16599296
TI  - Differentiated pattern of protein composition of crystalline inclusions of newly
      isolated Bacillus thuringiensis strains from Silesia in Poland.
AB  - Protein profiles of crystal delta-endotoxins were determined in twenty nine
      Bacillus thuringiensis strains-soil and phylloplane isolates--from Poland.
      Electrophoretic analysis revealed quantatively and qualitatively different
      patterns of delta-endotoxin crystal preparations of these B. thuringiensis
      strains. The crystalline parasporal inclusions of B. thuringiensis isolates were
      composed of two, three, four or five proteins. Molecular weights of these
      polypeptides varied from 23.4 kDa to 142 kDa. There is lack of correlation
      between serovars of B. thuringiensis strains, the morphology of crystals and the
      number and size of proteins in parasporal inclusions.

PMID- 16599297
TI  - Influence of N,N-bis(3-aminopropyl)dodecylamine on the mycelium growth and the
      cell wall composition of resistance and sensitive strains belonging to the genus
      Aspergillus.
AB  - Resistance causes of moulds to N,N-bis(3-aminopropyl)dodecylamine (APDA) for
      selected species of Aspergillus niger and Aspergillus flavus was examined.
      Control (sensitive) strains and resistant strains, cultured at 0.05% triamine,
      were used in the experiments. The non-resistant strains did not have growth
      capacity in this amount of ADPA while the resistant strains were characterised by
      a smaller biomass increase. Individual stages of the development of the mycelium
      occurred later than those in the control samples. The participation of the cell
      wall in the mycelium biomass of the resistant strains was higher by 7.5%. The
      glucan content in the wall dry mass was lower by 11% than that in the sensitive
      strains. A 41% increase in the lipid content was recorded in the cell wall of
      resistant Aspergillus flavus. A 21% protein increase occurred in the wall of
      Aspergillus niger comparing to the control strain. Infrared spectrophotometric
      analysis of the cell wall did not reveal the presence of triamine. Most
      absorption bands disappeared in the wall of Aspergillus flavus while no
      additional absorption bands were registered in Aspergillus niger; some bands were
      only stronger than those in the control sample. The resistant strains were
      characterised by a smaller ergosterol content, the main constituent of cell
      membranes. Spectrophotometric analysis of the mycelium did not reveal significant
      qualitative changes; only quantitative changes were observed. It was noticed that
      the resistance reaction did not occur with the same intensity in both species
      studied. The resistant strain of Aspergillus niger was characterised by a
      slightly more intensive absorption within its entire spectrum range in comparison
      to control strain. In case of Aspergillus flavus the absorption was higher for
      control strain.

PMID- 16599298
TI  - The elimination of ochratoxin A by lactic acid bacteria strains.
AB  - The aim of this study was to examine 29 strains of lactic acid bacteria of the
      Lactobacillus and Lactococcus genera, assessing their sensitivity to ochratoxin A
      and their ability to remove it from a liquid medium. It was demonstrated that
      most strains are insensitive to the presence of OTA at the quantity of 5
      microg/disc. It was demonstrated that all strains caused a reduction of the toxin
      amount in the liquid medium. The highest decrease, exceeding 50% of the initial
      OTA content, was caused by the strains Lactobacillus acidophilus CH-5, L.
      rhamnosus GG, L. plantarum BS, L. brevis and L. sanfranciscensis. The example of
      three selected strains confirmed the negative effect of the toxin on the dynamics
      of bacterial growth. A sharp decrease of ochratoxin A was observed during the
      first 15 hours of culture growth. In the course of cultivation the amount of the
      toxin in the medium increased, indicating that the toxin elimination is partially
      reversible. A small quantity of ochratoxin A became bound to the bacterial
      biomass.

PMID- 16599299
TI  - Selection of potentially probiotic Lactobacillus strains towards their inhibitory
      activity against poultry enteropathogenic bacteria.
AB  - Lactobacilli were isolated from chicken gastrointestinal tract and examined for
      their potentially probiotic properties towards their inhibitory activity against
      poultry enteropathogenic bacteria. Biochemical tests, ITS-PCR and cell wall
      protein analysis were used to characterize the Lactobacillus isolates. The
      identification of isolated Lactobacillus strains based on phenotypic properties
      was not always satisfactory. ITS-PCR together with protein profile were found to
      be helpful in strain identification. Lactobacilli were tested for the inhibitory
      activity against selected strains of poultry enteropathogenic bacteria
      (Salmonella Enteritidis, Escherichia coli and Clostridium perfringens). Examined
      supernatants from Lactobacillus broth cultures demonstrated major antimicrobial
      activity against C. perfringens. Lower antimicrobial activity were observed
      against E. coli and Salmonella Enteritidis. The strongest inhibition effect were
      obtained using supernatant of Lactobacillus acidophilus strain 3D. Results
      received from this study confirmed that identification of Lactobacillus spp. is
      often tedious. Some isolates, which are in vitro antagonistic against
      enteropathogenic bacteria may be considered as potential candidates for poultry
      probiotics, especially in controlling necrotic enteritis caused by C.
      perfringens.

PMID- 16599300
TI  - The effect of acid adaptation conditions on heat resistance of Escherichia coli
      O157: H7.
AB  - The objective of this study was to determine the effect of acid adaptation
      conditions on heat resistance of E. coli O157: H7 932. E. coli O157: H7 was
      adapted to acid by exposing the cells to pH 4.5 (2h), pH 5.0 (1 h), and pH 5.5 (1
      h) in tryptic soy broth. D and z values of the acid adapted and control cultures
      at 54 degrees C, 56 degrees C, and 58 degrees C were determined in E buffer. The
      heat resistance of E. coli O157: H7 increased significantly (p<0.05) after acid
      adaptation at pH 4.5 or pH 5.0. E. coli O157: H7 adapted to acid at pH 4.5 for 2
      h had the highest D values at all temperatures tested (20.3-10.7-3.3 min) while D
      values of culture adapted to acid at pH 5.0 for 1 h were 18.2, 7.9, and 2.6 min
      at 54 degrees C, 56 degrees C and 58 degrees C, respectively. Heat resistance of
      culture adapted to acid at pH 5.5 for 1 h and the control culture was not
      significantly different (P<0.05). Culture adapted to acid at pH 4.5 had the
      highest z value (5.10 degrees C), whereas control culture had the lowest z value
      (4.33 degrees C). This study showed that the magnitude of heat tolerance changed
      with the adaptation pH and at low adaptation pH, E. coli O157: H7 showed maximum
      heat resistance. Acid adaptation at pH 4.5 or 5.0 provides E. coli O157: H7 with
      cross-protection against heat treatments, and that this factor must be considered
      to estimate this pathogen's thermal tolerance accurately.

PMID- 16599301
TI  - Co-infection of hamsters with toxin A or toxin B-deficient Clostridium difficile
      strains.
AB  - Male Syrian hamsters (Mesocricetus auratus) were used to study interactions
      between different toxin deficient strains of C. difficile. After sensitization
      with clindamycin, hamsters were intragastrically co-infected with the appropriate
      dilutions corresponding to 100, 1000 and 10,000 cells of four (toxin A or B
      deficient) C. difficile strains (8864, P-829, W-38 and W-74). In addition, a
      group of hamsters was infected with C. difficile VPI 10463, a reference toxigenic
      strain. Colonization and mortality was observed within 48 hours in the group of
      hamsters infected with the reference toxigenic strain. No clinical disease was
      observed in the groups of hamsters co-infected with the toxin A or B-deficient
      strains. Re-infection of these hamsters (co-infected with toxin deficient
      isolates) with C. difficile VPI 10463 resulted in clinical disease and death
      suggesting that these strains do not confer protection against infection with a
      toxigenic strain. Macroscopic and microscopic observations of the cecum of re
      infected hamsters demonstrated uniformly multiple large hemorrhagic areas without
      pseudomembranes. Hamsters infected with as few as 100-500 cells of the toxigenic
      strain--VPI 10463 alone demonstrated pseudomembranes and multiple hemorrhages.
      These results suggest that even though the toxin deficient strains did not
      prevent re-infection with a toxigenic strain of C. difficile, they may play a
      role in the histopathologic changes after re-infections in the hamster model.
      Further studies with a larger number of hamsters and C. difficile strains of
      various molecular profiles are required to better understand the interaction
      between these strains.

PMID- 16599302
TI  - The susceptibility of anaerobic bacteria isolated from periodontal diseases to
      photodynamic inactivation with Fotolon (chlorin e6).
AB  - Photodynamic inactivation (PDI) may be a very promising alternative method for
      the antimicrobial treatment of periodontitis. Several studies have demonstrated
      the sensitivity of subgingival flora to PDI using toluidine blue, methylene blue,
      and chlorin e6 derivatives. In the present study we report the activity of the
      Fotolon sensitizer, composed of chlorin e6 and polyvinylpyrrolidone (PVP),
      against anaerobic bacteria isolated from periodontal diseases. Over 99.9%
      reduction in colony forming units in 20 Gram-positive and 30 Gram-negative
      clinical anaerobic strains was obtained.

PMID- 16599303
TI  - Susceptibility testing and resistance phenotypes detection in bacterial pathogens
      using the VITEK 2 System.
AB  - A set of well characterized strains, collected in Polish hospitals, including
      Gram-negative (n = 93) and Gram-positive (n = 90) isolates was used in the study.
      The VITEK 2 AST-cards were used in the analysis according to the manufacturer's
      recommendations. Comparison of the susceptibility data obtained by the standard
      method and by VITEK 2 cards proved concordant in 99% of cases. Clinically
      important mechanisms were revealed by the VITEK 2 AES with >95% agreement with
      reference data including methicillin resistance in staphylococci (98%), high
      level aminoglycoside resistance in enterococci (100%), VanA and VanB phenotypes
      in enterococci (100%), and ESBLs in Enterobacteriaceae (93.8%). The VITEK 2 AES
      System appears a reliable tool for the detection and interpretive reading of
      clinically important mechanisms of resistance and can be recommended for routine
      work.

PMID- 16599304
TI  - Bacteriological urinalysis in patients after renal transplantation.
AB  - The study consisted of microbiological urinalysis performed in 269 patients after
      renal transplantation who remained under medical care at the Outpatient Service
      of the Transplantation Institute in Warsaw. The patients enrolled into the study
      had undergone renal transplantation 6 to 72 months before urine samples were
      collected. 304 urinalysis were performed. In the group of 269 patients, 42
      individuals had bacteria in their urine what was confirmed in 47 urine cultures.
      Cases of bacteriuria were divided into 5 groups: 5 cases of symptomatic urinary
      tract infection (5 individuals--2% of all studied patients), 27 cases of
      asymptomatic bacteriuria in 22 individuals (8% of all studied patients), 5 cases
      of insignificant bacteriuria in 5 patients (2%), 10 cases of involuntary urine
      contamination in 10 cases (4%). Eventually, urinary tract infection (UTI) was
      established in 27 patients (5 cases of symptomatic UTI and 22 cases of
      asymptomatic UTI) what makes out for 10% of all studied patients. In cases where
      urinalysis showed significant bacteriuria, following pathogens were detected in
      urine cultures: Escherichia coli: 22 strains, Enterococcus faecalis--4 strains,
      Enterobacter cloacae--2 strains and 1 strains of Ralstonia picketii,
      Streptococcus uberis, Pseudomonas aeruginosa and Proteus mirabilis. Over 90% of
      Gram-negative bacteria were susceptible to ceftriaxone and ceftazidime, as well
      as to amikacin and aztreonam which are the drugs usually administered
      intravenously in hospitalized patients. The only drug of similar efficacy, which
      could be administered orally in outpatients was fosfomycin.

PMID- 16599306
TI  - Effect of intensity of feeding on the intestinal microflora of pigs.
AB  - In individual, single-phase feeding animals were fed extensively (group E--7
      animals) or intensively (group I--7 animals) in semi ad libitum system. The
      mixtures differed in composition as well as energy and nutritional value, with
      constant ratio of protein to energy of 13.12:1 in intensive feeding and 13.04:1
      in extensive feeding. Fibre content per 1 kg mixture was 3.43% in group I and
      12.3% in group E. For microbiological studies samples were taken from the
      duodenum, ileum, jejunum and large intestine and both quantitative and
      qualitative differences in the microflora of the differently fed groups was
      found.

PMID- 16599305
TI  - The action of photosensitizers and serum in a bactericidal process. II. The
      effects of dyes: hypericin, eosin Y and saphranine O.
AB  - The aim of the present work was to recognize the reasons for differences in the
      photodynamic action of dyes against various bacterial strains. It is expected
      that a better understanding of this problem may help in design of new
      photosensitizers. The sensitivity of 6 various bacterial strains to the
      photodynamic action of 5 photosensitizers was determined. The hydrophobicity of
      cell surface and susceptibility of bacteria to the natural defense mechanism of
      human serum, were estimated. The differences in the photodynamic efficiency of
      dyes could be contributed to various affinities of cell membrane to dyes, to
      known details of membrane architecture as well as to different mechanisms of
      photosensitization.

PMID- 16599307
TI  - Identification of Aeromonas culicicola by 16S rDNA RFLP.
AB  - Studies were conducted on the improvement of A. culicicola identification. This
      species is phenotypically very similar to A. veronii biotype sobria, A. sobria,
      and A. allosaccharophila. The sequences of 16S rDNA of A. culicicola isolates
      show the highest similarity with A. jandaei, A. veronii, and A. caviae. Digestion
      of 16S rDNA PCR product with AluI and MboI restriction endonucleases allowed
      discriminating A. culicicola from all other Aeromonas species with the exception
      of A. jandaei. Additional digestion of 16S rDNA PCR product with BceAI showed a
      possibility of distinguishing A. jandaei from A. culicicola.

PMID- 16599308
TI  - Analysis of the murein of a Listeria monocytogenes EGD mutant lacking functional
      penicillin binding protein 5 (PBP5).
AB  - Cells of a mutant of Listeria monocytogenes lacking functional PBP5, an enzyme
      with DD-carboxypeptidase activity, make thicker cells walls. In this study we
      show that the muropeptide profile of the mutant, obtained after HPLC analysis of
      a muramidase digest of cell wall murein, differs from that for the wild type
      strain. The main differences embrace strongly reduced disaccharide-tripeptide
      content, strongly increased amounts of pentapeptide-containing muropeptides and a
      shift in profile from less cross-linked muropeptides (monomers, dimers) towards
      more highly cross-linked ones.

PMID- 16599309
TI  - [Cardiac MRI: report on preliminary experience in Sheba Medical Center and review
      of main indications].
AB  - The rapid technical development of cardiac MR imaging in the last decade enables
      us today to evaluate cardiac morphology, function and viability in a reliable and
      very good spatial and temporal resolution. The advanced technology allows us to
      conduct those examinations in an acceptable time for clinical daily use and thus,
      the number of indications for cardiac MR imaging is steadily increasing. Since
      the beginning of 2004, a dedicated cardiac MR scanner has been employed in the
      Department of Medical Imaging in the Sheba Medical Center. We hereby conclude our
      preliminary experience with 58 sequential cases that were referred for cardiac MR
      imaging. Indications for the examination included 17 patients with congenital
      cardiac and great vessels anomalies, 14 patients with a suspected cardiac mass,
      12 patients with suspected right ventricular dysplasia, and 4 patients with
      suspected constrictive pericarditis. This article also includes a review of the
      main indications for obtaining cardiac MR imaging.

PMID- 16599310
TI  - [Evaluation of efficacy, safety and stability of lasik-zyoptix as compared to
      lasik-planoscan in myopia patients with or without astigmatism].
AB  - AIM: To compare the efficacy, safety and stability of laser in-situ
      keratomileusis (LASIK) Zyoptix and PlanoScan (PS) systems for the surgical
      correction of myopia with and without astigmatism. METHODS: In this retrospective
      study we analyzed the results of 198 eyes of 99 patients (randomly chosen) who
      underwent LASIK Zyoptix treatment and 198 eyes of 99 patients (randomly chosen)
      who underwent LASIK PlanoScan standard ablation treatment. Patients were followed
      for a period of 12 months after treatment. All surgeries were performed with the
      Bausch & Lomb Technolas 217z. Data on uncorrected (UCVA) and best spectacle
      corrected (BSCVA) visual acuity, efficacy, predictability, stability and safety
      were analyzed. RESULTS: Mean preoperative spherical error in the Zyoptix group
      was -7.16 D (range= 0 to -16.50, SD = 3.21) and in the PS group -5.31 D (range= 0
      to -16.50, SD=3.13). Mean preoperative cylinder was -1.30 D (range= -0.25 to
      5.00, SD=0.99) and -1.17 D (range= -1 to -4.00, SD=0.85) respectively. Mean
      spherical deviation from expected at 1 year in the Zyoptix group was -0.13 D
      (range= -1.75 to 2, SD=0.73) and in the PS group -0.16 D (range= -4.50 to 2, SD =
      0.75). Mean cylinder at 1 year was -0.69 D (range= -0.50 to 0.75, SD= -0.13) and 
      0.69 D (range = 0 to -2.25, SD = 0.46) respectively. At 1 year, the UCVA in the
      Zyoptix group was 6/12 or better, 6/7.5 or better and 6/6 or better in 87%, 60%
      and 27% respectively, and in the PS group 92%, 64% and 39% respectively.
      CONCLUSIONS: Both treatments can safely and effectively treat myopia and
      astigmatism with stable results up to one year. Zyoptix was found to show better
      outcomes in terms of safety and efficacy.

PMID- 16599311
TI  - [Wavefront-guided lasek after intacs in eyes with stable keratoconus].
AB  - BACKGROUND: Keratoconus is a non-inflammatory, progressive thinning disorder of
      the cornea, resulting in a typical protrusion and in refractive errors and low
      visual acuity. Many of the patients with stable keratoconus encounter
      difficulties wearing glasses or contact lenses. PURPOSE: To evaluate the results
      of wave-front guided laser assisted subepithelial keratectomy (LASEK) for the
      correction of residual spherical and spherocylindrical myopia after INTACS
      insertion in patients with stable keratoconus. METHODS: Four eyes of keratoconus
      patents were treated with Zyoptix wavefront-guided LASEK for correction of
      residual myopia and astigmatism after insertion of INTACS. The refraction after
      insertion of INTACS was stable at least six months before the Zyoptix-LASEK. The
      mean pre-INTACS refraction was myopia of -2.37 D (range 0 to - 5.00 D) and
      astigmatism of -3.93 D (range -1.00 to -7.5 D). The mean refraction prior to
      Zyoptix-LASEK was myopia of -0.2 D and astigmatism of -2.71 D. The mean follow-up
      period after the Zyoptix LASEK was 8 months. RESULTS: Initially, prior to both
      surgeries, the mean uncorrected visual acuity was 6/240 (range count-fingers to
      6/60) and at the final postoperative visit 6/12 (range 6/10 to 6/ 18). The
      preoperative mean best spectacle corrected visual acuity was 6/15 (range 6/10 to
      6/24) and at the final postoperative follow-up visit 6/9 (range 6/8.5 to 6/12).
      CONCLUSION: Zyoptix wavefront-guided LASEK for correction of residual myopia and
      astigmatism in keratoconus patients after INTACS insertion and stable refraction
      provided excellent visual outcome, with no loss of visual acuity and no
      complications.

PMID- 16599312
TI  - [Lasik in myopic patients with congenital nystagmus].
AB  - PURPOSE: To present the results of IntraLASIK treatment in myopic patients with
      nystagmus. METHODS: Four patients, ranging in age from 25 to 49 years, with
      congenital nystagmus (8 eyes), underwent IntraLASIK surgery. Corneal flaps were
      made by Intralase femtosecond laser. In some patients, the eyes were fixated with
      forceps or a fixation ring during the laser ablation. In all patients, the effect
      of involuntary eye movements was neutralized by an active tracking system.
      RESULTS: The refractive errors were corrected in all cases. There was no
      decentration or loss of best corrected visual acuity by more than 1 line. In 3 of
      8 eyes, the post-operative uncorrected visual acuity (UCVA) was equal or better
      than the best spectacles corrected visual acuity (BSCVA) preoperatively. Four of
      the 8 eyes retained or improved their BSCVA. CONCLUSIONS: Some patients with
      myopia and nystagmus may benefit from laser refractive surgery. By using the
      Intralase femtosecond laser and an active tracking system with or without
      mechanical fixation, laser refractive surgery may be safely and accurately
      performed in selected cases of nystagmus. Certain patients improve their BSCVA
      postoperatively.

PMID- 16599313
TI  - [Binocular function and patient satisfaction after monovision induced by laser in
      situ keratomileusis (lasik)].
AB  - INTRODUCTION: Presbyopia is a problem in refraction attributed to loss of near
      vision. Monovision (MV) is a strategy to compensate for presbyopia whereby one
      eye is corrected for distance and the other eye corrected for near vision. The
      patient should be able to suppress the blurred image from one eye and see clearly
      at all distances without glasses. PURPOSE: To measure binocular function and
      patient satisfaction with MV induced by laser in situ keratomileusis (LASIK) in
      myopic and hyperopic presbyopic patients. METHODS: Patients 39 years or older who
      underwent MV LASIK and minimum 90 days follow-up were included in the study. The
      following parameters were used: distance and near corrected/uncorrected visual
      acuity, manifest refraction before and after surgery and near stereopsis
      postoperatively. Patient satisfaction was evaluated by a questionnaire. RESULTS:
      One hundred and fourteen patients (100 myopes, 14 hyperopes) were included. After
      surgery, 79% had distance binocular uncorrected visual acuity of 6/7.5 or better
      and 97% of the patients had near binocular uncorrected visual acuity of J2 or
      better. The median of the near steroacuity was 100 seconds of arc. A total of 80%
      of the patients were very satisfied. The surgical score was 85. An overall 89.5%
      of the patients felt that their main goal had been achieved and 89% would choose
      to have surgery if they had it to do over. Eight percent of the patients used
      glasses for distance and 24% used reading glasses after surgery. The quality of
      life while driving at night improved in 55% and deteriorated in 15% of the
      patients. The quality of life while driving during the day improved in 69% and
      deteriorated in 1%. CONCLUSIONS: Monovision induced by LASIK may be a valuable
      option for both myopic and hyperopic presbyopic individuals considering
      refractive surgery. However, due to the risk of decreased night vision and
      continued use of reading glasses during the day, this surgery may not be suitable
      for patients in whom night driving and/or reading are an essential part of their
      life.

PMID- 16599314
TI  - [Corneal changes after phacoemulsification with a corneal versus a scleral tunnel
      incision].
AB  - AIM: To compare central corneal thickness and endothelial cell loss after
      phacoemulsification with clear cornea and scleral tunnel incisions. SETTING:
      Ophthalmology Department, Toronto Western Hospital, University of Toronto,
      Toronto, Ontario, Canada. METHOD: Fifty-one eyes of 51 patients were randomly
      assigned to one of the two study groups. All patients had central corneal
      thickness measured preoperatively and on post-op days 1, 7, 30 and 90. Specular
      microscopy was performed preoperatively and at 3 months after surgery. RESULTS:
      Cumulative mean central endothelial cell count before surgery was 2,355 +/- 360
      mm2 and 2,305 +/- 376 mm2 post-op. Mean percentage cell loss was 0.82% +/- 19.7%.
      For the scleral tunnel group it was 1.8% +/- 21.5%, and for the clear cornea
      group 0.13% +/- 18.3% (p>0.05). Two-way ANOVA demonstrated no effect of type of
      incision and surgeon on the endothelial cell loss. Pearson correlation
      coefficients between phaco power and cell loss calculated for each of the
      incisions and for each of the surgeons was not significant. Corneal thickness
      increased significantly in all measurements post-op, and returned to baseline by
      3 months. There was no difference in the pachymetry change between the two study
      groups. CONCLUSIONS: Clear cornea and scleral tunnel incisions seem to result in
      no significant difference in endothelial cell loss and or central corneal
      thickness at 3 months post-op.

PMID- 16599315
TI  - [Therapeutic penetrating keratoplasty for microbial keratitis].
AB  - BACKGROUND: Microbial keratitis is a potentially sight threatening disease. Most
      cases respond well to antimicrobial therapy. However, in cases that progress
      despite intensive medical therapy, an urgent therapeutic penetrating keratoplasty
      (TPKP) is required. AIM: To evaluate the indications and results of TPKP in
      Israel. METHODS: A retrospective study reviewed the TPKP performed at the
      Goldschleger Eye Institute, Sheba Medical Center, between 1990-2003. The study
      included 18 cases of at least one-year follow-up. RESULTS: The indications for
      TPKP included severe infectious keratitis unresponsive to medical treatment in
      33% of the patients and severe corneal destruction in 66% of them. The infectious
      keratitis was diagnosed as bacterial keratitis in 44% of the patients,
      unidentified pathogen in 39%, mycotic in 11% and acanthamoeba in 6% of the
      patients. Risk factors in the patients with microbial keratitis requiring TPKP
      included: previous ocular disease in 39%, previous ocular surgery in 66%,
      systemic disorders in 28% and ocular risk factors in 28% patients. TPKP was
      successful in bacterial and acanthamoeba keratitis as far as the transparency of
      the graft and elimination of the infection and improvement of visual acuity.
      However, TPKP failed in mycotic and unidentified keratitis. The risk factors for
      failure included: previous ocular disease or surgeries, systemic disorders or
      large corneal grafts. CONCLUSIONS: Therapeutic penetrating keratoplasty is an
      important and effective therapeutic tool for intractable bacterial and
      acanthamoeba keratitis. Prognostic factors for graft success include lack of
      ocular disease or previous surgeries, lack of systemic disorders or small corneal
      graft size.

PMID- 16599316
TI  - [Goblet cell distribution and epithelial cell morphology in pterygium].
AB  - BACKGROUND: Studies conducted to date on the distribution density of goblet cells
      and epithelial cell morphology in pterygium have yielded contradictory findings.
      OBJECTIVE: To evaluate the density of goblet cells in pterygium and possible
      correlation between clinical and demographic features and goblet cell
      distribution. METHODS: The methodology involved retrospective case series. The
      study sample included 45 consecutive patients undergoing bare sclera operation.
      Biopsy specimens were examined under light microscopy. The goblet cells were
      counted in four fields under X480 magnification and determined by the density
      range. Demographic features were evaluated for every patient. The relationships
      between elastosis, inflammation, congestion of blood vessels and the density
      range in goblet cell count were determined. RESULTS: Distribution density of
      goblet cells was found to be homogenous among cases. In 16 cases (35%) the count
      showed more than 120 cells in a field, while in 13 cases (30%) the authors
      calculated under 15 cells in a field. In 27 cases (60%) there was a high rate of
      elastosis. In only 3 cases (6.6%) the authors found mild dysplasia of the
      epithelium. There was a low rate of congestion of blood vessels in only 5 cases
      (11%). In all cases inflammation was found. There was no significant correlation
      found with all demographic parameters evaluated. CONCLUSION: There is a high rate
      of difference in the distribution and density of goblet cells in pterygia,
      without any correlation with demographic and clinical features listed. There is a
      variable elastosis rate, significant congestion of blood vessels and a low rate
      of dysplasia. All cases presented with chronic inflammatory reaction.

PMID- 16599317
TI  - [Increase in posterior segment depth in eyes with corneal opacities].
AB  - AIM: Studies in animals and in humans demonstrate an increase in axial length and
      induced myopia in eyes with early onset corneal scars. The purpose of this study
      was to compare the total ocular axial length and the length of the anterior and
      the posterior segments, in eyes with unilateral central corneal opacification
      with the unaffected fellow eyes. Elongation of the eye and progressive myopia,
      may lead to both anisometropia and amblyopia. METHODS: In six patients with
      unilateral corneal opacification that developed at an early age, complete eye
      examinations with refraction were performed. Ocular axial measurements were
      determined by A-mode ultrasound. RESULTS: The mean ocular length was greater in
      eyes with central corneal opacities compared with the fellow eyes (27.53 vs.
      23.38 mm; p < 0.003), due to elongation of the posterior segment (19.75 mm vs.
      15.87 mm; p<0.008). No significant change was found in the length of the anterior
      segments. CONCLUSIONS: Our study showed an ipsilateral increase in the posterior
      segment length in patients with unilateral corneal opacification which had
      occurred in childhood. The cause is unknown but may be due to altered visual
      input. Progressive myopia in corneal leukoma is a factor to be taken into account
      in the follow-up and treatment of patients with central corneal opacities that
      occurred in childhood.

PMID- 16599318
TI  - [Cardiac imaging using MRI and CT].
AB  - Recent technical improvements in CT and MRI scanners allow improved imaging of
      the heart and the coronary arteries. These methods will probably replace some of
      the traditional diagnostic methods: echocardiograms, nuclear medicine SPECT
      studies and invasive coronary angiograms. There are several established clinical
      applications for both CT and MRI. Their adoption, however, has been slow, mainly
      for two reasons: the technology has not been widely available, and the clinicians
      lack detailed knowledge about the diagnostic capabilities of each modality. In
      this paper the main applications of each modality are presented based on the
      inherent technical advantages. The main indications for cardiac CT are: calcium
      scoring, anomalies of the coronary arteries, assessment and quantification of
      arterial stenosis, stent patency evaluation, bypass surgery follow-up, myocardial
      bridging, pulmonary and cardiac veins assessment (for ablation), characterization
      of atheromatous plaques (soft, lipoid or calcified), assessment of the lungs,
      mediastinum and thorax. The main indications for cardiac MRI: functional
      evaluation of the left and right ventricle, assessment of myocardial viability by
      perfusion, grading of valvular disease, congenital heart disease diagnosis and
      post-surgical evaluation, cardiomyopathies, diagnosis of myocarditis, coarctation
      of the aorta, diagnosis of cardiac tumors and thrombi, and pulmonary veins
      evaluation. Based on the knowledge of each modality, advantages, performance and
      cost, the referring physician can use evidence based algorithms that will allow
      him/her to tailor the appropriate study for each clinical problem.

PMID- 16599319
TI  - [Anterior cruciate ligament injuries].
AB  - Anterior cruciate ligament (ACL) injuries are common, especially in young
      individuals who participate in sports activities associated with pivoting,
      decelerating and jumping. About 70% of ACL injuries do not result from direct
      contact. Establishing risk factors is important for prevention strategies. Risk
      factors for ACL injuries include environmental factors (e.g. high level of
      friction between shoes and the playing surface) and anatomical factors (e.g.
      narrow femoral intercondylar notch and increased joint laxity). History taking
      and physical examination provide the basis for diagnosis. Magnetic resonance
      imaging (MRI) is highly sensitive and specific and provides information about
      associated injuries such as meniscal tears. ACL-injury leads to knee instability
      which is associated with both acute dysfunction and long-term degenerative
      changes, such as osteoarthritis and meniscal damage. Surgical treatment of ACL
      tears is effective in regard to short term rehabilitation but does not
      necessarily alter the natural course of this injury and its long-term
      complications. Therefore, surgical treatment should be reserved primarily for
      young individuals and for those who are high risk for ACL injury. ACL
      reconstruction is the standard surgery; however, a wide variety of reconstruction
      procedures is available and a gold standard procedure has not been defined.
      Nevertheless, arthroscopic reconstruction with either bone-patellar tendon-bone
      or a hamstring tendon graft is the most widely used method. Surgical timing is
      important. Early surgical intervention (i.e. within 4 weeks of injury) might
      increase complications.

PMID- 16599320
TI  - [Vulvar pain syndrome (vulvodynia)--dilemmas in terminology].
AB  - BACKGROUND: In recent years there has been increasing awareness of chronic vulvar
      pain, both in the medical and lay communities. The etiology of vulvar pain is
      largely unknown. Furthermore, there is no worldwide consensus regarding the
      terminology and classification of this condition, which makes it difficult to
      compare the results of different treatments. In 2003, following more than three
      decades of uncertainty, the terminology and classification of vulvar pain was re
      established. AIM: To review the development of nomenclature for vulvar pain and
      the increasing understanding of its pathophysiology. METHODS: A literature review
      was conducted of articles related to the nomenclature of vulvar pain and vulvar
      diseases, and a summary of the world congresses of the International Society for
      the Study of Vulvovaginal Disease (ISSVD) from 1976 until 2003. RESULTS: In 1976,
      members of the ISSVD recognized vulvar pain as a unique entity, and called it
      burning vulva syndrome. In 1985, the ISSVD renamed this disorder "Vulvodynia" and
      classified it into two clinically distinctive subsets: dysesthetic vulvodynia and
      vestibulitis. However, recent studies failed to confirm an inflammatory
      pathogenesis, and the term vestibulitis was replaced by the term vestibulodynia
      at the 1999 ISSVD congress. In 2003, the ISSVD reviewed the terminology and used
      the term vulvodynia, which is further classified as either generalized or
      localized, and by the presence or absence of stimulus for pain. CONCLUSIONS: The
      re-establishment of the ISSVD terminology and classification in 2003 will help
      physicians and researchers improve the understanding of chronic idiopathic vulvar
      pain, and develop effective treatments.

PMID- 16599321
TI  - [Tamoxifen treatment and malignant endometrial tumors--what's new?].
AB  - Breast cancer is the most common cancer among women in the western world. The
      dramatic change in mortality due to breast cancer in the last decade was
      associated with better screening for early detection of malignancy and improved
      hormonal anti-estrogenic adjuvant therapy, mainly Tamoxifen. However, in the
      endometrium, Tamoxifen has a proestrogenic effect. Among women treated with
      Tamoxifen, a wide range of endometrial pathologies was documented--from polyps
      and hyperplasia to malignant tumors. Hence, there is still a debate on the
      character of malignant tumors developing under the influence of Tamoxifen
      treatment. Moreover, there are no clear guidelines considering the evaluation of
      the endometrium in women treated by Tamoxifen. These issues are discussed in this
      review.

PMID- 16599322
TI  - [Assisted reproduction technologies and the risk of fetal, chromosomal and
      genetic malformations].
AB  - BACKGROUND: Assisted reproduction techniques allowed thousands of otherwise
      infertile couples to attain pregnancy. As this technology moves into the
      mainstream of infertility treatment, it has become more critical to reassess its
      safety. OBJECTIVE: To review the birth outcome of patients undergoing
      conventional in-vitro fertilization and intracyto- plasmic sperm injection
      regarding fetal malformations, chromosomal and genetic abnormalities. METHODS:
      Selective review of the literature. RESULTS: Most of the published data is from
      observational studies and is not randomized or blinded. Unfortunately, most
      articles are inherently biased. Chromosomal and genetic abnormalities are
      increased probably only as a direct corollary to the underlying parental risk and
      not due to the technology itself. There is a slight increase in the congenital
      malformations rate, but inspection of these malformations reveal no clustering of
      any specific abnormality. CONCLUSIONS: Children born after assisted reproduction
      technologies have an increased risk of a major congenital malformation and
      chromosomal abnormalities compared with those born after natural conception. The
      risk is mainly due to paternal and maternal risk factors, which are more
      prevalent in couples who use assisted reproduction techniques for reproduction.
      Infertility-linked risk is highly probable for the observed findings. A technique
      related risk, however, cannot be ruled out. Intracytoplasmic sperm injection
      appears to be a safe alternative for couples who otherwise would be unable to
      achieve pregnancy. The inherent risks associated with these genetically "at risk"
      couples mandate thorough evaluation and counseling before undertaking ICSI.

PMID- 16599324
TI  - [Dentistry in Israel].

PMID- 16599323
TI  - [Mild cognitive impairment (MCI): characteristics, risk factors and prevention].
AB  - Mild cognitive impairment (MCI) is a term describing the individual's cognitive
      state, ranging from normal aging to dementia. Since the term MCI was only
      recently introduced, there are still controversies regarding its definition,
      frequency and characteristics. Despite ambiguity in the clinical definitions, MCI
      is strongly considered as representing enhanced risk for the development of
      dementia. Therefore, MCI seems to be an important target phase for clinical
      intervention aimed at inhibiting deterioration to dementia. Despite the
      controversies regarding the diagnosis of MCI and its exact definition, great
      progress has been achieved in identifying brain changes, genetic risk factors and
      prevention factors associated with MCI.

PMID- 16599325
TI  - [Community aspects of geriatric dentistry--a literature review: 1975 - 2000].
AB  - The world's population is in transition, but there is an inevitable move in all
      societies towards an aging population. There is an agreement that the ability of
      the geriatric population to adjust to the "third age" depends on the will of the
      society and the community to provide services and to support this vulnerable and
      dependent population. The preponderance of oral health issues and their impact
      upon general health and quality of life have prompted a variety of geriatric
      related efforts over the last 20 years. Predoctoral and postdoctoral education
      and training efforts have been initiated, geriatric research agendas have started
      to yield important findings, and a few service programs have marginally helped
      improve dental care access for the geriatric population. Past discoveries have
      enabled large portions of the world's population to enjoy far better oral health
      than their forebears a century ago. Although different patterns of dental needs
      emerge throughout the world, the" silent epidemic" of oral diseases is affecting
      the most vulnerable parts of the population: the poor children, the elderly and
      many members of racial and ethnic minority groups. The review of the literature
      of community aspects of geriatric dentistry in the past twenty five years will be
      introduced in two articles. The first article summarizes the important issues of
      demography, oral health condition, changes in attitude towards oral health of the
      geriatric population, oral health services given in geriatric institutions and
      mobile dentistry. The issues of law and ethics, development of public and
      community oral health programs for the geriatric population and plans as well as
      trends for the future will be discussed in the second article. Setting goals and
      presenting data are steps in the right direction but are not enough; the success
      will be measured by the ability to make things happen. The continuing anticipated
      growth of the geriatric population will, hopefully, be translated into a rising
      political power and to fruitful and practical health outcomes.

PMID- 16599326
TI  - Dental meeting languages and dentists/populations ratio in Africa.

PMID- 16599327
TI  - Dental status among native and immigrant young Israeli adults.
AB  - BACKGROUND: New immigrants, originating from different cultures, often
      demonstrate dental health, behavior and treatment levels, which are different to
      native born populations. Immigrants are often classified as 'high-risk'
      populations. The goals of this study included comparing caries prevalence levels
      and different modes of treatment and dental health behavior, among immigrants
      from the former USSR and Israeli born young adults. METHODS: 581 young adults
      (average age 18 years) answered a questionnaire and were clinically examined.
      RESULTS: Socio-demographic variables were significantly different: number of
      siblings and years of schooling were higher among the Israeli born population;
      father's occupation was less professional among the immigrants. Untreated caries
      and lower father's occupation were significantly associated. Most immigrants
      reached the dentist's office only when they suffered pain, in contrast to the
      Israelis who were more regularly taken care of. Smoking was more prevalent among
      immigrants and significantly associated with caries levels. The caries prevalence
      among the Israelis was: DMFT = 4.7 +/- 4.13, D = 1.09 +/- 1.81, M = 0.11 +/-
      0.37, F = 3.51 +/- 3.85, and among the immigrants: DMFT = 5.98 +/- 4.66, D = 2.78
      +/- 2.77, M = 1.01 +/- 0.51, F = 2.70 +/- 3.22. These differences were
      statistically significant (p<0.005). CONCLUSIONS: Immigrants should be considered
      as a high risk group and demand a specific call for public health action.

PMID- 16599328
TI  - [Vertical root fractures in endodontically treated teeth part I: clinical and
      radiographic diagnosis].
AB  - A correct and quick diagnosis of endodontically treated vertically fractured
      teeth is important for two main reasons: (1) the differential diagnosis between
      the clinical and radiographic appearance of periodontal disease and endodontic
      failures, and (2) the delay in making the correct diagnosis will result in rapid
      loss of supporting bone, especially on the buccal side. Typical clinical signs in
      the maxillary and mandibular premolars and mesial root of the mandibular molars,
      which are the most susceptible roots and teeth, for fracture are a highly located
      sinus tract and a deep bony defect along the root facing the fracture line. In
      the maxillary and mandibular premolars and the mesial root of mandibular molars,
      typical bony radiolucencies are the halo, vertical and periodontal types.
      Radiolucency in the bifurcation was typical in vertical root fractures of
      mandibular molars.

PMID- 16599329
TI  - [Decoronation: indications and treatment timing].
AB  - Dental trauma in children is a frequent event and may involve functional,
      esthetic and orthodontic complications. Replacement resorption and ankylosis are
      frequently diagnosed following avulsion and replantation, severe intrusive
      luxation, and less frequently as a consequence of lateral luxations and root
      fractures. The optimal treatment for an ankylotic permanent incisor is yet to be
      found. The treatment of ankylosis and replacement resorption of a permanent
      incisor following dental trauma is further complicated when it involves a growing
      child. It is often associated with increasing infraposition of the tooth,
      retarded growth of the alveolar bone and tilting of adjacent teeth. To avoid such
      complications an ankylosed tooth should be removed before they changes become so
      pronounced that they necessitate orthodontic intervention and compromise future
      prosthetic treatment. The purpose of this article is to review the literature
      dealing with the considerations involved in the treatment of a permanent incisor
      diagnosed with replacement resorption and ankylosis. Different treatment options
      are considered. Decoronation is described and discussed.

PMID- 16599330
TI  - [Simple bone cyst in the mandible--a rare occurrence in an elderly patient].
AB  - Simple bone cyst (SBC) is an intra-osseous pseudocystic lesion lined by a thin
      fibrovascular membrane but lacks an epithelial lining. SBC is uncommon and
      comprises of approximately 1% of all jaw cysts. The lesion is usually discovered
      incidentally during the first two decades of life. Males are affected slightly
      more frequently than females. The most common sites of occurrence are the molar
      and premolar regions of the mandible; maxillary lesions are uncommon. The lesion
      is usually solitary, radiolucent, well demarcated, and non-expansile. Margins may
      be scalloped, between vital teeth, and root resorption is rare. A surgical
      approach to the lesion reveals an empty cavity with serosanguinous fluid.
      Histologically, the cavity lining consists of a loose connective tissue layer and
      hemosiderin-laden macrophages. Pathogenesis and etiology of SBC are still not
      clearly understood. It is assumed that the cyst forms following traumatic intra
      osseous hemorrhage with subsequent lysis and resorption of the cellular content.
      Trauma, as the main cause of SBC, is not always conclusive and the origin of the
      lesion may be multifactorial. Treatment of SBC is by curettage. Intralesional
      hemorrhage due to either intentional curettage or during exploratory procedure
      may induce a reparative process. A rare occurrence of SBC in a 71 year old
      healthy male, referred to the Oral and Maxillofacial Outpatient Clinic, Sheba
      Medical Center by his dentist, because of a large radiolucent lesion in the left
      mandibular body is reported. The patient received a complete lower denture 3
      months earlier. He returned to his dentist with a complaint of local pain and an
      ulcer under the denture. A panoramic radiograph revealed a large unilocular
      radiolucent lesion with demarcated borders in the left mandibular body and bone
      erosion in the upper alveolar border of the lesion Clinical examination showed a
      deep ulcer in the denture-bearing area of the left posterior alveolar ridge.
      There was no cortical expansion of the mandible. Incisinal biopsy revealed an
      empty cavity lined by fibrous connective tissue with no epithelial lining.
      According to the clinico-radiologic and histologic findings, a diagnosis of a
      simple bone cyst was made. The incidence of SBC is higher in younger age groups
      (second decade). Occurrence of the lesion in the elderly is rare with only a few
      reports in the literature. In the present case, the fact that SBC is
      asymptomatic, may be responsible for the late discovery of the lesion.

PMID- 16599331
TI  - [Atrophic ridge augmentation using intra-oral onlay bone grafts--expanding the
      limits].
AB  - Placement of an endosseous implant requires sufficient bone volume for complete
      bone coverage. There is a growing use of intraoral block bone grafts from
      intraoral sources. The use of bone from the mandibular symphysis, retromolar
      area, mandibular ramus, and the maxillary tuberosity can serve as a good
      treatment alternative for alveolar ridge augmentation with a high success rate
      for long span augmentation, up to complete jaw augmentation or extensive bone
      reconstruction. The intraoral block bone graft procedure can be combined with
      other surgical procedures, such as sinus lift elevation or nasal floor elevation.

PMID- 16599332
TI  - [Survey of patient satisfaction at the Yad Sarah Geriatric Dental Clinic].
AB  - OBJECTIVES: The purpose of this study is to determine the influence of a
      supporting professional environment, in a voluntary dental clinic, on the
      satisfaction among dental patients. METHODS: A sample of 109 patients who
      received dental care between 3/01-3/02 at the Yad Sarah dental clinic in
      Jerusalem were asked about : their satisfaction concerning their experience of
      previous visits, the frequency of their visits, how they heard about the clinic
      and whether they would return to the clinic in the future. RESULTS: On average,
      each patient visited the clinic three times. 36.7% of the patients heard about
      the clinic from friends or family. Most of the patients were highly satisfied
      (47.2%) or satisfied (36.1%) with the clinic. The two best predictors of patient
      satisfaction (total 83.2%) were the professionalism of the dentists (41.4%) and
      the good attitude of the dentists to them. On the other hand, the two best
      predictors of patient non-satisfaction (14%) were the low professionalism of the
      dentists (33.3%) and the price of the treatments at the clinic (33.3%). 89% said
      they would return to the clinic and 93% said they would recommend that other
      patients use the services of Yad Sarah dental clinic. CONCLUSIONS: Overall, the
      patients who were treated at the Yad Sarah dental clinic expressed high levels of
      satisfaction with the care they received. The professionalism and the attitude of
      the staff were the main contributors to the high level of satisfaction with the
      Yad Sarah dental clinic.

PMID- 16599333
TI  - [Full arch impression techniques utilizing addition type poly vinyl siloxane for
      fabrication of tooth born fixed partial dentures].
AB  - A precise impression is necessary for fabricating an accurately fitting cast
      restoration. For this purpose, Polyvinyl Siloxane (PVS) impression materials are
      extremely popular because of their combination of excellent physical properties,
      handling characteristics and dimensional stability. Its excellent clinical
      features remain unaffected if simple measures are guarded. This review presents
      several impression techniques using PVS and recommends the one that provides the
      most accurate impression, utilizing the superior qualities of the PVS. The one
      step impression technique where no control of wash bulk and thickness exists, is
      considered to be the least accurate impression method with measured discrepancies
      as large as 7 times the original inter preparation distance and 40 times the
      original cross arch dimensions. Furthermore, the direct contact between the less
      refined putty material and the tooth preparation, as well as the high prevalence
      of air bubble entrapment, seriously compromises restoration longevity. The two
      stage impression technique has proved to produce the most accurate and reliable
      impressions due to complete control of the wash bulk and thickness entailed. The
      ideal wash bulk thickness should range between 1 to 2.5 mm all around the
      abutment tooth in order to minimize distortion of its subsequent die. Using a
      "Putty Tray" at the first stage with a predetermined space encircling the
      abutments will allow the wash to flow to its ideal uniform bulk size at the
      second stage. A uniform bulk size will prevent differential setting contraction
      and uneven changes at the dimensions of the die. The easiest and most clinically
      applicable method to achieve the desired space around the preparations is by
      loading the Putty material with the temporary crowns in place, followed by their
      removal at the second stage and occupation of the created space by the wash. In
      general, less control of wash bulk will result in either insufficient or
      excessive wash material which will determine uneven dimensional changes in the
      impression. This, in turn, will produce ill fitting cast restoration.

PMID- 16599334
TI  - [Caries definition throughout the years].

PMID- 16599335
TI  - Shedding light on the situation.

PMID- 16599336
TI  - Fitting in. Mass General's Yawkey Center makes the most of a limited site.

PMID- 16599337
TI  - Making the case. Selling energy management initiatives to executives.

PMID- 16599338
TI  - The boom goes on. Technology and consumer demands keep driving construction and
      renovation.

PMID- 16599340
TI  - Look out below. Establishing a systematic approach to floor cleaning.

PMID- 16599339
TI  - What's new in the LSC? A look at the 2006 NFPA /LIFE SAFETY CODE/ revisions.

PMID- 16599341
TI  - Factorial validity and invariance of the center for epidemiologic studies
      depression (CES-D) scale in a sample of black and white adolescent girls.
AB  - Meaningful comparison of depression symptoms requires that the measurement
      instrument has equivalent measurement properties among racial and ethnic groups.
      We tested the factorial validity and invariance of the Center for Epidemiologic
      Studies-Depression (CES-D) Scale among Black (n=610) and White (n=452) adolescent
      girls in the 12th grade. The invariance analyses were conducted by using LISREL
      8.70 with maximum likelihood estimation and Satorra-Bentler scaled chi-square
      statistics and standard errors. The hypothesized second-order model (first-order
      factors: depressed affect, somatic and retarded activity, interpersonal, and
      positive affect; second-order factor: depression) demonstrated good overall fit
      in both groups. Comparison of nested models supported the between-group
      invariance of the overall factor structure, first- and second-order factor
      loadings, first-order factor variances, and the second-order factor variance.
      Item uniquenesses were not invariant. Our results support the hypothesis that a
      meaningful comparison of composite CES-D scores can be made between Black and
      White girls in the 12th grade.

PMID- 16599342
TI  - Apolipoprotein E and cognition in community-based samples of African Americans
      and Caucasians.
AB  - To compare relative frequencies of apolipo-protein E (APOE) alleles in African
      American and Caucasian populations and test associations with cognition, we
      studied two community-based samples: one of 253 African Americans and another of
      466 Caucasians age 60-84 years. Logistic regression, adjusting for age, sex,
      education, and history of hypertension and diabetes was used to associate APOE
      with five cognitive measures. The APOE-epsilon4 allele frequency was 29.5% in
      African Americans and 12.1% in Caucasians. In the African Americans, no
      association was found between the presence of the APOE-epsilon4 allele and any of
      the cognitive measures. Among Caucasians, APOE-epsilon4 carriers performed more
      poorly on three of the five tests. We also report a considerably higher frequency
      of the APOE-epsilon4 allele in our African-American sample compared to other US
      based studies.

PMID- 16599343
TI  - Sleep disturbance mediates the relationship between perceived racism and
      depressive symptoms.
AB  - OBJECTIVES: To examine the effects of racism on sleep disturbance and depression
      and to examine whether sleep disturbance mediates the effects of racism on
      depression. DESIGN: Cross-sectional questionnaire study. SETTING: Community.
      PARTICIPANTS: 168 Hispanic-American immigrants, 45% female, average age 33 years,
      average length of time living in the United States was 5 years. MEASURES: The
      Perceived Racism Scale for Latinos, the Pittsburgh Sleep Quality Index, and the
      Center for Epidemiologic Studies-Depression (CES-D) Scale. RESULTS: Using
      hierarchical linear regression analyses, perceived racism was related to
      increased sleep disturbance (b=.21, P<.01) and higher levels of depressive
      symptoms (b=.24, P<.01). When sleep disturbance was included in the regression
      equation, perceived racism was no longer a significant predictor of depressive
      symptoms (b=.10, nonsignificant), indicating that sleep disturbance mediated the
      relationship between perceived racism and depressive symptoms. CONCLUSIONS: This
      study adds to the research literature by identifying sleep disturbance as a
      potential pathway through which perceived racism may affect health.

PMID- 16599344
TI  - Anxiety in persons 75 and older: findings from a tri-ethnic population.
AB  - PURPOSE: Little research has been reported about anxiety in older populations. We
      assessed the prevalence of anxiety and examined associations between anxiety and
      sociodemographic, physical, mental, and functional health characteristics in an
      older tri-ethnic population. DESIGN AND METHODS: A cross-sectional, population
      based study of older, noninstitutionalized non-Hispanic Whites, non-Hispanic
      Blacks, and Hispanics was conducted from the baseline assessment of the Health of
      the Public (HoP) database. Measurements included a self-report anxiety scale and
      physical, mental, and functional health. Data were analyzed with general linear
      models and logistic regression models. RESULTS: Overall, 31.4% reported anxiety
      (score > or = 45); 32.3% of woman and 30.5% of men (P=.67). Older Hispanics
      (22.2%) reported the lowest prevalence of anxiety followed by non-Hispanic Blacks
      (26.6%) and non-Hispanic Whites (44.3%) (P=.0001). Common predictors of anxiety
      seen after linear and logistic regression included being married, White, and
      increasing number of medications and depressive symptoms. IMPLICATIONS: Anxiety
      is prevalent in older adults. The findings also indicate higher rates of anxiety
      in older non-Hispanic Whites compared with older non-Hispanic Blacks and
      Hispanics.

PMID- 16599345
TI  - Racial and ethnic disparities in medical history taking: detecting substance use
      among low-income pregnant women.
AB  - OBJECTIVE: To determine whether providers' medical history-taking of substance
      use varies with their patients' race or ethnicity. DESIGN/SETTING/PARTICIPANTS:
      The medical records of 1083 low-income women who delivered at an urban teaching
      hospital over a 12-month period were reviewed and data were abstracted. The
      frequency with which the presence or absence of substance use was documented was
      compared among Black, Hispanic, and White women. Multivariate models predicting
      documentation of data on substance use were also built. RESULTS: Information on
      substance use was more often documented in the medical records of Black and
      Hispanic women than in those of White women. For example, 74% of Black women, 78%
      of Hispanic women, and 60% of White women had data on cocaine use documented in
      their medical records (P= .0001). Multivariate analyses found that, after
      controlling for other factors, Black (odds ratio [OR] 4.1) and Hispanic (OR 5.3)
      non-clinic patients were more likely than White non-clinic patients to have
      documented data on substance use history in their medical records. No racial/
      ethnic disparities were found among clinic patients. Among White women, clinic
      patients were more likely than non-clinic patients to have documented data on
      substance use. Among other races and ethnicities, no disparities were found
      between places of care. CONCLUSIONS: The differential collection of information
      on women's medical histories may be influenced by organizational factors and/or
      provider factors. The standard implementation of history-taking protocols would
      reduce the influence of institutional and personal biases on the care provided to
      pregnant women and enable all patients to receive appropriate referrals to
      treatment.

PMID- 16599346
TI  - Beliefs and attitudes regarding smoking cessation among American Indians: a pilot
      study.
AB  - BACKGROUND: American Indians (AI) have some of the highest smoking rates in the
      United States. The Muscogee Nation of Oklahoma developed a culturally targeted
      program called "Second Wind" based on the American Cancer Society's FreshStart
      smoking cessation program, but it has not been formally tested. METHODS: We
      conducted six focus groups of AI adult smokers at the Haskell Health Center
      (Lawrence, Kansas). Focus groups assessed beliefs, attitudes, and behaviors
      related to smoking cessation, as well as participants' perceptions of the "Second
      Wind" curriculum's appropriateness and feasibility for this diverse group. Focus
      groups were audiotaped, transcribed, coded, and analyzed for content themes.
      Participants were 41 AI adults (63% female), 21-67 years of age. Participants
      smoked an average of 13 cigarettes per day, half had made a quit attempt in the
      past year, and 63% were daily smokers. For pharmacotherapy, most preferred the
      nicotine patch. RESULTS: Focus group responses were categorized into three major
      themes: traditional tobacco use, quitting and quit attempts, and the "Second
      Wind" program. Those who reported that traditional tobacco use is important were
      less inclined to use tobacco recreationally. Second Wind modifications suggested
      by participants included increasing use of AI imagery and addressing the meaning
      of tobacco to AI cultures. CONCLUSIONS: American Indian smokers are unique
      because of their traditional use of tobacco. Our participants felt that smoking
      cessation can be accomplished without discouraging traditional use of tobacco. We
      suggest ways to improve the "Second Wind" curriculum so that it is targeted for a
      heterogeneous group of AI smokers.

PMID- 16599347
TI  - Gender differences in depression and smoking among youth in Cape Town, South
      Africa.
AB  - OBJECTIVE: Gender differences in the association between depression and smoking
      has received inconsistent support among youth in national samples in the United
      States and other countries. However, the examination of depression and smoking
      among South African male and female youth has not been sufficiently studied. This
      paper examines gender differences in the association between depression, racially
      classified social group (RCSG) status, social amenities, and grade level with
      smoking among South African youth in Cape Town. DESIGN: Six-hundred twenty
      students completed a questionnaire on socio-demographic characteristics, smoking,
      and depression. Separate logistic regression procedures were conducted by gender
      to assess significant variations in correlates of ever smoker versus never smoker
      status and current smoker versus nonsmoker status. Variables included in the
      models were Beck Depression Inventory scores, RCSG, social amenities, and grade
      level. RESULTS: Primary analyses revealed that among girls, mild and severe
      depression were significant predictors of ever smoking status. In addition, girls
      who suffered from mild, moderate, and severe forms of depression were more likely
      to be current smokers than nonsmokers. Among boys, depression was not a
      significant predictor of smoking status. CONCLUSIONS: The results support the
      need to incorporate mental health education strategies into smoking intervention
      programs, especially among school girls in Cape Town, South Africa.

PMID- 16599348
TI  - Role of thiazolidinediones in the management of type 2 diabetes: focus on ethnic
      minority populations.
AB  - Persons from ethnic minority populations in the United States suffer
      disproportionately more from type 2 diabetes and its complications than do
      Caucasians. Genetic and acquired factors likely contribute to the ethnic
      disparities of type 2 diabetes. The pathophysiologic hallmarks consist of insulin
      resistance, progressive pancreatic beta-cell dysfunction, and excessive hepatic
      glucose production. The ideal treatment for type 2 diabetes should correct
      insulin resistance and beta-cell dysfunction; and normalize hepatic glucose
      output; and prevent, delay, or reverse diabetic complications. The discovery of a
      new class of drugs, thiazolidinediones, has provided an effective tool to correct
      key underlying defects in type 2 diabetes. Thiazolidinediones improve insulin
      sensitivity and have beneficial effects on pancreatic beta-cell function and
      hepatic glucose production. Furthermore, their potent insulin-sensitization
      effect predicts that treatment with thiazolidinediones will improve
      cardiovascular risk factors, including lipid profile, fibrinolysis, endothelial
      function, and atheroinflammatory markers. These benefits are expected to be
      particularly important among ethnic minority patients who tend to have greater
      insulin resistance than do Caucasians.

PMID- 16599349
TI  - Comparative frequency of angiographic coronary artery disease in African
      Americans and Hispanics.
AB  - BACKGROUND: African Americans and Hispanics are the two largest racial minority
      groups in the United States. Both groups have a high prevalence of cardiovascular
      disease risk factors, and African Americans have the highest mortality from
      cardiovascular disease of any racial group in the United States. Whereas a large
      body of clinical data compares African Americans and Whites or Hispanics and
      Whites with regard to coronary artery disease (CAD), limited data are available
      for such comparison between African Americans and Hispanics. METHODS AND RESULTS:
      We retrospectively reviewed the angiographic and clinical data of 480 consecutive
      patients who underwent coronary angiography for suspected CAD in an inner city
      hospital between January 1997 and December 1998 in order to ascertain the
      frequency of CAD. One hundred eighty-nine (189) African Americans and 163
      Hispanics met the inclusion criteria. The mean ages of African-American and
      Hispanic patients were similar, 56.3 +/- 10.9 years vs 55.6 +/- 11.4 years,
      respectively, P=.59. The frequency of angiographic CAD was 56.6% for African
      Americans and 54.6% for Hispanics, odds ratio [OR] 0.92, 95% confidence interval
      [CI] 0.60-1.41, P=.71). Coronary artery disease (CAD) involving the left anterior
      descending coronary artery occurred significantly more in Hispanic compared to
      African-American patients (44.8% vs 33.7%, OR 1.58, 95% CI 1.03-2.44, P=.04).
      Coronary artery disease (CAD) risk factors occurred more in Hispanics compared to
      African Americans. CONCLUSION: The frequency of angiographic CAD was not
      different for African-American and Hispanic patients (56.6% vs 54.6%, OR 0.92,
      95% CI 0.60-1.41, P=.71) even though differences were seen in CAD risk factors.

PMID- 16599350
TI  - Effects of stressful life events in young black men with high blood pressure.
AB  - OBJECTIVES: 1) To describe stressful life events as experienced by a sample of
      young Black men with high blood pressure (HBP) living in inner-city Baltimore,
      Maryland; and 2) to examine the effect of cumulative stressful life events on
      substance use, depression, and quality of life. METHODS: Data were obtained over
      48 months by interview from 210 men in an HBP management study. RESULTS:
      Stressors repeatedly occurring over time included death of family member or close
      friend (65.2%), having a new family member (32.9%), change in residence (31.4%),
      difficulty finding a job (24.3%), and fired or laid off from work (17.6%).
      Involvement with crime or legal matters was reported at least twice during the 48
      months by 33.3% of men. When a cumulative stressful life events score was
      calculated by summing the number of events experienced at 6-month points over 48
      months and tested for its relationship with the health outcomes, the findings of
      multivariate analyses revealed significant associations between cumulative life
      stressors and depression and quality of life. No significant relationship was
      found between stressful life events and substance use. CONCLUSIONS: The results
      suggest that cumulative stressful life events have a negative effect on mental
      health and quality of life in young Black men with HBP. Future study should focus
      on developing interventions to assist individuals in managing distress related to
      stressful events with necessary community resources.

PMID- 16599351
TI  - Self-reported hypertension and race among Hispanics in the National Health
      Interview Survey.
AB  - OBJECTIVES: To investigate the association between race and hypertension among
      Hispanics and non-Hispanics by using data from the National Health Interview
      Survey (NHIS), an annual survey of US households and to compare the strength of
      these associations among Hispanics and non-Hispanics. DESIGN AND METHODS:
      Analyses were limited to Hispanics and non-Hispanics 18 years of age and older
      who self-identified as White or Black/African-American during the 2000-2002 NHIS
      for a final sample of 88,453 adults including 12,083 Hispanics. Hypertension was
      self-reported during the survey interview. Covariates included in the analyses as
      potential confounders were sociodemographic characteristics and risk factors for
      hypertension. RESULTS: Hispanic Blacks had higher prevalence of self-reported
      hypertension than Hispanic Whites. Hispanic Blacks had higher odds of
      hypertension than non-Hispanic and Hispanic Whites. However, these associations
      did not achieve significance level. No difference was seen on the strength of the
      association between race and hypertension among Hispanics and non-Hispanics (OR
      1.31 vs 1.52, P interaction for race and ethnicity .91). The protective effect
      for hypertension on Hispanics had been disappearing over time (P interaction
      race/ethnicity and survey year .002). CONCLUSIONS: This study underscores that
      racial categorization could be a significant predictor of health status for
      Hispanics in our society. As time goes by, we are curious to see how embedding in
      US racial categories and assimilation into Western culture influence the life and
      health of Hispanics.

PMID- 16599352
TI  - Does weight status influence perceptions of physical activity barriers among
      African-American women?
AB  - BACKGROUND: Many African-American women fail to participate in regular physical
      activity. Weight status may influence physical activity barriers. This study
      examined the frequency and type of barriers. METHODS: Participants in this study
      were enrolled in Project EXE-L (Exercising Ladies Excel), a six-month, church
      based, randomized trial of moderate-intensity physical activity based in
      Baltimore city and county in Maryland. Participants were composed of African
      American women who attended one of the participating churches, had friends who
      were church members, or who lived in neighborhoods surrounding one of the
      churches. Individuals who were between the ages of 25 and 70 years, were not
      regularly physically active (defined as not engaging in moderate-intensity
      activity more than three times per week), and were able to participate in
      moderate-intensity activity met eligibility criteria to participate in the trial.
      Barriers to physical activity were evaluated with the Steinhardt/Dishman Barriers
      for Habitual Physical Activity Scale at baseline. RESULTS: One hundred twenty
      women were classified as normal weight (body mass index [BMI]: <25 kg/m2),
      overweight (BMI: 25-29.9 kg/m2), or obese (BMI: > or = 30 kg/m2). Obese
      participants were more likely to report "lack of motivation" as a barrier
      compared with normal-weight participants (63% vs 31%). Normal-weight and
      overweight participants were more likely to report no barriers compared with the
      obese (31%, 0%, 5%, respectively, P<.05). CONCLUSIONS: Barriers for African
      American women may vary by BMI status. By defining these unique barriers,
      effective physical activity interventions can be developed.

PMID- 16599353
TI  - Racial and ethnic differences in premature heart disease deaths in New Mexico:
      what is the role of diabetes?
AB  - Multiple-cause mortality files from 1999-2001 were obtained to describe premature
      heart disease (PHD) deaths and the role of diabetes as a contributing cause in
      heart disease (HD) mortality in American Indians, Hispanics, and non-Hispanic
      Whites in New Mexico. The proportion and rate of PHD and diabetes-related HD
      death were calculated and reported by race/ethnicity and gender. Results indicate
      that from 1999 to 2001, 24% of all deaths in New Mexico reported HD as the
      leading cause of death. Of these, 16.6% occurred in persons <65 years of age and
      were therefore classified as premature. The proportion of premature HD deaths was
      substantially higher in the American-Indian (29.2%) and Hispanic (20.8%)
      populations compared to Whites (13.7%). Furthermore, diabetes contributed to
      almost 18% of premature HD deaths in American Indians and Hispanics and to 10% of
      premature HD among Whites. These findings suggest that American Indians and
      Hispanics are disproportionately affected by premature HD death and that diabetes
      as a contributing cause is greater among these populations compared to non
      Hispanic Whites.

PMID- 16599354
TI  - Fruit and vegetable consumption of older Mexican-American women is associated
      with their acculturation level.
AB  - Little is known about the association between acculturation and fruit and
      vegetable (FV) consumption among older Mexican-American (MA) women. Environmental
      and lifestyles changes experienced by immigrants to the United States may
      markedly affect their diet and health and increase their risk for chronic
      diseases. Our objectives were to: 1) describe FV consumption by ethnicity,
      acculturation, and sociodemographic characteristics, and 2) compare effects of
      acculturation and sociodemographic variables on FV intake in a population of
      older MA and non-Hispanic White (NHW) women from the Well-Integrat-ed Screening
      and Evaluation for Women Across the Nation (WISEWOMAN) Study. This report
      examines baseline FV intake of 346 underinsured women aged 50-76 years, assessed
      through 24-hour dietary recalls. Acculturation was measured with a five-item
      Likert-type scale. Twenty percent of more acculturated MA women, 24% of less
      acculturated MA women, and 36% of White women consumed > or = 5 servings of FV
      servings per day. Fruit and vegetable (FV) intake was associated with
      acculturation, education, and smoking status. Being more acculturated was
      associated with lower consumption of FVs among MAs, while having a higher
      education and no smoking was associated with higher intakes of FV servings among
      NHWs. Public health efforts to improve the intake of FVs among MA women should be
      sensitive to their acculturation status.

PMID- 16599355
TI  - Study design of the Multicultural Community Health Assessment Trial (M-CHAT): a
      comparison of body fat distribution in four distinct populations.
AB  - OBJECTIVE: To outline the study design of the Multicultural Community Health
      Assessment Trial (M-CHAT). The purpose of the study is to compare the
      relationship between visceral adipose tissue (VAT) and total body fat in men and
      women of Aboriginal, Chinese, and South Asian origin with a similar group of men
      and women of European origin. DESIGN: A total of 200 apparently healthy men and
      women between the ages of 30 and 65 will be recruited from each of the local
      Aboriginal, Chinese, and South Asian and European communities. Within each
      sex/ethnic group, an equal representation of participants will have a body mass
      index between 18.5 to 24.9, 25 to 29.9 and >30. Each participant will undergo an
      assessment for VAT, total body fat, metabolic risk factors, physical activity,
      diet, quality of life, and sociodemographics. MAIN OUTCOME MEASURES: The primary
      outcome of this study is the relationship between VAT and total body fat in each
      of the Aboriginal, Chinese, and South Asian cohorts; this relationship will be
      compared to the European cohort after adjustment for age, sex, socioeconomic
      status, smoking status, physical activity, diet, and body mass index.
      CONCLUSIONS: This study will be the first to identify differences in body fat
      distribution in these populations. We anticipate that in populations of
      Aboriginal, Chinese, and South Asian origin, a greater proportion of total body
      fat will be deposited as VAT compared to those of European origin.

PMID- 16599356
TI  - Social correlates of the chronic stress of perceived racism among Black women.
AB  - OBJECTIVES: This study describes the perceptions of racism, passive and active
      responses to this psychosocial stressor, and it examines socioeconomic correlates
      of perceived racism in an economically diverse population of Black women.
      METHODS: The Telephone-Administered Perceived Racism Scale was administered to
      476 Black women, aged 36 to 53 years, who were randomly selected from a large
      health plan. RESULTS: The percentage of respondents who reported personally
      experiencing racism in the past five years ranged from 66% to 93%, depending on
      the specific item asked. When respondents were asked about racism toward Blacks
      as a group, perceptions of racism were even higher. For example, 68% "agreed" or
      "strongly agreed" that they had personally experienced being followed or watched
      while shopping because of their race, and 93% reported that Blacks in general
      experience this form of discrimination. Strong emotional responses to racism were
      often reported, and though more respondents (41%) reported experiencing very
      strong active emotions including anger, a substantial group (16%) reported
      experiencing very strong passive emotions such as powerlessness. Higher education
      was associated with higher perceived racism, while growing up in a middle-income
      or well-off family was associated with lower perceived racism and reduced
      likelihood of passive responses to racism. CONCLUSIONS: The high prevalence of
      perceived racism in this study population warrants further examination of this
      stressor as a potential determinant of racial health disparities. Higher
      education and income do not appear to protect women from experiencing racism and
      feeling hopeless or powerless in response.

PMID- 16599357
TI  - Black racial identity as a mediator of cardiovascular reactivity to racism in
      African-American college students.
AB  - OBJECTIVES: The purpose of the present study was to examine the ability of Black
      racial identity to mediate cardiovascular reactivity to racism. The
      Multidimensional Model of Racial Identity (MMRI), which consists of four
      dimensions, salience, centrality, regard, and ideology was used to define Black
      racial identity. The subdimensions of ideology are oppressed minority,
      nationalist, humanist, and assimilationist racial identities. DESIGN AND METHODS:
      Heart rate, cardiac output, stroke volume, and blood pressure were measured in 72
      African-American men as they viewed a videotaped scene depicting racial profiling
      and a neutral scene. We hypothesized that individuals with high levels of Black
      oriented identities (centrality, public regard, private regard, oppressed
      minority, and nationalist) would be less stressed by the racial profiling scenes
      than those low in these identities. In addition, we predicted that individuals
      with high levels of non-Black-oriented identities (assimilationist, humanist)
      would be more stressed by the racial profiling scenes than those with low levels
      of these identities. RESULTS: Private regard, humanist, and assimilationist
      racial identities were significantly associated with increased cardiovascular
      reactivity to the scenes. Specifically, private regard significantly predicted
      cardiac output and stroke volume responses to the scenes. In addition,
      assimilationist and humanist racial identities were associated with greater blood
      output and faster heart rates in response to the scenes. CONCLUSIONS: Although
      private regard (Black oriented) and assimilationist and humanist (non- Black
      oriented) racial identities showed elevated cardiovascular reactivity to the
      scenes, the underlying mechanisms of these associations may differ.

PMID- 16599358
TI  - Behavioral risk profiles for coronary heart disease among apparently healthy
      individuals of African ancestry.
AB  - OBJECTIVE: Mortality from coronary heart disease (CHD) is lower in foreign-born
      Blacks compared to their US-born counterparts. The purpose of this study was to
      determine if behavioral risk factors for CHD are different between foreign-born
      Afro Caribbeans (FBAC) and their US-born counterparts (US-born Afro Caribbean
      Americans, USBAC and African Americans, AA). DESIGN AND PARTICIPANTS: For a cross
      sectional study, 66 FBAC (31 males; 35 females) living in the United States <10
      years, 62 USBAC (30 males; 32 females), and 61 AA (30 males; 31 females) adults
      (18-40 years) were recruited. Dietary, anthropometric, physical activity,
      cigarette smoking, and alcohol consumption data were collected and analyzed. MAIN
      OUTCOME MEASURE: Risk factors for CHD. RESULTS: Significantly (P<.05) more USBAC
      (50.0%) and AA (31.0%) males consumed an unhealthy diet compared to the FBAC
      (16.7%) males. Also, significantly (P<.05) more USBAC and AA males compared to
      FBAC males were obese (20.0% and 33.3% vs 6.5%). No significant differences were
      observed between the female ethnic groups. Although less USBAC and AA males and
      females compared to FBAC males and females played sports, the differences were
      not significant. More USBAC and AA males compared to FBAC (10.0% and 3.3% vs
      0.0%) smoked cigarettes and consumed alcoholic beverages (43.3% and 63.3% vs
      16.1%). Among the female ethnic groups, only the AA smoked cigarettes.
      Significantly (P<.05) more USBAC (36.7%) and AA (33.3%) males compared to FBAC
      (3.2%) males had poorer behavioral habits, with no significant differences
      observed between the female ethnic groups. CONCLUSIONS: Our study showed
      significant differences in CHD risk behaviors among individuals of African
      decent. The FBAC participants had more favorable behaviors in preventing CHD
      compared to their US-born counterparts.

PMID- 16599359
TI  - Aerobic fitness among Caucasian, African-American, and Latino youth.
AB  - OBJECTIVE: The prevalence of obesity and related comorbidities has dramatically
      increased in the pediatric population in recent years, and youth from ethnic
      minorities appear to be disproportionately affected. Although several factors
      play a role in these ethnic health disparities, evidence suggests fitness may
      also be an important mediator of disease risk in children. Therefore, the purpose
      of the present investigation was to compare aerobic fitness (VO2peak) in healthy
      Caucasian (C), African-American (AA), and Latino (L) youth and to evaluate
      differences after controlling for gender, maturational stage, and body
      composition. MEASURES: Seventy-three healthy boys and girls [C (n=18), AA (n=19),
      and L (n=36)] aged 7-14 years participated in the study. VO2peak was evaluated
      using an all-out, progressive treadmill protocol, total body composition was
      estimated via dual-energy x-ray absorptiometry, and ethnicity was determined via
      parental questionnaire. RESULTS: VO2peak relative to total body mass (mL/kg/min)
      was significantly lower in Latinos compared to either Caucasian or African
      American children. Further, after controlling for gender, maturational stage, and
      body composition, L (1.68 +/- 0.05 L/min) and AA (1.57 +/- 0.05 L/min) youth had
      significantly lower VO2peak compared to C (1.84 +/- 0.04 L/ min; P<.05) children.
      CONCLUSION: These results suggest that Latino and African-American children have
      lower aerobic fitness levels than Caucasian children and this effect is
      independent of gender, maturation, and body composition.

PMID- 16599360
TI  - Disparities in diabetes-related hospitalizations: relationship of age, sex, and
      race/ethnicity with hospital discharges, lengths of stay, and direct inpatient
      charges.
AB  - OBJECTIVE: To identify any differences in hospitalization rates of diabetes
      patients by age, sex, or race/ethnicity. DESIGN: A cross-sectional study of
      Georgia hospital discharge data between 1998 and 2001. PATIENTS/PARTICIPANTS:
      Patients with a principal discharge diagnosis of diabetes. MAIN OUTCOME MEASURES:
      Adjusted hospitalization data (discharge rates, length of stay, direct charges)
      reported as standardized rates per 10,000 person-years, standardized rate
      differences, and standardized rate ratios, compared by age, sex, and
      race/ethnicity. RESULTS: Diabetes was the principal diagnosis in 50,301
      discharges (average age, 51 years; length of stay, 5.1 days; median total charge,
      $5893). Persons > or = 60 years old had higher discharge rates, longer stays, and
      higher charges than persons 18-29 years old. Women had fewer hospitalizations,
      shorter stays, and lower charges than men. Non-Hispanic Blacks had more than
      three times as many hospitalizations, markedly longer stays, and higher charges
      than non-Hispanic Whites. Hispanics with diabetes had lower hospitalization
      rates, shorter stays, and lower charges than Whites. CONCLUSIONS: Differences by
      age, sex, and race/ethnicity in hospital discharge rates, lengths of stay, and
      charges exist for diabetes inpatients. Further study should examine potential
      causes (severity of disease, comorbidity, and differential access to preventive
      care) of these disparities.

PMID- 16599361
TI  - Quality improvement for prevention of cardiovascular disease and stroke in an
      academic family medicine center: do racial differences in outcome exist?
AB  - OBJECTIVES: We evaluated whether a one-year, multifaceted quality improvement
      intervention improved adherence to 13 clinical guidelines for lipid screening,
      hypertension management, and diabetes management among White and African-American
      adult patients. SETTING: An academic family medicine center. PARTICIPANTS: Six
      faculty physicians and a clinical pharmacist participated between July 1, 2002,
      and June 30, 2003. Data from 2860 patients' electronic medical records were
      abstracted. INTERVENTIONS: Performance reports and lists of patients eligible for
      each guideline measure were generated. Interventions targeted patients who needed
      improvement. Statistical analyses used generalized estimating equations to
      determine the intervention effect. RESULTS: Significant improvements occurred in
      blood pressure control for all adults (OR= 1.44) and those with hypertension
      (OR=1.82), measures of total cholesterol (OR=1.10) and high-density lipoprotein
      cholesterol (OR= 1.27) for all patients, and measure of low-density lipoprotein
      cholesterol (OR=2.01) and blood pressure control (OR=1.71) for patients with
      diabetes mellitus. Significant decline was seen in measures of blood pressure for
      all patients (OR=.60). After adjusting for patient demographic factors, provider
      variability, and comorbidities, race was not associated with the change observed
      in any of the measures from baseline to follow-up. CONCLUSIONS: Even though a
      multifaceted intervention can improve process of care measures for Whites and
      African Americans, further studies are needed to improve outcome measures,
      especially in African Americans.

PMID- 16599362
TI  - Addressing cardiovascular disparities through community interventions.
AB  - OBJECTIVES: To identify the components and impact of intervention programs aimed
      at reducing cardiovascular disparities. METHODS: A MEDLINE literature search with
      key words "cardiovascular" and "African American" was conducted, and all
      documented interventions targeted at reducing racial disparities were selected
      for review. We identified the type of intervention, the populations targeted, the
      length of intervention, and its impact. Articles that documented scientific
      evidence and some case reports were reviewed. RESULTS: Existing studies widely
      document cardiovascular disparities as they pertain to structure, process, and
      outcomes. Other factors affecting disparities pertain to patient, physician,
      system, or treatment factors. Documented programs tend to focus on lifestyle risk
      factors and attitudes toward those risk factors. The timelines in the studies are
      relatively short and do not allow for recording clinical endpoints. Most of the
      studies do not hinge on comprehensive community support, and they lack a
      sustainability component. CONCLUSIONS: The impact of programs has been short
      lived, which points to the need for sustainability programs possibly through
      community partnerships.

PMID- 16599363
TI  - Barriers to care and control of high blood pressure in Korean-American elderly.
AB  - OBJECTIVES: To identify barriers to achieving optimal management of high blood
      pressure (HBP) among hypertensive Korean-American elderly (KAE). METHODS: This
      study used data on a subsample of 146 hypertensive KAE from a total of 205 KAE in
      Maryland who participated in a cardiovascular health assessment study. The study
      group consisted of 56 males and 90 females with a mean age of 69.8 +/- 6.6 years.
      The PRECEDE-PROCEED model guided selection of study variables. RESULTS: Many KAE
      with HBP had no regular HBP care (66%) and did not achieve HBP control (92.5% of
      KAE with HBP and 77.6% of KAE on HBP medications). Lack of health insurance
      emerged as a strong barrier to receiving adequate HBP care. Other barriers to HBP
      care included not having a Korean doctor and not having a regular medical
      checkup. While 22.4% of KAE on HBP medication had controlled blood pressure (BP),
      those with more visits to traditional Asian medicine doctors were less likely to
      have achieved HBP control. CONCLUSIONS: The study unveils some of the multilevel
      barriers to care and control of HBP uniquely experienced by KAE and suggests the
      need for developing interventions to assist KAE in managing HBP.

PMID- 16599364
TI  - Effect of race category redefinition on hypertension and hypercholesterolemia
      prevalence in the behavioral risk factor surveillance system, 1999 and 2001.
AB  - Race information in the United States is used to identify populations at risk for
      cardiovascular disease (CVD) or associated risk factors. Behavioral Risk Factor
      Surveillance System data from 1999 and 2001 were used to examine shifts in racial
      distributions and CVD risk factors after a multiracial category was added in
      2001. We compared age-adjusted, weighted, race-specific prevalence estimates of
      self-reported high blood pressure (HBP) and high blood cholesterol (HBC) from
      1999 and 2001 with descriptive statistics and 95% confidence intervals. The
      proportion of non-Hispanic Whites decreased significantly after the multiracial
      category was added. Overall, the prevalence of HBC did not significantly change,
      but HBP increased significantly, from 24.2% in 1999 to 25.6% in 2001 (P<.05).
      Among racial groups, only non-Hispanic Whites showed a statistically significant
      increase in HBP prevalence from 23.1% to 24.4% (P<.05); however, larger
      percentage increases in HBP were seen among non-Hispanic Asian/Pacific Islanders
      (3.5%) and non-Hispanic Blacks (1.6%). Among non-Hispanic Whites, when combining
      multiracial respondents whose preferred single race was non-Hispanic White, the
      prevalence of HBP was significantly higher in 2001 than in 1999. The race
      specific prevalence of HBP and HBC was virtually unchanged, whether or not
      multiracial respondents were included in prevalence estimates. Observed HBP
      increases for non-Hispanic Whites were not caused by the addition of a
      multiracial category. In 2001, multiracial respondents had the second highest
      prevalence of HBP after non-Hispanic Blacks. To promote heart health, we must
      focus on the needs of this emerging multiracial group and on groups with
      increasing rates of HBP.

PMID- 16599365
TI  - Racial analyses of longer-stay nursing home residents with multiple sclerosis.
AB  - OBJECTIVES: Compare profiles of African Americans with multiple sclerosis (MS) to
      White residents with MS one year after admission to a nursing facility. METHODS:
      We used all admission assessments recorded in the national Minimum Data Set (MDS)
      from 1999 to 2001 as well as all MDS annual assessments recorded from 2000 to
      2002. We matched admission assessments with first annual assessment for 3632
      White residents with MS and 461 African-American residents with MS. RESULTS:
      African Americans with MS were admitted at a significantly younger age and with
      more aid to daily living (ADL) dependence and cognitive dysfunction than Whites
      with MS one year after admission. Despite significantly poorer physical
      performance, cognitive function, and more medical comorbidities, African
      Americans with MS did not receive significantly more therapies or medications
      than White residents with MS after one year in the facility. CONCLUSIONS: Basic
      differences in MS expression and progression in African Americans appear to have
      to do with both genetic and environmental factors. Further study will help to
      clarify the reasons for these differences.

PMID- 16599366
TI  - Intergenerational birth weights among the direct female descendants of US-born
      and Mexican-born Mexican-American women in Illinois: an exploratory study.
AB  - OBJECTIVE: To explore the intergenerational birth-weight patterns of the direct
      female descendants of Mexican-American women. DESIGN: This is a population-based
      study. METHODS: Stratified analyses were performed on a transgenerational dataset
      of 1956-1975 and 1989-1991 Illinois computerized vital records of Mexican
      American infants. RESULTS: Among the descendants of generation 1 US-born Mexican
      American women (n=1,940), generation 3 females had a birth weight equivalent to
      that of their generation 2 mothers, (3294 g vs 3283 g); generation 3 infants with
      unmarried mothers had a birth weight 121 g less than that of generation 2 infants
      born to unmarried mothers (3163 g vs 3284 g, P<.01); and generation 3 female
      infants born to teenaged women had a birth weight 70 g less than that of their
      generation 2 mothers who were born to teenaged women (3178 g vs 3248 g, P<.01).
      Among the descendants of generation 1 Mexican-born women (n=1,017), generation 3
      females had a birth weight equivalent to that of their generation 2 mothers (3335
      g vs 3363 g); generation 3 infants with teenaged mothers had a birth weight 108 g
      less than that of generation 2 infants with teenaged mothers (3264 g vs 3372 g,
      P<.01). CONCLUSIONS: An intergenerational rise in birth weight does not occur
      among the direct female descendants of Mexican-American women.

PMID- 16599368
TI  - Advancing maternal age and infant birth weight among urban African Americans: the
      effect of neighborhood poverty.
AB  - OBJECTIVE: This study sought to determine whether neighborhood poverty modifies
      the relationship between maternal age and infant birth weight among urban African
      Americans. DESIGN: Stratified analyses were performed on the vital records of
      African Americans born in Chicago by means of 1992-1995 computerized birth file
      with appended 1990 US Census income and 1995 Chicago Department of Public Health
      data. Four neighborhood-level variables (low median family income, high rates of
      unemployment, homicide, and lead poisoning) were analyzed. SETTING: This is a
      population-based study. RESULTS: Twenty-one percent (n=21,811) of women resided
      in nonimpoverished neighborhoods (zero ecologic risk factors); 23% (n=24,914) of
      women lived in extremely impoverished neighborhoods (four ecologic risk factors).
      In nonimpoverished neighborhoods, 30-34 year old women had a moderately low birth
      weight (1500-2499 g) rate of 13.9% compared to 10.3% for women aged 20-24 years;
      risk difference (95% confidence interval [CI])=3.5 (2.2-4.6). In contrast,
      extremely impoverished women aged 30-34 years had a moderately low birth weight
      rate of 19.8% compared to 11.8% for women aged 20-24 years; risk difference (95%
      CI)=7.7 (6.1-9.3). This trend persisted among women who received early prenatal
      care and were primagravids or of low parity. Neighborhood poverty did not modify
      the association of advancing maternal age and the risk of very low birth weight
      (<1500 g). CONCLUSIONS: Neighborhood poverty accelerates the rise in moderately
      low birth weight but not very low birth weight; rates were associated with
      advancing maternal age among urban African Americans.

PMID- 16599367
TI  - Relations of black mothers' and daughters' body fatness, physical activity
      beliefs and behavior.
AB  - OBJECTIVES: 1) Examine the association between Black mothers' and daughters' body
      fatness, physical activity (PA) beliefs and levels of PA, and daughters' PA
      behavior; 2) determine whether family sociodemographic factors influence these
      relationships. DESIGN AND SETTING: Cross-sectional; Black girls recruited from
      elementary schools in a low socioeconomic area. Data collected at the Georgia
      Prevention Institute. PARTICIPANTS: 133 Black girls (8-12 years of age) and their
      mothers (24-66 years of age). ANALYSES: Spearman correlations, regressions.
      OUTCOME MEASURES: Body mass index (BMI) as a measure of body fatness. Moderate
      and vigorous PA collected from a 7-d recall. Beliefs about PA collected from
      questionnaires. RESULTS: There was a positive relation between mothers' and
      daughters' BMI (rs=0.34, P<.0001). Mothers' and daughters' PA beliefs were
      positive but not significantly related. A significant inverse relation was seen
      between vigorous PA (rs=-0.16, P<.05); and a non-significant correlation between
      moderate PA (rs=0.05). Mothers' body fatness, PA beliefs and behavior did not
      predict daughters' PA. The BMI association was stronger when spouse lived in
      household (P<.01). Daughters' BMI was lower (P<.05) and intent to be active
      higher (P<.05) when more people lived in the household. Family income accentuated
      the relation of mothers' belief in the usefulness of PA and daughters' PA
      physical outcomes beliefs (P=.1). Mothers' age and education had no significant
      influence on daughters' PA beliefs and behaviors. CONCLUSION: Mothers and
      daughters believed PA to have beneficial outcomes. Mothers' body fatness, PA
      beliefs and behaviors were not associated with daughters' PA. Family income and
      structure appeared to influence these relationships.

PMID- 16599369
TI  - The relationship between maternal child-feeding practices and overweight in Hmong
      preschool children.
AB  - OBJECTIVE: Maternal child-feeding practices have been linked to overweight in
      several studies. Overweight is a prevalent condition in Hmong preschool children
      in the United States, therefore, the purpose of this study was to determine
      whether maternal child-feeding attitudes and practices were associated with
      overweight in Hmong preschool children. DESIGN: The Child-Feeding Questionnaire
      (CFQ) was revised and administered to Hmong mothers with normal-weight and
      overweight children. SETTING: Women, Infant, and Children Supplemental Food
      Program (WIC) clinics and community centers in the Minneapolis-St. Paul
      metropolitan area. PARTICIPANTS: Hmong mothers of normal-weight (n=45) and
      overweight (n=35) children. MAIN OUTCOME MEASURES: Relationships between maternal
      perceptions of child's weight, practices in child feeding, including monitoring,
      restriction, and pressure to eat, and overweight status in children. RESULTS: No
      association was found between maternal attitudes and practices in child feeding
      and body mass index (BMI) of the child except for mother's perception of her
      child's weight. Mother's perception of her child's weight was also associated
      with maternal restriction of certain foods. Mother's education and children's
      weight status were weakly positively associated. Mothers with more education
      tended to be younger and to work outside the home. CONCLUSION: The lack of a
      relationship between maternal child-feeding practices and children's weight
      status may be due to factors such as mother's education, role of other
      caregivers, and cultural factors.

PMID- 16599370
TI  - Predictors of early postpartum vitamin use among women of Mexican origin:
      implications for healthcare provider recommendations.
AB  - OBJECTIVE: High parity and short birth intervals among Hispanic women may deplete
      their folic-acid levels and place them at risk for neural tube defects (NTDs).
      The purposes of this study were to evaluate factors associated with multivitamin
      supplementation rates during the early (one to six weeks) postpartum period among
      Mexican-origin women and present their implications in preventing NTDs in
      subsequent pregnancies. DESIGN: A cross-sectional study was conducted among
      Hispanic mothers attending women, infant, and children (WIC) clinics in El Paso,
      Texas. Information was ascertained via interview on regular multivitamin use, and
      independent variables including sociodemographic characteristics, multivitamin
      knowledge, obstetric and health history, and birth control and infant feeding
      methods. RESULTS: Only 66% of 329 mothers took postpartum multivitamins.
      Multivitamin consumption declined by 29% for each postpartum week (P=.0003).
      Adjusted odds ratios indicated positive associations between multivitamin
      supplementation and prenatal care exclusively in the United States (P=.007),
      breastfeeding (P=.071), preconceptional (P=.005) and prenatal multivitamin use
      (P=.0002), and multivitamin recommendation from a healthcare provider (P < or =
      .0001). The majority of 247 women with multivitamin counsel (59%) were told to
      finish prenatal vitamins or to continue use while breastfeeding. Smokers were
      less likely to take multivitamins than nonsmokers (P=.007). CONCLUSIONS: A
      provider recommendation highly motivates early postpartum women to consume
      multivitamins. Since most women have more than one child, this period likely
      represents an interpregnancy interval and is an opportune time to educate and
      encourage women to take multivitamins. This simple and inexpensive measure could
      prevent birth defects in future pregnancies.

PMID- 16599371
TI  - Associations of nationality and race with nutritional status during
      perimenopause: implications for public health practice.
AB  - OBJECTIVE: To examine associations of nationality and race with anthropometry,
      self-reported nutrient intakes, health history, and socioeconomic status (SES) of
      perimenopausal (age 40-55 years) Floridians. DESIGN: Interviewer conducted cross
      sectional survey. SETTING: South Florida, 2000-2001. PARTICIPANTS: Convenience
      sample of 109 Black (Caribbean [n=31] and African-American [n=251), and White
      (n=53) women with intact ovaries and uteri. MAIN OUTCOME MEASURES: Nutrient
      intakes and anthropometry. RESULTS: Both races had similar mean age, education,
      SES, reported heavy menses, and physician-diagnosed iron deficiency anemia.
      Dietary reference intakes (DRIs) were unmet for calcium (67%) and iron (35%) and
      exceeded for energy (28%). A decade of decreased milk (61%) and red meat (69%)
      consumption, key micronutrient sources, was reported. Significantly more Blacks
      exceeded anthropometric recommendations (P=.01); more African Americans exceeded
      energy DRIs even after controlling for body mass index (P=.006). More Whites
      exceeded calcium DRIs (P=.04) and reported self-diagnosed depression (P=.001).
      More Caribbean-born (P<.05) met fat, saturated fat, carbohydrate, and fiber
      recommendations. CONCLUSION: Reported suboptimal iron and calcium intakes coupled
      with bone demineralization and heavier menses, characteristic of perimenopause,
      could heighten osteoporosis and anemia risks. Reports that more Whites were
      depressed and more Caribbean-born persons met dietary recommendations, even
      though anthropometrics and BMI-adjusted energy intakes among Blacks exceeded
      recommendations, have possible public health implications. As more "baby-boomers"
      reach this age, findings highlight the need for culturally appropriate
      interventions, eg, nutrition education that emphasizes relationships between
      nutrient and energy needs and the composition of foods consumed by various
      ethnicities.

PMID- 16599372
TI  - Potential differences in breast cancer risk factors based on CYP1A1 MspI and
      African-American-specific genotypes.
AB  - OBJECTIVES: Recent studies show that an Mspl polymorphism in the 3'-noncoding
      region of the CYP1A1 gene is associated with breast cancer in African-American
      women but not in Caucasian women. In addition, an African-American-specific (AAS)
      polymorphism is located in intron 7 of this gene. We hypothesized that the AAS
      polymorphism may partially account for this race-specific association and that
      different environmental risk factor profiles are a function of genotype status.
      We studied both CYP1A1 polymorphisms to determine if African-American women with
      these variants have breast cancer risk factor profiles that are different from
      those of other African-American women. METHODS: A case-control analysis was
      conducted. Cases were 304 African-American patients pathologically diagnosed with
      breast cancer from 1995 to 1998 who lived in three Tennessee counties. Controls
      were 305 African-American women without breast cancer, selected through random
      digit dialing and frequency matched to cases by age and county. Information on
      risk factors was collected through telephone interviews. Tumor tissue samples
      were collected for CYP1A1 genotyping. There were 215 and 188 cases with the Mspl
      and AAS polymorphisms measured respectively. RESULTS: Our study results suggest
      that some risk factors for breast cancer are dependent upon CYP1A1 genotype.
      Specifically, low intakes of folate, methionine, vitamin C, and vitamin E appear
      to increase the risk of breast cancer in individuals with the AAS variant: the
      odds ratio (OR) estimates and 95% confidence intervals were 2.10 and 0.99-4.44
      for folate, 1.96 and 0.91-4.23 for methionine, 2.13 and 1.00-4.53 for vitamin C,
      and 2.43 and 1.12-5.25 for vitamin E. Such associations are stronger for tumors
      with both AAS and MspI polymorphisms: the OR estimates increased to >6.00 for all
      these variables except for vitamin C. CONCLUSIONS: This study found that methyl
      deficient diets and antioxidant vitamins may be related to the risk of breast
      cancer as a function of the Mspl and AAS genotpyes. Our results are preliminary
      because of a small number of cases with polymorphisms at both sites, but they
      indicate the need for large-scale epidemiologic studies of both African-American
      and Caucasian women that include genotype information from controls with more
      detailed information on risk factors.

PMID- 16599373
TI  - The future of women of minority race/ethnicity in breast cancer chemoprevention
      therapy.
AB  - Women of minority race/ethnicity have been underrepresented in United States
      based breast cancer chemoprevention trials. Searches of Medline between 1966 and
      2004 were done with priority given to recent reports (1996-2004), and references
      from bibliographies of relevant articles. Large chemoprevention trials have
      reported significant breast cancer risk reduction and increased risk of serious
      adverse events in tamoxifen-treated, high-risk women, which illustrates the need
      to carefully assess the risk/benefits of this therapy. The mathematical model
      used for this purpose in the United States-based trials has resulted in the
      inclusion of very few women of minority racial/ethnic backgrounds. The continued
      use of this risk assessment that has not been adequately validated for its
      usefulness in non-Caucasian populations, should be reviewed, especially given
      that adequate alternative nonmathematical models exist. Current and future
      chemoprevention trials should also use nonmathematical selection criteria to
      ensure that eligible underrepresented minorities are adequately included in these
      trials.

PMID- 16599374
TI  - Papanicolaou testing among Native American and Hispanic populations.
AB  - OBJECTIVE: The purpose of this study was to explore the perceptions and knowledge
      of, and access to, Papanicolaou (Pap) testing among Hispanic and Native-American
      women. DESIGN: A cross-sectional descriptive study was conducted by surveying
      Hispanic and Native-American women. The survey was developed with the constructs
      of the Preventive Health Model and was designed to assess background
      characteristics, representation factors, social influence factors, and program
      factors among Hispanic and Native-American females. PARTICIPANTS: Hispanic (n=48)
      and Native-American (n=68) women aged 18 to 89 years. SETTING: The surveys were
      distributed in several community health event sites throughout the Kansas City
      Metropolitan Area. MAIN OUTCOME MEASURES: The primary response (dependant)
      variables include knowledge, cervical screening intentions, and perceptions
      regarding the use of the Pap test. RESULTS: Most of the women surveyed (97%) had
      heard about Pap testing and reported having had a Pap test. Abnormal Pap test
      results were reported by 36% of the respondents. Acculturation and less income
      were significant factors in whether respondents could afford a Pap test, had
      health insurance, had a regular healthcare provider, and worried that a Pap test
      would uncover cervical cancer. Income was additionally related to having a doctor
      recommend Pap testing, the ability to get to the doctors' office during office
      hours, and fear of a cervical cancer diagnosis. CONCLUSION: Acculturation (or
      language) and income were determinants of Pap screening behavior among Native
      American and Hispanic women.

PMID- 16599375
TI  - Disparities in colorectal cancer screening: a guideline-based analysis of
      adherence.
AB  - PURPOSE: This study's primary objective was to describe colorectal cancer (CRC)
      screening disparities using a guideline-derived definition of CRC screening
      adherence while controlling for confounding factors associated with CRC
      screening. METHODS: This secondary data analysis of the 2000 National Health
      Interview Survey (NHIS) included 12,677 individuals age > or = 50 years. The
      primary outcome assessed was adherence to CRC screening guidelines, defined as a
      sigmoidoscopy or proctoscopy within the last five years, colonoscopy within the
      last 10 years, or home fecal occult blood test within the last 12 months. Age,
      race/ethnicity, gender, physical disability, household income, insurance status,
      education level, marriage status, rural or urban geographic area, and family
      history of CRC were analyzed as covariates in a logistic regression model. We
      assessed the association between these sociodemographic variables and receipt of
      physician recommendation for CRC screening among those respondents not adherent
      to CRC screening recommendations. RESULTS: In the multivariate model, the odds
      for being adherent with current CRC screening recommendations were lower for
      Hispanics (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.59-0.86) and
      African Americans (OR 0.82, 95% CI 0.71-0.95) than for Whites. Residents of urban
      areas had higher odds (OR 1.19, 95% CI 1.06-1.34) of being up-to-date than rural
      residents. Among subjects who were not up-to-date with CRC screening, similar
      disparities were noted in receipt of physician recommendation for CRC screening.
      CONCLUSIONS: Certain groups are at increased risk of not receiving CRC screening
      or recommendations for screening from their physicians. Interventions to reduce
      these disparities should be an integral part of overall efforts to improve CRC
      prevention and control.

PMID- 16599376
TI  - An evaluation of the knowledge, attitudes, and beliefs of African-American men
      and their female significant others regarding prostate cancer screening.
AB  - This study examines the knowledge, attitudes, and beliefs of African-American men
      and their female significant others regarding prostate cancer screening. Study
      flyers and a television interview were used to recruit participants into the
      study that took place in Harrisburg, Pennsylvania. Six focus groups were
      conducted: four with African-American men and two with female significant others.
      A total of 32 people participated in the study. The groups expressed multiple
      apprehensions toward prostate cancer screening, including feelings of
      vulnerability, compromised manhood, and discomfort. They also shared motivators
      for screening, including female significant others, physician recommendation,
      early education, and church influence.

PMID- 16599377
TI  - Adolescent nicotine metabolism: ethnoracial differences among dependent smokers.
AB  - Variations in nicotine metabolism are thought to contribute to differences in
      cigarette consumption between African Americans and Caucasian adult smokers. To
      investigate the potential mechanism of previously documented lower smoking rates
      among African-American adolescent smokers seeking cessation treatment, we
      measured nicotine metabolite ratios as markers of the metabolic disposition of
      nicotine, which is generally considered to be under the influence of cytochrome
      P450 (CYP) 2A6. Plasma ratios of trans-3'-hydroxycotinine (3HC) to cotinine (COT)
      were examined in 92 cessation treatment-seeking adolescents (mean age 15.2 years,
      standard deviation [SD] 1.3, 69% female, 31% African American, mean Fagerstrom
      Test for Nicotine Dependence [FTND] 6.5, SD 1.6, mean years smoked 2.6, SD 1.6).
      Groups were similar in age, gender distribution, and mean FTND score. Analysis
      with independent t tests revealed significantly lower number of cigarettes per
      day (CPD) (15.1, SD 7.6 vs 19.6, SD 8.0, P=.013) and nicotine metabolite ratios
      (0.27, SD 0.15 vs 0.35, SD 0.16, P=.026) in African-American compared to
      Caucasian adolescent smokers. Consistent with metabolic variation, mean COT/CPD
      ratio was significantly higher in African-American compared to Caucasian
      adolescents. Results remained statistically significant when comparing menthol
      smokers by ethnicity. These findings are consistent with those found among adult
      smokers and provide a putative mechanism for reported ethnoracial differences in
      adolescent cigarette consumption. Our results underscore the need for measures
      independent of consumption for determining degree of nicotine dependence and
      treatment selection across ethnicities, even among youths.

PMID- 16599378
TI  - Age, race, and repeated prostate-specific antigen (PSA) test use in the National
      Health Interview Survey.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer death in
      American men. Prostate-specific antigen (PSA) test use was examined in US men
      aged > or = 40 years to clarify the relationship with age and race. METHODS: The
      National Health Interview Survey (2000) collected information about PSA test use
      in a representative sample of the US population. This study examined whether men
      reported having had three or more PSA tests within the past five years by age and
      race subgroups. RESULTS: Prostate-specific antigen (PSA) test use rates were
      lowest in men aged 40-49 and highest in men aged 65-79. Receipt of three or more
      PSA tests within the past five years varied by age and race. Use was higher for
      African-American men, compared with White men aged 40-49; similar for African
      American and White men aged 50-64; higher for White than African-American men
      aged 65-79; and similar for African-American and White men aged > or = 80.
      CONCLUSION: The PSA test use patterns showed variation by age and race subgroups,
      and these patterns are better understood when examining both variables at the
      same time.

PMID- 16599379
TI  - "Heat in their intestine": colorectal cancer prevention beliefs among older
      Chinese Americans.
AB  - OBJECTIVE: Data regarding disease prevention behaviors among Asian-American
      populations are limited. This study explored the beliefs of older Chinese
      Americans toward colorectal cancer screening modalities, including fecal occult
      blood testing (FOBT). DESIGN AND PARTICIPANTS: We conducted 30 semistructured,
      open-ended, qualitative interviews in Mandarin and Cantonese, focusing on
      colorectal cancer prevention and health-seeking behavior. Participants were
      Chinese patients 50-79 years of age recruited from a community clinic in Seattle,
      Washington. RESULTS: When asked about colorectal cancer prevention, interviewees
      discussed such concepts as maintenance of positive energy (qi) and spirit (jing
      shen) and moderation of exercise and diet. Until prompted, participants did not
      discuss FOBT. Interviewees believed that colorectal cancer was caused by diets
      high in foods with "heat" (huo qi) or by intestinal toxins from frequent
      constipation. Participants presumed that FOBT is unnecessary in the absence of
      symptoms. CONCLUSIONS: Patients in our study expressed beliefs about health
      promotion and causes of colorectal cancer that differed from Western biomedical
      concepts. Failure to recognize these different beliefs may create inadvertent
      confusion among elderly Chinese-American patients. Health promotion programs to
      increase colorectal cancer screening must incorporate these concepts to improve
      cultural relevance among Chinese-American patients.

PMID- 16599380
TI  - Barriers and facilitators of colorectal cancer screening among Mid-Atlantic
      Latinos: focus group findings.
AB  - OBJECTIVE: To examine patient and provider barriers and facilitators of
      colorectal cancer (CRC) screening among mid-Atlantic Latinos seeking care at
      urban primary care clinics and describe implications for the design of
      interventions in primary care. DESIGN AND METHOD: Nine focus groups were
      conducted with 70 Latino patients and 27 primary care providers. Content analysis
      of focus group transcripts was performed using established qualitative
      techniques. RESULTS: Comments on CRC screening fell into 10 content areas:
      primary care site or provider characteristics (25% patient/21% provider
      comments); knowledge (18% patient/12% provider comments); cost/insurance coverage
      (10%/25%); attitudes (14%/7%); ordering of priorities (10%/11%); language
      (12%/7%); procedural issues regarding screenings (8%/10%); discrimination
      (2%/1%); and issues related to being a new immigrant (.2%/6%). Patient lack of
      understanding of the screening test procedures, inadequate knowledge about
      colorectal cancer, inadequate numbers of Spanish-speaking providers, and the cost
      of screening were most often cited as barriers by patients. Both providers and
      patients repeatedly mentioned the lack of funding and referral sources for
      colonoscopy as a key barrier to performing screening, even with lower-cost fecal
      occult blood tests, as colonoscopy follow-up would not be available. Patients
      favored receiving CRC screening recommendations from their usual continuity
      physician, but were open to receiving information on test procedures and
      indications from a Spanish-speaking health educator. CONCLUSIONS: Efforts to
      improve funding and availability of colonoscopy for low-income persons could
      proceed in tandem with linguistically and culturally appropriate clinic-based
      efforts to improve CRC screening among Latinos.

PMID- 16599381
TI  - Ethnic differences in hiv disease progression: a comparison of Asian/Pacific
      Islanders and Whites living in Hawaii.
AB  - OBJECTIVE: To characterize the association of demographic factors with the
      relative hazards (RH) of developing AIDS or death among HIV-infected individuals
      of Asian/Pacific Islander (API) ethnicity and Whites. DESIGN: Cohort study
      SETTING: Hawaii State Health Department database of HIV-infected individuals
      PATIENTS OR PARTICIPANTS: Hawaii Sero-Positivity and Medical Management (HSPAMM)
      program participants from January 1989 to November 2002 INTERVENTIONS: None MAIN
      OUTCOME MEASURES: Differences in the time to develop AIDS or death among HIV
      infected individuals who reported being on highly active antiretroviral treatment
      (HAART) were examined by ethnicity, income, and CD4+ cell counts at HAART
      initiation by using Kaplan-Meier survival analysis and Cox proportional hazard
      analyses. RESULTS: The study was based on 516 HIV-infected individuals, who were
      primarily White (61.0%) and API (21.7%). Whites had a significantly higher CD4+
      cell count (P<.01) and income (P<.01) than APIs at enrollment into HSPAMM. Lower
      income levels and CD4+ cell counts at HAART initiation were strongly associated
      with an increased RH of developing AIDS or dying. Despite having significantly
      lower incomes and CD4+ cell counts at enrollment, individuals of API ethnicity do
      not have an increased RH of developing the outcomes compared to Whites.
      CONCLUSION: Lower income and CD4+ cell counts at HAART initiation significantly
      increased the RH of developing AIDS or dying among HIV-infected individuals.
      Asian/Pacific Islander (API) ethnicity was not a predictor of developing AIDS or
      dying.

PMID- 16599382
TI  - Antibiotics and upper respiratory infections: the impact of Asian and Pacific
      Island ethnicity on knowledge, perceived need, and use.
AB  - The threat of microbial resistance to antibiotics grows increasingly serious each
      year. Despite the severity of the problem, little is known about ways that
      ethnicity and culture influence antibiotic knowledge, attitudes, and use. Based
      on a random sample of residents from a multicultural metropolitan county in the
      western United States, this study finds that Filipinos have lower levels of
      antibiotic knowledge, express higher perceived need, and report more frequent
      use. Whites in this sample are at the opposite end on all of these measures;
      other Asian Americans and Hawaiians/Pacific Islanders are in between. The results
      also suggest that preference for a "paternalistic" interaction/decision-making
      style between Filipino patients and their physicians may increase the challenge
      of designing an effective intervention promoting appropriate antibiotic use; a
      social marketing approach may be one possible alternative. Implications and
      future research directions are discussed for other multicultural urban
      environments that experience inappropriate use of antibiotics.

PMID- 16599384
TI  - The influence of religion on organ donation and transplantation among the Black
      Caribbean and Black African population--a pilot study in the United Kingdom.
AB  - Currently the demand for transplant organs, particularly kidneys, far outstrips
      the supply in the United Kingdom. This problem is particularly severe for the
      Black African and Black Caribbean populations who have a higher predisposition to
      end-stage renal failure. Several commentators have suggested that religious and
      cultural traditions may be the major determinant preventing Black Africans and
      Black Caribbeans from donating organs. An exploratory qualitative study using
      focus groups was undertaken with the aim of examining the influence of religion,
      among other things, on the extent and direction of public attitudes toward organ
      donation in a cross-section of the Black African and Black Caribbean populations
      in Lambeth, Southwark, and Lewisham. In almost every focus group, religion and
      faith were expressed as issues that could prevent Black people from becoming
      organ donors. Organ donation was debated with caution on the basis of how their
      religious experience had influenced them. This finding suggests that the church
      and faith leaders could play a greater role in raising awareness of organ
      donation in these communities. Religious leaders can reach large numbers of
      people in a short space of time and will assist members of any group to
      understand more fully the religious stance on the subject matter. This education,
      in the long term, may lead to more people becoming organ donors.

PMID- 16599383
TI  - Fruit and vegetable access differs by community racial composition and
      socioeconomic position in Detroit, Michigan.
AB  - OBJECTIVE: To compare the availability, selection, quality, and price of fresh
      fruit and vegetables at food stores in four Detroit-area communities: 1)
      predominately African-American, low socioeconomic position (SEP); 2) racially
      heterogeneous, low SEP; 3) predominately African-American, middle SEP; and 4)
      racially heterogeneous, middle SEP. DESIGN: Cross-sectional observational survey,
      conducted fall 2002. SETTING: Detroit, Michigan SAMPLE: Overall, 304 food stores
      located in the four communities were evaluated: chain grocery, large independent
      grocery, "mom-and-pop" grocery, specialty (meat, fruit and vegetable markets),
      convenience without gasoline, and liquor stores. MAIN OUTCOME MEASURES:
      Availability was indicated by whether a store carried fresh fruit or vegetables,
      selection was based on a count of 80 fruit and vegetables, quality was evaluated
      according to USDA guidelines for a subset of 20 fruit and vegetables, and price
      was assessed for 20 fruit and vegetables by using the lowest-cost method.
      RESULTS: Mean quality of fresh produce was significantly lower in the
      predominately African-American, low-SEP community than in the racially
      heterogeneous, middle-SEP community. Differences in the types of stores present
      only partially explained this quality differential. The predominately African
      American, low-SEP community had more than four times more liquor stores and fewer
      grocery stores per 100,000 residents than the racially heterogeneous, middle-SEP
      community. Mean overall selection and price of fresh produce at stores did not
      differ among communities. CONCLUSIONS: Increasing access to high-quality fresh
      produce in low-income communities of color is a critical first step toward
      improving health through better dietary practices in this population.

PMID- 16599385
TI  - Cross-cultural validation of the hill-bone compliance to high blood pressure
      therapy scale in a South African, primary healthcare setting.
AB  - OBJECTIVES: Hypertension is prevalent, under-diagnosed, and inadequately treated
      in Black South Africans. However, few studies have addressed barriers to
      hypertension care and control in this community. The aim of this study was to
      validate the Hill-Bone Compliance to High Blood Pressure Therapy Scale (HB Comp
      Scale) for use in a South African primary healthcare setting. This instrument
      consists of three subscales, medications-compliance, appointment making, and salt
      intake. METHODS: A demographic questionnaire and the HB scale were translated
      into the first language of the subjects and then back-translated into English.
      Hypertensive patients (N=98) were recruited from primary healthcare clinics in
      Cape Town. Blood pressure was measured with an Omron electronic blood pressure
      manometer, after 5 min of seated rest. Item-analysis was conducted to determine
      internal consistency of the HB Comp Scale; Spearman rank order correlations were
      used to assess the relationship between compliance scores and blood pressure.
      RESULTS: A modified scale consisting of only 10 items demonstrated reasonable
      internal consistency (item-total correlations all >.31, and a standardized
      Cronbach alpha of 0.79), with an average interitem correlation of .26. In
      addition, the modified scale had significant predictive validity in that
      noncompliance predicted higher diastolic blood pressures (p=.21, P<.05) and
      medication noncompliance tended to predict higher systolic blood pressures
      (p=.20, P<.06). Appointment-making and dietary salt-intake subscales were not
      internally consistent. CONCLUSIONS: We demonstrated criterion validity and
      internal consistency for a modified Hill-Bone Compliance Scale, in Black, urban,
      hypertensive, South African patients. Results compare favorably with those from
      an urban African-American setting (standardized Cronbach alpha was .74-.84).

PMID- 16599386
TI  - Blood pressure survey in two communities in the Volta region, Ghana, West Africa.
AB  - BACKGROUND: The prevalence of hypertension appears to be increasing in the
      developing world. A study published in 2003 showed a crude prevalence of 28.3% in
      the capital city of Accra, Ghana. The prevalence of hypertension in many rural
      areas of the developing world is not known. OBJECTIVES: 1) To survey two rural
      populations for hypertension; 2) to identify factors that may be associated with
      hypertension; 3) to assess the level of control of hypertension. STUDY
      DESIGN/SETTING/PARTICIPANTS: 287 volunteers surveyed during market day in two
      villages in the Volta region of Ghana. Blood pressures were obtained after
      obtaining demographic and historical information. All individuals age > or = 17
      were included in the analysis. Hypertension was defined as a blood pressure > or
      = 140/90 mm Hg on two separate occasions. RESULTS: The prevalence of hypertension
      in the populations surveyed was 32.8%. Factors associated with hypertension that
      reached statistical significance (P<.05) included family history of hypertension,
      consumption of akpeteshie, location of blood pressure assessment, and consumption
      of non-smoked fish (inverse association). More than 80% of those with a history
      of hypertension had an elevated blood pressure at the time of screening.
      CONCLUSIONS: The proportion of hypertension in the rural populations surveyed is
      higher when compared to true prevalence studies and is most likely due, in part,
      to selection biases. The low hypertension control rates identified in people with
      a history of hypertension would need to be considered when determining whether to
      expand hypertension screening programs or to improve access to treatment for
      those with known hypertension in these resource-limited areas.

PMID- 16599387
TI  - A review of psychosocial stress and chronic disease for 4th world indigenous
      peoples and African Americans.
AB  - Public health literature indicates that psychosocial stress is an important
      contributor to chronic disease development. However, there is scant research on
      the health effects of stress for minority groups, who suffer from a high burden
      of chronic disease. This paper provides a review of studies that examine the
      relationship between psychosocial stress and chronic disease for 4th world
      indigenous groups and African Americans. A total of 50 associational and 15
      intervention studies fit the inclusion criteria for this review. A range of
      chronic diseases, as well as harmful health behaviors, were associated with
      psychosocial stress for indigenous peoples and African Americans, with much
      stronger findings for mental rather than physical health outcomes. Several stress
      moderating factors were also identified and a small body of intervention research
      suggests that transcendental meditation and group-oriented stress management may
      be effective in reducing psychosocial stress and its effects for African
      Americans and 4th world indigenous groups respectively.

PMID- 16599388
TI  - For the patient. Helping black mothers to help their daughters exercise.

PMID- 16599389
TI  - For the patient. Does income level affect low birth weight?

PMID- 16599390
TI  - For the patient. How anxiety affects health and quality of life for the growing
      elderly population.

PMID- 16599391
TI  - For the patient. Stressful life events add to poor quality of life for young
      Black men with high blood pressure.

PMID- 16599392
TI  - For the patient. Barriers and solutions to motivating men to undergo prostate
      cancer screening.

PMID- 16599393
TI  - For the patient. Tobacco addiction differs between African-American and White
      teenagers.

PMID- 16599394
TI  - For the patient. Factors that could improve control of high blood pressure among
      Korean Americans.

PMID- 16599395
TI  - For the patient. Understanding best approaches for smoking cessation programs for
      American Indians.

PMID- 16599396
TI  - For the patient. Differences in behaviors that place US-born vs foreign-born
      individuals at greater risk of heart disease.

PMID- 16599397
TI  - Probable cigarette dependence, PTSD, and depression after an urban disaster:
      results from a population survey of New York City residents 4 months after
      September 11, 2001.
AB  - Disaster exposure may exacerbate psychopathology and substance-related disorders.
      Four months after September 11, 2001, using random-digit dialing to contact a
      representative sample of adults (N = 2001) living in New York City, we assessed
      cigarette smoking and symptoms of probable cigarette dependence using measures
      from the National Survey on Drug Use and Health. A total of 36.8% of smokers
      reported increased cigarette use; 10.4% of respondents reported three or more
      symptoms of cigarette dependence and were considered cases of probable cigarette
      dependence based on DSM-IV criteria. Cases were more likely to report an increase
      in cigarette use since September 11 than non-cases (69.4% among cases vs. 2.2%
      among non-cases, p < 0.001). Cases were more likely to have probable
      posttraumatic stress disorder (PTSD) and depression than non-cases (18.1% vs.
      5.7% for PTSD, p < 0.001; 23.6% vs. 6.0% for depression, p < 0.001). Increased
      cigarette use since September 11 was associated with probable PTSD among cases
      (23.4% vs. 6.4%, p = 0.011) and non-cases (15.1% vs. 5.5%, p = 0.034) but was
      associated with probable depression only among cases of probable cigarette
      dependence (28.3% vs. 13.3%, p = 0.027). This study showed the co-occurrence of
      probable cigarette dependence with increased cigarette use and the co-occurrence
      of probable cigarette dependence with probable PTSD and depression after
      September 11.

PMID- 16599398
TI  - Stress, smoking, and 9/11/01.

PMID- 16599399
TI  - Clinical tasks of the dynamic interview.
AB  - We examined psychodynamic interview tasks and techniques to identify clinical
      actions that improve or impede exploration of subjects' emotional responses,
      conflicts, defenses, and central relationship themes. This article extends
      previous quantitative studies (Perry, Fowler, & Greif, unpublished; Perry,
      Fowler, & Semeniuk, 2005) by examining interview vignettes in 50-minute
      psychodynamic research interviews. We conducted qualitative analyses on 72
      dynamic research interviews given by 26 subjects to delineate categories of tasks
      and interventions. Results indicated five broad tasks of the dynamic interview:
      1) Frame Setting; 2) Offering Support; 3) Exploring Affect; 4) Offering Trial
      Interpretations; and 5) Providing a Formulation and Feedback of relationship
      themes and conflicts. We further selected two interviews each from 10 subjects,
      in which there was a difference of one standard deviation or greater on the
      Overall Dynamic Interview Adequacy scale (Perry, 1999), and interviewer errors
      from the Therapeutic Alliance Analogue scale (Perry, Brysk, & Cooper, 1989). We
      utilized excerpts from these interviews to highlight the importance of these
      tasks and techniques in deepening discussion of dynamically meaningful material.

PMID- 16599400
TI  - Patterns of response and non-response in interpersonal psychotherapy: a
      qualitative study.
AB  - This qualitative analysis of response and non-response in interpersonal
      psychotherapy (IPT) was conducted on sessions that had been audiotaped for a
      randomized clinical trial designed to identify patient predictors of treatment
      response to psychotherapy for depression. A thematic analysis was conducted on
      ten sets of IPT sessions (120 hours) to explore the process of change. Analysis
      of these sessions revealed a pattern associated with improvement in mood. This
      pattern involved struggling with the symptoms; deconstructing interpersonal
      patterns; altering the pattern; and reconstructing a sense of self. Because the
      analysis revealed that not all participants' transcripts showed an engagement
      with this pattern, a further analysis revealed characteristics associated with
      response and non-response. These characteristics were: an ability to engage in
      multiple perspectives, an awareness of others' feelings, a desire to make change,
      a sense of self-responsibility, an ability to use a range of communication
      strategies, a desire to act cooperatively, and an ability to engage with the
      therapist.

PMID- 16599401
TI  - A pathway to spirituality.
AB  - The phenomenology of mystical experiences has been described throughout all the
      ages and in all religions. All mystical traditions identify some sense of union
      with the absolute as the ultimate spiritual goal. I assume that the pathway to
      both theistic and secular spirituality and our readiness to seek a solution in a
      psychological merger with something beyond the self evolves out of our human
      experience. Spirituality is one of man's strategies for dealing with the
      limitations of the life cycle, separation and loss, biological fragility,
      transience, and non-existence. Spirituality may serve as the affective component
      to a belief system or myth that is not rooted in scientific evidence but is lived
      as if it is true. Spirituality may take many forms, but I will suggest that in
      some instances it may serve as a reparative process in which one creates in the
      external world, through symbolic form, a nuance or facet of an internalized
      mental representation which has become lost or is no longer available to the
      self; or it may represent the continuity of the self-representation after death
      through a self-object merger. Lastly I will illustrate from the writings of two
      of our greatest poets, Dante Alighieri and William Wordsworth, how their poetry
      became interwoven with a profound spirituality. In Dante we will see the
      elaboration of a religious spirituality, while in the writings of Wordsworth a
      secular spirituality emerges interwoven with nature and belatedly his
      identification with "tragic man" as his mythos.

PMID- 16599402
TI  - Effects of adolescent trauma exposure on risky behavior in college women.
AB  - Individuals with sexual assault or abuse histories are likely to engage in risky
      sexual and other self-destructive behaviors. Studies of these behaviors, however,
      have focused on target traumatic events without accounting for other events in
      the participant's history, recency of the events, and/or developmental level at
      time of occurrence. The present study addressed some of these confounds by
      creating groups with unique and non-overlapping trauma histories among adolescent
      participants whose first trauma occurred at age 12 or older. Sophomore women from
      six regional campuses were screened in a two-stage procedure, and 209 of 363
      final interviewees were included in the present report. These were assigned to a
      no trauma group, or to one of five groups with a unique trauma history: a single
      traumatic loss, a single physical assault, a single sexual assault, ongoing
      sexual or physical abuse, or multiple single traumas. Risky sexual behavior,
      suicidal ideation, and elevated perpetration of violence were most prominent
      among those with ongoing abuse exposure, although a single exposure to
      interpersonal violence during adolescence was sufficient for some risky
      behaviors. Major depression (MDD) and posttraumatic stress disorder (PTSD) were
      associated with many of the behaviors, and may serve to heighten risk.

PMID- 16599403
TI  - Determination of diphacinone residues in Hawaiian invertebrates.
AB  - A reversed-phase ion-pair liquid chromatographic analysis combined with a solid
      phase extraction clean-up method is used to assess the quantity of diphacinone
      residue found in invertebrates. Three invertebrate species are exposed to
      commercially available diphacinone-fortified bait used for rat control. The
      invertebrate samples are collected, frozen, and shipped to the laboratory. The
      samples are homogenized after cryogenic freezing. A portion of the homogenized
      samples are extracted with acidified chloroform-acetone, followed by cleanup with
      a silica solid-phase extraction column. Diphacinone is detected by UV absorption
      at 325 nm after separation by the chromatographic system. The method limit of
      detection (MLOD) for snail and slug samples averaged 0.055 and 0.066 mg/kg,
      respectively. Diphacinone residues in snail tissue ranges from 0.83 to 2.5 mg/kg
      for Oxychilus spp. The mean recoveries from snails at 0.20 and 2.0 are 97 +/- 21%
      and 84 +/- 6%. Diphacinone residues in slug tissue ranges from 1.3 to 4.0 mg/kg
      for Deroceras laeve and < MLOD to 1.8 mg/kg for Limax maximus, respectively. The
      mean recoveries from slugs at 0.20 and 2.0 mg/kg are 91% +/- 15% and 86% +/- 5%.

PMID- 16599404
TI  - Systematic parameter screening for capillary electrophoresis monitoring of
      surfactants on silicon wafer surfaces by designed experiments.
AB  - The surface purity of silicon wafers is an important parameter to monitor for
      yield improvement of semiconductor devices in a production line. Surfactants are
      used to reduce the surface potential in order to facilitate the removal or
      cleaning of particles and metals. Traces of surfactant residues from the cleaning
      bath may still be present on the wafer surface after the final cleaning step. In
      this report, two capillary electrophoresis (CE) methods for the analysis of
      dodecylbenzene sulfonate (DBS) are developed for monitoring the surfactant
      residues in the wafer manufacturing process. One method is developed for the
      sensitive determination of all DBS homologues and isomers in one single peak.
      Another method is developed for the fingerprint analysis of the homologues and
      isomers of DBS. The Taguchi methodology was used as a systematic optimization
      tool for the DBS analysis by CE. The experiments were evaluated by calculating
      the signal-to-noise ratio values with four responses. The lowest detection limit
      for DBS was 15 microg/L at 95% confidence level. The percent recovery of
      surfactant was between 90% and 110%.

PMID- 16599405
TI  - Simple high-performance liquid chromatographic method for the determination of
      tetramethylpyrazine phosphate in very small volumes of dog plasma: application to
      a pharmacokinetic study.
AB  - A rapid and sensitive high-performance liquid chromatographic (HPLC) method is
      developed for the determination of tetramethylpyrazine phosphate, an antiplatelet
      aggregation agent, in 100 microL of dog plasma. Sample preparations are carried
      out by deproteinization with an internal standard (carbamazepine) solution in
      acetonitrile. An aliquot of the supernatant (20 microL) is directly injected into
      an HPLC apparatus with methanol-phosphate buffer (0.01M, pH 3.0) (62:38, v/v) as
      the mobile phase at a flow rate of 1.0 mL/min. Separation is performed with a C18
      column at 30 degrees C. The peak is detected using a UV detector set at 279 nm.
      The capacity factors are 1.48 for tetramethylpyrazine phosphate and 2.09 for
      carbamazepine, with a total run time of 10 min. The calibration curve is linear
      in the 0.2-50-microg/mL range. The limit of detection is 0.05 microg/mL. Mean
      recoveries are 92.6-98.1%. The within- and between-day variation coefficients are
      less than 4.9% and 7.5%, respectively. The present method has been successfully
      used to provide pharmacokinetic data after oral administration of
      tetramethylpyrazine phosphate pulsincap capsules and immediate-release tablets to
      dogs.

PMID- 16599406
TI  - Use of SPME-GC-MS in the study of time evolution of the constituents of saffron
      aroma: modifications of the composition during storage.
AB  - The effect of storage on the composition of saffron aroma is studied. Six samples
      of saffron from different areas of Italy are analyzed by solid-phase
      microextraction-gas chromatography-mass spectrometry. Samples 1, 2, and 3 are
      derived from cultivations of Crocus sativus in the zone of Salerno (Southern
      Italy) from 2000 to 2002. Samples 4, 5, and 6 are derived from cultivations in
      Sardinia, Italy (from 1998, 2000, and 2001, respectively). In all samples, 3,5,5
      trimethyl-2-cyclohexen-1-one; 3,5,5-trimethyl-2-cyclohexen-1,4-dione; safranal;
      and 2,4,4-3,5,5-trimethyl-2-cyclohexen-1,4-dione; safranal; and 2,4,4-trimethyl-6
      hydroxy-3-carboxaldehyde-2,5-cyclohexadien-1-one are found. 5,5-Dimethyl-2
      methylene-1-carboxaldehyde-3-cyclohexene; 3,5,5-trimethyl-1,4-cyclohexandione;
      and beta-ionone are found with nonanal, dihydro-beta-ionone, and 2,6-di-t
      butylphenol. Safranal is the main component in all of the samples. The most
      important changes are in the presence of alcohols and aldehydes and oxidation
      products of the major terpenoids components. Furthermore, the presence of
      safranal--the most important constituent of the flavor--changes during the time,
      increasing during 3 years, then decreasing after 5 years.

PMID- 16599408
TI  - Liquid chromatographic enantiomer separation of racemic amine using chiral crown
      ether stationary phase.
AB  - Direct enantioseparation of racemic amine, amino-thiophene-2-yl-acetonitrile
      (TAN), on chiral crown ether stationary phase [Crownpak CR (+)] is described in
      this study. The elution behavior and the effect of acid additives on resolution
      of racemic amine, TAN, is intensely investigated. Moreover, the chiral
      recognition mechanism in this specific system is proposed based on computational
      methods with the density functional theory. Diastereomeric complexation of the
      ammonium ion of racemic amine inside the cavity of chiral crown ether appears
      essential for the chiral discrimination. The pH of the mobile phase containing
      acid additives also acts as an important factor for the chiral recognition.

PMID- 16599407
TI  - Extraction and monitoring of phytoecdysteroids through HPLC.
AB  - The size of the phytoecdysteroids family is rapidly growing. Recent data shows
      over 250 ecdysteroid analogs have been identified so far in plants. It is
      theorized that there are over 1000 possible structures, which might occur in
      nature, but it is a fact that ecdysteroids usually occur in plants as a complex
      cocktail of structurally different compounds. Among these compounds, the major
      component is usually the common ecdysteroid-like 20-hydroxyecdysone. Ecdysteroids
      are polar steroids, almost sugar-like in their solubility properties. Extraction
      and purification of ecdysteroids (polyhydroxy steroids) is complicated by their
      polar nature and poor crystallizing properties. These properties make them
      difficult to separate from other polar plant constituents. Besides, this plant
      extract is very often processed by multistep procedures to isolate the major and
      minor ecdysteroids from the new or existing sources. A simplified scheme
      consisting of a few extraction steps for the purification of ecdysteroid from
      plants is in great demand. A quantitative approach through high-performance
      liquid chromatography has been initiated for developing an easy method for the
      extraction of ecdysteroids from Ipomoea hederacea (kaladana) seeds.

PMID- 16599409
TI  - Rapid and sensitive method for the determination of propylene oxide in cigarette
      mainstream smoke by gas chromatography-mass spectrometry.
AB  - A rapid method using gas chromatography-mass spectrometry for the analysis of
      propylene oxide in cigarette mainstream smoke is reported. Validation data show
      the method, which requires a minimum of sample preparation, to be selective,
      sensitive, reliable, and robust. Propylene oxide is found in the University of
      Kentucky Reference Cigarettes 1R4F and 2R4F at concentrations of 0.93 and 0.65
      microg/cigarette, respectively, with a quantitation limit of 0.135
      microg/cigarette.

PMID- 16599411
TI  - High-performance liquid chromatographic assay of indomethacin in porcine plasma
      with applicability to human levels.
AB  - A high-performance liquid chromatography (HPLC) assay is described for the
      determination of indomethacin in porcine plasma using acetonitrile to precipitate
      plasma proteins and for the one-step extraction. Calibration curves (using the
      internal standard method) are linear (r2 > 0.98) over the concentration range of
      50.0 to 3000 ng/mL in both mobile phase and plasma. Precision, expressed as the
      inter- and intraday coefficient of variation (n = 5), is < 7% on the same day and
      < 5% between days at each plasma control sample of 300, 1000, and 3000 ng/mL,
      respectively. System precision, calculated as the coefficient of variation (n =
      5), is < 7% at 3000 ng/mL of indomethacin, and the limit of quantitation in
      plasma is 50 ng/mL. The absolute recovery for both indomethacin and the internal
      standard (mefenamic acid) from plasma is over 97% (n = 3), and the concentrations
      do not deviate more than -2.9% to 2.4% from their actual values. The specificity
      of the method is confirmed. This technique is thus reported to be both rapid and
      specific. The real advantage is the small sample volume required (500 microL),
      which allows it to be considered for the quantitation of indomethacin in plasma
      from paediatric patients.

PMID- 16599410
TI  - Optimization and validation of HPLC-UV-DAD and HPLC-APCI-MS methodologies for the
      determination of selected PAHs in water samples.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants resulting
      from emissions of a variety of sources including industrial combustion, discharge
      of fossil fuels, and residential heating. Because of their mutagenic and
      carcinogenic properties, the study of PAHs in environmental matrices is of great
      importance. In this work, the extraction of 9 out of the 16 PAH priority
      pollutants according to the U.S. Environmental Protection Agency is carried out
      through liquid-liquid extraction (LLE) and solid-phase extraction (SPE). The
      determination of PAHs is made by high-performance liquid chromatography with
      diode-array detection and liquid chromatography-atmospheric pressure chemical
      ionization mass spectrometry. Between the extraction techniques used, LLE is
      revealed to be efficient in the extraction of the higher molecular weight PAHs,
      though SPE is adequate for the extraction of all PAHs. In the real water samples
      analyzed, no PAH is detected under the analysis conditions used.

PMID- 16599412
TI  - Drug monitoring and toxicology: a procedure for the monitoring of oxcarbazepine
      metabolite by HPLC-UV.
AB  - This article describes a rapid high-performance liquid chromatographic (HPLC)
      method for the measurement of the primary metabolite of oxcarbazepine. Following
      a simple precipitation step, 10,11,-dihydro-10-hydroxy-5H-dibenzo(b,f)azepine-5
      carboxamide is quantitated (5-60 microg/mL) by analysis on an HPLC-UV system. The
      instrument time is less than 5 min per injection, an improvement over most
      published methods. The assay's limit of quantitation, linearity, imprecision, and
      accuracy adequately cover the therapeutic range for appropriate patient
      monitoring. In comparison to other published methods, this procedure would be of
      interest to clinical laboratories because it employs a precipitation step for
      sample preparation, instead of conventional yet time-consuming solid-phase
      extraction.

PMID- 16599413
TI  - The behavior of some phenothiazines and their demethylated derivatives in
      reversed-phase liquid chromatography.
AB  - Three selected phenothiazines and their demethylated derivatives are
      chromatographed on different C18 bonded reversed-phase liquid chromatography
      columns. A quadratic equation fits the relationship log k versus the organic
      modifier percentage. When acetonitrile is the organic modifier, the demethylated
      derivative is eluted before the parent compound, whereas it is eluted after when
      methanol is the organic modifier. The log kw values are therefore different.
      Selectivity between the metabolite and the parent compound is higher with
      methanol.

PMID- 16599414
TI  - Gas chromatography problem solving and troubleshooting. Isotopically-labeled
      internal standards.

PMID- 16599415
TI  - Diagnosis and management of juxtafacet cysts.
AB  - Juxtafacet cysts are lesions that are associated with spinal facet joints.
      Although these lesions are frequently noted as incidental findings on imaging
      studies of the spine, they may produce symptoms in some patients. Juxtafacet
      cysts can mimic herniated discs, resulting in symptoms from focal nerve root
      and/or spinal cord compression. Some of these lesions are associated with spinal
      instability, and patients may require spinal fusion to address this underlying
      disorder. Conservative therapy for symptomatic lesions is often unsuccessful,
      although there are reports of spontaneous resolution of these cysts as well as
      the symptoms associated with them. Surgical therapy should be focused on
      decompression of the lesions causing nerve root compression and the accompanying
      symptoms, while recognizing that instability requiring fusion may be present in
      some but not all cases.

PMID- 16599416
TI  - Minimally invasive transforaminal lumbar interbody fusion with unilateral pedicle
      screw fixation.
AB  - OBJECT: Posterior lumbar interbody fusion (PLIF) has been shown to be effective
      in the treatment of axial low-back pain. Minimally invasive spine surgery for
      arthrodesis has several advantages, including quicker patient recovery, less
      postoperative pain, and less destruction of adjacent tissue. The purpose of this
      paper is to evaluate the clinical outcomes after PLIF procedures in which
      unilateral pedicle screw fixation was used. METHODS: Prospective data were
      collected in 34 patients undergoing a one-level minimally invasive transforaminal
      lumbar interbody fusion (TLIF) in 2003. Conservative therapy, including physical
      therapy and aggressive multimodality pain management, had failed in all patients.
      Selection was based on magnetic resonance imaging studies demonstrating
      degenerative disc disease. All patients underwent a unilateral TLIF procedure in
      conjunction with posterior unilateral pedicle screw fixation. Twenty patients in
      whom the follow-up duration was longer than 6 months were included in this study.
      The follow-up duration in all patients ranged from 6 to 12 months. Seventeen
      (85%) of 20 patients had a good result, which was defined as a greater than 20
      point reduction in the Oswestry Disability Index (ODI) score. The other three
      patients had no improvement. The mean preoperative ODI score of 57 improved to 25
      after surgery (p < 0.005). In the 17 patients who demonstrated improvement, the
      mean ODI score improved from 57 to 18. The patients' visual analog scale pain
      scores improved from 8.3 to 1.4 (p < 0.005) after surgery. In patients who
      received Workers' Compensation, three (75%) of four improved. Follow-up
      computerized tomography scans were obtained in all 20 patients at 6 months. At
      that time, 13 of the patients demonstrated some degree of fusion, and no
      symptomatic pseudarthrosis was noted. CONCLUSIONS: Minimally invasive TLIF in
      conjunction with unilateral pedicle screw instrumentation is an effective
      treatment for axial low-back pain in appropriately selected patients.

PMID- 16599417
TI  - Simple closure following transsphenoidal surgery. Technical note.
AB  - The most common nonendocrine complication after transsphenoidal surgery is
      cerebrospinal fluid (CSF) leak. Many neurosurgeons have advocated the routine
      reconstruction of the floor of the sella turcica using autologous fat, muscle,
      fascia, and either cartilage or bone after transsphenoidal surgery to prevent
      postoperative CSF fistulas. However, the use of autologous grafting requires a
      second incision, prolongs operative time, and adds to the patient's postoperative
      discomfort. In addition, the presence of sellar packing may interfere with the
      interpretation of postoperative images. To avoid these disadvantages, the authors
      suggest that routine sellar reconstruction or closure after transsphenoidal
      surgery is unnecessary unless an intraoperative CSF leak is encountered. The
      incidence of postoperative CSF leakage in the patients reported on in this series
      is no higher than that reported by others, and no other complications such as
      pneumatocele have been encountered in approximately 2700 patients in whom no
      intraoperative CSF leak was encountered. The authors conclude that routine
      closure of the floor of the sella turcica or sphenoid is unnecessary in the
      absence of intraoperative CSF leak.

PMID- 16599418
TI  - Treatment of lumbar synovial cysts using minimally invasive surgical techniques.
AB  - OBJECT: Lumbar synovial cysts are a potential cause of radiculopathy and back
      pain, and the definitive treatment is the complete excision of the cyst. This
      report summarizes the authors' preliminary clinical experience with the minimally
      invasive resection of lumbar synovial cysts. METHODS: Nineteen patients (nine men
      and 10 women) with symptomatic synovial cysts underwent minimally invasive
      resection. The mean patient age was 64 years of age (range 43-80 years). The
      presenting symptom was radiculopathy in 16 patients, low-back pain in two, and
      lower-extremity weakness in one. There were 16 cases of a cyst located at the L4
      5 level, two at L3-4, and one at L5-S1. The mean cyst diameter was 13.7 mm (range
      3-30 mm). The mean follow-up time was 16 months (range 4-29 months). Clinical
      outcomes were graded, based on the Macnab modified criteria, as excellent, good,
      fair, or poor. Eighteen patients (95% of cases) reported either excellent (10
      patients) or good (eight patients) results, and a fair result was reported by one
      patient (5% of cases). The mean operative time was 158 minutes (range 75-270
      minutes), and the average intraoperative blood loss was 31 ml (range 10-100 ml).
      Two patients had intraoperative dural tears that resulted in cerebrospinal fluid
      leaks that resolved following primary closure. CONCLUSIONS: Synovial cysts can be
      safely and effectively treated using minimally invasive surgical techniques. Long
      term follow up is required to determine whether this approach results in less
      need for fusion than conventional surgical approaches.

PMID- 16599419
TI  - Placement of percutaneous pedicle screws without imaging guidance.
AB  - Pedicle screw (PS) instrumentation provides an exceptionally rigid construct to
      promote fusion in cases of spinal trauma and degenerative disease. Although the
      safety of traditional open techniques for PS placement has been well documented,
      there are no large series in the literature in which the safety of percutaneously
      placed PSs has been examined. Because the advantages of minimally invasive spine
      surgery are becoming more widely recognized, especially in regard to the
      lessening of morbidity caused by pain and blood loss, there will be a greater
      demand for spine surgeons to place PSs percutaneously. During a 2-year period,
      the authors placed 287 PSs percutaneously with the aid of intraoperative
      fluoroscopy. Only one of these screws was later found to have breached the spinal
      canal, yielding a breach rate of 0.35% for percutaneously placed PSs (one of
      287).

PMID- 16599420
TI  - Unilateral pedicle screw instrumentation for minimally invasive transforaminal
      lumbar interbody fusion.
AB  - OBJECT: Clinical and radiographic results were assessed to determine the clinical
      outcomes and fusion rate in eight consecutive patients selected for minimally
      invasive transforaminal lumbar interbody fusion (TLIF) in which a percutaneous
      pedicle screw system was used unilaterally. METHODS: Eight patients underwent one
      level, minimally invasive TLIF in which a percutaneous pedicle screw system was
      used only on the side where facets were removed for interbody access. Clinical,
      economic, functional, and radiographic data were recorded preoperatively and at 6
      months postoperatively. The mean 6-month change in the modified Prolo Scale score
      was 7, and osseous interbody bridging assessed on coronal and sagittal
      computerized tomography studies was seen in all patients. CONCLUSIONS: The use of
      unilateral percutaneous pedicle screw instrumentation for the minimally invasive
      TLIF procedure provides excellent clinical results and is an option in selected
      patients.

PMID- 16599422
TI  - Minimally invasive transforaminal lumbar interbody fusion: indications,
      technique, and complications.
AB  - The authors provide an overview of the minimally invasive transforaminal lumbar
      interbody fusion (TLIF) procedure including indications, technique, and
      complications. This novel technique is a method of achieving circumferential
      lumbar fusion using a unilateral dorsal approach. Minimally invasive TLIF uses a
      tubular retractor that is inserted via a muscle-dilating exposure, thereby
      minimizing the approach-related morbidity. This procedure is ideal for refractory
      mechanical low-back and radicular pain associated with spondylolisthesis,
      degenerative disc disease, and recurrent disc herniation. The authors' clinical
      experience and review of the medical literature indicate that TLIF can be
      effectively and safely performed in a minimally invasive fashion.

PMID- 16599421
TI  - Paramedian approach for transforaminal lumbar interbody fusion with unilateral
      pedicle screw fixation. Technical note and preliminary report on 47 cases.
AB  - Lumbar fusion is a commonly performed procedure for a variety of pathological
      conditions, and it is frequently used in the treatment of degenerative lumbar
      instability that is refractory to medical management. Pedicle screws and
      interbody devices have been used for internal fixation to promote arthrodesis,
      prevent nonunion, and facilitate early mobilization. Recently, attempts have been
      made to reduce the morbidity associated with lumbar fusion by using a variety of
      minimally invasive techniques. Many minimally invasive lumbar fusion procedures
      require specialized retractors, implants, image guidance systems, or insertion
      instruments. Other minimally invasive techniques are primarily applied to an
      ideal patient population (thin, healthy, and with no previous surgery). The
      authors describe their experience with a paramedian approach for minimally
      invasive transforaminal lumbar interbody fusion (TLIF) with unilateral pedicle
      screw (PS) fixation. This procedure requires only standard implants, instruments,
      and retractors, with direct visualization for all aspects of the procedure. The
      authors describe encouraging early results in a challenging patient population in
      which there was a high incidence of obesity, medical comorbidities, and previous
      surgery at the same level. The paramedian approach for TLIF performed using
      unilateral lumbar PSs has yielded successful outcomes in this series of 47
      patients, and further study of this technique may help define its role as a
      minimally invasive procedure for spinal fusion.

PMID- 16599423
TI  - Anterior transvertebral interbody cage with posterior transdiscal pedicle screw
      instrumentation for high-grade spondylolisthesis. Technical note.
AB  - Adult high-grade degenerative spondylolisthesis represents the extreme end of the
      spectrum for spondylolisthesis and is consequently rarely encountered. Surgical
      management of high-grade spondylolisthesis requires constructs capable of
      resisting the shear forces at the slipped L5-S1 interspace. The severity of the
      slip, sacral inclination, and slip angle may make conventional approaches to 360
      degrees fusion difficult or hazardous. Transdiscal pedicle screw fixation,
      transvertebral fibular graft fusion, and transvertebral cage fixation are
      techniques that have been developed to establish anterior column load sharing and
      to resist shear forces at the L5-S1 interspace, given the anatomical constraints
      accompanying high-grade spondylolisthesis. In this technical note the authors
      describe the procedure for implanting an in situ anterior L5-S1 transvertebral
      cage and performing L4-5 anterior lumbar interbody fusion, followed by placement
      of posterior S1-L5 vertebral body transdiscal pedicle screws for management of
      high-grade spondylolisthesis.

PMID- 16599424
TI  - Clinical and radiographically/neuroimaging documented outcome in transforaminal
      lumbar interbody fusion.
AB  - OBJECT: Although transforaminal lumbar interbody fusion (TLIF) is an increasingly
      popular surgical technique, there are a limited number of studies in which
      investigators have stratified outcome data with respect to surgical indications
      or documented radiographically proven and clinical results with respect to disc
      space height (DSH). The authors conducted a study to evaluate the long-term
      outcomes after TLIF with respect to surgical indication and
      radiographic/neuroimaging results. METHODS: Thirty-three consecutive TLIF-treated
      patients underwent follow-up investigation for a mean of 37 months. Isthmic
      spondylolysis was present in eight patients, recurrent disc herniation in 14, and
      degenerative disc disease (DDD) in 11. The operative technique involved the
      placement of interbody structural allograft, pedicle screw instrumentation, and
      morcellized autograft in the anterior interbody space and the contralateral
      intertransverse gutter. Surgery was performed at L4-5 in 16 patients, L5-S1 in
      14, L3-4 in two, and both L4-5 and L5-S1 in one patient. Preoperative symptoms
      were back pain (in 91% of cases), leg pain (in 94%), sensory loss (in 67%), and
      motor deficits (in 30%). Postoperatively, back pain was improved in 67% of the
      patients, unchanged in 27%, and worsened in 7%. Leg pain improved in 80% of
      patients, was unchanged in 10%, and worsened in 10%. Outcome, as measured using
      the Prolo Functional and Economic Scales, improved from a score of 4.9 to 7. In
      patients with spondylolysis and recurrent disc herniation outcomes were better
      than in those with DDD only. There was no correlation of outcome with symptom
      duration, patient age, or level of surgery. In an independent review of pre- and
      late postoperative radiographs no significant differences in lordosis angles,
      Cobb angles, or DSHs were found. Fusion occurred in all cases. CONCLUSIONS: The
      TLIF procedure was associated with good clinical outcomes and a high fusion rate
      but no change in the DSH. Patients who present with spondylolysis and recurrent
      herniations experience better outcome than those with degenerative disease alone.

PMID- 16599426
TI  - Freezing halide ion solutions and the release of interhalogens to the atmosphere.
AB  - The effect of freezing on a variety of acidified and neutral, nitrite ion and
      halide-containing mixtures has been investigated using UV/vis spectroscopy.
      Several trihalide ions were formed and monitored, including I(2)Cl(-), I(2)Br(-),
      ICl(2)(-) and IBr(2)(-). A mechanism to explain the observations is given in
      terms of steps involving INO and the nitroacidium ion, [H(2)ONO](+). The
      transformation of sea salt components to specific trihalide ions by freezing
      represents a potentially important process in a polar atmospheric context. This
      is because the dichloro- and dibromo-trihalide ions can release chlorine- and
      bromine-containing gases, which are key intermediates in ozone destruction.

PMID- 16599425
TI  - Intraventricular meningiomas: a clinicopathological study and review.
AB  - OBJECT: Intraventricular meningiomas are rare tumors. The origin of these tumors
      can be traced to embryological invagination of arachnoid cells into the choroid
      plexus. The authors analyzed data that they had collected to study the
      clinicopathological aspects and review the origin, presentation, imaging, and
      management of these tumors. METHODS: In this retrospective analysis, the authors
      describe the cases of 12 patients who had received a diagnosis of
      intraventricular meningioma and underwent surgery for the tumors. Nine of these
      patients were men and three were women. Features of neurofibromatosis Type 2 were
      present in two of the women. Nine of the tumors were located in the lateral
      ventricles, one was in the third ventricle, and two were in the fourth ventricle.
      Raised intracranial pressure (ICP) was the universal presentation in all the
      patients, and the preoperative diagnoses were confirmed on neuroimaging studies.
      Excision was performed using the parietooccipital (trigonal) approach for lateral
      ventricle tumors, the transcortical-transventricular route for the third
      ventricle tumor, and suboccipital craniectomy for fourth ventricle tumors.
      Postoperatively, one patient died and the others experienced resolution of their
      symptoms. Histopathological features of these tumors were similar to those seen
      in meningiomas in other locations. CONCLUSIONS: Intraventricular meningiomas are
      slow-growing tumors that become large prior to detection. Although they are
      commonly seen in the lateral ventricles, they occur in the third and fourth
      ventricles as well. Presentation is in the form of raised ICP with no localizing
      features; therefore the diagnosis is based on imaging studies. Hydrocephalus
      occurs due to obstruction of cerebrospinal fluid pathways. Excision requires
      planning to avoid eloquent cortex incision. The histopathological features are
      varied, although most of the tumors in the study were angiomatous meningiomas.
      These tumors are no different histologically from tumors that are dural in
      origin. No recurrence has been reported.

PMID- 16599427
TI  - An anomalous bond angle in 116H2. Theoretical evidence for supervalent
      hybridization.
AB  - The electronic structure and geometry of the superheavy group VI molecule
      (116)H(2) are examined and compared to those of the lighter group analogues H(2)O
      PoH(2). The spin-orbit interaction is found to lengthen the (116)-H bond and more
      importantly lead to a modest but significant H-(116)-H bond angle increase. It is
      suggested that the latter is the result of a rehybridization of the valence 7p
      orbitals with a "supervalent" 8s orbital of element 116.

PMID- 16599428
TI  - Longitudinal electron spin relaxation induced by degenerate electron exchange as
      studied by time-resolved magnetic field effects.
AB  - T(1) paramagnetic relaxation of radical ions induced by degenerate electron
      exchange (DEE) reactions is studied theoretically and experimentally. Our
      theoretical analysis shows that T(1) relaxation time is well described by the
      Redfield theory at arbitrary values of the characteristic DEE time tau.
      Longitudinal relaxation of norbornane (NB) radical cation is studied by means of
      the time-resolved magnetic field effects (TR-MFE) technique; the rate constant of
      DEE involving NB(*+) radical cation and NB neutral molecule is obtained.
      Advantages of the TR-MFE technique and its potential for measuring the short DEE
      times are discussed in detail.

PMID- 16599429
TI  - Extreme fluorescence sensitivity of some aniline derivatives to aqueous and
      nonaqueous environments: mechanistic study and its implication as a fluorescent
      probe.
AB  - Effects of solvent water on the photophysical properties of a series of meta- and
      para-substituted anilines have been investigated by means of time-resolved
      fluorescence, transient absorption, and photoacoustic measurements. Some aniline
      derivatives exhibit extremely short fluorescence lifetime (tau(f)) and small
      quantum yield (Phi(f)) in water (e.g., tau(f) = 45 ps and Phi(f) = 0.0019 for m
      cyanoaniline (m-ANCN) in H(2)O), which is in marked contrast with their much
      larger values in nonaqueous solvents (tau(f) = 7.3 ns and Phi(f) = 0.14 for m
      ANCN in acetonitrile). Photoacoustic and transient absorption measurements show
      that the remarkable fluorescence quenching of m-ANCN in water is attributed
      almost exclusively to fast internal conversion. The lifetime measurements of m
      ANCN in H(2)O/acetonitrile binary solvent mixtures reveal that the quenching is
      related to variation of hydrogen-bonding interactions between the amino group and
      water molecules and the conformational change of the amino group upon electronic
      excitation. Similar fluorescence quenching due to solvent water is also found for
      N-alkylated m-ANCNs. The drastic differences in the fluorescence intensity and
      lifetime of m-ANCNs under hydrophobic and hydrophilic environments and also the
      large solvent polarity dependence of the fluorescence band position suggest the
      possibility that they can be utilized as fluorescent probes for investigating the
      microenvironment of biological systems. In suspensions of human serum albumin
      (HSA) in water, remarkable enhancement of the fluorescence intensity and lifetime
      is observed for m-ANCN and its N-alkylated derivatives, demonstrating that m
      ANCNs can be a candidate for novel fluorescent probe with small molecular size.

PMID- 16599430
TI  - In search of excited-state proton transfer in the lumichrome dimer in the solid
      state: theoretical and experimental approach.
AB  - Quantum chemical density functional theory (DFT) calculations and spectral data
      were employed to investigate the possibility of the excited-state double proton
      transfer (ESDPT) in lumichrome crystals. The calculations in a lumichrome dimer
      predict a transfer of a proton in the first excited state, leading to a cation
      anion pair. The presently reported X-ray structure of 1,3-dimethyllumichrome and
      its complex solid-state luminescence indicate that also in this molecule
      intermolecular hydrogen bonds might be involved in the photophysics. The long
      wavelength emission in lumichrome crystals peaked at 530 nm is attributed to
      excited-state proton transfer, whereas a wider emission band in methylated
      lumichrome derivatives peaked at 560 nm is attributed to ions formed upon
      photoexcitation of the crystals.

PMID- 16599431
TI  - Theoretical study on the excited-state intramolecular proton transfer in the
      aromatic schiff base salicylidene methylamine: an electronic structure and
      quantum dynamical approach.
AB  - The proton-transfer dynamics in the aromatic Schiff base salicylidene methylamine
      has been theoretically analyzed in the ground and first singlet (pi,pi) excited
      electronic states by density functional theory calculations and quantum wave
      packet dynamics. The potential energies obtained through electronic calculations
      that use the time-dependent density functional theory formalism, which predict a
      barrierless excited-state intramolecular proton transfer, are fitted to a reduced
      three-dimensional potential energy surface. The time evolution in this surface is
      solved by means of the multiconfiguration time-dependent Hartree algorithm
      applied to solve the time-dependent Schrodinger equation. It is shown that the
      excited-state proton transfer occurs within 11 fs for hydrogen and 25 fs for
      deuterium, so that a large kinetic isotope effect is predicted. These results are
      compared to those of the only previous theoretical work published on this system
      [Zgierski, M. Z.; Grabowska, A. J. Chem. Phys. 2000, 113, 7845], reporting a
      configuration interaction singles barrier of 1.6 kcal mol(-1) and time reactions
      of 30 and 115 fs for the hydrogen and deuterium transfers, respectively,
      evaluated with the semiclassical instanton approach.

PMID- 16599432
TI  - The use of multidimensional Franck-Condon simulations to assess model
      chemistries: a case study on phenol.
AB  - Multidimensional Franck-Condon simulations of the dispersed fluorescence spectra
      of phenol generated with geometries obtained from the highly correlated post
      Hartree-Fock methods CASSCF, MRCI, and SACCI are presented. While the simulations
      based on CASSCF and MRCI optimized geometries are very similar to each other and
      fail to reproduce the experimentally measured intensities faithfully, the
      simulations obtained from SACCI optimized geometries are very close to the
      experimental spectra. The code developed for the multidimensional Franck-Condon
      simulations is described. It is shown that the integral storage problem common to
      the evaluation of multidimensional Franck-Condon integrals can be overcome by
      saving all quantities needed to disk. This strategy allows the code to run on
      computers with limited resources and is very well suited for application to
      molecules with a very large number of vibrational modes.

PMID- 16599433
TI  - Franck-Condon simulations of clusters: phenol-nitrogen.
AB  - Multidimensional Franck-Condon simulations of the resonance enhanced multiphoton
      ionization (REMPI) and mass-analyzed threshold ionization (MATI) spectra of
      phenol-nitrogen are obtained from CASSCF, MRCI, and SACCI optimized geometries.
      In the REMPI simulations, the results are unsatisfactory, as the transitions
      associated with intermolecular modes are widely underestimated and much less
      intense than those associated with intramolecular modes. Conversely, the
      simulations of the MATI spectra show a good similarity to experiment. The best
      simulations are obtained in both instances from the SACCI optimized geometries.
      Furthermore, the simulations suggest that the two most prominent Franck-Condon
      envelopes present in the MATI spectra are due to the sigma and sigma + ngamma'
      combination bands in accord with the assignments of the MATI spectra of the
      analogous phenol-carbon monoxide cluster.

PMID- 16599434
TI  - Conformational preferences and internal rotation in alkyl- and phenyl-substituted
      thiourea derivatives.
AB  - Potential energy surfaces (PES) for rotation about the N-C(sp(3)) or N-C(aryl)
      bond and energies of stationary points on PES for rotation about the C(sp(2))-N
      bond are reported for methylthiourea, ethylthiourea, isopropylthiourea, tert
      butylthiourea, and phenylurea, using the MP2/aug-cc-pVDZ method. Analysis of
      alkylthioureas shows that conformations, with alkyl groups cis to the sulfur
      atom, are more stable (by 0.4-1.5 kcal/mol) than the trans forms. All minima
      adopt anti configurations with respect to nitrogen pyramidalization, whereas syn
      configurations are not stationary points on the MP2 potential surface. In
      contrast, analysis of phenylthiourea reveals that a trans isomer in a syn
      geometry is the global minimum, whereas a cis isomer in an anti geometry is a
      local minimum with a relative energy of 2.7 kcal/mol. Rotation about the C(sp(2))
      N bond in alkyl and phenyl thioureas is slightly more hindered (9.1-10.2
      kcal/mol) than the analogous motion in the unsubstituted molecule (8.6 kcal/mol).
      The maximum barriers to rotation for the methyl, ethyl, isopropyl, tert-butyl,
      and phenyl substituents are predicted to be 1.2, 8.9, 8.6, 5.3, and 0.9 kcal/mol,
      respectively. Corresponding PESs are consistent with the experimental dihedral
      angle distribution observed in crystal structures. The results of the electronic
      structure calculations are used to benchmark the performance of the MMFF94 force
      field. Systematic discrepancies between MMFF94 and MP2 results were improved by
      modification of selected torsion parameters and one of the van der Waals
      parameters for sulfur.

PMID- 16599435
TI  - Conformational flexibility of L-alanine zwitterion determines shapes of Raman and
      Raman optical activity spectral bands.
AB  - Detailed analysis of Raman and Raman optical activity (ROA) of L-alanine
      zwitterion (ALAZW) revealed that shapes of the spectral bands are to a large
      extent determined by the rotation of the NH(3)(+), CO(2)(-), and CH(3) groups.
      Aqueous solution ALAZW spectra were measured down to 100 cm(-1) and compared to
      complex simulations based on ab initio (B3LYP/CPCM/6-31++G**) computations of
      molecular energies and spectral parameters. The bands exhibit different
      sensitivities to the motion of the rotating group; typically, for more
      susceptible bands the Raman signal becomes broader and the ROA intensity
      decreases. When these dynamical factors are taken into account in Boltzmann
      averaging of conformer contributions, simulated spectra not only better agree
      with the experiment, but shapes of the rotational potentials can be estimated.
      Effects of the molecular flexibility could be also demonstrated on differences in
      Raman spectra of the solution, crystalline, and glass (gellike) solid states of
      ALAZW. Experimental Raman and ROA spectra of four model dipeptides of different
      rigidities (Ala-Pro, Pro-Ala, Pro-Gly, and Gly-Pro) indicate that the broadening
      of spectral lines can be used as a general site-specific indicator of molecular
      rigidity or flexibility.

PMID- 16599436
TI  - Steric asymmetry in electron transfer from potassium atoms to oriented
      nitromethane (CH3NO2) molecules.
AB  - Electrons are transferred in collisions between potassium atoms and CH(3)NO(2)
      molecules that have been oriented in space prior to collision. The electron
      transfer produces K(+) ions, parent negative ions CH(3)NO(2)(-), and the fragment
      ions e(-), NO(2)(-), and O(-) in amounts that depend on the energy. The positive
      and negative ions are detected in coincidence by separate time-of-flight mass
      spectrometers at various collision energies for both CH(3)-end attack and NO(2)
      end attack. The steric asymmetry for electrons and CH(3)NO(2)(-) is essentially
      zero, but the steric asymmetry for NO(2)(-) shows that NO(2)(-) is formed mainly
      in CH(3)-end collisions. There is evidence that the electrons and NO(2)(-) have
      the same transient precursor, despite having different steric asymmetries. It
      appears likely that the precursor is formed by electron transfer mainly in
      collisions normal to the molecular axis leading to near zero steric asymmetry for
      the electron. This transient precursor can also eject an NO(2)(-) ion, which is
      more likely to be removed as KNO(2) salt when K(+) ions are near the NO(2) end of
      the molecule, with the result that CH(3)-end collisions seem to produce more
      NO(2)(-).

PMID- 16599437
TI  - Geometry and solvent dependence of the electronic spectra of the amide group and
      consequences for peptide circular dichroism.
AB  - The influence of geometry variations and solvent environment of N-methylacetamide
      on its energies and absorption intensities was systematically analyzed with the
      aid of the time-dependent density functional theory (TD DFT). Selective and often
      complicated reactions of individual electronic levels on the perturbations were
      found important for the resultant spectral profile. For example, the n-pi band
      position varied by tens of nanometers due to the C=O bond length oscillations,
      while it was rather unaffected by surrounding water. On the contrary, pi-pi type
      transition energies and intensities were broadly dispersed by the aqueous
      environment but exhibited a modest coordinate dependence. A simple electrostatic
      model used previously for absorption in the IR region (J. Chem. Phys. 2005, 122,
      144501) explained these changes only partially. Additionally, electronic transfer
      between the solute and the solvent had to be considered for faithful modeling of
      the ultraviolet light absorption. The inclusion of the environment and dynamics
      in the modeling then provided more accurate positions, intensities, and realistic
      inhomogeneous widths of spectral lines. These factors were found important for
      absorption and circular dichroism spectra of larger peptides and proteins. This
      was demonstrated with a combined DFT/coupled oscillator model providing principal
      features observed in electronic circular dichroism spectra of standard peptide
      conformations.

PMID- 16599438
TI  - The complexes between CH3OH and CF4. Infrared matrix isolation and theoretical
      studies.
AB  - The complex formed between methanol and tetrafluoromethane has been identified in
      argon and neon matrixes by help of FTIR spectroscopy. Three fundamentals (nu(OH),
      nu(FCF), and nu(CO)) were observed for the complex isolated in the two matrixes,
      and the OH stretch was red shifted in a neon matrix and blue shifted in an argon
      matrix with respect to the corresponding vibration of the methanol monomer. The
      theoretical studies of the structure and spectral characteristics of the
      complexes formed between CH(3)OH and CF(4) were carried out at the MP2 level of
      theory with the 6-311+G(2df,2pd) basis set. The calculations resulted in three
      stationary points from which two (I-1, I-2) corresponded to structures involving
      the O-H...F hydrogen bond and the third one (I-3) to the non-hydrogen-bonded
      structure. The topological analysis of the distribution of the charge density
      (AIM theory) confirmed the existence of the hydrogen bond in I-1, I-2 complexes
      and indicated weak interaction between the oxygen atom of CH(3)OH and three
      fluorine atoms of CF(4) in the I-3 complex. The comparison of the experimental
      and theoretical data suggests that in the matrixes only the non-hydrogen-bonded
      complex I-3 is trapped. The blue/red shift of the complex OH stretching vibration
      with respect to the corresponding vibration of CH(3)OH in argon/neon matrixes is
      explained by the different sensitivity of the complex and monomer vibrations to
      matrix material. The ab initio calculations performed for the ternary CH(3)OH
      CF(4)-Ar systems indicated a negligible effect of an argon atom on the binary
      complex frequencies.

PMID- 16599439
TI  - Formation of naphthalene, indene, and benzene from cyclopentadiene pyrolysis: a
      DFT study.
AB  - Four new reaction pathways for polycyclic aromatic hydrocarbon growth from
      cyclopentadiene pyrolysis are proposed and investigated using the B3LYP/6
      31G(d,p) level of theory. These pathways allow for the production of indene,
      naphthalene, and benzene through intramolecular addition, C-H beta-scission, and
      C-C beta-scission reaction mechanisms, respectively. Results show that the
      intramolecular addition channel is favored at low temperatures, and the C-H beta
      scission channel and the newly identified C-C beta-scission pathway become
      significant when the temperature increases. These results are in qualitative
      agreement with the experimental results previously obtained by this research
      group indicating that the main product at low temperature is indene, while
      benzene and naphthalene production dominate at the high-temperature end.

PMID- 16599440
TI  - Thermal decomposition mechanism of disilane.
AB  - Thermal decomposition of disilane was investigated using time-of-flight (TOF)
      mass spectrometry coupled with vacuum ultraviolet single-photon ionization (VUV
      SPI) at a temperature range of 675-740 K and total pressure of 20-40 Torr.
      Si(n)H(m) species were photoionized by VUV radiation at 10.5 eV (118 nm).
      Concentrations of disilane and trisilane during thermal decomposition of disilane
      were quantitatively measured using the VUV-SPI method. Formation of Si(2)H(4)
      species was also examined. On the basis of pressure-dependent rate constants of
      disilane dissociation reported by Matsumoto et al. [J. Phys. Chem. A 2005, 109,
      4911], kinetic simulation including gas-phase and surface reactions was performed
      to analyze thermal decomposition mechanisms of disilane. The branching ratio for
      (R1) Si(2)H(6) --> SiH(4) + SiH(2)/(R2) Si(2)H(6) --> H(2) + H(3)SiSiH was
      derived by the pressure-dependent rate constants. Temperature and reaction time
      dependences of disilane loss and formation of trisilane were well represented by
      the kinetic simulation. Comparison between the experimental results and the
      kinetic simulation results suggested that about 70% of consumed disilane was
      converted to trisilane, which was observed as one of the main reaction products
      under the present experimental conditions.

PMID- 16599441
TI  - Kinetics and mechanisms of the reactions of hydroxyl radicals and hydrated
      electrons with nitrosamines and nitramines in water.
AB  - Absolute rate constants for hydroxyl radical, *OH, and hydrated electron, e(aq)(
      ), reactions with low-molecular-weight nitrosamines and nitramines in water at
      room temperature were measured using the techniques of electron pulse radiolysis
      and transient absorption spectroscopy. The bimolecular rate constants obtained, k
      (M(-1) s(-1)), for e(aq)(-) and *OH reactions, respectively, were as follows:
      methylethylnitrosamine, (1.67 +/- 0.06) x 10(10) and (4.95 +/- 0.21) x 10(8);
      diethylnitrosamine, (1.61 +/- 0.06) x 10(10) and (6.99 +/- 0.28) x 10(8);
      dimethylnitramine, (1.91 +/- 0.07) x 10(10) and (5.44 +/- 0.20) x 10(8);
      methylethylnitramine, (1.83 +/- 0.15) x 10(10) and (7.60 +/- 0.43) x 10(8); and
      diethylnitramine, (1.76 +/- 0.07) x 10(10) and (8.67 +/- 0.48) x 10(8),
      respectively. MNP/DMPO spin-trapping experiments demonstrated that hydroxyl
      radical reaction with these compounds occurs by hydrogen atom abstraction from an
      alkyl group, while the reaction of the hydrated electron was to form a transient
      radical anion. The latter adduct formation implies that the excess electron could
      subsequently be transferred to regenerate the parent chemical, which would
      significantly reduce the effectiveness of any free-radical-based remediation
      effort on nitrosamine/nitramine-contaminated waters.

PMID- 16599442
TI  - Competitive diffusion-influenced reaction of a reactive particle with two static
      sinks.
AB  - An investigation into the kinetics of reaction between a diffusing particle and a
      system of two static spherical sinks is presented. The backward diffusion
      equation is solved for the probability of reaction with each sink, using both
      absorbing and radiation boundary conditions. The rate constants for each reaction
      are also calculated. The reactivity of the sinks is shown to be subadditive, and
      if the sinks are asymmetric the less reactive sink is more strongly affected by
      the competition. Competitive effects are found to be modeled adequately by using
      effective reaction radii. The IRT method is shown to have serious defects for
      such a system because of the correlation of the two sinks. An application to the
      reaction of OH radicals with thymidine is presented.

PMID- 16599443
TI  - Kinetics and mechanism of the oxidation of sulfite by chlorine dioxide in a
      slightly acidic medium.
AB  - The sulfite-chlorine dioxide reaction was studied by stopped-flow method at I =
      0.5 M and at 25.0 +/- 0.1 degrees C in a slightly acidic medium. The
      stoichiometry was found to be 2 SO(3)(2-) + 2.ClO(2) + H(2)O --> 2SO(4)(2) (-) +
      Cl(-) + ClO(3)(-) + 2H(+) in *ClO(2) excess and 6SO(3)(2-) + 2*ClO(2) -->
      S(2)O(6)(2-) + 4SO(4)(2-) + 2Cl(-) in total sulfite excess ([S(IV)] = [H(2)SO(3)]
      + [HSO(3)(-)] + [SO(3)(2-)]). A nine-step model with four fitted kinetic
      parameters is suggested in which the proposed adduct *SO(3)ClO(2)(2-) plays a
      significant role. The pH-dependence of the kinetic traces indicates that SO(3)(2
      ) reacts much faster with *ClO(2) than HSO(3)(-) does.

PMID- 16599444
TI  - Quantum chemical study of the photocoloration reaction in the napthoxazine
      series.
AB  - Ab initio and semiempirical quantum mechanical calculations were performed to
      study the electronic spectra of spiroxazine photochromic compounds as well as the
      corresponding photoisomers. Ground-state geometries were optimized based on
      density functional theory (DFT). Excitation energies of the different forms were
      calculated using the time-dependent density functional theory (TD-DFT) method.
      Semiempirical calculations including configuration interactions were performed to
      detail the mechanism of ring opening in excited states. On the basis of the
      obtained potential energy profile, a complete mechanism of photocoloration able
      to clarify some experimental findings is provided. A correlation of the
      experimental quantum yield of photocoloration with the calculated properties as a
      function of substituent effects is proposed.

PMID- 16599445
TI  - The possible covalent nature of N-H...O hydrogen bonds in formamide dimer and
      related systems: an ab initio study.
AB  - The N-H...O hydrogen bonds are analyzed for formamide dimer and its simple
      fluorine derivatives representing a wide spectrum of more or less covalent
      interactions. The calculations were performed at the MP2/6-311++G(d,p) level of
      approximation. To explain the nature of such interactions, the Bader theory was
      also applied, and the characteristics of the bond critical points (BCPs) were
      analyzed: the electron density at BCP and its Laplacian, the electron energy
      density at BCP and its components, the potential electron energy density, and the
      kinetic electron energy density. These parameters are used to justify the
      statement that some of the interactions analyzed are partly covalent in nature.
      An analysis of the interaction energy components for the systems considered
      indicates that the covalent character of the hydrogen bond is manifested by a
      markedly increased contribution of the delocalization term relative to the
      electrostatic interaction energy. Moreover, the ratio of stabilizing the
      delocalization/electrostatic contributions grows linearly with the decreasing
      lengths of the hydrogen bond.

PMID- 16599446
TI  - Theoretical study of endohedral C36 and its dimers.
AB  - It is found that atoms of lithium and carbon can be encapsulated in C(36) on the
      basis of the calculation of their encapsulation energies using density functional
      theory. Specifically, they can be encapsulated in C(36) better than in C(60)
      despite the smaller (70%) cavity size of the former. In C@C(36), the encapsulated
      carbon atom forms covalent bonds with the carbon atoms of the cage, which is in
      contrast with the case of N@C(60.) Two isomers are expected to be in an
      equilibrium which involves spin quenching and generation. Li@C(36) and C@C(36)
      are expected to exist in the form of dimers with nonendohedral fullerenes, i.e.,
      as Li@C(36)-C(36) and C@C(36)-C(36). Three stable isomers were found for the
      former (A, B, and C). Equilibrium between A and C as well as that between B and C
      is accompanied by spin transfer between two fullerene units, while that between A
      and B is not. The two stable isomers in C@C(36)-C(36) form an equilibrium
      accompanied by spin quenching and generation, allowing the dimer to be
      potentially useful for molecular devices.

PMID- 16599447
TI  - Revisiting the structure of (LiCH3)n aggregates using Car-Parrinello molecular
      dynamics.
AB  - The theoretical study of (LiMe)(n) aggregates using Car-Parrinello molecular
      dynamics was undertaken. With respect to a quantum chemical static treatment,
      this approach furnishes supplementary information about the structural
      parameters. Equilibrium structures are indeed stable to ca. 300 K, provided the
      methyl groups in the aggregates are considered to rotate essentially freely. The
      Li-C distance depends on the coordination number of Li and not so much on the
      degree of aggregation. Finally, above 650 K, the cubic LiCH(3) tetramer (which is
      energetically favored) undergoes an entropy-driven rearrangement to a planar
      structure.

PMID- 16599448
TI  - Copper cation interactions with biologically essential types of ligands: a
      computational DFT study.
AB  - This work presents a systematic theoretical study on Cu(I) and Cu(II) cations in
      variable hydrogen sulfide-aqua-ammine ligand fields. These ligands model the
      biologically most common environment for Cu ions. Molecular structures of the
      complexes were optimized at the density functional theory (DFT) level. Subsequent
      thorough energy analyses revealed the following trends: (i) The ammine complexes
      are the most stable, followed by those containing the aqua and hydrogen sulfide
      ligands, which are characterized by similar stabilization energies. (ii) The most
      preferred Cu(I) coordination number is 2 in ammine or aqua ligand fields. A
      qualitatively different binding picture was obtained for complexes with H(2)S
      ligands where the 4-coordination is favored. (iii) The 4- and 5-coordinated
      structures belong to the most stable complexes for Cu(II), regardless of the
      ligand types. Vertical and adiabatic ionization potentials of Cu(I) complexes
      were calculated. Charge distribution (using the natural population analysis (NPA)
      method) and molecular orbital analyses were performed to elucidate the nature of
      bonding in the examined systems. The results provide in-depth insight into the Cu
      binding properties and can be, among others, used for the calibration of
      bioinorganic force fields.

PMID- 16599449
TI  - Nonclassical carbocations as C-H hydrogen bond donors.
AB  - Computed [B3LYP/6-31+G(d,p) and MP2/6-31+G(d,p)] structures and binding energies
      for complexes of nonclassical cations (carbonium ions) with ammonia, in the gas
      phase and several solvents, are described. Overall, nonclassical cations are
      found to be competent C-H hydrogen bond donors. The potential relevance of the C
      H...N interactions holding the carbocation.amine complexes together for enzyme
      catalyzed terpenoid synthesis is discussed.

PMID- 16599450
TI  - Theoretical study on the second-order nonlinear optical properties of asymmetric
      spirosilabifluorene derivatives.
AB  - The equilibrium geometries of four asymmetric spirosilabifluorene derivatives are
      optimized by means of the DFT/B3LYP method with the 6-31G* basis sets in this
      paper. On the basis of the optimized structures, the electronic structure and
      second-order nonlinear optical properties are calculated by using time-dependent
      density-functional theory (TDDFT) based on the 6-31G* level combined with the sum
      over-states (SOS) method. The results show that these compounds possess
      remarkably larger molecular second-order polarizabilities than typical
      organometallic and organic compounds, and replacement of a carbon atom with
      nitrogen within the conjugated substituent has a great influence on the second
      order nonlinear optical properties. Analysis of the main contributions to the
      second-order polarizability suggests that charge transfer from the z-axis
      directions plays a key role in the nonlinear optical response. These compounds
      have a possibility to be excellent second-order nonlinear optical (NLO) materials
      from the standpoint of large beta values, small dipole moment, high transparency,
      and small dispersion behaviors.

PMID- 16599451
TI  - Effects of intermolecular vibrational coupling and liquid dynamics on the
      polarized Raman and two-dimensional infrared spectral profiles of liquid N,N
      dimethylformamide analyzed with a time-domain computational method.
AB  - A time-domain method for calculating polarized Raman and two-dimensional infrared
      (2D-IR) spectra that includes the effects of both the diagonal frequency
      modulations (of individual molecules in the system) and the off-diagonal
      (intermolecular) vibrational coupling is presented and applied to the case of the
      amide I band of liquid N,N-dimethylformamide. It is shown that the effect of the
      resonant off-diagonal vibrational coupling and the resulting delocalization of
      vibrational modes is clearly seen as the noncoincidence effect in the polarized
      Raman spectrum and some spectral features (especially as asymmetric intensity
      patterns) in the 2D-IR spectra. The type of 2D-IR spectra (concerning the
      polarization condition) most appropriate for observing this effect is discussed.
      On the basis of the agreement between the observed and calculated band profiles
      of the polarized Raman spectrum, the time dependence of the transient IR
      absorption anisotropy is also calculated. The method of evaluating the extent of
      delocalization of vibrational modes that is relevant to the features of these
      optical signals in the time and frequency domains is discussed. The nature of the
      molecular motions (concerning the liquid dynamics) that are effective on the
      diagonal frequency modulations is also examined.

PMID- 16599452
TI  - An investigation of hydrogen-bonding effects on the nitrogen and hydrogen
      electric field gradient and chemical shielding tensors in the 9-methyladenine
      real crystalline structure: a density functional theory study.
AB  - Hydrogen-bonding effects in the real crystalline structure of 9-methyladenine, 9
      MA, were studied using calculated electric field gradient, EFG, and chemical
      shielding, CS, tensors for nitrogen and hydrogen nuclei via density functional
      theory. The calculations were carried out at the B3LYP and B3PW91 levels with the
      6-311++G basis set via the Gaussian 98 package. Nuclear quadrupole coupling
      constants, C(Q), and asymmetry parameters, eta(Q), are reported for (14)N and
      (2)H. The chemical shielding anisotropy, Deltasigma, and chemical shielding
      isotropy, sigma(iso), are also reported for (15)N and (1)H. The difference
      between the calculated parameters of the monomer and heptameric layer-like
      cluster 9-MA shows how much H-bonding interactions affect the EFG and CS tensors
      of each nucleus. This result indicates that N(10) (imino nitrogen) has a major
      role in H-bonding interactions, whereas that of N(9) is negligible. There is good
      agreement between the present calculated parameters and reported experimental
      data. Although some discrepancies were observed, this could be attributed to the
      different conditions which were applied for calculation and the experiments.

PMID- 16599453
TI  - QTAIM charge-charge flux-dipole flux models for the infrared fundamental
      intensities of the fluorochloromethanes.
AB  - The molecular dipole moments, their derivatives, and the fundamental IR
      intensities of the fluoro-, chloro-, and fluorochloromethanes are determined from
      QTAIM atomic charges and dipoles and their fluxes at the MP2/6-311++G(3d,3p)
      level. Root-mean-square (rms) errors of 0.01 D and 5.6 km mol(-1) are found for
      the dipole moments and fundamental IR intensities calculated using QTAIM
      parameters when compared with those obtained directly from the MP2/6-311++(3d,3p)
      calculations and 0.04 D and 23.1 km mol(-1) when compared with the experimental
      values. Charge, charge flux, and dipole flux contributions are calculated for all
      the normal vibrations of these molecules. A large negative correlation
      coefficient of -0.92 is calculated between the charge flux and dipole flux
      contributions and indicates that electron transfer from one side of the molecule
      to the other during vibrations is accompanied by relaxation with electron density
      polarization in the opposite direction. The CF, CCl, and CH stretching normal
      modes of these molecules are shown to have characteristic sets of charge, charge
      flux, and dipole flux contributions. Although the FCF and ClCCl deformation
      normal modes can also be discriminated from one another based on the sizes and
      signs of these contributions, some HCH deformations have contributions that are
      similar to those for some of the ClCCl deformations.

PMID- 16599454
TI  - Density functional investigation of high-spin XY (X = Cr, Mo, W and Y = C, N, O)
      molecules.
AB  - The performance of a density functional theory approach in calculating the
      equilibrium bond length, dipole moment, and harmonic vibrational frequency in a
      series of group 6 (Cr, Mo, W) transition metal-containing diatomic molecules is
      evaluated. Using flexible basis sets comprised of Slater type functions, a wide
      range of exchange-correlation functionals is investigated. Comparing with known
      experimental values and published results from high-level theoretical
      calculations, the most suitable functional form is selected. The importance of
      relativistic effects is checked, and predictions are made for several unknown
      dipole moments. The best agreement with experimental parameters is obtained when
      using a general gradient approximation, while special and hybrid functional forms
      give less accurate results.

PMID- 16599455
TI  - Spectroscopy of the cyano radical in an aqueous environment.
AB  - The effect of bulk water on the B (2)Sigma(+) <-- X (2)Sigma(+) and A (2)Pi <-- X
      (2)Sigma(+) electronic transitions of the cyano radical is investigated. First,
      the cyano radical-water dimer is characterized to understand the nature of the
      interactions and parametrize molecular mechanics (MM) potentials. The carbon
      atom, which hosts the unpaired electron, is found to have a Lennard-Jones radius
      smaller than typical force fields values. Classical molecular dynamics (MD) is
      then used to sample water configurations around the radical, employing two sets
      of MM parameters for the cyano radical and water. Subsequently, vertical
      excitation energies are calculated using time-dependent density functional theory
      (TD-DFT) and equation-of-motion coupled-cluster with single and double
      substitutions (EOM-CCSD). The effect of water is modeled by point charges used in
      the MD simulations. It is found that both bands blue-shift with respect to their
      gas phase position; the magnitude of the shift is only weakly dependent on the
      method and the MM parameter set used. The calculated shifts are analyzed in terms
      of the solute-solvent interactions in the ground and excited states. Significant
      contributions come from valence repulsion and electrostatics. Consequences for
      experiments on ICN photodissociation in water are discussed.

PMID- 16599456
TI  - High-spin radical cations of a dendritic oligoarylamine.
AB  - A new dendritic oligoarylamine, N,N,N',N',N",N"-hexakis[4-(di-4
      anisylamino)phenyl]- 1,3,5-benzenetriamine (BTA) 2, which contains a 1,3,5
      benzenetriamine molecular unit as an potential precursor of a high-spin molecule
      and three oligoarylamine moieties as spin-carrying units surrounding the core
      BTA, has been prepared by the sequential palladium-catalyzed amination reactions.
      The redox property has been investigated by cyclic voltammetry, and the highly
      charged states up to the hexacation are accessible to 2. The polycationic high
      spin species have been generated by stepwise chemical oxidation, and the
      electronic structures have been examined in detail by the continuous wave (CW)
      and pulsed ESR spectroscopy in comparison with the previously studied 1. The
      pulsed ESR technique enabled us to determine the definite spin multiplicity of
      the generated polycationic species of 2. It was confirmed that the dominant
      oxidized species observed by the two- and three-electron oxidations were assigned
      to the spin triplet 2(2+) and the spin quartet 2(3+), respectively. Moreover,
      these high-spin polycationic species turned out to be far more stable as compared
      to 1, and the isolation of 2(3+) as the SbCl(6)(-) salt has been accomplished.
      The temperature dependence of the magnetic susceptibility for the 2(3+)(SbCl(6)(
      ))(3) salt revealed that the intramolecular ferromagnetic interaction exists in
      2(3+), and moreover, the trication 2(3+) was found to be deformed in the solid
      state.

PMID- 16599457
TI  - Calculation of solvation free energy from quantum mechanical charge density and
      continuum dielectric theory.
AB  - We have combined ultrasoft pseudopotential density functional theory utilizing
      plane wave basis with a Poisson-Boltzmann/solvent-accessible surface area (PB/SA)
      model to calculate the solvation free energy of small neutral organic compounds
      in water. The solute charge density obtained from density functional theory was
      directly used in solving the Poisson-Boltzmann equation to obtain the reaction
      field. The polarized electronic wave function of the solute in the solvent was
      solved by including the reaction field in the density functional Hamiltonian. The
      quantum mechanical and Poisson-Boltzmann equations were solved self-consistently
      until the charge density and reaction field converged. Using the solute charge
      density directly instead of a point-charge representation permitted asymmetric
      distortion and spreading out of the electron cloud. Because the electron density
      could leave the van der Waals surface to penetrate into the high-dielectric
      solvent, the reaction field generated by this density was generally smaller than
      that obtained by using the point-charge representation. In applying this model to
      calculate the solvation free energy of 31 small neutral organic molecules
      spanning a range of 25 kcal/mol, we obtained a root-mean-square error of only 1.3
      kcal/mol if we allowed one adjustable parameter to shift the calculated solvation
      free energy.

PMID- 16599458
TI  - Vibrational spectroscopy of reduced ReI complexes of 1,10-phenanthroline and
      substituted analogues.
AB  - IR spectroscopy in concert with DFT calculations and resonance Raman
      spectroelectrochemistry has been used to identify the molecular orbital nature of
      the singly occupied molecular orbital (SOMO) in reduced [Re(CO)(3)Cl(L)] and
      [Re(CO)(3)(4-Mepy)(L)](+) complexes, where L = 1,10-phenanthroline and its 4,7
      diphenyl- and 3,4,7,8-tetramethyl-substituted analogues. The SOMO of each reduced
      species considered was found to be of b(1) symmetry, rather than the close lying
      orbital of a(2) symmetry (within a C(2)(v)() symmetry description of the
      phenanthroline moiety). This was deduced in a number of ways. First, the average
      carbonyl band force constants (Deltak(av) = k(av){reduced complex} - k(av){parent
      complex}) range from -57 to -41 N m(-1) for the series of compounds studied. The
      value of Deltak(av) relates to the extent of orbital overlap between the ligand
      MO and the metal dpi MO. These values are consistent with population of a b(1) MO
      because the wave function amplitude at the chelating nitrogens for this MO is
      significantly greater than that for a(2) MO. Second, calculations on singly
      reduced [Re(CO)(3)(4-Mepy)(phen)](+) and [Re(CO)(3)(4-Mepy)(tem)](+) predict
      population of a b(2) SOMO. The spectra predicted for these species are in close
      agreement with the vibrational spectroscopic data; for the IR data the shifts in
      the CO bands are predicted to 6 cm(-1) and the mean absolute deviation between
      calculated and measured Raman bands was found to be 10 cm(-1).

PMID- 16599459
TI  - A theoretical study on the third-order nonlinear optical properties of pi
      conjugated linear porphyrin arrays.
AB  - By using the Pariser-Parr-Pople (PPP) theory, the second hyperpolarizabilities
      (gamma) have been calculated for various pi-conjugated porphyrin arrays including
      "porphyrin tapes": the meso-beta doubly linked porphyrin array Dn and the meso
      meso, beta-beta, beta-beta triply linked array Tn. The validity of the PPP theory
      is checked via a comparison with both the ab initio Hartree-Fock and the B3LYP
      theories in the case of porphyrin monomers and dimers. It is found that Dn and
      especially Tn exhibit much more remarkable evolution of gamma/n along with an
      increasing number of porphyrin units n compared with the butadiyne-bridged array,
      Yn. As a result, the static third-order susceptibilities chi((3)) of Dn and Tn
      are expected to be 1 and 3 orders of magnitude larger than that of Yn in the
      limit n --> infinity, and these advantages of porphyrin tapes become more
      prominent by taking into account geometrical relaxations of porphyrin units in
      the arrays. The structure-property relationship in various conjugated polymers
      including porphyrin arrays is interpreted on the basis of the scaling behaviors
      of chi((1)) and chi((3)) with the effective conjugation length (ECL) as well as
      the reciprocal HOMO-LUMO energy gap (1/E(g)). In particular, from the master plot
      of chi((3)) (and even chi((1))) versus 1/E(g), the pi-conjugation of Tn is noted
      to indeed be exceptional, because its large susceptibilities cannot be expected
      from the scaling behavior of ordinary one-dimensional conjugated systems. We also
      point out that the theory of scaling relationship, chi((3)) approximately
      1/E(g)(x)(), is significantly improved by taking into account electron-electron
      interactions based on the comparison with experiments.

PMID- 16599460
TI  - Cationic germanium fluorides: a theoretical investigation on the structure,
      stability, and thermochemistry of GeFn/GeFn+ (n = 1-3).
AB  - The structure, harmonic frequencies, enthalpies of formation, and dissociation
      energies of the GeF(n)(+) cations (n = 1-3) and of their neutral counterparts
      GeF(n) have been investigated at the MP2 and CCSD(T) levels of theory and
      discussed in connection with previous experimental and theoretical data. The
      CCSD(T,full)/cc-pVTZ-optimized geometries and MP2(full)/6-311G(d) harmonic
      frequencies are 1.744 A and 668.0 cm(-1) for GeF((2)Pi), 1.670 A and 798.6 cm(-1)
      for GeF(+)((1)Sigma(+)), 1.731 A/97.4 degrees and 267.0 (a(1))/673.1 (b(2))/690.6
      (a(1)) cm(-1) for GeF(2)(C(2)(v),(1)A(1)), 1.666 A/116.9 degrees and 202.3
      (a(1))/769.6 (a(1))/834.6 (b(2)) cm(-1) for GeF(2)(+)(C(2)(v),(2)A(1)), 1.706
      A/112.2 degrees and 214.4 (e)/273.1 (a(1))/699.6 (a(1))/734.1 (e) cm(-1) for
      GeF(3)(C(3)(v),(2)A(1)), and 1.644 A and 211.4 (e')/229.9 (a(2)' ')/757.4
      (a(1)')/879.3 (e') cm(-1) for GeF(3)(+)(D(3)(h),(1)A(1)). These calculated values
      are in excellent agreement with the experimental data reported for GeF, GeF(+),
      and GeF(2), and should be therefore of good predictive value for the still
      unexplored GeF(2)(+), GeF(3), and GeF(3)(+). The comparison of the
      CCSD(T,full)/cc-pVTZ enthalpies of formation at 298.15 K, -11.6 (GeF), -125.9
      (GeF(2)), -180.4 (GeF(3)), 158.4 (GeF(+)), 134.1 (GeF(2)(+)), and 44.8
      (GeF(3)(+)) kcal mol(-1), with the available experimental data, especially for
      the cations, shows discrepancies which suggest the need for novel and more
      refined measurements. On the other hand, the computed adiabatic ionization
      potentials of GeF, 7.3 eV, GeF(2), 11.2 eV, and GeF(3), 9.7 eV, are in good
      agreement with the available experimental estimates.

PMID- 16599461
TI  - Theoretical studies on dications and trications of FH, ClH, and BrH. Properties
      of the bound 1(5)sigma- states. Electron-spin g-factors and fine/hyperfine
      constants of the metastable X3Sigma- states of ClH2+ and BrH2+.
AB  - This theoretical study reports calculations on the fine and hyperfine structure
      parameters of the metastable X(3)Sigma(-)(sigma(2)pi(2)) state of ClH(2+) and
      BrH(2+). Data on the repulsive FH(2+) system are also included for comparison
      purposes. The hyperfine structure (hfs) coupling constants for magnetic (A(iso),
      A(dip)) and quadrupole (eQq) interactions are evaluated using B3LYP, MP4SDQ,
      CCSD, and QCISD methods and several basis sets. The fine structure (fs) constants
      (zero-field splitting lambda and spin-rotation coupling gamma) and electron-spin
      magnetic moments (g-factor) are evaluated in 2nd-order perturbation theory using
      multireference CI (MRCI) wave functions. Our calculations find for (35)Cl of
      ClH(2+) A(iso)/A(dip) = 110/-86 MHz; eQq(0) = -59 MHz; 2lambda = 20.4 cm(-1); g(
      perpendicular)(v = 0) = 2.02217; and gamma = -0.31 cm(-1) (to be compared with
      the available experimental A(iso)/A(dip)= 162/-30 MHz). For (79)BrH(2+), the
      corresponding values are 300/-400 MHz; 368 MHz; 362.6 cm(-1); 2.07302; and -0.98
      cm(-1) (experimental 2lambda = 445(+/-80) cm(-1)). We find g(
      perpendicular)(ClH(2+)) to increase by about 0.0054 between v = 0 and 2, whereas
      the experimental effective g( perpendicular) changes drastically with vibrational
      excitation. Nuclear quadrupole coupling constants for halogen atoms X are found
      to be as large as corresponding A(dip)(X)'s, indicating that both terms may have
      to be included in the Hamiltonian used to interpret XH(2+) hyperfine spectra. A
      novel finding relates to the bound character of the 1(5)Sigma(-)(sigmapi(2)sigma)
      state in FH(2+), as already known for ClH(2+) and BrH(2+), but having a deeper
      potential well D(e) approximately 4,000 cm(-1) (versus 1,000 cm(-1) in the
      heavier radicals). Vertical ionization potentials for formation of XH(3+)
      trications are also discussed.

PMID- 16599462
TI  - Investigation of the influence of hydroxy groups on the radical scavenging
      ability of polyphenols.
AB  - Recently, O-H bond dissociation enthalpies (BDEs) have been successfully used to
      express the free radical scavenging ability of polyphenolic antioxidants. In this
      work, the BDEs of phenol, catechol, resorcinol, hydroquinone, pyrogallol,
      phloroglucinol, 1,2,4-benzenetriol, and 5-hydroxypyrogallol have been calculated
      at B3LYP/6-311G++(3df, 3pd) and used to elucidate the effect of OH groups.
      Increasing the number of OH groups in the adjacent (vicinal) position decreases
      the BDE of phenols. Increasing the number of O-H groups in the alternative
      position C(1,3) as in resorcinol and C(1,3,5) as in phloroglucinol does not show
      any notable change in the BDEs when compared to that of OH in C(1) as in phenol.
      5-Hydroxypyrogallol has the smallest BDE (250.3 kJ mol(-1)) followed by
      pyrogallol (289.4 kJ mol(-1)), then 1,2,4-benzenetriol (294.8 kJ mol(-1)), and
      then catechol (312.8 kJ mol(-1)). Overall, our results indicated that the
      presence of ortho and para hydroxy groups reduces the BDEs. An intramolecular
      hydrogen bond (IHB) develops due to the ortho arrangement of OH's and plays a
      dominant role in decreasing the BDEs. This key study on phenols showed that the
      reactive order of OH position in the benzene ring is the following: 5
      hydroxypyrogallol > pyrogallol > 1,2,4-benzenetriol > catechol > hydroquinone >>
      phenol approximately resorcinol approximately phloroglucinol.

PMID- 16599463
TI  - Simulations of liquid ammonia based on the combined quantum mechanical/molecular
      mechanical (QM/MM) approach.
AB  - Two combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics
      simulations, namely, HF/MM and B3LYP/MM, have been performed to investigate the
      local structure and dynamics of liquid ammonia. The most interesting region, a
      sphere containing a central reference molecule and all its nearest surrounding
      molecules (first coordination shell), was treated by the Hartree-Fock (HF) and
      hybrid density functional B3LYP methods, whereas the rest of the system was
      described by the classical pair potentials. On the basis of both HF and B3LYP
      methods, it is observed that the hydrogen bonding in this peculiar liquid is
      weak. The structure and dynamics of this liquid are suggested to be determined by
      the steric packing effects, rather than by the directional hydrogen bonding
      interactions. Compared to previous empirical as well as Car-Parrinello (CP)
      molecular dynamics studies, our QM/MM simulations provide detailed information
      that is in better agreement with experimental data.

PMID- 16599464
TI  - Is the hypothiocyanite anion (OSCN)- the major product in the peroxidase
      catalyzed oxidation of the thiocyanate anion (SCN)-? A joint experimental and
      theoretical study.
AB  - The hypothiocyanate anion (OSCN)(-) is reported to be a major product of the
      lactoperoxidase/H(2)O(2)/(SCN)(-) system, and this anion is proposed to have
      significant antimicrobial properties. The collision induced (CID) negative ion
      mass spectrum of "(OSCN)(-)" has been reported: there is a pronounced parent
      anion at m/z 74, together with fragment anions at m/z 58 (SCN)(-) and 26 (CN)(-).
      These fragment anions are consistent with structure (OSCN)(-). However there is
      also a lesser peak at m/z 42 (OCN(-) or CNO(-)) in this spectrum which is either
      formed by rearrangement of (OSCN)(-) or from an isomer of this anion. The current
      theoretical investigation of (OSCN)(-) and related isomers, together with the
      study of possible rearrangements of these anions, indicates that ground-state
      singlet (OSCN)(-) is a stable species and that isomerization is unlikely. The
      three anions (OSCN)(-), (SCNO)(-), and (SNCO)(-) have been synthesized (in the
      ion source of a mass spectrometer) by unequivocal routes, and their structures
      have been confirmed by a consideration of their collision induced (negative ion)
      and charge reversal (positive ion) mass spectra. The CID mass spectrum of (SCNO)(
      ) shows formation of m/z 42 (CNO(-)), but the corresponding spectra of (OSCN)(-)
      or (SNCO)(-) lack peaks at m/z 42. Combined theoretical and experimental data
      support earlier evidence that the hypothiocyanite anion is a major oxidation
      product of the H(2)O(2)/(SCN)(-) system. However, the formation of m/z 42 in the
      reported CID spectrum of "(OSCN)(-)" does not originate from (OSCN)(-) but from
      another isomer, possibly (SCNO)(-).

PMID- 16599465
TI  - Determination of ionic liquids solvent properties using an unusual probe: the
      electron donor-acceptor complex between 4,4'-bis(dimethylamino)-benzophenone and
      tetracyanoethene.
AB  - Michler's ketone (MK) and tetracyanoethene (TCNE) may be used as a UV-vis probe
      to investigate the solvent properties of ionic liquids (ILs). In molecular
      solvents, MK and TCNE give an electron donor-acceptor (EDA) complex, a
      zwitterionic species or a radical ion pair, depending on the aprotic or protic
      nature of the solvent and on its ionizing power. In agreement with the behavior
      observed in aprotic solvents, only the EDA complex was detected in ILs bearing
      low donor anions (beta < 0.7). The formation constant determined in
      [bmim][Tf(2)N] (K(c) = 5.6 (0.5) M(-1)) is similar to that measured in 1,2
      dichloroethane at 25 degrees C. The visible absorption maximum (nu(max,CTC)) of
      the EDA complex is quantitatively described by a multiple correlation using the
      Kamlet-Taft pi, beta, and alpha parameters of the solvents. The H-bond donating
      capacity of ILs is not sufficient to determine the transformation of the EDA
      complex into the zwitterionic species, but the Kamlet-Taft alpha parameter seems
      to affect the position of the absorption band. The high ionization power of ILs,
      moreover, favors the slow dissociation of the EDA complex into its corresponding
      radical ion pair; this behavior generally characterizes highly polar and highly
      ionizing protic solvents, such as TFE and HFI. Finally, since the formation of
      the EDA complex is strongly affected by the presence of impurities, traces of
      nucleophiles (chloride or amines) or water may be easily detected through the
      change of the solution color.

PMID- 16599467
TI  - Amphiphilic character of the hydrated proton in methanol-water solutions.
AB  - The hydrated proton was studied in methanol-water solutions of varying methanol
      concentrations using the multistate empirical valence bond simulation method.
      Amphiphile-like behavior of the hydrated proton was noted from its anisotropic
      association with the methanol methyl groups. Molecular length immiscibility was
      also characterized through the enumeration of water and protonated water
      clusters. Excess proton diffusion was calculated across the varying methanol
      concentrations and found to be in good agreement with experiment after correcting
      for nuclear quantum effects.

PMID- 16599468
TI  - Marangoni effect reverses coffee-ring depositions.
AB  - We show here both experimentally and theoretically that the formation of "coffee
      ring" deposits observed at the edge of drying water droplets requires not only a
      pinned contact line but also suppression of Marangoni flow. For simple organic
      fluids, deposition actually occurs preferentially at the center of the droplet,
      due to a recirculatory flow driven by surface-tension gradients produced by the
      latent heat of evaporation. The manipulation of this Marangoni flow in a drying
      droplet should allow one in principle to control and redirect evaporation-driven
      deposition and assembly of colloids and other materials.

PMID- 16599469
TI  - Room-temperature kinetics of short-chain alkanethiol film growth on Ag(111) from
      the vapor phase.
AB  - We have used time-of-flight (TOF) direct recoiling spectroscopy (DRS) to follow
      propanethiol adsorption at 300 K from the vapor phase on an Ag(111) surface, for
      exposures ranging from 10(-1) to 10(5) L. Results show that the adsorption
      proceeds with changes in the sticking coefficient, consistent with at least three
      phases. At low exposures, the alkanethiol molecules adsorb with high probability
      at defect sites, followed by a slower growth mode that essentially covers the
      whole surface. A third change in the sticking coefficient is associated with the
      final saturation stage, corresponding to a thicker layer related to molecules in
      a more upright orientation. The adsorption kinetics for hexanethiol is similar to
      that of propanethiol but taking place at higher rates, stressing the importance
      of the hydrocarbon chain length in the growth process. ISS-TOF measurements
      during thermal desorption show that most of the C, H, and S go away together,
      suggesting that the molecules adsorb and desorb from flat regions without S-C
      bond cleavage. Fitting the desorption maximum at 450 K with a first-order
      desorption curve gives a desorption energy of 1.43 eV. A small final S content
      that is correlated with the initial Ag(111) surface roughness is observed after
      desorption.

PMID- 16599470
TI  - Kinetics of cross-nucleation between polymorphs.
AB  - We report the first kinetic measurement of cross-nucleation between polymorphs, a
      newly discovered phenomenon important to the theory and control of
      crystallization. d-Mannitol crystallized from its melt first as the least stable
      delta polymorph and then as the second least stable alpha polymorph, with alpha
      nucleating on delta. The kinetics of cross-nucleation was determined from the
      frequencies of alpha nuclei appearing on delta spherulites, the distances between
      alpha and delta nuclei, and the growth rate of the delta spherulite. The presence
      of poly(vinylpyrrolidone), a noncrystallizing, melt-miscible additive, increased
      the rate of cross-nucleation.

PMID- 16599471
TI  - Room temperature fabrication of hollow ZnS and ZnO architectures by a sacrificial
      template route.
AB  - Hollow ZnS and ZnO architectures are fabricated by employing
      Zn(5)(CO(3))(2)(OH)(6) microspheres as the sacrificial template.
      Zn(5)(CO(3))(2)(OH)(6) microspheres can be effectively converted into the
      core/shell structured ZnO/ZnS composites (in the Na(2)S solution) and hollow ZnO
      architectures (in the KOH solution), by a spontaneous ion replacement reaction at
      room temperature. Removing the core by the KOH treatment of core/shell structured
      ZnO/ZnS, hollow ZnS spheres with different shell thicknesses can be effectively
      achieved. The obtained hollow ZnO architectures exhibit unique geometrical
      shapes, and their walls are composed of nanocrystals, which are connected to each
      other to form their hemispherical or circular shape. A possible formation process
      from Zn(5)(CO(3))(2)(OH)(6) microspheres to core/shell structured ZnO/ZnS
      composites is proposed by arresting a series of intermediate morphologies.

PMID- 16599472
TI  - A molecular dynamics investigation of hydrolytic polymerization in a metal
      hydroxide gel.
AB  - The early stages of the spontaneous hydrolytic polymerization of an active
      hydroxide in the anti-bayerite structure are followed by using molecular dynamics
      simulations. The polymer populations are calculated as a function of reaction
      progress and compared with a model governed by purely random bonding. In
      agreement with experimental observations in aqueous solutions, the transformation
      of singly bridged to doubly bridged metal ions is shown to have a significant
      autocatalytic component. The overall polymer populations, however, are very close
      to the predictions of the random bonding model, indicating that local
      autocatalytic behavior is decoupled from multimer populations at the larger
      scales. The calculations show that solid-state transformation processes do not
      preferentially give rise to higher order multimers, and suggest that interfacial
      processes, involving bulk solution, are required to facilitate rapid
      transformation to higher order oligomers. Two reaction pathways are identified
      for the dewatering of mu-H(3)O(2) bridges into mu-OH bridges. Both are activated
      primarily by undercoordination of one of the metals centers involved in the
      bridge.

PMID- 16599473
TI  - Effect of ozone oxidation on single-walled carbon nanotubes.
AB  - Exposing single-walled carbon nanotubes to room-temperature UV-generated ozone
      leads to an irreversible increase in their electrical resistance. We demonstrate
      that the increased resistance is due to ozone oxidation on the sidewalls of the
      nanotubes rather than at the end caps. Raman and X-ray photoelectron
      spectroscopies show an increase in the defect density due to the oxidation of the
      nanotubes. Using ultraviolet photoelectron spectroscopy, we show that these
      defects represent the removal of pi-conjugated electron states near the Fermi
      level, leading to the observed increase in electrical resistance. Oxidation of
      carbon nanotubes is an important first step in many chemical functionalization
      processes. Because the oxidation rate can be controlled with short exposures, UV
      generated ozone offers the potential for use as a low-thermal-budget processing
      tool.

PMID- 16599474
TI  - Efficient electrocatalyst utilization: electrochemical deposition of Pt
      nanoparticles using nafion membrane as a template.
AB  - We deposit Pt particles electrochemically on an electrode covered with a Nafion
      membrane. Platinum ions travel through the hydrophilic channels of the membrane,
      and platinum deposits are formed at the place where the channels make contact
      with the planar electrode. This procedure deposits the catalyst only at the end
      of the hydrophilic channels that cross the membrane; no catalyst is placed under
      the hydrophobic domains, where it would not be in contact with the electrolyte.
      By performing a series of cyclic voltammograms with this system, we show that
      deposition of the platinum through the membrane achieves better platinum
      utilization than deposition of platinum on the naked electrode followed by the
      placement of the membrane on top.

PMID- 16599475
TI  - Laser-assisted synthesis of superparamagnetic Fe@Au core-shell nanoparticles.
AB  - A novel method combining wet chemistry for synthesis of an Fe core, 532 nm laser
      irradiation of Fe nanoparticles and Au powder in liquid medium for deposition of
      an Au shell, and sequential magnetic extraction/acid washing for purification has
      been developed to fabricate oxidation-resistant Fe@Au magnetic core-shell
      nanoparticles. The nanoparticles have been extensively characterized at various
      stages during and up to several months after completion of the synthesis by a
      suite of electron microscopy techniques (HRTEM, HAADF STEM, EDX), X-ray
      diffraction (XRD), UV-vis spectroscopy, inductively coupled plasma atomic
      emission spectroscopy, and magnetometry. The surface plasmon resonance of the
      Fe@Au nanoparticles is red shifted and much broadened as compared with that of
      pure colloidal nano-gold, which is explained to be predominantly a shell
      thickness effect. The Au shell consists of partially fused approximately 3-nm
      diameter fcc Au nanoparticles (lattice interplanar distance, d = 2.36 A). The 18
      nm-diameter magnetic core is bcc Fe single domain (d = 2.03 A). The nanoparticles
      are superparamagnetic at room temperature (300 K) with a blocking temperature,
      T(b), of approximately 170 K. After 4 months of shelf storage in normal
      laboratory conditions, their mass magnetization per Fe content was measured to be
      210 emu/g, approximately 96% of the Fe bulk value.

PMID- 16599477
TI  - A first-principles investigation of LiNH(2) as a hydrogen-storage material:
      effects of substitutions of K and Mg for Li.
AB  - Li-N-H compounds hold promise as novel hydrogen-storage materials with high
      gravimetric hydrogen densities. Because the dehydriding reaction caused by the
      decomposition of LiNH(2) requires a higher temperature than desired, much effort
      has been devoted to the destabilization of LiNH(2) to decrease the decomposition
      temperature. In particular, there has been recent experimental evidence for
      lowering the temperature by partial substitution of Li by Mg. However, the reason
      is not clear. In this study, we have employed density functional theory to
      investigate LiNH(2) and partially Li-substituted systems aiming to understand the
      effects of the substitution on the destabilization of the NH(2) species. K, a
      more electropositive element, and Mg, a more electronegative element, have been
      chosen as two probes to illustrate the effects. We have focused on the
      investigation of effects of substitutions on the N-H bond strength that is
      regarded as a qualitative indicator of the decomposition temperature. We have
      found that in both cases the N-H bonds are weakened, in particular, the Mg
      substitute appears to be more effective in the destabilization of the NH(2). The
      relative strength of the metal-N ionic bonding has been found to be a key factor
      to explain the effects of the substitutes. These have been discussed in detail in
      terms of Wannier function analyses.

PMID- 16599476
TI  - A TDDFT study of the excited states of DNA bases and their assemblies.
AB  - We present a detailed study of the optical absorption spectra of DNA bases and
      base pairs, carried out by means of time dependent density functional theory. The
      spectra for the isolated bases are compared to available theoretical and
      experimental data and used to assess the accuracy of the method and the quality
      of the exchange-correlation functional. Our approach turns out to be a reliable
      tool to describe the response of the nucleobases. Furthermore, we analyze in
      detail the impact of hydrogen bonding and pi-stacking in the calculated spectra
      for both Watson-Crick base pairs and Watson-Crick stacked assemblies. We show
      that the reduction of the UV absorption intensity (hypochromicity) for light
      polarized along the base-pair plane depends strongly on the type of interaction.
      For light polarized perpendicular to the basal plane, the hypochromicity effect
      is reduced, but another characteristic is found, namely a blue shift of the
      optical spectrum of the base-assembly compared to that of the isolated bases. The
      use of optical tools as fingerprints for the characterization of the structure
      (and type of interaction) is extensively discussed.

PMID- 16599478
TI  - Simulation study of wave propagation instabilities for the combustion synthesis
      of transition metals aluminides.
AB  - Interest in the mode of propagation of self-sustaining reactions has been
      motivated by the influence of the mode on the microstructure and composition of
      the final product. However, comprehensive studies relating the onset of the
      various propagation modes to the chemical and phase transformations taking place
      in the sample are still lacking. In the present work propagation instabilities in
      self-propagating high-temperature synthesis (SHS) of transition metal aluminides
      are studied using a computer simulation approach. The results are presented for
      the SHS of NiAl, CoAl, TiAl, and NbAl(3). Particular emphasis is made with
      respect to the influence of process variables and system parameters on the onset
      of propagation instabilities, in relation to the physicochemical processes taking
      place during the propagation of the combustion front.

PMID- 16599479
TI  - Aggregates of polymer-substituted fullerenes.
AB  - We analyzed the self-organized supermolecular architectures observed in solutions
      of singly polymer-substituted fullerenes by light-scattering and fluorescence
      spectroscopy, as well as the surface pattern obtained from spraying the solution
      by atomic force microscopy. We found that the concentration dependence on
      aggregate size and fluorescence intensity can be explained quantitatively using a
      scaling argument, assuming that the aggregates in solution are self-emulsified
      micelles. Our results indicate that the core of the structure is unreacted
      fullerenes. Based on our scaling arguments, we predict that there is a critical
      molecular weight that allows for a narrow distribution of the self-assembled
      structures in solution.

PMID- 16599480
TI  - NMR study of strontium binding by a micaceous mineral.
AB  - The nature of strontium binding by soil minerals directly affects the transport
      and sequestration/remediation of radioactive strontium species released from
      leaking high-level nuclear waste storage tanks. However, the molecular-level
      structure of strontium binding sites has seldom been explored in phyllosilicate
      minerals by direct spectroscopic means and is not well-understood. In this work,
      we use solid-state NMR to analyze strontium directly and indirectly in a fully
      strontium-exchanged synthetic mica of nominal composition
      Na(4)Mg(6)Al(4)Si(4)O(20)F(4). Thermogravimetric analysis, X-ray diffraction
      analysis, and NMR evidence supports that heat treatment at 500 degrees C for 4 h
      fully dehydrates the mica, creating a hydrogen-free interlayer. Analysis of the
      strontium NMR spectrum of the heat-treated mica shows a single strontium
      environment with a quadrupolar coupling constant of 9.02 MHz and a quadrupolar
      asymmetry parameter of 1.0. These quadrupolar parameters are consistent with a
      highly distorted and asymmetric coordination environment that would be produced
      by strontium cations without water in the coordination sphere bound deep within
      the ditrigonal holes. Evidence for at least one additional strontium environment,
      where proton-strontium couplings may occur, was found via a (1)H-(87)Sr transfer
      of populations by double resonance NMR experiment. We conclude that the strontium
      cations in the proton-free interlayer are observable by (87)Sr NMR and bound
      through electrostatic interactions as nine coordinate inner-sphere complexes
      sitting in the ditrigonal holes. Partially hydrated strontium cations invisible
      to direct (87)Sr NMR are also present and located on the external mica surfaces,
      which are known to hydrate upon exposure to atmospheric moisture. These results
      demonstrate that modern pulsed NMR techniques and high fields can be used
      effectively to provide structural details of strontium binding by phyllosilicate
      minerals.

PMID- 16599481
TI  - Preparing a magnetically responsive single-wall carbon nanohorn colloid by
      anchoring magnetite nanoparticles.
AB  - A single-wall carbon nanohorn (SWNH) colloid was made to be magnetically
      responsive by anchoring magnetite nanoparticles prepared by the homogeneous
      mixing of FeCl(2)-FeCl(3) and NaOH solutions. Transmission electron microscopy
      observation showed the high dispersion of magnetite particles of 2-9 nm on the
      surface of the SWNH colloid, coinciding with the broad X-ray diffraction peaks of
      the magnetites. The magnetization measurements showed that the magnetite
      nanoparticles-anchored SWNH (mag-SWNH) colloid has the hybrid property of
      ferrimagnetism and superparamagnetism. It was demonstrated that mag-SWNH colloid
      dispersed in water by sonication responded to an external magnetic field,
      gathering toward a magnet. N(2) adsorption experiments showed the high
      nanoporosity of mag-SWNHs and that magnetite nanoparticles were preferably
      anchored at "nanowindow" sites and the entrance sites of interstitial pores. This
      magnetically responsive SWNH colloid should contribute to the field of drug
      delivery.

PMID- 16599482
TI  - (7)Li NMR and two-dimensional exchange study of lithium dynamics in monoclinic
      Li(3)V(2)(PO(4))(3).
AB  - High-resolution solid-state (7)Li NMR was used to characterize the structure and
      dynamics of lithium ion transport in monoclinic Li(3)V(2)(PO(4))(3). Under fast
      magic-angle spinning (MAS) conditions (25 kHz), three resonances are clearly
      resolved and assigned to the three unique crystallographic sites. This assignment
      is based on the Fermi-contact delocalization interaction between the unpaired d
      electrons at the vanadium centers and the lithium ions. One-dimensional variable
      temperature NMR and two-dimensional exchange spectroscopy (EXSY) are used to
      probe Li mobility between the three sites. Very fast exchange, on the microsecond
      time scale, was observed for the Li hopping processes. Activation energies are
      determined and correlated to structural properties including interatomic Li
      distances and Li-O bottleneck sizes.

PMID- 16599483
TI  - High rate reversibility anode materials of lithium batteries from vapor-grown
      carbon nanofibers.
AB  - We demonstrate the high-rate capability of lithium ion insertion-deinsertion
      reactions in carbon nanofibers (CNFs). The morphology of CNFs with structural and
      surface defects, due to the mixed features of disordered and graphitic carbon,
      plays an important role in both the enhancement of the lithium ion storage and
      the rate-determining reactions during the topotactic process. The reversible
      specific capacity of the CNFs at a 0.1 C rate was 461 mA x h/g. The most
      promising property, which is expected to overcome the hurdles of lithium
      batteries for high-power applications, is that they deliver considerably high
      specific capacity even at a very high charge-discharge current, i.e., at a
      cycling rate of 10 C the reversible capacity is around 170 mA x h/g with a 95%
      Coulombic efficiency.

PMID- 16599484
TI  - Transferable ordered ni hollow sphere arrays induced by electrodeposition on
      colloidal monolayer.
AB  - We report an electrochemical synthesis of two-dimensionally ordered porous Ni
      arrays based on polystyrene sphere (PS) colloidal monolayer. The morphology can
      be controlled from bowl-like to hollow sphere-like structure by changing
      deposition time under a constant current. Importantly, such ordered Ni arrays on
      a conducting substrate can be transferred integrally to any other desired
      substrates, especially onto an insulting substrate or curved surface. The
      magnetic measurements of the two-dimensional hollow sphere array show the
      coercivity values of 104 Oe for the applied field parallel to the film, and 87 Oe
      for the applied field perpendicular to the film, which is larger than those of
      bulk Ni and hollow Ni submicrometer-sized spheres. The formation of hollow sphere
      arrays is attributed to preferential nucleation on the interstitial sites between
      PS in the colloidal monolayer and substrate, and growth along PSs' surface. The
      transferability of the arrays originates from partial contact between the Ni
      hollow spheres and substrate. Such novel Ni ordered nanostructured arrays with
      transferability and high magnetic properties should be useful in applications
      such as data storage, catalysis, and magnetics.

PMID- 16599485
TI  - Bonding in methylalkalimetals (CH(3)M)(n) (M = Li, Na, K; n = 1, 4). Agreement
      and divergences between AIM and ELF analyses.
AB  - The chemical bonding in methylalkalimetals (CH(3)M)(n)() (M = Li-K; n = 1, 4) has
      been investigated by making use of topological analyses grounded in the theory of
      atoms in molecules (AIM) and in the electron localization function (ELF). Both
      analyses describe the C-M bond as an ionic interaction. However, while AIM
      diagnoses a decrease of ionicity with tetramerization, ELF considers tetramers
      more ionic. Divergences emerge also when dealing with the bonding topology given
      by each technique. For the methylalkalimetal tetramers, the ELF analysis shows
      that each methyl carbon atom interacts through a bond pair with each of the three
      hydrogen atoms belonging to the same methyl group and through an ionic bond with
      the triangular face of the tetrahedral metal cluster in front of which the methyl
      group is located. On the other hand, the AIM topological description escapes from
      the traditional bonding schemes, presenting hypervalent carbon and alkalimetal
      atoms. Our results illustrate that fundamental concepts, such as that of the
      chemical bond, have a different, even colliding meaning in AIM and ELF theories.

PMID- 16599486
TI  - Self-organized hierarchical ZnS/SiO(2) nanowire heterostructures.
AB  - Novel hierarchical heterostructures formed by wrapping ZnS nanowires with highly
      dense SiO(2) nanowires were successfully synthesized by a vapor-liquid-solid
      process. The as-synthesized products were characterized using X-ray diffraction,
      scanning electron microscopy and transmission electron microscopy equipped with
      an energy-dispersive X-ray spectrometer. Studies indicate that a typical
      hierarchical ZnS/SiO(2) heterostructure consists of a single-crystalline ZnS
      nanowire (core) with diameter gradually decreasing from several hundred
      nanometers to 20 nm and adjacent amorphous SiO(2) nanowires (branches) with
      diameters of about 20 nm. A possible growth mechanism was also proposed for the
      growth of the hierarchical heterostructures.

PMID- 16599487
TI  - Molecular dynamics simulations for pure epsilon-CL-20 and epsilon-CL-20-based
      PBXs.
AB  - Molecular dynamics has been employed to simulate the well-known high energy
      density compound epsilon-CL-20 (hexanitrohexaazaisowurtzitane) crystal and 12
      epsilon-CL-20-based PBXs (polymer bonded explosives) with four kinds of typical
      fluorine polymers, i.e., polyvinylidenedifluoride, polychlorotrifluoroethylene,
      fluorine rubber (F(2311)), and fluorine resin (F(2314)) individually. The elastic
      coefficients, isotropic mechanical properties (tensile moduli, bulk moduli, shear
      moduli, and poission's ratios), and bonding energy are first reported for epsilon
      CL-20 crystal and epsilon-CL-20-based polymer bonded explosives (PBXs). The
      mechanical properties of epsilon-CL-20 can be effectively improved by blending
      with a small amount of fluorine polymers, and the whole effect of the adding
      fluorine polymers to improve mechanical properties of PBXs along the three
      crystalline surfaces of epsilon-CL-20 is found to be (100) approximately (001) >
      (010). The interaction between each of the crystalline surfaces and each of the
      fluorine polymers is different, and the ordering of binding energy for the three
      surfaces is (001) > (100) > (010); F(2314) always has the strongest binding
      ability with the three different surfaces. F(2314) can best improve the
      ductibility and tenacity of PBX when it is positioned on epsilon-CL-20 (001)
      crystal surface. The calculations on detonation performances for pure epsilon-CL
      20 crystal and the four epsilon-CL-20-based PBXs show that adding a small amount
      of fluorine polymer into pure epsilon-CL-20 will lower detonation performance,
      but each detonation parameter of the obtained PBXs is still excellent.

PMID- 16599488
TI  - Tuning of copper nanocrystals optical properties with their shapes.
AB  - Copper nanocrystals are obtained by chemical reduction of copper ions in mixed
      reverse micelles. A large excess of reducing agent favors producing a new
      generation of shaped copper nanocrystals as nanodisks, elongated nanocrystals,
      and cubes. By using UV-Visible spectroscopy and numerical optical simulations we
      demonstrate that the optical properties are tuned by the relative proportions of
      spheres and nanodisks.

PMID- 16599489
TI  - Magnetic carbon nanotubes: synthesis by electrostatic self-assembly approach and
      application in biomanipulations.
AB  - Magnetic multiwalled carbon nanotubes (MWNTs) were facilely prepared by the
      electrostatic self-assembly approach. Poly(2-diethylaminoethyl methacrylate)
      (PDEAEMA) was covalently grafted onto the surfaces of MWNTs by MWNT-initiated in
      situ atom transfer radical polymerization (ATRP) of 2-diethylaminoethyl
      methacrylate (DEAEMA). The PDEAEMA-grafted MWNTs were quaternized with methyl
      iodide (CH(3)I), resulting in cationic polyelectrolyte-grafted MWNTs (MWNT-PAmI).
      Magnetic iron oxide (Fe(3)O(4)) nanoparticles were loaded onto the MWNT surfaces
      by electrostatic self-assembling between MWNT-PAmI and Fe(3)O(4), affording
      magnetic nanotubes. The assembled capability of the nanoparticles can be adjusted
      to some extent by changing the feed ratio of Fe(3)O(4) to MWNT-PAmI. The obtained
      magnetic nanotubes were characterized with TEM, EDS, STEM, and element mapping
      analyses. TEM and EDS measurements confirmed the nanostructures and the
      components of the resulting nanoobjects. The magnetic nanotubes were assembled
      onto sheep red blood cells in a phosphate buffer solution, forming magnetic
      cells. The blood cells attached with or without magnetic nanotubes can be
      selectively manipulated in a magnetic field. These results promise a general and
      efficient strategy to magnetic nanotubes and the fascinating potential of such
      magnetic nanoobjects in applications of bionanoscience and technology.

PMID- 16599491
TI  - Tunable one-dimensional silver-silica nanopeapod architectures.
AB  - Silica-coated silver nanowires can be chemically treated to produce a "peapod"
      architecture in which silver peas are embedded in silica pods. The silver "pea"
      dimension and interparticle spacings are controllable down to approximately 50
      nm. This architecture is potentially useful for chemical sensing, plasmonic, or
      catalytic applications.

PMID- 16599490
TI  - Thermochromatism and structural evolution of metastable polydiacetylenic
      crystals.
AB  - Topochemically polymerized sodium 10,12-pentacosadiynoate (PCDA-Na) microcrystals
      show an irreversible red-to-blue chromatic transition accompanied by a distinct
      structural evolution upon initial thermal treatment, and show a subsequent
      completely reversible blue-to-red chromatic transition upon further thermal
      stimuli. Visible absorption spectroscopy, X-ray diffraction (XRD), and
      differential scanning calorimetry (DSC) are used to investigate the
      thermochromatic transition behavior of the polydiacetylenic microcrystals. Brief
      quantum mechanical geometry optimization is employed to explain the lattice
      dimensional change during the irreversible red-to-blue chromatic transition of
      the metastable polydiacetylenic crystals.

PMID- 16599492
TI  - Laser ablation synthesis of gold nanoparticles in organic solvents.
AB  - Free and functionalized gold nanoparticles are synthesized by laser ablation of a
      gold metal plate immersed in dimethyl sulfoxide, acetonitrile, and
      tetrahydrofuran. Functionalized gold nanoparticles are synthesized in a one-step
      process thanks to the solubility of the ligands in these solvents. It is possible
      to have significant control of the concentration, aggregation, and size of the
      particles by varying a few parameters. UV-vis spectroscopy and transmission
      electron microscopy are used for the characterization of the nanoparticles. The
      Mie model for spherical particles and the Gans model for spheroids allow a fast
      and reliable interpretation of experimental UV-vis spectra.

PMID- 16599493
TI  - Calculated absorption and scattering properties of gold nanoparticles of
      different size, shape, and composition: applications in biological imaging and
      biomedicine.
AB  - The selection of nanoparticles for achieving efficient contrast for biological
      and cell imaging applications, as well as for photothermal therapeutic
      applications, is based on the optical properties of the nanoparticles. We use Mie
      theory and discrete dipole approximation method to calculate absorption and
      scattering efficiencies and optical resonance wavelengths for three commonly used
      classes of nanoparticles: gold nanospheres, silica-gold nanoshells, and gold
      nanorods. The calculated spectra clearly reflect the well-known dependence of
      nanoparticle optical properties viz. the resonance wavelength, the extinction
      cross-section, and the ratio of scattering to absorption, on the nanoparticle
      dimensions. A systematic quantitative study of the various trends is presented.
      By increasing the size of gold nanospheres from 20 to 80 nm, the magnitude of
      extinction as well as the relative contribution of scattering to the extinction
      rapidly increases. Gold nanospheres in the size range commonly employed (
      approximately 40 nm) show an absorption cross-section 5 orders higher than
      conventional absorbing dyes, while the magnitude of light scattering by 80-nm
      gold nanospheres is 5 orders higher than the light emission from strongly
      fluorescing dyes. The variation in the plasmon wavelength maximum of nanospheres,
      i.e., from approximately 520 to 550 nm, is however too limited to be useful for
      in vivo applications. Gold nanoshells are found to have optical cross-sections
      comparable to and even higher than the nanospheres. Additionally, their optical
      resonances lie favorably in the near-infrared region. The resonance wavelength
      can be rapidly increased by either increasing the total nanoshell size or
      increasing the ratio of the core-to-shell radius. The total extinction of
      nanoshells shows a linear dependence on their total size, however, it is
      independent of the core/shell radius ratio. The relative scattering contribution
      to the extinction can be rapidly increased by increasing the nanoshell size or
      decreasing the ratio of the core/shell radius. Gold nanorods show optical cross
      sections comparable to nanospheres and nanoshells, however, at much smaller
      effective size. Their optical resonance can be linearly tuned across the near
      infrared region by changing either the effective size or the aspect ratio of the
      nanorods. The total extinction as well as the relative scattering contribution
      increases rapidly with the effective size, however, they are independent of the
      aspect ratio. To compare the effectiveness of nanoparticles of different sizes
      for real biomedical applications, size-normalized optical cross-sections or per
      micron coefficients are calculated. Gold nanorods show per micron absorption and
      scattering coefficients that are an order of magnitude higher than those for
      nanoshells and nanospheres. While nanorods with a higher aspect ratio along with
      a smaller effective radius are the best photoabsorbing nanoparticles, the highest
      scattering contrast for imaging applications is obtained from nanorods of high
      aspect ratio with a larger effective radius.

PMID- 16599494
TI  - Covalent linking of near-infrared luminescent ternary lanthanide (Er(3+), Nd(3+),
      Yb(3+)) complexes on functionalized mesoporous MCM-41 and SBA-15.
AB  - The near-infrared (NIR) luminescent lanthanide ions, such as Er(III), Nd(III),
      and Yb(III), have been paid much attention for the potential use in the optical
      communications or laser systems. For the first time, the NIR-luminescent
      Ln(dbm)(3)phen complexes have been covalently bonded to the ordered mesoporous
      materials MCM-41 and SBA-15 via a functionalized phen group phen-Si (phen-Si = 5
      (N,N-bis-3-(triethoxysilyl)propyl)ureyl-1,10-phenanthroline; dbm =
      dibenzoylmethanate; Ln = Er, Nd, Yb). The synthesis parameters X = 12 and Y = 6 h
      (X denotes Ln(dbm)(3)(H(2)O)(2)/phen-MCM-41 molar ratio or
      Ln(dbm)(3)(H(2)O)(2)/phen-SBA-15 molar ratio and Y is the reaction time for the
      ligand exchange reaction; phen-MCM-41 and phen-SBA-15 are phen-functionalized MCM
      41 and SBA-15 mesoporous materials, respectively) were selected through a
      systematic and comparative study. The derivative materials, denoted as
      Ln(dbm)(3)phen-MCM-41 and Ln(dbm)(3)phen-SBA-15 (Ln = Er, Nd, Yb), were
      characterized by powder X-ray diffraction, nitrogen adsorption/desorption,
      Fourier transform infrared (FT-IR), elemental analysis, and fluorescence spectra.
      Upon excitation of the ligands absorption bands, all these materials show the
      characteristic NIR luminescence of the corresponding lanthanide ions through the
      intramolecular energy transfer from the ligands to the lanthanide ions. The
      excellent NIR-luminescent properties enable these mesoporous materials to have
      potential uses in optical amplifiers (operating at 1.3 or 1.5 mum), laser
      systems, or medical diagnostics. In addition, the Ln(dbm)(3)phen-SBA-15 materials
      show an overall increase in relative luminescent intensity and lifetime compared
      to the Ln(dbm)(3)phen-MCM-41 materials, which was explained by the comparison of
      the lanthanide ion content and the pore structures of the two kinds of mesoporous
      materials in detail.

PMID- 16599495
TI  - Quantum size effect on surface photovoltage spectra: alpha-Fe(2)O(3) nanocrystals
      on the surface of monodispersed silica microsphere.
AB  - A new method for the preparation of Fe(2)O(3) nanoparticle/SiO(2) microsphere
      composites is described, in which fine alpha-Fe(2)O(3) nanocrystals were prepared
      by forced hydrolysis of FeCl(3) aqueous solution. The structure and optical
      spectra of these alpha-Fe(2)O(3) nanocrystals have been studied. Their visible
      optical absorption can be enhanced by their adsorptions on the surface of SiO(2)
      microspheres and thereafter simple packing of these microspheres to the
      aggregated structures. The size-dependent photogenerated surface photovoltage
      spectra (SPS) of these composites were studied, and quantum confinement effects
      of the SPS properties were observed. The transport of photoinduced charges
      between nanocrystals with intrinsic electronic nature of confined states accounts
      for this phenomenon. These results are helpful in understanding the relationship
      among d-d transition and charge-transfer transition in transition metal oxides
      and find applications in photovoltaic devices.

PMID- 16599496
TI  - Intercalation of iron(III) hexacyano complex in a Ni,Al hydrotalcite-like
      compound.
AB  - The product obtained by the intercalation of hexacyanoferrate(III) inside a Ni,
      Al hydrotalcite-like compound (Htlc) has been characterized using XRD, FT-IR,
      Raman, and XAS spectroscopy. The intercalation was carried out by anionic
      exchange of the originally existing chloride ions. The combined use of those
      techniques gave more insight on the insertion chemistry of Htlcs. Extended X-ray
      absorption fine structure spectra of the intercalated Htlc demonstrated that the
      native structure was stable during the iron complex insertion, whereas the
      exchange process occurred with a partial reduction of hexacyanoferrate(III). Both
      Raman and FT-IR spectroscopy pointed out the concomitant formation of
      K(2)NiFe(II)(CN)(6) and KNiFe(III)(CN)(6). The effect of aging on the
      intercalated product is also addressed.

PMID- 16599497
TI  - Influence of bi modification of pt anode catalyst in direct formic acid fuel
      cells.
AB  - The influence of Bi modification of Pt anode catalyst on the performance of
      direct formic acid fuel cells was investigated. Compared with the unmodified Pt
      anode, the Bi modified Pt (PtBi(m)) electrode prepared by under-potential
      deposition (UPD) caused faster electrocatalytic oxidation of formic acid at the
      same value of the overpotential, and thus, PtBi(m) resulted in an increase in the
      power performance of direct formic acid fuel cells. Electrochemical impedance
      spectra helped to explain the difference of performance between the unmodified Pt
      and Bi modified Pt electrodes. Solution conductivity and dehydration phenomena
      occurring in highly concentrated formic acid solutions can also explain the
      higher power performance of PtBi(m).

PMID- 16599498
TI  - Real-time observation of fiber network formation in molecular organogel:
      supersaturation-dependent microstructure and its related rheological property.
AB  - Low-molecular mass organic gelators self-organizing into three-dimensional fiber
      networks within organic solvents have attracted much attention in recent years.
      However, to date, how the microstructure of fiber network is formed in a gelation
      process and the key factors that govern the topological structure of a gel
      network remain to be determined. In this work, we address these issues by
      investigating the in situ formation of the gel networks in the N-lauroyl-l
      glutamic acid di-n-butylamide (GP-1)/propylene glycol (PG) system. By using
      optical microscopy, the time evolution of the gel network microstructure was
      investigated under various supersaturation conditions. It is found that
      supersaturation is one of the key factors that govern the topological structure
      of a gel network. In particular, the creation of the junctions turns out to be
      supersaturation-dependent. The rheological experiments further revealed the
      correlation between topological structure and mechanical properties. It suggests
      that the rheological properties can be effectively modified by tuning the
      microstructure topology of the gel network. Our results reported here provide new
      physical insight into the formation kinetics of a molecular gel. Furthermore,
      this work could be important in constructing and engineering a supramolecular
      structure for the purpose of applications.

PMID- 16599499
TI  - Structural change in Li and Na aluminophosphate glasses: evidence of a
      "structural mixed alkali effect".
AB  - The short- and long-range structure of a series of single and mixed
      aluminophosphate glasses with the general composition [xNa(2)O (46 - x)Li(2)O],
      [yAl(2)O(3) (54 - y)P(2)O(5)] is analyzed using (31)P and (27)Al magic-angle
      spinning (MAS) NMR as well as small-angle X-ray scattering. These series of
      glasses allow analyzing both the effect of alumina incorporation in these
      glasses, for small alumina content (y = 0, 4, 8), and the structural changes
      associated with the so-called mixed alkali effect (x = 0, 11.5, 23, 34.5, 46).
      Our results indicate that aluminum is mainly octahedrally coordinated in these
      glasses and that there is most likely some segregation of the Al(OP)(6) species.
      In the pure phosphate glasses, we observe a "classical" continuous variation of
      the structural properties with the relative alkali content, but in the
      aluminophosphate, both local and long-range structural results reveal for the
      first time some nonlinear change as a function of the relative alkali content.

PMID- 16599500
TI  - Element-specific probe of the magnetic and electronic properties of Dy incar
      fullerenes.
AB  - The magnetic and electronic properties of a single atom and a pair of Dy atoms
      encapsulated inside fullerene carbon cages have been examined using X-ray
      absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD) as
      well as resonant photoelectron spectroscopy (RESPES) across the Dy M(4,5)-edge.
      The comparison of the measured XAS spectra with multiplet calculations indicates
      that the encaged Dy has a 4f( 9) configuration. The presence of Dy 5d spectral
      weight in the valence band is not detected by RESPES, indicating that Dy is in a
      formally trivalent state. The evolution of the encaged Dy orbital and spin
      moments of the 4f orbitals as a function of the applied magnetic field and
      temperature has been obtained from XMCD measurements. At 6.9 T and 4 K, both the
      orbital and the spin magnetic moments of the encaged Dy 4f electrons are
      dramatically smaller than those expected for the free Dy(3+) at saturation.

PMID- 16599501
TI  - Thermal-induced changes in molecular magnets based on prussian blue analogues.
AB  - The thermal-induced changes in molecular magnets based on Prussian blue
      analogues, M(3)[Fe(CN)(6)](2).xH(2)O (M = Mn, Co, Ni, Cu, Zn, and Cd), were
      studied from infrared, X-ray diffraction, thermo-gravimetric, Mossbauer, and
      magnetic data. Upon being heated, these materials loose the crystalline water
      that enhances the interaction between the metal centers, as has been detected
      from Mossbauer spectroscopy data. At higher temperatures, a progressive
      decomposition process takes place, liberating CN(-) groups, which reduces the
      iron atom from Fe(III) to Fe(II) to form hexacyanoferrates(II). The exception
      corresponds to the cobalt compound that undergoes an inner charge transfer to
      form Co(III) hexacyanoferrate(II). In the case of zinc ferricyanide, the thermal
      decomposition is preceded by a structural transformation, from cubic to
      hexagonal. For M = Co, Ni, Cu, and Zn the intermediate reaction product
      corresponds to a solid solution of M(II) ferricyanide and ferrocyanide. For M =
      Mn and Cd the formation of a solid solution on heating was not detected. The
      crystal frameworks of the initial M(II) ferricyanide and of the formed M(II)
      ferrocyanide are quite different. In annealed Mn(II) ferricyanide samples, an
      increasing anti-ferromagnetic contribution on heating, which dominates on the
      initial ferrimagnetic order, was observed. Such a contribution was attributed to
      neighboring Mn(II) ions linked by aquo bridges. In the anhydrous annealed sample
      such interaction disappears. This effect was also studied in pure Mn(II)
      ferrocyanide. The occurrence of linkage isomerism and also the formation of
      Ni(III), Cu(III), and Zn(III) hexacyanoferrates(II) were discarded from the
      obtained experimental evidence.

PMID- 16599502
TI  - Broadband dielectric and resistivity spectroscopy of WO(3) x H(2)O in the range
      of 10(3)-10(10) Hz: particle size effect.
AB  - The interest in studying the electrical properties of WO(3) x H(2)O powders is
      made absolutely necessary because their infrared modulation properties depend on
      their morphologies and electronic populations. Broadband dielectric and
      resistivity spectra of WO(3) x H(2)O powders were recorded in a frequency range
      of 10(3)-10(10) Hz at temperatures varying between 200 and 300 K. Complex
      resistivity and permittivity diagrams have permitted thermal behavior of both dc
      conductivity and permittivity to be obtained. A dielectric relaxation is found,
      attributed to water molecules motions. The role of the powder morphology has been
      investigated on two types of compounds: the first one being constituted by
      nanometric particles and the second by micrometric particles. Strong differences
      are observed in the thermal behaviors of the dc-conductivities (activation
      energies). Particle size effect is evidenced, giving rise to stronger electron
      localization on the nanometric particles. The permittivity values and the
      dynamical behavior of the structural water are also influenced by the particle
      size effect. A strong interaction between moving polarons and water molecules has
      been determined.

PMID- 16599503
TI  - Counteranion dependent protonation and aggregation of tetrakis(4
      sulfonatophenyl)porphyrin in organic solvents.
AB  - The tetrabutylammonium salt of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin
      (TPPS) is soluble in dichloromethane, and the general properties of this compound
      have been investigated as function of various added acids HX (X = Cl, Br, I,
      CF(3)COO, CF(3)SO(3), TFPB) through UV-vis absorption spectroscopy, steady state
      fluorescence emission, and resonance light-scattering (RLS) techniques. Upon
      addition of HX, the initial monomeric free base TPPS is readily converted in an
      aggregated species, whose spectroscopic features are independent of the nature of
      the counteranion X. All the spectroscopic evidence suggest a J-type arrangement
      of chromophores in this aggregate, involving strong hydrogen bonds,
      electrostatic, and dispersive interactions. In the specific case of chloride and
      bromide, in the presence of a TBAX excess, the addition of the corresponding acid
      leads to a monomeric ion-pair between the TBA cations and the diacid TPPS, whose
      central core is strongly interacting with the halide. On further increasing the
      acid concentration in these latter solutions, fully protonated species are formed
      that eventually start to aggregate.

PMID- 16599504
TI  - Preferential destruction of metallic single-walled carbon nanotubes by laser
      irradiation.
AB  - Upon laser irradiation in air, metallic single-walled carbon nanotubes (SWNTs) in
      carbon nanotube thin film can be destroyed in preference to their semiconducting
      counterparts when the wavelength and power intensity of the irradiation are
      appropriate and the carbon nanotubes are not heavily bundled. Our method takes
      advantage of these two species' different rates of photolysis-assisted oxidation,
      creating the possibility of defining the semiconducting portions of carbon
      nanotube (CNT) networks using optical lithography, particularly when constructing
      all-CNT FETs (without metal electrodes) in the future.

PMID- 16599505
TI  - Viscoelastic and structural properties of a phenyl-modified polysiloxane system
      with a three-dimensional structure.
AB  - The relationships between the viscoelastic and structural properties of glass
      forming materials with polysiloxane bonds, which serve as network formers, and
      phenyl groups, which act as network terminators, are examined based on shear
      viscoelasticity, (29)Si MAS NMR, and GPC measurements during the early stages of
      the network-forming process. The viscosities of the present samples do not depend
      on the frequency at temperatures up to 200 degrees C, suggesting that the origin
      of the viscous flow does not include intermolecular entanglement. According to
      the results of the strain dependence of the elastic modulus, the bridging-oxygen
      number, and molecular weight, the present polysiloxane system has a complex
      structure, or distribution of various-sized molecules composed of a polysiloxane
      network with various dimensionalities, and furthermore an elementary process of
      the viscosity is simple flow of these molecules. The structural factors that
      determine the viscosity and its temperature dependence are categorized into the
      molecular size and the intramolecular structure by using a theory based on the
      free-volume model. The relationship between the viscosity and the structure
      around the glass transition temperature is quantitatively examined and it is
      concluded that introducing larger numbers of Ph groups makes the viscosity less
      sensitive to structural factors.

PMID- 16599506
TI  - Influence of the catalyst type on the growth of carbon nanotubes via methane
      chemical vapor deposition.
AB  - The preparation of the catalyst is one of the key parameters which governs the
      quality of carbon nanotubes (CNTs) grown by catalyzed chemical vapor deposition
      (CVD). We investigated the influence of three different procedures of catalyst
      preparation on the type and diameter of CNTs formed under identical growth
      conditions via methane CVD. In the first one, chemically synthesized colloidal
      iron oxide or iron molybdenum alloy nanoparticles were used, which were
      homogeneously deposited on silicon substrates by spin coating to prevent them
      from coalescence under CVD growth conditions. The obtained multiwall CNTs (MWNTs)
      exhibited diameters corresponding to the catalyst particle size, whereas no
      formation of single-wall CNTs (SWNTs) was observed. In the second method,
      commercial porous alumina nanoparticles were used in association with iron and
      molybdenum salts and the Fe/Mo catalyst was formed in situ. We determined that
      the alumina concentration significantly influenced the morphology of the catalyst
      and that below a critical value of the range of 1 g/L no CNTs were formed. While
      yielding nearly defect-free SWNTs, their diameter could not be controlled using
      this procedure, resulting in a large distribution of tube sizes. In a third, new
      preparation method, associating alumina and iron-based nanoparticles, SWNTs of a
      different size and narrower diameter distribution as compared to the second
      method were obtained. Our results are evidence of the essential role of alumina
      particles in the formation of SWNTs, and the newly developed method opens up a
      way to the synthesis of diameter-controlled SWNTs via catalyzed CVD.

PMID- 16599507
TI  - Molecular simulation of excimer fluorescence in polystyrene and
      poly(vinylcarbazole).
AB  - In fluorescence emission spectra of poly(vinylcarbazole) (PVK), two types of
      excimers are observed, the fully and the partially overlapped excimers, namely,
      excimers and exciplexes. In this work, we investigated the structural changes
      induced by the transition between electronic levels S(0) and S(1). Furthermore,
      the widely used assumption of similar potential energy surfaces in the S(0) and
      S(1) states and its use in molecular dynamics simulations are thoroughly examined
      for PVK and polystyrene (PS). The ground-state and excited-state intermolecular
      potentials between phenyl or carbazyl substituents in PS or PVK, respectively,
      are computed from high-level ab initio calculations and fit to analytic
      potentials. Finally, molecular dynamics simulations are performed at room
      temperature for PS and for isotactic and syndiotactic PVK. This treatment enabled
      the decoupling of excimer and exciplex contributions from the simulated spectra.

PMID- 16599508
TI  - Red electrophosphorescence from a soluble binaphthol derivative as host and
      iridium complex as guest.
AB  - The investigation of the optical properties, carrier injection, and transport
      into a soluble small molecule, 6,6'-dicarbazolyl-2,2'-dihexyloxy-1,1'-binaphthol
      (BA), was reported. The results demonstrated that BA is a blue-emitting molecule,
      which can be used as a host for the fabrication of electrophosphorescent light
      emitting diodes (LEDs). The single-layer electrophosphorescent LEDs fabricated
      from toluene solution containing BA with tris[2,5-bis-2'-(9',9'
      dihexylfluorene)pyridine-kappa(2)NC(3)(')]iridium(III) [Ir(HFP)(3)] emitted red
      light from Ir(HFP)(3) triplet emission. The results from photoluminescence (PL)
      and electroluminescence (EL) demonstrated that the dominated operational
      mechanism in EL was charge trapping rather than Forster transfer, which was the
      dominated mechanism in PL. The single-layer OLEDs with 1wt % of Ir(HFP)(3) have a
      luminance (L) of 1000 cd/m(2) at 22 V and a luminous efficiency (LE) of 0.88 cd/A
      at 11 mA/cm(2). Double-layer electrophosphorescent LEDs fabricated by casting the
      emitting layer from a solution of BA blended with Ir(HFP)(3) and subsequently
      thermally depositing tris(8-hydroxyquinoline) aluminum (Alq(3)) film as an
      electron injection and transport layer yielded L = 1830 cd/m(2) at 30 V and LE =
      2.47 cd/A at 18 mA/cm(2). These results demonstrated that electrophosphorescent
      LEDs can be fabricated from BA via solution processing and that L and LE can be
      enhanced by changing the device architecture with the goal of better balancing
      the electron and hole currents.

PMID- 16599509
TI  - Transmission infrared spectroscopy of methyl- and ethyl-terminated silicon(111)
      surfaces.
AB  - Transmission infrared spectroscopy (TIRS) has been used to investigate the
      surface-bound species formed in the two-step chlorination/alkylation reaction of
      crystalline (111)-oriented Si surfaces. Spectra were obtained after hydrogen
      termination, chlorine termination, and reaction of the Cl-Si(111) surface with
      CH(3)MgX or C(2)H(5)MgX (X = Cl, Br) to form methyl (CH(3))- or ethyl (C(2)H(5))
      terminated Si(111) surfaces, respectively. Freshly etched H-terminated Si(111)
      surfaces that were subsequently chlorinated by immersion in a saturated solution
      of PCl(5) in chlorobenzene were characterized by complete loss of the Si-H
      stretching and bending modes at 2083 and 627 cm(-1)(,) respectively, and the
      appearance of Si-Cl modes at 583 and 528 cm(-1). TIRS of the CH(3)-terminated
      Si(111) surface exhibited a peak at 1257 cm(-1) polarized perpendicular to the
      surface assigned to the C-H symmetrical bending, or "umbrella" motion, of the
      methyl group. A peak observed at 757 cm(-1) polarized parallel to the surface was
      assigned to the C-H rocking motion. Alkyl C-H stretch modes on both the CH(3)-
      and C(2)H(5)-terminated surfaces were observed near 2900 cm(-1). The C(2)H(5)
      terminated Si(111) surface additionally exhibited broad bands at 2068 and 2080
      cm(-1), respectively, polarized perpendicular to the surface, as well as peaks at
      620 and 627 cm(-1), respectively, polarized parallel to the surface. These modes
      were assigned to the Si-H stretching and bending motions, respectively, resulting
      from H-termination of surface atoms that did not form Si-C bonds during the
      ethylation reaction.

PMID- 16599510
TI  - Adsorption of unsaturated hydrocarbon moieties on H:Si(111) by Grignard reaction.
AB  - Grafting of unsaturated hydrocarbon moieties (-CH(2)-CH=CH(2), -CH=CH(2), -CH(2)
      CH=CH-CH(3), and -CCH) by a C-Si covalent bond was attempted by the Grignard
      reaction on hydrogen-terminated Si(111) in tetrahydrofuran solutions. The product
      adsorbates were monitored by vibrational methods of high-resolution electron
      energy loss spectroscopy and multiple internal infrared reflection absorption
      spectroscopy, as well as Auger electron spectroscopy. The temperature and the
      period of reaction were adjusted so as to preserve the unsaturated carbon-carbon
      bonds. The -CH(2)-CH=CH(2) group was introduced by a mild reaction condition,
      with the reservation of the C=C double bond confirmed. The unsaturated bonds in 
      CH(2)-CH=CH-CH(3) and -CCH were also reserved. Only in the case of -CH=CH(2) was
      the reservation of the C=C double bond not realized. Unsaturated hydrocarbon
      moieties are applicable for further organic modification to introduce functional
      groups, and are prospective materials in nanofabrication and biological
      application on silicon wafer surfaces.

PMID- 16599511
TI  - Movement of proteins in an environment crowded by surfactant micelles: anomalous
      versus normal diffusion.
AB  - Small proteins move in crowded cell compartments by anomalous diffusion. In many
      of them, e.g., the endoplasmic reticulum, the proteins move between lipid
      membranes in the aqueous lumen. Molecular crowding in vitro offers a systematic
      way to study anomalous and normal diffusion in a well controlled environment not
      accessible in vivo. We prepared a crowded environment in vitro consisting of
      hexaethylene glycol monododecyl ether (C(12)E(6)) nonionic surfactant and water
      and observed lysozyme diffusion between elongated micelles. We have fitted the
      data obtained in fluorescence correlation spectroscopy using an anomalous
      diffusion model and a two-component normal diffusion model. For a small
      concentration of surfactant (below 4 wt %) the data can be fitted by single
      component normal diffusion. For larger concentrations the normal diffusion fit
      gave two components: one very slow and one fast. The amplitude of the slow
      component grows with C(12)E(6) concentration. The ratio of diffusion coefficients
      (slow to fast) is on the order of 0.1 for all concentrations of surfactant in the
      solution. The fast diffusion is due to free proteins while the slow one is due to
      the protein-micelle complexes. The protein-micelle interaction is weak since even
      in a highly concentrated solution (35% of C(12)E(6)) the amplitude of the slow
      mode is only 10%, despite the fact that the average distance between the micelles
      is the same as the size of the protein. The anomalous diffusion model gave the
      anomaly index (r(2)(t) approximately t(alpha)), alpha monotonically decreasing
      from alpha = 1 (at 4% surfactant) to alpha = 0.88 (at 37% surfactant). The fits
      for two-component normal diffusion and anomalous diffusion were of equally good
      quality, but the physical interpretation was only straightforward for the former.

PMID- 16599512
TI  - Electrochemical reversibility of vinylferrocene monolayers covalently attached on
      H-terminated p-Si(100).
AB  - A reversible electrochemical behavior is demonstrated on a specially prepared
      redox-functionalized H-Si(100) surface, obtained via an extra-mild grafting
      procedure from vinylferrocene. The results of a detailed XPS and electrochemical
      characterization of the resulting hybrid are reported and discussed to propose it
      as a reference system for high-quality electroactive monolayers on Si. The
      investigated ferrocene derivative bears a functional group suitable for a mild
      route to covalent anchoring on Si, which is based on a photoinduced reaction with
      visible light under an inert atmosphere. Electrochemical reversibility is shown
      by sharp symmetric voltammograms on freshly prepared p-Si electrodes. Anodic
      oxide growth is responsible for the progressive degradation of the
      electrochemical response. Still, fast electron transfer to the surface redox
      species is maintained during several thousands cycles.

PMID- 16599513
TI  - Dynamics and spectroscopy of hydrogen atoms on Pd{111}.
AB  - Chemisorption of hydrogen on Pd{111} is a relatively simple, yet important
      surface chemical process. By using low-temperature scanning tunneling microscopy,
      tip-induced motion of adsorbed atomic hydrogen at 4 K has been observed at low
      coverage. The motion has been ascribed to excitation of vibrational modes that
      decay into translational modes; vibrational spectroscopy via inelastic electron
      tunneling corroborates this assignment, and the barrier to hydrogen atom motion
      has been determined. At higher coverages, tip-induced motion of vacancies in the
      hydrogen overlayer is observed, and the associated barrier has also been
      determined.

PMID- 16599514
TI  - Probing microstructure evolution during the hardening of gypsum by proton NMR
      relaxometry.
AB  - We report a comprehensive proton NMR relaxation study of the water confined in
      the evolving porous structure of hardened gypsum prepared with different water-to
      plaster ratios (w/p) and increasing additions of crushed gypsum. This study gives
      some new information on the microstructure, the water distribution, and the
      hydration kinetics without any drying or perturbing preparation. The bi
      exponential transverse magnetization decay reveals the existence of two water
      populations in slow exchange. However, the different behaviors of these
      populations during saturation and desaturation experiments show evidence of a
      fast exchange of each population with the surface. Two modes of organization of
      the microstructure of this material are identified through an original model of
      exchange as a function of the water-to-plaster ratio (0.4 < or = w/p < or = 0.6
      and 0.7 < or = w/p < or = 1). A clear gap is shown in the exchange rate value
      above w/p = 0.6 that could be representative of a percolation threshold. Both the
      method and the theory presented can be applied more widely to other porous media
      with reactive surface areas.

PMID- 16599515
TI  - Simulating temperature programmed desorption of water on hydrated gamma-alumina
      from first-principles calculations.
AB  - The knowledge of the properties of gamma-alumina is of great importance in order
      to control its surface for numerous applications. We investigate the kinetic
      behavior of the hydrated alumina (110) surface toward water desorption: the
      minimum energy path is presented for successive desorption steps starting from
      the completely hydrated surface toward the dehydrated one. It appears that water
      desorption is a non activated process. A kinetic model is proposed based on an
      extension of the Eyring theory. This model is a useful tool to understand the
      evolution of water coverage during the pretreatment of alumina. It is then used
      to model temperature programmed desorption experiments for various heating rates.
      The shape of the desorption curve is qualitatively reproduced, and the
      differences between theory and experiments are discussed.

PMID- 16599516
TI  - Orientation effects on nitric acid dihydrate films.
AB  - An investigation of orientation effects in films of nitric acid dihydrate (NAD)
      is presented, based on a systematic study of transmission and reflection
      absorption infrared (RAIR) spectra of samples of varying thickness. The samples
      are prepared by vapor deposition on Ge (for transmission spectroscopy) and on Al
      substrates (for RAIR spectroscopy) at 175 K to produce crystalline alpha-NAD
      films. Transmission spectra were recorded at normal incidence, and RAIR spectra
      were recorded at a grazing angle of 75 degrees, with polarized radiation. The
      observed spectra are compared with predictions of a classical Fresnel model, to
      test the available optical indices of NAD, which are of great importance for the
      accurate interpretation of data from remote sensing measurements. Whereas the
      procedure yields satisfactory results for transmission and s-polarized RAIR
      spectra, it is found that the agreement is not acceptable for p-polarized RAIR
      spectra. An explanation is suggested in terms of a preferential alignment of the
      films, with the (10-1) crystallographic plane of the crystal situated parallel to
      the substrate. The infrared activity of a band at approximately 1170 cm(-1) is
      explained in terms of a preferential orientation of the crystal domains in the
      film.

PMID- 16599517
TI  - Studies of Langmuir-Blodgett films of an ion pair metal complex containing
      Eu(III)-Ru(II) dual chromophores.
AB  - A surfactant ion-pair complex, [Ru(bpy)(2)L][Eu(NTA)(4)](2) (in which L = 1
      docosyl-2-(2- pyridyl)benzimidazole, bpy = 2,2'-bipyridine, and NTA = 4,4,4
      trifluoro-1-(2-naphthyl)-1,3-butanedionato) has been synthesized. The surface
      pressure-area isotherm measurements show that the complex forms a stable Langmuir
      film at the air-water interface without adding any electrolytes into the
      subphase. The monolayers formed at the surface pressures of 5 mN m(-1) and 20 mN
      m(-1), have been successfully transferred onto glass and quartz substrates with
      the transfer ratios close to unity. The Langmuir-Blodgett films were studied by
      UV-visible, infrared, and emission spectroscopies, atomic force microscopy, and
      cyclic voltammetry. The optical, redox, and morphology properties of the LB films
      were found to be significantly affected by the target surface pressures used for
      the film depositions.

PMID- 16599518
TI  - Application of a "black body" like reactor for measurements of quantum yields of
      photochemical reactions in heterogeneous systems.
AB  - We report for the first time an experimental application of the concept of a
      "black body" like reactor to measure quantum yields (Phi) of photochemical
      reactions in liquid-solid heterogeneous systems. A major advantage of this new
      method is its simplicity since the fractions of reflected and transmitted light
      are negligible due to reactor geometry and high optical density of the
      heterogeneous systems. The average quantum yield of a test reaction (phenol
      photodegradation) over TiO(2) (Degussa P25) as determined by this method was
      0.14, identical to the quantum yield measured earlier for this same reaction
      under similar conditions by Salinaro and Serpone. We also report the quantum
      yield of phenol photodegradation over N-doped TiO(2) during photoexcitation at
      the fundamental absorption band (lambda = 365 nm; Phi = 0.12) and at the N-doping
      induced extrinsic absorption band (lambda = 436 nm; Phi = 0.08) of the
      photocatalyst.

PMID- 16599519
TI  - Molecular modeling of phosphonate molecules onto barium sulfate terraced
      surfaces.
AB  - The adsorption of phosphonate molecules onto mineral surfaces is of interest due
      to their use as scale inhibitors. Molecular modeling is an important tool that
      can aid the fundamental understanding of how these inhibitors operate. This paper
      presents an empirical molecular mechanics study of the adsorption of a series of
      straight chain phosphonate molecules onto barium sulfate. It has been found that
      inhibition can be predicted for this straight chain series of molecules, which
      differ by the number of phosphonate groups present as well as by the chain
      length. Even more importantly, the modeling results can predict which faces will
      be preferred, and this has been verified by scanning and transmission electron
      microscopy on the resultant barite particles. It has been found that, in general,
      lattice matching results in the lowest replacement energy for all of the organic
      molecules investigated. The agreement between the experiment and the model
      confirms that the dominant mechanism of interaction for the additives on barium
      sulfate is via the deprotonated phosphonate groups with the barium ions on the
      surface.

PMID- 16599520
TI  - Polysulfone-ZrO(2) surface interactions. The influence on formation, morphology
      and properties of zirfon-membranes.
AB  - The interaction between polysulfone and ZrO(2) particles is studied as a function
      of the particle sintering temperature in order to understand the role of ZrO(2)
      on the formation, morphology, and properties of organo-mineral composite
      membranes. The adsorption between the sintered ZrO(2) and the constituents of
      polysulfone, 2,2-diphenylpropane and diphenyl sulfone, is investigated using high
      pressure liquid chromatography. The influence of the polymer-ZrO(2) interaction
      on the flow behavior of the casting suspension is registered via viscoelastic
      measurements. The organo-mineral composite membranes are formed by immersion
      precipitation in water, and the resulting membrane morphology is analyzed using
      high-resolution SEM. The zirconia concentration in the top-layer of the composite
      structure is determined by XPS. Finally, the link between the polymer-filler
      interactions, the membrane formation process, and the resulting membrane
      structure and properties is established.

PMID- 16599521
TI  - Control of a surface photochemical process by fractal electron transport across
      the surface: O(2) photodesorption from TiO(2)(110).
AB  - The photodesorption of O(2) from TiO(2)(110) has been found to exhibit fractal
      kinetic behavior. The rate coefficient for photodesorption is measured throughout
      the entire experiment and is shown to decrease by a factor of approximately 100
      over a time period of approximately 250 s. A model is proposed in which the
      electrons associated with O-vacancy defects on the surface percolate from vacancy
      site to vacancy site via the filled orbitals at these sites to neutralize
      photoproduced holes. This electron percolation, causing electron-hole
      recombination, reduces the efficiency of charge transfer between a photoproduced
      hole and an O(2)(-)(a) species localized at a vacancy defect site, causing the
      rate of O(2) photodesorption to follow a fractal rate law. We postulate that the
      fractal electron conduction path across the surface is one-dimensional.

PMID- 16599522
TI  - Global optimization study of small (10 < or = N < or = 120) Pd clusters supported
      on MgO(100).
AB  - Experimental evidence suggests that Pd clusters on MgO, known to be good reaction
      catalysts, have face centered cubic (fcc) epitaxial structures. The structure of
      such clusters is the result of the interplay of Pd-Pd and Pd-substrate bonds, the
      former inclined to favor icosahedral (Ih) and decahedral (Dh)-like structures,
      the latter leading to place Pd atoms on top of oxygen sites, according to an
      epitaxial stacking. This paper shows the results of a basin-hopping global
      optimization procedure applied to free and MgO-supported Pd clusters in the size
      range 10 < or = N < or = 120. Pd-MgO interactions are modeled by an analytical
      function fitted to ab initio results, while Pd-Pd interactions are modeled by a
      semiempirical potential. Besides the tight-binding Rosato-Guillope-Legrand (RGL)
      potential, we have adopted a modified version of RGL that better reproduces the
      experimental surface energy of palladium, modifying the attractive part of Pd
      atoms potential energy. We have compared the two potential models, and as a
      result, the RGL potential favors clusters with epitaxial arrangements, so that
      cluster structures are epitaxial fcc in almost all the size ranges considered. On
      the contrary, the alternative potential model preserves some Ih-like
      characteristics typical of the free Pd clusters, and it suggests that a
      transition size from Ih-like to epitaxial structures can take place at about 100
      atoms.

PMID- 16599523
TI  - The dependence of the electronic conductivity of carbon molecular sieve
      electrodes on their charging states.
AB  - The dependence of the electronic conductivity of activated carbon electrodes on
      their potential in electrolyte solutions was examined. Kapton polymer films
      underwent carbonization (1000 degrees C), followed by a mild oxidation process
      (CO(2) at 900 degrees C) for various periods of time, to obtain carbons of
      different pore structures. A specially designed cell was assembled in order to
      measure the conductivity of carbon electrodes at different potentials in
      solutions. When the carbon electrodes possessed molecular sieving properties, a
      remarkable dependence of their conductivity on their charging state was observed.
      Aqueous electrolyte solutions containing ions of different sizes were used in
      order to demonstrate this phenomenon. As the average pore size of the activated
      carbons was larger, their molecular sieving ability was lower, and the dependence
      of their conductivity on their charging state regained its classical form. This
      behavior is discussed herein.

PMID- 16599524
TI  - Gas-phase interaction of thiophene with the Ti(8)C(12)(+) and Ti(8)C(12) met-car
      clusters.
AB  - The reactivity of the Ti(8)C(12)(+) met-car cation toward thiophene was
      investigated using density functional theory (DFT) and mass selective ion
      chemistry. It is shown that the experimentally observed mass spectrum can be well
      described by the DFT calculations. In contrast to the weak bonding interactions
      seen for thiophene on a TiC(001) surface, the Ti(8)C(12)(+) met-car cation is
      able to interact strongly with up to four thiophene molecules with the cluster
      staying intact. In the most stable conformation, the thiophene molecules bond to
      the four low-coordinated Ti(0) sites of Ti(8)C(12)(+) via a eta(5)-C,S
      coordination. The stability and the activity of the Ti(8)C(12)(+) met-car is
      observed to increase with an increasing number of attached thiophene molecules at
      the Ti(0) sites, which is associated with a significant transfer of electron
      density from thiophene to the cluster. The additional electron density on the
      Ti(8)C(12)(+) cation cluster, however, is not sufficient to cleave the C-S bonds
      of thiophene and the dissociation reaction of thiophene is predicted to be a
      highly activated process. By contrast, DFT calculations for the neutral
      Ti(8)C(12) met-car predict that the dissociation reaction leading to adsorbed S
      and C(4)H(4) fragments is energetically favorable for the first thiophene
      molecule. The binding behavior for subsequent addition of thiophene molecules to
      the neutral met-car is also presented and compared to that of the cation.

PMID- 16599525
TI  - Modulation of molecular conductance induced by electrode atomic species and
      interface geometry.
AB  - We present a systematic theoretical investigation of the interaction of an
      organic molecule with gold and palladium electrodes. We show that the chemical
      nature of the electrode elicits significant geometrical changes in the molecule.
      These changes, which are characteristic of the electrode atomic species and the
      interface geometry, are shown to occur at distances as great as 10 Angstrom from
      the interface, leading to a significant modification of the inherent electronic
      properties of the molecule. In certain interface geometries, the highest occupied
      molecular orbital (HOMO) of the palladium-contacted molecule exhibits enhanced
      charge delocalization at the center of the molecule, compared to gold. Also, the
      energy gap between the conductance peak of the lowest unoccupied molecular
      orbital (LUMO) and the Fermi level is smaller for the case of the palladium
      electrode, thereby giving rise to a higher current level at a given bias than the
      gold-contacted molecule. These results indicate that an optimal choice of the
      atomic species and contact geometry could lead to significantly enhanced
      conductance of molecular devices and could serve as a viable alternative to
      molecular derivatization.

PMID- 16599526
TI  - Interaction of Pt clusters with the anatase TiO(2)(101) surface: a first
      principles study.
AB  - The adsorption of Pt(n)() (n = 1-3) clusters on the defect-free anatase
      TiO(2)(101) surface has been studied using total energy pseudopotential
      calculations based on density functional theory. The defect-free anatase
      TiO(2)(101) surface has a stepped structure with a step width of two O-Ti bond
      distances in the (100) plane along the [10] direction and the edge of the step is
      formed by 2-fold-coordinated oxygen atoms along the [010] direction. For a single
      Pt adatom, three adsorption sites were found to be stable. Energetically, the Pt
      adatom prefers the bridge site formed by 2 2-fold-coordinated oxygen atoms with
      an adsorption energy of 2.84 eV. Electronic structure analysis showed that the Pt
      O bonds formed upon Pt adsorption are covalent. Among six stable Pt(2) adsorption
      configurations examined, Pt(2) was found to energetically favor the O-O bridge
      sites on the step edge along [010] with the Pt-Pt bond axis perpendicular to
      [010]. In these configurations, one of the Pt atoms occupies the same O-O bridge
      site as for a single Pt adatom and the other one either binds a different 2-fold
      coordinated oxygen atom on the upper step or a 5-fold-coordinated Ti atom on the
      lower terrace. Three triangular and three open Pt(3) structures were determined
      as minima for Pt(3) adsorption on the surface. Platinum trimers adsorbed in
      triangular structures are more stable than in open structures. In the most stable
      configuration, Pt(3) occupies the edge O-O site with the Pt(3) plane being
      upright and almost perpendicular to the [001] terrace. The preference of Pt(n)()
      to the coordinately unsaturated 2-fold-coordinated oxygen sites indicates that
      these sites may serve as nucleation centers for the growth of metal clusters on
      the oxide surface. The increase in clustering energy with increasing size of the
      adsorbed Pt clusters indicates that the growth of Pt on this surface will lead to
      the formation of three-dimensional particles.

PMID- 16599527
TI  - Density functional theory for planar electric double layers: closing the gap
      between simple and polyelectrolytes.
AB  - We report a nonlocal density functional theory (NLDFT) for polyelectrolyte
      solutions within the primitive model; i.e., the solvent is represented by a
      continuous dielectric medium, and the small ions and polyions by single and
      tangentially connected charged hard spheres, respectively. The excess Helmholtz
      energy functional is derived from a modified fundamental measure theory for hard
      sphere repulsion, an extended first-order thermodynamic perturbation theory for
      chain connectivity, and a quadratic functional Taylor expansion for electrostatic
      correlations. With the direct and cavity correlation functions of the
      corresponding monomeric systems as inputs, the NLDFT predicts the segment-level
      microscopic structures and adsorption isotherms of polyelectrolytes at oppositely
      charged surfaces in good agreement with molecular simulations. In particular, it
      faithfully reproduces the layering structures of polyions, charge inversion, and
      overcharging that cannot be captured by alternative methods including the
      polyelectrolyte Poisson-Boltzmann equation and an earlier version of DFT. The
      NLDFT has also been used to investigate the influences of the small ion valence,
      polyion chain length, and size disparity between polyion segments and counterions
      on the microscopic structure, mean electrostatic potential, and overcharging in
      planar electric double layers containing polyelectrolytes.

PMID- 16599528
TI  - Using spectroscopic data on imidazolium cation conformations to test a molecular
      force field for ionic liquids.
AB  - A molecular force field for the computer simulation of ionic liquids is evaluated
      a posteriori by confrontation against Raman spectroscopic data, published after
      the force field had been formulated. Specifically, the terms in the force field
      describing the conformational aspects of dialkylimidazolium cations, which were
      specifically developed for these compounds using high level ab initio
      calculations, are those affecting the distribution of conformers in simulated
      ionic liquids. Those distributions are compared with analyses of the liquid-phase
      Raman spectra, and the features of a series of dihedral torsions along the alkyl
      side chains in 1-alkyl-3-methylimidazolium cations in several ionic liquids are
      discussed.

PMID- 16599529
TI  - Molecular dynamics study of polarizable ion models for molten AgBr.
AB  - Three different polarizable ion models for molten AgBr have been studied by
      molecular dynamics simulations. The three models are based on a rigid ion model
      (RIM) with a pair potential of the type proposed by Vashishta and Rahman for
      alpha-AgI, to which the induced dipole polarization of the ions is added. In the
      first (PIM1) the dipole moments are only induced by the local electric field,
      while in the other two (PIM1s and PIM2s) a short-range overlap induced
      polarization opposes the electrically induced dipole moments. In the PIM1 and the
      PIM1s only the anions are assumed polarizable, while in the PIM2s both species
      are polarizable. Long molecular dynamics simulations show that the PIM2s is an
      unphysical model since, for some improbable but possible critical configurations,
      the ions become infinitely polarized. The results of using the PIM1, the PIM1s,
      as well as those of the simple RIM, have been compared for the static structure
      and ionic transport properties. The PIM1 reproduces the broad main peak of the
      total structure factor present in the neutron diffraction data, although the
      smoothed three-peak feature of this broad peak is slightly overestimated. The
      structural results for the PIM1s are intermediate between those for the RIM and
      the PIM1, but fail to reproduce the experimental features within the broad
      principal peak. Concerning the ionic transport properties, the value of the
      conductivity obtained using PIM1 is in good agreement with experimental values,
      while the self-diffusion coefficients and the conductivity for the PIM1s are
      lower than the corresponding values using the PIM1 and the RIM.

PMID- 16599530
TI  - Monte carlo computer simulation of chain formation from nanoparticles.
AB  - Spontaneous assembly of long chains of nanoparticles (NPs) has been
      experimentally observed for many different materials including nanocolloids of
      semiconductors, metal oxides, and metals. While the origin of dipole moment in
      various colloids can be different, a universal explanation of chain assembly can
      be provided by the hypothesis of dipole-dipole attraction of nanocolloids. In
      this paper, we describe the application of the Monte Carlo method for modeling of
      self-organization of large ensembles of NPs. As the first approximation, the
      Derjaguin-Landau-Verwey-Overbeek (DLVO) theory provides an adequate description
      of self-organization of several hundreds of NPs. Unlike microscale colloids that
      served as a classical model for DLVO, we used a distance-dependent media
      dielectric constant. The simulated chains are morphologically and geometrically
      similar to those observed experimentally. This establishes the fundamentally
      important ability of NPs to self-assemble due to their intrinsic anisotropy.
      Thermodynamic analysis of Monte Carlo results reveals the role of partial removal
      of the stabilizer shell in CdTe nanocolloids necessary for reduction of
      interparticle repulsion. Analysis of the field distribution around short chains
      demonstrates that the growth of linear agglomerates is kinetically controlled by
      a high activation barrier for NPs approaching from all of the directions except
      one end of the chain. The presented algorithm can be applied to other
      interparticle interactions, such as induced dipoles, which can stimulate chain
      formation in the absence of permanent dipole moment. It can also serve as a
      theoretical foundation for the understanding of the large complex superstructures
      forming from anisotropic and anisometric NPs. Monte Carlo simulation of nanoscale
      dipoles can also be extended to the interactions of NP with proteins, and related
      biological systems important for a variety of applications in medicine.

PMID- 16599531
TI  - Chemical turbulence and line defects induced by gradient effects in a three
      dimensional reaction-diffusion system.
AB  - We report experimental observations of chemical turbulence and line defects in a
      three-dimensional (3-D) Belousov-Zhabotinsky (BZ) reaction-diffusion system.
      Transitions from spiral waves to 3-D chemical turbulence to line defects are
      observed. These transitions are caused by concentration gradients across the
      third dimension in the 3-D reaction medium, indicating the observed line defects
      have a 3-D structure. The line defects come out of the 3-D turbulent state, and
      become smooth with the increase of the control parameter. Simulation with the two
      variable Oregonator model in the 3-D system reproduces similar line defects.

PMID- 16599532
TI  - Molecular dynamics simulation study of superhydrated perdeuterated natrolite
      using a new interaction potential model.
AB  - To test a new interaction potential, molecular dynamics simulations of zeolite
      natrolite were performed for the structures under ambient conditions hydrated by
      perdeuterated water and at high pressure (1.87 GPa) in the superhydrated phase,
      which were recently studied by neutron diffraction. The experimental structures
      were reproduced with reasonable accuracy, and the hydrogen bond features are
      discussed. As in ordinary natrolite, a flip motion of water molecules around the
      HOH bisector is found, which, together with translational oscillations, gives
      rise to transient hydrogen bonds between water molecules, which do not appear
      from experimental equilibrium coordinates. The dynamics of water molecules can
      explain some problems encountered in refining the experimental structure.
      Vibrational spectra of natrolite containing perdeuterated water, which are not
      yet measured, were simulated, and their qualitative trend is discussed.

PMID- 16599533
TI  - The role of excited Rydberg States in electron transfer dissociation.
AB  - Ab initio electronic structure methods are used to estimate the cross sections
      for electron transfer from donor anions having electron binding energies ranging
      from 0.001 to 0.6 eV to each of three sites in a model disulfide-linked molecular
      cation. The three sites are (1) the S-S sigma(*) orbital to which electron
      attachment is rendered exothermic by Coulomb stabilization from the nearby
      positive site, (2) the ground Rydberg orbital of the -NH(3)(+) site, and (3)
      excited Rydberg orbitals of the same -NH(3)(+) site. It is found that attachment
      to the ground Rydberg orbital has a somewhat higher cross section than attachment
      to either the sigma orbital or the excited Rydberg orbital. However, it is
      through attachment either to the sigma(*) orbital or to certain excited Rydberg
      orbitals that cleavage of the S-S bond is most likely to occur. Attachment to the
      sigma(*) orbital causes prompt cleavage because the sigma energy surface is
      repulsive (except at very long range). Attachment to the ground or excited
      Rydberg state causes the S-S bond to rupture only once a through-bond electron
      transfer from the Rydberg orbital to the S-S sigma(*) orbital takes place. For
      the ground Rydberg state, this transfer requires surmounting an approximately 0.4
      eV barrier that renders the S-S bond cleavage rate slow. However, for the excited
      Rydberg state, the intramolecular electron transfer has a much smaller barrier
      and is prompt.

PMID- 16599534
TI  - Gaseous bradykinin and its singly, doubly, and triply protonated forms: a first
      principles study.
AB  - The conformers of gaseous bradykinin, BK, (Arg(1)-Pro(2)-Pro(3)-Gly(4)-Phe(5)
      Ser(6)-Pro(7)-Phe(8)-Arg(9)) and its protonated forms, [BK + H](+), [BK +
      2H](2+), and [BK + 3H](3+), were examined theoretically using a combination of
      the Merck molecular force field, Hartree-Fock, and density functional theory.
      Neutral BK, [BK + H](+), and [BK + 2H](2+) exist in zwitterionic forms that are
      stabilized by internal solvation and have compact structures; [BK + 3H](3+)
      differs by the absence of a salt bridge and adopts an elongated form. The common
      structural feature in all four BK species is a beta-turn in the Ser(6)-Pro(7)
      Phe(8)-Arg(9) sequence. The gas-phase basicity of [BK + H](+) estimated from the
      calculated protonation energy is in accord with published experimental basicity;
      population-weighted collision cross-sections of the three ionic forms are in
      agreement with experimental cross-sections in the literature.

PMID- 16599535
TI  - On the effect of a point mutation on the reactivity of CuZn superoxide dismutase:
      a theoretical study.
AB  - In this paper, we investigate the effects of a point mutation on the enzymatic
      activity of copper-zinc superoxide dismutase, which we recently studied in detail
      by means of a theoretical-computational procedure. Comparison of the reactivity
      of the initial catalytic steps in this mutant (G93A mutation far from the active
      site) with our previous data, reveals the beautiful mechanical-dynamical
      architecture of the enzyme, altered by such an apparently irrelevant mutation.
      Finally, our results suggest a possible atomic-molecular-based explanation for
      the mutant-pathology correlation, in line with the most recent experimental data.

PMID- 16599537
TI  - A triplet mechanism for the formation of cyclobutane pyrimidine dimers in UV
      irradiated DNA.
AB  - The reaction pathways for the photochemical formation of cyclobutane thymine
      dimers in DNA are explored using hybrid density functional theory techniques. It
      is concluded that the thymine-thymine [2 + 2] cycloaddition displays favorable
      energy barriers and reaction energies in both the triplet and the singlet excited
      states. The stepwise cycloaddition in the triplet excited state involves the
      initial formation of a diradical followed by ring closure via singlet-triplet
      interaction. The triplet mechanism is thus completely different from the
      concerted singlet state cycloaddition processes. The key geometric features and
      electron spin densities are also discussed. Bulk solvation has a major effect by
      reducing the barriers and increasing the diradical stabilities. The present
      results provide a rationale for the faster cycloreaction observed in the singlet
      excited states than in the triplet excited states.

PMID- 16599536
TI  - Local structure of beta-hairpin isotopomers by FTIR, 2D IR, and ab initio theory.
AB  - The 12-residue tryptophan zipper beta-hairpin (SWTWENGKWTWK) and two (13)C
      isotopomers were examined in the amide-I region using FTIR and femtosecond two
      dimensional infrared (2D IR) spectroscopies. Spectroscopic features of the
      labeled transitions with (13)C-substituted amide unit present in the terminal or
      turn region of the hairpin, including their frequency shifts and distributions,
      line broadenings, orientations, and anharmonicities of diagonal peaks, allow the
      peptide local structure and local environment to be examined. The results suggest
      a larger structure fluctuation in the terminal region than in the turn region as
      a result of the side chain effect and solvent-peptide interaction. The results
      also suggest that the uncoupled amide-I modes are not degenerate and that this is
      likely to be a common situation for solvated polypeptides. In addition, the amide
      I states in the terminal and turn regions were found to be delocalized over
      several neighboring amide units. Cross-peaks between the various labeled and
      unlabeled structural regions were clearly observed in the 2D IR correlation
      spectra, allowing them to be characterized for monitoring structural changes.
      These results illustrate the sensitivity of 2D IR to the local environment of
      solvated peptides. The simulated 1D and 2D IR spectra of the hairpin, obtained by
      using the vibrational exciton model incorporating coupling constants from quantum
      chemical computations and semiempirical calculations, were found to reproduce the
      essential features of the experimental results.

PMID- 16599538
TI  - Why pH titration in protein solutions follows a Hofmeister series.
AB  - Measurements of pH in single-phase cytochrome c suspensions are reported. The pH,
      as determined by a glass electrode, has a fixed value. With the addition of salt,
      the supposedly fixed pH changes strongly. The pH depends on salt type and
      concentration and follows a Hofmeister series. A theoretical interpretation is
      given that provides insights into such Hofmeister effects. These occur generally
      in protein solutions. While classical electrostatic models provide partial
      understanding of such trends in protein solutions, they fail to explain the
      observed ion specificity. Such models neglect electrodynamic fluctuation
      (dispersion) forces acting between ions and proteins. We use a Poisson-Boltzmann
      cell model that takes these ionic dispersion potentials between ions and proteins
      into account. The observed ion specificity can then be accounted for. Proteins
      act as buffers that display similar salt-dependent pH trends not previously
      explained.

PMID- 16599540
TI  - Oximetry of oxygen supersaturated solutions using nitroxides as EPR probe.
AB  - The broadening of the three hyperfine EPR nitroxide lines in oxygen
      supersaturated solutions was examined. The solutions were supersaturated with
      oxygen either by thermal decomposition of 1,4-peroxy-1,4-dimethylnaphthalene or
      by pressurizing molecular oxygen above the sample solution. The linear
      relationship between the Lorentzian component of the line width and the O(2)
      concentration was proven to hold even when the hyperfine splitting is unresolved.
      In this region of line broadening, the requirement for spectral simulation is
      discussed.

PMID- 16599539
TI  - Phosphonylation mechanisms of sarin and acetylcholinesterase: a model DFT study.
AB  - Potential energy surfaces for the phosphonylation of sarin and
      acetylcholinesterase (AChE) have been theoretically studied at the B3LYP/6
      311G(d,p) level of theory. The obtained results show that the phosphonylation
      process involves a two-step addition-elimination mechanism, with the first step
      (addition process) being the rate-determining step, while by comparison, the
      ensuing steps are very rapid. Stable trigonal bipyramidal intermediates are
      formed in the studied pathways. It is also revealed that the catalytic triad of
      acetylcholinesterase plays the catalytic role in the reaction by speeding up the
      phosphonylation process, as it does in the acylation reaction of ACh and AChE.
      The effect of aqueous solvation was accounted for via the polarizable continuum
      model. It is concluded that the enzymatic reaction here is influenced strongly by
      the solvent environment.

PMID- 16599541
TI  - Modeling the cycles of growth and detachment of bubbles in carbonated beverages.
AB  - In this paper, a model for the formation of bubbles in carbonated beverages is
      presented. It has previously been shown that bubbles form from cellulose fibers
      within such beverages and the passage of such bubbles from the fibers to the
      liquid surface has been modeled. A model is thus presented here that considers
      the process of formation, which is governed by diffusion through the fiber and
      bubble surfaces. The model comprises two stages, growth and detachment, and it is
      shown here that both play an important role. The latter process is found to occur
      over a much shorter time scale than the former, enabling the models to be
      partially decoupled. The total number of bubbles released from individual fibers
      over time is found to be approximated well by an exponential relationship, and
      the parameters in this relationship are presented for a range of different
      detachment angles and fiber sizes. It is found that bubble formation is promoted
      in narrow, long tubes, but that the time constant is solely determined by the
      rate of diffusion across the liquid surface. The surface tension is found to have
      minimal influence on the number of bubbles produced.

PMID- 16599542
TI  - Selective inhibition of paraffin deposition under high flow rate as a function of
      the crude oil paraffin type and content by fluorescence depolarization:
      polypropylene and high-density polyethylene.
AB  - High-density polyethylene (HDPE) and polypropylene (PP) were studied to identify
      tailor-made materials for walls of pipelines and ducts for crude paraffinic oil
      that inhibit paraffin depositions. The interfacial interaction was investigated
      from 50 to 70 degrees C and as a function of the n-C(36)H(74) paraffin
      concentration added to the paraffinic crude oil. The static and the dynamic
      interfacial tensions were observed, respectively, by traditional contact angle
      measurements and by fluorescence depolarization of the natural fluorescent probes
      of the crude oil, flowing at a high rate. The static interaction showed a low
      dependence on the n-paraffin content for both surfaces. For PP, it decreased
      slightly as the n-paraffin concentration increased, evidencing an increase in the
      liquid-liquid interaction. The dynamic interfacial tension with PP clearly
      decreased as temperature and n-paraffin concentration increased, the latter
      effect being attributed to the PP methyl groups hindering the interaction between
      the n-paraffin and the PP main chain. For the flow on HDPE, the interaction
      proved to be highly dependent on the n-paraffin concentration and temperature. It
      increased as n-paraffin was added and temperature decreased. The former effect is
      attributed to the alignment of the n-paraffin chains within the high rate flowing
      liquid and the similar molecular geometry of the n-paraffin and the linear
      polymer surface (almost without branches), which increases the number of sites
      available for interaction. PP proved to be more suitable for transportation of
      crude oil rich in paraffins with more than 36 carbon atoms, while HDPE was more
      suitable for those with smaller paraffinic chains.

PMID- 16599543
TI  - Role of manganese oxide octahedral molecular sieves in styrene epoxidation.
AB  - Manganese oxide octahedral molecular sieves having 2 x 2 tunnel structure (OMS-2)
      and synthesized by different methods were used for studying styrene oxidation
      with tert-butyl hydroperoxide (TBHP) as the oxidant. The catalytic activity of
      the as-synthesized OMS-2 materials was investigated. The physical and chemical
      properties of the OMS-2 materials are related to their activity in styrene
      oxidation. This particular study emphasizes the acid-base properties and the
      porous nature of these materials, and their role in styrene oxidation. Results of
      styrene oxidation reveal that acidity coupled with high porosity play a crucial
      role in these catalytic reactions. A desired acidity coupled with pore volume
      found in OMS-2 synthesized by reflux methods (OMS-2(R)) and high-temperature
      methods (OMS-2(HT)) produces materials with higher styrene conversion and styrene
      oxide selectivity when compared with OMS-2 synthesized by solvent free (OMS
      2(S)), microwave (OMS-2(MW)), or hydrothermal methods (OMS-2(HY)). Transition
      metal doped OMS-2 catalysts show better selectivity of styrene oxide when
      compared to their undoped catalysts.

PMID- 16599544
TI  - Critical coagulation concentration of a salt-free colloidal dispersion.
AB  - Both exact and approximate analytical solutions of the Poisson-Boltzmann equation
      for two planar, parallel surfaces are derived for the case when a dispersion
      medium contains counterions only, and the results obtained are used to evaluate
      the critical coagulation concentration of a spherical dispersion. A correction
      factor, which is a function of the valence of counterions, the surface potential
      of a particle, and the potential on the midplane between two particles at the
      onset of coagulation, is derived to modify the classic Schulze-Hardy rule for the
      dependence of the critical coagulation concentration on the valence of
      counterions. The correction factor is found to increase with the increase in the
      valence of counterions and/or with the increase in the surface potential.
      However, it approaches a constant value of 0.8390 if the surface potential is
      sufficiently high.

PMID- 16599545
TI  - Basic concepts in Q membrane chromatography for large-scale antibody production.
AB  - The large-scale production of recombinant human monoclonal antibodies demands
      economical purification processes with high throughputs. In this article we
      briefly describe a common antibody process and evaluate the Q membrane adsorber
      for process-scale antibody production as an alternative to a Q-packed-bed column
      in a flow-through mode. The scientific concepts underlining Q membrane technology
      and its application are reviewed. The disadvantages and advantages of using Q
      membrane chromatography as a purification unit in large-scale production are
      discussed, including problems initially seen with the Q membrane scale-down model
      but solved with the invention of a new scale-down model. The new Q-membrane unit
      operation has a process capacity greater than 3,000 g/m(2) or 10.7 kg/L with a
      LRV over 5 for four model viruses. In this Review, a cost analysis illustrates
      that Q membrane chromatography is a viable alternative to Q column chromatography
      as a polishing step in a flow-through mode for process-scale antibody production.

PMID- 16599546
TI  - Heterologous expression of Vitreoscilla hemoglobin (VHb) and cultivation
      conditions affect the alkaloid profile of Hyoscyamus muticus hairy roots.
AB  - Fast-growing hairy root cultures of Hyoscyamus muticus induced by Agrobacterium
      rhizogenes offer a potential production system for tropane alkaloids. Oxygen
      deficiency has been shown to limit growth and biomass accumulation of hairy
      roots, whereas little experimental data is available on the effect of oxygen on
      alkaloid production. We have investigated the effect of Vitreoscilla hemoglobin
      (VHb) expression and cultivation conditions on the complete alkaloid profile of
      H. muticus hairy roots in shake flasks and in a laboratory scale bioreactor. We
      optimized the growth medium composition and studied the effects of sucrose,
      ammonium, nitrate, and phosphate on growth and alkaloid production. Maximum
      biomass accumulation was achieved with the highest and maximum hyoscyamine
      content with the lowest sucrose concentration. The optimum nitrate concentration
      for growth was higher for the VHb line than the control. Neither VHb expression
      nor aeration improved the hyoscyamine content significantly, thus suggesting that
      hyoscyamine biosynthesis is not limited by oxygen availability. Interestingly,
      the effect of VHb expression on the alkaloid profile was slightly different from
      that of aeration. VHb expression did not affect the concentrations of
      cuscohygrine, which was increased by aeration. Therefore, the effect of VHb is
      probably not related only to its ability to increase the intracellular effective
      oxygen concentration.

PMID- 16599547
TI  - Measurement and analysis of intracellular ATP levels in metabolically engineered
      Zymomonas mobilis fermenting glucose and xylose mixtures.
AB  - Intracellular adenosine-5'-triphosphate (ATP) levels were measured in a
      metabolically engineered Zymomonas mobilis over the course of batch fermentations
      of glucose and xylose mixtures. Fermentations were conducted over a range of pH
      (5-6) in the presence of varying initial amounts of acetic acid (0-8 g/L) using a
      10% (w/v) total sugar concentration (glucose only, xylose only, or 5% glucose/5%
      xylose mixture). Over the design space investigated, ethanol process yields
      varied between 56.6% and 92.3% +/- 1.3% of theoretical, depending upon the test
      conditions. The large variation in process yields reflects the strong effect pH
      plays in modulating the inhibitory effect of acetic acid on fermentation
      performance. A corresponding effect was observed on maximum cellular specific
      growth rates, with the rates varying between a low of 0.15 h(-1) observed at pH 5
      in the presence of 8 g/L acetic acid to a high of 0.32 +/- 0.02 h(-1) obtained at
      pH 5 or 6 when no acetic acid was initially present. While substantial
      differences were observed in intracellular specific ATP concentration profiles
      depending upon fermentation conditions, maximum intracellular ATP accumulation
      levels varied within a relatively narrow range (1.5-3.8 mg ATP/g dry cell mass).
      Xylose fermentations produced and accumulated ATP at much slower rates than mixed
      sugar fermentations (5% glucose, 5% xylose), and the ATP production and
      accumulation rates in the mixed sugar fermentations were slightly slower than in
      glucose fermentations. Results demonstrate that higher levels of acetic acid
      delay the onset and influence the extent of intracellular ATP accumulation. ATP
      production and accumulation rates were most sensitive to acetic acid at lower
      values of pH.

PMID- 16599548
TI  - Engineering the E. coli UDP-glucose synthesis pathway for oligosaccharide
      synthesis.
AB  - A metabolic engineering strategy was successfully applied to engineer the UDP
      glucose synthesis pathway in E. coli. Two key enzymes of the pathway,
      phosphoglucomutase and UDP-glucose pyrophosphorylase, were overexpressed to
      increase the carbon flux toward UDP-glucose synthesis. When additional enzymes (a
      UDP-galactose epimerase and a galactosyltransferease) were introduced to the
      engineered strain, the increased flux to UDP-glucose synthesis led to an enhanced
      UDP-galactose derived disaccharide synthesis. Specifically, close to 20 mM UDP
      galactose derived disaccharides were synthesized in the engineered strain,
      whereas in the control strain only 2.5 mM products were obtained, indicating that
      the metabolic engineering strategy was successful in channeling carbon flux (8
      fold more) into the UDP-glucose synthesis pathway. UDP-sugar synthesis and
      oligosaccharide synthesis were shown to increase according to the enzyme
      expression levels when inducer concentration was between 0 and 0.5 mM. However,
      this dependence on the enzyme expression stopped when expression level was
      further increased (IPTG concentration was increased from 0.5 to 1 mM), indicating
      that other factors emerged as bottlenecks of the synthesis. Several likely
      bottlenecks and possible engineering strategies to further improve the synthesis
      are discussed.

PMID- 16599549
TI  - Relationship between Debaryomyces pseudopolymorphus enzymatic extracts and
      release of terpenes in wine.
AB  - As a result of the interest that exists in the liberation of aromas in young
      wines, we obtained some different enzymatic extracts (purified extract, P;
      lyophilized purified extract, LP; immobilized purified extract, IP; and
      immobilized lyophilized purified extract, ILP) with beta-glucosidase activity
      from Debaryomyces pseudopolymorphus, which excreted the enzyme in the growth
      medium. The extracts were added to natural glycosides isolated from different
      grape varieties. The results were compared with the effect of seven commercial
      enzyme preparations (CEP), obtained from molds used in wine making. It was shown
      that some yeast extracts had effects similar to those of the CEP, and the next
      step was to use them on wine samples elaborated in the laboratory. The effect was
      studied at 9 and 16 days of contact, quantifying both the precursors that were
      retained and the liberated terpenes. The results were compared with a control
      wine (without any extract) and with wine treated with a commercial enzyme
      preparation specially indicated for the liberation of aromas. It was observed
      that the enzymatic extracts from Db. pseudopolymorphus hydrolyzed the precursors
      in wine and that they could compete with the commercial preparations since the
      liberation was produced in even less time.

PMID- 16599550
TI  - High-level expression of a soluble functional antimicrobial peptide, human beta
      defensin 2, in Escherichia coli.
AB  - In this work, taking human beta-defensin-2 (HBD2) as a demonstrative molecule,
      the strategies for high efficient production of functional human beta-defensins
      in E. coli were studied. Fusion mature HBD2 (TrxA-mHBD2) showed high solubility
      and productivity without the need for lowering the cultivation temperature. The
      solubility of target fusion protein could attain 81.3% even at 37 degrees C with
      a volumetric productivity as high as 235 mg/L in a rich medium MBL at the same
      temperature and reached 346 mg/L at 28 degrees C. The His-Tag in the fusion
      protein enabled the application of affinity chromatography separation to obtain
      high purity of the overexpressed recombinant fusion protein. After digestion by
      enterokinase, purification via cationic exchange chromatography, and desalting by
      ultrafiltration, mature HBD2 product was obtained with a purity of 95% in an
      overall recovery of 29.2%. The antimicrobial activity of the recombinant mature
      HBD2 and the influence factors were tested using E. coli K12D31 as a sensitive
      strain.

PMID- 16599551
TI  - Conditioned medium from Listeria innocua stimulates emergence from a resting
      state: not a response to E. coli quorum sensing autoinducer AI-2.
AB  - The lag phase of the bacterial growth curve is an important determinant in
      speeding the detection of pathogens. It is affected by many factors including the
      prevailing growth environment and inoculum size, as well as specific signal
      molecules. The elucidation of growth-regulating signal molecules is further
      facilitated by culturing cells in defined growth media. In this study, a defined
      medium capable of supporting growth of Listeria innocua at similar levels as
      obtained using a complex brain heart infusion (BHI) media was developed. Further,
      the effects of conditioned medium (CM) on population lag time of L. innocua was
      investigated using a rapid parallel approach (with an automated microtiter plate
      reader). Importantly, the lag phase was shortened by up to approximately 50% by
      the addition of CM from L. innocua cultures obtained late in the exponential
      phase. Finally, while L. innocua were found to secrete bacterial signaling
      autoinducer, AI-2, tests using Escherichia coli based CM having a 90-fold
      difference in AI-2 level suggested that the observed decrease in lag phase was
      not due to E. coli-derived AI-2 and was instead due to elements specific to L.
      innocua. These findings indicate secreted signal molecules may be found in CM
      that speed detection of L. innocua.

PMID- 16599552
TI  - Effects of conditioned medium factors and passage number on Sf9 cell physiology
      and productivity.
AB  - The effects of conditioned medium (CM) and passage number on Spodoptera
      frugiperda Sf9 cell physiology and productivity have been studied. Low passage
      (LP) cells at passages 20-45 were compared to high passage (HP) cells at passages
      >100. Addition of 20% CM or 10 kDa filtrated CM to LP cells promoted growth. LP
      cells passed a switch in growth kinetics, characterized by a shorter lag phase
      and a higher growth rate, after 30-40 passages. After this point, CM lost its
      stimulating effect on proliferation. HP cells displayed a still shorter lag phase
      and reached the maximum cell density 24-48 earlier than LP cells. HP cells also
      exhibited higher specific productivity of recombinant protein compared to LP
      cells, when infected with baculovirus during the initial 48 h of culture. The
      specific productivity of LP cells was decreased by 30-50% by addition of 20% CM
      or 10 kDa filtrated CM, whereas addition of CM to cells having passed the switch
      in growth kinetics had no negative effect on productivity. Cell cycle analysis
      showed that a large proportion of HP cells, >60%, was transiently arrested in
      G2/M after inoculation. In LP cultures this proportion was lower, 40-45%, and
      addition of CM decreased the arrested population further. This correlated to the
      cell size, the HP cells being the largest: HP cells > LP > LP + 20% CM > LP + 20%
      10 kDa filtrated CM. Since the degree of synchronization in G2/M correlated to
      the productivity, yeastolate limitation was used to achieve 85% G2/M synchronized
      cells. In this culture the specific productivity was maintained during a
      prolonged production phase and a 69% higher volumetric yield was obtained. The
      results suggest that a decreasing degree of synchronization during the course of
      culture partly explains the cell-density-dependent drop in productivity in Sf9
      cells.

PMID- 16599553
TI  - Screening and characterization of affinity peptide tags specific to polystyrene
      supports for the orientated immobilization of proteins.
AB  - Dodecapeptides that exhibit a high affinity specific to a polystyrene surface (PS
      tags) were screened using an Escherichia coli random peptide display library
      system, and the compounds were used as a peptide tag for the site-specific
      immobilization of proteins. The various PS-tags obtained after 10 rounds of
      biopanning selection were mainly composed of basic and aliphatic amino acid
      residues, most of which were arranged in close proximity to one another. Mutant
      type glutathione S-transferases (GSTs) fused with the selected PS-tags, PS19
      (RAFIASRRIKRP) and PS23 (AGLRLKKAAIHR) at their C-terminus, GST-PS19 and GST
      PS23, when adsorbed on the PS latex beads had a higher affinity than the wild
      type GST, and the specific remaining activity of the immobilized mutant-type GSTs
      was approximately 10 times higher than that of the wild-type GST. The signal
      intensity detected for GST-PS19 and GST-PS23 adsorbed on hydrophilic and
      hydrophobic PS surfaces using an anti-peptide antibody specific for the N
      terminus peptide of GST was much higher than that for the wild-type GST. These
      findings indicate that the mutant-type GSTs fused with the selected peptide tags,
      PS19 and PS23, could be site-specifically immobilized on the surface of
      polystyrene with their N-terminal regions directed toward the solution. Thus, the
      selected peptide tags would be useful for protein immobilization in the
      construction of enzyme-linked immunosorbent assay (ELISA) systems and protein
      based biochips.

PMID- 16599554
TI  - Enhanced biodegradation of toxic organophosphate compounds using recombinant
      Escherichia coli with sec pathway-driven periplasmic secretion of
      organophosphorus hydrolase.
AB  - Although Escherichia coli can be genetically engineered to degrade environmental
      toxic organophosphate compounds (OPs) to nontoxic materials, a critical problem
      in such whole cell systems is limited substrate diffusion. The present work
      examined whether periplasmic expression of organophosphorus hydrolase (OPH)
      resulted in better whole cell enzymatic activity compared to standard cytosolic
      expression. Recombinant OPH periplasmic expression was achieved using the general
      secretory (sec) pathway with the pelB signal sequence. We found that while total
      OPH activity in periplasmic-expressing cell lysates was lower compared to that in
      cytosolic-expressing cell lysates whole cell OPH activity was 1.8-fold greater at
      12 h post-induction in the periplasmic-expressing cells as a result of OPH
      translocation into the periplasmic space ( approximately 67% of whole cell OPH
      activity was found in the periplasmic fraction). These data suggest that E. coli
      engineered to periplasmically secrete OPH via the sec pathway may provide an
      improved whole cell biodegradation system for destruction of environmental toxic
      OPs.

PMID- 16599555
TI  - Effects of pH strategy on endo- and exo-metabolome profiles and sodium potassium
      hydrogen ports of beta-lactamase-producing Bacillus licheniformis.
AB  - The effects of pH strategy on endo- and exo-metabolome profiling of beta
      lactamase-producing Bacillus licheniformis were investigated at controlled-pH
      (pH(C) = 6.5, 6.75, 7.0, 7.25, 7.5) and uncontrolled-pH (pH(UC) = 7.5) values
      using a glucose-based defined medium. The cell concentration profiles were not
      affected by the pH considerably within the investigated range. The highest enzyme
      activities were obtained as A = 54 U cm(-)(3) at pH(C) = 6.75 among the
      controlled-pH operations and as A = 57 U cm(-3) at the uncontrolled-pH pH(UC) =
      7.5. At all conditions, oxygen transfer resistances were more effective, whereas
      the limitation increased in the beta-lactamase production phase. Total
      intracellular amino acid concentrations ranged between 0.142 and 6.766 kg m(-3)
      (0.0058-0.277 g g(cell)(-1)), and their concentrations in terms of kg m(-3) were,
      at most, 580-fold higher than the extracellular concentrations.
      Methionine/cysteine concentrations were generally higher than the other
      intracellular amino acids, whereas asparagine concentration was the highest in
      the fermentation broth. From Na(+), K(+), and H(+) ion profiles, Na(+)-K(+)
      antiport and Na(+)-H(+) symport were found to be present within the system, and a
      correlation was found between organic acid transport and Na(+)-H(+) symport.
      Intracellular organic acid concentrations in terms of kg m(-3) were, at most, 20
      fold higher than that of the extracellular, and with the increase in pH,
      extracellular acetic acid concentration increased and lactic acid concentration
      decreased. Average permeability coefficient values of organic acids were found to
      be in the range from 4.10 x 10(-7) to 4.32 x 10(-6) cm s(-1) for the growth phase
      (0 < t < 6 h) and decreased at least 3-fold in the beta-lactamase production
      phase (8 < t < 15 h), indicating the considerable structural change of the lipid
      membrane during the fermentation.

PMID- 16599557
TI  - Laccase-mediated oxidative degradation of the herbicide dymron.
AB  - The present study reports the successful and effective degradation of the
      persistent herbicide dymron catalyzed by the oxidative enzyme laccase in the
      presence of a reaction mediator (a laccase/mediator system). Using 2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) as the mediator, over 90% of dymron
      was degraded within 24 h, while the half-life of dymron is 50 days in soil. The
      results suggested that oxidation of dymron resulted in the production of
      decomposed compounds with a single aromatic ring. We also found that edible
      surfactants and a dishwashing detergent were useful to solubilize dymron in an
      aqueous solution and did not inhibit the oxidative degradation. Degradation
      proceeded at acidic pH and in a broad range of temperatures (303-353 K). The use
      of natural mediators also allowed the oxidative degradation of dymron to some
      extent. In conclusion, we propose the possible use of a laccase/mediator system
      for the treatment of soils and drainwater contaminated with herbicides.

PMID- 16599556
TI  - Effect of overexpression of a soluble pyridine nucleotide transhydrogenase (UdhA)
      on the production of poly(3-hydroxybutyrate) in Escherichia coli.
AB  - A soluble pyridine nucleotide transhydrogenase (UdhA) has been used to increase
      the productivity and yield of PHB in vivo. By inducing a high level of UdhA,
      which can transfer reducing equivalents between NAD and NADP, we have increased
      NADPH availability, resulting in high yield and productivity of PHB in
      Escherichia coli. Coexpression of the phb operon from Alcaligenes eutrophus H16
      and the native udhA from E. coli from high copy plasmids resulted in an increase
      in PHB yield from 49 to 66% g of PHB per gram of total cell dry weight and an
      increase in final concentration from 3.52 to 6.42 g/L; the PHB concentration of
      the udhA carrying strain is almost twice that of the control strain expressing
      only the phb operon. The results of this study demonstrate the effectiveness of
      cofactor manipulation and its application as a tool in metabolic engineering.

PMID- 16599558
TI  - Modeling and optimization of photosynthetic hydrogen gas production by green alga
      Chlamydomonas reinhardtii in sulfur-deprived circumstance.
AB  - Biological hydrogen production by the green alga Chlamydomonas reinhardtii under
      sulfur-deprived conditions has attracted great interest due to the fundamental
      and practical importance of the process. The photosynthetic hydrogen production
      rate is dependent on various factors such as strain type, nutrient composition,
      temperature, pH, and light intensity. In this study, physicochemical factors
      affecting biological hydrogen production by C. reinhardtii were evaluated with
      response surface methodology (RSM). First, the maximum specific growth rate of
      the alga associated with simultaneous changes of ammonium, phosphate, and sulfate
      concentrations in the culture medium were investigated. The optimum conditions
      were determined as NH(4+) 8.00 mM, PO(4)(3-) 1.11 mM, and SO(4)(2-) 0.79 mM in
      Tris-acetate-phosphate (TAP) medium. The maximum specific growth rate with the
      optimum nutrient concentrations was 0.0373 h(-1). Then, the hydrogen production
      rate of C. reinhardtii under sulfur-deprivation conditions was investigated by
      simultaneously changing two nutrient concentrations and pH in the medium. The
      maximum hydrogen production was 2.152 mL of H(2) for a 10-mL culture of alga with
      density of 6 x 10(6) cells mL(-1) for 96 h under conditions of NH(4)(+) 9.20 mM,
      PO(4)(3-) 2.09 mM, and pH 7.00. The obtained hydrogen production rate was
      approximately 1.55 times higher than that with the typical TAP medium under
      sulfur deficiency.

PMID- 16599559
TI  - Role of carbonyl cyanide m-chlorophenylhydrazone in enhancing photobiological
      hydrogen production by marine green alga Platymonas subcordiformis.
AB  - We demonstrated that a significant volume of H(2) gas could be photobiologically
      produced by a marine green alga Platymonas subcordiformis when an uncoupler of
      photophosphorylation, carbonyl cyanide m-chlorophenylhydrazone (CCCP), was added
      after 32 h of anaerobic dark incubation, whereas a negligible volume of H(2) gas
      was produced without CCCP. The role of CCCP in enhancing photobiological H(2)
      production was delineated. CCCP as an ADRY agent (agent accelerating the
      deactivation reactions of water-splitting enzyme system Y) rapidly inhibited the
      photosystem II (PSII) activity of P. subcordiformis cells, resulting in a
      markedly decline in the coupled oxygen evolution. The mitochondrial oxidative
      respiration was only slightly inactivated by CCCP, which depleted O(2) in the
      light. As a result, anaerobiosis during the stage of photobiological H(2)
      evolution was established, preventing severe O(2) inactivation of the reversible
      hydrogenase in P. subcordiformis. The uncoupling effect of CCCP accelerates
      electron transfer from water due to a disruption of the proton motive force and
      release of DeltapH across the thylakoid membrane and thus enhances the
      accessibility of electron and H(+) to hydrogenase. The electrons for hydrogen
      photoevolution are mainly from the photolysis of water (90%). Upon the addition
      of CCCP, Chl a/b ratio increased, which implies a decrease in the light
      harvesting PSII antennae or an increase in PSII/PSI ratio, possibly resulting in
      higher efficiency of utilization of light energy. The enhancement of H(2)
      evolution by the addition of CCCP is mostly due to the combination of the above
      three mechanisms. However, the disruption of the proton gradient across the
      thylakoid membrane may prevent a sustained photobiological H(2) evolution due to
      a shortfall of ATP generation essential for the maintenance and repair functions
      of the cells.

PMID- 16599560
TI  - Lipase-catalyzed transformations for the synthesis of butyl lactate: a comparison
      between esterification and transesterification.
AB  - The alpha-hydroxy esters are increasingly employed in cosmetic, food, and
      pharmaceutical formulations as they determine reduced skin-irritant effects in
      comparison with the respective acids, offering similar hygroscopic, emulsifying,
      and exfoliating properties. The enzymatic synthesis of lactate esters in
      nonaqueous systems was studied as regards the influence of the critical process
      parameters, to enable a comparison between the most commonly used synthetic
      routes, namely, esterification and transesterification. The experimental results
      showed that the direct esterification of lactic acid with butanol may be limited
      by the reduced lipase stability in the presence of the acid (substrate) and of
      the water (product), in particular when solvent-free media are used. The
      stability of the enzyme is further reduced as polar solvents are required as a
      result of the polarity of the lactic acid. Therefore, the use of the lactic acid
      as substrate is of practical interest only when the acid is significantly cheaper
      in comparison with its short-chain esters. If this is not the case, the
      transesterification of the ethyl lactate with butanol is to be preferred for the
      higher flexibility in the choice of the experimental conditions, the operability
      of solvent-free systems, and the simplicity of the product removal assembly.

PMID- 16599561
TI  - Ethanol production from alkaline peroxide pretreated enzymatically saccharified
      wheat straw.
AB  - Wheat straw used in this study contained 44.24 +/- 0.28% cellulose and 25.23 +/-
      0.11% hemicellulose. Alkaline H(2)O(2) pretreatment and enzymatic
      saccharification were evaluated for conversion of wheat straw cellulose and
      hemicellulose to fermentable sugars. The maximum yield of monomeric sugars from
      wheat straw (8.6%, w/v) by alkaline peroxide pretreatment (2.15% H(2)O(2), v/v;
      pH 11.5; 35 degrees C; 24 h) and enzymatic saccharification (45 degrees C, pH
      5.0, 120 h) by three commercial enzyme preparations (cellulase, beta-glucosidase,
      and xylanase) using 0.16 mL of each enzyme preparation per g of straw was 672 +/-
      4 mg/g (96.7% yield). During the pretreatment, no measurable quantities of
      furfural and hydroxymethyl furfural were produced. The concentration of ethanol
      (per L) from alkaline peroxide pretreated enzyme saccharified wheat straw (66.0
      g) hydrolyzate by recombinant Escherichia coli strain FBR5 at pH 6.5 and 37
      degrees C in 48 h was 18.9 +/- 0.9 g with a yield of 0.46 g per g of available
      sugars (0.29 g/g straw). The ethanol concentration (per L) was 15.1 +/- 0.1 g
      with a yield of 0.23 g/g of straw in the case of simultaneous saccharification
      and fermentation by the E. coli strain at pH 6.0 and 37 degrees C in 48 h.

PMID- 16599562
TI  - Study on mesophilic and thermophilic alcohol dehydrogenases in gas-phase
      reaction.
AB  - The initial reaction rate and the thermostability of the mesophilic alcohol
      dehydrogenase (ADH) from Lactobacillus brevis (LBADH), and the thermophilic ADH
      from Thermoanaerobacter sp. (ADH T) in gas-phase reaction were compared. The
      effects of water activity, cofactor-to-protein molar ratio, and reaction
      temperature on the reduction of acetophenone to 1-phenylethanol were studied. An
      optimal water activity of 0.55 in terms of productivity was found for both ADHs.
      The cofactor-to-protein molar ratio was chosen slightly higher than equimolar to
      increase both activity and thermostability. An excellent optimal productivity of
      1,000 g x L(-1) x d(-1) for LBADH and 600 g x L(-1) x d(-1)for ADH T was found at
      60 degrees C, while the highest total turnover numbers with respect to the enzyme
      were achieved at 30 degrees C and amounted to 4.2 million for LBADH and 1.7
      million for ADH T, respectively. Interestingly, the ADH from the mesophilic L.
      brevisshowed the higher thermostability in the nonconventional medium gas phase.

PMID- 16599563
TI  - Optimal preparation of immobilized liposome-bound cellulase for hydrolysis of
      insoluble cellulose in an external loop airlift bioreactor.
AB  - Immobilized liposome-bound cellulase (ILC) was optimally prepared for the ILC
      catalyzed hydrolysis of insoluble cellulose in an external loop airlift
      bioreactor. The liposomes with mean diameters of 200, 100, and 50 nm were used to
      prepare three kinds of ILCs, i.e., ILC(200), ILC(100) and ILC(50), respectively.
      The activity and stability of ILC(100) were examined with soluble cellulose (CMC)
      in addition to the insoluble substrate of cellulose powder (CC31) in a shaking
      flask as well as the airlift bioreactors. The experiments were carried out with
      45 degrees C and pH 4.8 being found to be optimal for the activity. The activity
      of ILC(100) was stable in either airlift or shaking flask bioreactor during the
      five times repeated hydrolyses of CC31 corresponding to a total reaction time of
      240 h. This confirmed that the cellulase molecules were covalently bonded to the
      liposomes covalently bound to the chitosan gel beads. Nevertheless, the activity
      of ILC(100) with CMC steadily decreased throughout the repeated reactions,
      suggesting an adverse effect of CMC on the ILC(100) activity. Among the three
      ILCs, ILC(50) was found to be the most stable and productive biocatalyst during
      the repeated hydrolyses of insoluble CC31 in the airlift bioreactor. More than
      70% of the initial activity of ILC(50) was retained even after the six times
      repeated reactions for 288 h. Conversely, the ILC(200) was found to be the most
      unstable catalyst. Such a difference in stability among these ILCs was suggested
      to be caused by the difference in physical stability of their liposome membranes
      to the liquid shear stress due to the rising bubbles and circulating liquid as
      well as that in the amount of the cellulase molecules unstably incorporated in
      the membranes. ILC(50) was thus shown to have the most potential for an efficient
      hydrolysis of insoluble cellulose in a practical airlift bioreactor.

PMID- 16599564
TI  - Sterilizing filtration of plasmid DNA: effects of plasmid concentration,
      molecular weight, and conformation.
AB  - Plasmid DNA purification development has been driven by the increased need for
      large quantities of highly purified, sterile plasmid DNA for clinical studies.
      Detailed characterization and development of the terminal sterile filtration
      process step is often limited due to time constraints and the scarcity of
      sufficient quantities of purified plasmid. However, the large size of the plasmid
      molecule and variations in conformation can lead to significant yield losses if
      this process step is not optimized. In this work, the gradual pore-plugging model
      of flow decay was found to be valid for plasmid DNA by using an ultra scaledown
      apparatus (1-4 cm(2) filter area). Filtration capacity was found to be
      insensitive to pressure. Multiple filter types were screened and both source and
      composition of materials were found to affect filter capacity dramatically. The
      filter capacity for plasmid was improved by increasing plasmid concentrations as
      well as by modifying buffer conditions to reduce the apparent size of the
      plasmid. Filtration capacities varied over a greater than 2 log range when
      plasmids with sizes ranging from 5.5 to 11 kb and supercoiled plasmid content of
      55-95% were explored. Larger plasmids and feeds with lower supercoiled contents
      led to reduced capacities. These results can be used to define conditions for
      scale-up of plasmid sterile filtration, as evidenced by processing a 30 g lot
      using a filtration area of 1,000 cm(2), with a 96% yield, based on filtration
      capacity data from 4 cm(2) test filters.

PMID- 16599565
TI  - Capture of bacteria from fermentation broth by body feed filtration: a solved
      problem?
AB  - The direct capture of bacteria produced in high cell density fermentation by
      filtration is not possible once the milliliter-scale has been surpassed.
      Filtration in the presence of a filter aid (body feed filtration) constitutes a
      putative and scalable alternative, but only if conditions proposed by industry
      for large-scale filtration processes, namely, flow rates (for aqueous solutions)
      in the range of 500-1,500 L/(m(2) x h) and a filter aid concentration of <or=20
      g/L, can be met. To this end several filter aids (grades of cellulose,
      diatomaceous earth, mixes thereof) were tested, albeit with no success. Capture
      and retention of bacteria was low (not possible in the case of cellulose), and
      the produced filter cakes were unstable and of low permeability. In the case of
      the diatomaceous earth close to 100% bacterial capture was possible, but only
      with filter aid concentrations that were 1 order of magnitude above the proposed
      limit. By using flocculating agents (Fe(3+)/Al(3+), PEI) either alone or in
      combination with diatomaceous earth and also the use of positively charged
      cellulose, bacteria capture could be achieved from several liters of cell
      suspension (OD(600) <or= 15) in filtration experiments adhering to the industrial
      recommendations. However, the bacteria were only weakly retained in such cakes
      and easily released by sudden pressure pulses. Satisfactory results were only
      obtained by filtration of the bacteria suspension at slightly alkaline pH (8.0,
      50 mM Tris buffer) after treatment with sodium-activated bentonite (5 g/L) and
      PEI (50 mg/L) in the presence of 250 mM NaCl. In such cases 100% of the bacteria
      could reproducibly be captured in a filtration using 20 g/L of diatomaceous earth
      as filter aid. The thus produced filter cakes strongly retained the bacteria and
      showed good filtration performance. The procedure is at present limited to E.
      coli culture with biomass contents of OD(600) <or= 15. Cultures with higher
      OD(600) have to be diluted prior to filtration.

PMID- 16599566
TI  - Effect of membrane charge on flow and protein transport during ultrafiltration.
AB  - Although several recent studies have demonstrated the importance of electrostatic
      interactions in ultrafiltration, there have been few quantitative studies of the
      effects of membrane charge density on protein transport and membrane hydraulic
      permeability. Data were obtained using a series of charge-modified cellulose
      membranes, with the surface charge density controlled by varying the extent of
      addition of a quaternary amine functionality. The membrane charge was evaluated
      from streaming potential measurements. Protein transmission decreased by a factor
      of 100 as the membrane zeta potential increased from 0.3 to 6.6 mV. The protein
      sieving data were in good agreement with a partitioning model accounting for
      electrostatic effects, while the hydraulic permeability data were consistent with
      a flow model accounting for the effects of counter-electroosmosis. The results
      provide the first quantitative analysis of the effects of membrane charge density
      on the performance of ultrafiltration membranes.

PMID- 16599567
TI  - Efficiency of new fungal cellulase systems in boosting enzymatic degradation of
      barley straw lignocellulose.
AB  - This study examined the cellulytic effects on steam-pretreated barley straw of
      cellulose-degrading enzyme systems from the five thermophilic fungi Chaetomium
      thermophilum, Thielavia terrestris, Thermoascus aurantiacus, Corynascus
      thermophilus, and Myceliophthora thermophila and from the mesophile Penicillum
      funiculosum. The catalytic glucose release was compared after treatments with
      each of the crude enzyme systems when added to a benchmark blend of a commercial
      cellulase product, Celluclast, derived from Trichoderma reesei and a beta
      glucosidase, Novozym 188, from Aspergillus niger. The enzymatic treatments were
      evaluated in an experimental design template comprising a span of pH (3.5-6.5)
      and temperature (35-65 degrees C) reaction combinations. The addition to
      Celluclast + Novozym 188 of low dosages of the crude enzyme systems,
      corresponding to 10 wt % of the total enzyme protein load, increased the
      catalytic glucose yields significantly as compared to those obtained with the
      benchmark Celluclast + Novozyme 188 blend. A comparison of glucose yields
      obtained on steam-pretreated barley straw and microcrystalline cellulose, Avicel,
      indicated that the yield improvements were mainly due to the presence of highly
      active endoglucanase activity/activities in the experimental enzyme preparations.
      The data demonstrated the feasibility of boosting the widely studied T.
      reeseicellulase enzyme system with additional enzymatic activity to achieve
      faster lignocellulose degradation. We conclude that this supplementation strategy
      appears feasible as a first step in identifying truly promising fungal enzyme
      sources for fast development of improved, commercially viable, enzyme
      preparations for lignocellulose degradation.

PMID- 16599568
TI  - Protein refolding mediated by reverse micelles of Cibacron Blue F-3GA modified
      nonionic surfactant.
AB  - An affinity-based reverse micellar system formulated with nonionic surfactant was
      applied to the refolding of denatured-reduced lysozyme. The nonionic surfactant
      of sorbitan trioleate (Span 85) was modified with Cibacron Blue F-3GA (CB) as an
      affinity surfactant (CB-Span 85) to form affinity-based reverse micelles in n
      hexane. The water content of 15 was found optimal for lysozyme refolding in the
      reverse micellar system of 62.7 mmol/L Span 85 with coupled CB of 0.3 and 0.5
      mmol/L. In addition, the operating conditions such as pH and the concentrations
      of urea and redox reagents were optimized. Under the optimized conditions,
      complete renaturation of lysozyme at 3-3.5 mg/mL was achieved, whereas dilution
      refolding in the bulk aqueous phase under the same conditions gave much lower
      activity recovery. Moreover, the secondary structure of the refolded lysozyme was
      found to be the same as the native lysozyme. Over 95% of the refolded lysozyme
      was recovered from CB-Span 85 reverse micelles by a stripping solution of 0.5
      mol/L MgCl(2). Thus, the present system is advantageous over the conventional
      reverse micellar system formed with ionic surfactants in the ease of protein
      recovery.

PMID- 16599570
TI  - Synthesis of novel porous magnetic silica microspheres as adsorbents for
      isolation of genomic DNA.
AB  - An improved procedure is described for preparation of novel mesoporous
      microspheres consisting of magnetic nanoparticles homogeneously dispersed in a
      silica matrix. The method is based on a three-step process, involving (i)
      formation of hematite/silica composite microspheres by urea-formaldehyde
      polymerization, (ii) calcination of the composite particles to remove the organic
      constituents, and (iii) in situ transformation of the iron oxide in the
      composites by hydrogen reductive reaction. The as-synthesized magnetite/silica
      composite microspheres were nearly monodisperse, mesoporous, and magnetizable,
      with as typical values an average diameter of 3.5 microm, a surface area of 250
      m(2)/g, a pore size of 6.03 nm, and a saturation magnetization of 9.82 emu/g.
      These magnetic particles were tested as adsorbents for isolation of genomic DNA
      from Saccharomyces cerevisiae cells and maize kernels. The results are quite
      encouraging as the magnetic particle based protocols lead to the extraction of
      genomic DNA with satisfactory integrity, yield, and purity. Being hydrophilic in
      nature, the porous magnetic silica microspheres are considered a good alternative
      to polystyrene-based magnetic particles for use in biomedical applications where
      nonspecific adsorption of biomolecules is to be minimized.

PMID- 16599569
TI  - Optimization of reaction conditions for enzymatic viscosity reduction and
      hydrolysis of wheat arabinoxylan in an industrial ethanol fermentation residue.
AB  - This study examined enzyme-catalyzed viscosity reduction and evaluated the
      effects of substrate dry matter concentration on enzymatic degradation of
      arabinoxylan in a fermentation residue, "vinasse", resulting from industrial
      ethanol manufacture on wheat. Enzymatic catalysis was accomplished with a 50:50
      mixture of an enzyme preparation from Humicola insolens, Ultraflo L, and a
      cellulolytic enzyme preparation from Trichoderma reesei, Celluclast 1.5 L. This
      enzyme mixture was previously shown to exhibit a synergistic action on
      arabinoxylan degradation. The viscosity of vinasse decreased with increased
      enzyme dosage and treatment time at pH 5, 50 degrees C, 5 wt % vinasse dry
      matter. After 24 h of enzymatic treatment, 76-84%, 75-80%, and 43-47%,
      respectively, of the theoretically maximal arabinose, xylose, and glucose
      releases were achieved, indicating that the viscosity decrease was a result of
      enzyme-catalyzed hydrolysis of arabinoxylan, beta-glucan, and cellulose. In
      designed response surface experiments, the optimal enzyme reaction conditions
      with respect to pH and temperature of the vinasse, the vinasse supernatant
      (mainly soluble material), and the vinasse sediment (mainly insoluble substances)
      varied from pH 5.2-6.4 and 41-49 degrees C for arabinose release and from pH 4.9
      5.3 and 42-46 degrees C for xylose release. Even though only limited hydrolysis
      of the arabinoxylan in the vinasse sediment fraction was obtained, the results
      indicated that the same enzyme activities acted on the arabinoxylan in the
      different vinasse fractions irrespective of the state of solubility of the
      substrate material. The levels of liberated arabinose and xylose increased with
      increased dry matter concentration during enzymatic hydrolysis in the vinasse and
      the vinasse supernatant, but at the same time, increased substrate dry matter
      concentrations gave corresponding linear decreases in the hydrolytic efficiency
      as evaluated from levels of monosaccharide release per weight unit dry matter.
      The study thus documents that enzymatic arabinoxylan hydrolysis of the vinasse
      significantly decreases the vinasse viscosity and that a compromise in the dry
      matter must be found if enzymatic efficiency must be balanced with monosaccharide
      yields.

PMID- 16599571
TI  - Compaction agent protection of nucleic acids during mechanical lysis.
AB  - Mechanical lysis is an efficient and widely used method of liberating the
      contents of microbial cells, but the sensitivity of large nucleic acids to shear
      damage has prevented the application of mechanical lysis to DNA purification. It
      is demonstrated that polycationic compaction agents can protect DNA from shear
      damage and allow chromosomal and plasmid DNA purification by mechanical lysis. In
      addition to being substantially protected during mechanical lysis, the compacted
      DNA can be separated with the insoluble cell debris, washed, and selectively
      resolubilized, yielding a substantially purified DNA product. An additional
      benefit of this method is that lysate viscosity is greatly reduced, allowing the
      use of much smaller processing volumes when compared with traditional lysis
      methods used in nucleic acid purification.

PMID- 16599572
TI  - A heavy metal biotrap for wastewater remediation using poly-gamma-glutamic acid.
AB  - Poly-gamma-glutamic acid (gamma-PGA) obtained from Bacillus licheniformis ATCC
      9945 was evaluated as a potential biosorbent material for use in the removal of
      heavy metals from aqueous solution. Copper (Cu(2+)) was chosen as the model heavy
      metal used in these studies since it is extensively used by electroplating and
      other industries, has been the model for many other similar studies, and can be
      easily assayed through a number of convenient methods. Cu(2+)-gamma-PGA binding
      parameters under varying conditions of pH, temperature, ionic strength, and in
      the presence of other heavy metal ions were determined for the purified
      biopolymer using a specially designed dialysis apparatus. Applying the Langmuir
      adsorption isotherm model showed that gamma-PGA had a copper capacity approaching
      77.9 mg/g and a binding constant of 32 mg/L (0.5 mM) at pH 4.0 and 25 degrees C.
      Cu(2+)-gamma-PGA adsorption was relatively temperature independent between 7 and
      40 degrees C, while an increase in ionic strength led to a decrease in metal ion
      binding. Cd(2+) and Zn(2+) ions compete with Cu(2+) for binding sites on the
      gamma-PGA biopolymer. Metal uptake by gamma-PGA was further tested using a
      tangential flow filtration apparatus in a diafiltration mode in which metal was
      continually processed through a dilute solution of gamma-PGA without allowing for
      equilibrium to be established. The circulating polymer solution was able to
      complex metal as well as successfully prevent passage of unbound copper ions
      present in solution through the membrane. Using 500 mL of a 0.2% gamma-PGA
      solution, up to 97% of a 50 mg/L copper sulfate solution processed at a flow rate
      of 115 mL/min was retained by the polymer. For a 10 mg/L solution of Cu(2+) as
      copper sulfate, filtrate concentrations of Cu(2+) never rose above 0.6 mg/L while
      processing 2.5 L of dilute copper sulfate.

PMID- 16599573
TI  - Preparative fractionation of protein, RNA, and plasmid DNA using centrifugal
      precipitation chromatography with tubular dialysis membrane inside a convoluted
      tubing as separation channel.
AB  - Fractionation of clarified E. coli lysate components in bench-scale and
      preparative-scale centrifugal precipitation chromatography (CPC), using a
      solution of cationic surfactant cetyltrimethylammonium bromide (CTAB) containing
      0.5 M NaCl as precipitant, are compared here. Step gradient of CTAB from 0.50% to
      0.16% (w/v) gave a successful fractionation in bench-scale CPC; however, a linear
      gradient of lower CTAB concentration, 0.20-0% (w/v), was used in the preparative
      scale and resulted in similar fractionation. The preparative-scale CPC has a
      superior sample loading capacity by the use of tubular dialysis membrane inside
      convoluted tubing as the separation channel. In this study, the quantity of the
      sample loaded into the preparative CPC was about 15 times more than that in the
      bench scale, and in a single run the preparative CPC could prepare approximately
      3 mg of plasmid DNA with about 96% of RNA removed. The higher surface area per
      length of the separation channel in the preparative CPC was believed to benefit
      mass transfer of CTAB across the membrane, leading to less CTAB being required in
      the process.

PMID- 16599575
TI  - Cost-effective recovery and purification of polyhydroxyalkanoates by selective
      dissolution of cell mass.
AB  - Highly efficient separation and purification of polyhydroxyalkanoates (PHAs) from
      PHA-containing cell mass is essential to production of the bioplastics from
      renewable resources in a cost-effective, environmentally friendly way. Based on
      selective dissolution of non-PHA cell mass (NPCM) by protons in aqueous solution
      and crystallization kinetics of PHA biopolymers, a simple process is developed
      and demonstrated to recover PHAs from cell mass to high purity (>97 wt %) with
      high yield (>95 wt %). The average molecular weight of biopolyesters is
      controlled, which follows an exponential function of process severity, a combined
      factor of processing conditions. Compared with conventional chemical treatment
      such as sequential surfactant and hypochlorite treatment, this new technology
      substantially reduces the chemical cost for PHA recovery and purification from
      PHA-containing cell mass.

PMID- 16599574
TI  - Normal phase high-performance liquid chromatography of pneumocandins: in situ
      modification of silica with L-proline to separate structural analogues.
AB  - Lipopeptides such as pneumocandin B(0) are often produced by fermentation
      processes. Many compounds with similar structures (structural analogues), and
      hence similar physiochemical properties, are coproduced in the fermentation. We
      employed high performance liquid chromatography using silica gel as the
      stationary phase and a ternary ethyl acetate/MeOH/water mobile phase to separate
      pneumocandin B(0) from these structural analogues. Despite extensive efforts to
      optimize this system, two key structural analogues, pneumocandin E(0) and
      pneumocandin B(5), continued to be poorly resolved from the main product peak
      (pneumocandin B(0)). As a result, feed load was restricted and productivity was
      limited. In situ modification of the silica gel stationary phase with l-proline
      or other amino acids significantly enhances the resolution of the two key
      structural analogues from the compound of interest, enabling a two-fold increase
      in productivity. Results of a systematic study showed that the amine group in l
      proline and other amino acids plays a key role in the modification of the surface
      of the silica gel to mediate the selectivity enhancement.

PMID- 16599576
TI  - Assembly of human papillomavirus type-16 virus-like particles: multifactorial
      study of assembly and competing aggregation.
AB  - Pentameric capsomeres of human papillomavirus capsid protein L1 expressed in
      Escherichia coli self-assemble into virus-like particles (VLPs) in vitro. A
      multifactorial experimental design was used to explore a wide range of solution
      conditions to optimize the assembly process. The degree of assembly was measured
      using an enzyme-linked immunosorbent assay, and a high-throughput turbidity assay
      was developed to monitor competing aggregation. The presence of zinc ions in the
      assembly buffer greatly increased the incidence of aggregation and had to be
      excluded from the experiment for meaningful analysis. Assembly of VLPs was
      optimal at a pH of about 6.5, calcium and sodium ions had no measurable effect,
      and dithiothreitol and glutathione inhibited assembly. Tryptophan fluorescence
      spectroscopy demonstrated that an increase in urea concentration reduced the rate
      of VLP formation but had no effect on the final concentration of assembled VLPs.
      This study demonstrates the use of the hanging-drop vapor-diffusion
      crystallization method to screen for conditions that promote aggregation and the
      use of tryptophan fluorescence spectroscopy for real-time monitoring of the
      assembly process.

PMID- 16599577
TI  - Production of islet-like structures from neonatal porcine pancreatic tissue in
      suspension bioreactors.
AB  - The aim of this study was to develop a scaleable process to expand pancreatic
      endocrine tissue (i.e., aggregates or islet-like structures) in suspension
      bioreactors. Key issues addressed included (i) serum-free media, (ii) cell
      inoculation density, (iii) medium pH, and (iv) aggregate dissociation. Suspension
      bioreactors were inoculated with pancreatic neonatal tissue and operated under
      controlled conditions for a 9-day period. Medium studies showed that a new serum
      free medium developed in our laboratory was capable of supporting endocrine cell
      expansion. An inoculation density of 127,000 cells/mL resulted in more than a 7.5
      fold increase in the number of insulin-positive cells after 9 days. The resulting
      population consisted of single cells and many islet-like aggregates that
      contained all of the endocrine cell types (including insulin-positive, glucagon
      positive, somatostatin-positive, and pancreatic polypeptide-positive cells).
      Furthermore, the cell aggregates exhibited a glucose-responsive behavior. This
      study represents a significant milestone on the path to the effective expansion
      of human islet-like tissue in bioreactors that may be used for cell therapy to
      treat Type 1 diabetes.

PMID- 16599578
TI  - Screening of novel excipients for improving the stability of retroviral and
      adenoviral vectors.
AB  - In the past decade there has been an increase in the application of viral vectors
      in the laboratory and clinical trials of human gene therapy, retroviral and
      adenoviral vectors among the most used. However, the limited stability of these
      vectors creates problems in the design of experiments, transport, and storage.
      Vectors stored at -80 degrees C must be quickly shipped on dry ice, which is
      somewhat cumbersome. Alternatively, viral vectors can be preserved in a
      lyophilized form. However, loss of viral activity during lyophilization can also
      be a serious problem. In this report we identify novel candidate formulations
      containing new compatible solutes, ectoin, hydroxyectoin, and firoin, that allow
      better stability of retroviral and adenoviral vectors during storage. For
      retroviral vectors, the maximum stabilization for long-term storage was achieved
      through lyophilization followed by storage at -20 degrees C using a formulation
      of Tris buffer pH 7.2 containing firoin (0.5 M), a half-life of 340 days being
      obtained. Adenoviral vectors storage at -80 degrees C in solution using Tris
      buffer pH 8.0 with firoin was the best method for long-term storage, with a half
      life exceeding 1 year.

PMID- 16599579
TI  - Synthesis of gold nanotriangles and silver nanoparticles using Aloe vera plant
      extract.
AB  - Biogenic gold nanotriangles and spherical silver nanoparticles were synthesized
      by a simple procedure using Aloe vera leaf extract as the reducing agent. This
      procedure offers control over the size of the gold nanotriangle and thereby a
      handle to tune their optical properties, particularly the position of the
      longitudinal surface plasmon resonance. The kinetics of gold nanotriangle
      formation was followed by UV-vis-NIR absorption spectroscopy and transmission
      electron microscopy (TEM). The effect of reducing agent concentration in the
      reaction mixture on the yield and size of the gold nanotriangles was studied
      using transmission electron microscopy. Monitoring the formation of gold
      nanotriangles as a function of time using TEM reveals that multiply twinned
      particles (MTPs) play an important role in the formation of gold nanotriangles.
      It is observed that the slow rate of the reaction along with the shape directing
      effect of the constituents of the extract are responsible for the formation of
      single crystalline gold nanotriangles. Reduction of silver ions by Aloe vera
      extract however, led to the formation of spherical silver nanoparticles of 15.2
      nm +/- 4.2 nm size.

PMID- 16599580
TI  - One-step, painting-like coating procedures to make surfaces highly and
      permanently bactericidal.
AB  - Previously we found that covalent attachment of long-chained, moderately
      hydrophobic polycations to surfaces of solid objects renders the latter
      permanently bactericidal. Herein we replaced such surface-specific, multistep
      immobilization techniques with a single-step, general procedure akin to common
      painting. Glass or polyethylene slides were briefly dipped into organic solutions
      of certain optimally hydrophobic N-alkyl-PEI (where PEI stands for branched 750
      kDa polyethylenimine) polycations, followed by solvent evaporation. The resultant
      polycation-coated slides were able to kill on contact all of the encountered
      bacterial cells, whether the Gram-positive human pathogen Staphylococcus aureus
      or its Gram-negative brethren Escherichia coli. This biocidal effect was found
      not to be caused by N-alkyl-PEI molecules leached from the surface. Further
      examination of the mechanism of this bactericidal action suggested that the
      surface-deposited N-alkyl-PEI kills bacteria by rupturing their cellular
      membranes. This conclusion was further supported by studies in which the
      molecular weight of PEI and the hydrophobicity of the alkyl moiety were varied.

PMID- 16599581
TI  - Simple purification of immunoglobulins from whey proteins concentrate.
AB  - We have developed a new protocol with only two steps for purification of
      immunoglobulins (Ig) from a protein concentrate of whey. Following this protocol,
      we have an 80% recovery of immunoglobulins, fairly pure. The purification was
      achieved by eliminating the BSA, via a strong adsorption on DEAE-agarose. Full
      desoprtion of the other serum proteins could be achieved without contamination
      with BSA. Thus, a protein solution containing only Ig and very small proteins
      (e.g., beta-lactoglobulins and alpha-lactalbumin) was obtained. Offering this
      protein mixture to a lowly activated aminated support, only Ig adsorbed on the
      support. It has been shown that BSA is able to interact with other proteins
      (including Ig and lactalbumins). This ability to form complexes with other
      proteins prevented the success of the direct adsorption of Ig on this mildly
      activated support, even although Ig should be the largest protein presented in
      dairy whey.

PMID- 16599582
TI  - Application of fractional factorial designs to screen active factors for antibody
      production by chinese hamster ovary cells.
AB  - With ever increasing need for cost-effective large-scale production of monoclonal
      antibodies, it is essential to develop highly productive and commercially viable
      processes. Previous research showed that growth and production capacity of the
      culture media can be improved by micronutrient supplements, such as insulin,
      vitamins, and growth factors. Since these micronutrients may not act
      independently of one another, factorial designs can expose critical interactions
      between nutrients as opposed to a serial approach of changing one factor at a
      time. In this study, fractional factorial designs were applied to observe the
      effect of several micronutrients on antibody production and culture longevity in
      shake flasks. Response surface designs were used to investigate the factors in
      depth and confirm the results of the fractional factorial study. The results
      demonstrate that fractional factorial design is an effective tool for rapid
      development of antibody-producing Chinese hamster ovary (CHO) cells.

PMID- 16599583
TI  - An improved phage display procedure for identification of lipopolysaccharide
      binding peptides.
AB  - We successfully implemented several modifications to the regular phage display
      procedure and significantly improved the lipopolysaccharides-binding properties
      of the peptides selected. Specifically, the number of biopannings was increased
      and peptides with consensus sequences were obtained. A dual selection procedure
      (referred to as subtractive panning) was used to simultaneously select for the
      desired target and deselect for an undesired target, thereby increasing the
      binding specificity. In addition, binding and washing conditions in the
      subtractive panning were also modified to favor the selection of peptides with
      higher binding strength. As a result, two peptides, ASFPPAF and SSHTISF, were
      identified with much improved binding properties compared to those selected with
      regular panning. The binding specificities of these two peptides, as measured by
      the ratio of phages bound to the desired and undesired targets, were severalfold
      higher than previously reported. These modifications could easily be implemented
      with many other target molecules, indicating the general applicability of the
      procedure.

PMID- 16599584
TI  - Predicting solvent and aggregation effects of peptides using group contribution
      calculations.
AB  - Assembly of proteins and peptides into amyloid fibrils is characteristic of the
      pathology of a number of degenerative diseases, of which perhaps the best known
      is Alzheimer's. Neuronal death in Alzheimer's disease has been linked to
      aggregation of beta-amyloid peptide and deposition of the aggregates in brain
      tissue. Recent studies suggest that soluble intermediate oligomers rather than
      fully formed fibrils may be responsible for beta-amyloid's toxicity; consistent
      with this hypothesis, some compounds that inhibited beta-amyloid toxicity were
      found to accelerate aggregation of the peptide. The degree of increase of
      aggregation caused by these compounds was shown to correlate strongly with their
      effect on the surface tension of aqueous buffers (Gibson, T. J.; Murphy, R. M.
      Biochemistry 2005, 44, 8898-8907). In work reported here, we used group
      contribution methods to calculate infinite dilution activity coefficients of
      moieties contained in these compounds. We demonstrate that activity coefficients
      calculated in this manner are strongly predictive of effects of these peptides on
      solvent surface tension and on beta-amyloid aggregation. These results suggest
      that group contribution calculations can be used for a priori design of compounds
      that modulate aggregation of peptides through their effect on solvent properties.

PMID- 16599585
TI  - Synthesis and conformational analysis of bicyclic sulfonium salts. Structures
      related to the glycosidase inhibitor australine.
AB  - The syntheses of eight sulfonium compounds with structures related to the
      naturally occurring pyrrolizidine alkaloid, australine, in which the bridgehead
      nitrogen atom is replaced by a sulfonium ion, are described. The synthetic
      strategy relies on the intramolecular attack of a cyclic thioether across a
      terminal double bond in the presence of a suitable electrophile. We postulate
      that these compounds, having a permanent positive charge on the sulfur atom, will
      mimic the highly unstable oxacarbenium ion transition state in a glycosidase
      catalyzed hydrolysis reaction. The conformational preferences of these compounds,
      based on analysis of 1H-1H vicinal coupling constants and 1D-NOESY data, are
      attributed to both steric and electrostatic interactions. These compounds will be
      used in the study of structure-activity relationships with glycosidase enzymes.

PMID- 16599586
TI  - Molecular recognition: improved binding of biotin derivatives with synthetic
      receptors.
AB  - NMR titrations and Monte Carlo conformational searches have been used to study
      the molecular recognition features of five urea derivatives with two synthetic
      hosts. We have improved the binding constant (Kb) values for all the studied
      guests and measured the largest binding constant of a complex involving a biotin
      derivative (biotin methyl ester) bound to a synthetic host by means of several
      interaction points and not only through the urea moiety.

PMID- 16599587
TI  - Molecular structure and conformations of benzenesulfonamide: gas electron
      diffraction and quantum chemical calculations.
AB  - The molecular structure and conformational properties of benzenesulfonamide,
      C6H5SO2NH2, were studied by gas electron diffraction (GED) and quantum chemical
      methods (MP2 and B3LYP with different basis sets). The calculations predict the
      presence of two stable conformers with the NH2 group eclipsing or staggering the
      SO2 group. The eclipsed form is predicted to be favored by about 0.5 kcal/mol.
      According to GED, the saturated vapor over solid benzenesulfonamide at a
      temperature of 150(5) degrees C consists of the eclipsed conformer. The GED
      intensities, however, possess a very low sensitivity toward the vapor
      composition, and contributions of the anti conformer of up to 75% (at the 0.05
      level of significance) or up to 55% (at the 0.25 level of significance) cannot be
      excluded. The molecule possesses C(sS) symmetry with the S-N bond perpendicular
      to the ring plane.

PMID- 16599588
TI  - Carboxylate-based receptors for the recognition of carbohydrates in organic and
      aqueous media.
AB  - Acyclic receptors containing neutral and ionic hydrogen-bonding sites, such as
      amino-pyridine and carboxylate groups, were prepared and their binding properties
      toward neutral sugar molecules were studied. The binding studies with disodium
      and bis(tetramethylammonium) salts containing the dianion 11 have revealed that
      this type of receptor molecule is able to recognize the selected sugars in both
      organic and aqueous media. The carboxylate/pyridine-based receptor 11 exhibits in
      chloroform at least a 100-fold higher affinity for glucopyranosides than the
      previously described triarmed pyridine-based receptor 1, incorporating only
      neutral hydrogen-bonding sites. A substantial drop in the association constants
      is expectedly observed for an ester analogue of 11, compound 9. The dicarboxylate
      11 is able to form complexes in water with methyl beta-D-glucopyranoside and D
      cellobiose, with a preference for the disaccharide. The studies show the
      importance of charge-reinforced hydrogen bonds in the recognition of
      carbohydrates.

PMID- 16599590
TI  - Cyclic oligothiophenes: novel organic materials and models for polythiophene. A
      theoretical study.
AB  - Cyclic oligothiophenes (CnT, n = 6-30, even only) in syn- and anti-conformations
      are studied theoretically at the B3LYP/6-31G(d) level of theory. Strain energies,
      ionization potentials, HOMO-LUMO gaps, bond length alternations, NICS values, and
      IR and Raman spectra have been studied. The properties of anti-conformers change
      systematically with increasing ring size and were studied in detail in neutral,
      radical cation, and dication forms. In syn-conformation, the oligomers lose their
      nearly planar ring shape and bend significantly for n > 14, and thus properties
      cannot be related to ring size. The HOMO-LUMO gap in C14T-syn is even lower than
      polythiopehene. IR and Raman spectra calculated at the B3LYP/6-31G(d) level are
      used to differentiate syn- from anti-conformations. The properties of cyclic
      oligomers are compared to those of the linear system, and cyclic oligothiophenes
      are revealed as good models for polythiophene. To assist the experimental study
      of known cyclic oligomers having dibutyl substituents on alternate thiophene
      rings, the corresponding dimethyl-substituted oligomers are also studied. The
      experimentally evaluated HOMO-LUMO gaps for alternately dibutyl-substituted
      cyclic oligomers match the calculated values; however, they are significantly
      higher than those of the unsubstituted analogues.

PMID- 16599589
TI  - 15N NMR chemical shifts for the identification of dipyrrolic structures.
AB  - A variety of dipyrromethanes and dipyrromethenes have been prepared, and their
      15N NMR chemical shifts have been measured by two-dimensional correlation to 1H
      NMR signals. The nitrogen atoms in five examples of dipyrromethanes consistently
      exhibit chemical shifts around -231 ppm, relative to nitromethane. Seven examples
      of hydrobromide salts of meso-unsubstituted dipyrromethenes consistently display
      15N chemical shifts around -210 ppm, while their corresponding zinc(II) complexes
      exhibit chemical shifts around -170 ppm. The presence of electron-withdrawing
      substituents on one of the pyrrolic rings of dipyrromethenes affects the chemical
      shifts of both of the nitrogen nuclei in the molecule. Boron difluoride complexes
      of meso-unsubstituted dipyrromethenes display 15N chemical shifts around -190
      ppm. Two examples of free-base dipyrromethenes bearing substituents at the meso
      position exhibit 15N chemical shifts at approximately -156 ppm, and for the zinc
      complexes of these compounds at -162 ppm. One-bond nitrogen-hydrogen coupling
      constants, when measurable, were consistently in the range of -96 Hz. Since the
      measured 15N chemical shifts have such a high regularity correlated to structure,
      they can be used as diagnostic indications for identifying the structure of
      dipyrrolic compounds.

PMID- 16599591
TI  - Cooperative and competitive effects of substituents at C1 and C4 on the barriers
      to ring inversion of 5,5-difluorobicyclo[2.1.0]pentanes.
AB  - To identify the reasons for the very low barrier that has been measured for ring
      inversion of 1,4,5,5-tetrafluorobicyclo[2.1.0]pentane (deltaG(double dagger) =
      6.8 +/- 0.2 kcal/mol), CASSCF and CASPT2 calculations have been performed on ring
      inversion in this and other bicyclo[2.1.0]pentanes. The results of the
      calculations show that a cooperative interaction between the geminal fluorines at
      C2 and the fluorines at C1 and C3 in the singlet cyclopentane-1,3-diyl transition
      structure (TS) contributes 3.7 kcal/mol to lowering the barrier to ring inversion
      in the tetrafluoro compound. In contrast, a competitive substituent effect in the
      TS for ring inversion of 1,4-dicyano-5,5-difluorobicyclo[2.1.0]pentane is
      predicted to raise the barrier height by 6.1 kcal/mol. The origin of these
      cooperative and competitive substituent effects is discussed.

PMID- 16599592
TI  - Synthesis of multi(metallo)porphyrin dendrimers through nucleophilic aromatic
      substitution on meso-pyrimidinyl substituted porphyrins.
AB  - A convergent synthetic strategy toward novel all-porphyrin dendrimers, which can
      be regarded as synthetic model systems of the natural photosynthetic light
      harvesting antennae, was successfully explored. The dendron propagation, based on
      nucleophilic aromatic substitution reactions on a meso-dichloropyrimidinyl
      substituted porphyrin AB2 monomer, was carried out up to the second-generation
      dendron, and the used approach was proven to be compatible with the stepwise
      introduction of different metals in the successive generations. Three different
      metals (Pt, Zn, and Ni) could be introduced in the second-generation
      heptaporphyrin dendron. By applying analogous meso-dichloropyrimidinyl
      substituted porphyrin cores, novel multiporphyrin dendrimers were obtained.

PMID- 16599593
TI  - Kinetic substituent and solvent effects in 1,3-dipolar cycloaddition of
      diphenyldiazomethanes with fullerenes C60 and C70: a comparison with the addition
      to TCNE, DDQ, and chloranil.
AB  - Kinetics of 1,3-dipolar cycloaddition of a series of meta- and para-substituted
      diphenyldiazomethanes (DDMs) with fullerenes C60 and C70 as dipolarophiles have
      been investigated in toluene at 30 degrees C. Fullerene C60 was ca. 1.5 times
      more reactive than C70. The rate constants (k) for the primary [3 + 2] additions
      increased with the increase of the electron-releasing ability of the meta and
      para substituent. The log k/k0 values were well correlated by the Yukawa-Tsuno (Y
      T) equations with the smaller negative rho values (-1.6 and -1.7 for C60 and C70)
      and the reduced resonance reaction constants r (0.22 and 0.17) compared to
      similar reactions of common acceptors, TCNE, DDQ, and chloranil (CA). The plots
      of log k (acceptor) versus log k (C60) as reference gave good regression
      equations and the slopes became larger in the order of TCNE > DDQ > CA > C70 > or
      = C60. The rates were also found to decrease with the increase of solvent
      polarity due to the ground-state solvation of fullerenes. However, the relative
      reactivity of these acceptors toward the unsubstituted DDM increased in the order
      of DDQ > C60 > or = C70 > TCNE > CA. The unexpected higher reactivity of
      fullerenes was interpreted in terms of the inherent steric strain by the
      pyramidalization of the sp2 C-atoms as well as the shorter [6,6] bonds with
      larger pi-electron densities.

PMID- 16599594
TI  - [10]Annulene: bond shifting and conformational mechanisms for automerization.
AB  - We report density-functional and coupled-cluster calculations on conformation
      change and degenerate bond shifting in [10]annulene isomers 1-5. At the
      CCSD(T)/cc-pVDZ//CCSD/6-31G level, conversion of the twist (1) to the heart (2)
      has a barrier of 10.1 kcal/mol, compared to Ea = 16.2 kcal/mol for degenerate
      "two-twist" bond shifting in 1. Pseudorotation in the all-cis boat isomer (3)
      proceeds with a negligible barrier. The naphthalene-like isomer 4 has a 3.9
      kcal/mol barrier to degenerate bond shifting. The azulene-like isomer 5 is the
      only species for which the nature of the bond-equalized form (5-eq) depends on
      the method. At the CCSD(T)/cc-pVDZ//CCSD/6-31G level, 5-eq is 1.2 kcal/mol more
      stable than the bond-alternating form 5-alt. Conversion of 5-eq to 4 has a
      barrier of 12.6 kcal/mol. Despite being significantly nonplanar, both 5-eq and
      the transition state for bond shifting in 4 are highly aromatic based on magnetic
      susceptibility exaltations. On the basis of a detailed consideration of these
      mechanisms and barriers, we can now, with greater confidence, rule out 4 and 5 as
      candidates to explain the NMR spectra observed by Masamune. Our results support
      Masamune's original assignments for both isolated isomers.

PMID- 16599595
TI  - A new class of glucosidase inhibitor: analogues of the naturally occurring
      glucosidase inhibitor salacinol with different ring heteroatom substituents and
      acyclic chain extension.
AB  - Six chain-extended analogues of the naturally occurring glycosidase inhibitor
      salacinol, with ring-heteroatom variation, were synthesized for structure
      activity studies with different glycosidase enzymes. The syntheses involved the
      reaction of PMB-protected D- and L- seleno-, thio-, and iminoarabinitol with a
      benzylidene- and isopropylidene-protected 1,3-cyclic sulfate, derived from
      commercially available D-sorbitol, in 1,1,1,3,3,3-hexafluoro-2-propanol
      containing potassium carbonate. Deprotection of the products afforded the novel
      selenonium, sulfonium, and iminium analogues of salacinol containing
      polyhydroxylated, monosulfated, extended acyclic chains of 6-carbons, differing
      in stereochemistry at the stereogenic centers and ring-heteroatom constitution.
      Four of these compounds inhibit recombinant human maltase glucoamylase, one of
      the key intestinal enzymes involved in the breakdown of glucose oligosaccharides
      in the small intestine, with Ki values in the micromolar range, thus providing
      lead candidates for the treatment of Type 2 diabetes.

PMID- 16599596
TI  - Cycloaddition between electron-deficient pi-systems, photochemical and radical
      induced reactions: a novel, general, and stereoselective route to
      polyfunctionalized bridged bicyclo[2.2.2]octanes, bicyclo[3.3.0]octanes,
      bicyclo[4.2.0]octanes, and tricyclo[4.3.1.0(3,7)]decanes.
AB  - A novel, general, and stereoselective route to functionalized bridged
      bicyclo[2.2.2]octanes, bicyclo[3.3.0]octanes, bicyclo[4.2.0]octanes, and
      tricyclo[4.3.1.0(3,7)]decanes has been described. Various functionalized and
      substituted bicyclo[2.2.2]octanes endowed with a beta,gamma-enone chromophore
      were synthesized via cycloaddition of in situ generated cyclohexa-2,4-dienones
      with electron-deficient 2pi partners and manipulation of the resulting adducts.
      Triplet sensitized irradiation of bridged bicyclooctenones led to synthesis of
      bicyclo[3.3.0]octanoids, whereas the direct irradiation furnished
      bicyclo[4.2.0]octanes in stereoselective fashion as a result of modulation of
      reactivity in excited states. Further, manipulation of the adducts led to
      appropriately appended and functionalized bicyclo[2.2.2]octanes that upon radical
      induced cyclization provided an efficient and stereoselective route to the
      tricyclo[4.3.1.0(3,7)]decane (isotwistane) framework of pupukeananes.

PMID- 16599597
TI  - New easy approach to the synthesis of 2,5-disubstituted and 2,4,5-trisubstituted
      1,3-oxazoles. The reaction of 1-(methylthio)acetone with nitriles.
AB  - The reaction of 1-(methylthio)acetone with different nitriles in the presence of
      triflic anhydride led to the one-pot formation of 2-substituted 5-methyl-4
      methylthio-1,3-oxazoles in good yield. 1,2- and 1,4-Bisozaxolyl-substituted
      benzenes were obtained when the reaction was carried out using aromatic
      dinitriles. The methylthio group at the C4 position of the oxazole ring was
      easily removed with Raney nickel to form 2-substituted 5-methyl-1,3-oxazoles in
      good yields. 4-Methylsulfonyl derivatives were prepared by the oxidation of the
      MeS group with m-CPBA. The proposed mechanism for the formation of oxazoles
      involves an unstable 1-(methylthio)-2-oxopropyl triflate, which was detected from
      the low-temperature NMR spectra.

PMID- 16599598
TI  - Investigation of stepwise covalent synthesis on a surface yielding porphyrin
      based multicomponent architectures.
AB  - Porphyrins have been shown to be a viable medium for use in molecular-based
      information storage applications. The success of this application requires the
      construction of a stack of components ("electroactive surface/tether/charge
      storage molecule/linker/electrolyte/top contact") that can withstand high
      temperature conditions during fabrication (up to 400 degrees C) and operation (up
      to 140 degrees C). To identify suitable chemistry that enables in situ stepwise
      synthesis of covalently linked architectures on an electroactive surface, three
      sets of zinc porphyrins (22 altogether) have been prepared. In the set designed
      to form the base layer on a surface, each porphyrin incorporates a surface
      attachment group (triallyl tripod or vinyl monopod) and a distal functional group
      (e.g., pentafluorophenyl, amine, bromo, carboxy) for elaboration after surface
      attachment. A second set designed for in situ dyad construction incorporates a
      single functional group (alcohol, isothiocyanato) that is complementary to the
      functional group in the base porphyrins. A third set designed for in situ multad
      construction incorporates two identical functional groups (bromo, alcohol, active
      methylene, amine, isothiocyanato) in a trans configuration (5,15-positions in the
      porphyrin). Each porphyrin that bears a surface attachment group was found to
      form a good quality monolayer on Si(100) as evidenced by the voltammetric and
      vibrational signatures. One particularly successful chemistry identified for
      stepwise growth entailed reaction of a surface-tethered porphyrin-amine with a
      dianhydride (e.g., 3,3',4,4'-biphenyltetracarboxylic dianhydride), forming the
      monoimide/monoanhydride. Subsequent reaction with a diamine (e.g., 4,4'-methylene
      bis(2,6-dimethylaniline)) gave the bis(imide) bearing a terminal amine.
      Repetition of this stepwise growth process afforded surface-bound oligo-imide
      architectures composed of alternating components without any reliance on
      protecting groups. Taken together, the ability to prepare covalently linked
      constructs on a surface without protecting groups in a stepwise manner augurs
      well for the systematic preparation of a wide variety of functional molecular
      devices.

PMID- 16599599
TI  - Construction of highly glycosylated mucin-type glycopeptides based on microwave
      assisted solid-phase syntheses and enzymatic modifications.
AB  - A MUC1-related glycopeptide having five core-2 hexasaccharide branches
      (C330H527N46O207, MW = 8450.9) was synthesized by a new strategy using a
      combination of microwave-assisted solid-phase synthesis (MA-SPGS) and enzymatic
      sugar elongation. Synthesis of a key glycopeptide intermediate was best achieved
      in a combination of PEGA [poly(ethylene glycol)-poly-(N,N-dimethylacrylamide)
      copolymer] resin and MA-SPGS using glycosylated amino acid building blocks with
      high speed and high purity. Deprotection of the glycopeptide intermediate and
      subsequent glycosyltransferase-catalyzed sugar elongations were performed for
      generation of the additional diversities with the sugar moieties of glycopeptides
      using beta1,4-galactosyltransferase (beta1,4-GalT) and two kinds of alpha2,3
      sialyltransferases [ST3Gal III; alpha2,3-(N)-SiaT and ST3Gal II; alpha2,3-(O)
      SiaT]. These reactions proceeded successfully in the presence of 0.2% Triton X
      100 to convert the chemically synthesized trisaccharide glycans to disialylated
      hexasaccharide.

PMID- 16599601
TI  - Acid-catalyzed cyclization of anthracenol derivatives to homotriptycenes.
AB  - 10-Benzyl-9,10-dihydroanthracen-9-ols, having high electron densities in the
      benzene ring, exhibit in the presence of acid a transannular ring closure to the
      corresponding homotriptycenes in almost quantitative yields. Since the starting
      compounds are easily accessible from 9(10H)-anthracenone, this process represents
      the most facile route to such pentacyclic systems. An electron-releasing methoxy
      group enables the intramolecular electrophilic substitution in its para position.
      In the absence of such an activation, a number of alternative processes can
      occur, namely the acid-catalyzed dehydration to anthracene derivatives with (R
      not = H) or without (R = H) rearrangement or a disproportionation reaction of the
      secondary alcohol to the corresponding ketone and hydrocarbon.

PMID- 16599600
TI  - Enhanced diastereoselectivity in beta-mannopyranosylation through the use of
      sterically minimal propargyl ether protecting groups.
AB  - [reaction: see text] 2-O-Propargyl ethers are shown to be advantageous in the 4,6
      O-benzylidene acetal directed beta-mannosylation reaction. The effect is most
      pronounced when the O3 protecting group is a bulky silyl ether or a glycosidic
      bond; however, even with a 3-O-benzyl ether, the use of a 2-O-propargyl ether
      results in a significant increase in diastereoselectivity. The beneficial effect
      of the propargyl ether is thought to be a combination of its minimal steric bulk,
      as determined by a measurement of the steric A-value and of its moderately
      disarming nature, as reflected in the pKa of propargyl alcohol. Conversely, the
      application of a 3-O-propargyl ether in the benzylidene acetal directed
      mannosylation has a detrimental effect on stereoselectivity, for which no
      explanation is at present available. Deprotection is achieved by base-catalyzed
      isomerization of the propargyl ether group to the corresponding allenyl ether,
      followed by oxidative cleavage with N-methylmorpholine N-oxide and catalytic
      osmium tetroxide.

PMID- 16599602
TI  - Selective removal of the 2'- and 3'-O-acyl groups from 2',3',5'-tri-O
      acylribonucleoside derivatives with lithium trifluoroethoxide.
AB  - Selective cleavage of O2' and O3' ester groups from ribonucleoside derivatives
      has been accomplished with Dowex 1 x 2 (CF3CH2O-) in 2,2,2-trifluoroethanol (TFE)
      or lithium trifluoroethoxide/TFE. Deacylations with Li+ -OCH2CF3/TFE proceed at
      ambient temperature (or with mild heating) to give the 5'-O-acyl derivatives in
      superior yields and higher purity than prior approaches for selective O2' and O3'
      ester deprotection.

PMID- 16599603
TI  - S(N)/S(N)' competition: selective access to new 10-fluoro artemisinins.
AB  - In this paper, we report a simple route to accede to a new family of C-10
      fluorinated derivatives of artemisinin 7. We demonstrated that nucleophilic
      substitution of the allylic bromide 6 with alcohols can occur at carbon 10
      (compounds 7) under solvolytic conditions (S(N)'/S(N) ratio, 87:13). Furthermore,
      using the particular properties of hexafluoroisopropanol (HFIP), we are able to
      increase the selectivity of the substitution. Primary alcohols are completely
      selective for allylic substitution. With amines as nucleophiles, selectivity of
      substitution is dependent on their nucleophilicity, but attack at carbon 16 was
      always favored. However, the S(N)'/S(N) ratio could be slightly increased by
      adding HFIP, which is able to modulate their nucleophilicity through hydrogen
      bonding. In preliminary in vitro assessments, these new compounds, 7, exhibited a
      satisfying activity against malaria.

PMID- 16599604
TI  - Practical asymmetric synthesis of a gamma-secretase inhibitor exploiting
      substrate-controlled intramolecular nitrile oxide-olefin cycloaddition.
AB  - A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is
      described. As the key transformation, a highly diastereoselective intramolecular
      nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four
      operations. Other aspects of the route include a highly stereoselective reduction
      of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical
      resolution, a dianion cyclization to construct a sultam ring, and the alpha
      alkylation of a sultam with excellent diastereoselectivity. In each instance, the
      relative stereochemistry was evolved by way of substrate-based induction with >
      or = 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were
      obtained, without recourse to chromatography, by way of 10 isolated intermediates
      and in 13% overall yield.

PMID- 16599605
TI  - Isocyanate-, isothiocyanate-, urea-, and thiourea-substituted boron
      dipyrromethene dyes as fluorescent probes.
AB  - Boron dipyrromethene dyes (Bodipy) bearing a meso-phenyl substituent carrying a
      variety of functional groups can be prepared under mild conditions. A single
      crystal X-ray structure determination for the 3,5-dinitrophenyl compound shows
      the phenyl ring to be almost orthogonal (dihedral angle 84 degrees) to the plane
      of the Bodipy core, with one nitro group almost coplanar with the ring and the
      other tilted by approximately 21 degrees. Nitro substituents at the 3-, 4-, and 5
      positions of the phenyl group are readily reduced to the corresponding amino
      groups and then converted to isocyanato, isothiocyanato, urea, thiourea, and some
      polyimine derivatives, the last providing additional functionality (phenazine and
      pyridylindole units) suitable for chelation of metal ions. All compounds are
      redox active, the electron-transfer processes being assigned on the basis of
      comparisons with model compounds. Their fluorescence properties are sensitive to
      the phenyl group substituents. The Bodipy unit excited state appears to be a
      strong reductant (Eo approximately -1.4 V) and a modest oxidant (Eo approximately
      +1.0 V). Quenching processes in the nitro and phenazine derivatives appear to
      involve intramolecular photoinduced electron transfer.

PMID- 16599606
TI  - Accuracy vs time dilemma on the prediction of NMR chemical shifts: a case study
      (chloropyrimidines).
AB  - The nuclear magnetic shieldings of two chloropyrimidine species have been
      predicted and analyzed by means of ab initio and DFT methods. The results have
      been compared with the experimental values and with those from other database
      related approaches. These dataset-based techniques are found to be particularly
      valuable because of the accurate and instantaneous prediction of the 13C chemical
      shifts. On the other hand, only a few quantum chemistry based approaches were
      showed to be the most precise to predict 1H chemical shifts and to elucidate
      unequivocally the 1H NMR spectra of the regioisomeric mixture under study.
      Special emphasis was put on incorporating the solvent effect, implicitly, or
      explicitly. The influence of the level of theory and basis set in the predicted
      values has also been discussed.

PMID- 16599607
TI  - Acylation of nickel meso-tetraarylporphyrins: porphyrin to corrole ring
      contraction and formation of seco-porphyrins.
AB  - Friedel-Crafts acylation of nickel meso-tetraarylporphyrins with aryl anhydrides,
      followed by air oxidation in the presence of pyridine, DMAP, and excess
      anhydride, produced corroles in 8-21% yields. Other products include a
      porphyrinic ketone, an additional corrole whose bridge has been retained as an
      acyl group attached to a pyrrole, and a lactone resulting from the insertion of
      an oxygen atom into an alpha,beta-pyrrole bond. The ring contraction is best
      explained by a pinacolic rearrangement reminiscent of the one taking place in the
      formation of corrinoids, a benzoyloxy group replacing the acetic side chain found
      in the natural products.

PMID- 16599608
TI  - Rational design of new polymerizable oxyanion receptors.
AB  - We report the synthesis of a library of new polymerizable functional monomers
      designed for complexing with the oxyanionic moiety of the chemotherapeutic drug
      methotrexate. The 1H NMR and ITC binding studies allowed for the selection of
      receptors possessing the best association parameters. Subsequently, the design of
      a broad library of polymerizable moiety-specific binding monomers for the
      imprinting of dicarboxylate containing drugs was accomplished.
      Di(ureidoehylenemethacrylate)stilbene possesses the highest association
      properties and shows potential to act as a monomer in the molecularly imprinting
      technique to obtain photoswitchable cavities.

PMID- 16599609
TI  - Pressure and temperature-controlled enantiodifferentiating [4+4]
      photocyclodimerization of 2-anthracenecarboxylate mediated by secondary face- and
      skeleton-modified gamma-cyclodextrins.
AB  - A series of secondary-face-substituted and skeleton-modified gamma-cyclodextrins
      (gamma-CDs) were prepared as chiral hosts for enantiodifferentiating [4+4]
      photocyclodimerization reactions of 2-anthracenecarboxylic acid (AC). These gamma
      CD derivatives form stable ternary complexes with ACs, with altroside-bearing
      gamma-CDs undergoing induced-fit conformational changes upon complexation, and
      the photocyclodimerization of AC was, thus, dramatically accelerated. The
      enantiomeric excess (ee) of anti-head-to-head cyclodimer 3 was greatly enhanced
      in general with altroside-bearing gamma-CDs 7-9. Although mono-altro-gamma-CD 9
      and 3A-azido-3A-deoxy-altro-gamma-CD 7 gave 2 in ee's smaller than those obtained
      with native gamma-CD, 3A-amino-3A-deoxy-altro-gamma-CD 8 yielded 2 in much higher
      ee's, which is likely to be ascribed to the combined effects of the less
      symmetric cavity and the electrostatic interactions. The influence of temperature
      and high pressure on the supramolecular photochirogenic reaction has been
      investigated in depth. An ee as high as 71% was obtained for cyclodimer 2 in the
      photocyclodimerization of AC mediated by 8 at 210 MPa and -21.5 degrees C.

PMID- 16599610
TI  - Novel and expeditious microwave-assisted three-component reactions for the
      synthesis of spiroimidazolin-4-ones.
AB  - Highly efficient methods for the syntheses of spiroimidazolinones via microwave
      assisted three-component one-pot sequential reactions or one-pot domino reactions
      are described. The efficiency and utility of the methods have been demonstrated
      by quickly accessing the antihypertensive drug irbesartan (2).

PMID- 16599611
TI  - Substituent cross-interaction effects on the electronic character of the C=N
      bridging group in substituted benzylidene anilines--models for molecular cores of
      mesogenic compounds. A 13C NMR study and comparison with theoretical results.
AB  - 13C NMR chemical shifts delta(C)(C=N) were measured in CDCl3 for a wide set of
      mesogenic molecule model compounds, viz. the substituted benzylidene anilines p-X
      C6H4CH=NC6H4-p-Y (X = NO2, CN, CF3, F, Cl, H, Me, MeO, or NMe2; Y = NO2, CN, F,
      Cl, H, Me, MeO, or NMe2). The substituent dependence of delta(C)(C=N) was used as
      a tool to study electronic substituent effects on the azomethine unit. The
      benzylidene substituents X have a reverse effect on delta(C)(C=N): electron
      withdrawing substituents cause shielding, while electron-donating ones behave
      oppositely, the inductive effects clearly predominating over the resonance
      effects. In contrast, the aniline substituents Y exert normal effects: electron
      withdrawing substituents cause deshielding, while electron-donating ones cause
      shielding of the C=N carbon, the strengths of the inductive and resonance effects
      being closely similar. Additionally, the presence of a specific cross-interaction
      between X and Y could be verified. The electronic effects of the neighboring
      aromatic ring substituents systematically modify the sensitivity of the C=N group
      to the electronic effects of the benzylidene or aniline ring substituents.
      Electron-withdrawing substituents on the aniline ring decrease the sensitivity of
      delta(C)(C=N) to the substitution on the benzylidine ring, while electron
      donating substituents have the opposite effect. In contrast, electron-withdrawing
      substituents on the benzylidene ring increase the sensitivity of delta(C)(C=N) to
      the substituent on the aniline ring, while electron-donating substituents act in
      the opposite way. These results can be rationalized in terms of the substituent
      sensitive balance of the electron delocalization (mesomeric effects). The present
      NMR characteristics are discussed as regards the computational literature data.
      Valuable information has been obtained on the effects of the substituents on the
      molecular core of the mesogenic model compounds.

PMID- 16599612
TI  - Cannizzaro-type disproportionation of aromatic aldehydes to amides and alcohols
      by using either a stoichiometric amount or a catalytic amount of lanthanide
      compounds.
AB  - Aromatic aldehydes can be directly converted to the corresponding amides and
      alcohols in good to excellent yields by the treatment of aromatic aldehydes with
      lithium amide LiN(SiMe3)2 in the presence of catalytic lanthanide chlorides LnCl3
      or by the treatment of aromatic aldehydes with a stoichiometric amount of
      lanthanide amides [(Me3Si)2N]3Ln(mu-Cl)Li(THF)3 at ambient temperature. The
      effects of solvents, substitutents on the phenyl ring, and lanthanide metals on
      the reaction have been examined. The mechanism of the disproportionation reaction
      was proposed based on the experimental results.

PMID- 16599613
TI  - Preparation of partially substituted 1-halo- and 1,4-dihalo-1,3-dienes via
      reagent-controlled desilylation of halogenated 1,3-dienes.
AB  - Depending on the desilylation reagents used, 1-halo-1,4-bis(trimethylsilyl)-1,3
      butadienes afforded either 1-halo-1-trimethylsilyl-1,3-butadienes or 1-halo-4
      trimethylsilyl-1,3-butadienes in excellent yields with excellent selectivity,
      respectively, when treated with CF3COOH or with NaOMe. These monosilylated 1,3
      butadiene products could be further desilylated to generate their corresponding
      halobutadienes via the above reagent-controlled desilylation reaction. When 1,4
      dihalo-1,4-bis(trimethylsilyl)-1,3-dienes were treated with MeONa/MeOH at room
      temperature, desilylation of both of the two trimethylsilyl groups took place to
      afford their corresponding 1,4-dihalo-1,3-dienes in excellent yields. The
      commonly used desilylation reagent CF3COOH did not work for these
      dihalobutadienes.

PMID- 16599615
TI  - Oxygen acidity of ring methoxylated 1,1-diarylalkanol radical cations bearing
      alpha-cyclopropyl groups. The competition between O-neophyl shift and C
      cyclopropyl beta-scission in the intermediate 1,1-diarylalkoxyl radicals.
AB  - A product and time-resolved kinetic study on the reactivity of the radical
      cations generated from cyclopropyl(4-methoxyphenyl)phenylmethanol (1) and
      cyclopropyl[bis(4-methoxyphenyl)]methanol (2) has been carried out in aqueous
      solution. In acidic solution, 1*+ and 2*+ display very low reactivities toward
      fragmentation, consistent with the presence of groups at Calpha (aryl and
      cyclopropyl) that after Calpha-Cbeta bond cleavage would produce relatively
      unstable carbon-centered radicals. In basic solution, 1*+ and 2*+ display oxygen
      acidity, undergoing -OH-induced deprotonation from the alpha-OH group, leading to
      the corresponding 1,1-diarylalkoxyl radicals 1r* and 2r*, respectively, as
      directly observed by time-resolved spectroscopy. The product distributions
      observed in the reactions of 1*+ and 2*+ under these conditions (cyclopropyl
      phenyl ketone, cyclopropyl(4-methoxyphenyl) ketone, and 4-methoxybenzophenone
      from 1*+; cyclopropyl(4-methoxyphenyl) ketone and 4,4'-dimethoxybenzophenone from
      2*+) have been rationalized in terms of a water-induced competition between O
      neophyl shift and C-cyclopropyl beta-scission in the intermediate 1,1
      diarylalkoxyl radicals 1r* and 2r*.

PMID- 16599614
TI  - Explorations on the total synthesis of the unusual marine alkaloid chartelline A.
AB  - In work directed toward a total synthesis of chartelline A (1a), a strategy was
      investigated to construct the 10-membered ring of this marine alkaloid via an
      intramolecular aldehyde/beta-lactam cyclocondensation to form the macrocyclic
      enamide functionality. Therefore, spiro-beta-lactam and imidazole fragments were
      first prepared. Tribromooxindole beta-lactam 24 was synthesized from commercially
      available 5-nitroisatin (18) in seven steps and 30% overall yield via a
      Staudinger ketene-imine [2 + 2]-cycloaddition strategy. The requisite 2
      bromoimidazole subunit 40 bearing a terminal alkyne and a masked aldehyde was
      efficiently prepared from the readily available imidazole ester 25 in 10 steps.
      With both advanced intermediates available, the addition of the lithium acetylide
      generated from 2-bromoimidazole subunit 40 to the gamma-lactam carbonyl group of
      N-Boc-tribromooxindole 24 was investigated, affording the desired N-Boc-aminal
      41. Hydrolysis of the acetonide moiety of 41, followed by oxidative cleavage of
      the resulting diol, gave the aldehyde 42. Unfortunately, treatment of aldehyde 42
      with p-toluenesulfonic acid did not give the desired 10-membered macrocyclic (Z)
      enamide 46, but rather the highly unsaturated seven-membered ring compound 44.

PMID- 16599616
TI  - Synthesis and structure revision of calyxin natural products.
AB  - Tandem Prins cyclization and Friedel-Crafts reaction with an electron-rich
      aromatic ring were used to prepare the core structures of calyxin natural
      products. The proposed structure of epicalyxin F was prepared and shown to be
      incorrect. Several calyxin natural products, including calyxin F and L, were
      synthesized, and the structures were reassigned on the basis of NMR data and
      synthetic correlations.

PMID- 16599617
TI  - Tetrasubstituted olefin synthesis via Pd-catalyzed addition of arylboronic acids
      to internal alkynes using O2 as an oxidant.
AB  - The Pd(II)-catalyzed reaction of arylboronic acids and internal alkynes provides
      a convenient route to a wide variety of tetrasubstituted olefins. The reaction is
      conducted in DMSO using molecular O2 as an oxidant in the absence of any base.
      The reaction involves the cis addition of two aryl groups from the arylboronic
      acid to opposite ends of the triple bond of the internal alkyne. The synthesis
      tolerates a wide variety of functional groups, including alcohol, aldehyde,
      ester, TMS, and acetal groups. Electron-rich dialkylacetylenes, such as 4-octyne,
      provide highly substituted 1,3-dienes in moderate yields. The very mild O2/DMSO
      conditions also afford good to excellent yields of biaryls by the homocoupling of
      arylboronic acids.

PMID- 16599618
TI  - Generation and cyclization of unsaturated carbamoyl radicals derived from S-4
      pentynyl carbamothioates under tin-free conditions.
AB  - The radical reaction of benzenethiol with S-4-pentynyl carbamothioates provides a
      valuable protocol for the tin-free generation of carbamoyl radicals, which arise
      from intramolecular substitution at sulfur by the initial sulfanylvinyl radicals.
      This procedure can be usefully employed to achieve N-benzylcarbamoyl radical 5
      exo and 4-exo cyclizations leading, respectively, to pyrrolidinones and
      azetidinones, although, for the latter, it seems of lesser utility. Novel
      evidence is presented that N-tosyl-substituted carbamoyl radicals display a
      peculiar tendency to yield the corresponding isocyanate by beta-elimination of
      the tosyl radical.

PMID- 16599619
TI  - Facile N-arylation of amines and sulfonamides and o-arylation of phenols and
      arenecarboxylic acids.
AB  - An efficient, transition-metal-free procedure for the N-arylation of amines,
      sulfonamides, and carbamates and O-arylation of phenols and carboxylic acids has
      been achieved by allowing these substrates to react with a variety of o-silylaryl
      triflates in the presence of CsF. Good to excellent yields of arylated products
      are obtained under very mild reaction conditions. This chemistry readily
      tolerates a variety of functional groups.

PMID- 16599621
TI  - 4-Alkoxycarbonyl- and aminocarbonyl-substituted isoxazoles as masked acrylates
      and acrylamides in the asymmetric synthesis of delta2-isoxazolines.
AB  - 4-Alkoxycarbonyl and aminocarbonyl-substituted isoxazoles undergo conjugate
      reduction to give delta2-isoxazolines on treatment with sodium borohydride and
      sodium trifluoroacetoxyborohydride, respectively. They are also alkylated at C5
      through sonication with secondary and tertiary alkyl iodides in the presence of
      zinc dust and copper(I) iodide. These reactions are analogous to those observed
      with acrylates and acrylamides. The behavior is characteristic of the 4
      substituted isoxazoles but not the 5-substituted regioisomers. The reductions of
      4,5-disubstituted isoxazoles and the C5 alkylations of 4-substituted isoxazoles
      generally afford trans-4,5-disubstituted isoxazolines. Incorporating chiral
      auxiliaries into the alkoxycarbonyl group maintains this relative
      stereoselectivity. It does not provide significant levels of asymmetric induction
      in the reductions, but the alkylations occur with good levels of stereocontrol at
      both C4 and C5. Because both enantiomers of the auxiliaries are available, this
      provides access to either enantiomer of the products, in 93 to > or = 98% de. The
      methodology, therefore, provides a complementary approach to nitrile oxide
      cycloadditions to alkenes for the asymmetric synthesis of delta2-isoxazolines.

PMID- 16599620
TI  - Rhodium(I)-catalyzed nucleophilic ring-opening reactions of oxabicyclo adducts
      derived from the [4 + 2]-cycloaddition of 2-imido-substituted furans.
AB  - A series of 2-imido-substituted furans containing tethered unsaturation were
      prepared by the addition of the lithium carbamate of furan-2-ylcarbamic acid tert
      butyl ester to a solution of the mixed anhydride of an appropriately substituted
      3-butenoic acid. The initially formed imido furans undergo a rapid intramolecular
      [4 + 2]-cycloaddition at room temperature to deliver the Diels-Alder cycloadducts
      in good to excellent yield. Isolation of the highly labile oxabicyclic adduct is
      believed to be a consequence of the lower reaction temperatures employed as well
      as the presence of the extra carbonyl group, which diminishes the basicity of the
      nitrogen atom, thereby retarding the ring cleavage/rearrangement reaction
      generally encountered with related systems. By using a Rh(I)-catalyzed ring
      opening of the oxabicyclic adduct with various nucleophilic reagents, it was
      possible to prepare highly functionalized hexahydro-1H-indol-2(3H)-one
      derivatives in good yield. The major stereoisomer obtained possesses a cis
      relationship between the nucleophile and hydroxyl group in the ring-opened
      product. The stereochemistry was unequivocally established by X-ray
      crystallographic analysis. Coordination of Rh(I) to the alkenyl pi-bond followed
      by a nitrogen-assisted cleavage of the carbon-oxygen bond occurs to furnish a pi
      allyl rhodium(III) species. Addition of the nucleophile then occurs from the
      least hindered terminus of the resulting pi-allyl rhodium(III) complex. Proton
      exchange followed by rhodium(I) decomplexation ultimately leads to the cis
      diastereomer.

PMID- 16599622
TI  - Circular dichroism of intra- and intermolecular charge-transfer complexes.
      Enhancement of anisotropy factors by dimer formation and by confinement.
AB  - The dynamic behavior of new CT-dyads (CT = charge transfer) has been studied by
      means of UV-vis, fluorescence, and NMR spectroscopies under a variety of
      conditions. It was found that the CT-dyads exhibit conformational variations,
      such as extended and folded monomers and an antiparallel dimer complex, depending
      on the conditions. The CT interaction was found in the folded conformation at
      ambient temperature, while the contribution of the dimeric species became evident
      at lower temperatures. Most interestingly, close examinations of the circular
      dichroism spectra of these CT-dyads reveal that the anisotropy (g) factors of the
      dimers are significantly enhanced by a factor of approximately 30 in the CT
      transition region. Such enhancement is rationalized in terms of the stronger CT
      interactions in the dimer through the double electronic coupling element, which
      imposes stronger restrictions on the rotation of alkyl group(s). Confinement of
      the CT-dyads in cyclodextrin (CD) and cucurbituril cavities afforded further
      insights into the chiroptical properties of the CT-dyad. The effects of
      confinement are clearly size-dependent, exhibiting a substantial enhancement of
      the g factors by a factor of 5-10 upon inclusion by beta-CD and also by
      cucurbit[8]uril, but with no appreciable changes upon complexation with the other
      CDs. These results indicate that the conformational fixation of CT-dyads, for
      example by dimer formation or by confinement in size/shape-matched cavities, is a
      conventional, yet powerful, tool for manipulating (mostly enhancing) the
      chiroptical properties of the CT transition, which should be applicable in
      general to a variety of molecular and supramolecular CT systems.

PMID- 16599623
TI  - Design and synthesis of a photocleavable fluorescent nucleotide 3'-O-allyl-dGTP
      PC-Bodipy-FL-510 as a reversible terminator for DNA sequencing by synthesis.
AB  - DNA sequencing by synthesis (SBS) using reversible fluorescent nucleotide
      terminators is potentially an efficient approach to address the limitations of
      current DNA sequencing techniques. Here, we report the design and synthesis of a
      3'-O-allyl photocleavable fluorescent nucleotide analogue, 3'-O-allyl-dGTP-PC
      Bodipy-FL-510, as a reversible terminator for SBS. The nucleotide is efficiently
      incorporated by DNA polymerase into a growing DNA strand to terminate the
      polymerase reaction. After that, the fluorophore is photocleaved quantitatively
      by irradiation at 355 nm, and the allyl group is rapidly and efficiently removed
      by using a Pd-catalyzed reaction under DNA-compatible conditions to regenerate a
      free 3'-OH group to reinitiate the polymerase reaction. Two cycles of such steps
      were successfully demonstrated to sequence a homopolymeric region of a DNA
      template, facilitating the development of SBS as a viable approach for high
      throughput DNA sequencing.

PMID- 16599625
TI  - Synthesis of dithieno[2,3-b:3',2'-d]thiophenes-building blocks for cross
      conjugated beta-oligothiophenes.
AB  - Syntheses of annelated and functionalized beta-trithiophenes (dithieno[2,3
      b:3',2'-d]thiophenes), building blocks for the helically annelated, cross
      conjugated beta-oligothiophenes, are reported. UV-vis spectra reveal that the
      effect of octyl substituents on the onset of electronic absorption in annelated
      beta-trithiophenes is negligible compared to the effect of helical distortion in
      the higher beta-oligothiophenes.

PMID- 16599624
TI  - Experimental and theoretical studies on stereo- and regioselectivity in
      intramolecular nitrone-alkene cycloaddition of hept-6-enoses derived from
      carbohydrates.
AB  - The effect of blocking groups and stereochemistry of the substituents on the
      regio- and stereoselectivity in intramolecular nitrone-alkene cycloaddition
      (INAC) of hept-6-enoses are reported. L-ribo-Hept-6-enose 12 and D-lyxo-hept-6
      enose 15, both containing a 2,3-O-isopropylidene blocking group, and L-xylo-hept
      6-enose 23 and D-arabino-hept-6-enose 30, both with a 2,3-O-trans-diacetal
      blocking group, were prepared from D-ribose and D-arabinose, respectively. With N
      alkyl hydroxylamine, lactols 12 and 15 underwent an INAC reaction to give cis
      fused isoxazolidines exclusively whereas lactols 23 and 30 gave a mixture of cis
      , trans-fused isoxazolidines (cyclohexanols) and bridged isoxazolidines
      (cycloheptanols). With the 2,3-O-trans-diacetal protecting group, the bridged
      bicyclo[4.2.1]isoxazolidines (cycloheptanols), via the endo mode of INAC
      cyclization, were synthesized for the first time from unbranched sugar
      derivatives 23 and 30. The stereochemical outcomes of these reactions were
      rationalized on the basis of transition state energies obtained by computation.
      The present INAC showed trivial temperature, but significant solvent dependence.
      For lactols 23 and 30, performing the INAC in 2-propanol gave the best yields of
      fused isoxazolidines (cyclohexanols) whereas in dichloromethane afforded the best
      yields of bridged isoxazolidines (cycloheptanols).

PMID- 16599626
TI  - Fumarate of (S,S)-alpha,alpha'-bis(trifluoromethyl)-1,8-anthracenedimethanol. A
      chiral macrocycle for the Diels-Alder reaction with cyclopentadiene.
AB  - The synthesis and structural study of the fumarate of (S,S)-alpha,alpha'
      bis(trifluoromethyl)-1,8-anthracenedimethanol by NMR spectroscopy are reported.
      The conformational study of the 13-membered macrocycle is presented. The cited
      alcohol is assayed as a chiral auxiliary in a Diels-Alder reaction with
      cyclopentadiene, and after methanolysis, provides the norbornene derivative with
      high enantioselectivity.

PMID- 16599628
TI  - Solvent- and temperature-tuned orientation of ferrocenyl azide inside beta
      cyclodextrin.
AB  - An induced circular dichroism (ICD) solution study on the orientation of
      ferrocenyl azide within the beta-cyclodextrin cavity is described. In DMSO,
      ferrocenyl azide prefers an axial inclusion, whereas in ethylene glycol and
      DMSO/H2O = 50/50 an equatorial alignment dominates. As shown by temperature
      dependent ICD spectra, at lower temperatures ferrocenyl azide adopts
      preferentially an equatorial arrangement, whereas at higher temperatures an axial
      one is favored. Temperature and solvent effects on the co-conformation of
      ferrocene noncovalently bound to cyclodextrin have never been observed before.

PMID- 16599627
TI  - Regioselective copper-catalyzed amination of bromobenzoic acids using aliphatic
      and aromatic amines.
AB  - A chemo- and regioselective copper-catalyzed cross-coupling procedure for
      amination of 2-bromobenzoic acids is described. The method eliminates the need
      for acid protection and produces N-aryl and N-alkyl anthranilic acid derivatives
      in up to 99% yield. N-(1-Pyrene)anthranilic acid has been employed in metal ion
      selective fluorosensing. Titration experiments showed that this pyrene-derived
      amino acid forms an equimolar complex with Hg(II) in water resulting in selective
      fluorescence quenching even in the presence of other metal ions such as Zn(II)
      and Cd(II).

PMID- 16599629
TI  - Asymmetric synthesis of four isomers of 2-C-trifluoromethylerythritol.
AB  - Optically active 2-C-trifluoromethylerythritols, analogues of 2-C
      methylerythritol, which is a key intermediate in the biosynthesis of isoprenoid
      with a mevalonate-independent route, were conveniently synthesized from 1,1,1
      trifluoro-2,3-epoxypropane.

PMID- 16599630
TI  - Controlling olefin geometry with Pd catalysis: selective formation of Z-olefins
      from both E- and Z-allylic carbonates.
AB  - The palladium-catalyzed formation of Z-olefins from allylic carbonates and a
      variety of protected dialkyl aminomalonates is reported. The reaction is
      selective for the Z-isomer, and either acetyl, Boc, or formyl protecting groups
      are tolerated. The Z-olefin product can be formed regardless of whether the E- or
      Z-allylic carbonate is used as starting material.

PMID- 16599631
TI  - Rapid conversion of hindered arylsulfonates to alkyl chlorides with retention of
      configuration.
AB  - Arylsulfonates of hindered secondary alcohols are converted to the corresponding
      alkyl chlorides very rapidly and in good yields in the presence of titanium
      tetrachloride at low temperatures. These reactions proceed with exclusive
      retention of configuration.

PMID- 16599632
TI  - Synthesis of (-)-stemoamide using a stereoselective anti-aldol step.
AB  - The synthesis of (-)-stemoamide was achieved in 11 steps from 5-acetoxy-N-crotyl
      pyrrolidinone. A chiral N-acyl thiazolidinethione was employed in a
      stereoselective addition to a cyclic N-acyl iminium ion to install the required
      stereochemistry of carbon C9a. This iminium ion addition product was employed in
      a stereoselective MgBr2-catalyzed anti-aldol reaction to install the required
      stereochemistry of carbons C8 and C9. The X-ray crystal analysis of (-)
      stemoamide confirmed the structure and the stereochemical outcome of these
      selective reactions.

PMID- 16599633
TI  - Palladium-mediated intramolecular aryl amination on furanose derivatives: an
      expedient approach to the synthesis of chiral benzoxazocine derivatives and
      tricyclic nucleosides.
AB  - Pd-catalyzed intramolecular arylamination on sugar derivatives has been
      accomplished by using bulky biaryl phosphine ligands. An application of this
      methodology on a variety of D-glucose-derived substrates, 2a-f, led to the
      synthesis of highly functionalized cis-fused tricyclic oxazocines, 3a-e. The
      products could subsequently be transformed to the optically active benzoxazocine
      derivative 4 and tricyclic nucleoside 6. This is the first example of the
      synthesis of eight-membered rings via intramolecular cycloamination of furanose
      derivatives, which provides a very useful method for the catalytic synthesis of
      medium-ring heterocycles.

PMID- 16599634
TI  - De novo synthesis of sugar-aza-crown ethers via a domino Staudinger aza-Wittig
      reaction.
AB  - A short and highly efficient route to sugar-aza-crown (SAC) ethers has been
      developed. The key step of the transformation is a one-pot cyclodimerization of C
      glycosyl azido aldehydes via a domino Staudinger aza-Wittig reaction. This
      process allows the preparation of various orthogonally protected SAC ethers, from
      both alpha- and beta-C-glycosyl azido aldehydes.

PMID- 16599636
TI  - A new total synthesis of porritoxin.
AB  - A concise and efficient total synthesis of the phytotoxin porritoxin is
      described. The key step of the synthesis is based upon a Parham cyclization
      methodology which enables the creation of the lactam unit embedded in the title
      compound framework with the concomitant formation of the tethered hydroxyakyl
      chain.

PMID- 16599635
TI  - Fluorous (trimethylsilyl)ethanol: a new reagent for carboxylic acid tagging and
      protection in peptide synthesis.
AB  - Starting with a fluorous analogue of 2-(trimethylsilyl)ethanol, we have designed
      an easy method for preparing a new fluorous tag ((F)TMSE) for the protection of
      carboxylic acids. Because mild conditions are employed in the tag cleavage (TBAF
      in the presence of 4 A molecular sieves, which prevent racemization), this tag
      can be advantageously used in the synthesis of peptides and modified peptides, as
      we have demonstrated with several examples, including the fluorous synthesis of
      short alpha- and beta-peptides as well as of modified fluorinated retropeptides.

PMID- 16599637
TI  - Stereospecific ester activation in nitrite-mediated carbohydrate epimerization.
AB  - [reaction: see text] The Lattrell-Dax method of nitrite-mediated substitution of
      carbohydrate triflates is an efficient method to generate structures of inverse
      configuration. In the present study, epimerization of gluco- and
      galactopyranoside derivatives to the corresponding allo- and gulopyranoside
      structures by triflation/nitrite treatment has been investigated. It was found
      that a neighboring ester group was essential for the reactivity of the nitrite
      mediated triflate inversion. Furthermore, a good inversion yield also depended on
      the relative configuration of the neighboring ester group to the triflate. Only
      with the ester group in the equatorial position, whatever the configuration of
      the triflate, did the reaction proceed smoothly, whereas a neighboring axial
      ester group proved largely inefficient. The results were subsequently used to
      predict the inversion of glucopyranoside derivatives to the mannopyranoside
      epimers.

PMID- 16599638
TI  - Stereoselective synthesis of protected (2R,3R,4S)-4,7-diamino-2,3
      dihydroxyheptanoic acid: a novel amino acid of callipeltins A and D.
AB  - An orthogonally protected derivative 1 of (2R,3R,4S)-4,7-diamino-2,3
      dihydroxyheptanoic acid, the unusual amino acid residue of the biologically
      active marine peptides such as callipeltins A and D and neamphamide A, was
      efficiently prepared in 10 steps and 30% overall yield from a commercially
      available L-ornithine derivative 2. The key step includes the N-diphenylmethylene
      controlled diastereoselective dihydroxylation of (Z)-ester 3 with >13:1
      selectivity for the desired isomer.

PMID- 16599640
TI  - An efficient enantioselective approach to cyclic beta-amino acid derivatives via
      olefin metathesis reactions.
AB  - The asymmetric synthesis of polyfunctionalized piperidine- and pyrrolidine-based
      scaffolds, specifically designed for the preparation of cyclic, conformationally
      constrained beta-amino acids, is realized combining a biocatalytic access to a
      versatile chiral building block with a wide range of transformations based on
      olefin metathesis.

PMID- 16599639
TI  - Synthesis of a novel dicyano abietane analogue: a potential antiinflammatory
      agent.
AB  - From a structure-activity relationship perspective, the new abietane 5 having
      cyano groups at C-2 and C-13 and a phenolic ring C has been synthesized and
      evaluated biologically because the related compound 4 has high potency in
      inflammation models in vitro and in vivo. Compound 5 was synthesized from 8,
      which was obtained in five steps from the known compound 9, via an unexpected
      aromatization caused by the addition of PhSeCl and subsequent
      oxidation/elimination of the selenated intermediate 14 with H2O2.

PMID- 16599641
TI  - Radical-mediated opening of 2,3-epoxy alcohols using Cp2TiCl: stereoselective
      construction of quaternary chiral centers.
AB  - Radical-mediated opening of chiral 2,3-epoxy alcohols regioselectively at the 2
      position using Cp2TiCl and trapping the intermediate radical with methyl acrylate
      and acrylonitrile led to the stereoselective formation of tetrasubstituted chiral
      centers.

PMID- 16599642
TI  - Synthesis of indenes via palladium-catalyzed carboannulation of diethyl 2-(2-(1
      alkynyl)phenyl)malonate and organic halides.
AB  - Highly substituted indenes have been prepared in good yields by the palladium
      catalyzed carboannulation of diethyl 2-(2-(1-alkynyl)phenyl)malonate with aryl,
      benzylic, and alkenyl halides. The reaction conditions and the scope of the
      process were examined, and a possible mechanism is proposed.

PMID- 16599643
TI  - Effect of M(CO)3 (M = Cr, Mn+) on aromatic C-Cl BDE in (eta6-ArCl)M(CO)3
      complexes.
AB  - The coordination of Cr(CO)3 to chlorobenzenes significantly reduces the C-Cl bond
      dissociation energy. Treatment of chloroarene-Cr(CO)3 complexes with SmI2/HMPA at
      room temperature led to complete dechlorination. Reaction of o
      allyloxychlorobenzene-Cr(CO)3 complexes with SmI2 at room temperature resulted in
      the corresponding dechlorinative cyclization products in good to excellent
      yields. Competition experiments indicated the following relative reactivities of
      dehalogenation by SmI2: PhI/PhCl-Cr(CO)3/PhBr/PhCl = 50:1:0.3:<0.001. On the
      other hand, the coordination of Mn(CO)3(+) to chlorobenzene showed a much smaller
      activation effect. Density functional theory calculations revealed that the spin
      delocalization effect of the metal center plays an important role in the C-Cl
      bond activation.

PMID- 16599644
TI  - Efficient synthesis of beta2-amino acid by homologation of alpha-amino acids
      involving the Reformatsky reaction and Mannich-type imminium electrophile.
AB  - Development of new methods for the synthesis of beta-amino acids is important as
      polymers of these compounds are promising peptidomimetic candidates in medicinal
      chemistry. We report here our findings on a new and highly efficient general
      strategy for the synthesis of beta2-amino acids by homologation of alpha-amino
      acids, involving the Reformatsky reaction and Mannich-type imminium electrophile.

PMID- 16599645
TI  - Aromatherapy in the management of psychiatric disorders: clinical and
      neuropharmacological perspectives.
AB  - Aromatherapy is currently used worldwide in the management of chronic pain,
      depression, anxiety, some cognitive disorders, insomnia and stress-related
      disorders. Although essential oils have been used, reputedly effectively, for
      centuries as a traditional medicine, there is very little verified science behind
      this use. The pharmacology of the essential oils and/or their single chemical
      constituents, therefore, remains largely undiscovered. However, accumulating
      evidence that inhaled or dermally applied essential oils enter the blood stream
      and, in relevant molecular, cellular or animal models, exert measurable
      psychological effects, indicates that the effects are primarily
      pharmacological.This review includes evidence from the limited number of clinical
      trials that have been published of 'psychoaromatherapy' in relation to
      psychiatric disorders, together with evidence from mechanistic,
      neuropharmacological studies of the effects of essential oils in relevant in
      vitro and in vivo models. It is concluded that aromatherapy provides a
      potentially effective treatment for a range of psychiatric disorders. In
      addition, taking into account the available information on safety, aromatherapy
      appears to be without the adverse effects of many conventional psychotropic
      drugs. Investment in further clinical and scientific research is clearly
      warranted.

PMID- 16599646
TI  - Tailoring nicotine replacement therapy: rationale and potential approaches.
AB  - Nicotine replacement therapy (NRT) is an effective treatment for smoking
      cessation, but as with all such pharmacotherapies, the majority of smokers who
      use NRT products do not stop smoking or remain abstinent long term. Treatment
      outcome is affected by a range of individual-specific factors, as well as the
      pharmacokinetic profile of each NRT formulation. This has led to speculation that
      abstinence rates could be improved if NRT treatments were individually tailored
      to best match each individual's needs and preferences. There are also populations
      for whom special product and dosage considerations are warranted to maximise
      treatment safety.This paper reviews the rationale for NRT treatment, standard
      dose recommendations and recommendations for how to best match NRT treatment to
      the specific needs of individual smokers. We also review emerging evidence that
      genetic profiling may one day be a useful consideration for tailoring NRT
      treatment.

PMID- 16599647
TI  - The SOHO (Schizophrenia Outpatient Health Outcome) study: implications for the
      treatment of schizophrenia.
AB  - The European SOHO (Schizophrenia Outpatient Health Outcome) study is an
      observational, naturalistic study of the outpatient treatment of schizophrenia.
      The patient recruitment and assessment began in September 2000 and finished in
      early 2005. A total of 10 972 adult patients from ten European countries who were
      initiating or changing antipsychotic medication for the treatment of
      schizophrenia within the normal course of care have been enrolled. The patients
      have been followed at regular intervals over the 3-year timeframe of the study.
      Evaluation includes clinical severity, measured with the Clinical Global
      Impression (CGI) scale; health-related quality of life; social functioning; and
      medication tolerability. The 6- and 12-month results have been published so far
      and have demonstrated that the patients in whom treatment was initiated with
      olanzapine or clozapine or who were started on more than one antipsychotic of any
      class at baseline tended to have somewhat greater improvement than patients
      treated with other atypical or typical antipsychotics, both in terms of symptoms
      measured with the CGI and quality of life. Numbers of social contacts increased
      with the treatment, but other aspects of social functioning did not show any
      significant change. Atypical antipsychotics as a class were associated with a
      lower frequency of extrapyramidal symptoms (EPS) and anticholinergic use than
      typical antipsychotics. The frequency of EPS was lowest in the clozapine-,
      quetiapine- and olanzapine-treated patients, at around 10%. The atypical
      antipsychotics also conferred a lower risk for tardive dyskinesia than the
      typical antipsychotics. Weight gain occurred in all treatment cohorts over the
      first 12 months of treatment and was statistically significantly greater in the
      patients who started treatment with olanzapine and clozapine. Prolactin- and
      sexually-related adverse events were frequent at baseline assessment: amenorrhoea
      was present in around one- third of women, impotence in around 40% of men, and
      loss of libido in 50% of both male and female patients. Patients treated with
      olanzapine, clozapine and quetiapine were significantly less likely to have
      sexual/endocrine-related dysfunctions after 6 months of treatment (the 12-month
      results of this parameter are yet to be published) than those in the other
      treatment cohorts (typical antipsychotics, risperidone and amisulpride).
      Concomitant medication use during the study has been high, ranging from 5% to 29%
      for anticholinergics, 8% to 23% for antidepressants, 22% to 37% for anxiolytics
      and 7% to 19% for mood stabilisers, depending on the type of antipsychotic
      prescribed. Fewer olanzapine-, quetiapine- and clozapine-treated patients used
      concomitant anticholinergics or anxiolytics/hypnotics. The current results from
      the SOHO study indicate that differences in effectiveness and tolerability do
      exist between the antipsychotics. Future results from the study will be published
      during the coming months and years, and will allow patterns of antipsychotic use
      in routine clinical practice (including how often and why changes are made) to be
      determined. This important information is likely to impact on the future use of
      antipsychotics and will assist clinicians in refining the use of these drugs and
      improving the outcome of patients to whom they are prescribed.

PMID- 16599648
TI  - Long-term prophylaxis in bipolar disorder.
AB  - Bipolar disorder is a major cause of disability, and the prevention of relapse is
      a key management goal. Pharmacological interventions, effectively delivered
      through enhanced clinical care, are central to long-term management. This article
      summarises the available evidence for a range of pharmacological options, and
      provides guidance on common issues in clinical management in line with current
      practice guidelines. The use of medications for long-term prophylaxis should be
      considered in all patients meeting criteria for bipolar I disorder. Increasing
      high-quality evidence from randomised trials informs management decisions
      relating to both novel agents, such as lamotrigine and olanzapine, and longer
      established therapies, such as lithium and valproate, in monotherapy. Medications
      taken long-term in bipolar disorder differ in the extent to which they protect
      against manic and depressive relapse. Consequently, the emerging challenge is to
      understand how combination treatments can enhance efficacy and effectiveness
      based on data from controlled trials rather than random polypharmacy. Clinical
      care can be enhanced with effective education about the illness, and the use of
      strategies to improve treatment adherence and the recognition and management of
      stressors or prodromal symptoms. Where available, a range of specific
      psychological interventions can be effective as an adjunct to medication. When
      discontinuation of prophylaxis is necessary, gradual tapering of dose over weeks
      or months is recommended.

PMID- 16599650
TI  - Reports of acute angle closure glaucoma-related adverse events with SSRIs:
      results of a disproportionality analysis.

PMID- 16599649
TI  - Assessing therapeutic efficacy in a progressive disease: a study of donepezil in
      Alzheimer's disease.
AB  - OBJECTIVE: To determine the value of continued donepezil treatment in patients
      with Alzheimer's disease for whom clinical benefit was initially judged to be
      uncertain. METHODS: The study consisted of three phases: (i) a 12- to 24-week,
      pre-randomisation, open-label donepezil-treatment phase; (ii) a 12-week,
      randomised, double-blind, placebo-controlled phase; and (iii) a 12-week, single
      blind (i.e. patient-blind) donepezil-treatment phase. Patients with mild to
      moderate Alzheimer's disease received open-label treatment with donepezil (5
      mg/day for 4 weeks, then 10 mg/day for the remainder of the phase) for 12-24
      weeks. Patients who exhibited a decline or no change from baseline on the Mini
      Mental State Examination (MMSE) and whose physician was not sufficiently certain
      of clinical benefit to warrant continued treatment were randomised into the
      double-blind phase in which patients received 12 weeks of treatment with
      donepezil (10 mg/day) or placebo. At the end of the double-blind phase, donepezil
      treated patients continued to receive donepezil, while placebo-treated patients
      were rechallenged with donepezil, in a 12-week single-blind phase. Patients were
      assessed at the start of the double-blind phase and at weeks 6 and 12 of this
      phase, and at the end of the single-blind phase. RESULTS: Six hundred and
      nineteen patients completed the open-label phase; 69% showed clear clinical
      benefit and 31% showed uncertain benefit. 202 patients were randomised to
      continued donepezil treatment (n = 99) or placebo (n = 103). Differences in
      favour of continued donepezil versus placebo were observed in cognition and
      behaviour. In addition, there was a non-significant trend favouring donepezil in
      activities of daily living (ADL) [week 12 observed case mean treatment
      differences: MMSE, 1.13 (p = 0.02); Alzheimer's Disease Assessment Scale -
      cognitive subscale, 0.57 (p = 0.5); the Neuropsychiatric Inventory, -3.16 (p =
      0.02); Disability Assessment for Dementia scale, 3.67 (p = 0.1)]. CONCLUSION:
      Most patients showed clear clinical benefit during initial donepezil treatment.
      Among patients for whom clinical benefit was uncertain, improvement in cognition
      and behaviour were observed for those who continued donepezil treatment compared
      with the group switched to placebo. Initial decline or stabilisation does not
      necessarily indicate a lack of efficacy in Alzheimer's disease, and the decision
      to discontinue treatment should be based on an evaluation of all domains
      (cognition, behaviour and ADL) and performed at several timepoints.

PMID- 16599651
TI  - Ziconotide.
AB  - Ziconotide, an intrathecal analgesic for the management of chronic intractable
      pain, binds with high affinity to N-type calcium channels in neuronal tissue and
      obstructs neurotransmission. In three pivotal, well designed trials of 5-6 or 21
      days' duration, titrated ziconotide was significantly more effective than placebo
      in treating chronic malignant or nonmalignant pain as assessed by mean percentage
      improvements from baseline in Visual Analogue Scale Pain Intensity scores.
      Improvements in secondary endpoints (e.g. proportion of patients who responded or
      achieved pain relief and the change in opioid use) generally support the efficacy
      of ziconotide over placebo. Ziconotide maintains its analgesic efficacy in
      preliminary results from long-term, open-label trials (data available for up to
      12 months). Most ziconotide-related adverse events are neurological, mild to
      moderate in severity, resolve over time and reverse without sequelae on drug
      discontinuation. Low initial doses of ziconotide and gradual titration to onset
      of analgesia reduces the incidence and severity of adverse events. No evidence of
      respiratory depression has been reported with intrathecal ziconotide.

PMID- 16599654
TI  - Formation of capillary bridges in two-dimensional atomic force microscope-like
      geometry.
AB  - We discuss the phase diagram of a fluid confined in a two-dimensional atomic
      force microscope-like geometry which allows the formation of liquid bridges
      connecting the opposite walls. The corresponding phase behavior of the fluid is
      influenced by the phenomenon of complete filling of a wedge.

PMID- 16599655
TI  - Toward uniform nanotubular compounds: synthetic approach and ab initio
      calculations.
AB  - We propose to synthesize a new class of single-walled nanotubular compounds
      (SWNCs) and investigate the interplay between their structural and electronic
      properties using ab initio density functional calculations. SWNCs are composed of
      cyclacenes of variable diameter interconnected by various linker compounds.
      Cyclacenes map directly onto and can be viewed as the shortest segments of (n,0)
      zigzag carbon nanotubes. We focus on cyclacenes with n=6-12 fused benzene rings
      interconnected by biphenyl, tetrazine, or acetylene linkers. Depending upon the
      nature and the orientation of the linkers, we find it possible to change the
      systems from narrow-gap to wide-gap semiconductors, and to modulate the band
      dispersion, suggesting the possibility of band gap engineering.

PMID- 16599656
TI  - SPOCK.CI: a multireference spin-orbit configuration interaction method for large
      molecules.
AB  - We present SPOCK.CI, a selecting direct multireference spin-orbit configuration
      interaction (MRSOCI) program based on configuration state functions. It
      constitutes an extension of the spin-free density functional
      theory/multireference configuration interaction (DFT/MRCI) code by Grimme and
      Waletzke [J. Chem. Phys. 111, 5645 (1999)] and includes spin-orbit interaction on
      the same footing with electron correlation. Key features of SPOCK.CI are a fast
      determination of coupling coefficients between configuration state functions, the
      use of a nonempirical effective one-electron spin-orbit atomic mean-field
      Hamiltonian, the application of a resolution-of-the-identity approximation to
      computationally expensive spin-free four-index integrals, and the use of an
      efficient multiroot Davidson diagonalization scheme for the complex Hamiltonian
      matrix. SPOCK.CI can be run either in ab initio mode or as semiempirical
      procedure combined with density functional theory (DFT/MRSOCI). The application
      of these techniques and approximations makes it possible to compute spin
      dependent properties of large molecules in ground and electronically excited
      states efficiently and with high confidence. Second-order properties such as
      phosphorescence rates are known to converge very slowly when evaluated
      perturbationally by sum-over-state approaches. We have investigated the
      performance of SPOCK.CI on these properties in three case studies on 4H-pyran-4
      thione, dithiosuccinimide, and free-base porphin. In particular, we have studied
      the dependence of the computed phosphorescence lifetimes on various technical
      parameters of the MRSOCI wave function such as the size of the configuration
      space, selection of single excitations, diagonalization thresholds, etc. The
      results are compared to the outcome of extensive quasidegenerate perturbation
      theory (QDPT) calculations as well as experiment. In all three cases, the MRSOCI
      approach is found to be superior to the QDPT expansion and yields results in very
      good agreement with experimental findings. For molecules up to the size of free
      base porphin, MRSOCI calculations can easily be run on a single-processor
      personal computer. Total CPU times for the evaluation of the electronic
      excitation spectrum and the phosphorescence lifetime of this molecule are below
      40 h.

PMID- 16599657
TI  - Full configuration interaction approach to the few-electron problem in artificial
      atoms.
AB  - We present a new high performance configuration interaction code optimally
      designed for the calculation of the lowest-energy eigenstates of a few electrons
      in semiconductor quantum dots (also called artificial atoms) in the strong
      interaction regime. The implementation relies on a single-particle
      representation, but it is independent of the choice of the single-particle basis
      and, therefore, of the details of the device and configuration of external
      fields. Assuming no truncation of the Fock space of Slater determinants generated
      from the chosen single-particle basis, the code may tackle regimes where Coulomb
      interaction very effectively mixes many determinants. Typical strongly correlated
      systems lead to very large diagonalization problems; in our implementation, the
      secular equation is reduced to its minimal rank by exploiting the symmetry of the
      effective-mass interacting Hamiltonian, including square total spin. The
      resulting Hamiltonian is diagonalized via parallel implementation of the Lanczos
      algorithm. The code gives access to both wave functions and energies of first
      excited states. Excellent code scalability in a parallel environment is
      demonstrated; accuracy is tested for the case of up to eight electrons confined
      in a two-dimensional harmonic trap as the density is progressively diluted up to
      the Wigner regime, where correlations become dominant. Comparison with previous
      quantum Monte Carlo simulations in the Wigner regime demonstrates power and
      flexibility of the method.

PMID- 16599658
TI  - Cooperative effects in photon statistics of molecular dimers with spectral
      diffusion.
AB  - The two-point fluorescence intensity correlation function g(2)t and the Mandel
      parameter Mt are calculated for a strongly pumped dimer of two-level molecules
      undergoing Gaussian-Markovian frequency fluctuations. The effects of detuning and
      saturation are examined. All fluctuation time scale regimes are explored using a
      continued fraction solution of the stochastic Liouville equation for the
      generating function. Bunching and antibunching are observed for slow and fast
      fluctuations, respectively. The short-time antibunching dip in g(2) and its
      variation with intermolecular coupling, the exciton annihilation rate, and laser
      detuning are studied.

PMID- 16599659
TI  - Electron density fitting for the Coulomb problem in relativistic density
      functional theory.
AB  - A density fitting approach for the Coulomb matrix representation within the four
      component formulation of relativistic density-functional theory is presented. Our
      implementation, which uses G-spinor basis sets, shares all the advantages of
      those found in nonrelativistic quantum chemistry. We show that very accurate
      Coulomb energies may be obtained using a modest number of scalar auxiliary basis
      functions for molecules containing heavy atoms. The efficiency of this new
      implementation is demonstrated in a detailed study of the spectroscopic
      properties of the gold dimer, and its scaling behavior has been tested by
      calculations of some closed-shell gold clusters (Au2, Au3+, Au4, Au5+). The
      algorithm is found to scale as O(N3), just as it does in the nonrelativistic
      case, and represents a dramatic improvement in efficiency over the conventional
      approach in the calculation of the Coulomb matrix, with computation times that
      are reduced to less than 3% for Au2 and up to 1% in the case of Au5+.

PMID- 16599660
TI  - Towards a spin-adapted coupled-cluster theory for high-spin open-shell states.
AB  - A spin-adapted coupled-cluster (SA-CC) scheme based on the additional
      consideration of spin constraints is proposed for the quantum chemical treatment
      of high-spin open-shell cases. Its computational feasibility is demonstrated via
      a pilot implementation within the singles and doubles approximation. Test
      calculations indicate that the suggested SA-CC scheme provides results of similar
      accuracy as the more traditional schemes without spin adaptation.

PMID- 16599661
TI  - Computation of methodology-independent ionic solvation free energies from
      molecular simulations. I. The electrostatic potential in molecular liquids.
AB  - The computation of ionic solvation free energies from atomistic simulations is a
      surprisingly difficult problem that has found no satisfactory solution for more
      than 15 years. The reason is that the charging free energies evaluated from such
      simulations are affected by very large errors. One of these is related to the
      choice of a specific convention for summing up the contributions of solvent
      charges to the electrostatic potential in the ionic cavity, namely, on the basis
      of point charges within entire solvent molecules (M scheme) or on the basis of
      individual point charges (P scheme). The use of an inappropriate convention may
      lead to a charge-independent offset in the calculated potential, which depends on
      the details of the summation scheme, on the quadrupole-moment trace of the
      solvent molecule, and on the approximate form used to represent electrostatic
      interactions in the system. However, whether the M or P scheme (if any)
      represents the appropriate convention is still a matter of on-going debate. The
      goal of the present article is to settle this long-standing controversy by
      carefully analyzing (both analytically and numerically) the properties of the
      electrostatic potential in molecular liquids (and inside cavities within them).
      Restricting the discussion to real liquids of "spherical" solvent molecules
      (represented by a classical solvent model with a single van der Waals interaction
      site), it is concluded that (i) for Coulombic (or straight-cutoff truncated)
      electrostatic interactions, the M scheme is the appropriate way of calculating
      the electrostatic potential; (ii) for non-Coulombic interactions deriving from a
      continuously differentiable function, both M and P schemes generally deliver an
      incorrect result (for which an analytical correction must be applied); and (iii)
      finite-temperature effects, including intermolecular orientation correlations and
      a preferential orientational structure in the neighborhood of a liquid-vacuum
      interface, must be taken into account. Applications of these results to the
      computation methodology-independent ionic solvation free energies from molecular
      simulations will be the scope of a forthcoming article.

PMID- 16599662
TI  - Grid-based Thomas-Fermi-Amaldi equation with the molecular cusp condition.
AB  - First, the Thomas-Fermi-Amaldi (TFA) equation was formulated with a newly derived
      condition to remove the singularities at the nuclei, which coincided with the
      molecular cusp condition. Next, the collocation method was applied to the TFA
      equation using the grid-based density functional theory. In this paper, the
      electron densities and the radial probabilities for specific atoms (He, Be, Ne,
      Mg, Ar, Ca) were found to agree with those from the Thomas-Fermi-Dirac (TFD)
      method. Total energies for specific atoms (He, Ne, Ar, Kr, Xe, Rn) and molecules
      (H2,CH4) were also found to be close to those from the Hartree-Fock method using
      the Pople basis set 6-311G relative to the TFD method. In addition, the
      computational expense to determine the electron density and its corresponding
      energy for a large scale structure, such as a carbon nanotube, is shown to be
      much more efficient compared to the conventional Hartree-Fock method using the 6
      31G Pople basis set.

PMID- 16599664
TI  - On the characterization of three state conical intersections: a quasianalytic
      theory using a group homomorphism approach.
AB  - In this work, degenerate perturbation theory through second order is used to
      characterize the vicinity of a three state conical intersection. This report
      extends our recent demonstration that it is possible to describe the branching
      space (in which the degeneracy is lifted linearly) and seam space (in which the
      degeneracy is preserved) in the vicinity of a two state conical intersection
      using second order perturbation theory. The general analysis developed here is
      based on a group homomorphism approach. Second order perturbation theory, in
      conjunction with high quality ab initio electronic structure data, produces an
      approximately diabatic Hamiltonian whose eigenenergies and eigenstates can
      accurately describe the three adiabatic potential energy surfaces, the interstate
      derivative couplings, and the branching and seam spaces in their full
      dimensionality. The application of this approach to the minimum energy three
      state conical intersection of the pyrazolyl radical demonstrates the potential of
      this method. A Hamiltonian comprised of the ten characteristic (linear)
      parameters and over 300 second order parameters is constructed to describe the
      branching space associated with a point of conical intersection. The second order
      parameters are determined using data at only 30 points. In the vicinity of the
      conical intersection the energy and derivative couplings are well reproduced and
      the singularity in the derivative coupling is analyzed.

PMID- 16599663
TI  - Development of a lattice-sum method emulating nonperiodic boundary conditions for
      the treatment of electrostatic interactions in molecular simulations: a continuum
      electrostatics study.
AB  - Artifacts induced by the application of periodic boundary conditions and lattice
      sum methods in explicit-solvent simulations of (bio-)molecular systems are
      nowadays a major concern in the computer-simulation community. The present
      article reports a first step toward the design of a modified lattice-sum
      algorithm emulating nonperiodic boundary conditions, and therefore exempt of such
      periodicity-induced artifacts. This result is achieved here in the (more simple)
      context of continuum electrostatics. It is shown that an appropriate modification
      of the periodic Poisson equation and of its boundary conditions leads to a
      continuum-electrostatics scheme, which, although applied under periodic boundary
      conditions, exactly mimics the nonperiodic situation. The possible extension of
      this scheme to explicit-solvent simulations is outlined and its practical
      implementation will be described in more details in a forthcoming article.

PMID- 16599665
TI  - Counterdiabatic suppression of background state population in resonance leaking
      by controlling intermediate branching.
AB  - The counterdiabatic principle [M. Demirplak and S. A. Rice, J. Phys. Chem. A 107,
      9937 (2003)] is used in a pragmatic way to formulate a practical control strategy
      for perturbed population transfer. Interpreting the appearance of population in
      undesirable intruder or background states as phenomenological consequences of
      diabatic perturbations, such branching is suppressed as soon as it arises. By
      invoking a penalty term that is sensitive to any transitional population in
      undesirable levels, a correction field is created which effectively prevents
      diabatic behavior. This strategy is applied to the control of background state
      population in multiphoton excitations. For a model five-level system we show that
      leaking of a resonant three-photon transition to a background state can readily
      be suppressed by simple correction fields obtained from our intermediate
      branching driven implementation of counterdiabatic control.

PMID- 16599666
TI  - Molecular-dynamics evaluation of fluid-phase equilibrium properties by a novel
      free-energy perturbation approach: application to gas solubility and vapor
      pressure of liquid hexane.
AB  - A novel free-energy perturbation method is developed for the computation of the
      free energy of transferring a molecule between fluid phases. The methodology
      consists in drawing a free-energy profile of the target molecule moving across a
      binary-phase structure built in the computer. The novelty of the method lies in
      the difference of the definition of the free-energy profile from the common
      definition. As an important element of the method, the process of making a
      correction to the transfer free energy with respect to the cutoff of
      intermolecular forces is elucidated. In order to examine the performance of the
      method in the application to fluid-phase equilibrium properties, molecular
      dynamics computations are carried out for the evaluation of gas solubility and
      vapor pressure of liquid n-hexane at 298.15 K. The gas species treated are
      methane, ethane, propane, and n-butane, with the gas solubility expressed as
      Henry's constant. It is shown that the method works fine and calculated results
      are generally in good agreement with experiments. It is found that the cutoff
      correction is strikingly large, constituting a dominant part of the calculated
      transfer free energy at the cutoff of 8 A.

PMID- 16599667
TI  - Assessing a new nonempirical density functional: difficulties in treating pi
      conjugation effects.
AB  - The reliability of the Tao-Perdew-Staroverov-Scuseria (TPSS) exchange-correlation
      functional for the description of conjugation effects in model pi-conjugated
      systems has been thoroughly assessed through the calculation of torsion energy
      profiles. The functional reproduces qualitatively the shape of torsional
      potentials but, interestingly, the mixing of TPSS and exact exchange governs the
      quantitative results: thus, well-defined hybrid extensions of the functional are
      consistently employed to improve the results. The hybrid approaches led to more
      accurate descriptions of conjugation effects but, however, the finest performance
      along the whole range of dihedral angles was obtained by a customized mixing of
      pure or hybrid TPSS functionals and wave function methods in a multicoefficient
      fashion. Despite the successful construction of this nonempirical functional,
      higher rungs of the ladder of methods in which TPSS is based are hoped to reduce
      the errors with respect to reference data for pi-conjugated systems.

PMID- 16599668
TI  - An optical-optical double resonance probe of the lowest triplet state of jet
      cooled thiophosgene: rovibronic structures and electronic relaxation.
AB  - The vibrational structure, rotational structure, and electronic relaxation of the
      "dark" T1 3A2(n,pi*) state of jet-cooled thiophosgene have been investigated by
      two-color S2<--T1<--S0 optical-optical double resonance (OODR) spectroscopy,
      which monitors the S2-->S0 fluorescence generated by S2<--T1 excitation. This
      method is capable of isolating the T1 vibrational structure into a1, b1, and b2
      symmetry blocks. The fluorescence-detected vibrational structure of the Tz spin
      state of T1 shows that the CS stretching frequency as well as the barrier height
      for pyramidal deformation are significantly greater in the 3A2(n,pi*) state than
      in the corresponding 1A2(n,pi*) state. The differing vibrational parameters of
      the T1 thiophosgene relative to the S1 thiophosgene can be attributed to the
      motions of unpaired electrons that are better correlated when they are in the
      excited singlet state than when they are in the triplet state of same electron
      configuration. A set of T1 structural parameters and the information concerning
      the T1 spin states have been obtained from least-square fittings of the
      rotationally resolved T1<--S0 excitation spectrum. The nearly degenerate mid R:x
      and mid R:y spin states are well removed from mid R:z spin component, indicating
      that T1 thiophosgene is a good example of case (ab) coupling. The decay of the
      mid R:z spin state of T1 thiophosgene, obtained from time-resolved S2<--T1<--S0
      OODR experiment, is characteristic of strong-coupling intermediate-case decay in
      which an initial rapid decay is followed by recurrences and/or a long-lived
      quasiexponential decay.

PMID- 16599669
TI  - A study of the ground state of manganese dimer using quasidegenerate perturbation
      theory.
AB  - We study the electronic structure of the ground state of the manganese dimer
      using the state-averaged complete active space self-consistent field method,
      followed by second-order quasidegenerate perturbation theory. Overall potential
      energy curves are calculated for the 1Sigmag+, 11Sigmau+, and 11Piu states, which
      are candidates for the ground state. Of these states, the 1Sigmag+ state has the
      lowest energy and we therefore identify it as the ground state. We find values of
      3.29 A, 0.14 eV, and 53.46 cm(-1) for the bond length, dissociation energy, and
      vibrational frequency, in good agreement with the observed values of 3.4 A, 0.1
      eV, and 68.1 cm(-1) in rare-gas matrices. These values show that the manganese
      dimer is a van der Waals molecule with antiferromagnetic coupling.

PMID- 16599670
TI  - Theoretical investigation of two-photon absorption allowed excited states in
      symmetrically substituted diacetylenes by ab initio molecular-orbital method.
AB  - Symmetrically substituted diacetylene compounds, which shows large two-photon
      absorption (TPA) cross sections, have been theoretically investigated by the ab
      initio molecular-orbital method employing several theoretical models including
      the configuration interaction with single excitation (CIS), random phase
      approximation (RPA), and time-dependent density-functional theory (TDDFT)
      methods. The calculated excited energies are overestimated by CIS or RPA, whereas
      underestimated by TDDFT with the B3LYP parametrization for both one-photon
      absorption (OPA) and TPA allowed states. The lowest OPA state is well described
      by the highest occupied molecular orbital (HOMO)-lowest unoccupied molecular
      orbital (LUMO) transition. On the other hand, lower TPA allowed states can be
      represented as the superposition of the HOMO-LUMO+1 and HOMO-1-LUMO transitions,
      giving rise to two TPA allowed states. The absorption intensity for the lower TPA
      state of the diacetylenes molecules is discussed in terms of the alternancy
      symmetry and its breaking. The symmetry property is differently manifested for
      neutral and dicationic diacetylenes. Introduction of charges breaks the
      alternancy symmetry, which gives rise to an increase in the TPA cross sections at
      the lower frequency. The upper TPA state is calculated to show huge TPA cross
      sections, which reproduces the enhancement of the TPA cross section
      experimentally observed for one of the diacetylenes at the higher-frequency
      region. The enhancement is discussed employing an index defined as the ratio of
      the transition polarizability and its static limit, which represents the degree
      of influence of one-photon resonance on the TPA intensity. The huge TPA cross
      sections are found to be due to a near-resonance effect. The present theoretical
      calculation approves the previously proposed assumption based on the four-state
      (dual three-state) model, which consists of the ground, one OPA allowed, and two
      TPA allowed states.

PMID- 16599671
TI  - How strong is the interaction between a noble gas atom and a noble metal atom in
      the insertion compounds MNgF (M=Cu and Ag, and Ng=Ar, Kr, and Xe)?
AB  - Ab initio molecular orbital calculations have been carried out to investigate the
      structure and the stability of noble gas insertion compounds of the type MNgF
      (M=Cu and Ag, and Ng=Ar, Kr, and Xe) through second order Moller-Plesset
      perturbation method. All the species are found to have a linear structure with a
      noble gas-noble metal bond, the distance of which is closer to the respective
      covalent bond length in comparison with the relevant van der Waals limit. The
      dissociation energies corresponding to the lowest energy fragmentation products,
      MF+Ng, have been found to be in the range of -231 to -398 kJ/mol. The respective
      barrier heights pertinent to the bent transition states (M-Ng-F bending mode) are
      quite high for the CuXeF and AgXeF species, although for the Ar and Kr containing
      species the same are rather low. Nevertheless the M-Ng bond length in MNgF
      compounds reported here is the smallest M-Ng bond ever predicted through any
      experimental or theoretical investigation, indicating strongest M-Ng interaction.
      All these species (except AgArF) are found to be metastable in their respective
      potential energy surface, and the dissociation energies corresponding to the
      M+Ng+F fragments have been calculated to be 30.1-155.3 kJ/mol. Indeed, in the
      present work we have demonstrated that the noble metal-noble gas interaction
      strength in MNgF species (with M=Cu and Ag, and Ng=Kr and Xe) is much stronger
      than that in NgMF systems. Bader's [Atoms in molecules-A Quantum Theory (Oxford
      University Press, Oxford, 1990)] topological theory of atoms in molecules (AIM)
      has been employed to explore the nature of interactions involved in these
      systems. Geometric as well as energetic considerations along with AIM results
      suggest a partial covalent nature of M-Ng bonds in these systems. The present
      results strengthen our earlier work and further support the proposition on the
      possibility of experimental identification of this new class of insertion
      compounds of noble gas atoms containing noble gas-noble metal bond.

PMID- 16599672
TI  - On the structure and chemical bonding of Si6(2-) and Si6(2-) in NaSi6(-) upon Na+
      coordination.
AB  - Photoelectron spectroscopy was combined with ab initio calculations to elucidate
      the structure and bonding in Si6 2- and NaSi6 -. Well-resolved electronic
      transitions were observed in the photoelectron spectra of Si6 - and NaSi6 - at
      three photon energies (355, 266, and 193 nm). The spectra of NaSi6 - were
      observed to be similar to those of Si6 - except that the electron binding
      energies of the former are lower, suggesting that the Si6 motif in NaSi6 - is
      structurally and electronically similar to that in Si6 -. The electron affinities
      of Si6 and NaSi6 were measured fairly accurately to be 2.23+/-0.03 eV and 1.80+/
      0.05 eV, respectively. Global minimum structure searches for Si6 2- and NaSi6 -
      were performed using gradient embedded genetic algorithm followed by B3LYP, MP2,
      and CCSDT calculations. Vertical electron detachment energies were calculated for
      the lowest Si6 - and NaSi6 - structures at the CCSD(T)/6-311+G(2df), ROVGF/6
      311+G(2df), UOVGF/6-311+G(2d), and time-dependent B3LYP/6-311+G(2df) levels of
      theory. Experimental vertical detachment energies were used to verify the global
      minimum structure for NaSi6 -. Though the octahedral Si6 2-, analogous to the
      closo form of borane B6H6 2-, is the most stable form for the bare hexasilicon
      dianion, it is not the kernel for the NaSi6 - global minimum. The most stable
      isomer of NaSi6 - is based on a Si6 2- motif, which is distorted into C2v
      symmetry similar to the ground state structure of Si6 -. The octahedral Si6 2-
      coordinated by a Na+ is a low-lying isomer and was also observed experimentally.
      The chemical bonding in Si6 2- and NaSi6 - was understood using natural bond
      orbital, molecular orbital, and electron localization function analyses.

PMID- 16599673
TI  - Potential energy surface, kinetics, and dynamics study of the Cl+CH4-->HCl+CH3
      reaction.
AB  - A modified and recalibrated potential energy surface for the gas-phase Cl+CH4-
      >HCl+CH3 reaction is reported and tested. It is completely symmetric with respect
      to the permutation of the four methane hydrogen atoms and is calibrated with
      respect to updated experimental and theoretical stationary point properties and
      experimental forward thermal rate constants. From the kinetics point of view, the
      forward and reverse thermal rate constants and the activation energies were
      calculated using the variational transition-state theory with semiclassical
      transmission coefficients over a wide temperature range of 150-2500 K. The
      theoretical results reproduce the available experimental data, with a small
      curvature of the Arrhenius plot which indicates the role of tunneling in this
      hydrogen abstraction reaction. A dynamics study was also performed on this PES
      using quasiclassical trajectory (QCT) calculations, including corrections to
      avoid zero-point energy leakage along the trajectories. First, we found a
      noticeable internal energy in the coproduct methyl radical, both in the ground
      state [CH4 (v=0)] and vibrationally excited [CH4 (v=1)] reactions. This CH3
      internal energy was directly precluded in some experiments or oversimplified in
      previous theoretical studies using pseudotriatomic models. Second, our QCT
      calculations give HCl rotational distributions slightly hotter than those in
      experiment, but correctly describing the experimental trend of decreasing the HCl
      product rotation excitation in going from HCl (v'=0) to HCl (v'=1) for the CH4
      (v=1) reaction. Third, the state specific scattering distributions present a
      reasonable agreement with experiment, although they tend to make the reaction
      more forward and backward scattered than found experimentally probably because of
      the hotter rotational distribution and the deficiencies of the QCT methods.

PMID- 16599674
TI  - Nonadiabatic dynamics in the photodissociation of ICH2CN at 266 and 304 nm
      studied by the velocity map imaging.
AB  - Photodissociation dynamics of iodoacetonitrile (ICH2CN) have been investigated at
      pump wavelengths of 266 and 304 nm using a photofragment ion image velocity
      mapping technique. At both wavelengths, the prompt C-I bond rupture takes place
      on the repulsive excited states to give I(2P3/2) and I*(2P1/2), and their speed
      and spatial distributions are simultaneously measured. The recoil anisotropy
      parameter (beta) at 266 nm is determined to be 1.10 and 1.60 for I and I*,
      respectively, while it is found to be much higher at 304 nm to give beta=1.70 and
      1.90 for I and I*, respectively. The branching ratios for I*I channels are
      measured to be 0.724 and 0.136 at 266 and 304 nm, respectively, giving insights
      on nonadiabatic transition phenomena and relative oscillator strengths of
      optically accessible transitions of ICH2CN. Accordingly, relative oscillator
      strengths of parallel/perpendicular transitions and nonadiabatic transitions
      among the excited states are quantitatively characterized. A large portion of the
      available energy (41%-48%) goes into the internal energy of the CH2CN fragment. A
      modified impulsive model in which the CH2CN fragment is assumed to be rigid
      predicts the energy disposal quite well. Delocalization of an unpaired electron
      of the CH2CN radical during the C-I bond cleavage, leading to a large structural
      change of the CH2CN moiety, may be responsible for internally hot fragments.

PMID- 16599675
TI  - Laser spectroscopic studies of several Rydberg states of MgO.
AB  - We report extensive spectroscopic measurements of rovibronic transitions from the
      MgO X 1Sigma+ ground state to the high-energy E 1Sigma+, F 1Pi1, and G 1Pi1
      Rydberg states. Perturbations in the E 1Sigma+ and G 1Pi1 states were observed.
      The Rydberg molecular orbital character of the three states is examined, given ab
      initio calculations by Thummel et al. [Chem. Phys. 129, 417 (1989)]. It is
      concluded that the E 1Sigma+ and G 1Pi1 states consist primarily of the MgO+ X
      2Pi ionic core, surrounded by 3ppi and 3psigma Rydberg electron clouds,
      respectively, and that the F 1Pi1 state consists primarily of the MgO+ A 2Sigma+
      ionic core surrounded by a 3ppi Rydberg electron cloud. Spectroscopic
      characterizations of some unassigned vibrational levels of analogous MgO 3Pi2
      states in this energy region are also reported.

PMID- 16599676
TI  - Direct calculation of coupled diabatic potential-energy surfaces for ammonia and
      mapping of a four-dimensional conical intersection seam.
AB  - We used multiconfiguration quasidegenerate perturbation theory and the fourfold
      way direct diabatization scheme to calculate ab initio potential-energy surfaces
      at 3600 nuclear geometries of NH3. The calculations yield the adiabatic and
      diabatic potential-energy surfaces for the ground and first electronically
      excited singlet states and also the diabatic coupling surfaces. The diabatic
      surfaces and coupling were fitted analytically to functional forms to obtain a
      permutationally invariant 2 x 2 diabatic potential-energy matrix. An analytic
      representation of the adiabatic potential-energy surfaces is then obtained by
      diagonalizing the diabatic potential-energy matrix. The analytic representation
      of the surfaces gives an analytic representation of the four-dimensional conical
      intersection seam which is discussed in detail.

PMID- 16599677
TI  - Vibrational Feshbach resonances in uracil and thymine.
AB  - Sharp peaks in the dissociative electron attachment (DEA) cross sections of
      uracil and thymine at energies below 3 eV are assigned to vibrational Feshbach
      resonances (VFRs) arising from coupling between the dipole bound state and the
      temporary anion state associated with occupation of the lowest sigma* orbital.
      Three distinct vibrational modes are identified, and their presence as VFRs is
      consistent with the amplitudes and bonding characteristics of the sigma* orbital
      wave function. A deconvolution method is also employed to yield higher effective
      energy resolution in the DEA spectra. The site dependence of DEA cross sections
      is evaluated using methyl substituted uracil and thymine to block H atom loss
      selectively. Implications for the broader issue of DNA damage are briefly
      discussed.

PMID- 16599679
TI  - Experimental and theoretical determination of the dipole-quadrupole and dipole
      octopole polarizabilities of the group IV tetrachlorides TiCl4, ZrCl4, and HfCl4.
AB  - The dipole-quadrupole and dipole-octopole polarizabilities A and E of TiCl4,
      ZrCl4, and HfCl4 have been determined from collision-induced light-scattering
      experiments. Our respective experimental results for /A/ are (165+/-10), (110+/
      30), and (140+/-20) e2a0 3Eh (-1), whereas /E/ is determined to be (675+/-125),
      (750+/-200), and (670+/-400) e2a0 4Eh (-1). Theory predicts values convincingly
      close to experiment, as A=(181.4+/-9.1), (167.6+/-8.4), and (139.8+/-7.0) e2a0
      3Eh (-1), and E=(-671+/-67), (-688+/-69), and (-574+/-57) e2a0 4Eh (-1). In
      addition our quantum chemical ab initio calculations give reliable values for the
      dipole polarizability alpha, as well as for the octopole and hexadecapole moments
      Omega and Phi for all three substances.

PMID- 16599678
TI  - Symmetry-dependent vibrational excitation in N 1s photoionization of N2:
      experiment and theory.
AB  - We have measured the vibrational structures of the N 1s photoelectron mainline
      and satellites of the gaseous N2 molecule with the resolution better than 75 meV.
      The gerade and ungerade symmetries of the core-ionized (mainline) states are
      resolved energetically, and symmetry-dependent angular distributions for the
      satellite emission allow us to resolve the Sigma and Pi symmetries of the shake
      up (satellite) states. Symmetry-adapted cluster-expansion configuration
      interaction calculations of the potential energy curves for the mainline and
      satellite states along with a Franck-Condon analysis well reproduce the observed
      vibrational excitation of the bands, illustrating that the theoretical
      calculations well predict the symmetry-dependent geometry relaxation effects. The
      energies of both mainline states and satellite states, as well as the splitting
      between the mainline gerade and ungerade states, are also well reproduced by the
      calculation: the splitting between the satellite gerade and ungerade states is
      calculated to be smaller than the experimental detection limit.

PMID- 16599680
TI  - Lower Rydberg series of methane: a combined coupled cluster linear response and
      molecular quantum defect orbital calculation.
AB  - Vertical excitation energies as well as related absolute photoabsorption
      oscillator strength data are very scarce in the literature for methane. In this
      study, we have characterized the three existing series of low-lying Rydberg
      states of CH4 by computing coupled cluster linear response (CCLR) vertical
      excitation energies together with oscillator strengths in the molecular-adapted
      quantum defect orbital formalism from a distorted Cs geometry selected on the
      basis of outer valence green function calculations. The present work provides a
      wide range of data of excitation energies and absolute oscillator strengths which
      correspond to the Rydberg series converging to the three lower ionization
      potential values of the distorted methane molecule, in energy regions for which
      experimentally measured data appear to be unavailable.

PMID- 16599681
TI  - Electron bridging dihydrogen bond in the imidazole-contained anion derivatives.
AB  - The large contact distance of electron bridging dihydrogen bond (EBDB), which is
      over 2.4 A, is the most prominent characteristic for the imidazole-contained
      anion derivatives. The elongation of N-H bond and the shortening of H...H
      distance can be observed upon hydration and hydrogenation. Transformation from
      EBDB to dissociative H2 is convenient upon sequential hydrogenation. The H...H
      distance decreases with the enhancement of the electronegativity of the heavy
      atom which contacts directly with one of these two hydrogen atoms. NMR shielding
      of the bonding N varies significantly upon hydration and hydrogenation. The spin
      spin coupling constants, 1J(H-H), is dominated predominantly by the paramagnetic
      spin-orbit and diamagnetic spin-orbit contributions instead of the Fermi-contact
      term. Enhancement of electronegativity of the heavy atom leads to the increase of
      1J(H-H) coupling constants. The stabilization is enhanced upon hydration
      predominantly for the formation of O-H...N H bond, while it is reversed upon
      hydrogenation for the cleavage of big pi bond, Pi5(6). Enhancement of the
      stability is demonstrated by the increase of stabilization energy and vertical
      electron detachment energy with the electronegativity of the heavy atom. The
      dominant contributions for the formation of such electron bridging dihydrogen
      bond are the high polarity of each fragment, large electron density between two
      fragments, and strong bonding interaction of the bridging electron with H(N)
      atoms. The H...H interaction can be formed by X-Hdelta+ and Hdelta- -Y polar
      molecules in Hdelta+...Hdelta- and Hdelta+...e...Hdelta+ of two forms.

PMID- 16599682
TI  - Theoretical study of the effects of F to Cl chemical substitution on the
      electronic structure and the luminescence properties of Cs2GeF6:Os4+ and
      Cs2ZrCl6:Os4+ materials.
AB  - It has been experimentally determined that Cs2ZrCl6:Os4+ shows luminescence and
      up-converted luminescence from the highest t(2g) (4) excited level 2 A1g(1A1g),
      whereas Cs2GeF6:Os4+ 2 A1g(1A1g) does not luminescence at all. Ab initio quantum
      chemical calculations on these materials are presented here and show that the
      variation of the energy gap between the t2g 4 and t2g 3 eg 1 manifolds with F to
      Cl chemical substitution is a key factor to interpret the experimental findings.
      This energy gap is calculated to be some 1500 cm(-1) (approximately 2nua1g) in
      the fluoride host, whereas it is about 3300 cm(-1) (approximately 9nua1g) in the
      chloride host. The calculated values for the ground state totally symmetric
      vibrational frequency nu(a1g) are 626 cm(-1) (Cs2GeF6:Os4+) and 355 cm(-1)
      (Cs2ZrCl6:Os4+), in good agreement with the available experimental data.
      Geometrical structure of (OsX6)2- clusters (X=F,Cl) embedded in Cs2GeF6 and
      Cs2ZrCl6 lattices is calculated as well. New assignments for some spectral
      features based in the results of our calculations are proposed.

PMID- 16599683
TI  - Infrared diode laser spectroscopy of jet-cooled NiCO, Ni(CO)3 (13CO), and
      Ni(CO3(C 18O).
AB  - Gas phase infrared spectroscopic investigations of the CO vibration of jet-cooled
      NiCO, Ni(CO)3(13CO), and Ni(CO)3(C18O) are reported. The spectra were obtained
      using a recently assembled pulsed-discharge slit-jet IR diode laser spectrometer.
      The rotationally resolved spectrum of NiCO was collected as it was formed in the
      discharge, while the spectra of Ni(CO)3(13CO) and Ni(CO)3(C18O) were recorded as
      they were destroyed. For NiCO, band origins of 2010.692 89(34) and 2010.645
      28(23) cm(-1) were measured, along with values of B0=0.151 094(7) and 0.149
      597(6) cm(-1) and B(1)=0.150 244(7) and 0.148 742(6) cm(-1) for 58NiCO and
      60NiCO, respectively. The B0 values for these isotopologs were used to determine
      the two bond lengths in NiCO, giving r0 (Ni-C)=1.641(40) A and r0 (C-O)=1.193(53)
      A, in agreement with recent microwave measurements. The constants determined for
      Ni(CO)3(13CO) were upsilon0=2022.075 753(95) cm(-1), B"=0.034 736(2) cm(-1), and
      B'=0.034 688(2) cm(-1). For Ni(CO)3(C18O), upsilon0=2021.936 83(18) cm(-1),
      B"=0.033 764(4) cm(-1), and B'=0.033 710(4) cm(-1) were obtained. From these
      rotational constants, bond lengths of r0 (Ni-C)=1.839+/-0.007 A and r0 (C
      O)=1.121+/-0.010 A were obtained. These values are discussed in relation to the
      bond lengths measured by electron and x-ray diffraction methods.

PMID- 16599684
TI  - Dynamics study of the reaction OH- + C2H2-->C2H- + H2O with crossed beams and
      density-functional theory calculations.
AB  - The proton transfer reaction between OH- and C2H2, the sole reactive process
      observed over the collision energy range from 0.37 to 1.40 eV, has been studied
      using the crossed beam technique and density-functional theory (DFT)
      calculations. The center of mass flux distributions of the product C2H- ions at
      three different energies are highly asymmetric, characteristic of a direct
      process occurring on a time scale much less than a rotational period of any
      transient intermediate. The maxima in the flux distributions correspond to
      product velocities and directions close to those of the precursor acetylene
      reactants. The reaction quantitatively transforms the entire exothermicity into
      internal excitation of the products, consistent with an energy release motif in
      which the proton is transferred early, in a configuration in which the forming
      bond is extended. This picture is supported by DFT calculations showing that the
      first electrostatically bound intermediate on the reaction pathway is the
      productlike C2H- H2O species. Most of the incremental translational energy in the
      two higher collision energy experiments appears in product translational energy,
      and provides an example of induced repulsive energy release characteristic of the
      heavy+light-heavy mass combination.

PMID- 16599685
TI  - Ab initio interpolated potential energy surface and classical reaction dynamics
      for HCO+ + H, HOC+ + H, and deuterated analogues.
AB  - Classical simulations of the reactions between HCO+/COH+ and hydrogen atoms, as
      well as their deuterated variants, have been carried out on an ab initio
      interpolated potential energy surface. The surface is constructed at the
      quadratic configuration interaction with single and double excitation level of ab
      initio calculation. At low energies we observe reaction channels associated with
      the isomerization of the cation, hydrogen/deuterium exchange, and the combination
      of isomerization with exchange. The HCO+/DCO+ ions only undergo exchange, and
      deuteration is more facile than the release of deuterium. The COH+/COD+ ions
      undergo isomerization or isomerization combined with exchange, the latter being
      the dominant reaction channel. Deuteration is again more facile than the release
      of deuterium, in combination with isomerization. These results are consistent
      with experimental measurements and with hypotheses on the deuteration of
      molecules in the interstellar medium.

PMID- 16599686
TI  - Electronic spectra of heteroatom-containing isoelectronic carbon chains C(2n)S
      and C2(n)Cl+ (n=1-5).
AB  - Structures and stabilities of carbon chains C(2n)S and C2(n)Cl+ (n=1-5) in their
      ground states have been investigated by the density functional theory and the
      coupled cluster approach using single and double substitutions. The complete
      active space self-consistent-field method has been used for geometry optimization
      of selected excited states in both series. Calculations show that both C(2n)S
      (n=1-5) and C2(n)Cl+ (n=3-5) have linear structures in the triplet ground state
      3Sigma-, while C2Cl+ and C4Cl+ have nonlinear structures in the ground state 3A".
      The vertical transition energies and emission energies by the
      multiconfigurational second-order perturbation theory in linear clusters C(2n)S
      and C2(n)Cl+ exhibit similar size dependences. In comparison with the available
      experimental observations, the predicted excitation energies for the allowed 2
      3Sigma- <--X 3Sigma- transitions have an accuracy of no more than 0.24 eV. Spin
      orbit coupling configuration interaction calculations indicate that the spin
      forbidden 2 1Sigma+<--X 3Sigma- transition in these species has an oscillator
      strength with the magnitude of 10(-4)-10(-5), and they may be observable
      experimentally.

PMID- 16599687
TI  - The ground state energy levels and molecular structure of jet-cooled HGeCl and
      DGeCl from single vibronic level emission spectroscopy.
AB  - Single vibronic level dispersed fluorescence spectra of jet-cooled HGeCl and
      DGeCl have been recorded by laser excitation of selected bands of the A 1A"-X 1A'
      electronic transition. Twenty-six ground state vibrational levels of HGeCl and 42
      of DGeCl were measured, assigned, and fitted to standard anharmonicity
      expressions, which allowed all the harmonic frequencies to be determined for both
      isotopomers. A normal coordinate least squares analysis obtained by fitting the
      harmonic frequencies yielded reliable values for five of the six force constants.
      The ground state effective rotational constants and force field data were
      combined to calculate average (rz) and approximate equilibrium (re z) structures,
      with re z(GeH)=1.586(1) A, re z(GeCl)=2.171(2) A, and the bond angle fixed at our
      CCSD(T)/aug-cc-pVTZ ab initio value of 93.9 degrees . Comparisons show that the
      derived bond lengths are consistent with those of the appropriate diatomic
      molecules in their ground electronic states and the bond angle is similar to that
      of germylene (GeH2). A Franck-Condon simulation of the vibrational intensities in
      the 0(0) (0) band emission spectrum of HGeCl using ab initio force field data
      shows good agreement with experiment, lending credence to the vibrational
      analysis of the observed spectra.

PMID- 16599688
TI  - Quantum mechanical investigations of the N(4S)+O2(X 3Sigmag -)-->NO(X 2Pi)+O(3P)
      reaction.
AB  - The reaction between energetic nitrogen atoms and oxygen molecules has received
      important attention in connection with nitric oxide chemistry in the lower
      thermosphere. We report time-independent quantum mechanical calculations of the
      N(4S)+O2-->NO+O reaction employing the X 2A' and a 4A' electronic potential
      energy surfaces of Sayos et al. [J. Chem. Phys. 117, 670 (2002)]. We confirm the
      production of highly vibrationally excited NO molecules, consistent with previous
      semiclassical and more recent time-dependent quantum wave packet studies.
      Calculations are carried out for total angular momentum quantum number J=0 and
      cross sections and rate coefficients are extracted using the J-shifting
      approximation. The results are in good agreement with available experimental and
      theoretical data.

PMID- 16599689
TI  - Electron attachment to POCl3: measurement and theoretical analysis of rate
      constants and branching ratios as a function of gas pressure and temperature,
      electron temperature, and electron energy.
AB  - Two experimental techniques, electron swarm and electron beam, have been applied
      to the problem of electron attachment to POCl3, with results indicating that
      there is a competition between dissociation of the resonant POCl3-* state and
      collisional stabilization of the parent anion. In the electron beam experiment at
      zero electron energy, the fragment ion POCl2- is the dominant ion product of
      attachment (96%), under single-collision conditions. Small amounts (approximately
      2% each) of POCl3- and Cl- were observed. POCl3- and POCl2- ion products were
      observed only at zero electron energy, but higher-energy resonances were recorded
      for POCl-, Cl-, and Cl2- ion products. In the electron swarm experiment, which
      was carried out in 0.4-7 Torr of He buffer gas, the parent anion branching ratio
      increased significantly with pressure and decreased with temperature. The
      electron attachment rate constant at 297 K was measured to be (2.5+/-0.6)x10(-7)
      cm3 s(-1), with ion products POCl2- (71%) and POCl3- (29%) in 1 Torr of He gas.
      The rate constant decreased as the electron temperature was increased above 1500
      K. Theory is developed for (a) the unimolecular dissociation of the nascent POCl3
      * and (b) a stepladder collisional stabilization mechanism using the average
      energy transferred per collision as a parameter. These ideas were then used to
      model the experimental data. The modeling showed that D0 o(Cl-POCl2-) and
      EA(POCl3) must be the same within +/-0.03 eV.

PMID- 16599690
TI  - A comparison of experimental and calculated spectra of HNO3 in the near-infrared
      using Fourier transform infrared spectroscopy and vibrational perturbation
      theory.
AB  - This work combines new laboratory studies of the near-infrared vibrational
      spectra of HNO3 with theoretical predictions of these spectra as a means to
      understand the properties of this molecule at energies well above the fundamental
      region. Trends in overtone and combination band energy levels and intensities are
      compiled and examined. The theoretical calculations are in excellent agreement
      with the observed frequencies and intensities of the transitions in this spectral
      region. The calculations also serve as a valuable aid for assigning many of the
      transitions. This work validates the ab initio generated potential energy surface
      for HNO3 by comparing vibrational perturbation theory calculations to
      experimental spectra focused on combination band and overtone absorptions.

PMID- 16599691
TI  - Structural and vibrational properties of solid nitromethane under high pressure
      by density functional theory.
AB  - The structural, vibrational, and electronic properties of solid nitromethane
      under hydrostatic pressure of up to 20 GPa have been studied using density
      functional theory. The changes of cell volume, the lattice constants, and the
      molecular geometry of solid nitromethane under hydrostatic loading are examined,
      and the bulk modulus B0 and its pressure derivative B0' are fitted from the
      volume-pressure relation. Our theoretical results are compared with available
      experiments. The change of electron band gap of nitromethane under high pressure
      is also discussed. Based on the optimized crystal structures, the vibrational
      frequencies for the internal and lattice modes of the nitromethane crystal at
      ambient and high pressures are computed, and the pressure-induced frequency
      shifts of these modes are discussed.

PMID- 16599692
TI  - A theoretical insight into the photophysics of psoralen.
AB  - Psoralen photophysics has been studied on quantum chemistry grounds using the
      multiconfigurational second-order perturbation method CASPT2. Absorption and
      emission spectra of the system have been rationalized by computing the energies
      and properties of the low-lying singlet and triplet excited states. The S1 pipi*
      state has been determined to be responsible of the lowest absorption and
      fluorescence bands and to initially carry the population in the photophysical
      processes related to the phototherapeutic properties of psoralen derivatives. The
      low-lying T1 pipi* state is, on the other hand, protagonist of the
      phosphorescence, and its prevalent role in the reactivity of psoralen is
      suggested to be related to the elongation of the pyrone ring C3-C4 bond, where
      the spin density is distributed on both carbon atoms. Analysis of energy gaps and
      spin-orbit coupling elements indicates that the efficient photophysical process
      leading to the population of the lowest triplet state does not take place at the
      Franck-Condon region but along the S1 relaxation path.

PMID- 16599693
TI  - Statistical mechanically averaged molecular properties of liquid water calculated
      using the combined coupled cluster/molecular dynamics method.
AB  - Liquid water is investigated theoretically using combined molecular dynamics (MD)
      simulations and accurate electronic structure methods. The statistical
      mechanically averaged molecular properties of liquid water are calculated using
      the combined coupled cluster/molecular mechanics (CC/MM) method for a large
      number of configurations generated from MD simulations. The method includes
      electron correlation effects at the coupled cluster singles and doubles level and
      the use of a large correlation consistent basis set. A polarizable force field
      has been used for the molecular dynamics part in both the CC/MM method and in the
      MD simulation. We describe how the methodology can be optimized with respect to
      computational costs while maintaining the quality of the results. Using the
      optimized method we study the energetic properties including the heat of
      vaporization and electronic excitation energies as well as electric dipole and
      quadrupole moments, the frequency dependent electric (dipole) polarizability, and
      electric-field-induced second harmonic generation first and second
      hyperpolarizabilities. Comparisons with experiments are performed where reliable
      data are available. Furthermore, we discuss the important issue on how to compare
      the calculated microscopic nonlocal properties to the experimental macroscopic
      measurements.

PMID- 16599695
TI  - Mean-field kinetic nucleation theory.
AB  - A new semiphenomenological model of homogeneous vapor-liquid nucleation is
      proposed in which the cluster kinetics follows the "kinetic approach to
      nucleation" and the thermodynamic part is based on the revised Fisher droplet
      model with the mean-field argument for the cluster configuration integral. The
      theory is nonperturbative in a cluster size and as such is valid for all clusters
      down to monomers. It contains two surface tensions: macroscopic (planar) and
      microscopic. The latter is a temperature dependent quantity related to the vapor
      compressibility factor at saturation. For Lennard-Jones fluids the microscopic
      surface tension possesses a universal behavior with the parameters found from the
      mean-field density functional calculations. The theory is verified against
      nucleation experiments for argon, nitrogen, water, and mercury, demonstrating
      very good agreement with experimental data. Classical nucleation theory fails to
      predict experimental results when a critical cluster becomes small.

PMID- 16599694
TI  - Impulsive solvent heating probed by picosecond x-ray diffraction.
AB  - The time-resolved diffraction signal from a laser-excited solution has three
      principal components: the solute-only term, the solute-solvent cross term, and
      the solvent-only term. The last term is very sensitive to the thermodynamic state
      of the bulk solvent, which may change during a chemical reaction due to energy
      transfer from light-absorbing solute molecules to the surrounding solvent
      molecules and the following relaxation to equilibrium with the environment around
      the scattering volume. The volume expansion coefficient alpha for a liquid is
      typically approximately 1 x 10(-3) K(-1), which is about 1000 times greater than
      for a solid. Hence solvent scattering is a very sensitive on-line thermometer.
      The decomposition of the scattered x-ray signal has so far been aided by
      molecular dynamics (MD) simulations, a method capable of simulating the solvent
      response as well as the solute term and solute/solvent cross terms for the data
      analysis. Here we present an experimental procedure, applicable to most hydrogen
      containing solvents, that directly measures the solvent response to a transient
      temperature rise. The overtone modes of OH stretching and CH3 asymmetric
      stretching in liquid methanol were excited by near-infrared femtosecond laser
      pulses at 1.5 and 1.7 microm and the ensuing hydrodynamics, induced by the
      transfer of heat from a subset of excited CH3OH* to the bulk and the subsequent
      thermal expansion, were probed by 100 ps x-ray pulses from a synchrotron. The
      time-resolved data allowed us to extract two key differentials: the change in the
      solvent diffraction from a temperature change at constant density, seen at a very
      short time delay approximately 100 ps, and a term from a change in density at
      constant temperature. The latter term becomes relevant at later times
      approximately 1 mus when the bulk of liquid expands to accommodate its new
      temperature at ambient pressure. These two terms are the principal building
      blocks in the hydrodynamic equation of state, and they are needed in a self
      consistent reconstruction of the solvent response during a chemical reaction. We
      compare the experimental solvent terms with those from MD simulations. The use of
      experimentally determined solvent differentials greatly improved the quality of
      global fits when applied to the time-resolved data for C2H4I2 dissolved in
      methanol.

PMID- 16599696
TI  - Three-dimensional-IR spectroscopy: beyond the two-point frequency fluctuation
      correlation function.
AB  - Three-dimensional-IR spectroscopy is proposed as a new spectroscopic technique
      that is sensitive to three-point frequency fluctuation correlation functions.
      This will be important when the statistics of the underlying stochastic process
      is non-Gaussian, and hence when the system does not follow the linear response
      hypothesis. Furthermore, a very general classification of nonlinear spectroscopy
      in terms of higher order frequency fluctuation correlation functions is
      introduced, according to which certain moments of a multidimensional spectrum are
      related to certain frequency fluctuation correlation functions. The
      classification is rigorous in the so-called inhomogeneous limit, but remains
      valid approximately also when motional narrowing becomes important. The work also
      puts a recent paper [J. Bredenbeck et al., Phys. Rev. Lett. 95, 083201 (2005)]
      onto solid theoretical grounds, where we have shown for the first time that fifth
      order spectroscopy--in this case transient two-dimensional spectroscopy--is
      indeed sensitive to the three-point frequency fluctuation correlation function.

PMID- 16599697
TI  - Real-time propagation time-dependent density functional theory study on the ring
      opening transformation of the photoexcited crystalline benzene.
AB  - Mechanism of the ring-opening transformation in the photoexcited crystalline
      benzene is investigated on the femtosecond scale by a computational method based
      on the real-time propagation (RTP) time-dependent density functional theory
      (TDDFT). The excited-state dynamics of the benzene molecule is also examined not
      only for the distinction between the intrinsic properties of molecule and the
      intermolecular interaction but for the first validation using the vibration
      frequencies for the RTP-TDDFT approach. It is found that the vibration
      frequencies of the excited and ground states in the molecule are well reproduced.
      This demonstrates that the present method of time evolution using the Suzuki
      Trotter-type split operator technique starting with the Franck-Condon state
      approximated by the occupation change of the Kohn-Sham orbitals is adequately
      accurate. For the crystalline benzene, we carried out the RTP-TDDFT simulations
      for two typical pressures. At both pressures, large swing of the C-H bonds and
      subsequent twist of the carbon ring occurs, leading to tetrahedral (sp3-like) C-H
      bonding. The nu4 and nu16 out-of-plane vibration modes of the benzene molecule
      are found mostly responsible for these motions, which is different from the
      mechanism proposed for the thermal ring-opening transformation occurring at
      higher pressure. Comparing the results between different pressures, we conclude
      that a certain increase of the intermolecular interaction is necessary to make
      seeds of the ring opening (e.g., radical site formation and breaking of the
      molecular character) even with the photoexcitation, while the hydrogen migration
      to fix them requires more free volume, which is consistent with the experimental
      observation that the transformation substantially proceeds on the decompression.

PMID- 16599698
TI  - Free energy landscape analysis of two-dimensional dipolar solvent model at
      temperatures below and above the rotational freezing point.
AB  - Ionic solvation in a polar solvent is modeled by a central charge surrounded by
      dipolar molecules posted on two-dimensional distorted lattice sites with simple
      rotational dynamics. Density of states is calculated by applying the Wang-Landau
      algorithm to both the energy and polarization states. The free energy landscapes
      of solvent molecules as a function of polarization are depicted to explore the
      competition between the thermal fluctuation and solvation energy. Without a
      central charge, for temperatures higher than the energy scale of the dipole
      dipole interactions, the energy landscape for the small polarization region
      exhibits a parabolic shape as predicted by Marcus [Rev. Mod. Phys. 65, 599
      (1993)] for electron transfer reaction, while there is an additional quartic
      contribution to the landscape for the large polarization region. When the
      temperature drops, the simulated free energy landscapes are no longer smooth due
      to the presence of multiple local minima arising from the frustrated interaction
      among the dipoles. The parabolic contribution becomes negligible and the energy
      landscape becomes quartic in shape. For a strong central charge, the energy
      landscape exhibits an asymmetric profile due to the contributions of linear and
      cubic terms that arise from the charge-dipole interactions.

PMID- 16599699
TI  - Ferroelectric domains in nitrobenzene-nitromethane solutions measured by hyper
      Rayleigh scattering.
AB  - Hyper-Rayleigh scattering (HRS) spectra were measured for liquid solutions of
      C6H5NO2 and CH3NO2 at T=300 K. The depolarized HRS spectra at small frequency
      shift are dominated by two components due to reorientation of the nitrobenzene
      molecules. One is a Lorentzian with spectral width nu1=0.16-0.45 cm(-1) and
      corresponding orientation relaxation time tau=33-12 ps. The second component is a
      narrow spike with spectral width <2 MHz and corresponding relaxation time tau>80
      ns, attributed to HRS from slowly relaxing ferroelectric domains. The dipole
      order parameter g0=0.053+/-0.005, saturation parameter p=0.9+/-0.1, and volume
      V=20+/-6 nm3 for these domains in nitromethane were determined from measurements
      of the nitrobenzene-concentration dependence of the intensity ratio for these two
      spectral components. Orientation of the 230 nitromethane molecules within each
      domain is inhomogenous but highly ordered.

PMID- 16599700
TI  - Methyl ethyl ketone+water+secondary butyl alcohol: a potential system for the
      exploration of a quadruple critical point.
AB  - We report preliminary experiments on the ternary-liquid mixture, methyl ethyl
      ketone (MEK)+water (W)+secondary butyl alcohol (sBA)--a promising system for the
      realization of the quadruple critical point (QCP). The unusual tunnel-shaped
      phase diagram shown by this system is characterized and visualized by us in the
      form of a prismatic phase diagram. Light-scattering experiments reveal that
      (MEK+W+sBA) shows near three-dimensional-Ising type of critical behavior near the
      lower critical solution temperatures, with the susceptibility exponent (gamma) in
      the range of 1.217< or =gamma< or =1.246. The correlation length amplitudes (xio)
      and the critical exponent (nu) of the correlation length (xi) are in the ranges
      of 3.536< or =xio < or =4.611 A and 0.619< or =nu< or =0.633, respectively. An
      analysis in terms of the effective susceptibility exponent (gammaeff) shows that
      the critical behavior is of the Ising type for MEK concentrations in the ranges
      of 0.1000< or =X< or =0.1250 and X> or =0.3000. But, for the intermediate range
      of 0.1750< or =X<0.3000, the system shows a tendency towards mean-field type of
      critical behavior. The advantages of the system (MEK+W+sBA) over the system (3
      methylpyridine+water+heavy water+potassium Iodide) for the realization of a QCP
      are outlined.

PMID- 16599701
TI  - Two-dimensional electronic spectra of symmetric dimers: Intermolecular coupling
      and conformational states.
AB  - We study the information content of two-dimensional (2D) electronic photon-echo
      (PE) spectra, with special emphasis on their potential to distinguish, for
      waiting times T=0, between different conformations of electronically coupled
      symmetric dimers. The analysis is performed on the basis of an analytical formula
      for the frequency-domain 2D PE signal. The symmetric dimers are modeled in terms
      of two identical, energy-degenerate, excitonically coupled pairs of electronic
      states in the site representation. The spectra of conformationally weighted
      ensembles, composed of either two or four dimers, are compared with their one
      dimensional linear absorption counterparts. In order to provide a realistic
      coupling pattern for the ensemble consisting of four dimers, excitonic couplings
      are estimated on the basis of optimized geometries and site-transition dipole
      moments, calculated by standard semiempirical methods for the bridged bithiophene
      structure 1,2-bithiophene-2-yl-ethane-1,2-dion (T2[CO]2). In the framework of our
      model, the highly readable 2D PE spectra can unambiguously identify spectral
      doublets, by relating peak heights and positions with mutual orientations of site
      localized transition dipoles.

PMID- 16599702
TI  - Multivariable kinetic theory of the first order phase transitions.
AB  - The problem of calculation of the steady state homogeneous nucleation rate in the
      multidimensional space of the variables describing a nucleus is considered.
      Within the framework of the theory proposed, expressions for the nucleation rate
      and the steady state distribution function of nuclei are derived. The expression
      for the nucleation rate is invariant with respect to the space dimensionality
      and, in particular, involves the result of the one-dimensional theory. The
      distribution function is obtained in the initial, physical variables. In
      connection with the analysis of restrictions on the current direction, the
      question of symmetry of the matrix of diffusivities is considered; on the basis
      of the detailed balance principle it is shown that this matrix is symmetric. The
      question of normalizing the equilibrium distribution functions is investigated
      and the physical picture of the equilibrium state is described. The procedure of
      reducing the multidimensional theory to the one-dimensional one is described.

PMID- 16599703
TI  - A method for dynamical characterization and high resolution 1H-NMR in dipolar
      coupled systems: application to liquid crystals.
AB  - We study the variation of 13C spectra as function of off-resonances in protons
      during decoupling, for continuous wave (cw) and small phase incremental
      alternation with 64-step (SPINAL-64) schemes in the liquid crystals 4-n-octyl-4'
      cyanobiphenyl (8CB) and 4-n-pentyl-4'-cyanobiphenyl (5CB). The self-decoupling
      mechanism induced by the strong homonuclear dipolar interactions provides a
      method to study the dynamics of the proton system through the 13C spectra. In the
      n-cyanobiphenyl (nCB) liquid crystals each nonquaternary carbon is coupled
      through dipolar interactions to more than one proton constituting a SI(N) group
      (with N> or =2). We extend the analytical treatment of the variation of the 13C
      spectrum with the off-resonance, described for SI groups, to SI(N) under cw
      decoupling. The dependence of the maxima of the 13C spectra as a function of
      proton off-resonance follows a Lorentzian line that depends on the rate of
      exchange among proton spin states. From the fitting parameters of this curve and
      the heteronuclear interaction measured in cross-polarization experiments, we
      extract dynamical information of the intramolecular 1H-1H interactions. In the
      case of SPINAL-64 we experimentally observe the same behavior. Under both kinds
      of decouplings, we characterize the chemical shift of the protons through the NMR
      spectra of carbons. The resulting values are in very good agreement with those
      obtained by other methods.

PMID- 16599704
TI  - Ultraviolet-visible-near infrared and mid-Fourier transform infrared
      spectroscopic studies of intermolecular interaction in cholesteryl oleyl
      carbonate in mesophases.
AB  - Ultraviolet-visible-near infrared (UV-Vis-NIR) and Fourier transform infrared
      (FTIR) spectroscopic studies are presented of molecular association between like
      molecules of cholesteryl oleyl carbonate, each containing suitable pi-donor
      (steroid ring C=C) and pi-acceptor (C-O single bonds united with a C=O bond to
      give a carbonate group) moieties. Frequency shifts and intensity enhancements of
      donor and acceptor oscillators appear to be governed by reduced mass, vibronic
      coupling constants, and a few other parameters such as relative change in force
      constants, etc. Donor-acceptor complex formation is characterized not only by the
      appearance of new bands in the mid-FTIR spectrum but also by the emergence of a
      new, intense electronic band centered at approximately 3700 cm(-1), the so-called
      charge-transfer band, in the UV-Vis-NIR spectrum. This band is strong in the
      smectic-A and solid phases, but progressively diminishes when temperature is
      raised to realize the upper end of the cholesteric phase and eventually the
      isotropic phase. Also, a new, small electronic band at approximately 360 nm, only
      seen in the entire thermal range of the cholesteric phase, is attributed to the
      Lifshitz-van der Waals interaction between pretransitional smectic-A domains
      existing in the cholesteric phase. It is argued that mesophases may owe their
      thermodynamic stability to both Lifshitz-van der Waals and vibronic coupling (or
      electron-phonon coupling in extended systems such as smectics and solids)
      interactions.

PMID- 16599705
TI  - Kirkwood-Buff integrals of aqueous alcohol binary mixtures.
AB  - The Kirkwood-Buff integrals of some binary aqueous alcohol mixtures are computed
      from the available vapor pressure measurements and compared with previous results
      as well as small angle neutron scattering experiments. The emphasis of the
      present report is on accuracy of the results that can be achieved by these two
      different types of measurements. This seems to be needed, mainly in view of the
      discrepancies between the various published results, as shown herein. It is
      argued that agreement in peak positions is more important than that in magnitude.
      In general, very good agreement is obtained by both methods, and sources of
      disagreements are discussed. The issue of the computer simulations of aqueous
      systems and the problematics related to correlations, microheterogeneity, and
      consequently the Kirkwood-Buff integrals are equally discussed herein.

PMID- 16599706
TI  - Nuclear quantum effects on an enzyme-catalyzed reaction with reaction path
      potential: proton transfer in triosephosphate isomerase.
AB  - Nuclear quantum mechanical effects have been examined for the proton transfer
      reaction catalyzed by triosephosphate isomerase, with the normal mode centroid
      path integral molecular dynamics based on the potential energy surface from the
      recently developed reaction path potential method. In the simulation, the primary
      and secondary hydrogens and the C and O atoms involving bond forming and bond
      breaking were treated quantum mechanically, while all other atoms were dealt
      classical mechanically. The quantum mechanical activation free energy and the
      primary kinetic isotope effects were examined. Because of the quantum mechanical
      effects in the proton transfer, the activation free energy was reduced by 2.3
      kcal/mol in comparison with the classical one, which accelerates the rate of
      proton transfer by a factor of 47.5. The primary kinetic isotope effects of kH/kD
      and kH/kT were estimated to be 4.65 and 9.97, respectively, which are in
      agreement with the experimental value of 4+/-0.3 and 9. The corresponding Swain
      Schadd exponent was predicted to be 3.01, less than the semiclassical limit value
      of 3.34, indicating that the quantum mechanical effects mainly arise from quantum
      vibrational motion rather than tunneling. The reaction path potential, in
      conjunction with the normal mode centroid molecular dynamics, is shown to be an
      efficient computational tool for investigating the quantum effects on enzymatic
      reactions involving proton transfer.

PMID- 16599707
TI  - Phase transitions of methane using molecular dynamics simulations.
AB  - Using a short ranged Lennard-Jones interaction and a long ranged electrostatic
      potential, CH4 under high pressure was modeled. Molecular dynamics simulations on
      small clusters (108 and 256 molecules) were used to explore the phase diagram.
      Regarding phase transitions at different temperatures, our numerical findings are
      consistent with experimental results to a great degree. In addition, the
      hysteresis effect is displayed in our results.

PMID- 16599708
TI  - Enol-keto tautomerism of aromatic photochromic Schiff base N,N'-bis(salicylidene)
      p-phenylenediamine: ground state equilibrium and excited state deactivation
      studied by solvatochromic measurements on ultrafast time scale.
AB  - A photochromic symmetric Schiff base, N,N'-bis(salicylidene)-p-phenylenediamine,
      is proposed as a probe for the study of solvent dependent enol-keto tautomerism
      in the ground and excited states. The ground state equilibrium between the enol
      keto tautomers is found to depend mainly not on polarity but on the proton
      donating ability of the solvent. Upon selective excitation of each of these
      tautomers, the same excited state of a keto tautomer is created: in enol, after
      the ultrafast excited state intramolecular proton transfer (ESIPT), reaction, and
      in keto tautomer, directly. Then some part (<30%) of excited molecules are
      transferred to the photochromic form in its ground state. The evidence of another
      ultrafast deactivation channel in the excited enol tautomer competing with ESIPT
      has been found. The solvent does not influence the ESIPT dynamics nor the
      efficiency of the creation of the photochrome.

PMID- 16599709
TI  - Density dependences of long-range fluctuations and short-range correlation
      lengths of CHF3 and CH2F2 in supercritical states.
AB  - Small-angle x-ray scattering (SAXS) measurements are carried out for
      supercritical polar fluorocarbons, CHF3 and CH2F2, along the isotherm of 1.04 in
      reduced temperatures with the density range from 0.3 to 1.5 in reduced units. A
      novel apparatus for determination of absorption factors of the sample fluids is
      used in the present measurements. The apparatus enables us to detect
      simultaneously the accurate factors during the observation of the SAXS signals.
      Long-range fluctuations such as density fluctuations and correlation lengths are
      evaluated from the obtained SAXS data. The reduced correlation lengths are
      obtained by normalization by each molecular size, in order to discuss the
      fluctuations independent of the difference of the individual molecular size. The
      density fluctuations and the reduced correlation lengths of CHF3 and CH2F2 are
      compared with those of CO2 and H2O. The results are as follows: H2O>CH2F2>CHF3
      approximately CO2 in the order of magnitude. The fluctuations of CH2F2 are
      significantly distinguishable from those of CHF3 and show intermediate aspect
      between H2O and a group of CO2 and CHF3. In addition, the short-range correlation
      lengths, i.e., the Ornstein-Zernike direct correlation lengths, are firstly
      discussed from both viewpoints of density and substance dependences. The reduced
      short-range correlation lengths normalized by individual molecular size are found
      to trace a universal curve as a function of the reduced density.

PMID- 16599710
TI  - Formation and relaxation of excited states in solution: a new time dependent
      polarizable continuum model based on time dependent density functional theory.
AB  - In this paper a novel approach to study the formation and relaxation of excited
      states in solution is presented within the integral equation formalism version of
      the polarizable continuum model. Such an approach uses the excited state relaxed
      density matrix to correct the time dependent density functional theory excitation
      energies and it introduces a state-specific solvent response, which can be
      further generalized within a time dependent formalism. This generalization is
      based on the use of a complex dielectric permittivity as a function of the
      frequency, epsilonomega. The approach is here presented in its theoretical
      formulation and applied to the various steps involved in the formation and
      relaxation of electronic excited states in solvated molecules. In particular,
      vertical excitations (and emissions), as well as time dependent Stokes shift and
      complete relaxation from vertical excited states back to ground state, can be
      obtained as different applications of the same theory. Numerical results on two
      molecular systems are reported to better illustrate the features of the model.

PMID- 16599711
TI  - Kinetic theory of binary nucleation based on a first passage time analysis.
AB  - The binary classical nucleation theory (BCNT) is based on the Gibbsian
      thermodynamics and applies the macroscopic concept of surface tension to nanosize
      clusters. This leads to severe inconsistencies and large discrepancies between
      theoretical predictions and experimental results regarding the nucleation rate.
      We present an alternative approach to the kinetics of binary nucleation which
      avoids the use of classical thermodynamics for clusters. The new approach is an
      extension to binary mixtures of the kinetic theory previously developed by
      Narsimhan and Ruckenstein and Ruckenstein and Nowakowski [J. Colloid Interface
      Sci. 128, 549 (1989); 137, 583 (1990)] for unary nucleation which is based on
      molecular interactions and in which the rate of emission of molecules from a
      cluster is determined via a mean first passage time analysis. This time is
      calculated by solving the single-molecule master equation for the probability
      distribution of a "surface" molecule moving in a potential field created by the
      cluster. The starting master equation is a Fokker-Planck equation for the
      probability distribution of a surface molecule with respect to its phase
      coordinates. Owing to the hierarchy of characteristic time scales in the
      evolution of the molecule, this equation can be reduced to the Smoluchowski
      equation for the distribution function involving only the spatial coordinates.
      The new theory is combined with density functional theory methods to determine
      the density profiles. This is essential for nucleation in binary systems
      particularly when one of the components is surface active. Knowing these
      profiles, one can determine the potential fields created by the cluster, its rate
      of emission of molecules, and the nucleation rate more accurately than by using
      the uniform density approximation. The new theory is illustrated by numerical
      calculations for a model binary mixture of Lennard-Jones monomers and rigidly
      bonded dimers of Lennard-Jones atoms. The amphiphilic character of the dimer
      component (i.e., its surface activity) is induced by the asymmetry in the
      interaction between a monomer and the two different sites of a dimer. The
      inconsistencies of the BCNT are avoided in the new theory.

PMID- 16599712
TI  - Surface and adsorption properties of alpha-tricalcium phosphate.
AB  - The interaction between bone replacement bioceramic materials and the body will
      take place at the surface of the material. In the present ab initio study, we
      have investigated surfaces of biologically important alpha-tricalcium phosphate
      (TCP) and adsorption of biological species including a Ca atom, an H2O molecule,
      and a SiO2 fragment on the surfaces. The results show that all these species
      adsorb on the surfaces. The Ca atoms are strongly chemisorbed with newly created
      Ca-O bonds similar to those in alpha-TCP bulk in bond length; a water molecule is
      adsorbed and in some cases also dissociated on the surfaces with the dissociative
      adsorption, the predominant process; a SiO2 fragment initially linear, strongly
      interacted with two oxygens of different PO4 groups and eventually forms a
      tetrahedral SiO4-like species which might be a precursor of the silicate present
      in Si-TCP materials.

PMID- 16599713
TI  - Quantum study of Eley-Rideal reaction and collision induced desorption of
      hydrogen atoms on a graphite surface. I. H-chemisorbed case.
AB  - Collision induced (CI) processes involving hydrogen atoms on a graphite surface
      are studied quantum mechanically within the rigid, flat surface approximation,
      using a time-dependent wave packet method. The Eley-Rideal (ER) reaction and
      collision induced desorption (CID) cross sections are obtained with the help of
      two propagations which use different sets of coordinates, a "product" and a
      "reagent" set. Several adsorbate-substrate initial states of the target H atom in
      the chemisorption well are considered, and CI processes are studied over a wide
      range of projectile energy. Results show that (i) the Eley-Rideal reaction is the
      major reactive outcome and (ii) CID cross sections do not exceed 4 A2 and present
      dynamic thresholds for low values of the target vibrational quantum number. ER
      cross sections show oscillations at high energies which cannot be reproduced by
      classical and quasiclassical trajectory calculations. They are related to the
      vibrational excitation of the reaction products, which is a rather steep
      decreasing function of the collision energy. This behavior causes a selective
      population of the low-lying vibrational states and allows the quantization of the
      product molecular states to manifest itself in a collisional observable. A peak
      structure in the CID cross section is also observed and is assigned to the
      selective population of metastable states of the transient molecular hydrogen.

PMID- 16599714
TI  - Quantum study of Eley-Rideal reaction and collision induced desorption of
      hydrogen atoms on a graphite surface. II. H-physisorbed case.
AB  - Following previous investigation of collision induced (CI) processes involving
      hydrogen atoms chemisorbed on graphite [R. Martinazzo and G. F. Tantardini, J.
      Chem. Phys. 124, 124702 (2006)], the case in which the target hydrogen atom is
      initially physisorbed on the surface is considered here. Several adsorbate
      substrate initial states of the target H atom in the physisorption well are
      considered, and CI processes are studied for projectile energies up to 1 eV.
      Results show that (i) Eley-Rideal cross sections at low collision energies may be
      larger than those found in the H-chemisorbed case but they rapidly decrease as
      the collision energy increases; (ii) product hydrogen molecules are vibrationally
      very excited; (iii) collision induced desorption cross sections rapidly increase,
      reaching saturation values greater than 10 A2; (iv) trapping of the incident
      atoms is found to be as efficient as the Eley-Rideal reaction at low energies and
      remains sizable (3-4 A2) at high energies. The latter adsorbate-induced trapping
      results mainly in formation of metastable hot hydrogen atoms, i.e., atoms with an
      excess energy channeled in the motion parallel to the surface. These atoms might
      contribute in explaining hydrogen formation on graphite.

PMID- 16599715
TI  - Dynamics of D2 released from the dissociation of D2O on a zirconium surface.
AB  - Hydrogen is efficiently released during water dissociation on zirconium (Zr),
      while even very rapid temperature programmed heating of a hydrogen covered Zr
      surface predominantly leads to dissolution (approximately 99% dissolution). To
      help resolve these apparently contradictory observations, we have studied the
      dynamics of water (D2O) dissociation on a crystalline Zr surface by probing the
      rotational and vibrational energy distributions of the D2 produced using resonant
      enhanced multiphoton ionization spectroscopy. The internal-state energy
      distribution of the D2 product was found to be rotationally cold and
      vibrationally hot with respect to the temperature of the surface. The rotational
      distribution shows slight deviations from Boltzmann's law, with a mean rotational
      temperature of 426 K while the surface is at 800 K. The population of the nu"=1
      vibration is at least four times higher than a 800 K temperature would allow,
      this corresponding to a vibrational temperature of 1100 K. Information on the
      translational energy of the D2 product have also been obtained by time-of-flight
      spectroscopy and it is found to be nearly thermally equilibrated with the surface
      temperature. Similar results were obtained from studies of D2 scattered from a
      clean Zr surface, and of D2 released by a slow thermal desorption process which
      involves dissolved hydrogen as the source. The reconciliation of the present
      results with those for thermal desorption of preadsorbed hydrogen implies a role
      for both surface and subsurface adsorption sites on the Zr surface and clearly
      demonstrates that at high temperatures, the release of D2 arises from the
      recombinative desorption of adsorbed hydrogen formed by the complete dissociation
      of D2O.

PMID- 16599716
TI  - Mobility of a particle immersed in a liquid film between two fluids.
AB  - The mobility of a particle immersed in a liquid film between two viscous fluids
      is calculated in point approximation. The mobility in the direction parallel to
      the film diverges logarithmically as the ratio of the sum of outside viscosities
      to the film viscosity tends to zero, as in the [Saffman-Delbruck, Proc. Natl.
      Acad. Sci. U.S.A. 72, 3111 (1975)] expression for the mobility of a particle
      embedded in a membrane. A simple expression for the limiting behavior is derived.
      For any values of the parameters the mobility tensor can be evaluated by
      numerical quadrature of two one-dimensional integrals.

PMID- 16599717
TI  - The formation of low-dimensional inorganic nanotube crystallites in carbon
      nanotubes.
AB  - The filling of carbon nanotubes, which vary in diameter and morphology, is
      directly observed by molecular dynamics computer simulation with a potential
      model which thermodynamically favors a four-coordinate bulk crystal structure.
      Inorganic nanotube (INT) structures form which are based on percolating hexagonal
      nets. For small carbon nanotube diameters the filling is shown to proceed via an
      "internal wetting" mechanism, which depends on the internal carbon nanotube area
      rather than the free volume. Both single- and double-walled INTs are predicted to
      form. The atomistic formation mechanisms are discussed and an intermediate
      structure identified. The INT structures, including the observed intermediate,
      are discussed by reference to a simple energy landscape. The formation energetics
      are discussed in terms of a simple analytical model which combines the INT strain
      energy and the tube-tube interactions. An effective phase diagram, which predicts
      the INT morphologies as a function of carbon nanotube diameter, is derived and
      discussed with respect to the analytical model.

PMID- 16599718
TI  - Calculation of solid-liquid interfacial free energy: a classical nucleation
      theory based approach.
AB  - We present a simple approach to calculate the solid-liquid interfacial free
      energy. This new method is based on the classical nucleation theory. Using the
      molecular dynamics simulation, we employ spherical crystal nuclei embedded in the
      supercooled liquids to create an ideal model of a homogeneous nucleation. The
      interfacial free energy is extracted by fitting the relation between the critical
      nucleus size and the reciprocal of the critical undercooling temperature. The
      orientationally averaged interfacial free energy is found to be 0.302+/-0.002 (in
      standard LJ unit). The temperature dependence of the interfacial free energy is
      also obtained in this work. We find that the interfacial free energy increases
      slightly with increasing temperature. The positive temperature coefficient of the
      interfacial free energy is in qualitative agreement with Spaepen's analysis
      [Solid State Phys. 47, FS181 (1994)] and Turnbull's empirical estimation [J.
      Appl. Phys. 21, 1022 (1950)].

PMID- 16599719
TI  - Theoretical study of ion desorption from poly-(methyl methacrylate) and poly
      (isopropenyl acetate) thin films through core excitation.
AB  - Site-specific chemical reactions following core excitation of poly-(methyl
      methacrylate) (PMMA) and poly-(isopropenyl acetate) (PiPAc) thin films were
      investigated. New x-ray absorption spectra of PMMA and PiPAc at the C and O K
      edges and theoretical spectra within the framework of density functional theory
      using model molecules were reported, and some new peak assignments were proposed
      for these spectra. Core-hole excited state molecular dynamics simulations were
      performed to discuss dissociation dynamics for the target systems, and some
      specific reaction mechanisms were discussed and explained theoretically; for
      example, the amount of CH3 ion fragments for PMMA was enhanced at the C and O K
      edges through the existence of the repulsive sigma*(O-CH3) excited state.

PMID- 16599720
TI  - Analytical electrostatics for biomolecules: beyond the generalized Born
      approximation.
AB  - The modeling and simulation of macromolecules in solution often benefits from
      fast analytical approximations for the electrostatic interactions. In our
      previous work [G. Sigalov et al., J. Chem. Phys. 122, 094511 (2005)], we proposed
      a method based on an approximate analytical solution of the linearized Poisson
      Boltzmann equation for a sphere. In the current work, we extend the method to
      biomolecules of arbitrary shape and provide computationally efficient algorithms
      for estimation of the parameters of the model. This approach, which we
      tentatively call ALPB here, is tested against the standard numerical Poisson
      Boltzmann (NPB) treatment on a set of 579 representative proteins, nucleic acids,
      and small peptides. The tests are performed across a wide range of solvent/solute
      dielectrics and at biologically relevant salt concentrations. Over the range of
      the solvent and solute parameters tested, the systematic deviation (from the NPB
      reference) of solvation energies computed by ALPB is 0.5-3.5 kcal/mol, which is 5
      50 times smaller than that of the conventional generalized Born approximation
      widely used in this context. At the same time, ALPB is equally computationally
      efficient. The new model is incorporated into the AMBER molecular modeling
      package and tested on small proteins.

PMID- 16599721
TI  - Lattice-Boltzmann simulation of the sedimentation of charged disks.
AB  - We report a series of lattice-Boltzmann simulations of the sedimentation velocity
      of charged disks. In these simulations, we explicitly account for the
      hydrodynamic and electrostatic forces on disks and on their electrical double
      layer. By comparing our results with those for spheres with equal surface and
      charge, we can clarify the effect of the particle shape on the sedimentation
      process. We find that disks and spheres exhibit a different dependence of the
      sedimentation velocity on the Debye screening length. An analysis of the behavior
      of highly charged disks (beyond the scope of the linearized Poisson-Boltzmann
      equation) shows that, in that regime, the charge dependence of the sedimentation
      velocity of disks and spheres is similar. This suggests that, at high charge, the
      effective hydrodynamic shape of the disks becomes more spherical.

PMID- 16599722
TI  - Conformational entropy of a pseudoknot polymer.
AB  - The thermodynamics and kinetics of ABAB pseudoknot formation owing to reversible
      intrachain reactions are investigated for a flexible polymer based on the off
      lattice Monte Carlo simulations. The polymer is made of N hard spheres tethered
      by inextensible bonds and consists of two reactive pairs AA and BB with binding
      energies -epsilon1 and -epsilon2, respectively, and three loop lengths (l1, l2,
      and l3). Although two intermediate states, loops A and B, may be formed, the
      folding path goes mainly through the intermediate loop whose free energy
      reduction associated with coil-to-loop crossover is greater. The conformational
      entropy loss is found to follow DeltaS=alpha ln N+G, where alpha approximately
      2.48 for coil-loop crossover and alpha approximately 2.43 for loop-pseudoknot
      crossover. The constant G depends on the three loop lengths and the two end-to
      reactive site lengths (L1 and L2). For a given total loop length, G is maximum
      when the three loop lengths are equal (l1=l2=l3). When l1=l3, the entropy loss is
      minimum if l2=0. However, the condition l1 not equal l3 makes G even smaller.
      This consequence indicates that asymmetry in loop lengths is thermodynamically
      favorable and this fact is consistent with observations of pseudoknotted RNA
      structures.

PMID- 16599723
TI  - Coherent exciton transport in dendrimers and continuous-time quantum walks.
AB  - We model coherent exciton transport in dendrimers by continuous-time quantum
      walks. For dendrimers up to the second generation the coherent transport shows
      perfect recurrences when the initial excitation starts at the central node. For
      larger dendrimers, the recurrence ceases to be perfect, a fact which resembles
      results for discrete quantum carpets. Moreover, depending on the initial
      excitation site, we find that the coherent transport to certain nodes of the
      dendrimer has a very low probability. When the initial excitation starts from the
      central node, the problem can be mapped onto a line which simplifies the
      computational effort. Furthermore, the long time average of the quantum
      mechanical transition probabilities between pairs of nodes shows characteristic
      patterns and allows us to classify the nodes into clusters with identical
      limiting probabilities. For the (space) average of the quantum mechanical
      probability to be still or to be again at the initial site, we obtain, based on
      the Cauchy-Schwarz inequality, a simple lower bound which depends only on the
      eigenvalue spectrum of the Hamiltonian.

PMID- 16599724
TI  - Colloidal phase transition driven by alternating electric field.
AB  - The transverse two-dimensional assembly of colloidal particles near an electrode
      surface subjected to ac polarization is studied by varying the frequency and
      field strength in the absence and presence of an added electrolyte. The variation
      of the translational and bond-orientational correlation functions with frequency
      suggests the existence of a hexatic phase in which the particles retain the
      remnants of the crystalline long-range orientational order, but has a liquidlike
      translational order. The electrohydrodynamic (EHD) flow is analyzed in the light
      of the existing theoretical models. The equilibrium distribution of particles is
      considered to be the resultant of the two opposing forces--Stoke's force due to
      EHD flow and the screened Coulomb interaction between the colloidal particles.
      Several features of the experimental results are discussed, such as the role
      played by the EHD flow in the particle aggregation, the dependence of the
      equilibrium interparticle separation on ionic strength, zeta potential, and
      particle size.

PMID- 16599725
TI  - A Monte Carlo study of the mesophases formed by polar bent-shaped molecules.
AB  - Liquid crystal phases formed by bent-shaped (or "banana") molecules are currently
      of great interest. Here we investigate by Monte Carlo computer simulations the
      phases formed by rigid banana molecules modeled combining three Gay-Berne sites
      and containing either one central or two lateral and transversal dipoles. We show
      that changing the dipole position and orientation has a profound effect on the
      mesophase stability and molecular organization. In particular, we find a uniaxial
      nematic phase only for off-center dipolar models and tilted phases only for the
      one with terminal dipoles.

PMID- 16599726
TI  - Gel to glass transition in simulation of a valence-limited colloidal system.
AB  - We numerically study a simple model for thermoreversible colloidal gelation in
      which particles can form reversible bonds with a predefined maximum number of
      neighbors. We focus on three and four maximally coordinated particles, since in
      these two cases the low valency makes it possible to probe, in equilibrium, slow
      dynamics down to very low temperatures T. By studying a large region of T and
      packing fraction phi we are able to estimate both the location of the liquid-gas
      phase separation spinodal and the locus of dynamic arrest, where the system is
      trapped in a disordered nonergodic state. We find that there are two distinct
      arrest lines for the system: a glass line at high packing fraction, and a gel
      line at low phi and T. The former is rather vertical (phi controlled), while the
      latter is rather horizontal (T controlled) in the phi-T plane. Dynamics on
      approaching the glass line along isotherms exhibit a power-law dependence on phi,
      while dynamics along isochores follow an activated (Arrhenius) dependence. The
      gel has clearly distinct properties from those of both a repulsive and an
      attractive glass. A gel to glass crossover occurs in a fairly narrow range in phi
      along low-T isotherms, seen most strikingly in the behavior of the nonergodicity
      factor. Interestingly, we detect the presence of anomalous dynamics, such as
      subdiffusive behavior for the mean squared displacement and logarithmic decay for
      the density correlation functions in the region where the gel dynamics interferes
      with the glass dynamics.

PMID- 16599727
TI  - Temperature dependence of solvation dynamics and anisotropy decay in a protein:
      ANS in bovine serum albumin.
AB  - Temperature dependence of solvation dynamics and fluorescence anisotropy decay of
      8-anilino-1-naphthalenesulfonate (ANS) bound to a protein, bovine serum albumin
      (BSA), are studied. Solvation dynamics of ANS bound to BSA displays a component
      (300 ps) which is independent of temperature in the range of 278-318 K and a long
      component which decreases from 5800 ps at 278 K to 3600 ps at 318 K. The
      temperature independent part is ascribed to a dynamic exchange of bound to free
      water with a low barrier. The temperature variation of the long component of
      solvation dynamics corresponds to an activation energy of 2.1 kcal mol(-1). The
      activation energy is ascribed to local segmental motion of the protein along with
      the associated water molecules and polar residues. The time scale of solvation
      dynamics is found to be very different from the time scale of anisotropy decay.
      The anisotropy decays are analyzed in terms of the wobbling motion of the probe
      (ANS) and the overall tumbling of the protein.

PMID- 16599728
TI  - Critical fluctuations of the micellar triethylene glycol monoheptyl ether-water
      system.
AB  - Using the equal volume criterion and also the pseudospinodal conception the
      critical demixing point of the triethylene glycol monoheptyl ether/water system
      (C7E3H2O) has been determined as Ycrit=0.1 and Tcrit=296.46 K (Y, mass fraction
      of surfactant). From density measurements the critical micelle concentration
      (cmc) followed as Ycmc=0.007 at 288.15 K and Ycmc=0.0066 at 298.15 K. The
      (static) shear viscosity etas and the mutual diffusion coefficient D of the
      C7E3H2O mixture of critical composition have been evaluated to yield their
      singular and background parts. From a combined treatment of both quantities the
      relaxation rate Gamma of order parameter fluctuations has been derived. Gamma
      follows power law with universal critical exponent and amplitude Gamma0=3.1 x
      10(9) s(-1). Broadband ultrasonic spectra of C7E3H2O mixtures exhibit a
      noncritical relaxation, reflecting the monomer exchange between micelles and the
      suspending phase, and a critical term due to concentration fluctuations. The
      former is subject to a relaxation time distribution that broadens when
      approaching the critical temperature. The latter can be well represented with the
      aid of the dynamic scaling model by Bhattacharjee and Ferrell (BF) [Phys. Rev. A.
      31, 1788 (1985)]. The half-attenuation frequency in the scaling function of the
      latter model is noticeably smaller (Omega12 (BF) approximately 1) than the
      theoretically predicted value Omega12 (BF)=2.1. This result has been taken as an
      indication of a coupling between the fluctuations in the local concentration and
      the kinetics of micelle formation, in correspondence with the idea of a
      fluctuation controlled monomer exchange [T. Telgmann and U. Kaatze, Langmuir 18,
      3068 (2002)].

PMID- 16599729
TI  - Alpha and beta relaxation dynamics of a fragile plastic crystal.
AB  - We present a thorough dielectric investigation of the relaxation dynamics of
      plastic crystalline Freon112, which exhibits freezing of the orientational
      degrees of freedom into a glassy crystal below 90 K. Among other plastic
      crystals, Freon112 stands out by being relatively fragile within Angell's
      [Relaxations in Complex Systems, edited by K. L. Ngai and G. B. Wright (NRL,
      Washington, DC, 1985), p. 3] classification scheme and by showing an unusually
      strong beta relaxation. Comparing the results to those on Freon112a, having only
      a single molecular conformation, points to the importance of the presence of two
      molecular conformations in Freon112 for the explanation of its unusual
      properties.

PMID- 16599730
TI  - A novel mesophase formed by top-shaped molecules in the bulk and unsupported thin
      films: a molecular dynamics study.
AB  - We have used molecular dynamics simulations to investigate the ordering of top
      shaped molecules in bulk phases and in unsupported thin films. Each rigid
      anisotropic molecule was composed of 11 Lennard-Jones interaction centers
      (beads). In an attempt to enhance the nematic stability in preference to smectic,
      the three central beads were assigned a larger Lennard-Jones diameter than the
      tail beads, giving the molecule a shape resembling a top. The molecular model was
      found to exhibit an unusual bulk mesophase with long-range orientational order
      and with molecular center-of-mass positions arranged in parallel interdigitated
      layers, with layer spacing smaller than half the length of the long axis of a
      molecule. However, despite the toplike molecular shape, no nematic phase was
      observed in the pressure range studied. Unsupported films of the isotropic liquid
      were cooled in order to locate a triple point between the novel mesophase, vapor,
      and isotropic liquid. At temperatures slightly above the triple point, enhanced
      surface ordering of molecules was found to occur in the unsupported film. At
      temperatures slightly below the triple point, the preferred molecular alignment
      in the unsupported film was parallel to the interface, in violation of arguments
      that have been proposed based on the relative enthalpies of various cleavage
      planes for close-packed structures.

PMID- 16599731
TI  - Self-recognition and aggregation between diblock (charged/neutral)
      polyelectrolytes by Monte Carlo simulations.
AB  - The self-recognition between oppositely charged polyelectrolyte-neutral diblock
      copolymers and aggregate formation is investigated by Monte Carlo simulations.
      Both matched lengths and charge numbers are critical conditions for self
      recognition. The optimum self-recognition occurs between oppositely charged
      chains with matched charged block lengths and charge numbers. The size of
      aggregates increases, as the total length and the ratio of charged to neutral
      beads become larger. Polyelectrolyte networks were observed in some cases
      containing unmatched chains. The molecular configurations of the entire chains
      and of the charged and neutral blocks as well as the radial distribution
      functions of the charged beads are also investigated.

PMID- 16599733
TI  - Chaotic and pseudochaotic attractors of perturbed fractional oscillator.
AB  - We consider a nonlinear oscillator of the Duffing type with fractional derivative
      of the order 1<alpha<2. In this system replacement of the regular derivative by
      the fractional one leads to decaying solutions. The main feature of the system is
      that decay is asymptotically the powerwise situation that appears in different
      applications. Perturbed by a periodic force, the system exhibits chaotic motion
      called fractional chaotic attractor (FCA). The FCA is compared to the "regular"
      chaotic attractor that exists in the periodically forced Duffing oscillator. The
      properties of the FCA are discussed and the "pseudochaotic" case is demonstrated
      numerically for the case of the "dying attractor." We call "pseudochaos" the case
      when the randomness exists with zero Lyapunov exponent, i.e., the dispersion of
      initially close trajectories is subexponential.

PMID- 16599732
TI  - Synchronization in uncertain complex networks.
AB  - We consider the problem of synchronization in uncertain generic complex networks.
      For generic complex networks with unknown dynamics of nodes and unknown coupling
      functions including uniform and nonuniform inner couplings, some simple linear
      feedback controllers with updated strengths are designed using the well-known
      LaSalle invariance principle. The state of an uncertain generic complex network
      can synchronize an arbitrary assigned state of an isolated node of the network.
      The famous Lorenz system is stimulated as the nodes of the complex networks with
      different topologies. We found that the star coupled and scale-free networks with
      nonuniform inner couplings can be in the state of synchronization if only a
      fraction of nodes are controlled.

PMID- 16599734
TI  - Evaluation of channel coding and decoding algorithms using discrete chaotic maps.
AB  - In this paper we address the design of channel encoding algorithms using one
      dimensional nonlinear chaotic maps starting from the desired invariant
      probability density function (pdf) of the data sent to the channel. We show that,
      with some simple changes, it is straightforward to make use of a known encoding
      framework based upon the Bernoulli shift map and adapt it readily to carry the
      information bit sequence produced by a binary source in a practical way. On the
      decoder side, we introduce four already known decoding algorithms and compare the
      resulting performance of the corresponding transmitters. The performance in terms
      of the bit error rate shows that the most important design clue is related not
      only to the pdf of the data produced by the chosen discrete map: the own dynamics
      of the maps is also of the highest importance and has to be taken into account
      when designing the whole transmitting and receiving system. We also show that a
      good performance in such systems needs the extensive use of all the evidence
      stored in the whole chaotic sequence.

PMID- 16599735
TI  - Transmitting a signal by amplitude modulation in a chaotic network.
AB  - We discuss the ability of a model of network with nonlinear units and chaotic
      dynamics to transmit signals, on the basis of a linear response theory developed
      by Ruelle [D. Ruelle, J. Stat. Phys. 95, 393 (1999)] for dissipative systems. We
      discuss in particular how the dynamics may interfere with the graph topology to
      produce an effective transmission network, whose topology depends on the signal,
      and cannot be directly read on the "wired" network. Then, we show examples where,
      with a suitable choice of the carrier frequency (resonance), one can transmit a
      signal from a node to another one by amplitude modulation, in spite of chaos.
      Also, we give an example where a signal, transmitted to any node via different
      paths, can only be recovered by a couple of specific nodes. This opens up the
      possibility for encoding data in a way such that the recovery of the signal
      requires the knowledge of the carrier frequency and can be performed only at some
      specific node.

PMID- 16599736
TI  - Global point dissipativity of neural networks with mixed time-varying delays.
AB  - By employing the Lyapunov method and some inequality techniques, the global point
      dissipativity is studied for neural networks with both discrete time-varying
      delays and distributed time-varying delays. Simple sufficient conditions are
      given for checking the global point dissipativity of neural networks with mixed
      time-varying delays. The proposed linear matrix inequality approach is
      computationally efficient as it can be solved numerically using standard
      commercial software. Illustrated examples are given to show the usefulness of the
      results in comparison with some existing results.

PMID- 16599737
TI  - Error criteria for cross validation in the context of chaotic time series
      prediction.
AB  - The prediction of a chaotic time series over a long horizon is commonly done by
      iterating one-step-ahead prediction. Prediction can be implemented using machine
      learning methods, such as radial basis function networks. Typically, cross
      validation is used to select prediction models based on mean squared error. The
      bias-variance dilemma dictates that there is an inevitable tradeoff between bias
      and variance. However, invariants of chaotic systems are unchanged by linear
      transformations; thus, the bias component may be irrelevant to model selection in
      the context of chaotic time series prediction. Hence, the use of error variance
      for model selection, instead of mean squared error, is examined. Clipping is
      introduced, as a simple way to stabilize iterated predictions. It is shown that
      using the error variance for model selection, in combination with clipping, may
      result in better models.

PMID- 16599738
TI  - Topology of music recommendation networks.
AB  - We study the topology of several music recommendation networks, which arise from
      relationships between artist, co-occurrence of songs in play lists or experts'
      recommendation. The analysis uncovers the emergence of complex network phenomena
      in these kinds of recommendation networks, built considering artists as nodes and
      their resemblance as links. We observe structural properties that provide some
      hints on navigation and possible optimizations on the design of music
      recommendation systems. Finally, the analysis derived from existing music
      knowledge sources provides a deeper understanding of the human music similarity
      perception.

PMID- 16599739
TI  - Testing statistical significance of multivariate time series analysis techniques
      for epileptic seizure prediction.
AB  - Nonlinear time series analysis techniques have been proposed to detect changes in
      the electroencephalography dynamics prior to epileptic seizures. Their
      applicability in practice to predict seizure onsets is hampered by the present
      lack of generally accepted standards to assess their performance. We propose an
      analytic approach to judge the prediction performance of multivariate seizure
      prediction methods. Statistical tests are introduced to assess patient individual
      results, taking into account that prediction methods are applied to multiple time
      series and several seizures. Their performance is illustrated utilizing a
      bivariate seizure prediction method based on synchronization theory.

PMID- 16599740
TI  - Stabilizing long-period orbits via symbolic dynamics in simple limiter
      controllers.
AB  - We present an efficient approach to determine the control parameter of simple
      limiter controllers by using symbolic dynamics of one-dimensional unimodal maps.
      By applying addition- and subtraction-symbol rules for generating an admissible
      periodic sequence, we deal with the smallest base problem of the digital tent
      map. The proposed solution is useful for minimizing the configuration of digital
      circuit designs for a given target sequence. With the use of the limiter
      controller, we show that one-dimensional unimodal maps may be robustly employed
      to generate the maximum-length shift-register sequences. For an arbitrary long
      Sarkovskii sequence, the control parameters are analytically given.

PMID- 16599741
TI  - Chaos in computer performance.
AB  - Modern computer microprocessors are composed of hundreds of millions of
      transistors that interact through intricate protocols. Their performance during
      program execution may be highly variable and present aperiodic oscillations. In
      this paper, we apply current nonlinear time series analysis techniques to the
      performances of modern microprocessors during the execution of prototypical
      programs. Our results present pieces of evidence strongly supporting that the
      high variability of the performance dynamics during the execution of several
      programs display low-dimensional deterministic chaos, with sensitivity to initial
      conditions comparable to textbook models. Taken together, these results show that
      the instantaneous performances of modern microprocessors constitute a complex (or
      at least complicated) system and would benefit from analysis with modern tools of
      nonlinear and complexity science.

PMID- 16599742
TI  - Numerical and experimental exploration of phase control of chaos.
AB  - A well-known method to suppress chaos in a periodically forced chaotic system is
      to add a harmonic perturbation. The phase control of chaos scheme uses the phase
      difference between a small added harmonic perturbation and the main driving to
      suppress chaos, leading the system to different periodic orbits. Using the
      Duffing oscillator as a paradigm, we present here an in-depth study of this
      technique. A thorough numerical exploration has been made focused in the
      important role played by the phase, from which new interesting patterns in
      parameter space have appeared. On the other hand, our novel experimental
      implementation of phase control in an electronic circuit confirms both the well
      known features of this method and the new ones detected numerically. All this may
      help in future implementations of phase control of chaos, which is globally
      confirmed here to be robust and easy to implement experimentally.

PMID- 16599743
TI  - Moving embedded lattice solitons.
AB  - It was recently proved that solitons embedded in the spectrum of linear waves may
      exist in discrete systems, and explicit solutions for isolated unstable embedded
      lattice solitons (ELS) of a differential-difference version of a higher-order
      nonlinear Schrodinger equation were found [Gonzalez-Perez-Sandi, Fujioka, and
      Malomed, Physica D 197, 86 (2004)]. The discovery of these ELS gives rise to
      relevant questions such as the following: (1) Are there continuous families of
      ELS? (2) Can ELS be stable? (3) Is it possible for ELS to move along the lattice?
      (4) How do ELS interact? The present work addresses these questions by showing
      that a novel equation (a discrete version of a complex modified Korteweg-de Vries
      equation that includes next-nearest-neighbor couplings) has a two-parameter
      continuous family of exact ELS. These solitons can move with arbitrary velocities
      across the lattice, and the numerical simulations demonstrate that these ELS are
      completely stable. Moreover, the numerical tests show that these ELS are robust
      enough to withstand collisions, and the result of a collision is only a shift in
      the positions of the solitons. The model may apply to the description of a Bose
      Einstein condensate with dipole-dipole interactions between the atoms, trapped in
      a deep optical-lattice potential.

PMID- 16599744
TI  - Synchronization and propagation of bursts in networks of coupled map neurons.
AB  - The present paper studies regular and complex spatiotemporal behaviors in
      networks of coupled map-based bursting oscillators. In-phase and antiphase
      synchronization of bursts are studied, explaining their underlying mechanisms in
      order to determine how network parameters separate them. Conditions for emergent
      bursting in the coupled system are derived from our analysis. In the region of
      emergence, patterns of chaotic transitions between synchronization and
      propagation of bursts are found. We show that they consist of transient standing
      and rotating waves induced by symmetry-breaking bifurcations, and can be viewed
      as a manifestation of the phenomenon of chaotic itinerancy.

PMID- 16599745
TI  - A study of the asymmetric Malkus waterwheel: the biased Lorenz equations.
AB  - In this work, the asymmetric case of the Malkus waterwheel is studied, where the
      water inflow to the system is biasing the system toward stable motion in one
      direction, like a Pelton wheel. The governing equations of this system, when
      expressed in Fourier space and decoupled to form a closed set, can be mapped into
      a four-dimensional space where they form a quasi-Lorenz system. This set of
      equations is analyzed in light of analogues of the Rayleigh Bernard convection
      and conclusions are drawn. The properties and behavior of the equations are
      studied and correlated to the physical model. Phase space behavior and linear
      stability analysis are used for this. Spectral analysis is used as a qualitative
      measure of chaos. Chaotic behavior is quantified through the calculation of the
      Lyapunov exponents and these are further correlated to the bifurcation diagrams
      for a conclusive analysis of the dynamical behavior of the system.

PMID- 16599746
TI  - Piecewise affine models of chaotic attractors: the Rossler and Lorenz systems.
AB  - This paper proposes a procedure by which it is possible to synthesize Rossler
      [Phys. Lett. A 57, 397-398 (1976)] and Lorenz [J. Atmos. Sci. 20, 130-141 (1963)]
      dynamics by means of only two affine linear systems and an abrupt switching law.
      Comparison of different (valid) switching laws suggests that parameters of such a
      law behave as codimension one bifurcation parameters that can be changed to
      produce various dynamical regimes equivalent to those observed with the original
      systems. Topological analysis is used to characterize the resulting attractors
      and to compare them with the original attractors. The paper provides guidelines
      that are helpful to synthesize other chaotic dynamics by means of switching
      affine linear systems.

PMID- 16599747
TI  - Geometric noise reduction for multivariate time series.
AB  - We propose an algorithm for the reduction of observational noise in chaotic
      multivariate time series. The algorithm is based on a maximum likelihood
      criterion, and its goal is to reduce the mean distance of the points of the
      cleaned time series to the attractor. We give evidence of the convergence of the
      empirical measure associated with the cleaned time series to the underlying
      invariant measure, implying the possibility to predict the long run behavior of
      the true dynamics.

PMID- 16599748
TI  - Soliton ratchets in homogeneous nonlinear Klein-Gordon systems.
AB  - We study in detail the ratchetlike dynamics of topological solitons in
      homogeneous nonlinear Klein-Gordon systems driven by a biharmonic force. By using
      a collective coordinate approach with two degrees of freedom, namely the center
      of the soliton, X(t), and its width, l(t), we show, first, that energy is
      inhomogeneously pumped into the system, generating as result a directed motion;
      and, second, that the breaking of the time shift symmetry gives rise to a
      resonance mechanism that takes place whenever the width l(t) oscillates with at
      least one frequency of the external ac force. In addition, we show that for the
      appearance of soliton ratchets, it is also necessary to break the time-reversal
      symmetry. We analyze in detail the effects of dissipation in the system,
      calculating the average velocity of the soliton as a function of the ac force and
      the damping. We find current reversal phenomena depending on the parameter choice
      and discuss the important role played by the phases of the ac force. Our
      analytical calculations are confirmed by numerical simulations of the full
      partial differential equations of the sine-Gordon and phi4 systems, which are
      seen to exhibit the same qualitative behavior. Our results show features similar
      to those obtained in recent experimental work on dissipation induced symmetry
      breaking.

PMID- 16599749
TI  - On the motion of a heavy rigid body in an ideal fluid with circulation.
AB  - We consider Chaplygin's equations [Izd. Akad. Nauk SSSR 3, 3 (1933)] describing
      the planar motion of a rigid body in an unbounded volume of an ideal fluid while
      circulation around the body is not zero. Hamiltonian structures and new
      integrable cases are revealed; certain remarkable partial solutions are found and
      their stability is examined. The nonintegrability of the system describing the
      motion of a body in the field of gravity is proved and the chaotic behavior of
      the system is illustrated.

PMID- 16599750
TI  - Q-S (complete or anticipated) synchronization backstepping scheme in a class of
      discrete-time chaotic (hyperchaotic) systems: a symbolic-numeric computation
      approach.
AB  - First, a type of Q-S (complete or anticipated) synchronization is defined in
      discrete-time dynamical systems. Second, based on backstepping design with a
      scalar controller, a systematic, concrete and automatic scheme is presented to
      investigate Q-S (complete or anticipated) synchronization between the discrete
      time drive system and response system with strict-feedback form. Finally, the
      proposed scheme is used to illustrate Q-S (complete or anticipated)
      synchronization between the two-dimensional discrete-time Lorenz system and Fold
      system, as well as the three-dimensional hyperchaotic discrete-time Rossler
      system and generalized discrete-time Rossler system. Moreover numerical
      simulations are used to verify the effectiveness of the proposed scheme. Our
      scheme can be also extended to investigate Q-S (complete or anticipated)
      synchronization between other discrete-time dynamical systems with strict
      feedback forms. With the aid of symbolic-numeric computation, the scheme can be
      performed to yield automatically the scalar controller and to verify its
      effectiveness in computer.

PMID- 16599751
TI  - Manifolds on the verge of a hyperbolicity breakdown.
AB  - We study numerically the disappearance of normally hyperbolic invariant tori in
      quasiperiodic systems and identify a scenario for their breakdown. In this
      scenario, the breakdown happens because two invariant directions of the
      transversal dynamics come close to each other, losing their regularity. On the
      other hand, the Lyapunov multipliers associated with the invariant directions
      remain more or less constant. We identify notable quantitative regularities in
      this scenario, namely that the minimum angle between the two invariant directions
      and the Lyapunov multipliers have power law dependence with the parameters. The
      exponents of the power laws seem to be universal.

PMID- 16599752
TI  - Implementation and synchronization of 3x3 grid scroll chaotic circuits with
      analog programmable devices.
AB  - The implementation of circuits with complex dynamics is a very challenging
      problem. In this paper we present a new chaotic circuit based on the dynamical
      equations introduced in IEEE Trans. Circuits Syst., I: Fundam. Theory Appl. 51,
      2476-2490 (2004). This circuit has been realized by using programmable analog
      devices, and, in particular, field programmable analog arrays have been used to
      implement a two-dimensional 3x3 grid scroll chaotic attractor. The implementation
      of complex dynamics with low cost circuits is very appealing; moreover, the
      implementation of the chaotic attractor discussed in this paper is not present in
      the literature. The experimental results including the synchronization between
      two chaotic circuits show complete agreement with the simulation results reported
      in IEEE Trans. Circuits Syst., I: Fundam. Theory Appl. 51, 2476-2490 (2004).

PMID- 16599753
TI  - A normal form for excitable media.
AB  - We present a normal form for traveling waves in one-dimensional excitable media
      in the form of a differential delay equation. The normal form is built around the
      well-known saddle-node bifurcation generically present in excitable media. Finite
      wavelength effects are captured by a delay. The normal form describes the
      behavior of single pulses in a periodic domain and also the richer behavior of
      wave trains. The normal form exhibits a symmetry preserving Hopf bifurcation
      which may coalesce with the saddle node in a Bogdanov-Takens point, and a
      symmetry-breaking spatially inhomogeneous pitchfork bifurcation. We verify the
      existence of these bifurcations in numerical simulations. The parameters of the
      normal form are determined and its predictions are tested against numerical
      simulations of partial differential equation models of excitable media with good
      agreement.

PMID- 16599754
TI  - Controlling chaos in spatially extended beam-plasma system by the continuous
      delayed feedback.
AB  - In this paper we discuss the control of complex spatio-temporal dynamics in a
      spatially extended nonlinear system (fluid model of Pierce diode) based on the
      concepts of controlling chaos in the systems with few degrees of freedom. A
      presented method is connected with stabilization of unstable homogeneous
      equilibrium state and the unstable spatio-temporal periodical states analogous to
      unstable periodic orbits of chaotic dynamics of the systems with few degrees of
      freedom. We show that this method is effective and allows to achieve desired
      regular dynamics chosen from a number of possible in the considered system.

PMID- 16599755
TI  - Synchronization in nonidentical complex Ginzburg-Landau equations.
AB  - A cross-correlation coefficient of complex fields has been investigated for
      diagnosing spatiotemporal synchronization behavior of coupled complex fields. We
      have also generalized the subsystem synchronization way established in low
      dimensional systems to one- and two-dimensional Ginzburg-Landau equations. By
      applying the indicator to examine the synchronization behavior of coupled
      Ginzburg-Landau equations, it is shown that our subsystem approach may be of
      better synchronization performance than the linear feedback method. For the
      linear feedback Ginzburg-Landau equation, the nonidentical system exhibits
      generalized synchronization characteristics in both amplitude and phase. However,
      the nonidentical subsystem may exhibit complete-like synchronization properties.
      The difference between complex fields for driven and response systems gives a
      linear scaling with the change of their parameter difference.

PMID- 16599756
TI  - Geometric diagnostics of complex patterns: spiral defect chaos.
AB  - Motivated by the observation of spiral patterns in a wide range of physical,
      chemical, and biological systems, we present an automated approach that aims at
      characterizing quantitatively spiral-like elements in complex stripe-like
      patterns. The approach provides the location of the spiral tip and the size of
      the spiral arms in terms of their arc length and their winding number. In
      addition, it yields the number of pattern components (Betti number of order 1),
      as well as their size and certain aspects of their shape. We apply the method to
      spiral defect chaos in thermally driven Rayleigh-Benard convection and find that
      the arc length of spirals decreases monotonically with decreasing Prandtl number
      of the fluid and increasing heating. By contrast, the winding number of the
      spirals is nonmonotonic in the heating. The distribution function for the number
      of spirals is significantly narrower than a Poisson distribution. The
      distribution function for the winding number shows approximately an exponential
      decay. It depends only weakly on the heating, but strongly on the Prandtl number.
      Large spirals arise only for larger Prandtl numbers (Pr approximately > 1). In
      this regime the joint distribution for the spiral length and the winding number
      exhibits a three-peak structure, indicating the dominance of Archimedean spirals
      of opposite sign and relatively straight sections. For small Prandtl numbers the
      distribution function reveals a large number of small compact pattern components.

PMID- 16599757
TI  - Chaotic synchronization: a nonlinear predictive filtering approach.
AB  - The synchronization of chaotic systems is a difficult task due to their sensitive
      dependence on the initial conditions. Perfect synchronization is almost
      impossible when noise is present in the system. One of the well known stochastic
      filtering algorithms that is used to synchronize chaotic systems in the presence
      of noise is the extended Kalman filter (EKF). However, for highly nonlinear
      systems, the approximation error introduced by the EKF has been shown to be
      relatively high. In this paper, a nonlinear predictive filter (NPF) is proposed
      for synchronizing chaotic systems. In this scheme, it is not required to
      approximate the underlying nonlinearity and hence there is no need to compute the
      Jacobian of the chaotic system. Numerical simulations are carried out to compare
      the performances of the NPF and EKF algorithms for synchronizing different sets
      of chaotic systems and/or maps. The well known Lorenz and Mackey-Glass systems as
      well as Ikeda map are used for numerical evaluation of the performance. Results
      clearly show that the NPF based approach is superior to the EKF based approach in
      terms of the normalized mean square error (NMSE), total NMSE, and the time taken
      for synchronization (measured in terms of the normalized instantaneous square
      error) for all the systems and/or maps considered.

PMID- 16599758
TI  - Synchronization of electronic genetic networks.
AB  - We describe a simple analog electronic circuit that mimics the behavior of a well
      known synthetic gene oscillator, the repressilator, which represents a set of
      three genes repressing one another. Synchronization of a population of such units
      is thoroughly studied, with the aim to compare the role of global coupling with
      that of global forcing on the population. Our results show that coupling is much
      more efficient than forcing in leading the gene population to synchronized
      oscillations. Furthermore, a modification of the proposed analog circuit leads to
      a simple electronic version of a genetic toggle switch, which is a simple network
      of two mutual repressor genes, where control by external forcing is also
      analyzed.

PMID- 16599759
TI  - Chaotic dynamics of a passively mode-locked soliton fiber ring laser.
AB  - We report on the experimental and numerical studies of the chaotic dynamics of a
      soliton fiber ring laser passively mode-locked by using the nonlinear
      polarization rotation (NPR) technique. Period-doubling route to chaos on the
      soliton repetition rate of either the single pulse soliton or the bound solitons
      of the laser was experimentally observed. Based on a coupled complex Ginzburg
      Landau equation model and also taking into account the laser cavity effect, we
      further show numerically that the period-doubling bifurcations and route to chaos
      are intrinsic properties of the laser, whose appearance is independent of the
      details of the laser cavity design and the laser soliton operation. Property of
      the solitons under the dynamical bifurcations is also numerically investigated.

PMID- 16599760
TI  - One-particle and few-particle billiards.
AB  - We study the dynamics of one-particle and few-particle billiard systems in
      containers of various shapes. In few-particle systems, the particles collide
      elastically both against the boundary and against each other. In the one-particle
      case, we investigate the formation and destruction of resonance islands in
      (generalized) mushroom billiards, which are a recently discovered class of
      Hamiltonian systems with mixed regular-chaotic dynamics. In the few-particle
      case, we compare the dynamics in container geometries whose counterpart one
      particle billiards are integrable, chaotic, and mixed. One of our findings is
      that two-, three-, and four-particle billiards confined to containers with
      integrable one-particle counterparts inherit some integrals of motion and exhibit
      a regular partition of phase space into ergodic components of positive measure.
      Therefore, the shape of a container matters not only for noninteracting particles
      but also for interacting particles.

PMID- 16599761
TI  - Measures of chaos and equipartition in integrable and nonintegrable lattices.
AB  - We have simulated numerically the behavior of the one-dimensional, periodic FPU
      alpha and Toda lattices to optical and acoustic initial excitations of small--but
      finite and large amplitudes. For the small-through-intermediate amplitudes (small
      initial energy per particle) we find nearly recurrent solutions, where the
      acoustic result is due to the appearance of solitons and where the optical result
      is due to the appearance of localized breather-like packets. For large
      amplitudes, we find complex-but-regular behavior for the Toda lattice and
      "stochastic" or chaotic behaviors for the alpha lattice. We have used the well
      known diagnostics: Localization parameter; Lyapounov exponent, and slope of a
      linear fit to linear normal mode energy spectra. Space-time diagrams of local
      particle energy and a wave-related quantity, a discretized Riemann invariant are
      also shown. The discretized Riemann invariants of the alpha lattice reveal
      soliton and near-soliton properties for acoustic excitations. Except for the
      localization parameter, there is a clear separation in behaviors at long-time
      between integrable and nonintegrable systems.

PMID- 16599762
TI  - Dispersion relation of the nonlinear Klein-Gordon equation through a variational
      method.
AB  - We derive approximate expressions for the dispersion relation of the nonlinear
      Klein-Gordon equation in the case of strong nonlinearities using a method based
      on the linear delta expansion. All the results obtained in this article are fully
      analytical, never involve the use of special functions, and can be used to obtain
      systematic approximations to the exact results to any desired degree of accuracy.
      We compare our findings with similar results in the literature and show that our
      approach leads to better and simpler results.

PMID- 16599763
TI  - Controlling chaotic robots with kinematical redundancy.
AB  - Robots with kinematical redundancy under the pseudoinverse control exhibit
      undesirable chaotic joint motion, which leads to erratic behaviors. In this
      study, we used the delayed feedback method to control chaotic motions of a planar
      3R rigid and a planar 3R flexible redundant robot under the pseudoinverse control
      when the end-effector traces a closed-path repeatedly in the work space. It was
      demonstrated that chaotic motions of robots with kinematical redundancy can be
      turned into regular motion when the delayed feedback method was applied with some
      appropriate parameters. This study provides a new insight helpful to solve the
      repeatability problem of redundant manipulators.

PMID- 16599764
TI  - Adaptive synchronization of neural networks with or without time-varying delay.
AB  - In this paper, based on the invariant principle of functional differential
      equations, a simple, analytical, and rigorous adaptive feedback scheme is
      proposed for the synchronization of almost all kinds of coupled identical neural
      networks with time-varying delay, which can be chaotic, periodic, etc. We do not
      assume that the concrete values of the connection weight matrix and the delayed
      connection weight matrix are known. We show that two coupled identical neural
      networks with or without time-varying delay can achieve synchronization by
      enhancing the coupling strength dynamically. The update gain of coupling strength
      can be properly chosen to adjust the speed of achieving synchronization. Also, it
      is quite robust against the effect of noise and simple to implement in practice.
      In addition, numerical simulations are given to show the effectiveness of the
      proposed synchronization method.

PMID- 16599765
TI  - Using white noise to enhance synchronization of coupled chaotic systems.
AB  - In the paper, complete synchronization of two chaotic oscillators via
      unidirectional coupling determined by white noise distribution is investigated.
      It is analytically proved that chaos synchronization could be achieved with
      probability one merely via white-noise-based coupling. The established
      theoretical result supports the observation of an interesting phenomenon that a
      certain kind of white noise could enhance chaos synchronization between two
      chaotic oscillators. Furthermore, numerical examples are provided to illustrate
      some possible applications of the theoretical result.

PMID- 16599766
TI  - Power-law scaling for macroscopic entropy and microscopic complexity: evidence
      from human movement and posture.
AB  - We investigated the relationship between macroscopic entropy and microscopic
      complexity of the dynamics of body rocking and sitting still across adults with
      stereotyped movement disorder and mental retardation (profound and severe)
      against controls matched for age, height, and weight. This analysis was performed
      through the examination of center of pressure (COP) motion on the mediolateral
      (side-to-side) and anteroposterior (fore-aft) dimensions and the entropy of the
      relative phase between the two dimensions of motion. Intentional body rocking and
      stereotypical body rocking possessed similar slopes for their respective
      frequency spectra, but differences were revealed during maintenance of sitting
      postures. The dynamics of sitting in the control group produced lower spectral
      slopes and higher complexity (approximate entropy). In the controls, the higher
      complexity found on each dimension of motion was related to a weaker coupling
      between dimensions. Information entropy of the relative phase between the two
      dimensions of COP motion and irregularity (complexity) of their respective
      motions fitted a power-law function, revealing a relationship between macroscopic
      entropy and microscopic complexity across both groups and behaviors. This power
      law relation affords the postulation that the organization of movement and
      posture dynamics occurs as a fractal process.

PMID- 16599767
TI  - Introduction: stability and pattern formation in networks of dynamical systems.

PMID- 16599768
TI  - Synchronization in asymmetrically coupled networks with node balance.
AB  - We study global stability of synchronization in asymmetrically connected networks
      of limit-cycle or chaotic oscillators. We extend the connection graph stability
      method to directed graphs with node balance, the property that all nodes in the
      network have equal input and output weight sums. We obtain the same upper bound
      for synchronization in asymmetrically connected networks as in the network with a
      symmetrized matrix, provided that the condition of node balance is satisfied. In
      terms of graphs, the symmetrization operation amounts to replacing each directed
      edge by an undirected edge of half the coupling strength. It should be stressed
      that without node balance this property in general does not hold.

PMID- 16599769
TI  - The size of the sync basin.
AB  - We suggest a new line of research that we hope will appeal to the nonlinear
      dynamics community, especially the readers of this Focus Issue. Consider a
      network of identical oscillators. Suppose the synchronous state is locally stable
      but not globally stable; it competes with other attractors for the available
      phase space. How likely is the system to synchronize, starting from a random
      initial condition? And how does the probability of synchronization depend on the
      way the network is connected? On the one hand, such questions are inherently
      difficult because they require calculation of a global geometric quantity, the
      size of the "sync basin" (or, more formally, the measure of the basin of
      attraction for the synchronous state). On the other hand, these questions are
      wide open, important in many real-world settings, and approachable by numerical
      experiments on various combinations of dynamical systems and network topologies.
      To give a case study in this direction, we report results on the sync basin for a
      ring of n >> 1 identical phase oscillators with sinusoidal coupling. Each
      oscillator interacts equally with its k nearest neighbors on either side. For k/n
      greater than a critical value (approximately 0.34, obtained analytically), we
      show that the sync basin is the whole phase space, except for a set of measure
      zero. As k/n passes below this critical value, coexisting attractors are born in
      a well-defined sequence. These take the form of uniformly twisted waves, each
      characterized by an integer winding number q, the number of complete phase twists
      in one circuit around the ring. The maximum stable twist is proportional to n/k;
      the constant of proportionality is also obtained analytically. For large values
      of n/k, corresponding to large rings or short-range coupling, many different
      twisted states compete for their share of phase space. Our simulations reveal
      that their basin sizes obey a tantalizingly simple statistical law: the
      probability that the final state has q twists follows a Gaussian distribution
      with respect to q. Furthermore, as n/k increases, the standard deviation of this
      distribution grows linearly with square root of n/k. We have been unable to
      explain either of these last two results by anything beyond a hand-waving
      argument.

PMID- 16599770
TI  - Hierarchical synchronization in complex networks with heterogeneous degrees.
AB  - We study synchronization behavior in networks of coupled chaotic oscillators with
      heterogeneous connection degrees. Our focus is on regimes away from the complete
      synchronization state, when the coupling is not strong enough, when the
      oscillators are under the influence of noise or when the oscillators are
      nonidentical. We have found a hierarchical organization of the synchronization
      behavior with respect to the collective dynamics of the network. Oscillators with
      more connections (hubs) are synchronized more closely by the collective dynamics
      and constitute the dynamical core of the network. The numerical observation of
      this hierarchical synchronization is supported with an analysis based on a mean
      field approximation and the master stability function.

PMID- 16599772
TI  - Synchronizing weighted complex networks.
AB  - Real networks often consist of local units, which interact with each other via
      asymmetric and heterogeneous connections. In this work, we explore the
      constructive role played by such a directed and weighted wiring for the
      synchronization of networks of coupled dynamical systems. The stability condition
      for the synchronous state is obtained from the spectrum of the respective
      coupling matrices. In particular, we consider a coupling scheme in which the
      relative importance of a link depends on the number of shortest paths through it.
      We illustrate our findings for networks with different topologies: scale free,
      small world, and random wirings.

PMID- 16599771
TI  - Synchronization in complex networks with a modular structure.
AB  - Networks with a community (or modular) structure arise in social and biological
      sciences. In such a network individuals tend to form local communities, each
      having dense internal connections. The linkage among the communities is, however,
      much more sparse. The dynamics on modular networks, for instance synchronization,
      may be of great social or biological interest. (Here by synchronization we mean
      some synchronous behavior among the nodes in the network, not, for example,
      partially synchronous behavior in the network or the synchronizability of the
      network with some external dynamics.) By using a recent theoretical framework,
      the master-stability approach originally introduced by Pecora and Carroll in the
      context of synchronization in coupled nonlinear oscillators, we address
      synchronization in complex modular networks. We use a prototype model and develop
      scaling relations for the network synchronizability with respect to variations of
      some key network structural parameters. Our results indicate that random, long
      range links among distant modules is the key to synchronization. As an
      application we suggest a viable strategy to achieve synchronous behavior in
      social networks.

PMID- 16599773
TI  - Synchronization in large directed networks of coupled phase oscillators.
AB  - We study the emergence of collective synchronization in large directed networks
      of heterogeneous oscillators by generalizing the classical Kuramoto model of
      globally coupled phase oscillators to more realistic networks. We extend recent
      theoretical approximations describing the transition to synchronization in large
      undirected networks of coupled phase oscillators to the case of directed
      networks. We also consider the case of networks with mixed positive-negative
      coupling strengths. We compare our theory with numerical simulations and find
      good agreement.

PMID- 16599774
TI  - Speed of synchronization in complex networks of neural oscillators: analytic
      results based on Random Matrix Theory.
AB  - We analyze the dynamics of networks of spiking neural oscillators. First, we
      present an exact linear stability theory of the synchronous state for networks of
      arbitrary connectivity. For general neuron rise functions, stability is
      determined by multiple operators, for which standard analysis is not suitable. We
      describe a general nonstandard solution to the multioperator problem.
      Subsequently, we derive a class of neuronal rise functions for which all
      stability operators become degenerate and standard eigenvalue analysis becomes a
      suitable tool. Interestingly, this class is found to consist of networks of leaky
      integrate-and-fire neurons. For random networks of inhibitory integrate-and-fire
      neurons, we then develop an analytical approach, based on the theory of random
      matrices, to precisely determine the eigenvalue distributions of the stability
      operators. This yields the asymptotic relaxation time for perturbations to the
      synchronous state which provides the characteristic time scale on which neurons
      can coordinate their activity in such networks. For networks with finite in
      degree, i.e., finite number of presynaptic inputs per neuron, we find a speed
      limit to coordinating spiking activity. Even with arbitrarily strong interaction
      strengths neurons cannot synchronize faster than at a certain maximal speed
      determined by the typical in-degree.

PMID- 16599775
TI  - Synchronization in networks with random interactions: theory and applications.
AB  - Synchronization is an emergent property in networks of interacting dynamical
      elements. Here we review some recent results on synchronization in randomly
      coupled networks. Asymptotical behavior of random matrices is summarized and its
      impact on the synchronization of network dynamics is presented. Robert May's
      results on the stability of equilibrium points in linear dynamics are first
      extended to systems with time delayed coupling and then nonlinear systems where
      the synchronized dynamics can be periodic or chaotic. Finally, applications of
      our results to neuroscience, in particular, networks of Hodgkin-Huxley neurons,
      are included.

PMID- 16599776
TI  - Spatiotemporal dynamics of networks of excitable nodes.
AB  - A network of excitable nodes based on the photosensitive Belousov-Zhabotinsky
      reaction is studied in experiments and simulations. The addressable medium allows
      both local and nonlocal links between the nodes. The initial spread of excitation
      across the network as well as the asymptotic oscillatory behavior are described.
      Synchronization of the spatiotemporal dynamics occurs by entrainment to high
      frequency network pacemakers formed by excitation loops. Analysis of the
      asymptotic behavior reveals that the dynamics of the network is governed by a
      subnetwork selected during the initial transient period.

PMID- 16599777
TI  - Synchronization and time shifts of dynamical patterns for mutually delay-coupled
      fiber ring lasers.
AB  - A pair of coupled erbium doped fiber ring lasers is used to explore the dynamics
      of coupled spatiotemporal systems. The lasers are mutually coupled with a
      coupling delay less than the cavity round-trip time. We study synchronization
      between the two lasers in the experiment and in a delay differential equation
      model of the system. Because the lasers are internally perturbed by spontaneous
      emission, we include a noise source in the model to obtain stochastic
      realizations of the deterministic equations. Both amplitude synchronization and
      phase synchronization are considered. We use the Hilbert transform to define the
      phase variable and compute phase synchronization. We find that synchronization
      increases with coupling strength in the experiment and the model. When the time
      series from two lasers are time shifted in either direction by the delay time,
      approximately equal synchronization is frequently observed, so that a clear
      leader and follower cannot be identified. We define an algorithm to determine
      which laser leads the other when the synchronization is sufficiently different
      with one direction of time shift, and statistics of switches in leader and
      follower are studied. The frequency of switching between leader and follower
      increases with coupling strength, as might be expected since the lasers mutually
      influence each other more effectively with stronger coupling.

PMID- 16599778
TI  - Functional holography analysis: simplifying the complexity of dynamical networks.
AB  - We present a novel functional holography (FH) analysis devised to study the
      dynamics of task-performing dynamical networks. The latter term refers to
      networks composed of dynamical systems or elements, like gene networks or neural
      networks. The new approach is based on the realization that task-performing
      networks follow some underlying principles that are reflected in their activity.
      Therefore, the analysis is designed to decipher the existence of simple causal
      motives that are expected to be embedded in the observed complex activity of the
      networks under study. First we evaluate the matrix of similarities (correlations)
      between the activities of the network's components. We then perform collective
      normalization of the similarities (or affinity transformation) to construct a
      matrix of functional correlations. Using dimension reduction algorithms on the
      affinity matrix, the matrix is projected onto a principal three-dimensional space
      of the leading eigenvectors computed by the algorithm. To retrieve back
      information that is lost in the dimension reduction, we connect the nodes by
      colored lines that represent the level of the similarities to construct a
      holographic network in the principal space. Next we calculate the activity
      propagation in the network (temporal ordering) using different methods like
      temporal center of mass and cross correlations. The causal information is
      superimposed on the holographic network by coloring the nodes locations according
      to the temporal ordering of their activities. First, we illustrate the analysis
      for simple, artificially constructed examples. Then we demonstrate that by
      applying the FH analysis to modeled and real neural networks as well as recorded
      brain activity, hidden causal manifolds with simple yet characteristic
      geometrical and topological features are deciphered in the complex activity. The
      term "functional holography" is used to indicate that the goal of the analysis is
      to extract the maximum amount of functional information about the dynamical
      network as a whole unit.

PMID- 16599779
TI  - Centrality in networks of urban streets.
AB  - Centrality has revealed crucial for understanding the structural properties of
      complex relational networks. Centrality is also relevant for various spatial
      factors affecting human life and behaviors in cities. Here, we present a
      comprehensive study of centrality distributions over geographic networks of urban
      streets. Five different measures of centrality, namely degree, closeness,
      betweenness, straightness and information, are compared over 18 1-square-mile
      samples of different world cities. Samples are represented by primal geographic
      graphs, i.e., valued graphs defined by metric rather than topologic distance
      where intersections are turned into nodes and streets into edges. The spatial
      behavior of centrality indices over the networks is investigated graphically by
      means of color-coded maps. The results indicate that a spatial analysis, that we
      term multiple centrality assessment, grounded not on a single but on a set of
      different centrality indices, allows an extended comprehension of the city
      structure, nicely capturing the skeleton of most central routes and subareas that
      so much impacts on spatial cognition and on collective dynamical behaviors.
      Statistically, closeness, straightness and betweenness turn out to follow similar
      functional distribution in all cases, despite the extreme diversity of the
      considered cities. Conversely, information is found to be exponential in planned
      cities and to follow a power-law scaling in self-organized cities. Hierarchical
      clustering analysis, based either on the Gini coefficients of the centrality
      distributions, or on the correlation between different centrality measures, is
      able to characterize classes of cities.

PMID- 16599781
TI  - Rotation sets for networks of circle maps.
AB  - We consider continuous maps of the torus, homotopic to the identity, that arise
      from systems of coupled circle maps and discuss the relationship between network
      architecture and rotation sets. Our main result is that when the map on the torus
      is invertible, network architecture can force the set of rotation vectors to lie
      in a low-dimensional subspace. In particular, the rotation set for an all-to-all
      coupled system of identical cells must be a subset of a line.

PMID- 16599780
TI  - Scale-free topologies and activatory-inhibitory interactions.
AB  - A simple model of activatory-inhibitory interactions controlling the activity of
      agents (substrates) through a "saturated response" dynamical rule in a scale-free
      network is thoroughly studied. After discussing the most remarkable dynamical
      features of the model, namely fragmentation and multistability, we present a
      characterization of the temporal (periodic and chaotic) fluctuations of the quasi
      stasis asymptotic states of network activity. The double (both structural and
      dynamical) source of entangled complexity of the system temporal fluctuations, as
      an important partial aspect of the correlation structure-function problem, is
      further discussed in light of the numerical results, with a view on potential
      applications of these general results.

PMID- 16599782
TI  - Dynamical network interactions in distributed control of robots.
AB  - In this paper the dynamical network model of the interactions within a group of
      mobile robots is investigated and proposed as a possible strategy for controlling
      the robots without central coordination. Motivated by the results of the analysis
      of our simple model, we show that the system performance in the presence of noise
      can be improved by including long-range connections between the robots. Finally,
      a suitable strategy based on this model to control exploration and transport is
      introduced.

PMID- 16599783
TI  - Synchronized state of coupled dynamics on time-varying networks.
AB  - We consider synchronization properties of coupled dynamics on time-varying
      networks and the corresponding time-average network. We find that if the
      different Laplacians corresponding to the time-varying networks commute with each
      other then the stability of the synchronized state for both the time-varying and
      the time-average topologies are approximately the same. On the other hand for
      noncommuting Laplacians the stability of the synchronized state for the time
      varying topology is in general better than the time-average topology.

PMID- 16599786
TI  - Who wants to be a psychologist?
AB  - Every significant piece of public policy, every important generalization in
      history, economics, political science, and sociology depends on (largely
      unevaluated) assumptions about human nature. Personality psychology concerns the
      nature of human nature; it is, therefore, concerned with one of the most powerful
      and dangerous forces on earth. Developing adequate methods for conceptualizing
      human nature and forecasting significant components of social behavior-for
      example, integrity, creativity, leadership-would seem to be a matter of real
      urgency. Nonetheless, personality psychology has a minor and marginal status in
      academic psychology. I have spent my career trying to understand the origins of
      human behavior, trying to develop measurement models for capturing key elements
      of social performance, and trying to defend the study of personality against the
      complaints of a seemingly endless supply of academic critics.

PMID- 16599787
TI  - Sequelae of child sexual abuse: a child and parent assessment.
AB  - We present a case example of a 9-year-old, biracial girl and her mother. We
      integrate data collected from rating scales (e.g., Child Behavior Checklist;
      Achenbach & Rescorla, 2001), a free response measure (Thematic Apperception Test;
      Murray, 1943), and a direct observation measure (Parent-Child Interaction
      Assessment-II; Holigrocki, Kaminski, & Frieswyk, 1999, 2002) and reveal how a
      child sexual abuse victim's internal representations and symptoms manifest in
      both an interpersonal context and in the realm of play. We discuss assessment
      findings regarding how they provide for an idiographic understanding of the
      child.

PMID- 16599788
TI  - A comparison of mean partialing and dual-hypothesis testing to evaluate
      stereotype effects when assessing profile similarity.
AB  - Assessing profile similarity is an important task in research and clinical
      practice, but conclusions about profile similarity may be confounded by
      stereotype effects that create artificially similar profiles. In this article, we
      review the impact of stereotype effects on profile similarity and a conventional
      approach to addressing this confound (i.e., mean partialing). We argue that a
      dual-hypothesis testing approach distinguishing the no-effect null hypothesis
      (i.e., is the observed similarity different from zero?) from the chance-effect
      null hypothesis (i.e., is the observed similarity different from chance given the
      distribution of profile elements?) can provide a more nuanced understanding of
      profile similarity. To compare results from these 2 perspectives, we analyzed
      data from 2 samples using within-persons correlations as indexes of similar
      profile shapes. Results indicated that a dual-hypothesis testing approach led to
      more conservative conclusions about profile similarity (i.e., fewer Type 1
      errors) than mean partialing and may be especially valuable when dealing with
      moderate-sized stereotype effects. Both approaches led to identical conclusions
      when stereotype effects were largest. Conclusions emphasize the relative merits
      and limitations of the dual-hypothesis testing approach as well as potential
      future applications in the personality assessment domain.

PMID- 16599789
TI  - The scale of ethnic experience: development and psychometric properties.
AB  - The Scale of Ethnic Experience (SEE) is a new self-report instrument designed to
      measure multiple ethnicity-related cognitive constructs across ethnic groups. We
      present the development and psychometric properties here. We generated and
      refined an item pool using expert consultants and culturally diverse focus
      groups. We derived a final 32-item version of the SEE based on separate factor
      analyses of data from college students in 4 ethnic groups: African Americans,
      Caucasian Americans, Filipino Americans, and Mexican Americans. Four factors were
      consistent across the ethnic groups: Ethnic Identity, Perceived Discrimination,
      Mainstream Comfort, and Social Affiliation. We found evidence of test-retest
      reliability, internal consistency, and criterion and construct validity for all
      groups. Finally, we cross-validated the factor structure of the SEE in a
      culturally diverse sample. Results support the reliability and validity of the
      SEE as a multidimensional measure of ethnicity-related cognitive constructs that
      can be used across American ethnic groups.

PMID- 16599790
TI  - Construct validity of the relationship profile test: three-year retest
      reliability and links with core personality traits, object relations, and
      interpersonal problems.
AB  - The Relationship Profile Test (RPT; Bornstein & Languirand, 2003) is a 30-item
      self-report measure of destructive overdependence, dysfunctional detachment, and
      healthy dependency. Previous research has shown that the 3 RPT subscales have
      adequate internal consistency, good retest reliability over 23 and 85 weeks, and
      good convergent and discriminant validity with respect to measures of attachment
      style, relatedness, gender role, self-concept, alexithymia, locus of control,
      need for approval, and life satisfaction. In this investigation, we assessed the
      3-year retest reliability of RPT scores in a northeastern liberal arts college
      student sample (Study 1) and evaluated the convergent and discriminant validity
      of RPT scores in a southern university sample (Study 2). Results generally
      supported the long-term stability and convergent and discriminant validity of RPT
      scores but also pointed to some limitations of the measure. We discuss
      implications of these results and describe future research directions.

PMID- 16599791
TI  - A confirmatory test of the underlying factor structure of scores on the
      collective self-esteem scale in two independent samples of Black Americans.
AB  - In this study, we examined the factor structure of the Collective Self-Esteem
      Scale (CSES; Luhtanen & Crocker, 1992) across 2 separate samples of Black
      Americans. The CSES was administered to a sample of Black American adolescents (n
      = 538) and a community sample of Black American adults (n = 313). Results of
      confirmatory factor analyses (CFAs), however, did not support the original 4
      factor model identified by Luhtanen and Crocker (1992) as providing an adequate
      fit to the data for these samples. Furthermore, an exploratory CFA procedure
      failed to find a CSES factor structure that could be replicated across the 2
      samples of Black Americans. We present and discuss implications of the findings.

PMID- 16599792
TI  - A psychometric evaluation of the Rorschach comprehensive system's perceptual
      thinking index.
AB  - In this study, we investigated evidence for reliability and validity of the
      Perceptual Thinking Index (PTI; Exner, 2000a, 2000b) among an adult inpatient
      population. We conducted reliability and validity analyses on 107 patients who
      met the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text
      revision; American Psychiatric Association, 2000) criteria for a schizophrenia
      spectrum disorder (SSD) or mood disorder with no psychotic features (MD). Results
      provided support for interrater reliability as well as internal consistency of
      the PTI. Furthermore, the PTI was an effective index in differentiating SSD
      patients from patients diagnosed with an MD. Finally, the PTI demonstrated
      adequate diagnostic statistics that can be useful in the classification of
      patients diagnosed with SSD and MD. We discuss methodological issues,
      implications for assessment practice, and directions for future research.

PMID- 16599793
TI  - Updating the Jesness Inventory randomness validity scales for the Jesness
      Inventory-Revised.
AB  - I updated 2 previously developed randomness scales for the Jesness Inventory
      (Jesness, 1983)-the Jesness Variable Response Inconsistency scale (J-VRIN) and
      the Variable Response scale (J-VR)-for the Jesness Inventory-Revised (Jesness-R;
      Jesness, 2003). I investigated efficacies for those 2 scales and a 3rd randomness
      scale described in the Jesness-R manual, the Randomness scale (J-RR), by
      comparing 76 protocols of delinquents, ages 13 to 17 years, screened for probable
      randomness with a matched-pair MMPI-Adolescent (Butcher et al., 1992) or a Millon
      Adolescent Clinical Inventory (Millon, Millon, & Davis, 1993), with 100 all
      random protocols, and 40 partially random protocols. J-VRIN and J-VR in
      conjunction successfully detected 98% of the all-random protocols and 83% of the
      partially random protocols. J-RR successfully detected 19% and 10%, respectively.
      I report predictive power and overall effectiveness for base rates of .10 and
      .20.

PMID- 16599794
TI  - Incremental validity of the MMPI-2 Restructured Clinical (RC) scales in a private
      practice sample.
AB  - Building on results reported in Sellbom, Graham, and Schenk (2005), in this
      study, we examined the incremental validity of the newly introduced MMPI-2
      (Butcher et al., 2001) Restructured Clinical (RC) scales (Tellegen et al., 2003)
      over both the Clinical and Content scales. Participants were 647 clients in
      private practice who were administered the MMPI-2 and the Multiaxial Diagnostic
      Inventory (Doverspike, 1990) early in therapy. The results indicate that the RC
      scales had acceptable internal consistency, reduced intercorrelations (compared
      to the Clinical scales), and promising convergent and discriminant validity.
      Hierarchical regression analyses revealed that the RC scales added incrementally
      to both the Clinical and Content scales in predicting self reported clinical
      symptoms. These findings suggest that the RC scales are relatively homogenous
      measures of core clinical constructs that can add unique information to the
      understanding of private practice clients above and beyond the Clinical and
      Content scales.

PMID- 16599795
TI  - Measurement of agency, communion, and emotional vulnerability with the Personal
      Attributes Questionnaire.
AB  - Factor analytic studies of the 24-item Personal Attributes Questionnaire (Spence
      & Helmreich, 1978) have reported inconsistent results, and a previous
      confirmatory factor analysis (CFA) indicated inadequate fit for factors
      corresponding to Masculinity, Femininity, and Masculinity-Femininity scales. In
      this research, we used CFA in a college sample (N = 382) to evaluate the 3-factor
      model, and we revised scales by eliminating 6 misspecified items. The revised
      model fit well in another college sample (N = 230). We renamed the revised scales
      Agency, Communion, and Emotional Vulnerability. In relation to Five-factor
      theory, Emotional Vulnerability and Communion correlated well with Neuroticism
      and Agreeableness, respectively, and Agency had moderate correlations with
      Neuroticism, Extraversion, and Conscientiousness. Psychometric results in the
      context of current theory suggest that Agency (Masculinity) may not be a fully
      adequate measure of the agency construct.

PMID- 16599796
TI  - MMPI-2 assessment of malingered emotional distress related to a workplace injury:
      a mixed group validation.
AB  - In this study, we examined the capacity of MMPI-2 (Butcher, Dahlstrom, Graham,
      Tellegen, & Kaemmer, 2001) validity indexes to identify malingered depression
      associated with a workplace injury. We compared 27 graduate students simulating
      depression with archival records of 33 inpatients diagnosed with major depressive
      disorder. We employed a mixed-group validation design to generate true positive
      rates (TPR) and false positive rates (FPR) for the various MMPI-2 validity scales
      [F, FB, F(p), FBS, F - K, Ds2] while we accounted for base rates of malingering
      in each sample. The Fake Bad scale (FBS) was the only validity measure that
      produced acceptable TPR and FPR or a significant correlation with malingering
      status.

PMID- 16599797
TI  - Reanalysis of the Gronnerod (2003) Rorschach temporal stability meta-analysis
      data set.
AB  - I reanalyzed the Gronnerod (2003) Rorschach temporal stability meta-analysis data
      with a theoretically driven hierarchical regression analysis. I also examined the
      intrarater reliability of initial coding decisions and verified their
      consistency. In the new regression analyses, retest period strengthened its
      influence on stability, whereas methodological factors showed a tendency toward
      influence. The new results are more in line with the results from Gronnerod's
      (2004) psychotherapy change meta-analysis results.

PMID- 16599798
TI  - Wanted: research on applied clinical judgment in personality assessment.

PMID- 16599799
TI  - Illusions about illusory mental health: comments on Joiner et al. (2005).

PMID- 16599803
TI  - Reflections on physical chemistry: Science and scientists.
AB  - This is the story of a young person who grew up in Tel-Aviv during the period of
      the establishment of the State of Israel and was inspired to become a physical
      chemist by the cultural environment, by the excellent high-school education, and
      by having been trained by some outstanding scientists at the Hebrew University of
      Jerusalem and, subsequently, by the intellectual environment and high-quality
      scientific endeavor at the University of Chicago. Since serving as the first
      chairman of the Chemistry Department of the newly formed Tel-Aviv University he
      has been immersed in research, in the training of young scientists, and in
      intensive and extensive international scientific collaboration. Together with the
      members of his "scientific family" he has explored the phenomena of energy
      acquisition, storage and disposal and structure-dynamics-function relations in
      large molecules, condensed phase, clusters and biomolecules, and is looking
      forward to many future adventures in physical chemistry.

PMID- 16599804
TI  - On a research rollercoaster with friends.

PMID- 16599805
TI  - 4D ultrafast electron diffraction, crystallography, and microscopy.
AB  - In this review, we highlight the progress made in the development of 4D ultrafast
      electron diffraction (UED), crystallography (UEC), and microscopy (UEM) with a
      focus on concepts, methodologies, and prototypical applications. The joint atomic
      scale resolutions in space and time, and sensitivity reached, make it possible to
      determine complex transient structures and assemblies in different phases. These
      applications include studies of isolated chemical reactions (molecular beams),
      interfaces, surfaces and nanocrystals, self-assembly, and 2D crystalline fatty
      acid bilayers. In 4D UEM, we are now able, using timed, single-electron packets,
      to image nano-to-micro scale structures of materials and biological cells. Future
      applications of these methods are foreseen across areas of physics, chemistry,
      and biology.

PMID- 16599806
TI  - Heterogeneous chemistry of carbon aerosols.
AB  - Atmospheric carbon particles originate from natural sources and from human
      activity. The processes that lead to their formation are varied and include
      fossil fuel combustion, biomass burning, and mechanical stress and wear of
      carbonaceous materials. In this review, we examine recent work on the structure
      and composition of carbon aerosol particles, and we describe how they react with
      the atmospherically abundant gases ozone, oxygen, sulfur dioxide, nitric acid,
      and nitrogen oxides. The study of carbon particles in the laboratory has shown
      that chemical reactivity depends strongly on the type of carbon used and on
      experimental conditions such as temperature and humidity. The variability in the
      results demonstrates the difficulty in extrapolating laboratory results to
      atmospheric conditions and in explaining the role of carbon particles in
      processes such as global warming and environmental chemical cycling.

PMID- 16599807
TI  - Progress in the theory of mixed quantum-classical dynamics.
AB  - Quantum-classical Liouville dynamics can be used to study the properties of open
      quantum systems that are coupled to bath or environmental degrees of freedom
      whose dynamics can be approximated by classical equations of motion. In contrast
      to many open quantum system approaches, quantum-classical dynamics provides a
      detailed description of the bath molecules. Such a description is especially
      appropriate for the study of quantum rate processes, such as proton and electron
      transport, where the detailed dynamics of the bath has a strong influence on the
      quantum rate. The quantum-classical Liouville equation can also serve as a
      starting point for the derivation of reduced descriptions where all or some of
      the bath degrees of freedom are projected out. Quantum-classical Liouville
      dynamics can be simulated in terms of an ensemble of surface-hopping trajectories
      whose character differs from that in other surface-hopping schemes. The results
      of studies of proton transfer in condensed phase and reactive dynamics in a
      dissipative environment are presented to illustrate applications of the
      formalism.

PMID- 16599808
TI  - Stark deceleration and trapping of OH radicals.
AB  - The motion of polar molecules can be controlled by time-varying inhomogeneous
      electric fields. In a Stark decelerator, this is exploited to accelerate,
      transport, or decelerate a fraction of a molecular beam. When combined with a
      trap, the decelerator provides a means to store the molecules for times up to
      seconds. Here, we review our efforts to produce cold molecules via this
      technique. In particular, we present a new generation Stark decelerator and
      electrostatic trap that selects a significant part of a molecular beam pulse that
      can be loaded into the trap. Deceleration and trapping experiments using a beam
      of OH radicals are discussed.

PMID- 16599809
TI  - Atmospheric field measurements of the hydroxyl radical using laser-induced
      fluorescence spectroscopy.
AB  - The hydroxyl radical, OH, is the most important cleansing agent in the Earth's
      atmosphere, removing the majority of trace gases by oxidation, including
      greenhouse gases and CFC replacements. It is intimately involved in the chemistry
      that generates photochemical smog, which includes many substances harmful to
      health, such as ozone and particulate matter. In this review, the technique of
      laser-induced fluorescence for the detection of OH in the atmosphere is
      described, using as an example the fluorescence assay by gas expansion (FAGE)
      instrument developed at the University of Leeds. The comparison of measured OH
      concentrations at a given field site with those calculated by an atmospheric
      model, which is a mathematical representation of the underlying chemistry,
      provides one of the best methods to test whether the key chemical and physical
      processes are understood. Examples are given for field measurements made in clean
      and polluted environments.

PMID- 16599810
TI  - Excitons in conjugated oligomer aggregates, films, and crystals.
AB  - Recent experimental and theoretical investigations of excitons in conjugated
      oligomer nanoaggregates, thin films, and crystals are reviewed. The review
      focuses on the technologically important unsubstituted oligo-phenylene vinylenes
      (OPVn) and oligo-thiophenes (OTn), which exhibit side-by-side herringbone crystal
      packing. Many of the salient photophysical properties displayed by OPVn and OTn
      solid phases, including the large Davydov splitting, the rich variety of peaks
      due to vibronic coupling in both absorption and emission, and the unusual
      behavior of the emission origin, are accounted for in a model including excitonic
      coupling between molecules, linear exciton-phonon coupling, and disorder.

PMID- 16599811
TI  - Laser probing of single-aerosol droplet dynamics.
AB  - Aerosols play a critical role in a diverse range of scientific disciplines. To
      characterize and quantify their role, it is essential that the fundamental
      details of mass and heat transfer between the aerosol particle and surrounding
      medium, the properties of multiphase droplets, and the coagulation of aerosol
      droplets be more fully explored. Elastic and inelastic light scattering can
      provide information on particle size, composition, morphology, and temperature.
      In addition, spatial inhomogeneities in composition and temperature can be
      probed. We review how such techniques can be used to develop an understanding of
      the chemical and physical dynamics of a single aerosol droplet.

PMID- 16599812
TI  - Connecting chemical dynamics in gases and liquids.
AB  - Modern ultrafast spectroscopic techniques provide new opportunities to study
      chemical reaction dynamics in liquids and hold the possibility of obtaining much
      of the same detailed information available in gases. Vibrational energy transfer
      studies are the most advanced of the investigations and demonstrate that it is
      possible to observe state-specific pathways of energy flow within a vibrationally
      excited molecule (intramolecular vibrational relaxation) and into the surrounding
      solvent molecules (intermolecular energy transfer). Energy transfer in liquids
      and gases share many common aspects, but the presence of the solvent also alters
      the relaxation in both obvious and subtle ways. Photodissociation is amenable to
      similarly detailed study in liquids, and there are informative new measurements.
      Bimolecular reactions have received the least attention in state-resolved
      measurements in liquids, but the means to carry them much further now exist.
      Studying photodissociation and bimolecular reaction of molecules prepared with
      initial vibrational excitation in liquids is a realistic, but challenging, goal.

PMID- 16599813
TI  - Near-field optical microscopy and spectroscopy with pointed probes.
AB  - In recent years, developments in near-field techniques exploiting far-field
      illumination of a pointed, apertureless probe have demonstrated a newfound
      excitement. This is due in part to the advantages afforded by apertureless
      techniques that allow for the practical implementation of spectroscopic contrast
      mechanisms at length scales below 100 nm. These mechanisms include Raman and
      infrared absorption for chemical contrast, as well as materials contrast based on
      dielectric dispersion. In this review, we briefly describe the evolution of the
      field from the "classical" aperture-based approach toward the development of near
      field optical microscopy with pointed probes. We highlight advances in state-of
      the-art theory that describe the field distribution under an illuminated probe,
      as well as advances in the experimental implementation of scattering and
      excitation probe techniques.

PMID- 16599814
TI  - On the nature of ions at the liquid water surface.
AB  - A qualitatively new understanding of the nature of ions at the liquid water
      surface is emerging. Traditionally, the characterization of liquid surfaces has
      been limited to macroscopic experimental techniques such as surface tension and
      electrostatic potential measurements, wherein the microscopic picture then has to
      be inferred by applying theoretical models. Because the surface tension of
      electrolyte solutions generally increases with ion concentration, all inorganic
      ions have been thought to be repelled from the air-water interface, leaving the
      outermost surface layer essentially devoid of ions. This oversimplified picture
      has recently been challenged: first by chemical kinetics measurements, then by
      theoretical molecular dynamics simulations using polarizable models, and most
      recently by new surface sensitive experimental observations. Here we present an
      overview of the nature of the interfacial structure of electrolyte solutions and
      give a detailed description of the new picture that is emerging.

PMID- 16599815
TI  - Correlated electronic structure nonlinear response methods for structured
      environments.
AB  - This contribution concerns a brief outline of structural environment models where
      correlated electronic structure response methods are utilized for the
      determination of nonlinear optical properties of molecules. The presentation
      provides theory and applications of a heterogeneous dielectric media model and a
      quantum mechanical-classical mechanical model at the level of correlated
      electronic structure response methods. The correlated electronic structure
      response methods include the multiconfigurational self-consistent field method.

PMID- 16599817
TI  - ION pair dissociation: Spectroscopy and dynamics.
AB  - Ion pair dissociation processes may be studied using coherent vacuum ultraviolet
      laser sources in a manner entirely analogous to photoelectron spectroscopy,
      albeit with the anion playing the role of a heavy electron. If the excitation
      energy is above the dissociation energy and the kinetic energy of the fragment is
      measured using ion imaging, this approach is termed ion pair imaging spectroscopy
      (IPIS) and is related to conventional photoelectron spectroscopy. If the
      excitation energy is just below the dissociation energy and pulsed-field
      dissociation is employed, this approach is analogous to mass analyzed threshold
      ionization (MATI) spectroscopy and is termed threshold ion pair production
      spectroscopy (TIPPS). These approaches provide a novel means of investigating ion
      thermochemistry and spectroscopy and superexcited state decay dynamics at high
      resolution.

PMID- 16599816
TI  - Coherent excitation of vibrational modes in metallic nanoparticles.
AB  - Excitation of metal nanoparticles with subpicosecond laser pulses causes a rapid
      increase in the lattice temperature, which can impulsively excite the phonon
      modes of the particle that correlate with the expansion coordinates. The
      vibrational periods depend on the size, shape, and elastic constants of the
      particles. Thus, time-resolved spectroscopy can be used to examine the material
      properties of nanometer-sized objects. This review provides a brief overview of
      the steady-state and time-resolved electronic spectroscopy of metal particles,
      which is important for understanding why vibrational motion appears in transient
      absorption traces. I also describe how the vibrational modes observed in the
      experiments are assigned, and what information can be obtained from the
      measurements. Our work has been mainly concerned with noble metal particles (gold
      and silver) in aqueous solution. The different shapes that have been examined to
      date include spheres, rods, and triangles, all with different sizes.

PMID- 16599818
TI  - Reactivity of the germanium surface: Chemical passivation and functionalization.
AB  - With the rapidly changing materials needs of modern microelectronics, germanium
      provides an opportunity for future-generation devices. Controlling germanium
      interfaces will be essential for this purpose. We review germanium surface
      reactivity, beginning with a description of the most commonly used surfaces,
      Ge(100) and Ge(111). An analysis of oxide formation shows why the poor oxide
      properties have hindered practical use of germanium to date. This is followed by
      an examination of alternate means of surface passivation, with particular
      attention given to sulfide, chloride, and hydride termination. Specific tailoring
      of the interface properties is possible through organic functionalization. The
      few solution functionalization methods that have been studied are reviewed.
      Vacuum functionalization has been studied to a much greater extent, with dative
      bonding and cycloaddition reactions emerging as principle reaction mechanisms.
      These are reviewed through molecular reaction studies that demonstrate the
      versatility of the germanium surface.

PMID- 16599819
TI  - Scanning tunneling microscopy manipulation of complex organic molecules on solid
      surfaces.
AB  - Organic molecules adsorbed on solid surfaces display a fascinating variety of new
      physical and chemical phenomena ranging from self-assembly and molecular
      recognition to nonlinear optical properties and current rectification. Both the
      fundamental interest in these systems and the promise of technological
      applications have motivated a strong research effort in understanding and
      controlling these properties. Scanning tunneling microscopy (STM) and, in
      particular, its ability to manipulate individual adsorbed molecules, has become a
      powerful tool for studying the adsorption geometry and the conformation and
      dynamics of single molecules and molecular aggregates. Here we review selected
      case studies demonstrating the enormous capabilities of STM manipulations to
      explore basic physiochemical properties of adsorbed molecules. In particular, we
      emphasize the role of STM manipulations in studying the coupling between the
      multiple degrees of freedom of adsorbed molecules, the phenomenon of molecular
      molding, and the possibility of creating and breaking individual chemical bonds
      in a controlled manner, i.e., the concept of single-molecule chemistry.

PMID- 16599821
TI  - Femtosecond time-resolved photoelectron imaging.
AB  - Femtosecond time-resolved photoelectron imaging (TRPEI) is a variant of time
      resolved photoelectron spectroscopy used in the study of gas-phase photoinduced
      dynamics. A new observable, time-dependent photoionization-differential cross
      section provides useful information on wave-packet motions, electronic dephasing,
      and photoionization dynamics. This review describes fundamental issues and the
      most recent works involving TRPEI.

PMID- 16599820
TI  - Raman crystallography and other biochemical applications of Raman microscopy.
AB  - Recent studies using a Raman microscope have shown that single protein crystals
      provide an ideal platform to undertake Raman difference spectroscopic analyses
      under nonresonance conditions. This approach, termed Raman crystallography,
      provides a means of characterizing chemical events within the crystal such as
      ligand binding and enzyme reactions. In many cases Raman crystallography goes
      hand in hand with X-ray crystallographic studies because the Raman results can
      inform the X-ray crystallographer about the status of chemical events in the
      crystal prior to flash freezing and X-ray analysis. In turn, the combined data
      from the Raman and X-ray analyses are highly synergistic and offer novel
      perspectives on structure and dynamics in enzyme active sites. In a related area,
      protein misfolding, Raman microscopy can provide detailed insights into the
      chemistry of the amyloid plaques associated with Alzheimer's disease and into the
      intermediates on the alpha-synuclein protein misfolding pathway implicated in
      Parkinson's disease.

PMID- 16599822
TI  - Single-molecule electrical junctions.
AB  - The objective of this review is to describe current experimental research of
      single-molecule electrical junctions in the context of various theoretical
      frameworks, with emphasis on the application of single-electron transistor theory
      to molecular junctions. Molecule quantum dots are at least an order of magnitude
      smaller than semiconductor quantum dots, which allows the study of many of the
      same mesoscopic and many-body effects at far higher temperatures. We discuss
      processes such as cotunneling, sequential tunneling, and incoherent tunneling, as
      well as the Kondo effect, Zeeman splitting, and the Coulomb diamond. Goals for
      future experimental work are outlined.

PMID- 16599823
TI  - Dynamical studies of the ozone isotope effect: A status report.
AB  - Dynamical studies of the recombination of O and O2 to form ozone are reviewed.
      The focus is the intriguing isotope dependence of the recombination rate
      coefficient as observed by Mauersberger and coworkers in the last decade. The key
      quantity for understanding of this dependence appears to be the difference of
      zero-point energies of the two fragmentation channels to which excited ozone can
      dissociate, i.e., X + YZ <-- XYZ* --> XY + Z, where X, Y, and Z stand for the
      three isotopes of oxygen. Besides the isotope dependence, the variation of the
      recombination rate coefficient with pressure and temperature is also addressed.
      Despite the numerous approaches of recent years, the recombination of ozone is
      far from being satisfactorily explained; there are still several essential
      questions to be solved by detailed theoretical analysis. We mainly discuss--and
      critically assess--the results of our own investigations of the ozone kinetics.
      The work of other research groups is also evaluated.

PMID- 16599825
TI  - Natriuretic peptides and evidence-based quality specifications.

PMID- 16599826
TI  - Preanalytical variability: the dark side of the moon in laboratory testing.
AB  - Remarkable advances in instrument technology, automation and computer science
      have greatly simplified many aspects of previously tedious tasks in laboratory
      diagnostics, creating a greater volume of routine work, and significantly
      improving the quality of results of laboratory testing. Following the development
      and successful implementation of high-quality analytical standards, analytical
      errors are no longer the main factor influencing the reliability and clinical
      utilization of laboratory diagnostics. Therefore, additional sources of variation
      in the entire laboratory testing process should become the focus for further and
      necessary quality improvements. Errors occurring within the extra-analytical
      phases are still the prevailing source of concern. Accordingly, lack of
      standardized procedures for sample collection, including patient preparation,
      specimen acquisition, handling and storage, account for up to 93% of the errors
      currently encountered within the entire diagnostic process. The profound
      awareness that complete elimination of laboratory testing errors is unrealistic,
      especially those relating to extra-analytical phases that are harder to control,
      highlights the importance of good laboratory practice and compliance with the new
      accreditation standards, which encompass the adoption of suitable strategies for
      error prevention, tracking and reduction, including process redesign, the use of
      extra-analytical specifications and improved communication among caregivers.

PMID- 16599827
TI  - Clinical relevance of biological variation: the lesson of brain natriuretic
      peptide (BNP) and NT-proBNP assay.
AB  - The clinical relevance of brain natriuretic peptide (BNP) and N-terminal (NT)
      proBNP assays as a diagnostic tool and prognostic marker in patients with
      cardiovascular diseases has recently been confirmed. However, several studies
      demonstrated variation of intra-individual BNP concentrations of >30% (ranging
      from 30% to 50%) with reference change values at the 95% confidence interval
      (i.e., the estimated critical difference) ranging from 99% to 130% in healthy
      subjects and heart failure patients. According to this estimated confidence
      interval, only a great variation in plasma BNP levels should be considered
      significant in an individual patient (for example, a decrease of >50% or an
      increase of more than two-fold). Many recent clinical studies have demonstrated
      that BNP variations below this estimated critical difference could also have
      clinical relevance. Like the concentration of other neuro-hormones, levels of
      plasma BNP fluctuate widely and rapidly along with heart rhythm and blood
      pressure variations in response to physiological stimuli. However, biological
      variation of BNP should not be interpreted strictly as random fluctuation around
      a homeostatic set point, as assumed by the common model used in all studies on
      biological variation of BNP reported in the literature. These results cannot be
      directly transferred to clinical practice. While awaiting more accurate studies,
      we suggest that variations of plasma BNP three-fold greater than the analytical
      imprecision should be considered as potentially relevant from a physiological and
      clinical point of view.

PMID- 16599828
TI  - Hepatorenal syndrome.
AB  - This article summarizes the literature on current definition, suggested
      pathogenetic mechanisms and the role of laboratory assessment in the differential
      diagnosis of hepatorenal syndrome (HRS) from other causes of renal disease that
      may arise during hepatic cirrhosis and some diseases affecting both liver and
      kidney. It should be remembered that the main theory suggested for the
      pathogenesis of HRS is the arterial vasodilation hypothesis of portal
      hypertension, ending in type 1 and type 2 HRS, but there is no consensus
      supporting either mechanism as a solid theory for initiation of HRS pathogenesis
      to date. No laboratory test can firmly establish a diagnosis of HRS, which is
      mainly based on the absence of any specific cause of renal failure. Laboratory
      and ultrasonographic tests based on non-invasive techniques are being
      investigated as possible diagnostic approaches.

PMID- 16599829
TI  - Modified Levey-Jennings charts for calculated laboratory tests.
AB  - BACKGROUND: In clinical laboratories, many test results such as low-density
      lipoproteins can be calculated using the results of specifically measured tests.
      However, quality control programs deal with only measured tests and there is no
      quality control procedure for calculated tests. I aimed to modify the Levey
      Jennings chart for calculated tests as part of a total quality system. METHODS: I
      developed a method using a Taylor series expansion and alternative equations to
      obtain the standard deviation of calculated tests and then prepared Levey
      Jennings charts for these tests. RESULTS: Preparation of Levey-Jennings charts
      for low-density lipoproteins (and other calculated tests) was simple, and using
      this chart increased the reliability of calculated test results. CONCLUSION:
      Checking only measured tests by quality control procedures before reporting
      patient results may be inadequate. Preparation of Levey-Jennings charts for
      calculated tests as part of total quality management will increase the
      reliability of test results.

PMID- 16599830
TI  - Increased free malondialdehyde concentrations in smokers normalise with a mixed
      fruit and vegetable juice concentrate: a pilot study.
AB  - BACKGROUND: Cigarette smoking, a cardiovascular risk factor leading to oxygen
      free radical formation, is involved in the development of serious pathological
      conditions. On the other hand, a healthy diet and adequate supplementation can
      help prevent many diseases. The aim of our study was to evaluate in healthy light
      smokers the effects of supplementation with mixed fruit and vegetable juice
      powder concentrate on homocysteine metabolism and oxidative status. METHODS: In
      this pilot study, 32 healthy volunteers, 16 light smokers and 16 non-smokers, on
      twice daily supplementation were monitored at time zero and after 30 days. Plasma
      homocysteine, and serum vitamin B(12) and folate concentrations were measured by
      immunoenzymatic assays; reactive oxygen species, total antioxidant capacity and
      thiol groups by spectrophotometric methods; and total and free malondialdehyde
      concentrations by gas chromatography-mass spectrometry with isotopic dilution.
      RESULTS: Baseline free malondialdehyde concentrations were significantly higher
      in smokers than in non-smokers and normalised after 30-day supplementation.
      Baseline results for all the other parameters remained unchanged after
      supplementation, with no significant differences between smokers and non-smokers.
      CONCLUSION: This is the first study showing a significant decrease in free
      malondialdehyde levels in light smokers after 1-month phytonutrient
      supplementation.

PMID- 16599831
TI  - The exponentially weighted moving average (EWMA) rule compared with traditionally
      used quality control rules.
AB  - BACKGROUND: The exponentially moving average (EWMA) rule for internal quality
      control is a well-known type of control rule in industry. Here, the power of the
      EWMA rule is evaluated to outline the potential of this type of control rule in
      clinical chemistry. METHODS: Using simulations, the power of the EWMA rule was
      explicitly compared with that of commonly used rules in clinical chemistry. The
      type I error levels were standardized to common values to achieve unbiased
      comparisons. RESULTS: For small to moderately large errors (systematic errors up
      to 2-3 standard deviations), the EWMA rule outperforms simple rules (N=1) and
      multi-rules (N=2-6). For example, for a systematic error of 2s, the EWMA rule
      equivalent to the 1(3s) rule has a power of 0.30, whereas the 1(3s) rule only
      displays a power of approximately 0.15. For N=4, comparison was carried out with
      the 1(3s)/2(2s)/R(4s)/4(1s) rule. Here the common type I error level is 0.017. At
      all error levels, the EWMA rule is superior to the multi-rule. For example, given
      a 1s systematic error, the EWMA rule has a power (0.4) of twice the value of the
      multi-rule (0.2). CONCLUSION: The EWMA rule is an efficient control rule with
      regard to systematic errors that should be considered for general application in
      the field of clinical chemistry.

PMID- 16599832
TI  - Intermethod calibration of alanine aminotransferase (ALT) and gamma
      glutamyltransferase (GGT) results: application to Fibrotest and Actitest scores.
AB  - Two multi-component scores (Fibrotest and Actitest) have been proposed to
      evaluate liver fibrosis or necro-inflammatory lesions as an alternative to liver
      biopsy. This approach requires standardization of alanine aminotransferase (ALT)
      and gamma-glutamyltransferase (GGT) determinations. For this purpose, ALT and GGT
      values were assigned to a multi-enzyme material using the appropriate primary
      reference procedure. This material was used as a common calibrator for sera from
      20 patients with viral hepatitis. Measurements were carried out in 11
      laboratories, using their own automated routine methods and compared to results
      obtained using the primary reference procedure. The expression of results in
      multiples of the upper reference limit worsened the inter-laboratory variation
      for both enzymes. The multi-enzyme material was commutable for ALT and GGT
      determination carried out with six analytical systems. Common calibration
      significantly improved inter-laboratory consistency, which finally reached 1.8%
      and 3.3% for ALT and GGT, respectively. For each enzyme, it also permitted the
      retention of a common reference interval for a set of calibrated methods and the
      improvement of inter-laboratory coherency of Fibrotest and Actitest scores.

PMID- 16599833
TI  - Comparison of TEST 1 with SRS 100 and ICSH reference method for the measurement
      of the length of sedimentation reaction in blood.
AB  - BACKGROUND: We evaluated the measurement of length of sedimentation reaction in
      blood (LSRB) by TEST 1 and compared the results with those for the Westergren and
      Sed Rate Screener 100 (SRS 100) methods. METHODS: LSRB was measured in 113 paired
      blood samples. RESULTS: TEST 1 correlated significantly with the Westergren
      (r=0.94) and SRS 100 (r=0.90) methods with low bias (-0.29 and -1.92 mm/h,
      respectively) and limits of agreement (-14.5 to 13.9, and -23.4 to 19.6 mm/h,
      respectively). Hematocrit (Htc) correlated negatively with LSRB in TEST 1 (r=
      0.54) and SRS 100 (r=-0.53) only in samples with high Htc (>/=35%). The bias and
      limits of agreement between TEST 1 and Westergren in samples with low (-1.46 and 
      22.3 to 19.3 mm/h) and high (0.43 and -7.29 to 8.14 mm/h) Htc were comparable to
      those between SRS 100 and Westergren (1.83 and -27.2 to 30.9 mm/h for low, 0.71
      and -7.27 to 8.70 mm/h for high Htc samples). Total protein and fibrinogen
      correlated similarly with LSRB in both TEST 1 (r=0.23 and 0.48, respectively) and
      SRS 100 (r=0.30 and 0.51, respectively). CONCLUSIONS: The findings suggested that
      TEST 1 is a reliable, precise and accurate system for measurement of LSRB in
      clinical laboratories with high workload.

PMID- 16599834
TI  - Multicenter evaluation of the interference of hemoglobin, bilirubin and lipids on
      Synchron LX-20 assays.
AB  - The influence of interference by hemolysis, icterus and lipemia on the results of
      routine chemistries may lead to wrong interpretations. The H-, I- and L-indices
      that can be measured by the Beckman LX-20 instrument (Beckman Coulter) in serum
      or plasma samples are a reliable semi-quantitative measure of the size of these
      interferences. A survey carried out in 16 Dutch clinical laboratories on the use
      of these indices demonstrated that in several of these laboratories, the
      influence of interferences is largely underestimated. Therefore, a multicenter
      study was carried out in which we examined the interference of hemolysis, icterus
      and lipemia on 32 analytes. On the basis of biological variation, we decided on
      cutoff indices above which analytically significant interference exists. We found
      analytically significant interference by hemolysis, icterus or lipemia, in 12, 7
      and 15 of the 32 analytes studied, respectively. Flagging of results on the basis
      of analytically significant interference, however, results in too many clinically
      insignificant comments. On the basis of clinical significance, we conclude that
      significant interference by hemolysis, icterus or lipemia is present in only 5, 6
      and 12 of the analytes studied, respectively. Use of the cutoff indices presented
      here facilitates optimal use of the LX-20 indices to prevent reporting of wrong
      results due to interference.

PMID- 16599835
TI  - Technical evaluation of the Beckman Coulter OV-Monitor (CA 125 antigen)
      immunoassay.
AB  - BACKGROUND: The CA 125 antigen is a large (200-1000 kDa) glycoprotein, present
      within normal and benign ovarian tissue. We evaluated the analytical performance
      of the newly available Beckman Coulter OV-Monitor (CA 125 antigen) immunoassay on
      the Beckman Coulter UniCel DxI 800 analyzer. METHODS: The evaluation was
      performed according to NCCLS recommendations. RESULTS: The lowest level of CA 125
      antigen detectable was 0.374 U/mL. Serial dilution of two pooled CA 125 antigen
      rich samples provided a linear response (p<0.0001). For total CV% the following
      results were obtained: pool sera, 11.7 U/mL (2.70%), 56.3 U/mL (2.41%), 108.43
      U/mL (2.31%); and QC sera, 29.4 U/mL (2.57%), 101.1 U/mL (3.26%). Comparison of
      the OV-Monitor on the UniCel DxI 800 showed linear regression values of r=0.961
      vs. the Bayer ADVIA Centaur system and r=0.981 vs. the Abbott AxSYM system.
      CONCLUSION: Considering the limited number of serum samples analyzed, our data
      indicate that the Beckman Coulter OV-Monitor immunoassay has excellent analytical
      performance and shows satisfactory correlation with automated immunoassays on the
      Abbott AxSYM and Bayer ADVIA Centaur systems. It is easy to perform, accurate and
      suitable for measurements in routine clinical laboratories.

PMID- 16599836
TI  - Erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase activities in subjects with
      methylenetetrahydrofolate reductase (MTHFR) 677 C-->T genotype and moderate
      hyperhomocysteinaemia. The role of L-phenylalanine and L-alanine.
AB  - BACKGROUND: Increased homocysteine (Hcy) blood levels are correlated with
      vascular and neurological problems. The aim of our study was to investigate
      erythrocyte membrane Na(+),K(+)-ATPase and Mg(2+)-ATPase activities in patients
      with methylenetetrahydrofolate reductase (MTHFR) 677 C-->T genotype. METHODS:
      Blood was obtained from 25 patients before and after folic acid supplementation
      and from controls (n=30) once. Plasma folate, vitamin B(12) and total antioxidant
      status (TAS) were measured using commercial kits, Hcy was determined by HPLC and
      membrane enzyme activities were measured spectrophotometrically. RESULTS: Mg(2+)
      ATPase remained unaltered. Membrane Na(+),K(+)-ATPase activity was remarkably
      increased in patients (0.77+/-0.06 micromol Pi/h x mg protein) and decreased to
      normal levels (0.52+/-0.05 micromol Pi/h x mg protein; p<0.001) after therapy.
      TAS did not differ significantly before and after treatment. Hcy levels were
      significantly higher before therapy (25.4+/-2.8 micromol/L) than levels after
      therapy (12.1+/-2.0 micromol/L; p<0.001) and in controls (10.5+/-2.5 micromol/L,
      p<0.001). In vitro, L-phenylalanine (Phe) reversed to normal the stimulated
      enzyme from patients before therapy. In addition, Phe incubation of the Hcy
      activated membrane Na(+),K(+)-ATPase from controls resulted in restoration of its
      activity, whereas L-alanine (Ala) incubation protected the enzyme from Hcy
      activation. CONCLUSIONS: The increased membrane Na(+),K(+)-ATPase activity may be
      due to high -SH group Hcy levels. In vitro, Phe reversed the increase in enzyme
      activity induced by Hcy in controls, as well as the stimulated membrane enzyme in
      untreated patients. Ala protected the enzyme from Hcy action.

PMID- 16599837
TI  - Matrix metalloproteinases and their inhibitors in different acute stroke
      subtypes.
AB  - The aim of the study was to determine serum levels of selected matrix
      metalloproteinases (MMPs) and their natural inhibitors (TIMPs) in the acute phase
      of different stroke types subdivided according to the Oxfordshire Community
      Stroke Project (OCSP) classification and the possibility of discriminating stroke
      types according to their levels. The study included 126 patients with acute
      stroke within the first 24 h of symptom onset, and 124 healthy volunteers. The
      stroke group had lower MMP-2 concentrations and MMP-2/TIMP-2 ratios (p<0.001) but
      higher TIMP-2 (p<0.001) than controls. The level of MMP-9 and the MMP-9/TIMP-1
      ratio were higher in patients with total anterior circulation infarct (TACI) than
      in patients with other stroke subtypes according to OCSP classification
      (p=0.0019, p=0.0065, respectively) or in controls (p<0.0001, p=0.0024,
      respectively). A negative correlation of MMP-2 levels with MMP-9 and MMP-9/TIMP-1
      ratio was recorded in all stroke subtypes except for TACI. Receiver operating
      characteristic analysis showed similar discriminating power for MMP-9 levels and
      Barthel index in the differential diagnosis of TACI. High MMP-9/TIMP-1 ratio
      (odds ratio 3.263) was associated with TACI. Our results demonstrate that the MMP
      9/TIMP-1 ratio may provide information to help in assessing stroke patients in
      the future as a baseline biomarker of infarct extent.

PMID- 16599838
TI  - Pyrosequencing protocol requiring a unique biotinylated primer.
AB  - BACKGROUND: DNA sequencing has markedly changed the nature of biomedical
      research. Large-scale sequencing projects have generated several millions of
      potential polymorphisms widespread in the human genome requiring validation and
      incorporation into screening panels. As a consequence, high-throughput analysis
      of these variants in different populations of interest is now the cornerstone of
      structural genomics. Pyrosequencing is a versatile technique allowing an easy 96
      well typing format. However, every polymorphism requires a specific labeled
      primer to generate a single-stranded DNA fragment containing the region of
      interest. METHODS: We describe how with an adjusted primer stoichiometry we can
      standardize the labeling of every amplicon with a single biotinylated universal
      primer (BM13S). RESULTS: We circumvent the need for specific biotinylated primers
      for each single-nucleotide polymorphism (SNP) under study. As an example, we
      assessed this novel protocol by genotyping three SNPs mapping calpain-10,
      caveolin-1 and CYP19A1. CONCLUSION: The present approach represents an
      alternative to standard pyrosequencing protocols, since it requires a single
      biotinylated primer that is suitable for each SNP under study.

PMID- 16599839
TI  - Detection of antibodies against 60-, 65- and 70-kDa heat shock proteins in
      paediatric patients with various disorders using Western blotting and ELISA.
AB  - BACKGROUND: We examined antibodies against 60-, 65- and 70-kDa heat shock
      proteins (HSPs) in paediatric healthy individuals, patients with juvenile
      idiopathic arthritis (JIA) and those undergoing allogeneic stem-cell
      transplantation for various malignant and non-malignant diseases. METHODS:
      Western blotting and ELISA were used to examine HSP-directed humoral immune
      responses. RESULTS: Using ELISA we detected anti-Hsp60, -Hsp65 and -Hsp70 IgG
      antibodies in patient sera before, during and after conditioning and at all post
      transplant times, as well as in JIA patients and controls. Western blotting
      showed positivity for anti-Hsp60 and anti-Hsp65 antibodies in all samples with a
      HSP concentration of 0.5 microg/lane. However, anti-Hsp70 antibodies were not
      detected at all when both sodium dodecyl sulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) and native PAGE were used, except for one JIA patient,
      for whom a positive signal was only achieved in native PAGE when Hsp70 was
      increased to 2 microg/lane and serum dilution decreased to 1:10. CONCLUSION:
      Western blotting is convenient for the detection of anti-Hsp60 and anti-Hsp65
      antibodies, but it is not sensitive enough for the detection of anti-Hsp70
      antibodies. ELISA, which is more sensitive, might be preferentially used to
      screen anti-Hsp60, -Hsp65 and -Hsp70 antibodies in sera of children with various
      disorders.

PMID- 16599841
TI  - Time-level relationship between indicators of oxidative stress and Glasgow Coma
      Scale scores of severe head injury patients.
AB  - BACKGROUND: Oxidative stress is said to strongly influence the neurological
      recovery of patients following a severe head injury. Estimation of the markers of
      oxidative stress in the blood of such patients can hence aid in predicting the
      prognosis of head injury. METHODS: Erythrocyte thiobarbituric acid-reactive
      substances (TBARS) and plasma ceruloplasmin (CP) levels were estimated in 24
      severe head-injury patients on days 1, 7 and 21 of the post-traumatic period and
      compared with levels in 25 healthy age- and sex-matched controls. These
      parameters reflecting oxidative stress status were related to the Glasgow Coma
      Scale (GCS) scores of patients noted at the same time points of the study period.
      RESULTS: Lipid peroxidation as indicated by increased levels of erythrocyte TBARS
      remained significantly elevated in severe head injury patients compared to
      controls on day 1 (p<0.001), day 7 (p<0.001) and 21 (p<0.001) of the post
      traumatic period. Plasma CP levels remained significantly elevated (p<0.001) at
      these three time points compared to controls. The significant decrease in lipid
      peroxidation products (p<0.01) and significant increase in CP levels (p<0.001) on
      day 21 compared to day 1 in head injury patients correlated well with the
      significant improvement in GCS scores of patients on day 21 compared to day 1
      (p<0.05). CONCLUSION: The above results could account for the adaptation of the
      study patients to severe oxidative stress, as evidenced by their clinical
      recovery trend during the study period.

PMID- 16599840
TI  - Quantitative determination of erythrocyte folate vitamer distribution by liquid
      chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Given the role of folate in many disorders, intracellular
      distribution of folate vitamers is of potential clinical importance. In
      particular, accumulation of non-methyltetrahydrofolates due to altered
      partitioning of folate metabolism at the level of methylenetetrahydrofolate is of
      interest. METHODS: We describe a positive-electrospray liquid chromatography
      tandem mass spectrometry (LC-MS/MS) method that allows determination of
      erythrocyte folate vitamer distribution by accurately measuring both 5
      methyltetrahydrofolate (5-methylTHF) and non-methyl folate vitamers. Whole blood
      lysates are deconjugated in ascorbic acid solutions, deproteinized, purified
      using folate-binding protein affinity columns, concentrated by solid-phase
      extraction (SPE) and evaporation, and separated on a C18 column within 6 min.
      RESULTS: The limit of quantification for both 5-methylTHF and non-methylTHF was
      0.4 nmol/L (signal-to-noise >10). Intra- and inter-assay CVs for 5-methylTHF were
      1.2% and 2.8%, respectively. Intra- and inter-assay CVs for non-methylTHF as a
      group were 1.6% and 1.5%, respectively. Recovery results were 97-107%. We
      measured 8-72% non-methyl folate vitamers in volunteers (n=5) with the
      methylenetetrahydrofolate reductase (MTHFR) 677 TT genotype. Concentrations
      ranged from 117 to 327 nmol/L and 23 to 363 nmol/L for 5-methylTHF and non
      methylTHF vitamers, respectively. We measured 0-2% non-methylTHF vitamers in
      MTHFR 677 CC genotype volunteers. In addition, we found that storage of whole
      blood samples in ascorbic acid at low pH resulted in 53-90% loss of the non
      methylTHF fraction. CONCLUSION: This LC-MS/MS method accurately determines
      erythrocyte 5-methylTHF and non-methyl folate vitamers.

PMID- 16599842
TI  - Stepwise strategies in analysing haematuria and leukocyturia in screening.
AB  - The aim of the present work was to compare in a supposed healthy population of
      680 subjects several algorithms for positive selection of urine samples requiring
      microscopic examination for erythrocytes and leukocytes after screening by
      automated test-strip measurement and particle counting on a Sysmex UF-50 flow
      cytometer. Four strategies have been formulated and the sensitivity, specificity,
      positive predictive value, negative predictive value, false positive rate, false
      negative rate, and microscopic review rate were measured. The strategy combining
      test strip analysis and automated counting on all samples, followed by
      microscopic examination of only discordant samples gave the best results. When
      the two methods of haematuria screening were in agreement (91% of samples), the
      false negative rate for microscopy was 1.1%, with a false positive rate of 0.8%,
      sensitivity of 66% and specificity of 99%, and the results are acceptable without
      any other examination. When the two methods of haematuria screening were
      discrepant, visual microscopic analysis was necessary to obtain definitive
      results. For leukocyturia screening, 80% of results were in agreement by test
      strip and automatic sediment urinalysis, with only ten results considered as
      false negatives (1.8%) and four as false positives (0.7%). Agreement was good and
      the other criteria were good (sensitivity 79%, specificity 99%). On conflicting
      samples, there was no agreement between methods and microscopic analysis was
      essential. The benefit of such an algorithm would be optimisation of the workflow
      without any loss of sensitivity and specificity at the expense of a two-fold
      increase in cost.

PMID- 16599843
TI  - Elevation of serum cerebral injury markers correlates with serum choline decline
      after coronary artery bypass grafting surgery.
AB  - The aims of this study were to determine circulating choline status and its
      relationship to circulating levels of S-100beta protein and neuron-specific
      enolase, biochemical markers of cerebral injury and cognitive decline, after
      coronary artery bypass grafting (CABG) surgery. Preoperatively, patients
      scheduled for off-pump or on-pump CABG surgery had serum concentrations of 12.0+/
      0.2 and 11.7+/-0.4 micromol/L free choline and 2640+/-65 and 2675+/-115
      micromol/L phospholipid-bound choline, respectively. Serum free and bound choline
      levels decreased by 22-37% or 34-47% and 16-36% or 31-38% at 48 h after off-pump
      or on-pump surgery, respectively. Serum S-100beta and neuron-specific enolase
      increased from preoperative values of 0.083+/-0.009 and 6.3+/-0.2 microg/L to
      0.405+/-0.022 and 11.4+/-0.8 microg/L, respectively, at 0 h postoperatively and
      remained elevated for 48 h after off-pump surgery. Serum free and bound choline
      concentrations were inversely correlated with the concentrations of S-100beta (r=
      0.798; p<0.001 and r=-0.734; p<0.001) and neuron-specific enolase (r=-0.840;
      p<0.001 and r=-0.728; p<0.001). In conclusion, CABG surgery induces a decline in
      serum free and phospholipid-bound choline concentrations. The decreased serum
      choline concentrations were inversely correlated with the elevated levels of
      circulating cerebral injury markers. Thus, a decline in circulating choline may
      be involved in postoperative cognitive decline.

PMID- 16599844
TI  - Drug screening in urine by cloned enzyme donor immunoassay (CEDIA) and kinetic
      interaction of microparticles in solution (KIMS): a comparative study.
AB  - Two commercially available drug-screening assays were evaluated: the Roche
      kinetic interaction of microparticles in solution (KIMS) assay and the
      Microgenics cloned enzyme donor immunoassay (CEDIA). Urine samples from known
      drug-abuse patients were analyzed for amphetamines, barbiturates,
      benzodiazepines, benzoylecgonine, cannabinoids, LSD, methadone and opiates.
      Samples with discordant findings for the two assays were analyzed by gas
      chromatography/mass spectrometry (GC/MS) or gas chromatography/electron capture
      detection (GC/ECD). Amphetamines showed 96.0% concordant results, with two false
      positive findings by CEDIA, three by KIMS and a further two false negatives by
      KIMS. Barbiturates showed 99.4% concordant results, with one false negative by
      KIMS. Benzodiazepines showed 97.4% concordant results, with two false negatives
      by KIMS (cutoff 100 microg/L, CEDIA cutoff 300 microg/L). Benzoylecgonine showed
      17.8% concordant positive and 82.2% concordant negative results and no false
      finding by either assay. Cannabinoids showed 99.3% concordant results, with one
      sample negative by KIMS at a cutoff of 50 microg/L and positive by CEDIA (cutoff
      25 microg/L). For LSD, 6.7% of findings were not in agreement. Methadone showed
      97.5% concordant results, with two false positives by CEDIA, and one false
      positive and one false negative by KIMS. Opiates showed 96.9% concordant results,
      with no false KIMS results, but four false positives by CEDIA. The results
      indicate that the agreement of the CEDIA and KIMS results for the eight drugs is
      rather good (93.3-100%).

PMID- 16599845
TI  - Release of anandamide from blood cells.
AB  - BACKGROUND: Endogenous ligands of cannabinoid receptors (endocannabinoids), in
      particular anandamide (arachidonylethanolamide), have been recognized as being of
      crucial importance in a variety of physiological functions. Plasma concentrations
      of anandamide have been measured in a number of investigations; however,
      discrepant data on "normal" anandamide plasma concentrations were reported. Since
      this might be caused by pre-analytical variables, we investigated the impact of
      different sample handling conditions on measured plasma anandamide
      concentrations. METHODS: Blood samples were taken from healthy volunteers in EDTA
      or heparin-containing tubes; whole blood samples were kept at +4 degrees C, room
      temperature, or 37 degrees C, respectively, for up to 120 min before obtaining
      plasma by centrifugation. Plasma anandamide concentrations were measured by an
      isotope-dilution liquid chromatography tandem mass spectrometry (LC-MS/MS)
      method. RESULTS: A marked time- and temperature-dependent increase in plasma
      anandamide concentrations ex vivo was observed in both EDTA- and heparin
      containing tubes. Mean anandamide concentrations approximately doubled when EDTA
      samples were kept at 4 degrees C for 60 min before centrifugation [immediately
      centrifuged, 1.3 microg/L (SD 0.3 microg/L); 2.8 microg/L (SD 0.5 microg/L) after
      storage for 60 min; n=12). After storage of heparinized whole-blood samples for
      120 min at 37 degrees C, a mean plasma anandamide concentration of 11.9 microg/L
      (SD 1.8 microg/L) was found. In cell-free plasma, no increase in anandamide
      concentrations was found. CONCLUSION: Anandamide is released from blood cells ex
      vivo at a very high rate; therefore, strictly standardized pre-analytical
      protocols have to be applied for plasma anandamide determination.

PMID- 16599846
TI  - Rapid decrease in plasma D-lactate as an early potential predictor of diminished
      28-day mortality in critically ill septic shock patients.
AB  - BACKGROUND: Splanchnic ischemia plays a major role in the development of organ
      failure during septic shock. Plasma D-lactate has been proposed as a better
      marker of splanchnic hypoperfusion than L-lactate. We studied the prognostic
      ability of plasma D- and L-lactate levels. METHODS: A prospective study was
      performed in an intensive care unit and included patients with septic shock. Two
      samples for plasma D- and L-lactate determination were collected: the first
      within 6 h after the patient met the criteria for septic shock (day 1) and the
      second 24 h later (day 2). RESULTS: In univariate analysis, day 1 plasma D- and L
      lactate values were associated with 28-day mortality. For plasma D- and L-
      lactate, the area under the receiver operating characteristic curve was 0.68+/
      0.09 and 0.84+/-0.07 on day 1 (p=0.09), and 0.74+/-0.10 and 0.90+/-0.07 on day 2
      (p=0.06), respectively. In survivors, D-lactate levels decreased between day 1
      and day 2 (p=0.03), but L-lactate did not (p=0.29). In septic shock patients,
      plasma D- and L-lactate levels reliably discriminate between survivors and non
      survivors. The prognostic ability of plasma L-lactate was better than that of
      plasma D-lactate. CONCLUSION: A rapid decrease in plasma D-lactate during the
      course of septic shock could indicate reduced 28-day mortality.

PMID- 16599847
TI  - Evaluation of an immunoassay of whole blood sirolimus in pediatric transplant
      patients in comparison with high-performance liquid chromatography/tandem mass
      spectrometry.
AB  - BACKGROUND: Sirolimus is widely used as an immunosuppressant, along with
      calcineurin inhibitors. Because of its variable pharmacokinetics and narrow
      therapeutic range, therapeutic drug monitoring of sirolimus is critical to
      optimize its therapeutic effect and to minimize toxicity. Although liquid
      chromatography/tandem mass spectrometry is considered the method of choice, the
      technical and financial challenges of this method are obstacles to its use. A
      microparticle enzyme immunoassay on the Abbott IMx has recently been reintroduced
      to the clinical diagnostic market. METHODS: We evaluated this immunoassay using
      high-performance liquid chromatography/tandem mass spectrometry as the reference
      method. Precision and carryover were evaluated using an expanded CLSI EP10-A2
      protocol. Linearity was studied by serial dilution of high-level whole blood
      samples, and clinical utility was demonstrated by correlation with the reference
      method using 56 de-identified pediatric patient samples. RESULTS: The total
      imprecision was less than 12% across the concentrations tested. The method was
      linear from 2.6 to 31 nM. The immunoassay showed a mean positive bias of 11.5% in
      patient specimens relative to high-performance liquid chromatography/mass
      spectrometry (p<0.001), with a correlation coefficient (R) of 0.953. CONCLUSION:
      We conclude that the reintroduced immunoassay is useful for therapeutic drug
      monitoring of sirolimus.

PMID- 16599848
TI  - Sample processing and its preanalytical impact on the measurement of circulating
      matrix metalloproteinases.

PMID- 16599849
TI  - Physiological matrix metalloproteinase (MMP) concentrations: comparison of serum
      and plasma specimens.

PMID- 16599850
TI  - Importance of the functional sensitivity determination of a serum hyaluronic acid
      assay for the prediction of liver fibrosis in patients with features of the
      metabolic syndrome.

PMID- 16599851
TI  - The dilemma of invasive and non-invasive investigations for adult and paediatric
      non-alcoholic fatty liver disease: has the time come for a new biochemical
      marker?

PMID- 16599852
TI  - Is cystatin C a reliable renal marker in trauma?

PMID- 16599853
TI  - On the independence of intraindividual reference values.

PMID- 16599854
TI  - Learning to live with meta-analysis.

PMID- 16599855
TI  - Critical care and resuscitation: we hit the ground running.

PMID- 16599856
TI  - Standards for resuscitation - can we avoid the "Inertia of tradition"?

PMID- 16599857
TI  - Issues of withdrawal of therapy and brain death in paediatric intensive care.

PMID- 16599858
TI  - The Australasian Academy of Critical Care Medicine.

PMID- 16599859
TI  - Renal replacement therapy in the intensive care unit.
AB  - OBJECTIVE: To present an overview of the principles of renal replacement therapy,
      its application in the critically ill patient, and an update of recent research
      in this area. DATA SOURCES: Articles and published peer-review abstracts on the
      beneficial effects of continuous renal replacement therapy (CCRT) in the
      critically ill patient. SUMMARY OF REVIEW: Renal replacement therapy utilizes
      dialysers that enable solute and solvent to move across semipermeable membranes
      in either a convective or diffusive fashion. In the critically ill patient,
      percutaneous vascular access and improvement in dialysis machines, have
      facilitated the intensive care unit management of acute renal failure in these
      patients. Currently, CCRT is most often used to manage the critically ill patient
      with acute renal failure, as it is less likely to produce hypotension when
      compared with intermittent haemodialysis. However, CCRT has been expanded to
      manage critically ill patients with multiple organ failure, with the
      demonstration that it is able to remove or adsorb putative mediators of organ
      dysfunction. While there are experimental and uncontrolled clinical data that
      have suggested that this form of therapy is beneficial, currently there are no
      prospective randomised, controlled trials that have confirmed this benefit when
      used in these patients. CONCLUSIONS: Continuous renal replacement therapy has
      become commonplace in the management of critically ill patients with acute renal
      failure. It has the advantage of causing less hypotension and a more gradual
      return of the fluid and electrolyte status, when compared with intermittent
      haemodialysis. Recent evidence suggests that it may also be a useful
      immunomodulator and may be beneficial in the management of patients with multiple
      organ failure.

PMID- 16599860
TI  - Acute liver failure.
AB  - OBJECTIVE: To consider the classification and to present an approach to the
      diagnosis and management of complications associated with acute liver failure.
      DATA SOURCES: A review of studies reported from 1966 to 1998 and identified
      through a MEDLINE search on treatment of acute liver failure. SUMMARY OF REVIEW:
      Acute liver failure can be subdivided into hyperacute, (encephalopathy within 7
      days of onset of jaundice) acute (8-28 days from jaundice to encephalopathy) and
      subacute (29 to 72 days from jaundice to encephalopathy) forms. Management of all
      forms involves largely supportive care until hepatocyte regeneration and recovery
      occurs (predominantly in the hyperacute group), or bridging supportive therapy
      until orthotopic liver transplantation can be performed. New therapies such as
      bioartificial liver support devices and ex-vivo liver perfusion offer exciting
      possibilities for this bridging therapy. While orthotopic liver transplantation
      remains the definitive treatment for many patients with acute liver failure, N
      acetyl-cystine (150 mg/kg over 15 minutes followed by 12.5 mg/kg/hour) and PGE(1)
      (10 - 40 microg/hour) are reported to have an additional role and are being used
      increasingly in the management of all forms of acute liver failure. CONCLUSIONS:
      Acute liver failure is the end stage of many acute viral and drug induced hepatic
      diseases. Management is largely supportive until hepatic repair or
      transplantation can be performed. Recently, additional hepatic protective,
      regenerative and supportive therapies have been successfully used.

PMID- 16599861
TI  - Gastric emptying in the critically ill patient.
AB  - OBJECTIVE: To review the pathophysiology of gastroparesis and present a practical
      approach to the management of this disorder in the critically ill patient. DATA
      SOURCES: Articles and published abstracts on the mechanisms and management
      gastroparesis relevant to the critically ill patient. SUMMARY OF REVIEW: The
      importance of early enteral nutrition in the critically ill patient has been
      recognised for many years. However, while nasogastric tubes are easy to insert,
      gastric dysmotility is common, and often hinders the introduction of effective
      enteral nutrition. Small bowel motility problems are uncommon in the intensive
      care patient, and direct instillation of nutrients into the jejunum will allow
      enteral nutrition to begin without delay. However compared with gastric tubes,
      jejunal tubes are often difficult to insert, often requiring endoscopic or
      surgical techniques. The cause of gastric dysmotility is multifactorial.
      Treatment of underlying sepsis, pain, hypotension, dehydration and hyperglycaemia
      should occur, and opiates and dopamine should be avoided before commencing
      prokinetic agents. The patient's head should remain elevated, and oral or
      nasogastric cisapride (10 mg 6-hourly) administered. If this is not effective
      then erythromycin (e.g. 250 mg i.v. 8-hourly) may be included. CONCLUSIONS:
      Gastric dysmotility is common in the critically ill patient. However, treatment
      of the underlying conditions leading to gastroparesis and the introduction of
      prokinetic agents will allow the majority of patients to be successfully fed
      enterally.

PMID- 16599862
TI  - Osmolar disorders.
AB  - OBJECTIVE: To present a practical approach to the management of osmolar disorders
      by considering the mechanisms involved in their development. DATA SOURCES:
      Articles and published peer-review abstracts on the mechanisms and management of
      disorders of plasma osmolality. SUMMARY OF REVIEW: In health, plasma osmolality
      is determined largely by the concentration of sodium and its accompanying anion,
      and regulated by mechanisms that regulate body water. Water excess or deficiency
      causes hypo and hyper osmolality, respectively. Hyperosmolality may also be
      caused by an excess of body solutes, with the biochemical and clinical features
      depending on whether these compounds are impermeant (i.e. remain in the
      extracellular fluid) or permeant (i.e. are distributed throughout the total body
      water). Sodium metabolism is regulated by those mechanisms that regulate
      extracellular fluid volume. An increase (or decrease) in total body sodium is
      associated with retention (or excretion) of body water, an increase (or decrease)
      in the extracellular fluid (ECF) volume, and no change in plasma osmolality. The
      initial presentation of an osmolar disorder is usually with an abnormal plasma
      sodium, therefore management often focuses on treatment of hypo or
      hypernatraemia. However, treatment requires an estimation of all fluid and solute
      excesses and deficiencies, with the need or otherWise for prompt correction
      depending upon the nature of the disorder and time taken for it to develop.
      CONCLUSIONS: Osmolar disorders are associated with varying changes in total body
      fluid and solute. Consideration of these changes, using a body fluid compartment
      model, is useful in understanding the abnormalities present and to facilitate
      management.

PMID- 16599863
TI  - An appraisal of the impact of management guidelines in traumatic brain injury.
AB  - OBJECTIVE: To consider the evidence for the beneficial effects of the current
      management guidelines in traumatic brain injury, and to highlight the important
      issues. DATA SOURCES: Articles and published peer-review abstracts about the
      mechanisms and management of traumatic brain injury. SUMMARY OF REVIEW:
      Guidelines for the management of traumatic brain injury focus on the recognition,
      detection and prevention of secondary brain insults. Defence of cerebral
      perfusion pressure with optimisation of cerebral blood flow and substrate
      delivery, form the vanguard of these guidelines. The impact of guidelines per se
      on outcome is difficult to determine due to rapid changes in practice and a
      dearth of controlled evidence predating these guidelines. Technological
      developments in multimodal monitoring may identify trends in changing practice.
      However, there are still significant limitations in the accuracy of assessment of
      the underlying neuropathological processes. The impact of management strategies
      using current or novel therapies on these neuropathological processes is
      difficult to assess in randomised controlled trials due to small sample sizes and
      heterogeneous practice. Preliminary studies using continuous multimodal
      monitoring in accordance with current management guidelines have identified that
      episodes of sustained jugular venous desaturation were significantly reduced,
      indicating that potentially harmful episodes of cerebral oligaemia were
      prevented. Although the impact of these strategies on outcome was favourable,
      limitations in these studies do not allow firm outcome based assessments.
      However, these studies suggest that by defending cerebral perfusion pressure,
      potentially ischaemic or hypoxic cerebral insults may be prevented and may result
      in a reassessment of the indications and clinical utility of neuromonitoring.
      CONCLUSIONS: The impact of management guidelines in traumatic brain injury on
      patient outcome has been difficult to determine. However, there is a large body
      of uncontrolled evidence that suggests secondary global cerebral ischaemia
      hypoxic insults are the major determinants in influencing outcome and that
      therapeutic interventions that maintain and defend cerebral perfusion pressures
      may improve outcome.

PMID- 16599864
TI  - Group A streptococcal fasciitis.
AB  - OBJECTIVE: To review the current understanding of group A streptococcal
      fasciitis; the different bacterial serotypes, the role of superantigens,
      antibiotic and other therapies, and transmission to house hold contacts and
      health care workers. DATA SOURCES: Articles and published abstracts on the
      mechanisms and management of group A streptococcal fasciitis. SUMMARY OF REVIEW:
      The development of streptococcal fasciitis depends on the inoculation of a
      susceptible individual (i.e. one who has not been previously exposed to that
      particular serotype or superantigen) with a virulent streptococcus that has the
      ability to produce superantigens. The superantigens produce an excessive
      stimulation of the immune system, with a subsequent outpouring of inflammatory
      cytokines causing the multiorgan failure that characterises both streptococcal
      necrotising fasciitis as well as streptococcal toxic shock syndrome. Effective
      management of streptococcal necrotising fasciitis requires an early diagnosis,
      appropriate surgery, administration of clindamycin (600 mg/70 kg i.v. 6-hourly),
      penicillin G (1.2 g/70 kg i.v. 2 to 4-hourly), and polyvalent immunoglobulin (0.2
      - 0.4 g/kg/day i.v. for 3 - 5 days). Household and health workers in close
      contact with the patient need to be warned to present to medical care early if
      they develop any signs of an infection. CONCLUSIONS: Necrotising fasciitis is a
      severe disorder which is commonly caused by group A streptococcus. Early
      diagnosis and effective management with surgery, antibiotics and polyvalent
      immunoglobulin will reduce mortality. Further studies concerning the risk of
      transmission of the organism to close contacts need to be performed.

PMID- 16599865
TI  - Acute pernicious (sho-shin) beri-beri: a report of three cases.
AB  - Acute pernicious or sho-shin beri-beri is characterised by haemodynamic and
      biochemical features which include hypotension, high cardiac output, low
      peripheral vascular resistance, lactic acidosis and high mixed venous content.
      The disorder is a metabolic emergency and requires immediate treatment with
      intravenous thiamine. Three cases are described which were successfully treated
      with intravenous thiamine (500 mg intravenously, followed by 100 mg 8-hourly for
      24 hours then 100 mg daily) without using catecholamines or sodium bicarbonate.
      Digoxin was used in two cases to manage cardiac dysfunction which was poorly
      responsive to thiamine.

PMID- 16599866
TI  - A simple bedside approach to measurement of respiratory mechanics in critically
      ill patients.
AB  - OBJECTIVE: To describe and evaluate clinically applicable approaches to
      measurement of respiratory mechanics in critically ill patients. DATA SOURCES:
      Methodological and evaluation studies of respiratory mechanics in critically ill
      patients from relevant MEDLINE searches. SUMMARY OF REVIEW: In ventilated
      subjects clinically important respiratory system mechanics can be measured using
      airway pressure and flow data. However, since the respiratory system consists of
      the lung and chest wall, and chest wall mechanics can markedly alter respiratory
      system mechanics, it is preferable to compartmentalise these parameters with
      concurrent measurement of oesophageal, and preferably gastric pressure.
      Additional care must be taken with interpretation of these data since elastance
      and resistance may be influenced by frequency, volume, volume history and flow.
      Tissue viscoelasticity and non-homogeneity of regional time constants are
      responsible for stress adaptation, which can be measured simply, and accounts for
      some of these effects on elastance and resistance, and for a systematic
      difference between static and dynamic intrinsic PEEP. Elastance can be measured
      using the end-inspiratory occlusion technique, or from either static or dynamic
      volume-pressure curves. PEEP-mediated recruitment can be measured following
      referencing of these curves to FRC. Similarly, resistance can be measured from
      either end-inspiratory occlusion or dynamic pressure and flow data. CONCLUSIONS:
      Some of this information is available on modern ventilators, but greater insight
      requires measurement and manipulation of flow and pressure data using a
      pneumotachograph and pressure transducers. Given the importance of respiratory
      mechanics in the management of many critically ill patients, and given how poorly
      the respiratory system is monitored compared with the cardiovascular system, it
      is worth considering making this simple but additional effort.

PMID- 16599867
TI  - Recent advances in paediatric ventilation.
AB  - BACKGROUND: To review the recent advances in ventilatory therapy for acute
      respiratory failure in children. DATA SOURCES: Recent published peer-review
      articles on mechanical ventilation for acute respiratory failure in children.
      SUMMARY OF REVIEW: Advances in conventional treatment for acute respiratory
      failure (e.g. mechanical ventilation) have not increased survival in children.
      However, recent therapies including high frequency ventilation, extracorporeal
      membrane oxygenation, nitric oxide and liquid ventilation have reported improved
      outcomes. The rationale and use of each are presented. CONCLUSIONS: High
      frequency ventilation exists in three forms, although only high frequency
      oscillation appears to show any benefit in the management of acute respiratory
      failure refractory to conventional mechanical ventilation. Extracorporeal
      oxygenation has halved mortality in neonates with acute respiratory failure, and
      has been used successfully in non-neonate patients. Inhaled nitric oxide from 6
      to 20 parts per million improves oxygenation in paediatric patients with acute
      respiratory failure and congenital heart disease (particularly in the presence of
      pulmonary arterial hypertension). Liquid ventilation or perfluorocarbon
      associated gas exchange has also been used to treat acute respiratory failure in
      paediatric patients, with partial liquid ventilation particularly appearing to
      show promise.

PMID- 16599868
TI  - The oxyhaemoglobin dissociation curve in critical illness.
AB  - OBJECTIVE: To review the status of haemoglobin-oxygen affinity in critical
      illness and investigate the potential to improve gas exchange, tissue oxygenation
      and outcome by manipulations of the oxyhaemoglobin dissociation curve. DATA
      SOURCES: Articles and published peer-review abstracts. SUMMARY OF REVIEW: The P50
      of a species is determined by natural selection according to animal size, tissue
      metabolic requirements and ambient oxygen tension. In right to left shunting
      mathematical modeling indicates that an increased P50 defends capillary
      oxygenation, the one exception being sustained hypercapnia. Increasing the P50
      should also be protective in tissue ischaemia, and this is supported by modeling
      and experimental evidence. Most studies of critically ill patients have indicated
      reduced 2,3-DPG concentrations. This is probably due to acidaemia, and the in
      vivo P50 is likely to be normal despite low 2,3-DPG levels. It may soon be
      possible to achieve significant P50 elevations without potentially harmful
      manipulations of acid-base balance or hazardous drug therapy. CONCLUSIONS:
      Despite encouraging theoretical and experimental data, it is not known whether
      manipulations of the P50 in critical illness can improve gas exchange and tissue
      oxygenation or improve outcome. The status of the P50 may warrant more routine
      quantification and consideration along with the traditional determinants of
      tissue oxygen availability.

PMID- 16599869
TI  - Percutaneous tracheostomy.
AB  - OBJECTIVE: To review the indications and complications of the percutaneous
      tracheostomy compared with the standard surgical tracheostomy in the critically
      ill patient. DATA SOURCES: A review of studies reported from 1966 to 1998 and
      identified through a MEDLINE search on percutaneous tracheostomy. SUMMARY OF
      REVIEW: A tracheostomy is often performed in the critically ill patient when
      airway access, airway protection and mechanical ventilation are required for a
      prolonged period. The percutaneous dilatational technique rather than the
      standard surgical technique is now often used as it can be easily and rapidly
      performed at the bedside. The two percutaneous tracheostomy procedures most often
      used are the progressive dilatational and the guide wire dilational forceps
      techniques. The complications associated with both methods include misplacement
      of the insertion needle, Seldinger wire or dilator, insertion failure, fracture
      of the tracheal ring, bleeding, barotrauma, bacteraemia and death. The incidence
      of these complications often depends on the experience of the operator and while
      bronchoscopic guidance has been used to reduce the number of complications, it
      prolongs the procedure, requires a separate operator and may cause hypercapnoea.
      CONCLUSIONS: In the critically ill patient who requires a tracheostomy, the
      percutaneous rather than the standard surgical technique is the method of choice
      as it can be performed at the bedside, leaves a smaller scar after decannulation
      and may be associated with fewer complications compared with the standard
      surgical technique.

PMID- 16599870
TI  - Albumin and resuscitation: a sense of Deja Vu.

PMID- 16599871
TI  - Freedom of expression and editorial freedom - an open letter.

PMID- 16599872
TI  - "If you don't look for Canaries you won't find them".

PMID- 16599873
TI  - Recruiting without over-stretching.

PMID- 16599874
TI  - Hyperbaric oxygen therapy: time for a change.

PMID- 16599875
TI  - Oxygenation is not improved by partial liquid high frequency ventilation using a
      high lung volume strategy. An experimental study.
AB  - OBJECTIVE: To investigate the effect on oxygenation and lung damage of partial
      perfluorocarbon liquid high frequency oscillatory ventilation (PL-HFOV) versus
      high frequency oscillatory ventilation (HFOV) alone, in rabbits with acute lung
      injury, using high lung volume strategy HFOV. METHODS: Twelve adult New Zealand
      white rabbits were initially ventilated with HFOV after anaesthesia, sedation and
      paralysis. After induction of lung injury with saline lavage, all animals
      received a single sigh breath of 30 cmH(2)O for 30 seconds. They were then
      allocated to receive either HFOV alone (n = 6) or PL-HFOV (n = 6). Arterial blood
      gases were taken pre- and post-lavage and then hourly for 5 hours. The
      oxygenation index (OI, in cmH(2)O/mmHg) was calculated using the formula: OI =
      (MAP x F(I)O(2) x 100) / PaO(2). The lungs were then removed for histological
      examination to score lung injury. RESULTS: Two rabbits died in the PL-HFOV group
      and none in the HFOV group, p = 0.45 (Fisher's exact test). At one hour the
      oxygenation index (OI) was 4.5 in the HFOV group and 6.6 in the PL-HFOV group, p
      = 0.49 and the PaO(2) was 374 mmHg in the HFOV group and 311 mmHg in the PL-HFOV
      group, p = 0.39. Average OI over the first three hours was 3.6 in the HFOV group
      and 5.0 in the PL-HFOV group, p = 0.27 and the PaO(2) was 404 mmHg in the HFOV
      group and 337 mmHg in the PL-HFOV group, p = 0.12. The lung histology damage
      score was 2.33 in the HFOV group and 2.50 in the PL-HFOV group, p = 0.83.
      CONCLUSIONS: In this model of acute lung injury, using a high volume HFOV
      strategy to optimise lung recruitment, PL-HFOV did not result in any further
      improvement in oxygenation when compared with HFOV alone. The question of safety
      with PL-HFOV remains.

PMID- 16599876
TI  - Management of status epilepticus.
AB  - OBJECTIVE: To review the aetiology and treatment of status epilepticus and
      present a practical approach to its management. DATA SOURCES: A review of studies
      reported from 1966 to 1998 and identified through a MEDLINE search of the English
      language literature on metabolic and toxic seizures and status epilepticus.
      SUMMARY OF REVIEW: Status epilepticus describes a condition of prolonged or
      repetitive seizures and is refractory if it lasts longer than 20-30 minutes
      despite therapy. It may cause primary cerebral injury due to prolonged
      uncontrolled neuronal discharge or secondary cerebral injury due to hypoxia and
      hypothermia. To minimise neural damage, resuscitation, correction of metabolic
      defects and termination of the seizures should be achieved rapidly (i.e. within
      10 minutes). Initial treatment includes intravenous lorazepam (2-8 mg/70kg) or
      diazepam (5-20 mg/70kg) and phenytoin (1500 - 2000 mg/70 kg) which will control
      seizures in up to 70% of patients. If status epilepticus becomes resistant to the
      initial treatment, the patient should be managed in a monitored environment, as
      further therapy usually includes agents that may anaesthetise the patient. In an
      adult patient, 'second-line' drugs include intravenous phenobarbitone (100 -1000
      mg), magnesium sulphate (10 - 15 mmol), midazolam (8-20 mg followed by an
      infusion at 4-30 mg/hour), propofol (50 - 150 mg followed by an infusion at 100 
      500 mg/hour), thiopentone (200 - 500 mg followed by an infusion at 100 - 500
      mg/hr), lignocaine (100 -150 mg followed by an infusion of 150-200 mg/h),
      ketamine (50 - 100 mg followed by 50 - 100 mg/h), or isoflurane (0.5 - 1.5%),
      added singly or in combination. If the patient requires paralysis to reduce the
      metabolic effects of a prolonged seizure then continuous electroencephalography
      is required. CONCLUSIONS: Status epilepticus is a medical emergency requiring
      urgent termination of seizures and management of the initiating factors.
      Lorazepam or diazepam and phenytoin are recommended as 'first-line' therapy.

PMID- 16599877
TI  - Hyperlactaemia without acidosis - an investigation using an in vitro model.
AB  - OBJECTIVE: To use an in vitro dilutional blood model to simulate aerobic
      hyperlactaemia, and to question whether base excess and anion gap distinguish
      aerobic from anaerobic lactate production. METHODS: Cooled fresh blood was
      diluted (3:1) with nine different crystalloid solutions, each with a sodium
      concentration of 140 mmol/L but with strong ion difference values ranging from -5
      mEq/L to 40 mEq/L due to varying concentrations of Cl(-), HCO(3)(-) and lactate
      anions. Normocapnic pH and base excess values post-dilution were determined by
      gas equilibration. Strong ion difference and anion gap values were measured.
      RESULTS: There was close correlation between the normocapnic pH and both the
      diluent strong ion difference and the final strong ion difference of the diluted
      specimens (R(2) = 0.96 and 0.89 respectively). This was independent of lactate
      concentrations in diluent or in post-dilution plasma. Where lactate-containing
      crystalloid was added, base excess, normocapnic pH and anion gap were strongly
      correlated with the final plasma lactate concentrations (R(2) >or= 0.99).
      However, only at final lactate concentrations of approximately 10 - 15 mmol/L did
      values of base excess, normocapnic pH or anion gap indicate metabolic acidosis.
      CONCLUSIONS: Hyperlactaemia from any source reduces strong ion difference and
      base excess and increases the anion gap, but values may remain in the normal
      range until hyperlactaemia is severe. Abnormal base excess and anion gap values
      do not distinguish aerobic from anaerobic lactate production. Normal values
      merely reflect low sensitivity to small lactate elevations (aerobic or
      otherwise).

PMID- 16599878
TI  - Brown snake envenomation complicating near drowning and amphetamine overdose.
AB  - A case is described of a near drowning and amphetamine overdose in a patient who
      developed rapidly progressive coagulopathy, thrombocytopaenia and anuria. As the
      coagulation abnormality was not perceived to be in keeping with the amphetamine
      toxicity, a septic and toxological screen were performed which revealed a
      positive urine result for Pseudonaja texilis envenomation. Despite resuscitation
      using coagulation factors and monovalent antivenom, the patient died. This case
      highlights the importance of early testing for envenomation when an atypical
      coagulopathy is present.

PMID- 16599879
TI  - An unusual cause for cardiac arrest.
AB  - We report a case of organophosphate poisoning presenting as a cardiac arrest. The
      diagnosis was delayed due to the absence of a history of insecticide ingestion
      and the unusually acute presentation. Cardiac arrest with bradycardia poorly
      responsive to adrenaline and responsive to high dose atropine should alert the
      clinician to the possibility of an anticholinesterase poisoning. Early diagnosis
      is essential in order to manage these patients appropriately and increase the
      probability of survival.

PMID- 16599880
TI  - Severe acute necrotising pancreatitis caused by sodium valproate: a case report.
AB  - Drug induced acute pancreatitis is an uncommon cause for acute pancreatitis. To
      make this diagnosis confidently, certain criteria should be fulfilled. The
      patient should be receiving the drug when acute pancreatitis develops and the
      pancreatitis should resolve with cessation of the drug. Also, other causes need
      to be excluded, and while the patient should ideally have recurrence of the
      pancreatitis if the drug is recommenced, as a confirmatory test this is not
      usually performed. A case is reported of severe acute necrotising pancreatitis
      associated with the use of sodium valproate. Sixteen years previously a similar
      but milder episode of possible acute pancreatitis occurred in this patient,
      resulting in cessation of sodium valproate. On the present occasion the patient
      required aggressive resuscitation, inotropic and ventilatory support, antibiotics
      and enteral feeding for a prolonged period before making a complete recovery.

PMID- 16599881
TI  - MDMA toxicity presenting with severe hyperpyrexia: a case report.
AB  - Ingestion of even small amounts of MDMA ('ecstasy') by a small subset of the
      population may result in a potentially fatal clinical syndrome of severe
      hyperpyrexia, cardiovascular collapse, coagulopathy, rhabdomyolysis and multiple
      organ failure. Rapid and aggressive temperature control is of utmost importance
      in the management of these patients. We report a case of MDMA toxicity presenting
      with severe hyperpyrexia (43 degrees C) who survived after a rapid reduction in
      temperature to 36 degrees C within 60 minutes following active surface cooling,
      cooled (approximately 4 degrees C) intravenous solutions, urinary and gastric
      lavage solutions and replacement fluids for continuous veno-venous diafiltration.

PMID- 16599882
TI  - Acute asthma and the life threatening episode.
AB  - OBJECTIVE: To present a clinical approach to the management of acute asthma and
      the life threatening episode of asthma. DATA SOURCES: A review of published peer
      review articles and studies reported from 1966 to 1999 and identified through a
      MEDLINE search on the management of acute asthma, status asthmaticus and acute
      fulminant asthma. SUMMARY OF REVIEW: Asthma is a disease caused by a chronic
      desquamative eosinophilic bronchitis with airway hyper-responsiveness to specific
      and non-specific stimuli. It is characterised clinically by episodic airflow
      obstruction. A life threatening episode indicates the presence of one of the
      three clinical types; acute severe asthma (an acute episode of bronchospasm where
      the FEV(1) is 30% or less than the predicted value), status asthmaticus (where
      the episode becomes resistant to beta-adrenergic agonists and corticosteroids),
      or acute fulminant asthma (where the onset is rapid and severe and the patient is
      obtunded). Management of acute severe asthma includes oxygen, continuous
      nebulised salbutamol (until an adequate clinical response occurs) and intravenous
      hydrocortisone (200 mg/70 kg i.v. followed by 50 mg/70 kg hourly or 200 mg 4
      hourly). The patient's speech, conscious state, pulse and respiratory rate, peak
      expiratory flow rate, oximetry and blood gases should be monitored, and if there
      is no improvement or the patient deteriorates, admission to an intensive care
      unit is required. Additional therapy includes intravenous aminophylline (2mg/kg,
      followed by 4 mg/kg over 30 minutes), nebulised ipratropium (500 microg 6
      hourly), high dose inhaled corticosteroids, intravenous magnesium sulphate (5-10
      mmol as a bolus with 40 mmol over 1-2 hours), and even inhaled helium oxygen
      mixtures. With further deterioration or for the management of acute fulminant
      asthma, intravenous adrenaline (20-200microg bolus followed by an infusion of 1
      10 microg/min) is often used. Endotracheal intubation, with mechanical
      ventilation (using low tidal volumes and low respiratory rates) ketamine
      anaesthesia (1-2 mg/kg followed by 50 microg/kg/min), inhaled anaesthetic agents
      (e.g. diethyl ether) and even extracoporeal life support (using extracorporeal
      membrane oxygenation) may be required. CONCLUSIONS: Inhaled salbutamol and
      intravenous corticosteroids are initially administered to manage the episode of
      acute severe asthma. Management of acute fulminant asthma or status asthmaticus
      requires admission to the intensive care unit and may require anaesthetic agents
      and complex life support techniques.

PMID- 16599883
TI  - Cardiovascular effects of mechanical ventilation.
AB  - OBJECTIVE: To review the cardiovascular effects of spontaneous breathing and
      mechanical ventilation in healthy and pathological states. DATA SOURCES: A review
      of articles published in peer-reviewed journals from 1966 to 1998 and identified
      through a MEDLINE search on cardiopulmonary interaction. SUMMARY OF REVIEW:
      Respiration has a hydraulic influence upon cardiovascular function. Pulmonary and
      cardiac pathology alter this interaction. Spontaneous inspiration increases right
      ventricular (RV) preload and left ventricular (LV) afterload. Mechanical
      ventilation with positive pressure (MV) reduces LV preload and afterload. The
      influence of MV upon the cardiovascular system (CVS), particularly in critically
      ill patients, depends upon the mode of ventilation and the pre-existing cardiac
      and respiratory status. The influence of these factors is reviewed. Consideration
      of these parameters will enable the clinician to predict the likely effect of MV
      and develop strategies to minimise adverse events. CONCLUSIONS: Mechanical
      ventilation has an adverse effect upon the CVS in healthy subjects and in
      patients with pulmonary pathology, particularly in the presence of preload
      dependent LV dysfunction or afterload-induced RV dysfunction. Mechanical
      ventilation may benefit cardiac function in patients with respiratory failure and
      afterload-dependent or exercise-induced LV dysfunction.

PMID- 16599884
TI  - Let's leave behind dogma!

PMID- 16599885
TI  - Naked in the electronic age.

PMID- 16599886
TI  - Echocardiography in the critically ill.

PMID- 16599888
TI  - Difficulty with the Ciaglia Blue Rhino dilator.

PMID- 16599887
TI  - Acid-base and strong ion difference.

PMID- 16599889
TI  - Recent advances in cardiopulmonary resuscitation (CPR).

PMID- 16599890
TI  - Hyponatraemia and speed of correction. Why is there a dilemma?

PMID- 16599891
TI  - Preoperative cardiopulmonary risk assessment--more science and less art.

PMID- 16599892
TI  - Lung oxygen consumption and its measurement.

PMID- 16599893
TI  - With faltering steps still we come.

PMID- 16599894
TI  - Oxygen consumption and lactate release by the lung after cardiopulmonary bypass
      and during septic shock.
AB  - OBJECTIVE: We sought to determine whether a correlation exists between lung
      lactate release and lung oxygen consumption by studying adult intensive care
      patients, either after cardiopulmonary bypass (CPB) or with septic shock.
      METHODS: A prospective observational study of six post cardiopulmonary bypass
      patients and seven patients with septic shock was performed in an intensive care
      unit of a major teaching hospital. Pulmonary oxygen consumption was estimated by
      subtracting oxygen consumption calculated using the reverse Fick equation (V
      O2Fick) from that measured by indirect calorimetry (V O2meas). Pulmonary lactate
      release was derived from the difference between arterial and mixed-venous
      lactate, multiplied by cardiac output. RESULTS: Pulmonary oxygen consumption
      comprised a substantial component of total oxygen consumption (CPB-median: 20.6%;
      interquartile range (IQR): 15.4 - 27.3%; septic shock-median: 32.3%; IQR: -4.0 -
      35.4%). Lung lactate release occurred both after CPB (median: 27.5 mmol/hr; IQR:
      24.8-64.1 mmol/hr) and with septic shock (median: 55.4 mmol/hr; IQR: 24.3 - 217.6
      mmol/hr). Although no correlation was found between lung lactate release and
      pulmonary oxygen consumption, lactate release correlated with V O2meas and V
      O2Fick in septic patients (p < 0.005). CONCLUSIONS: We conclude that lung oxygen
      consumption and lactate release are substantial in conditions associated with
      lung inflammation. Lactate release and lung oxygen consumption may not share a
      common pathogenesis, however there is an association between lung lactate release
      and systemic oxygen consumption in sepsis.

PMID- 16599895
TI  - The efficacy of cardiopulmonary resuscitation in the prone position.
AB  - OBJECTIVE: To ascertain whether cardiopulmonary resuscitation (CPR) is effective
      when performed on a mannequin in the prone position. METHODS: Thirty six
      registered nurses each performed 100 consecutive chest compressions on a Laerdal
      Resusci-Annie mannequin immediately after an annual update of CPR technique from
      an Advanced Life Support (ALS) instructor. Compressions were performed on a
      mannequin turned to the prone position, on a standard examination couch. A
      gel.filled pad was placed between the sternum and couch. Nurses were instructed
      once to perform compressions in the midline, two.thirds the way up the torso
      'between imaginary scapulae'. Efficacy of compressions was measured using an
      integral 'skillmeter' in the mannequin. RESULTS: Of 3600 chest compressions
      performed, 3376 were assessed by the skillmeter. 1168 (34.6%) compressions were
      4.5 cm in depth, 1370 (40.6%) were 2.4 cm in depth, and 868 (24.6%) were less
      than 2 cm. Sixty one percent of nurses were able to perform adequate CPR at some
      stage through the cycle. Forty one percent managed to perform adequate CPR
      throughout the cycle. CONCLUSIONS: Efficient CPR can be performed on a mannequin
      in the prone position, although additional instruction in technique is required.
      This may be applicable to patients turned to the prone position.

PMID- 16599896
TI  - Conservative management of a posterior tracheal tear: a case report.
AB  - We describe a case of posterior tracheal wall tear managed conservatively with a
      successful outcome. The presentation of a sudden increase in cuff volume and
      subcutaneous emphysema presents a challenging management problem requiring
      careful bronchoscopic and computed tomography delineation and isolation of the
      injury using a double lumen tube. This case also highlights the vulnerability of
      the trachea to injury from airway intervention and considers the possible
      mechanisms of tracheal injuries during the commonly performed intensive care
      procedure of percutaneous tracheostomy.

PMID- 16599897
TI  - Massive baclofen overdose.
AB  - A case is presented of a massive baclofen overdose with the highest blood
      baclofen concentrations currently reported. Interesting clinical features
      included profound hypotension, distributive shock and absent brainstem reflexes.
      Cerebral recovery was surprisingly slow but complete, and was then unexpectedly
      terminated by a sudden major splenic arterial haemorrhage followed by a severe
      haemorrhage of the aorta which proved to be due to cystic medial necrosis. This
      arterial anatomic abnormality and cause of death may have been coincidental, or
      may instead be a previously unreported complication of massive baclofen toxicity.

PMID- 16599898
TI  - Preoperative cardiopulmonary risk assessment by cardiopulmonary exercise testing.
AB  - OBJECTIVE: To review the strategies for identification and subsequent management
      of high-risk patients that have been proposed to reduce perioperative morbidity
      and mortality. DATA SOURCES: Articles and published reviews of studies on
      evaluation and management of patients to reduce perioperative morbidity and
      mortality. SUMMARY OF REVIEW: Many strategies have been devised to evaluate the
      perioperative risk in elderly patients, particularly those who are about to
      undergo major intra-abdominal surgery. An assessment of cardiac and pulmonary
      responses to exercise-induced stress (i.e. cardiopulmonary exercise testing)
      using a bicycle ergometer, metabolic cart (to measure oxygen uptake and carbon
      dioxide excretion) and a 12 lead electrocardiograph has been found to be a
      non.invasive test that is quick, cheap, easy to perform and requires no special
      preparation. It has advantages over any other preoperative test by defining
      operative risk and allowing logical triage according to objective risk
      assessment. It is able to objectively evaluate the extent of any cardiac failure
      (by assessing the anaerobic threshold), myocardial ischaemia, provides insight
      into stroke index, the presence of pulmonary artery hypertension and defines
      obstructive and restrictive lung disease and ventilation perfusion inequality
      better than conventional preoperative respiratory function tests. CONCLUSIONS: In
      patients who are about to undergo major intra-abdominal surgery, preoperative
      cardiopulmonary exercise testing is an excellent predictor of risk in the
      postoperative period. No other test is able to offer such a comprehensive
      preoperative risk evaluation for an operative patient.

PMID- 16599899
TI  - Acute haemorrhagic stroke.
AB  - OBJECTIVE: To review the management and some of the recent advances in acute
      haemorrhagic stroke. DATA SOURCES: Articles and published reviews on acute
      haemorrhagic stroke. SUMMARY OF REVIEW: Hypertensive intracerebral haemorrhage or
      subarachnoid haemorrhage (SAH) from a ruptured intracranial saccular aneurysm are
      the commonest causes for an acute haemorrhagic stroke. Both lesions are often
      clinically characterised by a sudden severe headache and vomiting with the
      remaining neurological features dependent on the site of the lesion. The
      diagnosis requires an urgent non-contrast cerebral computed tomography (CT) scan
      and a lumbar puncture if the CT scan fails to demonstrate intracranial blood.
      Treatment of both intracerebral haemorrhage and SAH includes resuscitation (e.g.
      cardiovascular and respiratory support) and preventative therapy (e.g.
      maintaining hydration and nutrition, and preventing aspiration and pressure
      sores, etc). Further management of an intracerebral haemorrhage by removing the
      clot is only beneficial if it is near the surface (although stereotactic catheter
      insertion and infusion of thrombolytics have been used with variable success with
      deeper haematomata) and if there are signs of intracerebral shift or compression
      of vital structures (e.g. cerebellar haematoma). Management of SAH still requires
      nimodipine and early angiography with surgery to reduce the incidence of cerebral
      vasospasm and rebleeding, respectively. While intravascular techniques using the
      Guglielmi detachable coil have improved the outcome in surgically inaccessible
      (and accessible) aneurysms, management of resistant cerebral vasospasm using
      'triple H' therapy (i.e. hypertension, hypervolaemia and haemodilution),
      intraarterial papaverine, angioplasty, and intrathecal tPA, have not been
      uniformly successful. CONCLUSIONS: Acute haemorrhagic stroke requires an urgent
      non-contrast cerebral CT scan for diagnosis. Treatment of an intracerebral
      haematoma requires evacuation of the clot if accessible and if it is causing an
      intracerebral shift or compression of vital structures. Nimodipine and urgent
      surgery to reduce the incidence of cerebral vasospasm and rebleeding,
      respectively, are standard for the management of a patient with a SAH. While
      recent advances in intravascular techniques using the Guglielmi detachable coil
      hold promise, successful management of resistant cerebral vasospasm remains
      elusive.

PMID- 16599900
TI  - Safety and quality in intensive care.

PMID- 16599901
TI  - FFICANZCA's, it's time to vote with your subscriptions.

PMID- 16599902
TI  - A 24 year old woman admitted to the critical care unit, with 'resistant' asthma
      and a metabolic acidosis.

PMID- 16599903
TI  - Pulmonary artery catheters. Use them--but with due care.

PMID- 16599904
TI  - Interaction between Tiam1 and the Arp2/3 complex links activation of Rac to actin
      polymerization.
AB  - The Rac-specific GEF (guanine-nucleotide exchange factor) Tiam1 (T-lymphoma
      invasion and metastasis 1) regulates migration, cell-matrix and cell-cell
      adhesion by modulating the actin cytoskeleton through the GTPase, Rac1. Using
      yeast two-hybrid screening and biochemical assays, we found that Tiam1 interacts
      with the p21-Arc [Arp (actin-related protein) complex] subunit of the Arp2/3
      complex. Association occurred through the N-terminal pleckstrin homology domain
      and the adjacent coiled-coil region of Tiam1. As a result, Tiam1 co-localizes
      with the Arp2/3 complex at sites of actin polymerization, such as epithelial cell
      cell contacts and membrane ruffles. Deletion of the p21-Arc-binding domain in
      Tiam1 impairs its subcellular localization and capacity to activate Rac1,
      suggesting that binding to the Arp2/3 complex is important for the function of
      Tiam1. Indeed, blocking Arp2/3 activation with a WASP (Wiskott-Aldrich syndrome
      protein) inhibitor leads to subcellular relocalization of Tiam1 and decreased Rac
      activation. Conversely, functionally active Tiam1, but not a GEF-deficient
      mutant, promotes activation of the Arp2/3 complex and its association with
      cytoskeletal components, indicating that Tiam1 and Arp2/3 are mutually dependent
      for their correct localization and signalling. Our data suggests a model in which
      the Arp2/3 complex acts as a scaffold to localize Tiam1, and thereby Rac
      activity, which are both required for activation of the Arp2/3 complex and
      further Arp2/3 recruitment. This 'self-amplifying' signalling module involving
      Tiam1, Rac and the Arp2/3 complex could thus drive actin polymerization at
      specific sites in cells that are required for dynamic morphological changes.

PMID- 16599906
TI  - Implications of the difference between true and predicted breeding values for the
      study of natural selection and micro-evolution.
AB  - The ability to predict individual breeding values in natural populations with
      known pedigrees has provided a powerful tool to separate phenotypic values into
      their genetic and environmental components in a nonexperimental setting. This has
      allowed sophisticated analyses of selection, as well as powerful tests of
      evolutionary change and differentiation. To date, there has, however, been no
      evaluation of the reliability or potential limitations of the approach. In this
      article, I address these gaps. In particular, I emphasize the differences between
      true and predicted breeding values (PBVs), which as yet have largely been
      ignored. These differences do, however, have important implications for the
      interpretation of, firstly, the relationship between PBVs and fitness, and
      secondly, patterns in PBVs over time. I subsequently present guidelines I believe
      to be essential in the formulation of the questions addressed in studies using
      PBVs, and I discuss possibilities for future research.

PMID- 16599905
TI  - Disruption of inositol biosynthesis through targeted mutagenesis in Dictyostelium
      discoideum: generation and characterization of inositol-auxotrophic mutants.
AB  - myo-Inositol and its downstream metabolites participate in diverse physiological
      processes. Nevertheless, considering their variety, it is likely that additional
      roles are yet to be uncovered. Biosynthesis of myo-inositol takes place via an
      evolutionarily conserved metabolic pathway and is strictly dependent on inositol
      3-phosphate synthase (EC 5.5.1.4). Genetic manipulation of this enzyme will
      disrupt the cellular inositol supply. Two methods, based on gene deletion and
      antisense strategy, were used to generate mutants of the cellular slime mould
      Dictyostelium discoideum. These mutants are inositol-auxotrophic and show
      phenotypic changes under inositol starvation. One remarkable attribute is their
      inability to live by phagocytosis of bacteria, which is the exclusive nutrient
      source in their natural environment. Cultivated on fluid medium, the mutants lose
      their viability when deprived of inositol for longer than 24 h. Here, we report a
      study of the alterations in the first 24 h in cellular inositol, inositol
      phosphate and phosphoinositide concentrations, whereby a rapidly accumulating
      phosphorylated compound was detected. After its identification as 2,3-BPG (2,3
      bisphosphoglycerate), evidence could be found that the internal disturbances of
      inositol homoeostasis trigger the accumulation. In a first attempt to
      characterize this as a physiologically relevant response, the efficient in vitro
      inhibition of a D. discoideum inositol-polyphosphate 5-phosphatase (EC 3.1.3.56)
      by 2,3-BPG is presented.

PMID- 16599907
TI  - Modulation of sexual signalling by immune challenged male mealworm beetles
      (Tenebrio molitor, L.): evidence for terminal investment and dishonesty.
AB  - Organisms partition resources into life-history traits in order to maximise
      fitness over their expected lifespan. For the males of many species fitness is
      determined by qualitative and quantitative aspects of costly sexual signals: The
      notion that epigamic traits are costly forms the cornerstone of those theories
      that propose parasites drive sexual selection. Consequently studies examining
      this notion assume sexual signalling is honest (i.e. driven by cost) when they
      seek to identify correlations or causal links between male immune function and
      attractiveness. We demonstrate that immune challenged males of the mealworm
      beetle, Tenebrio molitor, increased their investment in epigamic pheromone
      signals: these males became significantly more attractive to females whilst
      increasing the activity of a key immune effector system. In other words males
      increase terminal reproductive effort (invest in attractiveness) in response to a
      survival threat (immune insult). Consequently the signal preferred by the female
      is dishonest when considering the male's condition.

PMID- 16599908
TI  - An indirect approach to imply trade-off shapes: population level patterns in
      resistance suggest a decreasingly costly resistance mechanism in a model insect
      system.
AB  - Trade-offs between life history and other traits play a key role in shaping the
      evolution of individuals. It is well established theoretically that the shapes of
      trade-off curves are as crucial to the evolutionary outcome as their strengths.
      However, measuring the shape of these relationships directly is often
      impractical. Here we use an indirect approach that examines the patterns seen
      within a population and then use theory to infer the shape of the trade-off
      curve. Using a bioassay we found that most individuals had either high
      susceptibility or relatively high resistance to a microparasite in a lepidopteran
      host population. According to general theory, this type of pattern in resistance
      would be most likely with a deceleratingly costly impact on fitness of increasing
      resistance. The implications and generality of the approach are discussed, along
      with the implications of the results to our understanding of the nature of innate
      resistance to parasites.

PMID- 16599909
TI  - Predicting the pathway to wind pollination: heritabilities and genetic
      correlations of inflorescence traits associated with wind pollination in Schiedea
      salicaria (Caryophyllaceae).
AB  - The transition from biotic to abiotic pollination was investigated using
      Schiedea, a genus exhibiting a remarkable diversity of inflorescence architecture
      associated with pollination biology. Heritabilities and genetic correlations of
      inflorescence traits were estimated in gynodioecious Schiedea salicaria
      (Caryophyllaceae), a species that has likely undergone a recent transition to
      wind-pollination. Using a partial diallel crossing design, significant narrow
      sense heritabilities were detected for inflorescence condensation (h2 = 0.56 to
      0.68 in the two sexes) and other traits related to the extent of wind pollination
      in Schiedea species. Heritabilities were generally higher in hermaphrodites than
      in females. Strong genetic correlations may constrain the evolution of some
      inflorescence traits that facilitate wind pollination, such as simultaneous
      shortening of inflorescence length and elongation of the subtending internode.
      The presence of significant narrow-sense heritabilities for traits associated
      with wind pollination suggests, however, that selection for more effective wind
      pollination in the windy, pollinator-limited environments where S. salicaria
      grows could lead to the evolution of the highly condensed inflorescences
      characteristic of other wind-pollinated species of Schiedea.

PMID- 16599910
TI  - Heritability of corticosterone response and changes in life history traits during
      selection in the zebra finch.
AB  - Vertebrates respond to environmental stressors through the neuro-endocrine stress
      response, which involves the production of glucocorticoids. We have selected
      independent, duplicate divergent lines of zebra finches for high, low and control
      corticosterone responses to a mild stressor. This experiment has shown that over
      the first four generations, the high lines have demonstrated a significant
      realized heritability of about 20%. However, the low lines have apparently not
      changed significantly from controls. This asymmetry in response is potentially
      because of the fact that all birds appear to be showing increased adaptation to
      the environment in which they are housed, with significant declines in
      corticosterone response in control lines as well as low lines. Despite the
      existence of two- to threefold difference in mean corticosterone titre between
      high and low lines, there were no observed differences in testosterone titre in
      adult male birds from the different groups. In addition, there were no
      consistent, significant differences between the lines in any of the life history
      variables measured--number of eggs laid per clutch, number of clutches or broods
      produced per pair, number of fledglings produced per breeding attempt, nor in any
      of egg, nestling and fledgling mortality. These results highlight the fact that
      the mechanisms that underlie variation in the avian physiological system can be
      modified to respond to differences between environments through selection. This
      adds an additional level of flexibility to the avian physiological system, which
      will allow it to respond to environmental circumstances.

PMID- 16599911
TI  - Genetic robustness and selection at the protein level for synonymous codons.
AB  - Synonymous codons are neutral at the protein level, therefore natural selection
      at the protein level should have no effect on their frequencies. Synonymous
      codons, however, differ in their capacity to reduce the effects of errors: after
      mutation, certain codons keep on coding for the same amino acid or for amino
      acids with similar properties, while other synonymous codons produce very
      different amino acids. Therefore, the impact of errors on a coding sequence
      (genetic robustness) can be measured by analysing its codon usage. I analyse the
      codon usage of sequenced nuclear and cytoplasmic genomes and I show that there is
      an extensive variation in genetic robustness at the DNA sequence level, both
      among genomes and among genes of the same genome. I also show theoretically that
      robustness can be adaptive, that is natural selection may lead to a preference
      for codons that reduce the impact of errors. If selection occurs only among the
      mutants of a codon (e.g. among the progeny before the adult phase), however, the
      codons that are more sensitive to the effects of mutations may increase in
      frequency because they manage to get rid more easily of deleterious mutations. I
      also suggest other possible explanations for the evolution of genetic robustness
      at the codon level.

PMID- 16599913
TI  - Spatial heterogeneity and the stability of host-parasite coexistence.
AB  - Spatially heterogeneous environments can theoretically promote more stable
      coexistence of hosts and parasites by reducing the risk of parasite attack either
      through providing permanent spatial refuges or through providing ephemeral
      refuges by reducing dispersal. In experimental populations of Pseudomonas
      aeruginosa and the bacteriophage PP7, spatial heterogeneity promoted stable
      coexistence of host and parasite, while coexistence was significantly less stable
      in the homogeneous environment. Phage populations were found to be persisting on
      subpopulations of sensitive bacteria. Transferring populations to fresh
      microcosms every 24 h prevented the development of permanent spatial refuges.
      However, the lower dispersal rates in the heterogeneous environment were found to
      reduce parasite transmission thereby creating ephemeral refuges from phage
      attack. These results suggest that spatial heterogeneity can stabilize an
      otherwise unstable host-parasite interaction even in the absence of permanent
      spatial refuges.

PMID- 16599912
TI  - Cannabinoid receptors in invertebrates.
AB  - Two cannabinoid receptors, CB1 and CB2, are expressed in mammals, birds,
      reptiles, and fish. The presence of cannabinoid receptors in invertebrates has
      been controversial, due to conflicting evidence. We conducted a systematic review
      of the literature, using expanded search parameters. Evidence presented in the
      literature varied in validity, ranging from crude in vivo behavioural assays to
      robust in silico ortholog discovery. No research existed for several clades of
      invertebrates; we therefore tested for cannabinoid receptors in seven
      representative species, using tritiated ligand binding assays with [3H]CP55,940
      displaced by the CB1-selective antagonist SR141716A. Specific binding of
      [3H]CP55,940 was found in neural membranes of Ciona intestinalis (Deuterstoma, a
      positive control), Lumbricusterrestris (Lophotrochozoa), and three ecdysozoans:
      Peripatoides novae-zealandiae (Onychophora), Jasus edwardi (Crustacea) and
      Panagrellus redivivus (Nematoda); the potency of displacement by SR141716A was
      comparable to measurements on rat cerebellum. No specific binding was observed in
      Actinothoe albocincta (Cnidaria) or Tethya aurantium (Porifera). The phylogenetic
      distribution of cannabinoid receptors may address taxonomic questions; previous
      studies suggested that the loss of CB1 was a synapomorphy shared by ecdysozoans.
      Our discovery of cannabinoid receptors in some nematodes, onychophorans, and
      crustaceans does not contradict the Ecdysozoa hypothesis, but gives it no
      support. We hypothesize that cannabinoid receptors evolved in the last common
      ancestor of bilaterians, with secondary loss occurring in insects and other
      clades. Conflicting data regarding Cnidarians precludes hypotheses regarding the
      last common ancestor of eumetazoans. No cannabinoid receptors are expressed in
      sponges, which probably diverged before the origin of the eumetazoan ancestor.

PMID- 16599914
TI  - Do mothers producing large offspring have to sacrifice fecundity?
AB  - We artificially selected on egg size in a butterfly to study the consequences for
      fecundity, reproductive effort and offspring fitness. Correlated responses in
      either pupal mass, larval or pupal development time were virtually absent.
      Offspring size was positively related to fitness, but only partly traded off
      against fecundity. Rather, total reproductive effort (measured as fresh mass),
      egg water content and the decline of egg size with female age increased in the
      large-egg selected lines compared to either small-egg or control lines.
      Accounting for these effects showed that reproductive investment (in dry mass)
      was in fact similar across lines. Such mechanisms may enable increased investment
      in (early) offspring without a reduction in their number, revealing a much more
      complex picture than a simple trade-off between offspring size and number.
      Substantial variation among replicates suggests that there are different
      underlying mechanisms for change, rather than any single, unitary pathway.

PMID- 16599915
TI  - Ecological specialization correlates with genotypic differentiation in sympatric
      host-populations of the pea aphid.
AB  - The pea aphid, Acyrthosiphon pisum, encompasses distinct host races specialized
      on various Fabaceae species, but the extent of genetic divergence associated with
      ecological specialization varies greatly depending on plant and geographic
      origins of aphid populations. Here, we studied the genetic structure of French
      sympatric pea aphid populations collected on perennial (pea and faba bean) and
      annual (alfalfa and red clover) hosts using 14 microsatellite loci. Classical and
      Bayesian population genetics analyses consistently identified genetic clusters
      mostly related to plant origin: the pea/faba bean cluster was highly divergent
      from the red clover and the alfalfa ones, indicating they represent different
      stages along the continuum of genetic differentiation. Some genotypes were
      assigned to a cluster differing from the one expected from their plant origin
      while others exhibited intermediate genetic characteristics. These results
      suggest incomplete barriers to gene flow. However, this limited gene flow seems
      insufficient to prevent ecological specialization and genetic differentiation in
      sympatry.

PMID- 16599916
TI  - Genetic caste determination in Pogonomyrmex harvester ants imposes costs during
      colony founding.
AB  - Some populations of Pogonomyrmex harvester ants comprise genetically
      differentiated pairs of interbreeding lineages. Queens mate with males of their
      own and of the alternate lineage and produce pure-lineage offspring which develop
      into queens and inter-lineage offspring which develop into workers. Here we
      tested whether such genetic caste determination is associated with costs in terms
      of the ability to optimally allocate resources to the production of queens and
      workers. During the stage of colony founding, when only workers are produced,
      queens laid a high proportion of pure-lineage eggs but the large majority of
      these eggs failed to develop. As a consequence, the number of offspring produced
      by incipient colonies decreased linearly with the proportion of pure-lineage eggs
      laid by queens. Moreover, queens of the lineage most commonly represented in a
      given mating flight produced more pure-lineage eggs, in line with the view that
      they mate randomly with the two types of males and indiscriminately use their
      sperm. Altogether these results predict frequency-dependent selection on pairs of
      lineages because queens of the more common lineage will produce more pure-lineage
      eggs and their colonies be less successful during the stage of colony founding,
      which may be an important force maintaining the coexistence of pairs of lineages
      within populations.

PMID- 16599917
TI  - Coevolution of male and female reproductive traits in a simultaneously
      hermaphroditic land snail.
AB  - Inter- and intraspecific studies in gonochoristic animals reveal a covariation
      between sperm characteristics and the size of the female reproductive tract,
      indicating a rapid evolutionary divergence, which is consistent with the theory
      of post-copulatory sexual selection. Simultaneous hermaphrodites differ from
      species with separate sexes (gonochorists) in that they possess both functional
      male and female reproductive organs at the same time. We investigated whether in
      hermaphroditic animals intraspecific variation in reproductive traits results
      from divergent coevolution, by quantifying the variation in male and female
      traits among six natural populations of the snail Arianta arbustorum and
      examining the covariation in interacting traits. There was a significant among
      population variation in spermatophore volume, number of sperm transferred and
      sperm length, as well as in volume of the sperm storage organ (spermatheca) and
      number of tubules, but not in spermatheca length. We found a positive association
      between sperm number transferred and spermatheca volume. This result suggests
      that the same post-copulatory mechanisms as in gonochorists drive the correlated
      evolution of reproductive characters in hermaphrodites.

PMID- 16599919
TI  - Ornaments or offspring? Female sticklebacks (Gasterosteus aculeatus L.) trade off
      carotenoids between spines and eggs.
AB  - Hypotheses and models to explain female ornaments often assume that the
      elaborated traits are condition dependent; nevertheless, few empirical studies
      have addressed this topic. We studied a population of three-spined sticklebacks
      (Gasterosteus aculeatus) in which the females have conspicuous, carotenoid-based
      red coloration to their pelvic spines. The red coloration seems not to be
      condition dependent, as coloration is negatively associated with age and body
      length and not associated with condition. Furthermore, redder females did not
      have a lower density of leucocytes. We found a negative association between the
      females' red carotenoid-based coloration in the spines and the amount of
      carotenoids in the female's gonads. Males choosing red-coloured females will
      fertilize eggs with small amounts of carotenoids and appear not to gain any
      benefit from their mates' phenotypic quality that could result in offspring of
      improved quality. These results do not support the 'direct selection hypothesis'
      to explain the existence of the female ornaments.

PMID- 16599920
TI  - Combined influence of maternal and paternal quality on sex allocation in red
      capped robins.
AB  - Sex allocation theory predicts females will adaptively manipulate sex ratios to
      maximize their progeny's reproductive value. Recently, the generality of biased
      sex allocation in birds has been questioned by meta-analytic reviews, which
      demonstrate that many previously reported significant results may simply reflect
      sampling error. Here, we utilize a robust sample size and powerful statistical
      approach to determine whether parental quality is correlated with biased sex
      allocation in red-capped robins. Indices of maternal quality (including
      interactive effects of age and condition) were strongly related to sex
      allocation. These relationships were in the predicted directions, with larger
      effect sizes than those of previous studies in this field. There were also
      paternal correlates, involving age and the source of paternity. We propose that
      biased sex allocation occurs in this species, and is maintained by differing
      production costs of each sex and genetic benefits to females of producing sons
      when fertilized by high-quality males.

PMID- 16599918
TI  - Evidence for cryptic glacial refugia from North American mountain sheep
      mitochondrial DNA.
AB  - The separation of populations by ice sheets into large refugia can account for
      much of the genetic diversity found in present day populations. The evolutionary
      implications of small glacial refugia have not been as thoroughly explored. To
      examine refugial origins of North American mountain sheep Ovis spp., we analyzed
      a 604 bp portion of the mitochondrial DNA (mtDNA) control region from 223 O.
      dalli and O. canadensis. Major refugia were identified in eastern Beringia and
      southern North America, and we found evidence for two smaller refugia situated
      between the Laurentide and Cordilleran glaciers. Our results are the first to
      demonstrate support for survival of any organism in the latter two refugia. These
      refugia also appear to have conserved a genetic signal that confirms past
      hybridization of O. dalli and O. canadensis.

PMID- 16599921
TI  - Predator-induced phenotypic plasticity in tadpoles: extension or innovation?
AB  - Phenotypic plasticity, the ability of a trait to change as a function of the
      environment, is central to many ideas in evolutionary biology. A special case of
      phenotypic plasticity observed in many organisms is mediated by their natural
      predators. Here, we used a predator-prey system of dragonfly larvae and tadpoles
      to determine if predator-mediated phenotypic plasticity provides a novel way of
      surviving in the presence of predators (an innovation) or if it represents a
      simple extension of the way noninduced tadpoles survive predation. Tadpoles of
      Limnodynastes peronii were raised in the presence and absence of predation, which
      then entered a survival experiment. Induced morphological traits, primarily tail
      height and tail muscle height, were found to be under selection, indicating that
      predator-mediated phenotypic plasticity may be adaptive. Although predator
      induced animals survived better, the multivariate linear selection gradients were
      similar between the two tadpole groups, suggesting that predator-mediated
      phenotypic plasticity is an extension of existing survival strategies. In
      addition, nonlinear selection gradients indicated a cost of predator-induced
      plasticity that may limit the ability of phenotypic plasticity to enhance
      survival in the presence of predators.

PMID- 16599922
TI  - Divergence in the calling songs between sympatric and allopatric populations of
      the southern wood cricket Gryllus fultoni (Orthoptera: Gryllidae).
AB  - In the eastern United States the wood cricket Gryllus fultoni (Orthoptera:
      Gryllidae) occurs in sympatry with G. vernalis in an area between eastern Kansas
      and west of the Appalachian Mountains. Calling songs were recorded from 13
      sympatric and allopatric localities. Both field and laboratory recordings showed
      that chirp rate (CR) and pulse rate (PR) overlapped extensively between
      allopatric populations of G. fultoni and sympatric populations of G. vernalis; by
      contrast, there was little or no overlap in these variables between sympatric
      populations of these two species. Divergence in PR and CR between the two species
      was thus greater in areas of sympatry than in areas of allopatry. Our field and
      laboratory studies of G. fultoni calling songs thus demonstrate the pattern
      expected of character displacement and support the genetic assumptions of this
      hypothesis. Other possible explanations for the sympatric divergence such as
      ecological character displacement and clinal variation are discussed.

PMID- 16599923
TI  - Altitudinal patterns for latitudinally varying traits and polymorphic markers in
      Drosophila melanogaster from eastern Australia.
AB  - Altitudinal changes in traits and genetic markers can complement the studies on
      latitudinal patterns and provide evidence of natural selection because of
      climatic factors. In Drosophila melanogaster, latitudinal variation is well known
      but altitudinal patterns have rarely been investigated. Here, we examine five
      traits and five genetic markers on chromosome 3R in D. melanogaster collected at
      high and low altitudes from five latitudes along the eastern coast of Australia.
      Significant altitudinal differentiation was observed for cold tolerance,
      development time, ovariole number in unmated females, and the microsatellite
      marker DMU25686. Differences tended to match latitudinal patterns, in that trait
      values at high altitudes were also found at high latitudes, suggesting that
      factors linked to temperature are likely selective agents. Cold tolerance was
      closely associated with average temperature and other climatic factors, but no
      significant associations were detected for the other traits. Genes around
      DMU25686 represent good candidates for climatic adaptation.

PMID- 16599924
TI  - Dynamics of host plant use and species diversity in Polygonia butterflies
      (Nymphalidae).
AB  - The ability of insects to utilize different host plants has been suggested to be
      a dynamic and transient phase. During or after this phase, species can shift to
      novel host plants or respecialize on ancestral ones. Expanding the range of host
      plants might also be a factor leading to higher levels of net speciation rates.
      In this paper, we have studied the possible importance of host plant range for
      diversification in the genus Polygonia (Nymphalidae, Nymphalini). We have
      compared species richness between sistergroups in order to find out if there are
      any differences in number of species between clades including species that
      utilize only the ancestral host plants ('urticalean rosids') and their
      sisterclades with a broader (or in some cases potentially broader) host plant
      repertoire. Four comparisons could be made, and although these are not all
      phylogenetically or statistically independent, all showed clades including
      butterfly species using other or additional host plants than the urticalean
      rosids to be more species-rich than their sisterclade restricted to the ancestral
      host plants. These results are consistent with the theory that expansions in host
      plant range are involved in the process of diversification in butterflies and
      other phytophagous insects, in line with the general theory that plasticity may
      drive speciation.

PMID- 16599925
TI  - On hidden heterogeneity in directional asymmetry--can systematic bias be avoided?
AB  - Directional asymmetry (DA) biases the analysis of fluctuating asymmetry (FA)
      mainly because among-individual differences in the predisposition for DA are
      difficult to detect. However, we argue that systematic bias mainly results from
      predictable associations between signed right-left asymmetry and other factors,
      i.e. from systematic variation in DA. We here demonstrate methods to test and
      correct for this, by analysing bilateral asymmetry in size and shape of an
      irregular sea urchin. Notably, in this model system, DA depended significantly on
      body length and geographic origin, although mean signed asymmetry (mean DA) was
      not significant in the sample as a whole. In contrast to the systematic variation
      in DA, undetectable, random variability in the underlying DA mainly leads to
      reduced statistical power. Using computer simulations, we show that this loss of
      power is probably slight in most circumstances. We recommend future studies on FA
      to routinely test and correct for not only as yet for mean DA, but also for
      systematic variation in DA.

PMID- 16599927
TI  - Host use of a hemiparasitic plant: no trade-offs in performance on different
      hosts.
AB  - To examine putative specialization of a hemiparasitic plant to the most
      beneficial host species, we studied genetic variation in performance and trade
      offs between performance on different host species in the generalist
      hemiparasite, Rhinanthus serotinus. We grew 25 maternal half-sib families of the
      parasite on Agrostis capillaris and Trifolium pratense and without a host in a
      greenhouse. Biomass and number of flowers of the parasite were the highest when
      grown on T. pratense. There were significant interactions between host species
      and R. serotinus seed-family indicating that the differences in performance on
      the two hosts and without a host varied among the families. However, we found no
      significant negative correlations between performance of R. serotinus on the host
      species or between performance on the two hosts and autotrophic performance.
      Thus, the genetic factors studied here are not likely to affect the evolution of
      specialization of R. serotinus to the most beneficial host.

PMID- 16599926
TI  - Evolution of habitat-dependent sex allocation in plants: superficially similar
      to, but intrinsically different from animals.
AB  - Because pollen disperses and ovules do not, a basic difference in dispersal
      abilities of male and female gametes exists in plants. With an analytical model,
      we show that the combination of such sex-biased dispersal of gametes and
      variation of habitat quality results in two opposite selective forces acting on
      the evolution of sex allocation in plants: (i) a plant should overproduce pollen
      in good patches and overproduce ovules in poor patches in order to equilibrate
      secondary sex ratios of gametes after pollen dispersal; (ii) a plant should
      overproduce ovules in good patches and overproduce pollen in poor patches in
      order to increase the likelihood that its progeny establishes in good patches.
      Our theoretical results indicate that the evolution of habitat-dependent sex
      allocation should be favoured in plants, in a direction that depends on the
      relative dispersal ability of pollen and seeds. We also show that superficially
      similar predictions obtained for habitat-dependent evolutionarily stable sex
      allocation in animals actually result from a completely different balance between
      the two underlying evolutionary forces.

PMID- 16599928
TI  - Does selection by resistant hosts trigger local adaptation in plant-pathogen
      systems?
AB  - Understanding the consequences of selection by host resistance on pathogen
      population structure provides useful insights into the dynamics of host-parasite
      co-evolution processes and is crucial for effective disease management through
      resistant cultivars. We tested general vs. local population adaptation to host
      cultivars, by characterizing a French collection of Phytophthora infestans (the
      causal organism of potato late blight) sampled during two consecutive years on
      cultivars exhibiting various levels of resistance. Local populations were
      structured by the host for virulence (qualitative pathogenicity) but also for
      aggressiveness (quantitative pathogenicity). All populations had a low genotypic
      diversity for amplified fragment length polymorphisms (AFLPs), and presumably
      consisted of a few closely related clonal lineages. No correlation was detected
      between pathogenicity traits and AFLP genotypes. The data support the hypothesis
      of general adaptation for aggressiveness, to which directional selection for
      virulence is superimposed when race-specific resistance is introduced.

PMID- 16599929
TI  - Genotype x environment interaction for male attractiveness in an acoustic moth:
      evidence for plasticity and canalization.
AB  - The lek paradox arises when choosy females deplete the genetic variance for male
      display traits from a population, yet substantial additive genetic variation
      (V(A)) in male traits persists. Thus, the lek paradox can be more generally
      stated as one of the most fundamental evolutionary questions: What maintains
      genetic variation in natural populations? One solution to this problem may be
      found in the condition-dependent nature of many sexually selected traits.
      Genotype x environment (G x E) interactions can maintain V(A) under conditions of
      environmental heterogeneity provided certain restrictions are met, although
      antagonistic pleiotropy has also been proposed as a mechanism. Here, we provide
      evidence for G x E interactions and against the role of antagonistic pleiotropy
      in the maintenance of V(A) for sexually selected traits. Using inbred lines of
      the lesser waxmoth Achroia grisella, we measured V(A) for song attractiveness,
      condition and development rate under different competitive environments and found
      that genotypes differed in their plasticity. We argue that variation persists in
      natural populations because G x E interactions prevent any one variant from
      producing the optimal phenotype across all environments.

PMID- 16599930
TI  - A quantitative trait locus for recognition of foreign eggs in the host of a brood
      parasite.
AB  - Avian brood parasites reduce the reproductive output of their hosts and thereby
      select for defence mechanisms such as ejection of parasitic eggs. Such defence
      mechanisms simultaneously select for counter-defences in brood parasites, causing
      a coevolutionary arms race. Although coevolutionary models assume that defences
      and counter-defences are genetically influenced, this has never been demonstrated
      for brood parasites. Here, we give strong evidence for genetic differences
      between ejector and nonejectors, which could allow the study of such host defence
      at the genetic level, as well as studies of maintenance of genetic variation in
      defences. Briefly, we found that magpies, that are the main host of the great
      spotted cuckoo in Europe, have alleles of one microsatellite locus (Ase64) that
      segregate between accepters and rejecters of experimental parasitic eggs.
      Furthermore, differences in ejection rate among host populations exploited by the
      brood parasite covaried significantly with the genetic distance for this locus.

PMID- 16599931
TI  - In search of clinal variation in the period and clock timing genes in Australian
      Drosophila melanogaster populations.
AB  - Clinal variation for repeat number in the Thr-Gly region of the period circadian
      timing gene in Drosophila melanogaster was described in Europe and has
      subsequently been used as evidence of thermal selection on period alleles. To
      test for clinal variation in this gene along the east coast of Australia, the
      period polymorphism was scored on flies from multiple samples collected
      repeatedly over a 5-year interval, along with variation at another circadian
      rhythm locus, clock. For period, there was no consistent evidence of clinal
      variation in the 17 and/or 20 repeat alleles, although when average allele length
      was examined a weak consistent clinal pattern was detected. For clock there was
      no evidence of clinal variation in the two most common alleles or in average
      repeat size. These data are inconsistent with the reported patterns in Europe and
      suggest that clinal variation in timing genes needs to be re-examined in this
      region.

PMID- 16599932
TI  - Correlations between heterozygosity and measures of genetic similarity:
      implications for understanding mate choice.
AB  - There is currently considerable interest in testing the effects of genetic
      compatibility and heterozygosity on animal mate preferences. Evidence for either
      effect is rapidly accumulating, although results are not always clear-cut.
      However, correlations between mating preferences and either genetic similarity or
      heterozygosity are usually tested independently, and the possibility that
      similarity and heterozygosity may be confounded has rarely been taken into
      account. Here we show that measures of genetic similarity (allele sharing,
      relatedness) may be correlated with heterozygosity, using data from 441 human
      individuals genotyped at major loci in the major histocompatibility complex, and
      281 peafowl (Pavo cristatus) individuals genotyped at 13 microsatellite loci. We
      show that average levels of allele sharing and relatedness are each significantly
      associated with heterozygosity in both humans and peafowl, that these
      relationships are influenced by the level of polymorphism, and that these
      similarity measures may correlate with heterozygosity in qualitatively different
      ways. We discuss the implications of these inter-relationships for interpretation
      of mate choice studies. It has recently become apparent that mating preferences
      for 'good genes' and 'compatible genes' may introduce discordant choice amongst
      individuals, since the optimal mate for one trait may not be optimal for the
      other, and our results are consistent with this idea. The inter-relationship
      between these measures of genetic quality also carries implications for the way
      in which mate choice studies are designed and interpreted, and generates
      predictions that can be tested in future research.

PMID- 16599933
TI  - Does competitive divergence occur if assortative mating is costly?
AB  - Most models of sympatric speciation have assumed that assortative mating has no
      costs. A few studies, however, have shown that the costs for being choosy can
      prevent such speciation. Here, we investigate the role of the strength of
      assortment and of the costs for being choosy for a simple genetic model of a
      single ('magic') trait that mediates both intraspecific competition for a
      continuum of resources and assortative mating, which is induced by choosy females
      who preferentially mate with males of similar phenotype. Choosiness may be costly
      if it is difficult to find a mating partner. Such magic trait models are
      considered to be most conducive of sympatric speciation. We consider a sexually
      reproducing population of haploid individuals that is density regulated. The
      trait is determined by a single locus with multiple alleles. The strength of
      stabilizing selection (caused by a unimodal resource distribution), the strength
      of competition, the degree of assortment and the costs for being choosy are
      independent parameters. We investigate analytically and numerically how these
      parameters determine the equilibrium and stability structure. In particular, we
      identify conditions under which no polymorphism at all is maintained as well as
      conditions under which strong competitive divergence occurs, or the population
      even splits into two reproductively isolated classes of highly diverse
      phenotypes. If costs are absent or moderate, genetic variability tends to be
      minimized at intermediate strengths of assortment, and reproductively isolated
      classes of phenotypes are a likely result of evolution only for intermediate or
      strong competition and for very strong assortment. The likelihood of divergence
      depends relatively weakly on the costs as long as they are not high. With high
      costs, however, increasingly strong assortment rapidly depletes all genetic
      variation, and strong competitive divergence is prevented.

PMID- 16599934
TI  - Stable genetic polymorphism in heterogeneous environments: balance between
      asymmetrical dispersal and selection in the acorn barnacle.
AB  - Elucidating the processes responsible for maintaining polymorphism at
      ecologically relevant genes is intimately related to understanding the interplay
      between selection imposed by habitat heterogeneity and a species' capacity for
      dispersal in the face of environmental constraints. In this paper, we used a
      model-based approach to solve equilibria of balanced polymorphism, given values
      of fitness and larval dispersal among different habitats in the acorn barnacle
      Semibalanus balanoides from the Gulf of St Lawrence. Our results showed that
      allele frequencies observed at both MPI* and GPI* loci represented stable
      equilibria, given empirical estimates of fitness values, and that considerably
      more larvae dispersed from one region (north) to the other (south) than vice
      versa. Dispersal conditions were predicted to be similar for the maintenance of
      polymorphism at both loci. Moreover, the values of asymmetrical dispersal
      required by the model to reach stable equilibria were compatible with empirical
      estimates of larval dispersal and oceanic circulation documented in this system.
      Overall, this study illustrated the usefulness of a modified and computable
      version of Bulmer's model (1972) in order to test hypotheses of balanced
      polymorphism resulting from interactions between spatial selection and
      asymmetrical dispersal.

PMID- 16599936
TI  - No evidence for survival selection on carotenoid-based nestling coloration in
      great tits (Parus major).
AB  - In several vertebrate species evidence supports the hypothesis that carotenoid
      based coloration of adults has evolved due to sexual selection. However, in some
      birds already the nestlings display carotenoid-based coloration. Because the
      nestling's body plumage is typically moulted before the first reproductive event,
      sexual selection cannot explain the evolution of these carotenoid-based traits.
      This suggests that natural selection might be the reason for its evolution. Here
      we test whether the carotenoid-based nestling coloration of great tits (Parus
      major) predicts survival after fledging. Contrary to our expectation, the
      carotenoid-based plumage coloration was not related to short- nor to long-term
      survival in the studied population. Additionally, no prefledging selection was
      detectable in an earlier study. This indicates that the carotenoid-based
      coloration of nestling great tits is currently not under natural selection and it
      suggests that past selection pressures or selection acting on correlated traits
      may have led to its evolution.

PMID- 16599935
TI  - Genetics of sex pheromone blend differences between Heliothis virescens and
      Heliothis subflexa: a chromosome mapping approach.
AB  - Males of the noctuid moths, Heliothis virescens and H. subflexa locate mates
      based on species-specific responses to female-emitted pheromones that are
      composed of distinct blends of volatile compounds. We conducted genetic crosses
      between these two species and used AFLP marker-based mapping of backcross
      families (H. subflexa direction) to determine which of the 30 autosomes in these
      moths contained quantitative trait loci (QTL) controlling the proportion of
      specific chemical components in the pheromone blends. Presence/absence of single
      H. virescens chromosomes accounted for 7-34% of the phenotypic variation among
      backcross females in seven pheromone components. For a set of three similar 16
      carbon acetates, two H. virescens chromosomes interacted in determining their
      relative amounts within the pheromone gland and together accounted for 53% of the
      phenotypic variance. Our results are discussed relative to theories about
      population genetic processes and biochemical mechanisms involved in the evolution
      of new sexual communication systems.

PMID- 16599937
TI  - Tempo, mode and phylogenetic associations of relative embryo size evolution in
      angiosperms.
AB  - Relative embryo size (E : S, the ratio of embryo to seed) is a key trait related
      to germination ecology and seed plant evolution. A small, underdeveloped embryo
      is a primitive feature of angiosperms, which has led to the hypothesis that an
      evolutionary trend towards increasing E : S has occurred. Here, I examine first
      the tempo and mode of E : S evolution in angiosperms; then I test for
      phylogenetic associations of E : S with traits hypothetically related to
      anagenetic (germination time) and cladogenetic (number of species per family and
      differential speciation) change, and finally I test the existence of a
      directional increasing trend in E : S. The analysis of the evolutionary tempo
      suggests that E : S changed very fast early in evolutionary time and remained
      stable later, which is consistent with early radiations and fits well with the
      history of angiosperms consisting of rapid spread associated with great
      diversification rates soon after their origin. E : S evolution in angiosperms has
      not followed a punctuational mode of evolution but a scaled-gradualism evolution
      in which stasis has occurred in longer branches of the phylogeny. An evolutionary
      trend towards increasing E : S has not been actively driven by anagenesis nor
      cladogenesis, although large E : S is associated with high levels of
      diversification (i.e. number of species per family). This rapid ecological
      diversification occurring in the early radiation probably produced an increasing
      phenotypic variance in the E : S. Because the ancestral embryo was so small, an
      increase in variance might have produced a passive trend towards the only
      direction allowed for the ancestral embryo to evolve. Thus, a passive diffusion
      away from a lower bound may explain the average increase in E : S.

PMID- 16599938
TI  - Unique genomic configuration revealed by microsatellite DNA in polyploid
      dogroses, Rosa sect. Caninae.
AB  - An allopolyploid complex with high genomic integrity has been studied. Dogroses
      transmit only seven chromosomes (from seven bivalents) through the pollen,
      whereas 21, 28 or 35 chromosomes (from seven bivalents and 14, 21 or 28
      univalents) come from the egg cells. Seedlings derived from two interspecific
      crosses were analysed with flow cytometry and molecular markers to determine
      ploidy level, mode of reproduction and genomic constitution. Evidence was
      obtained for the formation of unreduced male and female gametes, which can take
      part in fertilization (producing seedlings with higher ploidy than the parental
      plants) or in apomictic reproduction. Random amplified polymorphic DNA (RAPD) and
      microsatellite analyses indicated that three seedlings (5%) were derived through
      apomixis, whereas the other 49 were hybrids. Bivalent formation appears to
      involve chromosomes that consistently share the same microsatellite alleles.
      Allele-sharing between the maternally transmitted and highly conserved univalent
      forming chromosomes reflected the taxonomic distance between different genotypes.
      The frequently recombining bivalent-forming chromosomes were taxonomically less
      informative.

PMID- 16599939
TI  - Negatively condition dependent predation cost of a positively condition dependent
      sexual signalling.
AB  - Predation is considered as an important factor constraining the expression of
      sexual signals. Nevertheless, direct quantitative evidence for predation
      provoking significant viability costs on individuals signalling at high rates is
      scarce. Moreover, it is unclear whether high rate signallers are able to balance
      presumably increased predation costs. We examined whether a condition dependent
      audible sexual signal, drumming, makes Hygrolycosa rubrofasciata male spiders
      more prone to predation by pied flycatchers (Ficedula hypoleuca), and whether
      sexual signalling rate is related to escaping ability once attacked. When birds
      were given a choice between two spider males manipulated to drum either one or
      three bouts per minute using playbacks, naive birds attacked the males randomly
      regardless of the drumming rate. However, experienced birds chose significantly
      more often the males with high signalling rate. When spiders were allowed to
      escape, males with high sexual signalling rate tended to be better at escaping
      attacks than males with low sexual signalling rate. This study provides evidence
      that high signalling rate increases the risk of predation, but simultaneously
      males with high mobility, which correlates positively with signalling rate seemed
      to be better at compensating this cost.

PMID- 16599940
TI  - Quantification of Alzheimer pathology in ageing and dementia: age-related
      accumulation of amyloid-beta(42) peptide in vascular dementia.
AB  - Clinicopathological observations suggest there is considerable overlap between
      vascular dementia (VaD) and Alzheimer's disease (AD). We used immunochemical
      methods to compare quantities of amyloid-beta (Abeta) peptides in post mortem
      brain samples from VaD, AD subjects and nondemented ageing controls. Total Abeta
      peptides extracted from temporal and frontal cortices were quantified using a
      previously characterized sensitive homogenous time-resolved fluorescence (HTRF)
      assay. The HTRF assays and immunocapture mass spectrometric analyses revealed
      that the Abeta(42) species were by far the predominant form of extractable
      peptide compared with Abeta(40) peptide in VaD brains. The strong signal
      intensity for the peak representing Abeta(4-42) peptide confirmed that these N
      terminally truncated species are relatively abundant. Absolute quantification by
      HTRF assay showed that the mean amount of total Abeta(42) recovered from VaD
      samples was approximately 50% of that in AD, and twice that in the age-matched
      controls. Linear correlation analysis further revealed an increased accumulation
      with age of both Abeta peptides in brains of VaD subjects and controls.
      Interestingly, VaD patients surviving beyond 80 years of age exhibited comparable
      Abeta(42) concentrations with those in AD in the temporal cortex. Our findings
      suggest that brain Abeta accumulates increasingly with age in VaD subjects more
      so than in elderly without cerebrovascular disease and support the notion that
      they acquire Alzheimer-like pathology in older age.

PMID- 16599941
TI  - Specific association of small heat shock proteins with the pathological hallmarks
      of Alzheimer's disease brains.
AB  - The small heat shock protein family (sHsp) comprises molecular chaperones able to
      interact with incorrectly folded proteins. Alzheimer's disease (AD) is
      characterized by pathological lesions such as senile plaques (SPs), cerebral
      amyloid angiopathy (CAA) and neurofibrillary tangles (NFTs), predominantly
      consisting of the incorrectly folded proteins amyloid-beta (Abeta) and tau
      respectively. The aim of this study was to investigate the association of the
      chaperones Hsp20, HspB2, alphaB-crystallin and Hsp27 with the pathological
      lesions of AD brains. For this purpose, a panel of well-characterized antibodies
      directed against these sHsps was used in immunohistochemistry and immunoblotting.
      We observed extracellular expression of Hsp20, Hsp27 and HspB2 in classic SPs,
      and Hsp20 expression in diffuse SPs. In addition, extracellular expression of
      HspB2 was observed in CAA. Both Hsp27 and alphaB-crystallin were also observed in
      astrocytes associated with both SPs and CAA. Furthermore, none of the sHsps were
      observed in NFTs in AD brains. We conclude that specific sHsp species may be
      involved in the pathogenesis of either SPs or CAA in AD.

PMID- 16599942
TI  - Rarity of JC virus DNA sequences and early proteins in human gliomas and
      medulloblastomas: the controversial role of JC virus in human neurooncogenesis.
AB  - JC virus (JCV), the agent of progressive multifocal leucoencephalopathy (PML),
      exerts an oncogenic effect in several laboratory animal models. Moreover, JCV
      genomic DNA and early viral protein T-antigen have been detected in various types
      of human central nervous system (CNS) neoplasms. To further explore this
      association we have studied paraffin-embedded brain biopsy tissue from 60
      neoplasms (55 gliomas and five medulloblastomas) and 15 reactive gliosis cases
      for the presence of JCV DNA sequences and proteins. Four post mortem cases of HIV
      associated PML were used as positive controls. Samples were assessed by
      polymerase chain reaction (PCR) amplification of early (large T antigen) and late
      (virion protein 3) sequences and immunohistochemistry (IHC) with both PAb 2024
      and anti-SV40 large T antigen monoclonal antibodies. Five cases (three neoplasms
      and two reactive gliosis instances) showed low viral DNA levels when PCR-tested
      for VP3 or large T, while no case was immunoreactive for any of the two
      antibodies used. The four PML cases yielded positive results with both PCR and
      IHC. Additionally, IHC with both antibodies was applied to a tissue micro-array
      including 109 CNS tumours and 21 reactive gliosis samples. No immunoreactivity
      was detected in any of these tissue micro-array samples. The rarity of JCV DNA
      sequences and early proteins in our brain tumours enriches the controversy over
      the role of JCV in human neurooncogenesis, whose clarification is in need of
      further molecular and epidemiologic studies.

PMID- 16599943
TI  - Serine proteases purified from sera of patients with amyotrophic lateral
      sclerosis (ALS) induce contrasting cytopathology in murine motoneurones to IgG.
AB  - Affinity purified IgG from sera of patients with amyotrophic lateral sclerosis
      (ALS) is claimed to enhance transmitter release, induce apoptotic death of
      cultured motoneurones, and elicit a distinctive cytopathology with raised Ca(2+)
      in mouse motoneurones. An alternative hypothesis attributes these events to
      serine proteases in ALS sera. To test this, motoneurones in BALB/c mice injected
      intraperitoneally with plasminogen affinity purified from sera of ALS patients
      and healthy controls were analysed using immunochemical and ultrastructural
      morphometric methods. The responses were validated in motoneurones of mice
      injected with commercially purified plasminogen, tissue plasminogen activator
      (tPA), or plasmin. Motoneurones in non-injected mice had normal morphology and
      ultrastructure without evidence of electron-dense degeneration. Purified
      plasminogen from both ALS patients and healthy controls, evoked electron-dense
      motoneurone degeneration, as did commercially purified plasminogen and tPA. The
      common cytopathology comprised disruption and distension of Nissl body rough
      endoplasmic reticulum, cytoplasmic polyribosomal proliferation, and significant
      Ca(2+) enhancement in mitochondria. By contrast, using affinity purified serum
      immunoglobulins, ALS-IgG but not IgG from healthy or disease controls, elicited
      necrosis, with 30% of ALS-IgGs tested evoking electron-dense degeneration in 40%
      of motoneurones. The primary cytopathology was extensive swelling of Golgi
      endoplasmic reticulum and mitochondria, with enhancement of Ca(2+) in Golgi
      endoplasmic reticulum and presynaptic boutons. We conclude that serine proteases
      purified from sera of ALS patients elicits a distinctive cytopathology and
      pattern of Ca(2+) enhancement in motoneurones different from that found on
      passive transfer of affinity purified ALS-IgG.

PMID- 16599944
TI  - Changed distribution pattern of the constitutive rather than the inducible HSP70
      chaperone in neuromelanin-containing neurones of the Parkinsonian midbrain.
AB  - Aberrant protein aggregation has been recognized as an important factor in the
      degeneration of melanized dopaminergic neurones in Parkinson's disease (PD). The
      constitutive (HSP73) and (heat)-inducible (HSP72) proteins of the heat shock 70
      family form a major defence system against pathological protein aggregation.
      However, the distribution patterns of these chaperones in nigral neuromelanin
      laden neurones are largely unknown. The present study determined the distribution
      of HSP72 and HSP73 in control and Parkinsonian substantia nigra, using
      immunohistochemistry. In the neuromelanin-laden neurones of controls, HSP72 was
      nondetectable, whereas HSP73 was weakly expressed in both the cytosol and the
      nucleus. Surprisingly, in PD subjects, marked nuclear HSP73, but not HSP72
      immunoreactivity was observed, while cytosolic immunoreactivity of the two
      chaperones resembled the labelling pattern observed in controls. Furthermore,
      HSP73 immunoreactivity was observed in a subset of the Lewy bodies (LBs) detected
      in the substantia nigra of PD subjects, whereas only few of these LBs were
      labelled with HSP72. Interestingly, HSP72 and to a lesser extent HSP73
      immunoreactivity was much stronger in nonmelanized neurones as compared with
      melanized neurones in this area. Thus, we conclude that the distribution pattern
      of HSP73 rather than HSP72 is changed in the nigral neuromelanin-laden neurones
      of PD subjects as compared with control subjects. The impaired ability of aged,
      dopaminergic neurones to express high levels of chaperones, may contribute to the
      preferential vulnerability of the latter cells in PD.

PMID- 16599945
TI  - Iron overload and antioxidative role of perivascular astrocytes in
      aceruloplasminemia.
AB  - Aceruloplasminemia (ACP) is an inherited disorder of iron metabolism caused by
      the lack of ceruloplasmin activity; the neuropathological hallmarks are excessive
      iron deposition, neuronal loss, bizarrely deformed astrocytes, and numerous
      'grumose or foamy spheroid bodies (GFSBs)'. We histopathologically examined two
      autopsied ACP brains, and observed for the first time that GFSBs form in clusters
      at the ends of perivascular astrocytic foot processes. Both the deformed
      astrocytes and the GFSBs contained ferric iron and were intensely immunolabelled
      with antibodies against the antioxidant proteins ferritin and manganese
      superoxide dismutase (Mn SOD). Ceruloplasmin is largely produced by perivascular
      astrocytes in the central nervous system and exhibits a ferroxidase activity that
      inhibits iron-associated lipid peroxidation and hydroxyl radical formation;
      therefore, the lack of ceruloplasmin causes direct oxidative stress on
      astrocytes. The intense immunolabelling of ferritin and Mn SOD most likely
      reflects a defensive response to iron-mediated oxidative stress. This study
      suggests that astrocytes play key roles in iron trafficking and the
      detoxification of iron-mediated free radicals at the blood-brain barrier and in
      the parenchyma in ACP brain. The antioxidative ability of astrocytes is one of
      their essential neuroprotective effects, and the decompensation of this ability
      may lead to secondary neuronal cell death in ACP.

PMID- 16599946
TI  - Behavioural and histopathological alterations in mice with cerebral malaria.
AB  - Different features of sensorimotor function and behaviour were studied in murine
      cerebral malaria (CM) and malaria without cerebral involvement (non-CM) applying
      the primary screen of the SHIRPA protocol. Histopathological analysis of distinct
      brain regions was performed and the relative size of haemorrhages and plugging of
      blood cells to brain vasculature was analysed. Animals suffering from CM develop
      a wide range of behavioural and functional alterations in the progressive course
      of the disease with a statistically significant impairment in all functional
      categories assessed 36 h prior to death when compared with control animals. Early
      functional indicators of cerebral phenotype are impairments in reflex and sensory
      system and in neuropsychiatric state. Deterioration in function is paralleled by
      the degree of histopathological changes with a statistically significant
      correlation between the SHIRPA score of CM animals and the mean size of brain
      haemorrhage. Furthermore, image analysis yielded that the relative area of the
      brain lesions was significantly larger in the forebrain and brainstem compared
      with the other regions of interest. Our results indicate that assessment of
      sensory and motor tasks by the SHIRPA primary screen is appropriate for the early
      in vivo discrimination of cerebral involvement in experimental murine malaria.
      Our findings also suggest a correlation between the degree of functional
      impairment and the size of the brain lesions as indicated by parenchymal
      haemorrhage. Applying the SHIRPA protocol in the functional characterization of
      animals suffering from CM might prove useful in the preclinical assessment of new
      antimalarial and potential neuroprotective therapies.

PMID- 16599948
TI  - Papillary tumour of the pineal region: histodiagnostic considerations.

PMID- 16599947
TI  - In vitro identification and functional characterization of glial precursor cells
      in human gliomas.
AB  - Human gliomas including astrocytomas and oligodendrogliomas are defined as being
      composed of neoplastic astrocytes and oligodendrocytes respectively. Here, on the
      basis of in vitro functional assays, we show that gliomas contain a mixture of
      glial progenitor cells and their progeny. We have set up explant cultures from
      pilocytic astrocytomas, glioblastomas and oligodendrogliomas and studied antigens
      that characterize glial lineage, from the precursor cells (glial restricted
      precursors and oligodendrocyte-type2-astrocyte/oligodendrocyte precursor cells
      expressing the A2B5 ganglioside) to the differentiated cells (oligodendrocyte and
      type-1 and type-2 astrocytes). All tumoral explants contain A2B5+ cells and can
      generate migrating cells with distinctive functional properties according to
      glioma subtypes. In pilocytic astrocytomas, very few migrating cells are dividing
      and can differentiate in type-2 astrocytes or towards the oligodendrocyte
      lineage. In glioblastomas, most migrating cells are dividing, express A2B5 or
      glial fibrillary acid protein (GFAP) and can generate oligodendrocytes and type-1
      and type-2 astrocytes in appropriate medium. Oligodendroglioma explants are made
      by actively dividing glial precursor cells expressing A2B5 or PSA-NCAM. Only few
      cells can migrate and differentiation towards oligodendrocyte lineage does not
      occur. Isolated A2B5+ cells from both glioblastomas and oligodendrogliomas showed
      similar genetic alterations as the whole tumour. Therefore, pilocytic
      astrocytomas contain slowly dividing oligodendrocyte-type2
      astrocyte/oligodendrocyte precursor cells in keeping with their benign behaviour
      whereas both glioblastomas and oligodendrogliomas contain neoplastic glial
      restricted precursor cells. In oligodendrogliomas, these cells are trapped in
      undifferentiated and proliferating state. The precursor cells properties present
      in gliomas give new insight into their histogenesis and open up new avenues for
      research in the field of gliomagenesis.

PMID- 16599949
TI  - PIK3CA mutations in oligodendroglial tumours.

PMID- 16599950
TI  - Embolic atrial myxoma with neoplastic aneurysm formation and haemorrhage: a
      diagnostic challenge.

PMID- 16599951
TI  - Mixed glioneuronal tumour of the fourth ventricle with prominent rosette
      formation.
AB  - We describe three unusual tumours characterized by a mixture of glial and
      neuronal differentiation, involvement of the posterior fossa and formation of
      rosettes. Mixed glial-neuronal tumours of the posterior fossa are rare and poorly
      described neoplasms. However, several distinctive entities have appeared in the
      literature over recent years under a variety of different names. Our cases
      demonstrate the morphological features of the 'rosette-forming glioneuronal
      tumour of the fourth ventricle', a recently identified tumour characterised by
      its unique location, neurocytic pseudo-rosette formation and the presence of a
      low grade astrocytoma component. The long term prognosis of these tumours remains
      unclear. However, the clinical data available including the cases presented here,
      along with the histological features, suggest that these are low grade tumours
      with a good prognosis after surgical resection.

PMID- 16599954
TI  - Studying phenotypic evolution using multivariate quantitative genetics.
AB  - Quantitative genetics provides a powerful framework for studying phenotypic
      evolution and the evolution of adaptive genetic variation. Central to the
      approach is G, the matrix of additive genetic variances and covariances. G
      summarizes the genetic basis of the traits and can be used to predict the
      phenotypic response to multivariate selection or to drift. Recent analytical and
      computational advances have improved both the power and the accessibility of the
      necessary multivariate statistics. It is now possible to study the relationships
      between G and other evolutionary parameters, such as those describing the
      mutational input, the shape and orientation of the adaptive landscape, and the
      phenotypic divergence among populations. At the same time, we are moving towards
      a greater understanding of how the genetic variation summarized by G evolves.
      Computer simulations of the evolution of G, innovations in matrix comparison
      methods, and rapid development of powerful molecular genetic tools have all
      opened the way for dissecting the interaction between allelic variation and
      evolutionary process. Here I discuss some current uses of G, problems with the
      application of these approaches, and identify avenues for future research.

PMID- 16599955
TI  - Patterns, sources and ecological implications of clonal diversity in apomictic
      Ranunculus carpaticola (Ranunculus auricomus complex, Ranunculaceae).
AB  - Sources and implications of genetic diversity in agamic complexes are still under
      debate. Population studies (amplified fragment length polymorphisms,
      microsatellites) and karyological methods (Feulgen DNA image densitometry and
      flow cytometry) were employed for characterization of genetic diversity and
      ploidy levels of 10 populations of Ranunculus carpaticola in central Slovakia.
      Whereas two diploid populations showed high levels of genetic diversity, as
      expected for sexual reproduction, eight populations are hexaploid and harbour
      lower degrees of genotypic variation, but maintain high levels of heterozygosity
      at many loci, as is typical for apomicts. Polyploid populations consist either of
      a single AFLP genotype or of one dominant and a few deviating genotypes.
      genotype/genodive and character incompatibility analyses suggest that genotypic
      variation within apomictic populations is caused by mutations, but in one
      population probably also by recombination. This local facultative sexuality may
      have a great impact on regional genotypic diversity. Two microsatellite loci
      discriminated genotypes separated by the accumulation of few mutations ('clone
      mates') within each AFLP clone. Genetic diversity is partitioned mainly among
      apomictic populations and is not geographically structured, which may be due to
      facultative sexuality and/or multiple colonizations of sites by different clones.
      Habitat differentiation and a tendency to inhabit artificial meadows is more
      pronounced in apomictic than in sexual populations. We hypothesize that
      maintenance of genetic diversity and superior colonizing abilities of apomicts in
      temporally and spatially heterogeneous environments are important for their
      distributional success.

PMID- 16599956
TI  - Effect of disturbances on the genetic diversity of an old-forest associated
      lichen.
AB  - Lichens associated with old forest are commonly assumed to be negatively affected
      by tree logging or natural disturbances. However, in this study performed in a
      spruce-dominated sylvopastoral landscape in the Swiss Jura Mountains, we found
      that genetic diversity of the epiphytic old-forest lichen Lobaria pulmonaria
      depends on the type of disturbance. We collected 923 thalli from 41 sampling
      plots of 1 ha corresponding to the categories stand-replacing disturbance
      (burnt), intensive logging (logged) and uneven-aged forestry (uneven-aged), and
      analysed the thalli at six mycobiont-specific microsatellite loci. We found
      evidence for multiple independent immigrations into demes located in burnt and
      logged areas. Using spatial autocorrelation methods, the spatial scale of the
      genetic structure caused by the clonal and recombinant component of genetic
      variation was determined. Spatial autocorrelation of genotype diversity was
      strong at short distances up to 50 m in logged demes, up to 100 m in uneven-aged
      demes, with the strongest autocorrelation up to 150 m for burnt demes. The
      spatial autocorrelation was predominantly attributed to clonal dispersal of
      vegetative propagules. After accounting for the clonal component, we did not find
      significant spatial autocorrelation in gene diversity. This pattern may indicate
      low dispersal ranges of clonal propagules, but random dispersal of sexual
      ascospores. Genetic diversity was highest in logged demes, and lowest in burnt
      demes. Our results suggest that genetic diversity of epiphytic lichen demes may
      not necessarily be impacted by stand-level disturbances for extended time
      periods.

PMID- 16599957
TI  - A comparison of variability and population structure for major histocompatibility
      complex and microsatellite loci in California coastal steelhead (Oncorhynchus
      mykiss Walbaum).
AB  - The major histocompatibility complex (MHC) contains genes integral to immune
      response in vertebrates. MHC genes have been shown to be under selection in a
      number of vertebrate taxa, making them intriguing for population genetic studies.
      We have conducted a survey of genetic variation in an MHC class II gene for
      steelhead trout from 24 sites in coastal California and compared this variation
      to that observed at 16 presumably neutral microsatellite loci. A high amount of
      allelic variation was observed at the MHC when compared to previously published
      studies on other Pacific salmonids. Elevated nonsynonymous substitutions,
      relative to synonymous substitutions, were detected at the MHC gene, indicating
      the signature of historical balancing selection. The MHC data were tested for
      correlations to and deviations from the patterns found with the microsatellite
      data. Estimates of allelic richness for the MHC gene and for the microsatellites
      were positively correlated, as were estimates of population differentiation
      (F(ST)). An analysis for F(ST) outliers indicates that the MHC locus has an
      elevated F(ST) relative to the neutral expectation, although a significant result
      was found for only one particular geographical subgroup. Relatively uniform
      allele frequency distributions were detected in four populations, although this
      finding may be partially due to recent population bottlenecks. These results
      indicate that, at the scale studied here, drift and migration play a major role
      in the observed geographical variability of MHC genes in steelhead, and that
      contemporary selection is relatively weak and difficult to detect.

PMID- 16599958
TI  - Y-chromosome analysis confirms highly sex-biased dispersal and suggests a low
      male effective population size in bonobos (Pan paniscus).
AB  - Dispersal is a rare event that is difficult to observe in slowly maturing, long
      lived wild animal species such as the bonobo. In this study we used sex-linked
      (mitochondrial DNA sequence and Y-chromosome microsatellite) markers from the
      same set of individuals to estimate the magnitude of difference in effective
      dispersal between the sexes and to investigate the long-term demographic history
      of bonobos. We sampled 34 males from four distinct geographical areas across the
      bonobo distribution range. As predicted for a female-dispersing species, we found
      much higher levels of differentiation among local bonobo populations based upon Y
      chromosomal than mtDNA genetic variation. Specifically, almost all of the Y
      chromosomal variation distinguished populations, while nearly all of the mtDNA
      variation was shared between populations. Furthermore, genetic distance
      correlated with geographical distance for mtDNA but not for the Y chromosome.
      Female bonobos have a much higher migration rate and/or effective population size
      as compared to males, and the estimate for the mitochondrial TMRCA (time to most
      recent common ancestor) was approximately 10 times greater than the estimate for
      the Y chromosome (410,000 vs. 40,000-45,000). For humans the difference is merely
      a factor of two, suggesting a more stable demographic history in bonobos in
      comparison to humans.

PMID- 16599959
TI  - Panmixia: an example from Dawson's burrowing bee (Amegilla dawsoni) (Hymenoptera:
      Anthophorini).
AB  - Dawson's burrowing bee is a large, fast-flying solitary nesting bee endemic to
      the arid zone of Western Australia. In this study the population structure of the
      species was examined with molecular markers. Using eight microsatellite loci, we
      genotyped 531 adult female bees collected from 13 populations of Dawson's
      burrowing bee, Amegilla dawsoni, across the species range. The mean number of
      alleles per locus ranged from 4 to 38 and expected heterozygosity was uniformly
      high with a mean of 0.602. Pairwise comparisons of F(ST) among all 13 populations
      ranged from 0.0071 to 0.0122 with only one significant estimate and an overall
      F(ST) of 0.001. The entire sample collection was in Hardy-Weinberg equilibrium
      and there was no evidence of inbreeding with a mean F(IS) of 0.010. The mating
      and nesting behaviour of this bee suggests that gene flow would be limited by
      monandry and the fact that almost 90% of females mate immediately on emergence.
      Nevertheless there is obviously sufficient gene flow to maintain panmixia, and we
      suggest that this results from infrequent and unreliable rainfall in the species
      range, which causes the bees to congregate at limited food resources, allowing a
      small number of unmated females from one emergence site to come into contact with
      males from another population. In addition, when drought eliminates food
      resources near an emergence site, the whole population may move elsewhere,
      increasing gene flow across the species range.

PMID- 16599960
TI  - Population genetic structure of Japanese wild soybean (Glycine soja) based on
      microsatellite variation.
AB  - The research objectives were to determine aspects of the population dynamics
      relevant to effective monitoring of gene flow in the soybean crop complex in
      Japan. Using 20 microsatellite primers, 616 individuals from 77 wild soybean
      (Glycine soja) populations were analysed. All samples were of small seed size (<
      0.03 g), were directly collected in the field and came from all parts of Japan
      where wild soybeans grow, except Hokkaido. Japanese wild soybean showed
      significant reduction in observed heterozygosity, low outcrossing rate (mean
      3.4%) and strong genetic differentiation among populations. However, the
      individual assignment test revealed evidence of rare long-distance seed dispersal
      (> 10 km) events among populations, and spatial autocorrelation analysis revealed
      that populations within a radius of 100 km showed a close genetic relationship to
      one another. When analysis of graphical ordination was applied to compare the
      microsatellite variation of wild soybean with that of 53 widely grown Japanese
      varieties of cultivated soybean (Glycine max), the primary factor of genetic
      differentiation was based on differences between wild and cultivated soybeans and
      the secondary factor was geographical differentiation of wild soybean
      populations. Admixture analysis revealed that 6.8% of individuals appear to show
      introgression from cultivated soybeans. These results indicated that population
      genetic structure of Japanese wild soybean is (i) strongly affected by the
      founder effect due to seed dispersal and inbreeding strategy, (ii) generally well
      differentiated from cultivated soybean, but (iii) introgression from cultivated
      soybean occurs. The implications of the results for the release of transgenic
      soybeans where wild soybeans grow are discussed.

PMID- 16599961
TI  - History vs. current demography: explaining the genetic population structure of
      the common frog (Rana temporaria).
AB  - The amount of genetic variability at neutral marker loci is expected to decrease,
      and the degree of genetic differentiation among populations to increase, as a
      negative function of effective population size. We assessed the patterns of
      genetic variability and differentiation at seven microsatellite loci in the
      common frog (Rana temporaria) in a hierarchical sampling scheme involving three
      regions (208-885 km apart), three subregions within regions and nine populations
      (5-20 km apart) within subregions, and related the variability and
      differentiation estimates to variation in local population size estimates.
      Genetic variability within local populations decreased significantly with
      increasing latitude, as well as with decreasing population size and regional site
      occupancy (proportion of censured localities occupied). The positive relationship
      between population size and genetic variability estimates was evident also when
      the effect of latitude (cf. colonization history) was accounted for. Significant
      genetic differentiation was found at all hierarchical levels, and the degree of
      population differentiation tended to increase with increasing latitude. Isolation
      by distance was evident especially at the regional sampling level, and its
      strength increased significantly towards the north in concordance with decreasing
      census and marker-based neighbourhood size estimates. These results are in line
      with the conjecture that the influence of current demographic factors can
      override the influence of historical factors on species population genetic
      structure. Further, the observed reductions in genetic variability and increased
      degree of population differentiation towards the north are in line with
      theoretical and empirical treatments suggesting that effective population sizes
      decline towards the periphery of a species' range.

PMID- 16599962
TI  - Estimating population structure under nonequilibrium conditions in a conservation
      context: continent-wide population genetics of the giant Amazon river turtle,
      Podocnemis expansa (Chelonia; Podocnemididae).
AB  - Giant Amazon river turtles, Podocnemis expansa, are indigenous to the Amazon,
      Orinoco, and Essequibo River basins, and are distributed across nearly the entire
      width of the South American continent. Although once common, their large size,
      high fecundity, and gregarious nesting, made P. expansa especially vulnerable to
      over-harvesting for eggs and meat. Populations have been severely reduced or
      extirpated in many areas throughout its range, and the species is now regulated
      under Appendix II of the Convention on International Trade in Endangered Species.
      Here, we analyse data from mitochondrial DNA sequence and multiple nuclear
      microsatellite markers with an array of complementary analytical methods. Results
      show that concordance from multiple data sets and analyses can provide a strong
      signal of population genetic structure that can be used to guide management. The
      general lack of phylogeographic structure but large differences in allele and
      haplotype frequencies among river basins is consistent with fragmented
      populations and female natal-river homing. Overall, the DNA data show that P.
      expansa populations lack a long history of genetic differentiation, but that each
      major tributary currently forms a semi-isolated reproductive population and
      should be managed accordingly.

PMID- 16599963
TI  - Mitochondrial DNA reveals a strong phylogeographic structure in the badger across
      Eurasia.
AB  - The badger, Meles meles, is a widely distributed mustelid in Eurasia and shows
      large geographic variability in morphological characters whose evolutionary
      significance is unclear and needs to be contrasted with molecular data. We
      sequenced 512 bp of the mitochondrial DNA control region in 115 Eurasian badgers
      from 21 countries in order to test for the existence of structuring in their
      phylogeography, to describe the genetic relationships among their populations
      across its widespread geographic range, and to infer demographic and
      biogeographic processes. We found that the Eurasian badger is divided into four
      groups regarding their mitochondrial DNA: Europe, Southwest Asia, North and East
      Asia, and Japan. This result suggests that the separation of badgers into
      phylogeographic groups was influenced by cold Pleistocene glacial stages and
      permafrost boundaries in Eurasia, and by geographic barriers, such as mountains
      and deserts. Genetic variation within phylogeographic groups based on distances
      assuming the Tamura-Nei model with rate heterogeneity and invariable sites (d(T
      N) range: 3.3-4.2) was much lower than among them (d(T-N) range: 10.7-38.0), and
      80% of the variation could be attributed to differences among regions. Spatial
      analysis of molecular variance (samova), median-joining network, and Mantel test
      did not detect genetic structuring within any of the phylogeographic groups with
      the exception of Europe, where 50% of variation was explained by differences
      among groups of populations. Our data suggest that the European, Southwest Asian,
      and North and East Asian badgers evolved separately since the end of Pliocene, at
      the beginnings of glacial ages, whereas Japanese badgers separated from
      continental Asian badgers during the middle Pleistocene. Endangered badgers from
      Crete Island, classified as Meles meles arcalus subspecies, were closely related
      to badgers from Southwest Asia. We also detected sudden demographic growth in
      European and Southwest Asian badgers that occurred during the Middle Pleistocene.

PMID- 16599964
TI  - Molecular ecology of zebra mussel invasions.
AB  - The invasion of the zebra mussel, Dreissena polymorpha, into North American
      waters has resulted in profound ecological disturbances and large monetary
      losses. This study examined the invasion history and patterns of genetic
      diversity among endemic and invading populations of zebra mussels using DNA
      sequences from the mitochondrial cytochrome oxidase I (COI) gene. Patterns of
      haplotype frequency indicate that all invasive populations of zebra mussels from
      North America and Europe originated from the Ponto-Caspian Sea region. The
      distribution of haplotypes was consistent with invasive populations arising from
      the Black Sea drainage, but could not exclude the possibility of an origin from
      the Caspian Sea drainage. Similar haplotype frequencies among North American
      populations of D. polymorpha suggest colonization by a single founding
      population. There was no evidence of invasive populations arising from tectonic
      lakes in Turkey, while lakes in Greece and Macedonia contained only Dreissena
      stankovici. Populations in Turkey might be members of a sibling species complex
      of D. polymorpha. Ponto-Caspian derived populations of D. polymorpha (theta =
      0.0011) and Dreissena bugensis (one haplotype) exhibited low levels of genetic
      diversity at the COI gene, perhaps as a result of repeated population
      bottlenecks. In contrast, geographically isolated tectonic lake populations
      exhibited relatively high levels of genetic diversity (theta = 0.0032 to 0.0134).
      It is possible that the fluctuating environment of the Ponto-Caspian basin
      facilitated the colonizing habit of invasive populations of D. polymorpha and D.
      bugensis. Our findings were concordant with the general trend of destructive
      freshwater invaders in the Great Lakes arising from the Ponto-Caspian Sea basin.

PMID- 16599965
TI  - Phylogeography and systematics of zebra mussels and related species.
AB  - The genus Dreissena includes two widespread and aggressive aquatic invaders, the
      zebra mussel, Dreissena polymorpha, and the quagga mussel, Dreissena bugensis.
      This genus evolved in the Ponto-Caspian Sea basin, characterized by dynamic
      instability over multiple timescales and a unique evolutionary environment that
      may predispose to invasiveness. The objectives of this study were to gain
      insights into the demographic history of Dreissena species in their endemic
      range, to reconstruct intraspecific phylogeographic relationships among
      populations, and to clarify systematics of the genus, using DNA sequences from
      the mitochondrial cytochrome oxidase I (COI) gene. We found four deeply diverged
      clades within this genus, with a basal split that approximately coincided with
      the Cretaceous-Tertiary boundary. Divergence events within the four base clades
      were much more recent, corresponding to geographically disjunct sets of
      populations, which might represent species complexes. Across all taxa,
      populations of Dreissena shared a common pattern of genetic signatures indicating
      historical population bottlenecks and expansions. Haplotype diversity was
      relatively low in Ponto-Caspian drainages relative to more stable tectonic lakes
      in Greece, Macedonia, and Turkey. The phylogeographic and demographic patterns in
      the endemic range of Dreissena might have resulted from vicariance events,
      habitat instability, and the high fecundity and passive dispersal of these
      organisms.

PMID- 16599966
TI  - The determinant role of temporary proglacial drainages on the genetic structure
      of fishes.
AB  - Phylogeographic studies have shed light on Pleistocene glaciations as a key
      factor in shaping present-day genetic structure of many organisms. In formerly
      glaciated regions, the combined action of several factors such as refuges origin,
      physiological capacities and demographic parameters have contributed importantly
      to this process but specifically for each species. Therefore, a fine-scale
      genetic structure is not expected to be similar for different species, unless it
      has been modulated by the action of a strong environmental pressure. The aim of
      this study is to investigate the effects of postglacial environment on the
      genetic structure of fishes. To achieve this objective, three fish species
      (northern pike, lake whitefish and yellow perch) commonly found in sympatry in
      Laurentian Shield lakes but displaying different ecological and physiological
      characteristics were analysed. The comparison of these unrelated species was
      performed to identify the factors determining the organization of their genetic
      structure. Populations of all species mostly originated from the Mississippian
      refuge. Low genetic differentiation was observed among populations but
      significant structures were detected for the three species. Despite marked
      differences among species, these structures presented common characteristics: a
      lack of congruence with drainage and a longitudinal organization. This suggested
      that the dispersion of species occurred independently, leading to a species
      specific structure. However, the settling of populations appeared to be mediated
      by a dynamic system of proglacial meltwater streams associated to the glacial
      Lake Ojibway-Barlow, providing such similarities among species.

PMID- 16599967
TI  - Correlates of genetic differentiation and isolation by distance in 17 congeneric
      Silene species.
AB  - The contemporary pattern of intraspecific genetic variation can indicate the
      relative role of gene flow and local differentiation in shaping the evolutionary
      history and future trajectory of a species. To assess the recent influence of
      contrasting life history and demographic characteristics on genetic structure
      within a group of closely related species, patterns of genetic differentiation
      (F(ST) and related statistics) and isolation by distance (IBD) were compared
      among 17 congeneric herbaceous plant species. Data came from 35 published studies
      of 16 species, and a previously unpublished analysis of chloroplast genetic
      variation in the rare endemic Silene rotundifolia. Among-population genetic
      variance was most strongly influenced by the type of genetic marker used;
      cytoplasmic markers showed larger values than allozyme and anonymous nuclear
      markers. Other independently significant factors were geographical range size
      and, for allozyme studies, reproductive system; in particular, endemism and
      hermaphroditism were associated with higher among-population genetic variance,
      whereas large native geographical range and dioecy were associated with lower
      among-population variance. Over equivalent spatial scales, dioecious populations
      also showed weaker IBD than hermaphrodites, perhaps because increased population
      transience and/or variance in the spatial pattern of gene flow are more closely
      associated with dioecy in this genus. Invasive populations had both highly
      variable among-population genetic variance, and no evidence for IBD, consistent
      with nonequilibrium conditions. Other analysed factors including predominant
      pollinator had no discernable influence on genetic structure or patterns of IBD.
      In general, this comparative approach appears to be valuable for synthesizing the
      complementary information provided by F-statistics and IBD, and for indicating
      the relative importance of particular biological factors in shaping genetic
      variation within different species of a closely related plant group.

PMID- 16599968
TI  - Biogeographic history of an Australian freshwater shrimp, Paratya australiensis
      (Atyidae): the role life history transition in phylogeographic diversification.
AB  - The widespread distribution of the freshwater shrimp Paratya australiensis in
      eastern Australia suggests that populations of this species have been connected
      in the past. Amphidromy is ancestral in these shrimps, although many extant
      populations are known to be restricted to freshwater habitats. In this study, we
      used a fragment of the cytochrome c oxidase I mitochondrial DNA (mtDNA) gene to
      examine diversity within P. australiensis and to assess the relative importance
      of amphidromy in its evolutionary history. We hypothesized that if transitions
      from an amphidromous to a freshwater life history were important, then we would
      find a number of divergent lineages restricted to single or groups of nearby
      drainages. Alternatively, if amphidromy was maintained within the species
      historically, we expected to find lineages distributed over many drainages. We
      assumed that the only way for divergence to occur within amphidromous lineages
      was if dispersal was limited to between nearby estuaries, which, during arid
      periods in the earth's history, became isolated from one another. We found nine
      highly divergent mtDNA lineages, estimated to have diverged from one another in
      the late Miocene/early Pliocene, when the climate was more arid than at present.
      Despite this, the geographic distribution of lineages and haplotypes within
      lineages did not support the notion of a stepping-stone model of dispersal
      between estuaries. We conclude that the extensive divergence has most likely
      arisen through a number of independent amphidromy-freshwater life history
      transitions, rather than via historical isolation of amphidromy populations. We
      also found evidence for extensive movement between coastal and inland drainages,
      supporting the notion that secondary contact between lineages may have occurred
      as a result of drainage rearrangements. Finally, our data indicate that P.
      australiensis is likely a complex of cryptic species, some of which are widely
      distributed, and others geographically restricted.

PMID- 16599969
TI  - Genetic structure of sibling butterfly species affected by Wolbachia infection
      sweep: evolutionary and biogeographical implications.
AB  - It was recently recognized that in Japan, the common yellow butterfly, Eurema
      hecabe, consists of two sibling species, which have been unnamed yet and
      tentatively called yellow (Y) type and brown (B) type. We investigated the
      diversity of nuclear and mitochondrial genes in Japanese populations of Y type
      and B type of E. hecabe. The phylogeny based on nuclear genes agreed with the
      distinction between Y type and B type, which had been also supported by a wide
      array of biological data. However, the phylogeny based on mitochondrial genes did
      not reflect the distinction. PCR survey of Wolbachia revealed that B-type
      populations were all infected while Y-type populations contained both infected
      and uninfected individuals. A single genotype of Wolbachia, which was inferred to
      be a CI-inducing strain from their wsp gene sequence, was prevalent in these
      populations. Notably, the mitochondrial phylogeny was in perfect agreement with
      the pattern of Wolbachia infection, suggesting that the Wolbachia infection had
      affected the mitochondrial genetic structure of the host insects. Probably, the
      Wolbachia strain and the associated mitochondrial genomes have been occasionally
      introduced from B-type populations to Y-type populations through migration and
      subsequent interspecific hybridization, and CI-driven population sweep has been
      spreading the Wolbachia strain and the particular mitochondrial haplotypes, which
      originated from B-type populations, into Y-type populations. On the basis of
      these results together with the geological and biogeographical knowledge of the
      Japanese Archipelago, we proposed an evolutionary hypothesis on the invasion and
      spread of Wolbachia infection in B-type and Y-type of E. hecabe.

PMID- 16599970
TI  - Microsatellite analysis of the phylogeography, Pleistocene history and secondary
      contact hypotheses for the killifish, Fundulus heteroclitus.
AB  - The mummichog, Fundulus heteroclitus, exhibits extensive latitudinal clinal
      variation in a number of physiological and biochemical traits, coupled with
      phylogeographical patterns at mitochondrial and nuclear DNA loci that suggest a
      complicated history of spatially variable selection and secondary intergradation.
      This species continues to serve as a model for understanding local and regional
      adaptation to variable environments. Resolving the influences of historical
      processes on the distribution of genetic variation within and among extant
      populations of F. heteroclitus is crucial to a better understanding of how
      populations evolve in the context of contemporary environments. In this study, we
      analysed geographical patterns of genetic variation at eight microsatellite loci
      among 15 populations of F. heteroclitus distributed throughout the North American
      range of the species from Nova Scotia to Georgia. Genetic variation in Northern
      populations was lower than in Southern populations and was strongly correlated
      with latitude throughout the species range. The most common Northern alleles at
      all eight loci exhibited concordant latitudinal clinal patterns, and the
      existence of an abrupt transition zone in allele frequencies between Northern and
      Southern populations was similar to that observed for mitochondrial DNA and
      allozyme loci. A significant pattern of isolation by distance was observed both
      within and between northern and southern regions. This pattern was unexpected,
      particularly for northern populations, given the recent colonization history of
      post-Pleistocene habitats, and was inconsistent with either a recent northward
      population expansion or a geographically restricted northern Pleistocene
      refugium. The data provided no evidence for recent population bottlenecks, and
      estimates of historical effective population sizes suggest that post-Pleistocene
      populations have been large throughout the species distribution. These results
      suggest that F. heteroclitus was broadly distributed throughout most of its
      current range during the last glacial event and that the abrupt transition in
      allele frequencies that separate Northern and Southern populations may reflect
      regional disequilibrium conditions associated with the post-Pleistocene
      colonization history of habitats in that region.

PMID- 16599971
TI  - Late Quaternary climate change and spatial genetic structure in the shrub Banksia
      hookeriana.
AB  - Spatial genetic variation within species is influenced by both contemporary and
      historical factors. We attempted to assess the impact of increased aridity and
      lower temperatures associated with the last glacial maximum on possible refugia
      and the structuring of genetic variation in Banksia hookeriana, a shrub species
      restricted to deep sands on the Eneabba sandplain and adjacent Gingin
      Scarp/Dandaragan Plateau, centred 300 km north of Perth, Western Australia. We
      used optically stimulated luminescence (OSL) dating to estimate the last time
      these sands were mobile, as well as amplified fragment length polymorphisms
      (AFLP) to infer spatial patterns and the phylogeographical history of genetic
      variation among 15 populations of B. hookeriana. While genetic variation at the
      species level was high, with 96.6% of 238 AFLP markers polymorphic, average
      within population gene diversity was low (H(pop) = 0.16). Of the total genetic
      variation, an analysis of molecular variance (amova) partitioned 70% within
      populations, 24% among populations within substrate and 6% between substrates.
      There was an isolation-by-distance effect among populations within the same
      substrate, but not across substrates, and ordination highlighted genetic
      differentiation between the sandplain and scarp/plateau populations. A neighbour
      joining tree identified the sandplain populations as a distinct clade, with the
      exception of the most northern sandplain population, which clustered with two
      northern and eastern plateau populations. The most southern plateau populations
      formed a clade sister to the sandplain clade. OSL dating of sand at six extant
      populations suggested that dunes were last mobile 15,000-35,000 years ago, with
      no clear difference in the ages of sandplain and plateau dunes. These data are
      consistent with a historical scenario of (re)colonization from isolated refugia
      of smaller populations either within the patchily vegetated sandplain and/or
      refugia at the northern, eastern and southern sandplain/scarp margins following
      postglacial climate amelioration and dune stabilization. Historic interpretations
      were confounded by the possible effects of long-distance dispersal, natural
      selection by substrate, and weak and/or ancient introgression with the sister
      species, Banksia prionotes.

PMID- 16599972
TI  - Kin distribution of amphibian larvae in the wild.
AB  - According to kin selection theory, the location of an individual with respect to
      its relatives can have important ramifications for its fitness. Perhaps more than
      any other vertebrate group, anuran amphibian larvae have been the subject of many
      experiments on this topic. Some anuran species have been shown in the laboratory
      to recognize and associate with their siblings and half-siblings. However, due to
      the difficulty of identifying sibships, no kinship studies with anuran larvae
      have been conducted in the wild. Here, we use microsatellite analysis to show
      that wood frog (Rana sylvatica) tadpoles were nonrandomly distributed in two
      ponds with respect to their relatives. In one pond, the tadpoles were
      significantly clumped with their siblings or half-siblings as expected from other
      published laboratory studies on this species. However, in another pond, the
      tadpoles were significantly nonrandomly dispersed from their siblings or half
      siblings. This is the first example of kin repulsion of nonreproductive animals
      in the wild and the first time a species has been shown to display both
      aggregation and repulsion under different circumstances. These results suggest
      that kin distribution is context dependent and demonstrate the importance of
      testing kin selection hypotheses under natural conditions.

PMID- 16599973
TI  - Male parentage in army ants.
AB  - In most social insects workers do not mate, but have retained the ability to
      produce haploid eggs that can develop into viable male offspring. Under what
      circumstances this reproductive potential is realized and how the ensuing worker
      queen conflict over male production is resolved, is an area of active research in
      insect sociobiology. Here we present microsatellite data for 176 males from eight
      colonies of the African army ant Dorylus (Anomma) molestus. Comparison with
      worker genotypes and inferred queen genotypes from the same colonies show that
      workers do not or at best very rarely reproduce in the presence of the queen.
      Queens of D. (A.) molestus are known to be highly multiply mated. This implies
      that workers are on average more closely related to queen sons than to other
      workers' sons, so that our results are consistent with predictions from inclusive
      fitness theory. It remains unknown, however, whether worker sterility is
      maintained by active worker policing or by self-restraint.

PMID- 16599974
TI  - Genetic variation in MHC class II expression and interactions with MHC sequence
      polymorphism in three-spined sticklebacks.
AB  - Genes of the major histocompatibility complex (MHC) have been studied for several
      decades because of their pronounced allelic polymorphism. Structural allelic
      polymorphism is, however, not the only source of variability subjected to natural
      selection. Genetic variation may also exist in gene expression patterns. Here, we
      show that in a natural population of three-spined sticklebacks (Gasterosteus
      aculeatus) the expression of MHC class IIB genes was positively correlated with
      parasite load, which indicates increased immune activation of the MHC when
      infections are frequent. To experimentally study MHC expression, we used
      laboratory-bred sticklebacks that were exposed to three naturally occurring
      species of parasite. We found strong differences in MHC class IIB expression
      patterns among fish families, which were consistent over two generations, thus
      demonstrating a genetic component. The average number of MHC class IIB sequence
      variants within families was negatively correlated to the MHC expression level
      suggesting compensatory up-regulation in fish with a low (i.e. suboptimal) MHC
      sequence variability. The observed differences among families and the negative
      correlation with individual sequence diversity imply that MHC expression is
      evolutionary relevant for the onset and control of the immune response in natural
      populations.

PMID- 16599975
TI  - Seasonal changes in pollinator activity influence pollen dispersal and seed
      production of the alpine shrub Rhododendron aureum (Ericaceae).
AB  - In alpine ecosystems, microscale variation in snowmelt timing often causes
      different flowering phenology of the same plant species and seasonal changes in
      pollinator activity. We compared the variations in insect visitation, pollen
      dispersal, mating patterns, and sexual reproduction of Rhododendron aureum early
      and late in the flowering season using five microsatellites. Insects visiting the
      flowers were rare early in the flowering season (mid-June), when major
      pollinators were bumblebee queens and flies. In contrast, frequent visitations by
      bumblebee workers were observed late in the season (late July). Two-generation
      analysis of pollen pool structure demonstrated that quality of pollen-mediated
      gene flow was more diverse late in the season in parallel with the high
      pollinator activity. The effective number of pollen donors per fruit (N(ep))
      increased late in the season (N(ep) = 2.2-2.7 early, 3.4-4.4 late). However, both
      the outcrossing rate (t(m)) and seed-set ratio per fruit were smaller late in the
      season (t(m) = 0.89 and 0.71, seed-set ratio = 0.52 and 0.18, early and late in
      the season, respectively). In addition, biparental inbreeding occurred only late
      in the season. We conclude that R. aureum shows contrasting patterns of pollen
      movement and seed production between early and late season: in early season, seed
      production can be high but genetically less diverse and, during late season, be
      reduced, possibly due to higher inbreeding and inbreeding depression, but have
      greater genetic diversity. Thus, more pollinator activity does not always mean
      more pollen movement.

PMID- 16599976
TI  - Fitness of hybrids between rapeseed (Brassica napus) and wild Brassica rapa in
      natural habitats.
AB  - Fitness of hybrids between genetically modified (GM) crops and wild relatives
      influences the likelihood of ecological harm. We measured fitness components in
      spontaneous (non-GM) rapeseed x Brassica rapa hybrids in natural populations. The
      F1 hybrids yielded 46.9% seed output of B. rapa, were 16.9% as effective as males
      on B. rapa and exhibited increased self-pollination. Assuming 100% GM rapeseed
      cultivation, we conservatively predict < 7000 second-generation transgenic
      hybrids annually in the United Kingdom (i.e. approximately 20% of F1 hybrids).
      Conversely, whilst reduced hybrid fitness improves feasibility of bio
      containment, stage projection matrices suggests broad scope for some transgenes
      to offset this effect by enhancing fitness.

PMID- 16599977
TI  - A reply to Engel et al.

PMID- 16599978
TI  - Cryptic population structuring in Scandinavian lynx: reply to Pamilo.
AB  - In a recent Commentary in this journal, Pamilo (2004) criticized our analysis of
      the spatial genetic structure of the Eurasian lynx in Scandinavia (Rueness et al.
      2003). The analyses uncovered a marked geographical differentiation along the
      Scandinavian peninsula with an apparent linear gradient in the north-south
      direction. We used computer simulations to check on the proposition that the
      observed geographical structure could have arisen by genetic drift and isolation
      by distance in the approximate 25 generations that have passed since the last
      bottleneck. Pamilo disapproved of our choice of population model and also how we
      compared the outcome of the simulations with data. As these issues should be of
      interest to a wider audience we discuss them in some detail.

PMID- 16599979
TI  - Mycobacterium avium ssp. paratuberculosis and its potential survival tactics.
AB  - Mycobacterium avium ssp. paratuberculosis (Map) is an important animal pathogen
      with a potential, but as yet unproven, role in human disease. This review briefly
      describes the characteristics of Map that distinguish it from other Mycobacterium
      spp., presenting new information arising from completion of the sequencing of the
      Map genome. It then focuses on the potential mechanisms Map might employ to
      survive and disseminate in the environment, including interaction with protozoa
      and insects, dormancy, biofilm formation and aerosolization.

PMID- 16599980
TI  - A gzip-based algorithm to identify bacterial families by 16S rRNA.
AB  - AIMS: Microbial family identification of 16S rDNA sequences by applying a
      strategy based on algorithms for data compression. METHODS AND RESULTS: Perl
      scripts were developed to analyse similarities in microbial sequences, based on a
      gzip data compression technique. For each bacterial family (n=196) a 16S rRNA
      reference file was constructed to compare new queries looking at compression
      performance. An online user-friendly bioinformatics tool was built up to
      attribute a bacterial family to a 16S rRNA sequence. It was successfully applied
      to recognize different bacterial families, including Legionellaceae, Bacillaceae,
      Enterobacteriaceae, Acetobacteriaceae and Rhizobiaceae. The percentage of
      positive identifications is higher than 95% for fragments over 450 bp.
      CONCLUSIONS: A new bioinformatics approach has been developed to assign a
      taxonomic classification to a 16SrDNA sequence. An online tool provides quick and
      easy sequence attribution. The general principle can be applied to other genes of
      taxonomic interest. SIGNIFICANCE AND IMPACT OF THE STUDY: Availability of simple
      bioinformatics tools can support the development of molecular-based analysis and
      classification of bacteria, especially for environmental or uncultured strains.

PMID- 16599981
TI  - The profiles of enterotoxin genes in Staphylococcus aureus from nasal carriers.
AB  - AIMS: To evaluate the occurrence of enterotoxin genes in Staphylococcus aureus
      recovered from nasal carriers. METHODS AND RESULTS: Eighty S. aureus strains were
      tested for the presence of 17 new enterotoxin genes using multiplex-PCR. Sixty
      one isolates were found to carry enterotoxin genes. The majority of the
      enterotoxigenic isolates carried enterotoxin gene cluster (egc) genes, namely
      seg, sei, sem, sen and seo. The egc type containing the seu gene was found in 19
      of the 47 isolates with egc-like genes. Interestingly, no seu-containing egc
      coexisted with sec and sel, as was the case for a considerable portion of the
      isolates carrying a seu-negative egc. The tst gene was detected in two isolates
      carrying sec and sel only and in eight isolates carrying seu, but not in the
      isolates containing the seu-negative egc type. CONCLUSIONS: The genes forming an
      egc were found to be predominant in S. aureus from nasal carriers. The
      coexistence of a seu-positive egc with tst in contrast to an egc lacking the seu
      gene apparently is not associated with the presence of tst and can reflect a
      difference between these gene groupings. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The egc types carried by the analysed isolates seem to have an influence on the
      distribution of other genes located on staphylococcal pathogenicity islands,
      which may modulate the repertoire of virulence factors carried by a single S.
      aureus strain.

PMID- 16599982
TI  - Effect of phosphate buffer concentration on the batch xylitol production by
      Candida guilliermondii.
AB  - AIMS: To evaluate the effect of phosphate buffer concentration on growth and
      xylitol production by Candida guilliermondii FTI 20037. METHODS AND RESULTS:
      Fermentations runs were carried out in batch mode employing semisynthetic medium
      supplemented with phosphate buffer at different concentrations (from 200 to 600
      mmol l(-1)). The xylitol yield (Y(P/S)) and volumetric productivity (Q(P)) were
      improved when the fermentation medium was supplemented with phosphate buffer at
      concentration of 600 mmol l(-1). Under this condition (Y(P/S)) and (Q(P)) values
      were 0.75 g g(-1) and 0.66 g l(-1) h(-1), respectively, whereas in the absence of
      the phosphate buffer these values decreased to 0.52 g g(-1) and 0.44 g l(-1)h(-1)
      respectively. CONCLUSIONS: The use of phosphate buffer at 600 mmol l(-1) promoted
      an easier pH control during shake flasks fermentation of C. guilliermondii. In
      addition the xylitol yield and productivity were significantly improved in
      response to the supplementation of potassium phosphate in the medium. The
      increase in these parameters could be related to both osmotic effect and pH
      control. SIGNIFICANCE AND IMPACT OF THE STUDY: This approach provided a method
      for improving the xylitol production from semisynthetic medium by C.
      guilliermondii, being possible their use as a simple strategy to achieve
      efficient fermentation processes employing complex medium such as lignocellulosic
      hydrolysates.

PMID- 16599983
TI  - Effects of water activity and temperature on the survival of Aspergillus
      carbonarius spores in vitro.
AB  - AIMS: To determine the effect of water activity (a(w)) and temperature on the
      survival of Aspergillus carbonarius spores. METHODS AND RESULTS: Spores of A.
      carbonarius were dried onto filter membranes. These filters were held at 1.0,
      0.9, 0.8, 0.6 and 0.4 a(w) and at 1, 15, 25 and 37 degrees C for up to 618 d. At
      intervals, spores were recovered from filters and assessed for viability by
      enumeration on dichloran rose bengal chloramphenicol agar. Survival and
      subsequent growth of spores was prolonged at low temperatures and at a(w) below
      0.6. Above 15 degrees C, 0.6-0.9 a(w) were often more deleterious than 1.0.
      However, at 1 degrees C and 1.0 a(w), spores lost viability more rapidly than at
      lower a(w). CONCLUSIONS: Increased incidence of black Aspergillus spp. in dry
      soils and from grapes in dry conditions may result partly from prolonged survival
      of spores. SIGNIFICANCE AND IMPACT OF THE STUDY: Delineating the direct effect of
      a(w) and temperature on survival of A. carbonarius spores may aid in
      understanding the incidence of this ochratoxin A-producing species in vineyard
      soils and on grapes.

PMID- 16599985
TI  - Fluorescence microscopy for studying the viability of micro-organisms in natural
      whey starters.
AB  - AIMS: The aim of this work was to study the viability and cultivability of
      microbial populations of different natural whey starters and to evaluate their
      resistance to thermal treatments (such as exposure to high or low temperatures).
      METHODS AND RESULTS: Twenty-three natural whey starters for Grana Padano cheese
      were investigated and subsequently pH measurement, plate count agar using Man
      Rogasa-Sharpe (MRS) pH 5.4 agar and whey agar medium (WAM) were performed using
      these samples. LIVE/DEAD BacLight bacterial viability kit was used. Total count
      and viability of all the 23 samples were high and similar to each other (CV 20%).
      However, the cultivable population was lower in terms of cfu ml(-1) and number of
      cells per millilitre than the viable fraction and highly variable, although its
      count value was higher in WAM than in MRS pH 5.4. The heating (60 degrees C for 5
      min and 54 degrees C for 1 h) and freezing (-20 and -80 degrees C) treatments
      affected the cultivability and viability of the microbial population.
      CONCLUSIONS: This study demonstrated the effectiveness of LIVE/DEAD BacLight
      bacterial viability kit, which has already been used to evaluate bacterial
      populations, in investigating microbial viability in a complex ecosystem such as
      a natural whey starter. SIGNIFICANCE AND IMPACT OF THE STUDY: The aim of this
      study was to quantify the presence of damaged nonviable bacterial cells in
      natural whey starters. The Thoma Glass is a useful method to obtain fluorescence
      microscopy counts to evaluate the technological performance of natural whey
      starters.

PMID- 16599984
TI  - Bacteriocin production, plasmid content and plasmid location of enterocin P
      structural gene in enterococci isolated from food sources.
AB  - AIMS: To characterize bacteriocin production, antimicrobial spectrum and plasmid
      content in bacteriocinogenic enterococci from foods. METHODS AND RESULTS:
      Bacteriocinogenic Enterococcus faecium (14 isolates) and Enterococcus faecalis
      (three isolates) showed two different patterns of bacteriocin production in
      liquid broth: exponential-phase and stationary-phase production. Bacteriocin
      concentrates from all enterococci were inactivated by trypsin, but seldom by heat
      (100-117 degrees C), extremes of pH (2.0 to 9.0) or reducing agents (such as
      dithiothreitol). All bacteriocin concentrates were active against Listeria
      innocua and Listeria monocytogenes, and most were also active against many Ent.
      faecalis and Ent. faecium isolates. Enterococci clustered in three main groups
      according to their plasmid content (which included plasmids from 2.0 to 53 kb).
      Several isolates from different foods showed almost identical plasmid profiles.
      The enterocin P structural gene (entP) was detected by hybridization on plasmids
      of c. 19, 26 and/or 35-38 kb. CONCLUSIONS: Enterococci from food show different
      patterns of bacteriocin production and different plasmid content in spite of
      carrying similar bacteriocin-encoding genes. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study provides information on the diversity of bacteriocinogenic
      enterococci from food sources carrying apparently similar enterocin genes.

PMID- 16599986
TI  - Synthesis of poly (3-hydroxybutyrate-co-3-hydroxyoctanoate) by a Sinorhizobium
      fredii strain.
AB  - AIMS: The potential of a Sinorhizobium fredii strain to produce a copolymer from
      glucose and sodium dodecanoate substrates was investigated. METHODS AND RESULTS:
      Using an orthogonal design in a flask-shaker culture system, the vital regulation
      conditions for copolymer synthesis were optimized. These optimal results were
      applied to further studies in a two-stage fed-batch fermentation with a 10-l
      fermentor. When the biomass approached 33.5 g l(-1) dry cells at 35 h, 7 mmol l(
      1) sodium dodecanoate was added into the broth to trigger the copolymer
      synthesis. After further culturing for 3 h, the copolymer product could be 17.14
      g l(-1). The molecular structure of the copolymer was determined to be a poly (3
      hydroxybutyrate-co-3-hydroxyoctanoate) [P (HB-HO)] by nuclear magnetic resonance.
      The content of HB and HO in P (HB-HO) was 79.2% (w/w) and 20.8% (w/w)
      respectively. The molecular weight of the P (HB-HO) was measured as 1.85 x 10(5)
      Da by a viscosity method. CONCLUSION: The results demonstrated that the S. fredii
      strain used could be a potential candidate for the industrial production of the
      copolymer. SIGNIFICANCE AND IMPACT OF THE STUDY: Some basic fermentation
      parameters were acquired through the fed-batch culturing experiments and they
      should be applicable in developing large-scale fermentation technologies for
      producing the P (HB-HO) copolymers.

PMID- 16599987
TI  - Evaluation of the methods for enumerating coliform bacteria from water samples
      using precise reference standards.
AB  - AIMS: To use BioBall cultures as a precise reference standard to evaluate methods
      for enumeration of Escherichia coli and other coliform bacteria in water samples.
      METHODS AND RESULTS: Eight methods were evaluated including membrane filtration,
      standard plate count (pour and spread plate methods), defined substrate
      technology methods (Colilert and Colisure), the most probable number method and
      the Petrifilm disposable plate method. Escherichia coli and Enterobacter
      aerogenes BioBall cultures containing 30 organisms each were used. All tests were
      performed using 10 replicates. The mean recovery of both bacteria varied with the
      different methods employed. CONCLUSIONS: The best and most consistent results
      were obtained with Petrifilm and the pour plate method. Other methods either
      yielded a low recovery or showed significantly high variability between
      replicates. SIGNIFICANCE AND IMPACT OF THE STUDY: The BioBall is a very suitable
      quality control tool for evaluating the efficiency of methods for bacterial
      enumeration in water samples.

PMID- 16599988
TI  - Inactivation of Salmonella Typhimurium and Listeria monocytogenes using high
      pressure treatments: destruction or sublethal stress?
AB  - AIMS: To investigate potential resuscitation of Listeria monocytogenes and
      Salmonella Typhimurium after high hydrostatic pressure treatments. METHODS AND
      RESULTS: Pressure treatments were applied at room temperature for 10 min on
      bacterial suspensions in buffers at pH 7 and 5.6. Total bacterial inactivation (8
      log(10) CFU ml(-1) of bacterial reduction) obtained by conventional plating was
      achieved regarding both micro-organisms. Treatments at 400 MPa in pH 5.6 and 600
      MPa in pH 7 for L. monocytogenes and at 350 MPa in pH 5.6 and 400 MPa in pH 7 for
      S. Typhimurium were required respectively. A 'direct viable count' method
      detected some viable cells in the apparently totally inactivated population.
      Resuscitation was observed for the two micro-organisms during storage (at 4 and
      20 degrees C) after almost all treatments. In the S. Typhimurium population, 600
      MPa, 10 min, was considered as the treatment achieving total destruction because
      no resuscitation was observed under these storage conditions. CONCLUSIONS: We
      suggest a delay before performing counts in treated samples in order to avoid the
      under-evaluation of surviving cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      resuscitation of pathogen bacteria after physical treatments like high
      hydrostatic pressure has to be considered from the food safety point of view.
      Further studies should be performed in food products to study this resuscitation
      phenomenon.

PMID- 16599989
TI  - Kinetic analysis of a trehalase-overexpressing strain grown on trehalose: a new
      tool for respiro-fermentative transition studies in Saccharomyces cerevisiae.
AB  - AIMS: The aim was to demonstrate the use of a trehalase-overexpressing
      Saccharomyces cerevisiae strain grown on trehalose as a valuable tool in the
      studies of respiro-fermentative transition at a reduced scale. METHODS AND
      RESULTS: A trehalase-overexpressing strain was cultivated in synthetic medium on
      trehalose under aerobic conditions. This strain grew at a maximum specific growth
      rate of 0.16 h(-1) and showed a pure oxidative metabolism. Glucose pulse
      experiments were carried out in this system in order to quantify the short-term
      Crabtree effect. These data were then compared with glucose pulse experiments
      carried out in the conventional way with the wild-type strain in glucose-limited
      chemostats. Glucose-pulse experiments in aerobic batch cultures grown on
      trehalose led to a metabolic respiro-fermentative transition similar to the one
      observed in glucose-limited chemostats. CONCLUSIONS: This cultivation system
      allowed us to quantitatively mimic at the flask scale the Crabtree effect
      observed in conventional chemostat studies. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study is of primary interest in S. cerevisiae studies in which: (i) the
      implementation of oxidative growth is required (as with studies of the Crabtree
      effect and heterologous protein production); (ii) small-scale culture systems are
      required (e.g. high-throughput mutant screening and isotopic labelling
      experiments).

PMID- 16599990
TI  - Effect of Lactobacillus isolates on the adhesion of pathogens to chicken
      intestinal mucus in vitro.
AB  - AIMS: The aims of this study were to investigate in vitro the effects of
      Lactobacillus isolates from a chicken on adhesion of pathogenic Salmonella and
      Escherichia coli to chicken intestinal mucus obtained from different intestinal
      regions. METHODS AND RESULTS: Bacteria were labelled by using methyl-1,2-[(3)H]
      thymidine. The bacterial adhesion was assessed by measuring the radioactivity of
      bacteria adhered to the mucus. The results showed that the abilities of
      Lactobacillus spp. to bind to the same intestinal mucus were higher than those of
      pathogenic Salmonella and E. coli. Pretreatment of intestinal mucus with
      Lactobacillus fermentum and Lactobacillus acidophilus, alone or in combination,
      reduced the adhesion of the tested pathogens, but the reductive extent of
      pathogenic adhesion by Lactobacillus spp. in combination was relatively high.
      CONCLUSIONS: The tested bacteria had different adhesions to mucus glycoproteins
      isolated from different intestinal regions of chicken. Lactobacillus acidophilus
      and Lact. fermentum in combination revealed a better ability to inhibit
      attachments of Salmonella and E. coli to chicken intestinal mucus than
      Lactobacillus sp. alone. SIGNIFICANCE AND IMPACT OF THE STUDY: A mixture of
      intestinal Lactobacillus spp. from a chicken may play a protective role in
      excluding pathogenic Salmonella and E. coli from the intestine of chicken.

PMID- 16599991
TI  - Identification of erythrobactin, a hydroxamate-type siderophore produced by
      Saccharopolyspora erythraea.
AB  - AIMS: To investigate the production of siderophores by Saccharopolyspora
      erythraea SGT2 and how this production is affected by the inoculum. METHODS AND
      RESULTS: When grown in a low-iron, chemically defined medium (CDM), the soil
      dwelling actinomycete S. erythraea secretes a substance that is reactive in the
      nonspecific chrome azurol S (CAS) assay. Importantly, the production of CAS
      reactive substance is highly reduced upon the addition of 0.925 micromol l(-1)
      iron to the cultures and has a peak of production in the late-log to early
      stationary growth phase. In addition, the culture supernatants tested were
      negative in the Arnow and Rioux assays but positive in the Csaky procedure.
      Interestingly, we also found evidence that the production of this CAS-reactive
      substance in CDM was highly reduced, when inoculated with cells that had been
      previously grown to late-stationary phase. Conversely, inocula derived from late
      log to early stationary cultures presented high levels of CAS activity.
      CONCLUSIONS: These results indicate that S. erythraea produces a hydroxamate-type
      siderophore that we have generically designated as erythrobactin. Additionally,
      the inocula growth stage plays a key role in siderophore production in S.
      erythraea. SIGNIFICANCE AND IMPACT OF THE STUDY: It is the first evidence for
      siderophore synthesis in S. erythraea and one of the first examples of non
      polyketide secondary metabolite production by this organism.

PMID- 16599992
TI  - An unusual reduction on the quinonoid ring of 5-amino-8-hydroxy-1,4
      naphthoquinone by Staphylococcus aureus.
AB  - AIMS: The objective of this study was to investigate the interactions between 5
      amino-8-hydroxy-1,4-naphthoquinone (ANQ) and Staphylococcus aureus. METHODS AND
      RESULTS: The compound ANQ display antimicrobial activity against S. aureus.
      During incubation with 50 microg ml(-1) of ANQ, an unusual reduction reaction
      takes place and leads to the isolation of 2,3-dihydro-5-amino-8-hydroxy-1,4
      naphthoquinone (ANQ-H(2)), fully characterized by means of (13)C-NMR and (1)H
      NMR, plus infrared, UV-visible and mass spectroscopy. Oxygen uptake by S. aureus
      cells was inhibited by ANQ, but in a significantly minor extent by ANQ-H(2).
      CONCLUSIONS: The ability of S. aureus to reduce the double bond at C2-C3 of the
      ANQ is a unusual behaviour for biological transformation of naphthoquinones.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This uncommon reaction may provide valuable
      understanding of the S. aureus regarding to the antimicrobial effect and the
      acquisition of resistance to naphthoquinones.

PMID- 16599993
TI  - Evaluation of a PCR detection method for Escherichia coli O157:H7/H- bovine
      faecal samples.
AB  - AIMS: Combinations of PCR primer sets were evaluated to establish a multiplex PCR
      method to specifically detect Escherichia coli O157:H7 genes in bovine faecal
      samples. METHODS AND RESULTS: A multiplex PCR method combining three primer sets
      for the E. coli O157:H7 genes rfbE, uidA and E. coli H7 fliC was developed and
      tested for sensitivity and specificity with pure cultures of 27 E. coli serotype
      O157 strains, 88 non-O157 E. coli strains, predominantly bovine in origin and
      five bacterial strains other than E. coli. The PCR method was very specific in
      the detection of E. coli O157:H7 and O157:H- strains, and the detection limit in
      seeded bovine faecal samples was <10 CFU g(-1) faeces, following an 18-h
      enrichment at 37 degrees C, and could be performed using crude DNA extracts as
      template. CONCLUSIONS: A new multiplex PCR method was developed to detect E. coli
      O157:H7 and O157:H-, and was shown to be highly specific and sensitive for these
      strains both in pure culture and in crude DNA extracts prepared from inoculated
      bovine faecal samples. SIGNIFICANCE AND IMPACT OF THE STUDY: This new multiplex
      PCR method is suitable for the rapid detection of E. coli O157:H7 and O157:H-
      genes in ruminant faecal samples.

PMID- 16599994
TI  - Characterization of horA and its flanking regions of Pediococcus damnosus ABBC478
      and development of more specific and sensitive horA PCR method.
AB  - AIMS: To characterize horA and its flanking regions of Pediococcus damnosus
      ABBC478 and, on the basis of this insight, to develop a more specific and
      sensitive horA PCR method. METHODS AND RESULTS: A plasmid harbouring the
      homologue of a hop-resistance gene, horA, was sequenced and designated pRH478.
      The nucleotide sequence and open reading frame structure of horA and its flanking
      regions of pRH478 were found to be highly similar to those of pRH45, a horA
      harbouring plasmid previously identified in Lactobacillus brevis ABBC45. The
      nucleotide sequence of the horA homologue of P. damnosus ABBC478 was 99.6%
      identical with that of horA. Based on this insight, new primers specific to horA
      were designed and compared with the previously reported specific primer pair. As
      a consequence, it was demonstrated that the new primer pair is superior in
      specificity and sensitivity. CONCLUSIONS: The newly developed horA PCR method
      allows more specific and sensitive determination of the beer-spoilage ability of
      lactic acid bacteria (LAB). SIGNIFICANCE AND IMPACT OF THE STUDY: The nucleotide
      sequences of the horA homologues were found to be essentially identical among
      distinct species of LAB, indicating that horA-specific primers can be designed
      from almost any region of the horA gene.

PMID- 16599995
TI  - In vitro activity of xanthorrhizol against Streptococcus mutans biofilms.
AB  - AIMS: We determined the effect of xanthorrhizol (XTZ) purified from the rhizome
      of Curcuma xanthorrhiza Roxb. on the Streptococcus mutans biofilms in vitro.
      METHODS AND RESULTS: The biofilms of S. mutans at different phases of growth were
      exposed to XTZ at different concentrations (5, 10 and 50 micromol l(-1)) and for
      different time exposures (1, 10, 30 and 60 min). The results demonstrated that
      the activity of XTZ in removing S. mutans biofilm was dependent on the
      concentration, exposure time and the phase growth of biofilm. A concentration of
      5 micromol l(-1) of XTZ completely inhibited biofilm formation by S. mutans at
      adherent phases of growth, whereas 50 micromol l(-1) of XTZ removed 76% of
      biofilm at plateau accumulated phase when exposed to S. mutans biofilm for 60
      min. CONCLUSIONS: Xanthorrhizol isolated from an edible plant (C. xanthorrhiza
      Roxb.) shows promise as an antibacterial agent for inhibiting and removing S.
      mutans biofilms in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: XTZ could be used
      as a potential antibacterial agent against biofilm formation by S. mutans.

PMID- 16599996
TI  - Effect of bioaugmentation of activated sludge with white-rot fungi on olive mill
      wastewater detoxification.
AB  - AIMS: To test the potential use of Phanerochaete chrysosporium and other white
      rot fungi to detoxify olive mill wastewaters (OMW) in the presence of a complex
      activated sludge. To combine the aerobic with anaerobic treatment to optimize the
      conversion of OMW in biogas. METHODS AND RESULTS: A 25-l air lift reactor was
      used to pretreat OMW by white-rot fungi. Detoxification of the OMW was monitored
      by size exclusion HPLC analysis, chemical oxygen demand (COD)/biological oxygen
      demand (BOD(5)) ratio evolution, and bioluminescence toxicity test. Anaerobic
      treatment of OMW was performed in a 12-l anaerobic filter reactor. Efficiency of
      the treatment was evaluated by organic matter removal, and biogas production. By
      comparison with the pretreatment by activated sludge only, the bioaugmentation
      with Phanerochaete chrysosporium or Trametes versicolor led to high removal of
      organic matter, decreased the COD/BOD(5) ratio and the toxicity. The subsequent
      anaerobic digestion of the OMW pretreated with activated sludge-white-rot fungi
      showed higher biomethanization yields than that pretreated with activated sludge
      only. Higher loading rates (7 g COD l(-1) day(-1)) were reached without any
      acidification or inhibition of biomethanization. CONCLUSIONS: The use of white
      rot fungi, even in the presence of complex biological consortia to detoxify OMW,
      proved to be possible and made the anaerobic digestion of OMW for methane
      production feasible. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of fungi for
      OMW reuse and energy production could be adapted to industrial applications.

PMID- 16599997
TI  - Evaluation of different DNA sampling techniques for the application of the real
      time PCR method for the quantification of cyanobacteria in water.
AB  - AIMS: To evaluate different types of sample storage and DNA extraction techniques
      for the real-time PCR quantification of cyanobacteria in water. METHODS AND
      RESULTS: Two different filter types for the cell harvest of Microcystis sp. and
      Planktothrix spp. that were either freeze-dried or stored frozen, and two
      different methods for DNA extraction were compared. DNA extraction was achieved
      by standard phenol-chloroform extraction or by a faster commercially available
      purification kit (DNeasy, QIAGEN). In general there was good agreement between
      the cell number equivalents of phycocyanin (PC) genotypes that were estimated
      using the Taq nuclease assay (TNA) between both filter types and the storing of
      samples. The standard DNA extraction procedure gave higher numbers of PC
      genotypes when compared with the DNeasy procedure. TNA results obtained from
      Planktothrix from natural samples extracted with the standard procedure revealed
      a significant correlation with the cell numbers estimated via the microscope.
      CONCLUSIONS: Freeze-drying of samples gives quantifiable data. The standard DNA
      extraction is considered to be the most reliable and accurate, although the
      DNeasy procedure is useful for early warning monitoring. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Application of quantitative genotype analysis in cyanobacteria from
      freeze-dried samples collected during recent and past sampling programmes.

PMID- 16599998
TI  - Evaluation of acid phosphatase as a confirmation test for Clostridium perfringens
      isolated from water.
AB  - AIMS: To evaluate testing for acid phosphatase as an alternative method for the
      confirmation of Clostridium perfringens isolated from water. METHODS AND RESULTS:
      Sixty-two reference strains of Clostridium were tested for their ability to
      produce acid phosphatase, as well as reduction of sulfite on tryptose sulfite
      cycloserine agar (TSC) and production of fluorescence in TSC supplemented with 4
      methylumbelliferylphosphate (MUP). Additionally 155 environmental presumptive C.
      perfringens isolates from TSC incubated at 44 degrees C were identified and
      tested for acid phosphatase production and by the conventional MNLG (testing for
      motility, nitrate reduction, lactose fermentation and gelatin liquefaction)
      confirmation procedure. Twenty-seven strains from 15 species of Clostridium
      reduced sulfite to some extent on TSC incubated at 44 degrees C, with a
      significant number of species being able to grow well at this temperature,
      indicating that a confirmation step is needed for the enumeration of C.
      perfringens on this medium. All 10 strains of C. perfringens tested, together
      with one strain each of Clostridium baratii and Clostridium rectum produced acid
      phosphatase. These also produced fluorescence on MUP supplemented TSC, as did 13
      strains of acid phosphatase negative, sulfite-reducing clostridia, representing
      nine species. Of the environmental isolates, 114 were identified as C.
      perfringens of which 108 (94.7%) were confirmed by the acid phosphatase test
      compared with 104 (91.2%) by the MNLG tests. CONCLUSIONS: Testing for acid
      phosphatase production is at least as reliable, and much simpler to perform, than
      the current standard confirmation MNLG procedure. Incorporation of MUP into TSC
      does not reliably improve the identification of presumptive C. perfringens.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Application of testing for acid phosphatase
      as a confirmation test for C. perfringens would substantially simplify the
      analysis for this bacterium from water samples, and reduce the analysis time to
      confirmed counts.

PMID- 16599999
TI  - Survival of surface ripening cultures during storage and monitoring their
      development on cheese.
AB  - AIMS: To study the survival of bacteria isolated from the surface of smear cheese
      and monitor their development during cheese ripening. METHODS AND RESULTS: The
      storage of five potential bacterial surface-ripening cheese cultures,
      Brevibacterium aurantiacum, Corynebacterium casei, Corynebacterium variable,
      Microbacterium gubbeenense and Staphylococcus saprophyticus, in maximum recovery
      diluent (MRD), containing 0.85% w/v or 5% w/v NaCl, at 21 or 4 degrees C for 40
      days, was investigated. All five strains studied survived well with a maximum
      decrease of c. 2.5 log(10) CFU ml(-1) after storage for 40 days at 4 degrees C in
      0.85% or 5% w/v NaCl. Survival, especially of C. variable, was less at 21 degrees
      C. The development of defined ripening cultures containing C. casei and
      Debaryomyces hansenii on two farmhouse cheeses was also evaluated. Using pulsed
      field gel electrophoresis (PFGE) for the bacteria and mitochondrial DNA
      restriction fragment length polymorphism (mtDNA-RFLP) for the yeast, it was shown
      that the ripening cultures could be re-isolated in high numbers, 10(8) CFU cm(-2)
      for C. casei and 10(6) CFU cm(-2) for D. hansenii, from the cheese surface after
      2.5 weeks of ripening. CONCLUSIONS: Ripening strains of surface ripening cultures
      can be stored in MRD containing 5% w/v salt at 4 degrees C for at least 40 days.
      Such cultures are recovered in high numbers from the cheese during ripening.
      SIGNIFICANCE AND IMPACT OF STUDY: This study has provided a low-cost and
      efficient way to store bacteria that could be used as ripening cultures for smear
      cheese. Such cultures can be recovered in high numbers from the cheese surface
      during ripening.

PMID- 16600001
TI  - Epidemiological interpretation of fingerprinting profiles from leptospiral
      isolates.

PMID- 16600003
TI  - Competition or collaboration--the tensions within the purchaser provider
      relationship in nurse education.
AB  - AIMS: To explore the nature of the relationship between purchasers and providers
      from the perspectives of the key individuals involved in healthcare education in
      the late 1990s. To discuss the lessons that can be learned for nursing from their
      experiences. BACKGROUND: Although the findings illustrate experiences of
      individuals at a specific time, the issues that arise have implications for
      contemporary health care, as contract use is increasing and, with the
      introduction of foundation trusts, contracts may replace Service Level
      Agreements. METHOD: The design was qualitative and the methods used were policy
      analysis and interviews. Interviews were conducted with a national, purposive
      sample of 70 participants. RESULTS: The key finding was the amount of variation
      in effectiveness of relationships. Many purchasers and providers formed strong
      partnerships but a number had fraught relationships--a situation perceived as
      detrimental to productive working. A significant issue for current healthcare was
      the reasons why relationships worked well in some institutions and were
      ineffective in others. CONCLUSIONS: There are a number of key lessons that can be
      learned about the nature of the relationship between purchasers and providers and
      applied to contemporary health care. Notably: .the value of clear policy aims;
      .the importance of context and history in shaping the relationship; .the
      necessity of ensuring that individuals involved have the ability and commitment
      to make the relationship work; .the need to view the contracting relationship as
      a dynamic 'project' that must be worked on; .the value of sharing good practice.

PMID- 16600004
TI  - Collaborative partnerships for nursing faculties and health service providers:
      what can nursing learn from business literature?
AB  - Collaborative partnerships between nursing faculties and health service providers
      are the cornerstone of successful clinical experience for nursing students. The
      challenge of providing an optimal learning environment can be enormous given the
      turbulent and rapidly changing environment in health. The present study uses the
      business literature to examine what nursing can learn from business about the
      development of successful collaborative partnerships. The characteristics of
      sound partnerships are described and a set of best practice guidelines is
      developed. The guidelines summarize the factors considered to be essential for
      the effective development of collaborative partnerships. In these times of
      nursing shortages and high turnover high quality, collaborative partnerships
      between nursing faculties and the health care sector are seen as a possible
      solution to optimize clinical learning and therefore graduate preparedness.

PMID- 16600005
TI  - Clinical leadership in contemporary clinical practice: implications for nursing
      in Australia.
AB  - BACKGROUND: Leadership in the clinical practice environment is important to
      ensure both optimal patient outcomes and successive generations of motivated and
      enthusiastic clinicians. AIM: The present paper seeks to define and describe
      clinical leadership and identify the facilitators and barriers to clinical
      leadership. We also describe strategies to develop clinical leaders in Australia.
      Key drivers to the development of nursing leaders are strategies that recognize
      and value clinical expertise. These include models of care that highlight the
      importance of the nursing role; evidence-based practice and measurement of
      clinical outcomes; strategies to empower clinicians and mechanisms to ensure
      participation in clinical decision-making. KEY ISSUES: Significant barriers to
      clinical leadership are organizational structures that preclude nurses from
      clinical decision making; the national shortage of nurses; fiscal constraints;
      absence of well evaluated models of care and trends towards less skilled
      clinicians. CONCLUSIONS: Systematic, strategic initiatives are required to
      nurture and develop clinical leaders. These strategies need to be collegial
      collaborations between the academic and health care sectors in order to provide a
      united voice for advancing the nursing profession.

PMID- 16600006
TI  - Management's role in shaping organizational culture.
AB  - AIM: The present study addresses the importance of the manager's role in the
      development and maintenance of organizational culture. It describes the types of
      cultures that exist and manager characteristics that are essential to
      facilitating a healthy workplace. BACKGROUND: While many managers do not deny the
      importance of organizational culture in employee satisfaction, few fail to
      realize the direct impact they have in shaping it. It is oftentimes believed that
      cultures are predetermined; however, this is a false assumption. It is crucial
      that managers at all levels are aware of their roles and responsibilities in
      upholding positive workplace environments that can increase employee
      satisfaction. Dissatisfaction is the major cause of turnover and can have
      detrimental cost and environmental effects on the agency. EVALUATION: Four
      critical components of culture (i.e. trust and trustworthiness, empowerment and
      delegation, consistency and mentorship) are discussed, as is the role of managers
      in turning these into positive cultural traits. The viewpoints of several
      authors, such as Stephen Covey, Mark McCormack and Charles Handy, are explored in
      relation to the development of organizational culture. Additional theories-
      Kanter's 'Theory of Organizational Empowerment', Locke's 'Goal-setting Theory'
      and the 'Social Exchange Theory'- supplement these viewpoints. CONCLUSIONS:
      Managers are always under the magnifying glass, with each action carefully
      scrutinized by subordinates. They must exercise caution when making decisions,
      ensuring that fairness and equitability exists among staff, and that ethical
      standards are upheld on a continual basis. The four cultural components, viewed
      as managerial traits of trust and trustworthiness, empowerment, consistency and
      mentorship coexist at all times regardless of the type of culture. Managers must
      put support systems and other mechanisms into place that allow employees the
      opportunity to empower themselves and to flourish, thus increasing their own
      effectiveness as well as that of the organization.

PMID- 16600007
TI  - Professionalizing action research--a meaningful strategy for modernizing
      services?
AB  - BACKGROUND: This paper outlines how a specific action research approach can be
      used to secure practice development in services which have found sustained change
      difficult. For the purpose of this paper discussion focuses upon using
      professionalizing action research (a form of action research) to secure
      transformation in acute inpatient mental health services. This speciality has
      experienced long-term difficultly in meaningful practice change. Not limited to
      this context parallels can be made with other health and social care services
      requiring significant modernization. AIM: The aim is to critically discuss the
      use of professionalizing action research as an approach to sustainable change.
      DISCUSSION: clarifies whether this method is a suitable vehicle for change, which
      is ideally suited to services which have a poor record of practice development.
      METHOD: A review of action research and practice development literature forms the
      basis of this paper. The literature is sourced through bulletin boards,
      electronic databases and the British Library Classification Scheme. Keywords
      searched are action research, team learning, managing change and practice
      development. Following definition; the components of professionalizing action
      research are analysed using the themes of educative base, problem focus,
      improvement and involvement. FINDINGS: The educative base of professionalizing
      action research is collaborative reflective practice which is used to initiate
      meaningful change, rooted in everyday practice. The benefit of this is that
      change actions are based in real-time situations. The problem focus component of
      professionalizing action research is used to emphasize the views of service users
      and carers. This is positive in terms of the patient and public involvement
      agenda although this theme does emphasize limitations of the approach. The final
      components are involvement and improvement, these are debated as pluralistic
      notions and the implications of this are acknowledged. CONCLUSION: Reviewing the
      literature and theoretical application indicates the value of professionalizing
      action research as a process for modernization. The strength of the approach lies
      in the opportunity for team learning and change which is grounded in the context
      of services and pursued through collaboration.

PMID- 16600008
TI  - Putting conflict management into practice: a nursing case study.
AB  - AIM: This paper is intended to put knowledge in conflict management into practice
      through reflecting on a nursing case study. BACKGROUND: Nursing organizations are
      particularly vulnerable to conflict as the context of nurses' work may be
      difficult and stressful. Power conflict is argued to be an important source of
      tension within nursing units. Learning to manage conflict at an early stage is
      therefore crucial to the effective functioning of nursing organizations.
      EVALUATION: A nursing case study that illustrates power conflict in an oncology
      nursing unit is displayed and reflection on conflict management from the case is
      provided. KEY ISSUES: There is no appropriate or inappropriate strategy to deal
      with conflict. However, detecting initial symptoms of conflict and adopting the
      most effective behaviour to conflict resolution is essential in nursing units.
      CONCLUSION: Further nursing education in conflict management for staff nurses and
      nurse managers is greatly needed.

PMID- 16600009
TI  - Towards an integrated approach for the management of ageing nurses.
AB  - AIM: The objective of this study is to provide an overview of the ageing of the
      nursing workforce and to explore retention strategies centred on the entire
      professional life and on all age groups. BACKGROUND: The presence of an
      increasing proportion of ageing workers presents a major challenge to the nursing
      profession. Evaluation Presentation of theories about the development of a
      healthy workplace leads to the identification of a framework on which managers
      can base their management decisions. KEY ISSUES: Examples of incentives relating
      to the framework are presented which were expressed by both nurses under 50 years
      of age and those over 50. CONCLUSIONS: Introducing incentives centred on all age
      groups provides an opportunity to create a healthy workplace for all generations
      of nurses.

PMID- 16600010
TI  - Commitment to nursing: results of a qualitative interview study.
AB  - AIM: The aims of the study were to explore opportunities to undergo continuing
      professional education, family friendly policy and holding an innovative or
      traditional post on nurses' job satisfaction and professional and organizational
      commitment. BACKGROUND: Qualified nurses have become a scare resource in the
      National Health Service. Managers need to be aware of the work-related factors
      most likely to secure nurses' professional and organizational commitment which
      will contribute to the retention. Commitment is thought to be increased if
      opportunities for continuing professional education are good. Family friendly
      policy is also important. Less is known about the relationship between type of
      nursing work and commitment. METHODS: An in-depth, exploratory approach to data
      collection were taken, employing an interview guide with open-ended questions.
      Data were collected with 27 nurses in clinical grades in two contrasting trusts.
      RESULTS: Family friendly policies emerged as most important in securing nursing
      commitment. Those in innovative posts whose work entailed social hours and
      greater professional autonomy also displayed greater levels of job satisfaction.
      Opportunities for continuing professional education had less influence on
      professional and organizational commitment. CONCLUSION: Providing flexible or
      social working hours appears to be more influential than providing opportunities
      for continuing professional education in securing nursing commitment in this
      exploratory study.

PMID- 16600011
TI  - Comparison of risk management in Taiwan and the USA.
AB  - AIM: The purpose of this paper is to compare and contrast the systems of risk
      management between a hospital in the USA and a hospital in Taiwan. BACKGROUND: By
      comparing both systems, nurses and managers will have a better understanding of
      risk management improvements and be in a better position to protect their
      patients and themselves. EVALUATION: Two interviews were conducted and literature
      were collected and reviewed by the author to support the argument. The gathered
      information was analysed to demonstrate the strengths and weaknesses of both
      hospital systems. KEY ISSUES: Although risk management is not difficult to
      understand, nurses and managers usually pay insufficient attention to it.
      CONCLUSION: Health care providers should work as a team to complete risk
      assessment and management in their workplaces. There are weaknesses to be
      improved and strengths to be continued and addressed in Taiwan and in the USA.

PMID- 16600012
TI  - Measuring nursing workload in neonatal intensive care.
AB  - AIM: To determine if a suitable method of measuring nursing workload could be
      developed in neonatal intensive care units (NICUs). BACKGROUND: Nursing is a
      multifunctioning activity and previous methods measuring the demand for nurses do
      not put enough emphasis on the individual capabilities. The reporting of NICU
      activity has traditionally been related to bed occupancy and the number of
      infants requiring ventilator support. A classification system based on activity,
      hours of care and nursing staff ratios has been used; however, it does not
      consider the clinical ability of the individual nurses. METHODS: A 5-month
      prospective study was undertaken in which nurses in two NICUs scored their
      patients' level of dependency and professional assessment of the level of
      intensity of care required by the infants in each shift. In addition, serial
      measures of severity of illness scores for each patient were collected. KEY
      ISSUES: The study identified methods of measuring workload that consider the
      individual nurse's ability and contributing organizational factors. We found that
      the estimates of nursing hours using the two traditional dependency measures did
      not match the current practice or take into account the skill of the nurses. A
      method in which the nurses indicated the intensity of nursing care required by
      their patients was suitable one for capturing their individual capabilities.
      System factors were also found to contribute to the nursing workload.
      CONCLUSIONS: It is not sufficient to use patient acuity or severity of illness
      alone. Other factors such as the nurse's assessment of the intensity of care
      required and the organizational factors are important components of workload
      estimates.

PMID- 16600013
TI  - Communication--a core concept in client supervision by public health nurses.
AB  - AIM: The aim of this study was to explore public health nurses' reflections on
      client supervision. BACKGROUND: Reflection on actions represents a possible basis
      for constructing and refining assumptions on current theories used in practice
      thus making knowledge development possible. METHODS: Transcript-based qualitative
      content analysis was used to analyse the findings from individual interviews with
      13 female public health nurses. FINDINGS: Communication is a core concept of
      client supervision by public health nurses and includes the following themes: (1)
      building a trusting relationship, (2) looking beyond the current situation, (3)
      creating a partnership and equality and (4) considering the challenge involved in
      trying to act in the clients' best interests. CONCLUSIONS: This study shows that
      public health nurses' reflection and reflecting related to their provision of
      client supervision revealed one possible assumption regarding their theories-in
      use; communication is a core concept in client supervision. Communication is
      viewed from a hermeneutic perspective--as the meaning of the interaction between
      the public health nurses and the client in the supervision is reflected upon and
      interpreted.

PMID- 16600014
TI  - Nurse and resident satisfaction in magnet long-term care organizations: do high
      involvement approaches matter?
AB  - AIM: This study examines the association of high involvement nursing work
      practices with employer-of-choice (magnet) status in a sample of Canadian nursing
      homes. BACKGROUND: In response to a severe shortage of registered nursing
      personnel, it is imperative for health care organizations to more effectively
      recruit and retain nursing personnel. Some long-term care organizations are
      developing employee-centred cultures that allow them to effectively enhance nurse
      and resident satisfaction. At the same time, many nursing homes have adopted
      progressive nursing workplace practices (high involvement work practices) that
      emphasize greater employee empowerment, participation and commitment. METHOD: A
      mail survey was sent to the director of nursing in 300 nursing homes in western
      Canada. In total, 125 useable questionnaires were returned and constituted the
      data set for this study. Separate ordinary least squares regressions are
      performed with magnet strength, nurse satisfaction and resident satisfaction used
      as dependent variables. RESULTS: Nursing homes that demonstrate strong magnet
      (employer-of-choice) characteristics are more likely to have higher levels of
      nurse and patient satisfaction, even after controlling for a number of
      significant factors at the establishment level. Magnet nursing homes are more
      likely to have progressive participatory decision-making cultures and much more
      likely to spend considerable resources on job-related training for their nursing
      staff. The presence of high involvement work practices is not found to be a
      significant predictor in magnet strength, nurse or resident satisfaction.
      CONCLUSION: Merely adopting more high involvement nursing work practices may be
      insufficient for nursing homes, which desire to become 'employers-of-choice' in
      their marketplaces, especially if these practices are adopted without a
      concomitant investment in nurse training or an enhanced commitment to
      establishing a more democratic and participatory decision-making style involving
      all nursing staff.

PMID- 16600016
TI  - Clinical and functional remission: even though biologics are superior to
      conventional DMARDs overall success rates remain low--results from RABBIT, the
      German biologics register.
AB  - We investigated the frequency of remission according to the disease activity
      score (DAS28) definition, modified American Rheumatology Association (ARA)
      criteria, and the frequency of an achievement of a functional status above
      defined thresholds ('functional remission', 'physical independence') in
      rheumatoid arthritis (RA) patients treated with either biologics or conventional
      DMARDs. We used the data of a prospective cohort study, the German biologics
      register RABBIT (German acronym for Rheumatoid Arthritis--Observation of Biologic
      Therapy) to investigate the outcomes in RA patients with two or more DMARD
      failures who received new treatment with biologics (BIOL; n = 818) or a
      conventional DMARD (n = 265). Logistic regression analysis was applied to adjust
      for differences in baseline risks. Taking risk indicators such as previous DMARD
      failures or baseline clinical status into account, we found that biologics
      doubled the chance of remission compared to conventional DMARD therapies (DAS28
      remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2
      3.2)); ARA remission, OR 2.05 (95% CI 1.2-3.5)). High remission rates (DAS28
      remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a
      moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These
      rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and
      12 months was achieved in <10% of the patients. Severely disabled patients (< or
      = 50% of full function) receiving biologic therapies were significantly more
      likely to achieve a status indicating physical independence (> or = 67% of full
      function) than controls (OR 3.88 (95% CI 1.7-8.8)). 'Functional remission' (> or
      = 83% of full function) was more often achieved in BIOL than in controls (OR 2.18
      (95% CI 1.04-4.6)). In conclusion, our study shows that biologics increase the
      chance to achieve clinical remission and a status of functional remission or at
      least physical independence. However, temporary or even sustained remission
      remain ambitious aims, which are achieved in a minority of patients only.

PMID- 16600017
TI  - Reference based annotation with GeneMapper.
AB  - We introduce GeneMapper, a program for transferring annotations from a well
      annotated genome to other genomes. Drawing on high quality curated annotations,
      GeneMapper enables rapid and accurate annotation of newly sequenced genomes and
      is suitable for both finished and draft genomes. GeneMapper uses a profile based
      approach for mapping genes into multiple species, improving upon the standard
      pairwise approach. GeneMapper is freely available for academic use.

PMID- 16600018
TI  - A survey of motif discovery methods in an integrated framework.
AB  - BACKGROUND: There has been a growing interest in computational discovery of
      regulatory elements, and a multitude of motif discovery methods have been
      proposed. Computational motif discovery has been used with some success in simple
      organisms like yeast. However, as we move to higher organisms with more complex
      genomes, more sensitive methods are needed. Several recent methods try to
      integrate additional sources of information, including microarray experiments
      (gene expression and ChlP-chip). There is also a growing awareness that
      regulatory elements work in combination, and that this combinatorial behavior
      must be modeled for successful motif discovery. However, the multitude of methods
      and approaches makes it difficult to get a good understanding of the current
      status of the field. RESULTS: This paper presents a survey of methods for motif
      discovery in DNA, based on a structured and well defined framework that
      integrates all relevant elements. Existing methods are discussed according to
      this framework. CONCLUSION: The survey shows that although no single method takes
      all relevant elements into consideration, a very large number of different models
      treating the various elements separately have been tried. Very often the choices
      that have been made are not explicitly stated, making it difficult to compare
      different implementations. Also, the tests that have been used are often not
      comparable. Therefore, a stringent framework and improved test methods are needed
      to evaluate the different approaches in order to conclude which ones are most
      promising. REVIEWERS: This article was reviewed by Eugene V. Koonin, Philipp
      Bucher (nominated by Mikhail Gelfand) and Frank Eisenhaber.

PMID- 16600019
TI  - Effects of quercetin on insulin-like growth factors (IGFs) and their binding
      protein-3 (IGFBP-3) secretion and induction of apoptosis in human prostate cancer
      cells.
AB  - BACKGROUND: Quercetin, the predominant flavonoid, has been reported to lower the
      risk of several cancers. This flavonoid found in onion, grapes, green vegetables,
      etc. has been shown to possess potent antiproliferative effects against various
      malignant cells. This study was designed to investigate its effects on insulin
      like growth factors (IGFs) and their binding protein-3 (IGFBP-3) proteins
      secretion and also apoptosis induction in the human prostate cancer cell line, PC
      3. METHODS: We evaluated the secretion of IGF-I, -II and IGFBP-3 in quercetin
      treated cells by immunoradiometric (IRMA) method. Apoptosis was studied in
      quercetin treated cells by TUNEL and DNA fragmentation. Protein expressions of
      Bcl-2, Bcl-xL, Bax and caspase-3 were studied by western blot. RESULTS: At a dose
      of 100 microM concentration, we observed increased IGFBP-3 accumulation in PC-3
      cells conditioned medium with a dose dependent increase with 2 fold over a base
      line, and significantly reduced the both IGF-I and IGF-II levels. Apoptosis
      induction was also confirmed by TUNEL assay. Bcl-2 and Bcl-xL protein expressions
      were significantly decreased and Bax and caspase-3 were increased. CONCLUSION:
      These results suggest that the decreased level of IGFs could be due to the
      increased levels of IGFBP-3, because of the high binding affinity towards IGFs,
      thereby decreasing the cell proliferation. The increased level of IGFBP-3 was
      associated with increased pro-apoptotic proteins and apoptosis in response to
      quercetin, suggesting it may be a p53-independent effector of apoptosis in
      prostate cancer cells.

PMID- 16600020
TI  - LDL cholesterol estimation in patients with the metabolic syndrome.
AB  - BACKGROUND: The Friedewald formula (LDL-F) for the estimation of low-density
      lipoprotein (LDL) cholesterol concentrations is the most often used formula in
      clinical trials and clinical practice. However, much concern has been raised as
      to whether this formula is applicable in all patient populations such as the
      presence of chylomicronaemia and/or hypertriglyceridaemia. The aim of the present
      study was to evaluate various LDL cholesterol calculation formulas as well as LDL
      cholesterol levels provided by the Lipoprint LDL System (LDL-L) in patients with
      the metabolic syndrome (MetSyn). RESULTS: LDL-F showed significant differences
      from other formulas in the total cohort, as well as in MetSyn individuals. This
      was not the case in nonMetSyn subjects, where LDL-F did not differ with other
      formulas, with the exception of one formula (LDL by Planella, LDL-P). The bias
      between LDL-F and other LDL estimation formulas were significantly higher in
      MetSyn subjects compared to nonMetSyn individuals, except for LDL-L which
      produced similar bias with LDL-F in both study groups. CONCLUSION: LDL-F seems to
      exhibit some limitations as far as the calculation of LDL-C levels in patients
      with the MetSyn is concerned. LDL-L might be more accurate in MetSyn subjects,
      but so far its use is limited for the estimation of small, dense LDL (sdLDL)
      cholesterol levels and mean LDL particle size for research purposes only.

PMID- 16600023
TI  - A novel fluorescent pH probe for expression in plants.
AB  - BACKGROUND: The pH is an important parameter controlling many metabolic and
      signalling pathways in living cells. Recombinant fluorescent pH indicators
      (pHluorins) have come into vogue for monitoring cellular pH. They are derived
      from the most popular Aequorea victoria GFP (Av-GFP). Here, we present a novel
      fluorescent pH reporter protein from the orange seapen Ptilosarcus gurneyi (Pt
      GFP) and compare its properties with pHluorins for expression and use in plants.
      RESULTS: pHluorins have a higher pH-sensitivity. However, Pt-GFP has a broader pH
      responsiveness, an excellent dynamic ratio range and a better acid stability. We
      demonstrate how Pt-GFP expressing Arabidopsis thaliana report cytosolic pH-clamp
      and changes of cytosolic pH in the response to anoxia and salt-stress.
      CONCLUSION: Pt-GFP appears to be the better choice when used for in vivo
      recording of cellular pH in plants.

PMID- 16600022
TI  - Functional characterisation of the regulation of CAAT enhancer binding protein
      alpha by GSK-3 phosphorylation of Threonines 222/226.
AB  - BACKGROUND: Glycogen Synthase Kinase-3 (GSK3) activity is repressed following
      insulin treatment of cells. Pharmacological inhibition of GSK3 mimics the effect
      of insulin on Phosphoenolpyruvate Carboxykinase (PEPCK), Glucose-6 Phosphatase
      (G6Pase) and IGF binding protein-1 (IGFBP1) gene expression. CAAT/enhancer
      binding protein alpha (C/EBPalpha) regulates these gene promoters in liver and is
      phosphorylated on two residues (T222/T226) by GSK3, although the functional
      outcome of the phosphorylation has not been established. We aimed to establish
      whether CEBPalpha is a link between GSK3 and these gene promoters. RESULTS:
      C/EBPalpha represses the IGFBP1 thymine-rich insulin response element (TIRE), but
      mutation of T222 or T226 of C/EBPalpha to non-phosphorylatable alanines has no
      effect on C/EBPalpha activity in liver cells (towards the TIRE or a consensus
      C/EBP binding sequence). Phosphorylation of T222/T226 is decreased by GSK3
      inhibition, suggesting GSK3 does phosphorylate T222/226 in intact cells. However,
      phosphorylation was not altered by treatment of liver cells with insulin.
      Meanwhile C/EBPalpha activity in 3T3 L1 preadipocytes was enhanced by mutation of
      T222/T226 and/or S230 to alanine residues. Finally, we demonstrate that
      C/EBPalpha is a very poor substrate for GSK3 in vitro and in cells. CONCLUSION:
      The work demonstrates an important role for this domain in the regulation of
      C/EBPalpha activity in adipocytes but not hepatocytes, however GSK3
      phosphorylation of these residues does not mediate regulation of this C/EBP
      activity. In short, we find no evidence that C/EBPalpha activity is regulated by
      direct phosphorylation by GSK3.

PMID- 16600024
TI  - Blood neutrophil activation markers in severe asthma: lack of inhibition by
      prednisolone therapy.
AB  - BACKGROUND: Neutrophils are increased in the airways and in induced sputum of
      severe asthma patients. We determined the expression of activation markers from
      circulating neutrophils in severe asthma, and their supressibility by
      corticosteroids. METHODS: We compared blood neutrophils from mild, moderate-to
      severe and severe steroid-dependent asthma, and non-asthmatics (n = 10 each). We
      examined the effect of adding or increasing oral prednisolone (30 mg/day;1 week).
      RESULTS: Flow cytometric expression of CD35 and CD11b, but not of CD62L or CD18,
      was increased in severe asthma. F-met-leu-phe increased CD11b, CD35 and CD18 and
      decreased CD62L expression in all groups, with a greater CD35 increase in severe
      asthma. In severe steroid-dependent asthma, an increase in prednisolone dose had
      no effect on neutrophil markers particularly CD62L, but reduced CD11b and CD62L
      on eosinophils. Phorbol myristate acetate-stimulated oxidative burst and IL-8
      release by IL-1beta, lipopolysaccharide and GM-CSF in whole blood from mild but
      not severe asthmatics were inhibited after prednisolone. There were no
      differences in myeloperoxidase or neutrophil elastase release from purified
      neutrophils. CONCLUSION: Because blood neutrophils in severe asthma are activated
      and are not inhibited by oral corticosteroids, they may be important in the
      pathogenesis of severe asthma.

PMID- 16600025
TI  - Interleukin 1 alpha is a marker of endothelial cellular senescent.
AB  - BACKGROUND: The functional changes associated with endothelial senescence may be
      involved in human aging and age-related vascular disorders. Since the
      inflammatory cytokine interleukin (IL-)1 inhibits endothelial growth, we
      evaluated the expression of IL-1alpha, IL-1beta and their antagonist, the IL-1
      receptor antagonist (IL-1ra), in endothelial in vitro senescence and quiescence.
      We also examined the expression of IL-1alpha in human senescent and progeric
      fibroblasts. RESULTS: We found that the overexpression of IL-1alpha specifically
      characterizes endothelial senescence. No modulation of this cytokine was observed
      in endothelial quiescence and in senescent or progeric human fibroblasts. The
      expression of IL-1beta and IL-1ra was also assessed and found not to be affected
      by senescence. CONCLUSION: Our results indicate that a dysfunction of the
      cytokine network associates with aging and point to a specific role of IL-1alpha
      in endothelial senescence.

PMID- 16600026
TI  - Asthma families show transmission disequilibrium of gene variants in the vitamin
      D metabolism and signalling pathway.
AB  - The vitamin D prophylaxis of rickets in pregnant women and newborns may play a
      role in early allergic sensitization. We now asked if an already diseased
      population may have inherited genetic variants in the vitamin D turnover or
      signalling pathway. Serum levels of calcidiol (25-OH-D3) and calcitriol (1,25
      (OH)2-D3) were retrospectively assessed in 872 participants of the German Asthma
      Family Study. 96 DNA single base variants in 13 different genes were genotyped
      with MALDI-TOF and a bead array system. At least one positive SNP with a TDT of p
      < 0.05 for asthma or total IgE and calcidiol or calcitriol was seen in IL10, GC,
      IL12B, CYP2R1, IL4R, and CYP24A1. Consistent strong genotypic association could
      not be observed. Haplotype association were found only for CYP24A1, the main
      calcidiol degrading enzyme, where a frequent 5-point-haplotype was associated
      with asthma (p = 0.00063), total IgE (p = 0.0014), calcidiol (p = 0.0043) and
      calcitriol (p = 0.0046). Genetic analysis of biological pathways seem to be a
      promising approach where this may be a first entry point into effects of a
      polygenic inherited vitamin D sensitivity that may affect also other metabolic,
      immunological and cancerous diseases.

PMID- 16600027
TI  - AbMiner: a bioinformatic resource on available monoclonal antibodies and
      corresponding gene identifiers for genomic, proteomic, and immunologic studies.
AB  - BACKGROUND: Monoclonal antibodies are used extensively throughout the biomedical
      sciences for detection of antigens, either in vitro or in vivo. We, for example,
      have used them for quantitation of proteins on "reverse-phase" protein lysate
      arrays. For those studies, we quality-controlled > 600 available monoclonal
      antibodies and also needed to develop precise information on the genes that
      encode their antigens. Translation among the various protein and gene identifier
      types proved non-trivial because of one-to-many and many-to-one relationships. To
      organize the antibody, protein, and gene information, we initially developed a
      relational database in Filemaker for our own use. When it became apparent that
      the information would be useful to many other researchers faced with the need to
      choose or characterize antibodies, we developed it further as AbMiner, a fully
      relational web-based database under MySQL, programmed in Java. DESCRIPTION:
      AbMiner is a user-friendly, web-based relational database of information on > 600
      commercially available antibodies that we validated by Western blot for protein
      microarray studies. It includes many types of information on the antibody, the
      immunogen, the vendor, the antigen, and the antigen's gene. Multiple gene and
      protein identifier types provide links to corresponding entries in a variety of
      other public databases, including resources for phosphorylation-specific
      antibodies. AbMiner also includes our quality-control data against a pool of 60
      diverse cancer cell types (the NCI-60) and also protein expression levels for the
      NCI-60 cells measured using our high-density "reverse-phase" protein lysate
      microarrays for a selection of the listed antibodies. Some other available
      database resources give information on antibody specificity for one or a couple
      of cell types. In contrast, the data in AbMiner indicate specificity with respect
      to the antigens in a pool of 60 diverse cell types from nine different tissues of
      origin. CONCLUSION: AbMiner is a relational database that provides extensive
      information from our own laboratory and other sources on more than 600 available
      antibodies and the genes that encode the antibodies' antigens. The data will be
      made freely available at http://discover.nci.nih.gov/abminer.

PMID- 16600028
TI  - Randomized controlled trial of Hepatitis B virus vaccine in HIV-1-infected
      patients comparing two different doses.
AB  - BACKGROUND: Co-infection with hepatitis B virus (HBV) and human immunodeficiency
      virus (HIV) is not infrequent as both share same route of exposure. The risk of
      developing chronic hepatitis B virus is 6%, in general population but can reach
      10-20% in HBV/HIV co-infected patients. When compared to general population, the
      response rate to HBV vaccine in HIV-infected patients is diminished, so previous
      studies have tried to improve this response using variety of schedules, doses and
      co-administration of immunomodulators. The purpose of this study was to evaluate
      two doses of recombinant HBV vaccine (10 or 40 microg), IM at 0, 1 and 6 months.
      Vaccination response was measured 30-50 days after last dose; titers of >9.9 IU/L
      were considered positive. RESULTS: Seventy-nine patients were included, 48
      patients (60.7%) serconverted. Thirty-nine patients (49.3%) received 10 microg
      vaccine dose, 24 patients (61.5%) seroconverted. Forty patients (50.7%) received
      40 microg vaccine dose, 24 (60%) seroconverted. There were no differences between
      two doses. A statistically significant higher seroconversion rate was found for
      patients with CD4 cell counts at vaccination > or = 200 cel/mm3 (33 of 38
      patients, 86.8%), compared with those with CD4 < 200 cel/mm3 (15 of 41, 36.6%),
      [OR 11.44, 95% IC 3.67-35.59, p = 0.003], there were no differences between two
      vaccine doses. Using the logistic regression model, CD4 count <200 cel/mm3 were
      significantly associated with non serologic response (p = 0.003). None other
      variables such as gender, age, risk exposure for HIV, viral load, type or
      duration of HAART or AIDS-defining illness, were associated with seroconversion.
      CONCLUSION: In this study, an increase dose of HBV vaccine did not show to
      increase the rate of response in HIV infected subjects. The only significant
      findings associated to the response rate was that a CD4 count > or = 200 cel/mm3,
      we suggest this threshold at which HIV patients should be vaccinated.

PMID- 16600029
TI  - Molecular characterization of the HIV-1 gag nucleocapsid gene associated with
      vertical transmission.
AB  - BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) nucleocapsid (NC)
      plays a pivotal role in the viral lifecycle: including encapsulating the viral
      genome, aiding in strand transfer during reverse transcription, and packaging two
      copies of the viral genome into progeny virions. Another gag gene product, p6,
      plays an integral role in successful viral budding from the plasma membrane and
      inclusion of the accessory protein Vpr within newly budding virions. In this
      study, we have characterized the gag NC and p6 genes from six mother-infant pairs
      following vertical transmission by performing phylogenetic analysis and by
      analyzing the degree of genetic diversity, evolutionary dynamics, and
      conservation of functional domains. RESULTS: Phylogenetic analysis of 168 gag NC
      and p6 genes sequences revealed six separate subtrees that corresponded to each
      mother-infant pair, suggesting that epidemiologically linked individuals were
      closer to each other than epidemiologically unlinked individuals. A high
      frequency (92.8%) of intact open reading frames of NC and p6 with patient and
      pair specific sequence motifs were conserved in mother-infant pairs' sequences.
      Nucleotide and amino acid distances showed a lower degree of viral heterogeneity,
      and a low degree of estimates of genetic diversity was also found in NC and p6
      sequences. The NC and p6 sequences from both mothers and infants were found to be
      under positive selection pressure. The two important functional motifs within NC,
      the zinc-finger motifs, were highly conserved in most of the sequences, as were
      the gag p6 Vpr binding, AIP1 and late binding domains. Several CTL recognition
      epitopes identified within the NC and p6 genes were found to be mostly conserved
      in 6 mother-infant pairs' sequences. CONCLUSION: These data suggest that the gag
      NC and p6 open reading frames and functional domains were conserved in mother
      infant pairs' sequences following vertical transmission, which confirms the
      critical role of these gene products in the viral lifecycle.

PMID- 16600030
TI  - Social support, physical activity and sedentary behavior among 6th-grade girls: a
      cross-sectional study.
AB  - BACKGROUND: Despite the importance of social support in promoting physical
      activity, little is known about the relative influence of the type or source of
      social support on adolescent girls' physical activity and sedentary behaviors.
      This study examined the associations of two types of social support (social
      participation in and social encouragement for physical activity) and two social
      support sources (family and friends) with self-reported daily minutes of physical
      activity and sedentary behavior among sixth-grade girls in Texas. METHODS: A
      secondary analysis of 718 sixth-grade girls between the ages of 10 to 14 was
      performed using cross-sectional baseline data from an osteoporosis prevention
      intervention study. Physical activity and sedentary behaviors (television-video
      viewing and computer-video game playing) were assessed using 3 administrations of
      the Self-Administered Physical Activity Checklist; social support indicators were
      assessed with Likert-type items from a psychosocial questionnaire. RESULTS: In
      multiple linear regression analyses, friend physical activity participation
      (partial correlation coefficient (r) = 0.10, p = .009) and friend (r = 0.12) and
      family encouragement (r = 0.11) (p < .01, respectively) were positively related
      to moderate-to-vigorous physical activity in the full model with other support
      variables, BMI and ethnicity; friend encouragement was the only variable
      positively related to vigorous physical activity (r = 0.11, p = .005). Family
      participation in physical activity had the strongest negative correlation with
      total minutes of television-video viewing and computer-video playing (r = -0.08,
      p < .05). CONCLUSION: Findings lend support to the importance of social support
      for physical activity among adolescent girls but suggest that the source and type
      of social support may differ for physical activity and sedentary behaviors.
      Further research is needed to assess the causal or reciprocal relation between
      the roles of friends and family in promoting physical activity and of family
      physical activity in decreasing sedentary behaviors among early adolescent girls.

PMID- 16600031
TI  - Operational strategies, monitoring and control of heterologous protein production
      in the methylotrophic yeast Pichia pastoris under different promoters: a review.
AB  - The methylotrophic yeast Pichia pastoris has been widely reported as a suitable
      expression system for heterologous protein production. The use of different
      phenotypes under PAOX promoter, other alternative promoters, culture medium, and
      operational strategies with the objective to maximize either yield or
      productivity of the heterologous protein, but also to obtain a repetitive product
      batch to batch to get a robust process for the final industrial application have
      been reported. Medium composition, kinetics growth, fermentation operational
      strategies from fed-batch to continuous cultures using different phenotypes with
      the most common PAOX promoter and other novel promoters (GAP, FLD, ICL), the use
      of mixed substrates, on-line monitoring of the key fermentation parameters
      (methanol) and control algorithms applied to the bioprocess are reviewed and
      discussed in detail.

PMID- 16600032
TI  - WFDC2 (HE4): a potential role in the innate immunity of the oral cavity and
      respiratory tract and the development of adenocarcinomas of the lung.
AB  - BACKGROUND: The Whey Acidic Protein domain is an evolutionarily conserved motif
      found in a number of proteins, the best studied of which are antiproteinases
      involved in the innate immune defence of multiple epithelia. We recently
      characterised the WFDC2 gene which encodes a two WAP domain-containing protein,
      initially suggested as a marker for epididymis, and showed that it is highly
      expressed in the lung and salivary gland. The precise location of WFDC2 protein
      in these sites has not been described. METHODS: We used immunohistochemistry to
      localise WFDC2 in normal tissues of the respiratory tract, naso- and oropharynx,
      as well as in chronically inflamed lung from Cystic Fibrosis and a range of
      pulmonary carcinomas. We have complemented these studies with molecular analysis
      of WFDC2 gene expression in primary human lung cell cultures. RESULTS: WFDC2 is
      expressed in some epithelial cells of the upper airways as well as in mucous
      cells and ducts of submucosal glands. No staining was seen in peripheral lung.
      Intense staining is found in major salivary glands and in minor glands of the
      nose, sinuses, posterior tongue and tonsil. Studies with the related protein
      Secretory Leukocyte Protease Inhibitor (SLPI) show that although both proteins
      are expressed in similar tissues, the precise cellular localisation differs.
      Significant increases in expression and localisation of WFDC2 are seen in
      patients with Cystic Fibrosis. SLPI expression was greatly reduced in the same
      samples. In cultures of tracheobronchial epithelial cells, expression of WFDC2
      and SLPI are differentially regulated during differentiation yet WFDC2 is not
      induced by pro-inflammatory mediators. The majority of adenocarcinomas stain with
      WFDC2 whilst a significant minority of squamous, small cell and large cell
      carcinomas exhibit focal staining. There is no clear association with tumour
      grade. CONCLUSION: We believe that these studies support the hypothesis that
      WFDC2 may be a component of the innate immune defences of the lung, nasal and
      oral cavities and suggest that WFDC2 functions in concert with related WAP domain
      containing proteins in epithelial host defence. We also suggest that WFDC2 re
      expression in lung carcinomas may prove to be associated with tumour type and
      should be studied in further detail.

PMID- 16600033
TI  - Treatment and outcome of CPD-associated peritonitis.
AB  - CPD-associated peritonitis is a leading cause of morbidity and mortality for ESRD
      patients maintained on CPD therapy. The percentage of ESRD patients maintained on
      CPD therapy is declining. The reasons are unclear, but may be due to concerns
      about CPD-associated peritonitis. The incidence of CPD-associated peritonitis has
      decreased largely attributed to technical advances and the identification of risk
      factors including exit-site infection, colonization with Staphylococcus aureus
      and depression. The typical spectrum of organisms causing peritonitis include
      gram-positive organisms (67%), gram-negative organisms (28%), fungi (2.5%) or
      anaerobic organisms (2.5%). Culture-negative episodes do occur: up to 20% of the
      episodes of peritonitis in some series are culture-negative. The treatment of CPD
      associated peritonitis is rather standardized with current recommendations by the
      International Society of Peritoneal Dialysis universally adopted. Approximately
      80% of the patients developing peritonitis will respond to antimicrobial therapy
      and remain on CPD therapy, while 10 to 15% of the patients require catheter
      removal and transfer to hemodialysis. Approximately 6% of the patients expire as
      a result of peritonitis. The outcome is different based on organism with gram
      negative and fungal episodes having a worse outcome than gram-positive episodes.
      The development of CPD-associated peritonitis can be linked to traditional risk
      factors such as exit-site infection and poor technique. Bacterial biofilm has
      also been suggested as a cause of peritonitis. Our current antimicrobial
      protocols may not permit adequate dosing to penetrate the biofilm and be a reason
      for recurrent or repeat episodes of peritonitis. It is important that we improve
      our understanding of factors responsible for the development and outcome of CPD
      associated peritonitis in order for this renal replacement therapy to remain a
      viable option for patients with ESRD.

PMID- 16600034
TI  - Global gene expression analyses of hematopoietic stem cell-like cell lines with
      inducible Lhx2 expression.
AB  - BACKGROUND: Expression of the LIM-homeobox gene Lhx2 in murine hematopoietic
      cells allows for the generation of hematopoietic stem cell (HSC)-like cell lines.
      To address the molecular basis of Lhx2 function, we generated HSC-like cell lines
      where Lhx2 expression is regulated by a tet-on system and hence dependent on the
      presence of doxycyclin (dox). These cell lines efficiently down-regulate Lhx2
      expression upon dox withdrawal leading to a rapid differentiation into various
      myeloid cell types. RESULTS: Global gene expression of these cell lines cultured
      in dox was compared to different time points after dox withdrawal using
      microarray technology. We identified 267 differentially expressed genes. The
      majority of the genes overlapping with HSC-specific databases were those down
      regulated after turning off Lhx2 expression and a majority of the genes
      overlapping with those defined as late progenitor-specific genes were the up
      regulated genes, suggesting that these cell lines represent a relevant model
      system for normal HSCs also at the level of global gene expression. Moreover, in
      situ hybridisations of several genes down-regulated after dox withdrawal showed
      overlapping expression patterns with Lhx2 in various tissues during embryonic
      development. CONCLUSION: Global gene expression analysis of HSC-like cell lines
      with inducible Lhx2 expression has identified genes putatively linked to self
      renewal/differentiation of HSCs, and function of Lhx2 in organ development and
      stem/progenitor cells of non-hematopoietic origin.

PMID- 16600035
TI  - The PLAC1-homology region of the ZP domain is sufficient for protein
      polymerisation.
AB  - BACKGROUND: Hundreds of extracellular proteins polymerise into filaments and
      matrices by using zona pellucida (ZP) domains. ZP domain proteins perform highly
      diverse functions, ranging from structural to receptorial, and mutations in their
      genes are responsible for a number of severe human diseases. Recently, PLAC1,
      Oosp1-3, Papillote and CG16798 proteins were identified that share sequence
      homology with the N-terminal half of the ZP domain (ZP-N), but not with its C
      terminal half (ZP-C). The functional significance of this partial conservation is
      unknown. RESULTS: By exploiting a highly engineered bacterial strain, we
      expressed in soluble form the PLAC1-homology region of mammalian sperm receptor
      ZP3 as a fusion to maltose binding protein. Mass spectrometry showed that the 4
      conserved Cys residues within the ZP-N moiety of the fusion protein adopt the
      same disulfide bond connectivity as in full-length native ZP3, indicating that it
      is correctly folded, and electron microscopy and biochemical analyses revealed
      that it assembles into filaments. CONCLUSION: These findings provide a function
      for PLAC1-like proteins and, by showing that ZP-N is a biologically active
      folding unit, prompt a re-evaluation of the architecture of the ZP domain and its
      polymers. Furthermore, they suggest that ZP-C might play a regulatory role in the
      assembly of ZP domain protein complexes.

PMID- 16600036
TI  - Incidence of post myocardial infarction left ventricular thrombus formation in
      the era of primary percutaneous intervention and glycoprotein IIb/IIIa
      inhibitors. A prospective observational study.
AB  - BACKGROUND: Before the widespread use of primary percutaneous coronary
      intervention (PCI) and glycoprotein IIb/IIIa inhibitors (GP IIb/IIIa) left
      ventricular (LV) thrombus formation had been reported to complicate up to 20% of
      acute myocardial infarctions (AMI). The incidence of LV thrombus formation with
      these treatment modalities is not well known. METHODS: 92 consecutive patients
      with ST-elevation AMI treated with PCI and GP IIb/IIIa inhibitors underwent 2-D
      echocardiograms, with and without echo contrast agent, within 24-72 hours.
      RESULTS: Only 4/92 (4.3%) had an LV thrombus, representing a significantly lower
      incidence than that reported in the pre-PCI era. Use of contrast agents did not
      improve detection of LV thrombi in our study. CONCLUSION: The incidence of LV
      thrombus formation after acute MI, in the current era of rapid reperfusion, is
      lower than what has been historically reported.

PMID- 16600037
TI  - Genotyping of Bacillus anthracis strains based on automated capillary 25-loci
      multiple locus variable-number tandem repeats analysis.
AB  - BACKGROUND: The genome of Bacillus anthracis, the etiological agent of anthrax,
      is highly monomorphic which makes differentiation between strains difficult. A
      Multiple Locus Variable-number tandem repeats (VNTR) Analysis (MLVA) assay based
      on 20 markers was previously described. It has considerable discrimination power,
      reproducibility, and low cost, especially since the markers proposed can be typed
      by agarose-gel electrophoresis. However in an emergency situation, faster
      genotyping and access to representative databases is necessary. RESULTS:
      Genotyping of B. anthracis reference strains and isolates from France and Italy
      was done using a 25 loci MLVA assay combining 21 previously described loci and 4
      new ones. DNA was amplified in 4 multiplex PCR reactions and the length of the
      resulting 25 amplicons was estimated by automated capillary electrophoresis. The
      results were reproducible and the data were consistent with other gel based
      methods once differences in mobility patterns were taken into account. Some
      alleles previously unresolved by agarose gel electrophoresis could be resolved by
      capillary electrophoresis, thus further increasing the assay resolution. One
      particular locus, Bams30, is the result of a recombination between a 27 bp tandem
      repeat and a 9 bp tandem repeat. The analysis of the array illustrates the
      evolution process of tandem repeats. CONCLUSION: In a crisis situation of
      suspected bioterrorism, standardization, speed and accuracy, together with the
      availability of reference typing data are important issues, as illustrated by the
      2001 anthrax letters event. In this report we describe an upgrade of the
      previously published MLVA method for genotyping of B. anthracis and apply the
      method to the typing of French and Italian B. anthracis strain collections. The
      increased number of markers studied compared to reports using only 8 loci greatly
      improves the discrimination power of the technique. An Italian strain belonging
      to the B branch was described, and two new branches, D and E, are proposed. Owing
      to the upgrading achieved here, precise genotyping can now be produced either by
      automated capillary electrophoresis, or by the more accessible but slower and for
      some markers slightly less accurate agarose gel methodology.

PMID- 16600038
TI  - A comparative analysis of chiropractic and general practitioner patients in North
      America: findings from the joint Canada/United States Survey of Health, 2002-03.
AB  - BACKGROUND: Scientifically rigorous general population-based studies comparing
      chiropractic with primary-care medical patients within and between countries have
      not been published. The objective of this study is to compare care seekers of
      doctors of chiropractic (DCs) and general practitioners (GPs) in the United
      States and Canada on a comprehensive set of sociodemographic, quality of life,
      and health-related variables. METHODS: Data are from the Joint Canada/U.S. Survey
      of Health (JCUSH), 2002-03, a random sample of adults in Canada (N = 3505) and
      the U.S. (N = 5183). Respondents were categorized according to their pattern of
      health-care use in the past year. Distributions, percentages, and estimates
      (adjusted odds ratios) weighted to reflect the complex survey design were
      produced. RESULTS: Nearly 80% of respondents sought care from GPs; 12% sought DC
      care. Compared with GP only patients, DC patients in both countries tend to be
      under 65 and white, with arthritis and disabling back or neck pain. U.S. DC
      patients are more likely than GP only patients to be obese and to lack a regular
      doctor; Canadian DC patients are more likely than GP only patients to be college
      educated, to have higher incomes, and dissatisfied with MD care. Compared with
      seekers of both GP and DC care, DC only patients in both countries have fewer
      chronic conditions, take fewer drugs, and have no regular doctor. U.S. DC only
      patients are more likely than GP+DC patients to be uninsured and dissatisfied
      with health care; Canadian DC only patients are more likely than GP+DC patients
      to be under 45, male, less educated, smokers, and not obese, without disabling
      back or neck pain, on fewer drugs, and lacking a regular doctor. CONCLUSION:
      Chiropractic and GP patients are dissimilar in both Canada and the U.S., with key
      differences between countries and between DC patients who do and do not seek care
      from GPs. Such variation has broad and potentially far-reaching health policy and
      research implications.

PMID- 16600039
TI  - The Bacillus anthracis chromosome contains four conserved, excision-proficient,
      putative prophages.
AB  - BACKGROUND: Bacillus anthracis is considered to be a recently emerged clone
      within the Bacillus cereus sensu lato group. The B. anthracis genome sequence
      contains four putative lambdoid prophages. We undertook this study in order to
      understand whether the four prophages are unique to B. anthracis and whether they
      produce active phages. RESULTS: More than 300 geographically and temporally
      divergent isolates of B. anthracis and its near neighbors were screened by PCR
      for the presence of specific DNA sequences from each prophage region. Every
      isolate of B. anthracis screened by PCR was found to produce all four phage
      specific amplicons whereas none of the non-B. anthracis isolates, produced more
      than one phage-specific amplicon. Excision of prophages could be detected by a
      PCR based assay for attP sites on extra-chromosomal phage circles and for attB
      sites on phage-excised chromosomes. SYBR-green real-time PCR assays indicated
      that prophage excision occurs at very low frequencies (2 x 10(-5) - 8 x 10(
      8)/cell). Induction with mitomycin C increased the frequency of excision of one
      of the prophages by approximately 250 fold. All four prophages appear to be
      defective since, mitomycin C induced culture did not release any viable phage
      particle or lyse the cells or reveal any phage particle under electron
      microscopic examination. CONCLUSION: The retention of all four putative prophage
      regions across all tested strains of B. anthracis is further evidence of the very
      recent emergence of this lineage and the prophage regions may be useful for
      differentiating the B. anthracis chromosome from that of its neighbors. All four
      prophages can excise at low frequencies, but are apparently defective in phage
      production.

PMID- 16600040
TI  - A biobank management model applicable to biomedical research.
AB  - BACKGROUND: The work of Research Ethics Boards (REBs), especially when involving
      genetics research and biobanks, has become more challenging with the growth of
      biotechnology and biomedical research. Some REBs have even rejected research
      projects where the use of a biobank with coded samples was an integral part of
      the study, the greatest fear being the lack of participant protection and
      uncontrolled use of biological samples or related genetic data. The risks of
      discrimination and stigmatization are a recurrent issue. In light of the
      increasing interest in biomedical research and the resulting benefits to the
      health of participants, it is imperative that practical solutions be found to the
      problems associated with the management of biobanks: namely, protecting the
      integrity of the research participants, as well as guaranteeing the security and
      confidentiality of the participant's information. METHODS: We aimed to devise a
      practical and efficient model for the management of biobanks in biomedical
      research where a medical archivist plays the pivotal role as a data-protection
      officer. The model had to reduce the burden placed on REBs responsible for the
      evaluation of genetics projects and, at the same time, maximize the protection of
      research participants. RESULTS: The proposed model includes the following: 1) a
      means of protecting the information in biobanks, 2) offers ways to provide follow
      up information requested about the participants, 3) protects the participant's
      confidentiality and 4) adequately deals with the ethical issues at stake in
      biobanking. CONCLUSION: Until a governmental governance body is established in
      Quebec to guarantee the protection of research participants and establish
      harmonized guidelines for the management of biobanks in medical research, it is
      definitely up to REBs to find solutions that the present lack of guidelines
      poses. The model presented in this article offers a practical solution on a day
      to-day basis for REBs, as well as researchers by promoting an archivist to a
      pivotal role in the process. It assures protection of all participants who
      altruistically donate their samples to generate and improve knowledge for better
      diagnosis and medical treatment.

PMID- 16600041
TI  - The role of the AFD neuron in C. elegans thermotaxis analyzed using femtosecond
      laser ablation.
AB  - BACKGROUND: Caenorhabditis elegans actively crawls down thermal gradients until
      it reaches the temperature of its prior cultivation, exhibiting what is called
      cryophilic movement. Implicit in the worm's performance of cryophilic movement is
      the ability to detect thermal gradients, and implicit in regulating the
      performance of cryophilic movement is the ability to compare the current
      temperature of its surroundings with a stored memory of its cultivation
      temperature. Several lines of evidence link the AFD sensory neuron to
      thermotactic behavior, but its precise role is unclear. A current model contends
      that AFD is part of a thermophilic mechanism for biasing the worm's movement up
      gradients that counterbalances the cryophilic mechanism for biasing its movement
      down gradients. RESULTS: We used tightly-focused femtosecond laser pulses to
      dissect the AFD neuronal cell bodies and the AFD sensory dendrites in C. elegans
      to investigate their contribution to cryophilic movement. We establish that
      femtosecond laser ablation can exhibit submicrometer precision, severing
      individual sensory dendrites without causing collateral damage. We show that
      severing the dendrites of sensory neurons in young adult worms permanently
      abolishes their sensory contribution without functional regeneration. We show
      that the AFD neuron regulates a mechanism for generating cryophilic bias, but we
      find no evidence that AFD laser surgery reduces a putative ability to generate
      thermophilic bias. In addition, although disruption of the AIY interneuron causes
      worms to exhibit cryophilic bias at all temperatures, we find no evidence that
      laser killing the AIZ interneuron causes thermophilic bias at any temperature.
      CONCLUSION: We conclude that laser surgical analysis of the neural circuit for
      thermotaxis does not support a model in which AFD opposes cryophilic bias by
      generating thermophilic bias. Our data supports a model in which the AFD neuron
      gates a mechanism for generating cryophilic bias.

PMID- 16600042
TI  - A proposed mechanism for progesterone regulation of trophoblast MMP2
      transcription independent of classical progesterone response elements on its
      promoter.
AB  - BACKGROUND: Progesterone receptor act as ligand-inducible transcription factor in
      the respective target cells by binding to specific progesterone response elements
      in the promoter of the target genes. However, despite the lack of the classical
      progesterone response elements on matrix-metalloproteinase-2 promoter,
      progesterone has been shown to decrease the activity of this promoter.
      PRESENTATION OF THE HYPOTHESIS: It has recently been suggested that in addition
      to interacting with their classical co-activators and co-repressors, progesterone
      receptor are capable of binding to several transcription factors. By interacting
      with other classes of transcription factors, progesterone receptor is capable of
      transcriptional activation through the transcription factors cognate DNA binding
      site. TESTING THE HYPOTHESIS: Exploring transcription factors and transcription
      binding sites, interacting with the progesterone receptor in modulation of the
      matrix-metalloproteinase promoter. IMPLICATIONS OF THE HYPOTHESIS: Identification
      of additional endogenous progesterone target genes makes it possible to further
      explore the signaling mechanisms by which the hormone regulates biological
      actions. Furthermore, the concepts of ligand-driven conformational diversity and
      selective tissue actions can be exploited in the future for drug development
      which selectively regulate orphan receptors from the nuclear receptor family.

PMID- 16600044
TI  - Regional differences in multidimensional aspects of health: findings from the MRC
      cognitive function and ageing study.
AB  - BACKGROUND: Differences in mortality and health experience across regions are
      well recognised and UK government policy aims to address this inequality. Methods
      combining life expectancy and health have concentrated on specific areas, such as
      self-perceived health and dementia. Few have looked within country or across
      different areas of health. Self-perceived health, self-perceived functional
      impairment and cognitive impairment are linked closely to survival, as well as
      quality of life. This paper aims to describe regional differences in healthy life
      expectancy using a variety of states of health and wellbeing within the MRC
      Cognitive Function and Ageing Study (MRC CFAS). METHODS: MRC CFAS is a population
      based study of health in 13,009 individuals aged 65 years and above in five
      centres using identical study methodology. The interviews included self-perceived
      health and measures of functional and cognitive impairment. Sullivan's method was
      used to combine prevalence rates for cognitive and functional impairment and life
      expectancy to produce expectation of life in various health states. RESULTS: The
      prevalence of both cognitive and functional impairment increases with age and was
      higher in women than men, with marked centre variation in functional impairment
      (Newcastle and Gwynedd highest impairment). Newcastle had the shortest life
      expectancy of all the sites, Cambridgeshire and Oxford the longest. Centre
      differences in self-perceived health tended to mimic differences in life
      expectancy but this did not hold for cognitive or functional impairment.
      CONCLUSION: Self-perceived health does not show marked variation with age or sex,
      but does across centre even after adjustment for impairment burden. There is
      considerable centre variation in self-reported functional impairment but not
      cognitive impairment. Only variation in self-perceived health relates to the
      ranking of life expectancy. These data confirm that quite considerable
      differences in life experience exist across regions of the UK beyond basic life
      expectancy.

PMID- 16600045
TI  - An interactive tool for visualization of relationships between gene expression
      profiles.
AB  - BACKGROUND: Application of phenetic methods to gene expression analysis proved to
      be a successful approach. Visualizing the results in a 3-dimentional space may
      further enhance these techniques. RESULTS: We designed and built TreeBuilder3D,
      an interactive viewer for visualizing the hierarchical relationships between
      expression profiles such as SAGE libraries or microarrays. The program allows
      loading expression data as plain text files and visualizing the relative
      differences of the analyzed datasets in 3-dimensional space using various
      distance metrics. CONCLUSION: TreeBuilder3D provides a simple interface and has a
      small size. Written in Java, TreeBuilder3D is a platform-independent, open source
      application, which may be useful in analysis of large-scale gene expression data.

PMID- 16600046
TI  - Knock-out of SO1377 gene, which encodes the member of a conserved hypothetical
      bacterial protein family COG2268, results in alteration of iron metabolism,
      increased spontaneous mutation and hydrogen peroxide sensitivity in Shewanella
      oneidensis MR-1.
AB  - BACKGROUND: Shewanella oneidensis MR-1 is a facultative, gram-negative bacterium
      capable of coupling the oxidation of organic carbon to a wide range of electron
      acceptors such as oxygen, nitrate and metals, and has potential for
      bioremediation of heavy metal contaminated sites. The complete 5-Mb genome of S.
      oneidensis MR-1 was sequenced and standard sequence-comparison methods revealed
      approximately 42% of the MR-1 genome encodes proteins of unknown function.
      Defining the functions of hypothetical proteins is a great challenge and may need
      a systems approach. In this study, by using integrated approaches including whole
      genomic microarray and proteomics, we examined knockout effects of the gene
      encoding SO1377 (gi24372955), a member of the conserved, hypothetical, bacterial
      protein family COG2268 (Clusters of Orthologous Group) in bacterium Shewanella
      oneidensis MR-1, under various physiological conditions. RESULTS: Compared with
      the wild-type strain, growth assays showed that the deletion mutant had a
      decreased growth rate when cultured aerobically, but not affected under anaerobic
      conditions. Whole-genome expression (RNA and protein) profiles revealed numerous
      gene and protein expression changes relative to the wild-type control, including
      some involved in iron metabolism, oxidative damage protection and respiratory
      electron transfer, e. g. complex IV of the respiration chain. Although total
      intracellular iron levels remained unchanged, whole-cell electron paramagnetic
      resonance (EPR) demonstrated that the level of free iron in mutant cells was 3
      times less than that of the wild-type strain. Siderophore excretion in the mutant
      also decreased in iron-depleted medium. The mutant was more sensitive to hydrogen
      peroxide and gave rise to 100 times more colonies resistant to gentamicin or
      kanamycin. CONCLUSION: Our results showed that the knock-out of SO1377 gene had
      pleiotropic effects and suggested that SO1377 may play a role in iron homeostasis
      and oxidative damage protection in S. oneidensis MR-1.

PMID- 16600047
TI  - Expression of HIV receptors, alternate receptors and co-receptors on tonsillar
      epithelium: implications for HIV binding and primary oral infection.
AB  - BACKGROUND: Primary HIV infection can develop from exposure to HIV in the oral
      cavity. In previous studies, we have documented rapid and extensive binding of
      HIV virions in seminal plasma to intact mucosal surfaces of the palatine tonsil
      and also found that virions readily penetrated beneath the tissue surfaces. As
      one approach to understand the molecular interactions that support HIV virion
      binding to human mucosal surfaces, we have examined the distribution of the
      primary HIV receptor CD4, the alternate HIV receptors heparan sulfate
      proteoglycan (HS) and galactosyl ceramide (GalCer) and the co-receptors CXCR4 and
      CCR5 in palatine tonsil. RESULTS: Only HS was widely expressed on the surface of
      stratified squamous epithelium. In contrast, HS, GalCer, CXCR4 and CCR5 were all
      expressed on the reticulated epithelium lining the tonsillar crypts. We have
      observed extensive variability, both across tissue sections from any tonsil and
      between tonsils, in the distribution of epithelial cells expressing either CXCR4
      or CCR5 in the basal and suprabasal layers of stratified epithelium. The general
      expression patterns of CXCR4, CCR5 and HS were similar in palatine tonsil from
      children and adults (age range 3-20). We have also noted the presence of small
      clusters of lymphocytes, including CD4+ T cells within stratified epithelium and
      located precisely at the mucosal surfaces. CD4+ T cells in these locations would
      be immediately accessible to HIV virions. CONCLUSION: In total, the likelihood of
      oral HIV transmission will be determined by macro and micro tissue architecture,
      cell surface expression patterns of key molecules that may bind HIV and the
      specific properties of the infectious inoculum.

PMID- 16600048
TI  - Ventilator associated pneumonia and infection control.
AB  - Ventilator associated pneumonia (VAP) is the leading cause of morbidity and
      mortality in intensive care units. The incidence of VAP varies from 7% to 70% in
      different studies and the mortality rates are 20-75% according to the study
      population. Aspiration of colonized pathogenic microorganisms on the oropharynx
      and gastrointestinal tract is the main route for the development of VAP. On the
      other hand, the major risk factor for VAP is intubation and the duration of
      mechanical ventilation. Diagnosis remains difficult, and studies showed the
      importance of early initiation of appropriate antibiotic for prognosis. VAP
      causes extra length of stay in hospital and intensive care units and increases
      hospital cost. Consequently, infection control policies are more rational and
      will save money.

PMID- 16600049
TI  - Prevention and treatment of recurrent Hepatitis B after liver transplantation:
      the current role of nucleoside and nucleotide analogues.
AB  - The Hepatitis B virus (HBV) is a DNA virus that can cause both acute and chronic
      liver disease in humans. Approximately 350-400 million people are affected
      worldwide and up to one million deaths occur annually from cirrhosis and
      hepatocellular carcinoma. When cirrhosis and liver failure develop, the
      definitive treatment of choice remains orthotopic liver transplantation (OLT). In
      the past, an unacceptable HBV recurrence rate with a high rate of graft loss was
      noted. The use of Hepatitis B immunoglobulin (HBIG) has resulted in improved
      patient and graft survival rates. The addition of the nucleoside analog
      Lamivudine (LAM) to HBIG has improved these survival curves to an even greater
      degree. Prolonged use of LAM will almost invariably lead to the development of
      viral mutations resistant to the drug. There are now several other nucleoside and
      nucleotide analogs (Adefovir, Entecavir, Tenofovir, and Truvada) available for
      the clinician to utilize against these resistant strains. It should be possible
      to prevent recurrence in most, if not all, post-transplant patients and also to
      significantly reduce viral loads with normalization of transaminases in those who
      have developed recurrent infection. The antiviral regimen should be robust and
      minimize the risk of breakthrough mutations. A prudent approach may be the
      implication of combination antiviral therapy. This review summarizes the efficacy
      of previous regimens utilized to prevent and treat recurrent HBV following OLT.
      Particular attention will be paid to the newer nucleoside and nucleotide analogs
      and the direction for future strategies to treat HBV in the post transplant
      setting.

PMID- 16600050
TI  - Antiretroviral therapy at a district hospital in Ethiopia prevents death and
      tuberculosis in a cohort of HIV patients.
AB  - BACKGROUND: Although highly active antiretroviral therapy (HAART) reduces
      mortality in the developed world, it remains undocumented in resource-poor
      settings. We assessed the effect of HAART on patient mortality and tuberculosis
      incidence rate under routine clinical care conditions in Ethiopia. The objective
      of this study was to assess the effect of HAART on patient mortality and
      tuberculosis incidence rate under routine clinical care conditions in a resource
      limited setting in south Ethiopia. Starting in January 2003, we followed all
      consecutive adult HIV infected patients who visited the HIV clinic. Since August
      2003, we treated patients with HAART. Only basic laboratory services were
      available. RESULTS: We followed 185 patients in the pre-HAART cohort and 180
      patients in the HAART cohort. The mortality rate was 15.4 per 100 person-years of
      observation (PYO) in the HAART group and tuberculosis incidence rate was 3.7 per
      100 PYO. In the pre-HAART group, the mortality rate was 58.1 per 100 PYO and the
      tuberculosis incidence rate was 11.1 per 100 PYO. HAART resulted in a 65% decline
      in mortality (adjusted hazard ratio [95%CI] = 0.35 [0.19-0.63]; P < 0.001).
      Tuberculosis incidence rate was lower in the HAART group (adjusted hazard ratio
      [95%CI] = 0.11 [0.03-0.48]; P < 0.01). Most of the deaths occurred during the
      first three months of treatment. CONCLUSION: HAART improved survival and
      decreased tuberculosis incidence to a level similar to that achieved in the
      developed countries during the early years of HAART. However, both the mortality
      and the tuberculosis incidence rate were much higher in terms of absolute figures
      in this resource-limited setting. Attention should be paid to the early weeks of
      treatment when mortality is high. The high tuberculosis incidence rate, when
      coupled with the improved survival, may lead to increased tuberculosis
      transmission. This highlights the need for strengthening tuberculosis prevention
      efforts with the scale-up of treatment programmes.

PMID- 16600052
TI  - Mining gene expression data by interpreting principal components.
AB  - BACKGROUND: There are many methods for analyzing microarray data that group
      together genes having similar patterns of expression over all conditions tested.
      However, in many instances the biologically important goal is to identify
      relatively small sets of genes that share coherent expression across only some
      conditions, rather than all or most conditions as required in traditional
      clustering; e.g. genes that are highly up-regulated and/or down-regulated
      similarly across only a subset of conditions. Equally important is the need to
      learn which conditions are the decisive ones in forming such gene sets of
      interest, and how they relate to diverse conditional covariates, such as disease
      diagnosis or prognosis. RESULTS: We present a method for automatically
      identifying such candidate sets of biologically relevant genes using a
      combination of principal components analysis and information theoretic metrics.
      To enable easy use of our methods, we have developed a data analysis package that
      facilitates visualization and subsequent data mining of the independent sources
      of significant variation present in gene microarray expression datasets (or in
      any other similarly structured high-dimensional dataset). We applied these tools
      to two public datasets, and highlight sets of genes most affected by specific
      subsets of conditions (e.g. tissues, treatments, samples, etc.). Statistically
      significant associations for highlighted gene sets were shown via global analysis
      for Gene Ontology term enrichment. Together with covariate associations, the tool
      provides a basis for building testable hypotheses about the biological or
      experimental causes of observed variation. CONCLUSION: We provide an unsupervised
      data mining technique for diverse microarray expression datasets that is distinct
      from major methods now in routine use. In test uses, this method, based on
      publicly available gene annotations, appears to identify numerous sets of
      biologically relevant genes. It has proven especially valuable in instances where
      there are many diverse conditions (10's to hundreds of different tissues or cell
      types), a situation in which many clustering and ordering algorithms become
      problematic. This approach also shows promise in other topic domains such as
      multi-spectral imaging datasets.

PMID- 16600051
TI  - A phylogenomic profile of globins.
AB  - BACKGROUND: Globins occur in all three kingdoms of life: they can be classified
      into single-domain globins and chimeric globins. The latter comprise the
      flavohemoglobins with a C-terminal FAD-binding domain and the gene-regulating
      globin coupled sensors, with variable C-terminal domains. The single-domain
      globins encompass sequences related to chimeric globins and "truncated"
      hemoglobins with a 2-over-2 instead of the canonical 3-over-3 alpha-helical fold.
      RESULTS: A census of globins in 26 archaeal, 245 bacterial and 49 eukaryote
      genomes was carried out. Only approximately 25% of archaea have globins,
      including globin coupled sensors, related single domain globins and 2-over-2
      globins. From one to seven globins per genome were found in approximately 65% of
      the bacterial genomes: the presence and number of globins are positively
      correlated with genome size. Globins appear to be mostly absent in
      Bacteroidetes/Chlorobi, Chlamydia, Lactobacillales, Mollicutes, Rickettsiales,
      Pastorellales and Spirochaetes. Single domain globins occur in metazoans and
      flavohemoglobins are found in fungi, diplomonads and mycetozoans. Although red
      algae have single domain globins, including 2-over-2 globins, the green algae and
      ciliates have only 2-over-2 globins. Plants have symbiotic and nonsymbiotic
      single domain hemoglobins and 2-over-2 hemoglobins. Over 90% of eukaryotes have
      globins: the nematode Caenorhabditis has the most putative globins, approximately
      33. No globins occur in the parasitic, unicellular eukaryotes such as
      Encephalitozoon, Entamoeba, Plasmodium and Trypanosoma. CONCLUSION: Although
      Bacteria have all three types of globins, Archaeado not have flavohemoglobins and
      Eukaryotes lack globin coupled sensors. Since the hemoglobins in organisms other
      than animals are enzymes or sensors, it is likely that the evolution of an oxygen
      transport function accompanied the emergence of multicellular animals.

PMID- 16600053
TI  - The characteristics of the spectra of superior venae cavae in patients with right
      heart failure.
AB  - BACKGROUND: Aimed to elucidate the characteristics of the spectra of superior
      venae cavae (SVC) in respiratory cycles in patients with right heart failure.
      METHODS: The spectra of SVC of 30 patients with right heart failure and 30 paired
      healthy subjects were recorded through right supraclavicular fossa view. The
      profiles of spectra of superior venae cavae were observed, and peak velocity and
      velocity time integral (VTI) of every wave of SVC under spontaneous respiration
      were measured for statistical analysis. RESULTS: In healthy subjects, the peak
      velocities and VTI of S wave and D wave increased in inspiratory phase and
      diminished in expiratory phase, and which of S wave were larger than which of D
      wave in whole respiratory cycle. In patients with right heart failure, spectral
      variations of SVC could be classified into three patterns: Pattern I: peak
      velocities and VTI of S wave were larger than that of D wave in early inspiratory
      phase, but peak velocities and VTI of D wave were larger than those of S wave in
      late inspiratory phase and early expiratory phase [Pattern I-1], even in whole
      respiratory cycle [Pattern I-2]; Pattern II: the S wave disappeared and was
      substituted by inverse wave with low amplitude in whole respiratory cycle.
      Pattern III: the profiles of the spectra of SVC in patients were similar to those
      of healthy subjects. In the whole, the respiratory variation ratios of peak
      velocities and VTI of S wave and D wave were diminished in patients compared with
      those in healthy subjects. CONCLUSION: The spectra of superior venae cavae in
      patients with right heart failure were abnormal, and these characteristics could
      be used as signs in evaluating right heart failure.

PMID- 16600054
TI  - Transduction of biochemical signals across cell membranes.
AB  - Biological cells need to be responsive to various stimuli, primarily chemical
      ligands from their environments. Specific receptor molecules embedded in the
      plasma membrane detect the different biochemical signals that impact the cell,
      and these receptors are the conduits for transmission of this information to the
      cell interior for action. There are several classes of signal transduction
      receptors and many specific receptors within each of the major classes. This
      review emphasizes the structural biology of three major classes of transmembrane
      receptors - tyrosine kinase receptors, histidine kinase sensors, and G-protein
      coupled receptors. Biophysical principles that govern the processes of signal
      transduction across cell membranes are also discussed.

PMID- 16600055
TI  - Addressing the challenges of cellular delivery and bioavailability of peptide
      nucleic acids (PNA).
AB  - Recent results on the cellular delivery of antisense peptide nucleic acids (PNA)
      via peptide conjugation is briefly discussed, in particular in the context of
      endosomal entrapment and escape.

PMID- 16600056
TI  - Lipid microdomains in model and biological membranes: how strong are the
      connections?
AB  - The concept of 'lipid rafts' and related liquid-ordered membrane microdomains has
      attracted great attention in the field of membrane biology, both as a novel
      paradigm in models of membrane organization and for the potential importance of
      such domains in phenomena such as membrane signaling and the differential
      trafficking of various membrane components. Studies of biological and of model
      membranes have gone hand in hand in shaping our current picture of the possible
      organization and functions of liquid-ordered lipid microdomains in membranes.
      This essay discusses some important current questions concerning the existence
      and functional importance of lipid microdomains in mammalian cell membranes, and
      the potential as well as the limitations of using model systems to help to
      address such questions.

PMID- 16600057
TI  - Frightened, threatening, and dissociative parental behavior in low-risk samples:
      description, discussion, and interpretations.
AB  - In 1990 we advanced the hypothesis that frightened and frightening (FR) parental
      behavior would prove to be linked to both unresolved (U) adult attachment status
      as identified in the Adult Attachment Interview and to infant
      disorganized/disoriented (D) attachment as assessed in the Ainsworth Strange
      Situation. Here, we present a coding system for identifying and scoring the
      intensity of the three primary forms of FR behavior (frightened, threatening, and
      dissociative) as well as three subsidiary forms. We review why each primary form
      may induce fear of the parent (the infant's primary "haven of safety"), placing
      the infant in a disorganizing approach-flight paradox. We suggest that, being
      linked to the parent's own unintegrated traumatic experiences (often loss or
      maltreatment), FR behaviors themselves are often guided by parental fright, and
      parallel the three "classic" mammalian responses to fright: flight, attack, and
      freezing behavior. Recent studies of U to FR, as well as FR to D relations are
      presented, including findings regarding AMBIANCE/FR+. Links between dissociation,
      FR, U, and D are explored. Parallel processing and working memory are discussed
      as they relate to these phenomena.

PMID- 16600058
TI  - Examining the role of parental frightened/frightening subtypes in predicting
      disorganized attachment within a brief observational procedure.
AB  - Following Main and Hesse's hypothesis, several investigators have affirmed that
      frightened/frightening (FR) as well as particular atypical maternal behaviors are
      associated with infant disorganized and adult unresolved attachment. Here, for
      the first time, FR behavior was observed in (a) middle-class father-infant (n =
      25) and independent mother-infant dyads (n = 50) and (b) a brief laboratory play
      session. In addition, relations between disorganization, unresolved attachment,
      and the six FR system subscales were explored. Paternal and maternal overall FR
      behavior was related to infant disorganization (n = 75, phi = .61, p < .001), and
      for a subsample where Adult Attachment Interviews were available (n = 32), to
      unresolved adult attachment (phi = .59, p < .001). At the subscale level,
      disorganized-FR behaviors were related to infant disorganization, but only for
      mother-infant dyads. Across the whole sample, both dissociative-FR and
      threatening-FR subscales were associated with infant disorganization. The
      dissociative-FR subscale emerged as the central predictor of infant
      disorganization and was the only subscale significantly related to unresolved
      attachment. The appearance of FR behavior in this 18-min play procedure suggests
      that FR probably occurs more frequently than previously suspected. The possible
      role of dissociative processes in unresolved adult attachment, disorganized
      attachment, and FR parental behavior is discussed.

PMID- 16600059
TI  - Does expectant mothers' unresolved trauma predict frightened/frightening maternal
      behavior? Risk and protective factors.
AB  - This prospective, longitudinal study explored the relationship between mothers
      unresolved/disorganized (U/d) attachment status and frightened/frightening (FR)
      maternal behavior and investigated possible variations due to whether mothers
      were U/d for loss versus abuse. The role of other factors that might predict
      maternal FR behavior was also examined. Pregnant women (n = 116) were
      administered the Adult Attachment Interview and later observed at home for 30-40
      min interacting with their first-born 8-month-olds. Women classified as U/d with
      respect to loss and/or abuse displayed substantially higher levels of FR behavior
      with their infants than did mothers who were not classified as U/d (i.e.,
      secure/autonomous, dismissing, or preoccupied), but these groups did not differ
      on maternal sensitivity. Mothers classified as U/d who had a secondary
      secure/autonomous classification also showed FR behavior but at low levels than
      U/d-insecure mothers. Independent of U/d status, mothers who had lost a parent,
      versus those who did not, more often displayed FR behavior with their infants.
      Finally, U/d loss fully mediated the association between loss of an attachment
      figure other than the parent and FR behavior, and partially mediated the
      relationship between loss of a parent and FR behavior.

PMID- 16600060
TI  - Growth in stature and head circumference in high-functioning autism and Asperger
      disorder during the first 3 years of life.
AB  - Little effort has been made to characterize the developmental anatomic phenotype
      of autism; although there is evidence of an increased head circumference and
      brain size, few other physical characteristics have been studied. The head
      circumference, body length/height, and weight measurements of infants, who were
      later diagnosed with high-functioning autism (HFA, n = 16) and Asperger disorder
      (AsD, n = 12), were extracted from health records over the first 3 years of life
      and compared to the measurements of a matched normal control group (n = 19).
      Using linear mixed-effects models, no differences were found in the average
      growth rate for head circumference, stature, or weight between the children with
      HFA and AsD. However, a significantly higher growth rate in body length/height
      and weight was found for the combined group of children with HFA and AsD compared
      to the normal control group. A trend toward higher growth rate in head
      circumference was also found among the former group. The results indicate that
      growth dysregulation in autism is not specific to the brain but also involves
      growth in stature.

PMID- 16600061
TI  - Positive emotionality at age 3 predicts cognitive styles in 7-year-old children.
AB  - This study examined associations between temperament at age 3 and depressotypic
      cognitive styles at age 7 in a community sample of children. Sixty-four preschool
      aged children were assessed for positive emotionality (PE) and negative
      emotionality (NE) using a standardized battery of laboratory tasks and
      naturalistic home observations. At follow-up 4 years later, the children
      completed laboratory tasks designed to tap helplessness in social and problem
      solving situations, positive and negative information-processing biases, and self
      reports of attributional style. Lower PE at age 3 predicted greater helplessness
      in the interpersonal task and decreased positive schematic processing. There was
      little evidence for a relationship between NE and depressotypic cognitive styles.
      Our findings are consistent with the hypothesis that some portion of cognitive
      vulnerability to depression may stem from early-emerging differences in the
      expression of positive emotions.

PMID- 16600062
TI  - Attachment and behavior problems in middle childhood as reported by adult and
      child informants.
AB  - The predictive relation between attachment and mother, teacher, and self-reported
      psychopathology was examined for a diverse socioeconomic status French Canadian
      sample of 96 children. Attachment classifications were assigned on the basis of
      reunion behavior with mother when the children were approximately 6 years old,
      and child problem behavior was assessed 2 years later using the Child Behavior
      Checklist (mother report), the Social Behavior Questionaire (teacher report), and
      the Dominic Questionnaire (child self-report). Results indicated that both
      insecure/ambivalent and insecure/controlling children children were rated higher
      than secure children on a composite measure of externalizing problems. Concerning
      internalizing problems, only the controlling group was significantly higher on
      both a composite adult (teacher and mother) and self-report measure of
      internalizing problems. Analyses of clinical cutoff scores showed that only the
      controlling group had a significantly greater likelihood of overall problem
      behavior than other children.

PMID- 16600063
TI  - Children's coping strategies and coping efficacy: relations to parent
      socialization, child adjustment, and familial alcoholism.
AB  - The relations of children's coping strategies and coping efficacy to parent
      socialization and child adjustment were examined in a sample of school-age
      children that included families in which some of the grandparents and/or parents
      had an alcoholism diagnosis. Parents and older children reported on the
      children's coping strategies; parents reported on their parenting behavior; and
      teachers reported on children's externalizing and internalizing problems.
      Measures of parent socialization were associated with parents' and children's
      reports of active coping strategies and parents' reports of both support-seeking
      coping and coping efficacy. Some of these relations were moderated by familial
      alcohol status. Children higher in parent-reported active/support-seeking coping
      and coping efficacy were rated lower in teacher-reported externalizing and
      internalizing adjustment problems. The findings were consistent with the view
      that active/support-seeking coping and coping efficacy mediated the association
      of parent socialization to children's psychological adjustment and that this
      relation was sometimes moderated by parental alcohol status.

PMID- 16600065
TI  - Socioemotional development in adolescents at risk for depression: the role of
      maternal depression and attachment style.
AB  - We examined the impact on adolescent socioemotional functioning of maternal
      postnatal depression (PND) and attachment style. We also investigated the role of
      earlier aspects of the child's development-attachment in infancy, and 5-year
      representations of family relationships. Ninety-one mother-child pairs, recruited
      in the postnatal period, were followed up at 13 years. Adolescents were
      interviewed about their friendships, and their level of emotional sensitivity and
      maturity were rated. Emotional sensitivity was heightened in girls whose mothers
      experienced PND; notably, its occurrence was also linked to insecure attachment
      in infancy and raised awareness of emotional components of family relationships
      at 5 years. High emotional sensitivity was also associated with adolescent
      depressed mood. Raised social maturity was predicted by a secure maternal
      attachment style and, for girls, by exposure to maternal PND. Precursors of
      adolescent social maturity were evident in the narrative coherence of 5-year
      family representations. Higher social maturity in the friendship interview was
      also associated with overall good adjustment.

PMID- 16600064
TI  - The impact of classroom aggression on the development of aggressive behavior
      problems in children.
AB  - Prior research suggests that exposure to elementary classrooms characterized by
      high levels of student aggression may contribute to the development of child
      aggressive behavior problems. To explore this process in more detail, this study
      followed a longitudinal sample of 4,907 children and examined demographic factors
      associated with exposure to high-aggression classrooms, including school context
      factors (school size, student poverty levels, and rural vs. urban location) and
      child ethnicity (African American, European American). The developmental impact
      of different temporal patterns of exposure (e.g., primacy, recency, chronicity)
      to high-aggression classrooms was evaluated on child aggression. Analyses
      revealed that African American children attending large, urban schools that
      served socioeconomically disadvantaged students were more likely than other
      students to be exposed to high-aggressive classroom contexts. Hierarchical
      regressions demonstrated cumulative effects for temporal exposure, whereby
      children with multiple years of exposure showed higher levels of aggressive
      behavior after 3 years than children with primacy, less recent, and less chronic
      exposure, controlling for initial levels of aggression. Implications are
      discussed for developmental research and preventive interventions.

PMID- 16600066
TI  - The development and maintenance of anxiety symptoms from infancy through
      adolescence in a longitudinal sample.
AB  - This study examined the etiology and course of anxiety symptoms from infancy
      through adolescence in a longitudinal high-risk community sample. One hundred
      fifty-five subjects were assessed using a variety of observational, projective,
      and objective measures. Results of path analyses revealed the following: (a)
      anxiety symptoms showed moderate stability during childhood and adolescence; (b)
      heightened neonatal biobehavioral reactivity and poor regulation predicted
      emotion regulation difficulties in preschool, which predicted anxiety symptoms in
      childhood; (c) developmental incompetence in childhood predicted anxiety symptoms
      in preadolescence, and anxiety symptoms in preadolescence predicted incompetence
      in adolescence; (d) insecure attachment relationships in infancy predicted
      negative peer relationship representations in preadolescence, and these
      representations predicted anxiety symptoms in adolescence; (e) compared to males,
      females showed similar rates of anxiety symptoms in childhood but greater and
      more stable rates in adolescence; however, males and females showed similar
      patterns of association between risk factors and anxiety symptoms across
      childhood and adolescence; and (f) the model tested was specific in predicting
      anxiety symptoms and not psychopathology in general. The results support a
      developmental model of the etiology and maintenance of anxiety symptoms in
      childhood and highlight factors to consider in efforts to prevent and treat
      childhood anxiety.

PMID- 16600067
TI  - Developmental antecedents of late adolescence substance use patterns.
AB  - This longitudinal study examined antecedents of substance use behavior among 176
      (53% male) adolescents. Adolescents were classified as (a) abstainers (n = 19),
      (b) experimenters (n = 65), (c) at-risk youth (n = 63), and (d) abusers (n = 29)
      based on their reported substance use behavior at age 17.5. Parental behavior,
      peer competence, and problem behavior, measured from early childhood through age
      16, were examined as predictors of substance use patterns. Multinomial logistic
      regression models revealed that early maternal hostility, externalizing behavior
      problems in first grade and at age 16, internalizing behavior in first grade and
      at age 16, and parental monitoring at age 16 significantly differentiated
      substance use groups. The study provides evidence that experiences occurring
      early in development, in addition to those that occur later in development, can
      play a pivotal role in setting the stage for late adolescent substance use
      behavior.

PMID- 16600068
TI  - A prospective high-risk study of the association among maternal negativity,
      apparent frontal lobe dysfunction, and the development of bipolar disorder.
AB  - In a previous paper, the authors found that impairment on the Wisconsin Card
      Sorting Test (WCST) in adolescence was predictive of bipolar disorder in young
      adulthood among offspring of mothers with bipolar illness. In the present study,
      the authors explore the contribution of maternal characteristics, beyond maternal
      mood disorder, to the prediction of offspring dysfunction on the WCST. Results
      showed that maternal bipolar disorder and maternal negativity were both
      predictive of impaired performance on the WCST during adolescence. The
      contribution of maternal negativity to offspring WCST impairment was not better
      explained by maternal personality disorder, mother's functional impairment,
      family loading for bipolar disorder, or offspring disruptive behavioral
      disturbance. Findings did not support a moderator model. However, support was
      found for a mediation model in which maternal negativity contributed to risk for
      offspring bipolar disorder through its negative association with apparent frontal
      lobe functioning, as measured by the WCST. Findings are discussed from the
      perspective of a vulnerability-stress model. In addition, the authors consider
      the possibility that maternal negativity and offspring impairment on the WCST may
      be reflective of a common heritable trait.

PMID- 16600069
TI  - Systemizing empathy: teaching adults with Asperger syndrome or high-functioning
      autism to recognize complex emotions using interactive multimedia.
AB  - This study evaluated Mind Reading, an interactive systematic guide to emotions,
      for its effectiveness in teaching adults with Asperger syndrome (AS) and high
      functioning autism (HFA) to recognize complex emotions in faces and voices.
      Experiment 1 tested a group of adults diagnosed with AS/HFA (n = 19) who used the
      software at home for 10-15 weeks. Participants were tested on recognition of
      faces and voices at three different levels of generalization. A matched control
      group of adults with AS/HFA (n = 22) were assessed without any intervention. In
      addition, a third group of general population controls (n = 24) was tested.
      Experiment 2 repeated the design of Experiment 1 with a group of adults with
      AS/HFA who used the software at home and met in a group with a tutor on a weekly
      basis. They were matched to a control group of adults with AS/HFA attending
      social skills training and to a general population control group (n = 13 for all
      three groups). In both experiments the intervention group improved significantly
      more than the control group on close, but not distant, generalization tasks.
      Verbal IQ had significant effects in Experiment 2. Using Mind Reading for a
      relatively short period of time allows users to learn to recognize a variety of
      complex emotions and mental states. However, additional methods are required to
      enhance generalization.

PMID- 16600070
TI  - Assessing the welfare of genetically altered mice.
AB  - In 2003, under the auspices of the main UK funders of biological and biomedical
      research, a working group was established with a remit to review potential
      welfare issues for genetically altered (GA) mice, to summarize current practice,
      and to recommend contemporary best practice for welfare assessments. The working
      group has produced a report which makes practical recommendations for GA mouse
      welfare assessment and dissemination of welfare information between
      establishments using a 'mouse passport'. The report can be found at
      www.nc3rs.org.uk/GAmice and www.lal.org.uk/gaa and includes templates for the
      recommended welfare assessment scheme and the mouse passport. An overview is
      provided below.

PMID- 16600072
TI  - The electrocardiogram of the Beagle dog: reference values and effect of sex,
      genetic strain, body position and heart rate.
AB  - The aim of the study was to establish a database for electrocardiographic
      parameters of Beagle dogs used for toxicological studies and to evaluate the
      influence of supplier, sex, heart rate (HR) and body position for
      electrocardiogram (ECG) recording on ECG parameters. Peripheral ECG leads were
      recorded from 934 female and 946 male dogs from Marshall Farms and 27 females and
      30 males from Harlan, either standing on a table or restrained in a hammock. HR,
      RR, PQ and QT intervals, P and QRS duration and P-wave amplitude were measured.
      There were no major differences between sexes for ECG parameters. The axis of the
      heart was shifted to the left when the animals were restrained in a hammock
      compared to when they were standing on a table. The PQ interval was higher (about
      9%) in Harlan than in Marshall dogs. HR was negatively correlated with QT
      (coefficient of linear correlation: r=-0.61 to -0.74), which emphasizes the need
      for a formula correcting QT interval for HR when interpreting changes in QT
      interval. HR was also negatively correlated with PQ intervals (r=-0.26 to -0.11),
      whereas a positive correlation was found between HR and the amplitude of the P
      wave (r=0.21-0.34). The level of the respiratory sinus arrhythmia (SA) was
      quantified by calculating the ratio of maximum to minimum RR interval measured
      over a 10 s period. This ratio was negatively correlated with HR (r =-0.49 to 
      0.33). Therefore, at high HRs, SA was less marked than at low HRs, but it did not
      completely disappear. Analysis of beat-to-beat variation indicated that QT and PQ
      intervals and the amplitude of P wave fluctuated over time and the degree of this
      variability was positively correlated with the level of SA. In conclusion, we
      have established reference values for the duration and/or amplitude of some ECG
      parameters both in terms of means and variability over the recording period, and
      we have evaluated the influence of body position, genetic strain and HR on the
      ECG parameters. These data can be used as baseline for the interpretation of the
      ECG of Beagle dogs.

PMID- 16600071
TI  - Review of successful treatment for Helicobacter species in laboratory mice.
AB  - Three variations of the amoxycillin-based triple therapy (amoxycillin,
      metronidazole and bismuth) were administered in the diet, by oral gavage or in
      the diet in conjunction with cross-fostering on to Helicobacter-free foster
      mothers to mice naturally infected with H. hepaticus and/or H. bilis. The
      presence of Helicobacter species was determined by polymerase chain reaction
      (PCR) analysis of faecal pellets. Helicobacter infection was eliminated in 50% of
      strains of mice treated by oral gavage; 57% of strains of mice treated by
      medicated diet alone and 100% of strains of mice treated with the medicated diet
      in conjunction with cross-fostering on to Helicobacter-free foster mothers. Eight
      strains of mice were successfully treated for Helicobacter infection over a two
      year period. The mouse colony has been maintained Helicobacter free, as
      determined by PCR analysis and has remained off treatment from December 2002 to
      March 2005.

PMID- 16600073
TI  - Prevalence of naturally occurring viral infections, Mycoplasma pulmonis and
      Clostridium piliforme in laboratory rodents in Western Europe screened from 2000
      to 2003.
AB  - In this report prevalence rates of rodent viruses in laboratory animals are
      presented based on routine serological screening of mouse and rat colonies from
      European institutes. The prevalences found during the period 2000-2003 are
      compared with those reported for 1981-1984 and 1990-1993. It is shown that some
      infections were eliminated from laboratory animal colonies (e.g. K-virus and
      polyomavirus) by taking preventative measures whereas other infections such as
      mouse hepatitis virus and parvoviruses remained at a high rate. Further decreases
      in prevalence rates in the last 10 years were found for infections such as
      pneumonia virus of mice, reovirus type 3, Sendai virus, sialodacryoadenitis/rat
      coronavirus and Mycoplasma pulmonis. The introduction of new detection methods
      showed that mouse parvovirus and rat parvovirus, both members of the Parvoviridae
      family, remain a major threat to laboratory mice and rats. Guinea pig
      cytomegalovirus and para-influenza virus appeared to be the most prevalent agents
      among laboratory guinea pigs. The importance of a standardized, up-to-date
      screening programme is discussed.

PMID- 16600074
TI  - Antemortem detection of mouse parvovirus and mice minute virus by polymerase
      chain reaction (PCR) of faecal samples.
AB  - Parvoviruses remain one of the most common viral infections seen in laboratory
      mouse colonies. The purpose of this study was to develop an antemortem polymerase
      chain reaction (PCR) assay to detect mice infected with mouse parvovirus-1 (MPV)
      and mice minute virus (MMV) using faecal samples. The MMV PCR assay consistently
      detected as few as 100 plasmid copies of MMV in faecal samples, while the MPV PCR
      assay detected as few as 10 plasmid copies of MPV. Faecal pellets from infected
      mice held at room temperature from 1 to 7 days tested positive by MMV and MPV
      PCR, respectively. This demonstrates that parvovirus DNA is stable in faecal
      samples kept at room temperature. PCR assays were also used to follow the length
      of MMV and MPV shedding in faeces from SENCAR mice, which were endemically
      infected with multiple agents. MMV faecal shedding was detected in 60-70% of the
      mice 5-7 weeks old, and by 13 weeks of age, faecal samples from all mice were
      negative for MMV. MPV faecal shedding was detected in 90-100% of the mice 5-11
      weeks old; however, by 19 weeks of age, faecal samples from all mice were
      negative for MPV. These findings confirm that faecal shedding occurs for a
      limited time and suggest that 5-9-week-old mice are the most appropriate age
      group in endemically infected mice for faecal testing by MMV and MPV PCR.

PMID- 16600075
TI  - Cardiac troponin I is a sensitive, specific biomarker of cardiac injury in
      laboratory animals.
AB  - This study directly demonstrates that cardiac troponin I (cTnI) is a sensitive,
      specific, and persistent biomarker in laboratory animals. Histopathological and
      pathophysiological cardiac changes in dogs, rats and mice correlated with
      increased serum cTnI with various cardiac inotropic agents, and cardiotoxic drugs
      and with cardiac arrhythmias, tachycardia, cardiac effusion with dyspnoea, and
      ageing. A comparison of six immunoassays for cTnI and cardiac troponin T (cTnT)
      to detect and monitor cardiac injury in a rodent model indicated that enzyme
      linked immunosorbent (Life Diagnostics Inc and TriChem Resources Inc, West
      Chester, Philadelphia, USA) and Immulite (Diagnostic Products Corporation,
      Llanberis, UK) assays had low sensitivity and less than 1% of the dynamic range
      of Centaur (Bayer Healthcare Diagnostics, Newbury, UK) cTnI and Elecsys (Roche
      Diagnostics, Basel, Switzerland) and M8 (Bioveris Europe, Whitney, UK) cTnT
      assays. In dogs, however, the Immulite assay was effective and correlated with
      the Centaur. Serum concentrations were highly correlated but 10-fold lower for
      cTnT compared with cTnI with cardiac injury. Centaur assay also detected cTnI in
      myocardium from marmosets, swine, cattle, and guinea pigs, indicating it to be
      candidate cardiac biomarker for these species as well. Purified rat cTnI was 50%
      more reactive than purified human cTnI in the Centaur assay. In the rat, an age-
      and gender-dependent variation in serum cTnI was found. Male rats aged six and
      eight months had a 10-fold greater serum cTnI than age-matched females and three
      month-old rats. These increases correlated with minimal histopathological change.
      Isoproterenol-induced serum cTnI increased up to 760-fold the minimal detectable
      concentration of 0.07 microg/L, within 4-6 h and decreased with a half-life of 6
      h, with an expected return to baseline of 60 h. Severity of histopathological
      change correlated with serum cTnI during the ongoing injury.

PMID- 16600076
TI  - Role of TNF-alpha in prenatal alterations in dams of mice under thermal stress.
AB  - The possible involvement of cytokines such as tumour necrosis factor-alpha (TNF
      alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) that are
      suspected of causing pregnancy loss and miscarriage has been investigated in dams
      of mice subjected to hyperthermia. Thermal stress was induced by exposing mice
      dams at 40+/-2 degrees C for 4 h every day during the different phases of the
      gestation period whereas the normothermic animals were housed at 22+/-2 degrees
      C. The effect of maternal thermal stress was measured in pregnant mice at
      different phases of the gestation period namely, blastogenesis-implantation phase
      (days 0-5 postconceptionem [p.c.]), organogenesis or embryogenesis phase (days 6
      15 p.c.) and fetogenesis phase (days 16-20 p.c.). Uterine examination of dams
      subjected to hyperthermia on days 6-15 p.c. showed maximum reduction in live
      fetus number, gestational index and maximum pre and postimplantation loss in
      comparison with dams housed in normothermic environment and dams exposed to
      thermal stress between days 0-5 and 16-20 p.c. Maximum resorption rate and number
      of non-viable fetuses were observed in dams exposed to hyperthermia during days 6
      15 p.c. Elevated levels of TNF-alpha and IL-1 beta were observed in the amniotic
      fluid of dams subjected to hyperthermia during days 6-15 p.c. but IFN-gamma
      levels remained unaltered. Single intraperitoneal (i.p.) administration of
      recombinant mouse TNF-alpha at a dose of 1 and 0.5 ng/mice in dams on day 6 in
      normothermic condition resulted in a reduced number of live fetuses.
      Administration of anti-TNF-alpha antibody i.p. at a dose of 10 microg/dam on day
      6 p.c. and subjected to thermal stress between days 6-15 p.c. increased
      marginally the number of fetuses but failed to attain statistical significance in
      comparison with days 6-15 p.c. thermally stressed dams without antibody
      treatment. It is concluded that the induction of TNF-alpha, in the amniotic fluid
      is associated with thermal stress during pregnancy and may be linked to the
      reproductive performances of dams. This study will help in understanding the
      mechanism of thermal injury in pregnant subjects.

PMID- 16600077
TI  - Fear conditioning and shock intensity: the choice between minimizing the stress
      induced and reducing the number of animals used.
AB  - Many fear conditioning studies use electric shock as the aversive stimulus. The
      intensity of shocks varies throughout the literature. In this study, shock
      intensities ranging from 0 to 1.5 mA were used, and the effects on the rats
      assessed by both behavioural and biochemical stress parameters. Results indicated
      a significant difference with respect to defaecation and freezing behaviour
      between controls and those animals that received a shock. Significant differences
      in corticosterone levels were also noted between controls and those groups that
      received a shock. No significant differences were found between the shock groups
      with regards to the stress parameters measured in our fear conditioning paradigm,
      indicating that the two shock groups were similarly stressed. Increased
      significance levels were noted for freezing behaviour as well as a lower standard
      error of means was found in the highest shock intensity group. We therefore
      recommend using the higher shock intensity (1.5 mA) as the rats in the higher
      shock intensity group were more homogeneously fear-conditioned and therefore the
      results should be more reproducible and robust than in the lower shock intensity
      group. This would allow for fewer rats to be used in order to gain an accurate
      impression of the conditioning paradigm employed.

PMID- 16600078
TI  - Stress-induced hyperthermia in the rat: comparison of classical and novel
      recording methods.
AB  - Stress causes a rise in body temperature in laboratory animals (stress-induced
      hyperthermia). However, the direct effect of common stressors in animal research,
      i.e. transportation between holding and test rooms or isolation of animals, on
      body temperature has not been investigated to its full extent. To address this
      question, it is important to have a reliable and simple monitoring technique,
      which does not induce stress itself. In the present study, we investigated stress
      related changes in body temperature of F344/Hw rats after (1) moving the cage
      within the holding room, (2) moving the cage from the holding room to another
      test room and (3) social deprivation (isolation). A combination of two different
      body temperature recording methods was used to clarify their accuracy and stress
      inductive character: rectal temperature recording and peritoneal implanted
      temperature sensors (Thermochron iButtons).The results demonstrate that (1)
      different stressors induce a significant rise in body temperature, (2) which is
      detectable for more than 60 min and (3) it is of importance to standardize
      temperature recording methods in order to avoid confounding effects of the
      recording method itself. Furthermore, Thermochron iButtons are more accurate and
      reliable for body temperature studies than rectal recordings.

PMID- 16600079
TI  - Evaluation of antigen panels for ELISA monitoring of mouse colonies for
      antibodies to Pasteurellaceae.
AB  - Pasteurellaceae infection in mice may be monitored by the detection of serum
      antibody using enzyme-linked immunosorbent assay (ELISA). We re-evaluated our
      standard antigen panel comprising Pasteurella pneumotropica and a V-factor
      requiring Haemophilus species (strain H21) by studying their serological
      relationship with Actinobacillus muris and 'Haemophilus influenzae-murium'.
      Serologically, A. muris and 'H. influenzae-murium' were found to be unrelated and
      to differ from P. pneumotropica and Haemophilus strain H21. These four antigens
      were used for monitoring breeding and experimental mouse colonies for a period of
      four years. The addition of 'H. influenzae-murium' antigen to the standard panel
      of antigens significantly increased the proportion of sera and serum panels
      showing anti-Pasteurellaceae antibody activity, but the addition of A. muris
      antigen did not.

PMID- 16600080
TI  - Isoflurane leakage from non-rebreathing rodent anaesthesia circuits: comparison
      of emissions from conventional and modified ports.
AB  - Chronic exposure to low levels of fluorocarbon-based waste anaesthetic gas (WAG)
      has been linked to a multitude of human health problems. We have shown that
      isoflurane exhaust from passive gas-scavenging canisters is often quite high when
      using conventional rodent anaesthesia protocols and equipment. Another likely
      source of WAG build-up in rodent procedure rooms is leakage at the interface
      between the breathing circuit and the animal's face. We evaluated this
      possibility using three non-rebreathing circuits: traditional Bain, modified
      Bain, and Mapleson (type E). For the Mapleson E circuit, a conical rodent
      facemask was attached and used in one of two configurations: normal aperture, or
      aperture modified with a latex diaphragm (cut from an unpowdered surgical glove)
      to reduce the orifice diameter and tighten the seal. Adult female Sprague-Dawley
      rats were anaesthetized with isoflurane (5% for induction, 2% or 3.5% for
      maintenance) in oxygen (2 L/min for induction, 1 L/min for maintenance).
      Isoflurane leakage was assessed by real-time spectrophotometry. In 94% of the
      trials, three configurations - traditional Bain, modified Bain, and Mapleson E
      with unmodified mask - permitted isoflurane leakage approaching or exceeding 100
      ppm at the face/port interface. In contrast, the Mapleson circuit with diaphragm
      modified mask emitted significantly (P<or=0.0003) less isoflurane (peak of 9.5+/
      1.7 ppm [mean+/-standard error]). These data indicate that (1) WAG leakage from
      standard rodent non-rebreathing circuits is substantial, and that (2) a simple,
      rapid, and economical modification to a conventional rodent facemask can
      significantly reduce WAG exposure to workers performing many rodent anaesthesia
      procedures in one session.

PMID- 16600081
TI  - Efficacy of selamectin against mites (Myobia musculi, Mycoptes musculinus and
      Radfordia ensifera) and nematodes (Aspiculuris tetraptera and Syphacia obvelata)
      in mice.
AB  - The effects of selamectin were studied in mice naturally infected with the mites
      Myobia musculi, Myoceptes musculinus and Radfordia ensifera and with the oxyurid
      nematodes Aspiculuris tetraptera and Syphacia obvelata. The mice were divided
      into three treated and three control groups (n=9). Selamectin in the range 10
      12.4 mg/kg was applied topically to the skin in a single spot at the base of the
      neck in front of the scapulae. The mice of treated and control groups were
      necropsied on the 4th, 7th and 21st day after the treatment. While selamectin was
      100% effective in removing M. musculi, M. musculinus and R. ensifera by the
      seventh day, its effect against S. obvelata and A. tetraptera was 36.7% and
      49.2%, respectively on the 21st day.

PMID- 16600082
TI  - Classifying and grading retinal signs in severe malaria.

PMID- 16600083
TI  - [Evaluation for risk of health effect on cadmium exposure].

PMID- 16600084
TI  - [The effects of cadmium on the levels of insulin in smelters].
AB  - OBJECTIVE: To investigate the effects of cadmium on the levels of insulin and
      blood glucose in exposed workers. METHODS: Ninety-eight cadmium-exposed workers
      in a smeltery in the mid-south district of our country were selected as the
      exposed subjects while the healthy doctors in the workers hospital who were not
      exposed to the cadmium were treated as the control. The subjects were grouped
      according to the exposure time, the blood cadmium and the urine cadmium. The
      variety of the level of serum insulin was investigated for the workers in
      different groups of the exposure time, the blood cadmium and the urine cadmium.
      The variety of the levels of the blood zinc and urine zinc were also determined.
      The relationships among the blood cadmium, the blood zinc and the serum insulin
      were analyzed. RESULTS: The level of blood glucose in the group of the exposure
      time of more than 20 years [(4.9 +/- 0.6) mmol/L] was significantly higher than
      that in the control group [(4.6 +/- 0.60) mmol/L] with significantly statistical
      difference (P < 0.01). The level of serum insulin in the group of the exposure
      time of more than 10 years [(8.58 +/- 4.91) microIU/ml] was significantly lower
      than that in the control group [(11.57 +/- 5.42) microIU] with the significantly
      statistical difference (P < 0.05) and the level of serum insulin would be
      decreased significantly with the increase of the blood cadmium and urinary
      cadmium. The level of the urine zinc was increased significantly in the workers
      of the exposure time of more than 20 years. The correlation analysis indicated
      that the negative correlation was found between the level of serum insulin and
      the level of blood cadmium, as well as between the level of the serum insulin and
      the level of the urinary cadmium; the positive correlation was found between the
      level of blood glucose and the level of insulin, as well as between the level of
      blood glucose and the level of C peptide in serum. CONCLUSION: The exposure to
      cadmium can cause the decrease of serum insulin and may affect the level of blood
      glucose.

PMID- 16600085
TI  - [Relationship between plasma anti-metallothionein antibody and renal dysfunction
      in cadmium exposed workers].
AB  - OBJECTIVE: To investigate whether renal dysfunction induced by cadmium is related
      to plasma anti-metallothionein antibody (anti-MT Ab) in workers occupationally
      exposed to cadmium. METHODS: The male workers in a smeltery were selected as the
      subjects for the exposure and effect assessment. The urine cadmium (UCd), the
      blood cadmium (BCd) and the occupational cadmium intake (TTCd) served as the
      exposure indexes while the urine beta(2) microglobulin (Ubeta(2)-MG), the N
      acetyl-beta-D-glucosaminidase (UNAG) and the urine albumin concentration (UALB)
      served as the effect markers for the renal dysfunction caused by the cadmium. The
      titer of the plasma anti-metallothionein antibody was determined with the enzyme
      linked immunosorbent assay (ELISA). RESULTS: The UCd (3.16 microg/g Cr), BCd
      (9.28 microg/L), Ubeta(2)-MG (81.17 microg/g Cr) and UALB (7.03 mg/g Cr) in the
      occupational cadmium exposure group were significantly higher than those in the
      control group and the Ubeta(2)-MG, UNAG and UALB as well as the occurrence rate
      of abnormality would be increased with the increase of the level of the
      occupational cadmium exposure. There was no significant difference in the titer
      of anti-MT Ab between the exposure group and the control group (P > 0.05). The
      titer of the anti-MT Ab would not be increased with the increase of the dosage of
      the exposure and had no significant correlation with BCd, UCd and TTCd (P >
      0.05). The positive correlation were found between anti-MT Ab and UNAG as well as
      between anti-MT Ab and Ubeta(2)-MG in the exposure group with the correlation
      coefficient of 0.302 and 0.218 respectively. The workers with high level anti-MT
      Ab are more susceptible to cadmium nephrotoxicity than those with low anti-MT Ab
      with the odds ratio (OR) value of 4.200 and the 95% CI between 1.213 and 14.541
      (P < 0.05). CONCLUSION: There is a dose-effect relationship between cadmium
      exposure and renal dysfunction in workers occupationally exposed to cadmium, but
      no correlation is found between cadmium exposure and plasma anti-MT Ab. The
      workers occupationally exposed to the cadmium with higher level of anti-MT Ab are
      easier to suffer from renal dysfunction caused by cadmium. Plasma anti-MT Ab
      could be used as a biomarker of susceptibility in the workers exposed to cadmium.

PMID- 16600086
TI  - [Application of metallothionein gene isoforms expression as biomarkers in cadmium
      exposure].
AB  - OBJECTIVE: To investigate the feasibility of metallothionein (MT) gene expression
      level in human peripheral blood lymphocytes (HPBLs) as a biomarker in cadmium
      exposure. METHODS: The MT gene expression level in HPBLs of workers exposed to
      cadmium was examined using RT-PCR technique, and the exposure assessment and
      effect assessment were conducted in exposed workers. RESULTS: The basal MT-1A,
      IE, IF, IX and MT-2A expression level in workers exposed to cadmium were
      significantly higher than those in the control group (P < 0.05). The basal MT-1A,
      IE, IF, IX and MT-2A expression level would be significantly increased with the
      increase of the blood cadmium (BCd) level (P < 0.05). There was a trend of
      increase for the mRNA expression of the basal MT-1A, 1E, IF, IX, MT-2A,
      especially for the mRNA expression of MT-1A and MT-2A (P < 0.05) with the
      increase of the level of the urine cadmium (UCd). There was a good dose-response
      relationship between basal MT-1A expression and UCd. The basal MT-1A, IE, IF, IX
      and MT-2A expression level were significantly correlated with BCd (P < 0.05)
      while the basal MT-1A, IF and MT-2A expression level were significantly
      correlated with UCd (P < 0.05). There were dose-effect relationships of BCd to
      the basal MT-1E, MT-1F, MT-1X and MT-2X expression level respectively and there
      were also dose-effect relationships of UCd, beta(2)-MG and the urine
      metallothionein to the basal MT-1A expression. CONCLUSION: The expression of the
      MT gene isoforms in HPBLs can serve as the biomarker for the cadmium exposure and
      MT-1A can also serve as the effective biomarkers for the cadmium-induced renal
      toxicity.

PMID- 16600087
TI  - [Heme oxygenase-1 expression and apoptosis induced by cadmium in human embryon
      kidney cells].
AB  - OBJECTIVE: To investigate apoptosis and expression of heme oxygenase-1 (HO-1)
      induced by cadmium in human embryonic kidney cells (HEK239T). METHODS: The MTT
      method was used for determining the cell proliferation activity. The apoptosis
      was determined by the flow cytometry. The HO-l mRNA expression and protein level
      were detected by RT-PCR method and Western blot respectively. RESULTS: The ratios
      of apoptosis in HEK239T cells were 11.90% +/- 0.28%, 9.27% +/- 1.73%, 9.79% +/-
      0.67% and 8 .97% +/- 1.60% at the concentration of 5.0, 10.0, 20.0 and 40.0
      micromol/L CdCl(2) respectively, higher than those in the control group (6.69% +/
      0.46%) with the significant difference (P < 0.01). The CdCl(2) of between 10 and
      40 micromol/L could highly induce the expression of HO-1 of the human embryonic
      kidney cells. The expression would increase slowly till the flat stage with the
      increase of the dosage and then would decrease slightly over time. CONCLUSION:
      The cadmium can induce the apoptosis of the human embryonic kidney cells and up
      regulate the expression of HO-1.

PMID- 16600088
TI  - [Application of Benchmark dose (BMD) in estimating biological exposure limit
      (BEL)].
AB  - OBJECTIVE: Based on two sets of data from occupational epidemiology, Benchmark
      dose (BMD) was applied to estimate biological exposure limit (BEL). METHODS:
      Cadmium exposed workers were selected from a cadmium smelting and a zinc products
      factory and control group was selected from doctors or nurses and staff from
      shops living in the same area; Urinary cadmium (UCd) was used as exposure
      biomarker and urinary beta(2) microglobulin (UBM), NAG (UNAG) and albumin (UALB)
      were as effect biomarkers. All urine parameters were adjusted by urinary
      creatinine. Software of BMDS (Version 1.3.2, EPA.U.S) was used to calculate BMD.
      RESULTS: Calculated abnormal prevalence was based on the upper limit of 95% of
      effect biomarkers in control group; There are significant dose response
      relationship between the prevalence of effect biomarkers (UBM, UNAG and UALB) and
      exposure biomarker (UCd); BEL was 5 microg/g creatinine for UBM as effect
      biomarker, It consists with the recommendation of WHO; BEL was 3 microg/g
      creatinine for UNAG as effect biomarker; BEL can be estimated by using the method
      of BMD; the more sensitive biomarker would used, the more occupational people
      would protected. CONCLUSION: The application of BMD in estimating biological
      exposure limit (BEL) is proper. UNAG is suggested as most sensitive biomarker to
      be used to estimate BEL for cadmium exposure.

PMID- 16600090
TI  - [Construction of RNA interference expression vectors of human neuropathy target
      esterase and its inhibition for expression of NTE in mammalian cells].
AB  - OBJECTIVE: To construct the RNA interference expression vector for expression of
      human neuropathy target esterase (NTE) gene in mammalian cells. METHODS: Spe I
      and Xho I-digested insert from pSUPER, which comprised H1 RNA polymerase III
      promoter and the multiple cloning sites, were cloned into the compatible in the
      pcDNA3.1 (+) to generate pSUPER/neo that could express small interfering RNA in
      mammalian cells. The annealed oligos targeting the expression of NTE were ligated
      into pSUPER/neo vector digested with Bgl II and Hind III to generate pSUPER/neo
      NTE, which was transfected into COS7 and SH-SY5Y cells. The inhibitory effect of
      the expression of NTE was detected by western blot analysis and the enzyme
      activity assay. RESULTS: pSUPER/neo-NTE could stably express double-stranded RNA
      of NTE. The expression of pSUPER/neo-NTE in COS7 and SH-SY5Y cells could
      efficiently inhibit the activity of NTE in the mammalian cells. CONCLUSION:
      Stable eukaryotic expression vector of double-stranded RNA of NTE, pSUPER/neo
      NTE, has been constructed successfully with promoter substitution strategy.

PMID- 16600089
TI  - [Application of benchmark dose (BMD) in a bone-effect study on a general
      population environmentally exposed to cadmium].
AB  - OBJECTIVE: To estimate the benchmark dose for osteoporosis caused by cadmium
      exposure in a Chinese general population with an epidemiological study. METHODS:
      The inhabitants living in both cadmium polluted and non-polluted areas served as
      the exposure group and the control group. Urinary cadmium (UCd) and Blood cadmium
      (BCd) were used as exposure biomarkers while the Z score was used as effect
      biomarker for the osteoporosis. RESULTS: The UCd and BCd in the habitants of the
      polluted areas were significantly higher than those in the habitants of the
      control area on average (P < 0.05) and the UCd and BCd in the habitants of the
      highly polluted areas were significantly higher than those in the habitants of
      the moderately polluted area on average (P < 0.05). The bone mineral density was
      significantly decreased in the groups of the highest UCd and BCd level compared
      with the 5 microg/g Cr group with the significant difference (P < 0.05). The
      morbidity of the osteoporosis would increase significantly with the increase of
      the cadmium exposure (P < 0.05) with the linear correlation (P < 0.05). BMDs were
      calculated using BMDS Version l.3.2 software and BMDLs were also determined. The
      BMDL of UCd for cadmium-induced osteoporosis was higher than those representing
      cadmium-induced renal dysfunction. CONCLUSION: High level of cadmium exposure can
      induce osteoporosis, which occurs later than renal damage related to cadmium
      exposure. The BMD is a practical method.

PMID- 16600091
TI  - [Altered systemic iron metabolism in welders exposed to manganese].
AB  - OBJECTIVE: To investigate the systemic changes of iron metabolism following
      manganese exposure. METHODS: Ninety-seven welders and 91 workers with no history
      of exposure to manganese were recruited from the same factory in Beijing serving
      as the exposure group and the control group respectively. The welding rods used
      were type J422. The concentration of the manganese in the air of the work place
      was determined respectively with the national standard method. The serum iron and
      manganese, ferritin, transferrin and transferrin receptors were measured with the
      graphite furnace atomic absorption spectrophotometry and ELISA in both groups.
      RESULTS: The permissible concentration-STEL of ambient Mn in welders' breathing
      zone ranged from 0.53 mg/m(3) to 2.19 mg/m(3), while the permissible
      concentration-TWA of ambient Mn was between 0.29 mg/m(3) and 0.92 mg/m(3) in the
      breathing zone of the workplace. Serum Mn and Fe concentrations in welders were
      about 1.40 times (P < 0.0l) and 1.2 times (P < 0.01), respectively, higher than
      those of control subjects. At the same time, the transferrin concentrations in
      serum were significantly higher (about 1.2 times, P < 0.05) in welders than in
      controls. In contrast, transferrin receptors were significantly lower (about 1.2
      times) in exposed subjects than controls (P = 0.001). There was no difference in
      serum ferritin between the two groups (P = 0.112). Although there was no
      significant trend, the serum ferritin level was increased by 18% in comparison
      with that of the control. The abnormal percentage of serum Fe and Serum Mn in
      welders were 55.67% and 67.01% respectively, higher than those of control
      subjects. In addition, the correlations between all indicators and the duration
      of employment were not observed. CONCLUSION: The long term exposure to the
      manganese can induce the disorder of the iron metabolism, which is found in the
      expression of increase of the serum iron and transferrin as well as the decrease
      of transferrin receptors.

PMID- 16600092
TI  - [Effects of selenium on expression of TERT, c-Myc and p53 induced by cadmium in
      rat liver].
AB  - OBJECTIVE: To study the effects of sodium selenite on expression of telomerase
      reverse transcriptase mRNA, c-Myc and p53 induced by cadmium chloride in rat
      liver. METHODS: Male SD rats were divided randomly into 6 groups, each group had
      5 animals. The groups comprised the control group, Se group (5 micromol/kg sodium
      selenite), 5 micromol/kg cadmium chloride group, 10 micromol/kg cadmium chloride
      group, Se (5 micromol/kg sodium selenite) + 5 micromol/kg cadmium chloride group,
      Se (5 micromol/kg sodium selenite) + 10 micromol/kg cadmium chloride group. After
      48 hours of the first injection, the expression of TERT mRNA was measured with RT
      PCR and c-Myc, and p53 proteins were measured by immunohistochemistry method.
      RESULTS: Compared with control group, the expression of TERT was increased in 5
      micromol/kg Cd group and 10 micromol/kg Cd group, c-Myc protein was increased in
      10 micromol/kg Cd group, and the expression of p53 protein was increased in 5
      micromol/kg group and 10 micromol/kg Cd group. TERT expression in Se + 10
      micromol/kg Cd group was lower than that of 10 micromol/kg Cd group
      significantly. c-Myc protein was decreased in Se + 10 micromol/kg Cd group
      compared with 10 micromol/kg Cd group. p53 protein of Se + 5 micromol/kg Cd group
      and Se + 10 micromol/kg Cd group were decreased significantly compared with 5
      micromol/kg Cd group and 10 micromol/kg Cd group respectively. CONCLUSION: The
      cadmium at the doses of between 5 and 10 micromol/kg can activate TERT and up
      regulate c-Myc and p53 proteins. The selenium at the dose of 5 micromol/kg has
      the antagonistic effect on expression of TERT, c-Myc and p53 induced by cadmium
      in rat liver.

PMID- 16600093
TI  - [Determination of cotinine in human urine with gas chromatograph-mass
      spectrometry].
AB  - OBJECTIVE: To establish the method of gas chromatograph-mass spectrometry (GC-MS)
      for the determination of the cotinine (COT) in human urine. METHODS: The
      conjugated trans-3'-hydroxycotinine (THOC) and COT were hydrolyzed in human urine
      with beta-glucuronidase. The composition of COT was extracted with the mixture of
      dichloromethane and n-butyl acetate (2:1) and was separated with HP-5MS fused
      silica capillary column. The GC-MS was used for determining its content. RESULTS:
      The monitoring limit of this method was 0.02 microg/L. Its recovery rate was
      higher than 90%, Its accuracy rate was 4.30%. It was used for the determination
      of the cotinine in human urine in Guangzhou Biological Bank the Elderly Cohort.
      CONCLUSION: The GC-MS method is a good microanalysis for monitoring the cotinine
      in human urine rapidly and accurately with little background disturbance. It has
      been applied in our Guangzhou Cohort Study for determining cotinine in human
      urine.

PMID- 16600094
TI  - [Expression of cadmium-induced response protein].

PMID- 16600096
TI  - [Determination of serum diaminodiphenyl methane with gas chromatograph-mass
      spectrometry].

PMID- 16600095
TI  - [Several heavy metals and placenta barrier].

PMID- 16600097
TI  - [Determination of 16 trace elements in whole blood with microwave digestion
      inductively coupled plasma mass spectrometry].

PMID- 16600098
TI  - [Determination of plumbum in urine with hydride generation-atomic fluorescence
      spectrometry].

PMID- 16600099
TI  - [Determination of phthalic acid esters in air with capillary gas chromatography].

PMID- 16600100
TI  - [Occupational hazards of AIDS and protection methods].

PMID- 16600102
TI  - [Expression of T cell receptor Vbeta subfamily gene in patients with benzene
      induced aplastic anemia].

PMID- 16600103
TI  - [Emergency treatment for 73 patients with acute tetramethylene-disulfo-tetramine
      poisoning].

PMID- 16600104
TI  - [Two cases of acute irritant gas-induced lung injury].

PMID- 16600105
TI  - [Research of toxicological mechanism and "Omics"].

PMID- 16600106
TI  - [cyclin D1/E2F pathways involved in cell cycle changes of human embryo lung
      fibroblasts induced by benzo(a)pyrene].
AB  - OBJECTIVE: To investigate the roles of cyclin D1/CDK4-E2F-1/4 pathway in cell
      cycle changes of human embryo lung fibroblasts (HELF) induced by two different
      benzo(a)pyrene [B(a)P] treatment models. METHODS: Two B(a)P treatment models:
      HELF were treated by 2 micromol/L B(a)P for 24 hours; HELF were treated by 100
      micromol/L B(a)P three times 24 hours each and provide with some characteristics
      of transformed cells (T-HELF). Changes of cell cycle and the expression of cyclin
      D1, CDK4 and E2F-1/4 were checked using the flow cytometry and Western bolt
      analysis. RESULTS: After 24 hours 2 microml/L B(a)P treatment, the HELFs in the
      G(1) phase was decreased. In HELF transfected with antisense cyclin Dl (A-Dl) and
      antisense CDK4 (A-K4), the expression of cyclin Dl and CDK4 blocked the cell
      cycle changes from the G(1) phase to the S phase induced by B(a)P. The
      overexpression of cyclin Dl and E2F-1 in HELF was induced by B(a)P. The E2F-1
      overexpression in A-D1 induced B(a)P was inhibited. The E2F-4 expression was
      decreased and the CDK4 expression was increased significantly in A-K4 after B(a)P
      treatment. Most of T-HELF transfected with antisense cyclin Dl (T-A-Dl) and
      antisense CDK4 (T-A-K4) were retained in G(1) phase. The cyclin Dl expression in
      T-HELF was increased significantly compared with that in HELF. The E2F-4
      expression in T-A-Dl and T-A-K4 was increased significantly compared with that in
      T-HELF. CONCLUSION: B(a)P induces the cell cycle changes through cyclin D1/CDK4
      E2F-1/4 pathway in HELF treated by 2 micromol/L B(a)P while it induces cell cycle
      changes through cyclin D1/CDK4-E2F-4 pathway in T-HELF.

PMID- 16600107
TI  - [ERK and JNK/AP-1 pathways involved in benzo(a)pyrene induced cell cycle changes
      in human embryo lung fibroblasts].
AB  - OBJECTIVE: To study the role of mitogen activated protein kinase (MAPK)/activator
      protein-1 (AP-1) pathway in benzo(a)pyrene (B(a)P)-induced changes of cell cycle
      in human embryo lung fibroblasts (HELF). METHODS: AP-1 luciferase activity was
      determined by the Luciferase reporter gene assay using a luminometer. The
      expression levels and activity of extracellular signal-regulated protein kinase
      (ERK), c-Jun NH2-terminal kinase (JNK) and p38 were determined by Western blot.
      Flow cytometric analysis was employed to detect the distributions of cell cycle.
      The dominant negative mutant of ERK2, JNK1 and p38 were applied to detect the
      upstream or downstream relationship of signaling pathways. RESULTS: B(a)P
      treatment resulted in a marked activation of AP-1 and its upstream MAPK,
      including ERK, JNK and p38 in human embryo lung fibroblasts (HELF). B(a)P
      exposure also led to increase the population of cells at S phase compared to
      control (P < 0.01) with a concomitant decline of cells at G(1) phase. B(a)P
      induced cell cycle alternation was markedly impaired by stable expression of a
      dominant negative mutant of ERK2 or JNK1, but not p38. B(a)P-induced AP-1
      transactivation was inhibited by the overexpression of dominant-negative mutant
      of ERK2 or JNK1, but not p38. Inhibition of the activation of AP-1 by curcumin, a
      chemical inhibitor of AP-1, significantly inhibited the cell cycle changes in
      response to B(a)P treatment. CONCLUSION: ERK and JNK, but not p38, mediated
      benzo(a)pyrene-induced cell cycle changes by AP-1 transactivation in HELF.

PMID- 16600108
TI  - [Clinical analysis for acute cyanogen chloride inhalation poisoning].

PMID- 16600109
TI  - [p38/ERK signal pathways regulating the expression of type I collagen and
      activity of MMP-2 in TGF-beta1-stimulated HLF-02 cells].
AB  - OBJECTIVE: To investigate the role of TGF-beta(1)/MAPK signaling pathways in the
      expression of type I collagen and activity of MMP-2, 9 in human lung fibroblasts.
      METHODS: Human lung fibroblasts cell line (HLF-02) was cultured and and then
      stimulated with 10 ng/ml TGF-beta(1) for different time; SB203580 or PD98059 was
      added into culture medium to block p38 or ERK kinase pathway before incubated
      with TGF-beta(1); the expression of type I collagen was detected by Western
      blotting and RT-PCR; zymogram analysis was used to analyze the activity of MMP-2
      and MMP-9. RESULTS: (1) In the process of stimulation by TGF-beta(1), the type I
      collagen mRNA level of 24 h, 48 h and 72 h group was: 1.33 +/- 0.07, 2.46 +/-
      0.09 and 2.39 +/- 0.08 respectively; and the type I collagen protein level of 24
      h, 48 h and 72 h group was: 114.89 +/- 8.95, 208.16 +/- 6.75 and 211.46 +/- 8.05
      respectively; and the activity of MMP-2 of 24 h, 48 h and 72 h group was: 190.33
      +/- 5.86, 214.33 +/- 8.39 and 212.67 +/- 11.59 respectively. (2) SB203580
      significantly inhibited the TGF-beta(1)-induced expression of type I collagen
      mRNA, protein and MMP-2 activity (inhibition ratio: 51%, 24% and 20%); (3)
      PD98059 also significantly attenuated the TGF-beta(1)-induced expression of type
      I collagen mRNA, protein and MMP-2 activity (inhibition ratio: 42%, 13% and 16%).
      CONCLUSION: TGF-beta(1) is capable of inducing the expression of type I collagen
      mRNA and protein and up-regulating MMP-2 activity in HLF-02 cells. p38 and ERK
      kinase signaling pathways play important role in regulation and control for this
      process.

PMID- 16600110
TI  - [The cytotoxicity of nickel-refining dusts for chinese hamster lung cells and
      effects on gap junctional intercellular communication].
AB  - OBJECTIVE: To investigate the cytotoxicity of the nickel-refining dusts for
      Chinese hamster lung (CHL) cells and the effects of nickel-refining dusts on the
      gap junctional intercellular communication (GJIC) of CHL cells. METHODS: The
      cytotoxicity of the nickel-refining dusts for the CHL cells was determined in two
      nickel-refining dusts samples with the CHL cells as the target cells by MTT
      method while the effects of nickel-refining dusts on the CJIC of the CHL cells
      were investigated using the scrape-loading and dye transfer (SLDT) technique.
      RESULTS: There were no significant difference in the CHL proliferation between
      all dosage groups in the two samples and the control group at 6 and 12 hours (P >
      0.05). The survival rate of cells in all dosage groups were all decreased at 36
      hours (P < 0.05), presenting the dosage-reaction relationship and the time
      reaction relationship. IC(50) was 21.36 and 23.07 micro/ml for the two samples
      respectively at 36 hours. Compared with the control group, the transport of
      Lucifer Yellow (LY) from the injury line to the adjacent cells was decreased when
      the CHL cells were treated with nickel-refining dusts of 25.00, 50.00 and 100.00
      microg/ml (P < 0.01). CONCLUSION: The nickel-refining dusts have cytotoxicity for
      the CHL cells cultivated in vitro, can inhibit the growth of the cells and at a
      certain concentration can inhibit the GJIC function of CHL cells.

PMID- 16600111
TI  - [Influence of smoke tar on mRNA expression of aromatic hydrocarbon receptor and
      cytochrome P4501A1 gene of mice lungs].
AB  - OBJECTIVE: To investigate the influence of the smoke tar on the expression of
      aromatic hydrocarbon receptor (AHR) and the cytochrome P4501Al (CYP1A1) gene of
      mice lungs. METHODS: The smoke tar of 5.29, 10.58 and 15.87 mg/kg was
      administered intraperitoneally in mice respectively. RNA of mice lungs was got
      with RNA kit. RT-PCR technique was used for determining AHR and CYP1A1 gene
      expression with beta-actin as control. RESULTS: The AHR gene expression level was
      (0.554 +/- 0.023) for the mice intraperitoneally administered with 5.29 mg/kg
      smoke tar for 72 hours with the significant difference in gene expression level
      compared with the Tween-80 group (0.484 +/- 0.045) (P < 0.05). The AHR gene
      expression levels were (0.555 +/- 0.014), (0.606 +/- 0.051), and (0.566 +/-
      0.014), (0.684 +/- 0.069) for the mice intraperitoneally administered with 10.58
      and 15.87 mg/kg smoke tar for 48 hours and 72 hours respectively with the
      significant difference in gene expression level compared with the Tween-80 group
      (0.486 +/- 0.060, 0.484 +/- 0.045) (P < 0.05, P < 0.01). The CYP1Al gene
      expression levels were (1.535 +/- 0.021), (1.643 +/- 0.046) and (1.624 +/-
      0.056), (1.739 +/- 0.038) respectively with the significant difference compared
      with the Tween-80 group (l.436 +/- 0.016, 1.404 +/- 0.036) (P < 0.01).
      CONCLUSION: The smoke tar can regulate up the expression of AHR and CYP1A1 gene
      at a certain dosage and time. The regulation of the smoke tar for the expression
      of AHR was earlier than for that of CYP1A1.

PMID- 16600112
TI  - [Effects of overexpression of human pol-beta on cellular response to DNA damage].
AB  - OBJECTIVE: To investigate the biological effects of overexpression of the human
      DNA polymerase (pol-beta) on cellular response to DNA damage. METHODS: The cell
      strain HLFbeta from the stable overexpression of the human pol-beta was
      contaminated with methyl methanesulfonate (MMS) for investigating the effects of
      the pol-beta on the cellular responses to DNA damage on the aspects such as the
      DNA damage, the cell cycle and the induced mutation rate. RESULTS: The cell
      HLFbeta from the stable overexpression of the human pol-beta was obtained through
      the screening. The cellular response to DNA damage of HLFbeta induced by the MMS
      in the intermediate and high dosage group (ranging from 0.5 to 0.8 mmol/L) was
      significantly lower than that in the control group. The analysis for the cell
      cycle distribution showed that both the two types of cells contaminated by MMS
      had retardation at G(2) phase. In the HLFbeta group, the cells had the obvious
      G(2) phase retardation and 49.0% of the cells were retarded at G(1) phase as well
      when the MMS was increased to 0.5 mmol/L while in the control, only 20.1% of the
      cells were retarded at the G(1) phase when the same dosage of MMS was
      administered. Moreover, the MMS-induced mutagenesis in HLFbeta was increased from
      4.5 x 10(-6) to 8.2 x 10(-6), significantly higher than that in the control group
      (P < 0.05). CONCLUSION: High Pol-beta level decreases cellular DNA damage induced
      by MMS. Nevertheless, the overexpression of Pol-beta can also increase error
      prone DNA synthesis during DNA repair process.

PMID- 16600113
TI  - [p16 and MGMT gene methylation in sputum cells of uranium workers].
AB  - OBJECTIVE: To study the methylation of O-6-methylguanine-DNA methyltransferase
      (MGMT) and p16 gene in the sputum cells of radon-exposed population. To provide
      the experimental base for finding the molecular biomarker of the high risk
      population of the radon-induced lung cancer. METHODS: 91 radon-exposed workers
      were divided into 4 groups, high dosage group (> 120 WLM), middle dosage group
      (between 60 and 120 WLM), low dosage group (between 30 and 60 WLB) and lower
      dosage group (between 2 and 30 WLM) according to the accumulated exposure dosage
      of the radon daughters. The abnormal methylation of p16 and MGMT gene in the
      sputum cells of the population in the four groups was detected with the
      methylation specific PCR (MSP). RESULTS: There was significantly upward trend for
      the p16 gene methylation rate (0.00%-20.00%), the MGMT gene methylation rate
      (0.00%-28.00%) and the total methylation rate (0.00%-40.00%) with the increase of
      the accumulated exposure dosage of the radon daughters (P < 0.01). CONCLUSION:
      The methylation of p16 and MGMT gene is related to the accumulate exposure dosage
      of the radon daughters.

PMID- 16600114
TI  - [Levels and clinic significance of serum soluble Fas and soluble Fas ligand in
      coal workers' pneumoconiosis].
AB  - OBJECTIVE: To investigate the changes of levels and clinic significance of serum
      soluble Fas (sFas) and soluble FasL (sFasL) in coal workers' pneumonoconiosis.
      METHODS: Serum levels of sFas and sFasL were determined in 52 patients with
      silicosis, 57 coal workers' pneumonoconiosis, 46 healthy underground coal
      workers' (the underground control group) and 40 healthy volunteers working on the
      ground (the ground control group) with a sandwich ELISA. RESULTS: Compared to the
      underground control and the ground control group, the serum levels of sFas and
      sFasL in the patients with silicosis and the coal workers' pneumonoconiosis were
      significantly higher (P < 0.01). Serum levels of sFas and sFasL in the
      underground control group were significantly higher than those in the ground
      control group (P < 0.01); Serum sFas levels in coal workers' pneumonoconiosis was
      significantly higher than those in the patients with silicosis (P < 0.01).
      Although the serum sFasL levels was also increased, there was no significant
      difference (P > 0.05). In the patients with silicosis and the coal workers'
      pneumonoconiosis patients, the serum sFas levels in Phase I patients combined
      with emphysema and simple Phase II + III patients were significantly higher than
      those in simple Phase I patients (P < 0.01). There was no significant difference
      in the serum sFasL levels among various groups with different parameters of
      pneumonoconiosis. In the patients with silicosis and the coal workers'
      pneumonoconiosis, serum levels of sFas and sFasL were not significantly altered
      among different duration of exposure to dusts. There was no correlation between
      serum levels of sFas and sFasL in the patients with silicosis while there was a
      slightly positive correlation between sFas and sFasL levels in the coal workers'
      pneumonoconiosis (r = 0.479, P < 0.05). CONCLUSION: In the patients with
      silicosis and the coal workers' pneumonoconiosis, the serum levels of sFas and
      sFasL are abnormal and associated with the development of the pneumonoconiosis.
      The changes of serum sFas levels may indicate the development and progression of
      the pneumonoconiosis. The detection of the serum sFas level may be used in the
      differential diagnosis for the silicosis and the coal worker's pneumonoconiosis.

PMID- 16600115
TI  - [Changes of tight junction and Cx43 expression in microvessel endothelial cells
      of mouse lung induced by bleomycin].
AB  - OBJECTIVE: To investigate the changes of expression of connexin-43 (Cx43) and the
      tight junction of microvessel endothelial cells (EC) to approach the effects in
      bleomycin (BLM) induced pulmonary fibrosis (PF). METHODS: Forty healthy rats were
      equally and randomizedly divided into the control group and the experiment group.
      In both group, vWf in blood serum was measured with ELISA method on 3rd, 7th,
      14th, 28th day after BLM treatment. Rats in each group were infused with
      lanthanum nitrate on 3rd, 7th, 14th, 28th day after BLM treatment. The lung
      samples were made and the tight junction and the distribution of the granules of
      lanthanum in the microvessel EC were observed with transmission electron
      microscopy in the control and experiment groups. The lung microvessel EC of the
      rats in each group were preserved by tissue culture methods at the same time, and
      the expression of Cx43 were observed by laser scanning confocal microscopy.
      RESULTS: The serum vWf in the peripheral blood of the experiment group was
      significantly higher than that of the control group, and was the highest on 3rd
      day after BLM treatment (P < 0.01). The blood vessel EC of the control group were
      intact. The basement membrane was uninterrupted. Granules of lanthanum nitrate
      did not penetrate the tight junction of EC. The width of junction gap in the
      experimental group was increased and the lanthanum granules of high density were
      found deposited in the linear form in the gap junction. Low expression of Cx43
      was observed in experiment group. The expression rate of Cx43 was 25%, 38%, 45%
      and 71% respectively on 3rd, 7th, 14th, 28th day, significantly less than those
      in the control group (P < 0.05). CONCLUSION: It may be the important pathological
      basis for the BLM induced abnormality of the interstitial tissues in the lung
      that the tight junction of EC is continuously in the open state, which causes the
      effusions of inflammatory cells and the corresponding cytokine secretion, and
      thus initiates the overproliferation of fibroblasts.

PMID- 16600116
TI  - [The relationship between hormesis of proliferation and oxidative stress induced
      by sodium arsenite in human embryo lung fibroblasts].
AB  - OBJECTIVE: To investigate the relationship between the hormesis of proliferation
      and oxidative stress induced by sodium arsenite (Na(2)AsO(2)) in human embryo
      lung fibroblasts (HELF). METHODS: HELF were treated with Na(2)AsO(2) of 0.0, 0.1,
      0.5, 1.0, 5.0 and 10.0 micromol/L for 4 hours or 24 hours, respectively. The cell
      proliferation, the reactive oxygen species (ROS) level, the malondialdehyde (MDA)
      content and the activity of glutathione peroxide (GSH-Px) and the superoxide
      dismutase (SOD) in HELF were detected respectively. RESULTS: The HELF
      proliferation induced by 0.1 and 0.5 micromol/L Na(2)AsO(2) was significantly
      higher than that in the control group (P < 0.01). The HELF proliferation induced
      by 5.0 and 10.0 micromol/L Na(2)AsO(2) was significantly lower than that in the
      control group (P < 0.01) with the dose-effect relation of an inverted U curve.
      The ROS level induced by Na(2)AsO(2) of between 0.5 and 10.0 micromol/L was
      significantly increased (P < 0.05, P < 0.01). The positive correlation was found
      between the ROS level and the exposure dose of Na(2)AsO(2) (r = 0.934, P < 0.01).
      The 5.0 and 10.0 micromol/L Na(2)AsO(2) induced the significant increase of the
      MDA contents (P < 0.01) and the significant decrease of the GSH-Px activity
      compared to those in the control group (P < 0.01). The SOD activity in 0.5
      micromol/L Na(2)AsO(2) group was significantly higher than that in the control
      group (P < 0.01) while the SOD activity induced by 5.0 and 10.0 micromol/L
      Na(2)AsO(2) was significantly decreased (P < 0.01) if compared with the control
      group with the dose-effect relation of an inverted U curve. CONCLUSION: The
      sodium arsenite can induce the hormesis of proliferation in HELF with the dose
      effect relation of an inverted U curve. The mechanisms probably relates to
      different levels of oxidative stress induced by sodium arsenite of different
      concentrations.

PMID- 16600117
TI  - [Application of micronucleus test of buccal mucosal cells in assessing the
      genetic damage of workers exposed to acrylonitrile].
AB  - OBJECTIVE: To investigate the application of micronucleus test of buccal mucosal
      cells in monitoring the genetic effect of acrylonitrile in the population exposed
      to the acrylonitrile. METHODS: Forty-one healthy male workers in a chemical
      factory in Shanghai were selected as the low concentration acrylonitrile exposed
      group while forty-seven healthy male workers in an acrylonitrile factory in
      Shanghai were selected as the intermediate concentration acrylonitrile exposed
      group. At the same time, thirty-one male workers who had no toxicant exposure and
      lived in the same community were selected as the control group. The micronucleus
      test in buccal mucosal cells and lymphocytes were used respectively for assessing
      the genetic damage status of these men. RESULTS: The rate of micronucleus in
      buccal mucosal cells in both acrylonitrile groups (the low concentration group:
      3.68% +/- 2.72%; the intermediate concentration group: 4.00% +/- 2.38%) was
      significantly higher than that in the control group (2.03% +/- 2.20%) (P < 0.05).
      The rate of micronucleus in the intermediate concentration group (4.23% +/-
      3.34%) was significantly higher than that in the control group (2.48% +/- 1.46%)
      (P < 0.05). There was the correlation between the micronucleus test of buccal
      mucosal cells and the micronucleus test of the lymphocytes in the peripheral
      blood in the acrylonitrile exposed population (r = 0.299-0.359, P < 0.05).
      CONCLUSION: The micronucleus test of buccal mucosal cells replacing the
      micronucleus test of the lymphocytes in the peripheral blood can be used as one
      of the screening indexes in the surveillance of the genetic damage in the
      acrylonitrile exposed population.

PMID- 16600118
TI  - [The effects of traffic air pollution on pulmonary function of traffic
      policemen].

PMID- 16600119
TI  - [Requirement of refractory material workers for soluble vitamins].

PMID- 16600120
TI  - [Investigation and analysis for morbidity of pneumoconiosis in Meizhou city from
      1987 to 2004].

PMID- 16600121
TI  - [Investigation of morbidity of pneumoconiosis in the rock gold mining peasant
      workers].

PMID- 16600122
TI  - [Study on the acute pulmonary injury in rats induced by nano-SiO2 and standard
      SiO2].

PMID- 16600123
TI  - [Study on pathogenic bacteria in lung infection during mechanical ventilation for
      patients with acute organophosphorus pesticide poisoning].

PMID- 16600124
TI  - [Significance of serum sialic acid and ceruloplasmin in early lung fibrosis of
      pneumoconiosis].

PMID- 16600125
TI  - [Clinical study on injected carbamide peroxide for treatment of respiratory
      failure complicated by lung infection in coal workers' pneumoconiosis].

PMID- 16600126
TI  - [Value of urinary retinal binding protein in early renal function impairment for
      patients with pneumoconiosis complicated with chronic obstructive pulmonary
      diseases].

PMID- 16600127
TI  - [Study on mutations of gyrA gene of tuberculosis quinolone-tolerant isolates in
      coal workers' pneumoconiosis].

PMID- 16600128
TI  - [Review on interleukin-6 and the fibrosis diseases].

PMID- 16600129
TI  - [Relationship between depression symptoms and stress in occupational
      populations].
AB  - OBJECTIVE: To explore the relationship between the depression symptoms and
      occupational stress in occupational populations. METHODS: Depression symptoms
      were measured by using the center for epidemiological survey-depression scale.
      The occupational stress instrument were employed to investigate the stressors,
      personalities, social support, and coping strategies as well as the subject's
      age, length of service, sex, educational level and marriage status. Chi(2) test
      was used for analyzing the difference of depression. The multiple covariance
      analysis was used for testing the difference of stressors, personalities, social
      support, and coping strategies among the groups with different scores of
      depression. The variables obtained in the optional prediction equation were
      identified by multiple stepwise regression analysis. RESULTS: The incidence rate
      of definite depression symptoms was 40.2%. The total average score was 21.74 +/-
      8.99. Henan province had the highest incidence rate of depression symptoms,
      43.8%, Hebei 39.4%, and Beijing the lowest, 23.4%. The male workers had the
      higher incidence rate of depression symptoms, 43. 0% than female, 35.4% (P <
      0.01). The older group had the lower incidence rates of depression symptoms,
      compared with the younger group (P < 0.01). The workers divorced or with the
      bereft spouse had the higher incidence rate of depression symptoms than the
      workers married and unmarried (P < 0.05). The workers with middle school
      education had the higher incidence rates of depression symptoms than those with
      master degree. Incidence rates in the most occupational groups were more than
      30%. The significant difference was shown between the different jobs (P < 0.01).
      The difference of the adjusted means among three groups of different depression
      score were analyzed. The results showed the workers with definite depression
      symptoms had the higher scores than the other two groups in physical factors,
      role ambiguity, role conflict, job monotony, mental load, responsibility for
      persons, job future ambiguity, job hazards, type A behavior and work locus of
      control, and social support (P < 0.05, P < 0.01). The former had the lower scores
      than the other two groups in the scores of promotion, participation, autonomy,
      task identity, feedback, friendship opportunity, speed control, training
      adequacy, challenge, self-esteem, organizational commitment, and coping
      strategies. Fifteen variables entered the predictive equation of depression score
      explaining 33.1% of variance. CONCLUSION: There are serious mental health
      problems in the occupational population in our country. Stressors and
      personalities affect the mental health.

PMID- 16600130
TI  - [Relationship between genetic polymorphism in hMTH1c.83, hOGG1c.326 and hMYHc.335
      and risks of chronic benzene poisoning].
AB  - OBJECTIVE: To explore the relationship between genetic polymorphisms in hMTH1,
      hOGG1 and hMYH and risks of chronic benzene poisoning (CBP). METHODS: A case
      control study was conducted. One hundred and fifty-two BP patients and 152
      workers occupationally exposed to benzene without poisoning manifestations were
      investigated. The polymerase chain reaction restrained fragment length
      polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide
      polymorphisms (SNPs) on c.83 of hMTH1 gene, c.326 of hOGG1 gene and c.335 of hMYH
      gene. RESULTS: There were 2.51 times (OR(adj) = 2.51, 95% CI: 1.14-5.49, P =
      0.02) and 2.49 times (OR(adj) = 2.49, 95% CI: 1.52-4.07, P < 0.01) risks of BP
      for individuals carrying genotypes of hMTH1c.83Val/Met + Met/Met or
      hOGG1c.326Cys/Cys compared with individuals carrying genotypes of
      hMTH1c.83Val/Val or hOGG1c.326Ser/Cys + Ser/Ser, respectively. Compared with
      individuals carrying genotypes of hOGG1c.326Cys/Cy and hMYHc.335 is/His at the
      same time, there was 0.33 times (OR(adj) = 0.33, 95% CI = 0.15-0.72, P = 0.01)
      risks of BP for these with genotypes of hOGG1c.326Ser/Cys + Ser/Ser and
      hMYHc.335His/Gln + Gln/Gln simultaneously. In the smoking group, there was 0.15
      times (OR(adj) = 0.15, 95% CI: 0.03-0.68, P = 0.01) risks of BP for subjects
      carrying genotypes of hMYHc.335His/Gln + Gln/Gln compared with these carrying
      genotypes of hMYHc.335His/His. CONCLUSION: Polymorphisms of hMTH1 Val83 Met and
      hOGG1 Ser326Cys may contribute to altered risks of CBP, and potential interaction
      may exist among polymorphisms of hOGG1 Ser326Cys and hMYH His335Gln.

PMID- 16600131
TI  - [Expression of renal nuclear factor-kappaB, transforming growth factor-beta and
      fibronectin of rats exposed to lead].
AB  - OBJECTIVE: To investigate the role of lead in the expression of the renal
      fibrosis related nuclear factor kappaB (NF-kappaB), transforming growth factor
      (TGF-beta) and fibronectin (FN) in rat kidney and the possible molecule mechanism
      of lead induced renal fibrosis. METHODS: Thirty-two Sprague-Dawley rats were
      randomized into 4 groups. Group A was fed with distilled water as control group.
      Group B, C and D were fed with the water including 0.5% lead acetate continuously
      for 1, 2 or 3 months respectively. At the end of treatment, the expressions of
      renal NF-kappaB, TGF-beta and FN were detected by immunohistochemistry and RT
      PCR. RESULTS: The immunohistochemistry analysis showed that expressions of NF
      kappaB in group B, C and D (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/-
      0.0839 respectively) were continuously increased as compared with that in group A
      (0.1464 +/- 0.0624). The RT-PCR analysis showed that expressions of NF-kappaB in
      group B, C and D (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538
      respectively) were also increased as compared with that in group A (0.3608 +/-
      0.0550). However, there was no change for TGF-beta in 4 groups except that it was
      increased markedly in group D (0.5225 +/- 0.0416) as compared with that in group
      A (0.4645 +/- 0.0461) by RT-PCR. The expressions of FN in group C and D (0.4243
      +/- 0.0595 and 0.4917 +/- 0.0891 by immunohistochemistry; 0.8650 +/- 0.0880 and
      0.8714 +/- 0.0980 by RT-PCR) were increased as compared with those in group A
      (0.3530 +/- 0.0490 by immunohistochemistry and 0.7432 +/- 0.0639 by RT-PCR).
      CONCLUSION: The lead can increase the expression of renal NF-kappaB, TGF-beta and
      FN in rats, which may be related to the lead induced renal fibrosis in rats.

PMID- 16600132
TI  - [Protective effect of tert-butylhydroquinone on bone marrow cells in rats from
      cytotoxicity induced by benzene in vitro].
AB  - OBJECTIVE: To investigate the protective effect of tert-butylhydroquinone on bone
      marrow cells in rats from cytotoxicity induced by benzene in vitro. METHODS: The
      bone marrow cells in rats were divided into two groups randomizedly. Cells of the
      control group were stimulated by 0, 5, 10, 15, 20 mmol/L benzene for 2, 4, 6
      hours respectively. Cells of the tBHQ-pretreated group were treated by 100
      micromol/L tBHQ for 12 hours followed by the same conditions as the control
      group. The DNA damage was detected by single cell gel electrophoresis assay
      (SCGE) and cell apoptosis was examined by flow cytometry. The activities of NAD
      (P) H: quinone oxidoreductase (NQO1) in bone marrow cells of rats were also
      measured before benzene treatment in two groups. RESULTS: In control group, the
      DNA damage and the apoptosis of bone marrow cells was increased with the growing
      concentration and time of benzene treatment. The DNA migration and the lengths of
      DNA migration of the bone marrow cells in the rats under 5, 10, 15, 20 mmol/L
      benzene treatment in the tBHQ-pretreated group were significantly lower than
      those in control group at the same time point (P < 0.05). The apoptosis of the
      bone marrow cells in the rats stimulated by 15, 20 mmol/L benzene for 2 hours and
      10, 15, 20 mmol/L benzene for 4 hours as well as 5, 10, 15, 20 mmol/L benzene for
      6 hours were also significantly lower than those in control group (P < 0.05). The
      activities of NQO1 in the bone marrow cells in the rats were increased after tBHQ
      treatment (P < 0.01) (1.62 +/- 0.16 min(-1).mg(-1) vs. the control group: 0.95 +/
      0.08 min(-1).mg(-1)). CONCLUSION: The benzene can induce the DNA damage and the
      apoptosis of bone marrow cells in rats in a time dependent and dose dependent
      manner to some extent. The tBHQ can protect the bone marrow cells in rats from
      the cytotoxicity induced by benzene, which can be partly explained by the
      increase of the NQO1 activity induced by tBHQ.

PMID- 16600133
TI  - [Protection of lithium on hippocampal cholecystokinin and nitric oxide synthase
      neuron in lead exposed rats].
AB  - OBJECTIVE: To investigate the effect of lithium on hippocampal cholecystokinin
      (CCK) and neuronal nitric oxide synthase (nNOS) positive neurons and its
      relationship to the learning and memory ability of lead exposed rats. METHODS:
      Wistar rats were randomly divided into the control group, the lead group, four
      lead + LiCl (3, 30, 300, 3,000 mg/kg) groups. Four lead + LiCl groups were fed
      with food containing 3, 30, 300, 3,000 mg/kg LiCl respectively. The lead + LiCl
      groups and the lead group were administered with distilled water containing 0.2%
      PbAc. The body weight was measured and the difference of body development was
      observed. Y-maze test was used for studying the effects of lead on the learning
      and the memory ability in rats. ABC immunohistochemistry was used for
      investigating the changes of CCK positive neurons in hippocampus of lead-exposed
      rats. RESULTS: Compared with the control group and the lead + LiCl groups, the
      learning and memory ability of lead exposed rats was significantly higher (P <
      0.05). The number of CCK positive neurons in hippocampus lead exposed rats fed
      with lithium (3, 30, 300 mg/kg) was significantly higher than that in the lead
      exposed rats (P < 0.05). CONCLUSION: The lead may damage the learning-memory
      ability of the rats. It might be related to the changes of CCK positive neurons
      in hippocampus in lead exposed rats. The lithium of the low dose might play an
      important role in preventing lead-induced damages.

PMID- 16600134
TI  - [Microenvironment of positive pressure powered air purifying medical protective
      equipment].
AB  - OBJECTIVE: To study the filtration efficiency of a positive pressure powered air
      purifying medical protective equipment and the effect of the flow rate on the
      microenvironment of the equipment. METHODS: The filtration efficiency of high
      efficiency particulate air (HEPA) filter was measured with the biologic aerosol
      of simulating virus (Escherichia coli bacteriophage f(2)). The simulation work
      was done at the walk rate of 4 km/h in summer. The effect of the flow rate on the
      oxygen content, the carbon dioxide content, the temperature and the humidity of
      the microenvironment of the equipment was investigated. The clinical experiments
      were conducted in three appointed hospital for fighting against SARS. RESULTS:
      The HEPA filter could filtrate 99.99% simulating viruses in the air. When the
      flow rate ranged from 75 to 125 L/min, the microenvironment parameters of the
      equipment were: the oxygen content was between 19.6% and 20.1% (the physiological
      safety limit is more than 14.6%); the carbon dioxide content ranged from 0.43% to
      0.57% (the physiological safety limit is less than 1.0%); the temperature was
      between 32.0 degrees C to 32.2 degrees C; the humidity ranged from 49.7% to 59.4%
      (the physiological safety limit is the temperature 31 degrees C and the humidity
      85% or temperature 38 degrees C and humidity 50%). Each microenvironment
      parameter met the demand of a healthy person under the normal workload. In the
      clinical experiments, the doctors wearing the equipment who performed the
      tracheotomy for a SARS patient in a deep coma were not infected. CONCLUSION: The
      medical protective equipment can protect the doctor and nurse in SARS
      contaminated areas effectively and improve their work conditions.

PMID- 16600135
TI  - [Protective effect of mouse 2.5s nerve growth factor on PC12 cells from injury
      induced by 2, 5-hexanedione].
AB  - OBJECTIVE: To explore whether the nerve growth factor has protective effects on
      PC12 cells from injury induced by 2, 5-hexanedione. METHODS: With PC12 cells as
      the model of neurons, different concentrations of NGF were added into the culture
      of PC12 cells. Then cell viability was tested with MTT. The DNA fragment was
      observed with agarose gel electrophoresis. The apoptosis ratio was tested with
      flow cytometry (FACS). The p53 protein was detected with western blot. The
      differences among the groups were compared. RESULTS: Cell viabilities were
      increased with the increase of the concentrations of NGF (P < 0.05). The DNA
      fragment, the apoptosis ratio and the expression of p53 were all decreased with
      the increase of the concentrations of NGF (P < 0.05). CONCLUSION: The NGF might
      have direct nutritional effects on PC12 cells, and protect them from injury
      induced by 2, 5 HD. Moreover, it might also have anti-apoptosis effect to some
      extent.

PMID- 16600136
TI  - [Mechanism of reactive oxygen species in manganese chloride-induced apoptosis in
      PC12 cells].
AB  - OBJECTIVE: To explore the mechanism of reactive oxygen species (ROS) in manganese
      chloride (MnCl(2))-induced apoptosis in PC12 cells. METHODS: The model that
      MnCl(2) induced apoptosis in PC12 cells was established. The apoptotic effect of
      MnCl(2) on PC12 cells was analyzed with the MTT, the flow cytometry and the DNA
      fragmentation. The production of ROS and ATP in MnCl(2)-induced apoptosis of PC12
      cells was examined. The influence of MnCl(2) on the expression of bcl-xl, bax and
      the activity of Caspase 3 was also analyzed. RESULTS: MnCl(2) triggered PC12
      cells apoptosis in a dose-and time-dependent manner (P < 0.01). The rate of
      apoptosis was significantly increased (P < 0.01) when MnCl(2) of 2 mmol/L induced
      PC12 cells for 36 hours. The production of ROS was increased (P < 0.001) and the
      quantity of ATP was decreased (P < 0.01) in PC12 cells with the same inducement
      of MnCl(2). The expression of bcl-xl was inhibited and the bax was activated in
      this process (P < 0.01). Caspase 3 was also activated (P < 0.01). CONCLUSION:
      MnCl(2) induces apoptosis of PC12 cells, which is related to the increase of ROS,
      the inhibition of the mitochondria and the activation of Caspase 3.

PMID- 16600137
TI  - [Effect of aluminum trichloride on dissociated Ca2+ in Hippocampus neuron cell as
      well as learning and memory].
AB  - OBJECTIVE: To investigate the effect of aluminum chloride on dissociated Ca(2+)
      in hippocampus neuron cells in mice and the relationship to the learning and
      memory. METHODS: Male ICR mice in the three intoxicated groups were administered
      with the double distilled water containing AlCl(3) (10, 50, 300 mg.kg(-1).d(-1))
      while those in the control group were administered with the double distilled
      water for 100 days. The methods of behavior toxicology such as Morris swim maze
      were used for studying the effect of aluminum chloride on the changes of learning
      and memory in mice. With calcium sensitive fluorescence indicator Fura-2 as the
      fluorescent probe, the influence of the subchronic exposure to Al on the
      dissociated Ca(2+) in hippocampus neuron cells was observed. RESULTS: The
      dissociated Ca(2+) in hippocampus neuron cells in the middle dosage group and the
      high dosage group [(412.25 +/- 53.20), (467.37 +/- 32.85) times] was lower than
      those in the control group [(293.91 +/- 32.21) times] respectively (P < 0.01),
      and correlated positively with the dose and dissociated Ca(2+) (r = 0.861, P <
      0.01). Compared with the control group, the latent period was lengthened (P <
      0.05) in the middle dosage and the high dosage group. CONCLUSION: The subchronic
      exposure to AlCl(3) in mice affects the dissociated Ca(2+) in hippocampus neuron
      cells. The increase of dissociated Ca(2+) in hippocampus neuron cells may be
      correlated with the disfunction of cognition in the aluminium intoxicated mice.

PMID- 16600139
TI  - [Influence of professional boron exposure on quality of male sperms].

PMID- 16600138
TI  - [Arterial blood gas analysis in Lipopolysaccharide-heat co-stressed rats].
AB  - OBJECTIVE: To observe the change in vital signs and arterial blood gas in
      Lipopolysaccharide (LPS)-injected heat exposed rats. METHODS: Male pathogen-free
      Wistar rats were randomly assigned to the following groups: saline-injected
      normothermic control (C-Group), saline-injected heat exposed (H-Group), LPS
      injected normothermic control (L-Group), LPS-injected heat exposed (HL-Group).
      Rectal temperature (Tr), heart rate (HR), mean arterial pressure (MAP), arterial
      blood gas were continually monitored. RESULTS: (1) The rats in HL-Group displayed
      significantly high values of Tr (43.04 degrees C +/- 0.11 degrees C) and HR [(660
      +/- 42) beats/min] and low values of MAP [(49.0 +/- 3.5) mm Hg] compared with C
      Group. There was a significant difference in the values of Tr, HR, and MAP
      between HL-Group and L-Group and in the values of HR and MAP between HL-Group and
      H-Group. (2) The values of PaO(2), HCO(3)(-), PaCO(2) were significantly lower
      than those in C-Group at 40 min after LPS-injected heat stress. At 120 min, the
      PaO(2) [(11.59 +/- 1.11) kPa], HCO(3)(-) [(10.42 +/- 1.06) mmol/L], PaCO(2)
      [(2.82 +/- 0.81) kPa] in HL-Group were significantly lower than those in L-Group.
      A significant difference in the values of HCO(3)(-) and PaCO(2) between HL-Group
      and H-Group was also observed. CONCLUSION: LPS-injected heat stress primes the
      rat to advance and augment the change in vital signs, arterial blood gas, and
      systemic inflammatory response syndrome.

PMID- 16600140
TI  - [The harmful compositions in fifty-two types of adhesives and analysis for the
      contents].

PMID- 16600141
TI  - [Pathological study on uterotrophic assay].

PMID- 16600142
TI  - [Synergetic effect of flue gases and arsenic on DNA injury in lymphocytes].

PMID- 16600143
TI  - [Injury in myocardial cells induced by citreoviridin].

PMID- 16600144
TI  - [Toxicity of aluminum chloride for primarily cultured neural cells of the
      cerebral cortex in rats].

PMID- 16600145
TI  - [Effect of aluminum on concentration of calcium in cells of the cerebral cortex].

PMID- 16600146
TI  - [Investigation on accidents of nitrite poisoning in factories].

PMID- 16600147
TI  - [Methods of determination of several types of aldehyde compounds in air].

PMID- 16600148
TI  - [Common problems in diagnosis and identification of professional diseases and the
      solutions].

PMID- 16600149
TI  - [Influence of acrylonitrile on morphology of testicle tissue in mice].

PMID- 16600150
TI  - [Brief introduction of primary professional health service].

PMID- 16600151
TI  - [Toxic encephalopathy induced by acute carbon bisulfide: a one-case report].

PMID- 16600152
TI  - [Subacute arsenic poisoning: a three case report].

PMID- 16600155
TI  - Genetic determinants of the metabolic syndrome.
AB  - Complex interactions between inherited factors and the environment determine an
      individual's susceptibility to type 2 diabetes mellitus and related syndromes.
      Insulin resistance, obesity, hypertension, and hyperlipidemia frequently precede
      the development of frank diabetes and aggregate in families. Several genome-wide
      scans have recently been performed in families with this constellation of
      findings, called the "metabolic syndrome." These analyses strongly support an
      inherited component to the syndrome. In this review, we provide an overview of
      the evidence in support of an inherited contribution to the metabolic syndrome
      and the search for causative genomic regions. When multiple genome scans
      involving different patient cohorts implicate a common genomic region as
      susceptible to the metabolic syndrome, it is highly likely that causative genes
      reside in that area. Identification of these genes will dramatically improve our
      understanding of the mechanisms that underlie the metabolic syndrome, and could
      lead to novel treatment strategies. It is hoped that these therapies will also
      prevent the future development of type 2 diabetes mellitus and atherosclerotic
      complications, both common among individuals affected by the metabolic syndrome.

PMID- 16600154
TI  - Proximal tubular function and salt sensitivity.
AB  - Blood pressure response to changes in dietary salt intake is highly variable
      among individuals. This heterogeneity results from the combined effects of
      genetic and environmental determinants. In recent years, considerable progress
      has been made in our understanding of the pathogenic mechanisms leading to the
      development of salt-sensitive hypertension. Much information has come from the
      investigation of rare monogenic forms of salt-sensitive hypertension, which has
      focused attention on alterations of renal sodium handling occurring essentially
      in the distal nephron. In this paper, we review the experimental, clinical,
      genetic, and epidemiologic evidence suggesting that proximal tubular function is
      also an important determinant of the blood pressure response to salt, which
      deserves greater attention.

PMID- 16600156
TI  - Update on G-protein polymorphisms in hypertension.
AB  - The classic candidate gene approach continues to be the most prevalent tool in
      the search for the genetic basis of essential hypertension. With the list of
      candidate genes for this disorder steadily increasing, the pertussis toxin
      sensitive inhibitory G protein (Gi) protein beta3 subunit (GNB3) gene has
      remained "sizzling," challenging the domination of the renin-angiotensin system.
      Is the genetic variability of GNB3 a causative factor underlying the pathogenesis
      of essential hypertension? Is the "functional" polymorphism, C825T, only
      "another" of the countless single nucleotide polymorphisms (SNP) for this
      disorder after all? As such, does its presence merely reinforce our confidence
      that essential hypertension is indeed polygenic? Should the C825T polymorphism be
      used in clinical practice and individualized antihypertensive treatment?
      Currently, there are still more questions than answers. In this review, in
      conjunction with our own research, we bring readers up to date on the latest
      developments of GNB3 polymorphisms in the field of hypertension.

PMID- 16600157
TI  - Fat tissue metabolism and adrenal steroid secretion.
AB  - Obesity has reached epidemic proportions in Western societies, contributing to
      metabolic diseases, hypertension, and vascular diseases. White adipose tissue has
      traditionally been regarded merely as lipid, and consequently, as energy storage.
      However, recent data revealed the importance of adipose tissue as a highly active
      endocrine organ and its involvement in the body's metabolism and homeostasis.
      Obesity is associated with several endocrine disorders, including adrenocortical
      malfunction. Because of the central role of adrenal function in the body's
      homeostasis, adrenal malfunction is important in the development of other obesity
      related abnormalities. Therefore, in this short review, we summarize recent data
      on obesity-induced changes in adrenocortical mineralocorticoid, glucocorticoid,
      and androgen secretions and their consequences for metabolism.

PMID- 16600158
TI  - The future of endothelin-receptor antagonism as treatment for systemic
      hypertension.
AB  - Endothelin (ET) is an endogenous peptide secreted predominantly by endothelial
      cells that mediates its effects via vasoconstriction and hypertrophy of vascular
      smooth muscle. Because the role of ET has been described in multiple pathologic
      processes in cardiovascular disease, including hypertension, there has been a
      strong interest in the development of therapeutic agents that inhibit ET
      receptors. ET receptor antagonists have shown much promise in disease states such
      as pulmonary arterial hypertension, essential hypertension, and various forms of
      secondary hypertension. This review serves to summarize the current role of ET
      and ET receptor antagonists in both the pathophysiology and the treatment of
      hypertension.

PMID- 16600159
TI  - The renin-angiotensin system and atherosclerosis.
AB  - Atherosclerosis is an insidious and complex disease of large- and medium-sized
      arteries. The primum movens of the disease is characterized by co-localization of
      lipids, inflammatory cells, and fibrous elements within the intima of vessels.
      Starting as a "fatty streak," the disease evolves over decades into complex
      lesions that can progress toward a stable or a vulnerable plaque. During the past
      decade, we have become familiar with the features of the vulnerable plaque;
      however, the mechanisms that cause a stable plaque to change into a vulnerable
      lesion with its dramatic clinical outcome still remain largely unknown. There is
      good evidence from epidemiologic, experimental, and clinical studies that the
      renin-angiotensin system, via its active peptide angiotensin II, may contribute
      to atherosclerosis development and progression, not only by increasing blood
      pressure but also through multiple direct effects. Moreover, recent studies have
      shown a potential role for angiotensin II as a mediator of plaque vulnerability.

PMID- 16600160
TI  - Endothelial arginase: a new target in atherosclerosis.
AB  - Decreased endothelial nitric oxide (NO) bioavailability as it relates to
      endothelial dysfunction plays an important role in various cardiovascular
      disorders, including athero-sclerosis. Recent research has provided evidence that
      endothelial dysfunction in atherosclerosis is not primarily caused by decreased
      endothelial NO synthase (eNOS) gene expression, but rather deregulation of eNOS
      enzymatic activity, which contributes to the increased oxidative stress in
      atherosclerosis. Among other mechanisms, the substrate L-arginine is an important
      limiting factor for NO production. Emerging evidence demonstrates that L-arginine
      is not only converted to NO via eNOS, but also metabolized to urea and l
      ornithine via arginase in endothelial cells. Hence, arginase competes with eNOS
      for the substrate L-arginine, resulting in deceased NO production. There are an
      increasing number of studies showing that enhanced arginase gene expression
      and/or activity contribute to endothelial dysfunction in various cardiovascular
      disorders, including atherosclerosis. Thus, endothelial arginase may represent a
      new therapeutic target in atherosclerosis.

PMID- 16600161
TI  - Nitrates as adjunct hypertensive treatment.
AB  - Isolated systolic hypertension (ISH) is an important cause of strokes and heart
      failure among the elderly, but it is difficult to control in some elderly
      patients, even with combination antihypertensive therapy. The presence of a
      prominent reflection wave in the arterial pulse-wave profile of such patients
      signifies that adjuvant nitrate therapy may prove effective in lowering pulse
      pressure. This reflection arises in the muscular arteries and is caused by
      arterial stiffness associated with hypertension and other cardiovascular risk
      factors, probably including endothelial dysfunction. By acting directly on the
      arterial wall, nitrates produce endothelium-independent vasorelaxation. The
      reflection wave and the contribution this makes to pulse pressure are thereby
      ablated. Controlled trials of the use of isosorbide mononitrate and isosorbide
      dinitrate in ISH have shown that these agents decrease systolic blood pressure as
      well as pulse pressure, and with the mononitrate, efficacy appears to be
      unimpaired by nitrate tolerance.

PMID- 16600162
TI  - Regulation of antioxidant and oxidant enzymes in vascular cells and implications
      for vascular disease.
AB  - Data from numerous studies demonstrate that oxidative stress plays an important
      role in the pathogenesis of vascular disease. Oxidative stress leads to many
      pathologic events, such as inactivation of nitric oxide, lipid oxidation,
      enhanced mitogenicity and apoptosis of vascular cells, and increased expression
      and activation of redox-sensitive genes, which contribute to atherogenesis at all
      stages of the disease. Multiple enzymes are expressed in vascular cells that are
      involved in the elimination and production of reactive oxygen species, including
      the superoxide dismutases, catalase, thioredoxin reductase, glutathione
      peroxidase, NAD(P)H oxidase, xanthine oxidase, myeloperoxidase, and endothelial
      nitric oxide synthase. Several agonists and pathologic conditions that predispose
      to vascular disease induce changes in the expression and activity levels of these
      antioxidant and oxidant enzyme systems, leading to modulation of vascular oxygen
      radical load. Identification of key enzymes and mechanisms of vascular oxidative
      stress is important for the development of novel, specific pharmacologic
      interventions.

PMID- 16600163
TI  - The link between Glut-1 and hypertension in diabetic nephropathy.
AB  - Nephropathy is a major diabetic microvascular complication; both metabolic and
      hemodynamic perturbations play critical roles in its occurrence and progression
      toward end-stage renal disease. Improvements in metabolic and blood pressure
      control have been shown to confer protection from this diabetic complication. In
      this article, we review the facilitative glucose transporter Glut-1, its
      regulation, and its potential role in linking metabolic and hemodynamic
      perturbations in the pathophysiologic processes that lead to kidney injury in
      diabetes. We propose that an auto-maintaining mechanism of hemodynamic
      perturbations and increased tissue angiotensin II may be involved in the
      initiation and maintenance of a loop in which transforming growth factor beta1
      and Glut-1 upregulation play important roles in the pathophysiology of diabetic
      induced kidney lesions. The understanding of the molecular mechanisms that link
      glomerular hypertension and excessive glucose metabolism may provide insight into
      new therapeutic strategies for the treatment of diabetic renal disease.

PMID- 16600164
TI  - Endothelium, aging, and hypertension.
AB  - Endothelium plays a primary role in modulating vascular tone and structure
      through production of the relaxing factor nitric oxide (NO), which also protects
      the vessel wall against the pathogenesis of atherosclerosis and thrombosis. A
      dysfunctioning endothelium due to reduced NO availability and increased
      production of oxidative stress is considered an early indicator of
      atherothrombotic damage and of cardiovascular events. Aging is associated with
      the development of cardiovascular structural and functional alterations, which
      can explain the age-related increase in cardiovascular risk. Advancing age is
      associated with endothelial dysfunction in both normotensive subjects and
      essential hypertensive patients, an alteration caused by a progressive impairment
      of the NO pathway and production of oxidative stress. Once oxidative stress
      production becomes detectable, NO availability is totally compromised. Essential
      hypertension represents a mere acceleration of the changes induced by aging on
      endothelial function. Currently, dynamic physical activity represents the only
      effective intervention in preventing age-related impaired endothelium-dependent
      vasodilation in aged healthy individuals.

PMID- 16600165
TI  - Small artery remodeling in hypertension and diabetes.
AB  - The development of structural changes in the systemic vasculature is the end
      result of established hypertension. In essential hypertension, small artery
      smooth muscle cells are restructured around a smaller lumen, and there is no net
      growth of the vascular wall, whereas in some secondary forms of hypertension and
      in non-insulin-dependent diabetes mellitus, a hypertrophic remodeling may be
      detected. Indices of small resistance artery structure, such as the tunica media
      to internal lumen ratio, may have a strong prognostic significance in
      hypertensive patients. Various antihypertensive drugs seem to have different
      effects on vascular structure. A complete normalization of small resistance
      artery structure was demonstrated in hypertensive patients, after prolonged and
      effective therapy with angiotensin-converting enzyme inhibitors, angiotensin II
      receptor blockers, and calcium antagonists. Few data are available in diabetic
      hypertensive patients; however, blockade of the renin-angiotensin system seems to
      be effective in this regard.

PMID- 16600166
TI  - Young driver accidents in the UK: the influence of age, experience, and time of
      day.
AB  - Young drivers, especially males, have relatively more accidents than other
      drivers. Young driver accidents also have somewhat different characteristics to
      those of other drivers; they include single vehicle accidents involving loss of
      control; excess speed for conditions; accidents during darkness; accidents on
      single carriageway rural roads; and accidents while making cross-flow turns (i.e.
      turning right in the UK, equivalent to a left turn in the US and continental
      Europe). A sample of over 3000 accident cases was considered from midland British
      police forces, involving drivers aged 17-25 years, and covering a two year
      period. Four types of accident were analysed: right-turns; rear-end shunts; loss
      of control on curves; and accidents in darkness. Loss of control on curves and
      accidents in darkness were found to be a particular problem for younger drivers.
      It was found that cross-flow turn accidents showed the quickest improvement with
      increasing driver experience, whereas accidents occurring in darkness with no
      street lighting showed the slowest rate of improvement. 'Time of day' analyses
      suggested that the problems of accidents in darkness are not a matter of
      visibility, but a consequence of the way young drivers use the roads at night.
      There appears to be a large number of accidents associated with voluntary risk
      taking behaviours of young drivers in 'recreational' driving.

PMID- 16600167
TI  - Early mid-trimester serum relaxin, soluble CD163, and cervical length in women at
      high risk for preterm delivery.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between
      serum concentrations of relaxin and soluble CD163 with cervical length and
      preterm delivery in women with previous spontaneous preterm delivery. STUDY
      DESIGN: Sixty-one of 69 pregnant women with a previous spontaneous preterm had
      serum relaxin and soluble CD163 measured at week 16 (range, 12-25 weeks). End
      points were cervical length and gestational age at delivery. RESULTS: Of the 61
      women, 26% had >1 previous spontaneous preterm delivery; 84% were black; 87% were
      unmarried; 13% were smokers, and 39% were delivered before 37 weeks of gestation.
      Neither relaxin (median, 368 ng/L; range, 83-1493 ng/L) nor soluble CD163 (2.4
      mg/L; range, 0.86-6.85 mg/L) correlated with cervical length or gestational age
      at delivery. Black women had higher relaxin levels (436 vs 205 ng/L; P = .002),
      but soluble CD163 levels were similar among racial groups. CONCLUSION: Relaxin
      and soluble CD163 measured at 16 weeks of gestation are not clinically useful
      predictors of short cervical length or preterm delivery in women with a previous
      spontaneous preterm delivery.

PMID- 16600168
TI  - Optimal Sox-based fluorescent chemosensor design for serine/threonine protein
      kinases.
AB  - Fluorescent chemosensors of protein kinase activity provide a continuous, high
      throughput sensing format for the study of the roles of these enzymes, which are
      crucial for regulating cellular function. Specifically, chemosensors using the
      nonnatural amino acid, Sox, and physiological Mg(2+) levels report
      phosphorylation with dramatic fluorescence changes that are amenable to real-time
      and high-throughput analysis. In this article, we report 15 probes for a total of
      six distinct serine/threonine kinases with large fluorescence increases and good
      reactivity toward the target kinase. The sensing mechanism is detailed, and the
      optimal sensing motif is determined. These versatile and powerful sensors provide
      tools for researchers studying the roles of the targeted kinases in signal
      transduction, and the design principles provide guidelines for the generation of
      future fluorescent chemosensors for any serine/threonine kinase.

PMID- 16600169
TI  - Probing gender-specific metabolism differences in humans by nuclear magnetic
      resonance-based metabonomics.
AB  - The measurement of metabolite profiles that are interpreted to yield biomarkers
      using multivariate data analysis is now a well-established approach for gaining
      an improved understanding of the impact of genetic modifications, toxicological
      and therapeutic interventions, and exposure to stimuli (e.g., noxious agents,
      stressors, nutrients) on the network of transcripts, proteins, and metabolites
      present in cells, tissues, or whole organisms. This has been termed metabonomics.
      In this study, multivariate analysis of (1)H nuclear magnetic resonance (NMR)
      spectra of metabolite profiles of urine and plasma from 150 healthy humans
      revealed that in young people and/or individuals with low body mass indexes,
      females had higher rates of lipid biosynthesis than did males, whereas males had
      higher rates of protein turnover than did females. With increasing age, overall
      lipid biosynthesis decreased in females, whereas metabolism increasingly favored
      lipid synthesis over protein turnover in males. By relating the derived
      metabonomic data to known metabolic pathways and published biochemical data, it
      appears that females synthesize relatively more lipoproteins and unsaturated
      lipids than do males. Furthermore, the changes in lipid biosynthesis and urinary
      citrate excretion in females showed a positive correlation. Estrogen most likely
      plays an essential role in the regulation of, and communication between, protein
      and lipid biosynthesis by controlling pH in mitochondria and the cytoplasm and
      hence the observed altered citrate levels.

PMID- 16600170
TI  - Studies on genomic DNA topology and stability in brain regions of Parkinson's
      disease.
AB  - DNA damage has been postulated as a mechanism of neuronal death in Parkinson's
      disease (PD). In the present study, genomic DNA was isolated from eight brain
      regions (frontal, temporal, and occipital cortex, hippocampus, caudate/putamen,
      thalamus, cerebellum, and midbrain) from five neuropathologically confirmed cases
      of Parkinson's disease and six control brains and analyzed for the presence of
      single and double strand breaks, melting temperature, EtBr intercalation, DNAse
      digestion pattern, and DNA conformations. The results showed that DNA from
      midbrain in PD accumulated significantly higher number of strand breaks than age
      matched controls. Caudate nucleus/putamen, thalamus, and hippocampus also showed
      more DNA fragmentation compared to control brains. Circular dichroism studies
      showed that DNA conformation was altered with imprecise base stacking in
      midbrain, caudate nucleus/putamen, thalamus, and hippocampus in PD. However, DNA
      from frontal, temporal, and occipital cortex, and cerebellum was not affected
      significantly in PD group as compared to controls. This study provides a
      comprehensive database on stability, damage, and conformations of DNA in
      different regions in brains of PD patients.

PMID- 16600171
TI  - Protein free diet feeding: effects on sympathetic activity and salivary evoked
      secretion in the submandibular gland of the rat.
AB  - Protein restriction impairs the salivary flow rate and composition in human and
      rats. The aim of the present work was to establish the effect of low protein
      (casein 5%) and protein free (casein 0%) isocaloric diets on sympathetic activity
      and salivary evoked secretion in the submandibular gland (SMG) of the rat. After
      21 days, rats fed casein 0% presented: (a) a significant shift to the left of the
      dose-response curves (DRC) to the autonomic agonists-norepinephrine (NE),
      methoxamine, isoproterenol (ISO) and methacholine; (b) increased food consumption
      (p<0.001); (c) decreased body (p<0.001) and SMG (p<0.001) weights maintaining
      SMG/body (w/w) relation; (d) enhanced submandibular alpha1-adrenoceptor number
      without changes in the apparent dissociation constant (Kd); (e) increased
      submandibular NE content (p<0.05) and phosphoinositoside hydrolysis (p<0.001);
      (f) decreased submandibular tyrosine hydroxylase activity (TH) (p<0.01). Casein
      5% feeding increased food consumption (p<0.01) and reduced body weight (p<0.05).
      This protein restriction increased metacholine-evoked salivation, but it altered
      neither submandibular sympathetic activity nor sympathetic-induced salivary
      secretion as compared to the Control group (C) fed a similar diet containing
      25.5% protein. Present results suggest that in the adult rat, a protein free diet
      during 21 days lowers SMG sympathetic and cholinergic activity leading to
      supersensitivity as revealed by up-regulation of alpha1-adrenergic receptor
      number and increased autonomic-evoked salivation.

PMID- 16600173
TI  - Proton pumping in the bc1 complex: a new gating mechanism that prevents short
      circuits.
AB  - The Q-cycle mechanism of the bc1 complex explains how the electron transfer from
      ubihydroquinone (quinol, QH2) to cytochrome (cyt) c (or c2 in bacteria) is
      coupled to the pumping of protons across the membrane. The efficiency of proton
      pumping depends on the effectiveness of the bifurcated reaction at the Q(o)-site
      of the complex. This directs the two electrons from QH2 down two different
      pathways, one to the high potential chain for delivery to an electron acceptor,
      and the other across the membrane through a chain containing heme bL and bH to
      the Qi-site, to provide the vectorial charge transfer contributing to the proton
      gradient. In this review, we discuss problems associated with the turnover of the
      bc1 complex that center around rates calculated for the normal forward and
      reverse reactions, and for bypass (or short-circuit) reactions. Based on rate
      constants given by distances between redox centers in known structures, these
      appeared to preclude conventional electron transfer mechanisms involving an
      intermediate semiquinone (SQ) in the Q(o)-site reaction. However, previous
      research has strongly suggested that SQ is the reductant for O2 in generation of
      superoxide at the Q(o)-site, introducing an apparent paradox. A simple gating
      mechanism, in which an intermediate SQ mobile in the volume of the Q(o)-site is a
      necessary component, can readily account for the observed data through a
      coulombic interaction that prevents SQ anion from close approach to heme bL when
      the latter is reduced. This allows rapid and reversible QH2 oxidation, but
      prevents rapid bypass reactions. The mechanism is quite natural, and is well
      supported by experiments in which the role of a key residue, Glu-295, which
      facilitates proton transfer from the site through a rotational displacement, has
      been tested by mutation.

PMID- 16600175
TI  - Amyloid precursor protein is involved in staurosporine induced glial
      differentiation of neural progenitor cells.
AB  - Staurosporine (STS) has been reported as not only a pro-apoptotic agent, but also
      a terminal differentiation inducer in several neuroblastoma cell lines. Here, we
      report involvement of amyloid precursor protein (APP) in a STS induced astrocytic
      differentiation of human neural progenitor cells (NT-2/D1). We found that STS
      treated NT-2/D1 cells expressed astrocyte-specific glial fibrillary acidic
      protein (GFAP), aspartate transporter, and glutamate transporter-1 with a
      distinctive astrocytic morphology. STS treatment increased GFAP promoter activity
      and increased expression and secretion of APP in NT-2/D1 cell culture.
      Overexpressed APP enhanced GFAP promoter activity and expression of GFAP, while
      gene silencing of APP by RNA interference decreased GFAP expression. These
      results indicate involvement of APP in STS induced astrocytic differentiation of
      NT-2/D1 cells. Furthermore, suppression of ERK1/2 phosphorylation, which is known
      to regulate APP expression by a MEK1 inhibitor, PD098059, reduced both APP and
      GFAP expression in STS treated NT-2/D1 cells. Thus, STS may induce astrocytic
      differentiation of NT-2/D1 by increasing APP levels associate with activation of
      ERK pathway.

PMID- 16600174
TI  - Hydrodynamic properties of porcine bestrophin-1 in Triton X-100.
AB  - Bestrophin-1 (Best-1) is an integral membrane protein, defects in which cause
      Best vitelliform macular dystrophy. Best-1 is proposed to function as a Cl-
      channel and/or a regulator of Ca++ channels. A tetrameric (or pentameric)
      stoichiometry has been reported for recombinant best-1. Using a combination of
      gel exclusion chromatography and velocity sedimentation we examined the
      quaternary structure of native best-1 and found that it migrates as a single
      species with a Stokes radius of 7.3 nm, sedimentation coefficient (S20,w) of 4.9,
      and partial specific volume (nu) of 0.80 ml/g. The mass of the protein-detergent
      complex is calculated to be 206 kDa, with the protein component estimated to be
      approximately 138 kDa. Given a monomeric mass of 68 kDa, we conclude that native
      best-1 solubilized with Triton X-100 is a homodimer. The differences between this
      observation and a prior report were examined by comparing recombinant best-1 with
      tissue derived best-1 using gel exclusion chromatography. Much of the recombinant
      best-1 eluted in the column void (Vo) fraction, unlike that extracted from RPE
      cells. We conclude that the minimal functional unit of best-1 is dimeric. This
      stoichiometry differs from that previously measured for recombinant best-1,
      suggesting that further studies are necessary to determine the stoichiometry of
      functional best-1 in RPE membranes.

PMID- 16600176
TI  - G-CSF prevents the progression of atherosclerosis and neointimal formation in
      rabbits.
AB  - Granulocyte colony-stimulating factor (G-CSF) prevents left ventricular
      remodeling after myocardial infarction, but its effect on atherosclerosis is
      unknown. We examined two kinds of rabbit atherosclerosis models. Myocardial
      infarction-prone Watanabe heritable hyperlipidemic (WHHL-MI) rabbits were treated
      with G-CSF or saline for 7 days from 14 months old. The vascular injury models
      were created by inflating angioplasty balloon in the iliac artery of rabbits and
      were divided into G-CSF and saline group. G-CSF significantly reduced the
      stenosis score of coronary artery and lipid plaque area of thoracic aorta in WHHL
      MI rabbits at 4 weeks after the treatment. In the vascular injury model, G-CSF
      significantly prevented an increase in neointima/media ratio at 4 weeks after the
      treatment. G-CSF accelerated the reendothelialization of denuded arteries, and
      the pretreatment with nitric oxide synthase inhibitor significantly inhibited it.
      These results suggest that G-CSF has a therapeutic potential for the progression
      of atherosclerosis.

PMID- 16600177
TI  - CRIT peptide interacts with factor B and interferes with alternative pathway
      activation.
AB  - Complement C2 receptor inhibitor trispanning (CRIT) inhibits the classical
      pathway (CP) C3 convertase formation by competing with C4b for the binding of C2.
      The C-terminal 11-amino-acid of the first CRIT-extracellular domain (CRIT-H17)
      has a strong homology with a sequence in the C4beta chain, which is responsible
      for the binding of C2. Since the CP and alternative pathway (AP) C3 convertases
      have many functional and structural similarities, we further investigated the
      effects of CRIT-H17 on the AP. The factor D-mediated cleavage of factor B (FB)
      was blocked by CRIT-H17. By ELISA and immunoblot, CRIT-H17 was shown to bind FB.
      CRIT-H17 had no decay activity on the C3bBb complex as compared to decay
      accelerating factor. Binding of CRIT-H17 to FB did not interfere with the
      assembly of C3bB complex. In a haemolytic assay using C2-deficient serum, CRIT
      H17 interfered with AP complement activation.

PMID- 16600178
TI  - Immune-mediated beta-cell destruction in vitro and in vivo-A pivotal role for
      galectin-3.
AB  - Pro-apoptotic cytokines are toxic to the pancreatic beta-cells and have been
      associated with the pathogenesis of Type 1 diabetes (T1D). Proteome analysis of
      IL-1beta exposed isolated rat islets identified galectin-3 (gal-3) as the most up
      regulated protein. Here analysis of human and rat islets and insulinoma cells
      confirmed IL-1beta regulated gal-3 expression of several gal-3 isoforms and a
      complex in vivo expression profile during diabetes development in rats. Over
      expression of gal-3 protected beta-cells against IL-1beta toxicity, with a
      complete blockage of JNK phosphorylation, essential for IL-1-mediated apoptosis.
      Mutation scanning of regulatory and coding regions of the gal-3 gene (LGALS3)
      identified six polymorphisms. A haplotype comprising three cSNPs showed
      significantly increased transmission to unaffected offspring in 257 T1D families
      and replicated in an independent set of 170 T1D families. In summary, combined
      proteome-transcriptome-genome and functional analyses identify gal-3 as a
      candidate gene/protein in T1D susceptibility that may prove valuable in future
      intervention/prevention strategies.

PMID- 16600179
TI  - A novel interaction [corrected] of nucleolin with Rad51.
AB  - Nucleolin associates with various DNA repair, recombination, and replication
      proteins, and possesses DNA helicase, strand annealing, and strand pairing
      activities. Examination of nuclear protein extracts from human somatic cells
      revealed that nucleolin and Rad51 co-immunoprecipitate. Furthermore, purified
      recombinant Rad51 associates with in vitro transcribed and translated nucleolin.
      Electroporation-mediated introduction of anti-nucleolin antibody resulted in a 10
      to 20-fold reduction in intra-plasmid homologous recombination activity in human
      fibrosarcoma cells. Additionally, introduction of anti-nucleolin antibody
      sensitized cells to death induced by the topoisomerase II inhibitor, amsacrine.
      Introduction of anti-Rad51 antibody also reduced intra-plasmid homologous
      recombination activity and induced hypersensitivity to amsacrine-induced cell
      death. Co-introduction of anti-nucleolin and anti-Rad51 antibodies did not
      produce additive effects on homologous recombination or on cellular sensitivity
      to amsacrine. The association of the two proteins raises the intriguing
      possibility that nucleolin binding to Rad51 may function to regulate homologous
      recombinational repair of chromosomal DNA.

PMID- 16600180
TI  - Novel chitosan/collagen scaffold containing transforming growth factor-beta1 DNA
      for periodontal tissue engineering.
AB  - The current rapid progression in tissue engineering and local gene delivery
      system has enhanced our applications to periodontal tissue engineering. In this
      study, porous chitosan/collagen scaffolds were prepared through a freeze-drying
      process, and loaded with plasmid and adenoviral vector encoding human
      transforming growth factor-beta1 (TGF-beta1). These scaffolds were evaluated in
      vitro by analysis of microscopic structure, porosity, and cytocompatibility.
      Human periodontal ligament cells (HPLCs) were seeded in this scaffold, and gene
      transfection could be traced by green fluorescent protein (GFP). The expression
      of type I and type III collagen was detected with RT-PCR, and then these
      scaffolds were implanted subcutaneously into athymic mice. Results indicated that
      the pore diameter of the gene-combined scaffolds was lower than that of pure
      chitosan/collagen scaffold. The scaffold containing Ad-TGF-beta1 exhibited the
      highest proliferation rate, and the expression of type I and type III collagen up
      regulated in Ad-TGF-beta1 scaffold. After implanted in vivo, EGFP-transfected
      HPLCs not only proliferated but also recruited surrounding tissue to grow in the
      scaffold. This study demonstrated the potential of chitosan/collagen scaffold
      combined Ad-TGF-beta1 as a good substrate candidate in periodontal tissue
      engineering.

PMID- 16600181
TI  - G protein-coupled receptor for diapause hormone, an inducer of Bombyx embryonic
      diapause.
AB  - Bombyx diapause hormone was the first chemical substance identified as a maternal
      control factor that arrests offspring development. However, the molecular
      mechanisms by which the hormone transduces the signal to the oocyte that induces
      embryonic diapause immediately after mesoderm segmentation are not fully
      understood. Here, we describe a cDNA for a G protein-coupled diapause hormone
      receptor with seven transmembrane domains. Its amino-acid sequence shows a high
      level of similarity to the receptors of mammalian neuromedin U and insect
      regulatory peptide, an FXPRL-amide C-terminus. When expressed in a Xenopus oocyte
      system, the receptor exhibited the highest affinity (EC(50), approximately 70nM)
      for diapause hormone, when compared with other Bombyx FXPR/KL-amide peptides.
      Diapause hormone without amidation at the C-terminus, which never induces
      embryonic diapause in vivo, had no effect in this heterologous expression system.
      The mRNA is expressed in the ovaries during Bombyx pupal-adult development. These
      results strongly indicate that the cDNA encodes the diapause hormone receptor.

PMID- 16600182
TI  - A Small Ras-like protein Ray/Rab1c modulates the p53-regulating activity of PRPK.
AB  - PRPK phosphorylates serine-15 residue of p53 and enhances transcriptional
      activity. PRPK possesses a bipartite nuclear localization signal and localizes in
      nucleus when over-expressed in cells. However, intrinsic PRPK localizes mainly in
      the cytosol in situ. While studying the mechanisms in the distribution of
      intrinsic PRPK, we identified a PRPK binding protein, an ubiquitously expressed
      Small Ras-like GTPase, Rab1c, also named Ray or Rab35. The over-expressed Ray was
      distributed in the nucleus, cytosol, and cell membrane. Both Ray wild type and
      GTP-restrictively binding mutant Ray-Q67L, but not guanine nucleotide unstable
      binding mutant Ray-N120I, partially distributed the over-expressed PRPK to the
      cytosol and also suppressed the PRPK-induced p53-transcriptional activity
      profoundly. A Small Ras-like GTPase protein Ray was thus indicated to modulate
      p53 transcriptional activity of PRPK.

PMID- 16600183
TI  - Cold-inducible RNA binding protein is required for the expression of adhesion
      molecules and embryonic cell movement in Xenopus laevis.
AB  - We have previously shown that the Xenopus homologue of cold-inducible RNA binding
      protein, XCIRP-1, is required for the morphogenetic migration of the pronephros
      during embryonic development. However, the underlying molecular mechanisms remain
      elusive. Here, we report that XCIRP is essential for embryonic cell movement, as
      suppression of XCIRP by microinjection of anti-sense mRNA and morpholino
      antisense oligonucleotides (MOs) significantly reduced protein expression,
      inhibited the cell migration rate, and inhibited eFGF and activin-induced animal
      cap elongation. By immunoprecipitation and RT-PCR, we further showed that the
      mRNA of a panel of adhesion molecules, including alphaE- and beta-catenin, C- and
      E-cadherin, and paraxial proto-cadherin, are the targets of XCIRP. Consistently,
      in animal cap explant studies, suppression of XCIRP by MOs inhibited the
      expression of these adhesion molecules, while over-expression of sense XCIRP-1
      mRNA fully rescued this inhibition. Taken together, these results suggest for the
      first time that XCIRP is required to maintain the expression of adhesion
      molecules and cell movement during embryonic development.

PMID- 16600185
TI  - High-density lipoprotein is a potential growth factor for adrenocortical cells.
AB  - The entry of cholesterol contained within high-density lipoprotein (HDL) into
      adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII
      Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA
      1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective
      uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to
      those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited
      the proliferation of an adrenocortical cell line and the incorporation of
      [(3)H]thymidine into the cells. This effect was sensitive to wortmannin, an
      inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies
      revealed that the inhibitory action of mCLA required the transcriptional factor
      AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin.
      These findings raise the possibility that the inhibitors of the effects of HDL
      may be of therapeutic value for adrenocortical tumor.

PMID- 16600184
TI  - Mutational analysis of the Lem3p-Dnf1p putative phospholipid-translocating P-type
      ATPase reveals novel regulatory roles for Lem3p and a carboxyl-terminal region of
      Dnf1p independent of the phospholipid-translocating activity of Dnf1p in yeast.
AB  - Lem3p-Dnf1p is a putative aminophospholipid translocase (APLT) complex that is
      localized to the plasma membrane; Lem3p is required for Dnf1p localization to the
      plasma membrane. We have identified lem3 mutations, which did not affect
      formation or localization of the Lem3p-Dnf1p complex, but caused a synthetic
      growth defect with the null mutation of CDC50, a structurally and functionally
      redundant homologue of LEM3. Interestingly, these lem3 mutants exhibited nearly
      normal levels of NBD-labeled phospholipid internalization across the plasma
      membrane, suggesting that Lem3p may have other functions in addition to
      regulation of the putative APLT activity of Dnf1p at the plasma membrane.
      Similarly, deletion of the COOH-terminal cytoplasmic region of Dnf1p affected
      neither the localization nor the APLT activity of Dnf1p at the plasma membrane,
      but caused a growth defect in the cdc50Delta background. Our results suggest that
      the Lem3p-Dnf1p complex may play a role distinct from its plasma membrane APLT
      activity when it substitutes for the Cdc50p-Drs2p complex, its redundant partner
      in the endosomal/trans-Golgi network compartments.

PMID- 16600186
TI  - Recql4 haploinsufficiency in mice leads to defects in osteoblast progenitors:
      Implications for low bone mass phenotype.
AB  - The cellular and molecular mechanisms that underlie skeletal abnormalities in
      defective Recql4-related syndromes are poorly understood. Our objective in this
      study was to explore the function of Recql4 in osteoblast biology both in vitro
      and in vivo. Immunohistochemistry on adult mouse bone showed Recql4 protein
      localization in active osteoblasts around growth plate, but not in fully
      differentiated osteocytes. Consistent with this finding, Recql4 gene expression
      was high in proliferating mouse osteoblastic MC3T3.E1 cells and decreased as
      cells progressively lost their proliferation activity during differentiation.
      Recql4 overexpression in osteoblastic cells exhibited higher proliferation
      activity, while its depletion impeded cell growth. In addition, bone marrow
      stromal cells from male Recql4+/- mice had fewer progenitor cells, including
      osteoprogenitors, indicated by reduced total fibroblast colony forming units (CFU
      f) and alkaline phosphatase-positive CFU-f colonies concomitant with reduced bone
      mass. These findings provide evidence that Recql4 functions as a regulatory
      protein during osteoprogenitor proliferation, a critical cellular event during
      skeleton development.

PMID- 16600187
TI  - Assembly of the otoconia complex to the macular sensory epithelium of the
      vestibule.
AB  - In the inner ear, specificity of stimulus perception is achieved by associating
      the sensory epithelia of the three mechanoreceptor organs, the utricle/saccule,
      cristae, and cochlea, with distinct types of acellular matrices. Only the utricle
      and saccule have an extremely dense matrix, the otoconial complex, which overlies
      the sensory epithelium (macula) and provides inertial mass to generate shearing
      forces essential for the mechanoreceptors to sense gravity and linear
      acceleration. Such sensation is necessary for spatial orientation and balance.
      The importance of otoconia is clearly demonstrated by the impact of balance
      disorders upon the elderly population that involve otoconia degeneration, as well
      as by canalithiasis and cupulolithiasis, in which otoconia are dislocated. This
      underscores the need to understand how otoconia are formed and maintained and how
      to prevent their degeneration. To date, a number of otoconia-related proteins
      have been identified mostly in mice and bony fish. Although most of these
      proteins are also present in other structures of the inner ear, a distinct
      collection of proteins in the macula plus the unique ionic microenvironment of
      the endolymph near its epithelium likely contribute to the site-specific
      calcification of otoconia. Based on the current literature and ongoing research,
      this mini-review postulates a working model of how the otoconia complex is
      assembled specifically above the macular sensory epithelium of the vestibule. The
      central hypothesis of this model is that proteins are critical in sequestering
      calcium for crystallization in the calcium-poor endolymph. The review also sets
      forth some issues that need to be resolved in the future.

PMID- 16600188
TI  - The paintfill method as a tool for analyzing the three-dimensional structure of
      the inner ear.
AB  - The mammalian inner ear is a complex epithelial tube designed to detect sound,
      angular and linear acceleration, as well as gravity. The major parts of the ear
      include three orthogonal semicircular canals, a central vestibule, a coiled
      cochlea, and an endolymphatic duct and sac allowing fluid balance with the
      cerebrospinal system. Located throughout this tubular system are six separate
      sensory areas composed of hair cells and support cells that are essential for the
      transduction of hearing and balance information. Deafness and vestibular
      dysfunction are extremely common sensory disorders in the human population, with
      one in every 1000 children born profoundly hearing impaired and many progressive
      forms diagnosed later in life. Approximately 20-30% of patients with congenital
      sensorineural hearing loss demonstrate radiographic abnormalities of the inner
      ear, indicating that malformations of the inner ear make a significant
      contribution to the high frequency of deafness and balance disorders.
      Unfortunately, the very complexity that makes the inner ear such an exquisite
      structure has also made it an extremely difficult organ to tackle for
      researchers. Here, I describe a histological method involving paintfilling of the
      inner ear that provides easy analysis of the three-dimensional structure of this
      complex organ. The paintfill method can be used to quickly assess inner ear
      morphology and can help identify defects that may cause or contribute to deafness
      and/or vestibular dysfunction.

PMID- 16600189
TI  - General anesthesia as a factor affecting impulse activity and neuronal responses
      to putative neurotransmitters.
AB  - Although it is evident that general anesthesia should affect impulse activity and
      neurochemical responses of central neurons, there are limited studies in which
      these parameters were compared in both awake and anesthetized animal
      preparations. We used single-unit recording coupled with iontophoresis to examine
      impulse activity and responses of substantia nigra pars reticulata (SNr) neurons
      to GABA, glutamate (GLU), and dopamine (DA) in rats in awake, unrestrained
      conditions and during chloral hydrate anesthesia. SNr neurons in both conditions
      had similar organization of impulse flow, but during anesthesia, they have lower
      mean rates and discharge variability than in awake conditions. In individual
      units, discharge rate in awake, quietly resting rats was almost three-fold more
      variable than during anesthesia. These cells in both conditions were highly
      sensitive to iontophoretic GABA, but the response was stronger during anesthesia.
      In contrast to virtually no responses to GLU in awake conditions, most SNr
      neurons during anesthesia were excited by GLU; the response occurred
      preferentially in slow-firing units, which were atypical of awake conditions.
      Consistent with no postsynaptic DA receptors on SNr neurons, iontophoretic DA was
      ineffective in altering discharge rates in awake conditions, but often induced
      weak excitations during anesthesia. Although SNr neurons are autoactive,
      generating discharges without any excitatory input (i.e., in vitro), their
      impulse activity and responses to natural neurochemical inputs are strongly
      affected by general anesthesia. Some alterations appear to be specific to the
      general anesthetic used, while others probably reflect changes in the activity of
      afferent inputs, brain metabolism and neurotransmitter uptake that are typical to
      any type of general anesthesia. Therefore, an awake, freely moving animal
      preparation appears to be advantageous for studying impulse activity and
      neurochemical interactions at single-neuron level during physiologically relevant
      conditions.

PMID- 16600190
TI  - Effects of central leptin infusion on the reward-potentiating effect of D
      amphetamine.
AB  - It was previously reported that chronic food restriction and maintenance of rats
      at 75-80% of initial body weight enhanced the reward-potentiating effect of D
      amphetamine in the lateral hypothalamic self-stimulation (LHSS) paradigm.
      Moreover, the enhancement reversed in parallel with body weight recovery when ad
      libitum access to food was reinstated. The present study tested the hypothesis
      that hypoleptinemia during food restriction is necessary for expression of
      enhanced drug reward. In Experiment 1, intracerebroventricular (i.c.v.) infusion
      of leptin (0.5 microg/0.5 microl/hr for 8 days) in food-restricted rats did not
      alter the rewarding effect of D-amphetamine (0.5 mg/kg, i.p.). Considering that
      i.c.v. leptin may not diffuse into deep brain regions where direct effects on
      drug reward sensitivity may be exerted, effects of acute bilateral microinjection
      of leptin (0.5 microg) in ventral tegmental area and nucleus accumbens were
      tested in Experiment 2 and found to have no effect. In Experiment 3, chronic
      i.c.v. leptin infusion in ad libitum fed rats decreased food intake and body
      weight and enhanced the rewarding effect of D-amphetamine. Sensitivity to D
      amphetamine returned to normal as body weight recovered following cessation of
      leptin infusion. This result suggests that weight loss, whether from hormone
      induced appetite suppression or experimenter-imposed food restriction, is
      sufficient to enhance drug reward sensitivity. Experiment 4 tested whether food
      restriction in the absence of body weight loss alters drug reward sensitivity.
      Rats received chronic i.c.v. infusion of the orexigenic melanocortin receptor
      antagonist, SHU9119 (0.02 microg/0.5 microl/hr for 12 days), and a subset were
      pair-fed to vehicle-infused controls. Although these subjects ingested
      approximately 50% of the amount of food ingested by free-feeding SHU9119-infused
      rats, they displayed no weight loss and no change in sensitivity to D
      amphetamine. Together, results of this study support the importance of weight
      loss, but not leptin, in the enhancement of drug reward sensitivity.

PMID- 16600191
TI  - Dendritic spine plasticity: looking beyond development.
AB  - Most excitatory synapses in the CNS form on dendritic spines, tiny protrusions
      from the dendrites of excitatory neurons. As such, spines are likely loci of
      synaptic plasticity. Spines are dynamic structures, but the functional
      consequences of dynamic changes in these structures in the mature brain are
      unclear. Changes in spine density, morphology, and motility have been shown to
      occur with paradigms that induce synaptic plasticity, as well as altered sensory
      experience and neuronal activity. These changes potentially lead to an alteration
      in synaptic connectivity and strength between neuronal partners, affecting the
      efficacy of synaptic communication. Here, we review the formation and
      modification of excitatory synapses on dendritic spines as it relates to
      plasticity in the central nervous system after the initial phase of
      synaptogenesis. We will also discuss some of the molecular links that have been
      implicated in both synaptic plasticity and the regulation of spine morphology.

PMID- 16600192
TI  - Calpeptin provides functional neuroprotection to rat retinal ganglion cells
      following Ca2+ influx.
AB  - Apoptosis of retinal ganglion cells (RGCs) impairs vision in glaucoma patients.
      RGCs are also degenerated in multiple sclerosis (MS), resulting in loss of visual
      perception in MS patients. We examined the involvement of calpain and caspase
      cascades in apoptosis of the rat retinal ganglion cell line RGC-5 following 24 h
      of exposure to 250 nM ionomycin (IMN) or 300 units/ml interferon-gamma (IFN
      gamma) and then evaluated functional neuroprotection with 2 microM calpeptin (CP,
      a calpain-specific inhibitor). Morphological and biochemical features of
      apoptosis were detected in RGC-5 cells following exposure to IMN or IFN-gamma.
      Fura-2 assay determined significant increases in intracellular free [Ca2+]
      following exposure to IMN or IFN-gamma. Pretreatment with CP for 1 h prevented
      Ca2+ influx, proteolytic activities, and apoptosis in RGC-5 cells. Western blot
      analyses showed an increase in activities of calpain and caspase-12, upregulation
      of Bax:Bcl-2 ratio, release of cytochrome c from mitochondria, and increase in
      caspase-9 and caspase-3 activities during apoptosis. Increased caspase-3 activity
      was also confirmed by a colorimetric assay. Activation of caspase-8 and cleavage
      of Bid to tBid in RGC-5 cells following exposure to IFN-gamma indicated co
      operation between extrinsic and intrinsic pathways of apoptosis. Patch-clamp
      recordings showed that pretreatment with CP attenuated apoptosis and maintained
      normal whole-cell membrane potential, indicating functional neuroprotection.
      Taken together, our results demonstrated that Ca2+ overload could be responsible
      for activation of calpain and caspase cascades leading to apoptotic death of RGC
      5 cells and CP provided functional neuroprotection.

PMID- 16600194
TI  - The sarcoplasmic reticulum as the primary target of reperfusion protection.

PMID- 16600193
TI  - Inner ear proteomics of mouse models for deafness, a discovery strategy.
AB  - Inner ear dysfunction is often associated with defective hair cells. Therefore,
      hair cells are the focus of study in many of the mouse mutants showing auditory
      and vestibular deficits. However, harvesting sufficient numbers of hair cells
      from the tiny bony mouse inner ear for proteomic analysis is challenging. New
      approaches that would take advantage of mouse mutants and avoid processing steps,
      such as decalcification or microdissetion, would be more suitable for proteomic
      analysis. Here, we propose a novel approach called SSUMM-Subtractive Strategy
      Using Mouse Mutants. SSUMM takes advantage of the differences between control and
      affected or mutant samples. We predict that SSUMM would be a useful method in
      proteomics, especially in those cases in which the investigator must work with
      small numbers of diverse cell types from a tiny organ. Here, we discuss the
      potential utility of SSUMM to unravel the protein expression profiles of hair
      cells using the Pou4f3 mouse mutant as an example. Pou4f3 mutant mice exhibit a
      total loss of inner and outer hair cells, but supporting cells remain relatively
      intact in the cochlea, thus providing an excellent model for identifying proteins
      and transcripts that are specific to the hair cell at all life stages. SSUMM
      would maximize the sensitivity of the analyses while obviating the need for
      tedious sessions of microdissection and collection of hair cells. By comparing
      the mutant to control ears at specific time points, it is possible to identify
      direct targets of a gene product of interest. Further, SSUMM could be used to
      identify and analyze inner ear development markers and other known genes/proteins
      that are coexpressed in the ear. In this short technical report, we also discuss
      protein-profiling approaches suitable for SSUMM and briefly discuss other
      approaches used in the field of proteomics.

PMID- 16600195
TI  - IL-21 dependent IgE production in human and mouse in vitro culture systems is
      cell density and cell division dependent and is augmented by IL-10.
AB  - IL-21 is known to enhance immunoglobulin production using human in vitro models.
      Using either PBMC or purified tonsilar B cells both stimulated with anti-CD40, IL
      4+/-IL-21, this enhancement was shown to correlate with increased cell division
      especially for IgE and to a lesser extent for IgM and total IgG. Cell division
      was monitored by CFSE staining and maximum cell division was found at low initial
      cell plating densities. A correlation between increased cell division and IL-10
      mediated enhancement of IgE production was also seen; however, increased cell
      division plays a smaller role with IL-10 than IL-21. This is further emphasized
      in that when IL-10 and IL-21 were added together there was a further synergistic
      increase in IgE seen, but no accompanying further increase in cell division. The
      mouse system was also examined for IL-21 effects as a function of cell
      concentration, and as in humans, IL-21 added to murine cells increased IgE
      production over IL-4/CD40 stimulated cells at lower cell concentrations; however,
      IL-21 significantly reduced IgE at higher plated cell concentrations.

PMID- 16600196
TI  - CD28 is required for induction and maintenance of immunological memory in toxin
      reactive CD4+ T cells in vivo.
AB  - We previously reported that Vbeta3+ CD4+ T cells maintained a protracted
      expansion, with the phenotypes of memory Th2 cells, for 30 days in C57BL/6 (B6)
      mice implanted with SEA-containing mini-osmotic pumps. In the present study, we
      followed the fate of Vbeta3+ CD4+ T cells in CD28-/- mice. Vbeta3+ CD4+ T cells
      increased to a degree similar to that of B6 Vbeta3+ CD4+ T cells until day 10
      after implantation, then declined rapidly reaching the control level by 28 days.
      Remaining Vbeta3+ CD4+ T cells at that time did not exhibit memory phenotypes nor
      Th2-deviated responses. The rapid drop in Vbeta3+ CD4+ T cells in CD28-/- mice
      was attributable to upregulated induction of apoptosis owing to marginal
      inductions of Bcl-2 and Bcl-xL. Collectively, these data indicate CD28 to play
      critical roles in the generation and maintenance of SEA-reactive CD4+ T cells in
      vivo.

PMID- 16600198
TI  - Proteins involved in lipid translocation in eukaryotic cells.
AB  - Since the first discovery of ATP-dependent translocation of lipids in the human
      erythrocyte membrane in 1984, there has been much evidence of the existence of
      various ATPases translocating lipids in eukaryotic cell membranes. They include P
      type ATPases involved in inwards lipid transport from the exoplasmic leaflet to
      the cytosolic leaflet and ABC proteins involved in outwards transport. There are
      also ATP-independent proteins that catalyze the passage of lipids in both
      directions. Five P-type ATPase involved in lipid transport have been genetically
      characterized in yeast cells, suggesting a pool of several proteins with
      partially redundant activities responsible for the regulation of lipid asymmetry.
      However, expression and purification of individual yeast proteins is still
      insufficient to allow reconstitution experiments in liposomes. In this review, we
      want to give an overview over current investigation efforts about the
      identification and purification of proteins that may be involved in lipid
      translocation.

PMID- 16600197
TI  - Mitochondrial glutathione transport: physiological, pathological and
      toxicological implications.
AB  - Although most cellular glutathione (GSH) is in the cytoplasm, a distinctly
      regulated pool is present in mitochondria. Inasmuch as GSH synthesis is primarily
      restricted to the cytoplasm, the mitochondrial pool must derive from transport of
      cytoplasmic GSH across the mitochondrial inner membrane. Early studies in liver
      mitochondria primarily focused on the relationship between GSH status and
      membrane permeability and energetics. Because GSH is an anion at physiological
      pH, this suggested that some of the organic anion carriers present in the inner
      membrane could function in GSH transport. Indeed, studies by Lash and colleagues
      in isolated mitochondria from rat kidney showed that most of the transport (>80%)
      in that tissue could be accounted for by function of the dicarboxylate carrier
      (DIC, Slc25a10) and the oxoglutarate carrier (OGC, Slc25a11), which mediate
      electroneutral exchange of dicarboxylates for inorganic phosphate and 2
      oxoglutarate for other dicarboxylates, respectively. The identity and function of
      specific carrier proteins in other tissues is less certain, although the OGC is
      expressed in heart, liver, and brain and the DIC is expressed in liver and
      kidney. An additional carrier that transports 2-oxoglutarate, the
      oxodicarboxylate or oxoadipate carrier (ODC; Slc25a21), has been described in rat
      and human liver and its expression has a wide tissue distribution, although its
      potential function in GSH transport has not been investigated. Overexpression of
      the cDNA for the DIC and OGC in a renal proximal tubule-derived cell line, NRK
      52E cells, showed that enhanced carrier expression and activity protects against
      oxidative stress and chemically induced apoptosis. This has implications for
      development of novel therapeutic approaches for treatment of human diseases and
      pathological states. Several conditions, such as alcoholic liver disease,
      cirrhosis or other chronic biliary obstructive diseases, and diabetic
      nephropathy, are associated with depletion or oxidation of the mitochondrial GSH
      pool in liver or kidney.

PMID- 16600199
TI  - Molecular dynamics simulations of gramicidin A in a lipid bilayer: from structure
      function relations to force fields.
AB  - Molecular dynamics simulations of membrane proteins have become a popular tool
      for studying their dynamic features, which are not easily accessible by
      experiments. Whether the force fields developed for globular proteins are
      adequate this purpose is an important question that is often glossed over. Here
      we determine the permeation properties of potassium ions in the gramicidin A
      channel in a lipid bilayer from free energy simulations, and compare the results
      to experimental data. In particular, we check the dependence of the free energy
      barriers ions face at the channel center on the membrane size. The results
      indicate that there is a serious problem with the current rigid force fields
      independent of the membrane size, and new, possibly polarizable, force fields
      need to be developed to resolve this problem.

PMID- 16600200
TI  - Protein-lipid interactions and surface activity in the pulmonary surfactant
      system.
AB  - Pulmonary surfactant is a lipid-protein complex, synthesized and secreted by the
      respiratory epithelium of lungs to the alveolar spaces, whose main function is to
      reduce the surface tension at the air-liquid interface to minimize the work of
      breathing. The activity of surfactant at the alveoli involves three main
      processes: (i) transfer of surface active molecules from the aqueous hypophase
      into the interface, (ii) surface tension reduction to values close to 0 mN/m
      during compression at expiration and (iii) re-extension of the surface active
      film upon expansion at inspiration. Phospholipids are the main surface active
      components of pulmonary surfactant, but the dynamic behaviour of phospholipids
      along the breathing cycle requires the necessary participation of some specific
      surfactant associated proteins. The present review summarizes the current
      knowledge on the structure, disposition and lipid-protein interactions of the
      hydrophobic surfactant proteins SP-B and SP-C, the two main actors participating
      in the surface properties of pulmonary surfactant. Some of the methodologies
      currently used to evaluate the surface activity of the proteins in lipid-protein
      surfactant preparations are also revised. Working models for the potential
      molecular mechanism of SP-B and SP-C are finally discussed. SP-B might act in
      surfactant as a sort of amphipathic tag, directing the lipid-protein complexes to
      insert and re-insert very efficiently into the air-liquid interface along
      successive breathing cycles. SP-C could be essential to maintain association of
      lipid-protein complexes with the interface at the highest compressed states, at
      the end of exhalation. The understanding of the mechanisms of action of these
      proteins is critical to approach the design and development of new clinical
      surfactant preparations for therapeutical applications.

PMID- 16600201
TI  - Telomerase activity in fine needle aspiration biopsy samples: application to
      diagnosis of human thyroid carcinoma.
AB  - BACKGROUND: The diagnosis of thyroid follicular carcinoma by fine needle
      aspiration biopsy is a well known problem in thyroid pathology. METHODS: We
      evaluated telomerase activity (TA) in 85 fine needle aspiration biopsy (FNAB)
      samples from patients with thyroid nodules. Surgery samples from patients with
      tumor or follicular adenomas were also analyzed. RESULTS: Twenty of the FNAB
      samples corresponded to carcinomas and were positive to telomerase assay (TA >10
      Units). Among them, 4 follicular carcinomas and 1 papillary carcinoma were
      labeled as indeterminate by FNAB cytological examination. Four percent false
      positive cases and no false negative cases for TA in FNABs were reported. FNAB
      samples from follicular adenomas were diagnosed as indeterminate by cytological
      examination, but they showed no detectable TA. Tumor tissues from patients with
      follicular or papillary thyroid carcinomas presented TA >10 Units, whereas
      follicular adenoma tissues (benign nodules) showed no TA. CONCLUSION: Our results
      showed a good correlation between TA in FNAB samples and tumor/nodule thyroid
      tissue. This suggested that use of TA as a biological marker of malignancy might
      be a useful tool in the diagnosis of follicular thyroid carcinomas or follicular
      thyroid adenomas using FNAB samples.

PMID- 16600202
TI  - Evaluation of different bone markers in hemodialyzed patients.
AB  - BACKGROUND: Routinely, nephrologists rely on different biochemical markers like
      intact PTH (iPTH), bone-specific alkaline phosphatase (BALP), plasmatic calcium
      and phosphate. The aim of the present study was to evaluate different other bone
      markers like N-terminal propeptide of type 1 procollagen (P1NP), active isoform
      5b of the tartrate-resistant acid phosphatase (TRAP 5b) and beta-crossLaps (CTXS)
      as well as full-length PTH (wPTH), presumed non-(1-84) PTH, and their ratio in
      the diagnosis of renal osteodystrophy with high and low turnover. We also
      determined 25 hydroxyvitamin D (25VTD), 1-25 dihydroxyvitamin D and homocystein
      (HCY). METHODS: We performed those parameters on 73 patients with end-stage renal
      disease according to the manufacturers' instructions. RESULTS: There were very
      strong correlations between the bone markers concentrations, particularly between
      BALP and P1NP (r=0.953). We did not observe any correlation between the ratio
      whole PTH/non-(1-84) PTH and any of the usual bone markers. This ratio was
      significantly (p<0.05) higher in low and high bone turnover patients than in
      normal patients according to the K/DOQI. We found a correlation between low
      levels of 25VTD and high levels of HCY. CONCLUSIONS: BALP offers the best
      clinical and analytical profile as the easier marker of choice in hemodialyzed
      patients for the diagnosis of bone disease.

PMID- 16600203
TI  - B-type natriuretic peptide and amino terminal proBNP predict one-year mortality
      in short of breath patients independently of the baseline diagnosis of acute
      destabilized heart failure.
AB  - BACKGROUND: The aim of the present study was to demonstrate the capability of B
      type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) as
      prognostic markers in patients with dyspnoea as a chief complaint. METHODS: BNP
      and NT-proBNP plasma concentrations were obtained from 251 short of breath
      patients presenting to the emergency department of a tertiary care hospital.
      Patients with acute coronary syndromes or trauma were excluded. The endpoint was
      defined as all-cause mortality, and the study participants were followed up for
      365 days from the time they attended the emergency department. RESULTS: Of the
      251 patients, 62 died and 189 stayed alive during follow-up. In the present
      study, optimal cut off levels for the prediction of survival were 454 ng/L for
      BNP, and 2060 ng/L for NT-proBNP. Mortality was higher in patients with baseline
      BNP and NT-proBNP concentrations above these cut off levels (log rank p<0.001;
      hazard ratios, 0.325 and 0.357, respectively). In multivariate Cox proportional
      hazards regression analyses, elevated BNP/NT-proBNP, low systolic blood pressure,
      and renal dysfunction were predictors of mortality even when the baseline
      diagnosis of acute destabilized heart failure was factored into the model.
      CONCLUSIONS: Both BNP and NT-proBNP measures obtained from short of breath
      patients presenting to an emergency department may be predictive of one-year all
      cause mortality independently of the baseline diagnosis of acute destabilized
      heart failure.

PMID- 16600204
TI  - N-Acetyltransferase-1 gene polymorphisms and correlation between genotype and its
      activity in a central Chinese Han population.
AB  - BACKGROUND: We investigated the arylamine N-acetyltransferase-1 (NAT1) gene
      polymorphisms and the correlation between genotype and phenotype in a Chinese Han
      population. METHODS: Peripheral blood from 140Han people were collected and
      analyzed for NAT1 genotypes by allele-specific PCR combining with PCR-based
      restriction fragment length polymorphism-based procedure. The NAT1 phenotype were
      determined according to the NAT1 enzyme kinetics in leukocytes by HPLC method and
      the values of intrinsic clearance (Cl(int)) and V(max) and Michaelis constant
      (K(m)) of NAT1 were calculated. RESULTS: The NAT1 genotype of Chinese Han
      populations was distinguished accurately and the NAT1 activity were detected in
      32 objects with different genotypes. The allelic frequencies of NAT1*3, NAT1*4,
      NAT1*10 and NAT1*11 from 140 Han people, were 0.082, 0.496, 0.40 and 0.022,
      respectively. Compared with the activity of wild genotype NAT1 *4/*4, the
      activity of the homozygote or heterozygote NAT1*10 genotype which includes the
      NAT1 *4/*10, the NAT1 *10/*10 and the NAT1 *3/*10 was significantly high
      (p<0.05). The activity of the NAT1 *11/*11 and NAT1 *4/*11 was lower than that of
      the homozygote or heterozygote NAT1*10 genotype (p<0.05), but no difference with
      the activity of wild genotype and the NAT1 *4/*3 and NAT1 *3/*3. CONCLUSION: The
      distribution of the NAT1 genotype in a Chinese Han population was different from
      that in other countries. The activity of NAT1 showed significant variance from
      leukocytes with different genotypes.

PMID- 16600205
TI  - Lipid and protein oxidation and antioxidant status in patients with
      angiographically proven coronary artery disease.
AB  - OBJECTIVES: We aimed to evaluate the association of lipid peroxidation, protein
      oxidation and antioxidant system, and to assess an association with the severity
      of the disease, in patients with and without coronary artery disease (CAD)
      documented by coronary angiography. DESIGN AND METHODS: The population included
      208 patients, undergoing clinically indicated coronary angiography. While the
      subjects with normal coronary angiograms (n=54) were evaluated as controls, the
      patients with CAD (n=154) were divided into three categories according to the
      number of diseased coronaries; one-vessel (n=50), two-vessels (n=51) and three
      vessels (n=53). Lipid parameters were determined by routine laboratory methods.
      Plasma malondialdehyde and vitamin E concentrations were determined with the high
      performance liquid chromatography. Other oxidant and antioxidant parameters were
      studied spectrophotometrically. RESULTS: While plasma malondialdehyde levels, the
      susceptibilities of erythrocyte and apolipoprotein B containing lipoproteins to
      in vitro induced oxidative stress, serum protein carbonyls, low density
      lipoprotein-cholesterol, triglyceride, apolipoprotein B and lipoprotein (a)
      levels had significantly increased, high-density lipoprotein-cholesterol and
      apolipoprotein AI levels, erythrocyte glutathione peroxidase, glutathione
      reductase, glucose 6 phosphate dehydrogenase, serum catalase, paraoxonase and
      arylesterase activities, plasma vitamin E and C and carotenoid levels had
      significantly decreased. The odds ratios for one-, two-, and three-vessel disease
      increased across especially higher tertiles of concentrations for oxidation
      parameters and lower tertiles of concentrations for antioxidant parameters.
      CONCLUSIONS: According to the results, we suggest that increased lipid and
      protein oxidation products and decreased antioxidant enzymes and vitamins
      contribute to increased oxidative stress which in turn is related to the severity
      of the disease.

PMID- 16600206
TI  - Basidiomycete cryopreservation on perlite: evaluation of a new method.
AB  - A new cryopreservation method using perlite as a carrier was evaluated on a large
      set of mycelial cultures of basidiomycetes. The viability and some other
      characteristics--growth, macro- and micromorphology, and laccase production--of
      442 strains were tested after 48-h and then after 3-year storage in liquid
      nitrogen using a perlite protocol (PP). All (100%) of them survived successfully
      both 48-h storage and 3-year storage in liquid nitrogen without noticeable growth
      and morphological changes. Also laccase production was unchanged. The viability
      and laccase production of a part (250) of these strains were compared with those
      of the strains subjected to an original agar plug protocol (OP). Using OP, 144
      strains (57.6%) out of 250 survived a 3-year storage in liquid nitrogen. The
      results indicate that the cryopreservation protocol used significantly influences
      survival of the strains. Markedly better results were achieved using the PP.

PMID- 16600207
TI  - Extra- and intra-cellular ice formation in Stage I and II Xenopus laevis oocytes.
AB  - We are currently investigating factors that influence intracellular ice formation
      (IIF) in mouse oocytes and oocytes of the frog Xenopus. A major reason for
      choosing these two species is that while their eggs normally do not possess
      aquaporin channels in their plasma membranes, these channels can be made to
      express. We wish to see whether IIF is affected by the presence of these
      channels. The present Xenopus study deals with control eggs not expressing
      aquaporins. The main factor studied has been the effect of a cryoprotective agent
      [ethylene glycol (EG) or glycerol] and its concentration. The general procedure
      was to (a) cool the oocytes on a cryostage to slightly below the temperatures at
      which extracellular ice formation occurs, (b) warm them to just below the melting
      point, and (c) then re-cool them to -50 degrees C at 10 degrees C/min. In the
      majority of cases, IIF occurs well into step (c), but a sizeable minority undergo
      IIF in steps (a) or (b). The former group we refer to as low-temperature
      flashers; the latter as high-temperature flashers. IIF is manifested as abrupt
      blackening of the egg, which we refer to as "flashing." Observations on the
      Linkam cryostage are restricted to Stage I and II oocytes, which have diameters
      of 200 300 microm. In the absence of a cryoprotective agent, that is in frog
      Ringers, the mean flash temperature for the low-temperature freezers is -11.4
      degrees C, although a sizeable percentage flash at temperatures much closer to
      that of the EIF (-3.9 degrees C). When EG is present, the flash temperature for
      the low-temperatures freezers drops significantly to approximately -20 degrees C
      for EG concentrations ranging from 0.5 to 1.5 M. The presence of 1.5 M glycerol
      also substantially reduces the IIF temperature of the low-temperature freezers;
      namely, to -29 degrees C, but 0.5 and 1 M glycerol exert little or no effect. The
      IIF temperatures observed using the Linkam cryostage agree well with those
      estimated by calorimetry [F.W. Kleinhans, J.F. Guenther, D.M. Roberts, P. Mazur,
      Analysis of intracellular ice nucleation in Xenopus oocytes by differential
      scanning calorimetry, Cryobiology 52 (2006) 128-138]. The IIF temperatures in
      Xenopus are substantially higher than those observed in mouse oocytes [P. Mazur,
      S. Seki, I.L. Pinn, F.W. Kleinhans, K. Edashige, Extra- and intracellular ice
      formation in mouse oocytes, Cryobiology 51 (2005) 29-53]. Perhaps that is a
      reflection of their much larger size.

PMID- 16600208
TI  - Alphabet, a Ser/Thr phosphatase of the protein phosphatase 2C family, negatively
      regulates RAS/MAPK signaling in Drosophila.
AB  - Signal transduction through the RAS/mitogen-activated protein kinase (MAPK)
      pathway depends on a diverse collection of proteins regulating positively and
      negatively signaling flow. We previously conducted a genetic screen in Drosophila
      to identify novel components of this signaling pathway. Here, we present the
      identification and characterization of a new gene, alphabet (alph), whose
      activity negatively regulates RAS/MAPK-dependent developmental processes in
      Drosophila and this, at a step downstream or in parallel to RAS. alph encodes a
      protein phosphatase 2C (PP2C) family member closely related to the mammalian PP2C
      alpha and beta isoforms. Interestingly, although alph gene product does not
      appear to be essential for viability, its elimination leads to weak but
      significant developmental defects reminiscent of an overactivated RAS/MAPK
      pathway. Consistent with this interpretation, strong genetic interactions are
      observed between alph alleles and mutations in bona fide components of the
      pathway. Together, this work identifies a PP2C of the alpha/beta subfamily as a
      novel negative regulator of the RAS/MAPK pathway and suggests that these
      evolutionarily conserved enzymes play a similar role in other metazoans. Finally,
      despite the relatively large size of the PP2C gene family in metazoans, this
      study represents only the second genetic characterization of a PP2C in these
      organisms.

PMID- 16600209
TI  - The effect of mGlu5 receptor positive allosteric modulators on signaling
      molecules in brain slices.
AB  - Positive allosteric modulators of metabotropic glutamate receptor subtype 5
      (mGlu5) have promising therapeutic potential. The effects of selective mGlu5
      receptor positive allosteric modulators on signaling molecules in brain slices
      have not been previously reported. The current study demonstrated that the
      selective mGlu5 receptor positive allosteric modulator, N-{4-chloro-2-[(1,3-dioxo
      1,3-dihydro-2H-isoindol-2yl)-methyl]phenyl}-2-hydrobenzamide (CPPHA) potentiated
      the response to a subthreshold concentration of 3,5-dihydroxy-phenylglycine
      (DHPG) on extracellular signal-regulated protein kinase (ERK) and cyclic-AMP
      responsive element-binding protein (CREB) activity, as well as N-methyl d
      aspartate (NMDA) receptor subunit NR1 phosphorylation in cortical and hippocampal
      slices. These results suggest that allosteric modulators of mGlu5 receptor could
      have physiologically significant effects by potentiating the actions of
      glutamate.

PMID- 16600210
TI  - Differential effects of selective and non-selective inhibition of nitric oxide
      synthase on the expression and activity of cyclooxygenase-2 during gastric ulcer
      healing.
AB  - Nitric oxide synthases (NOS) and cyclooxygenase-2 (COX-2) are important enzymes
      involved in ulcer healing but interactions between them have not been clearly
      defined. The aim of this study was to investigate the effects of selective or non
      selective inhibition of NOS on the expression and activity of COX-2 during
      healing of acetic acid-induced gastric ulcers in rats. N-[3-(aminomethyl)benzyl]
      acetamidine (1400 W), a potent selective inhibitor of inducible nitric oxide
      synthase (iNOS), at a dose of 0.1 mg/kg/day, was found to reduce the ulcer sizes
      at day 3 and 7 post-ulcer induction. On the other hand, 15 mg/kg/day of NG-nitro
      L-arginine methyl ester (L-NAME), a non-selective NOS inhibitor that suppresses
      both iNOS and endothelial nitric oxide synthase (eNOS), enlarged the ulcer sizes
      over the same time periods. The expression of COX-2 and COX activity, together
      with NF-kappaB activation in the ulcer tissues were down-regulated by L-NAME but
      not 1400 W. It is concluded that iNOS may contribute to ulcer formation while COX
      2 and eNOS promote ulcer healing. eNOS enhances COX-2 expression possibly through
      the activation of NF-kappaB.

PMID- 16600211
TI  - Bioactive 1,4-dihydroisonicotinic acid derivatives prevent oxidative damage of
      liver cells.
AB  - 1,4-Dihydroisonicotinic acid derivatives (1,4-DHINA) are compounds closely
      related to derivatives of 1,4-dihydropyridine, a well-known calcium channel
      antagonists. 1,4-DHINA we used were derived from a well-known antioxidant
      Diludin. Although some compounds have neuromodulatory or antimutagenic
      properties, their activity mechanisms are not well known. This study was
      performed to obtain data on antioxidant and bioprotective activities of: 2,6
      dimethyl-3,5-diethoxycarbonyl-1,4-dihydroisonicotinic acid (Ia); sodium 2-(2,6
      dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)glutamate (Ib)
      and sodium 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4
      carboxamido)ethane-sulphate (Ic). 1,4-DHINA's activities were studied in
      comparison to Trolox by: N,N-Diphenyl-N'-picrylhydrazyl (DPPH*), deoxyribose
      degradation, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium
      salt (ABTS) radical scavenging and antioxidative capacity assays; copper-induced
      lipid peroxidation of cultured rat liver cells (malondialdehyde determination by
      high performance liquid chromatography and 4-hydroxynonenal-protein conjugates by
      dot-blot); (3)H-thymidine incorporation and trypan blue assay for liver cells
      growth and viability. In all assays used Ia was the most potent antioxidant. Ia
      was also a potent antioxidant at non-toxic concentrations for liver cell
      cultures. It completely abolished, while Ic only slightly decreased copper
      induced lipid peroxidation of liver cells. Thus, antioxidant capacities are
      important activity principle of Ia, which was even superior to Trolox in the cell
      cultures used, while activity principles of Ic and Ib remain yet to be
      determined.

PMID- 16600212
TI  - A dual function for Deep orange in programmed autophagy in the Drosophila
      melanogaster fat body.
AB  - Lysosomal degradation of cytoplasm by way of autophagy is essential for cellular
      amino acid homeostasis and for tissue remodeling. In insects such as Drosophila,
      autophagy is developmentally upregulated in the larval fat body prior to
      metamorphosis. Here, autophagy is induced by the hormone ecdysone through down
      regulation of the autophagy-suppressive phosphoinositide 3-kinase (PI3K)
      signaling pathway. In yeast, Vps18 and other members of the HOPS complex have
      been found essential for autophagic degradation. In Drosophila, the Vps18
      homologue Deep orange (Dor) has previously been shown to mediate fusion of
      multivesicular endosomes with lysosomes. A requirement of Dor for ecdysone
      mediated chromosome puffing has also been reported. In the present report, we
      have tested the hypothesis that Dor may control programmed autophagy at the level
      of ecdysone signaling as well as by mediating autophagosome-to-lysosome fusion.
      We show that dor mutants are defective in programmed autophagy and provide
      evidence that autophagy is blocked at two levels. First, PI3K activity was not
      down-regulated correctly in dor larvae, which correlated with a decrease in
      ecdysone reporter activity. The down-regulation of PI3K activity was restored by
      feeding ecdysone to the mutant larvae. Second, neither exogenous ecdysone nor
      overexpression of PTEN, a silencer of PI3K signaling, restored fusion of
      autophagosomes with lysosomes in the fat body of dor mutants. These results
      indicate that Dor controls autophagy indirectly, via ecdysone signaling, as well
      as directly, via autolysosomal fusion.

PMID- 16600213
TI  - Spindle checkpoint function requires Mad2-dependent Cdc20 binding to the Mad3
      homology domain of BubR1.
AB  - The mitotic spindle assembly checkpoint delays anaphase until all chromosomes
      achieve bipolar attachment to the spindle microtubules. The spindle assembly
      checkpoint protein BubR1 is thought to act by forming an inhibitory complex with
      Cdc20. We here identify two Cdc20 binding sites on BubR1. A strong Cdc20 binding
      site is located between residues 490 and 560, but mutations that disrupt Cdc20
      binding to this region have no effect upon checkpoint function. A second Cdc20
      binding site present between residues 1 and 477 is highly specific for Cdc20
      already bound to Mad2. Mutation of a conserved lysine in this region weakened
      Cdc20 binding and correspondingly reduced checkpoint function. Our results
      indicate that there may be more than one checkpoint complex containing BubR1,
      Mad2, and Cdc20. They also lead us to propose that in vivo checkpoint inhibition
      of Cdc20 is a two-step process in which prior binding of Mad2 to Cdc20 is
      required to make Cdc20 sensitive to inhibition by BubR1. Thus, Mad2 and BubR1
      must cooperate to inhibit Cdc20 activity.

PMID- 16600214
TI  - Normalizing the bone marrow microenvironment with p38 inhibitor reduces multiple
      myeloma cell proliferation and adhesion and suppresses osteoclast formation.
AB  - The multiple myeloma (MM) bone marrow (BM) microenvironment plays a critical role
      in supporting tumor growth and survival as well as in promoting formation of
      osteolytic lesions. Recent results suggest that the p38 mitogen-activated protein
      kinase (MAPK) is an important factor in maintaining this activated environment.
      In this report, we demonstrate that the p38alpha MAPK inhibitor, SCIO-469,
      suppresses secretion of the tumor-supportive factors IL-6 and VEGF from BM
      stromal cells (BMSCs) as well as cocultures of BMSCs with MM cells, resulting in
      reduction in MM cell proliferation. Additionally, we show that SCIO-469 prevents
      TNFalpha-induced adhesion of MM cells to BMSCs through an ICAM-1- and VCAM-1
      independent mechanism. Microarray analysis revealed a novel set of TNFalpha
      induced chemokines in BMSCs that is strongly inhibited by SCIO-469. Furthermore,
      reintroduction of chemokines CXCL10 and CCL8 to BMSCs overcomes the inhibitory
      effect of SCIO-469 on TNFalpha-induced MM adhesion. Lastly, we show that SCIO-469
      inhibits secretion and expression of the osteoclast-activating factors IL-11,
      RANKL, and MIP-1alpha as well as prevents human osteoclast formation in vitro.
      Collectively, these results suggest that SCIO-469 treatment can suppress factors
      in the bone marrow microenvironment to inhibit MM cell proliferation and adhesion
      and also to alleviate osteolytic activation in MM.

PMID- 16600215
TI  - NOV/CCN3 impairs muscle cell commitment and differentiation.
AB  - NOV (nephroblastoma overexpressed) is a member of a family of proteins which
      encodes secreted matrix-associated proteins. NOV is expressed during development
      in dermomyotome and limb buds, but its functions are still poorly defined. In
      order to understand the role of NOV in myogenic differentiation, C2C12 cells
      overexpressing NOV (C2-NOV) were generated. These cells failed to engage into
      myogenic differentiation, whereas they retained the ability to differentiate into
      osteoblasts. In differentiating conditions, C2-NOV cells remained proliferative,
      failed to express differentiation markers and lost their ability to form
      myotubes. Inhibition of differentiation by NOV was also observed with human
      primary muscle cells. Further examination of C2-NOV cells revealed a strong
      downregulation of the myogenic determination genes MyoD and Myf5 and of IGF-II
      expression. MyoD forced expression in C2-NOV was sufficient to restore
      differentiation and IGF-II induction whereas 10(-6) M insulin treatment had no
      effects. NOV therefore acts upstream of MyoD and does not affect IGF-II induction
      and signaling. HES1, a target of Notch, previously proposed to mediate NOV
      action, was not implicated in the inhibition of differentiation. We propose that
      NOV is a specific cell fate regulator in the myogenic lineage, acting negatively
      on key myogenic genes thus controlling the transition from progenitor cells to
      myoblasts.

PMID- 16600216
TI  - Focus on molecules: retinoschisin (RS1).

PMID- 16600217
TI  - Boophilus microplus: its saliva contains microphilin, a small thrombin inhibitor.
AB  - Saliva of the cattle tick Boophilus microplus contains two thrombin inhibitors,
      BmAP and microphilin. This work presents the purification and characterization of
      microphilin. It was purified from the saliva by gel filtration, ultrafiltration
      through a 3 kDa cut-off membrane and affinity chromatography in a thrombin
      Sepharose column. Analysis by mass spectrometry showed a molecular mass of 1770
      Da. Microphilin is the smallest salivary thrombin inhibitor peptide known to
      date. It inhibits fibrinocoagulation and thrombin-induced platelet aggregation
      with an IC(50) of 5.5 microM, is temperature resistant and its inhibitory
      activity was abolished by protease K treatment. Microphilin did not inhibit the
      amidolytic activity of the enzyme upon a small chromogenic substrate, but
      inhibited the hydrolysis of a substrate that binds both catalytic site and
      exosite I. Therefore, we propose that microphilin blocks thrombin at exosite I.

PMID- 16600218
TI  - Trichinella spiralis: histamine secretion induced by TSL-1 antigens from
      unsensitized mast cells.
AB  - Mast cells' hyperplasia and activation are prominent features in Trichinella
      spiralis infection. Recently, it was shown that TSL-1 antigens from T. spiralis
      muscle larvae induce IL-4 and TNF release by unsensitized, normal mast cells (MC)
      involving an Ig-independent mechanism. In this study, we characterized histamine
      secretion induced by TSL-1 antigens from normal, unsensitized rat peritoneal MC.
      Maximum histamine secretion (30+/-5.3% SEM, n=13) was achieved with 30 ng/mL TSL
      1 antigens. However, TSL-1 did not induce an increase in beta-hexosaminidase
      release or NADPH oxidase activity by MC. Interestingly, histamine secretion by
      TSL-1 was completed at 10s, and was inhibited by both Bordetella pertussis toxin
      and neuraminidase V, characteristics similar to those involved in substance P
      induced histamine secretion. However, in contrast to substance P, TSL-1 induced
      histamine secretion in the absence of detectable changes in intracellular Ca(2+).
      We are investigating the molecular pathways involved in MC activation by TSL-1.

PMID- 16600219
TI  - Anisakis simplex: CO(2)-fixing enzymes and development throughout the in vitro
      cultivation from third larval stage to adult.
AB  - We studied the effect of CO(2) on the in vitro cultivation of Anisakis simplex,
      an aquatic parasitic nematode of cetaceans (final hosts) and fish, squid,
      crustaceans and other invertebrates (intermediate/paratenic hosts), and,
      occasionally, of man (accidental host). The results showed that a high pCO(2), at
      a suitable temperature, is vital for the optimum development of these nematodes,
      at least from the third larval stage (L3) to adult. After 30 days cultivation in
      air, molting to L4 (fourth larval stage) was reduced to 1/3, while survival was
      about 1/3 of that when cultivated in air + 5% CO(2). The activity of the CO(2)
      fixing enzymes, PEPCK and PEPC, was also studied. Throughout the development of
      the worms studied, PEPCK activity was much higher than that of PEPC (e.g., 305
      vs. 6.8 nmol/min.mg protein, respectively, in L3 collected from the host fish).
      The activity of these enzymes in the worms cultivated in air + 5% CO(2) was
      highest during M3, and was also generally higher than that of those cultivated in
      air only, especially during molting from L3 to L4 (e.g., in recently molted L4,
      PEPCK activity was 3.7 times greater than that of PEPC 2.9 times greater than
      when cultivated in air).

PMID- 16600220
TI  - Acupuncture and infertility: we need to stick to good science.
AB  - The research published to date does not show a definitive positive impact of
      acupuncture on IVF success rates. However, researchers seem to lack traditional
      scientific practices when interpreting the data.

PMID- 16600221
TI  - The play of chance.
AB  - Most randomized controlled trials are small relative to the clinical question
      they address, and chance causes more variability in the results of small trials.
      Thus, when small studies herald new treatment interventions, clinicians might
      wish to wait until the body of evidence is weighty and consistent enough to be
      convincing.

PMID- 16600223
TI  - Acupuncture as adjunctive therapy in assisted reproduction: remaining
      uncertainties.
AB  - Two randomized trials provide suggestive evidence that acupuncture might be an
      effective adjunctive therapy in assisted reproductive technologies, leading to
      improved pregnancy rates. However, additional research addressing remaining
      scientific and methodologic issues is needed before routine use of acupuncture
      can be recommended.

PMID- 16600222
TI  - Carnitine for the treatment of idiopathic asthenospermia: a randomized, double
      blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine the effect of oral carnitine supplementation on the semen
      parameters of men with idiopathic asthenospermia. DESIGN: Prospective,
      randomized, double-blind placebo-controlled study. SETTING: Academic tertiary
      referral centers. PATIENT(S): Male patients presenting with infertility and with
      sperm motility of 10%-50% were selected. INTERVENTION(S): Patients were
      randomized to 24-week treatment arms of oral carnitine (2,000 mg L-carnitine and
      1,000 mg L-acetyl-carnitine per day) or placebo. MAIN OUTCOME MEASURE(S): Sperm
      motility and total motile sperm counts at baseline, 12 weeks, and 24 weeks.
      Seminal plasma and sperm free, acetyl, and total L-carnitine levels at baseline
      and at week 24. RESULT(S): Twenty-one patients entered the study, with 12
      patients in the carnitine arm and 9 in the placebo arm. There were no significant
      differences in baseline semen parameters between the carnitine and placebo arms.
      There was no statistically significant or clinically significant increase in
      motility or total motile sperm counts between baseline, 12 week, or 24 weeks in
      the carnitine or placebo arms. CONCLUSION(S): Carnitine supplementation
      demonstrated no clinically or statistically significant effect on sperm motility
      or total motile sperm counts in men with idiopathic asthenospermia.

PMID- 16600224
TI  - Association of lower plasma estradiol levels and low expression of scavenger
      receptor class B, type I in infertile women.
AB  - OBJECTIVE: To determine the expression of the scavenger receptor, class B, type I
      (SR-BI) in human granulosa cells. DESIGN: Prospective cohort analysis. SETTING:
      Tertiary academic university hospital. PATIENT(S): Women undergoing IVF
      treatment. INTERVENTION(S): Granulosa cells were isolated from oocyte retrievals.
      MAIN OUTCOME MEASURE(S): Total RNA and cell lysates were isolated from the
      granulosa cells, and SR-BI RNA and protein expression were quantified by real
      time polymerase chain reaction and western blotting, respectively. Baseline and
      peak E2 levels were drawn before IVF treatment and before hCG stimulation.
      RESULT(S): The expression of SR-BI RNA and protein were positively correlated.
      The prevalence of low SR-BI RNA expression (defined as below 25th percentile) was
      26%, whereas the prevalence of high SR-BI expression (defined as above 75th
      percentile) was 24%. Expression of SR-BI RNA was not correlated with body mass
      index, age, race or ethnicity, primary diagnosis of infertility, or pregnancy
      outcomes. However, baseline and peak E2 levels were significantly lower in
      subjects with low SR-BI RNA expression as compared with subjects with high SR-BI
      expression (P<.04). There was a positive correlation between the number of
      retrieved (P<.02) and fertilized oocytes (P<.002) and SR-BI RNA levels.
      CONCLUSION(S): Scavenger receptor-BI is expressed in human granulosa cells.
      Subjects with low SR-BI expression had lower baseline and peak E2 levels and
      lower number of retrieved and fertilized oocytes.

PMID- 16600225
TI  - Influence of acupuncture stimulation on pregnancy rates for women undergoing
      embryo transfer.
AB  - OBJECTIVE: To evaluate the effects of acupuncture on clinical pregnancy rates for
      women undergoing ET. DESIGN: Single-blind, randomized controlled trial using a
      noninvasive sham acupuncture control. SETTING: Repromed, The Reproductive
      Medicine Unit of The University of Adelaide. PATIENT(S): Women undergoing IVF.
      INTERVENTION(S): Women were randomly allocated to acupuncture or noninvasive sham
      acupuncture with the placebo needle. All women received three sessions, the first
      undertaken on day 9 of stimulating injections, the second before ET, and the
      third immediately after ET. MAIN OUTCOME MEASURE(S): The primary outcome was
      pregnancy. Secondary outcomes were implantation, ongoing pregnancy rate at 18
      weeks, adverse events, and health status. RESULT(S): Two hundred twenty-eight
      subjects were randomized. The pregnancy rate was 31% in the acupuncture group and
      23% in the control group. For those subjects receiving acupuncture, the odds of
      achieving a pregnancy were 1.5 higher than for the control group, but the
      difference did not reach statistical significance. The ongoing pregnancy rate at
      18 weeks was higher in the treatment group (28% vs. 18%), but the difference was
      not statistically significant. CONCLUSION(S): There was no significant difference
      in the pregnancy rate between groups; however, a smaller treatment effect can not
      be excluded. Our results suggest that acupuncture was safe for women undergoing
      ET.

PMID- 16600226
TI  - Urinary follicle-stimulating hormone (FSH) is more effective than recombinant FSH
      in older women in a controlled randomized study.
AB  - OBJECTIVE: The following study was conducted to determine which FSH, recombinant
      or urinary, works better in older women. DESIGN: We conducted a controlled
      randomized study in a single university IVF center. SETTING: University IVF
      center. PATIENT(S): Women (N = 257) over 39 years old undergoing IVF.
      INTERVENTION(S): The patients were randomized into two study groups at their
      first IVF cycle: 121 patients were treated with recombinant FSH, and 120 patients
      were treated with urinary FSH. Both groups were suppressed with a long GnRH
      analog protocol. MAIN OUTCOME MEASURE(S): Days of stimulation, E2 at the day of
      hCG, total amount of FSH administered, number of oocytes collected, amount of FSH
      per oocyte, and number of embryos obtained. RESULT(S): Patients treated with
      urinary FSH required a significantly lower total amount of FSH, and a lower
      amount of FSH per oocyte than women treated with recombinant FSH. The other
      measures evaluated did not show any statistically significant differences.
      CONCLUSION(S): Our study showed that urinary FSH performed better in older women
      than recombinant FSH when associated with the long protocol.

PMID- 16600227
TI  - Use of a medium buffered with N-hydroxyethylpiperazine-N-ethanesulfonate (HEPES)
      in intracytoplasmic sperm injection procedures is detrimental to the outcome of
      in vitro fertilization.
AB  - OBJECTIVE: This study was conducted to determine whether N-hydroxyethylpiperazine
      N-ethanesulfonate (HEPES)-buffered medium used for the microinjection of sperm
      into oocytes may be detrimental for the embryo. DESIGN: Controlled randomized
      study. SETTING: Private IVF center. PATIENT(S): Women (n = 708) undergoing ICSI.
      INTERVENTION(S): The women were randomized into two study groups: 2,204 oocytes
      from 357 women were treated using a medium buffered with bicarbonate without
      HEPES during the ICSI procedure, and 2,168 oocytes from 351 women were treated
      using a medium buffered with HEPES during the ICSI procedure. MAIN OUTCOME
      MEASURE(S): Fertilization rate, degeneration rate, triploid rate, cleavage rate,
      embryo quality, pregnancy rate, implantation rate, and abortion rate. RESULT(S):
      Oocytes treated with a HEPES-buffered medium showed a statistically significant
      higher rate of triploid and degenerated oocytes after fertilization with ICSI
      compared with oocytes treated with a medium without HEPES. The embryos obtained
      from oocytes microinjected with a HEPES-buffered medium showed a statistically
      significant higher rate of highly fragmented embryos compared with the controls.
      Pregnancy rate and implantation rate were statistically significantly lower in
      the patient group with oocytes treated with the HEPES-buffered medium. The other
      parameters evaluated did not show any statistically significant differences.
      CONCLUSION(S): Our study showed that the use of media buffered with HEPES, during
      the microinjection of sperm into the oocytes, is detrimental for IVF outcome and
      should be avoided.

PMID- 16600228
TI  - Multifollicular ovaries in female adolescents with cystic fibrosis.
AB  - OBJECTIVE: To assess hormonal status and morphology of ovaries in cystic fibrosis
      (CF) adolescents. DESIGN: Prospective study. SETTING: University teaching
      hospital. PATIENT(S): Female adolescents: 18 with CF and 18 normal.
      INTERVENTION(S): Transabdominal pelvic ultrasonography and venipuncture. MAIN
      OUTCOME MEASURE(S): Hormone profile and ultrasound examination of ovaries and
      uterus. RESULT(S): Levels of LH, LH/FSH, androstenedione, and PRL were
      significantly higher in the CF adolescents. Levels of sex hormone-binding
      globulin (SHBG) were significantly lower and had negative correlation with
      percentage of body fat. Percentage of body fat and body mass index were
      significantly lower in CF and had significant correlation. Levels of E2, FSH, T,
      and DHEAS were comparable in the two groups. Ultrasound revealed cysts in eight
      (44%) of the CF subjects; six of these had LH/FSH >3, and three had been operated
      for ovarian torsion. Nine out of all of the CF subjects (50%) had DM. No obesity,
      hirsutism, or acne was observed. The Shwachman score was 87.44 +/- 4.83 and
      correlated significantly with the percentage of body fat. CONCLUSION(S):
      Multifollicular ovaries were frequent in CF adolescents. Hormone changes
      characteristic of polycystic ovary syndrome were detected. The low T levels,
      despite low SHBG, and the absence of hirsutism or acne may be a result of a lower
      percentage of body fat, disturbances at the pilosebaceous-adipocyte endocrine
      unit, or mechanical or other causes.

PMID- 16600229
TI  - Hysteroscopic metroplasty of the complete uterine septum, duplicate cervix, and
      vaginal septum.
AB  - OBJECTIVE: To determine if sectioning of the cervical septum in hysteroscopic
      metroplasty of the complete uterine septum is associated with intraoperative
      bleeding, cervical incompetence, and secondary infertility. DESIGN: Multicenter,
      randomized, controlled clinical trial. SETTING: University hospitals. PATIENT(S):
      Twenty-eight women with a diagnosis of complete uterine septum who had a history
      of pregnancy wastage or infertility. They were randomized into two groups: group
      A underwent metroplasty including section of the cervical septum; group B
      underwent the same procedure with preservation of the cervical septum.
      INTERVENTION(S): Hysteroscopic metroplasty was performed for all patients in the
      two groups. MAIN OUTCOME MEASURE(S): Operating time, distending media deficit,
      total distending media used, intraoperative bleeding, complications, and
      reproductive outcome. RESULT(S): Operating times were 36.40 +/- 10.67 minutes and
      73 +/- 14.40 minutes in group A and group B, respectively. Distending media
      deficit was 456.66 +/- 165.68 mL in group A, while in group B it was 673.84 +/-
      220.36. Two cases of pulmonary edema and three cases of significant bleeding (>
      150 mL) were seen in group B. The cesarean section rate was significantly higher
      in group B. There were no significant differences in the reproductive outcome in
      the two groups. CONCLUSION(S): Resection of the cervical septum during
      hysteroscopic metroplasty of complete uterine septum makes the procedure safer,
      easier, and less complicated than the procedure with preservation of the cervical
      septum. This procedure is recommended for all cases of complete uterine septum.

PMID- 16600231
TI  - Expression of mannose-binding lectin in the peritoneal fluid of women with and
      without endometriosis.
AB  - Mannose-binding lectin (MBL) modulates inflammation and usually enhances
      clearance of apoptotic cells. We observed that the concentration and total amount
      of peritoneal fluid MBL does not differ in patients with and without
      endometriosis.

PMID- 16600232
TI  - Acupuncture on the day of embryo transfer significantly improves the reproductive
      outcome in infertile women: a prospective, randomized trial.
AB  - OBJECTIVE: To evaluate the effect of acupuncture on reproductive outcome in
      patients treated with IVF/intracytoplasmic sperm injection (ICSI). One group of
      patients received acupuncture on the day of ET, another group on ET day and again
      2 days later (i.e., closer to implantation day), and both groups were compared
      with a control group that did not receive acupuncture. DESIGN: Prospective,
      randomized trial. SETTING: Private fertility center. PATIENT(S): During the study
      period all patients receiving IVF or ICSI treatment were offered participation in
      the study. On the day of oocyte retrieval, patients were randomly allocated (with
      sealed envelopes) to receive acupuncture on the day of ET (ACU 1 group, n = 95),
      on that day and again 2 days later (ACU 2 group, n = 91), or no acupuncture
      (control group, n = 87). INTERVENTION(S): Acupuncture was performed immediately
      before and after ET (ACU 1 and 2 groups), with each session lasting 25 minutes;
      and one 25-minute session was performed 2 days later in the ACU 2 group. MAIN
      OUTCOME MEASURE(S): Clinical pregnancy and ongoing pregnancy rates in the three
      groups. RESULT(S): Clinical and ongoing pregnancy rates were significantly higher
      in the ACU 1 group as compared with controls (37 of 95 [39%] vs. 21 of 87 [26%]
      and 34 of 95 [36%] vs. 19 of 87 [22%]). The clinical and ongoing pregnancy rates
      in the ACU 2 group (36% and 26%) were higher than in controls, but the difference
      did not reach statistical difference. CONCLUSION(S): Acupuncture on the day of ET
      significantly improves the reproductive outcome of IVF/ICSI, compared with no
      acupuncture. Repeating acupuncture on ET day +2 provided no additional beneficial
      effect.

PMID- 16600233
TI  - Polymorphisms of the peroxisome proliferator-activated receptor-gamma and its
      coactivator-1alpha genes in Chinese women with polycystic ovary syndrome.
AB  - The polymorphisms of the peroxisome proliferator-activated receptor-gamma
      (Pro12Ala) and its coactivator-1 (Gly482Ser) genes were investigated among 201
      Chinese Han women with polycystic ovary syndrome (PCOS) and among 147 regularly
      cycling women as control subjects. We did not find statistically significant
      differences with peroxisome proliferator-activated receptor-gamma2 Pro12Ala and
      peroxisome proliferator-activated receptor-gamma-1alpha Gly482Ser polymorphism
      distributions between Chinese women with PCOS and controls, or with body mass
      index and reproductive hormones among various genotypic groups of PCOS,
      suggesting that these genetic mutants did not have an effect on the
      susceptibility to PCOS.

PMID- 16600234
TI  - The psychobiology and diagnostic significance of amenorrhea in patients with
      anorexia nervosa.
AB  - Amenorrhea is a diagnostic criterion for anorexia nervosa (AN), although
      menstrual cycles have been found to persist in some women with all the other
      features of AN. This study sought to determine factors that are associated with
      amenorrhea in 39 women with current primary spectrum AN. The use of exercise to
      control weight (odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.3-9.9; P
      = .02), low novelty seeking scores (OR = 0.7; 95% CI = 0.58-0.94; P = .02), and
      low systolic blood pressure (OR = 0.9; 95% CI = 0.84-0.99; P = .046) were
      predictors of amenorrhea independent of body mass index.

PMID- 16600235
TI  - Past oral contraceptive use and angiographic coronary artery disease in
      postmenopausal women: data from the National Heart, Lung, and Blood Institute
      sponsored Women's Ischemia Syndrome Evaluation.
AB  - OBJECTIVE: To evaluate past oral contraceptive use and angiographic coronary
      artery disease in women. SETTING: Academic medical centers. PATIENT(S): Six
      hundred seventy-two postmenopausal women enrolled in the Women's Ischemia
      Syndrome Evaluation (WISE) with coronary risk factors undergoing coronary
      angiography for suspected myocardial ischemia. INTERVENTION(S): Past oral
      contraceptive use, assessed by reproductive questionnaire. MAIN OUTCOME
      MEASURE(S): Quantitative coronary artery disease, assessed by a core angiography
      laboratory. RESULT(S): Past oral contraceptive use was associated with a lower
      mean coronary artery disease severity index score (mean +/- SD: 11.8 +/- 10.3 vs.
      18.7 +/- 17.3) compared with non-prior users, despite age adjustment. Past oral
      contraceptive use remained a significant independent negative predictor of
      coronary artery disease severity when adjusting for coronary risk factors,
      including age, diabetes mellitus, triglycerides, low-density lipoprotein
      cholesterol, smoking, aspirin use, and lipid-lowering medication (model R2 =
      0.19). The modeling indicated that past oral contraceptive use was associated
      with a 2.44 lower coronary artery disease severity score index. There was no
      apparent relationship between duration of past oral contraceptive use and the
      coronary artery disease severity index score. CONCLUSION(S): Past oral
      contraceptive use is associated with less coronary artery disease, measured by
      quantitative coronary angiography, among postmenopausal women with suspected
      myocardial ischemia. These findings suggest that a prospective study should
      address the hypothesis that past oral contraceptive use during the premenopausal
      years might offer women protection from atherosclerotic coronary disease later in
      life.

PMID- 16600236
TI  - Hominin first metatarsals (SKX 5017 and SK 1813) from Swartkrans: a morphometric
      analysis.
AB  - Two hominin metatarsals from Swartkrans, SKX 5017 and SK 1813, have been reported
      by Susman and Brain [1988. New first metatarsal (SKX 5017) from Swartkrans and
      the gait of Paranthropus robustus. Am. J. Phys. Anthropol. 79, 451-454] and
      Susman and de Ruiter [2004. New hominin first metatarsal (SK 1813) from
      Swartkrans. J. Hum. Evol. 47, 171-181]. They found these bones to have both
      primitive and derived traits indicating that, while being bipedal, these
      hominines had a unique toe-off mechanism. We have undertaken additional
      multivariate morphometric analyses, comparing the fossils to the first
      metatarsals of modern humans and extant apes. The largest proportion of
      discrimination lies in the different locomotor functions: apes on the one hand
      and the humans and fossils on the other. While the fossils have the closest
      affinity to humans, they have a unique biomechanical pattern suggesting a more
      facultative form of bipedalism. The implications of this are, while morphometric
      analyses do not necessarily directly capture the described primitive and derived
      traits, the associated functional pattern is held within the broader morphology
      of the bone.

PMID- 16600237
TI  - Ethical issues in medical education: gifts and obligations.

PMID- 16600238
TI  - Embryo research.

PMID- 16600239
TI  - Striking a balance--health experiences of male ambulance personnel with
      musculoskeletal symptoms: a grounded theory.
AB  - BACKGROUND: Musculoskeletal disorders (MSD) are a dominant cause to long-term
      sick leave and early retirement. Some occupational groups are more affected than
      others and ambulance personnel are among them. Despite a vast amount of research,
      only a small part focuses the experiences of the affected. OBJECTIVES: The aim of
      the study was to explore the experience of illness and wellness in ambulance
      personnel with musculoskeletal symptoms. DESIGN: An emerging design was used in
      accordance with Grounded Theory. PARTICIPANTS: Informants in the study were ten
      men with musculoskeletal symptoms, working as ambulance personnel at an ambulance
      station located in a mid-sized city in Sweden. METHODS: Narrative interviews were
      performed, parallel to a constant comparative analysis. RESULTS: The study
      resulted in a model, which describes the experience of illness and wellness as
      characterised by an effort to strike a balance. Wellness through nurturing
      appeared parallel to encountering illness as an experience and a threat.
      Accepting and handling illness was of importance to maintaining wellness, and
      wellness through nurturing was the motivation for accepting and handling illness.
      CONCLUSIONS: Enhancing the understanding of wellness and illness makes it
      possible to avoid undermining the meaningfulness that support accepting and
      handling illness, and by understanding different aspects of illness prevention
      can become facilitated. This is of importance as other aspects than solely
      physical have shown to be similarly important in the development of MSD.

PMID- 16600240
TI  - Linkage disequilibrium between alleles at highly polymorphic mini- and micro
      satellite loci of Theileria parva isolated from cattle in three regions of Kenya.
AB  - Theileria parva schizont-infected lymphocyte culture isolates from western,
      central and coastal Kenya were analysed for size polymorphism at 30 T. parva
      specific variable number tandem repeat (VNTR) loci using a panel of mini- and
      micro-satellite markers. The mean number of alleles ranged from 3 to 11 at
      individual loci and 183 distinct alleles were observed in total, indicating high
      genetic diversity within the T. parva gene pool in Kenyan cattle. The frequency
      distribution of the length variation of specific alleles among isolates ranged
      from normal to markedly discontinuous. Genetic relationships between isolates
      were analysed using standard indices of genetic distance. Genetic distances and
      dendrograms derived from these using neighbour-joining algorithms did not
      indicate significant clustering on a geographical basis. Analysis of molecular
      variance demonstrated that the genetic variation between individual isolates was
      72%, but only 2.3% when isolates from different regions were pooled. Both these
      observations suggest minimal genetic sub-structuring relative to geographical
      origin. Linkage disequilibrium was observed between pairs of loci within
      populations, as in certain Ugandan T. parva populations. A novel observation was
      that disequilibrium was also detected between alleles at three individual pairs
      of VNTR loci when isolates from the three regional meta-populations were pooled
      for analysis.

PMID- 16600241
TI  - Pathogenic T cells in cerebral malaria.
AB  - Malaria remains a major global health problem and cerebral malaria (CM) is one of
      the most serious complications of this disease. Recent years have seen important
      advances in our understanding of the pathogenesis of cerebral malaria. Parasite
      sequestration, a hallmark of this syndrome, is thought to be solely responsible
      for the pathological process. However, this phenomenon cannot explain all aspects
      of the pathogenesis of CM. The use of an animal model, Plasmodium berghei ANKA in
      mice, has allowed the identification of specific pathological components of CM.
      Although multiple pathways may lead to CM, an important role for CD8+ T cells has
      been clarified. Other cells, including platelets, and mediators such as cytokines
      also have an important role. In this review we have focused on the role of T
      cells, and discuss what remains to be studied to understand the pathways by which
      these cells mediate CM.

PMID- 16600243
TI  - Harbouring in the brain: A focus on immune evasion mechanisms and their
      deleterious effects in malaria and human African trypanosomiasis.
AB  - Malaria and human African trypanosomiasis represent the two major tropical vector
      transmitted protozoan infections, displaying different prevalence and
      epidemiological patterns. Death occurs mainly due to neurological complications
      which are initiated at the blood-brain barrier level. Adapted host-immune
      responses present differences but also similarities in blood-brain
      barrier/parasite interactions for these diseases: these are the focus of this
      review. We describe and compare parasite evasion mechanisms, the initiating
      mechanisms of central nervous system pathology and major clinical and
      neuropathological features. Finally, we highlight the common immune mediated
      mechanisms leading to brain involvement. In both diseases neurological damage is
      caused mainly by cytokines (interferon-gamma, tumour necrosis factor-alpha and IL
      10), nitric oxide and endothelial cell apoptosis. Such a comparative analysis is
      expected to be useful in the comprehension of disease mechanisms, which may in
      turn have implications for treatment strategies.

PMID- 16600244
TI  - Proteolysis and Toxoplasma invasion.
AB  - Apicomplexan parasites including Toxoplasma gondii cause widespread human and
      animal diseases, often with the most severe manifestations involving the central
      nervous system. The need for new therapeutic agents along with the fascinating
      biology of these parasites has fueled a keen interest in understanding how key
      steps in the life cycle are regulated. Proteolysis is intimately associated with
      cell and tissue invasion by these obligate intracellular parasites and recent
      studies have begun to identify the proteases involved in these processes. Based
      on clues from inhibitor experiments and cleavage site mapping studies, several
      groups are using emerging genome information, chemical proteomics and molecular
      genetics to identify and validate proteases that regulate secretory organelle
      biogenesis and invasion protein activity. These studies are revealing roles for
      an assortment of proteases including cathepsins, subtilases and rhomboids in cell
      and tissue invasion. The identification of highly selective inhibitors for these
      proteases has the potential to not only further dissect their roles in infection
      but also to ameliorate disease.

PMID- 16600245
TI  - Cerebral malaria: role of microparticles and platelets in alterations of the
      blood-brain barrier.
AB  - Brain lesions of cerebral malaria (CM) are characterised by a sequestration of
      Plasmodium falciparum-parasitised red blood cells (PRBC), leucocytes and
      platelets within brain microvessels, by an excessive release of pro-inflammatory
      cytokines as well as by disruption of the blood-brain barrier (BBB). We evaluated
      the possibility that PRBC and platelets interact and induce functional
      alterations in brain endothelium. Using an in vitro model of endothelial lesion,
      we showed that platelets can act as bridges between PRBC and endothelial cells
      (EC) allowing the binding of PRBC to endothelium devoid of cytoadherence
      receptors. Furthermore, platelets potentiated the cytotoxicity of PRBC for brain
      EC by inducing an alteration of the integrity of their monolayer and increasing
      their apoptosis. These findings provide insights into the mechanisms by which
      platelets can be deleterious to the brain endothelium during CM. Another aspect
      of inflammatory and infectious diseases is that they often lead to activation of
      vascular and blood cells. Such activation results in an enhanced vesiculation,
      i.e. the release of circulating microparticles (MP). We thus explored plasma
      levels of endothelial MP in Malawian children with malaria. Plasma MP numbers
      were markedly increased on admission only in patients with severe malaria
      complicated with coma. Using the experimental mouse model of CM, we evaluated the
      pathogenic implications of MP using genetically deficient mice in which the
      capacity to vesiculate is impaired. Such mice, lacking the ABCA-1 gene, upon
      infection by Plasmodium berghei ANKA, showed complete resistance to CM. When
      purified from infected susceptible animals, MP were able to reduce normal plasma
      clotting time and to significantly enhance tumour necrosis factor release from
      naive macrophages. Altogether these data provide a novel insight into the
      pathogenic mechanisms leading to the neurological syndrome. The finding that ABCA
      1 gene deletion confers complete protection against cerebral pathology, linked to
      an impaired MP production, provides new potential targets for therapeutic
      amelioration of severe malaria.

PMID- 16600246
TI  - Gene expression and pharmacology of nematode NLP-12 neuropeptides.
AB  - This study examines the biology of NLP-12 neuropeptides in Caenorhabditis
      elegans, and in the parasitic nematodes Ascaris suum and Trichostrongylus
      colubriformis. DYRPLQFamide (1 nM-10 microM; n > or =6) produced contraction of
      innervated dorsal and ventral Ascaris body wall muscle preparations (10 microM,
      6.8+/-1.9 g; 1 microM, 4.6+/-1.8 g; 0.1 microM, 4.1+/-2.0 g; 10 nM, 3.8+/-2.0 g;
      n > or =6), and also caused a qualitatively similar, but quantitatively lower
      contractile response (10 microM, 4.0+/-1.5 g, n=6) on denervated muscle strips.
      Ovijector muscle displayed no measurable response (10 microM, n=5). nlp-12 cDNAs
      were characterised from A. suum (As-nlp-12) and T. colubriformis (Tc-nlp-12),
      both of which show sequence similarity to C. elegans nlp-12, in that they encode
      multiple copies of -LQFamide peptides. In C. elegans, reverse transcriptase (RT)
      PCR analysis showed that nlp-12 was transcribed throughout the life cycle,
      suggesting that DYRPLQFamide plays a constitutive role in the nervous system of
      this nematode. Transcription was also identified in both L3 and adult stages of
      T. colubriformis, in which Tc-nlp-12 is expressed in a single tail neurone.
      Conversely, As-nlp-12 is expressed in both head and tail tissue of adult female
      A. suum, suggesting species-specific differences in the transcription pattern of
      this gene.

PMID- 16600247
TI  - Anaplasma phagocytophilum-infected neutrophils enhance transmigration of Borrelia
      burgdorferi across the human blood brain barrier in vitro.
AB  - The manifestations of Lyme disease, caused by Ixodes spp. tick-transmitted
      Borrelia burgdorferi, range from skin infection to bloodstream invasion into the
      heart, joints and nervous system. The febrile infection human granulocytic
      anaplasmosis is caused by a neutrophilic rickettsia called Anaplasma
      phagocytophilum, also transmitted by Ixodes ticks. Previous studies suggest that
      co-infection with A. phagocytophilum contributes to increased spirochetal loads
      and severity of Lyme disease. However, a common link between these tick
      transmitted pathogens is dissemination into blood or tissues through blood
      vessels. Preliminary studies show that B. burgdorferi binds and passes through
      endothelial barriers in part mediated by host matrix metalloproteases. Since
      neutrophils infected by A. phagocytophilum are activated to release bioactive
      metalloproteases and chemokines, we examined the enhanced B. burgdorferi
      transmigration through vascular barriers with co-infection in vitro. To test
      whether endothelial transmigration is enhanced with co-infection, B. burgdorferi
      and A. phagocytophilum-infected neutrophils were co-incubated with EA.hy926 cells
      (HUVEC-derived) and human brain microvascular endothelial cells in Transwell
      cultures. Transmigration of B. burgdorferi through endothelial cell barriers was
      determined and endothelial barrier integrity was measured by transendothelial
      electrical resistivity. More B. burgdorferi crossed both human BMEC and EA.hy926
      cells in the presence of A. phagocytophilum-infected neutrophils than with
      uninfected neutrophils without affecting endothelial cell integrity. Such a
      mechanism may contribute to increased blood and tissue spirochete loads.

PMID- 16600248
TI  - Activation of Ca2+ -activated potassium channels is involved in
      lysophosphatidylcholine-induced monocyte adhesion to endothelial cells.
AB  - OBJECTIVE: Ca(2+)-activated K(+)-channels (BK(Ca)) play an important role in
      lysophosphatidylcholine (LPC)-induced endothelial dysfunction. Aim of our study
      was to investigate whether LPC-induced activation of BK(Ca) is also involved in
      monocyte adhesion to endothelial cells (EC). METHODS AND RESULTS: Measurement of
      membrane potential (MP) was performed using the fluorescence dye DiBAC. Adhesion
      of the monocytotic cell line U937 to EC was analysed by (3)[H]-thymidine-adhesion
      assay. Expression of ICAM-1 and VCAM-1 were analyzed by FACS. LPC induced a
      hyperpolarization of EC in a dose-dependent manner with the maximum seen with 2
      microM. This was prevented by the BK(Ca)-inhibitor iberiotoxin (IBX, 100nM).
      Adhesion of U937 cells to EC was increased after stimulation of EC with LPC. This
      effect was time-dependent with the maximum seen after 4h. LPC-induced adhesion
      was significantly reduced when EC were co-incubated with IBX, or NAD(P)H oxidase
      inhibitor diphenyleneiodonium (DPI, 5 microM) and also blocked by addition of 2
      aminoethoxydiphenylborate (2-APB, 100 microM) or the calcium-chelator BAPTA (10
      microM). Stimulation of U937 cells with LPC did not result in an increased
      adhesion to unstimulated EC. CONCLUSION: Activation of the endothelial BK(Ca)
      plays an important role in monocyte adhesion to endothelial cells.

PMID- 16600249
TI  - Superoxide dismutase and catalase inhibit oxidized low-density lipoprotein
      induced human aortic smooth muscle cell proliferation: role of cell-cycle
      regulation, mitogen-activated protein kinases, and transcription factors.
AB  - Several antioxidant enzymes, including copper, zinc-superoxide dismutase (Cu, Zn
      SOD) and catalase, have been suggested to be protective against the proliferation
      of vascular smooth muscle cells exposed to oxidative stress. In the present
      study, we investigated effects of Cu, Zn-SOD and/or catalase on oxLDL-induced
      proliferation of, and intracellular signaling in, human aortic smooth muscle
      cells (HASMCs). HASMCs were transfected with adenovirus carrying the human Cu, Zn
      SOD gene and/or the human catalase gene. This resulted in a high level of Cu, Zn
      SOD and/or catalase overexpression and decreased oxLDL-induced proliferation. Cu,
      Zn-SOD and/or catalase also arrested cell cycle progression, which was associated
      with decreased expression of cyclin D1, cyclin E, CDK2, and CDK4 and upregulation
      of p21(Cip1) and p27(Kip1). Phosphorylation studies on ERK1/2, JNK, and p38,
      three major subgroups of mitogen activator protein kinases, demonstrated that Cu,
      Zn-SOD and/or catalase overexpression suppressed ERK1/2 and JNK phosphorylation.
      Gel-mobility shift analysis showed that oxLDL caused an increase in the DNA
      binding activity of activator protein-1 (AP-1) and nuclear factor kappaB (NF
      kappaB), which was inhibited by Cu, Zn-SOD and/or catalase overexpression. These
      results provide the first evidence that overexpression of Cu, Zn-SOD and/or
      catalase in HASMCs attenuates the cell proliferation caused by oxLDL stimulation
      and that this inhibitory effect is mediated via downregulation of ERK1/2 and JNK
      phosphorylation and AP-1 and NF-kappaB inactivation. These observations support
      the feasibility of the increase of Cu, Zn-SOD and/or catalase expression in human
      smooth muscle cells as a means of protection against oxidant injury.

PMID- 16600250
TI  - Fenofibrate induces plaque regression in hypercholesterolemic atherosclerotic
      rabbits: in vivo demonstration by high-resolution MRI.
AB  - INTRODUCTION: Fenofibrate has shown to reduce major cardiovascular events and
      slow angiographic progression of coronary atherosclerosis. The postulated
      mechanism of action is via the activation of peroxisomal proliferator-activated
      receptor-alpha (PPAR-alpha), a nuclear transcription factor that controls a
      variety of cellular functions. We investigated the anti-atherogenic effects of
      fenofibrate on previously established experimental atherosclerotic lesions.
      METHOD: Atherosclerotic lesions were induced in the abdominal aorta of New
      Zealand white (NZW) rabbits (n=19) by a combination of a double-balloon injury
      and a 9-month hypercholesterolemic diet. The rabbits were randomized into placebo
      or fenofibrate group. The corresponding treatments were added to the
      hypercholesterolemic diet. All rabbits underwent MRI examination at randomization
      and after 6 months of treatment, and were then sacrificed for histopathology.
      RESULTS: LDL-cholesterol was similarly elevated at randomization and follow-up,
      and was not significantly modified by fenofibrate therapy. HDL-cholesterol
      decreased (-27+/-10%, p=0.04) in the placebo and increased (+36.8+/-2%, p=0.04)
      in the fenofibrate group. MRI showed comparable vessel wall area (VWA) at
      randomization in both groups. At 15months, a significant increase in VWA was seen
      in the placebo group (15+/-4%, p=0.007), while fenofibrate treatment was
      associated with a regression (-11+/-4%, p=0.041) of previously established
      lesions. Fenofibrate also decreased macrophage and increased smooth muscle
      cell/collagen content of atherosclerotic lesions. CONCLUSION: MRI measurements
      can, in conjunction with in vitro histological measurements, contribute to the
      understanding of the actions of pharmacologic agents in experimental models of
      atherosclerosis. Fenofibrate significantly regresses atherosclerotic lesions and
      induced changes in plaque composition associated with a more "stable" phenotype
      (reduced macrophages and increased SMC). These observations support the potential
      anti-atherogenic effects of PPAR-alpha agonists.

PMID- 16600251
TI  - Treating intermittent claudication with Tibetan medicine Padma 28: does it work?
AB  - Herbal drugs are being increasingly used in medical practice, often without
      appropriate scrutiny of their safety and efficacy. The medicinal product Padma 28
      is a fixed combination with Tibetan origin, used in Europe since the 1960s for
      the symptomatic treatment of circulatory disorders, including those of peripheral
      arterial occlusive disease (PAOD). We have conducted an analysis of all available
      data on this herbal drug from published literature as well as from original data
      we obtained from contacting the authors of published papers, reports and the
      manufacturer. A total of 19 trials have reported on 2084 patients to date, 444 of
      whom were in six controlled clinical studies on PAOD. A meta-analysis of five
      trials showed Padma 28 to increase walking distance by >100m in 18.2% of the
      patients with verum, versus 2.1% with placebo (P<0.001; odds ratio: 10 [95% CI
      3.03, 33.33]; RR: 0.12; number needed to treat=6.2). The safety profile appears
      to be favourable. Available evidence shows that Padma 28 provides significant
      relief from PAOD-related symptoms (i.e. walking distance), probably of the same
      order of magnitude as other employed medications. However, larger confirmatory
      RCTs are desirable.

PMID- 16600252
TI  - The role of repair tension on tendon to bone healing in an animal model of
      chronic rotator cuff tears.
AB  - Rotator cuff tendon tears are one of the most common shoulder injuries. Although
      surgical repair is typically beneficial, re-tearing of the tendons frequently
      occurs. It is generally accepted that healing is worse for chronic tears than
      acute tears, but the reasons for this are unknown. One potential cause may be the
      large tensions that are sometimes required to repair chronically torn tendons
      back to bone (i.e., repair tension). Therefore, the objective of this study was
      to utilize an animal model of chronic rotator cuff repairs to investigate the
      role of increased repair tension on tendon to bone healing. We hypothesized that
      an increase in repair tension would be related to detrimental changes to the
      healing insertion site. To test this hypothesis, the supraspinatus tendon of rats
      was surgically detached and then repaired immediately or after a delay of 2, 4,
      or 16 weeks. The repair tension was measured using a tensiometer and the
      mechanical properties, collagen organization, and protein expression of the
      healing insertion site were evaluated 4 and/or 16 weeks following repair. We
      found that the repair tension increased with time following detachment, and was
      related to a decrease in the failure properties and viscoelastic peak stress and
      an increase in cross-sectional area and stiffness of the insertion site.
      Therefore, repair tension should be minimized in the clinical setting. Future
      studies will include additional animal model studies involving the relationship
      between tension and muscle properties and a clinical study investigating the role
      of repair tension on repair failure.

PMID- 16600253
TI  - Speciation of alkylated dibenzothiophenes through correlation of structure and
      gas chromatographic retention indexes.
AB  - The gas chromatographic (GC) speciation of polycyclic aromatic sulfur
      heterocycles (PASH) in deeply desulfurized fuels is difficult without recourse to
      authentic standard compounds. Here we investigate the GC retention indexes for 30
      alkylated dibenzothiophenes on two methylphenylsiloxane stationary phases of
      different selectivity (5% and 50% phenyl groups) with a view to avoid the
      synthesis of all congeners. The influence of the substitution pattern on the
      retention indexes is discussed. With the measured data it is possible to carry
      out a multiple linear regression (MLR) to calculate parameters for predicting the
      retention indexes of unknown polymethylated isomers based only on their
      structural features. Nine trimethyldibenzothiophene in a synthesis product are
      identified through their retention indexes. The retention indexes for a total of
      43 alkyldibenzothiophenes are listed.

PMID- 16600254
TI  - Apolar chromatography on Sephadex LH-20 combined with high-speed counter-current
      chromatography. High yield strategy for structurally closely related analytes
      Destruxin derivatives from Metarhizium anisopliae as a case study.
AB  - A novel high yield isolation procedure for lipophilic cyclic peptide derivatives
      is presented. Destruxin (dtx) A, B, D, E, and E-diol retrieval from Metarhizium
      anisopliae culture broth was achieved with a three-step purification protocol.
      After liquid-liquid extraction column chromatography over Sephadex LH-20 served
      as enrichment step. High-speed counter-current chromatography (HSCCC) was used
      for the final purification. Within the first chromatographic step dtx D and dtx E
      diol were separated in purities exceeding 90%. The separation of dtx A, B, and E
      was achieved from an enriched Sephadex LH-20 fraction by a HSCCC protocol using
      light petroleum-ethyl acetate-methanol-water = 2:5:2:5 (v/v) as eluent system.
      These derivatives were obtained in purities above 98% and total yields exceeding
      40%.

PMID- 16600255
TI  - Sample preparation on polymeric solid phase extraction sorbents for liquid
      chromatographic-tandem mass spectrometric analysis of human whole blood--a study
      on a number of beta-agonists and beta-antagonists.
AB  - Alternative strategies for sample preparation of human blood samples were
      evaluated including protein precipitation (PP) and solid phase extraction (SPE)
      on Waters Oasis polymeric columns. Gradient chromatography within 15 min was
      performed on a Hypersil Polar-RP column combined with a Sciex API 2000 triple
      quadrupol instrument equipped with an electro-spray interface. Beta-agonists and
      beta-antagonists available on the Swedish market were included in the study. A
      combination of zinc sulphate and ethanol was found effective for PP. A clear
      supernatant was achieved that either could be injected directly on the LC-MS-MS
      system for analysis or transferred to a SPE column for further extraction and
      analyte concentration. Retention on the hydrophilic-lipophilic balanced sorbent
      HLB as well as the mixed mode cationic MCX and anionic MAX sorbents were
      investigated. On HBL the relative lipophilicity of the target analytes was
      investigated. At a high pH when the amino alcohols are deprotonised the more non
      polar analytes (e.g., carvediol, betaxolol, bisoprolol and propranolol) were well
      retained on the sorbent and for the majority methanol content higher than 50% in
      water (v/v) was needed for elution. Some analytes though, with additional weak
      acidic functionalities (fenoterol, salbutamol, sotalol, and terbutaline) were
      poorly retained. On MAX the retention of these weak acids was improved when
      loaded under basic conditions but under neutral conditions analyte recoveries was
      comparable with HLB. On MCX all the analytes were well retained allowing a wash
      step of 100% methanol at neutral and low pH. By applying the supernatant from PP
      in combination with an additional portion of aqueous formic acid (2%) the
      analytes could be loaded and retained. High extraction recoveries were found for
      most analytes but for a few, significant losses were seen during PP (e.g.,
      formoterol) and/or evaporation (e.g., fenoterol, formoterol, labetalol and
      terbutaline). The effectiveness of the sample preparation was evaluated by ESI
      ion-suppression studies by post column infusion of the target analyte. An ethanol
      zinc sulphate aq mixture was found to be more effective than acetonitrile,
      methanol or ethanol for PP of human whole blood samples. Beside suppression by
      salts in the front peak, only limited suppression from other artefacts such as
      more lipophilic compounds was found late in the chromatograms. Some tendency
      though to concentrate more lipophilic artefacts on the Oasis sorbents was seen.
      These findings show that the Oasis MCX sorbent is well suited for sample
      preparation of beta-agonists and beta-antagonists from human whole blood if the
      objective is to cover a great number of the analytes in the same assay.

PMID- 16600256
TI  - A numerical scheme to diagnose interferences in gas chromatography-mass
      spectrometry quantitation of coeluting isotopically labeled and unlabeled
      counterparts with partially overlapping ion profiles.
AB  - Quantitation of chromatographically coeluting compounds with partially
      overlapping mass profiles is a challenging task, especially if only a low
      resolution mass spectrometer is available. To examine whether theoretical
      predictions can be utilized to determine the appropriate concentration ranges of
      the coeluting compounds that satisfy the non-interfering condition, we utilized
      an algorithm based upon a two-component model to compare the experimentally
      measured and predicted quantitation errors. Selected unlabeled and 13C-labeled
      polychlorinated biphenyl (PCB) congeners were investigated as model compounds.
      Standard solutions containing various concentration ratios of the unlabeled and
      13C-labeled PCB congeners were analyzed, and the data were used to compare with
      theoretical predictions derived from the chlorine isotopic distributions (35Cl
      and 37Cl). Good agreements between experimental predictions and theoretical
      predictions were found on the magnitude of interferences for quantitation of 13C
      labeled PCB congeners, as well as on the variability of the quantitation errors
      with the concentration ratio of 13C-labeled and unlabeled PCB counterparts. In
      addition, the magnitude of interferences considered in the present study was
      highly dependent upon the number of coexisting ions included for quantitation and
      their relative abundances in the mass spectrum. All these results suggest that
      the magnitude of interferences in quantifying a pair of coeluting compounds with
      partially overlapping mass spectral profiles can be effectively determined and
      minimized by carefully selecting the concentration ratio of the coeluting
      compounds and/or the number of quantitation ions. Finally, the selection of the
      experimental parameters to satisfy the non-interfering condition can be made
      purely on the basis of theoretical considerations.

PMID- 16600257
TI  - Ion chromatography-atmospheric pressure chemical ionization mass spectrometry for
      the determination of trace chlorophenols in clam tissues.
AB  - A novel analytical method has been developed for the determination of 14 trace
      chlorophenols in clam tissues by ion chromatography (IC) coupled with atmospheric
      pressure chemical ionization mass spectrometry (APCI-MS) in the negative mode.
      The method comprised a fast ultrasound-assisted extraction using a mixture of
      methanol/water (4:1v/v) containing 5% triethylamine (TEA) as extraction solvent,
      solid-phase extraction with an Oasis HLB cartridge and gradient separation using
      KOH/acetonitrile at a flow rate of 1.0 mL/min on an IonPac AG11 guard column (50
      mm x 4.0 mm I.D.) and an IonPac AS11 analytical column (250 mm x 4.0 mm I.D.).
      The molecular ions m/z [M-H](-) 127, 129; 161, 163; 195, 197 and 263, 265, 267
      were selected for quantification in the selected ion monitoring (SIM) mode for
      monochlorophenols (MCPs), dichlorophenols (DCPs), trichlorophenols (TCPs) and
      pentachlorophenol (PCP), respectively. The average recoveries of the objective
      compounds spiked in clam tissues were between 80.2% and 98.2%. Within-day and day
      to-day relative standard deviations were less than 12.6% and 13.2%, respectively.
      The optimum IC-APCI-MS conditions were successfully applied to the analyses of 14
      trace chlorophenols in clam tissues.

PMID- 16600258
TI  - Chiral separation of acidic drug components by open tubular electrochromatography
      using avidin immobilized capillaries.
AB  - Avidin was immobilized covalently onto the inner surface of fused silica
      capillaries as a stationary phase in an open tubular capillary
      electrochromatography (OT-CEC) for chiral separations. The modification was
      attained by a combination of glutaraldehyde with both an amino-silylated fused
      silica surface and avidin using a Schiff base formation reaction. This method
      couples the advantage of high efficiency and small consumption of a chiral
      selector with the possibility of UV detection without limitations of protein
      absorption. In addition, the prepared capillary was stable for 50 days with over
      100 runs. To evaluate the electrochromatographic performance of the prepared
      capillaries, the chiral separation of abscisic acid and arylpropionic acids were
      investigated. Effects of the modification condition of protein, pH of running
      buffer, and an organic modifier on the enantioseparation were also investigated.
      In addition, the avidin immobilized capillary was employed for the selective
      chiral analysis with an electrospray ionization mass spectrometry (ESI-MS)
      detection scheme.

PMID- 16600259
TI  - Analysis of green tea extract dietary supplements by micellar electrokinetic
      chromatography.
AB  - Dietary supplements are growing in popularity as a source of catechins such as
      epigallocatechin gallate (EGCG). The first determination of five catechins in
      green tea extract dietary supplements using an extraction followed by micellar
      electrokinetic chromatography (MEKC) with UV detection is presented here. The
      optimum run buffer is 5 mM borate-60 mM phosphate with 50 mM SDS at pH 7.00 with
      detection at 210 nm. The limit of detection is 2-3 microg/mL (S/N=3) and the
      limit of quantitation is 6-8 microg/mL (S/N = 10). Results indicate that the
      amount of catechins varies greatly among manufacturers, between capsules of the
      same manufacturers, and between batches.

PMID- 16600260
TI  - Optimisation of a solid-phase microextraction method for the determination of
      parabens in water samples at the low ng per litre level.
AB  - A procedure for the determination of five esters of p-hydroxybenzoic acid
      (parabens) in water samples is presented. Analytes (methyl, ethyl, propyl, butyl
      and benzyl paraben) are concentrated on a solid-phase microextraction (SPME)
      fibre, converted on their tert-butyldimethylsilyl derivatives and selectively
      determined using gas chromatography in combination with tandem mass spectrometry
      (GC-MS/MS). Influence of different factors on the efficiency of extraction and on
      fibre derivatization steps is described in detail. For all species, the highest
      enrichment factors were achieved using a polyacrylate (PA) fibre exposed directly
      to stirred water samples, containing 150 mg/ml of sodium chloride, at room
      temperature. Performance of the further on-fibre derivatization reaction was also
      maximum at room temperature, considering a short exposition period of the SPME
      fibre to vapours of the silylation reagent. Under optimised conditions, the
      proposed method achieved quantification limits from 0.001 to 0.025 ng/ml and it
      was free of matrix effects; therefore, external calibration can be used as the
      quantification technique. From our knowledge, this work describes the first
      application of SPME and gas chromatography to the determination of parabens in
      water. The analysis of a limited number of real samples revealed the presence of
      parabens in raw sewage water at concentrations up to 3 ng/ml.

PMID- 16600261
TI  - Poly(methyloctylsiloxane) immobilized on silica as a sorbent for solid-phase
      extraction of some pesticides.
AB  - A laboratory-made sorbent for solid-phase extraction (SPE) was obtained by
      thermal immobilization of poly(methyloctylsiloxane) (PMOS) onto silica.
      Cartridges packed with the new sorbent were used for the simultaneous
      determination of imazethapyr, nicosulfuron, diuron, linuron and chlorimuron-ethyl
      in water. These pesticides were separated and quantified using high-performance
      liquid chromatography with diode array detection (HPLC-DAD). The recoveries
      achieved with the laboratory-made PMOS cartridges were compared with those of
      some commercially available silica-based and polymer-based cartridges having C18,
      C8 and NH(2) pendant groups. Method validation using the laboratory-made sorbent
      was performed for the five pesticides at three fortifications levels (1x, 2x and
      10x the limit of quantification of each pesticide). The laboratory-made PMOS
      cartridge has low cost preparation and showed good recoveries (72-111%) for all
      pesticides. Repeatability and intermediate precision were lower than 15%. Its
      performance was similar or even better, in some cases, than those of the
      commercial cartridges.

PMID- 16600262
TI  - Development of a solid-phase microextraction method for the analysis of phenolic
      flame retardants in water samples.
AB  - A solid-phase microextraction (SPME) method for the ultra-trace determination of
      brominated phenols in aqueous samples has been developed and is reported for the
      first time to the best of our knowledge. 3,5,3',5'-tetrabromobisphenol A (TBBPA),
      the most widely used brominated flame retardant, and other phenolic flame
      retardants in commercial use, such as 2,4-dibromophenol (2,4-DBP), 2,4,6
      tribromophenol (TBP) and pentabromophenol (PBP) have been included as target
      analytes. The analytical procedure involves the in situ acetylation-SPME and gas
      chromatography-mass spectrometry (GC-MS) determination of the target analytes. A
      multi-factor categorical experimental design was created to study the main
      parameters affecting the extraction efficiency, allowing also the evaluation of
      interaction effects between factors. The factors studied were type of fiber,
      extraction mode, exposing the fiber directly into the sample (DSPME) or into the
      headspace over the sample (HSSPME), and extraction temperature. Carboxen
      polydimethylsiloxane (CAR-PDMS) fiber appeared to be the most suitable of the
      five fibers tested for the extraction of most compounds, excluding PBP and TBBPA
      for which polydimethylsiloxane (PDMS) was the most efficient coating. The highest
      response was achieved for both fibers sampling in headspace mode at 100 degrees
      C. In order to test the linearity of the method, calibration studies were
      performed with both CAR-PDMS and PDMS coatings. For both fibers, the method was
      linear in a range of 2 orders of magnitude, giving relative standard deviation
      (RSD%) below 10% for most compounds and detection limits at the low pg/mL level.
      In addition, the feasibility of the method for simultaneous determination of
      chlorinated and brominated phenols was studied. Finally, the method was applied
      to several real samples including tap water and effluent and influent waste water
      samples from an urban treatment plant, in which several phenolic compounds, such
      as phenol, methylphenols and chlorophenols, could be detected and quantified.

PMID- 16600263
TI  - Neutral additives enhance the metal-chelate affinity adsorption of nucleic acids:
      role of water activity.
AB  - Immobilized metal-chelate affinity chromatography has been widely used in the
      purification of proteins, and we have recently found that it can also be applied
      to purification of nucleic acids through interactions involving exposed bases,
      especially purines. Here we report that the inclusion of moderate quantities of
      neutral solutes in the buffer substantially enhances the binding affinity of
      nucleic acids for immobilized metal-chelate affinity adsorbents. Addition of 20%
      (v/v) of solutes such as ethanol, methanol, isopropanol, n-propanol, and dimethyl
      sulfoxide enhances the initial affinity of binding of total yeast RNA by 4.4-,
      3.8-, 3.7-, 3.0-, and 2.8-fold, respectively for Cu(II)-iminodiacetic acid (IDA)
      agarose adsorbent, and the weaker adsorption by Cu(II)-nitrilotriacetic acid
      (NTA) agarose was even more strongly enhanced. The adsorption affinities of the
      smaller oligodeoxynucleotide molecules A20, G20, C20 and T20 also increase with
      the addition of ethanol, suggesting that the effect is not significantly mediated
      by conformational changes. Binding enhancement generally correlates with
      reduction of water activity by the various solutes, as predicted by several
      models of solution thermodynamics, consistent with an entropic contribution by
      displacement of waters from the metal-chelate. Interestingly, the enhancement was
      not seen with the proteins bovine serum albumin and lysozyme.

PMID- 16600264
TI  - Different sample stacking strategies to analyse some nonsteroidal anti
      inflammatory drugs by micellar electrokinetic capillary chromatography in mineral
      waters.
AB  - Three on-column preconcentration techniques were compared to analyse a group of
      nonsteroidal anti-inflammatory drugs (NSAIDs) using micellar electrokinetic
      capillary chromatography (MEKC) under pH-suppressed electroosmotic flow (EOF) in
      water samples. The analysed drugs were ibuprofen, fenoprofen, naproxen,
      ketoprofen, and diclofenac sodium. The micellar background electrolyte (BGE)
      solution was formed by 75 mM sodium dodecyl sulfate (SDS), 40% (v/v)
      acetonitrile, and 25 mM sodium phosphate at pH 2.5. When this BGE solution was
      used the applied voltage was reversed, -10 kV, and the drugs were separated
      within 20 min. The on-column preconcentration modes, characterised all of them
      for the sample matrix removal out of the capillary by itself under a reverse
      potential at the same time as the EOF was reduced, were stacking with reverse
      migrating micelles (SRMM), stacking with reverse migrating micelles-anion
      selective exhaustive injection (SRMM-ASEI), and field-enhanced sample injection
      with reverse migrating micelles (FESI-RMM). The sensitivity was improved up to
      154-, 263-, and 63-fold, respectively when it was calculated through the peaks
      height. The optimised methods were validated with spiked mineral water by
      combining off-line solid-phase extraction (SPE) and the proposed on-line sample
      stacking strategies. The detection limits (LODs) of NSAIDs in mineral water were
      at ng/L levels.

PMID- 16600265
TI  - Analysis of etimicin sulfate by liquid chromatography with pulsed amperometric
      detection.
AB  - A new method for determination of etimicin's (ETM) purity and content is
      developed by liquid chromatography (LC) and pulsed amperometric detection (PAD).
      A reversed-phase ion-pair LC method with pulsed amperometric detection on a gold
      electrode after post-added NaOH is described. The mobile phase consisted of an
      aqueous solution containing 0.033 mol L(-1) oxalic acid, 0.012 mol L(-1)
      heptafluorobutyric acid, and 210 mL L(-1) acetonitrile with pH 3.40 adjusting by
      dilute NaOH solution. The total analysis time was not more than 30 min. The
      effects of the different chromatographic parameters on the separation were also
      investigated. A number of commercial samples of etimicin sulfate were analyzed
      using this method.

PMID- 16600266
TI  - Application of the chromatographic retention index system for the estimation of
      the calibration constants of permeation passive samplers with
      polydimethylsiloxane membranes.
AB  - The paper presents the results of research on the calibration of permeation
      passive samplers equipped with polydimethylsiloxane (PDMS) membranes using the
      physico-chemical properties of the analytes. Strong correlations were found
      between the calibration constants of the samplers and the linear temperature
      programmed retention indices of the analytes determined on columns coated with
      pure PDMS (r2 = 0.914). These correlations make it possible to estimate the
      calibration constants for unidentified analytes, which is impossible when using
      conventional procedures. This, in turn, enables the deployment of permeation
      passive samplers in the same way in which active samplers are deployed. The
      reproducibility of the calibration constants determined in different laboratories
      and retention indices determined using different chromatographic systems was very
      good, indicating that the calibration constants estimated using this approach
      should be reproducible as well. The approach proposed should lead to more
      widespread use of permeation passive samplers.

PMID- 16600267
TI  - Direct and sensitive analysis of methamphetamine, ketamine, morphine and codeine
      in human urine by cation-selective exhaustive injection and sweeping micellar
      electrokinetic chromatography.
AB  - Cation-selective exhaustive injection and sweeping micellar electrokinetic
      chromatography (CSEI-Sweep-MEKC) was directly used to test some abuse drugs in
      human urine, including morphine (M), codeine (C), ketamine (K) and
      methamphetamine (MA). First, phosphate buffer (50 mM, pH 2.5) containing 30%
      methanol was filled into uncoated fused silica capillary (40 cm, 50 microm I.D.),
      then high conductivity buffer (100 mM phosphate, 6.9 kPa for 99.9 s) was
      followed. Electrokinetic injection (10 kV, 500 s) was used to load samples and to
      enhance sensitivity. The stacking step and separation were performed at -20 kV
      and 200 nm using phosphate buffer (25 mM, pH 2.5) containing 20% methanol and 100
      mM sodium dodecyl sulfate. Using CSEI-Sweep-MEKC, the analytes could be
      simultaneously analyzed and have a detection limit down to ppb level. It was
      unnecessary to have sample pretreatments. During method validation, calibration
      plots were linear (r>or=0.9982) over a range of 150-3,000 ng/mL for M and C, 250
      5,000 n g/mL for MA, and 50-1,000 ng/mL for K. The limits of detection were 15
      ng/mL for M and C, and 5 ng/mL for MA and K (S/N=3, sampling 500 s at 10 kV).
      Comparing with capillary zone electrophoresis, the results indicated that this
      stacking method could increase 6,000-fold sensitivity for analysis of MA. Our
      method was applied for analysis of 28 real urine samples. The results showed good
      coincidence with immunoassay and GC-MS. This method was feasible for application
      to detect trace levels of abused drugs in forensic analysis.

PMID- 16600268
TI  - Monolithic poly(p-methylstyrene-co-1,2-bis(p-vinylphenyl)ethane) capillary
      columns as novel styrene stationary phases for biopolymer separation.
AB  - Novel monolithic capillary supports (200 microm I.D.) were prepared by
      polymerisation of methylstyrene (MS) and 1,2-bis(p-vinylphenyl)ethane (BVPE) as a
      crosslinker in the presence of inert diluents (porogens). These polymeric
      reversed-phases (MS/BVPE) showed excellent mechanical stability and minimised
      swelling in organic solvents. The chromatographic potential of monolithic MS/BVPE
      as a stationary phase for micro-high-performance liquid chromatography (mu-HPLC)
      was investigated by the separation of proteins and peptides applying reversed
      phase (RP) and nucleic acids applying ion-pair reversed-phase (IP-RP) conditions.
      The permeability and chromatographic efficiency of the capillary columns were
      found to be highly influenced by the total monomer to porogen content as well as
      by the microporogen nature and its ratio. In the course of these optimisation
      studies, monoliths covering a broad permeability range were fabricated. The
      application of volumetric flow rates up to 200 microl/min allowed swift
      resolution of proteins, while smaller biomolecules were successfully separated at
      a higher overall porosity. A protein test mixture containing ribonuclease A,
      cytochrome c, alpha-lactalbumin, beta-lactoglobulin B and ovalbumin was thus
      baseline separated in 35s, a homologous series of phosphorylated oligothymidylic
      acids [d(pT)12-18] in less than 2 min.

PMID- 16600269
TI  - Mass spectrometric analysis of enzymatic digestion of denatured collagen for
      identification of collagen type.
AB  - Collagen type II and I from bovine were thermally denatured and digested with
      trypsin. The digest mixture was analyzed with liquid chromatography/electrospray
      ionization mass spectrometry (LC/ESI-MS). Peptides in the digest mixture were
      identified by mass spectrometry/mass spectrometry (MS/MS) sequencing. The results
      indicated that the digest mixtures of collagen type II and I contained lots of
      specific peptides and common peptides. Specific peptides could be used as index
      for identifying collagen type. Articular cartilage from bovine was pretreated and
      analyzed with the same method to determine the collagen types. The result
      indicated that the method developed was effective for identification of collagen
      types. The research provided a possible approach for collagen identification in
      particular tissues.

PMID- 16600270
TI  - Determination of cyanide in microliter samples by capillary electrophoresis and
      in-capillary enzymatic reaction with rhodanese.
AB  - This paper describes a method for the determination of cyanide using in-capillary
      enzymatic reaction with rhodanese. Poorly absorbing cyanide is in rhodanese
      reaction transformed into highly absorbing thiocyanate that is further separated
      by capillary electrophoresis (CE) and determined spectrophotometrically at 200
      nm. Cyanide is thus estimated indirectly from the result of thiocyanate
      quantification and moreover, it can be easily determined with sufficient
      sensitivity by means of CE apparatus equipped with common UV detector. The linear
      detection range for concentration versus peak area for the assay is from 15 to
      500 microM (correlation coefficient 0.997) with a detection limit of 3 microM and
      a limit of quantitation 9 microM. The inter-day reproducibility of the peak area
      was below 3.2% and the inter-day reproducibility of the migration time below
      0.1%. The method is relatively rapid, simple and can be easily automated.
      Moreover, only limited amount of the sample is required.

PMID- 16600271
TI  - Determination of orthophthalaldehyde in air using 2,4-dinitrophenylhydrazine
      impregnated silica cartridge and high-performance liquid chromatography.
AB  - A new method is described for the determination of orthophthalaldehyde in air
      which is used for the disinfection of various instruments (e.g. endoscopes) in
      hospital. Orthophthalaldehyde in air was collected with a silica gel cartridge
      impregnated with acidified 2,4-dinitrophenylhydrazine (DNPH-cartridge) and
      derivatives were analyzed by high-performance liquid chromatography (HPLC). In
      this study, the derivatization was examined by comparing the process with three
      phthalaldehyde isomers (ortho-, iso- and tere-). In the case of iso- and tere
      phthalaldehyde, derivatives synthesized with excess of aldehyde consisted mainly
      of mono-derivatives, and derivatives synthesized with excess of DNPH consisted
      mainly of bis-derivative. In the case of orthophthalaldehyde, derivative
      consisted of only bis-derivative and mono-derivative was never observed under any
      conditions. Orthophthalaldehyde was completely retained by the DNPH-cartridge
      during air sampling, however, the derivatization reaction was incomplete and
      unreacted orthophthalaldehyde was flushed from the cartridge during the
      subsequent solvent extraction process. Unreacted orthophthalaldehyde and DNPH
      reacted again in the extraction solvent solution. Immediately after the solvent
      extraction, both mono- and bis-DNPhydrazone derivatives of orthophthalaldehyde
      were present in the solution. However, over time, the mono-derivative decreased
      and bis-derivative increased until only the bis-derivative was left allowing
      accurate determination of the orthophthalaldehyde concentration. The
      transformation of mono-derivative to bis-derivative was faster in polar aprotic
      solvents such as acetonitrile, dimethyl sulfoxide and ethyl acetate.
      Transformation was found to occur most quickly in acetonitrile solvent and was
      completed in 4 h in this case. It was possible to measure orthophthalaldehyde in
      air as bis-derivative using a DNPH impregnated silica cartridge and HPLC
      analysis.

PMID- 16600272
TI  - Experimental verification of sample-solvent induced modifier-solute peak
      interactions in biochromatography.
AB  - In a previous theoretical analysis based on equilibrium theory it has been shown
      how differences in the sample and elution modifier concentrations can lead to
      unexpected behavior of the solute eluted peaks such as retention time distortion,
      peak deformation and peak doubling. All these features are verified
      experimentally in this work using the polypeptide calcitonin and a variant of a
      specific monoclonal antibody as chromatographic model systems. For both
      experimental systems, the retention time distortion can be predicted with high
      accuracy by the solution of the equilibrium theory model. For the polypeptide,
      the predictions from the theory about the occurrence of peak deformation and
      double peaks has been successfully verified by a series of tailored experiments
      with positive as well as negative modifier perturbations.

PMID- 16600273
TI  - Electrochemically enhanced adsorption of phenol on activated carbon fibers in
      basic aqueous solution.
AB  - Electrosorption isotherms and thermodynamics of phenol on activated carbon fibers
      (ACFs) in basic solution, as well as the factors (bias potential, initial
      concentration, and electrolyte) affecting adsorption/electrosorption kinetics,
      were investigated. The kinetics, which followed the Lagergren adsorption rate
      law, exhibited a variety of responses depending on bias potential, initial
      concentration, and electrolyte. The electrosorption isotherms were in agreement
      with the classical models of Langmuir and Freundlich, but the former gave more
      satisfactory correlation coefficients. With electrosorption at a bias potential
      of 700 mV from the basic solution, a nearly 10-fold enhancement of maximum
      adsorption capacity was achievable. The electrosorption free energy
      (DeltaG(ads)), enthalpy (DeltaH(ads)), and entropy (DeltaS(ads)) of phenol on the
      ACFs were calculated from adsorption isotherms at different temperatures. The
      results indicated that electrosorption of phenol in basic solution was
      spontaneous and exothermic. Furthermore, it was assessed that electrosorption
      occurred by dipole-dipole interaction with DeltaH(ads) of -20.14 kJ mol(-1)
      besides suppositional electrostatic interaction.

PMID- 16600274
TI  - Mesoporous silica-titania composed materials.
AB  - Titania mesosized particles were obtained by TiCl4 hydrolysis in Aerosol
      OT/water/n-hexane microemulsion. These particles were incorporated in surfactant
      templated silica mesoporous materials of MCM-41 and MCM-50 structures. Results
      depended on the surfactant: hexadecyltrimethylammonium bromide templated
      materials retained the honeycomb structure with small modifications in their
      characteristics. The dodecyltrimethylammonium bromide templated material changed
      from honeycomb to lamellar structure when the titania particles were included,
      with dramatic changes in the structure characteristics. The
      didodecyldimethylammonium bromide templated lamellar structure was retained after
      TIO2 inclusion, with a slight increase in the specific area, pore diameter and
      pore walls thickness.

PMID- 16600275
TI  - Line of charges in electrolyte solution near a half-space II. Electric field of a
      single charge.
AB  - The electric potential of a single charge in electrolyte solution near a
      dielectric or a semiconducting half-space is determined in closed form when the
      electrostatics is described by the linear Debye-Huckel (D-H) equation. The
      electric potential strongly depends on the Debye length of the solution, the
      substrate-to-solution dielectric constant ratio, and the Debye length of the
      semiconductor. The technique of Hankel transforms is shown to be a useful tool in
      solving such axially symmetric boundary value problems for the D-H equation.

PMID- 16600276
TI  - Photooxidation of dibenzothiophene on TiO(2)/hectorite thin films layered
      catalyst.
AB  - A new titanium(IV) oxide-hectorite nanofilm photocatalyst was prepared on quartz
      slides. It was evaluated in the photooxidation of dibenzothiophene (DBT) in
      nonpolar organic solution (tetradecane), as a model for diesel fuel. A removal
      regimen was developed consisting of catalytic photooxidation followed by
      adsorption of products on silica gel. Photooxidation of DBT was performed with
      and without catalyst, at 254 and 300 nm. Comparison was made with a commercially
      available TiO(2) catalyst, Degussa P25. The catalyst was analyzed by nitrogen
      adsorption, XRD, SEM, and TGA-DTA. DBT concentrations were measured by HPLC and
      UV spectrophotometry. Preliminary qualititative analysis of products was
      performed by UV and HPLC. Results indicated that the outlined process was
      effective in reducing sulfur levels to below 10 ppm sulfur.

PMID- 16600277
TI  - Suppression of electron-transfer characteristics of ferrocene by OTS monolayer on
      a silicon/electrolyte interface.
AB  - The passivating behavior of self-assembled monolayers (SAMs) of
      octadecyltrichlorosilane (OTS) on an n-type Si(100) electrode with and without a
      redox species like ferrocene in a polar non-aqueous medium has been investigated
      using techniques like contact angle measurements, Fourier transform infrared
      (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS) to understand the
      role of the monolayer. The electron-transfer behavior of ferrocene is found to be
      drastically affected by the presence of monolayer and the reasons for these are
      analyzed as a function of the change in resistance, dielectric thickness and
      coverage of the monolayer. Electrochemical impedance analysis in the presence of
      ferrocene gives the monolayer coverage as 0.998 and the apparent rate constant
      calculated from this gives 4.85 x 10(-12) cm s(-1) in comparison with 4.4 x 10(
      8) cm s(-1) for a similar electrode without any monolayer. A positive shift of
      200 mV in the flat-band potential after monolayer formation also suggests the
      covalent coupling of the silane monolayer offering a protective barrier.

PMID- 16600278
TI  - Biosorption of Cd(II), Cr(III), and Cr(VI) by saltbush (Atriplex canescens)
      biomass: thermodynamic and isotherm studies.
AB  - The biosorption data of Cd(II), Cr(III), and Cr(VI) by saltbush leaves biomass
      were fit on the Freundlich and Langmuir adsorption isotherms at 297 K. The Cd(II)
      and Cr(III) solutions were adjusted to pH 5.0 and the Cr(VI) solution was
      adjusted to pH 2.0. The correlation coefficient values indicated that the data
      fit better the Freundlich model. The maximal capacities (K(F)) were found to be
      5.79 x 10(-2), 3.25 x 10(-2), and 1.14 x 10(-2) mol/g for Cr(III), Cd(II), and
      Cr(VI), respectively. Similar results were obtained using the Langmuir and the
      Dubinin-Radushkevick equations. Thermodynamic parameters calculated from the Khan
      and Singh equation and from the q(e) vs C(e) plot show that the equilibrium
      constants for the biosorption of the metals follow the same order of the maximal
      capacities. The negative Gibbs free energy values obtained for Cd(II) and Cr(III)
      indicated that these ions were biosorbed spontaneously. The mean free energy
      values calculated from the Dubinin-Radushkevick equation (10.78, 9.45, and 9.05
      for Cr(III), Cr(VI), and Cd(II), respectively) suggest that the binding of
      Cd(II), Cr(III), and Cr(VI) by saltbush leaves biomass occurs through an ionic
      exchange mechanism.

PMID- 16600279
TI  - Stability of the aqueous suspensions of nanotubes in the presence of nonionic
      surfactant.
AB  - Stability of aqueous suspensions of multiwalled carbon nanotubes (MWNTs) and
      their percolation behavior are investigated. Nanotubes of aqueous suspensions
      show a strong tendency to aggregation and networking into electroconductive
      clusters. The percolation threshold of the electrical conductivity is rather low
      and of order phi approximately 0.01 (where phi is the volume fraction), which can
      be explained by the high aspect ratio of MWNTs. Strong influence of the nonionic
      surfactant Triton X-305 on the colloidal stability of aqueous suspensions of
      MWNTs is observed. Addition of surfactant exerts a stabilizing effect at
      surfactant concentration C(s) proportional to the weight concentration C of
      MWNTs, C(s) approximately C mol/dm3. The transient behavior of electrical
      conductivity in the aqueous suspensions is explained by fractal aggregation
      processes. The fractal dimension is shown to be sensitive to the surfactant
      concentration C(s).

PMID- 16600280
TI  - Kinetics of polyelectrolyte adsorption onto polystyrene latex particle studied
      using electrophoresis: effects of molecular weight and ionic strength.
AB  - The kinetics of the adsorption of a cationic polymer flocculant onto negatively
      charged polystyrene latex (PSL) particles were measured by means of
      electrophoresis as a function of the molecular weight of the polyelectrolyte and
      the ionic strength of the solution. In the experiment, the dispersion of bare PSL
      particles was mixed with a polyelectrolyte solution by means of end-over-end
      rotation in which the mixing intensity was evaluated in terms of the collision
      frequency between the colloidal particles. The rate of electrophoretic mobility
      of a PSL particle, which remained as a singlet, was measured against the mixing
      steps, which was equivalent to the time elapsed after the onset of flocculation.
      The shape of the kinetic curves is typical: a linear increase for a short period
      followed by a plateau, implying the saturation of the colloidal surface by the
      adsorbed polyelectrolyte. In the case of low ionic strength, the plateau value
      was dependent on the molecular weight of the polyelectrolyte. That is, a lower
      plateau value was detected when the molecular weight of the polyelectrolyte was
      smaller and its concentration was lower. However, the amount of adsorption was
      kinetically controlled only for the case of higher molecular weight. In the case
      of high ionic strength, the plateau value of electrophoresis was constant,
      regardless of the polyelectrolyte concentration and molecular weight. These data
      will ultimately be useful in further analysis of the flocculation behavior of
      colloidal particles with a polyelectrolyte.

PMID- 16600281
TI  - The adsorption and unfolding kinetics determines the folding state of proteins at
      the air-water interface and thereby the equation of state.
AB  - Unfolding of proteins has often been mentioned as an important factor during the
      adsorption process at air-water interfaces and in the increase of surface
      pressure at later stages of the adsorption process. This work focuses on the
      question whether the folding state of the adsorbed protein depends on the rate of
      adsorption to the interface, which can be controlled by bulk concentration.
      Therefore, the adsorption of proteins with varying structural stabilities at
      several protein concentrations was studied using ellipsometry and surface
      tensiometry. For beta-lactoglobulin the adsorbed amount (Gamma) needed to reach a
      certain surface pressure (Pi) decreased with decreasing bulk concentration.
      Ovalbumin showed no such dependence. To verify whether this difference in
      behavior is caused by the difference in structural stability, similar experiments
      were performed with cytochrome c and a destabilized variant of this protein. Both
      proteins showed identical Pi-Gamma, and no dependence on bulk concentration. From
      this work it was concluded that unfolding will only take place if the kinetics of
      adsorption is similar or slower than the kinetics of unfolding. The latter
      depends on the activation energy of unfolding (which is in the order of 100-300
      kJ/mol), rather than the free energy of unfolding (typically 10-50 kJ/mol).

PMID- 16600282
TI  - Aging of oil-in-water emulsions: the role of the oil.
AB  - Controlling stability and aging of emulsions is important from commercial and
      scientific perspectives. Achieving such control comes through gaining an
      understanding of the relationship between emulsion constituents and
      microstructure and how these influence the kinetics and mechanism of
      destabilisation. We present here an investigation determining the rate of
      destabilisation as a function of time for a series of water/n-alkane/Triton X-100
      oil-in-water emulsions. The time dependence of the emulsions was investigated
      using static light scattering, PFG-NMR and measurement of gross phase separation.
      By changing the chain length of the oil from hexane to tetradecane, an almost
      five orders of magnitude variation in emulsion lifetime could be achieved, while
      maintaining most of the other chemical and physical characteristics of the
      emulsions. Further, we show that while Ostwald ripening is the dominant
      destabilisation mechanism, two distinct regimes are evident. Initially, we
      observed an enhanced Ostwald ripening regime due to the presence of oil-swollen
      micelles in the aqueous continuum, that is a depletion flocculation mechanism is
      followed. The presence of oil-swollen micelles was confirmed using PFG-NMR. The
      micelles aid the gross oil transport between the discrete oil domains. Upon phase
      separation the oil-swollen micelles are predominantly removed from the emulsion
      along with the excess water resulting in a concomitant reduction in the ripening
      rate, producing the more general Ostwald ripening cubic dependence of droplet
      radius as a function of time for the lower molecular weight oils. The oils with
      higher molecular weight (decane and above), however, were observed to switch over
      to destabilisation via creaming. PFG-NMR was shown to be a powerful technique to
      fully probe emulsion microstructure as a function of time with droplet size and
      spacing being directly obtained from the data.

PMID- 16600283
TI  - Color, reference, and expertise in language acquisition.
AB  - In learning the meaning of a new term, children need to fix its reference, learn
      its conventional meaning, and discover the meanings with which it contrasts. To
      do this, children must attend to adult speakers--the experts--and to their
      patterns of use. In the domain of color, children need to identify color terms as
      such, fix the reference of each one, and learn how each is used in the language.
      But color is a property, and terms for properties appear to be more difficult to
      grasp than do those for objects, actions, and relations. Although children find
      some domains easier to learn than others, they depend in each case on the
      expertise of adult speakers.

PMID- 16600284
TI  - Constraints on children's color term acquisition.
AB  - Kowalski and Zimiles (2006) and O'Hanlon and Roberson (2006) address an age-old
      question: Why do children find it difficult to learn color terms? Here these
      articles are reflected on, providing a focused examination of the issues central
      to this question. First, the criteria by which children are said to find color
      naming difficult are considered. Although the age of color term acquisition is
      decreasing, and color naming might not be more difficult than other abstract
      attributes, several stages of difficulty are identified. Second, it is argued
      that there are potentially multiple constraints (e.g., conceptual, attentional,
      and linguistic) for these multiple stages of difficulty with color term
      acquisition. Third, it is argued that the validity and reliability of techniques
      for identifying constraints need to be considered and that converging evidence
      for the constraints should be provided. Finally, a series of new questions that
      need to be asked to provide a well-rounded explanation of the difficulties
      children face when learning color terms is outlined.

PMID- 16600285
TI  - The role of discourse context in developing word form representations: a
      paradoxical relation between reading and learning.
AB  - To acquire representations of printed words, children must attend to the written
      form of a word and link this form with the word's pronunciation. When words are
      read in context, they may be read with less attention to these features, and this
      can lead to poorer word form retention. Two experiments with young children (ages
      5-8 years) confirmed this hypothesis. In our experiments, children attempted to
      read words they could not previously read, during a self-teaching period, either
      in context or in isolation. Later they were tested on how well they learned the
      words as a function of self-teaching condition (isolation or context). Consistent
      with previous research, children read more words accurately in context than in
      isolation during self-teaching; however, children had better retention for words
      learned in isolation. Furthermore, this benefit from learning in isolation was
      larger for less skilled readers. This effect of poorer word retention when words
      are learned in context is paradoxical because context has been shown to
      facilitate word identification. We discuss factors that may influence this effect
      of context, especially the role of children's skill level and the demands of
      learning new word representations at the beginning of reading instruction.

PMID- 16600286
TI  - Potential role for gut microbiota in cell wall digestion and glucoside
      detoxification in Tenebrio molitor larvae.
AB  - Tenebrio molitor larvae were successfully reared free of cultivatable gut lumen
      bacteria, yeasts and fungi using two approaches; aseptic rearing from surface
      sterilized eggs and by feeding larvae with antibiotic-containing food. Insects
      were reared on a rich-nutrient complete diet or a nutrient-poor refractory diet.
      A comparison of digestive enzyme activities in germ free and conventional insects
      containing a gut microbiota did not reveal gross differences in enzymes that
      degrade cell walls from bacteria (lysozyme), fungi (chitinase and laminarinase)
      and plants (cellulase and licheninase). This suggested that microbial-derived
      enzymes are not an essential component of the digestive process in this insect.
      However, more detailed analysis of T. molitor midgut proteins using an
      electrophoretic separation approach showed that some digestive enzymes were
      absent and others were newly expressed in microbiota-free larvae. Larvae reared
      in antibiotic-containing refractory wheat bran diet performed poorly in
      comparison with controls. The addition of saligenin, the aglycone of the plant
      glucoside salicin, has more deleterious effects on microbiota-free larvae than on
      the conventionally reared larvae, suggesting a detoxifying role of midgut
      microbiota. Analysis of the volatile organic compounds released from the faecal
      pellets of the larvae shows key differences in the profiles from conventionally
      reared and aseptically reared larvae. Pentadecene is a semiochemical commonly
      found in other beetle species. Here we demonstrate the absence of pentadecene
      from aseptically reared larvae in contrast to its presence in conventionally
      reared larvae. The results are discussed in the light of the hypothesis that
      microbial products play subtle roles in the life of the insect, they are involved
      in the digestion of refractory food, detoxification of secondary plant compounds
      and modify the volatile profiles of the insect host.

PMID- 16600287
TI  - Human atrial conduction and arrhythmogenesis correlates with conformational
      exposure of specific epitopes on the connexin40 carboxyl tail.
AB  - BACKGROUND: Gap junction expression is considered to influence myocardial
      conduction and arrhythmogenesis, but studies in patients with atrial fibrillation
      (AF) have reported inconsistent results. We used human atrial conduction and
      arrhythmogenicity to provide clinical parameters with which to correlate
      quantification of connexin40 (Cx40) by different techniques to address the
      hypothesis that antibody-epitope binding properties may influence quantification
      methods. METHODS AND RESULTS: Atrial conduction properties were studied in
      patients undergoing coronary artery bypass grafting (N = 27) using multi
      electrode array mapping. Patients were defined as having a vulnerable atrial
      substrate if pacing-induced AF lasted for more than 30 s. Using antibodies
      targeted at two different epitopes of the cytoplasmic carboxyl tail, Cx40 signal
      was quantified by immunoconfocal microscopy in biopsies taken from the mapped
      atria. Only patients with a vulnerable substrate subsequently developed post
      operative AF (P < 0.02). Immunoconfocal Cx40 signal measured by one antibody,
      designated S15C(R85), was lower in patients with sustained induced AF (0.013 +/-
      0.009 microm(2)/microm(2) vs. 0.024 +/- 0.010 microm(2)/microm(2), P = 0.005) and
      was negatively correlated with atrial conduction velocity during sinus rhythm (P
      < 0.05). However, these relationships did not exist when the Cx40 signal was
      measured using a different antibody (Y21Y(R968)). Further studies suggested that
      quantification technique was reproducible against the same epitope (P < 0.001)
      but not against different epitopes indicating variable exposure of Cx40 epitopes.
      CONCLUSIONS: Quantification of Cx40 by immunoconfocal microscopy appears to be
      epitope dependent and evidence of epitope masking raises the possibility of more
      than one conformational form of the Cx40 carboxyl tail, suggesting functionally
      important conformations of the protein.

PMID- 16600288
TI  - Histidine-rich Ca binding protein: a regulator of sarcoplasmic reticulum calcium
      sequestration and cardiac function.
AB  - Defects in the pathways that regulate cardiac sarcoplasmic reticulum (SR) calcium
      (Ca) cycling represent prime targets for driving the deterioration of function
      and progression to heart failure. We hypothesized that the histidine-rich Ca
      binding protein (HRC) in the SR may be involved in SR Ca cycling and that
      alterations in HRC levels would result in abnormal cardiac Ca homeostasis. In
      order to test this hypothesis, we generated transgenic mice with cardiac
      overexpression (3-fold) of HRC. Increased cardiac HRC levels were associated with
      impaired SR Ca uptake rates (35%) and attenuated cardiomyocyte Ca transient decay
      (38%), without alterations in peak Ca transients or SR Ca load. The depressed SR
      Ca sequestration was associated with attenuated rate of Ca extrusion via Na-Ca
      exchange. Triadin protein expression levels and L-type Ca channel current density
      were increased, while the channel inactivation kinetics were not altered.
      Impaired SR Ca uptake and delayed Ca decline rates triggered hypertrophy and
      compromised the heart's responses to increased stress by either hemodynamic
      overload or the aging process. By 18 months of age, cardiac remodeling
      deteriorated to congestive heart failure in transgenic mice. Collectively, these
      data suggest that HRC may be an integral regulatory protein involved in cardiac
      muscle SR Ca uptake and Ca homeostasis.

PMID- 16600289
TI  - Down regulation of the L-type Ca2+ channel, GRK2, and phosphorylated
      phospholamban: protective mechanisms for the denervated failing heart.
AB  - We previously found that a canine model of selective surgical ventricular
      denervation (VD), which does not permit increased sympathetic tone during the
      pathogenesis of heart failure (HF), tolerated the development of HF better than
      controls. To investigate the cellular mechanisms, we examined cellular
      contraction and L-type Ca(2+) channel currents (I(Ca)) and their responses to
      beta-adrenergic receptor (beta-AR) stimulation in left ventricular myocytes from
      1) control, 2) VD, 3) HF induced by rapid pacing, and 4) HF induced in VD (VD-HF)
      dogs. The magnitude of myocyte contraction and rate of relaxation in VD were
      similar to control but were depressed in both HF and VD-HF. These changes were
      associated with reduced protein expression of sarcoplasmic reticulum Ca(2+)
      ATPase (SERCA2a) and protein kinase A phosphorylated phospholamban (PLB), which
      was reduced in HF, but essentially abolished in VD-HF. beta-AR kinase (GRK2) was
      increased in HF but reduced in VD-HF. Basal I(Ca) density did not differ among
      control, VD, and HF groups, but VD-HF myocytes showed a markedly reduced I(Ca)
      density (approximately 40%). Compared to controls, the sensitivity of I(Ca) to
      isoproterenol (ISO), was significantly higher in VD, but reduced in HF. While
      I(Ca) responses to ISO in VD-HF were maintained at control levels, the amplitude
      of the ISO-stimulated I(Ca) was significantly smaller (approximately 50%)
      compared with HF myocytes. The relative decrease in Ca(2+) influx due to
      downregulation of I(Ca) density may contribute to the cardioprotective effects in
      VD-HF hearts by preventing Ca(2+) overload during the development of HF. These
      findings, in combination with the virtual abolition of phosphorylated PLB in VD
      HF and the decrease in GRK2, may explain, in part, why VD dogs tolerate the
      development of HF better than control dogs.

PMID- 16600290
TI  - Homocysteine accelerates senescence and reduces proliferation of endothelial
      progenitor cells.
AB  - Our previous studies showed that homocysteine (Hcy) reduces endothelial
      progenitor cell (EPC) numbers and impairs functional activity. However, the
      mechanisms by which Hcy reduces EPCs numbers and activity remain to be
      determined. Recent studies have demonstrated that reduced EPCs numbers and
      activity was associated with EPCs senescence which involved telomerase activity.
      Therefore, we investigated whether Hcy accelerates the onset of EPCs senescence
      through telomerase inactivation, leading to cellular dysfunction. EPCs were
      isolated from peripheral blood and characterized. After ex vivo cultivation, EPCs
      became senescent as determined by acidic beta-galactosidase staining. Hcy dose
      dependently accelerated the onset of EPCs senescence in culture. Moreover, Hcy
      decreased proliferation of EPCs as assessed by BrdU incorporation assay and
      colony-forming capacity. To get further insights into the underlying mechanisms
      of these effects induced by Hcy, we measured telomerase activity and determined
      the phosphorylation of Akt by using western blot. Hcy significantly diminished
      telomerase activity and Akt phosphorylation. Taken together, the results of the
      present study demonstrated that Hcy accelerated the onset of EPCs senescence,
      leading to cellular dysfunction. The effect of Hcy might be dependent on
      telomerase inactivation, and Akt dephosphorylation also appeared to play a major
      role. In addition, atorvastatin had a preventative effect against Hcy-induced
      EPCs senescence.

PMID- 16600291
TI  - Cross-bridge dependent cooperativity determines the cardiac force-length
      relationship.
AB  - Opinions vary as to whether the dominant cooperativity mechanism, modulating the
      cardiac force-length-calcium relationships, depends on sarcomere length (SL),
      force, or calcium. We hypothesize that separately characterizing the dependence
      of the delay in the force response to length oscillations on SL, force and
      calcium allows testing these hypotheses; Oscillations imposed at the same SL,
      utilizing various calcium concentrations, entail similar delay if the
      cooperativity is exclusively length dependent. Oscillations at constant tetanic
      force, utilizing various SLs and calcium levels, entail similar delay when the
      cooperativity is exclusively force dependent. Force responses to large (102 +/-
      13 nm/sarcomere) oscillations, at different SLs, extracellular calcium
      concentrations ([Ca(2+)](o)s) and force, were studied in intact tetanized
      trabeculae, dissected from rats' right ventricles (N = 11). Tetanii (3.5 s) were
      obtained by utilizing cyclopiazonic acid (K-H, 25 degrees C). SL was measured by
      laser diffraction. Force responses to length oscillations lagged behind the
      length oscillations at short SL and low [Ca(2+)](o), yielding counterclockwise
      hystereses in the force-length plane: the force was higher during shortening than
      during lengthening. The area within the counterclockwise hysteresis represents
      the external work that originates from XB recruitment, and it increases as the
      phase delay increases. The phase decreases by 25.7 +/- 17.0 degrees for 0.1
      microm sarcomere lengthening, at constant [Ca(2+)](o) (e.g. 45 +/- 9 degrees and
      22 +/- 13 degrees for SL=1.89 +/- 0.01 and 1.99 +/- 0.01 microm, respectively,
      [Ca(2+)](o) = 3 mM). The phase decrease by 15 +/- 5.7 degrees for an increase of
      1.5 mM in [Ca(2+)](o), at constant SL. However, maintaining the same force with
      different pairs of [Ca(2+)](o) and SL yields identical phase. The direct
      dependence of the phase on force indicates that XB recruitment is determined
      directly by the force and only indirectly by SL or calcium. The dominant cardiac
      cooperativity is determined by the number of strong XBs.

PMID- 16600292
TI  - Cause of death: a "broken" MEKK?

PMID- 16600293
TI  - Modulation of action potential duration on myocyte hypertrophic pathways.
AB  - Prolongation of the action potential duration (APD) has consistently been
      observed in experimental models of cardiac hypertrophy and failure as well as in
      humans and is partially attributed to a reduction of a hyperpolarizing current
      provided by the calcium-independent transient outward K(+) channel (I(to)). In
      the present study, we examined the effects of manipulating ion channel currents
      (I(to) and sodium/calcium exchanger (NCX)) and the associated alterations in
      action potential duration on cardiomyocyte hypertrophy and signaling induced by
      angiotensin II (AngII). Our aim was to examined whether distinct patterns of
      intracellular calcium manipulation could generate distinct patterns of MAPkinase
      activation and cellular hypertrophy. Cultured neonatal rat ventricular myocytes
      (NRVMs) were infected with Ad. beta-gal/GFP, Ad.Kv4.3, Ad.Kv4.3 antisense or
      Ad.NCX adenoviruses and hypertrophy induced by incubation with AngII.
      Overexpression of Kv4.3 increased I(to) density, shortened APD, decreased Ca(2+)
      influx and inhibited AngII-induced (3)H-leucine incorporation and ANF and beta
      MHC expression. These hypertrophic changes were also paralleled by blockade of
      ERK MAP kinases activation as well as calcineurin expression. These electrical
      and hypertrophic changes produced by overexpression of Kv4.3 were completely and
      significantly reversed by Kv4.3 antisense and NCX gene transfer. Our findings
      indicate that AngII-mediated hypertrophy response in NRVMs can be abrogated by an
      enhancement of I(to) function through overexpression of Kv4.3 and that modulation
      of action potential duration can be important in the development of cardiac
      hypertrophy.

PMID- 16600294
TI  - Thermal adaptation of the yeast mitochondrial Hsp70 system is regulated by the
      reversible unfolding of its nucleotide exchange factor.
AB  - The Hsp70 protein switches during its functional cycle from an ADP-bound state
      with a high affinity for substrates to a low-affinity, ATP-bound state, with
      concomitant release of the client protein. The rate of the chaperone cycle is
      regulated by co-chaperones such as nucleotide exchange factors that significantly
      accelerate the ADP/ATP exchange. Mge1p, a mitochondrial matrix protein with
      homology to bacterial GrpE, serves as the nucleotide exchange factor of
      mitochondrial Hsp70. Here, we analyze the influence of temperature on the
      structure and functional properties of Mge1p from the yeast Saccharomyces
      cerevisiae. Mge1p is a dimer in solution that undergoes a reversible thermal
      transition at heat-shock temperatures, i.e. above 37 degrees C, that involves
      protein unfolding and dimer dissociation. The thermally denatured protein is
      unable to interact stably with mitochondrial Hsp70, and therefore is unable to
      regulate its ATPase and chaperone cycle. Crosslinking of wild-type mitochondria
      reveals that Mge1p undergoes the same dimer to monomer temperature-dependent
      shift, and that the nucleotide exchange factor does not associate with its Hsp70
      partner at stress temperatures (i.e. > or =45 degrees C). Once the stress
      conditions disappear, Mge1p refolds and recovers both structure and functional
      properties. Therefore, Mge1p can act as a thermosensor for the mitochondrial
      Hsp70 system, regulating the nucleotide exchange rates under heat shock, as has
      been described for two bacterial GrpE proteins. The thermosensor activity is
      conserved in the GrpE-like nucleotide exchange factors although, as discussed
      here, it is achieved through a different structural mechanism.

PMID- 16600295
TI  - Crystal structure of isoflavone reductase from alfalfa (Medicago sativa L.).
AB  - Isoflavonoids play important roles in plant defense and exhibit a range of
      mammalian health-promoting activities. Isoflavone reductase (IFR) specifically
      recognizes isoflavones and catalyzes a stereospecific NADPH-dependent reduction
      to (3R)-isoflavanone. The crystal structure of Medicago sativa IFR with deletion
      of residues 39-47 has been determined at 1.6A resolution. Structural analysis,
      molecular modeling and docking, and comparison with the structures of other NADPH
      dependent enzymes, defined the putative binding sites for co-factor and substrate
      and potential key residues for enzyme activity and substrate specificity. Further
      mutagenesis has confirmed the role of Lys144 as a catalytic residue. This study
      provides a structural basis for understanding the enzymatic mechanism and
      substrate specificity of IFRs as well as the functions of IFR-like proteins.

PMID- 16600296
TI  - Crystal structure of full length topoisomerase I from Thermotoga maritima.
AB  - DNA topoisomerases are a family of enzymes altering the topology of DNA by
      concerted breakage and rejoining of the phosphodiester backbone of DNA. Bacterial
      and archeal type IA topoisomerases, including topoisomerase I, topoisomerase III,
      and reverse gyrase, are crucial in regulation of DNA supercoiling and maintenance
      of genetic stability. The crystal structure of full length topoisomerase I from
      Thermotoga maritima was determined at 1.7A resolution and represents an intact
      and fully active bacterial topoisomerase I. It reveals the torus-like structure
      of the conserved transesterification core domain comprising domains I-IV and a
      tightly associated C-terminal zinc ribbon domain (domain V) packing against
      domain IV of the core domain. The previously established zinc-independence of the
      functional activity of T.maritima topoisomerase I is further supported by its
      crystal structure as no zinc ion is bound to domain V. However, the structural
      integrity is preserved by the formation of two disulfide bridges between the four
      Zn-binding cysteine residues. A functional role of domain V in DNA binding and
      recognition is suggested and discussed in the light of the structure and previous
      biochemical findings. In addition, implications for bacterial topoisomerases I
      are provided.

PMID- 16600297
TI  - Artemis phosphorylated by DNA-dependent protein kinase associates preferentially
      with discrete regions of chromatin.
AB  - Artemis is a nuclear phosphoprotein required for genomic integrity whose
      phosphorylation is increased subsequent to DNA damage. Artemis phosphorylation by
      the DNA-dependent protein kinase (DNA-PK) and the association of Artemis with DNA
      PK catalytic subunit (DNA-PKcs) have been proposed to be crucial for the
      variable, diversity, joining (V(D)J) reaction, genomic stability and cell
      survival in response to double-stranded DNA breaks. The exact nature of the
      effectors of Artemis phosphorylation is presently being debated. Here, we have
      delimited the interface on Artemis required for its association with DNA-PKcs and
      present the characterization of six DNA-PK phosphorylation sites on Artemis whose
      phosphorylation shows dependence on its association with DNA-PKcs and is induced
      by double-stranded DNA damage. Surprisingly, DNA-PKcs Artemis association
      appeared to be dispensable in a V(D)J recombination assay with stably integrated
      DNA substrates. Phosphorylation at two of the sites on Artemis, S516 and S645,
      was verified in vivo using phosphospecific antibodies. Basal Artemis S516 and
      S645 phosphorylation in vivo showed a significant dependence on DNA-PKcs
      association. However, regardless of its association with DNA-PKcs,
      phosphorylation of Artemis at both S516 and S645 was stimulated in response to
      the double-stranded DNA-damaging agent bleomycin, albeit to a lesser extent. This
      suggests that additional factors contribute to promote DNA damage-induced Artemis
      phosphorylation. Intriguingly, pS516/pS645 Artemis was concentrated in chromatin
      associated nuclear foci in naive cells. These foci were maintained upon DNA
      damage but failed to overlap with the damage-induced gammaH2AX. These results
      provide the expectation of a specific role for DNA-PK-phosphorylated Artemis in
      both naive and damaged cells.

PMID- 16600298
TI  - Metabolic alterations in the dorsolateral prefrontal cortex after treatment with
      high-frequency repetitive transcranial magnetic stimulation in patients with
      unipolar major depression.
AB  - Neuroimaging studies suggest a specific role of anterior cingulate cortex (ACC)
      and left dorsolateral prefrontal cortex (DLPFC) in major depression. Stimulation
      of the latter by means of repetitive transcranial magnetic stimulation (rTMS) as
      an antidepressant intervention has increasingly been investigated in the past.
      The objective of the present study was to examine in vivo neurochemical
      alterations in both brain regions in 17 patients with unipolar major depression
      before and after 10 days of high-frequency (20Hz) rTMS of the left DLPFC using 3
      tesla proton magnetic resonance spectroscopy. Six out of seventeen patients were
      treatment responders, defined as a 50% reduction of the Hamilton depression
      rating scale. No neurochemical alterations in the ACC were detected after rTMS.
      As compared to the non-responders, responders had lower baseline concentrations
      of DLPFC glutamate which increased after successful rTMS. Correspondingly,
      besides a correlation between clinical improvement and an increase in glutamate
      concentration, an interaction between glutamate concentration changes and
      stimulation intensity was observed. Our results indicate that metabolic, state
      dependent changes within the left DLPFC in major depressive disorder involve the
      glutamate system and can be reversed in a dose-dependent manner by rTMS.

PMID- 16600299
TI  - Plasma cytokines profile in older subjects with late onset Alzheimer's disease or
      vascular dementia.
AB  - Some cytokines have been involved in the pathogenesis of late onset Alzheimer's
      disease (LOAD). A possible increase in plasma cytokines levels has been reported
      in LOAD and vascular dementia (VD), but the results of previous studies are
      conflicting. We evaluated the plasma levels of IL-6, TNF-alpha, IL-1beta, and IL
      10 in four groups of older individuals: 60 patients with LOAD, 80 patients with
      VD, 40 subjects with cerebrovascular disease but without dementia (CDND), and 42
      controls (C). By analysis of covariance (adjustment for age, gender, coronary
      heart disease, diabetes, hypertension, smoking, and alcohol consumption) we found
      that: *IL-1beta was higher in VD, LOAD, and CDND compared with controls
      (p<0.005). *TNF-alpha was higher in VD and LOAD compared to C (p<0.05), and in VD
      compared to LOAD (p<0.03). *IL-6 was higher in VD compared with LOAD (p<0.03). No
      differences in IL-10 values were found (Kruskal-Wallis, Asymp. Sig. 0.14). By
      logistic regression analysis, we demonstrated that high levels (defined as above
      the median) of IL-1beta and TNF-alpha, but not of IL-6, were associated with
      increased likelihood of having VD and LOAD compared to C, while high IL-6 levels
      were associated with a increased probability of having VD, compared with LOAD.
      Our study support the notion of a low-grade systemic inflammation in older
      patients with LOAD or VD, characterized by an increase in plasma IL-1beta and TNF
      alpha levels. The high IL-6 levels found in VD might be not a specific finding,
      as it might come from several conditions including atherosclerosis and related
      vascular risk factors, comorbidity, and frailty.

PMID- 16600300
TI  - Increased lipid peroxidation and neuron specific enolase in treatment refractory
      schizophrenics.
AB  - It is well-known that increased lipid peroxidation and failure of antioxidant
      mechanisms leads to neuronal damage in schizophrenic patients. However, this
      neurodegenerative mechanism has not been studied in treatment refractory
      schizophrenics (TRS). Therefore, the main purpose of this study was to determine
      neuronal damage in TRS in comparison to non-refractory schizophrenics (NRS) by
      means of quantitative analysis of lipid peroxidation and neuron specific enolase
      (NSE) related to the psychopathology severity. Two groups of paranoid
      schizophrenics, TRS and NRS, and a group of healthy controls (CO) were assembled
      (n=13). Lipid peroxidation was analyzed through spectrophotometry for
      quantification of malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) serum
      concentrations. As well, serum NSE was quantified by radioimmunoassay (ELSA).
      Psychopathology was evaluated using the brief psychiatric rating scale (BPRS) and
      the positive and negative symptoms scale (PANSS). TRS showed significant higher
      concentrations of lipoperoxides by-products and NSE, than NRS and CO. Clinical
      scores also revealed a more severe pathology in TRS, than in NRS. Raised
      lipoperoxidation correlated with higher delusions and emotional withdrawal
      symptoms, and increased NSE correlated with a lower flow of the conversation and
      lack of spontaneity. All these results together suggest that TRS patients suffer
      a greater lipid peroxidation and neuronal damage than NRS, apparently related to
      worsening of some of the psychiatric symptoms.

PMID- 16600301
TI  - Increased BDNF serum concentration in fibromyalgia with or without depression or
      antidepressants.
AB  - Fibromyalgia (FM) is still often viewed as a psychosomatic disorder. However, the
      increased pain sensitivity to stimuli in FM patients is not an "imagined"
      histrionic phenomena. Pain, which is consistently felt in the musculature, is
      related to specific abnormalities in the CNS pain matrix. Brain-derived
      neurotrophic factor (BDNF) is an endogenous protein involved in neuronal survival
      and synaptic plasticity of the central and peripheral nervous system (CNS and
      PNS). Several lines of evidence converged to indicate that BDNF also participates
      in structural and functional plasticity of nociceptive pathways in the CNS and
      within the dorsal root ganglia and spinal cord. In the latter, release of BDNF
      appears to modulate or even mediate nociceptive sensory inputs and pain
      hypersensitivity. We were interested, if BDNF serum concentration may be altered
      in FM. The present pilot study assessed to our knowledge for the first time BDNF
      serum concentrations in 41 FM patients in comparison to 45 age-matched healthy
      controls. Mean serum levels of BDNF in FM patients (19.6 ng/ml; SD 3.1) were
      significantly increased as compared to healthy controls (16.8 ng/ml; SD 2.7;
      p<0.0001). In addition, BDNF serum concentrations in FM patients were independent
      from age, gender, illness duration, preexisting recurrent major depression and
      antidepressive medication in low doses. In conclusion, the results from our study
      indicate that BDNF may be involved in the pathophysiology of pain in FM.
      Nevertheless, how BDNF increases susceptibility to pain is still not known.

PMID- 16600302
TI  - Negative inotropic effects of C-type natriuretic peptide are attenuated in
      hypertrophied ventricular myocytes associated with reduced cyclic GMP production.
AB  - BACKGROUND: We tested the hypothesis that the negative inotropic effects of C
      type natriuretic peptide (CNP) would be diminished in renal hypertensive (one
      kidney-one-clip, 1K1C) hypertrophic rabbit hearts and that this attenuated effect
      would be due either to decreased cyclic GMP production or to reduced signaling.
      MATERIAL AND METHODS: Using isolated control and 1K1C ventricular myocytes, cell
      shortening data (video edge detection) were collected: (1) at baseline and after
      CNP 10(-8,-7) M, followed by KT5823 (KT), a cyclic GMP-dependent protein kinase
      inhibitor; or (2) at baseline, following KT pre-treatment and subsequent CNP 10(
      8,-7) M. In addition, cyclic GMP levels were determined by radioimmunoassay at
      baseline and CNP 10(-7) M. RESULTS: In control myocytes, CNP decreased percent
      shortening (5.7 +/- 0.4 versus 4.0 +/- 0.4% at 10(-7) M), maximal rate of
      shortening (58.7 +/- 5.1 versus 45.2 +/- 3.6 microm/sec) and maximal rate of
      relaxation (57.1 +/- 4.9 versus 44.1 +/- 3.4 microm/sec) in a concentration
      dependent manner. These effects were attenuated by subsequent KT administration.
      CNP failed to produce these negative functional effects in 1K1C myocytes. When
      pre-treated with KT, CNP had no negative functional effect in either normal and
      1K1C myocytes. Basal levels of cyclic GMP were similar in control versus 1K1C
      myocytes; however, CNP produced a significant rise in cyclic GMP level in control
      (63.6 +/- 7.8 versus 83.5 +/- 11.3 pmol/10(5) myocytes) but not in 1K1C (49.2 +/-
      2.6 versus 52.7 +/- 5.6) myocytes. CONCLUSIONS: Thus, CNP acted through the
      cyclic GMP protein kinase in control myocytes. We conclude that in hypertrophic
      cardiac myocytes, the decreased effect of CNP was because of decreased production
      of cyclic GMP.

PMID- 16600304
TI  - Interaction between stromal fibroblasts and colorectal cancer cells in the
      expression of vascular endothelial growth factor.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF), a potent angiogenic
      factor, has been implicated in metastasis of colorectal cancer (CRC). The present
      study aimed to clarify whether cancer-stromal interaction induces the production
      of VEGF. MATERIALS AND METHODS: Human colonic fibroblasts (CCD-18Co) and CRC
      (SW480, SW620) cells were analyzed in this study. The cell cycle of colonic
      fibroblasts during co-culture was analyzed by flow cytometry. VEGF and TGF-beta1
      released into the conditioned media in co-culture models were measured. Northern
      blot with human specific VEGF probe was performed to identify the expression of
      VEGF in this model. RESULTS: Co-culture of colonic fibroblasts with CRC cells
      increased the viability of fibroblasts during co-culture. Cell cycle analysis
      revealed that most of the fibroblasts co-cultured with CRC cells were arrested at
      G1 phase and few cells were in sub-G1 phase that indicates apoptosis. Although
      VEGF protein was detected in the culture media of all of the monocultures, co
      cultivation of CRC with fibroblasts resulted in synergistic increase of VEGF
      production compared with monocultures. However TGF-beta1 protein was not detected
      in any conditioned medium. VEGF mRNA was detected in both CRC and fibroblasts.
      Under co-culture condition, an abundance of VEGF mRNA expression was noted in
      fibroblasts relative to CRC cells. CONCLUSIONS: The present study suggests that
      CRC manipulates the host stroma to suppress apoptosis and up-regulate VEGF
      production.

PMID- 16600305
TI  - Heat shock preconditioning inhibits CD4+ T lymphocyte activation in transplanted
      fatty rat livers.
AB  - Heat shock preconditioning (HPc) of fatty donor livers significantly increases
      recipient survival in rats. We investigated to what extent the blockade of
      Kupffer cells by gadolinium chloride (GdCl3) can mimic the effect of HPc and the
      involvement of liver CD4+ T lymphocytes in HPc. Fatty liver was experimentally
      induced in Lewis rats by a choline- and methionine-deficient diet. Fatty liver
      donors were pretreated with HPc (42.5 degrees C for 10 min), the Kupffer cell
      inhibitor GdCl3, or placebo (sham group). Donors were then harvested, stored in
      University of Wisconsin preservation solution for 12 h at 4 degrees C, and
      transplanted into normal syngeneic rats. Hepatic injury (alanine
      aminotransferase) and serum cytokines (interleukin-12p70, tumor necrosis factor
      alpha, and interleukin-10) of recipients increased at 3 h, then decreased, and
      increased again at 24 h after transplantation. HPc treatment diminished both the
      early and later phases of this biphasic response and improved recipient survival.
      GdCl3 reduced these cytokines in the early but not the later phase and did not
      reduce neutrophil accumulation or improve the recipient survival. HPc, but not
      GdCl3 treatment, also reduced the number of liver CD4+ T lymphocytes and their
      interferon-gamma production. We conclude that HPc, but not GdCl3 treatment,
      prevents biphasic liver injury and the activation of liver CD4+ T lymphocytes in
      transplanted fatty donor livers.

PMID- 16600307
TI  - Actin filament branching and protrusion velocity in a simple 1D model of a motile
      cell.
AB  - We formulate and analyse a 1D model for the spatial distribution of actin density
      at the leading edge of a motile cell. The model incorporates nucleation, capping,
      growth and decay of actin filaments, as well as retrograde flow of the actin
      meshwork and known parameter values based on the literature. Using a simplified
      geometry, and reasonable assumptions about the biochemical processes, we derive
      PDEs for the density of actin filaments and their tips. Analytic travelling wave
      solutions are used to predict how the speed of the cell depends on rates of
      nucleation, capping, polymerization and membrane resistance. Analysis and
      simulations agree with experimental profiles for measured actin distributions.
      Extended versions of the model are studied numerically. We find that our model
      produces stable travelling wave solutions with reasonable cell speeds. Increasing
      the rate of nucleation of filaments (by the actin related protein Arp2/3) or the
      rate of actin polymerization leads to faster cell speed, whereas increasing the
      rate of capping or the membrane resistance reduces cell speed. We consider
      several variants of nucleation (spontaneous, tip, and side branching) and find
      best agreement with experimentally measured spatial profiles of filament and tip
      density in the side branching case.

PMID- 16600306
TI  - Campylobacter coli enteritis and Guillain-Barre syndrome: no evidence of
      molecular mimicry and serological relationship.
AB  - Campylobacter coli was isolated from two Guillain-Barre syndrome (GBS) patients
      who had anti-GM1 and anti-GD1 IgG antibodies. Although both this bacteria and
      Campylobacter jejuni are common causes of diarrheal illness, previous studies
      have focused only on C. jejuni as the causal agent of GBS. To determine whether
      C. coli also is a causative agent, we examined the hypothesis that production of
      anti-ganglioside antibodies is induced by ganglioside-mimics on that bacterial
      lipo-oligosaccharide (LOS), as in C. jejuni-associated GBS. LOSs of both C. coli
      isolates had very weak reactivities with anti-GM1 and anti-GD1a IgG monoclonal
      antibodies, whereas those of some GBS-related C. jejuni isolates had strong
      reactivities. Anti-GM1 and anti-GD1a IgG antibodies from the two patients were
      not absorbed as much by the LOSs of their isolates as were those of GBS-related
      C. jejuni strains. These findings do not support the hypothesis of ganglioside
      mimicry on C. coli isolates' LOSs. We next made a serological assay of recent C.
      coli infection in 74 patients with GBS, 26 with Fisher syndrome (FS), 49 with
      other neurological diseases (OND), and 37 normal controls (NC) using the
      bacterial outer membrane protein as antigen. Eight (11%) GBS and two (8%) FS
      patients had two or three classes of IgG, IgM, and IgA anti-C. coli antibodies.
      Anti-C. jejuni IgG and IgA antibody titers were significantly higher than those
      of anti-C. coli (respectively, p = 0.03 and 0.01). This suggests that anti-C.
      coli antibodies cross-react with C. jejuni protein. We concluded that a C. coli
      infection was not the cause of GBS in our patients. Both isolation of a
      microorganism from, and the positive infectious serology of, GBS patients do not
      always indicate the causal agent.

PMID- 16600308
TI  - Increases in transepithelial vectorial Na+ transport facilitates Na+-dependent L
      DOPA transport in renal OK cells.
AB  - The present study evaluated the hypothesis of whether increases in vectorial Na+
      transport translate into facilitation of Na+-dependent L-DOPA uptake in cultured
      renal epithelial tubular cells. Increases in vectorial Na+ transport were
      obtained in opossum kidney (OK) cells engineered to overexpress Na+-K+-ATPase
      after transfection of wild type OK cells with the rodent Na+-K+-ATPase alpha1
      subunit. The most impressive differences between wild type and transfected OK
      cells are that the latter overexpressed Na+-K+-ATPase accompanied by an increased
      activity of the transporter. Non-linear analysis of the saturation curve for l
      DOPA uptake revealed a Vmax value (in nmol mg protein/6 min) of 62 and 80 in wild
      type and transfected cells, respectively. The uptake of a non-saturating
      concentration (0.25 microM) of [14C]-L-DOPA in OK-WT cells was not affected by
      Na+ removal, whereas in OK-alpha1 cells accumulation of [14C]-L-DOPA was clearly
      dependent on the presence of extracellular Na+. When Na+ was replaced by choline,
      the inhibitory profile of neutral l-amino acids, but not of basic and acidic
      amino acids, upon [14C]-L-DOPA uptake in both cell types, was significantly
      greater than that observed in the presence of extracellular Na+. It is concluded
      that enhanced ability of OK cells overexpressing Na+-K+-ATPase to translocate Na+
      from the apical to the basal cell side correlates positively with their ability
      to accumulate L-DOPA, which is in agreement with the role of Na+ in taking up the
      precursor of renal dopamine.

PMID- 16600309
TI  - Antimetastatic activity of Sulforaphane.
AB  - The effect of Sulforaphane on the inhibition of lung metastasis induced by B16F
      10 melanoma cells was studied in C57BL/6 mice by three different modalities of
      administration-simultaneous, prophylactic and after tumour developed. Of this
      simultaneous mode of Sulforaphane administration was found to be most effective.
      There was 95.5% inhibition of lung tumour nodule formation and 94.06% increase in
      the life span of metastatic tumour bearing animals. Highly elevated levels of
      lung hydroxyproline, lung uronic acid, lung hexosamine, serum sialic acid and
      serum gamma-glutamyl transpeptidase (GGT) in the metastatic control animals was
      found to be significantly lowered in the Sulforaphane treated animals.
      Histopathological analysis of lung tissues also correlated with these results. In
      the in vitro system Sulforaphane showed a significant inhibition in the invasion
      of B16F-10 melanoma cells across the collagen matrix. (3)H-thymidine
      proliferation assay showed that Sulforaphane could inhibit the proliferation of
      B16F-10 melanoma cells in vitro. Gelatin zymographic analysis showed that
      Sulforaphane could inhibit the activation of matrix metalloproteinases. These
      findings suggest that Sulforaphane reduced the invasion of B16F-10 melanoma cells
      by the inhibition of activation of matrix metalloproteinases, thereby inhibiting
      lung metastasis.

PMID- 16600310
TI  - Antinociceptive, antiedematogenic and antiangiogenic effects of benzaldehyde
      semicarbazone.
AB  - Semicarbazones induce an anticonvulsant effect in different experimental models.
      As some anticonvulsant drugs also have anti-inflammatory activity, the effects of
      benzaldehyde semicarbazone (BS) on models of nociception, edema and angiogenesis
      were investigated. BS (10, 25 or 50 mg/kg, i.p.) markedly inhibited the second
      phase of nociceptive response induced by formaldehyde (0.34%, 20 microl) in mice,
      but only the highest dose inhibited the first phase of this response. The thermal
      hyperalgesia and mechanical allodynia induced by carrageenan (1%, 50 microl,
      i.pl.) in rats were also inhibited by BS (50 mg/kg, i.p.). However, treatment of
      mice with BS did not induce an antinociceptive effect in the hot-plate model. The
      paw edema induced by carrageenan (1%, 50 microl, i.pl.) in rats was inhibited by
      BS (25 or 50 mg/kg, i.p.). Treatment of mice with BS (0.25, 0.5 or 2.5 mg/kg/day,
      i.p., 7 days) also inhibited angiogenesis induced by subcutaneous implantation of
      a sponge disc. It is unlikely that the antinociceptive effect induced by BS
      results from motor incoordination or a muscle relaxing effect, as the mice
      treated with this drug displayed no behavioral impairment in the rotarod
      apparatus. In conclusion, we demonstrated that BS presents antinociceptive,
      antiedematogenic and antiangiogenic activities. An extensive investigation of the
      pharmacological actions of BS and its derivatives is justified and may lead to
      the development of new clinically useful drugs.

PMID- 16600311
TI  - The effects of acute corticosterone on lithium chloride-induced conditioned place
      aversion and locomotor activity in rats.
AB  - Acute administration of corticosterone (CORT) facilitates learning in a number of
      associative paradigms including lithium chloride (LiCl)-induced conditioned taste
      aversion learning. The present study examined the effects of acute CORT on LiCl
      induced conditioned place aversions in male rats. Automated open-fields were
      partitioned into two chambers distinct in tactile and visual cues. Animals
      received either LiCl (64 mg/kg, 0.15 M) or saline (NaCl, 0.15 M) followed 10 min
      later by either CORT (5 mg/kg) or beta-cyclodextrin vehicle (45%) prior to
      placement in one of the chambers. Control rats received NaCl-Vehicle paired with
      both chambers. Three experimental groups received either NaCl-CORT, LiCl-Vehicle
      or LiCl-CORT paired with the preferred chamber and NaCl-Vehicle (control) paired
      with the non-preferred chamber. During extinction trials, animals were allowed to
      choose between the two chambers. Locomotor activity and its distribution within
      the chambers were assessed during both conditioning and extinction trials. CORT
      administration produced significant increases in a variety of measures of
      locomotor activity during conditioning trials. During extinction trials both LiCl
      groups displayed a conditioned place aversion while the NaCl-CORT group did not.
      In addition, significant increases in vertical activity were recorded in both
      LiCl groups in the LiCl-paired chamber. Moreover, CORT administration had no
      effect on LiCl-induced conditioned place aversion as time spent in the LiCl
      paired chamber did not significantly differ between LiCl-Vehicle and LiCl-CORT
      groups. Significant increases in a number of measures of horizontal activity were
      also observed in both CORT groups. The present study shows that acute CORT
      administration does not significantly influence LiCl-induced conditioned place
      aversions and suggests that the facilitatory effects of acute CORT administration
      on learning are highly context-dependent.

PMID- 16600312
TI  - Hydrocarbon pollution in coastal sediments of Tierra del Fuego Islands, Patagonia
      Argentina.

PMID- 16600313
TI  - Formation of perfused, functional microvascular tubes in vitro.
AB  - This work describes the formation, perfusion, and maturation of three-dimensional
      microvascular tubes in vitro. These tubes consisted of confluent monolayers of
      human endothelial cells that lined open, cylindrical channels within collagen
      gels. Perivascular cells could be directly embedded within the gels or added
      after endothelial cells grew to confluence. The tubes spanned the entire 5-7 mm
      extent of the gels; their diameters initially ranged from 55 to 120 microm and
      increased to 75-150 microm after maturation. Endothelial tubes displayed a strong
      barrier function over 5 days, resisted adhesion of leukocytes, and reacted
      quickly to inflammatory stimuli by breakdown of the barrier and support of
      leukocyte adhesion. These tubes resembled venules and "giant" capillaries in both
      their cellular organization and function, and we believe that they will serve as
      useful in vitro models of inflammation under constant perfusion.

PMID- 16600314
TI  - Low amplitude entrainment of mice and the impact of circadian phase on behavior
      tests.
AB  - A tremendous increase in the use of genetically engineered mice as experimental
      animals has led to increased scrutiny of mouse models generally and mouse
      behavioral paradigms specifically. Although mice are nocturnal, for practical
      reasons, most experimental procedures, including behavioral studies, are
      conducted during their inactive, sleep phase. Accumulating evidence indicates
      that myriad behavioral, cellular and biochemical processes fluctuate with
      circadian rhythmicity; however, time of day at which experiments are conducted is
      rarely controlled. The impact of circadian phase on the reliability of
      experimental results has received little attention and the present data are
      conflicting. This study addressed two questions. First, will laboratory mice in a
      typical animal care facility entrain to a low amplitude light cycle using
      bright/dim rather than light/dark cycles? A positive answer will make reversing
      photocycle easy to implement in any facility as dim light suitable for animal
      husbandry and behavioral testing can substitute for darkness during work hours.
      By monitoring home cage wheel running, we examined the effectiveness of a
      dim/bright photocycle as a zeitgeiber. We found that mice subjected to dim/bright
      photocycles effectively entrained such that their subjective night and activity
      onset coincided with the beginning of the dim light period, suggesting a
      potential strategy for standardization and management of circadian phase in
      nocturnal animals. In a second experiment, we asked what effect circadian phase
      has on behavioral performance in commonly used mouse behavioral tests. We found
      no main effect of circadian phase on outcome in open field activity, elevated
      plus maze emotionality, water maze spatial memory, novel object exploration and
      hyperactivity in response to amphetamine; however, we observed occasional
      interactions between circadian phase and both strain and sex that were neither
      consistent nor systematic. These data suggest that the tests examined here are
      relatively impervious to circadian phase. In general, testing mice during their
      active phase is more suitable for behavioral studies; a reversed dim/bright
      photocycle potentially offers one practical strategy for managing rodents'
      circadian cycles.

PMID- 16600315
TI  - The effects of histaminergic agents in the ventral hippocampus of rats in the
      plus-maze test of anxiety-like behaviours.
AB  - It has been suggested that histamine have modulatory influence on anxiety-related
      behaviours both in animals and humans. Ventral hippocampus (VHC) may also be an
      important brain site in the modulation of fear or anxiety. In the present study,
      the effects of histaminergic agents on anxiety-related behaviours in the rats,
      using plus-maze test has been investigated. Intra-VHC administration of histamine
      (2.5, 5 and 7.5 microg/rat) decreased %OAT and %OAE but not locomotor activity,
      showing an anxiogenic response. Pretreatment of animals with either pyrilamine, a
      H1 receptor antagonist (10 microg/rat), or ranitidine, a H2 receptor antagonist
      (10 microg/rat) reverse anxiogenic response of histamine (2.5, 5 and 7.5
      microg/rat). However, intra-VHC microinjection of higher doses of pyrilamine (40
      microg/rat) or ranitidine (20 and 40 microg/rat) alone increased anxiety-like
      behaviours in rats. Our results showed that histamine may modulate anxiety-like
      behaviours via H1 and H2 receptors in the ventral hippocampus of the rats.

PMID- 16600316
TI  - Oil content of Arabidopsis seeds: the influence of seed anatomy, light and plant
      to-plant variation.
AB  - Arabidopsis thaliana is frequently used as a model for the study of oilseed
      biology and metabolism. However, the very small seeds of Arabidopsis can
      complicate analysis of their oil content and influence the application of results
      to larger-seeded plants. Here, we describe how seed anatomy, light, and plant-to
      plant variation influence the content and measurement of oil in Arabidopsis
      seeds. The anatomy of Arabidopsis and Brassica napus seeds were compared and the
      distribution of mass, oil and the fatty acid composition of different seed parts
      were determined. In Brassica, 90% of the seed oil resides in the cotyledons that
      contribute 74% of seed mass. By contrast, the values for Arabidopsis are 60% and
      45%, respectively, with a higher fraction of the oil deposited in the radicle,
      hypocotyl, endosperm and seed coat. Growth of Arabidopsis plants with 600
      micromol m(-2) s(-1) light resulted in a two-fold higher seed yield, a 40%
      increase in mass per seed and a 60% increase in oil per seed compared to growth
      at 100 micromol m(-2) s(-1). Factors that influence the analysis of oil content
      were evaluated. Intact-seed transmethylation followed by gas chromatography (GC)
      analysis provided reproducible analysis of Arabidopsis seed oil. However, plant
      to-plant variation in oil content is large and we analyzed how this influences
      the ability to detect statistically valid changes in oil between different
      genotypes. These observations establish a reference data set on the fatty acid
      composition and distribution of mass and oil between tissues of Arabidopsis seeds
      that should help to predict the applicability of results obtained with
      Arabidopsis to other oilseeds.

PMID- 16600317
TI  - Fur from Microcystis aeruginosa binds in vitro promoter regions of the
      microcystin biosynthesis gene cluster.
AB  - Promoter regions of the mcy operon from Microcystis aeruginosa PCC7806, which is
      responsible for microcystin synthesis in this organism, exhibit sequences that
      are similar to the sequences recognized by Fur (ferric uptake regulator). This
      DNA-binding protein is a sensor of iron availability and oxidative stress. In the
      presence of Fe(2+), a dimer of Fur binds the iron-boxes in their target genes,
      repressing their expression. When iron is absent the expression of those gene
      products is allowed. Here, we show that Fur from M. aeruginosa binds in vitro
      promoter regions of several mcy genes, which suggests that Fur might regulate,
      among other factors, microcystin synthesis. The binding affinity is increased by
      the presence of metal and DTT, suggesting a response to iron availability and
      redox status of the cell.

PMID- 16600318
TI  - Trend in incidence of hepatitis B virus infection during a decade of universal
      childhood hepatitis B vaccination in Saudi Arabia.
AB  - Since 1990, the national strategy to eliminate hepatitis B virus (HBV) infection
      in Saudi Arabia has included universal administration of HBV vaccine to all
      infants. From 1990 to 1995 this vaccine was also routinely administered to
      children at school entry. The prevalence of hepatitis B surface antigen (HBsAg)
      among children before this programme was reported to be 6.7%. The objective of
      this study was to describe the trend in incidence of HBV infection over a decade
      of surveillance following the introduction of this programme. From January 1990
      to December 1999 a total of 30,784 cases of HBV infection (positive for HBsAg)
      were reported. The total number of HBV infections among children <15 years of age
      was 4180 cases, with a prevalence of 0.05%. The total number of HBV infections
      among adults was 26,604 cases, with a prevalence of 0.22%. The prevalence varied
      by region, ranging from 0.03% to 0.72% with a mean prevalence of 0.15%. There was
      a clear decline in incidence among children whereas the incidence in adults
      slightly rose, perhaps owing to population growth estimated to be 3.3% annually.
      This study showed that the universal childhood HBV vaccination programme had an
      enormous positive impact on HBsAg seroprevalence among children in Saudi Arabia.

PMID- 16600319
TI  - Metabolic transformation of methylseleninic acid through key selenium
      intermediate selenide.
AB  - Methylseleninic acid (MSA(IV)) [CH(3)Se(O)OH] is readily reducible to
      methylselenol [CH(3)SeH], the assumed lyase metabolite and the proposed
      biologically active form of methylated selenoamino acids. At the same time,
      MSA(IV) is an oxidation product of the major urinary metabolite selenosugar.
      (77)Se-Enriched MSA(IV) was injected intravenously into rats (25 microg Se/kg
      body weight), and urine, blood and liver were obtained at five time points after
      the injection. Time-related changes in the concentration of (77)Se were
      determined together with speciation analysis of the labeled metabolites. (77)Se
      was mostly moved into red blood cells (RBCs) within 10 min, and then
      redistributed into organs within 30 min. Excessive (77)Se taken up by the liver
      was first detected as selenosugar A and then as B, suggesting that MSA(IV) was
      transformed to selenide, and then to selenosugar A followed by methylation to
      selenosugar B (urinary metabolite). (77)Se was incorporated also into
      selenoproteins (most efficiently to plasma selenoprotein P that is synthesized in
      liver), suggesting that MSA(IV) is utilized for the synthesis of selenosugar (for
      excretion) and selenoproteins (for utilization) through selenide. In vitro
      experiments with simultaneous incubation of (77)Se-MSA(IV) and (82)Se-selenite in
      a RBC suspension revealed the precise difference in the metabolism between
      MSA(IV) and selenite in RBCs. (77)Se excreted into the urine was mostly detected
      as selenosugar but with a distinct amount of trimethylselenonium, suggesting that
      selenosugar and trimethylselenonium are produced depending on the capacity to
      transform methylselenol to selenide. MSA(IV) was suggested to be reduced to
      methylselenol (allowing the production of a proposed active form of selenium),
      and then transformed (demethylated) to selenide for utilization and excretion.

PMID- 16600320
TI  - Cross-reactive CTL recognizing two HLA-A*02-restricted epitopes within the BK
      virus and JC virus VP1 polypeptides are frequent in immunocompetent individuals.
AB  - Two HLA-A*02-restricted epitopes have been identified within the VP1 polypeptide
      of a human polyomavirus, BK virus, which is associated with polyomavirus
      associated nephropathy in kidney transplant patients. Immunization of transgenic
      mice with recombinant modified vaccinia Ankara expressing BKV VP1 (rMVA-BKV VP1)
      elicited functional CTL populations recognizing the sequences LLMWEAVTV (amino
      acids residues 108-116, BKV VP1p108) and AITEVECFL (residues 44-52, BKV VP1p44)
      and cross-reactive to the previously described JC virus VP1 homologs. Flow-based
      analyses of PBMC from a panel of thirty healthy HLA-A*02 human volunteers
      indicated that the majority of these subjects harbored functional CTL populations
      recognizing the BKV epitopes and cross-reactive with the JCV homologs. CTL
      recognizing the JCV VP1p100 and JCV VP1p36 epitopes have previously been
      associated with prolonged survival in progressive multifocal leukoencephalopathy
      patients. These findings suggest that infection with BKV or JCV could potentially
      induce cross-protective T-cell immunity against diseases associated with these
      viruses.

PMID- 16600321
TI  - Effect of signal intensity on perceived speed.
AB  - The effect of signal intensity (proportion of dots moving in the same direction
      compared to noise dots that move in random directions) on perceived speed was
      investigated. It was found that increasing signal level decreased the perceived
      speed of the stimulus. This finding indicates that global-motion pooling
      processes play a role in the extraction of speed information. It is suggested
      that the amount of relative motion in the stimulus influences perceived speed,
      with perceived speed increasing with increasing relative motion. The results are
      discussed in relation to the notion that speed and direction are processed, at
      least in part, differently.

PMID- 16600322
TI  - Contribution of lateral interactions in V1 to organization of response
      properties.
AB  - We propose a model of self-organization of synaptic connections in V1,
      emphasizing lateral interactions. Subject to Hebbian learning with decay,
      evolution of synaptic strengths proceeds to a stable state in which all synapses
      are either saturated, or have minimum pre/post-synaptic coincidence. The most
      stable configuration gives rise to anatomically realistic "local maps", each of
      macro-columnar size, and each organized as Mobius projections of retinotopic
      space. A tiling of V1, constructed of approximately mirror-image reflections of
      each local map by its neighbors is formed, accounting for orientation-preference
      singularities, linear zones, and saddle points-with each map linked by
      connections between sites of common orientation preference. Ocular dominance
      columns are partly explained as a special case of the same process. The
      occurrence of direction preference fractures always in odd numbers around
      singularities is a specific feature explained by the Mobius configuration of the
      local map. Effects of stimulus velocity, orientation relative to direction of
      motion, and extension, upon orientation preference, which are not accounted for
      by spatial filtering, are explained by interactions between the classic receptive
      field and global V1.

PMID- 16600323
TI  - Vertical-size disparities are temporally integrated for slant perception.
AB  - We investigated temporal properties of vertical-size and horizontal-size
      disparity processing for slant perception. Subjects indicated perceived slants
      for a stereoscopic stimulus in which the two magnitudes of vertical-size or
      horizontal-size disparities were oscillated stepwise with various frequencies
      (from 0.2 to 10 Hz). For the stimulus with vertical-size disparity oscillation,
      two slants corresponding to the two magnitudes of disparity were perceived for
      low-frequency conditions, whereas only a static mean slant of the two slants was
      perceived for high frequencies (5 and 10 Hz). For the stimulus with horizontal
      size disparity oscillation, two slants were perceived for all the temporal
      frequency conditions. These results indicate that temporal properties of vertical
      and horizontal-size disparity processing are clearly different and vertical-size
      disparities are temporally integrated over a period of around 500 ms for slant
      perception.

PMID- 16600324
TI  - Biodegradation of nitrilotriacetic acid (NTA) and ferric-NTA complex by aerobic
      microbial granules.
AB  - Development of mixed-culture microbial granules under aerobic conditions in a
      sequencing batch reactor (SBR), capable of completely degrading a recalcitrant
      metal chelating agent is reported. In laboratory-scale reactor studies, the
      microbial granules degraded 2mM of free nitrilotriacetic acid (NTA) and Fe(III)
      NTA completely in 14 and 40 h, respectively. Free NTA was degraded at a specific
      rate of 0.7 mM (gMLSS)(-1)h(-1), while Fe(III)-NTA was degraded at a specific
      rate of 0.37 mM (gMLSS)(-1)h(-1). Achievement of significant degradation rates of
      NTA and ferric-NTA in double-distilled water suggests that the microbial
      metabolism is not constrained by lack of essential elements. Efficient
      degradation of recalcitrant synthetic chelating agents by aerobic microbial
      granules suggests their potential application in a variety of situations where
      heavy metals or radionuclides are to be co-disposed with metal chelating agents.

PMID- 16600325
TI  - Actinomycetes in relation to taste and odour in drinking water: myths, tenets and
      truths.
AB  - Actinomycetes are a complex group of bacteria present in a wide variety of
      environments, either as dormant spores or actively growing. Some actinomycetes
      produce two potent terpenoids (geosmin and 2-methylisoborneol (MIB)) and
      pyrazines, common causes of drinking water off flavours, and have been implicated
      in taste and odour episodes. However, isolation from a water source is not
      evidence that actinomycetes caused a taste and odour event. Dormant spores of
      actinomycetes may be isolated from aquatic environments in high concentrations,
      despite production in the terrestrial environment. Similarly, odourous compounds
      produced by actinomycetes may be produced terrestrially and washed into aquatic
      environments, with or without the actinomycetes that produced them. Actinomycetes
      may exist as actively growing mycelium in small, specialized habitats within an
      aquatic system, but their odourous compounds may influence a wider area. This
      paper attempts to elucidate the types and activities of actinomycetes that may be
      found in, or interact with, drinking water supplies.

PMID- 16600326
TI  - Optimisation of hydraulic performance to maximise faecal coliform removal in
      maturation ponds.
AB  - The present study was conducted with the aim of improving faecal coliform (FC)
      and faecal streptococcus (FS) removal efficiencies in tertiary maturation stages
      of a sewage treatment plant in Southern England, where climatic conditions are
      sub-optimal. The research used intensive field assessments (bacteriological,
      general quality and hydraulic) to identify the parameters that affect the
      bacteriological quality of the effluent from three parallel maturation ponds
      (North, Central and South) of similar geometry and dimensions. An engineering
      intervention was carried out to convert the South pond to three channels to
      increase the L/W ratio from 9:1 to 79:1. Hydraulic tracer studies in the South
      pond with Rhodamine WT showed that the dispersion number 'd' was reduced from
      0.37 (dispersed flow) to 0.074 by this intervention under similar flow conditions
      (4.5l/s). Hydraulic retention time was thus increased by 5h, delay in jet flow
      short-circuiting was increased from 2.5 to 17.5h thus increasing the exposure
      times for all elements. As a result of the intervention FC removal increased
      substantially. Maximum channel-lagoon efficiency of 99.84% was obtained at 4.5l/s
      and 19 degrees C, when exposure to sunlight was 17 h in summer. It is concluded
      that the channel configuration produces a higher hydraulic efficiency than
      conventional maturation ponds. It is therefore recommended as a viable
      engineering solution which permits a low-cost upgrading of plant performance,
      requiring no additional land, and with minimal maintenance costs.

PMID- 16600327
TI  - Geochemical variations in aeolian mineral particles from the Sahara-Sahel Dust
      Corridor.
AB  - The Sahara-Sahel Dust Corridor runs from Chad to Mauritania and expels huge
      amounts of mineral aerosols into the Atlantic Ocean. Data on samples collected
      from Algeria, Chad, Niger, and Western Sahara illustrate how corridor dust
      mineralogy and chemistry relate to geological source and weathering/transport
      history. Dusts sourced directly from igneous and metamorphic massifs are
      geochemically immature, retaining soluble cations (e.g., K, Na, Rb, Sr) and
      accessory minerals containing HFSE (e.g., Zr, Hf, U, Th) and REE. In contrast,
      silicate dust chemistry in desert basins (e.g., Bodele Depression) is influenced
      by a longer history of transport, physical winnowing (e.g., loss of Zr, Hf, Th),
      chemical leaching (e.g., loss of Na, K, Rb), and mixing with intrabasinal
      materials such as diatoms and evaporitic salts. Mineral aerosols blown along the
      corridor by the winter Harmattan winds mix these basinal and basement materials.
      Dusts blown into the corridor from sub-Saharan Africa during the summer monsoon
      source from deeply chemically weathered terrains and are therefore likely to be
      more kaolinitic and stripped of mobile elements (e.g., Na, K, Mg, Ca, LILE), but
      retain immobile and resistant elements (e.g., Zr, Hf, REE). Finally, dusts blown
      southwestwards into the corridor from along the Atlantic Coastal Basin will be
      enriched in carbonate from Mesozoic-Cenozoic marine limestones, depleted in Th,
      Nb, and Ta, and locally contaminated by uranium-bearing phosphate deposits.

PMID- 16600328
TI  - Fe-exchanged zeolite as the effective heterogeneous Fenton-type catalyst for the
      organic pollutant minimization: UV irradiation assistance.
AB  - The issue of investigations in this study was an application of heterogeneous
      Fenton-type catalyst, Fe-exchanged zeolite FeZSM5, for the minimization of phenol
      and overall organic content in the model wastewater. Applied treatment systems
      included variation of heterogeneous and homogeneous Fenton-type catalyst with and
      without the assistance of UV irradiation, FeZSM5/H2O2, Fe2+/H2O2/NH4ZSM5,
      Fe3+/H2O2/NH4ZSM5, UV/FeZSM5/H2O2, UV/Fe2+/H2O2/NH4ZSM5 and UV/Fe3+/H2O2/NH4ZSM5.
      Processes efficiency was evaluated on the basis of phenol removal, mineralization
      extent, H2O2 consumption and concentration of iron ions in the bulk after the
      treatment. By all applied systems, complete phenol removal was achieved in less
      than 30 min of treatment time. Systems including heterogeneous Fenton-type
      catalyst showed somewhat lower mineralization efficiency in comparison to the
      corresponding systems applying homogeneous Fenton-type catalysts and the addition
      of synthetic zeolite NH4ZSM5. Significantly lower concentration of iron ions in
      the bulk after the treatment could give these systems, particularly
      UV/FeZSM5/H2O2, a great advantage over the homogeneous Fenton-type systems.

PMID- 16600329
TI  - Mercury contamination in fish from gold mining areas in Indonesia and human
      health risk assessment.
AB  - This study investigates the effects on fish and assesses human health hazards
      from mercury released in two gold mining areas in Indonesia: Tatelu (North
      Sulawesi Province) and Galangan (Katingan District, Central Kalimatan Province).
      In Tatelu, 154 fish specimens of 10 freshwater species were collected, as well as
      five marine species from the fish market. The mean concentration of total mercury
      in muscles of freshwater fish from this area was 0.58+/-0.44 microg/g, with more
      than 45% of fish having Hg levels above the WHO guideline for human consumption
      of 0.5 microg/g. In Galangan, where 263 fish specimens of 25 species were
      collected, the total mercury in muscles averaged 0.25+/-0.69 microg/g. Excluding
      data from flooded open pits in sub-area P4, mean Hg levels in fish from Galangan
      were 2 to 4 times lower than 0.5 microg/g, while fewer than 10% of fish from
      Galangan exceeded WHO guidelines. The Hazard Quotient (HQ) was applied to both
      areas to determine the threat of MeHg exposure for communities in both areas. The
      HQ is a risk assessment indicator which defines the ratio of exposure level to a
      single substance in relation to a reference dose. Samples from Tatelu (excluding
      marine species) had an HQ above one, while those from Galangan resulted in values
      of 2.4 for the whole area and 9.9 for sub-area P4, pointing to potentially
      harmful fish consumption for the local population. By using the single
      compartment model to estimate mercury levels in blood and hair from daily intake
      dose, sub-area P4 showed the highest levels, higher than the upper limit
      guideline for pregnant women, but still lower than threshold levels associated
      with observed clinical effects.

PMID- 16600330
TI  - Trace element availability and plant growth in a mine-spill-contaminated soil
      under assisted natural remediation II. Plants.
AB  - In this second part, we evaluated the effects of different amendments on plant
      growth (Agrostis stolonifera L.), and trace element accumulation and removal by
      plants in a trace element (As, Cd, Cu, Pb and Zn) contaminated soil. Description
      of the various treatments is given in Part I of this work. The plants were grown
      for consecutive periods (2002, 2003, 2004), 5 months each and harvested twice in
      each period. Results showed that plant growth was enhanced and trace element
      concentrations in plant were reduced in SL, MWC, BC and LEO treatments in the
      first period. No significant differences were observed in subsequent periods.
      This seemed to be related with changes in soil pH. Removal of trace elements was
      higher in SL, MWC, BC and LEO treatments due to higher biomass production in the
      first period. In following years no significant differences between treatments
      were found. Data from Part I of this study were also used to compare trace
      element bioavailable concentrations extracted with 0.01 M CaCl2 and 0.05 M EDTA
      with trace elements in plant. We observed that 0.01 M CaCl2 was more suitable for
      determination of bioavailable concentrations and that extraction with EDTA
      overestimated biovailability of trace elements in amended treatments, especially
      in those where composts were added.

PMID- 16600331
TI  - Simulation of future stream alkalinity under changing deposition and climate
      scenarios.
AB  - Models of soil and stream water acidification have typically been applied under
      scenarios of changing acidic deposition, however, climate change is usually
      ignored. Soil air CO2 concentrations have potential to increase as climate warms
      and becomes wetter, thus affecting soil and stream water chemistry by initially
      increasing stream alkalinity at the expense of reducing base saturation levels on
      soil exchange sites. We simulate this change by applying a series of physically
      based coupled models capable of predicting soil air CO2 and stream water
      chemistry. We predict daily stream water alkalinity for a small catchment in the
      Virginia Blue Ridge for 60 years into the future given stochastically generated
      daily climate values. This is done for nine different combinations of climate and
      deposition. The scenarios for both climate and deposition include a static
      scenario, a scenario of gradual change, and a scenario of abrupt change. We find
      that stream water alkalinity continues to decline for all scenarios (average
      decrease of 14.4 microeq L-1) except where climate is gradually warming and
      becoming more moist (average increase of 13 microeq L-1). In all other scenarios,
      base cation removal from catchment soils is responsible for limited alkalinity
      increase resulting from climate change. This has implications given the extent
      that acidification models are used to establish policy and legislation concerning
      deposition and emissions.

PMID- 16600332
TI  - Effect of different organotins on DNA of mollusk (Scapharca inaequivalvis)
      erythrocytes assessed by the comet assay.
AB  - The alkaline comet assay, employing a single-cell gel-electrophoresis, is a
      rapid, simple and sensitive technique for visualizing and measuring DNA damage
      leading to strand breakage in individual cells. In this study, we report data
      about the effect of different organotin compounds (MBTC, DBTC and TBTC) on DNA
      from erythrocytes of the Scapharca inaequivalvis bivalve mollusc. Our results
      show significant DNA damage after 30 min in vitro incubation with 10microM of
      organotins. Since TBTC turned out to be the most genotoxic compound, followed by
      MBTC and DBTC, we exposed the molluscs to 50ppb of TBTC for 11 days. A
      significant increase of comet parameters was measured in our experimental
      conditions. The use of the comet test as a high-throughput screening assay to
      monitor the effect of environmental pollutants on marine organisms has been
      proposed.

PMID- 16600333
TI  - Effect of scale of Cd heterogeneity and timing of exposure on the Cd uptake and
      shoot biomass, of plants with a contrasting root morphology.
AB  - A pot experiment was conducted to investigate the influence of spatial
      heterogeneity of Cd distribution in soil on shoot biomass, shoot metal
      concentration and total shoot Cd uptake by lettuce (Lactuca sativa, variety Tom
      Thumb) and Indian mustard (Brassica juncea). Five different soil treatments had
      similar overall concentration of Cd per pot, but different scales of
      heterogeneity and also timing of plant exposure during the growth cycle. The
      presence and scale of heterogeneity and timing of exposure were found to have
      significant effects on shoot biomass for both plants (with one exception). The
      mean values of Cd mass taken up were significantly affected by the presence of
      heterogeneity and timing only for lettuce. Only the scale of heterogeneity
      affected the uptake of Cd by Indian mustard, presumably because of its larger
      root system (approximately 18 cm, compared with approximately 5 cm for lettuce).
      These findings have important implications for phytoremediation, and for human
      health risk assessment where leafy vegetables are grown in situations with highly
      elevated Cd concentrations.

PMID- 16600334
TI  - Mercury in the topsoil and dust of Beijing City.
AB  - Research on mercury concentration in the dust and topsoil of Beijing City reveals
      the following conclusions: mercury concentration in Beijing topsoil and dust is
      middle compared to other mercury concentration studies and varies greatly in
      different sampling spots. Mercury concentration in the topsoil is between
      0.019mg.kg(-1) and 0.966mg.kg(-1), it is about 2.11 times and 12.08 times of
      mercury concentration background in Beijing soil respectively. Mercury
      concentration in Beijing dust has a range of 0.053 to 1.378mg.kg(-1); the maximum
      mercury concentration in the Beijing dust in 2003 is about 2.2 times of that in
      1992. These results show that mercury pollution in Beijing topsoil and dust are
      serious, and mercury tends to enrich in the dust compared to the adjacent
      topsoil. Mercury in topsoil and dust of Beijing City has obvious regional
      differentiation characteristics, which is highest in the center of Beijing City
      and lower away from the center to the suburbs. In detail, mercury concentration
      in the topsoil samples and dust samples are highest in Dongsi area and lowest in
      the blank spot. Mercury in Beijing's topsoil belonging to point pollution is
      mainly from local area; mercury in the dust belongs to non-point source pollution
      because the source of mercury in the dust is very complex. Natural factors and
      anthropological factors have certain effect on mercury concentration in the
      topsoil and dust, and anthropological factors have more effect. The results are
      very important to protect and enhance our environmental quality.

PMID- 16600335
TI  - Total and organic Hg concentrations in cephalopods from the North Eastern
      Atlantic waters: influence of geographical origin and feeding ecology.
AB  - Total (T-Hg) and organic (O-Hg) mercury concentrations and tissue distribution
      were examined in 20 species of cephalopods (n=278) from the north eastern
      Atlantic waters, i.e. from the Bay of Biscay to the Faroe Islands. Concentrations
      of T-Hg in whole cephalopods showed elevated variations among species, i.e. from
      40 to 3560ng g(-1) dwt, but a low variability within each species (mean CV%=39%).
      With the exception of oceanic squids, the digestive gland globally displayed
      higher T-Hg concentrations than the remaining tissues. In contrast, O-Hg
      concentrations determined in selected species were generally higher in the
      remaining tissues. Despite higher T-Hg concentrations, the digestive gland weakly
      contributed to the total body burden of both T-Hg and O-Hg (<25% and <15%,
      respectively). In fact, from 75% to 95% of the T-Hg and O-Hg were contained in
      the muscular remaining tissues. Therefore, O-Hg may have a strong affinity to
      proteins in cephalopods. Sex and size only significantly influenced the
      bioaccumulation of Hg for the Loliginidae family. T-Hg and O-Hg concentrations
      were also influenced by geographical origin: Celtic Sea>Bay of Biscay>Faroe
      Islands, corresponding to the seawater Hg concentrations in these areas. In the
      Faroe Islands and the Celtic Sea, benthic cephalopods contained significant
      higher Hg concentrations compared to pelagic ones. This suggests that diet is not
      the main pathway of Hg uptake in cephalopods as pelagic species were expected to
      be more exposed to O-Hg through fish consumption than benthic ones.

PMID- 16600336
TI  - An application of the GLUE methodology for estimating the parameters of the INCA
      N model.
AB  - The conceptual and parameter uncertainty of the semi-distributed INCA-N
      (Integrated Nutrients in Catchments-Nitrogen) model was studied using the GLUE
      (Generalized Likelihood Uncertainty Estimation) methodology combined with
      quantitative experimental knowledge, the concept known as 'soft data'. Cumulative
      inorganic N leaching, annual plant N uptake and annual mineralization proved to
      be useful soft data to constrain the parameter space. The INCA-N model was able
      to simulate the seasonal and inter-annual variations in the stream-water nitrate
      concentrations, although the lowest concentrations during the growing season were
      not reproduced. This suggested that there were some retention processes or losses
      either in peatland/wetland areas or in the river which were not included in the
      INCA-N model. The results of the study suggested that soft data was a way to
      reduce parameter equifinality, and that the calibration and testing of
      distributed hydrological and nutrient leaching models should be based both on
      runoff and/or nutrient concentration data and the qualitative knowledge of
      experimentalist.

PMID- 16600337
TI  - Accumulation of Pb, Cu, and Zn in native plants growing on a contaminated Florida
      site.
AB  - Contamination of heavy metals represents one of the most pressing threats to
      water and soil resources as well as human health. Phytoremediation can be
      potentially used to remediate metal-contaminated sites. This study evaluated the
      potential of 36plants (17species) growing on a contaminated site in North
      Florida. Plants and the associated soil samples were collected and analyzed for
      total metal concentrations. While total soil Pb, Cu, and Zn concentrations varied
      from 90 to 4100, 20 to 990, and 195 to 2200mg kg(-1), those in the plants ranged
      from 2.0 to 1183, 6.0 to 460, and 17 to 598mg kg(-1), respectively. None of the
      plants were suitable for phytoextraction because no hyperaccumulator was
      identified. However, plants with a high bioconcentration factor (BCF, metal
      concentration ratio of plant roots to soil) and low translocation factor (TF,
      metal concentration ratio of plant shoots to roots) have the potential for
      phytostabilization. Among the plants, Phyla nodiflora was the most efficient in
      accumulating Cu and Zn in its shoots (TF=12 and 6.3) while Gentiana pennelliana
      was most suitable for phytostabilization of sites contaminated with Pb, Cu and Zn
      (BCF=11, 22 and 2.6). Plant uptake of the three metals was highly correlated,
      whereas translocation of Pb was negatively correlated with Cu and Zn though
      translocation of Cu and Zn were correlated. Our study showed that native plant
      species growing on contaminated sites may have the potential for
      phytoremediation.

PMID- 16600338
TI  - Drain blocking: an effective treatment for reducing dissolved organic carbon loss
      and water discolouration in a drained peatland.
AB  - Peatlands are an important terrestrial carbon store. However, heightened levels
      of degradation in response to environmental change have resulted in an increased
      loss of dissolved organic carbon (DOC) and an associated rise in the level of
      discolouration in catchment waters. A significant threat to peatland
      sustainability has been the installation of artificial drainage ditches. However,
      recent restoration schemes have pursued drain blocking as a possible strategy for
      reducing degradation, fluvial carbon loss and water discolouration. This paper
      investigates the effect of open cut drainage and the impact of drain blocking on
      DOC and colour dynamics in blanket peat soil-water solutions. Three treatments
      (intact peat, drained peat and drain-blocked peat) were monitored in an upland
      blanket peat catchment in the UK. DOC and colour values were significantly higher
      on the drained slopes compared with those of the intact peat, which in turn had
      greater DOC and colour values than the drain-blocked slopes. Consequently, drain
      blocking is shown to be a highly successful technique in reducing both the DOC
      concentration and level of discolouration in soil waters, even to values lower
      than those observed for the intact site, which suggests a process of store
      exhaustion and flushing may operate. The colour per carbon unit (C/C) ratio was
      significantly higher at the drain-blocked site than either the intact or the
      drained treatments, while the E4/E6 ratio (fulvic acid/humic acid) was
      significantly lower at the blocked site compared to the two other treatments. The
      high C/C and low E4/E6 ratios indicate that drain blocking also modifies the
      composition of DOC, such that darker-coloured humic substances become more
      dominant compared to the intact site. This implies disturbance to DOC production
      and/or transportation processes operating within the peat.

PMID- 16600339
TI  - The interaction of UVA and UVB wavebands with particular emphasis on signalling.
AB  - The molecular response mechanisms and signalling pathways activated upon exposure
      to ultraviolet (UV) radiation have been extensively studied within the last two
      decades. Although many signalling pathways can be activated by both UVA as well
      as UVB, there are several distinctions indicating wavelength-specific response
      patterns accommodated by the terms UVA response and UVB response. Given that
      human skin is primarily exposed to UV light from solar radiation consisting of
      both UVA and UVB, we sought to explore a potential interaction between the
      distinct UVA and UVB responses at the level of MAPK. Our results indicate that
      the two distinct stress responses elicited by UVA or UVB interact with each
      other, producing a "third" response that is different from either alone and
      cannot be explained by a simple addition of effects.

PMID- 16600340
TI  - Acute effects of UVR on human eyes and skin.
AB  - Solar UVR ( approximately 295-400 nm) has acute clinical effects on the eyes and
      the skin. The only effect on the eye is inflammation of the cornea
      (photokeratitis), which is caused by UVB (and non-solar UVC) and resolves without
      long-term consequences within 48 h. The effects on the skin are more extensive
      and include sunburn (inflammation), tanning and immunosuppression for which UVB
      is mainly responsible. Tanning is modestly photoprotective against further acute
      UVR damage. Skin colour is also transiently changed by UVA-dependent immediate
      pigment darkening, the function of which is unknown. Skin type determines
      sensitivity to the acute and chronic effects of UVR on the skin. Some of the
      photochemical events that initiate acute effects are also related to skin cancer.
      Solar UVB is also responsible for the synthesis of vitamin D.

PMID- 16600341
TI  - Vitamin D and disease prevention with special reference to cardiovascular
      disease.
AB  - Circulating 25-hydroxyvitamin D [25(OH)D] is the hallmark for determining vitamin
      D status. Serum parathyroid hormone [PTH] increases progressively when 25(OH)D
      falls below 75 nmol/l. Concentrations of 25(OH)D below 50 nmol/l or even below 25
      nmol/l are frequently observed in various population groups throughout the world.
      This paper highlights the relationship of vitamin D insufficiency with
      cardiovascular disease and non-insulin dependent diabetes mellitus, two diseases
      that account for up to 50% of all deaths in western countries. There is evidence
      from patients with end-stage renal disease that high PTH concentrations are
      causally related to cardiovascular morbidity and mortality. Activated vitamin D
      is able to increase survival in this patient group significantly. Moreover,
      already slightly enhanced PTH concentrations are associated with ventricular
      hypertrophy and coronary heart disease in the general population. Experimental
      studies have demonstrated that a lack of vitamin D action leads to hypertension
      in mice. Some intervention trials have also shown that vitamin D can reduce blood
      pressure in hypertensive patients. In young and elderly adults, serum 25(OH)D is
      inversely correlated with blood glucose concentrations and insulin resistance.
      Sun-deprived lifestyle, resulting in low cutaneous vitamin D synthesis, is the
      major factor for an insufficient vitamin D status. Unfortunately, vitamin D
      content of most foods is negligible. Moreover, fortified foods and over-the
      counter supplements usually contain inadequate amounts of vitamin D to increase
      serum 25(OH)D to 75 nmol/l. As a consequence, legislation has to be changed to
      allow higher amounts of vitamin D in fortified foods and supplements.

PMID- 16600342
TI  - Hepatocyte growth factor has protective effects on crystal-cell interaction and
      crystal deposits.
AB  - OBJECTIVES: To investigate whether hepatocyte growth factor (HGF) has a
      protective role against crystal-cell interaction and crystal deposits in a stone
      forming rat model kidney. Crystal-cell interaction is an important step during
      the early stages of stone formation. High oxalate levels induce cell injuries and
      increase adhesion of calcium oxalate monohydrate (COM) crystals to renal tubular
      cells. HGF was initially identified as the most potent growth factor for
      hepatocytes and is well known as a mesenchyme-derived pleiotropic factor for
      various types of cells. HGF has mitogenic, morphogenic, and anti-apoptotic
      effects on renal tubular cells. METHODS: Madin-Darby canine kidney cells were
      exposed to potassium oxalate or COM crystals in the presence or absence of HGF.
      We measured lactate dehydrogenase activity in the medium and analyzed apoptosis
      by FACScan. COM crystal formation was induced by administration of 0.5% ethylene
      glycol in the drinking water and forced feeding of 0.5 microg of 1alpha-OH-D3
      every other day to male Sprague-Dawley rats. Plasmid vector encoding HGF was
      transferred to stone-forming rats on day 1, and the kidneys were excised on day
      8. RESULTS: Exposure of Madin-Darby canine kidney cells to both potassium oxalate
      (KOX) and COM crystals resulted in an increase in lactate dehydrogenase release
      and the proportion of apoptotic cells, but these effects were reduced by HGF. HGF
      had inhibitory activity against the adhesion of COM crystals to Madin-Darby
      canine kidney cells. HGF gene transfer significantly reduced crystal deposits on
      the renal tubules in stone-forming rats. CONCLUSIONS: These findings suggest that
      HGF might play an important role in stone formation.

PMID- 16600343
TI  - Renal cell carcinoma presenting as a perineal mass: case report and review of the
      literature.
AB  - Perineal involvement in renal cell carcinoma (RCC) has not been reported. Vaginal
      metastases of RCC are also rare. We present a case of metastatic RCC, initially
      presenting as a perineal cyst. A 53-year-old woman presented with a perineal
      cyst, which was excised and diagnosed as clear cell carcinoma. A workup further
      revealed a vaginal mass and a renal tumor. A nephrectomy and local vaginal
      excision were performed, leading to the diagnosis of metastatic RCC. This case
      illustrates the variability in RCC presentation. Also, because vaginal clear cell
      carcinoma is rare, all such lesions should be considered potentially renal in
      origin.

PMID- 16600344
TI  - Controversies related to epithelioid variant of renal angiomyolipoma: a review of
      the literature.
AB  - We performed a review of the epithelioid-type angiomas to determine their
      clinical course and propose an appropriate plan for follow-up. We present the
      case of a patient with possible adrenal carcinoma suggested by computed
      tomography for whom the histopathologic study revealed an epithelioid
      angiomyolipoma arising from the kidney. In the absence of consensus, we consider
      it worthwhile to register the very few cases diagnosed and record a detailed
      follow-up of the clinical course. We recommend surgical treatment and a follow-up
      regimen similar to that for renal carcinoma.

PMID- 16600345
TI  - Pheochromocytoma multisystem crisis.
AB  - Pheochromocytomas can present with profound, life-threatening conditions, such as
      hypertension, fever, and rarely with a host of clinical conditions producing a
      multisystem crisis. We report a case of this syndrome and comment on clinical
      management.

PMID- 16600346
TI  - Cutaneous metastases from transitional cell carcinoma of the bladder.
AB  - Cutaneous metastases from primary genitourinary malignancies are rare and usually
      represent a poor prognostic sign. Very few cases of skin metastases from
      urothelial carcinoma have been reported in the past, and most of them were
      treated with chemotherapy. We report a patient with transitional cell carcinoma
      of the bladder who developed skin metastases after cystectomy. The lesions did
      not respond to systemic chemotherapy but resolved with local radiation therapy.
      We discuss the need to have a high index of suspicion to identify these lesions
      and the treatment approaches.

PMID- 16600347
TI  - Recurrent transitional cell carcinoma in a scrotal abscess.
AB  - We discuss a case of recurrent transitional cell carcinoma to the scrotum 5 years
      after cystectomy, along with its postoperative management and implications.

PMID- 16600348
TI  - Nested variant of urothelial carcinoma: a rare presentation.
AB  - We report a rare presentation of a nested variant of urothelial carcinoma with
      liver and bone metastases in a 74-year-old man admitted to the hospital with
      bilateral hydronephrosis and acute renal failure. At cystoscopy, both ureters
      were obstructed, with the right ureter narrowed along its entire length.
      Subsequent histopathologic examination from the ureteral resection revealed
      nested variant of urothelial carcinoma. Bilateral stents were placed, and the
      patient survived 12 months with a good partial response to chemotherapy. A total
      of 76 cases of nested variant of urothelial carcinoma have been reported
      worldwide. Our patient was the first, to our knowledge, to present with bilateral
      hydronephrosis and tumor extension along one ureter.

PMID- 16600349
TI  - Botryoid Wilms' tumor of the renal pelvis extending into the bladder.
AB  - We report a case of botryoid Wilms' tumor that occupied the renal pelvis and
      extended into the bladder. A 3-year-old boy was referred to us with a chief
      complaint of gross hematuria and micturition pain. Computed tomography showed
      tumor occupying the right renal pelvis and ureter and extending into the bladder.
      Right radical nephroureterectomy was performed. The resected specimen showed a
      botryoid sarcoma-like appearance, occupied the right renal pelvis and ureter, and
      protruded into the bladder. Histologic findings showed typical triphasic Wilms'
      tumor. Botryoid Wilms' tumor has been reported in only 16 cases in the literature
      and in only 3 cases extended into the bladder.

PMID- 16600350
TI  - Successful therapy of a malignant phyllodes tumor of the prostate after
      postoperative local failure.
AB  - A 19-year-old student who had presented with acute urinary retention was referred
      to our hospital with biopsy diagnosis of proliferating mesenchymal tumor of the
      prostate. Magnetic resonance imaging showed enlarged prostatic masses. Suspecting
      prostate sarcoma, we performed a nerve-sparing radical prostatectomy. Histologic
      diagnosis of the tumor was prostatic malignant phyllodes tumor. Five months after
      the operation, bilateral obturator lymph node metastases appeared, which were
      treated with etoposide, ifosfamide, and cisplatin chemotherapy. After a good
      response was achieved with four cycles of the chemotherapy, pelvic irradiation
      was added. Since then, there has been no evidence of recurrence for more than 4
      years.

PMID- 16600351
TI  - Cystic recurrence of prostate cancer.

PMID- 16600352
TI  - A meta-analysis of the performance characteristics of the free prostate-specific
      antigen test.
AB  - OBJECTIVES: To conduct a meta-analysis of the diagnostic performance of the
      percent free prostate-specific antigen (%fPSA) test in determining prostate
      cancer status and to assess its value in helping to decide whether to biopsy the
      prostate. METHODS: Articles identified through a MEDLINE search were included if
      they presented adequate original primary data to calculate a receiver operating
      characteristic (ROC) curve in subjects possessing histopathologically verified
      diagnoses. Articles containing subjects with concurrent, non-prostate-related
      genitourinary conditions were excluded. Percent free PSA sensitivity,
      specificity, ROC curves, and positive likelihood ratios were calculated for all
      PSA ranges and for the reflex range of PSA between 4 and 10 ng/mL. RESULTS: Among
      the 41 studies, containing 19,643 subjects, area under the curve for %fPSA was
      0.70 for all PSA levels, decreasing to 0.68 in the reflex range. A test cutoff of
      20% would lead to 92% sensitivity and 23% specificity. Positive likelihood ratios
      ranged from 1.0 to 4.0, exceeding 2.0 at %fPSA of 15% or less. Within the reflex
      range, however, likelihood ratios exceeded 2.0 only at %fPSA of 7% or less.
      CONCLUSIONS: Percent free PSA can be a useful adjunct to PSA for primary prostate
      cancer screening only under certain defined situations. In the "gray zone," or
      reflex range, of PSA testing, %fPSA improves clinical information only when
      levels reach extreme values.

PMID- 16600353
TI  - In vitro evaluation of ureteral stent compression.
AB  - OBJECTIVES: To evaluate the force required to radially compress ureteral stents
      and the impact of compression on stent performance across a broad range of stent
      sizes and manufacturers. METHODS: Fourteen ureteral stents ranging in size from
      6F to 10.3F were evaluated for radial compression using an MTS Micro Bionix
      Testing System using Testworks II software, 5N load cell, vibration isolation
      table, and socket set screws with rounded caps. Radial compression was exerted in
      0.2-mm increments. Cycles of compression and a 100-second hold time were repeated
      for each stent to maximal compression. Three trials were completed for each
      stent. The Young's Modulus, E, was calculated from each trial using the
      engineering stress. Simultaneous flow data using normal saline were collected for
      the Amplatz stent. RESULTS: The Cook C-Flex (E = 30,355 +/- 910 Pa), Microvasive
      Percuflex Plus 6F (E = 28,973 +/- 250 Pa), Cook EndoSof (E = 28,403 +/- 471 Pa),
      and Fossa Open Lumen (E = 28,627 +/- 5,338) were the most resistant to
      compression and the Cook Amplatz 10.2F (E = 11,922 +/- 220 Pa) and Microvasive
      Percuflex Plus 10.3F (E = 8,247 +/- 286 Pa) were the least resistant to
      compression. Stress relaxation occurred similarly in all stents. Flow through the
      Cook Amplatz stent decreased at a rate of 5 mL/s/mm of compression linearly (R2 =
      0.95). CONCLUSIONS: Stents resistant to radial compression are critical for
      function in the face of extrinsic ureteral obstruction. The Cook C-Flex ureteral
      stent resisted extrinsic compressive forces best. Although large-lumen stents are
      often used in this clinical situation, they were the most susceptible to
      compressive forces.

PMID- 16600354
TI  - Re: intraperitoneal catheter outcomes in a phase III trial of intravenous versus
      intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal
      cancer: a Gynecologic Oncology Group Study.

PMID- 16600355
TI  - Topographic distribution of sentinel lymph nodes in patients with cervical
      cancer.
AB  - BACKGROUND: Since the introduction of the sentinel concept in cervical cancer in
      1999, various studies have been demonstrated the feasibility, detection rate and
      sensitivity and rate of false-negative sentinel lymph nodes (SLN). There are only
      limited data regarding the mapping of the removed SLN. A correlation between the
      localization of SLN and the tumor stage, histology or marker substance has never
      been investigated. METHODS: Between 2/2000 and 6/2005, the SLN distribution of
      151 patients with histologically confirmed cervical cancer (FIGO stages IA n =
      21, IB n = 95, IIA n = 14, IIB n = 18, IIIB n = 2, IVA n = 1), who participated
      in the ongoing "Uterus 3" sentinel study of the German Association of Gynecologic
      Oncologists (AGO), was retrospectively analyzed with respect to the histology,
      tumor stage and detection substance. The tumors comprised mostly of squamous cell
      carcinomas (75.5%) with a smaller fraction of adenocarcinomas (24.5%). RESULTS:
      Altogether, 406 SLN, an average of 2.7 (1-7) SLN per patient, were removed. More
      than one SLN was detected in 111 patients (73.5%). SLN were found unilaterally in
      70 patients (46.4%) und bilaterally in 81 patients (53.6%). SLN sites were
      paraaortic in 4%, common iliac in 5%, external iliac in 5%, internal iliac in 8%,
      interiliac in 71% and parametric in 7%. Irrespective of the detection drug
      applied, most SLN were interiliac (blue 70%, TC 67%, TC and blue 71%). Combined
      application of technetium and blue dye revealed significantly more SLN in the
      paraaotic region (P = 0.006). Adenocarcinomas and squamous carcinomas did not
      differ in the distribution of SLN (P = 0.205). The majority of SLN are interiliac
      in all tumor stages (FIGO IA 76%, IB 68%, IIA 61%, IIB 83%, III and IV 88%).
      CONCLUSIONS: Removal of SLN in the external iliac, interiliac and obturator area
      enables evaluation of more than 80% of all SLN. The pattern of SLN is independent
      from histology and tumor stage. Combined use of technetium and blue dye detects
      sentinels more frequently in the paraaortic region than a single marker.

PMID- 16600356
TI  - A review of advances in the use of the GnRH agonist deslorelin in control of
      reproduction.
AB  - The prevention of breeding in animals using GnRH analogues has been the object of
      research over many years. Recently, a new drug delivery formulation was developed
      which enabled the development of products that could be commercialised for
      veterinary use. The formulation has now been approved in certain countries for
      use in male dogs, and applications are being expanded to cover repeat usage,
      extended duration, use in females, other indications and other animal species.
      With respect to repeat usage, dogs have been re-implanted for four consecutive
      doses and monitored until they returned to normal steroidogenesis. All dogs
      returned to normal steroidogenesis following cessation of treatment. In females,
      it was previously shown that implanted bitches with progesterone < 5 ng/mL at the
      time of implantation had an induced estrus. In a new study at Chulalongkorn
      University, implanting female pups at around 4 mo prevented this occurrence,
      whereas implantation at 7 mo did not.

PMID- 16600357
TI  - An acquired deficit of audiovisual speech processing.
AB  - We report a 53-year-old patient (AWF) who has an acquired deficit of audiovisual
      speech integration, characterized by a perceived temporal mismatch between speech
      sounds and the sight of moving lips. AWF was less accurate on an auditory digit
      span task with vision of a speaker's face as compared to a condition in which no
      visual information from the lower face was available. He was slower in matching
      words to pictures when he saw congruent lip movements compared to no lip
      movements or non-speech lip movements. Unlike normal controls, he showed no
      McGurk effect. We propose that multisensory binding of audiovisual language cues
      can be selectively disrupted.

PMID- 16600358
TI  - Gender differences in the self-defining activities and identity experiences of
      adolescents and emerging adults.
AB  - Activity participation provides a unique context for adolescents and emerging
      adults to explore interests, talents, and skills and for identity work to occur.
      Research has found consistent gender differences in the types of activities in
      which males and females participate. The current study drew on Eudaimonistic
      identity theory to examine the subjective identity-related experiences of
      personal expressiveness, flow experiences, and goal-directed behaviour [Waterman,
      1984; Waterman, 2004. Finding someone to be: Studies on the role of intrinsic
      motivation in identity formation. Identity, 4, 209-228] within a special type of
      activity, self-defining activities, or those activities that participants
      identify as being important to who they are as a person. This study also tested
      for gender and country differences in a sample of 572 adolescents and emerging
      adults from the United States, Italy, and Chile. Findings indicate gender and
      country differences in the types of self-defining activities for males and
      females, but no gender differences in the reported identity-related experiences
      within those activities. This finding held across the three countries. Results
      from Multivariate Analyses of Variance also indicate that identity-related
      experiences differ significantly across seven broad activity classes. Findings
      are discussed in the context of the growing literature on adolescent activity
      involvement and time use, gender, and their relations to identity exploration.

PMID- 16600359
TI  - How is impulsivity related to depression in adolescence? Evidence from a French
      validation of the cognitive emotion regulation questionnaire.
AB  - The aim of this study was to validate a French version of the Cognitive Emotion
      Regulation Questionnaire (CERQ; Garnefski, N., Kraaij, V., & Spinhoven, P., 2001.
      Negative life events, cognitive emotion regulation and emotional problems.
      Personality and Individual Differences, 30, 1311-1327) and to explore its
      relationships with impulsivity and depression. Teenagers from a junior secondary
      (n=107, 13-16 years) and a secondary school (n=110, 15-19 years) completed the
      CERQ, which assesses regulation strategies in response to negative events. The
      secondary school adolescents also completed the UPPS Impulsive Behavior Scale
      (Whiteside, S. P., & Lynam, D. R., 2001. The five factor model and impulsivity:
      Using a structural model of personality to understand impulsivity. Personality
      and Individual Differences, 30, 669-689) and the Reynolds Adolescent Depression
      Scale (Reynolds, W. M., 1987. Reynolds Adolescent Depression Scale: Professional
      manual. Odessa, FL: Psychological Assessment Resources). Factor analysis for the
      CERQ confirmed the presence of the nine original regulation strategies. In the
      secondary school students, impulsivity was related to depression. A path analysis
      revealed that regulation strategies mediated this relationship. The role of
      emotion regulation in the development of adolescent psychopathology is discussed.

PMID- 16600360
TI  - Identifying protein-protein interfacial residues in heterocomplexes using residue
      conservation scores.
AB  - Identifying protein-protein interfaces is crucial for structural biology. Because
      of the constraints in wet experiments, many computational methods have been
      proposed. Without knowing any information about the partner chains, a new method
      of predicting protein-protein interaction interface residues purely based on
      evolutionary information in heterocomplexes is proposed here. Unlike traditional
      approaches using multiple sequence alignment profiles to represent the
      conservation level for each residue, we make predictions based on the concept of
      residue conservation scores so that the dimension of the feature vector for each
      residue can be drastically reduced, at least 20 times less than conventional
      methods. Based on the representation approach, a simple linear discriminant
      function is used to make predictions, so the computational complexity of the
      whole prediction procedure can also be greatly decreased. By testing our approach
      on 69 heterocomplex chains, experimental results demonstrate the performance of
      our approach is indeed superior to current existing methods.

PMID- 16600361
TI  - The development of rapid fluorescence-based immunoassays, using quantum dot
      labelled antibodies for the detection of Listeria monocytogenes cell surface
      proteins.
AB  - Listeria monocytogenes is an important food-borne pathogen with an extremely high
      mortality rate (approximately 30%). Therefore, a highly sensitive, reproducible
      and rapid assay for its detection is vital. L. monocytogenes cells employ two
      surface bound proteins, Internalin A (InlA) and Internalin B (InlB) to promote
      invasion into host cells. Recombinant forms of both proteins were previously
      cloned and expressed in Escherichia coli. In this paper we describe how the InlB
      protein was sub-divided into three shorter overlapping peptide fragments yielding
      truncated functional protein of M(R) 23, 35 and 45 kDa, respectively.
      Purification of the InlB fragments by immobilised metal affinity chromatography
      (IMAC) was optimised and confirmed by electrophoresis and Western blotting.
      Identification of the antibody binding regions was achieved by probing the
      expressed polypeptide domains with a panel of antibodies and antibody fragments.
      The cloned peptide fragments were also used to develop novel fluorescence-based
      immunoassays incorporating quantum dots. The application of quantum dot-labelled
      anti-InlA monoclonal antibodies for immunostaining L. monocytogenes was also
      demonstrated.

PMID- 16600362
TI  - Preparation and characterization of solid lipid nanoparticles loaded traditional
      Chinese medicine.
AB  - Ultrasonication was employed to prepare solid lipid nanoparticles (SLN). The
      model traditional Chinese medicine, tetrandrine (TET), was incorporated into SLN.
      The TET-loaded SLN (TET-SLN) were spherical in the photograph of transmission
      electron microscope (TEM). The particle size measured by laser diffraction (LD)
      was found to be 157.3+/-8.2nm. Zeta potential analyzer suggested the zeta
      potential of TET-SLN was -29.36+/-3.68mV in distilled water. The entrapment
      efficiency (EE%) was determined with the sephadex gel chromatogram and high
      performance liquid chromatogram (HPLC), and up to 90.59% of TET was incorporated.
      Stability evaluation showed relatively long-term stability with only slight
      particle growth (P>0.05) after storage at room temperature for 4 weeks.
      Therefore, ultrasonication is demonstrated to be a simple, available and
      effective method to prepare high quality SLN loaded traditional Chinese medicine.

PMID- 16600364
TI  - The in vitro inhibition of multidrug resistance by combined nanoparticulate
      titanium dioxide and UV irradition.
AB  - The appearance of drug-resistant (especially, multidrug-resistant (MDR)) tumor
      cells is a major obstacle to the success of chemotherapy; thus, the development
      of effective anti-MDR agents plays an important role in the tumor therapy. In
      this report, the considerable effect of nano-TiO2 and UV illumination on the drug
      resistance of target cancer cells has been explored, and the fresh evidence from
      the fluorescence spectroscopy and microscopy as well as electrochemical studies
      demonstrates the significant enhancement effect of nano-TiO2 to the drug uptake
      by drug-resistant leukemia cells. Besides, it is also observed that the
      combination of the nano-TiO2 and UV irradiation with the accompanying anticancer
      drug daunorubicin could provoke some considerable changes of the cell membrane of
      the target leukemia cells, which indicates that nano-TiO2 could not only increase
      the drug accumulation in target cancer cells, but also act as an effective anti
      MDR agent to inhibit the relative drug resistance.

PMID- 16600363
TI  - Enzymatic degradation of poly(ether urethane) and poly(carbonate urethane) by
      cholesterol esterase.
AB  - This study examined the effect of cholesterol esterase (CE) on the degradation of
      commercial poly(ether urethane) (PEU) and poly(carbonate urethane) (PCU).
      Unstrained PEU and PCU films were incubated in 400 U/mL CE solution or a buffer
      control for 36 days. The study used a concentration of cholesterol esterase that
      was considerably higher than the estimated physiological level in order to
      accelerate degradation. However, characterization of treated polyurethane films
      with SEM, attenuated total reflectance Fourier transform infrared (ATR-FTIR) and
      GPC analysis revealed only a small loss in surface soft segment content.
      Comparison with implanted PEU and PCU films led to the conclusion that any effect
      of enzymatic hydrolysis was confined to the immediate surface, and the magnitude
      of the effect was too small to contribute significantly to in vivo degradation.
      The study confirmed that oxidation, rather than enzymatic hydrolysis, is the
      primary mechanism responsible for the observed biodegradation of PEU and PCU. The
      oxidative H(2)O(2)/CoCl(2) treatment continues to accurately predict the long
      term biostability of polyurethanes.

PMID- 16600365
TI  - Osteogenic differentiation of mesenchymal stem cells in self-assembled peptide
      amphiphile nanofibers.
AB  - The proliferation and differentiation of mesenchymal stem cells (MSC) was
      investigated in a three dimensional (3-D) network of nanofibers formed by self
      assembly of peptide-amphiphile (PA) molecules. PA was synthesized by standard
      solid phase chemistry that ends with the alkylation of the NH(2) terminus of the
      peptide. The sequence of arginine-glycine-aspartic acid (RGD) was included in
      peptide design as well. A 3-D network of nanofibers was formed by mixing cell
      suspensions in media with dilute aqueous solution of PA. Scanning electron
      microscopy (SEM) observation revealed the formation of fibrous assemblies with an
      extremely high aspect ratio and high surface areas. When rat MSC were seeded into
      the PA nanofibers with or without RGD, larger number of cells attached was
      observed in the PA nanofibers including RGD. When measured to evaluate the
      osteogenic differentiation of MSC, the alkaline phosphatase (ALP) activity and
      osteocalcin content became maximum for the PA nanofibers including RGD compared
      with those without RGD, although both the values were significantly higher
      compared with those in the static tissue culture plate (2-D culture). We
      concluded that the attachment, proliferation, and osteogenic differentiation of
      MSC were influenced by PA nanofibers as the cell scaffold.

PMID- 16600366
TI  - Control of drug accessibility on functional polyelectrolyte multilayer films.
AB  - A surface coating based on polylysine/hyaluronic acid multilayers was designed
      and acted as a reservoir for an antiproliferative agent, paclitaxel (Taxol).
      Absolutely no chemical modification of polyelectrolytes or of the drug was needed
      and the final architecture was obtained in an extremely simple way using the
      layer-by-layer method. The paclitaxel dose available for human colonic
      adenocarcinoma cells HT29 seeded on the films could be finely tuned. Moreover,
      the accessibility of the drugs was controlled by adding on the top of the drug
      reservoir a capping made of synthetic polyelectrolyte multilayers. This capping
      was also required to allow adhesion of HT29 cells. Paclitaxel activity was
      maintained after embedding in the polyelectrolyte multilayers and cellular
      viability could be reduced by about 80% 96 h after seeding. The strategy
      described in this paper could be valuable for various other drug/cell systems.

PMID- 16600367
TI  - Degradation behavior of dextran hydrogels composed of positively and negatively
      charged microspheres.
AB  - This paper reports on the degradation behavior of in situ gelling hydrogel
      matrices composed of positively and negatively charged dextran microspheres.
      Rheological analysis showed that, once the individual microspheres started to
      degrade, the hydrogel changed from a mainly elastic to a viscoelastic network. It
      was shown with gels composed of equal amounts of cationic and anionic
      microspheres, that both a higher crosslink density of the particles and a
      decrease in water content of the hydrogels resulted in a slower degradation,
      ranging from 65 to 140 days. Dispersions containing cationic, neutral or anionic
      microspheres completely degraded within 30, 55 or 120 days, respectively. The
      microspheres were loaded with rhodamine-B-dextran and degradation was studied
      with confocal microscopy and fluorescence spectroscopy. After a lag time of 3
      days rhodamine-B-dextran started to release from the positive microspheres with a
      50% release after 16 days. In contrast, release of rhodamine-B-dextran from the
      negative microspheres started after 10 days with a 50% release after 36 days. The
      faster degradation of the positively charged microspheres as compared to the
      negatively charged microspheres is attributed to stabilization of the transition
      state in the hydrolysis process by the protonated tertiary amine groups present
      in the cationic microspheres. On the other hand, the presence of negatively
      charged groups causes repulsion of hydroxyl anions resulting in a slower
      degradation. Combining the oppositely charged microspheres in different ratios
      makes it possible to tailor the network properties and the degradation behavior
      of these hydrogels, making them suitable for various applications in drug
      delivery and tissue engineering.

PMID- 16600368
TI  - Endothelial expression of Fc gamma receptor IIb in the full-term human placenta.
AB  - In the third trimester, human placental endothelial cells express Fc gamma
      receptor IIb (FcgammaRIIb). This expression is unique because FcgammaRIIb is
      generally expressed on immune cells and is typically undetectable in adult
      endothelial cells. Recently, we found a novel FcgammaRIIb-defined, IgG-containing
      organelle in placental endothelial cells; this organelle may be a key structure
      for the transcytosis of IgG across the endothelial layer. In this study, we
      verify the expression of FcgammaRIIb in endothelial placenta cells and use
      reverse transcriptase-polymerase chain reaction (RT-PCR) and sequencing analyses
      to define the expressed FCGR2B mRNA transcript variant. We also investigated the
      distribution of FCGR2B mRNA and protein within the vascular tree of the full-term
      human placenta by RT-PCR and quantitative microscopy. The mRNA sequence of FCGR2B
      expressed specifically in placental endothelial cells is that of transcript
      variant 2. FcgammaRIIb expression and synthesis occur throughout the placental
      vascular tree but do not extend into the umbilical cord. This study provides
      additional information on FcgammaRIIb expression in the human placenta.

PMID- 16600369
TI  - Characteristics of transcription-regulatory elements for gene expression from
      plasmid vectors in human trophoblast cell lines.
AB  - Nonviral gene delivery systems are useful for basic research in trophoblasts. In
      these systems, gene expression is regulated by a cassette of regulatory elements
      within the plasmid, and the transcriptional activity differs among cell lines. In
      the present study, we used BeWo and JAR human trophoblast cell lines to
      systematically compare the transcriptional activities of several expression
      cassettes and those of a control plasmid made up of a simian virus 40 (SV40)
      promoter, a polyadenylation (PA) signal, and an enhancer. We also found that
      insertion of intron elements enhanced transcriptional activities in the following
      order: intron A>hybrid beta-globin-immunoglobin intron>no intron. Of several PA
      signals tested including those from SV40, bovine growth hormone, and the minimal
      rabbit beta-globin, the latter had the highest transcriptional activities (3.9-
      and 26-fold over control plasmid in BeWo and JAR cells, respectively). Addition
      of a second enhancer increased the transcriptional activity in these cells. We
      also found that gene expression level can be controlled by selecting the
      expression cassette. These results should be useful for further transgene
      experiments in BeWo and JAR cells.

PMID- 16600370
TI  - Inducer and inhibitor: "antagonistic duality" of p21 in differentiation.

PMID- 16600371
TI  - Stress-induced in vitro apoptosis of native human acute myelogenous leukemia
      (AML) cells shows a wide variation between patients and is associated with low
      BCL-2:Bax ratio and low levels of heat shock protein 70 and 90.
AB  - Spontaneous in vitro apoptosis reflects a true biological heterogeneity between
      patients which has to be considered when in vitro models are used to study
      regulation of apoptosis in native human AML cells. Even though the balance
      between pro- and anti-apoptotic signaling seems to have a prognostic impact in
      AML, the possible clinical relevance of spontaneous apoptosis remains to be
      clarified. High apoptosis/low viability was associated with low levels of heat
      shock proteins 70 and 90 as well as low Bcl-2:Bax ratio for patients
      heterogeneous with regard to morphology, membrane molecule expression, genetic
      abnormalities and response to therapy.

PMID- 16600372
TI  - Who disrupts from placement in foster and kinship care?
AB  - OBJECTIVE: To identify reliable, inexpensive predictors of foster care placement
      disruption that could be used to assess risk of placement failure. METHODS: Using
      the Parent Daily Report Checklist (PDR), foster or kinship parents of 246
      children (5-12 years old) in California were interviewed three times about
      whether or not their foster child engaged in any of the 30 problem behaviors
      during the previous 24 h. PDR was conducted during telephone contacts (5-10 min
      each) that occurred from 1 to 3 days apart at baseline. Disruptions were tracked
      for the subsequent 12 months. Other potential predictors of disruption were
      examined, including the child's age, gender, and ethnicity, the foster parent's
      ethnicity, the number of other children in the foster home, and the type of
      placement (kin or non-kin). RESULTS: Foster/kin parents reported an average of
      5.77 child problems per day on the PDR checklist. The number of problem behaviors
      was linearly related to the child's risk of placement disruption during the
      subsequent year. The threshold for the number of problem behaviors per day that
      foster and kinship parents tolerated without increased risk of placement
      disruption for these latency-aged children was 6 or fewer. Children in non-kin
      placements were more likely to disrupt than those in kinship placements. There
      was a trend for increased risk of disruption as the number of children in the
      home increased. CONCLUSIONS: The PDR Checklist may be useful in predicting which
      placements are at most risk of future disruption, allowing for targeted services
      and supports.

PMID- 16600373
TI  - Does the wording of the mandate to report suspected child abuse serve as another
      barrier to child abuse reporting?

PMID- 16600374
TI  - Animal cruelty by children exposed to domestic violence.
AB  - OBJECTIVE: The first objective of this study was to determine if children exposed
      to domestic violence were significantly more likely to be cruel to animals than
      children not exposed to violence. The second was to determine if there were
      significant age and gender differences between children who were and were not
      cruel to animals. METHOD: A community sample of 47 mothers with two children and
      a history of domestic violence were compared to a matched sample of 45 mothers
      with two children who did not have such a history. RESULTS: Children exposed to
      domestic violence were significantly more likely to have been cruel to animals
      than children not exposed to violence. The age and gender of children who were
      cruel to animals did not differ from children who were not cruel to animals.
      However, exposed children cruel to animals were significantly older than non
      exposed children cruel to animals. CONCLUSION: Animal cruelty by children is
      correlated with exposure to domestic violence.

PMID- 16600375
TI  - Perceived neighborhood social disorder and residents' attitudes toward reporting
      child physical abuse.
AB  - OBJECTIVE: This study aimed to explore the relationship between perceived
      neighborhood social disorder and attitudes toward reporting child physical abuse.
      METHOD: Data from a national probabilistic sample (N=9,759) were used. Responses
      about the perception of neighborhood social disorder, perceived frequency of
      child physical abuse in Spanish families, and willingness to report a case of
      child physical abuse to the police were collected through face-to-face interviews
      in respondents' homes. RESULTS: Multivariate logistic regression analysis showed
      that perceived neighborhood social disorder was negatively related to residents'
      attitudes toward reporting child physical abuse. These results take into account
      the potential confounding effects of gender, age, socio-economic status,
      educational level, size of city, and perceived frequency of child physical abuse
      on reporting attitudes. CONCLUSION: Results illustrate the important role that
      community characteristics may play in processes relevant to the prevention of
      child maltreatment such as residents' attitudes towards reporting child physical
      abuse, and suggest that especially disadvantaged communities characterized by
      high levels of social disorder need to be specifically targeted if the aim is to
      increase the capacity to prevent child maltreatment in the community.

PMID- 16600376
TI  - The role of key developmental variables in identifying sex offenders likely to
      fail in the community: an enhanced risk prediction model.

PMID- 16600377
TI  - Effect of heavy metal stress on proline, malondialdehyde, and superoxide
      dismutase activity in the cyanobacterium Spirulina platensis-S5.
AB  - This study investigated toxic impacts of lead, copper, and zinc over a
      concentration gradient of 0.05-0.20 mg/L on proline, malondialdehyde (MDA), and
      superoxide dismutase (SOD) in the cyanobacterium Spirulina platensis-S5. Despite
      a reduction in growth of the test microorganism, its MDA, SOD, and proline
      contents increased under the heavy metal stress, corresponding to the
      concentration of the metal ion in the culture medium. Increased amount of MDA was
      indicative of formation of free radicals in the test microorganism under heavy
      metals stress(es), while increased levels of SOD and proline pointed to the
      occurrence of a scavenging mechanism.

PMID- 16600378
TI  - The evolution of outpatient commitment in the USA: from conundrum to quagmire.
AB  - Outpatient commitment (OPC), a major form of involuntary community-based
      treatment, has evolved in the United States on a state-by-state basis amidst a
      storm of controversy. The polarizing debate that has gone on intensely about OPC
      for the last two decades has all too often been devoid of data. This article
      reviews the various arguments pro and con about OPC, and then examines the
      research on the effectiveness of OPC. Since the newest data seem to support OPC
      as a useful tool in dealing with specific subpopulations of persons with chronic
      mental illness, the paper examines the question of whether OPC is a legitimate
      use of government power. The most extensive analysis of this question to date has
      occurred in the New York State Courts which have supported the New York State OPC
      statute, Kendra's Law. The paper concludes with an examination of the future of
      OPC in the states, calling in particular for further research into the question
      of determining to whom, from a clinical point of view, should OPC be delivered.

PMID- 16600379
TI  - Linnaeus' herbarium cabinet: a piece of furniture and its function.
AB  - The Swedish 18th-century naturalist Carolus (Carl) Linnaeus is habitually
      credited with laying the foundations of modern taxonomy through the invention of
      binominal nomenclature. However, another innovation of Linnaeus' has largely gone
      unnoticed. He seems to have been one of the first botanists to leave his
      herbarium unbound, keeping the sheets of dried plants separate and stacking them
      in a purpose built-cabinet. Understanding the significance of this seemingly
      mundane and simple invention opens a window onto the profound changes that
      natural history underwent in the 18th century.

PMID- 16600380
TI  - A phage antibody to the active site of human placental alkaline phosphatase with
      higher affinity to the enzyme-substrate complex.
AB  - Selection of specific antibodies from large repertoires is of importance in
      generating antibodies to specific structural determinants and in studying
      structure-function relationships. Alkaline phosphatase (AP) has several isozymes
      with various degrees of homology and a range of common synthetic substrates. We
      have previously reported the generation of isozyme specific anti-enzyme
      antibodies to an oncofetal antigen, placental alkaline phosphatase (PLAP) by
      using a specific uncompetitive inhibitor, L-Phe-Gly-Gly along with the substrate
      para-nitrophenyl phosphate (pNPP), to elute scFvs from a phage-displayed
      immunoglobulin library. These antibodies were directed to the active site and
      inhibited enzyme activity. An uncompetitive inhibitor acts by stabilizing the
      enzyme-substrate (ES) complex. In the present work, we report the characteristics
      of a clone VE5, selected by the same method. This clone has a higher binding
      affinity for ES complex than for enzyme alone. This is true for all the three
      isozymes (placental, bone and intestinal) tested. However, the other synthetic
      small molecular substrate, disodium phenyl phosphate inhibits phage binding. The
      clone possibly binds to the conserved structures of the active site of the AP
      isozymes and the higher affinity binding to AP-pNPP complex reflects the method
      of selection. Such anti-enzyme antibodies have a possible potential role in
      dissecting structure-function relationship of enzymatic antigens.

PMID- 16600381
TI  - ZXDC, a novel zinc finger protein that binds CIITA and activates MHC gene
      transcription.
AB  - The class II trans-activator (CIITA) is recognized as the master regulator of
      major histocompatibility complex (MHC) class II gene transcription and
      contributes to the transcription of MHC class I genes. To better understand the
      function of CIITA, we performed yeast two-hybrid with the C-terminal 807 amino
      acids of CIITA, and cloned a novel human cDNA named zinc finger, X-linked,
      duplicated family member C (ZXDC). The 858 amino acid ZXDC protein contains 10
      zinc fingers and a transcriptional activation domain, and was found to interact
      with the region of CIITA containing leucine-rich repeats. Over-expression of ZXDC
      in human cell lines resulted in super-activation of MHC class I and class II
      promoters by CIITA. Conversely, silencing of ZXDC expression reduced the ability
      of CIITA to activate transcription of MHC class II genes. Given the specific
      interaction between the ZXDC and CIITA proteins, as well as the effect of ZXDC on
      MHC gene transcription, it appears that ZXDC is an important regulator of both
      MHC class I and class II transcription.

PMID- 16600382
TI  - Saccharide-mediated interactions of boar sperm surface proteins with components
      of the porcine oviduct.
AB  - The role of boar seminal plasma proteins attached to the sperm plasma membrane
      during ejaculation has been studied in saccharide-mediated events in the female
      reproductive tract. Heparin-binding (Hep(+)) proteins (DQH sperm surface protein,
      and AQN and AWN spermadhesins) and their aggregated forms (fractions II and III)
      interacted more strongly with both oviductal epithelium cells and fluid than non
      heparin-binding (Hep(-)) proteins (PSP I and PSP II spermadhesins) and their
      heterodimer (fraction IV), and interactions correlate with affinity of these
      proteins to yeast mannan. Indirect immunofluorescence (IMF) showed that the AQN 1
      spermadhesin and fraction II bind to the apical glycocalyx of the ampulla, as
      well as the isthmic and uterine tubal junction regions of the oviductal sections.
      IMF demonstrated the recognition of AQN 1 and fraction II and mannosyl components
      of oviductal epithelium. We suggest that Hep(+) proteins (especially AQN 1,
      fraction II) on sperm could enable sperm binding to oviductal epithelium and thus
      participate in formation of the sperm oviductal reservoir. Interactions of Hep(+)
      proteins to oviductal epithelium were inhibited by mannan, hyaluronic acid and
      sialylated O-glycoproteins. No or slight inhibition was observed with sulphated
      polysaccharides (heparin, chondroitin sulphate) and simple monosaccharides.
      Besides that, attachment of boar seminal plasma proteins to oviductal epithelium
      cells was affected by oviductal fluid, the natural environment in the oviduct.
      Moreover, the ability of hyaluronic acid to inhibit the interaction of sperm
      surface proteins to the oviduct might play a role in sperm release from the
      oviductal reservoir and in the capacitation process.

PMID- 16600384
TI  - The efficacy of recombinant vaccines against white spot syndrome virus in
      Procambarus clarkii.
AB  - The effectiveness of oral, mock-, and immersion vaccination was investigated
      against white spot syndrome virus (WSSV) in crayfish. The most exposed WSSV
      envelope proteins VP19 and VP28 were used in different compositions and with
      different modes of applications. In experiment 1 crayfish were fed recombinant
      protein coated food pellets for 25 days, in experiment 2 the purified proteins
      were directly injected to them followed by one booster dose on 5th day and in
      experiment 3 the crayfish were left immersed in vaccines for 7 h. Experimental
      crayfish were challenged on 3rd and 21st days after last vaccination. The overall
      result showed that VP28 group has lowest cumulative mortality percentage
      accounting 39.6% at 3rd day and 39.83% at 21st day when injected and it was 43.2%
      and 49% when fed orally and 46.3% and 46.5% when immersed at 3rd and 21st days,
      respectively (p<0.05). In VP19 and VP28 (50:50) mixture, mock vaccination showed
      better performance (36.5%) over immersion (53%) and oral vaccination (53.2%) when
      challenged on 3rd day and mock vaccination (36.50%) followed by oral (51%) and
      immersion vaccination (56.5%) on 21st day as well. The VP19 recombinant mock
      vaccination group performed better (52.91% of 3rd day and 56.46% of 21st day)
      than oral (76% of 3rd day and 82% of 21st day) and immersion (83% of 3rd day and
      86.3% of 21st day) vaccine groups. All the experimental groups except VP19 were
      significantly different (p<0.05) from the control groups. A positive cumulative
      effect was observed when VP28 was mixed with VP19 in equal proportion in all the
      experimental trials, which shows the effectiveness of VP19 as a vaccine component
      too. In the present trial on the basis of cumulative mortality percentage it is
      found that mock-vaccination group is more effective than the oral vaccination and
      immersion vaccination. It also suggests that specific memory exists in crayfish
      and the effects of VP28 are significant. The effect of VP19 along with VP28 has
      also shown significant effect against WSSV.

PMID- 16600383
TI  - Macrophage-activating lipopeptide-2 induces cyclooxygenase-2 and prostaglandin
      E(2) via toll-like receptor 2 in human placental trophoblast cells.
AB  - We have examined whether toll-like receptor (TLR)2-mediated stimulation by
      macrophage-activating lipopeptide-2 (MALP-2), originally purified from Mycoplasma
      fermentans, induces cyclooxygenase (COX)-2 and prostaglandin (PG)E(2) in human
      placental trophoblast cells. The signaling mechanism by which MALP-2 exerts its
      effect has also been examined. Human placental trophoblast cells isolated from
      term placenta were used. TLR expression in trophoblast cells was confirmed by
      multiplex PCR and immunocytochemistry, and examined whether MALP-2 induces COX-2
      and PGE(2) by Northern blotting, RT-PCR, Western blotting and ELISA,
      respectively. The activation of NF-kappaB and MAP kinases (ERK1/2 and p38) was
      examined by Western blotting. The effects of inhibitors of NF-kappaB, MEK1/2 and
      p38 on MALP-2-induced PGE(2) production were also evaluated. TLR2, TLR6 and TLR4
      were expressed in human placental trophoblast cells. MALP-2 significantly induced
      COX-2 expression and enhanced PGE(2) production in a dose-dependent manner. MALP
      2 induced the activation of NF-kappaB, ERK1/2 and p38 MAPK. Inhibitors of NF
      kappaB, MEK1/2 and p38 blocked MALP-2-inducible PGE(2) production. TLR2-mediated
      stimulation by MALP-2 induces COX-2 and PGE(2) in human placental trophoblast
      cells via NF-kappaB and MAP kinases pathways.

PMID- 16600385
TI  - Immunoglobulin gene analysis in polyneuropathy associated with IgM monoclonal
      gammopathy.
AB  - Antineural antibody activity is the implicated pathogenic mechanism in
      polyneuropathy associated with monoclonal gammopathy. Recognition of antigen
      depends on immunoglobulin variable regions, encoded by V genes. We studied
      V(H)DJ(H) and V(L)J(L) gene use in monoclonal B cells by clonal analysis in 20
      patients with polyneuropathy and IgM monoclonal gammopathy. V genes associated
      with bacterial responses appear over-represented and V(H)3-23 was preferentially
      used, without association with specific D, J(H) or V(L)J(L). V genes revealed
      somatic mutation and intraclonal variation was found in 9 of 20 patients.
      Polyneuropathy associated with monoclonal gammopathy may be caused by an immune
      response to bacterial antigens, which recruit somatically mutated autoreactive B
      cells.

PMID- 16600386
TI  - Clinical proteomics: searching for better tumour markers with SELDI-TOF mass
      spectrometry.
AB  - Recently, the focus of cancer research has expanded from genetic information in
      the human genome to protein expression analyses. Because this 'proteome' reflects
      the state of a cell, tissue or organism more accurately, much is expected from
      proteomics to yield better tumour markers for disease diagnosis and therapy
      monitoring. Some current proteomic technologies are particularly suitable for
      protein profiling in the search for new biomarkers. Surface-enhanced laser
      desorption ionization time-of-flight mass spectrometry has been used frequently,
      highlighting many new proteins as biomarkers (e.g. for ovarian, breast, prostate
      and colorectal cancer). However, it is becoming increasingly recognized that
      reproducibility and validation of these biomarkers should be addressed carefully,
      as should their origin and identity. If these efforts are made, protein profiling
      can contribute to the better diagnosis of patients and the optimization of their
      treatment.

PMID- 16600387
TI  - TACE-dependent EGF receptor activation in angiotensin-II-induced kidney disease.
AB  - Angiotensin II (Ang II) has been implicated in the development of cardiovascular
      disorders and chronic kidney disease (CKD). Ang II causes renal lesions through
      the activation of tumor necrosis factor (TNF)-alpha-converting enzyme (TACE, also
      called a disintegrin and a metalloproteinase domain 17) and the release of
      transforming growth factor (TGF)-alpha, which binds to and activates the
      epidermal growth factor receptor. Renal lesions such as glomerulosclerosis,
      tubular atrophy, fibrosis, mononuclear cell infiltration and proteinuria
      following chronic Ang II infusion are substantially reduced in mice lacking TGF
      alpha and those given a specific TACE inhibitor. These findings indicate that the
      selective inhibition of renal TACE could have therapeutic potential in the
      treatment of CKD.

PMID- 16600388
TI  - Computational neuropharmacology: dynamical approaches in drug discovery.
AB  - Computational approaches that adopt dynamical models are widely accepted in basic
      and clinical neuroscience research as indispensable tools with which to
      understand normal and pathological neuronal mechanisms. Although computer-aided
      techniques have been used in pharmaceutical research (e.g. in structure- and
      ligand-based drug design), the power of dynamical models has not yet been
      exploited in drug discovery. We suggest that dynamical system theory and
      computational neuroscience--integrated with well-established, conventional
      molecular and electrophysiological methods--offer a broad perspective in drug
      discovery and in the search for novel targets and strategies for the treatment of
      neurological and psychiatric diseases.

PMID- 16600389
TI  - Genetic diseases associated with heterotrimeric G proteins.
AB  - Heterotrimeric G proteins couple receptors for diverse extracellular signals to
      effector enzymes or ion channels. Each G protein comprises a specific alpha
      subunit and a tightly bound betagamma dimer. Several human disorders that result
      from genetic G-protein abnormalities involve the imprinted GNAS gene, which
      encodes Gs alpha, the ubiquitously expressed alpha-subunit that couples receptors
      to adenylyl cyclase and cAMP generation. Loss-of-function and gain-of-function
      mutations, in addition to imprinting defects, of this gene lead to diverse
      clinical phenotypes. Mutations of GNAT1 and GNAT2, which encode the retinal G
      proteins (transducins), are rare causes of specific congenital visual defects.
      Common polymorphisms of the GNAS and GNB3 (which encodes Gbeta3) genes have been
      associated with multigenic disorders (e.g. hypertension and metabolic syndrome).
      To date, no other G proteins have been implicated directly in human disease.

PMID- 16600390
TI  - Fluorescent poliovirus for flow cytometric cell surface binding studies.
AB  - Specific cell-surface binding is the essential first step for cellular invasion
      by viruses. To understand this process, various methods to evaluate binding
      properties of viruses to cells have been developed. However, many rely on
      radioactive labeling or indirect immunofluorescence. The development of a novel
      fluorescence binding assay for poliovirus is described. Poliovirus (type 1
      Mahoney or Sabin) was labeled directly with fluorescein using a commercially
      available fluoresceination kit. Fluorescently labeled poliovirus was bound to its
      specific receptor on Hela or U937 cells and detected by flow cytometric analysis.
      Specific binding and infectivity was retained, although reduced, depending on the
      extent of fluoresceination. Therefore, depending on the users' requirements, the
      extent of fluoresceination must be titrated carefully to achieve maximal
      fluorescence and minimal functional destruction. It is likely that this method
      may be useful with other viruses.

PMID- 16600391
TI  - Transduction of avian cells with recombinant baculovirus.
AB  - Transduction of chicken and duck cells was examined by Ac-CMV-eGFP, a recombinant
      baculovirus capable of expressing an eGFP reporter gene under the control of the
      CMV promoter. The results showed that chicken and duck cells were transducible,
      as demonstrated by a flow cytometry assay. The transduction efficiency of duck
      cells was higher than that of chicken cells. The addition of histone deacetylase
      inhibitor sodium butyrate enhanced the expression levels of eGFP both in chicken
      and duck cells. Ac-CMV-eGFP is capable of transducing genes into a variety of
      chicken cells in organs such as liver, lung and kidney. Of three cells from
      different organs tested, the highest transduction was observed in lung cells
      (49.8%), followed by kidney cells (44%) and liver cells (43%). Only in chicken
      liver cells AcMNPV transduction was in a dose-dependent manner. It also showed
      that baculovirus enters the avian cells by endocytosis and is released into the
      cytoplasm by acid-induced fusion.

PMID- 16600392
TI  - Increasing prevalence of HIV-1 protease inhibitor-associated mutations correlates
      with long-term non-suppressive protease inhibitor treatment.
AB  - Treatment of human immunodeficiency virus type 1 with protease inhibitors (PIs)
      is associated with the emergence of resistance-associated mutations. Treatment
      characterized datasets have been used to identify novel treatment-associated
      protease mutations. In this study, we utilized two large reference laboratory
      databases (>115,000 viral sequences) to identify non-established resistance
      associated protease mutations. We found 20 non-established protease mutations
      occurring in 82% of viruses with a PI resistance score of 4-7, 62% of viruses
      with a resistance score of 1-3, and 35% of viruses with no predicted PI
      resistance. We correlated mutational prevalence to treatment duration in a
      treatment-characterized dataset of 2161 patients undergoing non-suppressive PI
      therapy. In the non-suppressed dataset, 24 mutations became more prevalent and
      three mutations became less prevalent after more than 48 months of non
      suppressive PI-therapy. Longer durations of non-suppressive treatment correlated
      with higher PI resistance scores. Mutations at eight non-established positions
      that were more common in viruses with the longest duration of non-suppressive
      therapy were also more common in viruses with the highest PI resistance score.
      Covariation analysis of 3036 protease amino acid substitutions identified 75
      positive and nine negative correlations between resistance associated positions.
      Our findings support the utility of reference laboratory datasets for
      surveillance of mutation prevalence and covariation.

PMID- 16600393
TI  - A sensitizing regimen of methamphetamine causes impairments in a novelty
      preference task of object recognition.
AB  - A neurotoxic regimen of methamphetamine impairs object recognition (OR) in rats.
      The present study investigated whether neurotoxicity is a necessary component of
      methamphetamine's effect on OR. Animals were exposed to a sensitizing regimen of
      methamphetamine, and were tested for OR one week, and locomotor behavior two
      weeks, later. Quantitative autoradiography was used to measure [(125)I]RTI-55
      binding to forebrain dopaminergic and serotonergic transporters. Methamphetamine
      treatment produced significant OR impairments (and increased locomotion), without
      reducing dopamine or serotonin transporter binding. This study supports the
      conclusion that factors other than monoamine terminal injury contribute to the
      methamphetamine-induced cognitive impairments.

PMID- 16600394
TI  - Beta-adrenoceptor mediated inhibition of long-term reward-related memory
      reconsolidation.
AB  - Well-consolidated fear-related memories, once retrieved, are susceptible to
      disruption and require reconsolidation in order to be maintained. We examined
      whether reactivated reward-related memories are also susceptible to interference
      by evaluating the effect of propranolol (PROP), a beta-adrenergic antagonist
      known to impair reconsolidation of fear-related memories, on context-induced
      sucrose seeking. PROP administration upon reactivation reduced sucrose seeking
      behaviour 3 weeks post-training, indicating that reconsolidation of reward
      related memories can be disrupted after a long post-training interval.

PMID- 16600395
TI  - Endocrine alteration in juvenile cod and turbot exposed to dispersed crude oil
      and alkylphenols.
AB  - Juvenile Atlantic cod (Gadus morhua) and turbot (Scophthalmus maximus) were
      exposed for 3 weeks in a continuous water flow to 0.5 ppm of dispersed North Sea
      crude oil, 0.5 ppm of dispersed North Sea crude oil spiked with 0.1 ppm of a
      mixture of alkylphenols (offshore oil production), and 30 ppb of nonylphenol
      (NP). As potential markers of endocrine alteration, key enzymatic activities
      involved in both synthesis (17beta-hydroxysteroid dehydrogenases and P450
      aromatase) and metabolism (liver UDP-glucuronosyltransferases (UGT) and
      sulfotransferases) of steroids were assessed together with circulating levels of
      testosterone and estradiol in plasma. NP-exposed turbot had lower ovarian P450
      aromatase, lower levels of testosterone and estradiol in plasma, and lower
      glucuronidation rates of sex steroids than those from the control group. In
      contrast, higher liver UGT-testosterone, and a trend towards higher P450
      aromatase was detected in oil-exposed specimens. Those exposed to the combination
      oil+alkylphenols had lower levels of estradiol in plasma than controls, and no
      significant effects on any the enzymatic activities tested was observed. All
      these alterations were more evident in turbot than in cod. In fact, apart from a
      higher glucuronidation rate of estradiol detected in the liver of NP-exposed cod,
      no significant differences were observed between control and exposed cod.

PMID- 16600396
TI  - Assessment of micronuclei induction in peripheral erythrocytes of fish exposed to
      xenobiotics under controlled conditions.
AB  - The aim of the present study was to standardize and to assess the predictive
      value of the cytogenetic analysis by MN test in fish erythrocytes as a biomarker
      for marine environmental contamination. MN frequency baseline in erythrocytes was
      evaluated in a number of fish species from a reference area (S. Teresa, La Spezia
      Gulf) and genotoxic potential of a number of common chemical contaminants and
      mixtures was determined in fish experimentally exposed in aquarium under
      controlled conditions. Fish (Scophthalmus maximus) were exposed for 3 weeks to 50
      ppb of single chemicals (dialkyl phthalate, bisphenol A, tetrabromodiphenyl
      ether), 30 ppb nonylphenol and mixtures (North Sea oil and North Sea oil with
      alkylated phenols). Chromosomal damage was determined as micronuclei (MN)
      frequency in fish erythrocytes. Nuclear anomalies such as blebbed, notched and
      lobed nuclei were also recorded. Significant increase in MN frequency was
      observed in erythrocytes of fish exposed to bisphenol A and
      tetrabromodiphenylether. Chemical mixture North Sea oil+alkylated phenols induced
      the highest MN frequency (2.95 micronucleated cells/1000 cells compared to 1
      MNcell/1000 cells in control animals). The study results revealed that
      micronucleus test, as an index of cumulative exposure, appears to be a sensitive
      model to evaluate genotoxic compounds in fish under controlled conditions.

PMID- 16600397
TI  - Specificity of the peroxisome proliferation response in mussels exposed to
      environmental pollutants.
AB  - Peroxisome proliferation has been proposed as novel biomarker of exposure to
      organic pollutants in aquatic organisms. Peroxisome proliferator compounds
      comprise a heterogeneous group of substances known for their ability to cause
      massive proliferation of peroxisomes and liver carcinogenesis in sensitive
      species such as rodents. Recently, several marine organisms (mussels and fish)
      have been shown as target species of peroxisome proliferators. In the present
      work, we aimed to investigate the specificity of the peroxisome proliferation
      response in mussels. For this purpose, mussels (Mytilus edulis) were exposed for
      three weeks to North Sea crude oil (NSO), a mixture of NSO, alkylphenols and
      extra PAHs (MIX), diallylphthalate (DAP), bisphenol-A (BPA) and
      tetrabromodiphenylether (TBDE), or transplanted for three weeks to four stations
      showing different copper concentrations in a copper mine. Peroxisome
      proliferation was assessed by measuring the activity of the peroxisomal beta
      oxidation enzyme acyl-CoA oxidase (AOX) and the volume density occupied by
      peroxisomes (V(VP)) in the digestive gland. Mussels exposed to NSO and MIX showed
      significantly increased AOX activities and V(VP) compared to control animals.
      Significantly higher V(VP) was also found in DAP and TBDE exposed mussels. V(VP)
      did not vary in mussels transplanted into a copper concentration gradient. Our
      results confirm the usefulness and specificity of peroxisome proliferation as a
      suitable biomarker of exposure to organic contaminants such as oil derived
      hydrocarbons, phthalate plasticizers and polybrominated flame retardants in
      mussels.

PMID- 16600398
TI  - Steroid levels and steroid metabolism in the mussel Mytilus edulis: the
      modulating effect of dispersed crude oil and alkylphenols.
AB  - Significant amounts of oil and alkylphenols are released into the sea by
      petroleum installations as a result of discharges of produced water. Some of
      these pollutants elicit estrogenic responses in fish, but their effects on the
      endocrine system of molluscs are largely unknown. In this study, mussels Mytilus
      edulis were exposed to North Sea oil (O) and the mixture of North Sea
      oil+alkylphenols (OAP), and the effects on tissue steroid levels and steroid
      metabolism (P450-aromatase and estradiol-sulfotransferase) were monitored. Levels
      of free testosterone and free estradiol were much higher in gonad tissue than in
      peripheral tissue, whereas esterified steroids (released after saponification)
      were of the same order of magnitude in both tissues. Levels of free steroids
      determined in gonads were not affected by exposure, but esterified steroids
      significantly increased in OAP exposed mussels (up to 2.4-fold). The sulfation of
      estradiol was investigated as a conjugation pathway, and increased activities
      were observed in digestive gland cytosol of both O and OAP exposure groups (up to
      2.8-fold). Additionally, increased P450-aromatase activity was determined in OAP
      exposed mussels (up to three-fold, both in gonad and digestive gland), but not in
      the O group. Altogether, the results indicate that North Sea oil leads to
      increased sulfation of estradiol, and that in combination with alkylphenols,
      additional alterations are observed: increased P450-aromatase, and increased
      levels of esterified-steroids in gonads. Nonetheless, mussels are able to
      maintain gonad concentrations of free steroids unaltered, possibly via
      homeostatic mechanisms such as the conjugation with fatty acid or the formation
      of sulphate conjugates.

PMID- 16600399
TI  - Isolation and characterization of mitochondrial ribosomes and ribosomal subunits
      from Leishmania tarentolae.
AB  - We have analyzed Leishmania tarentolae mitochondrial ribonucleoprotein (RNP)
      complexes using the 9S small subunit (SSU) rRNA and the 12S large subunit (LSU)
      rRNA as markers, and have identified a 50S RNP particle as the putative
      mitochondrial monosome, a 40S particle as the putative LSU and a 30S particle as
      the putative SSU. These assignments are supported by morphological analysis by
      cryo-electron microscopy and proteomics analyses by mass spectrometry. The
      presence of additional rRNA-containing particles complicated the analysis and
      most likely was the basis for previous difficulties in identification of these
      ribosomes; thus, in addition to the monosomes and their subunits, there are
      abundant stable 45S particles (SSU(*)) containing only 9S rRNA, which may
      represent homodimers of the SSU or SSU associated with additional proteins, and
      variable minor amounts of 65S and 70S particles, which represent homodimers of
      the LSU and SSU(*), respectively. These additional rRNA particles might be due to
      the lengthy mitochondrial isolation and ribosome isolation procedures or may be
      present in vivo and play yet undetermined roles.

PMID- 16600400
TI  - Identification and expression analysis of ABC protein-encoding genes in
      Toxoplasma gondii. Toxoplasma gondii ATP-binding cassette superfamily.
AB  - The ATP-binding cassette (ABC) transporters are one of the largest evolutionarily
      conserved families of proteins. They are characterized by the presence of
      nucleotide-binding domains (NBDs), which are highly conserved among organisms. In
      the present study, we used human and protozoan ABC sequences, and ATP-binding
      consensus motifs to screen the Toxoplasma gondii TwinScan2 predicted proteins
      database. We identified 24 ABC open reading frames (ORFs), whose deduced amino
      acid sequences exhibited all the typical biochemical features of the ABC family
      members. Fifteen of them clustered into five of the seven families of human ABC
      proteins: six ABCBs (drug, peptides and lipid export), two ABCCs (organic anion
      conjugates and drug export), one ABCE (Rnase L inhibitor, RLI, antibiotic
      resistance and translation regulation), one ABCF (drug resistance and regulation
      of gene expression) and five ABCGs (drug export and resistance). The nine other
      ORFs were represented by four ABCHs (energy-generating subunits), four SMCs
      (structural maintenance of chromosomes) and one member of unclear origin, whose
      closest homologue was the yeast Elf1 protein (mRNA export factor). A notable
      feature of the Toxoplasma ABC superfamily seems to be the absence of genes
      encoding ABCA and ABCD members. Expression analysis of ABC genes in tachyzoite
      and bradyzoite stages revealed the presence of ABC transcripts for all genes
      studied. Further research on the implication of these ABC proteins will increase
      our knowledge of the basic biology of Toxoplasma and provide the opportunity to
      identify novel therapeutic targets. To our knowledge, this is the first report of
      ABC transporters in T. gondii.

PMID- 16600401
TI  - Effect of sympathectomy and demedullation on increased myenteric and dorsal vagal
      complex Fos-like immunoreactivity by cholecystokinin-8.
AB  - Chemical sympathectomy with daily, intraperitoneal (IP) injections of
      guanethidine sulfate to adult rats, attenuated myenteric, but not dorsal vagal
      complex (DVC) Fos-like immunoreactivity (Fos-LI) by cholecystokinin-8 (CCK). This
      technique destroys only 60-70% of the sympathetic neurons, and spares the
      hormonal source of catecholamines, the adrenal medulla. The goal of the current
      study is to evaluate the effect of complete sympathectomy or destroying 100% of
      the sympathetic neurons by injecting guanethidine to 1-day-old pups (40 mg/kg
      daily for 5 weeks), and surgically removing the adrenal medulla. In the DVC,
      demedullation and sympathectomy-demedullation increased Fos-LI by CCK in the area
      postrema and nucleus of the solitary tract, but sympathectomy-demedullation
      increased it only in the area postrema. In the myenteric plexus, sympathectomy
      increased this response in the duodenum, and demedullation increased it in the
      duodenum and jejunum. On the other hand, sympathectomy-demedullation attenuated
      myenteric Fos-LI in the jejunum. These results indicate that catecholamines may
      play an inhibitory role on the activation of the DVC neurons by CCK. In the
      myenteric neurons, however, catecholamines may have both inhibitory and
      excitatory roles depending on the level of the intestine e.g., duodenum vs.
      jejunum. This may also indicate that CCK activates the enteric neurons by
      different mechanisms or through different pathways.

PMID- 16600402
TI  - Ghrelin-containing neuron in cerebral cortex and hypothalamus linked with the DVC
      of brainstem in rat.
AB  - Ghrelin is a newly discovered brain-gut peptide and an endogenous ligand for
      growth hormone secretagogues receptor (GHS-R). Ghrelin and GHS-R present
      extensively in central and peripheral tissues such as stomach, brain and other
      organs of rodent and human, which suggest it has multiple biological effects. It
      has been reported that ghrelin has significant role in the regulation of energy
      homeostasis, food intake and appetite. The organization of central circuitry
      appears to play an important role in integrating orexigenic effects of ghrelin,
      but the detail is not fully clear. In this study, we examined the expression of
      ghrelin, ghrelin mRNA and GHS-R mRNA in cerebrum and brainstem by RT-PCR and
      immunofluorescence histochemistry, and analyzed the connection among the cerebral
      cortex, hypothalamus, dorsal vagal complex (DVC). The results showed that the
      positive staining of ghrelin was found on the pyramidal neuron of layer V in the
      sensorimotor area of cerebral cortex, cingulate gyrus, as well as in the neuron
      of lateral hypothalamus (LH), PVN and ARC. The expression of ghrelin mRNA and GHS
      R mRNA were also found in the sensorimotor cortex and hypothalamus by method of
      RT-PCR. The GHS-R mRNA was also found in the DVC of medulla oblongata. Other
      finding is that the FG/ghrelin dual labeled neurons were found in LH of
      hypothalamus (not in cortex). The ghrelin-containing neuron in the LH projects
      its axon to the DVC with the method of retrograde tracing. In conclusion, the
      ghrelin neurons are located not only in hypothalamus (LH, PVN, ARC), but also in
      the cortex (sensorimotor area, cingular gyrus), and the fibers of ghrelin neurons
      in hypothalamus projected directly to the DVC. It suggests that ghrelin plays its
      role from hypothalamus to brainstem as a neurotransmitter or neuromodulator to
      regulate function of vagal nuclei in brainstem.

PMID- 16600403
TI  - Mapping the Ca2+ -dependent binding of an invertebrate homolog of protein
      phosphatase 4 regulatory subunit 2 to the small EF-hand protein, calsensin.
AB  - The EF-hand family of calcium-binding proteins regulates cellular signal
      transduction events via calcium-dependent interactions with target proteins.
      Here, we show that the COOH-terminal tail of the leech homolog of protein
      phosphatase 4 regulatory subunit 2 (PP4-R2) interacts with the small neuronal EF
      hand calcium-binding protein, Calsensin, in a calcium-dependent manner. Using two
      dimensional NMR spectroscopy and chemical shift perturbations we have identified
      and mapped the residues of Calsensin that form a binding surface for PP4-R2. We
      show that the binding groove is formed primarily of discontinuous hydrophobic
      residues located in helix 1, the hinge region, and helix 4 of the unicornate-type
      four helix structure of Calsensin. The findings suggest the possibility that
      calcium-dependent modulation of phosphatase complexes through interactions with
      small calcium-binding proteins may be a general mechanism for regulation of
      signal transduction pathways.

PMID- 16600404
TI  - An acute posterior myocardial infarction complicated with late pseudoaneurysm of
      the posterior wall.
AB  - Diagnostic image: An 80-year-old man is referred because of an acute posterior
      infarction. Because of persisting pain and apparition of a new murmur, an
      echocardiography is performed showing inferoposterolateral akinesis complicated
      by ventricular wall pseudoaneurysm. After discussing with patient and family,
      conservative therapy was continued. A clue for diagnosis of pseudoaneurysm is the
      presence of a systolic murmur.

PMID- 16600405
TI  - South Asian or Afro-Caribbean ethnicity is not associated with altered 1 min
      heart rate recovery estimates in suspected coronary artery disease patients.
AB  - Heart rate recovery following a Bruce exercise protocol provides prognostic
      information on survival. We investigated the impact of ethnicity on HRR in 271
      consecutive patients being assessed for CAD in three main ethnic groups
      (Caucasian (C); South Asian (SA); Afro-Caribbean (AC)). Our sample contained
      greater referral of younger, male South Asian subjects than would be expected on
      the basis of census data. The AC group had a low frequency of typical ischaemic
      pain. The SA sub-group, despite greater prevalence of diabetes, had marginally
      better HRR and a more preserved response to exercise. Multiple regression
      analysis revealed that age and not ethnicity was the main independent predictor
      of HRR (p=0.007) with all three ethnic sub-groups having a similar range of
      exercise time. There was no evidence of under referral of ethnic minorities.
      Ethnic effects in raw HRR data are most likely confounded by age.

PMID- 16600406
TI  - The oral transmission of Chagas' disease: an acute form of infection responsible
      for regional outbreaks.
AB  - Orally transmitted Chagas' disease is an ordinarily rare form of Trypanosome
      cruzi transmission, and responsible for regional outbreaks. Ingestion of
      contaminated material is generally associated with massive parasitic
      transmission, ultimately leading to acute myocarditis, with more severe clinical
      presentation at younger ages, and high death rates. Close monitoring of regional
      outbreaks by health agencies is mandatory in order to prevent recrudescence of
      the disease.

PMID- 16600407
TI  - Does metabolic syndrome attenuate the advantages of being a young woman regarding
      the risk of cardiovascular disease?

PMID- 16600408
TI  - Likelihood ratio estimation without a gold standard: a case study evaluating a
      brucellosis c-ELISA in cattle and water buffalo of Trinidad.
AB  - The likelihood ratio (LR) is a measure of association that quantifies how many
      more times likely a particular test result is from an infected animal compared to
      one that is uninfected. They are ratios of conditional probabilities and cannot
      be interpreted at the individual animal level without information concerning
      pretest probabilities. Their usefulness is that they can be used to update the
      prior belief that the individual has the outcome of interest through a
      modification of Bayes' theorem. Bayesian analytic techniques can be used for the
      evaluation of diagnostic tests and estimation of LRs when information concerning
      a gold standard is not available. As an example, these techniques were applied to
      the estimation of LRs for a competitive ELISA (c-ELISA) for diagnosis of Brucella
      abortus infection in cattle and water buffalo in Trinidad. Sera from four herds
      of cattle (n=391) and four herds of water buffalo (n=381) in Trinidad were
      evaluated for Brucella-specific antibodies using a c-ELISA. On the basis of
      previous serologic (agglutination) test results in the same animals, iterative
      simulation modeling was used to classify animals as positive or negative for
      Brucella infection. LRs were calculated for six categories of the c-ELISA
      proportion inhibition (PI) results pooled for cattle and water buffalo and
      yielded the following estimations (95% probability intervals): <0.10 PI, 0.05 (0
      0.13); 0.10-0.249 PI, 0.11 (0.04-0.20); 0.25-0.349 PI, 0.77 (0.23-1.63); 0.35
      0.499 PI, 3.22 (1.39-6.84); 0.50-0.749 PI, 17.9 (6.39-77.4); > or =0.75 PI, 423
      (129-infinity). LRs are important for calculation of post-test probabilities and
      maintaining the quantitative nature of diagnostic test results.

PMID- 16600409
TI  - Triptolide inhibits COX-2 expression via NF-kappa B pathway in astrocytes.
AB  - Previous investigations have showed that triptolide possessed potent anti
      inflammatory and immunosuppressive properties. In the present study, we examined
      the protective effects of triptolide on the inflammatory response induced by
      bacterial lipopolysaccharide (LPS) both in vivo and in vitro. Intrahippocampal
      injection of LPS (4 microg) in rats significantly increased the immunoreactivity
      of glial fibrillary acid protein (GFAP) and cyclooxygenase-2 (COX-2) in the
      injected region, which was reduced by pretreatment with triptolide (10-50
      microg/kg) for 5d. In the cultured human differentiated A172 astroglial cells,
      LPS (1mg/L) increased the expression of COX-2 mRNA and protein, the production of
      prostaglandin E(2) (PGE(2)) and the DNA binding activity of NF-kappa B, which
      were markedly attenuated by pretreatment with triptolide (0.2-5 microg/L) for 1h.
      These results suggested that the protective effect of triptolide on
      neuroinflammation is mediated by decreasing COX-2 expression, at least partly,
      via the inhibition of NF-kappa B signaling pathway.

PMID- 16600410
TI  - The dynamin-related mouse mitochondrial GTPase OPA1 alters the structure of the
      mitochondrial inner membrane when exogenously introduced into COS-7 cells.
AB  - Mutations in the dynamin family GTPase OPA1 are reportedly the cause of autosomal
      dominant optic atrophy, the most frequently occurring form of hereditary optic
      neuropathy. But although the involvement of structural abnormalities of the
      enzyme in this neurodegenerative disease is clear, little is known about the cell
      biological and biochemical functions of OPA1. Therefore, to better understand the
      pathogenesis of autosomal dominant optic atrophy, we precisely analyzed the
      effects of exogenously introducing mouse OPA1 (mOPA1) on mitochondrial morphology
      in COS-7 cells. We found that exogenously introducing wild type mOPA1 caused the
      mitochondria to become fragmented, and moreover caused the intermembrane space to
      accumulate on one side of the ring-shaped mitochondrial fragments. Immunoelectron
      microscopic observation of the mOPA1 transfectants confirmed that the structure
      of the mitochondrial inner membrane had changed dramatically, accumulating on one
      side of the mitochondrial structures. When cells were transfected with mOPA1
      containing a loss of function mutation (K301A) within the G1 GTP-binding domain,
      mitochondrial fragmentation still occurred. The markers for intermembrane space
      and matrix showed the similar morphology, which was distinctly different from the
      finding obtained with wild type mOPA1 transfectants. Notably, we also observed
      that the effect of two OPA1 missense mutations (E270K and D273A) associated with
      autosomal dominant optic atrophy elicit effects similar to those seen with the
      dominant negative K301A mutant.

PMID- 16600411
TI  - OMICS-driven biomarker discovery in nutrition and health.
AB  - While traditional nutrition research has dealt with providing nutrients to
      nourish populations, it nowadays focuses on improving health of individuals
      through diet. Modern nutritional research is aiming at health promotion and
      disease prevention and on performance improvement. As a consequence of these
      ambitious objectives, the disciplines "nutrigenetics" and "nutrigenomics" have
      evolved. Nutrigenetics asks the question how individual genetic disposition,
      manifesting as single nucleotide polymorphisms, copy-number polymorphisms and
      epigenetic phenomena, affects susceptibility to diet. Nutrigenomics addresses the
      inverse relationship, that is how diet influences gene transcription, protein
      expression and metabolism. A major methodological challenge and first pre
      requisite of nutrigenomics is integrating genomics (gene analysis),
      transcriptomics (gene expression analysis), proteomics (protein expression
      analysis) and metabonomics (metabolite profiling) to define a "healthy"
      phenotype. The long-term deliverable of nutrigenomics is personalised nutrition
      for maintenance of individual health and prevention of disease. Transcriptomics
      serves to put proteomic and metabolomic markers into a larger biological
      perspective and is suitable for a first "round of discovery" in regulatory
      networks. Metabonomics is a diagnostic tool for metabolic classification of
      individuals. The great asset of this platform is the quantitative, non-invasive
      analysis of easily accessible human body fluids like urine, blood and saliva.
      This feature also holds true to some extent for proteomics, with the constraint
      that proteomics is more complex in terms of absolute number, chemical properties
      and dynamic range of compounds present. Apart from addressing the most complex "
      ome", proteomics represents the only platform that delivers not only markers for
      disposition and efficacy but also targets of intervention. The Omics disciplines
      applied in the context of nutrition and health have the potential to deliver
      biomarkers for health and comfort, reveal early indicators for disease
      disposition, assist in differentiating dietary responders from non-responders,
      and, last but not least, discover bioactive, beneficial food components. This
      paper reviews the state-of-the-art of the three Omics platforms, discusses their
      implication in nutrigenomics and elaborates on applications in nutrition and
      health such as digestive health, allergy, diabetes and obesity, nutritional
      intervention and nutrient bioavailability. Proteomic developments, applications
      and potential in the field of nutrition have been specifically addressed in
      another review issued by our group.

PMID- 16600412
TI  - Mechanical properties of single living cells encapsulated in polyelectrolyte
      matrixes.
AB  - We have studied the mechanical properties of encapsulated Saccharomyces
      cerevisiae yeast cells by performing AFM force measurements. Single living cells
      have been coated through the alternate deposition of oppositely charged
      polyelectrolyte layers and mechanically trapped into a porous membrane. Coated
      and uncoated cells in presence/absence of bud scars, i.e. scars resulting from
      previous budding events, have been investigated. No significant differences
      between encapsulated and bare cells could be inferred from AFM topographs. On the
      other hand, investigation on the system elasticity through the acquisition and
      analysis of force curves allowed us to put in evidence the differences in the
      mechanical properties between the hybrid cell/polyelectrolyte system and the
      uncoated cells. Analysis of the curves contact region indicates that the
      polyelectrolyte coating increases the system rigidity. Quantitative evaluation of
      the cell rigidity through the Hertz-Sneddon model showed that coated cells are
      characterized by a Young's modulus higher than the value obtained for uncoated
      cells and similar to the value observed on the bud scar region of uncoated cells.

PMID- 16600413
TI  - CD4/CXCR4 co-expression allows productive HIV-1 infection in canine kidney MDCK
      cells.
AB  - The Madin-Darby canine kidney (MDCK) cell line has become the prototypic cell
      type for studying the mechanisms involved in viral glycoproteins transport and
      viral assembly in polarized cells. This cell line has been used in our
      laboratories for studying human immunodeficiency virus (HIV-1), despite the fact
      that MDCK cells cannot be infected by HIV. In transfected MDCK cells, HIV-1
      glycoproteins are specifically transported to the basolateral cell surface where
      viral budding also mostly occurs. However, this model is of limited use when
      viral propagation, infection of most cells, or larger production of virions, is
      needed. The initial objective of this work was thus to establish an MDCK-derived
      cell line that could be productively infected by HIV-1, in order to pursue our
      studies on the polarization of viral budding. Expression of both receptor and co
      receptor for T-tropic strains of the virus showed that canine cells are rendered
      permissive once virus binding and entry is allowed. In addition, a reduced
      infectivity of the viral particles released from the basolateral surface was
      observed. This observation most likely reflects the interference mediated by CD4
      molecules that accumulate at the basolateral domain. Accordingly, this effect was
      largely prevented when using viruses that down-regulate cell surface CD4 by
      expression of both viral accessory proteins Vpu and Nef. This is a further
      evidence that the function of different viral proteins depends of the site of
      viral budding, which is itself determined by the presence of targeting signal(s)
      harbored by viral envelope glycoproteins.

PMID- 16600414
TI  - A single transplantation of the islets can produce glycemic stability and
      reduction of basal insulin requirement.
AB  - We investigated glycemic stability and insulin requirement 1 month after a single
      transplantation of the islets from non-heart-beating donors or a living donor.
      Overall blood glucose levels decreased immediately after transplantation. The M
      value and mean amplitude of glycemic excursions (MAGE) decreased significantly
      from 53.0 (range, 8.9-91.0) to 4.2 (0.6-8.8, P<0.05) and from 8.5 mM (4.8-11.7)
      to 3.3 mM (2.0-4.5, P<0.05), respectively. The values after transplantation were
      lower than the first quartile of 102 type 2 diabetic control patients. The
      estimated HbA1c level decreased significantly from 7.9% (5.7-10.9) to 5.4% (4.7
      5.9, P<0.05). The supplement of basal insulin decreased 43% from 0.31
      units/kg/day (0.16-0.37) to 0.18 units/kg/day (0-0.22, P<0.05), while that of
      stimulated insulin did not decrease significantly, from 0.28 units/kg/day (0.13
      0.51) to 0.21 units/kg/day (0-0.41). Thus, only one islet transplantation can be
      sufficient to attain metabolic stability, probably by effective supply of basal
      insulin secretion, sufficient to avoid life-threatening severe hypoglycemia and
      prevent or delay the progress of secondary complications of diabetes by
      decreasing the HbA1c level.

PMID- 16600415
TI  - The sequential changes in the fasting plasma glucose levels within normoglycemic
      range predict type 2 diabetes in healthy, young men.
AB  - AIMS: We assessed whether the increased sequential changes in the fasting plasma
      glucose level (FPG) that is still within the normoglycemic range could be a
      predictor for future diabetes. METHODS: A prospective cohort study was conducted
      with 5296 male employees, aged 31-44 years. A sequential change in the FPG level
      was defined as the first follow-up FPG level minus the baseline FPG level. The
      incident diabetes was assessed at annual examinations during the next 4.1 years.
      Cox proportional hazard analyses were performed. RESULTS: During the 21,575.5
      person-years follow-up among the 5,296 subjects, a total of 156 incident cases of
      type 2 diabetes occurred (116 cases among the 4,975 normoglycemic subjects and 40
      cases among the 321 subjects with impaired fasting glucose). An increase in the
      FPG level from the baseline to the first follow-up, although still within the
      normoglycemic range (FPG<100 mg/dl), significantly predicted future diabetes: the
      multivariate hazard ratios associated with the sequential changes in the FPG of <
      3, -3 to 3, 4-6, 7-9, and >9 mg/dl were 0.75, 1.00 (reference), 2.28, 3.28, and
      6.10, respectively (p for trend <0.001). CONCLUSIONS: The increase of the
      sequential changes in the FPG level that were within the normal glucose range was
      associated with a higher risk for developing diabetes. Thus, conducting
      assessment for the serial changes in the FPG level may help to identify the
      young, healthy, normoglycemic individuals at risk for type 2 diabetes.

PMID- 16600416
TI  - Increase of CD4+ CD25+ regulatory T-cells in the liver of patients with
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The immune response to tumor-specific antigens is typically
      unable to control the growth and spread of malignant cells. Accumulating evidence
      indicates that the suppressive effects of CD4+ CD25+ regulatory T-cells are at
      least partially responsible for the failure of immune-mediated elimination of
      tumor cells. METHODS: We have studied 25 patients with hepatocellular carcinoma
      (HCC). The liver tissues with HCC were separated into the marginal region of
      tumor (peri-tumor region) and the non-tumor region distant from the tumor. CD4+
      CD25+ T-cells were quantified in the blood and the liver by flow cytometry and
      immunohistochemistry, and their effect on T-cell proliferation and activation was
      determined. RESULTS: We found a significant increase in both the proportion and
      absolute numbers of CD4+ CD25+ T-cells in the peri-tumor regions, but not in
      unaffected areas (9.5 +/- 4.5 vs. 4.6 +/- 2.8%, P = 0.011). CD4+ CD25+ T-cells
      isolated from peri-tumor regions displayed phenotype markers characteristic of
      regulatory T-cells, and expressed Foxp3 mRNA. CD8+ T-cells in peri-tumor regions
      were inversely proportional to CD4+ CD25+ T-cells in the same region (P < 0.001).
      Moreover, isolated CD4+ CD25+ T-cells inhibited autologous CD8+ T-cell
      proliferation. CONCLUSIONS: Our results suggest that CD4+ CD25+ T-cells in the
      marginal region of HCC may play a critical role in controlling CD8+ cytotoxic T
      cell activity and, thereby, contribute to the progression of HCC.

PMID- 16600417
TI  - Interleukin-6 is a key mediator of the hepatoprotective and pro-proliferative
      effects of ischaemic preconditioning in mice.
AB  - BACKGROUND/AIMS: The biological effects of ischaemic preconditioning include NF
      kappaB activation, increased TNF synthesis, stimulation of cell cycle entry and
      hepatoprotection against ischaemia-reperfusion (IR) injury. Low dose TNF
      initiates the priming phase of liver regeneration via NF-kappaB and IL-6. To
      determine whether (1) IL-6 is released during preconditioning and confers
      protection against hepatic IR injury, and (2) IL-6 could mediate the biological
      effects of preconditioning. METHODS: Wildtype (wt) and TNF-/- C57BL6 mice were
      subjected to 90 min partial hepatic ischaemia and 2-44 h reperfusion with or
      without prior 10 min ischaemic preconditioning. To restitute liver injury, TNF-/-
      mice were administered murine TNF 5 microg/kg iv 1 min prior to IR. Murine
      recombinant IL-6 (500 ng/kg iv) was administered 30 min prior to IR, either to wt
      mice or to TNF-/--repleted mice; in the latter case, 1 min before
      preconditioning. RESULTS: In wt mice, IL-6 attenuated hepatic IR injury and
      stimulated cell cycle entry. IR injury in TNF-repleted TNF-/- mice was not
      ameliorated by preconditioning. However, prior IL-6 administration conferred
      hepatoprotection (IL-6/preconditioned: 349+/-169 U/L vs vehicle/preconditioned:
      1250+/-608 U/L, P<0.01). CONCLUSIONS: IL-6 is one likely mediator of the
      hepatoprotective and pro-proliferative effects of ischaemic preconditioning.

PMID- 16600418
TI  - Disease management and health care reforms in Germany - does more competition
      lead to less solidarity?
AB  - Up to the 1990s German health care legislation was dominated by measures
      regulating the supply side. Measures, such as budgets, aimed at volume control
      and sought to confine the increase of health care spending to the growth of the
      national income. To curb costs more effectively, competitive elements were
      introduced in the 1990s with free choice of sickness funds (open enrollment). To
      balance competition and solidarity, a risk compensation scheme (RCS) was
      implemented two years prior to open enrollment. Since then, balancing competition
      and solidarity has been a key feature of all consecutive health care reforms. The
      implementation of disease management programs in the statutory health insurance
      (SHI) served the dual purpose to promote quality of care and to foster
      competition. Preliminary experiences suggest, that the aligning of disease
      management programs with a RCS can greatly aid its implementation and benefit
      solidarity and competition.

PMID- 16600419
TI  - Drug-eluting stents: beyond the hyperbole.
AB  - Drug-eluting stents (DES) promised to reduce the clinical and economic cost of
      failed bare metal stents (BMS) by locally delivering a therapeutic agent to the
      injured artery, reducing or eliminating the development of neointimal hyperplasia
      and reducing the need for repeat interventions to re-open the obstructed artery.
      Data from initial large-scale, comparable, U.S. pivotal trials of the first two
      DES to reach the American market, CYPHER from J&J using the drug rapamycin
      (sirolimus) and TAXUS from Boston Scientific using the drug paclitaxel (taxol),
      seemed to warrant the enthusiasm. By reducing the failure rate of BMS by about 4
      fold, DES have changed clinical practice, reduced the rate of coronary bypass
      surgery, had a significant economic impact, and triggered extensive research in
      the areas of stent design, restenosis biology, polymeric drug-delivery and local
      pharmacology and toxicology.

PMID- 16600420
TI  - A multi-objective optimization framework for surfactant-enhanced remediation of
      DNAPL contaminations.
AB  - The occurrence of Dense Non-Aqueous Phase Liquid (DNAPL) contaminations in the
      subsurface is a threat for drinkwater resources in the western world. Surfactant
      Enhanced Aquifer Remediation (SEAR) is widely considered as one of the most
      promising techniques to remediate DNAPL contaminations in-situ, be it with
      considerable additional costs compared to classical pump-and-treat remediations.
      A cost-effective design of the remediation set-up is therefore essential. In this
      work, a pilot SEAR test is executed at a DNAPL contaminated site in Belgium in
      order to collect data for the calibration of a multi-phase multi-component model.
      The calibrated model is used to assess a series of scenario-analyses for the full
      scale remediation of the site. The remediation variables that were varied were
      the injection and extraction rate, the injection and extraction duration, and the
      surfactant injection concentrations. A constrained multi-objective optimization
      of the model was applied to obtain a Pareto set of optimal remediation strategies
      with different weights for the two objectives of the remediation: (i) the maximal
      removal of DNAPL and (ii) a total minimal cost. These Pareto curves can help
      decision makers to select an optimal remediation strategy in terms of cost and
      remediation efficiency. The Pareto front shows a considerable trade-off between
      the total remediation cost and the removed DNAPL mass.

PMID- 16600421
TI  - Simulation of solute transport across low-permeability barrier walls.
AB  - Low-permeability, non-reactive barrier walls are often used to contain
      contaminants in an aquifer. Rates of solute transport through such barriers are
      typically many orders of magnitude slower than rates through the aquifer.
      Nevertheless, the success of remedial actions may be sensitive to these low rates
      of transport. Two numerical simulation methods for representing low-permeability
      barriers in a finite-difference groundwater-flow and transport model were tested.
      In the first method, the hydraulic properties of the barrier were represented
      directly on grid cells and in the second method, the intercell hydraulic
      conductance values were adjusted to approximate the reduction in horizontal flow,
      allowing use of a coarser and computationally efficient grid. The alternative
      methods were tested and evaluated on the basis of hypothetical test problems and
      a field case involving tetrachloroethylene (PCE) contamination at a Superfund
      site in New Hampshire. For all cases, advective transport across the barrier was
      negligible, but preexisting numerical approaches to calculate dispersion yielded
      dispersive fluxes that were greater than expected. A transport model (MODFLOW
      GWT) was modified to (1) allow different dispersive and diffusive properties to
      be assigned to the barrier than the adjacent aquifer and (2) more accurately
      calculate dispersion from concentration gradients and solute fluxes near
      barriers. The new approach yields reasonable and accurate concentrations for the
      test cases.

PMID- 16600422
TI  - The area composita of adhering junctions connecting heart muscle cells of
      vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in
      the intercalated disk.
AB  - Using immunofluorescence histochemistry and immunoelectron microscopy on sections
      through myocardiac tissues of diverse mammalian (human, cow, rat, mouse) and fish
      species we show that both desmosomal and fascia adhaerens proteins identified by
      gel electrophoresis and immunoblot occur in the area composita, the by far major
      type of plaque-bearing junctions of the intercalated disks (IDs) connecting
      cardiomyocytes. Specifically, we demonstrate that desmoplakin and the other
      desmosomal proteins occur in these junctions, together with N-cadherin, cadherin
      11, alpha- and beta-catenin as well as vinculin, afadin and proteins p120(ctn),
      ARVCF, p0071, and ZO-1, suggestive of colocalization. We conclude that the
      predominant type of adhering junction present in IDs is a junction sui generis,
      termed area composita, that is characterized by an unusually high molecular
      complexity and an intimate association of molecules of both ensembles, the
      desmosomal one and the fascia adhaerens category. We discuss possible myocardium
      specific, complex-forming interactions between members of the two ensembles and
      the relevance of our findings for the formation and functioning of the heart and
      for the understanding of hereditary and other cardiomyopathies. We further
      propose to use this highly characteristic area composita ensemble of molecules as
      cardiomyocyte markers for the monitoring of cardiomyogenesis, cardiomyocyte
      regeneration and possible cardiomyocyte differentiation from mesenchymal stem
      cells.

PMID- 16600423
TI  - Compartmentalized PKA signaling events are required for synaptic tagging and
      capture during hippocampal late-phase long-term potentiation.
AB  - Synaptic plasticity, the activity-dependent change in the strength of neuronal
      connections, is a proposed cellular mechanism of memory storage that is
      critically regulated by protein kinases such as cAMP-dependent protein kinase
      (PKA). Despite the fact that a neuron contains thousands of synapses, the
      expression of synaptic plasticity can be specific to subsets of synapses. This is
      surprising because signal transduction pathways underlying synaptic plasticity
      involve diffusible second messenger molecules such as cAMP and diffusible
      proteins such as the catalytic subunit of PKA. One way in which this specificity
      can be achieved is by the localization of signal transduction molecules to
      specific subcellular domains. Spatial compartmentalization of PKA signaling is
      achieved via binding to A kinase-anchoring proteins (AKAPs). We report here that
      pharmacological inhibition of PKA anchoring impairs synaptically activated late
      phase long-term potentiation (L-LTP) in hippocampal slices. In contrast,
      potentiation that is induced by the pharmacological activation of the cAMP/PKA
      pathway, which can potentially affect all synapses within the neuron, is not
      impaired by inhibition of PKA anchoring. These results suggest that PKA anchoring
      may be particularly important for events that occur at the synapse during the
      induction of L-LTP, such as synaptic tagging and capture. Indeed, our results
      demonstrate that blocking PKA anchoring impairs synaptic tagging and capture.
      Thus our data highlight the idea that PKA anchoring may allow for specific
      populations of synapses to change in synaptic strength in the face of plasticity
      related transcription that is cell-wide.

PMID- 16600424
TI  - Phosphorylation of the p34(cdc2) target site on goldfish germinal vesicle lamin
      B3 before oocyte maturation.
AB  - The nuclear membranes surrounding fish and frog oocyte germinal vesicles (GVs)
      are supported by the lamina, an internal, mesh-like structure that consists of
      the protein lamin B3. The mechanisms by which lamin B3 is transported into GVs
      and is assembled to form the nuclear lamina are not well understood. In this
      study, we developed a heterogeneous microinjection system in which wild-type or
      mutated goldfish GV lamin B3 (GFLB3) was expressed in Escherichia coli,
      biotinylated, and microinjected into Xenopus oocytes. The localization of the
      biotinylated GFLB3 was visualized by fluorescence confocal microscopy. The
      results of these experiments indicated that the N-terminal domain plays important
      roles in both nuclear transport and assembly of lamin B3 to form the nuclear
      lamina. The N-terminal domain includes a major consensus phosphoacceptor site for
      the p34(cdc2) kinase at amino acid residue Ser-28. To investigate nuclear lamin
      phosphorylation, we generated a monoclonal antibody (C7B8D) against Ser-28
      phosphorylated GFLB3. Two-dimensional (2-D) electrophoresis of GV protein
      revealed two major spots of lamin B3 with different isoelectric points (5.9 and
      6.1). The C7B8D antibody recognized the pI-5.9 spot but not the pI-6.1 spot. The
      former spot disappeared when the native lamina was incubated with lambda phage
      protein phosphatase (lambda-PP), indicating that a portion of the lamin protein
      was already phosphorylated in the goldfish GV-stage oocytes. GFLB3 that had been
      microinjected into Xenopus oocytes was also phosphorylated in Xenopus GV lamina,
      as judged by Western blotting with C7B8D. Thus, lamin phosphorylation appears to
      occur prior to oocyte maturation in vivo in both these species. Taken together,
      our results suggest that the balance between phosphorylation by interphase lamin
      kinases and dephosphorylation by phosphatases regulates the conformational
      changes in the lamin B3 N-terminal head domain that in turn regulates the
      continual in vivo rearrangement and remodeling of the oocyte lamina.

PMID- 16600425
TI  - Leaf-specific suppression of deoxyhypusine synthase in Arabidopsis thaliana
      enhances growth without negative pleiotropic effects.
AB  - Deoxyhypusine synthase (DHS) mediates the first of two enzymatic reactions
      required for the post-translational activation of eukaryotic translation
      initiation factor 5A (eIF5A), which in turn is thought to facilitate translation
      of specific mRNAs. Analyses of GUS activity in transgenic Arabidopsis plants
      expressing the GUS reporter gene under regulation of the promoter for AtDHS
      revealed that the expression of DHS changes both spatially and temporally as
      development progresses. In particular, DHS is expressed not only in rosette
      leaves, but also in the anthers of developing flowers. To determine the role of
      DHS in leaves, transgenic plants in which DHS was selectively suppressed in
      rosettes of Arabidopsis plants were prepared. This was achieved by expressing
      AtDHS 3'-UTR cDNA as a transgene under regulation of the promoter for AtRbcS2, a
      gene encoding the small subunit of Rubisco. The dominant phenotypic traits of the
      DHS-suppressed plants proved to be a dramatic enhancement of both vegetative and
      reproductive growth. As well, the onset of leaf senescence in the DHS-suppressed
      plants was delayed by approximately 1 week, but there was no change in the timing
      of bolting. In addition, there was no evidence for the negative pleiotropic
      effects, including stunted reproductive growth and reduced seed yield, noted
      previously for transgenic plants in which DHS was constitutively suppressed. The
      results indicate that DHS plays a pivotal role in both growth and senescence.

PMID- 16600426
TI  - Comparative studies on pyrimidine metabolism in excised cotyledons of Pinus
      radiata during shoot formation in vitro.
AB  - Changes in the pattern of pyrimidine nucleotide metabolism were investigated in
      Pinus radiata cotyledons cultured under shoot-forming (SF; +N(6)-benzyladenine)
      and non-shoot-forming (NSF, -N(6)-benzyladenine) conditions, as well as in
      cotyledons unresponsive (OLD) to N(6)-benzyladenine. This was carried out by
      following the metabolic fate of externally supplied (14)C-labeled orotic acid,
      intermediate of the de novo pathway, and (14)C-labeled uridine and uracil,
      substrates of the salvage pathway. Nucleic acid synthesis was also investigated
      by following the metabolic fate of (14)C-labeled thymidine during shoot bud
      formation and development. The de novo synthesis of pyrimidine nucleotides was
      operative under both SF and NSF conditions, and the activity of orotate
      phosphoribosyltransferase (OPRT), a key enzyme of the de novo pathway, was higher
      in SF tissue. Utilization of both uridine and uracil for nucleotide and nucleic
      acid synthesis clearly indicated that the salvage pathway of pyrimidine
      metabolism is also operative during shoot organogenesis. In general, uridine was
      a better substrate for the synthesis of salvage products than uracil, possibly
      due to the higher activity of uridine kinase (UK), compared to uracil
      phosphoribosyltransferase (UPRT). Incorporation of uridine into the nucleic acid
      fraction of OLD cotyledons was lower than that observed for their responsive (day
      0) counterparts. Similarly, uracil utilization for nucleic acid synthesis was
      lower in NSF cotyledons, compared to that observed for SF tissue after 10 days in
      culture. This difference was ascribed to higher UPRT activity measured in the
      latter. Thus, there was an apparent difference in the utilization of nucleotides
      derived from uracil and uridine for nucleotide synthesis. The increased ability
      to produce pyrimidine nucleotides via the salvage pathway during shoot bud
      formation may be required in support of nucleic acid synthesis occurring during
      the process. Studies on thymidine metabolism confirmed this notion.

PMID- 16600427
TI  - A cluster of deep bacterial infections following eye surgery associated with
      construction dust.
AB  - SUMMARY: Three cases of serious eye infection (two endophthalmitis, one orbital
      cellulitis; two caused by Staphylococcus aureus, one caused by viridans
      streptococci) occurred shortly after surgery (two cataracts, one retinal
      detachment repair) within two weeks. There had been construction work adjacent to
      the theatres during this time, and fine dust was found on horizontal surfaces.
      Further surgery was cancelled, the construction work was completed and theatres
      were cleaned before recommencing with no further infections. Following a review
      of factors that may be involved in the pathogenesis of endophthalmitis, it is
      proposed that the mechanism of infection in these cases may have been due to the
      presence of foreign material enhancing the pathogenicity of the small numbers of
      organisms often found in intra-ocular fluids during surgery. This hypothesis
      could be tested in experimental models of endophthalmitis.

PMID- 16600428
TI  - Risk factors for Staphylococcus aureus nasal carriage in residents of three
      nursing homes in Germany.
AB  - The prevalence of Staphylococcus aureus nasal carriage in three nursing homes
      (N=500) was 36.6%. No meticillin-resistant S. aureus (MRSA) was detected. The
      following significant risk factors for S. aureus nasal carriage were identified:
      vascular cognitive impairment [odds ratio (OR)=0.31]; diabetes mellitus
      (OR=1.82); hypertension (OR=0.30); chronic obstructive pulmonary disease
      (OR=1.86); stroke (OR=3.31); antibiotic therapy within the previous three months
      (OR=2.10); and level 2 care (defined as highly dependent, needing help in
      activities of daily living for up to 4h/day) (OR=1.97). Compared with other
      countries, the prevalence of MRSA nasal carriage in residents of German nursing
      homes is low.

PMID- 16600429
TI  - Ethanol disinfection of plastic-adherent micro-organisms.
AB  - This study investigated the bactericidal effect of ethanol/water (70:30 vol:vol)
      against plastic-adherent organisms that commonly cause line infections. The
      experiments were performed in polycarbonate wells and all incubations were at 37
      degrees C. Bacteria in broth were inoculated into wells and incubated (16, 40 and
      72 h) before washing to remove non-adherent organisms and exposure to
      ethanol/water. Wells were then re-incubated with broth to detect surviving
      bacteria. All organisms incubated for 16 h were killed by 1h of exposure to 70%
      ethanol. After incubation for 40 h, 4h of exposure to ethanol was required to
      kill two strains of Candida albicans. Likewise, one of three of both Klebsiella
      pneumoniae and Pseudomonas aeruginosa, incubated for 72 h, showed growth after 1h
      of exposure to 70% ethanol but not after 4h of exposure. These results suggest
      that in contrast to log phase organisms, which are killed by ethanol/water
      solutions in seconds, plastic-adherent organisms are more resistant to the
      bactericidal activity of ethanol.

PMID- 16600430
TI  - Nanocrystalline silver dressings as an efficient anti-MRSA barrier: not a new
      solution to an increasing problem?

PMID- 16600431
TI  - Thymidine-dependent meticillin-resistant Staphylococcus aureus: a potentially
      unrecognized reservoir of MRSA in hospital patients?

PMID- 16600432
TI  - Disinfection of fabrics and carpets artificially contaminated with calicivirus:
      relevance in institutional and healthcare centres.
AB  - Fabrics and carpets are used widely as surface coverings or linens in healthcare
      settings and are prone to contamination with infectious agents such as
      noroviruses (NoVs). Laundering, water cleaning and vacuuming are considered to be
      adequate for routine cleaning of these materials, but no standard procedure for
      their disinfection is available in case of contamination. Testing disinfectants
      for their efficacy against NoVs is difficult because these viruses cannot be
      cultivated in vitro. Therefore, feline calicivirus (FCV) has gained acceptance as
      a surrogate model for NoVs in disinfectant efficacy testing. The present study
      evaluated five disinfectants against FCV on various fabrics or carpets. FCV was
      dried on fabrics and carpets, followed by treatment with a given disinfectant for
      a defined contact time of 1, 5 or 10 min. The surviving virus was then eluted and
      titrated in Crandell-Reese feline kidney cells to determine virus inactivation. A
      disinfectant was considered to be effective if it inactivated at least 99% of the
      applied virus. Metricide, an activated dialdehyde-based product, was found to be
      the most effective disinfectant on all types of fabric and carpet, inactivating
      more than 99.99% of the virus in 1-10 min. In general, effectiveness of
      disinfectants increased with an increase in exposure time from 1 to 10 min. The
      disinfection of carpets was more difficult than the disinfection of fabrics; 100%
      polyester was the least amenable to disinfection. Only Metricide and Microbac-II
      (a phenolic compound) were able to inactivate 99% of FCV on 100% polyester. In
      summary, activated dialdehyde was found to be uniformly active against FCV on all
      types of material tested.

PMID- 16600433
TI  - Incidence of hospital-acquired infections in Italian long-term-care facilities: a
      prospective six-month surveillance.
AB  - This study presents results from a six-month prospective surveillance of hospital
      acquired infections in four Italian long-term-care facilities (LTCFs). Eight
      hundred and fifty-nine patients were enrolled and 21 503 person-days were
      observed. Two hundred and fifty-four hospital-acquired infections (HAIs) occurred
      in 188 patients. The overall infection rate was 11.8 per 1000 person-days. The
      most frequent infections were urinary tract infections (3.2 per 1000 person
      days), lower respiratory tract infections (2.7 per 1000 person-days) and skin
      infections (2.5 per 1000 person-days). Risks related to HAI in a multi-variate
      regression model were: length of stay >or=28 days [odds ratio (OR) 3.5, 95%
      confidence intervals (CI) 2.4-5.0]; presence of a device (OR 2.0, 95%CI 1.3-3.0);
      Norton scale <12 (OR 1.8, 95%CI 1.2-2.6); and being bedridden (OR 1.7, 95%CI 1.08
      2.6). The presence of HAI increased the median length of stay (31 days vs 20
      days, P<0.01) without a significant influence on fatal outcome (OR 1.4, 95%CI 0.7
      2.7).

PMID- 16600434
TI  - Neuronal electrical high frequency stimulation enhances GABA outflow from human
      neocortical slices.
AB  - Electrical high frequency stimulation of the globus pallidus internus or the
      subthalamic nucleus has beneficial motor effects in advanced Parkinson's disease.
      The mechanisms underlying these clinical results remain, however, unclear. From
      previous studies it is proposed that the gamma-aminobutyric acid (GABA) system is
      involved in the effectiveness of electrical high frequency stimulation. In these
      experiments, human neocortical slices were stimulated electrically (130 Hz) in
      vitro, and GABA outflow was measured after o-phthaldialdehyde sulphite
      derivatization using HPLC with electrochemical detection. Our results could
      demonstrate that high frequency stimulation (HFS) significantly increased basal
      GABA outflow in the presence of submaximal concentrations of the voltage-gated
      sodium channel opener veratridine. This effect could be abolished by the GABA
      antagonists bicuculline or picrotoxin. These results suggest that HFS has an
      activating effect on GABAergic neuronal terminals in human neocortical slices,
      depending on sodium and chloride influx. Since GABA plays a role in CNS disorders
      of basal ganglia, anxiety and epilepsy, its neocortical modulation by HFS may be
      (patho)physiologically relevant.

PMID- 16600435
TI  - The magnetism responsive gene Ntan1 in mouse brain.
AB  - We have previously identified Ntan1 as a magnetism response gene by differential
      display screening in cultured rat hippocampal neurons. Ntan1 mRNA was
      ubiquitously expressed in all the mouse tissues examined but relatively abundant
      in brain, retina and testis. Ntan1 mRNA expression was detectable in the
      embryonic 12-day mouse brain and gradually increased with ageing. In situ
      hybridization analysis showed high localization of Ntan1 mRNA in pyramidal cell
      layer of CA region and granular cell layer of dentate gyrus in the hippocampus,
      and Purkinje and granular cell layers in the cerebellum, respectively. Ntan1 mRNA
      expression was significantly increased about two-fold 12 h after brief exposure
      for 15 min to magnetism at 100 mT with a gradual decrease thereafter in cultured
      mouse hippocampal neurons. When embryonic 12-day-old or newborn mice were
      successively exposed to magnetic fields at 100 mT for 2 h, four times per day
      until the postnatal seventh day, Ntan1 mRNA was significantly increased about 1.5
      2-fold in the hippocampus in vivo. The mice exposed to magnetic fields under the
      same condition showed significantly decreased locomotor activity. These results
      suggest that magnetic exposure affects higher order neural functions through
      modulation of genes expression.

PMID- 16600436
TI  - Muscarinic receptor-mediated GTP-Eu binding in the hippocampus and prefrontal
      cortex is correlated with spatial memory impairment in aged rats.
AB  - The present study examined muscarinic receptor/G-protein coupling in the
      hippocampus and the prefrontal cortex of young and aged Long-Evans rats
      characterized for spatial learning ability in the Morris water maze. In a highly
      sensitive time-resolved fluorometry GTP-Eu binding assay, muscarinic-mediated GTP
      Eu binding was severely blunted in hippocampus (-32%) and prefrontal cortex (
      34%) as a consequence of aging. Furthermore, the magnitude of decreased
      muscarinic-mediated GTP-Eu binding was significantly correlated with the severity
      of spatial learning impairment in hippocampus and prefrontal cortex of aged rats
      and was specifically decreased in the subset of aged rats that were spatial
      learning impaired when compared to the aged unimpaired and the young rats.
      Western blot data indicated a preservation of the membrane-bound M1 receptor and
      the Galphaq/11 protein in both brain regions. These data demonstrate that
      muscarinic signaling is severely impaired as a consequence of normal aging in a
      manner that is closely associated with age-related cognitive decline.

PMID- 16600437
TI  - Peripheral T cells overexpress MIP-1alpha to enhance its transendothelial
      migration in Alzheimer's disease.
AB  - It is unclear how circulating T cells cross the blood-brain barrier (BBB) and
      participate in the inflammation process in Alzheimer's disease (AD). Here we
      showed significantly higher macrophage inflammatory protein-1alpha (MIP-1alpha)
      expression in peripheral T lymphocytes of AD patients than age-matched controls.
      T cells crossing of the human brain microvascular endothelial cells (HBMECs)
      which constitute the BBB, were almost completely abrogated by anti-MIP-1alpha
      antibody. MIP-1alpha induced the expression of CCR5, a potential MIP-1alpha
      receptor, on HBMECs. HBMECs tranfected with CCR5 resulted in increased T cells
      transendothelial migration. CCR5 antagonist (2D7 mAb) blocked the T cells
      transmigration. The MIP-1alpha-CCR5 interaction promoted T cells transendothelial
      migration via ROCK (Rho kinase). Furthermore, Abeta injection into rats'
      hippocampus induced MIP-1alpha overexpression accompanied with increased T
      lymphocytes occurrence in the brain cortex and this enhanced T cells entry was
      effectively blocked by anti-MIP-1alpha antibody. These data are the first to
      suggest that the interaction between MIP-1alpha overexpressed by T cells and CCR5
      on HBMECs is involved in AD patients' T cells migrating from blood to brain.

PMID- 16600438
TI  - Synthesis, stereochemistry, and antimicrobial evaluation of substituted piperidin
      4-one oxime ethers.
AB  - In a wide search program toward new and efficient antimicrobial agents, a series
      of substituted piperidin-4-one oxime ethers (5a-5k) was synthesized and tested
      for their in vitro antibacterial and antifungal activities. Also, the structures
      of these oxime ethers and their relative stereochemistries have been investigated
      by nuclear magnetic resonance spectroscopy. In all the oxime ethers synthesized,
      the orientation of the N-O bond of the oxime ether moiety syn to C-5 (E-isomer)
      was deduced based on (1)H NMR and (13)C NMR spectra. It was found that the
      sterically less hindered compounds, either C-3 (H) and C-5 (H)- or C-3 (Me) and C
      5 (H) -substituted ones 5a, 5c, 5d, 5f, 5g, 5i and 5j prefer chair conformation,
      whereas the sterically more hindered C-3 (Me) and C-5 (Me) -substituted ones 5b,
      5e, 5h, and 5k prefer twist-boat conformation. Among the oxime ethers tested,
      1,3,5-trimethyl-2,6-diphenylpiperidin-4-one O-(2-chlorophenylmethyl)oxime (5h)
      exhibited good antibacterial property against Bacillus subtilis, with minimum
      inhibitory concentration (MIC) closer to that of reference drug, streptomycin.
      Compounds, 1,3-dimethyl-2,6-diphenylpiperidin-4-one O-(2-chlorophenylmethyl)oxime
      (5g) and 1,3-dimethyl-2,6-diphenylpiperidin-4-one O-(2-bromophenylmethyl)oxime
      (5j) showed potent antifungal activity against Aspergillus flavus and Candida-51,
      respectively. The later compound 5j is more active than the reference drug while
      the activity of the former one 5g is similar to that of the reference drug,
      amphotericin B in terms of MIC. The present results may be used as key steps for
      the construction of novel chemical entities with better pharmacological profiles
      than standard drugs.

PMID- 16600439
TI  - Synthesis, anticonvulsant activity and 5-HT1A, 5-HT2A receptor affinity of new N
      [(4-arylpiperazin-1-yl)-alkyl] derivatives of 2-azaspiro[4.4]nonane and
      [4.5]decane-1,3-dione.
AB  - The synthesis, physicochemical and pharmacological properties of new N-[(4
      arylpiperazin-1-yl)-alkyl]-2-azaspiro[4.4]nonane- (8a-c, 10a-d) and [4.5]decane
      1,3-dione (9a-c, 11a-d) derivatives were described. The antiepileptic effects of
      those compounds were examined by a maximal electroshock (MES) and a
      pentylenetetrazole (sc. PTZ) tests, and their neurotoxicity was determined using
      a rota-rod test. Compounds 8c, 9c, 10c, d, 11c, d with a CF(3) group at the 3
      position of the 4-arylpiperazine fragment exhibited anti-seizure properties in
      the MES model; in contrast, their 2-CH(3) and 2-OCH(3) analogues were inactive in
      both the tests used. Moreover, since the investigated compounds belong to the
      class of long-chain arylpiperazines, their serotonin 5-HT(1A) and 5-HT(2A)
      receptor affinity was determined. The relationship between the length of alkylene
      spacer and 5-HT(1A)/5-HT(2A) receptor activity was observed. Compounds with an
      ethylene and a propylene bridge (10a-d and 11a-d) were 3-80-fold more potent
      (K(i) ranged from 3.1 to 94 nM for 5-HT(1A) and 32-465 nM for 5-HT(2A)) than
      their methylene analogues (8a-c and 9a-c; K(i) ranged from 81 to 370 nM for 5
      HT(1A) and 126-1370 nM for 5-HT(2A)). The highest 5-HT(1A) receptor affinity was
      displayed by 2-OCH(3) and 3-CF(3) phenyl derivatives (10b, 11b: K(i)=6.8 and 5.7
      nM, respectively, and 10c, 11c: K(i)=6.0 and 3.1 nM, respectively), while in the
      case of 5-HT(2A) receptor the highest affinity was observed for the 3-CF(3)
      phenyl derivatives 10c, d, 11c, d (K(i) ranged from 32 to 86 nM).

PMID- 16600440
TI  - Protection capability of recombinant plasmid DNA vaccine containing VP2 gene of
      very virulent infectious bursal disease virus in chickens adjuvanted with CpG
      oligodeoxynucleotide.
AB  - In the present study the efficacy of recombinant plasmids DNA vaccine encoding
      VP2 gene of very virulent strain of infectious bursal disease virus (vvIBDV)
      isolated from Pakistan was investigated with or without coadministration of
      cytocine-phosphate-guanine oligodeoxynucleotide (CpG ODN) to protect the chickens
      against the disease. VP2 gene of vvIBDV was successfully amplified by reverse
      transcription-polymerase chain reaction (RT-PCR) and was cloned into eukaryotic
      expression plasmid vector, which consisted of human cytomegalovirus (HCMV)
      immediate early enhancer and promoter, adenopartite leader sequences and SV-40
      polyadenylation signal, and this was designated as pRc-VP2. Seven-day-old
      maternal antibodies free chickens were intramuscularly injected with 500 microg
      of pRc-VP2 with or without CpG ODN twice at 1-week interval. At the age of 21
      days the broiler chickens were challenged with 10(5) EID(50) of homologous strain
      of IBDV and observed for 14 days post-challenge. Immunization with pRc-VP2 plus
      CpG ODN conferred protection in 93% of the chickens as evidenced by the absence
      of clinical signs, atrophy of bursa of Fabricius (BF) and mortality followed by
      the group vaccinated with attenuated IBD vaccine and boosted with killed oil
      based IBDV vaccine, which conferred 90% protection. The protection of chickens
      injected with pRc-VP2 alone was 67% where as only 20% of the chickens in the
      negative control group were protected. However, enzyme-linked immunosorbent assay
      (ELISA) antibody titre in the group vaccinated with pRc-VP2 plus CpG ODN were
      significantly higher (P<0.05) than the group vaccinated with pRc-VP2 alone as
      well as the group vaccinated with commercial attenuated IBDV vaccine boosted with
      commercial oil adjuvanted killed IBDV vaccine. Responsiveness to a mitogenic
      lectin, phytoheamagglutinin-P was significantly reduced in group immunized with
      conventional vaccines (live boosted with killed) as compared to all the other
      groups (P<0.05). The results revealed that co-administration of recombinant
      plasmids with CpG ODN could protect chickens efficiently from IBDV challenge.

PMID- 16600441
TI  - Elastic liposomes mediated transcutaneous immunization against Hepatitis B.
AB  - Transcutaneous immunization presents a major challenge due to poor permeability
      of antigens through the skin barrier. To overcome this limitation ultradeformable
      lipid vesicles, the elastic liposomes, could be a better module for
      transcutaneous delivery of these proteinaceous antigens. In the present
      investigation Hepatitis B surface antigen (HBsAg)-loaded elastic liposomes were
      utilized as a mode for enhanced immunity against the antigen. Elastic liposomes
      were prepared by conventional rotary evaporation method and characterized for
      various parameters such as vesicles shape and surface morphology, size and size
      distribution, entrapment efficiency, elasticity, turbidity, stability and in
      vitro release pattern. Ex vivo cellular uptake and fluorescence studies were also
      conducted. In vivo studies were performed by measuring the immune response
      elicited by topically applied HBsAg-loaded elastic liposomes and compared to the
      intramuscularly administered alum-adsorbed HBsAg solution, topically applied
      plain HBsAg solution and physical mixture of HBsAg and elastic liposomes. Results
      indicate that transcutaneous immunization via elastic liposomes induces robust
      systemic and mucosal antibody response against HBsAg as compared to other
      formulations. The fluorescence microscopy results suggest prominent skin
      permeation and biodistribution, demonstrating efficient delivery of antigens to
      the immunocompetent Langerhans cells (LC) and lymphatics. The elastic liposomal
      formulation provides higher entrapment efficiency, enhanced penetration and
      effective immunoadjuvant property justifying its potential for improved vaccine
      delivery.

PMID- 16600442
TI  - Immunogenicity and efficacy of an in-house developed cell-culture derived
      veterinarian rabies vaccine.
AB  - The efficiency of an inactivated tissue culture rabies vaccine produced on BHK-21
      cells, according to an in-house developed process, was evaluated and compared to
      a commercial cell-tissue culture vaccine (Rabisin). Fifteen experimental dogs
      from local common breed were duly conditioned during a quarantine period, then
      vaccinated via the subcutaneous route with 1 ml of either the tissue culture
      vaccine developed in-house or the commercial vaccine Rabisin. The immune response
      of each dog was monitored for 162 days. Serum-neutralizing antibodies titers to
      rabies virus were determined by the rapid fluorescent focus inhibition test
      (RFFIT) which confirmed the strong response of dogs to both vaccines except one
      dog in the Rabisin group. The dogs were then challenged in the masseter muscle
      with a rabies street virus of canine origin. All vaccinated dogs except the
      single dog in the Rabisin group that failed to respond to the vaccine, survived
      the challenge. In contrast, 80% of animals in the control non-vaccinated group,
      developed rabies and died. A field vaccine trial was also conducted: 1,000 local
      dogs living in field conditions received one subcutaneous dose of the locally
      developed vaccine. Serum neutralizing antibody titers to rabies virus was
      determined by RFFIT at days 0, 60 and 360. Mean rabies neutralizing antibody
      titers were equal to 0.786, 3.73 and 1.55 IU/ml, respectively. The percentage of
      dogs with a neutralizing rabies antibody titer higher than the 0.5 IU/ml mandated
      WHO threshold, was 30%, 91.4% and 87.5% at day 0, 2 months and 1 year post
      vaccination, respectively. These data demonstrate the efficiency of the in-house
      developed vaccine produced on BHK-21 cells in both experimental and field
      conditions and support its use in dog mass vaccination campaigns.

PMID- 16600443
TI  - A short report on highlights of worldwide development of RIX4414: a Singaporean
      experience.
AB  - In Singapore, we conducted a phase II randomized, double-blind, placebo
      controlled dose ranging study using an attenuated human rotavirus vaccine,
      RIX4414. Altogether, 2464 healthy infants were recruited. Two oral doses of
      vaccine at 104.7, 105.2 or 106.1 ffu or placebo were administered with routine
      immunizations at 3 and 4 months of age. Seroconversion and 'vaccine take' in the
      vaccine groups 1-month post dose 2 varied from 76 to 91% and 98 to 100%
      respectively. Vaccine was well tolerated and did not interfere with response of
      concomitantly administered vaccines.

PMID- 16600444
TI  - Intranasal immunisation with conjugate vaccine protects mice from systemic and
      respiratory tract infection with Pseudomonas aeruginosa.
AB  - We tested intranasal application of anti-Pseudomonas conjugate vaccine in mice.
      Comparison of immunisation via the intra-muscular versus intranasal routes showed
      the induction of equivalent levels of specific serum IgG and IgG subclasses
      antibodies if cholera toxin was used as an adjuvant. In contrast, secretion of
      specific mucosal IgA antibodies in the upper respiratory tract was only observed
      after intranasal immunisation together with adjuvant. Systemic and mucosal
      immunity was also established via the intranasal route when CpG-containing
      oligonucleotides were used as adjuvant. The functionality of intranasally induced
      antibodies was proven in vitro by opsonophagocytosis and in vivo using the burn
      wound sepsis and intra-tracheal lung infection models. These results demonstrate
      the feasibility of intranasal immunisation against P. aeruginosa with conjugate
      vaccine.

PMID- 16600445
TI  - Influenza vaccination in severely multiply handicapped persons/children.
AB  - BACKGROUND: Many reports about the preventative effects of inactivated influenza
      vaccine have been published, targeting persons with underlying medical
      conditions. However, the effectiveness for severely multiply handicapped
      persons/children (SMHPs) is not yet well established. METHODS: The study group
      consisted of 79 SMHPs (36 males and 43 females, aged 18-66 years), with long-term
      hospitalization in Niigata National Hospital. We compared serum antibody
      responses before and after two-doses vaccination. RESULTS: Before vaccination for
      the 2004-2005 season, SMHPs showed continuously high HAI titer in A/New
      Caledonia/20/99(H1N1)-strain from March to October in 2004. The seroprotection
      rates were increased after the first dose, but no remarkable change was seen
      after the second dose in all three strains. Subjects less than 30 years old (< or
      = 29 group) had a high antibody titers against all three strains compared with
      subjects aged >40 years old. On the other hand, in the seroconversion rates,
      there were no significant differences in age, gender, and severity of symptoms.
      CONCLUSIONS: According to our study, SMHPs are low responders except < or = 29
      group and the influenza vaccine effectiveness is more affected by their age than
      severity of symptoms. We suggest a recommendation for influenza vaccination
      especially in SMHPs; inactivated influenza virus vaccine (one dose) should be
      performed during the previous fall. In addition, further studies are needed about
      chemoprophylaxis, which can prevent influenza outbreaks in SMHPs.

PMID- 16600446
TI  - Evaluation of a novel Vi conjugate vaccine in a murine model of salmonellosis.
AB  - Immunisation of BALB/c mice with a vaccine containing Vi polysaccharide
      conjugated to the Klebsiella pneumoniae outer membrane 40 kDa protein (rP40), in
      combination with Escherichia coli heat-labile toxin adjuvant (LT), elicited anti
      Vi IgG antibodies after administration using different routes. Testing of the
      immune serum in opsonisation assays demonstrated the specific enhancement of Vi
      positive bacterial uptake by cultured murine bone marrow derived macrophages.
      Intra-peritoneal challenge of mice immunised with the Vi-based vaccine elicited a
      degree of protection against virulent Vi+ Salmonella enterica serovar typhimurium
      (S. typhimurium). In contrast, Vi vaccination did not confer protection against
      oral challenge with virulent Vi-positive S. typhimurium or S. dublin.

PMID- 16600447
TI  - Challenges to microbicide introduction in South Africa.
AB  - Qualitative research was conducted in South Africa to determine perceptions about
      intra-vaginal microbicides in order to better understand the socioeconomic,
      cultural and structural contexts for the support of future introduction of this
      new HIV prevention method. Focus group discussions and in-depth interviews were
      conducted at community, health service, and policy levels of inquiry. The main
      study site was a black working class urban area close to Cape Town. "Desperation"
      in response to the HIV/AIDS epidemic, rape, sexual coercion and unplanned
      consensual sex emerged as major reasons to support microbicides, while concerns
      about the partial effectiveness of microbicide protection and its hypothetical
      nature elicited a more cautious approach. Other key findings included the
      likelihood that microbicides would be "mainstream", the possible impact on sexual
      practices and gender norms, issues of condom substitution/migration and potential
      avenues for education and distribution. We found that microbicides have the
      potential to meet diverse needs beyond that suggested by prior research. This
      included a desire for products that could protect against HIV infection following
      rape, sexual coercion and unplanned sex, and the finding that a wider range of
      people than previously suggested would potentially use microbicides. The
      challenge for microbicide introduction will be to develop products that can meet
      diverse needs not only in South Africa, but also in the broader global context.

PMID- 16600448
TI  - Hemispheric predominance assessment of phonology and semantics: a divided visual
      field experiment.
AB  - The aim of the present behavioural experiment was to evaluate the most
      lateralized among two phonological (phoneme vs. rhyme detection) and the most
      lateralized among two semantic ("living" vs. "edible" categorization) tasks,
      within the dominant hemisphere for language. The reason of addressing this
      question was a practical one: to evaluate the degree of the hemispheric
      lateralization for several language tasks, by using the divided visual
      presentation of stimuli, and then choose the most lateralized semantic and
      phonological for mapping language in patients by using fMRI in future studies.
      During the divided visual field experiment by using words (semantic tasks) and
      pseudo-words (phonological tasks) as stimuli, thirty-nine right-handed
      participants were examined. Our results have shown that all tasks were
      significantly left hemisphere lateralized. Furthermore, the rhyme was
      significantly more lateralized than phoneme detection and "living" was
      significantly more lateralized than "edible" categorization. The rhyme decision
      and "living" categorization will be used in future fMRI studies for assessing
      hemispheric predominance and cerebral substrate for semantics and phonology in
      patients. Our results also suggest that the characteristics of stimuli could
      influence the degree of the hemispheric lateralization (i.e., the emotional
      charge of stimuli for words and the position of the phoneme to be detected, for
      pseudo-words).

PMID- 16600449
TI  - Magnitude of cerebral asymmetry at rest: covariation with baseline cardiovascular
      activity.
AB  - The cerebral regulation of cardiovascular functioning varies along both a lateral
      and a longitudinal axis. The parasympathetic and sympathetic nervous systems are
      lateralized to the left and right cerebral hemispheres, respectively. Further,
      the frontal lobes are known to be inhibitory in nature, whereas the temporal
      lobes are excitatory. However, no systematic investigation has been conducted to
      determine the nature and strength of the relationship between the left and right
      frontal and temporal lobes in regulating cardiovascular activity. The present
      investigation sought to examine these relationships by testing the hypothesis
      that negative correlations would be found between baseline heart rate and blood
      pressure and asymmetry of alpha magnitude across the frontal lobes. Further,
      positive correlations were hypothesized to exist across the temporal lobes. A
      total of 20 women were asked to relax with their eyes closed while heart rate and
      blood pressure as well as quantitative electroencephalography data were obtained.
      The results indicated that, as hypothesized, significant negative correlations
      existed across the frontal lobes and significant positive correlations existed
      across the temporal lobes. The results provide further support for a division of
      responsibility between the left and right frontal and temporal lobes in the
      regulation of heart rate and blood pressure.

PMID- 16600450
TI  - Volumetric investigation of brain regions in patients with conversion disorder.
AB  - Preliminary evidence revealed a decrease of regional cerebral blood flow in the
      thalamus and basal ganglia contralateral to the deficit and suggested that
      hysterical conversion deficits might entail a functional disorder in
      striatothalamocortical circuits. However, there is no systematic structural
      magnetic resonance imaging (MRI) study in the literature in patients with
      conversion disorder (CD). Therefore, we aimed to perform structural MRI to
      evaluate the brain regions of interest in first applying patients with CD.
      Morphometric MRI was used to compare regional brain volumes in ten women with CD
      and same number of healthy comparison subjects. Intracranial volume (ICV), whole
      brain volume, gray and white matter volumes did not differ between the patient
      and control groups. Patients with CD had significantly smaller mean volumes of
      the left caudate nucleus, lentiform nucleus (p<0.01 for caudate nucleus and
      p<0.05 for lentiform nucleus) and right caudate nucleus and lentiform nucleus
      (p<0.05 for both structures). In patients, the right thalamus was significantly
      smaller, and the left thalamus rendered to be smaller compared to healthy
      controls. Age at onset showed a significant relation with left caudate, and a
      near-significant trend with right thalamus volumes. In conclusion, our findings
      suggest that patients with CD have significantly smaller mean volumes of the left
      and right basal ganglia and smaller right thalamus, with a trend toward to
      smaller left thalamus compared to healthy controls and that these findings
      provide novel constraints for a modern psychobiological theory of hysteria.

PMID- 16600451
TI  - Sertraline, escitalopram and tianeptine related abnormal movements but not with
      bupropion: a case report.
AB  - It is not scarce that patients experience various extrapyramidal symptoms (EPS)
      during antidepressant drug therapy. Thus, choice of an antidepressant drug in
      case of extrapyramidal side effects, at present, is a dilemma. Escitalopram,
      which is a recently marketed selective serotonin reuptake inhibitors (SSRI), has
      no such reputation. There is just one case reported for tianeptine that induced
      abnormal involuntary movements/extrapyramidal side effects. We would like to
      present a case that was successfully managed with bupropion which had developed
      EPS during 2 different SSRI (sertraline and escitalopram) and tianeptine therapy.

PMID- 16600452
TI  - Effect of carbamazepine on the single oral dose pharmacokinetics of perospirone
      and its active metabolite.
AB  - Perospirone is a serotonin 5-HT(2A) and dopamine D(2) receptor antagonist which
      originated in Japan. It has been shown that perospirone is metabolized to ID
      15036 mainly by CYP3A4 based on an in vitro study. To investigate the metabolism
      of perospirone in humans, the authors measured the concentration of perospirone
      and ID-15036 after a single oral dose of perospirone (8 mg) in 10 healthy male
      subjects, before and during coadministration of carbamazepine, known as a potent
      inducer of CYP3A4. Before carbamazepine coadministration, the peak plasma
      concentrations+/-SD of perospirone and ID-15036 were 4.0+/-4.3 and 11.7+/-7.1
      ng/ml, respectively. During carbamazepine coadministration, the concentration of
      perospirone was decreased below the detection limit, and that of ID-15036 was
      6.0+/-1.7 ng/ml. The concentrations of perospirone and ID-15036 were influenced
      significantly by the treatment with carbamazepine, and this was probably
      attributable to the induction of CYP3A4. This study provided an in vivo evidence
      of involvement of CYP3A4 in the metabolism of perospirone.

PMID- 16600453
TI  - A rare case of dependence on pemoline.
AB  - This is the first case to report about a patient dependent on the dopaminergic
      CNS-stimulant pemoline. Throughout the treatment of adult attention-deficit
      hyperactivity disorder (ADHD) with pemoline mental (e.g. craving, loss of
      control) and physical symptoms (e.g. tolerance, withdrawal symptoms) appeared
      that fulfill the DSM-IV or ICD-10 criteria for dependence on psychostimulants.
      However, the dependence was regarded not to be induced by pemoline itself because
      the patient was prone to irregular and reinforced intake of amphetamines since
      her adolescence. Therefore, this case confirms the experience that in the
      treatment of ADHD the high risk to develop a dependence on psychostimulants is
      combined with a history of stimulant abuse.

PMID- 16600454
TI  - Assessment of P wave duration and dispersion in Parkinson's disease.
AB  - Cardiovascular disorders such as decreased heart rate variability, orthostatic
      hypotension, and arrhythmias have been frequently observed in Parkinson's disease
      (PD) patients. In this study, authors measured P wave duration and dispersion in
      PD patients and controls. Twenty-three consecutive patients with idiopathic PD
      and sex-age matched 23 control subjects were included to the study. A 12-lead
      surface ECG was obtained from each participant. Maximum-minimum P wave duration
      and P wave dispersion (PWD) were measured in both groups. Maximum P wave duration
      was found to be higher in PD patients than controls (117+/-12 vs. 105+/-9 ms
      p=0.001). Minimum P wave duration was similar in PD patients and controls (64+/
      11 vs. 63+/-11 ms p=0.7). PWD in PD patients was also found to be higher than
      those of controls (53+/-11 vs. 43+/-10 ms p=0.0001). P wave duration and PWD did
      not significantly differ between PD patients taking anti-parkinsonian agents from
      those who were not (119+/-13 vs. 116+/-13 ms p=0.4 and 55+/-11 vs. 52+/-11 ms
      p=0.5, respectively). Moreover, when the PD patients taking anti-parkinsonian
      agents were excluded from the study, PD patients had still higher P wave duration
      and PWD compared to controls (119+/-11 vs. 105+/-9 ms p=0.004, 52+/-10 vs. 43+/
      10 ms p=0.009, respectively). In conclusion, we found that P wave duration and
      PWD were greater in PD patients compared to control subjects.

PMID- 16600455
TI  - Successful treatment of polydipsia, water intoxication, and delusional jealousy
      in an alcohol dependent patient with clozapine.
AB  - The beneficial effect of clozapine on polydipsia and water intoxication in
      patients with schizophrenia has been demonstrated many times. The authors report
      a successful clozapine treatment of polydipsia, intermittent water intoxication,
      and delusional jealousy of an alcoholic. This is a rare case of clozapine
      treatment of a non-schizophrenic patient affected by polydipsia.

PMID- 16600456
TI  - Effects of maternal separation on neuropeptide Y and calcitonin gene-related
      peptide in "depressed" Flinders Sensitive Line rats: a study of gene-environment
      interactions.
AB  - Interactions between genetic vulnerability to stress/depression and early life
      experience may play a crucial role in the pathogenesis of mood disorders. Here we
      explore this hypothesis by superimposing early life trauma in the form of
      maternal deprivation for 180 min per day from postnatal day 2 to 14 onto a
      genetic model of depression/susceptibility to depression, Flinders Sensitive Line
      (FSL) and their controls, Flinders Resistant Line (FRL) rats. We investigate
      effects on neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) like
      immunoreactivity (LI) in 10 brain regions as these neuropeptides are affected by
      antidepressants and are altered in cerebrospinal fluid of depressed patients. NPY
      LI was reduced while CGRP-LI was elevated in hippocampus and frontal cortex of
      "genetically depressed" FSL rats. The two peptides displayed a significant
      negative correlation in these regions that was strongest in the FSL strain.
      Maternal deprivation exacerbated the strain difference in hippocampal CGRP-LI,
      while it was without effect on NPY-LI. FSL rats had higher tissue concentration
      of both neuropeptides in periaqueductal grey and higher NPY-LI in
      caudate/putamen. Maternal deprivation selectively raised CGRP-LI in amygdala of
      the FRL control stain. Thus, in two brain regions implicated in the neurobiology
      of depression, hippocampus and frontal cortex, changes in CGRP-LI and NPY-LI were
      in opposite direction, and CGRP-LI appears to be more responsive to adverse
      experience. Our findings thus support the hypothesis that genetic disposition and
      developmental stress may contribute to the susceptibility to depression by
      exerting selective neuropeptide- and brain region-specific effects on adult
      neurobiology.

PMID- 16600457
TI  - Comparative effects of acute and subacute lycopene administration on chromosomal
      aberrations induced by cisplatin in male rats.
AB  - Lycopene is a natural carotenoid, free radical scavenger, and presents protective
      effects by inhibiting oxidative DNA damage. The objective of the current study
      was to investigate the cytogenetic effects of a single acute and four daily
      gavage administrations of lycopene, and to examine possible protective effects on
      chromosomal damage induced by the antitumor drug cisplatin (cDDP) in rat bone
      marrow cells. The animals were divided into treatment groups, with three lycopene
      doses in the acute treatment (2, 4, and 6 mg/kg b.w.), three lycopene doses in
      the subacute treatment (0.5, 1.0, and 1.5 mg/kg b.w.) with and without cDDP (5
      mg/kg b.w. i.p.), and respective controls. The results indicated that lycopene is
      neither cytotoxic nor clastogenic when compared with the negative controls
      (p>0.01). cDDP-treated animals submitted to acute and subacute treatments with
      different lycopene doses showed a significant reduction (p<0.01) in the number of
      abnormal metaphases when compared with the animals treated only with cDDP. The
      protective effects of lycopene on cDDP-induced chromosomal damage may be
      attributed to its antioxidant activity. These results suggest that this
      carotenoid may prove useful in reducing some of the toxic effects associated with
      certain classes of chemotherapeutic agents.

PMID- 16600458
TI  - Assessment of epoxidized soy bean oil (ESBO) migrating into foods: comparison
      with ESBO-like epoxy fatty acids in our normal diet.
AB  - Epoxidized soy bean oil (ESBO) was found to be toxic for rats, but the toxic
      constituent is unknown. It became an issue as the migration from the gaskets in
      the lids for jars into oily foods regularly far exceeds the European legal limit
      (overall migration limit and specific migration limit derived from the tolerable
      daily intake (TDI)). In the context of risk management it was of interest to
      determine the epoxidized fatty acids of ESBO in those foods of our normal diet
      which are expected to contain the highest concentrations, i.e., oxidized edible
      oils (including degraded frying oils), fried foods, bakery ware and roasted meat.
      The contribution of epoxy oleic acid from ESBO to our diet turned out to be
      negligible. If this acid were the toxic component in ESBO, the toxicological
      assessment would primarily be a warning regarding oxidized fats and oils. The
      contribution of diepoxy linoleic acid from ESBO might be similar to the exposure
      from oxidized fats and oils of our diet, whereas the intake of triepoxy linolenic
      acid from ESBO exceeds that from normal food by around two orders of magnitude.
      Hence use of an epoxidized edible oil virtually free of linolenic acid would be
      inconspicuous in our diet.

PMID- 16600459
TI  - Market basket survey for some heavy metals in Egyptian fruits and vegetables.
AB  - A market basket survey was carried out with the aim to assess the levels of lead
      (Pb), cadmium (Cd), copper (Cu) and zinc (Zn) in various fruits and vegetables
      sold in Egyptian markets. Atomic absorption spectrometry was used to estimate and
      evaluate the levels of these metals. The results of this survey showed that the
      average concentrations detected were ranged from 0.01 to 0.87, 0.01 to 0.15, 0.83
      to 18.3 and 1.36 to 20.9 mg/kg for Pb, Cd, Cu and Zn, respectively. The highest
      mean levels of Pb, Cd, Cu and Zn were detected in strawberries, cucumber, date
      and spinach, respectively. The levels of the metals compare with those reported
      for similar fruits and vegetables from some other parts of the world. The daily
      intakes of Pb, Cd, Cu and Zn through fruits and vegetables have also been
      estimated. They are found to be below the recommended tolerable levels proposed
      by [Joint FAO/WHO Expert Committee on Food Additives 1999. Summary and
      conclusions. In: 53rd Meeting, Rome, June 1-10, 1999] and may not constitute a
      health hazards for consumers.

PMID- 16600460
TI  - Apoptotic effects of Antrodia cinnamomea fruiting bodies extract are mediated
      through calcium and calpain-dependent pathways in Hep 3B cells.
AB  - Antrodia cinnamomea is well known in Taiwan as a traditional medicine for
      treating cancer and inflammation. The purpose of this study was to evaluate the
      apoptotic effects of ethylacetate extract from A. cinnamomea (EAC) fruiting
      bodies in Hep 3B, a liver cancer cell line. EAC decreased cell proliferation of
      Hep 3B cells by inducing apoptotic cell death. EAC treatment increased the level
      of calcium (Ca2+) in the cytoplasm and triggered the subsequent activation of
      calpain and caspase-12. EAC also initiated the mitochondrial apoptotic pathway
      through regulation of Bcl-2 family proteins expression, release of cytochrome c,
      and activation of caspase-9 in Hep 3B cells. Furthermore, the mitochondrial
      apoptotic pathway amplified the calpain pathway by Bid and Bax interaction and
      Ca2+ translocation. We have therefore concluded that the molecular mechanisms
      during EAC-mediated proliferation inhibition in Hep 3B cells were due to: (1)
      apoptosis induction, (2) triggering of Ca2+/calpain pathway, (3) disruption of
      mitochondrial function, and (4) apoptotic signaling being amplified by cross-talk
      between the calpain/Bid/Bax and Ca2+/mitochondrial apoptotic pathways.

PMID- 16600461
TI  - [Aesthetic surgery: myths and realities].

PMID- 16600462
TI  - The effect of alveolar bone loss on the load capability of restored
      endodontically treated teeth: a comparative in vitro study.
AB  - OBJECTIVES: The aim of the present investigation was to study the influence of a
      reduced bone support on the fracture resistance of endodontically treated teeth
      restored with glass fibre-reinforced posts (FRC). METHODS: 30 caries-free
      maxillary central incisors were divided into 3 groups (n=10). Endodontic
      treatment was performed. Teeth were flattened 2 mm above the cemento-enamel
      junction. Group I (control) simulated a clinical situation without horizontal
      bone loss. In group II a horizontal bone loss of 25% and in group III of 50% was
      simulated. All specimens received FRC posts and composite core restorations. All
      ceramic crowns were adhesively cemented. Specimens were exposed to thermal
      cycling and mechanical loading (TCML) and finally statically loaded until failure
      in a universal testing machine (v=1 mm/min). Non-parametric tests were used to
      compare median fracture loads between groups. Fracture modes were compared using
      Fisher's exact test. RESULTS: The median fracture load values (min/max) in [N]
      were: group I=501 (326/561), group II=422 (323/495); group III=352 (266/406),
      p=0.004. Two specimens in each group II and III failed during TCML. Statistical
      analysis revealed statistically significant differences between all test groups
      regarding maximum fracture load and mode of fracture. CONCLUSIONS: The fracture
      resistance of endodontically treated teeth restored adhesively with a FRC post,
      composite core, and all-ceramic crown is dependent on the level of surrounding
      supporting periodontal bone. Loss of alveolar bone loss due to periodontal
      disease may lead to an increased risk of failure.

PMID- 16600463
TI  - Can general dentists produce successful implant overdentures with minimal
      training?
AB  - OBJECTIVES: This study was carried out to determine whether inexperienced
      dentists can provide two-implant overdentures that are as satisfactory and of the
      same cost as those provided by experienced prosthodontists. METHODS: Edentulous
      elders were enrolled in a randomized controlled clinical trial to compare the
      effects of mandibular conventional and two-implant overdentures on nutrition.
      They were randomly assigned to groups that were treated by either an experienced
      prosthodontist or by a newly-graduated dentist with minimal training in implant
      treatment. Data for this study were obtained during the treatment of the first
      140 subjects enrolled. The change in patient ratings of satisfaction after
      treatment, laboratory costs and the number of unscheduled visits up to 6 months
      following prosthesis delivery were compared. RESULTS: Satisfaction was
      significantly higher with implant overdentures than with conventional dentures,
      but there were no differences in scores for either prosthesis between the groups
      treated by experienced specialists or new dentists. Furthermore, six of the seven
      inexperienced dentists reported that they found the mandibular two-implant
      overdenture easier to provide than the conventional denture. CONCLUSIONS: The
      results of this study suggest that general dentists can provide successful
      mandibular two-implant overdentures with minimal training.

PMID- 16600464
TI  - The physical characterization of a thermoplastic polymer for endodontic
      obturation.
AB  - OBJECTIVE: To analyze a new endodontic sealer material commercially known as
      Resilon and to describe in detail the experimental techniques employed that lead
      to the identification of the composite material. METHODS: An extensive
      structural, thermal, and physical characterization was used to identify a new
      endodontic sealer material using the following techniques: Fourier transform
      infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) analysis, X-ray
      fluorescence spectrometry (XRF) technique, X-ray diffraction (XRD) measurement,
      thermo-gravimetric analysis (TGA) and a differential scanning calorimeter (DSC).
      The surface morphology was analyzed using a scanning electron microscope (SEM).
      RESULTS: The material was identified as a composite of polycaprolactone, which is
      a polymer of the polyester family and bioactive glass, which is radiopaque
      filler. CONCLUSIONS: The Resilon sealer material is a thermoplastic synthetic
      degradable polymer (polycaprolactone), it contains bioactive glass. Its
      properties, such as strength, modulus, shape-memory effect and biodegradability
      depend on the crystalline fraction, which is affected in turn by conditions of
      crystallization. Investigation of the crystallization kinetics of PCL is of
      practical significance. It is especially necessary to study its the dynamic and
      non-isothermal crystallization process.

PMID- 16600466
TI  - Tannic acid inhibits in vitro iron-dependent free radical formation.
AB  - The antioxidant activity of tannic acid (TA), a plant polyphenol claimed to
      possess antimutagenic and anticarcinogenic activities, was studied by monitoring
      (i) 2-deoxyribose degradation (a technique for OH detection), (ii) ascorbate
      oxidation, (iii) ascorbate radical formation (determined by EPR analysis) and
      (iv) oxygen uptake induced by the system, which comprised Fe(III) complexes
      (EDTA, nitrilotriacetic acid (NTA) or citrate as co-chelators), ascorbate and
      oxygen. TA removes Fe(III) from the co-chelators (in the case of EDTA, this
      removal is slower than with NTA or citrate), forming an iron-TA complex less
      capable of oxidizing ascorbate into ascorbate radical or mediating 2-deoxyribose
      degradation. The effectiveness of TA against 2-deoxyribose degradation, ascorbate
      oxidation and ascorbate radical formation was substantially higher in the
      presence of iron-NTA (or iron-citrate) than with iron-EDTA, which is consistent
      with the known formation constants of the iron complexes with the co-chelators.
      Oxygen uptake and 2-deoxyribose degradation induced by Fe(II) autoxidation were
      also inhibited by TA. These results indicate that TA inhibits OH formation
      induced by Fe(III)/ascorbate/O(2) mainly by arresting Fe(III)-induced ascorbate
      oxidation and Fe(II) autoxidation (which generates Fe(II) and H(2)O(2),
      respectively), thus limiting the production of Fenton reagents and OH formation.
      We also hypothesize that the Fe(II) complex with TA exhibits an OH trapping
      activity, which explains the effect of TA on the Fenton reaction.

PMID- 16600465
TI  - Copper(II) and manganese(III) complexes of N'-[(2-hydroxy phenyl) carbonothioyl]
      pyridine-2-carbohydrazide: novel therapeutic agents for cancer.
AB  - c-Src is a non-receptor tyrosine kinase which plays a significant role in the
      growth mediated signaling pathway impacting cellular proliferation,
      differentiation, mobility, survival and transformation. Myristoylation of pp60(c
      src) leads to its membrane association and activation, a process catalyzed by N
      myristoyltransferase (NMT). We have shown earlier increased NMT activity in the
      early stages of colon cancer. A novel sulfur nitrogen donor ligand and its Cu(II)
      and Mn(III) complexes have been prepared and characterized using various
      physicochemical analyses. These Cu(II) and Mn(III) complexes showed cytotoxicity
      against the colon cancer cell line HT29. The IC(50) for Cu(II) and Mn(III)
      complexes were 12.2 and 16.1 microM, respectively. HT29 cells treated with Cu(II)
      and Mn(III) complexes induced apoptosis and inhibited endogenous NMT activity.
      Furthermore, they induced higher levels of hsc70 and inhibited the expression of
      c-Src. Inhibition of endogenous NMT activity by metal complexes was demonstrated
      for the first time. This study also suggested that NMT activity is crucial for
      cell survival and demonstrated that cessation in activity results in apoptosis.
      These metal complexes may prove to be novel therapeutic agents for cancer
      targeting NMT.

PMID- 16600467
TI  - Esterase EstA6 from Pseudomonas sp. CR-611 is a novel member in the utmost
      conserved cluster of family VI bacterial lipolytic enzymes.
AB  - Strain Pseudomonas sp. CR-611, previously isolated from a subtropical forest soil
      on tributyrine-supplemented plates, displays phenotypic and physiological
      properties consistent with those described for Pseudomonas fluorescens. However,
      no complete match to this species could be found after 16S rDNA comparison.
      Zymographic analysis of the strain revealed a complex lipolytic system, showing
      the presence of at least two enzymes with activity on MUF-butyrate. Alignment of
      Pseudomonas fluorescens lipase/esterase-coding sequences allowed the design of
      specific primers for family VI lipases, and the isolation and cloning of the
      resulting gene estA6. The recombinant clone obtained displayed high activity on
      fatty acid-derivative substrates, indicating that one of the lipolytic enzymes of
      the strain had been cloned. The enzyme, named EstA6, was then purified and
      characterized, showing maximum activity on short chain-length substrates under
      conditions of high temperature and neutral pH. Amino acid sequence alignment of
      EstA6 with other family VI esterases allowed identification of a highly conserved
      beta-/gamma-protobacterial cluster in family VI lipases, to which EstA6 belongs.

PMID- 16600468
TI  - Novel purification strategy for human PON1 and inhibition of the activity by
      cephalosporin and aminoglikozide derived antibiotics.
AB  - Human serum paraoxonase (PON1, EC 3.1.8.1.) is a high-density lipid (HDL)
      associated, calcium-dependent enzyme; its physiological substrates are not known.
      In this study, a new purification strategy for human PON1 enzyme was developed
      using two-step procedures, namely ammonium sulfate precipitation and sepharose-4B
      l-tyrosine-1-napthylamine hydrophobic interaction chromatography. SDS
      polyacrylamide gel electrophoresis of the enzyme indicates a single band with an
      apparent MW of 43 kDa. Overall purification rate of our method was found 227
      fold. The V(max) and K(m) of the purified enzyme were determined 227.27 EU and
      4.16 mM, respectively. The in vitro effects of commonly used antibiotics, namely
      gentamycin sulfate and cefazolin sodium was also investigated on the purified
      human serum PON1 enzyme and human liver PON1 enzyme from human hepatoma cell
      (HepG2). Gentamycin sulfate and cefazolin sodium caused a dose- and time
      dependent decrease on PON1 activity in HepG2 cells. Moreover, gentamycin sulfate
      and cefazolin sodium were effective inhibitors on purified human serum PON1
      activity with IC(50) of 0.887 and 0.0084 values, respectively. The kinetics of
      interaction of gentamycin sulfate and cefazolin sodium with the purified human
      serum PON1 indicated a different inhibition pattern. Cefazolin sodium showed a
      competitive inhibition with K(i) of 0.012+/-0.00065 mM. However, Gentamycin
      sulfate was inhibited in non-competitive manner with K(i) of 0.026+/-0.015. In
      order to determine the inhibition statue of these drugs on a living system, the
      effects of same antibiotics on PON1 enzyme activity of mouse serum PON1 and liver
      PON1 were investigated in vivo. Gentamycin sulfate (3.2 mg/kg) and cefazolin
      sodium (106.25 mg/kg) leads to the significant decrease in mouse serum PON1 after
      2, 4, 6 h and 2, 4 h drug administration, respectively. Cefazolin sodium did not
      exhibit any inhibition effect for the liver PON1, in vivo.

PMID- 16600469
TI  - Potassium disorders--clinical spectrum and emergency management.
AB  - Potassium disorders are common and may precipitate cardiac arrhythmias or
      cardiopulmonary arrest. They are an anticipated complication in patients with
      renal failure, but may also occur in patients with no previous history of renal
      disease. They have a broad clinical spectrum of presentation and this paper will
      highlight the life-threatening arrhythmias associated with both hyperkalaemia and
      hypokalaemia. Although the medical literature to date has provided a foundation
      for the therapeutic options available, this has not translated into consistent
      medical practice. Treatment algorithms have undoubtedly been useful in the
      management of other medical emergencies such as cardiac arrest and acute asthma.
      Hence, we have applied this strategy to the treatment of hyperkalaemia and
      hypokalaemia which may prove valuable in clinical practice.

PMID- 16600470
TI  - Ventricular fibrillation waveform characteristics are different in ischemic heart
      failure compared with structurally normal hearts.
AB  - BACKGROUND: For prolonged VF, perfusion of the myocardium by pre-shock chest
      compressions can improve myocardial readiness for successful defibrillation.
      Characteristics of the VF waveform correlate with the duration of VF when there
      is no structural heart disease. A "smart" automated external defibrillator (AED)
      could therefore analyze the VF waveform, determine if VF has been prolonged, and
      then direct rescuers to either deliver a shock first or chest compressions first.
      We hypothesized that ischemic heart failure might alter the waveform content of
      ventricular fibrillation compared with normal hearts, complicating the
      determination of VF duration. METHODS: Myocardial infarction was induced by
      ligating the proximal left coronary artery. Six weeks later, VF was then induced
      in 10 rats with myocardial infarction and heart failure (MI-CHF) and 9 control
      rats. Waveforms were analyzed for total signal amplitude, median frequency,
      dominant frequency and bandwidth (the frequency interval containing 50% of the
      total amplitude about the median frequency). RESULTS: All of these VF waveform
      characteristics were altered substantially in MI-CHF rats compared to normal
      controls. In particular, MI-CHF rats had decreased signal amplitude early in VF
      (p=0.02), a broader bandwidth (p=0.001) and different frequency characteristics
      over time (p<0.001). CONCLUSIONS: VF waveforms vary over time in a typical manner
      among rats with and without ischemic heart failure. However, the time-course and
      waveform characteristics of ventricular fibrillation are altered in rats with
      myocardial infarctions and ischemic heart failure compared to normal controls.
      These findings have important implications regarding the use of waveform analyses
      to determine the duration of VF.

PMID- 16600471
TI  - UV-induced generation of rare tautomers of allopurinol and 9-methylhypoxanthine -
      a matrix isolation FTIR study.
AB  - Monomers of allopurinol and 9-methylhypoxanthine were studied using the matrix
      isolation technique combined with Fourier transform infrared spectroscopy. The
      oxo tautomeric forms of both compounds were found to dominate in freshly
      deposited low-temperature argon matrices. For 9-methylhypoxanthine, a small
      amount of the hydroxy tautomer was also detected in an Ar matrix before any
      irradiation. Upon exposure of the matrices to the UV (lambda>230 nm or lambda>270
      nm) light, a proton transfer photoreaction converting the oxo forms of both
      compounds into the corresponding hydroxy tautomers occurred. Generation of
      conjugated ketenes as minor photoproducts was also observed. For 4(3H)
      pyrimidinone (a model compound for both allopurinol and 9-methylhypoxanthine),
      photoreversibility of the UV-induced oxo --> hydroxy transformation was
      experimentally proven by direct observation of the back hydroxy --> oxo
      photoreaction. The substrates (oxo tautomers) and products (hydroxy tautomers) of
      the observed phototransformations were identified by comparison of their IR
      spectra with the spectra theoretically predicted at the DFT(B3LYP)/6-31++G(d,p)
      level. The IR bands in the experimental spectra were assigned to the calculated
      normal modes.

PMID- 16600472
TI  - Sustainability of ground water quality considering land use changes and public
      health risks.
AB  - One of the major environmental issues of concern to policy-makers is the
      increased vulnerability of ground water quality (GWQ). Another issue of equal
      interest is the sustainability of natural resources for future generations. To
      understand the sustainability of the natural resources such as water in general,
      one needs to understand the impact of future land use changes on the natural
      resources. This work proposes a methodology to address sustainability of GWQ
      considering land use changes, aquifer vulnerability to multiple contaminants, and
      public health risks. The methodology was demonstrated for the Sumas-Blaine
      aquifer in Washington State. The land transformation model predicted that nearly
      60 percent of the land use practices would change in the Sumas-Blaine Aquifer by
      the year 2015. The accuracy of the LTM model predictions increased to greater
      levels as the spatial resolution was decreased. Aquifer vulnerability analysis
      was performed for major contaminants using the binary logistic regression (LR)
      method. The LR model, along with the predicted future land use, was used to
      estimate the future GWQ using two indices-carcinogenic and non-carcinogenic
      ground water qualities. Sustainability of GWQ was then analyzed using the concept
      of 'strong' sustainability. The sustainability map of GWQ showed improvements in
      many areas where urbanization is expected to occur. The positive impact of
      urbanization on GWQ is an indication of the extensive damage caused by existing
      agricultural activities in the study area.

PMID- 16600473
TI  - Choosing policy instruments for controlling ozone depleting substances in a
      developing context: the case of Chile.
AB  - Chile ratified the Montreal Protocol in 1990 which sets out an agenda for the
      reduction and then elimination of ozone depleting substances (ODS); however, by
      1998 the country had not yet defined a strategy to encourage greater compliance,
      so that in the same year the National Environmental Commission decided to examine
      the policy options available. This paper examines the process followed to develop
      this strategy. As a first step it was necessary to look at how far the implicit
      policy of "business as usual" could be stretched without jeopardizing Chile's
      compliance obligations. A second step included quantifying compliance costs and
      their impact on different policy instruments and so policy choice. Finally, the
      attitudes of decision-makers or participants were identified, by interviews with
      officials of the different public agents involved, in order to weigh their views
      about policy. A strategy was proposed, based on this information, which the
      Chilean regulator has used, although not in its entirety. The methodology
      developed could well be useful for developing-country Protocol signatories
      building their own appropriate compliance strategy.

PMID- 16600474
TI  - The Paton individual-based model legacy.
AB  - Ray Paton oversaw the creation of a long lineage of Individual-based Models
      (IbMs) and this paper discusses the five most successful. All of these concern
      the development of adaptation, covering both evolutionary time and organism
      lifetime (somatic time). Of the five models discussed here, the first is based on
      a plant-herbivore model, the other four are based on a substrate-bacteria model,
      with the option of antibiotics.

PMID- 16600475
TI  - Jasmonates in cancer therapy.
AB  - Several groups have reported in recent years that members of the plant stress
      hormones family of jasmonates, and some of their synthetic derivatives, exhibit
      anti-cancer activity in vitro and in vivo. Jasmonates increased the life span of
      EL-4 lymphoma-bearing mice, and exhibited selective cytotoxicity towards cancer
      cells while sparing normal blood lymphocytes, even when the latter were part of a
      mixed population of leukemic and normal cells drawn from the blood of chronic
      lymphocytic leukemia (CLL) patients. Jasmonates join a growing number of old and
      new cancer chemotherapeutic compounds of plant origin. Three mechanisms of action
      have been proposed to explain the anti-cancer activity of jasmonates. These
      include: (1) The bio-energetic mechanism-jasmonates induce severe ATP depletion
      in cancer cells via mitochondrial perturbation; (2) The re-differentiation
      mechanism-jasmonates induce re-differentiation in human myeloid leukemia cells
      via mitogen-activated protein kinase (MAPK) activity; (3) The reactive oxygen
      species (ROS)-mediated mechanism-jasmonates induce apoptosis in lung carcinoma
      cells via the generation of hydrogen peroxide, and pro-apoptotic proteins of the
      Bcl-2 family. Several similarities between the effects of jasmonates on plant and
      cancer cells have been recorded, suggesting that additional analysis of jasmonate
      effects in plant cells may contribute to a deeper understanding of the anti
      cancer actions of these compounds. Those similarities include: induction of cell
      death, suppression of proliferation and cell cycle arrest, MAPK induction, ROS
      generation, and enhancement of heat-shock proteins (HSP) expression. Finally,
      jasmonates can induce death in drug-resistant cells. The drug resistance was
      conferred by either p53 mutation or P-glycoprotein (P-gp) over-expression. In
      summary, the jasmonate family of novel anti-cancer agents presents new hope for
      the development of cancer therapeutics, which should attract further scientific
      and pharmaceutical interest.

PMID- 16600476
TI  - Multivariate analysis of trace metals in textile effluents in relation to soil
      and groundwater.
AB  - This paper deals with the multivariate analysis of metal data in effluents, soil
      and groundwater to find the distribution and source identification of the
      selected metals in the three media. Samples were collected from three textile
      industries located in Hattar Industrial Estate, Pakistan. Metals were estimated
      by flame atomic absorption spectrophotometry. The results showed elevated levels
      of Cr, Pb, Ni, Co, Fe, Ca, Na, K and Zn in these media, following the order:
      soil>effluent>water. Principle component analysis (PCA) of the data showed that
      the textile effluents are contaminating the soil wherein Cr and Pb were dominant
      toxic metals having concentrations of 5.96 mg/kg and 4.46 mg/kg, respectively.
      Other toxic metals such as Co, Cd, Zn, Ni, Mn and Fe, were found to have common
      origin in the textile effluents. The correlation study along with linear
      regression and PCA, supported the fact that various elevated metal concentrations
      emerged from the textile industrial effluents ultimately leading to contamination
      of the soil and groundwater in their proximity. The estimated metal levels in the
      water/soil system are compared with the safe limits laid down by WHO.

PMID- 16600477
TI  - Degradation of 2,4-dichlorophenol by using glow discharge electrolysis.
AB  - Degradation of 2,4-dichlorophenol (2,4-DCP) in aqueous by glow discharge
      electrolysis (GDE) has been investigated. Ultraviolet (UV) absorption spectra,
      atomic force microscopy (AFM), high performance liquid chromatography (HPLC) and
      gas chromatogram-mass spectrum (GC/MS) are used to monitor the degradation
      process and to identify the major oxidation intermediate products. It has been
      found that 2,4-DCP undergoes a series of intermediate step, which leads to form a
      number of intermediate products, mainly isomeric chlorophenols and aliphatic
      acids. These products are further oxidized, eventually, mineralized into CO(2)
      and Cl(-). A degradation pathway for 2,4-DCP is proposed on the basis of
      detection of intermediate compounds.

PMID- 16600478
TI  - Degradation of recalcitrant compounds from stabilized landfill leachate using a
      combination of ozone-GAC adsorption treatment.
AB  - Laboratory experiments were undertaken to investigate the treatment performances
      of ozonation alone and/or its combination with granular activated carbon (GAC)
      adsorption for raw leachate from the NENT landfill (in Hong Kong). To improve its
      removal of recalcitrant contaminants from the leachate, the surface of GAC was
      oxidized with ozone prior to treatment. With respect to ozone dose and pH, the
      removal of COD and/or NH(3)-N from ozonation alone and combined ozone-GAC
      adsorption were evaluated and compared to those of other physico-chemical
      treatments in some reported studies. The removal mechanism of recalcitrant
      compounds by ozone-GAC adsorption treatment was presented. Among the various
      treatments studied, the combination of ozone-GAC adsorption using ozone-modified
      GAC had the highest removal for COD (86%) and/or NH(3)-N (92%) compared to
      ozonation alone (COD: 35%; NH(3)-N: 50%) at the same initial COD and/or NH(3)-N
      concentrations of 8000 and 2620 mg/L, respectively. Although the integrated
      treatment was more effective than ozonation alone for treating stabilized
      leachate, the results suggested that it could not generate treated effluent that
      complied with the COD limit of lower than 200 mg/L and the NH(3)-N discharge
      standard of less than 5 mg/L. Therefore, further biological treatments to
      complement the degradation of the leachate are still required to meet the
      environmental legislation.

PMID- 16600479
TI  - Fluoride in drinking water and its removal.
AB  - Excessive fluoride concentrations have been reported in groundwaters of more than
      20 developed and developing countries including India where 19 states are facing
      acute fluorosis problems. Various technologies are being used to remove fluoride
      from water but still the problem has not been rooted out. In this paper, a broad
      overview of the available technologies for fluoride removal and advantages and
      limitations of each one have been presented based on literature survey and the
      experiments conducted in the laboratory with several processes. It has been
      concluded that the selection of treatment process should be site specific as per
      local needs and prevailing conditions as each technology has some limitations and
      no one process can serve the purpose in diverse conditions.

PMID- 16600480
TI  - Recovery of gallium and vanadium from gasification fly ash.
AB  - The Puertollano Integrated Coal Gasification Combined Cycle (IGCC) Power Plant
      (Spain) fly ash is characterized by a relatively high content of Ga and V, which
      occurs mainly as Ga2O3 and as Ga3+ and V3+ substituting for Al3+ in the Al-Si fly
      ash glass matrix. Investigations focused on evaluating the potential recovery of
      Ga and V from these fly ashes. Several NaOH based extraction tests were performed
      on the IGCC fly ash, at different temperatures, NaOH/fly ash (NaOH/FA) ratios,
      NaOH concentrations and extraction times. The optimal Ga extraction conditions
      was determined as 25 degrees C, NaOH 0.7-1 M, NaOH/FA ratio of 5 L/kg and 6 h,
      attaining Ga extraction yields of 60-86%, equivalent to 197-275 mg of Ga/kg of
      fly ash. Re-circulation of leachates increased initial Ga concentrations (25-38
      mg/L) to 188-215 mg/L, while reducing both content of impurities and NaOH
      consumption. Carbonation of concentrated Ga leachate demonstrated that 99% of the
      bulk Ga content in the leachate precipitates at pH 7.4. At pH 10.5 significant
      proportions of impurities, mainly Al (91%), co-precipitate while >98% of the bulk
      Ga remains in solution. A second carbonation of the remaining solution (at pH
      7.5) recovers the 98.8% of the bulk Ga. Re-dissolution (at pH 0) of the
      precipitate increases Ga purity from 7 to 30%, this being a suitable Ga end
      product for further purification by electrolysis. This method produces higher
      recovery efficiency than currently applied for Ga on an industrial scale. In
      contrast, low V extraction yields (<64%) were obtained even when using extreme
      alkaline extraction conditions, which given the current marked price of this
      element, limits considerably the feasibility of V recovery from IGCC fly ash.

PMID- 16600481
TI  - Potential of Sargassum wightii biomass for copper(II) removal from aqueous
      solutions: application of different mathematical models to batch and continuous
      biosorption data.
AB  - This paper reports biosorption of copper(II) ions onto Sargassum wightii biomass
      in batch and continuous mode of operation. Batch experiments were fundamentally
      aimed to determine the favorable pH for copper(II) biosorption. Langmuir model
      was used to describe the copper(II) biosorption isotherm and maximum uptake of
      115 mg/g was obtained at pH 4.5. Continuous experiments in a packed column (2 cm
      i.d. and 35 cm height) were performed to study the influence of bed height, flow
      rate and inlet solute concentration on copper(II) biosorption. The highest bed
      height (25 cm), lowest flow rate (5 ml/min) and highest inlet Cu(II)
      concentration (100 mg/l) resulted in highest copper(II) uptake of 52.6 mg/g,
      compared to other conditions examined. Column data obtained at different
      conditions were described using the Thomas, Yoon-Nelson and modified dose
      response models. All three models were able to predict breakthrough curves; in
      particular, the breakthrough curve prediction by the Thomas and Yoon-Nelson
      models were found to be very satisfactory. Also, the well-established design
      model, the Bed depth-service time (BDST) model was used to analyze the
      experimental data. The BDST model plot at 5 ml/min (flow rate) and 100 mg/l
      (inlet solute concentration) was used to predict bed depth-service time data at
      different conditions. The BDST model predicted values always coincide with
      experimental values with high correlation coefficients.

PMID- 16600482
TI  - Removal of methylene blue from aqueous solution by chaff in batch mode.
AB  - A new adsorbent system for removing methylene blue (MB) from aqueous solutions
      has been investigated. This new adsorbent is cereal chaff, an agriculture product
      in middle-west region in China. Variables of the system, including biosorption
      time, chaff dose, pH, salt concentration and initial MB concentration, were
      adopted to study their effects on MB removal. The results showed that as the dose
      of chaff increased, the percentage of MB sorption increased accordingly. There
      was no significant difference in the dye concentration remaining when the pH was
      increased from 4.0 to 11.0. The salt concentration has negative effect on MB
      removal. At the experimental range of MB concentration, the amount of MB adsorbed
      onto per unit mass of chaff (q(e)) is direct ratio to MB initial concentration
      (c(0)). The equilibrium data were analyzed using five equilibrium models, the
      Langmuir, the Freundlich, the Redlich-Peterson, the Koble-Corrigan and the Temkin
      isotherms. The results of non-linear regressive analysis are that the isotherms
      of Langmuir, Redlich-Peterson and Koble-Corrigan are better fit than the
      isotherms of Freundlich and Temkin at different temperatures according to the
      values of determined coefficients (R(2)) and Chi-square statistic (chi(2)). The
      maximum equilibrium capacities of chaff from Langmuir models are 20.3, 25.3 and
      26.3 mg g(-1) at 298, 318 and 333K, respectively. Using the equilibrium
      concentration constants obtained at different temperatures, various thermodynamic
      parameters, such as DeltaG(0), DeltaH(0) and DeltaS(0), have been calculated. The
      thermodynamics parameters of MB/chaff system indicate spontaneous and endothermic
      process. It was concluded that an increase in temperature results in a bigger MB
      loading per unit weight of the chaff.

PMID- 16600483
TI  - Reaction mechanisms in the geopolymeric conversion of inorganic waste to useful
      products.
AB  - High-performance materials for construction, waste immobilisation and an ever
      growing range of niche applications are produced by the reaction sequence known
      as 'geopolymerisation'. In this process, an alkaline activating solution reacts
      with a solid aluminosilicate source, with solidification possible within minutes
      and very rapid early strength development. Geopolymers have been observed to
      display remarkable chemical and thermal stability, but due to their largely X-ray
      amorphous nature have only recently been accurately characterised. It has
      previously been shown that both fly ash and ground granulated blast furnace slag
      are highly effective as solid constituents of geopolymer reaction slurries,
      providing readily soluble alumina and silica that undergo a dissolution
      reorientation-solidification process to form a geopolymeric material. Here a
      conceptual model for geopolymerisation is presented, allowing elucidation of the
      individual mechanistic steps involved in this complex and rapid process. The
      model is based on the reactions known to occur in the weathering of
      aluminosilicate minerals under alkaline conditions, which occur in a highly
      accelerated manner under the conditions required for geopolymerisation.
      Transformation of the waste materials to the mixture of gel and
      nanocrystalline/semicrystalline phases comprising the geopolymeric product is
      described. Presence of calcium in the solid waste materials affects the process
      of geopolymerisation by providing extra nucleation sites for precipitation of
      dissolved species, which may be used to tailor setting times and material
      properties if desired. Application of geopolymer technology in remediation of
      toxic or radioactive contaminants will depend on the ability to analyse and
      predict long-term durability and stability based on initial mix formulation. The
      model presented here provides a framework by which this will be made possible.

PMID- 16600484
TI  - Cosorption of zinc and glyphosate on two soils with different characteristics.
AB  - Agricultural application of large amounts of glyphosate [N-(phosphonomethyl)
      glycine] may affect soil metal behaviors to some extend, because glyphosate can
      react with many kinds of metals to form metal complexes. Cosorption of Zn and
      glyphosate on a Red soil (RS, Udic Ferrosols) and a Wushan soil (WS, Anthrosol)
      was studied. In comparison with the WS, the RS has less adsorption capacity for
      Zn and higher for glyphosate. The presence of glyphosate decreased Zn adsorption
      on the two soils, which are resulted from the decreased equilibrium solution pH
      caused by the added glyphosate, and also the formation of water-soluble complexes
      of glyphosate with solution Zn(2+) that had lower affinity to soil surface in
      comparison with Zn(2+) itself. Such effect is more significant on the RS than on
      the WS, mainly because of the less adsorption quantity of Zn on the former one.
      On the contrary, the presence of Zn increased the adsorption quantities of
      glyphosate on the RS and WS, which is resulted from the decreasing pH value of
      the equilibrium solution caused by Zn(2+) exchange with H(+) ions of soil
      surface. Such results suggest that glyphosate in field may increase the mobility
      and bioavailability of Zn and correspondingly increase its environmental risk.

PMID- 16600485
TI  - Environmental acceptability of beneficial use of waste as construction material-
      state of knowledge, current practices and future developments in Europe and in
      France.
AB  - Since a decade, numerous industrial and public initiatives have been launched in
      order to make knowledge, practices and mentalities evolve in relation to the
      acceptability of using waste instead of raw material as construction product. The
      objectives of these initiatives have been to evaluate current practices and to
      make new solutions and beneficial use channels emerge. At the same time
      scientific and standardisation communities have developed methodologies and tools
      to fit with the assessment needs expressed by industrialists and public decision
      makers. In spite of that, some factors, some of them being cross-linked, make the
      perpetuation of beneficial use channels or even the concretisation of research
      projects difficult. To cope with this situation, in the framework of sustainable
      development applied to natural and alternative material, the French Directorate
      of Road has launched a project aiming at providing public contracting authorities
      with a document gathering both technical and environmental requirements that they
      can prescribe in public market tender calls to promote the use of waste and out
      of-technical-specifications-material. This paper deals with the presentation of
      this project focusing more specifically on the approach to assess both technical
      and environmental acceptability of waste and out-of-technical-specifications
      material to be used as alternative material in road construction in France. The
      current European situation is first described and this paper finally discusses
      briefly the other key aspects--than environmental acceptability--that have to be
      taken into account to succeed waste beneficial use.

PMID- 16600486
TI  - Dynamic determination of the concentration of volatile alcohols in a fixed bed of
      zeolite 13X by FT-IR.
AB  - A series of dynamic adsorptions of volatile methanol, ethanol, and iso-propanol
      (IPA) onto zeolite 13X were studied. Instead of traditional gas chromatography
      (GC), a gas-phase Fourier Transformation-IR (FT-IR) spectrometer was used to
      measure the evolution of concentrations of these volatile alcohols due to its
      quick response to the instantaneous changes of the gas concentration. Even though
      it has rarely been used in dynamic adsorption experiments in the literature, an
      FT-IR equipped with a constant-temperature gas cell was shown to be adequate to
      obtain breakthrough curves. In this study, the experiments were carried out at
      different gas flow rates and feed concentrations for each type of alcohol.
      Significant influences of the operating conditions on the breakthrough time, the
      shape of the breakthrough curve, and the uptake of each alcohol were found. A
      simple mathematical model proposed by Yoon and Nelson was applied to fit the
      experimental data. Good consistency between the experimental data and the
      regressed breakthrough curves was observed.

PMID- 16600487
TI  - Comparison between electrocoagulation and chemical precipitation for metals
      removal from acidic soil leachate.
AB  - This paper provides a quantitative comparison between electrocoagulation and
      chemical precipitation based on heavy metals (Cd, Cr, Cu, Ni, Pb and Zn) removal
      from acidic soil leachate (ASL) at the laboratory pilot scale. Chemical
      precipitation was evaluated using either calcium hydroxide or sodium hydroxide,
      whereas electrocoagulation was evaluated via an electrolytic cell using mild
      steel electrodes. Chemical precipitation was as effective as electrocoagulation
      in removing metals from ASL having low contamination levels (30 mg Pbl(-1) and 18
      mg Znl(-1)). For ASL enriched with different metals (each concentration of metals
      was initially adjusted to 100 mg l(-1)), the residual Cr, Cu, Pb and Zn
      concentrations at the end of the experiments were below the acceptable level
      recommended for discharge in sewage urban works (more than 99.8% of metal was
      removed) using either electrocoagulation or chemical precipitation. Cd was more
      effectively removed by electrochemical treatment, whereas Ni was easily removed
      by chemical treatment. The cost for energy, chemicals and disposal of metallic
      residue of electrocoagulation process ranged from USD 8.83 to 13.95 tds(-1),
      which was up to five times lower than that recorded using chemical precipitation.
      Highly effective electrocoagulation was observed as the ASL was specifically
      enriched with high concentration of Pb (250-2000 mg Pbl(-1)). More than 99.5% of
      Pb was removed regardless of the initial Pb concentration imposed in ASL and, in
      all cases, the residual Pb concentrations (0.0-1.44 mg l(-1)) were below the
      limiting value (2.0 mg l(-1)) for effluent discharge in sewage works.

PMID- 16600488
TI  - Performance of TX-100 and TX-114 for the separation of chrysoidine dye using
      cloud point extraction.
AB  - Cloud point extraction (CPE) is carried out to extract chrysoidine dye from
      aqueous solution using two different non-ionic surfactants, TX-100 and TX-114.
      The effects of different operating parameters, e.g., concentrations of
      surfactant, dye and salt, temperature, pH on extraction of both dye and
      surfactant have been studied in detail. The extraction of dye increases with
      temperature, surfactant concentration and salt concentration. Various design
      parameters of a CPE process have been estimated by developing correlations for
      dye solubilization and fractional coacervate phase volume with the operating
      conditions. The equilibrium solubilization data at four different temperatures
      follow Langmuir type isotherm. A method is presented to calculate the feed
      surfactant concentration required for the removal of dyes up to a level of
      3.82x10(-6) M. The developed correlations may be useful to design a cloud point
      extractor of a desired efficiency.

PMID- 16600489
TI  - Cadmium fixation by synthetic hydroxyapatite in aqueous solution--thermal
      behaviour.
AB  - This study deals with the mechanism of the cadmium uptake by synthetic
      hydroxyapatite (HA: Ca10(PO4)6(OH)2) in aqueous solution. The rate of cadmium
      fixation by hydroxyapatite was investigated at 10 and 50 degrees C using batch
      experiments. Inductively coupled plasma atomic emission spectrometry, X-ray
      diffraction, FT-IR spectroscopy and electron microscopy were used to characterize
      the starting HA and the samples. The thermal behaviour of the powders was
      determined with the help of three thermoanalytical techniques (TGA, DTA, and MS)
      and temperature programmed X-ray diffraction. Cadmium immobilization kinetics can
      be divided into two steps: substitution of Ca2+ ions by Cd2+ in the HA lattice at
      the particle's surface, followed by their incorporation into the hydroxyapatite
      bulk. This results in the formation of an apatite solid solution, which is very
      important because in this way decontamination and storage can be performed with
      the same material.

PMID- 16600490
TI  - Microwave assisted catalytic wet air oxidation of H-acid in aqueous solution
      under the atmospheric pressure using activated carbon as catalyst.
AB  - Catalytic wet air oxidation (CWAO) is a promising method for the treatment of
      heavily contaminated wastewater. However, its application is restricted due to
      severe operation conditions (high pressure and high temperature). A microwave
      (MW) assisted oxidation method was investigated aiming to treat heavily
      contaminated wastewater under milder conditions. H-acid (1-amino-8-naphthol-3, 6
      disulfonic acid) was selected as target compound to evaluate the performance of
      this novel process. The removal of H-acid and TOC (total organic carbon) for H
      acid solution of 3000 mg/L reached as high as 92.6% in 20 min and 84.2% in 60
      min, respectively under optimal conditions. The existence of activated carbon and
      oxygen proved to be critical for effective treatment. The activated carbon acted
      not only as a catalyst for H-acid decomposition, but also as a special material
      for the absorption of MW energy. Air was supplied to the reactor as an oxygen
      source at constant flows. The amino group in H-acid was converted ultimately into
      nitrate, and sulfonic group into sulfate. This observation gave an evidence of H
      acid mineralization although other organic intermediates were unable to be
      determined. The value of BOD(5)/COD (ratio of 5d biochemical oxygen demand to
      chemical oxygen demand) increased from 0.008 to 0.467 indicating a significant
      improvement of biodegradability for the solution, which is beneficial for the
      further biological treatment of the wastewater.

PMID- 16600491
TI  - Deportment and management of metals produced during combustion of CCA-treated
      timbers.
AB  - Experiments were conducted to study CCA-treated wood combustion over a range of
      temperature and oxygen concentrations with a view to understanding the factors
      affecting energy and metals recovery from waste treated timber. CCA-treated wood
      was burned in a furnace at temperatures from 400 to 940 degrees C and oxygen
      concentrations between 5 and 21%. The ash and condensed volatiles were digested
      for total concentrations of metals and subjected to leaching tests to determine
      the stabilized concentrations of metals. Arsenic volatilisation increased with
      increasing furnace temperature whereas the copper and chromium reported mainly to
      the ash product. The effect of oxygen concentration was weak although it appeared
      that more arsenic volatilises at higher oxygen concentrations. However, a larger
      proportion of the arsenic in the ash generated at lower oxygen concentrations is
      solubilised during leaching tests, with the result that the concentration of
      stabilized arsenic in the ash is relatively unaffected by oxygen concentration.

PMID- 16600492
TI  - Simulation of a spray scrubber performance with Eulerian/Lagrangian approach in
      the aerosol removing process.
AB  - In this study, a mathematical model has been developed to simulate the
      performance of a spray scrubber in an industrial ammonium nitrate plant. The
      model is based on the Lagrangian approach for the droplets movement and particle
      source in cell (PSI-CELL) model for calculating the droplet concentration
      distribution. Consequently, unlike former research, the emphasis is on the
      droplet dynamic behavior. In the current study, for approaching a realistic
      model, a droplet size distribution rather than average diameter, and also liquid
      film formation rather than uniform and constant droplet flow rate has been
      applied. Also, the Eulerian method has been used for the calculation of the
      particles removal efficiency and energy balance has been applied on the gas to
      estimate the droplet size distribution. In the experimental section, the
      concentration of particles and their size distribution in both inlet and outlet
      gas of the studied scrubber has been measured for the validation of the predicted
      particles collection efficiency. In addition, the temperature of the gas at
      inlet, outlet and in the middle of the tower has been measured for the
      confirmation of the predicted droplet size distribution in the tower. A good
      consistency between the model and data has been observed. After the model is
      validated, it is used to investigate the various variable profiles such as liquid
      film, total projected surface area of the droplets, velocity profile of the
      droplets and some of the other parameters in the spray scrubbers.

PMID- 16600493
TI  - Recycling of auto shredder residue.
AB  - Currently, about 75% of end-of-life vehicle's (ELV) total weight is recycled in
      EU countries. The remaining 25%, which is called auto shredder residues (ASR) or
      auto fluff, is disposed of as landfill because of its complexity. It is a major
      challenge to reduce this percentage of obsolete cars. The European draft
      directive states that by the year 2006, only 15% of the vehicle's weight can be
      disposed of at landfill sites and by 2015, this will be reduced to 5%. The draft
      directive states that a further 10% can be incinerated. The quantities of
      shredder fluff are likely to increase in the coming years. This is because of the
      growing number of cars being scrapped, coupled with the increase in the amount of
      plastics used in cars. In Sweden, some current projects are focusing on recycling
      of ASR material. In this paper some different alternatives for using this
      material are reported. The hypothetical injection of ASR into a blast furnace
      concentrating on ASR's effect to some blast furnace (BF) parameters has been
      completed using a blast furnace mass balance model. As a result, in principle,
      ASR can be used as reducing agent in the BF process if certain conditions are
      met. The particle size of ASR material must be controlled to ensure optimal
      gasification of the material in the raceway. Regarding the chemical composition
      of ASR, the non-ferrous content can affect the pig iron quality, which is
      difficult to rectify at a later point. The most attractive recycling alternative
      is to use the products obtained from pyrolysis of ASR in appropriate
      metallurgical processes.

PMID- 16600494
TI  - Influence of temperature on the electrical conductivity of leachate from
      municipal solid waste.
AB  - A bioreactor landfill is designed to manage municipal solid waste, through
      accelerated waste biodegradation, and stabilisation of the process by means of
      the controlled addition of liquid, i.e. leachate recirculation. The measurement
      of electrical resistivity by Electrical Resistivity Tomography (ERT) allows to
      monitor water content present in the bioreactors. Variations in electrical
      resistivity are linked to variations in moisture content and temperature. In
      order to overcome this ambiguity, two laboratory experiments were carried out to
      establish a relationship between temperature and electrical conductivity: the
      first set of measurements was made for leachate alone, whereas the second set was
      made with two different granular media saturated with leachate. Both experiments
      confirm a well known increase in conductivity of about 2% degrees C(-1). However,
      higher suspended matter concentrations lead to a lower dependence of electrical
      conductivity on temperature. Furthermore, for various porous media saturated with
      an identical leachate, the higher the specific surface of the granular matrix,
      the lower the effective bulk electrical conductivity. These observations show
      that a correct understanding of the electrical properties of liquids requires the
      nature and (in particular) the size of the electrical charge carriers to be taken
      into account.

PMID- 16600495
TI  - ERPs and deviance detection: visual mismatch negativity to repeated visual
      stimuli.
AB  - Previous studies showed a visual analogue of the mismatch negativity (MMN) event
      related potential (ERP), which is elicited by violating some sensory regularity.
      Separating physical change from violating a regularity, here we show that the
      visual MMN (vMMN) is elicited by regularity violations that do not involve
      physical stimulus change. Adult participants were presented with a series of red
      black and green-black checkerboard patterns delivered regularly in an RRGGRRGG
      ... order. Infrequently (p=0.1) this regularity was broken by repeating a
      stimulus one additional time (e.g. RRGGRRR). ERPs elicited by irregular stimulus
      repetitions were negatively displaced compared to those elicited both by regular
      repetition and regular change in two latency ranges: 100-140 ms and 220-260 ms.
      Whereas the first of these two negative ERP differences appears to be sensitive
      to stimulus repetition per se, the second difference can be identified as a vMMN
      response to violating the sequential regularity. Thus, similarly to its auditory
      counterpart, vMMN reflects deviance-(regularity-violation) rather than change
      detection processes.

PMID- 16600496
TI  - Decreased neurofilament density in large myelinated axons of metallothionein-I,
      II knockout mice.
AB  - Metallothioneins (MTs) are small proteins, two isoforms (I, II) of which bind
      metals. Their physiological role has been difficult to establish, but recent
      reports suggested that they serve an important function in nerve repair and in
      the protection against oxidative stress in the peripheral nervous system. We
      previously reported a decreased axon calibre in the large myelinated fibres of
      the phrenic nerve in the MT-I, II double knock out (MT-I, II KO) mouse model. We
      propose that this could be due to the effects of oxidative stress on
      neurofilaments (NFs). In this study, we examined the same subset of large
      myelinated axons using transmission electron microscopy (TEM). There was a
      decreased NF density in the axons of MT-I, II KO phrenic nerve (P<0.005). This
      observation may have novel therapeutic implications in the treatment of
      amyotrophic lateral sclerosis (ALS), particularly as the terminal phases of the
      disease involve respiratory insufficiency.

PMID- 16600497
TI  - Calbindin is predominantly expressed in nitrergic neurons in rat esophagus.
AB  - We used immunohistochemistry to investigate the colocalization pattern of
      calbindin D28k (Calb) with nitric oxide and acetylcholine in myenteric neurons in
      the rat esophagus and compared it to that in the ileum or distal colon. The
      proportion of Calb-immunoreactive (IR) neurons to the total neurons in the
      esophagus (8%) was lower than that in the ileum (38%) or distal colon (27%). A
      majority (84%) of the esophageal Calb-IR neurons were uniaxonal neurons. On the
      other hand, 88% and 66% of Calb-IR neurons in the ileum and distal colon,
      respectively, had Dogiel type II morphology, while most of the others were Dogiel
      type I neurons. Double immunolabeling indicated that most (87%) of the esophageal
      Calb-IR neurons were nitric oxide synthase (NOS) positive and a minority (21%)
      were choline acetyltransferase (ChAT) positive. Most (93% and 89%, respectively)
      of the Calb-IR neurons in the ileum and distal colon showed ChAT immunoreactivity
      and only a small number exhibited NOS immunoreactivity in the ileum and distal
      colon. In the esophagus, some of Calb-IR nerve endings surrounding the myenteric
      neurons were NOS positive, but no Calb immunoreactivity was found on the motor
      endplates of the striated muscles. Therefore, the present study revealed that
      most of the Calb-IR neurons in the esophagus are nitrergic, and it suggested that
      the Calb-IR neurons might be primarily involved in interneuronal roles in the
      esophageal nervous system.

PMID- 16600498
TI  - Total antioxidant capacity of cerebrospinal fluid is decreased in patients with
      motor neuron disease.
AB  - Oxidative stress has been associated with motor neuron disease (MND). The human
      body has several antioxidant defense systems to repair the damage caused by
      oxidative stress. The activity of these systems is thought to be reduced in
      neurodegenerative diseases, which may increase the level of oxidative damage and
      be a contributing factor to motor neuron death. In the present study, we compared
      the total antioxidant capacity (TAC) of human serum and cerebrospinal fluid (CSF)
      of MND patients with that of a control group including patients with migraine,
      tension headache and psychiatric disorders. Within-subject serum and CSF TAC were
      strongly correlated (r=0.639; p=0.000), and CSF TAC was significantly lower in
      MND patients as compared to controls after adjustment for known influencing
      factors (112.7 micromol Fe/L+/-11.7 versus 135.2 micromol Fe/L+/-19.7; p=0.012).
      No differences in serum or CSF TAC were observed among the clinical forms of MND
      considered in this work. In conclusion, the CSF TAC was strongly correlated with
      serum TAC, and a decrease in CSF TAC was demonstrated in MND patients compared to
      controls that was not independent from serum antioxidants, this translating in a
      systemic (but prevailing in the CNS) oxidative damage in this pathology.

PMID- 16600499
TI  - Electrical stimulation of locus coeruleus strengthens the surround inhibition in
      layer V barrel cortex in rat.
AB  - It is believed that locus coeruleus (LC) influences the sensory information
      processing. However, its role in cortical surround inhibitory mechanism is not
      well established. In this experiment, using controlled mechanical displacement of
      whiskers; we investigated the effect of electrical stimulation of LC on response
      of layer V barrel cortical neurons in anesthetized rat. LC was stimulated 0, 50,
      100, 200 and 400 ms before principal or adjacent whiskers deflection. For
      assessing the effect of LC stimulation on inhibitory receptive filed of barrel
      neurons, adjacent whisker was also deflected 20 ms before principal whisker
      deflection, and LC stimulation was applied 0-400 ms before principal whisker
      displacement. We found that LC stimulation increase the response magnitude of
      layer V neurons to principal whisker deflection (significant in 50-400 ms
      intervals). This increase was also observed in response to adjacent whisker
      deflection (significant in 100 ms interval). The response latency of neurons was
      decreased when LC was stimulated 400 ms before principal whisker deflection but
      LC stimulation did not affect the neuronal response latency to adjacent whisker
      displacement. Inhibitory effect of adjacent whisker deflection on neuronal
      response magnitude was increased by LC stimulation, tested in combined whisker
      displacement. These findings suggest that LC, by modulating the neuronal
      responses, enhances the neuronal responsiveness to sensory stimuli and increases
      their surround inhibition in cortex.

PMID- 16600500
TI  - Expression of the alpha1A-adrenergic receptor in schizophrenia.
AB  - The alpha1-adrenergic receptors may contribute to cognitive functions relevant to
      schizophrenia. Following the discovery of an association between polymorphisms in
      the regulatory region of the alpha1A-adrenergic receptor and schizophrenia we
      investigated the expression of mRNA for this receptor between schizophrenics
      (n=19) and controls (n=19) using a TaqMan approach in post-mortem brains. No
      differences were found suggesting that mRNA levels are not altered in
      schizophrenia. Genotypic data for the subjects found that possession of the
      previously associated genotypes did not convey a difference in mRNA expression
      suggesting that these polymorphisms do not affect the level of transcription.

PMID- 16600501
TI  - Bereitschaftspotentials recorded from the lateral part of the superior frontal
      gyrus in humans.
AB  - To demonstrate the Bereitschaftspotentials (BPs) over the high lateral convexity
      in the superior frontal gyrus, movement-related cortical potentials with respect
      to the middle finger extension were recorded in seven patients with refractory
      epilepsy who underwent subdural implantation of platinum electrode grids and/or
      strips covering the high lateral frontal convexity. In two out of the seven
      patients, BPs were recorded from the electrodes placed on the superior frontal
      gyrus in the vicinity of the border between the medial and lateral frontal lobes,
      which were distinct from those recorded from the primary sensorimotor cortex. The
      results suggest the possible contribution of either the lateral dorsal non
      primary motor area or the SMA to the generation of the BPs.

PMID- 16600502
TI  - Autoantibodies that recognize functional domains of hnRNPA1 implicate molecular
      mimicry in the pathogenesis of neurological disease.
AB  - As a model for molecular mimicry in neurological disease, we study people
      infected with human T-lymphotropic virus type 1 (HTLV-1) who develop HTLV-1
      associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune-mediated
      disease of the central nervous system (CNS). In HAM/TSP, data suggests molecular
      mimicry is the result of cross-reactive antibodies between HTLV-1-tax and
      heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a protein over-expressed
      in human CNS neurons. The hnRNP A1 epitope recognized by autoantibodies was
      unknown. In this study, we hypothesized that antibodies purified from HAM/TSP
      patients would react with functionally significant domains of hnRNP A1. Western
      blotting of functionally significant deletion mutants and overlapping fusion
      proteins using HAM/TSP IgG revealed two core epitopes within the C-terminal
      region of hnRNP A1. The first (aminoacids 191-SSQRGRSGSGNF-202), overlapped the
      RGG domain and the second (aminoacids 293-GQYFAKPRNQGG-304), with the M9
      shuttling sequence, two functionally important regions of hnRNP A1. Monoclonal
      antibodies to HTLV-1-tax also reacted with the epitopes. These data fulfill an
      important criterion of molecular mimicry, namely that mimicking epitopes are not
      random, but include biologically significant regions of target proteins. This
      suggests an important role for the cross-reactive immune response between HTLV-1
      and hnRNP A1 in the pathogenesis of immune-mediated neurological diseases via
      molecular mimicry.

PMID- 16600503
TI  - Oscillatory cortical activity during a motor task in a deafferented patient.
AB  - Little is known about the influence of the afferent peripheral feedback on the
      sensorimotor cortex activation. To answer this open question we investigated the
      alpha and beta band task-related spectral power decreases (TRPow) in the
      deafferented patient G.L. and compared the results to those of six healthy
      subjects. The patient has been deafferented up to the nose for 24 years but her
      motor fibers are unaffected and she can perform complex motor tasks under visual
      control. We recorded EEG (58 scalp positions) as well as the exerted force during
      a visuomotor task. The subjects had to maintain in precision grip an isometric
      force at 15% of the maximal voluntary contraction. In the patient we found a
      significantly higher alpha band spectral power during rest and larger alpha TRPow
      decreases during the motor task when compared to the healthy subjects' data. In
      contrast, we did not observe any significant differences between patient and
      controls for the beta band TRPow. The results indicate an altered functional
      alpha band network state in the patient, probably due to the chronic
      deafferentation leading to a deep 'idling' state of the contralateral
      sensorimotor area.

PMID- 16600504
TI  - Intragastric proteasome inhibition induces alpha-synuclein-immunopositive
      aggregations in neurons in the dorsal motor nucleus of the vagus in rats.
AB  - The neuropathological hallmark of idiopathic Parkinson's disease (PD) is
      dopaminergic neuron degeneration in the substantia nigra. However, it has been
      suggested that the neurodegenerative process initially may occur in the dorsal
      motor nucleus of the vagus (DMV). This implies that unidentified environmental
      toxins or neurotropic pathogens that is capable of passing the mucosal barrier of
      the gastrointestinal tract might affect the enteric nerve endings of the vagal
      neurons, possibly resulting in retrograde degeneration of the DMV. The present
      study aimed to evaluate the effects of proteasome inhibition of the intragastric
      nerve terminals of the DMV in rats. Following multiple injections of PSI, a
      selective proteasome inhibitor, or vehicle into the ventral wall of the stomach,
      the medulla oblongata was studied immunohistologically. In the DMV neurons of
      rats treated with PSI but not vehicle, alpha-synuclein-immunopositive
      intracytoplasmic inclusions and activated microglia were observed, predominantly
      in the left DMV. However, there was no significant loss of neurons. These results
      suggest that intragastric proteasome inhibition has a retrograde effect on DMV
      neurons but is insufficient to induce cell death, suggesting no causal linkage
      between inclusion body formation with proteasome inhibition and neuron death in
      the DMV. This might also implicate that Lewy body formation in the DMV in PD is
      possibly related to peroral invasion of environmental toxins that inhibit
      ubiquitin-proteasome system function.

PMID- 16600505
TI  - Increase in tyrosine phosphorylation of the NMDA receptor following the induction
      of status epilepticus.
AB  - The administration of lithium followed by pilocarpine induces status epilepticus
      (SE) that produces neurodegeneration and the subsequent development of
      spontaneous recurrent seizures. We have reported that tyrosine phosphorylation of
      the NMDA receptor is elevated over controls for several hours following 60 min of
      SE. In the current study, we assessed the temporal relationship between tyrosine
      phosphorylation of the NMDA receptor and the onset of SE. SE was induced using
      the Li/pilocarine model and phosphorylation of the NMDA receptor subunits NR2A
      and NR2B determined. Tyrosine phosphorylation of the NMDAR remained unchanged
      prior to the onset of SE and increased gradually thereafter. The onset of SE was
      accompanied by activation of Src-family tyrosine kinases and Pyk2 in the post
      synaptic density, consistent with a role for these enzymes in SE-induced tyrosine
      phosphorylation. The results indicate that tyrosine phosphorylation of the NMDAR
      closely parallels the activation of Src-family kinases and follows, rather than
      precedes, the onset of SE.

PMID- 16600506
TI  - Endogenous pain inhibitory systems activated by spatial summation are opioid
      mediated.
AB  - We previously developed a spatial summation model and demonstrated that spatial
      summation of pain involves the activation of both excitatory and inhibitory
      systems. The aim of this study was to determine whether the endogenous pain
      inhibitory systems recruited by the spatial summation model are opioid-mediated
      by verifying if they could be blocked by the opioid antagonist naloxone. Twenty
      healthy volunteers (10 men, 10 women) participated in a randomized, four-session,
      cross-over study. Each session consisted of pain perception ratings (visual
      analog scale) taken during the immersion of different surfaces of the arm in
      circulating noxious cold water (12 degrees C). The arm was arbitrarily divided
      into eight segments from fingertips to shoulder. Two sessions were increasing
      (from fingertips to shoulder) and two sessions were decreasing (from shoulder to
      fingertips). All sessions consisted of eight consecutive 2-min immersions
      separated by 5-min resting periods. Intravenous injections of naloxone
      hydrochloride (0.14 mg/kg) or saline (NaCl, 0.9%) were administered under double
      blind conditions. We found that during the control session (saline injection)
      there was a significant difference in pain intensity ratings between the
      increasing and decreasing sessions. The decreasing session resulted in lower pain
      intensity. As previously demonstrated, this lowering of the perception curve
      seems to be due to a large recruitment of inhibitory systems at the beginning of
      the decreasing session as opposed to a gradual recruitment during the increasing
      session. However, during the opioid inhibition session (naloxone injection) no
      differences were found between the increasing and decreasing sessions. Naloxone
      inhibited the endogenous pain inhibitory systems activated by the spatial
      summation model, suggesting that these systems have an opioid-mediated component,
      as previously reported for diffuse noxious inhibitory controls.

PMID- 16600507
TI  - Patients with Ehlers Danlos syndrome and CRPS: a possible association?
AB  - Rare patients are left with chronic pain, vasodysregulation, and other symptoms
      that define complex regional pain syndrome (CRPS), after limb traumas. The
      predisposing factors are unknown. Genetic factors undoubtedly contribute, but
      have not yet been identified. We report four CRPS patients also diagnosed with
      the classical or hypermobility forms of Ehlers Danlos syndrome (EDS), inherited
      disorders of connective tissue. These patients had been diagnosed using standard
      diagnostic criteria for CRPS and for EDS. All had sustained joint injury; in
      three this had been surgically treated. The association of these two diagnoses
      leads us to hypothesize that EDS might contribute to the development of CRPS in
      one or more of the following ways: via stretch injury to nerves traversing
      hypermobile joints, increased fragility of nerve connective tissue, or nerve
      trauma from more frequent surgery. We review the clinical presentation of the
      different Ehlers Danlos syndromes and provide clinical criteria that can be used
      to screen CRPS patients for EDS for clinical or research purposes.

PMID- 16600508
TI  - A comparative study of oxycodone and morphine in a multi-modal, tissue
      differentiated experimental pain model.
AB  - Visceral pain can be difficult to treat with classical mu-opioid agonists and it
      has been suggested to use opioids with distinct pharmacological profiles. In
      animal experiments, oxycodone has shown different effects compared to morphine,
      and clinical observations have shown that oxycodone may occasionally be superior
      to, e.g., morphine in the treatment of visceral pain. In the current study, we
      randomised 24 healthy subjects to treatment with either morphine (30 mg),
      oxycodone (15 mg) or placebo in a crossover study. The experimental pain model
      involved multi-modal (mechanical, thermal and electrical) pain tests in the skin,
      muscles and viscera. The pain tests were carried out at baseline and 30, 60 and
      90 min after oral administration of the drugs. The model showed effect of the two
      opioids compared to placebo on all stimulus modalities in all three types of
      tissues (all P values <0.001). Both opioids attenuated the sensory response
      mainly to painful stimulations. Morphine and oxycodone were equipotent in pain
      modulation of the skin and muscles, but oxycodone had superior analgesic effect
      to both morphine and placebo on the mechanical (P<0.001) and thermal (P<0.001)
      stimulations of the oesophagus. In conclusion, the multi-modal and tissue
      differentiated pain model could link findings from animal experiments to clinical
      findings. A different pharmacological profile of oxycodone compared to that of
      morphine was shown, and thus oxycodone may be a useful alternative to morphine in
      the treatment of visceral pain syndromes.

PMID- 16600510
TI  - Trichuris suis population dynamics following a primary experimental infection.
AB  - Trichuris suis population kinetics was studied by experimentally infecting 40
      pigs with 5000 T. suis infective eggs. Six pigs were sacrificed every 2 weeks
      from 1 to 9 weeks post-inoculation (p.i.) and the remaining 10 pigs were
      sacrificed 11 weeks p.i. to estimate worm burdens. An equal number of uninfected
      control pigs were sacrificed at the same time points for comparison. Egg
      excretions from each pig were evaluated every week from 5 to 11 weeks p.i.
      Peripheral blood eosinophilia and basophilia were also evaluated every 2 weeks
      throughout the experimental period. After an initial almost 100% establishment of
      T. suis an expulsion phase followed approximately 9 weeks p.i., resulting in an
      aggregated distribution of the worms in the pig population, as it is
      characteristic for most helminth infections. By 11 weeks p.i. almost all worms
      had been expelled. Egg excretion peaked 7 weeks p.i. and a significant non-linear
      relationship between worm burdens and egg excretion was found. The predilection
      site for T. suis was the caecum and proximal colon and the relative distribution
      of worms in the large intestine did not change over time until expulsion. Peaking
      peripheral blood eosinophil and basophil levels were observed in the T. suis
      infected pigs 5 and 7 weeks p.i., respectively, reflecting the host activated
      immune response against the parasite. We here describe the course of a primary T.
      suis infection in pigs by detailed worm counts, demonstrating an effective
      expulsion that results in an almost 100% clearance of infection as previously
      indicated by monitoring faecal egg excretion.

PMID- 16600511
TI  - Purification and characterization of a galactose-specific lectin with mitogenic
      activity from pinto beans.
AB  - A galactose-specific dimeric lectin from pinto beans was purified using a
      procedure that involved affinity chromatography on Affi-gel blue gel, anion
      exchange chromatography on Q-Sepharose, fast protein liquid chromatography (FPLC)
      ion exchange chromatography on Mono S, and FPLC-gel filtration on Superdex 200.
      The molecular mass of this homodimeric lectin was 62 kDa and that of each of its
      subunits was 31 kDa. The hemagglutinating activity of pinto bean lectin was
      stable within the pH range of 3-12 and the temperature range of 0-70 degrees C.
      By using the [3H-methyl]-thymidine incorporation assay, it was shown that the
      lectin had the ability to evoke a mitogenic response from murine splenocytes but
      it did not inhibit proliferation of L1210 leukemia cells. The pinto bean lectin
      inhibited HIV-1 reverse transcriptase with an IC50 of 3 microM.

PMID- 16600512
TI  - Double dissociation in the neural substrates of acute opiate dependence as
      measured by withdrawal-potentiated startle.
AB  - The basolateral amygdala and portions of the "extended" amygdala (i.e. central
      nucleus of the amygdala, bed nucleus of the stria terminalis and shell of the
      nucleus accumbens) have been implicated in the aversive aspects of withdrawal
      from chronic opiate administration. Given that similar withdrawal signs are
      observed following a single opiate exposure, these structures may also play a
      role in "acute opiate dependence." In the current study, drug-naive rats
      underwent naloxone-precipitated withdrawal from acute morphine (10 mg/kg)
      exposure on two successive days. On either the first or second day of testing,
      the basolateral amygdala, central nucleus of the amygdala, bed nucleus of the
      stria terminalis, or nucleus accumbens was temporarily inactivated immediately
      prior to naloxone injection by microinfusion of the glutamatergic alpha-amino-3
      hydroxy-5-methyl-4-isoxazole proprionic acid receptor antagonist 1,2,3,4
      tetrahydro-6-nitro-2,3-dioxo-benzo(f)quinoxaline-7-sulfonamide (3 microg/0.5
      microl). On the first day, inactivation of the basolateral amygdala, central
      nucleus of the amygdala, or bed nucleus of the stria terminalis, but not the
      nucleus accumbens blocked withdrawal-potentiated startle, a behavioral measure of
      the anxiogenic effects of withdrawal. On the second day, inactivation of the
      nucleus accumbens, but not the basolateral amygdala, central nucleus of the
      amygdala, or bed nucleus of the stria terminalis disrupted the withdrawal effect.
      Effects of structural inactivations on withdrawal-potentiated startle were not
      influenced by differences in withdrawal severity on the two days of testing. A
      fear-potentiated startle procedure provided functional confirmation of correct
      cannulae placement in basolateral amygdale- and central nucleus of the amygdala
      implanted animals. Our findings indicate a double dissociation in the neural
      substrates of withdrawal-potentiated startle following a first versus second
      morphine exposure, and may reflect a reorganization of the neural circuitry
      underlying the expression of withdrawal-induced negative affect during the
      earliest stages of opiate dependence.

PMID- 16600513
TI  - C-type natriuretic peptide modulates glutamate receptors on cultured rat retinal
      amacrine cells.
AB  - C-type natriuretic peptide, widely distributed in the CNS, may work as a
      neuromodulator. In this work, we investigated modulation by C-type natriuretic
      peptide of functional properties of glutamate receptors in rat retinal GABAergic
      amacrine cells in culture. Immunocytochemical data revealed that natriuretic
      peptide receptor-B was strongly expressed on the membrane of cultured GABAergic
      amacrine cells. By whole cell recording techniques we further identified the
      glutamate receptor expressed on the GABAergic amacrine cells as an AMPA
      preferring subtype. Incubation with C-type natriuretic peptide suppressed the
      AMPA receptor-mediated current of these cells in a dose-dependent manner by
      decreasing the efficacy and apparent affinity for glutamate. The effect of C-type
      natriuretic peptide was reversed by HS-142-1, a guanylyl cyclase-coupled
      natriuretic peptide receptor-A/B antagonist. Meanwhile, the selective natriuretic
      peptide receptor-C agonist cANF did not change the glutamate current. In
      conjunction with the immunocytochemical data, these results suggest that the C
      type natriuretic peptide effect may be mediated by natriuretic peptide receptor
      B. Furthermore, incubation of retinal cultures in the C-type natriuretic peptide
      containing medium elevated cGMP immunoreactivity in the GABAergic amacrine cells,
      and the C-type natriuretic peptide effect on the glutamate current was mimicked
      by application of 8-Br-cGMP. It is therefore concluded that C-type natriuretic
      peptide may modulate the glutamate current by increasing the intracellular
      concentration of cGMP in these cells via activation of natriuretic peptide
      receptor-B.

PMID- 16600514
TI  - Fatty acids differentially affect serotonin receptor and transporter binding in
      the rat brain.
AB  - The aim of this study was to examine the influence of different fat diets on
      serotonin receptor and transporter binding. Male Sprague-Dawley rats were fed a
      diet of either high saturated fat, omega-6 polyunsaturated fatty acid, omega-3
      polyunsaturated fatty acid or low fat (control) for eight weeks. Using Beta
      Imager quantification techniques, [(3)H]ketanserin, [(3)H]mesulergine and
      [(3)H]paroxetine binding to serotonin (5-HT)(2A), 5-HT(2C) receptors and 5-HT
      transporters (5-HTT) was measured throughout the brain in all four groups. All
      three high fatty acid diets influenced serotonin receptor binding, however the
      most pronounced effects were that compared with the low fat control group, i) 5
      HT(2A) receptor binding was increased in the caudate putamen, but reduced in the
      mammillary nucleus in high saturated fat and high omega-6 polyunsaturated fatty
      acid diet groups; ii) 5-HT(2C) receptor binding was reduced in the mamillary
      nucleus of saturated fat group and reduced in prefrontal cortex of the omega-6
      polyunsaturated fatty acid and omega-3 polyunsaturated fatty acid groups; and
      iii) 5-HTT binding was reduced in the hippocampus in the omega-6 polyunsaturated
      fatty acid group. Overall, the omega-6 polyunsaturated fatty acid diet exerted
      the most influence on serotonin receptor and transporter binding. These results
      may be of importance in relation to neuropsychiatric diseases such as
      schizophrenia, where associations between altered fatty acid levels and the
      serotonergic system have been made.

PMID- 16600515
TI  - Chronic restraint stress induces changes in synapse morphology in stratum
      lacunosum-moleculare CA1 rat hippocampus: a stereological and three-dimensional
      ultrastructural study.
AB  - Chronic restraint stress is known to affect the morphology and synaptic
      organization of the hippocampus, predominantly within CA3 but also in CA1 and
      dentate gyrus. In this study, we provide the first evidence for specific
      ultrastructural alterations affecting asymmetric axo-spinous synapses in CA1
      stratum lacunosum-moleculare following chronic restraint stress (6 h/day, 21
      days) in the rat. The structure of asymmetric axo-spinous post-synaptic densities
      was investigated using serial section three-dimensional reconstruction procedures
      in control (n=4) and chronic restraint stress (n=3) animals. Dendritic spine
      profiles (spine head+neck) associated with the sampled synaptic contacts (30 per
      animal) were also reconstructed in three-dimensions. Morphometric analyses
      revealed a significant increase in post-synaptic density surface area (+36%;
      P=0.03) and a highly significant increase in post-synaptic density volume (+79%;
      P=0.003) in the chronic restraint stress group. These changes were directly
      associated with 'non-macular' (perforated, complex and segmented) post-synaptic
      densities. A highly significant overall increase in the 'post-synaptic density
      surface area/spine surface area' ratio was also detected in the chronic restraint
      stress group (+27%; P=0.002). In contrast, no quantitative changes in spine
      parameters were found between groups. The Cavalieri method was used to assess the
      effects of chronic restraint stress exposure upon CA1 hippocampal volume. The
      mean volume of total dorsal anterior CA1 hippocampus was significantly lower in
      the chronic restraint stress group (-16%; P=0.036). However, when corrected for
      volume changes, no significant alteration in a relative estimate of the mean
      number of asymmetric axo-spinous synapses was detected in CA1 stratum lacunosum
      moleculare between control and chronic restraint stress groups. The data indicate
      a structural remodeling of excitatory axo-spinous synaptic connectivity in rat
      CA1 stratum lacunosum-moleculare as a result of chronic restraint stress.

PMID- 16600516
TI  - How many types of cholinergic sympathetic neuron are there in the rat stellate
      ganglion?
AB  - Sympathetic cholinergic postganglionic neurons are present in many sympathetic
      ganglia. Three classes of sympathetic cholinergic neuron have been reported in
      mammals; sudomotor neurons, vasodilator neurons and neurons innervating the
      periosteum. We have examined thoracic sympathetic ganglia in rats to determine if
      any other classes of cholinergic neurons exist. We could identify cholinergic
      sudomotor neurons and neurons innervating the rib periosteum, but confirmed that
      cholinergic sympathetic vasodilator neurons are absent in this species. Sudomotor
      neurons contained vasoactive intestinal peptide (VIP) and calcitonin gene-related
      peptide (CGRP) and always lacked calbindin. Cholinergic neurons innervating the
      periosteum contained VIP and sometimes calbindin, but always lacked CGRP.
      Cholinergic neurons innervating the periosteum were usually surrounded by
      terminals immunoreactive for CGRP. We conclude that if any undiscovered
      populations of cholinergic neurons exist in the rat thoracic sympathetic chain,
      then they are indistinguishable in size, neurochemistry and inputs from sudomotor
      or cholinergic neurons innervating the periosteum. It may be that the latter two
      populations account for all cholinergic neurons in the rat thoracic sympathetic
      chain ganglia.

PMID- 16600517
TI  - Ketamine affects memory consolidation: differential effects in T-maze and passive
      avoidance paradigms in mice.
AB  - The effects of ketamine, an N-methyl-D-aspartate (NMDA) antagonist, on memory in
      animals have been limited to the sub-anesthetic dose given prior to training in
      previous studies. We evaluated the effects of post-training anesthetic doses of
      ketamine to selectively manipulate memory consolidation, and the effect of pre
      retention sub-anesthetic doses of ketamine on memory retrieval in passive
      avoidance and T-maze tasks in mice. Repeated post-training anesthetic doses of
      ketamine impaired the consolidation of memory in the T-maze but not in passive
      avoidance paradigms. This impairment was not permanent but diminished 1-2 days
      after ketamine withdrawal. Sub-anesthetic post-training doses of ketamine (5
      mg/kg) had no effect on memory consolidation, and larger doses (10, 20 and 50
      mg/kg) did not influence the retrieval of memory in the T-maze. The data suggest
      that repeated anesthetic doses of ketamine block NMDA receptors and affect memory
      consolidation. Moreover, NMDA mechanisms antagonized by ketamine appear to be
      selectively involved in spatial (T-maze) memory mechanisms but may not be
      necessary for non-spatial (passive avoidance) memory consolidation.

PMID- 16600518
TI  - Valproic acid induces caspase 3-mediated apoptosis in microglial cells.
AB  - Valproic acid is widely used for the treatment of epilepsy and mood disorders,
      but its mode of action is unclear. Treatment of neuronal cells with valproic acid
      promotes neurite sprouting, is neuroprotective and drives neurogenesis; however
      its effects on non-neuronal brain cells are less clear. We report that valproic
      acid induces apoptosis in the mouse microglial cell line, BV-2, at concentrations
      within the therapeutic range. When BV-2 cells were incubated for 24 h with 500
      1000 microM valproic acid we observed a reduction in cell number, the appearance
      of apoptotic morphology and increased caspase 3 cleavage. Exposure of a
      macrophage cell line (RAW 264.7) to similar concentrations of valproic acid also
      led to reduced cell number but no caspase 3 cleavage, suggesting these cells
      responded to valproic acid with reduced proliferation rather than apoptosis. This
      was confirmed using bromodeoxyuridine incorporation studies. Similar
      concentrations of valproic acid added to Neuro-2a, SK-N-SH and C6 cell lines as
      well as human NTera-2 astrocytes did not evoke cell death. The caspase 3
      inhibitor DEVD-CHO inhibited valproic acid-induced apoptosis in BV-2 cells
      whereas the MEK inhibitor U0126 potentiated valproic acid-mediated apoptosis.
      These results demonstrate that valproic acid selectively induces apoptosis in BV
      2 cells by way of a caspase 3-mediated action. As activated microglia secrete
      neurotoxins in neurodegenerative diseases such as Alzheimer's, Parkinson's, and
      HIV dementia, valproic acid may alleviate these diseases by selectively killing
      microglia.

PMID- 16600519
TI  - Serotonergic and nonserotonergic neurons in the dorsal raphe nucleus send
      collateralized projections to both the vestibular nuclei and the central
      amygdaloid nucleus.
AB  - Using a combination of double retrograde tracing and serotonin immunofluorescence
      staining, we examined whether individual serotonergic and nonserotonergic neurons
      in the dorsal raphe nucleus are sources of collateralized axonal projections to
      vestibular nuclei and the central amygdaloid nucleus in the rat. Following
      unilateral injections of Diamidino Yellow into the vestibular nuclei and Fast
      Blue into the central amygdaloid nucleus, it was observed that approximately one
      fourth of the dorsal raphe nucleus neurons projecting to the vestibular nuclei
      send axon collaterals to the central amygdaloid nucleus. Immunofluorescence
      staining for serotonin revealed that more than half of the dorsal raphe nucleus
      neurons from which these collateralized projections arise contain serotonin-like
      immunoreactivity. These findings indicate that a subpopulation of serotonergic
      and nonserotonergic dorsal raphe nucleus cells may act to co-modulate processing
      in the vestibular nuclei and the central amygdaloid nucleus, regions implicated
      in the generation of emotional and affective responses to real and perceived
      motion.

PMID- 16600520
TI  - Role of astrocytic S100beta in behavioral hypersensitivity in rodent models of
      neuropathic pain.
AB  - S100beta is a calcium-binding peptide produced mainly by astrocytes that exerts
      paracrine and autocrine effects on neurons and glia. We have previously shown
      that S100beta is markedly elevated at the mRNA level in the spinal cord following
      peripheral inflammation, intraplantar administration of complete Freund's
      adjuvant in the rat. The purpose of the present study was to further investigate
      the role of astrocytic S100beta in mediating behavioral hypersensitivity in
      rodent models of persistent pain. First, we assessed the lumbar spinal cord
      expression of S100beta at the mRNA and protein level using real-time RT-PCR,
      Western blot and immunohistochemistry analysis following L5 spinal nerve
      transection in rats, a rodent model of neuropathic pain. Second, we assessed
      behavioral hypersensitivity (mechanical allodynia) in wild type and genetically
      modified mice lacking or overexpressing S100beta following L5 spinal nerve
      transection. Third, we assessed the expression level of S100beta protein in the
      CD1 wild type mice after nerve injury. We report that lumbar spinal S100beta mRNA
      steadily increased from days 4-28 after nerve injury. S100beta protein in the
      lumbar spinal cord was significantly increased in both rats and mice at day 14
      following nerve injury as compared with sham control groups. S100beta genetically
      deficient mice displayed significantly increased tactile thresholds (reduced
      response to non-noxious stimuli) after nerve injury as compared with the wild
      type group. S100beta overexpressing mice displayed significantly decreased
      tactile threshold responses (enhanced response to non-noxious stimuli). Together,
      these results from both series of experiments using a peripheral nerve injury
      model in two different species implicate the involvement of glial-derived
      S100beta in the pathophysiology of neuropathic pain.

PMID- 16600521
TI  - Distinct roles for spinophilin and neurabin in dopamine-mediated plasticity.
AB  - Protein phosphatase 1 plays a major role in the governance of excitatory synaptic
      activity, and is subject to control via the neuromodulatory actions of dopamine.
      Mechanisms involved in regulating protein phosphatase 1 activity include
      interactions with the structurally related cytoskeletal elements spinophilin and
      neurabin, synaptic scaffolding proteins that are highly enriched in dendritic
      spines. The requirement for these proteins in dopamine-related neuromodulation
      was tested using knockout mice. Dopamine D1-mediated regulation of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionate receptor activity was deficient in both
      striatal and prefrontal cortical neurons from neurabin knockout mice; in
      spinophilin knockout mice this deficit was manifest only in striatal neurons. At
      corticostriatal synapses long-term potentiation was deficient in neurabin
      knockout mice, but not in spinophilin knockout mice, and was rescued by a D1
      receptor agonist. In contrast, long-term depression was deficient in spinophilin
      knockout mice but not in neurabin knockout mice, and was rescued by D2 receptor
      activation. Spontaneous excitatory post-synaptic current frequency was increased
      in neurabin knockout mice, but not in spinophilin knockout mice, and this effect
      was normalized by D2 receptor agonist application. Both knockout strains
      displayed increased induction of GluR1 Ser(845) phosphorylation in response to D1
      receptor stimulation in slices, and also displayed enhanced locomotor activation
      in response to cocaine administration. These effects could be dissociated from
      cocaine reward, which was enhanced only in spinophilin knockout mice, and was
      accompanied by increased immediate early gene induction. These data establish a
      requirement for synaptic scaffolding in dopamine-mediated responses, and further
      indicate that spinophilin and neurabin play distinct roles in dopaminergic signal
      transduction and psychostimulant response.

PMID- 16600522
TI  - Can home smoking restrictions influence adolescents' smoking behaviors if their
      parents and friends smoke?
AB  - Research suggests that the presence of a total ban on smoking in the home is
      associated with a reduced likelihood of tobacco experimentation among
      adolescents. While the influence of parental smoking on this association is
      examined in this work, no study has examined the influence of friends' smoking
      behavior. In this study, we use data from a statewide survey of students (n=4125)
      from the Australian State of Victoria to examine the association between home
      smoking bans and stage of smoking uptake after controlling for parental smoking
      and smoking among friends. Logistic regression revealed that students residing in
      homes with a total ban on smoking were least likely to be susceptible to smoking
      or to have experimented with smoking. While there was an interaction between
      parental smoking status and home bans on smoking uptake stage, indicating that
      the effect of home bans was strongest when neither parent smoked, there was no
      interaction between home bans and friends' smoking. The results suggest that home
      smoking bans reduce the likelihood of an adolescent trying tobacco regardless of
      their friends' smoking behavior. By adopting strong home smoking bans, parents
      can reduce some of the influence friends' smoking can have on the smoking
      behavior of their adolescent.

PMID- 16600523
TI  - Drinking game participation among college students: gender and ethnic
      implications.
AB  - Participation in drinking games by college students has recently sparked research
      attention. While previous research indicates that women play drinking games at
      lower frequencies than men, the current study reveals that college women may be
      playing games at rates similar to college men. In a sample of 105 coed college
      students, participants completed a 3-month Timeline Followback recording every
      drinking event and quantity consumed. They then were prompted to identify which
      drinking events involved drinking games and how much alcohol was consumed during
      game playing. Both men and women engaged in drinking games at similar rates and
      consumed more drinks on game playing days than on non-game drinking days.
      However, drinking game participation was related to alcohol-related consequences
      in women only. Further, while Caucasian participants played drinking games more
      often than non-Caucasian participants, an association between game participation
      and alcohol-related consequences emerged in non-Caucasian participants.

PMID- 16600524
TI  - Cell brain: insight into hepatocarcinogenesis.
AB  - Although great effort has been made, the understanding of the mechanisms of
      hepatocarcinogenesis is still limited. Among all the related hypotheses, the cell
      brain theory, which emphasized the integrate roles of the complex consisting of
      centrosome, the embedded centrioles and connecting microtubules (MTs) and
      interpreted cancer as a cell brain illness rather than a genetic disease, emerges
      to be more logic and recognizable. According to cell brain theory, all the
      cellular procedures are coordinated as a whole by the "brain" of a cell
      determining a cell's fate. Structural and functional abnormalities in the cell
      brain may result in unequal or multipolar segregation of the chromosomes, thereby
      causing cell cycle disorder, centrosome amplification, and genomic instability.
      Although there lacking of direct evidence associating cell brain defects and
      hepatocarcinogenesis, latest understanding of the roles of the cells brain in
      cell control does teach us that any defects in the cell brain may contribute to
      hepatocarcinogenesis. Briefly, more than 100 key proteins involved in DNA
      synthesis, DNA repair, cell cycle, and apoptosis have been localized to the cell
      brain. Specifically, more and more novel proteins associated with centrosome such
      as centrin, centriolin and cenexin are located in the centriole, a core component
      of cenrtrosome. Aberrant phosphorylation of these proteins and/or mutation of the
      coding genes may inevitably cause supernumerary centrioles and/or excess
      pericentriolar material. Modifications of any MT proteins such as tyrosinated
      tubulin (Tyr-tubulin), detyrosinated tubulin (Glu-tubulin) and Delta2-tubulin may
      change the structure and function of MTs, thereby interfering with G1 phase
      progression, altering the dynamics of some key proteins, and mis-regulating
      signal transduction and transcription. Although little work has been done, we
      intend to believe, based on the latest understanding of the novel roles of the
      cell brain in cell control, that defects in any part of the cell brain either in
      the structure or in the function may result in changes of the genes, eventually
      leading to the development of liver cancer, which is discussed in this paper and
      is expected to be helpful in shedding light on the often paradoxical observations
      seen in the development of cancer, including HCC. It also teaches us that when
      treating cancerous problems therapeutically or prophylactically, great attention
      should be given to the centrosome/cell brain, instead of gene alone. More
      specifically, the centrosome-centered cell brain may come to be novel targets in
      the treatment of cancer including HCC.

PMID- 16600525
TI  - Does adenosine deaminase play a key role in coronary artery disease.
AB  - Adenosine deaminase (ADA) is an enzyme which catalyzes adenosine to inosine.
      Patients who inherently lack the enzyme have defects in both humoral and cellular
      immunity. ADA plays an important role in many immunity mediate diseases, such as
      asthma, Graves' disease and tuberculosis. Coronary artery disease (CAD) has been
      considered as an inflammatory and immunizing disease recently. However, there are
      few reports about the effect of ADA in cardiovascular fields. In fact, ADA may
      play a key role in the immunity, inflammation and other aspects of CAD. This
      hypothesis is potentially based on three aspects of evolution. First, ADA
      inhibitors attenuate the elevation of proinflammatory factors, which shows ADA
      mediate in the inflammation response. ADA also has effect on the activation of
      complement system by the deamination of adenosine. Thus, ADA has a role in CAD by
      affecting inflammation process. Second, many effects produced by ADA are caused
      by the metabolism of adenosine. It is known that adenosine can inhibit the
      invasion of the neutrophil so as to attenuate the ischemic/reperfusion injury .
      Adenosine can increase coronary artery blood flow during active stress and
      hypoxia to balance the oxygen supply and demand. Adenosine can also account for
      the majority of basal vascular endothelial growth factor (VEGF) mRNA and protein
      expression in cultured myocardial vascular smooth muscle cells under normoxic
      conditions to stimulate the angiogenesis. If adenosine is rapidly metabolized by
      the high level of ADA, the advantages of adenosine will lost. Finally, adenosine
      is catalyzed to inosine, which can produce superoxide radicals and exaggerate the
      ischemic/reperfusion injury. In conclusion ADA can have a crucial role in CAD, if
      design and development of therapeutic strategies against ADA is guaranteed, an
      innovational therapeutic approach to CAD can be realized.

PMID- 16600526
TI  - Origin of segmentation in the human structure.
AB  - Crystallographic analysis of biological and non-biological minerals does not
      reveal any significant differences between the two, which is indicative of common
      crystallization processes. It can be supposed that the human organism is a
      biocrystalloid in a sense that it is regarded both at the level of the whole
      organism and individual cells as a composite entity consisting of a crystal-like
      structure and pericrystalline medium. A similarity can be found between the
      growing layer of a crystal in the crystal-forming medium and a cell structure
      with liquid washing it. A mineral organism therefore can be regarded as the
      active superficial part of a crystal taken together with pericrystalline crystal
      forming medium which controls crystal growth and modifies the system depending on
      the structure of the growing system. Aggregation is one of the fundamental
      features of minerals as they are found primarily not only as separate objects but
      also as aggregates, i.e. regular cohesive masses or synmineralogical systems.
      Ability to aggregation in an orderly way is expressed as self-organization. This
      feature is inherent not only to compound molecules but also to associates of a
      higher order. The cell biology has shown that when similar cells touch each other
      they tend to cohere forming aggregates characteristic of the given cell
      population. Similar live systems and their components that perform the same
      function have an ability to integrate and form firstly a conglomerate (colony)
      and then an organism. Integration explains association of multi-segmented
      entities into a single organism and the resulting structure would consists of the
      two groups of segments, i.e. appearance of an organism consisting of two
      different but of the same type specimens, each of which had different number of
      segments. Phylogenetically, an early precursor of the man evolved from a simple
      cell into an integrated multi-segment organism through several stages--initially
      a simple cell, then a cell colony, then a single-segment organism, then an
      organism like a concave ball, then a colony of one-segment multicellular
      organisms and finally a multi-segment multicellular organism. Integration of five
      and eight-segment organisms resulted in the formation of a 13-segment precursor
      organism of man. Segmentation is nothing else but traces of boundaries left
      following integration of separate multicellular non-segmented specimens with
      gradual fading of their differences and formation of a new entity in compliance
      with formation laws.

PMID- 16600527
TI  - Uncertainty in descriptions of biosocial phenomena and the schism between
      preventionists and moralists.
AB  - Biosocial systems are dual-natured phenomena. A relationship between social and
      biological parameters of any biosocial system may be described by an uncertainty
      principle: it is not possible to measure both types of parameters exactly and
      simultaneously. A full description of dual-natured phenomenon requires two
      mutually exclusive (complementary) concepts. Preventionists and moralists use
      complementary descriptions of HIV/AIDS epidemic, sexual behavior and drug
      addiction. That is why they do not understand each other. The "compromise" may be
      defined as taking into consideration both types of descriptions. The compromise
      determines approximate values of complementary sets of parameters somewhere
      between their extreme alternative or complementary descriptions. A compromise is
      reached within the framework of the complex interplay of complementary
      descriptions and currently existing norms and generates new social norms and new
      intersectoral partnerships. The existing schism between preventionists and
      moralists concerning HIV/AIDS and similar issues is a result of uncertainty of
      complementary descriptions of complex biosocial systems and should be resolved
      through compromises which may vary in different countries.

PMID- 16600528
TI  - Employment experience in relation to alcohol, tobacco, and betel nut use among
      youth in Taiwan.
AB  - The aim of this study is to assess the association linking employment experience
      with alcohol, tobacco, and betel nut involvement among youth in Taiwan. In 2004,
      an outreach program was conducted during weekdays to recruit youth sample in
      seven major geographic regions. A total of 5886 youth aged 12-18 years drawn from
      26 cities or towns were assessed by a two-page anonymous self-administered
      questionnaire, including sociodemographic characteristics, employment-,
      development-, and drug-related experiences. In Taiwan, youthful experience of
      alcohol, tobacco, and polydrug use varies by employment status, work intensity,
      and job type. Holding a full-time job and working in certain settings (e.g.,
      grocery, restaurants) were found associated with an excess of drug-using
      behaviors. With taking age, male gender, family context, disposable allowance,
      and school attendance into account, working youths were two to four times as
      likely to have recent drug involvement than their non-working counterparts,
      especially for tobacco and polydrug (OR=3.32, 95% CI: 2.58-4.27, p<0.001;
      OR=3.76, 95% CI: 2.76-5.13, p<0.001). Youths in the labor force emerge as a
      subgroup experiencing greater use of alcohol, tobacco, betel nut, and polydrug.
      Future prevention programs may target this high-risk group to reduce possible
      drug-related negative consequences in developmental and health domains in Taiwan.

PMID- 16600529
TI  - Racial differences in marijuana-users' risk of arrest in the United States.
AB  - A recent study of arrest data show that African Americans are 2.5 times more
      likely to be arrested for marijuana possession offences than Whites, even though
      general prevalence estimates show that they are no more likely to be using. The
      current study investigates the purchase patterns of marijuana users from the 2002
      National Survey on Drug Use and Health (NSDUH) to evaluate whether differences in
      purchasing behaviors exist across racial groups. Although in general people who
      purchase marijuana are more likely to buy in private settings and from someone
      they know, this analysis shows that African Americans are statistically more
      likely to engage in risky purchasing behaviors that increase their likelihood of
      arrest. Using trivariate probit regression with demographic, drug use, and drug
      market covariates, analyses reveal that African Americans are nearly twice as
      likely to buy outdoors (0.31 versus 0.14), three times more likely to buy from a
      stranger (0.30 versus 0.09), and significantly more likely to buy away from their
      homes (0.61 versus 0.48). These results provide an additional explanation for the
      differential in arrest rates between African Americans and Whites.

PMID- 16600530
TI  - Polymorphisms of alcohol-metabolizing enzymes and the risk for alcoholism and
      alcoholic liver disease in Caucasian Spanish women.
AB  - BACKGROUND: The relationship of polymorphisms of the genes that encode for
      alcohol-metabolizing enzymes and individual vulnerability to alcoholism and
      alcoholic liver disease (ALD) in women is unclear. We determined the genotypes of
      ADH1B, ADH1C, CYP2E1 (Dra-I and Pst-I) and ALDH2 in a group of Caucasian Spanish
      women. METHODS: We performed a cross-sectional case-control study. The study
      group was made of 220 women. Of these, 85 were alcoholic (27 without liver
      disease and 58 with alcoholic liver disease) and 135 were non-alcoholic (42
      healthy controls and 93 with liver disease unrelated to alcohol). Genotyping of
      alcohol-metabolizing enzymes was performed using PCR-RFLP methods. RESULTS: The
      distribution of the allelic variants (alleles 1 and 2) in the whole subjects
      analyzed was: ADH1B 91.6% and 8.4%; ADH1C 58.4% and 41.6%; CYP2E1 Dra-I 15% and
      85%; CYP2E1 Pst-I 96.8% and 3.2%; and ALDH2 100% and 0%, respectively. Carriage
      of genotypes containing the ADH1B*2 mutant allele significantly protected against
      alcoholism [odds-ratio (OR)=0.00; 95% confidence interval (95% CI): 0.00-0.94;
      p=0.02] but was associated with an increased risk for alcoholic liver disease
      among alcohol-dependent women [OR=0.43; 95% CI: 0.18-0.41; p=0.004]. Analysis of
      the remaining loci showed no significant associations. CONCLUSIONS: In Caucasian
      Spanish women the ADH1B*2 allele modulates the risk for alcohol dependence and
      for alcoholic liver disease. Given the small number of alcoholic women analyzed
      here, these data need further validation in larger cohorts.

PMID- 16600531
TI  - Effects of plasmin on sperm-oocyte interactions during in vitro fertilization in
      the pig.
AB  - The present study was undertaken to examine the effect of plasmin on sperm
      viability and sperm-oocyte interaction during in vitro fertilization in the pig.
      Porcine sperm, which were washed in Dulbecco's PBS were re-suspended and
      incubated in fertilization medium (mTBM; modified Tris-buffered medium)
      containing 0, 0.1, 1.0, 10.0 or 100.0ng/mL of plasmin. Sperm viability was not
      affected by plasmin treatment. Addition of plasmin in doses ranging from 0.1 to
      100.0ng/mL for 2, 4 or 6h to washed boar sperm resulted in enhancement of
      acrosome reaction (AR) compared with untreated cells. The concentration of
      0.1ng/mL plasmin (95+/-18 sperm/oocyte) had no effect on sperm binding, whereas
      1.0ng/mL (123+/-21 sperm/oocyte), 10.0ng/mL (124+/-16 sperm/oocyte) and
      100.0ng/mL (124+/-15 sperm/oocyte) of plasmin increased sperm binding compared
      with the control (83+/-15 sperm/oocyte). The zona pellucida solubility (zona
      dissolution time) was less in medium with 1.0ng/mL (123+/-24s), 10.0ng/mL (99+/
      15s) or 100.0ng/mL (95+/-19s) plasmin compared with control (176+/-27s). When pig
      oocytes and sperm were co-incubated in various concentrations of plasmin for 6h,
      the penetration rate was greater in medium with 1.0ng/mL plasmin (77.5+/-3.1%)
      compared with the control. However, there were no differences in the polyspermic
      rates and mean number of sperm (MNS)/oocyte between the groups treated with
      plasmin and control. These results suggest that plasmin might play a role in
      events related to fertilization.

PMID- 16600532
TI  - The postpartum buffalo: I. Endocrinological changes and uterine involution.
AB  - To maintain a calving interval of 13-14 months in buffaloes, successful breeding
      must take place within 85-115 days after calving. Disturbances during this period
      due to delay of uterine involution or resumption of estrous activity are likely
      to prolong the calving interval and reduce the lifetime reproductive and
      productive efficiency. In this article literature on endocrinological changes in
      the peripartum period and on factors affecting uterine involution are reviewed.
      The available information indicated that although the availability of releasable
      FSH does not appear to be a limiting factor for resumption of postpartum
      cyclicity a substantial increase of releasable LH and replenishment of pituitary
      stores occurred around Day 20 in dairy and Day 30 in swamp buffaloes. There is
      evidence that follicular activity is resumed early (15-30 days) in the postpartum
      period. However, the factors which initiate release of appropriate LH pulses,
      follicular maturation and ovulation in the postpartum buffalo need further
      studies. The mean interval to complete uterine involution varied widely between
      19 and 52 days. Assessment of cervical and uterine horn diameters by rectal
      palpation alone is not satisfactory to diagnose delayed uterine involution and
      possible subclinical uterine infection. Vaginal inspection can be included as a
      fundamental part of postpartum genital examination for diagnosis of such case.
      Uterine involution, however, does not seem to be a limiting factor for
      achievement of satisfactory fertility in the postpartum buffalo but the main
      determinant is resumption of estrous activity.

PMID- 16600533
TI  - Effect of Bradykinin on Murrah buffalo (Bubalus bubalis) semen cryopreservation.
AB  - Keeping in view the poor freezability of bubaline semen in conventionally used
      extenders, this study was conducted on three Murrah bulls to improve semen
      cryopreservation with the incorporation of Bradykinin (0.5, 1.0 and 2.0 ng ml(
      1)) in routinely used egg yolk tris-glycerol (EYTG) extender. Bradykinin (2.0 ng
      ml(-1)) had significant (P<0.05) beneficial effect on live sperm % (81.6+/-1.8)
      and hypo osmotic swelling (HOS) % (63.0+/-1.3) as compared to their respective
      control values of 73.4+/-2.1 and 56.3+/-2.0 at 0 h post freezing. The post-thaw
      progressive sperm motility in semen samples diluted with EYTG containing 2.0 ng
      ml(-1) Bradykinin (65.5+/-1.4) was also significantly (P<0.01) higher than
      control (60.3+/-1.9) at 0 h post freezing. Thus incorporation of 2 ng ml(-1)
      Bradykinin in buffalo semen diluted in EYTG extender may be useful in improving
      the quality of cryopreserved bubaline semen.

PMID- 16600534
TI  - Design, synthesis and gene delivery efficiency of novel oligo-arginine-linked PEG
      lipids: effect of oligo-arginine length.
AB  - The design, synthesis, and evaluation of in vitro gene delivery efficacy of a
      novel series of oligo-Arg-lipid conjugates are described. 3,5
      Bis(dodecyloxy)benzamide (BDB) was employed as the lipid component, and a
      poly(ethylene glycol) (PEG) spacer was introduced between the C-terminal of oligo
      Arg and the amide group of BDB. Four derivatives with various oligo-Arg lengths
      (ArgN-PEG-BDB; N = 4, 6, 8, 10: the number of arginine residues) were prepared,
      and the effect of oligo-Arg length on the gene transfection was investigated in
      HeLa cells. Transfection efficiency increased as the number of arginine residues
      increased. Arg10-PEG-BDB showed the highest transfection efficiency, without
      severe toxicity to cells. These findings well corresponded to the cellular
      association of the Arg-PEG-BDB/DNA complex determined by flow cytometry. Even in
      the presence of serum, Arg10-PEG-BDB achieved appreciable cellular association
      and attained high gene expression. Thus, Arg10-PEG-BDB is potentially a simple
      and useful gene delivery tool, because one need only to mix it with plasmid DNA
      and apply the complexes to the cells even in a serum-containing medium.

PMID- 16600535
TI  - Cationic liposomes as potential carriers for ocular administration of peptides
      with anti-herpetic activity.
AB  - In the present study the preparation, characterization and activity of cationic
      liposomes containing the secretory form of herpes simplex virus type 1 (HSV-1)
      glycoprotein B (gB1s) or two related polylysine rich peptides, namely DTK1 and
      DTK2, were described. The immunotherapeutic potential of these HSV antigens
      containing liposomes was examined with a rabbit ocular model of HSV-1 infection.
      Our study indicates that the liposomes (i) are able to encapsulate quantitatively
      gB1s and around 30% the DTK peptides, (ii) are characterized by dimensions
      compatible with ocular applications and (iii) can release the peptide comparably
      to the free solution. In addition, neutralization studies demonstrated that an
      anti-DTK specific polyclonal antiserum can inhibit HSV-1 infection, indicating
      that such peptides could be a good immunogen/antigen in an anti-HSV vaccine
      formulation. Although the vaccination protocol did not induce protection against
      the eye disease, a significative protection against a lethal ocular challenge was
      detectable together with the absence of reactivation episodes from latency on the
      survived animals. In this respect, the use of cationic liposomes coupled to gB1s
      and DTK peptides, as a local ocular vaccine, could represent an interesting
      approach in order to obtain a possible efficacy in protecting animals against a
      subsequent HSV-1 ocular challenge.

PMID- 16600536
TI  - Analysis of the molecular interaction between mannosylated proteins and serum
      mannan-binding lectins.
AB  - The kinetics and specificity of the molecular interaction between proteins
      modified with varying numbers of mannose residues and isolated rabbit mannan
      binding lectin (MBL) were characterized by using surface plasmon resonance
      spectroscopy (SPR). Mannosylated bovine serum albumin (Man-BSA) with different
      numbers of mannoses and other mannosylated derivatives of lysozyme (LZM), soybean
      trypsin inhibitor (STI), superoxide dismutase (SOD) and bovine gamma
      immunoglobulin (IgG) were synthesized. Rabbit MBL was isolated by affinity column
      chromatography and immobilized on the SPR sensor chip via avidin-biotin binding.
      Binding of Man-BSAs to immobilized rabbit MBL increased with an increase in the
      number of mannose residues, primarily due to the reduction in dissociation rate.
      On the other hand, the association rate constant was similar for five
      mannosylated proteins investigated, whereas the dissociation rate constant
      differed markedly in spite of the same degree of mannosylation. Specific binding
      of mannosylated proteins to MBL may depend on the number of mannose residues and
      their steric configurations.

PMID- 16600537
TI  - Effect of soluble filler on drug release from stearic acid based compacts.
AB  - Fatty acids are potentially suitable carriers for use in the design of drug
      delivery systems, being biocompatible, biodegradable, of low toxicity
      inexpensive, with drug release being approximately proportional to the square
      root of time. However, at low drug loadings, below the critical percolation
      threshold, release is likely to be extremely slow and incomplete. To overcome
      these problems, we have investigated the use of increasing amounts of the soluble
      filler lactose on drug release. Benzoic acid and insulin were used as model low
      and high molecular weight drugs, respectively. At a 10% loading, benzoic acid was
      an order of magnitude higher than that observed for insulin. Using lactose as
      soluble filler, it was possible to effect greater release with increasing lactose
      content in the range 10-50%. Values of F, the formation factor, increased, but
      not to the same extent as for increased drug loading. The Higuchi release rate
      constant, k, was similar at lactose loadings of 5-20%, but increased rapidly at
      higher lactose loadings. Quantitatively, the addition of lactose yielded release
      rate constants 1.2-3.6 times greater than the value for lactose-free compacts in
      the case of benzoic acid and two- to five-fold in the case of insulin. A linear
      relationship was demonstrated between k, and the percentage soluble fraction of
      the matrix above the percolation threshold.

PMID- 16600538
TI  - Evaluation of ciprofloxacin-loaded Eudragit RS100 or RL100/PLGA nanoparticles.
AB  - The objective of present study was to prepare positively charged ciprofloxacin
      loaded nanoparticles providing a controlled release formulation. The particles
      were prepared by water-in-oil-in-water (w/o/w) emulsification and solvent
      evaporation, followed by high-pressure homogenisation. Two non-biodegradable
      positively charged polymers, Eudragit RS100 and RL100, and the biodegradable
      polymer poly(lactic-co-glycolic acid) or PLGA were used alone or in combination,
      with varying ratios. The formulations were evaluated in terms of particle size
      and zeta potential. Differential scanning calorimetry measurements were carried
      out on the nanoparticles and on the pure polymers Eudragit and PLGA. Drug loading
      and release properties of the nanoparticles were examined. The antimicrobial
      activity against Pseudomonas aeruginosa and Staphylococcus aureus was determined.
      During solvent evaporation, the size and zeta potential of the nanoparticles did
      not change significantly. The mean diameter was dependent on the presence of
      Eudragit and on the viscosity of the organic phase. The zeta potential of all
      Eudragit containing nanoparticles was positive in ultrapure water (around +21/+25
      mV). No burst effect but a prolonged drug release was observed from all
      formulations. The particles' activity against P. aeruginosa and S. aureus was
      comparable with an equally concentrated ciprofloxacin solution.

PMID- 16600539
TI  - In vitro transdermal delivery of caffeine, theobromine, theophylline and catechin
      from extract of Guarana, Paullinia Cupana.
AB  - Extracts of guarana (Paullinia cupana) feature as putatively stimulating
      ingredients in a number of foods, drinks and dietary/herbal supplements. The
      objective of this work was to investigate in vitro the transdermal delivery of
      the major pharmacologically active compounds contained in guarana extract.
      Saturated solutions of guarana were prepared in polyethylene glycol 400 (PEG400),
      propylene glycol (PG) and H(2)O at 32 degrees C. Guarana extract was also
      formulated in Duro-tak 2287 transdermal adhesive in a range of concentrations and
      the diffusional release was determined in addition to adhesive properties.
      Transdermal delivery across full thickness pig ear skin was investigated in vitro
      using Franz-type diffusion cells, with reverse-phase HPLC being used for the
      quantification of the permeation of theobromine (TB), theophylline (TP), (+)
      catechin (C) and caffeine (CF). Based upon a combination of release and adhesive
      property data a patch containing 5.55 mg guarana extract cm(-2) was deemed
      optimal. The general trend for the delivery of the 4 analytes was: water >5.55 mg
      cm(-2) patch approximately PG>PEG400. For CF the greatest steady state flux was
      obtained from the water vehicle: 19 microg cm(-2)h(-1), with approximately 420
      microg cm(-2) permeating after 24h. This was some 6x times more than from the
      drug-in-adhesive patch and 10x greater than PG, a well-known penetration
      enhancer, and 50x that of the 'regular' excipient PEG400. A water vehicle also
      provided the greatest delivery of TB (0.45 microg cm(-2) h(-1)), TP (0.022 microg
      cm(-2) h(-1)), and C (0.10 microg cm(-2) h(-1)). An inverse relationship was
      noted between lipophilicity and k(p) in each vehicle. The simultaneous
      transdermal delivery of the major actives of guarana was established, with
      permeation rates being highly concentration and vehicle dependent.

PMID- 16600540
TI  - Microemulsion-based hydrogel formulation of ibuprofen for topical delivery.
AB  - The purpose of this study was to construct microemulsion-base hydrogel
      formulation for topical delivery of ibuprofen. Ethyl oleate (EO) was screened as
      the oil phase of microemulsions, due to a good solubilizing capacity of the
      microemulison systems and excellent skin permeation rate of ibuprofen. The pseudo
      ternary phase diagrams for microemulsion regions were constructed using ethyl
      oleate as the oil, Tween 80 as the surfactant, propylene glycol as the
      cosurfactant. Various microemulsion formulations were prepared and the abilities
      of various microemulsions to deliver ibuprofen through the skin were evaluated in
      vitro using Franz diffusion cells fitted with porcine skins. The in vitro
      permeation data showed that microemulsions increased the permeation rate of
      ibuprofen 5.72-30.0 times over the saturated solution. The optimum formulation
      consisted of 3% ibuprofen, 6% EO, 30% Tween 80/PG (2:1) and water, showed a high
      permeation rate of 38.06 microg cm(-2) h(-1). Xanthan gum as a gel matrix was
      used to construct the microemulsion-based hydrogel for improving the viscosity of
      microemulsion for topical administration. The studied microemulsion-based
      hydrogel showed a good stability. These results indicate that the studied
      microemulsion-based hydrogel may be a promising vehicle for topical delivery of
      ibuprofen.

PMID- 16600541
TI  - Synergistic absorption enhancement of salmon calcitonin and reversible mucosal
      injury by applying a mucolytic agent and a non-ionic surfactant.
AB  - The present study investigated the intestinal absorption enhancement of salmon
      calcitonin (SCT) and the intestinal mucosal damage when a mucolytic agent and a
      non-ionic surfactant were administered simultaneously to rats. N-acetylcysteine
      (NAC) and p-t-octyl phenol polyoxyethylene-9.5 (Triton X -100, TX-100) were
      chosen as the model mucolytic agent and the non-ionic surfactant, respectively.
      Dosing solutions containing these agents were administered directly into the rat
      jejunum, and the bioavailability of SCT up to 2 h was determined. NAC and TX-100,
      when they were used alone at a dose of 1 mg/head, did not show the apparent
      enhancement compared to the control. However, simultaneous use of NAC and TX-100
      enhanced the intestinal absorption of SCT in a synergistic manner, and absolute
      bioavailability increased 12.5-fold compared to the control. The effect of NAC
      and TX-100 on SCT absorption was not dependent on their doses over the range of
      0.2-2 mg/head, and the maximum effect was obtained at a dose of 1mg/head.
      Absorption enhancement of SCT by a combination of NAC and TX-100 was compared to
      those from the classical absorption enhancers. Absorption-enhancing ability of
      the combination of NAC and TX-100 was significantly higher than those of sodium
      deoxycholate, citrate, and the combination of citrate and taurocholate, and was
      comparable with that of the combination of citrate and taurodeoxycholate.
      Finally, the intestinal mucosal damage caused by the combination of NAC and TX
      100 was assessed using a capsule device. Acute damage on intestinal mucosa was
      observed when they were exposed into rat intestine, but this morphological damage
      was found to be reversible. All these results suggest that simultaneous use of a
      mucolytic agent and a non-ionic surfactant would offer a potentiality for peroral
      delivery of peptide drugs like SCT.

PMID- 16600542
TI  - Anti-inflammatory and anti-nociceptive activities of Pluchea quitoc (DC.)
      ethanolic extract.
AB  - Pluchea quitoc DC. (Asteraceae), a plant widely distributed throughout Brazil and
      popularly known as "quitoco", "madre-cravo" or "tabacarana", is used in
      traditional medicine for the treatment of inflammation, as well as of digestive
      and respiratory diseases. The anti-inflammatory and anti-nociceptive activities
      of the ethanolic extract (EE) from aerial parts of this plant were evaluated in
      mice and rats. Oral treatment with the EE (1-2g/kg, p.o.) decreased the paw
      oedema induced by carrageenan in rats, showed anti-nociceptive effects on the
      tail-flick test and on acid-induced writhing in mice, and inhibited both phases
      of pain (neurogenic and inflammatory) of the formalin test in rats. Topical
      application (EE 1.25, 2.5 and 5.0mg) inhibited the ear oedema induced by croton
      oil in mice. The results support the folkloric use of the plant in inflammatory
      processes.

PMID- 16600543
TI  - Antimicrobial, wound healing and antioxidant activity of Plagiochasma
      appendiculatum Lehm. et Lind.
AB  - Plagiochasma appendiculatum (Aytoniaceae) of the order Marchantiales is widely
      used in the form of paste ethnomedicinally by Gaddi tribe in Kangra valley for
      treating skin diseases. In this context, antimicrobical potential of Plagiochasma
      appendiculatum against a wide range of microorganisms was studied. To validate
      the ethnotherapeutic claims of the plant in skin diseases, wound healing activity
      was studied, besides antioxidant activity to understand the mechanism of wound
      healing activity. The plant (alchoholic and aqueous extract) showed significant
      antibacterial and antifungal activity against almost all the organisms:
      Micrococcus luteus, Bacillus subtilis, Bacillus cereus, Staphylococcus aureus,
      Streptococcus pneumoniae, Enterobacter aerogenes, Escherichia coli, Klebsiella
      pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhimurium,
      and eight fungi Candida albicans and Cryptococcus albidus-dimorphic fungi,
      Trichophyton rubrum-dermatophyte fungi, Aspergillus niger, Aspergillus flavus,
      Aspergillus spinulosus, Aspergillus terreus and Aspergillus nidulans-systemic
      fungi, with especially good activity against the dermatophyte (Trichophyton
      rubrum) and some infectious bacteria (Escherichia coli, Proteus mirabilis and
      Salmonella typhimurium) with an MIC of 2.5 microg/disc. The results show that
      Plagiochasma appendiculatum extract has potent wound healing capacity as evident
      from the wound contraction and increased tensile strength. The results also
      indicated that Plagiochasma appendiculatum extract possesses potent antioxidant
      activity by inhibiting lipid peroxidation and increase in the superoxide
      dismutase (SOD) and Catalase activity.

PMID- 16600544
TI  - Effect of Solanum lycocarpum St. Hill on various haematological parameters in
      diabetic rats.
AB  - Solanum lycocarpum St. Hill (SL) is commonly used in Brazilian folk medicine. The
      aim of the present study was to evaluate the validity of the traditional
      therapeutic indication of SL as hypoglycaemic agent. The extract reduced glycemia
      to 92.4mg/dl in alloxan induced diabetic rats (230.5mg/dl). We also investigated
      the potential of SL as antioxidant (it reduced in 27% nitrate generation in
      diabetic animals). Our results also demonstrated that SL is not ulcerogenic and
      restored haemoglobin and haematocrit to normal values in diabetic animals.

PMID- 16600545
TI  - Hepatoprotective effect of extracts from Pergularia daemia Forsk.
AB  - Pergularia daemia (Asclepiadaceae) is a perennial herb growing widely along the
      road sides of India. It has been used in folk medicine for the treatment of liver
      disorders. The aim of this work is to study the hepatoprotective effect of crude
      ethanolic and aqueous extracts from the aerial parts of Pergularia daemia. The
      aqueous and ethanolic extracts obtained from aerial parts of Pergularia daemia
      were evaluated for hepatoprotective activity in rats by inducing liver damage by
      carbon tetrachloride. The ethanolic extract at an oral dose of 200 mg/kg
      exhibited a significant (P<0.05) protective effect by lowering serum levels of
      glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline
      phosphatase, total bilirubin and total cholesterol and increasing the levels of
      total protein and albumin levels as compared to silymarin used as a positive
      control. These biochemical observations were supplemented by histopathological
      examination of liver sections. The activity may be a result of the presence of
      flavonoid compounds. Furthermore, the acute toxicity of the extracts showed no
      signs of toxicity up to a dose level of 2000 mg/kg. Thus it could be concluded
      that ethanolic extract of Pergularia daemia possesses significant
      hepatoprotective properties.

PMID- 16600546
TI  - Purification of antibacterial agents from Tragia involucrata--a popular tribal
      medicine for wound healing.
AB  - Tragia involucrata has been widely used in traditional systems of medicine for a
      variety of diseases. In the present study, in vitro antibacterial properties of
      nine different compounds including vinyl hexylether, shellsol, 2,4-dimethyl
      hexane, 2-methylnonane and 2,6-dimethyl heptane were isolated from the leaf of
      Tragia involucrata studied against Escherichia coli, Proteus vulgaris and
      Staphylococcus aureus using the disc-diffusion method at 50 microg/ml
      concentrations. The compound vinyl hexylether showed a broad spectrum of
      activity. The highest activity was found in shellsol (50 microg/ml) against
      Proteusvulgaris and Staphylococcus aureus. Minimum inhibitory concentrations were
      determined for the effective compounds (MICs 2.5-40 microg/ml), shellsol and
      vinyl hexylether showed inhibitory action at the lowest dilution (10 microg/ml)
      than 2-methylnanone. Shellsol inhibited the growth of Staphylococcus aureus very
      effectively than the other compounds. These compounds showed bactericidal effects
      against all the tested bacteria (MBC, 12.25 microg/ml). However, the compound
      shellsol showed effective killing of wound causing bacteria (Staphylococcus
      aureus). So, the study was focused on the constituent to evaluate wound healing
      in rat model. Rats that received 50 microg/kg, b.w. of shellsol showed complete
      healing after 24 days. Histological examination revealed an increase in the
      fibroblast, neovascularization, granulation and thickness of scar tissue after
      the treatment of shellsol as compared to control. The topical application of
      shellsol did not cause any toxic response on rat skin. Thus, the antibacterial
      properties of the constituents give some scientific basis to its usage in
      traditional medicine.

PMID- 16600547
TI  - Anti-inflammatory and antinociceptive potential of Maclura pomifera (Rafin.)
      Schneider fruit extracts and its major isoflavonoids, scandenone and auriculasin.
AB  - The aqueous, ethanolic and chloroform extracts and two prenylated isoflavones:
      scandenone (I) and auriculasin (II), isolated from the fruits of Maclura pomifera
      (Rafin.) Schneider, were investigated for their in vivo anti-inflammatory and
      antinociceptive activity. For the anti-inflammatory activity, both carrageenan
      induced hind paw edema and 12-O-tetradecanoyl-13-acetate (TPA)-induced mouse ear
      edema models and for the antinociceptive activity, p-benzoquinone-induced
      abdominal constriction test were used. Scandenone, the chloroform and the
      ethanolic extracts were shown to possess antinociceptive activity and anti
      inflammatory activity on carrageenan-induced hind paw edema model at 100 mg/kg
      dose. The same compound and the extract were also found to be highly active in
      (TPA)-induced mouse ear edema model whereas auriculasin and the H(2)O extract
      showed to be inactive in all of the assays.

PMID- 16600548
TI  - Swiss DVI at the tsunami disaster: expect the unexpected.
AB  - The conclusions reached while considering various aspects of the implemented
      strategy in the identification procedures in the wake of the tsunami disaster of
      December 26, 2004 are outlined. The lessons to be learned are discussed.

PMID- 16600549
TI  - Problem-based analysis of bitemark misidentifications: the role of DNA.
AB  - The dental literature concerning bitemark methodology is surprisingly thin and
      sorely lacking in rigorous scientific testing. Contra to this fact, the bitemark
      legal caselaw is surprisingly strong and is used as a substitute for reliability
      testing of bite mark identification. In short, the Judiciary and the Prosecutors
      have loved forensic odontologists. This paper will focus on the author's
      participation as a Defense expert over the last seven years in over 50 bitemark
      prosecutions and judicial appeals. This sampling will act as an anecdotal survey
      of actual bitemark evidence. Certain trends regarding methods and reliability
      issues of odontologists will be discussed. Several of these cases have been later
      judicially overturned due to DNA analyses after the defendants were originally
      convicted. These diagnostic misadventures are being vocally discussed in the US
      media by news and legal investigators who are asking hard questions. The forensic
      dentistry community, however, is curiously silent. What actions are necessary by
      the profession to improve this assault on the 52-year tradition of bite mark
      identifications in the United States?

PMID- 16600550
TI  - Ossifying fibromyxoid tumor of the nasal septum.
AB  - The fibromyxoid tumor is quite a rare soft tissue tumor and typically presents as
      an ossifying fibromyxoid tumor (OFMT) in the subcutis of the extremities of
      adults. Most authors favour schwannian or chondroid origin of this lesion with
      somehow uncertain biologic dignity. Local recurrence is seen in 27% of patients
      after primary excision. We present a case of a fibromyxoid tumor of the nasal
      septum in a 49-year-old female who complained of nasal airway obstruction and
      enlargement of the right contour of the nose. Endonasal, endoscopic tumor
      excision was performed. The tumor contained spindle-shaped and polygonal cells,
      mucoid pseudocysts and a fibromyxoid stroma with local calcifications. The
      clinical behaviour of OFMT in general is benign but some reports have documented
      atypical tumors with histologic signs of malignancy. Complete local resection is
      the treatment of choice. Because of the high rate of local recurrence, clinical
      follow-up examinations are necessary.

PMID- 16600551
TI  - [Using antibiotics in case of influenza].
AB  - Acute respiratory bacterial infection is the most common complication of
      influenza and a leading cause for excess rate of outpatient visits,
      hospitalization, and death (pneumonia). Influenza promotes bacterial infection as
      stated by epidemiologic evidence of temporal association between outbreaks or
      peaks of both influenza and bacterial pneumonia. The bacteria involved are
      Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus. However,
      Gram-negative rods, Klebsiella pneumoniae, Pseudomonas aeruginosa, anaerobes and
      methicillin resistant S. aureus may be involved in institutionalized elderly
      patients. Various studies confirm that antibiotics are over-prescribed in
      patients with influenza or influenza like illness, even in the absence of
      bacterial infection signs, and in patients without comorbidity. No data has
      proven the benefice of antibiotic prescription in influenza-infected patients
      without bacterial infection. Neuraminidase inhibitors may be of interest for the
      management of influenza infected patients, because they can decrease the risk of
      bacterial complications and the use of antibiotics.

PMID- 16600552
TI  - [Prevalence of community-acquired methicillin-resistant Staphylococcus aureus].
AB  - OBJECTIVE: The authors had for aim to assess the prevalence of community-acquired
      methicillin-resistant Staphylococcus aureus in France. METHOD: Two hundred fifty
      four strains identified in 1,079 nasal samples from voluntary individuals were
      analyzed in 2002. An antibiogram (especially measuring the inhibition diameter of
      cefoxitine) and screening by oxacillin (6 mug/ml) allowed the identification of
      strains resistant to betalactams. The resistant phenotype was confirmed by
      amplification of the mecA gene by PCR. The distribution of strains was compared
      to the resistance to various antibiotics and especially to cotrimoxazole,
      macrolides, aminosides, and the mechanisms of resistance were determined.
      RESULTS: Eleven methicillin-resistant strains were detected in 254 carriers
      (4.33%), or 1% of the total population studied. CONCLUSION: Complementary tests
      (detection of the Panton-Valentine toxin, pulsed field electrophoresis) will be
      necessary to finish strain characterization. It can already be stated that
      compared to previous studies, community-acquired MRSA carriage is weak in France.

PMID- 16600553
TI  - [Influenza and travelling].
AB  - There is a risk for the traveler to acquire an exotic disease when traveling and
      to introduce it in non-endemic areas after returning. Influenza is a good example
      of such a disease. The incidence of flu in travelers is unknown. However,
      numerous outbreaks of flu have been reported in groups of travelers: package
      tours, pilgrims, elderly people, and travel by plane or cruise ships. Nowadays
      vaccination against flu is not recommended in travelers unless they belong to
      groups at risk for flu. Nonetheless vaccination against flu is difficult to apply
      to travelers due to problems in vaccine availability and inadequacy between
      vaccine strains and strains responsible for ongoing outbreaks in the opposite
      hemisphere. This vaccination seems important to travelers because flu may impair
      their vacation. In addition, it is also interesting for the community if it
      limits the spread of flu worldwide.

PMID- 16600554
TI  - [Adverse effects of intralesional Glucantime in the treatment of cutaneous
      leishmaniosis].
AB  - OBJECTIVE: The treatment of cutaneous leishmaniasis used in Tunisia is
      Glucantime. The aim of this retrospective study was to determine the adverse
      effects of intralesional Glucantime and to calculate the risk/benefit rate of
      this treatment. RESULTS: Adverse effects were observed in 14 cases (5%). For
      facial lesions, we observed facial staphylococci in 2 cases, stibio-intolerance
      in 1 case, and a palpebral subcutaneous nodule in 1 case. In limb lesions the
      complications were: sporotrichoid nodules in 5 cases, vagal malaise (1 case),
      pyodermitis (1 case), erysipelas (1 case), necrosis (1 case), and urticaria (1
      case). COMMENTARY: The adverse effects of intralesional Glucantime are mostly
      infections, mainly observed in cephalic localization, and stibio-intolerance. For
      this reason, intralesional injection of Glucantime must be avoided in the
      cephalic region.

PMID- 16600555
TI  - Senescent fibroblasts induce moderate stress in lung epithelial cells in vitro.
AB  - Epithelial-mesenchymal interactions contribute to functionality and integrity of
      the lung epithelium, which might change during ageing and associated cellular
      ageing. Therefore, we studied the effect of senescent versus pre-senescent lung
      fibroblasts (WI-38) on mitogenic and stress-protective factors in lung epithelial
      cells (H358). By use of conditioned medium, we found a growth promoting impact of
      fibroblasts compared with control medium from epithelial cells associated with
      activation of ERK1/2, Akt, p70S6K, and EGF receptor. Although senescent
      fibroblasts mediated similar growth stimulation compared with pre-senescent
      cells, we observed less protection against spontaneous mitochondrial dysfunction
      in vitro, higher production of reactive oxygen species and activation of
      copper/zinc superoxide dismutase. Moreover, senescent cells induced activation of
      caspase-3/7 in epithelial cells, which was associated with down-regulation of the
      caspase-inhibitory protein XIAP. In summary, senescent lung fibroblasts induce
      moderate stress in lung epithelial cells in vitro without affecting growth
      signaling.

PMID- 16600556
TI  - Ageing introduces a complex pattern of changes in several rat brain transcription
      factors depending on gender and anatomical localization.
AB  - As ageing changes the activity of several transcription factors in the rat
      cortex, we were interested in determining whether similar changes also appear in
      the hippocampus of old rats. We determined by electrophoretic gel shift assays
      the binding activity of nuclear factor kappa B (NFkappaB), activator protein-1
      (AP-1), peroxisome proliferator-activated receptor (PPAR), and liver X receptor
      (LXR) in cortex and hippocampus samples from young (3-month-old), and old (18
      month-old) male and female Sprague-Dawley rats. NFkappaB activity increased in
      old male and female rats, though only in cortex samples, while AP-1 activity
      decreased only in the cortex and hippocampus of old female animals. LXR activity
      decreased in all conditions, except in old male cortexes; whereas PPAR activity
      only decreased in the hippocampus of old female rats. Decreases in AP-1 and PPAR
      activities restricted to old female rats did not result from an age-related
      decline in plasma 17beta-estradiol concentration, as their activities did not
      change in samples obtained from ovariectomized young female rats. Our results
      indicate that ageing induces a complex pattern of changes in the brain-binding
      activity of NFkappaB, AP-1, PPAR and LXR, depending on the anatomical origin of
      the samples (cortex or hippocampus), and the sex of the animals studied.

PMID- 16600557
TI  - Chiral separation of cefadroxil by capillary electrochromatography.
AB  - In this paper, the chiral separation of cefadroxil was studied by capillary
      electrochromatography. Monolithic capillary column was prepared for the
      separation of cefadroxil enantiomers. The optimum buffer contained 28.5 mmol/L
      sodium acetate, 0.95% (v/v) acetic acid, 19 mmol/L beta-cyclodextrin (beta-CD)
      and 5% (v/v) isopropanol in formamide solution (pH 7.0), with the running voltage
      of 12 kV, the UV detector wavelength of 254 nm, the sample injected time of 8s
      and the temperature of 25 degrees C. Under these conditions, the column
      efficiency of cefadroxil enantiomers were N1=5324 and N2=23,768 with a
      selectivity factor (alpha) of 1.056 and resolution (Rs) of 0.978. The effect of
      buffer pH value, beta-CD concentration, organic modifier (isopropanol)
      concentration and voltage was also investigated for the separation by CEC.

PMID- 16600559
TI  - The Finch factor.

PMID- 16600558
TI  - Capillary electrophoretic determination of glucosamine in osteoarthritis tablets
      via microwave-accelerated dansylation.
AB  - A robust capillary electrophoretic method has been established to separate
      aminosaccharides including glucosamine, galactosamine, N-methyl-glucamine, N
      acetyl-glucosamine and amino glucuronic acid. All the aminosaccharides were
      dansylated fast under microwave irradiation at 385 W for 6 min (about 50-fold
      faster than common methods) and detected via on-line UV adsorption at 214 nm.
      Baseline separation of the dansylatied products was achieved in 20 min using a
      running buffer of 320 mM borate at pH 9.50. Quantitation of glucosamine in
      osteoarthritis tablets was then conducted. A linear working range was found in
      between 2.00 microg/mL and 1.80 mg/mL with linear regression coefficient of
      0.9964. The limit of detection reached 1.00 microg/mL glucosamine (signal-to
      noise, S/N=3). Recoveries were determined by spiking a known amount of
      glucosamine in tablet-extracted solutions, giving a range of 88.0-99.7%. The run
      to-run relative standard deviation was 0.24% (n=5) for migration time and 2.72%
      for peak area.

PMID- 16600560
TI  - Harm and benefits of short-term pre-operative radiotherapy in patients with
      resectable rectal carcinomas.
AB  - AIM: To weigh the harms and benefits of short-term pre-operative radiotherapy in
      the treatment of resectable rectal cancer. METHODS: The benefits (reduction of
      local recurrence) and harm (increase of short-term complications) of short-term
      pre-operative radiotherapy are balanced using a model which classifies patients
      in one of five outcome combinations; 1-benefit without additional harm, 2-benefit
      with additional harm, 3-no benefit, no additional harm, 4-no benefit but
      additional harm, 5-mortality due to combined treatment. The results of four
      randomised clinical trials (RCT) which study the addition of short-term pre
      operative radiotherapy in rectal cancer were classified according to this model.
      RESULTS: Five to thirteen percent of the patients have benefit without additional
      harm of pre-operative radiotherapy, while 0-2% have benefit with additional harm;
      74-87% has neither benefit nor additional harm and 6-11% have no benefit but
      additional harm. A small percentage of patients (1-6%) dies post-operatively as a
      result of the addition of radiotherapy. CONCLUSION: This model provides a
      transparent appreciation of the harmful and beneficial effects of any treatment
      modality investigated by means of a randomised clinical trial. As for short-term
      pre-operative radiotherapy in resectable rectal cancer is shown, a small
      percentage of patients benefits from such treatment. Most patients have neither
      benefit nor additional harm, while a small percentage suffers from additional
      harm while not receiving any benefit.

PMID- 16600561
TI  - [Streptococcal pneumonia with toxic shock syndrome].

PMID- 16600562
TI  - [Implementation of the French law related to the patients' rights and the end of
      life].

PMID- 16600563
TI  - [Right main bronchus tumoral obstruction during left pneumonectomy].
AB  - We report a case of severe airway obstruction during a pneumonectomy, due to a
      tumor embolus in the contralateral main bronchus. Trachea was intubated with a
      single-lumen tube with a bronchial blocker. This kind of accident is very rare,
      and often fatal. The mass was retrieved by rigid bronchoscopy and the patient
      made an uneventful recovery.

PMID- 16600564
TI  - [Aphasia and facial paralysis after peribulbar anesthesia].

PMID- 16600565
TI  - [Hepatic infarction and protein C deficiency].

PMID- 16600566
TI  - Oxovanadates: a novel probe for studying lipid-water interfaces.
AB  - How water, metabolites and proteins associate and traverse the lipid interface is
      generally investigated by using probes with spectroscopic handles. Cellular
      confinement limits the tools of investigation to indirect approaches. Studies of
      a variety of different probes become important to understand the effects of
      confinement on chemical reactions and biological function. Confinement of water
      affects the properties of water and this effect is important for cellular
      systems. A versatile model system for studying the effect of water confinement on
      biological processes uses reverse micelles (RMs). Molecular probes are also used
      to investigate environments that are not readily accessible to direct
      measurements. Most of the dyes in use contain large hydrophobic chromophores and
      do not have size and structural flexibility to probe a surface that is both
      hydrophobic and hydrophilic as common in biological systems. We present the use
      of vanadium-containing probes for exploration of the fundamental properties of
      restricted water and lipid interfaces in RMs. The presence of a vanadium atom in
      these probes provides multiple handles such as chemical shifts, signal linewidth
      and lifetime experiments in the quadrupolar 51V nuclei as well in 1H and 13C
      nuclei for investigations. The quadrupolar nuclei have a greater battery of
      useful spectroscopic parameters and combined with the conventional methods
      provide multiple handles in one probe. Furthermore, the vanadium-containing probe
      structure, charge and polarity can be modified for use in various biological
      settings. Here we introduce the concept and describe a few applications of this
      approach.

PMID- 16600567
TI  - Effects of sodium arsenite on catalase activity, gene and protein expression in
      HaCaT cells.
AB  - The objective of this research work is to study the effects of sodium arsenite on
      activity, mRNA and protein expression of catalase (CAT) in established human cell
      lines of keratinocytes (HaCaT). Based on the AlamarBlue assay, we found that a
      high level (100 micromol/l) of sodium arsenite inhibited cell viability. The
      reactive oxygen species (ROS) content in cells was increased in all treated
      cultures dose-dependently. CAT activity, mRNA expression and protein levels were
      decreased by 5-20 micromol/l of sodium arsenite. It is highly suggestive that CAT
      gene expression and protein levels are affected by arsenic.

PMID- 16600568
TI  - Promoter motifs of olfactory receptor genes expressed in distinct topographic
      patterns.
AB  - Novel olfactory receptor-encoding genes that are expressed in olfactory sensory
      neurons arranged in a clustered pattern in the nasal epithelium, typical of the
      mOR262 (approved gene symbol Olfr) family, were identified. The genes share
      sequence motifs upstream of their transcription start sites that are highly
      related to those previously identified as characteristic of the mOR262 genes,
      suggesting that these regulatory elements may contribute to governing their
      unique expression pattern. Promoter analyses of genes encoding class I receptors
      that are expressed in the dorsal region of the epithelium revealed a different,
      but again common set of sequence motifs. A prominent feature of the class I gene
      promoters are multiple O/E-like binding sites, and O/E-type transcription factors
      that bind to the putative promoter region of class I OR genes were in fact
      identified. The findings support the concept that common elements in the promoter
      region of these OR genes may determine their congenic expression pattern in the
      epithelium.

PMID- 16600569
TI  - Special issue on the brain mechanisms of imitation learning.

PMID- 16600570
TI  - The N-terminus of PKR is responsible for the activation of the NF-kappaB
      signaling pathway by interacting with the IKK complex.
AB  - The interferon-induced double-stranded RNA (dsRNA)-activated protein kinase (PKR)
      has been shown to activate NF-kappaB independently of its kinase function after
      interaction with the IKK complex. In order to investigate the mechanism of NF
      kappaB activation by PKR, we identified the domain of PKR responsible for
      stimulating the NF-kappaB pathway in PKR-deficient fibroblasts using an NF-kappaB
      dependent reporter assay. The N-terminal 1-265 AA of PKR activates NF-kappaB,
      whereas the 1-180 AA N-terminus restricted to the two dsRNA Binding Domains
      (DRBD), the third basic domain alone (AA 181-265), or the C-terminus of PKR (AA
      266-550) were unable to stimulate the expression of the NF-kappaB dependent
      reporter gene. Using confocal microscopy, we confirmed that PKR full length as
      well as PKR N-terminus colocalized with IKKbeta. By GST-pulldown analysis, using
      different PKR domains, we then revealed the specific ability of the PKR N
      terminus 1-265 to bind to and activate IKK and showed that this activation
      requires the integrity of the IKK complex. This activation is not only due to
      DRBDs since the DRBD fragment 1-180 failed to inhibit PKR 1-265 induced NF-kappaB
      activation. Our results therefore demonstrate that the ability of PKR to mediate
      NF-kappaB activation resides in its full N-terminus, and requires both DRBDs and
      the third basic domain.

PMID- 16600571
TI  - Human cathelicidin LL-37 increases vascular permeability in the skin via mast
      cell activation, and phosphorylates MAP kinases p38 and ERK in mast cells.

PMID- 16600572
TI  - The levels of serum neopterin in Behcet's disease--objective marker of disease
      activity.

PMID- 16600573
TI  - Induction of versican by ascorbic acid 2-phosphate in dermal papilla cells.

PMID- 16600574
TI  - Posttraumatic stress disorder in victims of the March 11 attacks in Madrid
      admitted to a hospital emergency room: 6-month follow-up.
AB  - PURPOSE: To determine the change in prevalence of posttraumatic stress disorder
      (PTSD) symptoms in victims of the March 11 attacks and their relatives, 1 and 6
      months after the attacks. SUBJECTS AND METHODS: Evaluation of PTSD symptoms using
      the Davidson Trauma Scale (DTS) and General Health Questionnaire (GHQ) in a
      sample of 56 patients admitted to an emergency room of a general hospital, and
      assessment of PTSD symptoms in relatives of the patients. RESULTS: At Month 1,
      41.1% of patients (31.3% of males and 54.2% of females) presented with PTSD. At
      Month 6, this figure was 40.9% (30.4% of males and 52.4% of females). There was a
      significant improvement in perception of health among females between Month 1 and
      Month 6. Relatives presented similar DTS scores at baseline and at 6 months.
      DISCUSSION: We verified that rates of PTSD did not vary substantively between the
      two evaluations. PTSD symptoms positively correlated with psychological health
      involvement. This correlation points out that both PTSD symptoms and subjective
      general health involvement are part of the psychological response to trauma.
      CONCLUSION: The prevalence of PTSD symptoms was high and remained stable between
      Month 1 and Month 6, while subjective perception of health improved
      significantly.

PMID- 16600575
TI  - Isobolographic analysis of interactions between losigamone and conventional
      antiepileptic drugs in the mouse maximal electroshock model.
AB  - The aim of this study was the isobolographic evaluation of interactions between
      losigamone (LSG), valproate (VPA), carbamazepine (CBZ), phenytoin (PHT), and
      phenobarbital (PB) in the maximal electroshock (MES) test in mice.
      Electroconvulsions were produced by means of an alternating current (ear-clip
      electrodes, 0.2-s stimulus duration, and tonic hindlimb extension taken as the
      endpoint). Adverse effects were evaluated in the chimney test (motor
      coordination) and the passive avoidance task (long-term memory). Brain
      concentrations of antiepileptic drugs (AEDs) were measured by immunofluorescence
      or high-performance liquid chromatography. Isobolographic analysis indicated
      synergistic interactions between LSG and VPA. For example, in the proportion of
      1:1 the theoretically calculated 50% effective dose for additivity (ED(50add))
      was 138 mg/kg, while the experimentally derived ED(50) for the mixture
      (ED(50mix)) was 85.2 mg/kg. The difference was significant at p<0.001. LSG
      combined with CBZ or PHT showed additivity, whereas the combinations of LSG with
      PB were either additive, for the fixed ratios of 1:3 and 1:1, or antagonistic for
      the ratio of 3:1 (ED(50add)=18.4 mg/kg versus ED(50mix)=26.7 mg/kg, p<0.05).
      Impairment of long-term memory was noted only in the case of VPA given at its
      ED(50), however this AED did not affect motor performance. LSG, CBZ, PHT and PB
      (applied at their ED(50) values) and co-administration of LSG with conventional
      AEDs (including VPA) impaired neither motor performance nor long-term memory. LSG
      did not affect the brain concentration of VPA or PB, but significantly elevated
      the brain concentrations of CBZ and PHT. In contrast, VPA, CBZ and PHT
      significantly increased the brain concentration of LSG, indicating a
      pharmacokinetic contribution to the observed pharmacodynamic interactions.
      Although LSG exhibited some favorable pharmacodynamic interactions with various
      AEDs, these were complicated by pharmacokinetic interactions and emphasize the
      importance of measuring AED concentrations in studies designed to identify
      desirable AED combinations.

PMID- 16600576
TI  - Effect of water deficits on the activity of anti-oxidative enzymes and
      osmoregulation among three different genotypes of Radix Astragali at seeding
      stage.
AB  - Water is a key factor influencing the yield and quality of crops. Plants mainly
      adapt to water deficits by biochemical changes and osmotic adjustment (OA).
      Research on drought tolerance of field crops has been done intensively, but there
      is little work to be done in medical plants. Traditional Chinese medicine (TCM)
      has a long history of several thousand years. TCM is playing an important role in
      daily life in China and applied widely in clinical experience on the globe. More
      and more wild medical plants are cultivated and introduced. It is known that
      ecological and environmental conditions are vital to cultivation and efficient
      component accumulation of medical plants. This study is concerned about
      biochemical changes of three genotypes of Radix Astragali during water deficient
      periods and we evaluated the relative ability of their drought tolerance on the
      above basis. We analyzed the effect of soil water deficits on antioxidant enzymes
      activity and osmoregulation substances in R. Astragali leaves of three genotypes
      collected on day 0, 5, 10, 15, 20 and 25 after onset of water deprivation. Under
      water deficient conditions, biochemical changes include protecting enzyme system,
      for instance superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD).
      Osmoregulation matters include proline (Pro) and soluble sugar. Antioxidant
      enzyme activities and Pro, and soluble sugar content correlated between water
      deficient degree and time course. Antioxidant enzyme activities increased before
      20 days, then decreased at the end of experiment. Proline content increased
      gradually, and soluble sugar content reached the highest on day 20. The order of
      the ability of drought tolerance in three genotypes of R. Astragali is
      Mongolia>Wild>Hebei by using index of drought tolerance. The research results are
      instructive for cultivation and introduction of R. Astragali under different
      conditions of water status.

PMID- 16600577
TI  - Human fibrinogen adsorption onto single-walled carbon nanotube films.
AB  - The adsorption behavior of human fibrinogen (Hfg) on single-walled carbon
      nanotube (SWNT) films was investigated using scanning electron microscopy (SEM)
      and near edge X-ray absorption fine structure (NEXAFS) spectroscopy. It was shown
      in the SEM images that fibrinogen was adsorbed strongly on the surface of SWNT
      when the samples were incubated in the Hfg solutions for 10 min. The dependence
      of adsorption on the concentration of fibrinogen was also investigated and it was
      found that adsorption increased with increasing concentration. In order to
      further explore the adsorption of fibrinogen on SWNT surface, NEXAFS spectra were
      obtained at the N K-edge and the C K-edge. The results confirmed the conclusion
      regarding the dependence of adsorption on fibrinogen concentration. It is
      demonstrated that, due to its high sensitivity to the surface elements, NEXAFS
      spectroscopy is a powerful tool to investigate the adsorption of fibrinogen on
      SWNT films.

PMID- 16600578
TI  - [Necrotizing pneumonia and arthritis due to Staphylococcus aureus producing
      Panton and Valentine leukocidin in a 10-year-old boy].
AB  - Staphylococcal necrotizing pneumonia producing the Panton Valentine leukotoxin
      (PVL) has been described for many years. The french reference center for
      staphylococcal toxaemia defined it with precision in 1999. A 10-year-old child,
      died in 36 hours from respiratory distress and shock. Staphylococcal pneumonia
      was suspected then confirmed: S. Aureus producing PVL was isolated in lung, blood
      and articulations.

PMID- 16600579
TI  - Web-based adaptive training simulator system for cardiac life support.
AB  - OBJECTIVE: We introduce a web-based adaptive training simulator system to
      exercise cardiopulmonary resuscitation skills. Our purpose is to provide
      emergency physicians with an additional training tool for cardiac life support
      clinical cases, by integrating an adaptive learning environment with a web-based
      case simulator. METHODS AND MATERIALS: Adaptive systems reflect some features of
      the user in the user model and apply this model to adapt various visible aspects
      of the system to the user. Our system follows a stage-based learning model with
      several steps to personalize student learning. First, students learn the theory
      and content of life support and take computerized tests to evaluate their
      declarative knowledge of these areas. Second, they practice with clinical case
      examples and complete an exam at the appropriate level of difficulty to assess
      their practical knowledge. Finally, they train with additional clinical cases.
      RESULTS AND CONCLUSION: In order to evaluate the usefulness of the system, we
      used it in two traditional advanced life support courses at the Jaen Hospital in
      Spain, as an additional and complementary tool within the course. Results show
      that the use of adaptation techniques can improve student performance.

PMID- 16600580
TI  - Skin structure and cornification proteins in the soft-shelled turtle Trionyx
      spiniferus.
AB  - In contrast to most chelonians, the fully aquatic soft-shelled turtles have a
      smooth, unscaled, and pliable shell. The skin of the shell, tail, limbs, and neck
      of juveniles of Trionyx spiniferus has been studied by ultrastructural,
      immunocytochemical, and immunoblotting methods. The epidermis of the carapace and
      plastron has a thick corneous layer composed of alpha-corneocytes surrounded by a
      cornified cell envelope. The softer epidermis is similar to that of the shell but
      the epidermis and corneous layer are much thinner. Pre-corneous cells in both
      soft and shell epidermis are rich in vesicles produced in the Golgi apparatus and
      smooth endoplasmic vesicles, and contain numerous dense-core mucus-like and
      vesicular (lamellar) bodies. Secreted material is present among corneocytes where
      it probably forms an extensive intercellular lipid-mucus waterproof barrier. The
      dermis is very thick and composed of several layers of collagen bundles that form
      a plywood-patterned dermis. This dermis constitutes a strong mechanical barrier
      that compensates for the low content in beta-keratin, and lack of cornified
      scutes and dermal bones. The growth of the shell mainly occurs along the lateral
      margins. Immunocytochemistry reveals the presence of some beta-keratin in soft
      and shell epidermis, and this is confirmed by immunoblotting where bands at 18
      and 32-35 kDa are present. Other proteins of the cornified cell envelope
      (loricrin and sciellin) or associated to lipid trafficking (caveolin-1) are also
      detected by immunoblotting. Loricrin positive bands at 24 and 57 kDa are present
      while bands cross-reactive for sciellin are seen at 45 and 53 kDa. Caveolin-1
      positive bands are seen at 21-22 kDa. The presence of these proteins indicates
      that the epidermis is both coriaceous and waterproof. These results suggest that
      the shell of Trionyx is tough enough to be as mechanically efficient as the hard
      shell of the other turtles. At the same time, a soft shell is lighter, its shape
      is more easily controlled by muscles, and it allows a more controlled closure and
      retraction of limbs and neck inside the shell. Thus, the shell makes the animal
      more streamlined for swimming.

PMID- 16600581
TI  - Testing phylogenetic implications of eggshell characters in side-necked turtles
      (Testudines: Pleurodira).
AB  - Amniote egg and eggshell morphology is a rich source of characters to link
      aspects of reproductive biology with systematics. Extensive work concerning both
      anatomy and phylogenetic assignability has been done on fossil bird and dinosaur
      eggs, but little is known for extant sauropsids. The utility of eggshell
      characters for phylogenetic analyses is tested and discussed for extant side
      necked turtles (Pleurodira), and the diversity of egg ultrastructure is examined
      in several species. Egg gross morphology and eggshell ultrastructure of 12
      species of extant side-necked turtles was documented using scanning electron
      microscopy. Thirteen eggshell characters were scored and mapped on a composite
      phylogeny and ancestral character states were reconstructed. Many of the
      characters do not show a phylogenetic signal according to a test comparing the
      number of steps on the chosen phylogeny with that on randomly generated trees.
      The presence of conservative, clade-supporting features could be demonstrated,
      and the following clades are supported by several characters: the Elseya-Emydura
      entity, short-necked Australasian chelids, is backed by two characters, and two
      additional characters could potentially support this group. Three characters
      support the monophyly of South American chelids, whereas two characters argue for
      the exclusion of Hydromedusa, a long-necked form resembling Australian chelids
      rather than South American forms, from this clade.

PMID- 16600582
TI  - Postnatal allometry of the skeleton in Tupaia glis (Scandentia: Tupaiidae) and
      Galea musteloides (Rodentia: Caviidae)--a test of the three-segment limb
      hypothesis.
AB  - During the evolution of therian mammals, the two-segmented, sprawled tetrapod
      limbs were transformed into three-segmented limbs in parasagittal zig-zag
      configuration (three-segment limb hypothesis). As a consequence, the functional
      correspondence of limb segments has changed (now: scapula to thigh, upper arm to
      shank, fore arm plus hand to foot). Therefore, the scapula was taken into account
      in the current study of the postnatal growth of the postcranial skeleton in two
      small mammalian species (Tupaia glis, Galea musteloides). Comparisons were made
      between the functionally equivalent elements and not in the traditional way
      between serially homologous segments. This study presents a test of the three
      segment limb hypothesis which predicts a greater ontogenetic congruence in the
      functionally equivalent elements in fore and hind limbs than in the serially
      homologous elements. A growth sequence, with decreasing regression coefficients
      from proximal to distal, was observed in both species under study. This proximo
      distal growth sequence is assumed to be ancestral in the ontogeny of eutherian
      mammals. Different reproductive modes have evolved within eutherian mammals. To
      test the influence of different life histories on ontogenetic scaling during
      postnatal growth, one species with altricial juveniles (Tupaia glis) assumed to
      be the ancestral mode of development for eutherians and one species with derived,
      precocial young (Galea musteloides) were selected. The growth series covered
      postnatal development from the first successive steps with a lifted belly to the
      adult locomotory pattern; thus, functionally equivalent developmental stages were
      compared. The higher number of allometrically positive or isometrically growing
      segments in the altricial mammalian species was interpreted as a remnant of the
      fast growth period in the nest without great locomotor demands, and the clearly
      negative allometry in nearly all segments in the precocial young was interpreted
      as a response to the demand on early locomotor activity. Different life histories
      seem to have a strong influence on postnatal ontogenetic scaling; the effects of
      the developmental differences are still observable when comparing adults of the
      two species.

PMID- 16600583
TI  - Niacin skin-flush response and electrodermal activity in patients with
      schizophrenia and healthy controls.
AB  - Patients with schizophrenia have in different studies shown reduced niacin
      sensitivity and lower electrodermal activity (EDA) after auditory stimulation.
      Peripheral mediation of prostaglandins may have a physiological role in both
      responses. This motivates study of both niacin response and electrodermal
      responding in the same patients with schizophrenia. Thirty patients with
      schizophrenia and 17 controls were investigated with EDA and thereafter given
      200mg niacin orally with continuous assessment of skin temperature. The patients
      showed a delayed temperature increase after niacin ingestion (P=0.002) and a
      higher frequency of electrodermal non-responding (P<0.05). Response/non-response
      for niacin correlated with EDA response/non-response in the patient group
      (P=0.009). The niacin test revealed a slower vasodilation reaction in the
      patients. The association between response patterns for the niacin test and EDA
      suggests that a common aberration in skin physiology may be of importance for
      both reactions in schizophrenia.

PMID- 16600584
TI  - Mineralogical characterization of the Tournemire argillite after in situ
      interaction with concretes.
AB  - This study aims to investigate, through mineralogical characterization (SEM, XRD)
      and mass-balance calculations, the effects of contact time, concrete types and
      presence of free water on the Tournemire argillite under in situ conditions.
      Three sampling zones from Excavation Disturbed Zone (EDZ) areas have been chosen:
      (1) dry contacts, collected at the tunnel masonry/argillite interface (contact
      time - 125 years), (2) wet contacts, taken close to drained areas below the
      tunnel roadbed in contact with the canal draining the Cernon fault water (contact
      time - 15 and 7 years) and at the tunnel masonry/argillite interface over 70 m
      from the Cernon fault (contact time - 125 years). This study shows that: in the
      absence of water, no significant modification of argillite is observed after 125
      years, except for pyrite dissolution and gypsum precipitation; in the presence of
      water, precipitation of gypsum, recrystallization of mixed-layer clays,
      neoformation of zeolites and K-feldspars overgrowths are observed. At the
      concrete/argillite interface near the Cernon fault, important dolomite
      neoformation and leaching of chlorite and kaolinite occur. These processes are
      enhanced with contact time, low flow rate and the nature of the concrete
      (compound cement Portland CEM II 32.5). Evidence for oxidation processes linked
      to the EDZ (pyrite oxidation, Fe-oxy-hydroxide and gypsum precipitation) is
      observed.

PMID- 16600585
TI  - A methodology for solid waste characterization based on diminishing marginal
      returns.
AB  - A methodology is developed for estimating the number of waste sorts for
      characterizing solid wastes into categories based on diminishing minimum
      incremental information. Convergence in the square of the coefficient of
      variation with successive waste sorts is used to indicate cost-efficient
      termination of sampling at substantially reduced numbers of sorts in comparison
      with existing methodologies. These findings indicate that the numbers of waste
      sorts beyond that determined using the proposed methodology do not add
      substantial marginal gains in information and/or reduction in the confidence
      interval of the estimate. The methodology is demonstrated using waste composition
      analyses from the Greater Vancouver Regional District where 22 waste sorts are
      examined. The proposed methodology is simple, and the number of waste sorts can
      be estimated with a hand-held calculator and utilized in the field.

PMID- 16600586
TI  - Bipolar resistivity profiling of 3D tissue culture.
AB  - We describe a new low-cost technique for continuous monitoring of the thickness
      of biofilms and tissue cultures, and we demonstrate the advantage of using
      electrodes of different dimensions to probe different depths of a sample. We have
      used electric impedance spectroscopy to monitor keratinocyte stem cells (YF29)
      growing on an array of Ti/Pt coplanar microelectrodes. The thickness of the
      sample was reconstructed by fitting the measurements to theoretical curves. We
      have developed an algorithm for the rapid calculation of the resistance through a
      multilayered sample. This algorithm is based on conformal mapping and the serial
      partial capacitance technique. The validity of the technique was tested by
      measuring the sedimentation rate of an alumina powder. Sample thicknesses between
      10 and 80 microm could be measured with a resolution of a few microns using the
      device.

PMID- 16600587
TI  - Structure and biosensor characteristics of complex between glucose oxidase and
      plasma-polymerized nanothin film.
AB  - The structure and biosensor characteristics of complex between glucose oxidase
      (GOD) and plasma-polymerized nanothin film (PPF), in which the thickness is
      several nanometers, were investigated by atomic force microscopy (AFM) and
      electrochemical measurement. The GOD molecules were densely adsorbed onto the PPF
      surface treated by nitrogen plasma and the individual GOD molecules were
      observed. Subsequently, the GOD densely packed array on the PPF surface was
      subsequently treated by plasma polymerization (overcoating). AFM image showed
      that the thicker film gave the smoother surface, indicating that the GOD adsorbed
      on the surface was embedded more deeply in PPF. The amperometric biosensor
      characteristics of the GOD-PPF complex on a platinum electrode showed the current
      increment due to the enzymatic reaction with glucose addition, indicating that
      enzyme activity was retained although the enzyme has been exposed to the plasma
      gas related to diffusion of the substrate. This means that under mild exposure to
      organic plasma, the enzyme does not become seriously dysfunctional. Amperometric
      biosensor characteristics were strongly affected by monomer and thickness of PPF
      overcoating related with the diffusion of the substrate (glucose). Considering
      that the film deposition was performed using microfabrication-compatible organic
      plasma, our new method for protein architecture has a great potential of enabling
      high throughput production of bioelectronic devices.

PMID- 16600588
TI  - Development of immunosensor based on OWLS technique for determining Aflatoxin B1
      and Ochratoxin A.
AB  - Mycotoxins are toxic secondary metabolites produced by a number of different
      fungi, and can be present in a wide range of food and feed commodities including
      cereal grains, oil seeds, dried fruits, apple juice, wine and meat products from
      animals fed contaminated meal. Many mycotoxins are highly resistant, and survive
      food processing, and therefore enter the food chain and provide a threat to human
      health. The optical waveguide lightmode spectroscopy (OWLS) technique has been
      applied to the detection of Aflatoxin and Ochratoxin in both competitive and in
      direct immunoassays. After immobilizing the antibody or antigen conjugate for the
      direct or indirect measurement, respectively, the sensor chip was used in flow
      injection analyser (FIA) system. When using non-competitive method, sensor
      responses were obtained first only at analyte concentrations of 5-10 ng ml(-1).
      In both cases, the responses were very unstable. For competitive sensor
      investigation with the sensitized chip first the optimal dilution rate of
      monoclonal antibodies was determined, for the measurement of Ochratoxin A and
      Aflatoxin B1 the monoclonal antibody stock solution was diluted to 1 microg ml(
      1) and to a 1:400 dilution, respectively. During the competitive measurement
      standard solutions were mixed with monoclonal antibodies at the appropriate
      concentration, the mixture was incubated for 1 min and injected into the OWLS
      system. The sensitive detection range of the competitive detection method was
      between 0.5 and 10 ng ml(-1) in both cases. After the establishment of the
      indirect method, barley and wheat flour samples were measured, and the results
      were in good correlation by those measured by enzyme linked immuno-sorbent assay
      (ELISA). Regression coefficient between the two methods for Ochratoxin and
      Aflatoxin was determined as 0.96 and 0.89, respectively.

PMID- 16600589
TI  - Direct electrochemistry of horseradish peroxidase based on biocompatible
      carboxymethyl chitosan-gold nanoparticle nanocomposite.
AB  - The nanocomposite composed of carboxymethyl chitosan (CMCS) and gold
      nanoparticles was successfully prepared by a novel and in situ process. It was
      characterized by transmission electron microscopy (TEM) and Fourier transform
      infrared spectrophotometer (FTIR). The nanocomposite was hydrophilic even in
      neutral solutions, stable and inherited the properties of the AuNPs and CMCS,
      which make it biocompatible for enzymes immobilization. HRP, as a model enzyme,
      was immobilized on the silica sol-gel matrix containing the nanocomposite to
      construct a novel H(2)O(2) biosensor. The direct electron transfer of HRP was
      achieved and investigated. The biosensor exhibited a fast amperometric response
      (5s), a good linear response over a wide range of concentrations from 5.0 x 10(
      6) to 1.4 x 10(-3)M, and a low detection limit of 4.01 x 10(-7)M. The apparent
      Michaelis-Menten constant (K(M)(app)) for the biosensor was 5.7 x 10(-4)M. Good
      stability and sensitivity were assessed for the biosensor.

PMID- 16600590
TI  - Survival from rectal and anal cancers in England and Wales, 1986-2001.
AB  - The aim of this study was to investigate the effects of tumour and patient
      characteristics on trends in the survival of patients with cancer of the anus or
      rectum in England and Wales. A total of 132,542 adults (15-99 years) who were
      diagnosed during the 14 years 1986-1999 were followed up to 2001 through the
      National Health Service Central Register. Relative survival up to 5 years after
      diagnosis was estimated, using deprivation-specific life tables. Generalised
      linear models were used to estimate relative excess risks of death, adjusted for
      patient and tumour characteristics. The results showed that 5-year relative
      survival was higher in women, younger patients and more affluent patients, and
      higher for anal cancer than rectal cancer. Survival improved by more than 10%
      from the late 1980s (around 38%) to the late 1990s (49%). This trend was not
      explained by changes in the distribution of age, anatomical site, morphology or
      deprivation. The trend was more marked in younger and more affluent patients, and
      for adenocarcinoma and epidermoid carcinoma than for tumours with other
      morphology. The inequality in survival between affluent and deprived patients
      widened. It is concluded that improvements in survival may reflect improvements
      in disease stage, diagnostic technique or treatment. Which of these factors
      contribute to the widening socioeconomic inequalities in survival remains to be
      elucidated.

PMID- 16600591
TI  - Activation function 1 domain plays a negative role in dimerization of estrogen
      receptor beta.
AB  - Transcriptional potential of estrogen receptor beta (ERbeta) depends on the
      ligand binding and subsequent dimerization of the receptor protein. In order to
      examine the role of N-terminally located activation function 1 (AF-1) protein
      domain in the dimerization process of ERbeta, we used yeast SOS-Recruitment
      System (SRS). Two variants of ERbeta protein were expressed in the yeast cells:
      full length receptor and a truncated form, lacking AF-1. We observed that upon
      17beta-estradiol treatment only the shorter form of the receptor dimerized,
      whereas the full-length one did not. This result suggests an inhibitory function
      of AF-1 in dimer formation and supports previous studies showing that N-terminal
      domain of ERbeta suppresses transcriptional activity.

PMID- 16600592
TI  - Reverse osmosis processing of organic model compounds and fermentation broths.
AB  - Post-treatment of an anaerobic fermentation broth was evaluated using a 150
      gal/day, single cartridge prototype reverse osmosis (RO) system. Baseline tests
      were conducted at 25 degrees C using six organic model compounds representing key
      species found in the fermentation broth: ethanol, butanol, acetic acid, oxalic
      acid, lactic acid, and butyric acid. Correlations of the rejection and recovery
      efficiencies for these organic species, individually and in simulated mixtures,
      were obtained as a function of feed pressure with and without recirculation of
      the retentate. The actual fermentation broth obtained from a continuous-flow
      biohydrogen process was treated by the RO system under the operating conditions
      similar to those used in the baseline tests, resulting in greater than 95%
      removal of total organic carbon. These results are encouraging and useful for
      further studies on the feasibility of incorporating the RO technology into an
      integrated and field deployable wastewater management and water recovery system.

PMID- 16600593
TI  - Production of multiple xylanolytic and cellulolytic enzymes by thermophilic
      fungus Myceliophthora sp. IMI 387099.
AB  - This study reports the production of xylanolytic and cellulolytic enzymes by a
      thermophilic fungal isolate Myceliophthora sp. using a cheap medium containing
      rice straw and chemically defined basal medium under solid-state culture. A
      combination of one factor at a time approach followed by response surface
      methodology using Box-Behnken design of experiments resulted in 2.5, 1.25, 1.28
      and 4.23 fold increase in xylanase, endoglucanase, beta-glucosidase and FPase
      activity, respectively. The zymograms developed against IEF gels showed that
      multiple isoforms of xylanase (5), endoglucanase (4) and beta-glucosidase (2)
      were produced under optimized culture conditions. Moreover, thiol containing
      serine proteases produced during the growth of the culture had no role in the
      post-translational modification of these xylanases.

PMID- 16600595
TI  - An exploratory theoretical elucidation on the peroxyl-radical-scavenging
      mechanism and structure-activity relationship of nonsteroidal anti-inflammatory
      drugs.
AB  - The peroxyl-radical-scavenging mechanism of some nonsteroidal anti-inflammatory
      drugs (NSAIDs), namely tolmetin, ketorolac, indomethacin, acemetacin, and
      oxaprozin, is clarified by combined density functional theory (DFT) calculations.
      It is revealed that H-atom-abstraction rather than electron transfer reaction is
      involved in the radical-scavenging process of these NSAIDs in polar aqueous
      solution. This seems contrary to the common viewpoint that the latter is
      predominant in polar media. The calculated results also show that H-atom at
      C(beta) or C(gamma) position is readily to be abstracted, and the lowest C-H bond
      dissociation enthalpy (BDE) can qualitatively account for the activity difference
      for the five NSAIDs.

PMID- 16600594
TI  - Enhanced pharmacokinetic properties of 1,4-benzodiazepine-2,5-dione antagonists
      of the HDM2-p53 protein-protein interaction through structure-based drug design.
AB  - Guided by structure-based drug design, modification of the 1,4-benzodiazepin-2,5
      dione lead compound 1 resulted in the discovery of 19, a potent and orally
      bioavailable antagonist of the HDM2-p53 protein-protein interaction (FP IC50 =
      0.7 microM, F approximately 100%).

PMID- 16600596
TI  - Breast conservation without mammography? Oncology practice in the real world of
      limited resource countries.

PMID- 16600597
TI  - Developing a care program to better know the chronically critically ill.
AB  - Patients requiring prolonged periods of intensive care and mechanical ventilation
      are termed chronically critically ill. These patients present a challenge to the
      healthcare team. In the fast-paced environment of the intensive care unit, their
      slow progress can be a source of frustration. At the University Hospital Geneva,
      a team, led by a clinical nurse specialist, addressed this problem by
      implementing a new care program with a goal to better know this patient
      population and improve their care. Values of emancipatory practice development
      guided the project, which utilized an action research methodology. Key assessment
      tools included a nursing focused patient history at admission and weekly nursing
      rounds, which allowed for periodic holistic assessment and care planning. New
      interventions focused on communication, physical care, and providing a context of
      understanding for the patient beyond hospitalisation, operationalised as a
      patient diary. The structure of the new program allowed the nurses to develop new
      skills and provided an environment for dynamic reflection. The care of this
      demanding patient population is beginning to be perceived by nurses as
      challenging and interesting.

PMID- 16600598
TI  - Folding of small disulfide-rich proteins: clarifying the puzzle.
AB  - The process by which small proteins fold to their native conformations has been
      intensively studied over the past few decades. The particular chemistry of
      disulfide-bond formation has facilitated the characterization of the oxidative
      folding of numerous small, disulfide-rich proteins with results that illustrate a
      high level of diversity in folding mechanisms, differing in the heterogeneity and
      native disulfide-bond content of their intermediates. Information from folding
      studies of these proteins, together with the recent structural determinations of
      predominant intermediates, has provided new molecular insights into oxidative
      folding and clarifies the major rules that govern it.

PMID- 16600599
TI  - To be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes.
AB  - Flavin-dependent enzymes catalyse a wide range of reactions and, thereby,
      facilitate a variety of cellular processes. Among the properties that equip
      flavoenzymes with this chemical versatility is their reactivity towards oxygen,
      which shows huge variation among flavoproteins. A survey of known 3D structures
      of flavin-dependent oxidases and dehydrogenases and the correlation with their
      functional properties indicates that there are no structural rules that enable
      prediction of whether or how a flavoenzyme reacts with oxygen. Combinations of
      subtle factors such as dipole pre-organization, charge distribution, dynamics and
      solvation in the active centre determine the balance of interactions that control
      oxygen reactivity. The chemical basis of oxygen reactivity remains a puzzling
      problem and represents one of the challenging questions in modern
      flavoenzymology.

PMID- 16600600
TI  - Comparison of calculated spectra for the interaction of photons in a liquid
      scintillator. Example of 54Mn 835 keV emission.
AB  - The CIEMAT/NIST and TDCR methods in liquid scintillation counting, initially
      developed for the activity standardization of pure-beta radionuclides, have been
      extended to the standardization of electron capture and beta-gamma radionuclides.
      Both methods require the calculation of the energy spectrum absorbed by the
      liquid scintillator. For radionuclides emitting X-rays or gamma-rays, when the
      energy is greater than a few tens of keV the Compton interaction is important and
      the absorption is not total. In this case, the spectrum absorbed by the
      scintillator must be calculated using analytical or stochastic models. An
      illustration of this problem is the standardization of 54Mn, which is a
      radionuclide decaying by electron capture. The gamma transition, very weakly
      converted, leads to the emission of an 835 keV photon. The calculation of the
      detection efficiency of this radionuclide requires the calculation of the energy
      spectrum transferred to the scintillator after the absorption of the gamma ray
      and the associated probability of absorption. The validity of the method is thus
      dependent on the correct calculation of the energy transferred to the
      scintillator. In order to compare the calculation results obtained using various
      calculation tools, and to provide the metrology community with some information
      on the choice of these tools, the LS working group of the ICRM organised a
      comparison of the calculated absorbed spectra for the 835 keV photon of 54Mn. The
      result is the spectrum of the energy absorbed by the scintillator per emission of
      an 835 keV gamma ray. This exercise was proposed for a standard 20 ml LS glass
      vial and for LS cocktail volumes of 10 and 15 ml. The calculation was done for
      two different cocktails: toluene and a widely used commercial cocktail, Ultima
      Gold. The paper describes the results obtained by nine participants using a total
      of 12 calculation codes.

PMID- 16600602
TI  - Experimental validation of coincidence summing corrections computed by the ETNA
      software.
AB  - The ETNA software has been developed to compute efficiency transfer and
      coincidence summing corrections. Different experiments are combined to test the
      validity of this last facility. Point sources with multi-gamma emitters are
      measured at several source-to-detector distances. Experimental correction factors
      are determined from the variation in the peaks' relative intensities versus the
      geometrical conditions. The ETNA code is used to compute the corrections due to
      coincidence summing for the same geometries. The calculated values are compared
      to the experimental ones.

PMID- 16600601
TI  - Kr-81m calibration factor for the npl ionisation chamber.
AB  - A general method has been developed for the measurement of the activity
      concentration of 81mKr gas. Due to its short half-life, 13.1s, this gas has to be
      eluted from a 81Rb/81mKr generator. The 81Rb parent has a half-life of about 4.6
      h. The calibration was done in two steps: firstly, a gamma-ray spectrometer was
      calibrated using 51Cr and 139Ce sources, nuclides with gamma-ray energies
      bracketing that of 81mKr (190.5 keV). The measurement geometry was equivalent to
      that of the 81mKr measurement; the sources were inserted into two collimated PTFE
      tubes in front of the gamma-ray detector. Secondly, a calibration factor for the
      NPL radionuclide calibrator was determined with a specially designed ionisation
      chamber insert. The 81mKr gas passed in front of the gamma-ray detector in PTFE
      tubing before and after entering the ionisation chamber. The calibration factor
      for 81mKr in the radionuclide calibrator with this geometry was independent of
      the gas flow rate within determined limits. The analytical calculations of the
      activity determination, uncertainties and measurement criteria are discussed.

PMID- 16600603
TI  - Photon-photon coincidences for activity determination: I-125 and other
      radionuclides.
AB  - Theory and experiment of photon-photon coincidence counting with distance
      variation for activity standardisation of radionuclide solutions are described.
      The activity of an I-125 solution from an international comparison organised by
      the BIPM in 2004 was determined. The value obtained agrees with other methods
      within a limit of 0.2%. The extension of this activity standardisation method to
      other radionuclides such as Cd-109 with I-125 as a tracer nuclide, In-111, Am-241
      and I-124 with a radionuclidic impurity of I-125 is studied. Achieved
      uncertainties of the activities of Cd-109 and In-111 are of the order of 1.5%.
      The activity values of sources of Am-241 are determined relative to each other.
      Am-241 is used for checking the measuring system and as a long-lived reference
      source. After decay of the order of several I-124 half-lives, sources of I-124
      with I-125 are measured to determine the I-125 activity portion.

PMID- 16600604
TI  - Radionuclide metrology in the life sciences: recent advances and future trends.
AB  - This paper reviews activities in the field of radionuclide metrology applied to
      the life sciences between the years 2000 and 2005. The requirements for accuracy
      and consistency in making radioactivity measurements in radiation medicine,
      coupled with an increased awareness of the role of measurement standards in
      quality assurance programmes, has prompted a great deal of research in this area.
      During the past 5 years, particular emphasis has been on: (1) the development of
      primary standards for radionuclides, (2) development of secondary/transfer
      standards, (3) development of radionuclide standards for brachytherapy, and (4)
      inter-laboratory comparisons at the end-user level. Activities carried out by
      National Metrology Institutions in these areas are reviewed and a look at future
      trends is presented.

PMID- 16600606
TI  - Unusual cause of myocardial ischemia noninvasively assessed with ECG-gated
      computed tomography coronary angiography.

PMID- 16600605
TI  - Half-life evaluations for 3H, 90Sr, and 90Y.
AB  - A recent paper has reviewed methods for the evaluation of discrepant sets of data
      and demonstrated the results of applying these methods to the published half-life
      data of 90Sr and 137Cs [MacMahon, T.D., Pearce, A., Harris, P., 2004. Convergence
      of techniques for the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275
      281]. The half-life data for 3H has been subject to a comprehensive review and
      critical evaluation by Lucas and Unterweger [2000. Comprehensive review and
      critical evaluation of the half-life of tritium. J. Res. Natl. Inst. Stand.
      Technol. 105, 541-549]. The current paper reports the results of applying the
      various evaluation procedures of MacMahon et al. Convergence of techniques for
      the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275-281] to the data
      of Lucas and Unterweger [Comprehensive review and critical evaluation of the half
      life of tritium. J. Res. Natl. Inst. Stand. Technol. 105, 541-549], resulting in
      a recommended half-life of 4497(4) days. MacMahon et al. [Convergence of
      techniques for the evaluation of discrepant data. Appl. Radiat. Isot. 60, 275
      281] highlighted problems in the evaluation of the discrepant half-life data of
      90Sr, in particular the worrying upward trend in the data, where the weighted
      mean of all the measurements increases, on average, by 35 days each time a new
      measurement result is added. The current paper reports on further analyses of
      these data. New measurements of the half-life of 90Y have been reported by
      Kossert and Schrader [2004. Standardization by liquid scintillation counting and
      half-life measurements of 90Y. Appl. Radiat. Isot. 60, 741]. This has prompted a
      new evaluation of all available published 90Y half-life data. The data are fairly
      consistent, and a value of 64.063(16) h is recommended.

PMID- 16600607
TI  - Thoracoscopic treatment of pulmonary sequestration.
AB  - OBJECTIVE: Pulmonary sequestration is a rare congenital malformation and may be
      the cause of recurrent infections or hemoptysis. It has been shown in case
      reports that resection by video-assisted thoracic surgery (VATS) is feasible
      despite the possible technical difficulties due to inflammatory changes, but its
      role has not been evaluated yet in a larger series of consecutively treated
      patients. METHODS: Retrospective analysis of all consecutively thoracoscopically
      treated patients (between January 1991 and January 2005) with pulmonary
      sequestration in a single center. We included 14 patients in the study who
      fulfilled the criteria; seven were women. Median age was 33 years (20-64 years).
      The following data were analyzed for all patients: major symptoms, diagnostic
      procedures, treatment, and outcome. Operative parameters and findings including
      operating time, blood loss, anatomical location of the sequestration, and feeding
      vessels were evaluated. RESULTS: Leading symptoms were recurrent infections (10),
      hemoptysis (3), and chest discomfort (1). The diagnosis was made by CT scan.
      Additionally, an arteriography or an angio-MRI was done in three patients and one
      patient, respectively. Thirteen intralobar (all lower lobes, eight on the right)
      and one left-sided extralobar pulmonary sequestration were resected. We performed
      eight lobectomies, four atypical segmentectomies, one extralobar resection, and
      one occlusion of the aberrant artery. One case had to be converted to a
      thoracotomy due to bleeding from the aberrant artery. There was no mortality.
      Complications included pneumonia in three cases, one hemothorax, one pneumothorax
      after removing the chest tube, and one wound infection. All were treated
      conservatively. CONCLUSION: Thoracoscopic treatment of pulmonary sequestration is
      feasible in experienced hands. The aberrant systemic artery can be freed and
      dissected safely despite the frequently occurring inflammatory changes.
      Conversion rate to thoracotomy is low.

PMID- 16600608
TI  - Intradiaphragmatic bronchogenic cyst.

PMID- 16600609
TI  - Do we need the new Italian risk stratification model for CABG patients?

PMID- 16600612
TI  - Diagnosis and prognosis of traumatic pulmonary psuedocysts: a review of 12 cases.
AB  - BACKGROUND: Traumatic pulmonary pseudocysts or post-traumatic pneumatocoeles are
      a relatively rare-encountered condition occurring after trauma and an even rarer
      talked about subject. Most resolve within a few weeks, but if complicated by
      hematoma, may persist for months. This study intends to evaluate the resolution
      times of traumatic pulmonary pseudocysts and their clinical significance.
      METHODS: We report a case analysis of 12 cases from Hanyang University Guri
      Hospital dating from July 1997 through October 2004. RESULTS: The overall mean
      time for complete resolution was 85.6 days. The mean time for resolution for the
      uncomplicated traumatic pulmonary pseudocysts was 25.3 days (n=6) and the mean
      time for resolution for the complicated (blood filled) traumatic pulmonary
      pseudocysts was 145.8 days (n=6). When resolution times were compared according
      to size, those less than 2 cm showed a mean resolution time of 23.6 days (n=5)
      and those greater than or equal to 2 cm showed a mean resolution time of 129.9
      days (n=7). CONCLUSIONS: Comparisons between completely blood-filled pseudocysts
      and uncomplicated pseudocysts have shown statistically significant differences in
      resolution times. Statistical significance has also been found between
      pseudocysts of sizes less than 2 cm and those greater than or equal to 2 cm.
      Conservative treatment is generally the rule; close follow-up and symptomatic
      treatment are necessary.

PMID- 16600613
TI  - Cardiac transplantation following ACORN CorCap device implantation.
AB  - Passive ventricular restraint devices, such as the ACORN CorCap, have been
      introduced as a potential therapy for congestive heart failure (CHF). These mesh
      devices act as a mechanical support for the dilated heart. Due to incorporation
      of the device to the epicardium, concerns about the feasibility of reoperation
      following CorCap placement have been raised. This case illustrates that although
      technically challenging, reoperation for heart transplantation after CorCap
      implantation is feasible and safe.

PMID- 16600615
TI  - Swan-Ganz bipolar pacing catheter entrapment in the tricuspid valve apparatus.

PMID- 16600616
TI  - Transapical approach for sutureless stent-fixed aortic valve implantation:
      experimental results.
AB  - OBJECTIVE: Percutaneous aortic valve implantation has been performed in patients
      with severe aortic stenosis judged as nonsurgical candidates. We evaluated a
      facilitated transapical antegrade approach for potential use in surgical high
      risk patients. METHODS: A pericardial xenograft fixed within a 23-mm stent
      (Cribier-Edwards aortic prosthesis, Edwards Inc., Irvine, CA, USA) was implanted
      using a transapical approach in fifteen 35-45 kg pigs. A limited or a full
      sternotomy was used to transapically introduce a crimped valve through a 24-F
      sheath. Deployments were performed on the beating heart either with ventricular
      unloading using femoro-femoral cardiopulmonary bypass (CPB) or rapid ventricular
      pacing (RVP), all under fluoroscopic and echocardiographic visualization.
      RESULTS: All valves were successfully deployed at the target site with acceptable
      visualization of the noncalcified annulus. Valve migration occurred in six
      procedures (three distal and three retrograde) secondary to inadequate reduction
      of ventricular output, unfavorable annular anatomy, excessive crimping of the
      valve, and dislodgement by the delivery balloon. Exact positioning of the valve
      into the target area was confirmed by autopsy at the end of the procedures.
      Paravalvular leak was noted in five implants. CONCLUSIONS: The transapical
      approach provides a safe, accurate, and effective route for facilitated antegrade
      delivery of a stent-fixed valve. Advanced stent design will lead to better
      stability of the implant and may minimize the risk of paravalvular leakage in
      future. Identifying the appropriate population for human feasibility trials
      remains a challenge.

PMID- 16600617
TI  - Genetic testing for hereditary cancers: the impact of gender on interest, uptake
      and ethical considerations.
AB  - Genetic testing promises earlier intervention and more successful outcomes for
      individuals at risk for hereditary breast/ovarian and colorectal cancer. Research
      shows that gender influences health and access to health care services. In this
      paper, we review theoretical issues of gender, and research outcomes, in relation
      to genetic testing for hereditary cancers. We argue that integrating a gender
      analysis into assessment of new technologies and health programs is necessary to
      improve appropriateness, accessibility and effectiveness. Attention to gender is
      also critical to developing a deeper understanding of the ethical issues (both
      benefits and harms) raised by new genetic technologies.

PMID- 16600618
TI  - Angiogenesis and cancer: A cross-talk between basic science and clinical trials
      (the "do ut des" paradigm).
AB  - Angiogenesis plays a crucial role in facilitating tumor growth and the metastatic
      process, and it is the result of a dynamic balance between pro-angiogenic
      factors, like vascular endothelial growth factor (VEGF) and platelet-derived
      growth factor, and antiangiogenic factors, like thrombospondin-1 and angiostatin.
      Many drugs that target human tumors, like bevacizumab and some VEGF-receptor
      tyrosine-kinase inhibitors (e.g., BAY 43-9006, SU11248 and PTK787/ZK222584) have
      been studied in clinical trials, with favorable toxicity reports and encouraging
      results in advanced colorectal cancer, renal cell cancer, breast cancer and non
      squamous non-small cell lung cancer, either combined with chemotherapy, or in
      monotherapy. Another potential approach to inhibiting angiogenesis is through
      metronomic chemotherapy (low doses of chemotherapy for long periods of time).
      This review describes the mechanisms of the angiogenic process and evaluates the
      recent data about antiangiogenic therapies in clinical trials.

PMID- 16600619
TI  - Mechanisms of chromosome instability in cancers.
AB  - Most tumours arise through clonal selection and waves of expansion of a somatic
      cell that has acquired genetic alterations in essential genes either controlling
      cell death or cell proliferation. Furthermore, stability of the genome in cancer
      cells becomes precarious and compromised because several cancer-predisposing
      mutations affect genes that are responsible for maintaining the integrity and
      number of chromosomes during cell division. Consequently, the archetypical
      transformation in tumour cells results in aneuploidy. Indeed, almost all tumour
      cells display a host of karyotype alterations, showing translocations, gains or
      losses of entire or large parts of chromosomes. Cancers do not necessarily have a
      higher mutation rate than normal tissue at the nucleotide level, unless they have
      gained a mutator phenotype through exposure to environmental stress, but rather
      exhibit gross chromosomal changes. Therefore, it appears that the main mechanism
      of tumour progression stems from chromosome instability. Chromosomal instability
      prevailing in tumour cells arises through several different pathways and is
      probably controlled by hundreds of genes. Therefore, this review describes the
      main factors that control chromosome stability through telomere maintenance,
      mechanisms of cell division, and the mitotic checkpoints that govern centrosome
      duplication and correct chromosome segregation.

PMID- 16600620
TI  - Reversible binding of celecoxib and valdecoxib with human serum albumin using
      fluorescence spectroscopic technique.
AB  - Mechanism of interaction of non-steroidal anti-inflammatory drugs, celecoxib and
      valdecoxib with human serum albumin has been studied using fluorescence
      spectroscopic technique. There was only one high affinity site on serum albumin
      for both the drugs with association constants of the order of 10(4) in the case
      of celecoxib and 10(5) in the case of valdecoxib. Thermodynamic parameters for
      the binding indicated that hydrogen bonding interactions are predominantly
      involved in the binding of these drugs to human serum albumin. Binding studies in
      the presence of hydrophobic probe, 1-anilinonaphthalene-8-sulfonate (ANS)
      suggested that the mode of interaction of drugs and ANS with HSA is different and
      hydrophobic interactions are not primarily involved in the binding. Studies
      carried out in the presence of site-specific probe showed that drugs are bound at
      site II and phenolic oxygen of (411)Tyr is involved in binding. Stern-Volmer
      analysis of the quenching data indicated that predominantly static quenching
      mechanism is operative and the tryptophan residues of albumin are fully
      accessible to celecoxib and only partially accessible to valdecoxib. The presence
      of salt caused a decrease in the association constant and significant increase in
      the concentration of free drug.

PMID- 16600621
TI  - Rehmannia glutinosa induces glial cell line-derived neurotrophic factor gene
      expression in astroglial cells via cPKC and ERK1/2 pathways independently.
AB  - Among four herbs of traditional Chinese medicines (TCMs) used in the therapy of
      dementia, Rehmannia glutinosa (RG) was found to induce the gene expression of
      glial cell line-derived neurotrophic factor (GDNF) in C6 glioblastoma cells and
      primary cultured astrocytes. The RG-induced GDNF mRNA up-regulation in C6
      glioblastoma cells was completely attenuated by the presence of a pan-specific
      protein kinase C (PKC) inhibitor (Ro-31-8220) and a MAPK/ERK kinase 1 (MEK1)
      inhibitor (U0126). A conventional PKC inhibitor (Go6976) also significantly
      decreased GDNF gene induction. On the other hand, RG treatment was found to
      stimulate phosphorylation of extracellular signal-regulated kinase 1 and 2
      (ERK1/2), which preceded GDNF mRNA induction in C6 glioblastoma cells. However,
      none of the PKC inhibitors significantly changed RG-stimulated ERK1/2
      phosphorylation. Therefore, RG-stimulated GDNF gene expression could be
      independently up-regulated through cPKC and ERK 1/2 pathways in C6 glioblastoma
      cells.

PMID- 16600622
TI  - Positive electrospray ion trap multistage mass spectrometric fragmentation of
      synthetic analogs of saccharide part of lipopolysaccharides of Vibrio cholerae
      O:1.
AB  - Oligosaccharides (mono- to hexamers) that mimic the terminal epitopes of O
      antigens of Vibrio cholerae O:1, serotypes Ogawa and Inaba, have been studied by
      electrospray ion trap (ESI IT) mass spectrometry. Sodium or potassium-cationized
      adducts are characteristic ions under the conditions of ESI-MS analysis. The
      tentative pathways of fragmentation have been proven by multistage ion trap MS
      (MS(n), n = 1-3). The predominant pathway of fragmentation of the oligomers is
      the neutral loss of monosaccharide residue shortening the length of the
      oligosaccharide. In this way, conversion of the Ogawa to Inaba fragments takes
      place under the conditions of measurement. ESI MS/MS provided sufficient
      information about molecular mass, the number of saccharide residues, and the
      structure of saccharides, about the C (4)-amide of 3-deoxy-L-glycero-tetronic
      acid (DGT) of the compounds investigated, and allows to distinguish between Ogawa
      and Inaba serotypes.

PMID- 16600623
TI  - Long stretches of sequential and identical serine or alanine codons are
      compatible with an efficient full-length protein expression in Escherichia coli.
AB  - The Schistosoma japonicum glutathione S-transferase (GST) recombinant cDNAs,
      carrying blocks of sequential and identical triplets, consisting of 15-30-45 GCT
      (Ala) codons or 15-30 and also up to 75 AGC (Ser) codons, are expressed
      efficiently in an Escherichia coli system in the form of full-length protein
      chains, as detected by Coomassie-stained SDS-polyacrylamide gels, and soluble
      fusion proteins are purified by GSH-affinity chromatography. High expression
      levels and high yields of purified recombinant proteins are achieved. The
      efficient protein expression is independent of the molecular context and position
      of the polySer/polyAla string inserted into the GST carrier (near the part of the
      gene encoding the N- or the C-terminus). These findings suggest that E. coli is a
      powerful biological system to express foreign genes carrying long stretches
      coding for Ser- or Ala-rich domains, which are not uncommon in eukaryotic
      proteins. Moreover, data reported here show that the negative effect of
      sequential serine codons on protein expression in bacteria, previously reported
      in the literature, is not a general phenomenon.

PMID- 16600624
TI  - Construction, purification, and immunogenicity of recombinant cystein-cystein
      type chemokine receptor 5 vaccine.
AB  - Cystein-Cystein type chemokine receptor 5 (CCR5) is a seven-transmembrane, G
      protein coupled receptor. It is a major coreceptor with CD4 glycoprotein
      mediating cellular entry of CCR5 strains of HIV-1. A lack of cell-surface
      expression of CCR5 found in the homozygous Delta32 CCR5 mutation, upregulation of
      CC chemokines and antibodies to CCR5 are associated with resistance to HIV
      infection. In addition, CCR5 can be blocked by three CC chemokines and antibodies
      to three extracellular domains of CCR5. Consequently, CCR5 is considered an
      attractive therapeutic target against HIV infection. In the current study, we
      constructed a recombinant vaccine by coupling a T helper epitope AKFVAAWTLKAA
      (PADRE) to the N terminus of CCR5 extracellular domains (PADRE-CCR5) and
      expressed this protein in Escherichia coli. We have developed an inexpensive and
      scalable purification process for the fusion protein from inclusion bodies and
      the final yields of 6mg purified fusion protein per gram of cell paste was
      obtained. The immunogenicity of the recombinant vaccine generated was examined in
      BALB/c mice. Sera from the vaccinated mice demonstrated high-titer specific
      antibodies to the recombinant vaccine, suggesting that PADRE-rCCR5 may be used as
      a candidate of active CCR5 vaccine.

PMID- 16600625
TI  - The production of cleaved, trimeric human immunodeficiency virus type 1 (HIV-1)
      envelope glycoprotein vaccine antigens and infectious pseudoviruses using linear
      polyethylenimine as a transfection reagent.
AB  - Trimeric HIV-1 envelope glycoproteins (Env) are now being evaluated instead of
      monomeric gp120 as vaccine antigens because they mimic more closely the spikes
      expressed on the surface of virions. Thus, it can be argued that trimers have a
      more native structure than gp120, so might be superior at raising neutralizing
      antibodies. One approach to making Env trimers is to ensure that they are cleaved
      at the gp120-gp41 border, but stabilized by other, engineered substitutions such
      as intra-subunit disulfide bonds (SOS and SOSIP gp140 proteins). However, the
      production of properly folded, cleaved trimers is complicated by the requirement
      for co-expression of the exogenous protease furin, to facilitate the efficient
      processing oft the gp120-gp41 cleavage site. Also, yields of purified trimeric
      SOSIP gp140 proteins are usually moderate and for scale-up procedures the cost of
      transfection reagents becomes an important economical factor. Here, we assess the
      optimal culture conditions for the transient expression of these complex
      proteins. We found that the use of linear polyethylenimine 25 kDa (PEI25k) as a
      transfection aid was a cost-efficient, economical alternative to several
      commercially available products. By using PEI25k and an optimized plasmid:furin
      ratio, we could express proteolytically mature, trimeric Env vaccine antigens at
      levels high enough for use in immunization or structural studies. We also show
      that the same transfection method can be used to generate infectious
      pseudoviruses.

PMID- 16600626
TI  - Cloning, expression, purification, and characterization of Leishmania major
      dihydroorotate dehydrogenase.
AB  - Leishmania major Friedlin (LmjF) is a protozoan parasite whose genomic sequence
      has been recently elucidated. Here we have cloned, overexpressed, purified, and
      characterized the product of the gene from LmjF chromosome 16: LmjF16.0530, which
      encodes a protein with putative dihydroorotate dehydrogenase activity.
      Dihydroorotate dehydrogenase (DHODH) is a flavoprotein that catalyses the
      oxidation of L-dihydroorotate to orotate, the fourth sequential step in the de
      novo pyrimidine nucleotide synthesis pathway. The predicted enzyme from L. major
      was cloned and expressed in Escherichia coli strain BL21(DE3) as a histidine-tag
      fusion protein and purified to homogeneity using affinity chromatography. The
      final product was homogeneous in SDS-PAGE gel electrophoresis. The dihydroorotate
      oxidase activity has been assayed and the steady-state kinetic mechanism has been
      determined using fumarate as the oxidizing substrate. The catalysis by LmDHODH
      enzyme proceeds by a Ping-Pong Bi-Bi mechanism and the kinetic parameters Km were
      calculated to be 90 and 418 microM for dihydroorotate and fumarate, respectively,
      and Vmax was calculated to be 11 micromol min-1 mg-1. Our results confirmed that
      the product of the gene LmjF16.0530, whose function has previously been predicted
      based on homology to known proteins, can therefore be positively assigned as L.
      major DHODH.

PMID- 16600627
TI  - A novel fusion protein system for the production of native human pepsinogen in
      the bacterial periplasm.
AB  - Human pepsinogen is the secreted inactive precursor of pepsin. Under the acidic
      conditions present in the stomach it is autocatalytically cleaved into the active
      protease. Pepsinogen contains three consecutive disulfides, and was used here as
      a model protein to investigate the production of aspartic proteases in the
      Escherichia coli periplasm. Various N-terminal translocation signals were applied
      and several different expression vectors were tested. After fusion to pelB, dsbA
      or ompT signal peptides no recombinant product could be obtained in the periplasm
      using the T7 promoter. As a new approach, human pepsinogen was fused to E. coli
      ecotin (E. coli trypsin inhibitor), which is a periplasmic homodimeric protein of
      142 amino acids per monomer containing one disulfide bridge. The fusion protein
      was expressed in pTrc99a. After induction, the ecotin-pepsinogen fusion protein
      was translocated into the periplasm and the ecotin signal peptide was cleaved.
      Upon acid treatment, the fusion protein was converted into pepsin, indicating
      that pepsinogen was produced in its native form. In shake flasks experiments, the
      amount of active fusion protein present in the periplasm was 100 microg per litre
      OD 1, corresponding to 70 microg pepsinogen. After large scale cultivation, the
      fusion protein was isolated from the periplasmic extract. It was purified to
      homogeneity with a yield of 20%. The purified protein was native. Acid-induced
      activation of the fusion protein proceeded very fast. As soon as pepsin was
      present, the ecotin part of the fusion protein was rapidly digested, followed by
      a further activation of pepsinogen.

PMID- 16600628
TI  - Development of the system ensuring a high-level expression of hepatitis C virus
      nonstructural NS5B and NS5A proteins.
AB  - The plasmid pET-21d-2c-5BDelta55 effectively expressing a C-terminally truncated
      form (NS5BDelta55) of the hepatitis C virus (HCV) RNA-dependent RNA polymerase
      (RdRp) was constructed. It was derived from pET-21d-5BDelta55 plasmid and
      contained six mutations in the ATG-start codon region and an additional cistron
      upstream the target gene. The C-terminally His-tagged NS5BDelta55 protein was
      expressed in Rosetta(DE3) Escherichia coli strain bearing an additional pRARE
      plasmid encoding extra copies of rare tRNAs. The yield of the target enzyme
      exceeded by a factor of 29 the yield of NS5BDelta55 protein expressed from the
      parental pET-21d-5BDelta55 plasmid (5 mg/L). The increase in the protein yield
      could be explained by facilitated protein translation initiation, resulted from
      disruption of the stable secondary mRNA structure. The pET-21d-2c-5BDelta55
      plasmid yielded one third amount of the protein when expressed in BL-21(DE3)
      strain, indicating that the pRARE plasmid is required for a high-level expression
      of NS5BDelta55 protein. The 29-fold enhancement of the protein yield was
      accompanied by only a 2.5-fold increase of the corresponding mRNA level. The
      expression of another HCV NS5A protein His-tagged at the C-terminus in the
      developed system yielded a similar amount of the protein (4 mg/L), whereas its N
      terminally His-tagged counterpart was obtained in a 30 mg/L yield. The NS5A
      protein purified under denaturing conditions and renatured in solution inhibited
      the HCV RdRp and was a substrate for human casein kinase II.

PMID- 16600629
TI  - Purification and application of bacterially expressed chimeric protein E1E2 of
      hepatitis C virus.
AB  - E1 and E2 glycoproteins are structural components of hepatitis C virus (HCV)
      virion. They are involved in cellular receptors interaction, neutralising
      antibodies elicitation, and viral morphogenesis. They are considered as major
      candidates for anti-HCV vaccine. In this report, we first expressed tandem E1E2
      as well as C-terminally truncated E1 fragment and C-terminally truncated E2
      fragment, respectively, in Escherichia coli cells and the proteins were purified
      to homogenesis. All the purified proteins can react specifically with patient
      sera. Both purified chimeric protein E1E2 and protein E2 can interact with a
      putative cellular receptor CD81, while purified protein E1 cannot interact with
      CD81. The sera of rabbit immunized with the E1E2 inhibited the binding of E2
      protein to the major extracellular loop of human CD81 and reacted with both
      proteins E1 and E2, respectively. Anti-E1 and E2 antibodies can be generated
      simultaneously in the rabbit immunized with the E1E2, and the titers of
      antibodies were 63 or 56% higher than the titers induced by E1 or E2 alone,
      respectively. The results suggest that E1 and E2 can enhance their immunogenicity
      each other in chimeric protein E1E2 and the E. coli-derived chimeric protein E1E2
      and corresponding antisera can be used as an useful tools in anti-HCV vaccine
      research.

PMID- 16600630
TI  - Purification, characterization, and crystallization of human pyrroline-5
      carboxylate reductase.
AB  - Pyrroline-5-carboxylate reductase (P5CR) catalyzes the reduction of Delta1
      pyrroline-5-carboxylate (P5C) to proline with concomitant oxidation of NAD(P)H to
      NAD(P)(+). The enzymatic cycle between P5C and proline is very important in many
      physiological and pathological processes. Human P5CR was over-expressed in
      Escherichia coli and purified to homogeneity by chromatography. Enzymatic assays
      of the wild-type protein were carried out using 3,4-dehydro-L-proline as
      substrate and NAD(+) as cofactor. The homopolymer was characterized by cross
      linking and size exclusion gel filtration chromatography. Human P5CR was
      crystallized by the hanging-drop vapor-diffusion method at 37 degrees C.
      Diffraction data were obtained to a resolution of 2.8A and were suitable for high
      resolution X-ray structure determination.

PMID- 16600631
TI  - Expression optimization and purification process development of an engineered
      soluble recombinant mouse linker of activation of T cells using surface enhanced
      laser desorption/ionization-mass spectrometry.
AB  - Protein purification development is the bottleneck of recombinant protein
      production therefore there is a need to shorten process development and
      monitoring. Surface enhanced laser desorption/ionization-mass spectrometry (SELDI
      MS) was evaluated to optimize the expression and to develop the purification of a
      recombinant mouse protein: a transmembrane adaptor involved in T cell receptor
      signaling named "linker for activation of T cells" (LAT). The protein was
      expressed as a soluble form (S-LAT) in three strains of Escherichia coli: BL21
      (DE3), Rosetta (DE3), and BL21 (DE3) pLys S. The expression of S-LAT was
      monitored on immobilized metal affinity chromatography (IMAC) ProteinChip arrays.
      The highest level of expression was found in Rosetta (DE3) with a C-terminal
      construct after induction at 37 degrees C. The purification scheme was elucidated
      using SELDI-MS: S-LAT was efficiently captured on an IMAC ProteinChip array
      saturated with nickel ions (Ni(2+)) and then fractionated on a Q ProteinChip
      array. These conditions were directly transferred to IMAC-Ni(2+) HyperCel and Q
      Ceramic HyperD F chromatography sorbents. After these two purification steps, S
      LAT was estimated to be more than 80% pure, confirming a very good match between
      array and sorbent. Finally, a peptide mapping was performed on a hydrophobic
      array after in gel trypsin digest, verifying that the purified protein was the
      mouse LAT. This is the first report of a protocol for the production and
      purification of S-LAT. The selection of the best expression and purification
      strategy along with the identification were enabled in 5 days with less than 5 mL
      of soluble fraction of crude culture samples.

PMID- 16600632
TI  - Observing growth steps of collagen self-assembly by time-lapse high-resolution
      atomic force microscopy.
AB  - Insights into molecular mechanisms of collagen assembly are important for
      understanding countless biological processes and at the same time a prerequisite
      for many biotechnological and medical applications. In this work, the self
      assembly of collagen type I molecules into fibrils could be directly observed
      using time-lapse atomic force microscopy (AFM). The smallest isolated fibrillar
      structures initiating fibril growth showed a thickness of approximately 1.5 nm
      corresponding to that of a single collagen molecule. Fibrils assembled in vitro
      established an axial D-periodicity of approximately 67 nm such as typically
      observed for in vivo assembled collagen fibrils from tendon. At given collagen
      concentrations of the buffer solution the fibrils showed constant lateral and
      longitudinal growth rates. Single fibrils continuously grew and fused with each
      other until the supporting surface was completely covered by a nanoscopically
      well-defined collagen matrix. Their thickness of approximately 3 nm suggests that
      the fibrils were build from laterally assembled collagen microfibrils. Laterally
      the fibrils grew in steps of approximately 4 nm, indicating microfibril formation
      and incorporation. Thus, we suggest collagen fibrils assembling in a two-step
      process. In a first step, collagen molecules assemble with each other. In the
      second step, these molecules then rearrange into microfibrils which form the
      building blocks of collagen fibrils. High-resolution AFM topographs revealed
      substructural details of the D-band architecture of the fibrils forming the
      collagen matrix. These substructures correlated well with those revealed from
      positively stained collagen fibers imaged by transmission electron microscopy.

PMID- 16600633
TI  - The composition and structure of bovine peritubular dentin: mapping by time of
      flight secondary ion mass spectroscopy.
AB  - The dentin layer of the tooth is a complex mineralized tissue traversed by a
      closely packed system of tubules. Each tubule is surrounded by highly mineralized
      tissue referred to as peritubular dentin (PTD). The remaining mineralized
      collagen network between the tubules is the intertubular dentin (ITD). A TOF-SIMS
      analysis of the PTD constituents has been used to compare the PTD to the ITD. The
      PTD differs from the ITD not only in the degree of mineralization but also in the
      amount and nature of the mineral elements and amino acids. The organic matrix of
      the PTD consists of a unique collagen free assembly of proteins rich in glutamic
      acid, where the ITD organic matrix is collagen-rich and Asp-rich. The apparent
      concentration of organic fragment ions observed in the PTD in the TOF-SIMS
      negative ion mode was much higher than expected. The PTD was found to be rich in
      Ca2+, Na+, Mg2+, and K+. The amount of Mg2+ and K+ in the PTD was significantly
      reduced after deproteination, while Ca2+ and Na+ were still accumulated in the
      PTD. This implies that Mg2+ and K+ are mainly associated with the organic matrix
      rather than with the mineral of the PTD.

PMID- 16600634
TI  - Membrane-protein stability in a phospholipid-based crystallization medium.
AB  - Protein stability is a crucial factor to consider when attempting to crystallize
      integral membrane proteins. Cubic phase, or in meso, lipid-bilayer
      crystallization media are thought to provide native-like environments that should
      facilitate membrane protein crystallization by helping to stabilize the native
      protein conformation for the duration of the crystallization process. While
      excellent crystals of bacteriorhodopsin (bR) and other Halobacterial rhodopsins
      have been obtained in lipid-bilayer gels formed with monoglycerides, success
      remains elusive in the general application of such media to other membrane
      proteins. Additionally, we have noted that some mutants of bR are highly unstable
      in gels formed with monoolein. Phosphatidylethanolamines (PE) and derivatives of
      PE represent another class of lipids that can form connected-bilayer gels. When
      wildtype bR and a labile bR mutant were reconstituted into this phospholipid gel,
      spectroscopy showed that the protein is both more stable and has improved
      conformational homogeneity as compared to gels formed using monoolein. In
      addition, we demonstrate that well-diffracting crystals of bR can be grown from a
      PE-based crystallization medium. Since most proteins lack a stability-indicating
      chromophore and other structure-based analytical techniques are poorly compatible
      with the lipid gel, we developed a generally-applicable spectroscopic technique
      based on the intrinsic fluorescence of tryptophan residues. This fluorescence
      assay makes possible the rapid evaluation of lipid gels as media for the
      crystallization of membrane proteins.

PMID- 16600635
TI  - Crystal structure of human pyridoxal kinase.
AB  - Pyridoxal kinase, a member of the ribokinase superfamily, catalyzes the ATP
      dependent phosphorylation reaction of vitamin B6 and is an essential enzyme in
      the formation of pyridoxal-5'-phosphate, a key cofactor for over 100 enzymes.
      Pyridoxal kinase is thus regarded as a potential target for pharmacological
      agents. In this paper, we report the 2.8 angstroms crystal structure of human
      pyridoxal kinase (HPLK) expressed in Escherichia coli. The diffraction data
      revealed unexpected merohedral perfect twinning along the crystallographic c
      axis. Taking perfect twinning into account, the structure in dimeric form was
      well refined according to the CNS program. Structure comparison reveals that the
      key 12-residue peptide over the active site in HPLK is a beta-strand/loop/beta
      strand flap, while the corresponding peptide in sheep brain enzyme adopts a loop
      conformation. Moreover, HPLK possesses a more hydrophobic ATP-binding pocket.
      This structure will facilitate further biochemical studies and structure-based
      design of drugs related to pyridoxal kinase.

PMID- 16600636
TI  - Work to rest durations ratios exceeding unity are a risk factor for low back
      disorder; a feline model.
AB  - Low back disorders are prominent among the work force engaged in static anterior
      flexion during the workday. As a continuing part of a long-term research aimed to
      identify the biomechanical and physiological processes and corresponding risk
      factors leading to such cumulative trauma disorder (CTD), we ventured to assess
      the effect of rest and the work-to-rest duration ratios that may prevent CTD.
      Three groups of the feline model were subjected to three load/rest paradigms: two
      30 min loading periods spaced by 10 min rest in Group I, two 30 min loading
      period spaced by 30 min rest in Group II and one 60 min loading period for Group
      III. The cumulative loading duration in the three groups was 60 min. Each of the
      groups were allowed 7h of rest while monitoring EMG and lumbar viscoelastic
      tissue creep each hour. The results demonstrate that for two 30 min load periods
      with a 30 min in between rest, an acute neuromuscular disorder was not present
      whereas for two 30 min loading with a 10 min rest it was. Similarly, for a 60 min
      loading with long-term rest, the disorder was present. Post hoc Fisher analysis
      demonstrated significant differences in the delayed hyperexcitability between the
      first and second group (P<0.0001) and the third and second (P<0.0001) group.
      Statistical difference in the displacement data of the three groups was not
      present. ANOVA showed a significant effect of time post-loading (P<0.0001 and
      different rest durations (P<0.0001) on the EMG data during the 7h recovery. The
      new data allow us to conclude that a work-to-rest duration ratio of 1:1 can
      prevent the development of CTD as long as the work periods are not too long (<60
      min). Longer static flexion durations do not respond favorably to rest even if it
      is of equal or longer duration. It is suggested that appropriate durations of
      rest may be a viable tool to avert CTD in a certain range whereas long static
      flexion durations should be avoided at all cost.

PMID- 16600637
TI  - Pre-landing muscle timing and post-landing effects of falling with continuous
      vision and in blindfold conditions.
AB  - The present study examined the effect of continuous vision and its occlusion in
      timing of pre-landing actions during free falls. When vision is occluded, muscle
      activation is hypothesized to start relative to onset of the fall. However, when
      continuous vision is available onset of action is hypothesized to be relative to
      the moment of touchdown. Six subjects performed 6 randomized sets of 6 trials
      after becoming familiar with the task. The 36 trials were divided in 2 visual
      conditions (vision and blindfold) and 3 heights of fall (15, 45 and 75 cm). EMG
      activity was recorded from the gastrocnemius and rectus femoris muscles during
      the falls. The latency of onset (L(o)) and the lapse from EMG onset to touchdown
      (T(c)) were obtained from these muscles. Vertical forces were recorded to assess
      the effects of pre-landing activity on the impacts at collision with and without
      continuous vision. Peak amplitude (F(max)), time to peak (T(max)) and peak
      impulse normalized to momentum (I(norm)) were used as outcome measures. Within
      flight time ranges of approximately 50-400 ms, the results showed that L(o) and
      T(c) follow a similar linear trend whether continuous vision was available or
      occluded. However, the variability of T(c) for each of the muscles was larger in
      the vision occluded condition. Analyses of variance showed that the rectus
      femoris muscle started consistently earlier in no vision trials. Finally, impact
      forces were not different in vision or blindfold conditions, and thus, they were
      not affected by minor differences in the timing of muscles prior to landing.
      Thus, it appears that knowing the surroundings before falling may help to reduce
      the need for a continuous visual input. The relevance of such input cannot be
      ruled out for falls from high landing heights, but cognitive factors (e.g.,
      attention to specific cues and anticipation of a fall) may play a dominant role
      in timing actions during short duration falls encountered daily.

PMID- 16600638
TI  - Force dynamic response of tibialis anterior-ankle joint unit in humans.
AB  - The aim of this study was to estimate the dynamic response of a human muscle
      joint unit by means of the analysis of the torque signal recorded during
      electrical stimulation of the tibialis anterior (TA). Ten subjects (age: 23-50
      years, 7 males, 3 females) volunteered for the study. The leg was fixed in an
      ergometer designed for isometric contraction of the ankle dorsiflexors and the
      detection of the generated torque. The amplitude of a 30 Hz stimulation train
      administered at the TA motor point was varied sinusoidally, thus changing the
      number of the recruited motor units, and hence the tension at the tendon, in the
      same fashion. A sequence of 14 frequencies (0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6,
      1.8, 2.0, 2.5, 3.0, 4.0, 5.0, and 6.0 Hz) was administered. RESULTS: (a) at the
      14 frequencies the sinusoidal responses presented distortions always below 2%;
      (b) from the Bode plots reporting the average gain attenuation and phase shift at
      each of the 14 input frequencies, it was possible to model the force dynamic
      response as the one of a critically damped II order system with two real
      coincident poles (at 2.04 Hz) and a pure time delay (15.6 ms). The possibility to
      obtain, by means of the system input-output transfer function, data regarding the
      in vivo mechanics of the muscle-joint unit may represent a novel tool to
      investigate the functional features of different muscle groups. It may be useful
      for designing functional electrical stimulation programs as well as training and
      rehabilitation procedures.

PMID- 16600639
TI  - Automated computation of the Gyrification Index in prefrontal lobes: methods and
      comparison with manual implementation.
AB  - In this paper, we introduce an automated method of calculating Gyrification Index
      (GI), a measure of cortical folding. Automated GI (A-GI) is an in vivo GI
      implementation applied to MRI T1 weighted scans and is designed as an extension
      to the SPM analysis package. The A-GI tool is unbiased in its application, and is
      unlimited in the size of test cohort to which it can be applied. In comparison to
      manual methods, A-GI substantially reduces the time costs and improves
      repeatability. The current A-GI implementation is limited to analysis of
      prefrontal lobes, but an extension to provide whole brain A-GI is under
      consideration. In determination of the GI inner contour, A-GI traces high spatial
      frequencies typically missed in manual tracing, and thus, A-GI reports a high GI
      value. We examine the operation of this tool in two scan cohorts. We establish
      that the tool has good repeatability through its application to a cohort where 5
      well individuals were scanned 5 times over a period of 6 months. This indicates
      that A-GI has low susceptibility to scanner noise and is not affected by the
      variability in brain representation given by repeat scans. We demonstrate
      replication of hand tracing results by comparisons with a manual GI study that
      has shown differences between high risk subjects who go on to develop
      schizophrenia and those who are at high risk but remain well. Direct scan by scan
      comparisons are carried out between manual and A-GI methods. In respect of scan
      orientation and coronal sampling, the methods differ, and these considerations
      contribute to a between methods right prefrontal ICC of 0.67 and left prefrontal
      ICC of 0.63. The replication results demonstrate that A-GI has discriminatory
      power equivalent to manual methods. A-GI is therefore a reliable measure of
      cortical folding that could be usefully applied to a number of MRI data sets of
      the brain in health and disease.

PMID- 16600640
TI  - Functional magnetic resonance imaging characterization of CCK-4-induced panic
      attack and subsequent anticipatory anxiety.
AB  - The main objective of this work was to study the functional markers of the
      clinical response to cholecystokinin tetrapeptide (CCK-4). Twelve healthy male
      subjects were challenged with CCK-4 and simultaneously underwent functional
      magnetic resonance imaging (fMRI) recording. Since anticipatory anxiety (AA) is
      an intrinsic part of panic disorder, a behavioral paradigm, using the threat of
      being administered a second injection of CCK-4, has been developed to investigate
      induced AA. The study was composed of three fMRI scans according to an open
      design. During first and second scan, subjects were injected with placebo and CCK
      4, respectively. The third scan was the AA challenge. CCK-4 administration
      induced physiological and psychological symptoms of anxiety that met the criteria
      for a panic attack in 8 subjects, as well as cerebral activation in anxiety
      related brain regions. Clinical and physiological response intensity was
      consistent with cerebral activity extent and robustness. fMRI proved more
      sensitive than clinical assessment in evidencing the effects of the AA challenge.
      The latter induced brain activation, different from that obtained on CCK-4 and
      during placebo injection, that was likely related to anxiety. The method applied
      in this study is suitable for the study of anxiety using fMRI.

PMID- 16600641
TI  - Donepezil effects on sources of cortical rhythms in mild Alzheimer's disease:
      Responders vs. Non-Responders.
AB  - Acetylcholinesterase inhibitors (AChEI) such as donepezil act in mild Alzheimer's
      disease (AD) by increasing cholinergic tone. Differences in the clinical response
      in patients who do or do not benefit from therapy may be due to different
      functional features of the central neural systems. We tested this hypothesis
      using cortical electroencephalographic (EEG) rhythmicity. Resting eyes-closed EEG
      data were recorded in 58 mild AD patients (Mini Mental State Examination [MMSE]
      range 17-24) before and approximately 1 year after standard donepezil treatment.
      Based on changes of MMSE scores between baseline and follow-up, 28 patients were
      classified as "Responders" (MMSEvar >or=0) and 30 patients as "Non-Responders"
      (MMSEvar <0). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha
      1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz).
      Cortical EEG sources were studied with low-resolution brain electromagnetic
      tomography (LORETA). Before treatment, posterior sources of delta, alpha 1 and
      alpha 2 frequencies were greater in amplitude in Non-Responders. After treatment,
      a lesser magnitude reduction of occipital and temporal alpha 1 sources
      characterized Responders. These results suggest that Responders and Non
      Responders had different EEG cortical rhythms. Donepezil could act by
      reactivating existing yet functionally silent cortical synapses in Responders,
      restoring temporal and occipital alpha rhythms.

PMID- 16600642
TI  - Magnetic resonance imaging of freely moving objects: prospective real-time motion
      correction using an external optical motion tracking system.
AB  - Subject motion and associated artefacts limit the applicability of MRI and the
      achievable quality of the images acquired. In this paper, a fully integrated
      method for prospective correction of arbitrary rigid body motion employing an
      external motion tracking device is demonstrated for the first time. The position
      of the imaging volume is updated prior to every excitation of the spin system.
      The performance of the available tracking hardware and its connection to the MR
      imager is analyzed in detail. With the introduction of a novel calibration
      procedure the accuracy of motion correction is improved compared to previous
      approaches. Together with the high geometry update rate even freely moving
      objects can be imaged without motion related artefacts. The high performance and
      image quality improvement in case of subject motion are demonstrated for various
      imaging techniques such as gradient and spin echo, as well as echo planar
      imaging.

PMID- 16600644
TI  - Hepatic differentiation of mouse ES cells into BE cells in vitro.
AB  - To date, the hepatic differentiation of embryonic stem (ES) cells into biliary
      epithelial (BE) cells has only been identified in hepatocytes. In this study, an
      attempt was made to induce the differentiation of ES cells to BE cells. In order
      to induce hepatic, and then BE cell differentiation, growth factors such as TGF,
      FGF, HGF and EGF were added to the culture medium supplied to embryonic bodies
      (EBs) that were derived from ES cells. The marker genes and corresponding
      proteins of hepatocytes and BE cells such as AFP, ALB, CK8, CK18, CK7, CK19 and
      GGT, etc. were detected by reverse transcriptase-polymerase chain reaction (RT
      PCR), immunocytochemistry (ICC) and enzymatic histochemistry. Lastly, the ratio
      of BE-like cells to all EBs cells was analyzed and determined by flow cytometry
      (FCM). Hepatocyte and BE cell marker genes and proteins were found to be
      expressed in the cytoplasm of differentiated cells. On day 10 of differentiation,
      many round structures appeared in the EBs culture system and the marker proteins
      of BE cells were found to be expressed in these structures. The BE cell
      differentiation ratio continually increased from its initial value of 1.7% on day
      13 to 7.4% on day 21. ES cells were found to be able to differentiate into BE
      cells when cultured using medium with appropriate cell growth factors. These BE
      cells may be a novel source of differentiated cell types for liver engineering.

PMID- 16600643
TI  - Expression and cellular localization of human hyaluronidase-2 in articular
      chondrocytes and cultured cell lines.
AB  - OBJECTIVE: There is debate whether hyaluronan (HA) can be enzymatically degraded
      within the extracellular matrix of cartilage and other tissues or whether its
      catabolism occurs strictly within the lysosomal compartment of chondrocytes and
      other cell types. Previous studies have suggested that one of the lysosomal
      hyaluronidases (hyaluronidase-2) can be expressed as a functionally-active
      glycosyl phosphatidylinositol-linked protein at the surface of mammalian cells.
      If this form of hyaluronidase expression occurs in chondrocytes, this could
      represent a possible mechanism for extracellular HA cleavage. Thus, which
      hyaluronidases are expressed and where was the objective of this study. METHODS:
      mRNA for hyaluronidases was quantified by reverse transcription-polymerase chain
      reaction (RT-PCR) and enzymatic activity by HA zymograms. Recombinant forms of
      hyaluronidase-2 were generated and expressed in model cell lines. A peptide
      specific polyclonal antiserum was prepared to localize endogenous human
      hyaluronidase-2 in human articular chondrocytes. RESULTS: Hyaluronidase-2 is the
      principal mRNA transcript expressed by primary human articular chondrocytes as
      well as various model cell lines. Recombinant hyaluronidase-2, containing N
      terminal or C-terminal epitope tags, was strictly localized intracellularly and
      not released by treatment with a phosphatidylinositol-specific phospholipase.
      Endogenous hyaluronidase-2 expressed by human chondrocytes as well as HeLa cells
      could only be detected following detergent permeabilization of the plasma
      membranes. CONCLUSIONS: These data suggest that on chondrocytes and other cell
      types examined, hyaluronidase-2 is not present or functional at the external
      plasma membrane. Thus, local turnover of HA is dependent on receptor-mediated
      endocytosis and delivery to low pH intracellular organelles for its complete
      degradation.

PMID- 16600645
TI  - Cytoplasmic channels and their association with plastids in male meiocytes of
      tobacco, onion and lily.
AB  - The ultrastructures of male meiocytes in tobacco, onion and lily were studied to
      elucidate the interaction between cytoplasmic channels (CCs) and plastids. Before
      meiosis, the male sporogenous cells had identically thickened cell walls (CWs)
      traversed by typical plasmodesmata (PDs). After entering meiosis, their CWs
      became uneven in thickness and 80-500nm aperture CCs were formed. Simultaneously,
      plastids or plastid-like bodies (PLBs) differing in size and morphology assembled
      at one or both ends of the CCs. These plastids and PLBs commonly orientated their
      sharper ends to face the CCs and were co-orientated on the axial line crossing
      the CC. Such pairs of plastids were often interconnected through the CC by thin
      (50-100nm) threads emanating from their membranes. Sometimes, plastids or PLBs
      extended directly from one side of a CW to the other, forming a bridge via the
      CC. In some cases, several plastids formed bridges between cells via one common
      CC. This is the first report that clearly demonstrates an intercellular continuum
      of, or communication between, plastids in male plant meiocytes.

PMID- 16600646
TI  - Equine eosinophils -- why do they migrate?

PMID- 16600647
TI  - Doppler echocardiographic assessment of the effects of inhaled long-acting beta2
      agonists on pulmonary artery pressure in COPD patients.
AB  - Increase in pulmonary artery pressure (PAP), which is common in severe chronic
      obstructive pulmonary disease (COPD), is a predictor of mortality independent of
      airflow limitation. beta-agonists might slightly attenuate this increase because
      they exert a vasodilating effect on pulmonary circulation when systematically
      administered. We have investigated the acute effects of salmeterol and formoterol
      on echocardiographic systolic pulmonary artery pressure (sPAP) in 20 patients
      with COPD and a sPAP greater than 20mmHg at rest. Acute haemodynamic responses to
      inhaled formoterol or salmeterol were assessed in all patients, in a randomized,
      double-blind double-dummy fashion. On two consecutive days, patients received, in
      a randomized order, formoterol 12microg via Turbuhaler plus placebo via Diskus or
      salmeterol 50microg via Diskus plus placebo via Turbuhaler. Transthoracic Doppler
      echocardiography measurements of sPAP were made before and 15, 30, 60 and 180min
      after bronchodilator inhalation. Lung function, pulse oximetry and heart rate
      were also monitored at the same times. Mean sPAP significantly (p<0.05) decreased
      in comparison with baseline at 15, 30, and 60min post inhalation but returned
      towards control levels at 180min after both salmeterol and formoterol. There was
      no correlation between the maximum increase in FEV(1) and maximum decrease in
      sPAP either after inhalation of salmeterol (r(2)=0.071) or after that of
      formoterol (r(2)=0.0006). The increases in FEV(1) in comparison with baseline
      were always significant (p<0.05) from 15 to 180min post inhalation after either
      salmeterol or formoterol. Neither pulse oximetry nor heart rate changed in a
      significant manner (p>0.05). This study demonstrated that salmeterol and
      formoterol were equally beneficial for pulmonary haemodynamics in patients with
      COPD. A direct vasodilatation due to the activation of beta-adrenoceptors that
      are present in pulmonary vessels is a likely mechanism of their action in
      inducing the decrease in sPAP.

PMID- 16600648
TI  - Temperature dependence of water loss rates in scorpions and its effect on the
      distribution of Buthotus judaicus (Buthidae) in Israel.
AB  - Scorpions of the family Buthidae have been shown to be more desiccation resistant
      in comparison with sympatric Scorpionidae species. This has been attributed to
      the surface-dwelling existence of the former, which unlike most other scorpion
      species do not avoid environmental extremes by burrowing. Still, within Buthidae,
      the mesic Buthotus judaicus showed better osmoregulatory capacities than the
      xeric Leiurus quinquestriatus, largely as a result of its high resistance to
      water loss. However, B. judaicus exhibited poor ability to regulate its
      haemolymph osmolarity at 37 degrees C. In this study we report a sharp increase
      in water loss rates of B. judaicus at the 30-35 degrees C temperature range
      compared to that measured for L. quinquestriatus, which could explain the poor
      osmoregulatory performance of the former at higher ambient temperatures. The
      increase in water loss rates of B. judaicus at high temperatures is not coupled
      with a similar increase in respiratory rate, suggesting an increase in cuticular
      permeability. We suggest that this increase in cuticular permeability, which may
      result from a relatively low critical transition temperature, contributes to
      limiting the distribution of B. judaicus to habitats of moderate environmental
      conditions.

PMID- 16600649
TI  - Effect of nutrient restriction on the somatotropes and substance P-immunoreactive
      cells in the pituitary of the female ovine fetus.
AB  - The maternal environment affects fetal development and may influence the
      physiology of the adult. Fetal growth hormone (GH) is increased by maternal
      undernutrition but the mechanisms responsible are unknown. This study determined
      the effect of maternal undernutrition on the development of fetal pituitary
      somatotropes in the female. Ewes were grouped randomly into control (fed 100% of
      requirements) or nutrient restricted (fed 50%) from Days 28 to 78 of gestation.
      At Day 78, the ewes were killed and fetuses collected (Day 78 NR (nutrient
      restricted): n=6; Day 78C (control): n=6). Remaining ewes were realimented to
      100% of nutritional requirements and were killed at Day 135 (Day 135 NR (nutrient
      restricted): n=6; Day 135 C (control): n=6). Somatotropes were visualized
      immunocytochemically and the size, mean density, total percentage and proportion
      colocalized with substance P were determined for each group. Nutrient restriction
      increased (p<0.01) the density of pituitary cells in Day 78 fetuses but this
      difference was no longer apparent by Day 135 after realimentation. The density
      and proportion of somatotropes were not different between treatment groups at Day
      78 but were significantly (p<0.05) lower in the nutrient restricted Day 135
      fetuses as compared to the Day 135 control animals. Somatotropes from restricted
      fetuses were significantly (p<0.001) larger at Day 78. Nutrient restriction
      increased the density (p<0.001) and percentage (p<0.05) of substance P
      immunoreactive cells Day 135 fetuses. Similarly, the proportion of somatotropes
      that expressed substance P was significantly (p<0.05) increased by nutrient
      restriction in the Day 135 fetuses. Although nearly two thirds of substance P
      immunoreactive cells co-expressed GH, there was no significant effect of
      treatment on this co-expression. Additional studies are required to determine if
      other components of the neuroendocrine GH axis are affected by this nutritional
      insult, if the alterations that we have observed, particularly in the tachykinin
      system, persist into adulthood and, importantly, what are the long-term
      consequences of an altered GH axis.

PMID- 16600650
TI  - A spectrum of molecular variation in a cohort of Italian families with
      trimethylaminuria: identification of three novel mutations of the FM03 gene.
AB  - Fish-odor syndrome or trimethylaminuria, is a rare inborn error of metabolism
      inherited in an autosomal recessive fashion, involving the dysfunction of hepatic
      enzyme flavin-containing monooxygenase 3 (FMO3) that converts fishy-smelling
      trimethylamine (TMA) into odorless trimethylamine-N-oxide (TMAO). This confers,
      to the affected individual a very unpleasant body odor resembling that of rotting
      fish. This disorder has been relatively well-documented in British, Australian,
      and American populations and reports have appeared regarding patients in Thailand
      and Hong Kong, but no Italian families affected by trimethylaminuria have been
      reported in the literature. We have collected a cohort of Italian families and
      investigated the genetic basis of the disorder in these Italian pedigrees
      disclosing a spectrum of molecular variation in the FM03 gene comprising three
      novel deleterious mutations: the first documented de novo missense mutation
      causative of trimethylaminuria; a guanidine nucleotide deletion (G1182del) at
      codon 394 and a novel missense mutation (R238P) that altered highly conserved
      amino acid in the exon 6. Moreover, we investigated by aplotype analysis a family
      with mild TMAuria identifying a putative causative aplotype. Finally, we failed
      to detect any variation in other Italian families suggesting that this gene is
      not associated with all clinical form of trimethylaminuria or that polymorphisms
      in this gene could be susceptibility factors for developing the disease. Our
      findings support the hypothesis that TMAuria is not a rare recessive disorder but
      rather a spectrum of malodour phenotypes in which diet and environmental
      exposures can play a role in triggering symptoms.

PMID- 16600651
TI  - Newborn screening for lysosomal storage disorders.
AB  - Lysosomal storage disorders (LSD) are chronic progressive diseases that have a
      devastating impact on the patient and family. Most patients are clinically normal
      at birth but develop symptoms early in childhood. Despite no curative treatment,
      a number of therapeutic options are available to improve quality of life. To
      achieve this, there is a pressing need for newborn screening to identify affected
      individuals early, before the onset of severe irreversible pathology. We have
      developed a multiplexed immune-quantification assay of 11 different lysosomal
      proteins for the identification of individuals with an LSD and evaluated this
      assay in a retrospective study using blood-spots from; newborns subsequently
      diagnosed with an LSD (n=19, six different LSD), individuals sampled after
      diagnosis of an LSD (n=92, 11 different LSD), newborn controls (n=433), and adult
      controls (n=200). All patients with mucopolysaccharidosis type I (MPS I), MPS II,
      MPS IIIA, MPS VI, metachromatic leukodystrophy, Niemann-Pick disease type A/B,
      and multiple sulfatase deficiency could be identified by reduced enzyme levels
      compared to controls. All mucolipidosis type II/III patients were identified by
      the elevation of several lysosomal enzymes, above the control range. Most Fabry,
      Pompe, and Gaucher disease patients were identified from either single protein
      differences or profiles of multiple protein markers. Newborn screening for
      multiple LSD is achievable using multiplexed immune-quantification of a panel of
      lysosomal proteins. With further validation, this method could be readily
      incorporated into existing screening laboratories and will have a substantial
      impact on patient management and counseling of families.

PMID- 16600652
TI  - Immunoglobulin concentrations in feline colostrum and milk, and the requirement
      of colostrum for passive transfer of immunity to neonatal kittens.
AB  - The purpose of this study was to clarify whether cats have a colostral and milk
      phase of lactation differentiated by concentrations of immunoglobulins, and
      whether colostrum ingestion by newborn kittens is essential for optimal transfer
      of passive immunity. Milk from specific pathogen-free queens was analyzed for IgG
      and IgA concentrations from parturition through 6 weeks of lactation. Serum IgG
      and IgA concentrations from birth through 8 weeks of age were determined for
      colostrum-fed kittens, colostrum-deprived kittens that were fed a milk replacer,
      and colostrum-deprived kittens that were fostered onto queens in the milk phase
      of lactation. The total IgG and IgA concentrations in milk were significantly
      higher on the day of parturition than on day 7 of lactation, indicating cats do
      have a colostral phase of lactation. The predominant immunoglobulin in both
      colostrum and milk was IgG. The serum IgG concentrations in colostrum-deprived
      kittens fostered on queens in the milk phase of lactation were similar to
      colostrum-deprived kittens fed a milk replacer, and the concentrations were
      significantly lower than in colostrum-fed kittens for the first 4 weeks of life.
      The serum IgA concentrations in both colostrum-deprived groups were significantly
      lower than colostrum-fed kittens on day 2 after parturition, but were similar
      thereafter. Colostrum-deprived kittens fostered onto queens in the milk phase of
      lactation had failure of passive transfer of maternal antibodies. Protective
      concentrations of immunoglobulins can be restored in kittens with failure of
      passive transfer of immunity by parenteral administration of adult cat serum, but
      not by fostering on queens in mid-lactation.

PMID- 16600653
TI  - Intracranial neoplasia in 61 cats: localisation, tumour types and seizure
      patterns.
AB  - The purpose of this study was to analyse retrospectively a feline population with
      intracranial neoplastic diseases, to document seizure patterns in these animals
      and to determine whether partial seizures were more frequently associated with
      structural brain lesions then generalised seizures. In addition, a comparison was
      made within the population with intracranial neoplasia between two groups of
      cats: one with and one without seizures. Special emphasis was given to the
      evaluation of tumour type, localisation and size of the lesion and its
      correlation with seizure prevalence. Sixty-one cats with histopathological
      diagnosis of intracranial tumour were identified. Fourteen cats (23%; group A)
      had a history of seizure(s). Forty-seven cats (77%; group B) had no history of
      seizure(s). Generalised tonic-clonic seizures were seen in eight cats (57%) and
      were the most common seizure pattern in our cats with intracranial neoplasia.
      Clusters of seizures were observed in six cats. Status epilepticus was observed
      in one patient. The mean age of the cats was 7.9 years within group A (median
      8.5) and 9.3 years (median 10) within group B. The cats with lymphoma within both
      groups were significantly younger than cats with meningioma. In both groups
      meningioma and lymphoma were confirmed to be the most frequent tumour type,
      followed by glial cell tumours. The prevalence of the seizures in patients with
      glial cell tumours was 26.7%, 26.3% in patients with lymphomas and 15% in cases
      with meningiomas. In 33 cases (54.1%) the tumours were localised in the
      forebrain, 15 tumours (24.6%) were in the brainstem, four (6.6%) in the
      cerebellum and nine tumours (14.7%) had multifocal localisation. Parietal lobe
      and basal ganglia mostly affected group A. In group B tumours were most
      frequently located in the parietal and frontal lobes as well as in the
      diencephalon. A positive association was documented between the localisation of a
      tumour in the forebrain and seizure occurrence.

PMID- 16600654
TI  - Surgical approach for tentorial meningiomas in cats: a review of six cases.
AB  - The surgical technique for removal of tentorial meningiomas is described on six
      cats using a unilateral temporal supracerebellar transtentorial approach.
      Complete gross tumour resection was achieved in four of six cats. In one cat,
      only subtotal resection was achieved. One cat died shortly after surgery because
      of extensive cerebral haemorrhage. The surgical approach, combined with cisternal
      or ventricular cerebrospinal fluid puncture and an open-window technique (tumour
      fenestration and enucleation) provided sufficient visibility and tumour
      accessibility without excessive manipulation of the brain parenchyma. In all
      patients, a postoperative transient worsening of the clinical signs was observed.
      The neurological signs resolved with time with the exception of blindness in two
      cats. All five surviving cats were monitored for a mean follow-up time of 19
      months (median 20 months; range 6-30 months). All patients died or were
      euthanased because of tumour regrowth within the follow-up period. Although
      challenging, surgical treatment is a useful therapeutic measure in the treatment
      of cats presenting with tentorial meningiomas.

PMID- 16600655
TI  - The lack of Crimean-Congo hemorrhagic fever virus antibodies in healthcare
      workers in an endemic region.
AB  - We aimed to detect antibodies against Crimean-Congo hemorrhagic fever virus
      (CCHFV) in healthcare workers (HCWs) in an endemic region. The study was
      conducted in a tertiary care hospital that had cared for CCHFV infected patients
      in the period 2002-2003. The sera from the HCWs were collected one month after
      the last admitted hospital case (October 2003), and sent to the Pasteur
      Institute, Lyon, France to be studied for CCHF IgM and IgG by ELISA. The total
      number of HCWs included in the study was 75; the median age was 30, 68% of the
      subjects were female, and 83% of the HCWs were at risk of exposure to the body
      fluids of patients. Only one HCW from the group without risk of exposure was CCHF
      IgG positive. The adherence rate to universal precautions was high. In
      conclusion, a lack of CCHFV transmission from patients to HCWs was observed. This
      result could be related to the high rate of compliance to the universal
      precautions, which are sufficient to protect against CCHFV infection.

PMID- 16600656
TI  - Human leptospirosis in Portugal: A retrospective study of eighteen years.
AB  - INTRODUCTION: Leptospirosis, an under-recognized public health problem, needs to
      be confirmed through specific laboratory diagnosis. DESIGN: We describe herein a
      series of 4618 symptomatic patients for whom a microagglutination test (MAT)
      serology was available, representing a unique picture of human leptospirosis in
      central mainland Portugal and the Azores islands of Sao Miguel and Terceira, over
      eighteen- and twelve-year periods, respectively. RESULTS: The distribution of the
      1024 (22%) cases identified was an average 57 cases per year, with higher
      frequency in males (67%). These represent the majority of leptospirosis
      notifications in Portugal, with a higher annual incidence rate in the islands,
      compared to the central mainland (11.1 and 1.7/100,000 population, respectively).
      Middle-aged adults (25-54 years) were most frequently infected (45%). Cases
      occurred mainly in December and January. Serovars from nine presumptive
      serogroups caused infection, with a predominance of Icterohaemorrhagiae, Pomona,
      and Ballum, accounting for 66% of cases. CONCLUSIONS: Seropositivity was
      associated with both anicteric and icteric leptospirosis. Several risk factors
      and a higher transmission risk in certain areas were emphasized. Leptospirosis
      was confirmed as a steadily increasing public health problem; good surveillance,
      communication, and laboratory support are thus necessary to reduce the impact of
      leptospirosis in areas at risk.

PMID- 16600657
TI  - [Evaluation of the 22nd Congress of the SFTS (French Society of Blood
      Transfusion), 28-30 June 2005, Palais-du-Grand-large (Saint-Malo)].

PMID- 16600658
TI  - [Formation-information].

PMID- 16600659
TI  - [Medulloblastoma with extracentral nervous system metastases: clinical
      presentation and risk factors].
AB  - PURPOSE: Extra-central nervous system (extra-CNS) metastases are relatively
      unknown failure patterns in medulloblastoma. The aim of this study was to analyse
      epidemiological, clinical and aetiopathological aspects of these extra-CNS
      localisations. PATIENTS AND METHODS: Extra-CNS metastases were retrospectively
      identified in patients treated in the department of radiation therapy at Salah
      Azaiz institute (ISA) for medulloblastoma. These metastases were diagnosed as
      extra-CNS for all secondary localisations not related to other tumour aetiology.
      Aetiopathological aspects are discussed with a literature review. RESULTS: Among
      103 patients treated and followed-up in the department of radiation therapy of
      ISA from 1970 to 1992, 8 developed extra-CNS metastases (7.7%). Age at diagnosis
      of primitive tumour varied from 3 to 23 years. Sex ratio was 1. Primitive tumour
      treatment was: complete surgical resection in 4 patients with preoperative
      cerebrospinal fluid shunting in two, cerebrospinal axis irradiation in 7 patients
      and a cerebral-limited irradiation in 1. Two patients received chemotherapy for
      their initial treatment (systemic in one case and intrathecal in the other). The
      mean free-interval from diagnosis of primitive tumour to extra-CNS metastases was
      23 months, varying from 8 to 53 months. These metastases were located in the
      liver (1 case), cervical lymph nodes (2 cases), bone marrow (1 case) and bone (2
      cases). Two patients had multiple metastases: bone and bone marrow (in one),
      lung, pleura, cervical lymph node and bone localisations (in one). Treatment of
      these metastases was: chemotherapy in 5 cases, chemotherapy and radiation in one,
      radiation therapy in one and 2 patients were given only supportive care
      treatment. All patients died or are in progressive disease in less than one year
      from the diagnosis of extra-CNS metastases. CONCLUSION: Extra-CNS metastases are
      not rare and have a poor prognosis. The most commonly involved sites are bone,
      cervical lymph nodes and bone marrow. A complete work-up at initial diagnosis is
      recommended to screen early metastases. Literature review showed that
      histopathologic grading might help to identify groups at risk.

PMID- 16600660
TI  - [Words and acts].

PMID- 16600661
TI  - [Use of prosthetic materials in reconstructive pelvic floor surgery. An evidence
      based analysis].
AB  - Many surgical procedures for the repair of pelvic organ prolapse are used
      nowadays. Reconstructive pelvic surgery continues to evolve while surgeons
      continue to search the definitive surgical cure and have to choose the most
      appropriate procedures for their patients. Concerning the vaginal approach
      procedures, there is an increasing interest in the use of synthetic meshes which
      are at present widely used for surgical repair of pelvic organ prolapse.
      Prosthetic repair seems to be more reliable, especially when native tissues are
      of poor quality. The use of synthetic meshes may also simplify surgical
      procedures and reduce operative duration and morbidity. Material must be inert,
      permanent and resistant to infection. Based on authors' and other researchers'
      published experimental and clinical experience, polypropylene is assumed to be
      the most appropriate material for the vaginal repair of pelvic organ prolapse.
      However, since no standardized outcome measure is available, it is difficult to
      compare the results of surgical procedures. Only in recent studies, the
      subjective cure rates (patient satisfaction and outcome) have been assessed as
      well as the objective cure rates determined by the investigators. The subjective
      cure rate is probably more influenced by the functional outcome and sexual
      activity than by the anatomical result. Continuous evaluation is necessary to
      study replacement synthetic materials which should improve the rate of prolapse
      recurrence and reduce the risk of complications. Randomized controlled trials are
      required to determine which surgical procedures and type of prosthesis are most
      suitable. This review evaluates the properties of prosthetic materials, their
      complications and the most common procedures involved in the use of meshes for
      pelvic reconstructive surgery.

PMID- 16600662
TI  - [Comparison of transobturator tape (TOT) and tension-free vaginal tape (TVT)
      using perineal ultrasound].
AB  - OBJECTIVE: Using perineal ultrasound in two groups of patients having either TVT
      or TOT procedure to know if TOT is sufficiently oblique and if the large
      dissection in TOT procedure might be responsible for migration of the tape.
      PATIENTS AND METHODS: Thirty-two patients, 16 TVT and 16 TOT, had a sonography.
      The tape is visualised in the sagittal and frontal planes at rest, maximum
      holding and valsalva straining. The angle between the two limbs of the tape is
      measured as well as the distance tape-bladder neck and the width of the tape.
      RESULTS: The aspect of the tape at rest is like a V, in both groups. During
      straining, the urethra is flattened on the tape which becomes round. During
      maximum retaining, the V closes by traction on the limbs. The mean angle under
      the urethra at rest is 109.9 degrees. In the TVT group it is 101.6 degrees versus
      118.1 degrees in the TOT group. This difference is statistically significant
      (P=0.001). The width of the tape is 6.7 mm (2.4-10.3). The distance tape-bladder
      neck is 14.8 mm (8.2-25.7), 14.6 mm for the TVT group and 15.6 mm for the TOT
      group, the mean urethral length being 33.1 mm. DISCUSSION AND CONCLUSION: The
      angle of TOT is more open. It remains sufficiently oblique and allows the tape to
      be put with light tension if needed in low-pressure urethra. In spite of larger
      urethrovaginal dissection in TOT, the tape does not migrate close to the bladder
      neck and remains at mid-urethra.

PMID- 16600663
TI  - The ARF tumour suppressor.
AB  - The ARF tumour suppressor is a product of the INK4a/ARF locus; a sequence that is
      frequently altered in human cancer. ARF is upregulated by oncogenic stimuli and
      is a critical regulator of p53 stability through interactions with the mdm2 and
      ARF-BP1/Mule ubiquitin ligases. Cellular stress signals liberate ARF from the
      nucleolus where it is bound to B23/nucleophosmin. This nucleolar location of ARF
      may serve as a reservoir for the rapid induction of p53, but may also serve to co
      ordinate effects on cell cycle, survival and growth. The biological functions of
      ARF interactions with other binding partners remain uncertain, but ARF-mediated
      sumoylation may represent a unifying effector pathway.

PMID- 16600664
TI  - Leucine-rich repeat kinase 2: relevance to Parkinson's disease.
AB  - Human leucine-rich repeat kinase 2 (LRRK2) is a novel kinase belonging to the
      ROCO protein superfamily (Ras of complex proteins (Roc) with a C-terminal of Roc
      domain). This large complex protein of 280kDa contains several functional domains
      including leucine-rich repeats, Ras-related GTPase, mitogen-activated protein
      kinase kinase kinase (MAPKKK), and WD40 repeats. While definitive functions of
      LRRK2 have yet to be described, the domain structure of LRRK2 suggests that it
      plays an important role in the regulation of signal transduction cascades through
      its dual enzymatic activities of GTPase and MAPKKK. Moreover, mutations in LRRK2
      have been found to be thus far the most frequent cause of late-onset familial and
      idiopathic Parkinson's disease. Further investigations should allow for the
      elucidation of how pathogenic mutations trigger changes in the structure and
      function of LRRK2 that lead to aberrant signal transduction and neurodegeneration
      in Parkinson's disease.

PMID- 16600665
TI  - M-CSF induces the stable interaction of cFms with alphaVbeta3 integrin in
      osteoclasts.
AB  - The macrophage colony stimulating factor receptor (cFms) and alpha(V)beta(3)
      integrin are both abundantly expressed and play critical roles in the
      differentiation, survival and migration of osteoclasts. We have previously
      demonstrated that cross-talk between cFms- and alpha(V)beta(3)-mediated signaling
      pathways regulated the cytoskeletal organization required for osteoclast
      migration. To investigate the nature of interaction between the two receptors, we
      sequentially used anion-exchange chromatography and immunoprecipitation to purify
      alpha(V)beta(3)-associated protein complexes. We have demonstrated that cFms
      stably associated with alpha(V)beta(3) in osteoclasts during adhesion, and that
      the association was induced by macrophage colony stimulating factor (M-CSF)
      stimulation. However, the kinetics of association of alpha(V)beta(3) and cFms did
      not correlate with the kinetics of tyrosine phosphorylation of cFms. Instead,
      maximally observed alpha(V)beta(3)/cFms association was after the peak of cFms
      tyrosine phosphorylation and correlated inversely with the total amount of cFms
      remaining. Furthermore, the complex containing cFms and alpha(V)beta(3) also
      contained a number of other signaling molecules including Pyk2, p130(Cas) and c
      Cbl, known downstream regulators of the integrin-mediated signaling pathways in
      osteoclasts. In the presence of M-CSF, co-localization of alpha(V)beta(3)
      integrin and cFms was identified in the podosomal actin ring of the osteoclast
      during adhesion on glass. Interestingly, co-localization of both receptors was
      not found in the sealing zone, but in punctate structures associated with
      adhesion- or transcytosis-like structures in osteoclasts on bone. Taken together,
      we suggest that the association of alpha(V)beta(3) and cFms could be the result
      of signaling following tyrosine phosphorylation of cFms. The recruitment of cFms
      to alpha(V)beta(3) integrin may be an integral part of a larger signaling complex
      via which both of adhesion- and growth factor receptors coordinately regulate
      osteoclast adhesion, motility and membrane trafficking.

PMID- 16600666
TI  - Explaining delusions: a cognitive perspective.
AB  - There is now considerable evidence for reasoning, attention, metacognition and
      attribution biases in delusional patients. Recently, these findings have been
      incorporated into a number of cognitive models that aim to explain delusion
      formation, maintenance and content. Although delusions are commonly
      conceptualized as beliefs, not all models make reference to models of normal
      belief formation. This review considers those models that explain delusions as a
      breakdown of normal belief formation (belief-positive models), approaches that
      explain the pathology only (belief-negative models) and approaches that view
      delusions as one end of a distribution of anomalous mental phenomena (the
      continuum view). A cognitive theory that includes the 'pragmatic pathology' of
      delusions will be able to address both the phenomenology and the treatment of
      delusion-related distress.

PMID- 16600667
TI  - The AS biometry technique--a novel technique to aid accurate intraocular lens
      power calculation after corneal laser refractive surgery.
AB  - Intraocular lens power (IOL) calculation for cataract surgery has been shown to
      be inaccurate after photorefractive keratectomy (PRK), laser-assisted
      subepithelial keratectomy (LASEK) and laser in situ keratomileusis (LASIK). Many
      techniques exist to calculate corneal power with varying results and require the
      clinician to be aware of the pitfalls of IOL power calculation in post-refractive
      eyes. The AS biometry method proposed here is a simple method which does not rely
      on the calculation of corneal power. This new method is compared to the current
      gold standard the clinical history method (CHM). Twenty-nine eyes of 15 patients
      had routine biometry prior to LASIK, LASEK or PRK. The range of pre-operative
      spherical equivalent refractive error was -5.37 to +4.00 diopters. The post
      operative refraction was measured at 3-6 months. The IOL power calculation was
      calculated using the AS biometry method and the CHM. The two methods were
      compared using the Student's paired t-test and the Bland Altman technique. There
      was no statistical difference between the AS biometry method and the CHM. The
      paired Student's t-test comparing the AS biometry method and the CHM showed no
      statistical difference, t=0.33 with a p-value of 0.75, at a 95% confidence
      interval. The authors conclude that the AS biometry technique is as accurate as
      the CHM. The former is a simpler method which avoids many of the pitfalls and
      confounding factors involved in IOL power calculation following corneal excimer
      laser surgery. However, like the CHM it requires measurements prior to laser
      surgery.

PMID- 16600668
TI  - Restoring p53-mediated apoptosis in cancer cells: new opportunities for cancer
      therapy.
AB  - The p53 gene is the most commonly mutated gene known in human tumors; over half
      of human tumors contain inactivating mutations in p53. In the past decade, the
      role of p53 as apoptotic trigger has been well demonstrated both in vitro and in
      vivo. Many chemotherapeutic agents cause DNA damage and activate the p53 pathway
      to induce growth arrest and apoptosis. However, the p53 function is often
      inactivated or suppressed in human cancers. Thus, functional restoration of this
      pathway is an attractive therapeutic strategy. In recent years, a number of
      therapeutic approaches aiming at modulation of the p53 pathway have been
      developed and will be reviewed here. The focus will be on recent developments
      elucidating a transcription-independent mechanism of p53-mediated apoptosis and
      the therapeutic opportunities arising from this new mechanism.

PMID- 16600669
TI  - Variations on a theme: synthesis and modification of plant benzoic acids.
AB  - Plant benzoic acids (BAs) are critical regulators of a plant's interaction with
      its environment. In addition, innumerable plant-derived pharmacological agents
      contain benzoyl moieties. Despite the prevalence and import of plant BAs, their
      biosynthetic pathways are not well-defined. Mounting evidence suggests that BAs
      are synthesized both directly from shikimate/chorismate and from phenylalanine in
      plants; however, few genes in these pathways have been identified. Exciting
      progress has been made in elucidating genes that modify BAs via methylation,
      glucosylation, or activation with Coenzyme A. As these modifications alter the
      stability, solubility, and activity of the BAs, they impact the functional roles
      of these molecules. The combination of multiple BA biosynthetic routes with a
      variety of chemical modifications probably facilitates precise temporal and
      spatial control over active forms, as well as the channeling of intermediates to
      particular benzoate products.

PMID- 16600670
TI  - Terpene synthases and the regulation, diversity and biological roles of terpene
      metabolism.
AB  - Terpene synthases are the primary enzymes in the formation of low-molecular
      weight terpene metabolites. Rapid progress in the biochemical and molecular
      analysis of terpene synthases has allowed significant investigations of their
      evolution, structural and mechanistic properties, and regulation. The
      organization of terpene synthases in large gene families, their characteristic
      ability to form multiple products, and their spatial and temporal regulation
      during development and in response to biotic and abiotic factors contribute to
      the time-variable formation of a diverse group of terpene metabolites. The
      structural diversity and complexity of terpenes generates an enormous potential
      for mediating plant-environment interactions. Engineering the activities of
      terpene synthases provides opportunities for detailed functional evaluations of
      terpene metabolites in planta.

PMID- 16600671
TI  - A generic concept for the implementation of medical image retrieval systems.
AB  - This paper presents a technical framework to support the development and
      installation of system for content-based image retrieval in medical applications
      (IRMA). A strict separation of feature extraction, feature storage, feature
      comparison, and the user interfaces is suggested. This allows to reuse
      implemented components in different retrieval algorithms, which improves software
      quality, shortens the development cycle for applications, and allows to introduce
      standardized end-user interfaces. Based on the proposed framework, the IRMA
      engine has been established, which is currently used to evaluate content-based
      retrieval methods on a collection of 20,000 medical and 135,000 non-medical
      images.

PMID- 16600672
TI  - The influence of marginal zinc deficient diet on post-vaccination immune response
      against hepatitis B in rats.
AB  - AIM: To evaluate in vitro T lymphocyte proliferation and specific antibody
      response to hepatitis B vaccination in two groups of rats fed with normal and
      marginal zinc content. METHODS: Twenty-two Wistar-Albino rats were randomly
      assigned into two groups and were fed with constant diet. Zinc was suplemented
      10mg/kg dry weight in group I (marginal zinc content) (n=14) and 30mg/kg dry
      weight in group II (n=8). Hepatitis B vaccine (Engerix B, 4mug) was administered
      intramuscularly after 8 weeks on feeding and a booster dose was applied 4 weeks
      after the first injection. Rats were killed 3 weeks after the second injection.
      Peripheral blood mononuclear cells were stimulated in vitro by PHA (2.5mug/ml)
      and hepatitis B surface antigen (2.5, 5, 10mug/ml). Proliferation was evaluated
      by ELISA (celltiter-96 aqueous one solution cell proliferation assay). Serum
      zinc, anti-HBs titer and zinc per dry liver weight were also measured. Two groups
      were compared with respect to antigen specific antibody and lymphocyte
      proliferation responses. Proliferation response to HbsAg were expressed as net
      percent increase (pci) in lymphocyte proliferation from the baseline activity.
      RESULTS: Rats' mean body weight and weight gain per month were similar. Median
      serum zinc was 39 (23-75) and 76(64-115)mug/dl of groups I and II rats,
      respectively (p<0.05), while there was no difference in liver zinc content
      between the two groups (37mug/g dry weight versus 32mug/g dry weight). Median
      anti-HBs levels of groups I and II were 741 (0-10,000)IU/l, 5791 (558
      10,000)IU/l, respectively (p<0.05). In lymphocyte proliferation assays, mean net
      pci with HbsAg of 5 and 10mug/ml were 9.4% and 11.3% in group I rats; while they
      were 25.3% and 26.1% in group II rats (p<0.01 and p<0.01, respectively).
      CONCLUSION: In vitro cell-mediated immune response and in vivo specific antibody
      response to hepatitis B vaccine was decreased in rats fed a diet with marginal
      zinc content. These observations have shown that marginal Zn deficiency might
      influence the efficacy of hepatitis B vaccination in humans.

PMID- 16600673
TI  - Distribution of cholesterol and galactosylceramide in rat cerebellar white
      matter.
AB  - White matter and the inner granular layer of rat cerebellum was analysed by
      imaging time-of-flight secondary-ion mass spectrometry (TOF-SIMS) equipped with a
      Bi+ ion cluster gun. Samples were prepared by high pressure freezing, freeze
      fracturing and freeze drying or by plunge freezing and cryostat sectioning. The
      identified and localized chemical species were: sodium, potassium,
      phosphocholine, cholesterol and galactosylceramide (GalC) with carbon chain
      lengths C18:0 (N-stearoyl-galactosylceramide) and C24:0 (N
      lignoceroylgalactosylceramide) with CH24:0 (hydroxy
      lignoceroylgalactosylceramide). We report new findings regarding the organization
      of myelin in white matter. One is cholesterol-rich, ribbon-shaped 10-20 microm
      areas excluding Na+ and K+. The second finding is the different distribution of
      GalC C18 and GalC C24 in relation to these areas, where GalC C18 was localized in
      cholesterol-rich areas and GalC C24 was localized in Na/K-enriched areas. The
      distribution of GalC was in small spots, homogeneous in size, of 0.8-1.5 microm.
      Sample preparation with high pressure freezing allowed separate localization of
      sodium and potassium in tissue samples.

PMID- 16600674
TI  - Segmental study of the median nerve versus comparative tests in the diagnosis of
      mild carpal tunnel syndrome.
AB  - OBJECTIVE: The aims of this study were to analyze normative data of nerve
      conduction studies (NCS) by optimal transformations, and compare the utility of
      electrodiagnostic tests in detecting mild carpal tunnel syndrome (CTS). METHODS:
      In 131 hands of patients with mild CTS and 136 hands of controls, the segmental
      study of the median nerve between the digit-palm and palm-wrist segments, and the
      median-to-ulnar and median-to-radial comparative tests were performed. Normal
      limits were derived by calculating the mean+/-2 standard deviations of the
      optimally transformed data of the controls. The specificity, sensitivity, and
      misclassification rate were calculated to evaluate the utility of each test.
      RESULTS: All tests had high specificities, ranging from 98.5 to 100%. The
      distoproximal latency ratio (DPLR) of the median nerve showed the highest
      sensitivity and the difference between the median and radial sensory latencies
      (D1M-D1R) the second highest, but there was no statistical difference between
      them. The difference between the median and ulnar mixed nerve latencies in the
      palm-to-wrist segment (PM-PU) showed the lowest sensitivity. Misclassification
      rates of the DPLR, D1M-D1R, and PM-PU were 6.9, 3.8, and 6.1%, respectively.
      CONCLUSIONS: Optimal transformation of NCS data is mandatory to diminish the
      effect of skewness and enhance the diagnostic accuracy. As compared to the
      comparative tests, the segmental study of the median nerve is more easily applied
      and yields higher sensitivity in detecting mild CTS. SIGNIFICANCE: With a high
      diagnostic yield and easy application, the segmental study of the median nerve
      may routinely be used to evaluate patients with mild CTS.

PMID- 16600675
TI  - Frequency and severity of carpal tunnel syndrome according to level of cervical
      radiculopathy: double crush syndrome?
AB  - OBJECTIVE: The double crush hypothesis (DC) proposes that a proximal lesion along
      an axon predisposes it to injury at a more distal site along its course through
      impaired axoplasmic flow. The frequency and severity of carpal tunnel syndrome
      (CTS) according to the level of cervical radiculopathy were investigated to
      evaluate the hypothesis of DC. METHODS: The frequency of CTS was investigated in
      277 patients with C6, C7 or C8 radiculopathies and correlation between CTS and
      radiculopathy level was determined. We also investigated whether the degrees of
      abnormal sensory responses were more severe in C6, C7 radiculopathies and whether
      motor responses were more severe in C8 radiculopathy. RESULTS: Thirty-nine
      patients were diagnosed with CTS and concomitant cervical radiculopathy at the
      C6, 7, or C8 root levels. The frequency of coexisting CTS was not statistically
      different according to the level of radiculopathy. The electrophysiologic results
      revealed no significant correlation between median sensory parameters and C6, C7
      cases, and no relationship was observed between median motor responses and C8
      radiculopathy. CONCLUSIONS: The frequency and electrophysiologic data of CTS
      analyzed according to cervical radiculopathy level do not support a
      neurophysiological explanation. SIGNIFICANCE: Based on this study, the DC
      hypothesis could not be supported.

PMID- 16600676
TI  - Algorithm architectures for patient dependent seizure detection.
AB  - OBJECTIVE: The goal of this work is to determine whether improved performance
      (compared to patient independent algorithms) can be achieved by an algorithm,
      developed on the fly, that requires no user input beyond the identification of
      the first one or two seizures in the record. METHODS: The previously developed
      AutoLearn algorithm, which employs the probabilistic neural network (PNN), is
      tested on 209 seizures obtained from the epilepsy monitoring unit (EMU) or
      ambulatory recordings. A construction algorithm is used to compare a variety of
      algorithm architectures and factors. The Taguchi design of experiments (DoE)
      method is employed find the significant factors without resorting to a full
      factorial design. RESULTS: Architectures that train a single PNN per channel and
      use segmentation to identify ranges of similar activity are preferred. The two
      best architectures are insensitive to the levels of any of the other factors
      tested. The training time for the algorithm is less than 1s, and approximately 2
      min are required to find the seizures in an 8 h record. CONCLUSIONS: The final
      algorithm, which requires no input from the user other than the marking of the
      first seizure in a record, performs as well or better than the 3 seizure
      detectors on EMU and ambulatory records. The algorithm performs nearly as well as
      human experts on the EMU records. SIGNIFICANCE: The described method can be used
      to identify unusual seizures (or other patterns) that will be missed by the
      current generation of seizure detectors. We expect that the methods developed
      here will also aid the development of patient independent seizure detectors that
      can improve their performance over time by incorporating new examples.

PMID- 16600678
TI  - Transient motor evoked potential suppression following a complex sensorimotor
      task.
AB  - OBJECTIVE: To investigate the mechanism involved in the transient suppression of
      the response to transcranial magnetic stimulation (TMS) following repeated
      performance of a complex sensorimotor training task (ST). METHODS: A total of 19
      healthy subjects participated in 4 experiments, all involving performance of the
      grooved pegboard test (GPT). The experiments investigated the effect of the ST on
      corticospinal and intracortical excitability, spinal excitability and maximal
      pinch grip force. RESULTS: Motor evoked potential amplitude decreased
      significantly following the ST in both muscles tested and this was associated,
      but not correlated, with a decrease in the time taken to perform the GPT. There
      was no change in intracortical inhibition or facilitation (tested at
      interstimulus intervals of 3 and 10 ms, respectively). M wave amplitude was
      unchanged, as were F wave amplitude, latency and persistence and there was no
      evidence of muscle fatigue. CONCLUSIONS: The reduction in corticospinal
      excitability was short lasting (<10 min) and was not accompanied by changes at
      the spinal or peripheral level, suggesting that other intracortical circuits may
      be involved. SIGNIFICANCE: Repeated performance of motor tasks can result in both
      short- and long-term modulation of motor cortical excitability. However, the
      relationship between changes in corticospinal excitability and motor performance
      is complex and critically dependent upon task type and duration.

PMID- 16600679
TI  - GIS, geostatistics, metadata banking, and tree-based models for data analysis and
      mapping in environmental monitoring and epidemiology.
AB  - By the example of environmental monitoring, some applications of geographic
      information systems (GIS), geostatistics, metadata banking, and Classification
      and Regression Trees (CART) are presented. These tools are recommended for
      mapping statistically estimated hot spots of vectors and pathogens. GIS were
      introduced as tools for spatially modelling the real world. The modelling can be
      done by mapping objects according to the spatial information content of data.
      Additionally, this can be supported by geostatistical and multivariate
      statistical modelling. This is demonstrated by the example of modelling marine
      habitats of benthic communities and of terrestrial ecoregions. Such
      ecoregionalisations may be used to predict phenomena based on the statistical
      relation between measurements of an interesting phenomenon such as, e.g., the
      incidence of medically relevant species and correlated characteristics of the
      ecoregions. The combination of meteorological data and data on plant phenology
      can enhance the spatial resolution of the information on climate change. To this
      end, meteorological and phenological data have to be correlated. To enable this,
      both data sets which are from disparate monitoring networks have to be spatially
      connected by means of geostatistical estimation. This is demonstrated by the
      example of transformation of site-specific data on plant phenology into surface
      data. The analysis allows for spatial comparison of the phenology during the two
      periods 1961-1990 and 1991-2002 covering whole Germany. The changes in both plant
      phenology and air temperature were proved to be statistically significant. Thus,
      they can be combined by GIS overlay technique to enhance the spatial resolution
      of the information on the climate change and use them for the prediction of
      vector incidences at the regional scale. The localisation of such risk hot spots
      can be done by geometrically merging surface data on promoting factors. This is
      demonstrated by the example of the transfer of heavy metals through soils. The
      predicted hot spots of heavy metal transfer can be validated empirically by
      measurement data which can be inquired by a metadata base linked with a
      geographic information system. A corresponding strategy for the detection of
      vector hot spots in medical epidemiology is recommended. Data on incidences and
      habitats of the Anophelinae in the marsh regions of Lower Saxony (Germany) were
      used to calculate a habitat model by CART, which together with climate data and
      data on ecoregions can be further used for the prediction of habitats of
      medically relevant vector species. In the future, this approach should be
      supported by an internet-based information system consisting of three components:
      metadata questionnaire, metadata base, and GIS to link metadata, surface data,
      and measurement data on incidences and habitats of medically relevant species and
      related data on climate, phenology, and ecoregional characteristic conditions.

PMID- 16600680
TI  - Serum antibody positivity for distinct Helicobacter pylori antigens in benign and
      malignant gastroduodenal disease.
AB  - Infection with Helicobacter pylori may be associated with a variety of
      gastroduodenal diseases. Although H. pylori infection is common, peptic ulcer
      disease and gastric cancer occur in only a small minority of infected persons.
      This work was intended to correlate the pathological findings with the
      serological response to certain H. pylori antigens. Serum samples were taken from
      285 patients who underwent gastroscopy. H. pylori infection was diagnosed by
      histology, culture or rapid urease test (RUT). Serum IgG reactivity against H.
      pylori-specific antigens was studied by Western blot. There was a significant
      association between the diagnosis of gastric cancer and the presence of IgG
      antibodies against the 19.5, 33 and 136 kDa (CagA) antigens. Comparing all H.
      pylori-positive patients with the gastric cancer group for the presence of the
      19.5, 33 and 136 kDa (CagA) antigens, the results were as follows: chi2: 17.482,
      p < 0.001, power P = 0.994, odds ratio (OR) for the presence of gastric cancer:
      19.5 (95% confidence interval (CI): 4.11-92.56). Antibodies against CagA alone or
      other bands (except 33 and 19.5 kDa antigens), as well as the age of patients
      were not related to a diagnosis of gastric cancer. Male patients were more likely
      to develop duodenal ulcer. IgG antibodies against the 19.5, 33 and 136 kDa (CagA)
      antigens could be helpful to identify patients at enhanced risk for the
      development of gastric cancer.

PMID- 16600682
TI  - Investigating bacillary dysentery: the role of laboratory, technique and people.

PMID- 16600681
TI  - Self-associating autotransporters, SAATs: functional and structural similarities.
AB  - The autotransporter family of translocated proteins in Gram-negative bacteria all
      contain three structural motifs, a signal sequence, a passenger domain and a
      translocator domain. The autotransporters constitute a highly versatile group of
      proteins with respect to function, which accords with the widespread presence of
      these proteins. The group encompasses many important virulence factors. In
      Escherichia coli, a subgroup of autotransporter proteins consists of the TibA
      adhesin/invasin associated with some enterotoxigenic E. coli, the AIDA adhesin
      from diarrhea-causing E. coli and finally, the Ag43 autoaggregation factor found
      in the majority of E. coli strains. The three proteins exhibit approximately 25%
      identity at the sequence level, and are quite different with respect to size,
      glycosylation and processing. Nevertheless, they share some important properties:
      all are self-associating proteins that cause bacterial aggregation. They can also
      interact with each other via heterologous interactions to cause formation of
      mixed bacterial aggregates. Furthermore, these proteins enhance biofilm
      formation. Based on these properties we propose to classify them together in a
      group termed SAATs: self-associating autotransporters.

PMID- 16600683
TI  - Synovial sarcoma of the heart.
AB  - We report a case of synovial sarcoma of the heart in a 14-year-old boy, who
      presented with signs of mild generalized illness and rapidly progressed to
      haemodynamic collapse. On operation the tumour was attached to the tricuspid
      valve, away from the atrioventricular node. He was considered to have incomplete
      resection due to extensive adhesions to the atrioventricular junction, and was
      offered chemotherapy. On 18 months follow-up, he was asymptomatic.

PMID- 16600684
TI  - Safety of summer camp for children with chronic and/or life threatening illness.
AB  - The purpose of this work was to retrospectively evaluate the medical needs of
      children with chronic and/or life-threatening illness attending summer camp at
      Barretstown Gang Camp (Ireland). Data on medical facility visits collected over
      28 sessions (2120 children) between 1998 and 2001 were reviewed. Children
      originated from 20 different European countries. The most common diagnoses were
      leukaemia, lymphoma, sarcoma and brain tumour. Forty-eight percent of the
      children required medical care during their stay and 3386 total visits were
      recorded. The most common cause of medical facility visit was pain, followed by
      injury (trauma, bruises, burn) and flu/cold symptoms. Only 8 brief hospital
      transfers were necessary for the 2120 children. This large-scale study confirms
      the safety of a well-organized medically supervised summer therapeutic
      recreational program for children with chronic conditions, including children
      undergoing chemotherapy treatment and factor replacement.

PMID- 16600685
TI  - Involving users in service planning: a focus group approach.
AB  - This paper outlines the way in which a focus group approach was used to involve
      service users in the possible reconfiguration of follow-up services for breast
      cancer patients at a North London hospital. The focus group was used to identify
      the priority issues for users and the development of an objective questionnaire,
      to survey all current service users. Within the National Health Service (NHS) the
      concept of user involvement has been embodied in contemporary health policy, and
      has become an important constituent of current policy direction. This study was
      the first stage of a larger stakeholder project that aimed to involve service
      users and clinicians in developing a new model of breast cancer follow-up
      service. From the focus group emerged five key themes around breast cancer follow
      up. They were: The need for reassurance after the diagnosis of cancer. Continuity
      of care. Privacy and dignity and other elements of the examination technique.
      Information and the detection of new symptoms. The opportunity to discuss
      feelings and worries. In this paper, the nature of breast cancer follow-up
      services is outlined, and the difficulties associated with such services are
      discussed. The background to user involvement within the United Kingdom is
      explored, and the strategies that have previously been used are considered. The
      practical issues involved in using the focus group approach are examined, and the
      experience of using such an approach is outlined in this study. The involvement
      of service users as a key stakeholder in the process of planning change, through
      a participatory research strategy, ensured that their voices were heard alongside
      those of both hospital and primary care staff.

PMID- 16600686
TI  - Potential correlates of BCG induced protection against tuberculosis detected in a
      mouse aerosol model using gene expression profiling.
AB  - Tuberculosis (TB) is responsible for more than 2 million deaths per year with the
      incidence of new cases rising throughout the world. Mycobacterium bovis bacillus
      Calmette Guerin (BCG) is currently the only available licensed vaccine against M.
      tuberculosis. Despite the variable protective efficacy in different populations
      it affords some protection, particularly against childhood and disseminated forms
      of the disease. BCG remains the gold standard for assessing other prospective TB
      vaccines, yet there is a lack of information on the mechanisms of BCG protection
      and consequently there are no definitive correlates of protection for this
      vaccine. In order to further studies in this area we assessed lung RNA
      homogenates from naive, BCG vaccinated and aerosol challenged mice. We found
      increased IFN-gamma levels in lungs of aerosol challenged mice previously
      vaccinated with BCG and a number of transcripts regulated by IFN-gamma were also
      increased in the lungs of these animals. These transcripts represent a cluster of
      IFN-gamma related transcripts that may assist in determining if BCG and maybe
      other potential vaccines will elicit protection against M. tuberculosis.

PMID- 16600687
TI  - Selecting effective siRNA sequences based on the self-organizing map and
      statistical techniques.
AB  - Short interfering RNA (siRNA) has been widely used for studying gene functions in
      mammalian cells but varies markedly in its gene-silencing efficacy. Although many
      design rules/guidelines for effective siRNAs based on various criteria have been
      reported recently, there are only a few consistencies among them. This makes it
      difficult to select effective siRNA sequences in mammalian genes. Here, we
      propose a new method for selecting effective siRNA target sequences on the basis
      of the self-organizing map (SOM) technique and statistical significance analyses
      for a large number of effective siRNAs. In the proposed method, the score is
      defined as a gene degradation measure. The effectiveness for the proposed method
      was confirmed by evaluating effective and ineffective siRNAs for recently
      reported genes (12 genes, 172 siRNA sequences) and comparing with other reported
      scoring methods. The size (value) of this score is closely correlated with the
      degree of gene degradation, and the score can easily be used for selecting high
      potential siRNA candidates. The evaluation results indicate that the proposed
      method would be useful for many other genes. It will therefore be useful for
      selecting siRNA sequences in mammalian genes.

PMID- 16600688
TI  - Polyclonal long-term MFGS-gp91phox marking in rhesus macaques after
      nonmyeloablative transplantation with transduced autologous peripheral blood
      progenitor cells.
AB  - We have recently reported that the RD114-pseudotyped MFGS-gp91phox vector
      achieves unprecedented levels of correction of the NADPH-oxidase gp91phox
      (approved gene symbol CYBB) defect in CD34(+) cells from patients with X-linked
      chronic granulomatous disease in the NOD/SCID mouse model. Considering clinical
      use of this vector, we transplanted autologous mobilized peripheral blood CD34(+)
      progenitor cells, transduced with the RD114-MFGS-gp91phox vector, into two
      healthy rhesus macaques following nonmyeloablative conditioning. The moderately
      high levels of in vivo marking seen in the first months following transduction
      decreased and stabilized at about 8 months posttransplant. Marking for both
      healthy animals after 15 months was 0.3 to 1.3 vector copies per 100 cells in
      lymphocytes, neutrophils, and monocytes. Vector insertion analyses performed by
      linear amplification-mediated PCR and sequencing identified 32 and 45 separate
      insertion sites in the animals. Identical insertion sites were found in myeloid
      cells and lymphocytes, demonstrating the successful transduction of lymphomyeloid
      progenitors. Some inserts landed in the vicinity of genes controlling cell cycle
      and proliferation. Statistical analyses of insertion sites 1 year posttransplant
      suggest a high diversity of insertion sites despite low marking.

PMID- 16600689
TI  - Suppression of angiogenesis, tumor growth, and metastasis by adenovirus-mediated
      gene transfer of human angiotensinogen.
AB  - Angiogenesis is essential for tumor growth and metastatic dissemination. We have
      previously shown that human angiotensinogen (AGT) can in vitro inhibit
      endothelial cell proliferation and migration, capillary-like tube formation, and
      neovascularization. To determine whether AGT can exert an antitumoral effect
      through its antiangiogenic properties, we constructed a recombinant adenovirus
      carrying the human angiotensinogen gene under the control of the cytomegalovirus
      promoter (AdAGT). In vitro studies showed that AdAGT selectively inhibited
      endothelial cell proliferation. In vivo, injections of AdAGT into preestablished
      human MDA-MB-231 mammary carcinomas in nude mice inhibited tumor growth by 70%
      compared to controls, with 21% total regression. This effect was associated with
      the suppression of intratumoral vascularization and marked necrosis. Furthermore,
      in vitroAdAGT infection of MDA-MB-231 and murine melanoma B16F10 cells strongly
      blocked their in vivo tumorigenicity. Then, in mice expressing high levels of AGT
      (i.e., either iv injected with AdAGT or HuAGT transgenic mice), the number of
      B16F10 pulmonary metastases was 85% lower than in control C57BL/6 mice. Our data
      demonstrate that AGT is a very potent antiangiogenic factor in vivo, independent
      of angiotensin II generation. Its delivery by gene transfer represents a
      promising new strategy to block primary tumor growth and to prevent metastasis.

PMID- 16600690
TI  - Hydroxychloroquine-induced restrictive cardiomyopathy.
AB  - Chloroquine (Hydroxychloroquine)-induced cardiomyopathy is a rare but potentially
      life-threatening condition. Cessation of the culprit drug, along with aggressive
      afterload reduction therapy, has been associated with halting of disease progress
      and even improvement in patients' clinical and histologic status.
      Echocardiography is a fundamental tool in the identification and assessment of
      patients with cardiomyopathy, with particular utility in the detailed assessment
      of biventricular systolic and diastolic function. It also provides an objective
      and non-invasive means of assessing treatment response. We present a case of a 51
      year-old woman with hydroxychloroquine-induced restrictive cardiomyopathy and
      correlate clinical, echocardiographic and anatomic pathologic findings both at
      initial presentation and following treatment.

PMID- 16600691
TI  - Transcatheter closure of perimembranous ventricular septal defects with Amplatzer
      occluder assessed by real-time three-dimensional echocardiography.
AB  - We report our initial experience in two patients using real-time three
      dimensional echocardiography to assess perimembranous ventricular septal defect
      and device morphology and their relation with contiguous cardiac structure.
      Defect size and rims as well as device position and profile were displayed from
      the three-dimensional "en face" views. We think that real-time three-dimensional
      echocardiography could be a complementary approach to angiography and
      transesophageal echocardiography in performing transcatheter closure of
      perimembranous ventricular septal defect.

PMID- 16600692
TI  - Real-time three-dimensional echocardiography for regional evaluation of aortic
      stiffness.
AB  - Aortic stiffness is an important predictor of cardiovascular morbidity and
      mortality. Non-invasive measurement of aortic stiffness is a promising challenge
      for echocardiography. The most important limitation of previous studies was that
      regional differences for aortic stiffness were not taken into consideration. In
      our patient, we demonstrated the usefulness of real-time three-dimensional
      echocardiography in assessment of regional aortic stiffness.

PMID- 16600693
TI  - Insulin-related metabolic changes during treatment with valproate in patients
      with epilepsy.
AB  - Weight gain is a known side effect of valproate (VPA) therapy, which is
      associated with hyperinsulinemia and polycystic ovary-like syndrome and
      unfavorable lipid changes in women. Hyperinsulinemia has also been observed in
      male and lean subjects as well. Hyperinsulinemia is associated with several
      health risks, such as cardiovascular diseases and the metabolic syndrome. The
      purpose of this study was to evaluate whether VPA-related hyperinsulinemia is
      associated with other metabolic changes and whether there is any association
      between weight gain, other adverse effects related to VPA, and the metabolic
      syndrome. Fifty-one patients under VPA monotherapy and 45 healthy control
      subjects participated in the study. They were interviewed and clinically
      examined, and, after an overnight fast, blood samples were taken to evaluate
      fasting serum insulin, lipid, free fatty acid, and uric acid levels. Incidence of
      the metabolic syndrome was determined as well. Compared with control subjects,
      VPA-treated patients had higher circulating insulin concentrations relative to
      body mass index, higher uric acid and triglyceride levels, and lower high-density
      lipoprotein cholesterol concentrations. There was no significant difference in
      the frequency of the metabolic syndrome between the VPA-treated patient group and
      the control group. In conclusion, valproate therapy, especially if started at a
      young age, is associated with increased circulating insulin concentrations
      relative to body mass index, indicating that the high insulin levels are not a
      consequence of obesity. Although the frequency of the metabolic syndrome did not
      differ between VPA-treated patients and control subjects, VPA-treated patients
      had higher concentrations of triglycerides and uric acid and lower levels of high
      density lipoprotein cholesterol than control subjects.

PMID- 16600694
TI  - Aspirin and PPAR-alpha activators inhibit monocyte chemoattractant protein-1
      expression induced by high glucose concentration in human endothelial cells.
AB  - Activated endothelial cells express monocyte chemoattractant protein-1 (MCP-1), a
      chemokine which is reportedly involved in the recruitment of plasma monocytes in
      the early stages of atherosclerosis. Since accelerated atherosclerosis is the
      main complication of diabetes and both diseases encompass an inflammatory
      reaction, we hypothesized that the anti-inflammatory drugs, aspirin and
      peroxisome proliferator-activated receptor (PPAR-alpha) activators (fenofibrate
      and clofibrate), could have an effect on the high glucose-induced MCP-1
      expression in endothelial cells. To test this assumption, as well as the possible
      mechanisms involved, the MCP-1 expression and secretion, the reactive oxygen
      species levels, nuclear factor-kB (NF-kB) and activator protein-1 (AP-1)
      expression were determined in human endothelial cells exposed to high glucose
      concentrations in the presence of aspirin, fenofibrate and clofibrate. Human
      endothelial cells kept in normal glucose concentration in the absence of drugs
      were used as control. The results showed that (i) aspirin, fenofibrate and
      clofibrate decrease significantly the MCP-1 expression and secretion in human
      endothelial cells; (ii) the high glucose up-regulated expression of MCP-1 in
      endothelial cells was significantly reduced by inhibitors of NF-kB and reactive
      oxygen species; (iii) all drugs notably decrease the level of the reactive oxygen
      species and activation of NF-kB and AP-1. Together, the findings indicate that in
      endothelial cells aspirin and PPAR-alpha activators reduce the high glucose
      increased expression of MCP-1 by a mechanism that includes the inhibition of
      reactive oxygen species, and decrease of AP-1 and NF-kB activation.

PMID- 16600695
TI  - Sensory receptors in the airways: neurochemical coding of smooth muscle
      associated airway receptors and pulmonary neuroepithelial body innervation.
AB  - Mainly due to the lack of conclusive morphological data, correlation between
      functionally and morphologically defined lung receptors has so far been
      unsatisfactory. In the present study, multiple immunocytochemical stainings with
      a panel of markers for (mechanso)sensory nerve fibres were performed in order to
      visualise putative receptor terminals in rat intrapulmonary airways. We first
      focussed on determining the location, morphology and neurochemical coding of
      subepithelial receptor-like structures that have been sporadically reported in
      the wall of large diameter airways. Immunostaining with antibodies against Na+/K+
      ATPase alpha3, vesicular glutamate transporter 1 (VGLUT1) and VGLUT2 revealed
      branching laminar subepithelial receptor endings associated with airway smooth
      muscle. The latter nerve terminals appeared to further express calbindin D28k
      (CB), and the ATP receptor P2X3, but were calcitonin gene-related peptide (CGRP)
      negative. The nerve fibres that give rise to these terminals were shown to be
      myelinated and have a vagal sensory origin. Because of the close association
      between the laminar terminals of this receptor-like structures and airway smooth
      muscle, we will further refer to these clearly morphologically identifiable
      sensory end organs as 'smooth muscle-associated airway receptors (SMARs)'.
      Secondly, we further explored the sensory innervation of pulmonary
      neuroepithelial bodies (NEBs). NEBs are intraepithelial groups of neuroendocrine
      cells, contacted by several nerve fibre populations, at least three of which are
      sensory. The spinal sensory innervation of NEBs expresses CGRP and substance P,
      contacts NEBs at their basal pole, and is capsaicin-sensitive. The
      intraepithelial vagal sensory innervation of NEBs, on the other hand, appears to
      be myelinated and could be labelled by antibodies against VGLUT1, VGLUT2, CB and
      P2X3 receptors. Na+/K+-ATPase alpha3 immunostaining additionally labelled part of
      the vagal sensory innervation of rat pulmonary NEBs. The neurochemical coding and
      receptor-like appearance of SMARs and of the complex vagal sensory innervation of
      NEBs appeared to be almost identical and reminiscent of mechanosensors. Both
      SMARs and vagal nodose nerve terminals in NEBs therefore likely represent the
      morphological counterparts of subgroups of the extensive population of
      physiologically characterised myelinated vagal airway receptors, the majority of
      which are mechanosensitive. Electrophysiological data based on 'local' stimuli
      should be interpreted with caution, because of the regular close apposition of
      SMARs and NEBs and the very similar characteristics of their nerve terminals.

PMID- 16600696
TI  - Rapid selection of dhfr mutant allele in Plasmodium falciparum isolates after the
      introduction of sulfadoxine/pyrimethamine in combination with 4-aminoquinolines
      in Papua New Guinea.
AB  - To overcome the declining efficacy of the 4-aminoquinolines in Papua New Guinea,
      sulfadoxine/pyrimethamine (SP) was combined with the 4-aminoquinolines as the
      first line treatment for falciparum malaria since 2000. To assess how this change
      had affected SP resistant gene polymorphisms, we determined allele frequencies of
      dhfr and dhps in 113 Plasmodium falciparum isolates from Wewak, East Sepik of
      Papua New Guinea in 2002 and 2003. In dhfr, double mutant (ACNRNVI) was the
      predominant allele with a prevalence of 91%. We found a significant decrease of
      wild dhfr allele prevalence (7%) compared with that reported in the adjacent area
      of East Sepik called the Wosera region (57%), before the drug policy changed in
      1990-1993. Between 2002 and 2003, the prevalence of this allele decreased from
      15% to 3% (P=0.02). Two distinct microsatellite haplotypes flanking dhfr were
      found in isolates with dhfr double mutant, suggesting the selection of
      preexisting SP resistant parasites rather than a frequent occurrence of dhfr
      mutations. The dhfr/dhps quartet mutations (ACNRNVI in dhfr and SGEAA in dhps)
      were identified in six of the isolates (8%) from 2003. This genotype, which is
      associated with in vivo resistance to SP, has not been reported before in Papua
      New Guinea. These findings suggest that isolates resistant to SP were rapidly
      selected despite the use of the SP combination therapy, probably because of their
      preexisting high level of resistance to the 4-aminoquinoline partner drug.

PMID- 16600697
TI  - Cough motor mechanisms.
AB  - Cough is a defensive airway mechanisms which involves the sequential activation
      of several laryngeal and respiratory muscles in the generation of the typical
      four-phase motor pattern. Activation of such muscles can be considered to
      represent the "primary" cough motor mechanism, and its functional significance,
      although complex, appears to be fairly well established. Nonetheless, the
      outflows of cough are numerous, and may additionally involve the reflex or
      mechanical activation of other respiratory and non-respiratory motor systems.
      These additional, or "secondary", outflows of cough can mainly be regarded as
      being involved in either enhancing the defensive function of cough, or opposing
      the possible noxious effects exerted by the mechanical stresses of coughing. In
      addition, both the primary and secondary cough motor mechanisms are known to play
      multiple functional roles, thus considerably complicating the cough panorama.
      Finally, some of the secondary cough motor responses, such as the changes in the
      pattern of breathing, seem to be devoid of any favourable action and their
      functional meaning, if any, is not fully understood. Although it is well known
      that all patterns of cough can be produced voluntarily, the extent to which also
      volitional cough is accompanied by an array of motor responses similar to that of
      reflex cough remains to be elucidated.

PMID- 16600698
TI  - Identification of a metabolite of atrazine, N-ethyl-6-methoxy-N'-(1-methylethyl)
      1,3,5-triazine-2,4-diamine, upon incubation with rat liver microsomes.
AB  - Atrazine is an herbicide which has shown potential antimalarial effects both in
      vitro and in vivo in rats. In order to study the metabolism of atrazine in rat
      livers, we developed a sensitive LC/MS/MS method for the identification of
      atrazine and several of its metabolites. Using this method, we identified one
      previously unreported metabolite with a mass of 211 Da in addition to two known
      metabolites. This new metabolite was confirmed to be N-ethyl-6-methoxy-N'-(1
      methylethyl)-1,3,5-triazine-2,4-diamine, also known as atraton, by comparison of
      the LC/MS/MS mass spectra and the retention time to those of a commercial
      standard.

PMID- 16600699
TI  - Determination of scutellarin in mouse plasma and different tissues by high
      performance liquid chromatography.
AB  - A simple HPLC-UV method was developed for the determination of scutellarin in
      plasma and different tissues of mice (heart, liver, spleen, lungs and kidneys).
      The separation was achieved by HPLC on a Hypersil C(18) column with a mobile
      phase composed of methanol-water-glacial acetic acid (40:60:1). UV detection was
      used at 335 nm. The calibration curves were linear in all matrices (r(2)>0.997)
      in the concentration range of 0.1-10 microg/ml for plasma and 0.1-20 microg/g for
      tissue homogenates, respectively. The method described is suitable for studies on
      the distribution of scutellarin in different tissues of mice.

PMID- 16600700
TI  - Selective protein removal and desalting using microchip CE.
AB  - This paper describes the on-line sample pretreatment and analysis of proteins and
      peptides with a poly(methylmethacrylate) (PMMA) microfluidic device (IonChip).
      This chip consists of two hyphenated electrophoresis channels with integrated
      conductivity detectors. The first channel can be used for sample preconcentration
      and sample clean-up, while in the second channel the selected compounds are
      separated. Isotachophoresis (ITP) combined with zone electrophoresis (CZE) was
      used to preconcentrate a myoglobin sample by a factor of about 65 before
      injection into the second dimension and to desalt a mixture of six proteins with
      100 mM NaCl. However, ITP-CZE could not be used for the removal of two proteins
      from a protein/peptide sample since the protein zone in the ITP step was too
      small to remove certain compounds. Therefore, we used CZE-CZE for the removal of
      proteins from a protein/peptide mixture, thereby injecting only the peptides into
      the second CZE separation channel.

PMID- 16600701
TI  - Studies on the metabolism and toxicological detection of the designer drug 4
      ethyl-2,5-dimethoxy-beta-phenethylamine (2C-E) in rat urine using gas
      chromatographic-mass spectrometric techniques.
AB  - The phenethylamine-derived designer drug 4-ethyl-2,5-dimethoxy-beta
      phenethylamine (2C-E) was found to be mainly metabolized in rats by O
      demethylation, N-acetylation, hydroxylation of the ethyl side chain at C2' or at
      C1' followed by oxidation at C1' to the corresponding ketone, by deamination
      followed by reduction to the corresponding alcohols or by oxidation to the
      corresponding acids, and finally combinations of these steps. Most of the
      metabolites were excreted in conjugated form. The authors' systematic
      toxicological analysis (STA) procedure using full-scan GC-MS allowed the
      detection of an intake of a dose of 2C-E 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-E in human urine.

PMID- 16600702
TI  - On the edge of the denaturation process: application of X-ray diffraction to
      barnase and lysozyme cross-linked crystals with denaturants in molar
      concentrations.
AB  - Structural data about the early step of protein denaturation were obtained from
      cross-linked crystals for two small proteins: barnase and lysozyme. Several
      denaturant agents like urea, bromoethanol or thiourea were used at increasing
      concentrations up to a limit leading to crystal disruption (>or=2 to 6 M). Before
      the complete destruction of the crystal order started, specific binding sites
      were observed at the protein surfaces, an indication that the preliminary step of
      denaturation is the disproportion of intermolecular polar bonds to the benefit of
      the agent "parasiting" the surface. The analysis of the thermal factors first
      agree with a stabilization effect at low or moderate concentration of denaturants
      rapidly followed by a destabilization at specific weak points when the number of
      sites increase (overflooding effect).

PMID- 16600703
TI  - Intrapartum fetal emergencies.
AB  - Labour is one of the shortest yet most hazardous journeys humans take during
      their lifetime. Currently, our methods of identifying those fetuses at particular
      risk of compromise during labour are limited. Antepartum tests of placental
      reserve give little information about an individual fetus's ability to cope with
      passage through the birth canal and some might already have received a silent
      insult earlier in the pregnancy that places them at increased risk. In addition
      to the normal processes of labour, other, more unpredictable factors can act to
      place the fetus in acute danger.

PMID- 16600704
TI  - Bone strength and its determinants in pre- and early pubertal boys and girls.
AB  - Higher fracture rates in women than men may be related to a sex difference in
      bone strength that is thought to emerge during growth. However, sexual dimorphism
      in bone strength and the determinants of bone strength in boys and girls are not
      well understood. Thus, our objectives were to (1) compare tibial bone strength
      and its components (geometry and density) between pre- and early pubertal boys
      and girls and (2) identify the contribution of muscle cross-sectional area and
      other modulating factors to bone outcomes. We used pQCT to assess the distal
      tibia (8%) and tibial midshaft (50%) in 424 Asian and Caucasian pre- and early
      pubertal boys and girls. Our primary outcomes were bone strength index (BSI,
      mg2/mm(4)) at the distal tibia and strength strain index (SSI, mm3) at the
      midshaft. We also assessed components of bone strength including bone geometry
      [total (ToA) and cortical (CoA) cross-sectional areas, mm2] and total (ToD,
      mg/cm3) and cortical (CoD, mg/cm3) density. We used ANCOVA to compare bone
      outcomes between boys and girls in each maturity group (PRE or EARLY pubertal by
      Tanner stage) and multiple regression to evaluate the contribution of muscle
      cross-sectional area (MCSA, mm2 by pQCT), maturity, ethnicity, physical activity,
      dietary calcium, and vertical jump height to bone outcomes. After adjusting for
      tibial length and MCSA, bone strength indices were 6-15% (P < 0.05) greater in
      PRE and EARLY boys compared with PRE and EARLY girls. The sex difference in bone
      strength was due largely to greater bone areas (4-6%) in boys. At the distal
      tibia ToD was significantly greater in PRE boys (6%, P < 0.001) compared with PRE
      girls and at the midshaft CoD was slightly greater in both PRE and EARLY girls
      (1%, P = 0.01). After adjusting for tibial length, MCSA was the primary
      explanatory variable of tibial bone geometry and strength in both sexes
      accounting for 10-16% of the variance. The influence of maturity, ethnicity,
      physical activity, and dietary calcium on pQCT bone outcomes was small and was
      both site- and sex-specific. Sexual dimorphism in tibial bone strength is evident
      in prepuberty. Our results are consistent with a functional model of bone
      development in which bone adapts its geometry and strength to withstand
      challenges from muscle forces during growth.

PMID- 16600708
TI  - Reviewing for journals: ask not what your profession can do for you but what you
      can do for your profession.

PMID- 16600709
TI  - Diagnosing prostate cancer: through a glass, darkly.

PMID- 16600710
TI  - Viral mediated gene therapy for prostate cancer--can we deliver?

PMID- 16600711
TI  - Updating traditional thoughts and concepts in urolithiasis.

PMID- 16600712
TI  - Discharging our duty.

PMID- 16600713
TI  - Diagnostic value of systematic biopsy methods in the investigation of prostate
      cancer: a systematic review.
AB  - PURPOSE: Several new extended prostate biopsy schemes (greater than 6 cores) have
      been proposed. We compared the cancer detection rates and complications of
      different extended prostate biopsy schemes for diagnostic evaluation in men
      scheduled for biopsy to identify the optimal scheme. MATERIALS AND METHODS: In a
      systematic review we searched 13 electronic databases, screened relevant
      urological journals and the reference lists of included studies, and contacted
      experts. We included studies that compared different systematic prostate biopsy
      methods using sequential sampling or a randomized design in men scheduled for
      biopsy due to suspected prostate cancer. We pooled data using a random effects
      model when appropriate. RESULTS: We analyzed 87 studies with a total of 20,698
      patients. We pooled data from 68 studies comparing a total of 94 extended schemes
      with the standard sextant scheme. An increasing number of cores were
      significantly associated with the cancer yield. Laterally directed cores
      increased the yield significantly (p = 0.003), whereas centrally directed cores
      did not. Schemes with 12 cores that took additional laterally directed cores
      detected 31% more cancers (95% CI 25 to 37) than the sextant scheme. Schemes with
      18 to 24 cores did not detect significantly more cancers. Adverse events for
      schemes up to 12 cores were similar to those for the sextant pattern. Adverse
      event reporting was poor for schemes with 18 to 24 cores. CONCLUSIONS: Prostate
      biopsy schemes consisting of 12 cores that add laterally directed cores to the
      standard sextant scheme strike the balance between the cancer detection rate and
      adverse events. Taking more than 12 cores added no significant benefit.

PMID- 16600714
TI  - A systematic review of vitamin D receptor gene polymorphisms and prostate cancer
      risk.
AB  - PURPOSE: Polymorphisms in the vitamin D receptor gene have been hypothesized to
      alter the risk of prostate cancer. However, studies investigating the
      associations between specific vitamin D receptor polymorphisms and prostate
      cancer risk have yielded inconsistent results. MATERIALS AND METHODS: We
      performed a meta-analysis of 26 studies evaluating the association between
      vitamin D receptor TaqI, poly(A), BsmI, ApaI, and/or FokI polymorphisms, and
      prostate cancer risk. RESULTS: The studies were heterogeneous in terms of study
      design, selection of cases and controls, and racial composition. Random effects
      models were used to estimate the pooled OR and 95% CI of each vitamin D receptor
      polymorphism under codominant, additive, dominant and recessive genetic models.
      Overall we did not find evidence to support an association between any of the
      vitamin D receptor polymorphisms and the risk of prostate cancer. For TaqI, which
      is the most studied vitamin D receptor polymorphism with 18 studies (total of
      2,727 cases and 3,685 controls), the pooled OR was 1.00 (95% CI 0.85 to 1.18) for
      the Tt vs TT genotypes, 0.94 (95% CI 0.78 to 1.13) for the tt vs TT genotypes and
      0.89 (95% CI 0.71 to 1.10) for the recessive model (tt vs Tt plus TT). ORs for
      the poly(A) microsatellite, BsmI, ApaI and FokI polymorphisms were similar.
      CONCLUSIONS: The results of this meta-analysis suggest that the vitamin D
      receptor TaqI, poly(A), BsmI, ApaI and FokI polymorphisms are not related to
      prostate cancer risk.

PMID- 16600715
TI  - Symposium report on urothelial dysfunction: pathophysiology and novel therapies.
AB  - PURPOSE: The basic premise of this symposium (Workshop 7) at the 2004
      International Continence Society meeting in Paris was to elucidate different
      mechanisms of urothelial cell pathology, explore their impact on bladder function
      and discuss novel therapeutic interventions. RESULTS: The topics included 1)
      urothelial structure and function, 2) the role of adenosine triphosphate in
      urothelial signaling and cystitis, 3) lamina propria myofibroblasts and
      purinergic receptors, 4) antiproliferative factor involvement in interstitial
      cystitis, 5) the urothelium as a reservoir for bacterial infections, 6) radiation
      cystitis, nitric oxide and gene therapy, and 7) intravesical treatments.
      DISCUSSION: It was agreed that the urothelium can no longer be regarded merely as
      a passive barrier separating urine from the underlying tissues. The epithelial
      cells of the urothelium form part of an integrated network that also includes
      afferent and possibly efferent nerves, and suburothelial myofibroblasts. It has a
      central role in several functions, including bladder wall sensation, local blood
      flow modulation, pathogen removal and active barrier provision. These functions
      are achieved through several autocrine and paracrine pathways that involve
      transmitter release from the urothelium and its ability to integrate incoming
      signals through its battery of membrane receptors. Several pathological processes
      were discussed using this knowledge, including the role of small glycoproteins
      released during interstitial cystitis, the molecular basis of radiation induced
      urothelial damage, the origin of recurrent urinary tract infections and the mode
      of action of potential intravesical treatments for overactive bladder.
      CONCLUSIONS: Overall it was concluded that the urothelium has a key role in
      regulating lower urinary tract physiology and pathology.

PMID- 16600716
TI  - Open partial nephrectomy for tumor in a solitary kidney: experience with 400
      cases.
AB  - PURPOSE: We present a series of 400 patients with tumor in a solitary kidney who
      underwent open surgical partial nephrectomy performed by a single surgeon (ACN)
      with a primary focus on postoperative long-term kidney function. MATERIALS AND
      METHODS: A total of 400 patients with sporadic nonfamilial kidney tumors in a
      solitary kidney underwent open partial nephrectomy between 1980 and 2002. In 323
      patients (81%) the contralateral kidney had been surgically removed, while the
      remaining 77 (19%) had a congenital solitary kidney. Renal insufficiency was
      present preoperatively in 184 patients (46%). Adverse risk factors for partial
      nephrectomy were present in a large percent of patients. Intraoperative and
      postoperative parameters were evaluated at a mean followup of 44 months. RESULTS:
      In the overall series 5 and 10-year cancer specific survival was 89% and 82%,
      respectively. Surgical complications occurred in 52 patients (13%), most commonly
      urinary leakage. Early postoperative renal function was achieved in 398 patients
      (99.5%). Only 2 patients required permanent dialysis postoperatively.
      Satisfactory long-term renal function was achieved in 382 patients (95.5%). A
      total of 18 patients had progressed to renal failure a mean of 3.6 years after
      surgery. Patient age, the amount of renal parenchyma resected, a congenitally
      absent or atrophic contralateral kidney and the time of contralateral nephrectomy
      were noted to be significantly associated with postoperative renal function.
      CONCLUSIONS: Open surgical partial nephrectomy can be safely performed in
      patients with tumor in a solitary kidney. Long-term cancer-free survival with the
      preservation of renal function can be reliably expected in most of these cases.

PMID- 16600718
TI  - The impact of age on the response of patients with superficial bladder cancer to
      intravesical immunotherapy.
AB  - PURPOSE: We determined the influence of age on response to intravesical
      immunotherapy in patients with superficial bladder cancer. MATERIALS AND METHODS:
      Data from a national phase II multicenter trial for BCG plus IFN-alpha
      intravesical therapy for superficial bladder cancer were analyzed. Recurrence
      free survival 2 years after the initiation of therapy was examined in patients by
      incremental age decade. BCG-N patients received 81 mg BCG and 50 MU IFN-alpha,
      while patients who had previously been treated with BCG received a third of the
      BCG dose with 50 MU IFN-alpha and those who were BCG intolerant received a tenth
      of the BCG dose with 100 MU IFN-alpha. Kaplan-Meier survival curves were
      obtained. RESULTS: In all patients the largest difference in response was between
      the 289 who were 61 to 70 years old and the 123 who were older than 80 years with
      a 22% difference in cancer-free survival at a median followup of 24 months (61%
      vs 39%, p = 0.0002). When we assessed BCG-N and BCG treated patients separately
      in the 2 age groups, patients older than 80 years had a persistently lower
      response rate than younger patients 61 to 70 years old. Of BCG-N patients those
      older than 80 and younger than 50 years had the lowest cancer-free survival at a
      median followup of 24 months (47% and 45%, respectively). On multivariate
      analysis age was an independent risk factor for response. CONCLUSIONS: Aging
      appears to be associated with a decreased response to intravesical immunotherapy
      and is particularly apparent in patients older than 80 years. A potential
      explanation could be their depressed baseline immune status and consequent
      inability to mount an immune reaction to BCG or IFN-alpha.

PMID- 16600720
TI  - The effect of repeat transurethral resection on recurrence and progression rates
      in patients with T1 tumors of the bladder who received intravesical mitomycin: a
      prospective, randomized clinical trial.
AB  - PURPOSE: We compared the outcomes of repeat transurethral resection plus
      intravesical mitomycin C with initial transurethral resection of bladder plus
      intravesical MMC in patients with newly diagnosed pT1 transitional cell carcinoma
      of the bladder in terms of recurrence, progression and overall survival.
      MATERIALS AND METHODS: Of 148 newly diagnosed patients with T1 bladder cancer 142
      were prospectively randomized in 2 groups between January 2001 and January 2005.
      A total of 74 patients underwent second TURB and received adjuvant MMC
      intravesically (group 1) and 68 patients received adjuvant MMC following the
      initial TURB (group 2). All repeat TURB operations were performed 2 to 6 weeks
      following initial TURB. Patients with incomplete resection, Cis or muscle
      invasive disease were excluded from study. The first dose of mitomycin C (40 mg
      per week for a total of 8 weeks) was instilled intravesically in all patients
      during the first 24 hours after the last surgery. RESULTS: Mean followup was 31.5
      months (range 6 to 48) with no difference between the 2 groups. The rate of
      recurrence-free survival was 86.35% (SE 0.4%), 77.67% and 68.72% in group 1, and
      47.08%, 42.31% and 37.01% in group 2 for the first, second and third year,
      respectively (overall 74.32% vs 36.76%, log rank 0.0001). Recurrence was observed
      in 19 of the 74 (25.68%) patients in group 1 and in 43 of the 68 (63.24%)
      patients in group 2. Ten of the 19 (52.63%) patients in group 1 and 35 of the 43
      (81.39%) patients in group 2 had recurrence within 12 months. Recurrence was
      observed in 17.6%, 25% and 60% of patients with G1, G2 and G3 tumors,
      respectively, in group 1. The same rates for group 2 were 25%, 64% and 90%. The
      RFS rate was significantly worse in the high grade group (G2 and G3) (p <0.001).
      Progression was observed at 4.05% for group 1 compared to 11.76% for group 2 (log
      rank 0.0974). OS was 91.89% and 89.71% in group 1 and 2, respectively (log rank
      0.732). CONCLUSIONS: The high recurrence rate in patients who did not undergo
      ReTUR is due to a high residual tumor rate following initial TURB. The benefit of
      ReTUR is especially true for high grade tumors. Since intravesical MMC was
      present in both groups, this study has shown that intravesical chemotherapy does
      not compensate for inadequate resection. Progression does not seem to be affected
      by ReTUR although there was a trend favoring the ReTUR group. We recommend ReTUR
      for patients with primary high grade T1 disease to achieve better recurrence-free
      survival.

PMID- 16600721
TI  - Cancer specific outcomes in patients with pT0 disease following radical
      cystectomy.
AB  - PURPOSE: We assessed clinical outcomes in patients found to have no evidence of
      disease, ie pT0, in the cystectomy specimen following radical cystectomy for
      transitional cell carcinoma. MATERIALS AND METHODS: Between 1984 and 2003, 955
      consecutive patients underwent bilateral pelvic lymphadenectomy and radical
      cystectomy for bladder cancer at 3 institutions, namely The Johns Hopkins
      Hospital, University of Texas Southwestern Medical Center and Baylor College of
      Medicine. Excluding nonTCC histology and patients with missing data resulted in
      888 evaluable cases. Primary end points were recurrence-free survival and bladder
      cancer specific survival. RESULTS: Final pathological evaluation revealed absent
      transitional cell carcinoma in the cystectomy specimen, ie pT0, in 59 patients
      (7%), of whom 2 (3%) had pathologically positive lymph nodes. Transurethral
      resection stage or clinical stage data were available on 56 patients (95%),
      including Tis in 5 (9%), Ta in 2 (4%), T1 in 18 (32%), T2 in 29 (52%) and T3 in 2
      (4%). Overall 6 recurrences (10%) were noted, including cTis in 1 case, cT1 in 1,
      cT2 in 3 and cT3 in 1. Median followup in patients with pT0 disease was 56 months
      (range 3 to 183). Three patients (5%) died of bladder cancer and another 4 (7%)
      died of other causes. Five and 10-year bladder cancer progression-free and cancer
      specific survival estimates in patients with pT0 disease were 90% and 81%, and
      95% and 85%, respectively. CONCLUSIONS: Despite excellent clinical outcomes in
      the majority of patients with no evidence of tumor on final pathological
      evaluation not all patients with pT0 disease in the cystectomy specimen are cured
      of bladder cancer. These events may even occur in patients with nonmuscle
      invasive or muscle invasive organ confined pathology at staging transurethral
      resection. Further study is needed to identify prognostic factors in this
      population.

PMID- 16600723
TI  - Clinical usefulness of serum prostate specific antigen for the detection of
      prostate cancer is preserved in men receiving the dual 5alpha-reductase inhibitor
      dutasteride.
AB  - PURPOSE: We determined whether the decrease in serum PSA seen with 5alpha
      reductase inhibitors affects the clinical usefulness of PSA for prostate cancer
      screening using data from 2 dutasteride benign prostatic hyperplasia studies.
      MATERIALS AND METHODS: A total of 2,802 men 50 years or older with a clinical
      diagnosis of benign prostatic hyperplasia, no history of prostate cancer, PSA 1.5
      to 10 ng/ml, prostate volume 30 cc or greater, an American Urological Association
      symptom score of 12 or greater and peak urinary flow rate 15 ml per second or
      less were randomized to 0.5 mg dutasteride daily or matching placebo for 24
      months. Increases in PSA from baseline and the maximum increase from nadir to
      month 24 were compared between the groups and analyzed by prostate cancer status,
      as determined by PSA driven biopsy and an advised cutoff of more than 4 ng/ml
      after doubling to correct for dutasteride treatment with sensitivity and
      specificity calculated for each. RESULTS: In placebo treated men without prostate
      cancer there was an 8.3% median increase in PSA at month 24 compared with -59.5%
      in those who received dutasteride, using doubled values to correct for
      dutasteride treatment. In those with prostate cancer these changes were 23.8% and
      -37.2%, respectively. Using the upper PSA limit of 4 ng/ml sensitivity for
      prostate cancer in men receiving dutasteride vs placebo was 0.737 vs 0.804, while
      specificity was 0.671 vs 0.578. Using a PSA increase from nadir of 0.8 ng/ml the
      sensitivity of dutasteride was 0.548 and its specificity was 0.795. CONCLUSIONS:
      A doubling factor is effective for maintaining the sensitivity and specificity of
      PSA for prostate cancer detection in men on dutasteride. Increases in serum PSA
      in men receiving dutasteride should be considered suspicious and serial PSA
      measurements should be used to evaluate changes from nadir.

PMID- 16600724
TI  - Preoperative serum prostate specific antigen remains a significant prognostic
      variable in predicting biochemical failure after radical prostatectomy.
AB  - PURPOSE: Multiple investigators have argued that PSA may no longer be an accurate
      marker of prostate cancer biology. We determined whether the impact of PSA in
      predicting biochemical failure after radical prostatectomy has changed since the
      beginning of the PSA era. MATERIALS AND METHODS: A total of 1,246 patients were
      identified from the Columbia University Comprehensive Urological Oncology
      Database who underwent radical prostatectomy by 1 of 3 surgeons between 1988 and
      2003. Cox proportional hazards models were fit to the data to estimate the impact
      of PSA (logPSA) in predicting BCF (PSA 0.2 ng/ml or greater). To determine if the
      predictive impact of PSA changed over time, patients were classified based on
      year of surgery, and an interaction term between PSA and time was included.
      Finally concordance indexes were estimated to determine if the predictive ability
      of PSA has changed over time. RESULTS: In a Cox model including PSA, year of
      surgery and a year/PSA interaction term, the impact of PSA appears to change over
      time (p = 0.002). However, when correcting for the effects of stage and grade
      there was no significant change in the impact of PSA. In addition, concordance
      analysis indicated that the predictive ability of PSA has remained constant
      throughout the PSA era (0.65, 0.66 and 0.64 for each period, respectively).
      CONCLUSIONS: This study demonstrates that the predictive ability of PSA as a
      cancer outcomes biomarker has not changed significantly since the beginning of
      the PSA era. Despite suggestions to the contrary, PSA remains an important
      variable in predicting risk of BCF after RP.

PMID- 16600726
TI  - The impact of a negative (111)indium-capromab pendetide scan before salvage
      radiotherapy.
AB  - PURPOSE: We determined the prognostic role, if any, of the ProstaScint
      (111)indium-capromab pendetide scan before salvage radiotherapy for biochemical
      recurrence after RP for localized prostate cancer. MATERIALS AND METHODS: We
      reviewed the records of 649 patients who underwent a ProstaScint scan from 1998
      to 2004. A total of 44 patients were identified who had biochemical recurrence
      after RP and underwent a ProstaScint scan immediately before salvage
      radiotherapy. All patients received salvage radiotherapy to the prostatic bed
      unless pelvic lymph node uptake was identified on the scan, resulting in initial
      whole pelvic radiotherapy with 45 Gy, followed by a conformal boost to the
      prostate bed in 6. The median salvage radiotherapy dose to the prostate bed was
      72 Gy. Patient demographics, pathological information, PSA values and ProstaScint
      results were collected retrospectively. The majority of ProstaScint scans were
      digitally fused with noncontrast pelvic computerized tomography images for
      interpretation. PSA progression after radiotherapy was defined using American
      Society for Therapeutic Radiation and Oncology criteria. RESULTS: At a mean
      followup of 22 months 43 of 44 patients (97%) experienced a PSA decrease after
      salvage radiotherapy with a mean PSA nadir of 0.16 ng/ml compared to a mean pre
      radiotherapy PSA of 1.7 ng/ml. Of the 44 patients 15 (34%) showed post
      radiotherapy PSA progression. When the entire cohort was analyzed, patients with
      negative ProstaScint scans had statistically lower post-radiotherapy PSA
      progression rates than patients with positive scans (1 of 10 or 10% vs 14 of 34
      or 41%, p = 0.026). Patients with negative ProstaScint results were also
      statistically more likely to have a pre-radiotherapy PSA of less than 1.0 ng/ml
      (p = 0.005), no seminal vesicle involvement (p = 0.006), a greater mean PSA
      doubling time (p = 0.008) and received no hormone therapy (p = 0.003). When
      patients with pre-radiotherapy PSA less than 1.0 ng/ml were analyzed, a negative
      ProstaScint scan suggested but did not provide a statistically significant
      advantage over pre-radiotherapy PSA alone for predicting post-radiotherapy PSA
      progression (1 of 9 or 11% for negative vs 5 of 15 or 33% for positive scans, p =
      0.20). CONCLUSIONS: Our early experience supports an improved prognosis in
      patients receiving salvage pelvic radiotherapy for biochemical recurrence after
      RP who have a negative pre-radiotherapy ProstaScint scan. However, this finding
      is not necessarily independent of pre-radiotherapy PSA.

PMID- 16600727
TI  - Intermittent use of testosterone inactivating pharmaceuticals using finasteride
      prolongs the time off period.
AB  - PURPOSE: Men with prostate cancer treated intermittently with TIP benefit from
      improved quality of life when TOP with recovered testosterone is prolonged. We
      examined factors influencing the duration of TOP. MATERIALS AND METHODS: We
      retrospectively reviewed the charts of 101 men treated with intermittent TIP in a
      9-year period. Men with positive bone scan, men in whom a PSA nadir of less than
      0.1 ng/ml on TIP failed to be achieved and maintained and men in whom
      testosterone failed to recover to greater than 150 ng/dl during the first 12
      months of TOP were excluded. Potential factors predicting prolonged TOP or
      accelerated time to AIPC were studied with Cox regression analysis. RESULTS:
      Patient characteristics were clinical stage T1c-T2a in 51 and T2b-T3b in 11, PSA
      relapse in 29, and T3c, D0 or D1 in 10. Median PSA was 7.6 ng/ml, Gleason score
      was 3 + 4 = 7 and TIP duration was 15.8 months. The 60 group 1 patients received
      finasteride and the 41 in group 2 received no finasteride. Median TOP in groups 1
      and 2 was 31 and 15 months, respectively, using Kaplan-Meier analysis. Cox
      regression analysis indicated that longer TIP, finasteride and increased age
      predicted longer TOP. A slow PSA decrease while on TIP, higher baseline PSA and
      increased Gleason score predicted shorter TOP. Cox regression analysis indicated
      that only higher clinical stage but not finasteride predicted the earlier onset
      of AIPC. CONCLUSIONS: Finasteride doubles the duration of TOP. AIPC was not
      increased by finasteride after almost 9 years of observation.

PMID- 16600728
TI  - Bone mineral density changes in patients with prostate cancer during the first 2
      years of androgen suppression.
AB  - PURPOSE: We characterized bone mineral density changes in patients with prostate
      cancer on androgen deprivation therapy during the first 2 years of uninterrupted
      therapy, and identified which location most reflects bone mass loss. MATERIALS
      AND METHODS: Using dual energy x-ray absorptiometry, bone mineral density was
      prospectively assessed in patients with nonmetastatic prostate cancer at the
      lumbar spine and femoral neck, Ward's triangle, trochanter and total hip.
      Measurements were performed at baseline and yearly thereafter in patients on ADT,
      and at baseline and 1 year in controls (age matched patients with prostate
      cancer, free of biochemical progression after radical prostatectomy). RESULTS: A
      total of 62 patients were included in the study, 31 in each group. Median age (70
      and 69 years, respectively), mean Gleason score and mean baseline serum
      testosterone did not significantly differ. Patients receiving ADT experienced a
      significant bone mass loss at 12 months in all locations, ranging from 2.29% to
      5.55% (p <0.001). In contrast, bone mineral density did not change significantly
      (0.64% to 1.68%) in patients not receiving ADT. In the 20 patients on ADT after
      24 months, the second year decrease was not as severe, nor was it significant
      compared to first year values. The major bone mass loss occurred in Ward's
      triangle, with decreases of 5.55% at 12 months and 7.05% at 24 months.
      CONCLUSIONS: Bone mineral density decreases during the first 24 months of
      androgen suppression with the most relevant effect occurring in the first year.
      Ward's triangle is the axial skeletal site that reflects the major bone mass
      loss. Because the deleterious impact of long-term androgen suppression on bone
      mineral density is inversely related to fracture risk and indirectly related to
      survival in patients with prostate cancer, early diagnosis and prevention of bone
      mass loss are warranted in these patients.

PMID- 16600730
TI  - Increasing prostate specific antigen following radical prostatectomy and adjuvant
      hormonal therapy: doubling time predicts survival.
AB  - PURPOSE: Adjuvant hormonal therapy may be beneficial in patients who are treated
      with RRP and found to have adverse pathological findings. We assessed the natural
      history of detectable PSA in such patients with particular emphasis on the
      prognostic usefulness of PSADT. MATERIALS AND METHODS: We identified 903 patients
      treated with RRP and adjuvant hormonal therapy (started less than 90 days
      postoperatively) for prostate cancer at our institution between 1990 and 1999.
      PSADT was calculated by log linear regression in men with 2 or more PSA
      measurements available at least 90 days apart. CSS and sRFS were estimated by the
      Kaplan-Meier method and analyzed using Cox proportional hazard models. RESULTS:
      At a median followup of 9.1 years PSA had become detectable in 369 of 771
      patients (47.9%) who achieved an undetectable nadir. PSADT evaluable in 463
      patients was less than 12 months in 68 (14.6%) and more than 10 years in 283
      (61.1%). N stage and Gleason score were significantly associated with sRFS and
      CSS. PSADT was a significant predictor of sRFS and CSS in N+ and N0 cases with a
      cancer death HR of 0.55 (95% CI 0.43 to 0.71) and 0.50 (95% CI 0.31 to 0.79),
      respectively. The association between PSADT and survival persisted after
      multivariate adjustment for preoperative PSA, specimen Gleason score and seminal
      vesicle invasion. CONCLUSIONS: This study demonstrates that many patients have
      slow progression despite increasing PSA following RRP and adjuvant hormonal
      therapy. Nodal status, cancer grade and PSADT are predictive of sRFS and CSS, and
      may be a useful means of selecting patients for future adjuvant therapy trials.

PMID- 16600732
TI  - Laparoscopic versus open simple prostatectomy: a comparative study.
AB  - PURPOSE: Laparoscopic simple prostatectomy has recently been developed to remove
      large prostatic adenomas causing bladder outflow obstruction. To our knowledge
      the advantages of the laparoscopic vs the standard open approach to this
      procedure remain undefined. We compared laparoscopic and open simple
      prostatectomy. MATERIALS AND METHODS: Perioperative data on the first 30
      consecutive laparoscopic simple prostatectomies performed by 1 surgeon were
      collected prospectively and compared with retrospectively collected data on a
      series of 30 consecutive open simple prostatectomies. A Millin and a transvesical
      prostatic technique were used in the laparoscopic group and a transvesical
      technique was used in the open group. RESULTS: There was no significant
      difference in prostatic size, patient age or body mass index between the 2
      groups. In the laparoscopic group the mean International Prostate Symptom score
      +/- SD improved from 22.4 +/- 6.9 to 5.7 +/- 3.6 and the urinary flow rate
      improved from 8.1 +/- 2.5 to 24.6 +/- 12.1 ml per minute (each p <0.001). Mean
      total blood loss (367 +/- 363 vs 643 +/- 647 ml), irrigation time (0.33 +/- 0.7
      vs 4 +/- 3.5 days), duration of catheterization (4 +/- 1.7 vs 6.8 +/- 4.7 days)
      and hospital stay (5.1 +/- 1.8 vs 8 +/- 4.8 days) were significantly less in the
      laparoscopic group than in the open group. Mean operative time was longer in the
      laparoscopic group (115 +/- 30 vs 54 +/- 19 minutes). Of the 30 patients in the
      laparoscopic group 24 did not require bladder irrigation. There was no apparent
      difference in the incidence or severity of complications. There was no difference
      in perioperative parameters or functional results between the 2 different
      laparoscopic techniques. CONCLUSIONS: Laparoscopic simple prostatectomy has
      inherent advantages over the open technique. Further studies are indicated to
      determine whether this technique should be considered the treatment of choice for
      prostatic adenomas too large for safe endoscopic resection.

PMID- 16600733
TI  - Tertiary Gleason pattern 5 is a powerful predictor of biochemical relapse in
      patients with Gleason score 7 prostatic adenocarcinoma.
AB  - PURPOSE: In radical prostatectomy specimens Gleason score 7 is among the most
      commonly assigned scores for prostate carcinoma accounting for 30% to 50% of
      cases. Gleason score 7 is different from other more differentiated prostate
      carcinomas (tumors of Gleason scores 5 and 6) with a significantly worse outcome
      and higher rate of recurrence. Nonetheless, Gleason score 7 tumors are
      heterogeneous. In this study we examined the differences in clinical outcome
      between primary Gleason grade 3 and 4 tumors in patients who underwent radical
      prostatectomy, and determined the influence of tertiary Gleason pattern 5 on
      patient outcome. MATERIALS AND METHODS: A total of 504 patients underwent radical
      prostatectomy for prostate cancer and 228 of the patients (45%) had a Gleason
      score of 7. Cases were analyzed for a variety of clinical and pathological
      parameters. The influence of primary Gleason pattern and tertiary Gleason pattern
      5 on patient outcome was assessed in the Cox regression model. RESULTS: Among 228
      patients with Gleason score 7 prostatic adenocarcinoma, 91 (40%) had a primary
      Gleason pattern 4 and 137 (60%) had primary Gleason pattern 3. Patients of the
      former group were more likely to have a higher pathological stage (p = 0.003),
      more likely to have PSA recurrence (p = 0.02) and more likely to have a tertiary
      Gleason pattern 5 (p <0.0001). A total of 37 (41%) patients with primary Gleason
      4 had a tertiary Gleason pattern 5, whereas only 13 (9%) patients with primary
      Gleason 3 had a tertiary Gleason pattern 5. In the Cox regression model
      controlling for tumor stage and surgical margin status, the primary Gleason
      pattern was not an independent predictor of PSA recurrence (p = 0.80), whereas
      the presence of tertiary Gleason pattern 5 was a significant predictor of PSA
      recurrence (hazard ratio 2.10, 95% CI 1.24-3.55, p = 0.006). Five-year PSA
      recurrence-free survival was 70% for patients without a tertiary Gleason pattern
      5 compared to 19% for those patients with a tertiary Gleason pattern 5.
      CONCLUSIONS: Among patients with Gleason score 7, primary Gleason grade 4
      indicates a likelihood of higher tumor stage and higher probability of PSA
      recurrence than does primary pattern 3. However, it does not independently
      predict a worse outcome after controlling for other known prognostic parameters
      associated with disease progression. Regardless of whether the primary Gleason
      pattern is 3 or 4, a tertiary Gleason pattern 5 is the strongest predictor of a
      worse outcome in patients with Gleason grade 7 prostatic adenocarcinoma.
      Therefore, tertiary pattern 5 should be reported in radical prostatectomy
      specimens.

PMID- 16600735
TI  - Nomogram predictive of pathological inguinal lymph node involvement in patients
      with squamous cell carcinoma of the penis.
AB  - PURPOSE: In penile cancer the therapeutic benefits of early inguinal
      lymphadenectomy must be counterbalanced by the high rates of morbidity,
      postoperative complications and mortality. A relevant aim is optimizing the
      selection of the patients who could really have the highest survival advantage
      from inguinal lymphadenectomy, limiting the cases in which this surgery might be
      considered over treatment with a risk of severe complications. We generated a
      nomogram estimating the risk of pathological inguinal lymph node involvement
      according to clinical lymph node stage and pathological findings of the primary
      tumor. MATERIALS AND METHODS: We retrospectively collected the clinical and
      pathological data of 175 patients who had undergone surgical therapy for squamous
      cell carcinoma of the penis from 1980 to 2002 at 11 urological centers in
      northeastern Italy. A logistic regression model was used to construct the
      nomogram. RESULTS: The presence of palpable groin lymph nodes and the
      histological findings of vascular and/or lymphatic embolization were important
      predictors of metastatic inguinal lymph node involvement. The nomogram predicting
      the risk of metastatic lymph node involvement showed a good concordance index
      (0.876) and good calibration. CONCLUSIONS: The clinical stage of groin lymph
      nodes and pathological findings of penectomy specimens allowed us to generate a
      nomogram to predict the probability of metastatic lymph node involvement in
      patients with squamous cell carcinoma of the penis. The statistical model showed
      an excellent ability to identify the patients with lymph node metastases and good
      calibration.

PMID- 16600737
TI  - Intestinal oxalate absorption is higher in idiopathic calcium oxalate stone
      formers than in healthy controls: measurements with the [(13)C2]oxalate
      absorption test.
AB  - PURPOSE: We assessed the importance of oxalate hyperabsorption for idiopathic
      calcium oxalate urolithiasis, oxalate absorption in healthy volunteers and
      recurrent calcium oxalate stone formers was compared. MATERIALS AND METHODS: The
      [(13)C2]oxalate absorption test, a standardized, radioactivity-free test, was
      performed. On 2 days 24-hour urine was collected and an identical standard diet
      containing 800 mg Ca daily was maintained. On the morning of day 2 a capsule
      containing 0.37 mmol sodium [(13)C2]oxalate was ingested. A total of 120 healthy
      volunteers (60 women and 60 men) and 120 patients (30 women and 90 men) with
      idiopathic CaOx urolithiasis (60% or greater CaOx) were tested. RESULTS: Mean
      intestinal oxalate absorption in the volunteers was 8.0 +/- 4.4%, and in the
      patients was 10.2 +/- 5.2% (p <0.001). There was no significant difference in
      mean absorption values between men and women within both groups. A high overlap
      between the absorption values of volunteers and patients was found. Only in the
      patient group did absorption values greater than 20% occur. Oxalate absorption
      correlated with oxalate excretion in the patients, r = 0.529 (p <0.01) and in the
      volunteers, r = 0.307 (p <0.01). CONCLUSIONS: In high oxalate absorbers dietary
      oxalate has a significant role in oxalate excretion and, therefore, increases the
      risk of calcium oxalate stone formation.

PMID- 16600738
TI  - Changing composition of renal calculi in patients with neurogenic bladder.
AB  - PURPOSE: Renal calculi are a significant source of morbidity for patients with
      neurogenic bladder. Calculi from patients with NB have traditionally been
      composed primarily of struvite and carbonate apatite secondary to chronic urea
      splitting bacteriuria. In the current era there have been great improvements in
      the urological rehabilitation of patients with NB. We defined the composition of
      renal calculi in a contemporary cohort of patients with NB due to spinal cord
      injury or myelomeningocele who underwent percutaneous nephrolithotomy. MATERIALS
      AND METHODS: We performed a retrospective evaluation of all patients with NB due
      to SCI or MM who underwent PNL between January 2002 and January 2005. RESULTS: A
      total of 32 patients with NB (14 with SCI, 18 with MM) underwent PNL in this
      period. Stones were infectious in etiology in 37.5% (12 struvite/carbonate
      apatite) and metabolic in 62.5% (1 uric acid, 2 calcium oxalate monohydrate, 2
      brushite, 6 hydroxyapatite, 9 mixed hydroxyapatite/calcium oxalate). All patients
      with struvite calculi were infected with urea-splitting bacteria on preoperative
      urine culture. CONCLUSIONS: Patients with neurogenic bladder are traditionally
      thought to harbor infection related calculi. These data demonstrate that many
      contemporary patients will be found to have calculi of a metabolic etiology.
      Although patients with NB still have renal calculi, advances in urological
      treatment may have affected the composition of their calculi, as metabolic stones
      are becoming more commonly identified. When metabolic components are identified,
      stone activity may be attenuated with appropriate metabolic evaluation,
      pharmacological therapies and dietary modifications.

PMID- 16600740
TI  - Endoscopic evidence of calculus attachment to Randall's plaque.
AB  - PURPOSE: It has been proposed that calcium oxalate calculi begin as small stones
      attached to the renal papillae at sites of Randall's plaque. However, no study
      has investigated the prevalence of attached stones in calcium oxalate stone
      formers or the relationship between stone attachment site and Randall's plaque.
      In this study we used endoscopic examination of renal papillae in stone formers
      undergoing percutaneous nephrolithotomy to investigate both issues. MATERIALS AND
      METHODS: Idiopathic calcium oxalate stone formers undergoing PNL for stone
      removal were enrolled in this study. Multiple papillae were examined and images
      were recorded by digital video. The presence or absence of papillary plaque and
      attached stones was noted, as was the site of stone attachment. RESULTS: In 23
      patients, 24 kidneys and 172 renal papillae were examined. All kidneys were found
      to have papillary plaque and 11 of the patients had attached stones. Most
      papillae (91%) contained plaque. CONCLUSIONS: The prevalence of attached stones
      in calcium oxalate stone formers (48%) is greater than that previously reported
      for the general population. Attachment appears to be on Randall's plaque. The
      high prevalence of attached stones and the appearance of the attachment site are
      consistent with a mechanism of calcium oxalate stone formation in which stones
      begin as plaque overgrowth.

PMID- 16600742
TI  - Alternate or additional findings to stone disease on unenhanced computerized
      tomography for acute flank pain can impact management.
AB  - PURPOSE: We evaluated the incidence and clinical relevance of alternate or
      additional findings on unenhanced CT in patients with acute flank pain and
      suspected urinary calculi. MATERIALS AND METHODS: A consecutive series of 1,500
      patients underwent unenhanced CT due to acute flank pain. The absence or presence
      of urinary tract calculi and their localization were recorded. Alternate or
      additional CT findings were classified according to whether they required
      immediate or deferred treatment, or were of little or no clinical importance.
      RESULTS: Of the 1,500 patients 1,035 (69%) had urinary tract calculi, including
      309 (30%) with nephrolithiasis, 377 (36%) with ureterolithiasis and 349 (34%)
      with the 2 conditions. Urolithiasis alone was found in 331 of these patients
      (32%) and additional pathological conditions were noted in 704 (68%). Of all
      patients 1,064 (71%) had other or additional CT findings. Of all patients 207
      (14%) had nonstone related CT findings requiring immediate or deferred treatment,
      464 (31%) had pathological conditions of little clinical importance and 393 (26%)
      had pathological conditions of no clinical relevance. CT was normal in 105 of all
      patients (7%). CONCLUSIONS: Unenhanced CT in patients with acute flank pain
      allows the accurate diagnosis of urinary stone disease and it can also provide
      further important information leading to emergency or deferred treatment in a
      substantial number of patients.

PMID- 16600744
TI  - Temporal trends in the use of percutaneous nephrolithotomy.
AB  - PURPOSE: Treatment for nephrolithiasis has evolved because of the dissemination
      of less invasive techniques, such as ureteroscopy and shock wave lithotripsy. We
      examined temporal trends in PCNL use and characterized the determinants of a
      prolonged LOS and in-hospital mortality to provide insight into the evolution of
      practice patterns for nephrolithiasis treatment. MATERIALS AND METHODS: We
      abstracted data on 12,948 patients undergoing percutaneous procedures for urinary
      calculi between 1988 and 2002 from the Nationwide Inpatient Sample using
      International Classification of Disease, 9th revision, Clinical Modification
      procedure and diagnostic codes. A weighted sample was used to estimate national
      PCNL use rates. Adjusted models were constructed to measure the association of
      hospital structure and patient demographics with mortality and a prolonged LOS
      (greater than 90th percentile). RESULTS: Annual PCNL use increased temporally
      during the study from 1.2/100,000 to 2.5/100,000 United States residents (p
      <0.0001). The in-hospital mortality rate was low at 0.2%, although a volume
      outcome relationship was still evident (high and low volume 0.1% and 0.2%,
      respectively, p = 0.002). Treatment at hospitals with lower hospital PCNL volume
      and lower discharge volume (all diagnoses) was associated with an increasing
      likelihood of in-hospital mortality (each p <0.01). CONCLUSIONS: Despite the
      advent of less invasive techniques PCNL remains a popular means of managing stone
      disease. Although mortality was rare, it was significantly lower at high than at
      low volume hospitals. Low short-term mortality rates coupled with shorter LOS and
      high success rates may make PCNL increasingly palatable from a patient
      perspective and provide a potential basis for its increasing use.

PMID- 16600745
TI  - Transcutaneous electrical nerve stimulation: an effective treatment for pain
      caused by renal colic in emergency care.
AB  - PURPOSE: Acute renal colic is one of the most anguishing forms of pain in humans.
      We hypothesized that TENS is an effective pain treatment in patients with acute
      renal colic. MATERIALS AND METHODS: A total of 100 patients with acute flank pain
      and suspected renal colic consented to participate in our study. Paramedic 1
      recorded baseline parameters at the emergency site and at the end of
      transportation. Paramedic 2 performed TENS in patients randomly assigned to G1
      with actual TENS or to G2 with sham TENS. Pain and anxiety were measured using
      paper based visual analog scales on a scale of 0 to 100 mm. RESULTS: Of 100
      screened patients 73 had renal colic, including 39 in G1 and 34 in G2. There was
      no significant difference with regard to potentially influencing factors, such as
      patient age, sex, weight, height, blood pressure and heart rate, pain, nausea and
      anxiety between the groups before treatment. G1 showed a significant mean pain
      decrease +/- SD of more than 50% (85.7 +/- 10.5 to 33.3 +/- 16.0 mm, p <0.01). G2
      showed no variation in mean pain scores (85.8 +/- 18.0 to 82.6 +/- 14.3 mm). G1
      showed changes in the mean anxiety score (69.0 +/- 8.4 to 37.7 +/- 15.1 mm, p
      <0.01), nausea score (90.7 +/- 9.2 to 44.9 +/- 22.0 mm) and heart rate (92 +/- 10
      to 64 +/- 8 bpm), while G2 showed nonsignificant changes. CONCLUSIONS: This trial
      shows that local TENS is a rapid and effective treatment for renal colic pain. We
      found TENS to be a good nondrug therapy under the difficult circumstances of out
      of hospital rescue.

PMID- 16600747
TI  - Diabetes mellitus and hypertension associated with shock wave lithotripsy of
      renal and proximal ureteral stones at 19 years of followup.
AB  - PURPOSE: SWL has revolutionized the management of nephrolithiasis and it is a
      preferred treatment for uncomplicated renal and proximal ureteral calculi. Since
      its introduction in 1982, conflicting reports of early adverse effects have been
      published. However, to our knowledge the long-term medical effects associated
      with SWL are unknown. We evaluated these adverse medical effects associated with
      SWL for renal and proximal ureteral stones. MATERIALS AND METHODS: Chart review
      identified 630 patients treated with SWL at our institution in 1985.
      Questionnaires were sent to 578 patients who were alive in 2004. The response
      rate was 58.9%. Respondents were matched by age, sex and year of presentation to
      a cohort of patients with nephrolithiasis who were treated nonsurgically.
      RESULTS: At 19 years of followup hypertension was more prevalent in the SWL group
      (OR 1.47, 95% CI 1.03, 2.10, p = 0.034). The development of hypertension was
      related to bilateral treatment (p = 0.033). In the SWL group diabetes mellitus
      developed in 16.8% of patients. Patients treated with SWL were more likely to
      have diabetes mellitus than controls (OR 3.23, 95% CI 1.73 to 6.02, p <0.001).
      Multivariate analysis controlling for change in body mass index showed a
      persistent risk of diabetes mellitus in the SWL group (OR 3.75, 95% CI 1.56 to
      9.02, p = 0.003). Diabetes mellitus was related to the number of administered
      shocks and treatment intensity (p = 0.005 and 0.007). CONCLUSIONS: At 19 years of
      followup SWL for renal and proximal ureteral stones was associated with the
      development of hypertension and diabetes mellitus. The incidence of these
      conditions was significantly higher than in a cohort of conservatively treated
      patients with nephrolithiasis.

PMID- 16600748
TI  - Complex posterior urethral disruptions: management by combined abdominal
      transpubic perineal urethroplasty.
AB  - PURPOSE: We present our short-term results of abdominal transpubic perineal
      urethroplasty for complex posterior urethral disruption. MATERIALS AND METHODS:
      From January 2000 to March 2005, 21 patients with complex posterior urethral
      disruption underwent abdominal transpubic perineal urethroplasty. Complex
      disruption was defined as stricture gap exceeding 3 cm or associated perineal
      fistulas, rectourethral fistulas, periurethral cavities, false passages, an open
      bladder neck or previous failed repair. Preoperative voiding cystourethrogram
      with retrograde urethrogram and cystourethroscopy were done to evaluate the
      stricture and bladder neck. Followup consisted of symptomatic assessment and
      voiding cystourethrogram. RESULTS: There were 11 adults and 10 prepubescent boys
      with an average age of 26 years (range 6 to 62). Mean followup +/- SD was 28
      months (range 9 to 40). Mean stricture length was 5.2 +/- 1.4 cm. Of the 21
      patients 12 had previously undergone failed urethroplasty. The mean period
      between original trauma/failed repair and definitive repair was 10.2 +/- 4.3
      months. Urethroplasty was achieved through the subpubic route in 16 patients,
      while 5 required supracrural rerouting. In 20 of 21 patients (95%) postoperative
      cystourethrography showed a wide, patent anastomosis. Postoperative incontinence
      developed in 2 of 21 patients (9.5%). Seven of the 21 patients (33%) were
      impotent after the primary injury, while 3 of 14 (21.4%) had impotence
      postoperatively. There were no complications related to pubic resection, bowel
      herniation or periurethral cavity recurrence. CONCLUSIONS: Combined abdominal
      transpubic perineal urethroplasty is a safe procedure in children and adults. It
      allows wide exposure to create a tension-free urethral anastomosis without
      significantly affecting continence or potency. Complications of pubic resection
      are now rarely seen.

PMID- 16600750
TI  - Evaluation of ureterointestinal anastomosis: Wallace vs Bricker.
AB  - PURPOSE: There are no published reports to our knowledge comparing the
      complication rates of the 2 most frequently used ureterointestinal anastomoses.
      We compared the Bricker method vs the Wallace method in terms of stricture rate.
      MATERIALS AND METHODS: A retrospective review of the cystectomy database at our
      institution covering 1997 to 2003 was conducted. Patients were reviewed in terms
      of type of anastomosis, stricture formation, intervention, radiation therapy,
      type of diversion, operating room time, sex and age. RESULTS: A total of 237
      patients at our institution underwent cystectomy during the time evaluated. Of
      these patients, 33 had incomplete data, 2 were anephric and did not require
      diversion, and 4 patients underwent LeDuc anastomosis. These patients were
      excluded from analysis, leaving 198 patients, 86 (43%) undergoing Bricker and 112
      (56%) undergoing Wallace. Bricker anastomoses were considered 2 anastomotic units
      while Wallace anastomoses were considered a single unit. Therefore, there were
      162 (59%) total Bricker anastomoses compared to 112 (41%) Wallace anastomoses.
      There was no statistically significant difference between the 2 groups in terms
      of type of diversion, number of patients undergoing adjuvant or neoadjuvant
      radiation therapy, operating room time, and days of followup. There were 3
      strictures (1.85%) in the Bricker group and 5 strictures (4.46%) in the Wallace
      group. There was no statistically significant difference between the stricture
      rate in these 2 groups (p = 0.21). Stricture rates for patients undergoing
      neoadjuvant or adjuvant radiation were not statistically significant from the
      patients with no adjuvant therapy. CONCLUSIONS: Overall the stricture rate for
      ureterointestinal anastomosis was 2.92%. There was no difference in stricture
      rate between the 2 types of ureterointestinal anastomosis.

PMID- 16600753
TI  - Urethral pressure profile following orthotopic neobladder: differences between
      nerve sparing and standard radical cystectomy techniques.
AB  - PURPOSE: Some authors reported that adopting a nerve sparing technique during
      radical cystoprostatectomy improves the continence outcome of orthotopic
      diversion in patients with invasive bladder carcinoma. We urodynamically
      evaluated the effect of nerve sparing cystoprostatectomy on external urethral
      sphincteric function. MATERIALS AND METHODS: A total of 30 consecutive male
      patients who underwent nerve sparing cystoprostatectomy and ileal neobladder (NS
      group) were compared to a control group of 30 patients who underwent a similar
      procedure but without nerve sparing (non-NS group). Continence status was
      thoroughly clinically evaluated in parallel to erectile function in both groups.
      The urethral sphincteric mechanism was evaluated with urethral pressure
      profilometry in different positions. RESULTS: Better urethral pressure profile
      parameters were found in patients in the NS group. Significantly longer
      functional urethral length (34.8 mm) was detected in NS group than in the non-NS
      group (30.1 mm). Moreover, the maximum urethral pressure was higher in the NS
      group but not to a statistically significant level. In the NS group there were no
      statistically significant differences between potent and impotent subgroups
      regarding the continence rate or urethral pressure parameters. CONCLUSIONS: There
      is urodynamic evidence that the nerve sparing technique improved urethral
      sphincteric function and, consequently, the continence rate. The denervated, most
      proximal part of the urethra in non-NS cases with lack of contraction and,
      therefore, any pressure, is a possible explanation for the difference in UPP.

PMID- 16600755
TI  - Pelvic organ support and prevalence by Pelvic Organ Prolapse-Quantification (POP
      Q) in Korean women.
AB  - PURPOSE: We evaluated pelvic organ support and the prevalence of pelvic organ
      prolapse in Korean women using the Pelvic Organ Prolapse-Quantification system as
      the assessment tool. MATERIALS AND METHODS: The study population consisted of 713
      women 18 to 72 years old who were seen for annual Papanicolaou testing and pelvic
      examinations. Pregnant patients and patients who had delivered within the
      previous 6 weeks were not recruited. All pelvic examinations were performed by a
      single examiner. The patient was examined in the dorsal lithotomy position in a
      pelvic examination chair positioned at a 15-degree angle. All 9 measurements
      except total vaginal length were taken with the patient performing the maximal
      Valsalva maneuver. RESULTS: Mean patient age was 41.6 years (range 18 to 72),
      mean weight +/- SD was 55.8 +/- 7.4 kg (range 40 to 83), mean height was 158.7 +/
      5.4 cm (range 138 to 177), mean body mass index was 22.3 +/- 8.1 kg/m2 (range
      15.7 to 32) and median parity was 2 (range 0 to 6). Mean scores for the position
      of the cervix and posterior fornix, and total vaginal length were -5.0, -6.6 and
      7.0 cm, respectively. In the 713 women with a uterus the incidence of anterior
      vaginal, uterine and posterior vaginal prolapse was 27.6%, 2.0% and 25.4%,
      respectively. The overall distribution of pelvic organ prolapse quantification
      system stage was stages 0 to 4 in 68.3%, 19.9%, 11.2%, 0.6% and 0.0% of patients,
      respectively. CONCLUSIONS: Vaginal size in Korean women differs from that in
      Western women. The prevalence of any degree of prolapse was approximately 31.7%.
      Korean women were at relatively higher risk for anterior and posterior vaginal
      prolapse than for uterine prolapse.

PMID- 16600756
TI  - Nerve growth factor and prostaglandins in the urine of female patients with
      overactive bladder.
AB  - PURPOSE: NGF and PGs in the bladder can be affected by pathological changes in
      the bladder and these changes can be detected in urine. We investigated changes
      in urinary NGF and PGs in women with OAB. MATERIALS AND METHODS: The study groups
      included 65 women with OAB and 20 without bladder symptoms who served as
      controls. Evaluation included patient history, urinalysis, a voiding diary and
      urodynamic studies. Urine samples were collected. NGF, PGE2, PGF2alpha and PGI2
      were measured using enzyme-linked immunosorbent assay and compared between the
      groups. In addition, correlations between urinary NGF and PG, and urodynamic
      parameters in patients with OAB were examined. RESULTS: Urinary NGF, PGE2 and
      PGF2alpha were significantly increased in patients with OAB compared with
      controls (p <0.05). However, urinary PGI2 was not different between controls and
      patients with OAB. In patients with OAB urinary PGE2 positively correlated with
      volume at first desire to void and maximum cystometric capacity (p <0.05).
      Urinary NGF, PGF2alpha and PGI2 did not correlate with urodynamic parameters in
      patients with OAB. CONCLUSIONS: NGF and PGs have important roles in the
      development of OAB symptoms in female patients. Urinary levels of these factors
      may be used as markers to evaluate OAB symptoms.

PMID- 16600758
TI  - The impact of detrusor overactivity on bladder function in younger and older
      women.
AB  - PURPOSE: We examined the relationship of DO and aging, and bladder function in
      female volunteers. MATERIALS AND METHODS: We recruited 85 cognitively competent,
      fully functional female volunteers who were 22 to 90 years old (median age 54)
      with and without symptoms suggestive of DO. Comprehensive assessment included a
      bladder diary, uroflowmetry and videourodynamics. We examined predefined
      urodynamic and diary variables for associations with DO and age, summarizing
      results in the 3 subgroups no DO, intermediate DO and clinically relevant DO.
      RESULTS: Compared to women without DO those with DO showed a decrease in maximum
      cystometric capacity (558 vs 448 ml), mean daytime voided volume (260 vs 175 ml)
      and volume at strong desire to void (363 vs 283 ml) but an increase in maximum
      isovolumetric pressure (41 vs 64 cm H2O) and maximum detrusor pressure during
      involuntary contraction (intermediate and relevant DO 22 and 37 cm H2O,
      respectively). The positive association between increased detrusor contraction
      strength and DO was present at younger ages but absent in older subjects. Maximum
      urethral closure pressure and detrusor contraction strength decreased
      significantly with age. CONCLUSIONS: From young adulthood to old age DO appears
      to affect bladder function parameters. It is associated with decreased bladder
      capacity and increased bladder sensation. Moreover, in younger adults DO is also
      associated with increased detrusor contraction strength, which is an association
      not seen in older individuals. This age associated loss of muscle function may be
      related to sarcopenia, implying that different treatments may be appropriate in
      older adults.

PMID- 16600760
TI  - Lower urinary tract dysfunction in ambulatory patients with incomplete spinal
      cord injury.
AB  - PURPOSE: We evaluated urinary tract dysfunction in individuals with spinal injury
      who remained able to ambulate. We observed changes with time in urological
      management. MATERIALS AND METHODS: All patients attending outpatient clinics with
      traumatic, incomplete (American Spinal Injury Association grades D and E) spinal
      cord injury during a 2-year period were identified. All patients had their
      hospital notes reviewed retrospectively and salient urological data extracted.
      RESULTS: A total of 43 men and 21 women were identified during this period. Mean
      age was 46 years (range 18 to 70). Mean followup was 7 years (range 1 to 18). At
      the time of inpatient discharge 40 of the 64 patients (62.5%) could void
      spontaneously, 20 required CSIC and 4 had a suprapubic catheter. In 19 of these
      40 patients (47.5%) who had been initially assessed as having a bladder that was
      safe to void spontaneously the condition deteriorated, such that CSIC was
      required. Conversely 5 of 20 patients (25%) who initially required CSIC improved,
      such that it became redundant. At last followup 68.7% of the patients had
      abnormal urodynamics and 24 of the 64 (37.5%) required a change in urological
      management despite no appreciably detectable neurological change. CONCLUSIONS:
      Despite relatively near total neurological recovery patients with incomplete SCI
      have neuropathic bladder unless proved otherwise. Salient deterioration in
      bladder dysfunction is not uncommon. Regular urological monitoring and
      appropriate treatment changes are required in the long term.

PMID- 16600762
TI  - The long-term results of pubovaginal sling surgery using acellular cross-linked
      porcine dermis in the treatment of urodynamic stress incontinence.
AB  - PURPOSE: Acellular cross-linked porcine dermis is a potential substitute for
      rectus fascia as a sling material with the advantage of decreased morbidity.
      However, the long-term efficacy is unknown. We compared the 3-year efficacy of PD
      vs autologous rectus fascia as a sling material for pubovaginal sling surgery in
      the treatment of urodynamic stress incontinence. MATERIALS AND METHODS: Between
      July 2000 and December 2001 a total of 101 consecutive, nonrandomized patients
      with USI underwent a PD (51) or RF (50) sling procedure. Patients were assessed
      at 6 weeks, and at 3, 6 and 12 months postoperatively. Urodynamic study was
      repeated in cases of treatment failure. A detailed survey questionnaire was
      mailed to all patients at least 36 months after surgery and all responders were
      then retested by telephone interview by a blinded assessor. The primary outcome
      measure was patient perceived success rate (cured or improved) at least 36 months
      after PVS. Secondary outcome measures were patient satisfaction 36 months after
      surgery, durability of success with time and reoperation rate. RESULTS: Complete
      data were available on 94 patients (48 treated with PD and 46 treated with RF
      sling). The groups were well matched for age, leak point pressure, prior
      incontinence surgery and urge symptoms. Pubovaginal sling was successful (cured
      or improved) in 37 (80.4%) patients treated with RF but in only 26 (54%) patients
      treated with PD 36 months after surgery (Fisher's exact test p = 0.009; 95% CI
      8.03, 44.4). Treatment failure occurred by 9 months after RF and by 24 months
      after PD sling procedure. Repeat urodynamic study showed USI to be the cause of
      treatment failure in 18 (37.5%) of 20 patients treated with PD but in only 3
      (6.5%) of 8 patients treated with RF. CONCLUSIONS: We have shown that use of the
      PD sling, although reducing early morbidity, results in a significantly inferior
      long-term cure rate in comparison to the RF sling. Therefore, acellular cross
      linked porcine dermis should not be used as a substitute for rectus fascia.

PMID- 16600764
TI  - Spiral sling salvage anti-incontinence surgery in female patients with a
      nonfunctional urethra: technique and initial results.
AB  - PURPOSE: Female patients with severe urethral incompetence are a unique surgical
      challenge. Urethral closure and continent diversion are often the next step in
      the treatment of these patients. We present a technique that provides
      circumferential coaptation of the urethra as a salvage procedure in this severe
      subset of patients. MATERIALS AND METHODS: We prospectively evaluated 47 patients
      who had a spiral sling. A 1 x 15 cm piece of soft polypropylene mesh was prepared
      with a zero polyglactin suture applied at each end. A clamp was used to pass the
      mesh between the urethra and pubis. The ends of the mesh were crossed at the
      ventral aspect of the urethra, creating a complete circle around the urethra. The
      sutures were transferred to the suprapubic area and tied without tension. The
      surgical outcome was determined by patient self-assessment, including symptom,
      bother and quality of life questionnaires. RESULTS: Mean patient age was 59
      years. At presentation patients had undergone a mean of 2.6 incontinence
      procedures and wore a mean of 6 pads daily. Mean daily pad use decreased to 0.9
      (p <0.005). Preoperatively mean SUI symptom severity and bother scores were 2.8
      and 2.9, respectively, on a scale of 0--none to 3--severe. Postoperatively these
      values decreased to 0.6 and 0.4, respectively (each p <0.005). There was a mean
      87% overall improvement in symptoms. CONCLUSIONS: The spiral sling is an
      effective salvage transvaginal procedure that may be considered in a small subset
      of female patients with a nonfunctional urethra as a last resort before urethral
      closure procedures.

PMID- 16600766
TI  - Erectile function profiles in men with Peyronie's disease.
AB  - PURPOSE: In this study we investigated the erectile function status of men
      presenting with Peyronie's disease. MATERIALS AND METHODS: Demographics of
      patients regarding age, duration of PD, nature of deformity and comorbidities
      were compared between the patients with PD, with and without erectile
      dysfunction. Patients with erectile dysfunction underwent dynamic infusion
      cavernosometry/cavernosography. The hemodynamic profile of patients presenting
      with combined PD and ED were analyzed and compared between those with onset of ED
      before and after diagnosis of PD. RESULTS: Of the 222 patients 78 had ED (35%) by
      self-report at presentation. The mean age of patients with PD and ED was 52 +/-
      22 years old. Hypertension (71.5%), hyperlipidemia (60.4%) and smoking (49.2%)
      were the leading comorbidities in the entire group. Statistically significant
      differences were found between the groups with and without ED for hypertension (p
      = 0.02) and cigarette smoking (p = 0.009). Of 222 patients 45 (20%) had ED that
      predated PD onset (group 1) and 33 (15%) had ED that postdated the onset of PD
      (group 2). DICC showed normal hemodynamics in 14 of 78 patients (18%),
      arteriogenic insufficiency in 50 (64%) and corporoveno-occlusive dysfunction in
      16 (20%). CVOD was evenly distributed between groups 1 and 2, whereas
      arteriogenic ED was significantly higher in group 1 (82%). Site specific leak was
      seen in 4 of 33 (12%), all group 2 patients. CONCLUSIONS: Patients in whom ED
      postdates the onset of PD are more likely to have normal erectile hemodynamics.
      Site specific leak is an uncommon contributor to PD and is seen only in the
      patients with PD in whom ED postdated PD onset. The leading vascular etiology of
      ED in PD is arteriogenic in older patients and those with greater associated
      comorbidities.

PMID- 16600768
TI  - Effect of nonsteroidal anti-inflammatory drug use on the incidence of erectile
      dysfunction.
AB  - PURPOSE: We estimated the effect of nonsteroidal anti-inflammatory drug use on
      the incidence of erectile dysfunction. MATERIALS AND METHODS: The target
      population consisted of men 50, 60 or 70 years old residing in the study area in
      Finland in 1994. Questionnaires were mailed to 3,143 men in 1994 and to 2,864 men
      5 years later. The followup sample consisted of 1,683 men who responded to
      baseline and followup questionnaires. We estimated the effect of NSAIDs on the
      incidence of ED in men free from moderate or complete ED at baseline (in 1,126).
      ED was assessed by 2 questions on subject ability to achieve or maintain an
      erection sufficient for intercourse. Confounding was assessed by stratification
      and by adjustment in multivariate Poisson regression model. RESULTS: The
      incidence of ED was 93 cases per 1,000 person-years in men who used and 35 in
      those who did not use NSAIDs. Among men with arthritis, the most common
      indication for NSAID use, ED incidence was 97 cases per 1,000 in those using and
      52 in men who did not use NSAIDs. Compared with men who did not use NSAIDs and
      were free from arthritis, the relative risk of ED after controlling for the
      effects of age, smoking, and other medical conditions and medications was higher
      in men who used NSAIDs but were free of arthritis (IDR 2.0, 95% CI 1.2-3.5) and
      in those who used NSAIDs and had arthritis (IDR 1.9, 95% CI 1.2-3.1). The
      relative risk was only somewhat higher in men who had arthritis but did not use
      NSAIDs (IDR 1.3, 95% CI 0.9-1.8). CONCLUSIONS: The use of nonsteroidal anti
      inflammatory drugs increases the risk of ED and the effect is independent of
      indication.

PMID- 16600770
TI  - Impact on sexual function of holmium laser enucleation versus transurethral
      resection of the prostate: results of a prospective, 2-center, randomized trial.
AB  - PURPOSE: We compared the impact of HoLEP and TURP on sexual function. MATERIALS
      AND METHODS: Between January 2002 and January 2003, 120 patients with a mean age
      +/- SD of 65.2 +/- 7.1 years who had benign prostatic hyperplasia were enrolled
      in this 2-center, prospective, randomized study. A total of 60 patients with a
      mean age of 65.25 +/- 6.9 years underwent HoLEP (group 1) and 60 with a mean age
      of 64.18 +/- 7.2 years underwent TURP (group 2). Patients were assessed before
      surgery, and at 12 and 24-month followup visits. Subjective symptoms were scored
      by the International Prostate Symptom Score, the International Prostate Symptom
      Score quality of life question, IIEF, 10 nonvalidated general assessment
      questions, physical examination, serum prostate specific antigen and transrectal
      ultrasonography. RESULTS: A total of 32 patients (53.3%) in group 1 and 31
      (51.6%) in group 2 reported various degrees of erectile dysfunction before
      surgery according to the IIEF-EF score. Differences between preoperative and
      postoperative orgasmic domain scores in each group were significant (p <0.001). A
      slight but not significant increase in the mean IIEF-EF domain score was reported
      in each group at postoperative assessments without any difference between the 2
      surgical approaches. According to general assessment question analysis the
      prevalence of subjectively reported postoperative retrograde ejaculation was
      significantly higher than at baseline assessment in the 2 groups with no
      differences between the 2 surgical procedures. CONCLUSIONS: TURP and HoLEP
      significantly lowered the IIEF orgasmic function domain with no differences
      between techniques. This was caused by retrograde ejaculation. Marginal,
      nonsignificant erectile function improvement was reported after surgery in the 2
      groups.

PMID- 16600771
TI  - Open testicular biopsy without a surgical assistant using a scrotal Rumel
      tourniquet.
AB  - PURPOSE: The main current indication for open testicular biopsy is the extraction
      of sperm cells for intracytoplasmic sperm injection in patients with azoospermia.
      Usually the surgical assistant or operator holds the testicle with the
      nondominant hand throughout the operation. We propose using a scrotal device in
      the shape of a Rumel tourniquet to maintain the testicle fixed and tight against
      the scrotal wall all the time with no need to be held by the hand. MATERIALS AND
      METHODS: The Rumel tourniquet is made of a Penrose-type rubber drain and a piece
      of plastic tube. It is placed at the base of the scrotum to include the 2
      testicles, while tension is adjusted until the skin becomes tense and the scrotal
      wall is held tightly against the testicles. Placing the eyelid retractor is
      unnecessary since the various scrotal wall layers become spontaneously separated.
      RESULTS: We have used this device in 20 consecutive testicular biopsies in
      patients with obstructive azoospermia and for histopathological diagnosis. It was
      useful in all cases. No device related complications were observed. CONCLUSIONS:
      This straightforward scrotal device simplifies the procedure since no surgical
      assistant is required, the surgeon can use 2 hands during the operation and
      testicular biopsy is achievable through a small incision.

PMID- 16600772
TI  - Unequal use of new technologies by race: the use of new prostate surgeries
      (transurethral needle ablation, transurethral microwave therapy and laser) among
      elderly Medicare beneficiaries.
AB  - PURPOSE: We compared the availability and use of transurethral microwave therapy,
      transurethral needle ablation, contact or noncontact laser therapy and
      transurethral resection of the prostate among elderly black and white Medicare
      beneficiaries. MATERIALS AND METHODS: We examined 100% Medicare Inpatient,
      Outpatient, Carrier and Denominator files of men 65 years old or older who
      underwent these procedures in 1999 through 2001. White-to-black race rate ratios
      for each procedure were computed for the entire United States, as well as for a
      restricted set of counties in which procedures were available to black
      beneficiaries. RESULTS: A total of 170,067 TURP, 16,953 TUMT, 5,353 TUNA and
      12,134 Laser procedures were performed during 3 years. Nationally there was only
      a 3% difference in the age adjusted TURP rates between white and black men (6.13
      and 5.94 per 1,000 person-years, respectively). However, the age adjusted rates
      for TUMT and TUNA among white men were about twice those among black men (0.63 vs
      0.31 and 0.20 vs 0.10 per 1,000 person-years, respectively). Laser rates were 17%
      higher among white men than among black men (0.44 vs 0.38 per 1,000 person
      years). Large geographic variation existed in the new procedure rates. Negative
      binomial regression analysis confirmed the national findings in those counties in
      which the procedures were available to black men. Adjusted white-to-black rate
      ratios were 1.96 (95% CI 1.70-2.25) for TUMT, 2.33 (95% CI 1.87-2.90) for TUNA
      and 1.36 (95% CI 1.16-1.59) for Laser. CONCLUSIONS: After controlling for
      availability, elderly black Medicare beneficiaries were less likely to undergo
      the new BPH procedures than white beneficiaries, while the usage difference for
      TURP remained small.

PMID- 16600774
TI  - Prostate cancer on the Internet--information or misinformation?
AB  - PURPOSE: We assessed the quality of information available to patients on prostate
      cancer on the Internet. MATERIALS AND METHODS: The search engine Webcrawler was
      used with the search term "prostate cancer" to generate a list of 75 websites
      which were reviewed for currency, disclosure, attribution, interactivity and
      content. A rating tool was designed including 50 elements considered essential
      for a comprehensive review of prostate cancer, and each website was judged for
      degree of coverage and accuracy (each rated on a scale of 1 to 3) of information
      for each element. RESULTS: Of the 75 sites 39 contained information about
      prostate cancer. Only 9 sites indicated a date of last update within 6 months.
      References were rarely given (in 5) and a disclaimer was provided on less than
      half of the sites (18). The sites covered a mean of 24 elements (range 6 to 43)
      with a mean coverage rating of 1.0 to 2.6 (1.8 overall). Of 943 elements covered
      on 39 sites, 94% were completely correct, 5% were mostly correct and 1% was
      mostly incorrect. CONCLUSIONS: The information on the Internet is of sufficient
      quality to aid in patient decision making. However, there are numerous
      shortcomings especially related to currency, disclosure and attribution. Degree
      of coverage is highly variable and there is a deficiency in balance of evidence
      found on many sites. The urologist needs to be aware of such shortcomings when
      counseling patients on prostate cancer.

PMID- 16600776
TI  - Medical knowledge: the importance of faculty involvement and curriculum in
      graduate medical education.
AB  - PURPOSE: The Accreditation Council for Graduate Medical Education requires that
      each residency program must demonstrate and document actual accomplishments
      through objective measures. At University of Washington we identified
      deficiencies in resident medical knowledge and designed interventions that would
      assist in improving resident AUA IS scores, using this as a metric to document
      the outcomes. MATERIALS AND METHODS: In 2001 the University of Washington
      syllabus and faculty precepted chapter review sessions were formally established.
      The national AUA IS was used as an objective standardized examination to
      determine an annual group percentile score. RESULTS: We noted a gradual and
      consistent increase in the average percentile group score on the national annual
      AUA IS examinations of our residents. A generalized estimating equation model
      demonstrated a significant difference between pre-intervention and post
      intervention average percentile resident AUA IS scores (p <0.001). Average
      resident percentile rankings in 2001 to 2004 were 25.6 points higher than the
      average rankings of residents tested in 1997 to 2000. CONCLUSIONS: We developed
      and evaluated a cohesive core curriculum designed to improve resident knowledge
      in urology, as measured by the AUA IS metric. With the active participation of
      faculty the curriculum enhanced resident education.

PMID- 16600777
TI  - Medical malpractice liability in clinical urology: a survey of practicing
      urologists.
AB  - PURPOSE: The current medical malpractice environment is in crisis. Costs
      associated with litigation as well as medical malpractice insurance premiums have
      increased during the last decade. In fact as of March 2004 the American Medical
      Association has identified 19 states as crisis states. We investigated the way in
      which the medical malpractice environment has affected urologists and the manner
      in which they practice medicine. MATERIALS AND METHODS: A survey of 31 questions
      was electronically mailed to the American Urological Association's database of
      practicing urologists in the United States. Data were gathered on each
      urologist's malpractice history as well as their clinical practice. A total of
      5,919 surveys were mailed and 683 (12%) were returned. Urologists from 47 states
      responded. RESULTS: The mean medical malpractice premium in 2003 was 30,665
      dollars (median 22,500 dollars, range 6,000 dollars to 120,000 dollars). Of
      responding urologists 63% report being named in a medical malpractice lawsuit a
      mean of 2.1 times. Mean length of time practicing urology was 19 years. Of the
      lawsuits 28% involved urological oncology, 12% involved endourology and 10%
      involved female urology. All other urological specialties individually generated
      less than 10% of the lawsuits. In only 3.5% of the cases was the patient
      successful at trial, compared to 13.2% of the cases where the urologist was
      successful at trial. The case was dropped or dismissed without financial
      settlement 46.9% of the time. However, 36.3% of the time the case was settled
      with a pretrial financial settlement. The mean amount awarded to a patient at
      trial was 213,855 dollars (median 100,000 dollars, range 2,400 dollars to
      1,000,000 dollars). When a patient was awarded pain and suffering at trial, the
      mean amount awarded was 270,000 dollars (median 85,000 dollars, range 30,000
      dollars to 900,000 dollars). The mean amount given to the patient as pretrial
      settlement was 196,706 dollars (median 70,000 dollars, range 1,500 dollars to
      5,000,000). The mean time a urologist spent defending their first lawsuit was
      21.8 days. Given the current medical malpractice environment, 58% of responding
      urologists are considering referring difficult cases, 60% are considering
      limiting the scope of their practice, 26% are considering changing the state in
      which they practice and 41% are considering leaving the practice of medicine.
      CONCLUSIONS: Our experience has shown that the medical malpractice crisis has had
      a profound and real effect on the urological community. When the data are
      stratified according to those urologists who practice in a crisis state, we
      consistently see a pattern whereby the crisis state urologists are carrying a
      larger proportion of the malpractice burden. Most concerning is how the
      malpractice environment has changed the way in which urologists approach their
      practice. A larger percentage of urologists from crisis states are reporting that
      they are considering limiting the scope of their practice, moving their practice
      to a state with a more favorable malpractice environment and considering leaving
      the practice of urology altogether. Clearly the urologist is not immune from the
      current malpractice environment.

PMID- 16600778
TI  - Highlights from the combined Society of Urodynamics and Female Urology and
      International Society of Pelvic Neuromodulation annual meeting.

PMID- 16600779
TI  - Gonadoblastoma and Turner syndrome.
AB  - PURPOSE: The presence of a Y chromosome in the extrascrotal gonad of patients
      with intersex disorders has been associated with a high risk of GB and,
      potentially, GCT. Recently, modern sophisticated genotyping has revealed a
      subgroup of TS cases with a mosaic karyotype expressing a Y chromosome. We sought
      to evaluate this group of patients and address their risk of gonadoblastoma.
      MATERIALS AND METHODS: We reviewed the records and genotyping of all females
      newly diagnosed with TS between 1990 and 2002 at Children's Hospital in Denver.
      All patients with TS and Y chromosome mosaicism underwent gonadectomy, and the
      specimens were evaluated for the presence of gonadoblastoma on histological
      analysis and to identify Y chromosome on genotyping. RESULTS: A total of 192
      girls with a clinical diagnosis of TS were identified between January 1990 and
      December 2002. Seven records were unavailable and 19 patients did not have
      karyotypic analyses available in the hospital charts. Of the remaining 166
      patients 67 exhibited mosaic cell lines, of whom 8 had 45,X0/46,XY mosaic pattern
      and 59 had mosaic patterns without Y chromosomal elements. All 8 patients with Y
      mosaicism underwent uneventful laparoscopic gonadectomy on an outpatient basis.
      One patient observed to have bilateral dysgenetic gonads after gonadectomy was
      excluded from the study. Gonadoblastoma (bilateral 2 patients, unilateral 1) was
      detected in 3 of 7 patients (43%) with Y mosaicism. CONCLUSIONS: In our series
      4.8% of evaluable patients with TS carried a 45,X0/46,XY karyotype.
      Gonadoblastoma can be evident even at an early age in streak gonads with Y
      mosaicism and may be bilateral. We recommend prophylactic laparoscopic
      gonadectomy of streak gonads in patients with TS who carry a Y mosaic genotype,
      because fertility is not an issue, surgical morbidity is minor and there may be a
      high potential for malignant transformation of gonadoblastomas in this
      population.

PMID- 16600780
TI  - Safety of gentamicin bladder irrigations in complex urological cases.
AB  - PURPOSE: Recurrent urinary tract infections are common in complex pediatric
      urological cases, particularly those requiring clean intermittent
      catheterization. At our institution gentamicin bladder irrigations have been used
      for antimicrobial prophylaxis and to treat symptomatic bacteriuria, particularly
      when the infection does not involve the upper urinary tract. The purpose of this
      study was to assess the safety of this therapy. MATERIALS AND METHODS: A
      retrospective study was performed of all children treated with gentamicin bladder
      irrigations from 1999 to 2004. The dose was 14 mg gentamicin in 30 ml saline
      instilled via catheter once or twice daily. Serum creatinine and random
      gentamicin levels were obtained according to a protocol based on risk of
      gentamicin toxicity. Patient demographics, laboratory results and outcomes were
      abstracted from the medical records. RESULTS: A total of 80 patients (38 males
      and 42 females) were identified. Median patient age was 10 years and median
      duration of treatment was 90 days. No patient had detectable serum gentamicin
      levels greater than 0.4 mg/dl. Small increases in serum creatinine were seen in 3
      patients, all of whom had chronic renal insufficiency. A total of 21 patients
      (26%) had breakthrough UTIs, of which 5 (24%) were gentamicin resistant. No
      adverse events were documented. CONCLUSIONS: Gentamicin bladder irrigations are a
      helpful adjunct in the management of complex pediatric urological cases involving
      recurrent symptomatic bacteriuria. We no longer require intensive laboratory
      monitoring of low risk patients at our institution.

PMID- 16600781
TI  - Transverse myelitis in children: long-term urological outcomes.
AB  - PURPOSE: Urological complications are well documented in patients with traumatic
      spinal cord injury. We examined the long-term urological outcomes in a large
      population of children affected by transverse myelitis. MATERIALS AND METHODS: We
      retrospectively reviewed the medical history, imaging studies and urodynamic
      findings in 22 children with transverse myelitis. Age at disease onset ranged
      from 3 months to 18 years (average 8.8 years). RESULTS: At a mean followup of 7.1
      years 19 patients (86%) had persistent bladder dysfunction and 17 (77%) had
      persistent bowel dysfunction. Initial evaluation at least 1 month after disease
      onset revealed detrusor overactivity in 59% of patients, detrusor external
      sphincter dyssynergia in 41%, low compliance in 47% and detrusor leak point
      pressure greater than 40 cm water in 12%. Functional motor recovery and absence
      of lower extremity spasticity did not reflect normal urodynamic findings. Of the
      19 patients with imaging available for review 5 (26%) had upper tract changes.
      One patient had development of chronic renal insufficiency. Low compliance (p =
      0.02) and upper tract changes (p = 0.1) were more frequent in patients who
      started clean intermittent catheterization more than 2 years after disease onset.
      CONCLUSIONS: Persistent bowel and bladder dysfunction is common in transverse
      myelitis. Urodynamic abnormalities may be present despite normal neurological
      examination and absence of urinary symptoms. All pediatric patients with
      transverse myelitis require baseline renal ultrasound and urodynamic evaluation
      to guide treatment. Early institution of clean intermittent catheterization
      appears to preserve bladder compliance and decrease upper tract disease, and
      should be instituted at disease onset.

PMID- 16600783
TI  - An approach for using full thickness skin grafts for complex penile surgeries in
      children.
AB  - PURPOSE: Many problems in pediatric urology derive from a paucity of penile skin
      resulting from prior surgical interventions. While hypospadias surgery is most
      often responsible for creating this problem, excessive circumcision also can
      leave a patient with too little skin to cover the penis. To our knowledge we
      describe the first series of pediatric patients in whom FTSGs were used in a
      variety of difficult circumstances where penile skin was lacking. MATERIALS AND
      METHODS: We retrospectively studied a cohort of 11 children 2 to 13 years old who
      underwent urethral repair and adjunctive skin grafting due to circumcision
      injuries (4 patients), traumatic urethral injury (1) or congenital
      lymphangiectasis (1), or for congenital hypospadias with previous failed surgery
      (5). In our patients available penile skin was used to reconstruct the urethra,
      while full thickness inguinal skin grafts were fashioned to resurface the denuded
      penis following reconstruction. RESULTS: All patients underwent successful
      reconstruction and grafting. There were no intraoperative complications. There
      was 100% take of the grafts. Average followup was 23 months (range 3 weeks to 8.6
      years). One patient had slight chordee at 6 years postoperatively, and 1 had
      development of a urethrocutaneous fistula at 8.6 years. All patients reported
      normal caliber urinary streams. CONCLUSIONS: Use of full thickness inguinal skin
      grafts to resurface the penis provided patients with an esthetically acceptable
      result, and where necessary allowed penile skin to be used for urethroplasty.
      This technique is useful and justifies consideration in appropriately selected
      patients.

PMID- 16600785
TI  - Interim outcome of the single stage dorsal inlay skin graft for complex
      hypospadias reoperations.
AB  - PURPOSE: Despite high success rates for primary hypospadias repair, some cases
      require multiple procedures for ultimate reconstruction. We report our experience
      with single stage dorsal inlay urethroplasty using skin grafts for complex
      reoperations. MATERIALS AND METHODS: A total of 31 patients (mean age 13.8 years)
      with failed previous hypospadias surgery were included in the study. Indications
      included fistulas, strictures, diverticula and repair breakdown. The urethral
      plate had been removed or was severely scarred in all patients. A free penile or
      groin skin graft was sutured and quilted to the corpora cavernosa, guaranteeing
      sufficient blood supply. The neourethra was tubularized and covered with a tunica
      vaginalis or dartos flap, followed by glanuloplasty. Outcome analysis included
      urethrograms, urethral ultrasound and flow measurements. RESULTS: Foreskin was
      used in 15 cases, penile skin in 12 and inguinal skin in 4. Average graft length
      was 3.92 cm. A total of 20 patients required glanuloplasty with a skin graft
      extended to the tip of the glans. After a mean followup of 30.71 months 5
      patients underwent redo surgery, for a complication rate of 16.1%. Urethral
      stricture of the proximal anastomosis was the most frequent finding. CONCLUSIONS:
      This single stage approach using dorsal skin grafts is a reliable method to
      create a substitute urethral plate for tubularization. Complication rates are
      equivalent to those of staged procedures. Foreskin should be used as a graft
      donor site to optimize the outcome if available. This approach represents a safe
      option for reoperations even if the urethral plate or midline penile skin is
      grossly scarred.

PMID- 16600787
TI  - Long-term surgical results and patient satisfaction with male
      pseudohermaphroditism or true hermaphroditism: a cohort of 63 patients.
AB  - PURPOSE: To improve treatment policy, we retrospectively evaluated the results of
      early corrective genital surgery in 63 sexually ambiguous patients 14 to 38 years
      old. MATERIALS AND METHODS: We analyzed all records classified under male
      pseudohermaphroditism and true hermaphroditism. Anatomical and functional results
      and data on self-reported satisfaction were recorded by the managing physician at
      the last routine followup visit. RESULTS: A total of 38 patients were raised
      female and 25 were raised male. Basal procedures for external genital
      reconstruction were initiated shortly after birth, when gender was assigned.
      Complementary surgical procedures were usually required later. In both sexes
      there was a significant negative correlation between the number of basal, but not
      complementary, procedures required and year of birth, due to the adoption of 1
      stage procedures in the early 1980s. Most patients with gonadal dysgenesis were
      raised as females and menstruated under treatment but breast development was
      abnormal in 30%. Spontaneous puberty was observed in true hermaphrodites raised
      as either sex. In females with partial androgen insensitivity the main problem
      was shortness of the vagina. Amenorrhea and infertility often led to transient
      distress. In males results were poor due to intractable micropenis and minimal
      virilization. Results were good in 5alpha-reductase deficiency. CONCLUSIONS:
      Results of intersex surgery have clearly improved with time, and apart from a
      patient with 5alpha-reductase deficiency who underwent a successful sex change,
      no patient expressed dissatisfaction with sex of rearing. However, in the absence
      of an in-depth psychological survey, these optimistic conclusions are valid only
      in the settings of our study.

PMID- 16600788
TI  - Resolution of diurnal incontinence and nocturnal enuresis after
      adenotonsillectomy in children.
AB  - PURPOSE: Adenotonsillar hyperplasia causes upper airway obstruction, leading to
      obstructive sleep apnea. We reviewed the incidence of nocturnal enuresis in a
      population of children with adenotonsillar hyperplasia. In addition, we
      investigated the rate of resolution or improvement in enuresis following surgery
      for relief of adenotonsillar hyperplasia. MATERIALS AND METHODS: We studied 86
      consecutive prepubertal children, 46 boys and 40 girls, who underwent
      adenotonsillectomy. Severity of adenotonsillar obstruction was graded on a scale
      of 1 to 4. A questionnaire regarding voiding problems, including nocturnal
      enuresis, voids per day and daytime enuresis episodes, was filled out
      preoperatively and postoperatively by the patients and their parents. RESULTS:
      Among the 86 patients who underwent adenotonsillectomy 36 (42%) had nocturnal
      enuresis. In patients with nocturnal enuresis the number of episodes was
      significantly less after adenotonsillectomy. Overall, 12 patients (33%) had
      complete resolution, 11 (31%) had significant improvement and 13 (36%) showed no
      change. In addition, we noted a significant decrease in daytime enuresis episodes
      and voids per day. CONCLUSIONS: Children with upper airway obstruction have a
      high rate of nocturnal enuresis that improves at twice the anticipated rate after
      treatment of the airway obstruction. In addition, we observed that daytime
      voiding dysfunction improves in these patients.

PMID- 16600793
TI  - The impact of late presentation of posterior urethral valves on bladder and renal
      function.
AB  - PURPOSE: We retrospectively reviewed the records of patients with late
      presentation of PUVs, and compared bladder and renal function to that in patients
      with an early diagnosis of PUVs. MATERIALS AND METHODS: We retrospectively
      reviewed the charts of 36 males (mean age at diagnosis 8.8 years, range 5 to 14)
      with late presentation of PUVs who were treated at our institution between 1986
      and 2004. Of these patients 20 had undergone urodynamic evaluation during
      followup (mean age 10.65 years, range 5 to 23). We chose as controls 19 age
      matched children with PUVs who were diagnosed and treated before age 5 years and
      underwent urodynamic evaluation during followup (mean age at urodynamic
      evaluation 8.52 years, range 6 to 15). Urodynamic parameters were compared
      between the 2 patient groups. Renal function in the late presenting cases was
      also compared to controls. RESULTS: The most common symptoms at presentation were
      diurnal enuresis (17 patients, 47.2%) poor stream (7, 19.4%) and urinary
      retention (5, 13.9%). Overall, urodynamic bladder abnormalities were detected in
      17 of 20 patients (85%), detrusor overactivity in 3 (15%), significant post-void
      residual in 9 (45%) and bladder capacity greater than expected for age in 9
      (45%). No significant difference in bladder capacity, compliance or post-void
      residual was demonstrated between the late presenting and control groups. Only
      detrusor overactivity was significantly lower in the late presenting group (p =
      0.013). After a mean followup of 67.03 months age specific creatinine levels were
      increased in 13 of 27 patients (48.1%), including 7 (25.9%) with ESRD. Renal
      function was significantly impaired in the late presenting group compared to
      controls (48.1% vs 13.7%, p = 0.001). CONCLUSIONS: We found a significantly lower
      rate of detrusor overactivity (15%) in patients with late presenting PUVs.
      Comparison of urodynamic parameters between the early and late presenting groups
      did not reveal any significant difference. This similar pattern of bladder
      dysfunction, independent of age at relief of obstruction, may indicate a common
      pathophysiological etiology for bladder dysfunction in all patients with PUVs.
      Also, renal function was significantly impaired in the late presenting group in
      this series.

PMID- 16600790
TI  - Single center experience with endoscopic management of vesicoureteral reflux in
      children.
AB  - PURPOSE: Dx/HA copolymer was approved by the Food and Drug Administration in 2001
      for the treatment of VUR in children. Published results have varied widely,
      prompting us to report our single center experience with 300 consecutive
      patients. MATERIALS AND METHODS: All patients undergoing Dx/HA injection (300
      children, median age 5.4 years) at our institution were eligible for this study.
      We examined several parameters to determine which variables influence the success
      of Dx/HA injection, including preoperative reflux grade, bladder diverticula,
      neurogenic bladder, ureteral duplication, perioperative urinary tract infection,
      dysfunctional voiding, laterality of reflux and amount of Dx/HA injected.
      RESULTS: A total of 225 patients (75%) underwent postoperative studies, and,
      thus, were eligible for study inclusion. Reflux was cured in 144 patients (64%)
      and improved in 44 (20%). A total of 20 patients had ureteral duplication
      anomalies. Cure rates in this subgroup were significantly decreased compared to
      nonduplicated cases (40% vs 66%). Injection in low grade (I to II) reflux was
      significantly more successful than in high grade (III to IV) reflux (72% vs 54%).
      A total of 10 patients (8.3%) with unilateral reflux had development of de novo
      contralateral reflux. Of the patients who failed initial injection 10 (4%)
      underwent repeat injection, of whom 5 (50%) were cured after the second
      injection. Two patients (0.9%) had development of temporary ureteral obstruction.
      CONCLUSIONS: We report a large short-term single center experience with
      endoscopically injected Dx/HA. Although our cure rate of 64% was less than
      published rates for open surgery, the minimal morbidity and low complication rate
      of endoscopic treatment make it an attractive first line therapy for patients
      with VUR. Longer followup is required to better evaluate this technique.

PMID- 16600795
TI  - Increased echogenicity as a predictor of poor renal function in children with
      grade 3 to 4 hydronephrosis.
AB  - PURPOSE: Prenatally diagnosed hydronephrosis is a common finding that often
      requires further radiological evaluation to determine whether it is associated
      with compromised renal function. We hypothesize that findings on postnatal renal
      sonography may help determine which patients require more extensive evaluation of
      renal function in the assessment for prenatal hydronephrosis. We show that
      increased renal parenchymal echogenicity on postnatal US is a strong predictor of
      compromised renal function. MATERIALS AND METHODS: A total of 97 patients
      diagnosed with prenatal hydronephrosis presented to our institution for
      furosemide (99m)technetium MAG3 renogram evaluation of renal function between
      January 2000 and December 2001. All patients had SFU grade 3 to 4 hydronephrosis
      noted on postnatal US before age 6 months. For these 97 patients (178 renal
      units) we correlated the degree of renal parenchymal echogenicity and parenchymal
      thinning on the first postnatal sonogram with the differential renal function as
      determined by furosemide MAG3 renography. RESULTS: Among 97 patients diagnosed
      with prenatal hydronephrosis 10 of 20 renal units (50%) with markedly increased
      echogenicity had severely decreased relative renal function of less than 10%,
      while 136 of 151 (90%) with normal echogenicity exhibited normal relative renal
      function of 40% or greater. Increased echogenicity on US yielded a sensitivity of
      100% and specificity of 99% for predicting relative renal function of 20% or
      greater. In predicting relative renal function of 40% or less sensitivity and
      specificity were 48% and 100%, respectively. CONCLUSIONS: Increased renal
      parenchymal echogenicity found on the first postnatal ultrasound can be used as a
      predictor of impaired relative renal function as measured on furosemide MAG3
      renogram.

PMID- 16600796
TI  - Sarcomatoid urothelial carcinoma of the renal pelvis.

PMID- 16600797
TI  - Expression of hypoxia inducible factor-1alpha and 2alpha in genetically distinct
      early renal cortical tumors.
AB  - PURPOSE: The role of the HIF class of transcription factors has been implicated
      to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over
      expression is a prominent feature of other renal cell carcinoma histological
      subtypes we characterized the expression of HIF-1alpha and HIF-2alpha in
      genetically distinct early renal cortical tumors. MATERIALS AND METHODS: Nascent
      renal tumors of distinct histology from patients with a hereditary renal tumor
      syndrome were characterized for HIF expression using high amplification
      immunohistochemistry. In addition, indirect immunofluorescence and confocal
      microscopy were used for subcellular localization of HIF-1alpha and 2alpha in
      clear cell renal carcinoma cells. RESULTS: Clear cell RCC tumors from patients
      with von Hippel-Lindau disease strongly expressed HIF-1alpha and HIF-2alpha (10
      of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with
      Birt-Hogg-Dube syndrome expressed predominantly HIF-2alpha with weaker HIF-1alpha
      expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1alpha
      expression was not seen in type I papillary tumors from patients with hereditary
      papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary
      tumors (6 of 12) expressed HIF-2alpha. CONCLUSIONS: Differential patterns of HIF
      1alpha and HIF-2alpha protein over expression were found among the 3 human kidney
      tumor types associated with multifocal hereditary kidney tumor syndromes.
      Consistent, simultaneous over expression of HIF-1alpha and HIF-2alpha appears to
      be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF
      2alpha expression was found in all 3 renal cortical tumor subtypes, suggesting a
      pivotal role in renal cortical tumorigenesis. Differential function of HIF-1alpha
      vs HIF-2alpha is suggested by the distinct subcellular localization pattern of
      HIF-1alpha and HIF-2alpha in clear cell renal carcinoma cells.

PMID- 16600798
TI  - Identification and validation of suitable endogenous reference genes for gene
      expression studies of human bladder cancer.
AB  - PURPOSE: Housekeeping genes as endogenous references are generally used for the
      relative quantification of target genes in gene profiling studies. To date that
      issue has not been sufficiently investigated in bladder cancer. From a panel of 9
      potential candidates we selected the most stable housekeeping genes for gene
      normalization in bladder cancer tissue. MATERIALS AND METHODS: Expression
      profiles of the 9 genes ACTB, ALAS1, G6PD, GAPD, HMBS, HPRT1, K-ALPHA-1, SDHA and
      TBP were established in matched malignant and nonmalignant tissue specimens from
      14 patients with bladder cancer. Quality assessment of isolated RNA was performed
      with a 2100 Bioanalyzer (Agilent Technologies, Palo Alto, California) and real
      time reverse transcriptase-polymerase chain reaction was performed with
      LightCycler. The software geNorm and NormFinder (Aarhus University, Aarhus,
      Denmark) were used to identify the most suitable reference genes. RESULTS: RNA
      was isolated with high purity and integrity. Candidate reference genes showed a
      broad range of between 20 and 34 polymerase chain reaction cycles. Expression did
      not depend on patient sex or tumor stage. GAPD, G6PD and HMBS showed significant
      differences in expression between malignant and nonmalignant pairs (at least p
      <0.04). Expression of the remaining genes did not differ between the matched
      pairs. SDHA and TBP were the most stably expressed genes, covering higher and
      lower expression levels. CONCLUSIONS: For normalization purposes in gene
      profiling studies of bladder cancer the genes SDH and TBP are recommended as
      single reference genes depending on the expression level of the target gene or
      more favorably in combination.

PMID- 16600799
TI  - Polyethylene glycol (molecular weight 400 DA) vehicle improves gene expression of
      adenovirus mediated gene therapy.
AB  - PURPOSE: A significant limitation of adenoviral mediated suicide gene therapy is
      poor gene distribution in vivo. The choice of vehicle has been demonstrated to
      affect the level of adenoviral delivered gene transduction. We examined the
      hypotheses that 1) adenovirus suspended in PEG400 improves gene expression in the
      naive canine prostate model, 2) improved transgene expression with PEG400 results
      in improved tumor control and 3) vehicle affects the initial adenoviral spread
      from a single intratumor injection. MATERIALS AND METHODS: The magnitude and
      volume of gene expression were measured 24 hours following intraprostatic
      injection of adenovirus suspended in PEG400 (12.5% weight per volume) or saline
      as vehicle. Tumor growth delay was measured in mice bearing human tumor
      xenografts following the injection of adenovirus in PEG400 and saline. The
      initial spread of adenovirus was measured by confocal microscopy following a
      single injection of fluorescently labeled adenoviral particles in human tumor
      xenografts using each vehicle. RESULTS: Adenovirus suspended in PEG400 provided
      an average of twice the level of gene expression in the canine prostate and
      significantly better tumor control relative to saline in preclinical tumor models
      (p = 0.046 and 0.036, respectively). The initial spread of adenovirus with PEG400
      was superior to that of adenovirus in saline and the latter was largely limited
      to the needle tract. CONCLUSIONS: Adenoviral gene therapy vectors suspended in
      PEG400 results in improved tumor control because of greater initial adenoviral
      spread, and the increased volume and magnitude of gene expression in vivo.

PMID- 16600800
TI  - Rh2 synergistically enhances paclitaxel or mitoxantrone in prostate cancer
      models.
AB  - PURPOSE: We explored the efficacy of the ginsenoside Rh2 and examined its impact
      on the effective dose of paclitaxel and mitoxantrone in the LNCaP prostate tumor
      model. MATERIALS AND METHODS: Cultured LNCaP cell viability was assessed
      following treatment (48 hours) with Rh2 (0 to 40 microM) alone or in combination
      with paclitaxel and mitoxantrone. Synergism or antagonism observed when combining
      treatment was calculated using CalcuSyn software (Biosoft). In addition, the
      inhibition of LNCaP human xenograft tumor growth was examined in vivo when Rh2
      treatment was combined with chemotherapy. Harvested tumors were
      immunohistochemical stained with p27kip and Ki67. RESULTS: Rh2 and paclitaxel act
      synergistically in cultured LNCaP cells to lower ED50 and ED75 values. Rh2 and
      mitoxantrone are also synergistic. However, when combined as ED95, an
      antagonistic effect was observed in this cell line. Treatment of LNCaP tumors by
      Rh2 plus paclitaxel produced a significant decrease in tumor growth and serum
      prostate specific antigen. Immunohistochemical analysis revealed an apparent but
      nonsignificant effect on proliferation markers in LNCaP tumors. When Rh2 and
      mitoxantrone were combined in vivo, there was no significant benefit observed.
      CONCLUSIONS: These results indicate that the combination of Rh2 and paclitaxel
      has an effect on growth inhibition that is greater and synergistic, as
      demonstrated in a cultured LNCaP cell line. Conversely combining Rh2 with
      mitoxantrone appears to elicit no benefit. Therefore, combination therapy using
      chemotherapy and Rh2 requires further investigation.

PMID- 16600801
TI  - Efficacy of high dose per fraction radiation for implanted human prostate cancer
      in a nude mouse model.
AB  - PURPOSE: SBRT is a new therapeutic paradigm using large dose per fraction
      treatments (aggressive hypofractionation). While SBRT has shown efficacy for
      treating patients with lung, liver and spine tumors, to our knowledge there have
      been no preclinical studies evaluating the efficacy of this treatment for
      prostate cancer. We investigated the dose-response characteristics of SBRT for
      treating human prostate cancer in a nude mouse model. MATERIALS AND METHODS: Nude
      mice were injected subcutaneously into the right flank with C4-2 prostate cancer
      cells grown in culture. A dose escalation trial was performed to assess toxicity
      and response. Tumor bearing animals were radiated with 3 fractions (1 per week)
      for a total dose of 15 Gy in 11, 22.5 Gy in 9 and 45 Gy in 10, while 8 untreated
      animals served as controls. The mice were weighed, and tumor volume and PSA
      measurements were performed at baseline and weekly until 4 weeks after treatment.
      RESULTS: There was no treatment related toxicity. There was a significant
      difference in the tumor response to higher radiation doses. In the 15 and 22.5 Gy
      groups mean tumor volume decreased to 58% and 90% of the original volume,
      respectively, but the rats experienced progressive tumor regrowth within 1 week
      after the completion of therapy. The 45 Gy group had a mean tumor volume and PSA
      decrease of greater than 90%, which was sustained 1 month after treatment in all
      except 2 mice. CONCLUSIONS: SBRT dose level treatments were able to significantly
      decrease tumor volume and PSA. However, using 15 and 22.5 Gy durable responses
      were not achieved except in a few mice. The 45 Gy group demonstrated sustained
      PSA and tumor volume decreases in most mice. These results clearly show an
      increasing dose-response relationship for a range of hypofractionated dose
      levels, as used in SBRT.

PMID- 16600802
TI  - Sexually transmitted infections and prostatic inflammation/cell damage as
      measured by serum prostate specific antigen concentration.
AB  - PURPOSE: Although inflammation and cell damage due to STIs are hypothesized to
      contribute to the later development of prostate disease, few clinical studies
      have been done to investigate the extent to which sexually transmitted agents
      infect and induce an inflammatory immune response in the prostate. We indirectly
      investigated this question by measuring serum PSA, a possible marker of prostatic
      inflammation and cell damage, in men with documented STIs. MATERIALS AND METHODS:
      Archived serum specimens from young men with laboratory confirmed exudative STIs,
      including gonorrhea, chlamydia and trichomonosis, and young men with no STI
      diagnoses were identified in 2 prospective studies of patients at Baltimore City
      STI clinics, that is 84 in the STI Transmission and Acquisition Study, and 61 in
      the Mucosal Immunity Study. Serum specimens from visits before, during and after
      STI diagnoses in men with at least 1 exudative STI diagnosis and from all visits
      in men with no STI diagnoses were tested for total PSA concentration. RESULTS:
      After combining the studies patients with STIs were more likely to have a 40% or
      greater increase in PSA than patients with no STI diagnoses (32% vs 2%, p <0.01).
      CONCLUSIONS: These findings suggest that STIs may contribute to prostatic
      inflammation and cell damage in a subset of infected men. Further studies are
      warranted to replicate study findings and determine host and infection
      characteristics associated with large PSA increases.

PMID- 16600803
TI  - The effect of cyanoacrylic glue on rat testis, urethra and spongiosal tissue: an
      experimental study.
AB  - PURPOSE: We examined the effect of Glubran2 on the rat urethra and spongiosal
      tissue as well as the histopathological effect. We also investigated its clinical
      use. MATERIALS AND METHODS: Eight control and 12 study group male Wistar rats
      were used in our study. The corpus spongiosum tissues, including the urethra and
      the tunica albuginea of the testis, were cut 0.5 and 0.2 cm long, respectively.
      Incision areas in the control group were sutured. In the study group Glubran2 was
      dripped on the area. Three weeks later all rats were sacrificed. The penile and
      testicular tissues were histopathologically investigated. One-way ANOVA and the t
      test were applied for statistical analysis. RESULTS: When the study group was
      compared with the control group, the difference in urethral healing (p = 0.001),
      urethral lumen irregularity (p = 0.036), spongiosal tissue healing (p = 0.001),
      inflammation (p = 0.000), hyperemia-bleeding (p = 0.036) and total healing (p =
      0.001) were statistically significant. When the study and control groups were
      compared, the difference in inflammation (p = 0.000), necrotic areas (p = 0.002),
      tunica albuginea irregularity (p = 0.005), Sertoli's and Leydig cell destruction
      (p = 0.005), and testicular spermatogenesis (p = 0.005) were statistically
      significant. CONCLUSIONS: While perfect healing in the urethral and spongiosal
      tissues supports the clinical application, damage to the seminiferous tubules,
      decreased spermatogenesis at the operated site, tunica albuginea irregularity in
      a fourth of the testes and calcification in 1 testis were observed.

PMID- 16600804
TI  - Effect of estrogen on urethral function and nerve regeneration following pudendal
      nerve crush in the female rat.
AB  - PURPOSE: We tested the hypothesis that estrogen promotes improvement in urethral
      function and nerve regeneration following bilateral pudendal nerve crush in
      ovariectomized female rats. MATERIALS AND METHODS: A total of 52 female rats
      underwent ovariectomy 6 days before bilateral pudendal nerve crush. Estrogen and
      sham capsules were subcutaneously implanted at the time of nerve crush in 16 and
      14 of these rats, respectively, while 22 served as unoperated controls. Seven
      days following nerve crush urethral LPP testing was performed using urethane
      anesthesia. Spinal cord sections containing motoneurons of Onufrowicz's nucleus
      were subjected to in situ hybridization to detect the expression of beta(II)
      tubulin mRNA, a marker of the neuroregenerative response. RESULTS: Mean LPP +/-
      SEM was significantly decreased after pudendal nerve crush in sham treated
      animals compared to unoperated controls (32.1 +/- 6.8 vs 54.4 +/- 11.6 cm H2O).
      Rats with an estrogen implant had an LPP of 42.5 +/- 16.8 cm H2O, which was
      significantly greater than rats given sham implants and significantly less than
      unoperated controls. Rats that received an estrogen implant had increased
      beta(II) tubulin mRNA expression compared to those that received a sham implant.
      CONCLUSIONS: The results of this research suggest that estrogen given at the time
      of pudendal nerve crush promotes and facilitates the recovery of urethral
      function and an increase in the nerve regenerative response. Future studies will
      include the investigation of molecular pathways activated by estrogen in response
      to peripheral nerve injury.

PMID- 16600805
TI  - Characterization of intracavernous pressure increase induced by Ym348, a novel 5
      HT2C receptor agonist, in anesthetized rats.
AB  - PURPOSE: We investigated the effects of the novel 5-HT2C receptor agonist YM348
      [(S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine] on ICP in
      anesthetized rats and clarified whether behavioral changes such as hypolocomotion
      induced at a high dose are a cause of the inverted U-shaped PE dose-response
      curves in conscious rats. MATERIALS AND METHODS: Male Wistar rats (Japan SLC,
      Shizuoka, Japan) weighing 250 to 315 gm were used. The pro-erectile effect of
      YM348 (2.03 to 67.7 microg/kg subcutaneously) was examined in conscious rats. ICP
      was also monitored after YM348 treatment (0.677 to 67.7 mug/kg subcutaneously) in
      anesthetized rats. Response number, latency, duration, peak pressure and area
      under the curve were measured. The selective 5-HT2C receptor antagonist SB242084
      [(6-chloro-5-methyl-1-[6-(2-methylpyridin-3-yloxy) pyridin-3-yl carbamoyl]
      indoline)] (0.03 to 1 mg/kg intraperitoneally) was administered 30 minutes before
      YM348 treatment. RESULTS: YM348 induced PE and ICP increases, and was
      significantly inhibited by SB242084. Dose-response curves for the number of PEs
      and ICP increases were an inverted U shape. YM348 decreased the latency of but
      did not affect the quality of ICP (duration, peak pressure and area under the
      curve) even at the highest dose. CONCLUSIONS: Activation of 5-HT2C receptor
      increased ICP and, as a result, induced PE. Since the dose-response curve for the
      number of ICP increases under anesthetized, behavior independent conditions still
      showed an inverted U shape, behavioral changes were not likely to have
      contributed to the inverted U-shaped dose-response curves for the number of PEs
      in conscious rats. Furthermore, the certain magnitude of ICP increases was likely
      to have occurred despite the stimulus intensity after the level of 5-HT2C
      receptor activation crossed the threshold.

PMID- 16600806
TI  - Re: Has a 3-fold decreased dose of bacillus Calmette-Guerin the same efficacy
      against recurrences and progression of T1G3 and Tis bladder tumors than the
      standard dose? Results of a prospective randomized trial.

PMID- 16600807
TI  - Re: A novel computer based expert decision making model for prostate cancer
      disease management.

PMID- 16600808
TI  - Re: Editorial comment on Laparoscopic radical prostatectomy: is intact organ
      removal attainable? Study of margin status.

PMID- 16600809
TI  - Re: Incidence and management of gynecomastia in men treated for prostate.

PMID- 16600810
TI  - Re: A prospective, randomized, placebo controlled, double-blind study of pelvic
      electromagnetic therapy for the treatment of chronic pelvic pain syndrome with 1
      year of followup.

PMID- 16600811
TI  - Re: A hybrid technique using bipolar energy in transurethral prostate surgery: a
      prospective, randomized comparison.

PMID- 16600812
TI  - Re: Epididymal sparing bilateral simple orchiectomy with epididymoplasty:
      preservation of esthetics and body image.

PMID- 16600813
TI  - Re: Combined buccal mucosa graft and local flap for urethral reconstruction in
      various forms of hypospadias.

PMID- 16600814
TI  - Recent developments in estuarine ecology and management.

PMID- 16600815
TI  - The concept of biotope in marine ecology and coastal management.
AB  - The term "biotope" was introduced by a German scientist, Dahl in 1908 as an
      addition to the concept of "biocenosis" earlier formulated by Mobius (1877).
      Initially it determined the physical-chemical conditions of existence of a
      biocenosis ("the biotope of a biocenosis"). Further, both biotope and biocenosis
      were respectively considered as abiotic and biotic parts of an ecosystem. This
      notion ("ecosystem = biotope + biocenosis") became accepted in German, French,
      Russian and other European "continental" ecological literature. The new
      interpretation of the term ("biotope = habitat + community") appeared in the
      United Kingdom in the early 1990s while classifying "marine habitats" of the
      coastal zone. Since then, this meaning was also used in international European
      environmental documents. This paper examines the evolution of the biotope notion.
      It is concluded that the contemporary concept is robust and may be used not only
      for the classification and mapping but also for functional marine ecology and
      coastal zone management.

PMID- 16600816
TI  - Limited effect of eicosapentaenoic acid on T-lymphocyte and natural killer cell
      numbers and functions in healthy young males.
AB  - OBJECTIVE: Greatly increasing the amount of long-chain omega-3 polyunsaturated
      fatty acids in the diet has been reported in some studies to decrease T
      lymphocyte and natural killer functions. However, dose-response relations have
      not been identified. The objective of this study was to determine the effect of
      supplementing the diet of young male subjects with different amounts of an oil
      rich in eicosapentaenoic acid (EPA) on T-lymphocyte proliferation, cytokine
      production by T lymphocytes, and natural killer cell activity. METHODS: In a
      placebo-controlled, double-blind, parallel study, healthy young (18 to 42 y)
      males were randomized to one of four supplements. These were placebo (no
      additional omega-3 polyunsaturated fatty acids) or different amounts of an EPA
      rich oil that provided 1.35, 2.7, or 4.05 g/d of EPA for 12 wk. Blood samples
      were taken at baseline and after 12 wk. RESULTS: Eicosapentaenoic acid was
      incorporated in a linear dose-response fashion into mononuclear cell
      phospholipids. EPA did not alter the proportions of T lymphocytes, helper T
      lymphocytes, cytotoxic T lymphocytes, B lymphocytes, or natural killer cells in
      the bloodstream. T-lymphocyte proliferation in response to concanavalin A and the
      production of the cytokines interleukin-2, interferon-gamma, and interleukin-10
      were not affected by the different treatments. However, interleukin-4 production
      was increased with increasing intake of EPA. Natural killer cell activity was
      little affected by the treatments, although there was a trend for EPA to increase
      activity at a low effector-to-target cell ratio. CONCLUSION: T-lymphocyte and
      natural killer cell numbers and function in healthy young males are little
      affected by supplemental EPA intakes up to 4 g/d.

PMID- 16600817
TI  - Effects of leucine supplementation on the body composition and protein status of
      rats submitted to food restriction.
AB  - OBJECTIVE: Acute administration of leucine has been shown to stimulate certain
      protein synthesis related anabolic processes. However, the effect of chronic
      leucine administration in a catabolic situation caused by food restriction (FR)
      has not been established. We therefore evaluated the effect of chronic leucine
      supplementation on the body composition and some indicators of protein
      nutritional status of rats submitted to FR. METHODS: Adult male Wistar rats were
      submitted to 50% FR for 6 weeks. The control group received the AIN-93M diet and
      the leucine group received the same diet supplemented with 5.91 g L-leucine/kg
      ration. We then determined carcass chemical composition, serum leptin, albumin
      and total protein concentrations, and protein, DNA and RNA concentrations in
      gastrocnemius muscle and liver. RESULTS: No difference in final body weight was
      observed between groups. However, the leucine group presented a lower amount of
      body fat (P < 0.05). Leptin concentration showed a directly proportional
      correlation with the amount of body fat (r = 0.88, P < 0.05), but no significant
      difference in serum leptin concentration was observed between groups (P = 0.08).
      Regarding protein nutritional status, liver protein concentration was higher in
      the leucine group (P < 0.05). In the gastrocnemius muscle, a higher RNA
      concentration (P < 0.05) and a tendency towards higher DNA concentration (P =
      0.06) were observed in the leucine group. CONCLUSION: The results indicate that
      low-dose leucine supplementation increases body fat loss and improves liver
      protein status and the capacity of muscle protein synthesis in rats submitted to
      FR.

PMID- 16600818
TI  - Effects of Japanese torreya (Torreya nucifera) seed oil on lipid metabolism in
      rats.
AB  - OBJECTIVE: We investigated effects of Japanese torreya (Torreya nucifera) seed
      oil containing non-methylene-interrupted polyunsaturated fatty acid of all-cis
      5,11,14-eicosatrienoic acid (sciadonic acid) on rat lipid metabolism. METHODS:
      Male Sprague-Dawley rats were fed the experimental diets based on AIN-93
      containing 10% corn, soybean, or torreya oil for 4 wk. Blood and tissues were
      recovered from each rat, and concentrations of triacylglycerol, cholesterol, and
      phospholipid in plasma and liver were determined by enzymatic assays. Moreover,
      fatty acid composition was analyzed for triacylglycerol, cholesterol ester, and
      phospholipid isolated from plasma and liver lipids by gas liquid chromatography.
      RESULTS: Plasma triacylglycerol level in rats fed torreya oil was lower than that
      in rats fed corn or soybean oil, although there were no significant differences
      in plasma cholesterol and phospholipid levels in all rats. Liver triacylglycerol
      level was also lower in rats fed torreya oil, whereas liver cholesterol and
      phospholipid levers were same for all rats. omega-3 Polyunsaturated fatty acids
      such as 22:6 (omega-3) were lower in plasma and liver lipids of torreya and corn
      oil groups, whereas omega-6 polyunsaturated fatty acids such as 22:4 (omega-6)
      and 22:5 (omega-6) were higher. Considerable amounts of sciadonic acid were
      detected in cholesterol ester, triacylglycerol, and phospholipid in plasma and
      liver of rats fed torreya oil. CONCLUSION: These observations suggest that
      torreya seed oil can modify lipid metabolism, resulting in lower triacylglycerol
      levels in plasma and liver of rats.

PMID- 16600819
TI  - Severe acute liver damage in anorexia nervosa: two case reports.
AB  - OBJECTIVE: Two female patients (18 and 30 y old, body mass indexes 14.1 and 13.2
      kg/m2) with severe, restrictive anorexia nervosa developed sudden severe liver
      damage. In addition to overt protein-energy malnutrition, they showed marked
      hypotension, bradycardia, dry skin, acrocyanosis, and hypothermia. Most common
      causes of liver failure, such as hepatotropic viruses, hepatotoxic drugs,
      alcohol, cannabis, and cocaine abuse, were excluded. METHODS: Therapeutic
      intervention consisted of immediate plasma volume support, progressive parenteral
      or oral nutritional rehabilitation, and parenteral potassium and phosphorus
      supplements to avoid the refeeding syndrome. RESULTS AND CONCLUSION: Improvement
      of initial clinical symptoms and rapid recovery of liver enzymes after this type
      of treatment suggest that severe liver damage in anorexia nervosa may be
      secondary to acute hypoperfusion.

PMID- 16600820
TI  - Nutrition and health economics.

PMID- 16600821
TI  - Confounding: regression adjustment.

PMID- 16600822
TI  - Quality of life and dietary intake in elderly patients with dysphagia.

PMID- 16600824
TI  - The propofol debate continues.

PMID- 16600826
TI  - Re: the history of ASPAN standards.

PMID- 16600828
TI  - Droperidol's effect on QT interval.
AB  - The Food and Drug Administration (FDA) issued a letter to health care providers
      on December 4, 2001, concerning the medication, droperidol. The purpose of the
      warning was to alert health care providers to the possible role of droperidol in
      the development of torsades de pointes (TdP) in susceptible patients. The purpose
      of this article is to explore the role of droperidol in the development of TdP in
      susceptible patients and current recommendations for the use of droperidol as an
      antiemetic.

PMID- 16600829
TI  - A description of intraoperative and postanesthesia complication rates.
AB  - This article reviews the current rate of intraoperative and postanesthesia
      complications in an acute care hospital and Level II Trauma center. One thousand
      patients were assessed for intraoperative and postoperative complications and
      compared with a previous study from 1991 in a different institution. The overall
      rate of complications in this current study indicated an overall complication
      rate (combined intraoperative and PACU) of 26% with an intraoperative rate of
      3.8% and a PACU rate of 23.4%. Although a slight improvement from a study in
      1991, there continue to be many similarities.

PMID- 16600830
TI  - Applying cultural competence to perianesthesia nursing.
AB  - The paper stresses the importance of cultural competence in perianesthesia
      nursing, both in terms of caring for the patient and in dealing with the
      patient's family. Cultural variations in gender, decision-making, family,
      communication, and time orientation are presented. A distinction is made between
      generalizations (potentially useful) and stereotypes (potentially harmful).
      Several suggestions for specific ways to provide more culturally appropriate care
      are presented, and resources for further study are provided.

PMID- 16600831
TI  - Implications of obstructive sleep apnea syndrome for the perianesthesia nurse.
AB  - Perianesthesia nurses care for patients who receive anesthesia, sedation, and
      analgesia. Anesthesia, sedation, and analgesia can adversely affect the patient
      with obstructive sleep apnea syndrome (OSAS). Increased patient morbidity and
      mortality have been associated with the perianesthesia management of the patient
      with OSAS and can potentially impact every phase of the perianesthesia
      experience. Negative outcomes have been associated with respiratory arrest after
      the administration of opioid or sedative medications, difficult intubation or
      failure to intubate, and respiratory obstruction after extubation. It is
      important for the perianesthesia nurse to identify the implications of OSAS and
      respond with appropriate patient management strategies. The purpose of this
      article is to identify perianesthesia implications associated with the patient
      with formally diagnosed OSAS, patient characteristics that may imply undiagnosed
      OSAS, and considerations for the management of the patient with OSAS for each
      phase of the perianesthesia experience. The new ASA practice guidelines developed
      to assist the practitioner in the decision-making process for the management of
      this patient population have been incorporated.

PMID- 16600832
TI  - Thyroid storm.

PMID- 16600833
TI  - Reconciliation of medications.

PMID- 16600834
TI  - The propofol controversy.

PMID- 16600835
TI  - Insulin and antidiabetic agents -- the old and the new.

PMID- 16600836
TI  - Anesthesia awareness.

PMID- 16600837
TI  - The culture of nursing.

PMID- 16600838
TI  - Vegetarianism, dietary restraint and feminist identity.
AB  - OBJECTIVE: Research examining the relationship between dietary restraint and
      vegetarianism has yielded inconsistent results due to differing definitions of
      vegetarianism and the possible modifying role of feminist identity. The current
      study sought to further clarify these relationships by examining three levels of
      vegetarianism, motivation for vegetarianism, and feminist identity (using an
      updated measure). METHOD: Participants were 90 female undergraduate students and
      community members (mean age=24.34 years). Dietary restraint was measured using
      the TFEQ; feminism was assessed using the LFAIS. RESULTS: Weight-motivated semi
      vegetarians reported higher levels of dietary restraint than those not motivated
      by weight. This effect did not appear among full-vegetarians. Lowest levels of
      dietary restraint were found among full-vegetarians with no difference between
      non- and semi-vegetarians. Contrary to previous research, feminist identity did
      not moderate the relationship between dietary restraint and vegetarianism.
      DISCUSSION: Limitations resulting from a scale with a narrow definition of
      feminism and the use of multiple sources of recruitment are discussed. Directions
      for future research are highlighted.

PMID- 16600839
TI  - An assessment of obese and non obese girls' metabolic rate during television
      viewing, reading, and resting.
AB  - While childhood obesity has been linked to television (TV) viewing, specific
      mechanisms are not well understood. Obesity related to TV viewing might plausibly
      be related to decreased physical activity, increased food intake, reductions in
      metabolic rate, or combinations of these. The current investigation sought to
      ascertain the metabolic effects of quiet rest, listening to a story, watching a
      passive TV program, and watching an active TV show. Counter-balanced conditions
      were presented to 90 pre-pubertal girls ranging in body mass index from
      underweight to obese. In addition, effects between resting energy expenditure
      (REE) and race, body mass index, skinfold measures, physical activity, pubertal
      stage and average hours spent viewing TV were explored. Results indicated no
      significant differences in metabolic rate between weight groups nor between
      activity conditions (story listening and TV viewing) and rest conditions. A
      significant dose-response relationship was found in which REE decreased as
      average weekly hours of TV viewing increased, after adjusting for body mass index
      and puberty stage. Additionally, later stages of pubertal development compared to
      earlier stages were related to higher levels of REE. Results of this study
      suggest that metabolic rate alone cannot account for the consistently observed
      relationship between television viewing and obesity. Future studies should focus
      on energy intake, physical inactivity, or combinations of these with metabolic
      rate in seeking specific mechanisms responsible for television viewing related to
      obesity.

PMID- 16600840
TI  - Weight change in treatment with olanzapine and a psychoeducational approach.
AB  - This study assesses the efficacy of an educational and dietary approach in
      preventing olanzapine-induced weight gain. Eighteen patients affected by
      schizophrenic disorders were treated with olanzapine and weighed twice-weekly for
      24 weeks. A psychoeducational intervention and referral to a nutritionist was
      introduced from the beginning of olanzapine treatment in 9 patients, and from the
      9th week of therapy in 8 patients. Results showed that after 8 weeks of
      olanzapine treatment, weight gain was contained in the subjects receiving
      intervention unlike patients without preventive intervention (+0.99+/-3.34 kg vs.
      +2.96+/-3.08 kg; p<.03). At the end of the trial these patients partly shed their
      gain (-1.77 kg), presenting a final weight which was not significantly different
      from baseline (+1.19 kg). Subjects receiving the psychoeducational approach from
      the beginning were significantly heavier than at baseline (+3.4 kg). Poor dietary
      compliance correlated significantly with an increase in body weight, while higher
      mean dosages of olanzapine correlated with better weight-gain control.

PMID- 16600841
TI  - The relationship between different levels of cognition and behavioural symptoms
      in the eating disorders.
AB  - BACKGROUND: Both disorder-specific cognitions and unconditional core beliefs have
      been associated with eating-disordered behaviours. This study examines whether
      these beliefs might provide competing or complementary explanations of those
      behaviours. METHOD: The participants were 151 women with eating disorders. Each
      woman completed two self-report measures-the Eating Disorder Examination
      Questionnaire (measuring disorder-specific cognitions and reported behavioural
      frequency) and the Young Schema Questionnaire-Short version (measuring
      unconditional core beliefs). Objective height and weight were measured to give
      body mass index (BMI). Regression analyses were used to compare additive,
      mediator and moderator models of the cognition-behaviour link. RESULTS: BMI and
      reported frequency of vomiting were best explained by models where the impact of
      disorder-specific cognitions was moderated by unhealthy core beliefs, but where
      neither form of belief had an independent effect. In contrast, the frequency of
      reported objective binge-eating was best explained by an additive effect of the
      two forms of cognition. DISCUSSION: The findings indicate that both disorder
      specific cognitions and unconditional core beliefs are necessary to explain the
      development and maintenance of disordered eating behaviours. This conclusion
      suggests that cognitive-behavioural approaches might be more effective if they
      address both levels of cognition. However, prospective research is required to
      confirm the causal hypothesis based on the present cross-sectional data.

PMID- 16600842
TI  - Sociocultural values of appearance and attachment processes: An integrated model
      of eating disorder symptomatology.
AB  - Sociocultural and attachment processes were integrated into a single model
      predicting eating disorder symptomatology to determine their relative influence.
      Using normative, self-report data from 146 female undergraduates, path analyses
      tested the fit of a conceptual model with two hypothesized pathways: (1) higher
      awareness of sociocultural values about appearance would lead to less perceived
      appearance satisfaction which would, in turn, lead to eating disordered behavior,
      and (2) attachment avoidance and anxiety (modeled separately) across mother,
      father, and romantic partner domains would predict psychological correlates of
      eating disorders, thereby increasing risk for disordered behaviors. Although both
      were significant, the sociocultural path was slightly stronger (beta=-.46; path
      from attachment/psychological correlates to behaviors beta=.27). Further,
      attachment avoidance exhibited stronger effects than anxiety (explaining 31% and
      25% of variance in psychological correlates, respectively). Results underscored
      the need to consider multiple factors in eating disorder research and treatment
      programs.

PMID- 16600843
TI  - Differential processing of self-referenced versus other-referenced body
      information among American and Chinese young adults with body image concerns.
AB  - Two experiments assessed the impact of self-referenced and other-referenced
      primes on processing of body-related information in samples of young adults from
      the United States and China. In Experiment 1, 46 American university students (41
      females, 5 males) comprising groups higher and lower in body weight concerns
      engaged in a computer-based experiment wherein subliminal self-relevant (I) and
      other-related (He) primes were followed by positive and negative body words to be
      correctly classified as such. Relative to control group participants, those high
      in weight concerns had slower response latencies when classifying words presented
      with an I prime, especially positive I-primed words, compared to He-primed body
      words. This pattern was not observed for control words. In a second experiment
      comprised of 48 Chinese university students (45 females, 3 males), respondents
      high in weight concerns were again slower responding to I-primed body words
      relative to He-primed body words and control group participants. Consistent with
      cognitive perspectives identifying self-schemata as a central basis for body
      image disturbances, findings indicated both Chinese and American young adults
      with concerns about body weight experience interference in processing body
      information linked to the self.

PMID- 16600844
TI  - Weight concerns, body image, depression and anxiety in Swedish adolescents.
AB  - OBJECTIVES: To assess weight problems and correlates in respect of body image,
      depression, anxiety and demographic background factors. METHOD: 405 Swedish
      adolescents were assessed in respect of Body Mass Index (BMI), biographical data,
      the Body Esteem Scale for Adolescents and Adults (BESAA), the Multidimensional
      Anxiety Scale for Children (MASC) and the Children's Depression Inventory (CDI).
      RESULTS: Boys were in the positive and girls in the negative direction from ideal
      BMI for age and gender. Girls and boys differed in respect of CDI, MASC and of
      BESAA where girls generally were shifted in the "pathological" direction.
      DISCUSSION: The adolescents' own positive attitude to slimness, negative mood
      (girls), and anxiety symptoms that reflect social fears (boys) and physical
      aspects of anxiety (girls and boys) were important correlates of lower BMI than
      ideal. Adolescent cultural norms need to be addressed in preventive work.
      However, in girls' separation anxiety might be a protective factor against
      underweight. In girls, overweight seems to be associated with negative self
      esteem.

PMID- 16600845
TI  - Beliefs about the determinants of body weight predict dieting and exercise
      behavior.
AB  - This study examined the relation between beliefs about the determinants of body
      weight and self-reported weight-control behaviors. Restrained eaters and
      unrestrained eaters indicated their beliefs about amount of food eaten and amount
      of exercise as determinants of body weight. They also reported the extent to
      which they engaged in several dieting behaviors and exercise. For restrained
      eaters (but not for unrestrained eaters), there was a positive correlation
      between beliefs about amount of food eaten as a determinant of body weight and
      self-reported dieting behaviors. For both restrained and unrestrained eaters,
      there was a positive correlation between beliefs about exercise as a determinant
      of body weight and amount of weekly exercise. These results suggest that (a)
      specific beliefs about the determinants of body weight can be useful predictors
      of weight-related behaviors, and (b) restrained eaters are likely to engage in a
      broader range of behaviors aimed at controlling their weight.

PMID- 16600846
TI  - Looking within for vision.
AB  - Channelrhodopsin-2 (ChR2), a directly light-gated cation channel from the green
      alga Chlamydomonas reinhardtii has been shown to be a directly light-switched
      cation-selective ion channel, which employs 11-cis retinal as its chromophore.
      This is the same chromophore as the mammalian photoreceptor's visual pigment
      rhodopsin. Previously, investigators demonstrated that ChR2 can be used to
      optically control neuronal firing by depolarizing the cell. In this issue of
      Neuron, Bi et al. apply viral-mediated gene transfer to deliver ChR2 to retinal
      ganglion cells (RGC) in a rodent model of inherited blindness. In this way, the
      authors have genetically engineered surviving retinal neurons to take on the lost
      photoreceptive function. The conversion of light-insensitive retinal interneurons
      into photosensitive cells introduces an entirely new direction for treatments of
      blinding retinal degeneration.

PMID- 16600847
TI  - Kissing and pinching: synaptotagmin and calcium do more between bilayers.
AB  - Building on recent findings that synaptotagmin (Syt) participates in synaptic
      vesicle endocytosis, Poskanzer et al., in this issue of Neuron, show distinct
      mechanisms by which Syt functions in this process. Most significantly, they show
      (1) that calcium binding to Syt determines the rate but not fidelity of vesicle
      recycling and (2) that mutations in a different Syt domain affect the shape but
      not rate of formation of recycled synaptic vesicles.

PMID- 16600848
TI  - Shining light on spike timing-dependent plasticity.
AB  - Although spike timing-dependent plasticity has been well-characterized in vitro,
      it is less clear to what degree spike timing-dependent plasticity contributes to
      shaping visual system properties in vivo. In this issue of Neuron, two papers by
      Vislay-Meltzer et al. and Mu and Poo provide evidence that STDP contributes to
      the effects of sensory stimuli in refinement of the retinotectal system in
      Xenopus.

PMID- 16600849
TI  - The objects of face perception.
AB  - In a comprehensive series of experiments that combine neural modeling, behavioral
      data, and fMRI, Jiang et al. (this issue of Neuron) advance a general object and
      face classification model, based on a feedforward shape-detector architecture.
      The model accounts for configural face processing as well as for shape-based fMRI
      activation in the fusiform face area (FFA).

PMID- 16600850
TI  - NMDA receptors, glial cells, and clinical medicine.
AB  - Recent reports have overturned a series of dogmas that have been well entrenched
      in the neuroscience literature concerning NMDA-type glutamate receptors (NMDARs).
      The new data show that NMDARs exist on the myelin sheath formed by
      oligodendrocytes, that an uncompetitive NMDAR antagonist has successfully passed
      human clinical trials, and that NMDARs trigger multiple deleterious cascades to
      inflict cellular damage on both neurons and glia during cerebral ischemia
      (stroke). These recent findings bode well for clinical intervention with NMDAR
      antagonists in more neurological disorders than previously thought, including
      multiple sclerosis, cerebral palsy (periventricular leukomalacia), and spinal
      cord injury.

PMID- 16600851
TI  - Synaptic roles of Cdk5: implications in higher cognitive functions and
      neurodegenerative diseases.
AB  - Accumulating evidence indicates that cyclin dependent kinase 5 (Cdk5), through
      phosphorylating a plethora of pre- and postsynaptic proteins, functions as an
      essential modulator of synaptic transmission. Recent advances in the field of
      Cdk5 research have not only consolidated the in vivo importance of Cdk5 in
      neurotransmission but also suggest a pivotal role of Cdk5 in the regulation of
      higher cognitive functions and neurodegenerative diseases. In this review, we
      will discuss the recent findings on the emanating role of Cdk5 as a regulator of
      synaptic functions and plasticity.

PMID- 16600852
TI  - Encoding new episodes and making them stick.
AB  - How do we encode, store, and retrieve new episodic memories, and what are the
      computations performed by the hippocampus during this process? One system that
      has been used to model the brain basis of episodic memory in humans is the study
      of spatial navigation by path integration in rodents. Here I discuss three
      exciting new findings focused on encoding or replay of spatial sequences in the
      rat hippocampus. These findings not only provide important new insight into the
      computations associated with encoding and consolidation of spatial trajectories,
      but may also have implications for understanding key aspects of human episodic
      memory.

PMID- 16600854
TI  - Cooperation between GDNF/Ret and ephrinA/EphA4 signals for motor-axon pathway
      selection in the limb.
AB  - Establishment of limb innervation by motor neurons involves a series of
      hierarchical axon guidance decisions by which motor-neuron subtypes evaluate
      peripheral guidance cues and choose their axonal trajectory. Earlier work
      indicated that the pathway into the dorsal limb by lateral motor column (LMC[l])
      axons requires the EphA4 receptor, which mediates repulsion elicited by ephrinAs
      expressed in ventral limb mesoderm. Here, we implicate glial-cell-line-derived
      neurotrophic factor (GDNF) and its receptor, Ret, in the same guidance decision.
      In Gdnf or Ret mutant mice, LMC(l) axons follow an aberrant ventral trajectory
      away from dorsal territory enriched in GDNF, showing that the GDNF/Ret system
      functions as an instructive guidance signal for motor axons. This phenotype is
      enhanced in mutant mice lacking Ret and EphA4. Thus, Ret and EphA4 signals
      cooperate to enforce the precision of the same binary choice in motor-axon
      guidance.

PMID- 16600853
TI  - Ectopic expression of a microbial-type rhodopsin restores visual responses in
      mice with photoreceptor degeneration.
AB  - The death of photoreceptor cells caused by retinal degenerative diseases often
      results in a complete loss of retinal responses to light. We explore the
      feasibility of converting inner retinal neurons to photosensitive cells as a
      possible strategy for imparting light sensitivity to retinas lacking rods and
      cones. Using delivery by an adeno-associated viral vector, here, we show that
      long-term expression of a microbial-type rhodopsin, channelrhodopsin-2 (ChR2),
      can be achieved in rodent inner retinal neurons in vivo. Furthermore, we
      demonstrate that expression of ChR2 in surviving inner retinal neurons of a mouse
      with photoreceptor degeneration can restore the ability of the retina to encode
      light signals and transmit the light signals to the visual cortex. Thus,
      expression of microbial-type channelrhodopsins, such as ChR2, in surviving inner
      retinal neurons is a potential strategy for the restoration of vision after rod
      and cone degeneration.

PMID- 16600855
TI  - Discrete residues in the c(2)b domain of synaptotagmin I independently specify
      endocytic rate and synaptic vesicle size.
AB  - It has been demonstrated that synapses lacking functional synaptotagmin I (Syt I)
      have a decreased rate of synaptic vesicle endocytosis. Beyond this, the function
      of Syt I during endocytosis remains undefined. Here, we demonstrate that a
      decreased rate of endocytosis in syt(null) mutants correlates with a stimulus
      dependent perturbation of membrane internalization, assayed ultrastructurally. We
      then separate the mechanisms that control endocytic rate and vesicle size by
      mapping these processes to discrete residues in the Syt I C(2)B domain. Mutation
      of a poly-lysine motif alters vesicle size but not endocytic rate, whereas the
      mutation of calcium-coordinating aspartate residues (syt-D3,4N) alters endocytic
      rate but not vesicle size. Finally, slowed endocytic rate in the syt-D3,4N
      animals, but not syt(null) animals, can be rescued by elevating extracellular
      calcium concentration, supporting the conclusion that calcium coordination within
      the C(2)B domain contributes to the control of endocytic rate.

PMID- 16600856
TI  - High-density presynaptic transporters are required for glutamate removal from the
      first visual synapse.
AB  - Reliable synaptic transmission depends not only on the release machinery and the
      postsynaptic response mechanism but also on removal or degradation of transmitter
      from the synaptic cleft. Accumulating evidence indicates that postsynaptic and
      glial excitatory amino acid transporters (EAATs) contribute to glutamate removal.
      However, the role of presynaptic EAATs is unclear. Here, we show in the mouse
      retina that glutamate is removed from the synaptic cleft at the rod to rod
      bipolar cell (RBC) synapse by presynaptic EAATs rather than by postsynaptic or
      glial EAATs. The RBC currents evoked by electrical stimulation of rods decayed
      slowly after pharmacological blockade of EAATs. Recordings of the evoked RBC
      currents from EAAT subtype-deficient mice and the EAAT-coupled anion current
      reveal that functional EAATs are localized to rod terminals. Model simulations
      suggest that rod EAATs are densely packed near the release site and that rods are
      equipped with an almost self-sufficient glutamate recollecting system.

PMID- 16600857
TI  - Synaptic AMPA receptor exchange maintains bidirectional plasticity.
AB  - Activity-dependent synaptic delivery of GluR1-, GluR2L-, and GluR4-containing
      AMPA receptors (-Rs) and removal of GluR2-containing AMPA-Rs mediate synaptic
      potentiation and depression, respectively. The obvious puzzle is how synapses
      maintain the capacity for bidirectional plasticity if different AMPA-Rs are
      utilized for potentiation and depression. Here, we show that synaptic AMPA-R
      exchange is essential for maintaining the capacity for bidirectional plasticity.
      The exchange process consists of activity-independent synaptic removal of GluR1-,
      GluR2L-, or GluR4-containing AMPA-Rs and refilling with GluR2-containing AMPA-Rs
      at hippocampal and cortical synapses in vitro and in intact brains. In GluR1 and
      GluR2 knockout mice, initiation or completion of synaptic AMPA-R exchange is
      compromised, respectively. The complementary AMPA-R removal and refilling events
      in the exchange process ultimately maintain synaptic strength unchanged, but
      their long rate time constants ( approximately 15-18 hr) render transmission
      temporarily depressed in the middle of the exchange. These results suggest that
      the previously hypothesized "slot" proteins, rather than AMPA-Rs, code and
      maintain transmission efficacy at central synapses.

PMID- 16600858
TI  - The kv4.2 potassium channel subunit is required for pain plasticity.
AB  - A-type potassium currents are important determinants of neuronal excitability. In
      spinal cord dorsal horn neurons, A-type currents are modulated by extracellular
      signal-regulated kinases (ERKs), which mediate central sensitization during
      inflammatory pain. Here, we report that Kv4.2 mediates the majority of A-type
      current in dorsal horn neurons and is a critical site for modulation of neuronal
      excitability and nociceptive behaviors. Genetic elimination of Kv4.2 reduces A
      type currents and increases excitability of dorsal horn neurons, resulting in
      enhanced sensitivity to tactile and thermal stimuli. Furthermore, ERK-mediated
      modulation of excitability in dorsal horn neurons and ERK-dependent forms of pain
      hypersensitivity are absent in Kv4.2(-/-) mice compared to wild-type littermates.
      Finally, mutational analysis of Kv4.2 indicates that S616 is the functionally
      relevant ERK phosphorylation site for modulation of Kv4.2-mediated currents in
      neurons. These results show that Kv4.2 is a downstream target of ERK in spinal
      cord and plays a crucial role in pain plasticity.

PMID- 16600859
TI  - Spatiotemporal specificity of neuronal activity directs the modification of
      receptive fields in the developing retinotectal system.
AB  - The precise temporal relation between pre- and postsynaptic activity modulates
      the strength of synaptic connections. Despite its extensive characterization in
      vivo and in vitro, the degree to which spike timing-dependent plasticity can
      shape receptive field properties is unclear. We use in vivo patch-clamp
      recordings of tectal neurons in developing Xenopus tadpoles to control the
      precise timing of action potentials with respect to the arrival of a subset of
      visual inputs evoked by local light stimulation on the retina. The pattern of
      visual inputs onto a tectal neuron was tracked over time by rapid reverse
      correlation mapping of receptive fields. Spike timing-dependent potentiation or
      depression of a subset of synapses reliably shifts the spatial receptive fields
      toward or away from the trained subregion of visual space, respectively. These
      results demonstrate that natural patterns of activity evoked by sensory stimuli
      play an instructive role in the developing nervous system.

PMID- 16600860
TI  - Spike timing-dependent LTP/LTD mediates visual experience-dependent plasticity in
      a developing retinotectal system.
AB  - Sensory experience plays an instructive role in the development of the nervous
      system. Here we showed that visual experience can induce persistent modification
      of developing retinotectal circuits via spike timing-dependent plasticity (STDP).
      Pairing light stimuli with spiking of the tectal cell induced persistent
      enhancement or reduction of light-evoked responses, with a dependence on the
      relative timing between light stimulus and postsynaptic spiking similar to that
      for STDP. Using precisely timed sequential three-bar stimulation to mimic a
      moving bar, we showed that spike timing-dependent LTP/LTD can account for the
      asymmetric modification of the tectal cell receptive field induced by moving bar.
      Furthermore, selective inhibition of signaling mediated by brain-derived
      neurotrophic factor and nitric oxide, which are respectively required for light
      induced LTP and LTD, interfered with moving bar-induced temporally specific
      changes in the tectal cell responses. Together, these findings suggest that STDP
      can mediate sensory experience-dependent circuit refinement in the developing
      nervous system.

PMID- 16600861
TI  - A role in learning for SRF: deletion in the adult forebrain disrupts LTD and the
      formation of an immediate memory of a novel context.
AB  - Whereas significant insight exists as to how LTP-related changes can contribute
      to the formation of long-term memory, little is known about the role of
      hippocampal LTD-like changes in learning and memory storage. We describe a mouse
      lacking the transcription factor SRF in the adult forebrain. This mouse could not
      acquire a hippocampus-based immediate memory for a novel context even across a
      few minute timespan, which led to a profound but selective deficit in explicit
      spatial memory. These animals were also impaired in the induction of LTD,
      including LTD triggered by a cholinergic agonist. Moreover, genes regulating two
      processes essential for LTD-calcium release from intracellular stores and
      phosphatase activation-were abnormally expressed in knockouts. These findings
      suggest that for the hippocampus to form associative spatial memories through LTP
      like processes, it must first undergo learning of the context per se through
      exploration and the learning of familiarity, which requires LTD-like processes.

PMID- 16600862
TI  - Temporal encoding of place sequences by hippocampal cell assemblies.
AB  - Both episodic memory and spatial navigation require temporal encoding of the
      relationships between events or locations. In a linear maze, ordered spatial
      distances between sequential locations were represented by the temporal relations
      of hippocampal place cell pairs within cycles of theta oscillation in a
      compressed manner. Such correlations could arise due to spike "phase precession"
      of independent neurons driven by common theta pacemaker or as a result of
      temporal coordination among specific hippocampal cell assemblies. We found that
      temporal correlation between place cell pairs was stronger than predicted by a
      pacemaker drive of independent neurons, indicating a critical role for synaptic
      interactions and precise timing within and across cell assemblies in place
      sequence representation. CA1 and CA3 ensembles, identifying spatial locations,
      were active preferentially on opposite phases of theta cycles. These observations
      suggest that interleaving CA3 neuronal sequences bind CA1 assemblies representing
      overlapping past, present, and future locations into single episodes.

PMID- 16600863
TI  - Evaluation of a shape-based model of human face discrimination using FMRI and
      behavioral techniques.
AB  - Understanding the neural mechanisms underlying object recognition is one of the
      fundamental challenges of visual neuroscience. While neurophysiology experiments
      have provided evidence for a "simple-to-complex" processing model based on a
      hierarchy of increasingly complex image features, behavioral and fMRI studies of
      face processing have been interpreted as incompatible with this account. We
      present a neurophysiologically plausible, feature-based model that quantitatively
      accounts for face discrimination characteristics, including face inversion and
      "configural" effects. The model predicts that face discrimination is based on a
      sparse representation of units selective for face shapes, without the need to
      postulate additional, "face-specific" mechanisms. We derive and test predictions
      that quantitatively link model FFA face neuron tuning, neural adaptation measured
      in an fMRI rapid adaptation paradigm, and face discrimination performance. The
      experimental data are in excellent agreement with the model prediction that
      discrimination performance should asymptote as faces become dissimilar enough to
      activate different neuronal populations.

PMID- 16600864
TI  - Stabilizers and destabilizers controlling cell cycle oscillators.
AB  - Various destabilizing factors of the ubiquitin system contribute to the synchrony
      and unidirectionality of the cell cycle clock by finely tuning the activity of
      various CDKs. The recent findings of hierarchical and connected waves of cyclin
      stabilizers highlight the complexity of this network.

PMID- 16600865
TI  - Making and breaking nucleic acids: two-Mg2+-ion catalysis and substrate
      specificity.
AB  - DNA and a large proportion of RNA are antiparallel duplexes composed of an
      unvarying phosphosugar backbone surrounding uniformly stacked and highly similar
      base pairs. How do the myriad of enzymes (including ribozymes) that perform
      catalysis on nucleic acids achieve exquisite structure or sequence specificity?
      In all DNA and RNA polymerases and many nucleases and transposases, two Mg2+ ions
      are jointly coordinated by the nucleic acid substrate and catalytic residues of
      the enzyme. Based on the exquisite sensitivity of Mg2+ ions to the ligand
      geometry and electrostatic environment, we propose that two-metal-ion catalysis
      greatly enhances substrate recognition and catalytic specificity.

PMID- 16600866
TI  - Ca2+ regulation in the Na+/Ca2+ exchanger involves two markedly different Ca2+
      sensors.
AB  - The plasma membrane Na+/Ca2+ exchanger (NCX) is almost certainly the major Ca2+
      extrusion mechanism in cardiac myocytes. Binding of Na+ and Ca2+ ions to its
      large cytosolic loop regulates ion transport of the exchanger. We determined the
      solution structures of two Ca2+ binding domains (CBD1 and CBD2) that, together
      with an alpha-catenin-like domain (CLD), form the regulatory exchanger loop. CBD1
      and CBD2 are very similar in the Ca2+ bound state and describe the Calx-beta
      motif. Strikingly, in the absence of Ca2+, the upper half of CBD1 unfolds while
      CBD2 maintains its structural integrity. Together with a 7-fold higher affinity
      for Ca2+, this suggests that CBD1 is the primary Ca2+ sensor. Specific point
      mutations in either domain largely allow the interchange of their functionality
      and uncover the mechanism underlying Ca2+ sensing in NCX.

PMID- 16600867
TI  - Conserved XPB core structure and motifs for DNA unwinding: implications for
      pathway selection of transcription or excision repair.
AB  - The human xeroderma pigmentosum group B (XPB) helicase is essential for
      transcription, nucleotide excision repair, and TFIIH functional assembly. Here,
      we determined crystal structures of an Archaeoglobus fulgidus XPB homolog (AfXPB)
      that characterize two RecA-like XPB helicase domains and discover a DNA damage
      recognition domain (DRD), a unique RED motif, a flexible thumb motif (ThM), and
      implied conformational changes within a conserved functional core. RED motif
      mutations dramatically reduce helicase activity, and the DRD and ThM, which flank
      the RED motif, appear structurally as well as functionally analogous to the MutS
      mismatch recognition and DNA polymerase thumb domains. Substrate specificity is
      altered by DNA damage, such that AfXPB unwinds dsDNA with 3' extensions, but not
      blunt-ended dsDNA, unless it contains a lesion, as shown for CPD or (6-4)
      photoproducts. Together, these results provide an unexpected mechanism of DNA
      unwinding with implications for XPB damage verification in nucleotide excision
      repair.

PMID- 16600868
TI  - Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-Msh6(ATP)
      state capable of hydrolysis-independent movement along DNA.
AB  - The Msh2-Msh6 heterodimer plays a key role in the repair of mispaired bases in
      DNA. Critical to its role in mismatch repair is the ATPase activity that resides
      within each subunit. Here we show that both subunits can simultaneously bind ATP
      and identify the Msh6 subunit as containing the high-affinity ATP binding site
      and Msh2 as containing a high-affinity ADP binding site. Stable binding of ATP to
      Msh6 causes decreased affinity of Msh2 for ADP, and binding to mispaired DNA
      stabilized the binding of ATP to Msh6. Our results support a model in which
      mispair binding encourages a dual-occupancy state with ATP bound to Msh6 and
      Msh2; this state supports hydrolysis-independent sliding along DNA.

PMID- 16600869
TI  - Arginine methylation regulates DNA polymerase beta.
AB  - Alterations in DNA repair lead to genomic instability and higher risk of cancer.
      DNA base excision repair (BER) corrects damaged bases, apurinic sites, and single
      strand DNA breaks. Here, a regulatory mechanism for DNA polymerase beta (Pol
      beta) is described. Pol beta was found to form a complex with the protein
      arginine methyltransferase 6 (PRMT6) and was specifically methylated in vitro and
      in vivo. Methylation of Pol beta by PRMT6 strongly stimulated DNA polymerase
      activity by enhancing DNA binding and processivity, while single nucleotide
      insertion and dRP-lyase activity were not affected. Two residues, R83 and R152,
      were identified in Pol beta as the sites of methylation by PRMT6. Genetic
      complementation of Pol beta knockout cells with R83/152K mutant revealed the
      importance of these residues for the cellular resistance to DNA alkylating agent.
      Based on our findings, we propose that PRMT6 plays a role as a regulator of BER.

PMID- 16600870
TI  - The Rb-related p130 protein controls telomere lengthening through an interaction
      with a Rad50-interacting protein, RINT-1.
AB  - The oncogenic process often leads to a loss of normal telomere length control,
      usually as a result of activation of telomerase. Nevertheless, there are also
      telomerase-independent events that involve a Rad50-dependent recombination
      mechanism to maintain telomere length. Previous work has implicated the Rb family
      of proteins in the control of telomere length, and we now demonstrate that the
      p130 member of the Rb family is critical for telomere length control. p130
      interacts specifically with the RINT-1 protein, previously identified as a Rad50
      interacting protein. We further show that RINT-1 is essential for telomere length
      control. We propose that p130, forming a complex with Rad50 through RINT-1,
      blocks telomerase-independent telomere lengthening in normal cells. Given
      previous work implicating E2F in the control of telomerase gene expression, these
      results thus point to complementary roles for the Rb/E2F pathway in the control
      of telomere length.

PMID- 16600871
TI  - The structure of phage phi29 transcription regulator p4-DNA complex reveals an N
      hook motif for DNA.
AB  - Protein p4 affects the transcriptional switch that divides bacteriophage phi29
      infection in early and late phases. The synthesis of DNA replication proteins and
      p4 takes place in the early phase, while structural, morphogenesis, and lysis
      proteins are synthesized in the late phase. Transcriptional switch by p4 is
      achieved by activating the late promoter A3 and repressing the early promoters
      A2b and A2c. The crystal structure of p4 alone and in complex with a 41 bp DNA,
      including the A3 promoter binding site, helps us to understand how the phage
      cycle is controlled. Protein p4 has a unique alpha/beta fold that includes a DNA
      recognition motif consisting of two N-terminal beta turn substructures, or N
      hooks, located at the tips of an elongated protein homodimer. The two N-hooks
      enter the major groove of the double helix, establishing base-specific contacts.
      A high DNA curvature allows p4 N-hooks to reach two major groove areas three
      helical turns apart, like a bow and its string.

PMID- 16600872
TI  - Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus egg
      extracts.
AB  - Mutations in the Drosophila gene encoding the serine-threonine protein kinase
      Greatwall have previously been shown to disrupt mitotic progression. To
      investigate Greatwall's mitotic function, we examined its behavior in Xenopus egg
      extracts. Greatwall is activated during mitosis by phosphorylation; in vitro
      evidence indicates that maturation promoting factor (MPF) is an upstream kinase.
      Conversely, depletion of Greatwall from mitotic extracts rapidly lowers MPF
      activity due to the accumulation of inhibitory phosphorylations on Cdc2 kinase.
      Greatwall depletion similarly prevents cycling extracts from entering M phase.
      The effects of Greatwall depletion can be rescued by the addition of either wild
      type (wt) Greatwall or a noninhibitable form of Cdc2 kinase. These results
      demonstrate that Greatwall participates in an autoregulatory loop that generates
      and maintains sufficiently high MPF activity levels to support mitosis.

PMID- 16600874
TI  - Unfolding of mRNA secondary structure by the bacterial translation initiation
      complex.
AB  - Translation initiation is a key step for regulating the level of numerous
      proteins within the cell. In bacteria, the 30S initiation complex directly binds
      to the translation initiation region (TIR) of the mRNA. How the ribosomal 30S
      subunit assembles on highly structured TIR is not known. Using fluorescence-based
      experiments, we assayed 12 different mRNAs that form secondary structures with
      various stabilities and contain Shine-Dalgarno (SD) sequences of different
      strengths. A strong correlation was observed between the stability of the mRNA
      structure and the association and dissociation rate constants. Interestingly, in
      the presence of initiation factors and initiator tRNA, the association kinetics
      of structured mRNAs showed two distinct phases. The second phase was found to be
      important for unfolding structured mRNAs to form a stable 30S initiation complex.
      We show that unfolding of structured mRNAs requires a SD sequence, the start
      codon, fMet-tRNA(fMet), and the GTP bound form of initiation factor 2 bound to
      the 30S subunit.

PMID- 16600873
TI  - The conserved transmembrane nucleoporin NDC1 is required for nuclear pore complex
      assembly in vertebrate cells.
AB  - Nuclear pore complexes (NPCs) are large proteinaceous channels embedded in the
      nuclear envelope (NE), through which exchange of molecules between the nucleus
      and cytosol occurs. Biogenesis of NPCs is complex and poorly understood. In
      particular, almost nothing is known about how NPCs are anchored in the NE. Here,
      we characterize vertebrate NDC1--a transmembrane nucleoporin conserved between
      yeast and metazoans. We show by RNA interference (RNAi) and biochemical depletion
      that NDC1 plays an important role in NPC and NE assembly in vivo and in vitro.
      RNAi experiments suggest a functional link between NDC1 and the soluble
      nucleoporins Nup93, Nup53, and Nup205. Importantly, NDC1 interacts with Nup53 in
      vitro. This suggests that NDC1 function involves forming a link between the NE
      membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane.

PMID- 16600875
TI  - Posttranscriptional derepression of GADD45alpha by genotoxic stress.
AB  - The growth arrest- and DNA damage-inducible gene GADD45alpha is potently
      upregulated in response to stress stimuli. Here, two RNA binding proteins, the
      mRNA decay-promoting AUF1 and the translational suppressor TIAR, were found to
      interact specifically with the 3' untranslated region (UTR) of the GADD45alpha
      mRNA in HeLa cells. These associations were prominent in unstimulated cells,
      decreasing dramatically after treatment with the genotoxin methyl
      methanesulfonate (MMS). Analysis of both endogenous and chimeric GADD45alpha mRNA
      revealed that in untreated cells AUF1 strongly reduced GADD45alpha mRNA
      stability, whereas TIAR potently inhibited GADD45alpha translation. After
      genotoxic stress, AUF1 and TIAR dissociated from the GADD45alpha mRNA, thereby
      allowing coordinated elevations in both GADD45alpha mRNA half-life and
      translation rate, respectively. We propose that the posttranscriptional
      derepression of GADD45alpha critically contributes to its potent upregulation
      after DNA damage.

PMID- 16600876
TI  - AGO1 homeostasis entails coexpression of MIR168 and AGO1 and preferential
      stabilization of miR168 by AGO1.
AB  - Arabidopsis ARGONAUTE1 (AGO1) encodes the RNA slicer enzyme of the microRNA
      (miRNA) pathway and is regulated by miR168-programmed, AGO1-catalyzed mRNA
      cleavage. Here, we describe two additional regulatory processes required for AGO1
      homeostasis: transcriptional coregulation of MIR168 and AGO1 genes, and
      posttranscriptional stabilization of miR168 by AGO1. Disrupting any of these
      regulatory processes by using mutations or transgenes disturbs a proper
      functioning of the miRNA pathway. In contrast, minor perturbation leads to fine
      tuned posttranscriptional adjustment of miR168 and AGO1 levels, thereby
      maintaining a proper balance of other miRNAs, which, together with AGO1, control
      the mRNA levels of miRNA targets. We suggest that miR168 stabilization occurs at
      the level of silencing-complex assembly and that modulating the efficiency of
      assembling miRNA-programmed silencing complexes will also be important in other
      contexts.

PMID- 16600877
TI  - Structural basis for the specific recognition of methylated histone H3 lysine 4
      by the WD-40 protein WDR5.
AB  - The WD40 repeat protein WDR5 specifically associates with the K4-methylated
      histone H3 in human cells. To investigate the structural basis for this specific
      recognition, we have determined the structure of WDR5 in complex with a
      dimethylated H3-K4 peptide at 1.9 A resolution. Unlike the chromodomain that
      recognizes the methylated H3-K4 through a hydrophobic cage, the specificity of
      WDR5 for methylated H3-K4 is conferred by the nonconventional hydrogen bonds
      between the two zeta-methyl groups of the dimethylated Lys4 and the carboxylate
      oxygen of Glu322 in WDR5. The three amino acids Ala-Arg-Thr preceding Lys4 form
      most of the specific contacts with WDR5, with Ala1 forming intermolecular
      hydrogen bonds and salt bridges, and the side chain of Arg2 inserting into the
      central channel of WDR5. Both structural and biochemical studies presented here
      suggest another mode of recognition for the methylated histone tail.

PMID- 16600878
TI  - Fossilized soft tissues in a Silurian platyceratid gastropod.
AB  - Gastropod shells are common in the fossil record, but their fossil soft tissues
      are almost unknown, and have not been reported previously from the Palaeozoic.
      Here, we describe a Silurian (approx. 425 Myr) platyceratid gastropod from the
      Herefordshire Lagerstatte that preserves the oldest soft tissues yet reported
      from an undoubted crown-group mollusc. The digestive system is preserved in
      detail, and morphological data on the gonads, digestive gland, pedal muscle,
      radula, mouth and foot are also available. The specimen is preserved three
      dimensionally, and has been reconstructed digitally following serial grinding.
      Platyceratids are often found attached to echinoderms, and have been interpreted
      as either commensal coprophages or kleptoparasites. The new data provide support
      for an attached mode of life, and are suggestive of a coprophagous feeding
      strategy. The affinities of the platyceratids are uncertain; they have been
      compared to both the patellogastropods and the neritopsines. Analysis of the new
      material suggests that a patellogastropod affinity is the more plausible of these
      hypotheses.

PMID- 16600879
TI  - Extreme convergence in the body plans of an early suchian (Archosauria) and
      ornithomimid dinosaurs (Theropoda).
AB  - Living archosaurs comprise birds (dinosaurs) and crocodylians (suchians). The
      morphological diversity of birds and stem group dinosaurs is tremendous and well
      documented. Suchia, the archosaurian group including crocodylians, is generally
      considered more conservative. Here, we report a new Late Triassic suchian
      archosaur with unusual, highly specialized features that are convergent with
      ornithomimid dinosaurs. Several derived features of the skull and postcranial
      skeleton are identical to conditions in ornithomimids. Such cases of extreme
      convergence in multiple regions of the skeleton in two distantly related
      vertebrate taxa are rare. This suggests that these archosaurs show iterative
      patterns of morphological evolution. It also suggests that this group of suchians
      occupied the adaptive zone that was occupied by ornithomimosaurs later in the
      Mesozoic.

PMID- 16600880
TI  - Are subspecies useful in evolutionary and conservation biology?
AB  - The taxonomic rank of subspecies remains highly contentious, largely because
      traditional subspecies boundaries have sometimes been contradicted by molecular
      phylogenetic data. The most complete meta-analysis to date, for instance, found
      that only 3% of traditional avian subspecies represented distinct phylogenetic
      lineages. However, the global generality of this phenomenon remains unclear due
      to this previous study's narrow geographic focus on continental Nearctic and
      Palearctic subspecies. Here, we present a new global analysis of avian subspecies
      and show that 36% of avian subspecies are, in fact, phylogenetically distinct.
      Among biogeographic realms we find significant differences in the proportion of
      subspecies that are phylogenetically distinct, with Nearctic/Palearctic
      subspecies showing significantly reduced levels of differentiation. Additionally,
      there are differences between island and continental subspecies, with continental
      subspecies significantly less likely to be genetically distinct. These results
      indicate that the overall level of congruence between taxonomic subspecies and
      molecular phylogenetic data is greater than previously thought. We suggest that
      the widespread impression that avian subspecies are not real arises from a
      predominance of studies focusing on continental subspecies in North America and
      Eurasia, regions which show unusually low levels of genetic differentiation. The
      broader picture is that avian subspecies often provide an effective short-cut for
      estimating patterns of intraspecific genetic diversity, thereby providing a
      useful tool for the study of evolutionary divergence and conservation.

PMID- 16600881
TI  - Evolution of anti-predator traits in response to a flexible targeting strategy by
      predators.
AB  - Anti-predator benefits increase with vigilance rate and group size in many
      species of animal, while simultaneously resource intake rates usually decrease.
      This implies that there is an optimal group size and vigilance rate that will
      maximize individual fitness. While this basic theory of vigilance has been
      modelled and tested extensively, it has often been assumed that the predator
      represents a 'fixed-risk' such that groups of prey are essentially independent
      entities that exert little or no effect on one another either directly or
      indirectly. We argue that this is an over-simplification, and propose that the
      behaviour of one group of prey will likely affect the fitness of another local
      group of prey if the predator preferentially attacks the most vulnerable group
      rather than attack both with constant rates. Using a numerical simulation model,
      we make the first examination of this game and allow the prey to dynamically
      evolve both optimal group size distributions between two habitats and vigilance
      rates in response to a predator with a preference for whichever group is the more
      vulnerable. We show that the density of prey in the population and the
      sensitivity of a predator to differences in prey vulnerability are likely to
      drive the dynamics of such a game. This novel approach to vigilance theory opens
      the door to several challenging lines of future research, both experimental and
      theoretical.

PMID- 16600882
TI  - The evolution of parasite manipulation of host dispersal.
AB  - We investigate the evolution of manipulation of host dispersal behaviour by
      parasites using spatially explicit individual-based simulations. We find that
      when dispersal is local, parasites always gain from increasing their hosts'
      dispersal rate, although the evolutionary outcome is determined by the costs-to
      benefits ratio. However, when dispersal can be non-local, we show that parasites
      investing in an intermediate dispersal distance of their hosts are favoured even
      when the manipulation is not costly, due to the intrinsic spatial dynamics of the
      host-parasite interaction. Our analysis highlights the crucial importance of
      ecological spatial dynamics in evolutionary processes and reveals the theoretical
      possibility that parasites could manipulate their hosts' dispersal.

PMID- 16600883
TI  - Bumble-bee foragers infected by a gut parasite have an impaired ability to
      utilize floral information.
AB  - Parasitic infection can influence a variety of behavioural mechanisms in animals,
      but little is known about the effects of infection on the cognitive processes
      underlying ecologically relevant behaviours. Here, we examined whether parasitic
      infection alters cognitive aspects of foraging in a social insect, the bumble-bee
      (Bombus impatiens). In controlled experiments, we assessed the ability of
      foraging bees to discriminate rewarding from non-rewarding flowers on the basis
      of colour and odour. We found that natural and experimental infection by a
      protozoan parasite (Crithidia bombi, which lives exclusively within the gut
      tract), impaired the ability of foragers to learn the colour of rewarding
      flowers. Parasitic infection can thus disrupt central nervous system pathways
      that mediate cognitive processes in bumble-bees and as a consequence, can reduce
      their ability to monitor floral resources and make economic foraging decisions.
      It is postulated that this infection-induced change to cognitive function in
      bumble-bees is the result of communication between immune and nervous systems.
      Parasitized animals, including invertebrates, can therefore show subtle
      behavioural changes that are nonetheless ecologically significant and reflect
      complex mechanisms.

PMID- 16600884
TI  - Symbiont modifies host life-history traits that affect gene flow.
AB  - The evolution of herbivore-host plant specialization requires low levels of gene
      flow between populations on alternate plant species. Accordingly, selection for
      host plant specialization is most effective when genotypes have minimal exposure
      to, and few mating opportunities with individuals from, alternate habitats.
      Maternally transmitted bacterial symbionts are common in insect herbivores and
      can influence host fecundity under a variety of conditions. Symbiont-mediated
      effects on host life-history strategies, however, are largely unknown. Here, we
      show that the facultative bacterial symbiont Candidatus Regiella insecticola
      strikingly alters both dispersal and mating in the pea aphid, Acyrthosiphon
      pisum. Pea aphids containing Regiella produced only half the number of winged
      offspring in response to crowding and, for two out of three aphid lineages,
      altered the timing of sexual reproduction in response to conditions mimicking
      seasonal changes, than did aphids lacking Regiella. These symbiont-associated
      changes in dispersal and mating are likely to have played a key role in the
      initiation of genetic differentiation and in the evolution of pea aphid-host
      plant specialization. As symbionts are widespread in insects, symbiont-induced
      life history changes may have promoted specialization, and potentially
      speciation, in many organisms.

PMID- 16600885
TI  - Ecological and genetic impact of Atlantic cod larval drift in the Skagerrak.
AB  - We evaluate the hypothesis that Atlantic cod larvae are passively transported by
      sea currents from off-shore spawning areas to settle in coastal waters, a
      hypothesis which has recently gained support from genetic analysis of cod in the
      North Sea-Skagerrak area. Such larval transport has been suggested to be an
      important mechanism behind the commonly observed low spatial genetic
      differentiation in many marine organisms. Here, we apply an ARMAX(2,2) model for
      juvenile abundance and use long-term monitoring data from the Skagerrak coast,
      constituting 54 continuous annual series from 1945 to 1997. Analysing the model,
      we find that the product of the size of the North Sea breeding stock and the
      strength of the net inflow of North Sea waters had a significant, positive effect
      on the abundance of coastal juvenile cod. The peak effect occurs during the month
      of March, just after spawning, when eggs and larvae remain pelagic and sensitive
      to currents. In contrast, we find no evidence of any direct effect of the North
      Sea spawning stock alone. Our analyses indicate that 15-20,000 0-group larvae
      from the North Sea reach each fjord per year, on average. This corresponds to
      about 1-10% of the total 0-group population in each fjord on average. These
      findings clearly demonstrate a direct link between larval drift and gene flow in
      the marine environment.

PMID- 16600886
TI  - Experimental evidence that corticosterone affects offspring sex ratios in quail.
AB  - Recent studies have shown that some species of birds have a remarkable degree of
      control over the sex ratio of offspring they produce. However, the mechanism by
      which they achieve this feat is unknown. Hormones circulating in the breeding
      female are particularly sensitive to environmental perturbations, and so could
      provide a mechanism for her to bias the sex ratio of her offspring in favour of
      the sex that would derive greatest benefit from the prevailing environmental
      conditions. Here, we present details of an experiment in which we manipulated
      levels of testosterone, 17beta-oestradiol and corticosterone in breeding female
      Japanese quail (Coturnix coturnix japonica) using Silastic implants and looked
      for effects on the sex ratio of offspring produced. Offspring sex ratio in this
      species was significantly correlated with faecal concentrations of the principal
      avian stress hormone, corticosterone, and artificially elevated levels of
      corticosterone resulted in significantly female-biased sex ratios at laying.
      Varying testosterone and 17beta-oestradiol had no effect on sex ratio alone, and
      faecal levels of these hormones did not vary in response to corticosterone. Our
      results suggest that corticosterone may be part of the sex-biasing process in
      birds.

PMID- 16600887
TI  - Small body size in an insect shifts development, prior to adult eclosion, towards
      early reproduction.
AB  - Life-history theory has suggested that individual body size can strongly affect
      the allocation of resources to reproduction and away from other traits such as
      survival. In many insects, adults eclose with a proportion of their potential
      lifetime egg production that is already mature (the ovigeny index). We establish
      for the solitary parasitoid wasp Aphaereta genevensis that the ovigeny index
      decreases with adult body size, despite both initial egg load and potential
      lifetime fecundity increasing with body size. This outcome is predicted by
      adaptive models and is the first unequivocal intraspecific demonstration.
      Evidence suggests that a high ovigeny index carries a cost of reduced longevity
      in insects. Our results therefore contribute to the emerging evidence that small
      body size can favour a developmental shift in juveniles that favours early
      reproduction, but which has adverse late-life consequences. These findings are
      likely to have important implications for developmental biologists and population
      biologists.

PMID- 16600888
TI  - Female freshwater crayfish adjust egg and clutch size in relation to multiple
      male traits.
AB  - Females may invest more in reproduction if they acquire mates of high phenotypic
      quality, because offspring sired by preferred partners may be fitter than
      offspring sired by non-preferred ones. In this study, we tested the differential
      maternal allocation hypothesis in the freshwater crayfish, Austropotamobius
      italicus, by means of a pairing experiment aimed at evaluating the effects of
      specific male traits (body size, chelae size and chelae asymmetry) on female
      primary reproductive effort. Our results showed that females laid larger but
      fewer eggs for relatively small-sized, large-clawed males, and smaller but more
      numerous eggs for relatively large-sized, small-clawed males. Chelae asymmetry
      had no effects on female reproductive investment. While the ultimate consequences
      of this pattern of female allocation remain unclear, females were nevertheless
      able to adjust their primary reproductive effort in relation to mate
      characteristics in a species where inter-male competition and sexual coercion may
      mask or obscure their sexual preferences. In addition, our results suggest that
      female allocation may differentially affect male characters, thus promoting a
      trade-off between the expression of different male traits.

PMID- 16600889
TI  - Complex Mhc-based mate choice in a wild passerine.
AB  - The extreme polymorphism of the vertebrate major histocompatibility complex (Mhc)
      is famous for protecting hosts against constantly evolving pathogens. Mate choice
      is often evoked as a means of maintaining Mhc variability through avoidance of
      partners with similar Mhc alleles or preference for heterozygotes. Evidence for
      these two hypotheses mostly comes from studies on humans and laboratory mice.
      Here, we tested these hypotheses in a wild outbred population of house sparrows
      (Passer domesticus). Females were not more or less closely related to the males
      they paired with when considering neutral genetic variation. However, males
      failed to form breeding pairs when they had too few Mhc alleles and when they
      were too dissimilar from females at Mhc loci (i.e. had no common alleles).
      Furthermore, pairs did not form at random as Mhc diversity positively correlated
      in mating pairs. These results suggest that mate choice evolves in response to
      (i) benefits in terms of parasite resistance acquired from allelic diversity, and
      (ii) costs associated with the disruption of co-adapted genes.

PMID- 16600890
TI  - Out of Gondwanaland; the evolutionary history of cooperative breeding and social
      behaviour among crows, magpies, jays and allies.
AB  - Cooperative breeding is comparatively rare among birds in the mainly temperate
      and boreal Northern Hemisphere. Here we test if the distribution of breeding
      systems reflects a response to latitude by means of a phylogenetic analysis using
      correlates with geographical range among the corvids (crows, jays, magpies and
      allied groups). The corvids trace their ancestry to the predominantly cooperative
      'Corvida' branch of oscine passerines from the Australo-Papuan region on the
      ancient Gondwanaland supercontinent, but we could not confirm the ancestral state
      of the breeding system within the family, while family cohesion may be ancestral.
      Initial diversification among pair-breeding taxa that are basal in the corvid
      phylogeny, represented by genera such as Pyrrhocorax and Dendrocitta, indicates
      that the corvid family in its current form could have evolved from pair-breeding
      ancestors only after they had escaped the Australo-Papuan shield. Within the
      family, cooperative breeding (alloparental care/family cohesion) is strongly
      correlated to latitude and its predominance in species maintaining a southerly
      distribution indicates a secondary evolution of cooperative breeding in the
      lineage leading away from the basal corvids. Multiple transitions show plasticity
      in the breeding system, indicating a response to latitude rather than
      evolutionary inertia. The evolutionary background to the loss of cooperative
      breeding among species with a northerly distribution is complex and differs
      between species, indicating a response to a variety of selection forces. Family
      cohesion where the offspring provide alloparental care is a main route to
      cooperatively breeding groups among corvids. Some corvid species lost only
      alloparental care, while maintaining coherent family groups. Other species lost
      family cohesion and, as a corollary, they also lost the behaviour where retained
      offspring provide alloparental care.

PMID- 16600891
TI  - Design complexity and strength of laterality are correlated in New Caledonian
      crows' pandanus tool manufacture.
AB  - Population-level laterality is generally considered to reflect functional brain
      specialization. Consequently, the strength of population-level laterality in
      manipulatory tasks is predicted to positively correlate with task complexity.
      This relationship has not been investigated in tool manufacture. Here, we report
      the correlation between strength of laterality and design complexity in the
      manufacture of New Caledonian crows' three pandanus tool designs: wide, narrow
      and stepped designs. We documented indirect evidence of over 5,800 tool
      manufactures on 1,232 pandanus trees at 23 sites. We found that the strength of
      laterality in tool manufacture was correlated with design complexity in three
      ways: (i) the strongest effect size among the population-level edge biases for
      each design was for the more complex, stepped design, (ii) the strength of
      laterality at individual sites was on average greater for the stepped design than
      it was for the simpler wide and narrow, non-stepped designs, and (iii) there was
      a positive, but non-significant, trend for a correlation between the strength of
      laterality and the number of steps on a stepped tool. These three aspects
      together indicate that greater design complexity generally elicits stronger
      lateralization of crows' pandanus tool manufacture.

PMID- 16600892
TI  - Evidence for a Mullerian mimetic radiation in Asian pitvipers.
AB  - Mullerian mimicry, in which toxic species gain mutual protection from shared
      warning signals, is poorly understood in vertebrates, reflecting a paucity of
      examples. Indirect evidence for mimicry is found if monophyletic species or
      clades show parallel geographic variation in warning patterns. Here, we evaluate
      a hypothesis of Mullerian mimicry for the pitvipers in Southeast Asia using a
      phylogeny derived from DNA sequences from four combined mitochondrial regions.
      Mantel matrix correlation tests show that conspicuous red colour pattern elements
      are significantly associated with sympatric and parapatric populations in four
      genera. To our knowledge, this represents the first evidence of a Mullerian
      mimetic radiation in vipers. The putative mimetic patterns are rarely found in
      females. This appears paradoxical in light of the Mullerian prediction of
      monomorphism, but may be explained by divergent selection pressures on the sexes,
      which have different behaviours. We suggest that biased predation on active males
      causes selection for protective warning coloration, whereas crypsis is favoured
      in relatively sedentary females.

PMID- 16600893
TI  - How much evolutionary history in a 10 x 10 m plot?
AB  - We use a fully dated phylogenetic tree of the angiosperm families to calculate
      phylogenetic diversity (PD) in four South African vegetation types with distinct
      evolutionary histories. Since the branch length values are in this case
      represented by the ages of plant lineages, PD becomes the cumulative evolutionary
      age (CEA) of assemblages. Unsurprisingly, total CEA increases with family and
      with species diversity and observed values are the same as expected from random
      sampling of family lists. However, when random sampling is done from species
      lists, observed CEAs are generally lower than expected. In vegetation types which
      have undergone recent diversification-grassland, fynbos and Nama-karoo-co
      occurring species are more closely related than expected, but in subtropical
      thicket the observed CEAs are well described by random sampling. The use of CEA
      has great potential for assessing the age of biotic assemblages, particularly as
      the dating of genus and species-level phylogenies become more accurate.

PMID- 16600894
TI  - Soil moisture mediates association between the winter North Atlantic Oscillation
      and summer growth in the Park Grass Experiment.
AB  - Several aspects of terrestrial ecosystems are known to be associated with the
      North Atlantic Oscillation (NAO) through effects of the NAO on winter climate,
      but recently the winter NAO has also been shown to be correlated with the
      following summer climate, including drought. Since drought is a major factor
      determining grassland primary productivity, the hypothesis was tested that the
      winter NAO is associated with summer herbage growth through soil moisture
      availability, using data from the Park Grass Experiment at Rothamsted, UK between
      1960 and 1999. The herbage growth rate, mean daily rainfall, mean daily potential
      evapotranspiration (PE) and the mean and maximum potential soil moisture deficit
      (PSMD) were calculated between the two annual cuts in early summer and autumn for
      the unlimed, unfertilized plots. Mean and maximum PSMD were more highly
      correlated than rainfall or PE with herbage growth rate. Regression analysis
      showed that the natural logarithm of the herbage growth rate approximately halved
      for a 250 mm increase in maximum PSMD over the range 50-485 mm. The maximum PSMD
      was moderately correlated with the preceding winter NAO, with a positive winter
      NAO index associated with greater maximum PSMD. A positive winter NAO index was
      also associated with low herbage growth rate, accounting for 22% of the
      interannual variation in the growth rate. It was concluded that the association
      between the winter NAO and summer herbage growth rate is mediated by the PSMD in
      summer.

PMID- 16600895
TI  - Automated biometrics-based personal identification of the Hunter-Schreger bands
      of dental enamel.
AB  - The use of automated biometrics-based personal identification systems is a
      ubiquitous procedure in present times. Biometrics has certain limitations, such
      as in cases when bodies are decomposed, burned, or only small fragments of
      calcified tissues remain. Dental enamel is the most mineralized tissue of
      organisms and resists post-mortem degradation. It is characterized by layers of
      prisms of regularly alternating directions, known as Hunter-Schreger bands (HSB).
      In this article, we show that the pattern variation of the HSB, referred here as
      toothprint, can be used as a biometric-based parameter for personal
      identification in automated systems.

PMID- 16600896
TI  - The greater than twofold cost of integration for retroviruses.
AB  - Sexual reproduction, typically conceived of as a puzzling feature of eukaryotes,
      has posed an extraordinary evolutionary challenge in terms of the twofold
      replicative advantage of asexual over sexual organisms. Here we show
      mathematically that a greater than twofold cost is paid by retroviruses such as
      HIV during reverse transcription. For a retrovirus, replication is achieved
      through RNA reverse transcription and the effectively linear growth processes of
      DNA transcription during gene expression. Retroviruses are unique among viruses
      in that they show an alternation of generations between a diploid free living
      phase and a haploid integrated phase. Retroviruses engage in extensive
      recombination during the synthesis of the haploid DNA provirus. Whereas reverse
      transcription generates large amounts of sequence variation, DNA transcription is
      a high-fidelity process. Retroviruses come under strong selection pressures from
      immune systems to generate escape mutants, and reverse transcription into the
      haploid DNA phase serves to generate diversity followed by a phase of
      transcriptional clonal expansion during the restoration of diploidy from a
      stable, long lived, DNA encoded provirus.

PMID- 16600897
TI  - Quantifying lymphocyte kinetics in vivo using carboxyfluorescein diacetate
      succinimidyl ester (CFSE).
AB  - The cytoplasmic dye carboxyfluorescein diacetate succinimidyl ester (CFSE) is
      used to quantify cell kinetics. It is particularly important in studies of
      lymphocyte homeostasis where its labelling of cells irrespective of their stage
      in the cell cycle makes it preferable to deuterated glucose and BrdU, which only
      label dividing cells and thus produce unrepresentative results. In the past,
      experiments have been limited by the need to obtain a clear separation of CFSE
      peaks forcing scientists to adopt a strategy of in vitro labelling of cells
      followed by their injection into the host. Here we develop a framework for
      analysis of in vivo CFSE labelling data. This enables us to estimate the rate of
      proliferation and death of lymphocytes in situ, and thus represents a
      considerable advance over current procedures. We illustrate this approach using
      in vivo CFSE labelling of B lymphocytes in sheep.

PMID- 16600898
TI  - The atomic force microscope as a tool for studying phase separation in lipid
      membranes.
AB  - Atomic force microscopy has developed into a powerful tool in the study of phase
      separation in lipid bilayers. Its ability to image a semi-fluid surface under
      buffer at nanometre lateral resolution and Angstrom resolution vertically allows
      us to distinguish phase separated lipid domains, models of the elusive rafts
      postulated to exist as functional platforms in the cellular membrane, which may
      only rise 0.3 nm above the surrounding membrane. This review charts the history
      of this development, and includes a description of sample preparation techniques,
      factors affecting image contrast mechanisms, its use in the investigation of the
      pre-transition ripple phase, and in the localization of cell surface proteins.

PMID- 16600899
TI  - The RNA polymerase III-dependent family of genes in hemiascomycetes: comparative
      RNomics, decoding strategies, transcription and evolutionary implications.
AB  - We present the first comprehensive analysis of RNA polymerase III (Pol III)
      transcribed genes in ten yeast genomes. This set includes all tRNA genes (tDNA)
      and genes coding for SNR6 (U6), SNR52, SCR1 and RPR1 RNA in the nine
      hemiascomycetes Saccharomyces cerevisiae, Saccharomyces castellii, Candida
      glabrata, Kluyveromyces waltii, Kluyveromyces lactis, Eremothecium gossypii,
      Debaryomyces hansenii, Candida albicans, Yarrowia lipolytica and the
      archiascomycete Schizosaccharomyces pombe. We systematically analysed sequence
      specificities of tRNA genes, polymorphism, variability of introns, gene
      redundancy and gene clustering. Analysis of decoding strategies showed that
      yeasts close to S.cerevisiae use bacterial decoding rules to read the Leu CUN and
      Arg CGN codons, in contrast to all other known Eukaryotes. In D.hansenii and
      C.albicans, we identified a novel tDNA-Leu (AAG), reading the Leu CUU/CUC/CUA
      codons with an unusual G at position 32. A systematic 'p-distance tree' using the
      60 variable positions of the tRNA molecule revealed that most tDNAs cluster into
      amino acid-specific sub-trees, suggesting that, within hemiascomycetes,
      orthologous tDNAs are more closely related than paralogs. We finally determined
      the bipartite A- and B-box sequences recognized by TFIIIC. These minimal
      sequences are nearly conserved throughout hemiascomycetes and were satisfactorily
      retrieved at appropriate locations in other Pol III genes.

PMID- 16600902
TI  - Could endothelial caveolae be the target of general anaesthetics?

PMID- 16600900
TI  - Identification and characterization of CRT10 as a novel regulator of
      Saccharomyces cerevisiae ribonucleotide reductase genes.
AB  - The CRT10 gene was identified through screening of the Saccharomyces cerevisiae
      deletion library for hydroxyurea (HU) resistance. CRT10 encodes a putative 957
      amino acid, 110 kDa protein with a leucine repeat and a WD40 repeat near the N
      terminus. Deletion of CRT10 resulted in an enhanced resistance to HU reminiscent
      of the inactivation of two other ribonucleotide reductase (Rnr) suppressors, CRT1
      and SML1, which regulate Rnr activity at transcriptional and translational
      levels, respectively. Epistatic analysis indicates that CRT10 belongs to the CRT1
      pathway but not the SML1 pathway. Indeed, deletion of CRT10 enhanced the survival
      of the mec1 null mutant and increased basal level and DNA damage-induced
      expression of RNR2 and RNR3, suggesting that Crt10 regulates RNR genes at the
      transcriptional level. Furthermore, the dun1 mutation is epistatic to crt10 with
      respect to both HU sensitivity and RNR gene expression. Interestingly, the
      expression of CRT10 itself is induced by DNA damaging agents and this induction
      requires DUN1, suggesting that CRT10 plays a role in cellular response to DNA
      damage and replication blocks. The CRT10 function appears to be achieved by
      positive regulation of the CRT1 transcript level, indicating that CRT10 is a
      component of the regulatory circuit.

PMID- 16600901
TI  - Crystal structure of Bacillus subtilis TrmB, the tRNA (m7G46) methyltransferase.
AB  - The structure of Bacillus subtilis TrmB (BsTrmB), the tRNA (m7G46)
      methyltransferase, was determined at a resolution of 2.1 A. This is the first
      structure of a member of the TrmB family to be determined by X-ray
      crystallography. It reveals a unique variant of the Rossmann-fold
      methyltransferase (RFM) structure, with the N-terminal helix folded on the
      opposite site of the catalytic domain. The architecture of the active site and a
      computational docking model of BsTrmB in complex with the methyl group donor S
      adenosyl-L-methionine and the tRNA substrate provide an explanation for results
      from mutagenesis studies of an orthologous enzyme from Escherichia coli (EcTrmB).
      However, unlike EcTrmB, BsTrmB is shown here to be dimeric both in the crystal
      and in solution. The dimer interface has a hydrophobic core and buries a
      potassium ion and five water molecules. The evolutionary analysis of the putative
      interface residues in the TrmB family suggests that homodimerization may be a
      specific feature of TrmBs from Bacilli, which may represent an early stage of
      evolution to an obligatory dimer.

PMID- 16600903
TI  - Standards of care for PONV.

PMID- 16600904
TI  - Stellate ganglion block-therapy for cerebral vascular accidents.

PMID- 16600905
TI  - Pre-emptive analgesia and the paravertebral space -- an ignis fatuus.

PMID- 16600906
TI  - Spontaneous intracranial hypotension: a recent indication for epidural blood
      patch.

PMID- 16600907
TI  - Impossible test or reasonable aim.

PMID- 16600908
TI  - PIAS proteins and transcriptional regulation--more than just SUMO E3 ligases?

PMID- 16600909
TI  - Post-transcriptional small RNA pathways in plants: mechanisms and regulations.
AB  - Small RNAs are riboregulators that have critical roles in most eukaryotes. They
      repress gene expression by acting either on DNA to guide sequence elimination and
      chromatin remodeling, or on RNA to guide cleavage and translation repression.
      This review focuses on the various types of post-transcriptional small RNA
      directed pathways in plants, describing their roles and their regulations.

PMID- 16600910
TI  - PIAS1 confers DNA-binding specificity on the Msx1 homeoprotein.
AB  - The mechanisms by which homeoproteins bind selectively to target genes in vivo
      have long remained unresolved. Here we report that PIAS1 confers DNA-binding
      specificity on the Msx1 homeoprotein by regulating its subnuclear localization
      and proximity to target genes. We demonstrate that the interaction of Msx1 with
      PIAS1, but not its sumoylation, is required for Msx1 to function as an inhibitor
      of myoblast differentiation through repression of myogenic regulatory genes, such
      as MyoD. We find that PIAS1 enables Msx1 to bind selectively to a key regulatory
      element in MyoD, the CER, in myoblast cells and to distinguish the CER from other
      nonregulatory TAAT-containing sequences. We show that PIAS1 is required for the
      appropriate localization and retention of Msx1 at the nuclear periphery in
      myoblast cells. Furthermore, we demonstrate that myogenic regulatory genes that
      are repressed by Msx1, namely MyoD and Myf5, are located at the nuclear periphery
      in myoblast cells. We propose that a key regulatory event for DNA-binding
      specificity by homeoproteins in vivo is their appropriate targeting to subnuclear
      compartments where their target genes are located, which can be achieved by
      cofactors such as PIAS1.

PMID- 16600911
TI  - The novel SAM domain protein Aveugle is required for Raf activation in the
      Drosophila EGF receptor signaling pathway.
AB  - Activation of the Raf kinase by GTP-bound Ras is a poorly understood step in
      receptor tyrosine kinase signaling pathways. One such pathway, the epidermal
      growth factor receptor (EGFR) pathway, is critical for cell differentiation,
      survival, and cell cycle regulation in many systems, including the Drosophila
      eye. We have identified a mutation in a novel gene, aveugle, based on its
      requirement for normal photoreceptor differentiation. The phenotypes of aveugle
      mutant cells in the eye and wing imaginal discs resemble those caused by
      reduction of EGFR pathway function. We show that aveugle is required between ras
      and raf for EGFR signaling in the eye and for mitogen-activated protein kinase
      phosphorylation in cell culture. aveugle encodes a small protein with a sterile
      alpha motif (SAM) domain that can physically interact with the scaffold protein
      connector enhancer of Ksr (Cnk). We propose that Aveugle acts together with Cnk
      to promote Raf activation, perhaps by recruiting an activating kinase.

PMID- 16600912
TI  - A KSR/CNK complex mediated by HYP, a novel SAM domain-containing protein,
      regulates RAS-dependent RAF activation in Drosophila.
AB  - RAF is a critical effector of the small GTPase RAS in normal and malignant cells.
      Despite intense scrutiny, the mechanism regulating RAF activation remains
      partially understood. Here, we show that the scaffold KSR (kinase suppressor of
      RAS), a RAF homolog known to assemble RAF/MEK/ERK complexes, induces RAF
      activation in Drosophila by a mechanism mediated by its kinase-like domain, but
      which is independent of its scaffolding property or putative kinase activity.
      Interestingly, we found that KSR is recruited to RAF prior to signal activation
      by the RAF-binding protein CNK (connector enhancer of KSR) in association with a
      novel SAM (sterile alpha motif) domain-containing protein, named Hyphen (HYP).
      Moreover, our data suggest that the interaction of KSR to CNK/HYP stimulates the
      RAS-dependent RAF-activating property of KSR. Together, these findings identify a
      novel protein complex that controls RAF activation and suggest that KSR does not
      only act as a scaffold for the MAPK (mitogen-activated protein kinase) module,
      but may also function as a RAF activator. By analogy to catalytically impaired,
      but conformationally active B-RAF oncogenic mutants, we discuss the possibility
      that KSR represents a natural allosteric inducer of RAF catalytic function.

PMID- 16600913
TI  - Role of heat-shock factor 2 in cerebral cortex formation and as a regulator of
      p35 expression.
AB  - Heat-shock factors (HSFs) are associated with multiple developmental processes,
      but their mechanisms of action in these processes remain largely enigmatic. Hsf2
      null mice display gametogenesis defects and brain abnormalities characterized by
      enlarged ventricles. Here, we show that Hsf2-/- cerebral cortex displays
      mispositioning of neurons of superficial layers. HSF2 deficiency resulted in a
      reduced number of radial glia fibers, the architectural guides for migrating
      neurons, and of Cajal-Retzius cells, which secrete the positioning signal Reelin.
      Therefore, we focused on the radial migration signaling pathways. The levels of
      Reelin and Dab1 tyrosine phosphorylation were reduced, suggesting that the Reelin
      cascade is affected in Hsf2-/- cortices. The expression of p35, an activator of
      cyclin-dependent kinase 5 (Cdk5), essential for radial migration, was dependent
      on the amount of HSF2 in gain- and loss-of-function systems. p39, another Cdk5
      activator, displayed reduced mRNA levels in Hsf2-/- cortices, which, together
      with the lowered p35 levels, decreased Cdk5 activity. We demonstrate in vivo
      binding of HSF2 to the p35 promoter and thereby identify p35 as the first target
      gene for HSF2 in cortical development. In conclusion, HSF2 affects cellular
      populations that assist in radial migration and directly regulates the expression
      of p35, a crucial actor of radial neuronal migration.

PMID- 16600916
TI  - Tag-team recycling.

PMID- 16600914
TI  - Modulating RssB activity: IraP, a novel regulator of sigma(S) stability in
      Escherichia coli.
AB  - The sigma(S) subunit of Escherichia coli RNA polymerase regulates the expression
      of stationary phase and stress response genes. sigma(S) is highly unstable in
      exponentially growing cells, whereas its stability increases dramatically upon
      starvation or under certain stress conditions. The degradation of sigma(S) is
      controlled by the phosphorylatable adaptor protein RssB and the ClpXP protease.
      RssB specifically directs sigma(S) to ClpXP. An unanswered question is how RssB
      mediated degradation of sigma(S) is blocked by conditions such as glucose or
      phosphate starvation. We report here the identification and characterization of a
      new regulator of sigma(S) stability, IraP (inhibitor of RssB activity during
      phosphate starvation), that stabilizes sigma(S) both in vivo and in vitro.
      Deletion of iraP interferes with sigma(S) stabilization during phosphate
      starvation, but not during carbon starvation, and has a partial effect in
      stationary phase and nitrogen starvation. IraP interferes with RssB-dependent
      degradation of sigma(S) through a direct protein-protein interaction with RssB. A
      point mutant of IraP was isolated and found to be defective both for inhibition
      of sigma(S) degradation and interaction with RssB. Our results reveal a novel
      mechanism of regulation of sigma(S) stability through the regulation of RssB
      activity and identify IraP as a member of a new class of regulators, the anti
      adaptor proteins.

PMID- 16600915
TI  - The transcription factor FLC confers a flowering response to vernalization by
      repressing meristem competence and systemic signaling in Arabidopsis.
AB  - Floral development at the Arabidopsis shoot apical meristem occurs in response to
      environmental cues that are perceived in different tissues. Photoperiod is
      detected in the vascular tissue of the leaf (phloem) and promotes production of a
      systemic signal that induces flowering at the meristem. Vernalization, the
      response to winter temperatures, overcomes a block on photoperiodic floral
      induction. In Arabidopsis, this block is caused by inhibitors of flowering that
      comprise several related MADS-box transcription factors, the most prominent of
      which is FLC. We show that FLC delays flowering by repressing production in the
      leaf of at least two systemic signals, one of which is controlled by the RAF
      kinase inhibitor-like protein FT. Reducing expression of these signals indirectly
      represses expression of genes involved in floral induction at the meristem. In
      addition, FLC expression in the meristem impairs response to the FT signal by
      directly repressing expression of the SOC1 MADS-box transcription factor and
      preventing up-regulation of the bZIP transcription factor FD. Repression of genes
      acting at multiple levels in this hierarchy is required for the extreme delay in
      flowering caused by FLC. An FLC:HA fusion protein binds directly in vivo to the
      promoter regions of FD and SOC1 and to the first intron of FT. Thus vernalization
      relieves transcriptional repression of key regulatory genes in both the leaf and
      meristem, allowing production of systemic signals in the leaves and conferring
      competence on the meristem to respond to these signals.

PMID- 16600917
TI  - Environmental movement.

PMID- 16600918
TI  - SENS and the polarization of aging-related research.
AB  - The second Strategies for Engineered Negligible Senescence conference (SENS II)
      featured some very provocative ideas. The explicit objective of extending human
      life span indefinitely has opened a large rift between the meeting's organizer
      and those who believe he is acting unscientifically, perhaps recklessly. Two SENS
      conference participants present their views on the divisive nature of SENS.

PMID- 16600919
TI  - Aging in check.
AB  - The spindle checkpoint monitors the interaction between spindle microtubules and
      kinetochores to prevent precocious entry into anaphase, delaying this stage of
      mitosis until all condensed chromosomes have been attached to the mitotic spindle
      in a bi-oriented manner (so that the two kinetochores associated with a pair of
      sister chromatids are oriented toward opposite poles of the spindle). In addition
      to conserved Bub and Mad family members, which are known to function in the
      spindle checkpoint pathway in organisms ranging from yeast to mammals, two mRNA
      transport genes, Rae1 and Nup9, are also involved in the spindle checkpoint
      function in mammals. Biochemically, activated spindle checkpoint components have
      been shown to suppress the activity of the anaphase promoting complex/cyclosome.
      It is generally thought that decreased activity of the checkpoint components
      predisposes cells to chromosomal instability, aneuploidy, and malignant
      transformation. Interestingly, a recent study has shed light on a new function of
      the spindle checkpoint components Bub3 and Rae1 in the regulation of aging. Mice
      with haploinsufficiency of Bub3 and Rae1 have a short life span that is
      associated with the early onset of aging-related features. The progeroid
      phenotypes caused by deficiency of Bub3 and Rae1 are tightly linked to precocious
      activation of cellular senescence, but not apoptotic, programs. Therefore,
      premature aging, rather than neoplastic transformation, may be the major
      manifestation of a compromised spindle checkpoint in vivo.

PMID- 16600920
TI  - Vitamin D in congestive heart failure.

PMID- 16600921
TI  - Diet and age-related macular degeneration: expanding our view.

PMID- 16600922
TI  - Cachexia: pathophysiology and clinical relevance.
AB  - Cachexia causes weight loss and increased mortality. It affects more than 5
      million persons in the United States. Other causes of weight loss include
      anorexia, sarcopenia, and dehydration. The pathophysiology of cachexia is
      reviewed in this article. The major cause appears to be cytokine excess. Other
      potential mediators include testosterone and insulin-like growth factor I
      deficiency, excess myostatin, and excess glucocorticoids. Numerous diseases can
      result in cachexia, each by a slightly different mechanism. Both nutritional
      support and orexigenic agents play a role in the management of cachexia.

PMID- 16600923
TI  - Effects of dairy products naturally enriched with cis-9,trans-11 conjugated
      linoleic acid on the blood lipid profile in healthy middle-aged men.
AB  - BACKGROUND: Interest in the development of dairy products naturally enriched in
      conjugated linoleic acid (CLA) exists. However, feeding regimens that enhance the
      CLA content of milk also increase concentrations of trans-18:1 fatty acids. The
      implications for human health are not yet known. OBJECTIVE: This study
      investigated the effects of consuming dairy products naturally enriched in cis
      9,trans-11 CLA (and trans-11 18:1) on the blood lipid profile, the atherogenicity
      of LDL, and markers of inflammation and insulin resistance in healthy middle-aged
      men. DESIGN: Healthy middle-aged men (n = 32) consumed ultra-heat-treated milk,
      butter, and cheese that provided 0.151 g/d (control) or 1.421 g/d (modified) cis
      9,trans-11 CLA for 6 wk. This was followed by a 7-wk washout and a crossover to
      the other treatment. RESULTS: Consumption of dairy products enriched with cis
      9,trans-11 CLA and trans-11 18:1 did not significantly affect body weight,
      inflammatory markers, insulin, glucose, triacylglycerols, or total, LDL, and HDL
      cholesterol but resulted in a small increase in the ratio of LDL to HDL
      cholesterol. The modified dairy products changed LDL fatty acid composition but
      had no significant effect on LDL particle size or the susceptibility of LDL to
      oxidation. Overall, increased consumption of full-fat dairy products and
      naturally derived trans fatty acids did not cause significant changes in
      cardiovascular disease risk variables, as may be expected on the basis of current
      health recommendations. CONCLUSION: Dairy products naturally enriched with cis
      9,trans-11 CLA and trans-11 18:1 do not appear to have a significant effect on
      the blood lipid profile.

PMID- 16600924
TI  - Vitamin D supplementation improves cytokine profiles in patients with congestive
      heart failure: a double-blind, randomized, placebo-controlled trial.
AB  - BACKGROUND: Elevated circulating concentrations of proinflammatory cytokines may
      contribute to the pathogenesis of congestive heart failure (CHF). In vitro
      studies suggest that vitamin D suppresses proinflammatory cytokines and increases
      antiinflammatory cytokines. OBJECTIVE: We evaluated the effect of vitamin D
      supplementation on the survival rate and different biochemical variables in
      patients with CHF. DESIGN: One hundred twenty-three patients randomly received
      either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg
      Ca/d [D(-) group] for 9 mo. Biochemical variables were assessed at baseline and
      after 9 mo. The survival rate was calculated for a follow-up period of 15 mo.
      RESULTS: Ninety-three patients completed the study. Significant treatment effects
      were observed on logarithmic-transformed serum concentrations of 25
      hydroxyvitamin D (P = 0.001), parathyroid hormone (P = 0.007), tumor necrosis
      factor alpha (P = 0.006), and interleukin 10 (P = 0.042). 25-Hydroxyvitamin D
      increased by 26.8 ng/mL in the D(+) group but increased only by 3.6 ng/mL in the
      D(-) group. Compared with baseline, parathyroid hormone was significantly lower
      and the antiinflammatory cytokine interleukin 10 was significantly higher in the
      D(+) group after 9 mo. The proinflammatory cytokine tumor necrosis factor alpha
      increased in the D(-) group but remained constant in the D(+) group. The survival
      rate did not differ significantly between the study groups during the follow-up
      period. CONCLUSIONS: Vitamin D(3) reduces the inflammatory milieu in CHF patients
      and might serve as a new antiinflammatory agent for the future treatment of the
      disease. Our data provide evidence for the involvement of an impaired vitamin D
      parathyroid hormone axis in the progression of CHF.

PMID- 16600925
TI  - Association between dietary fiber and serum C-reactive protein.
AB  - BACKGROUND: High sensitivity C-reactive protein (CRP) is a marker of acute
      inflammation recently recognized as an independent predictor of future
      cardiovascular disease and diabetes. The identification of modifiable factors,
      such as diet, that influence serum CRP concentrations may provide the means for
      reducing the risk of these diseases. Data on longitudinal associations between
      dietary fiber intake and CRP are currently lacking. OBJECTIVE: The purpose of
      this study was to examine longitudinal associations between dietary fiber intake
      and CRP. DESIGN: Data collection took place at baseline and quarterly (every 13
      wk) thereafter for a total of 5 visits, each including measurements of body
      composition, CRP, diet, and physical activity. Relations between serum CRP and
      dietary fiber were assessed by using linear mixed models and logistic regression,
      adjusted for covariates. RESULTS: A total of 524 subjects had multiple
      measurements of CRP and dietary factors. The average total dietary fiber intake
      was 16.11 g/d. Average serum CRP was 1.78 mg/L. We observed an inverse
      association between intake of total dietary fiber (separately for soluble and
      insoluble fiber) and CRP concentrations in both cross-sectional and longitudinal
      analyses. The likelihood of elevated CRP concentrations was 63% lower (OR: 0.37;
      95% CI: 0.16, 0.87) in participants in the highest quartile of total fiber intake
      than in participants in the lowest quartile. CONCLUSIONS: Our results suggest
      that dietary fiber is protective against high CRP, which supports current
      recommendations for a diet high in fiber.

PMID- 16600926
TI  - Association of body mass index measured in childhood, adolescence, and young
      adulthood with risk of ischemic heart disease and stroke: findings from 3
      historical cohort studies.
AB  - BACKGROUND: It is unclear whether early life body mass index (BMI; in kg/m(2)) is
      associated with adult cardiovascular disease. OBJECTIVE: The objective was to
      assess the association of early life BMI with the risk of ischemic heart disease
      (IHD) and stroke. DESIGN: The association between early life BMI and risk of
      adult mortality from IHD and stroke was assessed in 3 historical cohort studies
      in which height and weight had been assessed by using standard procedures.
      Participants were traced and linked to national mortality data. Participants in
      the 3 cohorts were born between 1922 and 1937, 1927 and 1956, and 1928 and 1950
      and were aged 2-15, 9-18, and 16-22 y, respectively, at the time of assessment of
      their height and weight. RESULTS: Participants in all 3 cohorts had mean BMIs
      similar to those reported for contemporary children and young adults, but fewer
      of the cohort participants were overweight or obese. BMI was not associated with
      future risk of IHD or stroke in any cohort. The pooled (all 3 cohorts) adjusted
      hazard ratio per SD of early life BMI was 1.09 (95% CI: 1.01, 1.19) for IHD and
      0.94 (95% CI: 0.82, 1.08) for stroke. The pooled hazard ratio of IHD when
      participants who were overweight or obese for their age were compared with all
      other participants was 1.34 (95% CI: 0.95, 1.91), and no association was found
      between overweight or obesity and stroke risk. The effects of BMI did not vary by
      cohort or by age. CONCLUSION: These results do not provide strong evidence that
      being overweight or obese in childhood is associated with future cardiovascular
      disease risk.

PMID- 16600927
TI  - Responses of inflammatory markers to a low-fat, high-carbohydrate diet: effects
      of energy intake.
AB  - BACKGROUND: Inflammation contributes to atherogenesis. Dietary fats may be
      proinflammatory. OBJECTIVE: The objective was to determine whether energy intake
      modulates the effects of low-fat, high-carbohydrate intakes on inflammatory
      markers. DESIGN: Twenty-two healthy postmenopausal women with a mean (+/-SD) age
      of 61 +/- 11 y, who were not receiving hormone replacement therapy, were fed
      eucaloric diets to reduce their fat intake from 35% to 15% of energy. Next, the
      women consumed a 15%-fat ad libitum diet under free-living conditions. Serum
      highly sensitive C-reactive protein, interleukin 6, HDL serum amyloid A, and
      adiponectin concentrations were measured at the end of the eucaloric and ad
      libitum low-fat, high-carbohydrate intakes. RESULTS: The eucaloric diet decreased
      adiponectin from 16.3 +/- 2.1 to 14.2 +/- 2.0 mg/L (P < 0.05) and increased
      triacylglycerol from 131 +/- 11 to 164 +/- 14 mg/dL (P < 0.01). The ad libitum
      low-fat diet caused 6 kg weight loss and decreased highly sensitive C-reactive
      protein from 4.3 +/- 0.6 to 2.5 +/- 0.5 mg/L (P < 0.01), decreased HDL serum
      amyloid A from 10.3 +/- 1.8 to 5.7 +/- 1.3 mg/L (P < 0.001), increased
      adiponectin from 14.2 +/- 2.0 to 16.3 +/- 1.7 mg/L (P < 0.05), and decreased
      triacylglycerol from 164 +/- 14 to 137 +/- 15 mg/dL (P < 0.05). CONCLUSION:
      During the eucaloric phase, the low-fat, high-carbohydrate diet exerted
      unfavorable effects on the inflammatory markers. In contrast, the ad libitum low
      fat, high-carbohydrate intake caused weight loss and affected inflammatory
      markers favorably. Thus, the energy content of a low-fat, high-carbohydrate diet
      determines changes in inflammatory markers.

PMID- 16600928
TI  - Partial substitution of carbohydrate intake with protein intake from lean red
      meat lowers blood pressure in hypertensive persons.
AB  - BACKGROUND: Compared with carbohydrate intake, dietary intake of plant protein
      can lower blood pressure in humans, but the effects of animal protein intake on
      blood pressure have yet to be investigated. OBJECTIVE: We aimed to determine
      whether partial substitution of carbohydrate intake with animal protein intake
      from lean red meat changes blood pressure and other markers of cardiovascular
      disease risk in hypertensive persons. DESIGN: Hypertensive persons (n = 60) were
      recruited to an 8-wk parallel-design study. The participants were randomly
      assigned either to maintain their usual diet (control group) or to partially
      replace energy intake from carbohydrate-rich foods with protein from lean red
      meat (protein group). Measurements were performed at baseline and at the end of
      the intervention. RESULTS: Compared with the control group, the protein group had
      a significantly higher protein intake [x (95% CI) percent of energy: 5.3% (3.7%,
      6.9%), P < 0.001] and a corresponding lower carbohydrate intake [-5.3% of energy
      (-7.9%, -2.7%), P < 0.001]. Body weight and intakes of fat, alcohol, and fiber
      were not significantly different between the groups. Compared with the control
      group, the clinic, 24-h, awake, and asleep systolic blood pressures were lower [
      5.2 (-10.3, -0.1), -4.0 (-7.4, -0.6), -4.7 (-8.9, -0.5), and -4.7 (-10.3, -0.1)
      mm Hg, respectively, P < 0.05] and fasting plasma glucose concentrations were
      higher [0.33 mmol/L (0.09, 0.58 mmol/L), P = 0.008] in the protein group. These
      differences were independent of age, sex, and changes in weight, alcohol intake,
      or urinary sodium and potassium excretion. Diastolic blood pressure and heart
      rate, arterial compliance, blood lipids, and serum insulin were not significantly
      different between the groups. CONCLUSION: Within the context of other studies,
      these results suggest that modest substitution of carbohydrate-rich foods with
      protein-rich foods may lower blood pressure in hypertensive persons.

PMID- 16600929
TI  - Antenatal supplementation with micronutrients and biochemical indicators of
      status and subclinical infection in rural Nepal.
AB  - BACKGROUND: Previously we showed that women in rural Nepal experience multiple
      micronutrient deficiencies in early pregnancy. OBJECTIVE: This study examined the
      effects of daily antenatal micronutrient supplementation on changes in the
      biochemical status of several micronutrients during pregnancy. DESIGN: In Nepal,
      we conducted a randomized controlled trial in which 4 combinations of
      micronutrients (folic acid, folic acid + iron, folic acid + iron + zinc, and a
      multiple micronutrient supplement containing folic acid, iron, zinc, and 11 other
      nutrients) plus vitamin A, or vitamin A alone as a control, were given daily
      during pregnancy. In a subsample of subjects (n = 740), blood was collected both
      before supplementation and at approximately 32 wk of gestation. RESULTS: In the
      control group, serum concentrations of zinc, riboflavin, and vitamins B-12 and B
      6 decreased, whereas those of copper and alpha-tocopherol increased, from the
      first to the third trimester. Concentrations of serum folate, 25-hydroxyvitamin
      D, and undercarboxylated prothrombin remained unchanged. Supplementation with
      folic acid alone or folic acid + iron decreased folate deficiency. However, the
      addition of zinc failed to increase serum folate, which suggests a negative
      inhibition; multiple micronutrient supplementation increased serum folate. Folic
      acid + iron + zinc failed to improve zinc status but reduced subclinical
      infection. Multiple micronutrient supplementation decreased the prevalence of
      serum riboflavin, vitamin B-6, vitamin B-12, folate, and vitamin D deficiencies
      but had no effect on infection. CONCLUSIONS: In rural Nepal, antenatal
      supplementation with multiple micronutrients can ameliorate, to some extent, the
      burden of deficiency. The implications of such biochemical improvements in the
      absence of functional and health benefits remain unclear.

PMID- 16600930
TI  - Anthropometric predictors of body fat as measured by hydrostatic weighing in
      Guatemalan adults.
AB  - BACKGROUND: Most predictive equations currently used to assess percentage body
      fat (%BF) were derived from persons in industrialized Western societies.
      OBJECTIVE: We developed equations to predict %BF from anthropometric measurements
      in rural and urban Guatemalan adults. DESIGN: Body density was measured in 123
      women and 114 men by using hydrostatic weighing and simultaneous measurement of
      residual lung volume. Anthropometric measures included weight (in kg), height (in
      cm), 4 skinfold thicknesses [(STs) in mm], and 6 circumferences (in cm). Sex
      specific multiple linear regression models were developed with %BF as the
      dependent variable and age, residence (rural or urban), and all anthropometric
      measures as independent variables (the "full" model). A "simplified" model was
      developed by using age, residence, weight, height, and arm, abdominal, and calf
      circumferences as independent variables. RESULTS: The preferred full models were
      %BF = -80.261 - (weight x 0.623) + (height x 0.214) + (tricipital ST x 0.379) +
      (abdominal ST x 0.202) + (abdominal circumference x 0.940) + (thigh circumference
      x 0.316); root mean square error (RMSE) = 3.0; and pure error (PE) = 3.4 for men
      and %BF = -15.471 + (tricipital ST x 0.332) + (subscapular ST x 0.154) +
      (abdominal ST x 0.119) + (hip circumference x 0.356); RMSE = 2.4; and PE = 2.9
      for women. The preferred simplified models were %BF = -48.472 - (weight x 0.257)
      + (abdominal circumference x 0.989); RMSE = 3.8; and PE = 3.7 for men and %BF =
      19.420 + (weight x 0.385) - (height x 0.215) + (abdominal circumference x 0.265);
      RMSE = 3.5; and PE = 3.5 for women. CONCLUSION: These equations performed better
      in this developing-country population than did previously published equations.

PMID- 16600931
TI  - Carbohydrate balance predicts weight and fat gain in adults.
AB  - BACKGROUND: The prevention and treatment of obesity is a public health challenge.
      OBJECTIVE: We investigated the effects of dietary composition, insulin
      sensitivity (S(I)), and energy balance on predicted changes in body composition.
      DESIGN: In a randomized crossover design study, 39 normal-weight (n = 23),
      overweight (n = 8), and obese (n = 8) men and women (aged 25-36 y) each followed
      a 15-d isocaloric high-fat (HF; 50% fat) and high-carbohydrate [HC; 55%
      carbohydrate (CHO)] diet with a 4-6-wk washout period during the first year.
      During each treatment, energy balance was measured while the subjects were
      inactive by using indirect calorimetry on day 15, and S(I) was measured by using
      a euglycemic clamp study (40 mU . m(-2) . min(-1)) on day 16. Weight and body
      composition were then measured annually for 4 y. The outcomes for fat mass,
      percentage body fat, and weight were measured by using a linear 2-stage mixed
      model. RESULTS: CHO balance (day 15) and S(I) (day 16) on the HC diet were highly
      and significantly correlated (r = 0.55, P < 0.001). On the HC diet, the subjects
      who had a higher positive CHO balance (day 15) gained less fat mass (P < 0.001),
      percentage body fat (P = 0.006), and weight (P = 0.024) over time. When adjusted
      for S(I), CHO balance remained a significant predictor of changes in fat mass (P
      = 0.021) and percentage body fat (P = 0.025). CONCLUSIONS: On a HC diet, the
      subjects who had a higher positive CHO balance on day 15 while they were inactive
      gained less fat mass during 4 y, a predictive effect independent of S(I). As
      suggested in rodents, the capacity to expand the glycogen pool might reduce
      energy intake and protect against fat and weight gain.

PMID- 16600932
TI  - Validation of a 3-dimensional photonic scanner for the measurement of body
      volumes, dimensions, and percentage body fat.
AB  - BACKGROUND: The 3-dimensional photonic scan (3DPS) technique has been used during
      the past decade in the fashion industry and for epidemiologic surveys to estimate
      human body sizes. OBJECTIVE: The objective of the study was to validate the
      accuracy of a recently developed 3DPS (C9036-02; Hamamatsu Photonics KK,
      Hamamatsu, Japan) for the measurement of body volume, circumferences, lengths,
      and percentage body fat with the use of underwater weighing (UWW) and tape
      measures as criterion methods. DESIGN: Ninety-two subjects (44 females and 48
      males) aged 6-83 y and weighing 23-182 kg (52-400 lbs) participated in the study.
      The subjects were measured while they wore minimal clothing and a head cap.
      Similar measurements were performed on a mannequin with and without clothing
      RESULTS: All subjects were measured with 3DPS and a tape measure; 63 subjects
      underwent UWW and residual lung volume measurements. The values obtained with
      3DPS were slightly but significantly greater than those obtained with UWW for
      body volume (81.9 +/- 4.0 L compared with 81.5 +/- 4.0 L, P < 0.0001) and those
      obtained with a tape measure for circumferences (P < 0.001), but the values for
      percentage body fat were not significantly different between 3DPS and UWW (P =
      0.648). The values obtained with 3DPS were significantly greater than those
      obtained by UWW and a tape measure for the clothed mannequin, but the values were
      not uniformly significantly different for the mannequin without clothing.
      CONCLUSIONS: The 3DPS measures body volume, circumferences, and length rapidly
      and accurately. However, to generate an accurate total-body volume measurement
      with 3DPS to estimate percentage body fat, the subjects must wear close-fitting
      minimal clothing and be able to stand motionless for 10 s (normal scan mode)
      while holding their breath, which is done immediately after a maximum expiration.

PMID- 16600933
TI  - Colonic fermentation of indigestible carbohydrates contributes to the second-meal
      effect.
AB  - BACKGROUND: Low postprandial blood glucose is associated with low risk of
      metabolic diseases. A meal's ability to diminish the glucose response to
      carbohydrates eaten during the following meal is known as the "second-meal
      effect" (SME). The reduced glycemia elicited by low-glycemic-index (LGI) foods
      consumed during the first meal has been suggested as the main mechanism for SME.
      However, LGI foods often increase colonic fermentation because of the presence of
      fiber and resistant starch. OBJECTIVE: The objective was to study the SME of
      greater fermentation of high-glycemic-index (HGI) and LGI carbohydrates eaten
      during a previous meal. DESIGN: Ten healthy volunteers ate 3 breakfast test meals
      consisting of sponge cakes made with rapidly digestible, nonfermentable
      amylopectin starch plus cellulose (HGI meal), amylopectin starch plus the
      fermentable disaccharide lactulose (HGI-Lac meal), or slowly digestible, partly
      fermentable amylose starch plus cellulose (LGI meal). Five hours later, subjects
      were fed the same standard lunch containing 93 g available carbohydrates. Blood
      was collected for measurement of glucose, insulin, and nonesterified fatty acids
      (NEFAs). Breath hydrogen was measured as a marker of colonic fermentation.
      Postlunch gastric emptying was measured by using ultrasonography. RESULTS: Both
      the HGI-Lac and LGI meals improved glucose tolerance at lunch. In the case of the
      HGI-Lac meal, this effect was concomitant with low NEFA concentrations and
      delayed gastric emptying. CONCLUSION: Fermentable carbohydrates, independent of
      their effect on a food's glycemic index, have the potential to regulate
      postprandial responses to a second meal by reducing NEFA competition for glucose
      disposal and, to a minor extent, by affecting intestinal motility.

PMID- 16600934
TI  - Oral glutamine and amino acid supplementation inhibit whole-body protein
      degradation in children with Duchenne muscular dystrophy.
AB  - BACKGROUND: Glutamine has been shown to acutely decrease whole-body protein
      degradation in Duchenne muscular dystrophy (DMD). OBJECTIVE: To improve
      nutritional support in DMD, we tested whether oral supplementation with glutamine
      for 10 d decreased whole-body protein degradation significantly more than did an
      isonitrogenous amino acid control mixture. DESIGN: Twenty-six boys with DMD were
      included in this randomized, double-blind parallel study; they received an oral
      supplement of either glutamine (0.5 g . kg(-1) . d(-1)) or an isonitrogenous,
      nonspecific amino acid mixture (0.8 g . kg(-1) . d(-1)) for 10 d. The subjects in
      each group were not clinically different at entry. Leucine and glutamine
      metabolisms were estimated in the postabsorptive state by using a primed
      continuous intravenous infusion of [1-(13)C]leucine and [2-(15)N]glutamine before
      and 10 d after supplementation. RESULTS: A significant effect of time was
      observed on estimates of whole-body protein degradation. A significant (P < 0.05)
      decrease in the rate of leucine appearance (an index of whole-body protein
      degradation) was observed after both glutamine and isonitrogenous amino acid
      supplementation [x +/-SEM: 136 +/- 9 to 124 +/- 6 micromol . kg fat-free mass
      (FFM)(-1) . h(-1) for glutamine and 136 +/- 6 to 131 +/- 8 micromol . kg FFM(-1)
      . h(-1) for amino acids]. A significant (P < 0.05) decrease in endogenous
      glutamine due to protein breakdown was also observed (91 +/- 6 to 83 +/- 4
      micromol . kg FFM(-1) . h(-1) for glutamine and 91 +/- 4 to 88 +/- 5 micromol .
      kg FFM(-1) . h(-1) for amino acids). The decrease in the estimates of whole-body
      protein degradation did not differ significantly between the 2 supplemental
      groups. CONCLUSION: Oral glutamine or amino acid supplementation over 10 d
      equally inhibits whole-body protein degradation in DMD.

PMID- 16600935
TI  - Greater whole-body myofibrillar protein breakdown in cachectic patients with
      chronic obstructive pulmonary disease.
AB  - BACKGROUND: Experimental studies indicate that greater skeletal muscle protein
      breakdown is a trigger for the cachexia that often is prevalent in chronic
      obstructive pulmonary disease (COPD). OBJECTIVE: We compared myofibrillar protein
      breakdown (MPB) with whole-body (WB) protein breakdown (PB) in 9 cachectic COPD
      patients [x +/- SEM forced expiratory volume in 1 s (FEV(1)): 48 +/- 4% of
      predicted], 7 noncachectic COPD patients (FEV(1): 53 +/- 5% of predicted), and 7
      age-matched healthy control subjects, who were matched by body mass index with
      the noncachectic patients. DESIGN: After the subjects fasted overnight (10 h) and
      discontinued the maintenance medication, a primed constant and continuous
      infusion protocol was used to infuse L-[ring-(2)H(5)]-phenylalanine and L-[ring
      (2)H(2)]-tyrosine to measure WB protein turnover and L-[(2)H(3)]-3
      methylhistidine to measure WB MPB. Three arterialized venous blood samples were
      taken between 80 and 90 min of infusion to measure amino acid concentrations and
      tracer enrichments. RESULTS: Body composition, WB protein turnover, and WB MPB
      did not differ significantly between the noncachectic COPD and control subjects.
      Cachectic COPD patients had lower fat mass and fat-free mass values (both: P <
      0.01) than did the noncachectic COPD patients. WB MPB was significantly (P <
      0.05) higher in the cachectic COPD group (18 +/- 3 nmol . kg(-1) . min(-1)) than
      in the combined control and noncachectic COPD groups (10 +/- 1 nmol . kg(-1) .
      min(-1)), but WB protein turnover did not differ significantly between the
      groups. Correlations with fat-free mass were significant (P < 0.05) for plasma
      glutamate and branched-chain amino acids, and that for WB MPB trended toward
      significance (P = 0.07). CONCLUSION: Cachexia in clinically stable patients with
      moderate COPD is characterized by increased WB MPB, which indicates that
      myofibrillar protein wasting is an important target for nutritional and
      pharmacologic modulation.

PMID- 16600936
TI  - Chronic cigarette smoking is associated with diminished folate status, altered
      folate form distribution, and increased genetic damage in the buccal mucosa of
      healthy adults.
AB  - BACKGROUND: Smoking causes genetic damage in buccal cells and increases the risk
      of oral cancer. Because folate is instrumental in DNA synthesis and repair, it is
      a determinant of genetic stability and therefore might attenuate the genotoxic
      effects of smoking. OBJECTIVE: Our aim was to compare the presence of folate
      metabolites and select indicators of genetic damage in the mouths of chronic
      smokers and nonsmokers. DESIGN: Dietary, biochemical, and molecular correlates of
      folate status were measured in healthy smoker (n = 35) and nonsmoker (n = 21)
      groups of comparable age, sex, and body mass indexes. RESULTS: After correction
      for dietary intake, the smokers displayed lower plasma, erythrocyte, and buccal
      mucosal cell (BMC) folate (20%, 32%, and 50% lower, respectively; P < 0.05) and
      lower plasma vitamin B-12 and pyridoxal 5-phosphate (P < 0.05) than did
      nonsmokers. Folate in the BMCs of smokers comprised significantly greater
      proportions of pteroylmonoglutamate, formyltetrahydrofolate, and 5,10
      methenyltetrahyrofolate than did folate in the BMCs of nonsmokers. Although the
      degree of genomic methylation and uracil incorporation in the buccal cells of the
      2 groups were not significantly different, the BMC micronucleus index, a
      cytologic indicator of genetic damage, in the smokers was 2-fold that of the
      nonsmokers (9.57 compared with 4.44 micronuclei/1000 cells; P < 0.0001). Neither
      systemic nor oral folate status was an independent predictor of micronuclei.
      CONCLUSIONS: Chronic smoking is associated with a lower systemic status of
      several B vitamins, reduced oral folate, and changes in folate form distribution
      in the mouth. However, the cytologic damage that is evident in the mouths of
      smokers does not correlate with oral folate status.

PMID- 16600937
TI  - [6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in
      preventing a decline in blood folate concentrations during lactation.
AB  - BACKGROUND: Studies in nonpregnant, nonlactating women suggest that folate
      supplementation in the form of 5-methyltetrahydrofolate ([6S]-5-methylTHF) is at
      least as effective as folic acid in increasing blood folate indexes. No data,
      however, are available on the effect of supplemental [6S]-5-methylTHF on blood
      folate concentrations during lactation. OBJECTIVE: We assessed the relative
      effectiveness of [6S]-5-methylTHF, a placebo, and folic acid in maintaining blood
      folate indexes during lactation in a sample of healthy Canadian women consuming
      folic acid-fortified foods. DESIGN: This study was designed as a 16-wk,
      randomized, placebo-controlled intervention. Pregnant women (n = 72) advised to
      consume a folic acid-containing prenatal supplement (1000 microg/d) during
      pregnancy were enrolled at 36 wk gestation. After delivery, the women were
      randomly assigned to receive [6S]-5-methylTHF (416 microg/d, 906 nmol/d) or a
      placebo or were assigned to a folic acid (400 microg/d, 906 nmol/d) reference
      group. RESULTS: At 16 wk of lactation, the mean red blood cell (RBC) folate
      concentration in women in the [6S]-5-methylTHF group (2178; 95% CI: 1854, 2559
      nmol/L) was greater than that in the folic acid (1967; 1628, 2377 nmol/L; P <
      0.05) and placebo (1390; 1198, 1613 nmol/L; P < 0.002) groups after adjustment
      for baseline concentrations (36 wk gestation). The distribution of folate forms
      in RBCs did not differ significantly between the [6S]-5-methylTHF and placebo
      groups. However, the folic acid group had greater amounts of 5-formylTHF (P <
      0.03). CONCLUSION: [6S]-5-MethylTHF appeared to be as effective as, and perhaps
      more effective than, folic acid in preserving RBC folate concentrations during
      lactation.

PMID- 16600938
TI  - Effects of varied energy density of complementary foods on breast-milk intakes
      and total energy consumption by healthy, breastfed Bangladeshi children.
AB  - BACKGROUND: Information is needed to design studies of the effects of
      complementary feeding regimens on children's intakes of complementary foods (CFs)
      and breast milk. OBJECTIVE: We evaluated the effects of varied energy density of
      CFs on the time until stabilization of dietary intakes and on total daily energy
      intakes (EIs) and breast-milk intakes. DESIGN: CFs with low [0.4 kcal/g (LD)] and
      high [1.5 kcal/g (HD)] energy density were fed 3 times/d to 10 children (aged 9
      18 mo) during 2 randomly assigned sequences of three 8-d diet periods (HD-LD-HD
      or LD-HD-LD) along with ad libitum breastfeeding. CF and breast-milk intakes were
      measured. RESULTS: Intakes of the HD diet and breast milk did not vary by day of
      period, but intake of the LD diet increased progressively. During days 5-7 of the
      last 2 diet periods in each sequence, more of the LD than of the HD diet was
      consumed (752 +/- 252 and 439 +/- 111 g/d, respectively; P < 0.001), but EIs from
      CFs were greater with the HD diet. Breast-milk consumption was slightly less (192
      +/- 115 and 234 +/- 121 g/d, respectively; P = 0.03) but total daily EI was
      greater (774 +/- 175 and 441 +/- 85 kcal/d, respectively; P < 0.001) during the
      HD than during the LD diet period. CONCLUSIONS: New information on the effects of
      newly introduced diets on daily intakes of these diets and of breast milk can be
      used to design future studies. Total daily EIs were greater with the HD diet
      despite its negative effects on breast-milk intakes.

PMID- 16600939
TI  - Estimating the effects of energy imbalance on changes in body weight in children.
AB  - BACKGROUND: Estimating changes in weight from changes in energy balance is
      important for predicting the effect of obesity prevention interventions.
      OBJECTIVE: The objective was to develop and validate an equation for predicting
      the mean weight of a population of children in response to a change in total
      energy intake (TEI) or total energy expenditure (TEE). DESIGN: In 963 children
      with a mean (+/-SD) age of 8.1 +/- 2.8 y (range: 4-18 y) and weight of 31.5 +/-
      17.6 kg, TEE was measured by using doubly labeled water. Log weight (dependent
      variable) and log TEE (independent variable) were analyzed in a linear regression
      model with height, age, and sex as covariates. It was assumed that points of
      dynamic balance, called "settling points," occur for populations wherein energy
      is in balance (TEE = TEI), weight is stable (ignoring growth), and energy flux
      (EnFlux) equals TEE. RESULTS: TEE (or EnFlux) explained 74% of the variance in
      weight. The unstandardized regression coefficient was 0.45 (95% CI: 0.38, 0.51;
      R(2) = 0.86) after including covariates. Conversion into proportional changes
      (time(1) to time(2)) gave the equation (weight(2)/weight(1)) =
      (EnFlux(2)/EnFlux(1))(0.45). In 3 longitudinal studies (n = 212; mean follow-up
      of 3.4 y), the equation predicted the mean follow-up measured weight to within
      0.5%. CONCLUSIONS: The relation of EnFlux with weight was positive, which implied
      that a high TEI (rather than low physical activity and low TEE) was the main
      determinant of high body weight. Two populations of children with a 10%
      difference in mean EnFlux would have a 4.5% difference in mean weight.

PMID- 16600940
TI  - Pretreatment with Lactobacillus- and Bifidobacterium-containing yogurt can
      improve the efficacy of quadruple therapy in eradicating residual Helicobacter
      pylori infection after failed triple therapy.
AB  - BACKGROUND: Lactobacillus- and Bifidobacterium-containing yogurt (AB-yogurt) can
      suppress Helicobacter pylori. Improvement of the eradication rate by quadruple
      therapy of residual H. pylori after failed triple therapy is needed. OBJECTIVE:
      We tested whether prior treatment with AB-yogurt improved the efficacy of
      quadruple therapy in eradicating residual H. pylori after failed triple therapy.
      DESIGN: One hundred thirty-eight patients in whom triple therapy failed were
      enrolled for a culture study of H. pylori to assess antimicrobial resistance.
      These patients were then randomly assigned in equal numbers to either a yogurt
      plus-quadruple therapy group or a quadruple therapy-only group. The patients
      received 1 wk of quadruple therapy with or without a 4-wk pretreatment with AB
      yogurt (400 mL/d). In the yogurt-plus-quadruple group, excessive
      delta(13)CO(2)/mL values of the (13)C-urea breath test were collected before and
      every 2 wk during the 4-wk ingestion of yogurt. For both groups, a (13)C-urea
      breath test was conducted > or =6 wk after the quadruple therapy to assess the
      outcome of residual H. pylori eradication. RESULTS: For the patients in the
      yogurt-plus-quadruple therapy group infected with either antibiotic-sensitive or 
      resistant H. pylori, the excessive delta(13)CO(2)/mL values of the (13)C-urea
      breath test were significantly decreased after the 4-wk ingestion of AB-yogurt (P
      < 0.0001). The yogurt-plus-quadruple therapy group had a higher H. pylori
      eradication rate than did the quadruple therapy-only group (intention-to-treat
      analysis: 85% compared with 71.1%, P < 0.05; per-protocol analysis: 90.8%
      compared with 76.6%, P < 0.05). CONCLUSION: A 4-wk pretreatment with AB-yogurt
      can decrease H. pylori loads despite antimicrobial resistance, thus improving the
      efficacy of quadruple therapy in eradicating residual H. pylori.

PMID- 16600941
TI  - Vitamins C and E in adolescents and young adults with HIV infection.
AB  - BACKGROUND: Oxidative stress during HIV infection may impair immune function,
      cause more rapid disease progression, and increase requirements for dietary
      antioxidants such as vitamins C and E. OBJECTIVES: The study had 2 principal
      objectives. The first was to ascertain whether HIV infection and immune
      activation were associated with lower plasma concentrations of ascorbate, urate,
      and alpha- and gamma-tocopherols and with total antioxidant status (TAS). The
      second objective was to ascertain whether these antioxidants were associated with
      protection against oxidative damage. DESIGN: This was a cross-sectional study
      involving 241 HIV-positive and 115 HIV-negative subjects aged 14-23 y. Subjects
      were primarily female (76%) and African American (70%), and 21% were Hispanic.
      RESULTS: Plasma ascorbate was significantly lower, but gamma-tocopherol and TAS
      were significantly higher in subjects with HIV infection when the analysis was
      adjusted for dietary intake and sex. Plasma alpha-tocopherol did not differ
      significantly by HIV status. Plasma gamma-tocopherol also was higher in subjects
      with oxidative damage than in those without such damage. More than 90% of
      subjects had adequate plasma concentrations for both ascorbate and alpha
      tocopherol, although alpha-tocopherol concentrations were lower than expected on
      the basis of third National Health and Nutrition Examination Survey data.
      CONCLUSIONS: Low plasma ascorbate concentrations in HIV-positive subjects suggest
      that vitamin C requirements are significantly higher in those with HIV infection.
      Plasma tocopherol concentrations were not depressed by HIV infection and may be
      maintained by compensatory mechanisms such as the activity of alpha-tocopherol
      transfer protein.

PMID- 16600942
TI  - Dietary glycemic index and carbohydrate in relation to early age-related macular
      degeneration.
AB  - BACKGROUND: Several dietary factors have been linked to age-related maculopathy
      (ARM), the early form of age-related macular degeneration, and there is reason to
      think that dietary carbohydrate may play a role in the development of ARM.
      OBJECTIVE: The purpose of the present study was to examine the relation between
      dietary carbohydrate quality, as measured by dietary glycemic index (GI) or total
      carbohydrate intake, and ARM. DESIGN: From the Nurses' Health Study, 1036 eyes
      from 526 Boston-area participants without a previous ARM diagnosis were included
      in the present study. The presence and degree of ARM were classified by the Age
      Related Eye Diseases Study system. Long-term dietary information was based on
      data from an average of 4 food-frequency questionnaires collected over a 10-y
      period before the assessment of ARM. With eyes as the unit of analysis, we used a
      generalized estimating approach to logistic regression to estimate the odds
      ratios for ARM in a manner that accounted for the lack of independence between
      the 2 eyes from the same subject. RESULTS: After multivariate adjustment, dietary
      GI was related to ARM (specifically to retinal pigmentary abnormalities), whereas
      total carbohydrate intake was not. The odds ratio for ARM being in the highest
      tertile of dietary GI (> or =77.0) versus the lowest (<74.6) was 2.71 (95% CI:
      1.24, 5.93; P for trend = 0.01). Neither dietary GI nor total carbohydrate intake
      was related to drusen. CONCLUSION: Our results suggest that dietary GI may be an
      independent risk factor for ARM.

PMID- 16600943
TI  - Serum fatty acids as biomarkers of fat intake predict serum cholesterol
      concentrations in a population-based survey of New Zealand adolescents and
      adults.
AB  - BACKGROUND: The results of randomized controlled trials indicate that the amount
      and type of dietary fat are important predictors of serum cholesterol
      concentrations. However, the results of observational studies show weak or no
      association between dietary fat intake and serum cholesterol. Serum fatty acids
      are valid biomarkers of fat intake and may improve dietary estimates. OBJECTIVE:
      The objective was to ascertain whether serum fatty acids are associated with
      serum cholesterol concentrations in New Zealand adolescents and adults. DESIGN:
      The current study was a cross-sectional, national, population-based survey of
      2793 New Zealanders aged > or =15 y who participated in the 1997 National
      Nutrition Survey. The fatty acid composition of serum cholesterol esters,
      phospholipids, and triacylglycerols was measured. RESULTS: A 1-SD increase in
      myristic acid (14:0) in serum cholesterol ester, phospholipids, and
      triacylglycerol corresponded with increases in serum cholesterol of 0.19, 0.13,
      and 0.10 mmol/L, respectively, after adjustment of the regression analysis for
      sex, age, body mass index, ethnicity, and smoking. The mean difference in
      cholesterol concentrations between persons in the highest and the lowest
      quintiles of serum cholesteryl-myristate was 0.48 mmol/L (P for trend < 0.001). A
      1-SD increase in the proportion of linoleic acid (18:2n-6) in serum cholesterol
      ester, phospholipids, and triacylglycerol corresponded with decreases in serum
      cholesterol of 0.07, 0.07, and 0.05 mmol/L, respectively. The difference in mean
      serum cholesterol between the highest and lowest quintiles of cholesteryl
      linoleate was 0.18 mmol/L (P for trend = 0.019). CONCLUSION: Saturated and
      polyunsaturated fat intakes, measured by using fatty acid biomarkers, are
      important predictors of serum cholesterol concentrations in New Zealand.

PMID- 16600944
TI  - Folate intake, alcohol use, and postmenopausal breast cancer risk in the
      Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.
AB  - BACKGROUND: Several epidemiologic studies suggest that higher folate intakes are
      associated with lower breast cancer risk, particularly in women with moderate
      alcohol consumption. OBJECTIVE: We investigated the association between dietary
      folate, alcohol consumption, and postmenopausal breast cancer in women from the
      Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort. DESIGN:
      Dietary data were collected at study enrollment between 1993 and 2001. Folate
      content was assigned on the basis of prefortification (ie, pre-1998) databases.
      Of the 25 400 women participants with a baseline age of 55-74 y and with complete
      dietary and multivitamin information, 691 developed breast cancer between
      September 1993 and May 2003. We used Cox proportional hazard models with age as
      the underlying time metric to generate hazard ratios (HRs) and 95% CIs. RESULTS:
      The adjusted HRs were 1.19 (95% CI: 1.01, 1.41; P for trend = 0.04) for women
      reporting supplemental folic acid intake >/=400 mug/d compared with subjects
      reporting no supplemental intake. Comparison of the highest with the lowest
      quintile gave adjusted HRs of 1.04 (95% CI: 0.83, 1.31; P for trend = 0.56) and
      1.32 (95% CI: 1.04, 1.68; P for trend = 0.03) for food and total folate intake,
      respectively. Alcohol consumption was positively associated with breast cancer
      risk (highest compared with lowest quintile: HR = 1.37; 95% CI: 1.08, 1.76; P for
      trend = 0.02); the risk was greatest in women with lower total folate intake.
      CONCLUSIONS: Our results do not support the hypothesis that high folate intake
      reduces breast cancer risk; instead, they suggest that a high intake, generally
      attributable to supplemental folic acid, may increase the risk in postmenopausal
      women. However, our results confirm previous studies showing positive
      associations between moderate alcohol consumption and breast cancer.

PMID- 16600946
TI  - +9/+9 Homozygosity of the bradykinin receptor gene polymorphism is associated
      with reduced fat-free mass in chronic obstructive pulmonary disease.
AB  - BACKGROUND: The etiology of muscle wasting in chronic obstructive pulmonary
      disease (COPD) is incompletely understood. We previously showed that the D rather
      than the I polymorphic variant of the angiotensin-converting enzyme (ACE) gene is
      associated with preserved quadriceps strength in COPD. If the ACE D allele
      influences skeletal muscle through increased ACE-related kinin degradation [and
      reduced activity at the bradykinin type 2 receptor (BK(2)R)], we might expect a
      similar association with the +9 BK(2)R genotype in this population as well.
      OBJECTIVE: The objective was to test the hypothesis that the BK(2)R gene
      polymorphism is a determinant of fat-free mass and quadriceps strength in
      patients with COPD. DESIGN: In a cross-sectional design we determined BK(2)R
      genotype, fat-free mass, and quadriceps strength in 110 COPD patients with a mean
      (+/-SD) predicted forced expiratory volume in 1 s of 34.3 +/- 16.4% and in 104
      healthy age-matched control subjects. RESULTS: The mean (+/-SD) fat-free mass
      index (in kg/m(2)) was significantly lower in 37 patients homozygous for the +9
      allele than in carriers of the -9 allele (15.7 +/- 1.8 compared with 16.7 +/-
      2.3; P = 0.038); the same pattern was true for quadriceps maximal voluntary force
      (30.8 +/- 10.4 and 36.4 +/- 12.8 kg; P = 0.02), respectively. No significant
      effect of BK(2)R genotype on inspiratory muscle strength or on any variable in
      control subjects was observed. There was no interaction between the effect of the
      BK(2)R and ACE genotypes on quadriceps strength. CONCLUSIONS: The genotype
      associated with reduced BK(2)R expression is associated with reduced fat-free
      mass and quadriceps strength in COPD. However, alterations in the activity at the
      BK(2)R do not seem to account for the previously identified association of
      quadriceps strength with ACE genotype.

PMID- 16600945
TI  - Dietary choline and betaine assessed by food-frequency questionnaire in relation
      to plasma total homocysteine concentration in the Framingham Offspring Study.
AB  - BACKGROUND: Epidemiologic studies of choline and betaine intakes have been sparse
      because a food-composition database was not available until recently. The
      physiologic relevance of a variation in dietary choline and betaine in the
      general population and the validity of intake assessed by food-frequency
      questionnaire (FFQ) have not been evaluated. OBJECTIVE: This study was conducted
      to examine the physiologic relevance and validity of choline and betaine intakes
      measured by an FFQ. DESIGN: We examined the relations between choline and betaine
      intakes measured by FFQ and plasma total homocysteine (tHcy) concentrations in
      1960 participants from the Framingham Offspring Study. RESULTS: Higher intakes of
      dietary choline and betaine were related to lower tHcy concentrations independent
      of other determinants, including folate and other B vitamins. For the lowest and
      highest quintiles of dietary choline plus betaine, the multivariate geometric
      means for tHcy were 10.9 and 9.9 mumol/L (P for trend < 0.0001). The inverse
      association was manifested primarily in participants with low folate intakes (P
      for interaction < 0.0001). Among participants with folate intakes < or =250
      microg/d, the geometric mean tHcy concentrations in the lowest and highest
      quintiles of choline plus betaine intakes were 12.4 and 10.2 micromol/L (P for
      trend < 0.0001). Except for choline from phosphatidylcholine, individual forms of
      choline were inversely associated with tHcy concentrations. CONCLUSIONS: Our
      findings provide support for a physiologically important variation in choline and
      betaine intakes in the general population and for the validity of intake measured
      by FFQ.

PMID- 16600947
TI  - Suppressive effect of a selective increase in plasma linoleic acid concentration
      and intravascular lipolysis on peripheral T cell activation.

PMID- 16600948
TI  - Effect of nutritional manipulation on brain function: implications for future
      research.

PMID- 16600950
TI  - An evidence-based approach to medical nutrition education. Proceedings of a
      symposium held at Experimental Biology 2005, San Diego, California, USA, April 2,
      2005.

PMID- 16600949
TI  - Is the whole-diet approach better than a low-fat diet in cardiovascular risk
      reduction?

PMID- 16600951
TI  - The Nutrition Academic Award: brief history, overview, and legacy.
AB  - The Nutrition Academic Award (NAA) was developed by the National Heart, Lung, and
      Blood Institute with additional support from the National Institute of Diabetes
      and Digestive and Kidney Diseases. The purpose of the NAA was to formally
      integrate nutrition education within the medical school curriculum. Twenty-one
      medical schools were funded by the NAA in 2 waves of 5 y each, beginning in 1998
      for the 10 vanguard schools and ending in 2005 for the second wave. The
      organizational structure, goals, objectives, and results of the NAA are
      summarized. The overall strengths, challenges, and recommendations for future
      medical nutrition education efforts are also provided.

PMID- 16600953
TI  - Comprehensive integration of nutrition into medical training.
AB  - Nutrition must be integrated into the medical school curriculum to train
      physicians who can effectively provide nutrition care for the prevention and
      management of chronic diseases. This article describes the comprehensive
      nutrition curriculum developed at the University of Colorado School of Medicine.
      Two fundamental principles have guided the school's approach to medical nutrition
      education: 1) nutrition content must be broad in nature and be vertically
      integrated across the preclinical and clinical years and continued through
      postgraduate training, and 2) active adult learning (eg, "learning by doing")
      should be practiced whenever possible. From our experience, we have identified
      several key elements important for the successful integration of nutrition into
      the curriculum. First, identifying a core group of committed faculty to advocate
      for nutrition and serve as role models and having a physician nutrition
      specialist at the helm provides constant momentum for the advancement of
      nutrition education. Second, establishing a network of linkages with other
      elements of the existing curriculum creates the opportunity to add nutrition
      content without necessarily adding time. The third key element is an emphasis on
      incorporating nutrition in clinical training. Students must be routinely exposed
      to physicians practicing nutrition for nutrition to become part of standard
      patient care. This can be accomplished through multiple exposures to nutrition
      throughout the curriculum (ie, vertical integration). Finally, a coordinator is
      needed to monitor the many "fronts" of the integrated nutrition curriculum and to
      continue networking and program implementation.

PMID- 16600952
TI  - Status of nutrition education in medical schools.
AB  - BACKGROUND: Numerous entreaties have been made over the past 2 decades to improve
      the nutrition knowledge and skills of medical students and physicians. However,
      most graduating medical students continue to rate their nutrition preparation as
      inadequate. OBJECTIVE: The objective was to determine the amount and type of
      nutrition instruction at US medical schools, especially including the instruction
      that occurs outside designated nutrition courses. DESIGN: A 12-item survey asked
      nutrition educators to characterize nutrition instruction at their medical
      schools (required, optional, or not offered) and to quantify nutrition contact
      hours occurring both inside and outside designated nutrition courses. During
      2004, we surveyed all 126 US medical schools accredited at that time. RESULTS: A
      total of 106 surveys were returned for a response rate of 84%. Ninety-nine of the
      106 schools responding required some form of nutrition education; however, only
      32 schools (30%) required a separate nutrition course. On average, students
      received 23.9 contact hours of nutrition instruction during medical school
      (range: 2-70 h). Only 40 schools required the minimum 25 h recommended by the
      National Academy of Sciences. Most instructors (88%) expressed the need for
      additional nutrition instruction at their institutions. CONCLUSION: With the move
      to a more integrated curriculum and problem-based learning at many medical
      schools, a substantial portion of the total nutrition instruction is occurring
      outside courses specifically dedicated to nutrition. The amount of nutrition
      education in medical schools remains inadequate.

PMID- 16600954
TI  - Web-based resources for medical nutrition education.
AB  - The World Wide Web is a valuable source of nutrition and health information, but
      the time and effort required to take advantage of this resource may stand in the
      way of routine use in medical education and practice. The Nutrition Academic
      Award (NAA) has produced numerous examples of Web-based nutrition resources,
      including nutrition assessment tools, patient education materials, and
      presentations and curricula for professional education. The University of
      Wisconsin Medical Nutrition Handbook provides evidence-based nutrition care
      guides for common clinical problems, including obesity, diabetes, hypertension,
      lipid disorders, and the metabolic syndrome. Incorporation of these resources
      into medical practice may increase the provision of effective nutrition care.

PMID- 16600955
TI  - The evolution of Nutrition in Medicine, a computer-assisted nutrition curriculum.
AB  - The primary mission of the Nutrition in Medicine (NIM) project is to provide
      tools to facilitate the nutrition training of undergraduate medical students. NIM
      has developed and distributed a CD-ROM-based nutrition curriculum to medical
      schools since 1995. However, the medical school environment is changing rapidly;
      there is pressure to do more in less time, and many schools are emphasizing
      independent and integrated learning. The need for a nutrition curriculum that is
      more flexible and more accessible has driven the evolution of the NIM curriculum
      from CD-ROM-based delivery into a more modular curriculum with Web delivery. Such
      changes facilitate access and eliminate the need for installation of CD-ROMs and
      the associated technical support issues. In addition, the instructional units are
      smaller and more modular. Eventually, the authoring system will allow instructors
      to put together a course to meet their specific instructional needs. Our future
      plans also include custom-tailoring that will allow students to opt out of
      learning material on the basis of pretest scores if they are already proficient
      in the content. In this update, we provide a detailed description of the new
      system and the rationale for the modifications we made. Furthermore, we describe
      how each change addresses barriers to nutrition education as identified from our
      surveys and others and from direct user feedback. These innovative strategies
      should allow a better fit of NIM within diverse medical school environments and
      help to promote incorporation of the curriculum into more medical schools.

PMID- 16600956
TI  - Medical nutrition: a comprehensive, school-wide curriculum review.
AB  - BACKGROUND: A school-wide nutrition program was established in 1982 and a
      required medical nutrition course (MNC) was established in 1985 at the University
      of Nevada School of Medicine. Emphasis was placed on developing an integrated
      curriculum and on using innovative methods to incorporate nutrition into the
      existing curriculum. OBJECTIVE: The objective of this review was to establish a
      baseline and make positive curricular changes to comply with the recommendations
      of the Liaison Committee on Medical Education for accreditation. The MNC and the
      nutrition curriculum were evaluated as part of this 3-y comprehensive, school
      wide evaluation process. DESIGN: The MNC was invited for review (December 2004)
      because of its position in the curriculum (first year), special content and
      methods, and relation to other courses. A review team, which consisted of the
      Assistant Dean for Medical Education (who chaired the team), a curriculum
      coordinator, faculty representatives, and a medical student, was appointed. The
      MNC coordinator prepared a review book that included the requested documentation.
      The initial 3-h review meeting culminated in a formal evaluation and
      recommendations. Follow-up meetings at 1 mo and 1 y were scheduled. RESULTS: The
      review was a positive process that reaffirmed the uniqueness of the nutrition
      program at the University. It supported the MNC as an important part of the
      required curriculum. Recommendations included use of the Web, encouragement to
      identify new opportunities with interested faculty, and a structure to further
      integrate and align nutrition into existing courses. CONCLUSIONS: A positive,
      proactive review process supports the importance of nutrition in the medical
      school curriculum and encourages further integration.

PMID- 16600957
TI  - Lessons learned from nutrition curricular enhancements.
AB  - The Nutrition Academic Award funded 21 US medical schools to develop, implement,
      evaluate, and disseminate nutrition curricula for medical students, residents,
      and physicians in practice over a 5-y period. This article summarizes some of the
      important lessons learned from this process and offers guidance and strategies
      for long-term success of nutrition curricular enhancements. Medical educators
      need to continue to develop, implement, evaluate, and disseminate nutrition
      curricula with and without funding. By using the lessons learned and the products
      developed by the Nutrition Academic Award schools, educators will be in a
      position to enhance their medical curriculum.

PMID- 16600958
TI  - Nutrition Academic Award: nutrition education in graduate medical education.
AB  - The Nutrition Academic Award received by Tufts University School of Medicine
      strengthened our first-year Nutrition and Medicine course and clearly resulted in
      more nutrition in third-year clerkships and residency programs. Standardized
      patient cases in nutrition counseling for cardiovascular disease and weight loss
      were developed and incorporated into the clerkships and residency programs in
      internal medicine and family medicine. This was a value-added benefit that
      provided practice in initiating lifestyle changes and motivational skills, while
      expanding nutrition education. Eight standardized patient educators were trained
      in collaboration with physicians in internal and family medicine. Six slide shows
      on nutrition topics, 1-2 h each, were developed and included clinical cases,
      dietary analysis, and patient handouts. The Medicine Clerkship included 4
      nutrition sessions and the standardized patient experience, whereas the Family
      Medicine Clerkship included 1 nutrition session and the standardized patient
      experience. Working with faculty in the Department of Family Medicine, we
      developed a nutrition mentoring program for the family medicine residents and
      used 3 nutrition messages that were a modification of the Dietary Approaches to
      Stop Hypertension (DASH) diet to teach diet evaluation, intervention strategies,
      feedback from nutrition referrals, and follow-up. Seven sessions on nutrition and
      chronic disease with cases were offered to the residents in family medicine,
      which concluded with a nutrition intervention session using standardized patient
      educators. This expanded nutrition program in internal and family medicine along
      with the standardized patient experience receives excellent ratings from
      physicians, residents, and medical students.

PMID- 16600959
TI  - How can nutrition education contribute to competency-based resident evaluation?
AB  - The Curriculum Committee of the Nutrition Academic Award (NAA) has created a
      consensus document of knowledge, skills, and attitude learning objectives for
      medical nutrition education. To evaluate the impact of nutrition education in
      residency training, it is necessary to specify the goals and objectives of that
      education in terms of specific learner outcomes. To make the NAA objectives more
      user friendly for graduate medical education faculty, they must be translated
      into measurable competencies. The Accreditation Council for Graduate Medical
      Education has proposed a schema for organizing resident competencies. This
      article illustrates one way that the NAA curriculum objectives can be translated
      into specific competencies to demonstrate medical knowledge, patient care,
      practice-based learning, interpersonal and communication skills, professionalism,
      and systems-based practice.

PMID- 16600960
TI  - Continuing Medical Education in nutrition.
AB  - Surveys show that practicing physicians believe that nutrition is important in
      the care of their patients but feel inadequately trained to provide optimal
      nutrition counseling. Even if they receive good training in the preclinical
      years, the interest and enthusiasm of medical students for nutrition assessment
      and counseling rapidly diminishes if they do not receive reinforcement from their
      clinical house officers and faculty mentors. Continuing Medical Education (CME)
      in the area of nutrition is therefore essential for both practicing physicians
      and faculty teaching in medical schools or residency programs. This article
      provides examples of the types and formats of current CME offerings in nutrition
      and obesity care, describes the strengths and weaknesses of various CME programs
      available, and offers recommendations for the development of future CME curricula
      in the areas of nutrition and obesity.

PMID- 16600961
TI  - Training and certifying Physician Nutrition Specialists: the American Board of
      Physician Nutrition Specialists (ABPNS).
AB  - A significant obstacle to nutrition literacy among physicians is a paucity of
      Physician Nutrition Specialists (PNSs) on medical school faculties who can
      effectively advocate for change in medical school and residency curricula and who
      can serve as role models for incorporating nutrition into patient care. To
      address these issues, the Intersociety Professional Nutrition Education
      Consortium developed a paradigm for PNSs that is designed attract more physicians
      into the field; promulgated educational standards for fellowship training of
      PNSs; and established a unified mechanism for certifying PNSs, the American Board
      of Physician Nutrition Specialists (ABPNS). This article details the consensus
      paradigm and specific training standards and outlines the features and history of
      the ABPNS. The ABPNS certificate is intended to be the premier comprehensive
      credential for physicians who wish to identify nutrition as an area of expertise.
      Certification is equally accessible to physicians with backgrounds in any of the
      specialties relevant to clinical nutrition. It is hoped that more physicians will
      identify nutrition as a specialty interest if training opportunities are
      available in a variety of settings and are merged with their other professional
      interests. ABPNS invites input and feedback from colleagues around the world.

PMID- 16600962
TI  - Rapid peptide-based screening on the substrate specificity of severe acute
      respiratory syndrome (SARS) coronavirus 3C-like protease by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease
      (3CL(pro)) mediates extensive proteolytic processing of replicase polyproteins,
      and is considered a promising target for anti-SARS drug development. Here we
      present a rapid and high-throughput screening method to study the substrate
      specificity of SARS-CoV 3CL(pro). Six target amino acid positions flanking the
      SARS-CoV 3CL(pro) cleavage site were investigated. Each batch of mixed peptide
      substrates with defined amino acid substitutions at the target amino acid
      position was synthesized via the "cartridge replacement" approach and was
      subjected to enzymatic cleavage by recombinant SARS-CoV 3CL(pro). Susceptibility
      of each peptide substrate to SARS-CoV 3CL(pro) cleavage was monitored
      simultaneously by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS). The hydrophobic pocket in the P2 position at the
      protease cleavage site is crucial to SARS-CoV 3CL(pro)-specific binding, which is
      limited to substitution by hydrophobic residue. The binding interface of SARS-CoV
      3CL(pro) that is facing the P1' position is suggested to be occupied by acidic
      amino acids, thus the P1' position is intolerant to acidic residue substitution,
      owing to electrostatic repulsion. Steric hindrance caused by some bulky or beta
      branching amino acids in P3 and P2' positions may also hinder the binding of SARS
      CoV 3CL(pro). This study generates a comprehensive overview of SARS-CoV 3CL(pro)
      substrate specificity, which serves as the design basis of synthetic peptide
      based SARS-CoV 3CL(pro) inhibitors. Our experimental approach is believed to be
      widely applicable for investigating the substrate specificity of other proteases
      in a rapid and high-throughput manner that is compatible for future automated
      analysis.

PMID- 16600963
TI  - Directed evolution of human T cell receptor CDR2 residues by phage display
      dramatically enhances affinity for cognate peptide-MHC without increasing
      apparent cross-reactivity.
AB  - The mammalian alpha/beta T cell receptor (TCR) repertoire plays a pivotal role in
      adaptive immunity by recognizing short, processed, peptide antigens bound in the
      context of a highly diverse family of cell-surface major histocompatibility
      complexes (pMHCs). Despite the extensive TCR-MHC interaction surface, peptide
      independent cross-reactivity of native TCRs is generally avoided through cell
      mediated selection of molecules with low inherent affinity for MHC. Here we show
      that, contrary to expectations, the germ line-encoded complementarity determining
      regions (CDRs) of human TCRs, namely the CDR2s, which appear to contact only the
      MHC surface and not the bound peptide, can be engineered to yield soluble low
      nanomolar affinity ligands that retain a surprisingly high degree of specificity
      for the cognate pMHC target. Structural investigation of one such CDR2 mutant
      implicates shape complementarity of the mutant CDR2 contact interfaces as being a
      key determinant of the increased affinity. Our results suggest that manipulation
      of germ line CDR2 loops may provide a useful route to the production of high
      affinity TCRs with therapeutic and diagnostic potential.

PMID- 16600964
TI  - Conformational changes of the glucocorticoid receptor ligand binding domain
      induced by ligand and cofactor binding, and the location of cofactor binding
      sites determined by hydrogen/deuterium exchange mass spectrometry.
AB  - HXMS (hydrogen/deuterium exchange mass spectrometry) of the glucocorticoid
      receptor ligand-binding domain (GR LBD) complexed with the agonist dexamethasone
      and the antagonist RU-486 is described. Variations in the rates of exchange were
      observed in regions consistent with the published crystal structures of GR LBD
      complexed with RU-486 when compared with the GR dexamethasone complex. We also
      report the HXMS results for agonist-bound GR LBD with the coactivator
      transcriptional intermediary factor 2 (TIF2) and anatagonist-bound GR LBD with
      nuclear receptor corepressor (NCoR). Alterations in exchange rates observed for
      agonist-bound GR LBD with TIF2 present were consistent with the published crystal
      structural contacts for the complex. Alterations in exchange rates observed for
      antagonist-bound GR LBD with NCoR were a subset of those observed with TIF2
      binding, suggesting a common or overlapping binding site for coactivator and
      corepressor.

PMID- 16600965
TI  - Exploring protein interfaces with a general photochemical reagent.
AB  - Protein folding, natural conformational changes, or interaction between partners
      involved in recognition phenomena brings about differences in the solvent
      accessible surface area (SASA) of the polypeptide chain. This primary event can
      be monitored by the differential chemical reactivity of functional groups along
      the protein sequence. Diazirine (DZN), a photoreactive gas similar in size to
      water, generates methylene carbene (:CH(2)). The extreme chemical reactivity of
      this species allows the almost instantaneous and indiscriminate modification of
      its immediate molecular cage. (3)H-DZN was successfully used in our laboratory
      for studying protein structure and folding. Here we address for the first time
      the usefulness of this probe to examine the area of interaction in protein
      protein complexes. For this purpose we chose the complex formed between hen egg
      white lysozyme (HEWL) and the monoclonal antibody IgG(1) D1.3. :CH(2) labeling of
      free HEWL or complexed with IgG(1) D1.3 yields 2.76 and 2.32 mmol CH(2) per mole
      protein at 1 mM DZN concentration, respectively. This reduction (15%) becomes
      consistent with the expected decrement in the SASA of HEWL occurring upon
      complexation derived from crystallographic data (11%), in agreement with the
      known unspecific surface labeling reaction of :CH(2). Further comparative
      analysis at the level of tryptic peptides led to the identification of the sites
      involved in the interaction. Remarkably, those peptides implicated in the contact
      area show the highest differential labeling: H(15)GLDNYR(21),
      G(117)TDVQAWIR(125), andG(22)YSLGNWVCAAK(33). Thus, protein footprinting with DZN
      emerges as a feasible methodology useful for mapping contact regions of protein
      domains involved in macromolecular assemblies.

PMID- 16600966
TI  - New approaches to high-throughput structure characterization of SH3 complexes:
      the example of Myosin-3 and Myosin-5 SH3 domains from S. cerevisiae.
AB  - SH3 domains are small protein modules that are involved in protein-protein
      interactions in several essential metabolic pathways. The availability of the
      complete genome and the limited number of clearly identifiable SH3 domains make
      the yeast Saccharomyces cerevisae an ideal proteomic-based model system to
      investigate the structural rules dictating the SH3-mediated protein interactions
      and to develop new tools to assist these studies. In the present work, we have
      determined the solution structure of the SH3 domain from Myo3 and modeled by
      homology that of the highly homologous Myo5, two myosins implicated in actin
      polymerization. We have then implemented an integrated approach that makes use of
      experimental and computational methods to characterize their binding properties.
      While accommodating their targets in the classical groove, the two domains have
      selectivity in both orientation and sequence specificity of the target peptides.
      From our study, we propose a consensus sequence that may provide a useful
      guideline to identify new natural partners and suggest a strategy of more general
      applicability that may be of use in other structural proteomic studies.

PMID- 16600967
TI  - A comparative study of available software for high-accuracy homology modeling:
      from sequence alignments to structural models.
AB  - An open question in protein homology modeling is, how well do current modeling
      packages satisfy the dual criteria of quality of results and practical ease of
      use? To address this question objectively, we examined homology-built models of a
      variety of therapeutically relevant proteins. The sequence identities across
      these proteins range from 19% to 76%. A novel metric, the difference alignment
      index (DAI), is developed to aid in quantifying the quality of local sequence
      alignments. The DAI is also used to construct the relative sequence alignment
      (RSA), a new representation of global sequence alignment that facilitates
      comparison of sequence alignments from different methods. Comparisons of the
      sequence alignments in terms of the RSA and alignment methodologies are made to
      better understand the advantages and caveats of each method. All sequence
      alignments and corresponding 3D models are compared to their respective structure
      based alignments and crystal structures. A variety of protein modeling software
      was used. We find that at sequence identities >40%, all packages give similar
      (and satisfactory) results; at lower sequence identities (<25%), the sequence
      alignments generated by Profit and Prime, which incorporate structural
      information in their sequence alignment, stand out from the rest. Moreover, the
      model generated by Prime in this low sequence identity region is noted to be
      superior to the rest. Additionally, we note that DSModeler and MOE, which
      generate reasonable models for sequence identities >25%, are significantly more
      functional and easier to use when compared with the other structure-building
      software.

PMID- 16600968
TI  - Bacterial display using circularly permuted outer membrane protein OmpX yields
      high affinity peptide ligands.
AB  - A bacterial display methodology was developed for N- and C-terminal display and
      demonstrated to enable rapid screening of very large peptide libraries with high
      precision and efficiency. To overcome limitations of insertional fusion display
      libraries, a new scaffold was developed through circular permutation of the
      Escherichia coli outer membrane protein OmpX that presents both N and C termini
      on the external cell surface. Circularly permuted OmpX (CPX) display was directly
      compared to insertional fusion display by screening comparable peptide libraries
      in each format using magnetic and fluorescence activated cell sorting. CPX
      display enabled in situ measurement of dissociation rate constants with improved
      accuracy and, consequently, improved affinity discrimination during screening and
      ranking of isolated clones. Using streptavidin as a model target, bacterial
      display yielded the well-characterized HP(Q)/(M) motif obtained previously using
      several alternative peptide display systems, as well as three additional motifs
      (L(I)/(V) CQNVCY, CGWMY(F)/(Y)xEC, ERCWYVMHWPCNA). Using CPX display, a very high
      affinity streptavidin-binding peptide was isolated having a dissociation rate
      constant k(off) = 0.002sec(-1) even after grafting to the C terminus of an
      unrelated protein. Comparison of individual clones obtained from insertional
      fusion and terminal fusion libraries suggests that the N-terminal display yields
      sequences with greater diversity, affinity, and modularity. CPX bacterial display
      thus provides a highly effective method for screening peptide libraries to
      rapidly generate ligands with high affinity and specificity.

PMID- 16600969
TI  - Guanidinium derivatives bind preferentially and trigger long-distance
      conformational changes in an engineered T4 lysozyme.
AB  - The binding of guanidinium ion has been shown to promote a large-scale
      translation of a tandemly duplicated helix in an engineered mutant of T4
      lysozyme. The guanidinium ion acts as a surrogate for the guanidino group of an
      arginine side chain. Here we determine whether methyl- and ethylguanidinium
      provide better mimics. The results show that addition of the hydrophobic moieties
      to the ligand enhances the binding affinity concomitant with reduction in ligand
      solubility. Crystallographic analysis confirms that binding of the alternative
      ligands to the engineered site still drives the large-scale conformational
      change. Thermal analysis and NMR data show, in comparison to guanidinium, an
      increase in protein stability and in ligand affinity. This is presumably due to
      the successive increase in hydrophobicity in going from guanidinium to
      ethylguanidinium. A fluorescence-based optical method was developed to sense the
      ligand-triggered helix translation in solution. The results are a first step in
      the de novo design of a molecular switch that is not related to the normal
      function of the protein.

PMID- 16600970
TI  - Assessing the role of aromatic residues in the amyloid aggregation of human
      muscle acylphosphatase.
AB  - Among the many parameters that have been proposed to promote amyloid fibril
      formation is the pi-stacking of aromatic residues. We have studied the amyloid
      aggregation of several mutants of human muscle acylphosphatase in which an
      aromatic residue was substituted with a non-aromatic one. The aggregation rate
      was determined using the Thioflavin T test under conditions in which the variants
      populated initially an ensemble of partially unfolded conformations.
      Substitutions in aggregation-promoting fragments of the sequence result in a
      dramatically decreased aggregation rate of the protein, confirming the propensity
      of aromatic residues to promote this process. Nevertheless, a statistical
      analysis shows that the measured decrease of aggregation rate following mutation
      arises predominantly from a reduction of hydrophobicity and intrinsic beta-sheet
      propensity. This suggests that aromatic residues favor aggregation because of
      these factors rather than for their aromaticity.

PMID- 16600971
TI  - Thermodynamics of unfolding of an integral membrane protein in mixed micelles.
AB  - Quantitative studies of membrane protein folding and unfolding can be difficult
      because of difficulties with efficient refolding as well as a pronounced
      propensity to aggregate. However, mixed micelles, consisting of the anionic
      detergent sodium dodecyl sulfate and the nonionic detergent dodecyl maltoside
      facilitate reversible and quantitative unfolding and refolding. The 4
      transmembrane helix protein DsbB from the inner membrane of Escherichia coli
      unfolds in mixed micelles according to a three-state mechanism involving an
      unfolding intermediate I. The temperature dependence of the kinetics of this
      reaction between 15 degrees and 45 degrees C supports that unfolding from I to
      the denatured state D is accompanied by a significant decrease in heat capacity.
      For water-soluble proteins, the heat capacity increases upon unfolding, and this
      is generally interpreted as the increased binding of water to the protein as it
      unfolds, exposing more surface area. The decrease in DsbB's heat capacity upon
      unfolding is confirmed by independent thermal scans. The decrease in heat
      capacity is not an artifact of the use of mixed micelles, since the water soluble
      protein S6 shows conventional heat-capacity changes in detergent. We speculate
      that it reflects the binding of SDS to parts of DsbB that are solvent-exposed in
      the native DM-bound state. This implies that the periplasmic loops of DsbB are
      relatively unstructured. This anomalous thermodynamic behavior has not been
      observed for beta-barrel membrane proteins, probably because they do not bind SDS
      so extensively. Thus the thermodynamic behavior of membrane proteins appears to
      be intimately connected to their detergent-binding properties.

PMID- 16600972
TI  - The crystal structure of YycH involved in the regulation of the essential YycFG
      two-component system in Bacillus subtilis reveals a novel tertiary structure.
AB  - The Bacillus subtilis YycFG two-component signal transduction system is essential
      for cell viability, and the YycH protein is part of the regulatory circuit that
      controls its activity. The crystal structure of YycH was solved by two-wavelength
      selenium anomalous dispersion data, and was refined using 2.3 A data to an R
      factor of 25.2%. The molecule is made up of three domains, and has a novel three
      dimensional structure. The N-terminal domain features a calcium binding site and
      the central domain contains two conserved loop regions.

PMID- 16600975
TI  - Biweekly pegylated liposomal doxorubicin in patients with relapsed ovarian
      cancer: results of a multicenter phase-II trial.
AB  - BACKGROUND: The obvious benefit of pegylated liposomal doxorubicin (PLD) for
      tumour control in recurrent ovarian cancer is frequently offset by severe palmar
      plantar erythrodysesthesia (PPE). There is evidence that dose reduction from 50
      to 40 mg/m(2) reduces the incidence of PPE without compromising cytotoxic
      activity. We set out to investigate whether biweekly application further improves
      the therapeutic index of PLD. PATIENTS AND METHODS: Patients with recurrent
      ovarian cancer after surgery and adjuvant chemotherapy with platinum and taxane
      compounds were eligible to participate in this multi-institutional phase II
      study. PLD was administered at a dose of 20 mg/m(2) every two weeks. Eligible
      patients had ECOG performance status of < or =2, and sufficient organ function.
      We employed an optimized two-stage design to test the hypothesis that biweekly
      application of PLD reduces the frequency of grade III and IV PPE from 25% to 10%.
      Response and survival were addressed descriptively. RESULTS: Between October 2001
      and February 2004, 64 patients with median age of 59 (range 38-81) years were
      recruited onto this trial. We evaluated 553 (median 7, range 1-25) courses of PLD
      treatment. Most patients were in their third or fourth line of chemotherapy. PPE
      was noted in 30 patients (47.6%), but only three participants progressed to grade
      3 severity (4.7%, 95% confidence interval 1.0-13.1%). Partial response, stable
      disease, and tumour progression were observed in 5, 13, and 24 patients,
      respectively. Median overall and progression-free survival were 18.2 (range, 1.4
      34.0) and 4.3 (range 0.5-22.3) months. CONCLUSIONS: Biweekly PLD may reduce the
      incidence of PPE while retaining efficacy in relapsed ovarian cancer. Our data
      support the need for a randomized trial to strengthen these assumptions.

PMID- 16600976
TI  - Insulin-like growth factor receptor 1 (IGFR-1) is significantly associated with
      longer survival in non-small-cell lung cancer patients treated with gefitinib.
AB  - BACKGROUND: The aim of the study was to assess whether loss of PTEN and
      expression of insulin-like growth factor receptor 1 (IGFR-1) could be responsible
      for intrinsic resistance to the tyrosine kinase inhibitor (TKI) gefitinib.
      PATIENTS AND METHODS: One hundred and twenty-four gefitinib-treated patients with
      advanced non-small-cell lung cancer (NSCLC) were analyzed for PTEN and IGFR-1
      expression by immunohistochemistry. RESULTS: IGFR-1 was evaluated in 77 patients
      and resulted positive in 30 (39.0%). IGFR-1 expression was not significantly
      associated with clinical or biological characteristics. No difference in response
      to gefitinib treatment (16.7% versus 12.8%, P = 0.74) and time to progression
      (2.6 versus 3.06 months, P = 0.83) was observed between IGFR-1+ and IGFR-1-.
      Median survival was significantly longer in IGFR-1+ patients (17.8 versus 7.3
      months, P = 0.013). PTEN expression was successfully evaluated in 93 cases. Loss
      of PTEN was detected in 19 tumors (20.4%) and was not associated with any
      clinical or biological characteristic. No difference in terms of response, time
      to progression and survival was observed between PTEN+ and PTEN- patients. In
      multivariable analysis IGFR-1 negative status was significantly associated with
      higher risk of death (hazard ratio 2.21, P = 0.012). CONCLUSIONS: IGFR-1
      expression and loss of PTEN are not associated with intrinsic resistance to
      gefitinib. Clinical relevance of these two biomarkers as determinant for acquired
      resistance, and the prognostic role of IGFR-1 expression in patients not exposed
      to TKIs should be evaluated further.

PMID- 16600977
TI  - Vascular endothelial growth factor 936 C/T polymorphism in cancer patients.

PMID- 16600978
TI  - Tumour stem cell-targeted treatment: elimination or differentiation.
AB  - A wide range of studies suggest that most cancers are clonal and may represent
      the progeny of a single cell, a cancer stem cell (CSC) endowed with the capacity
      to maintain tumour growth. The concept of a cancer stem cell emerged decades ago,
      and the haematopoietic system is where it has mostly gained ground. More
      recently, CSC have been described in breast cancer and brain tumours. Growing
      evidence suggests that pathways regulating normal stem cell self-renewal and
      differentiation are also present in cancer cells and CSC. Malignant tumours can
      be viewed as an abnormal organ in which a small population of tumourigenic cancer
      stem cells have escaped the normal limits of self-renewal giving rise to
      abnormally differentiated cancer cells that contribute to tumour progression and
      growth. This new model has important implications for the study and treatment of
      cancer. Understanding the molecular circuitry which contributes to the
      maintenance of stem cells may provide an insight into the molecular mechanisms of
      cancer and thus new approaches for elimination or differentiation therapy.
      Therapies targeting CSC should focus on pathways such as Wnt, Shh and Notch which
      are required for the maintenance of cancer stem cells, but also on the ABC
      transporter family and other specific properties of cancer stem cells.

PMID- 16600979
TI  - Vaccination of colorectal cancer patients with CEA-loaded dendritic cells:
      antigen-specific T cell responses in DTH skin tests.
AB  - BACKGROUND: Dendritic cells (DCs) are the professional antigen-presenting cells
      of the immune system. As such they are currently used in clinical vaccination
      protocols in cancer patients. PATIENTS AND METHODS: We evaluated the ability of
      mature DCs pulsed with carcinoembryonic antigen (CEA)-peptide to induce CEA
      specific T cell responses in patients with resectable liver metastases from
      colorectal cancer. CEA-specific T cell reactivity was monitored in peripheral
      blood, biopsies of vaccination sites and post-treatment DTH skin tests, and when
      available also in resected abdominal lymph nodes and tumor tissue. RESULTS: Ten
      patients were vaccinated intradermally and intravenously with CEA-peptide pulsed
      mature DCs three times prior to resection of liver metastases. High numbers of
      CEA-specific T cells were detected in post-treatment DTH biopsies in seven out of
      10 patients, which produced high amounts of interferon (IFN)-gamma upon
      stimulation with CEA-loaded target cells. These responses were not found in
      biopsies of first vaccination sites, indicating a de novo T cell induction or at
      least a strong potentiation by the vaccine. In addition, CEA-specific T cells
      were detected in a resected lymph node in one patient, but not in peripheral
      blood or tumor tissue. CONCLUSIONS: Vaccination with CEA-peptide loaded mature
      DCs induced potent CEA-specific T cell responses in advanced colorectal cancer
      patients. In this study, antigen-specific T cell responses were readily detected
      in DTH skin tests, much less in abdominal lymph nodes, and not in peripheral
      blood and tumor tissue.

PMID- 16600980
TI  - A phase I dose-finding clinical pharmacokinetic study of an oral formulation of
      irinotecan (CPT-11) administered for 5 days every 3 weeks in patients with
      advanced solid tumours.
AB  - BACKGROUND: Oral administration of irinotecan (CPT-11) should allow sustained
      exposure to the drug without the inconvenience of intravenous delivery and with
      fewer side-effects. PATIENTS AND METHODS: The present phase I trial of CPT-11,
      administered orally as a powder-filled capsule for 5 consecutive days every 3
      weeks at doses ranging from 30 to 90 mg/m(2)/day, was conducted in 47 patients
      for whom a satisfactory standard treatment option was no longer available (24
      males/23 females; median age 51 years, range 26-85). Tumour types included
      melanoma (11), colorectal (4), urinary tract (3), lung/pleura (4), thyroid (3),
      liver (3), gallbladder (2), cervix/uterus (3), breast (2), pancreas (2),
      carcinoma and other cancer types (10). RESULTS: A total of 171 cycles were
      administered (median 3, range 1-11). Dose limiting toxicities (DLTs) occurred
      during the first cycle in five of 31 patients in the dose-escalation part of the
      study: one patient at the 50 mg/m(2)/day dose level (diarrhoea grade 4); one
      patient at the 80 mg/m(2)/day dose level (prolonged neutropenia grade 4 and
      diarrhoea grade 3); and three patients at the 90 mg/m(2)/day dose level
      (diarrhoea, vomiting and neutropenia). The 80 mg/m(2)/day dose level was
      expanded, as a feasibility study, to include 16 additional patients, five of whom
      had received extensive prior pelvic irradiation. A further three patients in this
      cohort experienced DLTs, two of whom had received extensive prior pelvic
      irradiation. One patient died on study day 15 during the first cycle of oral CPT
      11 following grade 3 diarrhoea, febrile neutropenia and a necrotic enterocolitis.
      Overall the grade 3/4 toxicities in 47 patients were asthenia (19%), anorexia
      (17%), neutropenia (14.9 %), diarrhoea (13%), nausea (12.7%), vomiting (8.5%) and
      thrombocytopenia (8.5%). Partial responses were observed in two melanoma patients
      and disease stabilisation was noted in 17 (36.1%) patients. Pharmacokinetic
      parameters were recorded for 46 patients. CONCLUSIONS: At the maximum tolerated
      dose, defined as 80 mg/m(2)/day for 5 days every 3 weeks, oral CPT-11 was shown
      to be well tolerated and safe with few of the haematological toxicities
      associated with the intravenous formulation.

PMID- 16600981
TI  - Experience of parental cancer in childhood is a risk factor for psychological
      distress during genetic cancer susceptibility testing.
AB  - BACKGROUND: This study explores the effect of age at the time of parental cancer
      diagnosis or death on psychological distress and cancer risk perception in
      individuals undergoing genetic testing for a specific cancer susceptibility.
      PATIENTS AND METHODS: Cancer-related distress, worry and risk perception were
      assessed in 271 applicants for genetic testing of an identified mutation in
      BRCA1/2 (BReast CAncer) or a HNPCC (Hereditary Nonpolyposis Colorectal Cancer)
      related gene before, one week after, and six months after genetic test
      disclosure. The course of distress and risk perception were compared between
      individuals having witnessed parental cancer or loss due to cancer in childhood,
      adolescence, adulthood and having unaffected parents. RESULTS: Individuals with
      parental cancer in childhood (under age 13) reported the highest level of cancer
      related distress, worry and risk perception. Women having their mother affected
      by breast cancer in puberty (aged 10-13 years) perceived higher breast cancer
      risks than women with an affected mother in adulthood or without an affected
      mother. Individuals with an affected parent perceived cancer risks as higher than
      individuals without an affected parent, but were not more distressed.
      CONCLUSIONS: Experience of parental cancer in childhood is a risk factor for
      psychological distress during the genetic testing process.

PMID- 16600982
TI  - Quality of life is predictive of survival in patients with unresectable
      hepatocellular carcinoma.
AB  - BACKGROUND: Patients with unresectable hepatocellular carcinoma (HCC) have a
      dismal prognosis. The objective of this study was to evaluate whether patient
      reported baseline quality of life (QoL) measured by the EORTC QLQ-C30 instrument
      is predictive of survival for these patients. MATERIALS AND METHODS: Two hundred
      and thirty-three patients with unresectable HCC (mainly hepatitis B-associated)
      who were recruited into two separate randomized phase III clinical studies, based
      on palliative chemotherapy and palliative hormonal therapy, respectively, gave
      consent and received pretreatment QoL assessment. EORTC QLQ-C30 scores and
      clinical variables at the time of study entry were analyzed to identify factors
      that influenced survival by applying multivariate analysis. Independent
      prognostic factors for survival were studied by Cox regression analysis. RESULTS:
      Median survival of the 233 patients was 5.5 months (95% CI 4.2-6.5 months).
      Significant independent predictors of shorter survival were advanced Okuda
      staging (P = 0.0030; HR = 2.058), high baseline total bilirubin (P = 0.0008; HR =
      1.013) and worse QoL score in the appetite score domain (P = 0.0028; HR for 10
      point increase = 1.070). Patients who were entered into the chemotherapy trial (P
      = 0.0002; HR = 0.503), those who scored better in the physical functioning domain
      (P = 0.0034; HR for 10 point decrease = 0.911) and the role functioning domain (P
      = 0.0383; HR for 10 point decrease = 0.944) of the QoL questionnaire, were
      associated with longer survival. CONCLUSIONS: In the studied HCC population,
      patient-reported baseline QoL provides additional prognostic information that
      supplements traditional clinical factors, and is a new prognostic marker for
      survival for patients with unresectable HCC.

PMID- 16600983
TI  - Current treatment options and biology of peritoneal mesothelioma: meeting summary
      of the first NIH peritoneal mesothelioma conference.
AB  - Peritoneal mesothelioma is a rare cancer of the peritoneum with about 250 new
      cases diagnosed each year in the United States. It is the second most common site
      for mesothelioma development and accounts for 10-20% of all mesotheliomas
      diagnosed in the United States. A meeting sponsored by the NIH Office of Rare
      Diseases was held in Bethesda, Maryland on September 13 and 14, 2004. The
      objective of this meeting was to review the epidemiology, biology and current
      surgical and medical management of peritoneal mesothelioma. In addition, the
      meeting also discussed clinical and pre-clinical evaluation of novel treatments
      for mesothelioma as well as ongoing laboratory research to better understand this
      disease. This report summarizes the proceedings of the meeting as well as
      directions for future clinical and basic research.

PMID- 16600984
TI  - A phase II monocentric study of oxaliplatin in combination with gemcitabine
      (GEMOX) in patients with advanced/metastatic transitional cell carcinoma (TCC) of
      the urothelial tract.
AB  - BACKGROUND: The aim of the study was to evaluate the activity and the safety of
      the gemcitabine-oxaliplatin (GEMOX) combination as first-line treatment in
      advanced/metastatic transitional cell carcinoma (TCC) of the urothelial tract.
      MATERIALS AND METHODS: Patients with metastatic or unresectable TCC, PS < or =2,
      creatinine < or =1.5 upper limit of normal range (UNL) and measurable disease
      according to RECIST criteria were treated with a combination of gemcitabine (1500
      mg/m(2)) followed by oxaliplatin (85 mg/m(2)) on day 1 and 15 of a 28-day cycle.
      RESULTS: A total of 123 cycles were administered to 30 patients (median 4, range
      1-8). Three complete responses (CR) and 11 partial responses (PR) were observed.
      Overall response rate (ORR) was 47% (95% CI 28% to 66%). Median overall survival
      (OS) was 15 months (95% CI 8-31). Grade 3 and 4 neutropenia were reported in
      three and one patient, respectively; grade 3 anaemia in three patients; grade 3
      and 4 thrombocytopenia in two and one patient, respectively; grade 1, 2 and 3
      peripheral neuropathy in 14, 11 and two patients, respectively; grade 2 and 3
      fatigue in 13 and seven patients respectively. CONCLUSIONS: The GEMOX combination
      is active in advanced/metastatic TCC with minimal toxicity and needs to be
      evaluated in a selected population of unfit patients and compared with other non
      cisplatin-containing regimens.

PMID- 16600986
TI  - Scoring variability of micronuclei in binucleated human lymphocytes in a case
      control study.
AB  - The micronucleus test in binucleated lymphocytes is a sensitive standard assay
      for biomonitoring, mutagenicity testing and to assess radiosensitivity of blood
      donors. The results vary between laboratories and scorers which led to the
      definition of international scoring criteria. We used these criteria in a case
      control study, but nevertheless observed large differences between the seven
      scorers on the level of descriptive analysis. Therefore, we used the repeat
      measurements (267 in 98 blood donors) from this dataset (354 measurements in 185
      blood donors) to analyse scoring variability in the setting of a case-control
      study. The variability was assessed by analysis of variance, which revealed the
      storage time of the blood samples, the blood donors including their disease
      status, and the scorers as sources of variation in the entire dataset. In
      addition, the coefficient of variation (CV) of the measurements was determined
      (overall: CV = 24.3%). After stepwise removal of biological and experimental
      variation by normalizations, the CV dropped to 6.8% on average, which may reflect
      the 'pure counting error'. The scorer-specific CVs were between 5.5 and 9.5%. The
      differences between the scorers suggested by the raw data were neither related to
      the scorer-specific CV nor to their experience. Instead, we observed a general
      decline of the micronuclei frequencies towards the end of the study for all
      scorers. This could not be related to a change in experimental conditions or in
      the defined scoring criteria. An explanation could be an unintended and
      unrecognized change of scoring criteria. Since the change in the results did not
      occur in automated counting we suggest to use either reference slides in longer
      lasting studies or automated counting by image analysis.

PMID- 16600985
TI  - CSF amyloid-beta-peptides in Alzheimer's disease, dementia with Lewy bodies and
      Parkinson's disease dementia.
AB  - As the differential diagnosis of dementias based on established clinical criteria
      is often difficult, biomarkers for applicable diagnostic testing are currently
      under intensive investigation. Amyloid plaques deposited in the brain of patients
      suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and
      Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated
      forms of amyloid-beta (Abeta) peptides, such as Abeta1-42. Absolute Abeta1-42
      levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's
      disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor.
      A recently established quantitative urea-based Abeta-sodium-dodecylsulphate
      polyacrylamide-gel-electrophoresis with Western immunoblot (Abeta-SDS
      PAGE/immunoblot) revealed a highly conserved Abeta peptide pattern of the carboxy
      terminally truncated Abeta peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42
      in human CSF. We used the Abeta-SDS-PAGE/immunoblot to investigate the CSF of 23
      patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented
      disease controls (NDC) for disease-specific alterations of the Abeta peptide
      patterns in its absolute and relative quantities. The diagnostic groups were
      matched for age and severity of dementia. The present study is the first attempt
      to evaluate the meaning of Abeta peptide patterns in CSF for differential
      diagnosis of the three neurodegenerative diseases--Alzheimer's disease, DLB and
      PDD. The Abeta peptide patterns displayed disease-specific variations and the
      ratio of the differentially altered Abeta1-42 to the Abeta1-37 levels
      subsequently discriminated all diagnostic groups from each other at a highly
      significant level, except DLB from PDD. Additionally, a novel peptide with Abeta
      like immunoreactivity was observed constantly in the CSF of all 88 investigated
      patients. The pronounced percentage increase of this peptide in DLB allowed a
      highly significant discrimination from PDD. Using a cut-off point of 0.954%, this
      marker yielded a diagnostic sensitivity and specificity of 81 and 71%,
      respectively. From several lines of indication, we consider this peptide to
      represent an oxidized alpha-helical form of Abeta1-40 (Abeta1-40*). The increased
      abundance of Abeta1-40* probably reflects a disease-specific alteration of the
      Abeta1-40 metabolism in DLB. We conclude that Abeta peptide patterns reflect
      disease-specific pathophysiological pathways of different dementia syndromes as
      distinct neurochemical phenotypes. Although Abeta peptide patterns failed to
      fulfil the requirements for a sole biomarker, their combined evaluation with
      other biomarkers is promising in neurochemical dementia diagnosis. It is
      noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite
      their similar neuropathological appearance. Their distinct molecular phenotypes
      support the view of different pathophysiological pathways for each of these
      neurodegenerative diseases.

PMID- 16600987
TI  - E-cadherin missense mutations, associated with hereditary diffuse gastric cancer
      (HDGC) syndrome, display distinct invasive behaviors and genetic interactions
      with the Wnt and Notch pathways in Drosophila epithelia.
AB  - Germline mutations in the human E-cadherin (hEcad) gene, CDH1, are initiating
      events in cases of human hereditary diffuse gastric cancer (HDGC) indicating that
      hEcad is a tumor suppressor. Among the hEcad mutations identified so far, some
      are missense, but the pathological relevance of these missense mutants is still
      unclear. In vitro assays show that missense mutations result in full-length hEcad
      molecules that retain some distinct biological activity, but in vivo functional
      studies in animal models are still lacking. Here we verify the potential of a
      Drosophila model to in vivo characterize the functional consequences of HDGC
      associated germline missense mutations and to identify signaling pathways
      affected by these mutations. To this end, we have generated transgenic fly
      strains expressing the wild-type hEcad gene or its missense mutations. Similar to
      the fly Ecad, expression of wild-type hEcad and missense forms in fly epithelia
      resulted in their localization to the subapical region. In addition, we verify a
      genotype-phenotype correlation associated to the specific domain affected by the
      mutations, because cells expressing normal or missense mutant hEcad display
      different migratory and invasive behaviors in fly epithelia. We show that some of
      these effects might be mediated through hEcad interacting with the endogenous fly
      ss-catenin, Armadillo, thus interfering with the Wnt signaling pathway.
      Therefore, the use of this simple in vivo system will contribute to characterize
      the effects that missense hEcad have on cell behavior in a tissue environment,
      and might help to understand their significance in gastric cancer onset.

PMID- 16600988
TI  - Early development of aberrant synaptic plasticity in a mouse model of
      Huntington's disease.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by
      progressive motor, psychiatric and cognitive decline. Marked neuronal loss occurs
      in the cortex and striatum. HD is inherited in an autosomal dominant fashion and
      caused by a trinucleotide repeat expansion (CAG) in the gene encoding the protein
      huntingtin. Predictive genetic testing has revealed early cognitive deficits in
      asymptomatic gene carriers at a time when there is little evidence for cell
      death, suggesting that impaired cognition results from a cellular or synaptic
      deficit, such as aberrant synaptic plasticity. Altered hippocampal long-term
      potentiation has been reported in mouse models of HD; however, the relationship
      between synaptic dysfunction and phenotype progression has not previously been
      characterized. We examined the age-dependency of aberrant hippocampal synaptic
      plasticity in the R6/1 mouse model of HD. Long-term depression (LTD) is a
      developmentally regulated form of plasticity, which normally declines by early
      adulthood. Young R6/1 mice follow the same pattern of LTD expression as controls,
      in that they express LTD in the first weeks of life, and then lose the ability
      with age. Unlike controls, R6/1 synapses later regain the ability to support LTD.
      This is associated with nuclear localization of mutant huntingtin, but occurs
      months prior to the formation of nuclear aggregates. We present the first
      detailed description of a progressive derailment of a functional neural correlate
      of cognitive processing in HD.

PMID- 16600989
TI  - Disease mechanisms in late-onset retinal macular degeneration associated with
      mutation in C1QTNF5.
AB  - Late-onset retinal macular degeneration (L-ORMD) is an autosomal dominant
      condition resembling age-related macular degeneration (AMD) in which a key
      pathological feature is a thick extracellular sub-retinal pigment epithelial
      (RPE) deposit. L-ORMD is caused by mutation in the C1QTNF5 (CTRP5) short-chain
      collagen gene, but the disease mechanism is unknown. Here, we first show that
      wild-type C1QTNF5 is secreted, whereas mutant C1QTNF5 is misfolded and retained
      within the endoplasmic reticulum (ER). Secondly, the ER retained mutant protein
      has a shorter half-life than wild-type C1QTNF5 and is preferentially degraded by
      proteasomes. Thirdly, C1QTNF5 is shown to interact with the membrane-type
      frizzled related protein (MFRP), on the basis of yeast two-hybrid, protein pull
      down and co-immunoprecipitation assays and RPE co-localization. These data
      suggest that L-ORMD is due to insufficient levels of secreted C1QTNF5,
      compromised RPE cell function resulting from ER retention of the mutant protein
      or both mechanisms.

PMID- 16600990
TI  - Neuropeptide S and G protein-coupled receptor 154 modulate macrophage immune
      responses.
AB  - G protein-coupled receptor 154 (GPR154) is a recently discovered asthma
      susceptibility gene upregulated in the airways of asthma patients. We previously
      observed increased pulmonary mRNA expression of the murine ortholog Gpr154 in a
      mouse model of ovalbumin (OVA)-induced inflammation. However, the expression
      profile of GPR154 in leukocytes and the cellular functions of the receptor and
      its endogenous agonist neuropeptide S (NPS) have remained unidentified. Here, we
      characterized the mRNA expression of NPS and GPR154 by using real-time RT-PCR in
      fractionated human blood cells and in peripheral blood mononuclear cells (PBMCs)
      with monocyte or T cell activation. The expression of GPR154 in leukocytes was
      further confirmed by immunoblotting experiments and immunohistochemical staining
      of human sputum samples. Additionally, we characterized the expression of GPR154
      in the lung tissue samples and in the bronchoalveolar lavage (BAL) fluid of OVA
      sensitized and challenged BALB/c mice. In human blood and sputum cells,
      monocyte/macrophages and eosinophils were identified as GPR154-positive cells. In
      PBMCs, monocyte activation with LPS but not T cell activation with anti-CD3/CD28
      antibodies resulted in increased NPS and GPR154 expression. In the lung tissue
      samples and in the BAL fluid of OVA-challenged mice, GPR154 expression was
      upregulated in alveolar macrophages in comparison to controls. In the mouse
      macrophage RAW 264.7 cell line, NPS-stimulated Galphas- and Galphaq-dependent
      phagocytosis of Escherichia coli. The results show that GPR154 is upregulated in
      macrophages after antigen challenge and that NPS is capable of inducing
      phagocytosis of unopsonized bacteria.

PMID- 16600991
TI  - The chromosome 6p22 haplotype associated with dyslexia reduces the expression of
      KIAA0319, a novel gene involved in neuronal migration.
AB  - Dyslexia is one of the most prevalent childhood cognitive disorders, affecting
      approximately 5% of school-age children. We have recently identified a risk
      haplotype associated with dyslexia on chromosome 6p22.2 which spans the TTRAP
      gene and portions of THEM2 and KIAA0319. Here we show that in the presence of the
      risk haplotype, the expression of the KIAA0319 gene is reduced but the expression
      of the other two genes remains unaffected. Using in situ hybridization, we detect
      a very distinct expression pattern of the KIAA0319 gene in the developing
      cerebral neocortex of mouse and human fetuses. Moreover, interference with rat
      Kiaa0319 expression in utero leads to impaired neuronal migration in the
      developing cerebral neocortex. These data suggest a direct link between a
      specific genetic background and a biological mechanism leading to the development
      of dyslexia: the risk haplotype on chromosome 6p22.2 down-regulates the KIAA0319
      gene which is required for neuronal migration during the formation of the
      cerebral neocortex.

PMID- 16600992
TI  - Tissue-specific roles of Tbx1 in the development of the outer, middle and inner
      ear, defective in 22q11DS patients.
AB  - Most 22q11.2 deletion syndrome (22q11DS) patients have middle and outer ear
      anomalies, whereas some have inner ear malformations. Tbx1, a gene hemizygously
      deleted in 22q11DS patients and required for ear development, is expressed in
      multiple tissues during embryogenesis. To determine the role of Tbx1 in the first
      pharyngeal pouch (PPI) in forming outer and middle ears, we tissue-specifically
      inactivated the gene using Foxg1-Cre. In the conditional mutants, PPI failed to
      outgrow, preventing the middle ear bone condensations from forming. Tbx1 was also
      inactivated in the otic vesicle (OV), resulting in the failure of inner ear
      sensory organ formation, and in duplication of the cochleovestibular ganglion
      (CVG). Consistent with the anatomical defects, the sensory genes, Otx1 and Bmp4
      were downregulated, whereas the CVG genes, Fgf3 and NeuroD, were upregulated. To
      delineate Tbx1 cell-autonomous roles, a more selective ablation, exclusively in
      the OV, was performed using Pax2-Cre. In contrast to the Foxg1-Cre mutants, Pax2
      Cre conditional mutant mice survived to adulthood and had normal outer and middle
      ears but had the same inner ear defects as the Tbx1 null mice, with the same gene
      expression changes. These results demonstrate that Tbx1 has non-cell autonomous
      roles in PPI in the formation of outer and middle ears and cell-autonomous roles
      in the OV. Periotic mesenchymal markers, Prx2 and Brn4 were normal in both
      conditional mutants, whereas they were diminished in Tbx1-/- embryos. Thus, Tbx1
      in the surrounding mesenchyme in both sets of conditional mutants cannot suppress
      the defects in the OV that occur in the null mutants.

PMID- 16600993
TI  - Context-specific functional effects of IFNGR1 promoter polymorphism.
AB  - We report evidence of a polymorphism in the promoter region of IFNGR1 (encoding
      interferon-gamma receptor 1) that has opposite functional effects in different
      cellular contexts. It is a deletion/insertion polymorphism that is found in
      Africans but not Europeans or Asians, and has been associated with resistance to
      severe malaria. We find that the IFNGR1-470del allele acts to suppress binding of
      nuclear proteins to the IFNGR1 promoter region in a manner that is specific for
      cell type. In B-lymphocytes, the IFNGR1-470del allele suppresses the binding of a
      approximately 35 kDa nuclear protein and acts to increase reporter gene
      expression. In epithelial cells, the same allele acts to decrease gene expression
      and suppresses the binding of approximately 90 kDa STAT-1 and STAT-2 proteins. In
      T-lymphocytes, this allele causes only subtle differences in nuclear protein
      binding and has no significant effect on gene expression. These findings suggest
      a mechanism by which a single genetic variant may cause a broad range of
      phenotypic consequences.

PMID- 16600994
TI  - Molecular pathways that influence human tau-induced pathology in Caenorhabditis
      elegans.
AB  - Mutations in the gene encoding tau cause frontotemporal dementia with
      parkinsonism--chromosome 17 type (FTDP-17). In FTDP-17, Alzheimer's disease, and
      other tauopathies, aggregated hyper-phosphorylated tau forms the neurofibrillary
      tangles characteristic of these disorders. We previously reported a
      Caenorhabditis elegans model for tauopathies using human normal and FTDP-17
      mutant tau as transgenes. Neuronal transgene expression caused insoluble
      phosphorylated tau accumulation, neurodegeneration and uncoordinated (Unc)
      movement. Here we describe a genome-wide RNA-mediated interference (RNAi) screen
      for genes that modify the tau-induced Unc phenotype. We tested RNAi sequences for
      16,757 genes and found 75 that enhanced the transgene-induced Unc phenotype.
      Forty-six of these genes have sequence similarity to known human genes and fall
      into a number of broad classes including kinases, chaperones, proteases and
      phosphatases. The remaining 29 modifiers have sequence similarity only with other
      nematode genes. To determine if the enhancers are specific for the tau-induced
      Unc behavior, we exposed several non-tau Unc mutants to tau RNAi enhancer clones.
      Fifteen enhancers modified phenotypes in multiple Unc mutants, whereas 60
      modified only the Unc phenotype in the tau transgenic lines. We also introduced
      the tau transgene into the background of genetic loss-of-function mutations for a
      subset of the enhancer genes. Tau transgenic animals homozygous for loss of these
      enhancer genes exhibited increased impaired motility relative to the tau
      transgene line alone. This work uncovers novel candidate genes that prevent tau
      toxicity, as well as genes previously implicated in tau-mediated
      neurodegeneration.

PMID- 16600995
TI  - A quest for human and mouse embryonic stem cell-specific proteins.
AB  - Embryonic stem cells (ESCs) are of immense interest as they can proliferate
      indefinitely in vitro and give rise to any adult cell type, serving as a
      potentially unlimited source for tissue replacement in regenerative medicine.
      Extensive analyses of numerous human and mouse ESC lines have shown generic
      similarities and differences at both the transcriptional and functional level.
      However, comprehensive proteome analyses are missing or are restricted to mouse
      ESCs. Here we have used an extensive proteomic approach to search for ESC
      specific proteins by analyzing the differential protein expression profiles of
      human and mouse ESCs and their differentiated derivatives. The data sets comprise
      1,775 non-redundant proteins identified in human ESCs, 1,532 in differentiated
      human ESCs, 1,871 in mouse ESCs, and 1,552 in differentiated mouse ESCs with a
      false positive rate of <0.2%. Comparison of the data sets distinguished 191
      proteins exclusively identified in both human and mouse ESCs but not in their
      differentiated derivatives. Besides well known ESC benchmarks, this subset
      included many uncharacterized proteins, some of which may be novel ESC-specific
      markers. To complement the mass spectrometric approach, differential expression
      of a selection of these proteins was confirmed by Western blotting,
      immunofluorescence confocal microscopy, and fluorescence-activated cell sorting.
      Additionally two other independently isolated and cultured human ESC lines as
      well as their differentiated derivatives were monitored for differential
      expression of selected proteins. Some of these proteins were identified
      exclusively in ESCs of all three human lines and may thus serve as generic ESC
      markers. Our wide scale proteomic approach enabled us to screen thousands of
      proteins rapidly and select putative ESC-associated proteins for further
      analysis. Validation by three independent conventional protein analysis
      techniques shows that our methodology is robust, provides an excellent tool to
      characterize ESCs at the protein level, and may disclose novel ESC-specific
      benchmarks.

PMID- 16600996
TI  - Protein synthesis a low priority for exercising muscle.

PMID- 16600997
TI  - Signalling during hypoxia in human T lymphocytes--critical role of the src
      protein tyrosine kinase p56Lck in the O2 sensitivity of Kv1.3 channels.
AB  - T lymphocytes encounter hypoxia when they migrate to pathological sites such as
      tumours and wounds. The inability of T cells to provide an efficient defence at
      these sites can in part be explained by the hypoxic environment. Kv 1.3 channels,
      important components of the T cell activation process are inhibited by hypoxia
      and their inhibition accounts for a hypoxia-induced decrease in T cell
      proliferation. Although Kv 1.3 channels play a key role in T cell O(2) sensing,
      the signalling mechanisms mediating their response to hypoxia are still not
      understood. In this study, we show that the src-protein tyrosine kinase p56Lck
      (Lck) is required for Kv 1.3 channel response to hypoxia. Pre-exposure to the src
      inhibitor PP2 abolished the hypoxia-induced inhibition of Kv 1.3 channels in
      primary human T lymphocytes. Moreover, Kv 1.3 channel sensitivity to hypoxia was
      lost in Lck-deficient Jurkat T cells. Further studies with recombinant Kv 1.3
      channels showed that Kv 1.3 channels lack intrinsic O(2) sensitivity, but
      delivery of Lck into the cells and transfection of a constitutively active Lck
      (Y505FLck) restored their sensitivity to hypoxia. Although Lck is necessary for
      the Kv 1.3 channel response to hypoxia, it does not directly inhibit Kv 1.3
      channels. Indeed, under normal oxygen tension, delivery of active Lck into L929
      cells and overexpression of Y505FLck did not decrease recombinant Kv 1.3
      currents. On the contrary, activation of endogenous src kinases increased wild
      type Kv 1.3 currents in T lymphocytes. Our findings indicate that Lck is required
      for the acute response to hypoxia of human T lymphocytes as it is necessary to
      confer O(2) sensitivity on Kv 1.3 channels.

PMID- 16600999
TI  - CpG + CpNpG analysis of protein-coding sequences from tomato.
AB  - We develop codon-based models for simultaneously inferring the mutational effects
      of CpG and CpNpG methylation in coding regions. In a data set of 369 tomato
      genes, we show that there is very little effect of CpNpG methylation but a strong
      effect of CpG methylation affecting almost all genes. We further show that the
      CpNpG and CpG effects are largely uncorrelated. Our results suggest different
      roles of CpG and CpNpG methylation, with CpNpG methylation possibly playing a
      specialized role in defense against transposons and RNA viruses.

PMID- 16600998
TI  - Higher skeletal muscle alpha2AMPK activation and lower energy charge and fat
      oxidation in men than in women during submaximal exercise.
AB  - 5'AMP-activated protein kinase (AMPK) is an energy sensor activated by perturbed
      cellular energy status such as during muscle contraction. Activated AMPK is
      thought to regulate several key metabolic pathways. We used sex comparison to
      investigate whether AMPK signalling in skeletal muscle regulates fat oxidation
      during exercise. Moderately trained women and men completed 90 min bicycle
      exercise at 60% VO2peak. Both AMPK Thr172 phosphorylation and alpha2AMPK activity
      were increased by exercise in men (approximately 200%, P < 0.001) but not
      significantly in women. The sex difference in muscle AMPK activation with
      exercise was accompanied by an increase in muscle free AMP (approximately 164%, P
      < 0.01), free AMP/ATP ratio (159%, P < 0.05), and creatine (approximately 42%, P
      < 0.001) in men but not in women (NS), suggesting that lack of AMPK activation in
      women was due to better maintenance of muscle cellular energy balance compared
      with men. During exercise, fat oxidation per kg lean body mass was higher in
      women than in men (P < 0.05). Regression analysis revealed that a higher
      proportion of type 1 muscle fibres (approximately 23%, P < 0.01) and a higher
      capillarization (approximately 23%, P < 0.05) in women than in men could partly
      explain the sex difference in alpha2AMPK activity (r = -0.54, P < 0.05) and fat
      oxidation (r = 0.64, P < 0.05) during exercise. On the other hand, fat oxidation
      appeared not to be regulated via AMPK. In conclusion, during prolonged submaximal
      exercise at 60% VO2peak, higher fat oxidation in women cannot be explained by
      higher AMPK signalling but is accompanied by improved muscle cellular energy
      balance in women probably due to sex specific muscle morphology.

PMID- 16601000
TI  - Evolution of paralogous genes: Reconstruction of genome rearrangements through
      comparison of multiple genomes within Staphylococcus aureus.
AB  - Analysis of evolution of paralogous genes in a genome is central to our
      understanding of genome evolution. Comparison of closely related bacterial
      genomes, which has provided clues as to how genome sequences evolve under natural
      conditions, would help in such an analysis. With species Staphylococcus aureus,
      whole-genome sequences have been decoded for seven strains. We compared their DNA
      sequences to detect large genome polymorphisms and to deduce mechanisms of genome
      rearrangements that have formed each of them. We first compared strains N315 and
      Mu50, which make one of the most closely related strain pairs, at the single
      nucleotide resolution to catalogue all the middle-sized (more than 10 bp) to
      large genome polymorphisms such as indels and substitutions. These polymorphisms
      include two paralogous gene sets, one in a tandem paralogue gene cluster for
      toxins in a genomic island and the other in a ribosomal RNA operon. We also
      focused on two other tandem paralogue gene clusters and type I restriction
      modification (RM) genes on the genomic islands. Then we reconstructed
      rearrangement events responsible for these polymorphisms, in the paralogous genes
      and the others, with reference to the other five genomes. For the tandem
      paralogue gene clusters, we were able to infer sequences for homologous
      recombination generating the change in the repeat number. These sequences were
      conserved among the repeated paralogous units likely because of their functional
      importance. The sequence specificity (S) subunit of type I RM systems showed
      recombination, likely at the homology of a conserved region, between the two
      variable regions for sequence specificity. We also noticed novel alleles in the
      ribosomal RNA operons and suggested a role for illegitimate recombination in
      their formation. These results revealed importance of recombination involving
      long conserved sequence in the evolution of paralogous genes in the genome.

PMID- 16601001
TI  - GRAST: a new way of genome reduction analysis using comparative genomics.
AB  - MOTIVATION: Establishment of intra-cellular life involved a profound re
      configuration of the genetic characteristics of bacteria, including genome
      reduction and rearrangements. Understanding the mechanisms underlying these
      phenomena will shed light on the genome rearrangements essential for the
      development of an intra-cellular lifestyle. Comparison of genomes with
      differences in their sizes poses statistical as well as computational problems.
      Little efforts have been made to develop flexible computational tools with which
      to analyse genome reduction and rearrangements. RESULTS: Investigation of genome
      reduction and rearrangements in endosymbionts using a novel computational tool
      (GRAST) identified gathering of genes with similar functions. Conserved clusters
      of functionally related genes (CGSCs) were detected. Heterogeneous gene and gene
      cluster non-functionalization/loss are identified between genome regions,
      functional gene categories and during evolution. Results show that gene non
      functionalisation has accelerated during the last 50 MY of Buchnera's evolution
      while CGSCs have been static.

PMID- 16601002
TI  - Intrinsically disordered C-terminal segments of voltage-activated potassium
      channels: a possible fishing rod-like mechanism for channel binding to scaffold
      proteins.
AB  - Membrane-embedded voltage-activated potassium channels (Kv) bind intracellular
      scaffold proteins, such as the Post Synaptic Density 95 (PSD-95) protein, using a
      conserved PDZ-binding motif located at the channels' C-terminal tip. This
      interaction underlies Kv-channel clustering, and is important for the proper
      assembly and functioning of the synapse. Here we demonstrate that the C-terminal
      segments of Kv channels adjacent to the PDZ-binding motif are intrinsically
      disordered. Phylogenetic analysis of the Kv channel family reveals a cluster of
      channel sequences belonging to three out of the four main channel families, for
      which an association is demonstrated between the presence of the consensus
      terminal PDZ-binding motif and the intrinsically disordered nature of the
      immediately adjacent C-terminal segment. Our observations, combined with a
      structural analogy to the N-terminal intra-molecular ball-and-chain mechanism for
      Kv channel inactivation, suggest that the C-terminal disordered segments of these
      channel families encode an inter-molecular fishing rod-like mechanism for K(+)
      channel binding to scaffold proteins.

PMID- 16601003
TI  - SNAP: Combine and Map modules for multilocus population genetic analysis.
AB  - We have added two software tools to our Suite of Nucleotide Analysis Programs
      (SNAP) for working with DNA sequences sampled from populations. SNAP Map
      collapses DNA sequence data into unique haplotypes, extracts variable sites and
      manipulates output into multiple formats for input into existing software
      packages for evolutionary analyses. Map collapses DNA sequence data into unique
      haplotypes, extracts variable sites and manipulates output into multiple formats
      for input into existing software packages for evolutionary analyses. Map includes
      novel features such as recoding insertions or deletions, including or excluding
      variable sites that violate an infinite-sites model and the option of collapsing
      sequences with corresponding phenotypic information, important in testing for
      significant haplotype-phenotype associations. SNAP Combine merges multiple DNA
      sequence alignments into a single multiple alignment file. The resulting file can
      be the union or intersection of the input files. SNAP Combine currently reads
      from and writes to several sequence alignment file formats including both
      sequential and interleaved formats. Combine also keeps track of the start and end
      positions of each separate alignment file allowing the user to exclude variable
      sites or taxa, important in creating input files for multilocus analyses.

PMID- 16601004
TI  - Gene fusion/fission is a major contributor to evolution of multi-domain bacterial
      proteins.
AB  - Most proteins comprise one or several domains. New domain architectures can be
      created by combining previously existing domains. The elementary events that
      create new domain architectures may be categorized into three classes, namely
      domain(s) insertion or deletion (indel), exchange and repetition. Using
      'DomainTeam', a tool dedicated to the search for microsyntenies of domains, we
      quantified the relative contribution of these events. This tool allowed us to
      collect homologous bacterial genes encoding proteins that have obviously evolved
      by modular assembly of domains. We show that indels are the most frequent
      elementary events and that they occur in most cases at either the N- or C
      terminus of the proteins. As revealed by the genomic neighbourhood/context of the
      corresponding genes, we show that a substantial number of these terminal indels
      are the consequence of gene fusions/fissions. We provide evidence showing that
      the contribution of gene fusion/fission to the evolution of multi-domain
      bacterial proteins is lower-bounded by 27% and upper-bounded by 64%. We conclude
      that gene fusion/fission is a major contributor to the evolution of multi-domain
      bacterial proteins.

PMID- 16601005
TI  - Analysing the ability to retain sidechain hydrogen-bonds in mutant proteins.
AB  - MOTIVATION: Hydrogen bonds are one of the most important inter-atomic
      interactions in biology. Previous experimental, theoretical and bioinformatics
      analyses have shown that the hydrogen bonding potential of amino acids is
      generally satisfied and that buried unsatisfied hydrogen-bond-capable residues
      are destabilizing. When studying mutant proteins, or introducing mutations to
      residues involved in hydrogen bonding, one needs to know whether a hydrogen bond
      can be maintained. Our aim, therefore, was to develop a rapid method to evaluate
      whether a sidechain can form a hydrogen-bond. RESULTS: A novel knowledge-based
      approach was developed in which the conformations accessible to the residues
      involved are taken into account. Residues involved in hydrogen bonds in a set of
      high resolution crystal structures were analyzed and this analysis is then
      applied to a given protein. The program was applied to assess mutations in the
      tumour-suppressor protein, p53. This raised the number of distinct mutations
      identified as disrupting sidechain-sidechain hydrogen bonding from 181 in our
      previous analysis to 202 in this analysis.

PMID- 16601006
TI  - Evaluation of in vivo conception after testicular stem cell transplantation in a
      mouse model shows altered post-implantation development.
AB  - BACKGROUND: Apart from research applications, testicular stem cell
      transplantation (TSCT) may one day also have valuable clinical applications.
      Therefore, it is important to investigate whether this technique is a safe method
      to have progeny. This controlled study aims at evaluating the fetuses and the
      live born offspring obtained after TSCT in male mice. METHODS: Male mice were
      mated with wild-type (WT) females after TSCT to produce offspring. First, fetuses
      were evaluated on the 17th gestational day. The length, weight and morphological
      age were compared to those of control mouse fetuses. The live born offspring were
      then investigated for their reproductive potential over three generations.
      RESULTS: The litter sizes after TSCT were decreased compared to controls. Fetuses
      showed developmental retardation of a quarter of a day, but no major external
      abnormalities were observed. The live born pups were able to produce normal
      litter sizes, at least until the third generation. CONCLUSIONS: Transplanted
      animals are able to reproduce naturally. Although litter sizes are lower and
      development is retarded, no major morphological or procreative abnormalities were
      observed.

PMID- 16601007
TI  - Subfertility guidelines in Europe: the quantity and quality of intrauterine
      insemination guidelines.
AB  - BACKGROUND: International collaboration could facilitate systematic development
      of guidelines to regulate and improve clinical practice. To promote European
      collaboration in guideline development in reproductive medicine, insight into
      existing subfertility guidelines in Europe is essential. The study aim was to
      explore the number and quality of clinical practice guidelines on homologous
      intrauterine insemination (IUI) in Europe. METHODS: To identify IUI guidelines in
      Europe, electronic databases and Internet were systematically searched and key
      experts on assisted reproduction in 25 European countries were questioned. The
      quality of IUI guidelines was systematically assessed with the internationally
      validated Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument.
      Qualitative methods were used to appraise IUI guideline recommendations and
      references. RESULTS: National guidelines on IUI are available in four of 25
      European countries. The quality of IUI guidelines in Europe is moderate to high,
      but the recommendations and references differ considerably. CONCLUSIONS: The
      number of IUI guidelines in Europe is surprisingly small, and differences in
      their recommendations and references are considerable. To overcome these
      deficiencies in clinical guidance on IUI care in Europe, a central body with
      expertise in up-to-date guideline development methodology and sufficient
      resources could be established in Europe for central selection and international
      exchange of evidence to support guideline recommendations.

PMID- 16601008
TI  - Comparison of follicular fluid IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A
      concentrations and their ratios between GnRH agonist and GnRH antagonist
      protocols for controlled ovarian stimulation in IVF-embryo transfer patients.
AB  - BACKGROUND: Insulin-like growth factors (IGF) and their binding proteins (IGFBP)
      play a major role in the autocrine and paracrine regulation of folliculogenesis.
      This is the first study that has compared follicular fluid (FF) IGF-I, IGF-II,
      IGFBP-3, IGFBP-4 and pregnancy-associated plasma protein (PAPP)-A concentrations,
      and their ratios, to investigate whether there was any difference in the
      intrafollicular microenvironment between the GnRH agonist (GnRHa) and antagonist
      (GnRHant) protocols for controlled ovarian stimulation (COS). METHODS: A total of
      68 IVF cycles were included in this study; two groups were studied: GnRHa long
      protocol group (n = 36) and the flexible GnRHant multiple-dose protocol group (n
      = 32). FF was obtained from dominant follicles during oocyte retrieval and stored
      at -70 degrees C until assayed. IGF-I, IGF-II and IGFBP-3 concentrations were
      measured by radioimmunoassay and IGFBP-4 and PAPP-A by enzyme-linked
      immunosorbent assay. RESULTS: The duration of COS was significantly longer, and
      total dose of gonadotrophins used, serum estradiol (E(2)) levels on hCG day and
      the number of oocytes retrieved were significantly higher in the GnRHa long
      protocol group. The concentrations of FF IGF-II and IGFBP-4 were significantly
      higher, and the ratio of IGF-I/IGFBP-4 was significantly lower in the GnRHa long
      protocol group. Serum E(2) levels per mature follicle were not different between
      the two groups. CONCLUSIONS: Our data may indicate a difference of
      intrafollicular microenvironment between cycles using GnRHa long protocols and
      those using GnRHant protocols. However, the difference in microenvironment does
      not appear to result in a difference in clinical outcome.

PMID- 16601009
TI  - Sperm integrity pre- and post-chemotherapy in men with testicular germ cell
      cancer.
AB  - BACKGROUND: While (partial) recovery of spermatogenesis, observed by means of
      standard semen analysis, has been seen in testicular cancer patients after
      chemotherapy with cisplatin, sperm genomic integrity and its implication for the
      patient's fertility are poorly understood. METHODS: Semen and serum from 22
      patients treated for testicular cancer were analysed pre- and post-chemotherapy.
      Besides routine semen analysis, sperm samples were evaluated by computerized
      karyometric image analysis (CKIA), chromomycin-A3 assay (CMA3, chromatin
      condensation) and TdT-mediated dUTP nick-end labelling assay (TUNEL, DNA damage).
      Serum FSH, LH and testosterone concentrations were measured. RESULTS: Ejaculate
      volume decreased post-chemotherapy (P<0.05). External sperm characteristics (CKIA
      morphometry) and sperm counts did not deteriorate after chemotherapy. An
      improvement in DNA condensation was assessed after chemotherapy (37 versus 50%
      and 47.5 versus 63.7% for CMA3 and CKIA respectively; both P<0.005); yet a high
      percentage of TUNEL-positive sperm was found in the samples (21 versus 25% for
      pre- and post-chemotherapy samples respectively). These values were significantly
      higher than those of a convenience sample of normozoospermic males attending pre
      IVF screening. Serum FSH and LH (IU/l) increased after chemotherapy compared with
      pretreatment levels (8.1 versus 16.7 and 4.5 vs 6.8; both P<0.05, respectively).
      CONCLUSIONS: Despite the improvement in sperm chromatin packaging after
      chemotherapy, an abnormally high percentage of DNA-damaged sperm was found in
      these samples. As sperm quality does not reach normal levels after treatment, it
      remains difficult to outline the best strategy and guidance concerning fertility
      potential of testicular cancer patients.

PMID- 16601010
TI  - Predicting the outcome of pregnancies of unknown location: Bayesian networks with
      expert prior information compared to logistic regression.
AB  - BACKGROUND: As women present at earlier gestations to early pregnancy units
      (EPUs), the number of women diagnosed with a pregnancy of unknown location (PUL)
      increases. Some of these women will have an ectopic pregnancy (EP), and it is
      this group in the PUL population that poses the greatest concern. The aim of this
      study was to develop Bayesian networks to predict EPs in the PUL population.
      METHODS: Data were gathered in a single EPU from all women with a PUL. This data
      set was divided into a model-building (599 women with 44 EPs) and a validation
      (257 women with 22 EPs) data set and consisted of the following variables:
      vaginal bleeding, fluid in the pouch of Douglas, midline echo, lower abdominal
      pain, age, endometrial thickness, gestation days, the ratio of HCG at 48 and 0 h,
      progesterone levels (0 and 48 h) and the clinical outcome of the PUL. We
      developed Bayesian networks with expert information using this data set to
      predict EPs. RESULTS: The best Bayesian network used the gestational age, HCG
      ratio and the progesterone level at 48 h and had an area under the receiver
      operator characteristic curve (AUC) of 0.88 for predicting EPs when tested
      prospectively. CONCLUSIONS: Discrete-valued Bayesian networks are more complex to
      build than, for example, logistic regression. Nevertheless, we have demonstrated
      that such models can be used to predict EPs in a PUL population. Prospective
      interventional multicentre studies are needed to validate the use of such models
      in clinical practice.

PMID- 16601012
TI  - Causes of death and renal tubular dysfunction in residents exposed to cadmium in
      the environment.
AB  - OBJECTIVES: To clarify the causes of death of residents with renal tubular
      dysfunction induced by cadmium (Cd) in the environment. METHODS: A 15 year follow
      up study was performed with the inhabitants living in the Cd polluted Kakehashi
      River basin in Japan. Standardised mortality ratios (SMRs) for causes of death,
      classified by ICD-9, were computed using the person-years method to investigate
      the excess mortality of subjects with urinary beta2-MG (microglobulin) > or =1000
      microg/gCr. Mortality risk analysis was performed using Cox's proportional model
      to compare mortality between subjects with urinary beta2-MG > or =1000 and <1000
      microg/gCr, and to investigate the relationship between the degree of urinary
      beta2-MG and mortality. RESULTS: Excess mortality due to heart failure and
      cerebral infarction in both sexes, and nephritis and nephrosis in men, was
      observed among subjects with urinary beta2-MG > or =1000 microg/gCr. Significant
      increases in mortality risk for cerebral infarction in men and for malignant
      neoplasms in women with urinary beta2-MG > or =1000 microg/gCr were observed
      during the first five year observation period. For nephritis and nephrosis, the
      mortality risks for men and women with urinary beta2-MG > or =1000 microg/gCr
      significantly increased over the 15 year observation period. The mortality risks
      for heart failure and cerebral infarction increased in proportion to the
      increased urinary beta2-MG in both sexes. Increased mortality risks for nephritis
      and nephrosis were identified in the subjects with urinary beta2-MG > or =10000
      microg/gCr in both sexes. CONCLUSION: Renal tubular dysfunction induced by Cd
      affected the causes of death, and mortality for heart failure, cerebral
      infarction, and nephritis and nephrosis was increased among inhabitants living in
      a Cd polluted area in Japan. In women, cancer mortality may have been increased
      while Cd pollution was ongoing.

PMID- 16601013
TI  - Occupational exposure to eight organic dusts and respiratory cancer among Finns.
AB  - BACKGROUND: There is inconclusive evidence concerning cancer risks of organic
      dusts. AIM: The carcinogenic exposures are mainly inhalatory and the authors
      therefore studied associations between occupational exposure to eight different
      organic dusts and respiratory cancers in Finland. METHODS: The authors followed
      up a cohort of all economically active Finns born between 1906 and 1945 for 30
      million person-years during 1971-95. Incident cases of nasal, laryngeal, and lung
      cancer and mesotheliomas were identified through a record linkage with the
      Finnish Cancer Registry. Occupations from the population census in 1970 were
      converted to exposures to eight organic dusts with a job-exposure matrix
      (FINJEM). Cumulative exposure (CE) was calculated as a product of prevalence,
      level, and estimated duration of exposure. Standardised incidence ratios (SIR)
      and 95% confidence intervals (CI) adjusted for age, period, and social class were
      calculated for each organic dust using the economically active population as the
      reference. RESULTS: A total of 20 426 incident cases of respiratory cancer were
      observed. Slightly increased risk was observed among men exposed to wood dust for
      nasal cancer (SIR 1.42, 95% CI 0.79 to 2.44). For laryngeal cancer, men exposed
      to plant dust (mainly grain millers) had a raised SIR in the high exposure class
      (SIR 3.55, 95% CI 1.30 to 7.72). Men exposed to wood dust had a raised SIR for
      lung cancer, but only in the low exposure class (SIR 1.11, 95% CI 1.04 to 1.18).
      Women exposed to wood dust showed an increased SIR for mesotheliomas in the low
      exposure class (SIR 4.57, 95% CI 1.25 to 11.7) and some excess in the medium
      exposure category. CONCLUSIONS: Exposure to organic dusts is unlikely to be a
      major risk factor of respiratory cancer. Even exposure to wood dust which is a
      major exposure in Finland seems to have minor effect for nasal cancer. The
      authors found suggestive evidence that exposure to grain dust may increase the
      risk of laryngeal cancer, and some support to the hypothesis that exposure to
      textile dust, and to plant and animal dust (agricultural dusts) may decrease the
      risk of lung cancer.

PMID- 16601014
TI  - The frequency of workplace exacerbation among health maintenance organisation
      members with asthma.
AB  - OBJECTIVES: Workplace conditions can potentially contribute to the worsening of
      asthma, yet it is unclear what percentage of adults with asthma experience
      workplace exacerbation of symptoms. The objective of this investigation was to
      determine the prevalence of workplace exacerbation of asthma (WEA). METHODS:
      Adults with asthma aged 18-44 were enrolled into the baseline survey of a
      longitudinal study. Members of a health maintenance organisation were considered
      candidates for participation if they fulfilled membership, diagnostic, and
      treatment criteria based on automated review of electronic billing, claims, and
      pharmacy records. Diagnosis and treatment were confirmed by manual review of
      medical records. A telephone questionnaire was administered. A work related
      symptom score was assigned to each participant based on responses to questions
      about work related asthma symptoms, medication use, and symptom triggers. Blinded
      to participants' answers to these questions, two researchers independently
      reviewed the self-reported work histories and assigned exposure ratings. A final
      exposure score was then calculated. Participants with sufficient evidence for
      work related symptoms and exposure were classified as having WEA. RESULTS: Of the
      598 participants with complete data, 557 (93%) were working, and 136 (23%)
      fulfilled the criteria for WEA. Those with WEA were more likely to be male and to
      report that they had been bothered by asthma symptoms during the past seven days.
      CONCLUSIONS: Workplace exacerbation of asthma was common in this study
      population, occurring in over a fifth of these adults with asthma. Physicians
      should consider that work can contribute to the exacerbation of symptoms when
      treating adults with asthma.

PMID- 16601015
TI  - Associations of SF-36 mental health functioning and work and family related
      factors with intentions to retire early among employees.
AB  - OBJECTIVE: To examine the associations of mental health functioning (SF-36) and
      work and family related psychosocial factors with intentions to retire early.
      METHODS: Cross sectional survey data (n = 5037) from the Helsinki Health Study
      occupational cohort in 2001 and 2002 were used. Intentions to retire early were
      inquired with a question: "Have you considered retiring before normal retirement
      age?" Mental health functioning was measured by the Short Form 36 (SF-36) mental
      component summary (MCS). Work and family related psychosocial factors included
      job demands and job control, procedural and relational justice, conflicts between
      work and family, and social network size. Multinomial regression models were used
      to analyse the data. RESULTS: Poor mental health functioning, unfavourable
      psychosocial working conditions, and conflicts between work and family were
      individually related to intentions to retire early. After adjustments for all
      work and family related factors the odds ratio for low mental health functioning
      was halved (from OR = 6.05 to 3.67), but nevertheless the association between
      poor mental health functioning and strong intentions to retire early remained
      strong. CONCLUSIONS: These findings highlight not only the importance of low
      mental health and unfavourable working conditions but also the simultaneous
      impact of conflicts between work and family to employees' intentions to retire
      early.

PMID- 16601016
TI  - Early determinants of physical activity in adolescence: prospective birth cohort
      study.
AB  - OBJECTIVE: To examine the effects of early social, anthropometric, and
      behavioural variables on physical activity in adolescence. DESIGN: Prospective
      birth cohort study. SETTING: Pelotas, southern Brazil. PARTICIPANTS: 4453
      adolescents aged 10-12 years participating in the Pelotas 1993 birth cohort study
      (follow-up rate 87.5%). MAIN OUTCOME MEASURES: Sedentary lifestyle (< 300 minutes
      of physical activity per week) and median physical activity score (minutes per
      week). RESULTS: The prevalence of a sedentary lifestyle at age 10-12 years was
      58.2% (95% confidence interval 56.7% to 59.7%). Risk factors for a sedentary
      lifestyle in adolescence were female sex, high family income at birth, high
      maternal education at birth, and low birth order. Weight gain variables at ages 0
      1, 1-4, and 4-11 years and overweight at age 1 or 4 years were not significant
      predictors of physical activity. Levels of physical activity at age 4 years,
      based on maternal report, were inversely related to a sedentary lifestyle at age
      10-12 years. CONCLUSIONS: Physical activity in adolescence does not seem to be
      programmed by physiological factors in infancy. A positive association between
      birth order and activity may be due to greater intensity of play in childhood and
      adolescence. Tracking of physical activity from age 4 to 10-12 years, however,
      suggests that genetic factors or early habit formation may be important.

PMID- 16601017
TI  - Ecstasy and the antecedents of illicit drug use.

PMID- 16601018
TI  - Hepatitis B immunisation in Britain: time to change?

PMID- 16601019
TI  - The neglect of trauma surgery.

PMID- 16601020
TI  - Gillick or Fraser? A plea for consistency over competence in children.

PMID- 16601022
TI  - Swiss judge orders HIV positive woman to disclose partners' names.

PMID- 16601021
TI  - Life expectancy: women now on top everywhere.

PMID- 16601023
TI  - Another 2.4 million health professionals needed, says WHO.

PMID- 16601024
TI  - Chinese rules on transplantation do not go far enough.

PMID- 16601025
TI  - All older people should be guaranteed basic level of care.

PMID- 16601027
TI  - NICE says doctors could help 165,000 more smokers to quit.

PMID- 16601028
TI  - Doctors are failing to tell diabetic people about UK driving rules.

PMID- 16601030
TI  - Becker promotes condom use in Germany.

PMID- 16601031
TI  - Men who became ill in drug trial improve.

PMID- 16601034
TI  - Zambia scraps healthcare fees for poor rural people.

PMID- 16601037
TI  - Research identifies the most common cancers in teenagers and young adults.

PMID- 16601039
TI  - Lift patent barriers to increase access to medicines, says commission.

PMID- 16601042
TI  - Vaccines against cervical cancer provoke US controversy.

PMID- 16601043
TI  - Sleep disorders in children and adolescents.

PMID- 16601044
TI  - Hypertension and ethnic group.

PMID- 16601045
TI  - Testicular tumour presenting as gynaecomastia.

PMID- 16601046
TI  - Infections.

PMID- 16601049
TI  - Patients are not commodities.

PMID- 16601048
TI  - Referral management centres: promising innovations or Trojan horses?

PMID- 16601050
TI  - Not another innovation.

PMID- 16601051
TI  - Regulation of biomedical research in Africa.

PMID- 16601052
TI  - Do enforced bicycle helmet laws improve public health? Start with an assessment
      of the base problem, rather than assume a solution.

PMID- 16601053
TI  - Do enforced bicycle helmet laws improve public health? Evidence is conflicting.

PMID- 16601054
TI  - Do enforced bicycle helmet laws improve public health? Determining true
      effectiveness of safety measures.

PMID- 16601055
TI  - Disorders of sodium balance: hyponatraemia can occur during transurethral
      resection of prostate.

PMID- 16601056
TI  - Disorders of sodium balance: hyponatraemia and drug use (and abuse).

PMID- 16601057
TI  - Disorders of sodium balance: iatrogenic hyponatraemia--water overload and not
      enough potassium.

PMID- 16601058
TI  - Physical treatments have valuable role in osteoarthritis.

PMID- 16601059
TI  - Guantanamo: a call for action: good men need to do something.

PMID- 16601060
TI  - The CMA's legitimation crisis.

PMID- 16601061
TI  - Disorders of sodium balance: management of hypernatraemic dehydration differs in
      children.

PMID- 16601062
TI  - Disorders of sodium balance: hypothyroidism and hyponatraemia: an old wives'
      tale?

PMID- 16601063
TI  - Guantanamo: a call for action: would GMC dismiss a complaint against Guantanamo
      doctor?

PMID- 16601064
TI  - Guantanamo: a call for action: doctors should not treat detainees only to render
      them fit for further abuse.

PMID- 16601065
TI  - Comment on guidelines for the prophylaxis and treatment of methicillin-resistant
      Staphylococcus aureus (MRSA) infections in the UK.

PMID- 16601066
TI  - Reference intervals for hemoglobin A1c in pregnant women: data from an Italian
      multicenter study.
AB  - BACKGROUND: The reference intervals for hemoglobin A1c (Hb A1c) in pregnant women
      without diabetes are not well defined, and few examples of reference intervals
      established by networks of different laboratories are available. METHODS: Five
      Italian Diabetic Care Units were involved in the study. Data were collected from
      445 pregnant women without diabetes, selected on the basis of glucose challenge
      test results, and from 384 nonpregnant control women. The Hb A1c measurements
      were performed with HPLC systems aligned to the Diabetes Control and
      Complications Trial. Plasma glucose measurements were also performed locally.
      Both Hb A1c and glucose measurements were harmonized by running appropriate
      external quality assessment schemes. The reference intervals were calculated in
      terms of nonparametric 2.5th to 97.5th percentiles with 0.90 confidence
      intervals. RESULTS: The Hb A1c measurements were reproducible (CV = 2.0%) and
      accurate [mean (SE) difference from the target values, -0.10 (0.06)%]. Glucose
      measurements were also reproducible (mean CV = 3.2%) and accurate [difference
      from the target values, -0.01 (0.04) mmol/L]. To calculate common reference
      intervals, we merged the data collected in the different centers. The Hb A1c
      reference intervals were 4.0%-5.5% for pregnant nondiabetic women and 4.8%-6.2%
      for nonpregnant controls. CONCLUSIONS: Healthy pregnant women have lower Hb A1c
      concentrations than nonpregnant women. The reference intervals for Hb A1c in
      pregnant women should therefore be lower than those currently in use.

PMID- 16601067
TI  - Characterization of RNA in saliva.
AB  - BACKGROUND: We have previously shown that human mRNAs are present in saliva and
      can be used as biomarkers of oral cancer. In this study, we analyzed the
      integrity, sources, and stability of salivary RNA. METHODS: We measured the
      integrity of salivary RNA with reverse transcription followed by PCR (RT-PCR) or
      RT-quantitative PCR (RT-qPCR). To study RNA entry sites into the oral cavity, we
      used RT-PCR analysis of salivary RNA from the 3 major salivary glands, gingival
      crevice fluid, and desquamated oral epithelial cells. We measured stability of
      the salivary beta-actin mRNA by RT-qPCR of salivary RNA incubated at room
      temperature for different periods of time. We measured RNA association with other
      macromolecules by filtering saliva through pores of different sizes before
      performing RT-qPCR. To assess RNA-macromolecule interaction, we incubated saliva
      with Triton X-100 for different periods of time before performing RT-qPCR.
      RESULTS: In most cases, we detected partial- to full-length salivary mRNAs and
      smaller amounts of middle and 3' gene amplicons compared with the 5'. RNA was
      present in all oral fluids examined. Endogenous salivary beta-actin mRNA degraded
      more slowly than exogenous beta-actin mRNA, with half-lives of 12.2 and 0.4 min,
      respectively (P <0.001). Salivary RNA could not pass through 0.22 or 0.45 mum
      pores. Incubation of saliva with Triton X-100 accelerated degradation of salivary
      RNA. CONCLUSIONS: Saliva harbors both full-length and partially degraded forms of
      mRNA. RNA enters the oral cavity from different sources, and association with
      macromolecules may protect salivary RNA from degradation.

PMID- 16601068
TI  - Real-time nucleic acid sequence-based amplification assay to quantify changes in
      mitochondrial DNA concentrations in cell cultures and blood cells from HIV
      infected patients receiving antiviral therapy.
AB  - BACKGROUND: To study the clinical relevance of changes in mitochondrial DNA
      (mtDNA) in peripheral blood mononuclear cells (PBMCs) attributable to HIV
      infection and/or combination antiretroviral therapy (cART), a high-throughput
      molecular assay to quantify mtDNA is required. METHODS: We developed a
      quantitative real-time duplex nucleic acid sequence-based amplification assay in
      which both mtDNA and nuclear DNA are simultaneously amplified in 1 tube. The
      assay could accurately quantify mtDNA in a range of 15-1500 copies of mtDNA per 2
      genomic copies with an intrarun variation of 11% and an interrun variation of
      16%. We compared this real-time assay with the lactate/pyruvate ratios in
      fibroblasts incubated with glucose and exposed to zalcitabine. Additionally, we
      studied the effects of platelet contamination and the in vivo effects of cART on
      mtDNA in PBMCs from a small group of patients. RESULTS: Decreases in mtDNA
      preceded the increase in lactate/pyruvate ratios and vice versa when zalcitabine
      was eliminated from the culture. Platelets affected the mtDNA in PBMCs if >5
      platelets per PBMC were present. Within 12 weeks, mtDNA increased and remained
      increased in PBMCs from patients on continuous treatment with
      zidovudine/lamivudine/indinavir therapy (P = 0.03), but increased if patients
      were switched to stavudine/didanosine therapy (P = 0.008). CONCLUSION: After drug
      exposure, the mtDNA assay can detect changes in mtDNA concentrations in cell
      lines and PBMCs, when properly controlled for platelet effects, earlier than
      traditional assays.

PMID- 16601069
TI  - Replacing the mouse androgen receptor with human alleles demonstrates glutamine
      tract length-dependent effects on physiology and tumorigenesis in mice.
AB  - Polymorphism in the length of the N-terminal glutamine (Q) tract in the human
      androgen receptor (AR) has been implicated in affecting aspects of male health
      ranging from fertility to cancer. Extreme expansion of the tract underlies
      Kennedy disease, and in vitro the AR Q tract length correlates inversely with
      transactivation capacity. However, whether normal variation influences physiology
      or the etiology of disease has been controversial. To assess directly the
      functional significance of Q tract variation, we converted the mouse AR to the
      human sequence by germline gene targeting, introducing alleles with 12, 21, or 48
      glutamines. These three "humanized" AR (h/mAR) mouse lines were grossly normal in
      growth, behavior, fertility, and reproductive tract morphology. Phenotypic
      analysis revealed traits that varied subtly with Q tract length, including body
      fat amount and, more notably, seminal vesicle weight. Upon molecular analysis,
      tissue-specific differences in AR levels and target gene expression were detected
      between mouse lines. In the prostate, probasin, Nkx3.1, and clusterin mRNAs
      trended in directions predicted for inverse correlation of Q tract length with AR
      activation. Remarkably, when crossed with transgenic adenocarcinoma of mouse
      prostate (TRAMP) mice, striking genotype-dependent differences in prostate cancer
      initiation and progression were revealed. This link between Q tract length and
      prostate cancer, likely due to differential activation of AR targets,
      corroborates human epidemiological studies. This h/mAR allelic series in a
      homogeneous mouse genetic background allows examination of numerous physiological
      traits for Q tract influences and provides an animal model to test novel drugs
      targeted specifically to human AR.

PMID- 16601070
TI  - Single-chain, triple-domain gonadotropin analogs with disulfide bond mutations in
      the alpha-subunit elicit dual follitropin and lutropin activities in vivo.
AB  - The human glycoprotein hormones chorionic gonadotropin (CG), TSH, LH, and FSH are
      heterodimers composed of a common alpha-subunit and a hormone-specific beta
      subunit. The subunits assemble noncovalently early in the secretory pathway. LH
      and FSH are synthesized in the same cell (pituitary gonadotrophs), and several of
      the alpha-subunit sequences required for association with either beta-subunit are
      different. Nevertheless, no ternary complexes are observed for LH and FSH in
      vivo, i.e. both beta-subunits assembled with a single alpha-subunit. To address
      whether the alpha-subunit can interact with more than one beta-subunit
      simultaneously, we genetically linked the FSHbeta- and CGbeta-subunit genes to
      the common alpha-subunit, resulting in a single-chain protein that exhibited both
      activities in vitro. These studies also indicated that the bifunctional triple
      domain variant (FSHbeta-CGbeta-alpha), is secreted as two distinct bioactive
      populations each corresponding to a single activity, and each bearing the
      heterodimer-like contacts. Although the data are consistent with the known
      secretion events of gonadotropins from the pituitary, we could not exclude the
      possibility whether transient intermediates are generated in vivo in which the
      alpha-subunit shuttles between the two beta-subunits during early stages of
      accumulation in the endoplasmic reticulum. Therefore, constructs were engineered
      that would direct the synthesis of single-chain proteins completely devoid of
      heterodimer-like interactions but elicit both LH and FSH actions. These triple
      domain, single-chain chimeras contain the FSHbeta- and CGbeta-subunits and an
      alpha-subunit with cystine bond mutations (cys10-60 or cys32-84), which are known
      to prevent heterodimer formation. Here we show that, despite disrupting the
      intersubunit interactions between the alpha- and both CGbeta- and FSHbeta
      subunits, these mutated analogs exhibit both activities in vivo comparable to
      nonmutated triple-domain single chain. Such responses occurred despite the
      absence of quaternary contacts due to the disrupted bonds in the alpha-subunit.
      Thus, gonadotropin heterodimer assembly is critical for intracellular events,
      e.g. hormone-specific posttranslational modifications, but when heterodimers are
      present in the circulation, the alpha/beta-contacts are not a prerequisite for
      receptor recognition.

PMID- 16601071
TI  - The role of c-Jun N-terminal kinase, p38, and extracellular signal-regulated
      kinase in insulin-induced Thr69 and Thr71 phosphorylation of activating
      transcription factor 2.
AB  - The stimulation of cells with physiological concentrations of insulin induces a
      variety of responses, e.g. an increase in glucose uptake, induction of glycogen
      and protein synthesis, and gene expression. One of the determinants regulating
      insulin-mediated gene expression may be activating transcription factor 2 (ATF2).
      Insulin activates ATF2 by phosphorylation of Thr69 and Thr71 via a two-step
      mechanism, in which ATF2-Thr71 phosphorylation precedes the induction of ATF2
      Thr69+71 phosphorylation by several minutes. We previously found that in c-Jun N
      terminal kinase (JNK)-/- fibroblasts, cooperation of the ERK1/2 and p38 pathways
      is required for two-step ATF2-Thr69+71 phosphorylation in response to growth
      factors. Because JNK is also capable of phosphorylating ATF2, we assessed the
      involvement of JNK, ERK1/2 and p38 in the insulin-induced two-step ATF2
      phosphorylation in JNK-expressing A14 fibroblasts and 3T3L1-adipocytes. The
      induction of ATF2-Thr71 phosphorylation was sensitive to MAPK kinase (MEK) 1/2
      inhibition with U0126, and this phosphorylation coincided with nuclear
      translocation of phosphorylated ERK1/2. Use of the JNK inhibitor SP600125 or
      expression of dominant-negative JNK-activator SAPK kinase (SEK1) prevented the
      induction of ATF2-Thr69+71, but not ATF2-Thr71 phosphorylation by insulin. ATF2
      dependent transcription was also sensitive to SP-treatment. Abrogation of p38
      activation with SB203580 or expression of dominant-negative MKK6 had no
      inhibitory effect on these events. In agreement with this, the onset of ATF2
      Thr69+71 phosphorylation coincided with the nuclear translocation of
      phosphorylated JNK. Finally, in vitro kinase assays using nuclear extracts
      indicated that ERK1/2 preceded JNK translocation. We conclude that sequential
      activation and nuclear appearance of ERK1/2 and JNK, rather than p38, underlies
      the two-step insulin-induced ATF2 phosphorylation in JNK-expressing cells.

PMID- 16601072
TI  - Estrogen receptor alpha interacts with Galpha13 to drive actin remodeling and
      endothelial cell migration via the RhoA/Rho kinase/moesin pathway.
AB  - Sex steroids control cell movement and tissue organization; however, little is
      known of the involved mechanisms. This report describes the ongoing dynamic
      regulation by estrogen of the actin cytoskeleton and cell movement in human
      vascular endothelial cells that depends on rapid activation of the actin
      regulatory protein moesin. Moesin activation is triggered by the interaction of
      the C-terminal portion of cell membrane estrogen receptor alpha with the G
      protein Galpha(13), leading to activation of the small GTPase RhoA and of the
      downstream effector Rho-associated kinase. The resulting phosphorylation of
      moesin on Thr(558) is the means of moesin's binding to actin and the remodeling
      of the actin cytoskeleton. This cascade of events ensues within minutes of
      estradiol administration and results in changes in cell morphology and to the
      development of specialized cell membrane structures such as ruffles and
      pseudopodia that are necessary for cell movement. These findings expand our
      knowledge of the basis of estrogen's effects on human cells, including the
      regulation of actin assembly, cell movement and migration. They highlight novel
      pathways of signal transduction of estrogen receptor alpha through
      nontranscriptional mechanisms. Furthermore, exposure of this estrogen receptor
      dependent, nongenomic action of estrogen on human vascular endothelial cells is
      especially relevant to the present interest in the role of estrogen in
      cardiovascular protection.

PMID- 16601073
TI  - Ghrelin amplifies dopamine signaling by cross talk involving formation of growth
      hormone secretagogue receptor/dopamine receptor subtype 1 heterodimers.
AB  - Our objective is to determine the neuromodulatory role of ghrelin in the brain.
      To identify neurons that express the ghrelin receptor [GH secretagogue receptor
      (GHS-R)], we generated GHS-R-IRES-tauGFP mice by gene targeting. Neurons
      expressing the GHS-R exhibit green fluorescence and are clearly evident in the
      hypothalamus, hippocampus, cortex, and midbrain. Using immunohistochemistry in
      combination with green fluorescent protein fluorescence, we identified neurons
      that coexpress the dopamine receptor subtype 1 (D1R) and GHS-R. The potential
      physiological relevance of coexpression of these two receptors and the direct
      effect of ghrelin on dopamine signaling was investigated in vitro. Activation of
      GHS-R by ghrelin amplifies dopamine/D1R-induced cAMP accumulation. Intriguingly,
      amplification involves a switch in G protein coupling of the GHS-R from
      Galpha(11/q) to Galpha(i/o) by a mechanism consistent with agonist-dependent
      formation of GHS-R/D1R heterodimers. Most importantly, these results indicate
      that ghrelin has the potential to amplify dopamine signaling selectively in
      neurons that coexpress D1R and GHS-R.

PMID- 16601074
TI  - Thyroid-specific enhancer-binding protein/NKX2.1 is required for the maintenance
      of ordered architecture and function of the differentiated thyroid.
AB  - Thyroid-specific enhancer-binding protein (T/ebp)/Nkx2.1-null mouse thyroids
      degenerate by embryonic day (E) 12-13 through apoptosis whereas T/ebp/Nkx2.1
      heterogyzgous mice exhibit hypothyroidism with elevated TSH levels. To understand
      the role of T/ebp/Nkx2.1 in the adult thyroid, a thyroid follicular cell-specific
      conditional knockout (KO) mouse line, T/ebp(fl/fl);TPO-Cre, was established that
      expresses Cre recombinase under the human thyroid peroxidase (TPO) gene promoter.
      These mice appeared to be healthy and exhibited loss of T/ebp/Nkx2.1 expression
      in many, but not all, thyroid follicular cells as determined by
      immunohistochemistry and real-time PCR, thus presenting a T/ebp-thyroid
      conditional hypomorphic mice. Detailed analysis of the thyroids from
      T/ebp(fl/fl), T/ebp(fl/fl);TPO-Cre, and T/ebp(fl/ko) mice, where the latter mouse
      line is derived from crosses with the original T/ebp/Nkx2.1-heterozygous mice,
      revealed that T/ebp(fl/fl);TPO-Cre mice can be classified into two groups with
      different phenotypes: one having atrophic/degenerative thyroid follicles with
      frequent presence of adenomas and extremely high serum TSH levels, and the other
      having an altered thyroid structure with reduced numbers of extraordinary dilated
      follicles consisting of excessive numbers of follicular cells as compared with
      those usually found in the normal thyroid. The latter phenotype was also observed
      in aged T/ebp(fl/ko) mouse thyroids. In vitro three-dimensional thyroid primary
      cultures using thyroids from T/ebp(fl/fl);TPO-Cre, T/ebp(fl/ko), and T/ebp(fl/fl)
      mice, and the latter treated with recombinant adenovirus with and without Cre
      expression, demonstrated that only cells from T/ebp(fl/fl) mice without adeno-Cre
      treatment formed follicular structures. Taken together, these results suggest
      that T/ebp/Nkx2.1 is required for maintenance of the normal architecture and
      function of differentiated thyroids.

PMID- 16601075
TI  - A systematic review of the clinical effects of reducing dialysate fluid
      temperature.
AB  - BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of
      haemodialysis. Reducing the temperature of the dialysis fluid is a simple
      therapeutic strategy but is relatively underused. This may be due to concerns
      regarding its effects on symptoms and dialysis adequacy. We performed a
      systematic review of the literature to examine the effects of cool dialysis on
      intradialytic blood pressure, and to assess its safety in terms of thermal
      symptoms and small solute clearance. METHODS: We searched the Cochrane Central
      Register of Controlled Trials, Medline, Embase, Cumulative Index to Nursing and
      Allied Health Literature, databases of ongoing trials, the contents of four major
      renal journals as well as hand-searching reference lists. We included all
      prospective randomized studies that compared any technique of reducing dialysate
      temperature with standard bicarbonate dialysis. These techniques included an
      empirical, fixed reduction of dialysate temperature or use of a biofeedback
      temperature-control device (BTM) to deliver isothermic dialysis or programmed
      patient cooling. RESULTS: A total of 22 studies comprising 408 patients were
      included (16 studies examined a fixed empirical temperature reduction and six
      examined BTM). All studies were of crossover design and relatively short
      duration. IDH occurred 7.1 (95% CI, 5.3-8.9) times less frequently with cool
      dialysis (both fixed reduction and BTM). Post-dialysis mean arterial pressure was
      higher with cool-temperature dialysis by 11.3 mmHg (95% CI, 7.7-15.0). No studies
      reported that cool dialysis led to a reduction in dialysis adequacy as assessed
      by urea clearance. The frequency and severity of thermal-related symptoms were
      generally reported inadequately. CONCLUSIONS: Reducing the temperature of the
      dialysate is an effective intervention to reduce the frequency of IDH and does
      not adversely affect dialysis adequacy. This applies to the fixed reduction of
      dialysate temperature and BTM. It remains unclear as to what extent cool
      temperature dialysis causes intolerable cold symptoms during dialysis. There are
      no trials comparing fixed empirical temperature reduction with BTM, and no trials
      examining the long-term effects of cool dialysis on patient outcomes.

PMID- 16601076
TI  - Xenograft rejection--all that glitters is not Gal.

PMID- 16601077
TI  - Assessment of contractility of purified smooth muscle cells derived from
      embryonic stem cells.
AB  - The aims of this study were to develop a method for deriving purified populations
      of contractile smooth muscle cells (SMCs) from embryonic stem cells (ESCs) and to
      characterize their function. Transgenic ESC lines were generated that stably
      expressed a puromycin-resistance gene under the control of either a smooth muscle
      alpha-actin (SMalphaAlpha) or smooth muscle-myosin heavy chain (SM-MHC) promoter.
      Negative selection, either overnight or for 3 days, was then used to purify SMCs
      from embryoid bodies. Purified SMCs expressed multiple SMC markers by
      immunofluorescence, immunoblotting, quantitative reverse transcription-polymerase
      chain reaction, and flow cytometry and were designated APSCs (SMalphaAlpha
      puromycin-selected cells) or MPSCs (SM-MHC-puromycin-selected cells),
      respectively. Both SMC lines displayed agonist-induced Ca(2+) transients,
      expressed functional Ca(2+) channels, and generated contractile force when
      aggregated within collagen gels and stimulated with vasoactive agonists, such as
      endothelin-1, or in response to depolarization with KCl. Importantly,
      subcutaneous injection of APSCs or MPSCs subjected to 18 hours of puromycin
      selection led to the formation of teratomas, presumably due to residual
      contamination by pluripotent stem cells. In contrast, APSCs or MPSCs subjected to
      prolonged puromycin selection for 3 days did not form teratomas in vivo. These
      studies describe for the first time a method for generating relatively pure
      populations of SMCs from ESCs which display appropriate excitation and
      contractile responses to vasoactive agonists. However, studies also indicate the
      potential for teratoma development in ESC-derived cell lines, even after
      prolonged differentiation, highlighting the critical requirement for efficient
      methods of separating differentiated cells from residual pluripotent precursors
      in future studies that use ESC derivatives, whether SMC or other cell types, in
      tissue engineering applications.

PMID- 16601078
TI  - Osteogenic differentiation of noncultured immunoisolated bone marrow-derived
      CD105+ cells.
AB  - The culture expansion of human mesenchymal stem cells (hMSCs) may alter their
      characteristics and is a costly and time-consuming stage. This study demonstrates
      for the first time that immunoisolated noncultured CD105-positive (CD105(+))
      hMSCs are multipotent in vitro and exhibit the capacity to form bone in vivo.
      hMSCs are recognized as promising tools for bone regeneration. However, the
      culture stage is a limiting step in the clinical setting. To establish a simple,
      efficient, and fast method for applying these cells for bone formation, a
      distinct population of CD105(+) hMSCs was isolated from bone marrow (BM) by using
      positive selection based on the expression of CD105 (endoglin). The
      immunoisolated CD105(+) cell fraction represented 2.3% +/- 0.45% of the
      mononuclear cells (MNCs). Flow cytometry analysis of freshly immunoisolated
      CD105(+) cells revealed a purity of 79.7% +/- 3.2%. In vitro, the CD105(+) cell
      fraction displayed significantly more colony-forming units-fibroblasts (CFU-Fs;
      6.3 +/- 1.4) than unseparated MNCs (1.1 +/- 0.3; p < .05). Culture-expanded
      CD105(+) cells expressed CD105, CD44, CD29, CD90, and CD106 but not CD14, CD34,
      CD45, or CD31 surface antigens, and these cells were able to differentiate into
      osteogenic, chondrogenic, and adipogenic lineages. In addition, freshly
      immunoisolated CD105(+) cells responded in vivo to recombinant bone morphogenetic
      protein-2 by differentiating into chondrocytes and osteoblasts. Genetic
      engineering of freshly immunoisolated CD105(+) cells was accomplished using
      either adenoviral or lentiviral vectors. Based on these findings, it is proposed
      that noncultured BM-derived CD105(+) hMSCs are osteogenic cells that can be
      genetically engineered to induce tissue generation in vivo.

PMID- 16601079
TI  - Circulating progenitor cells are reduced in patients with severe lung disease.
AB  - Patients with chronic severe lung disease are prone to develop pulmonary vascular
      remodeling, possibly through pulmonary endothelial dysfunction. Circulating
      endothelial progenitor cells (EPCs) are involved in maintenance of endothelial
      homeostasis. The aim of this study was to assess whether obstructive and
      restrictive lung diseases are associated with modification of EPC number in
      peripheral blood. The study was cross-sectional and involved patients with
      obstructive (n = 15) and restrictive (n = 15) lung disease on oxygen therapy and
      15 control subjects. Circulating EPCs were defined by the surface expression of
      CD34, CD133, and kinase-insert domain receptor. Results from spirometric tests,
      blood gas analyses, and blood cell counts have been related to EPC numbers.
      Patients with chronic hypoxia and severe lung disease showed lower levels of all
      progenitors than do control subjects. A consensual further reduction of EPC was
      found in restrictive patients in comparison with obstructive patients. Among
      restrictive patients, EPC reduction was related to reduced lung volumes and
      impaired alveolo-arterial diffusion, whereas progenitor cell levels were directly
      related to erythrocyte number. Considering obstructive patients, significant
      correlations were found between progenitor cell levels and bronchial obstruction
      and between progenitor cell levels and arterial oxygen tension. These findings
      demonstrate a reduction of EPCs in patients with chronic lung disease and long
      lasting hypoxia. This alteration was more evident in restrictive patients and
      correlated to disease severity. Depletion of circulating EPCs may be involved in
      altered endothelial homeostasis of pulmonary circulation in these disorders.

PMID- 16601080
TI  - In vitro profiling of the endocrine-disrupting potency of brominated flame
      retardants.
AB  - Over the last few years, increasing evidence has become available that some
      brominated flame retardants (BFRs) may have endocrine-disrupting (ED) potencies.
      The goal of the current study was to perform a systematic in vitro screening of
      the ED potencies of BFRs (1) to elucidate possible modes of action of BFRs in man
      and wildlife and (2) to classify BFRs with similar profiles of ED potencies. A
      test set of 27 individual BFRs were selected, consisting of 19 polybrominated
      diphenyl ether congeners, tetrabromobisphenol-A, hexabromocyclododecane, 2,4,6
      tribromophenol, ortho-hydroxylated brominated diphenyl ether 47, and
      tetrabromobisphenol-A-bis(2,3)dibromopropyl ether. All BFRs were tested for their
      potency to interact with the arylhydrocarbon receptor, androgen receptor (AR),
      progesterone receptor (PR), and estrogen receptor. In addition, all BFRs were
      tested for their potency to inhibit estradiol (sulfation by estradiol
      sulfotransferase (E2SULT), to interfere with thyroid hormone 3,3',5
      triiodothyronine (T3)-mediated cell proliferation, and to compete with T3
      precursor thyroxine for binding to the plasma transport protein transthyretin
      (TTR). The results of the in vitro screening indicated that BFRs have ED
      potencies, some of which had not or only marginally been described before (AR
      antagonism, PR antagonism, E2SULT inhibition, and potentiation of T3-mediated
      effects). For some BFRs, the potency to induce AR antagonism, E2SULT inhibition,
      and TTR competition was higher than for natural ligands or clinical drugs used as
      positive controls. Based on their similarity in ED profiles, BFRs were classified
      into five different clusters. These findings support further investigation of the
      potential ED effects of these environmentally relevant BFRs in man and wildlife.

PMID- 16601081
TI  - Interactions of polybrominated diphenyl ethers with the aryl hydrocarbon receptor
      pathway.
AB  - Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants that have
      been in use as additives in various consumer products. Structural similarities of
      PBDEs with other polyhalogenated aromatic hydrocarbons that show affinity for the
      aryl hydrocarbon receptor (AhR), such as some polychlorinated biphenyls, raised
      concerns about their possible dioxin-like properties. We studied the ability of
      environmentally relevant PBDEs (BDE-47, -99, -100, -153, -154, and -183) and the
      "planar" congener BDE-77 to bind and/or activate the AhR in stably transfected
      rodent hepatoma cell lines with an AhR-responsive enhanced green fluorescent
      protein (AhR-EGFP) reporter gene (H1G1.1c3 mouse and H4G1.1c2 rat hepatoma). 7
      Ethoxyresorufin-O-deethylation (EROD) was used as a marker for CYP1A1 activity.
      Dose- and bromination-specific inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD)-induced responses was measured by their ability to inhibit the induction
      of AhR-EGFP expression and EROD activity. Individual exposure to these PBDEs did
      not result in any increase in induction of AhR-EGFP or CYP1A1 activity. The lower
      brominated PBDEs showed the strongest inhibitory effect on TCDD-induced
      activities in both cell lines. While the highest brominated PBDE tested, BDE-183,
      inhibited EROD activity, it did not affect the induction of AhR-EGFP expression.
      Similar findings were observed after exposing stably transfected human hepatoma
      (xenobiotic response element [XRE]-HepG2) cells to these PBDEs, resulting in a
      small but statically significant agonistic effect on XRE-driven luciferase
      activity. Co-exposure with TCDD resulted again in antagonistic effects,
      confirming that the inhibitory effect of these PBDEs on TCDD-induced responses
      was not only due to direct interaction at receptor level but also at DNA-binding
      level. This antagonism was confirmed for BDE-99 in HepG2 cells transiently
      transfected with a Gal4-AhR construct and the corresponding Gal4-Luc reporter
      gene. In addition, a chromatin immunoprecipitation assay further confirmed that
      BDE-99 could bind to the AhR and activate the AhR nuclear translocation and
      dioxin responsive element (DRE) binding in the context of the CYP1A1 promoter.
      However, the transactivation function of the BDE-99-activated AhR seems to be
      very weak. These combined results suggest that PBDEs do bind but not activate the
      AhR-AhR nuclear translocator protein-XRE complex.

PMID- 16601082
TI  - A system-based approach to interpret dose- and time-dependent microarray data:
      quantitative integration of gene ontology analysis for risk assessment.
AB  - Although microarray technology has emerged as a powerful tool to explore
      expression levels of thousands of genes or even complete genomes after exposure
      to toxicants, the functional interpretation of microarray data sets still
      represents a time-consuming and challenging task. Gene ontology (GO) and pathway
      mapping have both been shown to be powerful approaches to generate a global view
      of biological processes and cellular components impacted by toxicants. However,
      current methods only allow for comparisons across two experimental settings at
      one particular time point. In addition, the resulting annotations are presented
      in extensive gene lists with minimal or limited quantitative information, data
      that are crucial in the application of toxicogenomic data for risk assessment. To
      facilitate quantitative interpretation of dose- or time-dependent genomic data,
      we propose to use combined average raw gene expression values (e.g., intensity or
      ratio) of genes associated with specific functional categories derived from the
      GO database. We developed an extended program (GO-Quant) to extract quantitative
      gene expression values and to calculate the average intensity or ratio for those
      significantly altered by functional gene category based on MAPPFinder results. To
      demonstrate its application, we applied this approach to a previously published
      dose- and time-dependent toxicogenomic data set (J. F. Dillman et al., 2005,
      Chem. Res. Toxicol. 18, 28-34). Our results indicate that the above systems
      approach can describe quantitatively the degree to which functional gene systems
      change across dose or time. Additionally, this approach provides a robust
      measurement to illustrate results compared to single-gene assessments and enables
      the user to calculate the corresponding ED(50) for each specific functional GO
      term, important for risk assessment.

PMID- 16601083
TI  - Structural determinants of 4-chloro-m-cresol required for activation of ryanodine
      receptor type 1.
AB  - 4-Chloro-m-cresol (4-CmC) is a clinically relevant activator of the intracellular
      Ca2+ release channel, the ryanodine receptor isoform 1 (RyR1). In this study, the
      chemical moieties on the 4-CmC molecule required for its activation of RyR1 were
      determined using structure-activity relationship analysis with a set of
      commercially available 4-CmC analogs. Separate compounds each lacking one of the
      three functional groups of 4-CmC (1-hydroxyl, 3-methyl, or 4-chloro) were poor
      activators of RyR1. Substitution of different chemical groups for the 1-hydroxyl
      of 4-CmC resulted in compounds that were poor activators of RyR1, suggesting that
      the hydroxyl group is preferred at this position. Substitution of hydrophobic
      groups at the 3-position enhanced bioactivity of the compound relative to 4-CmC,
      whereas substitution with hydrophilic groups abolished bioactivity. Likewise, 4
      CmC analogs with hydrophobic groups substituted into the 4-position enhanced
      bioactivity, whereas hydrophilic or charged groups diminished bioactivity. 4-CmC
      analogs containing a single hydrophobic group at either the 3- or 4-position as
      well as 3,5-disubstituted or 3,4,5-trisubstituted phenols were also effective
      activators of RyR1. These results indicate that the 1-hydroxyl group of 4-CmC is
      required for activation of RyR1 and that hydrophobic groups at the 3,4- and 5
      positions are preferred. These findings suggest that the 4-CmC binding site on
      RyR1 most likely consists of a hydrophilic region to interact with the 1-hydroxyl
      as well as a hydrophobic region(s) to interact with chemical groups at the 3-
      and/or 4-positions of 4-CmC.

PMID- 16601084
TI  - Long term effects of antenatal betamethasone on lung function: 30 year follow up
      of a randomised controlled trial.
AB  - BACKGROUND: Antenatal betamethasone is routinely used for the prevention of
      neonatal respiratory distress syndrome in preterm infants. However, little is
      known of the long term effects of exposure to antenatal betamethasone on lung
      function in adulthood. METHODS: Five hundred and thirty four 30 year olds whose
      mothers had participated in the first and largest randomised controlled trial of
      antenatal betamethasone were followed. Lung function was assessed by portable
      spirometric testing. The prevalence of asthma symptoms was assessed using the
      European Community Respiratory Health Survey questionnaire. RESULTS: Fifty (20%)
      betamethasone exposed and 53 (19%) placebo exposed participants met the criteria
      for current asthma (relative risk 0.98 (95% CI 0.74 to 1.30), p = 0.89). 181
      betamethasone exposed and 202 placebo exposed participants had acceptable
      spirometric data. There were no differences in lung function between
      betamethasone and placebo exposed groups (mean (SD) forced vital capacity in the
      betamethasone and placebo groups 105.9 (12.0) v 106.6 (12.6)% predicted,
      difference = -0.7 (95% CI -3.2 to 1.8), p = 0.59; mean (SD) forced expiratory
      volume in 1 second in the betamethasone and placebo groups 98.9 (13.4) v 98.5
      (13.6)% predicted, difference = 0.3 (95% CI -2.4 to 3.1, p = 0.80)). CONCLUSIONS:
      Antenatal exposure to a single course of betamethasone does not alter lung
      function or the prevalence of wheeze and asthma at age 30.

PMID- 16601085
TI  - Capsaicin cough sensitivity in bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is a suppurative airway disease characterised by
      persistent cough and sputum production associated with bronchial dilatation. A
      study was undertaken to determine whether cough sensitivity is increased in
      bronchiectatic patients. METHODS: Twenty two patients with bronchiectasis and 20
      healthy non-smoking controls matched for age and sex were recruited into the
      study. Quality of life (Leicester Cough Questionnaire score), total cough symptom
      score, and extent of bronchiectasis on HRCT scans were recorded. Cough
      sensitivity was assessed using incremental inhalation of capsaicin
      concentrations; the concentration at which 5 or more coughs occurred (C5) was
      recorded. RESULTS: Patients with bronchiectasis had increased sensitivity to
      capsaicin compared with controls (mean (SE) log10 C5 1.22 (0.20) v 1.89 (0.21);
      p<0.03). Capsaicin sensitivity correlated positively with the Leicester Cough
      Questionnaire score (r = 0.64; p = 0.005) and inversely with the total cough
      symptom score (r = -0.58; p = 0.004), but not with the extent of the disease. It
      also correlated with forced expiratory volume in 1 second (FEV1) in litres (r =
      0.58; p = 0.005) but not with FEV1 % predicted. Capsaicin sensitivity was not
      related to the presence of infected sputum or to corticosteroid or bronchodilator
      use. CONCLUSIONS: : Patients with bronchiectasis have a sensitive cough reflex
      which reflects the severity of cough symptoms. A measure of cough severity could
      be part of health assessment for patients with bronchiectasis.

PMID- 16601086
TI  - Non-tuberculous mycobacteria in end stage cystic fibrosis: implications for lung
      transplantation.
AB  - BACKGROUND: WC and NS contributed equally. Non-tuberculous mycobacteria (NTM)
      frequently colonise patients with end stage cystic fibrosis (CF), but its impact
      on the course of the disease following lung transplantation is unknown. METHODS:
      Lung transplant recipients with CF who underwent lung transplantation at our
      institution between January 1990 and May 2003 (n=146) and CF patients awaiting
      lung transplantation in May 2003 (n=31) were studied retrospectively. RESULTS:
      The prevalence rate of NTM isolated from respiratory cultures in patients with
      end stage CF referred for lung transplantation was 19.7%, compared with a
      prevalence rate of 13.7% for NTM isolates in CF lung transplant recipients. The
      overall prevalence of invasive NTM disease after lung transplantation was low
      (3.4%) and was predicted most strongly by pre-transplant NTM isolation (p=0.001,
      Fisher's exact test, odds ratio (OR) 6.13, 95% CI 3.2 to 11.4). This association
      was restricted to Mycobacterium abscessus (p = 0.005, Fisher's exact test, OR
      7.45, 95% CI 2.9 to 16.9). While NTM disease caused significant morbidity in a
      small number of patients after transplantation, it was successfully treated and
      did not influence the post-transplant course of the disease. CONCLUSION: The
      isolation of NTM before transplantation in CF patients should not be an exclusion
      criterion for lung transplantation, but it may alert the clinician to patients at
      risk of recurrence following transplantation.

PMID- 16601087
TI  - Pseudomembranous colitis in four patients with cystic fibrosis following lung
      transplantation.
AB  - Pseudomembranous colitis is an uncommon complication in patients with cystic
      fibrosis, despite the use of multiple high-dose antibiotic regimens and the
      frequency of hospital admissions. Four patients from a total of 137 patients with
      cystic fibrosis undergoing lung transplantation are described who developed
      fulminant pseudomembranous colitis. Initial presentation was variable and the
      mortality rate was 50% despite urgent colectomy. In one case the presenting
      abdominal distension was thought to be due to meconium ileus equivalent. It is
      concluded that Clostridium difficile colitis may be a difficult diagnosis in
      patients with cystic fibrosis and follows a fulminant course after lung
      transplantation.

PMID- 16601088
TI  - Performance of a whole blood interferon gamma assay for detecting latent
      infection with Mycobacterium tuberculosis in children.
AB  - BACKGROUND: The diagnosis of latent Mycobacterium tuberculosis (MTB) infection
      with a tuberculin skin test (TST) in children is complicated by the potential
      influence of prior exposure to Bacille Calmette Geurin (BCG) vaccination or
      environmental mycobacteria. A whole blood assay has recently been developed to
      quantitatively measure interferon gamma (IFN-gamma) production by lymphocytes
      specific to the MTB antigens ESAT-6 and CFP-10, but its use and assessment in
      children has been limited. A study was undertaken to compare the performance of
      the whole blood IFN-gamma assay with the TST in diagnosing latent tuberculosis
      (TB) infection or TB disease in children in routine clinical practice. METHODS:
      One hundred and six children with a high risk of latent TB infection or TB
      disease were enrolled in the study. High risk was defined as contact with TB
      disease, clinical suspicion of TB disease, or recent arrival from an area of high
      TB prevalence. The whole blood IFN-gamma assay was undertaken in 101 children.
      RESULTS: Seventeen (17%) of the 101 assays yielded inconclusive results due to
      failure of positive or negative control assays. There was poor correlation
      between the whole blood IFN-gamma assay and the TST (kappa statistic 0.3) with 26
      (70%) of the 37 children defined as latent TB infection by TST having a negative
      whole blood IFN-gamma assay. There were no instances of a positive whole blood
      IFN-gamma assay with a negative TST. Mitogen (positive) control IFN-gamma
      responses were significantly correlated with age (Spearman's coefficient = 0.53,
      p<0.001) and, in children with latent TB infection identified by TST, those with
      a positive IFN-gamma assay were older (median 12.9 v 6.92 years, respectively, p
      = 0.007). The whole blood IFN-gamma assay was positive in all nine children with
      TB disease. CONCLUSION: There was poor agreement between the whole blood IFN
      gamma assay and TST for the diagnosis of latent TB. The whole blood IFN-gamma
      assay may have lower sensitivity than the TST in diagnosing TB infection in
      children. A significant proportion of whole blood IFN-gamma assays fail when used
      as a screening assay in routine practice.

PMID- 16601089
TI  - Differences in motor activation of voluntary and reflex cough in humans.
AB  - OBJECTIVES: To study motor activation patterns of voluntary and reflex cough
      adjusted for cough flow rates. METHODS: Surface electromyography (EMG) and cough
      flow rate were measured in 10 healthy volunteers. Voluntary cough was assessed
      for 20 efforts in each quintile of increasing cough flow rate. Reflex cough was
      assessed for 25 efforts produced by nebulised l-tartaric acid. EMG was recorded
      over the expiratory (rectus abdominis, obliques, lower intercostals) and
      accessory (trapezius, pectoralis major, deltoid, latissimus dorsi) muscles. EMG
      activity, burst duration and onset were compared for each quintile of voluntary
      cough, and between voluntary and reflex cough matched for cough flow rate.
      RESULTS: EMG activity and burst duration of expiratory and accessory muscles
      during voluntary cough increased in proportion to cough flow. Expiratory muscles
      had longer EMG burst duration (difference 68 ms (95% CI 34 to 102), p<0.01) and
      earlier onset of EMG activity (difference 44 ms (95% CI 20 to 68), p<0.0001)
      compared with accessory muscles. EMG activity in all muscles was increased (mean
      110.2% v 56.1%, p<0.001) and burst duration (mean 206 ms v 280 ms, p = 0.013)
      decreased in reflex cough compared with voluntary cough of equal flow rate. There
      were no differences in EMG onset (difference 8 ms (95% CI 25 to -9) or burst
      duration (difference 27 ms (95% CI 58 to -4) between expiratory and accessory
      muscles. CONCLUSIONS: Functional organisation of motor activity differs between
      voluntary and reflex cough. Voluntary cough is characterised by sequential
      activation whereas reflex cough is associated with early and simultaneous
      activation of expiratory and accessory muscles.

PMID- 16601090
TI  - Mast cell migration to Th2 stimulated airway smooth muscle from asthmatics.
AB  - BACKGROUND: Mast cell microlocalisation within the airway smooth muscle (ASM)
      bundle is an important determinant of the asthmatic phenotype. We hypothesised
      that mast cells migrate towards ASM in response to ASM derived chemokines.
      METHODS: Primary ASM cultures from subjects with and without asthma were
      stimulated with interleukin (IL)-1beta, IL-4, and IL-13 alone and in combination.
      Mast cell chemotaxis towards these ASM supernatants was investigated, and the
      chemotaxins mediating migration by using specific blocking antibodies for stem
      cell factor (SCF) and the chemokine receptors CCR3, CXCR1, 3 and 4 as well as the
      Gi inhibitor pertussis toxin and the tyrosine kinase inhibitor genistein were
      defined. The concentrations of CCL11, CXCL8, CXCL10, TGF-beta, and SCF in the
      supernatants were measured and the effect of non-asthmatic ASM supernatants on
      the mast cell chemotactic activity of asthmatic ASM was examined. RESULTS: Human
      lung mast cells and HMC-1 cells migrated towards Th2 stimulated ASM from
      asthmatics but not non-asthmatics. Mast cell migration was mediated through the
      combined activation of CCR3 and CXCR1. CCL11 and CXCL8 expression by ASM
      increased markedly after stimulation, but was similar in those with and without
      asthma. ASM supernatants from non-asthmatics inhibited mast cell migration
      towards the asthmatic ASM supernatant. CONCLUSION: Th2 stimulated ASM from
      asthmatics is chemotactic for mast cells. Non-asthmatic ASM releases a mediator
      or mediators that inhibit mast cell migration towards stimulated asthmatic ASM.
      Specifically targeting mast cell migration into the ASM bundle may provide a
      novel treatment for asthma.

PMID- 16601091
TI  - Survival after resection for primary lung cancer: a population based study of
      3211 resected patients.
AB  - BACKGROUND: Very few population based results have been presented for survival
      after resection for lung cancer. The purpose of this study was to present long
      term survival after resection and to quantify prognostic factors for survival.
      METHODS: All lung cancer patients diagnosed in Norway in 1993-2002 were reported
      to the Cancer Registry of Norway (n = 19 582). A total of 3211 patients underwent
      surgical resection and were included for analysis. Supplementary information from
      hospitals (including co-morbidity data) was collected for patients diagnosed in
      1993-8. Five year observed and relative survival was analysed for patients
      diagnosed and operated in 1993-9. Factors believed to influence survival were
      analysed by a Cox proportional hazard regression model. RESULTS: Five year
      relative survival in the period 1993-9 was 46.4% (n = 2144): 58.4% for stage I
      disease (n = 1375), 28.4% for stage II (n = 532), 15.1% for IIIa (n = 133), 24.1%
      for IIIb (n = 63), and 21.1% for stage IV disease (n = 41). The high survival in
      stage IIIb and IV was due to the contribution of multiple tumours. Cox regression
      analysis identified male sex, higher age, procedures other than upper and middle
      lobectomy, histologies such as adenocarcinoma and large cell carcinoma, surgery
      on the right side, infiltration of resection margins, and larger tumour size as
      non-favourable prognostic factors. CONCLUSIONS: Survival was favourable for
      resected patients in a population based group including subgroups such as elderly
      patients, those with advanced stage, small cell lung cancer, tumours with nodal
      invasion, and patients with multiple tumours. These results question the validity
      of the current TNM system for lung cancer with regard to tumour size and
      categorization of multiple tumours.

PMID- 16601092
TI  - Improved survival for HIV infected patients with severe Pneumocystis jirovecii
      pneumonia is independent of highly active antiretroviral therapy.
AB  - BACKGROUND: Despite a decline in incidence of Pneumocystis jirovecii pneumonia
      (PCP), severe PCP continues to be a common cause of admission to the intensive
      care unit (ICU) where mortality remains high. A study was undertaken to examine
      the outcome from intensive care for patients with PCP and to identify prognostic
      factors. METHODS: A retrospective cohort study was conducted of HIV infected
      adults admitted to a university affiliated hospital ICU between November 1990 and
      October 2005. Case note review collected information on demographic variables,
      use of prophylaxis and highly active antiretroviral therapy (HAART), and hospital
      course. The main outcome was 1 month mortality, either on the ICU or in hospital.
      RESULTS: Fifty nine patients were admitted to the ICU on 60 occasions. Thirty
      four patients (57%) required mechanical ventilation. Overall mortality was 53%.
      No patient received HAART before or during ICU admission. Multivariate analysis
      showed that the factors associated with mortality were the year of diagnosis
      (before mid 1996 (mortality 71%) compared with later (mortality 34%; p = 0.008)),
      age (p = 0.016), and the need for mechanical ventilation and/or development of
      pneumothorax (p = 0.031). Mortality was not associated with sex, ethnicity, prior
      receipt of sulpha prophylaxis, haemoglobin, serum albumin, CD4 count, PaO2, A-aO2
      gradient, co-pathology in bronchoscopic lavage fluid, medical co-morbidity,
      APACHE II score, or duration of mechanical ventilation. CONCLUSIONS: Observed
      improved outcomes from severe PCP for patients admitted to the ICU occurred in
      the absence of intervention with HAART and probably reflect general improvements
      in ICU management of respiratory failure and ARDS rather than improvements in the
      management of PCP.

PMID- 16601093
TI  - Diagnostic value of serological tests against Pseudomonas aeruginosa in a large
      cystic fibrosis population.
AB  - BACKGROUND: Serological methods to monitor Pseudomonas aeruginosa colonisation in
      patients with cystic fibrosis (CF) are advocated but the diagnostic value of a
      commercially available P aeruginosa antibody test to detect early and chronic P
      aeruginosa colonisation in a non-research setting has not been assessed. METHODS:
      Colonisation with P aeruginosa was estimated by regular culture of sputum or
      oropharyngeal swabs during three consecutive years in 220 patients with CF aged 0
      65 years. Commercially available ELISA tests with three P aeruginosa antigens
      (elastase, exotoxin A, alkaline protease) were performed at the end of the study
      period. In a subgroup of 57 patients (aged 4-14 years) serological tests were
      performed annually. RESULTS: Using culture as the reference standard, the ELISA
      tests using the advised cut off values had a sensitivity of 79% and a specificity
      of 89% for chronic colonisation. Receiver-operator characteristic curves were
      created to optimise cut off values. Applying these new cut off values resulted in
      a sensitivity of 96% and a specificity of 79%. All three individual serological
      tests discriminated well between the absence and presence of chronic P aeruginosa
      colonisation. The sensitivity of the individual antibody test was 87% for
      elastase, 79% for exotoxin A, and 76% for alkaline protease. First colonisation
      was preceded by positive serological results in only five of 13 patients (38%).
      CONCLUSION: In patients with CF, serological tests using specific antigens are
      sensitive for diagnosing chronic P aeruginosa colonisation. However, the failure
      of serological tests to detect early colonisation in young patients emphasises
      the need for continued reliance on cultures.

PMID- 16601094
TI  - Extracellular thioredoxin levels are increased in patients with acute lung
      injury.
AB  - BACKGROUND: Acute lung injury (ALI) and its extreme manifestation the acute
      respiratory distress syndrome (ARDS) complicate a wide variety of serious medical
      and surgical conditions. Thioredoxin is a small ubiquitous thiol protein with
      redox/inflammation modulatory properties relevant to the pathogenesis of ALI. We
      therefore investigated whether thioredoxin is raised extracellulary in patients
      with ALI and whether the extent of any increase is dependent upon the nature of
      the precipitating insult. METHODS: Bronchoalveolar lavage (BAL) fluid and plasma
      samples were collected from patients with ALI (n=30) and healthy controls (n=18,
      plasma; n=14, BAL fluid). Lung tissue was harvested from a separate group of
      patients and controls (n=10). Thioredoxin was measured by ELISA in fluids and by
      immunohistochemistry in tissue. Interleukin (IL)-8 levels were determined by
      ELISA. Disease severity was assessed as APACHE II and SOFA scores. RESULTS: BAL
      fluid levels of thioredoxin were higher in patients with ALI than in controls
      (median 61.6 ng/ml (IQR 34.9-132.9) v 16.0 ng/ml (IQR 8.9-25.1), p<0.0001);
      plasma levels were also significantly higher. When compared with controls,
      sections of wax embedded lung tissue from patients with ALI showed greater
      positive staining for thioredoxin in alveolar macrophages and type II epithelial
      cells. BAL fluid levels of thioredoxin correlated with IL-8 levels in BAL fluid
      but not with severity of illness scores or mortality. BAL fluid levels of
      thioredoxin, IL-8, and neutrophils were significantly greater in patients with
      ALI of pulmonary origin. CONCLUSIONS: Extracellular thioredoxin levels are raised
      in patients with ALI, particularly of pulmonary origin, and have a significant
      positive association with IL-8. Extracellular thioredoxin levels could provide a
      useful indication of inflammation in ALI.

PMID- 16601095
TI  - Losartan attenuates bleomycin induced lung fibrosis by increasing prostaglandin
      E2 synthesis.
AB  - BACKGROUND: The angiotensin system has a role in the pathogenesis of pulmonary
      fibrosis. This study examines the antifibrotic effect of losartan, an angiotensin
      II type 1 receptor antagonist, in bleomycin induced lung fibrosis and its
      possible implication in the regulation of prostaglandin E(2) (PGE(2)) synthesis
      and cyclooxygenase-2 (COX-2) expression. METHODS: Rats were given a single
      intratracheal instillation of bleomycin (2.5 U/kg). Losartan (50 mg/kg/day) was
      administrated orally starting one day before induction of lung fibrosis and
      continuing to the conclusion of each experiment. RESULTS: Losartan reduced the
      inflammation induced by bleomycin, as indicated by lower myeloperoxidase activity
      and protein content in the bronchoalveolar lavage fluid. Collagen deposition
      induced by bleomycin was inhibited by losartan, as shown by a reduction in the
      hydroxyproline content and the amelioration of morphological changes. PGE(2)
      levels were lower in fibrotic lungs than in normal lungs. Losartan significantly
      increased PGE(2) levels at both 3 and 15 days. A reduction in COX-2 expression by
      bleomycin was seen at 3 days which was relieved by losartan. CONCLUSIONS: The
      antifibrotic effect of losartan appears to be mediated by its ability to
      stimulate the production of PGE(2). Losartan, which is already widely used
      clinically, could be assessed as a new treatment in lung fibrosis.

PMID- 16601096
TI  - Vta1p and Vps46p regulate the membrane association and ATPase activity of Vps4p
      at the yeast multivesicular body.
AB  - Previous two-hybrid analysis of the 17 soluble class E Vps yeast proteins
      revealed that Vps46p/Did2p interacts with Vta1p and the AAA (ATPase associated
      with a variety of cellular activities) ATPase Vps4p. Here we report that the
      binding of Vps46p to Vps4p and Vta1p is direct and not mediated by additional
      proteins, and the binding of Vps46p to Vps4p is ATP independent. Vps46p regulates
      the membrane association of Vps4p and is required for the interaction of Vta1p
      with Vps32p/Snf7p of the ESCRT-III complex. Vta1p is a potent activator of Vps4p,
      stimulating the ATPase activity by 6- to 8-fold. These results reveal functional
      roles for the Vps46p and Vta1p proteins in regulating the ESCRT complex
      assembly/disassembly cycle in protein sorting at the yeast late endosome.

PMID- 16601097
TI  - Sparse time-frequency representations.
AB  - Auditory neurons preserve exquisite temporal information about sound features,
      but we do not know how the brain uses this information to process the rapidly
      changing sounds of the natural world. Simple arguments for effective use of
      temporal information led us to consider the reassignment class of time-frequency
      representations as a model of auditory processing. Reassigned time-frequency
      representations can track isolated simple signals with accuracy unlimited by the
      time-frequency uncertainty principle, but lack of a general theory has hampered
      their application to complex sounds. We describe the reassigned representations
      for white noise and show that even spectrally dense signals produce sparse
      reassignments: the representation collapses onto a thin set of lines arranged in
      a froth-like pattern. Preserving phase information allows reconstruction of the
      original signal. We define a notion of "consensus," based on stability of
      reassignment to time-scale changes, which produces sharp spectral estimates for a
      wide class of complex mixed signals. As the only currently known class of time
      frequency representations that is always "in focus" this methodology has general
      utility in signal analysis. It may also help explain the remarkable acuity of
      auditory perception. Many details of complex sounds that are virtually
      undetectable in standard sonograms are readily perceptible and visible in
      reassignment.

PMID- 16601098
TI  - Chaperone-mediated assembly of centromeric chromatin in vitro.
AB  - Every eukaryotic chromosome requires a centromere for attachment to spindle
      microtubules for chromosome segregation. Although centromeric DNA sequences vary
      greatly among species, centromeres are universally marked by the presence of a
      centromeric histone variant, centromeric histone 3 (CenH3), which replaces
      canonical histone H3 in centromeric nucleosomes. Conventional chromatin is
      maintained in part by histone chaperone complexes, which deposit the S phase
      limited (H3) and constitutive (H3.3) forms of histone 3. However, the mechanism
      that deposits CenH3 specifically at centromeres and faithfully maintains its
      chromosome location through mitosis and meiosis is unknown. To address this
      problem, we have biochemically purified a soluble assembly complex that targets
      tagged CenH3 to centromeres in Drosophila cells. Two different affinity
      procedures led to purification of the same complex, which consists of CenH3,
      histone H4, and a single protein chaperone, RbAp48, a highly abundant component
      of various chromatin assembly, remodeling, and modification complexes. The
      corresponding CenH3 assembly complex reconstituted in vitro is sufficient for
      chromatin assembly activity, without requiring additional components. The simple
      CenH3 assembly complex is in contrast to the multisubunit complexes previously
      described for H3 and H3.3, suggesting that centromeres are maintained by a
      passive mechanism that involves exclusion of the complexes that deposit canonical
      H3s during replication and transcription.

PMID- 16601099
TI  - Transmissibility of cholera: in vivo-formed biofilms and their relationship to
      infectivity and persistence in the environment.
AB  - The factors that enhance the waterborne spread of bacterial epidemics and sustain
      the epidemic strain in nature are unclear. Although the epidemic diarrheal
      disease cholera is known to be transmitted by water contaminated with pathogenic
      Vibrio cholerae, routine isolation of pathogenic strains from aquatic
      environments is challenging. Here, we show that conditionally viable
      environmental cells (CVEC) of pathogenic V. cholerae that resist cultivation by
      conventional techniques exist in surface water as aggregates (biofilms) of
      partially dormant cells. Such CVEC can be recovered as fully virulent bacteria by
      inoculating the water into rabbit intestines. Furthermore, when V. cholerae shed
      in stools of cholera patients are inoculated in environmental water samples in
      the laboratory, the cells exhibit characteristics similar to CVEC, suggesting
      that CVEC are the infectious form of V. cholerae in water and that CVEC in nature
      may have been derived from human cholera stools. We also observed that stools
      from cholera patients contain a heterogeneous mixture of biofilm-like aggregates
      and free-swimming planktonic cells of V. cholerae. Estimation of the relative
      infectivity of these different forms of V. cholerae cells suggested that the
      enhanced infectivity of V. cholerae shed in human stools is largely due to the
      presence of clumps of cells that disperse in vivo, providing a high dose of the
      pathogen. The results of this study support a model of cholera transmission in
      which in vivo-formed biofilms contribute to enhanced infectivity and
      environmental persistence of pathogenic V. cholerae.

PMID- 16601100
TI  - Antarctic birds breed later in response to climate change.
AB  - In the northern hemisphere, there is compelling evidence for climate-related
      advances of spring events, but no such long-term biological time series exist for
      the southern hemisphere. We have studied a unique data set of dates of first
      arrival and laying of first eggs over a 55-year period for the entire community
      of Antarctic seabirds in East Antarctica. The records over this long period show
      a general unexpected tendency toward later arrival and laying, an inverse trend
      to those observed in the northern hemisphere. Overall, species now arrive at
      their colonies 9.1 days later, on average, and lay eggs an average of 2.1 days
      later than in the early 1950s. Furthermore, these delays are linked to a decrease
      in sea ice extent that has occurred in eastern Antarctica, which underlies the
      contrasted effects of global climate change on species in Antarctica.

PMID- 16601101
TI  - Finite simple groups as expanders.
AB  - We prove that there exist k in and 0 < epsilon in such that every non-abelian
      finite simple group G, which is not a Suzuki group, has a set of k generators for
      which the Cayley graph Cay(G; S) is an epsilon-expander.

PMID- 16601102
TI  - Phosphorylation and activation of PINOID by the phospholipid signaling kinase 3
      phosphoinositide-dependent protein kinase 1 (PDK1) in Arabidopsis.
AB  - Activity of the serine-threonine protein kinase PINOID (PID) has been implicated
      in the asymmetrical localization of the membrane-associated PINFORMED (PIN)
      family of auxin transport facilitators. However, the means by which PID regulates
      PIN protein distribution is unknown. We have used recombinant PID protein to
      dissect the regulation of PID activity in vitro. We demonstrate that
      intramolecular PID autophosphorylation is required for the ability of PID to
      phosphorylate an exogenous substrate. PID-like mammalian AGC kinases act in a
      phosphorylation cascade initiated by the phospholipid-associated kinase, 3
      phosphoinositide-dependent protein kinase 1 (PDK1), which binds to the C-terminal
      hydrophobic PDK1-interacting fragment (PIF) domain found in PDK1 substrates. We
      find that Arabidopsis PDK1 interacts with PID, and that transphosphorylation by
      PDK1 increases PID autophosphorylation. We show that a PID activation loop serine
      is required for PDK1-dependent PID phosphorylation. This activation is rapid and
      requires the PIF domain. Cell extracts from flowers and seedling shoots
      dramatically increase PID phosphorylation in a tissue-specific manner. A PID
      protein variant in which the PIF domain was mutated failed to be activated by the
      seedling shoot extracts. PID immunoprecipitated from Arabidopsis cells in which
      PDK1 expression was inhibited by RNAi showed a dramatic reduction in
      transphosphorylation of myelin basic protein substrate. These results indicate
      that AtPDK1 is a potent enhancer of PID activity and provide evidence that
      phospholipid signaling may play a role in the signaling processes controlling
      polar auxin transport.

PMID- 16601103
TI  - Interference between independent fluctuating condensates.
AB  - We consider a problem of interference between two independent condensates that
      lack true long-range order. We show that their interference pattern contains
      information about correlation functions within each condensate. As an example, we
      analyze the interference between a pair of one-dimensional interacting Bose
      liquids. We find universal scaling of the average fringe contrast with system
      size and temperature that depends only on the Luttinger parameter. Moreover, the
      full distribution of the fringe contrast, which is also equivalent to the full
      counting statistics of the interfering atoms, changes with interaction strength
      and lends information on high-order correlation functions. We also demonstrate
      that the interference between two-dimensional condensates at finite temperature
      can be used as a direct probe of the Kosterlitz-Thouless transition. Finally, we
      discuss the generalization of our results to describe the interference of a
      periodic array of independent fluctuating condensates.

PMID- 16601105
TI  - Can secondary school students' self-reported measures of height and weight be
      trusted? An effect size approach.
AB  - BACKGROUND: Self-reported measures of height and weight are a cost-effective
      alternative to direct measures in large-scale studies. This study was designed to
      examine the accuracy of adolescent students' self-reported height and weight
      taking into consideration the magnitude of the differences. METHODS: Self
      reported height and weight were taken from 300 secondary public schools students.
      Participants' actual height and weight were subsequently verified. Body mass
      index (BMI; kg/m2) was calculated separately from reported and from actual
      measures. Adolescents' whose measured BMI was above the 85th percentile were
      characterized as 'at risk for overweight/obese'. RESULTS: There was no gender
      effect on the discrepancy between reported and actual measures. Overall
      adolescents significantly underestimated their weight and BMI. Although
      correlation coefficients were high, eta-square (eta2) values indicate large bias
      for weight (0.36) and BMI (0.31). 'At risk for overweight/obese' individuals
      underestimated their weight and BMI to a greater extent than their 'normal
      weight' counterparts. CONCLUSIONS: The magnitude of the discrepancies call into
      question the accuracy of self-reported weight and consequently the estimated BMI.
      Correlation coefficients did not provide any valuable information about the
      discrepancy between the self-reported and actual measures. A better understanding
      of the validity of self-reported height and weight could be reached if
      interpretation of the results is based on both statistical significance and
      magnitude of the differences.

PMID- 16601104
TI  - Nicotine inhibits apoptosis induced by chemotherapeutic drugs by up-regulating
      XIAP and survivin.
AB  - Non-small cell lung cancer (NSCLC) demonstrates a strong etiologic association
      with smoking. Although nicotine is not carcinogenic, it can induce cell
      proliferation and angiogenesis and suppress apoptosis induced by certain agents.
      Here we show that nicotine inhibits apoptosis induced by the drugs gemcitabine,
      cisplatin, and taxol, which are used to treat NSCLCs. This protection correlated
      with the induction of XIAP and survivin by nicotine in a panel of human NSCLC
      cell lines, and depletion of XIAP and survivin ablated the protective effects of
      nicotine. The antiapoptotic effects of nicotine were mediated by dihydro beta
      erythroidine-sensitive alpha3-containing nicotinic acetylcholine receptors and
      required the Akt pathway. Chromatin immunoprecipitation assays demonstrated that
      nicotine stimulation caused an increased recruitment of E2F1 and concomitant
      dissociation of retinoblastoma tumor suppressor protein (Rb) from survivin
      promoter in A549 cells. Moreover, ablation of E2F1 levels caused abrogation of
      the protective effects of nicotine against cisplatin-induced apoptosis in A549
      cells whereas ablation of signal transducer and activator of transcription 3
      levels had no effect. These studies suggest that exposure to nicotine might
      negatively impact the apoptotic potential of chemotherapeutic drugs and that
      survivin and XIAP play a key role in the antiapoptotic activity of nicotine.

PMID- 16601106
TI  - When are health inequalities a political problem?
AB  - Is it possible to define criteria by which a political decision on which
      inequities in health should be addressed can be made? It has been suggested that
      differences which are unnecessary and avoidable and those which are unfair and
      unjust are inequalities which should lead to political action. In the article it
      is argued that it is not possible to make a clear distinction between avoidable
      and unavoidable differences, and that the extent to which differences are
      considered unfair depends on political and normative standpoints, and generally
      acceptable criteria can therefore not be established.

PMID- 16601107
TI  - Public health in the Balkan region: one school's experience.

PMID- 16601108
TI  - The effect of the national demonstration project Healthy Respect on teenage
      sexual health behaviour.
AB  - BACKGROUND: As part of the independent evaluation of Healthy Respect (a national
      demonstration project to improve teenage sexual health in Scotland) this study
      examined the effect of the school-based sexual health education intervention
      comprising multiprofessional classroom delivery and alongside drop-in clinics on
      teenage sexual behaviour outcomes. METHODS: Before-and-after cross-sectional
      surveys of secondary school pupils (average age 14 years and 6 months) were used
      in 10 Healthy Respect intervention schools in Lothian region and 5 comparison
      schools without intervention in Grampian region (2001 and 2003). RESULTS: By
      2003, the proportion of pupils in Lothian feeling confident about getting condoms
      and using condoms properly significantly increased, more Lothian pupils
      (particularly boys) showed improved knowledge about condoms being protective
      against sexually transmitted infections. No further evidence of improved
      knowledge, attitudes, or intentions was evident after the intervention. Pupils in
      Lothian remained more likely to think using a condom would be embarrassing
      (especially girls), would reduce sexual enjoyment (especially boys), and
      intentions about condom use (as closer predictors of actual behaviour change)
      showed no significant improvement. More Lothian ( approximately 24%) than
      Grampian ( approximately 19%) pupils report having had sexual intercourse at age
      <16 years, both before and after the intervention, with no evidence of a
      significant reduction in Lothian by 2003. Overall differences in attitudes to
      condom use by gender were noted. Findings remain consistent in both unadjusted
      and adjusted comparisons. CONCLUSION: These findings demonstrate limited impact
      on sexual health behaviour outcomes, and raise questions about the likely and
      achievable sexual health gains for teenagers from school-based interventions.

PMID- 16601109
TI  - Movie moguls: British American Tobacco's covert strategy to promote cigarettes in
      Eastern Europe.
AB  - BACKGROUND: Though the cigarette companies have long publicly denied paying for
      product placement in films, the documentary evidence from the 1950s-1980s
      overwhelmingly suggests otherwise. METHODS: Approximately 800,000 pages of
      previously secret internal corporate British American Tobacco Company documents
      were reviewed at the Minnesota Tobacco Document Depository from March 2003
      through May 2005. Documents were also searched online at the various tobacco
      document collections between February 2004 and November 2004. RESULTS: A small
      collection of internal corporate documents from British American Tobacco show
      that in the late 1990s the company evaluated investing in a movie destined for
      Eastern Europe. By being an investor, BAT could influence the alteration of the
      movie script to promote BAT's brands, thus providing marketing opportunities
      without a clear violation of movie product placement restrictions. CONCLUSION:
      Future protocols to the WHO Framework Convention on Tobacco Control should seek
      to curtail more than just payment for tobacco product placement. More restrictive
      provisions will be needed to hinder creative strategies by the tobacco industry
      to continue tobacco promotion and trademark diversification through movies.

PMID- 16601110
TI  - Gender differences in role of alcohol in fatal injury events.
AB  - BACKGROUND: The aim was to investigate the differences in alcohol involvement in
      fatal injury events between females and males. METHODS: Information was obtained
      from the Forensic Medicine Database and the Forensic Toxicology Database of the
      National Board of Forensic Medicine, and from the inpatient register of the
      National Board of Health and Welfare. Alcohol was regarded to be involved in the
      injury event: if there was any indication that the deceased was a 'known
      alcoholic'; if the underlying or contributing causes of death were alcohol
      related; if the deceased had alcohol-related inpatient diagnosis during a 3-year
      period prior to death; or if the deceased tested positive for blood alcohol at
      autopsy. All injured cases who underwent medico-legal autopsies (1992-1996) in
      Sweden were analysed (4471 females and 11 156 males). RESULTS: Compared to males,
      females died more often (P < 0.05) in intentional injury events (48.0% females,
      44.2% males), were less often (P < 0.001) blood alcohol-positive (29% females,
      43% males), had lower (P < 0.05) blood alcohol concentrations (0.17% in females,
      0.18% in males), and were less likely (P < 0.001) to have an alcohol-related
      history (18.4% females, 24.4% males). For females, intentional deaths (31.4%)
      were significantly (P < 0.001) more often alcohol-related than unintentional
      deaths (22.9%). A significantly (P < 0.001) higher proportion of deaths in males
      (48.4%) were alcohol-related compared to females (32.9%). CONCLUSIONS: Almost
      every third injury event in females and in almost every other event in males is
      alcohol-related, showing that alcohol plays an important part in fatal injuries
      in females even though it is mostly a male problem.

PMID- 16601111
TI  - Building public health associations in the transition countries of south-eastern
      Europe: the example of Albania.
AB  - The Albanian Forum of Public Health (AFPH), an umbrella organization including
      different public health associations operating in Albania, was established in
      March 2004 with the support of the European Public Health Association (EUPHA) and
      the Open Society Institute (OSI). Ever since its establishment the AFPH has been
      an open arena wherein opinions and options for rational health policies
      comprising all relevant issues of the New Public Health are discussed,
      formulated, and documented near the Albanian Ministry of Health. Notwithstanding
      the laudable mission of the AFPH, there is an emerging need to establish a
      regional Public Health Forum in south-east Europe as a basic prerequisite for
      sustainable development of public health in these countries. Most conveniently,
      this regional umbrella organization should have a supporting Secretariat based in
      one of the south-east European countries. Nevertheless, there is a clear call for
      international funding with participation of different agencies and bodies (OSI,
      EUPHA, Canadian International Development Agency, and the Stability Pact). A
      regional association in the south-east Europe would enable the organization of
      annual conferences in the most renowned institutions in the region. Also, a
      regional collaboration among public health associations would be a suitable start
      for the development of research in south-east Europe. Furthermore, the existence
      of a regional public health association would make feasible the establishment of
      a scientific public health journal for south-east Europe in the English language.

PMID- 16601112
TI  - Official marital status, cohabiting, and self-rated health-time trends in
      Finland, 1978-2001.
AB  - BACKGROUND: Married persons are healthier and live longer than single, divorced,
      and widowed persons. Time trends in self-rated health (SRH) by marital status and
      cohabitation have remained largely unstudied. We aim to assess the levels and
      trends of SRH by official marital status and cohabitation, and to study the
      causes of these differences. METHODS: Two nationally representative cross
      sectional surveys were conducted 20 years apart in Finland. Data on self-reported
      marital status, SRH, education, smoking, and long-standing illness were collected
      from Finns aged 30-64 years in 1978-80 (Mini-Finland Health Survey, N = 6102,
      response rate 96%) and 2000-01 (Health 2000 Survey, N = 5871, response rate 92%).
      RESULTS: SRH has improved in the last 20 years, but differences between marital
      status groups have not reduced. In 2000-01, non-married persons reported worse
      SRH than married persons. Among men, single [cumulative odds ratio (COR) = 1.55;
      95% confidence interval (95% CI) 1.22-1.99] and divorced (COR = 1.55; 95% CI 1.17
      2.05) persons showed the poorest SRH, while among women widows (1.53; 95% CI 1.04
      2.26) were the most disadvantaged group. The SRH of cohabiting persons did not
      significantly differ from that of married persons. Differences in educational
      structure, smoking, and the prevalence of long-term illness explain part of the
      marital status differences in SRH among men, but less so among women. Among both
      single men and women as well as among widowed women, SRH had improved slightly
      less than in the other groups. CONCLUSION: The challenges on public health posed
      by growing numbers of currently not married people are likely to increase.

PMID- 16601113
TI  - Novel anti-inflammatory role for glycogen synthase kinase-3beta in the inhibition
      of tumor necrosis factor-alpha- and interleukin-1beta-induced inflammatory gene
      expression.
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is a serine/threonine kinase with a
      broad array of cellular targets, such as cytoskeletal proteins and transcription
      factors. Recent studies with GSK-3beta-null mice showed impaired NFkappaB
      mediated survival responses. Because NFkappaB serves a dual role as a key
      regulator of cytokine-induced inflammatory gene expression and apoptosis, we
      investigated whether modulation of GSK-3beta expression affects cytokine-induced
      and NFkappaB-mediated inflammatory gene expression. We observed that tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) treatment of
      primary cultures of human microvascular cells reduced net endogenous active GSK
      3beta protein levels while inducing inflammatory cytokine (IL-6 and monocyte
      chemoattractant protein-1 (MCP-1)) expression. Interestingly, inhibition of GSK
      3beta by antisense oligonucleotides or pharmacological agent (10 mm lithium)
      potentiated TNF-induced expression of IL-6 and MCP-1 by 2-6-fold suggesting that
      inhibition of GSK-3beta under inflammatory conditions (exposure to TNF-alpha and
      IL-1beta) may contribute to enhanced cytokine expression. Overexpression of GSK
      3beta in endothelial cells, in contrast, significantly inhibited (by 70%, p <
      0.01) both TNF-alpha and IL-1beta-induced expression of IL-6, MCP-1, and vascular
      cell adhesion molecule-1. Using adenoviruses in lipopolysaccharide-stimulated
      mice, overexpression of GSK-3beta significantly decreased TNF-alpha expression in
      lung and heart tissues (38 and 15%, respectively), further confirming the anti
      inflammatory role of GSK-3beta. Overexpression of GSK-3beta did not affect the
      TNF-alpha-induced nuclear translocation of NFkappaB but reduced the nuclear half
      life of TNF-alpha-induced NFkappaB considerably (by as much as 9 h) and enhanced
      phosphorylation (by as much as 33%). Interestingly, neither endothelial cell
      survival nor NFkappaB-mediated expression of anti-apoptotic genes was affected by
      GSK-3beta overexpression. We conclude that GSK-3beta selectively regulates
      NFkappaB-mediated inflammatory gene expression by controlling the flow of
      NFkappaB activity between transcription of inflammatory and survival genes.

PMID- 16601114
TI  - Phosphatidylinositol 5-kinase stimulates apical biosynthetic delivery via an
      Arp2/3-dependent mechanism.
AB  - The mechanisms by which polarized epithelial cells target distinct carriers
      enriched in newly synthesized proteins to the apical or basolateral membrane
      remain largely unknown. Here we investigated the effect of phosphatidylinositol
      metabolism and modulation of the actin cytoskeleton, two regulatory mechanisms
      that have individually been suggested to function in biosynthetic traffic, on
      polarized traffic in Madin-Darby canine kidney cells. Overexpression of
      phosphatidylinositol 5-kinase (PI5K) increased actin comet frequency in Madin
      Darby canine kidney cells and concomitantly stimulated trans-Golgi network (TGN)
      to apical membrane delivery of the raft-associated protein influenza
      hemagglutinin (HA), but did not affect delivery of a non-raft-associated apical
      protein or a basolateral marker. Modulation of actin comet formation by
      pharmacologic means, by overexpression of the TGN-localized inositol
      polyphosphate 5-phosphatase Ocrl, or by blockade of Arp2/3 function had parallel
      effects on the rate of apical delivery of HA. Moreover, HA released from a TGN
      block was colocalized in transport carriers in association with PI5K and actin
      comets. Inhibition of Arp2/3 function in combination with microtubule
      depolymerization led to a virtual block in HA delivery, suggesting synergistic
      coordination of these cytoskeletal assemblies in membrane transport. Our results
      suggest a previously unidentified role for actin comet-mediated propulsion in the
      biosynthetic delivery of a subset of apical proteins.

PMID- 16601115
TI  - Structural basis of reduction-dependent activation of human cystatin F.
AB  - Cystatins are important natural cysteine protease inhibitors targeting primarily
      papain-like cysteine proteases, including cathepsins and parasitic proteases like
      cruzipain, but also mammalian asparaginyl endopeptidase. Mammalian cystatin F,
      which is expressed almost exclusively in hematopoietic cells and accumulates in
      lysosome-like organelles, has been implicated in the regulation of antigen
      presentation and other immune processes. It is an unusual cystatin superfamily
      member with a redox-regulated activation mechanism and a restricted specificity
      profile. We describe the 2.1A crystal structure of human cystatin F in its
      dimeric "off" state. The two monomers interact in a fashion not seen before for
      cystatins or cystatin-like proteins that is crucially dependent on an unusual
      intermolecular disulfide bridge, suggesting how reduction leads to monomer
      formation and activation. Strikingly, core sugars for one of the two N-linked
      glycosylation sites of cystatin F are well ordered, and their conformation and
      interactions with the protein indicate that this unique feature of cystatin F may
      modulate its inhibitory properties, in particular its reduced affinity toward
      asparaginyl endopeptidase compared with other cystatins.

PMID- 16601117
TI  - SecA supports a constant rate of preprotein translocation.
AB  - In Escherichia coli, secretory proteins (preproteins) are translocated across the
      cytoplasmic membrane by the Sec system composed of a protein-conducting channel,
      SecYEG, and an ATP-dependent motor protein, SecA. After binding of the preprotein
      to SecYEG-bound SecA, cycles of ATP binding and hydrolysis by SecA are thought to
      drive the stepwise translocation of the preprotein across the membrane. To
      address how the length of a preprotein substrate affects the SecA-driven
      translocation process, we constructed derivatives of the precursor of the outer
      membrane protein A (proOmpA) with 2, 4, 6, and 8 in-tandem repeats of the
      periplasmic domain. With increasing polypeptide length, an increasing delay in
      the time before full-length translocation was observed, but the translocation
      rate expressed as amino acid translocation per minute remained constant. These
      data indicate that in the ATP-dependent reaction, SecA drives a constant rate of
      preprotein translocation consistent with a stepping mechanism of translocation.

PMID- 16601116
TI  - Identification of a pH sensor in the furin propeptide that regulates enzyme
      activation.
AB  - The folding and activation of furin occur through two pH- and compartment
      specific autoproteolytic steps. In the endoplasmic reticulum (ER), profurin folds
      under the guidance of its prodomain and undergoes an autoproteolytic excision at
      the consensus furin site Arg-Thr-Lys-Arg107/ generating an enzymatically masked
      furin-propeptide complex competent for transport to late secretory compartments.
      In the mildly acidic environment of the trans-Golgi network/endosomal system, the
      bound propeptide is cleaved at the internal site 69HRGVTKR75/, unmasking active
      furin capable of cleaving substrates in trans. Here, by using cellular,
      biochemical, and modeling studies, we demonstrate that the conserved His69 is a
      pH sensor that regulates the compartment-specific cleavages of the propeptide. In
      the ER, unprotonated His69 stabilizes a solvent-accessible hydrophobic pocket
      necessary for autoproteolytic excision at Arg107. Profurin molecules unable to
      form the hydrophobic pocket, and hence, the furin-propeptide complex, are
      restricted to the ER by a PACS-2- and COPI-dependent mechanism. Once exposed to
      the acidic pH of the late secretory pathway, protonated His69 disrupts the
      hydrophobic pocket, resulting in exposure and cleavage of the internal cleavage
      site at Arg75 to unmask the enzyme. Together, our data explain the pH-regulated
      activation of furin and how this His-dependent regulatory mechanism is a model
      for other proteins.

PMID- 16601118
TI  - Heteromeric, but not homomeric, connexin channels are selectively permeable to
      inositol phosphates.
AB  - Previous work has shown that channels formed by both connexin (Cx)26 and Cx32
      (heteromeric Cx26/Cx32 hemichannels) are selectively permeable to cAMP and cGMP.
      To further investigate differential connexin channel permeability among second
      messengers, and the influence of connexin channel composition on the selectivity,
      the permeability of inositol phosphates with one to four phosphate groups through
      homomeric Cx26, homomeric Cx32, and heteromeric Cx26/Cx32 channels was examined.
      Connexin channels were purified from transfected HeLa cells and from rat, mouse,
      and guinea pig livers, resulting in channels with a broad range of Cx26/Cx32
      aggregate ratios. Permeability to inositol phosphates was assessed by flux
      through reconstituted channels. Surprisingly, myoinositol and all inositol
      phosphates tested were permeable through homomeric Cx32 and homomeric Cx26
      channels. Even more surprising, heteromeric Cx26/Cx32 channels showed striking
      differences in permeability among inositol phosphates with three or four
      phosphate groups and among isomers of inositol triphosphate. Thus, heteromeric
      channels are selectively permeable among inositol phosphates, whereas the
      corresponding homomeric channels are not. There was no discernible difference in
      the permeability of channels with similar Cx26/Cx32 ratios purified from native
      and heterologous sources. The molecular selectivity of heteromeric channels among
      three inositol triphosphates could not be accounted for by simple connexin
      isoform stoichiometry distributions and therefore may depend on specific isoform
      radial arrangements within the hexameric channels. Dynamic regulation of channel
      composition in vivo may effectively and efficiently modulate intercellular
      signaling by inositol phosphates.

PMID- 16601119
TI  - Collagen plays an active role in the aggregation of beta2-microglobulin under
      physiopathological conditions of dialysis-related amyloidosis.
AB  - Dialysis-related amyloidosis is characterized by the deposition of insoluble
      fibrils of beta(2)-microglobulin (beta(2)-m) in the musculoskeletal system.
      Atomic force microscopy inspection of ex vivo amyloid material reveals the
      presence of bundles of fibrils often associated to collagen fibrils. Aggregation
      experiments were undertaken in vitro with the aim of reproducing the
      physiopathological fibrillation process. To this purpose, atomic force
      microscopy, fluorescence techniques, and NMR were employed. We found that in
      temperature and pH conditions similar to those occurring in periarticular tissues
      in the presence of flogistic processes, beta(2)-m fibrillogenesis takes place in
      the presence of fibrillar collagen, whereas no fibrils are obtained without
      collagen. Moreover, the morphology of beta(2)-m fibrils obtained in vitro in the
      presence of collagen is extremely similar to that observed in the ex vivo sample.
      This result indicates that collagen plays a crucial role in beta(2)-m amyloid
      deposition under physiopathological conditions and suggests an explanation for
      the strict specificity of dialysis-related amyloidosis for the tissues of the
      skeletal system. We hypothesize that positively charged regions along the
      collagen fiber could play a direct role in beta(2)-m fibrillogenesis. This
      hypothesis is sustained by aggregation experiments performed by replacing
      collagen with a poly-L-lysine-coated mica surface. As shown by NMR measurements,
      no similar process occurs when poly-L-lysine is dissolved in solution with
      beta(2)-m. Overall, the findings are consistent with the estimates resulting from
      a simplified collagen model whereby electrostatic effects can lead to high local
      concentrations of oppositely charged species, such as beta(2)-m, that decay on
      moving away from the fiber surface.

PMID- 16601120
TI  - Dimeric Dnm1-G385D interacts with Mdv1 on mitochondria and can be stimulated to
      assemble into fission complexes containing Mdv1 and Fis1.
AB  - Interactions between yeast Dnm1p, Mdv1p, and Fis1p are required to form fission
      complexes that catalyze division of the mitochondrial compartment. During the
      formation of mitochondrial fission complexes, the Dnm1p GTPase self-assembles
      into large multimeric complexes on the outer mitochondrial membrane that are
      visualized as punctate structures by fluorescent labeling. Although it is clear
      that Fis1p.Mdv1p complexes on mitochondria are required for the initial
      recruitment of Dnm1p, it is not clear whether Dnm1p puncta assemble before or
      after this recruitment step. Here we show that the minimum oligomeric form of
      cytoplasmic Dnm1p is a dimer. The middle domain mutant protein Dnm1G385Dp forms
      dimers in vivo but fails to assemble into punctate structures. However, this
      dimeric mutant stably interacts with Mdv1p on the outer mitochondrial membrane,
      demonstrating that assembly of stable Dnm1p multimers is not required for Dnm1p
      Mdv1p association or for mitochondrial recruitment of Dnm1p. Dnm1G385Dp is
      reported to be a terminal dimer in vitro. We describe conditions that allow
      assembly of Dnm1G385Dp into functional fission complexes on mitochondria in vivo.
      Using these conditions, we demonstrate that multimerization of Dnm1p is required
      to promote reorganization of Mdv1p from a uniform mitochondrial localization into
      punctate fission complexes. Our studies also reveal that Fis1p is present in
      these assembled fission complexes. Based on our results, we propose that Dnm1p
      dimers are initially recruited to the membrane via interaction with Mdv1p.Fis1p
      complexes. These dimers then assemble into multimers that subsequently promote
      the reorganization of Mdv1p into punctate fission complexes.

PMID- 16601122
TI  - Evidence that fibulin family members contribute to the steroid-dependent
      extravascular sequestration of sex hormone-binding globulin.
AB  - Sex hormone-binding globulin (SHBG) binds steroids in the blood but is also
      present in the extravascular compartments of some tissues. Mice expressing a
      human SHBG transgene in the liver have human SHBG in their blood. In these
      animals, human SHBG accumulates within the stromal matrix of the endometrium and
      epididymis. This is remarkable because these tissues do not express the
      transgene. Human SHBG administered intravenously to wild-type mice in the
      presence of estradiol is rapidly sequestered within the endometrial stroma, and
      this prompted us to search for SHBG interacting proteins. Yeast two-hybrid
      screens revealed that fibulin-1D and fibulin-2 interact with the amino-terminal
      laminin G domain of SHBG. These interactions were verified in GST-pull down
      assays in which human SHBG bound the carboxyl-terminal domains of fibulin-1D and
      fibulin-2 in a steroid-dependent manner, with estradiol being the most effective
      ligand, and were enhanced by reducing the N-glycosylation of human SHBG. Like
      human SHBG, fibulin-1 and fibulin-2 concentrate within the endometrial stroma. In
      addition, SHBG co-immunoprecipitates with these fibulins in a proestrus uterine
      extract. These matrix-associated proteins may therefore sequester plasma SHBG
      within uterine stroma where it can control sex-steroid access to target cells.
      Given the interplay between fibulins and numerous proteins within the basal
      lamina, interactions between SHBG and matrix proteins may exert novel biological
      effects.

PMID- 16601121
TI  - Regulation of albumin endocytosis by PSD95/Dlg/ZO-1 (PDZ) scaffolds. Interaction
      of Na+-H+ exchange regulatory factor-2 with ClC-5.
AB  - The constitutive reuptake of albumin from the glomerular filtrate by receptor
      mediated endocytosis is a key function of the renal proximal tubules. Both the Cl
      channel ClC-5 and the Na+-H+ exchanger isoform 3 are critical components of the
      macromolecular endocytic complex that is required for albumin uptake, and
      therefore the cell-surface levels of these proteins may limit albumin
      endocytosis. This study was undertaken to investigate the potential roles of the
      epithelial PDZ scaffolds, Na+-H+ exchange regulatory factors, NHERF1 and NHERF2,
      in albumin uptake by opossum kidney (OK) cells. We found that ClC-5 co
      immunoprecipitates with NHERF2 but not NHERF1 from OK cell lysate. Experiments
      using fusion proteins demonstrated that this was a direct interaction between an
      internal binding site in the C terminus of ClC-5 and the PDZ2 module of NHERF2.
      In OK cells, NHERF2 is restricted to the intravillar region while NHERF1 is
      located in the microvilli. Silencing NHERF2 reduced both cell-surface levels of
      ClC-5 and albumin uptake. Conversely, silencing NHERF1 increased cell-surface
      levels of ClC-5 and albumin uptake, presumably by increasing the mobility of NHE3
      in the membrane and its availability to the albumin uptake complex. Surface
      biotinylation experiments revealed that both NHERF1 and NHERF2 were associated
      with the plasma membrane and that NHERF2 was recruited to the membrane in the
      presence of albumin. The importance of the interaction between NHERF2 and the
      cytoskeleton was demonstrated by a significant reduction in albumin uptake in
      cells overexpressing an ezrin binding-deficient mutant of NHERF2. Thus NHERF1 and
      NHERF2 differentially regulate albumin uptake by mechanisms that ultimately alter
      the cell-surface levels of ClC-5.

PMID- 16601123
TI  - SmpB triggers GTP hydrolysis of elongation factor Tu on ribosomes by compensating
      for the lack of codon-anticodon interaction during trans-translation initiation.
AB  - Bacterial tmRNA rescues ribosomes that stall because of defective mRNAs via the
      trans-translation process. Although entry of the charged transfer messenger RNA
      (tmRNA) into the ribosome proceeded in the absence of elongation factor (EF-Tu)
      and in the presence of EF-Tu and the antibiotic kirromycin, evidence was found
      for the involvement of EF-Tu in trans-translation initiation. The polyalanine
      synthesis system attained by using a tmRNA variant consisting of only the tRNA
      like domain revealed that it was completely dependent on the presence of SmpB and
      greatly enhanced by EF-Tu and EF-G. Actually, ribosome-dependent GTPase activity
      of EF-Tu was stimulated by the addition of SmpB and tmRNA but independently of
      template mRNA, demonstrating that SmpB compensates for the lack of codon
      anticodon interaction during the first step of the trans-translation initiation.
      Based on these results, we suggest that SmpB structurally mimics the anticodon
      arm of tRNA and elicits GTP hydrolysis of EF-Tu upon tmRNA accommodation in the A
      site of the ribosome.

PMID- 16601124
TI  - Activation of Tyk2 and Stat3 is required for the apoptotic actions of interferon
      beta in primary pro-B cells.
AB  - The growth-inhibitory effects of type 1 interferons (IFNs) (IFNalpha/beta) are
      complex, and the role of apoptosis in their antigrowth effects is variable and
      not well understood. We have examined primary murine interleukin-7-dependent bone
      marrow-derived pro-B cells, where IFNbeta, but not IFNalpha, induces programmed
      cell death (PCD). IFNbeta-stimulated apoptosis is the same in pro-B cells derived
      from wild type and Stat1(-/-) mice. However, in pro-B cells from Tyk2(-/-) mice,
      where there is normal activation of Stat1 and Stat2, IFNbeta-stimulated PCD is
      not observed. Loss of B cells in lymphocytic choriomeningitis virus-infected mice
      has been shown to be mediated through the expression of IFNalpha/beta (1). In
      wild type mice infected with lymphocytic choriomeningitis virus, there is a
      greater loss of B cells in the bone marrow and spleen than in Tyk2(-/-) mice
      infected with the virus, suggesting that the expression of this kinase plays an
      in vivo role in IFNalpha/beta-mediated PCD. In contrast to IFNbeta-stimulated
      tyrosine phosphorylation of Stat1 and Stat2, Stat3 tyrosine phosphorylation is
      defective in Tyk2(-/-) pro-B cells, suggesting that this Stat family member is
      required for apoptosis. In support of this hypothesis, inhibition of Stat3
      activation in wild type B cells reverses the apoptotic effects of IFNbeta.
      Furthermore, expression of a constitutively active form of Stat3 in Tyk2(-/-) B
      cells partially restores IFNbeta-stimulated PCD. These results demonstrate an
      important role of Tyk2-mediated tyrosine phosphorylation of Stat3 in the ability
      of IFNbeta to stimulate apoptosis of primary pro-B cells.

PMID- 16601125
TI  - Family 6 carbohydrate binding modules in beta-agarases display exquisite
      selectivity for the non-reducing termini of agarose chains.
AB  - Carbohydrate recognition is central to the biological and industrial exploitation
      of plant structural polysaccharides. These insoluble polymers are recalcitrant to
      microbial degradation, and enzymes that catalyze this process generally contain
      non-catalytic carbohydrate binding modules (CBMs) that potentiate activity by
      increasing substrate binding. Agarose, a repeat of the disaccharide 3,6-anhydro
      alpha-L-galactose-(1,3)-beta-D-galactopyranose-(1,4), is the dominant matrix
      polysaccharide in marine algae, yet the role of CBMs in the hydrolysis of this
      important polymer has not previously been explored. Here we show that family 6
      CBMs, present in two different beta-agarases, bind specifically to the non
      reducing end of agarose chains, recognizing only the first repeat of the
      disaccharide. The crystal structure of one of these modules Aga16B-CBM6-2, in
      complex with neoagarohexaose, reveals the mechanism by which the protein displays
      exquisite specificity, targeting the equatorial O4 and the axial O3 of the
      anhydro-L-galactose. Targeting of the CBM6 to the non-reducing end of agarose
      chains may direct the appended catalytic modules to areas of the plant cell wall
      attacked by beta-agarases where the matrix polysaccharide is likely to be more
      amenable to further enzymic hydrolysis.

PMID- 16601126
TI  - Progress report on the AJRCCM: continued growth and evolution for the journal.

PMID- 16601127
TI  - Heliox in chronic obstructive pulmonary disease: lightening the airflow.

PMID- 16601128
TI  - Update in sleep and control of ventilation 2005.

PMID- 16601129
TI  - Update in critical care 2005.

PMID- 16601130
TI  - Why is "hard" evidence "hard" to accept?

PMID- 16601131
TI  - Total educational debt may be more important than monthly debt payments on career
      choices.

PMID- 16601132
TI  - Association between adrenal insufficiency and ventilator weaning.

PMID- 16601133
TI  - Insulin-like peptide 5: expression in the mouse brain and mobilization of
      calcium.
AB  - Insulin-like peptide 5 (INSL5) mRNA was detected in the mouse hypothalamus by RT
      PCR. Immunohistochemical studies using an antiserum against the mouse INSL5
      peptide revealed INSL5-immunoreactive (irINSL5) neurons in the paraventricular,
      supraoptic, accessory secretory, and supraoptic retrochiasmatic nuclei and
      immunoreactive cell processes in the internal layer of the median eminence. In
      the pituitary, irINSL5 was detected in terminal-like elements of the posterior
      lobe and in cells of the anterior lobe. Double-labeling experiments showed that
      irINSL5 is expressed in vasopressin-, but not oxytocin-containing neurons. INSL5
      (100 nm) administered to dissociated and cultured mouse hypothalamic neurons
      elevated cytosolic calcium concentrations [Ca(2+)](i), as assessed by the
      microfluorimetric fura-2 method. In a Ca(2+)-free medium, INSL5 induced in
      dissociated neurons an increase of [Ca(2+)](i), which was sensitive to the
      endoplasmic reticulum calcium pump inhibitor thapsigargin (1 microm) and the
      IP(3) receptor blocker 2-aminoethoxydiphenyl borate (100 microm) or xestospongin
      C (5 microm). Our result provides the first evidence that INSL5 is expressed in a
      population of cells in the mouse hypothalamus and pituitary and that it elevates
      [Ca(2+)](i) by a mechanism involving both Ca(2+) influx and Ca(2+) release from
      intracellular stores. The concentration of irINSL5 in the hypothalamic-pituitary
      axis suggests a neuroendocrine function of this insulin superfamily member.

PMID- 16601134
TI  - Inhibins differentially antagonize activin and bone morphogenetic protein action
      in a mouse adrenocortical cell line.
AB  - Inhibin, a member of the TGF-beta superfamily, has been proposed to act as an
      inhibitor of activin and bone morphogenetic protein (BMP) by sequestering their
      type II receptors in nonsignaling complexes with betaglycan. This mechanism of
      inhibin action was tested in a mouse adrenocortical (AC) cell line by examining
      the effects of inhibins A and B on cytochrome P450 17alpha-hydroxylase 17,20
      lyase (Cyp17) expression and 17alpha-hydroxylase activity, measured by
      progesterone 17alpha-hydroxylation, in the absence and presence of activin or BMP
      isoforms. Cyp17 mRNA endogenously expressed by AC cells was suppressed by
      activins A and B and BMP-2, -6, and -7, and each ligand accordingly inhibited
      17alpha-hydroxyprogesterone production (IC(50) of 0.24, 0.27, 0.4, 0.51, and 2.2
      nm, respectively). Neither inhibin A nor inhibin B alone affected Cyp17
      expression or 17alpha-hydroxyprogesterone production. Both inhibin A and inhibin
      B blocked the inhibitory actions of activins A and B in AC cells, supporting the
      antiactivin model of inhibin action. Inhibin A provided more potent and effective
      antagonism of both activins than did inhibin B, and activin A was less subject to
      antagonism by either inhibin than was activin B. In contrast to the major
      antagonism of activin by both inhibins, only inhibin A antagonized the actions of
      BMP-2, BMP-6, and BMP-7, whereas inhibin B was ineffective against all tested BMP
      isoforms except BMP-7 at high concentrations. These results provide limited
      support for the anti-BMP model of inhibin action and reveal that, relative to
      inhibin A, inhibin B essentially behaves as a selective activin antagonist in AC
      cells. In conclusion, inhibins A and B differentially antagonize the actions of
      activins and BMPs to control adrenocortical C(19) steroid production.

PMID- 16601135
TI  - Src homology 2 (SH2)-containing 5'-inositol phosphatase localizes to podosomes,
      and the SH2 domain is implicated in the attenuation of bone resorption in
      osteoclasts.
AB  - c-Src plays an important role in bone resorption by osteoclasts. Here, we show
      using wild-type and ship(-/-) osteoclasts that Src homology 2 (SH2)-containing 5'
      inositol phosphatase (SHIP) appeared to negatively regulate bone resorption
      activated by c-Src. SHIP was found to localize to podosomes under the influence
      of c-Src, and the presence of either the amino-terminal region comprising the SH2
      domain or the carboxyl-terminal region was sufficient for its localization.
      Although SHIP lacking a functional SH2 domain was still found in podosomes, it
      could not rescue the hyper-bone resorbing activity and hypersensitivity to
      receptor activator of nuclear factor-kappaB ligand in ship(-/-) osteoclasts,
      suggesting that the localization of SHIP to podosomes per se was not sufficient
      and the SH2 domain was indispensable for its function. Cas and c-Cbl, known to
      function in podosomes of osteoclasts, were identified as novel proteins binding
      to the SHIP SH2 domain by mass spectrometric analysis, and this interaction
      appeared to be dependent on the Src kinase activity. These results demonstrate
      that c-Src enhances the translocation of SHIP to podosomes and regulates its
      function there through the SH2 domain, leading to an attenuation of bone
      resorption.

PMID- 16601136
TI  - Evidence for the role of adenosine 5'-triphosphate-binding cassette (ABC)-A1 in
      the externalization of annexin 1 from pituitary folliculostellate cells and ABCA1
      transfected cell models.
AB  - Annexin 1 (ANXA1), a 37-kDa protein, is a member of the superfamily of Ca(2+)-
      and phospholipid-binding annexin proteins. In the anterior pituitary, ANXA1 is
      expressed mainly by folliculostellate (FS) cells and mediates the early delayed
      feedback inhibition exerted by glucocorticoids on the release of ACTH and other
      pituitary hormones. It has been previously demonstrated that TtT/GF cells (a FS
      cell line) express and externalize ANXA1 in response to glucocorticoid treatment.
      However, ANXA1 lacks a cleavable signal sequence and externalization is not
      affected by inhibitors of the secretory pathway. We have previously shown that
      glyburide, an ATP-binding cassette (ABC) transporter inhibitor, inhibits the
      externalization of ANXA1 from TtT/GF cells and pituitary tissue. Here we
      investigated whether ABCA1 is involved in ANXA1 externalization. The use of the
      ABCA1-transporter inhibitors geranyl-geranyl pyrophosphate and
      sulfobromophthalein significantly inhibited ANXA1 externalization. Partial
      silencing of ABCA1 expression in TtT/GF cells by siRNA also significantly
      decreased the amount of cell surface ANXA1. However, anterior pituitary tissue
      from ABCA1-null mice was found to externalize ANXA1 normally. Because
      compensation by other ABC family members may occur in vivo, ANXA1 externalization
      was studied in two transfection models: Xenopus oocytes injected with ABCA1 mRNA
      and AtT20 D1 corticoctroph cells cotransfected with ABCA1-green fluorescent
      protein and ANXA1. ABCA1-expressing oocytes, but not water-injected controls,
      were found to externalize ANXA1. Expression of ABCA1 in AtT20 D1 cells
      significantly increased the amount of cell surface ANXA1, compared with mock
      transfected and ANXA1-only transfected controls. Together these data provide
      evidence for a role of ABCA1 in ANXA1 export.

PMID- 16601137
TI  - Effect of acute aldosterone administration on gene expression profile in the
      heart.
AB  - Aldosterone is known to have a number of direct adverse effects on the heart,
      including fibrosis and myocardial inflammation. However, genetic mechanisms of
      aldosterone action on the heart remain unclear. This paper describes an
      investigation of temporal changes in gene expression profile of the whole heart
      induced by acute administration of a physiologic dose of aldosterone in the
      mouse. mRNA levels of 34,000 known mouse genes were measured at eight time points
      after aldosterone administration using oligonucleotide microarrays and compared
      with those of the control animals who underwent a sham injection. A novel
      software tool (CAGED) designed for analysis of temporal microarray experiments
      using a Bayesian approach was used to identify genes differentially expressed
      between the aldosterone-injected and control group. CAGED analysis identified 12
      genes as having significant differences in their temporal profiles between
      aldosterone-injected and control groups. All of these genes exhibited a decrease
      in expression level 1-3 h after aldosterone injection followed by a brief rebound
      and a return to baseline. These findings were validated by quantitative RT-PCR.
      The differentially expressed genes included phosphatases, regulators of steroid
      biosynthesis, inactivators of reactive oxygen species, and structural proteins.
      Several of these genes are known to functionally mediate biochemical phenomena
      previously observed to be triggered by aldosterone administration, such as
      phosphorylation of ERK1/2. These results provide the first description of cardiac
      genetic response to aldosterone and identify several potential mediators of known
      biochemical sequelae of aldosterone administration in the heart.

PMID- 16601138
TI  - Expression of adiponectin receptors and its possible implication in the human
      endometrium.
AB  - Adiponectin, a pleiotropic cytokine, exerts its effects via the specific
      receptors AdipoR1 and AdipoR2. Whereas circulating adiponectin concentrations
      decrease in women with endometriosis and endometrial cancer, possible effects of
      adiponectin and the presence of the receptors in the endometrium have not been
      determined. In this study, we examined the expression of adiponectin receptors
      AdipoR1 and AdipoR2 in the human endometrium and assessed effects of adiponectin
      in endometrial cells. Expression of AdipoR1 and AdipoR2 in endometrial tissues
      was evaluated by real-time quantitative PCR, in situ hybridization, and Western
      blotting. The effects of adiponectin on phosphorylation of AMP-activated protein
      kinase, a regulator of energy homeostasis, in cultured endometrial stromal cells
      (ESCs) and epithelial cells (EECs) were studied by Western blotting. The effects
      of adiponectin on IL-1beta-induced secretion of IL-6, IL-8, and monocyte
      chemoattractant protein 1 from cultured ESCs were determined using specific
      ELISAs. The expression of AdipoR1 and AdipoR2 was detected in the endometrium.
      The expression of both genes was increased in the midluteal phase, the period of
      embryo implantation. In situ hybridization revealed that both AdipoR1 and AdipoR2
      appeared to be equally expressed in the epithelial cells and in the stromal
      cells. Adiponectin increased phosphorylation of AMP-activated protein kinase in
      ESCs and EECs. Adiponectin decreased IL-1beta-induced secretion of IL-6, IL-8,
      and monocyte chemoattractant protein 1 from ESCs. These findings suggest that
      adiponectin exerts energy-homeostatic and antiinflammatory effects in the
      endometrium, and these effects might be relevant to pathological and
      physiological endometrium-related events such as implantation and endometriosis.

PMID- 16601139
TI  - Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress,
      which may contribute to INS-1 pancreatic beta-cell apoptosis.
AB  - Chronic free fatty acid (FFA) exposure induces pancreatic beta-cell death, which
      may contribute to the development of type 2 diabetes. The mechanisms involved in
      FFA-induced cell death are not completely understood. Here we have investigated
      the effect of FFA on endoplasmic reticulum (ER) stress pathways in INS-1
      pancreatic beta-cells. INS-1 cells exposed to palmitate for 16-24 h under serum
      free conditions showed marked apoptosis and increased protein levels of
      phosphorylated eukaryotic translation initiation factor 2alpha (eIF2alpha),
      activating transcription factor 4 (ATF4), X box-binding protein 1 (XBP-1), and
      C/EBP homologous transcription factor (CHOP) compared with control cells. The
      CHOP transcription factor has been implicated in mediating ER stress-induced
      apoptosis. Unexpectedly, the levels of the ER chaperone proteins Grp78/BiP and
      PDI were not affected by palmitate treatment, suggesting that the cell protective
      aspects of the unfolded protein response (UPR) are not up-regulated by palmitate.
      Palmitate-treated cells had markedly altered distribution of ER chaperones and
      altered ER morphology, suggesting that accumulation of misfolded proteins might
      trigger the ER stress response. In contrast, oleate treatment did not
      significantly induce the UPR pathways, nor was it as detrimental to INS-1 beta
      cells. The results suggest that activation of the UPR may significantly
      contribute to palmitate- but not oleate-induced pancreatic beta-cell death.

PMID- 16601140
TI  - Role of complex cyclin d1/cdk4 in somatostatin subtype 2 receptor-mediated
      inhibition of cell proliferation of a medullary thyroid carcinoma cell line in
      vitro.
AB  - Somatostatin (SRIH) inhibits cell proliferation by interacting with five distinct
      SRIH receptor subtypes (SSTRs) activating several pathways in many tissues. We
      previously demonstrated that SRIH, by activating Src homology-2-containing
      protein, inhibits cell proliferation of the human medullary thyroid carcinoma
      cell line, TT, which expresses all SSTRs. However, the effects of SRIH on cell
      cycle proteins have not been investigated so far. We therefore evaluated the
      effects of SRIH and a selective SSTR2 agonist on cell cycle protein expression,
      mainly focusing on cyclin D1 and its associated kinases. Our data show that SRIH
      and the selective SSTR2 agonist, BIM-23120, reduce cell proliferation and DNA
      synthesis as well as induce a delay of the cell cycle in G(2)/M phase. Moreover,
      treatment with both SRIH and BIM-23120 decreases cyclin D1 levels, with a
      parallel increase in phosphocyclin D1 levels, suggesting protein degradation.
      Moreover, our data show an increase in glycogen synthase kinase-3beta activity,
      which triggers phosphorylation-dependent cyclin D1 degradation. Indeed, we
      observed a reduction in cyclin D1 protein half-life under treatment with SRIH or
      the SSTR2 selective agonist. A reduction in cdk4 protein levels is also observed
      with a parallel reduction in Rb phosphorylation levels at Ser-780. Our data
      indicate that the subtype 2 receptor-mediated antiproliferative effect of SRIH on
      TT cell proliferation may be exerted through a decrease in cyclin D1 levels.

PMID- 16601141
TI  - Induction of type 1 iodothyronine deiodinase to prevent the nonthyroidal illness
      syndrome in mice.
AB  - Essentially all serious illness is associated with a decrease in circulating
      T(3), a condition known as the nonthyroidal illness syndrome. Substantial
      evidence suggests that a contributing factor to this syndrome is a cytokine
      induced decrease in hepatic type 1 iodothyronine deiodinase (D1), an enzyme that
      converts T(4) to T(3). The type 1 deiodinase is induced at the transcriptional
      level by T(3), but illness-associated cytokines block this induction, resulting
      in decreased T(3) and hence a further decline in D1 expression. We demonstrated
      that IL-1 blocks the ability of T(3) to induce D1 in rat hepatocyte primary
      cultures and that forced expression of steroid receptor co- activator 1 (SRC-1)
      prevents this cytokine effect. This led us to test whether forced hepatic
      expression of SRC-1 can prevent the nonthyroidal illness syndrome in vivo.
      Pretreatment of endotoxin-treated mice with an adenovirus that expresses SRC-1,
      compared with a control adenovirus, prevented the endotoxin-induced decreases in
      hepatic D1 and plasma T(3). The data suggest that a cytokine-induced defect in
      T(3) receptor coactivators is an important component of this animal model of
      nonthyroidal illness and that the syndrome can be overcome by forced expression
      of the coactivator.

PMID- 16601142
TI  - Characterization of leptin-responsive neurons in the caudal brainstem.
AB  - The central melanocortin system plays a key role in the regulation of energy
      homeostasis. Neurons containing the peptide precursor proopiomelanocortin (POMC)
      are found at two sites in the brain, the arcuate nucleus of the hypothalamus
      (ARC) and the caudal region of the nucleus of the solitary tract (NTS). ARC POMC
      neurons, which also express cocaine- and amphetamine-regulated transcript (CART),
      are known to mediate part of the response to factors regulating energy
      homeostasis, such as leptin and ghrelin. In contrast, the physiological role(s)
      of the POMC neurons in the caudal brainstem are not well characterized. However,
      development of a transgenic mouse expressing green fluorescent protein under the
      control of the POMC promoter [POMC-enhanced green fluorescent protein (EGFP)
      mouse] has aided the study of these neurons. Indeed, recent studies have shown
      significant activation of NTS POMC-EGFP cells by the gut released satiety factor
      cholecystokinin (CCK). Here we show that peripheral leptin administration induces
      the expression of phospho-signal transducer and activator of transcription 3
      immunoreactivity (pSTAT3-IR), a marker of leptin receptor signaling, in more than
      50% of NTS POMC-EGFP neurons. Furthermore, these POMC-EGFP neurons comprise 30%
      of all pSTAT3-IR cells in the NTS. Additionally, we also show that in contrast to
      the ARC population, NTS POMC-EGFP neurons do not coexpress CART immunoreactivity.
      These data suggest that NTS POMC neurons may participate with ARC POMC cells in
      mediating some of the effects of leptin and thus comprise a novel cell group
      regulated by both long-term adipostatic signals and satiety factors such as CCK.

PMID- 16601143
TI  - Characterization of recombinant Xenopus laevis type I iodothyronine deiodinase:
      substitution of a proline residue in the catalytic center by serine (Pro132Ser)
      restores sensitivity to 6-propyl-2-thiouracil.
AB  - In frogs such as Rana and Xenopus, metamorphosis does not occur in the absence of
      a functional thyroid gland. Previous studies indicated that coordinated
      development in frogs requires tissue and stage-dependent type II and type III
      iodothyronine deiodinase expression patterns to obtain requisite levels of
      intracellular T(3) in tissues at the appropriate stages of metamorphosis. No type
      I iodothyronine deiodinase (D1), defined as T(4) or reverse T(3) (rT3) outer-ring
      deiodinase (ORD) activity with Michaelis constant (K(m)) values in the micromolar
      range and sensitivity to 6-propyl-2-thiouracil (6-PTU), could be detected in
      tadpoles so far. We obtained a X. laevis D1 cDNA clone from brain tissue. The
      complete sequence of this clone (1.1 kb, including poly A tail) encodes an ORF of
      252 amino acid residues with high homology to other vertebrate D1 enzymes. The
      core catalytic center includes a UGA-encoded selenocysteine residue, and the 3'
      untranslated region (about 300 nt) contains a selenocysteine insertion sequence
      element. Transfection of cells with an expression vector containing the full
      length cDNA resulted in generation of significant deiodinase activity in the
      homogenates. The enzyme displayed ORD activity with T(4) (K(m) 0.5 microm) and
      rT3 (K(m) 0.5 microm) and inner-ring deiodinase activity with T(4) (K(m) 0.4
      microm). Recombinant Xenopus D1 was essentially insensitive to inhibition by 6
      PTU (IC(50) > 1 mm) but was sensitive to gold thioglucose (IC(50) 0.1 mum) and
      iodoacetate (IC(50) 10 microm). Because the residue 2 positions downstream from
      the selenocysteine is Pro in Xenopus D1 but Ser in all cloned PTU-sensitive D1
      enzymes, we prepared the Pro132Ser mutant of Xenopus D1. The mutant enzyme showed
      strongly increased ORD activity with T(4) and rT3 (K(m) about 4 microm) and was
      highly sensitive to 6-PTU (IC(50) 2 microm). Little native D1 activity could be
      detected in Xenopus liver, kidney, brain, and gut, but significant D1 mRNA
      expression was observed in juvenile brain and adult liver and kidney. These
      results indicate the existence of a 6-PTU-insensitive D1 enzyme in X. laevis
      tissues, but its role during tadpole metamorphosis remains to be defined.

PMID- 16601144
TI  - Glycogen synthase kinase-3 beta inhibition reduces secondary damage in
      experimental spinal cord trauma.
AB  - Glycogen synthase kinase-3 (GSK-3) has recently been identified as an ubiquitous
      serine-threonine protein kinase that participates in a multitude of cellular
      processes and plays an important role in the pathophysiology of a number of
      diseases. The aim of this study was to investigate the effects of GSK-3beta
      inhibition on the degree of experimental spinal cord trauma induced by the
      application of vascular clips (force of 24 g) to the dura via a four-level T5-T8
      laminectomy. Spinal cord injury (SCI) in mice resulted in severe trauma
      characterized by edema, neutrophil infiltration, production of a range of
      inflammatory mediators, tissue damage, and apoptosis. Treatment of the mice with
      4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a potent and
      selective GSK-3beta inhibitor, significantly reduced the degree of 1) spinal cord
      inflammation and tissue injury (histological score); 2) neutrophil infiltration
      (myeloperoxidase activity); 3) inducible nitric-oxide synthase, nitrotyrosine,
      and cyclooxygenase-2 expression; and 4) and apoptosis (terminal deoxynucleotidyl
      transferase dUTP nick-end labeling staining and Bax and Bcl-2 expression). In a
      separate set of experiments, TDZD-8 significantly ameliorated the recovery of
      limb function (evaluated by motor recovery score). Taken together, our results
      clearly demonstrate that treatment with TDZD-8 reduces the development of
      inflammation and tissue injury associated with spinal cord trauma.

PMID- 16601145
TI  - Subitizing, magnitude representation, and magnitude retrieval in deaf and hearing
      adults.
AB  - This study examines basic number processing (subitizing, automaticity, and
      magnitude representation) as the possible underpinning of mathematical
      difficulties often evidenced in deaf adults. Hearing and deaf participants
      completed tasks to assess the automaticity with which magnitude information was
      activated and retrieved from long-term memory (using a Stroop-like paradigm to
      assess congruity effects), the representational format of magnitude information
      (by analysis of distance and Spatial Numerical Association of Response Codes
      effects), and the ability to rapidly enumerate small sets (subitizing). Both
      groups showed distance effects taken to indicate the use of a visual-spatial
      analog number line representing approximate quantity. Furthermore, both groups
      showed similar patterns of performance on the subitizing tasks and showed similar
      amounts of interference in an analysis of congruity effects. This is taken as
      evidence against the notion that idiosyncratic differences in basic number
      processing account for mathematical difficulties experienced by deaf individuals.

PMID- 16601146
TI  - Caveolae and cell swelling. Focus on "Stimulation by caveolin-1 of the
      hypotonicity-induced release of taurine and ATP at basolateral, but not apical,
      membrane of Caco-2 cells".

PMID- 16601147
TI  - Polyunsaturated fatty acids mobilize intracellular Ca2+ in NT2 human
      teratocarcinoma cells by causing release of Ca2+ from mitochondria.
AB  - In a variety of disorders, overaccumulation of lipid in nonadipose tissues,
      including the heart, skeletal muscle, kidney, and liver, is associated with
      deterioration of normal organ function, and is accompanied by excessive plasma
      and cellular levels of free fatty acids (FA). Increased concentrations of FA may
      lead to defects in mitochondrial function found in diverse diseases. One of the
      most important regulators of mitochondrial function is mitochondrial Ca(2+)
      ([Ca(2+)](m)), which fluctuates in coordination with intracellular Ca(2+)
      ([Ca(2+)](i)). Polyunsaturated FA (PUFA) have been shown to cause [Ca(2+)](i)
      mobilization albeit by unknown mechanisms. We have found that PUFA but not
      monounsaturated or saturated FA cause [Ca(2+)](i) mobilization in NT2 human
      teratocarcinoma cells. Unlike the [Ca(2+)](i) response to the muscarinic G
      protein-coupled receptor agonist carbachol, PUFA-mediated [Ca(2+)](i)
      mobilization in NT2 cells is independent of phospholipase C and inositol-1,4,5
      trisphospate (IP(3)) receptor activation, as well as IP(3)-sensitive internal
      Ca(2+) stores. Furthermore, PUFA-mediated [Ca(2+)](i) mobilization is inhibited
      by the mitochondria uncoupler carboxyl cyanide m-chlorophenylhydrozone. Direct
      measurements of [Ca(2+)](m) with X-rhod-1 and (45)Ca(2+) indicate that PUFA
      induce Ca(2+) efflux from mitochondria. Further studies show that ruthenium red,
      an inhibitor of the mitochondrial Ca(2+) uniporter, blocks PUFA-induced Ca(2+)
      efflux from mitochondria, whereas inhibitors of the mitochondrial permeability
      transition pore cyclosporin A and bongkrekic acid have no effect. Thus PUFA-gated
      Ca(2+) release from mitochondria, possibly via the Ca(2+) uniporter, appears to
      be the underlying mechanism for PUFA-induced [Ca(2+)](i) mobilization in NT2
      cells.

PMID- 16601148
TI  - Enhancement of substrate-gated Cl- currents via rat glutamate transporter EAAT4
      by PMA.
AB  - Glutamate transporters (also called excitatory amino acid transporters, EAAT) are
      important in extracellular homeostasis of glutamate, a major excitatory
      neurotransmitter. EAAT4, a neuronally expressed EAAT in cerebellum, has a large
      portion (approximately 95% of the total L-aspartate-induced currents in human
      EAAT4) of substrate-gated Cl(-) currents, a distinct feature of this EAAT. We
      cloned EAAT4 from rat cerebellum. This molecule was predicted to have eight
      putative transmembrane domains. L-glutamate induced an inward current in oocytes
      expressing this EAAT4 at a holding potential -60 mV. Phorbol 12-myristate 13
      acetate (PMA), a protein kinase C (PKC) activator, significantly increased the
      magnitude of L-glutamate-induced currents but did not affect the apparent
      affinity of EAAT4 for L-glutamate. This PMA-enhanced current had a reversal
      potential -17 mV at extracellular Cl(-) concentration ([Cl(-)](o)) 104 mM with an
      approximately 60-mV shift per 10-fold change in [Cl(-)](o), properties consistent
      with Cl(-)-selective conductance. However, PMA did not change EAAT4 transport
      activity as measured by [(3)H]-L-glutamate. Thus PMA-enhanced Cl(-) currents via
      EAAT4 were not thermodynamically coupled to substrate transport. These PMA
      enhanced Cl(-) currents were partially blocked by staurosporine, chelerythrine,
      and calphostin C, the three PKC inhibitors. Ro-31-8425, a PKC inhibitor that
      inhibits conventional PKC isozymes at low concentrations (nM level), partially
      inhibited the PMA-enhanced Cl(-) currents only at a high concentration (1
      microM). Intracellular injection of BAPTA, a Ca(2+)-chelating agent, did not
      affect the PMA-enhanced Cl(-) currents. 4alpha-Phorbol-12,13-didecanoate, an
      inactive analog of PMA, did not enhance glutamate-induced currents. These data
      suggest that PKC, possibly isozymes other than conventional ones, modulates the
      substrate-gated Cl(-) currents via rat EAAT4. Our results also suggest that
      substrate-gated ion channel activity and glutamate transport activity, two EAAT4
      properties that could modulate neuronal excitability, can be regulated
      independently.

PMID- 16601149
TI  - Potential of fibroblasts to regulate the formation of three-dimensional vessel
      like structures from endothelial cells in vitro.
AB  - The development of vessel-like structures in vitro to mimic as well as to realize
      the possibility of tissue-engineered small vascular networks presents a major
      challenge to cell biologists and biotechnologists. We aimed to establish a three
      dimensional (3-D) culture system with an endothelial network that does not
      require artificial substrates or ECM compounds. By using human skin fibroblasts
      and endothelial cells (ECs) from the human umbilical vein (HUVECs) in diverse
      spheroid coculture strategies, we verified that fibroblast support and modulate
      EC migration, viability, and network formation in a 3-D tissue-like stromal
      environment. In mixed spheroid cultures consisting of human ECs and fibroblasts,
      a complex 3-D network with EC tubular structures, lumen formation, pinocytotic
      activity, and tight junction complexes has been identified on the basis of
      immunohistochemical and transmission electron microscopic imaging. Tubular
      networks with extensions up to 400 mum were achieved. When EC suspensions were
      used, EC migration and network formation were critically affected by the status
      of the fibroblast. However, the absence of EC migration into the center of 14
      day, but not 3-day, precultured fibroblast spheroids could not be attributed to
      loss of F viability. In parallel, it was also confirmed that migrated ECs that
      entered cluster-like formations became apoptotic, whereas the majority of those
      forming vessel-like structures remained viable for >8 days. Our protocols allow
      us to study the nature of tubule formation in a manner more closely related to
      the in vivo situation as well as to understand the basis for the integration of
      capillary networks in tissue grafts and develop methods of quantifying the amount
      of angiogenesis in spheroids using fibroblast and other cells isolated from the
      same patient, along with ECs.

PMID- 16601150
TI  - PIN proteins perform a rate-limiting function in cellular auxin efflux.
AB  - Intercellular flow of the phytohormone auxin underpins multiple developmental
      processes in plants. Plant-specific pin-formed (PIN) proteins and several
      phosphoglycoprotein (PGP) transporters are crucial factors in auxin transport
      related development, yet the molecular function of PINs remains unknown. Here, we
      show that PINs mediate auxin efflux from mammalian and yeast cells without
      needing additional plant-specific factors. Conditional gain-of-function alleles
      and quantitative measurements of auxin accumulation in Arabidopsis and tobacco
      cultured cells revealed that the action of PINs in auxin efflux is distinct from
      PGP, rate-limiting, specific to auxins, and sensitive to auxin transport
      inhibitors. This suggests a direct involvement of PINs in catalyzing cellular
      auxin efflux.

PMID- 16601151
TI  - Polar PIN localization directs auxin flow in plants.
AB  - Polar flow of the phytohormone auxin requires plasma membrane-associated PIN
      proteins and underlies multiple developmental processes in plants. Here we
      address the importance of the polarity of subcellular PIN localization for the
      directionality of auxin transport in Arabidopsis thaliana. Expression of
      different PINs in the root epidermis revealed the importance of PIN polar
      positions for directional auxin flow and root gravitropic growth. Interfering
      with sequence-embedded polarity signals directly demonstrates that PIN polarity
      is a primary factor in determining the direction of auxin flow in meristematic
      tissues. This finding provides a crucial piece in the puzzle of how auxin flow
      can be redirected via rapid changes in PIN polarity.

PMID- 16601152
TI  - Quantum-dot spin-state preparation with near-unity fidelity.
AB  - We have demonstrated laser cooling of a single electron spin trapped in a
      semiconductor quantum dot. Optical coupling of electronic spin states was
      achieved using resonant excitation of the charged quantum dot (trion) transitions
      along with the heavy-light hole mixing, which leads to weak yet finite rates for
      spin-flip Raman scattering. With this mechanism, the electron spin can be cooled
      from 4.2 to 0.020 kelvin, as confirmed by the strength of the induced Pauli
      blockade of the trion absorption. Within the framework of quantum information
      processing, this corresponds to a spin-state preparation with a fidelity
      exceeding 99.8%.

PMID- 16601153
TI  - Recognition of histone H3 lysine-4 methylation by the double tudor domain of
      JMJD2A.
AB  - Biological responses to histone methylation critically depend on the faithful
      readout and transduction of the methyl-lysine signal by "effector" proteins, yet
      our understanding of methyl-lysine recognition has so far been limited to the
      study of histone binding by chromodomain and WD40-repeat proteins. The double
      tudor domain of JMJD2A, a Jmjc domain-containing histone demethylase, binds
      methylated histone H3-K4 and H4-K20. We found that the double tudor domain has an
      interdigitated structure, and the unusual fold is required for its ability to
      bind methylated histone tails. The cocrystal structure of the JMJD2A double tudor
      domain with a trimethylated H3-K4 peptide reveals that the trimethyl-K4 is bound
      in a cage of three aromatic residues, two of which are from the tudor-2 motif,
      whereas the binding specificity is determined by side-chain interactions
      involving amino acids from the tudor-1 motif. Our study provides mechanistic
      insights into recognition of methylated histone tails by tudor domains and
      reveals the structural intricacy of methyl-lysine recognition by two closely
      spaced effector domains.

PMID- 16601155
TI  - FDA centennial.

PMID- 16601154
TI  - Virus-enabled synthesis and assembly of nanowires for lithium ion battery
      electrodes.
AB  - The selection and assembly of materials are central issues in the development of
      smaller, more flexible batteries. Cobalt oxide has shown excellent
      electrochemical cycling properties and is thus under consideration as an
      electrode for advanced lithium batteries. We used viruses to synthesize and
      assemble nanowires of cobalt oxide at room temperature. By incorporating gold
      binding peptides into the filament coat, we formed hybrid gold-cobalt oxide wires
      that improved battery capacity. Combining virus-templated synthesis at the
      peptide level and methods for controlling two-dimensional assembly of viruses on
      polyelectrolyte multilayers provides a systematic platform for integrating these
      nanomaterials to form thin, flexible lithium ion batteries.

PMID- 16601156
TI  - South Korea. Premier science university ousts unpopular president.

PMID- 16601157
TI  - U.S. science policy. Revised NASA media rules promise greater openness.

PMID- 16601158
TI  - Paleontology. Fossil shows an early fish (almost) out of water.

PMID- 16601159
TI  - German science. With friends like CAESAR's, who needs Brutus?

PMID- 16601160
TI  - U.S. ocean policy. Major fisheries bill introduced in House.

PMID- 16601161
TI  - Chemistry. New polymer may rev up the output of fuel cells used to power cars.

PMID- 16601162
TI  - Development and ecology. Villagers drafted into China's model of
      'sustainability'.

PMID- 16601163
TI  - Medicine. Old drug, new hope for Marfan syndrome.

PMID- 16601165
TI  - Scientific misconduct. Even retracted papers endure.

PMID- 16601164
TI  - Scientific misconduct. Cleaning up the paper trail.

PMID- 16601166
TI  - U.S. education policy. NSF board wades into swirling debate on school reform.

PMID- 16601167
TI  - Arab science. Qatar taps wells of knowledge.

PMID- 16601168
TI  - Atmospheric science. Technique from outer space takes on Earth observation.

PMID- 16601174
TI  - The burden of brain disorders.

PMID- 16601176
TI  - Evaluating education effectiveness.

PMID- 16601175
TI  - Evolution of metazoa and fungi.

PMID- 16601177
TI  - Comment on "PDK1 nucleates T cell receptor-induced signaling complex for NF
      kappaB activation".
AB  - We observe that protein kinase C (PKC) is phosphorylated on the activation loop
      at threonine 538 (Thr-538) before T cell activation. Our results are inconsistent
      with the conclusions of Lee et al. (Reports, 1 April 2005, p. 114) that the Thr
      538 phosphorylation of PKC is regulated by T cell receptor activation. Other
      mechanisms, such as autophosphorylation of Thr-219, might orchestrate the
      cellular function of PKC in T cells.

PMID- 16601178
TI  - Priorities and funding. "Knowledge innovation" and the Chinese Academy of
      Sciences.

PMID- 16601179
TI  - Social science. Cooperation, punishment, and the evolution of human institutions.

PMID- 16601180
TI  - Evolution. Reducible complexity.

PMID- 16601181
TI  - Physics. New additions to the Schrodinger cat family.

PMID- 16601182
TI  - Chemistry. Chemistry in a computer: advancing the in silico dream.

PMID- 16601183
TI  - Developmental biology. Mixed messages in early development.

PMID- 16601184
TI  - C-H bond functionalization in complex organic synthesis.
AB  - Direct and selective replacement of carbon-hydrogen bonds with new bonds (such as
      C-C, C-O, and C-N) represents an important and long-standing goal in chemistry.
      These transformations have broad potential in synthesis because C-H bonds are
      ubiquitous in organic substances. At the same time, achieving selectivity among
      many different C-H bonds remains a challenge. Here, we focus on the
      functionalization of C-H bonds in complex organic substrates catalyzed by
      transition metal catalysts. We outline the key concepts and approaches aimed at
      achieving selectivity in complex settings and discuss the impact these reactions
      have on synthetic planning and strategy in organic synthesis.

PMID- 16601185
TI  - Sexual conflict via maternal-effect genes in ZW species.
AB  - In female heterogamous (ZW) species, sex-linked genes coding for maternal
      products that are packaged into the egg open a unique arena for genetic conflict
      that does not occur in male heterogamous (XY) species. Z-linked maternal-effect
      alleles that help sons and harm daughters are expected to go to fixation, as are
      W-linked alleles that help daughters and harm sons. This conflict differs from
      known cases of meiotic drive, because sex-specific ontogeny, physiology, and gene
      expression greatly simplify the genetic interactions that lead to sexual
      conflict. Selection on maternal-effect genes may substantially alter the
      evolution of ZW compared with XY systems.

PMID- 16601186
TI  - Evolution of the eastern tropical Pacific through Plio-Pleistocene glaciation.
AB  - A tropical Pacific climate state resembling that of a permanent El Nino is
      hypothesized to have ended as a result of a reorganization of the ocean heat
      budget approximately 3 million years ago, a time when large ice sheets appeared
      in the high latitudes of the Northern Hemisphere. We report a high-resolution
      alkenone reconstruction of conditions in the heart of the eastern equatorial
      Pacific (EEP) cold tongue that reflects the combined influences of changes in the
      equatorial thermocline, the properties of the thermocline's source waters,
      atmospheric greenhouse gas content, and orbital variations on sea surface
      temperature (SST) and biological productivity over the past 5 million years. Our
      data indicate that the intensification of Northern Hemisphere glaciation
      approximately 3 million years ago did not interrupt an almost monotonic cooling
      of the EEP during the Plio-Pleistocene. SST and productivity in the eastern
      tropical Pacific varied in phase with global ice volume changes at a dominant
      41,000-year (obliquity) frequency throughout this time. Changes in the Southern
      Hemisphere most likely modulated most of the changes observed.

PMID- 16601187
TI  - Cobalt-base high-temperature alloys.
AB  - We have identified cobalt-base superalloys showing a high-temperature strength
      greater than those of conventional nickel-base superalloys. The cobalt-base
      alloys are strengthened by a ternary compound with the L1(2) structure, gamma'
      Co3(Al,W), which precipitates in the disordered gamma face-centered cubic cobalt
      matrix with high coherency and with high melting points. We also identified a
      ternary compound, gamma' Ir3(Al,W), with the L1(2) structure, which suggests that
      the Co-Ir-Al-W-base systems with gamma+gamma' (Co,Ir)3(Al,W) structures offer
      great promise as candidates for next-generation high-temperature materials.

PMID- 16601188
TI  - New dust belts of Uranus: one ring, two ring, red ring, blue ring.
AB  - We compared near-infrared observations of the recently discovered outer rings of
      Uranus with Hubble Space Telescope results. We find that the inner ring, R/2003 U
      2, is red, whereas the outer ring, R/2003 U 1, is very blue. Blue is an unusual
      color for rings; Saturn's enigmatic E ring is the only other known example. By
      analogy to the E ring, R/2003 U 1 is probably produced by impacts into the
      embedded moon Mab, which apparently orbits at a location where nongravitational
      perturbations favor the survival and spreading of submicron-sized dust. R/2003 U
      2 more closely resembles Saturn's G ring, which is red, a typical color for dusty
      rings.

PMID- 16601189
TI  - Evolution of hormone-receptor complexity by molecular exploitation.
AB  - According to Darwinian theory, complexity evolves by a stepwise process of
      elaboration and optimization under natural selection. Biological systems composed
      of tightly integrated parts seem to challenge this view, because it is not
      obvious how any element's function can be selected for unless the partners with
      which it interacts are already present. Here we demonstrate how an integrated
      molecular system-the specific functional interaction between the steroid hormone
      aldosterone and its partner the mineralocorticoid receptor-evolved by a stepwise
      Darwinian process. Using ancestral gene resurrection, we show that, long before
      the hormone evolved, the receptor's affinity for aldosterone was present as a
      structural by-product of its partnership with chemically similar, more ancient
      ligands. Introducing two amino acid changes into the ancestral sequence
      recapitulates the evolution of present-day receptor specificity. Our results
      indicate that tight interactions can evolve by molecular exploitation-recruitment
      of an older molecule, previously constrained for a different role, into a new
      functional complex.

PMID- 16601190
TI  - Phylogeny of the ants: diversification in the age of angiosperms.
AB  - We present a large-scale molecular phylogeny of the ants (Hymenoptera:
      Formicidae), based on 4.5 kilobases of sequence data from six gene regions
      extracted from 139 of the 288 described extant genera, representing 19 of the 20
      subfamilies. All but two subfamilies are recovered as monophyletic. Divergence
      time estimates calibrated by minimum age constraints from 43 fossils indicate
      that most of the subfamilies representing extant ants arose much earlier than
      previously proposed but only began to diversify during the Late Cretaceous to
      Early Eocene. This period also witnessed the rise of angiosperms and most
      herbivorous insects.

PMID- 16601191
TI  - Platelet-derived serotonin mediates liver regeneration.
AB  - The liver can regenerate its volume after major tissue loss. In a mouse model of
      liver regeneration, thrombocytopenia, or impaired platelet activity resulted in
      the failure to initiate cellular proliferation in the liver. Platelets are major
      carriers of serotonin in the blood. In thrombocytopenic mice, a serotonin agonist
      reconstituted liver proliferation. The expression of 5-HT2A and 2B subtype
      serotonin receptors in the liver increased after hepatectomy. Antagonists of 5
      HT2A and 2B receptors inhibited liver regeneration. Liver regeneration was also
      blunted in mice lacking tryptophan hydroxylase 1, which is the rate-limiting
      enzyme for the synthesis of peripheral serotonin. This failure of regeneration
      was rescued by reloading serotonin-free platelets with a serotonin precursor
      molecule. These results suggest that platelet-derived serotonin is involved in
      the initiation of liver regeneration.

PMID- 16601192
TI  - The competitive advantage of sanctioning institutions.
AB  - Understanding the fundamental patterns and determinants of human cooperation and
      the maintenance of social order in human societies is a challenge across
      disciplines. The existing empirical evidence for the higher levels of cooperation
      when altruistic punishment is present versus when it is absent systematically
      ignores the institutional competition inherent in human societies. Whether
      punishment would be deliberately adopted and would similarly enhance cooperation
      when directly competing with nonpunishment institutions is highly controversial
      in light of recent findings on the detrimental effects of punishment. We show
      experimentally that a sanctioning institution is the undisputed winner in a
      competition with a sanction-free institution. Despite initial aversion, the
      entire population migrates successively to the sanctioning institution and
      strongly cooperates, whereas the sanction-free society becomes fully depopulated.
      The findings demonstrate the competitive advantage of sanctioning institutions
      and exemplify the emergence and manifestation of social order driven by
      institutional selection.

PMID- 16601193
TI  - Darwinian evolution can follow only very few mutational paths to fitter proteins.
AB  - Five point mutations in a particular beta-lactamase allele jointly increase
      bacterial resistance to a clinically important antibiotic by a factor of
      approximately 100,000. In principle, evolution to this high-resistance beta
      lactamase might follow any of the 120 mutational trajectories linking these
      alleles. However, we demonstrate that 102 trajectories are inaccessible to
      Darwinian selection and that many of the remaining trajectories have negligible
      probabilities of realization, because four of these five mutations fail to
      increase drug resistance in some combinations. Pervasive biophysical pleiotropy
      within the beta-lactamase seems to be responsible, and because such pleiotropy
      appears to be a general property of missense mutations, we conclude that much
      protein evolution will be similarly constrained. This implies that the protein
      tape of life may be largely reproducible and even predictable.

PMID- 16601194
TI  - Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan
      syndrome.
AB  - Aortic aneurysm and dissection are manifestations of Marfan syndrome (MFS), a
      disorder caused by mutations in the gene that encodes fibrillin-1. Selected
      manifestations of MFS reflect excessive signaling by the transforming growth
      factor-beta (TGF-beta) family of cytokines. We show that aortic aneurysm in a
      mouse model of MFS is associated with increased TGF-beta signaling and can be
      prevented by TGF-beta antagonists such as TGF-beta-neutralizing antibody or the
      angiotensin II type 1 receptor (AT1) blocker, losartan. AT1 antagonism also
      partially reversed noncardiovascular manifestations of MFS, including impaired
      alveolar septation. These data suggest that losartan, a drug already in clinical
      use for hypertension, merits investigation as a therapeutic strategy for patients
      with MFS and has the potential to prevent the major life-threatening
      manifestation of this disorder.

PMID- 16601195
TI  - Deciphering the genetics of stature--another piece of the puzzle.

PMID- 16601196
TI  - Klinefelter's syndrome--a microcosm of male reproductive health.

PMID- 16601197
TI  - What's good for the goose's skeleton is good for the gander's skeleton.

PMID- 16601198
TI  - Uncoupling protein 3 and human metabolism.

PMID- 16601201
TI  - KREPA4, an RNA binding protein essential for editosome integrity and survival of
      Trypanosoma brucei.
AB  - The 20S editosome, a multiprotein complex, catalyzes the editing of most
      mitochondrial mRNAs in trypanosomatids by uridylate insertion and deletion. RNAi
      mediated inactivation of expression of KREPA4 (previously TbMP24), a component of
      the 20S editosome, in procyclic form Trypanosoma brucei resulted in inhibition of
      cell growth, loss of RNA editing, and disappearance of 20S editosomes. Levels of
      MRP1 and REAP-1 proteins, which may have roles in editing but are not editosome
      components, were unaffected. Tagged KREPA4 protein is incorporated into 20S
      editosomes in vivo with no preference for either insertion or deletion
      subcomplexes. Consistent with its S1-like motif, recombinant KREPA4 protein binds
      synthetic gRNA with a preference for the 3' oligo (U) tail. These data suggest
      that KREPA4 is an RNA binding protein that may be specific for the gRNA Utail and
      also is important for 20S editosome stability.

PMID- 16601202
TI  - hNaf1 is required for accumulation of human box H/ACA snoRNPs, scaRNPs, and
      telomerase.
AB  - The human telomerase ribonucleoprotein particle (RNP) shares with box H/ACA small
      Cajal body (sca)RNPs and small nucleolar (sno)RNPs the proteins dyskerin, hGar1,
      hNhp2, and hNop10. How dyskerin, hGar1, hNhp2, and hNop10 assemble with box H/ACA
      scaRNAs, snoRNAs, and the RNA component of telomerase (hTR) in vivo remains
      unknown. In yeast, Naf1p interacts with H/ACA snoRNP proteins and may promote
      assembly of Cbf5p (the yeast ortholog of dyskerin) with nascent pre-snoRNAs. Here
      we show that the human HsQ96HR8 protein, thereafter termed hNaf1, can
      functionally replace endogenous Naf1p in yeast. HeLa hNaf1 associates with
      dyskerin and hNop10 as well as box H/ACA scaRNAs, snoRNAs, and hTR. Reduction of
      hNaf1 steady-state levels by RNAi significantly lowers accumulation of these
      components of box H/ACA scaRNP, snoRNP, and telomerase. hNaf1 is found
      predominantly in numerous discrete foci in the nucleoplasm and fails to
      accumulate within Cajal bodies or nucleoli. Altogether, these results suggest
      that hNaf1 intervenes in early assembly steps of human box H/ACA RNPs, including
      telomerase.

PMID- 16601203
TI  - Nucleobase catalysis in the hairpin ribozyme.
AB  - RNA catalysis is important in the processing and translation of RNA molecules,
      yet the mechanisms of catalysis are still unclear in most cases. We have studied
      the role of nucleobase catalysis in the hairpin ribozyme, where the scissile
      phosphate is juxtaposed between guanine and adenine bases. We show that a
      modified ribozyme in which guanine 8 has been substituted by an imidazole base is
      active in both cleavage and ligation, with ligation rates 10-fold faster than
      cleavage. The rates of both reactions exhibit bell-shaped dependence on pH, with
      pK(a) values of 5.7 +/- 0.1 and 7.7 +/- 0.1 for cleavage and 6.1 +/- 0.3 and 6.9
      +/- 0.3 for ligation. The data provide good evidence for general acid-base
      catalysis by the nucleobases.

PMID- 16601204
TI  - Functions of hUpf3a and hUpf3b in nonsense-mediated mRNA decay and translation.
AB  - The exon-junction complex (EJC) components hUpf3a and hUpf3b serve a dual
      function: They promote nonsense-mediated mRNA decay (NMD), and they also regulate
      translation efficiency. Whether these two functions are interdependent or
      independent of each other is unknown. We characterized the function of the hUpf3
      proteins in a lambdaN/boxB-based tethering system. Despite the high degree of
      sequence similarity between hUpf3b and hUpf3a, hUpf3a is much less active than
      hUpf3b to induce NMD and to stimulate translation. We show that induction of NMD
      by hUpf3 proteins requires interaction with Y14, Magoh, BTZ, and eIF4AIII. The
      protein region that mediates this interaction and discriminates between hUpf3a
      and hUpf3b in NMD function is located in the C-terminal domain and fully
      contained within a small sequence that is highly conserved in Upf3b but not Upf3a
      proteins. Stimulation of translation is independent of this interaction and is
      determined by other regions of the hUpf3 protein, indicating the presence of
      different downstream pathways of hUpf3 proteins either in NMD or in translation.

PMID- 16601205
TI  - The coiled-coil domain of the Nop56/58 core protein is dispensable for sRNP
      assembly but is critical for archaeal box C/D sRNP-guided nucleotide methylation.
AB  - Archaeal box C/D sRNAs guide the methylation of specific nucleotides in archaeal
      ribosomal and tRNAs. Three Methanocaldococcus jannaschii sRNP core proteins
      (ribosomal protein L7, Nop56/58, and fibrillarin) bind the box C/D sRNAs to
      assemble the sRNP complex, and these core proteins are essential for nucleotide
      methylation. A distinguishing feature of the Nop56/58 core protein is the coiled
      coil domain, established by alpha-helices 4 and 5, that facilitates Nop56/58 self
      dimerization in vitro. The function of this coiled-coil domain has been assessed
      for box C/D sRNP assembly, sRNP structure, and sRNP-guided nucleotide methylation
      by mutating or deleting this protein domain. Protein pull-down experiments
      demonstrated that Nop56/58 self-dimerization and Nop56/58 dimerization with the
      core protein fibrillarin are mutually exclusive protein:protein interactions.
      Disruption of Nop56/58 homodimerization by alteration of specific amino acids or
      deletion of the entire coiled-coil domain had no obvious effect upon core protein
      binding and sRNP assembly. Site-directed mutation of the Nop56/58
      homodimerization domain also had no apparent effect upon either box C/D RNP- or
      C'/D' RNP-guided nucleotide modification. However, deletion of this domain
      disrupted guided methylation from both RNP complexes. Nuclease probing of the
      sRNP assembled with Nop56/58 proteins mutated in the coiled-coil domain indicated
      that while functional complexes were assembled, box C/D and C'/D' RNPs were
      altered in structure. Collectively, these experiments revealed that the self
      dimerization of the Nop56/58 coiled-coil domain is not required for assembly of a
      functional sRNP, but the coiled-coil domain is important for the establishment of
      wild-type box C/D and C'/D' RNP structure essential for nucleotide methylation.

PMID- 16601206
TI  - Assessing IRES activity in the HIF-1alpha and other cellular 5' UTRs.
AB  - Dicistronic reporter plasmids, such as the dual luciferase-containing pR-F
      plasmid, have been widely used to assay cellular and viral 5' untranslated
      regions (UTRs) for IRES activity. We found that the pR-F dicistronic reporter
      containing the 5' UTRs from HIF-1alpha, VEGF, c-myc, XIAP, VEGFR-1, or Egr-1 UTRs
      all produce the downstream luciferase predominantly as a result of cryptic
      promoter activity that is activated by the SV40 enhancer elements in the plasmid.
      RNA transfection experiments using dicistronic or uncapped RNAs, which avoid the
      complication of cryptic promoter activity, indicate that the HIF-1alpha, VEGF, c
      myc, and XIAP UTRs do have some IRES activity, although the activity was much
      less than that of the viral EMCV IRES. The translation of transfected
      monocistronic RNAs containing these cellular UTRs was greatly enhanced by the
      presence of a 5' cap, raising questions as to the strength or mechanism of IRES
      mediated translation in these assays.

PMID- 16601207
TI  - CUG-BP binds to RNA substrates and recruits PARN deadenylase.
AB  - CUG-BP is the human homolog of the Xenopus EDEN-BP, which was shown previously to
      bind to mRNAs, such as c-mos, that exhibit rapid deadenylation following
      fertilization of the oocyte. While several studies have focused on roles of CUG
      BP as a splicing or translation regulator in mammalian cells, its role in mRNA
      decay has not been examined in detail. Here, we have used an in vitro
      deadenylation assay to dissect the function of CUG-BP in the decay of two ARE
      containing mRNAs: c-fos and TNFalpha. CUG-BP binds specifically to both of these
      RNAs and stimulates poly(A) shortening by PARN. Moreover, CUG-BP interacts with
      PARN in extracts by coimmunoprecipitation, and this interaction can be
      recapitulated using recombinant proteins. CUG-BP, therefore, is the first RNA
      binding protein shown to directly recruit a deadenylase to an RNA substrate.

PMID- 16601209
TI  - Secular trends in stroke incidence and survival, and the occurrence of dementia.

PMID- 16601210
TI  - Increasing rates of dementia at time of declining mortality from stroke.
AB  - BACKGROUND AND PURPOSE: Stroke is associated with increased risk of dementia.
      There has been a decline in mortality from stroke among persons 65 and over in
      recent decades in the US. It is not clear, however, how this process has affected
      incidence of various dementias. METHODS: We evaluated over time changes in stroke
      admission rates and survival, and in rates of newly diagnosed dementias
      (Alzheimer disease, senile, and cerebrovascular disease-related dementia) in
      persons with and without stroke aged 65 and over, using Medicare inpatient
      records, 1984 to 2001, linked to the National Long-Term Care Survey (about
      380,000 person-years totally). RESULTS: Age-adjusted stroke rate increased from
      0.0066 to 0.008 (P=0.08) from 1984-1990 to 1991-2001. One-year survival after
      stroke improved from 53% in 1984 to 1990 to 65% in 1991 to 1996 (P<0.0001). Age
      standardized rate of diagnosed dementias increased from 0.0062 in 1984 to 1990 to
      0.0095 in 1991 to 2000 (P=0.001). Among stroke patients the rate rose from 0.043
      to 0.080. The relative increase in risk was largest for cerebrovascular disease
      related dementia (3.68). For senile dementia, the increase was small and not
      significant. Rates of dementia among persons without stroke rose mainly
      attributable to Alzheimer disease. CONCLUSIONS: Mortality from stroke declined
      mainly because of declining stroke case-fatality. In parallel, the rate of
      diagnosed dementia increased. The increase was larger for persons with stroke
      compared with stroke-free population. Improved survival from stroke may
      contribute to this trend. Other contributing factors may include better
      diagnostics, an increased propensity to make the diagnosis, and increasing
      dementia risk attributable to factors other than stroke.

PMID- 16601211
TI  - Poststroke C-reactive protein is a powerful prognostic tool among candidates for
      thrombolysis.
AB  - BACKGROUND AND PURPOSE: After acute stroke, an increased level of C-reactive
      protein (CRP) measured at discharge predicts unfavorable outcome. We sought to
      investigate whether CRP measured before tissue plasminogen activator (tPA)
      treatments may add prognostic information to guide stroke thrombolysis. METHODS:
      Our target was 151 consecutive patients with an ischemic stroke involving the
      middle cerebral artery territory who received tPA within 3 hours of symptom
      onset. High-sensitivity CRP was measured before tPA administration, and CRP gene
      polymorphisms were determined (G1059C and C1444T). Functional outcome was
      evaluated by 3-month modified Rankin Scale (mRS). RESULTS: A total of 143 tPA
      treated patients were valid for analyses after exclusion of those with
      inflammatory diseases and those probably infected (CRP >6 mg/dL). Patients with
      history of previous stroke, hypertension, or atrial fibrillation had higher
      levels of CRP (P<0.05). CRP was higher in patients who died after thrombolysis
      (n=19) than in survivors (0.85 versus 0.53 mg/dL; P=0.002). Among the 94 patients
      with proximal middle cerebral artery occlusions, CRP level was 0.53 for 81
      survivors versus 0.81 mg/dL for 13 who died (P=0.001). CRP-survival association
      was found even among patients who recanalized by the end of tPA infusion
      (P=0.007). A correlation between CRP and mRS was found (r=0.36, P=0.02), although
      CRP polymorphisms were not related to neurological outcome. In a logistic
      regression model, CRP (odds ratio=8.51; 95% CI, 2.16 to 33.5; P=0.002) and age
      (odds ratio=6.25; 95% CI, 1.44 to 27.19; P=0.015) were the only baseline
      mortality predictors. CONCLUSIONS: Admission CRP predicts mortality among tPA
      treated stroke patients. Very early recanalization does not ameliorate the
      negative prognostic impact of elevated CRP.

PMID- 16601212
TI  - Reducing the risk of dementia: efficacy of long-term treatment of hypertension.
AB  - BACKGROUND AND PURPOSE: The efficacy of treating older persons for hypertension
      remains controversial. Although clinical trials suggest no short-term harm, or
      some benefits, there are little data on the effect on cognitive function of long
      term antihypertensive treatment. We evaluated the risk of dementia and cognitive
      decline associated with duration of antihypertensive treatment. METHODS: Data are
      from the Honolulu Asia Aging Study on Japanese American men followed since 1965.
      The subjects included in this analysis were hypertensive from midlife and
      dementia-free in 1991 (mean age 76.7 years). In 1991, 1994 and 1997, global
      cognitive function was assessed with the Cognitive Abilities Screening Instrument
      (CASI) and dementia by a standardized examination using international criteria.
      The sample was grouped by treatment duration (never-treated hypertensives (NTH),
      <5 years, 5 to 12 years, >12 years). Normotensive subjects up to 1991 were
      included in the analysis as a control group. RESULTS: For each additional year of
      treatment there was a reduction in the risk of incident dementia (hazard ratio
      [HR]=0.94, 95% CI, 0.89 to 0.99). The risk for dementia in subjects with >12
      years of treatment was lower compared to NTH (HR for dementia=0.40; 95% CI, 0.22
      to 0.75 and for Alzheimer disease HR=0.35; 95% CI, 0.16 to 0.78) and was similar
      to the normotensives. Nondemented subjects with 5 to 12 years of treatment had
      lower yearly CASI decline compared to NTH. CONCLUSIONS: Results suggest that in
      hypertensive men, the duration of the antihypertensive treatment is associated
      with a reduced risk for dementia and cognitive decline.

PMID- 16601213
TI  - Health-related quality of life among young adults with ischemic stroke on long
      term follow-up.
AB  - BACKGROUND AND PURPOSE: We sought to compare health-related quality of life
      (HRQoL) in young adults with ischemic stroke on long-term follow-up with controls
      and to evaluate HRQoL in clinically relevant patient subgroups. METHODS: HRQoL
      was determined with the use of the 8 subscales of the Short-Form General Health
      Survey (SF-36). Subgroups of patients were defined by sex, age, functional status
      (modified Rankin Scale), marital status, education, depression (Montgomery-Asberg
      Depression Rating Scale), and fatigue (Fatigue Severity Scale). SF-36 scores
      among patients were compared with SF-36 scores among age- and sex-matched
      controls and SF-36 scores available from the general Norwegian population.
      RESULTS: SF-36 scores were obtained after a mean follow-up of 6.0 years among 190
      young adults with ischemic stroke during 1988-1997 and among 215 responding
      controls (55%). The difference in HRQoL between patients, controls, and the
      general Norwegian population was restricted mainly to the 3 subscales physical
      functioning, general health, and social functioning (P<0.001). Subgroup analysis
      showed significantly reduced scores for all SF-36 items among patients who were
      depressed, suffered from fatigue, or unemployed. Linear regression analysis
      showed that fatigue and depression were major independent variables correlated
      with low HRQoL. CONCLUSIONS: Compared with controls and the general Norwegian
      population, low level of HRQoL among young adults with ischemic stroke was most
      pronounced in regard to physical functioning. Early identification and treatment
      of depression, fatigue, and physical disability may potentially improve HRQoL
      among stroke patients.

PMID- 16601214
TI  - Antihypertensive therapy and cognition: more questions than answers.

PMID- 16601216
TI  - Does the Merci Retriever work? For.

PMID- 16601215
TI  - Alcohol intake, carotid plaque, and cognition: the Northern Manhattan Study.
AB  - BACKGROUND AND PURPOSE: Moderate alcohol intake has been associated with better
      cognitive performance, implicating vascular and neurodegenerative processes. Few
      studies to clarify the importance of vascular disease have included direct
      measures of atherosclerosis or minority populations at higher risk of vascular
      disease and dementia. METHODS: The Northern Manhattan Study includes stroke-free
      community based Hispanic (54%), black (25%), and white (22%) participants. We
      performed a cross-sectional study of alcohol intake and performance on the Mini
      Mental State Examination (MMSE) in subjects with sonographic measurement of
      maximal carotid plaque thickness and adjusted for sociodemographic and vascular
      risk factors. RESULTS: The median MMSE score was 27 (interquartile range 24 to
      29; n=2215). Reported alcohol intake was divided into 5 groups: never (n=509),
      past (n=494), <1 drink/week (n=300), 1/week to < or =2 drinks/day (n=796), and >2
      drinks/day (n=116). Drinking 1 drink weekly up to 2 daily was associated with
      better performance on the MMSE (odds ratio=1.19; 95% CI, 1.10 to 1.26) compared
      with nondrinkers in women (P< or =0.0001) but not in men, adjusting for
      sociodemographic and vascular risk factors. Maximal carotid plaque thickness
      (mean 1.1 mm; SD 1.2 mm) was not associated with alcohol intake and did not
      mediate the relationship between alcohol and cognition. CONCLUSIONS: Moderate
      alcohol consumption was independently associated with better cognitive
      performance in women from this multiethnic sample. Carotid plaque was not a
      mediator of this association suggesting alcohol may impact cognition through a
      separate vascular or degenerative pathway.

PMID- 16601217
TI  - Outcome of carotid stenting versus endarterectomy: a case-control study.
AB  - BACKGROUND AND PURPOSE: To compare perioperative and midterm results of carotid
      artery stenting (CAS) versus carotid endarterectomy (CEA) in similar cohorts of
      patients, a retrospectively matched case-control study was performed. METHODS:
      Three hundred and one case subjects undergoing CAS with cerebral protection and
      301 concurrent matched-controls undergoing CEA were examined. Matching was by
      sex, age (+/-2 years), symptoms and coronary disease. RESULTS: The 30-day
      disabling stroke/death rate was 2.6% in the CAS group versus 1.3% in the CEA
      group (odds ratio [OR] 2; 95% CI, 0.54 to 9.35; P=0.4). CAS patients had a
      significantly higher risk of periprocedural stroke (7.9% versus 2.3%; OR, 5.2;
      95% CI, 1.7 to 18; P=0.001) than CEA patients. However, there was a decreasing
      trend in 30-day neurological event rates for the last 201 CAS matched cases: 5.4%
      versus 1.9% (OR 2.8; 95% CI, 0.8 to 10.2; P=0.1). Fifty percent of CAS disabling
      strokes occurred during cannulation of epiaortic vessels before placement of
      cerebral protection. Conditional multivariate analysis revealed CAS as a
      predictor of 30-day stroke (hazard ratios [HR] 3.9; 95% CI, 1.6 to 9.4; P=0.002)
      but not of 30-day disabling stroke/death (HR 3.6; 95% CI, 0.93 to 13.9; P=0.06).
      Restenosis free intervals at 36 months were 93.6% versus 92.1% for CAS and CEA,
      respectively, (P=0.6). CONCLUSIONS: When comparing CAS with CEA, the risk of any
      neurological events is still higher, particularly during catheterism and
      ballooning. The effect of the learning curve related to technical expertise and
      patient selection may influence the outcome of CAS versus CEA. In the midterm the
      restenosis rate of CAS compares favorably to CEA.

PMID- 16601218
TI  - Feedback and cognition in arm motor skill reacquisition after stroke.
AB  - BACKGROUND AND PURPOSE: A debated subject in stroke rehabilitation relates to the
      best type of training approach for motor recovery. First, we analyzed the effects
      of repetitive movement practice in 2 feedback conditions (knowledge of results
      [KR]; knowledge of performance, [KP]) on reacquisition of reaching. Second, we
      evaluated the impact of cognitive impairment on motor relearning ability.
      METHODS: A randomized controlled clinical trial was conducted in Montreal-area
      rehabilitation centers between 1998 and 2003 with 37 patients with chronic
      hemiparesis. Patients were randomly assigned to 3 groups: (1) KR (n=14) practiced
      a reaching task involving 75 repetitions per day, 5 days per week for 2 weeks,
      with 20% KR about movement precision; (2) KP (n=14) trained on the same task and
      schedule as KR but with faded KP about joint motions; and (3) control (C; n=9)
      practiced a nonreaching task. Physical (motor impairment, function) and kinematic
      (movement time, precision, segmentation, variability) variables were assessed
      before and after (immediately, 1 month) practice. Cognitive functions (memory,
      attention, mental flexibility, planning) were also evaluated. RESULTS: Kinematic
      gains in KR (precision) and KP (time, variability) exceeded those in C and
      depended on memory and mental flexibility deficits. In KP, more severely impaired
      patients made the most clinical gains (>2xC), which were related to memory and
      planning abilities. CONCLUSIONS: Use of KP during repetitive movement practice
      resulted in better motor outcomes. Stroke severity together with cognitive
      impairments are important factors for choosing motor rehabilitation interventions
      after stroke.

PMID- 16601219
TI  - AT1 receptor blockade regulates the local angiotensin II system in cerebral
      microvessels from spontaneously hypertensive rats.
AB  - BACKGROUND AND PURPOSE: Blockade of angiotensin II AT1 receptors in cerebral
      microvessels protects against brain ischemia and inflammation. In this study, we
      tried to clarify the presence and regulation of the local renin-angiotensin
      system (RAS) in brain microvessels in hypertension. METHODS: Spontaneously
      hypertensive rats (SHR) and Wistar Kyoto (WKY) controls were treated with an AT1
      receptor antagonist (candesartan, 0.3 mg/kg per day) via subcutaneous osmotic
      minipumps for 4 weeks. The expression and localization of RAS components and the
      effect of AT1 receptor blockade were assessed by Affymetrix microarray, qRT-PCR,
      Western blots, immunohistochemistry and immunofluorescence. RESULTS: We found
      transcripts of most of RAS components in our microarray database, and confirmed
      their expression by qRT-PCR. Angiotensinogen (Aogen), angiotensin-converting
      enzyme (ACE) and AT1 receptors were localized to the endothelium. There was no
      evidence of AT2 receptor localization in the microvascular endothelium. In SHR,
      (pro)renin receptor mRNA and AT1 receptor mRNA and protein expression were
      higher, whereas Aogen, ACE mRNA and AT2 receptor mRNA and protein expression were
      lower than in WKY rats. Candesartan treatment increased Aogen, ACE and AT2
      receptor in SHR, and increased ACE and decreased Aogen in WKY rats, without
      affecting the (pro)renin and AT1 receptors. CONCLUSIONS: Increased (pro)renin and
      AT1 receptor expression in SHR substantiates the importance of the local RAS
      overdrive in the cerebrovascular pathophysiology in hypertension. AT1 receptor
      blockade and increased AT2 receptor stimulation after administration of
      candesartan may contribute to the protection against brain ischemia and
      inflammation.

PMID- 16601220
TI  - Effect of a new inhibitor of the synthesis of 20-HETE on cerebral ischemia
      reperfusion injury.
AB  - BACKGROUND AND PURPOSE: Arachidonic acid that is released following cerebral
      ischemia can be metabolized to 20-hydroxyeicosatetraenoic acid (20-HETE). 20-HETE
      is a potent vasoconstrictor that may contribute to ischemic injury. This study
      examined the effects of blockading the synthesis of 20-HETE with TS-011 on
      infarct size after transient occlusion of the middle cerebral artery (MCAO) of
      rats and after thromboembolic stroke in monkeys. METHODS: Rats were treated with
      TS-011 or vehicle at various times after MCAO. Infarct size was measured by 2,3,5
      triphenyltetrazolium chloride (TTC) staining and plasma levels of 20-HETE were
      determined by liquid chromatography mass spectrometry (LC/MS). The effect of TS
      011 on infarct size was also studied in monkeys after introduction of a clot into
      the internal carotid artery. RESULTS: Plasma levels of 20-HETE increased after
      MCAO in rats. TS-011 (0.01 to 1.0 mg/kg per hour) reduced infarct volume by 40%.
      Chronic administration of TS-011 for 7 days reduced neurological deficits after
      MCAO in rats. TS-011 given in combination with tissue plasminogen activator also
      improved neurological outcome in the stroke model in monkeys. CONCLUSIONS: These
      results suggest that blockade of the formation of 20-HETE with TS-011 may be
      useful for the treatment of ischemic stroke.

PMID- 16601221
TI  - Why does acute hyperglycemia worsen the outcome of transient focal cerebral
      ischemia? Role of corticosteroids, inflammation, and protein O-glycosylation.
AB  - BACKGROUND AND PURPOSE: Hyperglycemia adversely affects the outcome of stroke.
      Global ischemia data support that the harmful effect of hyperglycemia is mediated
      by glucose-induced elevated plasma glucocorticoids. Here we sought to evaluate
      the negative effects of hyperglycemia on transient focal ischemia in the rat, and
      to test whether these could be prevented by inhibition of either corticosteroid
      production or neutrophil infiltration. METHODS: Sprague-Dawley rats (n=217) were
      used. Ischemia was induced by 1 hour middle cerebral artery occlusion (n=196).
      Acute hyperglycemia was induced by IP injection of dextrose 30 minutes before
      ischemia. Neutrophil infiltration was blocked by neutropenia with vinblastine.
      Corticosterone synthesis was inhibited by chemical adrenalectomy with metyrapone.
      We measured MRI lesion and tissue infarct volumes, evaluated the neurological
      function, brain myeloperoxidase and matrix metalloproteinase-9 activities, and
      protein O-glycosylation. RESULTS: Hyperglycemia significantly enhanced MRI
      diffusion-weighted imaging alterations, increased cortical, but not subcortical,
      infarct volume, worsened neurological score, and enhanced brain myeloperoxidase
      and matrix metalloproteinase-9 activities. Metyrapone did not prevent
      hyperglycemic brain damage despite successful reduction of plasma corticosterone.
      Yet, metyrapone tended to reduce cortical infarction and apparent diffusion
      coefficient lesion volume, indicating some negative contribution of
      corticosterone. Blocking neutrophil infiltration was also ineffective to prevent
      the harmful effect of hyperglycemia. A new finding was that O-linked
      glycosylation of cerebral proteins was increased under hyperglycemia.
      CONCLUSIONS: In transient middle cerebral artery occlusion, the hyperglycemia
      exacerbated brain damage cannot be fully explained by the negative effects of
      plasma corticosteroids or neutrophil infiltration. The contribution of other
      intrinsic effects of high glucose, such as brain protein O-glycosylation,
      deserves further investigation.

PMID- 16601222
TI  - Endogenous expression of C-reactive protein is increased in active (ulcerated
      noncomplicated) human carotid artery plaques.
AB  - BACKGROUND AND PURPOSE: There is growing evidence suggesting that C-reactive
      protein (CRP) is an effecter molecule able to induce and promote
      atherothrombosis. The presence of CRP in atherosclerotic plaques may reflect
      local production or infiltration from circulating CRP increased in general
      inflammatory responses. Our aim was to analyze the presence of CRP in human
      advanced carotid artery plaques with differential anatomo-pathological
      characteristics and to assess local expression of CRP and other proinflammatory
      genes in these lesions. METHODS: Human carotid artery specimens from 38 patients
      undergoing scheduled endarterectomy were classified into 3 groups: ulcerated
      (noncomplicated) (UNC, n=19), fibrous (F, n=12) and ulcerated
      (complicated/hemorrhagic) plaques (UC, n=7). The presence of CRP was evaluated by
      immunohistochemistry, and plasma samples were screened for circulating high
      sensitivity C-reactive protein. TaqMan Low-density Arrays were used for study of
      genes related to inflammation (CRP, interleukin-6, macrophage colony-stimulating
      factor-1, monocyte chemotactic protein-1, cyclooxygenase-2). RESULTS: CRP mRNA
      levels were predominantly detected in UNC-high risk plaques but not in UC
      (P=0.001). UNC also exhibit the highest expression levels of other genes involved
      in the inflammatory responses: cyclooxygenase-2 (P<0.005 versus F and versus UC),
      IL-6 (P<0.005 versus F and versus UC) and monocyte chemoattractant protein-1
      (P<0.01 versus F and versus UC). Plaque CRP mRNA levels correlated with
      immunohistochemical findings but were independent of plasma high-sensitivity CRP.
      In UNC plaques endothelial cells and inflammatory cells were strongly positive
      for CRP around areas of newly formed microvessels. CONCLUSIONS: In human high
      risk carotid artery plaques (UNC) CRP expression reflects an active
      proinflammatory stage. Local synthesis of CRP could be involved in plaque
      neovascularization and increased risk of hemorrhagic transformation.

PMID- 16601224
TI  - Does the Merci Retriever work? Against.

PMID- 16601225
TI  - Thrombin and NAD(P)H oxidase-mediated regulation of CD44 and BMP4-Id pathway in
      VSMC, restenosis, and atherosclerosis.
AB  - To characterize novel signaling pathways that underlie NAD(P)H oxidase-mediated
      signaling in atherosclerosis, we first examined differences in thrombin-induced
      gene expression between wild-type and p47phox(-/-) (NAD[P]H oxidase-deficient)
      VSMC. Of the 9000 genes analyzed by cDNA microarray method at the G1/S transition
      point, 76 genes were similarly and significantly modulated in both the cell
      types, whereas another 22 genes that encompass various functional groups were
      regulated in NAD(P)H oxidase-dependent manner. Among these 22 genes, thrombin
      induced NAD(P)H oxidase-mediated regulation of Klf15, Igbp1, Ak4, Adamts5, Ech1,
      Serp1, Sec61a2, Aox1, Aoh1, Fxyd5, Rai14, and Serpinh1 was shown for the first
      time in VSMC. The role of NAD(P)H oxidase in the regulation of a subset of these
      genes (CD44, BMP4, Id1, and Id3) was confirmed using modulators of reactive
      oxygen species (ROS) generation, a ROS scavenger and in gain-of-function
      experiments. We then characterized regulation of these genes in restenosis and
      atherosclerosis. In both apoE(-/-) mice and in a mouse vascular injury model,
      these genes are regulated in NAD(P)H oxidase-dependent manner during vascular
      lesion formation. Based on these findings, we propose that NAD(P)H oxidase
      dependent gene expression in general, and the CD44 and BMP4-Id signaling pathway
      in particular, is important in restenosis and atherosclerosis.

PMID- 16601226
TI  - Gene expression profile signatures indicate a role for Wnt signaling in
      endothelial commitment from embryonic stem cells.
AB  - We have used global gene expression analysis to establish a comprehensive list of
      candidate genes in the developing vasculature during embryonic (ES) cell
      differentiation in vitro. A large set of genes, including growth factors, cell
      surface molecules, transcriptional factors, and members of several signal
      transduction pathways that are known to be involved in vasculogenesis or
      angiogenesis, were found to have expression patterns as expected. Some unknown or
      functionally uncharacterized genes were differentially regulated in flk1+ cells
      compared with flk1- cells, suggesting possible roles for these genes in vascular
      commitment. Particularly, multiple components of the Wnt signaling pathway were
      differentially regulated in flk1+ cells, including Wnt proteins, their receptors,
      downstream transcriptional factors, and other components belonging to this
      pathway. Activation of the Wnt signal was able to expand vascular progenitor
      populations whereas suppression of Wnt activity reduced flk1+ populations.
      Suppression of Wnt signaling also inhibited the formation of matured vascular
      capillary-like structures during late stages of embryoid body differentiation.
      These data indicate a requisite and ongoing role for Wnt activity during vascular
      development, and the gene expression profiles identify candidate components of
      this pathway that participate in vascular cell differentiation.

PMID- 16601227
TI  - T cell recognition and killing of vascular smooth muscle cells in acute coronary
      syndrome.
AB  - Loss of vascular smooth muscle cells (VSMCs) has been proposed to destabilize the
      atherosclerotic plaque and contribute to plaque rupture, superimposed thrombosis,
      and acute coronary syndromes (ACSs). We examined whether VSMCs are susceptible to
      T cell-induced apoptosis and found that CD4 T cells are highly effective in
      establishing cell-cell contact with VSMCs and triggering apoptotic death.
      Visualization of the T cell-VSMC contact zone on the single-cell level revealed
      that both patient-derived and control CD4 T cells reorganized their cell membrane
      to assemble an immunologic synapse with the VSMCs. Within 4 to 10 minutes, the
      membrane proximal signaling molecule ZAP-70 was recruited and phosphorylated.
      However, only patient-derived CD4 T cells sustained an intact immunologic synapse
      beyond 10 minutes and generated intracellular calcium signals. CD4 T cells that
      maintained a synaptic contact and appeared to be responsible for VSMC apoptosis
      accounted for approximately 20% of the circulating memory T cell population in
      ACS patients and were rare in the blood of age-matched controls. CD4 T cells from
      ACS patients were also hyperresponsive to T cell receptor-mediated stimulation
      when triggered by a superantigen and non-VSMC target cells. Lowered setting of
      the T cell activation threshold, attributable to excessive amplification of
      proximal CD3-mediated signals, may contribute to CD4 T cell-mediated killing of
      VSMCs and promote plaque instability.

PMID- 16601228
TI  - Caveolin plays a central role in endothelial progenitor cell mobilization and
      homing in SDF-1-driven postischemic vasculogenesis.
AB  - When neovascularization is triggered in ischemic tissues, angiogenesis but also
      (postnatal) vasculogenesis is induced, the latter requiring the mobilization of
      endothelial progenitor cells (EPC) from the bone marrow. Caveolin, the structural
      protein of caveolae, was recently reported to directly influence the angiogenic
      process through the regulation of the vascular endothelial growth factor
      (VEGF)/nitric oxide pathway. In this study, using caveolin-1 null mice (Cav(-/
      )), we examined whether caveolin was also involved in the EPC recruitment in a
      model of ischemic hindlimb. Intravenous infusion of Sca-1(+) Lin(-) progenitor
      cells, but not bone marrow transplantation, rescued the defective
      neovascularization in Cav(-/-) mice, suggesting a defect in progenitor
      mobilization. The adhesion of Cav(-/-) EPC to bone marrow stromal cells indeed
      appeared to be resistant to the otherwise mobilizing SDF-1 (Stromal cell-Derived
      Factor-1) exposure because of a defect in the internalization of the SDF-1
      cognate receptor CXCR4. Symmetrically, the attachment of Cav(-/-) EPC to SDF-1
      presenting endothelial cells was significantly increased. Finally, EPC
      transduction with caveolin small interfering RNA reproduced this advantage in
      vitro and, importantly, led to a more extensive rescue of the ischemic hindlimb
      after intravenous infusion (versus sham-transfected EPC). These results underline
      the critical role of caveolin in ensuring the caveolae-mediated endocytosis of
      CXCR4, regulating both the SDF-1-mediated mobilization and peripheral homing of
      progenitor cells in response to ischemia. In particular, a transient reduction in
      caveolin expression was shown to therapeutically increase the engraftment of
      progenitor cells.

PMID- 16601229
TI  - Abnormal interactions of calsequestrin with the ryanodine receptor calcium
      release channel complex linked to exercise-induced sudden cardiac death.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial
      arrhythmogenic disorder associated with mutations in the cardiac ryanodine
      receptor (RyR2) and cardiac calsequestrin (CASQ2) genes. Previous in vitro
      studies suggested that RyR2 and CASQ2 interact as parts of a multimolecular
      Ca(2+)-signaling complex; however, direct evidence for such interactions and
      their potential significance to myocardial function remain to be determined. We
      identified a novel CASQ2 mutation in a young female with a structurally normal
      heart and unexplained syncopal episodes. This mutation results in the
      nonconservative substitution of glutamine for arginine at amino acid 33 of CASQ2
      (R33Q). Adenoviral-mediated expression of CASQ2(R33Q) in adult rat myocytes led
      to an increase in excitation-contraction coupling gain and to more frequent
      occurrences of spontaneous propagating (Ca2+ waves) and local Ca2+ signals
      (sparks) with respect to control cells expressing wild-type CASQ2 (CASQ2WT). As
      revealed by a Ca2+ indicator entrapped inside the sarcoplasmic reticulum (SR) of
      permeabilized myocytes, the increased occurrence of spontaneous Ca2+ sparks and
      waves was associated with a dramatic decrease in intra-SR [Ca2+]. Recombinant
      CASQ2WT and CASQ2R33Q exhibited similar Ca(2+)-binding capacities in vitro;
      however, the mutant protein lacked the ability of its WT counterpart to inhibit
      RyR2 activity at low luminal [Ca2+] in planar lipid bilayers. We conclude that
      the R33Q mutation disrupts interactions of CASQ2 with the RyR2 channel complex
      and impairs regulation of RyR2 by luminal Ca2+. These results show that
      intracellular Ca2+ cycling in normal heart relies on an intricate interplay of
      CASQ2 with the proteins of the RyR2 channel complex and that disruption of these
      interactions can lead to cardiac arrhythmia.

PMID- 16601230
TI  - Endoplasmic reticulum stress gene induction and protection from
      ischemia/reperfusion injury in the hearts of transgenic mice with a tamoxifen
      regulated form of ATF6.
AB  - Ischemia/reperfusion (I/R) affects the integrity of the endoplasmic reticulum
      (ER), the site of synthesis and folding of numerous proteins. Therefore, I/R may
      activate the unfolded protein response (UPR), resulting in the induction of a
      collection of ER stress proteins, many of which are protective and function to
      resolve the ER stress. In this study, we showed that when mouse hearts were
      subjected to ex vivo I/R, the levels of 2 ER stress-inducible markers of the UPR,
      the ER-targeted cytoprotective chaperones glucose-regulated proteins 78 and 94
      (GRP78 and GRP94), were increased, consistent with I/R-mediated UPR activation in
      the heart. The UPR-mediated activation of ATF6 (Activation of Transcription
      Factor 6) induces cytoprotective ER stress proteins, including GRP78 and GRP94.
      To examine whether ATF6 protects the myocardium from I/R injury in the heart, we
      generated transgenic (TG) mice featuring cardiac-restricted expression of a novel
      tamoxifen-activated form of ATF6, ATF6-MER. When NTG and ATF6-MER TG mice were
      treated with or without tamoxifen for 5 days, only the hearts from the tamoxifen
      treated TG mice exhibited increased levels of many ER stress-inducible mRNAs and
      proteins; for example, GRP78 and GRP94 transcript levels were increased by 8- and
      15-fold, respectively. The tamoxifen-treated TG mouse hearts also exhibited
      better functional recovery from ex vivo I/R, as well as significantly reduced
      necrosis and apoptosis. These results suggest that the UPR is activated in the
      heart during I/R and that, as a result, the ATF6 branch of the UPR may induce
      expression of proteins that can function to reduce I/R injury.

PMID- 16601231
TI  - Secretory phospholipase A2 group V: lesion distribution, activation by arterial
      proteoglycans, and induction in aorta by a Western diet.
AB  - OBJECTIVE: To study the distribution of group V secretory phospholipase A2
      (sPLA2) in human and mouse lesions and compare its expression by human vascular
      cells, its activity toward lipoproteins, and the interaction with arterial
      proteoglycans (proteoglycans) with those of sPLA2-IIA. In addition, we also
      investigated the effect of a Western diet and lipopolysaccharide challenge on the
      aortic expression of these enzymes in mouse models. METHODS AND RESULTS:
      Immunohistochemistry showed sPLA2-V in human and mouse lesions to be associated
      with smooth muscle cells and also surrounding foam cells in lipid core areas.
      mRNA of the enzyme was expressed in human lesions and human vascular cells,
      supporting the immunohistochemistry data. sPLA2-V but not sPLA2-IIA was active on
      lipoproteins in human serum. The association with proteoglycans enhanced 2- to 3
      fold sPLA2-V activity toward low-density lipoproteins but not that of the group
      IIA enzyme. Experiments in mouse models showed that treatment with a Western diet
      induced expression of sPLA2-V but not that of sPLA2-IIA in aorta. On the other
      hand, lipopolysaccharide-induced acute inflammation augmented the expression of
      sPLA2-IIA but not that of sPLA2-V. CONCLUSIONS: These results indicate that these
      phospholipases could have different roles in atherosclerosis.

PMID- 16601232
TI  - AMP-activated protein kinase is involved in endothelial NO synthase activation in
      response to shear stress.
AB  - OBJECTIVE: The regulation of AMP-activated protein kinase (AMPK) is implicated in
      vascular biology because AMPK can phosphorylate endothelial NO synthase (eNOS).
      In this study, we investigate the regulation of the AMPK-eNOS pathway in vascular
      endothelial cells (ECs) by shear stress and the activation of aortic AMPK in a
      mouse model with a high level of voluntary running (High-Runner). METHODS AND
      RESULTS: By using flow channels with cultured ECs, AMPK Thr172 phosphorylation
      was increased with changes of flow rate or pulsatility. The activity of LKB1, the
      upstream kinase of AMPK, and the phosphorylation of eNOS at Ser1179 were
      concomitant with AMPK activation responding to changes in flow rate or
      pulsatility. The blockage of AMPK by a dominant-negative mutant of AMPK inhibited
      shear stress-induced eNOS Ser1179 phosphorylation and NO production. Furthermore,
      aortic AMPK activity and level of eNOS phosphorylation were significantly
      elevated in the aortas of High-Runner mice. CONCLUSIONS: Our results suggest that
      shear stress activates AMPK in ECs, which contributes to elevated eNOS activity
      and subsequent NO production. Hence, AMPK, in addition to serving as an energy
      sensor, also plays an important role in regulating vascular tone.

PMID- 16601233
TI  - Molecular mechanisms of vascular calcification: lessons learned from the aorta.
AB  - Vascular calcification increasingly afflicts our aging and dysmetabolic
      population. Once considered a passive process, it has emerged as an actively
      regulated form of calcified tissue metabolism, resembling the mineralization of
      endochondral and membranous bone. Executive cell types familiar to bone
      biologists, osteoblasts, chondrocytes, and osteoclasts, are seen in calcifying
      macrovascular specimens. Lipidaceous matrix vesicles, with biochemical and
      ultrastructural "signatures" of skeletal matrix vesicles, nucleate vascular
      mineralization in diabetes, dyslipidemia, and uremia. Skeletal morphogens (bone
      morphogenetic protein-2 (BMP) and BMP4 and Wnts) divert aortic mesoangioblasts,
      mural pericytes (calcifying vascular cells), or valve myofibroblasts to
      osteogenic fates. Paracrine signals provided by these molecules mimic the
      epithelial-mesenchymal interactions that induce skeletal development. Vascular
      expression of pro-osteogenic morphogens is entrained to physiological stimuli
      that promote calcification. Inflammation, shear, oxidative stress,
      hyperphosphatemia, and elastinolysis provide stimuli that: (1) promote vascular
      BMP2/4 signaling and matrix remodeling; and (2) compromise vascular defenses that
      limit calcium deposition, inhibit osteo/chondrogenic trans-differentiation, and
      enhance matrix vesicle clearance. In this review, we discuss the biology of
      vascular calcification. We highlight how aortic fibrofatty tissue expansion
      (adventitia, valve interstitium), the adventitial-medial vasa, vascular matrix,
      and matrix vesicle metabolism contribute to the regulation of aortic calcium
      deposition, with greatest emphasis placed on diabetic vascular disease.

PMID- 16601234
TI  - Transforming growth factor-beta-induced expression of the apolipoprotein E gene
      requires c-Jun N-terminal kinase, p38 kinase, and casein kinase 2.
AB  - OBJECTIVE: The cytokine transforming growth factor-beta (TGF-beta) and
      apolipoprotein E (apoE) play potent antiatherogenic roles. Despite such
      importance, the mechanisms underlying the regulation of apoE expression by TGF
      beta have not been characterized and were therefore investigated. METHODS AND
      RESULTS: Using THP-1 cell line as a model system, with key findings confirmed in
      primary cultures, we show that TGF-beta induces the expression of apoE, and this
      is prevented by pharmacological inhibitors of c-Jun N-terminal kinase (JNK), p38
      kinase, and casein kinase 2 (CK2). In support for an important role for these
      pathways, TGF-beta activates JNK, p38 kinase, and CK2, and dominant-negative (DN)
      forms of these proteins inhibit the cytokine-induced apoE expression. TGF-beta
      also increases the phosphorylation and expression of c-Jun, a downstream target
      for JNK action and a component of activator protein-1 (AP-1), and DN c-Jun
      inhibits the induction of apoE expression in response to the cytokine. AP-1 DNA
      binding was also induced by TGF-beta, and the action of p38 kinase, JNK, and CK2
      converged on the activation of c-Jun/AP-1. CONCLUSIONS: These studies reveal a
      novel role for JNK, p38 kinase, CK2, and c-Jun/AP-1 in the TGF-beta-induced
      expression of apoE.

PMID- 16601235
TI  - Perivascular adipose tissue and mesenteric vascular function in spontaneously
      hypertensive rats.
AB  - OBJECTIVE: Perivascular adipose tissue of normotensive rats releases a
      transferable factor that induces relaxation by opening voltage-dependent K+ (Kv)
      channels. The relevance of these observations to hypertension is unknown. METHODS
      AND RESULTS: We characterized mesenteric perivascular adipose tissue from 3-month
      old Wistar Kyoto rats (WKY) and aged-matched spontaneously hypertensive rats
      (SHR). Mesenteric bed (MB) weight and MB total lipid content were lower in SHR
      than in WKY. Freshly isolated MB adipocytes were smaller in SHR. Plasma
      triglycerides, glycerol, nonesterified free-fatty acids, and cholesterol were
      also lower in SHR. Plasma and mesenteric leptin were correlated with the quantity
      of mesenteric fat. To study vascular function, the MB was cannulated and perfused
      at a constant 2 mL/min flow. The Kv channel blocker 4-aminopyridine (4-AP; 2
      mmol/L) increased perfusion pressure less in SHR MB than WKY and was directly
      correlated with the mesenteric fat amount. In isolated mesenteric artery rings, 4
      AP (2 mmol/L) induced a contractile effect that was attenuated in SHR compared
      with WKY. The anticontractile effects of perivascular fat were reduced in SHR
      mesenteric artery rings compared with WKY. CONCLUSIONS: Differences in visceral
      perivascular adipose tissue mass and function may contribute to the increased
      vascular resistance observed in SHR.

PMID- 16601236
TI  - N-terminal proteolysis of the endothelin B receptor abolishes its ability to
      induce EGF receptor transactivation and contractile protein expression in
      vascular smooth muscle cells.
AB  - OBJECTIVE: The extracellular N terminus of the endothelin B (ETB) receptor is
      cleaved by a metalloprotease in an agonist-dependent manner, but the
      physiological role of this N-terminal proteolysis is not known. In this study, we
      aimed to determine the functional role of the ETB receptor and of its N-terminal
      cleavage in vascular smooth muscle cells (VSMCs). METHODS AND RESULTS: VSMCs
      expressing either the full-length ETB receptor or an N-terminally truncated ETB
      receptor (corresponding to the N-terminally cleaved receptor) were analyzed for
      ligand-induced mitogen-activated protein kinase activation and expression of
      contractile proteins. In VSMCs expressing the full-length ETB receptor, IRL1620
      (an ETB-selective agonist) induced a biphasic extracellular signal-regulated
      kinase 1/2 (ERK1/2) activation and increased expression of contractile proteins
      (smooth muscle myosin-1 [SM-1]/SM-2, SM22alpha, and alpha-actin). Interestingly,
      the second phase of ERK1/2 activation required metalloprotease activity,
      epidermal growth factor (EGF) receptor transactivation, and predominantly
      activation of Gi proteins. In contrast, in VSMCs expressing N-terminally
      truncated ETB receptors, IRL1620 did not elicit EGF transactivation and failed to
      increase contractile protein expression. CONCLUSIONS: This study is the first to
      show that stimulation of full-length ETB receptors promotes expression of
      contractile proteins and may thus participate in the differentiation of VSMCs.

PMID- 16601237
TI  - Biologically active CD40 ligand is elevated in sickle cell anemia: potential role
      for platelet-mediated inflammation.
AB  - OBJECTIVE: After activation, platelets expose CD40 ligand (CD40L) on their
      surface, then subsequently release the inflammatory mediator as a soluble
      fragment (sCD40L). Because sickle cell anemia (SCA) is noted for both platelet
      activation and chronic inflammation, we asked whether platelet-released CD40L
      potentially plays a role in SCA. METHODS AND RESULTS: ELISAs demonstrate that SCA
      patient plasma contains 30-fold more sCD40L than control plasma. Correspondingly,
      platelets from these patients contain less than half the CD40L found in control
      platelets. Platelets from patients in painful crises are further depleted of
      CD40L, with even higher plasma levels, suggesting a correlation to the patient's
      clinical state. In addition, elevated sCD40L correlates with increased tissue
      factor in SCA plasma. Blockage of the CD40L receptor CD40 reduces SCA plasma
      induced production of tissue factor and endothelial intercellular adhesion
      molecule-1 (ICAM-1). Finally, sCD40L activity in SCA plasma is confirmed by its
      induction of B-cell proliferation. CONCLUSIONS: Platelet-derived sCD40L is
      elevated in SCA, further elevated in crises, and biologically active. The
      participation of sCD40L in SCA plasma-induced production of B cells, tissue
      factor, and ICAM-1 suggests that CD40L may contribute to the chronic inflammation
      and increased thrombotic activity known to occur in SCA.

PMID- 16601238
TI  - Keratinocyte growth factor induces lipogenesis in alveolar type II cells through
      a sterol regulatory element binding protein-1c-dependent pathway.
AB  - Keratinocyte growth factor (KGF) stimulates fatty acid and phospholipid synthesis
      in alveolar type II cells in vitro. KGF stimulates lipogenic enzymes, including
      fatty acid synthase and stearyl-CoA desaturase-1, and transcription factors
      involved in lipogenesis, such as sterol regulatory element binding protein
      (SREBP)-1c and CCAAT/enhancer binding protein (C/EBP)alpha and C/EBPdelta. To
      define the role of SREBP-1c on the induction of lipogenic genes and lipogenesis
      by KGF in primary cultures of rat type II cells, we used adenoviral vectors to
      alter levels of SREBP-1c. Overexpression of a dominant-negative form of SREBP-1
      decreased lipogenesis and decreased the induction of fatty acid synthase and
      stearyl coenzyme A desaturase-1 by KGF. Conversely, adenovirus-mediated
      overexpression of a constitutively active form of SREBP-1c mimicked the effect of
      KGF on lipogenic enzymes and lipogenesis. These data indicate that SREBP-1c is
      required for the stimulation of lipogenesis by KGF in the alveolar type II cells
      and is a key regulator of lung lipid metabolism and that expression of SREBP-1c
      is sufficient to induce lipogenesis in rat type II cells.

PMID- 16601239
TI  - PKCalpha mediates CCL18-stimulated collagen production in pulmonary fibroblasts.
AB  - A CC chemokine, CCL18, has been previously reported to stimulate collagen
      production in pulmonary fibroblasts. This study focused on the role of protein
      kinase C (PKC) in the profibrotic signaling activated by CCL18 in pulmonary
      fibroblasts. Of the three PKC isoforms that are predominantly expressed in
      fibroblasts (PKCalpha, PKCdelta, and PKCepsilon), two isoforms (PKCdelta and
      PKCepsilon) have been implicated in profibrotic intracellular signaling. The role
      of PKCalpha-mediated signaling in the regulation of collagen production remains
      unclear. In this study, PKCalpha was found mostly in the cytoplasm, whereas
      PKCdelta and PKCepsilon were found mostly in the nucleus of cultured primary
      pulmonary fibroblasts. In response to stimulation with CCL18, PKCalpha but not
      PKCdelta or PKCepsilon underwent rapid (within 5-10 min) transient
      phosphorylation and nuclear translocation. Inhibition with dominant-negative
      mutants of PKCalpha and ERK2, but not PKCdelta or PKCepsilon, abrogated CCL18
      stimulated ERK2 phosphorylation and collagen production. The effect of CCL18 on
      collagen production and the activity of collagen promoter reporter constructs
      were also abrogated by a selective pharmacologic inhibitor of PKCalpha Go6976.
      Stimulation of fibroblasts with CCL18 caused an increase in intracellular calcium
      concentration. Consistent with the known calcium dependence of PKCalpha
      signaling, blocking of the calcium signaling with the intracellular calcium
      chelating agent BAPTA led to abrogation of PKCalpha nuclear translocation, ERK2
      phosphorylation, and collagen production. These observations suggest that in
      primary pulmonary fibroblasts, PKCalpha but not PKCdelta or PKCepsilon mediate
      the profibrotic effect of CCL18. PKCalpha may therefore become a viable target
      for future antifibrotic therapies.

PMID- 16601240
TI  - Dissection of the hyperadhesive phenotype of airway eosinophils in asthma.
AB  - Asthma is characterized by appearance of eosinophils in the airway. Eosinophils
      purified from the airway 48 h after segmental antigen challenge are described as
      exhibiting greater adhesion to albumin-coated surfaces via an unidentified beta2
      integrin and increased expression of alphaMbeta2 (CD11b/18) compared with
      purified blood eosinophils. We have investigated the determinants of this
      hyperadhesive phenotype. Airway eosinophils exhibited increased reactivity with
      the CBRM1/5 anti-alphaM activation-sensitive antibody as well as enhanced
      adhesion to VCAM-1 (CD106) and diverse ligands, including albumin, ICAM-1 (CD54),
      fibrinogen, and vitronectin. Purified blood eosinophils did not adhere to the
      latter diverse ligands. Enhanced adhesion of airway eosinophils was blocked by
      anti-alphaMbeta2. Podosomes, structures implicated in cell movement and
      proteolysis of matrix proteins, were larger and more common on airway eosinophils
      adherent to VCAM-1 when compared with blood eosinophils. Incubation of blood
      eosinophils with IL-5 replicated the phenotype of airway eosinophils. That is, IL
      5 enhanced recognition of alphaM by CBRM1/5; stimulated alphaMbeta2-mediated
      adhesion to VCAM-1, albumin, ICAM-1, fibrinogen, and vitronectin; and increased
      podosome formation on VCAM-1. Thus, the hyperadhesion of airway eosinophils after
      antigen challenge is mediated by upregulated and activated alphaMbeta2.

PMID- 16601241
TI  - Extracellular matrix remodeling by dynamic strain in a three-dimensional tissue
      engineered human airway wall model.
AB  - Airway wall remodeling is a hallmark of asthma, characterized by subepithelial
      thickening and extracellular matrix (ECM) remodeling. Mechanical stress due to
      hyperresponsive smooth muscle cells may contribute to this remodeling, but its
      relevance in a three-dimensional environment (where the ECM plays an important
      role in modulating stresses felt by cells) is unclear. To characterize the
      effects of dynamic compression in ECM remodeling in a physiologically relevant
      three-dimensional environment, a tissue-engineered human airway wall model with
      differentiated bronchial epithelial cells atop a collagen gel containing lung
      fibroblasts was used. Lateral compressive strain of 10 or 30% at 1 or 60 cycles
      per hour was applied using a novel straining device. ECM remodeling was assessed
      by immunohistochemistry and zymography. Dynamic strain, particularly at the lower
      magnitude, induced airway wall remodeling, as indicated by increased deposition
      of types III and IV collagen and increased secretion of matrix metalloproteinase
      2 and -9. These changes paralleled increased myofibroblast differentiation and
      were fibroblast-dependent. Furthermore, the spatial pattern of type III collagen
      deposition correlated with that of myofibroblasts; both were concentrated near
      the epithelium and decreased diffusely away from the surface, indicating some
      epithelial control of the remodeling response. Thus, in a physiologically
      relevant three-dimensional model of the bronchial wall, dynamic compressive
      strain induced tissue remodeling that mimics many features of remodeling seen in
      asthma, in the absence of inflammation and dependent on epithelial-fibroblast
      signaling.

PMID- 16601242
TI  - Cigarette smoke-induced Egr-1 upregulates proinflammatory cytokines in pulmonary
      epithelial cells.
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death
      worldwide and is a progressive and irreversible disorder. Cigarette smoking is
      associated with 80-90% of COPD cases; however, the genes involved in COPD
      associated emphysema and chronic inflammation are poorly understood. It was
      recently demonstrated that early growth response gene 1 (Egr-1) is significantly
      upregulated in the lungs of smokers with COPD (Ning W and coworkers, Proc Natl
      Acad Sci 2004;101:14895-14900). We hypothesized that Egr-1 is activated in
      pulmonary epithelial cells during exposure to cigarette smoke extract (CSE).
      Using immunohistochemistry, we demonstrated that pulmonary adenocarcinoma cells
      (A-549) and primary epithelial cells lacking basal Egr-1 markedly induce Egr-1
      expression after CSE exposure. To evaluate Egr-1-specific effects, we used
      antisense (alphaS) oligodeoxynucleotides (ODN) to knock down Egr-1 expression.
      Incorporation of Egr-1 alphaS ODN significantly decreased CSE-induced Egr-1 mRNA
      and protein, while sense ODN had no effect. Via Egr-1-mediated mechanisms, IL
      1beta and TNF-alpha were significantly upregulated in pulmonary epithelial cells
      exposed to CSE or transfected with Egr-1. To investigate the relationship between
      Egr-1 induction by smoking and susceptibility to emphysema, we determined Egr-1
      expression in strains of mice with different susceptibilities for the development
      of smoking-induced emphysema. Egr-1 was markedly increased in the lungs of
      emphysema-susceptible AKR/J mice chronically exposed to cigarette smoke, but only
      minimally increased in resistant NZWLac/J mice. In conclusion, Egr-1 is induced
      by cigarette smoke and functions in proinflammatory mechanisms that likely
      contribute to the development of COPD in the lungs of smokers.

PMID- 16601243
TI  - The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory
      responses of human mononuclear cells induced by microbial stimulation.
AB  - Microarray--assisted gene--expression screens of human macrophages revealed
      WNT5A, a homolog of Wingless, a key regulator of Drosophila melanogaster
      embryonic segmentation and patterning, to be consistently up-regulated following
      stimulation with different mycobacterial species and conserved bacterial
      structures. The expression of WNT5A required Toll-like receptor signaling and NF
      kappaB activation, which identifies a novel induction pathway for a Wingless
      homolog. We show that human peripheral-blood mononuclear cells express the WNT5A
      receptor Frizzled-5 (FZD5). Both WNT5A and FZD5 also were detected in
      granulomatous lesions in the lungs of Mycobacterium tuberculosis-infected
      patients. Functional studies showed that WNT5A and FZD5 regulate the microbially
      induced interleukin-12 response of antigen-presenting cells and interferon-gamma
      production by mycobacterial antigen-stimulated T cells. Our findings implicate
      the evolutionarily conserved WNT/Frizzled signaling system in bridging innate and
      adaptive immunity to infections.

PMID- 16601244
TI  - Clinical significance of ZAP-70 protein expression in B-cell chronic lymphocytic
      leukemia.
AB  - The clinical course of B-cell chronic lymphocytic leukemia (B-CLL) is variable,
      and novel biologic parameters need to be added to the clinical staging systems to
      predict an indolent or aggressive outcome. We investigated the 70-kDa zeta
      associated protein (ZAP-70), CD38, soluble CD23 (sCD23), and cytogenetics in 289
      patients with B-CLL. Both a shorter progression-free survival (PFS) and overall
      survival (OS) were observed in ZAP-70(+) (P < .001), in CD38(+) (P < .001) and in
      sCD23(+) patients (P < .001 and P = .013, respectively). ZAP-70(+)CD38(+) or ZAP
      70(+) patients with an unmutated IgV(H) status showed both a shorter PFS (P <
      .001) and OS (P < .001 and P < .001, respectively) as compared with ZAP-70(
      )/CD38(-) or ZAP-70(-) patients with mutated IgV(H) genes. Discordant patients
      showed an intermediate outcome. Note, ZAP-70(+) patients even if CD38(-) or
      mutated showed a shorter PFS, whereas ZAP-70(-) patients even if CD38(+) or
      unmutated had a longer PFS. Furthermore, ZAP-70 positivity was associated with a
      shorter PFS both within normal karyotype (P < .001) and within the poor-risk
      cytogenetic subset (P = .02). The predictive value of ZAP-70 expression was
      confirmed in multivariate analysis. Thus, ZAP-70 protein determined by flow
      cytometry improves the prognostic significance of cytogenetics and appears to be
      a better predictor of outcomes than IgV(H) gene mutational status. On this line,
      we recommend and are also interested in conducting a prospective randomized trial
      of early intervention versus observation for ZAP-70(+) patients.

PMID- 16601245
TI  - Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells.
AB  - The transmembrane ubiquitin ligase K5/MIR2 of Kaposi sarcoma herpesvirus (KSHV)
      mediates internalization and lysosomal degradation of glycoproteins involved in
      antigen presentation and co-stimulation. In endothelial cells (ECs), K5
      additionally reduced expression of CD31/platelet-endothelial cell adhesion
      molecule (PECAM), an adhesion molecule regulating cell-cell interactions of ECs,
      platelets, monocytes, and T cells. K5 also reduced EC migration, a CD31-dependent
      process. Unlike other K5 substrates, both newly synthesized and pre-existing CD31
      molecules were targeted by K5. K5 was transported to the cell surface and
      ubiquitinated pre-existing CD31, resulting in endocytosis and lysosomal
      degradation. In the endoplasmic reticulum, newly synthesized CD31 was degraded by
      proteasomes, which required binding of phosphofurin acidic cluster sorting
      protein-2 (PACS-2) to acidic residues in the carboxyterminal tail of K5. Thus,
      CD31, a novel target of K5, is efficiently removed from ECs by a dual degradation
      mechanism that is regulated by the subcellular sorting of the ubiquitin ligase.
      K5-mediated degradation of CD31 is likely to affect EC function in KS tumors.

PMID- 16601247
TI  - Allogeneic stem cell transplantation for patients with chronic myeloid leukemia
      and acute lymphocytic leukemia after Bcr-Abl kinase mutation-related imatinib
      failure.
AB  - Resistance to imatinib mesylate is an emerging problem in the treatment of
      chronic myeloid leukemia (CML), often associated with point mutations in the Bcr
      Abl kinase domain. Outcome of patients with such mutations after allogeneic stem
      cell transplantation (Allo-SCT) is unknown. Ten imatinib-resistant patients with
      Bcr-Abl kinase mutations received a transplant: 9 had CML (3 in chronic phase, 4
      in accelerated phase, and 2 in blast phase) and 1 had Philadelphia-positive acute
      lymphocytic leukemia (ALL). Patients harbored 9 different protein kinase
      mutations (T315I mutation, n = 2). Preparative regimens were ablative (n = 7) and
      nonablative (n = 3). All patients engrafted; there were no treatment-related
      deaths. Disease response was complete molecular (CMR; n = 7), major molecular (n
      = 2), and no response (n = 1). Three patients (mutations Q252H, E255K, and T315I)
      died of relapse after Allo-SCT. Seven patients are alive (6 in CMR) for a median
      of 19 months. Allo-SCT remains an important salvage option for patients who
      develop resistance to imatinib through Bcr-Abl mutations.

PMID- 16601254
TI  - Redesigning training for internal medicine.
AB  - The American College of Physicians supports the need for reform throughout the
      continuum of training in internal medicine. Today's internists must have the
      necessary knowledge, skills, and attitudes to meet the challenges of an expanding
      body of medical knowledge and a rapidly evolving system of health care delivery.
      Suggested priorities for undergraduate medical education include redesigning
      curricular experiences to afford students earlier and more exposure to career
      opportunities in internal medicine, improving ambulatory education, exposing
      students to outstanding faculty role models in internal medicine, and
      incorporating educational experiences during the fourth year that optimize its
      value and relevance to the student's future career plans in internal medicine.
      Internal medicine residency training should remain a 3-year experience, with a
      component of core education common to all trainees and a component of customized
      training in the third year targeted toward the resident's career goals. Residency
      programs should be designed around educational rather than institutional service
      needs. The ambulatory component of training requires substantial reform in its
      structure, sites, content, and timing. Team-based models should be used both for
      patient care and for flexibility in design of residency training. Better faculty
      models must be developed that build on the concept of a "core faculty," improve
      the rewards for teaching faculty, and provide appropriate faculty development
      focusing on a necessary set of educator competencies.

PMID- 16601255
TI  - Peer victimization, psychosocial adjustment, and physical activity in overweight
      and at-risk-for-overweight youth.
AB  - OBJECTIVE: To examine the relationship between peer victimization and child and
      parent reports of psychosocial adjustment and physical activity in a clinical
      sample of at-risk-for-overweight and overweight children and adolescents.
      METHODS: The Schwartz Peer Victimization Scale, Children's Depression Inventory
      Short Form, Multidimensional Anxiety Scale for Children, Social Physique Anxiety
      Scale, PACE+ Adolescent Physical Activity Measure, and Asher Loneliness Scale
      were administered to 92 children and adolescents (54 females) aged 8-18 years.
      The youth's parent/guardian completed the Child Behavior Checklist. RESULTS: Peer
      victimization was positively related to child-reported depression, anxiety,
      social physique anxiety, and loneliness, and parent-reported internalizing and
      externalizing symptoms. Peer victimization was negatively related to physical
      activity. Depressive symptoms and loneliness mediated the relations between peer
      victimization and physical activity. CONCLUSION: Recognition of the magnitude of
      the problem and the means of evaluating for peer victimization is important for
      clinicians who work with overweight youth. Assessing peer experiences may assist
      in understanding rates of physical activity and/or past nonadherence to clinician
      recommendations.

PMID- 16601256
TI  - Sex differences in the effects of amiloride on formalin test nociception in mice.
AB  - Amiloride is a nonspecific blocker of acid-sensing ion channels (ASICs) that have
      been recently implicated in the mediation of mechanical and chemical/inflammatory
      nociception. Preliminary data using a transgenic model are suggestive of sex
      differences in the role of ASICs. We report here that systemic administration of
      amiloride (10-70 mg/kg ip) produces a robust, dose-dependent blockade of
      late/tonic phase nociceptive behavior on the mouse formalin test (5%; 20 microl)
      in female but not male mice, completely abolishing the known sex difference in
      formalin test response. Adult gonadectomy produced a "switching" of sex
      differences in amiloride efficacy, with castrated males displaying an amiloride
      blockade and ovariectomized females rendered less sensitive to amiloride.
      Gonadectomized mice could be switched back to their intact status using chronic
      estrogen benzoate or testosterone propionate replacement via osmotic minipump (6
      microg/day or 250 microg/day, respectively). It is unclear whether this striking
      sex difference is due to sex-specific involvement of ASICs in pain processing,
      but the present data represent one of the first demonstrations of pain-related
      sex differences with no obvious opioid involvement.

PMID- 16601257
TI  - Comparison between two rat sympathetic pathways activated in cold defense.
AB  - In cold defense and fever, activity increases in sympathetic nerves supplying
      both tail vessels and interscapular brown adipose tissue (iBAT). These mediate
      cutaneous vasoconstrictor and thermogenic responses, respectively, and both
      depend upon neurons in the rostral medullary raphe. To examine the commonality of
      brain circuits driving these two outflows, sympathetic nerve activity (SNA) was
      recorded simultaneously from sympathetic fibers in the ventral tail artery (tail
      SNA) and the nerve to iBAT (iBAT SNA) in urethane-anesthetized rats. From a warm
      baseline, cold-defense responses were evoked by intermittently circulating cold
      water through a water jacket around the animal's shaved trunk. Repeated episodes
      of trunk skin cooling decreased core (rectal) temperature. The threshold skin
      temperature to activate iBAT SNA was 37.3 +/- 0.5 degrees C (n = 7),
      significantly lower than that to activate tail SNA (40.1 +/- 0.4 degrees C; P <
      0.01, n = 7). A fall in core temperature always strongly activated tail SNA
      (threshold 38.3 +/- 0.2 degrees C, n = 7), but its effect on iBAT SNA was absent
      (2 of 7 rats) or weak (threshold 36.9 +/- 0.1 degrees C, n = 5). The relative
      sensitivity to core vs. skin cooling (K-ratio) was significantly greater for tail
      SNA than for iBAT SNA. Spectral analysis of paired recordings showed significant
      coherence between tail SNA and iBAT SNA only at 1.0 +/- 0.1 Hz. The coherence was
      due entirely to the modulation of both signals by the ventilatory cycle because
      it disappeared when the coherence spectrum was partialized with respect to airway
      pressure. These findings indicate that independent central pathways drive
      cutaneous vasoconstrictor and thermogenic sympathetic pathways during cold
      defense.

PMID- 16601258
TI  - NMDA receptor antagonism disrupts the development of morphine analgesic tolerance
      in male, but not female C57BL/6J mice.
AB  - Multiple studies demonstrate that coadministration of N-methyl-D-aspartate (NMDA)
      receptor antagonists with the opioid agonist morphine attenuates the development
      of analgesic tolerance. Sex differences in the effects of noncompetitive, but not
      competitive NMDA receptor antagonists on acute morphine analgesia, have been
      reported in mice, yet the role of sex in modulation of morphine tolerance by NMDA
      receptor antagonists has yet to be addressed. Therefore, we tested whether there
      is a sex difference in the effect of NMDA receptor antagonists on the development
      of morphine analgesic tolerance in C57BL/6J mice. Acutely, at a dose required to
      affect morphine tolerance in male mice, the noncompetitive NMDA receptor
      antagonist dizocilpine (MK-801) prolonged morphine analgesia similarly in both
      sexes in the hot plate and tail withdrawal assays. In the hot plate assay,
      coadministration of MK-801 or the competitive antagonist 3-(2-carboxpiperazin-4
      yl)propyl-1-phosphanoic acid (CPP) with morphine attenuated the development of
      tolerance in male mice, while having no effect in females. Like normal and sham
      females, ovariectomized mice were similarly insensitive to the attenuation of
      morphine tolerance by MK-801 in the hot plate assay. Surprisingly, in the tail
      withdrawal assay, MK-801 facilitated the development of morphine-induced
      hyperalgesia and tolerance in males but not females. The results demonstrate that
      male mice are more sensitive to modulation of nociception and morphine analgesia
      after repeated coadministration of NMDA receptor antagonists. Furthermore, the
      underlying mechanisms are likely to be different from those mediating the sex
      difference in the modulation of acute morphine analgesia that has previously been
      reported.

PMID- 16601259
TI  - Central angiotensin II receptors mediate hemodynamic response variability to
      stressors.
AB  - We examined whether ANG II receptors in the central nervous system mediate
      hemodynamic responses to pharmacological (cocaine) and behavioral (cold water)
      stressors. After administration of cocaine (5 mg/kg iv), rats were classified as
      vascular responders (VR) if their pressor response was due entirely to an
      increase in systemic vascular resistance (SVR) despite a decrease in cardiac
      output (CO). Cocaine elicited a pressor response in mixed responders (MR) that
      was dependent on small increases in both SVR and CO. ANG II (30 ng/5 microl icv,
      5 min before cocaine) augmented the decrease in CO in VR and prevented the
      increase in CO in MR. Administration of [Sar(1),Thr(8)]ANG II (20 microg/5 microl
      icv; sarthran) before cocaine attenuated the decrease in CO and the large
      increase in SVR in VR so that they were no longer different from MR. Losartan (20
      microg icv) or captopril (50 microg icv) preceding cocaine administration also
      attenuated the decrease in CO and the large increase in SVR seen in VR only. The
      role of angiotensin was not specific for cocaine, because ANG II (icv)
      pretreatment before startle with cold water (1 cm deep) enhanced the decrease in
      CO and the increase in SVR in both MR and VR, whereas losartan (icv) pretreatment
      before startle attenuated the decrease in CO and the increase in SVR in VR so
      that they were no longer different from MR. These data suggest that central ANG
      II receptors mediate the greater vascular and cardiac responsiveness in vascular
      responders to acute pharmacological and behavioral stressors.

PMID- 16601260
TI  - Photoperiodic regulation of insulin receptor mRNA and intracellular insulin
      signaling in the arcuate nucleus of the Siberian hamster, Phodopus sungorus.
AB  - During the last 5 years it has been well established that photoperiod-induced
      changes in body weight in the seasonal hamster, Phodopus sungorus, are
      accompanied by a marked seasonal cycle in leptin sensitivity. In the present
      study, we investigated the possible involvement of insulin signaling in seasonal
      body weight regulation. We analyzed the expression pattern and relative intensity
      of insulin receptor (IR), phosphatidylinositol 3-kinase (PI3-kinase), and protein
      tyrosine phosphatase 1B (PTP1B) mRNAs by in situ hybridization in the brains of
      juvenile female hamsters acclimated to either long- (LD) or short-day length (SD)
      for 8 wk, with or without superimposed food deprivation for 48 h. Furthermore,
      the hypothalamic concentration and distribution of phospho-AKT, a marker of PI3
      kinase activity was determined by immunoblotting and immunohistochemistry. Eight
      weeks of acclimation to SD led to a substantial downregulation of IR, PTP1B gene
      expression, and phospho-AKT concentration in this brain region, whereas PI3
      kinase mRNA was unchanged. Food deprivation induced a decrease in PTP1B and a
      trend toward lowered IR gene expression in LD but not in SD. Additionally, a
      striking increase in PTP1B gene expression in the thalamus was observed after
      food deprivation in both photoperiods. The direction of change in neuronal
      insulin signaling contrasts to the central catabolic nature of this pathway
      described in other species. SD-induced reduction in insulin signaling may be due
      to decline in body fat stores mediated by enhanced central leptin sensitivity.
      Increased anorexigenic tone of leptin may overwrite central insulin signaling to
      prevent catabolic overdrive.

PMID- 16601262
TI  - Nitric oxide modulates elicitation of reflex swallowing from the pharynx in rats.
AB  - The pharynx is very important for elicitation of reflex swallowing. The region of
      the pharynx is innervated by the pharyngeal branch of the glossopharyngeal nerve
      (GPN-ph). Nitric oxide (NO) plays an important role in various physiological
      functions. The purpose of this study is to investigate the contribution of NO to
      reflex swallowing evoked by electrical stimulation of the GPN-ph. Swallowing was
      evoked in urethane-anesthetized rats by application of repetitive electrical
      stimulation (10- to 20-microA amplitude, 10- to 20-Hz frequency, 1.0-ms duration)
      to the central cut end of the GPN-ph or superior laryngeal nerve. Swallowing was
      identified by electromyographic activity of the mylohyoid muscle. Latency to the
      first swallow and the interval between swallows were measured. Intravenous
      administration of N(G)-nitro-L-arginine (L-NNA, 0.6 mg/kg), a nonselective
      inhibitor of NO synthase (NOS), extremely prolonged latency to the first swallow
      and the interval between swallows evoked by the GPN-ph. Intraperitoneal
      administration of 7-nitroindazole (5.0 mg/kg), a selective inhibitor of neuronal
      NOS, significantly prolonged latency to the first swallow and the interval
      between swallows evoked by the GPN-ph. Administration of L-arginine (an NO donor,
      500 mg/kg) and sodium nitroprusside (an NO releaser, 0.6 mg/kg) restored the
      suppression of swallowing induced by the NOS inhibitor. Superior laryngeal nerve
      evoked swallowing was suppressed by administration of a higher dose of L-NNA (6.0
      mg/kg). Swallowing evoked by water stimulation of the pharynx was also suppressed
      by L-NNA (0.6 mg/kg). These results suggest that NO plays an important role in
      signal processing for initiation of reflex swallowing from the pharynx.

PMID- 16601261
TI  - Contribution of adenosine A2A and A2B receptors and heme oxygenase to AMPA
      induced dilation of pial arterioles in rats.
AB  - Nitric oxide (NO) has been implicated in mediation of cerebral vasodilation
      during neuronal activation and, specifically, in pharmacological activation of N
      methyl-d-aspartate (NMDA) and kainate receptors. Possible mediators of cerebral
      vasodilation to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      have not been well studied in mature brain, although heme oxygenase (HO) activity
      has been implicated in newborn pigs. In anesthetized rats, 5 min of topical
      superfusion of 30 and 100 microM AMPA on the cortical surface through a closed
      cranial window resulted in increases in pial arteriolar diameter. The dilatory
      response to AMPA was not inhibited by superfusion of an NO synthase inhibitor, a
      cyclooxygenase-2 inhibitor, or a cytochrome P-450 epoxygenase inhibitor, all of
      which have been shown to inhibit the cortical blood flow response to sensory
      activation. However, the 48 +/- 13% dilation to 100 microM AMPA was attenuated 56
      71% by superfusion of the adenosine A(2A) receptor antagonist ZM-241385, the
      A(2B) receptor antagonist alloxazine, and the HO inhibitor chromium
      mesoporphyrin. Combination of the latter three inhibitors did not attenuate the
      dilator response more than the individual inhibitors, whereas an AMPA receptor
      antagonist fully blocked the vasodilation to AMPA. These results indicate that
      cortical pial arteriolar dilation to AMPA does not require activation of NO
      synthase, cyclooxygenase-2, or cytochrome P-450 epoxygenase but does depend on
      activation of adenosine A(2A) and A(2B) receptors. In addition, CO derived from
      HO appears to play a role in the vascular response to AMPA receptor activation in
      mature brain by a mechanism that is not additive with that of adenosine receptor
      activation.

PMID- 16601263
TI  - Immunomodulation by 17beta-estradiol in bivalve hemocytes.
AB  - In mammals, estrogens have dose- and cell-type-specific effects on immune cells
      and may act as pro- and anti-inflammatory stimuli, depending on the setting. In
      the bivalve mollusc Mytilus, the natural estrogen 17beta-estradiol (E(2)) has
      been shown to affect neuroimmune functions. We have investigated the
      immunomodulatory role of E(2) in Mytilus hemocytes, the cells responsible for the
      innate immune response. E(2) at 5-25 nM rapidly stimulated phagocytosis and
      oxyradical production in vitro; higher concentrations of E(2) inhibited
      phagocytosis. E(2)-induced oxidative burst was prevented by the nitric oxide (NO)
      synthase inhibitor N(G)-monomethyl-L-arginine and superoxide dismutase,
      indicating involvement of NO and O(2)(-); NO production was confirmed by nitrite
      accumulation. The effects of E(2) were prevented by the antiestrogen tamoxifen
      and by specific kinase inhibitors, indicating a receptor-mediated mechanism and
      involvement of p38 MAPK and PKC. E(2) induced rapid and transient increases in
      the phosphorylation state of PKC, as well as of a aCREB-like (cAMP responsive
      element binding protein) transcription factor, as indicated by Western blot
      analysis with specific anti-phospho-antibodies. Localization of estrogen receptor
      alpha- and -beta-like proteins in hemocytes was investigated by
      immunofluorescence confocal microscopy. The effects of E(2) on immune function
      were also investigated in vivo at 6 and 24 h in hemocytes of E(2)-injected
      mussels. E(2) significantly affected hemocyte lysosomal membrane stability,
      phagocytosis, and extracellular release of hydrolytic enzymes: lower
      concentrations of E(2) resulted in immunostimulation, and higher concentrations
      were inhibitory. Our data indicate that the physiological role of E(2) in
      immunomodulation is conserved from invertebrates to mammals.

PMID- 16601264
TI  - Sex differences in the cerebral BOLD signal response to painful heat stimuli.
AB  - There are limited data addressing the question of sex differences in pain-related
      cerebral processing. This study examined whether pain-related blood oxygenation
      level-dependent (BOLD) signal change measured with functional magnetic resonance
      imaging (fMRI) demonstrated sex differences, under conditions of equivalent pain
      perception. Twenty-eight healthy volunteers (17 women, 11 men) were subject to a
      fMRI scan while noxious heat stimuli were applied to the dorsum of the left foot.
      Significant BOLD signal modulation was observed in several nociceptive processing
      regions of interest (ROIs) in all subjects. There were no sex differences in the
      spatial extent of BOLD signal change for any ROI, but the signal amplitude was
      lower for women in most ROIs and significantly so for the primary somatosensory
      cortex (S1), the midanterior cingulate cortex, and the dorsolateral prefrontal
      cortex (DLPFC). The BOLD signal response could be positive or negative, and
      frequently, both polarities were observed within a single ROI. In most ROIs,
      women show proportionately more voxels with negative signal change than men, and
      this difference was statistically significant for the S1 and the DLPFC. The time
      course of the negative signal change was very similar to that of the positive
      signal change, suggesting that the latter was not "driving" the former. The
      location of negative and positive clusters formed distinct patterns in several of
      the ROIs, and these patterns suggest something other than a local "steal"
      phenomenon as an explanation for the negative signal changes. Sex differences in
      baseline cerebral blood flow may contribute to the BOLD signal differences
      observed in this study.

PMID- 16601265
TI  - Maps of odorant molecular features in the Mammalian olfactory bulb.
AB  - The olfactory bulb (OB) is the first relay station of the central olfactory
      system in the mammalian brain and contains a few thousand glomeruli on its
      surface. Because individual glomeruli represent a single odorant receptor, the
      glomerular sheet of the OB forms odorant receptor maps. This review summarizes
      the emerging view of the spatial organization of the odorant receptor maps.
      Recent studies suggest that individual odorant receptors are molecular-feature
      detecting units, and so are individual glomeruli in the OB. How are the molecular
      feature detecting units spatially arranged in the glomerular sheet? To
      characterize the molecular-feature specificity of an individual glomerulus, it is
      necessary to determine the molecular receptive range (MRR) of the glomerulus and
      to compare the molecular structure of odorants within the MRR. Studies of the MRR
      mapping show that 1) individual glomeruli typically respond to a range of
      odorants that share a specific combination of molecular features, 2) each
      glomerulus appears to be unique in its MRR property, and 3) glomeruli with
      similar MRR properties gather together in proximity and form molecular-feature
      clusters. The molecular-feature clusters are located at stereotypical positions
      in the OB and might be part of the neural representation of basic odor quality.
      Detailed studies suggest that the glomerular sheet represents the characteristic
      molecular features in a systematic, gradual, and multidimensional fashion. The
      molecular-feature maps provide a basis for understanding how the olfactory cortex
      reads the odor maps of the OB.

PMID- 16601266
TI  - Thermogenic mechanisms and their hormonal regulation.
AB  - Increased heat generation from biological processes is inherent to homeothermy.
      Homeothermic species produce more heat from sustaining a more active metabolism
      as well as from reducing fuel efficiency. This article reviews the mechanisms
      used by homeothermic species to generate more heat and their regulation largely
      by thyroid hormone (TH) and the sympathetic nervous system (SNS). Thermogenic
      mechanisms antecede homeothermy, but in homeothermic species they are activated
      and regulated. Some of these mechanisms increase ATP utilization (same amount of
      heat per ATP), whereas others increase the heat resulting from aerobic ATP
      synthesis (more heat per ATP). Among the former, ATP utilization in the
      maintenance of ionic gradient through membranes seems quantitatively more
      important, particularly in birds. Regulated reduction of the proton-motive force
      to produce heat, originally believed specific to brown adipose tissue, is indeed
      an ancient thermogenic mechanism. A regulated proton leak has been described in
      the mitochondria of several tissues, but its precise mechanism remains undefined.
      This leak is more active in homeothermic species and is regulated by TH,
      explaining a significant fraction of its thermogenic effect. Homeothermic species
      generate additional heat, in a facultative manner, when obligatory thermogenesis
      and heat-saving mechanisms become limiting. Facultative thermogenesis is
      activated by the SNS but is modulated by TH. The type II iodothyronine deiodinase
      plays a critical role in modulating the amount of the active TH, T(3), in BAT,
      thereby modulating the responses to SNS. Other hormones affect thermogenesis in
      an indirect or permissive manner, providing fuel and modulating thermogenesis
      depending on food availability, but they do not seem to have a primary role in
      temperature homeostasis. Thermogenesis has a very high energy cost. Cold
      adaptation and food availability may have been conflicting selection pressures
      accounting for the variability of thermogenesis in humans.

PMID- 16601267
TI  - Transcriptional regulation of metabolism.
AB  - Our understanding of metabolism is undergoing a dramatic shift. Indeed, the
      efforts made towards elucidating the mechanisms controlling the major regulatory
      pathways are now being rewarded. At the molecular level, the crucial role of
      transcription factors is particularly well-illustrated by the link between
      alterations of their functions and the occurrence of major metabolic diseases. In
      addition, the possibility of manipulating the ligand-dependent activity of some
      of these transcription factors makes them attractive as therapeutic targets. The
      aim of this review is to summarize recent knowledge on the transcriptional
      control of metabolic homeostasis. We first review data on the transcriptional
      regulation of the intermediary metabolism, i.e., glucose, amino acid, lipid, and
      cholesterol metabolism. Then, we analyze how transcription factors integrate
      signals from various pathways to ensure homeostasis. One example of this
      coordination is the daily adaptation to the circadian fasting and feeding rhythm.
      This section also discusses the dysregulations causing the metabolic syndrome,
      which reveals the intricate nature of glucose and lipid metabolism and the role
      of the transcription factor PPARgamma in orchestrating this association. Finally,
      we discuss the molecular mechanisms underlying metabolic regulations, which
      provide new opportunities for treating complex metabolic disorders.

PMID- 16601268
TI  - Cytokines in atherosclerosis: pathogenic and regulatory pathways.
AB  - Atherosclerosis is a chronic disease of the arterial wall where both innate and
      adaptive immunoinflammatory mechanisms are involved. Inflammation is central at
      all stages of atherosclerosis. It is implicated in the formation of early fatty
      streaks, when the endothelium is activated and expresses chemokines and adhesion
      molecules leading to monocyte/lymphocyte recruitment and infiltration into the
      subendothelium. It also acts at the onset of adverse clinical vascular events,
      when activated cells within the plaque secrete matrix proteases that degrade
      extracellular matrix proteins and weaken the fibrous cap, leading to rupture and
      thrombus formation. Cells involved in the atherosclerotic process secrete and are
      activated by soluble factors, known as cytokines. Important recent advances in
      the comprehension of the mechanisms of atherosclerosis provided evidence that the
      immunoinflammatory response in atherosclerosis is modulated by regulatory
      pathways, in which the two anti-inflammatory cytokines interleukin-10 and
      transforming growth factor-beta play a critical role. The purpose of this review
      is to bring together the current information concerning the role of cytokines in
      the development, progression, and complications of atherosclerosis. Specific
      emphasis is placed on the contribution of pro- and anti-inflammatory cytokines to
      pathogenic (innate and adaptive) and regulatory immunity in the context of
      atherosclerosis. Based on our current knowledge of the role of cytokines in
      atherosclerosis, we propose some novel therapeutic strategies to combat this
      disease. In addition, we discuss the potential of circulating cytokine levels as
      biomarkers of coronary artery disease.

PMID- 16601269
TI  - Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.
AB  - The heme oxygenases, which consist of constitutive and inducible isozymes (HO-1,
      HO-2), catalyze the rate-limiting step in the metabolic conversion of heme to the
      bile pigments (i.e., biliverdin and bilirubin) and thus constitute a major
      intracellular source of iron and carbon monoxide (CO). In recent years,
      endogenously produced CO has been shown to possess intriguing signaling
      properties affecting numerous critical cellular functions including but not
      limited to inflammation, cellular proliferation, and apoptotic cell death. The
      era of gaseous molecules in biomedical research and human diseases initiated with
      the discovery that the endothelial cell-derived relaxing factor was identical to
      the gaseous molecule nitric oxide (NO). The discovery that endogenously produced
      gaseous molecules such as NO and now CO can impart potent physiological and
      biological effector functions truly represented a paradigm shift and unraveled
      new avenues of intense investigations. This review covers the molecular and
      biochemical characterization of HOs, with a discussion on the mechanisms of
      signal transduction and gene regulation that mediate the induction of HO-1 by
      environmental stress. Furthermore, the current understanding of the functional
      significance of HO shall be discussed from the perspective of each of the
      metabolic by-products, with a special emphasis on CO. Finally, this presentation
      aspires to lay a foundation for potential future clinical applications of these
      systems.

PMID- 16601270
TI  - Nutrition and aging: changes in the regulation of energy metabolism with aging.
AB  - Changes in energy regulation occur during normal aging and contribute to the
      common phenomenon of weight and fat losses late in life. This review synthesizes
      data on aging-related changes in energy intake and energy expenditure and on the
      regulation of energy intake and expenditure. The ability of older adults to
      accurately regulate energy intake is impaired, with a number of possible
      explanations including delayed rate of absorption of macronutrients secondary to
      reductions in taste and smell acuity and numerous hormonal and metabolic
      mediators of energy regulation that change with aging. There are also changes in
      patterns of dietary intake and a reduction in the variety of foods consumed in
      old age that are thought to further reduce energy intake. Additionally, all
      components of energy expenditure decrease with aging, in particular energy
      expenditure for physical activity and basal metabolic rate, and the ability of
      energy expenditure to increase or decrease to attenuate energy imbalance during
      overeating or undereating also decreases. Combined, these changes result in an
      increased susceptibility to energy imbalance (both positive and negative) in old
      age that is associated with deteriorations in health. Practical interventions for
      prevention of weight and fat fluctuations in old age are anticipated here based
      on emerging knowledge of the role of such factors as dietary variety, taste, and
      palatability in late-life energy regulation.

PMID- 16601271
TI  - Role of ubiquitylation in cellular membrane transport.
AB  - Ubiquitylation of membrane proteins has gained considerable interest in recent
      years. It has been recognized as a signal that negatively regulates the cell
      surface expression of many plasma membrane proteins both in yeast and in
      mammalian cells. Moreover, it is also involved in endoplasmic reticulum
      associated degradation of membrane proteins, and it acts as a sorting signal both
      in the secretory pathway and in endosomes, where it targets proteins into
      multivesicular bodies in the lumen of vacuoles/lysosomes. In this review we
      discuss the progress in understanding these processes, achieved during the past
      several years.

PMID- 16601272
TI  - Hypertension, kidney, and transgenics: a fresh perspective.
AB  - In this review, we outline the application and contribution of transgenic
      technology to establishing the genetic basis of blood pressure regulation and its
      dysfunction. Apart from a small number of examples where high blood pressure is
      the result of single gene mutation, essential hypertension is the sum of
      interactions between multiple environmental and genetic factors. Candidate genes
      can be identified by a variety of means including linkage analysis, quantitative
      trait locus analysis, association studies, and genome-wide scans. To test the
      validity of candidate genes, it is valuable to model hypertension in laboratory
      animals. Animal models generated through selective breeding strategies are often
      complex, and the underlying mechanism of hypertension is not clear. A
      complementary strategy has been the use of transgenic technology. Here one gene
      can be selectively, tissue specifically, or developmentally overexpressed,
      knocked down, or knocked out. Although resulting phenotypes may still be
      complicated, the underlying genetic perturbation is a starting point for
      identifying interactions that lead to hypertension. We recognize that the
      development and maintenance of hypertension may involve many systems including
      the vascular, cardiac, and central nervous systems. However, given the central
      role of the kidney in normal and abnormal blood pressure regulation, we intend to
      limit our review to models with a broadly renal perspective.

PMID- 16601275
TI  - Epidermal growth factor receptor tyrosine kinase inhibitors and bone metastases:
      different mechanisms of action for a novel therapeutic application?
AB  - The paper by Angelucci et al. published in the current issue of Endocrine-Related
      Cancer suggests a potential, novel application of epidermal growth factor
      receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of bone
      metastases. Interestingly, activity of anti-EGFR agents on the pathogenesis and
      progression of bone metastases has been described in previous reports, and a
      number of different mechanisms seem to be involved in this phenomenon. Anti-EGFR
      agents have a direct activity on tumour cells in which they produce growth
      inhibition, apoptosis, and reduced invasive capacity through the inhibition of
      molecules associated with tissue invasion such as urokinase-type plasminogen
      activator (uPA) and matrix metalloproteinase (MMP)-9. In addition, these
      compounds have an anti-angiogenic activity, either direct by affecting the
      proliferation and survival of endothelial cells, or indirect by blocking the
      production of vascular endothelial growth factor (VEGF) in bone marrow stromal
      cells and in tumour cells. Finally, EGFR-TKIs can inhibit recruitment of
      osteoclasts in bone lesions, by affecting the ability of bone marrow stromal
      cells to induce osteoclast differentiation and activation. Taken together, these
      findings strongly support prospective clinical trials of anti-EGFR agents in
      cancer patients with bone metastases in order to define their role in the
      management of bone disease.

PMID- 16601276
TI  - Emerging anti-cancer molecular mechanisms of aminobisphosphonates.
AB  - Bone metastases are common in patients with many types of cancer, especially
      breast and prostate cancer--in which the incidence is approximately 70% among
      patients with advanced metastatic disease. Aminobisphosphonates (NBPs) have
      entered clinical practice in the treatment of bone metastases from several
      neoplasms, including breast and prostate adenocarcinoma, as a result of their
      anti-resorption properties. However, evidence has accumulated on the direct anti
      tumour effects of NBPs. This review describes the metabolic pathways that are
      putative molecular targets of NBPs and that are involved in the prenylation
      processes of several intracellular small GTP-binding proteins (ras family related
      proteins). The latter regulate the intracellular survival and proliferative
      pathways of tumour cells and could be the intracellular molecular targets of the
      NBPs responsible for the direct anti-cancer effects, even if definitive
      conclusions cannot be drawn at present. Different mechanisms have been reported
      to account for the anti-neoplastic action of NBPs, including: the induction of
      apoptosis; cell cycle perturbations; and anti-invasive, anti-migration and anti
      angiogenic effects. Moreover, this review describes the most important clinical
      studies that demonstrate the activity of NBPs in preventing skeletal-related
      events induced by bone metastases. The main pharmacokinetic pitfalls of NBPs are
      described, and methods of overcoming these pitfalls through the use of liposome
      vehicles are proposed. Finally, the principal pre-clinical studies on the
      interaction between NBPs and other biological agents are also described; these
      studies may enable reductions in the in vivo NBP concentrations required to
      achieve anti-tumour activity. To date, however, the real molecular targets of
      NBPs are not completely known and new technological platforms are required in
      order to detect them and to develop new anti-cancer strategies based on the use
      of NBPs.

PMID- 16601277
TI  - TRPM8 in prostate cancer cells: a potential diagnostic and prognostic marker with
      a secretory function?
AB  - During the past 5 years it has emerged that the transient receptor potential
      (TRP) family of Ca(2+)-and Na(+)-permeable channels plays a diverse and important
      role in cell biology and in pathology. One member of this family, TRPM8, is
      highly expressed in prostate cancer cells but the physiological and pathological
      functions of TRPM8 in these cells are not known. Here we address these questions,
      and the issue of whether or not TRPM8 is an effective diagnostic and prognostic
      marker in prostate cancer. TRPM8 is known to be activated by cool stimuli (17-25
      degrees C) and cooling compounds such as menthol. The activation mechanism(s)
      involves voltage sensing of membrane potential, phosphatidylinositol 4,5
      bisphosphate and Ca(2+). In addition to prostate cancer cells, TRPM8 is expressed
      in sensory neurons where it acts as a sensor of cold. In prostate epithelial
      cells, expression of TRPM8 is regulated by androgen and is elevated in androgen
      sensitive cancerous cells compared with normal cells. While there is some
      evidence that in prostate cancer cells Ca(2+) and Na(+) inflow through TRPM8 is
      necessary for survival and function, including secretion at the apical membrane,
      the function of TRPM8 in these cells is not really known. It may well differ from
      the role of TRPM8 as a cool sensor in sensory nerve cells. Androgen unresponsive
      prostate cancer is difficult to treat effectively and there are limited
      diagnostic and prognostic markers available. TRPM8 is a potential tissue marker
      in differential diagnosis and a potential prognostic marker for androgen
      unresponsive and metastatic prostate cancer. As a consequence of its ability to
      convey Ca(2+) and Na(+) and its expression in only a limited number of cell
      types, TRPM8 is considered to be a promising target for pharmaceutical,
      immunological and genetic interventions for the treatment of prostate cancer.

PMID- 16601278
TI  - Activation of multiple cancer-associated genes at the ERBB2 amplicon in breast
      cancer.
AB  - During the past decade the role of the ERBB2 (neu/HER2) oncogene as an important
      predictor of patient outcome and response to various therapies in breast cancer
      has been clearly established. This association of ERBB2 aberrations with more
      aggressive disease and poor clinical outcome, together with the high prevalence
      of such alterations in breast cancer, has also made ERBB2 an attractive target
      for therapy. A specific antibody-based therapy, Herceptin, directed against the
      extracellular domain of the ERBB2 receptor tyrosine kinase, was recently
      developed and several clinical trials have shown the therapeutic efficacy of this
      drug against ERBB2-positive breast cancer. However, a relatively large fraction
      of patients does not benefit from Herceptin treatment, indicating that other
      factors beyond ERBB2 itself must influence therapy response in ERBB2-positive
      tumors. It is well known that amplification of the 17q12-q21 region is the most
      common mechanism for ERBB2 activation in breast cancer and that it leads to
      simultaneous activation of several other genes. These co-amplified and co
      activated genes may have an impact on disease progression and the clinical
      behavior of ERBB2-positive tumors and thus represent important targets of
      research. In this paper we discuss the current knowledge on the structure of the
      ERBB2 amplicon, the genes involved, and their possible contribution to breast
      cancer pathogenesis.

PMID- 16601279
TI  - Clinical trials with retinoids for breast cancer chemoprevention.
AB  - Retinoids have been studied as chemopreventive agents in clinical trials due to
      their established role in regulating cell growth, differentiation and apoptosis
      in preclinical models. Experimental evidence suggests that retinoids affect gene
      expression both directly, by activating and/or repressing specific genes, and
      indirectly, by interfering with different signal transduction pathways. Induction
      of apoptosis is a unique feature of fenretinide, the most widely studied retinoid
      in clinical trials on breast cancer chemoprevention due to its selective
      accumulation in breast tissue and to its favourable toxicological profile. In a
      phase III breast cancer prevention trial, fenretinide showed a durable trend to a
      reduction of second breast malignancies in premenopausal women. This pattern was
      associated with a favourable modulation of circulating IGF-I and its main binding
      protein (IGF-binding protein-3, IGFBP-3), which have been associated with breast
      cancer risk in premenopausal women in different prospective studies. In a
      subsequent biomarker study on premenopausal women who had participated in the
      phase III trial, high IGF-I and low IGFBP-3 baseline levels were found to predict
      second breast cancer risk, although the magnitude of their changes during
      treatment did not fulfil the requirements for suitable surrogate end-point
      biomarkers. In postmenopausal women, fenretinide did not reduce second breast
      cancer incidence, nor did it induce significant modulation of the IGF system.
      Similarly, fenretinide was not found to affect risk biomarkers significantly in
      early postmenopausal women on hormone replacement therapy, who are at increased
      risk of developing breast cancer. Biomarker studies of fenretinide alone or in
      combination with different nuclear receptor ligands are being conducted. In
      particular, clinical trials of fenretinide and tamoxifen have proved to be
      feasible, and this combination appears to be safe and well tolerated in high-risk
      women, especially when low-dose tamoxifen is employed. Novel retinoid X receptor
      selective retinoids, or rexinoids, have been shown to suppress the development of
      breast cancer in several animal models with minimal toxicity, and are being
      intensively studied either alone or in combination with selective oestrogen
      receptor modulators, both in vitro and in vivo. The rexinoid, bexarotene, has
      recently been approved for the treatment of patients with cutaneous T-cell
      lymphoma, and a biomarker trial with bexarotene in women with high breast cancer
      risk is currently underway.

PMID- 16601280
TI  - Somatostatin receptor subtype 5 (SSTR5) mRNA expression is related to
      histopathological features of cell proliferation in insulinomas.
AB  - Insulinomas are rare endocrine neoplasias that constitute the most frequent islet
      cell tumours. Somatostatin (SST) analogs are tentatively used to inhibit insulin
      secretion and control tumour growth in patients with local invasion or
      inoperative metastasis, but variable responses have been reported. Data regarding
      somatostatin receptor (SSTR) subtypes expression in insulinomas are conflicting.
      In this study, we evaluated 16 cases of primary insulinomas (including four
      primary plurihormonal tumours) and two hepatic metastases. Histopathological and
      immunohistochemical analysis for some features associated with tumour
      aggressiveness and semi-quantitative RT-PCR for SSTR1-5 and real-time qPCR for
      SSTR5 were performed. SSTR subtypes 1, 3, and 5 were expressed in 100%, SSTR2 in
      89%, and SSTR4 only in 22% of the insulinomas. SSTR5 mRNA was positively
      correlated with histopathological features related to tumour aggressiveness
      (large tumour diameter, well-differentiated endocrine tumour with uncertain
      behaviour and higher number of cells with nuclear atypia). SSTR5 mRNA expression
      in primary insulinomas was lower than in primary plurihormonal tumours (P <
      0.05). The observed positive correlation between SSTR5 expression and tumour size
      suggests that the use of SST analogues more specific to SSTR5 in the treatment of
      insulinomas deserves attention.

PMID- 16601281
TI  - Characterization of the functional and growth properties of long-term cell
      cultures established from a human somatostatinoma.
AB  - In somatostatinoma, a rare malignant somatostatin (SST)-secreting neoplasia,
      tumour regression is rarely observed, implying the need for novel
      antiproliferative strategies. Here, we characterized a long-term culture (SST
      secreting cancer (SS-C cells)) established from a human somatostatinoma. High
      concentrations of SST and chromogranin A were released by SS-C cells and SST
      release was stimulated by depolarizing stimuli and inhibited by the SST analogue,
      octreotide. SS-C cells expressed mRNA for SST receptor (SSTR) subtypes 1, 2 and
      4, being also able to bind native SST. Moreover, SS-C cells were positively
      stained with an antibody to SSTR2. SS-C cells also expressed interferon-gamma
      (IFN-gamma) receptor mRNA and measurable telomerase activity. Our findings
      indicate that in vitro exposure of SS-C cells to native SST-28, to octreotide, to
      IFN-gamma, or to 3'-azido-3'deoxythymidine (AZT), a telomerase inhibitor, results
      in inhibition of SS-C cell proliferation. Concomitant with growth inhibition,
      apoptosis was detected in SST-, octreotide-, IFN-gamma- or AZT-treated SS-C cell
      cultures. Taken together our results characterized native SST, SST analogues, IFN
      gamma and a telomerase inhibitor as growth-inhibiting and proapoptotic stimuli in
      cultured human somatostatinoma cells. Based on these findings, the potential of
      SST analogues, IFN-gamma and AZT, alone or in combination, should be further
      explored in the medical treatment of somatostatinoma.

PMID- 16601282
TI  - A molecular mimic demonstrates that phosphorylated human prolactin is a potent
      anti-angiogenic hormone.
AB  - S179D prolactin (PRL) is an experimentally useful mimic of naturally
      phosphorylated human prolactin. S179D PRL, but not unmodified PRL, was found to
      be anti-angiogenic in both the chorioallantoic membrane and corneal assays.
      Further investigation using human endothelial in vitro models showed reduced cell
      number, reduced tubule formation in Matrigel, and reduced migration and invasion,
      as a function of treatment with S179D PRL. Analysis of growth factors in human
      endothelial cells in response to S179D PRL showed: a decreased expression or
      release of endogenous PRL, heme-oxygenase-1, basic fibroblast growth factor
      (bFGF), angiogenin, epidermal growth factor and vascular endothelial growth
      factor; and an increased expression of inhibitors of matrix metalloproteases.
      S179D PRL also blocked signaling from bFGF in these cells. We conclude that this
      molecular mimic of a pituitary hormone is a potent anti-angiogenic protein,
      partly as a result of its ability to reduce utilization of several well
      established endothelial autocrine growth loops, partly by its ability to block
      signaling from bFGF and partly because of its ability to decrease endothelial
      migration. These findings suggest that circulating levels of phosphorylated PRL
      may influence the progression of cancer and, furthermore, that S179D PRL may be a
      useful anti-angiogenic therapeutic.

PMID- 16601284
TI  - The insulin-like growth factor receptor 1 is a promising target for novel
      treatment approaches in neuroendocrine gastrointestinal tumours.
AB  - Gastrointestinal neuroendocrine tumours (NET) represent a heterogeneous tumour
      entity. The anti-neoplastic therapy of advanced NET disease is still
      unsatisfactory and innovative therapeutic approaches are needed. As NET
      frequently express insulin-like growth factors (IGFs) and their receptors (IGFR),
      known to promote survival, oncogenic transformation, tumour growth and spreading,
      the inhibition of the IGF/IGF-receptor system may offer possibilities for novel
      targeted treatment strategies of NET. Here, we studied the anti-neoplastic
      effects of an inhibition of the IGF-I receptor (IGF-1R) signalling in NET cells
      by the novel IGF-1R tyrosine kinase (TK) inhibitor NVP-AEW541, whose anti
      neoplastic potency has not yet been tested in NET disease. Using two human NET
      cell lines with different growth characteristics, we demonstrated that NVP-AEW541
      dose-dependently inhibited the proliferation of NET cells by inducing apoptosis
      and cell cycle arrest. Anti-neoplastic effects of NVP-AEW541 were also detected
      in primary cultures of human neuroendocrine gastrointestinal tumours. Apoptosis
      was characterized by activation of the apoptotic key enzyme, caspase-3, as well
      as by detection of changes in the expression of the pro- and anti-apoptotic
      proteins, BAX and Bcl-2, after NVP-AEW541 treatment. Cell cycle was arrested at
      the G1/S checkpoint. The anti-neoplastic effects of NVP-AEW541 involved the
      inactivation of ERK1/2. Induction of immediate cytotoxicity did not account for
      the anti-neoplastic effects of NVP-AEW541, as shown by measurement of lactate
      dehydrogenase release. Moreover, additive anti-neoplastic effects were observed
      when NVP-AEW541 was combined with cytostatics such as doxorubicin or the 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin. This is the
      first report on the induction of apoptosis and cell cycle arrest by the IGF-1R-TK
      inhibitor, NVP-AEW541, in NET cells. The inhibition of the IGF/IGFR system
      appears to be a promising novel approach for future treatment strategies of NET
      disease.

PMID- 16601283
TI  - Gender difference in the activity but not expression of estrogen receptors alpha
      and beta in human lung adenocarcinoma cells.
AB  - The higher frequency of lung adenocarcinoma in women smokers than in men smokers
      suggests a role for gender-dependent factors in the etiology of lung cancer. We
      evaluated estrogen receptor (ER) alpha and beta expression and activity in human
      lung adenocarcinoma cell lines and normal lung fibroblasts. Full-length ERalpha
      and ERbeta proteins were expressed in all cell lines with higher ERbeta than
      ERalpha. Although estradiol (E(2)) binding was similar, E(2) stimulated
      proliferation only in cells from females, and this response was inhibited by anti
      estrogens 4-hydroxytamoxifen (4-OHT) and ICI 182,780. In contrast, E(2) did not
      stimulate replication of lung adenocarcinoma cells from males and 4-OHT or ICI
      did not block cell proliferation. Similarly, transcription of an estrogen
      response element-driven reporter gene was stimulated by E(2) in lung
      adenocarcinoma cells from females, but not males. Progesterone receptor (PR)
      expression was increased by E(2) in two out of five adenocarcinoma cell lines
      from females, but none from males. E(2) decreased E-cadherin protein expression
      in some of the cell lines from females, as it did in MCF-7 breast cancer cells,
      but not in the cell lines from males. Thus, ERalpha and ERbeta expression does
      not correlate with the effect of ER ligands on cellular activities in lung
      adenocarcinoma cells. On the other hand, coactivator DRIP205 expression was
      higher in lung adenocarcinoma cells from females versus males and higher in
      adenocarcinoma cells than in normal human bronchial epithelial cells. DRIP205 and
      other ER coregulators may contribute to differences in estrogen responsiveness
      between lung adenocarcinoma cells in females and males.

PMID- 16601285
TI  - Androgen deprivation induces human prostate epithelial neuroendocrine
      differentiation of androgen-sensitive LNCaP cells.
AB  - Neuroendocrine (NE) cells are the minor cell populations in normal prostate
      epithelial compartments. During prostate carcinogenesis, the number of NE cells
      in malignant lesions increases, correlating with its tumorigenicity and hormone
      refractory growth. It is thus proposed that cancerous NE cells promote prostate
      cancer (PCa) cell progression and its androgen-independent proliferation,
      although the origin of the cancerous NE cells is not clear. To investigate the
      role of cancerous NE cells in prostate carcinogenesis, we characterized three NE
      subclone cell lines-NE-1.3, NE-1.8 and NE-1.9, which were transdifferentiated
      from androgen-sensitive human PCa LNCaP cells by culturing in an androgen
      depleted environment, resembling clinical androgen-ablation therapy. These
      subclone cells acquire many features of NE cells seen in clinical prostate
      carcinomas, for example exhibiting a neuronal morphology and expressing multiple
      NE markers, including neuron-specific enolase, chromogranin B, neurotensin,
      parathyroid hormone-related peptide, and to a lesser degree for chromogranin A,
      while lacking androgen receptor (AR) or prostate specific antigen (PSA)
      expression. These cells represent terminally differentiated stable cells because
      after 3 months of re-culturing in a medium containing androgenic activity, they
      still retained the NE phenotype and expressed NE markers. Despite these NE cells
      having a slow growth rate, they readily developed xenograft tumors. Furthermore,
      media conditioned by these NE cells exhibited a stimulatory effect on
      proliferation and PSA secretion by LNCaP cells in androgen-deprived conditions.
      Additionally, we found that receptor protein tyrosine phosphatase alpha plays a
      role in upregulating multiple NE markers and acquiring the NE phenotype. These NE
      cells thus represent cancerous NE cells and could serve as a useful cell model
      system for investigating the role of cancerous NE cells in hormone-refractory
      proliferation of PCa cells.

PMID- 16601286
TI  - Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta
      hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor
      in prostate carcinoma.
AB  - Type 2 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) is a multi-functional
      enzyme that possesses 3alpha-, 17beta- and 20alpha-HSD, as well as prostaglandin
      (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG
      metabolism. Type 2 3alpha-HSD was cloned from human prostate, is a member of the
      aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target
      tissues such as the prostate, AKR1C3 catalyzes the conversion of Delta(4)
      androstene-3,17-dione to testosterone, 5alpha-dihydrotestosterone to 5alpha
      androstane-3alpha,17beta-diol (3alpha-diol), and 3alpha-diol to androsterone.
      Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of
      the androgen receptor in these tissues. Tissue distribution studies indicate that
      AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3
      protein expression and its distribution in the prostate, we raised a monoclonal
      antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish
      AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis
      showed that this monoclonal antibody binds to one species of protein in primary
      cultures of prostate epithelial cells and in LNCaP prostate cancer cells.
      Immunohistochemistry with this antibody on human prostate detected strong nuclear
      immunoreactivity in normal stromal and smooth muscle cells, perineurial cells,
      urothelial (transitional) cells, and endothelial cells. Normal prostate
      epithelial cells were only faintly immunoreactive or negative. Positive
      immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11
      cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in
      non-neoplastic changes in the prostate including chronic inflammation, atrophy
      and urothelial (transitional) cell metaplasia. We conclude that elevated
      expression of AKR1C3 is highly associated with prostate carcinoma. Although the
      biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain,
      AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on
      prostatic epithelial cells.

PMID- 16601287
TI  - Epidermal growth factor-induced neuroendocrine differentiation and apoptotic
      resistance of androgen-independent human prostate cancer cells.
AB  - Neuroendocrine differentiation (NED) has been implicated in prostate cancer
      progression and hormone-therapy failure. Neuroendocrine cells are non
      proliferating and escape apoptotic cell death, although their origin and the
      causes of their apoptotic resistance have as yet been poorly elucidated. This
      study demonstrates a new mechanism involved in controlling NED. We report that
      epidermal growth factor (5-50 ng/ml) promotes neuroendocrine-like differentiation
      of androgen-independent DU145 prostate cancer cells. This differentiation is
      associated with an increase in the expression of Neuron Specific Enolase (NSE)
      and a reduction in cell proliferation and is blocked by inhibiting tyrosine
      kinase activity with genistein and with compound 56 (C56). An increase in the
      cAMP level, using dibutryl cAMP (db-cAMP) (1 mM) and isobutylmethylxanthine (100
      microM), does not promote NED by itself, but does increase the effect of EGF on
      NED. In addition, EGF-induced NED protects cells from apoptosis induced with
      thapsigargin (1 microM) by reducing the thapsigargin-induced cytosolic calcium
      overload. In order to describe how EGF-induced NED protects cells against
      thapigargin-induced calcium overload we investigated the spatiotemporal calcium
      signalling linked to apoptosis. By using thapsigargin in various conditions on
      DU145 cells and using micro-fluorimetric calcium measurements, we show that
      depletion of intracellular calcium store induces apoptosis and that the amplitude
      and duration of the capacitive calcium entry are two apoptosis-modulating
      parameters. We show that protection against thapsigargin-induced apoptosis
      conferred by NED is achieved by reducing the amount and the speed of calcium that
      can be released from calcium pools, as well as modulating the amplitude of the
      subsequent calcium entry.

PMID- 16601288
TI  - Suppression of EGF-R signaling reduces the incidence of prostate cancer
      metastasis in nude mice.
AB  - The activation of epidermal growth factor receptor (EGF-R) plays a key role in
      the promotion of proliferation and invasion in prostatic carcinoma (PCa).
      Gefitinib (Iressa; ZD1839), an orally active EGF-R tyrosine kinase inhibitor, has
      shown an important anti-proliferative activity in tumors expressing EGF-R both in
      vitro and in vivo. Our aim was to elucidate the role of gefitinib in the
      modulation of the metastatic spread of PCa cells. The therapeutic role of
      gefitinib was investigated by evaluating the proliferative and invasive ability
      of the PCa cell line PC3 and of its high metastatic sub-line, PCb2, by in vitro
      assays and intracardiac injection in nude mice. The inhibitory effect of
      gefitinib was tested in vivo by injecting PCa cells subcutaneously or in the left
      ventricle of nude mice and by administering daily 150 mg/kg of gefitinib. While
      xenograft growth was equally reduced in all PCa lines (about 50%), the bone
      metastasis formation was inhibited especially for the high metastatic PCb2 sub
      line (81%) in comparison to PC3 cells (47%). The comparative in vitro analysis
      among PCa cell lines showed that PCb2 cells were more sensitive to the inhibitory
      effect of gefitinib in their invasive ability compared to parental PC3 cells but
      not in their proliferation rate. Moreover, PCb2 cells demonstrated an increased
      invasive ability in vitro in response to bone stromal cell conditioned medium
      (BCM). The simultaneous presence of 0.1 ng/ml gefitinib was sufficient to reduce
      the number of invaded cells in the presence of both EGF and BCM. The molecular
      characterization of the highly aggressive PCa sub-lines demonstrated that this
      phenomenon was associated with an increment in uPA/uPAR axis but not in EGF-R
      expression. In conclusion, our data suggest that the use of gefitinib as a
      therapeutic agent may be indicated in the control of PCa spreading to bone.

PMID- 16601289
TI  - Mechanism of gonadotropin-releasing hormone (GnRH)-I and -II-induced cell growth
      inhibition in ovarian cancer cells: role of the GnRH-I receptor and protein
      kinase C pathway.
AB  - In our previous studies, we demonstrated that ERK1/2 (extracellular signal
      regulated protein kinase) and p38 MAPK (mitogen-activated protein kinase) are
      required for gonadotropin-releasing hormone (GnRH)-II-induced anti-proliferation
      of ovarian cancer cells. In the present study, we examined the role of the GnRH-I
      receptor, as well as the activation of protein kinase C (PKC), in the anti
      proliferative effect induced by GnRH-I or II in ovarian cancer cells. Our results
      demonstrated that Antide, a GnRH-I antagonist, reversed the activation of ERK1/2
      induced by GnRH-I or II and abolished the anti-proliferative effect of GnRH-I and
      II in ovarian cancer cells. Transfection of short-interfering RNA to abrogate the
      gene expression of the GnRH-I receptor reversed GnRH-I and II-induced anti
      proliferation. These results indicate that GnRH-I or II induce anti-proliferation
      through the GnRH-I receptor in ovarian cancer cells. In addition, the activation
      of ERK1/2 by GnRH-I or II was mimicked by phorbol-12-myristate 13-acetate, a PKC
      activator. Pretreatment with GF109203X, an inhibitor of PKC, blocked GnRH-induced
      ERK1/2 activation and anti-proliferation. These results suggest that the
      activation of PKC is responsible for GnRH-induced ERK1/2 activation and anti
      proliferation in ovarian cancer cells. Taken together, these results indicate
      that binding of GnRH-I and II to the GnRH-I receptor activates ERK1/2 through a
      PKC-dependent pathway and is essential for GnRH-induced anti-proliferation of
      ovarian cancer cells.

PMID- 16601290
TI  - Role of exon-16-deleted HER2 in breast carcinomas.
AB  - A splice variant of the human gene HER2, lacking exon-16 (DeltaHER2) which
      encodes a small extracellular region, has been described. This altered receptor
      forms disulfide bond-stabilized homodimers. We report here that the DeltaHER2
      splice variant represents about 9% of the HER2 mRNA obtained from most of the 46
      breast carcinoma samples with HER2 expression levels ranging from 3+ to 0 by
      HercepTest. Analysis of human cells transfected with DeltaHER2 or wild-type (WT)
      cDNA revealed no growth of WT cells in nude mice, whereas clones expressing 10
      fold less DeltaHER2 were tumorigenic. Unlike WT transfectants, DeltaHER2
      expressing cells showed low sensitivity to two new therapeutic drugs targeting
      receptors of the HER family (ZD1839 and Trastuzumab), whereas an inhibitor of the
      HER2 tyrosine kinase domain (Emodin) blocked activation of both DeltaHER2 and WT
      transfectants. Taken together, our findings indicate that the DeltaHER2
      transcript encodes the transforming form of the oncoprotein. It is plausible that
      malignant transformation arises when a critical threshold of DeltaHER2 is reached
      in HER2-overexpressing tumors. Specific inhibitors of HER2 catalytic activity
      represent a promising approach to therapy of HER2-overexpressing tumors.

PMID- 16601291
TI  - Peroxisome proliferator-activated receptor gamma in human breast carcinoma: a
      modulator of estrogenic actions.
AB  - It has been reported that agonists of peroxisome proliferator-activated receptor
      gamma (PPARgamma) inhibit proliferation of breast carcinoma cells, but the
      biological significance of PPARgamma remains undetermined in human breast
      carcinomas. Therefore, we immunolocalized PPARgamma in 238 human breast carcinoma
      tissues. PPARgamma immunoreactivity was detected in 42% of carcinomas, and was
      significantly associated with the status of estrogen receptor (ER) alpha, ERbeta,
      progesterone receptor, retinoic X receptors, p21 or p27, and negatively
      correlated with histological grade or cyclooxygenase-2 status. PPARgamma
      immunoreactivity was significantly associated with an improved clinical outcome
      of breast carcinoma patients by univariate analysis, and multivariate analysis
      demonstrated that PPARgamma immunoreactivity was an independent prognostic factor
      for overall survival in ERalpha-positive patients. We then examined possible
      mechanisms of modulation by PPARgamma on estrogenic actions in MCF-7 breast
      carcinoma cells. A PPARgamma activator, 15-deoxy-Delta(12,14)- prostaglandin J(2)
      (15d-PGJ(2)), significantly inhibited estrogen-responsive element-dependent
      transactivation by estradiol in MCF-7 cells, which was blocked by addition of a
      PPARgamma antagonist GW9662. Subsequent study, employing a custom-made microarray
      focused on estrogen-responsive genes, revealed that mRNA expression was
      significantly regulated by estradiol in 49 genes, but this significance vanished
      on addition of 15d-PGJ(2) in 16 out of 49 (33%) genes. These findings were
      confirmed by real-time PCR in 11 genes. 15d-PGJ(2) significantly inhibited
      estrogen-mediated proliferation of MCF-7 cells, and caused accumulation of p21
      and p27 protein. These results suggest that PPARgamma is mainly expressed in well
      differentiated and ER-positive breast carcinomas, and modulates estrogenic
      actions.

PMID- 16601292
TI  - Endocrine response after prior treatment with fulvestrant in postmenopausal women
      with advanced breast cancer: experience from a single centre.
AB  - The pure anti-oestrogen fulvestrant has now been licensed for use in advanced
      breast cancer which has progressed on an anti-oestrogen. Optimal sequencing of
      various endocrine agents becomes very important in the therapeutic strategy. We
      report our experience of further endocrine response with another endocrine agent
      after prior fulvestrant treatment. Among all patients with advanced breast cancer
      who had been entered into five phase II/III trials using fulvestrant as first- to
      ninth-line endocrine therapy in our Unit since 1993, 54 patients who fulfilled
      the following criteria were studied for their subsequent endocrine response: (i)
      oestrogen receptor positive or unknown; (ii) having been on a subsequent
      endocrine therapy for > or =6 months unless the disease progressed before; and
      (iii) with disease assessable for response according to International Union
      Against Cancer criteria. Eleven patients had received an aromatase inhibitor
      prior to fulvestrant, which resulted in five CBs (clinical benefit = objective
      remission/stable disease (SD)) for > or =6 months). Twenty-eight patients
      achieved CB on fulvestrant. They went on subsequent endocrine therapy with two
      partial responses, 11 SDs and 15 PDs (progressive disease) at 6 months. The
      median survival from starting fulvestrant and subsequent endocrine therapy was
      respectively 46.6 and 18.2 months. Among the remaining 26 patients who progressed
      at 6 months on fulvestrant, there were three SDs and 23 PDs at 6 months on
      subsequent endocrine therapy. The median survival from starting fulvestrant and
      subsequent endocrine therapy was respectively 12.5 and 9.3 months. Of all these
      54 patients, 30% (n = 16) therefore achieved CB using another (second- to tenth
      line) endocrine agent (anastrozole = 26; tamoxifen = 12; megestrol acetate = 11;
      others = 5). It would thus appear that further endocrine response can be induced
      in a reasonable proportion of patients after failing fulvestrant.

PMID- 16601293
TI  - The oncogene BRAF V600E is associated with a high risk of recurrence and less
      differentiated papillary thyroid carcinoma due to the impairment of Na+/I-
      targeting to the membrane.
AB  - The oncogene BRAF(V600E) is the most frequent genetic event in papillary thyroid
      carcinoma (PTC) but its prognostic impact still remains to be elucidated. We
      evaluated a representative series of 67 individuals with PTC who underwent total
      thyroidectomy. BRAF-positive tumours correlated with early recurrences (32% vs
      7.6%; P=0.02) during a median postoperative follow-up period of 3 years.
      Interestingly, within the recurrences, a significant majority had negative
      radioiodine ((131)I) total body scans, predicting a poorer outcome as treatment
      with (131)I is not effective. This last observation led us to investigate the
      role of BRAF(V600E) and the MEK-ERK pathway in thyroid dedifferentiation,
      particularly in Na(+)/I(-) symporter (NIS) impairment, as this thyroid-specific
      plasma membrane glycoprotein mediates active transport of I(-) into the thyroid
      follicular cells. A subset of 60 PTC samples was evaluated for NIS
      immunoreactivity and, accordingly, we confirmed a significant low NIS expression
      and impaired targeting to membranes in BRAF-positive samples (3.5% vs 30%;
      P=0.005). Furthermore, experiments with differentiated PCCl3 thyroid cells
      demonstrated that transient expression of BRAF(V600E) sharply impaired both NIS
      expression and targeting to membrane and, surprisingly, this impairment was not
      totally dependent on the MEK-ERK pathway. We have concluded that BRAF(V600E) is a
      new prognostic factor in PTC that correlates with a high risk of recurrences and
      less differentiated tumours due to the loss of NIS-mediated (131)I uptake.

PMID- 16601294
TI  - Sense primer used to amplify rat angiotensinogen mRNA is against an intron.

PMID- 16601296
TI  - Regulation of the epithelial Na+ channel (ENaC) by phosphatidylinositides.
AB  - The epithelial Na(+) channel (ENaC) is an end-effector of diverse cellular
      signaling cascades, including those with phosphatidylinositide second messengers.
      Recent evidence also suggests that in some instances, phospatidylinositides can
      directly interact with ENaC to increase channel activity by increasing channel
      open probability and/or membrane localization. We review here findings relevant
      to regulation of ENaC by phosphatidylinositol 4,5-bisphosphate (PIP(2)) and
      phosphatidylinositol 3,4,5-triphosphate (PIP(3)). Similar to its actions on other
      ion channels, PIP(2) is permissive for ENaC openings having a direct effect on
      gating. The PIP(2) binding site in ENaC involved in this regulation is most
      likely localized to the NH(2) terminus of beta-ENaC. PIP(3) also affects ENaC
      gating but, rather than being permissive, augments open probability. The PIP(3)
      binding site in ENaC involved in this regulation is localized to the proximal
      region of the COOH terminus of gamma-ENaC just following the second transmembrane
      domain. In complementary pathways, PIP(3) also impacts ENaC membrane levels
      through both direct actions on the channel and via a signaling cascade involving
      phosphoinositide 3-OH kinase (PI3-K) and the aldosterone-induced gene product
      serum and glucocorticoid-inducible kinase. The putative PIP(3) binding site in
      ENaC involved in direct regulation of channel membrane levels has not yet been
      identified.

PMID- 16601298
TI  - PTH(1-84)/PTH(7-84): a balance of power.
AB  - This review considers many new basic and clinical aspects of parathyroid hormone
      (PTH). We focus especially on the identification of PTH fragments and how they
      may relate to renal failure, diagnosis, and treatment of secondary
      hyperparathyroidism and renal osteodystrophy. The biosynthesis and metabolism of
      PTH, measurement of circulating forms of PTH, the effects of PTH on receptor
      activation and turnover, the relationship between PTH levels and bone turnover in
      renal failure in humans, and the involvement of PTH in experimental models of
      renal failure are discussed. Despite these developments in understanding the
      etiology of renal failure and the availability of new assays for bioactive PTH,
      no adequate surrogate for bone biopsy and quantitative bone histomorphometry has
      been developed.

PMID- 16601299
TI  - Membrane transport proteins: not just for transport anymore.

PMID- 16601297
TI  - Functional MRI of the kidney: tools for translational studies of pathophysiology
      of renal disease.
AB  - Magnetic resonance imaging (MRI) provides exquisite anatomic detail of various
      organs and is capable of providing additional functional information. This
      combination allows for comprehensive diagnostic evaluation of pathologies such as
      ischemic renal disease. Noninvasive MRI techniques could facilitate translation
      of many studies performed in controlled animal models using technologies that are
      invasive to humans. Such a translation is being recognized as essential because
      many proposed interventions and drugs that prove efficacious in animal models
      fail to do so in humans. In this article, we review the state-of-the-art
      functional MRI technique as applied to the kidneys.

PMID- 16601300
TI  - Binding characteristics of a panel of monoclonal antibodies against the ligand
      binding domain of the human LDLr.
AB  - To obtain a panel of monoclonal antibodies (MAbs) to study the folding and
      conformation of the low density lipoprotein receptor (LDLr), we have generated
      hybridomas from LDLr-deficient mice that had been immunized with the
      extracellular domain of the human LDLr. The 12 MAbs were specific for the ligand
      binding domain of the LDLr, with individual MAbs recognizing epitopes in ligand
      binding repeats 1, 2, 3, 5, and 7. A subset of the MAbs failed to react with the
      LDLr when disulfide bonds were reduced, and one MAb, specific for an epitope that
      spans ligand binding repeats 1 and 2, recognized two conformational forms of the
      LDLr with different affinities. Antibodies specific for ligand binding repeats 3,
      5, and 7 completely blocked the binding of LDL particles to the LDLr on cultured
      human fibroblasts, whereas MAbs with epitopes in ligand binding repeats 1 and 2
      partially blocked the binding of LDL to the LDLr. These anti-LDLr MAbs will serve
      as useful probes for further analysis of LDLr conformation and LDLr-mediated
      lipoprotein binding.

PMID- 16601301
TI  - Myogenic gene expression at rest and after a bout of resistance exercise in young
      (18-30 yr) and old (80-89 yr) women.
AB  - The purpose of this study was to investigate mRNA expression of several key
      skeletal muscle myogenic controllers; myogenic differentiation factor (MyoD),
      muscle regulatory factor 4 (MRF4), myogenic factor 5 (Myf5), myogenin, myostatin,
      and myocyte enhancer factor 2 (MEF2) at rest and 4 h after a single bout of
      resistance exercise (RE) in young and old women. Eight young women (YW; 23 +/- 2
      yr, 67 +/- 5 kg) and six old women (OW; 85 +/- 1 yr, 67 +/- 4 kg) performed 3
      sets of 10 repetitions of bilateral knee extensions at 70% of one repetition
      maximum. Muscle biopsies were taken from the vastus lateralis before and 4 h
      after RE. Using real-time RT PCR, mRNA from the muscle samples was amplified and
      normalized to GAPDH. At rest, OW expressed higher (P < 0.05) levels of MyoD,
      MRF4, Myf5, myogenin, and myostatin compared with YW. In response to RE, there
      was a main time effect (P < 0.05) for the YW and OW combined in the upregulation
      of MyoD (2.0-fold) and MRF4 (1.4-fold) and in the downregulation of myostatin
      (2.2-fold). There was a trend (P = 0.08) for time x age interaction in MRF4.
      These data show that old women express higher myogenic mRNA levels at rest. The
      higher resting myogenic mRNA levels in old women may reflect an attempt to
      preserve muscle mass and function. When challenged with RE, old women appear to
      respond in a similar manner as young women.

PMID- 16601302
TI  - Splenectomy impairs diffusive oxygen transport in the lung of dogs.
AB  - The spleen acts as an erythrocyte reservoir in highly aerobic species such as the
      dog and horse. Sympathetic-mediated splenic contraction during exercise
      reversibly enhances convective O2 transport by increasing hematocrit, blood
      volume, and O2-carrying capacity. Based on theoretical interactions between
      erythrocytes and capillary membrane (Hsia CCW, Johnson RL Jr, and Shah D. J Appl
      Physiol 86: 1460-1467, 1999) and experimental findings in horses of a
      postsplenectomy reduction in peripheral O2-diffusing capacity (Wagner PD,
      Erickson BK, Kubo K, Hiraga A, Kai M, Yamaya Y, Richardson R, and Seaman J.
      Equine Vet J 18, Suppl: 82-89, 1995), we hypothesized that splenic contraction
      also augments diffusive O2 transport in the lung. Therefore, we have measured
      lung diffusing capacity (DL(CO)) and its components during exercise by a
      rebreathing technique in six adult foxhounds before and after splenectomy.
      Splenectomy eliminated exercise-induced polycythemia, associated with a 30%
      reduction in maximal O2 uptake. At any given pulmonary blood flow, DL(CO) was
      significantly lower after splenectomy owing to a lower membrane diffusing
      capacity, whereas pulmonary capillary blood volume changed variably;
      microvascular recruitment, indicated by the slope of the increase in DL(CO) with
      respect to pulmonary blood flow, was also reduced. We conclude that splenic
      contraction enhances both convective and diffusive O2 transport and provides
      another compensatory mechanism for maintaining alveolar O2 transport in the
      presence of restrictive lung disease or ambient hypoxia.

PMID- 16601303
TI  - Active hyperemia and vascular conductance differ between men and women for an
      isometric fatiguing contraction.
AB  - To understand the role of muscle perfusion in the sex differences of muscle
      fatigue, we compared the time to task failure, postcontraction (active)
      hyperemia, and vascular conductance for an isometric fatiguing contraction
      performed by young men and women with the handgrip muscles at 20% of maximal
      voluntary contraction (MVC) force. In study 1, the men (n = 16) were stronger
      than the women (n = 18), and study 2, the men (n = 7) and women (n = 7) were
      matched for strength. Isometric contractions were sustained during two sessions:
      1) until the target force could no longer be achieved or 2) for 4 min. For both
      studies, blood flow and vascular conductance were similar for the men and women
      at rest and after 10 min of occlusion, and at task failure for the fatiguing
      contraction estimated using forearm venous occlusion plethysmography. In study 1,
      the time to task failure was longer for the women (11.4 +/- 2.8 min) than for the
      men (8.4 +/- 2.4 min; P = 0.003). However, at the end of the 4-min contraction,
      active hyperemia and vascular conductance were greater for the men than the women
      (99 vs. 70% peak blood flow; P < 0.001). In study 2, the men and women had
      similar strength and a similar time to failure (8.4 +/- 1.6 vs. 8.6 +/- 2.3 min).
      Active hyperemia was greater for the men than the women (86 vs. 64% peak flow; P
      = 0.038) after the 4-min contraction, as was vascular conductance (80 vs. 57%
      peak conductance; P = 0.02). Thus the briefer time to failure of men than women
      for an isometric fatiguing contraction is a function of the greater strength of
      men but is not dependent on differences in the active hyperemia and vascular
      conductance.

PMID- 16601304
TI  - Effect of flywheel-based resistance exercise on processes contributing to muscle
      atrophy during unloading in adult rats.
AB  - Flywheel-based resistance exercise (RE) attenuates muscle atrophy during hindlimb
      suspension. We have previously shown that protein synthesis is elevated in
      response to RE, but the effect on protein degradation, cell proliferation, or
      apoptosis was not investigated. We hypothesized that, in addition to affecting
      protein synthesis, RE inhibits processes that actively contribute to muscle
      atrophy during hindlimb suspension. Male rats were housed in regular cages
      (control), tail suspended for 2 wk (HS), or HS with RE every other day for 2 wk
      (HSRE). Although RE attenuated soleus muscle atrophy during HS, the observed
      fivefold elevation in apoptosis and the 53% decrease in cell proliferation
      observed with HS were unaffected by RE. Expression of genes encoding components
      of the ubiquitin-proteasome pathway of protein degradation were elevated with HS,
      including ubiquitin, MAFbx, Murf-1, Nedd4, and XIAP, and proteasome subunits C2
      and C9. Total ubiquitinated protein was increased with HS, but proteasome
      activity was not different from control. RE selectively altered the expression of
      different components of this pathway: MAFbx, Murf-1, and ubiquitin mRNA abundance
      were downregulated, whereas C2 and C9 subunits remained elevated. Similarly,
      Nedd4 and XIAP continued to be upregulated, potentially accounting for the
      observed augmentation in total ubiquitinated protein with RE. Thus a different
      constellation of proteins is likely ubiquitinated with RE due to altered
      ubiquitin ligase composition. In summary, the flywheel-based resistance exercise
      paradigm used in this study is associated with the inhibition of some mechanisms
      associated with muscle atrophy, such as the increase in MAFbx and Murf-1, but not
      with others, such as proteasome subunit remodeling, apoptosis, and decreased
      proliferation, potentially accounting for the inability to completely restore
      muscle mass. Identifying specific exercise parameters that affect these latter
      processes may be useful in designing effective exercise strategies in the elderly
      or during spaceflight.

PMID- 16601305
TI  - Direct corticospinal pathways contribute to neuromuscular control of perturbed
      stance.
AB  - The antigravity soleus muscle (Sol) is crucial for compensation of stance
      perturbation. A corticospinal contribution to the compensatory response of the
      Sol is under debate. The present study assessed spinal, corticospinal, and
      cortical excitability at the peaks of short- (SLR), medium- (MLR), and long
      latency responses (LLR) after posterior translation of the feet. Transcranial
      magnetic stimulation (TMS) and peripheral nerve stimulation were individually
      adjusted so that the peaks of either motor evoked potential (MEP) or H reflex
      coincided with peaks of SLR, MLR, and LLR, respectively. The influence of
      specific, presumably direct, corticospinal pathways was investigated by H-reflex
      conditioning. When TMS was triggered so that the MEP arrived in the Sol at the
      same time as the peaks of SLR and MLR, EMG remained unaffected. Enhanced EMG was
      observed when the MEP coincided with the LLR peak (P < 0.001). Similarly,
      conditioning of the H reflex by subthreshold TMS facilitated H reflexes only at
      LLR (P < 0.001). The earliest facilitation after perturbation occurred after 86
      ms. The TMS-induced H-reflex facilitation at LLR suggests that increased cortical
      excitability contributes to the augmentation of the LLR peaks. This provides
      evidence that the LLR in the Sol muscle is at least partly transcortical,
      involving direct corticospinal pathways. Additionally, these results demonstrate
      that approximately 86 ms after perturbation, postural compensatory responses are
      cortically mediated.

PMID- 16601306
TI  - Vital capacity, respiratory muscle strength, and pulmonary gas exchange during
      long-duration exposure to microgravity.
AB  - Extended exposure to microgravity (microG) is known to reduce strength in weight
      bearing muscles and was also reported to reduce respiratory muscle strength.
      Short- duration exposure to microG reduces vital capacity (VC), a surrogate
      measure for respiratory muscle strength, for the first few days, with little
      change in O2 uptake, ventilation, or end-tidal partial pressures. Accordingly we
      measured VC, maximum inspiratory and expiratory pressures, and indexes of
      pulmonary gas exchange in 10 normal subjects (9 men, 1 woman, 39-52 yr) who lived
      on the International Space Station for 130-196 days in a normoxic, normobaric
      atmosphere. Subjects were studied four times in the standing and supine postures
      preflight at sea level at 1 G, approximately monthly in microG, and multiple
      times postflight. VC in microG was essentially unchanged compared with preflight
      standing [5.28 +/- 0.08 liters (mean +/- SE), n = 187; 5.24 +/- 0.09, n = 117,
      respectively; P = 0.03] and considerably greater than that measured supine in 1G
      (4.96 +/- 0.10, n = 114, P < 0.001). There was a trend for VC to decrease after
      the first 2 mo of microG, but there were no changes postflight. Maximum
      respiratory pressures in microG were generally intermediate to those standing and
      supine in 1G, and importantly they showed no decrease with time spent in microG.
      O2 uptake and CO2 production were reduced (approximately 12%) in extended microG,
      but inhomogeneity in the lung was not different compared with short-duration
      exposure to microG. The results show that VC is essentially unchanged and
      respiratory muscle strength is maintained during extended exposure to microG, and
      metabolic rate is reduced.

PMID- 16601307
TI  - Reflexes from the lungs and airways: historical perspective.
AB  - Historical aspects of respiratory reflexes from the lungs and airways are
      reviewed, up until about 10 yr ago. For most of the 19th century, the possible
      reflex inputs into the "respiratory center," the position of which had been
      identified, were very speculative. There was little concept of reflex control of
      the pattern of breathing. Then, in 1868, Breuer published his paper on "The self
      steering of respiration via the Nervus Vagus." For the first time this
      established the role of vagal inflation and deflation reflexes in determining the
      pattern of breathing. Head later extended Breuer's work, and Kratschmer laid a
      similar basis for reflexes from the nose and larynx. Then, 50-60 yr later, the
      development of the thermionic valve and the oscilloscope allowed recording action
      potentials from single nerve fibers in the vagus. In 1933, Adrian showed that
      slowly adapting pulmonary stretch receptors were responsible for the inflation
      reflex. Later, Knowlton and Larrabee described rapidly adapting receptors and
      showed that they mediated deep augmented breaths and the deflation reflex. Still
      later, it was established that rapidly adapting receptors were, at least in part,
      responsible for cough. In 1954, Paintal began his study of C-fiber receptors (J
      receptors), work greatly extended by the Coleridges. Since approximately 10 yr
      ago, when the field of this review stops, there has been an explosion of research
      on lung and airway receptors, many aspects of which are dealt with in other
      papers in this series.

PMID- 16601308
TI  - Steep head-down tilt has persisting effects on the distribution of pulmonary
      blood flow.
AB  - Head-down tilt has been shown to increase lung water content in animals and alter
      the distribution of ventilation in humans; however, its effects on the
      distribution of pulmonary blood flow in humans are unknown. We hypothesized that
      head-down tilt would increase the heterogeneity of pulmonary blood flow in
      humans, an effect analogous to the changes seen in the distribution of
      ventilation, by increasing capillary hydrostatic pressure and fluid efflux in the
      lung. To test this, we evaluated changes in the distribution of pulmonary blood
      flow in seven normal subjects before and after 1 h of 30 degrees head-down tilt
      using the magnetic resonance imaging technique of arterial spin labeling. Data
      were acquired in triplicate before tilt and at 10-min intervals for 1 h after
      tilt. Pulmonary blood flow heterogeneity was quantified by the relative
      dispersion (standard deviation/mean) of signal intensity for all voxels within
      the right lung. Relative dispersion was significantly increased by 29% after tilt
      and remained elevated during the 1 h of measurements after tilt (0.84 +/- 0.06
      pretilt, 1.09 +/- 0.09 calculated for all time points posttilt, P < 0.05). We
      speculate that the mechanism most likely responsible for our findings is that
      increased pulmonary capillary pressures and fluid efflux in the lung resulting
      from head-down tilt alters regional blood flow distribution.

PMID- 16601309
TI  - Maximal oxygen consumption in relation to subordinate traits in lines of house
      mice selectively bred for high voluntary wheel running.
AB  - We studied relations between maximal O2 consumption (VO2 max) during forced
      exercise and subordinate traits associated with blood O2 transport and cellular
      respiration in four lines of mice selectively bred for high voluntary wheel
      running (S lines) and their four nonselected control (C) lines. Previously, we
      reported VO2 max of 59 females at three Po2 (hypoxia = 14% O2, normoxia = 21%,
      hyperoxia = 30%). Here, we test the hypothesis that variation in VO2 max can be
      explained, in part, by hemoglobin concentration and Po2 necessary to obtain 50%
      O2 saturation of Hb (an estimate of Hb affinity for O2) of the blood as well as
      citrate synthase activity and myoglobin concentration of ventricles and
      gastrocnemius muscle. Statistical analyses controlled for body mass, compared S
      and C lines, and also considered effects of the mini-muscle phenotype (present
      only in S lines and resulting from a Mendelian recessive allele), which reduces
      hindlimb muscle mass while increasing muscle mass-specific aerobic capacity.
      Although S lines had higher VO2 max than C, subordinate traits showed no
      statistical differences when the presence of the mini-muscle phenotype was
      controlled. However, subordinate traits did account for some of the individual
      variation in VO2 max. Ventricle size was a positive predictor of VO2 max at all
      three Po2. Blood Hb concentration was a positive predictor of VO2 max in S lines
      but a negative predictor in C lines, indicating that the physiological
      underpinnings of VO2 max have been altered by selective breeding. Mice with the
      mini-muscle phenotype had enlarged ventricles, with higher mass-specific citrate
      synthase activity and myoglobin concentration, which may account for their higher
      VO2 max in hypoxia.

PMID- 16601310
TI  - Objective evaluation of changes in left ventricular and atrial volumes during
      parabolic flight using real-time three-dimensional echocardiography.
AB  - We tested the feasibility of real-time three-dimensional (3D) echocardiographic
      (RT3DE) imaging to measure left heart volumes at different gravity during
      parabolic flight and studied the effects of lower body negative pressure (LBNP)
      as a countermeasure. Weightlessness-related changes in cardiac function have been
      previously studied during spaceflights using both 2D and 3D echocardiography.
      Several technical factors, such as inability to provide real-time analysis and
      the need for laborious endocardial definition, have limited its usefulness. RT3DE
      imaging overcomes these limitations by acquiring real-time pyramidal data sets
      encompassing the entire ventricle. RT3DE data sets were obtained (Philips 7500,
      X3) during breath hold in 16 unmedicated normal subjects in upright standing
      position at different gravity phases during parabolic flight (normogravity, 1 Gz;
      hypergravity, 1.8 Gz; microgravity, 0 Gz), with LBNP applied (-50 mmHg) at 0 Gz
      in selected parabolas. RT3DE imaging during parabolic flight was feasible in 14
      of 16 subjects. Data were analyzed (Tomtec) to quantify left ventricular (LV) and
      atrial (LA) volumes at end diastole and end systole, which significantly
      decreased at 1.8 Gz and increased at 0 Gz. While ejection fraction did not change
      with gravity, stroke volume was reduced by 16% at 1.8 Gz and increased by 20% at
      0 Gz, but it was not significantly different from 1 Gz values with LBNP. RT3DE
      during parabolic flight is feasible and provides the basis for accurate
      quantification of LV and LA volume changes with gravity. As LBNP counteracted the
      increase of LV and LA volumes caused by changes in venous return, it may be
      effectively used for preventing cardiac dilatation during 0 Gz.

PMID- 16601311
TI  - Temperature dependent contribution of Ca2+ transporters to relaxation in cardiac
      myocytes: important role of sarcolemmal Ca2+-ATPase.
AB  - Activities of Ca(2+) -ATPase of sarcoplasmic reticulum (SERCA) and Na(+)/Ca(2+)
      exchanger (NCX) involved in cellular Ca(2+) turnover greatly change in
      hypertrophied and failing hearts. Unfortunately, contribution of these proteins
      as well as of the sarcolemmal Ca(2+)-ATPase (PMCA) to cellular Ca(2+) turnover
      has been investigated almost exclusively at room temperature. PMCA is of
      particular interest since it may affect activity of calcineurin and nNOS.
      Therefore the objective of this study was to reinvestigate contribution of SERCA,
      NCX and PMCA to cell relaxation and the effect of PMCA on cell contraction at 37
      degrees C. Myocytes isolated from the ventricles of guinea pig and rat hearts and
      incubated with Indo-1 were field stimulated at the rate of 60/min. Contribution
      of SERCA, NCX and PMCA was calculated from the rate constants of the decaying
      components of electrically stimulated Ca(2+) transients or of the transients
      initiated by caffeine dissolved in normal Tyrode or in 0Na, 0Ca Tyrode. Increase
      in temperature from 24 to 37 degrees C increased the relative contribution of NCX
      from 6.1% to 7.5% in rat and from 21.3 to 51.9% in guinea pig at the expense of
      SERCA. The contribution of the PMCA to relaxation in both species increased upon
      rise in temperature from 24% to 37 degrees C from negligible values to 3.7%. In
      both species amplitude of Ca(2+) transients was at 24 degrees C nearly twice as
      high as at 37 degrees C. It was nearly doubled by carboxyeosine (CE), a PMCA
      blocker at 37 degrees C but was hardly affected at 24 degrees C. The effects of
      CE were concentration-dependent and conformed with the degree of inhibition of
      activity of PMCA. CONCLUSIONS: PMCA plays an important role in regulation of
      myocardial contraction despite its small contribution to relaxation. In guinea
      pig but not in rat relative contribution of SERCA and NCX to relaxation is highly
      temperature dependent.

PMID- 16601312
TI  - Influence of renal denervation on renal effects of acute nitric oxide and ETA/ETB
      receptor inhibition in conscious normotensive rats.
AB  - The role of renal nerves in the effects of concomitant NO synthase and non
      selective ET(A/)ET(B) receptor inhibition on renal function was investigated in
      conscious normotensive Wistar rats. NO synthase inhibition alone (10 mg/kg b. w.
      i.v. L-NAME) in sham-operated rats with intact renal nerves induced an increase
      in systolic, diastolic and mean arterial pressure, urine flow rate, sodium,
      chloride and calcium excretion (p<0.05). The effect of L-NAME was markedly
      reduced by bosentan (10 mg/kg b.w. i.v.) and the values of urine flow rate,
      sodium, chloride and calcium excretions returned to control level (p<0.05). L
      NAME administration one week after a bilateral renal denervation increased blood
      pressure to a similar extent as in sham-operated rats but decreased urine flow
      rate (p<0.05) and did not change electrolyte excretion. ET(A/)ET(B) receptor
      inhibition with bosentan during NO synthase inhibition in the renal denervated
      rats did not produce changes in urine flow rate or electrolyte excretion. NO
      synthase inhibition as well as concurrent NO synthase and ET(A/)ET(B) receptor
      inhibition did not change clearance of inulin or paraaminohippuric acid in sham
      operated or renal denervated rats. These results indicate that renal sympathetic
      nerves play an important modulatory role in NO and endothelin induced effects on
      renal excretory function.

PMID- 16601313
TI  - Nitric oxide effect on the hemoglobin-oxygen affinity.
AB  - The biological roles of nitric oxide (NO)-hemoglobin (Hb) derivatives are
      obscure. It is proposed that NO can function as an allosteric regulator of
      hemoglobin oxygen-binding properties. We aimed to estimate the effects of NO
      donors and NO-synthase substrate (L-arginine) on hemoglobin-oxygen affinity (HOA)
      in experiments in vitro with the various ratios between NO formed and Hb and
      various oxygen pressures. HOA index (p50), blood pH, plasma and red blood cell
      (RBC) concentrations of nitrite/nitrate and methemoglobin amounts were measured
      after the experiments. In our experiments, blood incubation with NO donors
      (glyceryltrinitrate, molsidomine, sodium nitroprusside, S-nitrosocysteine) or NO
      synthase substrate (L-arginine) did not change HOA even at NO:Hb ratio of 1:1. At
      the same time our results showed that oxygenated blood incubation with S
      nitrosocysteine induced an oxyhemoglobin dissociation curve shift leftwards. This
      indicates a leading role of met-Hb in a modification of Hb oxygen-binding
      properties. However other NO-modified forms of hemoglobin (S-nitroso- and
      nitrosylhemoglobin) also may be involved in the regulation of HOA. The results
      obtained indicate that nitric oxide can be the allosteric effector of hemoglobin,
      increasing or decreasing its oxygen affinity - possibly, through the generation
      of different NO-Hb derivatives.

PMID- 16601314
TI  - Effect of ischemic preconditioning on pancreatic regeneration and pancreatic
      expression of vascular endothelial growth factor and platelet-derived growth
      factor-A in ischemia/reperfusion-induced pancreatitis.
AB  - Ischemic preconditioning has been shown to protect several organs from
      ischemia/reperfusion-induced injury. In the pancreas, protective effect of
      ischemic preconditioning has been shown against pancreatitis evoked by
      ischemia/reperfusion, as well as by caerulein. However, the effect of ischemic
      preconditioning on the course of acute pancreatic is unclear. The aim of our
      study was to evaluate the influence of ischemic preconditioning on pancreatic
      regeneration and pancreatic presence of platelet-derived growth factor-A (PDGF-A)
      and vascular endothelial growth factor (VEGF) in the course of
      ischemia/reperfusion-induced pancreatitis. METHODS: In male Wistar rats, ischemic
      preconditioning of the pancreas was performed by short-term clamping of celiac
      artery (twice for 5 min with 5 min interval). Acute pancreatitis was induced by
      clamping of inferior splenic artery for 30 min followed by reperfusion. Rats were
      sacrificed 1, 5, 12 h or 1, 2, 3, 5, 7, 9 and 21 days after the start of
      reperfusion. Severity of acute pancreatitis and pancreatic regeneration were
      determined by biochemical and morphological examination, expression of growth
      factors was determined by immunohistochemical analysis. RESULTS: In
      ischemia/reperfusion-induced pancreatitis, the pancreatic damage reached the
      maximal range between the first and second day of reperfusion, and was followed
      by subsequent pancreatic regeneration. Ischemic preconditioning alone caused mild
      passing pancreatic damage and an increase in plasma concentration of pro
      inflammatory interleukin-1 and anti-inflammatory interleukin-10. Ischemic
      preconditioning applied before ischemia/reperfusion-induced pancreatitis reduced
      morphological and biochemical signs of the pancreatitis-evoked pancreatic damage
      and accelerated pancreatic regeneration. This effect was associated with
      improvement of pancreatic blood flow. Ischemic preconditioning,
      ischemia/reperfusion-induced pancreatitis and their combination increased the
      presence of VEGF in acinar and islet cells, and immunostaining for PDGF-A in
      blood vessels. This effect was maximally pronounced after combination of ischemic
      preconditioning plus pancreatitis and occurred earlier than after pancreatitis
      alone. CONCLUSIONS: Ischemic preconditioning reduces pancreatic damage and
      accelerates pancreatic healing in the course of ischemia/reperfusion-induced
      pancreatitis. This effect is associated with the increase in plasma concentration
      of anti-inflammatory interleukin-10, improvement of pancreatic blood flow and
      alteration of pancreatic immunohistochemical expression of PDGF-A and VEGF.

PMID- 16601315
TI  - Quantitative characteristics of somatostatin-like cells in the stomach of uraemic
      rats.
AB  - Metabolic disorders induced by impairment of renal parenchyma functions affect
      the activity of the endocrine cells of the APUD system, which are of importance
      in the intrinsic regulatory system in the digestive tract. For this reason, the
      author decided to investigate the behaviour of neuroendocrine cells in
      experimental uraemia, taking somatostatin-producing cells as an example. The aim
      of the present study was to examine the number and distribution of somatostatin
      containing cells in the pylorus of rats with uraemia. Segments of the gastric
      pylorus were collected 1, 2 and 4 weeks after nephrectomy. Paraffin-embedded
      sections were stained with H+E and by silver impregnation. To identify the
      neuroendocrine cells, on immunohistochemical reaction was performed with a
      specific antibody against somatostatin. It was found that the number of ST
      immunoreactive cells in the stomach of the rats significantly decreased one week
      after nephrectomy and then considerably increased two and four weeks after the
      uraemia-inducing surgery as compared with the values in the control animals. The
      results can be regarded as a morphological manifestation of the hyperreaction of
      somatostatin-producing endocrine cells in the rat stomach to disorders in the
      internal environment of the body induced by impairment of renal parenchyma
      function.

PMID- 16601316
TI  - Peripheral mechanisms of intestinal dysmotility in the morphine tolerant and
      dependent rats.
AB  - Changes of intestinal motility and transit produced by tolerance to and
      dependence upon morphine have been partly attributed to peripheral mechanisms. We
      evaluated the effect of chronic peripheral morphine administration and peripheral
      mu-receptor blockade on vagal afferent activity (VAA) and c-Kit positive
      intramuscular cells of Cajal (ICCs). Ten rats were subjected to chronic
      subcutaneous morphine infusion for 72 h with subsequent VAA recording. Potential
      frequency was evaluated within recordings before and after mu receptor blockade
      by (D)-Phe -Cys -Tyr -(D)-Trp -Orn -Thr -Phe -Thr (CTOP) i.p. injections.
      Afterwards the rats were sacrificed and intramuscular c-Kit antigen expression
      was assessed by image analysis within removed fragments of duodenum and ascending
      colon. An equal group of rats served as a control for VAA and c-Kit expression.
      Analysis of VAA revealed similar frequencies of potentials in morphine tolerant /
      dependent rats before CTOP and in the controls. CTOP increased potential
      frequency in the morphine group which effect was visible mostly within the first
      20 minutes (p=0.01). The morphine infused animals presented also higher c-Kit
      expression in both the duodenum (p<0.001) and the ascending colon (p<0.001) in
      comparison to the control group. Results of our study may indicate the
      involvement of both the intestinal wall and the long vago-vagal reflexes in
      tolerance to and dependence upon opioids.

PMID- 16601317
TI  - Differences between properties of male and female motor units in the rat medial
      gastrocnemius muscle.
AB  - Differences between motor units in hindlimb locomotor muscles of male and female
      Wistar rats were studied. The contractile and action potential properties of
      various types of motor units as well as proportions of these units in the medial
      gastrocnemius muscle were analyzed. Experiments were based on functional
      isolation and electrical stimulation of axons of single motor units. Composition
      of motor units was different for male and female subjects, with higher number of
      the fast fatigable and lower number of slow type units in male animals. The
      contraction and the half-relaxation times were significantly longer in male motor
      units, what might be due to differences in muscle size. Slower contraction of
      male motor units likely corresponds to lower firing rates of their motoneurons.
      On the other hand, no significant differences between sexes were observed with
      respect to force parameters of motor units (the twitch and the maximum tetanus
      forces), except the fast resistant units (higher force values in male muscles).
      The mass of the muscle was approximately 1.5 time bigger in male rats. However,
      the mean ratio of motor unit tetanus force to the muscle mass was almost twice
      smaller in this group, what indirectly suggests that muscles of male rats are
      composed of higher number of motor units. Finally, female muscles appeared to
      have higher fatigue resistance as the effect of higher proportion of resistant
      units (slow and fast resistant) and higher values of the fatigue index in
      respective motor unit types. The motor unit action potentials in female rats had
      slightly lower amplitudes and shorter time parameters although this difference
      was significant only for fast resistant units.

PMID- 16601318
TI  - Leptin and long form of leptin receptor genes expression in the hypothalamus and
      pituitary during the luteal phase and early pregnancy in pigs.
AB  - Leptin is a polypeptide that plays a key role in the regulation of energy
      homeostasis and is also linked, among others, to mechanisms controlling
      reproductive processes. Data concerning the involvement of leptin in controlling
      reproductive functions at the level of hypothalamus and pituitary in the pig are
      limited. Therefore, in the present study, an expression of genes coding for
      leptin and long-form leptin receptor (Ob-Rb) was determined by a semiquantitative
      reverse transcription polymerase chain reaction (RT-PCR) in the discrete areas of
      porcine hypothalamus (medial basal hypothalamus - MBH, preoptic area - POA, stalk
      median eminence - SME) and pituitary (anterior - AP and posterior/neural - NP
      parts) during the luteal phase of the cycle (days 10-12 and 14-16) and two early
      stages of pregnancy (days 14-16 and 30-32). Leptin gene expression in MBH was
      found to be higher in the mid- than in the late-luteal phase, whereas in other
      structures studied it remained unchanged during these periods. More pronounced
      differences were noted in expression of Ob-Rb gene, which was increased in MBH,
      AP and NP during the late-luteal phase in comparison to the mid-luteal one,
      whilst the relationship in the POA was reversed. In turn, during pregnancy,
      leptin gene expression in all tested areas of hypothalamus as well as Ob-Rb mRNA
      content in MBH were higher on days 30-32 than on days 14-16. In contrast, in the
      anterior pituitary, Ob-Rb gene expression was more pronounced on days 14-16 than
      during later stage of pregnancy. Comparison of leptin and Ob-Rb mRNA content in
      studied structures between the mid-luteal phase and days 14-16 of pregnancy
      revealed inhibition of leptin gene expression in almost all examined tissues
      (MBH, POA, SME, NP) during early pregnancy whereas Ob-Rb gene expression was
      inhibited in POA but stimulated in both parts of the pituitary during this stage.
      In summary, obtained results suggest an involvement of leptin in the regulation
      of hypothalamic-pituitary axis activity during both the luteal phase of the cycle
      and early pregnancy in pigs.

PMID- 16601320
TI  - Molecular characterization and intracellular regulation of the human serotonin
      transporter in Caco-2 cells.
AB  - The serotonin transporter (SERT) has shown itself to be an effective
      pharmacological target in the treatment of mood disorders and some kinds of
      gastrointestinal syndromes. Most of the molecular studies of SERT in humans have
      been carried out using heterologous models. In this work, we have investigated
      the human enterocyte-like Caco-2 cell line as a potential "in vitro" model to
      study the human SERT. The results show that these cells express a SERT mRNA
      identical to the human brain SERT, and a 70 kDa protein immunodetected using a
      specific antibody. The SERT activity levels in Caco-2 cells increased in
      correlation with the onset and maintenance of the morphological and functional
      differentiation of the cells. Caco-2 SERT was also shown to be a high affinity
      (Kt=0.216 microM) saturable, Na(+) -dependent transporter that was inhibited by
      fluoxetine (IC(50)=17.6 nM). In addition, SERT activity was inhibited by the
      intracellular modulators protein kinase C and cAMP, either after short or long
      term treatment. In short, the expression and molecular characteristics of the
      human SERT in Caco-2 cells indicate that this cell line may be an ideal tool to
      study in vitro the physiology and pharmacology of human SERT.

PMID- 16601319
TI  - Inhibition of NOS-2 induction in LPS-stimulated J774.2 cells by 1, 5
      isoquinolinediol, an inhibitor of PARP.
AB  - Activation of both poly (ADP-ribose) polymerase (PARP) and inducible nitric oxide
      synthase (NOS-2) have been implicated in the pathogenesis of various forms of
      inflammation, therefore compounds which may simultaneously inhibit both pathways
      are of potential therapeutic interest. We tested the influence of potent
      inhibitor of PARP, 1, 5-isoquinolinediol (ISO), on NOS-2 induction in model of
      mouse macrophages (cell line J774.2) stimulated with lipopolysaccharide (1
      microg/ml). Pretreatment with ISO (1-300 microM) resulted in dose-dependent
      inhibition of accumulation of NOS-2-derived nitrite in culture medium (IC(50) =
      9,3 microM) as well as inhibition of NOS-2 protein induction in cultured J774.2
      cells; ISO given 10 hours after LPS did not influence activity of NOS-2.
      Interestingly, another PARP inhibitor, 3-aminobenzamide (3-AB, 10-3000 microM),
      did not influence 24-hr nitrite accumulation in J774.2 cell culture, either
      administered 15 minutes prior to LPS or 10 hrs after LPS. Scavenging of reactive
      oxygen species by use of mixture of SOD and catalase (SOD/Cat, 100/300 -
      1000/3000 U/ml) as well as cell permeable SOD-mimetic [Mn(III)TBAP, 1- 100
      microM], did not influence NOS-2 induction in J774.2 cells. In summary, we
      identified 1, 5-isoquinoline as potent inhibitor of induction of NOS-2 in LPS
      treated mouse macrophages. The exact mechanism of inhibitory action of this
      compound on NOS-2 induction requires further investigation.

PMID- 16601321
TI  - Influence of extracellular pH on the modulatory effect of zinc ions on Kv1.3
      potassium channels.
AB  - In the present study we applied the whole-cell patch-clamp technique to study the
      influence of extracellular pH (pH(o)) on the modulatory effect exerted by zinc
      ions (Zn(2+)) on voltage-gated potassium channels Kv1.3 expressed in human
      lymphocytes. Obtained data provide evidence that lowering of pH(o) from the 7.35
      to 6.4 slowed significantly the current activation rate, shifted the activation
      midpoint by about 16 mV towards positive membrane potentials and reduced the
      current amplitude to about 0.55 of the control value. In contrast, raising the
      pH(o) from 7.35 to 8.4 did not affect significantly the activation midpoint and
      current amplitude. Application of Zn(2+) in the concentration range from 100
      microM to 1 mM at pH(o)=6.4 slowed additionally the activation rate, shifted the
      activation midpoint by about 20 mV towards positive membrane potentials and
      reduced the current amplitude in a concentration-dependent manner. The total
      effect exerted by Zn(2+) and protons at pH(o) = 6.4 was more significant than the
      effect exerted by Zn alone. Both the magnitude of the shift and the degree of
      current inhibition by Zn(2+) were independent on pH(o) in the range from 6.4 to
      8.4. The data might suggest that the effects exerted by protons and zinc ions
      occur independently on each other and probably involve different mechanisms.
      Changing the holding potential from -90 mV to -60 mV at pH(o)=7.35 abolished the
      Zn(2+)-induced inhibition of the current amplitudes at concentrations below 300
      microM. At pH(o)=6.4 the total inhibition caused by Zn(2+) and protons was also
      diminished, however, a significant reduction was observed at 100 microM
      concentration. In contrast, changing the holding potential did not change the
      Zn(2+)- and proton-induced shift of the activation midpoint. Altogether, obtained
      data suggest that extracellular protons exert the modulatory effects that are
      additive to the effects exerted by Zn(2+) on the channels. Possible physiological
      significance of these additive effects is discussed.

PMID- 16601322
TI  - Influence of the "open field" exposure on calbindin D28K, calretinin, and
      parvalbumin containing cells in the rat midbrain - developmental study.
AB  - The aim of our study was to analyze the influence of the open field (OF) exposure
      on: 1. Distribution of c-Fos positive nuclei in: ventral tegmental area,
      substantia nigra, periaqueductal gray. 2. Appearance of calbindin-D28k,
      calretinin and parvalbumin in midbrain neurons that are engaged in the stress
      response. 3. Changes of c-Fos and calcium-binding proteins expression during
      maturation. The material consisted of Wistar rats of age between 0 and 90 days.
      The OF exposure was applied throughout 10 min and 90 min before the death of the
      animals. The brain sections were double stained using the antibodies against c
      Fos, CB, CR or PV. Our results showed that in all studied nuclei age-related
      increase of c-Fos expression (without changing of its distribution properties)
      was found. PV didn't show any co-localization with c-Fos in neurons of studied
      regions at any ages, however some PV-immunoreactive (PV-ir) basket-like
      structures around c-Fos-immunoreactive (c-Fos-ir) neurons were observed. In the
      youngest group of rats c-Fos-ir cells and cells immunoreactive for CB and CR
      constituted separate neuronal populations. During maturation increases in the
      level of their co-localization with c-Fos was observed. We may conclude that in
      adult rat midbrain structures CB-immunoreactive (CB-ir) and CR-immunoreactive (CR
      ir) cells (probably projection neurons) are mainly activated in the stress
      response following OF exposure. In the contrary PV-ir cells has only an indirect
      (modulatory) influence upon the c-Fos-ir cells.

PMID- 16601323
TI  - Macrophage colony-stimulating factor aggravates rather than regenerates
      emphysematous lungs in mice.
AB  - BACKGROUND: Lung regeneration is an innovative strategy that may cure pulmonary
      emphysema. The bone marrow (BM) harbors pulmonary stem cells. Hematopoietic
      cytokine-driven mobilization of BM cells may thus support lung regeneration.
      OBJECTIVES: The aim of this study was to determine whether systemic
      administration of macrophage colony-stimulating factor (M-CSF) leads to the
      regeneration of lungs in a murine model of elastase-induced emphysema. METHODS:
      C57BL/6J mice were administered elastase intratracheally. Four weeks later, in
      the absence or presence of elastase treatment, mice were intraperitoneally given
      either M-CSF or saline on days 1-5 each week for 3 weeks. Lung tissue was
      harvested 24 h after the last injection. RESULTS: M-CSF administration without
      prior elastase did not affect the mean linear intercept, surface area, or surface
      area/lung volume. In contrast, M-CSF administration following elastase injury
      caused a greater increase in the mean linear intercept and greater decreases in
      surface area and surface area/lung volume than saline administration following
      elastase, indicating that M-CSF aggravated emphysema. This aggravation of
      emphysema was accompanied by accumulation of pulmonary alveolar macrophages (AMs)
      expressing metalloproteinase (MMP)-9 and MMP-12. M-CSF stimulated AMs to express
      MMPs in vitro. CONCLUSIONS: These results suggest that M-CSF administration does
      not support lung regeneration but rather aggravates the lung destruction
      associated with elastase injury.

PMID- 16601324
TI  - The endocannabinoid system: A new player in the neurochemical control of
      vestibular function?
AB  - The results of recent clinical trials of medicinal cannabinoid drugs show that
      dizziness and vertigo are commonly reported adverse side-effects. Cannabinoid CB1
      receptors were initially thought to be expressed in very low densities in the
      vestibular nucleus complex (VNC). Recent immunohistochemical studies have
      challenged this idea and suggested that CB1 receptors may exist in numbers
      similar to the granule cell layer of the cerebellum. This, together with evidence
      that brainstem CB1 receptors have a higher efficacy than those in many other
      parts of the brain and that application of cannabinoids can elicit potent
      electrophysiological effects in VNC neurons, suggests that CB1 receptors and
      their endogenous ligands may be important in central vestibular function. In this
      review, we consider the potential clinical significance of the endocannabinoid
      system for the development of vestibular disorders, the effects of recreational
      cannabis use and the therapeutic use of medicinal cannabinoids.

PMID- 16601325
TI  - Liquid incubator with perfluorochemicals for extremely premature infants.
AB  - OBJECTIVES: Maintenance of appropriate body temperature, humidification and
      prevention of skin injury are very important in the management of extremely
      premature infants with immature skin. We have developed a new closed liquid
      incubator, utilising the characteristics of perfluorochemical (PFC) liquids,
      i.e., high specific gravity and chemical and biological inertness. The potential
      of this incubator to control body temperature was evaluated in rats. METHODS: PFC
      liquid (FC43; 3M Company, Tokyo, Japan) within the incubator was heated or cooled
      and the rectal temperature of each rat and the PFC temperature were monitored.
      RESULTS: The rectal temperature of rats floating on the PFC liquid surface
      changed almost in parallel to the temperature of PFC within the incubator,
      indicating that this technique can be used to warm or cool adults rats in a
      stable manner. The relative humidity of air within the incubator was maintained
      constant at 100%. CONCLUSIONS: The liquid incubator used in the present study
      maintained an environment with a relative humidity of 100% and allowed stable
      maintenance of temperature in adult rats. We also demonstrated that heating and
      cooling the PFC liquid allowed control of body temperature. Although further
      studies are required, this new incubator may be useful for the clinical
      management of extremely premature infants.

PMID- 16601326
TI  - C-reactive protein predicts vascular access thrombosis in hemodialysis patients.
AB  - BACKGROUND: Vascular access thrombosis (VAT) is one of the most common morbidity
      in hemodialysis patients. The development of arteriovenous fistula thrombosis is
      associated with vascular intimal hyperplasia. Some studies suggested that serum C
      reactive protein (CRP) predicts the development of vascular intima hyperplasia
      that conduces vascular access stenosis and thrombosis. This study aimed to access
      the clinical usefulness of CRP in predicting VAT in hemodialysis patients.
      METHODS: We retrospectively reviewed all prevalent hemodialysis patients with
      native arteriovenous fistula (nAVF) between November 2001 and November 2004. The
      CRP levels and relation to the development of VAT was analyzed with Kaplan-Meier
      analysis in four groups of patients divided according to their serum CRP levels.
      Besides serum CRP levels, other factors possibly influencing vascular access
      thrombosis were also considered: gender, age, diabetes, aspirin, smoking, statin,
      serum albumin, hematocrit, cholesterol > 200 mg/dl, Calcium-phosphate product,
      and intact parathyroid hormone > 200 pg/ml. RESULTS: We retrospectively reviewed
      223 chronic hemodialysis patients. 198 patients with forearm nAVF and 25 with
      upper arm nAVF were included. Of the above 223 patients, 51 experienced one or
      more VAT episodes. In Kaplan-Meier survival analysis, patients with serum CRP
      levels > 0.8 mg/dl were prone to develop VAT (log-rank, p < 0.001). In a
      multivariate Cox regression model, serum CRP greater than 0.8 mg/dl was confirmed
      to be an independent predictor of VAT with a relative risk of 16.6 times (95% CI,
      7.85-35.1). The area under the receiver operator characteristic (ROC) curve of
      CRP > 0.8 mg/dl in predicting VAT events is 0.785 (95% CI, 0.712-0.858; p <
      0.001). Sensitivity and specificity of CRP (> 0.8 mg/dl) in predicting VAT were
      80.4 and 72.7%. CONCLUSIONS: The serum CRP levels not only predict cardiovascular
      disease and mortality in hemodialysis patients but also predict the development
      of vascular access thrombosis in chronic hemodialysis patients.

PMID- 16601327
TI  - Elevated troponin levels after prolonged supraventricular tachycardia in patient
      with normal coronary angiography.
AB  - The European Society of Cardiology and the American College of Cardiology
      redefined the concept of myocardial infarction in the presence of highly positive
      markers of myocardial injury associated with at least one of the following:
      ischemic symptoms; development of pathologic Q waves on the ECG or ECG changes
      indicative of ischemia (positive or negative deviation of the ST segment), making
      troponins one of the most important aspects in the evaluation and stratification
      of patients with chest pain in the emergency room. However, although troponin
      gives excellent accuracy in the identification of myocardial necrosis, it is
      known that it can also be elevated in a series of nonatherosclerotic heart
      diseases. We present the case of a 49-year-old female patient admitted to the
      Chest Pain Unit with a history of supraventricular tachycardia associated with
      chest discomfort, nausea and diaphoresis. During risk stratification, the patient
      presented with a high serum troponin T level (0.143 ng/ml) but with a normal
      coronary angiography.

PMID- 16601328
TI  - Association between electrocardiographic left ventricular hypertrophy with strain
      pattern and left ventricular structure and function.
AB  - BACKGROUND AND PURPOSE: Electrocardiographic left ventricular hypertrophy (LVH)
      with strain pattern has been documented as a marker for LVH. Its presence on the
      ECG of hypertensive patients is associated with poor prognosis. The study was
      carried out to assess the association of the electrocardiographic strain with
      left ventricular mass (LVM) and function in hypertensive Nigerians. MATERIAL AND
      METHODS: ECG as well as echocardiograms were performed in 64 hypertensive
      patients with ECG-LVH and strain pattern, 65 patients with ECG-LVH by Sokolow
      Lyon (SL) voltage criteria and 62 normal controls. RESULTS: The study showed that
      electrocardiographic left ventricular (LV) strain pattern is associated with
      dilated left atrium, larger LV internal dimensions and greater absolute and
      indexed LVM in hypertensive Nigerians compared with ECG-LVH by SL voltage
      criteria alone or normal controls. CONCLUSION: The findings of this study support
      the fact that the ECG strain pattern is associated with increased LVM and an
      increased risk of developing abnormal LV geometry.

PMID- 16601329
TI  - Evolution of cognitive deficits and conversion to dementia in patients with mild
      cognitive impairment: a very-long-term follow-up study.
AB  - Ten patients with mild cognitive impairment (MCI) underwent extensive
      neuropsychological evaluation at 12-monthly intervals for a minimum of 6 years.
      All 10 patients declined and 5 have now died. The onset of dementia, as defined
      by a fall in global cognitive function (MMSE <24) or activities of daily living
      (Clinical Dementia Rating Scale; CDR) ranged from 1 to 8 years with generally
      good concordance between these measures. The rate of decline on the MMSE was
      highly variable ranging from 0.86 to 2.83 points per year. Other than a
      consistent impairment on tests of episodic memory and category fluency (8 out of
      10), other early cognitive deficits were difficult to define and tended to be
      unstable in the early stages. Impairment of semantic memory, visuo-spatial and
      attentional abilities eventually developed but the sequence of deficit
      acquisition was heterogeneous. These findings are discussed in the light of
      current views of MCI. Amnestic MCI may not be an accurate concept unless semantic
      memory impairment is also considered as an integral core deficit. Full-blown
      dementia may take many years to develop in patients with MCI but was a universal
      feature in this study.

PMID- 16601330
TI  - Lentiviral-mediated fetal gene therapy for monogenic disorders: development of an
      in vitro rabbit model.
AB  - OBJECTIVE: Fetal gene replacement is a novel, potential therapy for monogenic
      disorders which are diagnosed prenatally. The purpose of this study was to
      develop in vitro, respiratory-epithelium targeted, lentiviral (LV)-mediated gene
      transfer in fetal rabbit tracheas. METHODS: Via triple plasmid transfection,
      vesicular stomatitis virus-G (VSV-G)-pseudotyped LV vector containing green
      fluorescent protein (GFP) marker gene, under the control of a cytomegalovirus
      promoter was constructed. LV bioavailability in rabbit amniotic fluid (AF) was
      evaluated by infectivity assays of 293T cell monolayers in variable
      concentrations of AF. Fetal tracheas from time-mated rabbits (term gestation, G =
      31 days) were collected on G 23-25 days, and placed in tissue culture (substrate
      enriched DMEM, 37 degrees C, 5% CO(2)/room air). The tracheal cultures were
      transfected with 1 x 10(5) LV particles, and analyzed daily for: reporter gene by
      polymerase chain reaction, and reporter gene product (GFP) by whole-mount
      fluoroscopy and immunohistochemistry. RESULTS: 293T cell infectivity assays
      confirmed bioavailability of LV in rabbit AF. Following in vitro transfection,
      GFP DNA and GFP were detectable in fetal rabbit tracheas by 4 and 5 days,
      respectively. Immunocytochemistry localized GFP to the luminal aspect of tracheal
      epithelium. CONCLUSIONS: In vitro, LV-mediated GFP gene transfer to fetal rabbit
      tracheas occurs within 4 days, and gene expression is evident by 5 days post
      transfection. This observation, and the bioavailability of LV through AF,
      suggests the appropriateness of this model for the future evaluation of in vivo,
      transamniotic gene delivery strategies.

PMID- 16601331
TI  - Minimal alteration in the ratio of circulatory fetal DNA to fetal corticotropin
      releasing hormone mRNA level in preeclampsia.
AB  - OBJECTIVES: We have recently observed that fetal DNA and fetal corticotropin
      releasing hormone (CRH) mRNA are associated with in vitro generated
      syncytiotrophoblast-derived microparticles, and that the ratio of fetal DNA to
      mRNA (CRH) varied according to whether the particles were derived by
      predominantly apoptotic, apo-necrotic or necrotic pathways. Hence, we examined
      whether these ratios varied in maternal plasma samples taken from normotensive
      and preeclamptic pregnancies in vivo. METHODS: Maternal plasma samples were
      collected from 18 cases with preeclampsia and 29 normotensive term controls.
      Circulatory fetal CRH mRNA and DNA levels were quantified by real-time PCR and RT
      PCR. RESULTS: Circulatory fetal mRNA and fetal DNA levels were significantly
      elevated in the preeclampsia study group when compared to normotensive controls.
      Alterations in the fetal mRNA to DNA ratio between the study and control groups
      were minimal, even when stratified into early (<34 weeks of gestation) and late
      (>34 weeks of gestation) onset preeclampsia. CONCLUSIONS: Our data suggest that
      although circulatory fetal DNA and mRNA levels are significantly elevated in
      preeclampsia, the ratios in maternal plasma are not dramatically altered.

PMID- 16601332
TI  - Recurrent fetal hydrops due to mucopolysaccharidoses type VII.
AB  - Hydrops fetalis is associated with a wide range of abnormalities. In about 20% of
      cases of non-immune fetal hydrops, no cause is found despite investigations
      including routine post-mortem examination and enzyme studies may be indicated to
      detect an underlying metabolic storage disease. Fetal hydrops due to
      mucopolysaccharidosis type VII is very rare and a prenatal diagnosis is not
      usually made. We report a case of mucopolysaccharidosis type VII presenting as
      recurrent fetal hydrops and review the clinico-pathological features of this
      disorder.

PMID- 16601333
TI  - Endoscopic release of limb constriction rings in utero.
AB  - Amniotic band syndrome is a sporadic condition that may result in constriction
      bands, amputation and multiple craniofacial, visceral and body wall defects. It
      occurs in 1/1,200 to 1/15,000 live births. Most cases present with multiple
      congenital anomalies that are incompatible with life. A small group of fetuses
      shows isolated limb constrictions that may cause severe limb dysfunction or limb
      amputation if left untreated. Successful in utero surgical lyses of constriction
      rings have been reported. We report a case of constriction amniotic bands
      involving both legs and compromising blood flow to the distal extremity. The
      constriction ring was successfully released by a minimally invasive endoscopic
      surgical technique avoiding severe limb dysfunction or foot amputation.

PMID- 16601334
TI  - Sildenafil citrate and fetal outcome in pregnant rats.
AB  - OBJECTIVE: To determine the effects of sildenafil citrate on fetal growth in
      maternal rats exposed to hypoxia. METHODS: Timed pregnant rats were randomized to
      either hypoxia or control on gestational days (GD) 18-20, and received either
      sildenafil (45 mg/kg) orally every 12 h on GD 18-21 or an equal volume of sterile
      water. Fetal pups were retrieved by laparotomy on GD 21. Pup weight and length
      were evaluated and cGMP measured in maternal and fetal blood. RESULTS: In the non
      hypoxic rats, sildenafil exposure was associated with a decrease in size(4.75 +/-
      0.43 vs. 5.11 +/- 0.34 g, p = 0.00). In contrast, in the hypoxic rat model,
      sildenafil exposure was associated with increased size of the offspring (5.48 +/-
      0.45 vs. 5.16 +/- 0.36 g, p = 0.016). Maternal cGMP levels were increased in the
      presence of both sildenafil and hypoxia (23.0 +/- 10.5 vs. 15.6 +/- 2.7 pmol/ml,
      p = 0.001). CONCLUSION: Exposure to sildenafil in a non-hypoxic setting results
      in a decrease in fetal size. Sildenafil in the presence of a stimulus, hypoxia,
      will lead to increased fetal size. These results suggest that sildenafil may have
      some influence on fetal growth. How these effects occur and by what mechanism
      remain to be determined.

PMID- 16601335
TI  - Screening for trisomy 21 with maternal age, fetal nuchal translucency and
      maternal serum biochemistry at 11-14 weeks: a regional experience from Germany.
AB  - OBJECTIVE: To examine the efficacy of first trimester screening for trisomy 21
      using a combination of maternal age, fetal nuchal translucency (NT), maternal
      serum free beta-human chorionic gonadotropin (free beta-hCG) and pregnancy
      associated plasma protein A (PAPP-A) in a regional setting [maternity unit of the
      Women's University Hospital, Hannover Medical School (study center); two regional
      private centers for prenatal diagnosis and human genetics; laboratory for
      prenatal diagnosis and human genetics]. METHODS: Fetal NT, crown-rump length,
      maternal serum free beta-hCG and PAPP-A were measured at 11-14 weeks of
      gestation. Risk calculation was carried out using the FMF computer algorithm. The
      patients were informed and counseled about possible invasive test options if the
      risk was 1 in 300 or greater. Fetal outcome was obtained by questionnaires given
      to the patients or sent to their gynecologists. The detection and false-positive
      rates for the different screening strategies were calculated. RESULTS: Pregnancy
      outcome was obtained in 2,497 cases, of which 2,196 cases had completed first
      trimester screening with NT and maternal serum biochemistry and 301 additional
      cases had NT measurement only. The median age was 32.5 years. In our population
      11 affected fetuses were found. The estimated risk for trisomy 21 was 1 in 300 or
      greater in 64, 82, 88 and 88% of affected fetuses using maternal age alone, in
      combination with nuchal translucency, with maternal serum biochemical markers or
      with both NT and biochemical markers for a false-positive rate of 28.2, 5.1, 15.3
      and 4.0%. CONCLUSIONS: First trimester screening using maternal age, NT, free
      beta-hCG and PAPP-A is highly effective for the detection of trisomy 21 and is
      associated with a sensitivity of about 90% for 5% false-positive patients.

PMID- 16601336
TI  - Successful treatment of extremely severe fetal anemia due to anti-Jra
      alloimmunization.
AB  - BACKGROUND: Although Jr(a) hemolytic disease of the newborn (HDN) is generally
      considered to be mild, we encountered a case of anti-Jr(a) alloimmunization
      hydrops fetalis due to extremely severe fetal anemia that required aggressive
      intrauterine treatment. CASE REPORT: A Japanese woman developed hydrops fetalis
      at the 29th week of gestation. Blood examination was highly positive for anti
      Jr(a) antibodies. Cordocentesis demonstrated that the fetus had anti-Jr(a)
      antibodies and the lowest fetal hemoglobin concentration was 2.3 g/dl. After a
      total of four intravascular transfusions, fetal hydrops improved and a healthy
      girl of 2,120 g was delivered at the 35th week of gestation. The initial neonatal
      hemoglobin concentration at birth was 7.2 g/dl. After two straight transfusions,
      the infant's anemia did not worsen. Anti-Jr(a) antibodies became negative without
      developing hyperbilirubinemia. CONCLUSION: The incidence of Jr(a) negativity can
      lead to underestimation of the risk of Jr(a) alloimmunization. This case shows
      that anti-Jr(a) alloimmunization may cause HDN and hydrops fetalis.

PMID- 16601337
TI  - An audit of outcome in intravascular transfusions using the intrahepatic portion
      of the fetal umbilical vein compared to cordocentesis.
AB  - INTRODUCTION: Maternal red cell alloimmunization is a potential cause of
      perinatal morbidity and mortality. The outcome of severe disease has been
      transformed by the use of in-utero and particularly, fetal intravascular
      transfusion. In the majority of instances this is performed by cordocentesis.
      However, this cohort study represents the experience in a large tertiary referral
      centre in performing fetal intravascular transfusions via the intrahepatic vein
      (IHV). METHODS: Over an 8-year period, 1997-2004, 221 in-utero transfusions (IUT)
      were performed for rhesus disease in 66 pregnancies. 86% had severe fetal anaemia
      caused by anti-D, 10.6% by anti-Kell and 3.4% by anti-c. The median maternal age
      of the cohort was 31 years (range 19-43). The median gestation at initial IUT was
      25 weeks (interquartile range (IQR) 23-29 weeks). RESULTS: A median number of
      three IUT were performed in each fetus (IQR 2-5) with a median haemoglobin at
      first fetal blood sampling of 7.3 g% (IQR 4.6-8.8 g%) (73% < or =5 SD and 27% <
      or =2 SD). Of the total intravascular transfusions, 170 were performed via the
      IHV (71.7%), 33 via cordocentesis (13.9%) and 1 by intracardiac puncture (0.5%).
      There were 'transient' bradycardias complicating 4.1% of all transfusions and
      amniorrhexis following 1.4%. 92% of babies were live born at a median gestation
      of 34 weeks (range 21-38) with a birth weight centile of 50 (range 3-90). There
      was no significant difference in intravascular transfusion complication rate when
      the procedure was performed via the IHV (7.6%) as compared to cord root puncture
      (3.0%) (Fisher's exact test, p < 0.47). CONCLUSION: IUT performed by fetal IHV
      puncture is safe and carries no excess morbidity when performed for severe rhesus
      disease.

PMID- 16601338
TI  - Successful treatment of post-cesarean hemorrhage related to placenta praevia
      using an intrauterine balloon. Two case reports.
AB  - The authors report a positive experience in controlling severe postpartum
      hemorrhage after cesarean section performed for placenta praevia by using an
      inflated intrauterine balloon and avoiding any further invasive surgery.

PMID- 16601339
TI  - Inherited thrombophilia: treatment during pregnancy.
AB  - OBJECTIVE: Inherited thrombophilia is associated with thromboembolic events
      and/or poor obstetric outcome. We evaluated the pregnancy outcome in women with
      inherited thrombophilia treated with low-molecular-weight heparin (LMWH).
      METHODS: 38 thrombophilic women with a history of thromboembolic events and/or
      poor obstetric outcome were treated during their 39 consecutive pregnancies with
      LMWH from pregnancy verification until 4-6 weeks in puerperium. A fixed dose of
      enoxaparin 4,000 IU/day (except 1 case who required nadroparin 0.3 ml/day) was
      administered in most cases, adopting a higher dose (6,000 IU/day to 6,000 IU
      twice a day) in those with previous thromboembolic events. RESULTS: In the
      treated women, all had a good obstetric outcome, whereas in the previous
      untreated pregnancies (n = 78), the rate of fetal loss (early and late) was
      76.9%, only 12 live infants survived (66.6%). Moreover, birth weight resulted
      significantly higher in live infants born to treated pregnancies in comparison to
      that of previous untreated pregnancies (p = 0.009). No maternal thrombosis or
      major bleeding complications were recorded. CONCLUSIONS: The treatment with LMWH
      improved pregnancy outcome resulting effective and safe in thrombophilic women
      with a history of thromboembolic events and/or poor obstetric outcome.

PMID- 16601340
TI  - Solutes in maternal circulation and gestational sac compartments during early
      human development.
AB  - OBJECTIVES: The aim of this study was to review previous work reporting the
      concentration of solutes measured in maternal circulation, extra-embryonic
      celomic fluid, and amniotic fluid, to gain insights into the mechanism that could
      lead to compartmentalization of fluid and solutes within the gestational sac
      prior to the 12th week of pregnancy. METHODS: We conducted a Medline and PubMed
      literature search from January 1990 through March 2004 using the key words
      amniotic fluid, celomic fluid, coelomic fluid, celocentesis, coelocentesis,
      amniocentesis, yolk sac and embryonic cavities. We selected those articles
      describing solutes that had been measured in the same patient in samples obtained
      prior to 12 weeks' gestation from maternal circulation, celomic fluid and
      amniotic fluid. Information extracted from these publications included:
      gestational age at sampling, number of samples evaluated, mean concentration of
      the solutes in each of the three fluids and bibliographic citation. RESULTS: We
      found 73 publications with the key words and selected 13 that met the inclusion
      criteria. The concentration of 31 solutes reported in each of the three
      compartments was documented and gradients among compartmental interfaces
      calculated. CONCLUSION: This study describes the concentration of solutes
      measured in maternal circulation, extracelomic fluid and amniotic fluid early in
      human development. Analysis of calculated gradients across the compartmental
      interfaces suggests that the shift of fluid may depend on the biophysical
      properties of the placenta and yolk sac and on graded changes in hydrostatic
      pressures across compartments.

PMID- 16601341
TI  - West Nile virus during pregnancy: a case study of early second trimester maternal
      infection.
AB  - A woman who contracted West Nile virus (WNV) neuroinvasive illness during her
      second trimester subsequently elected to terminate her pregnancy due to concerns
      of possible adverse effects of WNV on her developing fetus. Consent was obtained
      to test maternal and post-mortem fetal tissues for WNV infection. Fetal blood,
      liver, kidneys, spleen, umbilicus and amniotic fluid were negative for WNV RNA by
      polymerase chain reaction and negative for WNV IgM antibodies by ELISA,
      indicating that in this case there was no evidence of WNV transmission to the
      fetus. Until further information regarding outcomes of WNV infection during
      pregnancy is available, pregnant women in areas where WNV is transmitted should
      take precautions to avoid mosquito bites. Women with WNV illness during pregnancy
      should undergo regular prenatal checkups including ultrasound examinations to
      assess fetal development, and healthcare providers should promptly report cases
      of WNV in pregnant women to their state or local health department or to CDC.

PMID- 16601343
TI  - Hypothesis: the placental 'steal' phenomenon - a possible hazard of
      amnioreduction.
AB  - The twin-twin transfusion syndrome (TTTS) complicates approximately 15% of
      monochorionic twin pregnancies. Severe TTTS is associated with poor neonatal
      outcome and a relatively high rate of neurological abnormalities. Some studies
      have suggested this outcome to be more severe in cases treated by amnioreduction.
      In this paper we present a hypothesis that radical amnioreduction performed after
      24 weeks of gestation might cause a shift of blood from the fetus into the
      placenta. This could explain some of the severe neurological outcomes, such as
      hypoxic ischemic brain damage, seen in these cases.

PMID- 16601342
TI  - Prenatal ultrasound diagnosis, follow-up, and outcome of congenital varicella
      syndrome.
AB  - OBJECTIVES: To report on a case of fetal varicella infection following the
      diagnosis of maternal infection at 16 weeks of gestation. METHODS: Diagnosis was
      based on serology testing and prenatal ultrasound, confirmed by DNA detection in
      amniotic fluid (Lightcycler-PCR). Serial ultrasound examinations were performed.
      RESULTS: Sonographic anomalies included borderline ventriculomegaly,
      intracerebral, intrahepatic and myocardial calcifications, limb deformities,
      articular effusions, and intrauterine growth retardation (confirmed
      postpartally). The newborn showed a severe encephalopathy and could not be
      stabilized sufficiently. The child died 23 days after birth. CONCLUSION: The
      outcome of an affected fetus may be very serious and prenatal ultrasound is a
      helpful tool to recognize the severity of the infection.

PMID- 16601344
TI  - Conduction system disease in fetuses evaluated for irregular cardiac rhythm.
AB  - OBJECTIVES: To determine the prevalence of 1st and 2nd degree AV block in fetuses
      with an irregular cardiac rhythm, and to summarize outcome of these pregnancies.
      BACKGROUND: The diagnosis of irregular cardiac rhythm or 'skipped beats' includes
      isolated ectopy that resolves spontaneously. Recently, Doppler measurements of
      the 'mechanical' PR interval have been shown to identify AV conduction disease
      prenatally. Prenatal therapy of these conduction abnormalities may limit the
      progression to more advanced disease either in utero or after birth. METHODS: A
      retrospective review was performed of fetuses evaluated between 1996 and 2004
      with the findings of irregular cardiac rhythm. 1st or 2nd degree AV block was
      diagnosed on Doppler and M-mode recordings, and confirmed using either fetal
      magnetocardiography (fMCG) or postnatal 12-lead ECG. Dexamethasone was
      administered to 4 mothers with abnormal fetal AV conduction in the setting of
      anti-Ro/anti-La antibodies. RESULTS: Of 702 fetuses initially referred for
      arrhythmia, 306 had an irregular rhythm. Eight (2.6%) had intermittent 1st or 2nd
      degree AV block confirmed by fMCG and/or postnatal 12-lead ECG. AV block was
      presumed idiopathic in 2, associated with congenital long QT syndrome in 2 or
      with clinically unsuspected maternal anti-Ro or anti-La antibodies in 4. During
      the intrauterine period there was no progression to complete AV block and all
      were born alive at 34-40 weeks of gestation. CONCLUSION: A small but clinically
      significant population of fetuses with irregular rhythm will have 1st or 2nd
      degree AV block. Transplacental therapy may limit the intrauterine progression to
      more advanced disease.

PMID- 16601345
TI  - Encouraging early clinical experience with deliberately delayed temporary
      fetoscopic tracheal occlusion for the prenatal treatment of life-threatening
      right and left congenital diaphragmatic hernias.
AB  - OBJECTIVE: In order to assess the effect of deliberately delayed percutaneous
      fetoscopic tracheal occlusion on survival of fetuses with life-threatening
      congenital diaphragmatic hernia. METHODS: Eight fetuses with life-threatening
      congenital diaphragmatic hernia underwent fetoscopic tracheal balloon occlusion
      between 29 + 0 and 32 + 4 weeks of gestation. Delayed occlusion was chosen in
      order to minimize potentially negative pulmonary effects from premature delivery
      as a result of fetal surgery. In addition, we wanted to become able to provide
      all available postnatal intensive care treatment means in these patients.
      RESULTS: Six of the 8 fetuses survived to discharge from hospital. CONCLUSION:
      Delayed fetoscopic tracheal balloon occlusion may be rewarded with lung growth
      sufficient to allow survival of fetuses with life-threatening congenital
      diaphragmatic hernia.

PMID- 16601346
TI  - Very rare congenital malformations: responsibilities of scientists. The case of
      rachipagus conjoined twins.

PMID- 16601347
TI  - The effect of imatinib mesylate on the contractility of isolated rabbit
      myometrial strips.
AB  - BACKGROUND: C-kit receptor expressing interstitial cells generate and coordinate
      the electrical signals that control peristalsis in the gut. However, the function
      of interstitial cells in the myometrium is not known. METHODS: (1) Sections of
      rabbit myometrium were subjected to immunohistochemical staining for the c-kit
      receptor. (2) Spontaneously contracting myometrial strips from New Zealand White
      rabbits near term were mounted in an organ bath and attached to a tension
      recording device. The effect of increased concentrations of the c-kit receptor
      antagonist imatinib mesylate on these contractions was observed. The main outcome
      measures were the change in frequency, amplitude and duration of contraction.
      RESULTS: (1) Multipolar cells expressing c-kit were identified in the
      fibromuscular septum confirming the presence of interstitial cells in rabbit
      myometrium. (2) Imatinib decreased the amplitude of contractions by approximately
      20% at 100 microM. No effect was seen at lower concentrations. No effect of
      imatinib on frequency or duration of contractions was observed at any of the
      concentrations studied. CONCLUSIONS: In isolated rabbit myometrium, acute
      inhibition of the c-kit receptor by imatinib mesylate affects only the amplitude
      of spontaneous contractions at concentrations, the equivalent of x10-100 the
      normal therapeutic concentration.

PMID- 16601348
TI  - Increased aortic intima-media thickness is related to lipid profile in newborns
      with intrauterine growth restriction.
AB  - BACKGROUND AND AIM: Low birth-weight is known to be associated with an increase
      in cardiovascular risk similar to that seen with major environmental risk
      factors, such as cigarette smoking or hypertension. Much epidemiological evidence
      has linked low birth-weight with hypertriglyceridaemia. METHOD: We measured
      aortic wall thickness by ultrasonography and lipid profile in 40 newborn babies
      with intrauterine growth restriction and 40 controls. RESULTS: Maximum and mean
      aortic intima-media thickness were significantly higher in the babies with
      intrauterine growth retardation (0.58 +/- 0.06, 0.52 +/- 0.03 mm, respectively)
      than in controls (0.44 +/- 0.05, 0.40 +/- 0.03 mm, p < 0.0001, p < 0.0001,
      respectively), more so after adjustment for birth-weight (maximum intima-media
      thickness: 0.23 +/- 0.03 mm/kg vs. 0.12 +/- 0.02 mm/kg, p < 0.0001; mean intima
      media thickness: 0.21 +/- 0.02 mm/kg vs. 0.11 +/- 0.01 mm/kg, p < 0.0001). Serum
      triglyceride levels were significantly higher in the intrauterine growth
      retardation group (48.9 +/- 14.8 mg/dl) compared with the control group (32.5 +/-
      9.8 mg/dl, p < 0.0001). The mean body mass index, prepregnancy weight, weight
      gain during pregnancy, maternal LDL cholesterol level and, height of the mothers
      were significantly lower in the intrauterine growth retardation group compared
      with the control group. For maximum aIMT, significant associations included the
      ponderal index (p = <0.01), length (p = 0.01) and serum triglyceride levels of
      infants (p = 0.02). CONCLUSION: Newborn babies with growth restriction have
      significant maximum aortic thickening with hypertriglyceridaemia, suggesting that
      prenatal events might predispose to later cardiovascular risk.

PMID- 16601349
TI  - Sensitization to Lolium multiflorum grass pollen in pollinosis patients:
      evaluation of allergenic fractions recognized by specific IgE antibodies.
AB  - BACKGROUND: Lolium multiflorum (Lm) pollen allergens are the major causative
      agents for rhinoconjunctivitis in Southern Brazil. There have been no studies
      about the sensitization and allergenic cross-reactivity between Lm and other
      grass pollens. We evaluated the sensitization of Brazilian pollinosis patients to
      Lm pollen allergens through skin prick test (SPT) and immunoassays (ELISA and
      immunoblot). METHODS: Serum samples from 60 patients with pollinosis and positive
      SPT to grass pollen extracts (Lm+ group), 30 patients with negative SPT to grass
      pollen, but positive SPT to mite extracts (Lm- group), and 30 nonatopic subjects
      (NA group) were tested by SPT, ELISA, and immunoblot using Lm extract. Inhibition
      immunoassays with Lolium perenne (Lp), mixed grass (Gmix) and Lm extracts were
      also performed. RESULTS: A high concordance was found between the Gmix and Lm
      extracts in SPT. Positivity rates in SPT were also highly concordant with IgE
      ELISA results. The assay was able to detect Lm-specific IgE in >95% of Lm+
      patients. A significant self- and cross-inhibition was observed in IgE-ELISA,
      reflecting a high cross-reactivity between the grass pollen allergens. Immunoblot
      revealed 13 IgE-binding Lm fractions, from which the bands 28-30 kDa and 31-34
      kDa were recognized by >90% of Lm+ patients. CONCLUSION: Lm-specific IgE
      antibodies are highly cross-reactive with pollen proteins from other grass
      species. The results indicate that Lm extracts could be used in both SPT and
      ELISA for a more specific evaluation of IgE responses to Lm grass pollen in
      Brazilian pollinosis patients.

PMID- 16601351
TI  - Enhanced frequency of CD18- and CD49b-expressing T cells in peripheral blood of
      asthmatic patients correlates with disease severity.
AB  - BACKGROUND: Results from a transcriptome analysis of human CD4+ T regulatory type
      1 (Tr1) clones have indicated that transcripts for the integrins CD18 and CD49b
      are overexpressed in these cells. The aim of this study was to investigate
      whether the presence of T cells concomitantly expressing these molecules could be
      detected in asthmatic patients and represent Tr1 cells. METHODS: Expression of
      CD18 and CD49b was analyzed by flow cytometry on peripheral blood mononuclear
      cells from asthmatic patients of various severity and healthy subjects. The
      cytokine production profile of purified CD4+ CD18(high) CD49b+ T cells was
      analyzed by ELISA. The effect of glucocorticoid treatment on the expression of
      CD18 and CD49b was determined. RESULTS: The frequency of peripheral blood
      CD18(high) CD49b+ T cells was significantly elevated in severe asthmatic
      patients, as compared with both mild asthmatic and healthy donors, and was
      diminished in asthmatic patients with a controlled status of the disease. Neither
      short-course oral glucocorticoid treatment of asthmatic patients ex vivo, nor
      culture of their peripheral blood mononuclear cells with dexamethasone in vitro,
      increased the frequency of CD18(high) CD49b+ T cells, indicating that their
      presence seems to be independent from recent anti-inflammatory treatment.
      However, purified CD4+ CD18(high) CD49b+ T cells from these patients, in contrast
      to those from healthy donors, lacked the production of the immunosuppressive
      cytokine interleukin-10. CONCLUSION: In contrast to healthy donors, peripheral
      blood CD18(high) CD49b+ T cells of asthmatic patients do not fulfill the
      phenotypic criteria of Tr1 cells. Nevertheless, the presence of elevated numbers
      of peripheral blood CD18(high) CD49b+ T cells is characteristic for patients with
      severe and uncontrolled asthma.

PMID- 16601350
TI  - Variability of Ole e 9 allergen in olive pollen extracts: relevance of minor
      allergens in immunotherapy treatments.
AB  - BACKGROUND: Clustered severe adverse reactions to immunotherapy with olive pollen
      extracts have been occasionally reported in areas where olive trees are
      extensively grown. Allergic patients from these areas, in addition to the major
      olive pollen allergen Ole e 1, frequently recognize a recently described
      allergen, Ole e 9. OBJECTIVE: We aimed to develop an immunoassay to measure Ole e
      9 concentration and to study the variability of this allergen in olive pollen
      extracts. METHODS: Monoclonal antibodies (mAb) to Ole e 9 were produced from mice
      immunized with the pure allergen. One of these mAbs was used to develop a
      sandwich ELISA with an anti-olive pollen extract rabbit serum as the tracer.
      Olive pollen batches from several suppliers were analyzed using this method.
      These batches were also analyzed for Ole e 1 content and biological activity.
      RESULTS: A 10-fold variation between the extreme values was found for the
      biological activity of the batches analyzed. Ole e 1 concentration showed a 25
      fold variation. Variability of Ole e 9 concentration was extremely high, up to
      161 times. The ratio Ole e 1/Ole e 9 varied in a range from 0.6 to 390.4.
      CONCLUSION: The availability of a mAb-based ELISA for Ole e 9 made it possible
      for us to detect an important source of variability in olive pollen batches. This
      variability may be the cause of outbreaks of adverse reactions in the course of
      immunotherapy treatments, which have sometimes been observed among olive-allergic
      patients living in areas with very high levels of airborne olive pollen.

PMID- 16601352
TI  - Luteolin, a flavonoid, inhibits CD40 ligand expression by activated human
      basophils.
AB  - BACKGROUND: We have previously shown that flavonoids such as luteolin, apigenin
      and fisetin inhibit interleukin 4 and interleukin 13 production. In this study,
      we investigated whether luteolin can suppress CD40 ligand expression by
      basophils. METHODS: A human basophilic cell line, KU812, was stimulated with
      A23187 and phorbol myristate acetate (PMA) with or without various concentrations
      of luteolin or other flavonoids for 12 h, and CD40 ligand expression was analyzed
      by FACS. The effect of luteolin on CD40 ligand mRNA expression was studied by
      semiquantitative reverse transcription PCR analysis. In addition, CD40 ligand
      expression was also measured in purified basophils that had been stimulated for
      12 h with A23187 plus PMA with or without various concentrations of luteolin.
      RESULTS: CD40 ligand expression by KU812 cells was enhanced noticeably in
      response to A23187 and even more strikingly augmented by A23187 plus PMA. The
      expression was significantly suppressed by 10 or 30 microM of luteolin, whereas
      myricetin failed to inhibit. Reverse transcription PCR analyses demonstrated that
      luteolin inhibited CD40 ligand mRNA expression by stimulated KU812 cells. Of the
      six flavonoids examined, luteolin, apigenin, fisetin and quercetin at 30 microM
      showed a significant inhibitory effect on CD40 ligand expression. The incubation
      of purified basophils with A23187 plus PMA significantly enhanced CD40 ligand
      expression, and the presence of luteolin again had an inhibitory effect.
      CONCLUSIONS: Luteolin inhibits CD40 ligand expression by activated basophils.

PMID- 16601353
TI  - Distinct pattern of commensal gut microbiota in toddlers with eczema.
AB  - BACKGROUND: Recent studies have demonstrated differences in the composition of
      gut microbiota in infants with and without allergic diseases, particularly
      eczema. METHODS: A case-control study involving 21 toddlers (age 3.0 +/- 0.5
      years) with and 28 age-matched toddlers without eczema was conducted. Four groups
      of aerobic gut microbiota were identified and quantitated in stool samples grown
      on selective media. Three groups of anaerobes were enumerated by fluorescent in
      situ hybridization followed by quantitative flow cytometry. We also performed
      molecular typing of lactic-acid-producing bacteria (LAB) and enterococcal
      isolates to facilitate detailed analysis at species level by bacterial 16S rDNA
      sequencing. RESULTS: Toddlers with eczema harbored significantly lower counts of
      Bifidobacterium [(median 0.14 (25th and 75th percentile: 0.04 and 0.47) vs. 0.71%
      (0.16, 1.79) of cells acquired, p = 0.003)] and Clostridium [(0.28 (0.09, 0.78)
      vs. 0.83% (0.35, 1.82) of cells acquired, p = 0.012)] but significantly higher
      counts of total LAB [7.3 (6.1, 8.5) vs. 5.7 (4.4, 7.3) log CFU/g, p = 0.006] in
      particular enterococci [6.3 (4.8, 7.4) vs. 5.0 (3.4, 6.4) log CFU/g, p = 0.018].
      There was no significant correlation between eczema severity score and
      bifidobacterial counts. CONCLUSION: The results further confirm previous reports
      that the gut microecosystem differs between children with and without eczema and
      extend them beyond infancy.

PMID- 16601354
TI  - Tryptase as severity marker in drug provocation tests.
AB  - BACKGROUND: In the absence of objective symptoms, it is difficult to assess an
      adverse reaction during drug provocation testing. We evaluated the value of serum
      tryptase levels to distinguish between positive, negative and, even more
      important, so-called 'hysterical' reactions (conversion symptoms). The latter are
      occasionally observed in drug provocation tests when the patient experiences
      ambiguous subjective symptoms. METHODS: In a prospective single-center study, 303
      patients underwent 785 drug provocation tests. Blood was taken for tryptase
      measurement on each test day before and after drug challenge, and the changes in
      serum tryptase levels in patients with no reactions were compared with those who
      experienced immediate reactions to a drug. RESULTS: Thirty-four of 785 drug
      provocations were clinically judged as being positive. Despite objective
      symptoms, median serum tryptase values in the afternoon were even lower than
      baseline levels. However, this decrease was not statistically significant. In the
      751 patients suffering no objective reactions, the median values of post-testing
      tryptase values were statistically significantly decreased as compared with
      pretesting values. CONCLUSIONS: The measurement of serum tryptase levels does not
      appear to be helpful to differentiate mild allergic or nonallergic reactions from
      'hysterical' ones. The milder decrease in the group with objective drug reactions
      might indicate slight mast cell activation in some patients. More severe clinical
      drug reactions led to stronger mast cell degranulation. Mild reactions did not
      increase the tryptase levels consistently.

PMID- 16601355
TI  - Cross-sensitization between poppy seed and buckwheat in a food-allergic patient
      with poppy seed anaphylaxis.
AB  - The opium poppy, Papaver somniferum L., is the source of both poppy seeds and
      opium. The commercially available seeds are widely used as ingredients for
      various kinds of food. IgE-mediated sensitization to poppy seeds is rare, but, if
      present, clinical symptoms are usually severe. Cross-sensitizations between poppy
      seeds and other food allergens have been described with sesame, hazelnut, rye
      grain and kiwi fruit. We report the case of a 17-year-old female with an
      apparently food-allergic reaction after ingestion of a poppy seed cake.
      Allergological workup revealed a poppy seed anaphylaxis and led to the
      identification of a novel cross-sensitization with buckwheat.

PMID- 16601356
TI  - Type I regulatory T cells in autoimmunity and inflammatory diseases.
AB  - Regulatory T cells exert a critical role in controlling autoimmunity and
      maintaining peripheral tolerance. The best described regulatory T cells are the
      naturally occurring CD4+CD25+ regulatory T cells, which have been shown to be
      continuously produced within the thymus. Other T-cell subsets bearing suppressive
      capacity have been reported, including T-helper-3 cells (Th3) and type 1
      regulatory T (Tr1) cells. Tr1 cells have been shown to be induced upon antigen
      exposure under certain tolerogenic conditions and are characterized by the
      production of the immunosuppressive cytokines IL-10 and TGF-beta, while Th3 cells
      preferentially produce TGF-beta upon induction by intestinal tolerance. Recent
      progress has been made in the characterization of Tr1 cells in terms of isolation
      and induction, respectively. The present review provides an overview of the
      presence of Tr1 cells in inflammation, infection and neoplastic disorders.
      Moreover, the relationship between different regulatory T cell subsets and their
      transcriptional control is discussed. The recent development of methods allowing
      the ex vivo expansion of regulatory T cells may be the first step towards a
      cellular therapy with regulatory T cells to control T-cell-mediated pathology in
      inflammatory disorders.

PMID- 16601357
TI  - Co-expression of interleukin-2 by a bicistronic plasmid increases the efficacy of
      DNA immunization to prevent influenza virus infections.
AB  - A promising approach to protect susceptible individuals against severe diseases
      is the inoculation of plasmids. Such DNA vaccines against influenza virus
      infections were quite efficient in different animal models; but still this
      procedure is not in clinical use until today. The present study reports the
      generation and characterization of bicistronic plasmids which enables the
      expression of influenza A virus gene sequences together with immunostimulatory
      cytokines demonstrating that among these cytokines especially interleukin-2 (IL
      2) was efficient to prevent a lethal influenza virus infection in mice.

PMID- 16601358
TI  - Differential nephron HO-1 expression following glomerular epithelial cell injury.
AB  - BACKGROUND: In proteinuria of glomerular origin there is upregulation of heme
      oxygenase (HO), the rate-limiting enzyme of heme degradation, in the nephron in a
      segment-specific manner. To better characterize this phenomenon, we employed a
      model of proteinuria resulting from disruption of the glomerular capillary
      permeability barrier to protein by administration of the glomerular epithelial
      cell toxin puromycin aminonucleoside (PAN) to rats. In this model, we assessed
      nephron distribution of the expression of the inducible HO isoform, HO-1, and the
      role of free radicals in modulating HO-1 expression. METHODS: Rats were injected
      with either vehicle (dimethyl sulfoxide) or PAN or the spin trap free radical
      stabilizer alpha-phenyl-N-tert butyl nitrone (PBN), or with both PAN and PBN. Ten
      days following the PAN injection, urine protein, creatinine, nitric oxide (NO)
      and malonyldialdehyde (MDA) were measured. Kidney sections and protein lysates
      were assessed for changes in HO-1 expression by immunohistochemistry and Western
      blot analysis. RESULTS: In control animals (DMSO or PBN alone) there was no
      proteinuria and very weak or absent HO-1 staining in nephron segments. PAN
      treatment induced proteinuria and increased urine MDA excretion. In these
      animals, there was a robust HO-1 expression mainly in tubules and in glomerular
      parietal but not visceral epithelial cells. Unilateral ureteral obstruction to
      interrupt glomerular filtration in animals treated with PAN abrogated tubular HO
      1 expression in the kidney ipsilateral to the obstruction. Administration of PBN
      to PAN-treated animals reduced proteinuria and MDA excretion while it markedly
      augmented tubular HO-1 expression. This augmentation was prominent in tubular
      cells of the inner cortex/outer medulla. CONCLUSIONS: These observations indicate
      that upregulation of nephron HO-1 following disruption of the glomerular
      permeability barrier occurs at sites downstream of this barrier and is mediated
      by a filtered HO-1 inducer(s). Scavenging of free radicals potentiates the effect
      of this inducer and unmasks nephron segments most and least capable of
      upregulating HO-1.

PMID- 16601359
TI  - Effects of combined long-term treatment with a growth hormone-releasing hormone
      analogue and a growth hormone secretagogue in the growth hormone-releasing
      hormone knock out mouse.
AB  - GH secretagogues (GHS) are synthetic ghrelin receptor agonists that stimulate GH
      secretion. It is not clear whether they act predominantly by stimulating the
      secretion of hypothalamic growth hormone-releasing hormone (GHRH), or directly on
      the somatotrope cells. In addition, it is not known whether combined treatment
      with GHRH and GHS has synergistic effects on growth. To address these questions,
      we used the GH-deficient GHRH knock out (GHRHKO) mouse model, which has severe
      somatotrope cell hypoplasia. We treated GHRHKO mice for 5 weeks (from week 1 to
      week 6 of age) with the GHRH analogue JI-38 alone, or in combination with a GHS
      (GHRP-2), and at the end of the treatment we examined their response to an acute
      stimulus with GHRP-2 or GHRP-2 plus JI-38. We used placebo-treated GHRHKO mice
      and animals heterozygous for the GHRHKO allele as controls. Animals treated with
      JI-38+GHRP-2 reached higher body length and weight than animals treated with JI
      38 alone. All the animals receiving JI-38 (with or without GHRP-2) showed similar
      correction of somatotrope cell hypoplasia. None of the GHRHKO animals showed a
      serum GH response to the acute stimulation with GHRP-2 alone, while both treated
      groups responded to the combined test with JI-38 + GHRP-2. These data demonstrate
      that in GHRHKO mice, GHRP-2 has a growth-stimulating effect that augments the
      response induced by JI-38. In addition, the presence of GHRH seems necessary for
      the stimulation of GH secretion by GHRP-2.

PMID- 16601360
TI  - Metallothionein isoform 3 gene is differentially expressed in corticotropin
      producing pituitary adenomas.
AB  - In order to search for candidate genes related to pituitary adenoma
      aggressiveness, the present investigation was intended to compare the mRNA
      expression profile from a pool of four nonfunctional pituitary adenomas (NFPA)
      with a spinal cord metastasis of a nonfunctional pituitary carcinoma (MNFPC). The
      metallothionein isoform 3 (MT3) gene was differentially expressed in
      nonfunctional adenomas in comparison to the metastasis of nonfunctional
      carcinoma. A microarray dataset comprising 19,881 probes was employed for
      comparing expression profiles of a spinal cord metastasis of a nonfunctional
      pituitary carcinoma with a pool of four nonfunctional pituitary adenomas. RT-qPCR
      confirmed the microarray findings and was used to investigate MT3 mRNA gene
      expression in tumor samples of a series of 52 different pituitary adenoma
      subtypes comprising 10 corticotropin (ACTH)-producing, 18 growth hormone (GH)
      producing, 8 prolactin (PRL)-producing, and 16 nonfunctional adenomas. Microarray
      data analysis by GeneSifter program unveiled Gene Ontology terms related to zinc
      ion-binding activity closely related to MT3 function. MT3 mRNA expression was
      statistically significantly higher in ACTH-producing pituitary adenomas and in
      nonfunctional pituitary adenomas in comparison to the other pituitary adenoma
      subtypes. The more abundant expression of this gene in ACTH-producing pituitary
      adenomas suggests that MT3 could be related to distinct pituitary cell lineage
      regulating the activity of some transcription factor of importance in hormone
      production and/or secretion.

PMID- 16601361
TI  - Intertumoural variability in functional imaging within patients suffering from
      neuroendocrine tumours. An observational, cross-sectional study.
AB  - (123)I mIBG (meta-iodobenzylguanidine) and (111)In pentetreotide scintigraphy
      imaging modalities are useful in demonstrating neuroendocrine tumours. Although
      (111)In pentetreotide is generally held to be a more superior imaging agent than
      (123)I mIBG for neuroendocrine tumours, we noted a differential uptake of the two
      agents by different tumour sites within individual patients. In some cases, the
      two tracers appeared to demonstrate different lesions within the same patient.
      The aim of this study wasto determine the positivity of the two imaging
      modalities, the degree of correlation between them and to highlight any
      clinically useful differences between the two modalities. (123)I mIBG and (111)In
      pentetreotide images of 149 consecutive, biopsy-proven or biochemically
      confirmed, neuroendocrine tumour patients were compared. All the patients
      underwent whole-body imaging and upper abdominal single-photon emission computed
      tomography (SPECT). The results of both types of imaging were compared, lesion by
      lesion, for each individual patient. The overall positivity rate for (111)In
      pentetreotide was 79%, and that for (123)I mIBG was 63%. When both agents were
      positive, the (111)In pentetreotide highlighted more lesions within the same
      patient in 33%, whilst the (123)I mIBG highlighted more lesions in 13%. In 12% of
      patients both agents were positive, but different lesions were seen with the two
      agents. (111)In pentetreotide has greater positivity than (123)I mIBG for imaging
      neuroendocrine tumours. However, the two modalities can highlight different
      tumour lesions, suggesting the presence of phenotypically diverse tumour
      populations within individual patients. These findings are likely to influence
      clinical management in the future.

PMID- 16601363
TI  - Increased plasma nitric oxide metabolites in suicide attempters.
AB  - OBJECTIVE: To evaluate any correlation between plasma levels of nitric oxide
      metabolites (NO(x)) and suicide attempt. METHOD: Plasma NO(x) levels were
      measured in 53 patients who had recently attempted suicide, 58 non-suicidal
      psychiatric patients, and 75 normal controls. The severity of suicidal behaviors
      was evaluated using Weisman and Worden's Risk-Rescue Rating Scale. RESULTS:
      Plasma NO(x) levels were significantly higher in suicidal patients than non
      suicidal psychiatric patients or normal control subjects (F=11.029, d.f.=2, 183,
      p<0.001). Among the patients with a diagnosis of major depression, suicidal
      depressive patients had significantly higher plasma NO(x) levels than non
      suicidal depressive patients (t=-3.090, d.f.=84, p=0.003). CONCLUSION: Our study
      suggests that increased NO production in plasma is associated with suicide
      attempt, especially in depressive patients.

PMID- 16601362
TI  - Neural effects of nicotine during auditory selective attention in smokers: an
      event-related potential study.
AB  - Acute nicotine has been found to improve task performance in smokers after
      smoking abstinence, but the attentional processes mediating these improvements
      are unclear. Since scalp-recorded event-related potentials (ERPs) have been shown
      to be sensitive indicators of selective attention, the effects of acutely
      administered nicotine were examined on ERPs and concomitant behavioural
      performance measures in an auditory selective attention task. Ten (6 males)
      overnight smoking-abstinent cigarette smokers received nicotine gum (4 mg) in a
      randomized, double-blind, placebo-controlled, crossover design. In a dichotic
      listening task [which required participants to attend and detect (target) deviant
      stimuli in one ear and to ignore similar stimuli in the other ear] which included
      ERP recordings and assessment of response speed and accuracy measures, nicotine
      gum failed to alter behavioural performance or amplitudes of ERP components
      sensitive to selective attention [reflected in the N100 and negative difference
      (Nd) component] or to pre-attentive detection of acoustic change [reflected in
      the mismatch negativity (MMN) component]. However, nicotine did influence the
      speed of these voluntary selective processes, as reflected by shortened latencies
      of the early Nd component. The findings are discussed in relation to the stimulus
      filter theory of smoking, and with respect to nicotine's actions on involuntary
      and controlled aspects of selective attention processes.

PMID- 16601364
TI  - Prolactin serum levels and alcohol craving - an analysis using Lesch's typology.
AB  - BACKGROUND: Prolactin secretion is closely connected to dopaminergic transmission
      that is known to play a crucial role in mediating reinforcement and craving in
      alcoholism. OBJECTIVES: The study was performed to analyze the association
      between prolactin serum levels and alcohol craving during withdrawal
      differentiating alcohol-dependent patients using Lesch's typology. METHODS: We
      assessed 115 male patients with the Obsessive Compulsive Drinking Scale at early
      alcohol withdrawal. In addition, serum was obtained to measure prolactin
      concentration and the patients were classified according to Lesch's typology into
      one of four subgroups. RESULTS: Correlation analysis showed a significant
      association between prolactin serum levels and the extent of craving in Lesch's
      type 2 patients (r=0.32, p=0.015; n=57); however, no association was found for
      any other subgroup. The results were confirmed comparing patients with low and
      high craving (Mann-Whitney U test: Z=-2.805, p=0.005). CONCLUSIONS: In patients
      of Lesch's type 2, who are characterized to suffer from anxiety and to use
      alcohol because of its anxiolytic effects, prolactin is associated with craving
      during early alcohol withdrawal.

PMID- 16601365
TI  - Should men with serum prostate-specific antigen < or =4 ng/ml and normal digital
      rectal examination undergo a prostate biopsy? A literature review.
AB  - The clinical significance of a prostate cancer (PCa) cannot be determined solely
      by tumor volume (< or =0.5 cm(3)), as small tumors of higher Gleason grade and
      tumors occurring in younger men may become clinically significant even though the
      initial volume at diagnosis is small. A certain number of these minimal cancers
      are likely to remain clinically insignificant; however, it is unpredictable how
      many can progress beyond the curable stage by the time there is a rise in serum
      prostate-specific antigen (PSA) values. Compared to clinically detected PCa, PCa
      detected exclusively by PSA screening (clinical stage T1c) are less likely to be
      advanced but no more likely to be insignificant in terms of volume, pathologic
      stage, and Gleason pattern. Only 10-15% of PSA-detected cancers have the features
      of PCa found at autopsy or in cystoprostatectomy specimens. Actually, 25-30% of
      PCa are detected with PSA values between 2.5 and 4 ng/ml, and most of these
      cancers are clinically significant. Evidence from both retrospective and
      longitudinal studies has shown that the risk of a PCa is dependent on the
      patient's age and the initial serum PSA. This allows an individualized approach
      to PCa screening programs, and PSA cutoff values for biopsy indication may be
      lowered in selected patients.

PMID- 16601366
TI  - CBHA is a family of hybrid polar compounds that inhibit histone deacetylase, and
      induces growth inhibition, cell cycle arrest and apoptosis in human endometrial
      and ovarian cancer cells.
AB  - OBJECTIVES: We investigated the effect of a novel synthesized histone deacetylase
      inhibitor (HDACI), CBHA, on three endometrial cancer cell lines, two ovarian
      cancer cell lines, and normal human endometrial epithelial cells. METHODS:
      Endometrial and ovarian cancer cells were treated with various concentrations of
      CBHA, and its effect on cell growth, cell cycle, apoptosis, and related
      measurements was investigated. RESULTS: The 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay showed that all endometrial and ovarian cancer
      cell lines were sensitive to the growth-inhibitory effect of CBHA, although
      normal endometrial epithelial cells were viable after treatment with the same
      doses of CBHA that induced growth inhibition in endometrial and ovarian cancer
      cells. Cell cycle analysis indicated that their exposure to CBHA decreased the
      proportion of cells in the S-phase and increased the proportion in the G(0)/G(1)
      phases of the cell cycle. Induction of apoptosis was confirmed by annexin V
      staining of externalized phosphatidylserine and loss of the transmembrane
      potential of mitochondria. This induction occurred in concert with altered
      expression of genes related to cell growth, malignant phenotype, and apoptosis.
      Furthermore, CBHA treatment of these cell lines increased acetylation of H3 and
      H4 histone tails. CONCLUSIONS: These results raise the possibility that CBHA may
      prove particularly effective in the treatment of endometrial and ovarian cancers.

PMID- 16601367
TI  - The prognostic determinants of gastric cancer treatment outcome in Omani Arab
      patients.
AB  - BACKGROUND: Gastric cancer is the most common cancer in Oman and a leading cause
      of cancer death. The variation in survival rates between countries and ethnic
      groups has been attributed to early detection policies, differences in
      clinicopathological features, treatment approaches, and biological
      characteristics. There were no previous reports on gastric cancer from Oman and
      very few studies on Asian Arabs. AIM: To evaluate the impact of
      clinicopathological and treatment variables on the survival prospects of Omani
      Arab patients diagnosed with gastric cancer. METHODS: The medical records of 339
      Omani Arab patients diagnosed with invasive gastric adenocarcinoma during the
      period 1993-2004 were retrospectively reviewed. The relative importance of
      clinicopathological features and surgical and medical treatments were assessed
      using univariate and multivariate analyses. RESULTS: Most patients had distal
      ulcerating-type gastric cancer and presented at advanced stages. The median
      survival time for the entire cohort was 12 months (95% CI 9.7-14.4) with a 5-year
      overall survival rate of 16.7%. On univariate analysis of 237 patients who
      underwent surgical resection, the following positive prognostic factors emerged
      as significant: early overall TNM stage, early T stage, negative lymph nodes,
      tumor size <5 cm, ulcerating macroscopic appearance, and curative surgical
      attempt. The independent prognostic factors on multivariate analysis were T stage
      and lymph node involvement. CONCLUSION: The overall T and N stages are the most
      important determining factor for survival in Omani Arab patients. More efforts
      need to be made for the early detection of gastric cancer in developing countries
      such as Oman, while continuing to employ the standard surgical and medical
      treatments.

PMID- 16601368
TI  - Spontaneous remission of cancer - enigma and paradigm.

PMID- 16601369
TI  - Oral vinorelbine and cisplatin with concomitant radiotherapy in stage III non
      small cell lung cancer (NSCLC): a feasibility study.
AB  - BACKGROUND: Concurrent chemoradiotherapy has improved survival in inoperable
      stage III non-small cell lung cancer (NSCLC). This phase I trial was performed in
      order to establish a dose recommendation for oral vinorelbine in combination with
      cisplatin and simultaneous radiotherapy. PATIENTS AND METHODS: Previously
      untreated patients with stage IIIB NSCLC received concurrent chemoradiotherapy
      with 66 Gy and 2 cycles of cisplatin and oral vinorelbine which was administered
      at 3 different levels (40, 50 and 60 mg/m2). This was to be followed by 2 cycles
      of cisplatin/ vinorelbine oral consolidation chemotherapy. The study goal was to
      determine the maximal recommended dose of oral vinorelbine during concurrent
      treatment. RESULTS: 11 stage IIIB patients were entered into the study. The
      median radiotherapy dose was 66 Gy. Grade 3-4 toxicity included neutropenia,
      esophagitis, gastritis and febrile neutropenia. The dose-limiting toxicity for
      concurrent chemoradiotherapy was esophagitis. 9 patients received consolidation
      chemotherapy, with neutropenia and anemia/thrombocytopenia grade 3 being the only
      toxicities. The overall response was 73%. CONCLUSION: Oral vinorelbine 50 mg/m2
      (days 1, 8, 15 over 4 weeks) in combination with cisplatin 20 mg/m2 (days 1-4) is
      the recommended dose in combination with radiotherapy (66 Gy) and will be used
      for concurrent chemoradiotherapy in a forthcoming phase III trial testing the
      efficacy of consolidation chemotherapy in patients not progressing after
      chemoradiotherapy.

PMID- 16601370
TI  - Diagnostic value of 123I-IMT SPECT in the follow-up of head and neck cancer.
AB  - BACKGROUND: Nuclear medicine imaging is increasingly used in the evaluation of
      tumors of the head and neck. In the current study, we assess the value of single
      photon emission tomography (SPECT) using the amino acid tracer L-3-[123I]iodine
      alpha-methyl-tyrosine (IMT) for the detection of recurrent head and neck cancer.
      PATIENTS AND METHODS: 45 consecutive patients with suspected recurrence of
      previously treated head and neck cancer were examined by IMT-SPECT using a dual
      head system with integrated low-dose computed tomography (CT). The accuracy of
      the IMT-SPECT was evaluated by correlating the findings with results of histology
      or clinical and CT/MRI (magnetic resonance imaging) follow-up examinations.
      RESULTS: The sensitivity, specificity and accuracy of IMT-SPECT in the detection
      of recurrent/persistent tumors were 83, 89 and 84.5%, respectively. The positive
      and negative predictive value amounted to 96.5 and 60%, respectively. CONCLUSION:
      IMT-SPECT using integrated low-dose CT appears to be a helpful complementary
      imaging tool for the detection of local recurrences and lymph node metastases of
      head and neck cancer and their differentiation from treatment-induced changes.
      The advantage of the method is the high positive predictive value in the
      diagnosis of relapsed tumors. However, a negative IMT-SPECT result does not
      exclude a recurrence.

PMID- 16601372
TI  - Spontaneous remission of metastases of cancer of the uterine cervix.
AB  - BACKGROUND: Spontaneous remission (SR) is the complete or incomplete
      disappearance of a disease or cancer despite no or inadequate treatment. SR is a
      rare event, and only 5 cases of SR of carcinoma of the uterine cervix have been
      reported so far. CASE REPORT: We report the case of a young woman suffering from
      carcinoma of the uterine cervix metastasized to the lung, pleura, bone, skin and
      brain. The primary tumor was removed. After diagnosis of the histologically
      proven metastases, further palliative treatment was inadequate, except for
      radiotherapy to the brain. In all other metastases, spontaneous remission
      occurred. 8 years after the initial diagnosis of metastasis, there is no evidence
      of active disease. CONCLUSION: SR is a rare but evident phenomenon. Individual
      features of malignant tumors should be taken into account much more when
      determining the best treatment for the patient.

PMID- 16601371
TI  - Minimal change glomerulonephritis in chronic lymphocytic leukemia:
      pathophysiological and therapeutic aspects.
AB  - BACKGROUND: So far, only 9 cases of minimal change glomerulonephritis (MCGN)
      related to chronic lymphocytic leukemia (CLL) have been described. CASE REPORT:
      Our patient presented with severe nephrotic syndrome. Diagnostic biopsies
      confirmed MCGN and early-stage BCLL (Binet A). In contrast to previously
      described cases, kappa monoclonal IgM and cryoglobulins were also detected. The
      patient was treated with chlorambucil and prednisone. 3 weeks later, renal
      function and white blood cell (WBC) count were completely normal. DISCUSSION:
      Although, in most cases, renal disease and CLL present separately, there is
      evidence for a causal relationship between the two disorders. Although it is
      widely approved that early-stage CLL should not be treated by medication, the
      severe nephrotic syndrome in our patient required immediate intervention. So far,
      there is no standard therapy for MCGN associated with CLL. Our combination
      therapy resulted in normalization of the nephrotic syndrome and the WBC count.
      Hence, we emphasize the importance of early recognition of renal symptoms in CLL
      and propose a successful therapy for nephrotic syndrome in MCGN associated with
      early-stage B-CLL. Additionally, the pathophysiological and therapeutic aspects
      of MCGN associated with CLL are retrospectively discussed.

PMID- 16601373
TI  - Proteasome inhibition: novel therapy for multiple myeloma.
AB  - Therapeutic options for patients with myeloma are a rapidly advancing area of
      research due in part to an increase in the understanding of myeloma biology as
      well as the development of novels agents. Proteasome inhibition is a novel
      modality for the treatment of patients with myeloma. Bortezomib, a novel
      proteasome inhibitor, was effective in a broad range of tumor cell lines in
      preclinical testing. In phase I trials, bortezomib was noted to be active in
      patients with multiple myeloma and lymphoma. This led to several multicenter
      trials confirming the safety and efficacy of bortezomib for patients with
      relapsed and refractory myeloma. Most recently, a large randomized phase III
      trial comparing bortezomib with high-dose dexamethasone demonstrated that
      bortezomib had an improved response rate, duration of remission and overall
      survival advantage in the setting of relapsed disease. These findings have led
      investigators to study proteasome inhibition with conventional chemotherapy and
      other novel agents. In addition, several recently completed and ongoing studies
      are evaluating the role of bortezomib in the initial treatment of myeloma. The
      success of proteasome inhibition in the treatment of myeloma is a model for
      effective translation of preclinical research into tangible clinical benefits for
      patients with cancer.

PMID- 16601374
TI  - G-CSF in the prevention of febrile neutropenia in chemotherapy in breast cancer
      patients.
AB  - The most common chemotherapeutic agents in the treatment of breast cancer are
      anthracyclines and taxanes. The major dose-limiting toxicities associated with
      these agents are myelosuppression and associated febrile neutropenia (FN). FN can
      significantly impact the ability to deliver full-dose chemotherapy on schedule
      and as a result may increase the risk of disease recurrence and eventual disease
      related mortality. The use of granulocyte colony stimulating factors (G-CSFs)
      significantly improves the management of FN, both in a therapeutic and in a
      prophylactic approach. Nevertheless, the high cost of these agents limits their
      widespread prophylactic use. Therefore, the identification of patients who are at
      a higher risk of developing FN and who will benefit from the prophylactic use of
      G-CSFs has become the subject of several clinical and cost-effectiveness studies.
      Recently, new data have been accumulated concerning the risk of FN in different
      chemotherapy regimens, and different risk models have been developed to assess
      the neutropenic risk with all its complications. This article reviews and
      summarizes cutting-edge, disease-specific data as well as national and
      international guidelines regarding the use of G-CSFs to prevent chemotherapy
      induced FN, with focus on the treatment of breast cancer.

PMID- 16601375
TI  - Rapid resolution of liver metastasis from cholangiocarcinoma after bevacizumab
      with cisplatin and high-dose fluorouracil plus leucovorin.

PMID- 16601376
TI  - Hypofractionated stereotactic radiation therapy for skull base and upper cervical
      chordoma and chondrosarcoma: preliminary results.
AB  - INTRODUCTION: Chordoma and chondrosarcoma are rare tumors of the base of the
      skull and are difficult candidates for surgical treatment. They are also usually
      resistant to conventional radiation therapy. We report preliminary results of
      hypofractionated stereotactic radiation therapy (SRT) using the Cyberknife system
      (Accuray Inc., Sunnyvale, Calif., USA) for primary and recurrent chordomas and
      chondrosarcomas of the skull base and upper cervical region. MATERIAL AND
      METHODS: Nine pathologically proven chordoma/chondrosarcoma patients underwent
      Cyberknife treatment, and in 4 patients Cyberknife was performed as a primary
      adjuvant treatment after operation. Remainder of the patients had previously
      received conventional radiotherapy except 1 who had received Gamma Knife
      treatment. The prescribed tumor dose ranged from 21 to 43.6 Gy in three to five
      fractions. The dosimetric characteristics were evaluated for conformity and
      coverage indices. Dose volume histograms of both the tumor and the critical
      structure were obtained, and the dose delivered to a specific volume (25, 50 and
      100%) of the critical structure was calculated in each case. Mass response was
      measured on follow-up MRI scans. Total tumor doses of different fractionation
      numbers were converted into single session equivalent doses and linear quadratic
      equivalent doses of conventional radiation for comparison among patient groups.
      RESULT: No significant complications were observed during the treatment and early
      follow-up periods except one instance of transient esophagitis and one instance
      of otitis. All treatment plans met the criteria for standard protocol of
      radiosurgery suggested by the Radiation Therapy Oncology Group, specifically in
      terms of conformity index, which ranged from 1.01 to 1.83. Three plans had a
      coverage index that was rated as a minor acceptable deviation. All patients were
      followed from 11 to 30 (median 24) months following the treatment with regular
      magnetic resonance images, and 4 patients showed mass reduction. Disease
      progression was not noted in any patient during the above follow-up period except
      1 patient who showed asymptomatic recurrence on 27-month follow-up MRI. Dose
      volume histograms revealed that the relative dose to volume percent of critical
      structure, measured at 25, 50 and 100%, was apparently lower in the pretreatment
      surgical decompression group than in the nondecompression group. Two patients
      developed radiation-induced myelopathy. The delivered radiation dose to the
      critical structure calculated using the linear-quadratic formula was within the
      acceptable range in one case and exceeded 70 Gy at 50% volume of the spinal cord
      in the other. CONCLUSION: The hypofractionated Cyberknife SRT is effective in
      generating therapeutic response in these radioresistant tumors, with minimal
      toxicity during the procedure and early follow-up period. Repeated radiosurgical
      treatment may also be feasible for tumor recurrences but deserves great caution
      with respect to the biological effects of the accumulated dose on the adjacent
      critical structures. Cyberknife SRT may be a potentially valuable treatment
      option once the long-term results and appropriate dose calculators are optimally
      defined.

PMID- 16601377
TI  - Rehabilitation therapy and urinary incontinence after radical retropubic
      prostatectomy. A critical review of the literature.
AB  - INTRODUCTION: To assess the efficacy and evidence-based data in the literature
      about rehabilitation therapy in patients with post-prostatectomy urinary
      incontinence. MATERIALS AND METHODS: An analysis of published full-length papers
      identified by a Medline search from 1990 through 2004 was carried out. Abstracts
      published in peer-reviewed journals in the same period of time were also
      considered. RESULTS: Efficacy, tolerability and safety of rehabilitation therapy
      were evaluated, according to the available data in the literature, with special
      regard to randomized controlled trials in order to define a clear-cut, evidence
      based efficacy of this form of therapy. CONCLUSIONS: Rehabilitation therapy is a
      simple and safe way of managing post-prostatectomy urinary incontinence.
      Nonetheless, few randomized controlled studies have been carried out so far to
      establish its evidence-based efficacy and it is thus not possible to be
      scientifically sure of its value. It is therefore necessary to undertake well
      designed randomized controlled studies, with a large number of patients, a well
      matched control group and an adequate follow-up.

PMID- 16601378
TI  - Introducing a novel technique to remove accidentally stitched or entrapped
      urethral catheters after radical prostatectomy.
AB  - INTRODUCTION: A crucial step during radical prostatectomy is anastomosing the
      bladder neck to the urethral stump after specimen removal. For this purpose, a
      Foley catheter is inserted transurethrally to achieve a patent and watertight
      anastomosis. The catheter should be removed 6-10 days after the procedure to
      avoid ascending infection and stricture formation. On occasion, catheter removal
      is not possible due to fixation by one of the anastomotic sutures. In this case,
      a longer catheterization period may increase the risk of infection and formation
      of an anastomotic stricture. MATERIALS AND METHODS: In the present report, we
      suggest a technique to overcome this problem by using an endoscopic laser
      dissection of the anastomotic suture. In 2 patients, a 4.8-Fr pediatric
      ureteroscope was passed through the urethra along the fixated catheter. After
      carefully inspecting the anastomosis, a laser fiber was brought in direct contact
      with the responsible suture. RESULTS AND CONCLUSIONS: By activating the laser,
      the suture was cut immediately, and the catheter could be removed. Both patients
      showed no signs of anastomotic leakage or stricture on cystography. Fixation of
      the catheter after radical prostatectomy is a rare, but bothersome complication,
      which can compromise the functional outcome of the procedure. Using a pediatric
      ureteroscope and a laser fiber is an elegant, minimally invasive method to solve
      this problem. It can be easily and safely performed under local anesthesia in an
      outpatient setting.

PMID- 16601379
TI  - Clinical and pathological characteristics of patients presenting with biochemical
      progression after radical retropubic prostatectomy for pathologically organ
      confined prostate cancer.
AB  - INTRODUCTION: To identify risk factors for biochemical failure after radical
      prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer
      (PCa). MATERIALS AND METHODS: Clinical and pathological features of 350
      consecutive patients with pathologically OC PCa treated only with RP and
      bilateral pelvic lymphadenectomy were analyzed, retrospectively, to identify
      predictor parameters of prostate-specific antigen (PSA) failure (PSA>or=0.4
      ng/ml). The median follow-up was 58.6 months (range: 3.9-183 months). All
      pathological specimens were step sectioned at 4-mm intervals. Kaplan-Meier
      progression-free survival rates and chi2 test were adopted for statistical
      analyses. Multivariate Cox proportional hazard regression models were used to
      test the association between pathological Gleason score and surgical margin
      status. RESULTS: 67 patients (19.1%) failed at a median follow-up of 40.2 months
      (range 1.9-123.3). Age and preoperative PSA failed to reveal significance also in
      patients with serum PSA>or=20 ng/ml (p=0.46). Patients with T3 clinical stage had
      a higher progression rate compared to T1C and T2 (43.5 vs. 27.8 and 17.3%,
      respectively) even if no high statistical significance was pointed out. Presence
      of perineural infiltration (p=0.04) and prostatic apex infiltration (p=0.74) in
      the prostatectomy specimens failed to reveal significance. A high pathological
      Gleason score (>or=7; p=0.0003) and surgical margin status (p<0.0001) were shown
      to be the most powerful predictive parameters of biochemical progression.
      CONCLUSIONS: In patients with pathologically OC PCa the presence of a high
      pathological Gleason score and positive surgical margins appear to represent the
      most important factors for prediction of outcome following RP.

PMID- 16601381
TI  - Erectile function after non-nerve-sparing radical prostatectomy: fact or fiction?
AB  - OBJECTIVE: To evaluate the potency in patients after radical perineal
      prostatectomy with wide excision of both neurovascular bundles. MATERIAL AND
      METHODS: In this prospective study, a quality-of-life questionnaire was completed
      by 128 patients at the preoperative stage, and 6 and 12 months postoperatively.
      Ten questions concerning the patient's sexuality were included on the pre- and
      both postoperative questionnaires. In addition, 6 patients who recorded some
      erectile function were sent a separate questionnaire containing eight more
      detailed questions. RESULTS: Preoperatively, 74/128 (57.8%) patients reported
      erections sufficient for sexual intercourse, and of these 74, 6 (8.1%) described
      having spontaneous erections 1 year postoperatively. These spontaneous erections
      occurred 1-5 times per week. The reply to the separate mailing made clear that
      the reported erections were insufficient for intercourse. CONCLUSIONS: Patients
      undergoing standardized radical prostatectomy with wide excision of the
      neurovascular bundle have a very small chance of spontaneous erections sufficient
      for intercourse postoperatively.

PMID- 16601380
TI  - A study on staging bone scans in newly diagnosed prostate cancer.
AB  - OBJECTIVE: This study aimed to evaluate the role of bone scan as a staging
      investigation in newly diagnosed untreated prostate cancers. MATERIALS AND
      METHODS: Bone scan results in patients with newly diagnosed prostate cancer were
      reviewed and correlated with clinical stage, prostate-specific antigen (PSA) and
      Gleason scores from the biopsy specimen. RESULTS: In all, 124 patients fulfilled
      inclusion criteria with an age range of 51-94 (mean 72.3) years. Pre-biopsy PSA
      ranged from 2.2 to 5,864 with a median of 21.1 ng/ml. Clinical stage was T0-T1c
      14.5%, T2a 41.9%, T2b 17.7%, T3 16.9%, and T4 9%. A Gleason score of 7 was found
      in 31%. Four patients' samples were not suitable for Gleason scoring. Twenty
      patients (16.1%) had a positive bone scan with a mean age of 79.4 years (median
      83). Two patients with PSA<20 ng/ml were positive. Of the 44 scans performed in
      the patients with PSA<or=20 ng/ml, clinical stage<T4 and Gleason sum<or=7 (with
      the major Gleason<4), none was positive. The above criteria give a 100% negative
      predictive value for avoiding bone scans as a staging investigation. CONCLUSIONS:
      Staging bone scan can be safely omitted in patients with a clinical stage of <T4,
      PSA level of <or=20 ng/ml and a Gleason score of <or=7 (with major Gleason
      pattern<4) unless the symptoms are suggestive of metastasis.

PMID- 16601382
TI  - Predictive ability of partin tables 2001 in a Welsh population.
AB  - OBJECTIVES: Partin tables are widely used to select and counsel patients prior to
      radical surgery for prostate cancer. However, Partin tables have been developed
      in the USA which has a different ethnic mixture from that of North Wales. We
      aimed to assess Partin tables' predictive ability in a Welsh population.
      MATERIALS AND METHODS: 193 patients underwent radical retropubic prostatectomy
      for clinically localized carcinoma of the prostate between April 1993 and July
      2004 in a single institution in North Wales. Complete preoperative clinical
      staging information was available in 177 patients. Receiver operating
      characteristic curve analysis was used. RESULTS: The mean patient age was 64 (48
      73) years. Preoperative clinical staging distribution was: T1c 46.6% and T2
      53.4%. 75% had organ-confined disease (TNM 1992). Extracapsular extension without
      seminal vesicle or lymph node involvement was seen in 13.5%. Nine percent had
      seminal vesicle invasion without lymph node involvement. Lymph node metastasis
      was found in 2.2%. The predictive effectiveness of the Partin table was high with
      an area under ROC curve of 0.733 for organ confinement, 0.738 for seminal vesicle
      invasion and 0.780 for lymph node involvement (CI 95%). CONCLUSION: Our study
      demonstrated that the predictive ability of Partin tables for prostate cancer is
      also applicable to a Welsh population.

PMID- 16601383
TI  - Impact of comorbidities on post-prostatectomy incontinence.
AB  - INTRODUCTION: The aim of this retrospective study was to evaluate various factors
      that may influence post-prostatectomy incontinence (PPI). PATIENTS AND METHODS:
      1,088 men with prostate cancer underwent radical retropubic prostatectomy. 742
      patients were evaluable for analysis. Continence was defined as usage of no or
      one pad daily. Mean follow-up was 45 months (12-143). RESULTS: Based on
      protective pad requirement 100% and 76% of men were continent at baseline and at
      the time of questionnaire evaluation (at least 12 months), respectively.
      Univariate analysis was performed to identify factors that may influence the
      return of continence. Age, body mass index (BMI), previous TUR-P, smoking,
      hypertension, diabetes and attempted nerve sparing did not predict postoperative
      continence status. CONCLUSIONS: In contrast to several reports, our analysis
      revealed that age, BMI, previous TUR-P, smoking, hypertension and diabetes do not
      have a statistically significant impact on continence after radical retropubic
      prostatectomy and are therefore not useful as predictors for PPI.

PMID- 16601384
TI  - Usefulness of the nadir value of serum prostate-specific antigen measured by an
      ultrasensitive assay as a predictor of biochemical recurrence after radical
      prostatectomy for clinically localized prostate cancer.
AB  - INTRODUCTION: The objective of this study was to determine whether the nadir
      value of serum prostate-specific antigen (PSA) measured by an ultrasensitive
      assay could be a useful predictor of biochemical recurrence after radical
      prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS:
      This study included 127 patients who underwent radical prostatectomy for
      clinically localized prostate cancer without neoadjuvant hormonal therapy and
      were pathologically diagnosed as negative for lymph node metastasis. The serum
      PSA value was measured using an ultrasensitive PSA assay system (Roche
      Diagnostics, Mannheim, Germany), and the findings were analyzed with respect to
      several clinicopathological factors. In this series, biochemical recurrence was
      defined as PSA persistently >0.2 ng/ml. RESULTS: Based on the nadir PSA value, we
      divided 127 patients into three groups as follows: group A (n=99):<or=0.01 ng/ml;
      group B (n=16): 0.01-0.05 ng/ml, and group C (n=12): >or=0.05 ng/ml. The nadir
      PSA value was significantly associated with preoperative PSA value, but not other
      conventional clinicopathological prognostic parameters. During the observation
      period (median 31 months, range 6-75 months), biochemical recurrence occurred in
      16 patients, that is, 1 in group A (6.3%), 4 in group B (25.0%), and 11 in group
      C (91.7%). Multivariate analysis using the Cox proportional hazards regression
      model indicated that the nadir PSA value was an independent predictor for
      biochemical recurrence after radical prostatectomy. CONCLUSION: These findings
      suggest that the nadir serum PSA value measured by an ultrasensitive assay could
      be a useful predictor of biochemical recurrence after radical prostatectomy for
      clinically localized prostate cancer, and that careful follow-up should be
      considered in cases demonstrating a nadir PSA value>0.01 ng/ml because of the
      significantly higher probability of biochemical recurrence in such cases.

PMID- 16601385
TI  - Is free/total PSA predictive of pathological stage and Gleason score in patients
      with prostate cancer and serum PSA<or=10 ng/ml?
AB  - INTRODUCTION: To evaluate whether percent free prostate-specific antigen (%-fPSA)
      could be predictive of pathological stage and Gleason score in patients with
      prostate cancer (PCa) and serum PSA of 10 ng/ml or less. MATERIALS AND METHODS:
      In 100 patients with total PSA<or=10 ng/ml who underwent radical retropubic
      prostatectomy as primary treatment of PCa, %-fPSA levels in organ-confined vs.
      non-organ-confined PCa and in patients with Gleason score<or=or>7 were compared.
      RESULTS: 32 patients had an organ-confined and 68 a locally advanced PCa. Median
      %-fPSA level was 15%; Gleasonscore was <7 in 49 patients, equal to 7 in 40 and >7
      in 11. Median %-fPSA levels in PCa with Gleason score<or=or>7 was 14, 15.5 and
      15%, respectively. Multiple logistic regression analysis did not show any
      correlation between %-fPSA in organ-confined vs. non-organ-confined PCa
      (p=0.4991) either between Gleason score<7 vs. equal to 7 (p=0.588) or >7
      (p=0.547). CONCLUSIONS: %-fPSA cut-off does not seem to be useful for
      preoperative staging of patients with PCa and serum PSA<or=10 ng/ml.

PMID- 16601386
TI  - Hypoechoic space formation with periprostatic nerve block: myth or reality?
AB  - INTRODUCTION: The most efficacious and commonly applied anesthetic technique for
      prostate biopsy is periprostatic block. In a previous publication, the creation
      of a 'hypoechoic space' at the injection site was described. This was reported to
      be a routine and essential part of the technique in various subsequent series. We
      were interested in assessing the incidence of the formation of such a hypoechoic
      area, and more importantly, whether it had any impact on pain management.
      MATERIALS AND METHODS: One hundred and eleven consecutive patients were
      prospectively evaluated. Local anesthetic consisted of 2.5 ml of 2% lidocaine for
      each side of the prostate. Infiltration was done within the neurovascular space
      at the base of the prostate just lateral to the junction between the prostate and
      the seminal vesicle. The creation of a hypoechoic nodule was recorded in three
      categories: no formation, unilateral or bilateral formation. Three groups were
      compared regarding the intensity of pain using a numeric analog scale. RESULTS:
      No hypoechoic area was formed in 30 (27%) patients. A unilateral nodule was
      created in 40 (36%), and a bilateral nodule was seen in 41 (37%) patients. The
      median pain scores were 3.3, 2.5 and 1.3 for the no hypoechoic wheal, unilateral
      and bilateral wheal groups, respectively (p<0.0001). CONCLUSION: Our results
      suggest that the creation of a hypoechoic space with anesthetic infiltration for
      prostate biopsy is indeed an important aspect of the technique with regard to
      pain control; however, it may not be accomplished in every case.

PMID- 16601387
TI  - Can MRI predict which patients are most likely to benefit from percutaneous
      positioning of volume-adjustable balloon devices?
AB  - PURPOSE: To assess whether magnetic resonance imaging (MRI) is useful in
      predicting which patients affected by stress urinary incontinence (SUI) will
      benefit from a new anti-incontinence therapy named adjustable continence therapy
      (AC). METHODS: We prospectively evaluated a group of 25 female patients affected
      by SUI and treated with ACT. Before and after treatment all patients were
      clinically assessed by physical examination, urodynamic evaluation and pad test.
      All patients had an MR examination before and 3 and 12 months after ACT surgery
      to compare the position of the bladder neck in relation to the pubococcygeal line
      (PCL). RESULTS: 21/25 (84%) patients were improved; 16 (64%) of these patients
      were dry and 5 (20%) significantly improved. Before treatment, the mean PCL
      distance was significantly different (p<0.01) between the responsive and the non
      responsive groups. CONCLUSIONS: MRI provides an effective radiological method to
      predict the efficacy of the ACT.

PMID- 16601388
TI  - Distal hypospadias repair in adults: the results of 97 cases.
AB  - INTRODUCTION: We reviewed our 9-year experience on 97 men with distal hypospadias
      who had undergone hypospadias surgeries. SUBJECTS AND METHODS: Patients were
      divided into two groups: group 1 included 17 men who had one or more unsuccessful
      surgeries in their childhood, and group 2 included 80 men with no previous
      hypospadias repairs. Meatal positions were glanular in 6, coronal in 35 and
      subcoronal in 56 patients. Our 97 hypospadias surgeries involved 42 meatal
      advancement and glanuloplasty, 41 Mathieu and 14 tubularized incised plate
      urethroplasty procedures. RESULTS: The overall success rate was 88% (86 of the 97
      patients). The success rate was 76.5% for group 1 (13 of the 17 patients) and
      91.3% for group 2 (73 of the 80 patients). Better voiding function and good
      cosmetic appearance was achieved in all patients. Urinary flow rates were
      significantly higher in all groups postoperatively. The success rates were 91.4
      and 85% for the patients with preoperative coronal and subcoronal meatal
      positions, respectively. The success rate was significantly lower in crippled
      cases and in cases with longer neourethra. CONCLUSION: Although the same
      techniques are used for children and adults in hypospadias surgery, the results
      in adults differ from those in children. The success rate for primary adult cases
      is quite acceptable, but it is decreased in patients having longer neourethra and
      having multiple previous interventions.

PMID- 16601389
TI  - Retroperitoneoscopic radical nephrectomy in obese patients: outcomes and
      considerations.
AB  - OBJECTIVE: To determine whether obesity is associated with surgical outcome in
      Japanese patients undergoing retroperitoneoscopic radical nephrectomy (RRN).
      PATIENTS AND METHODS: Between November 1999 and March 2005, we performed 98 RRN
      procedures for patients with renal cell carcinoma. Patients with a body mass
      index (BMI) of 25.0 or more were defined as obese (group A, n=33) and those with
      a BMI of <25.0 were defined as non-obese (group B, n=65), in accordance with the
      criteria of the Japan Society for the Study of Obesity. Patient background,
      degree of surgical invasiveness, and period of convalescence were compared
      between groups A and B. RESULTS: No statistically significant differences were
      observed between the groups in terms of age, gender, tumor laterality, tumor
      size, and time until resumption of oral intake and ambulation. However group A
      had a significantly longer insufflation time (172.1 vs. 137.4 min), greater blood
      loss (195.3 vs. 48.4 ml) and higher renal specimen weight (440.0 vs. 306.0 g)
      than group B. CONCLUSION: Obesity is not a factor that affects patient
      eligibility for RRN, but is a risk factor for longer insufflation time and
      greater blood loss.

PMID- 16601390
TI  - Metastatectomy prior to immunochemotherapy for metastatic renal cell carcinoma.
AB  - INTRODUCTION: We reviewed our experiences in performing cytoreductive
      metastatectomy before initiating systemic immunochemotherapy and tried to
      investigate potential prognostic factors for such an approach. PATIENTS AND
      METHODS: A retrospective analysis of 57 patients who received interleukin-2,
      interferon-alpha, and 5-fluorouracil immunochemotherapy for metastatic renal cell
      carcinoma was conducted. Before undergoing immunochemotherapy, 20 of the 57
      patients had received metastatectomy along with nephrectomy (metastatectomy
      group) and the other 37 nephrectomy alone (non-metastatectomy group). RESULTS:
      The metastatectomy group demonstrated median disease-specific and progression
      free survival of 23 and 13 months, respectively. The patients in the
      metastatectomy group were identified as having a better performance status and
      primarily demonstrating pulmonary metastasis compared with those in the non
      metastatectomy group. As assessed in the metastatectomy group, factors such as
      the number of metastatic lesions, completeness of metastatectomy, and location of
      metastatic lesions (lung only vs. others) were observed to be significantly
      associated with overall survivals on univariate analysis. CONCLUSIONS:
      Metastatectomy may still play a significant therapeutic role for metastatic renal
      cell carcinoma even in the era of immunochemotherapy as part of a
      multidisciplinary treatment approach in a selected group of patients in adequate
      general condition who have pulmonary-limited metastasis that can be completely
      resected.

PMID- 16601391
TI  - The immediate effect of castration on female rabbit bladder blood flow and tissue
      oxygenation.
AB  - BACKGROUND: The female urinary bladder is a target organ for estrogen. Reductions
      in circulating estrogen have been associated with urothelial and vaginal atrophy
      and bladder disorders including incontinence and increased incidence of bladder
      infections. We determined the effect of short-term ovariectomy on sex hormones,
      bladder blood flow, and tissue oxygenation in the rabbit model. MATERIALS AND
      METHODS: Female New Zealand White rabbits were ovariectomized and evaluated on 1,
      3, and 7 days after ovariectomy. Tissue oxygenation (pO2) and blood flow were
      measured with oxylab system of real time measurements. Serum estrogen and
      progesterone were determined at sacrifice. Tissue hypoxia was localized
      histologically using Hypoxyprobe-1 immunohistochemistry. RESULTS: Short-term
      ovariectomy caused rapid decreases in serum estrogen and progesterone,
      significant decreases in urothelial oxygenation and blood flow. No significant
      decreases in blood flow or oxygenation were noted for the detrusor smooth muscle.
      Immunohistochemistry confirmed the presence of urothelial hypoxia at all times
      after ovariectomy. Bladder muscle did not demonstrate significant levels of
      hypoxia. CONCLUSION: The bladder urothelium is extremely sensitive to short-term
      ovariectomy, with significant urothelial hypoxia seen by post-ovariectomy day 1.
      Urothelial hypoxia may play a significant role in pelvic pain syndromes,
      incontinence, and increased susceptibility to bladder infection.

PMID- 16601392
TI  - Expression of epidermal growth factor receptor and proliferative activity of cyst
      epithelium in human renal cystic diseases.
AB  - Pathogenesis of malignancies in patients with polycystic kidney disease (PKD) is
      not clearly understood. Epidermal growth factor receptor (EGF-r) production by
      mature kidney plays a role in promotion of epithelial hyperplasia and cyst
      formation, its involvement in further progression is however not proven. Ki-67 is
      a marker for cellular proliferation. We assessed immunohistochemical expression
      of EGF-r and Ki-67 in epithelium of normal kidney, single cysts without PKD,
      epithelial tubular cells lining simple cysts and cysts with papillary
      proliferation in PKD patients, and analyzed the relationship with the occurrence
      of malignant tumors in these cases. 72% of PKD displayed EGF-r staining in
      epithelium lining cysts versus 33% in normal epithelium and 70% in epithelium of
      normal kidney. Ki-67 was increased in papillary cystic epithelium (24%) and in
      cysts lined by flat epithelium (66%). Renal cancers in PKD showed EGF-r staining
      in 33%, but no Ki-67 expression. EGF-r function and proliferative activity in
      cyst formation in PKD remains to be explored. EGF-r and Ki-67 expressions are not
      predictive of development of carcinoma in PKD.

PMID- 16601393
TI  - Human chorionic gonadotropin deteriorates the histology of rat testes.
AB  - OBJECTIVES: It is not yet certain whether early hormonal treatment in
      cryptorchidism is safe for germ cells. We investigated the histologic effects of
      human chorionic gonadotropin (hCG) therapy on descended testes of rats. DESIGN
      AND SETTING: Thirty male Wistar albino rats were randomized into two groups. The
      rats of the hCG group (n=15) were administered 50 IU/kg/day hCG once daily via
      the subcutaneous route for 15 days. Fifteen rats received subcutaneous isotonic
      saline and acted as controls. At the first month, testicular tissue was obtained
      after scarification in both groups. The histological examination was performed to
      evaluate the seminiferous tubular diameter, germinal membrane thickness, and the
      percentage of the open seminiferous tubule lumen in each testis to compare the
      two groups. RESULTS: The percentage of the open seminiferous tubular lumen in
      testicular tissues of hCG-treated rats was higher than that of controls (p<0.05).
      The mean germinal membrane thickness in testicular tissues of the hCG group was
      statistically lower than that of the control group (p<0.05). There was no
      statistical difference between mean seminiferous tubular diameter in testicular
      tissues of hCG-treated rats and controls, as expected (p>0.05). Additionally,
      there were two interesting cases of Sertoli cell only appearance in the hCG
      group. CONCLUSIONS: We may assume that hCG impairs the seminiferous tubule
      histology in normal testes of rats. Thus, further experimental studies on dose
      dependency and the reversibility of these effects are warranted.

PMID- 16601394
TI  - Cannabis-induced koro-like syndrome. A case report and mini review.
AB  - The genital-shrinking syndrome is a transient state of acute anxiety
      characterized by the triad of a deep-seated fear of penile shrinkage, its
      disappearance into the abdomen, and apprehension regarding inevitable impotence
      or even death. It is also known by the Malayo-Indonesian term 'koro'. In the
      West, koro syndrome has been reported only in relation with various somatic,
      psychiatric and drug-induced disorders. The vast majority of non-psychiatric
      cases was related to neurological disorders or intoxication with cannabis or
      amphetamine. This is the first case of cannabis-induced koro-like syndrome ever
      reported in Greece.

PMID- 16601395
TI  - Irinotecan as a new agent for urachal cancer.
AB  - The urachal carcinoma, in a 64-year-old male with multiple lung metastases, had
      shown the resistance to several anti-neoplastic agents including cisplatinum,
      methotrexate, 5-FU, doxorubicin, epirubicin, and mitomycin C. Because the tumor
      was adenocarcinoma producing mucin and serum carcinoembryonic antigen (CEA)
      increased, which resembled colorectal carcinoma, we administrated Irinotecan,
      which was very effective as the CEA decreased from 98.3 to 38.7 ng/ml and the
      pulmonary metastatic lesions were reduced by 60%. To our knowledge, this is the
      first case with urachal carcinoma in which Irinotecan was effective.

PMID- 16601396
TI  - Dispelling inhibition for laparoscopic surgery in younger children with Cushing's
      syndrome. Case report and literature review.
AB  - Laparoscopic adrenalectomy (LA) is now the gold standard for the treatment of
      small, benign adrenal tumors in adults. In Cushing's syndrome (CS), LA is
      difficult and seldom done, especially in younger children. A 6-year-old girl was
      diagnosed with CS due to a juxtaadrenal tumor. She underwent LA and made an
      uneventful recovery. The histopathology was reported as paraganglioma which is a
      very rare cause of CS. LA is seldom done in younger children with CS owing to
      extreme obesity, abundant perinephric fat and a high incidence of pre- and
      postoperative complications.

PMID- 16601397
TI  - Primary adrenal tuberculosis: role of computed tomography and CT-guided biopsy in
      diagnosis.
AB  - A case of isolated, bilateral, adrenal tuberculosis is presented. A 25-year-old
      male was admitted to the hospital due to lumbar pain, fever, weight loss and
      anorexia. Abdominal ultrasonography and computed tomography demonstrated
      bilateral adrenal enlargement. Laboratory investigations were remarkable for
      adrenal insufficiency. The Mantoux reaction was positive but there was no
      evidence of lung or urinary infection. CT-guided biopsy of the left adrenal gland
      was performed and established the diagnosis of adrenal tuberculosis.

PMID- 16601398
TI  - Re: systemic augmentation of nitric oxide: is there an immediate effect on the
      urinary flow rate in healthy men?

PMID- 16601399
TI  - Child mania rating scale: development, reliability, and validity.
AB  - OBJECTIVE: To develop a reliable and valid parent-report screening instrument for
      mania, based on DSM-IVsymptoms. METHOD: A 21-item Child Mania Rating Scale-Parent
      version (CMRS-P) was completed by parents of 150 children (42.3% female) ages
      10.3 +/- 2.9 years (healthy controls = 50; bipolar disorder = 50; attention
      deficit/hyperactivity disorder [ADHD] = 50). The Washington University Schedule
      for Affective Disorders and Schizophrenia was used to determine DSM-IV diagnosis.
      The Young Mania Rating Scale, Schedule for Affective Disorders and Schizophrenia
      Mania Rating Scale, Child Behavior Checklist, and Child Depression Inventory were
      completed to estimate the construct validity of the measure. RESULTS: Exploratory
      and confirmatory factor analysis of the CMRS-P indicated that the scale was
      unidimensional. The internal consistency and retest reliability were both 0.96.
      Convergence of the CMRS-P with the Washington University Schedule for Affective
      Disorders and Schizophrenia mania module, the Schedule for Affective Disorders
      and Schizophrenia Mania Rating Scale, and the Young Mania Rating Scale was
      excellent (.78-.83). The scale did not correlate as strongly with the Conners
      parent-rated ADHD scale, the Child Behavior Checklist -Attention Problems and
      Aggressive Behavior subscales, or the child self-report Child Depression
      Inventory (.29-.51). Criterion validity was demonstrated in analysis of receiver
      operating characteristics curves, which showed excellent sensitivity and
      specificity in differentiating children with mania from either healthy controls
      or children with ADHD (areas under the curve of.91 to.96). CONCLUSION: The CMRS-P
      is a promising parent-report scale that can be used in screening for pediatric
      mania.

PMID- 16601400
TI  - Test-Retest Reliability of the Preschool Age Psychiatric Assessment (PAPA).
AB  - OBJECTIVE: To examine the test-retest reliability of a new interviewer-based
      psychiatric diagnostic measure (the Preschool Age Psychiatric Assessment) for use
      with parents of preschoolers aged 2 to 5 years. METHOD: A total of 1,073 parents
      of children attending a large pediatric clinic completed the Child Behavior
      Checklist 1 1/2-5. For 18 months, 193 parents of high scorers and 114 parents of
      low scorers were interviewed on two occasions an average of 11 days apart.
      RESULTS: Estimates of diagnostic reliability were very similar to those obtained
      from interviews with parents of older children and adults, with kappas ranging
      from 0.36 to 0.79. Test-retest intraclass correlations for DSM-IV syndrome scale
      scores ranged from 0.56 to 0.89. There were no significant differences in
      reliability by age, sex, or race (African American versus non-African American).
      CONCLUSIONS: The Preschool Age Psychiatric Assessment provides a reasonably
      reliable standardized measure of DSM-IV psychiatric symptoms and disorders in
      preschoolers for use in both research and clinical service evaluations of
      preschoolers as young as 2 years old.

PMID- 16601402
TI  - A randomized, double-blind, placebo-controlled study of modafinil film-coated
      tablets in children and adolescents with attention-deficit/hyperactivity
      disorder.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of modafinil in children and
      adolescents, ages 7 to 17, with attention-deficit/hyperactivity disorder (ADHD).
      METHOD: In this 9-week, double-blind, flexible-dose study, patients were
      randomized to once-daily modafinil (170-425 mg) or placebo. Assessments included
      ADHD Rating Scale-IV (ADHD-RS-IV) School and Home Versions and Clinical Global
      Impression of Improvement (CGI-I) scale. RESULTS: Two hundred patients were
      randomized. Modafinil produced significant reductions in ADHD-RS-IV total scores
      at school (n = 128; mean change +/- SD: -17.5 +/- 13.1 points) compared with
      placebo (n = 66; -9.7 +/- 10.3 points; p < .0001). Similarly, modafinil reduced
      ADHD-RS-IV total scores at home compared with placebo (-17.6 +/- 13.3 versus -7.5
      +/- 11.8 points; p < .0001). Fifty-two percent of patients randomized to
      modafinil and 18% of those randomized to placebo met prestudy criteria for
      responder on the CGI-I (p < .0001). Randomization to modafinil was associated
      with significantly more insomnia, headache, decreased appetite, and weight loss
      than randomization to placebo, but discontinuation attributed to adverse events
      did not differ statistically between treatment groups (modafinil, 5%; placebo,
      6%). CONCLUSION: Modafinil was well tolerated and reduced ADHD symptoms at school
      and home compared with placebo.

PMID- 16601404
TI  - Internal splinting of fractures of the fifth metacarpal. J Bone Joint Surg.
      1937;19:826-7.

PMID- 16601406
TI  - On the fracture of the carpal extremity of the radius. Edinb Med Surg J.
      1814;10:181.

PMID- 16601407
TI  - The classic: injuries of the wrist: a radiological study. New York, NY: Paul B.
      Hoeber; 1926.

PMID- 16601408
TI  - Fracture of the base of the first metacarpal and a variation that has not yet
      been described: 1910. (Translated by Roy A. Meals).

PMID- 16601409
TI  - Plate and screw design in fractures of the hand and wrist.
AB  - As internal fixation of fractures of the hand and wrist has evolved, so too have
      the implants used for the same purpose. Implants used for the first (1/2) of the
      20th century were modeled on implants used to fix long bone fractures.
      Consequently, they were often bulky. In addition, they often were made of
      materials which were ill suited to the unique functional and biomechanical
      requirements of the hand and wrist. As a result, outcomes of internal fixation
      frequently were suboptimal and complication rates were high. In the past 40 years
      there has been an evolution in metallurgy, biomechanics, and implant design for
      fracture fixation in the hand and wrist, quite unlike any other anatomic location
      in the body. The principal purpose of this review is to highlight these very
      advances. Implants now are made of highly bio-compatible materials, have a low
      profile, can be contoured to suit individual anatomy, and provide considerably
      reduced rates of soft tissue irritation. These features afford surgeons the
      ability to fix complex injuries in a stable manner so as to institute early
      rehabilitation in an effort to maximize individual outcomes. LEVEL OF EVIDENCE:
      Level V (expert opinion).

PMID- 16601410
TI  - Effects of implant material and plate design on tendon function and morphology.
AB  - Titanium implants are an alternative to stainless steel implants for internal
      fixation after fracture. The advantages of titanium include decreased implant
      stiffness, increased bio-compatibility, and diminished stress shielding. However,
      titanium has been implicated in tendon irritation and adhesions when used in the
      hand and wrist. We evaluated the relationship between extensor tendon morphology
      and dorsal plating of the distal radius in a canine model using distal radius pi
      plates made of stainless steel, titanium, and titanium alloy with a modified
      ramped edge design. We found marked histologic changes in the tendons and
      surrounding soft tissues including tendon deformation and degeneration
      (fibrillation, cartilage metaplasia, hypocellularity and hyalinization of blood
      vessels), peritendonous adhesions and neovascularity in the parenchyma. Only a
      minimal inflammatory cell infiltrate was identified and was limited to the
      tenosynovium and/or paratenon. No differences were identified between titanium
      and stainless steel implants and those with a ramped design. Although all animals
      lost wrist motion with time, no differences were observed between groups. Our
      results suggest that pi plate placement on the dorsal surface of the distal
      radius may lead to extensor tendon irritation and dysfunction. There is no
      evidence to suggest that this is specifically related to titanium or plate edge
      design.

PMID- 16601411
TI  - Treatment of failed Sauve-Kapandji procedures with a spherical ulnar head
      prosthesis.
AB  - Radioulnar convergence is a painful complication after a Sauve-Kapandji
      procedure, with a reported incidence of 13% to 39%. We evaluated 10 patients with
      painful radioulnar convergence treated with a spherical ulnar head prosthesis
      proximal to the radioulnar fusion mass. At a mean follow-up of 2.6 years,
      patients were evaluated clinically and radiographically to determine whether an
      ulnar head replacement could restore forearm stability, prevent radioulnar
      convergence, and reduce pain. Postoperatively, no patient had subjective
      complaints of radioulnar convergence or clinical signs of distal ulnar
      instability. Pain had improved in all patients. Grip strength, expressed as a
      percentage of the uninjured hand, improved on average from 27% to 55%. Range of
      motion improved in seven patients, worsened in two and remained the same in one.
      Nine of 10 patients returned to their previous occupation with an average working
      capacity of 76%. The prosthesis was stable radiographically in all patients.
      Complications included two fractures of the radioulnar fusion mass and the
      development of painful periprosthetic calcifications in one patient. Placement of
      a spherical ulnar head prosthesis after a Sauve-Kapandji procedure provides
      adequate early results for patients with painful radioulnar convergence. LEVEL OF
      EVIDENCE: Therapeutic study, level IV (case series).

PMID- 16601412
TI  - Minimally invasive management of scaphoid nonunions.
AB  - Not all proximal pole scaphoid nonunions with avascular necrosis require
      vascularized bone graft or a formal open incision. If the distal scaphoid is well
      perfused and the proximal pole can be secured rigidly after percutaneous bone
      grafting, then nonunion repair and healing can proceed. We describe minimally
      invasive techniques that permit fracture site debridement, establishment of
      distal perfusion by central axis reaming, arthroscopic assessment of perfusion,
      percutaneous bone grafting, and rigid internal fixation. As surgeons develop new
      minimally invasive techniques, it is still imperative to continue to base
      treatment on scaphoid nonunion pathology and the key principles in the treatment
      of any non-union. LEVEL OF EVIDENCE: Level V (expert opinion).

PMID- 16601413
TI  - Open and arthroscopic treatment of perilunate injuries.
AB  - Carpal dislocations are rare and complex injuries. Nearly every combination of
      radiocarpal and intercarpal dislocation has been described, but few fit neatly
      into a particular pattern or classification scheme. The injury may be subtle
      clinically and radiographically, and the diagnosis is frequently delayed. Prompt
      recognition, accurate reduction, and stable temporary internal fixation all
      contribute to improved outcomes. Internal fixation techniques depend on the
      pathology imparted on the carpus. Open reduction, arthroscopic, and
      fluoroscopically aided percutaneous techniques can be used to successfully treat
      carpal dislocations. We report our experiences treating perilunate injuries.
      LEVEL OF EVIDENCE: Level V (expert opinion).

PMID- 16601414
TI  - Tendon avulsion injuries of the distal phalanx.
AB  - Mallet injuries are the result of incompetence of the terminal tendon. Most acute
      mallet fingers can be treated by continuous splinting of the distal
      interphalangeal (DIP) joint in extension for 5-6 weeks. Fracture dislocations
      require open reduction and internal fixation. Treatment of chronic mallet
      injuries must be individualized. If there is a flexible swan neck deformity,
      spiral oblique ligament reconstruction is indicated. For a fixed contracture, DIP
      joint arthrodesis is preferred. Profundus avulsion injuries, or jersey finger,
      seen within 10 days of injury require operative reattachment of the profundus
      tendon. Treatment of avulsions more than 10-14 days after injury must be
      individualized and depends on location of the stump (palm vs. digit), time from
      injury, passive mobility of the digit, and individual functional demands. Chronic
      avulsions, where the stump is distal to the proximal interphalangeal joint can
      often be advanced secondarily. Other options include no treatment, stump excision
      with or without DIP joint arthrodesis, or flexor tendon reconstruction with a
      free graft. LEVEL OF EVIDENCE: Therapeutic study, Level V (Expert opinion).

PMID- 16601415
TI  - Factors influencing cup orientation in 500 consecutive total hip replacements.
AB  - We sought to establish the percentage of acetabular components used in total hip
      arthroplasties that were located outside a presumed safe range of cup
      orientation. Data were analyzed to assess whether dislocation in this series was
      different inside and outside that presumed safe zone. We also asked whether
      acetabular cup orientation depended on patient body mass index, the amount of
      preoperative acetabular head coverage, the surgeon, or the use of minimally
      invasive technique. We assessed cup orientation in 500 total hip arthroplasties
      performed at one institution. Of these 500 total hip arthroplasties, 400 were
      done using conventional approaches whereas mini-incisions were used in 100. We
      found 19.8% of cups were oriented outside the presumed safe range for
      inclination, and 11.2% of cups were oriented outside the presumed safe range for
      anteversion. Dislocation was not greater in the group with inclination and
      anteversion outside the presumed safe. Cup orientation was influenced by pre
      operative acetabular head coverage, the surgeon, and minimally invasive
      technique, but not body mass index. Cup variability was greater than expected. It
      was not confined to one surgeon, but to the entire group of surgeons experienced
      in doing total hip replacements. Variability points toward continuous refinement
      in surgical technique and instrumentation to promote consistency in cup
      placement. LEVEL OF EVIDENCE: Prognostic study, Level IV (case series).

PMID- 16601416
TI  - A technique for intraoperative construction of antibiotic spacers.
AB  - A technique for intraoperatively creating an antibiotic spacer for two-stage
      treatment of infected total knee replacements is described. An intraoperative
      mold is made from the removed components and used to create antibiotic spacers
      with surface contours similar to those of the original total knee replacement.
      The spacers restore leg length and knee stability. This allows limited function
      during the interval before reimplantation of the new total knee replacement. It
      is a cost-effective and convenient technique for creating a suitably shaped and
      sized cement spacer for two-stage revision total knee replacement after
      infection. The clinical results of 12 consecutive patients using this technique
      with minimum of 2 years followup seem to be at least equal or better than results
      reported in previous studies. LEVEL OF EVIDENCE: Prognostic study, Level II
      (retrospective study).

PMID- 16601417
TI  - Duration of preoperative traction associated with sciatic neuropathy after hip
      fracture surgery.
AB  - An unknown percentage of patients who have internal fixation for hip fractures
      have sciatic neuropathy develop. In most cases, the cause for this complication
      is unknown. We retrospectively reviewed 2202 consecutive patients treated in our
      hospital for hip fractures to ascertain whether there was any relationship
      between duration of preoperative traction and postoperative sciatic neuropathy,
      and to determine the incidence of sciatic neuropathy after surgery for hip
      fractures. All patients had preoperative skin traction. Patients with and without
      sciatic neuropathy were compared using nonparametric tests. The median duration
      of traction was 2.6 days in the group that had sciatic neuropathy develop and 0.9
      days in the group that did not. Also, patients in the group that had sciatic
      palsy develop were older. There seemed to be no other difference between the
      groups for any of the studied variables. Sixteen patients (0.7 %) had
      postoperative sciatic neuropathy. Our data suggest sciatic neuropathy after
      surgery for hip fractures may be related to the duration of preoperative
      traction. Some investigators have reported that there seems to be no evidence of
      benefit from skeletal or skin traction. A potential for damage to the sciatic
      nerve may be an argument to stop routine use of preoperative traction. LEVEL OF
      EVIDENCE: Diagnostic study, Level III (study of nonconsecutive patients; without
      consistently applied reference "gold" standard).

PMID- 16601418
TI  - Case reports: transient osteoporosis of the hip: an atypical case.
AB  - We present the case report of a 37 year-old woman who had transient osteoporosis
      in her third trimester of pregnancy. The condition spread beyond the hips and
      involved all six major joints of the lower limbs. The polyarticular involvement
      is the first to our knowledge. The condition resolved spontaneously in the usual
      manner during 12 months postpartum. The differential diagnosis is an important
      consideration, as investigation may be limited by concerns for the fetus. This
      includes regional migratory osteoporosis, inflammatory arthritis, septic
      arthritis, avascular necrosis, stress fracture of the femoral neck, synovial
      disorders, and neoplasia. We report the typical results and management of
      transient osteoporosis as a reminder of this uncommon, but impressive condition.

PMID- 16601419
TI  - Case reports: pathologic fracture of the patella from a gouty tophus.
AB  - Fracture of the patella is a relatively common condition seen in patients with
      trauma. We report one patient with known gout who sustained relatively minor
      trauma that resulted in a patellar fracture. An intraoperative biopsy confirmed
      that much of the patella had been replaced with gouty tophus. Gout is a rare
      cause of patellar fracture, with few documented cases. Postoperative management
      of patients with patella fractures secondary to gout may be routine with the
      addition of medical management for the underlying pathologic process.

PMID- 16601420
TI  - Bilateral lower extremity discomfort in a 64-year-old woman.

PMID- 16601421
TI  - Knee pain in a 71-year-old man.

PMID- 16601422
TI  - Shock wave therapy for chronic Achilles tendon pain: a randomized placebo
      controlled trial.

PMID- 16601423
TI  - Selective screening for scoliosis.

PMID- 16601426
TI  - Phase I/pilot study of SU5416 (semaxinib) in combination with irinotecan/bolus 5
      FU/LV (IFL) in patients with metastatic colorectal cancer.
AB  - OBJECTIVES: Determine the toxicity, tolerability, and pharmacokinetics of SU5416,
      a vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase
      inhibitor, coadministered with bolus 5-fluorouracil (5-FU), leucovorin, and
      irinotecan (IFL) in untreated patients with metastatic colorectal cancer.
      METHODS: SU5416 (85 or 145 mg/m2) was administered twice weekly throughout a 6
      week period along with standard IFL (4 weeks on/2 weeks off). Plasma samples were
      assayed for SU5416, irinotecan, and SN-38 by reverse-phase HPLC. Contrast
      enhanced, color Doppler sonography was performed on patients at the MTD to
      identify changes in tumor perfusion. RESULTS: Eleven patients received treatment
      with SU5416 85 mg/m2 (n = 5) or 145 mg/m2 (n = 6). At 85 mg/m2, no DLTs were
      observed. At 145 mg/m2, grade 3 diarrhea and vomiting were observed during cycle
      1; other grade 3 toxicities included fatigue, nausea, anorexia, anemia, pain,
      urinary retention, and hypertension. The pharmacokinetics of irinotecan and SN-38
      were not altered by coadministration of SU5416. SU5416 pharmacokinetics were not
      altered by IFL. Contrast-enhanced, color Doppler sonography was performed on 2
      patients and demonstrated reduced tumor perfusion after treatment in a patient
      who responded to treatment and increased perfusion in a patient who developed
      progressive disease. Three patients (27%) had confirmed partial responses, 2
      patients (18%) had unconfirmed partial responses, and 4 patients (36%) had stable
      disease. CONCLUSIONS: Twice weekly SU5416 can be administered with bolus IFL
      without unexpected toxicities or altering the pharmacokinetic behavior of the
      administered drugs. Changes in tumor blood perfusion can be detected by contrast
      enhanced, color Doppler sonography. The further development of SU5416 was halted
      before this study was completed.

PMID- 16601427
TI  - Phase II trial of gemcitabine plus irinotecan in patients with esophageal cancer:
      a Southwest Oncology Group (SWOG) trial.
AB  - OBJECTIVES: Metastatic esophageal carcinoma is an incurable disease with median
      survival duration of 6 to 8 months. Based on preclinical data suggesting a dose
      dependent synergy between gemcitabine and irinotecan we have conducted a phase II
      trial in patients with advanced or metastatic esophageal carcinoma. METHODS:
      Patient eligibility included a diagnosis of squamous cell or adenocarcinoma of
      the esophagus/gastroesophageal (GE) junction, metastatic or recurrent disease, no
      CNS metastasis, no prior chemotherapy, prior adjuvant/neoadjuvant chemotherapy
      was allowed, no prior gemcitabine or irinotecan, performance status of 0 to 2 and
      adequate organ function. Patients received gemcitabine 1000 mg/m2 and irinotecan
      100 mg/m2 given day 1 and day 8, every 3 weeks. The primary end point was the 6
      month survival rate. The secondary end point was to assess qualitative and
      quantitative toxicities. RESULTS: Fifty-seven eligible patients were accrued.
      There were 4 treatment-related deaths. The primary grade 3 to 4 toxic events were
      diarrhea, dehydration, neutropenia, thrombocytopenia, anemia, and anorexia; and 4
      episodes of grade 3 to 5 febrile neutropenia, 1 fatal. The study was designed to
      detect a difference between the null hypothesis of 30% 6-month survival and the
      alternative hypothesis of 50% 6-month survival. The Kaplan-Meier estimate of 6
      month survival is 56% (95% CI: 43-69%), with a median of 6.3 months. The median
      time to progression was 3.7 months. The 6-month progression-free survival
      estimate is 25% (95% CI: 13-36%). CONCLUSIONS: The length of survival suggests
      that this combination has benefit similar to platinum containing regimens,
      however, the toxicity is substantial and is unlikely to prove superior to
      platinum containing regimens.

PMID- 16601428
TI  - Colorectal cancer in Hispanics: a population at risk for earlier onset, advanced
      disease, and decreased survival.
AB  - BACKGROUND: While colorectal cancer (CRC) incidence and mortality rates have
      declined slightly over the past decade, there remain marked differences by
      ethnicity. Our aim was to investigate ethnic differences in occurrence, clinical
      presentation and outcome of CRC at a tertiary university center that serves a
      predominantly Hispanic population. METHODS: Prospectively collected data from the
      tumor registry on patients diagnosed with colorectal cancer from 1985 through
      2001 was examined. Age at diagnosis, mode of presentation, sex, tumor location,
      ethnicity, TNM stage, and survivals were assessed and ethnic differences were
      sought. RESULTS: Records from 453 patients with CRC were reviewed. There were 296
      (65%) patients that were Hispanics, 112 (25%) non-Hispanic Whites, 37 (8%)
      African Americans, and 8 (2%) of other or unknown ethnicity. Compared with non
      Hispanic Whites, Hispanics presented at a younger age (58.5 +/- 14 versus 53.6 +/
      12.73, respectively; P < 0.01), with a significantly greater incidence of stage
      IV disease (19% versus 32%, respectively; P = 0.02). They had significantly
      poorer age-adjusted survival (median survival of 92 months for <55 years and 77
      months for >55 years versus 48 months for <55 years and 48 months for >55 years,
      respectively; adjusted log rank P = 0.045). There were no differences in tumor
      location, mode of presentation or adjuvant treatment received. CONCLUSIONS:
      Hispanic patients with CRC in our catchment area present at a younger age with
      more metastatic disease and have a poorer survival than non-Hispanic Whites.
      Modification of screening criteria and treatment paradigms may be required for
      Hispanics.

PMID- 16601429
TI  - Combination chemotherapy with gemcitabine and cisplatin as first-line treatment
      for immunohistochemically proven cholangiocarcinoma.
AB  - OBJECTIVES: The aim of this study was to determine the efficacy and safety
      profile of gemcitabine plus cisplatin in patients with immunohistochemically
      proven unresectable cholangiocarcinoma. PATIENTS AND METHODS: Between March 2002
      and December 2004, a total of 24 patients with immunohistochemically proven
      cholangiocarcinoma were entered in this study. Treatment consisted of gemcitabine
      1000 mg/m2 intravenous infusion on day 1 and 8 and cisplatin 70 mg/m2
      intravenously on day 1 every 3 weeks. RESULTS: Seventy-one cycles of treatment
      were given, with a median of 3 cycles (range, 2-6 cycles). Five patients had a
      partial response (PR), 12 patients had stable disease (SD), and 7 patients
      progressed during treatment. A median survival of 9.30 months (range, 6.43-12.17)
      was obtained hematologic and nonhematologic toxicities were generally acceptable.
      However, there was one treatment-related mortality caused by thrombotic
      thrombocytopenia purpura (TTP) associated with gemcitabine and cisplatin.
      CONCLUSIONS: The combination chemotherapy of gemcitabine and cisplatin had a
      modest effect and was a well tolerated treatment of patients with
      immunohistochemically proven metastatic or unresectable cholangiocarcinoma.

PMID- 16601430
TI  - Phase III study of pentosanpolysulfate (PPS) in treatment of gastrointestinal
      tract sequelae of radiotherapy.
AB  - OBJECTIVES: To evaluate the effectiveness of pentosanpolysulfate (PPS) in the
      treatment of gastrointestinal tract sequelae of radiotherapy. METHODS: Eligible
      patients were those with grade 1 to 3 radiation related proctitis, diarrhea
      and/or melena. At least 4 weeks had to elapse since the completion of the
      radiotherapy course. Patients with bleeding diathesis or ulcers, and patients
      receiving anticoagulants or chemotherapy were excluded. Stratification criteria
      included the type of sequelae (proctitis, diarrhea, melena), the severity grade
      and the onset (<3 months post-RT, >3 months post-RT). Patients were randomized to
      one of the following arms: 100 mg PPS 3 times per day (300 mg/day), 200 mg PPS 3
      times per day (600 mg/day), or placebo 3 times per day. If there was no
      improvement in symptoms after 2 months, the protocol treatment was discontinued.
      If the symptoms improved or resolved, the protocol treatment was continued for
      additional 4 months. Patients under treatment were evaluated monthly, than every
      2 to 3 months for the next 18 months. A symptom assessment questionnaire was used
      to measure quality of life endpoints. RESULTS: From June 1999 to March 2001 180
      patients were accessioned from 34 institutions. A total of 168 were analyzable.
      Neither the best observed response within 3 months for the entire population, nor
      the response rate within sequelae category or the quality of life measures
      differed significantly between the 3 arms of the study. CONCLUSION:
      Administration of PPS has not been associated with an improvement in the clinical
      course of radiation related morbidity of the gastrointestinal tract.

PMID- 16601431
TI  - The clinicopathologic significance of the expression of vascular endothelial
      growth factor-C in intrahepatic cholangiocarcinoma.
AB  - OBJECTIVES: Vascular endothelial growth factor-C (VEGF-C) is known to be an
      important lymphangiogenetic factor. Lymphatic spread is a key prognostic factor
      in intrahepatic cholangiocarcinoma (ICC). We studied the expression of VEGF-C in
      ICC tissues to clarify its clinicopathologic significance. METHODS: The
      expression of VEGF-C in surgical specimens obtained from 36 patients with ICC who
      underwent hepatic resection was examined by immunohistochemistry and Western
      blotting. Strong staining was defined as the presence of VEGF-C immunoreactivity
      in at least 50% of the tumor cells. Immunoreactivity in approximately 10% to
      approximately 50% of the tumor cells was considered as weak staining, and less
      than 10% as no staining. RESULTS: Of the 36 patients with ICC, 15 patients
      (41.7%) showed a strong positive result for VEGF-C. Eleven cases (30.6%) were
      negative and 10 cases (27.8%) showed weak immunoreactivity. VEGF-C expression was
      significantly correlated with lymph node metastasis (P = 0.032) and positive
      surgical margin (P = 0.03). Patients who had strong positive staining for VEGF-C
      showed significantly less favorable survival rates compared with patients who had
      negative or weak staining (P < 0.01). Other significant prognostic factors by
      univariate analysis were vascular invasion, lymph node involvement, and positive
      surgical margin. Multivariate analysis demonstrated that strong VEGF-C expression
      (P = 0.028) and vascular invasion (P = 0.021) were independent factors indicating
      poor prognosis. CONCLUSIONS: Our data suggest that VEGF-C expression serves as an
      independent and important prognostic factor in ICC patients, and it may play an
      important role in the lymph node metastasis of ICC.

PMID- 16601432
TI  - A pilot trial of gemcitabine and vinorelbine plus capecitabine in locally
      advanced or metastatic nonsmall cell lung cancer.
AB  - OBJECTIVES: We conducted a pilot study of gemcitabine, vinorelbine and
      capecitabine combination to evaluate its toxicity and efficacy in chemo-naive
      patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC)
      after a short phase IB trial. METHODS: Eligible chemo-naive patients with stage
      IIIB or IV NSCLC received outpatient administration of gemcitabine 900 mg/m2 and
      vinorelbine 25 mg/m2 intravenously on days 1 and 8, every 3 weeks, concurrently
      with capecitabine 1000 mg/m2 given orally twice a day on days 1 to 5 and 8 to 12
      (dose level I), or days 1 to 6 and 8 to 13 (dose level II). RESULTS: Between
      November 2002 and December 2003, 19 patients participated in the study at either
      dose level I (7 patients) or dose level II (12 patients). The maximum tolerated
      dose, defined as the dose at which no more than 1 of 6 patients in a cohort
      experienced a dose-limiting toxicity (DLT) in the first cycle, was not
      established. However, 1 of 7 patients at dose level I, and 2 of 12 at dose level
      II experienced DLTs (ie, grade 3 hepatotoxicity in 2 patients, and grade 3
      febrile neutropenia in 1 patient). In addition, 2 patients experienced treatment
      related pneumonitis requiring mechanical ventilator support after the second
      course of therapy. Objective tumor response was observed in 5 (26.3%) of 19
      patients. Further patient accrual was stopped according to the study design.
      CONCLUSIONS: This 3-drug combination showed disappointing antitumor activity
      against NSCLC with unexpected life-threatening pulmonary toxicity. No further
      investigation of this regimen is recommended for patients with NSCLC.

PMID- 16601433
TI  - Subcutaneous interleukin-2 and interferon-alpha in metastatic renal cell
      carcinoma: results of a French regional experience in Languedoc.
AB  - OBJECTIVES: To assess the efficacy and toxicity of an immunotherapy regimen
      combining subcutaneous (SC) interleukin-2 (IL-2) and interferon-alpha (IFN) in
      patients with metastatic renal cell carcinoma (MRCC). METHODS: The present study
      included 86 patients with MRCC. Data on treatment toxicity and efficacy
      (responses rates and overall survival) were collected on a hospital database.
      Treatment consisted of 6-week cycles repeated every 2 months for a maximum of 3
      cycles. Each cycle included SC IL-2 20 x 10 MIU/m2 3 times/wk on weeks 1 and 4; 5
      x 10 MIU/m2 3 times/wk on weeks 2, 3, 5, and 6, in combination with IFN 6 x 10
      MIU/m2 once weekly on weeks 1 and 4; and 3 times/wk on weeks 2, 3, 5, and 6.
      RESULTS: Seventy (82%) and 71 (83%) patients received more than 80% of the
      planned doses of IL-2 and IFN during the first cycle, respectively. Ten patients
      had to stop therapy before the end of the first cycle because of excessive
      toxicity (7 patients) or rapidly progressive disease (3 patients). Only 17 (28%)
      proceeded to the second cycle. Main toxicities included fever and asthenia in 86
      (100%) patients, nausea/emesis in 83 (96%) patients, skin disorders in 69 (80%)
      patients, hypotension in 56 (65%) patients, and diarrhea in 50 (58%) patients.
      Sixty-seven (78%) patients developed at least one episode of grade 3 toxicity.
      Objective responses were observed in 13 patients, including 4 complete and 9
      partial responses (15%; 95% confidence interval, 9.5-20.5%). After a median
      follow-up of 45 months, the median time to progression was 4 months (range, 1-41)
      and the median survival was 14 months (range, 1-89). CONCLUSIONS: Only a small
      subset of patients with MRCC is likely to benefit from treatment with IL-2 and
      IFN. As toxicity is significant, the refinement of predictive variables for
      sensitivity to immunotherapy is mandatory.

PMID- 16601434
TI  - Chemoradiotherapy for adenoid cystic carcinoma: preliminary results of an organ
      sparing approach.
AB  - OBJECTIVES: A retrospective review of primary chemoradiotherapy (CRT) for adenoid
      cystic carcinoma (ACC) was performed to determine if CRT might be considered as
      an alternative to radiotherapy and/or definitive surgery. METHODS: All treatment
      naive patients with ACC of the head and neck who were treated with definitive
      primary chemoradiotherapy using carboplatinum and paclitaxel at Dana-Farber
      Cancer Institute in 2000 through 2004 were identified. Information on site,
      stage, presenting symptoms, performance status, treatment, toxicity, and follow
      up were collected and tabulated for review. RESULTS: Five patients were
      identified with previously untreated ACC of the head and neck who received
      primary carboplatinum/paclitaxel CRT for unresectability or organ preservation.
      Patients had a median age of 41, 4 had primaries in the paranasal sinuses
      invading the base of skull and 1 had a transglottic laryngeal lesion. All
      patients completed a course of definitive chemoradiotherapy without treatment
      break. Grade 3 mucosal reactions developed during CRT in all patients. With a
      median follow-up of 36 months (range, 20-43) all patients have local regional
      control; 1 patient developed distant metastases at 7 months and is alive at 20
      months. CONCLUSIONS: Preliminary data suggest that carboplatinum/paclitaxel based
      CRT for ACC provides local regional control and is a potential alternative to
      surgery or radiotherapy for patients with locally advanced ACC.
      Carboplatinum/paclitaxel based CRT warrants further study.

PMID- 16601435
TI  - Preliminary investigation of symptom distress in the head and neck patient
      population: validation of a measurement instrument.
AB  - OBJECTIVE: Observations indicate that the acute toxicity of chemoradiation for
      squamous cell carcinoma (SCC) of the head and neck is not the same as that which
      occurs with radiation therapy alone. Thus, the specific aim of this pilot study
      was to estimate the reliability and validity of a modified version of a symptom
      distress scale used to assess the qualitative difference in symptom distress
      between the 2 populations. METHODS: Over a period of 4 months a consecutive
      sample of 56 patients with head and neck cancer were recruited from the
      Department of Radiation Oncology to take part in our pilot study. The Cancer
      Disease and Treatment Concern Scale (CDTCS) was modified by adding 15 additional
      items and called the Head and Neck Distress Scale (HNDS). All dimensions were
      interrogated with at least four questions and a domain score was generated. In
      addition, the Head and Neck Radiotherapy Questionnaire (HNRQ), an established 22
      item multidimensional questionnaire was also administered by interview after
      completion of the HNDS. RESULTS: Fifty-six patients, 32 chemoradiation patients
      (mean age 64 years) completed the HNDS, taking 8 to 10 minutes to complete. The
      HNDS scores correlated well with the HNRQ scores (r = 0.835), demonstrating an
      acceptable level of content and concurrent validity. There was a significant
      difference in the overall HNDS scores between the chemoradiation group and the
      radiation therapy group (ANOVA, P = 0.001). CONCLUSION: The HNDS is a valid
      measure of acute symptom distress and appears able to discriminate between the
      chemoradiation and radiation alone patients. There is considerable variation in
      symptoms that cause these patients distress.

PMID- 16601436
TI  - The prognostic value of telomerase expression in peripheral blood mononuclear
      cells of head and neck cancer patients.
AB  - OBJECTIVE: This study investigates the expression of telomerase in the peripheral
      blood mononuclear cells (PBMCs) of head and neck cancer patients and the
      relationship between the telomerase expression in PBMCs and clinicopathological
      features with prognosis. METHODS: Peripheral blood samples were collected from
      100 head and neck squamous cell cancer patients and 20 normal control group. The
      telomerase activity in peripheral blood mononuclear cells was measured by
      telomerase rapid amplification protocol (TRAP) assay using TRAPeze telomerase
      detection kit. Pearson chi test was used to analyze the correlation of telomerase
      expression with clinicopathologic parameters. Kaplan-Meier method and Cox
      proportional hazards model were used for prognostic analysis. RESULTS: Regarding
      the expression of telomerase in PBMCs of patients, 73 out of 100 (73.0%) were
      found to be positive, and the remaining 27 cases (27.0%) were negative. The
      difference to the telomerase expression of PBMCs in the normal and cancer
      patients was significant (P < 0.001). The expression of telomerase in PBMCs of
      patients was significant correlated with T classification (P = 0.005), N
      classification (P = 0.002), and AJCC stages (P < 0.001). On multivariate
      analysis, N classification (P = 0.007), AJCC stages (P = 0.02), and telomerase
      expression (P = 0.017) showed independent factors associated with poor survival.
      CONCLUSION: The detection of telomerase expression in PBMCs of head and neck
      cancer patients is a simple and very useful molecular marker for the progression
      and prognosis of head and neck cancer.

PMID- 16601437
TI  - Definitive radiotherapy for juvenile nasopharyngeal angiofibroma.
AB  - OBJECTIVES: To update our experience with definitive radiotherapy (RT) for
      juvenile nasopharyngeal angiofibroma (JNA). METHODS: Twenty-two patients received
      definitive RT for advanced JNA between June 1975 and March 2003 and were followed
      from 2.0 to 30.2 years (median, 12.7 years). Total dose ranged from 30 to 36 Gy.
      RESULTS: Twenty of 22 patients (91%) remained locally controlled after RT; both
      patients who developed a local recurrence were salvaged so that the ultimate
      local control rate was 100%. No patient experienced a severe complication.
      CONCLUSION: Patients with advanced and/or recurrent JNA thought not to be
      amenable to complete resection with acceptable morbidity have a high likelihood
      of cure after RT with a low risk of complications.

PMID- 16601438
TI  - Evaluation of HER-2/neu amplification and other biological markers as predictors
      of response to neoadjuvant anthracycline-based chemotherapy in primary breast
      cancer: the role of anthracycline dose intensity.
AB  - OBJECTIVES: The value of HER-2/neu status as a predictor of response to
      anthracycline-based chemotherapy is still a matter of debate. We evaluated the
      contribution of HER-2/neu gene amplification and other biologic markers in
      predicting response to different doses of neoadjuvant anthracycline-based
      chemotherapy. METHODS: Clinical and pathologic records of 115 primary breast
      cancer patients were reviewed. Forty-eight and 67 patients received high
      (doxorubicin > or =20 mg/m2/wk; epirubicin > or =30 mg/m2/wk) and moderate-low
      anthracycline dose intensity regimens, respectively. Pathologic diagnosis,
      hormonal receptor status (HR), Ki67, and HER-2/neu status were assessed on tumor
      samples before neoadjuvant chemotherapy. HER-2/neu was determined by fluorescence
      in situ hybridization (FISH). RESULTS: HER-2/neu amplification was observed in
      29/115 (25%) tumors, 18 from moderate-low-dose and 11 from high-dose group. In
      the univariate analysis, a high Ki67 index (> or =20%) and positive clinical
      axillary nodes were predictive of an objective tumor response (P = 0.033 and
      0.001, respectively). In the multivariate analysis, Ki67 was the only factor
      predictive of response (OR = 3.08, 95% CI = 1.1-8.5, P = 0.03). HER-2/neu status
      was not a factor in predicting objective response to different anthracycline dose
      intensities. The same finding was observed with regards to HR and Ki67.
      CONCLUSIONS: In our series, no significant dose-response relationship was found
      according to HER-2/neu status.

PMID- 16601439
TI  - The incidence of potential interactions between dietary supplements and
      prescription medications in cancer patients at a Veterans Administration
      Hospital.
AB  - OBJECTIVE: The concurrent use of dietary supplements and prescription medications
      is common among patients with cancer. This study examines potential interactions
      between dietary supplements and prescription medications in a Veteran Hospital
      cancer population. METHODS: Eligible patients seen at the Hematology/Oncology
      clinic at the Veterans Administration Medical Center in Cincinnati, OH, were
      administered a survey to determine their use of dietary supplements. Medication
      profiles were compiled from patients' medical charts and pharmacy records. It was
      also noted whether supplementation was previously documented. Potential
      interactions between dietary supplements and prescription medications were
      identified from a literature search of documented interactions. Several
      demographic factors, including age, race, marital status, education and income,
      were assessed for differences between patients found to be at risk for
      interactions and those for whom no risks were identified. RESULTS: Dietary
      supplements were used by 61% of patients. Multivitamins were the most common
      supplement (80.3%) followed by minerals (40.6%) and herbal preparations (24.8%).
      Of the 121 patients taking supplements, 65 patients (54%) reported taking more
      than one. A potential risk for interaction between dietary supplement and
      prescription medication was identified in 12% of patients taking
      supplementations. Three patients were at risk for multiple interactions. Veterans
      who were not currently married were more likely to be at risk for interactions (P
      = 0.024). Only 28% of patients taking dietary supplements had this
      supplementation documented in their medical record. CONCLUSION: Dietary
      supplementation by a veteran cancer population is common. Interactions between
      the supplement and prescription medication is a potential problem. Patient
      physician discussion and documentation of these issues should be systematically
      addressed.

PMID- 16601440
TI  - Evaluation of nutritional status in cancer patients receiving radiotherapy: a
      prospective study.
AB  - OBJECTIVES: The purpose of the present study was to evaluate the nutritional
      status of cancer patients receiving radiotherapy (RT) and to assess the possible
      contributions of nutritional support to patients with malnutrition. METHODS:
      Prospectively, 207 patients referred to our outpatient radiotherapy department
      were included. The patients were classified according to tumor site (head/neck,
      breast, lung, stomach, or colorectal). Nutritional status at the onset, at the
      end of RT, and 3 and 6 months after irradiation was evaluated with the subjective
      global assessment (SGA). All of the patients were supported with additional
      portions of meal or standard enteral feeding formula during and after the
      irradiation period as long as they were in the moderately or severely
      malnourished groups, respectively. RESULTS: At the onset, malnutrition was
      present in 31% of all patients, and it increased to 43% at the end of RT. This
      difference predominated in head/neck cancer patients. Malnutrition ratios in
      head/neck cancer patients at the onset and after RT were 24% and 88%,
      respectively. By a 6-month follow-up, the ratio of patients with malnutrition
      decreased to 8%. Nutritional status of all groups was found to improve during the
      6-month follow-up period, except for the breast cancer group, which included no
      patients with severe malnutrition at any time. CONCLUSION: The results of the
      present study may be helpful in planning an appropriate nutritional support for
      cancer patients undergoing radiotherapy according to the irradiation site.

PMID- 16601441
TI  - The impact of involved field radiation therapy for patients receiving high-dose
      chemotherapy followed by hematopoietic progenitor cell transplant for the
      treatment of relapsed or refractory Hodgkin disease.
AB  - OBJECTIVES: Patients with refractory/relapsed Hodgkin disease (HD) often receive
      high-dose chemotherapy (HDCT) followed by hematopoietic progenitor cell
      transplant (HPCT) as salvage therapy. This study sought to determine if involved
      field radiation therapy (IFRT) in this setting improves patient outcomes.
      METHODS: The records of 65 patients with refractory/relapsed HD who underwent
      HDCT followed by HPCT between September 1988 and October 2003 were
      retrospectively reviewed. Forty-four patients did not receive IFRT and 21
      received IFRT. RESULTS: Thirty-eight patients were alive at the time of analysis
      with a median follow-up of 3.4 years in the no IFRT group and 1.8 years in the
      IFRT group (P = 0.38). IFRT patients were more likely to have bulky disease at
      initial diagnosis (P = 0.05). Progression-free survival (PFS) was similar in the
      2 groups (P = 0.83). Twenty-two patients in the no IFRT group and 5 in the IFRT
      group have died (P = 0.06). Five-year overall survival rates were 55.6% for the
      no IFRT group and 73.3% for the IFRT group (P = 0.16). There was no significant
      difference between the treatment groups regarding mortality in the first 100 days
      after HPCT (P = 0.41), late events (P = 0.26), or failure in sites previously
      involved with disease (P = 0.76). CONCLUSIONS: Although the current study did not
      demonstrate an improvement in PFS with the addition of IFRT to HDCT and HPCT,
      there was a trend toward improved overall survival. The potential benefit of IFRT
      may be underestimated because of the heterogeneity of the treatment groups. The
      use of IFRT was not associated with an increase in the risk of acute mortality or
      late events.

PMID- 16601442
TI  - New approaches in hormone refractory prostate cancer.
AB  - Effective therapeutic options have not existed for prostate cancer progressing
      after androgen deprivation therapy until very recently. Docetaxel based
      chemotherapy has been demonstrated to extend survival in 2 large randomized
      trials. These studies have provided the impetus to combine docetaxel with novel
      biologic agents to further consolidate the gains in long-term outcome. With the
      arrival of exciting agents including vaccines, monoclonal antibodies, bone
      targeted drugs, antisense oligonucleotides, antiangiogenic drugs, and small
      molecule receptor tyrosine kinase inhibitors, the future of prostate cancer
      therapy appears promising.

PMID- 16601443
TI  - Lethal midline granuloma-nasal natural killer/T-cell lymphoma.
AB  - PURPOSE: The purpose of this paper is to discuss lethal midline granuloma (LMG)
      nasal natural killer (NK) T-cell lymphoma (LMG-NTL). METHODS: Literature review.
      RESULTS: LMG is a rare entity that usually arises in the nasal cavity, exhibits a
      male preponderance, and has a wide age range. The majority of LMGs are LMG-NTLs.
      The optimal treatment of LMG-NTL is unclear and is most likely moderate-dose
      radiotherapy. The prognosis for patients with LMG-NTL is significantly worse than
      for patients with other types of head and neck non-Hodgkin lymphomas (NHL). The 5
      year survival rate is approximately 20% but may be higher, depending on whether
      patients with less aggressive forms of NHL are included. Initial local-regional
      disease progression is the predominant pattern of treatment failure. Late
      failures after 5 years are uncommon. CONCLUSIONS: LMG-NTL is a rare nasal NK/T
      cell lymphoma that can be difficult to distinguish from other benign and
      malignant entities. Its clinical course, however, is extremely aggressive. The
      patterns of failure suggest a role for more aggressive local-regional treatment,
      as well as more effective chemotherapy.

PMID- 16601444
TI  - Parathyroid carcinoma on transplanted parathyroid tissue after total
      parathyroidectomy for renal hyperparathyroidism.

PMID- 16601445
TI  - A case of breast carcinoma late metastasis to the kidney.

PMID- 16601446
TI  - High-intensity chemotherapy and rituximab for the treatment of posttransplant
      lymphoproliferative disorder.

PMID- 16601447
TI  - Malignant thymoma associated with fatal myocarditis and polymyositis in a 32-year
      old woman with a history of hairy cell leukemia.

PMID- 16601448
TI  - ACRO meeting focuses on successes and challenges for radiation oncologists.

PMID- 16601450
TI  - Cardiac connexins as candidate genes for idiopathic atrial fibrillation.
AB  - PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained cardiac
      arrhythmia and may cause significant morbidity. Current management strategies
      offer only modest success and may be associated with intolerable drug side
      effects or risk of procedural complications. As with other cardiac arrhythmias,
      the identification of genetic determinants predisposing to atrial fibrillation
      may provide novel molecular targets for drug development. This review discusses
      the role of cardiac connexins in the heart and suggests that genetic defects in
      cardiac connexins may predispose to arrhythmia vulnerability. RECENT FINDINGS:
      Animal models deficient in cardiac connexins demonstrate abnormalities in
      myocardial tissue conduction and vulnerability to re-entrant arrhythmias,
      including ventricular tachycardia and atrial fibrillation. Atrial tissue analyses
      from human patients with atrial fibrillation consistently demonstrate alterations
      in connexin distribution and protein levels, suggesting a role of connexins in
      the perpetuation of the arrhythmia. Most recently, genetic studies of Cx43 and
      Cx40 indicate that genetic variations in these genes may predispose to arrhythmia
      vulnerability in humans. SUMMARY: Current data support the critical role of
      cardiac connexins in mediating coordinated electrical activation and conduction
      through myocardial tissue. Alterations in the tissue distribution or function of
      cardiac connexins may predispose to cardiac arrhythmias, supporting a previously
      proposed hypothesis that cardiac connexins should be considered a major
      therapeutic target in the management of atrial fibrillation.

PMID- 16601451
TI  - Lamin A/C and cardiac diseases.
AB  - PURPOSE OF REVIEW: In this review, we will outline the most recent and
      significant findings on the role of the lamin A/C in cardiac diseases. RECENT
      FINDINGS: Mutations in the lamin A/C gene (LMNA) are associated with numerous
      diseases involving the heart, skeletal muscles, bones, adipose and nervous
      tissues. LMNA is one of the most prevalent genes in dilated cardiomyopathy in
      which it is associated with a high risk of dysrhythmias, sudden death and heart
      failure. Lamins A and C interact with several proteins reflecting their multiple
      functions, some of which are likely still unknown. No abnormalities specific to
      dilated cardiomyopathy are emerging from investigations of striated muscles
      biopsies or fibroblasts from LMNA mutation carriers. An early diagnosis of the
      disease is difficult. Both animal and cellular models tend to confirm that lamins
      A and C play a key role in maintaining the nuclear architecture as well as in
      regulating transcription. SUMMARY: The cardiac phenotype associated to LMNA
      mutations is now much clearer, but the molecular mechanisms underlying cellular
      and tissue specific phenotypes are still puzzling. Systematic mutation screenings
      and cardioverter-defibrillator implantation have been recommended in patients
      with cardiac symptoms.

PMID- 16601452
TI  - The role of molecular autopsy in unexplained sudden cardiac death.
AB  - PURPOSE OF REVIEW: Sudden cardiac death (SCD) is one of the most common causes of
      death, with many attributable to cardiac/coronary abnormalities evident at
      autopsy. A significant number of SCDs, however, particularly in young people,
      remain unexplained following a medico-legal investigation, including autopsy, and
      are referred to as autopsy-negative sudden unexplained death (SUD). Due to
      molecular advances, however, a cardiac channel molecular autopsy may potentially
      provide a pathogenic basis for SUD and establish cause and manner of death.
      RECENT FINDINGS: Over the past decade, five population-based investigations of
      sudden death in young people elucidated the frequency of and causes responsible
      for these tragic events. The most inclusive epidemiologic study concluded that
      nearly 30% of SCDs in young people are autopsy-negative (i.e. SUD) and most
      likely secondary to cardiac channelopathies. Case reports on the post-mortem
      molecular diagnosis of cardiac channelopathies through the use of a molecular
      autopsy have been presented. Recently, a molecular autopsy series of SUD
      identified pathogenic mutations in long QT syndrome and catecholaminergic
      polymorphic ventricular tachycardia-associated genes in over one-third of cases.
      Similar post-mortem cardiac channel genetic testing in a large population-based
      cohort of sudden infant death syndrome has elucidated mutations in 5-10% of
      cases. SUMMARY: With autopsy-negative SUD accounting for a significant number of
      sudden deaths in young people, a new role for the medical examiner is emerging.
      An accurate diagnosis, derived from a molecular autopsy, will guide the
      appropriate initiation of pre-emptive strategies in hopes of preventing future
      tragedies among those left behind.

PMID- 16601453
TI  - Familial orthostatic tachycardia.
AB  - PURPOSE OF REVIEW: Postural tachycardia syndrome is an autonomic disorder
      primarily of younger women. The patient population is heterogeneous, making
      diagnosis and treatment a challenge. A mutation in the norepinephrine
      (noradrenaline) transporter gene prompted further genetic analysis. RECENT
      FINDINGS: Eleven new mutations were found in the human norepinephrine transporter
      gene, although none were directly associated with postural tachycardia syndrome.
      The 5'-flanking -1012C --> T variant of the dopamine beta-hydroxylase gene was
      slightly increased and protection was associated with a reduced incidence of two
      mutations in the endothelial nitric oxide synthase gene, and one in endothelin-1.
      Mutations in other disease-related genes suggest a potential relationship with
      the pathogenesis of postural tachycardia syndrome. Benign joint hypermobility
      syndrome, for example, shares similar autonomic symptoms and is linked to a
      mutation in tenascin-X. Additional genetic findings are discussed as potential
      contributors to vascular health and neurodegeneration. SUMMARY: Genetic testing
      can reveal molecular mechanisms of disease and provide an additional strategy for
      diagnosis and treatment of heterogeneous patient populations such as postural
      tachycardia syndrome. It is quite likely that the pathogenesis of this disorder
      will be attributed to numerous genetic mutations, both subtle and overt.
      Therefore, continued study of the relationships between genotype and phenotype
      are necessary to better understand this syndrome and others with associated
      dysautonomia.

PMID- 16601454
TI  - Molecular genetics of aortic valve disease.
AB  - PURPOSE OF REVIEW: Bicuspid aortic valve is the most common type of cardiac
      malformation and predisposes to aortic valve calcification, which is the third
      leading cause of heart disease in adults. These seemingly temporally disparate
      diseases have been described as having genetic influences but limited data exist
      on the precise genetic causes in humans. Several advances in the molecular
      genetics of aortic valve formation and calcification have recently been
      identified and are described here. RECENT FINDINGS: A large family with autosomal
      dominant aortic valve disease consisting of bicuspid aortic valve and aortic
      valve calcification was studied using genome-wide linkage analysis. This led to
      the identification of a nonsense mutation in NOTCH1 in affected individuals. This
      finding was supported by the discovery of a NOTCH1 frameshift mutation in an
      unrelated family with similar aortic valve disease, suggesting that NOTCH1
      haploinsufficiency was a genetic cause of aortic valve malformations and
      calcification. The NOTCH signaling pathway was linked to a molecular pathway for
      aortic valve calcification, as NOTCH1 was found to repress activation of Runx2 -
      a transcription factor critical for osteoblast cell fate that is up-regulated in
      calcified human aortic valves. SUMMARY: The recent genetic and biochemical
      findings provide novel insights into the molecular and genetic basis for aortic
      valve dysmorphogenesis and calcification. Future studies focusing on the
      identification of additional disease-causing and susceptibility genes will aid in
      the development of prevention strategies. Ultimately, it will be the careful
      dissection of these molecular pathways that will hopefully lead to novel
      therapeutic options.

PMID- 16601455
TI  - Genetic and nutrient determinants of the metabolic syndrome.
AB  - PURPOSE OF REVIEW: The metabolic syndrome is a very common condition that is
      associated with an increased risk of type 2 diabetes mellitus and cardiovascular
      disease. The diverse clinical characteristics illustrate the complexity of the
      disease, involving several dysregulated metabolic pathways and multiple genetic
      targets. The increasing prevalence of obesity heightens the requirement to reduce
      the risk of the metabolic syndrome. In order to understand the aetiology, it is
      critical to appreciate the nature of multiple gene-gene and gene-nutrient
      interactions relevant to the metabolic syndrome. RECENT FINDINGS: Research
      indicates a major role for genetic susceptibility to the metabolic syndrome.
      Nutrition clearly plays an important role in the development and progression of
      the condition. Genetic background can interact with habitual dietary fat
      composition, thereby affecting predisposition to the metabolic syndrome, and may
      also determine an individual's responsiveness to altered dietary fat intake.
      These studies indicate that therapeutic dietary therapy may require a
      'personalized nutrition' approach, wherein a particular genetic profile may
      determine responsiveness of patients to specific dietary fatty acid
      interventions. SUMMARY: Understanding the biological impact of gene-nutrient
      interactions will provide a key insight into the pathogenesis and progression of
      diet-related polygenic disorders. This review explores the hypothesis that
      genetic components of the metabolic syndrome may be modified by dietary fatty
      acid composition.

PMID- 16601456
TI  - Echocardiographic measures of diastolic function in pediatric heart disease.
AB  - PURPOSE OF REVIEW: The past year has seen a continued evolution in the
      echocardiographic assessment of diastolic function in children. This paper
      reviews published studies from the past year that have helped characterize
      diastolic function using echocardiography in children. RECENT FINDINGS:
      Characterization of diastolic function using Doppler and Doppler tissue imaging
      in the normal infant and child was a primary focus of pediatric echocardiographic
      investigation. These technologies appear to hold significant promise as tools to
      improve understanding of diastolic function in the normal child as the heart
      matures. Diastolic function in children with congenital heart disease has also
      been better characterized using these tools, specifically in patients with atrial
      septal defects, tetralogy of Fallot, single ventricle physiology, and following
      cardiac transplantation. Finally, diastolic function in acquired heart disease or
      with systemic disease in the child has been evaluated using echocardiography,
      with recent reports describing findings in children with dilated cardiomyopathy,
      chronic renal disease, obesity, type I diabetes, juvenile rheumatoid arthritis,
      obstructive sleep apnea, and after anthracycline exposure for childhood cancer.
      SUMMARY: Pediatric echocardiography has clearly become the primary tool for
      describing and characterizing diastolic function in infants and children both
      with and without heart disease. It is becoming an important noninvasive diastolic
      monitoring tool that allows serial assessment of pathologic diastolic disease in
      both primary myocardial and systemic disease states.

PMID- 16601457
TI  - Current treatments for congenital aortic stenosis.
AB  - PURPOSE OF REVIEW: Congenital valvar aortic stenosis is a challenging disease
      that often requires repeated palliative procedures. Stenosis can range from mild
      and asymptomatic, not requiring intervention, to severe, as seen in hypoplastic
      left heart syndrome. New advances such as fetal balloon valvuloplasty,
      improvements in the Ross technique, and long-term studies of trans-catheter
      balloon valvuloplasty and surgical valvotomy warrant a review of the outcomes and
      optimal timing of the various interventions. RECENT FINDINGS: Fetal balloon
      valvuloplasty has shown promise. Despite some mortality and morbidity, some
      fetuses are showing significant growth in left ventricular structures, allowing
      biventricular repair. In neonates and infants with congenital aortic stenosis,
      excellent initial results are obtained with trans-catheter balloon valvuloplasty,
      although stenosis resistant to further balloon dilation or regurgitation may
      develop, necessitating surgical intervention. Midterm results from the Ross
      procedure are encouraging, demonstrating low rates of mortality, aortic
      insufficiency and re-intervention. Stenosis of the pulmonary allograft may be
      inevitable, and recent long-term follow-up suggests an increase in aortic
      insufficiency. SUMMARY: While availability of fetal balloon valvuloplasty is
      limited, it has promise for promoting in-utero left ventricle growth and
      improving function. The optimal procedure for infants and neonates is trans
      catheter balloon valvuloplasty. For older patients, the Ross procedure is the
      repair of choice, although more long-term studies are needed to assess the
      natural course of the autograft. Outcomes should improve with advances in
      pulmonary allografts.

PMID- 16601458
TI  - Risk stratification in the asymptomatic child with Wolff-Parkinson-White
      syndrome.
AB  - PURPOSE OF REVIEW: As the safety and efficacy of invasive electrophysiologic
      studies and ablation therapy in pediatrics improves, there has been a greater
      interest in developing adequate risk stratification criteria for the asymptomatic
      pediatric patient with Wolff-Parkinson-White syndrome. This review will discuss
      the recent literature regarding this debate. RECENT FINDINGS: Recent
      retrospective and prospective studies of Wolff-Parkinson-White syndrome in
      asymptomatic pediatric patients have shown that the well established adult
      criteria for risk stratification may not be applicable in children. Both
      symptomatic and asymptomatic children had similar accessory pathway effective
      refractory periods and supraventricular tachycardia inducibility in recent
      invasive electrophysiologic studies. The first attempt at prospective evaluation
      of the use of ablation therapy in asymptomatic adult and pediatric patients with
      the condition has sparked a debate as to the definition of a high-risk patient
      and the utility of ablation in the asymptomatic patient. SUMMARY: It is still
      controversial whether the established criteria for risk stratification in adults
      can be confidently applied to the pediatric patient. The majority of pediatric
      electrophysiologists use invasive electrophysiologic studies for risk
      stratification and selection of appropriate therapy. This clinical practice
      reflects the increasing prevalence and safety of electrophysiologic study and
      ablation. Further studies to better define indications for study and ablation are
      still necessary, however, to define accurate criteria for risk stratification in
      this difficult pediatric problem.

PMID- 16601459
TI  - B-type natriuretic peptide in heart failure.
AB  - PURPOSE OF REVIEW: This review focuses on recent literature pertaining to the
      role of B-type natriuretic peptide (BNP) in heart failure. RECENT FINDINGS: Heart
      failure is a common disorder that is associated with significant mortality and
      morbidity. The diagnosis of heart failure may at times be difficult when using
      conventional tools. The cardiac natriuretic peptides, particularly BNP, have
      evolved to be useful biomarkers in heart failure and other cardiovascular
      disorders. Recent studies have established a close association between plasma BNP
      and the amino-terminal fragment of the BNP prohormone (NT-proBNP) with the
      diagnosis of heart failure and independent prediction of mortality and heart
      failure events. Furthermore, preliminary data from randomized controlled trials
      suggest that knowledge of BNP and/or NT-proBNP level may optimize the management
      of patients with heart failure. Exogenous natriuretic peptide in the form of
      recombinant human BNP (nesiritide) has been shown to improve hemodynamics and
      dyspnea and is approved in the USA and several other countries for the management
      of patients with acute decompensated heart failure. The effect of nesiritide on
      clinical outcome, however, remains unclear. SUMMARY: When used in the appropriate
      clinical settings, BNP or NT-proBNP testing is extremely useful in establishing
      diagnosis and predicting prognosis in heart failure. Nesiritide holds promise in
      the management of patients with acute decompensated heart failure. Large-scale
      randomized controlled trials to evaluate BNP/NT-proBNP-guided therapy are
      currently in progress and studies of the impact of exogenous BNP on clinical
      outcomes in heart failure are likely to be forthcoming.

PMID- 16601460
TI  - Reverse ventricular remodeling: mechanical options.
AB  - PURPOSE OF REVIEW: The aim of this review is to update the cardiovascular
      clinician on the current status of surgical therapies aimed at achieving reverse
      ventricular remodeling. RECENT FINDINGS: Relevant research focusing on mechanical
      options for reverse ventricular remodeling will be referenced and summarized.
      SUMMARY: Heart failure is a tremendous burden on society in terms of both lives
      lost and healthcare costs. Knowledge of both medical and surgical therapies aimed
      at improving ventricular efficiency and reversing ventricular remodeling should
      be in the armamentarium of clinicians treating heart failure patients.

PMID- 16601461
TI  - Nitric oxide signaling in the cardiovascular system: implications for heart
      failure.
AB  - PURPOSE OF REVIEW: The role played by nitric oxide (NO) in cardiovascular
      physiology remains highly controversial. Following the discovery that NO is the
      prototypic endothelium-derived relaxing factor, this signaling molecule was
      implicated as possessing many other biological actions within the cardiovascular
      system, including effects on cardiac contraction, relaxation, and energetics.
      Here, we discuss new concepts regarding NO signaling, its effector pathways, and
      interactions between NO and the redox milieu within a framework of cardiac
      physiology and pathophysiology. RECENT FINDINGS: Major recent insights that have
      advanced understanding of the mechanisms of NO bioactivity include the following.
      (1) NO acts in subcellular signaling compartments or modules. (2) S-nitrosylation
      (covalent modification of cysteine thiol moieties) of proteins represents a
      prototypic second messenger signaling mode in biologic systems. (3) Reactive
      oxygen and nitrogen species work together to facilitate signaling. (4) Disruption
      of physiologic signaling can occur by either increased formation of reactive
      oxygen species or decreased production of reactive nitrogen species, a situation
      of nitroso-redox imbalance. SUMMARY: These insights, which challenge classically
      held views that NO acts as a freely diffusible molecule regulated primarily by
      concentration and exerting signaling primarily through cyclic GMP production,
      offer a new perspective on the pathophysiology and treatment of congestive heart
      failure.

PMID- 16601462
TI  - Prognosis and therapy approaches of cardiac cachexia.
AB  - PURPOSE OF REVIEW: This review focuses on the prognostic implications and
      therapeutic approaches in cardiac cachexia - a syndrome that has been recognized
      for a long time, although it has only received increased attention lately. RECENT
      FINDINGS: Cardiac cachexia is a common and serious complication of chronic heart
      failure and associated with very poor prognosis, yet is often recognized by the
      clinicians only at late stage. Approximately 15% of heart failure patients will
      develop cardiac cachexia, defined by a 6% non-edematous, non-voluntary weight
      loss over a period of 6 months. Several studies have demonstrated that cardiac
      cachexia is a multi-factorial disease, which involves increased neurohormonal
      activity and immune abnormalities, resulting in hormonal and metabolic
      catabolic/anabolic imbalance of the body, leading to the loss of fat and lean
      mass and ultimately death. So far, there are no standardized therapies available
      for this disease. SUMMARY: Cardiac cachexia in heart failure patients is under
      recognized and there is currently no causal therapy available. Several
      interesting treatment options exist, however, which have emerged recently,
      including appetite stimulants, hormones and 'classical' drugs, such as beta
      blockers and ACE inhibitors.

PMID- 16601463
TI  - Cell-based therapy for heart failure.
AB  - PURPOSE OF REVIEW: Chronic heart failure is a leading cause of hospitalization
      and is associated with a poor prognosis. Current therapeutic strategies do not
      address the underlying cause of the disease. Experimental studies have suggested
      that stem cells can exert beneficial effects on the failing heart by
      transdifferentiating into cardiac cell types and/or by providing a source of
      cardioprotective paracrine factors. RECENT FINDINGS: Early cell therapy studies
      in patients with heart failure have explored the suitability of distinct stem and
      progenitor cell populations for cardiac repair and the feasibility of different
      cell delivery methods. Autologous, unfractionated bone marrow cells or skeletal
      myoblasts have been used in the majority of clinical trials so far. One safety
      concern that has arisen from these studies is that myoblast grafts may represent
      an arrhythmogenic substrate. Improvements of regional systolic function and/or
      tissue viability have been reported. Due to the small number of patients in these
      studies and a lack of randomized control groups, meaningful conclusions regarding
      efficacy cannot be drawn at this time. SUMMARY: Cell therapy for patients with
      heart failure is still in its infancy. While early clinical studies suggest that
      stem and progenitor cell transfer to the failing heart may be feasible, firm
      conclusions regarding efficacy cannot be drawn at this time. The cell types that
      have undergone clinical testing so far, i.e. bone marrow cells and skeletal
      myoblasts, cannot promote true tissue regeneration. Further research into cell
      types with true cardiac transdifferentiation capacity is necessary in order to
      realize the prospects of cell therapy in this patient population.

PMID- 16601464
TI  - Diastolic heart failure: a myth.
AB  - PURPOSE OF REVIEW: Until recently, patients with heart failure and preserved
      ejection fraction (HFprEF) have been excluded from nearly all large clinical
      trials in heart failure. Based on the conjecture that this clinical picture of
      heart failure, also known as diastolic heart failure, may be different from other
      forms of heart failure, several recent and ongoing clinical trials have targeted
      more specifically this patient population. The present review critically re
      evaluates the pathophysiological rationale for such trials. RECENT FINDINGS:
      Novel techniques to evaluate cardiac performance have revealed that HFprEF is a
      consequence of significant systolic dysfunction of the ventricular muscular pump
      in the presence of a preserved performance of the ventricular hemodynamic pump.
      Diastolic and systolic heart failure are the mere extremes of a spectrum of
      different phenotypes of one and the same disease. Ongoing research explores the
      various disease modifiers, or protective pathways, that delay the progression of
      remodeling in patients with HFprEF. Although, currently, therapy to improve the
      prognosis of HFprEF is essentially the same as for other forms of heart failure,
      the latter ongoing studies may help, in addition, in developing novel and more
      patient-specific therapeutic strategies in these patients. SUMMARY: HFprEF
      constitutes a heterogenous group of different phenotypes within one continuous
      spectrum reflecting heart failure as one disease entity. No pathophysiological
      basis currently warrants setting up empirical clinical trials based on an
      arbitrary subdivision of patients with heart failure.

PMID- 16601465
TI  - Bibliography. Current world literature. Molecular genetics.

PMID- 16601466
TI  - Recent findings on laser treatment of twin-to-twin transfusion syndrome.
AB  - PURPOSE OF REVIEW: Despite the recent demonstration of the benefit of the primary
      laser over amnioreduction, overall survival is far from optimal (70-80%), and
      therefore diagnosis and management of early and late complications following
      placental surgery became of great importance. RECENT FINDINGS: Laser therapy has
      proven to be better than amnioreduction in treating twin-to-twin transfusion
      syndrome. Miscarriage, preterm premature rupture of the membranes and preterm
      delivery account for more than 20% of perinatal mortality after treatment. In
      those who die despite treatment, recurrence of twin-to-twin transfusion syndrome,
      placental insufficiency or feto-fetal hemorrhage with anemia/polycythemia are
      complications that have to be managed with different secondary therapeutic
      options, such as amnioreduction, cord coagulation, intrauterine transfusion or
      repeat fetoscopy-guided laser. Ex-vivo placental angiography has confirmed that
      these complications occur when anastomoses are missed. Early predictors of laser
      efficacy in twin-to-twin transfusion syndrome treatment, such as improvement in
      the umbilical vein flow imbalance and urine production, are being evaluated,
      because they are earlier predictors of outcome than amniotic fluid discordance.
      SUMMARY: Optimization of laser treatment of twin-to-twin transfusion syndrome and
      new insight into the follow-up are likely to become the key to a better
      prognosis, and they are therefore important issues that have to be addressed in
      forthcoming studies.

PMID- 16601467
TI  - Drugs and the fetus.
AB  - PURPOSE OF REVIEW: Few drugs are licensed in pregnancy, and data on drug use in
      pregnancy are mainly retrospective and uncontrolled. Pregnancy exposure has
      increased recently to new classes of drugs, as they have been shown to be
      effective and well tolerated outside of pregnancy. RECENT FINDINGS: Anti-nausea
      therapies, H2-receptor and proton pump inhibitors appear to be safe. Metformin is
      being trialed for treatment in gestational diabetes and initial reports appear
      encouraging. Concern has been raised about statins in early pregnancy and should
      be avoided. New antiepileptic medication appears effective with low risk of
      abnormality. However, when combined with valproate, risks are still high.
      Selective serotonin reuptake inhibitors for depression appear to be effective,
      with likely low risk for teratogenesis, although neonatal behavioural syndrome
      following their use in the third trimester is a concern. Angiotensin II
      inhibitors should be avoided in the second and third trimesters of pregnancy.
      Smoking cessation programmes need to be reevaluated. SUMMARY: Information about
      safety of drugs and caution about prescribing in pregnancy should continue. Until
      large clinical trials are performed, the risk/benefit ratio of drugs during
      pregnancy will remain uncertain.

PMID- 16601468
TI  - Fetal anaemia as a cause of fetal injury: diagnosis and management.
AB  - PURPOSE OF REVIEW: This review provides up-to-date information on the diagnosis
      and management of fetal anaemia. RECENT FINDINGS: Exciting advances in the field
      of red blood cell isoimmunization are phasing out the need for invasive
      procedures. Rhesus blood group genotyping using fetal DNA in maternal plasma has
      been introduced into clinical practice with remarkable success. The role of
      middle cerebral artery peak systolic velocity in screening for fetal anaemia has
      been confirmed in various causes of fetal anaemia. A recent review of a
      successful Iran national screening programme for thalassaemia provided a timely
      and valuable educational opportunity. The value of intrauterine transfusion as a
      treatment for fetal anaemia was demonstrated by both high success rate and low
      procedure-related pregnancy loss rate. SUMMARY: Fetal anaemia is one of the
      severe fetal conditions that affect the worldwide population. Rhesus
      isoimmunization remains an important health issue despite the recommendation for
      anti-D immunoglobulin prophylaxis and injection after sensitizing events.
      Noninvasive ultrasound diagnostic methods have replaced traditional invasive
      procedures in the assessment of fetus at risk of anaemia due to various causes,
      including red blood cell isoimmunization, parvovirus B19 infection and
      thalassaemia. The increased availability of intrauterine transfusion will help to
      improve the prognosis of these anaemic fetuses.

PMID- 16601469
TI  - Infection and fetal neurologic injury.
AB  - PURPOSE OF REVIEW: Antepartum fetal exposure to infection/inflammation is a more
      important risk factor for brain injury than intrapartum hypoxia in both the term
      and preterm neonate. Such preexisting infection/inflammation might also provide
      the platform for subsequent intrapartum hypoxic-ischaemic damage. This review
      will discuss the complex interaction between fetal inflammatory response and
      neurotoxicity, and focus on the clinical implications of the synergistic
      interaction between infection/inflammation and hypoxia-ischaemia. RECENT
      FINDINGS: Current evidence indicates that inflammatory mediators are directly
      neurotoxic, and also sensitize the fetal brain tissue to a greater magnitude of
      damage by subsequent hypoxia-ischaemia by lowering the threshold at which hypoxia
      initiates neuronal cell apoptosis/cell death. SUMMARY: Further studies are
      urgently needed to characterize the fetuses at risk of damage, the duration of
      exposure required to cause injury, the influence of gestational age and whether
      Caesarean section may be protective. Until then clinicians should maintain a high
      level of surveillance in labours complicated by infection and avoid additional
      exposure to hypoxic-ischaemic insults.

PMID- 16601470
TI  - Fetal hypoxic and ischemic injuries.
AB  - PURPOSE OF REVIEW: The principles of neonatal neurological protection following
      intrapartum hypoxia are briefly reviewed. The physiological principles behind the
      use of cardiotocograph patterns in defining the timing and mechanism of fetal
      hypoxia and injury are then demonstrated. RECENT FINDINGS: Fetal neurological
      injury may result from progressive hypoxemia, acidosis, diminished cardiac output
      and cerebral ischemia, manifested at birth as low Apgar scores, multisystem
      compromise, severe acidosis and encephalopathy. More commonly, however,
      intrapartum injury results from often intermittent, regional ischemia secondary
      to umbilical cord or head compression resulting in hemorrhage or infarction.
      Under these circumstances, the amount of umbilical acidosis and neonatal
      encephalopathy varies and the potential candidate for neuroprotection may escape
      recognition and timely treatment. Selecting infants likely to benefit from
      neuroprotection requires information on the timing, duration and mechanism of
      hypoxia. Neonatal parameters, including low Apgar scores, acidosis, even
      seizures, lack sensitivity and specificity. Cardiotocograph patterns are capable
      of determining the duration, mechanism and severity of hypoxia and occasionally,
      the timing of neurological injury. SUMMARY: Protecting the newborn from the
      neurological consequences of intrapartum hypoxia requires critical definition of
      the mechanism and timing of this exposure. cardiotocograph tracings offer the
      opportunity to refine the selection of candidates for neonatal rescue.

PMID- 16601471
TI  - Shoulder dystocia and injuries: prevention and management.
AB  - PURPOSE OF REVIEW: Shoulder dystocia is an obstetric emergency that is often
      unpredictable and unanticipated. Despite the identification of various clinical
      risk factors, our ability to predict and prevent shoulder dystocia is very
      limited. Effective and timely clinical management is essential to offer the best
      chance of a satisfactory outcome. RECENT FINDINGS: Upon diagnosis of the
      condition, a team working in tandem to resolve the problem is very effective. Use
      of the McRoberts maneuver, application of suprapubic pressure, with an adequate
      episiotomy allow resolution of over 50% of cases, with a low risk of fetal
      injury. Secondary maneuvers include rotation of the shoulders and delivery of the
      posterior shoulder. These are technically more challenging and may be associated
      with a higher risk of fetal injury. More drastic action may be considered in dire
      cases where even secondary maneuvers fail. These include the Zavanelli maneuver,
      symphysiotomy or iatrogenic clavicular fracture. These techniques, while seldom
      required, may be lifesaving in extremely severe cases. SUMMARY: Upon resolution
      of the clinical event, it is essential to document the entire event, and to
      discuss the clinical problem and management with the parents. These actions will
      reduce the risk of medical litigation, and improve patient satisfaction with
      clinical care.

PMID- 16601472
TI  - Head injuries after instrumental vaginal deliveries.
AB  - PURPOSE OF REVIEW: The types, mechanisms and clinical manifestations of head
      injuries (extracranial, cranial and intracranial) after instrumental delivery are
      described along with current evidence of their prevention and management. RECENT
      FINDINGS: Asymptomatic subdural hematomas can occur in up to 6.1% of
      uncomplicated vaginal deliveries. Maternal nulliparity, incorrect placement of
      vacuum extraction cup and failed vacuum extraction are predisposing factors to
      subgaleal hemorrhage. Injuries associated with the vacuum devices may be
      minimized if the recommended limits for a safe traction force are not exceeded.
      There is no difference in the incidence of scalp trauma between vacuum deliveries
      by a rigid plastic cup (Omnicup) and the standard, silastic cup. The use of a
      metal cup may increase the occurrence of head injuries. Protective covers over
      forceps reduce the rates of neonatal facial abrasions and skin bruises. There is
      no difference in the incidence of cephalhematoma comparing a sequential operative
      vaginal delivery and a caesarean section following a failed vacuum delivery.
      SUMMARY: Instrumental vaginal deliveries carry substantial risks. Only
      practitioners who are adequately trained or are under supervision should
      undertake instrumental delivery. The mode of intervention needs to be
      individualized after consideration of the operator's skills and experience and
      the clinical circumstances.

PMID- 16601473
TI  - Uterine rupture.
AB  - PURPOSE OF REVIEW: The increasing rates of primary caesarean section are likely
      to contribute to a rise in the incidence of uterine rupture in developed
      countries. Uterine rupture continues to be an important cause of maternal death
      in less and least developed countries. Recent publications adressing the
      diagnosis, aetiology and management of primary caesarian section are reviewed.
      RECENT FINDINGS: Uterine rupture is commonly associated with vaginal birth after
      caesarean section, although the absolute risk varies according to previous
      obstetric history, gestational age, and induction of labour. Quantification of
      risk for a range of circumstances allows informed counselling of pregnant women.
      Imaging techniques may improve the early detection of uterine dehiscence but in
      the acute setting abnormal fetal heart rate patterns provide early diagnostic
      information. The scale of the problem in less and least developed countries is
      sobering and maternal mortality can be determined by the ability to access basic
      obstetric care. SUMMARY: Uterine rupture remains one of the most frightening
      complications in obstetric care. The risk of its occurrence is likely to increase
      for many parous women, placing the emphasis on counselling and early prediction
      and prevention wherever possible.

PMID- 16601474
TI  - Diagnosis and management of obstetric anal sphincter injury.
AB  - PURPOSE OF REVIEW: The purpose of this review is to outline optimum practice in
      diagnosis and management of obstetric anal sphincter injury. The review focuses
      briefly on prevention of the problem before outlining diagnosis of sphincter
      injury as well as immediate and long-term management of patients who have
      sustained such injuries. RECENT FINDINGS: Increasing vigilance is vital in order
      that sphincter injury is not overlooked; immediate radiological assessment may
      play a role in diagnosis. Optimum anal sphincter repair should be followed by
      oral laxative administration to maintain sphincter integrity. Biofeedback
      physiotherapy and sacral nerve stimulation show great promise in treatment of
      persistent symptoms. Optimum mode of delivery in future pregnancies is not
      clearly defined, and decisions should be individualized. SUMMARY: Because
      obstetric injury to the anal sphincter mechanism cannot always be prevented,
      efforts must focus on limiting its occurrence, documenting its severity and
      providing optimum therapy to women who have sustained it. Management includes
      routine postnatal review of at-risk women and antenatal assessment in future
      pregnancies to limit deterioration in continence after future deliveries.

PMID- 16601475
TI  - Vesicovaginal fistula: obstetric causes.
AB  - PURPOSE OF REVIEW: Obstetric fistula has a devastating impact on the lives of
      women in poor countries. Currently, there is an international campaign by the
      World Health Organisation, United Nations Population Fund and other bodies to
      address this problem. This article reviews recent literature and highlights the
      paucity of evidence-based data. RECENT FINDINGS: Articles on the pathophysiology,
      co-morbidities and sequelae including physical injury to 'multiorgan systems' and
      social consequences associated with obstetric fistula, are discussed. In
      particular, the devastating social, economic and psychological effects on the
      health and well-being, reintegration and rehabilitation are addressed. There is a
      need for prevalence and incidence studies to measure the extent of this problem.
      The creation of well-equipped fistula centres with multidisciplinary teams to
      evaluate patients should be the aim. Expert surgeons and optimal databases with
      personnel to do research will benefit patients. SUMMARY: Prevention should
      involve alleviation of poverty and improvement in education, maternity services
      and health. Research on issues such as persistent stress incontinence following
      fistula closure, management of reduced bladder capacity, best technique for
      fistula repair, role of vaginoplasty, role of early repair in selective obstetric
      fistula, future reproductive function, dermatological management, and social and
      cultural issues must be done to improve women's health.

PMID- 16601476
TI  - First-trimester screening: lessons from clinical trials and implementation.

PMID- 16601477
TI  - Venous Doppler in the assessment of fetal cardiovascular status.
AB  - PURPOSE OF REVIEW: The purpose of this review is to highlight recent developments
      in the Doppler assessment of the fetal venous circulation with special reference
      to clinical applications in the human fetus. RECENT FINDINGS: Doppler evaluation
      of the fetal venous circulation has increased our understanding of fetal
      cardiovascular function. Examples include the regulatory role of the ductus
      venosus in fetal nutrient partitioning and the significance of venous and
      arterial circulatory watershed areas. Alterations in cardiac afterload,
      contractility compliance, intravascular volume status and heart rate modulate
      venous and arterial flow velocity waveforms. Concurrent examination of these
      cardiovascular factors is of great importance in fetal growth restriction,
      complicated monochorionic multiple gestation, fetal hydrops and arrhythmia. In
      these conditions, comprehensive Doppler assessment provides critical diagnostic
      and prognostic information and has a key role in directing interventions.
      SUMMARY: Venous Doppler has added a critical dimension to the understanding of
      fetal cardiovascular pathophysiology. In both health and disease, venous Doppler
      must now occupy a fundamental position in the comprehensive assessment of the
      fetal circulation.

PMID- 16601478
TI  - Magnetic resonance imaging and the detection of fetal brain anomalies, injury,
      and physiologic adaptations.
AB  - PURPOSE OF REVIEW: Magnetic resonance imaging is playing an increasingly
      prominent role in depicting brain maturation, especially gyral formation that
      follows a temporospatial pattern, and in detecting developmental abnormalities of
      the cortex and other brain sectors. Knowledge of the technical advantages and
      limitations of in-utero magnetic resonance imaging techniques, relative to those
      of the postnatal period, is essential to optimize magnetic resonance sequences
      for early diagnosis. This includes an understanding of the changes in both brain
      anatomy and magnetic resonance signals that occur with an increase in gestational
      age. RECENT FINDINGS: Magnetic resonance imaging has evolved has an important
      adjunct in the diagnosis of brain malformations, particularly in the late-second
      or third trimester. Noxious conditions elicit more of a chronic rather than acute
      response in the fetal brain, which differs from that observed postnatally.
      Clinical applications of proton magnetic resonance spectroscopy may help
      elucidate fetal brain maturation and its abnormalities from a metabolic point of
      view. SUMMARY: Indications for fetal brain magnetic resonance imaging have
      increased because of improvements in magnetic resonance techniques and the
      ability to detect subtle changes within the cerebral parenchyma, especially in
      fetuses at increased risk of brain damage.

PMID- 16601479
TI  - Current applications of fetal cardiac imaging technology.
AB  - PURPOSE OF REVIEW: Over the last few years, great progress has been made in
      imaging technology, which is changing the way prenatal visualization of the fetal
      heart is used for diagnosis and therapy. RECENT FINDINGS: This paper reviews
      recent clinical research using these new techniques, namely dynamic three
      dimensional (4D) echocardiography, myocardial Doppler imaging, B-flow
      ultrasonography, endoscopic ultrasound, and magnetic resonance imaging. Of them,
      4D echocardiography is the most significant development and is discussed in
      greater detail. This includes real-time volumetric data acquisition using matrix
      array transducer technology, motion artefact elimination using spatio-temporal
      image correlation, and various display options. The advantages and limitations of
      each are also addressed. SUMMARY: These techniques can provide (1) sequential
      assessment of the entire heart using a full 4D dataset, (2) 4D delineation of
      trabeculation patterns on the ventricular walls, en-face dynamic shapes of
      ventricular septal defects and spatially complex malformations, (3) derivation of
      cardiac indices to myocardial contractility and strain rate by Doppler tissue
      imaging, and/or (4) the use of transoesophageal ultrasound to guide in-utero
      cardiac intervention. All of these techniques expand our ability to evaluate the
      morphology and function of the in-utero heart.

PMID- 16601480
TI  - Comparative genomic hybridization and prenatal diagnosis.
AB  - PURPOSE OF REVIEW: Microarray-based comparative genomic hybridization (array-CGH)
      which detects aneuploidies and submicroscopic deletions and duplications in one
      assay is now offered for genetic diagnosis in children and adults. Its
      application to prenatal diagnosis is still limited, but very promising. We
      predict that array-CGH on fetal DNA obtained through amniocentesis or chorionic
      villus sampling and in the future possibly through noninvasive collection from
      the maternal cervix or blood, will transform the practice of prenatal diagnosis.
      RECENT FINDINGS: The power of array-CGH for genetic diagnosis and gene discovery
      is supported by recent studies. Most arrays for clinical use carry large DNA
      fragments, but alternative designs containing oligonucleotides will move into the
      clinic. Some oligonucleotide arrays can simultaneously analyze DNA copy number
      and single nucleotide polymorphisms, thereby adding potential assessment of
      uniparental disomy and paternity. Recent array-CGH studies have revealed
      extensive interindividual copy number variation of genomic segments,
      unanticipated complexity of apparently balanced translocations, and new
      phenotypes associated with DNA deletions and duplications. These observations
      affect counseling for prenatal diagnosis by array-CGH. SUMMARY: We believe that
      array-CGH will be embraced as a tool for prenatal diagnosis of chromosomal
      defects, but its introduction into clinical practice should proceed with caution
      by experienced laboratories.

PMID- 16601481
TI  - Three-dimensional ultrasound in prenatal diagnosis.
AB  - PURPOSE OF REVIEW: Several technological advances have greatly improved three
      dimensional sonography, which have improved acquisition and display capabilities.
      This review describes these technical changes as well as current applications of
      3D sonography in prenatal diagnosis. RECENT FINDINGS: Recently published papers
      have emphasized the potential of getting a precise 'any plane of choice' from a
      three-dimensional volume, as a new way of scanning, based on the off-line
      analysis of a volume dataset. Surface mode has been used to demonstrate
      malformations and genetic diseases. The maximum rendering mode, which highlights
      bones, has great potential for imaging the nasal bones and the frontal bones with
      the metopic suture. Organ volume can be measured, but the utility of this in
      clinical practice remains to be determined. Three-dimensional ultrasound needs to
      be standardized. SUMMARY: Three-dimensional ultrasonography is the most rapidly
      developing technique in fetal imaging. New features will permit the transition
      from the era of 'sonography in two-dimensional planes' to 'volume ultrasound'.

PMID- 16601482
TI  - Prenatal intervention for isolated congenital diaphragmatic hernia.
AB  - PURPOSE OF REVIEW: We aim to review the recent literature regarding early
      prenatal prediction of outcome in babies diagnosed with isolated congenital
      diaphragmatic hernia, as well as results of fetal therapy for this condition.
      RECENT FINDINGS: Current survival rates in population-based studies are around 55
      70%. Highly specialized centers report 80% and more, but discount the hidden
      mortality, mainly in the antenatal period. Fetuses presenting with liver
      herniation and a lung-to-head ratio of less than 1.0 measured in midgestation
      have a poor prognosis. Other volumetric techniques are being evaluated for use in
      midtrimester. Recently, a randomized trial failed to show benefit from prenatal
      therapy, but lacked power to document the potential advantage of prenatal therapy
      in severe cases. We proposed percutaneous fetal endoluminal tracheal occlusion
      with a balloon at 26-28 weeks through a 3.3 mm incision. In severe cases, fetal
      endoluminal tracheal occlusion increased lung size as well as survival, with an
      early (7 day) survival, late neonatal (28 day) survival and survival at discharge
      of 75, 58 and 50%, respectively, comparing favorably with 9% in contemporary
      controls. Airways can be restored prior to birth improving neonatal survival
      (83.3% compared with 33.3%). The procedure carries a risk for preterm prelabour
      rupture of the fetal membranes, although that may decrease with experience.
      SUMMARY: Fetuses with severe congenital diaphragmatic hernia can be identified in
      the second trimester. Fetal endoluminal tracheal occlusion can be considered as a
      minimally invasive fetal therapy, improving outcome in such highly selected
      cases.

PMID- 16601483
TI  - Endocervical fetal trophoblast for prenatal genetic diagnosis.
AB  - PURPOSE OF REVIEW: For over a decade, methods of first-trimester, noninvasive
      prenatal genetic diagnosis have been actively pursued by many investigators.
      Isolation of fetal trophoblast from endocervical specimens remains an attractive
      approach, given the greater numbers of fetal cells than in maternal blood and the
      better potential for fetal-cell identification based on markers specific for a
      single cell type (trophoblasts). RECENT FINDINGS: Current studies demonstrate
      feasibility in identification and molecular analysis of fetal trophoblast cells
      for prenatal genetic testing. Sampling methods involving lavage, cytobrush, or
      aspiration of cervical specimens, however, have limitations in the recovery of
      trophoblasts. SUMMARY: Clinical applications await further systematic studies to
      determine safety and accuracy in recovery.

PMID- 16601484
TI  - Bibliography. Current world literature. Maternal-fetal medicine.

PMID- 16601486
TI  - Strategies for prevention of nosocomial sepsis in the neonatal intensive care
      unit.
AB  - PURPOSE OF REVIEW: Infants hospitalized in the neonatal intensive care unit,
      particularly preterm infants, have very high rates of nosocomial sepsis (also
      referred to as late onset sepsis or healthcare-associated sepsis). Today's
      preventive strategies for nosocomial sepsis focus on augmenting the immunologic
      and functional immaturities of premature infants and ameliorating the risks of
      extrinsic factors by the use of prophylactic antibiotics and best clinical
      practices. RECENT FINDINGS: Topical emollients improved neonatal skin condition,
      but were associated with an increased risk of nosocomial bacterial sepsis and
      coagulase negative staphylococcal infections, and thus should not be used in
      extremely-low-birth-weight infants. Single-center studies have shown that
      probiotics containing anaerobic bacteria may reduce the rate of necrotizing
      enterocolitis, the severity of necrotizing enterocolitis, and/or bacterial
      sepsis. Single-center studies have shown that prophylactic fluconazole reduces
      the rates of invasive candidiasis and/or colonization of extremely-low-birth
      weight infants. Quality improvement projects to improve adherence to appropriate
      hand hygiene and best practices for central venous catheter insertion and
      maintenance can reduce rates of nosocomial sepsis. SUMMARY: The safety and
      efficacy of probiotics and prophylactic fluconazole require large multicenter
      trials. Quality improvement initiatives, however, can be performed now and can
      reduce the rates of nosocomial sepsis in the neonatal intensive care unit.

PMID- 16601487
TI  - Inhaled nitric oxide therapy in premature newborns.
AB  - PURPOSE OF REVIEW: Inhaled nitric oxide therapy reduces the need for
      extracorporeal membrane oxygenation in near-term and term newborns with hypoxemic
      respiratory failure and persistent pulmonary hypertension, and is now a standard
      of care for this population. There is also considerable interest, however, in the
      potential role of inhaled nitric oxide in premature newborns with hypoxemic
      respiratory failure. The purpose of this review is to summarize the results of
      clinical trials of inhaled nitric oxide in premature newborns, with particular
      emphasis on studies published in the last 12 months. RECENT FINDINGS: Several
      trials of inhaled nitric oxide in premature newborns with respiratory failure
      have been published in the last year. Interpretation of the findings is
      complicated by differences in the severity of illness of the study populations,
      the trial designs, and relevant outcome measures recorded. SUMMARY: Trials of
      inhaled nitric oxide in premature newborns have yielded conflicting results to
      date, and the role of inhaled nitric oxide therapy in this population remains
      controversial. The largest trials of inhaled nitric oxide therapy in premature
      newborns have completed enrollment but have yet to be published. The results of
      these ongoing trials will help clarify the potential risks and benefits of
      inhaled nitric oxide therapy in the premature newborn.

PMID- 16601488
TI  - Strategies to prevent neuronal damage in paediatric bacterial meningitis.
AB  - PURPOSE OF REVIEW: The mortality of bacterial meningitis can reach 30%, and up to
      50% of survivors suffer from persisting neurological deficits as a consequence of
      the disease. The incidence of neurological sequelae of bacterial meningitis has
      not improved over the last decade. Adjunctive therapeutic options are limited,
      and ongoing research into the pathophysiology of brain damage in bacterial
      meningitis aims at providing the scientific basis for future development of more
      efficient adjunctive options. RECENT FINDINGS: In a population with good access
      to health care, dexamethasone given before or at the time of initiation of
      antibiotic therapy acts beneficially in paediatric pneumococcal meningitis, but
      not in meningococcal meningitis. In experimental animal models, brain-derived
      neurotrophic factor protected against brain injury and improved hearing while
      melatonin, which has antioxidant properties among other effects, reduced neuronal
      death. Transgene technology can be used to provide new insights into the
      pathophysiology of the disease and to identify potential therapeutic targets.
      SUMMARY: Although dexamethasone improves outcome of bacterial meningitis under
      defined circumstances, the morbidity of bacterial meningitis still remains
      unacceptably high. Experimental models may help to identify new therapeutic
      strategies to further improve the neurological outcome in young children
      suffering from bacterial meningitis.

PMID- 16601489
TI  - Perinatal infections, prematurity and brain injury.
AB  - PURPOSE OF REVIEW: The association between perinatal infection and brain injury
      is widely accepted but a cause-and-effect relationship has not yet been proven.
      This article summarizes available evidence and current primary publications for
      debate. RECENT FINDINGS: Work completed during the review period has reinforced
      current understanding of perinatal infection, prematurity and brain injury. In
      animal experiments: lipopolysaccharides have been further implicated in brain
      injury, not only as a cause of brain injury but also as mediators of
      preconditioning and protection. Recent studies suggest that cerebral injury
      following low-dose lipopolysaccharide administration may become compensated in
      adulthood. Other studies have emphasized the complexity of the response by
      showing that plasma cytokine levels may not reflect those in the central nervous
      system or inflammatory events in the brain. SUMMARY: Perinatal infection and
      maternofetal inflammation is strongly associated with preterm birth. Inflammation
      probably represents an important mechanism for cerebral damage, and both overt
      lesions and maldevelopment can result. Epidemiological data and multiple animal
      models to link infection, inflammation and brain damage exist, but proof of
      causation is elusive.

PMID- 16601490
TI  - Diagnostic markers for neonatal sepsis.
AB  - PURPOSE OF REVIEW: To review the current evidence on the use of infection markers
      for diagnostic evaluation of sepsis in neonates. RECENT FINDINGS: Recent research
      in immunology has led to the discovery of cell surface antigens, chemokines,
      cytokines and acute phase proteins that can potentially be used to 'rule in' or
      'rule out' sepsis. The diagnostic utilities of key inflammatory mediators,
      including CD11b, CD64, interleukin-6 and interleukin-8, are promising and likely
      to become increasingly used as markers of infection for both diagnostic and
      prognostic purposes. SUMMARY: Serial measurements and use of combinations of
      markers have been reported to improve sensitivity and negative predictive value
      of these tests. Current markers are not infallible, however, and do not permit
      neonatologists to withhold antibiotics in sick infants with suspected infection.
      Thus, many have emerged as useful indicators for early discontinuation of
      unnecessary antimicrobial therapy. Some infection markers are also useful for
      identifying infants with severe infection and adverse prognosis. Advances in flow
      cytometry have allowed simultaneous measurement of key markers using only minimal
      blood volume. Judicious selection of a panel of markers with complementary
      properties could greatly increase the ability of neonatologists to diagnose
      infection and discern valuable prognostic information.

PMID- 16601492
TI  - Acute urinary tract infection--evaluation and treatment.
AB  - PURPOSE OF REVIEW: The evaluation and management of urinary tract infections in
      infants and children is undergoing changes due to the impact of evidence-based
      studies and new technology. RECENT FINDINGS: The uncircumcised male infant is at
      increased risk for a urinary tract infection, but there is marked difference in
      the frequency of circumcision carried out to lower the risk of infection in the
      United States compared with Europe. Commentaries presenting different
      interpretations of the current data make for interesting reading and present the
      many sides of this issue. Vesicoureteric reflux, previously viewed as the major
      risk factor for acquired renal damage, now shares this role with nonreflux
      nephropathy. Procalcitonin has been evaluated as a biochemical tool to identify
      patients at risk for kidney damage, with dimercaptosuccinic acid scintigraphy as
      the reference method to detect renal scarring. SUMMARY: The previously accepted
      concept that vesicoureteric reflux as detected radiologically is almost always
      the key factor in acquired renal injury secondary to a urinary tract infection is
      no longer accepted. Current studies show that nonreflux nephropathy occurs as
      often as reflux nephropathy. There is now a question of the value of imaging
      studies designed to identify vesicoureteric reflux and of the use of suppressive
      antibiotics for vesicoureteric reflux. There exist useful evidence-based studies
      for antibiotic therapy for upper and lower tract urinary tract infections, but no
      such data are available for guidance in selecting imaging studies for the infant
      or child with a first febrile urinary tract infection.

PMID- 16601493
TI  - Diagnosis and management of dysfunctional voiding.
AB  - PURPOSE OF REVIEW: This review will focus on the diagnosis and management of
      voiding dysfunction in neurologically and anatomically normal children. The
      discussion will highlight recent developments and research in the clinical
      approach as well as the etiology and classification of these disorders. RECENT
      FINDINGS: Voiding dysfunction in children encompasses a wide spectrum of clinical
      entities, recently classified collectively as dysfunctional elimination
      syndromes. Voiding dysfunction typically presents after toilet training and may
      originate from behavioral issues that arise around this time in childhood
      development. The spectrum of disorders includes urge syndrome, dysfunctional
      voiding with an uncoordination between the detrusor and urinary sphincter, and
      enuresis. Clinical symptoms may vary from mild incontinence to severe disorders
      with endpoints of irreversible bladder dysfunction with vesicoureteral reflux,
      urinary tract infection and resulting nephropathy. Diagnosis relies heavily on a
      good history and physical examination, but also includes radiologic and
      urodynamic evaluation. Treatment generally consists of medical therapy, primarily
      with anticholinergics as well as behavioral therapy to modify learned voiding
      patterns that contribute to the voiding dysfunction. SUMMARY: This overview of
      voiding dysfunction in children outlines the established approaches to its
      diagnosis and treatment and highlights the most recent developments in the field.

PMID- 16601494
TI  - Pathogenesis of urinary tract infection: an update.
AB  - PURPOSE OF REVIEW: Urinary tract infection is the second most common bacterial
      infection in children. It may cause renal scarring leading to secondary
      hypertension and chronic kidney disease. Recent information has greatly improved
      our understanding of the pathogenesis of urinary tract infection and renal
      scarring. RECENT FINDINGS: Urothelium, an anatomical barrier for innate immune
      responses, expresses toll-like receptors with the capacity to recognize pathogen
      associated molecular patterns. Engagement of toll-like receptors can lead to
      uroepithelial cell activation and production of inflammatory mediators. These
      include complement proteins, other bactericidal peptides, cytokines, chemokines,
      defensins and adhesion molecules. The resulting inflammatory infiltrate serves to
      aid bacterial clearance but can also lead to renal damage. Furthermore,
      interactions between urinary proteins, such as Tamm-Horsfall protein, and TLR-4
      add to the complexity of this defense system. Interindividual variability in
      cellular response may in part be responsible for variable clinical outcomes.
      Polymorphisms in a number of candidate genes in this host defense mechanism may
      be involved in determining those patients who are susceptible to recurrent
      infections and renal scarring following urinary tract infection. SUMMARY: Further
      understanding of the basic molecular mechanisms of urinary tract infection and
      translating these bench data to the bedside holds the promise of improving
      diagnosis and therapeutic strategies of treating urinary tract infection and
      preventing recurrence and renal scarring.

PMID- 16601495
TI  - Pathogenesis of renal injury in obstructive uropathy.
AB  - PURPOSE OF REVIEW: This review focuses on recent advances in understanding the
      factors contributing to obstructive nephropathy, the most important cause of
      renal failure in children. The major focus is on renal cellular and molecular
      events, with emphasis on those affecting the developing kidney. RECENT FINDINGS:
      Experiments in the fetal sheep or neonatal rat, mouse, or pig reveal dramatic
      effects of urinary tract obstruction on renal growth and development. Surgical
      relief of obstruction can reverse some of the structural and functional deficits,
      but cannot restore normalcy. Renal tubular apoptosis is a major factor leading to
      tubular atrophy following unilateral ureteral obstruction. Increased reactive
      oxygen species, and a renal environment favoring pro-apoptotic, over survival,
      signals, contribute to cell death. A variety of intrarenal factors lead to
      progressive interstitial fibrosis, including the newly described process of
      epithelial-mesenchymal transition, whereby tubular epithelial cells are
      transformed into activated fibroblasts. A number of endogenous antifibrotic
      counter-regulatory molecules have been identified, opening the possibility of
      enhancing the kidney's own defenses against progressive fibrosis. SUMMARY: The
      renal response to urinary tract obstruction is complex and involves a wide array
      of interacting molecules. Elucidation of these interactions will lead to the
      identification of biomarkers that will allow a more precise prediction to the
      response to surgical intervention and, hopefully, to novel therapies to prevent
      renal deterioration.

PMID- 16601496
TI  - The renin-angiotensin system in the development of the congenital anomalies of
      the kidney and urinary tract.
AB  - PURPOSE OF REVIEW: Recognition of the dramatically expanded functional repertoire
      of the renin-angiotensin system now includes a role in morphogenesis of the
      kidney and urinary tract. On the basis of published data, the article presents
      formulations of mechanisms through which the system operates. RECENT FINDINGS:
      Studies in humans and animals carrying defective angiotensin-related genes have
      provided unequivocal evidence that the renin-angiotensin system is involved in
      the normal development of both the kidney and the urinary tract. Angiotensin
      exerts its function through at least two different types of receptors, AT1 and
      AT2. AT1 mediates establishment of the ureteral peristaltic machinery, while AT2
      mediates the early kidney and urinary tract morphogenesis. Disruption in receptor
      functions promotes development of congenital anomalies of the kidney and urinary
      tract. SUMMARY: Angiotensin is involved in multiple steps of normal development
      of the kidney and urinary tract through two types of receptors. This takes place
      in concert with other functionally overlapping genes.

PMID- 16601497
TI  - Recent developments in tissue engineering and regenerative medicine.
AB  - PURPOSE OF REVIEW: Currently, patients suffering from diseased and injured organs
      are treated with transplanted organs or cells. There is, however, a severe
      shortage of donor tissues and organs that is worsening yearly given the aging
      population. This paper reviews recent advances that have occurred in regenerative
      medicine and describes applications of new technologies to treat diseased or
      damaged organs and tissues. RECENT FINDINGS: Most current strategies for tissue
      engineering depend upon a sample of autologous cells from the diseased organ of
      the patient. Biopsies from patients with extensive end-stage organ failure,
      however, may not yield enough normal cells. In these situations, stem cells are
      envisioned as being an alternative source. Stem cells can be derived from
      discarded human embryos (human embryonic stem cells), from fetal tissue or from
      adult sources (bone marrow, fat, skin). Therapeutic cloning offers a potentially
      limitless source of cells for tissue engineering applications. SUMMARY:
      Increasingly, scientists in the fields of regenerative medicine and tissue
      engineering have applied the principles of cell transplantation, material science
      and bioengineering to construct biological substitutes that will restore and
      maintain normal function in diseased and injured tissues.

PMID- 16601499
TI  - Iron: not a benign therapeutic drug.
AB  - PURPOSE OF REVIEW: This article reviews the pathophysiology and clinical
      presentation of iron poisoning. Recently proposed guidelines for triage of
      children with iron ingestion will be discussed as well as diagnostic and
      treatment modalities. Finally, the potential impact of unit-dose packaging as a
      primary preventative measure will be discussed. RECENT FINDINGS: Carbonyl iron
      has a greater safety margin than the iron salts. There have been no published
      reports of serious or fatal poisoning from the ingestion of carbonyl iron
      products. Evidence-based consensus guidelines have determined that the threshold
      for referral to a healthcare facility is 40 mg/kg of elemental iron in the form
      of adult iron formulations. Unit-dose packaging of iron preparations appeared to
      decrease the number of exposures to iron and deaths in the United States during
      the period they were instituted. SUMMARY: Iron poisoning remains primarily a
      clinical diagnosis, although certain laboratory and radiological testing may
      provide helpful evidence to guide evaluation and management. Primary prevention
      is the best modality for decreasing morbidity and mortality for all poisonings
      including iron.

PMID- 16601500
TI  - Mosquito repellents and superwarfarin rodenticides--are they really toxic in
      children?
AB  - PURPOSE OF REVIEW: In many United States households, there are many substances
      used to control the exposure of our children to mosquitoes, mice and rats. This
      review provides information on common mosquito repellents and rodenticides used
      in households and discusses their toxicity, in order to help pediatricians better
      advise their patients of their proper use. RECENT FINDINGS: A recent study has
      demonstrated that many continue to have practices of applying DEET (N,N-diethyl-3
      methylbenzamide) based repellents that may lead to undesirable effects. Picaridin
      and oil of lemon eucalyptus are two products that have recently been shown to
      have an efficacy similar to that of DEET-based repellents. Studies within the
      last five years show that most unintentional superwarfarin ingestions can be
      managed at home with close outpatient follow-up. There does not appear to be a
      benefit of prophylactic vitamin K or gastrointestinal decontamination in patients
      with relatively small ingestions of superwarfarins. SUMMARY: With education and
      correct usage, mosquito repellents and the superwarfarin rodenticides can help
      protect children from significant vector-borne diseases. Not all exposures lead
      to significant morbidity or mortality. With recognition of the current
      literature, most of these exposures can be managed safely at home or as an
      outpatient, ultimately saving healthcare costs.

PMID- 16601501
TI  - Efficacy, abuse, and toxicity of over-the-counter cough and cold medicines in the
      pediatric population.
AB  - PURPOSE OF REVIEW: Over-the-counter cough and cold medicines are widely
      prescribed by general pediatricians in order to relieve cough and other symptoms
      in the setting of upper respiratory infections. This article will review the
      pharmacologic components found in over-the-counter cough medicines, the data
      concerning their use and efficacy in children, the increasing trend of abuse of
      these medications, and their potential toxicity. RECENT FINDINGS: There is an
      overall paucity of data evaluating the use of over-the-counter cough medicines in
      children as well as a lack of evidence for their efficacy. The articles cited
      will review the efficacy of over-the-counter cough medicines, the emerging trend
      of abuse of certain preparations such as dextromethorphan, and specific cases of
      morbidity and even mortality. SUMMARY: According to the limited data that exist,
      there is not any evidence that over-the-counter cough and cold medicines are
      effective in children. In otherwise healthy children without chronic complicating
      factors such as asthma, the symptoms of acute upper respiratory infections are
      generally mild and self-limited. Pediatricians must weigh the benefits against
      the potential risks of recommending over-the-counter cough medicines and should
      be prepared to educate parents about the expected natural course of their child's
      illness and the likelihood that these medications will be minimally effective in
      relieving symptoms, if at all.

PMID- 16601502
TI  - Attention deficit/hyperactivity disorder: complexities and controversies.
AB  - PURPOSE OF REVIEW: Attention deficit/hyperactivity disorder continues to be a
      prevalent childhood behavioral disorder, with significant clinical and media
      interest. Providers must be current with research findings that impact the
      evolving understanding of this complex entity. This article summarizes recent
      progress in our view of attention deficit/hyperactivity disorder, with emphasis
      on controversies around diagnosis and treatment, and future management
      directions. RECENT FINDINGS: Literature about attention deficit/hyperactivity
      disorder in 2005 further enhanced our understanding of the genetic contribution
      to the expression of attention deficit/hyperactivity disorder, with exploration
      of sophisticated genetic models and their dynamic interaction with exposures and
      experiences. Previous literature focuses on conventional treatment; new
      developments in pharmacological/alternative options add to treatment choices, but
      have brought well publicized controversies. Furthermore, optimal management
      continues to gain evidence-based support. SUMMARY: Attention
      deficit/hyperactivity disorder is a subject of great interest to families,
      providers, researchers, and public forums. Scientific investigation supports a
      primary genetic contribution, but the relationship of molecular bases and
      environmental exposures appears intricate and complex. With increased awareness
      of this disorder, diagnostic dilemmas and medication side effects are more widely
      understood, topics particularly important to clinicians. Stimulant treatment
      remains the mainstay of intervention, but new delivery forms and nonstimulant
      options are potential therapies as well.

PMID- 16601503
TI  - Unexplained infant and child death: a review of sudden infant death syndrome,
      sudden unexplained infant death, and child maltreatment fatalities including
      shaken baby syndrome.
AB  - PURPOSE OF REVIEW: This review will examine the most recent published literature
      on Sudden Infant Death, Sudden Unexplained Infant Death, infant and child death
      due to maltreatment, and Shaken Baby Syndrome. RECENT FINDINGS: New
      recommendations from the American Academy of Pediatrics about the evaluation and
      prevention of possible Sudden Infant Death Syndrome cases were published this
      year, with a focus not only on the Back to Sleep campaign, but other factors that
      may contribute to the risk of Sudden Infant Death Syndrome. Additionally, the
      controversial issue of bed sharing is addressed, with advice given not to bed
      share in the first 3 months of life. The possibility of a second sudden infant
      death within a family is discussed. Attention is also paid to the importance of
      considering inflicted injury in the differential diagnosis of every unexplained
      infant or child death, and the recent literature on child maltreatment deaths is
      reviewed. SUMMARY: The grieving family who has lost an infant should receive
      immediate attention and support, and a multidisciplinary investigation team
      should be involved as soon as possible so that a full investigation can take
      place. Investigation of unexplained infant or child death should always involve a
      thorough interview with all adults involved, as well as a proper scene
      investigation and post-mortem examination.

PMID- 16601504
TI  - Update on child physical abuse, sexual abuse, and prevention.
AB  - PURPOSE OF REVIEW: The most recent literature regarding assessment and management
      of child maltreatment will be considered. The current status of abuse prevention
      activity will also be reviewed. RECENT FINDINGS: Clinical practice continues to
      be burdened by the general lack of training and knowledge of the presenting signs
      and symptoms of child maltreatment by general practitioners. The need for better
      training is emphasized. Physician engagement in child protection is further
      inhibited by imprecise reporting obligations and an inadequate child protective
      services response by the state. Several randomized, controlled trials of home
      visiting programs by professionals have demonstrated modest effects in the
      primary prevention of child abuse and neglect; however, the prevention of
      recurrent maltreatment of children who remain in the home has proved elusive.
      SUMMARY: Current clinician training in child maltreatment is inadequate. Research
      into effective education of clinicians and program effectiveness is plainly
      needed, and should be supported by increased funding.

PMID- 16601505
TI  - Acute necrotizing pancreatitis in an adolescent with type 2 diabetes.
AB  - PURPOSE OF REVIEW: The demographics of diabetes among adolescents are changing,
      with an increasing prevalence of type 2 diabetes. Since adolescents with type 2
      diabetes are susceptible to the same complications that accompany type 2 diabetes
      in adults, pediatricians are now encountering new diagnosis entities. RECENT
      FINDINGS: A 16-year-old Hispanic male presented to the emergency room with new
      onset diabetes. Laboratory evaluation revealed the diagnosis of hyperglycemic
      hyperosmolar nonketotic state. Within the next 24 hours, the patient's clinical
      status deteriorated with multi organ failure, followed by asystole. At autopsy,
      the pancreas demonstrated acute necrotising pancreatitis. Hyperglycemic
      hyperosmolar nonketotic state is a life-threatening emergency among adults with
      type 2 diabetes, and is now occurring more frequently among adolescents. Acute
      pancreatitis should be considered as a precipitating event, particularly in those
      with severe hypertriglyceridemia. SUMMARY: This case illustrates the changing
      morbidity of diabetes in adolescents and the need to consider acute pancreatitis
      and hyperglycemic hyperosmolar nonketotic in adolescents with severe metabolic
      decompensation. Since hypertriglyceridemia is a known risk factor for acute
      pancreatitis, patients should be monitored, and treated as needed.

PMID- 16601506
TI  - Bibliography. Current world literature. Neonatology and perinatology.

PMID- 16601507
TI  - Translating research into clinical practice: critical interpretation of clinical
      trials in schizophrenia.
AB  - Translating research into clinical practice has in part been hampered by
      practitioners' difficulties in interpreting statistical measures. The main part
      of this article aims to bridge the gap between research and practice by
      describing frequently occurring problems in the methodology and reporting of
      clinical trials. Basic methodological concepts and statistical measures, such as
      different trial designs, randomization, blinding, case numbers, eligibility
      criteria, internal and external validity, efficacy versus effectiveness, the
      meaning of rating scales, choice of comparators, effect size versus P-value and
      the interpretation of risk measures, are explained and their use illustrated. The
      text further presents the outcome from a workshop on 'Translating Clinical
      Studies into Practice' held at an international conference on schizophrenia and
      bipolar disorder in June 2005. The participants suggested more emphasis on
      additional secondary endpoints in clinical trials such as patients' self
      assessments and indicators of well-being. Better training of clinicians in the
      interpretation of scientific results and the use of more meaningful clinical
      outcomes are both needed to effectively translate research into clinical
      practice.

PMID- 16601508
TI  - Metabolic abnormalities associated with second generation antipsychotics: fact or
      fiction? Development of guidelines for screening and monitoring.
AB  - Epidemiological studies have demonstrated a relevant increased risk of diabetes
      in schizophrenic patients who are treated with many atypical antipsychotics,
      irrespective of concomitant weight gain. Numerous case reports and some large
      retrospective cohort studies have documented an increased risk of diabetes with
      some second-generation antipsychotics (SGAs), leading different authors to
      identify patients on SGA as another high-risk group for diabetes in their review
      articles. An American consensus conference dealing with this problem has proposed
      much awaited guidelines for the monitoring of patients on SGA and recommended
      acquiring additional data, especially from large-scale prospective studies. A
      more recent Belgian consensus on the screening and management of antipsychotic
      related metabolic disturbances has proposed a more stringent approach. Here, we
      will cover the current diagnosis of metabolic problems, and provide a review of
      antipsychotic-related metabolic problems (diabetes, lipid abnormalities and the
      metabolic syndrome), as well as guidelines for the screening and management of
      metabolic abnormalities in people treated with antipsychotic medication.

PMID- 16601509
TI  - Schizophrenia: who is at risk? Who is a case?
AB  - It is now almost unanimously acknowledged that schizophrenia is of multifactorial
      origin (i.e. that the clinical expression of the vulnerability induced by genetic
      factors depends on the interactions between this genetic liability and
      environmental risk factors). The list of putative environmental risk factors
      keeps on lengthening, including perinatal events with potential harmful
      neurodevelopmental impact, or later risk factors such as substance use or social
      factors. Although research on genetic and environmental risk factors for
      schizophrenia is of major importance to elucidate the etiology of the disorder,
      the usefulness of this body of knowledge with respect to prevention should be
      considered cautiously. Indeed, there is a huge gap between determining who is at
      increased risk for the disease and predicting who will actually develop
      schizophrenia amongst all subjects at increased risk. How a case of schizophrenia
      is defined is another major issue for etiological research and also for
      prevention. A growing body of evidence suggests the existence of a symptomatic
      continuum between subjects from the general population and subjects with clinical
      psychosis with respect to the occurrence of psychotic experiences. Thus,
      establishing a boundary between psychosis and normality is, by its very essence,
      an arbitrary process. Creating a new diagnostic category of "prodromal psychosis"
      is moving the boundary to include subjects with less severe symptoms. This
      strategy has major clinical implications because the question "who is a case?" is
      often equivalent in clinical practice to the question "who needs treatment?".

PMID- 16601510
TI  - The CNL vision.

PMID- 16601511
TI  - Selecting measures for safety and quality improvement initiatives.

PMID- 16601512
TI  - The HoverMatt system for patient transfer: enhancing productivity, efficiency,
      and safety.

PMID- 16601513
TI  - Helping nurses use NANDA, NOC, and NIC: novice to expert.

PMID- 16601514
TI  - Does patient satisfaction contribute to nursing care quality?
AB  - The use of patient satisfaction tools is routine in healthcare facilities. What
      actually do the results of patient satisfaction surveys tell us about the quality
      of nursing care? The purpose of this article is to provide a discussion about
      patient satisfaction and nursing care. Recommendations are offered about how
      patient satisfaction may be used to improve nursing care and what changes may be
      needed to achieve a high level of patient satisfaction.

PMID- 16601515
TI  - Collaborative strategies to enhance research and evidence-based practice.
AB  - Whether the goal is to generate new knowledge through basic research or to
      effectively use existing knowledge in evidence-based clinical practice,
      collaborative exchange between service and academia is essential. The authors
      describe 2 successful strategies that have been mutually beneficial to a clinical
      agency and a school of nursing in fostering research and evidence-based practice.
      These strategies can be used by other institutions as they strive to meet
      standards for excellence in academia and service.

PMID- 16601516
TI  - Computerized provider order entry: strategies for successful implementation.
AB  - An estimated 522,000 serious medication errors can be eliminated in the United
      States each year through the use of computerized provider order entry. However,
      the implementation of computerized provider order entry is being slowed down by
      resistance from clinicians, particularly physicians. Nurses understand the work
      of physicians and are in a unique position to help overcome their resistance and
      smoothen the transition to computerized provider order entry. The authors outline
      the strategies for nurses to increase organizational acceptance during the
      process of computerized provider order entry implementation.

PMID- 16601517
TI  - Relating outcomes to excellent nursing practice.
AB  - Healthcare professionals must find ways to accelerate the diffusion of knowledge
      within their organizations. Although nurses have extraordinary access to patient
      care data, they may underestimate their roles as data managers and innovators of
      change, and relinquish control of data to others. The authors discuss how nurses
      at an acute psychiatric hospital collect and report their own data to show the
      direct relationship between outcomes and excellence in nursing practice.
      Knowledge that is gained through practice is shared to inspire and sustain needed
      changes.

PMID- 16601518
TI  - Retaining and recruiting mature experienced nurses: a multicomponent
      organizational strategy.
AB  - The aging and impending retirement of the nursing work force will worsen the
      nursing shortage. Because nurses retire for a variety of reasons, retaining older
      nurses or delaying their retirement requires a multifactorial method. The authors
      describe one medical center's multifaceted approach and subsequent strategies to
      create a work environment conducive to retaining the mature, experienced nurse.

PMID- 16601519
TI  - Leadership development: an external-internal coaching partnership.
AB  - Professional coaching is a leadership development strategy that has the potential
      to improve individual and organizational performance, retain leadership talent,
      support succession planning, and help healthcare leaders meet professional and
      personal goals. The authors describe the development and benefits of a
      partnership between an external and an internal coach who joined forces to
      provide individual and group coaching to 64 clinical leaders in a health system.
      Program evaluation demonstrated an excellent return on investment.
      Recommendations for implementing professional coaching programs in other
      healthcare organizations are provided.

PMID- 16601520
TI  - The impact of screening for asymptomatic myocardial ischemia in individuals with
      type 2 diabetes.
AB  - Little is known about factors that contribute to either emotional or behavior
      outcomes following screening for coronary artery disease (CAD). The purpose of
      this prospective study was to explore these outcomes, along with potentially
      contributing factors in individuals enrolled in a screening trial for
      asymptomatic CAD. Included were 47 subjects with type 2 diabetes. Data were
      collected at study baseline and 3 and 6 months following entry by self
      administered questionnaires and telephone follow-up. Emotional outcomes (quality
      of life and anxiety) tended to improve in those who underwent more aggressive
      screening with myocardial perfusion imaging, as well as in those who discussed
      the results of laboratory tests with their providers. Lower levels of diabetes
      competence and higher levels of controlled motivation for diet were associated
      with poorer emotional outcomes. Improvements in CAD risk factor behaviors were
      not observed.

PMID- 16601521
TI  - Caring for octogenarian coronary artery bypass graft patients at home: family
      perspectives.
AB  - Rates of coronary artery bypass graft (CABG) surgery on octogenarians have been
      rising by more than 15% each year since the mid-1980s. Little is known about the
      experience of caring for this select group of patients at home after discharge.
      The purpose of this study was to describe the lived experience of caring for very
      elderly (80 years or older) CABG patients during convalescence at home. Using
      hermeneutic/phenomenological methods, 12 family caregivers were interviewed at
      home during the 4-week postdischarge period. Analysis of data derived from
      interviews revealed that work, personal reaction to caregiving, and experiences
      with formal care were recurrent themes. Caregivers indicated through their
      stories that caring for a recovering octogenarian at home after CABG surgery
      entailed a great deal of work that moderated at about 4 weeks after discharge.
      The caregivers also described varied reactions, both emotional and pragmatic, as
      the weeks unfolded. In addition, the data revealed a range of experiences,
      positive and negative, with healthcare providers and facilities. The study
      findings indicate a need for improvements in the following areas: preoperative,
      postoperative, and discharge education for family members involved in the care of
      the elderly CABG patient, and communication within and between healthcare
      organizations with regard to discharge planning.

PMID- 16601522
TI  - PCNA: Preventive Cardiovascular Nurses Association.

PMID- 16601523
TI  - Constructing and testing a self-help intervention program for high blood pressure
      control in Korean American seniors--a pilot study.
AB  - Although significant progress has been made in the reduction of overall
      cardiovascular risk factors in the United States during the last decade,
      controlling high blood pressure (HBP) remains a difficult task for many
      individuals. In particular, socially disadvantaged groups, such as new
      immigrants, and ethnic minority groups, such as Korean Americans, continue to
      struggle with this chronic disease and suffer unnecessary complications. We
      conducted a quasi-experimental study to test the efficacy of a self-help
      intervention program for HBP control in first-generation Korean American seniors
      with HBP. The intervention consisted of 3 concurrently administered components:
      (1) structured behavioral education on HBP management, (2) home blood pressure
      (BP) monitoring, and (3) monthly support groups facilitated by a bilingual nurse.
      Of the 49 Korean American seniors (> or =60 years old) who agreed to participate,
      31 received the intervention and completed the follow-up interviews at 6 months.
      Final analysis of BP outcomes using repeated measures and postintervention data
      suggested that the self-help intervention was effective in significantly
      improving the proportion of individuals who achieved BP control (<140/90 mm Hg)
      and in lowering both systolic and diastolic BP in the sample. Specifically, the
      BP control rate, which was 29% at baseline, increased at 6 months to 69%.
      Likewise, the mean systolic and diastolic BP values of 142.7 and 87.1 mm Hg at
      baseline decreased to 129.3 and 75.3 mm Hg, respectively, after 6 months of
      follow-up. This improvement of the HBP control rate in the sample highlights the
      clinical efficacy of the self-help intervention for this traditionally
      underserved immigrant group.

PMID- 16601524
TI  - Educational needs of adults with congenital heart disease.
AB  - Adults with congenital heart disease represent a new and growing population of
      patients who pose a challenge to both medicine and nursing. The purpose of this
      study was to identify the educational needs of adults with congenital heart
      disease. The study used a prospective, cross-sectional, case-control study design
      and enrolled 124 adults with congenital heart disease and 124 matched healthy
      controls. Adults with congenital heart disease were more likely to report living
      at home with parents and less likely to be employed compared with healthy
      controls. When those adults with acyanotic and cyanotic congenital heart disease
      were compared, acyanotic adults were twice as likely to be employed.
      Additionally, several areas of educational needs were identified in this study
      for adults with congenital heart disease.

PMID- 16601525
TI  - Psychometric testing of the heart failure somatic awareness scale.
AB  - BACKGROUND: Self-management of heart failure relies on patients to assess their
      symptoms, but their ability to do so is often difficult to determine. The 12-item
      self-report Heart Failure Somatic Awareness Scale (HFSAS) was developed to
      measure awareness of and distress secondary to heart failure symptoms. The
      purpose of this study was to test the psychometric properties of the HFSAS.
      METHODS AND RESULTS: Feasibility and discriminant validity of the HFSAS were
      tested in 49 patients admitted for an exacerbation of heart failure. The HFSAS
      was acceptable to patients and discriminated between heart failure symptoms and
      anxiety (r = 0.25, P = .08). When reliability and validity were tested in 201
      patients with acute heart failure, theta reliability was adequate (0.71). The
      HFSAS was low to moderately correlated with general bodily awareness (r = 0.48).
      No difference was found based on gender, but younger patients had higher mean and
      median HFSAS scores (more distress). The HFSAS was a significant predictor of
      symptom duration prior to seeking care for heart failure; higher scores were
      associated with longer delay before seeking care. CONCLUSION: The HFSAS is
      reliable with content, discriminant, and construct validity. Evaluation of its
      usefulness in teaching patients to monitor daily symptoms is needed.

PMID- 16601526
TI  - Disease knowledge and adherence to treatment in patients with familial
      hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is one of the most common genetic
      metabolic disorders and is associated with a high risk of premature coronary
      heart disease. Primary prevention directed at lifestyle changes, combined with
      preventive medical treatment, is the most important way to reduce the risk of
      coronary heart disease in individuals with FH. Knowledge about the condition and
      adherence to drug treatment may facilitate reaching treatment goals. OBJECTIVE:
      The purpose of this study was to describe disease knowledge and adherence to
      treatment in patients with FH. SUBJECTS AND METHODS: Seventy-four patients, more
      than 18 years of age, with FH were asked to participate. A questionnaire on
      disease knowledge about FH and adherence to drug treatment was sent to the
      patients. Response rate was 92% (n = 68). Drug treatment, laboratory results,
      blood pressure, and smoking were also documented. RESULTS: Most patients knew
      about cholesterol, prevention, and the reason for drug treatment but were less
      informed about the risk of genetic transmission and family history. No
      significant correlation was found between knowledge and low-density lipoprotein
      cholesterol level. A significant, negative correlation between adherence and low
      density lipoprotein cholesterol level was found (r = -.354, P < .01).
      CONCLUSIONS: Patients with FH had scant understanding about the risk of genetic
      transmission and family history. High adherence to drug prescription has
      significant correlation to low-density lipoprotein cholesterol level.

PMID- 16601527
TI  - Nursing care of the patient undergoing coronary artery bypass grafting.
AB  - The role of the professional nurse in the perioperative care of the patient
      undergoing open heart surgery is beneficial for obtaining a positive outcome for
      the patient. This article focuses on the preoperative and postoperative nursing
      care of patients undergoing coronary artery bypass graft surgery. Risk
      assessment, preoperative preparation, current operative techniques, application
      of the nursing process immediately after surgery, and common postoperative
      complications will be explored.

PMID- 16601528
TI  - Q wave versus non-Q wave myocardial infarction: morbidity and mortality patterns
      after cardiac rehabilitation.
AB  - PURPOSE: To document the impact of cardiac rehabilitation on morbidity and
      mortality patterns relative to the type (ie, Q wave vs non-Q wave) of myocardial
      infarction (MI). METHODS: Data (ie, diagnoses, cardiac risk factors, hospital
      readmissions, reinfarctions, comorbidity, and mortality) spanning 5 years from
      the time of initial diagnosis of MI were abstracted from the medical records of
      357 and 163 patients with Q wave and non-Q wave MI, respectively, who
      participated in cardiac rehabilitation. Survival analyses were used to test the
      hypotheses of no difference in time to reinfarction and/or death between persons
      who had a Q wave MI and those who had a non-Q wave MI. RESULTS: Although the
      numbers of reinfarctions (n = 64) and deaths (n = 38) within the sample were
      small and did not allow for statistical significance of findings, trends suggest
      that individuals who had non-Q wave MI had better survival rates for the first 3
      years after cardiac rehabilitation (1.8% vs 4.5%) than did those who had Q wave
      MI. Reinfarction rates, however, were similar for both groups. CONCLUSIONS: The
      small number of deaths and reinfarctions may be indicative of selection biases
      inherent in the current protocols that define the exclusion criteria for
      participation in cardiac rehabilitation. The results of this study call for a
      reevaluation of studies that have touted the efficacy of cardiac rehabilitation
      through the comparison of participating and nonparticipating cohorts. This study
      points to the need for a national database that would allow for a more
      comprehensive quality-controlled data collection that would provide more
      meaningful evaluation of direct and indirect effects of risk variables and
      intervention development.

PMID- 16601529
TI  - Factors influencing food intake in patients with heart failure: a comparison with
      healthy elders.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: Promoting adequate nutritional intake of
      patients with heart failure (HF) is an essential component of comprehensive
      management. This goal can be hampered by decreased appetite, as well as
      psychological, social, and HF-related factors that can affect food intake.
      Factors related to aging may also affect food intake in older patients. The
      purpose of this study was to compare patients with HF to healthy elders regarding
      the extent to which they perceived how appetite and hunger, emotional and social,
      and illness factors affected the amount of food they ate in the previous week.
      SUBJECTS AND METHODS: Sixty-seven patients with HF were recruited from 3
      Midwestern HF clinics. As part of a larger study examining nutrition in HF,
      patients filled out the Food Eating Experiences and Diet (FEED) questionnaire, an
      instrument designed to assess factors affecting appetite and hunger. Patients
      were asked to rate their hunger and appetite on a visual analog scale. On Likert
      type scales, they rated the extent to which appetite/hunger, emotional/social,
      and illness factors affected the amount of food intake. Sixty-eight healthy
      elders were recruited from 2 Midwestern senior citizen centers. As part of a
      study collecting a large data set for comparison with HF patients, healthy elders
      provided demographic and health information and filled out the FEED
      questionnaire. RESULTS AND CONCLUSIONS: Factors rated as affecting food intake
      most often by patients with HF were decreased hunger sensations, diet
      restrictions, fatigue, shortness of breath, nausea, anxiety, and sadness. Factors
      rated most often by healthy elders as affecting food intake were diminished
      hunger sensations, early satiety, eating alone, and decreased senses of taste and
      smell. Among patients with HF, many factors unique from those present due to age
      were reported to affect food intake.

PMID- 16601530
TI  - Do we have what it takes for clinical interventions in practice and research?

PMID- 16601531
TI  - Clinical depression in women after cardiac surgery.
AB  - BACKGROUND AND RESEARCH OBJECTIVE: After coronary artery bypass graft (CABG),
      women are particularly vulnerable to depression because they are more socially
      isolated and are more likely to have preoperative mood disorders than men. The
      purpose of this study was to (1) describe the incidence and course of clinical
      depression in women during the first 6 months after CABG; (2) describe the
      frequency of depressive symptoms after CABG in women; and (3) identify factors
      associated with post-CABG depression in women. SUBJECTS AND METHODS: Before
      hospital discharge, 75 women undergoing CABG for the first time participated in a
      semistructured interview to determine the presence of major or minor depression
      using the Diagnostic and Statistical Manual, Fourth Edition, criteria. In 55
      women, additional interviews were conducted within the first month and at 6
      months after discharge. Data were evaluated using frequencies, analysis of
      variance, Mann-Whitney U test, and logistic regression. RESULTS AND CONCLUSIONS:
      Clinical depression occurred before hospital discharge, in the first month after
      discharge, and 6 months after discharge in 30.9%, 16.4%, and 12.8%, respectively,
      of the women who completed a 6-month follow-up. Younger women, those with more
      perioperative complications, and those with a history of depression were at
      greater risk for clinical depression. After hospital discharge, the occurrence of
      any clinical depression within the first month was associated with an increased
      occurrence of clinical depression 6 months later. Younger women, those with more
      perioperative complications and early depressive symptoms, and those with
      persistent occurrence of the most commonly reported symptoms (anhedonia,
      dysphoria, and fatigue) should be carefully evaluated.

PMID- 16601533
TI  - Factors related to physical activity in Hispanic women.
AB  - Hispanic women are more likely to be sedentary than the general population.
      Increasing physical activity in this at-risk group is an important challenge in
      the prevention and management of coronary heart disease. This article reviews
      research conducted with Hispanic women in whom physical activity was the primary
      focus of study or the primary outcome of interest. Computer and manual searches
      were performed to identify articles published from 1990 to 2005. Factors that
      influence physical activity in Hispanic women include self-efficacy, having a
      concern for own and family health, social support and norms for physical
      activity, serving as a role model to others, and perceived neighborhood
      resources. Despite significant efforts to understand and promote physical
      activity among Hispanic women, much work remains to be done in this area. Future
      research should include attention to cultural, social, and contextual resources
      in understanding and promoting physical activity.

PMID- 16601534
TI  - A behavior change intervention for women in cardiac rehabilitation.
AB  - There is undeniable evidence for physical and psychosocial benefits of cardiac
      rehabilitation programs for individuals suffering from coronary heart disease.
      Yet, fewer women than men are referred to, begin, or complete cardiac
      rehabilitation programs. The numerous logistical, economic, and motivational
      barriers to healthy behavior change place women at risk for subsequent CHD
      events. To close this gender gap and improve outcomes, novel, efficacious, and
      individualized rehabilitative approaches for women with coronary heart disease
      are needed. The purpose of this article is to describe a theory-driven behavioral
      intervention designed exclusively for women with coronary heart disease. The 12
      week intervention is being tested in a randomized controlled trial involving
      women referred to a cardiac rehabilitation program. The tenets of the
      Transtheoretical Model of behavior change and motivational interviewing guided
      the development and implementation of the stage-matched, individualized
      intervention to promote healthy behavior change for women with coronary heart
      disease. The ongoing trial will examine the efficacy of the intervention on
      physiological and psychosocial outcomes.

PMID- 16601535
TI  - Progress in prevention: cardiovascular health for all.

PMID- 16601536
TI  - Alendronate treatment in osteogenesis imperfecta.
AB  - AIMS: Osteogenesis imperfecta (OI) is a chronic, disabling condition
      characterized by bone fragility resulting from defective production of type I
      collagen. Pamidronate therapy is the most extensively studied treatment and has
      proved beneficial. Our objective was to evaluate the effect of alendronate, a
      more potent bisphosphonate than pamidronate, in OI. MATERIALS AND METHODS: Three
      patients (age, 3-7 years; mean, 5 years) (one case, type III; 2 cases, type IV)
      have been given alendronate (0.3-0.56 mg/kg per day orally) for 2 years. Number
      of fractures, ambulation, height growth, and bone mineral density by dual-energy
      x-ray absorptiometry (DXA) were followed up. RESULTS: Bone mineral density
      improved significantly after the 2-year alendronate treatment, which increased by
      47.8% to 106.6% in the lumbar spine and by 24% to 51.4% in forearm bones. The z
      score of lumbar spine DXA values increased from -5.26 +/- 0.84 to -3.1 +/- 0.59.
      The mean of fracture rates did not change significantly. Only one of the patients
      was highly limited in ambulation. She had curved legs and could not sit without
      support before the treatment. She improved to walk with help by the treatment.
      Serum parathormone and alkaline phosphatase concentrations did not change
      significantly. No side effect was detected in clinical and laboratory
      evaluations. CONCLUSION: The study suggests that alendronate is a safe and well
      tolerated drug and that it could increase bone density in children with OI, all
      of which encourage further studies with the bisphosphonates that are more potent
      than pamidronate and can be used orally. In addition, this study is the first
      report using the forearm bone mineral density measurement in OI.

PMID- 16601537
TI  - Paget disease of bone in Colombia and Latin America.
AB  - BACKGROUND: Paget disease of bone has an unknown etiology, having complex
      pathogenesis leading to increased bone resorption in the first phase and an
      excess of bone formation with more advanced disease. The disease has been
      associated to white ancestry in Europe and other countries, being less common in
      people without European origin. OBJECTIVES: The objectives of this study were to
      describe the Colombian cases of Paget disease and search the published literature
      for more Latin American cases and their characteristics. METHODS: Electronic
      databases were searched up to August 2004: MEDLINE, PUBMED, BIREME LILAC, and
      MEDCARIB, evaluating the entire bibliography regarding reports of Paget disease
      in Latin America during the last 30 years. Additionally, we searched the medical
      databases of local reference centers to describe new cases from Colombia.
      RESULTS: We found 14 cases of Paget disease from Colombia; 12 of them were
      previously reported elsewhere and 2 additional cases were found in the medical
      database of a local reference center. We describe the main clinic
      characteristics, including age, symptoms, type and stage of involved bone
      (monostotic or polyostotic), and treatment, which generally are similar to cases
      from Europe or the United States. The literature search showed that a total of
      1149 cases of Paget disease have been previously published from Latin America in
      the last 30 years, more than half of them coming from Argentina and Brazil with
      predominant white ancestry. CONCLUSIONS: We emphasize the presence of white
      European origin or ancestry in the great majority of reported cases of Paget
      disease in Latin America and Colombia. Studies of factors that influence the
      etiology in cases of non-European ancestry would be of interest.

PMID- 16601538
TI  - Serum urate levels and gout flares: analysis from managed care data.
AB  - BACKGROUND: The desired serum urate level (SUA) for prevention of gout attacks is
      widely recommended to be in the subsaturating range, <6.0 mg/dL. OBJECTIVES: The
      objectives of this study were to evaluate attainment of this target SUA among
      gout patients on allopurinol in a naturalistic setting and to assess its impact
      on gout flare risk. METHODS: : This was a retrospective, observational study in a
      southeastern U.S. managed care organization of approximately 2.2 million members.
      The first gout claim/prescription within the intake period (January 1, 2000
      December 31, 2002) was the index date. Included patients had > or =2 visits with
      gout International Classification of Diseases, 9th Revision code (274.xx) or > or
      =1 pharmacy script(s) for allopurinol, colchicine, probenecid, or sulfinpyrazone.
      Excluded patients were <18 years and/or did not have a 1-year continuous
      eligibility pre-/postindex date. Gout flares were defined by office/emergency
      room visit with gout or joint pain code(s) and > or =1 of the following within 7
      days of the visit: intraarticular aspiration/injection, joint fluid microscopy,
      or pharmacy claim for nonsteroidal antiinflammatory drug, colchicine,
      corticosteroid, or ACTH. Multivariable regression analyses were conducted to
      evaluate gout flare risk/rate and association with target SUA. RESULTS:
      Approximately 40% of 5942 gout patients identified used allopurinol postindex.
      Among allopurinol users with pre-/postindex SUA data (n = 162), mean SUA was
      lowered from 8.7 mg/dL to 7.1 mg/dL; reduction was significant (P < 0.001). Among
      allopurinol users who did not have SUA <6.0 mg/dL preindex (n = 147), only 25%
      reached target levels during postindex. Despite pharmacotherapy, patients with
      nontarget levels were 59% more likely to flare than those at target. Allopurinol
      users who were not at target were 75% more likely to flare. CONCLUSION: The
      failure of allopurinol users to achieve target SUA levels of <6.0 mg/dL may be
      attributed to lack of awareness of optimal SUA, allopurinol dosing, compliance,
      and efficacy. Patients who did not achieve target SUA were at increased flare
      risk.

PMID- 16601539
TI  - Risk factors for lack of recent exercise in adults with self-reported,
      professionally diagnosed arthritis.
AB  - BACKGROUND: It is important to identify predictors of exercise/physical activity
      in adults with arthritis. OBJECTIVE: The objective of this study was to estimate
      the association between selected factors and recent exercise/physical activity in
      adults with self-reported, professionally diagnosed arthritis. METHODS: Using
      population-based survey data from the 2004 Behavioral Risk Factor Surveillance
      Survey (BRFSS), we classified respondents according to their arthritis status,
      race, age, general health, education, body mass index, limitations resulting from
      joint symptoms, whether or not they received weight management and/or exercise
      advice from health professionals, and whether or not they engaged in
      exercise/physical activity within the past month. RESULTS: Over one third (34.7%)
      of U.S. adults who completed the BRFSS Arthritis Burden Module reported having
      professionally diagnosed arthritis and 68% of those respondents reported engaging
      in exercise/physical activity within the past month. Respondents who were more
      likely to have engaged in recent exercise/physical activity were men, those with
      higher levels of education, those who were advised by a health professional that
      exercise/physical activity might benefit their arthritis, and those who have
      taken an arthritis education course. Older age, black race, overweight or
      obesity, poorer self-reported general health, and limitations resulting from
      joint symptoms were associated with not engaging in recent exercise/physical
      activity. CONCLUSIONS: Several demographic, behavioral, and disease
      characteristics associate with whether or not adults with arthritis engaged in
      exercise/physical activity during the past month. These should be considered by
      clinicians to appropriately encourage continued activity among physically active
      patients while assessing and addressing barriers to activity for less active
      populations. Findings such as these might also inform efforts to develop targeted
      physical activity interventions to promote increased activity in subgroups that
      tend to be most sedentary.

PMID- 16601540
TI  - Important determinants of bone strength: beyond bone mineral density.
AB  - Osteoporosis is a systemic skeletal disorder characterized by compromised bone
      strength that predisposes individuals to increased fracture risk. Bone strength
      is determined by its material and structural properties. Bone mineral density
      (BMD) is a useful tool for diagnosis; however, this parameter provides
      information regarding only the quantity of mineral in bone, which is only one
      component of bone strength. Osteoporosis treatments have been shown to have
      beneficial effects on bone turnover, microarchitecture, and/or mineralization,
      all of which can help account for the reductions in fracture risk above and
      beyond changes in BMD. Newer noninvasive imaging methods are being developed that
      assess bone strength independent of BMD, and these methods should improve the
      assessment of fracture risk and response to treatment. These imaging methods are
      not currently available for routine clinical use, and therefore, clinicians need
      to continue for now to rely on surrogate markers of bone fragility, including
      BMD, prevalent fracture, and other important risk factors for fracture.

PMID- 16601541
TI  - A rare genetic disorder in the differential diagnosis of the entrapment
      neuropathies: hereditary neuropathy with liability to pressure palsies.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal
      dominant, slowly progressive neuromuscular disorder, which is characterized by
      recurrent acute peripheral nerve palsies. Electrophysiological studies show
      decreased motor and sensory conduction velocities in both clinically affected and
      unaffected nerves. Focal thickening of myelin sheath with sausage-like formation,
      also called tomacula, is seen in nerve biopsies. In genetic studies, 1.5-Mb
      deletion on chromosome 17p11.2 is detected in approximately 85% of HNPP cases and
      point mutations are determined in some cases. We describe a 26-year-old man who
      had a 6-month history of paresthesia in the little fingers of his hands. He was
      diagnosed with HNPP by neurologic examination, and electrophysiological and
      histopathologic studies. Studies in his mother and one brother also showed
      entrapment neuropathy. However, no deletions or point mutations were determined
      in this family. Other genetic defects apart from the known ones might be present
      in this disease. The most frequent entrapment syndrome, carpal tunnel syndrome,
      is also seen in this disease, so physicians dealing with musculoskeletal problems
      should be alert about this subject. Awareness of HNPP may help avoid unnecessary
      operative interventions.

PMID- 16601542
TI  - Anakinra therapy in a child with systemic-onset juvenile rheumatoid arthritis
      after human herpesvirus 6 encephalitis.
AB  - A 3-year-old patient with biopsy-proven herpesvirus 6 (HHV-6) encephalitis
      developed a clinical condition consistent with systemic-onset juvenile idiopathic
      rheumatoid arthritis (SoJIA) and responsive to synthetic interleukin-1 (IL-1)
      receptor therapy. This suggested both a temporal relationship between HHV-6
      infection and the development of SoJIA and the likely involvement of IL-1 in his
      disease. This case adds to the current experience of IL-1 receptor antagonist
      therapy in SoJIA. In addition, it suggests that future prospective studies in new
      onset SoJIA should include an evaluation for HHV-6 infection.

PMID- 16601543
TI  - Relapsing oligoarticular septic arthritis during etanercept treatment of
      rheumatoid arthritis.
AB  - Septic arthritis is a commonly reported complication of rheumatoid arthritis
      (RA). Tumor necrosis factor alpha (TNF-alpha) plays an important role in host
      defense against infection. Inhibition of its activity could therefore be
      anticipated to augment the risk of infection. Both opportunistic and bacterial
      infections have been described in patients with RA treated with anti-TNF-alpha
      therapy. We describe a patient who experienced 2 episodes of septic arthritis.
      Both occurred while the patient was on etanercept. Recurrence developed despite
      prolonged parenteral antibiotic. To our knowledge, this is the first report of
      relapsing oligoarticular methicillin-sensitive Staphylococcus aureus septic
      arthritis despite prolonged antibiotic treatment in a patient receiving
      etanercept therapy. Our case underscores the advisability of discontinuing TNF
      alpha blockade in patients with septic arthritis during prolonged antimicrobial
      therapy.

PMID- 16601544
TI  - An unusual presentation of anti-Jo-1 syndrome, mimicking lung metastases, with
      massive pleural and pericardial effusions.
AB  - We report a case of anti-Jo-1 syndrome (a rare autoimmune condition that may
      manifest with various forms of interstitial lung disease), which in our case
      presented unusually with multiple pulmonary nodules, mimicking carcinoma. She
      subsequently developed pleural and pericardial effusions (which are rare in this
      syndrome), myopathy, and "mechanic's hand," with similar lesions on the feet.
      "Mechanic's foot" noted in this patient has not been previously described. She
      initially responded well to immunosuppression but has subsequently progressed to
      pulmonary fibrosis.

PMID- 16601545
TI  - Febrile myalgia syndrome in familial Mediterranean fever.
AB  - Familial Mediterranean fever is characterized by recurrent polyserositis episodes
      associated with fever. However, the clinical spectrum of this disease has been
      expanded recently and myalgia is now a frequently recognized component.
      Protracted febrile myalgia syndrome was first described in patients with familial
      Mediterranean fever in 1994. This syndrome is characterized by severe paralyzing
      myalgia, high fever, abdominal pain, diarrhea, arthritis/arthralgia, and
      transient vasculitic rashes mimicking Henoch-Schonlein purpura. Recently, we
      evaluated 6 patients with the clinical picture of protracted febrile myalgia
      syndrome in our clinic. One of them was a patient with known familial
      Mediterranean fever, but the others were subsequently diagnosed to have familial
      Mediterranean fever by mutational analyses. Thus, introduction of genetic
      analysis would possibly change the diagnostic criteria for familial Mediterranean
      fever. In addition, all 6 patients presented in the spring months when
      streptococcal infections are at their peak rate and 3 of them had elevated ASO
      levels indicating that streptococci could be one of the agents triggering
      protracted febrile myalgia syndrome.

PMID- 16601546
TI  - Digital clubbing or digital "pseudoclubbing" in systemic sclerosis.

PMID- 16601548
TI  - Basic science for the clinician 37: Protecting against autoimmunity-tolerance:
      mechanisms of negative selection in the thymus.
AB  - As noted in previous articles in this series, tolerance, the ability of the
      immune system to differentiate self from nonself and leave the former alone, is a
      vital characteristic of a successful (and safe) immune system. With the detection
      of the molecule called aire (autoimmune regulator), the mechanism whereby
      autoreactive thymocytes encounter extrathymic proteins within the thymus and
      therefore are deleted, is now far better understood; aire was the subject of a
      prior article in this series. The absence of aire leads to autoimmune
      polyendocrinopathy, proof that aire is the center of an amazing "filtering"
      system. However, there are other mechanisms at work. Irregularities in expression
      of other proteins such as hypoxia-induced factor-1 (HIF-1) and CTLA4, have been
      implicated in autoimmune disease, the former in rheumatoid arthritis, the latter
      in autoimmune thyroid disease and lupus. Defects in intracellular factors
      involved in transcription of key apoptotic proteins have also been implicated in
      the escape of autoreactive thymocytes from the thymus, leading to autoimmune and
      lymphoproliferative syndromes as well. Changes in the proteins that oversee
      acetylation of histone lead to differential patterns of gene expression. At least
      2 proteins involved in this process, HDAC and nur77, have been implicated in
      changes in survival of thymocytes. Yet again, there are multiple layers at work
      in the immune system; I have no idea how many more will be brought to light,
      which are phylogenetically most ancient or which will prove the most clinically
      relevant. For now, it is enough to bask in our new-found knowledge and know that
      the time from laboratory oddity, to animal model development, to therapeutic
      and/or diagnostic applications grows shorter each year since the molecular
      biologic revolution.

PMID- 16601549
TI  - Rising erythrocyte sedimentation rate in a patient with treated polymyalgia
      rheumatica: colon cancer as an accidental association versus paraneoplastic
      syndrome.

PMID- 16601550
TI  - Flexor tendon ruptures in both small fingers of a patient with rheumatoid
      arthritis.

PMID- 16601551
TI  - RACAND syndrome as a paraneoplastic syndrome?

PMID- 16601552
TI  - Acute hip monoarthritis in a patient treated with isotretinoin.

PMID- 16601553
TI  - Inflammatory bowel disease, ankylosing spondylitis, and IgA nephropathy.

PMID- 16601555
TI  - Circadian rhythm of blood pressure and the relation to cardiovascular events.
AB  - Incidences of potentially life-threatening cardiovascular events display a
      diurnal pattern, tending to be higher in the morning than at other times of day.
      The recording of blood pressure at pre-defined intervals under everyday
      circumstances is facilitated by ambulatory blood pressure monitoring (ABPM). This
      technique shows that systolic and diastolic blood pressures display a circadian
      rhythm in most individuals. Typically, at the end of the night on arousal, blood
      pressure surges. This surge coincides with increased cardiovascular events. A
      recent prospective study conducted in Japan, where the incidence of stroke is
      high, provides further evidence for the link between cardiovascular events and
      morning blood pressure surge. Prevalence of both silent ischaemic events and
      multiple cerebrovascular infarcts was highest among the elderly subjects studied,
      with the largest increase in blood pressure on awakening. An increased risk of
      cardiovascular morbidity and mortality is also seen in 'non-dippers' (i.e.
      individuals in whom the normal nocturnal fall in blood pressure is absent or
      blunted). ABPM is superior to clinic blood pressure in predicting cardiovascular
      morbidity and mortality, and this suggests that 24-h blood pressure control may
      be necessary to gain complete benefit from blood pressure-lowering therapy.
      Antihypertensive agents with a long duration of action have the potential to
      provide blood pressure control throughout the dosing interval and thus cover the
      critical early morning period when the blood pressure surges. Clinical studies
      that have compared telmisartan with shorter-acting angiotensin II receptor
      blockers and angiotensin-converting enzyme inhibitors demonstrate that
      telmisartan has a sustained duration of action, with proven efficacy over the
      entire 24-h period between doses, including the critical early morning period.

PMID- 16601556
TI  - Total cardiovascular risk: a new treatment concept.
AB  - Recognition that cardiovascular risk factors, such as hypertension, dyslipidaemia
      and diabetes mellitus, often cluster together has focused attention on the
      concept of total cardiovascular risk. Most current hypertension management
      guidelines emphasize the importance of assessing and managing the total risk in
      an individual patient. Due to the presence of additional risk factors, target
      organ damage and associated clinical conditions, patients may be at high risk of
      cardiovascular events even when their blood pressure is normal or high-normal
      (systolic blood pressure 130-139 mmHg, diastolic blood pressure 80-89 mmHg). Such
      high-risk patients, although common in clinical practice, are often under
      diagnosed. Intensive hypertensive therapy is recommended for high-risk patients.
      In most cases, this will necessitate combination therapy with two or more drugs.
      Moreover, antihypertensive therapy should form one component of a multifactorial
      approach aimed at treating all reversible risk factors. In the future, research
      should be aimed at controlling or reversing subclinical target-organ damage, the
      ultimate aim being to prevent the progression of cardiovascular risk in
      individuals at low or medium risk.

PMID- 16601557
TI  - Early intervention and prevention of myocardial infarction.
AB  - Although there has been a decline in the incidence of ischaemic heart disease in
      Western Europe, North America and Australia/New Zealand, it remains a major cause
      of morbidity and mortality worldwide due to rapidly increasing incidences in
      developing countries. Prevention is key to reducing the burden of this disease.
      The INTERHEART study performed in 52 countries around the world has shown that
      the major risk factors are tobacco smoking, elevated apolipoprotein A,
      hypertension, diabetes mellitus, abdominal obesity, psychosocial factors, low
      fruit and vegetable intake, physical inactivity and alcohol consumption.
      Strategies for prevention by reducing risk factors are applicable universally.
      Individual healthcare providers can implement primary and secondary preventive
      measures to individual patients. Primary prevention involves the avoidance of
      disease in high-risk subjects free of disease, whereas the purpose of secondary
      prevention is to avoid recurrence of myocardial infarction. The general principle
      is to encourage improved and proven lifestyle measures and to prescribe evidence
      based effective medications. Primary prevention requires greater investment and
      planning to identify people at high risk, plus the implementation of life-style
      intervention and pharmacological prevention. In both situations, strategies will
      have to be tailored to suit individual countries and economies. Life-style
      measures (i.e. sensible diet, physical exercise and smoking cessation) are
      effective and need to be promoted. Compliance with preventive measures is
      achievable. Primordial prevention, which involves reducing the prevalence of risk
      factors, rests mainly on public education, media, legislation and government
      policy, and is very dependent on individual governments' commitment and
      determination. It requires promoting a healthier life-style in the population as
      a whole by encouraging people to seek alternatives and making them available.

PMID- 16601558
TI  - Prospects for the prevention of stroke.
AB  - We are currently fighting a battle against a stroke epidemic. Implementation of
      new treatment strategies could save many patients in the future. The control of
      blood pressure is a major objective; however, choosing specific antihypertensive
      therapy (e.g. an agent blocking the renin-angiotensin system) is also important.
      The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study
      demonstrates potential benefits beyond blood pressure reduction of prescribing an
      angiotensin II receptor blocker (ARB) compared with more established therapy in
      patients with left ventricular hypertrophy (LVH). Losartan-based therapy brought
      about regression of LVH and reduced incidences of fatal and non-fatal stroke by
      25%, new-onset diabetes by 25% and atrial fibrillation by 30% more than atenolol
      based therapy for a similar blood pressure control and better tolerability. The
      Study on COgnition and Prognosis in the Elderly (SCOPE) study, although difficult
      to interpret, does not contradict an ARB benefit beyond blood pressure lowering
      in primary prevention linked to targeting the angiotensin type 1 receptor. The
      findings of the MOrbidity and mortality after Stroke, Eprosartan compared with
      nitrendipine in Secondary prevention (MOSES) trial suggest clear-cut ARB benefits
      independent of blood pressure lowering in secondary stroke prevention.
      Experimental findings and other clinical evidence further support the benefits of
      ARBs in stroke prevention. Telmisartan is an ARB with a particularly interesting
      profile for stroke; given the 24-hour efficacy with more pronounced protection
      against the morning blood pressure surge and peroxisome proliferator-activated
      receptor-gamma activity at clinical doses. The unique properties of telmisartan
      for secondary stroke prevention are being tested in the Prevention Regimen For
      Effectively avoiding Second Strokes (PRoFESS) study.

PMID- 16601559
TI  - Endothelial dysfunction: how can one intervene at the beginning of the
      cardiovascular continuum?
AB  - Endothelial dysfunction, characterized by impaired nitric oxide activity,
      constitutes an early step in the pathogenesis of atherosclerotic disease.
      Prospective studies have shown that impaired endothelium-dependent vasorelaxation
      and the vasodilatory response of coronary arteries to acetylcholine predict
      cardiovascular events. Microalbuminuria and estimated glomerular filtration rate,
      which are both deeply influenced by renal nitric oxide activity, are predictors
      of cardiovascular outcome and total mortality but develop at a later stage of
      renal impairment. Endothelial dysfunction reflects early stage renal involvement
      in the atherosclerotic processes. The Telmisartan versus Ramipril in renal
      ENdothelium DYsfunction (TRENDY) trial examined endothelial function of the renal
      vasculature as a therapeutic target in patients with hypertension and type 2
      diabetes, but without albuminuria. The rationale was that blockade of the renin
      angiotensin system (RAS) is cardio- and renoprotective at later stages of the
      disease, but the impact of blockade of the RAS at earlier stages of disease is
      unknown. The results of TRENDY indicate that the endothelial function, as
      assessed by basal nitric oxide activity, can be improved after RAS blockade.
      These data complement the results of the Diabetics Exposed to Telmisartan And
      enalaprIL (DETAIL) trial, which demonstrated that telmisartan and enalapril
      similarly decelerate the progression of overt diabetic nephropathy. The results
      of TRENDY are in accordance with the observed changes in peripheral circulation.
      Endothelium-dependent vasorelaxation could be improved with angiotensin II
      receptor blockers, but not with diuretics or beta-blockers, in hypertensive
      patients. Intervention at the beginning of the renal and cardiovascular continuum
      offers the opportunity to prevent the fatal development towards renal and cardiac
      failure.

PMID- 16601560
TI  - Hypertension treatment and implications of recent cardiovascular outcome trials.
AB  - Clinical trials have shown that effective control of blood pressure reduces the
      risk of cardiovascular events in high-risk patients. For example, data from the
      Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study show
      significant reductions in the incidence of cardiac events, stroke and all-cause
      mortality in patients in whom blood pressure control was achieved compared with
      those in whom blood pressure remained uncontrolled. Although the Antihypertensive
      and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT) demonstrated
      no significant difference in cardiovascular mortality and morbidity between
      patients receiving diuretics, calcium channel blockers or angiotensin-converting
      enzyme (ACE) inhibitors, this finding might have been confounded by differences
      in the blood pressure reductions achieved with the three treatments. Other
      studies have consistently shown that newer antihypertensive agents, such as ACE
      inhibitors and calcium channel blockers, reduce cardiovascular events to a
      similar, or possibly greater, extent as older therapies, such as diuretics and
      beta-blockers. In particular, ACE inhibitors appear to offer additional benefits
      beyond blood pressure reduction in terms of reducing cardiovascular events and
      producing renoprotective effects. Angiotensin II receptor blockers (ARBs) have
      been less extensively studied, but there is evidence already that they have heart
      failure, stroke and renoprotective benefits. The ONgoing Telmisartan Alone and in
      combination with Ramipril Global Endpoint Trial (ONTARGET) is currently comparing
      the effects of the ARB telmisartan 80 mg and the ACE inhibitor ramipril 10 mg,
      alone and in combination, on cardiovascular events in high-risk patients.

PMID- 16601562
TI  - Dual blockade of the renin-angiotensin system with angiotensin-converting enzyme
      inhibitors and angiotensin II receptor blockers in chronic kidney disease.
AB  - Despite the renoprotective effects of angiotensin-converting enzyme inhibitors
      (ACEIs) and angiotensin II receptor blockers (ARBs), many patients with chronic
      kidney disease develop end-stage kidney disease. Combination treatment with an
      ACEI and an ARB is a recently introduced approach to obtain more complete
      blockade of the renin-angiotensin system, based on the different mechanisms of
      action of the two classes of drug. To assess the shortcomings of single treatment
      with ACEIs and ARBs, and the potential benefits of combination treatment, we
      reviewed the experimental and clinical evidence suggesting that combination
      treatment offers more complete blockade of the renin-angiotensin system and
      identified areas in which further research is necessary to confirm the benefits
      of combination treatment. The available data suggest that combination treatment
      with an ACEI and an ARB has a greater renoprotective effect than either drug
      alone. In addition, more recent data have shown that combination treatment is
      more potent in suppressing renal fibrosis, and is well tolerated in patients with
      advanced chronic kidney disease. Clinical trials with rigorous endpoints are
      needed to further establish the benefits of combination treatment in renal
      protection.

PMID- 16601563
TI  - The Study on COgnition and Prognosis in the Elderly (SCOPE)--recent analyses.
AB  - Principal results of the Study on COgnition and Prognosis in the Elderly (SCOPE)
      were published in 2003. Blood pressure reduction was pronounced in both the
      candesartan and control groups, with little difference. With candesartan-based
      treatment, compared with control, the relative risk of non-fatal stroke was 0.72
      (P = 0.04) and of major cardiovascular events 0.89 (P = 0.19). There were no
      significant differences in cognitive outcomes. We have reviewed recent subgroup
      analyses in SCOPE. Cardiovascular endpoints were analysed in patients who did not
      receive add-on treatment after random allocation to groups (post hoc) and in
      patients with certain characteristics at baseline, such as age, sex, diabetes,
      isolated systolic hypertension, or a history of stroke. Cognitive endpoints were
      analysed in patients with baseline Mini Mental State Examination (MMSE) score 24
      28, and in those examined with more extensive investigations than the MMSE. In
      patients without add-on treatment, there were significant risk reductions in the
      candesartan group in major cardiovascular events [relative risk (RR) 0.68, 95%
      confidence interval (CI) 0.51 to 0.92] and mortality (RR 0.73, 95% CI 0.57 to
      0.95). In other subgroups, the relative risks for major cardiovascular events and
      stroke were generally consistent with those in the entire study population.
      However, risk reductions in the candesartan group were particularly marked in
      patients with a history of stroke. In patients with MMSE score 24-28 at baseline,
      the score declined significantly less in the candesartan group (between-group
      difference 0.49, 95% CI 0.02 to 0.97). Cardiovascular outcome benefit of
      candesartan-based treatment was most evident in patients without add-on treatment
      and in those with a history of stroke. Results in other subgroups were generally
      consistent with those in the entire SCOPE study population. In patients with
      slightly low cognitive function at baseline, the MMSE score declined less in the
      candesartan group.

PMID- 16601564
TI  - Angiotensin receptor blockers and cerebral protection in stroke.
AB  - Stroke is a burden of modern civilization, causing death and disability. Nowadays
      it is universally accepted that inhibition of the renin-angiotensin system by
      angiotensin-converting enzyme inhibitors or angiotensin II type 1 (AT1) receptor
      blockers (ARBs) can effectively decrease the incidence of stroke in patients at
      risk. Here, we summarize current knowledge concerning the molecular mechanisms of
      the beneficial effects of inhibition of the renin-angiotensin system in stroke,
      with an emphasis on mechanisms beyond blood pressure reduction; in particular,
      neuroprotection. All major clinical studies comparing the effectiveness of ARBs
      with placebo or other blood pressure decreasing drugs in stroke are mentioned and
      commented on. These clinical data are complemented by data from a selection of
      animal experiments pivotal for the understanding of neuroprotective actions of
      ARBs. Clinical studies have shown that ARBs can be superior to other
      antihypertensive drugs in the prevention of stroke, even if there are no
      differences in blood pressures. Findings from animal experiments suggest that the
      underlying mechanisms include not just inhibition of the detrimental peripheral
      and central actions of angiotensin II mediated by AT1-receptors, but also
      stimulation of unopposed angiotensin II type 2 (AT2) receptors that are
      upregulated in the area of ischaemia. ARBs have been proven to be effective in
      the prevention of stroke via mechanisms that are both dependent on and
      independent of the antihypertensive abilities of the drugs.

PMID- 16601565
TI  - Angiotensin II type 1 receptors in cerebral ischaemia-reperfusion: initiation of
      inflammation.
AB  - Cerebral ischaemia-reperfusion injury is associated with an inflammatory
      response, with contributions from leucocytes and microglia. Formation of free
      radicals and nitric oxide contributes to the development of cerebral infarction
      and of the neurological deficit that follows transient focal ischaemia. The
      circulating and cerebral renin-angiotensin systems contribute, via stimulation of
      the angiotensin II (Ang II) types 1 (AT1) and 2 receptors, to the initiation or
      progression of inflammatory processes, and blockade of AT1-receptors prevents
      irreversible tissue injury and improves outcome from stroke in animal
      experiments. Such cerebral protection can be achieved even when treatment is
      initiated hours after established reperfusion. Blockade of AT1-receptors also
      reduces the incidence of stroke and cardiovascular mortality associated with
      stroke in patients; however, the mechanisms underlying the prevention of stroke
      by AT1-receptor blockade in patients remain to be elucidated. In this review we
      summarize the existing experimental and clinical data demonstrating that the
      renin-angiotensin system contributes to the inflammation and subsequent
      irreversible injury after cerebral ischaemia-reperfusion. We conclude that AT1
      receptor blockade reduces cerebral ischaemia-reperfusion injury in part by
      attenuating inflammatory processes.

PMID- 16601566
TI  - Angiotensin II: multitasking in the brain.
AB  - In addition to controlling systemic blood pressure, angiotensin II (Ang II) has
      several roles in the brain, including the regulation of cerebrovascular flow and
      the reaction to stress. In order to clarify the central effects of Ang II and its
      type 1 (AT1) receptors, we reviewed the literature reporting recent research on
      the effects of pretreatment with the AT1-receptor blocker, candesartan, on
      experimental ischemia, cerebrovascular remodeling, and inflammation in
      spontaneously hypertensive rats (SHRs), and the responses to stress induced by
      isolation and by cold-restraint. Angiotensin II regulates the brain circulation
      through stimulation of AT1-receptors located in the cerebrovascular endothelium
      and central pathways. SHRs express greater numbers of endothelial AT1-receptors
      and a central sympathetic overdrive, resulting in pathological cerebrovascular
      growth, inflammation, decreased cerebrovascular compliance, and enhanced
      vulnerability to brain ischemia. Sustained central AT1-receptor antagonism
      reverses these effects. Sustained reduction of AT1-receptor stimulation before
      stress prevents the hormonal and sympathoadrenal stress responses during
      isolation and prevents the gastric ulceration stress response to cold-restraint,
      indicating that increased AT1-receptor stimulation is essential to enhance the
      central sympathetic response and the formation and release of corticotropin
      releasing factor (CRF) and arginine vasopressin that occur during stress. AT1
      receptor blocking agents reverse the cortical alterations in CRF1 and
      benzodiazepine receptors characteristic of isolation stress, effects probably
      related to their anti-anxiety effect in rodents. Sustained reduction of Ang II
      tone by AT1-receptor antagonism could be considered as a preventive and
      therapeutic approach for brain ischemia and stress-related and mood disorders.
      Additional preclinical studies and controlled clinical trials are necessary to
      confirm the efficacy of this novel therapeutic approach.

PMID- 16601567
TI  - Involvement of the renin-angiotensin system in migraine.
AB  - Migraine is a common episodic headache that predominantly affects young adults,
      particularly women in their most productive years. Many of the prophylactic
      agents available today have side-effects that are not compatible with long-term
      use. The discovery that drugs influencing the renin-angiotensin system (RAS),
      which have few side-effects, were effective in some patients with migraine led to
      several studies investigating a possible link between the angiotensin system and
      migraine pathophysiology. Clinical trials indicated that angiotensin-converting
      enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are
      effective in the prophylactic treatment of migraine. These findings are further
      supported by pharmacoepidemiological, genetic, and physiological studies. In
      addition, it is known that the RAS has neurophysiological, chemical, and
      immunological effects that are of relevance in migraine pathophysiology. On the
      basis of evidence presented in this review, we find it likely that the RAS has a
      clinically important role in migraine pathophysiology. The effect of ARBs and
      ACEIs on migraine is probably not attributable to their effect on blood pressure.
      The RAS has several actions that may be relevant in migraine pathophysiology, but
      the reason for the prophylactic effect of ARBs/ACEIs in migraine remains a matter
      of speculation.

PMID- 16601568
TI  - Pathophysiological regulation of the AT1-receptor and implications for vascular
      disease.
AB  - BACKGROUND: Numerous studies have demonstrated that activation of the angiotensin
      II type 1 (AT1) receptor plays an important role in the pathogenesis of
      cardiovascular diseases. RESULTS: AT1-receptor activation by angiotensin II is
      not only involved in the regulation of blood pressure, water and sodium
      homeostasis, and control of other neurohumoral systems, but also leads to
      excessive production of reactive oxygen species and to hypertrophy,
      proliferation, migration, and apoptosis of vascular cells. AT1-receptor-induced
      oxidative stress may cause nitric oxide inactivation, lipid oxidation, and
      activation of redox-sensitive genes, such as chemotaxis and adhesion molecules,
      pro-inflammatory cytokines, and matrix metalloproteinases, all of which are
      involved in the initiation and progression of endothelial dysfunction and
      manifested atherosclerosis. The expression levels of the AT1-receptor define the
      biological efficacy of angiotensin II. Many agonists, such as, for example,
      angiotensin II, growth factors, low-density lipoprotein cholesterol, insulin,
      glucose, estrogen, progesterone, reactive oxygen species, cytokines, nitric
      oxide, and many others, are known to regulate AT1-receptor expression in vascular
      cells. The pathophysiological relevance of dysregulated AT1-receptor expression
      has been demonstrated in many cell culture and animal studies and interventional
      trials in humans. Hypercholesterolemia, estrogen deficiency, and diabetes
      mellitus are associated with enhanced vascular AT1-receptor expression, increased
      oxidative stress, and endothelial dysfunction. Importantly, treatment with AT1
      receptor blockers may inhibit the onset and progression of vascular oxidative
      stress and inflammation, endothelial dysfunction, atherosclerosis, and related
      organ damage. CONCLUSION: Inhibition of AT1-receptor activation is presumably a
      primary treatment goal in patients suffering from cardiovascular risk factors or
      manifested atherosclerotic diseases.

PMID- 16601569
TI  - Long-lasting angiotensin type 1 receptor binding and protection by candesartan:
      comparison with other biphenyl-tetrazole sartans.
AB  - BACKGROUND: The ability of biphenyl-tetrazole angiotensin type 1 (AT1) receptor
      antagonists (BTsartans) to block angiotensin II (Ang II)-mediated responses has
      been extensively investigated in vascular tissues and, more recently, in cell
      lines expressing the human AT1-receptor. When pre-incubated, BTsartans acted
      surmountably (shifting the Ang II concentration-response curve to the right) or
      insurmountably (also decreasing the maximal response). It was shown that their
      insurmountable behaviour is due to the formation of tight, long-lasting complexes
      with the receptor. Partial insurmountable antagonism is due to the co-existence
      of tight and loose complexes. The proportion of insurmountable antagonism, the
      potency and the dissociation rate of the BTsartans decreases in the order:
      candesartan > EXP3174 (losartan's active metabolite) > valsartan > irbesartan >>
      losartan. OBJECTIVE: It is of interest to explore how tight AT1-receptor binding
      of BTsartans such as candesartan might contribute to their long-lasting clinical
      effect. METHODS: Computer-assisted simulations (COPASI program) were performed to
      follow the receptor-occupation and protection by different antagonists as a
      function of time. Free antagonist concentrations were allowed to decrease
      exponentially with time. RESULTS: The simulations suggest that slow dissociation
      does not tangibly prolong receptor occupancy if the free antagonist is eliminated
      at a slower pace (as is the case for BTsartans). Yet when surmountable and
      insurmountable antagonists occupy the same amount of receptors, insurmountable
      antagonists offer appreciably better protection against fluctuations in natural
      messenger concentration. CONCLUSION: Slow receptor dissociation and slow
      antagonist elimination are likely to act in synergy to produce long-lasting
      receptor protection.

PMID- 16601570
TI  - Angiotensin receptor blockade with candesartan in heart failure: findings from
      the Candesartan in Heart failure--assessment of reduction in mortality and
      morbidity (CHARM) programme.
AB  - BACKGROUND: Randomized clinical trials in patients with chronic heart failure and
      reduced left ventricular ejection fraction (LVEF) have demonstrated the life
      saving and symptomatic benefits of angiotensin-converting enzyme (ACE)
      inhibitors, beta-blockers, and, in more selected patients, spironolactone.
      Despite these major advancements, the prevalence of heart failure continues to
      increase mainly as a consequence of aging populations. The development of
      angiotensin II type 1 receptor blockers (ARBs) provides a pharmacologically
      distinct mechanism of inhibiting the renin-angiotensin-aldosterone system. ARBs
      offer the potential to produce further clinical improvements for patients with
      heart failure above and beyond ACE inhibitors, as well as an alternative for
      those intolerant to an ACE inhibitor. METHODS: The Candesartan in Heart failure-
      Assessment of Reduction in Mortality and morbidity (CHARM) programme was designed
      as three parallel, randomized, double-blind, placebo-controlled clinical trials
      comparing candesartan with placebo in three different but complementary
      populations of patients with symptomatic heart failure. RESULTS: In patients with
      intolerance to an ACE inhibitor and an LVEF of 40% or less (the CHARM-Alternative
      trial), candesartan reduced cardiovascular mortality and hospitalizations for
      heart failure by 23% (P < 0.001). In patients with an LVEF of 40% or less treated
      with an ACE inhibitor (the CHARM-Added trial), candesartan reduced cardiovascular
      death and hospitalization for chronic heart failure by 15% (P = 0.011). In
      patients with a LVEF greater than 40% (the CHARM-Preserved trial),
      hospitalizations for heart failure and new-onset diabetes were significantly
      reduced. CONCLUSION: The CHARM programme, together with evidence from mechanistic
      studies and from other large trials with ARBs, constitutes a firm basis for
      including an ARB in the therapeutic arsenal in the treatment for chronic heart
      failure.

PMID- 16601571
TI  - Vascular and metabolic effects of candesartan: insights from therapeutic
      interventions.
AB  - BACKGROUND: Effects of angiotensin II type 1 receptor blockers (ARBs) to improve
      endothelial dysfunction may be due to mechanisms in addition to the reduction of
      high blood pressure per se. Endothelial dysfunction is characterized by vascular
      inflammation that contributes to clinically significant atherosclerosis and by an
      increased tendency for thrombus formation. Hypertensive patients have impaired
      endothelial functions that have positive predictive power with respect to future
      cardiovascular events. OBJECTIVES: The present review will focus on multiple
      mechanisms underlying vascular and metabolic effects of ARBs that may synergize
      to prevent or regress atherosclerosis, onset of diabetes, and coronary heart
      disease. CONCLUSIONS: Angiotensin II accelerates the development of
      atherosclerosis by activating angiotensin II type 1 receptors that then promote
      superoxide anion generation and oxidative stress, leading to activation of
      nuclear transcription factor and endothelial dysfunction. Activation of
      angiotensin II type 1 receptors also stimulates increased expression of
      plasminogen activator inhibitor type 1 and tissue factor. Endothelial dysfunction
      associated with the metabolic syndrome and other insulin-resistant states is
      characterized by impaired insulin-stimulated production of nitric oxide from the
      endothelium and decreased blood flow to skeletal muscle. Increasing insulin
      sensitivity therefore improves endothelial function, and this may be an
      additional mechanism whereby ARBs decrease the incidence of coronary heart
      disease and the onset of diabetes. Adiponectin serves to link obesity with
      insulin resistance. In addition, adiponectin has anti-atherogenic properties.

PMID- 16601572
TI  - Effect of angiotensin II type 1 receptor antagonism on endothelial function: role
      of bradykinin and nitric oxide.
AB  - BACKGROUND: The important role of the endothelium for regulation of vascular
      tone, growth, inflammatory response, coagulation and thrombocyte adhesion has now
      been recognized. Endothelial function has largely been assessed as endothelium
      dependent vasodilation, assuming that endothelium-dependent vasomotion represents
      a surrogate marker for other important endothelial functions. An important
      rational for this approach has been the observation that both endothelium
      dependent vasomotion and other protective endothelial functions are at least
      partially mediated by nitric oxide. Accumulating clinical studies have now
      demonstrated a close and independent association of impaired endothelium
      dependent vasodilation with cardiovascular events and prognosis. These findings
      have stimulated interest in treatment options to improve endothelial function in
      patients at high cardiovascular risk. DISCUSSION: This article describes recent
      insights into endothelial effects of both angiotensin-converting enzyme (ACE)
      inhibition and angiotensin II type 1 (AT1) receptor blockade, which have both
      been shown to improve endothelial function (i.e. by increasing endothelial nitric
      oxide availability via bradykinin-dependent endothelial nitric oxide release).
      ACE has a high affinity for bradykinin and degrades the peptide, so ACE
      inhibition may increase bradykinin-dependent effects by preventing bradykinin
      degradation. Interestingly, AT1-receptor blockade appears to stimulate the
      bradykinin-nitric oxide pathway by increased angiotensin II type 2 receptor
      activation. Moreover, both treatment strategies prevent increased inactivation of
      endothelial nitric oxide by oxygen radicals, by reducing AT1-receptor-dependent
      activation of the oxidant enzyme NADPH oxidase and increasing the activity of the
      vascular antioxidant enzyme extracellular superoxide dismutase. These beneficial
      effects of ACE inhibition and AT1-receptor blockade are likely to contribute to
      their effects on cardiovascular events.

PMID- 16601573
TI  - Interaction between nitric oxide and angiotensin II in the endothelium: role in
      atherosclerosis and hypertension.
AB  - BACKGROUND: Although there is overwhelming evidence that hypertension promotes
      atherosclerosis, the relative contribution and/or interaction of vasoactive and
      hemodynamic factors remain undefined. Endothelial dysfunction complicates
      hypertension and is a precursor of atherosclerosis. It is characterized by a
      reduction in the bioavailability of vasodilators, particularly nitric oxide, and
      an increase in the activity of vasoconstrictors, including angiotensin (Ang) II
      and reactive oxygen species (ROS). Nitric oxide antagonizes the vasoconstrictive
      and pro-atherosclerotic effects of Ang II, whereas Ang II decreases nitric oxide
      bioavailability by promoting oxidative stress. OBJECTIVES: The present review
      will focus on the interaction among nitric oxide, Ang II, and ROS in the
      endothelium and will examine their role in vascular tone and atherogenesis. In
      this context, studies from our laboratory will be reviewed demonstrating that
      salt-sensitive hypertension is a vascular diathesis characterized by a local
      activation of Ang II and NAD(P)H oxidase-derived ROS in the setting of
      insufficient nitric oxide. In hypertensive Dahl salt-sensitive rats, a paradigm
      of human salt-sensitive hypertension, inhibition of Ang II type 1 receptor or
      NAD(P)H oxidase-derived ROS prevented the development of endothelial dysfunction,
      upregulation of pro-atherogenic molecules, and vascular ROS generation,
      independently of blood pressure. CONCLUSIONS: Salt sensitivity, an independent
      risk factor for increased cardiovascular morbidity and mortality, affects
      approximately 50% of hypertensives. Our studies suggest that, in salt-sensitive
      hypertension, atherogenesis is more closely linked to oxidative stress than to
      the hemodynamic stress of hypertension. To prevent or arrest atherosclerosis,
      antihypertensive therapy should aim at restoring the homeostatic balance between
      vasoactive factors in the vascular wall.

PMID- 16601574
TI  - Angiotensin-sympathetic system interactions in cardiovascular and metabolic
      disease.
AB  - BACKGROUND: Blood pressure, as well as blood volume homeostasis, depends to a
      large extent on humoral influences stemming from the renin-angiotensin axis and
      the sympathetic nervous system. Evidence has been provided that a large part of
      this homeostatic modulation is effected by the complex interactions between the
      two systems. OBJECTIVES: The present review will focus on three major issues.
      First it will examine the physiological and pathophysiological relevance of
      angiotensin-sympathetic crosstalk discussing possible sites, mechanisms and
      effects of the interaction. It will then address the clinical relevance of these
      inter-relationships by reviewing data collected in cardiovascular and non
      cardiovascular diseases. Finally, the influences of angiotensin II on adrenergic
      function will be examined as possible targets of cardiovascular drug treatment.
      CONCLUSIONS: By interrupting the influences of angiotensin II on sympathetic
      function, therapeutic interventions aimed at blocking the renin-angiotensin
      system exert favourable effects on the haemodynamic, metabolic and renal profile.
      This has important implications for the treatment of hypertension, congestive
      heart failure, renal insufficiency and metabolic syndrome.

PMID- 16601575
TI  - Preventing diabetes in patients with hypertension: one more reason to block the
      renin-angiotensin system.
AB  - Patients with essential hypertension are at increased risk of type 2 (non-insulin
      dependent) diabetes. Recent large studies have been unable to delineate any
      superiority in one class of antihypertensive drug over another, independent of
      their effects in reducing blood pressure; however, in the longer term,
      antihypertensive agents that are able to reduce the risk of diabetes may have a
      theoretical advantage. To this end, the findings of several recent clinical
      trials have suggested that blockade of the renin-angiotensin system (RAS) may
      protect against the development of de-novo diabetes in 'at risk' patients. This
      beneficial effect appears to outweigh both the adverse metabolic effects of
      agents used in the control arm of these studies and the control of blood pressure
      achieved. Furthermore, recent evidence suggests that the RAS may have a direct
      role in the pathogenesis of diabetes. Angiotensin-mediated increases in oxidative
      stress, inflammation, and free fatty acids concentrations potentially contribute
      to beta-cell dysfunction in diabetes. In addition, activation of the RAS appears
      to potentiate the action of other pathogenic pathways, including glucotoxicity,
      lipotoxicity, and advanced glycation. In experimental models of type 2 diabetes,
      blockade of the RAS with angiotensin-converting enzyme inhibitors or angiotensin
      receptor antagonists also results in the improvement of islet structure and
      function. At least three large controlled trials are currently under way to study
      the utility of blockade of the RAS in the development of diabetes, including
      studies of combination therapy. It is hoped that these studies will demonstrate
      the true potential of blockade of the RAS for the prevention of diabetes.

PMID- 16601576
TI  - Cost implications of development of diabetes in the ALPINE study.
AB  - OBJECTIVE: To present a cost-effectiveness analysis of the Antihypertensive
      Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation study
      (ALPINE). DESIGN: In newly diagnosed hypertensive individuals as yet untreated
      with drugs, the ALPINE study compared the 1-year metabolic effects of inexpensive
      treatment with a diuretic (hydrochlorothiazide), alone or in combination (84%)
      with a beta-adrenoceptor blocker (atenolol), with that of newer but also more
      expensive antihypertensive treatment with an angiotensin II receptor blocker
      (candesartan), alone or in combination (71%) with a calcium antagonist
      (felodipine). No crossover of medication was allowed. The cost-effectiveness
      analysis included costs for antihypertensive treatment during follow-up, and
      lifetime costs for care of diabetes mellitus diagnosed during follow-up. Cost per
      patient was calculated using Swedish prices and costs, translated into US dollars
      (US$), at 2004 prices. RESULTS: Diabetes mellitus was diagnosed in nine patients
      during the 1-year follow-up period of the study, eight in the hydrochlorothiazide
      group (4.1%) and one (0.5%) in the candesartan/felodipine group (P < 0.05). The
      cost of antihypertensive treatment per patient was US$92 in the
      hydrochlorothiazide/atenolol group and US$422 in the candesartan/felodipine
      group. Lifetime cost for care of diabetes mellitus per patient in the two groups
      was US$1013 and US$127, respectively. Total cost per patient was US$556 less in
      the candesartan/felodipine group. In sensitivity analyses, the outcome for the
      candesartan/felodipine group ranged from cost savings to an incremental cost of
      US$30 000 per case of diabetes mellitus prevented. In all analyses but one, the
      additional cost for antihypertensive treatment in the candesartan/felodipine
      group could be balanced by the reduced lifetime cost for care of diabetes
      mellitus. CONCLUSIONS: The results suggest that an antihypertensive treatment
      strategy with candesartan and felodipine may have a favourable health economic
      impact in the longer term.

PMID- 16601577
TI  - Role of the angiotensin II type 1 receptor in the pathogenesis of diabetic
      retinopathy: effects of blood pressure control and beyond.
AB  - Diabetic retinopathy is characterized by both functional and morphological
      changes in the retinal microvessels that can lead to macular edema,
      neovascularization, and vision loss. Hypertension has been identified as a major
      risk factor for diabetic retinopathy and randomized clinical trials have shown
      that reduction of blood pressure using angiotensin converting enzyme (ACE)
      inhibitors reduces the progression of diabetic retinopathy. The major components
      of the renin-angiotensin system have been identified in ocular tissues.
      Activation of angiotensin II type 1 (AT1) receptors expressed on retinal
      endothelial cells and pericytes has been implicated in contributing to the
      microvascular abnormalities in diabetic retinopathy. We have examined the
      experimental and clinical evidence for the role of the renin-angiotensin system
      in the pathogenesis of diabetic retinopathy, including the effects of ACE
      inhibition and AT1-receptor antagonism on diabetes-induced abnormalities in
      retinal hemodynamics, vascular permeability, and leukostasis; retinal
      neovascularization in rodent models of oxygen-induced retinopathy; and results
      from randomized clinical trials that have investigated the effects of ACE
      inhibitors on the progression of diabetic retinopathy in diabetic patients in the
      absence or presence of hypertension. The effects of AT1-receptor antagonism on
      the retina have been attributed to decreases in systemic blood pressure and the
      concomitant reduction in mechanical vascular stretch, in addition to the
      intraocular effects blocking AT1-receptor stimulation of retinal endothelial
      cells and pericytes. Results from the current DIabetic REtinopathy Candesartan
      Trials program will evaluate the potential of the AT1-receptor as a therapeutic
      target for diabetic retinopathy.

PMID- 16601578
TI  - Diabetes, nephropathy, and the renin system.
AB  - Blockade of the renin-angiotensin system has become crucial in the management of
      type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus,
      especially in patients who are at risk of nephropathy. In this review, we address
      the issue of why the renin system and its blockade are so important. As in many
      complex processes, diabetic nephropathy reflects an interaction between genetic
      factors and environmental factors. Recent research has uncovered a number of
      environmental factors; control of these factors should contribute to improved
      management. The renin system is important in patients with diabetes mellitus
      because so many relevant factors converge on the intrarenal renin system.

PMID- 16601579
TI  - Effects of selective angiotensin II and beta1-receptor blockade on renal
      haemodynamics and sodium handling during orthostatic stress in healthy
      individuals.
AB  - BACKGROUND: Lower-body negative pressure (LBNP) induces a progressive activation
      of neurohormonal systems and a renal tubular and haemodynamic response that
      mimics the renal adaptation observed in congestive heart failure. Both
      angiotensin II receptor blockers and beta-blockers have been shown to reduce
      morbidity and mortality in patients with congestive heart failure. OBJECTIVE: To
      investigate whether part of the beneficial effects of angiotensin II receptor
      blockers and beta-blockers in congestive heart failure is mediated through an
      improvement in renal haemodynamics and sodium excretory capacity. METHODS AND
      RESULTS: The study was performed in healthy normotensive individuals exposed to
      three levels of LBNP and treated with placebo, 200 mg metoprolol once daily, or
      16 mg candesartan once daily, for 10 days. Our results show that candesartan
      increased renal blood flow, and thereby blunted the vasoconstriction induced by
      LBNP. This effect was not found with metoprolol. More importantly, both
      metoprolol and candesartan prevented the sodium retention induced by LBNP, but
      only candesartan promoted sodium excretion during the 2-h recovery period--that
      is, once LBNP was interrupted. CONCLUSIONS: These results suggest that blockade
      of the renin-angiotensin and sympathetic nervous systems in heart failure may be
      beneficial in part as a result of improved sodium excretion.

PMID- 16601580
TI  - Initial data supporting the design of the Candesartan in Heart failure-
      assessment of reduction in mortality and morbidity (CHARM) programme.
AB  - BACKGROUND: The therapies developed to treat heart failure over the years have
      resulted in a significant improvement in clinical outcome. The 1-year mortality
      following hospital discharge remains unacceptably high, however. Furthermore, a
      significant number of patients are unable to tolerate angiotensin-converting
      enzyme (ACE) inhibitors. Clearly, scope remains for the improvement of
      neurohormonal blockade in patients with heart failure, and there is a particular
      need for alternative therapies in patients who are unable to tolerate ACE
      inhibitors. The use of angiotensin II receptor blockers may provide a means of
      fulfilling these needs. OBJECTIVES: This paper reviews the studies examining the
      angiotensin II receptor blocker candesartan in comparison with placebo, in
      comparison with ACE inhibitors, and in combination with ACE inhibitors.
      CONCLUSIONS: Overall the review found candesartan was effective and safe in
      various clinical settings. These initial data were used to design the Candesartan
      in Heart failure--Assessment of Reduction in Mortality and morbidity (CHARM)
      programme. The mechanistic studies performed prior to the CHARM programme
      supported the rationale to design a large trial examining the effects of
      candesartan on clinical events.

PMID- 16601581
TI  - Long-term safety of high-dose angiotensin receptor blocker therapy in
      hypertensive patients with chronic kidney disease.
AB  - BACKGROUND: Reducing urinary protein excretion in patients with renal disease is
      an important therapeutic target to prevent the progression of renal and
      cardiovascular disease. Drugs such as angiotensin-converting enzyme inhibitors
      and angiotensin receptor blockers (ARBs), which block the actions of the renin
      angiotensin-aldosterone system, are recommended because they reduce blood
      pressure and proteinuria. Recently, the use of higher doses of ARBs, up to three
      times the maximal approved dose, resulted in further reductions in protein
      excretion. Despite the effectiveness of this therapeutic approach, no long-term
      safety analysis has been conducted in patients receiving high-dose ARB treatment.
      OBJECTIVE: To study the long-term safety of high-dose ARB treatment. METHODS: We
      observed 48 patients [44 men and 4 women; ages 64 +/- 15 years (mean +/- SD),
      weight 88 +/- 28 kg, estimated glomerular filtration rate 53 +/- 23 ml/min]
      receiving treatment with high doses (1.5-5 times greater than the maximum
      approved dose) of ARBs, for 40 +/- 24 months (range 6-98 months). RESULTS: The
      average ARB dose tended to increase over time and was 3.2 +/- 1.2 times greater
      at the end of the study than that at the start. Systolic blood pressure was
      similar at the beginning and end of the study period (132 +/- 20 and 125 +/- 20
      mmHg, respectively), but diastolic blood pressure showed a decrease throughout
      the study and was significantly reduced (P < 0.05) in association with 1.5x and
      2x the maximum ARB dose (73 +/- 11 and 72 +/- 10 mmHg, respectively) when
      compared with baseline (78 +/- 11 mm Hg). There was a trend (P > 0.05) for
      increases in concentrations of serum potassium (0.2 +/- 0.9 mmol/l) and
      creatinine (0.3 +/- 0.7 mg/dl) with increases in dose from baseline to the end of
      the study. Serum creatinine concentration was greater (P < 0.05) at the periods
      of 3x and 4x the maximum dose, but this represented increases of only 12 and 20%
      from baseline, respectively. CONCLUSIONS: High-dose ARB treatment in patients
      with chronic renal disease is not associated with any clinically significant long
      term negative effects on serum creatinine or potassium and is thus a important
      therapeutic modality with which to achieve further reductions in urinary protein
      excretion.

PMID- 16601582
TI  - Current treatments of primary aneurysmal bone cysts.
AB  - The management of aneurysmal bone cyst depends on the age of the patient, the
      location, extent, aggressiveness and the size of the lesion. In the light of
      their experience and a review of the literature of 1256 aneurysmal bone cysts,
      the authors analyzed various treatment modalities. Inactive lesions can heal with
      biopsy or curettage alone. In active or aggressive lesions, elective treatment
      usually consists of curettage, whether associated or not with bone grafting and
      local adjuvants. Aneurysmal bone cyst in young children do not seem more
      aggressive than in older children. In pelvic locations, the emergence of a few
      cases of spontaneous healing (even in active or aggressive lesions) encourages
      the adoption of clinical and radiological supervision for some months after
      biopsy when possible. In some cases, the localization and extent of the cyst are
      such that operative treatment is extremely hazardous. Selective arterial
      embolization has made a considerable contribution towards the therapeutic
      solution of such cases. For some authors, direct percutaneous Ethibloc injection
      can be recommended as the first-choice treatment except in spinal lesions.
      Nevertheless, the complications encountered in some series after percutaneous
      embolization of aneurysmal bone cyst with Ethibloc should encourage the use of
      Ethibloc injection not as an initial treatment but as a reliable alternative to
      surgery.

PMID- 16601583
TI  - Postural control in patients with severe idiopathic scoliosis: a prospective
      study.
AB  - Thirty-one patients with severe adolescent idiopathic scoliosis were evaluated
      preoperatively by computerized dynamic posturography. Curve type, magnitude and
      spine balance were measured radiographically. In four girls, a very mild
      vestibular dysfunction was observed on the sensory organization analysis, and
      three of them had a horizontal shift of more than 2 cm; a disbalance was observed
      in only three other patients among the 27 patients with normal posturography.
      These results suggest that abnormalities in the sensory systems are not involved
      in the etiology of severe adolescent idiopathic scoliosis. The vestibular
      dysfunction detected in the four patients was most probably the result of
      disbalance and not the cause of the disease.

PMID- 16601584
TI  - Assessment of the correlation between commonly used radiographic parameters in
      normal, subluxated and dislocated hips.
AB  - The correlations between the commonly used radiographic parameters, center-edge
      angle (CEA), acetabular-head index (AHI), acetabular index angle (AIA),
      acetabular angle (AA) and ACM angle, in normal, subluxated and dislocated hips
      were investigated in the radiographs of 364 normal, 23 subluxated and 19
      dislocated hips of patients between 5 and 18 years of age. A significant
      correlation was observed between all the parameters in normal hips. A significant
      correlation between AIA and the other four parameters, and between CEA-AHI and AA
      ACM, was noted in subluxated hips. AIA-AA and AIA-ACM had significant
      correlations in dislocated hips. It was concluded that measurement of more than
      one radiographic parameter might be better to exactly evaluate the radiographic
      hip anatomy in developmental dysplasia of the hip.

PMID- 16601585
TI  - Lateral growth disturbance of the proximal femur in premature infants who had
      neonatal sepsis.
AB  - This is a retrospective review of four patients in whom a pattern of growth
      disturbance of the proximal femur with the bony bridge developed. They were born
      prematurely with low birth weight at birth and they had a suspicious sepsis, but
      they did not have any signs of localized infection. All presented with a
      progressive gait disturbance and a leg-length discrepancy. Radiographs showed an
      anterior tilting of the capital femoral epiphysis. Computed tomography and
      magnetic resonance imaging showed partial physeal closure with bony bridges. This
      case series suggests an association between neonatal sepsis of prematurity and
      growth disturbance of the proximal femur.

PMID- 16601586
TI  - Hip abductor function in adults treated for Perthes disease.
AB  - This study investigated hip abductor function by isokinetic dynamometry and gait
      analysis in adults treated for Perthes disease and its relationship with clinical
      results. Eighteen patients were divided into two groups on the basis of good
      versus poor clinical results (IOWA hip-rating scale above or below 90 points). We
      found that patients with poor clinical results had a lower peak abduction moment
      (P=0.01) when tested on a dynamometer, and a higher hip abductor moment during
      gait, as percentage of peak abduction, at the affected hip than at the unaffected
      hip (P=0.047). Inefficient hip abductor function at the affected hip seems to be
      associated with poor clinical results.

PMID- 16601587
TI  - Supramalleolar osteotomy for unilateral tibial torsion.
AB  - Surgical correction of unilateral torsional deformity of the tibia is indicated
      in fewer than 1% of cases. Treatment is limited to those who have a progressive
      deformity, who are symptomatic and on whom conservative treatment has failed. We
      present the results of an osteotomy performed at the supramalleolar level leaving
      the fibula intact and held with staples. In 7 years, 13 children with a mean age
      of 13.4 years (range 10-16 years) underwent osteotomy. Six osteotomies were
      performed for internal tibial torsion (mean 25 degrees) and seven for external
      tibial torsion (mean 25 degrees). Seven participants were female and six male and
      all cases were idiopathic. One participant required antibiotics for a wound
      infection and five had the staples removed. All deformities were well corrected
      and symptoms improved. Numerous methods have been described to correct this
      deformity but all have been associated with major complications. We describe a
      supramalleolar osteotomy, leaving the fibula intact, that achieves good
      correction with minimal complications.

PMID- 16601588
TI  - Corrective supracondylar humeral osteotomies using the small AO external fixator.
AB  - Traditional methods of correcting malunited distal humeral fractures in children
      involve complex wedge osteotomies held with pins or internal fixation devices.
      These require a large exposure and challenging fixation. We elected to perform
      simple transverse osteotomies, without wedges, using a lateral incision. These
      were maintained by the small AO external fixator. Between 1987 and 2004, five
      children with malunited distal humeral fractures were treated. Angular and
      rotational correction was obtained in each case. Bony union occurred at an
      average of 8 weeks. A simple osteotomy held by the small AO external fixator
      provides accurate correction, precise adjustability, and solid stability.

PMID- 16601589
TI  - Lengthening of congenital forearm stumps.
AB  - The Ilizarov device and distraction osteogenesis method became very useful in
      correction and elongation of forearm defects. Two cases of forearm elongation
      with congenital transverse defect are described. The construction of the device
      is provided. During follow-up examination, 2 and 7 years after the treatment,
      good clinical results were achieved in both patients with the use of upper limb
      prosthesis employing the patient's own elbow joint. Presented application of the
      Ilizarov method can significantly improve possibilities for the use of prosthesis
      in patients with congenital upper limb defects and result in better cosmetic and
      functional outcome.

PMID- 16601590
TI  - Femoral and tibial lengthening by the Wagner method.
AB  - This article represents a review of the author's experience with the Wagner
      lengthening device. Forty patients between 6 and 20 years of age underwent 44
      lengthenings of the lower extremity by Wagner's technique (34 femoral and 10
      tibial) between February 1977 and January 1999. Shortening was congenital in
      origin in 24 patients. Lengthening achieved averaged 5.69 cm for the femur and
      4.3 cm for the tibia. No complication was observed in 50% of the lengthenings
      (category I). At least one complication modified the program and necessitated
      further surgery and general anesthesia in 45.45% of lengthenings (category II).
      The program was not completed in one patient and complications resulted in a
      sequela in another patient, representing 4.54% of lengthenings (category III).
      Twenty-one of the 22 lengthenings without complication were at the femur.
      Complications were more frequent in patients with a congenital origin. Many
      complications but no disastrous problems were encountered. Lengthening is better
      tolerated in children older than 10 years of age. Thirty-nine patients completed
      their program and were left with less than 2.5 cm discrepancy at the end of
      growth. The average follow-up was 8.10 years.

PMID- 16601591
TI  - Comparison of compression plate and flexible intramedullary nail fixation in
      pediatric femoral shaft fractures.
AB  - The purpose of this study was to compare the results of compression plating and
      flexible intramedullary nailing for pediatric femoral shaft fractures. Thirty
      eight consecutive patients with 40 femoral shaft fractures were evaluated. Twenty
      two femoral segments were treated with a compression plate and 18 femoral
      segments were treated with flexible intramedullary nailing. The time to healing,
      operation time and complications were evaluated. The average operation time was
      statistically significantly shorter in the nailing group (P=0.039). Four implant
      failures occurred in the compression plate group whereas one non-union was
      observed in the flexible nailing group. Flexible intramedullary nailing seems to
      provide a high union rate with a shorter operation time when compared with plate
      fixation.

PMID- 16601592
TI  - Bilateral patellar dislocation associated with alpha-mannosidase deficiency.
AB  - Mannosidosis is an extremely rare genetic disease characterized by a deficiency
      of the lysosomal enzyme, alpha-mannosidase. This enzyme is necessary for cleavage
      of mannose from many glycoproteins. In the absence of this enzyme, mannose
      accumulates in cells throughout the body, including the joints and the synovium.
      This disease causes many skeletal changes including dysostosis multiplex,
      synovial hypertrophy, and Charcot-type joints. We report the case of a girl, aged
      9 years and 6 months, who developed bilateral patellar dislocation and severe
      synovial hypertrophy secondary to alpha-mannosidase deficiency. Her disease was
      further complicated by Charcot elbow and bilateral hip and elbow avascular
      necrosis.

PMID- 16601593
TI  - Treatment of a congenital pseudarthrosis of the tibia by osteogenic protein-1
      (bone morphogenetic protein-7): a case report.
AB  - Congenital pseudarthrosis of the tibia remains one of the most difficult
      orthopaedic problems to treat. Before the use of a recombinant bone morphogenetic
      protein (bone morphogenetic protein-7; osteogenic protein-1) the patient with
      congenital pseudarthrosis of the tibia in this report had had 12 unsuccessful
      surgeries. Five months after radical resection of sclerotic tibial segments,
      Ilizarov fixation and administration of osteogenic protein-1 osteogenic device,
      the congenital pseudarthrosis of the tibia healed; at 45 months the tibia
      increased in size and the patient was fully weight bearing.

PMID- 16601594
TI  - Surgery versus surgery plus pamidronate in the management of osteogenesis
      imperfecta patients: a comparative study.
AB  - The aim of this study was to evaluate the efficacy of pamidronate in the
      management of osteogenesis imperfecta patients. This study was carried out in two
      groups. The first was treated only surgically whereas the second was treated by a
      combined approach, medical and surgical. Forty patients, divided into two groups,
      were surgically treated in order to correct bony deformities secondary to
      osteogenesis imperfecta. Group 1: twenty patients were operated at an average age
      of 6.5 years. Nine were type I, five type III and six type IV. Group 2: this
      group consisted of 20 patients to whom intermittent intravenous pamidronate were
      given at regular intervals for an average of 2 years postoperatively. The average
      age at surgery was 8.5 years. Four patients were type I, six type III, eight type
      IV, one type V and the remaining one type VII. The results were assessed
      according to a scoring system suggested and used by the authors since 1999. Group
      1: we had three good, nine fair and eight poor results. Group 2: we had 11
      excellent, four good and five fair results. The Bone mineral dens (BMD) increased
      by an average of 35.2% (22.7-112%), and the rate of refracture decreased. Best
      results in the management of patients can be obtained through the combined
      approach (surgical and medical treatment). We now advise preoperative and
      postoperative pamidronate for these patients.

PMID- 16601595
TI  - The risk of neuro-orthopaedic malformations following in-vitro fertilization.
AB  - The purpose of this study was to assess the risk of neuro-orthopaedic
      malformations after in-vitro fertilization. We compared the prevalence of neuro
      orthopaedic malformations in two groups of pregnancies conceived either naturally
      or by in-vitro fertilization, and used multivariate analysis to study the impact
      of each variable. The results showed a prevalence of 0.89% neuro-orthopaedic
      malformations in the in-vitro fertilization cohort and 0.32% in the natural
      conception cohort. The three times greater risk of malformations in the in-vitro
      fertilization cohort was reduced after adjustment to other variables. We
      concluded that the increased risk of neuro-orthopaedic malformations after in
      vitro fertilization is not due to the technique itself but rather to factors
      associated with it.

PMID- 16601596
TI  - Successfully climbing the academic leadership ladder.
AB  - Many new nursing leaders assuming deanship, assistant deanship, or interim
      deanship have limited education, experience, or background to prepare them for
      the job. To assist new deans and those aspiring to be deans, the authors of this
      department, 2 deans, offer survival tips based on their personal experiences and
      insights. They address common issues, challenges, and opportunities that face
      academic executive teams, such as negotiating an executive contract, obtaining
      faculty lines, building effective work teams, managing difficult employees, and
      creating nimble organizational structure to respond to changing consumer,
      healthcare delivery, and community needs. The authors welcome counterpoint
      discussions with readers.

PMID- 16601597
TI  - Planning and implementing an evidence-based project.

PMID- 16601598
TI  - Using creative strategies to prepare faculty for an NLNAC team visit.

PMID- 16601599
TI  - Assessing dynamic mental models: unfolding case studies.
AB  - Excellence in critical thinking skills requires well-developed situational mental
      models: integrated knowledge of how concepts and principles relate to a specific
      client's condition and care. The authors describe the use of unfolding case
      studies as a strategy for eliciting and evaluating students' changing mental
      models. Unfolding cases offer a practical method for capturing the dynamic nature
      of situational mental models and revealing significant errors in students'
      problem-solving cognitions that would not otherwise be obvious.

PMID- 16601600
TI  - Licensure is not synonymous with professionalism: it's time to stop the
      hypocrisy.
AB  - Most professional disciplines are defined by the educational degree required to
      practice. Unfortunately, nursing is not one of those disciplines. To that end,
      the authors discuss the contribution multilevel entry into practice has on
      nursing's negative appeal to the emerging workforce and the misconception that
      licensure equates with professional status. They then propose a workable solution
      to the problem.

PMID- 16601601
TI  - Strategies for online teaching and learning: lessons learned.
AB  - Distance learning and Web-based learning are accepted components of the American
      higher educational system. Strategies for teaching and learning in this medium
      require a different perspective on the teacher-student relationship and the
      educational process. The authors describe an innovative online learning endeavor
      focusing on a specialty practice area in contemporary healthcare: wound, ostomy,
      and continence nursing. Special emphasis is placed on the teaching-learning
      approaches that were successfully incorporated into the program.

PMID- 16601602
TI  - Making groups work in the classroom.
AB  - Although often part of course requirements, group work can present problems for
      students and faculty and is not always a positive learning experience. Lack of
      member motivation to work in a group situation, generational differences between
      members, and scheduling problems can impact the learning that takes place during
      a group project. The author discusses several interventions to ameliorate these
      problems.

PMID- 16601603
TI  - Sheriff's deputies and nursing students: service-learning partnership.
AB  - An innovative community health experience was provided through a collaborative
      partnership between the Richland County Sheriff's Department and the University
      of South Carolina College of Nursing. The authors discuss this unique experience.

PMID- 16601605
TI  - Integrating clinical experiences into the concept mapping process.
AB  - Clinical nursing education allows students to integrate classroom theory into
      clinical practice. The process of concept mapping allows the student to
      synthesize clinical experiences by continually modifying a preconference diagram
      or map. Through faculty support and guidance, the student can incorporate
      assessment data, research findings, and individual values and beliefs into the
      concept map. Postconference discussion provides opportunities for the student to
      complete a final evaluation of the learning process. The author discusses ways a
      concept map can change throughout the clinical day as the student gains knowledge
      and confidence through patient interaction.

PMID- 16601606
TI  - Helping nurses use NANDA, NOC, and NIC: novice to expert.
AB  - The electronic health record (EHR) requires the use of standardized nursing
      languages such as NANDA, NOC, and NIC. Helping nurses use these languages for an
      EHR requires different educational strategies in 3 domains: intellectual,
      interpersonal, and technical. The author explains the rationale for changes in
      educational methods, expectations that educators and managers should set for
      students and nurses at various levels of expertise, and teaching strategies in
      each of the domains.

PMID- 16601607
TI  - Form follows function or does it?
AB  - Many new nursing leaders assuming deanships, assistant or interim deanships have
      limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department,
      2 deans, offer survival tips based on their personal experiences and insights.
      They tackle common issues, challenges, and opportunities that face academic
      executive teams, such as negotiating an executive contract, obtaining faculty
      lines, building effective work teams, managing difficult employees, and creating
      nimble organizational structure to respond to changing consumer, healthcare
      delivery, and community needs. The authors welcome counterpoint discussions with
      readers.

PMID- 16601608
TI  - Nursing research: improving interest and understanding for the Net Generation.

PMID- 16601609
TI  - Active participation in a research study: a teaching strategy.
AB  - As nurse educators, it is necessary to make the connection between nursing theory
      and nursing practice. By implementing a new teaching strategy in a nursing
      research course, faculty researchers were able to accomplish 3 goals: (1) get
      students excited about the research process and view its relevance to nursing
      practice; (2) understand how all nursing and medical interventions begin with
      research; and (3) enlist student help on a faculty-sponsored research project.
      The authors discuss the project and its outcomes.

PMID- 16601610
TI  - Preparing for clinical: Just-in-Time.
AB  - Clinical nurse educators are expected to prepare students for the realities of
      practice while providing meaningful learning experiences. However, shortened
      patient stays in the acute care setting often lead to wasted and useless effort
      for both instructors and students. The application of Just-in-Time principles
      offers a viable and alternative solution for clinical practice preparation in
      today's rapidly changing healthcare environment.

PMID- 16601611
TI  - Mentoring adjunct faculty: innovative solutions.
AB  - Rising enrollments in schools of nursing have increased the demand for qualified
      nursing faculty. In the midst of a nurse faculty shortage, many academic
      institutions are relying on adjunct faculty to fill the gap. The increasing
      number of adjunct faculty and their need for orientation to the faculty role
      presents a challenge to schools and departments of nursing. The authors discuss
      innovative solutions to these challenges.

PMID- 16601612
TI  - Active Learning in Nursing Education (ALINE).
AB  - ALINE is a pedagogical model developed to aid nursing faculty transition from
      passive to active learning. Based on the constructionist theory, ALINE serves as
      a tool for organizing curriculum for online and classroom-based interaction and
      positioning the student as the active player and the instructor as the
      facilitator of nursing competency.

PMID- 16601613
TI  - Point system versus legal system: an innovative approach to clinical evaluation.
AB  - Faced with increasing attendance and tardiness problems in an undergraduate
      student nursing clinical setting, the authors implemented a "point system" policy
      to objectively evaluate student performance. The authors discuss the policy,
      based on area hospital attendance point systems, and its impact.

PMID- 16601614
TI  - An obstetric simulation experience in an undergraduate nursing curriculum.
AB  - Educators face the dilemma of conveying didactic information in concise, creative
      ways that evoke critical thinking. In addition, high patient acuity, coupled with
      a growing nursing shortage, requires assimilation of didactic knowledge into
      sound clinical judgment in a timely manner. Human simulation offers a creative
      teaching modality that allows transference of textbook knowledge into a real-life
      situation where nursing students can function in their role without untoward
      effects to their clients. The author illustrates the use of a human birthing
      simulator, Noelle, in an undergraduate nursing program as a creative and
      effective teaching strategy.

PMID- 16601615
TI  - Comparison of traditional and accelerated baccalaureate nursing graduates.
AB  - Accelerated nursing programs have been one effort to attract nursing students.
      The author discusses the results of the study that compared traditional to
      accelerated students to determine their success on the NCLEX-RN.

PMID- 16601616
TI  - Teaching adolescents about adolescence: experiences from an interdisciplinary
      adolescent health course.
AB  - As abstract reasoning increases in complexity, adolescents may face dissonance
      between new thoughts and prior beliefs. Students in the health professions may be
      forced to resolve these dissonances in order to execute their professional
      responsibilities. In developing an undergraduate interdisciplinary course on
      adolescent health, the authors anticipated challenges in teaching adolescents
      about adolescence. Over the course of the semester, the anticipated challenges
      became reality. The author discusses pertinent developmental theories and their
      application in facilitating late adolescent identity formation and professional
      role development.

PMID- 16601617
TI  - Lessons learned from collaborative testing.
AB  - Is collaborative testing a valuable tool for use within nursing education? This
      study discusses the lessons learned from the use of collaborative testing with
      sophomore nursing students in their first medical-surgical nursing course.
      Although the findings did not necessarily support previous research in all areas,
      the students reported development of collaborative and communication skills as
      well as critical thinking and conflict management.

PMID- 16601618
TI  - The value of peer review.

PMID- 16601619
TI  - Challenges in language, culture, and modality: translating English measures into
      American sign language.
AB  - BACKGROUND: Few health-related questionnaires have been translated into American
      Sign Language (ASL), precluding Deaf adults from full participation in health
      related research. OBJECTIVES: To translate self-report measures (written English)
      into sign language and to evaluate the equivalence of the ASL versions to the
      original English versions of the measures. METHODS: A descriptive-comparative
      design with a derived etic (outsider) perspective was used to evaluate
      equivalency between the English version of the Self-Rated Abilities for Health
      Practices (SRAHP) and an ASL version. Both versions were administered to 24
      bilingual (English and ASL) adults. Analysis included correlation between total
      scores and comparison of internal consistency of both versions; psychometric
      properties of the signed SRAHP were computed for 105 Deaf adults who participated
      in a study of the Deaf Heart Health Intervention (DHHI). RESULTS: The correlation
      between total scores on ASL and English versions was .92, item-to-total
      correlations ranged from .08 to .80 on the English version and from .33 to .80 on
      the ASL version. Cronbach's alpha was .91 for the English version and .90 for the
      ASL version. Mean scores on the ASL version were significantly lower for the all
      Deaf DHHI sample (n = 105) than for the bilingual subjects (n = 24) although
      internal consistency remained high (Cronbach's alpha of .93 and item-to-total
      correlation of .38-.74) for the new ASL version. DISCUSSION: The use of an
      adapted translation model resulted in a sound ASL version of a health-related
      measure. Results support use of the derived etic strategy for translating
      measures from their original language into new languages. The approach is also
      appropriate for changing modalities from written form to other modalities, such
      as the visual-manual modality of ASL.

PMID- 16601620
TI  - Is the Nursing Work Index measuring up? Moving beyond estimating reliability to
      testing validity.
AB  - BACKGROUND: The Nursing Work Index (NWI) provided the foundation for three
      published instruments, each presented as a valid measure of the nursing practice
      environment. Aiken and Patrician [Aiken, L. H., & Patrician, P. A. (2000).
      Measuring organizational traits of hospitals: The Revised Nursing Work Index.
      Nursing Research, 49, 146-153] revised the NWI to the Revised Nursing Work Index
      (NWI-R), reporting four conceptually derived subscales. Lake [Lake, E. T.(2002).
      Development of the Practice Environment Scale of the Nursing Work Index. Research
      in Nursing and Health, 25,176-188] used factor analysis to empirically derive
      five subscales with a composite overarching practice environment factor.
      Estabrooks et al. [Estabrooks, C. A., Tourangeau, A. E., Humphrey,C. K., Hesketh,
      K. L., Giovannetti, P., Thomson, D., et al. (2002). Measuring the hospital
      practice environment: A Canadian context. Research in Nursing and Health, 25, 256
      268] reported a single empirically derived factor solution that represented the
      nursing practice environment. OBJECTIVE: To examine the validity of three
      instruments (based on the NWI) as measures of the nursing practice environment.
      METHODS: The measurement models underlying the three instruments were
      reconstructed from the information provided by each author in published
      manuscripts and then were estimated using structural equation modeling (SEM), the
      chi-square test of model fit, and data from the 1998 Canadian Nurse Survey.
      RESULTS: Each of the three underlying measurement models was factor analytic in
      design (multiple indicators of each concept) and failed significantly when
      compared with the data (Aiken & Patrician; chi2 = 939.12, p <.001, df = 50; Lake,
      chi2 = 17,872.73, p <.001, df = 319; Estabrooks et al., chi2= 38,590.29, p
      <.001). This lack of model fit with the data raises questions about the validity
      of these instruments as measures of the nursing practice environment. DISCUSSION:
      The nursing practice environment is complex and has been examined inadequately by
      factor-analytic approaches, largely because insufficient attention has been paid
      to implicit underlying theory. The development and testing of robust theory using
      powerful research methods available to examine causal relationships in complex
      theoretical models will advance understanding of constructs such as the nursing
      practice environment.

PMID- 16601621
TI  - Factors which influence Latino community members to self-prescribe antibiotics.
AB  - BACKGROUND: Although there is consistent evidence of a link between antibiotic
      use and increasing antimicrobial resistance in the community, inappropriate use
      of antimicrobials continues to be a global problem. OBJECTIVE: To describe
      knowledge, attitudes, and practices of Latino community members in upper
      Manhattan regarding use of antibiotics. METHODS: Written questionnaires and eight
      focus groups comprised of Hispanic community members (three groups), bodega
      employees, and healthcare providers (one group) in a Latino neighborhood in New
      York City. RESULTS: There were major knowledge deficits regarding use of
      antibiotics. Informants reported taking antibiotics for pain or other conditions
      as well as for symptoms of infection. Antibiotics were frequently obtained from
      bodegas without prescription, but generally only for adults, not for children.
      DISCUSSION: Interventions to improve antibiotic use that are focused on the
      formal healthcare system (e.g., clinicians, pharmacists, persons with health
      insurance) are unlikely to be effective with recently immigrated Latino community
      members. Successful interventions for this population should include targeted
      messages to bodega employees, community organizations, and children and their
      parents.

PMID- 16601622
TI  - Buried alive: the presence of nursing on hospital Web sites.
AB  - BACKGROUND: Increasingly, hospitals are using sites on the World Wide Web (Web)
      to market their services and products and to advertise employment opportunities.
      These Web sites are a potential resource for information on the hospitals'
      nursing care and nurses' impact on patient outcomes. OBJECTIVE: The aim of this
      study was to explore the presence of nursing-accessible and visible data on
      nurses, nursing practice, or nursing care-on hospital Web sites. METHODS: A
      random sample of 50 hospital Web sites from the U.S. News and World Report's 2003
      list of America's best hospitals was examined. A tool developed to capture the
      characteristics that denote a presence of nursing was used to examine hospital
      Web sites. RESULTS: All 50 sites had at least two occurrences of visible data in
      the form of pictures, graphics, or text that related to nurses, nursing care, or
      nursing practice. However, nurse-related content on these hospital Web sites was
      minimally to somewhat present and was frequently located on pages deep within the
      site. DISCUSSION: The presence of nursing on hospital Web sites could represent
      the importance of nursing, nursing practice, or nursing care for patients
      entering hospital systems. Instead, nursing content on hospital Web sites
      primarily focuses on nursing employment.

PMID- 16601623
TI  - Predictors of physical activity in older adults with borderline hypertension.
AB  - BACKGROUND: Physical activity (PA) is effective in controlling blood pressure
      (BP) and is important in the treatment and prevention of hypertension in the
      elderly. Reasons for engaging in regular PA are complex and are influenced by
      personal, interpersonal, and environmental factors. OBJECTIVE: To test a
      predictive model of PA in older adults with borderline hypertension. METHODS:
      Data were collected from a multiethnic nonprobability sample of 267 men and women
      60-75 years of age. The predictor variables were gender, ethnicity, income,
      previous exercise experience, self-efficacy for PA, perceived health status,
      awareness of BP, barriers to PA, intrinsic motivation for health, motivation for
      PA, interpersonal influence, and environmental influence. RESULTS: The
      hypothesized model was tested and modified using path analysis. The final model
      explained 44% of the variance in PA. The variables that directly predicted PA
      were gender, income, previous exercise experience, self-efficacy for PA, and
      motivation for PA. Variables that indirectly predicted PA were perceived health
      status, barriers to PA, self-efficacy for PA, intrinsic motivation for health,
      and environmental influence. CONCLUSIONS: The significant associations between
      the cognitive appraisal and motivation concepts extend previous research and add
      to the understanding of the complex factors that influence regular PA. The PA
      model can be a foundation for further research and practice.

PMID- 16601624
TI  - The impact of farm lifestyle and health characteristics: cervical cancer
      screening among southern farmwomen.
AB  - BACKGROUND: Rural residence, access to healthcare facilities, and multiple roles
      of farmwomen may pose barriers to cervical cancer screening among women living in
      southern farm states. OBJECTIVES: To compare the proportion of women failing to
      obtain cervical cancer screening in three Southern states to state-level
      Behavioral Risk Factor Surveillance System (BRFSS) data and to identify factors
      contributing to cervical cancer screening and detection behaviors. METHODS: A
      cross-sectional study design was used. Data were collected using several Farm
      Family Health and Injury Prevention surveys via telephone interviews in three
      southern states. Farmwomen (N = 2,324) from three states comprised the sample on
      Pap testing. Data were used from summary reports of the BRFSS for each state to
      compare the proportion of farmwomen >or=18 years of age who had failed to obtain
      a Pap test within the past 3 years to failure to obtain Pap tests statewide.
      Multiple logistic regression analyses were conducted to examine the predictors of
      failure to obtain early screening. RESULTS: Pap testing did not meet Healthy
      People 2010 target goal of 90%. Farm lifestyle predicting failure to obtain
      cervical cancer screening included having a house on the farm and engaging in no
      off-farm work and minimal involvement in farm tasks. The risk of failing to
      obtain Pap testing increased with age and decreased with education. The only
      health access variable contributing to failure to obtain Pap testing was women
      with no insurance. Positive preventive risk factors contributing to compliance
      with up-to-date status were previous mammogram and previous breast exam. Being
      married was a positive risk factor. DISCUSSION: Although the failure to obtain
      Pap testing in Texas was comparable to state BRFSS rates, failure to obtain Pap
      testing rates in Kentucky and Louisiana were at least 6% greater for farmwomen
      than women living in the state. Farmwomen, a subgroup of the rural population,
      have unique barriers to obtaining screening services. Geographical isolation and
      minimal role involvement on the farm may contribute to the likelihood that women
      are not seeking cervical cancer screening.

PMID- 16601625
TI  - Measurement of nurse job satisfaction using the McCloskey/Mueller Satisfaction
      Scale.
AB  - BACKGROUND: Originally developed to rank rewards that nurses value and that
      encourage them to remain in their jobs, the McCloskey/Mueller Satisfaction Scale
      (MMSS) is being used extensively in research and practice to measure nurse job
      satisfaction. Since its original development in 1990, limited evidence of
      psychometric properties of the MMSS has been reported. OBJECTIVE: To investigate
      and report the psychometric properties of the MMSS when used in 2003 to measure
      hospital nurse job satisfaction. METHODS: Data from a survey of 8,456 nurses were
      used to establish psychometric properties of the MMSS. Dimensionality was tested
      using confirmatory and exploratory factor analyses. Validity of new MMSS factors
      was tested by investigating relationships of the new factors with theoretically
      related concepts and by testing ability of the new factors to predict nurses'
      intentions to remain employed in their hospitals. Reliability coefficients of the
      new factors are reported. RESULTS: The original eight factors could not be
      replicated satisfactorily using confirmatory factor analysis. Exploratory factor
      analysis found a seven-factor model rather than the original eight factors
      previously reported. Validity of this new model was supported. However, similar
      to the original instrument, weak internal consistency reliability coefficients
      were found for three of the new MMSS factors. DISCUSSION: From a research
      perspective, using an instrument with 23 items that measure 7 aspects of nurse
      job satisfaction is more desirable than an instrument with 31 items. However,
      MMSS items must be redeveloped to improve internal consistency of factors.

PMID- 16601626
TI  - Relationships of work and practice environment to professional burnout: testing a
      causal model.
AB  - BACKGROUND: Research has established clear links between nurses' experience of
      professional burnout and many qualities of work environments but more work is
      needed to clarify interrelationships among aspects of complex organizational
      settings. OBJECTIVE: To test a nursing worklife model that defined structured
      relationships among professional practice environment qualities and burnout.
      METHODS: Hospital-based nurses in Canada (N = 8,597) completed an assessment of
      worklife (Nursing Work Index, NWI) and burnout (Maslach Burnout Inventory-Human
      Service Scale, MBI-HSS). RESULTS: A causal model was used to confirm the factor
      structure of the Professional Environment Scale (NWI-PES) on a subset of NWI
      items and the factor structure of the MBI-HSS. The analysis provided support for
      a structural model (nursing worklife model) linking the five worklife factors
      used to define a fundamental role for nursing leadership in determining the
      quality of worklife regarding policy involvement, staffing levels, support for a
      nursing model of care, and physician-nurse relationships. The analysis supported
      a direct path (negatively weighted) from staffing to emotional exhaustion and a
      direct path (positively weighted) from nursing model of care to personal
      accomplishment. DISCUSSION: Implications for refining a model of worklife are
      discussed. Implications for enhancing the quality of worklife and supporting
      engagement with work are considered.

PMID- 16601628
TI  - Challenges to intervention implementation: lessons learned in the Bathing Persons
      with Alzheimer's Disease at Home study.
AB  - BACKGROUND: The pressing need for interventions to improve outcomes for
      vulnerable caregivers of individuals with Alzheimer's disease (AD) is hindered by
      inadequate knowledge of variables affecting intervention delivery, receipt, and
      enactment. OBJECTIVE: To analyze intervention implementation issues encountered
      within the Bathing Persons with Alzheimer's Disease at Home (BATH) study.
      METHODS: The BATH study, a home-based, randomized, controlled trial of
      interventions to improve behavioral symptoms and caregiver self-efficacy,
      consisted of 130 intervention visits to 42 care recipients-caregiver dyads. Data
      include direct observation, nurse interventionist field notes, case analyses, and
      caregiver journals, reflecting various perspectives. Content analysis was used to
      identify key treatment process themes. RESULTS: Issues that affected the
      delivery, receipt, and enactment of interventions reflect the intersection of in
      vivo caregiving and research design. DISCUSSION: The primary lessons learned
      were: (a) early identification of caring dyads prior to crisis must be improved;
      (b) in vivo observation is essential to individualized interventions targeting
      behavioral etiologies and developing caregiver skills; (c) intervention delivery
      depends on the nurse interventionist's skills and a flexible, trusting researcher
      dyad relationship; (d) complex caregiver situations affect treatment receipt and
      enactment; and (e) intervention enactment requires coaching, practice, and
      support over time. These findings help to explain issues impacting intervention
      implementation to a vulnerable population. Recommendations for intervention
      research design to maximize internal and external validity in real-life care
      contexts can inform future outcome studies, aid in the search for improved care,
      and lead to supportive public policy for families living with AD.

PMID- 16601629
TI  - Fidelity to a 12-week structured medication adherence intervention in patients
      with HIV.
AB  - BACKGROUND: Researchers have been conducting efficacy and effectiveness studies
      on interventions that address medication-taking behavior in patients with HIV
      infection. However, they also must examine the fidelity to the research protocol
      for the delivery of the intervention. OBJECTIVES: The aims of this study were to
      determine the level of fidelity to each of the specified end points (number of
      intervention sessions, session duration, number of telephone calls per session,
      the length of time between sessions, sessions with multiple interventions, and
      attrition from the intervention protocol) in the delivery of the 12-week, nurse
      delivered, structured telephone intervention designed to improve medication
      adherence and to determine the factors (race, gender, and socioeconomic status)
      related to participation in the intervention. METHODS: This descriptive
      correlational study was a substudy of a larger randomized clinical trial (N =
      200) testing the effectiveness of a 12-week nurse-delivered intervention designed
      to improve medication adherence to antiretroviral medications in persons with HIV
      infection. The Intervention Tracking Form was used to collect data on all
      intervention delivery end points during the delivery of the structured
      intervention. A sociodemographic questionnaire was used to collect the
      sociodemographic characteristics of the sample. RESULTS: Two thirds of the sample
      (n = 66) were male, and slightly more than half were White. The average age was
      39.68 (SD = 7.98) years. The average number of intervention sessions delivered
      was 8.1 (SD = 4.07). Participants were more likely to receive the first five
      intervention sessions (n = 77, 77.8%), and 21 (21.2%) dropped out of treatment
      before it was completed. Nearly one quarter (n = 24, 24.2%) of the sample had
      doubled-up interventions. Intervention sessions lasted, on average, 11.3 min.
      Typically, more than one telephone call was needed before the participant was
      reached (M = 2.2). The mean number of days between sessions was 11.5 days. Women
      were more likely to have doubled-up interventions (p = .036). There was a
      marginally significant difference (p = .075) in the number of sessions received
      between the Whites and non-Whites: Whites (M = 8.8, SD = 3.9) received slightly
      more sessions compared with non-Whites (M = 7.24, SD = 4.2). When examining the
      interaction effects between the demographic factors considered, a race-by-income
      effect was observed for the mean number of attempts to contact the participant (p
      = .044). DISCUSSION: These results demonstrate a lack of fidelity to the research
      intervention protocol. Factors beyond the researchers' control may have
      influenced fidelity to the intervention protocol.

PMID- 16601630
TI  - Prospective study of quality of life of patients receiving treatment for prostate
      cancer.
AB  - BACKGROUND: No research was found that compared quality of life (QOL) outcomes of
      prostate cancer patients receiving intensity-modulated radiation therapies with
      prostate cancer patients receiving radical prostatectomy. OBJECTIVES: To (a)
      describe differences in QOL before and after three types of treatment for
      prostate cancer: radical prostatectomy, intensity-modulated radiation therapy +
      seed implantation (permanent brachytherapy), or intensity-modulated radiation
      therapy + high dose rate radiotherapy (temporary brachytherapy); and (b)
      investigate demographic, physical, and psychosocial variables that impact QOL of
      men with prostate cancer. METHODS: Data were collected on three occasions:
      baseline (prior to treatment), 1 month, and 3 months after beginning treatment.
      Measures included biographic data, physiological, and psychological measures.
      Analysis of variance and hierarchical regression were used to examine patterns,
      describe differences, and identify predictors of QOL in the three treatment
      groups. QOL was conceptualized as a multidimensional construct that included
      physical, psychological, social, and functional well-being and prostate cancer
      concerns. RESULTS: Groups differed significantly in bowel and urinary symptom
      scores and prostate cancer concerns at baseline, and in urinary and depressive
      symptoms at 3 months. There were no significant group differences at 1 month.
      DISCUSSION: Significant differences were found in QOL as measured with the
      Functional Assessment of Cancer Treatment-Prostate after treatment with radical
      prostatectomy, intensity-modulated radiation therapy + seed implantation, or
      intensity-modulated radiation therapy + high dose rate radiotherapy. Findings may
      provide healthcare providers with knowledge about treatment sequelae for prostate
      cancer, enable healthcare providers to educate patients about QOL outcomes of
      treatment for prostate cancer, and enable patients to make more informed
      treatment decisions.

PMID- 16601631
TI  - Postpartum depression treatment rates for at-risk women.
AB  - BACKGROUND: Despite growing awareness of postpartum depression (PPD), screening
      is not yet standard care and evidence that screening produces improved health
      outcomes remains limited. OBJECTIVES: To examine mental health treatment rates at
      3 and 4 months postpartum for women who were identified with PPD symptoms at 2 to
      4 weeks after delivery. METHODS: A secondary analysis of data from a mother
      infant intervention study for women with PPD symptoms was conducted. Postpartum
      women were screened for PPD symptoms; women with positive PPD screens were
      assessed at 2, 3, and 4 months postpartum. Research nurses monitored symptoms and
      encouraged and assisted women who experienced moderate to severe PPD symptoms to
      seek evaluation and mental health referral from their primary care providers.
      RESULTS: From the screening of a community-based population of 1,215 postpartum
      women, 122 women identified as having PPD enrolled in the clinical trial and 117
      participated in all assessments. At 3 and 4 months postpartum, only 14 women
      (12%) received psychotherapy and fewer received psychopharmacologic treatment. In
      comparison to women with low PPD symptoms, significantly more women with high PPD
      symptoms were in therapy at 3 and 4 months. DISCUSSION: The inadequacy of
      treatment rates among a sample of at-risk women raises grave concern. Possible
      barriers to referral and treatment include clinician and healthcare system, third
      party payment, and personal factors. Evaluating health outcomes from PPD
      screening and testing approaches designed to increase treatment participation are
      warranted.

PMID- 16601632
TI  - Research on the frontlines of healthcare: a cooperative learning approach.
AB  - BACKGROUND: Evidence-based practice is a common goal in hospitals, but learning
      about research so that the practice can be done is often challenging for
      clinicians. OBJECTIVES: The aims of this study were to (a) develop a process that
      supports organizational and staff development while conducting research and (b)
      conduct a research study in the emergency department (ED) to examine patient
      population, satisfaction, and waiting room issues. METHODS: A multidisciplinary
      team of clinicians and scientists was assembled to learn and do research while
      evaluating the ED waiting room of a Level I trauma center. A cooperative learning
      method approach was used to teach research concepts as the study was designed and
      implemented. RESULTS: The team demonstrated their knowledge and understanding of
      research concepts by being involved actively in the creation and implementation
      of the preintervention study. Using information from photographs, observations,
      and a questionnaire, the team identified the following key dissatisfaction areas:
      (a) atmosphere (including comfort with environment, neatness and cleanliness, and
      noise), (b) telephones, (c) parking and thoroughfare, (d) professional behavior
      and staff presence (including personal attention), (e) security, and (f) triage
      and confidentiality. DISCUSSION: The model of working in partnership with
      researchers and using cooperative, collaborative research is an effective way to
      evaluate and address issues related to quality of care while learning about the
      research concepts needed to put evidence into practice.

PMID- 16601633
TI  - Applying an evaluation framework for health information system design,
      development, and implementation.
AB  - BACKGROUND: Dramatic advances in health information technologies necessitate a
      comprehensive evaluation framework covering all phases of development, from
      conception to routine operational use. OBJECTIVES: The purpose of this article
      was to illustrate the application of an informatics evaluation framework that
      provides a heuristic for matching the stage of system design and the level of
      evaluation. METHODS: An evaluation framework is illustrated in the context of
      five studies in different stages of system design. RESULTS: The studies discussed
      in this article represent the various stages of the framework. In addition, they
      are examples of how evaluation research studies not only contribute to the
      assessment of system design but also constitute distinct contributions to
      knowledge. DISCUSSION: The ability to engineer advanced information systems has
      exceeded the understanding of how to deploy them effectively in complex settings
      and to adapt them to a range of user populations. A systematic, continuous
      evaluation increases the likelihood that the conditions for success will be
      understood, including how to tailor a system, how to maintain the target
      population's use of the system, and how to innovate continually to enhance the
      functionality of the system and the users' experience. Without sound evaluation
      methodologies throughout the stages of system development, information systems
      have limited potential to influence healthcare processes positively.

PMID- 16601634
TI  - Exemplars of mixed methods data combination and analysis.
AB  - BACKGROUND: Mixed methods research approaches can be applied to nursing and
      healthcare. Multiple perspectives and different types of data (e.g., social
      behavioral data, numerical outcome measures, or clinical variables) often are
      needed to examine complex clinical problems and health behaviors fully. Although
      qualitative and quantitative methods are recognized widely as complementary for
      studying and explaining human phenomena, methodological techniques for combining
      and analyzing mixed methods data have received less attention. OBJECTIVES: To
      describe techniques for mixed methods data combination and analyses using three
      different design approaches. METHODS: Data combination and analysis techniques
      are presented using the following approaches: (a) mixed methods event analysis,
      (b) concurrent-mixed analysis for complementarity and completeness, and (c)
      concurrent nested analysis to provide a broader understanding of phenomena and
      enrich the description of participants. RESULTS: Research exemplars from topical
      areas such as weaning from long-term mechanical ventilation, medication-taking
      among community-dwelling persons with dementia, health control beliefs after lung
      transplantation, and recovery from subarachnoid hemorrhage are presented. Simple
      and complex matrix construction and a variety of graphical displays are used to
      illustrate data combination and analysis techniques for mixed methods research.
      DISCUSSION: The techniques for mixed methods data combination and analysis
      presented have the potential to advance the use and refinement of mixed methods
      research, thereby expanding the repertoire of methodologies to study complex
      phenomena of interest to nurses.

PMID- 16601635
TI  - Generating new knowledge from existing data: the use of large data sets for
      nursing research.
AB  - BACKGROUND: An unprecedented amount of data from a variety of disciplines
      containing variables of interest to nursing are available to nurse researchers.
      In response, the use of large data sets is emerging as a legitimate method that
      can help facilitate the translation of knowledge to practice. OBJECTIVE: To
      explore the spectrum of methodological issues and practical applications
      encountered by three nurse researchers using secondary data analysis of three
      existing large data sets as a means to ask new questions and generate new nursing
      knowledge. METHODS: Three research studies using the analysis of three existing
      large data sets were described. The following are discussed: developing a
      theoretical framework, selecting an appropriate data set, operationalizing and
      measuring variables, preparing data for analysis, and identifying threats to
      validity and reliability. RESULTS: Although the use of existing data may shorten
      the time from question to answer, the research process remains the same. The
      three research studies were used to illustrate conceptual congruence, threats to
      internal and external validity, and threats to reliability and generalizability.
      DISCUSSION: Data obtained from a variety of disciplines and for a variety of
      reasons can and should be used to answer nursing practice and research questions.
      Using existing large data sets offers nurse researchers a unique opportunity to
      ask and answer questions that can affect how nurses care for patients in a time
      effective and cost-efficient manner. Exploring the spectrum of methodological
      issues and practical applications involved in this work will help guide nurse
      researchers through the process.

PMID- 16601636
TI  - Translating best practices in nondrug postoperative pain management.
AB  - BACKGROUND: The research-to-practice gap is at the heart of the problem in the
      underuse of nondrug complementary methods to manage postoperative pain. PURPOSE:
      To show how the six steps of the Collaborative Research Utilization (CRU) model
      can be used to translate research into practice, using an example of nondrug pain
      management protocols. METHODS: The CRU model was used to translate empirically
      tested nondrug interventions for surgical pain management enhancement into cost
      effective, easy-to-use, best-practice nursing interventions, using tailored
      patient teaching. RESULTS: The preliminary findings of the substudy in the
      context of the CRU model are reported. DISCUSSION: The CRU model was successful
      in changing patients' knowledge, attitudes, and use of nondrug interventions for
      pain management. Further research is needed in heterogeneous populations.
      Organization receptivity to research and a well-integrated computerized
      documentation system for cueing clinicians' pain management practices are key for
      effectiveness of change.

PMID- 16601637
TI  - Vaginal or cesarean birth? Application of an advocacy organization-driven
      research translation model.
AB  - BACKGROUND: Research translation models are needed to demonstrate a process for
      identifying and communicating high-quality scientific evidence that enables
      informed involvement of relevant stakeholders, including informed consumer
      participation in healthcare decision making. PURPOSE: To describe the rationale
      for, and elements of, a research translation model, as it is being applied to
      inform and support diverse end users with respect to decisions relating to
      vaginal versus cesarean birth. METHODS: The Maternity Center Association (MCA),
      the oldest national United States organization advocating on behalf of mothers
      and babies, identified the need to clarify and translate into practice best
      evidence about relative harms of cesarean and vaginal birth. MCA developed a
      model that included engaging leading stakeholder groups, conducting a systematic
      review to fill research gaps, and initiating an education and advocacy campaign
      to reach consumers, health professionals, and the general public with review
      results and related information and guidance. International standards for
      systematic reviews and evidence about effective professional practice, use of
      decision aids, and risk communication were used. RESULTS: Dozens of harms that
      differ by mode of delivery, with nearly all favoring vaginal birth, were found
      during review. Without clear, compelling, and well-supported justification for
      cesarean section, vaginal birth is the safest way for women to give birth and
      babies to be born. Despite modest resource expenditure, the implemented model is
      bringing review results to many individuals and organizations, incorporating
      elements that have been shown to be effective. The next step is to formally
      evaluate the decision aid in clinical settings. DISCUSSION: Advocacy
      organizations are uniquely positioned to carry out research translation. Given
      the importance of research translation and the challenges of carrying out this
      work, programs and policies should be established to support and evaluate
      advocacy organizations in this role.

PMID- 16601638
TI  - Nursing-sensitive outcomes data collection in acute care and long-term-care
      settings.
AB  - BACKGROUND: Most administrative databases do not contain good information about
      nursing-sensitive outcomes. OBJECTIVES: To determine (a) the reliability of the
      instruments measuring nursing-sensitive outcomes, (b) whether the outcome
      measures are sensitive to changes in patients' health, and (c) whether the
      outcome measures are associated with nursing interventions. METHODS: The sample
      consisted of 890 patients from acute care hospitals and long-term-care
      facilities. A repeated measures design was used. Functional status was assessed
      on admission and discharge using Minimum Data Set 2.0 items. Symptom (pain,
      nausea, dyspnea, fatigue) frequency and severity were assessed with 4-point and
      11-point numeric scales, respectively. Therapeutic self-care was assessed on
      discharge from acute care. Nursing interventions were assessed by documentation
      review. RESULTS: The outcome measures demonstrated very good interrater
      reliability with weighted Kappa ranging from .64 to .93. The internal consistency
      reliability was high for functional status and therapeutic self-care. The outcome
      tools were sensitive to change in patient condition. Select nursing interventions
      were related to functional status, therapeutic self-care, and symptom outcomes.
      DISCUSSION: The findings suggest that nurses are able to collect data on nursing
      sensitive patient outcomes in a reliable and valid way.

PMID- 16601639
TI  - Effective treatment Of OCD?

PMID- 16601641
TI  - ADHD and insomnia.

PMID- 16601642
TI  - A pilot study of adjunctive family psychoeducation in adolescent major
      depression: feasibility and treatment effect.
AB  - OBJECTIVE: To obtain preliminary evidence of the feasibility and effectiveness of
      adjunctive family psychoeducation in adolescent major depressive disorder.
      METHOD: Participants were from outpatient clinics in Hamilton and London,
      Ontario. Over 24 months, 41 adolescents ages 13 through 18 years meeting major
      depressive disorder criteria were recruited (31 in Hamilton, 10 in London).
      Participants were randomized to usual treatment or usual treatment plus family
      psychoeducation. Outcome measures were readministered at 2 weeks, mid-treatment,
      posttreatment, and 3-month follow-up. Intent-to-treat analyses used chi2 and t
      tests and growth curve analysis. Standardized effects based on growth curve
      estimates were calculated for continuous outcomes. RESULTS: The London site was
      withdrawn because of poor participant retention. In Hamilton, no participant
      missed more than one assessment and there was good family psychoeducation
      adherence. Compared to controls, participants in the experimental group showed
      greater improvement in social functioning and adolescent-parent relationships
      (with medium standardized effect size > 0.5), and parents reported greater
      satisfaction with treatment. CONCLUSIONS: There were positive treatment effects
      on family and social functioning processes postulated to mediate the clinical
      course of major depressive disorder. The study provides support for further
      evaluation of family psychoeducation in this clinical population.

PMID- 16601643
TI  - Case study: longitudinal treatment of adolescents with depression and
      inflammatory bowel disease.
AB  - OBJECTIVE: To assess longitudinal maintenance of improvements in depression,
      anxiety, global functioning, and physical health perception in 11 adolescents at
      6 and 12 months following completion of manual-based cognitive-behavioral
      therapy. METHOD: Standardized instruments assessed follow-up changes in
      depression, anxiety, physical health, and global psychological functioning.
      RESULTS: At both assessments, 10 adolescents did not meet criteria for mood
      disorders. Improvements in depression, anxiety, global functioning, and physical
      health perceptions at completion of the cognitive-behavioral therapy were
      maintained during the 12-month period. Additional cognitive-behavioral therapy
      sessions (mean = 4.36; SD = 4.37) and psychopharmacology (n = 5) were required
      during the follow-up period. CONCLUSIONS: CBT with maintenance sessions and
      medication offers promise to adolescents facing comorbid depressive and physical
      disorders.

PMID- 16601644
TI  - Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q):
      reliability and validity.
AB  - OBJECTIVE: The pediatric version of the Short Form of the Quality of Life
      Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) was developed to aid in the
      assessment of an important aspect of life experience in children and adolescents.
      METHOD: The reliability and validity of the PQ-LES-Q was tested using data from a
      sample of 376 outpatient children (6-11 years old) and adolescents (12-17 years
      old) with major depressive disorder. RESULTS: The internal consistency
      coefficients at screening, baseline, and endpoint were high (0.87, 0.90, 0.89,
      respectively) as was the 1-week test-retest intraclass correlation coefficient of
      reliability (0.78). The correlations of the PQ-LES-Q total score with concurrent
      measures of severity of illness were in the moderate range (e.g., Global Clinical
      Impression of Severity, -0.40; Children's Global Assessment Scale, 0.36;
      Children's Depression Rating Scale total score, -0.45), as were the correlations
      with measures of change between baseline and endpoint (e.g., Clinical Global
      Impression of Severity, -0.34; Children's Global Assessment Scale, 0.33;
      Children's Depression Rating Scale total score, -0.45). CONCLUSIONS: These
      findings support the use of the PQ-LES-Q as an additional measure of current
      clinical status and outcome because it taps dimensions that are not covered by
      the commonly used global severity of illness or symptomatic measures.

PMID- 16601645
TI  - Characteristics of adolescents and young adults with ADHD who divert or misuse
      their prescribed medications.
AB  - OBJECTIVE: Little is known about the risks and characteristics of attention
      deficit/hyperactivity disorder (ADHD) patients who misuse or divert their
      stimulant medications. As part of a 10-year longitudinal study of youths with
      ADHD, the authors evaluated medication diversion or misuse at the last follow-up
      period. METHOD: Structured psychiatric interviews for diagnosis and a self-report
      questionnaire regarding medication use in medicated subjects with ADHD compared
      with controls without ADHD receiving psychotropics for non-ADHD treatment were
      employed. RESULTS: Of 98 subjects receiving psychotropic medications (mean age of
      20.8 +/- 5 years), 55 (56%) were ADHD subjects and 43 (44%) were controls
      receiving medications for other purposes. The authors found that 11% of the ADHD
      group reported selling their medications compared with no subjects in the control
      group (z = 0.00, p <.05). An additional 22% of the ADHD group reported misusing
      their medications compared with 5% of the control subjects (z = 1.7 p =.09) and
      that those with conduct or substance use disorders accounted for the misuse and
      diversion. A minority of subjects reported escalating their doses and concomitant
      use with alcohol and drugs. CONCLUSIONS: The data indicate that the majority of
      ADHD individuals, particularly those without conduct or substance use disorders,
      use their medications appropriately. The authors' findings also highlight the
      need to monitor medication use in ADHD individuals with conduct and/or substance
      use disorders and to carefully select agents with a low likelihood of diversion
      or misuse in this group.

PMID- 16601646
TI  - Stimulant treatment over 5 years: effects on growth.
AB  - OBJECTIVE: Long-term effects of psychostimulants on growth in height and in
      weight are investigated in children with attention-deficit/hyperactivity
      disorder. METHOD: Participants were 79 children, 6 to 12 years of age, with
      attention-deficit/hyperactivity disorder, who were followed annually for up to 5
      years, between the years 1993 and 1994 and 1998 and 1999. Annual height and
      weight measurements were standardized by age and gender using the 2000 Centers
      for Disease Control and Prevention Growth Charts for the United States and
      reported as z scores. For children taking stimulants throughout the previous
      school year, dose potency was standardized to methylphenidate in milligrams per
      kilogram per day. We used hierarchical linear modeling to investigate the
      influence of dose and duration of stimulant treatment on the rate of growth in
      height and weight. RESULTS: Controlling for time since initiation of treatment,
      daily dose of stimulant medication was negatively associated with z scores for
      height (beta = -.11, SE = 0.03, p <.01) and for weight (beta = -.29, SE = 0.04, p
      <.01). Estimates based on the statistical model suggest that children receiving >
      or = 1.5 mg/kg/day methylphenidate will show diminished weight gain after 1 year;
      those receiving > or = 2.5 mg/kg/day methylphenidate will show diminished gains
      in height after 4 years. CONCLUSION: Long-term use of high doses of stimulants
      during a period of 1 to 5 years is likely to have measurable effects on the rate
      of growth in school-age children with attention-deficit/hyperactivity disorder.

PMID- 16601647
TI  - Analysis of electrocardiographic data following use of paroxetine in pediatric
      depression and obsessive-compulsive disorder.
AB  - OBJECTIVE: This retrospective analysis of electrocardiographic (ECG) data
      investigated the cardiovascular effects of paroxetine 10-50 mg/day in pediatric
      patients (7-18 years of age). Data were collected from three 8- to 10-week,
      randomized, placebo-controlled, double-blind trials of paroxetine in pediatric
      patients with major depressive disorder or obsessive-compulsive disorder. METHOD:
      Electrocardiograms (ECGs) were retrospectively retrieved from 63 study sites in
      the United States and Canada. Only patients with at least one screening and one
      on-treatment ECG were included. ECGs were analyzed for heart rate, QT interval
      corrected using Bazett's formula (QTcB) and Fridericia's formula (QTcF), at
      screening and while being treated. PR, R-R, and QRS intervals and the maximum
      change in QTcB and QTcF from screening to endpoint were determined. Clinically
      significant thresholds were defined a priori. RESULTS: A total of 1,451 ECGs from
      449 patients receiving placebo (n = 207), paroxetine (n = 200), or imipramine (n
      = 42) were analyzed. Treatment with paroxetine did not significantly increase
      QTcB or QTcF or any ECG parameters compared with placebo. Treatment with
      imipramine significantly increased heart rate and QTcB, R-R, and QRS intervals
      compared with either paroxetine or placebo. CONCLUSIONS: Data from this
      retrospective study indicate that paroxetine (10-50 mg/day) is unlikely to be
      associated with significant ECG changes in medically healthy pediatric patients.

PMID- 16601648
TI  - Risperidone and adaptive behavior in children with autism.
AB  - OBJECTIVE: To evaluate the impact of risperidone on adaptive behavior in children
      with autistic disorder who have serious behavior problems and to examine
      different methods of scoring the Vineland Adaptive Behavior Scales to measure
      change. METHOD: Forty-eight children (5 years to 16 years, 5 months) who showed
      behavioral improvement during acute treatment with risperidone were followed for
      6 months and assessed with the Vineland Scales. RESULTS: Raw scores, age
      equivalents, and special norm percentile scores all showed significant increases
      in adaptive behavior in the areas of communication, daily living skills, and
      socialization (p <.01). During a period of 6 to 8 months, children gained an
      average of 7.8 age-equivalent months in the area of socialization, a > 6%
      improvement beyond what would be expected based on baseline growth rates.
      CONCLUSIONS: Although limited by the absence of a control group, these results
      suggest that risperidone may improve adaptive skills in children with autistic
      disorder accompanied by serious behavioral problems. Vineland age-equivalent
      scores appear to be most useful in assessing change with treatment over time.

PMID- 16601649
TI  - Attachment and externalizing disorders: a developmental psychopathology
      perspective.
AB  - OBJECTIVE: Attachment theory offers an intriguing formulation of protection and
      risk that ties together key aspects of behavior, emotion, and cognition. The
      authors present links among attachment status, other developmental domains, and
      the development and maintenance of externalizing disorders to illustrate an
      approach to integrating attachment theory and relationship research with the
      study of externalizing symptoms. METHOD: The authors review the literature on the
      attachment system's theoretical and empirical associations with domains of
      emotion regulation, social attributions, socialization and moral development, and
      intergenerational transmission of behavior, as well as with externalizing
      behaviors. RESULTS: There are a number of risk and protective connections between
      attachment security and other developmental processes that are associated with
      externalizing disorders. CONCLUSIONS: Knowledge of relational processes, in this
      case, attachment relationships, can contribute to an understanding of etiology,
      maintenance, and treatment of externalizing disorders.

PMID- 16601650
TI  - Family discord, parental depression, and psychopathology in offspring: 20-year
      follow-up.
AB  - OBJECTIVE: To determine the independent effects of parental depression and family
      discord on offspring psychopathology among children at high and low risk of
      depression. METHOD: Family discord factors were assessed when subjects were
      approximately 17 years old, and offspring diagnoses were assessed about 20 years
      later. Parental and offspring psychopathology was assessed by interviewers blind
      to parents' clinical status. The following dimensions of family discord were
      assessed: poor marital adjustment, parent child discord, low family cohesion,
      affectionless control, and parental divorce. RESULTS: Most family discord factors
      were associated with parental depression. Among children of depressed parents,
      none of the measures of family discord had a statistically significant
      association with offspring major depressive disorder or anxiety disorders. Among
      children of nondepressed parents, parental affectionless control was associated
      with an almost fivefold increased risk of major depressive disorder (odds ratio
      [OR] = 4.8; p < or = .05) and with more than a 14-fold increased risk of
      substance use disorders (OR = 14.3; p < or = .01). CONCLUSIONS: Parental
      depression is associated with family discord and is a consistent risk factor for
      offspring major depressive disorder and anxiety disorders, as shown over a 20
      year follow-up of offspring of depressed and nondepressed parents. Family discord
      factors may be a risk factor for major depressive disorder and substance use
      disorders in offspring of nondepressed parents.

PMID- 16601651
TI  - Is prenatal smoking associated with a developmental pattern of conduct problems
      in young boys?
AB  - OBJECTIVE: Prenatal smoking is robustly associated with increased risk of conduct
      problems in offspring. Observational studies that provide detailed phenotypic
      description are critical for generating testable hypotheses about underlying
      processes through which the effects of prenatal smoking may operate. To this end,
      we use a developmental framework to examine the association of exposure with (1)
      oppositional defiant disorder and attention-deficit/hyperactivity disorder in
      young boys and (2) the pattern of delinquent behavior at adolescence. METHOD:
      Using diagnostic measures and repeated measures of delinquency, we compare
      exposed and nonexposed boys from the youngest cohort of the Pittsburgh Youth
      Study (N = 448). RESULTS: Exposed boys were significantly more likely to (1)
      develop oppositional defiant disorder and comorbid oppositional defiant disorder
      attention-deficit/hyperactivity disorder but not attention-deficit/hyperactivity
      disorder alone and (2) to have an earlier onset of significant delinquent
      behavior. CONCLUSIONS: The early emergence and developmental coherence of
      exposure-related conduct problems is striking and is consistent with a behavioral
      teratological model. Phenotypically, exposure-related conduct problems appear to
      be characterized by socially resistant and impulsively aggressive behavior.
      Whether prenatal smoking plays an etiological role in or is a risk marker for the
      development of conduct problems, exposed offspring are at increased risk of an
      early-starter pathway to conduct problems.

PMID- 16601652
TI  - Poor response inhibition as a predictor of problem drinking and illicit drug use
      in adolescents at risk for alcoholism and other substance use disorders.
AB  - OBJECTIVE: To evaluate the predictive power of executive functions, in
      particular, response inhibition, in relation to alcohol-related problems and
      illicit drug use in adolescence. METHOD: A total of 498 children from 275
      families from a longitudinal high-risk study completed executive function
      measures in early and late adolescence and lifetime drinking and drug-related
      ratings at multiple time points including late adolescence (ages 15-17). Multi
      informant measures of attention-deficit/hyperactivity disorder and conduct
      disorder were obtained in early childhood (ages 3-5), middle childhood, and
      adolescence. RESULTS: In multilevel models, poor response inhibition predicted
      aggregate alcohol-related problems, the number of illicit drugs used, and
      comorbid alcohol and drug use (but not the number of drug-related problems),
      independently of IQ, parental alcoholism and antisocial personality disorder,
      child attention-deficit/hyperactivity disorder and conduct symptoms, or age.
      Multivariate models explained 8% to 20% of residual variance in outcome scores.
      The incremental predictive power of response inhibition was modest, explaining
      about 1% of the variance in most outcomes, but more than 9% of the residual
      variance in problem outcomes within the highest risk families. Other measured
      executive functions did not independently predict substance use onset.
      CONCLUSION: Models of alcoholism and other drug risks that invoke executive
      functions may benefit from specifying response inhibition as an incremental
      component.

PMID- 16601653
TI  - Different treatment thresholds in non-Western children with behavioral problems.
AB  - OBJECTIVE: First, to investigate whether non-Western children in the Netherlands
      are less likely to be treated for behavioral problems than Western children;
      second, to examine whether discrepancies in treatment status are related to
      differences in level of problem behavior and impairment. METHOD: The study
      included 2,185 children of the four largest ethnic groups in the Netherlands,
      namely, 684 Dutch, 702 Moroccan, 434 Turkish, and 365 Surinamese children from
      grades three to five of elementary school. Teachers completed the Strengths and
      Difficulties Questionnaire and five DSM-IV items on externalizing problems. In
      addition, they provided information on the treatment status of the child.
      RESULTS: Moroccan boys displayed more problem behavior, Turkish boys less problem
      behavior, and Surinamese boys similar rates of problem behavior compared with
      Dutch boys. No difference in problem behavior was found between Western and non
      Western girls. Adjusted for age, level of problem behavior, and impairment,
      Moroccan and Turkish children and Surinamese girls were less likely to receive
      treatment for problem behavior. CONCLUSIONS: The higher treatment thresholds of
      non-Western children compared with Western children in the Netherlands could not
      be explained by differences in level of problem behavior or impairment. Detection
      of behavioral problems in non-Western children should receive more attention.

PMID- 16601654
TI  - Telepsychiatry for treating rural American Indian youth.

PMID- 16601655
TI  - An evidence-based approach to an adolescent with emotional and behavioral
      dysregulation.

PMID- 16601656
TI  - Prediction of costs, effectiveness, and disease control of a population-based
      program using home sampling for diagnosis of urogenital Chlamydia trachomatis
      Infections.
AB  - OBJECTIVE: To estimate the incremental effects and costs of a home sampling
      screening approach for Chlamydia trachomatis over the current in-office screening
      practice in Denmark. GOALS: To assess the effect of a new screening strategy.
      STUDY DESIGN: A dynamic Monte Carlo model estimated prevalence and incidence over
      10 years for a home sampling screening program and the current in-office
      screening. Subsequently, the incremental number of major outcomes averted (MOA)
      and the related direct and indirect costs were estimated. RESULTS: Infection
      prevalence after 10 years was 1.0% with a home sampling program and 4.2% with the
      current in-office screening practice. The total costs per MOA reached 3186 US
      dollars during the first year of the home sampling strategy, but in year 4, the
      accumulated indirect costs offset the direct costs, and the program henceforth
      saved society costs. CONCLUSIONS: Home sampling should be considered a relevant
      alternative to the current practice of in-office screening.

PMID- 16601657
TI  - Herpes virus type 2 infection and genital symptoms in primary care patients.
AB  - OBJECTIVE: We aimed to identify whether genital symptoms were associated with
      unrecognized herpes simplex virus type 2 (HSV-2) infection in a primary care
      population. STUDY DESIGN: Five thousand four hundred fifty-two individuals aged
      18 to 59 seeking general care at 36 suburban medical offices in 6 U.S. cities
      were tested for HSV-2 antibody and asked about 10 types of genital symptoms. In
      patients with no known history of genital herpes, we assessed whether HSV-2
      infection was independently associated with symptoms. RESULTS: HSV-2 infection
      was associated with increases in reports of "sores, blisters, ulcers, crusts, or
      small cuts/slits" in men [adjusted odds ratio (OR), 1.79; 95% CI, 1.24-2.58] and
      with increases in reports of "redness, irritation, or a rash" among women
      (adjusted OR, 1.50; 95% CI, 1.06-2.11). HSV-2 was not significantly associated
      with other types of genital symptoms. CONCLUSIONS: Primary-care physicians should
      consider unrecognized HSV-2 infection as a potential cause of some common genital
      symptoms.

PMID- 16601658
TI  - Prevalence and correlates of human immunodeficiency virus infection among female
      sex workers in Tashkent, Uzbekistan.
AB  - OBJECTIVES/GOAL: To assess prevalence of and correlates to human immunodeficiency
      virus (HIV) infection among female sex workers in Tashkent, Uzbekistan. STUDY
      DESIGN: Women participating in this cross-sectional study completed a
      questionnaire and HIV testing between April 2003 and March 2004. Logistic
      regression analyses determined correlation of variables to HIV infection.
      RESULTS: Of 448 women, 10% (45) were HIV infected, which was associated with ever
      injecting drugs (AOR = 20.20; 95% confidence interval [CI], 7.69-53.07), street
      based sex work (AOR = 4.52; 95% CI, 1.84-11.12), exchanging sex for drugs (AOR =
      4.74; 95% CI, 1.84-12.18), and more sexually transmitted infection treatments in
      the preceding 3 months (AOR = 2.43; 95% CI, 1.14-5.17). CONCLUSIONS: Although
      injection drug use is the strongest correlate to HIV infection, sexual risk
      behaviors are independently related and should receive focus in prevention
      efforts targeted to this population.

PMID- 16601660
TI  - Identifying likely syphilis transmitters: implications for control and
      evaluation.
AB  - BACKGROUND/OBJECTIVES: Persistence of syphilis in communities may be maintained
      by relatively small groups of high-risk persons centrally placed among a larger
      group with low to moderately risky behavior. We sought to determine which control
      strategies identified particularly high-risk, early-stage syphilis cases
      considered to have high prevention value. METHODS: In 2 cities with recent
      heterosexual outbreaks, data were abstracted for early syphilis cases from 1997
      through 2002. Disease stage and number of sex partners were used to create an
      index to estimate the relative likelihood and magnitude of future transmission
      had the case not been treated. We estimated the relative transmission potential
      for each stage of syphilis (primary = 4.3, secondary = 2.5, and early-latent =
      1.0) and multiplied by the number of reported partners to determine a prevention
      value score. Cases scoring >10 were considered high prevention value. Cases were
      stratified by the method used to detect the case. RESULTS: Of 1,700 female early
      syphilis cases, 174 (10%) were high value. Cases were identified by private
      physicians (28% of all female cases and 16% of high-value cases), jails (19% of
      all, 40% of high-value cases), partner notification (16% of all, 10% of high
      value cases), sexually transmitted disease (STD) clinic (9% of all, 13% of high
      value cases), and the emergency room (8% of all, 4% of high-value cases). Of
      1,851 male cases, 228 (12%) were high value. Cases were identified by jails (27%
      of all male cases and 14% of high-value cases), STD clinic (21% of all, 47% of
      high-value), private physicians (17% of all, 17% of high-value), partner
      notification (14% of all, 11% of high-value), and the emergency room (6% of all,
      14% of high-value). CONCLUSIONS: Private physicians identified the most female
      cases; however, jail screening identified the most high-prevention-value female
      cases. Jail screening identified the most male cases; however, the STD clinic
      (self-referred) identified the most high-prevention-value cases. Partner
      notification identified relatively few high-value cases.

PMID- 16601659
TI  - Correlates of syphilis seroreactivity among pregnant women: the HIVNET 024 Trial
      in Malawi, Tanzania, and Zambia.
AB  - OBJECTIVES: The objectives of this cross-sectional study were to determine
      correlates of syphilis seroprevalence among HIV-infected and -uninfected
      antenatal attendees in an African multisite clinical trial, and to improve
      strategies for maternal syphilis prevention. RESULTS: A total of 2,270 (86%)
      women were HIV-infected and 366 (14%) were HIV-uninfected. One hundred seventy
      five (6.6%) were syphilis-seropositive (7.3% among HIV-infected and 2.6% HIV
      uninfected women). Statistically significant correlates included geographic site
      (odds ratio [OR] = 4.5, Blantyre; OR = 3.2, Lilongwe; OR = 9.0, Lusaka vs. Dar es
      Salaam referent); HIV infection (OR = 3.3); age 20 to 24 years (OR = 2.5); being
      divorced, widowed, or separated (OR = 2.9); genital ulcer treatment in the last
      year (OR = 2.9); history of stillbirth (OR = 2.8, one stillbirth; OR = 4.3, 2-5
      stillbirths); and history of preterm delivery (OR = 2.7, one preterm delivery).
      CONCLUSION: Many women without identified risk factors were syphilis
      seropositive. Younger HIV-infected women were at highest risk. Universal
      integrated antenatal HIV and syphilis screening and treatment is essential in sub
      Saharan African settings.

PMID- 16601661
TI  - Fluoroquinolone-resistant Neisseria gonorrhoeae in Bali, Indonesia: 2004.
AB  - OBJECTIVES: In the mid-1990s, fluoroquinolones were introduced in Indonesia for
      the management of gonorrhea and are now part of the national recommended
      treatment guidelines. We recently documented introduction of ciprofloxacin
      resistant Neisseria gonorrhoeae strains in female sex workers (FSWs) in Timika,
      Indonesia, 5 years after treating gonococcal cervicitis with ciprofloxacin and
      periodically monitoring antimicrobial susceptibility of isolates. To assess the
      importance of this observation, we determined antimicrobial susceptibilities and
      strain types of N. gonorrhoeae isolates from FSWs seen in a sexually transmitted
      infection (STI) clinic in Denpasar, Bali, Indonesia. GOAL: The goal of this study
      was to determine antimicrobial susceptibilities and strain types among N.
      gonorrhoeae isolated from FSWs in Denpasar, Bali. STUDY DESIGN: FSWs in Denpasar
      were screened for N. gonorrhoeae by standard culture. Endocervical isolates were
      frozen in Microbank tubes and sent to the University of California at San
      Francisco on dry ice. Antimicrobial susceptibility testing using a Clinical
      Laboratory Standards Institute-recommended agar dilution method was performed at
      the Centers for Disease Control and Prevention. Isolates were characterized by
      beta-lactamase production, antimicrobial resistance phenotypes, and
      auxotype/serovar class. RESULTS: One hundred forty-seven N. gonorrhoeae isolates
      were characterized. All isolates were highly resistant to tetracycline (minimum
      inhibitory concentration, >or=16.0 microg/mL): 117 (79.1%) were beta-lactamase
      positive (PP-TR), 3 (2.0%) exhibited chromosomally mediated resistance to
      penicillin (PenR-TRNG), and 27 (18.2%) were susceptible to penicillin (TRNG). All
      isolates were susceptible to ceftriaxone, cefixime, and spectinomycin; lack of
      interpretive criteria do not allow interpretation of susceptibilities of
      cefoxitin, cefpodoxime, or azithromycin. Fifty-nine (40.1%) isolates were
      ciprofloxacin-resistant; 35 (59.3%) of the ciprofloxacin-resistant isolates
      exhibited high-level resistance to ciprofloxacin (Cip-HLR; minimum inhibitory
      concentration, >or=4.0 microg/mL of ciprofloxacin). Three (2.0%) isolates were
      intermediate to ciprofloxacin. Twenty-two strain types were identified among
      these isolates; small clusters were identified with 3 strain types. CONCLUSIONS:
      N. gonorrhoeae isolates from FSWs in Denpasar were resistant to penicillin and
      tetracycline; 40.1% of the isolates were fluoroquinolone-resistant. With
      gonorrhea prevalence of 35% at this clinic (by nucleic acid amplified tests),
      ongoing surveillance for antimicrobial resistance will be needed to appropriately
      choose treatment for infections caused by these resistant organisms.

PMID- 16601662
TI  - Prevalence of Gardnerella vaginalis and Atopobium vaginae in virginal women.
AB  - OBJECTIVES: The objectives of this study was to determine the prevalence of
      Gardnerella vaginalis and Atopobium vaginae in virginal women and to establish if
      nonpenetrative sexual activity is associated with these organisms. GOAL: The goal
      of this study was to assess prevalence of G. vaginalis and A. vaginae in virginal
      women. STUDY DESIGN: Forty-four virginal female patients self-collected tampon
      specimens, which were tested for G. vaginalis and A. vaginae by polymerase chain
      reaction, and provided either brief or detailed information regarding sexual
      practices by self-administered questionnaire. RESULTS: Twenty women (45%) had G.
      vaginalis and 3 (7%) A. vaginae detected. Among the 27 who provided detailed
      information, 12 (46%) had G. vaginalis and none had A. vaginae detected. G.
      vaginalis was significantly more likely to be detected in those who had
      participated in oral sex (odds ratio = 22; 95% confidence interval = 2.2-222) and
      hand-genital contact without penetration (P = 0.02), but not genital-genital
      contact. CONCLUSION: This study shows that nonpenetrative intimate sexual contact
      is associated with carriage of G. vaginalis in virginal women.

PMID- 16601663
TI  - Homicides among children and young adults--Puerto Rico, 1999-2003.
AB  - Interpersonal violence causes substantial morbidity and mortality worldwide and
      poses a considerable economic burden, equivalent to 4%-5% of the gross national
      product in certain countries. The Commonwealth of Puerto Rico is a U.S. territory
      with a 2004 population of approximately 3.9 million. In Puerto Rico, homicides
      were the 12th leading cause of death overall in 2003, ranking fifth among males
      and 15th among females. This report summarizes an analysis of death certificate
      data on violent deaths of children and young adults in Puerto Rico during 1999
      2003, which determined that 93% of homicide victims aged <30 years were young
      males, the most common method of homicide was assault by firearm discharge, and
      the rate of homicide among males aged 25-29 years increased during the period. To
      address this problem, the Puerto Rican government has initiated a comprehensive
      strategy that includes enhancing an integrated surveillance system for fatal and
      nonfatal assault, supporting research on interpersonal violence, and establishing
      local prevention programs (e.g., violence prevention curricula in selected
      schools).

PMID- 16601664
TI  - Update: Guillain-Barre syndrome among recipients of Menactra meningococcal
      conjugate vaccine--United States, October 2005-February 2006.
AB  - In October 2005, a possible association between Guillain-Barre Syndrome (GBS) and
      receipt of meningococcal conjugate vaccine (i.e., meningococcal polysaccharide
      diphtheria toxoid conjugate vaccine [Menactra]) (MCV4) was reported. GBS is a
      serious neurologic disorder involving inflammatory demyelination of the
      peripheral nerves. At the time of the first report, five confirmed cases of GBS
      after receipt of MCV4 had been reported to the Vaccine Adverse Events Reporting
      System (VAERS). During the 4 months since, three additional confirmed cases of
      GBS have been reported. This report describes two of these recent cases and
      provides additional data collected through February 2006. Because available
      evidence neither proves nor disproves a causal relation between MCV4 and GBS,
      further monitoring and studies are ongoing within VAERS and the Vaccine Safety
      Datalink (VSD). CDC continues to recommend use of MCV4 for persons for whom
      vaccination is indicated; the additional reported cases have not resulted in any
      change to that recommendation.

PMID- 16601665
TI  - Mumps epidemic--Iowa, 2006.
AB  - In the United States, since 2001, an average of 265 mumps cases (range: 231-293
      cases) have been reported each year, and in Iowa, an average of five cases have
      been reported annually since 1996. However, in 2006, by March 28, a total of 219
      mumps cases had been reported in Iowa, and an additional 14 persons with
      clinically compatible symptoms were being investigated in three neighboring
      states (11 in Illinois, two in Nebraska, and one in Minnesota) in what has become
      the largest epidemic of mumps in the United States since 1988. This report
      summarizes and characterizes the ongoing mumps epidemic in Iowa, the public
      health response, and recommendations for preventing further transmission.

PMID- 16601666
TI  - Update: influenza activity--United States, March 19-25, 2006.
AB  - During March 19-25, 2006, the number of states reporting widespread influenza
      activity decreased to 16. Sixteen states reported regional activity, 13 reported
      local activity, and five reported sporadic activity.

PMID- 16601667
TI  - Surveillance for World Trade Center disaster health effects among survivors of
      collapsed and damaged buildings.
AB  - PROBLEM/CONDITION: Survivors of collapsed or damaged buildings from the attack on
      the World Trade Center (WTC) were among those most exposed to injury hazards, air
      pollution, and traumatic events. REPORTING PERIOD: This report summarizes data
      from health outcomes collected during interviews conducted from September 5,
      2003, to the close of the World Trade Center Health Registry (WTCHR) enrollment
      on November 20, 2004. DESCRIPTION OF SYSTEM: WTCHR will be used to monitor
      periodically the mental and physical health of 71,437 enrollees for 20 years. The
      analysis is limited to 8,418 adult survivors of collapsed buildings (n = 5,095)
      and buildings with major or moderate damage (n = 3,323), excluding those who were
      involved in rescue and recovery. RESULTS: A total of 62.4% of survivors of
      collapsed or damaged buildings were caught in the dust and debris cloud that
      resulted from the collapse of the WTC towers, and 63.8% experienced three or more
      potentially psychologically traumatizing events. Injuries were common (43.6%),
      but few survivors reported injuries that would have required extensive treatment.
      More than half (56.6%) of survivors reported experiencing new or worsening
      respiratory symptoms after the attacks, 23.9% had heartburn/reflux, and 21.0% had
      severe headaches. At the time of the interview, 10.7% of building survivors
      screened positive for serious psychological distress (SPD) using the K6
      instrument. After multiple adjustments, data indicated that survivors caught in
      the dust and debris cloud were more likely to report any injuries (adjusted odds
      ratio [AOR] = 3.9; p< or =0.05); any respiratory symptom (AOR = 2.7; p< or
      =0.05); severe headaches (AOR = 2.0; p< or =0.05); skin rash/irritation (AOR =
      1.7; p< or =0.05); hearing problems or loss (AOR = 1.7; p< or =0.05); heartburn
      (AOR = 1.7; p< or =0.05); diagnosed stroke (AOR = 5.6; p< or =0.05); self
      reported depression, anxiety, or other emotional problem (AOR = 1.4; p< or
      =0.05); and current SPD (AOR = 2.2; p< or =0.05). Adjustment for SPD did not
      diminish the observed associations between dust cloud exposure and physical
      health outcomes. Building type and time of evacuation were associated with
      injuries on September 11, 2001 and reported symptoms; building type (collapsed
      versus damaged) also was associated with mental distress. INTERPRETATION: Two to
      three years after September 11, survivors of buildings that collapsed or that
      were damaged as a result of the WTC attack reported substantial physical and
      mental health problems. The long-term ramifications of these effects are unknown.
      Many survivors were caught directly in the dust and debris of collapsing towers,
      a dense cloud of particulate matter that might have produced or exacerbated these
      health effects. PUBLIC HEALTH ACTION RECOMMENDED: Long-term follow-up of building
      survivors and all other persons enrolled in WTCHR should be maintained, with
      particular attention to those persons exposed to the dust cloud. Some of these
      findings might lead to building designs that can minimize injury hazards.

PMID- 16601668
TI  - Epidermolysis bullosa simplex with mottled pigmentation resulting from a
      recurrent mutation in KRT14.

PMID- 16601669
TI  - Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in
      a low-risk southern European population.
AB  - Individuals with melanocortin 1 receptor (MC1R) gene variants have been shown to
      carry an increased risk for the development of melanoma. In this study, we
      investigated the relationship of MC1R gene variants and the risk of melanoma in
      123 melanoma patients and 155 control subjects from Greece. The entire MC1R gene
      was sequenced for polymorphisms and the results were correlated with host factors
      and pigmentary characteristics. MC1R polymorphisms were present in 59.4% of
      melanoma patients compared to 37.5% of controls, yielding an odds ratio (OR) of
      2.43 (95% confidence interval (CI) = 1.50-3.96, P < 0.001) for melanoma among
      MC1R carriers. The risk of melanoma was enhanced in individuals carrying multiple
      variant alleles (OR = 6.97; 95% CI = 1.86-26.12, P = 0.004). Only the Val60Leu,
      Arg142His, and Arg151Cys variants were significantly associated with melanoma
      risk. In stratified analysis, the risk of melanoma among MC1R carriers was not
      influenced by skin phototype, skin color, or hair color. No association was found
      between MC1R genotype and the age of onset of melanoma, the tumor location, or
      the tumor thickness. In conclusion, MC1R polymorphisms are a predisposing factor
      of melanoma in a southern European population with a relatively low incidence of
      the disease.

PMID- 16601670
TI  - Serine protease activity and residual LEKTI expression determine phenotype in
      Netherton syndrome.
AB  - Mutations in the SPINK5 gene encoding the serine protease (SP) inhibitor,
      lymphoepithelial-Kazal-type 5 inhibitor (LEKTI), cause Netherton syndrome (NS), a
      life-threatening disease, owing to proteolysis of the stratum corneum (SC). We
      assessed here the basis for phenotypic variations in nine patients with "mild",
      "moderate", and "severe" NS. The magnitude of SP activation correlated with both
      the barrier defect and clinical severity, and inversely with residual LEKTI
      expression. LEKTI co-localizes within the SC with kallikreins 5 and 7 and
      inhibits both SP. The permeability barrier abnormality in NS was further linked
      to SC thinning and proteolysis of two lipid hydrolases (beta-glucocerebrosidase
      and acidic sphingomyelinase), with resultant disorganization of extracellular
      lamellar membranes. SC attenuation correlated with phenotype-dependent, SP
      activation, and loss of corneodesmosomes, owing to desmoglein (DSG)1 and
      desmocollin (DSC)1 degradation. Although excess SP activity extended into the
      nucleated layers in NS, degrading desmosomal mid-line structures with loss of
      DSG1/DSC1, the integrity of the nucleated epidermis appears to be maintained by
      compensatory upregulation of DSG3/DSC3. Maintenance of sufficient permeability
      barrier function for survival correlated with a compensatory acceleration of
      lamellar body secretion, providing a partial permeability barrier in NS. These
      studies provide a mechanistic basis for phenotypic variations in NS, and describe
      compensatory mechanisms that permit survival of NS patients in the face of
      unrelenting SP attack.

PMID- 16601671
TI  - Photoadaptation during narrowband ultraviolet-B therapy is independent of skin
      type: a study of 352 patients.
AB  - Understanding how photoadaptation differs between individuals is important when
      considering susceptibility to the beneficial and harmful effects of sunlight
      exposure and when determining optimal phototherapy regimens. Most narrowband UVB
      (NB-UVB) regimens start with 70% of the minimal erythema dose (MED) with 20%
      increments at each treatment thereafter. We retrospectively studied 352 skin
      types I-IV psoriatic patients having twice weekly treatment with this regimen.
      Patients with high skin types tended to have high MEDs (P<0.001). By session 20
      the proportion of patients who had developed erythema was approximately 60%
      regardless of MED. Among patients who developed erythema, the number of
      treatments before erythema occurred did not differ between skin types (P=0.33).
      We conclude that patients with high skin types photoadapt approximately equally
      per physical unit of UVR in comparison to those with low skin types, but they
      have greater photoadaptation in absolute terms because they are able to tolerate
      a higher initial dose of radiation. Differences in skin type or MED are not
      associated with clinically important differences in tendency to erythema during a
      standard 70/20% NB-UVB twice-weekly regimen. This regimen is suitable for all
      skin types I-IV patients regardless of skin type or MED.

PMID- 16601672
TI  - Ellagic and tannic acids protect newly synthesized elastic fibers from premature
      enzymatic degradation in dermal fibroblast cultures.
AB  - Progressive proteolytic degradation of cutaneous elastic fibers, that cannot be
      adequately replaced or repaired by adult dermal fibroblasts, constitutes a major
      feature of aging skin. Our present investigations, employing monolayer cultures
      of human dermal fibroblasts and organ cultures of skin biopsies, were aimed at
      testing whether the hydrophilic tannic acid (TA) and lipophilic ellagic acid (EA)
      would protect dermal elastin from exogenous and endogenous enzymatic degradation.
      Results from both culture systems indicated that dermal fibroblasts, maintained
      with TA or EA, deposit significantly more elastic fibers than untreated control
      cultures despite the fact that neither polyphenol enhanced transcription of
      elastin mRNA or cellular proliferation. Results of a pulse and chase experiment
      showed that pretreatment with both polyphenols enhanced biostability of
      tropoelastin and newly deposited elastin. Results of in vitro assays indicated
      that both polyphenols bound to purified elastin and significantly decreased its
      proteolytic degradation by elastolytic enzymes belonging to the serine
      proteinase, cysteine proteinase, and metallo-proteinase families. Importantly,
      both polyphenols also synergistically enhanced elastogenesis induced by selected
      elastogenic compounds in cultures of dermal fibroblasts. We propose that EA and
      TA may be useful for preventing proteolytic degradation of existing dermal
      elastic fibers and for enhancing more efficient elastogenesis in aged skin.

PMID- 16601673
TI  - TRPM2 activation by cyclic ADP-ribose at body temperature is involved in insulin
      secretion.
AB  - There are eight thermosensitive TRP (transient receptor potential) channels in
      mammals, and there might be other TRP channels sensitive to temperature stimuli.
      Here, we demonstrate that TRPM2 can be activated by exposure to warm temperatures
      (>35 degrees C) apparently via direct heat-evoked channel gating. beta-NAD(+)- or
      ADP-ribose-evoked TRPM2 activity is robustly potentiated at elevated
      temperatures. We also show that, even though cyclic ADP-ribose (cADPR) does not
      activate TRPM2 at 25 degrees C, co-application of heat and intracellular cADPR
      dramatically potentiates TRPM2 activity. Heat and cADPR evoke similar responses
      in rat insulinoma RIN-5F cells, which express TRPM2 endogenously. In pancreatic
      islets, TRPM2 is coexpressed with insulin, and mild heating of these cells evokes
      increases in both cytosolic Ca(2+) and insulin release, which is K(ATP) channel
      independent and protein kinase A-mediated. Heat-evoked responses in both RIN-5F
      cells and pancreatic islets are significantly diminished by treatment with TRPM2
      specific siRNA. These results identify TRPM2 as a potential molecular target for
      cADPR, and suggest that TRPM2 regulates Ca(2+) entry into pancreatic beta-cells
      at body temperature depending on the production of cADPR-related molecules,
      thereby regulating insulin secretion.

PMID- 16601674
TI  - Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent
      macrophage migration.
AB  - Migration of activated macrophages is essential for resolution of acute
      inflammation and the initiation of adaptive immunity. Here, we show that
      efficient macrophage migration in inflammatory environment depends on Mac-1
      recognition of a binary complex consisting of fibrin within the provisional
      matrix and the protease tPA (tissue-type plasminogen activator). Subsequent
      neutralization of tPA by its inhibitor PAI-1 enhances binding of the integrin
      protease-inhibitor complex to the endocytic receptor LRP (lipoprotein receptor
      related protein), triggering a switch from cell adhesion to cell detachment.
      Genetic inactivation of Mac-1, tPA, PAI-1 or LRP but not the protease uPA
      abrogates macrophage migration. The defective macrophage migration in PAI-1
      deficient mice can be restored by wild-type but not by a mutant PAI-1 that does
      not interact with LRP. In vitro analysis shows that tPA promotes Mac-1-mediated
      adhesion, whereas PAI-1 and LRP facilitate its transition to cell retraction. Our
      results emphasize the importance of ordered transitions both temporally and
      spatially between individual steps of cell migration, and support a model where
      efficient migration of inflammatory macrophages depends on cooperation of three
      physiologically prominent systems (integrins, coagulation and fibrinolysis, and
      endocytosis).

PMID- 16601675
TI  - The closed structure of presequence protease PreP forms a unique 10,000
      Angstroms3 chamber for proteolysis.
AB  - Presequence protease PreP is a novel protease that degrades targeting peptides as
      well as other unstructured peptides in both mitochondria and chloroplasts. The
      first structure of PreP from Arabidopsis thaliana refined at 2.1 Angstroms
      resolution shows how the 995-residue polypeptide forms a unique proteolytic
      chamber of more than 10,000 Angstroms(3) in which the active site resides.
      Although there is no visible opening to the chamber, a peptide is bound to the
      active site. The closed conformation places previously unidentified residues from
      the C-terminal domain at the active site, separated by almost 800 residues in
      sequence to active site residues located in the N-terminal domain. Based on the
      structure, a novel mechanism for proteolysis is proposed involving hinge-bending
      motions that cause the protease to open and close in response to substrate
      binding. In support of this model, cysteine double mutants designed to keep the
      chamber covalently locked show no activity under oxidizing conditions. The manner
      in which substrates are processed inside the chamber is reminiscent of the
      proteasome; therefore, we refer to this protein as a peptidasome.

PMID- 16601676
TI  - Poly(A) binding protein (PABP) homeostasis is mediated by the stability of its
      inhibitor, Paip2.
AB  - The poly(A)-binding protein (PABP) is a unique translation initiation factor in
      that it binds to the mRNA 3' poly(A) tail and stimulates recruitment of the
      ribosome to the mRNA at the 5' end. PABP activity is tightly controlled by the
      PABP-interacting protein 2 (Paip2), which inhibits translation by displacing PABP
      from the mRNA. Here, we describe a close interplay between PABP and Paip2 protein
      levels in the cell. We demonstrate a mechanism for this co-regulation that
      involves an E3 ubiquitin ligase, EDD, which targets Paip2 for degradation. PABP
      depletion by RNA interference (RNAi) causes co-depletion of Paip2 protein without
      affecting Paip2 mRNA levels. Upon PABP knockdown, Paip2 interacts with EDD, which
      leads to Paip2 ubiquitination. Supporting a critical role for EDD in Paip2
      degradation, knockdown of EDD expression by siRNA leads to an increase in Paip2
      protein stability. Thus, we demonstrate that the turnover of Paip2 in the cell is
      mediated by EDD and is regulated by PABP. This mechanism serves as a homeostatic
      feedback to control the activity of PABP in cells.

PMID- 16601677
TI  - Regulation of actin dynamics by annexin 2.
AB  - Annexin 2 is a ubiquitous Ca(2+)-binding protein that is essential for actin
      dependent vesicle transport. Here, we show that in spontaneously motile cells
      annexin 2 is concentrated in dynamic actin-rich protrusions, and that depletion
      of annexin 2 using siRNA leads to the accumulation of stress fibres and loss of
      protrusive and retractile activity. Cells co-expressing annexin 2-CFP and actin
      YFP exhibit Ca(2+)-dependent fluorescense resonance energy transfer throughout
      the cytoplasm and in membrane ruffles and protrusions, suggesting that annexin 2
      may directly interact with actin. This notion was supported by biochemical
      studies, in which we show that annexin 2 reduces the polymerisation rate of actin
      monomers in a dose-dependent manner. By measuring actin polymerisation rates in
      the presence of barbed-end and pointed-end cappers, we further demonstrate that
      annexin 2 specifically inhibits filament elongation at the barbed ends. These
      results show that annexin 2 has an essential role in maintaining the plasticity
      of the dynamic membrane-associated actin cytoskeleton, and that its activity in
      this context may be at least partly explained through direct interactions with
      polymerised and monomeric actin.

PMID- 16601678
TI  - Autoregulatory control of the p53 response by caspase-mediated processing of
      HIPK2.
AB  - The serine/threonine kinase HIPK2 phosphorylates the p53 protein at Ser 46, thus
      promoting p53-dependent gene expression and subsequent apoptosis. Here, we show
      that DNA damaging chemotherapeutic drugs cause degradation of endogenous HIPK2
      dependent on the presence of a functional p53 protein. Early induced p53 allows
      caspase-mediated cleavage of HIPK2 following aspartic acids 916 and 977. The
      resulting C-terminally truncated HIPK2 forms show an enhanced induction of the
      p53 response and cell death, thus allowing the rapid amplification of the p53
      dependent apoptotic program during the initiation phase of apoptosis by a
      regulatory feed-forward loop. The active HIPK2 fragments are further degraded
      during the execution and termination phase of apoptosis, thus ensuring the
      occurrence of HIPK2 signaling only during the early phases of apoptosis
      induction.

PMID- 16601679
TI  - Stepwise analyses of metal ions in RNase H catalysis from substrate
      destabilization to product release.
AB  - In two-metal catalysis, metal ion A has been proposed to activate the nucleophile
      and metal ion B to stabilize the transition state. We recently reported crystal
      structures of RNase H-RNA/DNA substrate complexes obtained at 1.5-2.2 Angstroms.
      We have now determined and report here structures of reaction intermediate and
      product complexes of RNase H at 1.65-1.85 Angstroms. The movement of the two
      metal ions suggests how they may facilitate RNA hydrolysis during the catalytic
      process. Firstly, metal ion A may assist nucleophilic attack by moving towards
      metal ion B and bringing the nucleophile close to the scissile phosphate.
      Secondly, metal ion B transforms from an irregular coordination in the substrate
      complex to a more regular geometry in the product complex. The exquisite
      sensitivity of Mg(2+) to the coordination environment likely destabilizes the
      enzyme-substrate complex and reduces the energy barrier to form product. Lastly,
      product release probably requires dissociation of metal ion A, which is inhibited
      by either high concentrations of divalent cations or mutation of an assisting
      protein residue.

PMID- 16601680
TI  - Requirement for SWI/SNF chromatin-remodeling complex in Tat-mediated activation
      of the HIV-1 promoter.
AB  - Activation of the human immunodeficiency virus type-1 (HIV-1) promoter in
      infected cells requires the sequential recruitment of several cellular factors to
      facilitate the formation of a processive elongation complex. The nucleosomal
      reorganization of the HIV-1 long terminal repeat (LTR) observed upon Tat
      stimulation suggests that chromatin-remodeling complexes could play a role during
      this process. Here, we reported that Tat interacts directly with Brm, a DNA
      dependent ATPase subunit of the SWI/SNF chromatin-remodeling complex, to activate
      the HIV-1 LTR. Inhibition of Brm via small interfering RNAs impaired Tat-mediated
      transactivation of an integrated HIV-1 promoter. Furthermore, Brm is recruited in
      vivo to the HIV-1 LTR in a Tat-dependent manner. Interestingly, we found that
      Tat/Brm interaction is regulated by Tat lysine 50 acetylation. These data show
      the requirement of Tat-mediated recruitment of SWI/SNF chromatin-remodeling
      complex to HIV-1 promoter in the activation of the LTR.

PMID- 16601681
TI  - Antiviral effect of the mammalian translation initiation factor 2alpha kinase
      GCN2 against RNA viruses.
AB  - In mammals, four different protein kinases, heme-regulated inhibitor, double
      stranded RNA-dependent protein kinase (PKR), general control non-derepressible-2
      (GCN2) and PKR-like endoplasmic reticulum kinase, regulate protein synthesis in
      response to environmental stresses by phosphorylating the alpha-subunit of the
      initiation factor 2 (eIF2alpha). We now report that mammalian GCN2 is
      specifically activated in vitro upon binding of two nonadjacent regions of the
      Sindbis virus (SV) genomic RNA to its histidyl-tRNA synthetase-related domain.
      Moreover, endogenous GCN2 is activated in cells upon SV infection. Strikingly,
      fibroblasts derived from GCN2-/- mice possess an increased permissiveness to SV
      or vesicular stomatitis virus infection. We further show that mice lacking GCN2
      are extremely susceptible to intranasal SV infection, demonstrating high virus
      titers in the brain compared to similarly infected control animals. The
      overexpression of wild-type GCN2, but not the catalytically inactive GCN2-K618R
      variant, in NIH 3T3 cells impaired the replication of a number of RNA viruses. We
      determined that GCN2 inhibits SV replication by blocking early viral translation
      of genomic SV RNA. These findings point to a hitherto unrecognized role of GCN2
      as an early mediator in the cellular response to RNA viruses.

PMID- 16601682
TI  - Cockayne syndrome B protein regulates the transcriptional program after UV
      irradiation.
AB  - The phenotype of the human genetic disorder Cockayne syndrome (CS) is not only
      due to DNA repair defect but also (and perhaps essentially) to a severe
      transcription initiation defect. After UV irradiation, even undamaged genes are
      not transcribed in CSB cells. Indeed, neither RNA pol II nor the associated basal
      transcription factors are recruited to the promoters of the housekeeping genes,
      around of which histone H4 acetylation is also deficient. Transfection of CSB
      restores the recruitment process of RNA pol II. On the contrary, the p53
      responsive genes do not require CSB and are transcribed in both wild-type and CSB
      cells upon DNA damage. Altogether, our data highlight the pivotal role of CSB in
      initiating the transcriptional program of certain genes after UV irradiation, and
      also may explain some of the complex traits of CS patients.

PMID- 16601683
TI  - Mba1, a membrane-associated ribosome receptor in mitochondria.
AB  - The genome of mitochondria encodes a small number of very hydrophobic
      polypeptides that are inserted into the inner membrane in a cotranslational
      reaction. The molecular process by which mitochondrial ribosomes are recruited to
      the membrane is poorly understood. Here, we show that the inner membrane protein
      Mba1 binds to the large subunit of mitochondrial ribosomes. It thereby cooperates
      with the C-terminal ribosome-binding domain of Oxa1, which is a central component
      of the insertion machinery of the inner membrane. In the absence of both Mba1 and
      the C-terminus of Oxa1, mitochondrial translation products fail to be properly
      inserted into the inner membrane and serve as substrates of the matrix chaperone
      Hsp70. We propose that Mba1 functions as a ribosome receptor that cooperates with
      Oxa1 in the positioning of the ribosome exit site to the insertion machinery of
      the inner membrane.

PMID- 16601684
TI  - The role of an upstream promoter interaction in initiation of bacterial
      transcription.
AB  - The bacterial RNA polymerase (RNAP) recognizes promoters through sequence
      specific contacts of its promoter-specificity components (sigma) with two DNA
      sequence motifs. Contacts with the upstream ('-35') promoter motif are made by
      sigma domain 4 attached to the flap domain of the RNAP beta subunit.
      Bacteriophage T4 late promoters consist solely of an extended downstream ('-10')
      motif specifically recognized by the T4 gene 55 protein (gp55). Low level basal
      transcription is sustained by gp55-RNAP holoenzyme. The late transcription
      coactivator gp33 binds to the beta flap and represses this basal transcription.
      Gp33 can also repress transcription by Escherichia coli sigma70-RNAP holoenzyme
      mutated to allow gp33 access to the beta flap. We propose that repression is due
      to gp33 blocking an upstream sequence-independent DNA-binding site on RNAP (as
      sigma70 domain 4 does) but, unlike sigma70 domain 4, providing no new DNA
      interaction. We show that this upstream interaction is essential only at an early
      step of transcription initiation, and discuss the role of this interaction in
      promoter recognition and transcriptional regulation.

PMID- 16601685
TI  - GGA function is required for maturation of neuroendocrine secretory granules.
AB  - Secretory granule (SG) maturation has been proposed to involve formation of
      clathrin-coated vesicles (CCVs) from immature SGs (ISGs). We tested the effect of
      inhibiting CCV budding by using the clathrin adaptor GGA (Golgi-associated, gamma
      ear-containing, ADP-ribosylation factor-binding protein) on SG maturation in
      neuroendocrine cells. Overexpression of a truncated, GFP-tagged GGA, VHS (Vps27,
      Hrs, Stam)-GAT (GGA and target of myb (TOM))-GFP led to retention of MPR, VAMP4,
      and syntaxin 6 in mature SGs (MSGs), suggesting that CCV budding from ISGs is
      inhibited by the SG-localizing VHS-GAT-GFP. Furthermore, VHS-GAT-GFP
      overexpression disrupts prohormone convertase 2 (PC2) autocatalytic cleavage,
      processing of secretogranin II to its product p18, and the correlation between
      PC2 and p18 levels. All these effects were not observed if full-length GGA1-GFP
      was overexpressed. Neither GGA1-GFP nor VHS-GAT-GFP perturbed SG protein budding
      from the TGN, or homotypic fusion of ISGs. Reducing GGA3 levels by using short
      interfering (si)RNA also led to VAMP4 retention in SGs, and inhibition of PC2
      activity. Our results suggest that inhibition of CCV budding from ISGs
      downregulates the sorting from the ISGs and perturbs the intragranular activity
      of PC2.

PMID- 16601686
TI  - Tip60 and p400 are both required for UV-induced apoptosis but play antagonistic
      roles in cell cycle progression.
AB  - The histone acetyl transferase Tip60 (HTATIP) belongs to a multimolecular complex
      involved in the cellular response to DNA damage. Tip60 participates in cell cycle
      arrest following DNA damage by allowing p53 to activate p21CIP (p21) expression.
      We show here that Tip60 and the E1A-associated p400 protein (EP400), which
      belongs to the Tip60 complex, are also required for DNA damage-induced apoptosis.
      Tip60 favours the expression of some proapoptotic p53 target genes most likely
      through the stimulation of p53 DNA binding activity. In contrast, p400 represses
      p21 expression in unstressed cells, thereby allowing cell cycle progression and
      DNA damage-induced apoptosis. Tip60 and p400 have thus opposite effects on p21
      expression in the absence of DNA damage. We further found that this antagonism
      relies on the inhibition of Tip60 function by p400, a property that is abolished
      following DNA damage. Therefore, taken together, our results indicate that Tip60
      and p400 play distinct roles in DNA damage-induced apoptosis and underline the
      importance of the Tip60 complex and its regulation in the proper control of cell
      fate.

PMID- 16601687
TI  - Dual role of the exocyst in AMPA receptor targeting and insertion into the
      postsynaptic membrane.
AB  - Intracellular membrane trafficking of glutamate receptors at excitatory synapses
      is critical for synaptic function. However, little is known about the specialized
      trafficking events occurring at the postsynaptic membrane. We have found that two
      components of the exocyst complex, Sec8 and Exo70, separately control synaptic
      targeting and insertion of AMPA-type glutamate receptors. Sec8 controls the
      directional movement of receptors towards synapses through PDZ-dependent
      interactions. In contrast, Exo70 mediates receptor insertion at the postsynaptic
      membrane, but it does not participate in receptor targeting. Thus, interference
      with Exo70 function accumulates AMPA receptors inside the spine, forming a
      complex physically associated, but not yet fused with the postsynaptic membrane.
      Electron microscopic analysis of these complexes indicates that Exo70 mediates
      AMPA receptor insertion directly within the postsynaptic density, rather than at
      extrasynaptic membranes. Therefore, we propose a molecular and anatomical model
      that dissects AMPA receptor sorting and synaptic delivery within the spine, and
      uncovers new functions of the exocyst at the postsynaptic membrane.

PMID- 16601688
TI  - The effects of mitochondrial iron homeostasis on cofactor specificity of
      superoxide dismutase 2.
AB  - Many metalloproteins have the capacity to bind diverse metals, but in living
      cells connect only with their cognate metal cofactor. In eukaryotes, this metal
      specificity can be achieved through metal-specific metallochaperone proteins.
      Herein, we describe a mechanism whereby Saccharomyces cerevisiae manganese
      superoxide dismutase (SOD2) preferentially binds manganese over iron based on the
      differential bioavailability of these ions within mitochondria. The bulk of
      mitochondrial iron is normally unavailable to SOD2, but when mitochondrial iron
      homeostasis is disrupted, for example, by mutations in S. cerevisiae mtm1, ssq1
      and grx5, iron accumulates in a reactive form that potently competes with
      manganese for binding to SOD2, inactivating the enzyme. Studies in mtm1 mutants
      indicate that iron inactivation of SOD2 involves the Mrs3p/Mrs4p mitochondrial
      carriers and iron-binding frataxin (Yfh1p). A small pool of SOD2-reactive iron
      also exists under normal iron homeostasis conditions and binds SOD2 when
      mitochondrial manganese is low. The ability to control this reactive pool of iron
      is critical to maintaining SOD2 activity and has important potential implications
      for oxidative stress in disorders of iron overload.

PMID- 16601690
TI  - Molecular determinants of polyubiquitin linkage selection by an HECT ubiquitin
      ligase.
AB  - Ubiquitin (Ub)-protein ligases (E3s) frequently modify their substrates with
      multiple Ub molecules in the form of a polyubiquitin (poly-Ub) chain. Although
      structurally distinct poly-Ub chains (linked through different Ub lysine (Lys)
      residues) can confer different fates on target proteins, little is known about
      how E3s select the Lys residue to be used in chain synthesis. Here, we used a
      combination of mutagenesis, biochemistry, and mass spectrometry to map
      determinants of linkage choice in chain assembly catalyzed by KIAA10, an HECT
      (Homologous to E6AP C-Terminus) domain E3 that synthesizes K29- and K48-linked
      chains. Focusing on the Ub molecule that contributes the Lys residue for chain
      formation, we found that specific surface residues adjacent to K48 and K29 are
      critical for the usage of the respective Lys residues in chain synthesis. This
      direct mechanism of linkage choice bears similarities to the mechanism of
      substrate site selection in sumoylation catalyzed by Ubc9, but is distinct from
      the mechanism of chain linkage selection used by the Mms2/Ubc13 (Ub E2 variant
      (UEV)/E2) complex.

PMID- 16601689
TI  - Distinct roles for Sld3 and GINS during establishment and progression of
      eukaryotic DNA replication forks.
AB  - The Cdc45 protein is crucial for the initiation of chromosome replication in
      eukaryotic cells, as it allows the activation of prereplication complexes (pre
      RCs) that contain the MCM helicase. This causes the unwinding of origins and the
      establishment of DNA replication forks. The incorporation of Cdc45 at nascent
      forks is a highly regulated and poorly understood process that requires, in
      budding yeast, the Sld3 protein and the GINS complex. Previous studies suggested
      that Sld3 is also important for the progression of DNA replication forks after
      the initiation step, as are Cdc45 and GINS. In contrast, we show here that Sld3
      does not move with DNA replication forks and only associates with MCM in an
      unstable manner before initiation. After the establishment of DNA replication
      forks from early origins, Sld3 is no longer essential for the completion of
      chromosome replication. Unlike Sld3, GINS is not required for the initial
      recruitment of Cdc45 to origins and instead is necessary for stable engagement of
      Cdc45 with the nascent replisome. Like Cdc45, GINS then associates stably with
      MCM during S-phase.

PMID- 16601691
TI  - Adaptability of myosin V studied by simultaneous detection of position and
      orientation.
AB  - We studied the structural dynamics of chicken myosin V by combining the
      localization power of fluorescent imaging with one nanometer accuracy (FIONA)
      with the ability to detect angular changes of a fluorescent probe. The myosin V
      was labeled with bifunctional rhodamine on one of its calmodulin light chains.
      For every 74 nm translocation, the probe exhibited two reorientational motions,
      associated with alternating smaller and larger translational steps. Molecules
      previously identified as stepping alternatively 74-0 nm were found to actually
      step 64-10 nm. Additional tilting often occurred without full steps, possibly
      indicating flexibility of the attached myosin heads or probing of their vicinity.
      Processive myosin V molecules sometimes shifted from the top to the side of
      actin, possibly to avoid an obstacle. The data indicate marked adaptability of
      this molecular motor to a nonuniform local environment and provide strong support
      for a straight-neck model of myosin V in which the lever arm of the leading head
      is tilted backwards at the prepowerstoke angle.

PMID- 16601692
TI  - Glycine-alanine repeats impair proper substrate unfolding by the proteasome.
AB  - Proteasome ATPases unravel folded proteins. Introducing a sequence containing
      only glycine and alanine residues (GAr) into substrates can impair their
      digestion. We previously proposed that a GAr interferes with the unfolding
      capacity of the proteasome, leading to partial degradation of products. Here we
      tested that idea in several ways. Stabilizing or destabilizing a folded domain
      within substrate proteins changed GAr-mediated intermediate production in the way
      predicted by the model. A downstream folded domain determined the sites of
      terminal proteolysis. The spacing between a GAr and a folded domain was critical
      for intermediate production. Intermediates containing a GAr did not remain
      associated with proteasomes, excluding models whereby retained GAr-containing
      proteins halt further processing. The following model is supported: a GAr
      positioned within the ATPase ring reduces the efficiency of coupling between
      nucleotide hydrolysis and work performed on the substrate. If this impairment
      takes place when unfolding must be initiated, insertion pauses and proteolysis is
      limited to the portion of the substrate that has already entered the catalytic
      chamber of the proteasome.

PMID- 16601693
TI  - Axin is a scaffold protein in TGF-beta signaling that promotes degradation of
      Smad7 by Arkadia.
AB  - TGF-beta signaling involves a wide array of signaling molecules and multiple
      controlling events. Scaffold proteins create a functional proximity of signaling
      molecules and control the specificity of signal transduction. While many
      components involved in the TGF-beta pathway have been elucidated, little is known
      about how those components are coordinated by scaffold proteins. Here, we show
      that Axin activates TGF-beta signaling by forming a multimeric complex consisting
      of Smad7 and ubiquitin E3 ligase Arkadia. Axin depends on Arkadia to facilitate
      TGF-beta signaling, as their small interfering RNAs reciprocally abolished the
      stimulatory effect on TGF-beta signaling. Specific knockdown of Axin or Arkadia
      revealed that Axin and Arkadia cooperate with each other in promoting Smad7
      ubiquitination. Pulse-chase experiments further illustrated that Axin
      significantly decreased the half-life of Smad7. Axin also induces nuclear export
      of Smad7. Interestingly, Axin associates with Arkadia and Smad7 independently of
      TGF-beta signal, in contrast to its transient association with inactive Smad3.
      However, coexpression of Wnt-1 reduced Smad7 ubiquitination by downregulating
      Axin levels, underscoring the importance of Axin as an intrinsic regulator in TGF
      beta signaling.

PMID- 16601694
TI  - Lysine-63-linked ubiquitination is required for endolysosomal degradation of
      class I molecules.
AB  - MHC class I molecules display peptides from endogenous and viral proteins for
      immunosurveillance by cytotoxic T lymphocytes (CTL). The importance of the class
      I pathway is emphasised by the remarkable strategies employed by different
      viruses to downregulate surface class I and avoid CTL recognition. The K3 gene
      product from Kaposi's sarcoma-associated herpesvirus (KSHV) is a viral ubiquitin
      E3 ligase which ubiquitinates and degrades cell surface MHC class I molecules. We
      now show that modification of K3-associated class I by lysine-63-linked
      polyubiquitin chains is necessary for their efficient endocytosis and
      endolysosomal degradation and present three lines of evidence that
      monoubiquitination of class I molecules provides an inefficient internalisation
      signal. This lysine-63-linked polyubiquitination requires both UbcH5b/c and Ubc13
      conjugating enzymes for initiating mono- and subsequent polyubiquitination of
      class I, and the clathrin-dependent internalisation is mediated by the epsin
      endocytic adaptor. Our results explain how lysine-63-linked polyubiquitination
      leads to degradation by an endolysosomal pathway and demonstrate a novel
      mechanism for endocytosis and endolysosomal degradation of class I, which may be
      applicable to other receptors.

PMID- 16601695
TI  - Conformational changes in the AAA ATPase p97-p47 adaptor complex.
AB  - The AAA+ATPase p97/VCP, helped by adaptor proteins, exerts its essential role in
      cellular events such as endoplasmic reticulum-associated protein degradation or
      the reassembly of Golgi, ER and the nuclear envelope after mitosis. Here, we
      report the three-dimensional cryo-electron microscopy structures at approximately
      20 Angstroms resolution in two nucleotide states of the endogenous hexameric p97
      in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins
      involved in membrane fusion. Depending on the nucleotide state, we observe the
      p47 trimer to be in two distinct arrangements on top of the p97 hexamer. By
      combining the EM data with NMR and other biophysical measurements, we propose a
      model of ATP-dependent p97(N) domain motions that lead to a rearrangement of p47
      domains, which could result in the disassembly of target protein complexes.

PMID- 16601696
TI  - Activation of the anaphase promoting complex by HTLV-1 tax leads to senescence.
AB  - The human T-lymphotropic virus type 1 (HTLV-1) Tax binds the anaphase promoting
      complex (APC) and activates it ahead of schedule. Here, we show that APC
      activation by Tax induces rapid senescence (tax-IRS) independently of p53 and
      pRB. In response to tax, cyclin A, cyclin B1, securin, and Skp2 becomes
      polyubiquitinated and degraded starting in S phase. This is followed by a surge
      in p21(CIP1/WAF1) and p27(KIP1) in mid to late S and G2/M leading to a permanent
      G1 arrest. Tax-positive HTLV-1-transformed T-cell lines express elevated levels
      of p21(CIP1/WAF1), but low levels of p27(KIP1). Finally, Tax can be stably
      expressed in p27(KIP1)-null NIH3T3 cells. These results indicate that APC
      activation by Tax causes inactivation of SCF(Skp2) and stabilization of
      p21(CIP1/WAF1) and p27(KIP1). The build-up of p21(CIP1/WAF1) and especially
      p27(KIP1) commits cells to senescence. Evading tax-IRS through a loss of
      p27(KIP1) function is likely to be critical for cell transformation by Tax and
      development of adult T-cell leukemia after HTLV-1 infection. Finally, activation
      of APC ahead of schedule may be exploited to arrest cancer cell growth.

PMID- 16601697
TI  - SH3P7/mAbp1 deficiency leads to tissue and behavioral abnormalities and impaired
      vesicle transport.
AB  - The intracellular adaptor protein SH3P7 is the mammalian ortholog of yeast actin
      binding protein 1 and thus alternatively named as mAbp1 (or HIP55). Structural
      properties, biochemical analysis of its interaction partners and siRNA studies
      implicated mAbp1 as an accessory protein in clathrin-mediated endocytosis (CME).
      Here, we describe the generation and characterization of mice deficient for
      SH3P7/mAbp1 owing to targeted gene disruption in embryonic stem cells. Mutant
      animals are viable and fertile without obvious deficits during the first weeks of
      life. Abnormal structure and function of organs including the spleen, heart, and
      lung is observed at about 3 months of age in both heterozygous and homozygous
      mouse mutants. A moderate reduction of both receptor-mediated and synaptic
      endocytosis is observed in embryonic fibroblasts and in synapses of hippocampal
      neurons, respectively. Recycling of synaptic vesicles in hippocampal boutons is
      severely impaired and delayed four-fold. The presynaptic defect of SH3P7/mAbp1
      mouse mutants is associated with their constricted physical capabilities and
      disturbed neuromotoric behaviour. Our data reveal a nonredundant role of
      SH3P7/mAbp1 in CME and places its function downstream of vesicle fission.

PMID- 16601698
TI  - Structure of complement factor H carboxyl-terminus reveals molecular basis of
      atypical haemolytic uremic syndrome.
AB  - Factor H (FH) is the key regulator of the alternative pathway of complement. The
      carboxyl-terminal domains 19-20 of FH interact with the major opsonin C3b,
      glycosaminoglycans, and endothelial cells. Mutations within this area are
      associated with atypical haemolytic uremic syndrome (aHUS), a disease
      characterized by damage to endothelial cells, erythrocytes, and kidney glomeruli.
      The structure of recombinant FH19-20, solved at 1.8 A by X-ray crystallography,
      reveals that the short consensus repeat domain 20 contains, unusually, a short
      alpha-helix, and a patch of basic residues at its base. Most aHUS-associated
      mutations either destabilize the structure or cluster in a unique region on the
      surface of FH20. This region is close to, but distinct from, the primary heparin
      binding patch of basic residues. By mutating five residues in this region, we
      show that it is involved, not in heparin, but in C3b binding. Therefore, the
      majority of the aHUS-associated mutations on the surface of FH19-20 interfere
      with the interaction between FH and C3b. This obviously leads to impaired control
      of complement attack on plasma-exposed cell surfaces in aHUS.

PMID- 16601699
TI  - Purification of active HOPS complex reveals its affinities for phosphoinositides
      and the SNARE Vam7p.
AB  - Coupling of Rab GTPase activation and SNARE complex assembly during membrane
      fusion is poorly understood. The homotypic fusion and vacuole protein sorting
      (HOPS) complex links these two processes: it is an effector for the vacuolar Rab
      GTPase Ypt7p and is required for vacuolar SNARE complex assembly. We now report
      that pure, active HOPS complex binds phosphoinositides and the PX domain of the
      vacuolar SNARE protein Vam7p. These binding interactions support HOPS complex
      association with the vacuole and explain its enrichment at the same microdomains
      on docked vacuoles as phosphoinositides, Ypt7p, Vam7p, and the other SNARE
      proteins. Concentration of the HOPS complex at these microdomains may be a key
      factor for coupling Rab GTPase activation to SNARE complex assembly.

PMID- 16601702
TI  - The end of the beginning?

PMID- 16601700
TI  - Nucleolin is a histone chaperone with FACT-like activity and assists remodeling
      of nucleosomes.
AB  - Remodeling machines play an essential role in the control of gene expression, but
      how their activity is regulated is not known. Here we report that the nuclear
      protein nucleolin possesses a histone chaperone activity and that this factor
      greatly enhances the activity of the chromatin remodeling machineries SWI/SNF and
      ACF. Interestingly, nucleolin is able to induce the remodeling by SWI/SNF of
      macroH2A, but not of H2ABbd nucleosomes, which are otherwise resistant to
      remodeling. This new histone chaperone promotes the destabilization of the
      histone octamer, helping the dissociation of a H2A-H2B dimer, and stimulates the
      SWI/SNF-mediated transfer of H2A-H2B dimers. Furthermore, nucleolin facilitates
      transcription through the nucleosome, which is reminiscent of the activity of the
      FACT complex. This work defines new functions for histone chaperones in chromatin
      remodeling and regulation of transcription and explains how nucleolin could act
      on transcription.

PMID- 16601701
TI  - ATM and ATR promote Mre11 dependent restart of collapsed replication forks and
      prevent accumulation of DNA breaks.
AB  - Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia Rad3-related (ATR) and
      the Mre11/Rad50/Nbs1 complex ensure genome stability in response to DNA damage.
      However, their essential role in DNA metabolism remains unknown. Here we show
      that ATM and ATR prevent accumulation of DNA double-strand breaks (DSBs) during
      chromosomal replication. Replicating chromosomes accumulate DSBs in Xenopus
      laevis egg extracts depleted of ATM and ATR. Addition of ATM and ATR proteins to
      depleted extracts prevents DSB accumulation by promoting restart of collapsed
      replication forks that arise during DNA replication. We show that collapsed forks
      maintain MCM complex but lose Pol epsilon, and that Pol epsilon reloading
      requires ATM and ATR. Replication fork restart is abolished in Mre11 depleted
      extracts and is restored by supplementation with recombinant human
      Mre11/Rad50/Nbs1 complex. Using a novel fluorescence resonance energy transfer
      based technique, we demonstrate that ATM and ATR induce Mre11/Rad50/Nbs1 complex
      redistribution to restarting forks. This study provides direct biochemical
      evidence that ATM and ATR prevent accumulation of chromosomal abnormalities by
      promoting Mre11/Rad50/Nbs1 dependent recovery of collapsed replication forks.

PMID- 16601703
TI  - Transgenic milk prospects turn sour.

PMID- 16601704
TI  - Consequences.

PMID- 16601705
TI  - First inhalable insulin approved.

PMID- 16601706
TI  - Complement inhibitors finally find orphan niches.

PMID- 16601707
TI  - Hedge funds gain edge by doubling biotech investments.

PMID- 16601708
TI  - China kickstarts its vaccine market.

PMID- 16601710
TI  - Agbiotech goes further afield.

PMID- 16601711
TI  - Trends in biotech literature 2005.

PMID- 16601712
TI  - BIO reaches adolescence.

PMID- 16601713
TI  - An international gap in human ES cell research.

PMID- 16601714
TI  - Are Europeans really antagonistic to biotech?

PMID- 16601715
TI  - Hwang's fraud adds impetus to ES cell research.

PMID- 16601716
TI  - Low-lignin wood--a case study.

PMID- 16601717
TI  - Can science resolve the ethical impasse in stem cell research?
AB  - Advances in our understanding of the control of early human embryonic development
      could offer solutions to the moral dilemmas associated with human embryonic stem
      cell research.

PMID- 16601718
TI  - My worst biotech investment.

PMID- 16601719
TI  - Putting pharmacogenetics into practice.
AB  - Genetics is slowly explaining variations in drug response, but applying this
      knowledge depends on implementation of a host of policies that provide long-term
      support to the field, from translational research and regulation to professional
      education.

PMID- 16601721
TI  - Recent patent applications in stem cell research.

PMID- 16601720
TI  - The paths around stem cell intellectual property.
AB  - Can new approaches for deriving human stem cells circumnavigate existing patents
      that dominate embryonic stem cell intellectual property?

PMID- 16601722
TI  - Ion-channel drug screening galvanized.

PMID- 16601723
TI  - A peptide chaperone for transdermal drug delivery.

PMID- 16601724
TI  - Breeding new life into plant metabolism.

PMID- 16601725
TI  - Do targets limit antibiotic discovery?

PMID- 16601727
TI  - What are DNA sequence motifs?
AB  - Sequence motifs are becoming increasingly important in the analysis of gene
      regulation. How do we define sequence motifs, and why should we use sequence
      logos instead of consensus sequences to represent them? Do they have any relation
      with binding affinity? How do we search for new instances of a motif in this sea
      of DNA?

PMID- 16601728
TI  - Modeling cellular machinery through biological network comparison.
AB  - Molecular networks represent the backbone of molecular activity within the cell.
      Recent studies have taken a comparative approach toward interpreting these
      networks, contrasting networks of different species and molecular types, and
      under varying conditions. In this review, we survey the field of comparative
      biological network analysis and describe its applications to elucidate cellular
      machinery and to predict protein function and interaction. We highlight the open
      problems in the field as well as propose some initial mathematical formulations
      for addressing them. Many of the methodological and conceptual advances that were
      important for sequence comparison will likely also be important at the network
      level, including improved search algorithms, techniques for multiple alignment,
      evolutionary models for similarity scoring and better integration with public
      databases.

PMID- 16601734
TI  - What are you worth?
AB  - Knowing the language of compensation is essential to negotiating the fair market
      value of your worth.

PMID- 16601736
TI  - Adalimumab for sight-threatening uveitis in Behcet's disease.
AB  - AIMS: To describe the clinical outcome of three patients with Behcet's disease
      maintained on infliximab who were switched to adalimumab therapy. METHODS: Case
      note review. Main outcome measure was recurrence of uveitis. RESULTS: All
      patients remained free of recurrence with stable visual acuities. CONCLUSIONS:
      Adalimumab appears to maintain disease remission in Behcet's disease.

PMID- 16601737
TI  - Diurnal intraocular pressure profiles and progression of chronic open-angle
      glaucoma.
AB  - PURPOSE: To evaluate whether the amplitude of day-and-night intraocular pressure
      (IOP) profiles influences the rate of progression of chronic open-angle glaucoma.
      METHODS: The hospital-based clinical observational study included day-and-night
      profiles of IOP measurements performed on 458 patients (855 eyes) with chronic
      open-angle glaucoma or ocular hypertension. The 24-h pressure profiles obtained
      by Goldmann applanation tonometry contained measurements at 0700, noon, 1700,
      2100, and midnight. RESULTS: In the whole study population, IOP amplitude was
      significantly (P<0.001) and positively associated with the mean (r=0.26), minimal
      (r=-0.23) and maximal (r=0.59) IOP values. Taking the whole study population,
      glaucoma progression was not associated with the IOP amplitude (P=0.09). After
      adjustment for age, neuroretinal rim area and the other IOP measurements, age
      (P<0.001) and neuroretinal rim area (P=0.05) remained as significant predictive
      factors in the selected Cox model. In the normal-pressure glaucoma group (n=174
      eyes), progression was significantly positive associated with the minimal IOP
      value (P<0.001), the mean of the IOP values (P=0.024), and, less significantly
      (P=0.037) and negatively, with the pressure profile amplitudes. In the high
      pressure glaucoma group (n=681 eyes), rate of glaucoma progression was not
      associated with the IOP amplitude (P=0.734) or the other IOP parameters.
      CONCLUSIONS: Taking into account the highly significant associations between the
      IOP amplitude and the mean, minimal and maximal IOP values suggests that it is
      the IOP itself, and less the pressure amplitude, which has the main influence on
      the rate of the glaucoma progression.

PMID- 16601738
TI  - Two useful techniques of pars plana vitrectomy using endoscope.

PMID- 16601739
TI  - Aberrant congenital macular vessel crossing the fovea: evaluation with optical
      coherence tomography.

PMID- 16601740
TI  - Structural and functional outcome of scleral patch graft.
AB  - PURPOSE: To evaluate the visual and structural outcomes of scleral patch grafting
      in cases of scleral defect. METHODS: The study was a retrospective interventional
      case series. Medical records of all patients who underwent scleral patch grafting
      at a tertiary care centre between 1997 and 2003 for scleral defects were
      reviewed. After removal of all the devitalized tissue, alcohol-preserved full
      thickness sclera was tailored to fit the defect and sutured in place. The graft
      was covered with a conjunctival flap or amniotic membrane. Structural integrity
      and visual outcome were assessed as the main outcome measures. RESULTS: A total
      of 13 eyes of 13 patients required scleral patch grafting for scleral defects of
      varying aetiologies, the most common being necrotizing scleritis following
      pterygium surgery (40%). The patients were followed up for 6-60 months, an
      average period of 24.3 months. Tectonic success was achieved in 10 eyes (76.9%).
      Three complications were noted: endophthalmitis, graft necrosis, and graft
      dehiscence with uveal prolapse. However, no regrafts were needed.
      Epithelialization and vascularization were seen in the remaining eyes after an
      average duration of 3-4 weeks. Visual acuity remained stable in the majority
      (9/13, 60%), improved in one and deteriorated in three eyes. CONCLUSIONS: Scleral
      grafting with overlying conjunctival or amniotic membrane graft is an effective
      and simple measure for preserving globe integrity both structurally and
      functionally.

PMID- 16601741
TI  - Expression of chemokines and gelatinase B in sympathetic ophthalmia.
AB  - PURPOSE: To examine the expression of gelatinase B (matrix metalloproteinase-9)
      and the chemokines monocyte chemotactic protein-1 (CCL2/MCP-1) and stromal cell
      derived factor-1 (CXCL12/SDF-1) in sympathetic ophthalmia (SO). METHODS: Five
      enucleated exciting eyes with a clinical diagnosis and typical histopathological
      findings of SO were studied by immunohistochemical techniques using a panel of
      monoclonal antibodies directed against gelatinase B, MCP-1, and SDF-1. In
      addition, a panel of monoclonal and polyclonal antibodies was used to
      characterize the composition of the inflammatory infiltrate. RESULTS: In all
      cases, the extensive uveal inflammatory infiltrate was organized as a diffuse
      infiltrate and as large granulomas consisting of epithelioid cells and
      multinucleated giant cells. CD20(+) B lymphocytes predominated in the diffuse
      infiltrate and CD3(+) T lymphocytes were few. The monocyte/macrophage marker CD68
      was expressed in scattered inflammatory mononuclear cells and within granulomas
      and Dalen-Fuchs nodules. Most of the inflammatory cells were HLA-DR(+).
      Immunoreactivity for gelatinase B, MCP-1, and SDF-1 was observed in cells within
      granulomas and in scattered epithelioid cells. Immunoreactivity for MCP-1 was
      noted in retinal pigment epithelial cells. Endothelial cells of choriocapillaries
      showed weak immunoreactivity for SDF-1. CONCLUSIONS: Gelatinase B, MCP-1, and SDF
      1 might have a pathogenic role in the recruitment of leucocytes into the eye in
      SO.

PMID- 16601742
TI  - Combined removal of silicone oil plus internal search (ROSO-plus) following
      retinal detachment surgery.
AB  - PURPOSE: To report the rate of retinal redetachment and intervention with
      combined removal of silicone oil plus internal search (ROSO-plus) and to report
      the pathology identified. METHODS: Preoperative and peroperative findings were
      related to postoperative failure of the surgery defined as retinal redetachment
      postoperatively or silicone oil in situ at the final follow-up. RESULTS: Sixty
      three patients were included in the study. Mean follow-up was 13 months.
      Retinopexy and further tamponade were used in 22 patients. Overall 'ROSO-plus'
      failed in 13 (21%) patients. Patients with subretinal fluid (SRF) in the inferior
      quadrants of the fundus during 'ROSO-plus' were particularly at risk of failure
      at 86% (six of seven patients) vs 12.5% (7/56) for the remainder (P=0.0002,
      relative risk=6.9, 95% confidence interval 3.2-14.6). The overall success rate at
      final follow-up (after any further surgery) for a flat retina without oil in situ
      was 83%. CONCLUSION: The 'ROSO-plus' procedure allowed identification of problems
      expected to result in anatomical failure. Treatment did not prevent a high rate
      of postoperative retinal detachment. Refinement of the treatment algorithm is
      required with perhaps more use of silicone oil reinsertion in high-risk eyes.

PMID- 16601743
TI  - Intractable glaucoma following posterior sub-tenon's triamcinolone acetonide for
      central retinal vein occlusion in a young adult.

PMID- 16601744
TI  - Vitreoretinal surgery after childhood ocular trauma.
AB  - AIM: In adults modern vitreoretinal surgery allows many traumatised eyes to be
      salvaged. However, one third of serious eye injuries occur in the paediatric age
      group and trauma is a leading cause of monocular blindness in childhood. This
      study aims to report the indications, complications and outcomes for
      vitreoretinal surgical intervention after childhood ocular trauma. METHODS:
      Retrospective case note review of 61 children (age 16 years or less) undergoing
      vitreoretinal surgical procedures following ocular trauma at a tertiary referral
      centre. RESULTS: Twenty-eight children (45.9%) had open globe injuries (OGI) and
      33 closed globe injuries (CGI, 54.1%). The mean age of children with OGI was 9.5
      years and with CGI 12.3 years (P=0.0068). Forty-seven children had traumatic
      retinal detachments (77.1%), which in 17 cases were treated with conventional
      scleral buckling surgery and in 30 by vitrectomy. Retinal re-attachment was
      achieved after one procedure in 70.6% with scleral buckling and 46.7% with
      vitrectomy. Fourteen children (22.9%) had attached retinas but required
      vitrectomy for other reasons. After a mean follow-up of 19.6 months, the median
      visual acuity (VA) of the children improved from counting fingers at presentation
      to 6/36 at final review (P=0.0031). Traumatic retinal detachment requiring
      vitrectomy was associated with poor visual outcome (P=0.0003). CONCLUSION:
      Vitreoretinal intervention resulted in an improvement in vision in 32 children
      (57.1%) and stabilised 11 at their presenting acuity (19.6%). Two thirds of the
      children attained a final VA of 6/60 or better. Proliferative vitreoretinopathy
      was the cause of redetachment in 68.2% of cases and was significantly associated
      with a poor outcome (P<0.0001).

PMID- 16601745
TI  - The use of Campath in severe peripheral ulcerative keratitis associated with
      Wegener's granulomatosis.

PMID- 16601746
TI  - Evaluation of efficacy and safety of daunorubicin in glaucoma filtering surgery.
AB  - PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect and ocular
      side effects of daunorubicin (DNR) in drug-modulated trabeculectomy. METHODS: A
      prospective pilot study was conducted in which 21 Asian patients of Indian origin
      with high risk factors for failure of trabeculectomy were recruited. An approval
      from research ethics committee and an informed consent from every patient
      included in the study were obtained. DNR, an antimetabolite with known
      antifibroblastic action was used intraoperatively. A limbus-based conjunctival
      flap followed by conventional trabeculectomy was performed in all eyes. During
      trabeculectomy, a cellulose sponge soaked in 0.2 mg/ml DNR was applied for 3 min
      at the proposed site of trabeculectomy before preparation of the partial
      thickness scleral flap. A regular follow-up was carried out for 1 year where
      parameters including visual acuity, IOP by applanation tonometry, and slit lamp
      examination were performed on each visit. An IOP of 21 mmHg or less was taken as
      criteria for success. RESULTS: Following DNR trabeculectomy, the IOP was lowered
      from baseline preoperative value of 36.19+/-5.9 to 16.05+/-2.52 mmHg at the end
      of 1 year. Success rate of 81% (17 out of 21 patients) was noted. None of the
      patients developed corneal epithelial toxicity, hypotony maculopathy, or
      choroidal detachment. CONCLUSION: The authors feel that intraoperative
      daunorubicin is safe and effective in lowering IOP in high-risk surgical cases of
      glaucoma. However, a much larger cohort study over a considerable number of years
      will eventually demonstrate its safety.

PMID- 16601747
TI  - The influence of posterior capsule opacification on scanning laser polarimetry.
AB  - PURPOSE: To evaluate the influence of posterior capsule opacification (PCO) on
      GDx parameters in a population of pseudophakic, non-glaucomatous patients who
      underwent Nd:YAG laser capsulotomy (YLC). METHODS: The posterior capsules were
      photographed with a Topcon digital camera and each image was then entered into
      the EPCO 2000 software and evaluated independently by three examiners. The EPCO
      2000 software was used to calculate the fibrosis index (FI) and the pearl index
      (PI) for the central 1.5, 2.5, and 3.5 mm of the posterior capsule. Scanning
      laser polarimetry was performed with GDx before and after YLC. We compared the
      GDx readings obtained before and after the YLC using paired Student's t-test. The
      parameters that varied significantly after YLC were subsequently used for
      regression analysis. Stepwise multiple linear regression was used to analyse the
      impact of the change in the amount of FI and PI on change in GDx parameters after
      YLC. RESULTS: In total, 158 patients were enrolled (74 men, 84 women). The mean
      age was 69.46+/-8.83 years (range 46-83 years). The interobserver agreement among
      the three experts was found to be good (repeatability coefficient R=1.51, 1.49,
      1.49 for observer A vs B, A vs C, and B vs C respectively). One-sample Student's
      t-test show no difference between all GDx parameters before and after YLC except
      for Symmetry, Superior/Nasal ratio, Inferior Ratio, and Temporal-Superior-Nasal
      Inferior-Temporal (TSNIT). Stepwise multiple regression showed that the two
      variables of greatest significance for changes in Symmetry were the FI in the
      central 1.5 and the PI in the central 3.5 mm (P=0.02). Superior/nasal ratio was
      shown to be most strongly correlated to the FI in the central 1.5 mm and PI in
      the central 3.5 mm (P<0.001), whereas the variable of greatest significance to
      Inferior Ratio was PI in the central 3.5 mm (P=0.03). Finally, TSNIT was most
      strongly correlated to FI in the central 1.5 mm and FI in the central 2.5 mm
      (P<0.001). CONCLUSION: Presence of capsular fibrosis seems to be more clinically
      relevant in the central zone, whereas pearls tend to be clinically significant in
      the central 3.5 mm area. Hence, it might be worthwhile assessing the amount of
      PCO in pseudophakic patients when performing scanning laser polarimetry.
      Investigators should ensure that the type of PCO and the size of the area
      analysed are documented in the notes in order to interpret GDx findings
      appropriately.

PMID- 16601748
TI  - Retinal function in infants with optic nerve hypoplasia: electroretinograms to
      large patterns and photopic flash.
AB  - AIMS: Optic nerve hypoplasia (ONH), which is defined as a congenital deficiency
      of retinal ganglion cells, may also involve more distal layers of the retina. We
      investigated electrophysiological function of the retina in ONH using
      electroretinograms (ERGs). METHODS: ERGs were recorded from 48 subjects (3.5-35
      months) with unilateral or bilateral ONH. Pattern reversal (4 degrees checks) was
      presented under chloral hydrate sedation, using an optical system to correct a
      cycloplegic refraction. A photopic flash stimulus was also used. Fundus
      photographs were used to measure the disk diameter/disk macula ratio (DD/DM), and
      to document other clinical signs. Eyes were classified as moderate (0.15-0.3) or
      severe (<0.15) ONH, and those with DD/DM greater than 0.3 were used as reference
      eyes. RESULTS: Pattern ERG recording was completed in 89 eyes and was detectable
      in 80% of eyes with ONH (61/76 tested) and in all 13 reference eyes. Photopic
      flash ERGs were of good quality in all eyes. The severity of ONH correlates with
      the amplitude of the photopic flash b-waves and with the amplitude of the N95
      component of the pattern ERG (P<0.01). However, the ERGs to large patterns were
      well preserved (>3.5 microV) in 10 of 35 eyes with severe ONH. Tortuous retinal
      vessels in eyes with either moderate or severe ONH were associated with smaller
      amplitude photopic b-waves and markedly diminished or undetectable pattern ERGs.
      CONCLUSIONS: This study supports the hypothesis that retinal dysfunction distal
      to the ganglion cells is common in ONH, but is not predictable on the basis of
      ONH severity alone. Additionally, tortuous retinal vessels in ONH may be a sign
      associated with retinal dysfunction.

PMID- 16601749
TI  - Differential roles of p63 isoforms in epidermal development: selective genetic
      complementation in p63 null mice.
AB  - Epidermal development requires the transcription factor p63, as p63-/- mice are
      born dead, without skin. The gene expresses two proteins, one with an amino
      terminal transactivation domain (TAp63) and one without (deltaNp63), although
      their relative contribution to epidermal development is unknown. To address this
      issue, we reintroduced TAp63alpha and/or deltaNp63alpha under the K5 promoter
      into p63-/- mice by in vivo genetic complementation. Whereas p63-/- and p63-/-;TA
      mice showed extremely rare patches of poorly differentiated keratinocytes, p63-/
      ;deltaN mice showed significant epidermal basal layer formation. Double
      TAp63alpha/deltaNp63alpha complementation showed greater patches of
      differentiated skin; at the ultrastructural level, there was clear reformation of
      a distinct basal membrane and hemidesmosomes. At the molecular level, deltaNp63
      regulated expression of genes characteristic of the basal layer (K14),
      interacting (by Chip, luc assay) with the third p53 consensus site. Conversely,
      TAp63 transcribed the upper layer's genes (Ets-1, K1, transglutaminases,
      involucrin). Therefore, the two p63 isoforms appear to play distinct cooperative
      roles in epidermal formation.

PMID- 16601750
TI  - The complexity of p53 stabilization and activation.
AB  - A number of proteins are activated by stress stimuli but none so spectacularly or
      with the degree of complexity as the tumour suppressor p53 (human p53 gene or
      protein). Once stabilized, p53 is responsible for the transcriptional activation
      of a series of proteins involved in cell cycle control, apoptosis and senescence.
      This protein is present at low levels in resting cells but after exposure to DNA
      damaging agents and other stress stimuli it is stabilized and activated by a
      series of post-translational modifications that free it from MDM2 (mouse double
      minute 2 but used interchangeably to denote human also), a ubiquination ligase
      that ubiquitinates it prior to proteasome degradation. The stability of p53 is
      also influenced by a series of other interacting proteins. In this review, we
      discuss the post-translational modifications to p53 in response to different
      stresses and the consequences of these changes.

PMID- 16601751
TI  - A cytochrome c-free fly apoptosome.

PMID- 16601752
TI  - Higher potency of the synthetic retinoid MX3350-1 compared to the natural all
      trans-retinoic acid in modulation of cell cycle and induction of apoptosis in
      head and neck squamous carcinoma cells.

PMID- 16601753
TI  - p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation
      and response to stress.
AB  - p63, p73 and p53 compose a family of transcription factors involved in cell
      response to stress and development. p53 is the most frequently mutated gene in
      cancer (50%) and loss of p53 activity is considered to be ubiquitous to all
      cancers. Recent publications may have a profound impact on our understanding of
      p53 tumour suppressor activity. p63, p73 and p53 genes have a dual gene structure
      conserved in drosophila, zebrafish and man. They encode for multiple p63, p73 or
      p53 proteins containing different protein domains (isoforms) due to multiple
      splicing, alternative promoter and alternative initiation of translation. In this
      review, we describe the different isoforms of p63, p73, p53 and their roles in
      development and cancer. The changes in the interactions between p53, p63 and p73
      isoforms are likely to be fundamental to our understanding in the transition
      between normal cell cycling and the onset of tumour formation.

PMID- 16601754
TI  - Contribution of guanine exchange factor H1 in phorbol ester-induced apoptosis.
AB  - Phorbol-12-myristate-13-acetate (PMA) treatment induces erythroblastoma D2 cells
      kept in suspension to undergo RhoA-dependent contraction and to become
      proapoptotic, while attached cells are induced to differentiate accompanied by
      the reduction of RhoA activity. In this study, we found that guanine exchange
      factor H1 (GEF-H1) is highly expressed in D2 cells. Depletion of GEF-H1
      expression in D2 cells decreased RhoA activity and prevented PMA-induced
      contraction and apoptosis. Upon PMA stimulation, GEF-H1 became associated with
      microtubules in cells that were induced to differentiate. As a contrast, in the
      proapoptotic population of cells GEF-H1 stayed in the cytoplasm without showing
      PMA-responsive microtubule translocation. Given that GEF-H1 is inactivated when
      associated with microtubules and its release into cytosol due to depolymerization
      of microtubules activates RhoA, our results demonstrated that nonmicrotubule
      associated GEF-H1 in D2 cells contributes to the sustained activation of
      RhoA/ROCK signaling in suspension cells, making cells susceptible to PMA-induced
      apoptosis.

PMID- 16601755
TI  - Molecular mechanism of genotoxicity of the environmental pollutant 3
      nitrobenzanthrone.
AB  - 3-Nitrobenzanthrone (3-NBA) is a suspected human carcinogen identified in diesel
      exhaust and air pollution. This article reviews the results of our laboratories
      showing which of the phase I and II enzymes are responsible for 3-NBA
      genotoxicity, participating in activation of 3-NBA and its human metabolite, 3
      aminobenzanthrone (3-ABA), to species generating DNA adducts. Among the phase I
      enzymes, the most of the activation of 3-NBA in vitro is attributable to
      cytosolic NAD(P)H:quinone oxidoreductase (NQO1), while N,O-acetyltransferase
      (NAT), NAT2, followed by NAT1, sulfotransferase (SULT), SULT1A1 and, to a lesser
      extent, SULT1A2 are the major phase II enzymes activating 3- NBA. To evaluate the
      importance of hepatic cytosolic enzymes in relation to microsomal
      NADPH:cytochrome P450 (CYP) oxidoreductase (POR) in the activation of 3-NBA in
      vivo, we treated hepatic POR-null and wild-type C57BL/6 mice with 3-NBA or 3-ABA.
      The results indicate that 3-NBA is predominantly activated by cytosolic
      nitroreductases such as NQO1 rather than microsomal POR. In the case of 3-ABA,
      CYP1A1/2 enzymes are essential for the oxidative activation of 3-ABA in liver.
      However, cells in the extrahepatic organs have the metabolic capacity to activate
      3-ABA to form DNA adducts, independently from CYP-mediated oxidation in the
      liver. Peroxidases such as prostaglandin H synthase, lactoperoxidase,
      myeloperoxidase, abundant in several extrahepatic tissues, generate DNA adducts,
      which are formed in vivo by 3-ABA or 3-NBA. The results suggest that both CYPs
      and peroxidases may play an important role in metabolism of 3-ABA to reactive
      species forming DNA adducts, participating in genotoxicity of this compound and
      its parental counterpart, 3-NBA.

PMID- 16601756
TI  - Hair analysis for drugs of abuse. Plausibility of interpretation.
AB  - Over more than 20 years hair analysis for drugs has been gaining increasing
      attention and recognition in various toxicological fields as preemployment and
      employment screening, forensic sciences, doping control of banned substances,
      clinical diagnostics in health problems. Hair analysis for drugs can expand the
      toxicological examination of conventional materials and thus contribute with
      additional important information to the complex evaluation of a certain case.
      Hair is a unique material for the retrospective investigation of chronic drug
      consumption, intentional or unintentional chronic poisoning in criminal cases,
      gestational drug exposure or environmental exposure to pollutants and adulterants
      and with specific ultrasensitive procedures allow to demonstrate even a previous
      single dose administration in a very low amount. Assuming the ideal hair steady
      and uniform growth, segmental hair analysis can provide the information about the
      time course of the substance use or exposure. However, the physiological
      background of hair growth, mechanisms of drug incorporation are not simple, not
      yet understood in full details and need not be evaluated exactly in all cases.
      The hair sampling, storage, sample preparation, analytical performance themselves
      are also very important for final results. Different laboratory attitudes can
      produce different results. The full information on circumstances of the case
      examined must be taken into account during interpretation. The pitfalls in hair
      analysis should be known and avoided to assure the responsible and correct
      interpretation of laboratory results adequate to an individual case.

PMID- 16601757
TI  - Developmental toxicology - an integral part of safety evaluation of new drugs.
AB  - The thalidomide tragedy stimulated an intense research in the etiology,
      prevention and treatment of congenital malformations. The Government requires
      that drugs and food additives be evaluated pre-clinically for toxicity, including
      developmental toxicity, before being marketed. The number of compounds which must
      be tested has increased dramatically with the continuous development of
      therapeutic, cosmetic and food additive chemicals. Such tests include: in vitro
      studies which can serve as efficient pre-screens to rank chemicals for further
      batteries of in vivo tests on pregnant animals. However, the safety of any drug
      would be determined only by a post-marketing epidemiological survey. Taking into
      account the altered susceptibility to different drugs in a pregnant individual,
      it could be said that administration of any drug during the first trimester is an
      experiment in human teratology.

PMID- 16601758
TI  - Microtubule disruptors and their interaction with biotransformation enzymes.
AB  - Microtubule disruptors, widely known as antimitotics, have broad applications in
      human medicine, especially as anti-neoplastic agents. They are subject to
      biotransformation within human body frequently involving cytochromes P450.
      Therefore antimitotics are potential culprits of drug-drug interactions on the
      level of activity as well as expression of cytochromes P450. This review
      discusses the effects of four well-known natural antimitotics: colchicine, taxol
      (paclitaxel), vincristine, and vinblastine, and a synthetic microtubule disruptor
      nocodazole on transcriptional activity of glucocorticoid and aryl hydrocarbon
      receptors. It appears that microtubules disarray restricts the signaling by these
      two nuclear receptors regardless of cell cycle phase. Consequently, intact
      microtubules play an important role in the regulation of expression of
      cytochromes P450, which are under direct or indirect control of the two nuclear
      receptors.

PMID- 16601759
TI  - Experimental toxicology in silico.
AB  - A review on applicability of in silico methods for toxicity testing by
      calculation for regulatory purposes, their survey and background of QSAR
      (Quantitative Structure-Activity Relationships) analysis are presented.

PMID- 16601760
TI  - What are artificial neural networks and what they can do?
AB  - The artificial neural networks (ANN) are very often applied in many areas of
      toxicology for the solving of complex problems, such as the prediction of
      chemical compound properties and quantitative structure-activity relationship.
      The aim of this contribution is to give the basic knowledge about conception of
      ANN, theirs division and finally, the typical application of ANN will be
      discussed. Due to the diversity of architectures and adaptation algorithms, the
      ANNs are used in the broad spectrum of applications from the environmental
      processes modeling, through the optimization to quantitative structure-activity
      relationship (QSAR) methods. In addition, especially ANNs with Kohonen learning
      are very effective classification tool. The ANNs are mostly applied in cases,
      where the commonly used methods does not work.

PMID- 16601761
TI  - Matrix metalloproteinases and their function in myocardium.
AB  - A significant number of myocardial diseases are accompanied by increased
      synthesis and degradation of the extracellular matrix (ECM) as well as by changed
      maturation and incorporation of ECM components. Important groups of enzymes
      responsible for both normal and pathological processes in ECM remodeling are
      matrix metaloproteinases (MMPs). These enzymes share a relatively conserved
      structure with a number of identifiable modules linked to their specific
      functions. The most important function of MMPs is the ability to cleave various
      ECM components; including such rigid molecules as fibrillar collagen molecules.
      The amount and activity of MMPs in cardiac tissue are regulated by a range of
      activating and inhibiting processes. Although MMPs play multifarious roles in
      many myocardial diseases, here we have focused on their function in ischemic
      cardiac tissue, dilated cardiomyopathy and hypertrophied cardiac tissue. The
      inhibition of MMPs by means of synthetic inhibitors seems to be a promising
      strategy in cardiac disease treatment. Their effects on diseased cardiac tissue
      have been successfully tested in several experimental studies.

PMID- 16601762
TI  - The metabolic syndrome: relationship between insulin sensitivity and the role of
      peroxisome proliferator-activated receptors (PPARs) in saccharide and lipid
      metabolism.
AB  - Peroxisome proliferator-activated receptors (PPARs) are subgroups of nuclear
      hormonal receptors of transcripting factors mostly found in adipose tissue. They
      are described as important regulators of lipid and saccharide metabolism
      including insulin sensitivity; therefore they are taken as marker of metabolic
      syndrome. Their synthetic ligands could be used as drugs for insulin resistance
      and type 2 diabetes mellitus.

PMID- 16601763
TI  - Heat shock proteins in autoimmune diseases.
AB  - Heat shock proteins (hsp's) are among the most conserved proteins in evolution.
      They have been identified as important pathogen-related antigens as well as
      autoantigens suitable for construction of novel vaccines. The high evolutionary
      homology of hsp's has raised the question about the safety of such vaccines.
      Experimental and clinical observations have confirmed that hsp proteins are
      involved in the regulation of some autoimmune disease such as autoimmune
      arthritis, type 1 diabetes mellitus, atherosclerosis, multiple sclerosis, and
      other autoimmune reactions. It has been shown in experimental animals that some
      hsp proteins (especially hsp60, hsp70, and hsp10) can either induce or prevent
      autoimmune reactions depending on the circumstances. This article discusses the
      involvement of hsp proteins in the etiology of autoimmune diseases and it
      presents promising experimental data on the effects of immunization with hsp
      proteins in the prevention and therapy of autoimmune diseases.

PMID- 16601764
TI  - Changes in mRNA levels of intracellular fatty acid metabolism regulators in human
      hepatoma HepG2 cells following their treatment with non-esterified fatty acids
      and dehydroepiandrosterone.
AB  - The effects of non-esterified fatty acids (NEFA) and hormone
      dehydroepiandrosterone (DHEA) on the levels of mRNAs of protein kinase C (PKC) 
      delta and -epsilon isoforms and those of liver fatty acid binding protein (L
      FABP) were investigated in the human hepatoma HepG2 cell line. The cells were
      kept in low-serum, low-albumin medium during experiments. Low FA levels (100
      microM) and time intervals of 4 h and 20 h were used. In these conditions, the
      saturated (palmitic, stearic) and monounsaturated (oleic) acids rather
      selectively stimulated PKC-epsilon mRNA levels. Unexpectedly, we found that these
      acids also suppressed liver fatty-acid binding protein (L-FABP) mRNA levels. DHEA
      in pharmacological doses (100 microM) produced a significant increase in PKC
      delta and -epsilon mRNA levels. Although molecular mechanisms underlying the
      identified changes have not been investigated in this paper, our findings
      emphasize that NEFA-induced modulation of mRNA levels of key signalling
      components represent an additional mechanism for how the ambient NEFA can
      influence metabolic homeostasis in cells.

PMID- 16601765
TI  - Preparation and purification of recombinant outer surface protein A (rOspA) of
      Borrelia burgdorferi sensu stricto and Borrelia afzelii.
AB  - The recombinant Outer surface protein A (rOspA) from Borrelia burgdorferi is a
      possible immunogen for protection of infected humans and animals against
      development of Lyme borreliosis (Lyme disease), a chronic tick-borne disease
      characterised by diverse dermatologic, neurologic, rheumatic, and cardiac
      manifestations. For several years, research and development have been directed
      towards a vaccine for the prevention of this debilitating disease. Numerous
      animal studies demonstrate that pre-existing antibodies against the outer surface
      proteins of B. burgdorferi can prevent infection and disease caused by this
      organism. In this communication, using recombinant DNA technology, genes from B.
      burgdorferi sensu stricto and B. afzelii were inserted into E. coli-expression
      vectors and the rOspA were produced. Our aim was to obtain rOspA protein in a
      purity and quantity desirable for immunization of experimental animals. rOspA is
      currently the most developed, molecularly-defined vaccine candidate for the
      prevention of Lyme borreliosis.

PMID- 16601766
TI  - Isolation and purification of recombinant outer surface protein C (rOspC) of
      Borrelia burgdorferi sensu lato.
AB  - The aim of this work was isolation and purification of the major immunodominant
      protein, Outer surface protein C (OspC) of three members of the species group
      Borrelia burgdorferi, the causative agent of Lyme disease. Our aim was to obtain
      this protein in a quantity and purity sufficient for immunization of experimental
      animals. For optimalization of protein purification's yield we used immobilized
      metal ion affinity chromatography (IMAC) under different conditions. The greatest
      efficiency was achieved by using of HiTrap Chelating Column under native
      conditions.

PMID- 16601767
TI  - Applications of new laboratory marker assays in neurological diagnoses - a pilot
      study.
AB  - 225 consecutive patients with different neurological diseases and 101 individuals
      as the control were examined between 2002-2004. Cystatin C, arginase-I, tau
      protein and beta-amyloid were measured. Individuals with CNS inflammation had
      significantly lower Cystatin-C index (CSF/serum) values. There was no diagnostic
      significance of the Arginase-I assay in CSF was verified. The CSF tau
      protein/beta-amyloid index was shown to be a sufficient efficacy for
      neurodegenerative disease diagnosis.

PMID- 16601768
TI  - Pharmacotherapeutical approaches to decreasing hematocrit and increasing
      claudication distance in diabetic patients with peripheral vascular disease.
AB  - The paper deals with pharmacotherapeutical approaches to decreasing hematocrit in
      order to improve macro and microcirculation in arteries of lower limbs of type 2
      diabetes patients. The study included 37 patients with diabetic angiopathy, all
      of whom had inoperable changes to arteries. In order to decrease hematocrit and
      cause haemodilution, we used 10 % solution of hydroxyethyl starch. Indications
      for inclusion in the study were carried out in close cooperation with a vascular
      surgeon. We applied hydroxyethyl starch according to a predetermined scheme.
      Using normovolemic and hypervolemic haemodilution, we decreased hematocrit to
      0.41-0.42. Patients underwent a treadmill examination at the beginning of the
      study and then repeatedly during the course of study, when we measured the
      claudication distance to quantify, the effects of decreased hematocrit. The
      results show that the effect is most pronounced after 6 weeks, when hematocrit
      fell from a baseline of 0.435 to 0.421 (p < 0.01) and claudication distance
      increased to 51% (also significant). On average the claudication distance rose
      from 55.7 m to 84.6 m (p < 0.01). In the following weeks (after the sixth week of
      the study), the studied parameters changed only insignificantly (p > 0.05).

PMID- 16601769
TI  - Evaluation of plasma cell propidium-iodide and annexin-V indices: their relation
      to prognosis in multiple myeloma.
AB  - In a group of 117 patients with multiple myeloma (MM) examined at the time of
      diagnosis, i.e. excluding previous chemotherapy, we analysed the levels of
      propidium-iodide (proliferative) - PC-PI/CD(138) and annexin-V (apoptotic) - PC
      AI/CD(138) indices of myeloma plasmocytes using the method of flow-cytometry to
      determine their relationship to prognosis. It was revealed that patients with
      high values of PC-PI/CD(138) had substantially worse overall survival than those
      with low values. Patients with a level of propidium-iodide index > or = 2,8 %
      exprimed a median survival of 13 months only in comparison with 42 months in
      patients with levels < 2,8 % (p = 0,0005). In the PC-AI/CD(138) index a reverse
      trend was registered. Patients with PC-AI/CD(138) > or = 4,0 % had long overall
      survival (median was not assessable at the time of evaluation), whereas patients
      with low apoptosis values < 4,0 % had median overall survival 16 months only (p =
      0,01). Based on the sequentional graphic analysis of the curves of overall
      survival was found that the optimal discrimination level sequestering patients
      with good and poor prognosis was, in the case of PC-PI/CD(138) value 2,8 %,
      whereas in the case of PC-AI/CD(138) value 4,0 %. Among patients with good
      prognosis, there were no statistically significant differences in overall
      survival according to different levels of proliferative and apoptotic index. We
      conclude that evaluation of the propidium-iodide and annexin-V index using flow
      cytometry is a quick, useful, and easily accessible method for the evaluation of
      plasma cell kinetics and thus prognosis of the disease, multiple myeloma.

PMID- 16601770
TI  - T-cell gamma/delta hepatosplenic lymphoma - prolonged remission induced by
      aggressive first line treatment.
AB  - T-cell gamma/delta hepatosplenic lymphoma is a primary extranodal lymphoma,
      distinct from other T/LGL lymphomas. The clinical course is aggressive, and
      despite use of the multiagent chemotherapy and young age of the patients, the
      median survival is less than 1 year. Curability of this disease is still
      uncertain. We reported a case of the successful intensive treatment with
      splenectomy, chemotherapy a first line autologous stem cell transplant. High
      intensity cytarabine- platinum containing regimen (EDHAP) may overcome primary
      resistance to conventional alkylating agents.

PMID- 16601771
TI  - Arthroscopic treatment of ruptures of the rotator cuff.
AB  - 566 patients with shoulder disease were treated at the Clinic of Orthopaedics at
      the University Hospital Olomouc. Of these, 181 were operated for ruptures of the
      rotator cuff (RC). They were categorised according to the Gschwend
      classification, age and gender(1). Laterality of the operated limb was also
      evaluated. Patients with ruptures larger than 4 cm were treated by open
      operation. 84 shoulders with ruptures classified as Gschwend I, II and IIIa -52
      males and 32 females-were treated arthroscopically. The age of the operated
      patients ranged from 40-60 years. In both genders, the right shoulder was more
      often affected. Two operating techniques were used: 1) Transosseal refixation of
      the RC muscle tendons, using RC MITEK anchor implants, 2) "End to end" sutures,
      without implants(2-4). Operating time was reduced to 30-40 min. The operating
      results were evaluated according to the UCLA criteria- University of California
      Shoulder Rating Score(2). 45 patients achieved excellent results (53 %), 35
      patients had good results (42 %), and 4 patients (5 %) obtained satisfactory
      results. None of the patients obtained poor results- a score of less than 20 was
      poor. Patients felt comfortable following the operation and none had any post
      operational complications. The author is convinced, along with others, that
      arthroscopic suturing of RC ruptures classified I-IIIa allows for rupture
      treatment that in the past had to be treated by open technique(2-5). The deltoid
      muscle is not affected by arthroscopy. There is normalisation of the patient's
      movement, pain, force, and rotational stability is comparable to the healthy
      limb. Treatment time is reduced to a minimum and the patient may soon return to
      normal daily life.

PMID- 16601772
TI  - Burch-Schneider cage fracture: a case report.
AB  - In this report, we present the case of a 64-year-old woman who sustained a Burch
      Schneider cage fracture. Prior to this event, she underwent repeated acetabular
      reconstructions, but in the end prosthesis removal was performed as a salvage
      procedure. We believe that the primary cause of the fracture was metal fatigue
      facilitated by intraoperative re-contouring of the flange, as well as reuse of
      the cage. Based on this case we caution against repetitive or excessive flange
      bending during implantation of Burch-Schneider cages and do not recommend their
      reuse.

PMID- 16601773
TI  - Universal primers for detection of common bacterial pathogens causing prosthetic
      joint infection.
AB  - The diagnosis of low grade prosthetic joint infection is difficult and time
      consuming. Nested-PCR for universal bacterial DNA segments detection of
      "orthopaedic" bacteria was tested in a laboratory setting. This method is based
      on amplification of the 16S bacterial ribosomal RNA coding sequences. 11 species
      of the most frequent bacterial pathogens (Staphylococcus aureus, Staphylococcus
      epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus
      faecium, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Proteus
      mirabilis, Pseudomonas aeruginosa, Serratia marcescens) involved in prosthetic
      joint infections were studied. All could be detected rapidly and sensitively by
      this method.

PMID- 16601774
TI  - Bronchial asthma and Chlamydia pneumoniae antibodies in children aged 4-8 years
      in Olomouc district.
AB  - BACKGROUND: Although several studies have demonstrated an association between
      infection with Chlamydia pneumoniae and asthma, these were mainly limited to
      exacerbation of symptoms in adults with known asthma OBJECTIVE: We investigated
      the role of C. pneumoniae infection in 149 atopic children with chronic cough and
      asthma, comparing them with 241 control non-atopic subjects presenting at Olomouc
      hospital between 1999 and 2003 with non-specific symptoms (temperature above
      normal (subfebrile), abdominal pain, arthralgia, and other symptoms. METHODS: The
      levels of C. pneumoniae-specific antibodies were measured using Chlamydien-rELISA
      kits (Medac, Hamburg, Germany). RESULTS: In a group of 83 atopic children with
      chronic cough, IgM and IgG antibodies to C. pneumoniae were demonstrated in 20
      children (24 %). Among children with bronchial asthma, positive antibody was
      present in 29 children (44 %; /p = 0,052/); of this number, 24 (36 %; /p = 0,06/)
      had IgM and IgG antibodies while 5 children (8 %) had IgA and IgG antibodies
      against C. pneumoniae. A group of non-atopic children with non-specific symptoms
      included 38 children (16 %) with antibody positivity; 27 children (11 %) with IgM
      and IgG antibodies and 11 children (5 %) with IgA and IgG antibodies against C.
      pneumoniae. CONCLUSIONS: Asthma in children was associated with elevated levels
      of IgM and IgG antibodies to C. pneumoniae.

PMID- 16601775
TI  - Risk factors for cardiovascular diseases in physicians.
AB  - The aim of the study was to determine the prevalence of risk factors for
      cardiovascular diseases among physicians at a teaching hospital. In total, 203
      men and 167 women were included in the study. The participants filled in a
      questionnaire; their height, weight, blood pressure, serum cholesterol and
      glucose levels were added. 19.2 % males and 13.8 % females were smokers,
      hypertension was diagnosed in 10 % of males and in 6.6 % of females, 52.2 % males
      and 17.4 % females were overweight, 37 % males and 43.1 % females had
      hypercholesterolemia. The above findings suggest that Czech physicians have more
      favourable values of all the studied cardiovascular diseases risk factors than
      the general Czech population. However, Czech physicians smoke more than those in
      other countries and their level of cardiovascular diseases risk factors is
      unsatisfactory and calls for further intensive prevention. Preliminary outcomes
      of the study repeated after two years show no positive trends as well as
      physicians' low willingness to actively participate in lowering cardiovascular
      diseases risk factors.

PMID- 16601776
TI  - Testing of the Biocan B inj. ad us. vet. vaccine and development of the new
      recombinant vaccine against canine borreliosis.
AB  - Verification of the efficacy of Biocan B inj. ad us. vet. (Bioveta, a.s.) was
      done by challenge testing. Ticks collected in the nature were used as natural
      vectors of the infection. Six beagles and two control ones were used in the test.
      Formation of outer surface protein A specific antibodies (OspA antibodies) and
      borrelia specific immonoglobulins (IgG) was measured by Western blot and EIA in
      the sera samples. The tissue samples were used for detection of borreliae by
      cultivation method and dark field microscopy (DFM). Formation of IgG antibodies
      and OspA antibodies after vaccination was observed. The maximum titer level of
      antibodies was reached between 21. and 49. day after vaccination and then slowly
      decreased. Presence of borreliae was detected only in skin biopsies of non
      vaccinated dogs. The post mortem tissue samples showed presence of borreliae in
      all of the samples of the non-vaccinated dogs. The tissues of the vaccinated dogs
      were not infected with borreliae, except for two samples of dog with low titer
      levels of OspA antibodies. The development of the new vaccine is based on
      preparation of recombinant outer surface proteins (e.g. rOspA and rOspC) of B.
      afzelii, B. burgdorferi and B. garinii origin. Chosen recombinant proteins were
      successfully expressed in E. coli. The obtained purified proteins are currently
      being tested on laboratory BALB/c mice. Formation of specific antibodies against
      some recombinant proteins has been confirmed. These proteins are suitable
      candidates for preparation of a vaccine prototype and they will be subsequently
      used in challenge tests.

PMID- 16601777
TI  - Apoptosis and expression of Bcl-2 in human endometrium in natural and artificial
      cycles.
AB  - Apoptosis plays a significant role in differentiation of many organs and helps to
      maintain homeostasis. The occurrence of apoptosis (using the apoptotic index) and
      expression of regulation protein Bcl-2 in the human endometrium was evaluated
      within the secretory phase of both the natural cycle, and an artificial one. Oral
      hormonal substitution used in this design induced similar, but more marked
      dynamic changes in Bcl-2 expression in the mid-secretory endometrium as were
      observed in the natural cycle, primarily in the surface and glandular epithelium
      of the endometrium. The apoptosis revealed similar a trend, but not significantly
      different.

PMID- 16601778
TI  - Pharmacokinetic conversion study of a new cyclosporine formulation in stable
      adult renal transplant recipients.
AB  - Cyclosporine A (CyA) is a standard component of immunosuppressive regimens. It is
      a critical-dose drug for which a minor change in absorption can have important
      clinical consequences. The aim of the study was to compare the pharmacokinetics
      and safety of the new generic CyA formulation, Equoral capsules, after a switch
      from original formulation, Neoral capsules, in seventy stable adult renal
      transplant recipients. The extent and rate of pharmacokinetic parameters for
      bioequivalence were compared in a non-randomized, steady-state clinical study
      with fixed non-replicate study design. Pharmacokinetic analysis of CyA have shown
      that both the rate and extent of absorption of Equoral does not differ
      significantly from that of Neoral. At identical dosing, the new formulation was
      found to have geometric means of C(max) 717 ng/ml and AUCtau 3108 ng/ml.h, while
      corresponding results of comparator were 725 ng/ml and AUCtau 3039 ng/ml.h,
      respectively. The 90 % confidence intervals of C(max) and AUCtau were within 80-
      125 % interval of the mean values. The results suggest that Equoral capsules can
      be used as an alternative treatment to Neoral capsules in CyA regimen.

PMID- 16601779
TI  - Cytotoxicity of pivoxil esters of antiviral acyclic nucleoside phosphonates:
      adefovir dipivoxil versus adefovir.
AB  - Biological effectiveness of antiviral acyclic nucleoside phosphonate adefo vir, 9
      [2-(phosphonomethoxy)ethy]ade nine (PMEA) and its more lipophilic
      (bis)pivaloyloxymethyl ester prodrug adefovir dipivoxil (bis-POM-PMEA) were
      compared under in vitro conditions in mammalian cell systems. Proliferation of
      murine splenocytes was inhibited in a concentration-dependent manner, the bis-POM
      PMEA being more effective than PMEA. In contrast to PMEA, bis-POM-PMEA inhibited
      production of nitric oxide (NO) in macrophages activated with interferon-gamma
      (IFN-gamma) and lipopolysaccharide (LPS). Viability of both splenocytes and
      macrophages remained uninfluenced by PMEA, whereas pronounced cytocidal effects
      were exhibited by bis-POM-PMEA. The IC(50)s reached the values of 15 microM and
      30 microM in cultures of macrophages and splenocytes, respectively (assayed at
      the interval of 24 hrs). The effects could partly be mimicked by formaldehyde, a
      decomposition product of the pivoxil moiety of bis-POM-PMEA. The other possible
      product, pivalic acid, was ineffective in this respect. The present data are
      consistent with the view that pivoxil prodrug of PMEA, bis-POM-PMEA possesses
      enhanced but also broader spectrum of biological effects than the parent
      compound.

PMID- 16601780
TI  - Modulator of intracellular Ca(2+), thapsigargin, interferes with in vitro
      secretion of cytokines and nitric oxide.
AB  - Interference of thapsigargin (TG), an inhibitor of endoplasmic reticulum Ca(2+)
      ATPase, with immune reactivity of murine macrophages was investigated under
      conditions in vitro. The activation of cells with lipopolysaccharide (LPS),
      interferon-(gamma) (IFN-(gamma)), and with acyclic nucleoside phosphonate N(6)
      isobutyl-9-[2-(phosphonomethoxy)ethyl]- 2,6-diaminopurine (N(6)-isobutyl-PMEDAP)
      resulted in enhanced production of cytokines TNF-alpha, IL-10, chemokines
      RANTES/CCL5 and MIP-1alpha/CCL3, as well as in substantially augmented production
      of nitric oxide (NO) triggered by IFN-(gamma). The effects were in a dual mode of
      action influenced by TG (1 microM). While TG upregulated secretion of TNF-alpha,
      it inhibited secretion of IL-10 and RANTES. The immune-stimulated secretion of
      MIP-1alpha remained virtually unaffected, though TG on its own activated
      expression of MIP-1alpha in macrophages. The high-output NO production induced by
      IFN-(gamma), high concentrations of LPS, or by combination of IFN-(gamma) plus
      LPS or N(6)-isobutyl-PMEDAP was inhibited by TG. On the other hand, production of
      NO which was marginally activated by low concentration of LPS was upregulated by
      TG.

PMID- 16601781
TI  - Phenytoin induced oxidative stress in pre- and postnatal rat development - effect
      of vitamin E on selective biochemical variables.
AB  - A pre- and postnatal study was carried out to investigate the effect of high dose
      (500 mg/kg) of the natural antioxidant vitamin E (VIT E) on biochemical variables
      in the model of chronic intrauterine hypoxia. Chronic hypoxia was induced by
      administration of the anticonvulsant phenytoin (PHT) during pregnancy. Rats were
      orally treated with PHT (150 mg/kg) from day 7 to 18 of gestation and VIT E prior
      to PHT orally on the same days. The activity of the lysosomal enzyme N-acetyl-ss
      D-glucosaminidase (NAGA) and the level of glutathione (GSH) were used as markers
      of tissue damage. In the prenatal study PHT-induced embryofoetal toxicity was
      associated with an increase in NAGA activity and decrease of GSH level in
      maternal serum and heart and with an increase in NAGA activity in the placenta.
      Administration of VIT E did not inhibit the above given changes. PHT increased
      the activity of NAGA and decreased the level of GSH in foetal organs (liver,
      lungs, brain). VIT E did not reverse these changes. In the postnatal study, we
      did not find any significant differences in NAGA activity in the organs of 1-day
      old pups. An increase of liver GSH level was found in PHT and VIT E+PHT groups of
      pups and in the group VIT E+PHT in the lungs. In conclusion, supplementation with
      a high-dose of VIT E failed to protect maternal, foetal and new-born rat organs
      from PHT induced changes of selective biochemical variables.

PMID- 16601782
TI  - Effect of long-term administration of arsenic (III) and bromine with and without
      selenium and iodine supplementation on the element level in the thyroid of rat.
AB  - The aim of this study was to evaluate the influence of arsenic and bromine
      exposure with or without iodine and selenium supplementation on the element level
      in the thyroid of rats. Four major groups of Wistar female rats were fed with
      respective diets: group A - standard diet, group B - iodine rich diet (10 mg I/kg
      food), group C - selenium rich diet (1 mg Se/kg) and group D - iodine and
      selenium rich diet (as in group B and C). Each group was divided into four
      subgroups per 7 animals each receiving either NaAsO(2) ip (6.5 mg.kg(-1) twice a
      week for two weeks and 3.25 mg.kg(-1) for six weeks) or KBr in drinking water
      (58.8 mg.l(-1)) for 8 weeks or combined administration of both substances.
      Remaining subgroup served as controls. After 8 weeks thyroid glands were analyzed
      by ICP-MS for As, Br, Se, and I content. The exposition of rat to arsenic or
      bromine causes the accumulation of these elements in the thyroid gland (
      approximately 18 ppm of As, approximately 90 ppm of Br) and significantly affects
      iodine and selenium concentration in the thyroid. In iodine and/or selenium
      supplemented rats the bromine intake into the thyroid was lowered to
      approximately 50% of the level in unsupplemented animals. Also selenium thyroid
      level elevated due to KBr administration was lowered by iodine supplementation in
      the diet. The accumulation of arsenic in the thyroid was not influenced by
      selenium or iodine supplementation; however, As(III) administration increased
      iodine thyroid level and suppressed selenium thyroid level in selenium or iodine
      supplemented group of animals.

PMID- 16601783
TI  - Galantamine antiacetylcholinesterase activity in rat brain influenced by L
      carnitine.
AB  - Galantamine (GAL) is a selective, competitive and reversible acetylcholinesterase
      (AChE) inhibitor, which increases the activity of the cholinergic system and
      hence gives rise to an improvement of cognitive functions in patients suffering
      from dementia of Alzheimer type. L-Carnitine (CAR) is a natural component of the
      mammalian tissue and is known to increase penetration of some chemical
      compounds/groups across biological membranes. The aim of this study was to
      evaluate the influence of pretreatment with CAR on AChE inhibition caused by GAL
      in selected brain parts in rat (basal ganglia, septum, frontal cortex,
      hippocampus) and in hypophysis, which does not lay beyond the blood-brain
      barrier. During the first stage of the study, GAL was administered i.m. in
      different doses ranging from 2.5 to 10 mg/kg. The highest degree of AChE dose
      dependent inhibition was observed in hypophysis, while that in CNS was lower and
      became apparent in frontal cortex and hippocampus only after the administration
      of the dose of 10 mg/kg i.m. In the second stage, CAR was administered daily
      during 3 consecutive days at a dose of 250 mg/kg p.o. prior to the administration
      of GAL (10 mg/kg i.m.). Pretreatment with CAR enhanced trend of AChE inhibition
      in all selected brain parts comparing with single GAL administration, however,
      significant difference was not observed. Comparing these results with control
      group, statistical significance was found in frontal cortex, hippocampus and
      hypophysis.

PMID- 16601784
TI  - Effect of a new ultrashort betalytic agent on aconitine-induced arrhythmia.
AB  - The anti-arrhythmic effect was tested on the model of aconitine-induced
      arrhythmia. The experiment was performed in vivo with 31 male Wistar laboratory
      rats. Group A was first administered aconitine and, after the onset of the first
      sinus rhythm disorders, the 44Bu compound was administered. Group B was first
      administered the 44Bu compound and only after that the aconitine. The control
      group was administered aconitine and saline as a replacement of the tested
      compound. In group A, there was a decrease in the ventricular fibrillation
      occurrence from 100 % to 8 % (p < 0.001) after the administration of the 44Bu
      compound. In the B group, the onsets of all monitored arrhythmia types were
      delayed by an average of 15.6 min. Ventricular rhythm occurrence was decreased
      from 100 to 20 %, as well as ventricular fibrillations, from 100 to 0 % (p <
      0.001).

PMID- 16601785
TI  - Cytotoxicity and induction of apoptosis by 4-amino-3-acetylquinoline in murine
      leukemia cell line L1210.
AB  - Nitrogen heterocyclic compounds are used in the pharmaceutical industry, in
      medicine and in agriculture for their biological activity. 4-Amino-3
      acetylquinoline, a new synthetically prepared quinoline derivative, was the most
      effective compound in our primary cytotoxic screening. In this study, we
      evaluated cytotoxic/antiproliferative activity of quinoline using murine leukemia
      cell line L1210. Its ability to induce apoptosis was studied, too. Quinoline
      derivative acted cytotoxically on tumor cell line L1210, the IC(100) value were
      50 microg/ml (for 24 h), 25 microg/ml (for 48 h) and 10 microg/ml (for 72 h). The
      IC(50) values was found to be less than 4 microg/ml, a limit put forward by the
      National Cancer Institute (NCI) for classification of he compound as a potential
      anticancer drug. The cytotoxic concentrations of 4-amino-3-acetyl quinoline
      induced morphological changes of L1210 cells and the apoptotic DNA fragmentation.

PMID- 16601786
TI  - Interaction of aromatic cytokinins with human liver microsomal cytochromes P450.
AB  - Aromatic cytokinins (ortho-topolin riboside, 6-benzylaminopurine riboside and 6
      (2-hydroxy-3-methoxybenzyla mino)purine riboside) were tested for their possible
      interaction with human liver microsomal cytochromes P450 by absorption difference
      spectroscopy. All three compounds were shown to bind to the CYP enzymes producing
      a high to low spin shift of the heme iron yielding a Soret absorption band shift
      to approximately 425 nm. As this type of spectral change means that the substance
      is able to bind directly to the heme iron, the results obtained open the
      possibility of an interaction of these compounds with metabolism of other drugs
      or, in general, with other substrates of cytochromes P450.

PMID- 16601787
TI  - Comparison of "high throughput" micromethods for determination of cytochrome P450
      activities with classical methods using HPLC for product identification.
AB  - Enzyme activities of the CYP enzymes (CYP3A4, CYP2C9 and CYP2A6) were determined
      using classical substrates (testosterone, diclofenac and coumarin, respectively)
      as well as with luminogenic or fluorogenic substrates in micromethod arrangement.
      The luciferin-based luminogenic substrates for CYP3A4 and CYP2C9 as well as
      coumarin in micromethod for assay of CYP2A6 activity gave results well comparable
      with the classical methods with determination of reaction products by the HPLC.

PMID- 16601788
TI  - The effect of asbestos and stone-wool fibres on some chemokines and redox system
      of pulmonary alveolar macrophages and pneumocytes type II.
AB  - The in vitro effect of stone-wool has been studied in primary cultures of
      pulmonary alveolar macrophages (AM) and type II pneumocytes (T2) by
      morphological, biochemical and immunological methods. UICC crocidolite was
      applied as a positive control. Although stone-wool brought about frustrated
      phagocytosis, it did not induce serious membrane damage, whereas crocidolite gave
      rise to very severe membrane alterations. Stone-wool significantly reduced the
      activity of Cu,Zn/superoxide dismutase (SOD) in alveolar macrophages and
      significantly decreased the activity of gamma-glutamyl transpeptidase (GGT) in
      pneumocytes type II. Crocidolite, on the other hand, decreased the activity of
      all enzymes (glutathione peroxidase - GSH-Px, glutathione reductase - GSH-Rd) of
      glutathione metabolism in alveolar macrophages. It decreased the activity of all
      enzymes in pneumocytes type II except for Cu,Zn/SOD. After exposure to stone
      wool, the production of inflammatory proteins, macrophage chemoattractant protein
      1 (MCP-1) and macrophage inhibitory protein-1alpha (MIP-1alpha) increased in both
      cultured cells but did not reach the level induced by crocidolite. Although this
      study provided a useful insight in the toxicity of the stone-wool, we can not
      draw the conclusions how the intact pulmonary tissue may respond on the exposure
      to these fibres, exclusively based on the in vitro tests.

PMID- 16601789
TI  - Effect of intratracheal fibres exposure on the rat lung.
AB  - The changes in antioxidant status of rat lung after intratracheal instillation of
      stone-wool and glass fibres were studied. The animals were exposed to 2 or 8 mg
      of fibres for 4 or 16 weeks, the bronchoalveolar lavage was performed and the
      activity of superoxide dismutase, glutathione peroxidase and the total amount of
      glutathione was estimated both in tissue and in cell free fraction of
      bronchoalveolar lavage and the ascorbic acid was determined in lung tissue. The
      results showed the higher burden by stone-wool. Most changes were detected in
      groups exposed to higher dose of fibres for shorter time period, the most
      sensitive parameter was superoxide dismutase. The lung tissue was studied also by
      light microscopy and transmission electron microscopy.

PMID- 16601790
TI  - Influence of refractory ceramic fibres - asbestos substitute - on the selected
      parameters of bronchoalveolar lavage 6 months after intratracheal instillation to
      W-rats.
AB  - Industrial fibrous dusts are applied in many industrial branches and represent
      adverse factors in occupational and environmental area. Refractory ceramic fibers
      (RCFs) - amorphous alumina silicates - are used as one kind of asbestos
      substitutes. Because RCFs are relatively durable and some RCFs are respirable,
      they may present a potential health hazard by inhalation. The aim of present work
      was to find out the subchronic effect of RCFs on selected parameters of
      bronchoalveolar lavage (BAL) in W-rats, confirm the biopersistence of RCFs after
      6 month instillation and contribute to the understanding of the pathomechanism of
      lung injury after fibrous dust exposure. Wistar rats were intratracheally
      instilled with 4 mg/animal of RCFs - exposed group and with 0.4 ml saline
      solution/animal - control group. Animals were sacrificed after 6 month exposure.
      Bronchoalveolar lavage (BAL) was performed and selected BAL parameters (mainly
      inflammatory and cytotoxic) were examined. After treatment with RCFs the
      following changes were observed: statistically significant increase in proportion
      of lymphocytes and polymorphonuclears as well as in % of immature alveolar
      macrophages (AM) and phagocytic activity of AM; statistically significant
      decrease in viability of AM and proportion of AM (from the differential cell
      count) in comparison with the control group. The results of this study indicated
      that RCFs even 6 months after intratracheal instillation very significantly
      changed the majority of examined BAL parameters. The presence of inflammatory and
      cytotoxic response in lung may signalize beginning or developing disease process.

PMID- 16601791
TI  - New magnetic resonance spectroscopy biomarker for monitoring neurodegenerative
      diseases: animal models.
AB  - Creatine kinase (CK) plays a central role in energy transfer in cells with high
      energy demands, and the enzyme is rather susceptible to oxidative inactivation.
      The aim of the present study was to investigate whether the rate constant of
      forward CK reaction (k(for)) is a suitable indicator of alterations in cerebral
      energy metabolism. We monitored k(for) in the rat brain non-invasively by in vivo
      phosphorus ((31)P) magnetic resonance spectroscopy (MRS). To alter energy
      metabolism, we applied following experimental models: Huntington's disease,
      diabetes mellitus, chronic alcohol intoxication and chronic cerebral
      hypoperfusion (vascular dementia model). Results of our (31)P MRS experiment
      confirm importance of creatine kinase/phosphocreatinine (CK/PCr) system in the
      regulation of brain energy metabolism in vivo because a kinetic parameter k(for)
      was significantly changed in all above animal models that simulate
      neurodegenerative diseases or commonly during oxidative stress. Using this method
      we distinguished vascular dementia (VD) and Huntington disease (HD), because in
      VD model a kinetic parameter k(for) decreased and in the case HD increased.
      Considering the importance of CK for the maintenance of energy homeostasis in the
      brain, it is conceivable that an alteration of this enzyme activity in the brain
      may be one of the mechanisms by which various neurodegenerative diseases might be
      monitored just by means saturation transfer method (31)P MRS.

PMID- 16601792
TI  - Influence of antioxidant effect of stobadine derivative in condition of kidney
      ischemia-reperfusion in a pre-clinical experiment (effect in therapy).
AB  - The goal of the study was to monitor the antioxidative effect of stobadine
      derivative under conditions of ischemia-reperfusion of laboratory rat kidney
      tissue. 40 animals were subjected to kidney tissue ischemia (60 min) followed by
      reperfusion (10 min). After that, the animals were divided by random selection
      into 4 groups (n = 10). The treated groups were given stobadine derivative in
      peroral doses of 5, 10 and 20 mg/kg in 0.5% solution of Avicel once a day, the
      placebo group was given only the solution of Avicel. One group (n = 10) was an
      intact group (without ischemia-reperfusion and without treatment), for
      comparison. Once a week, selected laboratory parameters were determined in all
      animals. On the 15th day the animals were exsanquined and organs were recovered
      for histopathological examination. We discovered a statistically significant
      changes of the superoxiddismutase and glutathione peroxidase catalytic activity;
      changes of total antioxidative capacity and malondialdehyde in the treated groups
      compared to the groups of placebo and intact. Other examined laboratory
      parameters (creatinine, urea and uric acid in blood; creatinine, urea, total
      protein in urine; diuresis) exhibited significant changes too. The results of
      biochemical examination show a protective antioxidative effect of the compound
      studied. The results of histopathological examination support this assumption.

PMID- 16601793
TI  - Lung cytotoxicity of combined exposure to refractory ceramic fibres and cigarette
      smoke.
AB  - Changes in some lung cytotoxic parameters after exposure to refractory ceramic
      fibres (RCF) or to cigarette smoke (S) and after combined exposure to RCF+S were
      studied in male Wistar rats in order to evaluate their potential adverse health
      effects. Four groups of rats were treated as follows : 1) intratracheally
      instilled by saline solution (0.4 ml); 2) intratracheally instilled by 4 mg of
      RCF; 3) exposed only to S (85 mg of total particulate matter/m(3) air ) for two
      hours daily; 4) exposed to RCF+S. After 6 months the animals were exsanguinated
      and the bronchoalveolar lavage (BAL) was perfomed. Viability and phagocytic
      activity of alveolar macrophages (AM), activity of lactate dehydrogenase (LDH) in
      cell-free BAL fluid (cf-BALF), acid phosphatase (ACP) and cathepsin D (CATD) in
      cfBALF, in BALF cells and in the lung tissue were estimated. Viability of AM was
      depressed by every type of exposure with RCF+S effect being at least additive.
      Phagocytic activity of AM increased in the presence of RCF. No significant
      changes in LDH activity were found. Activities of lysosomal enzymes measured in
      the lung tissue homogenates were not significantly changed, but those in the
      cfBALF increased especially after exposure to S with most expressive increase in
      BALF cells after exposure to S and RCF+S. In the case of CATD the effect of RCF+S
      was more than additive. The results point out to the persistence of the RCF
      exposure cytotoxic effects and their amplification by cigarette smoke.

PMID- 16601794
TI  - Influence of antioxidant effect of stobadine derivative in condition of kidney
      ischemia-reperfusion in a pre-clinical experiment (effect in prophylaxis).
AB  - The goal of the study was to monitor the antioxidative effect of stobadine
      derivative in the conditions of ischemia-reperfusion of laboratory rat kidney
      tissue. The animals were divided by random selection into 5 groups (n = 10). The
      treated groups were given stobadine derivate in peroral doses of 5, 10 and 20
      mg/kg in 0.5 % solution of Avicel once a day; the placebo group was given only
      the solution of Avicel. The last group was an intact group (without ischemia
      reperfusion and without treatment). After conclusion of medication on the 15th
      day all animals were subjected to kidney tissue ischemia (60 min.) followed by
      reperfusion (10 min.). All animals were subsequently exsanquined and single
      identification of superoxiddismutase, glutathion peroxidase, total antioxidative
      capacity, and malondialdehyde level in the blood were determined. Kidneys were
      recovered for histopathological examination. A statistically significant decrease
      of the superoxiddismutase and statistically significant increase of the
      glutathione peroxidase catalytic activity in the treated groups compared to the
      groups of placebo and intact was discovered. There was also a statistically
      highly significant increase of total antioxidative capacity in the treated groups
      compared to the groups of placebo and intact. A statistically significant
      decrease of malondialdehyde level was identified in the treated groups compared
      to the groups of placebo and intact. The results of biochemical examination show
      a protective antioxidative effect of stobadine derivative. The results of
      histopathological examination support this assumption.

PMID- 16601795
TI  - Influence of carvedilol on superoxide generation and enzyme release from
      stimulated human neutrophils.
AB  - Activation of neutrophils induces generation of reactive oxygen species and
      release of granule enzymes, which not only participate in the bactericidal
      mechanisms of these cells, but also in possible tissue damage. We studied the
      effect of carvedilol (CARV) [0.1-100 micromol/l], an antihypertensive and
      cardiovascular drug with antioxidative properties, on superoxide generation (SO)
      and myeloperoxidase (MPO) release from isolated human neutrophils stimulated with
      fMLP, a specific receptor activator, or with PMA, a receptor bypassing stimulus.
      Unstimulated cells showed neither SO formation nor MPO release after
      preincubation with drug. CARV decreased fMLP and PMA stimulated MPO release and
      SO generation dose dependently. The inhibitory effect of CARV may attributed to
      non-specific action since its effect was not influenced by the type of
      stimulation. It might inhibit SO generation as well as MPO release either by
      membrane-operating stimulus (fMLP) or membrane bypassing activator (PMA).

PMID- 16601796
TI  - Comparison the cytotoxicity of hydroxyapatite measured by direct cell counting
      and MTT test in murine fibroblast NIH-3T3 cells.
AB  - The worldwide growing interest to biomaterials over the last years results from
      their irreplaceable role in medical clinic. Hydroxyapatite is used in bone
      reconstruction because of its similar chemical structure compared to the
      inorganic composition of human bone and it is basic building component of many
      newly prepared biomaterials. In this study, we evaluated
      cytotoxic/antiproliferative activity of hydroxyapatite extract using murine
      fibroblast cell line NIH-3T3 and two in vitro different cytotoxic assays: growth
      inhibition assay and MTT assay. Hydroxyapatite extract after 72 h of incubation
      manifested the significant in vitro cytotoxic/antiproliferative effect only at
      the highest concentration tested (100 %). The antiproliferative effect of
      hydroxyapatite extract at the other concentrations tested (75 %, 50 %, 25 %, 10
      %, 5 % and 1 %) was directly proportional to the concentration and the time of
      influence. The inhibition of cell proliferation was 86.8 - 0 %. The sensitivity
      of cell growth inhibition assay (direct counting of viable cells) to the extract
      influence was higher than that of MTT test.

PMID- 16601797
TI  - The effect of ceramic fibers on the immune system.
AB  - Male Sprague-Dawley rats were treated by intratracheal instillation with 1
      mg/animal of refractory ceramic fibers. Intratracheal exposure to ceramic fibers
      led to significant changes of immune response. Results of proliferative activity
      of spleen lymphocytes showed significantly decreased proliferative activity of T
      cells in response to mitogens phytohemagglutinin and concanavalin A in animals
      given ceramic fibers in comparison with control rats. Similarly, T-dependent B
      cell response to pokeweed mitogen was significantly suppressed. Spontaneous
      proliferative activity of lymphocytes in non-stimulated spleen cell cultures did
      not differ in exposed and control rats. No significant changes were found among
      groups in percentage of phagocytic blood polymorphonuclear leukocytes and
      percentage of cells with respiratory burst.

PMID- 16601798
TI  - Development of ciprofloxacin resistance due to chromosomal mutations induced by 2
      nitrofluorene.
AB  - In this paper we investigated the ability of 2-nitrofluorene to induce mutations
      leading to antibiotic resistance in quinolone-sensitive strain Salmonella
      typhimurium. After preincubation of bacteria with 2-nitrofluorene, the frequency
      of mutation to ciprofloxacin resistance was 57 fold higher than in the case of
      spontaneous mutability. Some of resultant resistant colonies showed a great
      increase of ciprofloxacin MIC.

PMID- 16601799
TI  - The effect of phenolic and polyphenolic compounds on the development of drug
      resistance.
AB  - The effect of two phenolic compounds vanillin (4-hydroxy-3-methoxybenzaldehyde)
      and lignin on the development of drug/antibiotic resistance in Salmonella
      typhimurium was studied. Using the modified Ames test we have shown that vanillin
      alone has negligible effect on spontaneous mutability to ciprofloxacin and
      gentamicin resistance. At the tested concentrations vanillin reduces the toxicity
      of 4-nitroquinoline-N-oxide (4NQO) and reduces the ability of this compound to
      induce mutations leading to ciprofloxacin but not to gentamicin resistance.
      Lignin at higher concentrations increases mutagenicity to ciprofloxacin
      resistance and possess considerable inhibition effect on the spontaneous and 4NQO
      induced mutability to gentamicin resistance.

PMID- 16601800
TI  - Delivery as "physiological stress" and its influence on liver enzymatic systems
      in asphyxial newborns.
AB  - A new aspect on delivery as "physiological stress" provides the possibility for
      assessing its influence in asphyxial newborns. Asphyxia is characterized by
      hypoxic ischemic damage of organs with subsequent damage due to reoxygenation and
      reperfusion. The aim of the study was to compare the activity of liver enzymatic
      systems of healthy newborns with asphyxial newborns. Reference values of the AST
      on the 1st day of life 0.80 +/- 0.12 microkat/l and on the 5th day of life 0.78
      +/- 0.11 microkat/l, of the ALT on the 1st day of life 0.29 +/- 0.04 microkat/l
      and on the 5th day of life 0.54 +/- 0.21 microkat/l and of the quotient of
      DeRitis on the 1(st) day of life 3.35 +/- 0.6 and on the 5th day of life 2.14 +/-
      0.22 were established. The quotient of DeRitis expresses better the influence of
      stress on healthy term newborns since isolated evaluation of liver enzymes and
      their dynamics, which is decreased on the 5th day of life shows stabilization of
      the baby and improvement of liver cell function in comparison with the 1st day of
      life. The authors found that delivery is considered to be a certain form of
      physiological stress.

PMID- 16601801
TI  - Involvement of glutathione in the cytotoxicity of 9-isothiocyanatoacridine.
AB  - Isothiocyanates (ITCs) are phytochemicals with promising cancer-preventive
      potential. To elucidate the mechanism of cytotoxicity of ITCs, their accumulation
      by cells and the role of intracellular glutathione, fluorescent 9
      isothiocyanatoacridine (AcITC) was synthesized. The kinetic parameters for the
      reactions of AcITC with thiols were estimated and the influence of AcITC on human
      chronic myeloid leukemia cell line (K562) in regard to intracellular glutathione
      was studied. Cytotoxicity was evaluated by MTT assay, IC(50)=29.2 +/- 2.5 microM
      (48 h incubation). This acridine derivative was able to induce apoptosis of cells
      (morphological changes of cells and DNA fragmentation were observed) at least
      within certain dose that only decreased the level of intracellular glutathione,
      excessive doses (completely depleted intracellular pool of glutathione) induced
      necrosis rather than apoptosis. Our results indicated that apoptosis of leukemia
      cells induced by ITC is possible only if intracellular glutathione is not
      entirely depleted.

PMID- 16601802
TI  - A comparison of the potency of trimedoxime and other currently available oximes
      to reactivate tabun-inhibited acetylcholinesterase and eliminate acute toxic
      effects of tabun.
AB  - Tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) belongs to highly toxic
      organophosphorus compounds misused as chemical warfare agents for military as
      well as terroristic purposes. It differs from other highly toxic organophosphates
      by its chemical structure and by the fact that tabun-inhibited
      acetylcholinesterase is extraordinarily difficult to reactivate. The potency of
      trimedoxime and other commonly used oximes (pralidoxime, obidoxime, the oxime HI
      6) to reactivate tabun-inhibited acetylcholinesterase and to eliminate tabun
      induced acute effects was evaluated using in vitro and in vivo methods. In vitro
      calculated kinetic parameters of reactivation of tabun-inhibited
      acetylcholinesterase from rat brain homogenate and in vivo determined percentage
      of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in
      poisoned rats show that trimedoxime seems to be the most efficacious reactivator
      in the case of tabun poisonings. Trimedoxime was also found to be the most
      efficacious oxime in the elimination of acute lethal toxic effects in tabun
      poisoned rats and mice. The oxime HI-6, so efficacious against soman, does not
      seem to be sufficiently effective oxime to reactivate tabun-inhibited
      acetylcholinesterase and to counteract acute lethal effects of tabun.

PMID- 16601803
TI  - Effectivity of new acetylcholinesterase reactivators in treatment of cyclosarin
      poisoning in mice and rats.
AB  - The present study was performed to assess and compare a therapeutic efficacy of
      obidoxime, HI-6, BI-6 and HS-6 administered in equimolar doses and combined with
      atropine in cyclosarin-poisoned mice and rats. It was demonstrated that all the
      therapeutic regimens tested, were able to decrease the cyclosarin-induced
      toxicity significantly - at least 1.5 times. Higher therapeutic ratios, almost
      three times, were achieved in rats in comparison with mice. The highest
      therapeutic ratio was achieved for therapeutic regimen consisting of HI-6 and
      atropine in both mice and rats. Obidoxime was the least effective oxime in the
      treatment of cyclosarin intoxication. The BI-6 oxime was significantly more
      efficacious than obidoxime (in both mice and rats) and HS-6 (in rats) but its
      effectiveness did not reach the efficacy of HI-6.

PMID- 16601804
TI  - Strategy for the development of new acetylcholinesterase reactivators - antidotes
      used for treatment of nerve agent poisonings.
AB  - The mechanism of intoxication with organophosphorus compounds, including highly
      toxic nerve agents, is based on the formation of irreversibly inhibited
      acetylcholinesterase (AChE; EC 3.1.1.7) that could be followed by a generalized
      cholinergic crisis. Nerve agent poisoning is conventionally treated using a
      combination of a cholinolytic drug (atropine mostly) to counteract the
      accumulation of acetylcholine at muscarinic receptors and AChE reactivators
      (pralidoxime or obidoxime) to reactivate inhibited AChE. At the Department of
      Toxicology, the strategy of the development of new more potent AChE reactivators
      consists of several steps: description of the nerve agent intoxication mechanism
      on the molecular basis (molecular design), prediction of the biological active
      structure of AChE reactivators (artificial neural networks), their synthesis, in
      vitro evaluation of their potencies (potentiometric titration and Ellman's
      method), in vivo studies (therapeutic index, LD(50) of newly synthesized
      reactivators, reactivation in different tissues, neuroprotective efficacy).

PMID- 16601805
TI  - Intestinal single-pass in situ perfusion technique in rat: the influence of L
      carnitine on absorption of 7-methoxytacrine.
AB  - 7-Methoxytacrine (7-MEOTA) is an acetylcholine-esterase inhibitor that is
      potentially useful in the therapy of some neurodegenerative disorders. L
      carnitine (CRT) is a naturally occuring compound that is known to increase
      penetration of some compounds through biological barriers. Aim of this study was
      how CRT influenced transintestinal absorption transport 7-MEOTA in rat using
      single-pass intestinal in situ perfusion method. The rate of absorption of 7
      MEOTA during luminal perfusion with single 7-MEOTA was compared with rate of
      absorption during simultaneous perfusion with 7-MEOTA and CRT and with absorption
      rate after the premedication with CRT for period of three days before beginning
      of perfusion. The methodical system was the perfusion of mesenterial bed (from
      arteria mesenterica superior to vena portae) and intestinal luminal perfusion
      (from duodenum to ileum). The lower transintestinal absorption in the course of
      simultaneously administration of CRT than just in case of perfusion with single 7
      MEOTA has been found. On the contrary a significantly higher absorption of 7
      MEOTA has been noted in group of rats premedicated with CRT for three consecutive
      days. The interpretation suggested that molecules of CRT incorporated into the
      metabolism of intestinal cells facilitated transport of 7-MEOTA (as a
      representative substance which is at least partly transferred by carrier
      mechanism). In case of simultaneous luminal perfusion with CRT and 7-MEOTA
      competitive over-saturation of carrier systems is probably.

PMID- 16601806
TI  - Antitumor drug ellipticine inhibits the activities of rat hepatic cytochromes
      P450.
AB  - Ellipticine is a potent antineoplastic agent, whose mode of action is considered
      to be based mainly on DNA intercalation and/or inhibition of topoisomerase II.
      Recently, we found that ellipticine also forms the cytochrome P450 (CYP)-mediated
      covalent DNA adducts. Here, we study the effect of ellipticine on CYP enzymes in
      rat hepatic microsomes, studying its binding to the enzymes and its potential to
      inhibit the CYP activities measured with their selective substrates. Although
      ellipticine was reported to be a selective and strong inhibitor of CYP1A1/2, we
      found that its inhibitory potential is non-specific. Ellipticine is the most
      potent inhibitor for CYP3A-dependent 6beta-hydroxylation of progesterone,
      followed by CYP1A1/2-dependent ethoxyresorufin O-deethylation and CYP2B-mediated
      pentoxyresorufin O-depentylation. Lower inhibition was detected for 1'
      hydroxylation of bufurarol, 21-hydroxylation of progesterone and 6-hydroxylation
      of chlorzoxazone catalyzed by CYP2D, CYP2C and CYP2E1, respectively. Ellipticine
      binds to several CYPs of rat hepatic microsomes. The binding titration of
      ellipticine typically give reverse type I spectrum with CYPs in rat hepatic
      microsomes. The results indicate that inhibition of CYPs by ellipticine cannot be
      explained only by its differential potency to bind to individual CYPs.

PMID- 16601807
TI  - Carcinogenic pollutants o-nitroanisole and o-anisidine are substrates and
      inducers of cytochromes P450.
AB  - 2-Methoxyaniline (o-anisidine) and 2-methoxynitrobenzene (o-nitroanisole) are
      important pollutants and potent carcinogens for rodents. o-Anisidine is oxidized
      by microsomes of rats and rabbits to N-(2-methoxyphenyl)hydroxylamine that is
      also formed as the reduction metabolite of o-nitroanisole. o-Anisidine is a
      promiscuity substrate of rat and rabbit cytochrome P450 (CYP) enzymes, because
      CYPs of 1A, 2B, 2E and 3A subfamilies oxidize o-anisidine. Using purified CYP
      enzymes, reconstituted with NADPH: CYP reductase, rabbit CYP2E1 was the most
      efficient enzyme oxidizing o-anisidine, but the ability of CYP1A1, 1A2, 2B2, 2B4
      and 3A6 to participate in o-anisidine oxidation was also proved. Utilizing
      Western blotting and consecutive immunoquantification employing chicken
      polyclonal anti bodies raised against various CYPs, the effect of o-anisidine and
      o-nitroanisole on the expression of the CYP enzymes was investigated. The
      expression of CYP1A1/2 was found to be strongly induced in rats treated with
      either compounds. In addition, 7-ethoxyresorufin O-deethylation, a marker
      activity for both CYP1A1 and 1A2, was significantly increased in rats treated
      with either carcinogen. The data demonstrate the participation of different rat
      and rabbit CYP enzymes in o-anisidine oxidation and indicate that both
      experimental animal species might serve as suitable models to mimic the o
      anisidine oxidation in human. Furthermore, by induction of rat hepatic and renal
      CYP1A1/2, both o-nitroanisole and o-anisidine influence their carcinogenic
      effects, modifying their detoxification and/or activation pathways.

PMID- 16601808
TI  - Oxidation of an antitumor drug ellipticine by peroxidases.
AB  - Ellipticine is a potent antineoplastic agent, whose mode of action is considered
      to be based mainly on DNA intercalation and/or inhibition of topoisomerase II.
      Since we found that ellipticine also forms the cytochrome P450 (CYP)-mediated
      covalent DNA adducts, this anticancer drug is considered to function as a pro
      drug, whose pharmacological efficiency and/or genotoxic side effects are
      dependent on its enzymatic activation in target tissues. Here, we demonstrate
      that ellipticine is also oxidized by peroxidases, which are abundantly expressed
      in several target tumor tissues. Lactoperoxidase, myeloperoxidase and horseradish
      peroxidase were used as models. Peroxidases in the presence of hydrogen peroxide
      oxidize ellipticine to an ellipticine dimer and N(2)-oxide of ellipticine as the
      major and minor metabolite, respectively. Inhibition of the peroxidase-mediated
      ellipticine oxidation by radical scavengers ascorbate, glutathione and NADH
      suggests a one-electron mechanism of the oxidation. The implication of the
      oxidation of ellipticine by peroxidases in its mechanism of action is discussed.

PMID- 16601809
TI  - Cytotoxicity and detection of damage to DNA by 3-(5-nitro-2-thienyl)-9-chloro-5
      morpholin-4-yl[1,2,4]triazolo[4,3-c] quinazoline on human cancer cell line HeLa.
AB  - Quinazolines - 1,3-benzodiazines are biological active compounds, which are used
      in the phamaceutical industry, in agriculture and in the medicine. As documented
      in the literature, many derivatives demonstrated anticancer activity and they act
      as multitarget agents. 3-(5-Nitro-2-thienyl)-9-chloro-5-morpholin-4
      yl[1,2,4]triazolo[4,3-c] quinazoline (NTCHMTQ) - a new synthetically prepared
      quinazoline derivative was the most effective derivative in our primary cytotoxic
      screening. In this study, we evaluated cytotoxic/antiproliferative activity of
      NTCHMTQ using human tumor cell line HeLa. Possible interaction of 3-(5-nitro-2
      thienyl)-9-chloro-5-morpholin-4-yl[1,2,4]triazolo[4,3-c] quinazoline with calf
      thymus DNA was tested by the DNA - modified screen - printed electrode.
      Quinazoline derivative acted cytotoxically on tumor cell line HeLa. The IC(100)
      value was 10 microg/ml. The IC(50) values was found to be less than 4 microg/ml,
      a limit put forward by the National Cancer Institute (NCI) for classification of
      he compound as a potential anticancer drug. Quinazoline at micromolar
      concentrations induced morphological changes and necrosis of HeLa cells. Using
      the DNA based electrochemical biosensor, we have not found damage to DNA under in
      vitro conditions at an incubation of the biosensor in mixture with quinazoline.

PMID- 16601810
TI  - Antiproliferative activity of berberine in vitro and in vivo.
AB  - Berberine, an isoquinoline plant alkaloid acted cytotoxically in vitro on tumour
      cell lines B16. Its anticancer activity in vivo was studied with the transplanted
      B16 line in the range of doses from 1 mg/kg to 10 mg/kg. The significant
      reduction of tumor volume was observed on day 16 at doses of 5 and 10 mg/kg. The
      dose of 1 mg/kg stimulated the tumor mass, but other tested concentration, 5 and
      10 mg/kg, reduced the tumor weight.

PMID- 16601811
TI  - Study on metabolites of 2,5-dimethoxy-4-bromamphetamine (DOB) in human urine
      using gas chromatography-mass spectrometry.
AB  - The study of the biotransformation of a new synthetic drug 2,5-dimethoxy-4
      bromamphetamine (DOB) and identification of its metabolites in urine of a
      poisoned person is described using gas chromatography mass spectrometry (GC-MS)
      with various ways of derivatization. It has been confirmed that one of its
      metabolic pathways leads to the corresponding 2-O-desmethyl and 5-O-desmethyl
      metabolites when the latter is prevailing. It is important to know the metabolism
      of this neurotoxic and hallucinogenic substance as it is a prerequisite for
      developing reliable toxicological diagnostic procedures and for assessment of
      toxicological risks.

PMID- 16601812
TI  - Possibilities and problems with identification and determination of "new"
      hypnotics.
AB  - Authors discuss problems with identification and determination of flunitrazepam
      and zolpidem in biological material (BM). Over the recent years, these two
      structurally different substances have become the most frequently used as well as
      abused hypnotic drugs. This study presents applicability of immunochemical
      methods in the screening of flunitrazepam, one of the most commonly prescribed
      drugs among the benzodiazepines. Herein described techniques, a liquid-liquid (L
      L) extraction, solid phase extraction (SPE) and the so-called "freeze out" method
      are used for isolation of the above mentioned compounds from BM. Besides the thin
      layer chromatography (TLC) and gas chromatography - mass spectrometry (GC-MS)
      applied in qualitative analysis, the study also describes a gas chromatography
      with electron capture detector (GC-ECD) and gas chromatography with nitrogen
      phosphorus detector (GC-NPD) optimized for the determination of flunitrazepam and
      zolpidem in blood (serum). Successful analyses of these two substances are of
      major importance, especially in interpreting the results of forensic
      toxicological examinations.

PMID- 16601813
TI  - Experiences of the Czech toxicological information centre with ethylene glycol
      poisoning.
AB  - The objective was to evaluate the severity of ethylene glycol (EG) intoxications
      in a 3-year retrospective study of the calls to the Toxicological Information
      Centre (TIC). Data about clinical course of patients with EG poisoning reported
      to the TIC in the years 2000-2002 were analysed. They were completed by the data
      from discharge records from the hospitals and by toxicological analyses. The chi
      square test, Student's t-test, Fisher's test and the calculation of linear
      correlation coefficient were used for statistical analysis. The significance
      level was set at 0.05. TIC received total 188 calls concerning EG, from which 33
      discharge reports were gained. There were 30 males (age 5-74 years) and 3 females
      (age 10-54 years). The patients ingested 252 ml on average (30-1000 ml); lethal
      dose (100 ml) was exceeded in 14 patients. Mean time interval from ingestion to
      admission was 3 hours (3-24 hours), mean length of hospitalisation 6 days (1-76
      days). Fourteen patients developed metabolic acidosis, nine unconsciousness,
      thirteen signs of nephrotoxicity and nine signs of hepatotoxicity. Three patients
      died. Antidote ethanol was given in 30 patients. Other treatment included
      haemodialysis (20 cases) and B vitamins (23 cases). Ingested dose and the time
      interval between ingestion and admission correlated with severity of kidney
      damage. These data confirm that EG poisoning could seriously threaten the life.
      Renal parameters were abnormal in 30 % of patients who were discharged from the
      hospital. Those patients will be followed to evaluate the reversibility of EG
      toxic kidney damage.

PMID- 16601814
TI  - Use of marijuana in pharmacy students (2000-2005).
AB  - In 2000-2005, a survey on the consumption of legal and illegal drugs of abuse was
      conducted in 1571 students of Faculty of Pharmacy in Hradec Kralove, Charles
      University in Prague. The availability of cannabis and the prevalence rates of
      its use in university students were investigated. A standardized anonymous
      questionnaire was employed for the survey. The average age of respondents was 20
      years. The number of females was higher (82.8 %) than that of males. Marijuana
      was the most available and the most commonly used illegal drug of abuse in the
      group of pharmacy students. Its offer and the life-time prevalence increased over
      the 5 year period of the survey from 55.8 % to 72.9 % and from 30.3 % to 48.4 %,
      respectively. There was a predominance of the male users over the female ones,
      mainly in a category of high frequency of marijuana consumption ("used more than
      five times"). Almost three quarters of marijuana consumers admitted more than one
      experience with marijuana. Our data provide worrying statistics and support the
      need of continuous education also in university students to advise them on the
      risks of drug misuse.

PMID- 16601815
TI  - Natural opium as one of the possibilities for drug abusers.
AB  - Natural opium is a popular seasonal alternation for substance dependent people.
      Its processing, way of using, experience and change of habits was the aim of our
      study carried out via anonymous questionnaire and directed interview. 47
      questionnaires were obtained. According to our results natural opium has been
      abused by people 19-42 years old, more than a half of them were male. Basic drug
      were pervitin in 57 %, marihuana in 33 %, a considerable part (30 %) was natural
      opium. Each grower produced approximately 35 g of raw opium in one season. The
      most frequent way of application was smoking, injecting and "opium tea" drinking.
      Almost a half of the clients (40 %) felt attenuation after application;
      relaxation, hallucination and central stimulation admitted 25 % of respondents.
      Health troubles had majority of the users. Combinations of natural opium with
      other drugs (alcohol, marihuana, pervitin) declared 45 % respondents, the effects
      of the combinations admitted one third of users. The examination for viral
      hepatitis confirmed more than a half of the clients; the major part of users from
      Olomouc, but only 25 % of users from Prostejov were tested for HIV. Opium
      consumption influenced habits of personal hygiene of more than a half of the
      users (57 %). Routine servicing of the spot of the needle insertion practiced a
      half of the responders. Majority of the abusers (79 %) obtained and closed out
      paraphernalia throw to the "harm reduction" program.

PMID- 16601816
TI  - Using of electrochemical methods for studying of metallothionein content in the
      human blood serum of a patient poisoned by lead and treated by platinum.
AB  - Metallothioneins belong to the group of intracellular, high molecular and
      cysteine-rich proteins whose content increase with increasing concentration of a
      heavy metal. Here we applied the adsorptive transfer stripping differential pulse
      voltammetry Brdicka reaction for the determination of metallothionein in human
      blood serum of patient poisoned by lead and/or treated by platinum. The increased
      metallothionein concentrations in both cases were observed.

PMID- 16601817
TI  - Antimutagenic effect of phenolic acids.
AB  - In the present study, the Salmonella typhimurium tester strain TA 100 was used in
      the plate-incorporation test to examine the antimutagenic potential of caffeic,
      ferulic and cichoric acids extracted from plant species of genera Echinacea (L)
      Moench, as well as of another phenolic acids, on 3-(5-nitro-2-furyl)acrylic acid
      (5NFAA) and sodium azide mutagenicity. All tested compounds possess antimutagenic
      activity. In the case of 5NFAA, the antimutagenic potency of tested compounds was
      in the order of gallic acid > ferulic acid > caffeic acid > syringic acid >
      vanillic acid. The mutagenic effect of sodium azide was inhibited by tested
      phenolic acids by about 20-35 %. The most effective compound, gallic acid
      inhibits this effect by 82 % in the concentration of 500 mug/plate. The only
      exception from favourable properties of tested phenolic acids is cichoric acid,
      which in the contrary significantly increased the mutagenic effect of 5NFAA.

PMID- 16601818
TI  - The role of natural biopolymers in genotoxicity of mutagens/carcinogens
      elimination.
AB  - Nowadays naturally occurring compounds with the potential antimutagenic and
      anticarcinogenic effects are of great importance for their prospective use in
      cancer chemoprevention and treatment. The new water soluble derivative of
      microbial polysaccharide beta-D-glucan-carboxymethyl glucan (CMG) belongs to such
      a category of natural substances. CMG isolated from the cell wall of baker's
      yeast Saccharomyces cerevisiae is included into the class of biopolymers known as
      biological response modifiers (BRMs) with a broad range of activities, above all
      ones interfering with cancer therapy. It was demonstrated on four experimental
      model systems that biological and consequential medicinal importance of CMG is
      based on the combined application with another active compound. In the
      Saccharomyces cerevisiae antimutagenicity assay CMG significantly reduced
      ofloxacin-induced mutagenicity in the yeast strain D7. CMG exerted bioprotective
      (anti-toxic and antimutagenic) effect after its simultaneos application with
      methyl methanesulphonate on the repair-deficient strain uvs10 of the unicellular
      green alga Chlamydomonas reinhardtii. In the Vicia sativa simultaneous
      phytotoxicity and anticlastogenicity assay CMG exerted statistically significant
      anticlastogenic efect against maleic hydrazide-induced clastogenicity in Vicia
      sativa L. Only in the Salmonella/microsome assay CMG did not exert statistically
      significant antigenotoxic effect, despite of the fact that it reduced 9
      aminoacridine-induced mutagenicity in S. typhimurium TA97, but his(+) revertants
      decreasing was statistically significant only at the highest CMG concentration
      used. The data presented unambiguously documented that even biopolysaccharides
      (e.g., derivatives of beta-glucan) belonging to the most abundant class of
      natural biopolymers may contribute to cancer prevention and therapy.

PMID- 16601819
TI  - The effect of quercetin and galangin on glutathione reductase.
AB  - Quercetin and galangin can change the activity of glutathione reductase.
      Quercetin (a catechol structure in the B-ring) and galangin (any hydroxyl group
      in the B-ring) have different biological activities but, both possess high
      antioxidant abilities. Quercetin during the antioxidative action, is converted
      into an oxidized products (o-semiquinone and o-quinone), and subsequently
      glutathionyl adducts may be formed or SH-enzyme can be inhibited. We have tried
      to see whether inhibition of glutathione reductase (GR) can be influenced by
      preincubation of enzyme with NADPH (a creation of reduced form of enzyme, GRH(2))
      and whether diaphorase activity of the enzyme is decreased by these flavonoids.
      The results confirmed that quercetin inhibits GRH(2) and inhibition is reduced by
      addition of EDTA or N-acetylcysteine. Both of flavonoids have no effect on
      diaphorase activity of glutathione reductase and this enzyme could increase the
      production of free radicals by catalysis of reduction of o-quinone during action
      of quercetin in vivo.

PMID- 16601820
TI  - Effect of coenzyme Q(10) supplementation in the rat model of adjuvant arthritis.
AB  - Adjuvant arthritis (AA) is a model of chronic inflammation induced by
      Mycobacterium butyricum and characterized by similar pathophysiological and
      pathobiochemical changes as rheumatoid arthritis (RA) in humans. In this study
      the antirheumatic activity of coenzyme Q(10) supplementation was tested not only
      as to its capability to suppress the inflammation edema of the hind paw and to
      improve the body weight of the arthritic animals, but also to improve so
      important biochemical parameters as markers of inflammation and oxidative stress,
      and of mitochondrial bioenergetics. Despite the unfavorable effects on the
      rheumatic processes observed by monitoring biometric parameters (hind paw volume,
      relative body weight, relative weight of spleen), a significant protective effect
      was observed on the level of mitochondrial energetic and antioxidant disbalance.
      This finding speaks in favor of CoQ(10) supplementation in rheumatic patients,
      presumably as combinatory therapy with classical antirheumatics, e.g. NSAIDs.

PMID- 16601821
TI  - The implications of electronic health record for personalized medicine.
AB  - The emerging concept of an electronic health record (EHR) targeted at a patient
      centric, cross-institutional and longitudinal information entity (possibly
      spanning the individuals lifetime) has great promise for personalized medicine.
      In fact, it is probably the only vehicle through which we may truly realize the
      personalization of medicine beyond population-based genetic profiles that are
      expected to become part of medication and treatment indications in the near
      future. The new EHR standards include mechanisms that integrate clinical data
      with genomic testing results obtained through applying research-type procedures,
      such as full DNA sequencing, to an individual patient. Although the most optimal
      process for the utilization of integrated clinical-genomic data in the EHR
      framework is still unclear, the new Health Level Seven (HL7) Clinical Genomics
      Draft Standard for Trial Use suggests using the 'encapsulate & bubble-up'
      approach, which includes two main phases: the encapsulation of raw genomic data
      and bubbling-up the most clinically significant portions of that data, while
      associating it with clinical phenotypes residing in the individual's EHR.

PMID- 16601822
TI  - The effect of print size on reading speed in dyslexia.
AB  - This article details a study which predicted that across a wide range of print
      sizes dyslexic reading would follow the same curve shape as skilled reading, with
      constant reading rates across large print sizes and a sharp decline in reading
      rates below a critical print size. It also predicted that dyslexic readers would
      require larger critical print sizes to attain their maximum reading speeds,
      following the letter position coding deficit hypothesis. Reading speed was
      measured across twelve print sizes ranging from Snellen equivalents of 20/12 to
      20/200 letter sizes for a group of dyslexic readers in Grades 2 to 4 (aged 7 to
      10 years), and for non-dyslexic readers in Grades 1 to 3 (aged 6 to 8 years). The
      groups were equated for word reading ability. Results confirmed that reading rate
      by-print size curves followed the same two-limbed shape for dyslexic and non
      dyslexic readers. Dyslexic reading curves showed higher critical print sizes and
      shallower reading rate-by-print size slopes below the critical print size,
      consistent with the hypothesis of a letter-position coding deficit. Non-dyslexic
      reading curves also showed a decrease of critical print size with age. A
      developmental lag model of dyslexic reading does not account for the results,
      since the regression of critical print size on maximum reading rate differed
      between groups.

PMID- 16601823
TI  - Density Functional Study of Mo-Carbonyl-Catalyzed Alkynol Cycloisomerization:
      Comparison with W-Catalyzed Reaction.
AB  - Mo-catalyzed endo-cycloisomerizations of alkynes tethered to alcohols have been
      studied using density functional theory, and comparisons were made with the W
      catalyzed reaction. The cycloisomerization is initiated with the formation of
      metal alkyne pi complex and is followed by the rate-determining step, which
      transforms the pi complex to a vinylidene carbene complex, considered to be
      critical for endo-mode cyclization. Several different alkynols have been selected
      to investigate five- and six-membered ring endo-cycloisomerizations in the
      presence of Mo(CO)(5) catalyst. The energy barriers calculated for five- and six
      membered ring cycloisomerizations are within a range of 25-30 kcal/mol for most
      cases studied, showing no significant energy difference between the two metals.
      The stabilization effect of THF and Et(3)N solvents and the substitution reaction
      of THF by alkynol substrates in the reaction process with Mo and W complexes are
      studied as well. The principal difference between Mo- and W-catalyzed
      cycloisomerization processes appears to be the initial formation of a pi complex,
      which is more stabilizing for formation of the W-alkyne vs Mo-alkyne complexes.

PMID- 16601825
TI  - [Argentine consensus on the treatment of bipolar disorders].
AB  - The consensus guidelines of argentine experts in the treatment of bipolar
      disorders are the result of three days of work of the 10 main local experts under
      the organization of the Argentine Association of Biological Psychiatry (AAPB). It
      was adopted a mixed criterion for its preparation: all the recent data of the
      evidence medicine based published until now were discussed and were balanced with
      the knowledge acquired from clinical experience of the local experts on the
      bipolar field. It presents general recommendations and suggested therapeutic
      sequences for the phase of maintenance, the manic/hypomanic or mixed episode and
      the depressive episode. These have been divided according to the classification
      in type I and II; with or without rapid cycling. Since the group of experts
      identified the delay and miss-diagnoses like the most important barrier for a
      suitable treatment enclosed a series of recommendations for differential
      diagnosis of bipolar disorders.

PMID- 16601826
TI  - NO-synthase inhibition in sepsis.

PMID- 16601824
TI  - THE RELATIONSHIP BETWEEN ACUTE GLUCOCORTICOID LEVELS AND HIPPOCAMPAL FUNCTION
      DEPENDS UPON TASK AVERSIVENESS AND MEMORY PROCESSING STAGE.
AB  - This review evaluates the effects of glucocorticoids (GCs), the adrenal steroids
      released in response to stress, on memory functions requiring the hippocampus in
      animals and humans. The data support the hypothesis that the learning function
      between GCs and hippocampal-dependent memory is modulated by 1) the aversive
      nature of the learning paradigm and 2) stage of memory processing (acquisition,
      consolidation, retrieval). When tasks are minimally aversive, the glucocorticoid
      receptor (GR) mediates an inverted U-shaped relationship between GC levels and
      hippocampal function, while the mineralocorticoid receptor (MR) mediates
      attentional processes and/or reaction to novelty. This inverted U-shaped
      relationship during minimally aversive training paradigms describes GC-mediated
      memory processing at both acquisition and consolidation. In contrast, highly
      aversive paradigms activate the amygdala and elevate GCs as part of the training
      procedure, revealing a nonlinear inverted U-shaped relationship during
      acquisition and a positive linear function during consolidation. Thus, highly
      aversive tasks that activate the amygdala shift the memory function from an
      inverted U-shaped curve to a linear representation between GC levels and memory
      consolidation.

PMID- 16601827
TI  - Characterisation of 96 mutations in 128 unrelated severe haemophilia A patients
      from France. Description of 62 novel mutations.
AB  - Direct sequencing of the coding region of factor VIII (F8) gene was used to
      determine the mutations responsible for severe haemophilia A (FVIII<1%) in 128
      unrelated haemophiliacs A, negative for intron 22 and intron 1 inversions. A
      mutation was found in 122/128 patients (95%). Ninety-six distinct mutations were
      identified in this cohort, 62 of these are novel. They consisted of deletions (7
      large and 24 small deletions), insertions (n = 9), associations of
      insertion/deletion (n = 2), association of deletion/substitution (n = 1), and
      single nucleotide substitutions (53 point mutations consisting of 31 missense, 20
      nonsense, and 2 splicing mutations). Twenty-two patients had developed
      inhibitors, and among this subgroup 3 large deletions, 6 frameshift, 9 nonsense
      and 4 missense mutations were detected. For 6 patients, among which one developed
      an anti-FVIII inhibitor, no mutations were detected in the coding and splicing
      regions of factor VIII gene. Different approaches of molecular modelling were
      performed in addition to familial linkage analysis to determine the
      pathophysiological responsibility of these novel missense mutations.

PMID- 16601828
TI  - Home treatment of haemarthroses using a single dose regimen of recombinant
      activated factor VII in patients with haemophilia and inhibitors. A multi-centre,
      randomised, double-blind, cross-over trial.
AB  - The aim was to evaluate the efficacy and safety of two recombinant factor VIIa
      (rFVIIa) dose regimens for treating haemarthroses in patients with congenital
      haemophilia A or B and inhibitors. This was a multicentre, randomised, cross
      over, double-blind trial. Patients were randomly allocated to treat a first joint
      bleeding episode with one 270 microg/kg rFVIIa dose followed by two doses of
      placebo at 3-hour intervals and a second joint bleed with three single doses of
      90 microg/kg rFVIIa at 3-hour intervals, or vice versa. Efficacy was evaluated
      using a novel and robust treatment response-rating scale based on patient
      assessment of pain and joint mobility. Outcome was rated at different timepoints,
      and an effective or ineffective treatment response was determined. Treatment
      "preference" was defined as effective treatment with one regimen and ineffective
      with the other. Patients with equally effective or ineffective treatments had no
      "preference". Treatment was rated as effective for 65% of patients using the 270
      microg/kg dose versus 70% for the 90 microg/kg x 3 regimen. An equal "preference"
      was noted for the two regimens (21% for each; p = 0.637); most patients (58%) had
      no "preference". 37/42 bleeding episodes (88%) were successfully treated with
      rFVIIa; additional haemostatic medications were administered for five episodes.
      No safety issues were identified. Administration of rFVIIa as a single 270
      microg/kg dose to treat haemarthroses in patients with haemophilia and inhibitors
      was at least as efficacious and safe as the 90 microg/kg x 3 regimen.

PMID- 16601829
TI  - Hyperprothrombinaemia-induced APC resistance: differential influence on fibrin
      formation and fibrinolysis.
AB  - The prothrombin gene mutation G20210A is a common risk factor for thrombosis and
      has been reported to cause APC resistance. However, the inhibition of thrombin
      formation by APC not only limits fibrin formation but also stimulates
      fibrinolysis by reducing TAFI activation. We evaluated the influence of
      prothrombin G20210A mutation on the anticoagulant and fibrinolytic activities of
      APC (1 microg/ml). Thirty-two heterozygous carriers and 32 non carriers were
      studied. APC anticoagulant activity was assessed by aPTT prolongation whereas APC
      fibrinolytic activity was determined by a microplate clot lysis assay. APC
      induced aPTT prolongation was markedly less pronounced in carriers than in non
      carriers. On the contrary, fibrinolysis time was shortened by APC to a comparable
      extent in both groups. Accordingly, prothrombin levels were strongly correlated
      with APC-induced aPTT prolongation but not with APC-induced shortening of lysis
      time. The addition of purified prothrombin to normal plasma (final concentration
      150%) caused APC resistance in the clotting assay over the whole range of tested
      APC concentrations (0.125-1.5 microg/ml). In the fibrinolytic assay, instead,
      prothrombin supplementation made the sample resistant to low but not to high
      concentrations of APC (>0.5 microg/ml). Thrombin and TAFIa determination in the
      presence of 1 microg/ml APC revealed that hyperprothrombinemia, although capable
      of enhancing thrombin generation, was unable to induce detectable TAFIa
      formation. It is suggested that APC resistance caused by hyperprothrombinaemia
      does not translate in impaired fibrinolysis, at least in the presence of high APC
      levels, because the increase in thrombin formation is insufficient to activate
      the amount of TAFI required to inhibit plasminogen conversion. These data might
      help to better understand the relationship between thrombin formation and
      fibrinolysis down-regulation.

PMID- 16601830
TI  - Association of factor V gene polymorphisms (Leiden; Cambridge; Hong Kong and HR2
      haplotype) with recurrent idiopathic pregnancy loss in Tunisia. A case-control
      study.
AB  - Inherited thrombophilia has been shown to be linked with fetal loss. We performed
      a case-control study on the association between thrombosis-related polymorphisms
      in the factor V (FV) gene (Leiden, Cambridge, Hong Kong; HR2 haplotype) and
      idiopathic recurrent pregnancy loss (RPL) in Tunisian women. A total of 348 women
      with RPL, and 203 control women were studied, corresponding to 1,250 pregnancy
      losses and 1,200 successful pregnancies. FV Leiden was seen in 19.4% of patients
      (4.3% in the homozygous state) and in 5.5% of controls. The prevalence of the FV
      HR2 haplotype was similar in patients and controls, but with 7 homozygous
      patients for 1 control. FV Cambridge and Hong Kong were absent from both patients
      and controls. The study of all pregnancy losses evidenced that the frequency of
      the factor V Leiden polymorphism was zero in women who had mis-carried before 7
      weeks of gestation, and then sharply increased to a plateau. After categorization
      of pregnancy losses (before 8 weeks of gestation; weeks 8 and 9; weeks 10 to 12;
      from the 13th week of gestation onwards), heterozygous and homozygous factor V
      Leiden polymorphisms, and homozygous FV HR2 haplotype, were associated with
      significant and independent risks of pregnancy loss during weeks 8 and 9, which
      increased during weeks 10 to 12, then culminated after week 12. In Tunisian women
      with idiopathic RPL, factor V Leiden polymorphism and homozygous FV HR2 haplotype
      are not a risk factor for very early pregnancy loss, before 8 weeks of gestation,
      but are thereafter associated with significant clinical risks, which gradually
      increase from the 8th week onwards.

PMID- 16601831
TI  - Thrombophilic risk factors and homocysteine levels in Behcet's disease in eastern
      Spain and their association with thrombotic events.
AB  - Behcet's disease (BD) is a chronic inflammatory disorder in which thrombosis
      occurs in about 30% of patients. The prothrombotic mechanisms are unknown.
      Thrombophilic defects and hyperhomocysteinaemia may be involved in the
      pathogenesis of thrombotic events, although results have been controversial.
      Moreover, no information is available on this issue for eastern Spain. We studied
      the prevalence of inherited and acquired thrombophilic risk factors in 79
      patients with BD (43 men, 36 women) who had (n = 23) or did not have (n = 56)
      thrombosis, and in 84 healthy control subjects (42 men, 42 women). Risk factors
      examined were antithrombin, protein C and protein S levels, factor V Leiden, the
      prothrombin G20210A mutation, the methylenetetrahydrofolate reductase C677T
      polymorphism, and acquired thrombophilic risk factors, including anticardiolipin
      antibodies, lupus anticoagulant, and serum homocysteine levels. There were no
      differences between patients and controls in any of the parameters studied. When
      we studied BD patients with and without thrombotic events, the only thrombophilic
      defect that differed was the prothrombin G20210A mutation: Three out of 23
      patients with thrombosis were carriers, compared with none of 56 patients without
      thrombosis (p = 0.022). Two of the three carriers developed catastrophic or
      recurrent thrombotic episodes; one was a homozygous carrier of the G20210A
      prothrombin mutation and the other was doubly heterozygous for the G20210A
      prothrombin mutation and factor V Leiden. A meta-analysis demonstrated an
      association of factor V Leiden and prothrombin mutation with thrombosis in BD.
      When studies from Turkey were excluded from the meta-analysis, only the
      prothrombin G20210A mutation was associated with thrombosis.

PMID- 16601832
TI  - Homocysteine levels in amniotic fluid. Relationship with birth-weight.
AB  - Hyperhomocysteinemia could play a similar role in the placenta to that played in
      adults at risk of thrombosis. Moreover, hyperhomocysteinemia in women is
      described to be associated with the birth of small for gestational age (SGA)
      newborns, although there are discrepancies on this issue. To date, there is no
      biochemical marker predictive of SGA in a given pregnancy. We verified the
      presence of a relationship between homocysteine in amniotic fluid at mid
      pregnancy and birth-weight. Amniotic fluid was obtained from 459 healthy women
      undergoing midtrimester amniocentesis (17.1 +/- 1.2 weeks) because of maternal
      age. Homocysteine levels were measured in 434 (10 twin) pregnancies. In addition,
      femur length (FL) and biparietal diameter (BPD) were measured. Outcome of
      pregnancy was recorded. 233 (53.7%) foetuses were males, 201 (46.3%) females. The
      mean homocysteine concentration was 1.04 +/- 0.72 microM, (95% C.I. 0.43-2.41).
      An univariate analysis showed the presence of an association with gestational
      age, FL, BPD. A multiple linear regression showed that homocysteine levels were
      significantly associated with FL (p < 0.001) and BPD (p = 0.011). After excluding
      twin pregnancies, 31 newborns (7.3%) were classified as SGA. Mean birth-weight
      was 2390 g in SGA, whereas it was 3360 g in 393 adequate for gestational age
      (AGA) newborns (p < 0.001). The adjusted mean level of homocysteine was
      significantly lower in AGA (1.01 microM; 95% C.I: 0.94-1.08) than that recorded
      in pregnancies resulting in a SGA (1.29 microM; 95% CI: 1.05-1.51; p = 0.03). In
      a large setting, these data provide reference values for homocysteine in amniotic
      fluids. Moreover, they suggest that homocysteine levels in amniotic fluids may be
      higher in pregnancies with a SGA newborn.

PMID- 16601833
TI  - Biodistribution of covalent antithrombin-heparin complexes.
AB  - We have developed a covalent antithrombin-heparin (ATH) complex with advantages
      compared to non-covalent antithrombin:heparin (AT:H) mixtures. In addition to
      increased activity, ATH has a longer intravenous half-life that is partly due to
      reduced plasma protein binding. Given ATH's altered clearance, we investigated
      biodistribution of ATH in vivo. ATH made from either human plasma-derived AT
      (pATH) or recombinant human (produced in goats) AT (rhATH) was studied. 125I-ATH
      + unlabeled carrier was injected into rabbits at different doses. 131I-labeled
      albumin was administered just before sacrifice as a marker for trapped blood in
      tissues. Immediately after sacrifice, animal components were removed, weighed,
      and subsamples were counted for gamma-radioactivity. Percent recoveries of ATH in
      various organs/compartments at different time points were calculated, and kinetic
      distribution plots generated. At saturating doses, early disappearance of rhATH
      from the circulation was much faster than pATH. Co-incident with clearance, 26 +/
      3% of dose for rhATH was liver-associated compared to only 3.7 +/- 0.5% for pATH
      by 20 min. Also, at early time periods, >60% of all extravascular ATH was liver
      associated. Analysis of the vena cava and aorta suggested that vessel wall
      binding might also account for initial plasma loss of rhATH. By 24 h, most of
      pATH and rhATH were present as urinary degradation products (51 +/- 3% and 63 +/-
      8%, respectively). In summary, systemic elimination of ATH is greatly influenced
      by the form of AT in the complex, with liver uptake and degradation playing a
      major role.

PMID- 16601834
TI  - Less pronounced enhancement of thrombin-dependent inactivation of plasminogen
      activator inhibitor type 1 by low molecular weight heparin compared with
      unfractionated heparin.
AB  - Plasminogen activator inhibitor type 1 (PAI-1), the primary inhibitor of
      plasminogen activators, also forms high molecular weight complexes with either
      thrombin or factor Xa (FXa) in the presence of heparin, resulting in the loss of
      mutual activities of enzyme and inhibitor. We have proposed that the inactivation
      of PAI-1 by these activated coagulation factors is one of the mechanisms
      responsible for coagulation-associated enhancement of fibrinolysis. In the
      present study, we compared the effects of low molecular weight (LMW)- and
      unfractionated-heparin on the interaction between PAI-1 and either thrombin or
      FXa. Both types of heparin enhanced the inhibition of thrombin activity by PAI-1
      with a bell-shaped pattern, though the magnitude of the enhancement was
      significantly weaker with LMW-heparin. In FXa inhibition by PAI-1, only
      unfractionated-heparin enhanced the inhibition. In the presence of vitronectin
      (Vn), the inhibition of thrombin and FXa by PAI-1 was further promoted by both
      types of heparin but to a significantly lesser extent with LMW-heparin. We then
      analyzed the possible enhancing effect of heparin on tissue plasminogen activator
      (tPA)-induced fibrinolysis. As a consequence of thrombin-dependent inactivation
      of PAI-1, tPA-induced fibrin clot lysis time in the presence of PAI-1 was
      shortened by unfractionated-heparin as well as by LMW-heparin with lesser extent,
      which was further enhanced by Vn. Less pronounced enhancement of complex
      formation between thrombin and PAI-1 by LMW-heparin appeared to be directly
      related to the weaker potential of LMW-heparin in enhancing fibrinolysis and
      accelerating hemorrhagic tendency via neutralization of PAI-1 activity.

PMID- 16601835
TI  - Analysis of SAGE data in human platelets: features of the transcriptome in an
      anucleate cell.
AB  - A comprehensive SAGE (serial analysis of gene expression) library of purified
      human platelets was established. Twenty-five thousand (25,000) tags were
      sequenced, and after removal of mitochondrial tags, 12,609 (51%) non
      mitochondrial-derived tags remained, corresponding to 2,300 different transcripts
      with expression levels of up to 30,000 tags per million. This new, highly
      purified SAGE library of platelets is enriched in specific transcripts. The
      complexity in terms of tag distribution is similar to cells that are still able
      to replenish their mRNA pool by transcription. We show that our SAGE data are
      consistent with recently published microarray data but show further details of
      the platelet transcriptome, including (i) longer UTR regions and more stable
      folding in the enriched mRNAs, (ii) biologically interesting new candidate mRNAs
      that show regulatory elements, including elements for RNA stabilization or for
      translational control, and (iii) significant enrichment of specific, highly
      transcribed mRNAs compared to a battery of SAGE libraries from other tissues.
      Among several regulatory mRNA elements known to be involved in mRNA localization
      and translational control, CPE elements are in particular enriched in the
      platelet transcriptome. mRNAs previously reported to be translationally regulated
      were found to be present in the library and were validated by real-time PCR.
      Furthermore, specific molecular functions such as signal transduction activity
      were found to be significantly enriched in the platelet transcriptome. These
      findings emphasize the richness and diversity of the platelet transcriptome.

PMID- 16601836
TI  - Dose- and time-dependent antiplatelet effects of aspirin.
AB  - Aspirin is widely used, but dosages in different clinical situations and the
      possible importance of "aspirin resistance" are debated. We performed an open
      cross-over study comparing no treatment (baseline) with three aspirin dosage
      regimens--37.5 mg/day for 10 days, 320 mg/day for 7 days, and, finally, a single
      640 mg dose (cumulative dose 960 mg)--in 15 healthy male volunteers. Platelet
      aggregability was assessed in whole blood (WB) and platelet rich plasma (PRP).
      The urinary excretions of stable thromboxane (TxM) and prostacyclin (PGI-M)
      metabolites, and bleeding time were also measured. Platelet COX inhibition was
      nearly complete already at 37.5 mg aspirin daily, as evidenced by >98%
      suppression of serum thromboxane B2 and almost abolished arachidonic acid (AA)
      induced aggregation in PRP 2-6 h after dosing. Bleeding time was similarly
      prolonged by all dosages of aspirin. Once daily dosing was associated with
      considerable recovery of AA induced platelet aggregation in WB after 24 hours,
      even after 960 mg aspirin. Collagen induced aggregation in WB with normal
      extracellular calcium levels (hirudin anticoagulated) was inhibited <40% at all
      dosages. TxM excretion was incompletely suppressed, and increased <24 hours after
      the cumulative 960 mg dose. Aspirin treatment reduced PGI-M already at the lowest
      dosage (by approximately 25%), but PGI-M excretion and platelet aggregability
      were not correlated. Antiplatelet effects of aspirin are limited in WB with
      normal calcium levels. Since recovery of COX-dependent platelet aggregation
      occurred within 24 hours, once daily dosing of aspirin might be insufficient in
      patients with increased platelet turnover.

PMID- 16601837
TI  - The effect of tissue type-plasminogen activator deletion and associated
      fibrin(ogen) deposition on macrophage localization in peritoneal inflammation.
AB  - There are two plasminogen activators (PAs), urokinase type-PA (u-PA) and tissue
      type-PA (t-PA). While u-PA is considered to be involved in cellular migration and
      tissue remodeling and t-PA in fibrinolysis, this distinction is not always clear
      cut. With the use of u-PA and t-PA gene deficient mice (u-PA-/- and t-PA-/- mice,
      respectively) we have assessed the role of each PA in acute peritonitis. The
      cellular infiltrate in both thioglycolate- and antigen-induced peritoneal
      exudates was unaffected in u-PA-/- mice; in contrast, in t-PA-/- mice, the
      macrophage numbers, particularly of the Mac-1(hi) population, in the peritoneal
      cavity by day 4 were significantly reduced compared to wild-type mice. However,
      examination of the peritoneal wall revealed in fact increased numbers of
      macrophages adhering on/in the cavity lining at all time points studied; in
      addition, increased fibrin(ogen) staining was observed for these mice. The
      reduced macrophage numbers in the peritoneal cavities of t-PA-/- mice could be
      increased by administration of plasmin or t-PA prior to harvesting the
      thioglycolate-elicited exudates. These results suggest that t-PA and not u-PA is
      the PA controlling fibrinolysis in murine peritonitis. In its absence macrophages
      adhere to the accumulated fibrin(ogen) on/in the cavity wall lining, most likely
      via Mac-1 binding, thus affecting migration into and/or out of the peritoneal
      cavity. They also highlight the need to examine both the peritoneal cavity and
      wall in order to monitor accurately the extent of a peritoneal inflammatory
      reaction. Peritoneal inflammation in t-PA-/- mice represents a useful model to
      study the progression of intra-abdominal adhesions during surgery and clinical
      peritonitis.

PMID- 16601838
TI  - Anti-angiogenesis mediated by angiostatin K1-3, K1-4 and K1-4.5. Involvement of
      p53, FasL, AKT and mRNA deregulation.
AB  - The molecular mechanism mediated by multiple forms of angiostatin via acting on
      proliferating vascular endothelium remains elusive. To address whether three
      forms of angiostatin, K1-3, K1-4 or K1-4.5, utilized similar or distinct pathways
      to mediate anti-angiogenesis, we adopted an adenoviral expression system to
      express secretable angiostatin molecules for CM collection. The anti-angiogenic
      activity of K1-3, K1-4 or K1-4.5 was confirmed by using proliferation, migration,
      tube formation and apoptotic assays of human endothelial cells. These angiostatin
      molecules at comparable expression level inhibited various in vitro angiogenesis
      assays with some variations. Furthermore, K1-3, K1-4 or K1-4.5 increased the
      expression of p53 protein and its downstream effectors, enhanced FasL-mediated
      signaling pathways, and decreased activation of AKT. At least three different
      receptors, Fas, integrin alpha(v)beta3 and ATP synthase, were involved in the
      anti-angiogenic action of angiostatin molecules. Besides, the expression of 189
      genes at mRNA level was significantly altered by K1-3, K1-4 or K1-4.5. More than
      70% of these genes participate in growth, inflammation, apoptosis, migration and
      extracellular matrix. Taken together, K1-3, K1-4 and K1-4.5, regardless of the
      number of kringles in the angiostatin molecules, mediated anti-angiogenesis via
      mostly similar pathways. We are the first to demonstrate the involvement of DAPK1
      in the mediation of anti-angiogenesis by angiostatin.

PMID- 16601839
TI  - High urokinase expression contributes to the angiogenic properties of endothelial
      cells derived from circulating progenitors.
AB  - Endothelial progenitor cells (EPC) display a unique ability to repair vascular
      injury and promote neovascularization although the underlying molecular
      mechanisms remain poorly understood. Urokinase-type plasminogen activator (uPA)
      and its receptor (uPAR) play a critical role in cell migration and angiogenesis
      by facilitating proteolysis of extracellular matrix. The aim of the present study
      was to characterize the uPA/uPAR-dependent proteolytic potential of EPC outgrown
      from human umbilical cord blood and to analyze its contribution to their
      angiogenic properties in vitro. Cells derived from EPC (EPDC), presenting typical
      features of late outgrowth endothelial cells, were compared to mature endothelial
      cells, represented by human umbilical vein endothelial cells (HUVEC). Using
      quantitative flow cytometry, enzyme-linked immunosorbent assays and zymography,
      we demonstrated that EPDC displayed higher levels of uPA and uPAR. In conditioned
      culture media, uPA-dependent proteolytic activity was also found to be
      significantly increased in EPDC. This activity was paralleled by a higher
      secretion of pro-metalloproteinase-2 (pro-MMP-2). Inhibition of EPDC-associated
      uPA by monoclonal antibodies that block either uPA activity or receptor binding,
      significantly reduced proliferation, migration and capillary like tube formation.
      Moreover, tumor necrosis factor-alpha and vascular endothelial growth factor,
      known to be locally secreted in ischemic areas, further increased the proteolytic
      potential of EPDC by up-regulating uPA and uPAR expression respectively. The EPDC
      response to these factors was found to be more pronounced than that of HUVEC. In
      conclusion, these findings indicated that EPDC are characterized by high
      intrinsic uPA/uPAR-dependent proteolytic potential that could contribute to their
      invasive and angiogenic behaviour.

PMID- 16601840
TI  - Tenilsetam prevents early diabetic retinopathy without correcting pericyte loss.
AB  - Hyperglycemia-induced mitochondrial overproduction of reactive oxygen species
      leads to the activation of different biochemical pathways involved in endothelial
      damage of the diabetic retina. Tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone] is
      a dicarbonyl scavenger in the millimolar range and a transition metal ion
      chelator in the micromolar range. We tested its effect on experimental diabetic
      retinopathy, and on endothelial cell characteristics in vitro. Streptozotocin
      diabetic male Wistar rats (60 mg/kg BW) received 50 mg/kg BW tenilsetam (D-T) for
      36 weeks, or no treatment (D). The impact of tenilsetam (0-30 mM) on endothelial
      proliferation, apoptosis, sprouting, cytokine-induced leucocyte-endothelial
      interaction, and VEGF expression was tested in vitro. Tenilsetam did not affect
      glycemic control or body weight in diabetic animals. The 3.7 fold increase in
      acellular capillaries in diabetic rats [p < 0.001 vs. non-diabetic controls (N)]
      was reduced by 70% (p < 0.001) through treatment, but pericyte loss (D vs. N 
      33%; p < 0.001) remained unaffected. In vitro, tenilsetam inhibited endothelial
      proliferation at lower doses, while inducing apoptosis at high doses. Leucocyte
      adhesion was only inhibited at high doses. Sprouting angiogenesis of bovine
      retinal endothelial cells was promoted at lower doses (< or = 10 mM). At
      micromolar concentrations, endothelial VEGF expression was upregulated by 100%.
      Long-term treatment with the AGE-inhibitor and iron-chelating compound tenilsetam
      inhibits the formation of acellular capillaries without correcting pericyte loss.
      The compound has dose-dependent effects on endothelial cell function. These data
      suggest that, independent of known properties, tenilsetam shows important rescue
      functions on endothelial cells which could be useful for the treatment of early
      diabetic retinopathy.

PMID- 16601841
TI  - Genetic analysis of CAV1 gene in hypertension and metabolic syndrome.
AB  - Recently, we reported that the polymorphism 1132T>C (GenBank: AF519768.1) of the
      NOS3 gene was associated with susceptibility to metabolic syndrome (MS) in
      hypertensive patients. This suggests that other genes such as CAV1, whose product
      (CAV1) regulates eNOS activity, could also be related to this phenotype. In this
      work we investigated the following: i) whether CAV1 is a quantitative trait locus
      of clustering of atherothrombotic traits associated with MS; ii) whether CVA1 is
      associated with hypertension or MS in hypertensive patients; and iii) whether
      genetic interaction between NOS3 and CAV1 is involved in the susceptibility or
      protection to hypertension associated with MS. To carry out the study, we
      genotyped 285 randomly selected individuals and 175 hypertensive patients, all of
      them < or = 60 years old, with two polymorphisms of the CAV1 gene: the 22285 C>T
      and the 22375-22375 del AC (GenBank AF125348), and the 1132T>C polymorphism of
      the NOS3 gene. To perform sample genotyping, we used pyrosequencing and FRET
      techniques. The 22285 C-22375-22375 del (Cd) haplotype of CAV1 gene was
      associated with low levels of blood pressure in the general population. Moreover,
      it was a genetic protection factor against MS in hypertensive patients. In
      addition, we found no evidence of gene-gene interaction between NOS3 and CAV1
      genes with regard to that phenotype.

PMID- 16601842
TI  - Prothrombotic activity is associated with the anatomical as well as the
      functional severity of peripheral arterial occlusive disease.
AB  - The importance of prothrombotic activity in cardiovascular disease has been well
      established. However, limited data exist on the relationship between
      prothrombotic activity and the severity of peripheral arterial occlusive disease
      (PAD). The objective of the present study was to investigate the relationship
      between markers of haemostasis and the diagnostic measures of PAD: ankle-brachial
      index (ABI), maximum treadmill walking distance and angiographic score. In a
      cross-sectional study of 127 patients (mean age 66 years; 64% males) with
      angiographically verified PAD, fasting blood samples were drawn, and citrated
      plasma was obtained for determination of selected haemostatic variables: von
      Willebrand factor (vWF), thrombomodulin (sTM), thrombin-antithrombin complex
      (TAT), soluble tissue factor (sTF), tPA antigen (tPAag) and D-dimer were all
      significantly correlated with the angiographic score (p < 0.05 for all). D-dimer,
      tPAag and fibrinogen were inversely correlated with the maximum treadmill walking
      distance, (p < 0.0001, p < 0.04 and p < 0.05, respectively), whereas fibrinogen
      was the only variable correlating to ABI (r = -0.223, p < 0.05). After adjustment
      for relevant covariates, D-dimer and TAT remained statistically significantly
      associated with the angiographic score (p < 0.001), and fibrinogen was,
      independent of other risk factors, inversely related with both the maximum
      treadmill walking distance and the ABI (p < 0.01 for both). This rather large
      study in patients with PAD showed that plasma levels of D-dimer, TAT and
      fibrinogen significantly predicted the extent of atherosclerosis, evaluated by
      angiographic score, maximum treadmill walking distance and ABI, respectively.
      These findings demonstrate a prothrombotic state in PAD patients, which might be
      of importance in future diagnosis and treatment of the disease.

PMID- 16601843
TI  - Interleukin-4 differentially regulates osteoprotegerin expression and induces
      calcification in vascular smooth muscle cells.
AB  - Vascular calcification is characterized by cellular transdifferentiation and
      expression of bone-related matrix proteins that result in the presence of bone
      like structures in the vascular wall. Interleukin (IL)-4, a pleiotropic cytokine,
      and osteoprotegerin (OPG), an essential regulator of osteoclast biology, have
      both been linked to vascular disease. Here, we assessed the role of IL-4 and OPG
      in vascular calcification in vitro. IL-4 induced OPG mRNA levels and protein
      secretion by 5-fold in a dose- and time-dependent fashion in human coronary
      artery smooth muscle cells (CASMC). Activation of the transcription factor STAT6
      preceded IL-4-induced OPG expression, and blockade of IL-4-induced STAT6
      activation by the phospholipase C inhibitor D609 decreased OPG expression. Long
      term exposure of IL-4 for 4 weeks resulted in transformation of CASMC towards an
      osteoblastic phenotype, based on the expression of the transcription factor Cbfa1
      and increased mineral deposition. Notably, calcification of CASMC was inhibited
      by gene silencing of Cbfa1. During osteogenic transformation, IL-4 down-regulated
      OPG production in CASMC. IL-4 has differential effects in CASMC: While short-term
      exposure enhances OPG production through a STAT6-dependent mechanism, long-term
      exposure causes Cbfa1-dependent osteogenic transformation and a decreased
      production of OPG, an inhibitor of bone resorption.

PMID- 16601844
TI  - Clinical usefulness of D-dimer testing in cancer patients with suspected
      pulmonary embolism.
AB  - Limited data are available about the diagnostic value of D-dimer testing in
      cancer patients with clinically suspected pulmonary embolism (PE). Therefore, we
      evaluated i) the safety and clinical usefulness of an ELISA D-dimer test to rule
      out PE in cancer patients compared with non-cancer patients and ii) whether
      adopting a higher D-dimer cut-off value might increase the usefulness of D-dimer
      in cancer patients. We analysed data from two outcome studies which enrolled
      1,721 consecutive patients presenting in the emergency department with clinically
      suspected PE. Presence of an active malignancy was abstracted from the database.
      All patients underwent a sequential diagnostic work-up including an ELISA D-dimer
      test and a 3-month followup. Sensitivity and predictive value (NPV) were 100% in
      both cancer and non-cancer patients. PE was ruled out by a negative D-dimer test
      in 494/1,554 (32%) patients without cancer, and in 18/164 (11%) patients with a
      malignancy. At cut-off values varying from 500 to 900 microg/l, the sensitivity
      was unchanged (100%, 95% CI: 93% to 100%) and the specificity increased from 16%
      (95% CI: 11% to 24%) to 30% (95% CI: 22% to 39%). The 3-month thromboembolic risk
      was 0% (95% CI: 0% to 18%) in cancer patients with a negative D-dimer test. ELISA
      D-dimer appears safe to rule out pulmonary embolism in cancer patients but it is
      negative in only one of ten patients at the usual cut-off value. Increasing the
      cut-off value of D-dimer in cancer patients might increase the test's clinical
      usefulness.

PMID- 16601846
TI  - Comparison of three activated protein C resistance tests in the risk assessment
      of venous thrombosis in non-carriers of the factor V Leiden mutation.
AB  - Activated protein C resistance (APCR), measured using the original assay
      described by Dahlback, is a risk factor for venous thrombosis independent of the
      factor V Leiden (FVL) mutation. This assay is based on the activated partial
      thromboplastin time (APTT) after plasma exposure to activated protein C (APC). As
      this assay was sensitive to numerous interferences, new assays have been
      developed for FVL screening. The objectives of the study were to investigate the
      association of second generation assays for APCR with venous thrombosis in FVL
      non-carriers. One hundred ninety-seven subjects with a history of venous
      thrombosis and 211 controls were explored using 3 APCR assays, the original APTT
      based assay (test A), an APTT-based assay with factor V depleted plasma pre
      dilution (test B) and a direct factor X activation-based assay with the same pre
      dilution (test C). We found that subjects with results in the lowest quartile of
      the APTT-based assays are at increased risk, compared to those in the highest
      quartile (test A Odds Ratio = 6.39; 95% CI 3.23-12.63; test B OR = 2.72; 95% CI
      1.50-4.94). There was no significant risk increase associated with test C
      results. After adjusting for FVIII levels, the ORs of tests A and B were similar
      (test A OR = 3.22; 95% CI 1.47-7.08; test B OR = 3.10; 95% CI 1.54-6.21). In
      conclusion, APTT-based assays, but not direct factor X activation-based assays,
      effectively detect the risk for venous thrombosis independent of FVL. Pre
      dilution in factor V depleted plasma is an effective way to directly assess the
      risk independent of FVIII levels.

PMID- 16601845
TI  - Effect of nitric oxide synthase (NOS) inhibition on macro- and microcirculation
      in a model of rat endotoxic shock.
AB  - Treatment of hemodynamic instability in septic shock often demands the
      administration of vasopressor agents, although these may have deleterious effects
      on microcirculatory homeostasis. Inhibition of nitric oxide synthase (NOS) has
      been suggested as an alternative therapeutic approach, as NO formation may be
      excessively increased in sepsis. To compare the effects of epinephrine titration,
      non-selective NOS inhibition by L-NMMA and selective inhibition of inducible NOS
      (iNOS) by 1400W on hemodynamics and on the regulation of microcirculation in a
      rat model of endotoxic shock, we intravenously injected endotoxin (LPS) or saline
      to male Wistar rats and after 2 hours randomized LPS treated rats into four
      different groups that received either saline, norepinephrine, L-NMMA or 1400W (n
      = 6 per group). Three hours after LPS administration, rats presented with severe
      systemic arterial hypotension (64 +/- 3 vs. 115 +/- 4 mmHg, p < 0.001),
      unresponsiveness to volume treatment, lactate acidosis and a marked increase in
      plasmatic nitrite and nitrate levels (15 +/- 8 vs. 263 +/- 47 microM, p < 0.001).
      Measurement of the tissue oxygenation in the ileum mucosal layer by the Erlangen
      micro-lightguide spectrophotometer (EMPHO) technique demonstrated marked
      heterogeneity of hemoglobin saturation, with appearance of low oxygenated areas.
      Norepinephrine, usually stabilizing blood pressure (99 +/- 7 vs. 67 +/- 4 mmHg 60
      min after infusion, p < 0.01), increased lactate formation (7.9 +/- 0.2 vs. 3.7
      +/- 0.5 mM, p < 0.001) and drastically increased low oxygenated regions in the
      ileum mucosal layer. L-NMMA similarly increased blood pressure (92 +/- 6 vs. 67
      +/- 4 mmHg 60 min after infusion, p < 0.05), but did not enhance lactate
      acidosis. However, some further deterioration of mucosa oxygenation was again
      noted. 1400W forwarded stabilization of blood pressure (88 +/- 5 vs. 67 +/- 4
      mmHg 60 min after injection, p < 0.05), reduced plasmatic nitrite and nitrate
      levels similar to L-NMMA, without an aggravation of lactate acidosis. In
      addition, mucosal oxygenation did not deteriorate in response to this agent.
      Thereby, we conclude that in a rat model of endotoxic shock selective iNOS
      inhibitors are superior to non-specific NOS inhibitors and in particular to
      norepinephrine for the treatment of macro- and microcirculatory abnormalities in
      experimental septic shock.

PMID- 16601847
TI  - Acquired haemophilia A: successful treatment with immunosuppression,
      methylprednisolone pulses and oral cyclosporin.

PMID- 16601848
TI  - Hypofibrinogenaemia resulting from novel single nucleotide deletion at codon
      Bbeta58 (3404del A) associated with thrombotic stroke in infancy.

PMID- 16601849
TI  - Renal vein thrombosis and membranous glomerulopathy in a patient homozygote for
      factor V Leiden mutation: a mere coincidence?

PMID- 16601850
TI  - Different cut-off values for two D-dimer assays to exclude deep venous thrombosis
      in primary care.

PMID- 16601851
TI  - Haemophilia A, factor VIII intron 22 inversion screening using subcycling-PCR.

PMID- 16601852
TI  - Haemophilia A in a female caused by coincidence of a Swyer syndrome and a
      missense mutation in factor VIII gene.

PMID- 16601853
TI  - Alteration of ADAMTS13 antigen levels in patients with idiopathic thrombotic
      thrombocytopenic purpura, idiopathic thrombocytopenic purpura and systemic lupus
      erythematosus.

PMID- 16601854
TI  - Haemostatic function in subjects with mild subclinical hypothyroidism. The Tromso
      study.

PMID- 16601855
TI  - The extension of disease is associated to an increased risk of venous
      thromboembolism (VTE) in patients with gastrointestinal (GI) carcinoma.

PMID- 16601856
TI  - Adenocarcinoma in an ileoanal pouch formed for ulcerative colitis in a patient
      with primary sclerosing cholangitis and a liver transplant: report of a case and
      review of the literature.
AB  - This is a report of the first case of adenocarcinoma arising in an ileal pouch
      after proctocolectomy for ulcerative colitis in a patient who had also undergone
      orthotopic liver transplantation for primary sclerosing cholangitis. Previously
      reported cases of adenocarcinoma developing after formation of an ileoanal pouch
      are reviewed as is the evidence for neoplastic transformation of the ileal
      mucosa. The risk factors for the development of colorectal cancer in patients
      with ulcerative colitis and the possibility that these may be risk factors for
      the development of pouch malignancy are discussed. We conclude that this patient
      exemplifies a small group of patients who may be at increased risk of developing
      pouch malignancy and need endoscopic follow-up. There is also the need for longer
      term follow-up data to determine the risk of this rare and potentially
      devastating complication of restorative proctocolectomy.

PMID- 16601857
TI  - Resonance assignments of the complex between TraN and the C-terminal domain of
      TraO from the conjugative plasmid pKM101.

PMID- 16601858
TI  - 1H, 13C and 15N resonance assignments of SMP-1: a small myristoylated protein
      from Leishmania major.

PMID- 16601859
TI  - Resonance assignments of a repeated domain of the egg case silk from Nephila
      antipodiana.

PMID- 16601860
TI  - NMR assignment of region 655-775 of human MAN1.

PMID- 16601864
TI  - D-2-Hydroxyglutaric aciduria: unravelling the biochemical pathway and the genetic
      defect.
AB  - D-2-Hydroxyglutaric aciduria (D-2-HGA) is a neurometabolic inherited disorder
      first described in 1980. In the following years, it became clear that the
      clinical phenotype of the disease varies widely from severe neonatal to
      asymptomatic. However, the sparse biochemical knowledge made D-2-HGA a poorly
      understood disease. Much progress has been made in the last five years in various
      studies, revealing two human enzymes that play a role in the metabolism of D-2
      hydroxyglutarate (D-2-HG): hydroxyacid-oxoacid transhydrogenase (HOT) and D-2-HG
      dehydrogenase. HOT is expected to be responsible for the formation of D-2-HG,
      while D-2-HG dehydrogenase converts D-2-HG into 2-ketoglutarate. We demonstrated
      pathogenic mutations in the D2HGD gene in patients with D-2-HGA, helping to
      unravel the primary defect causing D-2-HGA. However, in approximately 50% of the
      patients with D-2-HGA examined, no pathogenic mutations have yet been found.

PMID- 16601865
TI  - Asymmetric dimethylarginine in homocystinuria due to cystathionine beta-synthase
      deficiency: relevance of renal function.
AB  - OBJECTIVE: Vascular disease is associated with increased plasma asymmetric
      dimethylarginine (ADMA) and homocysteine, and both are increased in renal
      failure. In cystathionine beta-synthase deficiency (CBS) there is severe
      hyperhomocysteinaemia, precocious vascular disease, and endothelial dysfunction.
      We investigated whether ADMA levels are elevated in CBS patients with and without
      renal impairment, and whether lowering plasma homocysteine also lowers ADMA.
      METHODS: We measured plasma homocysteine, arginine, asymmetric and symmetric
      dimethylarginines, nitrate + nitrite, creatinine and cystatin C in 23 CBS
      deficient patients and 24 age-matched controls. RESULTS: In the patients, nitrate
      + nitrite and the ratio L: -arginine/ADMA were markedly reduced (21.6 +/- 6.1 vs
      57.7 +/- 7.5 micromol/L and 132.9 +/- 24.7 vs 181.9 +/- 56.1, respectively, p <
      0.001 for both), reflecting endothelial dysfunction. Plasma ADMA for the group
      was moderately increased (0.55 +/- 0.08 vs 0.49 +/- 0.07 micromol/L, p = 0.018),
      but this was due to significantly higher levels than controls in only those 7 of
      the 23 patients who had elevated cystatin C levels (0.59 +/- 0.08 vs 0.49 +/-
      0.07 mg/L, p = 0.007). Posttreatment total homocysteine in patients varied widely
      (15-285, median 92 micromol/L), but was not correlated with ADMA or other
      measured variables. In three newly-diagnosed patients, marked reduction of total
      homocysteine during treatment produced minimal changes in ADMA. CONCLUSIONS: ADMA
      levels were significantly increased only in the CBS-deficient patients with
      elevated cystatin C levels, and not in those with normal renal function. The
      reported relationship between hyperhomocysteinaemia and ADMA may not be direct,
      but could be secondary to reduced renal function.

PMID- 16601863
TI  - Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: an overview.
AB  - Hyperhomocysteinaemia has been regarded as a new modifiable risk factor for
      atherosclerosis and vascular disease. Homocysteine is a branch-point intermediate
      of methionine metabolism, which can be further metabolised via two alternative
      pathways: degraded irreversibly through the transsulphuration pathway or
      remethylated to methionine by the remethylation pathway. Both pathways are B
      vitamin-dependent. Plasma homocysteine concentrations are determined by
      nongenetic and genetic factors. The metabolism of homocysteine, the role of B
      vitamins and the contribution of nongenetic and genetic determinants of
      homocysteine concentrations are reviewed. The mechanisms whereby homocysteine
      causes endothelial damage and vascular disease are not fully understood.
      Recently, a link has been postulated between homocysteine, or its intermediates,
      and an alterated DNA methylation pattern. The involvement of epigenetic
      mechanisms in the context of homocysteine and atherosclerosis, due to inhibition
      of transmethylation reactions, is briefly overviewed.

PMID- 16601866
TI  - The spectrum of phenylalanine variations under tetrahydrobiopterin load in
      subjects affected by phenylalanine hydroxylase deficiency.
AB  - A fall in blood phenylalanine (Phe) after tetrahydrobiopterin (BH(4))
      administration is a common trait in phenylalanine hydroxylase (PAH, EC 1.14.16.1)
      deficiency (McKusick 261600). To explore the extent and biological correlates of
      this phenomenon we studied: (a) the spectrum of BH(4) response in patients with
      PAH deficiency; (b) the variability of BH(4) response according to the severity
      of the biochemical phenotype; and (c) the variability of the response to BH(4) in
      subjects with the same genotype. Fifty PAH-deficient subjects (age 1 month-35
      years) were enrolled for the study (5 with mild hyperphenylalaninaemia (MHPHE),
      15 with mild phenylketonuria (MPKU) and 30 with classic phenylketonuria (CPKU)
      and underwent an identical schedule of blood samplings 24 h before and after oral
      BH(4) challenge (6(R)-BH4, 20 mg/kg per day), leaving Phe intake unchanged. The
      effect of BH(4) on blood Phe concentration was evaluated according to the percent
      decrease of Phe during the 24 h following the challenge (criterion a), and as
      variation exceeding the individual variability of blood Phe (criterion b). The
      number of BH(4)-responders according to criterion b was 31 (including all the 14
      detected by criterion a): 17 out of 30 CPKU (57%), 9 out of 15 MPKU (60%), and
      all the MHPHE subjects (chi(2) = 3.45, df = 2, p = 0.178). The effect of BH(4)
      showed a large interindividual variability unrelated to diagnostic
      classification, basal value of blood Phe, maximum percentage of Phe reduction,
      Phe intake, and genotype. Some inconsistencies were found in patients with
      identical genotype. The first responsive case homozygous for the severe R408W
      mutation was found. Two new mutations, Y387X and G352C, were identified (the
      former was BH(4)-responsive), and the responsiveness of three already reported
      mutations (R261Q, D338Y, T92I) was substantiated.

PMID- 16601867
TI  - Vitamin B12 and vitamin B6 supplementation is needed among adults with
      phenylketonuria (PKU).
AB  - Phenylketonuria (PKU) is caused by an autosomal recessive deficiency of the
      enzyme phelnylalanine hydroxylase leading to a failure to convert phenylalanine
      to tyrosine. To avoid irreversible neurological damage because of increased
      phenylalanine, treatment is instituted rapidly after birth. We examined 31 adult
      PKU patients living on a less protein-restricted diet. Theoretically, these PKU
      patients had an increased risk of developing vitamin B(12) and B(6) deficiency
      because of a limited intake of animal products. Besides laboratory tests (n = 31)
      we obtained clinical information (n = 30) and detailed information on food
      consumption (n = 28). Three-quarters of the patients had early biochemical signs
      of vitamin B(12) deficiency. In spite of a normal folate status, 9 (29%) had a
      plasma homocysteine above 12 micromol/L. In accord with these findings, the food
      questionnaires indicated that 11 (39%) patients received less than the
      recommended daily vitamin B(12), and 20 (71%) received less vitamin B(6) than
      recommended. A significant association was found between reduced vitamin B(12)
      intake and both reduced serum cobalamins (p = 0.04) and reduced serum
      transcobalamin saturation (p = 0.03). Eleven patients took a vitamin pill daily,
      and these patients had a significantly lower plasma homocysteine compared to the
      rest. The present study suggests that adult PKU patients were at increased risk
      of developing vitamin B(12) deficiency, and their intake of vitamin B(6) was
      below the recommended daily intake. In conclusion PKU patients need continuing
      dietary guidance throughout adult life, and considering the risks, costs and
      potential benefits, daily vitamin supplementation seems justified in these
      patients.

PMID- 16601868
TI  - Cardiomyopathy in tyrosinaemia type I is common but usually benign.
AB  - Tyrosinaemia type I (TTI) is an inherited multisystemic disorder of tyrosine
      metabolism. In addition to hepatic and renal involvement, cardiomyopathy is an
      important clinical manifestation. OBJECTIVE: To evaluate the incidence and
      outcome of cardiomyopathy in TTI. SUBJECTS AND METHODS: A retrospective study was
      performed of 20 consecutive children with TTI (12 male, 8 female) referred to a
      single centre between 1986 and 2002. All were initially treated with standard
      dietary therapy and, since 1992, with nitisinone. The indications for orthotopic
      liver transplantation (LT) changed during the study. Serial echocardiography was
      undertaken in all subjects. RESULTS: 9/20 (45%) children had an acute hepatic
      presentation. Five (25%) received dietary treatment followed by LT, and 14 (70%)
      were treated with nitisinone at presentation. 6/20 (30%) had cardiomyopathy at
      initial assessment, with interventricular septal hypertrophy being the commonest
      finding (5/6). Cardiomyopathy was significantly less common in those treated
      initially with nitisinone. After a median follow-up of 3.6 (0.45-13.5) years, 5/6
      (83%) had complete resolution of cardiomyopathy and 1/6 showed significant
      improvement. No child with a normal initial echocardiography subsequently
      developed cardiomyopathy. CONCLUSION: Cardiomyopathy is a common manifestation of
      TTI and it has a favourable long-term outcome. Children initially treated with
      nitisinone are less likely to develop this complication.

PMID- 16601869
TI  - Effect of docosahexaenoic acid administration on plasma lipid profile and
      metabolic parameters of children with methylmalonic acidaemia.
AB  - AIM: To evaluate the effect of administration of docosahexaenoic acid (DHA) on
      dyslipidaemia, plasma fatty acid composition and metabolic parameters of children
      with isolated methylmalonic acidaemia (MMA) (McKusick 25100). METHODS: Four
      children (3 male, 1 female) with MMA (mut(0)), participated in a crossover,
      randomized study of DHA administration (25 mg/kg per day, divided into three
      daily doses). The control group comprised 56 healthy children, aged 10+/- 2.7
      years, (51 male, 5 female), who were followed in our clinic owing to possible
      familial risk of cardiovascular disease. RESULTS: The comparison of plasma fatty
      acid composition of children with MMA versus control children demonstrated that
      the patients had significantly higher values for oleic acid (p = 0.004) and
      linolenic acid (p = 0.008). No differences were observed in the levels of DHA and
      arachidonic acid. Plasma concentrations of insulin, glycine, ammonia, total
      cholesterol and cholesterol fractions did not change with DHA administration. No
      significant changes were observed in urinary excretion of methylmalonic acid. As
      expected, the percentage of DHA and n-3 fatty acids in plasma increased
      significantly after therapy (p = 0.005 and 0.014, respectively). The most
      remarkable result was a decrease of plasma levels of triglycerides after DHA
      therapy (p = 0.014). CONCLUSION: As previously found in normal children, dietary
      supplementation with DHA decreases the triglyceride levels, normalizing the
      hypertriglyceridaemia of these children without any evidence of short-term
      adverse effects.

PMID- 16601870
TI  - A single-residue mutation, G203E, causes 3-hydroxy-3-methylglutaric aciduria by
      occluding the substrate channel in the 3D structural model of HMG-CoA lyase.
AB  - 3-Hydroxy-3-methylglutaric aciduria is a rare autosomal recessive genetic
      disorder that affects ketogenesis and leucine metabolism. The disease is caused
      by mutations in the gene coding for 3-hydroxy-3-methylglutaryl-coenzyme A lyase
      (HL). To date 26 different mutations have been described. A (betaalpha)(8) TIM
      barrel structure has been proposed for the protein, and almost all missense
      mutations identified so far localize in the beta sheets that define the inside
      cavity. We report an Italian patient who bears homozygously a novel HL mutation,
      c.608G > A (p. G203E) in beta sheet six. A structural model of the mutated
      protein suggests that glutamic acid 203 impedes catalysis by blocking the
      entrance to the inner cavity of the enzyme. Loss of functionality has been
      confirmed in expression studies in E. coli, which demonstrate that the G203E
      mutation completely abolishes enzyme activity. Beta sheet six and beta sheet two
      are the two protein regions that accumulate most missense mutations, indicating
      their importance in enzyme functionality. A model for the mechanism of enzyme
      function is proposed.

PMID- 16601871
TI  - Fatty acid oxidation in the human fetus: implications for fetal and adult
      disease.
AB  - Studies in the last few years have shown a remarkably high activity of fatty acid
      oxidation (FAO) enzymes in human placenta. We have recently shown mRNA expression
      as well as enzymatic activity of long-chain FAO enzymes in the human embryo and
      fetus. In this study we show activity of the FAO enzymes carnitine
      palmitoyltranferase 1, medium-chain acyl-CoA dehydrogenase and short-chain
      hydroxyacyl-CoA dehydrogenase in embryonic and fetal tissues. In addition, we
      show the presence of different acylcarnitines in fetal liver and kidney, which
      substantiates the notion that the mitochondrial FAO enzymes are not only present
      in human fetal tissues but also metabolically active. In a glucose-rich
      environment FAO might be necessary for additional ATP production from fatty
      acids, but also for the breakdown of fatty acids that are products of the
      turnover of membranes in the growing fetus. The importance of FAO in the human
      embryo and fetus is further stressed by the fact that a higher frequency of
      prematurity, intrauterine growth retardation, fetal morbidity and intrauterine
      death is noted in long-chain FAO defects. Furthermore, in animal studies,
      gestational loss during early embryonic development has been observed as a
      consequence of disturbed FAO. Finally, there are indications that regulation of
      activity of FAO during fetal development might not only be important for fetal
      life but may also have implications for health and disease in adulthood.

PMID- 16601872
TI  - The tandem mass spectrometry newborn screening experience in North Carolina: 1997
      2005.
AB  - North Carolina (NC) was the first US state to initiate universal tandem mass
      spectrometry (MS/MS) newborn screening. This began as a statewide pilot project
      in 1997 to determine the incidence and feasibility of screening for fatty acid
      oxidation, organic acid and selected amino acid disorders. The MS/MS analyses
      were done by a commercial laboratory and all follow-up and confirmatory testing
      was performed through the NC Newborn Screening (NBS) Program. In April 1999, the
      NC NBS Laboratory began the MS/MS analyses in-house. Between 28 July 1997 and 28
      July 2005, 944,078 infants were screened and 219 diagnoses were confirmed on
      newborns with elevated screening results, for an overall incidence of 1:4,300.
      Ninety-nine infants were identified with fatty acid oxidation disorders, 58 with
      organic acidaemias and 62 with aminoacidopathies. Medium-chain acyl-CoA
      dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency and
      disorders of phenylalanine metabolism were the most common disorders detected.
      Identification of affected infants has allowed retrospective testing of other
      family members, resulting in an additional 16 diagnoses. Seven neonates died from
      complications of their metabolic disorders/prematurity despite timely MS/MS
      screening. In addition, there were six infants who were not identified by
      elevated NBS results but who presented with symptoms later in infancy. The NC
      MS/MS NBS Program uses a two-tier system, categorizing results as either
      'borderline' or 'diagnostic' elevated, for both the cutoffs and follow-up
      protocol. Infants with an initial borderline result had only a repeat screen.
      Infants with a diagnostic or two borderline results were referred for
      confirmatory testing. The positive predictive value of the NC MS/MS NBS for those
      infants requiring confirmatory testing was 53% for 2003 and 2004. The success of
      the NC MS/MS NBS Program in identifying infants with metabolic disorders was
      dependent on a comprehensive follow-up protocol integrating the public health
      laboratory and the academic metabolic centres.

PMID- 16601873
TI  - Measurement of ATP production in mitochondrial disorders.
AB  - Mitochondrial diseases are a heterogeneous group of disorders caused by mutations
      in both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Mitochondrial disease
      leads to impaired respiratory chain function and reduced ATP production. The aim
      of this study was to compare disturbances in mitochondrial function by measuring
      ATP synthesis in fibroblasts derived from patients with nDNA and mtDNA defects.
      Skin fibroblasts derived from 22 patients with either nDNA-related disorders (n =
      8) or mtDNA-related disorders (n = 14) were analysed. ATP synthesis was markedly
      decreased in fibroblasts derived from patients with nDNA-related disorders but
      only variably so in patients with mtDNA mutations. In fibroblasts with the MELAS
      3243A > G mutation, ATP synthesis correlated with mutant load. We believe that
      the observed differences in ATP production between cell lines derived from
      patients with nDNA-related disorders and mtDNA-related disorders may help in the
      assessment of patients with undiagnosed mitochondrial disease. The clinical
      comparisons observed in patients with nDNA- and mtDNA-related disorders may be
      explained by differences in the disturbance of ATP synthesis measured in the two
      conditions.

PMID- 16601874
TI  - Enzyme replacement therapy and bony changes in Egyptian paediatric Gaucher
      disease patients.
AB  - BACKGROUND: In Gaucher disease, the infiltration of the bone marrow by
      glucocerebroside-laden macrophages (Gaucher cells) triggers a diverse pattern of
      skeletal disease that results in crippling complications. Reliable ascertainment
      of the severity and pattern of skeletal disease is essential to determine disease
      status and the response to enzyme replacement therapy (ERT). Although there is
      ample documentation of reversal of haematological and visceral disease by ERT,
      there is a paucity of data on skeletal response to ERT in children. AIM: To
      delineate the pattern of bone disease in children with Gaucher disease in Egypt
      and to evaluate its response to ERT. METHOD: Twenty-two children with Gaucher
      disease were treated with ERT. Phenotyping by clinical, laboratory and
      radiological criteria was performed at baseline and following 11.2 +/- 4 months
      of ERT. Genotyping for glucocerebrosidase (GBA) mutations was performed by gene
      sequencing, and genotype-phenotype correlations were performed.Results. Two
      thirds of the patients were from consanguineous pedigrees and 14/22 patients were
      homozygous or compound heterozygous for L444P and D409H mutations. Bone
      involvement was detected by plain radiology in 11 children (50%) and in 16 (73%)
      by magnetic resonance imaging (MRI). There was no correlation of severity of bone
      involvement and GBA genotype. ERT ameliorated bone disease: 10 of the 11 children
      with abnormal radiographic findings at baseline showed improvement in skeletal
      lesions; while 9/16 showed improvement of marrow disease by MRI. Radiographic
      sensitivity and specificity were 62% and 82% compared to MRI for detection of
      bone involvement in this patient population. At baseline, bone pain was present
      in 5 patients and ERT resulted in complete symptomatic remission in all of them.
      ERT was associated with significant improvement in growth parameters and
      amelioration of haematological and visceral involvement. CONCLUSION: Symptomatic
      and radiological skeletal disease is common in children with Gaucher disease in
      Egypt. MRI is the most accurate technique for detecting early skeletal
      involvement. There was no correlation between severity of skeletal involvement
      and GBA genotype. ERT was effective in ameliorating radiological manifestations
      of skeletal disease and achieving complete remission of bone pain.

PMID- 16601875
TI  - Psychological complications of patients with Gaucher disease.
AB  - The Minnesota Multiphasic Personality Inventory (MMPI-2) is commonly used in
      chronic illness and chronic pain populations to assess psychological functioning.
      We report the results of the first study employing the MMPI-2 to assess
      psychological aspects of patients with Gaucher disease, type I (GD) is an inborn
      error of metabolism with unique features as a chronic illness: the disorder often
      presents with mild symptoms, and is frequently diagnosed in later childhood or
      adulthood; the treatment is highly efficacious, but, that same treatment is
      intrusive and expensive and requires that patients restructure their work and
      personal schedules. In this study, 28 patients with GD completed the MMPI-2 and a
      background questionnaire. GD patients scored significantly higher than the MMPI-2
      normative sample on MMPI-2 scales of Validity (K), Hypochondriasis (Hs),
      Depression (D), Hysteria (Hy), Psychasthenia (Pt) and Schizophrenia (Sc).
      Individuals with elevated scores on the Hs, D and Hy scales tend to have somatic
      concerns and depressed mood. Under stress, they are likely to report physical
      symptoms. Elevated Pt and Sc scales suggest psychological turmoil and, possibly
      feelings of isolation. An elevated K scale indicates a tendency for individuals
      to deny psychopathology. The length of time the patient with GD had been on
      enzyme replacement therapy was not significantly related to any of the 13 MMPI-2
      scales. Cohorts of patients with chronic heart disease (CRHD) and cohorts of
      patients with chronic pain were utilized as comparative populations in this
      investigation. The elevated scores of the GD patients on MMPI-2 scales Hs, D and
      Hy were similar to those of the CRHD population. The chronic pain patients also
      showed elevations on MMPI-2 scales Hs, D and Hy, which were elevated in the GD
      patients; the elevations in the chronic pain patients were higher than those
      shown by the GD patients. We conclude that patients with GD exhibit moderate to
      severe psychological complications, similar to patients with other long-term
      chronic illnesses.

PMID- 16601876
TI  - Manifestations of Fabry disease in placental tissue.
AB  - Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of
      the lysosomal enzyme alpha-galactosidase A. Manifestations of the disease in
      placental tissue have been reported only twice. We report for the first time on
      the biochemical, histological and genetic features of two cases: placenta A
      derived from a mother heterozygous for Fabry disease who gave birth to a
      hemizygous son, and placenta B obtained from a healthy mother who carried a
      heterozygous daughter. Biopsies of placentae A, B and of four healthy controls
      were taken directly after birth. Assessment of alpha-galactosidase A (alpha-Gal)
      activity was performed both in fetal leukocytes (derived from umbilical cord
      blood) and in the biopsy specimens. The tissue was further examined by electron
      microscopy, immunohistochemistry and biochemical analysis for the presence of
      storage material (ceramide trihexoside (CTH)). In placenta A, characteristic
      zebra bodies reflecting accumulated storage material were seen in all biopsies
      evaluated. CTH values were markedly elevated as compared to the controls and
      alpha-Gal activity in both fetal leukocytes and placental tissue was very low.
      Placenta B showed no storage material at all. CTH values were within the control
      range. alpha-Gal activity ranged from intermediate to near normal; enzyme
      activity in fetal leukocytes was significantly decreased. As placental tissue is
      mainly derived from fetal cells, we may conclude that, in a boy suffering from
      Fabry disease, extensive storage of CTH is already present at birth. As
      complications develop only around the age of 10 years, it may be not the CTH
      itself but secondary processes that cause cellular and organ damage.

PMID- 16601878
TI  - Inefficient cleavage of palmitoyl-protein thioesterase (PPT) substrates by
      aminothiols: implications for treatment of infantile neuronal ceroid
      lipofuscinosis.
AB  - Infantile neuronal ceroid lipofuscinosis (INCL, also known as infantile Batten
      disease) is a devastating neurodegenerative disorder caused by deficiency in the
      lysosomal enzyme palmitoyl-protein thioesterase (PPT, or CLN1), which functions
      to remove long-chain fatty acids from cysteine residues in proteins. A previous
      study suggested that the drug cysteamine, a simple aminothiol used in the
      treatment of cystinosis, may have utility in the treatment of INCL. In the
      current study, we compared the catalytic rate constants for the conversion of
      palmitoyl-CoA (a PPT substrate) and cystine (which accumulates in cystinosis) by
      cysteamine. We found that while cysteamine can react with palmitoyl-CoA, the rate
      constant is 10(3)-fold less than the reaction with cystine. Structure-activity
      studies suggested that it is the thiolate ion that is reactive in the cleavage
      reaction and that the amino group probably facilitates lysosomal entry. A modest
      effect of cysteamine (and two related aminothiols, WR 1065 and
      dimethylaminoethanethiol, DMAET) on PPT substrate accumulation in INCL
      lymphoblasts was observed. However, at optimum concentration a paradoxical
      increase in saposin immunoreactivity was seen, indicating possible lysosomal
      dysfunction. Improvements are needed in the design of small molecules for the
      treatment of INCL disease.

PMID- 16601877
TI  - The effect of 12-month enzyme replacement therapy on myocardial perfusion in
      patients with Fabry disease.
AB  - Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder
      secondary to deficient alpha-galactosidase A activity which leads to the
      widespread accumulation of globotriaosylceramide (Gb(3)) and related
      glycosphingolipids, especially in vascular smooth-muscle and endothelial cells.
      We have recently shown that the myocardial perfusion reserve of Fabry patients is
      significantly decreased. Thus, in the present study we investigated, whether it
      can be improved with enzyme replacement therapy (ERT). Ten patients (7 male, 3
      female; mean age 34, range 19-49 years) with confirmed Fabry disease were
      approved for this uncontrolled, open-label study. Myocardial perfusion was
      measured at rest and during dipyridamole-induced hyperaemia by positron emission
      tomography and radiowater. Myocardial perfusion reserve was calculated as the
      ratio between maximal and resting perfusion. Perfusion measurements were
      performed before and after 6 and 12 months of ERT by recombinant human alpha
      galactosidase A (Fabrazyme, Genzyme). Plasma Gb(3) concentration decreased
      significantly and the patients reported that they felt better and suffered less
      pain after the ERT. However, neither resting or dipyridamole-stimulated
      myocardial perfusion nor myocardial perfusion reserve changed during the ERT.
      Pretreatment relative wall thickness correlated negatively with posttreatment
      changes in flow reserve (r = -0.76, p = 0.05) and positively with posttreatment
      changes in minimal coronary resistance (r = 0.80, p = 0.03). This study shows
      that 12 months of ERT does not improve myocardial perfusion reserve, although the
      plasma Gb(3) concentration decreases. However, individual variation in the
      response to therapy was large and the results suggest that the success of the
      therapy may depend on the degree of cardiac hypertrophy.

PMID- 16601879
TI  - Long-term outcome and neuroradiological findings of 31 patients with 6
      pyruvoyltetrahydropterin synthase deficiency.
AB  - Tetrahydrobiopterin (BH(4)) deficiency is an autosomal recessive disorder caused
      by enzyme defects in the biosynthesis or recycling of BH(4). Patients with BH(4)
      deficiency present with severe neurological signs and symptoms and require a
      different treatment from classical phenylketonuria. During the last 12 years, 31
      cases of BH(4) deficiency were identified in our department. They were all
      classified as 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. They were
      diagnosed at the ages of 2.5-48 months and treated with BH(4), L-dopa and 5
      hydroxytryptophan immediately after diagnosis. The average development quotients
      (DQ) at diagnosis and after treatment for more than 3 years were 53+/- 16, and
      78+/- 15, respectively. A significant negative correlation was observed between
      the level of the DQ and the age at which treatment was commenced (r = -0.751, p =
      0.002). Developmental profiles were uneven. Language, adaptability and at later
      age mathematics were particularly weak areas. Only two patients achieved a good
      performance in mathematics. Eleven patients who were treated with drugs from ages
      of 2.9-48 months had neuroradiological scanning. Computed tomography disclosed
      calcification in lentiform nuclei in one patient and magnetic resonance imaging
      disclosed delayed myelination and abnormal high intensity signal in cerebral
      white matter in all of them. Even though most of abnormalities were reversible,
      small patchy or spotted areas were still present on these regions after treatment
      for 10-46 months. In summary, our study supports the substantial efficacy of the
      current therapeutic approach in PTPS deficiency of normalizing amine
      neurotransmitters with three drugs as early as possible. For the first time,
      calcifications could be detected in patients with PTPS deficiency. Abnormalities
      in white matter on magnetic resonance imaging were not related to clinical
      manifestations and most were reversible.

PMID- 16601880
TI  - Genetic heterogeneity of the GLDC gene in 28 unrelated patients with glycine
      encephalopathy.
AB  - Glycine encephalopathy, or nonketotic hyperglycinaemia (NKH; Mckusick 238300) is
      a severe autosomal recessive disease due to a defect in the glycine cleavage
      system (GCS), which is a complex of four subunits: P-, T-, H- and L-proteins. A P
      protein (glycine decarboxylase or GLDC) deficiency was reported in about 80% of
      NKH patients. We performed mutation analysis of the complete coding sequence of
      the GLDC gene in 28 unrelated patients with neonatal NKH using denaturing high
      performance liquid chromatography (DHPLC) and sequencing. Forty different gene
      alterations were identified, confirming the large molecular heterogeneity of the
      GLDC gene. Eighteen alterations were clearly disease-causing: two large
      deletions, four one-base deletions (c.28delC, c.1175delC, c.2186delC,
      c.2422delA), one 1-base insertion (c.1002_1003insT), one 4-base insertion
      (c.1285_1286insCAAA), one insertion/deletion (c.2153_2155delinsTCCTGGTTTA), five
      nonsense mutations (p.E153X, p.R236X, p.E270X, p.R337X, p.R424X) and four splice
      site mutations (c.861+1G > T, c.1402-1C > G, c.2316-1G > A, c.2919+1G > A).
      Additionally, we identified one intronic mutation outside the consensus splice
      sites (c.2838+5G > A) and 21 nucleotide substitutions leading to amino acid
      change (including three previously described mutations: p.T269M, p.R461Q,
      p.G771R), the pathogenicity of which should be confirmed by expression studies
      (p.S132W, p.Y138F, p.G171A, p.T187K, p.R212K, p.T269M, p.R373W, p.I440N, p.R461Q,
      p.N533Y, p.C644F, p.H651R, p.V705M, p.N732K, p.G771R, p.H775R, p.T830M, p.A841P,
      p.D880V, p.S957P and p.R966G). Mutation analysis allowed us to identify sequence
      alterations in both alleles for 19 patients and in one allele for 7 patients One
      patient was carrying three mutations (p.Y138F, p.T269M and p.E153X) and one
      patient was carrying two amino acid substitutions on the same allele (p.V705M and
      p.R212K) and an unidentified mutation on the other allele. No mutation could be
      found in two patients, suggesting possible defects in the H-protein or gene
      alterations that could not be identified by our technique. The potential use of
      genotype determination for prenatal diagnosis is emphasized.

PMID- 16601881
TI  - Expression profiling reveals multiple myelin alterations in murine succinate
      semialdehyde dehydrogenase deficiency.
AB  - Succinic semialdehyde dehydrogenase (SSADH) deficiency, a rare genetic defect of
      GABA degradation recently modelled in mice (SSADH(-/-) mice), manifests early
      absence seizures that evolve into generalized convulsive seizures and lethal
      status epilepticus in gene-ablated mice. Disrupted GABA homeostasis, in
      conjunction with the epileptic phenotype and increased gamma-hydroxybutyric acid
      (GHB), suggested that expression profiling with the U74Av2 Affymetrix system
      would reveal dysregulation of receptor genes associated with GABAergic and
      glutamatergic neurotransmission. Unexpectedly, we found significant
      downregulation for genes associated with myelin biogenesis and compaction,
      predominantly in hippocampus and cortex. These results were confirmed by: (1)
      myelin basic protein (MBP) immunohistochemistry; (2) western blotting of myelin
      associated glycoprotein (MAG) and MBP; (3) qRT-PCR analyses of myelin-associated
      oligodendrocytic basic protein (MOBP), MAG, MBP and proteolipid protein (PLP) in
      hippocampus, cortex and spinal cord; (4) quantitation of ethanolamine and choline
      plasmalogens, all core myelin components; (5) evaluation of myelin content in
      brain sections employing toluidine blue staining; and (6) ultrastructural
      evaluation of myelin sheath thickness via electron microscopy. We speculate that
      increased GABA/GHB, acting through GABAergic systems, results in decreased levels
      of the neurosteroids progesterone and allopregnanolone [Gupta et al (2003) Ann
      Neurol 54(Supplement 6): S81-S90] and phosphorylation of mitogen-activated
      protein (MAP) kinase, with resulting myelin protein abnormalities primarily in
      the cortex of SSADH(-/-) mice.

PMID- 16601882
TI  - Biochemical compared to molecular diagnosis in acute intermittent porphyria.
AB  - The biochemical and the molecular diagnoses of an inherited porphyria require
      experience. False positive or negative screening tests and the low penetrance of
      the disease make a correct diagnosis difficult.The biochemical and the molecular
      procedures for the diagnosis of acute intermittent porphyria were applied to five
      unrelated patients suffering from acute intermittent porphyria. All patients were
      shown to be gene carriers of acute intermittent porphyria by both methods. The
      two different possibilities of the diagnosis corresponded well. In a family
      definitively identified by molecular diagnosis of one of the patients and his
      relatives, the patient's two children were asymptomatic. His son was shown to be
      a gene carrier of the father's deficiency by biochemical as well as molecular
      analysis, whereas his daughter was not affected by acute intermittent porphyria.

PMID- 16601883
TI  - Diagnosis and management of trimethylaminuria (FMO3 deficiency) in children.
AB  - Persistent trimethylaminuria in children is caused by autosomal recessively
      inherited impairment of hepatic trimethylamine (TMA) oxidation due to deficiency
      of flavin monooxygenase 3 (FMO3) secondary to mutations in the FMO3 gene.
      Trimethylaminuria or 'fish odour syndrome' is due to excessive excretion into
      body fluids and breath of TMA derived from the enterobacterial metabolism of
      dietary precursors. The disorder is present from birth but becomes apparent as
      foods containing high amounts of choline or of trimethylamine N-oxide (TMAO) from
      marine (sea or saltwater) fish are introduced into the diet. In our experience,
      trimethylaminuria (FMO3 deficiency) in children is rare. We have compared the
      dynamics and diagnostic efficacy of choline loading with marine fish meals in six
      children with trimethylaminuria. Loading with a marine fish meal provides a
      simple and acceptable method for confirmation of diagnosis of suspected
      trimethylaminuria in children, with the effects being cleared more quickly than
      with a choline load test. However, oral loading with choline bitartrate allows
      estimation of residual oxidative capacity in vivo and is a useful adjunct to
      molecular studies. Patients homozygous for the 'common' P153L mutation in the
      FMO3 gene showed virtual complete lack of residual TMA N-oxidative capacity,
      consistent with a nonfunctional or absent FMO3 enzyme, whereas a patient with the
      M82T mutation showed some residual oxidative capacity. A patient compound
      heterozygous for two novel mutations, G193E and R483T, showed considerable
      residual N-oxidative capacity. A further patient, heterozygous for two novel
      sequence variations in the FMO3 gene, consistently showed malodour and elevated
      urinary TMA/TMAO ratios under basal conditions but a negative response to both
      choline and marine fish meal loading. Comparison of the effects of administration
      of antibiotics (metronidazole, amoxicillin, neomycin) on gut bacterial production
      of trimethylamine from choline showed they all reduced TMA production to a
      limited extent, with neomycin being most effective. 'Best-practice' diagnostic
      and treatment guidelines are summarized.

PMID- 16601884
TI  - Acrodermatitis acidaemia secondary to 'overtreatment' and protein deficiency.

PMID- 16601885
TI  - A study on the nature of genetic metabolic practice at a major paediatric
      referral centre.
AB  - A retrospective chart review of new paediatric patients seen during the calendar
      year 1998 by specialists of the Division of Clinical and Metabolic Genetics of
      the Hospital for Sick Children in Toronto, the largest such referral centre in
      the country, showed that 81% of specific genetic metabolic diagnoses were made
      within one month of being seen in consultation by one of the consultants of the
      programme. In 5% of cases, a specific diagnosis was not reached 4 years after
      initial consultation. We concluded from this study that the specific diagnosis of
      inborn errors of metabolism at a major medical genetic referral centre tended to
      be made quickly, or never. Some of the causes of delays in diagnosis include (1)
      the lack of ready access to existing diagnostic laboratory testing; (2) technical
      barriers to the identification of specific metabolic or genetic defects; and (3)
      incomplete knowledge of genetic defects causing inherited metabolic diseases.

PMID- 16601886
TI  - An unusual clinical and biochemical presentation of ornithine transcarbamylase
      deficiency in a male patient.
AB  - We report a male patient with a history of recurrent idiopathic vomiting, normal
      plasma ammonia and glutamine concentrations in acute phase, who died at 3 years
      of age. Ornithine transcarbamylase deficiency was diagnosed after detecting
      elevated urinary orotate concentrations in a sample collected just before death,
      and the diagnosis was confirmed by DNA analysis.

PMID- 16601887
TI  - Two cases of citrullinaemia presenting with stroke.
AB  - Urea cycle disorders are known to be unusual causes of stroke. We report two
      infant cases of citrullinaemia that both initially presented with a stroke and
      suggest that urea cycle disorders should be included in the differential
      diagnosis of unexplained stroke during infancy and childhood.

PMID- 16601888
TI  - Successful liver transplantation for argininosuccinate lyase deficiency (ASLD).
AB  - Liver transplantation was performed in a girl with early-onset ASLD, leading to
      unrestricted protein intake and no further neurological deterioration.

PMID- 16601889
TI  - HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with
      fulminant hepatitis-like presentation.
AB  - We report a 3-year-old Italian patient with the hyperornithinaemia,
      hyperammonaemia, homocitrullinuria (HHH) syndrome who presented with neurological
      deterioration after an intercurrent infection. Hyperammonaemia, coagulopathy and
      moderate hypertransaminasaemia were detected on hospital admission. Severe
      hepatocellular necrosis with hypertransaminasaemia (aspartate aminotransferase
      20,000 UI/L, alanine aminotransferase 18,400 UI/L) and coagulopathy (PT < 5%)
      rapidly developed within few days, prompting evaluation for liver
      transplantation. A protein-restricted diet and arginine supplementation were
      immediately started, with a rapid improvement of the patient's neurological
      conditions and normalization of liver function tests and blood ammonia. The
      diagnosis of HHH syndrome was based on the presence of the typical metabolic
      abnormalities. Molecular analysis of the SLC25A15 gene showed that the patient
      was heterozygous for two novel mutations (G113C and M273K). The diagnosis of HHH
      syndrome should be considered in patients with fulminant hepatitis-like
      presentations. Early identification and treatment of these patients can be life
      saving and can avoid liver transplantation.

PMID- 16601890
TI  - The longest-surviving patient with classical maple syrup urine disease.
AB  - The clinical problems, dietary management and biochemical monitoring over a 40
      year period of the longest-surviving patient with maple syrup urine disease are
      described. Her case illustrates that a good outcome can be obtained with early
      diagnosis and institution of a diet restricted in branched-chain amino acids.
      Changes in dietary supplementation have benefited her in terms of nutrition and
      quality of life. Consistently high blood concentrations of branched-chain amino
      acids have not been associated with neuropsychometric decline.

PMID- 16601891
TI  - Atypical phenotype in a boy with a maple syrup urine disease.
AB  - Maple syrup urine disease (MSUD) is a metabolic disorder due to a block in the
      decarboxylation step in the catabolic pathways of the branched-chain amino acids
      (BCAAs). We describe an atypical presentation in an infant male. The patient
      presented with psychomotor retardation, profound hypotonia and elevated plasma
      levels of BCAAs, but no elevation of alloisoleucine. Cranial magnetic resonance
      imaging showed prominent diffuse CSF spaces, delayed myelin maturation and
      symmetrical signal abnormality within the globi pallidi, midbrain, dorsal pons
      and medulla. The cerebellar white matter was specifically spared. A mitochondrial
      disorder was suggested. After correction of feeding problems with G-tube feeds,
      his high BCAAs persisted and, on fourth analysis, alloisoleucine was seen.
      Subsequent fibroblast enzyme and mutation analysis confirmed MSUD due to E(1)
      alpha subunit deficiency. After starting dietary treatment, there was no
      significant improvement in his hypotonia or his psychomotor development. However,
      the high signal within the globi pallidi had resolved. MSUD may have diverse
      clinical presentations, and should be considered in children who present with
      chronic psychomotor delay but no acute encephalopathic episodes. BCAA levels may
      not be very high, alloisoleucine may not always be detected in MSUD even with
      severe enzyme deficiency, and imaging may be misleading if seen in the chronic
      phase only.

PMID- 16601892
TI  - Neuropsychometric outcome predictors for adults with maple syrup urine disease.
AB  - We describe 14 adult MSUD patients (3 with intermediate MSUD) with varied
      clinical and neuropsychometric outcomes. Age at diagnosis appears to be a
      predictor of IQ even in adults, while long-term blood leucine does not correlate
      with IQ.

PMID- 16601893
TI  - Biochemical and molecular diagnosis of lipoamide dehydrogenase deficiency in a
      North American Ashkenazi Jewish family.
AB  - A late-onset presentation of lipoamide dehydrogenase (E3) deficiency is described
      in a North American Ashkenazi Jewish (AJ) family. Diagnosis was made by urine
      organic acid and molecular analyses.

PMID- 16601894
TI  - Isolated 3-methylcrotonyl-coenzyme A carboxylase deficiency in a child with
      metabolic stroke.
AB  - We report a 3-year-old boy with isolated 3-methylcrotonyl-coenzyme A deficiency
      with unexpectedly severe presentation, seizures and history of cerebral ischae
      mic episode.

PMID- 16601895
TI  - Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency.
AB  - Mitochondrial HMG-CoA synthase deficiency is an inherited metabolic disorder
      caused by a defect in the enzyme that regulates the formation of ketone bodies.
      Patients present with hypoketotic hypoglycaemia, encephalopathy and hepatomegaly,
      usually precipitated by an intercurrent infection or prolonged fasting. The
      diagnosis may easily be missed as previously reported results of routine
      metabolic investigations, urinary organic acids and plasma acylcarnitines may be
      nonspecific or normal, and a high index of suspicion is required to proceed to
      further confirmatory tests. We describe a further acute case in which the
      combination of urinary organic acids, low free carnitine and changes in the
      plasma acylcarnitine profile on carnitine supplementation were very suggestive of
      a defect in ketone synthesis. The diagnosis of mitochondrial HMG-CoA synthase
      deficiency was confirmed on genotyping, revealing two novel mutations: c.614G > A
      (R188H) and c.971T > C (M307T). A further sibling, in whom the diagnosis had not
      been made acutely, was also found to be affected. The possible effects of these
      mutations on enzyme activity are discussed.

PMID- 16601896
TI  - The first patient diagnosed with cytochrome c oxidase deficient Leigh syndrome:
      progress report.
AB  - Mutations in SURF1, an assembly gene for cytochrome c oxidase (COX), the fourth
      complex of the oxidative phosphorylation system, are most frequently encountered
      in patients with COX deficiency. We describe a patient with Leigh syndrome
      harbouring a mutation in SURF1 who was reported decades ago with a tissue
      specific cytochrome c oxidase deficiency.

PMID- 16601897
TI  - X-linked creatine transporter defect: a report on two unrelated boys with a
      severe clinical phenotype.
AB  - We report two unrelated boys with the X-linked creatine transporter defect (CRTR)
      and clinical features more severe than those previously described with this
      disorder. These two boys presented at ages 12 and 30 months with severe mental
      retardation, absent speech development, hypotonia, myopathy and extra-pyramidal
      movement disorder. One boy has seizures and some dysmorphic features; he also has
      evidence of an oxidative phosphorylation defect. They both had classical absence
      of creatine peak on brain magnetic resonance spectroscopy (MRS). In one, however,
      this critical finding was overlooked in the initial interpretation and was
      discovered upon subsequent review of the MRS. Molecular studies showed large
      genomic deletions of a large part of the 3' end of the complete open reading
      frame of the SLC6A8 gene. This report emphasizes the importance of MRS in
      evaluating neurological symptoms, broadens the phenotypic spectrum of CRTR and
      adds knowledge about the pathogenesis of creatine depletion in the brain and
      retina.

PMID- 16601898
TI  - X-Linked creatine transporter deficiency in two patients with severe mental
      retardation and autism.
AB  - We describe the first two unrelated Spanish patients with creatine transporter
      deficiency initially identified by brain proton magnetic resonance spectroscopy
      (MRS). The clinical phenotype was characterized by severe mental retardation,
      epilepsy, autism, severe speech delay and absence of brain creatine by MRS. Urine
      creatine/creatinine ratio was increased and creatine uptake in fibroblasts was
      impaired in both patients. On DNA sequence analysis of the SLC6A8/creatine
      transporter gene, one hemizygous mutation was found in each patient: one mutation
      was novel and consisted of a deletion of two nucleotides c.878-879delTC in exon
      5, resulting in a frameshift (p.Lys293fsX3), and in the other patient a known
      deletion of three nucleotides 1222-1224delTTC in exon 8 resulting in p.Phe408del.
      Creatine treatment for one year failed to improve the neurological symptoms and
      was associated with a striking increase in body weight in both patients (13 and
      16 kg, respectively).

PMID- 16601899
TI  - A patient with common glycogen storage disease type Ib mutations without
      neutropenia or neutrophil dysfunction.
AB  - We describe a 16-year old boy with glycogen storage disease type Ib, homozygous
      for the common 1211-1212delCT mutation, who never experienced neutropenia, and
      did not suffer from frequent infections or inflammatory bowel disease. In
      addition, neutrophil function tests showed no abnormalities.

PMID- 16601900
TI  - The effect of L-alanine therapy in a patient with adult onset glycogen storage
      disease type II.
AB  - Adult-onset glycogen storage disease type II (GSD II) (McKusick 232300) is a
      progressive disabling myopathy. At present there is no treatment of proven
      clinical efficacy. Enzyme replacement therapy may in the future provide benefit
      but it will be costly and is not yet freely available. L-Alanine, a simple and
      relatively cheap therapy, has been shown to reduce protein degradation in GSD II
      patients but has not previously been assessed for clinical benefit in a
      controlled study. In this study L-alanine was assessed in a double blind, placebo
      controlled, crossover n = 1 study. Assessments consisted of spirometry,
      cardiopulmonary exercise testing, quality of life measurements, biochemical
      markers and assessment by the criterion 4-component model of body composition.
      Alanine therapy was associated with a 15% gain in total body protein. However,
      the patient showed no functional improvement and reported feeling worse after
      treatment. Further controlled studies in a small group may be warranted, but not
      widespread use of this therapy.

PMID- 16601901
TI  - Effect of discontinuing of laronidase in a patient with mucopolysaccharidosis
      type I.
AB  - We present a patient on enzyme replacement therapy who showed rapid deterioration
      when laronidase was discontinued owing to pregnancy.

PMID- 16601902
TI  - Acid sphingomyelinase deficiency: cardiac dysfunction and characteristic findings
      of the coronary arteries.
AB  - Two sisters with type B Niemann-Pick disease (genotype: S436R/S436R) showed
      cardiac dysfunctions, not secondary to pulmonary disease, at the beginning of the
      third decade. In the younger sister, myocardial dysfunction was refractory to
      treatment, resulting in death. At autopsy, the distal branches of the coronary
      arteries showed narrowing of the arterial lumina due to swelling of the medial
      and intimal smooth-muscle cells. This is the first report describing
      characteristic findings of coronary arteries in type B Niemann-Pick disease.

PMID- 16601903
TI  - Stabilization of hypoglycosylation in a patient with congenital disorder of
      glycosylation type Ia.
AB  - A follow-up over 7 years on a patient with congenital disorder of glycosylation
      type Ia showed a significant normalization of hypoglycosylated transferrin.
      Isoelectric focusing for serum transferrin is a widely used screening method but
      there could be a limit of detection and the subtle changes can be also
      overlooked. Re-test with a different method is desirable, especially when the
      clinical suspicion for congenital disorder of glycosylation is high.

PMID- 16601904
TI  - Severe normotensive metabolic alkalosis in a 2-month-old boy with hyperekplexia.
AB  - A 2-month-old infant with hereditary hyperekplexia, umbilical and bilateral
      inguinal hernias and history of poor feeding was noted to have severe
      normotensive metabolic alkalosis: sodium 132 mmol/L, potassium 3.4 mmol/L,
      chloride 77 mmol/L, pH 7.55, carbon dioxide tension 56.3 mmHg and bicarbonate
      48.0 mmol/L. After parenteral rehydration and treatment with clonazepam,
      laboratory parameters normalized.

PMID- 16601905
TI  - Dietary compliance in ornithine aminotransferase deficiency.
AB  - Ornithine delta-aminotransferase (OAT) deficiency (McKusick 258870) is associated
      with hyperornithinaemia, thought to be the cause of the progressive retinal
      degeneration that occurs in this disorder. For the large majority of cases
      unresponsive to the co-factor pyridoxine, treatment is based on reducing
      ornithine plasma levels below 400 micromol/L with an arginine-restricted diet.
      This has been shown to slow the progression of retinal disease. (Santinelli et al
      2004). In Table 1 we present our experience in the dietary management of 12
      patients (7 female) from 8 families. Compliance was defined as good, intermediate
      or poor according to plasma ornithine levels. Only one patient could be
      categorized as a good complier, 5 were intermediate, and 6 were poor. The age at
      start of treatment was the most important factor as regards ability to comply
      with diet. Our study emphasizes the difficulty with dietary treatment and need
      for early diagnosis. For the older patients, alternative treatments such as the
      use of oral lysine to increase renal losses of ornithine need to be investigated
      further (Peltola et al 2000).

PMID- 16601906
TI  - Calculation of the reliability of the allopurinol load in detecting carriers for
      ornithine transcarbamylase deficiency.

PMID- 16601912
TI  - A novel IL2RG mutation associated with maternal T lymphocyte engraftment in a
      patient with severe combined immunodeficiency.
AB  - Severe combined immunodeficiency (SCID) represents a genetically heterogeneous
      group of primary immunodeficiency disorders. Irrespective of the genetic defect,
      patients with SCID may be engrafted with transplacentally derived maternal T
      lymphocytes that in a subset of cases may be responsive to phytohemagglutinin.
      Here, we present, from a genetic perspective, an SCID patient who not only
      harbored a novel mutation in the gene encoding the common gamma chain (gamma c)
      of the IL-2 receptor (IL2RG), but also carried reactive maternal T lymphocytes
      that produced a karyotype that was initially perplexing.

PMID- 16601913
TI  - Phenol degradation by immobilized cold-adapted yeast strains of Cryptococcus
      terreus and Rhodotorula creatinivora.
AB  - Three strains were isolated from hydrocarbon-polluted alpine habitats and were
      representatives of Cryptococcus terreus (strain PB4) and Rhodotorula creatinivora
      (strains PB7, PB12). All three strains synthesized and accumulated glycogen (both
      acid- and alkali-soluble) and trehalose during growth in complex medium
      containing glucose as carbon source and in minimal salt medium (MSM) with phenol
      as sole carbon and energy source. C. terreus strain PB4 showed a lower total
      accumulation level of storage compounds and a lower extracellular polysaccharides
      (EPS) production than the two R. creatinivora strains, PB7 and PB12. Biofilm
      formation and phenol degradation by yeast strains attached to solid carriers of
      zeolite or filter sand were studied at 10 degrees C. Phenol degradation by
      immobilized yeast strains was always higher on zeolite compared with filter sand
      under normal osmotic growth conditions. The transfer of cells immobilized on both
      solid supports to a high osmotic environment decreased phenol degradation
      activity by all strains. However, both R. creatinivora PB7 and PB12 strains
      maintained higher ability to degrade phenol compared with C. terreus strain PB4,
      which almost completely lost its phenol degradation activity. Moreover, R.
      creatinivora strain PB7 showed the highest ability to form biofilm on both
      carriers under high osmotic conditions of cultivation.

PMID- 16601914
TI  - Molecular identification of a novel beta-1,3-glucanase from alkaliphilic
      Nocardiopsis sp. strain F96.
AB  - Alkaliphilic Nocardiopsis sp. strain F96 produced three beta-1,3-glucanase
      isozymes of different molecular masses (BglF1, BglF2 and BglF3). The N-terminal
      amino acid sequences of BglFs indicated that these isozymes were the products of
      a single gene. The beta-1,3-glucanase gene (bglF) was cloned from the chromosomal
      DNA of strain F96. The bglF gene encoded a polypeptide of 270 amino acids
      including a signal sequence. The deduced amino acid sequence of mature BglF
      exhibited the highest homology to those of glycoside hydrolase (GH) family 16
      beta-1,3-glucanases, suggesting that the enzyme belonged to the GH family 16. The
      mature region of bglF gene was functionally expressed in Escherichia coli. The
      optimum pH and temperature of purified recombinant BglF were pH 9.0 and 70
      degrees C, respectively. This enzyme efficiently hydrolyzed insoluble beta-1,3
      glucans and showed the highest activity toward a beta-1,3-1,4-glucan rather than
      beta-1,3-glucans. These results suggested that BglF would be a novel beta-1,3
      glucanse. Mutational analysis revealed that Glu123 and Glu128 should be the
      catalytic residues of BglF.

PMID- 16601916
TI  - Is SAPHO syndrome a target for antibiotic therapy?
AB  - The etiology of the synovitis, acne, pustulosis, hyperostosis, and osteitis
      (SAPHO) syndrome remains unclear. Infectious factors are proposed to be relevant
      in the etiopathogenesis of the disease. To our knowledge, this is the first
      reported case of a proposed relationship between Staphylococcus aureus cultured
      from plantar pustule and SAPHO syndrome, which was successfully treated with co
      trimoxazole (CTM) (sulfamethoxazole/trimetoprim). CTM might be the drug of choice
      for therapy for SAPHO syndrome because of combined antibiotic and
      immunomodulatory properties. Hypersensitivity testing of the medication in vitro
      was performed to identify, in the preclinical stage, the hypersensitivity
      reaction to CTM, which may have been severe.

PMID- 16601915
TI  - High frequency of maternal vitamin B12 deficiency as an important cause of
      infantile vitamin B12 deficiency in Sanliurfa province of Turkey.
AB  - BACKGROUND: Vitamin B12 deficiency in infancy may cause failure to thrive, severe
      neurological disorders and megaloblastic pancytopenia. It is well known that
      infants born with deficient vitamin B12 storage have increased the risk of
      vitamin B12 deficiency. Vitamin B12 deficiency is more prevalent in infancy in
      Sanliurfa province (at the southeast region of Turkey). AIM OF THE STUDY: The aim
      of this study was to determine the frequencies of vitamin B12, folic acid and
      iron deficiencies in pregnants and their babies at birth and to what extend the
      mothers' deficiency becomes effective on babies' deficiencies. METHODS: The study
      groups were constituted by 180 pregnant women and their single and term babies.
      Venous blood samples of pregnants were obtained 1-3 h before delivery and babies'
      cord bloods were collected at birth. Vitamin B12 and folic acid levels were
      measured with electro chemiluminiscence method; serum iron and iron binding
      capacities were measured by colorimetric method and complete blood counts were
      performed by automatic blood counter. RESULTS: Mean vitamin B12 levels in
      maternal and cord blood serum were 130 +/- 61.7 pg/ml and 207 +/- 141 pg/ml; mean
      folic acid levels were 8.91 +/- 6.46 ng/ml and 17.8 +/- 11.8 ng/ml; mean serum
      iron levels were 56.9 +/- 37.5 microg/dl and 147 +/- 43.2 microg/dl; and mean
      transferrin saturations were 11.8 +/- 8% and 65.6 +/- 24%, respectively. There
      were vitamin B12 deficiency (<160 pg/ml) in 72% of the mothers and 41% of the
      babies, and severe deficiency (<120 pg/ml) in 48% of the mothers and 23% of the
      babies. Folic acid deficiency was found in 12% of the mothers, but was not found
      in the babies. There were iron deficiency in 62% of the mothers and 1% of the
      babies. There were statistically significant correlation between maternal and
      cord blood serum vitamin B12 levels (r = 0.395, P < 0.001) and folic acid levels
      (r = 0.227, P = 0.017), while there were no correlation between maternal and cord
      blood iron levels and transferrin saturations. CONCLUSION: The study results
      showed that vitamin B12 deficiency is prevalent in pregnants in this region and
      that 41% of infants have born with deficient vitamin B12 storages. Therefore,
      prophylactic use of vitamin B12 by pregnant women in Sanliurfa and other poor
      communities could have considerable benefits to prevent vitamin B12 deficiency
      and its complications in infants.

PMID- 16601917
TI  - Tabetic arthropathy. A report of 43 cases.
AB  - Destructive tabetic arthropathy (TA) has become rare in the course of syphilis
      because of early diagnosis and treatment. TA is difficult to manage because of
      the severity of the handicap and the absence of a specific treatment. We describe
      the clinical, biological, and radiological characteristics of TA. In this paper,
      we performed a retrospective study of 24 patients with TA from 1983 to 2003.
      Inclusion criteria were typical radiological findings and positive syphilitic
      serology in blood and/or synovial fluid and/or cerebrospinal fluid. Included in
      the study were 15 men and 9 women, their mean age was 53.71+/-12.25 years, and
      the delay of diagnosis was 36.83+/-53.03 months. Thirteen patients (54.2%) had a
      known primary syphilitis. In the studied cases, 43 of the patients' joints were
      involved, which concerned knees, hips, the spine, and ankles in 91.66, 8.33,
      8.33, and 4.16% of cases, respectively. TA was bilateral in 62.5% and multifocal
      in 8.3%. The neurological exam found signs suggesting tabes dorsalis in seven
      cases. The osteoarticular exam showed an abnormal range of mobility (n=25),
      hydarthrosis, and articular deformation (n=17). Syphilitic serology tests were
      positive in synovial fluid, cerebrospinal fluid, and blood in 12 (50%), 8
      (33.33%), and 24 (100%) cases, respectively. Radiological exam showed atrophic
      and hypertrophic forms. The frequency and severity of TA in our study may be
      explained by the frequency of atypical forms of syphilitis and the absence of
      penicillin in Morocco in the 1950s.

PMID- 16601919
TI  - Negative correlation between bone mineral density and TSH receptor antibodies in
      male patients with untreated Graves' disease.
AB  - INTRODUCTION: Although it has been established that hyperthyroidism leads to
      reduced bone mineral density (BMD), with accelerated bone turnover promoting bone
      resorption in female patients, there is a dearth of data for male patients with
      hyperthyroidism. This study evaluated BMD and bone metabolism in male patients
      with Graves' disease. METHODS: The study included 56 Japanese male patients with
      newly diagnosed Graves' disease and 34 normal Japanese male control subjects of
      similar age and body mass index. We used dual energy x-ray absorptiometry to
      measure BMD at sites with different cortical/cancellous bone ratios (lumbar
      spine, femoral neck, and distal radius). RESULTS: At the lumbar spine and the
      distal radius, BMD and T-scores were significantly lower for patients than for
      controls. At the femoral neck, on the other hand, the same values were
      relatively, but not significantly, lower in patients than in controls. However, Z
      scores at all three sites were significantly lower for patients than for
      controls. The Z -score at the distal radius of patients was significantly lower
      than that at their lumbar spine and femoral neck. In addition, Z-score at the
      distal radius correlated negatively with age, free thyroxine, thyroid stimulating
      hormone receptor antibodies, thyroid stimulating antibody, and urinary N-terminal
      telopeptide of type I collagen normalized by creatinine. CONCLUSIONS: These
      results indicate a high prevalence of cortical bone loss in male patients with
      Graves' disease, especially elderly patients. We conclude that BMD measurement is
      crucial in all Graves' disease patients regardless of their gender and that the
      radial BMD as well as BMD at the lumbar spine and femoral neck should be
      monitored to effectively prevent bone loss and subsequent fracture.

PMID- 16601918
TI  - Women with hip fracture have a greater rate of decline in bone mineral density
      than expected: another significant consequence of a common geriatric problem.
AB  - INTRODUCTION: Hip fracture is a major public health problem, annually affecting
      over 350,000 persons in the United States and 1.6 million worldwide. Consequences
      include decreased survival, loss of independence, and increased risk of
      subsequent fractures. A substantial decline in bone mineral density (BMD) also
      occurs, yet the magnitude of the decline specifically attributable to hip
      fracture has not been documented. METHODS: To determine the amount of BMD decline
      attributable to hip fracture, the rate of decline in BMD in a cohort of hip
      fracture patients was compared with that in a cohort of women of similar age and
      BMD but without hip fracture. All subjects were community dwelling when enrolled.
      Hip fracture patients in the Baltimore Hip Studies (BHS) came from two hospitals
      in Baltimore, Maryland, from 1992 through 1995; comparison subjects came from the
      Study of Osteoporotic Fracture (SOF) enrolled in four areas of the United States
      during the same period. Eighty-four white, female hip fracture patients 65 years
      and older from the BHS were compared with 168 SOF participants matched on age,
      race, and BMD at baseline. BMD of the femoral neck and total hip was measured by
      dual-energy x-ray absorptiometry. RESULTS: Hip fracture patients had a greater
      decline in BMD during the 12-month postfracture follow-up than that expected on
      the basis of the nonfracture cohort: 4.9% vs. 0.4% at the femoral neck and 3.5%
      vs. 0.7% for the total hip. The decline in BMD in hip fracture patients was 11.8
      times the amount expected at the femoral neck (matched on age and baseline BMD
      and adjusted for between-cohort differences in smoking prevalence) and 4.9 times
      that expected for the total hip at the end of 1 year after the hip fracture.
      CONCLUSION: In this sample of older women, bone loss over the year following hip
      fracture far exceeded that expected and is an important clinical management
      concern.

PMID- 16601920
TI  - Reduction of dietary magnesium by only 50% in the rat disrupts bone and mineral
      metabolism.
AB  - INTRODUCTION: The objective of this study was to determine the effect of a
      moderate reduction of dietary magnesium [50% of nutrient requirement (50% NR)] on
      bone and mineral metabolism in the rat, and to explore possible mechanisms for
      the resultant reduced bone mass. METHODS: Female rats were 6 weeks of age at the
      start of study. Serum magnesium (Mg), calcium (Ca), parathyroid hormone (PTH),
      1,25(OH)(2)-vitamin D, alkaline phosphatase, osteocalcin, and pyridinoline were
      measured during the study at 3- and 6-month time points in control (dietary Mg of
      100% NR) and Mg-deficient animals (dietary Mg at 50% NR). Femurs and tibias were
      also collected for mineral content analyses, micro-computerized tomography,
      histomorphometry, and immunohistochemical localization of substance P, TNFalpha,
      and IL-1beta at 3 and 6 months. RESULTS: Although no significant change in serum
      Mg was observed, Mg deficiency developed, as assessed by the reduction in bone Mg
      content at the 3- and 6-month time points (0.69+/-0.05 and 0.62+/-0.04% ash,
      respectively, in the Mg depletion group compared to 0.74+/-0.04 and 0.67+/-0.04%
      ash, respectively, in the control group; p=0.0009). Hypercalcemia did not
      develop. Although serum Ca level remained in the normal range, it fell
      significantly with Mg depletion at 3 and 6 months (10.4+/-0.3 and 9.6+/-0.3
      mg/dl, respectively, compared to 10.5+/-0.4 and 10.1+/-0.6 mg/dl, respectively,
      in the control group; p=0.0076). The fall in serum Ca in the Mg-depleted animals
      was associated with a fall in serum PTH concentration between 3 and 6 months
      (603+/-286 and 505+/-302 pg/ml, respectively, although it was still higher than
      the control). The serum 1,25(OH)(2)-vitamin D level was significantly lower in
      the Mg depletion group at 6 months (10.6+/-7.1 pg/ml) than in the control (23.5+/
      12.7 pg/ml) (p<0.01 by the t-test). In Mg-deficient animals, no difference was
      noted in markers of bone turnover. Trabecular bone mineral content gain was less
      over time in the distal femur with Mg deficiency at 3 and 6 months (0.028+/-0.005
      and 0.038+/-0.007 g, respectively, compared to 0.027+/-0.004 and 0.048+/-0.006 g,
      respectively, in the control group; p<0.005). Histomorphometry at these time
      points demonstrated decreased trabecular bone volume (15.76+/-1.93 and 14.19+/
      1.85%, respectively, compared to 19.24+/-3.10 and 17.30+/-2.59%, respectively, in
      the control group; p=0.001). Osteoclast number was also significantly increased
      with Mg depletion (9.07+/-1.21 and 13.84+/-2.06, respectively, compared to 7.02+/
      1.89 and 10.47+/-1.33, respectively, in the control group; p=0.0003). Relative to
      the control, immunohistochemical staining intensity of the neurotransmitter
      substance P and of the cytokines TNFalpha and IL-1beta was increased in cells of
      the bone microenvironment in the Mg depletion group, suggesting that inflammatory
      cytokines may contribute to bone loss. CONCLUSION: These data demonstrate that Mg
      intake of 50% NR in the rat causes a reduced bone mineral content and reduced
      volume of the distal femur. These changes may be related to altered PTH and
      1,25(OH)(2)-vitamin D formation or action as well as to an increase release of
      substance P and the inflammatory cytokines TNFalpha and IL-1beta.

PMID- 16601921
TI  - Cardioprotective effect of lycopene in the experimental model of myocardial
      ischemia-reperfusion injury.
AB  - The efficacy of lycopene to limit myocardial injury after ischemia and
      reperfusion was explored in the present study. Adult male albino Wistar rats were
      divided into three experimental groups and orally received olive oil as vehicle
      (sham and control I-R) or lycopene 1 mg/kg dissolved in olive oil (lycopene
      treated group) respectively for 31 days. On the 31st day, animals of the control
      I-R and lycopene treated groups were subjected to 45 min of occlusion of the LAD
      coronary artery and were thereafter reperfused for 1 h. The ischemia-reperfusion
      injury resulted in significant cardiac necrosis, depression in hemodynamics,
      decline in antioxidant status and rise in lipid peroxidation product levels in
      the control I-R group as compared to sham control. In histopathological
      examinations myocardial damage produced after I-R was significantly prevented in
      the lycopene treated group. Lycopene treatment resulted in preservation of the
      myocardial antioxidant status and altered hemodynamic parameters as compared to
      control I-R group. Furthermore, I-R-induced lipid peroxidation was significantly
      inhibited in the lycopene treated group. These beneficial cardioprotective
      effects also translated into the functional recovery of the heart. The beneficial
      effect of lycopene likely results from the suppression of oxidative stress, which
      results in the reduction of myocardial injury.

PMID- 16601922
TI  - Identification of large-scale molecular changes of Autotaxin(ENPP2) knock-down by
      small interfering RNA in breast cancer cells.
AB  - To understand comprehensive molecular mechanisms by which Autotaxin (ENPP2)
      mediates, we identified large-scale molecular changes responsible for aberrant
      expression of Autotaxin (ATX) on breast cancer cells by using DNA microarrays.
      Transcriptional over-expression of ENPP2 gene was endogenously silenced by using
      RNA interference technique, and then recapitulated corresponding molecular
      changes in MDA435 breast cancer cells. Application of nonparametric Wilcoxon
      statistical analyses (P<0.05) and the selection criteria of 2-fold differential
      gene expression change resulted in the identification of 368 genes including 133
      up-regulated and 235 genes under-expressed in ENPP2-silencing MDA435 cells. Most
      of the functional categories of identified genes are associated with cellular
      metabolism, cytoskeleton organization, transcription regulation, signal
      transduction as well as cellular organization and biogenesis. Our data suggest
      that the molecular signature identified by the ENPP2-silencing methods may
      represent potential candidates that can explain the complicated characteristics
      of ATX and may serve as biomarkers, for the development of molecular-targeting
      therapy, in human breast cancer.

PMID- 16601923
TI  - Discovery of the molecular machinery CERT for endoplasmic reticulum-to-Golgi
      trafficking of ceramide.
AB  - Synthesis and sorting of lipids are essential events for membrane biogenesis and
      its homeostasis. Ceramide is synthesised at the endoplasmic reticulum (ER), and
      translocated to the Golgi compartment for conversion to sphingomyelin (SM). We
      have recently identified a key factor (named CERT) for ceramide trafficking. In
      this short review, I summarise recent advances in molecular mechanisms of
      intracellular transport of ceramide, focusing on our genetic and biochemical
      approaches to this issue.

PMID- 16601924
TI  - Biological and sequence data suggest that potato rough dwarf virus (PRDV) and
      potato virus P (PVP) are strains of the same species.

PMID- 16601925
TI  - The complete nucleotide sequence of a capsicum chlorosis virus isolate from
      Lycopersicum esculentum in Thailand.
AB  - The complete nucleotide sequence of a tospovirus isolated from Lycopersicum
      esculentum in Thailand was determined. The L RNA comprises of 8912 nt and codes
      for the RNA-dependent RNA-polymerase (RdRp) (2877 aa). Two ORFs are located on
      the M RNA (4823 nt) encoding the non-structural (NSm) protein (308 aa) and the
      viral glycoprotein precursors (Gn/Gc) (1121 aa) separated by an intergenic region
      of 433 nt. ORFs coding for the non-structural (NSs) and nucleocapsid (N) protein,
      439 aa and 275 aa, respectively, were identified on the S RNA (3477 nt) separated
      by an intergenic region of 1202 nt. The N protein of the Thailand isolate was
      most closely related to that of capsicum chlorosis virus (CaCV), sharing an amino
      acid sequence identity of 92.7%. Additionally, multiple sequence analyses
      revealed significant similarities to tospoviruses of the species Watermelon
      silver mottle virus and to several putative tospovirus entries in GenBank. Based
      on these alignments it is proposed to refer to all these different viruses as
      isolates of CaCV.

PMID- 16601926
TI  - Study of taurine and tauret content in the compound eye of locust with light and
      dark adaptation.
AB  - Taurine as well as tauret (retinyliden taurine) levels were measured in locust
      Locusta migratoria compound eyes. HPLC measurements revealed relatively low
      taurine levels (1.9 +/- 0.16 mM) in dark-adapted eyes. Glutamate, aspartate and
      glycine levels were 2.0 +/- 0.2, 2.7 +/- 0.4 and 3.0 +/- 0.37 mM, respectively,
      while GABA was present only in trace amounts. After about 4 h of light adaptation
      at 1500-2000 lx, amino acid levels in the compound eye were as follows: taurine,
      1.8 +/- 0.17 mM; glutamate, no change at 2.1 +/- 0.2 mM; aspartate sharply
      increased to 4.7 +/- 0.7 mM; glycine slightly decreased to 2.8 +/- 0.3 mM; and
      GABA trace levels. In the compound eye of locust Locusta migratoria, the
      existence of endogenous tauret in micro-molar range was established. In the dark,
      levels were several times higher compared with compound eye after light
      adaptation 1500 lx for 3 h, as estimated by TLC in combination with spectral
      measurements. Existence of tauret in compound eye is of special interest because
      in the compound eye, rhodopsin regeneration is based on photoregeneration.

PMID- 16601927
TI  - When quinones meet amino acids: chemical, physical and biological consequences.
AB  - Quinones and amino acids are usually compartmentally separated in living systems,
      however there are several junctions in which they meet, react and influence. It
      occurs mainly in wounded, cut or crushed plant material during harvest, ensiling
      or disintegrating cells. Diffusing polyphenols are oxidized by polyphenol
      oxidases (PPOs) to quinonic compounds, which associate reversibly or irreversibly
      with amino acids and proteins. The reaction takes place with the free
      nucleophilic functional groups such as sulfhydryl, amine, amide, indole and
      imidazole substituents. It results in imine formation, in 1,4-Michael addition
      via nitrogen or sulphur and in Strecker degradation forming aldehydes. The
      formation and activity of quinone-amino acids conjugates influences the colour,
      taste, and aroma of foods. Physical and physiological phenomena such as browning
      of foods, discoloration of plants during processing, alteration of solubility and
      digestibility, formation of humic substances, germicidal activity, cytotoxicity
      and more occur when quinones from disintegrating cells meet amino acids. The
      mechanisms of toxicity and the pathways by which PCBs may be activated and act as
      a cancer initiator include oxidation to the corresponding quinones and reaction
      with amino acids or peptides. Sclerotization of insect cuticle is a biochemical
      process involving also the reaction between quinones and amino acid derivatives.

PMID- 16601929
TI  - Cerebral cavernomas.

PMID- 16601928
TI  - Chronic intake of caffeine during gestation down regulates metabotropic glutamate
      receptors in maternal and fetal rat heart.
AB  - Caffeine is the most widely consumed substance in the world which antagonizes
      adenosine effects. Adenosine acting through A(1) receptors inhibits glutamate
      release which binds to metabotropic glutamate receptors (mGluRs). Recently, we
      have shown that maternal caffeine intake during gestation causes down-regulation
      of A(1) and metabotropic glutamate receptors in the brain of both rat mothers and
      fetuses. In the present work we provide evidence that caffeine also affects
      receptors in hearts, causing a decrease in mGluRs from both maternal and fetal
      hearts. A decrease in G(q/11) and PLC beta(1) proteins level was also observed in
      both tissues. However, phospholipase C activity was only affected in fetal heart,
      being significantly decreased. These results suggest an in vivo cross-talk
      mechanism between adenosine and glutamate receptors in peripheral tissues.
      Therefore, special attention should be paid to caffeine ingestion during
      gestation.

PMID- 16601930
TI  - Cerebral cavernomas and seizures: a retrospective study on 163 patients who
      underwent pure lesionectomy.
AB  - The objective was to evaluate the outcome of microsurgical "pure" lesionectomy in
      patients with supratentorial cavernous angiomas presenting with seizures. For
      this retrospective study 163 patients with cavernoma-related epileptic seizures
      were selected. They all underwent surgery in a single institution between 1988
      and 2003. A microsurgical frame/frameless guided minimally invasive transulcal
      "pure" lesionectomy was performed. The haemosiderin stained gliotic brain
      parenchyma that was usually found surrounding the lesion was not removed. Among
      the 99 patients with epilepsy and longer clinical history, 68 (68.7%) were found
      completely to be seizure-free, 10 (10.1%) presented sporadic and less frequent
      seizures and 17 (17.1%) remained unchanged. Sixty-three out of 64 (98.4%)
      patients who experienced only single or sporadic seizures were found to be
      completely seizure-free after surgery. Five patients were lost at follow-up (mean
      48 months, range 0.5-14 years). Long-term morbidity was 1.8%. Mortality was null.
      No haemorrhagic episodes were observed during follow-up. Pure lesionectomy
      prevents bleeding and development of epilepsy in patients that receive early
      surgery after the epileptic onset. In most of the epileptic patients with a good
      concordance between the electroclinical data and the location of the angioma,
      good results can be achieved by this kind of surgery so that more invasive and
      costly studies to find and remove the epileptogenic cerebral parenchyma seem
      justified only after lesionectomy fails.

PMID- 16601931
TI  - Chromatic pattern-reversal electroretinograms (ChPERGs) are spared in multiple
      system atrophy compared with Parkinson's disease.
AB  - Idiopathic Parkinson's disease (IPD) patients have abnormal visual evoked
      potentials (VEPs) and pattern electroretinograms (PERGs), attributed to
      dopaminergic transmission deficiency in visual pathway, probably the retina. VEP
      abnormalities are not reported in multiple system atrophy (MSA). The aim of this
      study was to investigate and compare chromatic (Ch) red-green (R-G) and blue
      yellow (B-Y), and luminance yellow-black (Y-Bk) PERGs in patients with MSA and
      IPD. We investigated 6 MSA patients (mean age: 62+/-7.4 years) not undergoing any
      pharmacological treatment, as well as 12 early IPD patients (mean age: 60.1+/-8.3
      years) and 12 age-matched normal observers. ChPERGs were recorded monocularly in
      response to full-field equiluminant R-G, B-Y and Y-Bk horizontal gratings. In MSA
      only responses to R-G stimuli showed minimal insignificant changes (slight but
      not significant amplitude reduction without any significant latency delay); no
      significant abnormality was detected for B-Y and luminance Y-Bk stimuli. By
      contrast, in IPD all responses were reduced in amplitude and delayed in latency,
      above all for B-Y stimuli. Present data indicate that both chromatic and
      achromatic PERGs are virtually unaffected in MSA, whereas in early IPD they are
      clearly impaired, suggesting different pathogenic retinal mechanisms and a useful
      simple tool for distinguishing MSA from IPD.

PMID- 16601932
TI  - Concurrent changes in shortening reaction latency and reaction time of forearm
      muscles in post-stroke patients.
AB  - The objective was to confirm the hypothesis that shortening reaction (ShoRe),
      normally occurring on forcibly shortening a muscle, is depressed or delayed in
      post-stroke patients. Eight post-stroke patients and ten age-matched normal
      subjects had a 50 degrees wrist extension or flexion induced by a torque-motor in
      the affected and the non-affected upper limb. Patients were instructed either not
      to intervene or to assist displacement (reaction-time condition, RT). Frequency
      of occurrence and latency of stretch reflex (SR) and ShoRe, and RTs were measured
      from the electromyograms (EMG) of wrist flexor (FCR) and extensor (ECR) muscles.
      SR had higher than normal frequency in both muscles. ShoRe disappeared in ECR on
      the affected side but had normal frequency in FCR of both sides. ShoRe latency
      was prolonged in FCR and ECR, in both affected and unaffected sides. RTs were
      prolonged in both FCR and ECR, in both affected and unaffected sides. Across all
      patients, RTs and ShoRe latencies in the FCR were correlated. Neither RTs nor
      ShoRe latencies were correlated to Ashworth score. RTs were inversely correlated
      to Medical Research Council scores. The decreased and delayed ShoRe in post
      stroke patients supports a role for the cortico-spinal pathway in its production
      or modulation. Monitoring of ShoRe can give insight into the recovery of the
      descending control of spinal reflexes.

PMID- 16601933
TI  - Recurrent cerebrovascular ischaemic events in patients with interatrial septal
      abnormalities: a follow-up study.
AB  - The aim of this study was to evaluate the risk of recurrent ischaemic
      cerebrovascular events (stroke or transient ischaemic attack (TIA)) in patients
      with patent foramen ovale (PFO) or atrial septal aneurysm (ASA) treated with
      different therapeutic regimens. We enrolled 86 patients aged 18-60 years with an
      unexplained ischaemic stroke or TIA referred to our inpatient department in the
      period May 1994-December 1999. Follow-up lasted until April 2003. Patients were
      excluded if the stroke or TIA was related to large-artery atherosclerosis, small
      artery occlusion, major cardiac sources of embolism or other uncommon causes.
      During a follow-up (mean+/-SD) of 64.1+/-28.8 months (range 8.1-105.6) a
      recurrent ischaemic cerebrovascular event occurred in 11/86 patients (12.8%) (5
      TIA and 6 strokes). Eight events (4 TIA, 4 strokes) occurred in the 59 patients
      with PFO alone, three (1 TIA, 2 strokes) in the 21 with PFO plus ASA and none in
      the 6 patients with ASA alone. In the overall population the cumulative risk of
      recurrent stroke/TIA was 1.2% at 2 years, 5.5% at 4 years, 7.6% at 6 years and
      23.6% at 8 years, and was similar in patients with PFO alone vs. patients with
      PFO plus ASA (9.0% vs. 6.1% at 6 years, 26.0% vs. 23.1% at 8 years; p>0.05). Nine
      cerebral ischaemic events (4 TIA, 5 strokes) occurred in the 48 patients treated
      with antiplatelet drugs (7 in patients with PFO, 2 in patients with PFO plus
      ASA), and two (1 TIA, 1 stroke) in the 17 patients treated with oral
      anticoagulants (1 with PFO, 1 with PFO plus ASA). No events occurred in patients
      submitted to transcatheteral closure.

PMID- 16601934
TI  - A further critical evaluation of requests for electrodiagnostic examinations.
AB  - The aim of this study was to evaluate the impact of electrophysiological (EDX)
      tests in the clinical management and diagnosis of patients, and the
      appropriateness of the referral diagnosis. A study was carried out in three
      electrodiagnostic services in the Torino area, over a 12-month period. In our
      study 3,900 individuals (2,340 females, 1,560 males) were evaluated. Patients
      underwent EDX examinations including nerve conduction study, electromyography and
      repetitive stimulation test. Most patients had been sent for EDX tests by
      specialists. Specialists suspected mainly polyneuropathy, whilst general
      practitioners suspected mainly carpal tunnel syndrome. Seventy-two percent of the
      requests were correctly formulated, 55% by general practitioners and 77% by
      specialists. There was a concordance between the results of the EDX tests and
      diagnostic hypothesis 40% of the time. This study confirms the usefulness and
      diagnostic impact of EDX examinations and evidences the amount of time and
      resources wasted as a result of incorrect or incomplete requests.

PMID- 16601935
TI  - An unbiased and efficient computerised tomography method to quantify muscle and
      adipose tissue volume in neuromuscular patients.
AB  - The objective was to evaluate the applicability and reliability of an unbiased
      stereological computerised tomography (CT) method for estimating total human body
      (HB), skeletal muscle (SM) and adipose tissue (AT) volumes in groups of
      neuromuscular patients. In 10 neuromuscular patients HB, SM and AT volumes were
      estimated using systematic sampling on equidistant CT sections throughout the
      total body axis using a counting grid with systematically ordered intersection
      points. Each intersection point hitting HB, SM or AT represented a known volume
      dependent on intersection point distance and sum of section thickness and gap.
      Random and systematic intra- and interobserver errors for volume estimates were
      below 0.035. These errors were negligible to the coefficient of variation of the
      group mean, being 0.190 for HB, 0.323 for SM and 0.471 for AT. Even in the
      presence of intrafascicular and intramuscular fat in neuromuscular patients,
      unbiased and reliable quantification of HB, SM and AT is possible.

PMID- 16601936
TI  - Schwannoma of the median nerve (even outside the wrist) may mimic carpal tunnel
      syndrome.
AB  - Over the last 3 years we have observed 5 cases of median nerve schwannoma that
      clinically simulated carpal tunnel syndrome (CTS). We describe the atypical
      clinical-neurophysiological picture indicating to perform ultrasonography (US).
      We retrospectively re-evaluated 5 cases of schwannoma that clinically simulated
      CTS. Five consecutive patients were referred to the neurophysiopathology
      laboratory. All patients complained of symptoms and had a neurophysiological
      examination that might have indicated CTS. Nevertheless we performed US because
      of some incongruous aspects. In cases of atypical abnormalities at
      neurophysiological and clinical examination, or dissociation between
      neurophysiological and clinical findings, physicians should consider the presence
      of a median nerve tumour. Here, US evaluation is very useful as supporting
      diagnostic methodology to assess the anatomopathological condition of the nerve
      lesion and must not be limited to the wrist.

PMID- 16601937
TI  - P300 auditory event-related potentials and neuropsychological study during
      donepezil treatment in vascular dementia.
AB  - After Alzheimer's disease (AD), vascular dementia (VaD) is the most common cause
      of dementia among the elderly. Abnormalities in neurotransmitter pathways are
      common pathogenic mechanisms shared by AD and VaD. For one month we studied the
      effects of donepezil, an acetylcholinesterase inhibitor (5 mg daily), on the
      cognitive system using P300 auditory event-related potentials (P300) and
      neuropsychological tests in 10 patients affected by probable VaD according to the
      NINDS-AIREN criteria. Our data showed a significant improvement of
      neuropsychological items and P300 latency after one month of donepezil treatment.
      In conclusion both P300 and neuropsychological tests are indicated in patients
      with VaD to confirm the efficacy of donepezil treatment during follow-up.

PMID- 16601938
TI  - MxA protein induction in MS patients treated with intramuscular IFNbeta-1a.
AB  - MxA protein production in peripheral blood leukocytes is a valuable marker to
      evaluate biologic effects of interferon-beta (IFNbeta) therapy in multiple
      sclerosis (MS) patients. The three IFNbeta preparations available in the
      treatment of MS differ with respect to antigenicity and biologic activity. We
      studied prospectively the induction of MxA protein and the development of binding
      (BAb) and neutralising antibodies (NAb) in nine relapsing-remitting MS (RRMS)
      patients during one year of intramuscular IFNbeta -1a (Avonex) treatment. Another
      nine RRMS patient treated with Avonex for 1-3.5 years were also included. The
      results were compared with our earlier published data of subcutaneous IFNbeta-1a
      (Rebif). None of these 18 patients developed NAb but three of the long-term
      patients developed BAb. The baseline MxA protein levels rose but the induction
      was weaker compared to Rebif. The stimulation index (MxA after/before IFNbeta-1a
      injection) remained elevated. Weekly intramuscular dosing of IFNbeta-1a provides
      a sustained effect on lymphocytes but differences in leukocyte stimulation may
      underlie some of the differences between IFNbeta therapies.

PMID- 16601939
TI  - Non-convulsive status epilepticus during lithium treatment at therapeutic doses.
AB  - The purpose of this study is to report the case of a patient with normal lithium
      serum levels who developed non-convulsive status epilepticus (NCSE). A 52-year
      old woman with bipolar disorder type I (DSM-IV) treated with lithium experienced
      bradypsychism and episodes of confusion and spatial disorientation without signs
      or symptoms of lithium intoxication. Lithium serum levels were in the normal
      range. A brain MR scan was negative; the electroencephalogram (EEG) revealed a
      background 3-4 Hz delta rhythm and diffuse spike discharges. Prompt EEG and
      clinical response to intravenous diazepam therapy was observed. Based on these
      findings, a diagnosis of NCSE was made and lithium therapy was withdrawn,
      resulting in symptom remission and EEG normalization. The treatment was resumed
      after two months to test the correlation between NCSE and lithium therapy.
      Resumption of therapeutic range lithium induced the same clinical symptoms and
      EEG patterns; the therapy was thus definitively discontinued. The present data
      signalling the temporal correlation of clinical and EEG changes with drug
      administration and withdrawal-suggest that even in the therapeutic range lithium
      treatment may trigger NCSE onset in predisposed subjects.

PMID- 16601940
TI  - A case of acute heart failure associated with Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is a disease of the peripheral nervous system,
      which is caused by aberrant immune responses directed against some components of
      peripheral nerves. GBS is rarely accompanied by cardiovascular involvement. We
      describe a case of acute neuropathy complicated by sudden heart failure and left
      ventricular dysfunction which had a presumably neurogenic origin. Pathogenesis of
      acute heart failure is probably due to transitorial stunned myocardium and
      neurogenic cardiac injury. We show a rare case of transitorial and acute cardiac
      dysfunction by echocardiography and laboratory markers of heart failure.

PMID- 16601941
TI  - Arachnoid cyst with intracystic haemorrhage and subdural haematoma: case report
      and literature review.
AB  - Arachnoid cysts (AC) are usually asymptomatic. However, very rarely they can
      become symptomatic due to cyst enlargement or haemorrhage, often after head
      trauma. In such cases bleeding is often confined to the subdural space, but
      intracystic haemorrhage has rarely been observed. We report a case of a child who
      had intracranial hypertension syndrome due to a right middle cranial fossa AC
      with intracystic bleeding and subdural haematoma.

PMID- 16601942
TI  - Acute myocardial infarction after sumatriptan administration for cluster
      headache.
AB  - The pain of cluster headache attacks is severe, excruciating and selectively
      responsive to subcutaneous sumatriptan. Serious cardiovascular events attributed
      to sumatriptan are extremely rare and have most often been reported in patients
      at significant cardiovascular risk, or in overt cardiovascular disease. They also
      have occurred, however, in patients without evidence of cardiovascular disease.
      We describe a 42-year-old man with episodic cluster headache without history of
      coronary artery disease who was admitted to our coronary care unit for acute
      myocardial infarction after 3 h of subcutaneous injection of sumatriptan. During
      hospitalisation cluster headache attacks were successfully treated with e.v.
      indomethacin.

PMID- 16601945
TI  - Incarcerated spigelian hernia mimicking diverticulitis: detection by
      multidetector computed tomography.

PMID- 16601946
TI  - Microbiological analysis and endoanal ultrasonography for diagnosis of anal
      fistula in acute anorectal sepsis.
AB  - BACKGROUND AND AIMS: Treatment of anorectal sepsis requires prompt surgical
      drainage, but it is important to identify any associated anal fistula for
      preventing recurrence. We evaluated whether microbiological analysis and/or
      endoanal ultrasonography could be used to predict anal fistula in patients with
      acute anorectal sepsis. METHODS: Five hundred fourteen consecutive patients with
      acute anorectal sepsis were studied. Clinical data, digital examination findings,
      endosonographic findings, and results of microbiological analysis were compared
      with definitive surgical findings of the presence or absence of anal fistula.
      RESULTS: Anorectal abscess with anal fistula was found in 418 patients, and
      anorectal abscess without anal fistula was found in 96 patients. Microbiological
      examination showed that Escherichia coli, Bacteroides, Bacillus, and Klebsiella
      species were significantly more prevalent in patients with fistula (P<0.01), and
      coagulase-negative Staphylococci and Peptostreptococcus species were
      significantly more prevalent in patients without fistula (P<0.01). Results of
      endoanal ultrasonography were concordant with the definitive surgical diagnosis
      in 421 (94%) of 448 patients studied. CONCLUSION: Acute anorectal sepsis due to
      colonization of "gut-derived" microorganisms rather than "skin-derived" organisms
      is more likely to be associated with anal fistula. When the microbiological
      analysis yields gut-derived bacteria, but no fistula has been found in the
      initial drainage operation, repeat examinations during a period of quiescence,
      including careful digital assessment and meticulous endosonography, are warranted
      to identify a potentially missed anal fistula.

PMID- 16601947
TI  - Symptom profiles and palliative care in advanced pancreatic cancer: a prospective
      study.
AB  - OBJECTIVES: To describe prospectively the prevalence and severity of disease
      related symptoms, quality of life (QOL) and need for palliative care in patients
      with advanced pancreatic cancer. PATIENTS AND METHODS: Fifty-one patients treated
      for advanced pancreatic cancer filled in the Edmonton Symptom Assessment Scale
      (ESAS) for symptom registration and the EORTC QLQ-C30 and QLQ-PAN26 quality of
      life questionnaires at first contact (baseline) and the ESAS in the following
      consultations. Need for palliative interventions were registered. RESULTS: Of the
      22 women and 29 men (mean age, 62 years), 20 had locally unresectable cancer, 19
      had metastatic disease, and 12 had recurrent disease after curative resection.
      Forty-six patients died during follow-up (median survival, 99 days). At baseline,
      patients reported significantly impaired QOL on nine of 15 scales/items (p<0.01)
      relative to the general population. Fatigue, loss of appetite, and impaired sense
      of well-being were the most troublesome symptoms on the ESAS, measured to 4.4(+/
      2.8)/5.3(+/-2.3), 4.4(+/-3.2)/5.9(+/-2.7), and 4.0(+/-2.9)/4.6(+/-2.7) (mean+/
      SD) at baseline and 8 weeks before death, respectively. Forty-four of the 51
      (86%) initial consultations and 107 (58%) of the 185 follow-ups (124 clinical and
      61 phone-calls) resulted in palliative care interventions, most frequently
      changes in opioid or laxative medication and dietary advice. CONCLUSIONS:
      Patients with advanced pancreatic cancer develop several distressing symptoms.
      ESAS was useful for assessment of symptom prevalence and intensity and is a
      clinically adequate method for symptom control. A multidisciplinary approach is
      necessary for the best palliation of symptoms at the time of diagnosis and during
      follow-up.

PMID- 16601948
TI  - The silent symptom early satiety: a forerunner of distinct phenotypes of
      anorexia/cachexia syndromes.

PMID- 16601949
TI  - Developing evidence-based guidelines for management of alimentary mucositis:
      process and pitfalls.
AB  - INTRODUCTION: It is important yet difficult to maintain currency in clinical
      oncology practice. The emergence of new diagnostic technologies and new paradigms
      for cancer treatment combine to produce a rapidly changing clinical approach to
      patients aided by the increasing use of multidisciplinary care teams and
      development of evidence-based protocols. METHODS: Teams of experts review the
      literature in a given area and produce management guidelines and protocols for
      use by practicing clinicians. Traditionally within Hematology/Oncology, these
      guidelines have been directed to management of a given tumor type. However, in
      recent years, attention has increasingly turned to supportive oncology; for
      example, there are now management guidelines for conditions such as neutropenic
      fever [Hughes et al. Clinical Infectious Diseases 34(6):730-751, 2002],
      antiemetic (The Antiemetic Subcommittee of the Multinational Association of
      Supportive Care in Cancer Annals of Oncology 17:20-28, 2006) and most recently,
      mucositis [Rubenstein et al. Cancer 100(9 Suppl):2026-2046, 2004]. It is critical
      that any guideline process should include education, evaluation, and timely
      update in its remit, because guidelines become highly compromised if their
      existence is not widely known, if they do not facilitate clinical practice, or if
      they are not reflective of contemporary medical literature. RESULTS: The
      Mucositis Study Group (MSG) of the Multinational Association for Supportive Care
      in Cancer/International Society for Oral Oncology was created in 1998 to
      specifically address the multiprofessional approach to clinical care, research,
      and education associated with mucosal injury in cancer patients. A specific
      outcome has been the development of evidence-based guidelines for the management
      of mucositis [Rubenstein et al. Cancer 100(9 Suppl):2026-2046, 2004; The
      Mucositis Study Group of MASCC/ISSO 2005]. The original guidelines [Rubenstein et
      al. Cancer 100(9 Suppl):2026-2046, 2004] and a companion paper discussing the
      science behind mucositis [Sonis et al. Cancer 100(9):1995-2025, 2004], were
      published in 2004. The MSG has recently updated the guidelines [The Mucositis
      Study Group of MASCC/ISSO 2005]. DISCUSSION: This paper discusses the process
      involved and the lessons learned that might help other groups planning to
      undertake a similar project.

PMID- 16601950
TI  - Epidemiology of treatment-associated mucosal injury after treatment with newer
      regimens for lymphoma, breast, lung, or colorectal cancer.
AB  - GOALS OF WORK: Oral and gastrointestinal (GI) mucositis are frequent
      complications of chemotherapy and radiotherapy for cancer, contributing to not
      only the morbidity of treatment but its cost as well. The risk associated with
      specific chemotherapeutic agents, alone and in combination, has been
      characterized previously. In the current study, we sought to estimate the risk
      associated with newer regimens for the treatment of non-Hodgkin's lymphoma (NHL)
      and common solid tumors. METHODS: We reviewed published studies reporting phase
      II and III clinical trials of dose-dense regimens for breast cancer and NHL, TAC
      (docetaxel, adriamycin, cyclophosphamide) chemotherapy for breast cancer, and
      infusional 5-fluorouracil-based regimens for colorectal cancer. Platinum-,
      gemcitabine-, and taxane-based regimens for lung cancer, either alone or in
      combination with radiotherapy, were also considered. Using modified meta-analysis
      methods, we calculated quality-adjusted estimates of the risk for oral and GI
      mucositis by tumor type and regimen. Case reports are used to emphasize the
      relevance of the findings for patient care. MAIN RESULTS: Our findings
      demonstrate that mucosal toxicity remains an important complication of cancer
      treatment. Moreover, innovations in drug combinations, scheduling, or mode of
      administration significantly modulate the risk for both oral and GI mucositis.
      CONCLUSIONS: Ongoing review of the clinical trial experience will remain
      important as newer, targeted agents enter standard clinical practice.

PMID- 16601953
TI  - Silver(I)-selective electrode based on [Bz2Oxo4(18)dieneS4] tetrathia macrocyclic
      carrier.
AB  - A polystyrene-based membrane of 7,8:16,17-dibenzo-6,9,15,18-tetraoxo-1,5,10,14
      tetrathiacyclooctadeca-7,16-diene [Bz2Oxo4(18)dieneS4] was fabricated using
      sodium tetraphenylborate (NaTPB) and dioctyl phthalate (DOP) as anion excluder
      and plasticizing agent. The best performance was obtained from the membrane with
      the composition ionophore [Bz2Oxo4(18)dieneS4]:polystyrene:DOP:NaTPB,
      5:100:150:10 (w/w). The response of the electrode was linear over a wide range of
      concentration, 1.26 x 10(-6)-1.00 x 10(-1) mol L(-1) for silver ion with a
      Nernstian slope of 58.4 +/- 0.1 mV per decade and a detection limit of 1.0 x 10(
      6) mol L(-1). The electrode was found to be chemically inert and of adequate
      stability with a response time of 10 s and could be used for a period of 3 months
      without change of potential. It worked satisfactorily in mixtures containing up
      to 35% (v/v) non-aqueous content. The proposed membrane sensor had good
      selectivity for Ag+ over a wide variety of metal ions in the pH range 2.2-8.5. It
      was successfully used as an indicator electrode in potentiometric titration of
      silver ion. The electrode was also useful for determination of Ag+ in waste from
      photographic films.

PMID- 16601951
TI  - Agonist effects of zinterol at the mouse and human beta(3)-adrenoceptor.
AB  - The present study investigates the action of zinterol at beta(3)-adrenoceptors.
      We used mouse primary brown adipocytes and Chinese hamster ovary (CHO-K1) cells
      expressing the mouse or human beta(3)-adrenoceptor. Zinterol was a full agonist
      at increasing cyclic AMP levels in primary brown adipocytes (which express
      beta(1)- and beta(3)-adrenoceptors but not beta(2)-adrenoceptors), and this
      effect was almost totally abolished in adipocytes derived from beta(3)
      adrenoceptor knock-out (KO) mice. Zinterol was also a full agonist at increasing
      another biological end-point, glucose uptake in brown adipocytes. This effect was
      reduced in adipocytes derived from beta(3)-adrenoceptor KO mice, with the
      remaining response sensitive to beta(1)-adrenoceptor antagonism. To determine
      whether the effect of zinterol on beta(3)-adrenoceptors in primary brown
      adipocytes can be replicated in a recombinant system, we used CHO-K1 cells
      expressing the mouse or human beta(3)-adrenoceptor. Zinterol was a full agonist
      at mouse and human receptors with respect to increasing cyclic AMP levels, with
      pEC(50) values similar to that of the selective beta(3)-adrenoceptor agonist (R,
      R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2
      dicarboxylate (CL316243) at the mouse receptor. At the human receptor, zinterol
      was more potent at increasing cyclic AMP levels than CL316243. In cytosensor
      microphysiometer studies, zinterol was a full agonist for increases in
      extracellular acidification rates at the mouse and human beta(3)-adrenoceptor.
      Therefore, we have shown that zinterol is a potent, high-efficacy beta(3)
      adrenoceptor agonist at the endogenous mouse beta(3)-adrenoceptor in primary
      brown adipocytes and at the cloned mouse and human beta(3)-adrenoceptor expressed
      in CHO-K1 cells. Zinterol is therefore one of few beta-adrenoceptor agonists with
      high potency and efficacy at the human beta(3)-adrenoceptor.

PMID- 16601954
TI  - Environmental analysis based on luminescence in organized supramolecular systems.
AB  - The use of organized supramolecular systems-including micellar media and
      cyclodextrin inclusion complexes-combined with luminescence techniques in the
      study and determination of compounds and elements of environmental interest from
      1990 to 2005 is reviewed. Analyses of environmental samples performed using
      fluorescence, photochemically induced fluorescence and phosphorescence
      spectroscopy as well as liquid chromatography, capillary electrophoresis and flow
      injection with luminescence detection in the presence of these organized media
      are described in detail.

PMID- 16601955
TI  - Isolating the whole complex of target proteins of FK506 using affinity resins
      from novel solid phases.
AB  - The development of novel solid phases enabled us to create affinity resins that
      could be used to isolate the whole complex of target proteins responsible for the
      immunosuppressive effects of FK506 from rat brain lysate, whereas the affinity
      resins from commercially available matrices could not achieve this isolation. The
      results illustrate the enhanced effectiveness of the affinity resin made from
      this novel material at identifying the target protein of the bioactive compound
      compared to resins made from the well-known materials Affigel or Toyopearl. This
      effectiveness arises because the novel material is hydrophilic enough to reduce
      nonspecific binding proteins and because it has a higher density of ligands that
      capture the nonubiquitous target protein.

PMID- 16601956
TI  - Multicenter pilot survey of resistant bacteria in the Mediterranean area.
AB  - With the aim of testing the feasibility of a multiresistant bacteria (MRB)
      surveillance methodology and evaluating the level of antimicrobial resistance and
      dissemination of resistant pathogens in the Mediterranean area, a pilot study was
      carried out in nine university hospitals in Algeria, Tunisia and France. The
      results indicate that third-generation cephalosporin-resistant Enterobacteriaceae
      comprise the major MRB in Algerian and Tunisian hospitals. In France, the highest
      incidence rates were found for methicillin-resistant Staphylococcus aureus, while
      in Tunisian hospitals, imipenem-resistant Acinetobacter baumannii seems to be a
      particularly prevalent organism. Although the data were not representative of the
      participating countries as a whole, the results show the importance and ubiquity
      of the problem in the area and the feasibility of surveillance.

PMID- 16601958
TI  - Prevention strategies in patients at high-risk for Candida infections: data from
      a neonatal intensive care setting.

PMID- 16601957
TI  - Cardiovascular protective role for activated protein C during endotoxemia in
      rats.
AB  - OBJECTIVE: We examined whether activated protein C (APC) treatment improves
      cardiovascular inflammation and dysfunction in endotoxemic rats. DESIGN AND
      SETTING: Randomized, controlled trial in an experimental laboratory of a
      university physiology department SUBJECTS: Male Sprague Dawley rats.
      INTERVENTIONS: Internal carotid artery and external jugular vein were
      catheterized under sterile conditions in rats. Instrumented rats infused or not
      with APC (240 microg/kg per hour) were challenged with E. coli endotoxin (10
      mg/kg). Four hours after endotoxin challenge rats were prepared for
      cardiovascular functional studies and tissue and blood analyses. MEASUREMENTS AND
      RESULTS: Endotoxin administration induced systemic hypotension, depression of
      myocardial systolic performance and reduction in capillary density of the small
      intestine muscularis layer. Plasma levels of nitrite/nitrate, tumor necrosis
      factor alpha and macrophage migration inhibitory factor, mesentery venule
      leukocyte-endothelium interactions, heart and small intestine myeloperoxidase
      activities were increased in endotoxin-treated rats. APC largely prevented
      endotoxin-induced cardiovascular dysfunction with improved systemic hemodynamics,
      functional capillary density, and myocardial contractile performance. Beneficial
      cardiovascular effects of APC were associated with attenuation of entotoxin
      induced inflammatory response in terms of plasma levels of nitrite/nitrate, tumor
      necrosis factor alpha, macrophage migration inhibitory factor, and endothelial
      cell-leukocyte activation. CONCLUSION: APC reduces systemic and tissue
      inflammation and preserves cardiovascular function during experimental
      endotoxemia.

PMID- 16601960
TI  - Continuous cardiac output monitoring after cardiopulmonary bypass: a comparison
      with bolus thermodilution measurement.
AB  - OBJECTIVE: The interchangeability of continuous measurement of cardiac output
      (CO) with the traditional bolus method in patients after cardiopulmonary bypass
      (CPB) is uncertain. DESIGN: Prospective observational clinical study. SETTING: A
      20-bed surgical ICU at a university hospital. PATIENTS: Fourteen deeply sedated,
      ventilated, post-cardiac surgery patients, all equipped with a pulmonary artery
      catheter. INTERVENTIONS: Six hours after the end of the CPB, 56 simultaneous
      bolus and continuous measurements were compared by a linear regression analysis
      and Bland-Altman analysis. Bolus CO was estimated by averaging triplicate
      injections of 10 ml room-temperature NaCl 0.9%, delivered randomly during the
      respiratory cycle. A stringent maximum difference of 0.55 l min(-1) (about 10% of
      the mean bolus measured) was considered as a clinically acceptable agreement
      between the two types of measurements. To be interchangeable the limits of
      agreement (+/-2 SD of the mean difference between the two methods) should not
      exceed the chosen acceptable difference. MEASUREMENTS AND RESULTS: Continuous was
      correlated with bolus CO, with a correlation coefficient of r(2)=0.68. (p<0.01).
      The Bland-Altman analysis demonstrated an objective mean bias of 0.33+/-0.6 l
      min(-1) (confidence interval of -0.87-1.58) with 34% of measured values falling
      outside of the clinically acceptable limits. CONCLUSION: Our results suggest
      that, in the first 6 h after CPB, continuous and bolus CO determinations are not
      interchangeable; one third of the values obtained by continuous CO fell outside
      the strict limits of clinically useful precision.

PMID- 16601961
TI  - Assessment of airway closure from deflation lung volume-pressure curve: sigmoidal
      equation revisited.
AB  - OBJECTIVE: To assess a sigmoidal equation for describing airway closure. DESIGN:
      Experimental study. SETTING: University laboratory. PARTICIPANTS: Eight piglets
      mechanically ventilated on zero end-expiratory pressure (ZEEP). INTERVENTIONS:
      Control and lung saline lavage. MEASUREMENTS AND RESULTS: Lungs were inflated up
      to transpulmonary pressure of 30 cmH(2)O at constant flow (0.12l s(-1)) then
      deflated at the same flow rate up to the point at which oesophageal pressure was
      constant, which was assumed to represent complete airway closure. The deflation
      volume-transpulmonary pressure curve was fitted to: (1) a sigmoidal equation
      focusing on inflexion point and pressure at maximal compliance increase and (2)
      an exponential equation above an inflexion point determined by eyeballing. Data
      deviate from the exponential equation at the point of airway closure onset. The
      zero-volume intercept was determined. Complete airway closure was reached at 
      8.3+/-3.5cmH(2)O in control conditions and at -1.3+/-3.7 cmH(2)O after lavage (p
      < 0.05). Between control and lavage, onset of airway closure was 3.0+/-1.9 vs.
      6.0+/-2.8 cmH(2)O (p <0.05), inflexion point 3.2+/-1.8 vs. 7.7+/-2.6 cmH(2)O (p
      <0.001), pressure at maximal compliance increase -1.9+/-0.7 vs. -0.03+/
      2.1cmH(2)O (p <0.05) and zero-volume intercept -1.5+/-1.4 vs. 0.3+/-2.3cmH(2)O (p
      <0.05). CONCLUSIONS: During mechanical ventilation airways stay open and close
      around ZEEP in control but are closed above ZEEP after lavage. Inflexion point
      might reflect onset of airways closure in control. Pressure at maximal compliance
      increase was not a marker of complete airways closure. In control and lavage,
      pressure at maximal compliance increase and zero-volume intercept were reasonably
      equivalent.

PMID- 16601962
TI  - Validity of medical staff assessment at admission of patient's risk of nosocomial
      infection: a prospective study in a surgical intensive care unit.
AB  - OBJECTIVE: To evaluate the ability of a surgical intensive care unit (SICU)
      medical staff to assess at admission the individual risk of nosocomial infection
      (NI) during SICU stay in patients admitted for at least 48 h. DESIGN: Prospective
      observational study. SETTING: A tertiary-care university hospital. PATIENTS AND
      PARTICIPANTS: 201 admissions to the SICU from November 19, 2003, until April 16,
      2004. MEASUREMENTS AND RESULTS: Assessment by medical staff at admission of each
      patient's estimated risk of NI (pneumonia, venous central catheter-related
      infection, symptomatic urinary tract infection, and bacteremia) during SICU
      hospitalization, in order to classify patients into four groups: NI risk very low
      or absent (group 1), low (group 2), high (group 3), very high or certain (group
      4). NI was diagnosed via routine surveillance according to Centers for Disease
      Control case definitions. RESULTS: 154 patients were assessed; the percentage of
      patients with NI increased with estimated risk at admission, from 0% in group 1
      to 14.3% in group 4. Positive predictive value of medical assessment varied from
      8.4% to 14.5%, according to the cutoff value. Negative predictive value varied
      from 92.1% to 100%. CONCLUSION: Our study suggests that ICU physicians encounter
      a major difficulty when informing patients or patients' families about the risk
      of NI occurrence, as they cannot predict this risk accurately. This limitation
      should be explained to patients and their families.

PMID- 16601963
TI  - ICU research in Denmark: difficult but possible.

PMID- 16601964
TI  - Antibacterial-coated tracheal tubes cleaned with the Mucus Shaver : a novel
      method to retain long-term bactericidal activity of coated tracheal tubes.
AB  - OBJECTIVE: To assess the long-term benefit from antibacterial coatings of the
      tracheal tube (ETT), and to keep clean the lumen of the ETT. DESIGN: Experimental
      animal study. SETTING: USA National Institutes of Health. SUBJECTS: Twelve sheep.
      INTERVENTIONS: Twelve ETTs were internally dip-coated with a silver-sulfadiazine
      in polyurethane. We developed a concentric inflatable silicone rubber "razor",
      the Mucus Shaver (MS), to shave the ETT lumen free of mucus. In a single pass, we
      cleaned all mucus from the internal surface of the ETT. CONTROL GROUP: Five
      intubated sheep were mechanically ventilated for 72 h. The ETT was suctioned
      every 6 h. STUDY GROUP: Six sheep were intubated and mechanically ventilated for
      72 h. The ETT was suctioned and cleaned with the MS every 6 h. An additional
      sheep was intubated and mechanically ventilated for 168 h. Bacteriologic studies
      and scanning electron microscopy were performed to assess bacterial colonization
      and thickness of secretions on the internal surface of the ETT. MEASUREMENTS AND
      MAIN RESULTS: In the control group, the ETT was always heavily colonized: median
      debris thickness was 380 microm, range 270-550 microm. In the study group, there
      was no colonization and no secretions in the ETT, except for three ETT that were
      colonized solely at the very tip. CONCLUSIONS: Silver-based coating of ETT
      cleaned with the MS every 6 h significantly reduces accumulation of
      mucus/secretion and bacterial growth within the ETT following 72 h of mechanical
      ventilation.

PMID- 16601965
TI  - Recognition and management of abdominal compartment syndrome in the United
      Kingdom.
AB  - OBJECTIVE: Abdominal compartment syndrome(ACS) is a condition associated with
      high mortality if undiagnosed and untreated. ACS is seen in patients managed in
      intensive care units. Very little is known on the causes, diagnosis and treatment
      of this condition in the United Kingdom. DESIGN: Questionnaire study. SETTINGS:
      222 intensive care units in the UK dealing with acute abdominal condition.
      RESULTS: 127 (57.2%) questionnaires were returned (32 from teaching hospitals and
      95 from district general hospitals. Among these, 96.9% of teaching hospitals and
      72.6% of district general hospitals had seen cases of ACS. The conditions most
      frequently associated with ACS were small and large bowel surgery (67%), vascular
      surgery (62%) and trauma (60%). ACS was suspected mainly when there was a
      distended abdomen (98.6%), oliguria (94.5%) and increased ventilatory support
      (72.2%). The diagnosis was confirmed either clinically (68.4%) or by measuring
      intra-abdominal pressure (83.7%). The commonest method for measuring intra
      abdominal pressure was the intra-vesical route. The pressure threshold for
      diagnosing the condition was variable, with a range of 11-50 mmHg. There was a
      large variation in the number of patients who were decompressed. CONCLUSION:
      Fewer patients are diagnosed with ACS in district general hospitals compared with
      teaching hospitals. The threshold for the diagnosis of ACS is variable in the UK,
      as were the numbers of patients who were decompressed, suggesting that many
      doctors are still reluctant to accept this condition. This study would suggest
      that there is a need for standardisation of diagnostic threshold and protocols
      regarding decompression in ACS.

PMID- 16601966
TI  - Sensitivity enhancement of spectral surface plasmon resonance biosensors for the
      analysis of protein arrays.
AB  - A novel method for sensitivity enhancement of spectral surface plasmon resonance
      (SPR) biosensors was presented by reducing the refractive index of the sensing
      prism in the analysis of protein arrays. Sensitivity of spectral SPR biosensors
      with two different prisms (BK-7, fused silica) was analyzed by net shifts of
      resonance wavelength for specific interactions of GST-GTPase binding domain of
      p21-activated kinase-1 and anti-GST on a mixed thiol surface. Sensitivity was
      modulated by the refractive index of the sensing prism of the spectral SPR
      biosensors with the same incidence angle. The sensitivity of a spectral SPR
      biosensor with a fused silica prism was 1.6 times higher than that with a BK-7
      prism at the same incidence angle of 46.2 degrees. This result was interpreted by
      increment of the penetration depth correlated with evanescent field intensity at
      the metal/dielectric interface. Therefore, it is suggested that sensitivity
      enhancement is readily achieved by reducing the refractive index of the sensing
      prism of spectral SPR biosensors to be operated at long wavelength ranges for the
      analysis of protein arrays.

PMID- 16601967
TI  - The use of classification methods for modeling the antioxidant activity of
      flavonoid compounds.
AB  - A study using two classification methods (SDA and SIMCA) was carried out in this
      work with the aim of investigating the relationship between the structure of
      flavonoid compounds and their free-radical-scavenging ability. In this work, we
      report the use of chemometric methods (SDA and SIMCA) able to select the most
      relevant variables (steric, electronic, and topological) responsible for this
      ability. The results obtained with the SDA and SIMCA methods agree perfectly with
      our previous model, in which we used other chemometric methods (PCA, HCA and KNN)
      and are also corroborated with experimental results from the literature. This is
      a strong indication of how reliable the selection of variables is.

PMID- 16601968
TI  - Bioactive principles in the bark of Pilidiostigma tropicum.
AB  - The crude dichloromethane bark extract of Pilidiostigma tropicum (Myrtaceae) from
      north Queensland, Australia, shows antibacterial and cytotoxic activity.
      Bioactivity-directed separation led to the isolation of rhodomyrtoxin B and
      ursolic acid-3-p-coumarate as the biologically active materials. The structures
      of these compounds were elucidated on the basis of spectral analysis. The
      intercalation interaction of rhodomyrtoxin B with DNA was investigated using
      molecular mechanics and ab initio molecular-orbital techniques. A favorable pi-pi
      interaction between rhodomyrtoxin B and the cytosine-guanine base pair is
      predicted, but the orientation of the interaction cannot be predicted based on
      frontier molecular orbitals.

PMID- 16601969
TI  - Immunolocalization of serum proteins in living mouse glomeruli under various
      hemodynamic conditions by "in vivo cryotechnique".
AB  - Distribution of serum proteins in renal glomeruli is important for histopathology
      in medical and biological fields, but mechanisms of their passage through
      glomerular capillary loops (GCL) are still difficult to clarify. We have tried to
      visualize topographical changes of the serum proteins passing through GCL by "in
      vivo cryotechnique" in combination with immunohistochemistry. Albumin and
      immunoglobulin G (IgG), Ig kappa light chain and IgG1 heavy chain were mainly
      immunolocalized in GCL, but not colocalized with zonula occludens-1 (ZO-1) under
      normotensive condition. Under heart-arrest condition and in quick-frozen fresh
      tissues, albumin and kappa light chain were immunolocalized in Bowman's space,
      indicating their passage caused by the stoppage of blood supply. However, under
      acute hypertensive condition, they were more clearly immunolocalized along
      basement membranes and in the Bowman's space, indicating their increased passage
      through GCL. IgG was also more clearly localized in mesangial areas under acute
      hypertension, compared with that under the normotensive or heart-arrest
      condition. This study is the first direct visualization for glomerular passage of
      serum proteins under abnormal hemodynamic conditions by the "in vivo
      cryotechnique", and the experimental protocol will be useful for morphofunctional
      examination of living mouse GCL and immunohistochemical analyses of dynamically
      changing proteins.

PMID- 16601971
TI  - Risks of troglitazone apparent before approval in USA.

PMID- 16601970
TI  - Histochemical analyses of living mouse liver under different hemodynamic
      conditions by "in vivo cryotechnique".
AB  - Although the morphology and molecular distribution in animal liver tissues have
      been examined using conventional preparation methods, the findings are always
      affected by the technical artifacts caused by perfusion-fixation and tissue
      resection. Using "in vivo cryotechnique" (IVCT), we have examined living mouse
      livers with histochemical, immunohistochemical and ultrastructural analyses. In
      samples prepared by IVCT, widely open sinusoids with many flowing erythrocytes
      were observed under normal blood circulation, and their collapse or blood
      congestion was seen in ischemic or heart-arrested mice. In contrast, the
      sinusoidal cavities were artificially dilated by perfusion-fixation, and
      collapsed by immersion-fixation and quick-freezing (QF) methods of resected
      tissues. The immunoreactivity of serum albumin and immunoglobulin G and intensity
      of periodic acid-Schiff-staining in hepatocytes were well preserved with the QF
      method and IVCT. Furthermore, following tissue resection, serum proteins were
      rapidly translocated into hepatocytes as demonstrated by immunoreactions on QF
      tissues frozen 1 or 5 min after resection. Translocation was not observed in IVCT
      samples, indicating that IVCT could be useful to examine cell membrane
      permeability of hepatocytes under different pathological conditions. Both dynamic
      morphology and immunodistribution of soluble components in living mouse livers,
      reflecting their physiological and pathological states, can be precisely examined
      by IVCT with higher time-resolution.

PMID- 16601972
TI  - Common variations in the ALMS1 gene do not contribute to susceptibility to type 2
      diabetes in a large white UK population.
AB  - AIMS/HYPOTHESIS: Alstrom syndrome is a rare monogenic disorder characterised by
      retinal dystrophy, deafness and obesity. Patients also have insulin resistance,
      central obesity and dyslipidaemia, thus showing similarities with type 2
      diabetes. Rare mutations in the ALMS1 gene cause severe gene disruption in
      Alstrom patients; however, ALMS1 gene polymorphisms are common in the general
      population. The aim of our study was to determine whether common variants in
      ALMS1 contribute to susceptibility to type 2 diabetes in the UK population.
      METHODS: Direct sequencing was performed on coding regions and intron/exon
      boundaries of the ALMS1 gene in 30 unrelated probands with type 2 diabetes. The
      linkage disequilibrium (LD; D' and r2) and haplotype structure were examined for
      the identified variants. The common (minor allele frequency [MAF] >5%) single
      nucleotide polymorphisms tagging the common haplotypes (tagged SNPs [tSNPs]) were
      identified and genotyped in 1985 subjects with type 2 diabetes, 2,047 control
      subjects and 521 families. RESULTS: We identified 18 variants with MAF between 6
      and 38%. Three SNPs efficiently tagged three common haplotypes (rs1881245,
      rs3820700 and rs1320374). There was no association (all p > 0.05) between the
      tSNPs and type 2 diabetes in the case-control study and minor alleles of the
      tSNPs were not overtransmitted to probands with type 2 diabetes in the family
      study. CONCLUSIONS/INTERPRETATION: Common variations in the ALMS1 gene were not
      associated with type 2 diabetes in a large study of a white UK population.

PMID- 16601973
TI  - Non-contiguous multifocal spinal tuberculosis involving cervical, thoracic,
      lumbar and sacral segments: a case report.
AB  - MAIN PROBLEM: There are only a few cases reported with non-contiguous spinal
      tuberculosis in the literature. Most of these patients have only two non
      contiguous lesions, and in almost all of these cases, surgical treatment is
      required. METHODS: A 17-year-old girl with non-contiguous multifocal spinal
      tuberculosis involving cervical, thoracic, thoracolumbar, lumbar and sacral
      segments is reported. The patient presented with systemic tuberculosis symptoms
      and signs, and progressive paraparesis. RESULTS: The patient was treated with
      antituberculous drug therapy and was operated twice for thoracolumbar and
      cervical spinal lesions. She made an excellent neurological recovery.
      CONCLUSIONS: In the patients with non-contiguous spinal involvement, there is a
      high percentage of requirement of surgical treatment. This may be due to
      "fulminant" behaviour of the disease in these patients. Early surgical treatment
      of the cases with large abscesses and systemic tuberculosis may provide early
      improvement, and must probably be the first treatment modality after general
      support to the patient.

PMID- 16601974
TI  - Residual mobility of instrumented and non-fused segments in thoracolumbar spine
      fractures.
AB  - The surgical management of thoracolumbar fractures presents potential benefits.
      However, the surgery solve the instability by fusion of mobile segments. We
      incorporate in our treatment algorithms, the use of restricted arthrodesis at
      injured levels, regardless of longer instrumentations, as well as the use of non
      fused transitory stabilizations, based on the conviction that in non-fused
      segments without traumatic disc injury, mobility persists once the
      instrumentation is removed. The goals of this study were to compare the mobility
      of non-fused segments after hardware removal to a normal range of motion and to
      find prognostic pre-op imaging patterns. We reviewed 21 consecutive patients who
      underwent surgery with preservation of mobile segments (non-fused segments
      included in the construction) in order to recover mobility after removal of
      instrumentation, performed between 1995 and 2001. All patients were treated by
      indirect reduction with posterior transpedicular instrumentation. Clinical and
      radiological outcome was analyzed after an average follow-up of 46.6 months.
      Satisfactory subjective outcome results were obtained in 94.7%. The dynamic
      radiological follow-up study showed 75% (21 segments) with normal or decreased
      range of motion (ROM) and 25% (7 segments) without mobility. The non-fused
      segments with hardware removal before 10 months of evolution presented a normal
      or decreased mobility in 83.2% while the segments with hardware removal after 10
      months showed 68.8% of mobility. The intervertebral disc (IVD)'s with normal
      initial MRI morphology preserved their mobility in 81.9%. Complications occurred
      in four patients: two superficial wound infections and two patients presented a
      late fracture of one USS Schanz. The results of this study prove that in
      thoracolumbar fractures, non-fused spinal segments included in pedicular
      instrumentation maintained mobility in a high percentage once the hardware is
      removed. 75% of the segments presented a normal or decreased ROM.

PMID- 16601975
TI  - The role of Thr5 in human neuron growth inhibitory factor.
AB  - GIF, a member of the metallothionein (MT) family (assigned as MT3), is a neuron
      growth inhibitory factor that inhibits neuron outgrowth in Alzheimer's disease.
      The conserved Thr5 is one of the main differences between GIF and other members
      in the MT family. However, natural sheep GIF has an unusual Ala5, casting doubt
      on the role of common Thr5. We constructed a series of human GIF mutants at site
      5, and characterized their biochemical properties by UV spectroscopy, circular
      dichroism spectroscopy, EDTA reaction, 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)
      reaction, and pH titration. Their inhibitory activity toward neuron survival and
      neurite extension was also examined. Interestingly, the T5A mutant exhibited
      distinct metal thiolate activity in the EDTA and DTNB reactions, and also lost
      its bioactivity. Meanwhile, the T5S mutant had similar biochemical properties and
      biological activity as wild-type human GIF, indicating the hydroxyl group on the
      Thr5 was critical to the bioactivity of human GIF. We suggest the hydroxyl group
      in human GIF may help stabilize the biologically active conformation. On the
      other hand, lack of the hydroxyl group in sheep GIF may be partially compensated
      by its abnormal structure.

PMID- 16601976
TI  - Contrast-enhanced ultrasound in non-operative management of pancreatic injury in
      childhood.
AB  - We report a 5-year-old child with pancreatic trauma from a blunt abdominal injury
      that was monitored with contrast-enhanced sonography. Unenhanced US failed to
      demonstrate the abnormality that was recognized by CT and MRI. The injury was
      well demonstrated by contrast-enhanced US which was therefore used for follow-up
      until its healing.

PMID- 16601977
TI  - Mastoid fontanelle approach for sonographic imaging of the neonatal brain.
AB  - This pictorial review describes in detail the examination technique used to study
      the neonatal brain via the mastoid fontanelle and offers a panoramic view of the
      anatomical structures that can be identified in each US slice. The brain lesions
      are grouped as congenital malformations, haemorrhage, cerebellar lesions and
      sinus venous thrombosis. In each section, the additional information obtained
      through the mastoid fontanelle is provided.

PMID- 16601978
TI  - CENP-F is a novel microtubule-binding protein that is essential for kinetochore
      attachments and affects the duration of the mitotic checkpoint delay.
AB  - Centromeric protein F (CENP-F) is a 367-kDa human kinetochore protein that was
      identified a decade ago, but its function was only recently revealed by studies
      that used small interfering RNA to deplete the protein from cells. All studies
      showed that CENP-F is important for chromosome alignment, but these studies
      differed as to whether CENP-F is important to the mitotic checkpoint. We report
      here that CENP-F is essential for cells to sustain a prolonged mitotic delay in
      response to unattached kinetochores. Cells depleted of CENP-F exit mitosis in the
      presence of defective kinetochore attachments resulting from treatment with
      nocodazole, or the depletion of kinetochore proteins CENP-E and hSgo1.
      Kinetochores depleted of CENP-F exhibited a reduction in the amounts of the
      mitotic checkpoint proteins Mad1, Mad2, hBUBR1, hBUB1, and hMps1. We postulate
      that CENP-F is not an essential component of the mitotic checkpoint but
      facilitates the duration of the mitotic delay. Separately, we show that CENP-F is
      a novel microtubule-binding protein that possesses two microtubule-binding
      domains at opposite ends of the molecule. The C-terminal microtubule-binding
      domain was found to stimulate microtubule polymerization in vitro. These
      activities provide a biochemical explanation for how CENP-F contributes to
      kinetochore attachments in vivo.

PMID- 16601979
TI  - Cystic cholangiomas after transplantation of pancreatic islets into the livers of
      diabetic rats.
AB  - Islet transplantation is increasingly used as a therapy for human type 1 diabetes
      mellitus. In our study, we investigated the effect of the transplantation of a
      low number (n = 350) of pancreatic islets into the right liver part on the
      neighboring portal bile ducts. Male streptozotocin- diabetic Lewis or autoimmune
      diabetic BB/Pfd rats (n = 1065) were subdivided into 11 experimental groups. A
      few days after low-number islet transplantation, cholangiocytes adjacent to the
      grafts showed an increase in proliferative activity. During the next 12-24
      months, many peri-insular ductules progressed via tumor-like cystic lesions to
      large cystic cholangiomas, accompanied by a translocation of the insulin receptor
      into the cytoplasm and an increase in expression of insulin-related signaling
      proteins (Insulin-receptor-substrate-1, Raf-1, Mek-1). After 24 months, 53% of
      rats with low-number transplantation exhibited at least one cholangioma >10 mm,
      significantly outnumbering tumor development in the transplant-free left liver
      part and in any control group. No cholangiocarcinomas emerged. A graft cell
      origin of the tumors was excluded by Y chromosome in situ hybridization in cross
      gender transplantations. Conclusively, low-number intrahepatic islet
      transplantation, most likely acting by permanent local hyperinsulinism, leads to
      prolonged cholangiocellular proliferation in streptozotocin- and in autoimmune
      diabetic rats, resulting in the development of benign cystic cholangiomas.

PMID- 16601980
TI  - Effect of grid laser photocoagulation in diffuse diabetic macular edema in
      correlation to glycosylated haemoglobin (HbA1c).
AB  - BACKGROUND: Glycosylated haemoglobin (HbA1c) correlates with the amount of
      hyperglycemia in diabetic patients. High HbA1c levels often predict clinically
      significant macular edema (CSME), which then needs to be treated with grid laser
      photocoagulation. The question asked in this study was whether there is a
      correlation between the effect grid laser photocoagulation in diffuse diabetic
      macular edema and HbA1c, using an optical coherence tomography (OCT) for the
      evaluation of the retinal thickness. METHODS: A prospective, non-comparative case
      series was performed to find a correlation between the effect of grid laser
      photocoagulation in diffuse diabetic macular edema and HbA1c. Thirty eyes with
      CSME of diabetic patients were included in the study. Complete ophthalmic
      examinations and OCT were performed at baseline, 1 month, 3, and 6 months after
      grid laser photocoagulation therapy. HbA1c was measured at the end of study.
      RESULTS: Significance level was set at P<0.05. A significant difference in the
      foveal (P=0.02) and superior (P=0.021) retinal thickness 6 months after laser
      therapy, no correlation between HbA1c and retinal thickness after
      photocoagulation, and an insignificant decrease in visual acuity (P=0.9) were
      found. The correlation between foveal retinal thickness and visual acuity was
      P=0.24 6 months after treatment. CONCLUSION: There was no significant correlation
      between HbA1c and the effect of grid laser photocoagulation therapy in diffuse
      diabetic macular edema. The retinal thickness decreased significantly in the
      foveal and superior area 6 months after therapy. No correlation between the
      foveal retinal thickness and the visual acuity was found. The visual acuity did
      not increase after treatment. There are many factors influencing the retinal
      thickness, such as the blood pressure and the attached posterior hyaloid.

PMID- 16601981
TI  - Inducible co-stimulator (ICOS) is upregulated in experimental autoimmune
      uveoretinitis.
AB  - PURPOSE: To study the expression of inducible co-stimulator (ICOS) and its
      association with T cell effector function in experimental autoimmune
      uveoretinitis (EAU). METHODS: Eighteen Lewis rats were immunized by retinal S
      antigen (50 microg) emulsified in complete Freund's adjuvant (CFA). Twelve normal
      rats served as normal controls and 18 receiving injection of CFA and PBS as CFA
      controls for studying the influence of CFA on the expression of ICOS in CD4+CD25+
      T cells. ICOS expression on cells from the spleens, inguinal nodes and retinae on
      day 0 (normal rats), 7, 13 and 21 was investigated using fluorescent quantitative
      real-time-PCR and Western blot. Expression of B7RP-1, an ICOS ligand, was also
      studied by Western blot. The phenotype of the cells from the aforementioned three
      tissues was identified with flow cytometry using antibodies to ICOS, CD4 and
      CD25. ICOS+ cells from the lymph nodes, and spleens on day 13 were magnetically
      sorted and cultured with S-antigen to study the cytokines production with enzyme
      linked immunosorbent assay. RESULT: An obvious uveitis was induced in all the
      immunized rats on day 13 after S-antigen immunization. The mRNA and protein of
      ICOS were scarcely detectable in normal rat spleens. In EAU rats, an up
      regulation of ICOS could be observed on day 7 and was very pronounced on day 13,
      followed by a decrease on day 21 in the spleens, draining nodes and retinae.
      Similarly, B7RP-1 expression seemed to be up-regulated during EAU. Flow cytometry
      showed that ICOS+ cells were mostly CD4 positive. Kinetics of ICOS+CD4+CD25+ T
      cells was similar to that of ICOS+ cells. CFA alone was also able to induce
      increased expression of ICOS in CD4+CD25+ T cells. IFN-gamma was secreted
      predominantly by ICOS+ T cells. CONCLUSION: ICOS expression is up-regulated in
      association with T cell effector capacity in EAU. It is presumed that the
      ICOS/B7RP-1 costimulatory pathway may play a role in the development of EAU.

PMID- 16601982
TI  - Contractile properties of skeletal muscle fibre bundles from mice deficient in
      carbonic anhydrase II.
AB  - The function of cytosolic carbonic anhydrase (CA) isozyme II is largely unknown
      in skeletal muscle. Because of this, we compared the in vitro contractile
      properties of extensor digitorum longus (EDL) and soleus (SOL) fibre bundles from
      mice deficient in CA II (CAD) to litter mate controls (LM). Twitch rise, 1/2
      relaxation time and peak twitch force at 22 degrees C of fibre bundles from CAD
      EDL [28.4+/-1.4 ms, 31.2+/-2.3 ms, 6.2+/-1.0 Newton/cm(2) (N/cm(2)),
      respectively] and CAD SOL (54.2+/-7.5 ms, 75.7+/-13.8 ms, 2.9+/-0.5 N/cm(2),
      respectively) were significantly higher compared to LM EDL (20.5+/-2.2 ms, 21.9+/
      3.7 ms, 4.5+/-0.2 N/cm(2)) and LM SOL (42.8+/-3.5 ms, 51.4+/-2.4 ms, 2.1+/-0.4
      N/cm(2)). However, in acidic Krebs-Henseleit solution, mimicking the pH, PCO(2),
      and HCO(3) (-) of arterial blood from CAD mice, twitch rise, 1/2 relaxation time,
      and peak twitch force of fibre bundles from CAD EDL (19.3+/-0.7 ms, 19.7+/-2.3
      ms, 4.8+/-0.8 N/cm(2)) and CAD SOL (41.4+/-3.6 ms, 51.9+/-5.5 ms, 2.2+/-0.7
      N/cm(2)) were not significantly different from LM fibre bundles in normal Krebs
      Henseleit solution (EDL: 19.7+/-1.1 ms, 21.6+/-0.6 ms, 4.7+/-0.2 N/cm(2); SOL:
      42.5+/-3.1 ms, 51.8+/-2.6 ms, 1.8+/-0.3 N/cm(2)). A higher pH(i) during exposure
      to acidic bathing solution was maintained by CAD EDL (7.37+/-0.02) and CAD SOL
      (7.33+/-0.05) compared to LM EDL (7.28+/-0.04) and LM SOL (7.22+/-0.02). This
      suggests that the skeletal muscle of CAD mice possesses an improved defense of
      pH(i) against elevated pCO(2). In support of this, apparent non-bicarbonate
      buffer capacity (in mequiv H(+) (pH unit)(-1) (kg cell H(2)O)(-1)) as determined
      by pH microelectrode was markedly increased in CAD EDL (75.7+/-4.1) and CAD SOL
      (85.9+/-3.3) compared to LM EDL (39.3+/-4.7) and LM SOL (37.5+/-3.8). Both latter
      phenomena may be related to the slowed rate of intracellular acidification seen
      in CAD SOL in comparison with LM SOL upon an increase in PCO(2) of the bath. In
      conclusion, skeletal muscle from mice deficient in CA II exhibits altered
      handling of acid-base challenges and shows normal contractile behavior at normal
      intracellular pH.

PMID- 16601983
TI  - Indicators of successful use of the Pavlik harness in infants with developmental
      dysplasia of the hip.
AB  - This study examined the outcomes of ultrasound-monitored Pavlik harness treatment
      in 25 infants (2 boys and 23 girls) representing a total of 31 cases of
      developmental dysplasia of the hip of Graf type IIc or more severe. For all
      infants, Pavlik harness treatment started after ultrasonographic diagnosis in our
      clinic. If there was no improvement by the third week of follow-up, the harness
      treatment was discontinued. Of the 25 patients (31 hips), 16 patients (18 hips)
      were successfully treated with the Pavlik harness. The effects of age at start of
      treatment, gender, side of pathology, first clinical evaluation findings,
      bilaterality, and Graf type on Pavlik harness treatment success were analysed. We
      found that the outcome of treatment with the Pavlik harness was related to Graf
      type, age at start of treatment, and bilaterality.

PMID- 16601984
TI  - Inflammatory infiltrate of the edges of a torn rotator cuff.
AB  - There is still considerable controversy as to whether or not the inflamed margins
      of a cuff tear should be excised during surgical suture. We have tried to
      discover whether anti-inflammatory drugs used before surgical treatment could
      resolve this issue. Thirty-eight patients were randomly either treated with an
      anti-inflammatory drug for 2 weeks or not. During the subsequent arthroscopic
      repair, a few fragments of supraspinatus edge were excised and examined
      microscopically. No significant differences emerged among samples belonging to
      the two groups. In all cases, we observed inflammatory infiltrate-lined tear
      edges. Fibrocytes and newly formed vessels were detected near the margin.
      Dystrophic calcifications were observed in both groups. Away from the edge, the
      tendon appeared hypocellular; containing areas with myxoid or fatty degeneration.
      Our study demonstrates that an anti-inflammatory drug is unable to resolve the
      inflammatory infiltrate. This failure is probably related to the poor blood
      supply to the cuff, which, in cases of rupture, is deprived of vessels coming
      from the humeral periosteum. Further studies are needed to understand how to
      eliminate the inflammatory process and clarify whether it might inhibit cuff
      healing and give rise to re-tearing of the sutured cuff.

PMID- 16601985
TI  - [Modified percutaneous balloon kyphoplasty at osteolysis of 11th thoracic
      vertebra and communication with the spinal canal. Case report and review of the
      literature].
AB  - This paper presents the case report of a 67-year-old man who came to our hospital
      suffering from severe osteolysis of the 11th thoracic vertebral body. The patient
      has been suffering from renal cell carcinoma for 2 years. During a routine
      control the above-mentioned lesion was found by chance. A few days later pain
      started in the thoracolumbar region. Treatment was intended to be palliative.
      Therefore, we looked for an option to stabilize the vertebral body as minimally
      invasive as possible. Because of a destroyed trailing edge of the vertebra,
      "normal" kyphoplasty was not possible. For this reason, we performed a
      modification, using one filled balloon as a kind of curtain between the vertebral
      body and spinal canal. With this technique we achieved an optimal filling of the
      destroyed vertebral body with cement, without any leakage. Two days
      postoperatively, the patient could leave our hospital without any pain symptoms.

PMID- 16601986
TI  - [Individualised treatment of chronic hepatitis C].
AB  - Patients infected with HCV genotype 1 are treated with a pegylated interferon
      plus ribavirin for 48 weeks, while HCV-2 or 3 infected patients are treated for
      24 weeks. Knowledge of the HCV genotype and fibrosis stage together with baseline
      viremia and the initial virologic response to therapy enables further
      individualization of the treatment duration. Non-cirrhotic patients with HCV-1
      infection, a baseline viremia < 600,000 U/ml and a rapid virologic response (< 50
      U/ml at week 4) can achieve a sustained virologic response rate of almost 90%
      with only 24 weeks of combination therapy. HCV-2 and HCV-3 infected patients with
      low baseline viremia can be treated for less than 24 weeks without compromising
      sustained virologic response rates. A longer treatment duration of up to 72 weeks
      appears reasonable for HCV-1 infected patients with serum HCV RNA levels of 50
      6,000 U/ml at week 12 of therapy.

PMID- 16601987
TI  - [The management of bleeding ulcers].
AB  - Bleeding peptic ulcers are responsible for about half of all upper
      gastrointestinal hemorrhages, one of the most frequent gastroenterological
      emergencies. In its pathogenesis, infection with Helicobacter pylori and the use
      of ulcerogenic drugs play a dominant role. Endoscopy has to be performed urgently
      when a decline in hemoglobin and/or hemodynamic instability occurs. The
      indications for local endoscopic therapy depend on the Forrest criteria, which
      include bleeding and the presence or absence of a blood clot or visible vessel.
      Local endoscopic therapy comprises injections and mechanical or thermal
      procedures. The efficacy of these procedures has been demonstrated. Additionally,
      proton pump inhibitors are administered. The prognosis for bleeding ulcers
      depends on the endoscopic findings as well as the age and comorbidity of the
      patients.

PMID- 16601988
TI  - [Lymphadenopathy and constitutional symptoms. Progress of a low-grade follicular
      lymphoma?].
AB  - Atypical presentation of Churg-Strauss syndrome includes lymph-node and
      parenchymatous organ involvement which mimics the clinical presentation of
      lymphoproliferative disorders.A 54-year old man with a history of a low-grade
      follicular lymphoma presented with rapidly growing abdominal lymph-nodes and
      hepatic, renal and pulmonary infiltrations. CT guided biopsies to verify either
      lymphoma or infections showed eosinophilic, necrotizing, granulomatous vasculitis
      leading to the diagnosis of atypical Churg-Strauss syndrome. Within a few days of
      cyclophosphamide and prednisone treatment the clinical presentation improved and
      imaging studies detected regression of all manifestations during follow-up.

PMID- 16601989
TI  - High level expression of a synthetic gene encoding Peniophora lycii phytase in
      methylotrophic yeast Pichia pastoris.
AB  - Phytase is widespread in nature. It has been used as a cereal feed additive that
      can enhance the phosphorus and mineral absorption in monogastric animals to
      reduce the level of phosphorus output in manure. Phytase of Peniophora lycii is a
      6'-phytase, which owns high specific activity. To achieve a high expression level
      of 6'-phytase in Pichia pastoris, the 1,230-bp phytase gene of P. lycii was
      synthesized and optimized for codon usage, G+C content, as well as mRNA secondary
      structures. The gene constructs containing wild type or modified phytase gene
      coding sequences under the control of the highly-inducible alcohol oxidase gene
      (AOX1) promoter, the synthetic signal peptide (designated MF4I), which is a codon
      modified Saccharomyces cerevisiae mating factor alpha-prepro-leader sequence,
      were used to transform P. pastoris. The P. pastoris strain that expressed the
      modified phytase gene (phy-pl-sh) with MF4I sequence produced 12.2 g phytase per
      liter of fluid culture, with the phytase activity of 10,540 U ml(-1). The yield
      of the modified phytase gene, with bias codon usage and MF4I signal, is 4.4 times
      higher than that of the wild type gene with MF4I signal and 13.6 times higher
      than that of the wild type gene with wild type S. cerevisiae signal. The
      recombinant phytase had one optimum pH (pH 4.5) and an optimum temperature of 50
      degrees C. The P. pastoris strain expressed the modified 6-phytase gene, with the
      MF4I signal peptide showing great potential as a commercial phytase production
      system.

PMID- 16601990
TI  - [Nicotine and the origin of cancer in the upper aerodigestive tract].

PMID- 16601991
TI  - [Quality management in the otolaryngology practice].
AB  - According to current guidelines, doctors in the German national health system are
      legally obligated to establish an internal institutional quality management (QM)
      system. By implementing a goal hierarchy and formalizing procedures according to
      the PDCA cycle and using additional specialized procedures, continuous
      improvement in patient care should be achieved. Especially ambitious practices
      wishing to obtain more rapid certification should orient themselves to the KTQ
      and QEP models. For the majority of practices, implementing a basic QM system
      without models as outlined in the G-BA guidelines is recommended. In this way,
      legal requirements can be met with less cost and effort and the most successful
      outcome is assured.

PMID- 16601992
TI  - [Secondary amaurosis after infraorbital injury with a wooden foreign body].
AB  - We report a 68-year-old male who had orbital trauma from a bicycle accident. His
      vision was initially normal but deteriorated over 8 days to complete blindness.
      After 13 days, when he first consulted a physician, clinical investigation
      revealed total ophthalmoplegia, ptosis, and chemosis. Computed tomographic scan
      showed fractures of the medial orbital wall, orbital floor, and posterior ethmoid
      with dislocation into the orbital apex near the optic nerve. The patient was sent
      to our department for optic nerve decompression. Clinical examination showed
      induration and an already healed infraorbital entry wound suggesting an orbital
      foreign body, which was confirmed by ultrasound. Renewed analysis of CT scans in
      different window settings could clearly demonstrate a wooden foreign body in the
      lower eyelid. Additionally, a diffuse inflammation in the orbital apex was
      diagnosed. The foreign body was removed and decompression of the orbita and optic
      nerve was performed. Antibiotics and corticosteroids were administered i.v.
      Unfortunately, no visual improvement could be achieved.

PMID- 16601993
TI  - [Blindness following reduction of a malar fracture].
AB  - Blindness is the most serious injury to the eye following a midfacial fracture.
      The onset of blindness complicating the midfacial fracture may be immediate (with
      the trauma), delayed (hours to days), or postoperative. The incidence of
      postoperative blindness lies between 0.3 and 8.3%. There are multiple mechanisms
      responsible for blindness but the most common reason with about 66% is probably
      increased intraorbital pressure attributable to intraorbital hemorrhage. The
      management of surgical decompression of the orbit for acute blindness is
      essential when treatment of a midfacial fracture is intended. Acute orbital
      compartment syndrome can effectively be relieved by lateral canthotomy and
      cantholysis and administration of high doses of corticosteroids. Further
      possibilities of surgical decompression of the orbit are discussed in this case
      report with postoperative irreversible blindness after reduction of a malar
      fracture and rapidly performed surgical decompression.

PMID- 16601994
TI  - [Segmental tracheal resection for the treatment of tracheal stenoses].
AB  - BACKGROUND: Segmental tracheal resection is considered to be the standard
      treatment of tracheal stenoses. MATERIALS/METHODS: During the time period 1985
      2002, segmental tracheal resection with a primary end-to-end anastomosis was
      performed in 117 patients with a cervical or upper thoracal stenosis of the
      trachea. The age distribution of the patients was between 7 and 77 years. Of the
      patients with a benign tracheal stenosis, sufficient data for a retrospective
      analysis were available in 101 patients. The length of the resected tracheal
      segments varied between 2 and 6 cm which required mobilisation of the trachea and
      the larynx and, if necessary, incision of the pulmonary ligament. RESULTS: In 5
      patients a permanent damage of the recurrent laryngeal nerve was seen, of which 4
      had undergone revision surgery and 10 months after surgery 93% presented with a
      large and stable tracheal lumen without any relevant restenosis. Due to a
      restenosis of 70-80% causing dyspnea at rest, 3% of the 101 patients had to
      undergo revision surgery. In 4% a mild and asymptomatic restenosis of 30-40% was
      seen which did not require any further treatment. CONCLUSION: These results
      demonstrate that segmental tracheal resection can safely and effectively remove
      stenotic tracheal segments of up to 6 cm and is therefore the treatment of
      choice.

PMID- 16601995
TI  - Effects of typical and atypical antipsychotics on glucose-insulin homeostasis and
      lipid metabolism in first-episode schizophrenia.
AB  - RATIONALE: Glucose and lipid metabolism dysfunction is a significant side effect
      associated with antipsychotics. Although there are many studies about the
      linkages between drugs and metabolic dysfunction, most of these studies have
      compared the effects of two antipsychotics on only one metabolic measure: either
      glucose or lipid metabolism. OBJECTIVES: The present study aimed to investigate
      the effects of clozapine, olanzapine, risperidone, and sulpiride on glucose and
      lipid metabolism in first-episode schizophrenia. MATERIALS AND METHODS: One
      hundred twelve schizophrenics were assigned randomly to receive clozapine,
      olanzapine, risperidone, or sulpiride for 8 weeks. Planned assessments included
      body mass index (BMI), waist-to-hip ratio, fasting glucose, insulin, C-peptide,
      insulin resistance index (IRI), cholesterol, and triglyceride. All measures were
      collected at baseline and at the end of the 8-week treatment. RESULTS: After
      treatment, insulin, C-peptide, and IRI were significantly increased in the four
      groups, but not fasting glucose levels. Cholesterol and triglyceride levels were
      significantly increased in the clozapine and olanzapine groups. Patients treated
      with clozapine and olanzapine had higher fasting insulin, C-peptide, and IRI
      levels than those treated with risperidone and sulpiride. Among the four
      antipsychotics, the increases of mean BMI from high to low were as follows:
      clozapine, olanzapine, sulpiride, and risperidone. CONCLUSIONS: This study
      confirmed that the four antipsychotic drugs were associated with an increase of
      insulin, C-peptide, and IRI. It was found that clozapine and olanzapine were
      associated with an increase in cholesterol and triglyceride levels. The effects
      of clozapine and olanzapine on the glucose and lipid metabolism outweighed those
      of risperidone and sulpiride.

PMID- 16601996
TI  - Increases in amphetamine-like discriminative stimulus effects of the abused
      inhalant toluene in mice.
AB  - RATIONALE: Toluene, an abused solvent, shares behavioral and pharmacological
      effects with abused depressant drugs. These effects include ethanol- and
      pentobarbital-like discriminative stimulus effects. There is also emerging
      evidence that this abused inhalant may share stimulus effects with abused central
      nervous system (CNS) stimulants. OBJECTIVE: To further explore the discriminative
      stimulus effects of one abused inhalant, this experiment evaluated the
      amphetamine-like discriminative stimulus effects of toluene. MATERIALS AND
      METHODS: Mice were trained to discriminate between d-amphetamine (1.0 mg/kg) and
      saline in a two-lever drug discrimination procedure in which responding was under
      the control of a fixed-ratio 15 schedule. Mice were tested after 10-min
      inhalation exposures to air or toluene (500-6,000 ppm) and stimulus
      generalization was examined at 0, 15, 30, 45, 60, and 75 min post-exposure.
      RESULTS: Concentration-related increases in amphetamine-lever responding were
      observed for amphetamine doses >0.56 mg/kg with full substitution occurring
      immediately after testing for 1.0 and 1.78 mg/kg. Partial amphetamine-lever
      responding was observed for all concentrations of toluene across the 75-min post
      exposure test trials. Response rates that had decreased immediately after all
      toluene exposures recovered within 15-min post exposure. CONCLUSION: This partial
      substitution of toluene for amphetamine suggests that studies of the effects of
      abused solvents on brain dopaminergic systems need to be included in the study of
      possible CNS mechanisms.

PMID- 16601998
TI  - A previously unrecognized connection between occipital condyle fractures and
      internal carotid artery injuries (carotid and condyles).

PMID- 16601997
TI  - Nitric oxide is involved in the memory facilitation induced by spermidine in
      rats.
AB  - RATIONALE: Spermidine (SPD) is an endogenous polyamine that modulates N-methyl-D:
      -aspartate receptor functions, which has been reported to facilitate memory
      formation. OBJECTIVES: In the current study, we investigated the involvement of
      nitric oxide in the facilitatory effect of SPD on the memory of adult male Wistar
      rats in the inhibitory avoidance task. RESULTS: The coadministration of the
      nonspecific NOS inhibitor N (G) nitro-L: -arginine methyl ester (L: -NAME) (0.1
      nmol, intrahippocampus) with spermidine (0.2 nmol), immediately after training,
      prevented the memory improvement caused by spermidine in the avoidance inhibitory
      task. Spermidine increased nitrite and nitrate levels (NO(X)) in the hippocampus
      30 min after its administration, and L: -NAME coinjection prevented the
      stimulatory effect of spermidine on NO(X) levels. The systemic injection of 7
      nitroindazole (30 mg/kg, i.p.), 30 min before training, impaired memory and did
      not prevent spermidine-induced increase of NO(X) levels in the hippocampus.
      CONCLUSIONS: These results suggest that memory enhancement by spermidine is
      prevented by the nonspecific nitric oxide synthase inhibitor L: -NAME.

PMID- 16601999
TI  - Effect of digital radiography on emergency department radiographic examinations.
AB  - The purpose of this paper is to determine the time-savings realized as a result
      of conversion from film-based radiography to digital radiography (DR) in
      emergency department patients receiving multiple radiographic examinations. We
      retrospectively reviewed the computer records of 69 patients from the
      preconversion group (January 2004) and 62 patients from the postconversion group
      (January 2005), calculated the mean examination time per image from each group,
      and used a one-tailed t test to compare the two means. The preconversion (a mix
      of screen-film and computed radiography) group had a mean examination time of
      3.27+/-1.50 min per image. The postconversion (DR) group had a mean examination
      time of 2.51+/-1.16 min. The p value between the two means is 0.000822 with a
      standard error of 0.330 min. DR reduces radiographic examination time by 23% when
      compared to conventional screen-film radiography.

PMID- 16602000
TI  - Heart valve donation in two small infants.

PMID- 16602001
TI  - Course of juvenile rheumatoid arthritis: social life is less affected than school
      functioning, physical activity, and well-being during a follow-up of 1.5-13
      years.

PMID- 16602002
TI  - Correlates of extracurricular sport participation among Swiss adolescents.
AB  - BACKGROUND: Based on a large national survey on the health of adolescents, this
      paper focuses on the socio-demographic and lifestyle correlates of sport practice
      among Swiss adolescents. The SMASH2002 database includes 7428 vocational
      apprentices and high school students between the ages of 16 and 20 who answered a
      self-administered anonymous questionnaire containing 565 items targeting
      perceived health, health attitudes and behaviour. Weekly episodes of
      extracurricular sport activity were measured by a four-category scale, and the
      sample was dichotomised between active (>or=two episodes of sport/week) and
      inactive (<two episodes of sport/week) respondents. Thirty percent of female
      respondents and 40.2% of male respondents reported engaging in sport activity at
      least two to three times a week; another 9.7% of the female and 19.4% of the male
      respondents reported participating in least one sport activity each day (p<0.01).
      The percentage of active respondents was higher among students than among
      vocational apprentices (p<.01), and the rates of sport activity decreased more
      sharply over time among the apprentices than among the students (p<0.01). Most
      active adolescents reported having a better feeling of well-being than their
      inactive peers [among male students: odds ratio (OR): 3.13; 95% confidence
      interval (95%CI): 1.28-7.70]. The percentage of active females who reported being
      on a diet was high, and female apprentices exhibited higher involvement in
      dieting than their inactive peers (OR: 1.68; 95%CI: 1.32-2.14). Relative to the
      inactive male respondents, the proportion of active male respondents smoking was
      lower; however, a lower proportion of the latter group did not report
      drunkenness, and the percentage of those who reported lifetime cannabis
      consumption was higher among active than inactive students (females, OR:1.57;
      95%CI:1.09-2.25; males, OR:1.80; 95%CI: 20-2.69). CONCLUSION: Organised sport
      activities should be better tailored to the work schedules of apprentices.
      Practitioners should be aware of the potential for problematic behaviour in the
      area of dieting and substance use among a subset of sport-oriented adolescents.

PMID- 16602003
TI  - Serotype distribution and antibiotic susceptibility of invasive Streptococcus
      pneumoniae disease isolates from children in Turkey, 2001-2004.

PMID- 16602004
TI  - Medullary sponge kidney associated with distal renal tubular acidosis in a 5-year
      old girl.
AB  - INTRODUCTION: Medullary sponge kidney (MSK) is characterized by cystic dilatation
      of the inner medullary collecting ducts, which causes the kidneys to resemble a
      sponge. CASE REPORT: Although distal renal tubular acidosis (dRTA) is commonly
      observed in patients with MSK, we report a 5-year-old girl with MSK who had
      features of both dRTA (nephrocalcinosis, hypercalciuria, hypocitraturia) and
      proximal tubular dysfunction (hyperuricosuria, impaired tubular phosphate
      reabsorption and proteinuria). DISCUSSION: Metabolic acidosis, hypercalciuria,
      hypocitraturia, tubular phosphate reabsorption and growth retardation in the
      patient improved with alkali therapy.

PMID- 16602005
TI  - Staphylococcus aureus epidemic in a neonatal nursery: a strategy of infection
      control.
AB  - The risk of nosocomial infection due to Staphylococcus aureus in fullterm
      newborns is higher under hospital conditions where there are overcrowded
      nurseries and inadequate infection control techniques. We report on an outbreak
      of skin infection in a Maternity Nursery (May 21, 2000) and the measures
      undertaken to bring the epidemic under control. These measures included:
      separating neonates already present in the nursery on August 23, 2000 from ones
      newly arriving by creating two different cohorts, one of neonates born before
      this date and one of neonates born later; restricting healthcare workers caring
      for S. aureus- infected infants from working with non-infected infants;
      disallowing carrier healthcare workers from caring for patients; introducing
      contact and droplet precautions (including the routine use of gowns, gloves, and
      mask); ensuring appropriate disinfection of potential sources of contamination. A
      representative number of isolates were typed by genomic DNA restriction length
      polymorphism analysis by means of pulsed-field gel electrophoresis (PFGE). Among
      the 227 cases of skin lesions, microbiological laboratory analyses confirmed that
      175 were staphylococcal infections. The outbreak showed a gradual reduction in
      magnitude when the overcrowding of the Nursery was reduced by separating the
      newborns into the two different Nurseries (two cohorts). The genotyping of the
      strains by PFGE confirmed the nurse-to-newborn transmission of S. aureus. The
      measures adopted for controlling the S. aureus outbreak can, in retrospect, be
      assessed to have been very effective.

PMID- 16602006
TI  - MTHFR 677 TT genotype in a mother and her child with Down syndrome,
      atrioventricular canal and exstrophy of the bladder: implications of a mutual
      genetic risk factor?
AB  - Apart from Husmann and Vandersteen [in: Gearhart JP, Matthews R (eds) The
      Epispadias-Exstrophy Complex. Kluwer, New York, pp 199-206, 1999], we report only
      the second case of Down syndrome (DS) associated with exstrophy of the bladder
      (EB). Besides the appearance of DS, the newborn exhibited a complete
      atrioventricular canal (CAVC) and classical EB, including diastases of the
      symphysis, an epispadic penis and an open bladder plate. Despite current
      recommendations, the mother had not supplemented her intake of folic acid during
      the periconceptional period. In a comparable case, Al-Gazali et al. (Am J Med
      Genet 103:128-132, 2001) found the homozygous 677T allele of the
      methylenetetrahydrofolate (MTHFR) gene 677C-->T polymorphism in a mother and her
      child with DS and cervical meningomyelocele. They found that the mother, who also
      had not supplemented her folic acid intake, had a secondarily altered folate
      status with an increased homocysteine level, suggesting that the homozygous TT
      mutation in the MTHFR gene in both mother and her child had contributed to the
      presentation of DS and a neural tube defect. The combined clinical findings of
      the present case and the observations of Al-Gazali et al. led us to investigate
      the 677C-->T polymorphism in our mother-child pair. Likewise we found that mother
      and child were homozygous for the mutant 677T allele. Our findings support the
      suggestion of Al-Gazali et al. that the MTHFR 677TT could be a mutual genetic
      risk factor for the co-occurrence of trisomy 21 and midline defects, the risk of
      which may be reduced by periconceptional folic acid supplementation.

PMID- 16602007
TI  - CNS-manifestation of aspergillosis in an extremely low-birth-weight infant.
AB  - Invasive aspergillosis is a rare condition in term and preterm infants. We
      present here the fatal case of a 28-week gestational age preterm baby who
      developed pulmonary, hepatic and central nervous system aspergillosis during the
      first days of life. A hyperechogenic lesion adjacent to the lateral ventricle was
      diagnosed by ultrasound and initially considered to represent periventricular
      leukomalacia. Within several days the lesion increased in size and was then
      falsely considered to be an intraventricular haemorrhage. Aspergillus fumigatus
      was ultimately isolated in the tracheal aspirates, ascites and in material
      recovered by open brain biopsy. Despite treatment with conventional and liposomal
      amphotericin B the infant patient died. CONCLUSION: Invasive aspergillosis has to
      be considered in the differential diagnosis of an unusual hyperechogenic brain
      lesion in very low-birth-weight infants with persistent symptoms and signs of
      systemic infection despite broad-spectrum antibacterial therapy. Consideration of
      this diagnosis should result in an aggressive diagnostic work-up to allow early
      initiation of an appropriate treatment.

PMID- 16602008
TI  - Disseminated nontuberculous mycobacterial infection in a child with interferon
      gamma receptor 1 deficiency.
AB  - We describe the case of a 2-year-old boy with disseminated infection by a rapidly
      growing, poorly pathogenic mycobacterial species that belonged to the
      Mycobacterium fortuitum-Mycobacterium peregrinum complex. He had a severe course
      characterized by a poor response to treatment and recurrent lymph node abscess
      formation. Sequencing of the interferon-gamma receptor 1 gene (IFNgammaR1)
      revealed that he was homozygous for a novel null mutation, 453delT. Patients
      presenting with disseminated infections by rapidly growing environmental
      mycobacteria must be investigated for complete IFNgammaR1 deficiency. The
      spectrum of IFNgammaR1 genotypes associated with this immunological disorder is
      expanding.

PMID- 16602009
TI  - Kaposi's sarcoma in a child with Wiskott-Aldrich syndrome.
AB  - INTRODUCTION: Kaposi's sarcoma (KS) is rare in childhood. It may be favored by
      acquired immune deficiencies, but the predisposing factors to KS in other
      children are unclear. DISCUSSION: KS has been reported in only two children and
      one adult with primary immunodeficiency. We report here a Tunisian child with a
      Wiskott-Aldrich syndrome who developed KS at the age of 14 months. CONCLUSION:
      This observation expands the spectrum of primary immunodeficiencies associated
      with KS in childhood.

PMID- 16602010
TI  - Aetiological heterogeneity of asymptomatic hyperglycaemia in children and
      adolescents.
AB  - INTRODUCTION: Randomly estimated fasting hyperglycaemia in an asymptomatic
      individual may represent the first sign of pancreatic beta-cell dysfunction.
      OBJECTIVE: We aimed at specifying the genetic aetiology of asymptomatic
      hyperglycaemia in a cohort of children and adolescents. SUBJECTS AND METHODS: We
      analysed the aetiological diagnosis in 82 non-obese paediatric subjects (38
      males) aged 0.2-18.5 years (median: 13.1) who were referred for elucidation of a
      randomly found blood glucose level above 5.5 mmol/l. In addition to fasting
      glycaemia and circulating levels of insulin and C-peptide, the subjects were
      tested by an oral glucose tolerance test and an intravenous glucose tolerance
      test and screened for mutations in the genes encoding glucokinase (GCK), HNF
      1alpha (TCF1), Kir6.2 (KCNJ11) (if aged <2 years) and HNF-4alpha (HNF4A) (those
      with a positive family history of diabetes). RESULTS AND DISCUSSION: We
      identified 35 carriers of GCK mutations causing MODY2, two carriers of TCF1
      mutations causing MODY3, one carrier of a HNF4A mutation causing MODY1 and one
      carrier of a KCNJ11 mutation causing permanent neonatal diabetes mellitus. Of the
      remaining patients, 11 progressed to type 1 diabetes mellitus (T1DM) and 9 had
      impaired glucose tolerance or diabetes mellitus of unknown origin. In 23
      subjects, an impairment of blood glucose levels was not confirmed. We conclude
      that 39 of 82 paediatric patients (48%) with randomly found fasting
      hyperglycaemia suffered from single gene defect conditions, MODY2 being the most
      prevalent. An additional 11 patients (13%) progressed to overt T1DM. The
      aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is
      a clue to introducing an early and effective therapy or, in MODY2, to preventing
      any future extensive re-investigations.

PMID- 16602012
TI  - Fatal coronary artery anomaly presenting as bronchiolitis.

PMID- 16602013
TI  - Schnitzler's syndrome: 3-year radiological follow-up.
AB  - Schnitzler's syndrome comprises urticaria, monoclonal gammapathy, inflammatory
      signs (fever, enlarged lymph nodes, hyperleukocytosis), and bone lesions. We
      report the imaging findings and follow-up of a new case with extensive
      osteosclerosis of the iliac bone, associated with inflammatory signal changes on
      MRI and foci of increased uptake on bone scintigraphy. When a diagnosis of
      Schnitzler's syndrome is established, treatment should be towards symptoms only;
      a long follow-up is warranted, as a delayed evolution towards a
      lymphoproliferative syndrome is possible.

PMID- 16602014
TI  - An extrarenal rhabdoid tumor of the cervical spine with bony involvement.
AB  - A case of a histologically proven rhabdoid tumor of the cervical spine in a 19
      year-old Caucasian male is presented. Primary extrarenal rhabdoid tumors are very
      rare. When the central nervous system is involved, the tumor usually is located
      in the brain. Only three cases of primary spinal rhabdoid tumor have been
      reported. This case is the first reported extradural rhabdoid tumor of the spinal
      canal and the first case of a rhabdoid tumor located in the spinal canal with
      bony involvement.

PMID- 16602015
TI  - Fibrous dysplasia localized to spine: a diagnostic dilemma.
AB  - Fibrous dysplasia of the spine is uncommon, especially in monostotic form.
      Isolated vertebral involvement in polyostotic form is very rare. We report a case
      of polyostotic fibrous dysplasia with lesions localized to dorso-lumbar spine in
      a 45-year-old rheumatoid arthritis patient. No associated appendicular lesions,
      cutaneous manifestations or endocrinopathies were seen. The extreme rarity of
      this type of lesion can pose a diagnostic dilemma, and biopsy is required for
      diagnosis. The association with rheumatoid arthritis in our case seems to be a
      chance occurrence.

PMID- 16602016
TI  - Relationship between low back pain, disability, MR imaging findings and health
      care provider.
AB  - OBJECTIVE: To determine the association between the self-report of pain and
      disability and findings on lumbar MR images, and to compare two different health
      care providers in Spanish patients with low back pain (LBP). DESIGN: Cross
      sectional MATERIAL AND METHODS: A total of 278 patients, 137 men and 141 women
      aged 44+/-14 years submitted with low back pain (LBP) were studied. One hundred
      and nine patients were from the National Health System (NHS) and 169 from private
      practice. Patients with previous discitis, surgery, neoplasm or traumatic
      episodes were excluded. Every patient completed a disability questionnaire with
      six core items, providing a score of disability from 2 to 28. All patients had
      sagittal spin-echo T1 and turbo spin-echo T2, axial proton-density and MR
      myelography weighted images. MR images of the two most affected disc levels were
      read, offering an MR imaging score from 0 to 30. RESULTS: Patients with a
      combination of LBP and sciatica showed the highest levels of disability
      (p=0.002). MR imaging scores only correlated with pain interference with normal
      work (p=0.04), but not with other disability questions. Patients from the NHS
      showed greater disability scores than private ones (p=0.001) and higher MR
      imaging scores (p=0.01). CONCLUSION: In patients with LBP, MR imaging only
      correlates with pain interference with work but not with other disability
      questions. Differences are found between private and NHS patients, the latter
      being more physically affected.

PMID- 16602017
TI  - Nora's lesion, a distinct radiological entity?
AB  - OBJECTIVE: To describe the radiological findings of "Bizarre parosteal
      osteochondromatous proliferation"(BPOP)-otherwise known as Nora's lesion, to
      describe the natural evolution of BPOP and to assess radiologically if BPOP is
      indeed part of a spectrum of reactive lesions including florid reactive
      periostitis and turret exostosis. DESIGN: Four experienced musculoskeletal
      radiologists studied plain radiographs and other imaging documents of
      histologically-proven Nora's lesions, looking for soft-tissue changes, periosteal
      reaction/calcification and calcified/ossified pseudotumours, and compared those
      findings with findings on pathology reviewed by a peer group of pathologists.
      PATIENTS: Twenty-four Nora's lesions originating from a series of 200
      consecutive, histologically-verified bone (pseudo)tumours of the hand, seen by
      the "Netherlands Committee on Bone Tumours" for review and second opinion.
      RESULTS: Nora's lesions have a recognised presentation on radiographs without
      specific MR characteristics. Natural evolution could be assessed retrospectively
      in four cases. Recurrent lesions were seen in seven cases and are difficult to
      differentiate from primary lesions. CONCLUSIONS: Nora's lesion, defined as a
      "well-marginated mass of heterotopic mineralization arising from the periosteal
      aspect of an intact cortex, without medullary changes" has a distinct
      radiological presentation and is part of a spectrum of reactive lesions which
      includes florid reactive periostitis and turret exostosis. As it has a distinct
      radiological appearance, differential diagnosis of malignant lesions such as
      osteosarcoma and chondrosarcoma should be clear. It does not require immediate
      biopsy unless the natural evolution is unspecific.

PMID- 16602018
TI  - Spastin, the most commonly mutated protein in hereditary spastic paraplegia
      interacts with Reticulon 1 an endoplasmic reticulum protein.
AB  - Spastin, an ATPase belonging to the AAA family of proteins is most commonly
      mutated in autosomal dominant hereditary spastic paraplegias (HSP). Spastin is a
      multifaceted protein with versatile role in cellular events, principally involved
      in microtubule dynamics. To gain further insight into the molecular function of
      spastin, we used the yeast two-hybrid approach to identify novel interacting
      partners of spastin. Using spastin as bait, we identified reticulon 1 (RTN1) and
      reticulon 3 (RTN3) as potential spastin interacting proteins. RTN1 and RTN3
      belong to the reticulon (RTN) gene family, which are primarily expressed in the
      endoplasmic reticulum. Moreover, RTN1 is known to play a role in vesicular
      transport processes. Using in vitro and in vivo immunoprecipitation experiments,
      we were able to demonstrate that RTN1 interacts specifically with spastin.
      Intracellular distribution studies using immunostaining and overexpression of
      epitope-tagged protein revealed an obvious colocalization of spastin and RTN1 in
      discrete vesicles in the cytoplasm. Spastin mediates its interaction with RTN1
      through its N-terminal region containing a microtubule-interacting and
      trafficking domain. It is interesting to note that the aberrant intracellular
      distribution of a truncated spastin protein was rescued by coexpression with
      RTN1, which highlights the physiological significance of this interaction. Our
      findings strengthen the hypothesis that disruption of intracellular vesicular
      transport processes could cause HSP. It is interesting to note that RTN1 is
      localized to 14q23.1 where SPG15 locus was mapped. Therefore, we considered RTN1
      as a candidate gene for the SPG15 locus, but our mutational analysis possibly
      excludes RTN1 as causative gene.

PMID- 16602020
TI  - Spermiogenesis in the caryophyllidean cestode Khawia armeniaca (Cholodkovski,
      1915).
AB  - Spermiogenesis of the monozoic cestode Khawia armeniaca (Cholodkovski, 1915), a
      parasite of Capoeta capoeta sevangi (De Filippi, 1865) (Pisces: Cyprinidae), has
      been investigated by means of transmission electron microscopy for the first
      time. The present results show that the type of spermiogenesis in K. armeniaca
      shares the main features described previously in the pseudophyllideans and/or
      spathebothriideans: apical dense material in the zone of differentiation in the
      early stages of spermiogenesis, rotation of flagellum and flagellar bud,
      proximodistal fusion, and penetration of the nucleus into the spermatid body
      after the fusion of the free flagellum with the MCP has started. However, only
      one axoneme and a simple intercentriolar body represent presumably more evolved
      characters, typical for "higher" tapeworms. Ultrastructural data of
      spermiogenesis in K. armeniaca may support the hypothesis that the Caryophyllidea
      are secondarily derived from an ancestor closely allied with the Pseudophyllidea.

PMID- 16602019
TI  - Inhibitory effects of L- and T-type calcium antagonists on contractions of human
      detrusor muscle.
AB  - The inhibitory and relaxant effects of the L-type calcium antagonists nifedipine,
      nimodipine, verapamil and diltiazem, and of the T-type calcium antagonist
      mibefradil, on contractions of isolated human detrusor muscle were investigated.
      The tissue was obtained from 10 patients undergoing cystectomy due to bladder
      cancer. Effects of the calcium antagonists at different concentrations on the
      concentration-response curves for carbachol were investigated. Furthermore,
      concentration-relaxation curves were performed using potassium-precontracted
      muscle strips. All L-type calcium antagonists suppressed the mean concentration
      response curve of carbachol significantly at a concentration of 10(-6) M.
      Mibefradil up to 10(-5) M did not significantly suppress it. Nifedipine
      significantly reduced the carbachol-induced maximum contraction to 75% and 44%,
      verapamil to 75% and 67% of the appropriate control value at concentrations of
      10(-7) and 10(-6) M, respectively. Diltiazem reduced it insignificantly to 96%
      and 71% at the above-mentioned concentrations. The concentration-relaxation
      experiments revealed following pD2-values and maximum relaxations of nifedipine,
      nimodipine, verapamil and diltiazem, respectively: 6.23, 6.37, 5.66, 5.81 and
      85%, 83%, 82%, 90%. Maximum relaxations and pD2-values were not significantly
      different from each other. The lowest concentration, for which a significant
      effect compared to control in Student;s t-test was found, amounted to 10(-10) M,
      10(-9) M, 10(-7) M, 10(-6.5) M and 10(-4) M for nimodipine, nifedipine,
      diltiazem, verapamil and mibefradil, respectively. L-type calcium antagonists are
      very potent relaxant agents of the human detrusor muscle in vitro.

PMID- 16602021
TI  - Homocysteine, folate, lipid profile and MTHFR genotype and disability in children
      with myelomeningocele.
AB  - STUDY DESIGN: We performed a cross-sectional study in myelomeningocele children.
      OBJECTIVE: To investigate plasma total homocysteine, folate, lipid profile, 5,10-
      metylenetetrahydrofolate reductase genotype (MTHFR) and disability. MATERIALS AND
      METHODS: Sixty patients aged between 2 and 14 years with myelomeningocele (18
      ambulatory and 42 non-ambulatory) and 150 healthy children of same age, are
      investigated for lipid profile, homocysteine concentration and for the
      determination of MTHFR genotype. RESULTS: Plasma homocysteine concentrations were
      significantly higher in myelomeningocele children than in the control group. In
      myelomeningocele female group, there were higher levels of total cholesterol and
      very-low-density lipoprotein cholesterol with respect to the control group.
      Myelomeningocele children walking with tutorial aid showed triglyceride levels
      significantly lower than those observed in myelomeningocele non-walking children.
      CONCLUSION: Disability, insulin uptake, lipid, homocysteine, hormones plasma
      levels, and genetic factors such as allelic variants of MTHFR are possible for
      cardiovascular disease in myelomeningocele children. This study highlights the
      importance of a continuous surveillance of any changes in the lipid profile that
      should be corrected as soon as possible. Constant physical activity necessary to
      increase HDL levels should be planned in all susceptible children. Nonetheless,
      further investigations are necessary to identify new homocysteine susceptible
      genes for prevention of early atherosclerosis and consequent cardiovascular
      disease.

PMID- 16602022
TI  - [Planning of orthopedic surgery for rheumatoid arthritis].
AB  - The inflammatory process in rheumatoid arthritis is progressive and ends in
      destruction of the cartilage. Subsequent instability and mutilation of the joint
      might happen. The classification of destruction can be done by X-rays and
      assessment of the clinical picture. Depending on the radiologic stage different
      therapy concepts, ranging from conservative to operative, are established. It is
      the aim of surgery to restore motion and function in a painless joint. Surgery
      can be done to prevent the joint from further destruction or to replace the joint
      after resection. Different concepts based on radiologic findings are presented in
      this review.

PMID- 16602023
TI  - Intracranial complications of chronic otitis media.

PMID- 16602024
TI  - Early scrotal exploration in all cases is the investigation and intervention of
      choice in the acute paediatric scrotum.
AB  - The acute scrotum in the paediatric population is a clinical dilemma where a
      definitive diagnosis can only truly be made at surgical exploration. We postulate
      that surgical exploration in all cases allows truly accurate diagnoses, treats
      the torted appendage testes and enables the validity of clinical signs associated
      with scrotal pathology to be assessed. We retrospectively reviewed all boys less
      than 15 years old who presented to our institution with scrotal pain over a 2
      year period. A total of 121 patients attended of whom 113 had exploratory
      surgery, 31 (27%) had testicular torsion, 64 (57%) had a torted appendage testis,
      12 (11%) had epididymitis, 1 (1%) had fat necrosis and 5 (4%) had no abnormality
      detected. On exploration 9 (29%) of the torted testis were unsalvageable and thus
      required excision. The initial clinical impression was frequently demonstrated to
      be flawed. Two patients with testicular torsion presented with a painless
      swelling and two further patients had necrotic testes despite a history of pain
      for less than 4 h. A normal cremasteric reflex and a visible blue dot were
      detected in boys with testicular torsion. Doppler ultrasound scans were not
      reliable with 50% sensitivity to clearly differentiate between torsion of the
      testis and that of the appendage testis. Absolute dependence on clinical features
      can lead to a misdiagnosis of testicular torsion. The surgical treatment of
      torted appendage testis is safe, allowing accurate diagnosis and pain relief with
      minimal morbidity. Early scrotal exploration of all cases with testicular pain
      ensures maximal testicular salvage.

PMID- 16602025
TI  - Surgical treatment of multiple knee ligament injuries in 44 patients: 2-8 years
      follow-up results.
AB  - The purpose of the study was to evaluate the mid-term results of surgical
      treatment in different groups of patients with multiple knee ligament injuries.
      Review of our patients' records revealed that 48 acute and chronic patients were
      surgically treated for combined knee injury. Due to severe capsular damage in
      these injuries, open techniques were used. In our treatment protocol, avulsed
      ligaments and tears of the posterolateral and posteromedial corner were repaired
      if possible, whereas midsubstance tears of cruciate ligaments and chronic cases
      were reconstructed with autografts. Postoperatively, an accelerated program of
      rehabilitation was introduced, aiming to progressively mobilize the joint and
      improve muscle endurance. For the follow-up evaluation we designed a protocol
      composed of two parts. In the first part, anatomical lesions were recorded and in
      the second part, clinical evaluation was performed using the Lysholm score, the
      Tegner rating system, the IKDC evaluation form, and the KT1000. Student's t tests
      and chi-square tests were used for data analysis. Forty-eight patients (mean age
      28.6+/-11.9 years; 41 males) were classified according to the specific anatomical
      structures involved. Group A included 12 anterior cruciate ligament (ACL) and
      medial structure injuries, group B included 11 ACL or posterior cruciate ligament
      (PCL) ruptures combined with posterolateral injuries, and group C consisted of 25
      knee dislocations (ACL and PCL ruptures which might be combined with damage of
      the collateral ligaments). Thirty-eight patients were surgically treated during
      the acute phase and ten patients were treated chronically. Forty-four patients
      (91.6%) were followed up at a mean of 51.3+/-29.9 months. Average Lysholm score
      was 87+/-12.3; average Tegner score was 5.09+/-2.19 before accident and 4.34+/
      2.12 in re-examination; IKDC score was A in 10 cases, B in 22, C in 6, and D in
      6. The mean range of motion was 129.9 degrees +/-12.5 degrees . The average loss
      of extension and flexion were 1.6 degrees +/-2.5 degrees and 7.6 degrees +/-7.9
      degrees , respectively. The side-to-side difference in corrected anterior and
      posterior translation in quadriceps neutral angle and in anterior translation in
      30 degrees angle was <3 mm for about 65% of our patients. Surgical treatment of
      multiple knee ligament injuries, using autografts, provided satisfactory
      stability, range of motion, and subjective functional results. However, despite
      the improvement of the quality of life, the preinjury patients' activity level
      was not fully obtained in re-examination. Patients underwent surgical treatment
      during the acute phase had better scores in several points, but finally there was
      no statistical significance between acute and chronic patients. Moreover, no
      statistically significant differences were observed among the groups with
      specific damaged anatomical structures.

PMID- 16602026
TI  - Phlorotannins as radical scavengers from the extract of Sargassum ringgoldianum.
AB  - To screen algal phlorotannins with antioxidative activities, 50% ethanol extracts
      of 25 Japanese marine algae were evaluated. Scavenging activity against
      superoxide anion radicals was frequently found with a high content of total
      phenolic compounds. Among these, the extract from the brown seaweed, Sargassum
      ringgoldianum, showed the strongest scavenging activity. The active fraction
      contained a mixture of high molecular weight polyphenols, phlorotannins that were
      found to be polymerized bifuhalol, as analyzed by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The
      scavenging activity of the fraction against superoxide anion radicals was
      estimated to be 1.0 microg/ml (IC(50)), which were approximately five times
      stronger than that of catechin.

PMID- 16602027
TI  - Axillary artery to right atrium shunt for hemodialysis access in a patient with
      advanced central vein thrombosis: a case report.
AB  - Central venous thrombosis presents a challenge to the treatment of hemodialysis
      patients requiring vascular access. We present the case of a patient with renal
      failure and virulent thrombophilia causing severe central venous thrombosis. We
      discuss the use of a hemodialysis shunt from the right axillary artery to the
      right atrium and describe the technical details and the pitfalls encountered in
      our utilization of this technique.

PMID- 16602028
TI  - Conservative treatment of an early aortic graft infection due to Acinetobacter
      baumanii.
AB  - Acute infection of an aortic graft is a devastating complication. While resection
      of the infected prosthesis and extra-anatomic bypass is the established
      treatment, this carries a high mortality. We describe a case of early aortic
      graft infection with the unusual organism Acinetobacter baumanii, which was
      eradicated by a combination of surgical drainage and antibiotics, allowing
      preservation of the graft. The patient remains well 30 months later.

PMID- 16602029
TI  - Influence of indomethacin in the rat aneurysm model.
AB  - The objective of this study was to trigger the formation of rat abdominal aortic
      aneurysm by applying calcium chloride periarterially and then to detect the
      degree of prevention of aneurysm occurrence by oral introduction of indomethacin
      in some of the rats. Thirty-one rats were divided into three groups. The
      infrarenal aorta above the iliac bifurcation of rats was treated with sodium
      chloride in group 1 (control, n = 7), calcium chloride in group 2 (n = 12), and
      calcium chloride-indomethacin in group 3 (n = 12) periarterially. The rats of
      each group were randomly selected at the end of the first, second, and third
      weeks postoperatively; and vessel diameters of abdominal aortas were measured by
      digital photography using a micrometer. Aneurysmal development was not observed
      in any of the rats in the control group. None of the comparisons was
      statistically significant (p > 0.05). Aneurysmal development was observed in all
      of the rats in the calcium chloride group. Results from the first, second, and
      third weeks postoperatively were statistically significant (p < 0.05). A middle
      aneurysmal development was observed in all rats in the calcium chloride
      indomethacin group. Only results from the second and third weeks postoperatively
      were statistically significant (p < 0.05). Measurements in groups 2 and 3 were
      statistically significant when compared to group 1 (p < 0.001). However, the mean
      increase in the indomethacin-treated group (group 3) was only 26.1%. The
      macroscopic appearance of the control group and an aneurysm induced by calcium
      chloride application are shown.

PMID- 16602030
TI  - Identification and characterization of genes induced for anthocyanin synthesis
      and chlorophyll degradation in regenerated torenia shoots using suppression
      subtractive hybridization, cDNA microarrays, and RNAi techniques.
AB  - Anthocyanin synthesis and chlorophyll degradation in regenerated torenia (Torenia
      fournieri Linden ex Fourn.) shoots induced by osmotic stress with 7% sucrose were
      examined to identify the genes regulating the underlying molecular mechanism. To
      achieve this, suppression subtractive hybridization was performed to enrich the
      cDNAs of genes induced in anthocyanin-synthesizing and chlorophyll-degrading
      regenerated shoots. The nucleotide sequences of 1,388 random cDNAs were
      determined, and these were used in the preparation of cDNA microarrays for high
      throughput screening. From 1,056 cDNAs analyzed in the microarrays, 116
      nonredundant genes were identified, which were up regulated by 7% sucrose to
      induce anthocyanin synthesis and chlorophyll degradation in regenerated shoots.
      Of these, eight genes were selected and RNAi transformants prepared, six of which
      exhibited anthocyanin synthesis inhibition and/or chlorophyll degradation in
      their leaf discs. Notably, the RNAi transformants of the glucose 6
      phosphate/phosphate translocator gene displayed inhibition both of anthocyanin
      synthesis and chlorophyll degradation in both leaf discs and regenerated shoots.
      There was also less accumulation of anthocyanin in the petals, and flowering time
      was shortened. The genes we identified as being up-regulated in the regenerated
      torenia shoots may help further elucidate the molecular mechanism underlying the
      induction of anthocyanin synthesis and chlorophyll degradation.

PMID- 16602031
TI  - Immunological basis for IgE hyper-production in enfuvirtide-treated HIV- positive
      patients.
AB  - We previously reported that enfuvirtide (ENF) treatment is accompanied by a
      selective increase of serum IgE. We asked whether ENF had intrinsic capability to
      direct B-lymphocytes to switch to IgE and/or if it could drive CD4 T cells to a
      Th2 phenotype. ENF was added in vitro: (a) to B-lymphocytes stimulated with IgE
      switch inducing stimuli; (b) to peripheral blood mononuclear cells. Total IgE
      production by B cells and IL4 and IFN-gamma production by CD4 T lymphocytes were
      evaluated, respectively. ENF had no measurable effect on the IgE production by B
      lymphocytes. In contrast, it sharply increased the IL4 to IFN-gamma (a correlate
      of the Th2 phenotype) when added in vitro to T cells from healthy donors or from
      single ENF-treated patients. The hyper-IgE production in ENF-treated patients is
      associated with the in vitro induction of a type-2 phenotype in CD4 T cells.

PMID- 16602032
TI  - Aberrant expression of CC and CXC chemokines and their receptors in patients with
      asthma.
AB  - This study further elucidates the roles of selected chemokines (IP-10, MIG, and
      RANTES) and their receptors (CCR3, CCR5, and CXCR3) in asthma. We compared their
      profiles in six groups of participants-atopic cohort and nonatopic cohort (each
      including controls and asthmatic patients with or without steroid therapy).
      Plasma concentration of IP-10 was significantly lower while that of RANTES and
      the expression of CCR3 were higher in asthmatic patients (all p < 0.05). Plasma
      RANTES correlated positively with the GINA severity score in all asthmatic
      patients (r=0.27, p < 0.05), and with IL-13 in nonatopic asthmatic patients
      (r=0.46, p < 0.05). In asthmatic patients, the ex vivo release of IP-10 and MIG
      was attenuated in PBMC activated with allergen, mitogens and IL-18 (p < 0.05). In
      conclusion, plasma RANTES may be a surrogate marker for asthma and the diminished
      Th1 related CXC chemokine production may contribute to Th2 predominance in
      asthma.

PMID- 16602033
TI  - Self-reactive CD4+ T cells and B cells in the blood in health and autoimmune
      disease: increased frequency of thyroglobulin-reactive cells in Graves' disease.
AB  - The mechanisms underlying activation of potentially self-reactive circulating B
      cells and T cells remain unclear. We measured the uptake of a self-antigen,
      thyroglobulin, by antigen presenting cells, and the subsequent proliferation of
      CD4(+) T cells and B cells from healthy controls and patients with autoimmune
      thyroiditis. In Hashimoto's thyroiditis, B cells bound increased amounts of
      thyroglobulin in a complement- and autoantibody-dependent manner, and the
      thyroglobulin-elicited proliferation of CD4(+) T cells and B cells was complement
      dependent. Increased proportions of Tg-responsive CD4(+) T cells and B cells were
      found in patients with Graves' disease. Notably, both patient groups and healthy
      controls exhibited higher proliferative responses to thyroglobulin than to a
      foreign recall antigen, tetanus toxoid. Our results suggest that self-tolerance
      can be broken by exposure of circulating lymphocytes to high local concentrations
      of self-antigen, and that complement plays a role in the maintenance of
      autoimmune processes, at least in Hashimoto's thyroiditis.

PMID- 16602034
TI  - 'Autistic' traits in non-autistic Japanese populations: relationships with
      personality traits and cognitive ability.
AB  - We explored the relationships between 'autistic' traits as measured by the AQ
      (Autism-Spectrum Quotient; Baron-Cohen et al., J. Autism Develop. Disord. (2001b)
      31 5) and various personality traits or cognitive ability, which usually coincide
      with autistic symptoms, for general populations. Results showed the AQ was
      associated with tendencies toward an obsessional personality as defined by the
      TCI (Temperament and Character Inventory), higher depression and anxiety, and
      higher frequency of experience of being bullied. These results parallel the
      patterns in autism and corroborate the validity of the AQ for general
      populations. Contrary to our prediction, however, there was no relationship
      between the AQ and cognitive ability, such as theory of mind, executive
      functioning, and central coherence, suggesting the AQ does not reflect autism
      specific cognitive patterns in general populations.

PMID- 16602035
TI  - A case of partial trisomy of chromosome 8p associated with autism.
AB  - We report on a case of a 6-year-old female with partial trisomy 8p(21-23)
      associated with autism, mild dysmorphic features, and moderate learning
      disability. Although mental retardation is a common finding in patients with
      mosaic trisomy 8 or partial trisomy of various regions of chromosome 8, only two
      cases associated with autism have been reported so far. Also, in our case
      clinical manifestations were mild compared to other patients with duplication of
      the same region of chromosome 8. Although there has been no strong evidence for
      linkage on chromosome 8 in any of the genome-wide linkage studies so far, the
      possibility that this segment includes genes involved in the etiology of autism
      should be further explored.

PMID- 16602036
TI  - Helicobacter pylori infection is the major risk factor for gastric inflammation
      in the cardia.
AB  - We attempted to clarify the pathogenesis of gastric inflammation in the cardia.
      Eighty Japanese participated in this study. Biopsy specimens of the gastric
      antrum, corpus, and cardia (1 cm from the squamocolumnar junction) were obtained,
      and histological gastritis was evaluated. Cardiac inflammation was also evaluated
      using magnifying gastroscopy. We examined Helicobacter pylori infection, gastric
      juice pH/bile acid (BA), serum pepsinogen and gastrin levels, gastroesophageal
      reflux disease (GERD), and habitual smoking and assessed the relations between
      these factors and cardiac inflammation. The prevalence of H. pylori infection was
      statistically higher in patients with cardiac inflammation than in those without
      inflammation (P < 0.05). The relationship was also demonstrated by magnifying
      gastroscopy. Cardiac inflammation was linked to low acid output but not linked to
      the BA concentration or habitual smoking. Cardiac inflammation was more
      pronounced in patients without GERD. These results suggest that H. pylori is a
      major risk factor for cardiac inflammation in the Japanese.

PMID- 16602037
TI  - Treatment of musculoskeletal vascular anomalies.
AB  - The treatment of musculoskeletal vascular anomalies can be accomplished by means
      of challenging image-guided interventional techniques. Most patients benefit
      clinically from these procedures. Careful planning, appropriate training, and
      adequate patient care during and after the procedure are important to achieve
      optimal results and to minimize procedure-related risks.

PMID- 16602038
TI  - The damaging effect of ultrasound--to the examiner.

PMID- 16602039
TI  - Transrectal colour Doppler contrast sonography in the diagnosis of local
      recurrence after radical prostatectomy--comparison with MRI.
AB  - OBJECTIVE: To assess the usefulness of colour power-Doppler transrectal
      sonography before/after contrast agent in the detection of local recurrence in
      patients with rising prostate-specific antigen values after radical prostatectomy
      and to compare with magnetic resonance imaging . MATERIALS AND METHODS: 18
      patients with rising prostate-specific antigen values after prostatectomy
      underwent digital rectal examination, bone scintigraphy, magnetic resonance
      imaging, transrectal colour power-Doppler sonography before/after contrast agent,
      and transrectal sonography-guided biopsy. Sensitivity, specificity, accuracy,
      positive and negative predictive values were calculated. Results were correlated
      using McNemar binomial 2-tailed P-test. RESULTS: Baseline and contrast-enhanced
      transrectal colour power-Doppler sonography and contrast-enhanced magnetic
      resonance imaging identified recurrent disease in 6, 10 and 10 patients,
      respectively. Biopsy confirmed recurrence in 10 patients, but was positive also
      in 2 additional patients who were negative at contrast-enhanced transrectal
      colour power-Doppler sonography and contrast-enhanced magnetic resonance imaging.
      The remaining 6 patients were negative also at diagnostic imaging and biopsy
      after 30 days. Grey-scale transrectal sonography values were: sensitivity 91.7 %,
      specificity 66 %, PPV 91.6 %, NPV 40 %. Baseline colour power-Doppler transrectal
      sonography values were: sensitivity 38.5 %, specificity 85 %, diagnostic accuracy
      50 %, PPV 83.3 %, NPV 33.3 %. Contrast enhanced colour power-Doppler transrectal
      sonography and magnetic resonance imaging values were: sensitivity 76.9 %,
      specificity 100 %, diagnostic accuracy 83.3 %, PPV 100 %, NPV 62.5 %. CONCLUSION:
      Contrast-enhanced transrectal colour power-Doppler sonography increases
      specificity in the detection of local recurrence after prostatectomy. Magnetic
      resonance imaging yields equivalent accuracy. Biopsy remains the diagnostic gold
      standard, but the use of imaging methods may reduce the number of biopsies.

PMID- 16602040
TI  - [Intraoperative ultrasound in surgery of the parotid and the head-and-neck
      region].
AB  - Sonography of the head-and-neck region is well established in the preoperative
      diagnostic process of tumorous lesions. Its intraoperative use to localise small
      tumours, however, has been rarely investigated to date. We applied intraoperative
      ultrasound to 19 patients who underwent parotid surgery and evaluated the
      following criteria: intraoperative tumour presentation, scan quality, comparison
      between sonographic visualisation and tumour detection by palpation, histological
      tumour borders as well as postoperative complications. All lesions were
      reproduceable by intraoperative ultrasound and could be demonstrated in
      sufficient quality. None of the 19 parotid tumours could be identified by
      palpation pre- and intraoperatively. All tumour capsules remained intact, the
      tumours were completely removed and no postoperative complications were observed.
      Problems of ultrasound application may arise due to significantly altered
      anatomic landmarks while surgical preparation proceeds. Intraoperative ultrasound
      is fast, dynamic and feasible under sterile conditions. Especially in parotid
      surgery with small, non-palpable tumours, intraoperative ultrasound supports
      minimal-invasive surgery.

PMID- 16602041
TI  - [A conceptual analysis of the process of empowering the elderly at the community
      level].
AB  - The World Health Organization's 1986 Ottawa Declaration (WHO/Europe, 2005, April
      18) named the community as the best level at which to initiate health promotion
      activities and recognized "empowerment" as a main focus of modern health
      promotion activities. This implies that the success of health promotion
      initiatives relies on effective and creative community action, of which community
      empowerment is one of the three major influencing factors. Empowerment is a
      manner by which the resources of senior citizens can be reorganized and an
      awareness of their own capabilities cultivated. Moreover, empowerment is the best
      strategy to encourage senior citizen participation in the community as well as
      self-efficacy. Based on a review of the literature, this article introduces the
      definitions, concept development and vital components of community empowerment.
      Evidence-based research and examination instruments for the concept of
      empowerment are critically reviewed as well. In addition to discussing the
      application and effectiveness of senior citizen community participation and
      empowerment, this paper provides suggestions related to current community nursing
      care issues.

PMID- 16602042
TI  - [The application in public health nursing of the employee empowerment model and
      relevant considerations].
AB  - Empowerment, rooted in the black civil rights and other civic movements of the
      1960s, has greatly impacted thought and theories on health promotion activities,
      management strategies, and educational reform. Public health nurses are vital
      facilitators to the introduction and implementation of the empowerment concept in
      the health care field. Employee empowerment, based on the concept of empowerment,
      comprises the two domains of ability and power, which may be assessed through
      psychological and organizational empowerment. This article illustrates the
      employee empowerment model, the combination of cognitive empowerment model, and
      its application in public health nursing. The empowering process includes
      confirming feelings of powerlessness during the dialogue phase; empowerment
      education and organizational dialogue during the development phase; and
      collective action for goal-setting during the action phase. This paper also notes
      issues that should be considered related to model implementation, including new
      technology of old paradigm, the risk for more disempowered status, and an
      appropriate methodology for research paradigms. The employee empowerment model
      presented in this paper may be used as a guide to design empowerment education
      curricula for public health nurses.

PMID- 16602043
TI  - [Ideas of empowerment and their application: the example of vocational trainers
      in public hospitals].
AB  - Theories of empowerment differ in their assumptions about power, which can
      essentially be differentiated as either liberal, Marxist or post-structuralist.
      The liberal approach tends to intervene at the individual level while the Marxist
      and post-structuralist approaches do so at the systemic level. The case of
      vocational trainers in hospitals is adopted in this study as an example to
      illustrate the post-structuralist empowerment approach. The strategies of
      empowerment developed by these trainers include establishing peer support and
      dialectic relationships, transforming recognition about self-identity and
      organizational dynamics, developing action strategies, and connecting with other
      trainers for potential collective action.

PMID- 16602044
TI  - [The process of empowering community development: the experience of a community
      in Taipei city].
AB  - Community participation and development are the most difficult aspects of
      building healthy communities. They are also, however, the most essential parts of
      the process. It has been established that empowerment can ultimately enhance
      individual self-efficacy, influence organizational and social structures, and
      increase the sense of community and citizen's capabilities. This article
      demonstrates the experience of one community in Taipei City during a lengthy
      period of organization and development. It illustrates the different stages
      involved in community development and the functions of community health
      professionals. It seeks to provide insight into the importance of using
      empowerment in promoting communities' capabilities and the fact that only by
      developing organic communities that are rich in the energy of life can we develop
      sustainable communities.

PMID- 16602045
TI  - [Applying health beliefs to mothers who join in newborn hearing screening].
AB  - This study explores the potential of applying health belief models to studies of
      mothers who participate in newborn hearing screening (NHS) in order to establish
      a reference for the future research. The study was designed prospectively, with
      653 effective samples enrolled between November 1991 and April 1992 and data
      collected using a self-constructed questionnaire. The return rate for the
      questionnaire was 68.6%. Main conclusions include: (1) the decision to
      participate in newborn hearing screening correlates in a significant manner with
      potential participant backgrounds and actions clues; (2) "knowledge of NHS" and
      "perceived benefits of action in NHS" were the most important factors in this
      study associated with NHS participation; (3) subjects who participated in the NHS
      demonstrated significantly higher scores in "knowledge of NHS" and "perceived
      benefits of action in NHS" than those who did not participate. Significant
      negative correlation was identified between education level and perceived
      barriers to joining NHS. Significant positive correlation was observed between
      education level and NHS knowledge. Also, a significant positive relationship was
      identified between "perceived benefits of action in NHS" and both "clues of inner
      action" and "knowledge of NHS". However, "perceived barriers to NHS action" was
      found to share no significant relationship with any of the others. A positive
      relationship was also identified between "perceived benefits of action in NHS"
      and both "clues of outer action" and "amount of information resources"; and (4)
      "clues of outer action", "NHS knowledge", and "perceived benefits of NHS action"
      were found to be the most important indicators affecting study subjects' decision
      regarding whether or not to join NHS.

PMID- 16602046
TI  - [Reducing expenditure on infectious waste handling in the hemodialysis room].
AB  - Developing awareness of environmental protection issues and rising costs of
      medical treatment are causing all medical treatment centers to reduce expenditure
      on the processing of infectious hazardous wastes. This has become a major matter
      of policy in most hospitals. This project was undertaken because, in one unit,
      expenditure on infectious hazardous waste processing began to cost 50% of the
      hospital's entire monthly spending on such processing. A specialist team was
      established, which put into practice a monitoring plan and improvement measures.
      The results were as follows. First, with guidance, staff members realized the
      importance of reducing the quantity of infectious hazardous wastes. Second,
      infectious hazardous wastes were reduced by reducing the quantity, recycling, and
      not being wasteful. Third, following this effort, the hemodialysis room in
      question was able to save NT 2,786 dollars per month in expenditure on hygienic
      materials and waste handling fees of NT 5,597 dollars per month. A total of NT
      100,596 dollars was saved for the whole year. Fourth, the whole improvement
      project target completion rate was 240% and the progress rate was 13.3%.

PMID- 16602047
TI  - [Analysis phenomenology and application to nursing research].
AB  - Phenomenology has been divided into three schools of thought arising from
      different philosophical assumptions and methods. There is descriptive
      phenomenology, interpretative phenomenology, and a combination of both.
      Phenomenology has been adopted as a study method to explore experiences in
      different nursing fields in Taiwan. Husserlian descriptive phenomenology
      professes to utilize the skills of epoche, bracketing, and phenomenological
      reduction not only in order to seek the essence of phenomena, but also to allow
      the researcher to get into the participant's life-world to gain a deeper
      understanding of their experience; in other words, to let the true phenomenon or
      essence be revealed. By contrast, Heideggerian interpretative phenomenology
      rejected the idea that one can completely suspend one's presuppositions,
      prejudices or preconceived ideas by simply Being-in-the-world. One is immersed in
      and absorbing from the world, so one will not be able to notice everything that
      one is gaining from the world. Heidegger also insisted that any interpretation is
      only valid when background is taken into account. This not only facilitates the
      researcher's deeper understanding of the other's experience, but also facilitates
      more accurate interpretation of context and meaning. When researchers seek to
      follow Husserl's idea of performing bracketing in descriptive phenomenology, in
      order to truly put the concept into practice, they should understand their prior
      assumptions and maintain a written journal of reflections throughout the study.

PMID- 16602048
TI  - [The analysis and recommendation of the institutional respite care policy in
      Taiwan].
AB  - As the functionally impaired disabled elderly and the long-term care population
      has grown, concern about the physical, psychological and social demands facing
      primary caregivers has increased. An institutional respite care policy was
      adopted in Taiwan in 1998, but the rate of utilization of institutional care
      remains low. This article investigates the formative background, related
      circumstances and problems of respite care policy. The three dimensions of
      structure, process and outcome form the main framework for policy analysis.
      "Structure," includes demand and resources. "Process," includes health policy
      planning procedure, health administration and service delivery processes.
      "Outcome," covers service utilization, satisfaction, caregiver's well-being and
      care-receiver's institutionalization rate. In accordance with the results of the
      analysis the researchers propose recommendations about policy, practice,
      education and research, in the hope that these will be considered in relation to
      future modification and execution of respite care policy, in order to provide
      respite for suffering caregivers, and to carry out the ideal of aging in place.

PMID- 16602049
TI  - [Qualitative research: an introduction to focus group methodology and its
      application].
AB  - The focus group interview, an increasingly popular method in qualitative
      research, is used to obtain information that is highly accurate and relevant
      through a dynamic group interactive technique. Focus groups are used to gather
      ideas, opinions, perceptions, attitudes, and beliefs based on participants
      experiences in a defined area of interest. Focus groups can be used during the
      preliminary or exploratory stage of a study; during the course of a study (e.g.,
      to develop or evaluate a particular / interesting program of activities); or
      after a program has been completed (e.g., to assess impact or generate further
      avenues of research). Focus group interviews can be used either as a method in
      their own right or as a complement to other methods, especially to check
      triangulation and validity. While our study concluded that focus group interviews
      are an "easy and cost efficient" method to collect quality data, validity and
      relationship issues between focus group data and other data must be determined
      and considered in the results. This article introduces the background,
      definitions, focus group process, participants, interview guidelines, moderator
      responsibilities, and data collection and analysis related to the focus group
      methodology.

PMID- 16602050
TI  - [Nipple confusion and breastfeeding: a literature review].
AB  - Among the ten steps to successful breastfeeding advocated by the WHO and UNICEF,
      steps six and nine clearly state that formula supplementation and pacifier use,
      except when medically necessary, should be avoided. Early formula supplementation
      may not only interfere with the mother's lactation but also result in nipple
      confusion on the part of the baby. To avoid nipple confusion, the encouragement
      of cup feeding and the non-provision of pacifiers or bottles are required nursing
      practice in baby-friendly hospitals. However, the relationship between nipple
      confusion and the duration of breastfeeding has not been well examined. The
      purpose of this paper is to explore the relationships between three methods of
      feeding (i.e. pacifier, bottle feeding, and cup feeding), nipple confusion, and
      duration of breastfeeding. A hypothetical framework is proposed to explain these
      relationships on the basis of a review of the literature.

PMID- 16602051
TI  - [Using self-regulation theory to develop an intervention protocol for fluid
      control in patients undergoing hemodialysis].
AB  - With improvements in medical techniques, the survival rates among patients
      undergoing dialysis are gradually increasing. Poor fluid control leads to
      overweight and related complications. It is therefore important that new
      strategies be developed to encourage and maintain fluid control in patients
      receiving hemodialysis treatment. Self-regulation theory is a model that could be
      used to develop new strategies. On the basis of this theory, this article aims to
      design an intervention protocol for fluid control in hemodialysis patients.
      Examples are provided to describe how such a protocol might be applied to improve
      the fluid control. It is hoped that through behavioral modification of fluid
      control, patients undergoing hemodialysis will maintain the interdialytic weight
      gain and that cases of cardiovascular disease resulting from fluid overload will
      be reduced.

PMID- 16602052
TI  - [The nursing experience of a drug abuse patient complicated with rhabdomyolysis].
AB  - A lot of complications are caused by inappropriate use of drugs and one
      potentially fatal complication is rhabdomyolysis. This is a case study of the
      care of a patient with rhabdomyolysis induced by glue sniffing, during the period
      between August 7 and August 18, 2003. Roy's nursing assessment was applied as an
      index to evaluate the patient. By way of clinical observation, interview, and
      compilation of medical records, the nursing problems were established as
      ineffective breathing pattern, fluid volume deficit, and risks of violence and
      addiction. After a series of conversations, active attention, and professional
      nursing in emergency situations, the patient learned to control his behavior and
      accepted treatment. We hope that this complete nursing experience can in future
      serve as a reference in the management of patients with rhabdomyolysis.

PMID- 16602053
TI  - [The nursing experience of a primary caregiver providing care to a patient with
      moderate mental retardation].
AB  - This case report shares the researcher's experience and observations with regard
      to a primary caregiver responsible to provide nursing care to a patient suffering
      from moderate mental retardation during the time period October 1st, 2003 to July
      31st, 2004. The writer collected subjective and objective information using
      observation, face-to-face interviews, telephone interviews and scales, including
      the Caregiver Burden Scale and Taiwanese Depression Questionnaire. A holistic
      nursing assessment established that the primary nursing problem faced was
      caregiver anxiety. Through continuous caring and empathetic listening, the
      researcher encouraged the caregiver to describe her perceptions. Nursing
      intervention included providing information regarding professional patient care
      and encouraging support of the caregiver from the patient's family. Results
      demonstrated that, by the end of this study, the primary caregiver was better
      able to execute her duties and that her anxiety had been significantly relieved.

PMID- 16602054
TI  - [Management and improvement of the process of outpatient treatment of transient
      ischemic attacks in Neurology departments].
AB  - AIMS: To describe our experience in the ambulatory treatment of transient
      ischemic attacks (TIA) in a second-level hospital with the implementation of an
      example of process management within the different services involved in attending
      such conditions. PATIENTS AND METHODS: The following aspects of the process-
      mission, limits, flowchart, eligibility criteria and performance indicators
      (process, sentinel and effectiveness)--were defined by multidisciplinary
      consensus (Emergency, Vascular Surgery, Cardiology, Neurology and Radiology
      departments). This process was implemented from April 2002 to May 2004, and
      monthly assessments were carried out to check for problems and to introduce
      corrective measures. After ending the process, patients with TIA were admitted as
      inpatients for a hospital study. RESULTS: Definition of the process: medical care
      (diagnosis and treatment) of TIA patients who are eligible for a complete
      outpatient study within seven days. Patients evaluated: 254. Indicator 1
      (percentage of suitable referrals): 2002: 53%, 2003: 75%, 2004: 73%. Indicator 2
      (percentage of complete studies in less than one week): 2002: 35%, 2003: 57%,
      2004: 50%; hospitalised: 90%. Indicator 3 (infarcts during the study): 2002:
      4.3%, 2003: 0%, 2004: 0%; hospitalised: 0%. Indicator 4 (percentage of
      adjustments made to treatment): 2002: 39%, 2003: 31%, 2004: 62%; hospitalised:
      72%. Mean delay before visit: in February 2002: 90 days, in April 2002: 7.67 days
      and in April 2003: 5.37. Problems detected: delays in referrals, failure to fit
      hospitalisation criteria, delays in carrying out examinations not included in the
      protocol, unsuitable indicator design. Steps taken: redefinition of indicators,
      modification of the referral system, adjustments made to the circuits involved in
      carrying out tests, review of hospitalisation criteria. CONCLUSIONS: Process
      management is an ideal tool for achieving ongoing improvements in clinical
      praxis. Early monitoring makes it possible to detect problems and to implement
      corrective measures. In our area, the study of TIA must be performed in a
      hospital inpatient regimen in order to comply with the guidelines for clinical
      practice.

PMID- 16602055
TI  - [Differential effect of left and right temporal lobectomy on emotional
      recognition and experience in patients with epilepsy].
AB  - INTRODUCTION: Temporal lobe and amygdala are structures that participate in
      emotional processing. The purpose of this study was to determine the differential
      effect of left (LTL) and right (RTL) temporal lobectomy on emotional recognition
      and experience as well as mood in treatment resistant epileptics who were
      evaluated pre and post-surgically. PATIENTS AND METHODS: Five temporal lobe
      epileptic patients participated in the study (two from the right and three from
      the left hemisphere) who were evaluated before and after three months of the
      surgery. Emotional and prosodic recognition were evaluated, inside and outside of
      a social context, with and without time limit. Besides, subjective emotional
      experience while seeing movie fragments was evaluated as well as positive and
      negative emotional states, anxiety and depression. RESULTS: After the surgery,
      patients with RTL had lower number of correct responses in fear facial and
      prosodic recognition, while patients with LTL did not show deterioration or they
      even improved. There were not differences as a function of the intervened
      hemisphere neither in the intensity of emotions perceived in the scenes, nor in
      the emotional experience, however, both groups experienced a decrease of negative
      emotions and anxiety. CONCLUSIONS: The results suggest that RTL had a greater
      effect on emotional recognition outside of a context and with limited time than
      LTL, while in the emotional experience there were not differences between groups.
      Lobectomy induced an improvement on affective states.

PMID- 16602056
TI  - [The treatment of multiple sclerosis in Latin America: current practice and
      optimal standards. The findings of a survey among neurologists at an interactive
      workshop].
AB  - INTRODUCTION: Considerable progress has been made in the treatment of patients
      with relapsing-remitting multiple sclerosis (MS) over the last decade. Exactly
      how these changes are reflected in daily practice, however, is still not very
      well known. AIM: To hold interactive workshops so as to be able to evaluate the
      opinions of Latin-American neurologists about the therapeutic decisions taken
      with regard to MS. MATERIALS AND METHODS: By means of an interactive voting
      system, professionals attending each workshop replied to ten pre-established
      questions about when to start treatment, the use of magnetic resonance imaging
      (MRI) to supervise treatment, the definition of therapeutic failure and the role
      of treatment using immunosuppressants. The results were compared with those
      obtained in similar workshops attended by European and North American
      neurologists held six months earlier. RESULTS: The use of immunomodulators was
      considered to be useful in isolated demyelinating syndromes, as 40-50% endorsed
      their use in clinically stable patients. MRI was seen to be the most sensitive
      method of monitoring the effectiveness of the therapy -70.6% of them proposed the
      application of annual scans, which suggests a more frequent use in Latin America
      than in Europe or the USA. On defining therapeutic failure, the clinical criteria
      were more important than the MRI scan, and a switch from beta interferons to
      glatiramer acetate or vice versa was recommended. Treatment with
      immunosuppressants was considered to be useful in reducing the accumulated
      disability, but there was no agreement on how to use them. In Latin America,
      decisions about when to begin treatment seem to lie somewhere between the more
      favourable posture adopted in USA and the more conservative stance in Europe.
      CONCLUSIONS: This survey reflects the controversies that affect the therapeutic
      decisions concerning MS in Latin America and highlights the areas in which more
      data are needed to optimise the standards of treatment.

PMID- 16602057
TI  - [Acute disseminated encephalomyelitis due to hymenoptera stings].
AB  - INTRODUCTION: Hymenoptera stings can give rise to a variety of conditions. The
      most common is a self-limiting local allergic reaction, but occasionally they may
      produce potentially serious systemic reactions. Neurological complications are
      rare, but very varied and of differing degrees of severity. Some such
      consequences are those of a demyelinating nature, which can affect the central
      and/or peripheral nervous system. Their exact pathogenesis remains unknown but an
      autoimmune mechanism has been suggested. CASE REPORT: We report the case of a 28
      year-old female who had a clinical picture compatible with acute disseminated
      encephalomyelitis ten days after being stung several times by a bumblebee. The
      diagnosis was based on findings from magnetic resonance imaging and on the
      clinical-radiological course after a one-year follow-up. The patient was treated
      with massive doses of intravenous corticosteroids and immunoglobulins, which
      brought about partial recovery from the neurological deficit. CONCLUSIONS:
      Hymenoptera stings can produce demyelinating neurological complications,
      presumably related to the autoimmune system, which could benefit from treatment
      with immunomodulators such as corticosteroids, immunoglobulins or plasmapheresis.

PMID- 16602058
TI  - [Brain mechanisms involved in decision-making].
AB  - AIM: To review the studies on brain mechanisms in decision making within the
      framework of the somatic marker hypothesis, and based on experiments employing
      the Iowa Gambling Task. DEVELOPMENT: An overview of the somatic marker hypothesis
      is presented together with the review of the main results obtained from research
      in brain damaged patients, and normal subjects with functional neuroimaging
      studies, that have led to the identification of the neural structures involved in
      decision making in humans. CONCLUSIONS: The main region involved in decision
      making is the ventromedial prefrontal cortex, that integrates sensory, mnesic and
      emotional information relevant to the task. Other structures intervening in the
      various relevant processes in decision making are the amygdala (processing and
      encoding of the emotional signal and its association with contextual stimuli) and
      the cingulate cortex (process monitoring and response inhibition, especially in
      situations of uncertainty). The prefrontal dorsolateral cortex would also be
      involved through the necessary activation of the working memory in the decision
      making process, especially in the case of complex tasks.

PMID- 16602059
TI  - [Oxidative stress and Alzheimer's disease].
AB  - INTRODUCTION: According to the oxidative stress hypothesis, the pathogenesis of
      several diseases should be related with an excessive production of prooxidant
      substances (free radicals, transition metals), the deficiency of antioxidant
      defensive mechanisms, or both. Oxidative stress has been implicated in the
      pathogenesis of aging of the brain and several neurological diseases, including
      Alzheimer's disease (AD). DEVELOPMENT: In recent years there are many data
      suggesting a possible role of oxidative stress in the pathogenesis of AD. These
      include the demonstration of increased oxidation of lipids, proteins and
      deoxyribonucleic acid, alterations in mitochondrial function and the possible
      role of amyloid beta and its precursor protein in the oxidative reactions in
      experimental models (cortical neuronal cultures and transgenic animals).
      CONCLUSIONS: Many studies show increased oxidative stress in the brain of
      patients with AD, although its possible role con the pathogenesis of this disease
      are controversial.

PMID- 16602060
TI  - [Glutamate and Alzheimer's disease].
AB  - AIM: To analyze the importance of the neurotransmitter glutamate in the
      pathogenesis of Alzheimer's disease (AD). DEVELOPMENT: Elements of the
      physiological glutamatergic neurotransmission are reviewed, such as the neuronal
      types that utilize it, glutamatergic receptors and their characteristics, and
      glutamate transporters that remove this amino acid from the synaptic cleft. Some
      aspects of AD neuropathology changes in the brain content of glutamate, and other
      changes in the different types of glutamatergic receptors and transporters are
      also examined. A mechanism of disease related to prolonged exposure to glutamate,
      known as 'slow or indirect excitotoxicity', peculiar to some neurodegenerative
      diseases, is analyzed, as are the causes that may unleash it in AD. Some of the
      neuropathologic findings in this disease may be related to the glutamatergic
      dysfunction. CONCLUSION: Glutamatergic dysfunction plays an important role in the
      pathogenesis of this illness, although this disturbance is probably a secondary
      phenomenon to other neurochemical, genetic or metabolic changes, essential to the
      development of AD.

PMID- 16602061
TI  - [Inflammation and Alzheimer's disease].
AB  - INTRODUCTION: Although Alzheimer's disease (AD) has not been traditionally
      regarded as an inflammatory process, there is an innate chronic inflammatory
      reaction in the affected tissues. The most important elements of this reaction
      are the activation of the phagocytic cells (microglia) with the production of
      cytokines and toxic substances, and the activation of the complement system.
      DEVELOPMENT: Inflammation is considered an important, although secondary, element
      in the pathogenesis of AD. It has been observed in epidemiological studies and in
      laboratory that treatment with anti-inflammatory drugs delays the appearance of
      AD. There are still no studies in humans that recommend the use of these drugs on
      a generalized way. CONCLUSIONS: The therapeutic targets given by the study of the
      inflammatory system in the brain are under investigation to obtain new drugs with
      less adverse effects. Those drugs could be used as primary and secondary
      prevention of AD.

PMID- 16602062
TI  - [Brain, mind and symptoms].
AB  - INTRODUCTION: Neuropsychiatry, which is the point where neurology and psychiatry
      meet, together with other neighbouring disciplines (psychology, anthropology,
      neurochemistry, neurophysiology, and so forth), are committed to unravelling both
      the psychopathological definition and the anatomical-physiological foundations of
      mental symptoms (signs). DEVELOPMENT: This work attempts to review several
      moments in the history of the localisation of neurology and the difficulties
      involved in accomplishing a systematisation of mental symptoms. CONCLUSIONS:
      Further knowledge of this delicate matter--the mind, or more specifically, the
      sick brain-mind complex--can only be gained by cooperation in a number of
      different areas (clinical, psychological, philosophical, biochemical, imaging,
      and so forth).

PMID- 16602063
TI  - [Sciatica due to muscular hydatidosis].

PMID- 16602064
TI  - [Low serum free thyroxine concentration in a patient treated with oxcarbazepine].

PMID- 16602065
TI  - [Tooth-brushing-induced epilepsy].

PMID- 16602067
TI  - [Other factors that condition the long-term toxicity of 3,4
      methylenedioxymethamphetamine ('ecstasy')].

PMID- 16602068
TI  - Microscopy reveals disease control through novel effects on fungal development: a
      case study with an early-generation benzophenone fungicide.
AB  - The benzophenones are a new class of agricultural fungicides that demonstrate
      protectant, curative and eradicative/antisporulant activity against powdery
      mildews. The chemistry is represented in the marketplace by the fungicide
      metrafenone, recently introduced by BASF and discussed in the following paper.
      The benzophenones show no evidence of acting by previously identified biochemical
      mechanisms, nor do they show cross-resistance with existing fungicides. The value
      of microscopy in elucidating fungicide mode of action is demonstrated through
      identification of the effects of an early benzophenone, eBZO, on mildew
      development. eBZO caused profound alterations in the morphology of powdery
      mildews of both monocotyledons and dicotyledons, affecting multiple stages of
      fungal development, including spore germination, appressorial formation,
      penetration, surface hyphal morphology and sporogenesis. Identification of
      analogous effects of eBZO on sporulation in the model organism Aspergillus
      nidulans (Eidam) Winter provides a unique opportunity to elucidate important
      morphogenetic regulatory sites in the economically important obligate pathogens,
      the powdery mildews. Benzophenones provide a further example of the benefits of
      whole-organism testing in the search for novel fungicide modes of action.

PMID- 16602069
TI  - Further steps toward direct magnetic resonance (MR) imaging detection of neural
      action currents: optimization of MR sensitivity to transient and weak currents in
      a conductor.
AB  - The characteristics of an MRI technique that could be used for direct detection
      of neuronal activity are investigated. It was shown that magnitude imaging using
      echo planar imaging can detect transient local currents. The sensitivity of this
      method was thoroughly investigated. A partial k-space EPI acquisition with
      homodyne reconstruction was found to increase the signal change. A unique
      sensitivity to the position of the current pulse within the imaging sequence was
      demonstrated with the greatest signal change occurring when the current pulse
      coincides with the acquisition of the center lines of k-space. The signal change
      was shown to be highly sensitive to the spatial position of the current conductor
      relative to the voxel. Furthermore, with the use of optimization of spatial and
      temporal placement of the current pulse, the level of signal change obtained at
      this lower limit of current detectability was considerably magnified. It was
      possible to detect a current of 1.7 microA applied for 20 ms with an imaging time
      of 1.8 min. The level of sensitivity observed in our study brings us closer to
      that theoretically required for the detection of action currents in nerves.

PMID- 16602070
TI  - Manganese-enhanced magnetic resonance imaging for in vivo assessment of damage
      and functional improvement following spinal cord injury in mice.
AB  - In past decades, much effort has been invested in developing therapies for spinal
      injuries. Lack of standardization of clinical read-out measures, however, makes
      direct comparison of experimental therapies difficult. Damage and therapeutic
      effects in vivo are routinely evaluated using rather subjective behavioral tests.
      Here we show that manganese-enhanced magnetic resonance imaging (MEMRI) can be
      used to examine the extent of damage following spinal cord injury (SCI) in mice
      in vivo. Injection of MnCl2 solution into the cerebrospinal fluid leads to
      manganese uptake into the spinal cord. Furthermore, after injury MEMRI-derived
      quantitative measures correlate closely with clinical locomotor scores. Improved
      locomotion due to treating the detrimental effects of SCI with an established
      therapy (neutralization of CD95Ligand) is reflected in an increase of manganese
      uptake into the injured spinal cord. Therefore, we demonstrate that MEMRI is a
      sensitive and objective tool for in vivo visualization and quantification of
      damage and functional improvement after SCI. Thus, MEMRI can serve as a
      reproducible surrogate measure of the clinical status of the spinal cord in mice,
      potentially becoming a standard approach for evaluating experimental therapies.

PMID- 16602071
TI  - Metrafenone: studies on the mode of action of a novel cereal powdery mildew
      fungicide.
AB  - Powdery mildew fungi are among the major pathogens causing diseases of cereals in
      the world. The mode of action of a novel systemic benzophenone fungicide,
      metrafenone, which is based on a precursor that is discussed in the preceding
      paper, has been analysed on the powdery mildew fungi of barley (Blumeria graminis
      Speer f. sp. hordei Marchal) and wheat (Blumeria graminis Speer f. sp. tritici
      Marchal). Preventive treatments reduced germination and blocked development
      beyond formation of appressoria, which penetrated less often. Moreover,
      metrafenone turned out to be an efficient curative fungicide, which rapidly
      affected fungal survival at low concentrations. The fungicide induced swelling,
      bursting and collapse of hyphal tips, resulting in the release of globules of
      cytoplasm. Bifurcation of hyphal tips, secondary appressoria and hyperbranching
      were also frequently observed. A histochemical analysis showed that metrafenone
      caused disruption of the apical actin cap and apical vesicle transport as well as
      weakening of the cell wall at hyphal tips. Finally, metrafenone strongly reduced
      sporulation. Reduced sporulation was associated with malformation of
      conidiophores that showed irregular septation, multinucleate cells and
      delocalisation of actin. Microtubules appeared to be only secondarily affected in
      metrafenone-treated B. graminis. The results suggest that the mode of action of
      metrafenone interferes with hyphal morphogenesis, polarised hyphal growth and the
      establishment and maintenance of cell polarity. Metrafenone likely disturbs a
      pathway regulating organisation of the actin cytoskeleton.

PMID- 16602072
TI  - Appraisals and coping in people living with cancer: a meta-analysis.
AB  - The present meta-analysis examined the relationship between primary appraisal
      dimensions and coping strategies in people with cancer. Primary appraisals were
      operationalized as appraisals of threat, challenge, and harm/loss. Coping was
      operationalized according to two coping taxonomies: the first based on coping
      efforts to manage the stressor itself and/or the distressful feelings associated
      with it (problem- or emotion-focused coping, respectively) and the second based
      on the general orientation of the coping efforts (approach or avoidance coping).
      Appraisals of threat were (counter-intuitively) related to use of problem-focused
      coping (r=0.20); appraisals of harm and/or loss were related to avoidance coping
      (r=0.23); and appraisals of challenge were related to both problem-focused
      (r=0.15) and approach coping (r=0.14). These findings suggest that individuals
      with cancer who appraise their illness as a threat are likely to use more problem
      focused coping strategies. Individuals who appraise their cancer as a harm/loss,
      however, are likely to use more avoidance coping strategies. And finally, those
      who appraise their cancer as a challenge are likely to use approach coping
      strategies. Factors found to moderate the relationship between appraisals and
      coping included age of the participant, time since diagnosis, and type of cancer.

PMID- 16602073
TI  - Quantitative lung perfusion mapping at 0.2 T using FAIR True-FISP MRI.
AB  - Perfusion measurements in lung tissue using arterial spin labeling (ASL)
      techniques are hampered by strong microscopic field gradients induced by
      susceptibility differences between the alveolar air and the lung parenchyma. A
      true fast imaging with steady precession (True-FISP) sequence was adapted for
      applications in flow-sensitive alternating inversion recovery (FAIR) lung
      perfusion imaging at 0.2 Tesla and 1.5 Tesla. Conditions of microscopic static
      field distribution were assessed in four healthy volunteers at both field
      strengths using multiecho gradient-echo sequences. The full width at half maximum
      (FWHM) values of the frequency distribution for 180-277 Hz at 1.5 Tesla were more
      than threefold higher compared to 39-109 Hz at 0.2 Tesla. The influence of
      microscopic field inhomogeneities on the True-FISP signal yield was simulated
      numerically. Conditions allowed for the development of a FAIR True-FISP sequence
      for lung perfusion measurement at 0.2 Tesla, whereas at 1.5 Tesla microscopic
      field inhomogeneities appeared too distinct. Perfusion measurements of lung
      tissue were performed on eight healthy volunteers and two patients at 0.2 Tesla
      using the optimized FAIR True-FISP sequence. The average perfusion rates in
      peripheral lung regions in transverse, sagittal, and coronal slices of the
      left/right lung were 418/400, 398/416, and 370/368 ml/100 g/min, respectively.
      This work suggests that FAIR True-FISP sequences can be considered appropriate
      for noninvasive lung perfusion examinations at low field strength.

PMID- 16602074
TI  - Estimating treatment effects in randomized trials with treatment switching.

PMID- 16602075
TI  - Evaluation of stereo-array isotope labeling (SAIL) patterns for automated
      structural analysis of proteins with CYANA.
AB  - Recently we have developed the stereo-array isotope labeling (SAIL) technique to
      overcome the conventional molecular size limitation in NMR protein structure
      determination by employing complete stereo- and regiospecific patterns of stable
      isotopes. SAIL sharpens signals and simplifies spectra without the loss of
      requisite structural information, thus making large classes of proteins newly
      accessible to detailed solution structure determination. The automated structure
      calculation program CYANA can efficiently analyze SAIL-NOESY spectra and
      calculate structures without manual analysis. Nevertheless, the original SAIL
      method might not be capable of determining the structures of proteins larger than
      50 kDa or membrane proteins, for which the spectra are characterized by many
      broadened and overlapped peaks. Here we have carried out simulations of new SAIL
      patterns optimized for minimal relaxation and overlap, to evaluate the combined
      use of SAIL and CYANA for solving the structures of larger proteins and membrane
      proteins. The modified approach reduces the number of peaks to nearly half of
      that observed with uniform labeling, while still yielding well-defined structures
      and is expected to enable NMR structure determinations of these challenging
      systems.

PMID- 16602076
TI  - Density-functional computation of 53Cr NMR chemical shifts.
AB  - 53Cr chemical shifts of CrO4(2-), Cr2O7(2-), CrO3X-, CrO2X2(X = F, Cl), and
      Cr(CO)5L (L = CO, PF3, CHNH2, CMeNMe2) are computed, using geometries optimized
      with the gradient-corrected BP86 density functional, at the gauge-including
      atomic orbitals (GIAO)-, BPW91-, and B3LYP levels. For this set of compounds,
      substituent effects on delta(53Cr) are better described with the pure BPW91
      functional than with B3LYP, in contrast to most other transition-metal chemical
      shifts studied so far. For selected cases, 53Cr NMR line widths can be
      rationalized in terms of electric field gradients (EFGs) computed with the BPW91
      functional, but in general other factors such as molecular correlation times
      appear to be dominating. 53Cr chemical shifts and EFGs are predicted for CrO3,
      Cr(C6H6)2, Cr(C6H6)CO3, and, with reduced reliability, for Cr2(mu2-O2CH)4.

PMID- 16602077
TI  - A new oleanane glycoside from the roots of Astragalus caprinus.
AB  - A novel oleanane-type triterpene saponin (1) together with two known molecules,
      soyasapogenol B and astragaloside VIII were isolated from the roots of Astragalus
      caprinus. Their structural elucidation was performed mainly by 2D NMR techniques
      (COSY, TOCSY, NOESY, HSQC, HMBC) and mass spectrometry. Compound 1 was determined
      as 3-O-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucuronopyranosyl]-22-O-beta-D
      apiofuranosyl-soyasapogenol B.

PMID- 16602078
TI  - 29Si-13C spin-spin couplings over Si-O-Carom link.
AB  - 29Si-13C couplings were measured in para substituted silylated phenols, X--C6H4-
      O--SiR1R2R3 (X = NO2, CF3, Cl, F, H, CH3, CH3O). The SiR1R2R3 silyl groups
      included trimethylsilyl (Si(CH3)3, TMS), tert-butyldimethylsilyl
      (Si(CH3)2C(CH3)3, TBDMS), dimethylsilyl (SiH(CH3)2, DMS), and tert-
      butyldiphenylsilyl (Si(C6H5)2C(CH3)3, TBDPS). Previously developed (Si,C,Si)gHMQC
      methods and narrow 29Si lines allowed the determination of coupling constants
      over up to five bonds. Besides the number of intervening bonds between the
      silicon and carbon atoms, all the measurable couplings depend also on the nature
      of the substituents on the silicon. The two- and three-bond couplings are not
      affected by ring substitution in the para position. These properties render the
      29Si-13C couplings suitable for line assignment in the spectra of silylated
      polyphenols. The experimental results are in reasonable agreement with
      theoretical calculations. The calculations show, in agreement with the data
      reported in the literature for couplings between other nuclei, that the two-bond
      and three-bond couplings, which are of similar magnitudes, are of opposite signs.
      If the signs of these geminal and vicinal couplings could be determined
      experimentally, they would greatly facilitate the line assignment. The four- and
      five-bond couplings are affected by the substituent X in a nontrivial manner.

PMID- 16602079
TI  - Synthesis and herbicidal activity of novel alpha,alpha,alpha-trifluoro-m-tolyl
      pyridazinone derivatives.
AB  - A series of novel alpha,alpha,alpha-trifluoro-m-tolyl pyridazinone derivatives
      was synthesised. Herbicidal activities of the two intermediate compounds and 15
      pyridazinone derivatives were evaluated through barnyardgrass and rape cup tests
      and Spirodela polyrrhiza (L.) Schleiden tests. Selected compounds were also
      evaluated under greenhouse conditions. Bleaching activities were observed at 10
      microg ml(-1) and some compounds exhibited herbicidal activities at a rate of 300
      g ha(-1). The relationship between crystal structures and herbicidal activities
      is discussed through a comparison of two compounds (5a and 5f).

PMID- 16602080
TI  - Structure elucidation of a new friedelane triterpene from the mangrove plant
      Hibiscus tiliaceus.
AB  - From the stem and bark of the mangrove plant Hibiscus tiliaceus, a new friedelane
      type triterpene named 27-oic-3-oxo-28-friedelanoic acid (1) together with eight
      known triterpenoids involving five friedelane-type derivatives was isolated. The
      structure of 1 was determined by extensive 2D NMR (DQF-COSY, HMQC, HMBC, and
      NOESY) data analyses. All the compounds were obtained from mangrove plants for
      the first time.

PMID- 16602081
TI  - Correction of systematic errors in CORE processing of DOSY data.
AB  - DOSY data for mixtures are commonly processed either by single channel methods
      (e.g. HR-DOSY) or multichannel methods (e.g. CORE). Both aim to separate the
      signals from species of different molecular sizes by their diffusion
      coefficients; the result is displayed either as a 2D plot (as in HR-DOSY) or as
      individual spectra (as in CORE). Both types of methods are sensitive to any
      systematic errors in the experimental data. The effects of, and remedies for, two
      such sources of error, spatially non-uniform pulsed field gradients (PFGs) and
      instrument instability, are demonstrated for CORE processing, using a corrected
      form of the Stejskal-Tanner equation and reference deconvolution, respectively.

PMID- 16602082
TI  - Solvent effect in 1H NMR spectra of 3'-hydroxy-4'-methoxy isoflavonoids from
      Astragalus membranaceus var. mongholicus.
AB  - Four 3'-hydroxy-4'-methoxy-isoflavonoids: calycosin-7-O-beta-D-glucopyranoside
      (1), calycosin (2), pratensein-7-O-beta-D-glucopyranoside (3), and pratensein (4)
      were isolated from Astragalus membranaceus var. mongholicus, among which compound
      4 was obtained from this plant for the first time. The solvent effect obscuring
      (1)H signal patterns of B ring of compounds 1-4 was reported to avoid mis
      assignments. Previously reported NMR data of compounds 1 and 2 were corrected
      based on 1D and 2D NMR experiments.

PMID- 16602083
TI  - The effects of kaolin particle film on Plutella xylostella behaviour and
      development.
AB  - Studies were conducted to evaluate the effect of a kaolin-based particle film
      against the diamondback moth, Plutella xylostella (L.) (Lepidoptera:
      Plutellidae). The effect of the particle film on development, survival and host
      plant selection was tested on calabrese seedlings, Brassica oleracea italica
      Plenck cv. Fiesta F(1), under controlled environmental conditions in the
      laboratory. Survival to adulthood was significantly reduced and development time
      increased on kaolin-treated compared with water-treated host plants. The hatch
      rate of neonate P. xylostella larvae from eggs laid on an artificial substrate
      was unaffected by the particle film applied after oviposition. Experiments showed
      that, when given the choice, significantly fewer larvae first made contact with
      the kaolin-treated compared with the water-treated plant material and that after
      24 h there were still significantly fewer larvae present on kaolin-treated
      leaves. Adult females, however, deposited more eggs on host plants coated with
      the kaolin particle film. As part of this series of experiments the water control
      treatment was compared with plant material which had been sprayed with kaolin on
      the upper surface only and on both leaf surfaces. In general, any observed
      treatment effect was enhanced with an increase in the particle film coverage. The
      results warrant the extension of investigations of kaolin-based particle films to
      field-based P. xylostella management strategies.

PMID- 16602084
TI  - Acaricidal activities of paeonol and benzoic acid from Paeonia suffruticosa root
      bark and monoterpenoids against Tyrophagus putrescentiae (Acari: Acaridae).
AB  - The acaricidal activities of paeonol (2'-hydroxy-4'-methoxyacetophenone) and
      benzoic acid identified in the root bark of tree peony, Paeonia suffruticosa
      Andrews, against copra mite, Tyrophagus putrescentiae (Schrank), adults were
      examined using direct contact and vapour phase toxicity bioassays and compared
      with those of cinnamyl acetate, cinnamyl alcohol and 37 monoterpenoids as well as
      the acaricides benzyl benzoate, dibutyl phthalate and N,N-diethyl-m-toluamide
      (DEET). Based on LD(50) values in fabric piece contact toxicity bioassays, the
      acaricidal activities of benzoic acid (4.80 microg cm(-2)) and paeonol (5.29
      microg cm(-2)) were comparable to that of benzyl benzoate (4.46 microg cm(-2))
      but more pronounced than those of DEET (30.03 microg cm(-2)) and dibutyl
      phthalate (25.23 microg cm(-2)). In vapour phase toxicity bioassays, paeonol and
      benzoic acid were much more effective in closed containers than in open ones,
      indicating that the effects of these compounds were largely due to action in the
      vapour phase. As judged by 24 h LD(50) values, (1S)-(-)-verbenone (7.42 mg per
      disc) was the most toxic fumigant, followed by (1S)-(-)-camphor, (S)-(+)-carvone,
      (R)-(-)-linalool and (+/-)-camphor (10.45-18.18 mg). Potent fumigant toxicity was
      also observed with paeonol, (2S,5R)-(-)-menthone, (+/-)-citronellal, benzoic
      acid, (1S,4R)-(-)-alpha-thujone and (R)-(+)-pulegone (25.10-34.63 mg). Neither
      benzyl benzoate, DEET nor dibutyl phthalate caused fumigant toxicity. Paeonia
      root bark-derived materials, particularly paeonol and benzoic acid, as well as
      the monoterpenoids described, merit further study as potential acaricides or as
      leads for the control of T. putrescentiae.

PMID- 16602085
TI  - A study on the molecular mechanism of resistance to amicarthiazol in Xanthomonas
      campestris pv. citri.
AB  - Three amicarthiazol-resistant mutants (Xuv10, Xuv20 and Xuv40) were obtained by
      UV induction and used in this study. Minimal inhibition concentrations (MICs) of
      amicarthiazol against the growth of mutants and wild-type isolate were 400 and
      100 microg ml(-1) respectively. Inhibition by amicarthiazol of succinate
      dehydrogenase (SDH) activities of Xanthomonas campestris pv. citri (Hasse) Dye
      wild-type isolate (Xcc) and three resistant mutants derived from this isolate
      were assayed using triphenyltetrazolium chloride (TTC). The SDH activities of
      these mutants were significantly lower than that of Xcc. The complete nucleotide
      sequences of four subunits (SdhA, SdhB, SdhC and SdhD) of succinate-ubiquinone
      oxidoreductase (SQR) were cloned by polymerase chain reaction (PCR)
      amplification. An amino acid mutation (His229--> Leu229) in sdhB was found to
      confer resistance of X. campestris pv. citri to amicarthiazol. It is suggested
      that this mutation alters the SDH complex in some way that prevents binding of
      amicarthiazol.

PMID- 16602086
TI  - Persistence and efficacy of two diatomaceous earth formulations and a mixture of
      diatomaceous earth with natural pyrethrum against Tribolium confusum Jacquelin du
      Val (Coleoptera: Tenebrionidae) on wheat and maize.
AB  - Laboratory tests were conducted to assess the insecticidal and residual effects
      of three diatomaceous earth (DE) formulations, Insecto, PyriSec and SilicoSec,
      against Tribolium confusum Jacquelin du Val on wheat and maize. Quantities of
      wheat and maize were treated with the above formulations at 500, 1000 and 1500 mg
      kg(-1) and stored at 25 degrees C and 55% relative humidity (RH). Samples were
      taken on the day of storage and every 30 days until completion of a 360 day
      period of storage. Adults of T. confusum were exposed to these samples at 25
      degrees C and 55% RH and the mortality was measured after 24 and 48 h and 7 and
      14 days of exposure. Adult mortality was higher on wheat than on maize. At the
      beginning of the storage period, mortalities after 14 day exposure on maize
      treated with the highest rate were 60, 63 and 81% for Insecto, PyriSec and
      SilicoSec respectively, while on wheat the mortality was 100% for all DEs. On the
      same commodities 360 days after treatment the respective mortality figures for
      wheat were 99, 98 and 100%, while in the case of maize they did not exceed 7%.
      Generally, mortality at exposures < or =48 h decreased with increasing storage
      time. Furthermore, although mortality on wheat increased with dose, the increase
      in DE dose from 1000 to 1500 mg kg(-1) resulted in only a small increase in
      mortality. Thus a DE treatment of 1000 mg kg(-1) was shown to provide long-term
      protection of wheat against T. confusum, although higher DE application rates and
      exposure intervals are needed for a satisfactory level of protection of maize
      against this pest.

PMID- 16602088
TI  - Covalent modification of porous implants using extracellular matrix proteins to
      accelerate neovascularization.
AB  - Healing associated with many polymeric biomedical implants commonly involves the
      formation of an avascular fibrous capsule. The lack of either formation or
      persistence of blood vessels in formed fibrous capsules, as well as a lack of new
      blood vessels within porous polymeric implants, often results in poor performance
      of the implant. The current study evaluated the use of extracellular matrix
      protein modification of a commonly used biomedical implant material, expanded
      polytetrafluoroethylene (ePTFE), as a mechanism to increase the
      neovascularization both within these porous implants and in tissue that forms in
      the peri-implant area. Discs of ePTFE were covalently modified with different
      extracellular matrix proteins including collagen type IV, fibronectin, and
      laminin type I. Discs were implanted into the adipose tissue of adult rats, and
      following a 5-week implant phase, histologic analysis of peri-implant tissue
      angiogenesis and implant neovascularization was performed. Striking differences
      were observed in angiogenic and neovascularization responses to matrix-modified
      ePTFE when compared with control, untreated ePTFE. Fibronectin treatment resulted
      in an extensive inflammatory response but, relative to the degree of
      inflammation, limited evidence of tissue angiogenesis or polymer
      neovascularization. Collagen type IV treatment groups exhibited a significant
      increase in angiogenesis in the peri-implant tissue with minimal evidence of
      implant neovascularization. In contrast to all other implant modifications,
      laminin type 1-treated ePTFE samples stimulated an extensive peri-implant tissue
      angiogenic response and a coordinate neovascularization of the porous interstices
      of the biomaterial.

PMID- 16602089
TI  - Significantly accelerated osteoblast cell growth on aligned TiO2 nanotubes.
AB  - Vertically aligned yet laterally spaced nanoscale TiO2 nanotubes have been grown
      on Ti by anodization, and the growth of MC3T3-E1 osteoblast cells on such
      nanotubes has been investigated. The adhesion/propagation of the osteoblast is
      substantially improved by the topography of the TiO2 nanotubes with the filopodia
      of growing cells actually going into the nanotube pores, producing an interlocked
      cell structure. The presence of the nanotube structure induced a significant
      acceleration in the growth rate of osteoblast cells by as much as approximately
      300-400%.

PMID- 16602090
TI  - Cytokine release of mononuclear leukocytes (PBMC) after contact to a carbonated
      calcium phosphate bone cement.
AB  - Human leukocytes (peripheral blood mononuclear cells, PBMC) were overlaid on
      calcium phosphate bone cement (CBC, Norian SRS) and allowed to settle for 1 h
      under cell culture conditions. Subsequently, the cells were either left
      unstimulated (i.e. sham stimulation using cell culture medium), or stimulated
      with toxic shock syndrome toxin-1 (TSST-1, 10 ng/mL), staphylococcal enterotoxin
      B (SEB, 10 ng/mL), or concanavalin A (ConA, 2 microg/mL) for further 24 h using
      cell culture conditions. Supernatants were then analyzed for cytokine content
      (interleukin-1 receptor antagonist, IL-1ra; IL-2; IL-6; IL-10; IL-12) by enzyme
      linked immunosorbent assay. While the spontaneous generation of cytokines was not
      influenced, the IL-2 release from stimulated PBMC was significantly decreased in
      contrast to other analyzed cytokines after contact to the curing CBC compared to
      control incubations without CBC. This decrease in IL-2 release was not due to
      known inhibitors of IL-2 synthesis platelet factor-4 (PF-4), IL-10, TGF-beta, or
      elevated calcium ion concentrations.

PMID- 16602091
TI  - The history of sweet taste: not exactly a piece of cake.
AB  - Understanding the molecular bases of sweet taste is of crucial importance not
      only in biotechnology but also for its medical implications, since an increasing
      number of people is affected by food-related diseases like, diabetes,
      hyperlipemia, caries, that are more or less directly linked to the secondary
      effects of sugar intake. Despite the interest paid to the field, it is only
      through the recent identification and functional expression of the receptor for
      sweet taste that new perspectives have been opened, drastically changing our
      approach to the development of new sweeteners. We shall give an overview of the
      field starting from the early days up to discussing the newest developments.
      After a review of early models of the active site, the mechanisms of interaction
      of small and macromolecular sweet molecules will be examined in the light of
      accurate modeling of the sweet taste receptor. The analysis of the homology
      models of all possible dimers allowed by combinations of the human T1R2 and T1R3
      sequences of the sweet receptor and the closed (A) and open (B) conformations of
      the mGluR1 glutamate receptor shows that only 'type B' sites, either T1R2(B) and
      T1R3(B), can host the majority of small molecular weight sweeteners. Simultaneous
      binding to the A and B sites is not possible with two large sweeteners but is
      possible with a small molecule in site A and a large one in site B. This
      observation accounted for the first time for the peculiar phenomenon of synergy
      between some sweeteners. In addition to these two sites, the models showed an
      external binding site that can host sweet proteins.

PMID- 16602092
TI  - Methylmalonic and propionic aciduria.
AB  - Methylmalonic and propionic aciduria (PA) are the most frequent forms of branched
      chain organic acidurias. These autosomal recessive disorders result from
      deficient activity of methylmalonyl-CoA mutase and propionyl-CoA carboxylase,
      respectively. Clinically, acute or chronic neurologic signs are caused by the
      accumulation of toxic compounds proximal to the metabolic block. Phenotype varies
      from severe neonatal-onset forms with high mortality and poor outcome to milder
      forms with a later onset. In both cases the clinical course is dominated by the
      risk of relapses of life-threatening episodes of metabolic decompensation and of
      severe organ failure. Despite improvement of treatment, the overall outcome
      remains disappointing with no major differences between the two diseases. The
      diagnosis is based on the presence of characteristic compounds in body fluids as
      detected by organic acid analysis in urine and acylcarnitine profile in blood.
      Therapy is based on low-protein high-energy diet, carnitine supplementation, and
      metronidazole. Some patients with methylmalonic aciduria (MMA) respond to
      pharmacological doses of vitamin B12. Given the poor long-term prognosis, liver
      transplantation has been recently attempted as an alternative therapy to
      conventional medical treatment to cure the underlying metabolic defect.
      Nevertheless, the overall experience to date does not clearly demonstrate its
      effectiveness in preventing further deterioration or improving survival and
      quality of life. The recent implementation of neonatal screening by electrospray
      tandem mass spectrometry has decreased early mortality and improved the short
      term outcome, without changing the detection rate of both diseases in the
      screening population compared to clinically detected cases. However, the limited
      number of patients and the short duration of their follow-up do not yet permit
      drawing final conclusions on its effect on the long-term outcome of methylmalonic
      and propionic acidemia.

PMID- 16602095
TI  - The genetic tyrosinemias.
AB  - The genetic tyrosinemias are characterized by the accumulation of tyrosine in
      body fluids and tissues. The most severe form of tyrosinemia, Type I, is a
      devastating disorder of childhood that causes liver failure, painful neurologic
      crises, rickets, and hepatocarcinoma. This disorder is caused by a deficiency of
      fumarylacetoacetate hydrolase (FAH). If untreated, death typically occurs at less
      than 2 years of age, with some chronic forms allowing longer survival. It has a
      prevalence of about 1 in 100,000 newborns in the general population.
      Oculocutaneous tyrosinemia, Type II, is caused by a deficiency of tyrosine
      aminotransferase (TAT). It clinically presents with hyperkeratotic plaques on the
      hands and soles of the feet and photophobia due to deposition of tyrosine
      crystals within the cornea. Tyrosinemia Type III is an extremely rare disorder
      caused by a deficiency of 4-hydroxyphenylpyruvic dioxygenase. It has been
      associated with ataxia and mild mental retardation. These disorders are diagnosed
      by observing elevated tyrosine by plasma amino acid chromatography and
      characteristic tyrosine metabolites by urine organic acid analysis. In
      tyrosinemia Type I, methionine is also elevated, reflecting impaired
      hepatocellular function. Urine organic acids show elevated p-hydroxy-phenyl
      organic acids in each type of tyrosinemia, and the pathognomic succinylacetone in
      tyrosinemia Type I. Diagnosis can be confirmed by enzyme or molecular studies in
      tyrosinemia Type I. Therapy consists of a diet low in phenylalanine and tyrosine
      for each of the tyrosinemias and 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3
      cyclohexanedione (NTBC) for tyrosinemia Type I.

PMID- 16602094
TI  - Clinical, biochemical, and molecular spectrum of hyperargininemia due to arginase
      I deficiency.
AB  - The urea cycle consists of six consecutive enzymatic reactions that convert waste
      nitrogen into urea. Urea cycle disorders are a group of inborn errors of hepatic
      metabolism that often result in life threatening hyperammonemia and
      hyperglutaminemia. Deficiencies of all of the enzymes of the cycle have been
      described and although each specific disorder results in the accumulation of
      different precursors, hyperammonemia and hyperglutaminemia are common biochemical
      hallmarks of these disorders. Arginase is the enzyme involved in the last step of
      the urea cycle. It catalyzes the conversion of arginine to urea and ornithine.
      The latter reenters the mitochondrion to continue the cycle. Hyperargininemia is
      an autosomal recessive disorder caused by a defect in the arginase I enzyme.
      Unlike other urea cycle disorders, this condition is not generally associated
      with a hyperammonemic encephalopathy in the neonatal period. It typically
      presents later in childhood between 2 and 4 years of age with predominantly
      neurological features. If untreated, it progresses with gradual developmental
      regression. A favorable outcome can be achieved if dietary treatment and
      alternative pathway therapy are instituted early in the disease course. With this
      approach, further neurological deterioration is prevented and partial recovery of
      skills ensues. Early diagnosis of this disorder through newborn screening
      programs may lead to a better outcome. This review article summarizes the
      clinical characterization of this disorder; as well as its biochemical,
      enzymatic, and molecular features. Treatment, prenatal diagnosis and diagnosis
      through newborn screening are also discussed.

PMID- 16602096
TI  - Retraction.

PMID- 16602097
TI  - Duplication of 5q15-q23.2: case report and literature review.
AB  - BACKGROUND: Pure partial trisomy of chromosome 5q is rare and cases have ranged
      over the entire region, making it difficult to describe a good phenotypic
      correlation to the cytogenetic duplication. CASE: We present a 4.5-year-old girl
      with a de novo direct duplication of chromosome 5q15-q23.2. She has moderate
      developmental delay with lack of speech, microcephaly, and subtle dysmorphic
      features including prominent forehead, bulbous nose, epicanthic folds, protruding
      tongue, and slightly posteriorly-rotated ears. CONCLUSIONS: A comparison is made
      with other similar duplication cases reported in the literature and a general
      description of a proximal 5q duplication phenotype is given, with lack of speech
      as the principal feature.

PMID- 16602098
TI  - Inborn errors of metabolism: new challenges with expanded newborn screening
      programs.

PMID- 16602099
TI  - Biochemical findings in common inborn errors of metabolism.
AB  - The application of tandem mass spectrometry (MS/MS) to newborn screening has led
      to the detection of patients with a wider spectrum of inborn errors of
      metabolism. A definitive diagnosis can often be established early enough to start
      treatment before symptoms appear. Here, we review common biochemical findings in
      disorders caused by deficiency of 3-methylcrotonyl-CoA carboxylase, isobutyryl
      CoA dehydrogenase, 2-methyl-3-hydroxybutyryl-CoA dehydrogenase, 3-ketothiolase, 2
      methylbutyryl-CoA dehydrogenase, and medium chain acyl CoA dehydrogenase. The
      diagnosis of these disorders requires biochemical confirmation by measurement of
      plasma acylcarnitine profile, urine organic acids, and urine acylglycine profiles
      followed by measurement of enzyme activity or detection of causative mutations.
      Early treatment can improve the outcome of these disorders.

PMID- 16602100
TI  - Glutaric acidemia type 1.
AB  - Glutaric acidemias comprise different disorders resulting in an increased urinary
      excretion of glutaric acid. Glutaric acidemia type 1 (GA-1) is an autosomal
      recessive disorder of lysine, hydroxylysine, and tryptophan metabolism caused by
      deficiency of glutaryl-CoA dehydrogenase. It results in the accumulation of 3
      hydroxyglutaric and glutaric acid. Affected patients can present with brain
      atrophy and macrocephaly and with acute dystonia secondary to striatal
      degeneration in most cases triggered by an intercurrent childhood infection with
      fever between 6 and 18 months of age. This disorder can be identified by
      increased glutaryl (C5DC) carnitine on newborn screening. Urine organic acid
      analysis indicates the presence of excess 3-OH-glutaric acid, and urine
      acylcarnitine profile shows glutaryl carnitine as the major peak. Therapy
      consists in carnitine supplementation to remove glutaric acid, a diet restricted
      in amino acids capable of producing glutaric acid, and prompt treatment of
      intercurrent illnesses. Early diagnosis and therapy reduce the risk of acute
      dystonia in patients with GA-1.

PMID- 16602101
TI  - Isovaleric acidemia: new aspects of genetic and phenotypic heterogeneity.
AB  - Isovaleric acidemia (IVA) is an autosomal recessive inborn error of leucine
      metabolism caused by a deficiency of the mitochondrial enzyme isovaleryl-CoA
      dehydrogenase (IVD) resulting in the accumulation of derivatives of isovaleryl
      CoA. It was the first organic acidemia recognized in humans and can cause
      significant morbidity and mortality. Early diagnosis and treatment with a protein
      restricted diet and supplementation with carnitine and glycine are effective in
      promoting normal development in severely affected individuals. Both intra- and
      interfamilial variability have been recognized. Initially, two phenotypes with
      either an acute neonatal or a chronic intermittent presentation were described.
      More recently, a third group of individuals with mild biochemical abnormalities
      who can be asymptomatic have been identified through newborn screening of blood
      spots by tandem mass spectrometry. IVD is a flavoenzyme that catalyzes the
      conversion of isovaleryl-CoA to 3-methylcrotonyl-CoA and transfers electrons to
      the electron transfer flavoprotein. Human IVD has been purified from tissue and
      recombinant sources and its biochemical and physical properties have been
      extensively studied. Molecular analysis of the IVD gene from patients with IVA
      has allowed characterization of different types of mutations in this gene. One
      missense mutation, 932C>T (A282V), is particularly common in patients identified
      through newborn screening with mild metabolite elevations and who have remained
      asymptomatic to date. This mutation leads to a partially active enzyme with
      altered catalytic properties; however, its effects on clinical outcome and the
      necessity of therapy are still unknown. A better understanding of the
      heterogeneity of this disease and the relevance of genotype/phenotype
      correlations to clinical management of patients are among the challenges
      remaining in the study of this disorder in the coming years.

PMID- 16602103
TI  - Perception of heaviness in Parkinson's disease.
AB  - The present study investigated whether a specific aspect of proprioception, the
      sense of heaviness or weight is affected in PD. We determined detection
      thresholds for the perception of a gravito-inertial load in 10 PD patients and 11
      age-matched control subjects. A gradually increasing weight was applied to the
      index finger by means of two slings of different width (low vs. high skin
      pressure). For the controls, mean detection thresholds were 31.3 g at skin high
      pressure and 33.0 g under low pressure. PD patients revealed significantly higher
      thresholds than the control group in both pressure conditions (mean high
      pressure,47.7 g; mean low pressure, 52.3 g; group effect, P = 0.001). Thresholds
      of PD patients tended to increase with disease severity as measured by the
      Unified Parkinson's Disease Rating Scale Motor score (r = 0.55) but did not
      correlate significantly with levodopa equivalent dosage. The results demonstrate
      that the perception of heaviness or weight is already affected in the early
      stages of PD. These findings underline the growing evidence that proprioceptive
      and possibly haptic dysfunction is a common feature of PD.

PMID- 16602102
TI  - Disorders of carnitine transport and the carnitine cycle.
AB  - Carnitine plays an essential role in the transfer of long-chain fatty acids
      across the inner mitochondrial membrane. This transfer requires enzymes and
      transporters that accumulate carnitine within the cell (OCTN2 carnitine
      transporter), conjugate it with long chain fatty acids (carnitine palmitoyl
      transferase 1, CPT1), transfer the acylcarnitine across the inner plasma membrane
      (carnitine-acylcarnitine translocase, CACT), and conjugate the fatty acid back to
      Coenzyme A for subsequent beta oxidation (carnitine palmitoyl transferase 2,
      CPT2). Deficiency of the OCTN2 carnitine transporter causes primary carnitine
      deficiency, characterized by increased losses of carnitine in the urine and
      decreased carnitine accumulation in tissues. Patients can present with
      hypoketotic hypoglycemia and hepatic encephalopathy, or with skeletal and cardiac
      myopathy. This disease responds to carnitine supplementation. Defects in the
      liver isoform of CPT1 present with recurrent attacks of fasting hypoketotic
      hypoglycemia. The heart and the muscle, which express a genetically distinct form
      of CPT1, are usually unaffected. These patients can have elevated levels of
      plasma carnitine. CACT deficiency presents in most cases in the neonatal period
      with hypoglycemia, hyperammonemia, and cardiomyopathy with arrhythmia leading to
      cardiac arrest. Plasma carnitine levels are extremely low. Deficiency of CPT2
      present more frequently in adults with rhabdomyolysis triggered by prolonged
      exercise. More severe variants of CPT2 deficiency present in the neonatal period
      similarly to CACT deficiency associated or not with multiple congenital
      anomalies. Treatment for deficiency of CPT1, CPT2, and CACT consists in a low-fat
      diet supplemented with medium chain triglycerides that can be metabolized by
      mitochondria independently from carnitine, carnitine supplements, and avoidance
      of fasting and sustained exercise.

PMID- 16602104
TI  - Regional brain volumes distinguish PSP, MSA-P, and PD: MRI-based clinico
      radiological correlations.
AB  - Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are
      neurodegenerative disorders, each with a prevalence of around 5 per 100,000.
      Regional brain atrophy patterns differ in the two disorders, however, and
      magnetic resonance imaging is sometimes helpful in distinguishing them in the
      later stages. We measured whole brain and regional volumes, including cerebellum,
      pons, midbrain, superior cerebellar peduncle (SCP), and ventricular volumes as
      well as frontal and posterior-inferior cerebral regions in 18 subjects with PSP,
      9 with MSA-P (parkinsonian phenotype), 9 with Parkinson's disease (PD), and 18
      healthy controls. Associations between these volumes, cognitive profiles, and
      clinical measures of disease severity and motor disability were assessed. Mean
      midbrain volume was 30% smaller in PSP than in PD or controls (P < 0.001) and 15%
      smaller than in MSA-P (P = 0.009). The mean SCP volume in PSP was 30% smaller
      than in MSA-P, PD, or controls (P < 0.001). Mean cerebellar volumes in MSA-P were
      20% smaller than in controls and PD and 18% smaller than in PSP (P = 0.01). Mean
      pontine volume in MSA-P was 30% smaller than in PD or controls (P < 0.001) and
      25% smaller than in PSP (P = 0.01). Motor disability was most strongly associated
      with midbrain volume, and more severe executive dysfunction was associated with
      reduced frontal volume. These distinct patterns of cortical and subcortical
      atrophy, when considered together rather than independently, better differentiate
      PSP and MSA-P from each other and also from healthy controls.

PMID- 16602105
TI  - Isolated high-frequency jaw tremor relieved by botulinum toxin injections.
AB  - Jaw tremor can be seen as a component of various neurological disorders such as
      essential tremor, Parkinson's disease, dystonia, branchial myoclonus, hereditary
      geniospasm, task-specific tremor, and Whipple's disease, as well as in normal
      situations such as shivering, and subclinical physiological jaw tremor. In most
      of these conditions, the jaw tremor is usually associated with tremor or other
      abnormal involuntary movements affecting additional body parts, and its frequency
      is lower than 12 Hz. Schrag and colleagues reported a patient with a high
      frequency idiopathic jaw tremor, and they speculated it could be related to
      orthostatic tremor affecting the masseter muscles. We encountered a similar
      patient with intermittent rapid focal jaw tremor that was successfully treated
      with botulinum toxin injections to the masseters.

PMID- 16602106
TI  - Prevalence of dystonia in Akita Prefecture in Northern Japan.
AB  - We investigated the prevalence of dystonia in Akita Prefecture (population was
      1,166,967 as of 1 November 2004). The prevalence of primary generalized and focal
      dystonia is estimated to be 0.68 and 14.4 per 100,000 persons, respectively.
      Blepharospasm is the most common primary dystonia in this area.

PMID- 16602107
TI  - Survival of Parkinson's disease patients in a large prospective cohort of male
      health professionals.
AB  - Parkinson's disease (PD) patients have higher mortality than individuals without
      PD. However, most of the previous studies were based on prevalent cases and few
      examined the potential effects of duration and smoking on the survival of PD
      patients. We compared the survival experience of 288 men with incident PD
      diagnosed between 1986 and 2000 with that of 51,012 men free of PD in the Health
      Professionals Follow-up Study. As of January 2002, 92 deaths occurred among PD
      cases and 8,485 among men without PD. After controlling for age, men with PD had
      60% higher mortality than those without PD (95% CI: 1.3-2.0). PD mortality was
      strongly related to disease duration: compared with men without PD, the age
      adjusted relative risk for PD patients was 1.1 during the first 5 years from
      diagnosis, 2.3 from 5 to 10 years, and 3.5 after 10 years (P < 0.0001 for trend).
      As expected, cigarette smoking was strongly and positively associated with total
      mortality among men free of PD (comparing >30 pack-years vs. never smokers,
      relative risk, 2.0; P < 0.0001 for trend), but this association was not observed
      among PD patients (RR: 1.0; P = 0.95 for trend). This study confirms that PD
      patients have a higher mortality than individuals without PD and that the excess
      mortality increases with disease duration. However, smoking seems to impose
      little additional risk among PD patients in this large cohort of health
      professionals.

PMID- 16602108
TI  - In vivo three-dimensional motion analysis of the forearm with radioulnar
      synostosis treated by the Kanaya procedure.
AB  - Attempts to separate congenital radioulnar synostosis and restore forearm
      rotation had been disappointing until a new mobilization technique was developed
      by Kanaya and colleagues using free vascularized fascio-fat graft interposition.
      This technique provides a functional rotation arc, but postoperative forearm
      motion is difficult to evaluate given the inaccuracies in determining the range
      of motion and rotational axis using conventional x-rays or computed tomography.
      This study represents an attempt to analyze in vivo three-dimensional motion of
      the forearm with radioulnar synostosis treated by Kanaya's operation using a
      markerless bone registration technique. Six patients with seven postoperative
      forearms (six with congenital and one with posttraumatic radioulnar synostosis)
      underwent 3D computed tomography with the forearm in neutral, fully pronated, and
      fully supinated positions. Range of motion according to this method was 30 +/- 18
      degrees, significantly smaller than the 82 +/- 29 degrees from manual
      examination. Improvements in range of motion were significantly greater in cases
      without dislocation of the radial head (46 +/- 13 degrees) than in cases with
      dislocation (19 +/- 10 degrees). Dislocation of the radial head was also
      significantly correlated with an abnormal axis of rotation of the forearm.

PMID- 16602109
TI  - How muscles recover from paresis and atrophy after intramuscular injection of
      botulinum toxin A: Study in juvenile rats.
AB  - Botulinum toxin A (BoNT-A) is a potent biological toxin widely used for the
      management of skeletal muscle spasticity or dynamic joint contracture.
      Intramuscular injection of BoNT-A causes muscle denervation, paresis, and
      atrophy. This clinical effect of botulinum toxin A lasts 3 to 6 months, and
      injected muscle eventually regains muscle mass and recovers muscle function. The
      goal of the present study was to characterize the molecular and cellular
      mechanisms leading to neuromuscular junction (NMJ) regeneration and skeletal
      muscle functional recovery after BoNT-A injection. Fifty-six 1-month-old Sprague
      Dawley rats were used. Botulinum toxin A was injected into the left gastrocnemius
      muscle at a dosage of 6 units/kg body weight. An equivalent volume of saline was
      injected into the right gastrocnemius muscle to serve as control. The
      gastrocnemius muscle samples were harvested from both hind limbs at 3 days, 7
      days, 15 days, 30 days, 60 days, 90 days, 180 days, and 360 days after
      administration of toxin. In addition, the gastrocnemius muscles from 1-month-old
      rats with no injections were harvested to serve as uninjected control group.
      Muscle samples were processed and mRNA was extracted. Real-time polymerase chain
      reaction (PCR) and gene microarray technology were used to identify key molecules
      involved in NMJ stabilization and muscle functional recovery. More than 28,000
      rat genes were analyzed and approximately 9000 genes are expressed in the rat
      gastrocnemius muscle. Seven days following BoNT-A injection, 105 genes were
      upregulated and 59 genes were downregulated. Key molecules involved in
      neuromuscular junction (NMJ) stabilization and muscle functional recovery were
      identified and their time course of gene expression following BoNT-A injection
      were characterized. This animal study demonstrates that following intramuscular
      injection of BoNT-A, there is a sequence of cellular events that eventually leads
      to NMJ stabilization, remodeling, and myogenesis and muscle functional recovery.
      This recovery process is divided into two stages (aneural and neural) and that
      the IGF-1 signaling pathway play a central role in the process.

PMID- 16602110
TI  - Bone grafts prepared with selective cell retention technology heal canine
      segmental defects as effectively as autograft.
AB  - Using a canine critical-size segmental defect model, a two-phased study was
      undertaken to evaluate the healing efficacy of demineralized bone and cancellous
      chips (DBM-CC) enriched with osteoprogenitor cells using a Selective Cell
      Retention (SCR) technology. The goals of this study were: 1) to determine the
      bone-healing efficacy of SCR-enriched grafts versus autograft, and 2) to assess
      the value of clotting SCR-enriched grafts with platelet-rich plasma (PRP). Thirty
      dogs were included in Phase I: 18 dogs were treated with an SCR-enriched DBM-CC
      graft clotted with autologous bone marrow, and were compared to 12 autograft
      controls. In Phase II, 24 animals were divided into 4 groups of 6 animals, each
      treated with a different bone graft material: 1) iliac crest autograft, 2) DBM-CC
      alone, 3) DBM-CC saturated with marrow, and 4) SCR-enriched DBM-CC clotted with
      PRP. All grafts were placed unilaterally in a 21-mm long osteoperiosteal femoral,
      instrumented, critical-size defect. Radiographs were obtained for all animals
      postoperatively and every 4-16 weeks; animals were then sacrificed. All femurs
      were prepared for histology. Femurs in the Phase II study were also analyzed by
      micro-CT. At 16 weeks, healing--defined by bridging bone across the defects--was
      observed in 50% of the DBM-CC alone group and 67% of the DBM-CC saturated with
      marrow group; 100% of the autograft and SCR-enriched DBM-CC groups were healed.
      Histologically, grafts clotted with PRP showed more mature bone than those
      implanted with autologous bone, which in turn were similar to those implanted
      with bone marrow clotted SCR-enriched grafts. These results demonstrated that: 1)
      SCR-enriched DBM-CC was equivalent to autograft to repair critical-size defects,
      and 2) while not statistically significant, PRP may have accelerated bone
      maturation when used to clot osteoprogenitor-enriched DBM-CC grafts--as compared
      to cell-enriched, DBM-CC grafts without PRP--in large animal models.

PMID- 16602111
TI  - Anticancer effects of zoledronic acid against human osteosarcoma cells.
AB  - Based on neoadjuvant chemotherapy, the prognosis of osteosarcoma patients has
      improved dramatically. However, due to therapy resistance in patient subgroups,
      the development of new treatment strategies is still of utmost importance. The
      aim of our study was to test the effects of the nitrogen-containing
      bisphosphonate zoledronic acid (ZOL) on osteosarcoma cell lines (N = 9). Exposure
      to ZOL at low micromolar concentrations induced a dose- and time-dependent block
      of DNA synthesis and cell cycle progression followed by microfilament breakdown
      and apoptosis induction. The ZOL-induced cell cycle accumulation in S phase was
      accompanied by significant changes in the expression of cyclins and cyclin
      dependent kinase inhibitors with a prominent loss of cyclin E and D1. ZOL not
      only inhibited growth but also migration of osteosarcoma cells. The mevalonate
      pathway intermediary geranyl-geraniol (GGOH) but not farnesol (FOH) significantly
      inhibited the anticancer effects of ZOL against osteosarcoma cells.
      Correspondingly, ZOL sensitivity correlated with the blockade of protein
      geranylgeranylation indicated by unprenylated Rap1. Overexpression of even high
      levels of P-glycoprotein, as frequently present in therapy-resistant
      osteosarcomas, did not impair the anticancer activity of ZOL. Summarizing, our
      data suggest that ZOL, which selectively accumulates in the bone, represents a
      promising agent to improve osteosarcoma therapy.

PMID- 16602112
TI  - Sleep complaints and their relation with drug treatment in patients suffering
      from Parkinson's disease.
AB  - The aim of this research was to quantify sleep problems in patients suffering
      from Parkinson's disease by means of the new Parkinson's Disease Sleep Scale
      (PDSS) and to correlate such problems with the possible influence of current drug
      treatment. A total of 70 patients (36 men and 34 women) with a diagnosis of
      Parkinson's disease were enrolled. Their mean age was 69.7 +/- 8.2 years, and
      duration of disease was 7.4 +/- 4.8 years. All patients completed the PDSS and
      the Unified Parkinson's Disease Rating Scale (UPDRS Parts I-IV). Drug consumption
      and doses were registered. The mean score on the PDSS scale was 109.23 +/- 19.75
      and on the UPDRS III scale was 25.24 +/- 11.35. The lowest scores were obtained
      in Item 3 (sleep fragmentation): 5.53 (2.46); and in Item 8 (nocturia): 5.75
      (2.91). There was a weak correlation between the PDSS and UPDRS III (cc = -0.355,
      P = 0.003), PDSS and UPDRS I (cc = -0.272, P = 0.02), and PDSS and UPDRS IV (cc =
      -0.416, P < 0.001). Motor conditions, mental state, and drug complications
      influence sleep quality. Although this effect was significant, it was not of a
      great magnitude. Dopaminergic drugs did not increase daytime sleepiness. As a
      whole, sleep quality in patients who took dopaminergic agonists did not differ
      from that of patients who took levodopa in monotherapy.

PMID- 16602114
TI  - Effect of shoulder tightness on glenohumeral translation, scapular kinematics,
      and scapulohumeral rhythm in subjects with stiff shoulders.
AB  - Shoulder tightness may cause altered kinematics and lead to development of
      subacromial impingement, tendinitis, and degenerative changes. In this
      investigation, the humeral head translations, scapular kinematics, and
      scapulohumeral rhythm were determined with a three-dimensional electromagnetic
      tracking device during arm elevations in six subjects with anterior shoulder
      tightness and in six subjects with posterior shoulder tightness to study the
      effects of anterior/posterior tightness on shoulder kinematics. Subjects with
      anterior tightness showed lower slopes in curves of glenohumeral elevation
      plotted against scapular upward rotation (scapulohumeral rhythm, 0.11 to 0.32; p
      = 0.021) and less posterior scapular tilt (2.9 to 7.5 degrees; p = 0.002) during
      arm elevations when compared to the group with posterior tightness. The humeral
      head was positioned less posteriorly (2.2 to 3.4 mm; p = 0.004) and more
      superiorly (3.8 to 7.0 mm; p < 0.0005) during arm elevation in subjects with
      posterior tightness. The alternations in shoulder kinematics between subjects
      with anterior and posterior shoulder tightness may be relevant to the development
      of subacromial impingement, tendinitis, and degenerative changes as seen in
      subjects with stiff shoulders.

PMID- 16602113
TI  - Analysis of 14 LRRK2 mutations in Parkinson's plus syndromes and late-onset
      Parkinson's disease.
AB  - The pleomorphic pathology of postmortem LRRK2-positive patients and the frequent
      association with late-onset Parkinson's disease (LOPD) symptoms suggest that
      LRRK2 mutations may play a role in Parkinson's Plus disorders and LOPD. Published
      studies primarily focus on the common G2019S mutation. Analysis of a spectrum of
      LRRK2 mutations in Parkinson's Plus disorders has yet to be reported. We
      investigated 14 leucine-rich repeat kinase 2 (LRRK2) mutations in a cohort of
      Parkinson's Plus disorders and LOPD. A total of 458 patients with progressive
      supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal ganglionic
      degeneration (CBGD), atypical Parkinsonism (AP), and LOPD were screened for 14
      mutations that span exons 19 to 41 of the LRRK2 gene. Among the LOPD cases, 1
      patient was found to harbor the R1441C mutation. He presented with typical
      features of PD at age of 58 years old and responded well to levodopa. We did not
      detect any of the 14 mutations in PSP, MSA, CBGD, and AP patients. We highlight
      the first case of LRRK2 R1441C mutation in late onset sporadic PD of non-European
      ancestry. Furthermore, extensive mutational screen found LRRK2 mutations to be
      rare among patients who presented with PSP, MSA, CBGD, and AP.

PMID- 16602115
TI  - QCT versus DXA in 320 survivors of childhood cancer: association of BMD with
      fracture history.
AB  - PURPOSE: To assess agreement on diagnosis of diminished bone mineral density
      (BMD) and correlation between BMD values obtained by dual-energy X-ray
      absorptiometry (DXA) and quantitative computed tomography (QCT) in childhood
      cancer survivors. PATIENTS AND METHODS: We retrospectively reviewed lumbar spine
      QCT and DXA studies for BMD in patients who underwent both imaging studies within
      a 24-hr period. We determined correlation between BMD values and agreement on
      diagnosis of diminished BMD obtained by both modalities. Diminished BMD was
      defined as two or more SDs below mean for age- and gender-matched reference
      values. We evaluated the relationship of BMD values determined by each modality
      to self-reported fracture history in the 160 (50%) patients with available
      reports. RESULTS: Of 320 patients, 56% (178) were male; 87% (277) were white.
      Median age was 16.4 (range, 5.1-36.0) years. Median BMD Z-score was -1.43 (range,
      -5.96 to 3.20) by QCT and -1.30 (range, -5.50 to 2.80) by DXA. Correlation
      between QCT- and DXA-determined BMD values was significant but low, and agreement
      on diminished BMD was fair (kappa = 0.32). There was no association between BMD
      measured by either QCT or DXA and self-reported traumatic fracture history. Male
      gender was associated with doubling the traumatic fracture risk (P = 0.0499).
      CONCLUSIONS: Quantitative computed tomography and DXA may give discrepant results
      when used to assess bone health in childhood cancer survivors, especially in
      those of non-white race. This inconsistency in indicators of BMD deficiency may
      complicate clinical decision-making. Consecutive use of a single modality is
      recommended to provide reliable longitudinal information.

PMID- 16602116
TI  - Body composition and bone mass in survivors of childhood cancer.
AB  - BACKGROUND: The number of survivors of childhood cancer has increased. Several
      studies in children and adults have shown relationships between lean mass (LM),
      fat mass (FM), and bone mineral content (BMC). The objective of the study was to
      examine the association between body composition and bone mass in young survivors
      of childhood cancer. METHODS: Sixty-eight postpubertal participants (31 females
      and 37 males) aged between 15.5 and 27 years who were at least 5 years after
      completion of treatment for leukemia (n = 30), lymphoma (n = 28), or solid tumors
      (n = 10) were studied. Anthropometry was performed and dual energy X-ray
      absorptiometry (DXA) was used to assess BMC in the total body (T) and lumbar
      spine (S), FM, and LM. RESULTS: There were no observed differences in age or time
      for cessation of treatment. Body mass index (BMI) was a strong determinant of
      bone mass in both sexes. TBMC correlated positively with LM (males r = 0.9 and
      females r = 0.76; P < 0.0001, respectively) and with FM (r = 0.54; P < 0.01 in
      males and r = 0.8; P < 0.00001 in females). SBMC correlated with LM in both sexes
      (in males r = 0.77 and in females r = 0.64; P < 0.0001, respectively) but only in
      females, SBMC also correlated positively with FM (r = 44 P = 0.03). There were no
      differences between patients who received radiation and those who did not.
      CONCLUSIONS: The associations between bone mass and body composition differ by
      sex and skeletal site, however, they are similar in survivors of childhood cancer
      and compared to healthy individuals during growth. Further prospective research
      is needed in cancer survivors to determine the long-term effect of anti-cancer
      therapy on body composition and bone mass.

PMID- 16602117
TI  - Ceftriaxone induced hemolysis complicated by acute renal failure.
AB  - Over the last decade, second and third generation cephalosporins have been the
      most common drugs causing hemolytic anemia (HA). Of these cases, 20% have been
      attributed to ceftriaxone. The clinical presentation of ceftriaxone-induced HA is
      usually abrupt with sudden onset of pallor, tachypnea, cardio-respiratory arrest
      and shock. Acute renal failure (ARF) has been reported in 41% of such cases with
      a high fatality rate. We report a pediatric patient with ARF complicating
      ceftriaxone-induced HA who survived. Ceftriaxone is a commonly used drug, and
      early recognition of HA and institution of supportive care, including dialysis is
      likely to improve the outcome.

PMID- 16602118
TI  - Bone mineral density in children and young adults with beta-thalassemia major
      conventionally treated.

PMID- 16602119
TI  - Late effects risk profiles using the long-term follow-up guidelines in identical
      twin survivors of acute lymphoblastic leukemia.
AB  - As the number of pediatric cancer survivors increases, the cost of cure (i.e.,
      late effects) needs to be measured through a consistent mechanism. Through the
      use of the Children's Oncology Group's (COG) Long-Term Follow-Up (LTFU)
      guidelines, individualized risk profiles can be discerned for each off-therapy
      patient. These guidelines were used to compare and contrast risk profiles for
      identical twin females treated for acute lymphoblastic leukemia (ALL). The first
      twin was treated for high-risk leukemia and the second for standard-risk
      leukemia, each with different ALL protocols. Timely use of the LTFU guidelines
      has aided in identifying and treating their adverse late effects.

PMID- 16602120
TI  - Improved outcome in childhood acute myeloid leukemia in Singapore with the MRC
      AML 10 protocol.
AB  - BACKGROUND: The introduction of the United Kingdom Medical Research Council's
      10th AML trial (MRC AML 10) protocol incorporating high-dose anthracycline
      therapy has improved outcome of children with acute myeloid leukemia (AML). In
      this study, we review the results of childhood AML therapy in a Singapore
      university hospital over the last 17 years emphasizing toxicity and outcome.
      PROCEDURE: Retrospective analysis revealed 34 children with AML between 1988 and
      2003. Prior to September 1996, therapy consisted of: POG-8498 (n = 10), others (n
      = 9). From September 1996, all but one of 15 children received MRC AML 10
      treatment. RESULTS: At the time of analysis, 17 had died from disease, and 17
      patients were alive among whom 2 had relapsed. MRC AML 10-treated patients (n =
      14) had significantly better 3-year overall, event-free, and disease-free
      survival (74% vs. 35%, 77% vs. 20%, 83% vs. 31%; P = 0.019, P = 0.002, and P =
      0.010, respectively) and were likelier to achieve complete remission (CR) than
      non-MRC AML 10 patients (P = 0.102). Among patients who achieved CR, MRC AML 10
      treated patients were significantly more likely to achieve CR after only one
      cycle of chemotherapy (P = 0.016). Hematologic toxicity was similar among the
      different regimens (P = 0.9). CONCLUSIONS: These findings suggest that MRC AML 10
      treatment results in significantly superior survival, without excess toxicity.
      Future studies should attempt to elucidate the relative importance of individual
      MRC AML 10 components and reduce the high cumulative anthracycline dose without
      compromising outcome.

PMID- 16602121
TI  - Bacteria and cell cytocompatibility studies on coated medical grade titanium
      surfaces.
AB  - Acute and chronic osteomyelitis caused by staphylococci can be difficult to treat
      by conventional means and often has marked consequences for the patient. Current
      methods of treatment involve the use of systemic antibiotics, the local
      implantation of nondegradable drug carriers, and surgical debridement. A possible
      solution that could prevent initial bacterial adhesion could be to modify the
      implant surface with an antimicrobial coating while maintaining biocompatibility
      to host cells. This study describes the cytocompatibility evaluation of different
      coatings (poly(D,L-lactide) (PDLLA), politerefate (PTF), calcium phosphate/anodic
      plasma-chemical treatment (CaP/APC), polyurethane (PU), and polyvinylpyrollidone
      (PVP) on titanium surfaces with and without chlorhexidine diacetate (CHA) to
      Staphylococcus aureus, Staphylococcus epidermidis, and hTERT human fibroblasts.
      Surface characterization of the coatings showed no significant variation in the
      roughness or hydrophobicity of the coated surfaces, except the CaP/APC surface
      that was porous yet the smoothest, and PVP, PVP+CHA, and CaP/APC+CHA that were
      more hydrophilic in nature than the others. On the surfaces without CHA, both
      staphylococcal strains and spread fibroblasts were observed, but on the CHA
      impregnated surfaces few bacteria and no intact fibroblasts were seen. Flow
      cytometry found fewer bacteria in the media and on the surfaces containing CHA in
      comparison to the surfaces without CHA. The release kinetics varied from slow
      (over 200 h) to burst release: PDLLA>PTF>PU>CaP/APC=PVP. This study showed that
      PDLLA and PTF have the best potential as coatings on implants for drug delivery,
      as they were cytocompatible to hTERT fibroblasts, eluted CHA effectively, and
      passed mechanical testing. The actual release kinetics of PDLLA and PTF are
      important, as the amount of CHA present should remain above the minimal
      inhibitory concentration value for a limited time before disappearing completely.

PMID- 16602122
TI  - Growth behavior of rat bone marrow cells on RF magnetron sputtered hydroxyapatite
      and dicalcium pyrophosphate coatings.
AB  - The aim of this study was to evaluate the osteogenic properties of magnetron
      sputtered dicalcium pyrophaosphate (DCPP) and hydroxylapatite (HA) coatings.
      Therefore, DCPP and HA coatings were deposited on grit-blasted titanium discs.
      The substrates were used as-prepared or received an additional heat treatment
      which changed the amorphous coating structure to a crystalline structure.
      Subsequently, rat bone marrow stromal cells were cultured for 1-24 days on the
      various substrates. DNA and alkaline phosphatase activity was determined after 1,
      3, 5, 8, and 12 days of incubation. Osteocalcin expression was evaluated after 8,
      12, 16, and 24 days of incubation. Scanning electron microscopical analysis of
      cell morphology and coating characteristics was done after 8 and 16 days of
      incubation. All assays were done in duplicate and in each assay all specimens
      were present in fourfold. Results demonstrated that the cells did not proliferate
      and differentiate on all amorphous coatings. SEM revealed that the amorphous
      coatings showed significant dissolution. On the crystalline DCPP and HA coatings
      an increase in DNA and alkaline phosphatase activity was seen starting at day 8
      of incubation. Osteocalcin expression on the crystalline coatings started to
      increase at day 16 of incubation. SEM showed that the growth and differentiation
      of the cells was associated with extensive collagen fiber formation and surface
      mineralization in the form of globular accretions. Further, statistical testing
      revealed that proliferation and differentiation of the rat bone marrow stromal
      cells started significantly earlier on the crystalline HA coatings than that on
      the crystalline DCPP coatings. These results demonstrate that the rat bone marrow
      stromal cells proliferated and differentiated only on crystalline magnetron
      sputtered DCPP as well as HA coatings, which warrants the further in vivo
      analysis of the bone healing supporting properties of these coatings.

PMID- 16602123
TI  - In vivo effects of BISGMA-a component of dental composite-on male mouse
      reproduction and fertility.
AB  - The aim of this study is to investigate the effects of the resin monomer
      bisphenol A glycerolate dimethacrylate (BISGMA) on adult male mouse fertility.
      Male Swiss mice were administered various concentrations of BISGMA (0, 25, and
      100 microg/kg) for a period of 28 days, and the effects on fertility was assessed
      by breeding these males with untreated female mice after the exposure periods.
      The results showed that fertility was significantly reduced when male mice were
      exposed to BISGMA, in comparison with their control counterparts. In females
      mated with males exposed to BISGMA, there was a significant reduction in the
      pregnancy rates as well as the number of viable fetuses. The number of
      resorptions out of the total number of implantations was significantly increased
      in females mated with males that had been exposed to BISGMA. Furthermore, the
      number of females with resorptions was also significantly increased. Significant
      reductions in bodyweight and weights of the testis and preputial glands were also
      observed. The weights of the seminal vesicles were significantly increased in
      males exposed to BISGMA in comparison with their control counterparts. There were
      significant reductions in testicular sperm counts, epididymal sperm counts and in
      the efficiency of sperm production. In conclusion, exposure of male mice to
      BISGMA results in an impairment of the reproductive system and fertility.

PMID- 16602124
TI  - Adhesion of mesenchymal stem cells to polymer scaffolds occurs via distinct ECM
      ligands and controls their osteogenic differentiation.
AB  - The osteogenic potential of mesenchymal stem cells (MSCs) cultured on
      poly(lactide-co-glycolide) (PLGA) or poly(caprolactone) (PCL), two widely used
      polymeric biomaterials that have been reported to differentially support
      osteogenic differentiation, was compared in these studies. Here we report that
      MSCs cultured in 3-D PLGA scaffolds for up to 5 weeks significantly upregulate
      osteocalcin gene expression levels. By contrast, osteocalcin expression was
      markedly downregulated in 3-D PCL-based constructs over the same time course. We
      hypothesized that differential adsorption of extracellular matrix (ECM) proteins
      present in serum-containing culture medium and subsequent differences in integrin
      mediated adhesion are responsible for these differences, and tested this
      hypothesis using thin (2-D) polymeric films. Supporting this hypothesis,
      significant amounts of fibronectin and vitronectin deposited onto both materials
      in serum-containing osteogenic media, with type-I collagen present in lower
      amounts. Adhesion-blocking studies revealed that MSCs adhere to PCL primarily via
      vitronectin, while type-I collagen mediates their attachment to PLGA. These
      adhesive mechanisms correlated with higher levels of alkaline phosphatase (ALP)
      activity after 2 weeks of monolayer culture on PLGA versus PCL. These data
      suggest that the initial adhesion of MSCs to PLGA via type-I collagen fosters
      osteogenesis while adhesion to PCL via vitronectin does not, and stress the need
      for an improved molecular understanding of cell-ECM interactions in stem cell
      based therapies.

PMID- 16602125
TI  - A novel ultra high molecular weight polyethylene-hyaluronan microcomposite for
      use in total joint replacements. I. Synthesis and physical/chemical
      characterization.
AB  - A novel microcomposite between ultra high molecular weight polyethylene (UHMWPE)
      and hyaluronan (HA) was developed to create a hydrophilic and lubricious UHMWPE
      surface for total joint replacement and other biomedical load-bearing
      applications. Preforms with interconnected micropores were used as the UHMWPE
      starting material to form a microcomposite with HA, rather than starting with
      fully dense, bulk UHMWPE. HA was silylated first to increase its hydrophobicity
      and compatibility with UHMWPE. The silylated groups were removed through
      hydrolysis prior to final compression molding. A uniform and enzymatic
      degradation resistant HA film layer was produced on the microcomposite surface,
      which quickly hydrated in water, forming a lubricious surface film that was fully
      wetted by water drops during contact angle measurements. Presence of HA film on
      the composite surface was also demonstrated through X-ray photoelectron
      spectroscopy analysis and Toluidine Blue O dye assay. The mechanical and
      tribological properties evaluation of the novel microcomposites are presented in
      Part II.

PMID- 16602126
TI  - Hydrophilic molecularly imprinted poly(hydroxyethyl-methacrylate) polymers.
AB  - Highly cross-linked 2-hydroxyethyl methacrylate (HEMA) and poly(ethylene glycol)
      dimethacrylate with poly(ethylene glycol) of molecular weight 600 (PEG600DMA)
      were molecularly imprinted with hydrophilic templates glucose and proxyphylline
      using water as a solvent. Glucose-imprinted polymers showed increased recognitive
      capacity compared to nonimprinted polymers as well as increased glucose uptake
      compared to structurally similar galactose and methylglucopyranoside. Increasing
      glucose concentration in the imprinting mixture resulted in higher capacity and
      selective binding. Similar results were obtained for proxyphylline-imprinted
      P(HEMA-co-PEG600DMA) polymers, where the proxyphylline uptake was higher than
      structurally similar theophylline. Glucose-imprinted networks also showed
      diffusion coefficients on the order of 10(-6) cm2/s, conducive to applications in
      drug delivery and tissue engineering. This work showed that using pairs of
      hydrogen-bonding monomers and templates, selective, high-affinity sites could be
      created despite nonspecific binding.

PMID- 16602127
TI  - Catheter management of aortic valve stenosis in neonates and children.
AB  - Therapy for severe aortic valve stenosis in infants and children has shifted from
      the operating suite to the catheterization laboratory and even to the bedside as
      a direct result of improved catheter technology, evolving techniques, and
      comparable results to conventional surgical intervention. This review summarizes
      the brief history pertaining to the various techniques and outcomes of
      transcatheter balloon valvuloplasty in infants and children with critical or
      severe aortic valve stenosis.

PMID- 16602129
TI  - Twin probes as a novel tool for the detection of single-nucleotide polymorphisms.
AB  - Single-nucleotide polymorphisms (SNPs) are the most common form of DNA sequence
      variation. There is a strong interest from both academy and industry to develop
      rapid, sensitive and cost effective methods for SNP detection. Here we report a
      novel structural concept for DNA detection based on fluorescence dequenching upon
      hybridization. The so-called "twin probe" consists of a central fluorene
      derivative as fluorophore to which two identical oligonucleotides are covalently
      attached. This probe architecture is applied in homogeneous hybridization assays
      with subsequent fluorescence spectroscopic analysis. The bioorganic hybrid
      structure is well suited for sequence specific DNA detection and even SNPs are
      identified with high efficiency. Additionally, the photophysical properties of
      the twin probe were investigated. The covalent attachment of two single stranded
      oligonucleotides leads to strong quenching of the central fluorescence dye
      induced by the nucleobases. The twin probe is characterized by supramolecular
      aggregate formation accompanied by red-shifted emission and broad fluorescence
      spectra.

PMID- 16602128
TI  - Detection of vulnerable plaque in a murine model of atherosclerosis with optical
      coherence tomography.
AB  - OBJECTIVES: The aim of this study was to evaluate the feasibility of optical
      coherence tomography (OCT) to identify the components of vulnerable plaques in a
      well-established murine model of human atherosclerosis. BACKGROUND: Although the
      pathologic features that predict plaque rupture at autopsy are well known, the
      development of a technology to identify these high risk features in vivo is
      lacking. OCT uses reflected light to provide histology-like images of plaque with
      higher resolution than competing imaging modalities. Whether OCT can reliably
      identify the features of an atherosclerotic plaque that define it as vulnerable
      thin fibrous cap, large lipid core, and high percent of lipid in the artery
      requires further study. METHODS: OCT images of the atherosclerotic innominate
      artery segments from the apolipoprotein E knockout (apoE(-/-)) mice were recorded
      and correlated with histology in both in vivo (n = 7) and well as in ex vivo
      experiments (n = 12). RESULTS: Excellent correlation between the OCT and
      histology measurements for fibrous cap thickness, lipid core size, and percentage
      lipid content was found. The fibrous cap thicknesses examined span those of human
      fibrous caps known to rupture (< 65 microm). Regions of greatest light reflection
      in OCT images were observed when calcium hydroxy-apatite was scattered in lipid,
      less in fibrous tissue, and least in lipid. CONCLUSIONS: These findings suggest
      that OCT holds promise for the identification of features defining vulnerable
      plaque including fibrous cap thickness, lipid core size, and the percentage of
      lipid content.

PMID- 16602130
TI  - CaCO3-poly(methyl methacrylate) nanoparticles for fast enrichment of low
      abundance peptides followed by CaCO3-core removal for MALDI-TOF MS analysis.

PMID- 16602131
TI  - Multiplexed DNA detection with biobarcoded nanoparticle probes.

PMID- 16602132
TI  - Are aluminoxanes nanotubular? Structural evidence from a quantum chemical study.

PMID- 16602133
TI  - C-type natriuretic peptide for reduction of restenosis: gene transfer is superior
      over single peptide administration.
AB  - BACKGROUND: Restenosis is still a significant clinical problem limiting the long
      term therapeutic success following balloon dilation or stent implantation. New
      approaches are necessary inhibiting neointima formation and simultaneously
      promoting re-endothelialization. Therefore, long-term therapeutic effects of
      adventitial liposome-mediated C-type natriuretic protein (CNP) gene and CNP
      peptide applications in a porcine model for restenosis post-angioplasty were
      investigated. METHODS: For in vitro applications, primary cultures of porcine
      vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) were used. Gene
      transfer was performed with cationic lipid DOCSPER [1,3-dioleoyloxy-2-(N5
      carbamoylspermine)propane]. In vivo treatment of pig femoral arteries was
      adventitial using a needle injection catheter following balloon angioplasty.
      Arteries were investigated by angiography, Evan's blue staining,
      histomorphometry, immunohistochemistry, PCR and RT-PCR. RESULTS: Using CNP gene
      transfer in vitro, 29.4+/-7.2% reduction of cell proliferation in VSMCs was
      observed. In ECs, the CNP gene did not compromise cellular growth. For the CNP
      peptide the optimal concentration was 1 mM with 50.7+/-11.3% reduction of VSMC
      proliferation and 12.1+/-5.3% enhancement of growth of ECs. Three weeks following
      application in vivo complete re-endothelialization was observed in all treated
      groups. At 3 months significant reduction of neointima formation was observed
      using CNP gene vs. CNP peptide (85.9+/-7.8% vs. 63.3+/-27.6% reduction, P<0.05)
      compared to control treatment. CONCLUSION: Periadventitial liposome-mediated CNP
      gene transfer in vivo resulted in a significant long-term reduction of neointima
      formation without compromising endothelial repair and was superior over single
      CNP peptide administration. Advantages of CNP are its physiological origin and
      simultaneous inhibition of VSMC proliferation and promotion of EC growth.

PMID- 16602135
TI  - A validated high-performance liquid chromatographic assay for determination of
      lumiracoxib in human plasma.
AB  - Lumiracoxib {2-[(2-fluoro-6-chlorophenyl)amino]-5-methyl-benzeneacetic acid} is a
      highly selective and potent cyclooxygenase-2 (COX-2) inhibitor, which is
      chemically distinct from other coxibs in that it contains a carboxylic group and
      is weakly acidic. In the present study, a liquid-liquid extraction-based reversed
      phase HPLC method with UV detection was validated and applied for the analysis of
      lumiracoxib in human plasma. The analyte was separated on a reversed-phase column
      with acetonitrile and 0.05% trichloracetic acid in water (35:65, v/v) as mobile
      phase at a flow rate of 1 mL/min, and UV detection at 270 nm. The retention times
      for lumiracoxib and niflumic acid (internal standard) were 16.9 and 10.4 min,
      respectively. The validated quantitation range for lumiracoxib was 10-10,000
      ng/mL. The developed procedure was applied to assess the pharmacokinetics of
      lumiracoxib following administration of a single oral 200 mg dose to a healthy
      male volunteer.

PMID- 16602134
TI  - Bioluminescence imaging after HSV amplicon vector delivery into brain.
AB  - BACKGROUND: Firefly luciferase (Fluc) has routinely been used to quantitate and
      analyze gene expression in vitro by measuring the photons emitted after the
      addition of ATP and luciferin to a test sample. It is now possible to replace
      luminometer-based analysis of luciferase activity and measure luciferase activity
      delivered by viral vectors directly in live animals over time using digital
      imaging techniques. METHODS: An HSV amplicon vector expressing Fluc cDNA from an
      inducible promoter was delivered to cells in culture and into the mouse brain. In
      culture, expression of Fluc was measured after induction in a dose-dependent
      manner by a biochemical assay, and then confirmed by Western blot analysis and
      digital imaging. The vectors were then stereotactically injected into the mouse
      brain and Fluc expression measured non-invasively using bioluminescence imaging.
      RESULTS: Rapamycin-mediated induction of Fluc from an HSV amplicon vector in
      culture resulted in dose-dependent expression of Fluc when measured using a
      luminometer and by digital analysis. In mouse cortex, a single injection of an
      HSV amplicon vector (2 microl, 1x10(8) transducing units (t.u.)/ml) expressing
      Fluc from a viral promoter (CMV) was sufficient to detect robust luciferase
      activity for at least 1 week. Similarly, an HSV amplicon vector expressing Fluc
      under an inducible promoter was also detectable in the mouse cortex after a
      single dose (2 microl, 1x10(8) t.u./ml) for up to 5 days, with no detectable
      signal in the uninduced state. CONCLUSIONS: This HSV amplicon vector-based system
      allows for fast, non-invasive, semi-quantitative analysis of gene expression in
      the brain.

PMID- 16602136
TI  - Selection and combination of machine learning classifiers for prediction of
      linear B-cell epitopes on proteins.
AB  - Recently, new machine learning classifiers for the prediction of linear B-cell
      epitopes were presented. Here we show the application of Receiver Operator
      Characteristics (ROC) convex hulls to select optimal classifiers as well as
      possibilities to improve the post test probability (PTP) to meet real world
      requirements such as high throughput epitope screening of whole proteomes. The
      major finding is that ROC convex hulls present an easy to use way to rank
      classifiers based on their prediction conservativity as well as to select
      candidates for ensemble classifiers when validating against the antigenicity
      profile of 10 HIV-1 proteins. We also show that linear models are at least
      equally efficient to model the available data when compared to multi-layer feed
      forward neural networks.

PMID- 16602137
TI  - Generation of cell hybrids via a fusogenic cell line.
AB  - BACKGROUND: Hybrids obtained by fusion between tumour cells (TC) and dendritic
      cells (DC) have been proposed as anti-tumour vaccines because of their potential
      to combine the expression of tumour-associated antigens with efficient antigen
      presentation. The classical methods used for fusion, polyethylene glycol (PEG)
      and electrofusion, are cytotoxic and generate cell debris that can be taken up by
      DC rendering the identification of true hybrids difficult. METHODS: We have
      established a stable cell line expressing a viral fusogenic membrane glycoprotein
      (FMG) that is not itself susceptible to fusion. This cell line has been used to
      generate hybrids and to evaluate the relevance of tools used for hybrid
      detection. RESULTS: This FMG-expressing cell line promotes fusion between
      autologous or allogeneic TC and DC in any combination, generating 'tri-parental
      hybrids'. At least 20% of TC are found to be integrated into hybrids.
      CONCLUSIONS: It is speculated that this tri-parental hybrid approach offers new
      possibilities to further modulate the anti-tumour effect of the DC/TC hybrids
      since it allows the expression of relevant immunostimulatory molecules by
      appropriate engineering of the fusogenic cell line.

PMID- 16602138
TI  - [A child with apnoea].
AB  - This is a case report of a girl, from the age 73 days to 5 years and 173 days ,
      who during sleep had 127 episodes of apnoea (lasting 20-55 seconds) accompanied
      by colour shifts. In her first year of life she had 21 episodes of apnoea, in the
      second 21, in the third 36, in the fourth 22, in the fifth year 7, and during the
      first 6 months of the sixth year there were 2 episodes of apnoea. An explanation
      was never found in spite of investigations aiming at cardiopulmonary,
      neurological or metabolic disease. The staff never verified episodes of apnoea
      during admittances to hospital wards. The episodes were merely observed by the
      mother, the father and the grandmother, but the circumstances were persuasive. In
      addition to episodes of apnoea she had symptoms of dysfunction of the autonomous
      nervous system, i.e. facial colour shift and sweating without apnoea or exercise.
      She had frequent attacks of abdominal colic until aged two and a half years. It
      has not been possible to give a clear-cut diagnosis. It is hypothesized that she
      suffers from a mild form of a disease entity covering a wide spectrum from
      Ondine's curse (Congenital central hypoventilation syndrome) to remittent
      Apparent life-threatening events (ALTEs) and Sudden infant death syndrome (SIDS).

PMID- 16602139
TI  - [Autonomic dysfunction--an overlooked physiopathologic mechanism?].

PMID- 16602140
TI  - National strategy for pandemic influenza released; $3.8 billion appropriated for
      pandemic preparedness.

PMID- 16602142
TI  - National Science Advisory Board for Biosecurity reviews papers, holds second
      meeting.

PMID- 16602141
TI  - Recent developments in the creation of a national health information network.

PMID- 16602143
TI  - HHS proposes changes to federal quarantine regulations.

PMID- 16602145
TI  - The global approach.

PMID- 16602144
TI  - Three-year program to discuss voluntary measures to strengthen the biological
      weapons convention concluded.

PMID- 16602146
TI  - Hot and sexy moulds!

PMID- 16602147
TI  - Diagnosis of abiotic and biotic stress factors using the visible symptoms in
      foliage.
AB  - Visible symptoms in the foliage of trees are recorded to monitor the effects of
      abiotic and biotic stress. Difficulties are reported in diagnosing the origin of
      stress. The present paper discusses several diagnostic criteria which are usable
      in different species for a better determination of the stress factor type. A new
      diagnosis scheme to differentiate between classes of abiotic and biotic stress
      factors is supplied. Abiotic stress generates gradients of symptoms. The symptom
      specificity is determined by the degree of interaction between the stress factor
      and plant defense system. Symptoms caused by abiotic stress and natural autumnal
      senescence can be morphologically different or undistinguishable according to the
      stress and plant species. With biotic stress, the class of parasitic is generally
      recognizable on the basis of the visible symptoms. Structurally and
      physiologically based explanations of the symptom morphology are still missing
      for many stress factors.

PMID- 16602148
TI  - Letrozole or tamoxifen in early breast cancer.

PMID- 16602149
TI  - Letrozole or tamoxifen in early breast cancer.

PMID- 16602150
TI  - Benazepril for advanced chronic renal insufficiency.

PMID- 16602151
TI  - Febuxostat versus allopurinol for gout.

PMID- 16602152
TI  - Hirsutism.

PMID- 16602153
TI  - Testing your diagnostic skills. Case no. 2: cherubism.

PMID- 16602155
TI  - Managers say drop in glove prices will be short-lived.

PMID- 16602156
TI  - For the patient. Managing and treating diabetes.

PMID- 16602157
TI  - For the patient. Addressing cardiovascular health disparities through community
      interventions.

PMID- 16602158
TI  - For the patient. The use of antibiotics among Asian and Pacific Islanders.

PMID- 16602159
TI  - For the patient. What keeps African-American women from exercising?

PMID- 16602160
TI  - For the patient. Are current measures of obesity accurate for all populations?

PMID- 16602161
TI  - For the patient. Reviewing the heart disease risk of multiracial populations.

PMID- 16602162
TI  - For the patient. What women experiencing "the change" should know.

PMID- 16602163
TI  - If physical activity is the answer, what was the question?

PMID- 16602164
TI  - The long sitting screening test in elite cyclists.
AB  - Pelvic rotation during cycling is important because it influences aerodynamics,
      cycling efficiency and the occurrence of overuse injuries. The aim of this study
      was to determine whether or not pelvic position in long sitting influences pelvic
      position during cycling. An observational, cross sectional, within-subjects study
      design was used. Thirty elite international track and road cyclists participated
      as subjects and two measures were undertaken. In long sitting, a digital
      inclinometer was positioned on the lumbosacral junction to give a static measure
      in degrees of sacral inclination (SI) relative to the horizontal. During active
      cycling, video analysis of reflective surface markers over the anterior superior
      iliac spine and posterior superior iliac spine was used to give a measure in
      degrees of anterior pelvic rotation (APR), by the angle between these two
      landmarks and the horizontal. No significant linear relationship was found
      between the two testing positions (r = 0.23, p = 0.22).

PMID- 16602165
TI  - Seasonal changes in power of competitive cyclists: implications for monitoring
      performance.
AB  - Sport scientists should consider seasonal trends and individual variability in
      performance when using tests to track performance changes resulting from training
      or other medium-term interventions with individuals or in research studies. We
      report here the seasonal changes and variability in power of 12 male competitive
      cyclists, who performed laboratory tests of incremental peak and 4-km mean power
      measured with three ergometers simultaneously in each of five sessions during
      three phases (base, pre-comp, comp) of a season. Repeated-measures analysis of
      log-transformed power provided mean percent changes in performance between phases
      and within-cyclist variability in performance expressed as coefficients of
      variation between sessions < or = 2 wk apart within a phase and between sessions
      8 wk-12 wk apart in different phases. Peak power increased from the base phase to
      the pre-comp phase on average by 5.3%, and by a further 1.8% from pre-comp to
      comp phase; corresponding increases in 4-km mean power were 6.1% and 2.2% (90%
      likely limits all approximately +/-2.6%). The variabilities for peak and 4-km
      mean powers were 1.2%-1.8% for sessions separated by < or = 2 wk and 2.0%-2.3%
      for sessions in pre-comp and comp phases, but increased to 3.4%-3.8% for sessions
      between the base and other phases (likely limits approximately (x/)/(1.6).
      Individual differences in the improvement in performance after the base phase
      evidently produced the greater variability between the base and the other phases.
      Interventions that might produce small but worthwhile changes in performance over
      a period of weeks-months need to be researched in pre-comp and comp phases, when
      the variability is small.

PMID- 16602166
TI  - Time-motion analysis of elite field hockey during several games in succession: a
      tournament scenario.
AB  - International field hockey tournaments may require teams to play three games
      within a period of four days. Therefore, there is potential for residual fatigue
      to affect the movement patterns of players during subsequent games. The purpose
      of this study was to document changes in time-motion analysis of 14 elite male
      field hockey players during three games within a period of four days during an
      international tournament. In addition, the nature of and any changes in repeated
      sprint activity were investigated using a criteria of a minimum of three sprints
      with a mean recovery duration between sprints of < 21 s. The percent of total
      game time spent standing significantly increased across all three games (7.4+/
      .2, 11.2+/-2.7 and 15.6+/-5.6%, respectively, P<0.05). Conversely, the percent
      time spent jogging significantly decreased from game 1 to game 2 and from game 1
      to game 3 (40.5+/-7.3, 34.8+/-7.4 and 29.4+/-5.7%, respectively, P<0.05).
      Furthermore, the percent time in striding significantly increased from game 1 to
      game 3 and from game 2 to game 3 (4.1+/-1.3, 5.1+/-0.9 and 5.8+/-1.4%,
      respectively. P<0.05). Changes in mean motion frequency and duration were
      recorded across games for the motions of standing, striding and sprinting. The
      frequency of exercise bouts that met the criteria for 'repeated-sprint' decreased
      across the three games (17, 11 and 8, respectively). In summary, the results
      suggest that when elite field hockey players play three games within four days
      there are significant changes in time-motion analysis.

PMID- 16602167
TI  - Physiological responses during submaximal interval swimming training: effects of
      interval duration.
AB  - The aim of the present study was to determine the time sustained near VO2max in
      two interval training (IT) swimming sessions comprising 4x400 m (IT(4x400)) or
      16x100 (IT(16xl00)). Elite swimmers (Mean+/-SD age 18+/-2 yrs; body mass 66.9+/
      6.5 kg: swim VO2max 55.7+/-5.8 ml.kg(-1).min(-1)) completed three experimental
      sessions at a 50-m indoor pool over a one week period. The first test comprised a
      5 x 200-m incremental test to exhaustion for determination of the pulmonary
      ventilation threshold (VT, m.s(-1)), VO2max, the velocity associated with VO2max
      (VO2max, m(s(-1)) and maximum heart rate (HR(max), b.min(-1)). The remaining two
      tests involved the IT(4x400) and IT(16xl00) performed in a randomised order. The
      two IT sessions where completed at a velocity representing 25% of the difference
      between the VT and the VO2max (delta25%) and in the same work to rest ratio.
      During the IT sessions VO2 as well as HR were measured. The duration (s) >90%
      VO2max, also the duration (s) >90% HR(max), were not significantly different in
      the IT(16x100) and IT(4x400). However, limits of agreement (LIM(AG)) analysis
      demonstrated considerable individual variation in the time >90% VO2max (mean
      difference +/-2SD = 222+/-819 s) and the time >90% HRmax (mean difference +/-2SD
      = 61+/-758 s) between the two IT sessions. This factor deserves further research
      to establish the characteristics of those athletes which influence the
      physiological responses in IT of short or longer duration repetitions.

PMID- 16602168
TI  - Comparison of nerve conduction velocities of lower extremities between runners
      and controls.
AB  - Peripheral nerve injuries can occur in runners, but large numbers of nerve
      injuries remain subclinical. Identification of nerve injuries needs an
      understanding of common sites of entrapment in running. Fourteen asymptomatic
      male middle-distance runners and 14 non-active subjects participated in this
      study. The neurophysiologic study consisted of motor and sensory nerve conduction
      of medial and lateral plantar nerves, sensory nerve conduction of sural and
      superficial peroneal nerves, and motor nerve conduction of common peroneal nerve.
      Active range of motion and muscle strength assessment (dorsi flexion/plantar
      flexion; inversion/eversion) as measured using a Biodex System3 Dynamometer were
      observed to be within normal limits for both groups. The medial plantar (sensory)
      nerve and sural nerve distal latencies were significantly prolonged and sensory
      conduction velocities were significantly delayed in the runners compared with the
      control subjects. Many of the asymptomatic runners with abnormal nerve conduction
      tests in this study may represent presymptomatic or asymptomatic neuropathy
      similar to the type of subclinical entrapment neuropathy.

PMID- 16602169
TI  - Effect of gender on lower extremity kinematics during rapid direction changes: an
      integrated analysis of three sports movements.
AB  - Anterior cruciate ligament (ACL) injury is a common sports injury, particularly
      in females. Gender differences in knee kinematics have been observed for specific
      movements, but there is limited information on how these findings relate to other
      joints and other movements. Here we present an integrated analysis of hip, knee
      and ankle kinematics across three movements linked to non-contact ACL injury. It
      was hypothesised that there are gender differences in lower extremity kinematics,
      which are consistent across sports movements. Ten female and ten male NCAA
      basketball players had three-dimensional hip, knee and ankle kinematics
      quantified during the stance phase of sidestep, sidejump and shuttle-run tasks.
      For each joint angle, initial value at contact, peak value and between-trial
      variability was obtained and submitted to a two-way mixed design ANOVA (gender
      and movement), with movement condition treated as a repeated measure. Females had
      higher peak knee valgus and lower peak hip and knee flexion, with the same gender
      differences also existing at the beginning of stance (p<0.05). Peak valgus
      measures were highly correlated between movements, but not to static valgus
      alignment. Kinematic differences demonstrated by females for the sports movements
      studied, and in particular knee valgus, may explain their increased risk of ACL
      injury. These differences appear to stem largely from subject-specific
      neuromuscular mechanisms across movements, suggesting that prevention via
      neuromuscular training is possible.

PMID- 16602170
TI  - Intensity and direction of competitive anxiety as a function of goal attainment
      expectation and competition goal generation.
AB  - Jones's control model was adopted to investigate differences in the labelling of
      symptoms associated with pre-competition anxiety and self-confidence as a
      function of goal attainment expectation and competition goal generation. Team
      sport performers (N = 96) were divided into outcome, performance and process goal
      groups. Anxiety intensity and direction, and self-confidence were then examined
      as a function of goal expectancy (positive or negative) and perceived input into
      goal production (input or no input). MANOVA and follow-up ANOVA supported the
      study predictions. Specifically, participants who reported positive expectations
      of goal achievement and indicated some input into the goal generation process
      experienced the most facilitative interpretations of cognitive symptoms and
      greater self-confidence. The results highlight the need to consider how goals are
      generated when attempting to foster a sense of control and help athletes cope
      with the psychological demands of competition.

PMID- 16602171
TI  - Hospitalisation due to sports-related injuries among children and adolescents in
      New South Wales, Australia: an analysis on socioeconomic and geographic
      differences.
AB  - This population-based epidemiological study aims to investigate the associations
      between socioeconomic status, geographic location, and sports-related injuries
      among children and adolescents in New South Wales (NSW), Australia. Data utilised
      in this study were collected as part of the routine vital health information
      system via all hospitals in NSW. Included were all patients aged between 5-19
      years admitted to a hospital because of sports-related injuries in NSW between
      1996 and 2000. The crude age-and-sex-specific hospitalisation rates (/100,000
      population-years) by socioeconomic levels and geographic residential locations
      were calculated. Negative Binomial regression analyses were also performed to
      examine the associations between socioeconomic status, geographic location and
      the rate of hospitalisation after adjusting for the age and sex of children and
      adolescents. The results indicated a significant association between geographic
      location and hospitalisation due to sports-related injury, after adjusting for
      age, sex, and socioeconomic status. The risk of hospital admission with sports
      related injury among children and adolescents in rural areas was nearly 10%
      higher than for those in the metropolitan areas (RR=1. 12, 95%C.I.=1.07-1.32)).
      However, no association between socioeconomic status and hospitalisation with
      sports-related injury was found. Greater efforts are required in the
      implementation of safety strategies in research, training, and education for the
      prevention of sports-related injury in rural areas.

PMID- 16602172
TI  - Lipid metabolism in young men after acute resistance exercise at two different
      intensities.
AB  - The aim of this study was to examine the effects of different resistance training
      loads on blood lipids. Six healthy, untrained male volunteers performed three
      protocols: control (no exercise), high intensity (HI) and low intensity (LI)
      exercise seven days apart. Each protocol comprised eight exercises. The HI
      protocol used a 10-repetition maximum (RM) load and 10 repetitions. In the LI
      protocol, the load was halved and repetitions doubled. The volume of work
      performed in the two exercise protocols was identical. Blood samples were
      collected before, immediately after, and 15 min after each protocol and analysed
      for total, high density (HDL-C), low density cholesterol and triglyceride. The
      only significant effect of exercise was to acutely increase HDL-C in the
      immediate post exercise sample compared with the control. There was no
      significant effect on any lipid fraction resulting from the LI protocol compared
      with the control. The results of this study suggest that intensity alone has an
      effect in determining the HDL-C response to acute resistance exercise.

PMID- 16602173
TI  - Promoting physical activity to older adults: a preliminary evaluation of three
      general practice-based strategies.
AB  - The aim of this study was to explore the feasibility of an exercise scientist
      (ES) working in general practice to promote physical activity (PA) to 55 to 70
      year old adults. Participants were randomised into one of three groups: either
      brief verbal and written advice from a general practitioner (GP) (G1, N=9): or
      individualised counselling and follow-up telephone calls from an ES, either with
      (G3, N=8) or without a pedometer (G2, N=11). PA levels were assessed at week 1,
      after the 12-wk intervention and again at 24 weeks. After the 12-wk intervention,
      the average increase in PA was 116 (SD=237) min/wk: N=28, p<0.001. Although there
      were no statistically significant between-group differences, the average
      increases in PA among G2 and G3 participants were 195 (SD=207) and 138 (SD=315)
      min/wk respectively, compared with no change (0.36, SD=157) in G1. After 24
      weeks, average PA levels remained 56 (SD=129) min/wk higher than in week 1. The
      small numbers of participants in this feasibility study limit the power to detect
      significant differences between groups, but it would appear that individualised
      counselling and follow-up contact from an ES, with or without a pedometer, can
      result in substantial changes in PA levels. A larger study is now planned to
      confirm these findings.

PMID- 16602174
TI  - Sea-level performance in runners using altitude tents: a field study.
AB  - In this study of effects of simulated altitude exposure on sea-level performance,
      10 competitive runners slept in a hypoxic environment achieved with tents for
      9.8+/-1.3 h.d(-1) (mean+/-standard deviation) for 24 days-30 days at 2500-3500 m
      (PIO2=117-103 mmHg) above sea level. The altitude group and a control group of 10
      runners performed usual training (PIO2=149 mmHg). At approximately 4-wk intervals
      before and after exposure both groups performed an incremental test for lactate
      threshold. The altitude group performed an additional test, a treadmill run to
      exhaustion lasting approximately 5 min. One week following exposure lactate
      threshold speed of the altitude group relative to the control group increased by
      1.2% (90% likely limits +/-3.1%), but the effect became slightly negative after
      controlling for baseline differences in running speed between the groups. A 16%
      increase in time to exhaustion was observed in the altitude group, equivalent to
      a 1.9% (+/-1.4%) increase in speed in a time trial. Change in performance had an
      unclear relationship to total altitude exposure, genotype for angiotensin
      converting enzyme, and change in haemoglobin concentration. Our findings are
      consistent with little or no effect of use of altitude tents on sea-level
      performance.

PMID- 16602175
TI  - Incontinence--an aggressive approach to treatment: a case series.
AB  - Recent evidence suggests that, for some, leaking urine may be a barrier to
      physical activity. Although important from a lifestyle point of view, bladder
      problems and incontinence also affect both men and women socially,
      psychologically and economically. For example, it can be particularly distressing
      when incontinence occurs post-prostate surgery, especially if these patients were
      continent before surgery. This case series outlines an aggressive, innovative,
      exercise-based approach to the management of stress incontinence post
      prostatectomy. The program attempts to enhance neuromuscular and vascular systems
      associated with continence, with emphasis placed on the abdominal and pelvic
      floor muscles. The program was undertaken by 14 incontinent post-prostatectomy
      patients (mean age 63.5 y, using a mean of 3.5 sanitary pads per day). The
      program was initiated a mean of two months post-op and had a mean duration of six
      months. Upon completion of the program. 10 patients were found to be completely
      dry with three retaining a small leakage (a few drops). The 14th could not comply
      with the program because of illness. The results of this study appear promising
      in this patient population. There are indications for further research.

PMID- 16602176
TI  - Diabetes basics. Taking medicines. How to get them down smoothly.

PMID- 16602177
TI  - Your healthy heart. Sudden death. The power of prevention.

PMID- 16602178
TI  - Winning at weight loss. Small losses, big gains. Shedding even a little excess
      weight improves your health. Support is key to success.

PMID- 16602179
TI  - Winning at weight loss. Around-the-clock weight control. To lose weight and
      improve your health, look for little opportunities all through the day.

PMID- 16602180
TI  - Winning at weight loss. Home cooking, slim style. These weight-loss cooking tips
      go far beyond merely substituting ingredients, and the results are more flavorful
      than ever.

PMID- 16602181
TI  - Winning at weight loss. The drug option. Weight-loss medications can help, but
      they are not side-effect free.

PMID- 16602182
TI  - Winning at weight loss. Stomach surgery for weight loss. For the severely obese,
      this last resort offers impressive benefits. But it's not risk-free.

PMID- 16602183
TI  - Preparing for pregnancy. Tips from former Miss America Nicole Johnson Baker...and
      her doctor.

PMID- 16602185
TI  - Research profile. Foot ulcers. Investigating options for reducing risk. Sheri
      Colberg, PhD.

PMID- 16602184
TI  - By the book. Keep careful records of your blood glucose checks.

PMID- 16602186
TI  - [Seminar in Continuing Medical   education. 4th Yugoslav Symposium on Sarcoidosis
      -"Chronic sarcoidosis--new views on an old problem". Belgrade, 16 and 17 October
      2003].

PMID- 16602187
TI  - Generation of high-energy self-phase-stabilized pulses by difference-frequency
      generation followed by optical parametric amplification.
AB  - We produce ultrabroadband self-phase-stabilized near-IR pulses by a novel
      approach where a seed pulse, obtained by difference-frequency generation of a
      hollow-fiber broadened supercontinuum, is amplified by a two-stage optical
      parametric amplifier. Energies up to 20 microJ with a pulse spectrum extending
      from 1.2 to 1.6 microm are demonstrated, and a route for substantial energy
      scaling is indicated.

PMID- 16602188
TI  - Double-slit interference with Laguerre-Gaussian beams.
AB  - The interference of Laguerre-Gaussian beams carrying orbital angular momentum was
      demonstrated in Young's double-slit geometry. Double-slit interference is shown
      to be affected by the azimuthal phase dependence of a Laguerre-Gaussian beam.
      This interference provides new insight into the helical phase structure of the
      Laguerre-Gaussian beam and has potential applications for measuring the orbital
      angular momentum of an arbitrary wavefront.

PMID- 16602189
TI  - [Lung transplantation for cystic fibrosis: infectious events].
AB  - BACKGROUND AND OBJECTIVE: Lung transplantation is the only treatment for end
      stage lung disease in patients with cystic fibrosis (CF). The presence of
      pathogens in the airways prior to transplantation is a risk factor for infections
      in the post-transplantation period; in fact, infections account for 80% of deaths
      within the first year. Our goal was to analyze the incidence of infectious
      complications in patients who underwent a lung transplantation due to cystic
      fibrosis. PATIENTS AND METHOD: Descriptive transversal study of CF transplanted
      lung patients since the beginning of the transplantation programme (1991 to
      September 2004). We evaluated data regarding opportunistic infections,
      demographical information, lung function, mortality causes and survival. We used
      descriptive statistics and Kaplan Meier for survival. RESULTS: 267 lung
      transplants were done, 57 were due to CF, 30 men and 27 women, with an average
      age of 21 years (7.8 years. The average time on waiting list was 96 days (range 1
      407). 57 bilateral lung transplants, 3 heart-lung transplants and one combined
      liver-lung transplant were performed. All patients received triple
      immunosuppression (tacrolimus/cyclosporine, azathioprine and prednisone). 16
      patients (28%) died: 4 in early postoperative period (7%), 5 at 6 months after
      transplantation, and the remaining 7 patients died several years post
      transplantation. Survival was 82% at one year, 76% at three years, and 65% at
      five years; 75% of our patients survived a mean of 3.56 years. Cytomegalovirus
      (CMV) infections occurred in 26% of patients and were associated with chronic
      rejection (p < 0.05). Purulent bronchitis was the most frequent bacterial
      infection: 59% of cases were caused by multiresistant pathogens. There was a
      8.77% cases of B cepacia infection with 2 patients dying because of it. There
      were 7 cases of airway infection due to Aspergillus fumigatus, and 5 fungal
      invasive forms that were associated with chronic rejection (p < 0.05). Two cases
      of tuberculosis (Mycobacterium tuberculosis) were registered, 1 case of M.
      abcessus lung disease and 1 case of visceral leishmaniosis. Infectious diseases
      accounted for 19% of early and 12% of late mortality. CONCLUSIONS: Although
      serious infections were seen after transplantation in our series, infectious
      events did not represent a high risk of postoperative mortality rate. Fungal
      disease was the only late relevant infectious complication, mainly associated
      with chronic rejections. Close CMV monitoring, and even pre-emptive antifungal
      therapy, are recommended for patients with chronic rejection.

PMID- 16602190
TI  - From surgical pathology... where a nerve root mass has arthritic origin.

PMID- 16602191
TI  - From the operating room... where an old problem is solved by a new technique.

PMID- 16602192
TI  - ME Lynch. A review of the use of methadone for the treatment of chronic noncancer
      pain. Pain Res Manage 2005;10(3):133-44.

PMID- 16602193
TI  - Implicit learning -- explicit knowing: a role for sleep in memory system
      interaction.
AB  - There is evidence that sleep supports the enhancement of implicit as well as
      explicit memories (i.e., two memory systems that during learning normally appear
      to act together). Here, employing a serial reaction time task (SRTT) paradigm, we
      examined the question whether sleep can provide explicit knowledge on an
      implicitly acquired skill. At learning, young healthy subjects (n = 20) were
      first trained on the SRTT. Then, implicit knowledge was assessed on two test
      blocks, in which grammatically incorrect target positions were occasionally
      interspersed by the difference in reaction times between grammatically correct
      and incorrect target positions. To assess explicit sequence knowledge, thereafter
      subjects performed on a generation task in which they were explicitly instructed
      to predict the sequential target positions. In half the subjects, learning took
      place before a 9-hour retention interval filled with nocturnal sleep (sleep
      group), in the other half, the retention interval covered a 9-hour period of
      daytime wakefulness (wake group). At subsequent retesting, both testing on the
      generation task and the SRTT test blocks was repeated. At learning before the
      retention interval, subjects displayed significant implicit sequence knowledge
      which was comparable for the sleep and wake groups. Moreover, both groups did not
      display any explicit sequence knowledge as indicated by a prediction performance
      not differing from chance on the generation task. However, at retesting, there
      was a distinct gain in explicit knowledge in the subjects who had slept in the
      retention interval, whereas generation task performance in the wake group
      remained at chance level. SRTT performance in the test blocks at retesting did
      not indicate any further gain in skill (i.e., unchanged reaction time differences
      between grammatically correct and incorrect target positions) independently of
      whether subjects had slept or remained awake after learning. Our results indicate
      a selective enhancement of explicit memory formation during sleep. Because before
      sleep subjects only had implicit knowledge on the sequence of target transitions,
      these data point to an interaction between implicit and explicit memory systems
      during sleep-dependent off-line learning.

PMID- 16602194
TI  - Analysis of physical and chemical parameters of bottled drinking water.
AB  - Seventeen different brands of bottled drinking water, collected from different
      retail shops in Amritsar, were analyzed for different physical and chemical
      parameters to ascertain their compliability with the prescribed/recommended
      limits of the World Heath Organization (WHO) and the United States Environmental
      Protection Agency (USEPA). It was found that the majority of the brands tested
      were over-treated. Lower values of hardness, total dissolved solids (TDS) and
      conductance than the prescribed limits of WHO showed that water was deficient in
      essential minerals. Minerals like magnesium, potassium, calcium and fluoride were
      present in some cases in such a low concentration that water seemed to be as good
      as distilled water. Samples showing fluoride lesser than 0.5 mg/l warranted
      additional sources of fluoride for the people consuming only bottled water for
      drinking purposes. Zero values for chlorine demand as shown by all the bottled
      water samples showed that water samples were safe from micro-organisms. In case
      of heavy metals, only lead had been found to be greater than the limit of 0.015
      mg/l as prescribed by WHO and USEPA, in seven out of 17 samples. Lead even at
      such a low concentration can pose a great health hazard.

PMID- 16602195
TI  - Acute neuropathic joint disease: a medical emergency?

PMID- 16602196
TI  - Resistance to insulin therapy among patients and providers: results of the cross
      national diabetes attitudes, wishes, and needs (DAWN) study.

PMID- 16602197
TI  - Beneficial effects of a Dietary Approaches to Stop Hypertension eating plan on
      features of the metabolic syndrome.

PMID- 16602198
TI  - Maintenance of certification for family physicians.

PMID- 16602199
TI  - Preparing for a pandemic: concern over a possible avian flu pandemic is moving
      states, communities and the federal government to action.

PMID- 16602200
TI  - A new Medicaid: new federal law gives state officials greater latitude in shaping
      Medicaid reforms.

PMID- 16602201
TI  - Uncharted territory: current trends in Section 1115 demonstrations.

PMID- 16602202
TI  - Erythema induratum: a case of mistaken identity.

PMID- 16602203
TI  - Recombinant activated factor VII for bleeding in patients without inherited
      bleeding disorders.
AB  - (1) Recombinant activated factor VII (rFVIIa) is licensed in Canada for the
      prevention and treatment of bleeding in hemophiliacs, but it is increasingly used
      to control bleeding in non-hemophilic patients during surgery, or during
      treatment for severe trauma or intracerebral hemorrhage (ICH). (2) In one
      clinical trial, there was a significant reduction in mortality among patients
      with ICH treated with rFVIIa. In another trial, administration of rFVIIa
      significantly reduced the number of trauma patients needing massive blood
      transfusions although there was no significant difference in mortality. (3)
      Adequately powered randomized controlled trials are needed to clarify the
      efficacy and safety of rFVIIa for non-bleeding disorder indications. Phase III
      trials in ICH and trauma are underway. (4) There is potential for non-hemophilic
      use, particularly if clinical efficacy and cost effectiveness are established.

PMID- 16602204
TI  - Conversation with Joseph Gusfield.

PMID- 16602205
TI  - Bridging the gap: the role of individual health insurance coverage.

PMID- 16602206
TI  - Consent, frozen embryos, procreative choice and the ideal family.

PMID- 16602207
TI  - MMR: medicine, mothers and rights.

PMID- 16602209
TI  - A new direction on DNA?

PMID- 16602208
TI  - Misapplied ethical considerations: U.S. federal stem cell mandates lack global
      focus and market foresight.

PMID- 16602210
TI  - Necessity, private defence and the killing of Mary.
AB  - This article examines the reasons used by the Court of Appeal in Re A (Children)
      to authorise and justify an operation which would inevitably kill the weaker of a
      pair of conjoined twins in order to offer the stronger twin a good chance of a
      long and happy life. The crux of the judgment was that a utilitarian theory of
      necessity could justify this operation. This article seeks to define the criminal
      law defences at issue in the case and to argue that utilitarian necessity is such
      a dangerous doctrine that it should never be employed if there is any other
      defence which can be made to serve the same purpose--as there was in the present
      case.

PMID- 16602211
TI  - Risperidone: new indication. Behavioural disorders in children with autism or
      mental disabilities: no progress.
AB  - (1) Sedative drugs are one option when autistic or mentally disabled children
      have behavioural disorders that place them (or other people) in physical danger.
      Among the classic neuroleptics, haloperidol is the drug with the best-documented
      efficacy and safety. Placebo-controlled trials have also shown lithium to be
      effective for this use. (2) Clinical evaluation of risperidone in children with
      mental disabilities includes 3 placebo-controlled double-blind trials, 2 of which
      involved 118 and 110 children aged from 5 to 12 years who were treated for 6
      weeks. All 3 trials showed a partial behavioural improvement in about 75% of
      children receiving risperidone, versus about 30% of children in the placebo
      groups. (3) Clinical evaluation of risperidone in autistic children includes 2
      placebo-controlled double-blind trials involving 110 and 79 children who were
      treated for 8 weeks. One of these studies has been published in detail: 69% of
      children partially improved with risperidone, versus 12% of the children on
      placebo. (4) Given the absence of clinical trials comparing risperidone with
      haloperidol or lithium, there is no evidence that risperidone is more effective
      than these other treatments. (5) The principal adverse events observed in short
      term trials of risperidone were drowsiness (affecting about 50% of children),
      weight gain (about 1.2 kg per month during the first months of treatment), and
      hyperprolactinaemia (affecting about 12% of children). Extrapyramidal disorders
      were infrequent during short-term trials, but their incidence reached about 25%
      after a year of risperidone treatment. (6) The impact of long-term risperidone
      therapy on growth and mental development is not known. (7) In France treatment is
      about 7 times more expensive with risperidone than with haloperidol. (8) In
      practice, the risk-benefit balance of risperidone in the treatment of autistic or
      mentally disabled children with behavioural disorders is no better overall than
      that of older products such as haloperidol and lithium, which, in the absence of
      anything better, remain the standard drugs.

PMID- 16602212
TI  - The phoenix of abortional freedom: is a penumbral or Ninth-Amendment right about
      to arise from the nineteenth-century legislative ashes of a fourteenth-century
      common-law liberty?

PMID- 16602213
TI  - An ethics ensemble: abortion, Thomson, Finnis and the case of the violin-player.
AB  - This paper considers approaches to the ethics of abortion and putative links to
      "rights" debates. In particular, it revisits two papers on the topic from the
      early 1970's, written by Judith Jarvis Thomson and John Finnis respectively.
      Consideration of the discourse produced by these papers to some extent reveals
      the strategic importance of linguistic and conceptual organisation--the
      rhetorical forces underlying claims to disinterested, analytical standing. In
      particular, the paper reviews the practical ethics analogy proposed by Thomson;
      the deployment of "Hohfeldian" rights analysis by John Finnis, the link to the
      abortion debate and the broader implications of such deployment in its relation
      to current "rights" discourse.

PMID- 16602214
TI  - Moving from voluntary euthanasia to non-voluntary euthanasia: equality and
      compassion.
AB  - The recent Dutch law legalising active voluntary euthanasia will reignite the
      euthanasia debate. An illuminating method for evaluating the moral status of a
      practice is to follow the implications of the practice to its logical conclusion.
      The argument for compassion is one of the central arguments in favour of
      voluntary active euthanasia. This argument applies perhaps even more forcefully
      in relation to incompetent patients. If active voluntary euthanasia is legalised,
      arguments based on compassion and equality will be directed towards legalising
      active non-voluntary euthanasia in order to make accelerated termination of death
      available also to the incompetent. The removal of discrimination against the
      incompetent has the potential to become as potent a catch-cry as the right to
      die. However, the legalisation of non-voluntary euthanasia is undesirable. A
      review of the relevant authorities reveals that there is no coherent and workable
      "best interests" test which can be invoked to decide whether an incompetent
      patient is better off dead. This provides a strong reason for not stepping onto
      the slippery path of permitting active voluntary euthanasia.

PMID- 16602215
TI  - Joy to the world! A (healthy) child is born! Reconceptualizing 'harm' in wrongful
      conception.
AB  - The wrongful conception action holds both a troubled past and future. As a
      response to rapid technological advancement in the area of reproduction, this
      action has introduced complex legal and ethical issues in the courts' efforts to
      respond to the question: 'Can parenthood ever constitute an injury?' At the heart
      of this dilemma lies the manner by which both law and society conceptualize
      'harm'--is this 'part of the normal vicissitudes of life' or a harmful event? But
      this question is not decided within a legal vacuum and public policy factors have
      deeply influenced the nature and existence of case law in this field. In the
      context of the controversial cases of McFarlane v Tayside Health Board [2000] and
      Rees v Darlington Memorial Hospital [2002], this article critically examines how
      'harm' is judicially characterized and explores the various tensions emerging
      from conflicting harm constructs. In arguing that the courts must seek to find a
      balanced approach between public policy concerns and reproductive autonomy, this
      article will present a fresh theoretical perspective to the conceptualization of
      harm based on autonomy as the central organizing principle.

PMID- 16602216
TI  - [Lofgren's syndrome (acute sarcoidosis)].

PMID- 16602217
TI  - [Quality of life after superficial femoral vein harvest for infra-inguinal
      reconstructions].
AB  - BACKGROUND: The superficial femoral vein (SFV) is a well-established alternative
      conduit for infra-inguinal reconstructivenous hypertension after SFV harvest may
      however result in significant morbidity. This study reports the efficiency of SFV
      as conduit for infra-inguinal reconstructions and characterize the anatomic and
      physiologic changes in harvest limbs and their relationship to the development of
      venous complications. METHODS: From May 1999 through November 2003, 23 SFV were
      harvested from 21 patients undergoing infra-inguinal reconstructions. Bypasses
      were controlled by regular duplex-ultrasound. The venous morbidity was assessed
      by measurements of leg circumferences, strain-gauge plethysmography and quality
      of life, investigated by the VEINES-QOL scale. RESULTS: At a mean follow-up of
      10.4 months (range 1-56), primary, secondary patency and limb salvage rates of
      infra-inguinal bypasses using SFV are 71.4%, 76.2% and 85.7% respectively. No
      patient had major venous claudication. Oedema was significantly present in nine
      patients. Strain-gauge plethysmography showed outflow obstruction in all
      patients. The VEINES-QOL assessment showed no limitation in social and domestic
      activity, moderate complain about leg heaviness despite presence of oedema.
      CONCLUSION: The SFV harvest is a reliable conduit for infra-inguinal
      reconstructions and results in moderate venous morbidity in terms of functional
      consequences and quality of life.

PMID- 16602218
TI  - [Anatomy and physiopathology of venous system].
AB  - The field of chronic venous disease has suffered from a lack of precision in
      diagnosis. This deficiency has led to conflicting reports in studies of
      management of specific venous problem. The establishment of an uniform language
      for classifying the findings of CVD was needed. In 1995, the CEAP classification
      was proposed for classification and grading of CVD on the basis of clinical
      manifestations (C), etiologic factors (E), anatomic distribution of involvement
      (A) and underlying pathophysiologic findings (P). The purpose was to provide a
      comprehensive objective classification that could be used world-wide and serve as
      a basis for more scientific analysis of management alternatives.

PMID- 16602220
TI  - [Iliac vein compression syndrome, the "May Thurner Syndrome"].
AB  - The May Thurner Syndrome is a thrombosis of the left iliac vein due to the
      compression of the common iliac vein by the right common iliac artery. This
      results in intimal wall changes of the vein with secondary thrombosis. The
      treatment of choice is enovascular with thrombolysis followed by angioplasty with
      stenting.

PMID- 16602219
TI  - [Deep vein thrombosis: epidemiology, risk factors and natural history].
AB  - Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major sources of
      morbidity and mortality. In young individuals the incidence of DVT is of
      1/100,000 people; at middle age it is approximately 1/1000, which is also the
      overall incidence; thereafter, it increases steeply and in old age approaches
      1%/year. DVT is a multifactorial disease involving a variety of risk factors,
      many of which are common. It is nowadays accepted that the interaction of
      multiple risk factors over time determines the risk of thrombosis.

PMID- 16602221
TI  - [Surgery for deep venous reflux in the lower limb].
AB  - The effectiveness of the deep venous reconstructive surgery (DVRS) for reflux
      remains controversial. The more common etiology in deep venous reflux (DVR) is
      the postthrombotic syndrome, but primary deep vein insufficiency is frequently
      overshadowed. Valve agenesis is very rare. Clinical examination frequently does
      not allow distinguishing between superficial and deep venous insufficiency. In
      addition primary reflux is difficult to identify from secondary deep reflux.
      INVESTIGATIONS: Duplex scanning provides etiologic, anatomic and hemodynamic
      information. Plethysmography gives information on the overall severity of the
      venous disease, but not on the etiology and is not reliable for identifying the
      predominant component when superficial and deep insufficiencies are combined. It
      would seem logical to go beyond these investigations only in those patients in
      whom surgery for DVR may be considered. In absence of contraindication
      (uncorrectable coagulation disorder, ineffective calf pump) complementary
      investigations must be carried out: ambulatory venous pressure measurement and
      venography including ascending and descending phlebography. The goal of DVR
      surgery is to correct the reflux related to deep venous insufficiency at
      subinguinal level. But it must be kept in mind that DVR is frequently combined
      with superficial and perforator reflux, consequently all these mechanisms have to
      be corrected in order to reduce the ambulatory venous pressure. Surgical
      techniques can be classified into 2 groups: those with phlebotomy and those
      without. Outcomes DVRS for reflux are difficult to assess as this surgery is
      frequently combined with superficial and perforator vein surgery, but both have
      been usually performed before as first step. Indication for DVRS relies on
      clinical, hemodynamic and imaging criteria. Etiology is also a decision factor as
      surgery is more often proposed in primary reflux. DVRS must be performed on
      specialized and high-trained centers.

PMID- 16602223
TI  - The Asheville Project: long-term clinical, humanistic, and economic outcomes of a
      community-based medication therapy management program for asthma.
AB  - OBJECTIVE: To assess clinical, humanistic, and economic outcomes of a community
      based medication therapy management (MTM) program for 207 adult patients with
      asthma over 5 years. DESIGN: Quasi-experimental, longitudinal pre-post study.
      SETTING: 12 pharmacy locations in Asheville, N.C. PATIENTS/OTHER PARTICIPANTS:
      Patients with asthma covered by two self-insured health plans; professional
      educator at Mission Hospitals; 18 certificate-trained community and hospital
      pharmacists. INTERVENTIONS: Education by a certified asthma educator; regular
      long-term follow-up by pharmacists (reimbursed for MTM by health plans) using
      scheduled consultations, monitoring, and recommendations to physicians. MAIN
      OUTCOME MEASURES: Changes in forced expiratory volume in 1 second (FEV1), asthma
      severity, symptom frequency, the degree to which asthma affected people's lives,
      presence of an asthma action plan, asthma-related emergency department/hospital
      events, and changes in asthma-related costs over time. RESULTS: All objective and
      subjective measures of asthma control improved and were sustained for as long as
      5 years. FEV1 and severity classification improved significantly. The proportion
      of patients with asthma action plans increased from 63% to 99%. Patients with
      emergency department visits decreased from 9.9% to 1.3%, and hospitalizations
      from 4.0% to 1.9%. Spending on asthma medications increased; however, asthma
      related medical claims decreased and total asthma-related costs were
      significantly lower than the projections based on the study population's
      historical trends. Direct cost savings averaged 725 dollars/patient/year, and
      indirect cost savings were estimated to be 1230 dollars/patient/year. Indirect
      costs due to missed/nonproductive workdays decreased from 10.8 days/year to 2.6
      days/year. Patients were six times less likely to have an emergency
      department/hospitalization event after program interventions. CONCLUSION:
      Patients with asthma who received education and long-term medication therapy
      management services achieved and maintained significant improvements and had
      significantly decreased overall asthma-related costs despite increased medication
      costs that resulted from increased use.

PMID- 16602224
TI  - Community pharmacy managers' perception of computerized drug-drug interaction
      alerts.
AB  - OBJECTIVE: To examine community pharmacists' attitudes toward computerized drug
      drug interaction (DDI) alerts and identify factors associated with more favorable
      perceptions of these alerts. DESIGN: Cross-sectional postal survey. SETTING: 18
      metropolitan statistical areas (MSAs) in the United States. PARTICIPANTS: 3000
      community pharmacy managers. INTERVENTIONS: 34-item survey instrument designed to
      collect data about the pharmacy including demographics, workload issues, handling
      of DDIs, and pharmacists' attitudes toward computerized DDI alerts. MAIN OUTCOME
      MEASURE: Responses to items concerning community pharmacy managers' attitudes
      toward DDI alerts and factors associated with more favorable attitudes toward
      these alerts. RESULTS: A total of 736 usable surveys were returned (25.3%
      response rate). Pharmacy managers generally disagreed that DDI alerts were a
      waste of time (mean +/- SD, 2.1 +/- 1.1 on a scale of 1, strongly disagree, to 6,
      strongly agree). However, they were not completely confident that their computer
      systems provided them with meaningful DDI alerts (mean +/- SD, 4.5 +/- 1.2). They
      were confident in their ability to identify DDIs (mean +/- SD, 4.9 +/- 0.9) and
      discuss DDIs with physicians (mean +/- SD, 5.2 +/- 0.7). Pharmacy software that
      provided detailed DDI information as well as the ability to customize DDI alerts
      were associated with more favorable perceptions of DDI alerts. CONCLUSION:
      Despite being presented with a large proportion of clinically unimportant alerts,
      community pharmacy managers did not believe DDI alerts were meaningless or a
      waste of time. Incorporation of features that streamline DDI alerts may improve
      their effectiveness in community pharmacy practice.

PMID- 16602225
TI  - Workload and availability of technology in metropolitan community pharmacies.
AB  - OBJECTIVE: To assess workload characteristics and the presence of prescription
      processing technologies within metropolitan community pharmacies in the United
      States. DESIGN: Cross-sectional postal survey. SETTING: 18 metropolitan
      statistical areas (MSAs) in the United States. PARTICIPANTS: 3000 managers
      located in community pharmacies processing at least 500 third-party claims per
      month for four major pharmacy benefits managers. INTERVENTIONS: 34-item survey
      instrument designed to collect data about the pharmacy including demographics,
      workload issues, handling of drug-drug interactions (DDIs), and pharmacists'
      attitudes toward computerized DDI alerts. MAIN OUTCOME MEASURES: Workload (hours
      of operation, prescription volume, staffing hours, prescription processing
      intensity) and prescription processing technologies (telecommunication systems,
      automated counting/filling or verification devices, number of computer terminals,
      and computer software vendors). RESULTS: Overall, 736 usable surveys were
      returned (response rate, 25.3%). On average, respondents reported a volume of
      approximately 1340 prescriptions per week processed at a rate of almost 17
      prescriptions per hour. Independent pharmacies processed approximately 3
      prescriptions per hour more than chain pharmacies even though a statistically
      equal or slightly lower proportion of those pharmacies had automated
      technologies. The presence of technology was generally high for all pharmacies,
      particularly countertop tablet/capsule-counting devices and telefacsimile
      machines. The most common software vendors differed considerably between chain
      and independent pharmacies. CONCLUSION: The number of prescriptions processed per
      hour and number of technologies available increased with the total weekly volume
      of prescriptions processed in this national survey. A majority of pharmacies had
      at least one type of automated prescription processing technology and an
      automated telecommunication system for accepting new or refill prescriptions.
      Independent pharmacies processed more prescriptions per hour than did chains but
      did so with fewer categories of technologies.

PMID- 16602226
TI  - Use of herbs and herbal products by Hispanics in south Florida.
AB  - OBJECTIVES: To provide insight into the use of herbs by Hispanic Americans,
      identify specific herbal products that health care professionals should inquire
      about in this population, and assess information sources and expenditures.
      DESIGN: Cross-sectional survey. SETTING: South Florida. PARTICIPANTS: Convenience
      sample of 200 Hispanic adults. INTERVENTIONS: Participants completed a
      descriptive, self-administered survey. MAIN OUTCOME MEASURES: Specific herbs and
      herbal remedies use, monthly expenditures, sources of information, and attitudes
      and beliefs regarding herbs. RESULTS: Of the 200 surveys that were distributed,
      142 were completed for a response rate of 71%. Of the respondents, 75% reported
      using at least one herb in the last 12 months. Women between 25 and 34 years of
      age were most likely to be herb users (P = .001), while men in that age group
      were the least likely (P = .013). Chamomile (58.5%) and aloe vera (45.3%) were
      used most frequently. Two frequently used herbs--linden (35.8%) and star anise
      (33.0%)--are ones that are generally not well known to health care professionals.
      Family tradition (36%) and safety (17%) were the major reasons for use of
      herb/herbal remedies. Participants most commonly reported spending 25 dollars or
      less per month for herbs and herbal products. CONCLUSION: Hispanics in south
      Florida reported using herbs and herbal products at a higher rate than that those
      reported previously for the general population of the United States. While money
      spent on herbs and herbal products was generally minimal, study participants had
      a disconcerting level of confidence in the safety and efficacy of herbal
      products.

PMID- 16602227
TI  - Pharmacist involvement with immunizations: a decade of professional advancement.
AB  - OBJECTIVE: To review achievements in pharmacist-administered immunizations,
      emphasizing the period 1995 to 2004. DATA SOURCES: Published articles identified
      through PubMed (1995-2004) using the search terms pharmacist, pharmacy, and
      vaccine, immunization, or shots. Additional sources were identified from personal
      bibliographies collected by the authors during this decade, as well as the
      bibliographies of the retrieved articles. The later two sources resulted in
      manuscripts of primarily historical significance. STUDY SELECTION: More than 300
      manuscripts were identified. The authors selected 15 studies that most clearly
      document the effect of pharmacist-administered immunizations for review. DATA
      EXTRACTION: By the authors. DATA SYNTHESIS: While pharmacists have been involved
      with vaccines dating back to the mid-1800s and the distribution of smallpox
      vaccine, only 10 years have passed since pharmacists began routinely immunizing
      patients in their communities as a standard practice activity. The Washington
      State Pharmacists Association initiated the first ongoing formalized training of
      pharmacists in vaccine administration in 1994. On November 1, 1996, the American
      Pharmaceutical (now Pharmacists) Association (APhA) began its nationally
      recognized training program for pharmacists, Pharmacy-Based Immunization
      DELIVERY: A National Certificate Program for Pharmacists. By 2004, an estimated
      15,000 pharmacists and student pharmacists had been formally trained through
      recognized programs as vaccine experts, and the practice of pharmacist
      administered immunizations, particularly for adult patients, has become routinely
      accepted as an important role of the pharmacist. Arguably, few initiatives have
      done more to move the pharmacy profession forward in direct patient care than the
      pharmacist-administered immunization movement. CONCLUSION: Pharmacists have made
      significant strides in immunizations over the past decade. Limited activities in
      the hospital sector have been particularly well documented, as have the
      perceptions of patients regarding acceptance of pharmacists as immunizers. The
      activities of community pharmacists are less well documented. More research is
      needed into novel approaches to pharmacist involvement in public health-focused
      immunization initiatives, along with continued research evaluating the current
      practice of pharmacist-administered immunizations.

PMID- 16602228
TI  - Keeping up-to-date on immunizations: a framework and review for pharmacists.
AB  - OBJECTIVE: To provide a framework for keeping current in the immunizations field;
      an update on changes in adult and pediatric vaccine delivery since 2003; and an
      update on new immunization guidelines, new approved vaccines, and changes in uses
      for current vaccines. DATA SOURCES: Published guidelines identified from the
      Centers for Disease Control National Immunization Program Web site. In addition,
      published articles were identified through Medline (January 2003-November 2005)
      using specific vaccine names as search terms. Additional sources were identified
      from the bibliographies of retrieved articles. STUDY SELECTION: By the authors.
      DATA EXTRACTION: By the authors. DATA SYNTHESIS: To implement the immunization
      services now permitted under law in 44 states, many pharmacists receive initial
      training through the American Pharmacists Association Pharmacy-Based Immunization
      Delivery CERTIFICATE PROGRAM. To remain up-to-date in this field, pharmacists can
      apply the process described in this article, which includes regular monitoring of
      the Web site and publications of the Centers for Disease Control and Prevention
      and participation in one or more listservs. Specific information is presented on
      new vaccines marketed in the United States since 2003 along with updates on
      standards for adult and adolescent immunizations and changes in guidelines during
      this time frame. CONCLUSION: As increasingly committed health professionals in
      the immunizations field, pharmacists are responsible for keeping updated on the
      constantly changing recommendations for vaccines and related products. By
      incorporating the recent information presented in this article and applying the
      process described for tracking changes in this field, pharmacists can fulfill
      their emerging vaccine-related roles on the health care team.

PMID- 16602229
TI  - Follow-on biologics: competition in the biopharmaceutical marketplace.
AB  - OBJECTIVE: To describe the implications of a follow-on biologic approval process
      with focus on current stakeholders, implications of the status quo, and
      recommendations for future policy. DATA SOURCES: A search using Medline,
      International Pharmaceutical Abstracts, Med Ad News, F-D-C Reports/Pink Sheets,
      and Google index directories was conducted with terms such as biologic,
      biopharmaceutical, generic, and follow-on. STUDY SELECTION: Articles pertaining
      to the follow-on biologic debate. DATA EXTRACTION: By the authors. DATA
      SYNTHESIS: Over the past decade, the biopharmaceutical market has experienced
      substantial growth in the number of product approvals and sales. In contrast with
      prescription medications, biologic agents currently lack an abbreviated
      regulatory approval process. Evidence from the Drug Price Competition and Patent
      Term Restoration Act of 1984 suggests that reducing barriers to generic
      competition in the pharmaceutical market successfully increases generic market
      penetration and reduces overall prices to consumers. Although scientific and
      regulatory dissimilarities between biopharmaceuticals and other medications
      exist, a follow-on biologic approval process has the potential to play an
      important role in containing growth in pharmaceutical spending. In addition to
      biopharmaceutical and generic biopharmaceutical manufacturers, stakeholders with
      a vested interest in this debate include individual consumers who continue to
      bear the burden of spending increases in the pharmaceutical market. CONCLUSION:
      The debate over a follow-on process likely will be difficult as parties seek a
      balance between incentives for biopharmaceutical innovation, consumer safety, and
      affordability of existing biologic products.

PMID- 16602230
TI  - Consistent standards in medication use: the need to care for patients from
      research to practice.
AB  - OBJECTIVE: To propose adoption of practice standards for pharmacists based on the
      principles of pharmaceutical care that are parallel to internationally accepted
      ethical precepts governing clinical research. DATA SOURCES: Relevant literature
      selected by the authors. SUMMARY: Pharmaceutical care practice standards can
      create a continuum of high quality care for patients from research through
      practice and are presented as a rational solution to managing the benefits and
      risks of medication use. By implementing these practice standards, patients are
      empowered to become active participants in the treatment process, knowledge of
      drug effectiveness and safety is increased, and the pharmaceutical care
      practitioner's responsibilities are delineated. More than a quarter century ago,
      the research community adopted the ethical principles of respect for persons,
      beneficence, and justice, as outlined in the Belmont Report: Ethical Principles
      and Guidelines for the Protection of Human Subjects of Research. Under these
      guidelines, research subjects are considered participants, knowledge of
      medication efficacy and safety has increased, and investigator responsibilities
      have been defined. However, these guidelines only apply to the life cycle of a
      drug before approval by the Food and Drug Administration. Once the product is
      released for general use, fewer standards are applied. Pharmacy has the
      opportunity to establish parallel standards for the clinical use of medications
      in patients by establishing patient care practices in consonance with
      pharmaceutical care practice. CONCLUSION: Pharmaceutical care practitioners need
      to apply new practice standards that allow them to contribute meaningfully to
      appropriate, effective, safe, and convenient drug therapy for all patients. Such
      pharmaceutical care practice standards could ensure consistent vigilance
      throughout the life cycle of the drug product and result in rational,
      appropriate, effective, safe, and convenient drug therapy for all patients.

PMID- 16602231
TI  - Educating pharmacists on ophthalmic- and otic-drop administration techniques
      using internet-based video clips.

PMID- 16602232
TI  - Impact of pharmacist-provided osteoporosis education and screening in the
      workplace.

PMID- 16602233
TI  - Robert Phillip Fischelis 1891-1981: pharmacy activist.

PMID- 16602234
TI  - Vaccine-adverse event reporting system: an essential tool for monitoring vaccine
      safety.

PMID- 16602235
TI  - New drugs: abatacept, sorafenib, and nelarabine.

PMID- 16602236
TI  - OTC Product: Today Sponge.

PMID- 16602237
TI  - [Endothelium of myocardium microvessel under conditions of hypothermia, ischemia,
      reperfusion and pharmaco-cold cardioplegia with calcium antagonist].
AB  - Microvessels of the right atrium endothelium were investigated with electron
      microscope for patients with congenital heart disease receiving surgical
      treatment under deep perfusionless hypothermia and various methods of pharmaco
      cold cardioplegia. In group 1, pharmaco-cold cardioplegia was performed, with
      hyperosmolar normopotash solution cooled down to 2-4 degrees C. In group 2, the
      same solution combined with isoptin, a potash-ion blocker, was applied. It has
      been shown that during global ischemia, stability of ion gradients on plasmalemma
      of endothelial cells is impaired, irrespective of the composition of cardioplegia
      solution. Alongside with this, ultrastructural reactions in group 1 proceed
      towards hyperosmia of endothelium accompanied by building up a large group of
      cells following coagulation necrosis. In group 2, by contrast, an intracellular
      edema progresses. The cardioprotective effect of isoptin, which is able to block
      Ca2+, manifests itself most vividly at reperfusion, when the blocking of cell
      potash overload prevents the development of dystrophic and destructive changes in
      endothelium of coronary microvessels, which present one of the most severe
      consequences in the process of blood flow recovery in ischemic tissues.

PMID- 16602238
TI  - [Morpho-functional parameters of nucleoli in polyploid mucous and albumen cells
      of salivary gland in the snail Succinea lauta].
AB  - Variation of some characteristics of nucleoli of polyploid mucous and albumen
      cells was examined in salivary glands of the snail Succinea lauta. The number,
      total area and Ag-protein content of nucleoli, and DNA content in each nucleus
      were estimated on squashed preparations incubated with AgNO3, decolorized and
      then Feulgen stained. The ultrastructure of nucleoli was studied by electron
      microscopy. Differentiated mucous cells had 4c-8c-16c-32c nuclei; albumen cells
      had 8c-16c-32c-64c-128c nuclei. The ultrastructure of nucleoli of the two cell
      types was essentially the same. Normally, a large fibrous to granular zone was
      observed in the nucleoli, without a clear distinction between fibrous and
      granular components. At the same time, aggregations of granular matter could be
      discerned at the periphery of nucleoli. No fibrous centers were observed.
      Occassionally, nucleolonema-like structures occurred. Normally each nucleolus
      contacted several chromosomes. On squashed preparations, the least size of
      nucleoli was 2-3 microm, and the largest size amounted to 14 microm in mucous
      cells, and to 50-80 microm in albumen cells. The number of nucleoli rose from 1-2
      in tetraploid nuclei to 2-3 in 32c-nuclei, and to 5-7 in 128c-nuclei. The
      disparity between the ploidy levels of nuclei and the numbers of nucleoli may be
      due, presumably, to aggregation of chromosome NORs. The Ag-protein content in the
      nucleoli, and the total nucleolar area displayed a strong mutual correlation.
      Both parameters differed significantly by 1.5-2.2 times in mucous and albumen
      cells of the same ploidy level. Thus, in albumen and mucous cells the total Ag
      protein content in octaploid nuclei was 3.3 and 2.2 relative units (r. u.),
      respectively. In 16c- and 32c-nuclei of albumen cells, it was 7.6 and 15.1 r. u.;
      and in the same nuclei of mucous cells--3.8 and 6.8 r. u., respectively. On the
      whole, in albumen cells, in the course of 4 endocycles (4c-128c), the total Ag
      protein content increased by 17 times. Therefore, the mean multiplication factor
      for this parameter was found to be 2.05 per endocycle. In mucous cells, in the
      course of 3 endocycles (4c-32c), the total Ag-protein content increased by 5.2
      times against 8 times expected, with the mean multiplication factor equal to 1.75
      per endocycle. Thus, in the course of polyploidization of albumen and mucous cell
      nuclei, the gene dosage effect was fully pronounced in the former, and only
      partly in the latter. This differtence is due obviously to peculiarities of
      differentiation of the two cell types, in particular, to differences in the
      number of activated ribosomal genes.

PMID- 16602239
TI  - [Discovery of a new cellular structure--porosome].
AB  - A new cell structure--"porosome", discovered by the American scientist Bhanu Jena
      and co-wokers, is described. Mechanisms of budding and fusion of transport
      vesicle are elucidated in addition to those of fusion of secretory vesicles at
      the cell plasma membrane, and of release of intravesicular contents. The
      morphology of porosomes, their contents and functional reconstruction in lipid
      bilayer membranes were examined at a near nanometer resolution. Using atomic
      force microscopy, the presence of circular "pits", measuring 400-1200 nm in
      diameter with small 100-150 nm wide "depressions" inside and 3-4 deep pores,
      called porosomes, was demonstrated. A porosome is cup-shaped and 15-30 nm wide.
      Porosomes are the places where secretory vesicles fuse with the plasma cell
      membrane, and where the intravesicular content is released.

PMID- 16602240
TI  - [Il-2-regulated expression of Na+,K(+)-ATPase in activated human lymphocytes].
AB  - Expression of Na+,K(+)-ATPase alfal-subunit and of oubain-sensitive rubidium
      influxes has been investigated in human peripheral blood lymphocytes. Isolated
      lymphocytes were stimulated by phytogemagglutinin (PHA) or interleukin-2 (IL-2).
      It has been shown that during the early stage of the PHA-activation the alfal
      subunit abundance in the membrane fractions of the human blood lymphocytes does
      not change, whereas at the late stages of Go-->G1-->S transition (16-48 h) the
      alfa1 protein content increases. A translation inhibitor cycloheximide was found
      to prevent the late increase in alfa1-subunit expression. An immunosuppressant
      cyclosporin A decreases both IL-2-dependent T-lymphocyte progression and alfa1
      subunit abundance by 48 h of PHA-induced lymphocyte activation. In the
      lymphocytes pretreated by PHA in submitogenic concentration (0.8-1.0 microg/ml)
      exogenous IL-2 (100 U/ml) induces a proliferative response as well as alfal
      protein accumulation. A decrease in alfa1-protein accumulation in the presence of
      specific inhibitors of separate signal transduction pathways enables us to
      conclude that protein kinases ERK1/2 (MAPK pathway) and JAK3 (JAK-STAT pathway)
      mediate the IL-2-dependent regulation of Na+,K(+)-ATPase expression during
      lymphocyte transition from resting stage to proliferation. A correlation between
      changes in ouabain-sensitive rubidium influxes and the alfal-subunit amount has
      been demonstrated. It is concluded that IL-2-dependent-progression of normal
      human lymphocytes from quiescence to proliferation is accompanied by the increase
      in Na+,K(+)-ATPase alfa1-subunits expression, and the enhanced transport activity
      of a sodium pump during the prereplicative stage is provided by the increased
      number of functional pump units in plasma membrane.

PMID- 16602241
TI  - The inductive capacity of proteins secreted by cells of corneal epithelium.
AB  - Two classes of proteins play a leading role in the mechanisms of differentiation.
      The first class presents structural proteins that are fundamental for the
      structure and function of organs. Proteins of the second class are less
      understood; they exist in minor quantities and realize their action only in
      determining the accomplishment by structural proteins of their terminal
      functional state. Here we try to clarify the role of peptides synthesized by the
      corneal epithelium in determining the fate of differentiating cells. The acting
      protein fractions were obtained from isolated corneas of adult pigs, cows and
      carps. Their inducing activities were tested by a standard method, i. e. by
      checking their action on the early gastrula ectoderm of Xenopus laevis. To study
      a possibility of cornea conservation, we used preferentially lyophilizing drying
      of the obtained substances. With some differences in frequency, the protein
      mixtures obtained from all corneas induced the appearance of neural tissue
      (brain), but in the case of lyophilized cow corneas lenses, ear vesicles and
      somites also appeared. The results of this work clearly show the absence of
      homology between the sources of inducing factors and the specificity of their
      action. The cornea is an ectodermal derivative, but its products induce neural
      derivatives and, moreover, after lyophilization they change their induction
      specificity and induce also mesodermal cell types due, presumably, to changes in
      the tertiary structure of protein molecules after lyophilization.

PMID- 16602242
TI  - [Dynamics of spermatogenesis in rabbits Oryctolagus cuniculus].
AB  - The rabbit spermatogenesis was investigated in dynamics with morphology of
      testicular tissues being analysed. Allocation characteristic of spermatogenous
      epithelium cells in spermatic ductules was examined for 19 age groups of rabbit
      males aged from 10 days to 12 months. The availability of three types of
      spermatogonia A, intermediate and B was analysed. In has been determined that the
      age from 10 days to 4 weeks is optimal for isolation of testis stem cells, when
      rabbit spermatogonia are represented by spermatogonia of A-type only.

PMID- 16602243
TI  - [Development of the mammary gland of rabbits].
AB  - Mammogenesis of rabbits was studied in dynamics, including periods of sexual
      maturity (3-6 months old), pregnancy, lactation and involution. A characteristic
      of histological structure of mammary gland of rabbits in different physiological
      periods was done. Variation in maintenance of glandular tissue of mammary gland
      during mammogenesis was analyzed. It has been shown that the share of parenchyma
      tissue is increased with the pregnancy onset and achieves its maximum value by
      the 25-30 th days of pregnancy. The increase in densities of mammocyte nucleus in
      this period and also in the period preceding the sexual maturity was observed
      that is associated with the active proliferation of cells. It is shown that an in
      vitro cell culture, derived during the period preceding the sexual maturity, has
      a great grown potential, whereas a culture devired in the course of lactogenesis
      is characterized by the presence of highly specific lactocytes and has a low
      proliferative activity.

PMID- 16602244
TI  - [Cytotoxic action of polymorphonuclear leukocytes on tumor and normal cells
      during ascite tumor development in vitro and in vivo].
AB  - A vast number of studies, including the authors' own research, support the
      important role polymorphonuclear leukocytes (PMNL) in the development of ascite
      tumors. The method of luminol-dependent chemiluminescence (CL) was used to show
      the presence of two functionally different PMNL pools in a tumor-bearing
      organism: 1) "primed" PMNL, which circulate in the blood stream, and 2)
      "activated" PMNL, which are accumulated in the tumor zone and are capable of
      spontaneous CL. The purpose of the present investigation was to compare cytotoxic
      effects of primed and activated PMNL on tumor cells (ascite Ehrlich carcinoma
      (AEC), ascite Zajdel hepatoma) upon co-cultivation, as well as on normal cells of
      the organism, erythrocytes in vitro and in vivo. Upon stimulation with phorbol
      myristate acetate (PMA), PMNL effectively damaged AEC cells within the first 24 h
      until PMNL apoptosis occurred. Upon further co-cultivation, the tumor cells grew
      in number, which suggest the participation of PMNL in tumor protection. When
      stimulated with PMNL, pools suppressed tumor growth in vitro, since in this case
      the cytotoxicity was due to both reactive oxygen species and proteolytic enzymes.
      As it has been shown earlier by the authors, the functional potential of PMNL
      increases many times during tumor growth, and we suggested that not only tumor
      but also normal cells could be damaged. In this connection, we have studied the
      cytotoxic effect of primed and activated PMNL on rat erythrocytes in vitro on
      their co-cultivation. On stimulation with PMA, the rate of lysis of erythrocytes
      by primed PMNL increase many times compared to the norm. The fMLP-stimulated
      cytotoxity was 1.5-2.0 times higher than in the norm. Activated PMNL without
      stimulation are capable of producing only a partial lysis of erythrocytes (5-7
      %). In order to assess the cytotoxic action of PMNL on erythrocytes in vivo, the
      hemoglobin content in erythrocytes and blood plasm of rats was measured in the
      course of tumor growth. The hemoglobin content in erythocytes during growth tumor
      decreased from 135 +/- 10 to 85 +/- 5 g/l, whereas in the blood plasm the
      hemoglobin content gradually increased by almost two times. The results enable us
      to suggest that one of death causes of tumor-bearing organisms may be the
      cytotoxic action of PMNL on normal cells of the organism caused by
      hyperproduction of ROS.

PMID- 16602245
TI  - [Effect of SWF-radiation on thrombocytes and erythrocyte functions of albino rats
      upon stress condition].
AB  - With the help of a specially designed generator, we have investigated the effect
      of electromagnetic SWF-oscillation, at nitric oxide molecular spectrum of
      radiation and absorption, on the function of thrombocytes and erythrocytes of
      albino rats in the state of immobilizing stress. 5, 15 and 30 min long SWF
      radiation treatments were demonstrated to foster various degrees of restoration
      of thrombocyte and erythrocyte function, the efficiency depending on the period
      of radiation. It was after a 30 min radiation of rats that a most expressed
      restoration of thrombocyte and erythrocyte functional activity was observed.

PMID- 16602246
TI  - [The influence of cooling rates and medium tonicity on Escherichia coli B/r
      survival after heating with different lethal temperatures].
AB  - Cell thermosensitivity of Escherichia coli B/r increases with the cooling rise,
      especially in hypertonic conditions after heating at 50, 55 and 60 degrees C. A
      certain relationship is suggested between the observed phenomenon and the osmotic
      homeostasis system of microorganisms under condition of thermogenic and tonic
      stress.

PMID- 16602247
TI  - [Preparation and characterization of nuclear matrix/chromosome scaffold in situ].
AB  - A method of nuclear matrix and chromosomal scaffold preparation from cultured
      animal cells was developed. After the high-salt extraction, interphase and
      mitotic cells were not detached from the coverslips that enabled us to analyse
      the nuclear matrix and chromosomal scaffold in cells at all mitotic phases.
      Morphological methods (phase contrast microscopy and electron microscopy of
      ultrathin sections) did not reveal any structures that could be identified as a
      chromosomal scaffold. However, after staining with antibodies to XCAP-E and
      topoisomerase IIalpha some structures were revealed in metaphase cells having
      both localization and morphology of a chromosomal scaffold. The cell residuals
      were not stained with antibodies to XCAP-E and topoisomerase IIalpha, if the
      nuclear matrix and chromosomal scaffold were destabilized by addition of beta
      mercaptoethanol.

PMID- 16602248
TI  - [A study of chromosomal fragility in peripheral blood lymphocytes in patients
      with lymphomas].
AB  - Patients with lymphomas were shown to have authentically a higher frequency of
      fragile sites, both spontaneous and induced by aphidikoline expression, in
      comparison with the control group. Differential sensitivity of chromosomes caused
      by the action of aphidikolin was revealed. The fragility of chromosomes 9 and 11
      in patients with lymphomas on sites 9q31-32 and 11p13-14 was authentically higher
      (alpha = 0.05) than that in healthy individuals. Site 9q31-32 appeared to be
      strictly specific for lymphoma disease.

PMID- 16602249
TI  - [Light and electron microscopic investigation of Pelomyxa prima (Gruber, 1884)
      (Peloflagellatea, Pelobiontida)].
AB  - Cell organization of a multinuclear pelobiont Pelomyxa prima has been studied at
      the light and electron microscopic levels. Motile individuals demonstrate a
      characteristic drop-like or pyriform shape and reach 550 microkm in length. The
      cell cover is represented by a well-developed, morphologically differentiated
      glycocalyx 80-100 nm thick. The cytoplasm contains many structural vacuoles. The
      nuclei are of vertical type, numbering up to several nuclei in large individuals.
      Numerous cytoplasmic microtubules are associated with the external membrane of
      the nuclear envelope. Separate non-motile flagella are distributed throughout the
      cell surface, being more numerous in the posterior body end and uroidal zone of
      the protist. Basal bodies of the flagella are extremely long, being deeply
      immersed into the cytoplasm. These bodies are surrounded by a muff of electron
      dense material, with numerous microtubules radiating from it. A compact bundle of
      microtubules starts from the base of a basal body axially into the cytoplasm.
      Besides, a band-like lateral microtubular rootlet is present. The number of
      microtubules in the axoneme of undulipodia is unstable. Neither mitochondria, nor
      Golgi complex were found. Two species of bacterial endocytobionts are present in
      the cytoplasm in considerable numbers.

PMID- 16602250
TI  - The effect of hyperbaric oxygen on intraocular pressure.
AB  - The effects of hyperoxia on intraocular pressure (IOP) have been studied in
      experiments on human beings and animals. The changes occurring in IOP in patients
      during routine HBO2 therapy are unknown. In this study we investigated IOP
      changes arising during the HBO2 therapy at 2.5 ATA. Fifty-six patients receiving
      HBO2 therapy for various reasons were included in the study. Bilateral IOPs of
      patients measured with the Tono-pen XL (Medtronic, Solan, USA) tonometer before,
      during and after HBO2 therapy. Average IOPs were 14.85 +/- 3.17 mmHg (range, 10
      24), 13.00 +/- 2.97 mmHg (range, 9-21) and 14.74 +/- 3.12 mmHg (range, 10-22),
      respectively. IOP was reduced significantly during HBO2 therapy and returned its
      pre- HBO2 levels after therapy. Our data indicated a statistically significant
      decrease in IOPs during therapy at 2.5 ATA. This decrease was of minor
      physiological significance in these patients whose baseline IOP values were
      within the normal range.

PMID- 16602251
TI  - Clinical observation: Beau's lines on fingernails after deep saturation dives.
AB  - Transverse furrows, or Beau's lines, were noted in the fingernails of all 6
      divers following a deep saturation dive to apressure equal to 1100 feet (335
      meters) ofsea water (3,370 kPa), and in 2 of6 divers following a similar dive to
      1000 feet (305 meters) of sea water (3,164 kPa). Both dives took place at the
      Ocean Simulation Facility of the Navy Experimental Diving Unit in Panama City,
      Florida. The divers breathed a partial pressure of 0.40 - 0.44 atm abs (40.5 -
      44.6 kPa) oxygen, with the balance helium, during most of the time under
      pressure. All divers performed hard work on bicycle ergometers during the dives.
      Four of the divers on the first dive were treated during the dive for pain-only
      decompression sickness. Beau's lines have been reported in numerous medical
      conditions such as typhus, rheumatic fever, malaria, myocardial infarction, and
      other severe metabolic stresses. To the author's knowledge this is the first
      report of Beau's lines associated with saturation diving.

PMID- 16602252
TI  - Hypoxemia with air breathing periods in U.S. NAVY Treatment Table 6.
AB  - Air breathing is used to lessen hyperbaric oxygen (HBO2) toxicity. Hypoxemia
      could occur during hyperbaric air breathing in patients with lung dysfunction,
      although this has not been previously reported. We report two cases of hypoxemia
      during air breathing with two patients treated with the US Navy Table 6. Patient
      1 was an 11-year-old male with cerebral gas embolism (during cardiac
      transplantation), patient 2 was a 66-year-old female with cerebral gas embolism
      from a central venous catheter accident. Both were mechanically ventilated. We
      monitored arterial blood gas (ABG) during therapy. In both patients, ABG
      measurements showed hypoxia during the first air breathing period at 1.9 atm abs
      (192.5 kPa). If patients require > or = 40% inspired oxygen before HBO2 therapy,
      oxygenation monitoring is advisable during air breathing periods, especially at
      lower chamber pressures (< or = 2.0 atm abs).

PMID- 16602253
TI  - Wound oxygen levels during hyperbaric oxygen treatment in healing wounds.
AB  - Hyperbaric oxygen (HBO2) increases wound oxygen delivery, but few data quantify
      wound oxygen levels over the course of healing. We characterized these changes
      during and after HBO2 treatment in a rat wound model. The treatment group (n=7)
      received 2.0 ATA HBO2, 90 minutes BID for 15 days. Control rats (n=5) were only
      exposed to HBO2 during measurement. On days 5, 10, and 15, wound pO2 was measured
      before, during, and for an hour after HBO2 treatment. Both the peak pO2 and the
      pO2 one hour after HBO2 treatment were significantly greater than baseline on all
      days in both the treatment (p < .01) and control group (p < .05). The peak pO2
      during HBO2 exposure and one hour after decreased significantly in the treatment
      group on day 15 compared to day 5 (p <.01, p <.05 respectively). No significant
      differences were found in pO2 values between days within the control group. These
      results demonstrate that both the peak wound oxygen levels and duration of
      elevation change significantly throughout the course of HBO2 treatment.

PMID- 16602255
TI  - A pilot study with long term follow up of hyperbaric oxygen pretreatment in
      patients with locally advanced breast cancer undergoing neo-adjuvant
      chemotherapy.
AB  - Work in an animal cancer model suggests that pretreatment with hyperbaric oxygen
      can improve tumor vascularity rendering chemotherapy more effective. Accordingly
      32 subjects with locally advanced breast carcinoma (>5cm diameter) entered into a
      randomized clinical trial where a course was administered of six intravenous
      pulses of cyclophosphamide 1000mg/m2 i.v., doxorubicin 50mg/m2 i.v. and
      vincristine 1.5mg/m2 i.v. In the case group this was preceded by ten, once daily,
      sessions of hyperbaric oxygen therapy (HBO2) administered either at 2.4 or 2.0
      atmospheres absolute. Eleven out of 15 subjects tolerated a full course of HBO2
      and chemotherapy. All 17 control subjects tolerated a full course of
      chemotherapy. Tumor extravascular extracellular or edema fluid was reduced after
      HBO2 but there was no reduction in tumor cell volume and no indication of
      increased vascularity on MRI. Clinical and pathological responses to chemotherapy
      were the same in both groups and there was no evidence of neovascularisation.
      Five year survival in those who tolerated the trial regime was 73% and did not
      differ between the groups. This mortality was cancer related.

PMID- 16602254
TI  - A prospective, randomized clinical trial comparing two hyperbaric treatment
      protocols for carbon monoxide poisoning.
AB  - INTRODUCTION: The optimal hyperbaric oxygen (HBO2) treatment protocol for acute
      carbon monoxide (CO) poisoning is unknown. This is indicated by one study that
      found 18 different protocols to treat CO poisoning by North American multiplace
      hyperbaric facilities. A pilot study was conducted to evaluate the feasibility of
      randomizing patients to different protocols and to determine whether any large
      differences in clinical outcome were present between the two most common
      protocols. METHODS: Adult patients with accidental CO poisoning resulting in
      transient loss of consciousness, presentation to the emergency department within
      12 hours, primary language English, high school education, and residence within
      100 miles of the hyperbaric facility were recruited. Enrolled patients were
      randomized to one HBO2 treatment at 2.4 atmospheres absolute (atm abs) pressure
      with 90 minutes of 100% oxygen breathing vs. treatment by the US Air Force CO
      protocol (3.0 atm abs maximum pressure). A neurocognitive screening test was
      performed immediately after hyperbaric treatment and repeated 14-21 days later.
      RESULTS: From 1995 to 2002, 30 patients age 21 to 88 years were randomized, 18 to
      treatment at 2.4 atm abs and 12 to 3.0 atm abs. Average carboxyhemoglobin level
      for the population was 24.8 +/- 8.8% (mean +/- SD). Delay to hyperbaric treatment
      averaged 313 +/- 129 minutes. Neither variable was different between treatment
      groups. Six patients had abnormal neurocognitive testing immediately following
      hyperbaric treatment, 4 in the 2.4 atm abs group (22%) and 2 in the 3.0 atm abs
      group (17%) (P=0.71). One patient in each group demonstrated abnormality on
      delayed testing (p=0.75). One in each group did not return for follow-up.
      CONCLUSIONS: It is feasible to randomize CO-poisoned patients to different
      hyperbaric treatment protocols. Determination of differences in efficacy between
      treatment protocols will require a large multicenter trial with the use of
      detailed neurocognitive testing.

PMID- 16602256
TI  - Validity of cycle test in air compared to underwater cycling.
AB  - According to international guidelines, fitness to dive is generally assessed
      using a bicycle stress test (BST) in air. To date, there is no study explicitly
      addressing the question whether the results of a BST in air really predict
      performance status under water. Therefore, the aim of the present study was
      twofold: first, to design an experimental setting allowing the examination of
      physical performance status under water, and second, to examine whether there is
      an association of response to exercise in air compared to exercise under water
      using self contained underwater breathing apparatus (SCUBA). We constructed and
      evaluated a measurement technique for a bicycle ergometry and for gas analysis
      under water. Part of the work was the development of a new valve system which
      allowed to collect the exhaled air in total and to transport it to the spirometer
      next to the pool. Twenty-eight healthy male divers underwent a BST. Compared to a
      given workload in air, gross capacity decreased significantly by about 50%
      underwater. High performance in air was associated with a high performance
      underwater. The examinations were carried out without any complications. In
      conclusion, our experimental setting allowed the safe and reliable examination of
      physical performance status under water. First results indicate that the results
      of a BST in air correlate well with the cardio-circulatory performance status
      underwater. A subsequent study with a larger sample size will enable us to more
      precisely model this correlation.

PMID- 16602257
TI  - Adverse events in competitive breath-hold diving.
AB  - Medical observations are reported from an eight-day world championship breath
      hold diving competition involving 57 participants. The deepest dive was to 75
      metres, and the longest breath-hold time exceeded 9 minutes. There were 35 diving
      related adverse events witnessed or reported, including transient loss of motor
      control due to hypoxia, syncope during ascent, hemoptysis, and pulmonary edema.
      All events occurred in healthy individuals, and resolved without apparent
      sequelae. There was no relationship between symptoms and depth. The medical
      implications of these adverse events are discussed. Despite the inherent risks of
      the sport, established organizational procedures for competitive breath-hold
      diving maintain a high degree of safety.

PMID- 16602258
TI  - Effects of 30-m nitrox saturation dive on the immune system in man.
AB  - Hyperbaria reportedly affects the immune system, but the role of psychological
      factors arising from confinement has not been taken into consideration. We
      investigated the immune changes in 4 subjects exposed to a 9-day simulated 30-m
      (400-kPa) nitrogen-oxygen (nitrox) saturation dive, and compared the results with
      those of our previous study that showed immune and mood changes in normobaric
      confinement. Blood samples were taken before, during, and after the dive or
      confinement, and activated with an anti-CD2 agonistic antibody. The percentages
      of granulocytes, natural killer (NK) cells, and cells positive for CD69, an early
      activation marker, were analyzed by flow cytometry. Reduction of CD69 expression
      percentage was observed under both hyperbaric and normobaric conditions.
      Percentages of innate immune cells, such as granulocytes and NK cells decreased
      or remained mostly unchanged, contrasting with our previous study, which
      demonstrated increases in both percentages coordinate with mood improvement. We
      conclude that these changes may have been triggered by suppression of sympathetic
      nerve activity that occurs in 30-m nitrox saturation hyperbaria.

PMID- 16602259
TI  - Disaster myths and hurricane Katrina 2005: can public officals and the media
      learn to provide reponsible crisis communication during disasters?

PMID- 16602260
TI  - Surviving collapsed structure entrapment after earthquakes: a "time-to-rescue"
      analysis.
AB  - INTRODUCTION: Massive earthquakes often cause structures to collapse, trapping
      victims under dense rubble for long periods of time. Commonly, this spurs
      resource intensive, dangerous, and frustrating attempts to find and extricate
      live victims. The search and rescue phase usually is maintained for many days
      beyond the last "save," potentially diverting critical attention and resources
      away from the pressing needs of non-trapped survivors and the devastated
      community. This recurring phenomenon is driven by the often-unanswered question
      "Can anyone still be alive under there?" The maximum survival time in entrapment
      is an important issue for responders, yet little formal research has been
      conducted on this issue. Knowing the maximum survival time in entrapment helps
      responders: (1) decide whether or not they should continue to assign limited
      resources to search and rescue activities; (2) assess the safety risks versus the
      benefits; (3) determine when search and rescue activities no longer are
      indicated; and (4) time and pace the important transition to community recovery
      efforts. METHODS: The time period of 1985-2004 was selected for investigation.
      Medline and Lexis-Nexis databases were searched for earthquake events that
      occurred within this timeframe. Medical literature articles providing time
      torescue data for victims of earthquakes were identified. Lexis-Nexis reports
      were scanned to select those with time-to-rescue data for victims of earthquakes.
      Reports from both databases were examined for information that might contribute
      to prolonged survival of entrapped individuals. RESULTS: A total of 34 different
      earthquake events met study criteria. Forty-eight medical articles containing
      time-to-rescue data were identified. Of these, the longest time to rescue was "13
      19 days" post-event (secondhand data and the author is not specific). The second
      longest time to rescue in the medical articles was 8.7 days (209 hours). Twenty
      five medical articles report multiple rescues that occurred after two days (48
      hours). Media reports describe rescues occurring beyond Day 2 in 18 of 34
      earthquakes. Of these, the longest reliably reported survival is 14 days after
      impact, with the next closest having survived 13 days. The average maximum times
      reported from these 18 earthquakes was 6.8 days (median = 5.75 days). The event
      with the most media reports of distinct rescue events was the 1999 Marmara,
      Turkey earthquake (43 victims). Times range from 0.5 days (12 hours) to 6.2 days
      (146 hours) for this event. Both databases provide little formal data to develop
      detailed insight into factors affecting survivability during entrapment.
      CONCLUSIONS: A thorough search of the English-language medical literature and
      media accounts provides a provocative picture of numerous survivors beyond 48
      hours of entrapment under rubble, with a few successfully enduring entrapment of
      13-14 days. These data are not necessarily applicable to non-earthquake collapsed
      structure events. For incident managers and their medical advisors, the study
      findings and discussion may be useful for post-impact decision-making and in
      establishing and/or revising incident priorities as the response evolves.

PMID- 16602261
TI  - Precision of in-hospital triage in mass-casualty incidents after terror attacks.
AB  - INTRODUCTION: Proper management of mass-casualty incidents (MCIs) relies on
      triage as a critical component of the disaster plan. OBJECTIVE: [corrected] The
      objective of this study was to assess the precision of triage in mass-casualty
      incidents. METHODS: The precision of decisions made by two experienced triage
      officers was examined in two large MCIs. These decisions were compared to the
      real severity of injury as defined by the Israeli Defence Forces (IDF)
      classification of severity of injuries and the Injury Severity Score (ISS).
      RESULTS: Two experienced trauma physicians triaged a total of 94 casualties into
      77 mild, seven moderate, and 10 severe casualties. Based on the IDF criteria,
      there were 74 mild, five moderate, and 15 severe casualties. Based on ISS
      scoring, there were 78 mild (ISS <9), five moderate (9 < or = ISS < 16), and 11
      severe (ISS <16) casualties. Of 15 severely injured victims defined by the IDF
      classification of injury severity, the triage officers identified only seven
      (47%). CONCLUSION: Primary triage, even when carried out by experienced trauma
      physicians, can be unreliable in a MCI.

PMID- 16602262
TI  - Integrated decision-making in response to weapons of mass destruction incidents:
      development and initial evaluation of a course for healthcare professionals.
AB  - INTRODUCTION: Standardized, validated training programs for teaching
      administrative decision-making to healthcare professionals responding to weapons
      of mass destruction (WMD) incidents have not been available. Therefore, a
      multidisciplinary team designed, developed, and offered a four-day, functional
      exercise, competency-based course at a national training center. OBJECTIVE: This
      report provides a description of the development and initial evaluation of the
      course in changing participants' perceptions of their capabilities to respond to
      WMD events. METHODS: Course participants were healthcare professionals, including
      physicians, nurses, emergency medical services administrators, hospital
      administrators, and public health officials. Each course included three modified
      tabletop and/or real-time functional exercises. A total of 441 participants
      attended one of the eight course offerings between March and August 2003. An
      intervention group only, pre-post design was used to evaluate change in perceived
      capabilities related to administrative decision-making for WMD incidents. Paired
      evaluation data were available on 339 participants (81.9%). Self-ratings for each
      of 21 capability statements were compared before and after the course. A 19-item
      total scale score for each participant was calculated from the pre-course and
      post-course evaluations. Paired t-tests on pre- and post-course total scores were
      conducted separately for each course. RESULTS: There was consistent improvement
      in self-rated capabilities after course completion for all 21 capability
      statements. Paired t-tests of pre- and post-course total scale scores indicated a
      significant increase in mean ratings for each course (all p < 0.001). CONCLUSION:
      The tabletop/real-time-exercise format was effective in increasing healthcare
      administrators' self-rated capabilities related to WMD disaster management and
      response. Integrating the competencies into training interventions designed for a
      specific target audience and deploying them into an interactive learning
      environment allowed the competency-based training objectives to be accomplished.

PMID- 16602263
TI  - Enhancing local health department disaster response capacity with rapid community
      needs assessments: validation of a computerized program for binary attribute
      cluster sampling.
AB  - INTRODUCTION: Local health departments are among the first agencies to respond to
      disasters or other mass emergencies. However, they often lack the ability to
      handle large-scale events. Plans including locally developed and deployed tools
      may enhance local response. Simplified cluster sampling methods can be useful in
      assessing community needs after a sudden-onset, short duration event. METHODS:
      Using an adaptation of the methodology used by the World Health Organization
      Expanded Programme on Immunization (EPI), a Microsoft Access-based application
      for two-stage cluster sampling of residential addresses in Louisville/Jefferson
      County Metro, Kentucky was developed. The sampling frame was derived from
      geographically referenced data on residential addresses and political districts
      available through the Louisville/Jefferson County Information Consortium (LOJIC).
      The program randomly selected 30 clusters, defined as election precincts, from
      within the area of interest, and then, randomly selected 10 residential addresses
      from each cluster. The program, called the Rapid Assessment Tools Package (RATP),
      was tested in terms of accuracy and precision using data on a dichotomous
      characteristic of residential addresses available from the local tax assessor
      database. A series of 30 samples were produced and analyzed with respect to their
      precision and accuracy in estimating the prevalence of the study attribute. Point
      estimates with 95% confidence intervals were calculated by determining the
      proportion of the study attribute values in each of the samples and compared with
      the population proportion. To estimate the design effect, corresponding simple
      random samples of 300 addresses were taken after each of the 30 cluster samples.
      RESULTS: The sample proportion fell within +/-10 absolute percentage points of
      the true proportion in 80% of the samples. In 93.3% of the samples, the point
      estimate fell within +/-12.5%, and 96.7% fell within +/-15%. All of the point
      estimates fell within +/-20% of the true proportion. Estimates of the design
      effect ranged from 0.926 to 1.436 (mean = 1.157, median = 1.170) for the 30
      samples. CONCLUSIONS: Although prospective evaluation of its performance in field
      trials or a real emergency is required to confirm its utility, this study
      suggests that the RATP, a locally designed and deployed tool, may provide
      population-based estimates of community needs or the extent of event-related
      consequences that are precise enough to serve as the basis for the initial post
      event decisions regarding relief efforts.

PMID- 16602264
TI  - On-site physicians at a major sporting event in Nigeria.
AB  - INTRODUCTION: Although the need for on-site physicians at mass gatherings has
      been investigated in developed countries, it has not been studied in a developing
      country, where resources are limited, paramedical services are unavailable, and
      transportation and other facilities are inadequate. HYPOTHESIS: The presence of
      on-site physicians would result in the effective management and prehospital care
      of casualties at mass gatherings or major sporting events in a developing
      country. METHODS: A retrospective review of the planning procedures and medical
      records of the 19th Nigerian University games was conducted. Data from
      demographic profiles of visitors presenting to the on-site, secondary, and
      tertiary medical centers and the treatments used were extracted from log-books
      and processed and interpreted. RESULTS: The Games hosted 6000 accredited athletes
      and officials, and an estimated 80,000 spectators. Medical coverage was provided
      by 54 doctors and other healthcare staff at on-site, secondary, and tertiary
      medical centers. No trained paramedics were available. A total of 494 visits were
      made to the medical centers (medical usage rate of 2.1/1000, patient presentation
      rate of 0.08). Forty-six percent of the visitors were evaluated by a physician on
      site. Ninety percent of the visits were managed on-site, while 5% and 3% were
      referred to secondary and tertiary medical centers, respectively. CONCLUSION: The
      presence of on-site physicians at a major sporting event resulted in the majority
      of injuries and complaints being effectively treated on-scene. This reduced the
      number of hospital referrals and saved time and money for treatment.

PMID- 16602265
TI  - Burns assessment team as part of burn disaster response.
AB  - With a huge, climactically hostile catchment area, limited retrieval options and
      finite resources at the only adult burns unit in South Australia, this paper
      discusses the case for the establishment and maintenance of a Burns Assessment
      Team in South Australia. The composition and role of the team and its
      relationship with other retrieval services, the primary care unit, and the
      proposed National Burn Coordinator also are discussed.

PMID- 16602266
TI  - Post-tsunami medical care: health problems encountered in the International
      Committee of the Red Cross Hospital in Banda Aceh, Indonesia.
AB  - INTRODUCTION: When the Tsunami struck Asia on 26 December 2004, Aceh, Indonesia
      suffered more damage than did any other region. After the Tsunami, many
      humanitarian organizations provided aid in Aceh. For example, the International
      Committee of the Red Cross (ICRC), along with the Indonesian and Norwegian Red
      Cross opened a field hospital in Banda Aceh on 16 January 2005. This study
      describes the illnesses seen in the out-patient department/casualty department
      (OPD/CD) of the ICRC hospital nine weeks after the Tsunami. It describes the
      percentage of people seen for problems directly related to the Tsunami, and
      includes a basic screening for depression and post-traumatic stress disorder
      (PTSD). METHODS: A prospective, five-day study was performed from 01-05 March
      2005. Patients registering in the ICRC field hospital in Banda Aceh were
      considered for the study. Data collected included: (1) age; (2) gender; (3)
      diagnosis in the OPD/CD; and (4) whether or not the problem was related directly
      to the Tsunami. Seven basic questions were asked to screen for depression and
      PTSD symptoms. RESULTS: Twelve percent of the problems seen in the OPD/CD nine
      weeks after the Tsunami still were related directly to the Tsunami. Sixty-three
      percent of patients in the study were male. The medical problems included: (1)
      urological (19%); (2) digestive (16%); (3) respiratory (12%); and (4)
      musculoskeletal (12%). Although <2% of patients were diagnosed with a mental
      health problem, 24% had at least four or more of the seven depression/PTSD
      symptoms addressed in the study. CONCLUSIONS: Post-earthquake and post-tsunami
      health problems and medical needs differ from those found in conflict zones.
      After the Tsunami, both surgical and primary healthcare teams were needed. Many
      problems were chronic medical problems, which may be indicative of the lack of
      healthcare infrastructure before the Tsunami. The findings suggest that mental
      health issues must be taken into consideration for future planning. The ethical
      issues of performing research in complex emergencies also need further
      development at the international level.

PMID- 16602267
TI  - Coordination and resource maximization during disaster relief efforts.
AB  - INTRODUCTION: In the aftermath of the Earthquake and Tsunami in Southeast Asia,
      many relief organizations sent medical aid to affected areas. OBJECTIVE: The aim
      of this paper is to examine the mix of healthcare workers resulting from an
      influx of aid to Meulaboh, Indonesia, and how they met local healthcare needs.
      METHODS: Data were collected from the registration center for relief
      organizations in Meulaboh and daily hospital meetings on healthcare needs and
      available workers. RESULTS: Prior to the Tsunami, there were 14 doctors and 120
      nurses in the hospital. By the third week after the Tsunami, there were 21
      surgeons performing 10 surgeries daily, and >20 non-surgical doctors in the 90
      bed hospital. There were <70 nurses available during the month after the Tsunami,
      which was insufficient for the needs of the hospital. In the town of Meulaboh,
      the number of doctors exceeded the number of nurses, while public health workers
      comprised <5% of the healthcare workers. CONCLUSION: An initial disaster
      coordinating agency, formed by the United Nations (UN) in conjunction with
      affected countries, should link actively with relief organizations. This will
      optimize help in meeting local needs, and direct relief to where it is needed
      most.

PMID- 16602268
TI  - Barriers to disaster coordination: health sector coordination in Banda Aceh
      following the South Asia Tsunami.
AB  - Ecological disasters impact large populations every year, and hundreds of
      nongovernmental organizations, thousands of aid workers, and billions of dollars
      are sent in response. Yet, there have been recurring problems with coordination,
      leading to wasted efforts and funds. The humanitarian response to the December
      2004 Earthquake and Tsunami in Asia was one of the largest ever, and coordination
      problems were apparent. The coordination processes and attempts at coordination
      are discussed in this paper. Specific barriers to cooperation are discussed, such
      as weak leadership, the absence of accountability, the lack of credentialing, the
      diverse goals of the responding agencies, and the weaknesses in the coordination
      process itself.

PMID- 16602269
TI  - Team Echo: observations and lessons learned in the recovery phase of the 2004
      Asian tsunami.
AB  - The 26 December 2004 Tsunami resulted in a death toll of >270,000 persons, making
      it the most lethal tsunami in recorded history. This article presents performance
      data observations and the lessons learned by a civilian team dispatched by the
      Australian government to "provide clinical and surgical functions and to make
      public health assessments". The team, prepared and equipped for deployment four
      days after the event, arrived at its destination 13 days after the Tsunami.
      Aspiration pneumonia, tetanus, and extensive soft tissue wounds of the lower
      extremities were the prominent injuries encountered. Surgical techniques had to
      be adapted to work in the austere environment. The lessons learned included: (1)
      the importance of team member selection; (2) strategies for self-sufficiency; (3)
      personnel readiness and health considerations; (4) face-to-face handover; (5)
      coordination and liaison; (6) the characteristics of injuries; (7) the importance
      of protocols for patient discharge and hospital staffing; and (8) requirements
      for interpreter services. Whereas disaster medical relief teams will be required
      in the future, the composition and equipment needs will differ according to the
      nature of the disaster. National teams should be on standby for international
      response.

PMID- 16602270
TI  - Central system of psychosocial support to the Czech victims affected by the
      tsunami in Southeast Asia.
AB  - The tsunami disaster affected several countries in Southeast Asia in December
      2004 and killed or affected many tourists, most of them from Europe. Eight Czech
      citizens died, and about 500 Czechs were seriously mentally traumatized. The
      psychosocial needs of tourists included: (1) protection; (2) treatment; (3)
      safety; (4) relief; (5) psychological first aid; (6) connecting with family
      members; (7) transportation home; (8) information about possible mental reactions
      to trauma; (9) information about the normality of their reaction; (10) procedural
      and environmental orientation; (11) reinforcement of personal competencies; and
      (12) psycho-trauma therapy. The Ministry of Foreign Affairs of the Czech Republic
      was in charge of general emergency management. General coordination of
      psychosocial support was coordinated under the Ministry of Interior of the Czech
      Republic, which is connected to the Central Crisis Staff of the Czech Government.
      The major cooperative partners were: the Ministry of Foreign Affairs, the
      Ministry of Defence, the Ministry of Health, Czech Airlines, psychosocial
      intervention teams of the Czech Republic, and the Czech Association of Clinical
      Psychologists. The main goals of relief workers were: (1) to bring back home the
      maximum number of Czech citizens; (2) to provide relevant information to the
      maximum number of affected Czech citizens; (3) to provide relevant information to
      rescue workers and professionals; and (4) to prepare working psychosocial support
      regional network. Major activities of the Ministry of Interior (psychology
      section) included: (1) establishing a psychological helpline; (2) running a team
      of psychological assistance (assistance in the Czech airports, psychological
      monitoring of tourists, crisis intervention, psychological first aid, assistance
      in the collection of DNA material from relatives); (3) drafting and distributing
      specific information materials (brochures, leaflets, address lists, printed and
      electronic instructions); (4) communicating via the media and advertising, and
      (5) providing analysis and research studies. Central coordination of psychosocial
      support has been found as successful in the first phase after the disaster. The
      plans must be built for preferable cooperation in the psychosocial field in the
      Czech Republic. Better collaborates with journalists must exist in order to
      reduce secondary psycho-trauma. There is a need for intensive international
      cooperation in the psychosocial field and to build the network at the global
      level.

PMID- 16602271
TI  - Response of Thai hospitals to the tsunami disaster.
AB  - The disaster caused by the tsunami of 26 December 2004 was one of the worst that
      medical systems have faced. The aim of this study was to learn about the medical
      response of the Thai hospitals to this disaster and to establish guidelines that
      will help hospitals prepare for future disasters. The Israeli Defense Forces
      (IDF) Home Front Command (HFC) Medical Department sent a research delegation to
      Thai hospitals to study: (1) pre-event hospital preparedness; (2) patient
      evacuation and triage; (3) personnel and equipment reinforcement; (4) modes used
      for alarm and recruitment of hospital personnel; (5) internal reorganization of
      hospitals; and (6) admission, discharge, and secondary transfer (forward
      management) of patients. Thai hospitals were prepared for and drilled for a
      general mass casualty incident (MCI) involving up to 50 casualties. However, a
      control system to measure the success of these drills was not identified, and
      Thai hospitals were not prepared to deal with the unique aspects of a tsunami or
      to receive thousands of victims. Modes of operation differed between provinces.
      In Phang Nga and Krabi, many patients were treated in the field. In Phuket, most
      patients were evacuated early to secondary (district) and tertiary (provincial)
      hospitals. Hospitals recalled staff rapidly and organized the emergency
      department for patient triage, treatment, and transfer if needed. Although
      preparedness was deficient, hospital systems performed well. Disaster management
      should focus on field-based first aid and triage, and rapid evacuation to
      secondary hospitals. Additionally, disaster management should reinforce and rely
      on the existing and well-trusted medical system.

PMID- 16602272
TI  - Dominance in vertebrate broods and litters.
AB  - Drawing on the concepts and theory of dominance in adult vertebrates, this
      article categorizes the relationships of dominance between infant siblings,
      identifies the behavioral mechanisms that give rise to those relationships, and
      proposes a model to explain their evolution. Dominance relationships in avian
      broods can be classified according to the agonistic roles of dominants and
      subordinates as "aggression-submission," "aggression-resistance," "aggression
      aggression," "aggression-avoidance," "rotating dominance," and "flock dominance."
      These relationships differ mainly in the submissiveness/pugnacity of
      subordinates, which is pivotal, and in the specificity/generality of the learning
      processes that underlie them. As in the dominance hierarchies of adult
      vertebrates, agonistic roles are engendered and maintained by several mechanisms,
      including differential fighting ability, assessment, trained winning and losing
      (especially in altricial species), learned individual relationships (especially
      in precocial species), site-specific learning, and probably group-level effects.
      An evolutionary framework in which the species-typical dominance relationship is
      determined by feeding mode, confinement, cost of subordination, and capacity for
      individual recognition, can be extended to mammalian litters and account for the
      aggression-submission and aggression-resistance observed in distinct populations
      of spotted hyenas and the "site-specific dominance" (teat ownership) of some
      pigs, felids, and hyraxes. Little is known about agonism in the litters of other
      mammals or broods of poikilotherms, but some species of fish and crocodilians
      have the potential for dominance among broodmates.

PMID- 16602273
TI  - Female receptivity, embryonic diapause, and superfetation in the European badger
      (Meles meles): implications for the reproductive tactics of males and females.
AB  - The European badger Meles meles is thought to mate throughout the year with two
      mating peaks occurring in late winter/spring and summer/autumn. After mating,
      fertilized ova enter embryonic diapause (delayed implantation) at the blastocyst
      stage, which lasts up to eleven months. Even if mating is successful, however,
      the estrous cycle may continue during embryonic diapause, which suggests that
      female badgers are capable of superfetation (conception during pregnancy). This
      may increase female fitness by facilitating polyandry, and reduce the risk of
      infanticide by resident males through paternity confusion. Detailed understanding
      of female receptivity, specifically the association of superfetation with
      embryonic diapause, may explain field observations of seemingly inconsistent
      reproductive tactics of male badgers with regard to, for instance, whether or not
      they guard mates or defend territories. The combination of embryonic diapause and
      superfetation may occur in other mustelids; if so, the sociobiology of mustelids
      will need reevaluating, and the Mustelidae may prove to be a good model taxon for
      studies of sexual conflict in the reproduction of eutherian mammals.

PMID- 16602274
TI  - Positive interference from contrast media in cardiac troponin I immunoassays.
AB  - Cardiac troponin I (cTnI) has been found to be a sensitive and reliable marker of
      myocardial damage, and elevated levels of cTnI can indicate high risk for acute
      coronary syndrome. To determine how to intervene in possible cases of acute
      coronary syndrome, cTnI levels must be measured by immunoassay. However, cTnI
      immunoassay results are prone to interference from many substances such as
      heparin and common drugs. The contrast media used in the coronary angiography
      might also interfere with results. To explore this possibility, we performed two
      in vivo and two in vitro studies. In the first in vivo study, we evaluated the
      effects of contrast media on cTnI immunoassays by collecting blood samples from
      45 patients undergoing coronary angiography before and after the procedure. We
      used the Opus Magnum immunoassay system to measure cTnI levels. In the second in
      vivo study, we collected 25 blood samples from another group of patients also
      undergoing angiography at various times before and after the procedure to
      determine cTnI values by both the Opus Magnum and ACCESS systems. In the first in
      vitro study, 12 different contrast media were treated as samples to disclose the
      potential interference of measurement in the two assay systems. In the second in
      vitro study, we made sequential dilutions of iopromide (Ultravist; Schering) with
      serum to explore their potential for interfering with the detection of cTnI by
      the Opus Magnum and ACCESS assays. In the first in vivo study using the Opus
      Magnum assay, cTnI concentrations in samples taken after angiography were
      significantly higher at 5 minutes than at 30 minutes, and, at 60 minutes, all
      cTnI concentrations had dropped below the cutoff point. In the second in vivo
      study, we found a substantial difference in detection of cTnI by the Opus Magnum
      and ACCESS assays. All cTnI concentrations checked by ACCESS assay were below the
      cutoff value. In our first in vitro study, the Opus Magnum assay gave false
      positive results for all 12 contrast media; the ACCESS assay gave a positive
      result for only one contrast medium, poppy-seed oil (Lipiodol; Guebert). In our
      second in vitro study, we found that, in the Opus Magnum assay, the more
      concentrated the contrast medium, the higher the cTnI value, but not in the
      ACCESS assay. We conclude that contrast media may cause false-positive results in
      cTnI assays and that, when contrast media are being used for angiography, cTnI
      results, especially those based on samples taken within the first hour of the
      procedure, should be interpreted carefully.

PMID- 16602275
TI  - Transpositional adipofascial flaps for complicated acute finger injries.
AB  - Seven patients who presented with complicated acute finger injuries were treated
      successfully with local transpositional adipofascial flaps. This is a one-stage
      procedure with advantages of simplicity and rapidity. This flap is thin with good
      pliability and provides a very versatile and reliable covering for soft-tissue
      defects of the fingers. Full-thickness skin grafts were applied to the raw
      surface of the adipofascial flaps in all patients. All cases had excellent wound
      healing and restored full range of motion. This procedure facilitates early wound
      healing and early range of motion for finger joints; it also reduces wound pain,
      minimizes scar formation, and eliminates the need for second-stage surgery.

PMID- 16602276
TI  - Effects of antiglaucoma drugs on cellular proliferation in cultured human corneal
      keratocytes.
AB  - The purpose of this study was to investigate the effects of various antiglaucoma
      drugs, including timolol, betaxolol, carteolol, levobunolol, dipivefrin, and
      pilocarpine, on cellular proliferation in cultured human corneal keratocytes.
      Human corneal keratocytes were cultured with RPMI-1640 medium containing 10%
      fetal bovine serum. Antiglaucoma drugs were prepared from original concentrations
      to dilutions of 1/10, 1/100, and 1/1,000. After exposure to drugs for 100
      minutes, cellular proliferation was estimated by [3H]thymidine uptake
      methodology. It was found that cellular proliferation in corneal keratocytes was
      inhibited by only a 1/10 dilution of various drugs including timolol, betaxolol,
      carteolol, levobunolol, dipivefrin, and pilocarpine. The [3H]thymidine uptake
      values were significantly inhibited to 63%, 18%, 87%, 68%, 55%, and 67% by a 1/10
      dilution of the above drugs. However, the cellular proliferation was also
      significantly suppressed by 0.01 mg/mL of benzalkonium chloride preservative. It
      is shown that the inhibition of cellular proliferation by high concentrations of
      antiglaucoma drugs may result from the benzalkonium chloride preservative
      contained in these drugs.

PMID- 16602277
TI  - Operating room costs of laparoscopic cholecystectomy: does surgeon volume matter?
AB  - Very few studies have addressed the issue of surgeon volume on cost savings of
      laparoscopic cholecystectomy (LC) in Asian countries. The objectives of the study
      were to analyze LC operating-room (OR) costs between two study hospitals and to
      examine the effect of surgeon volume on OR costs. Patients diagnosed with
      gallbladder disease who underwent LC in October through December 2002 at two
      acute tertiary-care hospitals were included. Patient demographics and clinical
      information were derived from patient charts. Cost information was obtained from
      purchasing departments or specific cost centers. Three multivariate linear
      regression models were performed to examine the association between surgeon
      volume, cost, and utilization. There were no significant differences in patient
      demographics and disease severity between the two hospitals. Hospital A consumed
      fewer resources than did hospital B (NTdollars 21,674 vs NTdollars 26,417).
      Direct materials cost, direct professional costs, and indirect costs varied
      significantly by study hospital and by surgeon volume. High-volume surgeons
      incurred lower costs and shorter stay as compared with low-volume surgeons.
      Patients who scored in the American Society of Anesthesiologists physical status
      (ASA PS) 3 incurred significantly higher costs and longer hospital stays than did
      patients with ASA PS 1. The present study supports the proposal that hospital
      management and experience of surgeons are of equal importance in maintaining the
      standing of hospitals in competitive positions. In addition to the differences in
      hospital management and surgeon volume, the patient severity of illness also
      needs to be taken into consideration in cost containment.

PMID- 16602278
TI  - Immunoprofiles in malignant peripheral nerve sheath tumor: three case reports and
      literature review.
AB  - Because there are no standardized radiologic and histologic criteria, the
      differential diagnosis of malignant peripheral nerve sheath tumors (MPNSTs) from
      other spindle cell neoplasms poses great challenges for pathologists. Because
      early diagnosis of MPNSTs arising from benign peripheral nerve sheath tumors
      (BPNSTs) means a better prognosis, many immunohistochemical and molecular studies
      have recently emerged. Nevertheless, no gold standard diagnostic criterion is to
      be found in the literature. For example, S-100 protein is widely used in the
      diagnosis of MPNST. Other promising ancillary markers are p53 and Ki-67; however,
      the staining patterns and possible mechanisms of these markers are seldom
      mentioned in the literature. These evoke our interest. Only six cases diagnosed
      as MPNST were retrieved from the archives of the Department of Pathology,
      Kaohsiung Medical University Chung-Ho Memorial Hospital between 1988 and
      September 2005. Clinical files were available for three of them, and we found
      nuances in the immunohistochemistry from these previous reports. Here, we present
      these rare sarcomas and review the literature.

PMID- 16602279
TI  - Polymerase chain reaction identification of a hymenopteran insect in the cornea:
      a case report.
AB  - The type of corneal injuries associated with insect encounters is related to the
      composition of the foreign body. However, previous reports on corneal foreign
      bodies as insects were rarely based on scientific evidence. Here, we report on a
      49-year-old male who was stung in his left eye by an unknown insect. Emergent
      keratotomy was performed to remove the embedded corneal foreign body. The removed
      foreign body was observed under light microscopy, and a fragment of insect was
      suspected. The sample was sent for molecular analysis. The polymerase chain
      reaction product was sequenced, subjected to a BLAST search, and identified as an
      ichneumonoid member of the insect order Hymenoptera.

PMID- 16602280
TI  - Successful treatment of rubral tremor by high-dose trihexyphenidyl: a case
      report.
AB  - A 24-year-old male suffered from acute-onset right-sided hemiparesis, dysarthria,
      and ophthalmoplegia in February 2001. Brain magnetic resonance imaging revealed a
      cavernous angioma with hemorrhage over the left thalamus. Moreover, some
      rhythmic, coarse, low-frequency (2-3 Hz) oscillation over the right wrist and
      elbow was noted 1 month later. Action tremor was more predominant than resting
      tremor. Rubral tremor was diagnosed on the basis of the clinical presentation and
      tremography analysis. Rubral tremor is not unusual, and pharmacotherapy is nearly
      always ineffective in clinical practice. Deep brain stimulation, thalamotomy, and
      pallidotomy are all considered effective according to recent research. However,
      they are either very expensive or invasive, and involve surgical risks. In our
      patient, we tried valproate, clonazepam, and verapamil one after another, but all
      in vain. Finally, titration of trihexyphenidyl provided significant benefit. The
      tremor was successfully controlled by a single high daily dose of trihexyphenidyl
      (38 mg) without severe or uncomfortable side effects. Here, we report a case of
      successful monotherapy of rubral tremor with high-dose trihexyphenidyl.

PMID- 16602281
TI  - Bladder leiomyoma presenting as voiding dysfunction: a case report.
AB  - Mesenchymal tumors of the urinary bladder are rare, and the majority of them are
      malignant. We report a case of leiomyoma of the urinary bladder presenting with
      symptoms of voiding dysfunction. We performed surgical resection of the leiomyoma
      and repair of the bladder. Small capacity of the bladder with right
      vesicoureteral reflux was noted in outpatient department follow-up. A review of
      the relevant literature is also provided.

PMID- 16602282
TI  - Fundamental trade-offs generating the worldwide leaf economics spectrum.
AB  - Recent work has identified a worldwide "economic" spectrum of correlated leaf
      traits that affects global patterns of nutrient cycling and primary productivity
      and that is used to calibrate vegetation-climate models. The correlation patterns
      are displayed by species from the arctic to the tropics and are largely
      independent of growth form or phylogeny. This generality suggests that
      unidentified fundamental constraints control the return of photosynthates on
      investments of nutrients and dry mass in leaves. Using novel graph theoretic
      methods and structural equation modeling, we show that the relationships among
      these variables can best be explained by assuming (1) a necessary trade-off
      between allocation to structural tissues versus liquid phase processes and (2) an
      evolutionary tradeoff between leaf photosynthetic rates, construction costs, and
      leaf longevity.

PMID- 16602283
TI  - Extinction debt of forest plants persists for more than a century following
      habitat fragmentation.
AB  - Following habitat fragmentation individual habitat patches may lose species over
      time as they pay off their "extinction debt." Species with relatively low rates
      of population extinction and colonization ("slow" species) may maintain
      extinction debts for particularly prolonged periods, but few data are available
      to test this prediction. We analyzed two unusually detailed data sets on forest
      plant distributions and land-use history from Lincolnshire, United Kingdom, and
      Vlaams-Brabant, Belgium, to test for an extinction debt in relation to species
      specific extinction and colonization rates. Logistic regression models predicting
      the presence-absence of 36 plant species were first parameterized using data from
      Lincolnshire, where forest cover has been relatively low (approximately 5-8%) for
      the past 1000 years. Consistent with extinction debt theory, for relatively slow
      species (but not fast species) these models systematically underpredicted levels
      of patch occupancy in Vlaams-Brabant, where forest cover was reduced from
      approximately 25% to <10% between 1775 and 1900 (it is presently 6.5%). As a
      consequence, the ability of the Lincolnshire models to predict patch occupancy in
      Vlaams-Brabant was worse for slow than for fast species. Thus, more than a
      century after forest fragmentation reached its current level an extinction debt
      persists for species with low rates of population turnover.

PMID- 16602284
TI  - Long-term change in benthopelagic fish abundance in the abyssal northeast Pacific
      Ocean.
AB  - Food web structure, particularly the relative importance of bottom-up and top
      down control of animal abundances, is poorly known for the Earth's largest
      habitats: the abyssal plains. A unique 15-yr time series of climate,
      productivity, particulate flux, and abundance of primary consumers (primarily
      echinoderms) and secondary consumers (fish) was examined to elucidate the
      response of trophic levels to temporal variation in one another. Towed camera
      sled deployments in the abyssal northeast Pacific (4100 m water depth) showed
      that annual mean numbers of the dominant fish genus (Coryphaenoides spp.) more
      than doubled over the period 1989-2004. Coryphaenoides spp. abundance was
      significantly correlated with total abundance of mobile epibenthic megafauna
      (echinoderms), with changes in fish abundance lagging behind changes in the
      echinoderms. Direct correlations between surface climate and fish abundances, and
      particulate organic carbon (POC) flux and fish abundances, were insignificant,
      which may be related to the varied response of the potential prey taxa to climate
      and POC flux. This study provides a rare opportunity to study the long-term
      dynamics of an unexploited marine fish population and suggests a dominant role
      for bottom-up control in this system.

PMID- 16602285
TI  - Opposite shifts in size at metamorphosis in response to larval and metamorph
      predators.
AB  - Predation risk can cause organisms to alter the timing of life history switch
      points. Theory suggests that increased risk in an early life stage should select
      for switching earlier and smaller, while increased risk in the subsequent stage
      should select for switching later and larger. This framework has frequently been
      applied to metamorphosis in amphibians, with mixed results. Few studies examining
      the effect of larval predation risk on metamorphosis have observed the predicted
      pattern, and no studies, to our knowledge, have examined the effect of increased
      risk during and after metamorphosis on the timing of this switch point. Here we
      examine the effect of larval and post-metamorphic predation risk on metamorphosis
      in the red-eyed treefrog, Agalychnis callidryas. We raised tadpoles in the
      presence or absence of cues from caged water bugs fed larvae and cues from
      spiders fed emerging metamorphs. Water bugs are effective larval predators, while
      spiders are poor larval predators but prey on metamorphs. Furthermore, since
      spiders forage on the water surface it is possible that tadpoles could assess
      future risk from this predator. Predators induced opposite shifts in life
      history. Tadpoles emerged smaller and less developed in response to water bugs,
      but later and larger in response to spiders. Interestingly, predator effects on
      larval duration were not independent; tadpoles delayed emerging in response to
      spiders, but only in the absence of water bugs.

PMID- 16602286
TI  - Carbon allocation to ectomycorrhizal fungi correlates with belowground allocation
      in culture studies.
AB  - Ectomycorrhizal fungi form symbioses with most temperate and boreal tree species,
      but difficulties in measuring carbon allocation to these symbionts have prevented
      the assessment of their importance in forest ecosystems. Here, I surveyed
      allocation patterns in 14 culture studies and five field studies of
      ectomycorrhizal plants. In culture studies, allocation to ectomycorrhizal fungi
      (NPPf) was linearly related to total belowground net primary production (NPPb) by
      the equation NPPf = 41.5% x NPPb - 11.3% (r2 = 0.55, P < 0.001) and ranged from
      1% to 21% of total net primary production. As a percentage of NPP, allocation to
      ectomycorrhizal fungi was highest at lowest plant growth rates and lowest
      nutrient availabilities. Because total belowground allocation can be estimated
      using carbon balance techniques, these relationships should allow ecologists to
      incorporate mycorrhizal fungi into existing ecosystem models. In field studies,
      allocation to ectomycorrhizal fungi ranged from 0% to 22% of total allocation,
      but wide differences in measurement techniques made intercomparisons difficult.
      Techniques such as fungal in-growth cores, root branching-order studies, and
      isotopic analyses could refine our estimates of turnover rates of fine roots,
      mycorrhizae, and extraradical hyphae. Together with ecosystem modeling, such
      techniques could soon provide good estimates of the relative importance of root
      vs. fungal allocation in belowground carbon budgets.

PMID- 16602287
TI  - Microbial community variation and its relationship with nitrogen mineralization
      in historically altered forests.
AB  - Past land use can impart soil legacies that have important implications for
      ecosystem function. Although these legacies have been linked with microbially
      mediated processes, little is known about the long-term influence of land use on
      soil microbial communities themselves. We examined whether historical land use
      affected soil microbial community composition (lipid profiles) and whether
      community composition was related to potential net nitrogen (N) mineralization
      rates in southern Appalachian (USA) forest stands abandoned from agriculture or
      logging and reforested >50 yr ago. Microbial community composition was determined
      by a hybrid procedure of phospholipid fatty acid (PLFA) and fatty acid methyl
      ester (FAME) analysis. We found that community composition varied significantly
      with past land use. Communities in formerly farmed stands had a higher relative
      abundance of markers for gram-negative bacteria and a lower abundance of markers
      for fungi compared with previously logged and reference (i.e., no disturbance
      history) stands. Potential net N mineralization rates were negatively correlated
      with fungal and gram-negative bacterial markers in both farmed and reference
      stands, and fungal abundance and soil bulk density effectively predicted
      mineralization rates in all stands. Our results indicate that the alteration of
      microbial communities by historical land use may influence the ecosystem
      processes they mediate. This is in contrast to typical expectations about
      microbial community resilience to change. Here, the decrease in fungal abundance
      observed from disturbance appeared to result in decreased nitrogen mineralization
      over the long term.

PMID- 16602288
TI  - Ecological consequences of carbon substrate identity and diversity in a
      laboratory study.
AB  - Plants return a wide range of carbon (C) substrates to the soil system. The
      decomposition rate of these substrates is determined by their chemical nature,
      yet few studies have examined the relative ecological role of specific substrates
      (i.e., substrate identity) or mixtures of substrates. Carbon substrate identity
      and diversity may alter soil chemistry and soil community composition, resulting
      in changes in belowground ecosystem functions such as decomposition and nutrient
      transfer, creating feedbacks that may affect plant growth and the aboveground
      community. A laboratory experiment was set up in which eight C substrates of
      varying chemical complexity were added to a base soil singly, in pairs, fours, or
      with all eight together every four days over a 92-day period. After 92 days these
      soils were analyzed for changes in chemistry, microbial community structure, and
      components of ecosystem functioning. The identity of the added C substrates
      significantly affected soil chemistry, microbial basal and substrate-induced
      respiration, and soil microbial community structure measured by either the
      catabolic response profile (CRP) technique or phospholipid fatty acid
      composition. These belowground changes strongly affected the ability of the soil
      microflora to decompose cellulose paper, probably because of differential effects
      of the C substrates on soil energy supplies and enzyme activities. The addition
      of C substrates to soils also reduced plant growth compared to the unamended
      control soil, but less so in soils amended with a tannin than those amended with
      other substrates. Carbon substrate diversity effects saturated at low diversity
      levels, tended to have neutral or negative effects on ecosystem functions, and
      depended strongly on which C substrates were added. It increased CRP compound use
      but had little effect on other measures of the soil microbial community. Overall,
      results showed that the chemical nature of C substrates added to soil, and
      sometimes their diversity, can affect the soil microbial community and soil
      chemistry, which subsequently affect other ecosystem processes such as
      decomposition and plant growth. The identity and diversity of substrates that
      plants add to soil may therefore have important consequences for both above- and
      belowground ecosystem functions.

PMID- 16602289
TI  - Persistence of rock-derived nutrients in the wet tropical forests of La Selva,
      Costa Rica.
AB  - We used strontium isotopes and analysis of foliar and soil nutrients to test
      whether erosion can rejuvenate the supply of rock-derived nutrients in the
      lowland tropical rain forest of La Selva, Costa Rica. We expected that these
      nutrients would be depleted from soils on stable surfaces, a result of over one
      million years of weathering in situ. In fact, trees and palms in all landscape
      positions derive a relatively high percentage (> or =40%) of their strontium from
      bedrock, rather than atmospheric, sources. The fraction that is rock-derived
      increases on slopes, but with no detectable effect on plant macronutrient
      concentrations. These results differ from those in a similar ecosystem on Kauai,
      Hawaii, where plants on uneroded surfaces derive almost all of their foliar Sr
      from atmospheric, rather than bedrock, sources. The results from La Selva
      challenge the assumption that tropical Oxisols in general have low nutrient
      inputs from bedrock, and support the hypothesis that erosion can increase the
      supply of these nutrients in lower landscape positions.

PMID- 16602290
TI  - Bromus tectorum invasion alters nitrogen dynamics in an undisturbed arid
      grassland ecosystem.
AB  - The nonnative annual grass Bromus tectorum has successfully replaced native
      vegetation in many arid and semiarid ecosystems. Initial introductions
      accompanied grazing and agriculture, making it difficult to separate the effects
      of invasion from physical disturbance. This study examined N dynamics in two
      recently invaded, undisturbed vegetation associations (C3 and C4). The response
      of these communities was compared to an invaded/ disturbed grassland. The
      invaded/disturbed communities had higher surface NH4+ input in spring, whereas
      there were no differences for surface input of NO3-. Soil inorganic N was
      dominated by NH4+, but invaded sites had greater subsurface soil NO3-. Invaded
      sites had greater total soil N at the surface four years post-invasion in
      undisturbed communities, but total N was lower in the invaded/disturbed
      communities. Soil delta15N increased with depth in the noninvaded and recently
      invaded communities, whereas the invaded/disturbed communities exhibited the
      opposite pattern. Enriched foliar delta15N values suggest that Bromus assimilated
      subsurface NO3-, whereas the native grasses were restricted to surface N. A
      Rayleigh distillation model accurately described decomposition patterns in the
      noninvaded communities where soil N loss is accompanied by increasing soil
      delta15N; however, the invaded/ disturbed communities exhibited the opposite
      pattern, suggesting redistribution of N within the soil profile. This study
      suggests that invasion has altered the mechanisms driving nitrogen dynamics.
      Bromus litter decomposition and soil NO3- concentrations were greater in the
      invaded communities during periods of ample precipitation, and NO3- leached from
      the surface litter, where it was assimilated by Bromus. The primary source of N
      input in these communities is a biological soil crust that is removed with
      disturbance, and the lack of N input by the biological soil crust did not balance
      N loss, resulting in reduced total N in the invaded/disturbed communities. Bromus
      produced a positive feedback loop by leaching NO3- from decomposing Bromus litter
      to subsurface soil layers, accessing that deepsoil N pool with deep roots and
      returning that N to the surface as biomass and subsequent litter. Lack of new
      inputs combined with continued loss will result in lower total soil N, evidenced
      by the lower total soil N in the invaded/disturbed communities.

PMID- 16602291
TI  - Patterns in soil fertility and root herbivory interact to influence fine-root
      dynamics.
AB  - Fine-scale soil nutrient enrichment typically stimulates root growth, but it may
      also increase root herbivory, resulting in trade-offs for plant species and
      potentially influencing carbon cycling patterns. We used root ingrowth cores to
      investigate the effects of microsite fertility and root herbivory on root biomass
      in an aggrading upland forest in the coastal plain of South Carolina, USA.
      Treatments were randomly assigned to cores from a factorial combination of
      fertilizer and insecticide. Soil, soil fauna, and roots were removed from the
      cores at the end of the experiment (8-9 mo), and roots were separated at harvest
      into three diameter classes. Each diameter class responded differently to
      fertilizer and insecticide treatments. The finest roots (< 1.0 mm diameter),
      which comprised well over half of all root biomass, were the only ones to respond
      significantly to both treatments, increasing when fertilizer and when insecticide
      were added (each P < 0.0001), with maximum biomass found where the treatments
      were combined (interaction term significant, P < 0.001). These results suggest
      that root-feeding insects have a strong influence on root standing crop with
      stronger herbivore impacts on finer roots and within more fertile microsites.
      Thus, increased vulnerability to root herbivory is a potentially significant cost
      of root foraging in nutrient-rich patches.

PMID- 16602292
TI  - Does plant species co-occurrence influence soil mite diversity?
AB  - Few studies have considered whether plant taxa can be used as predictors of
      belowground faunal diversity in natural ecosystems. We examined soil mite (Acari)
      diversity beneath six grass species at the Konza Prairie Biological Station,
      Kansas, USA. We tested the hypotheses that soil mite species richness, abundance,
      and taxonomic diversity are greater (1) beneath grasses in dicultures (different
      species) compared to monocultures (same species), (2) beneath grasses of higher
      resource quality (lower C:N) compared to lower resource quality, and (3) beneath
      heterogeneous mixes of grasses (C3 and C4 grasses growing together) compared to
      homogeneous mixes (C3 or C4 grasses) using natural occurrences of plant species
      as treatments. This study is the first to examine the interaction between above-
      and belowground diversity in a natural setting with species-level resolution of a
      hyper-diverse taxon. Our results indicate that grasses in diculture supported a
      more species and phylogenetically rich soil mite fauna than was observed for
      monocultures and that this relationship was significant at depth but not in the
      upper soil horizon. We noted that mite species richness was not linearly related
      to grass species richness, which suggests that simple extrapolations of soil
      faunal diversity based on plant species inventories may underestimate the
      richness of associated soil mite communities. The distribution of mite size
      classes in dicultures was considerably different than those for monocultures.
      There was no difference in soil mite richness between grass combinations of
      differing resource quality, or resource heterogeneity.

PMID- 16602293
TI  - Local population size in a flightless insect: importance of patch structure
      dependent mortality.
AB  - In spatially heterogeneous systems, utilizing population models to integrate the
      effects of multiple population rates can yield powerful insights into the
      relative importance of the component rates. The relative importance of
      demographic rates and dispersal in shaping the distribution of the western
      tussock moth (Orgyia vetusta) among patches of its host plant was explored using
      stage-structured population models. Tussock moth dispersal occurs passively in
      first-instar larvae and is poor or absent in all other life stages. Spatial
      surveys suggested, however, that moth distribution is not well explained by
      passive dispersal; moth populations were greater on small patches and on isolated
      ones. Further analysis showed that several local demographic rates varied
      significantly with patch characteristics. Two mortality factors in particular may
      explain the observed patterns. First, crawler mortality both increased with patch
      size and was density-dependent. A single-patch difference equation model showed
      mortality related to patch size is strong enough to overcome the homogenizing
      effect of density dependence; greater equilibrium densities were predicted for
      smaller patches. Second, although three rates were found to vary with local patch
      density, only pupal parasitism by a chalcid wasp could potentially account for
      higher moth abundances on isolated patches. A spatially explicit simulation model
      of the multiple-patch system showed that spatial variation in pupal parasitism is
      indeed strong enough to generate such a pattern. These results demonstrate that
      habitat spatial structure can affect multiple population processes
      simultaneously, and even relatively low attack rates imposed on a reproductively
      valuable life stage of the host can have a dominant effect on population
      distribution among habitat patches.

PMID- 16602294
TI  - Negative relationship between dispersal distance and demography in butterfly
      metapopulations.
AB  - Little is known about the connection between demography and dispersal in
      metapopulations. The meta-analysis of the population time series of five
      butterfly species indicated that (meta)population dynamics are driven by density
      dependent factors. Inter-specific comparison reveals a significant inverse
      relationship between population growth rate and the magnitude of dispersal
      distance. As the range of dispersal distances is constrained by the patch system,
      dispersing individuals moving too far away would (probably) get lost. This
      generates selective pressures on individuals with a high dispersal propensity,
      but favors individuals investing more in reproduction and results in a higher
      (meta)population growth rate. From a conservation perspective, individuals from
      (meta)populations and species sacrificing dispersal for the sake of reproductive
      performances are most vulnerable because of their higher sensitivity to
      stochastic events: the temporal variation of growth rate was much higher in the
      two metapopulations where dispersal was limited.

PMID- 16602295
TI  - Detection of density dependence requires density manipulations and calculation of
      lambda.
AB  - To investigate density-dependent population regulation in the perennial
      bunchgrass Bouteloua rigidiseta, we experimentally manipulated density by
      removing adults or adding seeds to replicate quadrats in a natural population for
      three annual intervals. We monitored the adjacent control quadrats for 14 annual
      intervals. We constructed a population projection matrix for each quadrat in each
      interval, calculated lambda, and did a life table response experiment (LTRE)
      analysis. We tested the effects of density upon lambda by comparing experimental
      and control quadrats, and by an analysis of the 15-year observational data set.
      As measured by effects on lambda and on N(t+1/Nt in the experimental treatments,
      negative density dependence was strong: the population was being effectively
      regulated. The relative contributions of different matrix elements to treatment
      effect on lambda differed among years and treatments; overall the pattern was one
      of small contributions by many different life cycle stages. In contrast, density
      dependence could not be detected using only the observational (control quadrats)
      data, even though this data set covered a much longer time span. Nor did
      experimental effects on separate matrix elements reach statistical significance.
      These results suggest that ecologists may fail to detect density dependence when
      it is present if they have only descriptive, not experimental, data, do not have
      data for the entire life cycle, or analyze life cycle components separately.

PMID- 16602296
TI  - Evidence for life history changes in high-altitude populations of three perennial
      forbs.
AB  - Relatively little is known about how the life histories of perennial forb
      species, and especially their lifetime patterns of growth, vary across
      environmental gradients. We used a post hoc approach (herb-chronology) to
      determine plant age and previous growth (width of successive annual rings in
      roots) in three species of perennial forb (two long-lived species [Penstemon
      venustus, Lupinus laxiflorus] and one short-lived [Rudbeckia occidentalis]) along
      a 1000-m altitudinal gradient in the Wallowa Mountains (northeast Oregon, USA).
      Plants from the highest altitude tended to be considerably older and produced up
      to five times as many flowering shoots as lowland plants. In addition, mean ring
      widths of high-altitude plants were about half those of lowland plants. In plants
      from low and intermediate altitudes, ring width either decreased linearly or
      varied inconsistently during the life of the plant. In contrast, ring widths of
      high-altitude plants increased at first and later decreased, resulting in
      curvilinear growth trajectories that were highly consistent among species.
      Together, these data for three ecologically distinct forb species provide
      evidence of a consistent shift toward more conservative and strongly constrained
      life histories at higher altitudes. More generally, the results indicate the
      possible importance of changes in selection pressures across strong environmental
      gradients on life history strategies within a single species.

PMID- 16602297
TI  - Environmental variation mediates the deleterious effects of Coleosporium ipomoeae
      on Ipomoea purpurea.
AB  - Variation in the environment is common within and between natural populations and
      may influence selection on plant resistance by altering the level of damage or
      the fitness consequences of damage from plant enemies. While much is known about
      how environmental variation influences the amount of damage a plant experiences,
      few studies have attempted to determine how variation in the environment may
      alter the fitness consequences of damage, particularly in plant-pathogen
      interactions. In this work we manipulated a rust pathogen, Coleosporium ipomoeae,
      in field experiments and showed that this pathogen reduced several components of
      fitness in its natural host plant, Ipomoea purpurea. Furthermore, we showed that
      the deleterious effects of C. ipomoeae were variable. We identified variation in
      the quality of a plant's microenvironment, the abundance of secondary enemy
      damage, and the length of a growing season as variable components of the
      environment that may influence the magnitude of damage and tolerance, causing the
      interaction between C. ipomoeae and I. purpurea to vary from parasitism to
      commensalism. Considering how environmental variation impacts the magnitude and
      negative fitness effects of pathogen damage is important to understanding
      spatially variable selection and coevolution in this and other plant-pathogen
      interactions.

PMID- 16602298
TI  - Gastropod herbivory in response to elevated CO2 and N addition impacts plant
      community composition.
AB  - In this study, the influence of elevated carbon dioxide (CO2) and nitrogen (N)
      deposition on gastropod herbivory was investigated for six annual species in a
      California annual grassland community. These experimentally simulated global
      changes increased availability of important resources for plant growth, leading
      to the hypothesis that species with the most positive growth and foliar nutrient
      responses would experience the greatest increase in herbivory. Counter to the
      expectations, shifts in tissue N and growth rates caused by N deposition did not
      predict shifts in herbivore consumption rates. N deposition increased seedling N
      concentrations and growth rates but did not increase herbivore consumption
      overall, or for any individual species. Elevated CO2 did not influence growth
      rates nor have a statistically significant influence on seedling N
      concentrations. Elevated CO2 at ambient N levels caused a decline in the number
      of seedlings consumed, but the interaction between CO2 and N addition differed
      among species. The results of this study indicate that shifting patterns of
      herbivory will likely influence species composition as environmental conditions
      change in the future; however, a simple trade-off between shifting growth rates
      and palatability is not evident.

PMID- 16602299
TI  - Invasion in a diversity hotspot: exotic cover and native richness in the
      Californian serpentine flora.
AB  - Exotic species have been observed to be more prevalent in sites where the
      richness of native species is highest, possibly reflecting variation among sites
      in resources, propagule supply, heterogeneity, or disturbance. However, such a
      pattern leaves unclear whether natives at species-rich sites are subject to
      especially severe impacts from exotics as a result. We considered this question
      using path models in which relationships between exotic cover and native richness
      were evaluated in the presence of correlated environmental factors. At 109 sites
      on serpentine soils across California, USA, exotic cover was positively
      correlated with total native herbaceous richness and was negatively correlated
      with the richness of both serpentine-endemic and rare native herbs. However, in
      path models that accounted for the influences of soil chemistry, disturbance,
      overstory cover, and regional rainfall and elevation, we found no indication that
      exotic cover reduced any component of native herb richness. Rather, our results
      indicated similarities and differences in the conditions favoring exotic, native,
      endemic, and rare species. Our results suggest that, in spite of some localized
      impacts, exotic species are not exerting a detectable overall effect on the
      community richness of the unique native flora of Californian serpentine.

PMID- 16602300
TI  - Flood-pulse and riverscape dynamics in a braided glacial river.
AB  - River ecosystems are increasingly viewed as dynamic riverscapes; their extent,
      composition, and configuration vary in response to the pulsing of discharge.
      Although compositional and configurational shifts in riverscapes are thought to
      control ecosystem processes and biodiversity, attempts to quantify riverscape
      dynamics of braided rivers are scarce. We measured monthly changes in the length,
      spatial arrangement, and age distribution of clear (groundwater-fed) and turbid
      water (glacial-fed) channels during two annual cycles in a braided glacial river.
      Biological data from concurrent studies were used to assess the effects of
      seasonal changes in the size and pattern of the riverscape on local zoobenthic
      density, standing crop of epilithic algae, and spatiotemporal distribution of the
      hyporheos. The hydrological processes involved in the expansion-contraction cycle
      of the riverscape resulted in a complex, albeit predictable, pattern of change in
      the proportion and spatial arrangement of clear and turbid channels. On average,
      30% of the riverscape was renewed at monthly intervals. Surface hydrological
      connectivity and the length of turbid channels increased logarithmically with
      increasing discharge. The length of clear channels increased up to a threshold
      discharge of 1.5 m3/s, above which surface flooding resulted in the contraction
      and fragmentation of clear water bodies. Turbid channels exhibited a unimodal age
      distribution, whereas clear channels had two cohorts that appeared during the
      expansion and contraction phases. The renewal pattern and configuration of the
      riverscape changed little between years despite differences in discharge and the
      occurrence of several rainfall-induced spates. The density of benthic
      invertebrate communities in the main channel decreased with increasing size of
      aquatic habitats indicating that local zoobenthic density was affected by
      dilution-concentration effects. The disproportionate increase in the proportion
      of glacial-fed habitats during summer high flows limited the standing crop of
      epilithic algae in this braided river. The spatial arrangement of inhospitable
      glacial-fed habitats probably impeded the colonization of newly created suitable
      habitats by invertebrates with poor dispersal capacities. Quantification of
      riverscape dynamics is critical to understanding how changes in size,
      composition, and configuration of braided rivers affect biodiversity,
      bioproduction, and ecosystem processes.

PMID- 16602301
TI  - Local extinction of a foundation species in a hypoxic estuary: integrating
      individuals to ecosystem.
AB  - We integrated across individual, population, community, and ecosystem levels to
      understand the impact of environmental stress by tracking the foundation species
      Mytilus edulis in the hypoxic estuary Narragansett Bay, Rhode Island, USA. Our
      initial surveys revealed that the mussels occurred in nine extensive (2-28 ha)
      dense (814-9943 individuals/m2) subtidal reefs that attracted a diverse suite of
      predators (sea stars, crabs, gastropods). Hypoxia occurred in the summer of 2001,
      and a mussel transplant experiment revealed overall reduced growth rates of
      individuals, and higher mortality rates among larger mussels. At the population
      level, large decreases in densities and cover of mussels were correlated with
      dissolved oxygen concentrations, leading to extinction at one site and reductions
      of over an order of magnitude at others. Within one year, seven of the eight
      remaining populations were edged to extinction, and the previously extinct
      population was recolonized. At the community level, a predator exclusion
      experiment indicated that predation was an unimportant source of mussel mortality
      during the hypoxic period, in part due to the emigration of sea stars, as
      predicted by the Consumer Stress Model. However, mussels were too intolerant to
      hypoxia to have a net benefit from the predation refuge. The seasonal (summer)
      occurrence of hypoxia allowed sea stars to return following a lag, as predicted
      by a stress return time model, and the resumption of predation contributed to the
      subsequent extinction of mussel populations. At the ecosystem level, the initial
      filtration rate of the mussel reefs was estimated at 134.6 x 10(6) m3/d,
      equivalent to filtering the volume of the bay 1.3 times during the 26-d average
      residence time. That function was reduced by >75% following hypoxia. The effect
      of hypoxia on each level of organization had consequences at others. For example,
      size-specific mortality and decreased growth of individuals, and reduced
      filtration capacity of reefs, indicated a loss of the ability of mussels to
      entrain planktonic productivity and potential to control future eutrophication
      and hypoxia. Our study quantified patterns of loss and identified pathways within
      an integrative framework of feedbacks, summarized in a conceptual model that is
      applicable to similar foundation species subjected to environmental stress.

PMID- 16602302
TI  - Seascape-dependent subtidal-intertidal trophic linkages.
AB  - In this study, we test in southern New Zealand a conceptual model of food web
      linkage that is seascape dependent, which can explain some of the variability in
      rocky shore community structure among sites and coasts. Using a comparative
      experimental approach at local and distant sites we demonstrate that mobile
      subtidal predators (fish and crabs) can exert strong predation pressure on small
      mussels in the low tidal zone, but only in sites where the seascape includes
      subtidal reefs. On intertidal benches with adjacent subtidal reefs (+SR), 60-100%
      of small (5-15 mm) transplanted mussels were removed within a day from
      experimental tiles on the low shore when unprotected from predation, compared to
      fully caged controls that had approximately 100% survival over several months. In
      partial cages that exclude fish but not crabs, survivorship was intermediate. In
      contrast, on benches without subtidal reefs (-SR) 40-100% of mussels survived for
      months, even if unprotected. This difference is expressed in lower cover (0-60%)
      of mussels on rocks at +SR benches compared to -SR benches (70-99%). The central
      to northern west coast of the South Island is composed mostly of -SR benches, and
      predation on small mussels there was low and similar to the -SR benches on the
      east coast, whereas the +SR benches on the east coast had much greater predation.
      This contrasts to other studies in New Zealand that examined only predation on
      larger mussels by seastars and concluded that predation is strong on the west
      coast and weak on the east coast. Excluding large predators from low-shore areas
      with new recruits for a year in one +SR site showed longer-term predation effects
      on their abundance and cover. Short-term sampling at the east coast sites showed
      that mussel settlement was greater in -SR compared to +SR sites, providing some
      evidence that seascapes may also affect settlement. Overall, predation depended
      on the local seascape and ultimately affected community structure via suppression
      of effective recruitment rates. This study emphasizes the importance of predation
      on early life stages of basal species and the influence of seascapes on top-down
      interactions between subtidal predators and their intertidal prey.

PMID- 16602303
TI  - The length of growing season and adult sex ratio affect sexual size dimorphism in
      moose.
AB  - While factors affecting body growth have been extensively studied, very little is
      known about the factors likely to affect the sexual size dimorphism (SSD) in
      polygynous mammals. Based on the carcass mass of 24420 male and female moose
      recorded in 14 Norwegian populations, we examine three hypotheses to explain
      geographical variation in SSD. First, SSD is expected to decrease when the
      relative density of animals (for a given habitat quality) increases, because
      resource limitation at high population densities is assumed to affect body growth
      of males more than females. Second, because males are selected to invest in
      growth more than females, environmental seasonality and related improvement of
      the forage quality during the short and intense growing season are expected to
      increase SSD. Third, by decreasing the proportion of adult males in the
      population, resulting in start of rutting earlier in life, hunting may decrease
      the SSD by increasing the reproductive cost of young males. We found that males
      grew faster and for a longer time of their life than did females and thus were
      heavier (-24%) when they reached adulthood. Sexual size dimorphism was
      independent of density but was higher in areas with short growing seasons. The
      low SSD in populations with largely adult female-biased sex ratios (males per
      female) shows that male body growth decreases with a decreasing proportion of
      adult males in the population. Our results indicate that geographical variation
      in moose SSD is influenced by divergent responses in the sexes to ecological
      factors affecting body growth.

PMID- 16602304
TI  - Tests of landscape influence: nest predation and brood parasitism in fragmented
      ecosystems.
AB  - The effects of landscape fragmentation on nest predation and brood parasitism,
      the two primary causes of avian reproductive failure, have been difficult to
      generalize across landscapes, yet few studies have clearly considered the context
      and spatial scale of fragmentation. Working in two river systems fragmented by
      agricultural and rural-housing development, we tracked nesting success and brood
      parasitism in > 2500 bird nests in 38 patches of deciduous riparian woodland.
      Patches on both river systems were embedded in one of two local contexts
      (buffered from agriculture by coniferous forest, or adjacent to agriculture), but
      the abundance of agriculture and human habitation within 1 km of each patch was
      highly variable. We examined evidence for three models of landscape effects on
      nest predation based on (1) the relative importance of generalist agricultural
      nest predators, (2) predators associated with the natural habitats typically
      removed by agricultural development, or (3) an additive combination of these two
      predator communities. We found strong support for an additive predation model in
      which landscape features affect nest predation differently at different spatial
      scales. Riparian habitat with forest buffers had higher nest predation rates than
      sites adjacent to agriculture, but nest predation also increased with increasing
      agriculture in the larger landscape surrounding each site. These results suggest
      that predators living in remnant woodland buffers, as well as generalist nest
      predators associated with agriculture, affect nest predation rates, but they
      appear to respond at different spatial scales. Brood parasitism, in contrast, was
      unrelated to agricultural abundance on the landscape, but showed a strong
      nonlinear relationship with farm and house density, indicating a critical point
      at which increased human habitat causes increased brood parasitism. Accurate
      predictions regarding landscape effects on nest predation and brood parasitism
      will require an increased appreciation of the multiple scales at which landscape
      components influence predator and parasite behavior.

PMID- 16602305
TI  - Ecological opportunity and phenotypic plasticity interact to promote character
      displacement and species coexistence.
AB  - We investigated the roles of resource availability and phenotypic plasticity in
      promoting ecological character displacement (i.e., trait evolution stemming from
      resource competition between species). Because ecological character displacement
      generates new populations that differ in resource use, this process should only
      occur when exploitable resources are available. We tested this hypothesis in two
      species of spadefoot toads (Spea bombifrons and S. multiplicata) whose tadpoles
      use phenotypic plasticity to develop into either an omnivore morph, which
      specializes on detritus, or a physically distinctive carnivore morph, which
      specializes on shrimp. Both species grow best on shrimp, but when reared
      together, S. bombifrons outcompetes S. multiplicata for shrimp and S.
      multiplicata outcompetes S. bombifrons for detritus. We found that when each
      species occurred alone in the field, they produced similar proportions of
      omnivores and carnivores. When the two species occurred together, however, they
      underwent ecological character displacement in larval development, with S.
      multiplicata producing mostly omnivores, and S. bombifrons producing mostly
      carnivores. We combined observations of natural populations with experiments to
      evaluate whether such character displacement was only possible when both shrimp
      and detritus were relatively abundant. Mixed-species ponds contained abundant
      detritus and shrimp, in contrast with nearby pure-species ponds, which were
      deficient in one resource. Experiments revealed that S. multiplicata competed
      poorly when detritus was rare and that S. bombifrons competed poorly when shrimp
      was rare. In nature, when one of these two resources was scarce, one species was
      missing, perhaps through competitive exclusion by the species that was the
      superior competitor for the remaining resource. Thus, ecological character
      displacement and, therefore, coexistence of close competitors, was only possible
      when diverse resources were available. Finally, even if exploitable resources are
      available, character displacement is not guaranteed to transpire if species
      cannot utilize such resources expeditiously. Phenotypic plasticity provides a
      general and important mechanism for facilitating resource partitioning. Thus, by
      facilitating shifts in resource use, phenotypic plasticity and ecological
      opportunity may often interact to promote divergence and coexistence of
      competitors.

PMID- 16602306
TI  - Novel features of an inducible defense system in larval tree frogs (Hyla
      chrysoscelis).
AB  - Organisms in aquatic ecosystems must often tolerate variable environmental
      conditions, including an uncertain risk of predation. Individuals that can
      maintain plastic defenses against predation will increase their survival when
      predators are present, but will not incur the costs of these defenses when the
      risk of predation is low and the defense is not induced. Larvae of the pond
      breeding anuran Hyla chrysoscelis develop a conspicuous phenotype in the presence
      of predators consisting of a brightly colored tail and a deeper tail fin. In this
      study, I attempted to identify the source of the chemical signal that induces
      this defensive morphology in this species. I tested whether metabolites alone,
      originating from the prey but passing through the predator, were able to induce
      the same morphological response as the combination of alarm signals released
      directly by attacked conspecifics, and metabolites. I used morphometric and tail
      conspicuousness data to assess tadpole response to the perceived risk of
      predation by larval odonate predators (Anax junius). I also tested whether this
      inducing cue could be recognized across species by measuring the morphological
      response of H. chrysoscelis tadpoles exposed to cues emitted when tadpoles of a
      closely related genus (Pseudacris crucifer) were consumed. Tadpoles exhibited a
      clean graded response of both overall shape and tail morphology in response to
      all cues, corresponding to their relative reliability as indicators of a risk of
      predation. H. chrysoscelis tadpoles were also able to respond to cues emitted
      when tadpoles of a closely related genus were consumed by predators. These
      results illustrate that tadpoles of this species are able to respond to
      metabolites alone without alarm signals, and that interspecific chemical
      communication is a primary mechanism for predator avoidance in this inducible
      defense system.

PMID- 16602307
TI  - Sexual dimorphism in Bosmina: the role of morphology, drag, and swimming.
AB  - Some Bosmina water flea species develop morphological antipredatory defenses,
      such as long antennules and a high carapace, but in Bosmina (Eubosmina) coregoni
      gibbera these traits are larger and more variable in females than in males. Here
      we propose that this sexual dimorphism derives from differential costs of
      hydrodynamic drag and selection for mobility in males. We tested this hypothesis
      by estimating drag of several Bosmina morphologies by using scale models sinking
      in glycerin of different concentrations and viscosities. Body forms included
      males, sexual and asexual females of B. c. gibbera, and males and asexual females
      of Bosmina (Eubosmina) longispina, a taxon with less variable body shape. For a
      given body length or body volume, male models had lower drag than models of
      sexual and asexual females, suggesting that males can swim 14-28% faster with the
      same energy consumption. Consistent with this conclusion, video recordings showed
      that males of B. c. gibbera advanced 55-73% farther than females in each swimming
      stroke. We conclude that hydrodynamic drag may have significant implications for
      swimming and evolution of sexual dimorphism in water fleas, and we suggest that
      males lack the defensive structures of females of B. c. gibbera (e.g., high
      carapaces) because competition over mates favors low drag.

PMID- 16602308
TI  - A new analysis for laser thermal keratoplasty using a focused laser.

PMID- 16602309
TI  - Idiopathic ectasia after LASIK.

PMID- 16602310
TI  - Comparison of higher order aberrations and contrast sensitivity after LASIK,
      Verisyse phakic IOL, and Array multifocal IOL.
AB  - PURPOSE: To evaluate higher order aberrations and contrast sensitivity after
      LASIK, implantation of the Verisyse phakic intraocular lens (IOL), and refractive
      lens exchange with the Array multifocal IOL. METHODS: In a prospective, non
      randomized case series, LASIK was performed in 20 eyes with the Technolas 217z
      excimer laser (Bausch & Lomb, Rochester, NY), a Verisyse phakic IOL (AMO Inc,
      Santa Ana, Calif) was implanted in 11 eyes, and refractive lens exchange with
      implantation of a multifocal IOL (Array IOL, AMO Inc) was performed in 12 eyes.
      Wavefront error (Zywave aberrometer; Bausch & Lomb) at two pupil sizes (4 and 6
      mm) and photopic contrast sensitivity (CVS-1000) was measured preoperatively and
      2 months postoperatively in all eyes. RESULTS: Photopic contrast sensitivity
      remained unchanged in the LASIK and the Verisyse groups, and decrease was
      significant in the Array group at three cycles per degree only. Higher order
      aberrations with a 4-mm pupil were increased in the Array group only. With a 6-mm
      pupil, they were increased in all groups. Comparing groups, surgically induced
      higher order aberrations were highest after refractive lens exchange with the
      Array multifocal IOL and lowest after implantation of the Verisyse IOL.
      CONCLUSIONS: Laser in situ keratomileusis, the Verisyse IOL, and the Array IOL
      increase higher order aberrations at large pupil sizes, but no increase occurs at
      small pupil sizes with LASIK or the Verisyse IOL. Contrast sensitivity in
      photopic conditions is normal with LASIK and the Verisyse IOL, but slightly
      reduced with the Array IOL due to the multifocal optic.

PMID- 16602311
TI  - Wavefront aberrations in eyes with Acrysof monofocal intraocular lenses.
AB  - PURPOSE: To characterize and measure the ocular aberrations in eyes implanted
      with monofocal intraocular lenses (IOLs) and to study any correlation between
      postoperative aberrations and surgical factors. METHODS: A Tscherning aberroscope
      was used to measure the wavefront aberrations of 62 eyes that had undergone
      phacoemulsification with the implantation of foldable monofocal Acrysof MA60BM
      IOLs (Alcon Laboratories Inc, Ft Worth, Tex). The Zernike coefficients, measured
      with a pupil diameter of 6 mm, were compared with those of a normal dataset of 82
      eyes of healthy young myopes. RESULTS: Spherical aberration (Z(0)4) was the most
      predominant higher order aberration, with a mean value of 0.37 +/- 0.16 microm. A
      statistically significant linear relationship was noted between the magnitude of
      postoperative spherical aberration and the dioptric power of the IOL. The mean
      spherical aberration was 33 times more in the pseudophakic group than in normal
      young myopic eyes. The other major higher order aberrations were trefoil (Z(-3)3)
      with a mean of -0.13 +/- 0.22 microm and vertical coma (Z(-1)3) with a mean value
      of -0.11 +/- 0.23 microm. On average, the root-mean-square of higher order
      aberrations in pseudophakic eyes was 2.1 times that in a normal population of
      young myopic eyes. CONCLUSIONS: Eyes that undergo cataract surgery with monofocal
      IOL implantation suffer from significant higher order aberrations. The optical
      design of the IOL is most likely responsible for the increase in spherical
      aberration, the magnitude of which is a function of the dioptric power of the
      IOL.

PMID- 16602312
TI  - Scheimpflug biometry of the anterior segment after implantation of foldable iris
      fixated lenses.
AB  - PURPOSE: To evaluate intraocular dimensions of the anterior segment of myopic
      phakic eyes after implantation of foldable iris-fixated lenses. METHODS:
      Seventeen myopic eyes that received a foldable iris-fixated phakic intraocular
      lens (PIOL) were assessed. Distances between the cornea and the IOL-optic edge
      and between the IOL optic and the crystalline lens were evaluated using
      Scheimpflug photography 3 months postoperatively. RESULTS: The average
      postoperative distance between the central corneal endothelium and the anterior
      surface of the IOL was 2.01 +/- 0.26 mm. The distance between the corneal
      endothelium and the peripheral edge of the IOL averaged 1.32 +/- 0.18 mm at the
      12 o'clock position and 1.34 +/- 0.21 mm at the 6 o'clock position. The distance
      between the crystalline lens and the posterior surface of the IOL averaged 0.73
      +/- 0.09 mm. CONCLUSIONS: The high quality of the three-dimensional Scheimpflug
      images allowed measurements of intraocular distances in PIOL implanted eyes.
      Distances between the foldable iris-fixated IOL and crucial surrounding tissues
      could be determined 3 months postoperatively.

PMID- 16602313
TI  - Retinal detachment in myopic eyes after phakic intraocular lens implantation.
AB  - PURPOSE: To analyze the risk of retinal detachment in highly myopic patients who
      underwent implantation of phakic intraocular lenses (PIOLs). METHODS: In a
      retrospective, non-comparative, interventional case series, the occurrence of
      retinal detachment was analyzed in 522 consecutive highly myopic eyes (323
      patients) that underwent PIOL implantation. Treatment and results were reviewed.
      Parameters evaluated were best corrected visual acuity before and after retinal
      detachment surgery and time between refractive surgery and retinal detachment.
      RESULTS: Fifteen (2.87%) eyes presented with retinal detachment after PIOL
      implantation, with a mean time between surgery and detachment of 24.4 +/- 24.4
      months (range: 1 to 92 months). The risk of retinal detachment in patients with
      high myopia corrected by PIOL implantation was 0.57% at 3 months, 1.64% at 12
      months, 2.73% at 36 months, and 4.06% at 92 to 145 months (Kaplan-Meier
      analysis). A comparative study between the group of patients with retinal
      detachment and the remaining patients without retinal detachment was performed.
      Differences were found in axial length (30.65 +/- 1.97 vs 29.51 +/- 2.02; P=.028,
      one factor-analysis of variance test). CONCLUSIONS: The risk of retinal
      detachment in eyes implanted with phakic lenses for the correction of high myopia
      is higher in eyes with axial length >30.24 mm.

PMID- 16602314
TI  - Laser subepithelial keratomileusis for the correction of high myopia with the
      Schwind ESIRIS scanning spot laser.
AB  - PURPOSE: To investigate the efficacy of laser subepithelial keratomileusis
      (LASEK) for the correction of high myopia with the Schwind ESIRIS scanning spot
      laser (Schwind eye-tech-solutions Gmbh & Co, Kleinostheim, Germany). METHODS:
      Fifty-one patients (76 eyes) were treated with a mean preoperative spherical
      equivalent refraction of -7.55 diopters (D) (range: -6.0 to -10.75 D). All eyes
      received a LASEK technique using 15% alcohol with a 20-second application.
      RESULTS: An intact epithelial flap was obtained in 73 (96%) eyes. At 1 week,
      uncorrected visual acuity (UCVA) was > or =20/30 in 53 (70%) eyes and > or =20/60
      in all eyes. At 6 months (n=76), the mean SE was +0.08 D (range: -1.00 to +1.875
      D) with 73 (96%) eyes within +/-1.0 D of the intended correction and 60 (79%)
      eyes within +/-0.5 D. At 12 months (n=46), the mean SE was -0.07 D (range: -1.375
      to +2.0 D) with 44 (96%) eyes within +/-1.0 D of the intended correction and 37
      (80%) eyes within +/-0.5 D. Myopic cylindrical corrections were attempted in 68
      eyes (range: -0.25 to -4.25 D) with vector analysis demonstrating a mean 85%
      correction. At last follow-up, UCVA was > or =20/20 in 47 (62%) eyes, > or =20/25
      in 63 (83%) eyes, and > or =20/40 in 75 (99%) eyes. Three (4%) eyes gained two
      lines of Snellen decimal equivalent best spectacle-corrected visual acuity
      compared to preoperative levels, 68 (89%) eyes showed no change or gained one
      line, and 5 (7%) eyes lost one line. None lost more than one line. Only 2 (3%)
      eyes at 6 to 12 months had more than +1 axial corneal haze and 50 (66%) showed no
      evidence of haze on slit-lamp examination. CONCLUSIONS: Laser subepithelial
      keratomileusis for myopia up to -11.00 D with the Schwind ESIRIS laser provides
      good refractive and visual outcomes, with acceptable visual recovery and minimal
      complications.

PMID- 16602315
TI  - A correction formula for the real intraocular pressure after LASIK for the
      correction of myopic astigmatism.
AB  - PURPOSE: To create a correction formula to determine the real intraocular
      pressure (IOP) after LASIK considering the altered corneal thickness, corneal
      curvature, and corneal stability. METHODS: This prospective clinical trial
      comprised 101 eyes of 59 patients (34 women and 25 men) that underwent LASIK with
      a mean preoperative spherical equivalent refraction of -6.3 +/- 2.17 diopters (D)
      (-3.0 to -11.5 D). Mean patient age was 32 +/- 9 years. Preoperatively and 6
      months postoperatively, IOP (by Goldmann applanation tonometry), keratometry (by
      topography), and central corneal thickness (CCT) (by ultrasound pachymetry) were
      evaluated. These parameters were measured in all patients between 8 and 11
      o'clock in the morning. RESULTS: Due to the LASIK procedure, IOP was reduced from
      16.5 +/- 2.1 mmHg (range: 12 to 22 mmHg) to 12.9 +/- 1.9 mmHg (range: 8 to 16
      mmHg). Multiple linear regression analysis of the IOP values before and after
      LASIK showed a significant correlation between the measured IOP and CCT and
      keratometry values (R2=0.631; P<.001). After LASIK, the biomechanical bending
      strength of the cornea is reduced by the cut so that the measured IOP must be
      additionally corrected by 0.75 mmHg. An equation containing all three changes is
      given: IOP (real) = IOP (measured) + (540-CCT)/71 + (43-K-value)/2.7 + 0.75 mmHg.
      CONCLUSIONS: Intraocular pressure measurements after LASIK for the correction of
      myopia are inaccurate as a consequence of changes in CCT, corneal curvature, and
      corneal flap stability. After LASIK, the measured IOP should be corrected to
      avoid false low IOP applanation readings.

PMID- 16602316
TI  - Accuracy of the WASCA aberrometer refraction compared to manifest refraction in
      myopia.
AB  - PURPOSE: To evaluate the accuracy of myopic refraction by a single measurement
      using the Wavefront Supported Custom Ablation (WASCA) aberrometer (Carl Zeiss
      Meditec AG, Jena, Germany). METHODS: We retrospectively compared the refractive
      errors obtained by manifest refraction and wavefront refraction (WASCA) in 50
      eyes of 25 consecutive myopic patients undergoing laser refractive surgery. The
      sphere ranged from -1.00 to -8.25 diopters (D) and cylinder from 0 to -3.75 D.
      WASCA measurements under cycloplegia were made and WASCA refractions calculated
      for a 6-mm analysis zone using the Seidel method within the WASCA. We used the
      manifest refraction as our best estimate of the true refractive error, therefore
      accuracy was defined as the difference between manifest refraction and that of
      the WASCA. Correlation coefficients and mean vector errors between manifest and
      WASCA refraction were calculated. RESULTS: High correlation was shown between
      manifest and WASCA refractions, with correlation coefficients (R2) of 0.97, 0.85,
      and 0.79 for M, J180, and J45, respectively. Mean power vector error (standard
      deviation) was 0.22 D (0.39), +0.03 D (0.21), and +0.03 D (0.13) for M, J180, and
      J45, respectively. Total dioptric power vector error was 0.43 D with 74% eyes
      within 0.50 D. CONCLUSIONS: When measuring normal myopic eyes, the concordance
      between manifest and WASCA refractions was found on average to be high; however,
      outlier measurements occurred.

PMID- 16602317
TI  - A new calibration set of phase plates for ocular aberrometers.
AB  - PURPOSE: To manufacture and test a set of phase plates for the calibration of
      ocular aberrometers and apply it to the calibration of an ocular laser ray
      tracing aberrometer. METHODS: The set of phase plates is made by a greyscale
      single-mask photosculpture in photoresist method. Each plate induces a given
      amount of a particular aberration (Zernike) mode. The set contains two subsets:
      1) pure Zernike modes to test the accuracy among different orders (from 3rd to
      7th, approximately 0.3 to 0.4 microm); and 2) plates having different amounts of
      the same mode, 3rd order coma ranging from 0.11 to 0.47 microm. After
      manufacturing, the plates were tested twice, as a crosscheck, measuring the
      aberration pattern of each plate with a Mach-Zehnder interferometer and a single
      pass Hartmann-Shack wavefront sensor. The set was then applied to the calibration
      of an ocular double-pass laser ray tracing aberrometer. RESULTS: Close agreement
      was found between the three types of measurement. The maximum difference between
      Hartmann-Shack and laser ray tracing measurements was 0.032 microm (ie,
      approximately lambda/20, half of the typical measuring error in human eyes). This
      permitted detection of a small bias in the ocular laser ray tracing aberrometer.
      CONCLUSIONS: The calibration set may be a powerful tool for the assessment of
      accuracy and reliability in ocular aberrometry. It discovered a small bias, which
      is almost impossible to detect when working with human eyes or trial lenses. This
      type of calibration tool is especially important in clinical environments.

PMID- 16602318
TI  - Refractive change induced by the LASIK flap in a biomechanical finite element
      model.
AB  - PURPOSE: To study the effect of varying four parameters on the refractive change
      induced by the LASIK flap. METHODS: Using a variety of patient-specific data such
      as topography, pachymetry, and axial length, a finite element model is built. The
      model is used in a non-linear finite element analysis to determine the response
      and change in optical power of the cornea as a function of a material property of
      the cornea (corneal elasticity), flap diameter and thickness, and intraocular
      pressure. RESULTS: The central flattening or hyperopic shift occurred atop the
      flap in all four of the simulated eyes tested with the creation of the LASIK
      flap. Of the four parameters tested, modulus of elasticity (Young's modulus) had
      the most profound effect on the results of hyperopic shift, varying from <0.5
      diopters (D) in the least elastic (stiffest) cornea to >2.0 D of hyperopic shift
      in the most elastic cornea. The depth of the lenticular cut was the second-most
      significant parameter tested varying from 0.24 D at 100 microns to 1.25 D at 275
      microns of depth. Varying intraocular pressure demonstrated less difference, and
      varying corneal flap diameter demonstrated the least difference in induced
      refractive change on the model. The hyperopic shift was noted to be greater in
      hyperopic than in myopic eyes (simulated) tested. CONCLUSIONS: Three-dimensional
      finite element analysis modeling of actual patient data could lead to a better
      understanding of the biomechanical response of corneal tissue to the lenticular
      flap creation and potentially for ablation patterns produced by the excimer
      laser. Understanding these biomechanical responses may lead to greater
      predictability and improvement of visual outcomes.

PMID- 16602319
TI  - Biomechanical model of corneal transplantation.
AB  - PURPOSE: Refractive consequences of corneal transplants are analyzed using
      corneal biomechanical models assuming homogeneous and inhomogeneous stiffness
      distributions across the cornea. Additionally, refractive effects of grafts
      combined with volume removal procedures are also evaluated to develop methods to
      reduce postoperative refractive management of patients. METHODS: Refinements of a
      two-dimensional finite element model are applied to simulate the biomechanical
      and refractive effects of different corneal transplant procedures: anterior
      lamellar keratoplasty, posterior lamellar keratoplasty, and penetrating
      keratoplasty. The models are based on a nonlinearly elastic, isotropic
      formulation. Predictions are compared with published clinical data. RESULTS: The
      model simulating the penetrating keratoplasty procedure predicts more change in
      the postoperative corneal curvature than models simulating anterior lamellar
      keratoplasty or posterior lamellar keratoplasty procedures. When a lenticle
      shaped tissue with a central thickness of 50 microns and a diameter of 4 mm is
      removed from the anterior corneal surface along with the anterior lamellar
      keratoplasty or posterior lamellar keratoplasty, the models predict a refractive
      correction of -8.6 and -8.9 diopters, respectively. CONCLUSIONS: Simulations
      indicate that a posterior lamellar keratoplasty procedure is preferable for
      obtaining a better corneal curvature profile, eliminating the need for specific
      secondary treatments.

PMID- 16602320
TI  - Visual acuity, contrast sensitivity, reading speed, and wavefront analysis:
      pseudophakic eye with multifocal IOL (ReSTOR) versus fellow phakic eye in non
      presbyopic patients.
AB  - PURPOSE: To compare the visual performance in the pseudophakic eye and the phakic
      eye in four patients who underwent unilateral intraocular lens (IOL)
      implantation. METHODS: Four patients presenting with unilateral cataract
      underwent ReSTOR (Alcon Laboratories, Ft Worth, Tex) IOL implantation in their
      nondominant eye, targeting emmetropia. RESULTS: Uncorrected near visual acuity
      was >20/32 in all operated eyes and best spectacle-corrected distance visual
      acuity was 20/16 for two eyes, 20/25 for one eye, and 20/32 for one eye. Reading
      speed was similar between the eyes, but not for critical print size. Contrast
      sensitivity was lower in the pseudophakic eyes. Wavefront analysis showed no
      considerable difference in total high order aberrations, coma, and spherical
      aberration between eyes for all patients. CONCLUSIONS: In young patients with
      unilateral cataract surgery, unilateral multifocal IOL implantation provides
      satisfactory visual acuity and may be considered an alternative treatment option
      in this patient population.

PMID- 16602321
TI  - Traumatic epithelial flap detachment after laser subepithelial keratomileusis.
AB  - PURPOSE: To report a case of corneal epithelial flap detachment 20 days after
      laser subepithelial keratomileusis (LASEK). METHODS: A 30-year-old man underwent
      LASEK for correction of myopia. On postoperative day 8, he was comfortable and
      the corneal epithelium healed completely with uncorrected visual acuity (UCVA) of
      20/20. On postoperative day 20, the corneal epithelial flap on the right eye
      detached and was lost during pressure patching after puncture of the hordeolum.
      RESULTS: The corneal defect was treated with a bandage contact lens,
      levofloxacin, and hyaluronic acid eye drops. Ten days after detachment, UCVA had
      improved to 20/20 and the epithelium had closed completely. CONCLUSIONS: Mild
      trauma can cause epithelial flap detachment during the early postoperative period
      of LASEK.

PMID- 16602322
TI  - Intracorneal asymmetrical rings for keratoconus: where should the thicker segment
      be implanted?
AB  - PURPOSE: To report a 20-year-old man who presented with monocular diplopia in the
      right eye with uncorrected visual acuity (UCVA) of 0.3 and best spectacle
      corrected visual acuity (BSCVA) of 1.0 with -0.50 -3.00 x 45 degrees. METHODS:
      Clinical examination and corneal topography revealed grade I keratoconus in the
      right eye. Intracorneal ring segments (INTACS; Addition Technology, Des Plaines,
      III) were implanted in May 2004 without surgical complications at 415 microm (70%
      of the corneal thickness), with the 450-microm segment implanted superiorly and
      the 250-microm segment inferiorly. RESULTS: For 2 months postoperatively, BSCVA
      remained at 0.4 with +1.50 -4.50 x 25 degrees. The segments were reversed,
      implanting the 450-microm (thick) segment inferiorly and the 250-microm (thin)
      segment superiorly. One week later, UCVA was 1.0 and remained stable for 3 months
      after reimplantation. CONCLUSIONS: This report shows that implanting the thicker
      segment inferiorly provides better visual results.

PMID- 16602323
TI  - Bacillus megaterium delayed onset lamellar keratitis after LASIK.
AB  - PURPOSE: To report the history and clinical presentation of a 23-year-old man who
      developed delayed onset lamellar keratitis in his right eye 2 weeks after
      uneventful LASIK for correction of myopia. METHODS: Initial clinical presentation
      suggested an infectious etiology, which led to therapeutic elevation of the LASIK
      flap and further microbiologic investigation with bacterial cultures. RESULTS:
      Bacterial cultures revealed Bacillus megaterium, which was sensitive to all
      antibiotics against which it was tested. Twenty-four hours after initiating
      aggressive topical and oral antibiotic therapy, symptomatic relief occurred in
      the affected eye. The patient's uncorrected final visual acuity at 1-year follow
      up was 20/15 in the right eye, and the stromal bed developed a faint peripheral
      non-visually significant scar. CONCLUSIONS: This case is an unusual presentation
      and course for microbial keratitis following LASIK, which occurred despite
      aseptic technique and fluoroquinolone antibiotic prophylaxis. Following
      refractive surgery one should be prepared to culture the lamellar interface in
      cases of suspected microbial keratitis and begin aggressive antibiotic therapy.

PMID- 16602324
TI  - Scanning electron microscopy of cochlea in new-born rats exposed to hyperbaric
      oxygen: preliminary report.
AB  - The aetiology of hearing loss in new-borns in neonatal intensive care is still
      debated. While the physiopathology of brain, lung and retina damage related to
      oxygen supplementation has been widely described, no studies have been carried
      out to define the relationship between hearing loss and supplementation of oxygen
      in new-borns. In the present investigation, the cochlear morphology of new-born
      rats was evaluated by means of scanning electron microscopy in order to assess
      morphological changes after supplemental oxygen administration. After treatment,
      electron microscopy revealed many changes in the morphology of outer hair cells,
      if compared to normal rats of the same age. The results suggest that cochlear
      changes are similar to those previously observed in other regions and may be
      related to a vascular mechanism of hypoxia-ischaemia and neovascularization
      and/or an oxidative stress.

PMID- 16602325
TI  - Sensitivity and specificity of mastoid vibration test in detection of effects of
      vestibular neuritis.
AB  - Aim of this study was to determine sensitivity and specificity of the mastoid
      vibration test in patients who had suffered an attack of vestibular neuritis.
      Results were compared with the caloric test and two bedside tests of vestibular
      function (head shaking test and head thrust test). Results are reported in 28
      patients who had a residual vestibular deficit 6 months after acute neuritis and
      in 25 healthy subjects. Mastoid vibration nystagmus was evoked in 21 patients but
      not in controls. In these patients, mastoid vibration test had a sensitivity of
      75% and specificity of 100%. Since one patient had inverted mastoid vibration
      nystagmus, specificity of identification on the pathological side was 95%.
      Sensitivity of the test increased with increasing severity of the vestibular
      lesion. Indeed, mastoid vibration nystagmus was induced in 93% of patients with
      caloric paralysis and in 58% of those with caloric paresis. Nystagmus could
      usually be modulated or elicited by stimulation of either mastoid. In the few
      patients in whom mastoid vibration nystagmus was elicited only from one side, or
      when there was a clear difference in intensity of the nystagmus induced on the
      two sides, the stimulated side was more often the affected side. Four patients
      still showed spontaneous nystagmus. The caloric test was abnormal in 26/28
      patients (93%) with paralysis in 16 and paresis in 12; 71% of patients had a head
      shaking induced nystagmus: 64% had an asymmetrical response in head thrust test.
      In conclusion, mastoid vibration test was overall more sensitive than head thrust
      test. Mastoid vibration test was slightly less sensitive than head shaking test
      in patients with severe residual deficit and more sensitive in patients with
      partial deficit. Mastoid vibration test, a valid, low cost clinical screening
      test for rapid detection of asymmetrical vestibular function, does not cause
      patient discomfort. It is suggested that this test be included in the diagnostic
      workup of all patients with suspected vestibular dysfunction.

PMID- 16602326
TI  - Diagnostic and treatment strategy of lateral semicircular canal canalolithiasis.
AB  - A new strategy for the diagnosis and treatment both of geotropic and apogeotropic
      Lateral Semicircular Canal Benign Paroxysmal Positional Vertigo is proposed. To
      this end, a new strategy of approach to Lateral Semicircular Canal Benign
      Paroxysmal Positional Vertigo is described in order to rapidly highlight both the
      side and the affected canal. Thus, in the first treatment session, using the so
      called "strategy of the minimum stimulus", a large percentage of cases are
      successfully treated, with the lowest number of vertigos for the patient.
      Following a review of the literature, 269 case studies, personally observed over
      a 4-year period, are described. The diagnostic strategy is performed by a single
      manoeuvre to determine whether the posterior semicircular canal or the lateral
      canal is affected. In the latter case, it is possible to highlight the affected
      sides both of the geotropic and apogeotropic forms. The therapeutic strategy
      comprises several liberatory manoeuvres, barbecue rotation techniques (Vannucchi
      Asprella, Lempert), and Gufoni manoeuvre by continuously monitoring the
      ampullofugal movement of the otoliths. Almost 98% of cases are successfully
      treated at the first treatment diagnostic-therapeutic session. This approach to
      Lateral Semicircular Canal Benign Paroxysmal Positional Vertigo allows a two-fold
      goal to be achieved, i.e., to effect both diagnosis and treatment at the first
      examination. Furthermore, thanks to the philosophy of the approach to Benign
      Paroxysmal Positional Vertigo, called the "Strategy of the minimum stimulus",
      patient compliance is very good since a very small number of vertigos are
      produced, and few neuro-vegetative disorders.

PMID- 16602327
TI  - A two-year course of specific immunotherapy or of continuous antihistamine
      treatment reverse eosinophilic inflammation in severe persistent allergic
      rhinitis.
AB  - Aim of the study was to evaluate the effect of a 2-year course of subcutaneous
      specific immunotherapy or continuous oral antihistamine treatment on the
      eosinophilic inflammation in nasal secretions of patients with severe persistent
      allergic rhinitis caused by house dust-mites. After informed consent, 31 rhinitis
      patients, sensitive to dust-mite antigens, were enrolled: 12 were randomly
      assigned to specific immunotherapy (group A), 11 to continuous oral antihistamine
      (cetirizine) treatment (group B), and 8 to an oral antihistamine (cetirizine) on
      demand (group C). Nasal scrapings were performed with a cotton-tipped swab and
      cells counted before and after 24 months of therapy. Intercellular adhesion
      molecule-1 and eosinophil cationic protein expression in cytological smears were
      assessed by immuno-histochemistry. All patients completed the study. The
      percentage of inflammatory cell types was comparable in the 3 groups at the
      beginning of the study. Eosinophils, identified as cells expressing eosinophil
      cationic protein, significantly decreased dropping to zero after 2 years of
      treatment in groups A and B, while no change was observed in group C. Expression
      of intercellular adhesion molecule-1 also decreased significantly in groups A and
      B, but not in group C. This decrease was associated with a significant reduction
      in epithelial shedding. In the 2-year period studied, specific subcutaneous
      immunotherapy and continuous oral antihistamine treatment were found to be
      effective in reducing eosinophilic infiltration and adhesion molecule expression
      in the nasal mucosa of patients with persistent allergic rhinitis. Furthermore,
      immunotherapy was more effective in controlling epithelial disruption while
      antihistamines appeared to be more active in controlling nasal inflammation. Both
      treatments induced a significant decrease in intercellular adhesion molecule-1
      expression in epithelial cells and also a dramatic reduction of eosinophil
      cationic protein positive staining. These parameters can be considered useful
      means for controlling the state of persistent inflammation which is typical of
      persistent respiratory allergy. Nasal scraping was demonstrated to be a simple
      and safe procedure for monitoring some nasal inflammation parameters.

PMID- 16602328
TI  - Dysmorphism of the middle ear: case report.
AB  - Although there are numerous publications in the literature describing the wide
      range of diagnosis, classifications and treatment of malformations of the hearing
      apparatus, even more variations can be found in clinical practice. Indeed, each
      individual case is unique as far as concerns pathogenesis, clinical course and
      treatment. The case reported herein describes a 12-year-old boy affected by
      cranio-facial dysmorphism and monolateral conductive hearing loss in the right
      ear: followed from radiological diagnosis--carried out to study a malformation of
      the ear pinna--to surgical treatment.

PMID- 16602329
TI  - Petrous apex arachnoid cyst: a case report and review of the literature.
AB  - Cholesterol granuloma and cholesteatoma are the two most common destructive
      lesions of the petrous apex. Arachnoid cyst is much less common. These three
      expansile lesions are often indistinguishable on clinical grounds. Accurate pre
      operative radiological diagnosis on computed tomography scan and magnetic
      resonance imaging is important in order to plan the appropriate treatment. Pre
      operative radiological differential diagnosis between primary cholesteatoma of
      petrous apex and a intrapetrous arachnoid cyst remains a significant problem. The
      following aspects need evaluation for recognition of intrapetrous arachnoid
      cysts: 1) an awareness of their existence, 2) homogeneous signal on T1 and T2
      weighted images, closely resembling cerebro-spinal fluid signal, 3) special
      heavily weighted T2 images on magnetic resonance imaging: fluid-attenuated
      inversion recovery imaging, 4) careful correlation of clinical-radiological data.
      Symptomatic arachnoid cysts are best treated with conservative drainage surgery
      through middle cranial fossa. A case of a petrous apex arachnoid cyst is reported
      which has been radiologically mistaken for a primary cholesteatoma and operated
      through an infratemporal fossa approach type B. The patient (40-year-old female)
      came to our attention with right trigeminal pain which had been present for one
      year and dizziness. Neurotologist and skull-base surgeons should include
      arachnoid cyst as a rare possibility in the evaluation and treatment of petrous
      apex cystic lesions.

PMID- 16602330
TI  - Long-surviving case of adenosquamous carcinoma of the larynx: case report and
      review of literature.
AB  - A singularly long-surviving (15 years) disease-free case of a stage II
      adenosquamous carcinoma of the larynx is described. A review of the literature
      reveals that prognosis of this aggressive malignant neoplasm is poor (mean 2-3
      years free of disease) on account of local recurrences, early cervical lymph node
      metastasis and distant dissemination. This long survival rate emphasises the
      importance of early radical surgical treatment and the choice of total
      laryngectomy with neck dissection in stage II laryngeal neoplasm.

PMID- 16602331
TI  - Informed consent in ENT. Patient's judgement about a specific consensus form.
AB  - The concept of informed consent was first used in the 60's. The meaning of this
      term is the need of a preliminary and valid consensus that places the doctor in
      an authorised condition whereby he is able to carry out his work. Notwithstanding
      the importance and delicacy of this topic and the potentially serious
      consequences, there is not, as yet, universal behaviour, on the part of doctors,
      regarding the mode of information and documentation on how the patient be
      informed. In a previous article, the authors outlined the best approach, on the
      part of the doctor in regard to the patient, in order to obtain valid informed
      consent. In particular, the specific information for each disease was proposed
      and this was not limited only to aspects related to type of treatment and
      possible risks, but thorough, with regard to adhering to the logical course (case
      history, objective tests, instrumental diagnosis carried out, etc.) that led the
      doctor to a certain diagnosis and a description of the proposed treatment
      possibilities as well as the treatment modalities excluded, with relative
      reasons. The study was designed in such a way as to define the degree of
      acceptance that this informative method has on the patients. This was achieved by
      means of a questionnaire filled in by 254 patients hospitalised in our
      department, about to undergo surgery. Judgement was substantially positive, in
      that, > 70% of patients agreed that the information was quite or very good, and
      90% considered it sufficient or better. This demonstrates that even those
      subjects who received little information, were, in fact, satisfied with that
      given. The patient/doctor relationship was also judged positive. The patients
      felt that it was important to be kept informed about their condition, regardless
      of the form (written or spoken). In conclusion, the outcome of the questionnaire
      demonstrates the appreciation. on the part of the patients, regarding the
      procedure of information used in seeking consensus.

PMID- 16602333
TI  - Famous figures: Franz Kafka (1883-1924).

PMID- 16602332
TI  - [The origin of informed consent].
AB  - The principle of informed consent, aimed at the lawfulness of health assistance,
      tends to reflect the concept of autonomy and of decisional autodetermination of
      the person requiring and requesting medical and/or surgical interventions. This
      legal formula, over the last few years, has gained not only considerable space
      but also importance in the doctrinal elaboration and approaches, as well as
      juridical interpretations, thereby influencing the everyday activities of the
      medical profession. Informed consent is still the object of continuous
      explorations, not only asfar as concerns the already confirmed theoretical
      profile but, instead, the ambiguous practical and consequential aspect. Analysing
      how the concept and role of consensus was born and developed with the more
      adequate and reasonable excursions to make it valid and obtain it, it is
      impossible not to take into consideration, on the one hand, the very ancient
      philosophical origins and, on the other, the fact that it was conditioned by
      religion with the moral aspects and the accelerated deontological evolution with
      pathways parallel to the needs and the progress offered by new forms of treatment
      and novel biotechnological applications. The principle of consent is a relatively
      new condition. In fact, already in the times of not only the Egyptian
      civilisation, but also the Greek and Roman, documents have been found which show
      how the doctor's intervention had, in some way, first to be approved by the
      patient. Plato (law IV) had already foreseen the problems, the procedures and the
      modes of information which are, in synthesis, at the root of the principles of
      the present formula of informed consent and correlated the practice of the
      information and consensus with the quality and social position of the patient.
      The only guarantee that the patient might have, derived from a fundamental
      principle of medicine of all times: "in disease, focus on two aims, to improve
      and not to cause damage". A figure can be recognised, in the Hippocratic
      physician, that cared about the patient's suffering, but never neglected looking
      after his own outcome, endeavouring to avoid becoming involved in lack of success
      and death of a patient. The concept of consensus is inexistent, albeit, there is
      an awareness of the presence of precautious and preventive information. In the
      behaviour of doctors, in ancient times, it is not difficult to recognize the true
      motives and the real reasons that, already in those days, give rise to the
      necessary "defensive medicine" particularly as far as concerns the social status
      of the patient. Already from the early origins, continuing the Hippocratic
      tradition, the relationship between doctor and patient was consolidated, based
      upon two very definite criteria, represented, on the one hand, by the
      professional duty of the physician to do what is bestfor the patient and, on the
      other, the duty of the patient to completely accept the physician's decisions and
      intervention. The Hippocratic physician respected a principle of professional
      responsibility which was more religious and of a moral type, but, from a legal
      point of view, very weak inasmuch as it depended upon regulations elaborated by
      human beings. The conviction and certainty that the physician acted, in the
      interest of his patient's well-being, has been passed down over the centuries
      endowing the physician with moral authority and a kind of legal impunity,
      conditions which corresponded, in an almost reflection-likefashion, with the duty
      of obedience and subjection, on the part of the patient. Christianity was grafted
      into this consolidated vision of the sacral character of medicine and medical
      practice, which did not substantially change the Hippocratic type of ethical
      behaviour. Non only the population but also the Christian physician was aware of
      the religious importance of his intense activity as a mission and compared to a
      special kind of priesthood in safe-guarding health, considered as a gift of God.
      Therefore, invested with this authority which derived from his professional role
      and from his very work, he felt it his duty to guide the patient, deciding and
      for him. The patient is an ignorant person who does not have the knowledge, the
      intellectual capacity or moral authority to oppose or disagree with the wishes
      and decisions of the physician who, instead, on account of his doctrine, knows
      exactly what is goodfor him. In this regard, if we were to speak of consensus
      concerning the physician's intervention, he would be considered useless in as
      much as obvious and understood when seeking help. The attitude of the patient
      towards the physician has always tended to one of strong faith and characterized
      by psychological subjection borne out by traditions thousands of years old. A
      patient who was sick, again, as an attitude of respect and gratitude, followed
      the treatment but never asked for any explanations regarding the therapeutic
      effects and the physician refrained from taking any initiative to inform the
      patient or his/her family. Each phenomenon, therefore, has a precise origin, a
      well-defined history and when its importance tends to significantly condition the
      activities concerning Man, a desire emerges to learn the origin and the history.
      As is well known, a trial commenced in Nuremberg, on December 19, 1946, of Nazi
      doctors and a code was defined in which the judges, all Americans, clearly
      emphasized a view of medical research and technology: science should never
      transform or consider human beings as an instrument to be employed for scientific
      purposes. In actual fact, documents exist providing evidence that a few decades
      before the drawing up of the Nuremberg Code, the need had been expressed, in
      Germany itself to somehow make medical interventions and actions legal by means
      of the use and practice of consensus. The moral and ethical principles in those
      documents, even if not available as bibliographic references in the English
      literature, certainly merit, from a historical viewpoint to be considered as
      conceptual elements and doctrinal and socio-cultural products, even if at that
      time, of little practical importance, which belong to the European culture and,
      in particular, and almost paradoxically, in the light of what happened, to the
      German culture. The United States of America is held to be the country of origin
      of informed consent, the initial aim of which was make sure that the correct
      dignity of the patient's independence be reserved at the time of decision making
      and choice of medical options. Reports on this topic, in fact, first appeared in
      the USA, at the beginning of the 18th Century, with problems focusing on and
      limited to only the simple rights of the patient in giving his/her approval of
      the health intervention later to be conceptually developed, along the lines of an
      itinerary with, at intervals, famous legal actions, until in the 20th Century,
      informed consent was reached, a criterion that, as is well known, foresees and
      includes not only the important and fundamental autonomy of the patient to
      decide, which stems ones personal rights, but also the essential objective
      element, which is, information. The expression informed consent has simply been
      transposed in Italian and roughly translated in an ambiguous fashion into
      "consenso informato" when, on the contrary, it should be referred to as
      "informazione per il consenso" "information for consensus" not only to respect
      the concept but, surely, for a more correct deciphering and a more precise
      interpretation related to the numerous concepts it presupposes and implies.
      Information and consent may be compared to the two sides of the same coin. These
      are the two important pillars that coincide and are joined giving weight to the
      medical responsibility, as far as concerns consent to the health intervention: on
      the one hand, having obtained consent,following correct and sincere information
      interpreted and deciphered as an important phase and an essential indicator of
      correct, scrupulous medico-professional procedure and, on the other, the
      consensus itself conceived as a duty aiming at the maximum respect of the rights
      to autodetermination, independence and autonomy of the patient, as a person. At
      the beginning of the Nineties, as we have seen, we were made aware of a series of
      legal actions regarding medical responsibility which was greatly conditioned by
      the Anglosaxon influence which initially induced many Italian magistrates and
      forensic physicians to adopt an extremely rigid attitude with no attempt to
      comply, in any way, with the culture and traditions of our country and our
      tradition which has always been inspired by good common sense, both medical and
      human. The American experience has been very rapidly adopted, by some, without a
      profound, complete and necessary historical and evolutional analysis aimed at
      those intertwined principles that have been motifs that have gradually led to the
      legal references in those emblematic cases referred to, the conclusions of which
      continue to attract a great deal of attention. In Italy, the legal and doctrinal
      evolution of informed consent, even if following a little more rapidly the
      traces, steps, problems and interpretations of the various aspects drawn up,
      characterized and applied in the United States, has not only occurred at a later
      time, but, despite reaching the same meaningful objectives, the same
      considerations, the same importance, and, unfortunately, the same inconveniences,
      has had quite different aims, approaches and articulations. In this respect, it
      is enough to focus attention on the different cultural traditions and religious
      routes, on the different doctrinal background, the particular historical origins
      and the individual legal aspects, all extremely different one from the other.
      (ABSTRACT TRUNCATED)

PMID- 16602334
TI  - Trauma week 2005--an injury prevention and health promotion initative for the
      community.

PMID- 16602335
TI  - The evolution of trauma nursing and the Society of Trauma Nurses: a noble
      history.

PMID- 16602336
TI  - Case report: stroke versus carotid artery injury.
AB  - A potentially serious consequence associated with blunt force trauma to the neck
      is an injury to the carotid artery. Initially the blunt carotid injury may be
      missed or it may be delayed in presentation; therefore one must have a heightened
      index of suspicion when considering the patient's mechanism of injury. The
      purpose of this article is to present a case report of blunt carotid injury and
      implications for healthcare workers.

PMID- 16602337
TI  - Nurse driven protocol for head injured patients on warfarin.
AB  - The trauma quality improvement committee at our facility identified a significant
      number of patients on warfarin presenting to the emergency center after minor
      head trauma that subsequently expired from their intracranial hemorrhage prior to
      appropriate intervention. An analysis of this patient population identified
      multiple areas of delay. A collaborative effort between the emergency center
      nurses and the trauma service personnel resulted in a formal protocol to address
      each component of delay and expedite the process. Since implementation of this
      nursing driven protocol we have dramatically decreased the time to (1) Emergency
      Center Physician evaluation, (2) completion of head computerized tomography, (3)
      reversal of anticoagulation with fresh frozen plasma (FFP), and (4) most
      importantly, patient mortality rate. We conclude that this nursing driven
      protocol is effective in decreasing the mortality rate by eliminating diagnostic
      and therapeutic delays in this high-risk patient population.

PMID- 16602339
TI  - White uniforms.

PMID- 16602338
TI  - Transient spinal cord injuries in the young athlete.
AB  - Spinal cord injuries are be potentially devastating. Despite initial
      presentation, they may be permanent or transient. A small percentage of spinal
      cord patients with motor or sensory dysfunction recover rapidly and completely
      with no neurological sequelae. Cervical cord neurapraxia is a frequent cause of
      transient neurologic symptoms. This transient neurological phenomenon involves
      bilateral motor paralysis and/or sensory manifestations that appear in the
      absence of any structural deficiencies of the cervical spine as evidence by
      negative diagnostic imaging. All patients with any history of neurologic deficits
      should be assessed thoroughly and rendered care appropriately to avoid secondary
      injury. This article will present a case study of a 15-year-old high school
      football player who complained of motor and sensory deficits after tackling
      another player. Treatment was provided and his neurological symptoms resolved
      completely. The pathophysiology of cellular injury related to the spinal cord and
      cervical cord neurapraxia is reviewed. In addition treatment modalities such as
      high dose steroids to reduce secondary spinal cord injury are discussed.

PMID- 16602340
TI  - White uniforms.

PMID- 16602341
TI  - Confidentiality and the continuing competence program.

PMID- 16602342
TI  - A systematic approach to maximizing nursing scopes of practice.

PMID- 16602343
TI  - A fear of trying: dysfunctional conservatism.
AB  - As the American Psychoanalytic Association faces mounting external pressures that
      threaten its very survival, its leadership and members appear increasingly
      preoccupied with issues of internal governance and training standards. This
      inward gazing, though in keeping with analysts' personality and occupational
      traits, serves to obscure and defend against the anxieties associated with
      threats from the surround. Such maladaptive defensive activity contributes to
      organizational stagnation, dysfunctional conservatism, and a "fear of trying."
      Suggestions to combat this self-defeating behavior are offered.

PMID- 16602344
TI  - Identification: psychoanalytic and biological perspectives.
AB  - In recent attempts to bring psychoanalysis into greater contact with other
      sciences, a number of works have explicated neural science concepts and phenomena
      -affect, memory, consciousness--for the psychoanalyst. These efforts have helped
      analysts build a more scientific foundation for their theory and practice. A
      related task remains--namely, to take psychoanalytic concepts and see how they
      relate to other sciences. The concept of identification has a long history in
      psychoanalytic theory. It is seen in parent-child interactions, in teaching and
      mentoring relationships, and in psychoanalysis and psychotherapy. Neuropsychology
      and evolutionary biology have explored the phylogenetic precursors of
      identification, while genetics and infant observation provide insights into
      individual processes of identification. Finally, neuroscience, particularly
      recent studies of mirror neurons, offers information about the biological
      mechanisms of imitation and the relationship of imitation to identification.
      Findings from these sciences are presented in an effort to further the
      psychoanalytic understanding of identification, especially its biological
      underpinnings.

PMID- 16602345
TI  - Mirror neurons and intentional attunement: commentary on Olds.

PMID- 16602346
TI  - Research-informed reflections on the processes of introjection and
      identification: commentary on Olds.

PMID- 16602347
TI  - Countertransference in defense enactments.
AB  - A clinical term is introduced to capture a defense that develops with the
      patient's deepening but fleeting awareness of painful transference feelings. The
      analyst's attention to countertransference in such situations is central to the
      analysis of these defenses. An attempt is made to distinguish defense enactments
      from other types of defenses, and to differentiate the analyst's
      countertransference reaction to this type of defense from countertransference
      reactions that might appear similar. The reasons for this dynamic in the
      interpersonal space are explored, and a clinical example that describes this
      phenomenon in the analytic moment is given.

PMID- 16602348
TI  - Action as ejection.
AB  - The systematic analysis of acting-out episodes can be used in assessing analytic
      progress. Variables to be considered are the nature of the wish, the type of
      defense, and the degree of concreteness (versus symbolization) of the mental
      processes used in attempting actualization (as distinct from the resort to
      action). Two acting-out episodes of a borderline patient who acted out as a
      character trait, both occurring outside the analytic setting, are presented as
      illustrations. In the first one, occurring relatively early in the analysis, when
      split-off negative and positive self-images had to be rigidly maintained,
      ejection of the negative self-image was actualized via the regressive use of a
      symbolic equation and the mechanism of displacement, obliterating the distinction
      between an internal feeling and an external thing that here was literally thrown
      out. The later episode, occurring after the split was healed and within the
      context of a frustrating heterosexual involvement, contained an acted-out
      allusion to identification and competition with the mother. As in a dream, via
      associations, an unconscious wish for oedipal victory was revealed. Whereas in
      the first episode the goal of ejection was central, with splitting and denial the
      underlying defenses, it was absent from the second, in which an attempt was made
      to actualize a repressed infantile wish and made greater use of symbolization. It
      is concluded that acting-out episodes at different periods of the analysis, when
      systematically analyzed, can serve in assessing a patient's progress.

PMID- 16602349
TI  - Autistic defenses in agoraphobic syndrome: "flat" objects and the retardation of
      projective identification.
AB  - The function of autistic defenses in the generation of agoraphobic symptoms is
      explored in the case of a patient treated in psychoanalytic psychotherapy. The
      therapist's growing awareness of autistic modes of relating in the case
      facilitated various changes in the transference relationship. Although oedipal
      concerns are seen as important, a formulation is presented whereby autistic modes
      of generating experience are viewed as fundamental to an understanding of
      agoraphobic experience. Clinical findings in the transference-countertransference
      relationship led to the additional observation that the retardation of defensive
      forms of projective identification further contributed to the patient's
      agoraphobic difficulties. This formulation is tied theoretically to the idea that
      agoraphobic experience occurs when the dialectic between paranoid-schizoid and
      autistic-contiguous modes of generating experience collapses. The treatment
      implications of these observations are briefly explored.

PMID- 16602350
TI  - Paul Gray's narrowing scope: a "developmental lag" in his theory and technique.
AB  - A cental thesis of Paul Gray's work is that a "developmental lag" pervades modern
      psychoanalysis in its failure to assimilate and apply knowledge gained about the
      role of the unconscious ego in intrapsychic life. But Gray himself, it is
      proposed, has become a victim of a new "developmental lag," of his own
      construction. As he somewhat single-mindedly pursued the ramifications of his
      "developmental lag" concept, Gray may have foreclosed on some noteworthy ideas
      developing around him. The most important example is his claim--herein refuted-
      that proper interpretive technique can avoid being infused with transference. He
      also seems to have rejected the theoretical importance of the internalization of
      the analyst and the clinical usefulness of countertransference. While emphasizing
      defense analysis, he ignores defenses such as splitting, denial, and disavowal as
      substantive problems for his technique of close-process attention. Gray's
      "undoing" of the rapprochement between "ego analysis" and "id analysis" by
      viewing the matter as an either-or proposition undermines the very real value of
      his contribution to the field.

PMID- 16602351
TI  - "I no longer believe": did Freud abandon the seduction theory?
AB  - Recent accounts of the seduction theory and the question of its abandonment have
      emphasized the continuity of Freud's work before and after the seduction theory,
      claiming that Freud did not abandon his concern with the event of seduction but
      rather came to appreciate that an understanding of fantasy was also essential.
      This claim is challenged. It is shown that Freud did abandon the passionate
      concerns of his seduction theory for the most part; that he left behind his early
      interest in reconstructing unconscious infantile incest and focused instead on
      later, conscious seduction; that he at times clearly reduced apparent paternal
      incest to fantasy; that he turned away from the phenomenology of incest he had
      begun to develop; and that he theoretically nullified the value of the difference
      between real and fantasied seduction. It is also shown that, contrary to a
      persistent concern in psychoanalytic history, attention to actual seduction need
      not detract from the essential psychoanalytic concern with fantasy and infantile
      sexuality. Thinking about incest specifically illuminates the capacity for
      fantasizing, the core of the Freudian psyche. In this way the intuition of the
      seduction theory that there is something of distinctive psychoanalytic
      significance about incest finds support.

PMID- 16602352
TI  - The aim of the training analysis.
AB  - Although the training analysis is considered by many to be the most important
      element of a candidate's analytic training, its aim remains unclear. Some think
      of the training analysis as being a strictly therapeutic tool, while others
      assign it a more frankly educational role. This paper reviews the literature on
      this topic from Freud to the present, discusses the problems that lack of clarity
      about the aim of the training analysis generates for psychoanalytic education,
      and proposes future research in this area.

PMID- 16602353
TI  - How do we evaluate learning from the curriculum? Thirty phone interviews with
      Institutes of the American Psychoanalytic Association.
AB  - A telephone survey of curriculum directors of the thirty institutes of the
      American Psychoanalytic Association revealed that 75 percent of institutes highly
      value the importance of evaluating what candidates learn from the curriculum.
      Paradoxically, however, most institutes do not do evaluations in this area.
      Typically, institutes evaluate candidates' satisfaction with courses, or their
      attendance and conduct in classes, rather than learning per se. Some institutes
      have more rigorous evaluation methods, including oral exams. Objections to
      evaluating what candidates learn included (1) evaluations involve too much work;
      (2) evaluations of learning are considered inappropriate or invalid; (3)
      evaluations would hurt candidates, faculty, the learning process, and the
      institute. Some curriculum directors dismissed these objections, contending that
      it is the responsibility of psychoanalytic educators to set teaching goals and
      evaluate learning.

PMID- 16602354
TI  - Mentalization, affect regulation, and development of the self. Panel report.

PMID- 16602355
TI  - More transitions...and parachutes.

PMID- 16602356
TI  - Parachute use to prevent death and major trauma related to gravitational
      challenge: systematic review of randomised controlled trials.
AB  - OBJECTIVES: To determine whether parachutes are effective in preventing major
      trauma related to gravitational challenge. Design Systematic review of randomised
      controlled trials. DATA SOURCES: Medline, Web of Science, Embase, and the
      Cochrane Library databases; appropriate internet sites and citation lists. STUDY
      SELECTION: Studies showing the effects of using a parachute during free fall.
      MAIN OUTCOME MEASURE: Death or major trauma, defined as an injury severity score
      > 15. RESULTS: We were unable to identify any randomised controlled trials of
      parachute intervention. CONCLUSIONS: As with many interventions intended to
      prevent ill health, the effectiveness of parachutes has not been subjected to
      rigorous evaluation by using randomised controlled trials. Advocates of evidence
      based medicine have criticised the adoption of interventions evaluated by using
      only observational data. We think that everyone might benefit if the most radical
      protagonists of evidence based medicine organised and participated in a double
      blind, randomised, placebo controlled, crossover trial of the parachute.

PMID- 16602357
TI  - The true goal of evidence-based dentistry.

PMID- 16602358
TI  - Evidence-based dentistry 2006: where are we?

PMID- 16602359
TI  - Evidence and clinical improvement: current experiences with dental implants in
      individuals with rare disorders.

PMID- 16602360
TI  - An example of hierarchy of evidence vs hierarchy of information.

PMID- 16602361
TI  - An 18-year retrospective survival study of full crowns with or without posts.
AB  - PURPOSE: This study of full crowns investigated long-term survival in
      relationship to biologic and technical variables. MATERIALS AND METHODS: A total
      of 1,037 full crowns in 456 patients, made in an undergraduate university clinic,
      were evaluated over an 18-year period. All patients were offered a supportive
      maintenance program. Failures of full crowns were classified as irreversible
      (loss of full crown and/or tooth) or reversible (full crown intact after
      conservative treatment) complications and as biologic or technical/patient
      related failures. RESULTS: The Kaplan-Meier survival rate after 18 years was 78%.
      No statistically significant differences were found between restorations in the
      maxilla and mandible (P= .150); between restorations on molars, premolars, and
      anterior teeth (P = .671); and between restorations on posts and cores compared
      to restorations without posts and cores (P = .602). For the surviving
      restorations, the improved plaque score over time was statistically significant
      (P = .001). Biologic failures (66.4%) resulting in removal were more common than
      technical and patient-related failures (33.6%). Caries was the most frequent
      reason for failure (irreversible complication). CONCLUSION: The survival of full
      crowns made in an undergraduate university clinic during an 18-year period is
      comparable to the results published by university departments or private
      practitioners. Plaque scores and bleeding on probing were not directly related to
      failures. Occurrence of a previously reversible complication is a predicting
      factor for an irreversible complication. A reversible complication within the
      first 2 years will probably lead to an early irreversible complication.

PMID- 16602362
TI  - A 20-year retrospective survival study of fixed partial dentures.
AB  - PURPOSE: This study of fixed partial dentures (FPDs) evaluated the long-term
      efficacy and determined frequencies and causes of failures. MATERIALS AND
      METHODS: A total of 322 FPDs in 193 patients, fabricated at an undergraduate
      university clinic, were evaluated over a 20-year period. All patients were
      invited to participate in a supportive maintenance program. Failures of the FPDs
      were divided into irreversible complications (loss of FPD/abutment) and
      reversible complications (FPD intact after conservative treatment) and into
      biologic and technical/patient-related failures. RESULTS: The Kaplan-Meier
      survival rate after 20 years was 66.2%. Statistically significant differences in
      survival rates were found between FPDs without post-and-core abutment teeth as
      compared to FPDs with at least one post-and-core abutment tooth (P = .002) and
      for vital abutments versus post-and-core abutments (P = .001), but significant
      differences were not found between restorations in the maxilla and mandible (P =
      .27). Caries and loss of retention were the main reasons for failure and
      accounted for 61% of the failures. CONCLUSION: The survival of FPDs by
      undergraduate students at a university clinic during a 20-year period was
      comparable to the results published by university departments or general
      practitioners. Occurrence of a previously reversible complication is a predictive
      factor for an irreversible complication later on. A reversible complication
      within the first 2 years will probably lead to an early irreversible
      complication.

PMID- 16602363
TI  - Sleep and depression as risk indicators for temporomandibular disorders in a
      cross-cultural perspective: a case-control study.
AB  - PURPOSE: We conducted this case-control study to determine the role of 2
      neuropsychologic variables (sleep and depression) as possible risk indicators for
      the development of temporomandibular disorders (TMD). MATERIALS AND METHODS:
      Neuropsychologic tests, traditional signs and symptoms of TMD, and social and
      economic variables were analyzed. Seventy-two predominantly muscle-related TMD
      patients (Research Diagnostic Criteria for TMD groups Ia, Ib, and IIIa) and 30
      age- and sex-matched pain-free controls were included in the population. RESULTS:
      Overall, TMD patients had statistically significantly higher sleep and depression
      scores on the Sleep Assessment Questionnaire and on the Brazilian Portuguese
      version of the Beck Depression Inventory, with odds ratios of 5 and 1.6,
      respectively. These results remained unchanged even after controlling for 8
      confounders in the logistic regression analysis. Spontaneous pain and pain on
      palpation (grade 2 or higher) were also statistically significantly worse in TMD
      patients. In the forward-step logistic regression analysis, we also found that
      the combination of our best TMD predictors (ie, sleep, cigarettes, alcohol) had a
      better predictive value (percent agreement = 78.69%) than when the variables were
      analyzed alone. CONCLUSION: Sleep and depression are considered important risk
      indicators for the development of TMD.

PMID- 16602364
TI  - Six-year clinical performance of all-ceramic crowns with alumina cores.
AB  - PURPOSE: The aim of the study was to evaluate the clinical performance of Procera
      Alumina AllCeram crowns (Nobel Biocare). MATERIALS AND METHODS: In 70 patients,
      61 anterior and 46 posterior teeth were provided with single crowns and cemented
      with a glass-ionomer cement. RESULTS: Four patients were lost to follow-up. Six
      crowns had to be removed, all because of nonreparable fracture. At 6 years, the
      cumulative survival rate was 94.3% for all crowns, 96.7% for anterior crowns, and
      91.3% for posterior crowns (survival = not removed). Most of the defects occurred
      within the first 1.5 years. CONCLUSION: The findings indicate a good clinical
      prognosis of both anterior and posterior Procera Alumina crowns.

PMID- 16602365
TI  - Implant-supported mandibular overdentures retained with ball or telescopic crown
      attachments: a 3-year prospective study.
AB  - PURPOSE: The aim of the present study was to evaluate implant survival, peri
      implant conditions, and prosthodontic maintenance requirements for implant
      supported mandibular overdentures in atrophic mandibles retained with ball or
      resilient telescopic crown attachments during a 3-year period. MATERIALS AND
      METHODS: Twenty-five patients with edentulous mandibles each received 2 Camlog
      root-form dental implants in the mandibular interforaminal (canine) region. The
      denture attachment system was chosen randomly; 13 patients received ball
      attachments and 12 patients received resilient telescopic crowns. Implant
      survival, implant mobility (Periotest values), and peri-implant conditions such
      as bone resorption, pocket depth, Plaque Index, Gingiva Index, Bleeding Index,
      and Calculus Index values were assessed for each implant. In addition, detailed
      prosthodontic maintenance was evaluated during the follow-up period and the 2
      retention modalities were compared. RESULTS: There were no differences in implant
      survival, implant mobility (Periotest values), and peri-implant conditions
      between the 2 retention modalities. During the 3-year period significantly more
      complications/interventions for maintenance purposes were registered in the ball
      group (62 interventions) than in the telescopic crown group (26 interventions; P
      < .01). CONCLUSION: The results indicate that both ball attachments and resilient
      telescopic crowns used on isolated implants in the edentulous mandible are viable
      treatment options. Implant success and peri-implant conditions did not differ
      between ball attachments and telescopic crowns used as retention modalities for
      implant overdentures, but the frequency of technical complications was
      significantly higher with ball attachments than with resilient telescopic crowns.

PMID- 16602366
TI  - Attitudes toward the shortened dental arch concept among Swedish general dental
      practitioners.
AB  - PURPOSE: The purpose of this investigation was to obtain the opinions and assess
      the attitudes of Swedish general dental practitioners in private practice versus
      a public health care setting regarding management of patients with a shortened
      dental arch (SDA). MATERIALS AND METHODS: A questionnaire containing different
      statements regarding the SDA concept was sent to a random sample of 189
      clinicians. Differences between male and female practitioners and between private
      practitioners (PPs) and those employed by the Public Dental Health Service (PDHS)
      were tested for statistical significance by the Student t test. RESULTS: The
      response rate was 54% (102 clinicians). Among the respondents, 62% were men and
      38% were women. Fifty-six percent were PPs and 44% were employed by the PDHS. The
      results showed small differences in attitudes between various groups of
      practitioners but large individual variations. In general, Swedish general
      practitioners had a positive attitude toward the SDA concept with respect to oral
      function and oral comfort. They recognized few risks with a dentition lacking
      molar support, although female clinicians were more risk conscious. PPs expressed
      fewer advantages in using the SDA concept than PDHS practitioners with respect to
      the reduced risk for overtreatment, better patient economy, and the ability for
      older patients to keep their teeth. CONCLUSION: The results from this
      questionnaire study indicate that, overall, Swedish general practitioners have an
      affirmative opinion toward the SDA concept.

PMID- 16602367
TI  - Medial mandibular flexure and maximum occlusal force in dentate adults.
AB  - PURPOSE: Medial mandibular flexure (MMF) is the functional narrowing of the
      mandible during opening and protrusion movements, which may affect conventional
      or implant-supported prostheses. This study evaluated the association among MMF,
      maximum occlusal force (MOF), gender, weight, height, body mass index (BMI), and
      age in 80 dentate adult subjects (40 women, 40 men; age range 20 to 38 years).
      MATERIALS AND METHODS: Bilateral MOF was measured using a cross-arch force
      transducer placed in the first molar region. For MMF calculation, impressions of
      the mandibular occlusal surface were made with vinyl polysiloxane putty material
      in rest (R), maximum opening (O), and maximum protrusion (P). The impressions
      were scanned, and the images were processed using Adobe Photoshop software.
      Reference points were selected on the occlusal surface of the contralateral first
      molars, and the linear intermolar distance was measured using Image Tool
      software. MMF was calculated by subtracting the intermolar distance during
      opening or protrusion from the intermolar distance during rest. RESULTS: Mean
      values of MOF were 698.14 N for women and 1,009.48 N for men; MMF-O was 0.146 mm
      and MMF-Pwas 0.15 mm for the total sample. No correlation was found between MOF
      and MMF (r = 0.02 for MMF-O; r = 0.11 for MMF-P; P > .05) or between MMF and
      weight, height, BMI, or age. MOF was significantly associated (P <.001) with
      weight (r = 0.509), height (r = 0.459), and BMI (r = 0.423), but not with age (r
      = 0.009). CONCLUSION: These results suggest that MMF is not associated with MOF
      in this sample of dentate adults.

PMID- 16602368
TI  - Comparison of the retention of 5 core materials supported by a dental post.
AB  - PURPOSE: This study evaluated the retention of dental post heads (No. 2 Flexi
      Post) embedded in 5 core materials (1 automix resin composite, 2 hand-mixed resin
      composites, and 2 glass ionomers). MATERIALS AND METHODS: Samples were prepared
      by embedding post heads in 4.5-mm-thick disks of core material. RESULTS: The
      resin composite materials provided significantly more retention than the glass
      ionomer-based materials. The post head retention of the automix resin composite
      was comparable to that of the hand-mixed resin composites. CONCLUSION: Unlike the
      resin composite samples, all the glass-ionomer samples fractured during testing.
      This is an unacceptable condition for a clinically successful restoration.

PMID- 16602369
TI  - Failure analysis of ceramic clinical cases using qualitative fractography.
AB  - PURPOSE: To educate dental academic staff and clinicians on the application of
      descriptive (qualitative) fractography for analyses of clinical and laboratory
      failures of brittle materials such as glass and ceramic. MATERIALS AND METHODS:
      The fracture surface topography of failed glass, glass fiber-reinforced
      composite, and ceramic restorations (Procera, Cerestore, In-Ceram, porcelain
      fused-to-metal) was examined utilizing a scanning electron microscope. Replicas
      and original failed parts were scrutinized for classic fractographic features
      such as hackle, wake hackle, twist hackle, arrest lines, and mirrors. RESULTS:
      Failed surfaces of the veneering porcelain of ceramic and porcelain-fused-to
      metal crowns exhibited hackle, wake hackle, twist hackle, arrest lines, and
      compression curl, which were produced by the interaction of the advancing crack
      with the microstructure of the material. Fracture surfaces of glass and glass
      fiber-reinforced composite showed additional features, such as velocity hackle
      and mirrors. The observed features were good indicators of the local direction of
      crack propagation and were used to trace the crack back to an initial starting
      area (the origin). CONCLUSION: Examples of failure analysis in this study are
      intended to guide the researcher in using qualitative (descriptive) fractography
      as a tool for understanding the failure process in brittle restorative materials
      and also for assessing possible design inadequacies.

PMID- 16602370
TI  - Comparison of mechanical strength of palatal denture bases made from various
      plastic materials.
AB  - PURPOSE: The aim of the study was to compare the mechanical strength of palatal
      denture bases made from various plastic materials. MATERIALS AND METHODS: A form
      and models of an edentulous jaw (Frasaco) were used in the study. The denture
      bases were made from Zhermacryl H Plus and SR Ivocap Plus (both acrylic resins)
      and the polyurethane Microbase. Five samples were fabricated for each of the
      studied polymers. The fracture tests were carried out on a universal testing
      machine (Hounsfield H5KS). RESULTS: The highest fracture values were assessed on
      Ivocap specimens. The indicated differences between acrylic resin specimens made
      of Ivocap and Zhermacryl were not statistically significant. In turn, the
      differences shown between 2 acrylic resin palatal denture bases and the Microbase
      were statistically significant (P < .05). CONCLUSION: In this study, samples made
      from an alternative denture base polymer showed poorer mechanical strength as
      compared with those made of polymethylmethacrylate.

PMID- 16602371
TI  - Cytotoxicity of hard chairside reline resins: effect of microwave irradiation and
      water bath postpolymerization treatments.
AB  - PURPOSE: To evaluate the influence of water bath and microwave postpolymerization
      treatments on the cytotoxicity of 6 hard reline acrylic resins. MATERIALS AND
      METHODS: The materials tested were Tokuso Rebase Fast (TR), Ufi Gel Hard (UGH),
      Duraliner II (D), Kooliner (K), New Truliner (NT), and Light Liner (LL). LL resin
      was additionally tested with an air-barrier coating (LLABC). Nine disks of each
      material (10 x 1 mm) were made and divided into 3 groups: group 1 (no
      postpolymerization treatment); group 2 (postpolymerization in microwave oven);
      group 3 (postpolymerization in water bath at 55 degrees C for 10 minutes). L929
      cells were cultured in 96-well plates and incubated for 24 hours in Eagle's
      medium. Eluates prepared from the disks or medium without disks (control)
      replaced the medium. Cytotoxicity was assessed by both dehydrogenase succinic
      activity (MTT) assay and incorporation of radioactive 3H-thymidine assay. Tests
      were carried out in quadruplicate and repeated twice. Differences between groups
      were determined by analysis of variance with Tukey multiple-comparison intervals
      (alpha = .05). RESULTS: For MTT assay, the postpolymerization treatments had no
      effect on the cytotoxicity of all materials (P > .05). For 3H-thymidine assay,
      the postpolymerization treatments significantly decreased the cytotoxicity of UGH
      (P < .05). The cytotoxicity of K, NT, LL, and LLABC increased after microwave
      irradiation (P < .05). TR, NT, and LLABC showed an increase in cytotoxicity after
      water bath (P < .05). CONCLUSION: When assessed by MTT assay, the cytotoxicity of
      the materials was not affected by postpolymerization treatments. 3H-Thymidine
      assay showed that the cytotoxicity of the resins was not improved by the
      postpolymerization treatments, with the exception of UGH.

PMID- 16602372
TI  - Microbial adherence to a nonprecious alloy after plasma nitriding process.
AB  - PURPOSE: To investigate the microbial adherence to the surfaces of a nonprecious
      metal alloy after plasma nitriding. MATERIALS AND METHODS: The plasma-nitriding
      process was performed to the surfaces of metals prepared from a nickel-chromium
      alloy. The microorganisms were labeled with technetium-99m. After the labeling
      procedure, 60 metal disks were treated with a microorganism for each use.
      RESULTS: The results revealed that the amount of adherence of all microorganisms
      on surfaces was changed by plasma-nitriding process; adherence decreased
      substantially (P < .05) and the differences in plasma nitriding time were not
      significant (P> .05) CONCLUSION: With the plasma-nitriding process, the surface
      properties of nonprecious metal alloys can be changed, leading to decreased
      microbial adherence.

PMID- 16602373
TI  - The influence of prior choices on current choice.
AB  - Three pigeons chose between random-interval (RI) and tandem, continuous
      reinforcement, fixed-interval (crf-FI) reinforcement schedules by pecking either
      of two keys. As long as a pigeon pecked on the RI key, both keys remained
      available. If a pigeon pecked on the crf-FI key, then the RI key became
      unavailable and the crf-FI timer began to time out. With this procedure, once the
      RI key was initially pecked, the prospective value of both alternatives remained
      constant regardless of time spent pecking on the RI key without reinforcement (RI
      waiting time). Despite this constancy, the rate at which pigeons switched from
      the RI to the crf-FI decreased sharply as RI waiting time increased. That is,
      prior choices influenced current choice-an exercise effect. It is argued that
      such influence (independent of reinforcement contingencies) may serve as a sunk
      cost commitment device in self-control situations. In a second experiment,
      extinction was programmed if RI waiting time exceeded a certain value. Rate of
      switching to the crf-FI first decreased and then increased as the extinction
      point approached, showing sensitivity to both prior choices and reinforcement
      contingencies. In a third experiment, crf-FI availability was limited to a brief
      window during the RI waiting time. When constrained in this way, switching
      occurred at a high rate regardless of when, during the RI waiting time, the crf
      FI became available.

PMID- 16602374
TI  - Resistance to extinction following variable-interval reinforcement: reinforcer
      rate and amount.
AB  - Rats obtained food-pellet reinforcers by nose poking a lighted key. Experiment 1
      examined resistance to extinction following single-schedule training with
      different variable-interval schedules, ranging from a mean interval of 16 min to
      0.25 min. That is, for each schedule, the rats received 20 consecutive daily
      baseline sessions and then a session of extinction (i.e., no reinforcers).
      Resistance to extinction (decline in response rate relative to baseline) was
      negatively related to the rate of reinforcers obtained during baseline, a
      relation analogous to the partial-reinforcement-extinction effect. A positive
      relation between these variables emerged, however, when the unit of extinction
      was taken as the mean interreinforcer interval that had been in effect during
      training (i.e., as an omitted reinforcer during extinction). In a second
      experiment, rats received blocks of training sessions, all with the same variable
      interval schedule but with a reinforcer of four pellets for some blocks and one
      pellet for others. Resistance to extinction was greater following training with
      the larger (four pellets) than with the smaller (one pellet) reinforcer. Taken
      together, these results support the principle that greater reinforcement during
      training (e.g., higher rate or larger amount) engenders greater resistance to
      extinction even when the different conditions of reinforcement are varied between
      blocks of sessions.

PMID- 16602375
TI  - Discriminability and sensitivity to reinforcer magnitude in a detection task.
AB  - Three pigeons discriminated between two sample stimuli (intensities of red
      light). The difficulty of the discrimination was varied over four levels. At each
      level, the relative reinforcer magnitude for the two correct responses was varied
      across conditions, and the reinforcer rates were equal. Within levels,
      discriminability between the sample stimuli did not change systematically as
      reinforcer magnitude varied. Across levels, the sensitivity of behavior to
      changes in the reinforcer-magnitude ratio decreased as the discriminability
      between the sample stimuli increased. Subsequent analysis showed that this
      relation was limited to performance following only one of the sample stimuli, the
      dim red light that remained constant across all conditions. Extant behavioral
      models of signal detection cannot easily accommodate these results.

PMID- 16602376
TI  - Feedback functions, optimization, and the relation of response rate to reinforcer
      rate.
AB  - The present experiment arranged a series of inverted U-shaped feedback functions
      relating reinforcer rate to response rate to test whether responding was
      consistent with an optimization account or with a one-to-one relation of response
      rate to reinforcer rate such as linear system theory's rate equation or
      Herrnstein's hyperbola. Reinforcer rate was arranged according to a quadratic
      equation with a maximum at a unique response rate. The experiment consisted of
      two phases, during which 6 Long Evans rats lever pressed for food. In the first
      phase of the experiment, the rats responded on six fixed-interval-plus-quadratic
      feedback schedules, and in the second phase the rats responded on three variable
      interval-plus-quadratic-feedback schedules. Responding in both phases was
      inconsistent with a one-to-one relation of response rate to reinforcer rate.
      Instead, different response rates were obtained at equivalent reinforcer rates.
      Responding did vary directly with the vertex of the feedback function in both
      phases, a finding consistent with optimization of reinforcer rate. The present
      results suggest that the feedback function relating reinforcer rate to response
      rate imposed by a reinforcement schedule can be an important determinant of
      behavior. Furthermore, the present experiment illustrates the benefit of
      arranging feedback functions to investigate assumptions about the variables that
      control schedule performance.

PMID- 16602377
TI  - Replacing relative reinforcing efficacy with behavioral economic demand curves.
AB  - Relative reinforcing efficacy refers to the behavior-strengthening or maintaining
      property of a reinforcer when compared to that of another reinforcer. Traditional
      measures of relative reinforcing efficacy sometimes have led to discordant
      results across and within studies. By contrast, previous investigations have
      found traditional measures to be congruent with behavioral economic measures,
      which provide a framework for integrating the discordant results. This study
      tested whether the previously demonstrated congruence between traditional
      relative reinforcing efficacy measures and behavioral economic demand curve
      measures is sufficiently robust to persist when demand for one reinforcer is
      altered. Cigarette smokers pulled plungers for cigarettes or two magnitudes of
      money on progressive-ratio schedules that increased the response requirement
      across sessions. Demand for the two different reinforcers was assessed in single
      schedule and concurrent-schedule sessions. Demand curve measures Pmax and Omax
      correlated significantly with traditional measures of breakpoint and peak
      response rate, respectively. Relative locations of demand curves for money and
      cigarettes under single schedules predicted preference in concurrent schedules in
      most cases. Although measures of relative reinforcing efficacy for money changed
      with money magnitude, the congruence between traditional and behavioral economic
      measures remained intact. This robust congruence supports the proposal that
      demand curves should replace measures of relative reinforcing efficacy. The
      demand curve analysis illustrates why concordance between traditional measures is
      expected under some experimental conditions but not others.

PMID- 16602378
TI  - Second-order schedules of token reinforcement with pigeons: implications for unit
      price.
AB  - Four pigeons were exposed to second-order schedules of token reinforcement, with
      stimulus lights serving as token reinforcers. Tokens were earned according to a
      fixed-ratio (token-production) schedule, with the opportunity to exchange tokens
      for food (exchange period) occurring after a fixed number had been produced
      (exchange-production ratio). The token-production and exchange-production ratios
      were manipulated systematically across conditions. Response rates varied
      inversely with the token-production ratio at each exchange-production ratio.
      Response rates also varied inversely with the exchange-production ratio at each
      token-production ratio, particularly at the higher token-production ratios. At
      higher token-production and exchange-production ratios, response rates increased
      in token-production segments closer to exchange periods and food. Some conditions
      were conducted in a closed economy, in which the pigeons earned all their daily
      ration of food within the session. Relative to comparable open-economy
      conditions, response rates in the closed economy were less affected by changes in
      token-production ratio, resulting in higher levels of food intake and body
      weight. Some of the results are consistent with the economic concept of unit
      price, a cost-benefit ratio comprised of responses per unit of food delivery, but
      most are well accounted for by a consideration of the number of responses
      required to produce exchange periods, without regard to the amount of
      reinforcement available during those exchange periods.

PMID- 16602379
TI  - Experimental control of nodality via equal presentations of conditional
      discriminations in different equivalence protocols under speed and no-speed
      conditions.
AB  - A within-participant comparison of simple-to-complex, complex-to-simple, and
      simultaneous protocols was conducted establishing different sets of three 7
      member equivalence classes for 4 undergraduate students. The protocols were
      implemented under either accuracy-only or accuracy-plus-speed conditions while
      keeping number of presentations of training and testing trials equal. The results
      partially support previous reports of differential effects on acquisition, with
      participants completing more blocks in training under the simultaneous than the
      complex-to-simple and the simple-to-complex protocols. Across the protocols,
      however, the number of trials completed to criterion did not vary systematically.
      More important, response speed and accuracy did not decrease as a function of
      nodal number, with or without the speed contingency, or under any protocol. The
      latter results challenge the generality of previous reports of the nodality
      effect and the notion of "relatedness" of equivalence-class members, and support
      a reinforcement-contingency, instead of a structural, perspective on equivalence
      class formation.

PMID- 16602380
TI  - About Skinner and time: behavior-analytic contributions to research on animal
      timing.
AB  - The article discusses two important influences of B. F. Skinner, and later
      workers in the behavior-analytic tradition, on the study of animal timing. The
      first influence is methodological, and is traced from the invention of schedules
      imposing temporal constraints or periodicities on animals in The Behavior of
      Organisms, through the rate differentiation procedures of Schedules of
      Reinforcement, to modern temporal psychophysics in animals. The second influence
      has been the development of accounts of animal timing that have tried to avoid
      reference to internal processes of a cognitive sort, in particular internal clock
      mechanisms. Skinner's early discussion of temporal control is first reviewed, and
      then three recent theories-Killeen & Fetterman's (1988) Behavioral Theory of
      Timing; Machado's (1997) Learning to Time; and Dragoi, Staddon, Palmer, &
      Buhusi's (2003) Adaptive Timer Model-are discussed and evaluated.

PMID- 16602381
TI  - An evaluation of the value of choice with preschool children.
AB  - The current study examined the reinforcing effects of choosing among alternatives
      in a four-part evaluation. In the first study, initial-link responses in a
      concurrent-chains arrangement resulted in access to terminal links in which the
      completion of an academic task resulted in (a) the choice of a reinforcer
      (choice), (b) the delivery of an identical reinforcer (no choice), or (c) no
      material reinforcer (control). Three patterns of responding emerged: persistent
      preference for choice (3 participants); initial preference for choice, which did
      not persist (2 participants); and preference for no choice (1 participant).
      Additional evaluations determined if preference for choice could be enhanced
      (Study 2) or established (Study 3) by including more stimuli from which to
      choose. Choice-link selections systematically increased for all participants when
      more items were available from which to choose. Study 4 identified the precise
      value of the opportunity to choose by progressively increasing the response
      requirement during the choice terminal links for 3 children and determining the
      point at which these children stopped selecting the choice link. All children
      continued to select the choice link even when the work required in the choice
      link was much greater than that arranged in the no-choice link.

PMID- 16602382
TI  - Establishment of mands following tact training as a function of reinforcer
      strength.
AB  - We examined some conditions under which a response acquired as a tact might
      facilitate the establishment of a mand. We taught 3 participants with
      developmental disabilities to tact the items ranked highest and lowest in a
      preference assessment and subsequently tested to see if the responses occurred as
      mands. All participants manded for the highly preferred item but rarely manded
      for the nonpreferred item. These results indicate that, although tact and mand
      functions are different, conditions can be created to facilitate transfer from
      the former to the latter. Implications for communication training are discussed.

PMID- 16602383
TI  - A preliminary evaluation of two behavioral skills training procedures for
      teaching abduction-prevention skills to schoolchildren.
AB  - Although child abduction is a low-rate event, it presents a serious threat to the
      safety of children. The victims of child abduction face the threat of physical
      and emotional injury, sexual abuse, and death. Previous research has shown that
      behavioral skills training (BST) is effective in teaching children abduction
      prevention skills, although not all children learn the skills. This study
      compared BST only to BST with an added in situ training component to teach
      abduction-prevention skills in a small-group format to schoolchildren. Results
      showed that both programs were effective in teaching abduction-prevention skills.
      In addition, the scores for the group that received in situ training were
      significantly higher than scores for the group that received BST alone at the 3
      month follow-up assessment.

PMID- 16602384
TI  - Establishing and maintaining treatment effects with less intrusive consequences
      via a pairing procedure.
AB  - The generality and long-term maintenance of a pairing procedure designed to
      improve the efficacy of less intrusive procedures were evaluated for the
      treatment of problem behavior maintained by automatic reinforcement exhibited by
      2 individuals with developmental disabilities. Results suggested that a less
      intrusive procedure could be established as a conditioned punisher by pairing it
      with an effective punisher contingent on problem behavior. Generalization across
      multiple therapists was demonstrated for both participants. However,
      generalization to another setting was not achieved for 1 participant until
      pairing was conducted in the second setting. Long-term maintenance was observed
      with 1 participant in the absence of further pairing trials. Maintenance via
      intermittent pairing trials was successful for the other participant.

PMID- 16602385
TI  - A comparison of interteaching and lecture in the college classroom.
AB  - Interteaching is a new method of classroom instruction that is based on
      behavioral principles but offers more flexibility than other behaviorally based
      methods. We examined the effectiveness of interteaching relative to a traditional
      form of classroom instruction-the lecture. In Study 1, participants in a graduate
      course in special education took short quizzes after alternating conditions of
      interteaching and lecture. Quiz scores following interteaching were higher than
      quiz scores following lecture, although both methods improved performance
      relative to pretest measures. In Study 2, we also alternated interteaching and
      lecture but counterbalanced the conditions across two sections of an
      undergraduate research methods class. After each unit of information,
      participants from both sections took the same test. Again, test scores following
      interteaching were higher than test scores following lecture. In addition,
      students correctly answered more interteaching-based questions than lecture-based
      questions on a cumulative final test. In both studies, the majority of students
      reported a preference for interteaching relative to traditional lecture. In sum,
      the results suggest that interteaching may be an effective alternative to
      traditional lecture-based methods of instruction.

PMID- 16602386
TI  - Evaluating the relative effects of feedback and contingent money for staff
      training of stimulus preference assessments.
AB  - Performance feedback has facilitated the acquisition and maintenance of a wide
      range of behaviors (e.g., health-care routines, seat-belt use). Most researchers
      have attributed the effectiveness of performance feedback to (a) its
      discriminative functions, (b) its reinforcing functions, or (c) the combination
      of the two. In this study, we attempted to evaluate the relative contributions of
      the discriminative and reinforcing functions of performance feedback by comparing
      a condition in which the discriminative functions were maximized and the
      reinforcing functions were minimized (i.e., performance-specific instructions
      without contingent money) with one in which the reinforcing functions were
      maximized and the discriminative functions were minimized (i.e., contingent money
      with no performance-specific instructions). We compared the effects of these two
      conditions on the acquisition of skills involved in conducting two commonly used
      preference assessments. Results showed that acquisition of these skills occurred
      primarily in the condition with performance-specific instruction without
      contingent money, suggesting that the delivery of performance-specific
      instructions was critical to skill acquisition, whereas the delivery of
      contingent money had little effect.

PMID- 16602387
TI  - A descriptive assessment of instruction-based interactions in the preschool
      classroom.
AB  - The current study describes preschool teacher-child interactions during several
      commonly scheduled classroom activities in which teachers deliver instructions.
      An observation system was developed that incorporated measurement of evidence
      based compliance strategies and included the types of instructions delivered
      (e.g., integral or deficient directives, embedded directives, "do" or "don't"
      commands), the children's behavior with respect to the instructions (e.g.,
      compliance, noncompliance, active avoidance, problem behavior), and the
      differential responses of the teacher to the child's behavior following an
      instruction (e.g., appropriate or inappropriate provision of attention and
      escape). After 4 classroom teachers were observed at least five times in each of
      five target activities, simple and conditional probabilities were calculated.
      Results indicated that (a) the frequency of instruction and probability of
      compliance varied as a function of activity type, (b) "do" commands and directive
      prompts were delivered almost to the exclusion of "don't" commands and
      nondirective prompts, (c) the likelihood of compliance was highest following an
      embedded or an integral directive prompt, and (d) although putative social
      reinforcers were more likely to follow noncompliance than compliance and were
      highly likely following problem behavior, compliance occurred over twice as much
      as noncompliance, and problem behavior during instructions was very low.
      Implications for using descriptive assessments for understanding and improving
      teacher-child interactions in the preschool classroom are discussed.

PMID- 16602388
TI  - Enhancing job-site training of supported workers with autism: a reemphasis on
      simulation.
AB  - Currently recommended practice in supported work emphasizes training job skills
      to workers with severe disabilities while on the job. Early behavioral research
      indicated that skills needed in natural environments could also be trained in
      simulated settings. We compared job-site plus simulation training for teaching
      job skills to supported workers with autism to provision of training exclusively
      on the job. Job-site training occurred in a small publishing company during the
      regular work routine, and simulation training occurred in an adult education site
      for people with severe disabilities. Two pairs of workers received training on
      two job skills; one skill was trained at the job site and the other was trained
      using job-site plus simulation training. Results indicated that for 3 of the 4
      comparisons, job-site plus simulation training resulted in a higher level of
      skill or more rapid skill acquisition than did job-site-only training. Results
      suggested that job-site training, the assumed best practice for teaching
      vocational skills, is likely to be more effective if supplemented with simulation
      training. Directions for future research include expanding applications of
      behavioral technologies to other aspects of the current support paradigm.

PMID- 16602389
TI  - Brief functional analysis and treatment of tantrums associated with transitions
      in preschool children.
AB  - A brief functional analysis was used to examine the influence of termination of
      prechange activities and initiation of postchange activitieson tantrums exhibited
      by 2 preschool children. For 1 participant, tantrums were maintained by access to
      certain (pretransition) activities. For a 2nd participant, tantrums were
      maintained by avoidance of certain task initiations. Although advance notice of
      an upcoming transition was ineffective, differential reinforcement of other
      behavior plus extinction reduced tantrums for both participants.

PMID- 16602390
TI  - A preliminary analysis of teaching improvisation with the picture exchange
      communication system to children with autism.
AB  - Two young boys with autism who used the picture exchange communication system
      were taught to solve problems (improvise) by using descriptors (functions,
      colors, and shapes) to request desired items for which specific pictures were
      unavailable. The results of a multiple baseline across descriptors showed that
      training increased the number of improvised requests, and that these skills
      generalized to novel items, and across settings and listeners in the natural
      environment.

PMID- 16602391
TI  - The effects of prompting and feedback on drivers' stopping at stop signs.
AB  - Complete stops at a high-traffic intersection on the campus of a public
      university were increased with a prompting and consequence intervention. Data
      were collected at two opposing stop signs (Stop A and Stop B); however, the
      intervention was implemented only at Stop A. During the intervention, a volunteer
      stood next to Stop A holding a poster that read, "Please Stop--I Care," with
      "Thank You For Stopping" on the reverse side. The poster was held by the
      volunteer so that drivers approaching Stop A could read the sign. Drivers
      approaching Stop B could see the volunteer but could not read the sign. When
      vehicles approaching Stop A made a complete stop, the volunteer flashed the
      "thank you" side of the poster to the driver. The strategy was evaluated using a
      multielement design. The intervention increased stops completed at Stop A from a
      baseline average of 13% to an intervention average of 52%. Stop B also showed
      improved stopping, from a baseline average of 6% to an intervention average of
      28%. Data showed no relation between complete stops made and the drivers' use of
      turn signals and safety belts.

PMID- 16602392
TI  - Effects of guided notes versus completed notes during lectures on college
      students' quiz performance.
AB  - We compared the effects of guided lecture notes versus completed lecture notes on
      pre- to postlecture improvements in quiz performance across two sections of a
      college course. The results of a counterbalanced multielement design did not
      reveal consistent differences between the two note formats on students' mean quiz
      scores. However, fewer errors occurred on complex (analysis-level) quiz questions
      in the guided notes condition than in the completed notes condition.

PMID- 16602393
TI  - The impact of high- and low-preference stimuli on vocational and academic
      performances of youths with severe disabilities.
AB  - Pictorial and tangible paired-stimulus preference assessments were compared with
      4 adolescents with developmental disabilities. In the tangible assessment, two
      stimuli were placed in front of the participant on each trial; in the pictorial
      assessment, two line drawings were placed in front of the participant on each
      trial. Approach responses were recorded for each assessment. The assessments
      generated similar preference hierarchies for all participants. Reinforcer
      assessments confirmed that response rates were higher when access to high
      preference items was available than when low-preference items were available.
      Implications for assessing preferences and selecting items to be used in training
      programs are discussed.

PMID- 16602394
TI  - Toward an empirical method for identifying matched stimulation for automatically
      reinforced behavior: a preliminary investigation.
AB  - The effects of noncontingent matched stimulation (NMS) and response blocking on a
      boy's stereotypic behavior were evaluated using a multiple schedule that
      contained three 15-min components (preintervention, intervention, and
      postintervention). Results showed that stereotypy was always higher after
      response blocking than before response blocking and was always lower after NMS
      than before NMS. These results suggest that response blocking may have produced
      deprivation for the product of stereotypy and that NMS may have provided
      stimulation that was similar to the product of stereotypy.

PMID- 16602396
TI  - Schisms in the tobacco control movement (part 1).

PMID- 16602395
TI  - Analysis and treatment of problem behavior evoked by music.
AB  - The present study investigated the effects of differential negative reinforcement
      of other behavior (DNRO) on problem behavior evoked by music in a 7-year-old
      child with pervasive developmental disorder. Following an auditory stimulus
      assessment, DNRO was used to reduce problem behavior to near-zero levels. Results
      are discussed in terms of identifying establishing operations to govern treatment
      options and the use of negative reinforcement when arbitrarily imposed positive
      reinforcers do not compete with escape from auditory stimulation.

PMID- 16602397
TI  - The assessment and management of patients with acute asthma.
AB  - Acute asthma is a common medical emergency that is often poorly assessed and
      managed. Initial evaluation should include a review of historical factors for
      identifying high risk patients; appropriate evaluation of the current
      exacerbation, including an objective assessment of airflow obstruction; and, in
      parallel, initiation of therapy with controlled oxygen therapy, regular
      bronchodilator therapy and, in most cases, systemic corticosteroids. There is no
      benefit in using intravenous (IV) corticosteroids--a single 50 mg oral dose is
      appropriate. Although there is no significant additional bronchodilator effect
      with the use of ipratropium bromide or IV magnesium, both modalities have been
      shown to reduce hospitalisations for moderate to severe exacerbations. There is
      no role for the routine use of IV aminophylline or beta (beta) agonists in
      patients presenting with acute asthma. Patients who achieve 60% of their
      predicted peak expiratory flow (PEF) or 1 sec forced expiratory volume (FEV1) or
      best can usually be safely discharged. The exacerbation should be taken as an
      opportunity to review how a patient responded to the particular exacerbation.
      Were they on appropriate anti-inflammatory therapy? Did they modify the dose of
      therapy early in the exacerbation? Did they have an action plan? Such
      deficiencies can usually be managed by facilitated referral to a specialist
      clinic that ideally has an asthma education programme. The need for long-term
      anti-inflammatory therapy can be reviewed at this time as well as the potential
      incremental benefit of the addition of add-on therapy, most likely the use of a
      long-acting beta agonist.

PMID- 16602398
TI  - Treating the patient with asthma.
AB  - Treatment of patients with asthma, although straight-forward, is a challenge. The
      treatment is prolonged, often for life, and must be taken regularly. For low
      income countries, the treatment must be efficient and feasible. Two drugs are
      indicated: one to reduce the inflammation and one to relieve the airflow
      obstruction. The treatment and its goals need to be explained to the patient with
      asthma and to family members, as the success of treatment is dependent on their
      cooperation. The medications that reduce inflammation are corticosteroids.
      Inhaled beclomethasone 250 microg per puff is indicated for every patient who has
      persistent asthma. The medication recommended for relief of airflow obstruction
      is inhaled salbutamol/100 microg per puff. A four-step approach to treatment is
      indicated, starting with the dose of medication indicated by the degree of
      severity of the asthma, and periodically adjusted. When the condition improves
      and remains stable for at least 3 months, the dose of medication may be reduced
      to fit the grade of severity assessed at that time. In the event the condition
      worsens, the treatment is increased stepwise. This approach to treatment has
      every promise to improve the life and health of patients with asthma.

PMID- 16602399
TI  - Prevalence and trend of self-reported asthma and other allergic disease symptoms
      in Morocco: ISAAC phase I and III.
AB  - BACKGROUND: The prevalence of asthma and other allergic diseases is increasing in
      many parts of the world. OBJECTIVE: To determine the prevalence of asthma,
      rhinoconjunctivitis and skin allergy symptoms in Morocco as part of the
      International Study of Asthma and Allergic Diseases in Children (ISAAC). METHODS:
      The survey was conducted using the standardised method of ISAAC Phase III in four
      centres in Morocco-Casablanca, Marrakech, Ben Slimane and Boulmane-with
      respectively 1777, 1689, 1008 and 1254 13-14-year-old schoolchildren
      participating. A comparison of the results with ISAAC Phase I was carried out in
      two centres. RESULTS: The prevalence of self-reported symptoms of wheeze in the
      last 12 months (6.4-16.2%), nasal symptoms (27.9-52.8%), rhinoconjonctivitis (8.8
      28%) and eczema (13.3-20.2%) varied between centres, and were highest in
      Casablanca, the largest city in Morocco. Significant increases in almost all
      symptoms were found in the two centres of Casablanca and Marrakech between ISAAC
      Phase I and Phase III. CONCLUSION: Morocco could be classified as a country with
      an intermediate burden of asthma (between 10% and 15%) and other allergic
      disorders. The prevalence of these symptoms has increased in the past 5 years.

PMID- 16602400
TI  - HIV infection and tobacco smoking behaviour: prospects for prevention? ANRS CO3
      Aquitaine Cohort, 2002.
AB  - OBJECTIVE: To provide up-to-date and covariate-specific estimates on tobacco
      smoking prevalence in a representative cohort of French human immunodeficiency
      virus (HIV) 1 infected patients in 2002. DESIGN: We conducted a cross-sectional
      analysis of the Aquitaine Cohort of HIV-infected patients. A logistic regression
      model was used to estimate associations between regular tobacco smoking and sex,
      age, HIV transmission categories, duration and immuno-virological status of HIV
      infection and duration of antiretroviral therapy. Smoking prevalence estimates
      were compared with the general French population values after stratification on
      age and sex. RESULTS: Among 2036 patients included in the analysis, 51% were
      regular smokers (95%CI 49-53). Smoking prevalence was significantly higher with
      younger age (OR 1.7 among those < or = 45 years of age), among injecting drug
      users (OR 4.3), among those whose infection was not controlled (OR 1.2) and those
      whose HIV infection had been diagnosed for > or = 5 years (OR 1.5). The main
      difference with the general population was the peak smoking prevalence among HIV
      positive patients infected through injecting drug use. CONCLUSIONS: HIV-infected
      patients are highly exposed to tobacco smoking, which is implicated in multiple
      conditions occurring in the course of HIV infection. Adapted smoking cessation
      programmes should become one of the priorities of the medical care of HIV
      infected individuals.

PMID- 16602401
TI  - Assessing occupational exposure as risk for tuberculous infection at a teaching
      hospital in Sao Paulo, Brazil.
AB  - OBJECTIVE: To determine the risk for TB infection among nurses exposed to TB
      patients and non-exposed employees, and to evaluate associated aspects to
      initiate TB prevention in a teaching hospital in Brazil. DESIGN: A cross
      sectional tuberculin skin test (TST) survey and assessment questionnaire of 169
      nurses exposed to patients (exposed group [EG]) and 164 administrative employees
      (comparative group [CG]). RESULTS: The prevalence of positive TST was 59.7% in
      the EG and 53.7% in the CG (P = 0.26). Univariate analysis revealed, in the CG,
      association of TST positivity with BCG scar (P = 0.002), and, in the EG, with
      male sex (P = 0.02) and working at that hospital for >2 years (P < 0.001). On
      multivariate analysis, male sex (P = 0.0444), working at the institution for >2
      years (P < 0.0001) and BCG scar (P = 0.0004) were associated with positive TST,
      while occupational exposure was not. CONCLUSIONS: The results suggest that all
      health care workers should be evaluated in an institutional TB prevention
      programme because community exposure to TB and BCG vaccination may have
      influenced TST positivity in the studied population.

PMID- 16602402
TI  - Health care seeking behaviour for tuberculosis symptoms in Kiev City, Ukraine.
AB  - SETTING: Tuberculosis (TB) doctors in Kiev City have the impression that TB
      patients often present with advanced TB disease, and the mortality rate among TB
      patients is high. Delay in seeking health care may explain these observations.
      OBJECTIVE: To assess the magnitude of patient delay and evaluate risk factors for
      delay. DESIGN: We included 190 newly diagnosed pulmonary TB patients. For each
      patient, information was gathered through interviews and from the medical
      records. RESULTS: The median time between the start of symptoms and the first
      visit to a health care provider (patient delay) was 30.0 days. Individuals
      reporting unemployment, cough or loss of weight before seeking health care had a
      longer patient delay. The same applies to individuals with the risk factors
      homelessness, joblessness or alcohol abuse. The main reasons for delay among
      those who presented late were 'thought symptoms would go away' and 'symptoms not
      considered serious'. CONCLUSION: For most TB patients, the time between start of
      symptoms and first health care seeking action was acceptable. Long patient delay
      was reported by individuals who were homeless, jobless or abused alcohol.
      Specific activities will have most effect if they are targeted at these
      vulnerable and difficult to reach groups.

PMID- 16602403
TI  - High prevalence of hepatitis C virus but not HIV co-infection among patients with
      tuberculosis in Georgia.
AB  - SETTING: Tuberculosis (TB) and hepatitis C virus (HCV) infection have emerged as
      major public health problems in former Soviet republics. OBJECTIVE: To determine
      the prevalence and risk factors for the human immunodeficiency virus (HIV) and
      HCV co-infection among patients with TB in Georgia, a cross-sectional study was
      carried out at hospitals in four Georgian cities. RESULTS: Of 272 hospitalized
      patients with TB, 61 (22%) were found to be HCV-seropositive and three (1%) were
      HIV-seropositive. The median age of those with TB was 35 years (range 18-74
      years); 74% were male. In multivariate analysis, risk factors for HCV co
      infection included previous incarceration (OR 4.6, 95%CI 1.9-10.8), history of
      receiving a tattoo (OR 2.6, 95%CI 1.2-5.7), previous diagnosis of a sexually
      transmitted infection (OR 7.2, 95%CI 1.4-37.8), and age 26-45 years (OR 2.1,
      95%CI 1.0-4.6). CONCLUSION: HCV co-infection was common among hospitalized
      patients with TB in Georgia. Incarceration and receiving a tattoo, a common
      practice among inmates in Georgian and former Soviet correctional facilities,
      were important independent risk factors associated with HCV infection among those
      with TB. Further studies are needed to assess the impact of the high prevalence
      of HCV co-infection on treatment outcomes, including tolerability and risk of
      anti-tuberculosis drug induced hepatotoxicity.

PMID- 16602404
TI  - Treatment outcomes in an integrated civilian and prison MDR-TB treatment program
      in Russia.
AB  - SETTING: Multidrug-resistant tuberculosis (MDR-TB) is a major problem in
      countries of the former Soviet Union in both the civilian and prison sectors.
      OBJECTIVE: To evaluate outcomes of the MDR-TB treatment program (DOTS-Plus) in
      Tomsk, Russia. DESIGN: Retrospective case series of all patients enrolled in this
      program between 10 September 2000 and 10 September 2002. The program involves
      both the civilian and penitentiary TB services in Tomsk. Poor treatment outcome
      was defined as death, default and treatment failure. RESULTS: Among the 244
      patients who received treatment, 77% were cured, 5% died, 7% failed, and 12%
      defaulted. In a multivariable analysis, alcohol consumption during treatment and
      the presence of both cavitary and bilateral disease were found to be the
      strongest predictors of poor treatment outcome. CONCLUSIONS: The integration of
      civilian and penitentiary TB services in the Tomsk MDR-TB treatment program has
      resulted in high cure rates and low rates of default. However, alcohol use among
      patients with MDR-TB is associated with poor treatment outcomes. Better
      understanding and programmatic alcohol interventions are needed if large-scale
      treatment of MDR-TB is to be successful in areas with high rates of alcohol use
      disorders.

PMID- 16602405
TI  - Multidrug-resistant tuberculosis without HIV infection: success with
      individualised therapy.
AB  - OBJECTIVE: To evaluate the results of the treatment of non-HIV-infected multidrug
      resistant tuberculosis (MDR-TB) patients admitted to a tuberculosis unit in a
      reference centre between June 1998 and December 2000. RESULTS: Twenty-five
      patients were studied (23 men). Empirical treatment was selected according to
      drugs previously used and adjusted according to in vitro test results. Patients
      had previously received an average of 5.5 drugs and were resistant to an average
      of 4.7 drugs. They were treated with a median number of four drugs (an injectable
      drug plus three oral drugs) for a median of 18 months. Ofloxacin and cycloserine
      was used in 17 cases (68%), ethionamide/prothionamide in 18 (72%) and para
      aminosalicylic acid in 12 patients (48%). Psychological support and counselling
      was provided. Two patients required surgery. Globally, 21 patients (84%) met cure
      criteria. After a 24-month follow-up, none of the 21 patients who successfully
      completed treatment presented relapse or death. CONCLUSION: MDR-TB is a curable
      disease in non-HIV-infected patients. Individualised treatment regimens should be
      based on treatment history and the study of in vitro susceptibility and by
      promoting a relationship with the patient that makes adherence to treatment
      easier and minimises side effects.

PMID- 16602406
TI  - Undetected burden of tuberculosis in a low-prevalence area.
AB  - SETTING: Under-ascertainment and under-reporting of tuberculosis (TB) hampers
      surveillance and control. Case detection is improved by record linkage of case
      registers and under-reporting can be estimated by capture-recapture (CR)
      analysis. OBJECTIVES: To assess the completeness of the TB registration systems
      and estimation of TB incidence and under-reporting in the Piedmont Region of
      Italy in 2001. METHODS: Record linkage of the 'physician notification system',
      the TB laboratory register and the hospital records register, and subsequent
      three-sample CR analysis. RESULTS: Record linkage identified 657 TB cases; CR
      analysis estimated 47 (95%CI 31-71) unrecorded cases. Under-reporting of the
      'physician notification system' was estimated at 21% (95%CI 20-23). The overall
      estimated TB incidence rate was 16.7 cases per 100000 population (95%CI 16.3
      17.3), varying according to the subset investigated: 12.7 for individuals from
      low TB prevalence countries and 214.1 for immigrants from high TB prevalence
      countries; 13.1 and 25.8 for persons aged < and > or = 60 years, respectively;
      and 32.1 in Turin, the regional capital and 10.8 in the rest of the region.
      CONCLUSIONS: When multiple recording systems are available, record linkage and CR
      analysis can be used to assess TB incidence and the completeness of different
      registers, contributing to a more accurate surveillance of local TB epidemiology.

PMID- 16602407
TI  - Patient and health system delays in the diagnosis of tuberculosis in Southern
      Thailand after health care reform.
AB  - SETTING: Seven public hospitals in a southern province of Thailand. OBJECTIVES:
      To measure delays in tuberculosis (TB) diagnosis and to examine the factors
      associated with these delays, with special focus on the effect of drug store
      utilisation and health insurance coverage on patient delay. DESIGN: A total of
      202 newly diagnosed smear-positive and smear-negative pulmonary TB patients were
      interviewed using a structured questionnaire. RESULTS: The median patient, health
      system and total delay were 4.4, 2.8 and 9.4 weeks, respectively. Risk factors
      for patient delay were age 31-60 years, having mild illness, previous similar
      symptoms and first presenting to non-qualified providers. Health insurance was
      not associated with a shorter patient delay. Health system delay was significant
      longer for patients with health insurance and first presenting to low-level
      public health facility (i.e., community hospital, health centre, primary care
      unit or private clinic/hospital). CONCLUSIONS: The public should be informed how
      to recognise TB symptoms to shorten patient delay. The Thai National Tuberculosis
      Control Programme needs to supervise the private health sector, including drug
      stores, for better TB control. Drug store personnel need to be trained to
      recognise and refer TB suspects. The capacity of low-level public health
      facilities and private doctors in TB diagnosis needs improvement. A proper
      referral system should be developed.

PMID- 16602408
TI  - Predictors of development and outcome in patients with acute respiratory distress
      syndrome due to tuberculosis.
AB  - OBJECTIVE: To study the predictors of development and determinants of outcome in
      patients with acute respiratory distress syndrome (ARDS) due to tuberculosis
      (TB). METHODS: Retrospective case-control study of demographic, clinical and
      laboratory data of hospitalised adult patients with active TB. RESULTS: Of 2733
      TB patients treated during 1980-2003, 29 (1.06%; 1.21 patients/year; mean age
      31.6 +/- 10.9 years; 16 males) developed ARDS (cases). Seven had pulmonary TB and
      22 had miliary TB (MTB); 298 (mean age 32.0 +/- 14.2 years; 110 males) who did
      not develop ARDS constituted controls. Presence of MTB (OR 4.6, 95%CI 1.2-17.8; P
      = 0.02), duration of illness beyond 30 days at presentation (OR 177.9, 95%CI 39
      811.7; P < 0.001), absolute lymphocyte count < 1625/ mm3 (OR 4.5, 95%CI 1.1-19.3;
      P = 0.04) and serum ALT > 100 IU (OR 15.7, 95%CI 3.0-81.1, P < 0.001) were
      independent predictors of ARDS development. Twelve cases died (41.4%). Patients
      with APACHE II score >18; those with APACHE II score <18 in the presence of
      hyponatraemia and PaO2/FIO2 ratio <108.5 were likely to die. CONCLUSIONS: In
      patients with TB, prolonged illness, MTB, absolute lymphocytopaenia and elevated
      ALT are independently associated with ARDS development. APACHE II score, serum
      sodium and PaO2/FIO2 ratio are determinants of outcome.

PMID- 16602409
TI  - Are patients who present spontaneously with PTB symptoms to the health services
      in Burkina Faso well managed?
AB  - SETTING: Six health districts selected from a total of 53 in Burkina Faso.
      OBJECTIVE: To evaluate the performance of the health services in identifying
      infectious pulmonary tuberculosis (PTB) cases in Burkina Faso. DESIGN:
      Retrospective review of initial consultation registers in the first level health
      centres and the laboratory and treatment registers kept at the Centres for TB
      Diagnosis and Treatment (CDTs) in 2001. RESULTS: The rate of detection of sputum
      positive cases of PTB was 11.7 cases per 100000 population. Cough was the reason
      for consulting for 10.6% of 248,730 adults; 1.1% had chronic cough. Among
      patients with chronic cough, 66% had been referred for smear microscopy, 69.7% of
      whom were registered at the CDT to which they were referred. A positive diagnosis
      was made in 22.5% of the suspects referred and traced to the CDT. Among those
      with a positive diagnosis, 87.1% were put on treatment in the same CDT.
      CONCLUSIONS: The PTB case detection rate in Burkina Faso is low, due to the loss
      of cases at each of the stages leading to the diagnosis of TB. Case detection
      depends on the operational effectiveness of the staff working in the health
      services, as well as the referral of suspect patients to the CDT.

PMID- 16602410
TI  - Benefit of amoxicillin in differentiating between TB suspects whose initial AFB
      sputum smears are negative.
AB  - SETTING: Out-patient dispensary in Conakry, Guinea, West Africa. OBJECTIVE: To
      differentiate between pulmonary tuberculosis (PTB) and non-PTB diseases among 204
      acid-fast bacilli (AFB) smear-negative adult TB suspects. DESIGN: We derived
      scores from clinical, serological and radiological findings among PTB suspects
      aged > or = 15 years who, after having had three AFB-negative smears, were
      treated for 10 days with amoxicillin (AMX, 1.5 g/day). RESULTS: At the selected
      cut-off score from model 1 (clinical), sensitivity for PTB was 95%, specificity
      40%, negative predictive value (NPV) 84%, and positive predictive value (PPV)
      69%. Comparable values from model 2 (clinical + serological + radiological) were:
      sensitivity 99%, specificity 45%, NPV 97%, and PPV 71%. Results from AMX were
      better: sensitivity 92%, specificity 93%, NPV 94%, and PPV 91%. Of the 117
      suspects who failed to respond clinically and radiographically to AMX and
      remained AFB smear-negative, 110 (94%) had PTB, confirmed either by positive
      culture (73 patients) or response to anti-tuberculosis treatment (37 patients).
      CONCLUSION: The clinical and radiographic response to AMX is better than derived
      scores at differentiating between PTB and non-PTB in TB suspects presenting to a
      dispensary in Guinea, a low HIV-seroprevalence country.

PMID- 16602411
TI  - From microscopy centre to culture laboratory: a viable ride for mycobacteria.
AB  - SETTINGS: Culture and drug susceptibility testing of Mycobacterium tuberculosis
      is required for the treatment of drug-resistant tuberculosis. Cetylpyridinium
      chloride-sodium chloride (CPC-NaCl) solution is recommended for the preservation
      of sputum during transport. OBJECTIVE: To study the possibility of sputum
      preservation and transport in CPC-NaCl and its effect on culture. DESIGN: Sputum
      specimens preserved with CPC-NaCl were transported to the laboratory for culture
      from remote microscopy centres of Andhra Pradesh and Orissa states, India.
      RESULTS: Of the 175 specimens, 140 (80%) yielded mycobacteria, 21 (12%) did not
      yield any growth, 11 (6.2%) grew contaminants and 3 (1.7%) were lost due to
      leakage. Culture positivity was greater in specimens stored for 1 week. Culture
      results from specimens stored for 2 weeks are encouraging. CONCLUSION: The CPC
      NaCl preservation technique can be used for effective preservation and transport
      of

PMID- 16602412
TI  - Blood agar for susceptibility testing of Mycobacterium tuberculosis against first
      line drugs.
AB  - OBJECTIVE: To evaluate the performance of blood agar for the susceptibility
      testing of 50 Mycobacterium tuberculosis clinical isolates against isoniazid
      (INH), rifampicin (RMP), streptomycin (SM) and ethambutol (EMB). DESIGN: The
      activity of the drugs was determined by the proportion method on blood agar
      instead of Middlebrook 7H10 agar according to Clinical Laboratory Standard
      Institute recommendations. The final concentrations of INH, RMP, SM and EMB were
      0.2 microg/ml, 1 microg/ ml, 2 microg/ml and 5 microg/ml, respectively. RESULTS:
      The results were compared with the radiometric proportion method as the
      reference, and the agreements were determined as 100% for INH and RMP, 92% for SM
      and 96% for EMB. The specificity, sensitivity, positive predictive value and
      negative predictive value were 90.4% and 97.5%, 100% and 90%, 66.6% and 90% and
      100% and 97.5% for SM and EMB, respectively, while these values were 100% for INH
      and RMP. The results of susceptibility testing were obtained on the 14th day of
      incubation. CONCLUSION: According to this preliminary study, our results suggest
      that blood agar can be used as an alternative medium for the susceptibility
      testing of M. tuberculosis strains against INH, RMP, SM and EMB in resource
      limited countries. However, further studies are needed before implementating the
      method in diagnostic laboratories.

PMID- 16602413
TI  - Evaluation of alternatives to RFLP for the analysis of clustered cases of
      tuberculosis.
AB  - BACKGROUND: Mycobacterial interspersed repetitive unit-variable number tandem
      repeat (MIRU-VNTR) analysis is a recently developed method which could be
      suitable as a 'real-time' genotyping tool for Mycobacterium tuberculosis.
      METHODS: One hundred and thirty-four M. tuberculosis isolates were analysed using
      the reference method, IS6110-restriction fragment length polymorphism (RFLP), and
      by MIRU, alone and together with spoligotyping. RESULTS: MIRU reduced the
      genotyping turnaround time by 21 days. The discriminatory power (HGDI) for MIRU
      and RFLP was 0.978 and 0.989, respectively. RFLP clustered 41.8% of the isolates
      (17 clusters; 2-9 representatives), whereas MIRU increased the number and size of
      the clusters (57.5% of the isolates in 20 clusters; 2-14 representatives). With
      respect to the RFLP clusters, MIRU data showed full correlation in only 7/ 17
      (41%) clusters and low correlation in 8/17 (47%) clusters. When MIRU and
      spoligotyping were considered together, the analysis fitted better with RFLP
      data: 1) 42.5% of the isolates were grouped in 20 clusters of 2-6
      representatives, and 2) the number of clusters with full correlation with RFLP
      data increased to 11/17 and those with low correlation decreased to 2/17.
      CONCLUSION: MIRU-VNTR analysis showed low correlation with RFLP. The addition of
      spoligotyping to MIRU analysis fitted much better with RFLP analysis, although
      full correlation was still not achieved.

PMID- 16602414
TI  - Targets for global tuberculosis control.
AB  - The United Nations Millennium Development Goals (MDGs) have added to the suite of
      targets and indicators used to evaluate progress in tuberculosis (TB) control.
      This paper reviews the history of target setting for TB control and lays out the
      complete set of indicators and targets that will guide TB control through to
      2015, the target year for all MDGs.

PMID- 16602415
TI  - Evaluation of a proposed diagnostic scoring system for pulmonary tuberculosis in
      Brazilian children.
AB  - In a case-control study to evaluate a systematic scoring system for diagnosing
      pulmonary tuberculosis (PTB) in children, cases had gastric lavage cultures
      positive for Mycobacterium tuberculosis and recovered after anti-tuberculosis
      treatment, while controls had negative cultures and recovered with non-anti
      tuberculosis treatment. Radiological aspect (OR = 25.39), contact with a
      tuberculous adult (OR = 10.67) and tuberculin skin test > or = 10 mm (OR = 8.23)
      were associated with PTB diagnosis. The sensitivity of the score ranged from 58%
      to 89% and the specificity from 98% to 86%, with cut-offs of respectively > or =
      40 or > or = 30. The scoring system may be a useful diagnostic method in areas
      with a high prevalence of TB.

PMID- 16602416
TI  - Status of bacillary tuberculosis cases identified in a community survey under
      different control programmes.
AB  - We report the status of bacillary tuberculosis (TB) cases identified in community
      surveys undertaken at 2.5-year intervals. We observed three cohort periods to
      represent the different TB control programmes, namely 12-18 months of treatment
      (pre-short-course chemotherapy [pre-SCC]), 6-8 months SCC and DOTS in the area.
      There was a significant reduction in deaths from 23% to 17%, and an increase in
      the proportion of cases negative by smear and/or culture for Mycobacterium
      tuberculosis, from 54% to 58% in the pre-SCC and SCC cohorts to 80% in the DOTS
      cohort. These findings suggest that the DOTS strategy could have a significant
      influence on TB epidemiology.

PMID- 16602417
TI  - Prevalence of Beijing genotype Mycobacterium tuberculosis strains in Istanbul.
AB  - To determine the prevalence of Beijing genotype Mycobacterium tuberculosis in
      Istanbul, 4069 strains were subjected to DNA fingerprinting. This is the first
      study to reveal the presence of the Beijing genotype in Istanbul. The prevalence
      rate was estimated as 1.13%, and it was shown that these strains were carried
      over from countries of the former Soviet Union. The study also showed that the
      prevalence of the Beijing genotype among at least rifampicin (RMP) resistant
      strains was significantly higher (2.7%) than among RMP-susceptible strains
      (0.9%).

PMID- 16602418
TI  - [Current problems of hygiene and epidemiology].
AB  - In this review, the data available in the literature concerning determinants of
      human health from the public health point of view have been summarized. Presented
      newest concepts of human health include genomic and proteomic perspectives in the
      complex web of interactions between genes and environment. In 2002 epidemiologist
      and hygienist also has an access to an almost complete description of a single
      human genome but the challenges remain to move from the description to
      understanding the function of the genome. Studying the role of molecular
      determinants of human health is an area of research that has gained attention,
      particularly during the past 50 years, since the structure of DNA helix has
      solved. This field will become more dynamic one in the near future and the
      important data will rapidly accumulate. Further researches are clearly needed to
      determine not only carcinogenic potential of human ecosystems, but also to
      establish new methods of risk assessment. The knowledge gained will be crucial in
      prophylactic health care systems.

PMID- 16602419
TI  - [Views of graduates of Medical Faculty, Poznan University of Medical Sciences on
      pharmacy].
AB  - Cooperation among many medical specialties is a necessity. The health care system
      efficiency stems not only from its organisational structure but also from joint
      action of the basic functional units, including the interpersonal collaboration
      of various medical experts. The combined knowledge among pharmacists and
      physicians about their respective medical competencies and professional faculties
      may only enhance such cooperation. The basic argument here is that the knowledge
      on the pharmaceutical profession among physicians is rather modest. To test that
      assertion, medical students of the sixth (the last) academic year, Medical
      Faculty I, the University of Medical Sciences in Poznan, were asked on the issue,
      through a special questionnaire. The conclusions may prove helpful in perfecting
      educational programmes in the field of Public Health.

PMID- 16602420
TI  - [Monitoring and evaluation of effectiveness of the postgraduate training in
      occupational hygiene].
AB  - The large scope and thematic diversity of the postgraduate education, led in
      great part on commercial principles in conditions of the increasing competition
      on educational market, is connected with particular expectations and with the
      growing critisism of the students, and is critically observed by employers,
      professional circles and public opinion. Therefore monitoring and evaluation of
      the postgraduate training quality acquire an importance. Quality is understood
      here as efficiency, i.e. the level of real achievement of educational objectives
      with preserving defined standards of the professional knowledge and skills. In
      the years 1998-2001 in the Nofer Institute of Occupational Medicine in Lodz the
      students assessed with the help of special questionnaires training programs,
      courses' contents and teaching personnel of all postgraduate training cycles in
      occupational hygiene. The evaluation studies with the use of a questionnaire of
      acquired competencies self-assessment was also carried out. The data gathered in
      this way were included in the reports directed to the course managers, and
      afterwards subjected to a comparative analysis in result of which the degree in
      which particular curricula in occupational hygiene produced professional
      competencies' increase perceived by the students was defined, the degree in which
      particular teaching subjects and classes influenced occupational hygiene
      knowledge and skills of the students was pointed out, and the quality of
      professional and didactic skills of the members of teaching personnel was
      defined, as perceived by the students.

PMID- 16602421
TI  - [The place and role of evidence-based medicine and health economics in public
      health].
AB  - The paper aims to sketch both the common and the divergent features of health
      economics and evidence-based medicine. This goal was attained by examining both
      disciplines regarding their definition approaches and subject areas (research
      interests). The discussion centres around the opinion that the development of
      evidence-based medicine contributes to a growth of interest in research topics
      concerned with economic analyses, including the techniques endorsed in evaluation
      studies. The paper supports the argument that health economics and evidence-based
      medicine develop extraordinarily quickly, become more and more noticed and
      increasingly widely applied in clinical practice.

PMID- 16602422
TI  - [The assesment of health status of adolescents exposed to tobacco smoke with
      cotinine as an exposure biomarker].
AB  - The aim of the study was the assessment of the health status of adolescents
      exposed to tobacco smoke. The questionnaire and internal examination covered 202
      of Lodz high school students. The tobacco smoke exposure was assessed by cotinine
      measurement in urine with the HPLC method. The results indicate intensive passive
      and active exposure to tobacco smoke among the examined adolescents, which was
      reflected in the cotinine levels in urine, 30-40 times higher in smokers than in
      the remaining subjects. The active smokers more frequently manifested problems of
      respiratory nad neurovegetative systems, however there were no differences in the
      subjective study results as well as in the frequency rate of using health care
      services by the active smokers and the remaining subjects.

PMID- 16602423
TI  - [Rhythm of life of Poznan Medical University students' and hygienic norms].
AB  - The influence of the lifestyle on one's health has been widely discussed in
      recent years. For individual to enjoy good health, both physical and
      psychological, fairly regular rhythm of life is needed, with sufficient time for
      work (study), rest and sleep. This article discus Medical University students'
      rhythm of life, especially amount of time devoted to study, rest and sleep. These
      results were compared with relevant hygienic norms. Medical students' rhythm
      differ from above norms and doesn't help maintaining good health or improving it.

PMID- 16602424
TI  - [Vitamins and minerals intake in hyperlipidemic outpatients].
AB  - Dietary modification is the first line treatment in cardiovascular disease. The
      dietary recommendations focus on the consumption of total fat, saturated fatty
      acids and cholesterol, additionally the adequate intake of some vitamins and
      minerals is also important. The purpose of this study was to evaluate vitamins
      and minerals intake in hyperlipidemic outpatients. The studied group comprised
      103 women, with BMI 28.4 +/- 6.77 men with BMI 29 +/- 4.8, aged 20-60 years.
      Dietary assessment was based on 3-d food records. The energy intake in women was
      1824.1 +/- 576 kcal/d, in men 2246.6 +/- 679 kcal/d. The average intake above the
      RDA was for vitamin A (147.5 +/- 94% of the RDA in women, 143.2 +/- 138% in men)
      vitamin E (119.8 +/- 58.7%, 130.2 +/- 76%), very close for vitamin B in women
      (98.9 +/- 33.1%) and in men additionally for iron (134.8 +/- 56%), niacin (110 +/
      38%) and vitamin B6 (101.7 +/- 36.2%). The lowest percentage of the RDA was for
      calcium (62.2 +/- 38%, 69.8 +/- 40.7%) and magnesium (76.2 +/- 25%, 78.6 +/-
      24.6%) in women as well as in men and for vitamin B1 in women (76.2 +/- 28%) and
      for vitamin B2 in men (78.4 +/- 36.6%). The percentage of the RDA for vitamin C
      was 85.1 +/- 49% in women and 85.2 +/- 61.8% in men. In this studied group the
      low intake of certain vitamins and minerals was found. The nutritional education
      is required, which is aimed not only at lower intake of fat, saturated fatty
      acids and cholesterol, but also at adequate consumption of vitamins and minerals.

PMID- 16602425
TI  - [Modified smectite rocks from Poland enhance removal of some organic compounds
      from natural surrounding].
AB  - The organic compounds (phenol, aniline, naphthalene, petrol) are the pollutants
      which are most frequently encountered in the natural environment. Even small
      amounts of these compounds may create the hazard to living organisms. The
      absorption methods are used to neutralize these pollutants and to prevent their
      dissemination. The objective of these paper was to evaluate the activity of
      organo-smectite compounds (with respect to phenol, aniline, naphthalene and
      petrol) using the silty minerals as sorbents. The silty minerals are known for
      their absorption capability of some organic compounds-mostly cations and base
      solutions. Only the trace amounts of non ionic compounds (phenol,benzene,dioxins)
      are absorbed by these minerals. Should the long chain ammonic cations with
      various length of hydrocarbon chain be introduced at the exchange site, the
      absorption capability of these compounds and their organophylic properties are
      greatly improved and their surface became organophylic. The bentonites and
      smectite silts (from Chmielnik, Milowice, Mecinka, Adamowa and Dylagowka) were
      used for preparation of sorbents. The laboratory tests had indicated that all
      smectites treated with ammonia salts create the organic-mineral compounds and
      that modification of smectites (increase of cation length) changes properties of
      their surface (hydrophilic character is changed to hydrophobic). The organic
      smectites have a very good sorption properties with respect to the organic
      compounds mentioned before.

PMID- 16602426
TI  - [Prevention and health promotion programmes on websites of the Polish health
      insurance funds].
AB  - OBJECTIVE: The aim of our study was to evaluate the content and presentation of
      prevention and health promotion programmes on websites of the Polish health
      insurance funds. DESIGN: A systematic review of the content of official websites
      of all 17 national health insurance funds was done. RESULTS: Information on
      health care programmes was given on 12 websites, In four cases information can be
      described as sufficient and in only one case the programme was described in
      detail. Health insurance funds in Poland make extensive use of the Internet to
      communicate with contractual service providers. However, there is much to be done
      concerning communication with the patients.

PMID- 16602427
TI  - [Knowledge of healthy behaviours among teenagers attending selected schools of
      the Lublin region].
AB  - It is commonly known that protection of human health depends to greatest extent
      on knowledge and actions good or hazardous for it. Childhood and youth are
      periods of life when education is more likely to have the best results. The aim
      of my paper was evaluation of the level of teenagers' knowledge of prohealth
      behaviours. The survey, in accordance with the standardised interview method, was
      carried out among the group of 100 secondary school students in the Lublin
      region. As a result it was proved that the level of the students' knowledge of
      certain prohealth behaviours varies. Negligence in health education is confirmed
      by a considerable percentage of wrong answers to questions concerning physical
      activity, selected issues from hygiene and stress. Health awareness among
      teenagers is moulded mainly by mass media and peers. The majority of the
      respondents admit incomplete knowledge of the subject. Since the role of the
      family in health education is rather limited, and the school includes this issue
      in its teaching programme to small extent, it would be desirable to place "health
      education" among other school subjects.

PMID- 16602428
TI  - [Problem based learning in public health].
AB  - The article depicts selected methods of problem based learning. Medical students
      were asked for their opinion on the way the quality of education was evaluated.
      Furthermore, the educational objectives in the field of Public Health were
      analysed. The results point to the possibilities of applying these methods in
      teaching of Public Health in the Poznan University of Medical Sciences.

PMID- 16602429
TI  - [Interpersonal relations in the consciousness of pupils and students].
AB  - The quality, satisfaction and being pleased of life depend on proper relations in
      the family, in the group of persons at the same age and at school or at the
      University. The aim of this study was the estimation of interpersonal relations
      in the chosen group of Cracovian secondary school pupils and medical students
      thanks the examinations conducted by auditory system with the use of an inquiry
      "Woman Self Image and Social Ideal". There were 713 persons belonging to 2 groups
      included in the examination: Group I: 313 pupils, including 128 boys and 185
      girls attending to the second and third classes of two Cracovian secondary
      schools: Group II: 400 students of Medical Department and Health Protection
      Department of Collegium Medicum, Jagiellonian University in Cracow--106 male
      students and 294 female students. In the actual analysis the answers given to 64
      questions of the "Interpersonal problems Inventory" questionnaire were estimated.
      Every question contained 5 possibilities: no, a little bit, more or less, much,
      very much. The hierarchy of these problems was estimated with the use of the
      method of step wise regression on the basis of the frequency of opposite answers
      to the particular questions. The most often the young persons stated (74%-63%)
      that it is never difficult for them to make a present to somebody else, to feel
      happy about one's happiness and to show positive emotions to others. About half
      of the examined persons (60%-47%) thought that they were never aggressive to
      others, that they never put their needs on the first position and they were not
      afraid of contacts with other people. In the questions connected with one's own
      personality determining the frequency of answers given to particular dystractors
      was not strongly marked e.g.: It is difficult for me to be alone: no
      (39%I/35%II), a little bit (18%I/16%II), moderately (13%I/11%II), much
      (13%I/18%II), very much (17%I/20%II); I am too credulous: no (46%I/37%II), a
      little bit (26%I/ 26%II), moderately (12%I/18%II), much (9%I, 12%II), very much
      (7%I, 7%II). The frequency of opposite answers with negative meaning as a rule
      did not exceed 5%.

PMID- 16602430
TI  - [The image of oneself--in the opinion of Cracovian pupils and students].
AB  - A proper and of many directions development of young person's personality
      requires the acceptance of oneself with the skill of individual identity building
      and being autonomic person. With the end with safety time in childhood young man
      has to make a confrontation of formed by over-protective parents image of oneself
      with perception of him/herself by persons at the same age or by adults. This
      confrontation may often appear to be disadvantageous. It may lead to the
      development of acquired emotional deficiency syndrome. Young person loses self
      confidence, cannot lose, does not undertake any risk or actions requiring
      obstinacy and endurance. The examination embraced 857 persons (457 pupils of
      second and third classes of Cracovian secondary schools and 400 students of
      Collegium Medicum, Jagiellonian University, Cracow. On the basis of selected
      questions from "Eating Disorders Inventory" questionnaire being a part of "Woman
      Self Image and Social Ideal" inquiry it was stated that: 1. About 1/3 of examined
      persons wanted to avoid their parents being disappointed but the safety of
      childhood time was desired (always or usually) by 10% of pupils and 8% of
      students--more often women than men. Half of the examined persons both pupils and
      students rarely or never show such desires. 2. 13% of examined persons think that
      the requires of adult life are far too big--more often in the group of men that
      in the group of women. 3. Approximately 8% of examined persons want to be
      somebody else. 56% of examined women and 83% of examined men want to be who they
      are. 4. High level of expectations towards oneself show more or less 26% of
      pupils and students, a little bit less give contrary answer. The examinations did
      not show important differences in the aspect of analyzed problems between
      students and schoolchildren.

PMID- 16602431
TI  - [Epidemiology of selected infectious diseases in Wielkopolska district in the
      years 1988-2000].
AB  - Infectious diseases are an ever important medical problem. Health Service
      reorganization, may contribute to further increase of the diseases. The aim of
      the study was the retrospective analysis of the incidence of selected infectious
      diseases in Wielkopolska and the comparison of the regional and national data.
      Incidence of infectious diseases in Wielkopolska in the scrutinized period was
      lower than the national one, except 1990 & 1992. The value of incidence for
      tuberculosis for Wielkopolska various from the national trend which decreases
      noticeably and significantly from 1997. No other permanent trends in the
      incidence of infectious diseases were observed throughout the analyzed period.

PMID- 16602432
TI  - [Example of anthropological epidemiology--an evaluation of trend of changes in
      blood pressure values in children and adolescents].
AB  - Traditional direction of epidemiology, focused mainly on studying most frequently
      occurring diseases, is a subject for continuous changes. Complexity of the health
      evaluation problems brings about the development of new branches of this science.
      In pediatrics evaluation of the health status is most frequently based on
      positive and negative health measurements. The aim of this study was the
      evaluation of trend of changes in blood pressure values in connection with
      certain morphological features (height & weight). The population studied were
      children and adolescents age 10-18 from Poznan's cross-sectional blood pressure
      studies performed in 1986 & 1996. In these studies decrease of blood pressure
      values and simultaneous deceleration of anthropological features were observed.
      Presented direction of change of morphological and physiological features shows
      the need for updating developmental norms in children and adolescents.

PMID- 16602433
TI  - [Causes of hospital admission among 40-year-olds].
AB  - The work constitutes a part of the larger project "Comparative analysis of some
      elements of health state among 40-year-old inhabitants of the City and the
      Province of Poznan, born 1938, 1959", backed by National Committee of Sciences,
      performed in the Dept. of Public Health, Chair of Social Medicine, K.
      Marcinkowski University of Medical Sciences, in Poznan. Altogether 1037 persons,
      born in 1959, were medically examined as to their social background, education,
      life-style, and their current health picture. Some of the key elements were
      compared, where possible, with a similar, though much larger group of those born
      in 1938. The article focuses on the 40-year-olds born in 1959, and describes the
      causes of their hospitalisation throughout the year preceding the examination.
      Place of residence, gender and education of the persons examined were taken into
      consideration. The results point to the prevailing causes of hospitalisation,
      such as cardiovascular disease, diseases of the digestive and urinary tract, and
      consequences of accidents and poisonings.

PMID- 16602434
TI  - [The epidemiological situation regarding cardiovascular diseases in the Lodz
      voivodship as a justification for prevention programmes].
AB  - The analysis of the epidemiological situation regarding cardiovascular diseases
      in the Lodz region arouses justified anxiety. The relevant data were obtained
      from the Regional Centre of Public Health in Lodz and from the Central
      Statistical Office. The cardiological prevention programme implemented in the
      Lodz Regional Sickness Fund has both intervention and education features. Its aim
      is to identify the risk factors for cardiovascular diseases and to trigger
      activities related to health education. In 2001, the programme was carried out on
      three levels: in basic health-care units, in cardiological dispensaries, and in
      highly-specialised clinical establishments. 13,790 medical consultations were
      financed by the programme, which cost 369 751 zlotys.

PMID- 16602437
TI  - [An alternative approach to the teaching of obesity as a civilization-related
      disease].
AB  - Universities are relying on student-activating methods in teaching. This work was
      concerned with an approach to teaching of obesity as a civilization-related
      disease to medical students. Brainstorming, snowball discussion, careful reading
      of medical texts, evidence-based medicine, and practicals on how to measure BMI
      and WHR were exploited. Analysis of medical histories to disclose risk factors of
      ischemic heart disease and polymetabolic syndrome X are proposed. Pharmacological
      and non-pharmacological therapies of obesity and its disorders are presented.

PMID- 16602435
TI  - [Contribution of family doctors to health promotion among their patients].
AB  - Health promotion is a major task of family doctors. Doctors contribute to health
      promotion by e.g. providing information to their patients on health promoting as
      well as harmful behaviours. The aim of the study is to find out how frequently
      family doctors undertake health promoting actions among their patients and to
      determine a likely difference in these actions between public and non-public
      health care institutions. The investigations were carried out among patients of
      two basic health care institutions, public and non-public, in Bialystok. Of all
      patients aged 18 and over being under care of family doctors, 1000 people were
      drawn (500 from each institution). Mail questionnaire technique was employed. Of
      579 returned questionnaires, 560 were used for analysis. The analysis included
      situations the patients encountered at the family doctor's. Responding to the
      question whether during a visit the family doctor referred to tobacco smoking,
      mode of nutrition, physical activity, harmful effects of alcohol abuse and the
      way of coping with stress, the patients declared that a given situation occurred
      "always", "frequently", seldom" and "never". Family doctors most frequently
      discussed the problem of nutrition and physical activity, while alcohol drinking
      and tobacco smoking were most seldom touched upon. No significant difference was
      found in the frequency of health promoting actions between family doctors in
      public and non-public institutions of health care.

PMID- 16602436
TI  - [Prevalence of refractive errors in 7 and 8 year-old children in the province of
      Western Pomerania].
AB  - PURPOSE: To determine the prevalence of refractive errors in 7 and 8 year-old
      schoolchildren in the province of Western Pomerania. MATERIAL AND METHODS: 140
      pupils of elementary schools were examined. Measurements of visual acuity and
      retinoscopy after cycloplegia were carried out. RESULTS: Prevalence of hyperopia,
      myopia, and astigmatism was 76.1%, 3.3% and 5.1%, respectively. No statistically
      significant differences between 7 and 8 year-old children were found.
      CONCLUSIONS: 1. There is a relatively high prevalence of refractive errors, with
      hyperopia prevailing, among 7 and 8 year-old schoolchildren. 2. Myopia in young
      children is a cause for concern an further studies. 3. High prevalence of
      refractive errors in children calls for systematic examination and focused
      interviewing by medical professionals of the school health care system.

PMID- 16602438
TI  - [Antioxidant vitamins status in patients with combined hyperlipidemia].
AB  - Diet can influence on the balance between antioxidants and prooxidants in the
      organism. The activity of enzymatic components of antioxidant system can be
      changed, the amount of harmful substances can be increased. The purpose of this
      study was to assess the effect of diet on vitamin A, E, C serum concentration in
      patients with combined hyperlipidemia. The studied group consisted of 38
      subjects, aged 20-60 years. Dietary assessment was based on 24-h dietary recall.
      Serum lipids concentrations were assessed by enzymatic methods, serum vitamins
      concentrations were assessed by HPLC method. The energy intake in men was 2269.6
      kcal, vitamin A consumption was 888.3 microg, vitamin E 8.7 mg and vitamin C 68.6
      mg. In women energy intake was 2112 kcal, consumption of vitamin A was 580
      mcirog, vitamin E 7.8 mg and vitamin C 68.6 mg. Only in 1 men deficient
      concentration of vitamin C was stated. Deficient concentration of vitamin A was
      not found but the desirable concentration was stated only in 5 men. The desirable
      vitamin E level was found only in men, not in women. The correlation between
      vitamin intake and its serum level was not observed. However, in women the
      correlations between intake of protein, dietary fiber, percentage of energy
      derived from fat and vitamin A serum level were found. To conclude, the serum
      concentration of antioxidant vitamins is determined by diet composition, adequate
      in energy and nutrients content.

PMID- 16602439
TI  - [Effect of electromagnetic field produced by mobile phones on the activity of
      superoxide dismutase (SOD-1)--in vitro researches].
AB  - The aim of the paper was to estimate in vitro the effect of electromagnetic field
      produced by mobile phones on the activity of superoxide dismutase (SOD-1) in
      human blood platelets. Suspension of blood platelets exposed to the
      electromagnetic field of 900 MHz frequency for 1, 3, 5, 7 minutes. Our studies
      demonstrated that microwaves produced by mobiles significally depleted the
      activity of SOD-1 after 1, 5, 7 min. of exposition and increased after 3 min. nn
      comparison wit control test. On the ground of our results we conclude that
      oxidative stress after exposition to microwaves can be the reason of many
      disadvantageous changes in cells and may cause many systemic consequences in
      human organism.

PMID- 16602440
TI  - [Copper content in rheumatoid arthritis patients].
AB  - The aim of the study was to test the content serum, erythrocytes and hair copper
      and the relation between the level of copper and the activity disease in the
      rheumatoid arthritis (RA) patients. The subjects of this research were 58 persons
      with RA. In the control group there were 27 healthy subjects. The concentration
      of copper were determined by atomic absorption spectroscopy. The obtained results
      showed significant increase of the mean concentration of serum copper in RA
      patients (19.1 +/- 4.5 micromol/L) in comparison with control group (14.2 +/- 2.7
      micromol/L, p < 0.001). The mean level of hair copper was also significantly
      increased in the examined group (14.3 +/- 4.2 microg/g dry mass) in comparison
      with healthy subjects (10.4 +/- 3.7 microg/g dry mass, p < 0.01) and considerably
      lower in erythrocytes (RA patients - 67.6 +/- 13.4 microg/dL, control group--84.2
      +/- 8.2 microg/dL, p < 0.001). Moreover, it was established that mean serum
      copper concentration in the examined group was significantly correlated with
      erythrocyte sedimentation rate (r = 0.48, p < 0.001) and Ritchie articular index
      (r = 0.36, p < 0.01) and negatively with hemoglobin (r = -0.41, p < 0.01). Copper
      content is not dependent on sex, age and disease duration.

PMID- 16602441
TI  - [Allergens of home environment].
AB  - Exposure for various bio-chemical factors, which are regarded as potent allergens
      is growing rapidly in human population. The reasons are mainly connected with
      working environment and hazzards at workplace, and, on the other hand, with home
      environment. What's more important, there is a rapidly growing incidence of
      allergic reactions to many biological (i.e. ascares, fungi, cockroaches etc.)
      factors, associated directly with our place of living. Additionally
      hypersensitivity can be released or enhanced by various other environmental
      factors, especially by air pollution. The aim of this study was to summarize the
      most frequent potential allergens, which started to appear in our homes.

PMID- 16602442
TI  - [The appreciation of the medical students' knowledge concerning the role and work
      of medical care funds in Polish health care system].
AB  - The aim of the research was verification and comparison of the present state of
      knowledge among the students (of different departments and years ofstudy), about
      the role ofMedical Care Funds in the up-to-now healthcare system and the
      patient's rights as far as the students' future profession as doctors, dentists
      healthcare managers and medical rescuers is concerned. The research was carried
      out by means of anonymous questionnaire. A uniform "assessment" method was
      adopted following the principles of didactic measurement. The following were
      calculated: range, modal, mediana, arithmetic average, variance, standard
      deviation, easiness of the task, difficulty of the task, skip fraction, the
      task's differentiating power, reliability coefficient of the test using the own
      modification of the Excel programme. No significant differences among the
      particular groups have been proven as far as the students present state of
      knowledge is concerned. The research showed different difficulty levels of the
      particular questions among examined groups. The assessment of the up-to-now work
      of the Medical Care Funds is negative in the opinion of the respondents, no
      matter which medical faculty they have represented.

PMID- 16602443
TI  - [Accidents and injuries among children and teenagers documented by the ambulance
      service in Poznan].
AB  - Call records of the Ambulance Service in Poznan have been reviewed to disclose
      the type of accidents suffered by children and teenagers, causes and
      circumstances, and to define some preventive measures. it was found that there
      were 1347 injuries in 2001. Boys were more often involved (60%) than girls (40%).
      The number of accidents increases with age, with a peak at 17-18 years of age.
      Head injuries prevail, accounting for 39.4% of all cases. Injuries are due to
      falls (28), traffic accidents (16%), and pedestrian accidents (14%). Most of the
      injuries happen at home and in its vicinity (38%)

PMID- 16602444
TI  - The World Health Assembly held its fifty-eighth session from 16 to 25 May this
      year.

PMID- 16602445
TI  - Coronary heart disease risk-factor profile in a lower middles class urban
      community in Pakistan.
AB  - We determined the risk-factor profile and prevalence of coronary heart disease in
      Metroville, a lower middle class urban community in Karachi, and compared them to
      the Pakistan health survey PNHS 1990-94, and the US health and nutrition survey
      1988-94 NHANES111. Subjects < 18 years and pregnant women were excluded as were
      people with extreme ranges BMI [corrected] heart rate, height and waist. The
      prevalence of hypertension was 23% in men and women, hypercholesterolaemia was
      17% in men and 22% in women (P < 0.001). Hyperglycaemia was present in 5% of men
      and women and obesity in 33% of men and 47% of women (P < 0.001). Compared to
      PNHS, the prevalences of obesity, hypertension, hypercholesterolaemia and WHR
      were higher in our population. Mean values of BMI [corrected] cholesterol, WHR
      were higher in the US population while mean values were lower for diastolic blood
      pressure and blood glucose.

PMID- 16602446
TI  - [Cancer of the jaw and oral cavity in the Syrian Arab Republic: an
      epidemiological study].
AB  - Oral cancer ranks sixth globally among cancers in terms of prevalence. It is a
      challenge to physicians, a serious problem to patients and a human and financial
      loss to the community. This study was conducted to identify the epidemiological
      factors relating to oral cancer in the Syrian Arab Republic in line with the
      International Dental Federation recommendations which emphasize the need to focus
      efforts on oral cancer. The study, conducted between 1996 and 2001, involved
      outpatients with oral and jaw cancer at several government hospitals. Data were
      collected from the hospital archives, recorded on special forms and analysed.
      Recommendations are presented.

PMID- 16602447
TI  - Tobacco cessation in a population over age 15 years: a community-based survey in
      Alexandria.
AB  - A survey of 2120 adults in Alexandria, Egypt, studied the determinants and
      patterns of tobacco cessation among ever smokers. Ever smokers were 30.7% of
      respondents; only 3.5% had given up smoking (quit ratio of 11.4%). The quit ratio
      was significantly lower for ex-daily smokers (7.5%) than for ex-occasional
      smokers (44.8%). Among current smokers, 56.3% were between the contemplation and
      preparatory phases for quitting, whereas 25.1% were in the action phase of
      attempting to quit, for an average duration of 2.5 months, before relapsing.
      Health concerns were the motive for all ex-smokers and 95.0% of attempters, but
      craving for nicotine was the commonest reason for relapse. Tobacco cessation was
      predicted by older age of tobacco initiation, shorter duration of use, presence
      of health problems and a perception of the benefits of quitting.

PMID- 16602448
TI  - Incidence of haemoglobinopathies detected through neonatal screening in the
      United Arab Emirates.
AB  - In January 2002, a pilot programme of neonatal screening for sickle cell disease
      was launched in the United Arab Emirates (UAE) in 3 districts of Abu Dhabi
      emirate. This paper reports the incidence of sickle cell diseases, other
      haemoglobinopathies and haemoglobinopathy carriers over a 12-month period using
      high performance liquid chromatography as a primary screening method. The overall
      incidence of sickle cell disease among 22 200 screened neonates was 0.04% (0.07%
      for UAE citizens and 0.02% for non-UAE citizens). The incidence of sickle cell
      trait was 1.1% overall (1.5% for UAE citizens and 0.8% for non-UAE citizens).
      Universal neonatal screening for sickle cell haemoglobin at the national level
      should be considered.

PMID- 16602449
TI  - Evaluation of the national health policy of thalassaemia screening in the Islamic
      Republic of Iran.
AB  - We reviewed the medical and economic burden of thalassaemia major with emphasis
      on prenatal diagnosis for disease prevention as the most economic health care
      policy approach. The current programme in the Islamic Republic of Iran screens
      couples just before marriage, identifies carriers and refers them for genetic
      counselling. We searched the current literature for a refined model and enquired
      into compliance issues in interviews with physicians, couples and families with
      affected children. The programme was unsatisfactory in comparison with comparable
      programmes in the Mediterranean region. We devised a simple decision tree that
      incorporates cost-effectiveness and technical, methodological and social issues
      that affect compliance. While revisions to the policy could improve efficiency,
      follow-up is needed, especially to provide prenatal diagnosis for carrier
      couples.

PMID- 16602450
TI  - Mental health publications from the Arab world cited in PubMed, 1987-2002.
AB  - The study aimed to identify mental health publications in Arab countries cited in
      PubMed from 1987 to 2002 and to analyse the year of publication, journal and
      field of research, specifically for child and adolescent mental health studies. A
      PubMedsearch was performed for all mental health publications followed by an
      analysis of child and adolescent mental health citations. The total number of
      mental health research citations published in Arab countries over the last 15
      years was 338, 1.2% of the total number of citations for biomedical research; 17%
      were on child and adolescent mental health. The most dynamic fields of mental
      health research are anxiety and mood disorders and substance abuse. Child
      psychiatry, especially attention deficit hyperactivity disorder and child autism,
      are not gaining much interest from Arab researchers.

PMID- 16602451
TI  - Subclinical hypothyroidism in lithium-treated psychiatric patients in Tehran,
      Islamic Republic of Iran.
AB  - We investigated thyroid function in 46 (20 female & 26 male) psychiatric
      outpatients on lithium treatment by assessing triiodothyronine, thyroxine and
      thyroid stimulating hormone (TSH) levels. The presence of thyroid antibodies
      (anti-thyroid peroxidase and anti-thyroglobulin) was also assessed. Out of the 46
      patients, 8 (17%) displayed overt hypothyroidism. Of the remaining patients,
      subclinical hypothyroidism was found in 16 patients (35%) and euthyroidism in 22
      (48%). Thyroid antibodies were present in 6 patients in the euthyroid group and 5
      patients in the hypothyroid group. The Pearsor product-moment correlation results
      indicated positive association between TSH level and duration of lithium use and
      age of the patients with subclinical hypothyroidism. Duration of lithium use and
      age could be a reasonable indicator for screening asymptomatic patients for
      subclinical hypothyroidism after starting lithium treatment.

PMID- 16602452
TI  - Comprehensive health assessment of senior citizens in Al-Karak governorate,
      Jordan.
AB  - The health status, mental well-being and functional capacity of senior citizens
      was assessed in a community-based survey of people > or = 60 years in 2004.
      Analysis was performed using logistic and linear regression analyses. Of the 300
      subjects enrolled (53.3% women), 74.4% were affected by chronic diseases, 24.3%
      were classified as depressed and 44.0% had a negative health perception.
      Dependence in instrumental activities of daily living (92.0%) was more frequent
      than dependence in basic activities (28.0%). Women were more likely to be
      depressed, and suffer memory impairment and limitation of functional capacity.
      Increase in depressive symptoms was independently predicted by increased age,
      living alone, poor functional capacity, memory impairment and negative perception
      of health. Low summary performance in instrumental and basic activities was
      independently predicted by increased age, lack of education, high number of
      reported symptoms, depression and memory impairment. Depression, poor functional
      capacity and memory impairment reinforced each other resulting in a state of
      dependency.

PMID- 16602453
TI  - Validity and reliability of the Persian translation of the SF-36 version 2
      questionnaire.
AB  - To assess the validity and reliability of a Persian translation of the SF-36
      questionnaire (version 2) as a tool for use in the general population and
      outpatients, we carried out a cross-sectional study of the staff of Shiraz
      Medical School during November 2001. Response rate was 83.6%. Internal
      consistency for 8 scales using Cronbach's alpha was 0.87 (minimum recommended
      0.85). Construct validity was acceptable as correlation between scales and some
      sociodemographic characteristics was significant. The correlation coefficient
      between 8 scales and related principal components was also acceptable. This
      translation is an appropriate tool for assessing health perceptions of the
      population.

PMID- 16602454
TI  - Screening for microalbuminuria by use of microproteinuria.
AB  - We aimed to develop a reliable, low cost method to assess the early stages of
      renal impairment in diabetes, for use in high-risk populations in countries with
      limited resources. We evaluated a trichloroacetic acid (TCA) turbidimetric method
      for microproteinuria screening in patients with diabetes. The method was compared
      with an immunoturbidimetric procedure for the detection of microalbumuniuria.
      Both methods performed within limits of allowable uncertainty based on inter- and
      intra-individual variation. A urinary albumin/creatinine ratio of 3.0 g/mol,
      assumed as diagnostic of microalbuminuria, was found to correlate with a cut-off
      value of 24 mg/L for microproteinuria. The clinical sensitivity and specificity
      of the TCA method determined against this ratio were 86% and 90% respectively.
      The reliability and practicability of the TCA method renders it suitable for the
      detection of early stage renal damage, with emphasis on screening high-risk
      populations in countries with limited resources.

PMID- 16602455
TI  - Identification of Candida dubliniensis in a diagnostic microbiology laboratory.
AB  - Candida dubliniensis is an emerging yeast pathogen isolated mainly from
      immunocompromised patients. As molecular tests are currently unsuitable for use
      in routine diagnostic laboratories, we compared a variety of phenotypic
      techniques for differentiating C. albicans and C. dubliniensis. The tests
      included: colony colour on CHROMagar Candida medium; growth at 37 degrees C and
      45 degrees C; ability to produce germ tubes and chlamydospores; and the Auxacolor
      system. The organisms included 105 isolates previously identified as C. albicans,
      10 reference strains of C. albicans, 2 reference strains of C. dubliniensis and
      102 fresh clinical isolates identified as C. albicans. None of the tests alone
      was satisfactory but a combination of 3 tests may be suitable for presumptive
      identification of C. dubliniensis.

PMID- 16602456
TI  - Seroprevalence of hepatitis C and risk factors in haemodialysis patients in
      Guilan, Islamic Republic of Iran.
AB  - We assessed the prevalence of hepatitis C virus (HCV) infection and associated
      risk factors for all 298 haemodialysis patients in 7 dialysis units in Guilan
      province. Serum samples were screened for anti-HCV antibodies using a second
      generation enzyme-linked immunosorbent assay. Positive samples were confirmed by
      immunoblot assay. Overall prevalence was 24.8% (range: 9%-40%; 95% CI: 19.9
      29.7): 80 patie.nts tested positive and 74 were confirmed positive by immunoblot
      assay. Length of time on dialysis and history of rejected kidney transplant were
      statistically significantly associated with HCV infection. Age, sex and previous
      blood transfusion were not associated. Nosocomial transmission may play a role in
      the spread of HCV in haemodialysis units. A separate dialysis system should be
      used for seropositive HCV patients.

PMID- 16602457
TI  - Prevalence of intestinal parasitic infections in the Islamic Republic of Iran.
AB  - A national survey of the prevalence of intestinal parasitic infections in the
      Islamic Republic of Iran was made on a random sample of families covered by local
      health centres affiliated to the medical universities. Out of 53,995 people aged
      2+ years, from 12,495 families (0.1% of all families in 1999), 45,128 stool
      samples were analysed by formalin-ether precipitation. Intestinal parasitic
      infections were found in 19.3% of the study population (19.7% male, 19.1%
      female). Giardia lamblia (10.9%), Ascaris lumbricoides (1.5%), Entamoeba
      histolytica (1.0%) and Enterobius vermicularis (0.5%) were the most common
      infections. The infection rate was highest in the 2-14 years age group (25.5%)
      and in rural residents (23.7%).

PMID- 16602458
TI  - Is Q fever an emerging infection in Turkey?
AB  - Between 4 May and 8 August 2002,46 cases of acute fever were reported near the
      Black Sea region in northern Turkey. The infection was treated rapidly and
      successfully with tetracyclines, so clinical diagnosis of rickettsial or
      ehrlichial infection was considered. Analysis of serum and blood samples taken
      from 19 patients identified the causative organism as Coxiella burnetii; 7 cases
      were reported as acute Q fever and 8 as seropositive for past infection. The most
      common clinical symptoms among the acute cases were vomiting (100.0%), nausea
      (85.7%), diarrhoea (57.1%), fever (42.9%), abdominal pain (42.9%) and headache
      (42.9%). Liver enzymes were elevated in all patients. It is considered that
      epidemiological investigation for Q fever will be essential in the affected
      region in future.

PMID- 16602459
TI  - School non-enrollment and its relation with health and schistosomiasis knowledge,
      attitudes and practices in rural Egypt.
AB  - Children who are not enrolled in school are deprived of schistosomiasis
      treatments delivered through school health programmes. We explored perceptions of
      barriers to school enrolment and health and schistosomiasis knowledge, attitude
      and practices among 58 enrolled and 41 non-enrolled children and 80 adults in a
      village in El-Fayoum governate, Egypt. Economic factors, cultural factors and the
      school system were perceived as barriers. Maternal education had a significant
      role in enrolment. Non-enrolled children were more anaemic and had more signs of
      vitamin deficiency. Enrolled children had better schistosomiasis knowledge and
      attitudes, but not practice; both groups had high Schistosoma mansoni infection
      rates (51.7% enrolled and 65.8% non-enrolled). Education and health policies
      should tackle perceived barriers. Introduction

PMID- 16602460
TI  - Active trachoma, face washing (F) and environmental improvement (E) in a high
      risk population in Oman.
AB  - Oman aims to eliminate blinding trachoma by 2010. As a part of a study to review
      the health institution approach of trachoma surveillance, "F" (facial
      cleanliness) and "E" (environmental improvement) components of the SAFE trachoma
      control strategy were assessed in a high-risk population in Nizwa wilayat. Thus
      50 households with 1 member treated for active trachoma in the last 6 months were
      evaluated for active trachoma and forwater and sanitation facilities. In all, 229
      children under 15 years of age were clinically examined; the rate of active
      trachoma was 3.5% in the children. Clean face was found in 97.8% of the children
      and 70% of houses had piped water or water supplied by tankers. The status of "F"
      and "E" in the study area was generally high.

PMID- 16602461
TI  - Risk factors for bacterial vaginosis in women attending a hospital in Kerman,
      Islamic Republic of Iran.
AB  - Bacterial vaginosis (BV) is the most prevalent form of vaginal disturbances in
      women of child-bearing age. This study examined the prevalence and risk factors
      of BV of 130 non-pregnant women attending a hospital of Kerman University of
      Medical Sciences. Prevalence was 37.7%. Patients with BV had significantly lower
      educational and socioeconomic levels. They were also more likely to be smokers.
      The prevalence of BV was higher in patients with a history of abortion but this
      was not statistically significant. Women using oral contraceptive pills were at a
      decreased risk of BV; this was statistically significant. There were significant
      positive associations between BV and a history of vaginal infection, preterm
      delivery and premature rupture of the membranes. As BV appears quite prevalent in
      our patients, and considering the various complications associated with it,
      screening and treatment of high-risk women is suggested.

PMID- 16602462
TI  - [Female drug abuse in a university setting].
AB  - Morocco is a country with Muslim-Arab tradition. In this sociocultural context,
      drug abuse in women is very taboo. We tried to approach the subject of drug use
      in women in a cross-sectional study of a sample of 1208 students (744 women and
      464 men) who completed an anonymous self-administered questionnaire. We found
      6.59% of women and 36.2% of men used drugs. Using DSM IV criteria, drug
      dependence was found in 2% of the subsample of female drug users and drug abuse
      in 1.5%. Place of residence and level of income were statistically significant
      risk factors for drug use.

PMID- 16602463
TI  - Chlorine residual efficiency in inactivating bacteria from secondary
      contamination in Isfahan, 2002.
AB  - To investigate the inactivation of potential pathogens, we evaluated survival
      rates for Escherichia coli, Enterococcus faecalis, Aeromonas hydrophila and
      Salmonella typhi in samples taken from the Isfahan drinking water system.
      Chlorine residual, pH, temperature and total organic carbon levels were measured.
      The organism most sensitive to chlorine was A. hydrophila. It was inactived in <
      100 minutes at chlorine levels of 0.11 mg/L to 0.90 mg/L. The other 3 organisms
      showed higher resistance. E. coli tolerated 0.30 mg/L chlorine for > 1000 minutes
      while Ent. faecalis and S. typhi survived at total chlorine concentration of 0.50
      mg/L for 100 minutes. We concluded that total chlorine levels of less than 0.71
      mg/L in water supply systems cannot provide the recommended safety levels.

PMID- 16602464
TI  - [Analysis of the appropriateness of hospitalizations in Monastir, Tunisia].
AB  - We aimed to measure the extent of inappropriate hospital admissions and to
      identify factors associated with inappropriate hospital use. A descriptive study
      was carried out on a randomized sample of 411 hospitalizations in 3 regional
      hospitals. The appropriateness of admissions was assessed using the
      Appropriateness Evaluation Protocol (AEP). We found 21% (95% CI: 17%-25%) of the
      admissions were avoidable according to the AEP. Inappropriate admissions were
      associated with the hospital (P = 0.005), patient age (P = 0.003), length of stay
      and diagnosis (P < 0.001). The most frequent reasons for appropriate admissions
      were parenteral therapy, an acute or progressive sensory motor circulatory or
      respiratory condition sufficient to incapacitate the patient and severe
      electrolyte or blood gas abnormality. Our study highlights the need to improve
      hospital management and to develop alternatives to hospitalization.

PMID- 16602465
TI  - In vivo antiplatelet effect of intravenous alum in rabbits.
AB  - Traditionally known as a haemostatic agent, alum shows a paradoxical effect of
      increased prothrombin and partial thromboplastin times. This study investigated
      the in vivo effect of alum on platelet aggregation and bleeding time in rabbits.
      The collagen-induced platelet aggregation of platelet-rich plasma samples from 14
      healthy rabbits was measured turbidometrically using a platelet aggregometer,
      before and 1 hour after intravenous injection of alum. Collagen-induced platelet
      aggregation was significantly reduced after alum injection. Bleeding time from an
      ear puncture in 8 rabbits was also significantly prolonged after intravenous alum
      injection. These results suggest that the use of alum as an oral antiplatelet
      drug could be explored further, taking into account possible side-effects
      especially in renal compromised patients.

PMID- 16602466
TI  - Primary care psychiatry: pertinent Arabian perspectives.
AB  - There is substantive evidence of significant psychiatric morbidity among primary
      care patients, mainly in the form of anxiety and depressive disorders. A careful
      critical approach is essential for ensuring the cultural relevance, validity and
      reliability of the psychiatric screening instruments used to identify such
      morbidity. Most psychiatric morbidity among primary care patients passes
      undetected by the primary care practitioners. This will inevitably lead to
      unnecessary investigation and medication and the continuation of suffering for
      patients. Comorbidity and physical presentation in most instances contribute
      significantly to failure to detect psychiatric disorders. To deal with this
      problem of hidden psychiatric morbidity, carefully designed educational and
      training programmes need to be tailored to address the particular weaknesses and
      needs of primary care doctors.

PMID- 16602467
TI  - History of disorders of thyroid dysfunction.
AB  - The first description of thyroid diseases as they are known today was that of
      Graves disease by Caleb Parry in 1786, but the pathogenesis of thyroid disease
      was not discovered until 1882-86. Thyroidectomy for hyperthyroidism was first
      performed in 1880, and antithyroid drugs and radioiodine therapy were developed
      in the early 1940s. Thomas Curling first described hyopothyroidism (myxoedema) in
      1850 and the cause and suitable treatment were established after 1883. This paper
      reviews the main landmarks in the history of thyroid disease, supplemented by a
      brief discussion of the historically relevant scientific aspects of the thyroid
      gland, and the evolution of endocrinology as a formal discipline.

PMID- 16602468
TI  - [Epidemiological and clinical aspects of neurosyphilis in Morocco].
AB  - Neurosyphilis accounts for 56%-70% of all visceral syphilis and is a complication
      in 5%-10% of cases of untreated syphilis. The aim of this study was to evaluate
      the epidemiological aspects and clinical presentations of neurosyphilis in
      Morocco through a series of 201 patients attending the Centre for Neurological
      Services at the university hospital in Rabat between 1986 and 1997. The mean age
      of the patients was 41.26 (SD 9.23) years (range: 17-70 years); the majority
      (91%) were male. The incidence of neurosyphilis in Morocco is high. From 31 cases
      per year in 1985, it has fallen since 1990 to reach 10 cases in 1997. Among the
      different clinical presentations recorded, chronic meningoencepahalitis was the
      commonest, followed by meningovasculitis, tabes dorsalis and optic atrophy.

PMID- 16602469
TI  - Nosocomial blood stream infections in Imam Khomeini Hospital, Urmia, Islamic
      Republic of Iran, 1999-2001.
AB  - In a 2-year retrospective study, the database of the microbiology laboratory of
      the Imam Khomeini Hospital was reviewed to identify patients who had nosocomial
      bacteraemia between 1 May 1999 and 31 May 2001 and identify the pathogen
      responsible and its resisitance to antibiotics. Of 6492 patients in various
      wards, 593 (9.1%) had positive blood cultures; 85 of those (14.3%) had signs of
      potential skin contamination. Gram-positive cocci, including coagulase-negative
      staphylococci, Staphylococcus aureus, Streptococcus pneumoniae and other Gram
      positive cocci, accounted for 42.3% of isolates. Gram-negative bacilli were
      responsible for another 42.3% of isolates; Pseudomonas aeruginosa was the
      predominant isolate. Patterns of drug resistance varied according to species of
      bacteria but were generally quite high.

PMID- 16602470
TI  - Risk factors for severe hypoglycaemia in type 2 diabetic patients admitted to
      hospital in Piraeus, Greece.
AB  - A 3-year study assessed the prevalence and causes of severe treatment-related
      hypoglycaemia in type 2 diabetes mellitus patients admitted to hospital in
      Piraeus. Out of the 2858 patients admitted, 207 (7.2%) had severe hypoglycaemia:
      72 were being managed with insulin, 132 oral hypoglycaemic drugs and 3 combined
      insulin/oral drugs. Only 28.5% of patients were attending a diabetes clinic. The
      cause of the hypoglycaemic attack could be determined for 86.1% of cases; 30.8%
      were due to a missed meal. Interviews showed that education and level of
      knowledge about diabetes mellitus, and particularly hypoglycaemia symptoms, was
      inadequate. Logistic regression analysis showed that knowledge about diabetes
      mellitus correlated with educational status and with follow-up in a diabetes
      clinic.

PMID- 16602472
TI  - Hepatitis B surface antibody response of household contacts of hepatitis B virus
      carriers in Palestine.
AB  - To evaluate the effectiveness of hepatitis B virus (HBV) vaccination of household
      contacts of HBV carriers in Tulkarm district, Palestine, quantitative hepatitis B
      surface (anti-HBs) antibody response in 161 household contacts was measured after
      vaccination. A seroprotective anti-HBs response (titre > or = 10 IU/L) was
      elicited in all vaccinated subjects. Of these 2.5% had titres of 10-99 IU/L,
      61.5% 100-999 IU/L and 36.0% > or = 1000 IU/L. The number of vaccination doses
      had no effect on the achievement of seroprotection. HBV infection was
      demonstrated in 13 cases and their anti-HBV titres were in the range 25-350 IU/L.

PMID- 16602471
TI  - Management of diabetic foot in a Jordanian hospital.
AB  - The effect of different antibiotics on the outcome of surgical care in the
      management of diabetic foot was investigated. We randomly allocated 100 patients
      with diabetic foot into one of four groups. Each patient's infection was graded
      (Wagner classification). All patients were offered the same surgical care but
      each group was assigned a different antibiotic. Hospital stay for the four groups
      ranged from 7 to 14 days. Five patients experienced complications from
      septicaemia; 15 patients underwent amputation; and five patients experienced
      temporary renal impairment. Careful consideration to the type of antibiotic used
      is essential.

PMID- 16602473
TI  - Epidemiology of malaria in New Halfa, an irrigated area in eastern Sudan.
AB  - A prospective study investigated the epidemiology of malaria in an agricultural
      area in eastern Sudan from November 1999 to June 2000 (1 irrigation and 1 dry
      season). In monthly parasite surveys, 99/ 1539 blood films from 190 individuals
      were positive for malaria: 95% for Plasmodium falciparum, 3% P. vivax and 2% P.
      ovale. The slide positive rate (SPR) of malaria episodes ranged from 3.7% to
      12.8% in different months of the survey, with a peak in January. There was no
      significant difference in SPR between irrigation and dry seasons (7.2% versus
      5.1%). SPR differed significantly by age group and was highest in under 5-year
      olds. However, there was no significant difference in SPR between males and
      females. Transmission and intensity of malaria in this area is perennial and
      moderate rather than low.

PMID- 16602474
TI  - Urinary tract infection among pregnant women in Al-Mukalla district, Yemen.
AB  - Urinary tract infection (UTI) is a common problem in pregnant woman. This study
      examined the frequency of UTI in 137 pregnant women attending Al Mukalla
      maternity hospital from January to June 2002. Urine samples were examined for UTI
      microscopically and by culture, and sensitivity tests were done for the organisms
      isolated using a range of antibiotics. Information on age, trimester, parity and
      number of pregnancies were also collected for each woman. This study showed that
      30% of the women suffered from UTI; Escherichia coli was the most frequently
      isolated organism (41.5%), and it was highly susceptible to chloramphenicol,
      ciprofloxacin, ceftizoxime and amikacin. Of the variables examined, 53.7% of the
      infected women were in the age group 15-24 years, 48.8% were in their 3rd
      trimester and 75.6% had 1-3 children.

PMID- 16602475
TI  - Prevalence of Pityrosporum orbiculare on normal skin of Iraqi children.
AB  - To determine the age incidence and prevalence of Pityrosporum orbiculare on the
      normal skin of healthy Iraqi children, we carried out a survey of clinically
      normal skin of 110 healthy children in Baghdad during April 1998-October 1998. We
      isolated P. orbiculare on a peptone--glucose--yeast extract medium containing
      chloramphenicol and cycloheximide, and overlaid with olive oil. The organism was
      present on the trunk in 77.5% of children 10-14 years, 27.5% of children 5-9
      years, and 6.6% of children < 5 years.

PMID- 16602476
TI  - ECG of the month. Dyspnea and palpitations 16 years after tricuspid and aortic
      valve replacement. Atrial tachycardia (possibly slow atrial flutter) with 4:3
      type I (Wenckebach) atrioventricular block, right bundle branch block, and left
      anterior fascicular block.

PMID- 16602477
TI  - Radiology case of the month. Palmar mass and finger weakness. Fibrolipomatous
      hamartoma.

PMID- 16602478
TI  - Pathology case of the month. Elderly man with pancytopenia. Bone marrow
      granulomas secondary to amiodarone.

PMID- 16602479
TI  - Clinical case of the month. Furuncular myiasis.
AB  - A case of furuncular myiasis is reported. The life cycle of the parasite,
      differential diagnosis, host response, and therapy are briefly discussed.

PMID- 16602480
TI  - "Cut them into little stars".
AB  - The following are excerpts from testimony given in favor of House Bill 849 before
      the Ways and Means Committee of the Louisiana House of Representatives on June 7,
      2005. The bill asked for funding of a time sensitive illness and Homeland
      Security Emergency System for the State of Louisiana. Bill 849 was defeated by a
      vote of 9 - 2 in committee but subsequently rudimentary funding was secured in
      the joint conference committee of the House and Senate by Senate President Dr.
      Donald Hines. The prophetic poignancy of this plea and of so many other missed
      opportunities through the years should never be lost on the citizens of
      Louisiana.

PMID- 16602481
TI  - Graft-versus-host disease: case report and review of literature.
AB  - We describe a young patient with acute myeloid leukemia who, having been treated
      with allogenic hematopoietic stem cell transplantation, presented with acute
      graft-versus-host disease. One year later, leukemia relapse was treated with
      donor lymphocyte infusion and was followed by a new episode of acute graft-versus
      host disease. The patient died 18 months after the transplantation, with evidence
      of chronic graft-versus-host disease in multiple organs.

PMID- 16602482
TI  - Lunar Society and the discovery of digitalis.
AB  - William Withering was an established member of the renowned Lunar Society as well
      as an accomplished physician and botanist. Withering was an obsessive note taker
      and had a compulsion to observe and record. At the time when bleeding was the
      most common form of treatment for "dropsy", Withering's discovery of the foxglove
      and his detailed description of its medicinal purposes represented a major
      advance in the treatment of patients with heart failure. Withering's scrupulous
      account of the foxglove's potential for treating conditions of the heart was
      derived from dedicated study, experimentation, and deep concern for detail. The
      publication of "An Account of the Foxglove, and Some of its Medical Uses: with
      practical remarks on dropsy, and other diseases" marks a defining moment in the
      history of medicine.

PMID- 16602483
TI  - Role of imaging in the diagnosis of the superior mesenteric artery syndrome.
AB  - The purpose of this report is to describe the role of imaging in the diagnosis of
      the superior mesenteric artery syndrome. A review of clinical symptoms,
      diagnostic imaging, and patient management of superior mesenteric artery syndrome
      constitutes the core of this report. Images of upper gastrointestinal series,
      multislice CT, and CT angiography with multiplanar reconstruction illustrate
      their usefulness in the diagnosis of 3 patients with superior mesenteric artery
      syndrome.

PMID- 16602484
TI  - Omental torsion mimicking acute appendicitis: a case report.
AB  - Primary omental torsion is an uncommon cause of an acute abdomen that can mimic
      acute appendicitis. Herein we report a case of suspected acute appendicitis that
      proved to be a distal segment of infarcted omentum secondary to primary torsion.

PMID- 16602485
TI  - August Weismann's theory of the germ-plasm and the problem of unconceived
      alternatives.
AB  - I have argued elsewhere that scientific realism is most significantly challenged
      neither by traditional arguments from underdetermination of theories by the
      evidence, nor by the traditional pessimistic induction, but by a rather different
      historical pattern: our repeated failure to conceive of alternatives to extant
      scientific theories, even when those alternatives were both (1) well-confirmed by
      the evidence available at the time and (2) sufficiently scientifically serious as
      to be later embraced by actual scientific communities. Here I use August
      Weismann's defense of his influential germ-plasm theory of inheritance to support
      my claim that this pattern characterizes the history of theoretical scientific
      investigation generally. Weismann believed that the germ-plasm must become
      disintegrated into its constituent elements over the course of development, I
      argue, only because he failed to conceive of any possible alternative mechanism
      of ontogenetic differentiation. This and other features of the germ-plasm theory,
      I suggest, reflect a still more fundamental failure to imagine that the germ
      plasm might be a productive rather than expendable resource for the cell.
      Weismann's case provides impressive support for the problem of unconceived
      alternatives while rendering its challenge to scientific realism deeper and
      sharper in a number of important ways.

PMID- 16602486
TI  - Pathocoenoses ancient and modern.
AB  - Problems concerning the concept of biocoenosis in ecology (the antecedent of the
      pathocoenosis concept) are discussed first of all. Six main problems are
      identified: the problem of emergent properties of ecological communities; the
      problem of ambiguity; the problem of heterogeneity; the boundary problem; the
      problem of retrospective differential diagnosis; and the problem of explaining
      change over time. The rest of the paper gives illustrations of these problems in
      relation to human pathogens drawn mainly from the interactions of malaria with
      other diseases, particularly but not exclusively in the Mediterranean world, from
      antiquity through to modern times.

PMID- 16602487
TI  - [Wilhelm Troll (1897-1978). The tradition of idealistic morphology in the German
      botanical sciences of the 20th century].
AB  - During the first half of the 19th century, idealistic morphology developed into
      an influential research program in the German biosciences. This program was based
      on the concept of an ideal connection existing between various living beings. The
      growth of Darwinian thought and its new paradigm of historical explanation
      supplanted the idealistic morphology. Yet in the first half of the 20th century
      the principles of idealistic morphology experienced a powerful revival. Wilhelm
      Troll (1897-1978) was one of the most significant figures in this renaissance.
      Guided by the ideas of J.W. von Goethe, Troll established a research program
      rejecting causal, functional, and phylogenetic explanations as well as the idea
      of evolutionary adaptation. Instead, he attempted to create a 'pure' morphology
      based on the descriptions of various plant species. Governed by some explicitly
      metaphysical presumptions, Troll based his theory on the description of the
      organismal Gestalt. In consequence, his theory was actually a return to the
      proper idealistic morphology as it was known in the early 19th century. It lead
      German botanical morphology to a period of methodological and epistemological
      return.

PMID- 16602488
TI  - Natural selection and the conditions for existence: representational vs.
      conditional teleology in biological explanation.
AB  - Human intentional action, including the design and use of artifacts, involves the
      prior mental representation of the goal (end) and the means to achieve that goal.
      This representation is part of the efficient cause of the action, and thus can be
      used to explain both the action and the achievement of the end. This is
      intentional teleological explanation. More generally, teleological explanation
      that depends on the real existence of a representation of the goal (and the means
      to achieve it) can be called representational teleological explanation. Such
      explanations in biology can involve both external representations (e.g., ideas in
      the mind of God) and internal representations (souls, vital powers, entelechies,
      developmental programs, etc.). However, another type of explanation of
      intentional action (or any other process) is possible. Given that an action
      achieving a result occurs, the action can be explained as fulfilling the
      necessary conditions (means) for that result (end), and, reciprocally, the result
      explained by the occurrence of those necessary conditions. This is conditional
      teleological explanation. For organisms, natural selection is often understood
      metaphorically as the designer, intentionally constructing them for certain ends.
      Unfortunately, this metaphor is often taken rather too literally, because it has
      been difficult to conceive of another way to relate natural selection to the
      process of evolution. I argue that combining a conditional teleological
      explanation of organisms and of evolution provides such an alternative. This
      conditional teleology can be grounded in existence or survival. Given that an
      organism exists, we can explain its existence by the occurrence of the necessary
      conditions for that existence. This principle of the 'conditions for existence'
      was introduced by Georges Cuvier in 1800, and provides a valid, conditional
      teleological method for explaining organismal structure and behavior. From an
      evolutionary perspective, the conditions for existence are the range of boundary
      conditions within which the evolutionary process must occur. Moreover,
      evolutionary change itself can be subjected to conditional teleological
      explanation, because natural selection theory is primarily a theory about the
      relation between the conditions for the existence of organisms and the conditions
      for the existence of traits in populations. I show that failure to distinguish
      representational from conditional teleological explanation has confused previous
      attempts to clarify the relation of teleology to biology.

PMID- 16602489
TI  - Down in the mouth in Ancient Egypt.

PMID- 16602490
TI  - The Fairley collection.

PMID- 16602491
TI  - Dental dressers: 1920-1942.

PMID- 16602492
TI  - Sir John Lubbock--godfather to the dental profession.

PMID- 16602493
TI  - Recollections from the first ten years of dental practice: 1939-1949.

PMID- 16602494
TI  - I remember the dentist.

PMID- 16602496
TI  - Office-based sedation/anesthesia.

PMID- 16602498
TI  - Challenges in access to dental care for older Pennsylvanians and items for
      action.

PMID- 16602499
TI  - Looking through a window.

PMID- 16602500
TI  - The road map to guide patients from diagnosis to acceptance.

PMID- 16602502
TI  - A faculty of forensic and legal medicine at the Royal College of Physicians of
      London.

PMID- 16602501
TI  - Dental anesthesia requirements under the new regulations.

PMID- 16602503
TI  - Evidence, the law and the medical profession.

PMID- 16602505
TI  - Serious professional misconduct: fitness to practise.

PMID- 16602504
TI  - Refusal of interventions to protect the life of the viable fetus--a case-based
      Transatlantic overview.

PMID- 16602506
TI  - Reasons for the decision.

PMID- 16602507
TI  - Allocation of resources in the NHS.

PMID- 16602508
TI  - Having the operation done in Europe.

PMID- 16602509
TI  - Unfounded suspicion of child abuse.

PMID- 16602510
TI  - Future trends in military graduate medical education.
AB  - While on the surface the future of military GME appears uncertain, closer
      inspection demonstrates opportunities to achieve excellence in education. In many
      cases, programs will emerge with larger and more diverse faculty and increased
      collaboration with local institutions. On an individual level, military faculty
      will endeavor to blend teaching, research, and clinical excellence with unique
      operational opportunities and challenging assignments in and out of GME. The
      flexible and resourceful military physician can still count on an exciting and
      productive academic career.

PMID- 16602511
TI  - Physical medicine and rehabilitation in the military: Operation Iraqi Freedom.
AB  - This article describes the role of a physical medicine and rehabilitation
      (physiatry) physician (physiatrist) as a general medical officer within a forward
      support battalion during the invasion and nation-building phases of Operation
      Iraqi Freedom. Between March 10 and May 3, 2003 (invasion phase), 364 patients
      were evaluated. Thirty-two percent had musculoskeletal noncombat injuries, 9% had
      combat-related traumatic injuries, and the remaining 59% had
      nontrauma/nonmusculoskeletal conditions. Between May 4 and July 25, 2003 (nation
      building phase), 1,387 patients were evaluated. Of these, 19% had musculoskeletal
      injuries, 1% had combat-related traumatic injuries, and the remaining 80% had
      nontrauma/nonmusculoskeletal conditions. During this nation-building phase, the
      musculoskeletal workload seen at the division-level combat support hospital was 4
      times the workload seen in the forward support battalion. This experience
      underscores the role of physiatry in wartime casualty management and profiles the
      combat support hospital as the most suitable place for the physiatrist during
      wartime. Interventions focused on acute management and rehabilitation counseling
      for all musculoskeletal injuries, as well as consultation services to the combat
      support hospital and local civilian hospitals for the evaluation of complex
      neuromusculoskeletal trauma cases.

PMID- 16602512
TI  - Operation Enduring Freedom: the 48th Combat Support Hospital in Afghanistan.
AB  - OBJECTIVE: To examine the experience of the 48th Combat Support Hospital (CSH)
      while deployed to Afghanistan, with an emphasis on trauma care. MATERIALS AND
      METHODS: Before redeployment, a retrospective review was performed on the medical
      records of all patients treated at the 48th CSH from December 6, 2002 through
      June 7, 2003. RESULTS: During the 6-month period, 10,679 patients were evaluated
      and/or treated. There were 477 hospital admissions (adults, 387; children, 90;
      trauma, 204) and 634 operating room procedures. The most common mechanisms of
      injury were land mines/unexploded ordinance (74 = 36%) and gunshot wounds (41 =
      20%). Extremities were the most common site. A total of 358 cases was performed
      on 168 trauma patients (mean, 2 cases per patient; range, 1-12). There were 63
      complications in 40 trauma patients and 11 patients died. CONCLUSIONS: The 48th
      CSH supported military and humanitarian operations with an ongoing process of re
      evaluation, adaptation, and medical education that resulted in low morbidity and
      mortality rates.

PMID- 16602513
TI  - Radiology in a hostile environment: experience in Afghanistan.
AB  - Imaging equipment deployed with the combat support hospital in Afghanistan
      represented new technology not previously used in a hostile environment for a
      prolonged period. In general, the equipment performed well in a stationary
      location. Having computed tomography and ultrasound scans, in addition to plain
      radiographs, was very helpful for patient care. Redundancy of digital radiography
      and ultrasound systems proved prudent. It is recommended that a radiologist
      continue to be sent with the combat support hospital, particularly when computed
      tomography and ultrasound systems are in the deployment package. This report
      acquaints the medical community with information to aid in the planning and
      performance of future deployments that bring digital imaging to the battlespace.

PMID- 16602514
TI  - Process of care for battle casualties at Walter Reed Army Medical Center: Part I.
      Orthopedic surgery service.
AB  - Walter Reed Army Medical Center has been a primary hub in the United States for
      receiving Army battle casualties from Operation Enduring Freedom and Operation
      Iraqi Freedom. We detail the process of care that was developed to effect the
      timely effective management of these casualties.

PMID- 16602515
TI  - Process of care for battle casualties at Walter Reed Army Medical Center: Part
      II. Physical therapy service.
AB  - Physical therapists, physical therapy assistants, and physical therapy
      technicians provide care to soldiers, sailors, Marines, and airmen returning from
      Operation Enduring Freedom and Operation Iraqi Freedom. We describe the inpatient
      and outpatient services provided, the problems and solutions encountered, and the
      lessons learned at the beginning of the war.

PMID- 16602516
TI  - Process of care for battle casualties at the Walter Reed Army Medical Center:
      Part III. Physical medicine and rehabilitation service.
AB  - The Physical Medicine and Rehabilitation Service provides a critical role in the
      assessment, management, and disposition of the newly injured combatant. This role
      has been well demonstrated during Operation Enduring Freedom and Operation Iraqi
      Freedom. Military physiatrists are uniquely suited to support military service
      members as they maximize their function and either return to duty or transition
      to civilian life.

PMID- 16602517
TI  - Process of care for battle casualties at Walter Reed Army Medical Center: Part
      IV. Occupational therapy service.
AB  - Occupational therapy addresses deficits in activities of daily living, upper
      extremity motor performance deficits secondary to injury or disease, and
      occupational or role performance deficits attributable to mental and behavioral
      health conditions. We describe the inpatient and outpatient services provided,
      the problems and solutions encountered, and the lessons learned.

PMID- 16602518
TI  - Successful removal of a cerebellar hemangioblastoma in a combat support hospital.
AB  - The case of a 24-year-old male U.S. Marine Corps sergeant who presented with
      headache and ataxia to a combat support hospital (CSH) in Kuwait, during
      Operation Iraqi Freedom, is described. Imaging studies revealed a cystic brain
      neoplasm causing hydrocephalus and increased intracranial pressure. Because of
      the patient's deteriorating clinical condition and the high risk of further brain
      injury during a prolonged air evacuation flight, immediate surgery at the CSH was
      deemed the safest treatment option. The tumor was completely removed and the
      patient's symptoms resolved, allowing safe evacuation. A CSH is not intended to
      provide comprehensive neurosurgical capabilities and some equipment usually
      considered necessary to perform this surgery was unavailable, but field-expedient
      methods were devised to overcome these deficiencies. This is the first reported
      case of a brain tumor successfully removed in a CSH.

PMID- 16602519
TI  - Women's health care in Operation Iraqi Freedom: a survey of camps with echelon I
      or II facilities.
AB  - OBJECTIVE: To assess women's perceptions of health care delivery in Operation
      Iraqi Freedom. METHODS: An anonymous questionnaire was distributed through
      command channels to female soldiers stationed in camps receiving echelon I or II
      care. Questions covered predeployment screening, contraceptive method
      availability and side effects, accessibility of gynecologic care, field hygiene
      counseling, and smoking status. RESULTS: Two hundred fifty-one (91%) of 275
      surveys were returned. Twenty-two percent of respondents had received no annual
      gynecologic examination including the Papanicolaou test/cervical cytologic study
      in the past year. Irregular bleeding was the most common gynecologic side effect.
      Ortho Evra patches fell off in 58% of cases; 23% of soldiers changed
      contraceptive methods because of unavailability, 21% experienced gynecologic
      problems, and 44% could not access gynecologic care. Twenty-six percent received
      predeployment menstrual hygiene counseling, and 77% attempting cycle control
      succeeded. CONCLUSIONS: Gynecologic screening, contraceptive options, and cycle
      control counseling must occur before deployments. Specialty gynecologic care and
      medications for cycle control should be readily accessible to all female soldiers
      during deployments.

PMID- 16602521
TI  - Delayed drop zone evacuation: execution of the medical plan for an airborne
      operation into northern Iraq.
AB  - Flying directly from its home station in Vicenza, Italy, the 173rd Airborne
      Brigade committed itself to the invasion of Iraq on the night of March 26, 2003.
      Representing the establishment of a northern front, approximately 1,000
      paratroopers jumped into an isolated valley on a mission to secure and to hold
      the Bashur airstrip. This article describes the unique challenges of medical
      preparation for the mission, injuries sustained on the jump, and lessons learned.
      Emphasis is placed on the use of a policy of delayed evacuation until
      clarification of diagnosis.

PMID- 16602520
TI  - The beneficial relationship of the colocation of orthopedics and physical therapy
      in a deployed setting: Operation Iraqi Freedom.
AB  - In a deployment setting, orthopedic and musculoskeletal injuries represent the
      majority of both combat-related and noncombat-related injuries. To expeditiously
      and efficiently manage the large influx of patients, our experience revealed the
      tremendous benefits of having physical therapy colocated with an orthopedic
      surgeon in a level III combat support hospital. A physical therapist, working in
      a physician extender role, can treat the majority of nonsurgical orthopedic
      patients, thus allowing the orthopedic surgeon to focus his or her skills and
      time on surgical interventions. This physician extender role, although often
      overlooked during peacetime, becomes essential during wartime, when critically
      injured patients are abundant and physicians are in short supply. The lessons
      learned support the continued colocation of physical therapy and orthopedics in a
      deployment setting and recognize the need to have more physical therapists placed
      at level I and II echelons of care.

PMID- 16602522
TI  - Suicidal and homicidal soldiers in deployment environments.
AB  - Suicidal and homicidal soldiers present one of the most frequent and challenging
      scenarios for deployed mental health providers. A chart review of 425 deployed
      soldiers seen for mental health reasons found that 127 (nearly 30%) had
      considered killing themselves and 67 (nearly 16%) had considered killing someone
      else (not the enemy) within the past month. Of these, 75 cases were considered
      severe enough to require immediate intervention. Interventions included unit
      watch, comprehensive treatment, and medical evacuation. Of the 75 dangerous
      soldiers, 5 were evacuated out of theater. The rest were returned to duty.
      Evacuation to a hospital in the rear is often the quickest and most risk-free
      option but is seldom the best choice for maintaining the fighting force. This
      article presents several case examples and describes methods for dealing with
      suicidal and homicidal soldiers during deployment.

PMID- 16602523
TI  - Assessing risk propensity in American soldiers: preliminary reliability and
      validity of the Evaluation of Risks (EVAR) scale--English version.
AB  - Risk-taking propensity is a critical component of judgment and decision-making in
      military operations. The Evaluation of Risks scale (EVAR) was recently developed
      to measure state and trait aspects of risk proneness. The scale, however, was
      psychometrically normed in French and no data are available for the English
      translation. We administered the English version of the EVAR to 165 U.S. soldiers
      to obtain reliability, validity, and normative data for English-speaking
      respondents. Confirmatory factor analysis suggested that the factor structure of
      the English EVAR differs from that obtained in the French studies. Instead, a
      three-factor solution, including recklessness/impulsivity, self-confidence, and
      need for control, emerged. Internal consistency was comparable to the French
      version. EVAR scores correlated with age, military rank, and years of service,
      and discriminated soldiers with histories of high-risk behavior. The data support
      the reliability and validity of the English version of the EVAR for evaluating
      risk propensity in U.S. soldiers.

PMID- 16602524
TI  - Survey of U.S. Army commanders' experiences with brigade/battalion surgeons at
      Fort Hood, Texas.
AB  - This anonymous survey sent to every battalion and brigade commander at Fort Hood,
      Texas assessed the new concept of residency-trained operational physicians that
      had completed military unique curriculum series training. Commanders provided
      anonymous professional information about themselves and their assigned physicians
      and evaluated their physicians in 22 areas of medical and military competence
      using a linear scoring method from 2 (indicating poor) to 6 (indicating
      outstanding). Main effects and interaction effects were analyzed using multiple
      analysis of variance. The commanders' overall confidence in their physicians was
      5.4, suggesting general satisfaction. Prior-service physicians were rated higher
      on several factors if the commander had combat experience. Non-prior-service
      physicians were rated the same on nearly all variables regardless of the
      commander's experience. Commanders with combat experience rated their assigned
      physicians significantly higher than did commanders without combat experience.
      Despite high ratings, several candid remarks suggest there is still room for
      improvement.

PMID- 16602525
TI  - Wounding patterns for U.S. Marines and sailors during Operation Iraqi Freedom,
      major combat phase.
AB  - This investigation examined the wounds incurred by 279 U.S. Navy-Marine personnel
      (97% Marines and 3% sailors) identified as wounded in action during Operation
      Iraqi Freedom, from March 23 through April 30, 2003. The goal was to assess the
      potential impact of each causative agent by comparing the differences in
      anatomical locations, types of injuries caused, and medical specialists needed to
      treat the casualties. The overall average number of diagnoses per patient was
      2.2, and the overall average number of anatomical locations was 1.6. The
      causative agents were classified into six major categories, i.e., small arms,
      explosive munitions, motor vehicle accidents, falls, weaponry accidents, and
      other/unknown. Explosive munitions and small arms accounted for approximately
      three of four combat-related injuries. Upper and lower extremities accounted for
      approximately 70% of all injuries, a percentage consistent for battlefield
      injuries since World War II.

PMID- 16602526
TI  - The Neurocognition Deployment Health Study: a prospective cohort study of Army
      Soldiers.
AB  - Questions remain regarding the effects of military operational deployment on
      health. The Neurocognition Deployment Health Study addresses several gaps in the
      deployment health literature, including lack of baseline health data, reliance on
      subjective measures of exposure and health variables, prolonged intervals between
      redeployment and health assessments, and lack of a uniform case definition. The
      Neurocognition Deployment Health Study uses a prospective cohort design to assess
      neuropsychological outcomes associated with Iraq deployment. Methods incorporate
      administration of performance-based neuropsychological measures to Army soldiers
      before and after Iraq deployment and to nondeployed Army Soldiers assessed during
      comparable periods of garrison duty. Findings should have the potential to
      delineate neuropsychological outcomes related to combat theater deployment and to
      identify potential risk and protective factors related to health outcomes.

PMID- 16602527
TI  - Evaluation of field dental equipment in a deployment environment.
AB  - Dental officers and technicians must have reliable, durable, well-performing
      field dental equipment to enable them to provide dental care to deployed troops
      in operational environments. Unfortunately, no organized program exists to test
      such equipment before its purchase and use in the field. This article presents
      the results of a project conducted by the Naval Institute for Dental and
      Biomedical Research and the Air Force Dental Evaluation and Consultation Service
      to evaluate commercially available field dental equipment through laboratory
      testing and clinical-user evaluations in theater. The purpose of this 2-year
      project was to identify the best-performing and most cost-effective field dental
      equipment for possible future procurement. Initial laboratory testing was
      performed at the Naval Institute for Dental and Biomedical Research, and the
      equipment was then shipped to Kuwait for in-theater environmental and clinical
      user testing. A seven-member scientific team of military dental officers and
      technicians was deployed for 1 month to perform in-theater testing under regional
      environmental conditions and to coordinate clinical-user evaluations. The testing
      provided beneficial results by identifying equipment that performed properly and
      equipment that exhibited shortcomings serious enough to render it inadequate for
      operational use. It is recommended that the project serve as a model for future
      testing and evaluation of medical/dental equipment by all of the military
      services.

PMID- 16602528
TI  - The impact of predeployment training on Marine battalion manpower.

PMID- 16602529
TI  - Response to article: "Aeromedical evacuations from Operation Iraqi Freedom: a
      descriptive study" published in [Milit Med 2005; 170 (6):521-527].

PMID- 16602530
TI  - The boom goes on. Technology and consumer demands keep driving construction and
      renovation.
AB  - Facing a vastly outdated infrastructure, U.S. hospitals are undergoing their most
      significant expansion and facility replacement effort since World War II.
      Although the reasons and the focus of building projects vary, flexibility remains
      the watchword.

PMID- 16602531
TI  - Getting to the "C suite". What will it take to see diversity across health care
      leadership?
AB  - Although diversity in health care leadership has improved greatly over the past
      40 years, midcareer minorities still encounter a "glass ceiling" between director
      level jobs and the top four or five "chief" executive positions.

PMID- 16602532
TI  - Hospital-physician gainsharing.

PMID- 16602533
TI  - Characteristics of effective boards.
AB  - High-performing boards in all business sectors share many common traits: ongoing
      development; efficient, prioritized agendas; and solid structure and processes.
      Most important of all, however, is strong support from the top.

PMID- 16602534
TI  - Finances and access to capital: top agenda priorities.

PMID- 16602535
TI  - Information technology stewardship.

PMID- 16602536
TI  - The new chief medical officer: a bridge to your hospital's future.

PMID- 16602537
TI  - A patient's view of health IT.

PMID- 16602538
TI  - Intensivists: an Rx for the ICU?

PMID- 16602539
TI  - Getting a grip on costs and usage of spinal implant technologies.

PMID- 16602540
TI  - VHA launches project to transform OR's culture and clinical quality.

PMID- 16602541
TI  - Confrontation skills for OR business leaders.

PMID- 16602543
TI  - Spinal surgery: beyond the total disc.

PMID- 16602544
TI  - Higher costs with spinal 'fusion helpers'.

PMID- 16602542
TI  - Strategies for managing spinal implant costs.

PMID- 16602545
TI  - Turning around a cardiac surgery program.

PMID- 16602546
TI  - Creating a culture to improve retention.

PMID- 16602547
TI  - Eye center switches to all oral sedation.

PMID- 16602548
TI  - Study of perioperative med errors provides clues for improving care.

PMID- 16602549
TI  - Innovative approaches to turnover time.

PMID- 16602550
TI  - Strategies for preventing med errors.

PMID- 16602552
TI  - Teach-back improves informed consent.

PMID- 16602551
TI  - A positive approach to negative people.

PMID- 16602553
TI  - A call for better reprocessing instructions.

PMID- 16602554
TI  - Insurers heat up propofol controversy.

PMID- 16602555
TI  - Helen Young.

PMID- 16602556
TI  - Role modelling.

PMID- 16602557
TI  - Ups and downs.

PMID- 16602558
TI  - Acting the part.
AB  - The implementation of two key policies highlighted the need to support nurses and
      midwives to challenge colleagues effectively. To overcome the difficulties this
      presented, an innovative training package using drama provided participants with
      practical tips and a safe environment to practise newly developed skills. The
      programme was well evaluated but further work needs to be undertaken to evaluate
      its impact upon practice.

PMID- 16602559
TI  - Measuring and managing nursing quality.

PMID- 16602560
TI  - Piecing together the whole picture.

PMID- 16602561
TI  - Innovation and teamwork: introducing multidisciplinary team ward rounds.

PMID- 16602562
TI  - Leading in teams: part 1.

PMID- 16602563
TI  - Cardiac anisotropy: is it negligible regarding noninvasive activation time
      imaging?
AB  - The aim of this study was to quantify the effect of cardiac anisotropy in the
      activation-based inverse problem of electrocardiography. Differences of the
      patterns of simulated body surface potential maps for isotropic and anisotropic
      conditions were investigated with regard to activation time (AT) imaging of
      ventricular depolarization. AT maps were estimated by solving the nonlinear
      inverse ill-posed problem employing spatio-temporal regularization. Four
      different reference AT maps (sinus rhythm, right-ventricular and septal pacing,
      accessory pathway) were calculated with a bidomain theory based anisotropic
      finite-element heart model in combination with a cellular automaton. In this
      heart model a realistic fiber architecture and conduction system was implemented.
      Although the anisotropy has some effects on forward solutions, effects on inverse
      solutions are small indicating that cardiac anisotropy might be negligible for
      some clinical applications (e.g., imaging of focal events) of our AT imaging
      approach. The main characteristic events of the AT maps were estimated despite
      neglected electrical anisotropy in the inverse formulation. The worst correlation
      coefficient of the estimated AT maps was 0.810 in case of sinus rhythm. However,
      all characteristic events of the activation pattern were found. The results of
      this study confirm our clinical validation studies of noninvasive AT imaging in
      which cardiac anisotropy was neglected.

PMID- 16602564
TI  - Modeling fibrillation potentials--a new analytical description for the muscle
      intracellular action potential.
AB  - The single-fiber action potential (SFAP) can be modeled as a convolution of a
      biolectrical source (the excitation) and a transfer function, representing the
      electrical volume conduction. In the Dimitrov-Dimitrova (D-D) convolutional
      model, the first temporal derivative of the intracellular action potential (IAP)
      is used as the source. In this model, the ratio between the amplitudes of the
      second and first phases of the SFAP (which we call the PPR, after peak-to-peak
      ratio) increases invariably with radial distance. This is not the case of real
      recorded fibrillation potentials (FPs). Moreover, FPs show a wider PPR range than
      that which the D-D model can provide. These discrepancies suggest that the D-D
      model should be revised. Since the volume conduction parameters seem to have no
      apparent effects on the PPR, we assume that the origin of this difference lies in
      the excitation source. This paper presents a new analytical description of the
      IAP based on that expressed in the D-D model. The new approximation is shown to
      model FPs with a range of PPRs comparable to that observed in a set of real FPs
      which we used as our test signals.

PMID- 16602565
TI  - A finite element model for describing the effect of muscle shortening on surface
      EMG.
AB  - A finite-element model for the generation of single fiber action potentials in a
      muscle undergoing various degrees of fiber shortening is developed. The muscle is
      assumed fusiform with muscle fibers following a curvilinear path described by a
      Gaussian function. Different degrees of fiber shortening are simulated by
      changing the parameters of the fiber path and maintaining the volume of the
      muscle constant. The conductivity tensor is adapted to the muscle fiber
      orientation. In each point of the volume conductor, the conductivity of the
      muscle tissue in the direction of the fiber is larger than that in the
      transversal direction. Thus, the conductivity tensor changes point-by-point with
      fiber shortening, adapting to the fiber paths. An analytical derivation of the
      conductivity tensor is provided. The volume conductor is then studied with a
      finite-element approach using the analytically derived conductivity tensor.
      Representative simulations of single fiber action potentials with the muscle at
      different degrees of shortening are presented. It is shown that the geometrical
      changes in the muscle, which imply changes in the conductivity tensor, determine
      important variations in action potential shape, thus affecting its amplitude and
      frequency content. The model provides a new tool for interpreting surface EMG
      signal features with changes in muscle geometry, as it happens during dynamic
      contractions.

PMID- 16602566
TI  - Enhancing the signal-to-noise ratio of ICA-based extracted ERPs.
AB  - When decomposing single trial electroencephalography it is a challenge to
      incorporate prior physiological knowledge. Here, we develop a method that uses
      prior information about the phase-locking property of event-related potentials in
      a regularization framework to bias a blind source separation algorithm toward an
      improved separation of single-trial phase-locked responses in terms of an
      increased signal-to-noise ratio. In particular, we suggest a transformation of
      the data, using weighted average of the single trial and trial-averaged response,
      that redirects the focus of source separation methods onto the subspace of event
      related potentials. The practical benefit with respect to an improved separation
      of such components from ongoing background activity and extraneous noise is first
      illustrated on artificial data and finally verified in a real-world application
      of extracting single-trial somatosensory evoked potentials from multichannel EEG
      recordings.

PMID- 16602567
TI  - Motor unit conduction velocity distribution estimation from evoked motor
      responses.
AB  - Action potentials travel along the muscle fibers with a specific conduction
      velocity that depends on their structural and functional properties. Only the
      estimation of muscle conduction velocity distribution (MCVD) may be able to
      depict this propagation heterogeneity. Based on the method proposed by Cummins et
      al. (Electroenceph Clin Neurophysiol, 46:647-658, 1979) to estimate nerve
      conduction velocity distribution (NCVD), the present paper proposes a method that
      modifies the Cummins' approach to make it suitable for MCVD estimation from
      electrically evoked motor responses. The MCVD estimation algorithm was first
      assessed by means of simulated signals in order to control all signal features
      during the optimization process. Simulations showed that estimated distributions
      were very close to the true ones when taking into account the specificities of
      the muscle action potential, due to its generation and extinction (MSE divided by
      5 on distribution standard deviation). This method was then applied to real
      signals. Elicited motor responses were recorded on the biceps brachii of healthy
      subjects either during repeated maximal stimulations at 20 Hz or during
      increasing intensity stimulations at 1 Hz. MCVD estimates were used to analyze
      fatigue and motor unit recruitment processes, respectively.

PMID- 16602568
TI  - Quantifying cortical activity during general anesthesia using wavelet analysis.
AB  - This paper reports on a novel method for quantifying the cortical activity of a
      patient during general anesthesia as a surrogate measure of the patient's level
      of consciousness. The proposed technique is based on the analysis of a single
      channel (frontal) electroencephalogram (EEG) signal using stationary wavelet
      transform (SWT). The wavelet coefficients calculated from the EEG are pooled into
      a statistical representation, which is then compared to two well-defined states:
      the awake state with normal EEG activity, and the isoelectric state with maximal
      cortical depression. The resulting index, referred to as the wavelet-based
      anesthetic value for central nervous system monitoring (WAV(CNS)), quantifies the
      depth of consciousness between these two extremes. To validate the proposed
      technique, we present a clinical study which explores the advantages of the
      WAV(CNS) in comparison with the BIS monitor (Aspect Medical Systems, MA),
      currently a reference in consciousness monitoring. Results show that the WAV(CNS)
      and BIS are well correlated (r = 0.969) during periods of steady-state despite
      fundamental algorithmic differences. However, in terms of dynamic behavior, the
      WAV(CNS) offers faster tracking of transitory changes at induction and emergence,
      with an average lead of 15-30 s. Furthermore, and conversely to the BIS, the
      WAV(CNS) regains its preinduction baseline value when patients are responding to
      verbal command after emergence from anesthesia. We conclude that the proposed
      analysis technique is an attractive alternative to BIS monitoring. In addition,
      we show that the WAV(CNS) dynamics can be modeled as a linear time invariant
      transfer function. This index is, therefore, well suited for use as a feedback
      sensor in advisory systems, closed-loop control schemes, and for the
      identification of the pharmacodynamic models of anesthetic drugs.

PMID- 16602569
TI  - Detection of pseudosinusoidal epileptic seizure segments in the neonatal EEG by
      cascading a rule-based algorithm with a neural network.
AB  - This paper presents an approach to detect epileptic seizure segments in the
      neonatal electroencephalogram (EEG) by characterizing the spectral features of
      the EEG waveform using a rule-based algorithm cascaded with a neural network. A
      rule-based algorithm screens out short segments of pseudosinusoidal EEG patterns
      as epileptic based on features in the power spectrum. The output of the rule
      based algorithm is used to train and compare the performance of conventional
      feedforward neural networks and quantum neural networks. The results indicate
      that the trained neural networks, cascaded with the rule-based algorithm,
      improved the performance of the rule-based algorithm acting by itself. The
      evaluation of the proposed cascaded scheme for the detection of pseudosinusoidal
      seizure segments reveals its potential as a building block of the automated
      seizure detection system under development.

PMID- 16602570
TI  - A comparison of common spatial patterns with complex band power features in a
      four-class BCI experiment.
AB  - We report on the offline analysis of four-class brain-computer interface (BCI)
      data recordings. Although the analysis is done within defined time windows (cue
      based BCI), our goal is to work toward an approach which classifies on-going
      electroencephalogram (EEG) signals without the use of such windows (un-cued BCI).
      To that end, we provide some elements of that analysis related to timing issues
      that will become important as we pursue this goal in the future. A new set of
      features called complex band power (CBP) features which make explicit use of
      phase are introduced and are shown to produce good results. As reference methods
      we used traditional band power features and the method of common spatial
      patterns. We consider also for the first time in the context of a four-class
      problem the issue of variability of the features over time and how much data is
      required to give good classification results. We do this in a practical way where
      training data precedes testing data in time.

PMID- 16602571
TI  - Efficient localization of synchronous EEG source activities using a modified RAP
      MUSIC algorithm.
AB  - Synchronization across different brain regions is suggested to be a possible
      mechanism for functional integration. Noninvasive analysis of the synchronization
      among cortical areas is possible if the electrical sources can be estimated by
      solving the electroencephalography inverse problem. Among various inverse
      algorithms, spatio-temporal dipole fitting methods such as RAP-MUSIC and R-MUSIC
      have demonstrated superior ability in the localization of a restricted number of
      independent sources, and also have the ability to reliably reproduce temporal
      waveforms. However, these algorithms experience difficulty in reconstructing
      multiple correlated sources. Accurate reconstruction of correlated brain
      activities is critical in synchronization analysis. In this study, we modified
      the well-known inverse algorithm RAP-MUSIC to a multistage process which analyzes
      the correlation of candidate sources and searches for independent topographies
      (ITs) among precorrelated groups. Comparative studies were carried out on both
      simulated data and clinical seizure data. The results demonstrated superior
      performance with the modified algorithm compared to the original RAP-MUSIC in
      recovering synchronous sources and localizing the epileptiform activity. The
      modified RAP-MUSIC algorithm, thus, has potential in neurological applications
      involving significant synchronous brain activities.

PMID- 16602572
TI  - A robust method for estimating respiratory flow using tracheal sounds entropy.
AB  - The relationship between respiratory sounds and flow is of great interest for
      researchers and physicians due to its diagnostic potentials. Due to difficulties
      and inaccuracy of most of the flow measurement techniques, several researchers
      have attempted to estimate flow from respiratory sounds. However, all of the
      proposed methods heavily depend on the availability of different rates of flow
      for calibrating the model, which makes their use limited by a large degree. In
      this paper, a robust and novel method for estimating flow using entropy of the
      band pass filtered tracheal sounds is proposed. The proposed method is novel in
      terms of being independent of the flow rate chosen for calibration; it requires
      only one breath for calibration and can estimate any flow rate even out of the
      range of calibration flow. After removing the effects of heart sounds (which
      distort the low-frequency components of tracheal sounds) on the calculated
      entropy of the tracheal sounds, the performance of the method at different
      frequency ranges were investigated. Also, the performance of the proposed method
      was tested using 6 different segment sizes for entropy calculation and the best
      segment sizes during inspiration and expiration were found. The method was tested
      on data of 10 healthy subjects at five different flow rates. The overall
      estimation error was found to be 8.3 +/- 2.8% and 9.6 +/- 2.8% for inspiration
      and expiration phases, respectively.

PMID- 16602574
TI  - Multiexpert automatic speech recognition using acoustic and myoelectric signals.
AB  - Classification accuracy of conventional automatic speech recognition (ASR)
      systems can decrease dramatically under acoustically noisy conditions. To improve
      classification accuracy and increase system robustness a multiexpert ASR system
      is implemented. In this system, acoustic speech information is supplemented with
      information from facial myoelectric signals (MES). A new method of combining
      experts, known as the plausibility method, is employed to combine an acoustic ASR
      expert and a MES ASR expert. The plausibility method of combining multiple
      experts, which is based on the mathematical framework of evidence theory, is
      compared to the Borda count and score-based methods of combination. Acoustic and
      facial MES data were collected from 5 subjects, using a 10-word vocabulary across
      an 18-dB range of acoustic noise. As expected the performance of an acoustic
      expert decreases with increasing acoustic noise; classification accuracies of the
      acoustic ASR expert are as low as 11.5%. The effect of noise is significantly
      reduced with the addition of the MES ASR expert. Classification accuracies remain
      above 78.8% across the 18-dB range of acoustic noise, when the plausibility
      method is used to combine the opinions of multiple experts. In addition, the
      plausibility method produced classification accuracies higher than any individual
      expert at all noise levels, as well as the highest classification accuracies,
      except at the 9-dB noise level. Using the Borda count and score-based multiexpert
      systems, classification accuracies are improved relative to the acoustic ASR
      expert but are as low as 51.5% and 59.5%, respectively.

PMID- 16602573
TI  - Monotonicity of approximate entropy during transition from awareness to
      unresponsiveness due to propofol anesthetic induction.
AB  - The ability to monitor the physiological effects of sedative medication
      accurately is of interest in clinical practice. During the anesthetic agent
      driven transition to unresponsiveness, nonstationary changes such as signal
      amplitude variations appear in electroencephalography. In this paper, it is
      studied whether the application of the approximate entropy (ApEn) method to
      electroencephalographic (EEG) signal produces a monotonic response curve during
      the transition from awareness to unresponsiveness. Data from fourteen patients,
      undergoing propofol anesthetic induction were studied. To optimize the ApEn
      performance, different parameter choices were carefully evaluated. It was assumed
      with our protocol, that the level of anesthesia changes monotonically with the
      elapsed induction time. The monotonicity of the ApEn change was assessed with the
      prediction probability statistic (PK). The monotonicity of the ApEn time-series
      depends on the parameters employed in the algorithm and the varying signal
      amplitude. Depending on the parameter values, the median PK value ranged from
      0.886 to 0.527. Thus, a good directionality and concordance was observed, but the
      nonstationarity of the signal affected the results. In conclusion, EEG-based ApEn
      measure shows a nonlinear response during propofol induction. With a judicious
      choice of parameters, a monotonic response is confirmed using PK statistic.

PMID- 16602575
TI  - Center of mass approximation and prediction as a function of body acceleration.
AB  - In order to maintain postural stability, the central nervous system must maintain
      equilibrium of the total center of body mass (COM) in relation to its base of
      support. Thus, the trajectory of the COM provides an important measure of
      postural stability. Three different models were developed to estimate the COM and
      the results tested on 16 subjects: namely a neural network, an adaptive fuzzy
      interface system and a hybrid genetic algorithm sum-of-sines model. The inputs to
      the models were acquired via two accelerometers, one representing the trunk
      segment placed on T2 and the second representing the limb segment placed on the
      shank below the knee joint. The portability, ease of use and low cost (compared
      with video motion analysis systems) of the accelerometers increases the range of
      clinics to which the system will be available. The subjects performed a
      multisegmental movement task on fixed and foam surfaces, thus covering a
      relatively wide dynamic scope. The results are encouraging for obtaining COM
      estimates that have clinical applications; the genetic sum-of-sines model was
      found to be superior when compared to the other two models.

PMID- 16602576
TI  - Fatigue estimation with a multivariable myoelectric mapping function.
AB  - A novel approach to muscle fatigue assessment is proposed. A function is used to
      map multiple myoelectric parameters representing segments of myoelectric data to
      a fatigue estimate for that segment. An artificial neural network is used to tune
      the mapping function and time-domain features are used as inputs. Two fatigue
      tests were conducted on five participants in each of static, cyclic and random
      conditions. The function was tuned with one data set and tested on the other.
      Performance was evaluated based on a signal to noise metric which compared
      variability due to fatigue factors with variability due to nonfatiguing factors.
      Signal to noise ratios for the mapping function ranged from 7.89 under random
      conditions to 9.69 under static conditions compared to 3.34-6.74 for mean
      frequency and 2.12-2.63 for instantaneous mean frequency indicating that the
      mapping function tracks the myoelectric manifestations of fatigue better than
      either mean frequency or instantaneous mean frequency under all three contraction
      conditions.

PMID- 16602577
TI  - Characterization of repolarization alternans during ischemia: time-course and
      spatial analysis.
AB  - T-wave alternans (TWA) has been linked to increased vulnerability to ventricular
      fibrillation in different settings including myocardial ischemia. In this study,
      we propose a methodology for the characterization of TWA induced by transient,
      regional ischemia. We studied the prevalence, magnitude and spatio-temporal
      relationship between TWA and ischemia in 95 patients undergoing percutaneous
      transluminal coronary angioplasty (PTCA). Two electrocardiogram records of each
      patient, a control recording before PTCA and the PTCA record, were analyzed using
      a robust, recently proposed method for TWA analysis. The detected episodes were
      characterized in terms of their time-course, lead distribution and alternans
      waveform. One third of the patients (33.7%) showed TWA episodes during PTCA. The
      highest prevalence (51.7%) and amplitude were found in patients with left
      anterior descendent artery occlusion. The onset of TWA was detected after the
      first 1-2 min of occlusion, suggesting that some level of ischemia must be
      attained before TWA arises, while disappearance of TWA following reperfusion was
      much more rapid. The TWA lead distributions and waveforms showed distinct
      distributions according to the occluded artery reflecting the regional nature of
      the TWA phenomenon.

PMID- 16602578
TI  - Improving EMG-based muscle force estimation by using a high-density EMG grid and
      principal component analysis.
AB  - The accuracy of predictions of muscle force based on electromyography (EMG) is an
      important issue in biomechanics and kinesiology. Since human skeletal muscles
      show a high diversity and heterogeneity in their fiber architecture, it is
      difficult to properly align electrodes to the muscle fiber direction. Against
      this background, we analyzed the effect of different bipolar configuration
      directions on EMG-based force estimation. In addition, we investigated whether
      principal component analysis (PCA) can improve this estimation. High-density
      surface-EMG from the triceps brachii muscle and the extension force of the elbow
      were measured in 11 subjects. The root mean square difference (RMSD) between
      predicted and measured force was determined. We found the best bipolar
      configuration direction to cause a 13% lower RMSD relative to the worst
      direction. Optimal results were obtained with electrodes aligned with the
      expected main muscle fiber direction. We found that PCA reduced RMSD by about 40%
      compared to conventional bipolar electrodes and by about 12% compared to
      optimally aligned multiple bipolar electrodes. Thus, PCA contributes to the
      accuracy of EMG-based estimation of muscle force when using a high-density EMG
      grid.

PMID- 16602579
TI  - Improved field localization in transcranial magnetic stimulation of the brain
      with the utilization of a conductive shield plate in the stimulator.
AB  - In this paper, a carefully designed conductive shield plate is presented, which
      helps to improve localization of the electric field distribution induced by
      transcranial magnetic stimulation for neuron stimulation. The shield plate is
      introduced between a figure-of-eight coil and the head. In order to accurately
      predict the field distribution inside the brain and to examine the effects of the
      shield plate, a realistic head model is constructed from magnetic resonance image
      data with the help of image processing tools and the finite-element method in
      three dimensions is employed. Finally, to show the improvements obtained, the
      results are compared with two conventional coil designs. It is found that an
      incorporation of the shield plate into the coil, effectively improves the induced
      field localization by more than 50%, and prevents other parts of the brain from
      exposure to high pulsed magnetic fields.

PMID- 16602580
TI  - Microelectrode array for chronic deep-brain microstimulation and recording.
AB  - We have developed an array of microelectrodes that is suitable for long-term
      implantation into the subthalamic nucleus (STN) or the globus pallidus and is
      able to record from single neurons, as well as deliver localized
      microstimulation. This device can be used to investigate the mechanisms by which
      deep brain stimulation can ameliorate the symptoms of Parkinson's disease and
      other movement disorders, and also may be the basis for a new clinical tool for
      the treatment of Parkinson's disease, by capitalizing on the high spatial
      specificity of intranuclear microstimulation. The array includes 16 activated
      iridium microelectrodes, 5-6 mm in length, within a cluster approximately 1.8 mm
      in diameter. We have fabricated the array using materials carrying the USP
      Category VI classification, and we have developed an apparatus and a procedure
      for implanting the microelectrode arrays into the deep brain. Ten arrays have
      been implanted into the STN of domestic cats, and one into the internal segment
      of the globus pallidus, for 140-415 days. During that time, we were able to
      record action potentials from individual neurons, on 4 to 8 of the 16 channels.
      The microelectrode' active surface areas ranged from 500 to 2000 microm2.
      Controlled-current pulses, 26.5 microA in amplitude and 150 micros/phase in
      duration (4 nC/phase) were used to excite neurons in the cat's STN. In addition
      to direct activation, the stimulus modulated the neuronal activity over a
      distance of at least 1.2 mm from the site of stimulation. These parameters did
      not induce histologically detectable changes around the tip sites after 35 hours
      of stimulation at 100 Hz (7 hours of stimulation per day, on 5 successive days),
      if the electrode' active surface area was 1000 microm2 or greater.

PMID- 16602581
TI  - A new action potential detector using the MTEO and its effects on spike sorting
      systems at low signal-to-noise ratios.
AB  - This paper considers neural signal processing applied to extracellular
      recordings, in particular, unsupervised action potential detection at a low
      signal-to-noise ratio. It adopts the basic framework of the multiresolution
      Teager energy operator (MTEO) detector, but presents important new results
      including a significantly improved MTEO detector with some mathematical analyses,
      a new alignment technique with its effects on the whole spike sorting system, and
      a variety of experimental results. Specifically, the new MTEO detector employs
      smoothing windows normalized by noise power derived from mathematical analyses
      and has an improved complexity by utilizing the sampling rate. Experimental
      results prove that this detector achieves higher detection ratios at a fixed
      false alarm ratio than the TEO detector and the discrete wavelet transform
      detector. We also propose a method that improves the action potential alignment
      performance. Observing that the extreme points of the MTEO output are more robust
      to the background noise than those of the action potentials, we use the MTEO
      output for action potential alignment. This brings not only noticeable
      improvement in alignment performance but also quite favorable influence over the
      classification performance. Accordingly, the proposed detector improves the
      performance of the whole spike sorting system. We verified the improvement using
      various modeled neural signals and some real neural recordings.

PMID- 16602582
TI  - Influence of glycerol on the mechanical reversibility and thermal damage
      susceptibility of collagenous tissues.
AB  - Clinical procedures wherein supraphysiologic temperatures must be achieved in
      deep layers of tissue via light are often compromised by optical scattering and
      absorption. Optical clearing of tissue superficial to the target improves the
      efficacy of such procedures. Glycerol is an attractive chemical agent for
      achieving dramatic reductions in tissue turbidity, but its net effects on healthy
      tissue are not fully understood. In this paper, we investigate possible
      alterations of biaxial mechanical properties in a model collagenous tissue,
      bovine epicardium, induced by glycerol. Furthermore, we examine the effects of
      glycerol on the biaxial thermomechanical properties of epicardium constrained at
      near-physiologic length. It is seen that mechanical changes induced by glycerol
      are fully reversed upon rehydration in normal saline. Moreover, glycerol protects
      cleared tissue by increasing its thermal stability and minimizing thermal
      alterations of mechanical properties.

PMID- 16602583
TI  - The use of the fractional Fourier transform with coded excitation in ultrasound
      imaging.
AB  - Medical ultrasound systems are limited by a tradeoff between axial resolution and
      the maximum imaging depth which may be achieved. The technique of coded
      excitation has been used extensively in the field of RADAR and SONAR for some
      time, but has only relatively recently been exploited in the area of medical
      ultrasound. This technique is attractive because allows the relationship between
      the pulse length and the maximum achievable spatial resolution to be changed. The
      work presented here explores the possibility of using the fractional Fourier
      transform as an effective means for the processing of signals received after the
      transmission of linear frequency modulated chirps. Results are presented which
      demonstrate that this technique is able to offer spatial resolutions similar to
      those obtained with a single cycle duration signal.

PMID- 16602584
TI  - Integrate-and-fire model for electrically stimulated nerve cell.
AB  - A commonly used simple spiking cell model is modified for extracellular current
      activation. It is proposed to simplify the simulation of a myelinated fiber nerve
      cell at the electrode-tissue interface by substituting for the activation site(s)
      identified with a more complex neuron model.

PMID- 16602585
TI  - In vivo registration of both electrogoniometry and medical imaging: development
      and application on the ankle joint complex.
AB  - An in vivo method for joint kinematics visualization and analysis is described.
      Low-dose computed tomography allowed three-dimensional joint modeling, and
      electrogoniometry collected joint kinematic data. Data registration occurred
      using palpated anatomical landmarks to obtain interactive computer joint
      simulation. The method was applied on one volunteer's ankle, and reproducibility
      was tested (maximal discrepancy: 3.6 deg and 5.5 mm for rotation and translation
      respectively).

PMID- 16602586
TI  - Automated segmentation, classification, and tracking of cancer cell nuclei in
      time-lapse microscopy.
AB  - Quantitative measurement of cell cycle progression in individual cells over time
      is important in understanding drug treatment effects on cancer cells. Recent
      advances in time-lapse fluorescence microscopy imaging have provided an important
      tool to study the cell cycle process under different conditions of perturbation.
      However, existing computational imaging methods are rather limited in analyzing
      and tracking such time-lapse datasets, and manual analysis is unreasonably time
      consuming and subject to observer variances. This paper presents an automated
      system that integrates a series of advanced analysis methods to fill this gap.
      The cellular image analysis methods can be used to segment, classify, and track
      individual cells in a living cell population over a few days. Experimental
      results show that the proposed method is efficient and effective in cell tracking
      and phase identification.

PMID- 16602587
TI  - Using recurrence quantification analysis determinism for noise removal in cardiac
      optical mapping.
AB  - Selecting signal processing parameters in optical imaging by utilizing the change
      in Determinism, a measure introduced in Recurrence Quantification Analysis,
      provides a novel method using the change in residual noise Determinism for
      improving noise quantification and removal across signals exhibiting disparate
      underlying tissue pathologies. The method illustrates an improved process for
      selecting filtering parameters and how using measured signal-to-noise ratio alone
      can lead to improper parameter selection.

PMID- 16602588
TI  - A stable learning algorithm for block-diagonal recurrent neural networks:
      application to the analysis of lung sounds.
AB  - A novel learning algorithm, the Recurrent Neural Network Constrained Optimization
      Method (RENNCOM) is suggested in this paper, for training block-diagonal
      recurrent neural networks. The training task is formulated as a constrained
      optimization problem, whose objective is twofold: (1) minimization of an error
      measure, leading to successful approximation of the input/output mapping and (2)
      optimization of an additional functional, the payoff function, which aims at
      ensuring network stability throughout the learning process. Having assured the
      network and training stability conditions, the payoff function is switched to an
      alternative form with the scope to accelerate learning. Simulation results on a
      benchmark identification problem demonstrate that, compared to other learning
      schemes with stabilizing attributes, the RENNCOM algorithm has enhanced
      qualities, including, improved speed of convergence, accuracy and robustness. The
      proposed algorithm is also applied to the problem of the analysis of lung sounds.
      Particularly, a filter based on block-diagonal recurrent neural networks is
      developed, trained with the RENNCOM method. Extensive experimental results are
      given and performance comparisons with a series of other models are conducted,
      underlining the effectiveness of the proposed filter.

PMID- 16602589
TI  - Line of sight robot navigation toward a moving goal.
AB  - In this paper, we consider the problem of robot tracking and navigation toward a
      moving goal. The goal's maneuvers are not a priori known to the robot. Thus, off
      line strategies are not effective. To model the robot and the goal, we use
      geometric rules combined with kinematics equations expressed in a polar
      representation. The intent of the strategy is to keep the robot between a
      reference point, called the observer, and the goal. We prove under certain
      assumptions that the robot navigating using this strategy reaches the moving goal
      successfully. In the presence of obstacles, the method is combined with an
      obstacle avoidance algorithm. The robot then moves in two modes, the navigation
      mode and the obstacle avoidance mode. Simulation of various scenarios highlights
      the efficiency of the method and provides an instructive comparison between the
      paths obtained for different reference points.

PMID- 16602590
TI  - An adaptive recurrent-neural-network motion controller for X-Y table in CNC
      machine.
AB  - In this paper, an adaptive recurrent-neural-network (ARNN) motion control system
      for a biaxial motion mechanism driven by two field-oriented control permanent
      magnet synchronous motors (PMSMs) in the computer numerical control (CNC) machine
      is proposed. In the proposed ARNN control system, a RNN with accurate
      approximation capability is employed to approximate an unknown dynamic function,
      and the adaptive learning algorithms that can learn the parameters of the RNN on
      line are derived using Lyapunov stability theorem. Moreover, a robust controller
      is proposed to confront the uncertainties including approximation error, optimal
      parameter vectors, higher-order terms in Taylor series, external disturbances,
      cross-coupled interference and friction torque of the system. To relax the
      requirement for the value of lumped uncertainty in the robust controller, an
      adaptive lumped uncertainty estimation law is investigated. Using the proposed
      control, the position tracking performance is substantially improved and the
      robustness to uncertainties including cross-coupled interference and friction
      torque can be obtained as well. Finally, some experimental results of the
      tracking of various reference contours demonstrate the validity of the proposed
      design for practical applications.

PMID- 16602591
TI  - Extraction of line segments and circular arcs from freehand strokes based on
      segmental homogeneity features.
AB  - The extraction of component line segments and circular arcs from freehand strokes
      along with their relations is a prerequisite for sketch understanding. Existing
      approaches usually take three stages to segment a stroke: first identifying
      segmentation points, then classifying the substroke between each pair of adjacent
      segmentation points, and, finally, obtaining graphical representations of
      substrokes by fitting graphical primitives to them. Since a stroke inevitably
      contains noises, the first stage may produce wrong or inaccurate segmentation
      points, resulting in the wrong substroke classification in the second stage and
      inaccurately fitted parameters in the third stage. To overcome the noise
      sensitivity of the three-stage method, the segmental homogeneity feature is
      emphasized in this paper. We propose a novel approach, which first extracts
      graphical primitives from a stroke by a connected segment growing from a seed
      segment and then utilizes relationships between the primitives to refine their
      control parameters. We have conducted experiments using real-life strokes and
      compared the proposed approach with others. Experimental results demonstrate that
      the proposed approach is effective and robust.

PMID- 16602592
TI  - On the ternary spatial relation "between".
AB  - The spatial relation "between" is a notion which is intrinsically both fuzzy and
      contextual, and depends, in particular, on the shape of the objects. The
      literature is quite poor on this and the few existing definitions do not take
      into account these aspects. In particular, an object B that is in a concavity of
      an object A1 not visible from an object A2 is considered between A1 and A2 for
      most definitions, which is counter intuitive. Also, none of the definitions deal
      with cases where one object is much more elongated than the other. Here, we
      propose definitions which are based on convexity, morphological operators, and
      separation tools, and a fuzzy notion of visibility. They correspond to the main
      intuitive exceptions of the relation. We distinguish between cases where objects
      have similar spatial extensions and cases where one object is much more extended
      than the other. Extensions to cases where objects, themselves, are fuzzy and to
      three-dimensional space are proposed as well. The original work proposed in this
      paper covers the main classes of situations and overcomes the limits of existing
      approaches, particularly concerning nonvisible concavities and extended objects.
      Moreover, the definitions capture the intrinsic imprecision attached to this
      relation. The main proposed definitions are illustrated on real data from medical
      images.

PMID- 16602593
TI  - Ratio-based lengths of intervals to improve fuzzy time series forecasting.
AB  - The objective of this study is to explore ways of determining the useful lengths
      of intervals in fuzzy time series. It is suggested that ratios, instead of equal
      lengths of intervals, can more properly represent the intervals among
      observations. Ratio-based lengths of intervals are, therefore, proposed to
      improve fuzzy time series forecasting. Algebraic growth data, such as enrollments
      and the stock index, and exponential growth data, such as inventory demand, are
      chosen as the forecasting targets, before forecasting based on the various
      lengths of intervals is performed. Furthermore, sensitivity analyses are also
      carried out for various percentiles. The ratio-based lengths of intervals are
      found to outperform the effective lengths of intervals, as well as the arbitrary
      ones in regard to the different statistical measures. The empirical analysis
      suggests that the ratio-based lengths of intervals can also be used to improve
      fuzzy time series forecasting.

PMID- 16602594
TI  - Improving signal prediction performance of neural networks through
      multiresolution learning approach.
AB  - In this paper, we extend the original work on multiresolution learning for neural
      networks, and present new developments on the multiresolution learning paradigm.
      The contributions of this paper include: (1) proposing a new concept and method
      of adjustable neural activation functions in multiresolution learning to improve
      neural network learning efficacy and generalization performance for signal
      predictions; (2) providing new insightful explanations for the multiresolution
      learning paradigm from a multiresolution optimization perspective; (3) exploring
      underlying ideas why the multiresolution learning scheme associated with
      adjustable activation functions would be more appropriate for the multiresolution
      learning paradigm; and (4) providing rigorous validations to evaluate the
      multiresolution learning paradigm with adjustable activation functions and
      comparing it with the schemes of multiresolution learning with fixed activation
      functions and traditional learning. This paper presents systematically new
      analytical and experimental results on the multiresolution learning approach for
      training an individual neural network model, demonstrates our integral solution
      on neural network learning efficacy, and illustrates the significant improvements
      on neural networks' generalization performance and robustness for nonlinear
      signal predictions.

PMID- 16602595
TI  - Training of a leaning agent for navigation--inspired by brain-machine interface.
AB  - The design clue for the remote control of a mobile robot is inspired by the
      Talwar's brain-machine interface technology for remotely training and controlling
      rats. Our biologically inspired autonomous robot control consciousness-based
      architecture (CBA) is used for the remote control of a robot as a substitute for
      a rat. CBA is a developmental hierarchy model of the relationship between
      consciousness and behavior, including a training algorithm. This training
      algorithm computes a shortcut path to a goal using a cognitive map created based
      on behavior obstructions during a single successful trial. However, failures in
      reaching the goal due to errors of the vision and dead reckoning sensors require
      human intervention to improve autonomous navigation. A human operator remotely
      intervenes in autonomous behaviors in two ways: low-level intervention in
      reflexive actions and high-level ones in the cognitive map. Experiments are
      conducted to test CBA functions for intervention with a joystick for a Khepera
      robot navigating from the center of a square obstacle with an open side toward a
      goal. Their statistical results show that both human interventions, especially
      high-level ones, are effective in drastically improving the success rate of
      autonomous detours.

PMID- 16602596
TI  - A versatile segmentation procedure.
AB  - In this paper, a new method for the segmentation of natural images is proposed.
      Original images g(x, y) are first regularized by using a self-adaptive
      implementation of the Mumford-Shah functional so that the two parameters alpha
      and gamma controlling the smoothness and fidelity, automatically adapt to the
      local scale and contrast of g(x, y). From the regularized image u(x, y) which is
      piecewise smooth, it is possible to obtain a piecewise constant image sN(x, y)
      representing a segmentation of the original image g(x, y). Indeed, sN(X, y) is
      the union of N closed regions, having a constant grey level, preserving thin bars
      and trihedral junctions present in the original image g(x, y). If the number N of
      closed regions is too high, closed regions can be merged by minimizing a
      functional which depends on a parameter n. When n is set equal to 1, a coarse
      segmentation is obtained with a few tens of distinct regions. With larger values
      of n, finer segmentations are obtained with about a hundred distinct regions.
      Therefore, by selecting the value of n it is possible to obtain segmentations at
      different resolutions. The proposed method for image segmentation was evaluated
      in two cases where a ground truth segmentation is available. The proposed
      procedure for image segmentation is rather versatile and depends on only one
      parameter n and seems suitable for higher level processing, such as
      categorization, recognition, and scene understanding.

PMID- 16602597
TI  - Kinematic analysis of a flexible six-DOF parallel mechanism.
AB  - In this paper, a new type of six-degrees of freedom (DOF) flexible parallel
      mechanism (FPM) is presented. This type of parallel mechanism possesses several
      favorable properties: (1) its number of DOFs is independent of the number of
      serial chains which make up the mechanism; (2) it has no kinematical
      singularities; (3) it is designed to move on rails, and therefore its workspace
      is much larger than that of a conventional parallel manipulator; and (4) without
      changing the number of DOFs and the kinematics of the mechanisms, the number of
      the serial chains can be reconfigured according to the needs of the tasks. These
      properties make the mechanism very preferable in practice, especially for such
      tasks as joining huge ship blocks, in which the manipulated objects vary
      dramatically both in weights and dimensions. Furthermore, the mechanism can be
      used as either a fully actuated system or an underactuated system. In the fully
      actuated case, the mechanism has six DOF motion capabilities and manipulation
      capabilities. However, in the underactuated case, the mechanism still has six DOF
      motion capabilities, but it has only five DOF manipulation capabilities. In this
      paper, both the inverse and forward kinematics are studied and expressed in a
      closed form. The workspace and singularity analysis of the mechanism are also
      presented. An example is presented to illustrate how to calculate the kinematics
      of the mechanism in both fully-actuated and underactuated cases. Finally, an
      application of such a mechanism to manufacturing industry is introduced.

PMID- 16602598
TI  - Segmentation of psoriasis vulgaris images using multiresolution-based orthogonal
      subspace techniques.
AB  - In this paper, a method is proposed for the segmentation of color images using a
      multiresolution-based signature subspace classifier (MSSC) with application to
      psoriasis images. The essential techniques consist of feature extraction and
      image segmentation (classification) methods. In this approach, the fuzzy texture
      spectrum and the two-dimensional fuzzy color histogram in the hue-saturation
      space are first adopted as the feature vector to locate homogeneous regions in
      the image. Then these regions are used to compute the signature matrices for the
      orthogonal subspace classifier to obtain a more accurate segmentation. To reduce
      the computational requirement, the MSSC has been developed. In the experiments,
      the method is quantitatively evaluated by using a similarity function and
      compared with the well-known LS-SVM method. The results show that the proposed
      algorithm can effectively segment psoriasis images. The proposed approach can
      also be applied to general color texture segmentation applications.

PMID- 16602599
TI  - Robust speaker's location detection in a vehicle environment using GMM models.
AB  - Abstract-Human-computer interaction (HCI) using speech communication is becoming
      increasingly important, especially in driving where safety is the primary
      concern. Knowing the speaker's location (i.e., speaker localization) not only
      improves the enhancement results of a corrupted signal, but also provides
      assistance to speaker identification. Since conventional speech localization
      algorithms suffer from the uncertainties of environmental complexity and noise,
      as well as from the microphone mismatch problem, they are frequently not robust
      in practice. Without a high reliability, the acceptance of speech-based HCI would
      never be realized. This work presents a novel speaker's location detection method
      and demonstrates high accuracy within a vehicle cabinet using a single linear
      microphone array. The proposed approach utilize Gaussian mixture models (GMM) to
      model the distributions of the phase differences among the microphones caused by
      the complex characteristic of room acoustic and microphone mismatch. The model
      can be applied both in near-field and far-field situations in a noisy
      environment. The individual Gaussian component of a GMM represents some general
      location-dependent but content and speaker-independent phase difference
      distributions. Moreover, the scheme performs well not only in nonline-of-sight
      cases, but also when the speakers are aligned toward the microphone array but at
      difference distances from it. This strong performance can be achieved by
      exploiting the fact that the phase difference distributions at different
      locations are distinguishable in the environment of a car. The experimental
      results also show that the proposed method outperforms the conventional multiple
      signal classification method (MUSIC) technique at various SNRs.

PMID- 16602600
TI  - Coarse-to-Fine vision-based localization by indexing scale-invariant features.
AB  - This paper presents a novel coarse-to-fine global localization approach inspired
      by object recognition and text retrieval techniques. Harris-Laplace interest
      points characterized by scale-invariant transformation feature descriptors are
      used as natural landmarks. They are indexed into two databases: a location vector
      space model (LVSM) and a location database. The localization process consists of
      two stages: coarse localization and fine localization. Coarse localization from
      the LVSM is fast, but not accurate enough, whereas localization from the location
      database using a voting algorithm is relatively slow, but more accurate. The
      integration of coarse and fine stages makes fast and reliable localization
      possible. If necessary, the localization result can be verified by epipolar
      geometry between the representative view in the database and the view to be
      localized. In addition, the localization system recovers the position of the
      camera by essential matrix decomposition. The localization system has been tested
      in indoor and outdoor environments. The results show that our approach is
      efficient and reliable.

PMID- 16602601
TI  - The balance between initial training and lifelong adaptation in evolving robot
      controllers.
AB  - A central aim of robotics research is to design robots that can perform in the
      real world; a real world that is often highly changeable in nature. An important
      challenge for researchers is therefore to produce robots that can improve their
      performance when the environment is stable, and adapt when the environment
      changes. This paper reports on experiments which show how evolutionary methods
      can provide lifelong adaptation for robots, and how this evolutionary process was
      embodied on the robot itself. A unique combination of training and lifelong
      adaptation are used, and this paper highlights the importance of training to this
      approach.

PMID- 16602602
TI  - Dynamics of facial expression: recognition of facial actions and their temporal
      segments from face profile image sequences.
AB  - Automatic analysis of human facial expression is a challenging problem with many
      applications. Most of the existing automated systems for facial expression
      analysis attempt to recognize a few prototypic emotional expressions, such as
      anger and happiness. Instead of representing another approach to machine analysis
      of prototypic facial expressions of emotion, the method presented in this paper
      attempts to handle a large range of human facial behavior by recognizing facial
      muscle actions that produce expressions. Virtually all of the existing vision
      systems for facial muscle action detection deal only with frontal-view face
      images and cannot handle temporal dynamics of facial actions. In this paper, we
      present a system for automatic recognition of facial action units (AUs) and their
      temporal models from long, profile-view face image sequences. We exploit particle
      filtering to track 15 facial points in an input face-profile sequence, and we
      introduce facial-action-dynamics recognition from continuous video input using
      temporal rules. The algorithm performs both automatic segmentation of an input
      video into facial expressions pictured and recognition of temporal segments
      (i.e., onset, apex, offset) of 27 AUs occurring alone or in a combination in the
      input face-profile video. A recognition rate of 87% is achieved.

PMID- 16602603
TI  - H(infinity) output tracking control for nonlinear systems via T-S fuzzy model
      approach.
AB  - This paper studies the problem of H(infinity) output tracking control for
      nonlinear time-delay systems using Takagi-Sugeno (T-S) fuzzy model approach. An
      LMI-based design method is proposed for achieving the output tracking purpose.
      Illustrative examples are given to show the effectiveness of the present results.

PMID- 16602604
TI  - Illumination compensation and normalization for robust face recognition using
      discrete cosine transform in logarithm domain.
AB  - This paper presents a novel illumination normalization approach for face
      recognition under varying lighting conditions. In the proposed approach, a
      discrete cosine transform (DCT) is employed to compensate for illumination
      variations in the logarithm domain. Since illumination variations mainly lie in
      the low-frequency band, an appropriate number of DCT coefficients are truncated
      to minimize variations under different lighting conditions. Experimental results
      on the Yale B database and CMU PIE database show that the proposed approach
      improves the performance significantly for the face images with large
      illumination variations. Moreover, the advantage of our approach is that it does
      not require any modeling steps and can be easily implemented in a real-time face
      recognition system.

PMID- 16602605
TI  - Active and dynamic information fusion for multisensor systems with dynamic
      Bayesian networks.
AB  - Many information fusion applications are often characterized by a high degree of
      complexity because: (1) data are often acquired from sensors of different
      modalities and with different degrees of uncertainty; (2) decisions must be made
      efficiently; and (3) the world situation evolves over time. To address these
      issues, we propose an information fusion framework based on dynamic Bayesian
      networks to provide active, dynamic, purposive and sufficing information fusion
      in order to arrive at a reliable conclusion with reasonable time and limited
      resources. The proposed framework is suited to applications where the decision
      must be made efficiently from dynamically available information of diverse and
      disparate sources.

PMID- 16602606
TI  - Neighborhood detection using mutual information for the identification of
      cellular automata.
AB  - Extracting the rules from spatio-temporal patterns generated by the evolution of
      cellular automata (CA) usually requires a priori information about the observed
      system, but in many applications little information will be known about the
      pattern. This paper introduces a new neighborhood detection algorithm which can
      determine the range of the neighborhood without any knowledge of the system by
      introducing a criterion based on mutual information (and an indication of over
      estimation). A coarse-to-fine identification routine is then proposed to
      determine the CA rule from the observed pattern. Examples, including data from a
      real experiment, are employed to evaluate the new algorithm.

PMID- 16602607
TI  - Nails and numbers.

PMID- 16602608
TI  - Cell phones don't cause tumors. From the United Kingdom Institute of Cancer
      Research.

PMID- 16602609
TI  - The medicinal leech.

PMID- 16602610
TI  - Fatal pulmonary Mycobacterium abscessus infection in a patient using etanercept.
AB  - A case of fatal pulmonary Mycobacterium abscessus infection in a 56-year-old man
      is reported. The patient had a longstanding history of seropositive, nodular
      rheumatoid arthritis with severe joint manifestations that had been treated with
      a regimen of prednisone, leflunomide, and etanercept. He presented to our
      facility with complaint of productive cough, persistent fevers, pleuritic chest
      discomfort, and dyspnea at rest. The patient was admitted to hospital, placed in
      isolation, a left-sided chest tube was inserted (left pneumothorax identified),
      and sputum acid-fast bacteria stains and cultures were obtained. Fluorochrome
      stains demonstrated numerous acid-fast bacteria, and M. abscessus was recovered
      from the culture media. He was treated with a regimen of amikacin, cefoxitin, and
      clarithromycin. He initially responded well, and was discharged home with this
      regimen. He remained afebrile with decreased cough and sputum production until 15
      days after discharge when he was again admitted to hospital, with acute onset
      dyspnea and right-sided chest discomfort (right pneumothorax identified). He
      ultimately expired, due to overwhelming pulmonary infection, 20 days after
      readmission to hospital. Autopsy revealed acid fast bacilli in the setting of
      numerous, bilateral, necrotic, granulomatous, cavitary pulmonary lesions. Based
      on its mechanism of action, we propose an association between the use of
      etanercept, a tumor necrosis factor alpha (TNF-alpha) inhibitor, and this case of
      fatal pulmonary mycobacterial infection. We recommend that physicians exercise
      cautious clinical judgment when initiating etanercept therapy in persons with
      underlying lung disease, especially in communities in which mycobacterial
      organisms are highly prevalent. We also advise physicians to maintain a high
      level of vigilance for late onset granulomatous infection in persons using
      etanercept.

PMID- 16602611
TI  - Severe vitamin D deficiency in Hawai'i: a case report.
AB  - Severe vitamin D deficiency would appear unlikely to occur in Hawai'i, which has
      abundant year-round sun exposure. This case report of a woman with no obvious
      risk factors for vitamin D deficiency who was found to have severe vitamin D
      deficiency and coexisting primary hyperparathyroidism should alert health care
      providers to be more aware of vitamin D deficiency in Hawai'i.

PMID- 16602612
TI  - An unusual abdominal tumor--leiomyosarcoma of the mesentery: a case report.
AB  - We report the case of an 82-year-old woman who presented with an ill-defined mass
      and tenderness in the right lower quadrant of the abdomen. On computerized
      tomography scan, she had an irregular large bosselated mass of the mesentery
      located medial to the cecum and associated with multiple loops of small
      intestine. Preoperative differential diagnoses included leiomyosarcoma, lymphoma
      and gastrointestinal stromal tumor. The mesenteric mass was resected and
      identified as a leiomyosarcoma. This patient's tumor is typical of a mesenteric
      leiomyosarcoma and recurred with hepatic metastases two years after its initial
      removal. Such tumors usually do not become symptomatic until late in the course
      of disease, often after distant metastases have occurred. Mesenteric
      leiomyosarcomas are rare and have a reported incidence of 1: 350,000.

PMID- 16602613
TI  - Case report: a 17-year-old female with headache and fever. Murine typhus.

PMID- 16602614
TI  - Department of Pediatrics at the John A. Burns School of Medicine (JABSOM) 2004
      2005 update.

PMID- 16602615
TI  - Risk factors for pancreatic cancer in the Hawai'i-Los Angeles Multiethnic Cohort
      Study.

PMID- 16602616
TI  - Securing our future one task at a time.

PMID- 16602617
TI  - Wind beneath my wings.

PMID- 16602618
TI  - The benefits of mentoring.

PMID- 16602619
TI  - Kaizen & the art of mentoring.

PMID- 16602621
TI  - Non-work related injuries and leaves of absence.

PMID- 16602620
TI  - A mentor's legacy in local dentistry.

PMID- 16602622
TI  - Nostalgia ... December 7, 1941.

PMID- 16602623
TI  - New insights in antigen processing and epitope selection: development of novel
      immunotherapeutic strategies for cancer, autoimmunity and infectious diseases.
AB  - Current evidence suggests that MHC class II-restricted CD4+ T-cells play a
      crucial role in orchestrating host immune responses against cancer as well as
      autoimmune and infectious diseases. Antigens must be processed within endosomal
      and lysosomal compartments of antigen presenting cells (APC) before binding to
      MHC class II molecules for display to T-cells. Only a limited number of processed
      peptides termed immunodominant are selected for display by MHC class II molecules
      and prove capable of inducing strong T-cell responses. Thus processing reactions
      within APC are of central importance for the development of effective vaccines as
      they modulate the number of peptide: class II complexes by enhancing or
      disrupting epitope formation and display. Studies suggest that there are
      substantial gaps in our knowledge of how antigen processing and presentation by
      APC regulates epitope selection and immunodominance in disease situations. Here
      we describe new insights in antigen processing and epitope selection with
      relevance to immunotherapeutic strategies for cancer, autoimmunity and infectious
      diseases.

PMID- 16602624
TI  - Cationization of monoclonal antibodies: another step towards the "magic bullet"?
AB  - Monoclonal antibodies have represented since the beginning a potent means to
      identify specific antigen. The engineering of monoclonal antibodies has created a
      new generation of pharmaceuticals with the desired pharmacokinetics and
      biodistribution properties. Optimum tumor targeting can be achieved using
      engineering constructs that provide high antigen affinity and specificity,
      effective tumor penetration with acceptable doses to normal tissue. Cationization
      is a technique to modify antibodies in such a way as to develop improved
      radiopharmaceuticals. A brief review of how monoclonal antibodies can be modified
      to improve their applicability for target therapies and diagnosis is here
      presented.

PMID- 16602625
TI  - Transcriptional upregulation of the human MRP2 gene expression by
      serine/threonine protein kinase inhibitors.
AB  - Transcriptional regulation by cellular signalling pathways of multidrug
      resistance proteins that pump anticancer drugs out of cells is one of key issues
      in the development of the multidrug resistance phenotype. In our study, we have
      used the reporter gene approach as well as determination of mRNA levels in two
      cancer cell lines of human origin, MCF-7 and A549, to study the regulation of
      multidrug resistance proteins 2 and 3 (MRP2 AND MRP3) by serine/threonine protein
      kinases. Since a prototypic PKC inducer, PMA, caused a marked upregulation of
      transcription from both human MRP2 and MRP3 promoters, a role for PKC isoforms in
      positive control of expression of these proteins could be postulated.
      Interestingly, broad-spectrum serine-threonine protein kinase inhibitors which
      also inhibit PKC, staurosporine and H-7, stimulated expression from the MRP2
      promoter instead of inhibiting it. This effect was not seen for MRP3. MRP2
      induction by staurosporine and H-7 was shown to have phenotypic consequences in
      whole cells, rendering them more resistant to etoposide and increasing their
      ability to export calcein through the plasma membrane. These results point to the
      involvement of serine/threonine protein kinases in negative regulation of the
      human MRP2 gene and to the necessity of testing novel anti-cancer drugs acting as
      protein kinase inhibitors with regard to their potential ability to induce
      multidrug resistance.

PMID- 16602626
TI  - Toxicity of xanthine oxidoreductase to malignant B lymphocytes.
AB  - Reactive oxygen species (ROS) generated by xanthine oxidoreductase (XOR) were
      toxic to B lymphoma-derived Raji cells (positive for 8A monoclonal antibody,
      mAb). The sensitivity of these malignant cells to the hypoxanthine/XOR system was
      higher than that observed in peripheral human lymphocytes. The understanding of
      the mechanisms of cytotoxicity induced by XOR-produced ROS is essential in view
      of a possible clinical application. Cell death mostly had the feature of
      apoptosis and post-apoptotic necrosis and depended on the activity of XOR.
      Catalase, but not superoxide dismutase, protected cells from the toxicity of XOR,
      thus indicating that cell damage depended on the production of hydrogen peroxide.
      The toxicity of ROS was selectively targeted to malignant Raji cells by antibody
      XOR conjugation, either directly, with an 8A-XOR conjugate, or indirectly, with
      an 8A mAb plus an anti-mouse IgG-XOR. Both direct and indirect immunotoxins
      induced apoptotic death to target cells in a dose-dependent manner. These
      conjugates showed no aspecific cytotoxicity in conditions very similar to the ex
      vivo treatment of cell suspension for bone marrow transplantation. Moreover, the
      prevalence of apoptotic death over necrosis may reduce the in vivo inflammatory
      response and its local and systemic consequences, thus becoming relevant in the
      construction of immunotoxins with therapeutic potential.

PMID- 16602627
TI  - Rat peritoneal mast cells release regulated upon activation normal T cell
      expressed and secreted (RANTES) after TNF-alpha activation.
AB  - Chemokines are a family consisting of at least ten distinct novel 8-10 kD
      cytokines. The cysteine-cysteine (C-C) chemokines are chemoattractant and
      activators for monocytes, T cells and mast cells. RANTES is the prototype of the
      C-C chemokine subfamily, purified from different sources with chemoattractant and
      activator properties. In this study we found that supernatants derived from TNF
      alpha (scalar concentrations)-activated rat peritoneal mast cell cultures (5 x
      10(5)/mL), incubated overnight, produced high levels of RANTES. This data
      describes an additional mode of generation of RANTES. Moreover, RANTES mRNA was
      not significantly produced in untreated cells, while it was dramatically
      increased by calcium ionophore A23187, LPS and TNF-alpha compared with the
      controls. These results underscore the importance of the presence of mast cells
      for the production of RANTES in the inflammatory process and contribute to an
      understanding of the mechanism by which RANTES profoundly affects inflammatory
      responses in vivo.

PMID- 16602628
TI  - 60-kDa heat shock protein of Chlamydia pneumoniae is a target of T-cell immune
      response.
AB  - Inflammatory processes contribute to the pathogenesis and complications of
      atherosclerosis and coronary heart disease (CHD). Several findings indicate that
      chlamydial heat shock proteins (HSP) may represent a particularly strong
      antigenic stimulus, able to induce specific humoral (Ab) and T-cell-mediated
      immune responses (CMI) linking infection by Chlamydia pneumoniae (CP) to immuno
      pathological sequelae such as atherosclerosis and CHD. We have here evaluated the
      ability of chlamydial recombinant (r) HSP60 and rHSP10 to induce specific immune
      responses in human peripheral blood lymphocytes and in murine models. rHSP60, but
      not rHSP10, was shown to induce proliferation and Interferon-gamma secretion in
      lymphocytes of randomly selected blood donors, as well as to generate and detect
      delayed-type hypersensitivity response in HSP60-vaccinated mice. Overall, the
      present study provides new hints to evaluate a previous exposition to CP using
      rHSP60 in humans. Thus the evaluation of specific HSP60 CMI response in healthy
      subject could be useful to monitor the reactivity to Chlamydia pneumoniae
      possibly providing a link to CHD pathologies.

PMID- 16602629
TI  - Cortisol response to an acute injection of IL-2 in healthy subjects and cancer
      patients: a first immunoneuroendocrine standardized clinical test to explore the
      interactions between immune and neuroendocrine systems.
AB  - Preliminary clinical studies would suggest that the immune alterations
      characterizing severe human illnesses, such as autoimmune diseases and cancer
      itself, may depend at least in part on an anomalous psychoneuroendocrine
      regulation of the immunity. Unfortunately, at present the psychoneuroimmune
      interactions may be clinically investigated only by separately analyzing the
      neuroendocrine and the immune systems, since there is no standardized clinical
      test capable of detecting the physiological response of the endocrine secretion
      to an immune stimulation. One of the main endocrine functions influenced by the
      immune activation is the hypothalamic-pituitary-adrenal axis. In fact, several
      cytokines have appeared to stimulate cortisol secretion by acting at a central
      site. On this basis, a study was planned to evaluate cortisol response to an
      acute IL-2 injection in healthy subjects and metastatic cancer patients, in an
      attempt to standardize a clinical neuroendocrinoimmune test capable of
      documenting possible alterations of the link between neuroendocrine and immune
      systems. The study included 10 healthy subjects as a control group and 10 cancer
      patients with metastatic disease. Control subjects were evaluated in basal
      conditions to determine the physiological circadian rhythm of cortisol, and after
      the subcutaneous (SC) injection of IL-2 (3 and 9 million IU). IL-2 at 3 million
      IU stimulated cortisol release in all healthy controls and in none of the cancer
      patients. IL-2 at 9 million IU induced a significant increase in cortisol mean
      levels in cancer patients, whose values, however, were still significantly lower
      with respect to those seen in controls in response to IL-2 at 3 million IU. No
      important IL-2 related side-effect occurred. This study shows that an acute SC
      injection of low-dose IL-2 with a following evaluation of cortisol secretion may
      constitute a first standardized immunoendocrine test, capable of exploring the
      status of the physiological link between neuroendocrine and immune systems, and
      of documenting the existence of important alterations in human diseases related
      to an immune dysfunction, such as advanced cancer, which has appeared to be
      characterized by a hyposensitivity of the hypothalamic-pituitary-adrenal axis to
      an acute cytokine administration.

PMID- 16602630
TI  - CD38 as a target of IB4 mAb carrying saporin-S6: design of an immunotoxin for ex
      vivo depletion of hematological CD38+ neoplasia.
AB  - An anti-CD38 mAb (IB4) coupled to saporin-S6, a type 1 ribosome-inactivating
      protein (RIP), was designed for ex vivo or loco-regional therapeutical
      applications in myeloma and lymphoma. The ability of this immunotoxin to
      eliminate CD38+ cells was studied in vitro on selected CD38+ human cell lines
      (Raji, HBL6, L540 and CEM) and on CD38+ neoplastic cells from a Non Hodgkin
      Lymphoma (NHL) patient. HBL6, Raji and L540 cells resulted very sensitive to the
      IB4/saporin-S6 conjugate, concentrations as low as 100 pM of the immunotoxin
      completely inhibited protein synthesis. CD38+ neoplastic cells from the NHL
      patient were completely eliminated after treatment with immunotoxin at 10 nM
      concentration. CFU-c rescue by bone marrow precursors was maintained after
      exposure to the immunotoxin. These results indicate that IB4/saporin-S6 is
      endowed with strong and specific cytotoxic effects on selected CD38+ tumor cells
      lineages. Consequently, it is reasonable to propose a clinical use of the
      IB4/saporin-S6 for ex vivo purging of unwanted cells (e.g. depletion of
      contaminating neoplastic cells in aphereses obtained from G-CSF-treated patients)
      or for loco-regional therapies of CD38+ tumors.

PMID- 16602631
TI  - Radiotherapy-induced lymphocytopenia: changes in total lymphocyte count and in
      lymphocyte subpopulations under pelvic irradiation in gynecologic neoplasms.
AB  - Lymphocytopenia is one of the most negative biological prognostic factors in
      cancer patients. Lymphocytopenia may depend on tumor progression, or on various
      anticancer therapies. In particular, radiotherapy (RT) may induce direct
      lymphocyte damage. The present study was carried out to evaluate the influence of
      pelvic irradiation on lymphocyte number and lymphocyte subpopulations in patients
      with gynecologic tumors. The study included 40 patients affected by locally
      limited or advanced uterine tumors, who underwent pelvic irradiation for a total
      dose of 50.4 Gy. RT induced a significant decline in total lymphocyte number,
      with values lower than 500/mm3 in 29/40 (73%) patients and with a mean decrease
      of 71 +/- 4%. In the same way, T lymphocyte, CD4, CD8 and NK cell mean numbers
      significantly decreased under RT. The decline in NK and CD8 cells was limited to
      the first 2-3 weeks of irradiation, whereas that involving T lymphocytes and CD4
      cells was progressive and persistent until the end of RT. Finally, the decline in
      total lymphocyte number was significantly greater in patients who had no tumor
      regression in response to RT. This study confirms that pelvic RT may induce
      severe lymphocytopenia which could negatively influence the efficacy of RT
      itself.

PMID- 16602632
TI  - Monitoring of peripheral blood cytotoxic T-cells under fluvastatin treatment in
      renal transplant recipients.
AB  - Flow cytometric T-cell analysis is capable of adding valuable information for
      balancing immunosuppression in transplant recipients as it can take into account
      individual effects of immunosuppressive drugs on each patient as well as effects
      of other drugs which may modify the overall immunosuppression. Studies suggest
      that HMG-CoA-reductase-inhibitors (statins) reduce the frequency of organ
      rejection, although the precise mechanism of this effect is unknown. We therefore
      evaluated the effect of fluvastatin on size and activation of T-cell
      subpopulations and NK-cell activity in renal transplant recipients. At baseline,
      the population size of activated (HLA-DR+) T-cells was negatively correlated to
      serum HDL cholesterol suggesting an increased T-cell activation at low HDL
      levels. Fluvastatin treatment of a hypercholesterolemic group of patients for two
      months significantly decreased the LDL cholesterol. A longitudinal analysis
      revealed a relative increase in non-MHC restricted cytotoxic T-cells (CD3+/CD16+
      or CD56+) over time which was significantly attenuated in fluvastatin treated
      patients but not in normocholesterolemic controls. Moreover, a relative decrease
      of activated MHC class I-restricted cytotoxic CD8+ T-cells was only observed upon
      fluvastatin treatment. NK-cell number and activity did not differ between groups.
      In summary, fluvastatin treatment of hypercholesterolemic renal transplant
      recipients is associated with a specific modulation of T-cells exerting cytotoxic
      effector functions.

PMID- 16602634
TI  - Enumeration of activated sludge bacteria in a wastewater treatment plant.

PMID- 16602633
TI  - Panleucogating as an accurate and affordable flow cytometric protocol to analyse
      lymphocyte subsets among HIV-positive patients on HAART treatment in Mozambique.
AB  - In Africa tens of millions of people are HIV+. Prevention alone is not effective,
      and needs to be coupled with anti-retroviral treatment (HAART). Laboratory tests
      as CD4+ T cell count are fundamental tools in HIV disease monitoring, but they
      require costly equipment, reagents and specialised manpower. The goal of this
      study was to minimise and optimise the reagents needed for a reliable routine
      CD4+ cell count in a resource-poor setting (Mozambique). Panleucogating protocol
      (PLG), requires two antibodies only, CD45 and CD4, or three if CD8 is requested
      for special clinical reasons. PLG was compared with the current protocol used in
      two Mozambique hospitals, based on FSC/SSC gating and CD3/CD4/CD8 staining. 189
      samples from HIV+ patients, included in the Community of Sant'Egidio's DREAM
      program and on HAART were processed with both protocols. The overall correlation
      of the lymphocyte subsets measurements was satisfactory, with r2 always >0.96.
      The Bland-Altman analysis of CD4+ cell count showed a negative bias when CD4+
      cells were <15%, due to the imprecise FSC/SSC gating used previously. When CD4+
      cells were >15% the negative bias tended to zero, further confirming the better
      quality of the PLG gating strategy. Two- or three color PLG protocol, in double
      platform, currently seems the most accurate and affordable method to monitor CD4+
      lymphocytes and CD4/CD8 ratio by flow cytometry in resource-poor medical
      settings.

PMID- 16602635
TI  - Detection and quantification of endothelial progenitor cells by flow and laser
      scanning cytometry.

PMID- 16602636
TI  - Your first year as a nurse.

PMID- 16602637
TI  - A guide to NCLEX-RN success.

PMID- 16602638
TI  - Public health nursing: keeping America healthy.

PMID- 16602639
TI  - Working with the USPHS: an adventure waiting to happen.

PMID- 16602640
TI  - Q&A with a periOperative nurse.

PMID- 16602641
TI  - Have you considered a career as a researcher and scholar in nursing.

PMID- 16602642
TI  - Life, death, and lessons learned in Tanzania.

PMID- 16602643
TI  - Solving the crisis of nursing diversity: can we learn from the army?

PMID- 16602644
TI  - Accreditation of foreign dental schools.

PMID- 16602645
TI  - What exactly constitutes fraud?

PMID- 16602646
TI  - The problem with holiday staff parties.

PMID- 16602647
TI  - "Moments of truth": how does your practice stack up?

PMID- 16602649
TI  - Use of a one-stage narrow-diameter implant to replace incisors.

PMID- 16602651
TI  - [More elderly people, less sick people].

PMID- 16602654
TI  - [Does the night follow good days?].

PMID- 16602655
TI  - [Night work and health repercussions].

PMID- 16602656
TI  - [Night and evening care].

PMID- 16602657
TI  - [Vigilance is the heart of the nursing profession].

PMID- 16602658
TI  - [Profile of the night nursing job in an extended care service].

PMID- 16602659
TI  - [Floating night aide, risky bet or possible development?].

PMID- 16602660
TI  - [The Foundation of France supports the floating night aide program].

PMID- 16602661
TI  - [Specifics of night care in the geriatric institution].

PMID- 16602662
TI  - [How to manage insomnia in the elderly?].

PMID- 16602663
TI  - [Communicating with Alzheimer patients].

PMID- 16602664
TI  - [Guidelines for mouth care].

PMID- 16602665
TI  - [Taking care in geriatrics].

PMID- 16602666
TI  - [Financing of geriatric care activities and specifics].

PMID- 16602667
TI  - [What is your diagnosis? The examination shows peripheral facial paresis].

PMID- 16602668
TI  - [Long-term treatment of patients with symptomatic gastroesophageal reflux disease
      comparing costs and efficacy over 6 months of treatment with Nexium On-Demand
      Treatment or Nexium continuous treatment. An open, randomised multi-center
      study].
AB  - This open, randomized study (ONE: On-demand Nexium Evaluation) compared the two
      long-term management options with esomeprazole 20 mg--continuous daily or on
      demand treatment--in endoscopically uninvestigated patients seeking primary care
      for symptoms suggestive of gastroesophageal reflux disease (GERD) who
      demonstrated complete relief of symptoms after four weeks of initial treatment
      with esomeprazole 40 mg. In total 1904 patients were randomized. During 26 weeks
      913 patients received continuous daily therapy with esomeprazole 20 mg, once
      daily, while 991 patients were treated with esomeprazole 20 mg on-demand. The
      continuous therapy offered slightly better relief of the symptom heartburn,
      however esomeprazole 20 mg taken on-demand was associated with lower direct
      medical costs. Esomeprazole was generally well tolerated.

PMID- 16602669
TI  - [Aphasia in stroke patients: frequency and significance].

PMID- 16602670
TI  - [Is the metabolic syndrome a new childhood disease?].
AB  - Overweight and obesity in children and adolescents have become a major public
      health problem in recent years throughout the world. The medical consequences of
      obesity may manifest as an increase in the prevalence of the metabolic syndrome
      in children and adolescents putting them at increased risk for future
      cardiovascular diseases. Obesity can cause insulin resistance and might disturb
      glucose homeostasis eventually leading to type 2 diabetes in susceptible
      patients. Insulin resistance is also involved in the pathogenesis of dyslipidemia
      in obese children characteristically presenting as hypertriglyceridemia and low
      HDL cholesterol. Even elevated blood pressure might be present in obese kids.
      Here we present a 12-year-old boy diagnosed with the metabolic syndrome. The
      diagnostic criteria of the metabolic syndrome in children and adolescents are
      discussed. Thoughts about pathophysiology and therapeutic options are offered.

PMID- 16602671
TI  - [More than muscle stiffness].
AB  - A four-month-old infant was hospitalized because of RSV bronchiolitis. Two days
      after presentation he developed rhabdomyolysis, most probably as a result of
      multiple factors (hyperthermia, hypovolemia/dehydration, hypernatremia, metabolic
      acidosis), followed by severe complications including acute renal failure,
      hepatic dysfunction and disseminated intravascular coagulation. Under sufficient
      fluid supply he recovered completely. In rhabdomyolysis clinical symptoms vary.
      Seldom, the classical trial of muscle pain, weakness, and dark urine is observed.
      Severe complications are hypovolemia, electrolyte disorders, a compartment
      syndrome, disseminated intravascular coagulation and acute renal failure, which
      causes death in 20% of the patients, although non-traumatic causes seem to have
      better outcome. The mainly therapeutic option is to correct the hypovolemia with
      sufficient fluid supply.

PMID- 16602672
TI  - [Sudden chest pain and shortness of breath in a young man].

PMID- 16602673
TI  - [Cardiomyopathy].

PMID- 16602674
TI  - History of hydrocephalus and its treatments.
AB  - Hydrocephalus has amazed and challenged clinicians throughout the history of
      medicine. In reviewing the treatment of hydrocephalus, the integral relationship
      between basic science and therapy is reaffirmed. As we embark into a new
      millennium, it is appropriate to reflect on the past studies of this disorder,
      review various attempted and currently used, and finally speculate on possible
      future directions in its treatment.

PMID- 16602675
TI  - The historical development of the pseudotumor concept.
AB  - The author outlines the history of the development of the pseudotumor concept,
      first specifically formulated by Nonne in 1904 but implicit in earlier
      descriptions. A scheme of periodization is applied, identifying otological,
      neurosurgical, neurological, and neuroophthalmological periods; he relates
      theoretical and practical developments in the understanding of the condition to
      the concerns of the dominant speciality involved in diagnosis and management. Key
      studies from each period are discussed in relation to the issues of mechanism,
      origin, nomenclature, diagnosis, and treatment. During the otological period,
      approaches to the condition were heavily influenced by its common association
      with middle ear infection, often with venous sinus involvement, and this led to
      the idea of disturbed cerebrospinal fluid dynamics as the cause. The advent of
      neuroradiological systems ushered in the neurosurgical period in which the
      significant but unfinished debate began: which intracranial compartment is
      primarily implicated in the intracranial hypertension? By the time of the
      neurological period cerebral edema was implicated as the cause, and this
      coincided with the availability of appropriate treatment methods and steroidal
      and diuretic agents. Toward the end of this period additional major advances in
      investigative methods again brought the issue of mechanism into contention,
      although a resolution was not to follow. The neuroophthalmological period is
      characterized by an increased awareness of the significance of visual loss and a
      return to one of the original methods of treatment. Finally, the possible
      significance of impaired cranial venous outflow, a thread running through all
      periods, is considered.

PMID- 16602676
TI  - Brief history of surgical timing: surgery for ruptured intracranial aneurysms.
AB  - The neurosurgical profession has taken a circuitous route to attain its current
      knowledge about timing for aneurysm surgery. While addressing the timing issue,
      neurosurgeons were beset by many pressures simultaneously. They were forced to
      justify not only optimal surgical techniques but the need for surgery at all in
      the treatment of ruptured aneurysms. The beliefs of surgeons with strong
      personalities, in addition to intuitive guesses, often served to guide surgery in
      the absence of scientific evidence. That any progress could be made against a
      background of desperately ill patients and frustrating early results is
      remarkable. The author briefly outlines the controversies and misdirection that
      accompanied this progress toward understanding surgical timing in the treatment
      of ruptured aneurysms.

PMID- 16602677
TI  - A brief history of aneurysm clips.
AB  - In this communication the authors outline the development of aneurysm clips from
      those originally used by Walter Dandy to those currently in use. The history is
      rich in contributions from neurosurgical pioneers and innovators. As a result,
      the modern neurosurgeon has a wide selection of biocompatible aneurysm clips with
      known closing pressure, of variable sizes and shapes, and a selection of clip
      applicators that do not obstruct the surgical field.

PMID- 16602678
TI  - Ibn Sina (Avicenna). Historical note.
AB  - Ibn Sina (often known by his last name in Latin, Avicenna; 980-1037 A.D.) was the
      most famous physician and philosopher of his time. His Canon of Medicine, one of
      the most famous books in the history of medicine, surveyed the entire medical
      knowledge available from ancient and Muslim sources and provided his own
      contributions. In this article the authors present a unique picture of the
      neurosurgical technique of Ibn Sina and briefly summarize his life and work.

PMID- 16602679
TI  - Irving S. Cooper and the early surgical management of movement disorders. Video
      history.
AB  - Irving S. Cooper was a pioneer in the field of functional neurosurgery. During
      his very productive and controversial career, he proposed the surgical treatment
      of Parkinson disease (PD) by ligating the anterior choroidal artery to control
      tremor and rigidity. Subsequently, he developed seminal techniques for
      chemopallidectomy and cryothalamectomy for PD. He also attempted to use
      electrical stimulation of the cerebellum or the thalamus to treat spasticity.
      Cooper continued his work on brain stimulation until his death in 1985. He made
      video recordings of nearly all of his patients during his tenure (1977-1985) at
      New York Medical College. Cooper's clinical video recordings were reviewed, and
      selected footage was compiled into a video history of Cooper's surgical
      management of various movement disorders. Included are pre-, post-, and some
      intraoperative recordings that Cooper made to document his treatment of patients
      with PD, tremor, Wilson disease, cerebral palsy, chorea, dystonia musculorum
      deformans, and some rarer entities.

PMID- 16602680
TI  - Epithelial proteomics in multiple organs and tissues: similarities and variations
      between cells, organs, and diseases.
AB  - Epithelial cells play an important role in physiological and pathophysiological
      situations, with organ-, tissue-, type-, and function-specific patterns. Proteome
      analysis has been used to study epithelial-origin diseases and identify novel
      prognostic, diagnostic, and therapeutic markers. The present review compares the
      variation of sample preparation for epithelial proteomic analysis, search
      similarities, and differences of epithelial proteomics between different cells,
      locations, and diseases. We focus on specificity of proteomic markers for
      epithelial-involved diseases. Proteomic alterations in epithelial cell lines were
      mapped to understand protein patterns, differentiation, oncogenesis, and
      pathogenesis of epithelial-origin diseases. Changes of proteomic patterns depend
      on different epithelial cell lines, challenges, and preparation. Epithelial
      protein profiles associated with intracellular locations and protein function.
      Epithelial proteomics has been greatly developed to link clinical questions,
      e.g., disease severity, biomarkers for disease diagnosis, and drug targets. There
      is an exciting and attractive start to link epithelial proteomics with histology
      of clinical samples. From the present review, we can find that most of disease
      associated investigation of epithelial proteomics has been focused on epithelial
      origin cancer. There is a significant gap of epithelial proteomics between acute
      and chronic organ injury, inflammation, and multiple organ dysfunction.
      Epithelial proteomics will provide powerful information on the relationships
      between biological molecules and disease mechanisms. Epithelial proteomics
      strategies and approaches should become more global, multidimensional, and
      systemic.

PMID- 16602681
TI  - Metabolic profiling of plasma from discordant schizophrenia twins: correlation
      between lipid signals and global functioning in female schizophrenia patients.
AB  - (1)H NMR spectroscopy-based metabonomic analysis was employed to investigate
      plasma samples from 21 pairs of monozygotic twins discordant for schizophrenia
      and 8 pairs of age-matched healthy twins in an effort to disentangle genetic and
      epigenetic components of schizophrenia. We identified alterations in the lipid
      profile of both affected and unaffected schizophrenia twins. Additionally, there
      is a close association of VLDL/LDL signals and Global Functioning Scores in
      female twins suffering from schizophrenia. Our results further support a link
      between metabolic disturbances and the etiopathology of schizophrenia.

PMID- 16602682
TI  - Improved identification of SUMO attachment sites using C-terminal SUMO mutants
      and tailored protease digestion strategies.
AB  - A growing number of biological processes have been found to be regulated by the
      covalent attachment of the ubiquitin-like protein SUMO to key cellular targets. A
      critical step in the process of analyzing the role of SUMO in regulating the
      activity of these proteins is the identification of the lysine residues that are
      targeted by this modification. Unfortunately, current methods aimed at mapping
      these attachment-sites are laborious and often ineffective. We report here the
      development of a platform that combines the use of different C-terminal SUMO
      mutants with different protease digestion strategies to enable the rapid and
      efficient identification of SUMO attachment sites. We successfully apply this
      approach to several model SUMO substrates as well as to a mixture of SUMO
      conjugates purified from Saccharomyces cerevisiae. Although we specifically
      employ this strategy for the identification of SUMO attachment sites in yeast,
      this general approach can easily be adapted to map the sites of conjugation for
      other ubiquitin-like proteins from a wide range of organisms.

PMID- 16602683
TI  - A chick retinal proteome database and differential retinal protein expressions
      during early ocular development.
AB  - Proteomics approach as a research tool has gained popularity in a growing number
      of basic and clinical researches. However, proteomic research has yet to gain
      significant momentum in eye research. Hence, we decided to build a retinal
      proteome database using postnatal retinal tissue from chick, a commonly used
      animal model in eye research. Employing 2-D gels with the coverage of 3-10 pH
      gradients, we were able to resolve hundreds of proteins from young chick retinae.
      Among them, 155 high abundant proteins were identified by Peptide Mass
      Fingerprinting (PMF) after the Matrix-Assisted Laser Desorption Ionization-Time
      of-Flight Mass Spectrometry (MALDI-TOF MS). These proteins were then classified
      according to their functions. Making use of the retinal database, we were able to
      identify several differentially expressed proteins that might be involved in
      early retinal development by comparing the 2-DE maps of chick retinal tissues (3,
      10, and 20 days after hatching). With the current proteomics approach, we not
      only documented the most abundant soluble proteins in the chick retinal tissue,
      but also demonstrated the dynamic protein expression changes during early ocular
      development. This represents one of the first steps in building a complete
      protein database in chick retinae which is applicable to the study of eye
      diseases from a few selected protein candidates to the whole proteome. Proteomic
      technology may provide a high throughput platform for advancing eye research in
      the feasible future.

PMID- 16602684
TI  - Detection and identification of protein isoforms using cluster analysis of MALDI
      MS mass spectra.
AB  - We describe an approach to screen large sets of MALDI-MS mass spectra for protein
      isoforms separated on two-dimensional electrophoresis gels. Mass spectra are
      matched against each other by utilizing extracted peak mass lists and
      hierarchical clustering. The output is presented as dendrograms in which protein
      isoforms cluster together. Clustering could be applied to mass spectra from
      different sample sets, dates, and instruments, revealed similarities between mass
      spectra, and was a useful tool to highlight peptide peaks of interest for further
      investigation. Shared peak masses in a cluster could be identified and were used
      to create novel peak mass lists suitable for protein identification using peptide
      mass fingerprinting. Complex mass spectra consisting of more than one protein
      were deconvoluted using information from other mass spectra in the same cluster.
      The number of peptide peaks shared between mass spectra in a cluster was
      typically found to be larger than the number of peaks that matched to calculated
      peak masses in databases, thus modified peaks are probably among the shared
      peptides. Clustering increased the number of peaks associated with a given
      protein.

PMID- 16602685
TI  - Probing cysteine reactivity in proteins by mass spectrometric EC-tagging.
AB  - The on-line electrochemical tagging (EC-tagging) of cysteine residues in proteins
      during mass spectrometry is studied to probe the cysteine environment.
      Benzoquinone probes electrogenerated at a microspray electrode react with the
      thiol functions of the proteins within a microchannel and the products are
      analyzed by mass spectrometry. The fundamentals of the technique are discussed,
      with a focus on the kinetic aspects. The EC-tagging efficiency of the cysteine
      residues in proteins is used to probe their environment. Experiments with
      unmodified proteins and their chemically reduced forms highlight the strong
      effect of the cysteine site reactivity on the tagging efficiencies. This study
      highlights relevant parameters for such on-line electrochemical derivatization/MS
      detection strategies.

PMID- 16602686
TI  - Fast and accurate method for identifying high-quality protein-interaction modules
      by clique merging and its application to yeast.
AB  - Molecular networks in cells are organized into functional modules, where genes in
      the same module interact densely with each other and participate in the same
      biological process. Thus, identification of modules from molecular networks is an
      important step toward a better understanding of how cells function through the
      molecular networks. Here, we propose a simple, automatic method, called MC(2), to
      identify functional modules by enumerating and merging cliques in the protein
      interaction data from large-scale experiments. Application of MC(2) to the S.
      cerevisiae protein-interaction data produces 84 modules, whose sizes range from 4
      to 69 genes. The majority of the discovered modules are significantly enriched
      with a highly specific process term (at least 4 levels below root) and a specific
      cellular component in Gene Ontology (GO) tree. The average fraction of genes with
      the most enriched GO term for all modules is 82% for specific biological
      processes and 78% for specific cellular components. In addition, the predicted
      modules are enriched with coexpressed proteins. These modules are found to be
      useful for annotating unknown genes and uncovering novel functions of known
      genes. MC(2) is efficient, and takes only about 5 min to identify modules from
      the current yeast gene interaction network with a typical PC (Intel Xeon 2.5 GHz
      CPU and 512 MB memory). The CPU time of MC(2) is affordable (12 h) even when the
      number of interactions is increased by a factor of 10. MC(2) and its results are
      publicly available on http://theory.med.buffalo.edu/MC2.

PMID- 16602687
TI  - Strategy for simulation of CID spectra of N-linked oligosaccharides toward
      glycomics.
AB  - To develop a novel glycomics tool that can enable anyone to identify
      oligosaccharides very easily and quickly, we have recently constructed a library
      of observed multistage tandem mass (MS(n)) spectra for oligosaccharides. However,
      this approach requires the preparation of a large variety of structurally defined
      oligosaccharides. Therefore, simulation of the tandem mass spectrum for any given
      structure would be another powerful approach with which to improve the above
      method. By performing collision-induced dissociation (CID) experiments of sets of
      oligosaccharides complementarily labeled with (13)C(6)-D-galactose, we identified
      characteristic fragment patterns for each branch type of N-linked
      oligosaccharides. On the basis of these characteristic fragment patterns, we
      could simulate CID spectra for three isomeric oligosaccharides. In addition, we
      successfully demonstrated the identification of an oligosaccharide by matching
      its CID spectrum against the library of simulated tandem mass spectra. This
      strategy will be a useful tool for glycomics, as well as for approaches based on
      the library of observed MS(n) spectra.

PMID- 16602688
TI  - Affinity proteomic approach for identification of an IgA-like protein in
      Litopenaeus vannamei and study on its agglutination characterization.
AB  - An unknown protein reacted with anti-human IgA, namely, IgA-like protein, has
      been reported in shrimp, but information regarding its identification is not
      available. In the present study, an affinity proteomic strategy was applied to
      identify the IgA-like protein of shrimp Litopenaeus vannamei. The protein of 75
      kDa was isolated and confirmed by affinity chromatography and Western blotting
      with goat anti-human IgA, respectively, and then identified as hemocyanin, a
      member of IgSF, by mass spectrometry. Moreover, our results showed that human IgA
      and L. vannamei hemocyanin could separately react with goat anti-human IgA or
      rabbit anti-shrimp affinity hemocyanin (a-hemocyanin). Further evidences
      indicated that the recombinant protein of the Ig-like conserved domain could
      react with anti-human IgA. Interestingly, our results indicated that L. vannamei
      hemocyanin could aggregate with eight species of shrimp pathogenic bacteria and
      four types of animal erythrocytes directly. These results indicate that L.
      vannamei hemocyanin, an IgA-like protein, has dual function of reaction with anti
      human IgA as an antigen and of activity binding to bacteria and animal
      erythrocytes as an agglutinin, suggesting its characteristic role as an IgSF
      molecule. In addition, our approach suggests that affinity proteomics based on
      heterogeneous antibody can speed up the identification of Fossman antigens.

PMID- 16602689
TI  - Top-down proteomic analysis of the soluble sub-proteome of the obligate
      thermophile, Geobacillus thermoleovorans T80: insights into its cellular
      processes.
AB  - We report the first analysis of the soluble sub-proteome of the obligate
      thermophile, Geobacillus thermoleovorans T80, utilizing a robust multidimensional
      protein identification protocol. A total of 1,336 proteins were initially
      identified utilizing automated MS/MS identification software. Intensive manual
      curation resulted in a final list containing a total of 294 unique proteins.
      Physiochemical characterization and functional classification of the soluble sub
      proteome was carried out. The strategy has allowed us to gain an insight into the
      cellular processes of this obligate thermophile, identifying a variety of
      proteins known to play a role in stress response. Included within these were a
      number of sigma factors such as sigma(A) that initiate transcription of the heat
      shock operons controlled by the HrcA-CIRCE complex within gram positive bacteria.
      In addition, it has enabled us to assign a degree of functionality to 29 out of
      36 gene products detected in this study that were hitherto described as being
      only hypothetical conserved proteins.

PMID- 16602690
TI  - Identification of proteins from non-model organisms using mass spectrometry:
      application to a hibernating mammal.
AB  - A major challenge in the life sciences is the extraction of detailed molecular
      information from plants and animals that are not among the handful of
      exhaustively studied "model organisms." As a consequence, certain species with
      novel phenotypes are often ignored due to the lack of searchable databases,
      tractable genetics, stock centers, and more recently, a sequenced genome.
      Characterization of phenotype at the molecular level commonly relies on the
      identification of differentially expressed proteins by combining database
      searching with tandem mass spectrometry (MS) of peptides derived from protein
      fragmentation. However, the identification of short peptides from nonmodel
      organisms can be hampered by the lack of sufficient amino acid sequence homology
      with proteins in existing databases; therefore, a database search strategy that
      encompasses both identity and homology can provide stronger evidence than a
      single search alone. The use of multiple algorithms for database searches may
      also increase the probability of correct protein identification since it is
      unlikely that each program would produce false negative or positive hits for the
      same peptides. In this study, four software packages, Mascot, Pro ID, Sequest,
      and Pro BLAST, were compared in their ability to identify proteins from the
      thirteen-lined ground squirrel (Spermophilus tridecemlineatus), a hibernating
      mammal that lacks a completely sequenced genome. Our results show similarities as
      well as the degree of variability among different software packages when the
      identical protein database is searched. In the process of this study, we
      identified the up-regulation of succinyl CoA-transferase (SCOT) in the heart of
      hibernators. SCOT is the rate-limiting enzyme in the catabolism of ketone bodies,
      an important alternative fuel source during hibernation.

PMID- 16602691
TI  - Novel prefractionation method can be used in proteomic analysis.
AB  - For the first time, a novel prefractionation method used in proteomic analysis
      was developed, which is performed by a novel aqueous two-phase system (NATPS)
      composed of n-butanol, (NH(4))(2)SO(4), and water. It can separate proteomic
      proteins into multigroups by one-step extraction. The phase-separation conditions
      of n-butanol solutions were studied in the presence of commonly used inorganic
      salts. The NATPS was subsequently developed. Using human serum albumin, zein, and
      gamma-globulin as model proteins, the separation effectiveness of the NATPS for
      protein was studied under affection factors, i.e., pH, n-butanol volume, protein,
      or salt concentration. The model and actual protein samples were separated by the
      NATPS and then directly used for gel electrophoresis without separating the
      target proteins from phase-forming reagents. It revealed that the NATPS could
      separate proteomic proteins into multigroups by one-step extraction. The NATPS
      has the advantages of rapidity, simplicity, low cost, biocompability, and high
      efficiency. It need not separate target proteins from the phase-forming reagents.
      The NATPS has great significance in separation and extraction of proteomic
      proteins, as well as in methodology.

PMID- 16602692
TI  - Proteomic analysis reveals novel molecules involved in insulin signaling pathway.
AB  - The binding of insulin to its receptor triggers a signaling cascade regulated by
      protein complexes via tyrosine phosphorylation events on a multitude of
      associated proteins. To search novel phosphotyrosine proteins or associated
      proteins involved in insulin signaling pathway, we employed a method in which
      Rat1 cells stably expressing the human insulin receptor were stimulated with or
      without insulin and sub-fractionated prior to enrichment of phosphotyrosine
      proteins by immunoprecipitation and analysis by LC-MS/MS. Bioinformatic analysis
      and manual confirmation of peptide phosphorylation site assignments led to
      identification of 35 phosphotyrosine sites derived from 31 protein groups. Over
      50% of these proteins were reported for the first time as tyrosine
      phosphorylated, including gigaxonin, XIAP and CDK10. In addition, we also found
      that calcium/calmodulin-dependent protein serine kinase (CASK), a key protein in
      protein-targeting and vesicle transport in neurons, forms a complex with two
      unidentified phosphotyrosine proteins pp100 and pp95 in response to insulin
      stimulation, though CASK is not itself tyrosine phosphorylated. Furthermore,
      insulin was able to decrease CASK nuclear location, as well as down-regulate the
      expression of CASK targeted genes. Our results imply CASK as a novel joint knot
      connecting CASK-mediated pathways with the insulin signaling. Our data provide a
      wealth of information potentially paving the way to identify new components in
      the insulin signaling network.

PMID- 16602693
TI  - Pilot study using SELDI-TOF-MS based proteomic profile for the identification of
      diagnostic biomarkers of thyroid proliferative diseases.
AB  - Biomarkers for thyroid cancer (TCa) lack specificity. To develop TCa specific
      biomarkers, SELDI-TOF-MS was used to examine the proteomic profile of biopsies
      obtained from papillary TCa along with adjacent normal tissue. Sixty-three
      potential biomarkers were categorized by univariate analysis into single
      biomarker candidates and segregated by multivariate analysis into normal and
      cancerous groups. Our studies demonstrate the sensitivity and reproducibility of
      this approach to detect biomarkers for TCa.

PMID- 16602694
TI  - Differential protein profiling of primary versus immortalized human RPE cells
      identifies expression patterns associated with cytoskeletal remodeling and cell
      survival.
AB  - Functional research of retinal pigment epithelium (RPE) most often relies on
      utilization of RPE-derived cell lines in vitro. However, no studies about
      similarities and differences of the respective cell lines exist so far. Thus, we
      here analyze the proteome of the most popular RPE cell lines: ARPE-19 and hTERT
      and compare their constitutive and de novo synthesized protein expression
      profiles to human early passage retinal pigment epithelial cells (epRPE) by 2-D
      electrophoresis and MALDI-TOF peptide mass fingerprinting. In all three cell
      lines the baseline protein expression pattern corresponded well to the de novo
      synthesized cellular proteome. However, comparison of the protein profile of
      epRPE cells with that of hTERT-RPE cells revealed a higher abundance of proteins
      related to cell migration, adhesion, and extracellular matrix formation,
      paralleled by a down-regulation of proteins attributed to cell polarization, and
      showed an altered expression of detoxification enzymes in hTERT-RPE. ARPE-19
      cells, however, exhibited a higher abundance of components of the microtubule
      cytoskeleton and differences in expression of proteins related to proliferation
      and cell death. epRPE cells, hTERT-RPE, and ARPE-19 therefore may respond
      differently with respect to certain functional properties, a finding that should
      prove valuable for future in vitro studies.

PMID- 16602695
TI  - Conservation of intrinsic disorder in protein domains and families: I. A database
      of conserved predicted disordered regions.
AB  - Many protein regions have been shown to be intrinsically disordered, lacking
      unique structure under physiological conditions. These intrinsically disordered
      regions are not only very common in proteomes, but also crucial to the function
      of many proteins, especially those involved in signaling, recognition, and
      regulation. The goal of this work was to identify the prevalence,
      characteristics, and functions of conserved disordered regions within protein
      domains and families. A database was created to store the amino acid sequences of
      nearly one million proteins and their domain matches from the InterPro database,
      a resource integrating eight different protein family and domain databases.
      Disorder prediction was performed on these protein sequences. Regions of sequence
      corresponding to domains were aligned using a multiple sequence alignment tool.
      From this initial information, regions of conserved predicted disorder were found
      within the domains. The methodology for this search consisted of finding regions
      of consecutive positions in the multiple sequence alignments in which a 90% or
      more of the sequences were predicted to be disordered. This procedure was
      constrained to find such regions of conserved disorder prediction that were at
      least 20 amino acids in length. The results of this work included 3,653 regions
      of conserved disorder prediction, found within 2,898 distinct InterPro entries.
      Most regions of conserved predicted disorder detected were short, with less than
      10% of those found exceeding 30 residues in length.

PMID- 16602697
TI  - Secretory protein enrichment and analysis: an optimized approach applied on
      cancer cell lines using 2D LC-MS/MS.
AB  - Reliable methods for profiling secretory proteins are highly desirable for the
      identification of biomarkers of disease progression. Secreted proteins are often
      masked by high amounts of protein supplements in the culture medium. We have
      developed an efficient method for the enrichment and analysis of the secretome of
      different cancer cell lines, free of essential contaminants. The method is based
      on the optimization of cell incubation conditions in protein-free medium.
      Secreted proteins are concentrated and fractionated using a reversed-phase tC2
      Sorbent, followed by peptide mass fingerprinting for protein identification. An
      average of 88 proteins were identified in each cancer cell line, of which more
      than 76% are known to be secreted, possess a signal peptide or a transmembrane
      domain. Given the importance of secreted proteins as a source for early detection
      and diagnosis of disease, this approach may help to discover novel candidate
      biomarkers with potential clinical significance.

PMID- 16602696
TI  - Conservation of intrinsic disorder in protein domains and families: II. functions
      of conserved disorder.
AB  - Regions of conserved disorder prediction (CDP) were found in protein domains from
      all available InterPro member databases, although with varying frequency. These
      CDP regions were found in proteins from all kingdoms of life, including viruses.
      However, eukaryotes had 1 order of magnitude more proteins containing long
      disordered regions than did archaea and bacteria. Sequence conservation in CDP
      regions varied, but was on average slightly lower than in regions of conserved
      order. In some cases, disordered regions evolve faster than ordered regions, in
      others they evolve slower, and in the rest they evolve at roughly the same rate.
      A variety of functions were found to be associated with domains containing
      conserved disorder. The most common were DNA/RNA binding, and protein binding.
      Many ribosomal proteins also were found to contain conserved disordered regions.
      Other functions identified included membrane translocation and amino acid storage
      for germination. Due to limitations of current knowledge as well as the
      methodology used for this work, it was not determined whether these functions
      were directly associated with the predicted disordered region. However, the
      functions associated with conserved disorder in this work are in agreement with
      the functions found in other studies to correlate to disordered regions. We have
      established that intrinsic disorder may be more common in bacterial and archaeal
      proteins than previously thought, but this disorder is likely to be used for
      different purposes than in eukaryotic proteins, as well as occurring in shorter
      stretches of protein. Regions of predicted disorder were found to be conserved
      within a large number of protein families and domains. Although many think of
      such conserved domains as being ordered, in fact a significant number of them
      contain regions of disorder that are likely to be crucial to their functions.

PMID- 16602698
TI  - Computational methods for comparison of large genomic and proteomic datasets
      reveal protein markers of metastatic cancer.
AB  - Large-scale genomic and proteomic analysis has provided a wealth of information
      on biologically relevant systems, and the ability to analyze this information is
      crucial to uncovering important biological relationships. However, it has proven
      difficult to compare large datasets from different sources due to different gene
      and protein identifiers assigned by individual laboratories and database systems.
      Here, we describe the design of a fully automated blast program (BlastPro) that
      facilitates rapid comparison of large protein-protein, nucleotide--nucleotide, or
      nucleotide--protein datasets from numerous, independent studies. Using this
      system, we compared several published genomic and proteomic databases for
      proteins that are upregulated in highly motile, metastatic tumor cells. Analysis
      of five independent studies comprised of greater than 1 x 10(6) genomic sequences
      and greater than 1,000 proteins revealed that the cytoskeletal-associated protein
      alpha-actinin is increased at both the mRNA and protein level in metastatic
      breast, prostate, and skin cancer cells. Interestingly, spatial analysis of alpha
      actinin expression revealed that it is amplified 8-fold in the leading
      pseudopodium compared to the cell body compartment of migrating cells. These
      findings indicate that amplification of alpha-actinin and its localization to the
      leading pseudopodium are potential biomarkers of cancer progression to a more
      metastatic phenotype. Together, our results demonstrate that the BlastPro system
      can be used to compare large genomic and proteomic datasets to reveal important
      biological relationships including those associated with cancer progression.

PMID- 16602699
TI  - Proteomic analysis of the mode of antibacterial action of silver nanoparticles.
AB  - Silver nanoparticles (nano-Ag) are potent and broad-spectrum antimicrobial
      agents. In this study, spherical nano-Ag (average diameter = 9.3 nm) particles
      were synthesized using a borohydride reduction method and the mode of their
      antibacterial action against E. coli was investigated by proteomic approaches (2
      DE and MS identification), conducted in parallel to analyses involving solutions
      of Ag(+) ions. The proteomic data revealed that a short exposure of E. coli cells
      to antibacterial concentrations of nano-Ag resulted in an accumulation of
      envelope protein precursors, indicative of the dissipation of proton motive
      force. Consistent with these proteomic findings, nano-Ag were shown to
      destabilize the outer membrane, collapse the plasma membrane potential and
      deplete the levels of intracellular ATP. The mode of action of nano-Ag was also
      found to be similar to that of Ag(+) ions (e.g., Dibrov, P. et al, Antimicrob.
      Agents Chemother. 2002, 46, 2668-2670); however, the effective concentrations of
      nano-Ag and Ag(+) ions were at nanomolar and micromolar levels, respectively.
      Nano-Ag appear to be an efficient physicochemical system conferring antimicrobial
      silver activities.

PMID- 16602700
TI  - Beyond linker histones and high mobility group proteins: global profiling of
      perchloric acid soluble proteins.
AB  - Extraction with HClO(4) provides an easy method for efficient enrichment of both
      histone H1 and HMG proteins from a variety of tissues. Usually, the histone and
      the HMG proteins are the most abundant components of the extracts, however, other
      proteins have frequently been observed but only seldom studied in more detail.
      Here we describe a study aimed at global characterization of HClO(4) extractable
      proteins from breast cancer cell lines. We report identification of 150 unique
      proteins by liquid chromatography tandem mass spectrometry including almost all
      major histone H1 variants and canonical members of the HMG protein families. In
      the extracts, diverse proteins with HMG-like amino acid composition were
      identified and their post-translational modifications were mapped. Importantly,
      those include multiple proteins known or supposed to be related to cell
      proliferation and cancer. Since purification of these proteins as well as low
      abundant variants of histone and HMG proteins is difficult due to their metabolic
      instability, characterization of these proteins from crude extracts can
      facilitate studies aimed at better understanding of their function.

PMID- 16602701
TI  - Modification-specific proteomics of plasma membrane proteins: identification and
      characterization of glycosylphosphatidylinositol-anchored proteins released upon
      phospholipase D treatment.
AB  - Plasma membrane proteins are displayed through diverse mechanisms, including
      anchoring in the extracellular leaflet via glycosylphosphatidylinositol (GPI)
      molecules. GPI-anchored membrane proteins (GPI-APs) are a functionally and
      structurally diverse protein family, and their importance is well-recognized as
      they are candidate cell surface biomarker molecules with potential diagnostic and
      therapeutic applications in molecular medicine. GPI-APs have also attracted
      interest in plant biotechnology because of their role in root development and
      cell remodeling. Using a shave-and-conquer concept, we demonstrate that
      phospholipase D (PLD) treatment of human and plant plasma membrane fractions
      leads to the release of GPI-anchored proteins that were identified and
      characterized by capillary liquid chromatography and tandem mass spectrometry. In
      contrast to phospholipase C, the PLD enzyme is not affected by structural
      heterogeneity of the GPI moiety, making PLD a generally useful reagent for
      proteomic investigations of GPI-anchored proteins in a variety of cells, tissues,
      and organisms. A total of 11 human GPI-APs and 35 Arabidopsis thaliana GPI-APs
      were identified, representing a significant addition to the number of
      experimentally detected GPI-APs in both species. Computational GPI-AP sequence
      analysis tools were investigated for the characterization of the identified GPI
      APs, and these demonstrated that there is some discrepancy in their efficiency in
      classification of GPI-APs and the exact assignment of omega-sites. This study
      highlights the efficiency of an integrative proteomics approach that combines
      experimental and computational methods to provide the selectivity, specificity,
      and sensitivity required for characterization of post-translationally modified
      membrane proteins.

PMID- 16602702
TI  - Molecular profiling of hepatocellular carcinoma in mice with a chronic deficiency
      of hepatic s-adenosylmethionine: relevance in human liver diseases.
AB  - S-adenosylmethionine arises as a central molecule in the preservation of liver
      homeostasis as a chronic hepatic deficiency results in spontaneous development of
      steatohepatitis and hepatocellular carcinoma. In the present work, we have
      attempted a comprehensive analysis of proteins associated with
      hepatocarcinogenesis in MAT1A knock out mice using a combination of two
      dimensional electrophoresis and mass spectrometry, to then apply the resulting
      information to identify hallmarks of human HCC. Our results suggest the existence
      of individual-specific factors that might condition the development of
      preneoplastic lesions. Proteomic analysis allowed the identification of 151
      differential proteins in MAT1A-/- mice tumors. Among all differential proteins,
      27 changed in at least 50% of the analyzed tumors, and some of these alterations
      were already detected months before the development of HCC in the KO liver. The
      expression level of genes coding for 13 of these proteins was markedly decreased
      in human HCC. Interestingly, seven of these genes were also found to be down
      regulated in a pretumoral condition such as cirrhosis, while depletion of only
      one marker was assessed in less severe liver disorders.

PMID- 16602703
TI  - Proteome of conidial surface associated proteins of Aspergillus fumigatus
      reflecting potential vaccine candidates and allergens.
AB  - Aspergillus fumigatus is a mold causing most of the invasive fungal lung
      infections in the immunocompromised host. In addition, the species is the
      causative agent of certain allergic diseases. Both in invasive and in allergic
      diseases, the conidial surface mediates the first contact with the human immune
      system. Thus, conidial surface proteins may be reasonable vaccine candidates as
      well as important allergens. To broaden the list of those antigens, intact viable
      Aspergillus conidia were extracted with mild alkaline buffer at pH 8.5 in the
      presence of a 1,3-beta-glucanase. The proteome of this fraction was separated by
      two- dimensional gel electrophoresis (2-DE) and analyzed by liquid chromatography
      coupled with tandem mass spectrometry. Altogether 26 different A. fumigatus
      proteins were identified, twelve of which contain a signal for secretion. Among
      these were the known major conidial surface protein rodlet A, one acid protease
      PEP2, one lipase, a putative disulfide isomerase and a putative fructose-1,6
      biphosphatase. The known allergen Aspf 3 was identified among the proteins
      without a signal for secretion. On the basis of the recently annotated A.
      fumigatus genome (Nature 2005, 438, 1151-1156), proteome analysis is now a
      powerful tool to confirm expression of hypothetical proteins and, thereby to
      identify additional vaccine candidates and possible new allergens of this
      important fungal pathogen.

PMID- 16602704
TI  - Characterization of the maize xylem sap proteome.
AB  - The xylem in plants has mainly been described as a conduit for water and
      minerals, but emerging evidence also indicates that the xylem contains protein.
      To study the proteins in xylem sap, we characterized the identity and composition
      of the maize xylem sap proteome. The composition of the xylem sap proteome in
      maize revealed proteins related to different phases of xylem differentiation
      including cell wall metabolism, secondary cell wall synthesis, and programmed
      cell death. Many proteins were found to be present as multiple isoforms and some
      of these isoforms are glycosylated. Proteins involved in defense mechanisms were
      also present in xylem sap and the sap proteins were shown to have antifungal
      activity in bioassays.

PMID- 16602705
TI  - Novel protein phosphorylation site identification in spinach stroma membranes by
      titanium dioxide microcolumns and tandem mass spectrometry.
AB  - In this work, spinach stroma membrane, instead of thylakoid, has been
      investigated for the presence of phosphorylated proteins. We identified seven
      previously unknown phosphorylation sites by taking advantage of TiO(2)
      phosphopeptides enrichment coupled to mass spectrometric analysis. Upon
      illumination at 100 micromol m(-2) s(-1), two novel phosphopeptides belonging to
      the N-terminal region of Lhcb1 light-harvesting protein were detected:
      NVSSGS(p)PWYGPDR and T(p)VQSSSPWYGPDR. Moreover, three new threonine residues in
      CP43 (Thr-6, Thr-8, and Thr-346) and, for the first time, two amino acid residues
      of the N-terminus of Rieske Fe-S protein of the cytochrome b(6)f complex (Thr-2
      and Ser-3) were revealed to be phosphorylated. Since Lhcb1 and CP43 have been
      reported as mobile proteins, it may be suggested that illumination derived
      phosphorylation, and consequently the addition of negatively charged groups to
      the protein, is a necessary condition to induce a significant protein structural
      change.

PMID- 16602706
TI  - Simultaneous reduction and alkylation of protein disulfides in a centrifugal
      ultrafiltration device prior to two-dimensional gel electrophoresis.
AB  - Reduction and alkylation of protein disulfides prior to IEF, when performed
      directly in a centrifugal ultrafiltration device, provides an effective means of
      terminating the alkylation reaction, concentrating the proteins for analysis, and
      removing ionic impurities that interfere with IEF. When cells were lysed in
      "buffers" that support the activity of enzymes such as lysozyme and benzonase,
      the conductivity of the resulting lysate was an order of magnitude higher than
      when lysis was induced by chaotropic urea detergent solutions. Following
      reduction and alkylation, the conductivity of both lysates was lowered by
      ultrafiltration to the 0.1-0.2 mS/cm range in preparation for IEF. The detergent
      3-(4-heptyl)phenyl 3-hydroxypropyl dimethylammonio propanesulfonate (C7BzO),
      which favors the solubilization of proteins, but which interferes with SDS
      equilibration and second dimension PAGE, was effectively removed by
      ultrafiltration and exchanged with CHAPS without measurable loss of protein.
      Disparate protein patterns of Rhodopseudomonas palustris lysates were revealed by
      two-dimensional gel electrophoresis depending on which reagent was used to induce
      cell lysis.

PMID- 16602707
TI  - Modular stop and go extraction tips with stacked disks for parallel and
      multidimensional Peptide fractionation in proteomics.
AB  - Proteome complexity necessitates protein or peptide separation prior to analysis.
      We previously described a pipet-tip based peptide micropurification system named
      StageTips (STop and Go Extraction Tips), which consists of a very small disk of
      membrane-embedded separation material. Here, we extend this approach in several
      dimensions by stacking disks containing reversed phase (C(18)) and strong cation
      exchange (SCX) materials. Multidimensional fractionation as well as desalting,
      filtration, and concentration prior to mass spectrometry in single or tandem
      columns is described. C(18)-SCX-C(18) stacked disks significantly improved
      protein identification by LC-MS/MS for an E. coli protein digest and by MALDI-MS
      for a 12 standard protein digest. Sequential fractionation based on C(18)-
      followed by SCX material was also developed. This multidimensional fractionation
      approach was expanded to parallel sample preparation by incorporating C(18)-SCX
      StageTips into a 96-well plate (StagePlate). Fractions were collected into other
      C(18)-StagePlates and desalted and eluted in parallel to sample well plates or
      MALDI targets. This approach is suitable for high throughput protein
      identification for moderately complex, low abundance samples using automated
      nanoelectrospray-MS/MS or MALDI-MS.

PMID- 16602708
TI  - Metabonomic study of aristolochic acid-induced nephrotoxicity in rats.
AB  - This paper describes a metabonomic study characterizing the nephrotoxicity
      induced by aristolochic acid (AA), a suspected kidney toxicant. For these
      studies, we examined the biochemical compositions of AA-treated rat urine using
      LC-MS and pattern recognition methods. The biochemical and histological patterns
      of rat groups treated with different AA sources showed distinct differences from
      those of the control group. Certain metabolic pathways, such as homocysteine
      formation and the folate cycle were significantly accelerated, while others,
      including arachidonic acid biosynthesis, were decreased. A subset-validation
      procedure using linear discriminant analysis (LDA) and selected predictive
      variables indicated that approximately 95% of the treated and nontreated rat
      urine samples were classified correctly into their respective treatment groups.
      The results suggested that this metabonomic approach is a promising methodology
      for the rapid in vivo screening of nephrotoxicity associated with ingesting multi
      ingredient medicinal herb supplements, and provides a valid method for
      comprehending the chemical-induced perturbations in the metabolic network and the
      networked lesions.

PMID- 16602709
TI  - Trade-off between high sensitivity and increased potential for false positive
      peptide sequence matches using a two-dimensional linear ion trap for tandem mass
      spectrometry-based proteomics.
AB  - Two-dimensional linear ion trap mass spectrometers are rapidly becoming the new
      workhorse instruments for shotgun proteomic analysis of complex peptide mixtures.
      The objective of this study was to compare the potential for false positive
      peptide sequence matches between a two-dimensional ion trap instrument and a
      traditional, three-dimensional ion trap instrument. Through the comparative
      analysis of a complex protein sample, we found that in order to minimize false
      positive sequence matches, sequence match scoring criteria must be more stringent
      for data from the two-dimensional ion trap compared to the three-dimensional ion
      trap data. Given this increased potential for false positives, we also
      investigated two potential filtering strategies to reduce the false positive
      matches for data derived from the two-dimensional ion trap, including trypsin
      enzyme cleavage filtering, and the addition of peptide physicochemical
      information as a constraint, specifically peptide isoelectric point. The results
      described here provide a cautionary tale to researchers, demonstrating the need
      for careful analysis of MS/MS data from this new class of ion trap instruments,
      as well as the effectiveness of trypsin enzyme cleavage filtering and peptide pI
      information in maximizing high confidence protein identifications from this
      powerful proteomic instrumentation.

PMID- 16602710
TI  - Determination of beta-amyloid peptide signatures in cerebrospinal fluid using
      immunoprecipitation-mass spectrometry.
AB  - Early pathogenic events in Alzheimer's disease (AD) involve increased production
      and/or reduced clearance of beta-amyloid (Abeta), especially the 42 amino acid
      fragment Abeta1-42. The Abeta1-42 peptide is generated through cleavage of the
      amyloid precursor protein by beta- and gamma-secretase and is catabolised by a
      variety of proteolytic enzymes such as insulin-degrading enzyme and neprilysin.
      Here, we describe a method that employs immunoprecipitation combined with matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry to
      determine the pattern of C-terminally truncated Abeta peptides in cerebrospinal
      fluid (CSF). Using antibodies coupled to magnetic beads, we have detected 18 C
      terminally and 2 N-terminally truncated Abeta peptides in CSF. By determining the
      identity and profile of the truncated Abeta peptides, more insight may be gained
      about differences in the metabolism and structural properties of Abeta in AD.
      Finally, the Abeta fragment signatures may prove useful as a diagnostic test for
      AD.

PMID- 16602713
TI  - Modulation of single-chain antibody affinity with temperature-responsive elastin
      like polypeptide linkers.
AB  - Single-chain antibodies are genetically engineered constructs composed of a VH
      and VL domain of an antibody linked by a flexible peptide linker, commonly
      (GGGGS)3. We asked whether replacement of this flexible linker with peptides
      known to undergo environmentally induced structural transitions could lead to
      antibodies with controlled binding and release characteristics. To this end, we
      genetically modified and produced a series of anti-fluorescein single-chain
      antibodies with the general linker sequence (VPGXG)n, where n is 1.2 to 3 and X
      is Val or His, to evaluate the effects of linker length and composition. Our
      results indicate that single-chain antibodies containing elastin-like polypeptide
      linkers have equilibrium affinity (KD) comparable to wild-type (GGGGS)3 at room
      temperature but altered binding kinetics and faster ligand release as the
      temperature is raised. These results are consistent with the increased molecular
      order and contraction that elastin-like polypeptides are known to undergo with
      increased temperature. Modulation of antibody affinity using stimulus-responsive
      linkers may have applications in biosensors, drug delivery, and bioseparations.

PMID- 16602711
TI  - Decoy peptides that bind dynorphin noncovalently prevent NMDA receptor-mediated
      neurotoxicity.
AB  - Prodynorphin-derived peptides elicit various pathological effects including
      neurological dysfunction and cell death. These actions are reduced by N-methyl-d
      aspartate receptor (NMDAR) but not opioid receptor antagonists suggesting NMDAR
      mediation. Here, we show that a conserved epitope (KVNSEEEEEDA) of the NR1
      subunit of the NMDAR binds dynorphin peptides (DYNp) noncovalently. Synthetic
      peptides containing this epitope form stable complexes with DYNp and prevent the
      potentiation of NMDAR-gated currents produced by DYNp. They attenuate DYNp-evoked
      cell death in spinal cord and prevent, as well as reverse, DYNp-induced paralysis
      and allodynia. The data reveal a novel mechanism whereby prodynorphin-derived
      peptides facilitate NMDAR function and produce neurotoxicity. Furthermore, they
      suggest that synthetic peptides that bind DYNp, thus preventing their interaction
      with NMDAR, may be novel therapeutic agents for the treatment of spinal cord
      injury.

PMID- 16602714
TI  - Metallopolymer-peptide conjugates: synthesis and self-assembly of
      polyferrocenylsilane graft and block copolymers containing a beta-sheet forming
      Gly-Ala-Gly-Ala tetrapeptide segment.
AB  - We describe the synthesis and self-assembly of two beta-sheet forming
      metallopolymer-peptide conjugates. The ability of the oligotetrapeptide sequence
      Gly-Ala-Gly-Ala (GAGA) to form antiparallel beta-sheets was retained in PFS-b
      AGAG (PFS = polyferrocenylsilane) and PFS-g-AGAG conjugates with block and graft
      architectures, respectively. In the solid state, DSC experiments suggest a phase
      separation between the peptide and PFS domains. In toluene, PFS-b-AGAG
      interestingly forms a fibrous network which consists of a core containing the
      self-assembled antiparallel beta-sheet peptide and a corona of organometallic
      PFS. The self-assembly of the peptide into antiparallel beta-sheets is the
      driving force for the fiber formation, whereas PFS prevents uncontrolled lateral
      aggregation of the fibers. The use of an oligopeptide to self-assemble an
      otherwise random coiled organometallic polymer may be a useful strategy to
      enhance nanostructure formation. In the cases described here, the conjugates may
      be used to create nanopatterned ceramics, and the redox properties of the
      resulting supramolecular aggregates are of significant interest.

PMID- 16602715
TI  - Solid-phase synthesis and kinetic characterization of fluorogenic enzyme
      degradable hydrogel cross-linkers.
AB  - Of critical importance in drug delivery and tissue engineering applications is
      the degradability of implanted polymeric materials. The use of peptide-derived
      cross-linkers in hydrogel design is a valuable approach by which polymeric
      carriers can be endowed with enzymatic degradability in a predictable,
      "programmable" fashion. The solid-phase synthesis strategy described herein
      allows for an expeditious, flexible synthesis of bis-acrylamide-derivatized
      peptides with complex modifications, as exemplified by the incorporation of
      fluorophore and quencher moieties into a matrix metalloprotease (MMP)-degradable
      cross-linker. The crude synthetic product was obtained in high yield and purity
      and purified by standard methods; it was then used directly for polymerization
      without the need for tedious and often nonchemoselective solution-phase
      modifications. Functional appendages incorporated for detection provided a
      direct, quantitative link between enzymatic activity and hydrogel degradation
      using routine methods for identification of optimal enzyme-specific
      degradability.

PMID- 16602716
TI  - Effects of polyols, saccharides, and glycoproteins on thermoprecipitation of
      phenylboronate-containing copolymers.
AB  - The copolymer of 3-(acrylamido)phenylboronic acid and N-isopropylacrylamide
      (82:18, Mn = 47000 g/mol) was prepared by free radical polymerization. The
      copolymer showed typical thermoprecipitation behavior in aqueous solutions; its
      phase transition temperature (TP) was 26.5 +/- 0.2 degrees C in 0.1 M glycine
      NaOH buffer containing 0.1 M NaCl, pH 9.2. Due to specific complex formation of
      the pendant boronates with sugars, TP was strongly affected by the type of sugar
      and its concentration at pH 9.2. Fructose, lactulose, and glucose caused the
      largest increase in TP (up to 4 degrees C) at 0.56 mM concentration, attributed
      to the high binding affinity of the sugars to borate and phenylboronate. Among
      the sugars typical of nonreducing ends of oligosaccharides, N-acetylneuraminic
      acid had the strongest effect on TP (ca. 2 degrees C at 0.56 mM concentration and
      pH 9.2), while the effects of other sugars are well expressed at the higher
      concentrations (16 and 80 mM) and decreased in the order xylose approximately
      galactose >or= N-acetyllactosamine >or= mannose approximately fucose >> N
      acetylglucosamine. The effect exerted on the phase transition by glycoproteins
      was the strongest with mucin from porcine stomach and decreased in the series
      mucin > horseradish peroxidase > human gamma-globulin at pH 9.2. As a first
      approximation, the weight percentage and/or the number of oligosaccharides in
      glycoproteins determined the character of their interaction with the pendant
      phenylboronates and, therefore, the effect on the copolymer phase transition.

PMID- 16602717
TI  - Effects of polyelectrolyte chain stiffness, charge mobility, and charge sequences
      on binding to proteins and micelles.
AB  - The binding affinities of polyanions for bovine serum albumin in NaCl solutions
      from I = 0.01-0.6 M, were evaluated on the basis of the pH at the point of
      incipient binding, converting each such pH(c) value into a critical protein
      charge Zc. Analogous values of critical charge for mixed micelles were obtained
      as the cationic surfactant mole fraction Yc. The data were well fitted as Yc or
      Zc = KI a, and values of K and a were considered as a function of normalized
      polymer charge densities (tau), charge mobility, and chain stiffness. Binding
      increased with chain flexibility and charge mobility, as expected from
      simulations and theory. Complex effects of tau were related to intrapolyanion
      repulsions within micelle-bound loops (seen in the simulations) or negative
      protein domain-polyanion repulsions. The linearity of Zc with radicalI at I < 0.3
      M was explained by using protein electrostatic images, showing that Zc at I < 0.3
      M depends on a single positive "patch"; the appearance of multiple positive
      domains I > 0.3 M (lower pH(c)) disrupts this simple behavior.

PMID- 16602718
TI  - Dendritic saccharide surfactant polymers as antifouling interface materials to
      reduce platelet adhesion.
AB  - Here, we report on the synthesis of dendritic saccharide surfactant polymers as
      antifouling interface materials to reduce platelet adhesion. An acetal-protected
      poly(amidoamine) (PAMAM) dendron (5, G = 2) was first synthesized by using
      aminoacetaldehyde dimethyl acetal (1) as the starting material to provide a
      monovalent focal structure with dimethyl acetal-protected aldehyde functionality.
      Maltose dendron (M4, 6) was obtained by reacting the peripheral amine groups of
      acetal-dendron (5) with maltonolactone. The dendritic surfactant polymers (9)
      were then synthesized via a two-step method by sequential addition of maltose
      dendron and hexanal to react with the amine groups on the poly(vinylamine) (PVAm)
      backbone. Surface activity of the amphiphilic glycopolymers at the air/water
      interface was demonstrated by reduction in water surface tension. Adsorption of
      the amphiphilic glycopolymers at the solid/water interface was examined on
      octadecyltrichlorosilane (OTS)-coated coverslips by water contact angle
      measurements. A nanoscale understanding of surface-induced self-assembly of the
      dendritic surfactant polymer on highly oriented pyrolytic graphite (HOPG) was
      gained using AFM operated in fluid tapping mode. A lateral ordering of adsorbing
      surfactant polymer was visualized with a pattern in strands 60 degrees out of
      alignment. The static platelet adhesion tests show that the hexyl side chains can
      facilitate adsorption of the surfactant polymers onto hydrophobic substrates,
      while the maltose dendron side chains can provide a dense canopy of protective
      glycocalyx-like layer as an antifouling interface to reduce platelet adhesion.

PMID- 16602719
TI  - Influence of PEG endgroup and molecular weight on its reactivity for lipase
      catalyzed polyester synthesis.
AB  - Polycondensations were performed at 70 degrees C in bulk using physically
      immobilized lipase B from Candida antarctica (CAL-B) as catalyst. Study of
      copolymerizations between sebacic acid and PEG diols of differing Mn values (200,
      400, 600, 1000, 2000, and 10 000) showed that PEG 400 and 600 were most reactive
      (DP(avg) up to about 6). Increasing the PEG diol chain length from 600 to 1000,
      2000, and 10 000 resulted in large decreases in copolymer DP(avg) values. PEG200
      diacids (i.e., HOOC-(CH2)x-O-(CH2CH2O)n-(CH2)x-COOH) were successfully
      synthesized where x was 1, 4, 5, 7, 9, and 11. Study of copolymerizations of
      these diacids with 1,8-octanediol showed that, by introduction of a five-carbon
      methylene spacer (x = 5), remarkable increases in the reactivity of PEG200
      diacids were achieved. In addition, introduction of this spacer was also
      effective for increasing the reactivity of PEG diacids of higher molecular weight
      (i.e., PEG400, 600, and 1000). This work verified the hypothesis that, by
      conversion of PEG chain ends to structures more closely resembling fatty acids,
      modified PEG building blocks are obtained that are better recognized as
      substrates by CAL-B during condensation reactions.

PMID- 16602720
TI  - Coaxial electrospinning of (fluorescein isothiocyanate-conjugated bovine serum
      albumin)-encapsulated poly(epsilon-caprolactone) nanofibers for sustained
      release.
AB  - As an aim toward developing biologically mimetic and functional nanofiber-based
      tissue engineering scaffolds, we demonstrated the encapsulation of a model
      protein, fluorescein isothiocyanate-conjugated bovine serum albumin (fitcBSA),
      along with a water-soluble polymer, poly(ethylene glycol) (PEG), within the
      biodegradable poly(epsilon-caprolactone) (PCL) nanofibers using a coaxial
      electrospinning technique. By variation of the inner flow rates from 0.2 to 0.6
      mL/h with a constant outer flow rate of 1.8 mL/h, fitcBSA loadings of 0.85-2.17
      mg/g of nanofibrous membranes were prepared. Variation of flow rates also
      resulted in increases of fiber sizes from ca. 270 nm to 380 nm. The encapsulation
      of fitcBSA/PEG within PCL was subsequently characterized by laser confocal
      scanning microscopy, transmission electron microscopy (TEM), and X-ray
      photoelectron spectroscopy (XPS) analysis. In vitro release studies were
      conducted to evaluate sustained release potential of the core-sheath-structured
      composite nanofiber PCL-r-fitcBSA/PEG. As a negative control, composite nanofiber
      PCL/fitcBSA/PEG blend was prepared from a normal electrospinning method. It was
      found that core-sheath nanofibers PCL-r-fitcBSA/PEG pronouncedly alleviated the
      initial burst release for higher protein loading and gave better sustainability
      compared to that of PCL/fitcBSA/PEG nanofibers. The present study would provide a
      basis for further design and optimization of processing conditions to control the
      nanostructure of core-sheath composite nanofibers and ultimately achieve desired
      release kinetics of bioactive proteins (e.g., growth factors) for practical
      tissue engineering applications.

PMID- 16602721
TI  - Development of N,O-(carboxymethyl)chitosan/collagen matrixes as a wound dressing.
AB  - In an attempt to accelerate wound healing by stimulating the recruitment of
      fibroblasts and improve the mechanical properties of collagen matrixes, N,O
      (carboxymethyl)chitosan (NOCC) was incorporated into the backbone of a collagen
      (COL) matrix without or with chondroitin sulfate (CS) or an acellular dermal
      matrix (ADM). The result of a cell migration study demonstrated that the
      migration of fibroblasts was significantly enhanced by NOCC in a concentration
      dependent manner. In the analysis with a dynamic mechanical analyzer, NOCC/CS/COL
      matrixes presented higher tensile strengths than did NOCC/ADM/COL matrixes. Skin
      fibroblasts cultured on the matrixes containing NOCC showed increased
      proliferation and secretion of three kinds of cytokines compared with the
      control. Results of the in vivo wound healing study showed that matrixes
      incorporating NOCC showed markedly enhanced wound healing compared with the
      control. Therefore, the above results clearly suggest that NOCC/COL matrixes
      containing CS or ADM can be potential wound dressings for clinical applications.

PMID- 16602722
TI  - Sensing capabilities of colloidal gold monolayer modified with a phenylboronic
      acid-carrying polymer brush.
AB  - A dithiolated random copolymer with pendent phenylboronic acid residues [Cys
      poly(3-acrylamidophenylboronic acid-co-N,N-dimethylaminopropyl methacrylamide),
      Cys-poly(APBA-co-DMAPMA)] that shows the abilities of initiation, transfer, and
      termination (iniferter) was obtained by using a benzyl N,N-diethyldithiocarbamoyl
      (BDC) derivative. The obtained disulfide-carrying copolymer was accumulated on a
      colloidal gold-immobilized glass substrate, and the usefulness of the polymer
      brush as a sensing element for glycoproteins such as ovalbumin (OVA) was examined
      by UV-visible spectrophotometry with the help of localized surface plasmon
      resonance (LSPR). The sensor showed a concentration-dependent binding of OVA with
      a detection limit of 100 nM, and it had a very high stability at high ionic
      strength. The sensor chip could be used for a detection of another glycoprotein,
      avidin, as well. Furthermore, the binding of biotin-modified human serum albumin
      (biotinylated HSA) to the avidin-phenylboronic acid- (PBA-) carrying polymer
      brush complex and further specific binding of anti-HSA immunoglobulin G to the
      biotinylated HSA-avidin-PBA-carrying polymer brush ternary complex could clearly
      be observed. The polymer-brush-coated device examined here not only was useful as
      a simple sensor chip, but also is expected to open a new perspective on
      interfacial phenomena performed by various functional polymer brushes fixed to
      colloidal gold on glass substrates.

PMID- 16602723
TI  - Honeycomb-structured porous films from polypyrrole-containing block copolymers
      prepared via RAFT polymerization as a scaffold for cell growth.
AB  - Honeycomb-structured porous films were prepared using customized amphiphilic
      block copolymers, synthesized by RAFT polymerization. Pyrrole was templated along
      an amphiphilic block copolymer, composed of polystyrene and poly(acrylic acid).
      Subsequent oxidation of pyrrol to polypyrrole, resulted in the formation of a
      soluble polypyrrole-containing polymer. Gel permeation chromatography and dynamic
      light scattering studies confirmed the solubility of the resulting customized
      amphiphilic block copolymer, in both water and organic solvent, forming either
      micelles or inverse aggregates. Porous films with a hexagonal array of micron
      sized pores were generated with the polymer, using the breath figures templating
      technique. The resulting films were found to be non-cytotoxic and hence suitable
      as scaffolds for tissue engineering. Initial fibroblast cell culture studies on
      these scaffolds demonstrated a dependency of cell attachment on the pore size of
      scaffolds.

PMID- 16602725
TI  - Interaction between covalent DNA gels and a cationic surfactant.
AB  - The interaction of covalently cross-linked double-stranded (ds) DNA gels and
      cetyltrimethylammonium bromide (CTAB) is investigated. The volume transition of
      the gels that follows the absorption of the oppositely charged surfactant from
      aqueous solution is studied. As do other polyelectrolyte networks, DNA networks
      form complexes with oppositely charged surfactant micelles at surfactant
      concentrations far below the critical micelle concentration (cmc) of the polymer
      free solution. The size of the absorbed surfactant aggregates is determined from
      time-resolved fluorescence quenching (TRFQ). At low surfactant concentrations,
      small discrete micelles (160 < N < 210) are found, whereas large micelles (N >
      500) form at surfactant concentrations of 1 mM. When the DNA is in excess of the
      surfactant, the surfactant binding is essentially quantitative. The gel volume
      decreases by 90% when the surfactant to DNA charge ratio, beta, increases from 0
      to 1.

PMID- 16602724
TI  - Bioinert surface of pluronic-immobilized flask for preservation of hematopoietic
      stem cells.
AB  - The bioinert materials on which cells do not proliferate, differentiate, nor de
      differentiate should be useful for the culture and preservation of stem cells.
      The Pluronic F127, a triblock copolymer of ethylene oxide, and propylene oxide
      was activated using carbonyldiimidazole (CDI), and CDI-activated Pluronic was
      subsequently immobilized on the surface of a lysine-coated polystyrene tissue
      culture flask. The morphology of fibroblasts (L929 cells) on the Pluronic
      immobilized flask was spherical, and did not show spreading behavior. This
      observation indicates that L929 cells on the Pluronic-immobilized flask were
      cultured in a bioinert environment. The expression ratio of surface markers on
      hematopoietic stem cells (CD34 and CD133) cultured in the Pluronic-immobilized
      flask was significantly higher than that in polystyrene tissue culture flask and
      commercially available bioinert flask (i.e., low cell binding cultureware). This
      is caused by the existence of hydrophilic segments of Pluronic F127 on the
      Pluronic-immobilized flask.

PMID- 16602726
TI  - Comparison of repetitive sequences derived from high molecular weight subunits of
      wheat glutenin, an elastomeric plant protein.
AB  - A strategy has been developed to create repetitive peptides incorporating
      substitutions in the PGQGQQGYYPTSLQQ consensus repeat sequence of high molecular
      weight subunits in order to investigate natural sequence variations in
      elastomeric proteins of wheat gluten. After introduction of glutamic and aspartic
      acid residues, the peptide behaved similarly to the unmodified form at low pH,
      but became readily water soluble at pH > 6. Substitution of Gln for Leu at
      position 13 resulted in only small changes to the secondary structure of the
      water-insoluble peptides, as did Tyr8His and Thr11Ala. The effects of proline
      substitutions depended on their location: Leu13Pro substitution had little effect
      on solubility and structure, but Gln6Pro substitution resulted in dramatic
      changes. Peptides with two Gln6Pro substitutions had similar properties to the
      water-insoluble parental peptide, but those with 6 or 10 substitutions were
      readily soluble. The results indicated that specific sequences influence
      noncovalent intermolecular interactions in wheat gluten proteins.

PMID- 16602727
TI  - Bilayer fibril formation by genetically engineered polypeptides: preparation and
      characterization.
AB  - A de novo, genetically engineered 687 residue polypeptide expressed in E. coli
      has been found to form highly rectilinear, beta-sheet containing fibrillar
      structures. Tapping-mode atomic force microscopy, deep-UV Raman spectroscopy, and
      transmission electron microscopy definitively established the tendency of the
      fibrils to predominantly display an apparently planar bilayer or ribbon
      assemblage. The ordered self-assembly of designed, extremely repetitive, high
      molecular weight peptides is a harbinger of the utility of similar materials in
      nanoscience and engineering applications.

PMID- 16602728
TI  - Investigation of MC3T3-E1 cell behavior on the surface of GRGDS-coupled chitosan.
AB  - The GRGDS (Gly-Arg-Gly-Asp-Ser) peptide has intermediate affinity to alphaVbeta3
      and alphaIIbbeta3, which are the integrins most reported to be involved in bone
      function. In this study, biomimetic chitosan films modified with GRGDS peptide
      were prepared and were used as a substrate for the in vitro culture of MC3T3-E1
      cells in order to investigate the effect of GRGDS modification on MC3T3-E1 cell
      behavior. The results of electron spectroscopy for chemical analysis (ESCA),
      attenuated total reflection-Fourier transform infrared spectra (ATR-FTIR), and
      amino acid analysis (AAA) demonstrated that the chitosan films were successfully
      modified with GRGDS peptides and that the surface density of the immobilized
      GRGDS was on the order of 10(-9) mol/cm2. The immobilization of the GRGDS
      sequence on chitosan as well as the peptide concentration play a significant role
      in MC3T3-E1 cell behavior. MC3T3-E1 cell attachment, proliferation, migration,
      differentiation, and mineralization were remarkably greater on GRGDS-coupled
      chitosan than on unmodified chitosan. Besides, the degree of acceleration of
      these biological processes was found to be dependent on peptide density.
      Competitive inhibition of MC3T3-E1 cell attachment using soluble GRGDS peptides
      indicated that the interaction of MC3T3-E1 cells with the surface of the
      materials was ligand-specific. Cytoskeleton organization in the fully spread
      MC3T3-E1 cells was highly obvious on GRGDS-coupled chitosan when compared to the
      lack of actin fibers noted in the round MC3T3-E1 cells on unmodified chitosan.
      These results suggest that MC3T3-E1 cell function can be modulated, in a peptide
      density-dependent manner, by the immobilization of GRGDS peptide on chitosan used
      for scaffold-based bone tissue engineering.

PMID- 16602729
TI  - Highly branched poly(N-isopropylacrylamide) for use in protein purification.
AB  - Poly(N-isopropylacrylamide)s with imidazole endgroups were used to separate a
      histidine-tagged protein fragment directly from a crude cell lysate. The polymers
      display a lower critical solution temperature that can be tuned to occur at a
      range of subambient temperatures. UV-visible spectra indicated differences in the
      binding in aqueous media of Cu(II) and Ni(II) to the imidazole endgroups. These
      changes in the UV-visible spectra were reflected in the solution/aggregation
      behavior of the polymers as studied by dynamic light scattering. The addition of
      Cu(II) disaggregated the polymers, and the polymer coil swelled. On the other
      hand, when Ni(II) was added the polymers remained aggregated in aqueous media.
      The polymers were used to purify residues 230-534 of the histidine-tagged breast
      cancer susceptibility protein his6-BRCA1. Cu(II) was found to be better suited to
      the formation of useful polymer-metal ion-protein complexes that display cloud
      points, since Ni(II)/polymer mixtures generated very little purified protein. The
      polymers were synthesized using a previously reported variation of the reversible
      addition-fragmentation chain termination (RAFT) methodology, using the chain
      transfer agent 3H-imidazole-4-carbodithioic acid 4-vinyl benzyl ester with N
      isopropylacrylamide (NIPAM).

PMID- 16602730
TI  - Blending chitosan with polycaprolactone: effects on physicochemical and
      antibacterial properties.
AB  - Chitosan is a well sought-after polysaccharide in biomedical applications and has
      been blended with various macromolecules to mitigate undesirable properties.
      However, the effects of blending on the unique antibacterial activity of chitosan
      as well as changes in fatigue and degradation properties are not well understood.
      The aim of this work was to evaluate the anti-bacterial properties and changes in
      physicochemical properties of chitosan upon blending with synthetic polyester
      poly(epsilon-caprolactone) (PCL). Chitosan and PCL were homogeneously dissolved
      in varying mass ratios in a unique 77% acetic acid in water mixture and processed
      into uniform membranes. When subjected to uniaxial cyclical loading in wet
      conditions, these membranes sustained 10 cycles of predetermined loads up to 1
      MPa without break. Chitosan was anti-adhesive to Gram-positive Streptococcus
      mutans and Gram-negative Actinobacillus actinomycetemcomitans bacteria. Presence
      of PCL compromised the antibacterial property of chitosan. Four-week degradation
      studies in PBS/lysozyme at 37 degrees C showed initial weight loss due to
      chitosan after which no significant changes were observed. Molecular interactions
      between chitosan and PCL were investigated using Fourier transform infrared
      spectroscopy (FTIR) which showed no chemical bond formations in the prepared
      blends. Investigation by wide-angle X-ray diffraction (WAXD) indicated that the
      crystal structure of individual polymers was unchanged in the blends. Dynamic
      mechanical and thermal analysis (DMTA) indicated that the crystallinity of PCL
      was suppressed and its storage modulus increased with the addition of chitosan.
      Analysis of surface topography by atomic force microscopy (AFM) showed a
      significant increase in roughness of all blends relative to chitosan. Observed
      differences in biological and anti-bacterial properties of blends could be
      primarily attributed to surface topographical changes.

PMID- 16602731
TI  - In vitro investigation on poly(lactide)-Tween 80 copolymer nanoparticles
      fabricated by dialysis method for chemotherapy.
AB  - Polysorbate 80 (Tween 80) has been widely used as an emulsifier with excellent
      effects in nanoparticles technology for biomedical applications. This work was
      thus triggered to synthesize poly(lactide)/Tween 80 copolymers with various
      copolymer blend ratio, which were synthesized by ring-opening polymerization and
      characterized by 1H NMR and TGA. Nanoparticles of poly(lactide)/Tween 80
      copolymers were prepared by the dialysis method without surfactants/emulsifiers
      involved. Paclitaxel was chosen as a prototype anticancer drug due to its
      excellent therapeutic effects against a wide spectrum of cancers. The drug-loaded
      nanoparticles of poly(lactide)/Tween 80 copolymers were then characterized by
      various state-of-the-art techniques, including laser light scattering for
      particles size and size distribution, field emission scanning electron microscopy
      (FESEM) and atomic force microscopy (AFM) for surface morphology; laser Doppler
      anemometry for zeta potential; differential scanning calorimetry (DSC) for the
      physical status of the drug encapsulated in the polymeric matrix; X-ray
      photoelectron spectrometer (XPS) for surface chemistry; high performance liquid
      chromatography (HPLC) for drug encapsulation efficiency; and in vitro drug
      release kinetics. HT-29 cells and Glioma C6 cells were used as an in vitro model
      of the GI barrier for oral chemotherapy and a brain cancer model to evaluate in
      vitro cytotoxicity of the paclitaxel-loaded nanoparticles. The viability of C6
      cells was decreased from 37.4 +/- 4.0% for poly(D,L-lactide-co-glycolic acid)
      (PLGA) nanoparticles to 17.8 +/- 4.2% for PLA-Tween 80-10 and 12.0 +/- 5.4% for
      PLA-Tween 80-20 copolymer nanoparticles, which was comparable with that for Taxol
      at the same 50 microg/mL drug concentration.

PMID- 16602732
TI  - Chemical and conformational study of the interactions involved in mycotoxin
      complexation with beta-D-glucans.
AB  - In a previous paper we reported that beta-D-glucans isolated from Saccharomyces
      cerevisiae could adsorb zearalenone, reduce its bioavailability in the digestive
      tract, and protect animals against its adverse effects. We have now investigated,
      in vitro, the kinetics of the interaction between other mycotoxins and beta-D
      glucans from several sources at three pH values found along the digestive tract
      (3.0, 6.0, and 8.0). Acid and neutral conditions gave the highest affinity rates
      for aflatoxins B1 > deoxynivalenol > ochratoxin A and involved both the (1 --> 3)
      beta-D-glucans and the (1 --> 6)-beta-D-glucans. Alkaline conditions, owing to
      their destructuring action on glucans, were favorable only for the adsorption of
      patulin. Using molecular mechanics, we found that hydroxyl, ketone, and lactone
      groups are involved in the formation of both hydrogen bonds and van der Waals
      interactions between aflatoxins B1, deoxynivalenol and patulin, and beta-D
      glucans. Differences in the binding capacity of the mycotoxins are due to their
      specific physical and chemical characteristics.

PMID- 16602733
TI  - Lectin-recognizable colloidal dispersions stabilized by n-dodecyl beta-D
      maltoside: particle-particle and particle-surface interactions.
AB  - Recently, we reported that it is possible to utilize sugars as stabilizing agents
      for colloidal particles. This study shows that when n-dodecyl beta-D-maltoside
      (DDM) is utilized as a dispersing and stabilizing agent in the synthesis and
      stabilization of poly[methyl methacrylate-co-(n-butyl acrylate)] (p-MMA/nBA)
      colloidal particles, stable colloidal dispersions can be formed. Since
      understanding of sugar-protein interactions have numerous practical and
      scientific implications, these studies examine DDM-stabilized p-MMA/nBA colloidal
      particles and their specific binding properties with concanavalin A (Con A). By
      use of spectroscopic analysis, unique binding characteristics that are a function
      of DDM concentration, time, and the concentration of Con A are detected. When DDM
      stabilized p-MMA/nBA particles are allowed to coalesce, DDM is released from the
      particle surfaces and, under suitable conditions, selectively stratifies in the
      areas of the excess of interfacial energy near the film-air (F-A) interface, thus
      providing sites for attracting Con A via alpha-glucose-OH hydrogen bonding.
      Consequently, adsorption of Con A at the F-A interfaces occur and the degree of
      adsorption is controlled by the amount of DDM at the F-A interface.

PMID- 16602734
TI  - Development of a low glycemic maize starch: preparation and characterization.
AB  - A low glycemic index starch was developed by partial alpha-amylase treatment, and
      its fine structure responsible for slowly digestible and resistant properties was
      investigated. Different digestion rates were obtained for gelatinized,
      retrograded starch by varying the enzyme dosage and reaction time. Analysis by
      high performance size-exclusion chromatography (HPSEC) coupled with multiangle
      laser-light scattering indicated that the molecular weighs of amylopectin and
      amylose were reduced during the digestion, to less than 100 kDa. A debranched
      chain length study using high performance anion-exchange chromatography equipped
      with an amyloglucosidase reactor and a pulsed amperometric detector and HPSEC
      revealed that short chains of amylopectin and noncrystalline amylose were rapidly
      digested, while DPn 121 chains showed resistance, followed by DPn 46 chains. X
      ray diffraction analysis revealed that the crystalline structure in the treated
      starches survived cooking. These starches not only have slowly digestible and
      resistant character, but also retain some branched structure for adequate
      functionality.

PMID- 16602735
TI  - Temperature-controlled properties of DNA complexes with poly(ethylenimine)-graft
      poly(N-isopropylacrylamide).
AB  - End-functionalized poly(N-isopropylacrylamide) (PNIPA) was synthesized by living
      free radical polymerization and conventional free radical polymerization and was
      used to prepare graft copolymers with poly(ethylenimine) (PEI). The copolymers
      exhibited lower critical solution temperature (LCST) behavior between 30 and 32
      degrees C and formed complexes with plasmid DNA. The LCST of the copolymers in
      the DNA complexes increased slightly to approximately 34-35 degrees C.
      Cytotoxicity of the copolymers was evaluated by measuring lactate dehydrogenase
      (LDH) release from cells. The copolymers exhibited temperature-dependent
      toxicity, with higher levels of LDH release observed at temperatures above the
      LCST. Cellular uptake and transfection activity of the DNA complexes with the PEI
      g-PNIPA copolymers were lower than those of the control PEI/DNA complexes at
      temperature below the LCST but increased to the PEI/DNA levels at temperatures
      above the LCST.

PMID- 16602736
TI  - Preparation of amphiphilic poly(L-lactide)-graft-chondroitin sulfate copolymer
      self-aggregates and its aggregation behavior.
AB  - Novel polymeric amphiphilic copolymers were synthesized using chondroitin sulfate
      (CS) as a hydrophilic segment and poly(L-lactide) (PLLA) as a hydrophobic
      segment. Micelles of those copolymers were formed in an aqueous phase and were
      characterized by 1H NMR spectra, fluorescence techniques, dynamic light
      scattering (DLS), atomic force microscopy (AFM), and confocal microscopy. Their
      critical aggregation concentrations (CAC) are in the range of 0.0043-0.0091 mg/mL
      at 25 degrees C. The partition equilibrium constants, Kv, of the pyrene probe in
      the aqueous solution were from 3.65 x 10(5) to 1.41 x 10(6) at 25 degrees C. The
      mean diameters of the micelles were below 200 nm, and their sizes were narrowly
      distributed. The AFM images revealed that the self-aggregates were spherical.
      Additionally, the CSn-PLLA micelles can efficiently transport within the cells
      via endocytosis as observed from confocal microscopy.

PMID- 16602738
TI  - Well-defined lactose-containing polymer grafted onto silica particles.
AB  - Reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-O
      meth-acryloyloxyethoxyl-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-4)
      2,3,6-tri-O-acetyl-beta-D-glucopyranoside (MAEL) was performed directly in CHCl3
      solutions using cumyl dithiobenzoate (CDB) as the chain transfer agent to give
      well-defined glycopolymers. The chemical composition and structure of the
      glycopolymer were characterized by 1HNMR, FTIR, and SEC. The living glycopolymer
      chains were subsequently grafted onto gamma-methacryloxypropyl-trimethoxy (MPTMS)
      modified silica particles. The acetyl groups of the poly(MAEL) grafted onto the
      silica gel particles were converted to the hydroxyl groups with CH3ONa/CH3OH,
      thus obtaining silica gel particles modified with well-defined lactose-carrying
      polymer.

PMID- 16602737
TI  - Refolding hydrogels self-assembled from N-(2-hydroxypropyl)methacrylamide graft
      copolymers by antiparallel coiled-coil formation.
AB  - A novel hybrid hydrogel system based on N-(2-hydroxypropyl)methacrylamide
      copolymers was proposed. It consisted of the hydrophilic polymer backbone and a
      pair of oppositely charged peptide grafts. Two distinct pentaheptad peptides (CCE
      and CCK) were anticipated to create a dimerization motif and serve as physical
      cross-linkers. Consequently, the graft copolymers CCE-P and CCK-P self-assembled
      into hybrid hydrogels in situ; the process was modulated by the formation of
      antiparallel heterodimeric coiled-coils. This approach possesses an advantage to
      decrease the steric hindrance of the polymer backbone on the "in-register"
      alignment of peptide grafts. Indeed, equimolar mixtures of the graft copolymers,
      CCE-P/CCK-P, have been observed to self-assemble into hydrogels in PBS solution
      at neutral pH at concentrations as low as 0.1 wt %. Circular dichroism
      spectroscopy, sedimentation equilibrium experiments, and microrheology revealed
      that the self-assembly process corresponded to the two-stranded alpha-helical
      coiled-coil formation between CCE and CCK. Moreover, the formation of hybrid
      hydrogels was reversible. Denaturation of the coiled-coil domains with guanidine
      hydrochloride (GdnHCl) solutions resulted in disassembly of the hydrogels.
      Removal of GdnHCl by dialysis caused coiled-coil refolding and hydrogel
      reassembly. Scanning electron microscopy results demonstrated that the
      concentration of the graft copolymers had a significant impact on the structure
      and morphology of self-assembled hydrogels.

PMID- 16602739
TI  - Chitosan-mediated synthesis of gold nanoparticles on patterned
      poly(dimethylsiloxane) surfaces.
AB  - Synthesis of gold nanoparticles on surfaces has been accomplished by the
      incubation of poly(dimethylsiloxane) (PDMS) films in tetrachloroauric(III) acid
      and chitosan solution at room temperature and 4 degrees C. One important point in
      the present study is that the synthesis selectively occurred on the PDMS surface.
      These observations are substantially different from the reaction in solution, in
      which no particles can be formed at room temperature. Computation of surface
      plasmon bands (SPBs) based on Mie theory suggests that the particles are
      partially coated by chitosan molecules, and the experimental results confirm the
      theoretical calculations. The proposed mechanism is that chitosan molecules
      adsorbed or printed on the PDMS surfaces act as reducing/stabilizing agents.
      Furthermore, PDMS films patterned with chitosan could induce localized synthesis
      of gold nanoparticles in regions capped with chitosan only. In this way,
      colloidal patterns were fabricated on the surfaces with high spatial selectivity
      simultaneously with the synthesis of the particles. Surface-induced fluorescence
      quenching was observed in the regions capped with gold nanoparticles as well.

PMID- 16602740
TI  - Solid-state NMR analysis of a peptide (Gly-Pro-Gly-Gly-Ala)6-Gly derived from a
      flagelliform silk sequence of Nephila clavipes.
AB  - Solid-state NMR is especially useful when the structures of peptides and proteins
      should be analyzed by taking into account the structural distribution, that is,
      the distribution of the torsion angle of the individual residue. In this study,
      two-dimensional spin-diffusion solid-state NMR spectra of 13C-double-labeled
      model peptides (GPGGA)6G of flagelliform silk were observed for studying the
      local structure in the solid state. The spin-diffusion NMR spectra calculated by
      assuming the torsion angles of the beta-spiral structure exclusively could not
      reproduce the observed spectra. In contrast, the spectra calculated by taking
      into account the statistical distribution of the torsion angles of the individual
      central residues in the sequences Ala-Gly-Pro, Gly-Pro-Gly, Pro-Gly-Gly, Gly-Gly
      Ala, and Gly-Ala-Gly from PDB data could reproduce the observed spectra well.
      This indicates that the statistical distribution of the torsion angles should be
      considered for the structural model of (GPGGA)6G similar to the case of the model
      peptide of elastin.

PMID- 16602741
TI  - Synthesis, physicochemical properties, and preliminary biological
      characterizations of a novel amphoteric agmatine-based poly(amidoamine) with RGD
      like repeating units.
AB  - A linear, amphoteric poly(amidoamine) nicknamed AGMA1, based on 4
      aminobutylguanidine, or agmatine, was successfully prepared by Michael-type
      polyaddition of monoprotonated agmatine and 2,2-bis(acrylamido)acetic acid (BAC).
      Copolymers between AGMA1 and the biocompatible poly(amidoamine) ISA23 (deriving
      from the polyaddition of 2-methylpiperazine with BAC) were also prepared. Acid
      base titrations gave for AGMA1 three acid dissociation constants, with pKa values
      of 2.25, 7.45, and >or=12.1, corresponding to a strong acid, a medium-weak base,
      and a strong base, respectively. The charge distribution profiles show that this
      polymer is prevailingly cationic at all physiological pH values, the positive net
      average charge per unit varying from about 0.5 at pH 7.4 to about 1.0 at pH 5,
      with an isoelectric point at pH approximately 10. Zeta-potential measurements
      confirmed this. Despite that, AGMA1 is nontoxic and nonhemolytic in vitro within
      all pH ranges tested (4-7.5). This is in contrast with the previously observed
      behavior of amphoteric PAAs, for instance ISA23, that are weakly hemolytic at pH
      7.4 but highly hemolytic at pH 5/5.5. The lack of hemolytic activity of AGMA1
      even at acidic pH values seems typical of the agmatine-BAC sequences and may be
      ascribed to their RGD-like structure. In fact, AGMA1-ISA23 copolymers behave in a
      way increasingly similar to that of ISA23; that is, they become hemolytic at low
      pH values as their ISA23 content increases.

PMID- 16602742
TI  - Synergistic interaction of xyloglucan and xanthan investigated by rheology,
      differential scanning calorimetry, and NMR.
AB  - A new synergistic interaction between tamarind seed xyloglucan and xanthan was
      found and investigated by rheology, differential scanning calorimetry (DSC), and
      NMR. The effect of the acetyl and pyruvate groups in the side chain in xanthan on
      the synergistic interaction was also examined. The shear moduli G' and G' ' of
      the mixture solution of xyloglucan and native (or acetate-free) xanthan increased
      steeply at around 22 degrees C upon cooling. An exothermic DSC peak appeared at
      the same temperature. A drastic decrease in the of the acetyl and pyruvate groups
      of the xanthan side chain was observed from 1H NMR spectra only in the mixture at
      low temperatures (<25 degrees C). It was found that the pyruvate group is more
      restricted in the mixture solution compared with the acetyl group. The mixture of
      xyloglucan and pyruvate-free xanthan showed no synergistic interaction. We
      concluded that this synergistic interaction is caused by the intermolecular
      binding between xyloglucan and xanthan, and, in the heterotypic junction zones,
      the xanthan side chain becomes a new state that is different from both the coil
      and helix states.

PMID- 16602743
TI  - Structural transformations during gelatinization of starches in limited water:
      combined wide- and small-angle X-ray scattering study.
AB  - Rice flour (18-25% moisture) and potato starch (20% moisture) were heated with
      continuous recording of the X-ray scattering during gelatinization. Rice flours
      displayed A-type crystallinity, which gradually decreased during gelatinization.
      The development of the characteristic 9 nm small-angle X-ray scattering (SAXS)
      peak during heating at sub-gelatinization temperatures indicated the gradual
      evolution into a stacked lamellar system. At higher temperatures, the crystalline
      and lamellar order was progressively lost. For potato starch (B-type
      crystallinity), no 9 nm SAXS peak was observed at ambient temperatures. Following
      the development of lamellar structures at sub-gelatinization temperatures, B-type
      crystallinity and lamellar order was lost during gelatinization. On cooling of
      partially gelatinized potato starch, A-type crystallinity steadily increased, but
      no formation of stacked lamellar structures was observed. Results were
      interpreted in terms of a high-temperature B- to A-type recrystallization, in
      which the lateral movement of double helices was accompanied by a shift along
      their helical axis. The latter is responsible for the inherent frustration of the
      lamellar stacks.

PMID- 16602744
TI  - Solid-phase supported polymer synthesis of sequence-defined, multifunctional
      poly(amidoamines).
AB  - A novel synthesis route toward multifunctional, sequence-defined polyamides is
      described. A fully automated, solid-phase supported polymer synthesis was
      developed and utilized to obtain linear poly(amidoamine) segments (PAAs) that
      exhibit the absence of molecular weight and chemical distribution. This was
      achieved by an alternating assembly of diacids and diamines, using a forced step
      growth mechanism, and driving each coupling step to completion. Within the
      monodisperse PAA segment, functionalities can be precisely positioned along the
      polymer chain allowing local control of the chain properties. The versatility of
      the approach was demonstrated by the conjugation of the monodisperse PAA segment
      toward an oligopeptide, leading to a single component block copolymer as verified
      by mass spectrometry. Moreover, two different poly(ethylene oxide)-PAA conjugates
      were synthesized utilizing the direct, solid-phase supported route. By varying
      the PAA repeat unit, the cationic nature of the PAA segment was adjusted,
      demonstrating the potential of the approach. The products were characterized by
      means of 1H NMR and matrix-assisted laser desorption mass spectrometry (MALDI-TOF
      MS) methods, which confirmed the chemical structures conclusively.

PMID- 16602745
TI  - Effect of molecular weight and ionic strength on the formation of polyelectrolyte
      complexes based on poly(methacrylic acid) and chitosan.
AB  - Chitosan/poly(methacrylic acid) complexes, CS/PMAA, were prepared via dropwise
      addition of a solution of PMAA to a solution of chitosan in acetic acid 2 wt %.
      The increase in molecular weight of PMAA inhibited the formation of insoluble
      complexes, while the increase in ionic strength first favored the formation of
      the complex followed by inhibiting it at higher concentrations. These
      observations were related to a description of polyelectrolyte complexation that
      was strongly dependent on macromolecular dimensions, both in terms of molecular
      weight and of coil expansion/contraction driven by polyelectrolyte effect.

PMID- 16602746
TI  - Synthesis and NMR characterization of new hyaluronan-based NO donors.
AB  - Nitric oxide (NO) and hyaluronic acid (HA), two species widely different in terms
      of molecular complexity and biological competence, are both known to play an
      important role in the wound healing process. To combine the properties of HA and
      NO, we synthesized new NO-donors based on hyaluronic acid derivatives exhibiting
      a controlled NO-release under physiological conditions (in vitro tests). Since
      two molecules of NO can form a covalent bond with secondary amines to yield
      structures, named NONO-ates, able to release NO in solution, we used spermidine
      bound to HA as the NO-linker. The HA-spermidine derivative was obtained by
      controlled HA amidation in aqueous media, activating the biopolymer carboxylate
      groups with a water soluble carbodiimide. The resulting derivative, soluble in
      water, was fully characterized by high field 1H and 13C NMR spectroscopy. The
      amount of grafting of spermidine on HA was determined by integration of suitable
      1H NMR signals. In addition, cross-linked derivatives of HA were synthesized by
      the Ugi's four-component reaction using formaldehyde, cyclohexylisocyanide, and
      spermidine. The HA-spermidine networks were characterized by 13C CP-MAS NMR
      spectroscopy. The degree of cross-linking of the networks was also determined.
      Finally, the release of NO from the swollen hydrogels freshly saturated with NO,
      in contact with aqueous media, was monitored by means of UV spectrophotometric
      measurements.

PMID- 16602748
TI  - Solid state NMR investigation of the molecular dynamics of cocoon silks produced
      by different Bombyx mori (Lepidoptera) strains.
AB  - Cocoons produced by different strains of Bombyx mori larvae were investigated by
      a combination of several high- and low-resolution 1H and 13C solid-state NMR
      techniques in order to characterize and compare their dynamic behavior at a
      molecular level. A detailed interpretation in terms of molecular motions in these
      very complex systems was possible thanks to the integrated analysis of different
      relaxation measurements and high-resolution selective experiments. Untreated
      cocoons of all strains were found to be mainly constituted by two different types
      of rigid domains and by a third one, more mobile, due to physisorbed water
      molecules. Dynamic processes in the MHz and kHz ranges were characterized by
      means of different 1H and 13C relaxation times. Cocoons arising from different
      strains exhibit a different content of physisorbed water and also slightly
      different dynamic behavior, especially in the MHz regime.

PMID- 16602747
TI  - Peptide-based biomaterials for protease-enhanced drug delivery.
AB  - Controlled delivery of drugs in response to environments has the potential of
      targeting therapies and personalized treatments. Here, we described self
      assembled peptide sequences that release therapeutic payloads upon specific
      interaction with disease-associated proteases. The core peptide sequence consists
      of a protease cleavable region flanked by two self-assembly motifs. In aqueous
      solution, the peptides self-assemble as a gel scaffold. With treatment of the
      model preparations with the appropriate protease, the matrix can be degraded in a
      controlled fashion, where the degradation rate is fine-tuned by varying the
      peptide compositions. Protease-mediated drug release was demonstrated by
      enzymatic treatment of a model therapeutic peptide incorporated into the
      optimized matrix. Our results suggest that this type of material may have far
      reaching applications for functionally targeted drug delivery.

PMID- 16602749
TI  - Enhancement of transcriptional activity of DNA complexes by amphoteric PEG
      derivative.
AB  - A water-soluble PEG derivative having both amino and carboxylic acid side chains
      (PEG-AC) was synthesized and explored for its transcription- and transfection
      enhancing activity. PEG-AC could be deposited onto the surface of DNA/polycation
      complexes to form a ternary complex with slightly negative surface potential. PEG
      AC-coating on the plasmid/PEI complexes obviously enhanced their transcriptional
      activity, and 31-fold higher consumption of UTP was observed. Amphoteric PEG-AC
      would loosen the tightly compacted DNA/PEI complex and facilitate the approach of
      transcriptional factors. PEG-AC also evidently improved the transgene expression
      level on the cultured CHO cells.

PMID- 16602750
TI  - Electrically conductive bacterial cellulose by incorporation of carbon nanotubes.
AB  - Electrically conducting polymeric membranes were prepared by incorporating
      multiwalled carbon nanotubes (MWCNTs) into bacterial cellulose pellicles produced
      by Gluconacetobacter xylinum. The MWCNTs were dispersed in a surfactant (cationic
      cetyl trimethylammonium bromide) solution, and cellulose pellicles were dipped
      into the solution for 6, 12, and 24 h. The surfactants were then extracted in
      pure water and dried. Electron microscopy showed that the individual MWCNTs were
      strongly adhered to the surface and the inside of the cellulose pellicle. The
      conductivity of the MWCNTs-incorporated cellulose pellicle, as measured by a four
      probe at room temperature, was 1.4 x 10(-1) S/cm, based on the total cross
      sectional area (approximately 9.6 wt % of MWCNTs). This suggests that the MWCNTs
      were incorporated uniformly and densely into the pellicles.

PMID- 16602751
TI  - pH dependence and protein selectivity of poly(ethyleneimine)/poly(acrylic acid)
      multilayers studied by in situ ATR-FTIR spectroscopy.
AB  - The selective interaction between polyelectrolyte multilayers (PEM) consecutively
      adsorbed from poly(ethyleneimine) (PEI) and poly(acrylic acid) (PAC) and a binary
      mixture containing concanavalin A (COA) and lysozyme (LYZ) based on electrostatic
      interaction is reported. The composition and structure of the PEM and the uptake
      of proteins were analyzed by in situ attenuated total reflection (ATR) Fourier
      transform infrared (FTIR) spectroscopy, and the morphology and thickness were
      characterized by atomic force microscopy (AFM) and ellipsometry. The PEM
      dissociation degree and charge state and the protein adsorption were shown to be
      highly dependent on the outermost layer type and the pH in solution. High protein
      uptake was obtained under electrostatically attractive conditions. This was used
      to bind selectively one protein from a binary mixture of LYZ/COA. In detail it
      could be demonstrated that six-layered PEM-6 at pH = 7.3 showed a preferential
      sorption of positively charged LYZ, while at PEM-5 and pH = 7.3 negatively
      charged COA could be selectively bound. No protein sorption from the binary
      mixture was observed at pH = 4.0 for both PEM, when COA, LYZ, and the outermost
      PEI layer of PEM-5 were positively charged or the outermost PAC layer of PEM-6
      was neutral. Furthermore, from factor analysis of the spectral data the higher
      selectivity was found for PEM-5 compared to PEM-6. Increasing the ionic strength
      revealed a drastic decrease in the selectivity of both PEM. Evidence was found
      that the proteins were predominantly bound at the surface and to a minor extent
      in the bulk phase of PEM. These results suggest possible working regimes and
      application fields of PEI/PAC multilayer assemblies related to the preparative
      separation of binary and multicomponent protein mixtures (biofluids, food) as
      well as to the design of selective protein-resistant surfaces.

PMID- 16602752
TI  - Interaction and comparison of a class I hydrophobin from Schizophyllum commune
      and class II hydrophobins from Trichoderma reesei.
AB  - Hydrophobins fulfill a wide spectrum of functions in fungal growth and
      development. These proteins self-assemble at hydrophilic-hydrophobic interfaces
      into amphipathic membranes. Hydrophobins are divided into two classes based on
      their hydropathy patterns and solubility. We show here that the properties of the
      class II hydrophobins HFBI and HFBII of Trichoderma reesei differ from those of
      the class I hydrophobin SC3 of Schizophyllum commune. In contrast to SC3, self
      assembly of HFBI and HFBII at the water-air interface was neither accompanied by
      a change in secondary structure nor by a change in ultrastructure. Moreover,
      maximal lowering of the water surface tension was obtained instantly or took
      several minutes in the case of HFBII and HFBI, respectively. In contrast, it took
      several hours in the case of SC3. Oil emulsions prepared with HFBI and SC3 were
      more stable than those of HFBII, and HFBI and SC3 also interacted more strongly
      with the hydrophobic Teflon surface making it wettable. Yet, the HFBI coating did
      not resist treatment with hot detergent, while that of SC3 remained unaffected.
      Interaction of all the hydrophobins with Teflon was accompanied with a change in
      the circular dichroism spectra, indicating the formation of an alpha-helical
      structure. HFBI and HFBII did not affect self-assembly of the class I hydrophobin
      SC3 of S. commune and vice versa. However, precipitation of SC3 was reduced by
      the class II hydrophobins, indicating interaction between the assemblies of both
      classes of hydrophobins.

PMID- 16602753
TI  - Photo-cross-linked hydrogels with polysaccharide-poly(amino acid) structure: new
      biomaterials for pharmaceutical applications.
AB  - The aim of this work has been the preparation and characterization of novel
      hydrogels with polysaccharide-poly(amino acid) structure having suitable
      physicochemical properties for pharmaceutical applications. In the first step,
      hyaluronic acid (HA) and alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA)
      have been derivatized with methacrylic anhydride (AMA), thus obtaining HA-AMA and
      PHM derivatives, respectively. In the second step, aqueous solutions of both
      these derivatives have been irradiated at 313 nm to obtain chemical hydrogels.
      The hydrogel obtained by irradiating for 15 min an aqueous solution containing 4%
      w/v of HA-AMA and 4% w/v of PHM resulted in the highest yield. Its swelling
      ability was dependent on the pH and nature of the external medium. Besides, this
      hydrogel undergoes a partial hydrolysis, especially in the presence of enzymes,
      such as esterase or hyaluronidase, but the entity of this degradation is lower
      than that observed for a hydrogel based on HA-AMA alone. The ability of this
      hydrogel to entrap drug molecules has been evaluated by using thrombin as a model
      drug. In vitro release studies and a platelet aggregation test demonstrated that
      the HA-AMA/PHM hydrogel is able to release thrombin in the active form, thus
      suggesting its suitability for the treatment of hemorrhages.

PMID- 16602754
TI  - Characterization of aggregate structure in mercerized cellulose/LiCl.DMAc
      solution using light scattering and rheological measurements.
AB  - The structure of a semidilute solution of mercerized cellulose (CC1m) in 8% (w/w)
      LiCl.DMAc, which contained some aggregates, was investigated using static and
      dynamic light scattering measurements. The static scattering function of the
      polymer solution containing a small amount of aggregates can be separated into
      fast- and slow-mode components by combining static and dynamic light scattering
      measurements. The osmotic modulus was identical for the fast-mode component of
      the CC1m solutions and the native cellulose (CC1) solutions, in which cellulose
      is dispersed molecularly. This indicates that the molecularly dispersed component
      of the CC1m solutions has an identical conformation with the cellulose molecules
      in the CC1 solutions. The correlation length was also identical for the fast-mode
      components of CC1m solutions and the CC1 solutions, indicating that these
      solutions have the same mesh size of the polymer entanglement. These observations
      for the fast-mode components are consistent with the concentration dependence of
      the zero shear rate viscosity and the plateau modulus estimated in the
      rheological measurements. The slow-mode component, on the other hand, gave
      information on the aggregate structure in the CC1m solution. The radius of
      gyration of the aggregate structure estimated from the slow-mode component was
      about 70 nm, which is independent of the concentration of the solution. The plots
      for particle scattering factor of the slow-mode component lay between the
      theoretical curve of a sphere and a Gaussian chain, implying that the structure
      of the aggregate in the CC1m solution is like a multiarm polymer. A
      characteristic time of the slow-mode component calculated with the translational
      diffusion coefficient and the radius of gyration were almost identical with the
      relaxation time of the long-time relaxation observed in the rheological
      measurements. This indicates that the long-time relaxation of CC1m solutions
      originates in the translational diffusion of the aggregate structure in the
      solution.

PMID- 16602755
TI  - Glycine derived polymerizable cosurfactant in the synthesis of functionalized
      poly(butyl acrylate) nanolatexes.
AB  - The approach of employing N-glycinylmaleamic acid (NGMA) as an efficient
      cosurfactant to provide microemulsion polymerization of butyl acrylate using a
      weight ratio of sodium dodecyl sulfate (SDS)/butyl acrylate (BA) at <or=1.5,
      which is lower than that employed in previous experiments, has been demonstrated.
      The narrow polydispersity index at 1.36-1.48 of poly(butyl acrylate) copolymers
      from investigated microemulsion polymerization reactions evidences the promotion
      of a controlled polymerization reaction, in contrast to the solution
      polymerization method generating polymers with higher polydispersity index at
      3.15-4.23. The enhanced incorporation of NGMA at approximately 0.35 m in the
      copolymer demonstrates the merits of the proximity effect enabled in the
      microemulsion polymerization reaction. The incorporation of NGMA promotes
      rigidity of the polymer chain as suggested by a higher Tg of -16.8 degrees C for
      the copolymer in comparison to that of the poly(butyl acrylate) homopolymer.

PMID- 16602756
TI  - Diffusional behavior of poly(beta-benzyl L-aspartate) in the rodlike, random
      coil, and intermediate forms as studied by high field-gradient 1H NMR
      spectroscopy.
AB  - The diffusion coefficients of poly(beta-benzyl L-aspartate)(PBLA) with the alpha
      helix (rodlike) form in chloroform and the random-coil form in a mixture of
      chloroform and trifluoroacetic acid have been measured as a function of the PBLA
      concentration (C(PBLA)) by using high field-gradient 1H NMR. The PBLA
      concentration range for the former is from 0.11 to 9.20 wt % and for the latter
      it is from 0.20 to 25.2 wt %. From these experimental results, it is found that
      the diffusion coefficient of PBLA in the rodlike form is much smaller than that
      of PBLA in the random-coil form at the same PBLA concentration. This implies that
      the small diffusion coefficients of PBLA in the rodlike form as compared with
      those in the random-coil form come from the relatively large radius of gyration
      Rg. Further, it is found that the diffusional behavior of PBLA in the rodlike
      form is different in the three PBLA concentration regions, that is, region 1
      (C(PBLA) = 0.11 approximately 0.39 wt %), region 2 (C(PBLA) = 0.39 approximately
      0.86 wt %), and region 3 (C(PBLA) = 0.86 approximately 9.20 wt %). In the random
      coil form, the diffusion is different in the two PBLA concentration regions, that
      is, region I (C(PBLA) = 0.20 approximately 1.03 wt %) and region II (C(PBLA) =
      1.03 approximately 25.2 wt %). These diffusional behaviors in the rodlike form
      and in the random-coil form can be reasonably explained by Tinland-Maret-Rinaudo
      theory and de Gennes theory, respectively. Further, transitional change from the
      rodlike form to the random-coil form is discussed on the basis of the diffusional
      behavior.

PMID- 16602757
TI  - Self-assembly, antipolyelectrolyte effect, and nonbiofouling properties of
      polyzwitterions.
AB  - An explanation of the unique nonbiofouling properties of polyzwitterions (PZ) is
      proposed [in this paper, the term "polyzwitterion" is preferred to "polybetain"].
      The existence of an osmotic component of the driving force of the
      antipolyelectrolyte effect (APE) and the parameters governing this phenomenon are
      quantitatively established. The correlation between this effect, which is
      specific of PZ only, and the PZ nonbiofouling properties is grounded.

PMID- 16602759
TI  - Biosynthesis and characterization of deuterated polyhydroxyoctanoate.
AB  - The synthesis of a polyhydroxyalkanoate with medium chain length alkyl
      substituents by Pseudomonas oleovoranswas investigated using protonated and
      deuterated forms of octanoic acid in a minimal salts medium. Cultivation with
      deuterated octanoic acid resulted in a reduced rate of polymer accumulation
      compared to that with its protonated counterpart (107 and 207 mg of polymer L(-1)
      of medium h(-1) of cultivation, respectively). Nuclear magnetic resonance and gas
      chromatography coupled mass spectrometry of the derivatized polymer was used to
      establish the extent and distribution of deuterium in the biopolymer. A partially
      deuterated heteropolymer with 3-hydroxyoctanoic acid as the main constituent was
      produced. Deuteration is an important tool for contrast variation studies using
      neutron scattering, but predicates that the deuterated polymer is otherwise
      comparable in its physiochemical and material properties to its protonated
      counterpart. In studies reported here, the deuterated biopolymer exhibited an
      additional diffraction maximum at 7.55 A and slight differences in its melting
      point (60 and 55 degrees C) and glass transition temperature (-39 and -36 degrees
      C) when compared to its protonated equivalent. While significant differences
      between the protonated and deuterated biopolymers were determined, our results
      support the use of this deuterated polyhydroxyalkanoate in its application in
      investigations using analytical neutron scattering techniques.

PMID- 16602760
TI  - Effect of albumin conformation on the binding of ciprofloxacin to human serum
      albumin: a novel approach directly assigning binding site.
AB  - Human serum albumin (HSA) is known to exist as N (pH approximately 7), B (pH
      approximately 9), and F (pH approximately 3.5) isomeric forms and an equilibrium
      intermediate state (I) accumulate in the urea induced unfolding pathway of HSA
      around 4.8-5.2 M urea concentrations. These states displayed characteristic
      structure and functions. To elucidate the ciprofloxacin (CFX) binding behavior of
      HSA, the binding of ciprofloxacin with these conformational states of human serum
      albumin (HSA) has been investigated by fluorescence spectroscopy. The binding
      constant (K) for N, B, F, and I conformation of HSA were 6.92 x 10(5), 3.87 x
      10(5), 4.06 x 10(5), and 2.7 x 10(5) M(-1) and the number of binding sites (n)
      were 1.26,1.21, 1.16, and 1.19, respectively. The standard free energy changes
      (DeltaGbinding(0)) of interaction were found to be -33.3 (N isomer), -31.8 (B
      isomer), -32 (F isomer), and -30.0 kJ mol(-1) respectively. By using unfolding
      pathway of HSA, domain II of HSA has been assigned to possess binding site of
      ciprofloxacin. Plausible correlation between stability of CFX-N and CFX-B
      complexes and drug distribution have been discussed. At plasma concentration of
      HSA fraction of free CFX, which contributes potential to its rate of transport
      across cell membrane, was found to be approximately 80% more for B isomers
      compared to N isomers of HSA. The conformational changes in two physiologically
      important isomers of HSA (N and B isomers) upon ciprofloxacin binding were
      evaluated by measuring far, near-UV CD, and fluorescence properties of the CFX
      HSA complex.

PMID- 16602758
TI  - Delivery of sphingosine 1-phosphate from poly(ethylene glycol) hydrogels.
AB  - While protein growth factors promote therapeutic angiogenesis, delivery of lipid
      factors such as sphingosine 1-phosphate (S1P) may provide better stabilization of
      newly formed vessels. We developed a biomaterial for the controlled delivery of
      S1P, a bioactive lipid released from activated platelets. Multiarm poly(ethylene
      glycol)-vinyl sulfone was cross-linked with albumin, a lipid-transporting
      protein, to form hydrogels. The rate of S1P release from the materials followed
      Fickian kinetics and was dependent upon the presence of lipid carriers in the
      release solution. Delivery of S1P from RGD-modified hydrogels increased the cell
      migration speed of endothelial cells growing on the materials. The materials also
      induced angiogenesis in the chorioallantoic membrane assay. Our data demonstrate
      that the storage and release of lipid factors provides a new route for the
      induction of angiogenesis by artificial materials.

PMID- 16602761
TI  - Adsorption behavior of bovine serum albumin on lowly activated anionic exchangers
      suggests a new strategy for solid-phase proteomics.
AB  - Diluted solutions of bovine serum albumin (BSA) (e.g., 0.1 mg /mL) do not form
      detectable protein large aggregates. Using gel-filtration experiments, we
      determined that a diluted solution of BSA is 97% monomeric BSA and 3% dimeric.
      The adsorption of this diluted BSA on highly activated anionic exchangers (e,g.,
      having 40 micromol/wet g) keeps this mainly monomeric form. When supports
      activated with 2 micromol/wet g are used, only dimers become adsorbed to the
      support, accounting for 100% of the offered BSA. When the diluted BSA solution is
      offered to very mildly activated anionic exchangers (even only 0.125 micromol/wet
      g), an unexpected adsorption of most of the BSA on the support was also observed.
      These very slightly activated supports are only able to adsorb very large
      proteins or very large protein-protein complexes, larger than BSA dimers. In
      fact, a rapid cross-linking of the adsorbed BSA with dextran-aldehyde reveals the
      formation of very large BSA-BSA complexes with molecular mass higher than 500 000
      Da, complexes that may be observed for soluble BSA with very high concentrations
      but are not detectable at 0.1 mg/mL. Moreover, the size of the aggregates
      strongly depends on the concentration of the ionized groups on the support: the
      less activated the supports are, the higher the sizes of the complexes. It seems
      that the interaction of the BSA molecules on the margins of the BSA aggregate
      with the groups on the support may stabilize the whole protein aggregate,
      although some components are not interacting with the support. Aggregates could
      account for more than 40% of the BSA in the solution after 50 h of incubation.
      However, only these large BSA aggregates were adsorbed in the support.

PMID- 16602762
TI  - Biodegradable polylactide/chitosan blend membranes.
AB  - Biodegradable blend membranes based on polylactide and chitosan with various
      compositions were prepared via a two-step processing pathway. In the first step,
      solutions of each component were properly mixed and cast into a gelatinous
      membrane, and in the second step, the obtained membrane was immersed into a mixed
      solution for the solvent extraction followed by a drying procedure to finally
      generate a well-blended membrane. An acetic acid-acetone solvent system was
      selected for poly(DL-lactide)/chitosan membranes, and another solvent system for
      poly(L-lactide)/chitosan membranes consisted of acetic acid and dimethyl
      sulfoxide. Some processing parameters, such as the concentration of component
      solutions and the composition ratio of mixed solvents and extraction solvents,
      were optimized by primarily considering whether the directly visible phase
      separation occurred during the processing procedures. Morphologies of these blend
      membranes were viewed using SEM. It was found that the processing parameters
      exerted quite notable impacts on the morphology of the membranes. The
      hydrophilicity of membranes was examined by measuring their water contact angle
      and swelling index. These blend membranes were also investigated for their
      miscibility using IR spectra, X-ray diffractograms, TG, DSC, and dynamic
      mechanical analysis methods. Although the presence of phase separation at a
      microscopic level was detected for these membranes, pronounced interactions
      between components were confirmed. The obtained results shown that some membranes
      prepared under optimized processing conditions had a partially miscible
      structure.

PMID- 16602763
TI  - Synthesis of polyester-polypeptide diblock and triblock copolymers using amino
      poly(epsilon-caprolactone) macroinitiators.

PMID- 16602764
TI  - Ratiometric Zn2+ sensor and strategy for Hg2+ selective recognition by central
      metal ion replacement.
AB  - Strategies of both self-assembly and metal ion replacement were adopted in the
      development of new metal ion sensors for Zn2+ and Hg2+. Ligand BPBA, phenylene
      bridged bis(pyrrol-2-ylmethyleneamine), could self-assemble to form a molecular
      square in the presence of Zn2+, which showed strong emission in solution. The
      fluorescent emission of formed BPBA-Zn2+ dropped with the addition of Hg2+. BPBA
      could be a good Zn2+ sensor candidate and BPBA-Zn2+ could be a good Hg2+ sensor
      candidate based on the mechanisms of the chelation-enhanced fluorescence effect
      and the replacement of central metal ion induced chelation-enhanced fluorescence
      quenching effect, respectively.

PMID- 16602765
TI  - [NaCu(II)4] cluster from alkali template assembly of two asymmetric end-on azido
      bridged [Cu(II)2] units.
AB  - The cluster [NaCu4L2(N3)2](ClO4) [1; H3L is 2-(2'-hydroxyphenyl)-1,3-bis[3'-aza
      4'-(2''-hydroxyphenyl)prop-4'-en-1'-yl]-1,3-imidazolidine] has been synthesized
      and structurally characterized. Complex 1 is formed by the template assembly of
      two [Cu2L(N3)] neutral fragments through their weak oxophilic interactions with a
      central Na+ cation as observed in metallacrowns. The cluster exhibits a
      combination of ferro- and antiferromagnetic interactions. End-on N3- bridging of
      copper ions within the [Cu(II)2] units facilitates stabilization of S = 1
      magnetic subunits that mutually cancel via antiferromagnetic coupling as mediated
      by the O...Na+...O bridges.

PMID- 16602766
TI  - Synthesis, structural characterization, and theoretical studies of complexes of
      magnesium and calcium with gallium heterocycles.
AB  - The magnesium- and calcium-gallium heterocycle complexes
      [Mg{Ga[(ArNCH)2]}2(THF)3] and [Ca{Ga[(ArNCR)2]}2(THF)4], R = H or Me, Ar =
      C6H3Pr(i)2-2,6, have been prepared via the reduction of [I2Ga{(ArNCR)2}] with the
      group 2 metal in tetrahydrofuran. The mechanisms of the reactions have been
      elucidated, and the crystal structures of the complexes exhibit the first
      structurally authenticated Ga-Mg and Ga-Ca bonds in molecular species.
      Theoretical studies suggest that the heterocycle-group 2 metal interactions have
      significant ionic character.

PMID- 16602767
TI  - Syntheses, crystal structures, and properties of heterometallic iodoplumbates:
      bicubane, ribbon, and chain configurations.
AB  - Successful introduction of Cu/Ag cations into the Pb/I system has led to the
      formation of four unprecedented heterometallic iodoplumbates in which the common
      connection of PbI6 units has been remarkably altered. Also, interesting long
      lived fluorescence properties have been found.

PMID- 16602768
TI  - One-dimensional mu-chloromanganese(II)-tetrathiafulvalene (TTF) coordination
      compound.
AB  - A new tetrathiafulvalene derivative 1 bearing a single pyridine group and its
      coordination complex 2, with stoichiometry [Mn(mu-Cl)Cl(1)2(CH3OH)]n, have been
      synthesized and fully characterized. The complex 2 shows an extended chain
      structure, which is potentially favorable for electrical conductivity. Notably,
      this is the first monohalogen-bridged Mn(II) polymer exhibiting a moderate
      antiferromagnetic coupling between the Mn(II) centers.

PMID- 16602769
TI  - Highly efficient, selective, and general method for the preparation of meridional
      homo- and heteroleptic tris-cyclometalated iridium complexes.
AB  - A highly efficient and general method based on transmetalation with an organozinc
      reagent is developed for selective preparation of homo- and heteroleptic
      meridional tris-cyclometalated iridium complexes. The molecular structure of mer
      Ir(1-piq)2(ppy) (2) has been determined by a single-crystal X-ray diffraction
      analysis. The emission properties of a series of meridional complexes are
      reported.

PMID- 16602770
TI  - Dual emission from luminescent nonalanthanide clusters.
AB  - Clusters containing nine lanthanide and six sodium ions are crystallized with the
      help of a tridentate ligand bearing a phosphonic acid group; the structure of the
      Eu(III) compound reveals a host-guest assembly Eu [symbol: see text] Na6Eu8L16
      with a substantial quantum yield (32%). A similar Eu(III)-Yb(III) structure
      displays dual luminescence in the visible (Eu(III)) and NIR (Yb(III)) ranges.

PMID- 16602771
TI  - A polar luminescent Zn polymer containing an unusual noninterpenetrated utp net.
AB  - A new Zn coordination polymer with the mixed ligands of 1,3,5
      benzenetricarboxylate and 1,3-bis(4-pyridyl)propane has been hydrothermally
      synthesized, and an unusual distorted noninterpenetrated utp [or (10,3)-d] net
      has been defined.

PMID- 16602773
TI  - Adventures with substances containing metals in negative oxidation states.
AB  - A brief history of substances containing s,p- and d-block metals in negative
      oxidation states is described. A classification of these species and discussions
      of formal oxidation state assignments for low-valent transition metals in
      complexes are included, along with comments on the innocent and noninnocent
      character of ligands in metalates. Syntheses of highly reduced carbonyl complexes
      formally containing transition metals in their lowest known oxidation states of
      III- and IV- are discussed. Atmospheric-pressure syntheses of early-transition
      metal carbonyls involving alkali-metal polyarene-mediated reductions of non
      carbonyl precursors have been developed. In the absence of carbon monoxide, these
      reactions afford homoleptic polyarenemetalates, including the initial species
      containing three aromatic hydrocarbons bound to one metal. In several instances,
      these metalates function as useful synthons for "naked" spin-paired atomic anions
      of transition metals.

PMID- 16602772
TI  - Catalytic reduction of hydrazine to ammonia by a vanadium thiolate complex.
AB  - Vanadium(III) thiolate complexes, [V(PS3'')(Cl)]- [1a; PS3'' = P(C6H3-3-Me3Si-2
      S)3(3-)] and [V(PS3')(Cl)]- [1b; PS3' = P(C6H3-5-Me-2-S)3(3-)], were synthesized
      and characterized. Complex 1a serves as a precursor for the catalytic reduction
      of hydrazine to ammonia. The spectroscopic and electrochemical studies indicate
      that hydrazine is bound and activated in a V(II) state.

PMID- 16602774
TI  - Characterization of a bimetallic-bridging intermediate in the reduction of NO to
      N2O: a density functional theory study.
AB  - We have applied density functional theory to characterize the bimetallic-bridging
      intermediate in the reduction of NO to N2O by heme-copper oxidoreductases. The
      present study provides information of the electronic and vibrational structure of
      the putative intermediate, and thus, it forms the basis for a quantitative
      accurate atomic-level description of the key steps in the N-N bond formation and
      the N-O bond cleavage mechanism.

PMID- 16602775
TI  - Structural and spectroscopic characterization of copper(II) complexes of a new
      bisamide functionalized imidazole tripod and evidence for the formation of a
      mononuclear end-on Cu-OOH species.
AB  - A new polyimidazole tripod N,N-bis((1-methyl-4-pivalamidoimidazol-2-yl)methyl)-N'
      ((1-methylimidazol-2-yl)methyl)amine (L2) has been synthesized and shown to form
      intramolecular hydrogen bonds with different axial ligands bonded to Cu(II) in
      the solid state. The same hydrogen-bonding property of L2 appears responsible for
      the stabilization of a Cu(II)-OOH species in solution. The crystal structures of
      L2 and three of its Cu(II) complexes are reported. The [Cu(L2)X]ClO4 complexes, 4
      6 (X- = Cl-, OH-, or N3-) have distorted trigonal bipyramidal geometries in the
      solid state and have been characterized further by UV-vis absorption, electron
      paramagnetic resonance (EPR) spectroscopy, and cyclic voltammetry. The reaction
      of [Cu(L2)OH](ClO4) (5) with H2O2 and tert-butyl hydroperoxide in methanol
      generates [Cu(L2)OOH](ClO4) (7) and [Cu(L2)OO(t)Bu](ClO4) (8) which have been
      characterized by different spectroscopic methods. The compound [Cu(L2)OO(t)Bu]+
      displays a band at 395 nm (epsilon = 950 M(-1) cm(-1)) assigned to an alkylperoxo
      pi*(sigma) --> Cu ligand-to-metal charge transfer (LMCT) transition, while
      [Cu(L2)OOH]+ displays a peroxo pi*(sigma) --> Cu charge-transfer transition at
      365 nm with epsilon = 1300 M(-1) cm(-1), a mass ion at m/z 593.4, and nu(O-O)
      stretch (resonance Raman) at 854 cm(-1) that shifts to lower energy by 46 cm(-1)
      upon 18O substitution.

PMID- 16602776
TI  - Trisilane-1,3-diolato complexes of Ti and Zr: syntheses and X-ray crystal
      structures.
AB  - The syntheses and structures of zirconium and titanium complexes containing the
      novel chelating trisilane-1,3-diolate ligand [Me2Si(R2SiO)2]2- (R = SiMe3) (5)-H2
      are reported. The chloride complexes [Me2Si(R2SiO)2]TiCl2 (7a) and
      [Me2Si(R2SiO)2]ZrCl2 x 2 THF (7b) were prepared by the reaction of MCl4 (M = Ti,
      Zr) with [Me2Si(R2SiO)2]2Ti (6a) and [Me2Si(R2SiO)2]2Zr (6b), which are derived
      from the reaction of 5 with M(NEt2)4, respectively. In the presence of TiCl4,
      complexes 6a and 7a undergo a ring-opening reaction to produce the dinuclear
      complex [Me2Si(R2SiO)2][TiCl3]2 (9). [Me2Si(R2SiO)2]TiMe2 (10) and
      [Me2Si(R2SiO)2]TiBnz2 (11) were prepared in moderate yields from reactions of 7a
      with 2 equiv of MeMgBr and BnzMgCl, respectively. According to NMR spectroscopic
      investigations, the reaction of the dimethyltitanium complex 10 with B(C6F5)3 led
      to full exchange of both methyl groups by C6F5 groups under quantitative
      formation of [Me2Si(R2SiO)2]Ti(C6F5)2 (12) and a mixture of B(C6F5)(3-n)Me(n),
      where n = 1-3. The structure of 12 is further evidenced by the preparation of an
      identical sample from the reaction of 7a with 2 equiv of C6F5MgBr. Refluxing an
      ether solution of 12 surprisingly gave [Me2Si(R2SiO)2]2TiC6F5]2O (13) as a result
      of ether cleavage. The structures of the complexes 7a, 7b, 9, 10, and 13 were
      determined by X-ray crystallography, and structural discussion of the bond
      parameters will be given.

PMID- 16602777
TI  - Correlated ab initio study of the excited state of the iron-coordinated-mode
      noninnocent glyoxalbis(mercaptoanil) ligand.
AB  - The intriguing and theoretically unresolved magnetic coupling in the Fe(gma)CN
      (1) compound [gma = glyoxalbis(mercaptoanil)] has been investigated by means of
      first-principle correlated ab initio calculations. The low-energy spectrum of the
      complex has been studied using the difference dedicated configuration interaction
      method, which is a dynamically correlated multiconfigurational method. In
      agreement with available spectroscopic information, we found that the ground
      state doublet is dominated by the coupling between an iron-centered quartet and
      the first excited triplet on the gma ligand. The open-shell character of the
      electronic structure of the ligand clarifies its noninnocent nature. The low
      energy spectrum reveals the presence of a first excited quartet of different
      symmetry lying 200 cm(-1) above. The lowest excitation energy in the ground-state
      symmetry is found at 4790 cm(-1), thus ruling out the simple description of the
      system based on a Heisenberg Hamiltonian.

PMID- 16602778
TI  - Crystal structure and ionic conductivity of three polymorphic phases of rubidium
      trifluoromethyl sulfonate, RbSO3CF3.
AB  - The crystal structures of three polymorphic phases of rubidium trifluoromethyl
      sulfonate (RbSO3CF3, rubidium 'triflate') were solved from X-ray powder
      diffraction data. At room temperature, rubidium triflate crystallizes in the
      monoclinic space group Cm with lattice parameters of a = 19.9611(5) A, b =
      23.4913(7) A, c = 5.1514(2) A, beta = 102.758(2) degrees; Z = 16. At T = 321 K, a
      first-order phase transition occurs toward a monoclinic phase in space group
      P2(1) with lattice parameters at T = 344 K of a = 10.3434(5) A, b = 5.8283(3) A,
      c = 5.1982(3) A, beta = 104.278(6) degrees; Z = 2). At T = 461 K, another phase
      transition, this time of second order, occurs toward an orthorhombic phase in
      space group Cmcm with lattice parameters at T = 510 K of a = 5.3069(2) A, b =
      20.2423(10) A, c = 5.9479(2) A; Z = 4. As a common feature within all three
      crystal structures of rubidium triflate, the triflate anions are arranged in
      double layers with the lipophilic CF3 groups facing each other. The rubidium ions
      are located between the SO3 groups. The general packing is similar to the packing
      in cesium triflate. Rubidium triflate can be classified as a solid electrolyte
      with a specific ionic conductivity of sigma = 9.89 x 10(-9) S/cm at T = 384 K and
      sigma = 3.84 x 10(-6) S/cm at T = 481 K.

PMID- 16602779
TI  - Structural diversity of the oxovanadium organodiphosphonate system: a platform
      for the design of void channels.
AB  - The hydrothermal reactions of a vanadium source, an appropriate diphosphonate
      ligand, and water in the presence of HF provide a series of compounds with
      neutral V-P-O networks as the recurring structural motif. When the
      {O3P(CH2)(n)PO3}4- diphosphonate tether length n is 2-5, metal-oxide hybrids of
      type 1, [V2O2(H2O){O3P(CH2)(n)PO3}] x xH2O, are isolated. The type 1 oxides
      exhibit the prototypical three-dimensional (3-D) "pillared" layer architecture.
      When n is increased to 6-8, the two-dimensional (2-D) "pillared" slab structure
      of the type 2 oxides [V2O2(H2O)4{O3P(CH2)6PO3}] is encountered. Further
      lengthening of the spacer to n = 9 provides another 3-D structure, type 3,
      constructed from the condensation of pillared slabs to give V-P-O double layers
      as the network substructure. When organic cations are introduced to provide
      charge balance for anionic V-P-O networks, oxides of types 4-7 are observed. For
      spacer length n = 3, a range of organodiammonium cations are accommodated by the
      same 3-D "pillared" layer oxovanadium diphosphonate framework in the type 4
      materials [H3N(CH2)(n)NH3][V4O4(OH)2 {O3P(CH)3PO3}2] x xH2O [n = 2, x = 6 (4a); n
      = 3, x = 3 (4b); n = 4, x = 2 (4c); n = 5, x = 1 (4d); n = 6, x = 0.5 (4e); n =
      7, x = 0 (4f)] and [H3NR]y[V4O4(OH)2 {O3P(CH)3PO3}2] x xH2O [R = -CH2(NH3)CH2CH3,
      y = 1, x = 0 (4g); R = -CH3, n = 2, x = 3 (4h); R = -CH2CH3, y = 2, x = 1 (4i); R
      = -CH2CH2CH3, y = 2, x = 0 (4j); cation = [H2N(CH2CH3)2], y = 2, x = 0 (4k)].
      These oxides exhibit two distinct interlamellar domains, one occupied by the
      cations and the second by water of crystallization. Furthermore, as the length of
      the cation increases, the organodiammonium component spills over into the
      hydrophilic domain to displace the water of crystallization. When the
      diphosphonate tether length is increased to n = 5, structure type 5,
      [H3N(CH2)2NH3][V4O4(OH)2(H2O){O3P(CH2)5PO3}2] x H2O, is obtained. This oxide
      possesses a 2-D "pillared" network or slab structure, similar in gross profile to
      that of type 2 oxides and with the cations occupying the interlamellar domain. In
      contrast, shortening the diphosphonate tether length to n = 2 results in the 3-D
      oxovanadium organophosphonate structure of the type 7 oxide
      [H3N(CH2)5NH3][V3O3{O3P(CH2)2PO3}2]. The ethylenediphosphonate ligand does not
      pillar V-P-O networks in this instance but rather chelates to a vanadium center
      in the construction of complex polyhedral connectivity of 7. Substitution of
      piperazinium cations for the simple alkyl chains of types 4, 5, and 7 provides
      the 2-D pillared layer structure of the type 6 oxides,
      [H2N(CH2CH2)NH2][V2O2{O3P(CH)(n)PO3H}2] [n = 2 (6a); n = 4 (6b); n = 6 (6c)]. The
      structural diversity of the system is reflected in the magnetic properties and
      thermal behavior of the oxides, which are also discussed.

PMID- 16602780
TI  - Parametrization of the magnetic behavior of the triangular spin ladder chains
      organically templated: (C2N2H10)[M(HPO3)F3] (M(III) = Fe, Cr, and V). Crystal
      structure and thermal and spectroscopic properties of the iron(III) phase.
AB  - A new iron(III) phosphite templated by ethylenediamine has been synthesized using
      solvothermal conditions under autogenous pressure. The (C2N2H10)[Fe(HPO3)F3]
      compound has been characterized by single-crystal X-ray diffraction data and
      spectroscopic and magnetic techniques. The crystal structure is formed by chains
      extended along the c axis and surrounded by ethylenediammonium cations. A study
      by diffuse-reflectance spectroscopy has been performed, and the calculated Dq, B,
      and C parameters for the Fe(III) cations are 1030, 720, and 3080 cm(-1),
      respectively. The Mossbauer spectrum at room temperature is characteristic of
      Fe(III) ions. The electron spin resonance (ESR) spectra carried out at different
      temperatures show isotropic signals with a g value of 2.00(1). The thermal
      evolution of the intensity of the ESR signals indicates the existence of
      antiferromagnetic interactions for the Fe(III) phase. The magnetic susceptibility
      data of the Cr(III) and V(III) compounds show antiferromagnetic couplings. The J
      exchange parameters of the Fe(III) and Cr(III) compounds have been calculated by
      using a model for a triangular spin ladder chain. The values are J1 = -1.63(1) K
      and J2 = -0.87(2) K with g = 2.02 for the Fe(III) phase and J(1) = -0.56(2) K and
      J2 = -0.40(2) K with g = 1.99 for the Cr(III) compound. In the case of the V(III)
      phase, the fit has been performed considering a linear chain with the magnetic
      parameters D = 2.5 cm(-1) and J = -1.15(1) K.

PMID- 16602781
TI  - Homoleptic alkaline earth metal bis(trifluoromethanesulfonyl)imide complex
      compounds obtained from an ionic liquid.
AB  - The first homoleptic alkaline earth bis(trifluoromethanesulfonyl)imide (Tf2N)
      complexes [mppyr]2[Ca(Tf2N)4], [mppyr]2[Sr(Tf2N)4], and [mppyr][Ba(Tf2N)3] were
      crystallized from a solution of the respective alkaline earth
      bis(trifluoromethanesulfonyl)imide and the ionic liquid [mppyr][Tf2N] (mppyr =
      1,1-N-methyl-N-propylpyrrolidinium). In the calcium and strontium compounds, the
      alkaline earth metal (AE) is coordinated by four bidentately chelating Tf2N
      ligands to form isolated (distorted) square antiprismatic [AE(Tf2N)4]2- complexes
      which are separated by N-methyl-N-propylpyrrolidinium cations. In contrast, the
      barium compound, [mppyr][Ba(Tf2N)3], forms an extended structure. Here the
      alkaline earth cation is surrounded by six oxygen atoms belonging to three Tf2N-
      anions which coordinate in a bidentate chelating fashion. Three further oxygen
      atoms of the same ligands are linking the Ba2+ cations to infinite
      (infinity)(1)[Ba(Tf2N)3] chains.

PMID- 16602782
TI  - Hexagonal and prismatic nanowalled ZnO microboxes.
AB  - We hereby report hydrothermal syntheses of new microstructures of semiconducting
      ZnO. Single-crystalline prismatic ZnO microboxes formed by nanowalls and
      hexagonal hollow microdisks closed by plates with micron-sized inorganic
      fullerene-like structures have been made in a base-free medium through a one-step
      hydrothermal synthesis with the help of n-butanol (NB). Structures and
      morphologies of the products were confirmed by results from powder X-ray
      diffraction and scanning electron microscopy. NB has been found to play a crucial
      role in the growth of these hollow structures. It is indicated that these hollow
      ZnO crystals were grown from redissolution of interiors. These ZnO microboxes
      exhibit a band emission in the visible range, implying the possession of a high
      content of defects.

PMID- 16602783
TI  - Underlying spin-orbit coupling structure of intervalence charge transfer bands in
      dinuclear polypyridyl complexes of ruthenium and osmium.
AB  - The mixed-valence systems meso- and rac-[{M(bpy)2}2(mu-BL)]5+ {M = Ru, Os; BL = a
      series of polypyridyl bridging ligands such as 2,3-bis(2-pyridyl)benzoquinoxaline
      (dpb)} are characterized by multiple intervalence charge transfer (IVCT) and
      interconfigurational (IC) bands in the mid-infrared and near-infrared (NIR)
      regions. Differences in the relative energies of the IC transitions for the fully
      oxidized (+6) states of the osmium systems demonstrate that stereochemical
      effects lead to fundamental changes in the energy levels of the metal-based dpi
      orbitals, which are split by spin-orbit coupling and ligand-field asymmetry. An
      increase in the separation between the IC bands as BL is varied reflects the
      increase in the degree of electronic coupling through the series of ruthenium and
      osmium complexes. The increase in the IVCT bandwidths for the former is therefore
      attributed to the increase in the separation of the three underlying components
      of the bands. Stark effect measurements reveal small dipole moment changes
      accompanying IVCT excitation in support of the localized-to-delocalized or
      delocalized classification for the dinuclear ruthenium and osmium systems.

PMID- 16602784
TI  - Hybrid organic-inorganic conductor with a magnetic chain anion: kappa
      BETS2[Fe(III)(C2O4)Cl2] [BETS = bis(ethylenedithio)tetraselenafulvalene].
AB  - The synthesis, crystal structure, and electrical, optical, and magnetic
      properties of kappa-BETS2[Fe(III)(C2O4)Cl2], where BETS is
      bis(ethylenedithio)tetraselenafulvalene, are reported. The black plate crystals
      consist of parallel donor layers, two per unit cell, displaying a kappa-type
      packing of BETS(0.5+) within the bc plane and anionic magnetic chains,
      [Fe(C2O4)Cl2-]n, running along the c axis. It displays metallic behavior down to
      4.2 K, and analysis of the optical reflectivity data gives unscreened plasma
      energies of 0.69 eV (E parallel c) and 0.40 eV (E perpendicular c). The optical
      anisotropy is larger than that seen for other kappa phases and is described well
      by transfer integrals obtained from extended Huckel calculations. However, the
      transfer integrals need to be scaled down uniformly by a factor of 1.21 to
      reproduce the absolute experimental plasma frequencies. The band structure
      consists of a one-dimensional (1D) band and a hole pocket, characteristics of
      kappa phases. The magnetic properties were modeled by the sum of a 1D
      antiferromagnetic chain contribution from the d spins of Fe3+, a temperature
      independent paramagnetic contribution, and a Curie impurity term. At 4.5 K, there
      is a signature of long-range magnetic ordering to a canted-antiferromagnetic
      state in the zero-field-cooled-field-cooled magnetizations, and at 2 K, a small
      hysteresis loop is observed.

PMID- 16602785
TI  - Syntheses and structures of two low-dimensional beryllium phosphate compounds:
      [C5H14N2]2[Be3(HPO4)5].H2O and [C6H18N2]0.5[Be2(PO4)(HPO4)OH].0.5H2O.
AB  - The first two low-dimensional beryllium phosphates, [C5H14N2]2[Be3(HPO4)5].H2O
      (BePO-CJ29) and [C6H18N2]0.5[Be2(PO4)(HPO4)OH].0.5 H2O (BePO-CJ30), have been
      successfully synthesized under mild hydrothermal/solvothermal conditions. BePO
      CJ29 is built up from strict alternation of BeO4 and HPO4 tetrahedra forming a
      unique one-dimensional double chains with 12-ring apertures. There are pseudo-10
      ring apertures enclosed by two double chains through H-bonds. BePO-CJ29 can also
      be viewed as a pseudo 2-D layered structure stabilized by strong H-bonds. The
      diprotonated 2-methylpiperazium cations are located at three positions (i.e.,
      inside the 12-ring aperture, inside the pseudo-10-ring aperture, and in the
      interlayer of the inorganic pseudo-layers. BePO-CJ30 is constructed by the
      alternation of Be-centered tetrahedra (including BeO4 and HBeO4) and P-centered
      tetrahedra (including PO4 and HPO4) resulting in a two-dimensional layered
      structure parallel to the (0 1 1) direction. The complex layer is composed of
      coupled 4.8 net sheets. The diprotonated 1,6-hexandiamine cations and water
      molecules reside in the interlayer regions and interact with the inorganic layers
      through H-bonds. Crystal data are as follows: [C5H14N2]2[Be3(HPO4)5].H2O (BePO
      CJ29), triclinic, P1 (No. 2), a = 8.1000(9) A, b = 8.4841(14) A, c = 19.665(2) A,
      alpha = 89.683(10) degrees, beta = 78.182(8) degrees, gamma = 87.932(9) degrees,
      V = 1321.9(3) A3, Z = 2, R1 = 0.0523 (I > 2sigma(I)), and wR2 = 0.1643 (all
      data); [C6H18N2]0.5[Be2(PO4)(HPO4)OH].0.5 H2O (BePO-CJ30), orthorhombic, Pccn
      (No. 56), a = 26.01(4) A, b = 8.431(12) A, c = 9.598(13) A, V = 2105(5) A3, Z =
      8, R1 = 0.0833 (I > 2sigma(I)), and wR2 = 0.2278 (all data).

PMID- 16602786
TI  - Novel 3D, 2D, and 0D first-row coordination compounds with 4,4'-bipyridine-N,N'
      dioxide incorporating sulfur-containing anions.
AB  - The reaction of M(S2O6) (M = Cu(II), Ni(II), and Co(II)) with 4,4'-bipyridine
      N,N'-dioxide (bpdo) results in the formation of novel 3D, 2D, and mononuclear
      complexes. Complex 1, {[Cu(H2O)(bpdo)2](S2O6)(H2O)}n, is a 2-D wavelike polymer
      with the Cu(II) ion located on a 2-fold axis and having a distorted square
      pyramidal coordination sphere. With Co(II) and Ni(II), 3-D complexes,
      {[M(bpdo)3](S2O6)(C2H5OH)7}n [M = Co(II) (2), Ni(II) (3)], were obtained. The
      metal atoms are situated on centers of symmetry and have octahedral environments
      coordinated to six bpdo molecules. The same reaction in aqueous solution with a
      metal/ligand ratio of 1:1 results in the formation of mononuclear complexes,
      {[M(bpdo)(H2O)5](SO4)(H2O)2} [M = Co(II) (4), Ni(II) (5)], accompanied by the
      decomposition of the dithionate anions S2O6(2-) to sulfate anions SO4(2-).

PMID- 16602787
TI  - The mixed-valent manganese [3 x 3] grid [Mn(III)4Mn(II)5(2poap-2H)6](ClO4)10.10
      H2O, a mesoscopic spin-1/2 cluster.
AB  - The magnetic susceptibility and low-temperature magnetization curve of the [3 x
      3] grid [Mn(III)4Mn(II)5(2poap-2H)6](ClO4)10.10 H2O (1) are analyzed within a
      spin Hamiltonian approach. The Hilbert space is huge (4,860,000 states), but the
      consequent use of all symmetries and a two-step fitting procedure nevertheless
      allows the best-fit determination of the magnetic exchange parameters in this
      system from complete quantum mechanical calculations. The cluster exhibits a
      total spin S = 1/2 ground state; the implications are discussed.

PMID- 16602788
TI  - Weak metamagnetic-like 1D manganese(II) complex with a double mu(1,1)-azido
      bridge: a structure and magnetic study.
AB  - The azido-bridged manganese complex of formula [Mn(tptz)(mu(1,1)-N3)2]n [1; tptz
      = 2,4,6-tris(2-pyridyl)-1,3,5-triazine] has been synthesized and characterized by
      single-crystal X-ray diffraction analysis and a low-temperature magnetic study.
      The complex 1 crystallizes in the orthorhombic space group Pbcn, with a =
      17.911(5) A, b = 15.804(5) A, c = 6.6538(18) A, and Z = 4. The Mn atoms are
      coordinated by three N atoms of the tptz ligands and connected to each other by
      double end-on (EO) azide ligands, forming a neutral 1D chain. The adjacent 1D
      chains are connected by face-to-face pi-pi-stacking interactions and C-H...pi
      interactions of pyridine rings of the tptz ligands, which leads to the formation
      of a supramolecular 2D sheet structure. Temperature- and field-dependent magnetic
      analyses reveal dominant intrachain ferromagnetic interactions with EO azide
      bridge and weak interchain antiferromagnetic interactions with overall
      metamagnetic behavior having 3D magnetic ordering at 2.7 K. The critical field is
      approximately 80 G, at which the interlayer antiferromagnetic ground-state
      switches to a ferromagnetic state.

PMID- 16602789
TI  - Structures and bonding in K0.91U1.79S6 and KU2Se6.
AB  - The compounds K0.91U1.79S6 and KU2Se6, members of the AAn2Q6 actinide family (A =
      alkali metal or Tl; An = Th or U; Q = S, Se, or Te), have been synthesized from
      US2, K2S, and S at 1273 K and U, K2Se, and Se at 1173 K, respectively. KU2Se6
      shows Curie-Weiss behavior above 30 K and no magnetic ordering down to 5 K. The
      value of mu(eff) is 2.95(1) mu(B)/U. Its electronic spectrum shows the peaks
      characteristic of 5f-5f transitions. It is a semiconductor with an activation
      energy of 0.27 eV for electrical conduction. Both K0.91U1.79S6 and KU2Se6
      crystallize in space group Immm of the orthorhombic system and are of the KTh2Se6
      structure type. Both contain infinite one-dimensional linear Q-Q chains
      characteristic of the AAn2Q6 family. Typical of the known AAn2Q6 compounds, in
      KU2Se6, there are two alternating Se-Se distances of 2.703(2) and 2.855(2) A,
      both much longer than an Se-Se single bond. In contrast, in K0.91U1.79S6, the
      first sulfide of this family to be characterized structurally, there are
      alternating normal S2(2-) pairs 2.097(5) A in length. In K0.91U1.79S6, the formal
      oxidation state of U is 4+.

PMID- 16602790
TI  - Synthesis and characterization of aluminum-containing tin(IV) heterobimetallic
      sulfides.
AB  - Three novel aluminum-containing tin(IV) heterobimetallic sulfides are reported.
      The reaction of [LAl(SLi)2(THF)2]2 (1) [L = HC(CMeNAr)2, Ar = 2,6-iPr2C6H3] with
      Ph2SnCl2, Me2SnCl2, and SnCl4 in THF respectively afforded LAl(mu-S)2SnPh2 (2),
      LAl(mu-S)2SnMe2 (3), and LAl(mu-S)2Sn(mu-S)2AlL (4) in moderate yields. Compounds
      2, 3, and 4 were characterized by elemental analysis, NMR, electron-impact mass
      spectrometry, and single-crystal X-ray structural analysis.

PMID- 16602791
TI  - Toward an accurate determination of 195Pt chemical shifts by density functional
      computations: the importance of unspecific solvent effects and the dependence of
      Pt magnetic shielding constants on structural parameters.
AB  - Density functional theory using the zero-order regular approximate two-component
      relativistic Hamiltonian has been applied to calculate the 195Pt chemical shifts
      for the complexes [PtCl6]2-, [PtCl4]2-, and
      [Pt2(NH3)2Cl2((CH3)3CCONH)2(CH2COCH3)]Cl. It is demonstrated that, in contrast to
      recent findings by other authors, platinum chemical shift calculations require
      not only a basis set beyond polarized triple-zeta quality for the metal atom but
      also, in principle, the consideration of explicit solvent molecules in addition
      to a continuum model for the first two complexes. We find that the inclusion of
      direct solvent-solute interactions at the quantum mechanical level is important
      for obtaining reasonable results despite that fact that these solvent effects are
      rather nonspecific. The importance of solvent effects has also implications on
      how experimental data should be interpreted. Further, in contrast to several
      previous studies of heavy-metal NMR parameters, functionals beyond the local
      density approximation were required both in the geometry optimization and the NMR
      calculations to obtain reasonable agreement between the computed and experimental
      NMR data. This comes with the disadvantage, however, of increased Pt-ligand bond
      distances leading to less good agreement with experiment for structural data. A
      detailed analysis of the results for the two chloroplatinate complexes is
      presented. The same computational procedure has then been applied to the
      dinuclear Pt(III) complex. Chemical shifts have been calculated with respect to
      both [PtCl6]2- and [PtCl4]2- chosen as the NMR reference, yielding good agreement
      with experiment. The determination of preferred solvent locations around the
      complexes studied turned out to be important for reproducing experimental data.

PMID- 16602792
TI  - Silver(I) coordination polymers based on a nano-sized bent bis(3-acetylenylphenyl
      (4-cyanophenyl))oxadiazole ligand: the role of ligand isomerism and the
      templating effect of polyatomic anions and solvent intermediates.
AB  - One nanosized oxadiazole bridging ligand, bis(3-acetylenylphenyl-(4
      cyanophenyl))oxadiazole (L11), was designed and synthesized by the reaction of
      bis(3-iodophenyl)oxadiazole with 4-cyanophenylacetylene via a Sonogashira
      Hagihara cross-coupling reaction. Eight Ag(I)-L11 coordination polymers with one
      , two-, or three-dimensional structures have been successfully prepared by the
      reaction of L11 with various Ag(I) salts in solution. New coordination polymers
      were fully characterized by infrared spectroscopy, elemental analysis, and single
      crystal X-ray diffraction. All new complexes contain silver heteroatom cluster
      connecting nodes, and the L11 ligand is "doubling up" in the frameworks. In this
      Ag(I)-L11 system, the conformation of L11 is versatile because of the
      conformational rotation around the central oxadiazole moiety and depends greatly
      on the counterion and solvent system used in the formation of the complexes. In
      addition, the luminescence property and host-guest chemistry of some complexes
      were investigated primarily.

PMID- 16602793
TI  - Assembly of lipophilic tetranuclear (Cu4 and Zn4) molecular metallophosphonates
      from 2,4,6-triisopropylphenylphosponic acid and pyrazole ligands.
AB  - A sterically hindered aryl phosphonic acid ArP(O)(OH)2 (2) (Ar = 2,4,6
      isopropylphenyl) was synthesized and structurally characterized. ArP(O)(OH)2
      forms an interesting hydrogen-bonded corrugated sheet-type supramolecular
      structure in the solid-state. A three-component reaction involving ArP(O)(OH)2,
      3,5-dimethylpyrazole(DMPZH), and Cu(CH3COO)2.H2O produces the tetranuclear Cu(II)
      compound [Cu4(mu3-OH)2{ArPO2(OH)}2(CH3CO2)2(DMPZH)4][CH3COO]2.CH2Cl2 (3). A
      similar three-component reaction involving ArP(O)(OH)2, 3,5-dimethylpyrazole, and
      Zn(CH3COO)2.2H2O yields the tetranuclear Zn(II) compound
      [Zn4{ArPO3}2{ArPO2(OH)}2{DMPZH}4(DMPZ)2].5MeOH (4). While 3 has been found to
      have an asymmetric cage structure where two dinuclear copper cores are bridged by
      bidentate [ArPO2(OH)]- ligands, 4 possesses an open-book tricyclic structure
      composed of three fused metallophosphonate rings. Magnetic studies on 3 revealed
      antiferromagnetic behavior.

PMID- 16602794
TI  - Imino sulfinamidines: synthesis and coordination chemistry of a novel class of
      chiral bidentate ligands.
AB  - The new imino sulfinamidine ligand PhS(NHt-Bu)=NC(Me)=N(C6H3-2,6-iPr2), LH (11)
      was synthesized from N-(2,6-diisopropylphenyl)acetamidine (9) and N-tert-butyl
      phenylsulfinimidoyl chloride (10). Reaction of LH (11) with ZnEt2 or AlMe3 gave
      the complexes LZnEt (12) and LAlMe2 (13), respectively. The structures of 12 and
      13 were determined by X-ray diffraction and were shown to contain L as a kappa2
      N1,N5 bidentate ligand in a six-membered chelate. Formation of the magnesium
      complex (LMgN(TMS)2 x L2Mg) (14) from 11, MgI2, and KN(SiMe3)2 highlighted a
      secondary coordination mode of L, binding through the sulfinamidine nitrogens in
      a four-membered chelate.

PMID- 16602795
TI  - Metal coordination by sterically hindered heterocyclic ligands, including 2
      vinylpyridine, assessed by investigation of cobaloximes.
AB  - Structural and 1H NMR data have been obtained for cobaloximes with the bulkiest
      substituted pyridines reported so far. We have isolated in noncoordinating
      solvents the complexes CH3Co(DH)2L (methylcobaloxime, where DH = the monoanion of
      dimethylglyoxime) with L = sterically hindered N-donor ligands: quinoline, 4
      CH3quinoline, 2,4-(CH3)2pyridine, and 2-R-pyridine (R = CH3, OCH3, CH2CH3,
      CH=CH2). We have found that the Co-N(ax) bond is very long in the structurally
      characterized complexes. In particular, CH3Co(DH)2(4-CH3quinoline) has a longer
      Co-N(ax) bond (2.193(3) A) than any reported for methylcobaloximes. The main
      cause of the long bonds is unambiguously identified as the steric bulk of L by
      the fairly linear relationship found for Co-N(ax) distance vs CCA (calculated
      cone angle, CCA, a computed measure of bulk) over an extensive series of
      methylcobaloximes. The linear relationship improves if L basicity (quantified by
      pKa) is taken into account. In anhydrous CDCl3 at 25 degrees C, all complexes
      except the 2-aminopyridine adduct exhibit 1H NMR spectra consistent with partial
      dissociation of L to form the methylcobaloxime dimer. 1H NMR experiments at -20
      degrees C allowed us to assess qualitatively the relative binding ability of L as
      follows: 2,4-(CH3)2pyridine > 4-CH3quinoline approximately = quinoline
      approximately = 2-CH3pyridine > 2-CH3Opyridine > 2-CH3CH2pyridine > 2
      CH2=CHpyridine. The broadness of the 1H NMR signals at 25 degrees C suggests a
      similar order for the ligand exchange rate. The lack of dissociation by 2
      aminopyridine is attributed to an intramolecular hydrogen bond between the NH2
      group and an oxime O atom. The weaker than expected binding of 2-vinylpyridine
      relative to the Co-N(ax) bond length is attributed to rotation of the 2-vinyl
      group required for this bulky ligand to bind to the metal center, a conclusion
      supported by pronounced changes in 2-vinylpyridine signals upon coordination.

PMID- 16602796
TI  - Syntheses and molecular structure of some Rh and Ru complexes with the chelating
      diphenyl (2-pyridyl)phosphine ligand.
AB  - The rhodium(III) complex mer,cis-[RhCl3(PPh2py-P,N)(PPh2py-P)] (1) (PPh2py =
      diphenyl (2-pyridyl)phosphine) has been prepared from RhCl3 x 3H2O and PPh2py and
      converted to the trans,cis-[RhCl2(PPh2py-P,N)2]PF6 (2) in acetone solution by
      treatment with Ag+ and PF6(-). Ruthenium(III) and ruthenium(II) compounds with
      PPh2py, mer,cis-[RuCl3(PPh2py-P,N)(PPh2py-P)] (3) and mer-[RuCl(PPh2py
      P,N)2(PPh2py-P)]Cl (5) have been obtained from DMSO precursor complexes. In a
      chloroform solution, complex (5) isomerizes to fac-[RuCl(PPh2py-P,N)2(PPh2py
      P)]Cl (fac-5). All compounds have been characterized by MS, UV-vis, IR, and 1H
      and 31P{1H} NMR spectroscopy, and the Ru(III) compound has been characterized by
      EPR spectroscopy as well. The crystal structures of 1, 2, 3, and fac-5 have been
      determined. In all compounds under investigation, at least one pyridylphosphine
      acts as a chelate ligand. The 31P chemical shifts for chelating PPh2py-P,N depend
      on the Ru-P bond lengths.

PMID- 16602797
TI  - Investigation of tetrahedral mixed-metal carbonyl clusters by two-dimensional
      59Co COSY and DQFCOSY NMR experiments.
AB  - Two-dimensional (2D) 59Co correlation spectroscopy (COSY)/double-quantum-filtered
      (DQF)COSY experiments are reported for three tetrahedral mixed-metal clusters
      HFeCo3(CO)11L with L = PPh3, P(OMe)3, and PCy3 (Cy = cyclohexyl) in which the L
      substituted Co center is chemically different from the other two. The 2D 59Co
      COSY and DQFCOSY NMR spectra of these clusters in solution prove the existence of
      a scalar coupling constant between the 59Co nuclei. To determine this value for
      each cluster, 2D 59Co COSY and DQFCOSY NMR spectra have been simulated by
      numerical density-matrix calculations. The predicted spectra mimic well the
      features of the experimental spectra if a scalar coupling is introduced between
      the Co nuclei. It was initially observed that the scalar coupling constants
      between the Co nuclei obtained from the 2D COSY and DQFCOSY NMR spectra differed
      significantly. In contrast to the 2D COSY spectra, the diagonal and cross peaks
      are of comparable intensity in the 2D DQFCOSY spectra, which leads to a
      considerable increase in the accuracy of the determination of the scalar coupling
      constant.

PMID- 16602798
TI  - Unsaturation in binuclear cyclopentadienyliron carbonyls.
AB  - The binuclear cyclopentadienyliron carbonyls Cp2Fe2(CO)n (n = 4, 3, 2, 1; Cp =
      eta(5)-C5H5) have been studied by density functional theory (DFT) using the B3LYP
      and BP86 methods. The trans- and cis-Cp2Fe2(CO)2(mu-CO)2 isomers of Cp2Fe2(CO)4
      known experimentally are predicted by DFT methods to be genuine minima with no
      significant imaginary vibrational frequencies. The energies of these two
      Cp2Fe2(CO)2(mu-CO)2 structures are very similar, consistent with the experimental
      observation of an equilibrium between these isomers in solution. An intermediate
      between the interconversion of the trans- and cis-Cp2Fe2(CO)2(mu-CO)2 dibridged
      isomers of Cp2Fe2(CO)4 can be the trans unbridged isomer of Cp2Fe2(CO)4
      calculated to be 2.3 kcal/mol (B3LYP) or 9.1 kcal/mol (BP86) above the global
      minimum trans-Cp2Fe2(CO)2(mu-CO)2. For the unsaturated Cp2Fe2(CO)3, the known
      triplet isomer Cp2Fe2(mu-CO)3 with an Fe=Fe double bond similar to the O=O double
      bond in O2 is found to be the global minimum. The lowest-energy structure for the
      even more unsaturated Cp2Fe2(CO)2 is a dibridged structure Cp2Fe2(mu-CO)2, with a
      short Fe-Fe distance suggestive of the Fe[triple bond]Fe triple bond required to
      give both Fe atoms the favored 18-electron configuration. Singlet and triplet
      unbridged structures for Cp2Fe2(CO)2 were also found but at energies considerably
      higher (20-50 kcal/mol) than that of the global minimum Cp2Fe2(mu-CO)2. The
      lowest-energy structure for Cp2Fe2(CO) is the triplet unsymmetrically bridged
      structure Cp2Fe2(mu-CO), with a short Fe-Fe distance (approximately 2.1 A)
      suggestive of the sigma + 2pi + (2/2)delta Fe[quadruple bond]Fe quadruple bond
      required to give both Fe atoms the favored 18-electron rare gas configuration.

PMID- 16602799
TI  - EXAFS and IR structural study of platinum-based anticancer drugs' degradation by
      diethyl dithiocarbamate.
AB  - Platinum compounds constitute a discrete class of DNA-damaging anticancer drug
      agents, including cisplatin, carboplatin, and oxaliplatin. The toxicity of such
      drugs raises the problem of waste detoxification. Diethyl dithiocarbamate (DDTC)
      is recommended by the World Heath Organization (WHO) for the destruction of
      cisplatin, but the degradation product has not been structurally characterized.
      This paper deals with the extended X-ray absorption fine structure (EXAFS) and IR
      structural study of the reaction products of DDTC with cisplatin, carboplatin,
      and oxaliplatin. Cisplatin and carboplatin give the same reaction product:
      Pt(DDTC)2. In the case of oxaliplatin, we observed the formation of
      [(diaminocyclohexane)(DDTC)Pt(II)]. In all cases, the replacement of labile
      ligands by strong ligands should lead to inactive compounds. Our results suggest
      that the WHO inactivation protocol might be extended to carboplatin and
      oxaliplatin. Nevertheless, this should be validated by toxicity tests of the
      degradation products.

PMID- 16602800
TI  - The electronic ground state of [V(urea)6]3+ probed by NIR luminescence,
      electronic Raman, and high-field EPR spectroscopies.
AB  - The electronic structure of a trigonally distorted vanadium(III) complex,
      [V(urea)6](ClO4)3, and its deuterated analogue, [V(urea-d4)6](ClO4)3 has been
      investigated with Raman, luminescence, and high-frequency high-field electron
      paramagnetic resonance spectroscopies and with magnetic measurements. A broad
      electronic Raman transition is observed at around 1400 cm(-1) and attributed to a
      transition to the (3)E (D3) component of the (3)T1g (O(h)) ground state. The same
      splitting is seen in the near-infrared luminescence spectrum in the form of a
      similarly broad peak at 8450 cm(-1), 1400 cm(-1) lower in energy than the (1)E -
      > (3)A2 spin-flip transition. Powder high-frequency and high-field electron
      paramagnetic resonance spectra, magnetic susceptibilities, and magnetization
      studies give a precise measurement of the zero-field splitting and of the g
      values in this complex (D = 6.00(2) cm(-1), E = 0.573(6) cm(-1), g(x) = 1.848(2),
      g(y) = 1.832(4), and g(z) = 1.946(7)). A set of angular overlap model parameters
      is proposed that reproduces all spectroscopic observations, and an analysis of
      the influence of the bonding of urea on the trigonal distortion of the complex is
      given.

PMID- 16602801
TI  - Crystallization of zeolites from organo-silicic colloids.
AB  - As shown recently, the networks of mesoporous high-surface-area silicates and
      zeolites undergo a deep depolymerization process in glycerol, near 200 degrees C.
      Within 1 h, X-ray diffraction analysis amorphous gels are obtained. However, some
      local ordering subsists as demonstrated by a striking similarity between the
      silicon and aluminum high-resolution solid-state NMR spectra before and after the
      reaction. The residual organization could be investigated indirectly in studying
      the recrystallization of these gels in the presence or absence of structure
      directing agents. Were this attempt successful, the way should be opened for the
      synthesis of molecular sieves starting from gels obtained from naturally
      occurring zeolites. Here, it will be shown that an amorphous gel obtained from
      HZSM-5 recovers the initial long-range structure of the parent material in a few
      hours at 85 degrees C in the presence of an aqueous solution of tetrapropyl
      ammonium (TPA) or NH3. The recrystallization of HY requires the presence of
      tetramethylammonium, but about 25% of the crystallization is obtained rapidly
      (approximately = 1 day) at 80 degrees C with ammonia. Hypotheses about the
      preorganized structural units are presented. The value of the Si-O-Si angle in
      the silica cluster seems to be of paramount importance.

PMID- 16602802
TI  - Oxidation of iodide by a series of Fe(III) complexes in acetonitrile.
AB  - The oxidations of iodide by [Fe(III)(bpy)2(CN)2]NO3, [Fe(III)(dmbpy)2(CN)2]NO3,
      [Fe(III)(CH3Cp)2]PF6, and [Fe(III)(5-Cl-phen)2(CN)2]NO3 at 25 degrees C, ionic
      strength of 0.10 M in acetonitrile, are catalyzed by trace levels of copper ions.
      This copper catalysis can be effectively masked with the addition of 5.0 mM 2,2'
      bipyridine (bpy), which permits the rate law of the direct reactions to be
      determined: -d[Fe(III)]/dt = 2(k1[I-] + k2[I-]2)[Fe(III)]. According to 1H NMR
      and UV-vis spectra, the products of the reaction are I3- and the corresponding
      Fe(II) complexes, with the stoichiometric ratio (delta[I3-]/delta[Fe(II)]) of
      1:2. Linear free-energy relationships (LFERs) are obtained for both log k1 and
      log k2 vs E(1/2) with slopes of 16.1 and 13.3 V(-1), respectively. A mechanism is
      inferred in which k1 corresponds to simple electron transfer to form I* plus
      Fe(II), while k2 leads directly to I2(-*). From the mild kinetic inhibition of
      the k1 path by [Fe(II)(bpy)2(CN)2] the standard potential (Eo) of I*/I- is
      derived: Eo = 0.60 +/- 0.01 V (vs [Fe(Cp)2](+/0)).

PMID- 16602804
TI  - Lanthanum and alkali metal coordination chemistry of the
      bis(dimethylphenylsilyl)amide ligand.
AB  - The coordination chemistry of the bis(dimethylphenylsilyl)amide ligand,
      [N(SiMe2Ph)2]1-, with sodium, potassium, and lanthanum has been investigated for
      comparison with the more commonly used [N(SiMe3)2]1- and [N(SiHMe2)2]1- ligands.
      HN(SiMe2Ph)2 reacts with KH to produce KN(SiMe2Ph)2, 1, which crystallizes from
      toluene as the dimer [KN(SiMe2Ph)2(C7H8)]2, 2. The structure of 2 shows that the
      [N(SiMe2Ph)2]1- ligand can function as a polyhapto ligand with coordination from
      each phenyl group as well as the normal nitrogen ligation and agostic methyl
      interactions common in methylsilylamides. Each potassium in 2 is ligated by an
      eta4-toluene, two bridging nitrogen atoms, and an eta2-phenyl, an eta1-phenyl,
      and an eta1-methyl group. KN(SiMe2Ph)2 crystallizes from toluene in the presence
      of 18-crown-6 to make the monometallic complex (18-crown-6)KN(SiMe2Ph)2, 3, in
      which [N(SiMe2Ph)2]1- functions as a simple monodentate ligand through nitrogen.
      The reaction of HN(SiMe2Ph)2 with NaH in THF at reflux for 2 days generates
      Na[N(SiMe2Ph)2], 4, which crystallizes as the solvated dimer {(THF)Na[mu
      eta1:eta1-N(SiMe2Ph)2]}2, 5. A lanthanide metallocene derivative of
      [N(SiMe2Ph)2]1- was obtained by reaction of K[N(SiMe2Ph)2] with [(C5Me5)2La][(mu
      Ph)2BPh2]. Crystals of (C5Me5)2La[N(SiMe2Ph)2], 6, show agostic interactions
      between lanthanum and methyl groups of each silyl substituent. The [N(SiMe3)2]1-
      analogue of 3, (18-crown-6)KN(SiMe3)2, 7, was also structurally characterized for
      comparison.

PMID- 16602803
TI  - Synthetic analogues of the active site of the A-cluster of acetyl coenzyme A
      synthase/CO dehydrogenase: syntheses, structures, and reactions with CO.
AB  - Two metallosynthons, namely (Et4N)2[Ni(NpPepS)] (1) and (Et4N)2[Ni(PhPepS)] (2)
      containing carboxamido-N and thiolato-S as donors have been used to model the
      bimetallic M(p)-Ni(d) subsite of the A-cluster of the enzyme acetyl coenzyme A
      synthase/CO dehydrogenase. A series of sulfur-bridged Ni/Cu dinuclear and
      trinuclear complexes (3-10) have been synthesized to explore their redox
      properties and affinity of the metal centers toward CO. The structures of
      (Et4N)2[Ni(PhPepS)] (2), (Et4N)[Cu(neo)Ni(NpPepS)] x 0.5 Et2O x 0.5 H2O (3 x 0.5
      Et2O x 0.5 H2O), (Et4N)[Cu(neo)Ni(PhPepS)] x H2O (4 x H2O),
      (Et4N)2[Ni{Ni(NpPepS)}2] x DMF (5 x DMF), (Et4N)2[Ni(DMF)2{Ni(NpPepS)}2] x 3 DMF
      (6 x 3 DMF), (Et4N)2[Ni(DMF)2{Ni(PhPepS)}2] (8), and [Ni(dppe)Ni(PhPepS)] x
      CH2Cl2 (10 x CH2Cl2) have been determined by crystallography. The Ni(d) mimics 1
      and 2 resist reduction and exhibit no affinity toward CO. In contrast, the sulfur
      bridged Ni center (designated Ni(C)) in the trinuclear models 5-8 are amenable to
      reduction and binds CO in the Ni(I) state. Also, the sulfur-bridged Ni(C) center
      can be removed from the trimers (5-8) by treatment with 1,10-phenanthroline much
      like the "labile Ni" from the enzyme. The dinuclear Ni-Ni models 9 and 10
      resemble the Ni(p)-Ni(d) subsite of the A-cluster more closely, and only the
      modeled Ni(p) site of the dimers can be reduced. The Ni(I)-Ni(II) species display
      EPR spectra typical of a Ni(I) center in distorted trigonal bipyramidal and
      distorted tetrahedral geometries for 9(red) and 10(red), respectively. Both
      species bind CO, and the CO-adducts 9(red)-CO and 10(red)-CO display strong
      nu(co) at 2044 and 1997 cm(-1), respectively. The reduction of 10 is reversible.
      The CO-affinity of 10 in the reduced state and the nu(co) value of 10(red)-CO
      closely resemble the CO-bound reduced A-cluster (nu(co) = 1996 cm(-1)).

PMID- 16602805
TI  - Density functional theory studies of actinide(III) motexafins (An-Motex2+, An =
      Ac, Cm, Lr). Structure, stability, and comparison with lanthanide(III)
      motexafins.
AB  - Newly developed relativistic energy-consistent 5f-in-core actinide
      pseudopotentials and corresponding (7s6p5d1f)/[5s4p3d1f] basis sets in the
      segmented contraction scheme, combined with density functional theory methods,
      have been used to study the molecular structure and chemical properties of
      selected actinide(III) motexafins (An-Motex2+, An = Ac, Cm, Lr). Structure and
      stability are discussed, and a comparison to the lanthanide(III) motexafins (Ln
      Motex2+, Ln = La, Gd, Lu) is made. The actinide element is found to reside above
      the mean N5 motexafin plane, and the larger the cation, the greater the observed
      out-of-plane displacement. It is concluded that the actinium(III), curium(III),
      and lawrencium(III) cations are tightly bound to the macrocyclic skeleton,
      yielding stable structures. However, the calculated metal-ligand gas-phase
      binding energy for An-Motex2+ is about 1-2 eV lower than that of Ln-Motex2+,
      implying a lower stability of An-Motex2+ compared to Ln-Motex2+. Results
      including solvent effects imply that Ac-Motex2+ is the most stable complex in
      aqueous solution and should be the best candidate for experimentalists to get
      stable actinide(III) motexafin complexes.

PMID- 16602806
TI  - Synthesis and characterization of rhenium-copper sulfide cluster complexes
      [(Ph3P)2N][Re3(CuX)(mu3-S)4Cl6(PMe2Ph)3] (X = Cl, Br, I).
AB  - The reaction of a trinuclear rhenium sulfide cluster compound Re3S7Cl7 with
      dimethylphenylphosphine and CuX2 (X = Cl or Br) or CuX (X = Cl, Br, or I) formed
      tetranuclear cluster complexes [(Ph3P)2N][Re3(CuX)(mu3-S)4Cl6(PMe2Ph)3] (X = Cl,
      Br, or I). Their solutions have the characteristic intense blue color with
      visible spectral bands near 600 nm. Single-crystal X-ray structures show that
      three mu-S atoms in the intermediate trinuclear rhenium complex coordinate to a
      copper atom, forming elongated tetrahedral structures in which Re-Cu bonding
      interaction is negligible (Re-Cu distances are 3.50 to approximately 3.54 A as
      compared with Re-Re distances ranging from 2.69 to 2.81 A).

PMID- 16602807
TI  - Cu(I) dinuclear complexes with tripodal ligands vs monodentate donors:
      triphenylphosphine, thiourea, and pyridine. A 1H NMR titration study.
AB  - Complexes [PPh3Cu(Tr(Mes,Me))] (1), [PPh3Cu(Tr(Me,o-Py))] (2), and
      [PPh3Cu(Br(Mes)pz(o-Py))] (3) (Tr(Mes,Me) = hydrotris[1,4-dihydro-3-methyl-4
      mesityl-5-thioxo-1,2,4-triazolyl]borate; Tr(Me,o-Py) = hydrotris[1,4-dihydro-4
      methyl-3-(2-pyridyl)-5-thioxo-1,2,4-triazolyl]borate; Br(Mes)pz(o-Py) =
      hydro[bis(thioxotriazolyl)-3-(2-pyridyl)pyrazolyl]borate; PPh3 =
      triphenylphosphine) were synthesized by the reaction of dinuclear complexes
      [Cu(Tr(Mes,Me))]2, [Cu(Tr(Me,o-Py))]2, [Cu(Br(Mes)pz(o-Py))]2, and PPh3. 1-3 were
      characterized by 1H, 13C, and 31P NMR spectroscopy and ESI-mass spectrometry.
      Crystal structure analyses were performed for 1 and 2. Both complexes crystallize
      in the triclinic P space group with the metal in a slightly distorted tetrahedral
      geometry (S3P coordination) bound by a kappa3-S3 ligand and a PPh3 molecule. The
      solution molecular structures were investigated by means of variable-temperature
      (210-310 K, CDCl3, 1-2; 200-310 K, CD2Cl2, 3) and NOESY NMR spectroscopy. The
      solution structures of 1-2 are in accordance with the X-ray structures, and the
      complexes do not exhibit fluxional behavior. On the other hand, 3 is subject to
      an equilibrium between two species with a coalescing temperature of approximately
      260 K. DFT geometry optimizations suggest that the major species of 3 consists of
      the Br(Mes)pz(o-Py) ligand bound to Cu(I) in the kappa3-S2H fashion with two C=S
      groups and a [Cu...H-B] interaction. A PPh3 completes the copper coordination
      (S2HP coordination). The complex [TuCu(Tr(Mes,Me))] (4) (Tu = thiourea) was
      crystallized using an excess of Tu with respect to [Cu(Tr(Me,2-Py))]2
      (approximately a 6:1 ratio). The metal adopts a distorted tetrahedral geometry
      with an overall S3H coordination determined by the bound kappa3-S2H ligand (two
      C=S groups and a [B-H...Cu] interaction) and by a Tu. The reactivity of dinuclear
      complexes [Cu(Tr(Mes,Me))]2, [Cu(Tr(Me,o-Py))]2, and [Cu(Br(Mes)pz(o-Py))]2 with
      monodentate ligands was investigated by means of NMR titrations with PPh3, Tu.
      and pyridine (Py), and formation constants for the adducts [DCu(L)] (D =
      monodentate donor, L = tripodal ligand) were determined.

PMID- 16602808
TI  - Olefin epoxidation by the hydrogen peroxide adduct of a novel non-heme
      mangangese(IV) complex: demonstration of oxygen transfer by multiple mechanisms.
AB  - Olefin epoxidations are a class of reactions appropriate for the investigation of
      oxygenation processes in general. Here, we report the catalytic epoxidation of
      various olefins with a novel, cross-bridged cyclam manganese complex,
      Mn(Me2EBC)Cl2 (Me2EBC is 4,11-dimethyl-1,4,8,11
      tetraazabicyclo[6.6.2]hexadecane), using hydrogen peroxide as the terminal
      oxidant, in acetone/water (ratio 4:1) as the solvent medium. Catalytic
      epoxidation studies with this system have disclosed reactions that proceed by a
      nonradical pathway other than the expected oxygen-rebound mechanism that is
      characteristic of high-valent, late-transition-metal catalysts. Direct treatment
      of olefins with freshly synthesized [Mn(IV)(Me2EBC)(OH)2](PF6)2 (pKa = 6.86) in
      either neutral or basic solution confirms earlier observations that neither the
      oxo-Mn(IV) nor oxo-Mn(V) species is responsible for olefin epoxidization in this
      case. Catalytic epoxidation experiments using the 18O labels in an acetone/water
      (H2(18)O) solvent demonstrate that no 18O from water (H2(18)O) is incorporated
      into epoxide products even though oxygen exchange was observed between the Mn(IV)
      species and H2(18)O, which leads to the conclusion that oxygen transfer does not
      proceed by the well-known oxygen-rebound mechanism. Experiments using labeled
      dioxygen, (18)O2, and hydrogen peroxide, H2(18)O2, confirm that an oxygen atom is
      transferred directly from the H2(18)O2 oxidant to the olefin substrate in the
      predominant pathway. The hydrogen peroxide adduct of this high-oxidation-state
      manganese complex, Mn(IV)(Me2EBC)(O)(OOH)+, was detected by mass spectra in
      aqueous solutions prepared from Mn(II)(Me2EBC)Cl2 and excess hydrogen peroxide. A
      Lewis acid pathway, in which oxygen is transferred to the olefin from that
      adduct, Mn(IV)(Me2EBC)(O)(OOH)+, is proposed for epoxidation reactions mediated
      by this novel, non-heme manganese complex. A minor radical pathway is also
      apparent in these systems.

PMID- 16602809
TI  - Foreword. After the tsunami: mental health challenges to the community for today
      and tomorrow.

PMID- 16602810
TI  - The extent and impact of mental health problems after disaster.
AB  - Disasters are events that challenge the individual's ability to adapt, which
      carries the risk of adverse mental health outcomes including serious
      posttraumatic psychopathologies. While risk is related to degree of exposure to
      psychological toxins, the unique vulnerabilities of special populations within
      the affected community as well as secondary stressors play an important role in
      determining the nature and amount of morbidity. Disasters in developing countries
      and those associated with substantial community destruction are associated with
      worse outcome. Although acute responses are ubiquitous, few disasters lead to
      posttraumatic psychopathology in the majority of people exposed. However, the
      shortage of human resources in psychiatry, particularly in developing countries,
      places a considerable burden on psychiatric services even without the additional
      constraints imposed by disaster. Hence, disasters are events that invite a public
      health approach to mental health that better serves the needs of the individual
      and the affected community. Such an approach considers all available human
      resources and is intended to mitigate the effects of disaster before serious
      psychopathologic sequelae arise. This community mental health strategy allows
      peripheral mental health workers to mediate between survivors and specialized
      mental health professionals while assisting in removing barriers to treatment. To
      be effective when disaster occurs, this approach requires careful planning in
      conjunction with community consultation before implementation of formal disaster
      mitigation policies.

PMID- 16602811
TI  - Symptomatology and psychopathology of mental health problems after disaster.
AB  - A variety of reactions are observed after a major trauma. In the majority of
      cases these resolve without any long-term consequences. In a significant
      proportion of individuals, however, recovery may be impaired, leading to long
      term pathological disturbances. The most common of these is post-traumatic stress
      disorder (PTSD), which is characterized by symptoms of reexperiencing the trauma,
      avoidance and numbing, and hyperarousal. A range of other disorders may also be
      seen after trauma, and there is considerable overlap between PTSD symptoms and
      several other psychiatric conditions. Risk factors for PTSD include severe
      exposure to the trauma, female sex, low socioeconomic status, and a history of
      psychiatric illness. Although PTSD may resolve in the majority of cases, in some
      cases risk factors outweigh protective factors, and symptoms may persist for many
      years. PTSD often coexists with other psychiatric disorders, such as depression,
      anxiety disorders, and substance abuse, and with physical (somatization)
      symptoms. There is growing evidence that PTSD does not merely represent a normal
      response to stress, but rather is mediated by specific neurobiological
      dysfunctions.

PMID- 16602812
TI  - Practical assessment and evaluation of mental health problems following a mass
      disaster.
AB  - Almost all individuals who experience a severe trauma will develop symptoms of
      posttraumatic stress disorder (PTSD) shortly after the traumatic event. Although
      the natural history of PTSD varies according to the type of trauma, most people
      do not develop enduring PTSD, and, in many of those who do, it resolves within 1
      year without treatment. To the extent that is possible, maintenance of normal
      daily activities is believed to help patients cope more successfully in the
      aftermath of major trauma. In the case of a disaster such as the Asian tsunami,
      the whole community is involved, and it is impossible to continue with normal
      daily activities. To improve overall outcome after trauma, it would be optimal to
      identify individuals at increased risk for developing PTSD. This article
      describes screening and assessment tools for posttrauma mental health problems,
      particularly PTSD, and examines in more detail instruments that can be used in
      rapid field assessment of individuals who may be affected or who have already
      been identified and require monitoring. Self-rated instruments are most
      appropriate, but the choice of instrument will depend on the local situation and
      availability of appropriately validated questionnaires. The article also
      addresses important aspects of training nonmedical personnel in screening and
      assessment.

PMID- 16602813
TI  - Pharmacologic treatment of acute and chronic stress following trauma: 2006.
AB  - This article reviews pharmacologic treatment options for posttraumatic stress
      disorder (PTSD), focusing on goals of pharmacotherapy and the clinical trial
      evidence for drug treatments available for PTSD. The selective serotonin reuptake
      inhibitors (SSRIs) are recommended as first-line therapy for PTSD; the roles of
      these and other drug classes including anticonvulsants, mood enhancers, atypical
      antipsychotic agents, benzodiazepines, alpha1-adrenergic antagonists, and beta
      blockers in achieving improvement in PTSD symptom and outcome scores, achieving
      remission, and avoiding relapse are discussed. Treatment of PTSD in association
      with other comorbid conditions is addressed, and the role of pharmacotherapy in
      treating early PTSD and acute stress disorder is examined. Dosing strategies for
      the SSRIs sertraline and paroxetine are provided, and an algorithm for PTSD
      pharmacotherapy is discussed.

PMID- 16602814
TI  - Psychosocial therapy for posttraumatic stress disorder.
AB  - Immediately after experiencing a traumatic event, many people have symptoms of
      posttraumatic stress disorder (PTSD). If trauma victims restrict their routine
      and systematically avoid reminders of the incident, symptoms of PTSD are more
      likely to become chronic. Several clinical studies have shown that programs of
      cognitive-behavioral therapy (CBT) can be effective in the management of patients
      with PTSD. Prolonged exposure (PE) therapy-a specific form of exposure therapy
      can provide benefits, as can stress inoculation training (SIT) and cognitive
      therapy (CT). PE is not enhanced by the addition of SIT or CT. PE therapy is a
      safe treatment that is accepted by patients, and benefits remain apparent after
      treatment programs have finished. Nonspecialists can be taught to practice
      effective CBT. For the treatment of large numbers of patients, or for use in
      centers where CBT has not been routinely employed previously, appropriate
      training of mental health professionals should be performed. Methods used for the
      dissemination of CBT to nonspecialists need to be modified to meet the
      requirements of countries affected by the Asian tsunami. This will entail the use
      of culturally sensitive materials and the adaptation of training methods to
      enable large numbers of mental health professionals to be trained together.

PMID- 16602815
TI  - Assessment of resilience in the aftermath of trauma.
AB  - Resilience is a crucial component in determining the way in which individuals
      react to and deal with stress. A broad range of features is associated with
      resilience; these features relate to the strengths and positive aspects of an
      individual's mental state. In patients with posttraumatic stress disorder,
      resilience can be used as a measure of treatment outcome, with improved
      resilience increasing the likelihood of a favorable outcome. Resilience can be
      monitored using the Connor-Davidson Resilience Scale, and perceived vulnerability
      to the effects of stress can be monitored with the Sheehan Stress Vulnerability
      Scale. Both scales are well validated, self-rated, easy to use, and easily
      translatable. Within a short period of time, nonspecialists can be taught to use
      these in the field.

PMID- 16602816
TI  - Recovery after the tsunami: timeline for rehabilitation.
AB  - In the aftermath of the Asian tsunami, there is potentially a large, traumatized
      population in need of psychosocial support, but determining which individuals
      require psychological intervention and knowing how and when to treat them may be
      the key to positive long-term outcomes. The early identification of people at
      high risk of developing subsequent psychiatric disorders from among those
      experiencing a transient stress reaction following trauma is often the initial
      step in the recovery process. Clinical instruments for screening and/or
      predicting those most at risk are available and require validating for cultural
      and linguistic sensitivity. Timely treatment is essential, since inappropriately
      targeted therapy can compromise recovery and may even exacerbate posttraumatic
      stress symptoms, particularly if treatment is initiated before grief reactions
      have subsided. Finally, appropriate treatment interventions, which incorporate
      cognitive-behavioral therapy and prolonged exposure, offer the best current
      therapeutic options for the treatment of posttraumatic stress disorder and
      associated comorbid conditions such as anxiety, depression, and grief. However,
      since most of the supportive data for the psychosocial consequences of trauma
      were obtained from small-scale studies of discrete trauma events in Western
      countries, it may not be possible to extrapolate these findings to a large-scale
      natural disaster in Asia, such as the Asian tsunami. More data are required to
      assist in the development of strategies for the effective management of the
      psychological consequences of trauma worldwide, with emphasis on creating mental
      health strategies that are culturally sensitive and valid for various trauma
      events and disaster scenarios.

PMID- 16602817
TI  - Lessons in posttraumatic stress disorder from the past: Venezuela floods and
      Nairobi bombing.
AB  - Identification and treatment of posttraumatic stress disorder (PTSD) are
      important following a disaster. Insights into how these aims can be achieved may
      be obtained from previous disasters. This article describes mental health
      initiatives following the 1999 flooding in Vargas State, Venezuela, and the 1998
      U.S. Embassy bombing in Nairobi, Kenya. Following the Vargas State floods, a
      specialist mental health center devoted to the diagnosis, treatment, and follow
      up of PTSD was established. Awareness and acceptance of the clinic was promoted
      by media campaigns and community-based activities. After 18 months, approximately
      5000 people had been screened, of whom 62% were diagnosed with PTSD and treated.
      Moreover, the clinic's activities had expanded to include treatment of other
      medical conditions and assistance with nonmedical needs. Following the Nairobi
      bombing, a mass media campaign was initiated to create awareness of PTSD symptoms
      and help victims come to terms with their experience. This campaign was found to
      be well received and helpful. In addition, counselors were trained to support
      people living or working close to the blast. These examples show that mental
      health initiatives are feasible after a disaster and highlight a number of
      issues: (1) The intervention should be tailored to the needs of the target
      population; (2) Communication should be simple and appropriate; (3) Community
      based activities are valuable in promoting awareness and acceptance of mental
      health initiatives; (4) Reducing the stigma often associated with mental health
      problems is important; and (5) The mass media can be helpful in promoting
      awareness of mental health issues following major trauma.

PMID- 16602818
TI  - Management of trauma in special populations after a disaster.
AB  - Special populations are particularly vulnerable to mental health problems in the
      aftermath of a disaster. Efficient delivery of mental health services, the
      integrated use of psychosocial services and mental health facilities, and the
      active intervention of trained community health care workers can offer effective
      management of the psychosocial problems of special populations. Women, children,
      adolescents, the poor, the elderly, and individuals with preexisting health
      problems have been identified as special populations who often suffer
      psychological morbidity as a result of a catastrophic disaster. Understanding the
      cultural, ethnic, and socioeconomic factors in a postdisaster situation is
      crucial to helping special populations overcome debilitating mental illness and
      declining quality of life. Planning the delivery of mental health services is
      critical and includes hazard mapping to identify vulnerable geographic and social
      areas, screening instruments to identify at-risk populations, and education of
      community leaders and health care workers. An integrated approach using
      psychosocial and institutionalized interventions can provide better outcomes than
      either approach alone. A community-based approach with trained grassroots health
      care workers can provide effective psychosocial support and rehabilitation
      services.

PMID- 16602819
TI  - Cultural sensitivity: making trauma assessment and treatment plans culturally
      relevant.
AB  - The Asian tsunami on December 26, 2004, has had a profound impact on the mental
      health of large numbers of people in several South Asian nations. Many
      psychological interventions with relevance to this disaster have been shown to be
      effective in a Western context. For these psychological interventions to prove
      effective in the tsunami-affected regions, they must be understood and accepted
      by health-care practitioners and patients in their individual cultural settings
      and must be adapted to these settings on the basis of careful dialogue between
      health-care professionals, community and religious leaders, and patients.
      Religious, socioeconomic, and other cultural influences all affect the
      acceptability and success of various psychological assessment and treatment
      tools. The cultural specificity of these tools needs careful validation in the
      tsunami-affected countries. The challenge in each local situation is to find the
      optimal means of adapting tools such as cognitive-behavioral therapy into
      appropriate strategies for local communities. We advocate a culturally sensitive
      approach to ensure that the impact of interventions is optimized to benefit the
      communities recovering from such a traumatic disaster.

PMID- 16602820
TI  - Plasticity of the cis-regulatory input function of a gene.
AB  - The transcription rate of a gene is often controlled by several regulators that
      bind specific sites in the gene's cis-regulatory region. The combined effect of
      these regulators is described by a cis-regulatory input function. What determines
      the form of an input function, and how variable is it with respect to mutations?
      To address this, we employ the well-characterized lac operon of Escherichia coli,
      which has an elaborate input function, intermediate between Boolean AND-gate and
      OR-gate logic. We mapped in detail the input function of 12 variants of the lac
      promoter, each with different point mutations in the regulator binding sites, by
      means of accurate expression measurements from living cells. We find that even a
      few mutations can significantly change the input function, resulting in functions
      that resemble Pure AND gates, OR gates, or single-input switches. Other types of
      gates were not found. The variant input functions can be described in a unified
      manner by a mathematical model. The model also lets us predict which functions
      cannot be reached by point mutations. The input function that we studied thus
      appears to be plastic, in the sense that many of the mutations do not ruin the
      regulation completely but rather result in new ways to integrate the inputs.

PMID- 16602821
TI  - BGEM: an in situ hybridization database of gene expression in the embryonic and
      adult mouse nervous system.

PMID- 16602822
TI  - Keeping tabs on the women: life scientists in Europe.

PMID- 16602824
TI  - Offline persistence of memory-related cerebral activity during active
      wakefulness.
AB  - Much remains to be discovered about the fate of recent memories in the human
      brain. Several studies have reported the reactivation of learning-related
      cerebral activity during post-training sleep, suggesting that sleep plays a role
      in the offline processing and consolidation of memory. However, little is known
      about how new information is maintained and processed during post-training
      wakefulness before sleep, while the brain is actively engaged in other cognitive
      activities. We show, using functional magnetic resonance imaging, that brain
      activity elicited during a new learning episode modulates brain responses to an
      unrelated cognitive task, during the waking period following the end of training.
      This post-training activity evolves in learning-related cerebral structures, in
      which functional connections with other brain regions are gradually established
      or reinforced. It also correlates with behavioral performance. These processes
      follow a different time course for hippocampus-dependent and hippocampus
      independent memories. Our experimental approach allowed the characterization of
      the offline evolution of the cerebral correlates of recent memories, without the
      confounding effect of concurrent practice of the learned material. Results
      indicate that the human brain has already extensively processed recent memories
      during the first hours of post-training wakefulness, even when simultaneously
      coping with unrelated cognitive demands.

PMID- 16602823
TI  - Testing electrostatic complementarity in enzyme catalysis: hydrogen bonding in
      the ketosteroid isomerase oxyanion hole.
AB  - A longstanding proposal in enzymology is that enzymes are electrostatically and
      geometrically complementary to the transition states of the reactions they
      catalyze and that this complementarity contributes to catalysis. Experimental
      evaluation of this contribution, however, has been difficult. We have
      systematically dissected the potential contribution to catalysis from
      electrostatic complementarity in ketosteroid isomerase. Phenolates, analogs of
      the transition state and reaction intermediate, bind and accept two hydrogen
      bonds in an active site oxyanion hole. The binding of substituted phenolates of
      constant molecular shape but increasing pK(a) models the charge accumulation in
      the oxyanion hole during the enzymatic reaction. As charge localization
      increases, the NMR chemical shifts of protons involved in oxyanion hole hydrogen
      bonds increase by 0.50-0.76 ppm/pK(a) unit, suggesting a bond shortening of 0.02
      A/pK(a) unit. Nevertheless, there is little change in binding affinity across a
      series of substituted phenolates (DeltaDeltaG = -0.2 kcal/mol/pK(a) unit). The
      small effect of increased charge localization on affinity occurs despite the
      shortening of the hydrogen bonds and a large favorable change in binding enthalpy
      (DeltaDeltaH = -2.0 kcal/mol/pK(a) unit). This shallow dependence of binding
      affinity suggests that electrostatic complementarity in the oxyanion hole makes
      at most a modest contribution to catalysis of 300-fold. We propose that
      geometrical complementarity between the oxyanion hole hydrogen-bond donors and
      the transition state oxyanion provides a significant catalytic contribution, and
      suggest that KSI, like other enzymes, achieves its catalytic prowess through a
      combination of modest contributions from several mechanisms rather than from a
      single dominant contribution.

PMID- 16602825
TI  - Money for nothing? A call for empirical evaluation of biodiversity conservation
      investments.

PMID- 16602826
TI  - Lipoprotein genotype and conserved pathway for exceptional longevity in humans.
AB  - Alteration of single genes involved in nutrient and lipoprotein metabolism
      increases longevity in several animal models. Because exceptional longevity in
      humans is familial, it is likely that polymorphisms in genes favorably influence
      certain phenotypes and increase the likelihood of exceptional longevity. A group
      of Ashkenazi Jewish centenarians (n = 213), their offspring (n = 216), and an age
      matched Ashkenazi control group (n = 258) were genotyped for 66 polymorphisms in
      36 candidate genes related to cardiovascular disease (CVD). These genes were
      tested for association with serum lipoprotein levels and particle sizes,
      apolipoprotein A1, B, and C-3 levels and with outcomes of hypertension, insulin
      resistance, and mortality. The prevalence of homozygosity for the -641C allele in
      the APOC3 promoter (rs2542052) was higher in centenarians (25%) and their
      offspring (20%) than in controls (10%) (p = 0.0001 and p = 0.001, respectively).
      This genotype was associated with significantly lower serum levels of APOC3 and a
      favorable pattern of lipoprotein levels and sizes. We found a lower prevalence of
      hypertension and greater insulin sensitivity in the -641C homozygotes, suggesting
      a protective effect against CVD and the metabolic syndrome. Finally, in a
      prospectively studied cohort, a significant survival advantage was demonstrated
      in those with the favorable -641C homozygote (p < 0.0001). Homozygosity for the
      APOC3 -641C allele is associated with a favorable lipoprotein profile,
      cardiovascular health, insulin sensitivity, and longevity. Because modulation of
      lipoproteins is also seen in genetically altered longevity models, it may be a
      common pathway influencing lifespan from nematodes to humans.

PMID- 16602828
TI  - How do neurons look at the world?

PMID- 16602827
TI  - Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending
      on receptor context.
AB  - The Wnts comprise a large class of secreted proteins that control essential
      developmental processes such as embryonic patterning, cell growth, migration, and
      differentiation. In the most well-understood "canonical" Wnt signaling pathway,
      Wnt binding to Frizzled receptors induces beta-catenin protein stabilization and
      entry into the nucleus, where it complexes with T-cell factor/lymphoid enhancer
      factor transcription factors to affect the transcription of target genes. In
      addition to the canonical pathway, evidence for several other Wnt signaling
      pathways has accumulated, in particular for Wnt5a, which has therefore been
      classified as a noncanonical Wnt family member. To study the alternative
      mechanisms by which Wnt proteins signal, we purified the Wnt5a protein to
      homogeneity. We find that purified Wnt5a inhibits Wnt3a protein-induced canonical
      Wnt signaling in a dose-dependent manner, not by influencing beta-catenin levels
      but by downregulating beta-catenin-induced reporter gene expression. The Wnt5a
      signal is mediated by the orphan tyrosine kinase Ror2, is pertussis toxin
      insensitive, and does not influence cellular calcium levels. We show that in
      addition to its inhibitory function, Wnt5a can also activate beta-catenin
      signaling in the presence of the appropriate Frizzled receptor, Frizzled 4. Thus,
      this study shows for the first time that a single Wnt ligand can initiate
      discrete signaling pathways through the activation of two distinct receptors.
      Based on these and additional observations, we propose a model wherein receptor
      context dictates Wnt signaling output. In this model, signaling by different Wnt
      family members is not intrinsically regulated by the Wnt proteins themselves but
      by receptor availability.

PMID- 16602829
TI  - Genetic, age and light mediated effects on crystallin protein expression in the
      retina.
AB  - To probe for possible relationships between retinal crystallins and retinal
      degenerations, protein expression was compared in normal Sprague-Dawley rats,
      treated or not with intense light, Royal College of Surgeons (RCS) rats and
      transgenic rats expressing rhodopsin mutations. Rats were reared in dim cyclic
      light for 21-75 days. Photoreceptor cell DNA levels were determined at various
      ages to assess the rates of visual cell loss. 1D- and 2D-gel electrophoresis was
      used to profile retinal protein expression. Crystallins were identified by
      western analysis and by tandem mass spectrometry. In normal rat retinas, alpha,
      beta and gamma crystallins were present, although alphaA- and gamma-crystallins
      exhibited some increase with age. As measured by DNA levels, the rate of
      genetically induced photoreceptor cell loss was greater in rats with faster
      degenerating retinas (RCS, S334-ter Line 4, P23H Line 3) than in rats with slower
      degenerating retinas (S334-ter Line 9, P23H Line 2). In genetic models of retinal
      degeneration increased levels of immunoreactivity for all crystallins, especially
      alphaA-insert, correlated with the different rates of photoreceptor loss. In the
      light induced degeneration model alphaA-insert was unchanged, truncated alphaB
      crystallin levels were increased and gamma-crystallins were greatly reduced. In
      the RCS rat retina 16 different crystallins were identified. Our data suggests
      that an increase in crystallin expression occurs during various retinal
      degenerations and that the increases may be related to the severity, type and
      onset of retinal degeneration.

PMID- 16602830
TI  - Ecotoxicological effects of combined UVB and organic contaminants in coastal
      waters: A review.
AB  - Organisms living in coastal waters are exposed to anthropogenic contaminants from
      terrestrial drainage, ice melting and maritime traffic and to enhanced UVB
      radiation (UVBR; 280-320 nm) caused by decreased concentrations of ozone in the
      stratosphere. This article reviews available information about the combined
      effects of UVBR and selected hydrosoluble contaminants potentially present in
      surface waters on marine species and especially on plankton community structure
      in high-latitude coastal zones. Effects of UVBR on three selected pesticides
      (Atrazine, carbaryl and Acifluorfen) and possible induction of phototoxicity are
      reviewed. Most toxicological studies have been conducted under laboratory
      conditions with questionable relevance for coastal marine ecosystems. Similarly,
      photoactivation of polycyclic aromatic hydrocarbons (PAHs) has been closely
      examined and reported effects on aquatic species summarized. Experiments with
      field-sampled communities demonstrated the complexity and the difficulty in
      determining the impact of multiple stressors on an aquatic ecosystem, even for
      ecosystems simplified by eliminating large grazers and fish. Nutrient status,
      specific composition and light history have influenced the different responses of
      planktonic assemblages exposed to enhanced UVBR and water-soluble fraction (WSF)
      from crude oil or to tributyltin. Plankton assemblages subjected to changes in
      the ozone hole were physiologically stressed and more susceptible to WSF toxicity
      than communities from less enhanced UVBR-impacted sites. A close relationship
      between phytoplankton assemblages and bacteria was observed in all experiments in
      mesocosms. A contaminant-induced phytoplankton crash after a bloom event may
      release important carbon and nutrient sources for bacteria. The magnitude of
      phytoplanktonic mortality induced by a contaminant probably influenced how
      rapidly bacteria grew over time. The transition from a herbivorous food web to a
      microbial food web has significant ecological implications for carbon cycling and
      energy flow in pelagic systems. A high phytoplankton mortality implies a
      situation in which the potential for downward carbon export from surface waters
      is high. In contrast, high bacterial enrichment implies that the phytoplankton
      carbon is largely recycled in surface waters through a microbial loop and does
      not contribute significantly to sinking particle flux. The most ecologically
      relevant results were obtained with mesocosm studies using field-collected
      communities. The enhancement of hydrocarbon toxicity in the presence of a high
      level of UVBR cannot be described as being a synergistic or an additive effect,
      because the WSF alone is not toxic and may even be beneficial by increasing
      bacterial activity. This is a case in which one stressor has the ability to
      modify another stressor to cause it to be toxic to target organisms. These
      abiotically induced interactions may be important for biological communities
      exposed to extreme conditions when physical, chemical or photochemical reactions
      modify the nature of environmental stressors before they interact with biological
      functions. The need for models on the impacts of multiple stressors on
      biodiversity and ecosystem functioning is emphasized.

PMID- 16602834
TI  - The protonated Schiff base of halorhodopsin from Natronobacterium pharaonis is
      hydrolyzed at elevated temperatures.
AB  - Halorhodopsin from Natronobacterium pharaonis (pHR) is a light-driven chloride
      pump in which photoisomerzation of a retinal chromophore triggers a photocycle
      which leads to a chloride anion transport across the plasma membrane. Similarly
      to other retinal proteins the protonated Schiff base (PSB), which covalently
      links the retinal to the protein, does not experience hydrolysis reaction at room
      temperature even though several water molecules are located in the protonated
      Schiff base (PSB) vicinity. In the present studies we have revealed that in
      contrast to other studied archaeal rhodopsins, temperature increase to about 70
      degrees C hydrolyses the PSB linkage of pHR. The rate of the reaction is affected
      by Cl-concentration and reveals an anion binding site (in addition to the Cl- in
      the SB vicinity) with a binding constant of 100mM (measured at 70 degrees C). We
      suggest that this binding site is located on the extracellular side and its
      possible role in the Cl-pumping mechanism is discussed. The rate of the
      hydrolysis reaction is affected by the nature of the anion bound to pHR.
      Substitution of the Cl- anion by Br-, I- and SCN- exhibits similar behavior to
      that of CI- in the region of 100mM but higher concentrations are needed for N3-,
      HCOO- and NO2-to achieve similar behavior. Steady state pigment illumination
      accelerates the reaction and reduces the energy of activation and the frequency
      factor. Adjusting the sample temperature to 25 degrees C following the hydrolysis
      reaction led to about 80% pigment recovery. However, the newly reformed pigment
      is different from the mother pigment and has different characteristics. It is
      concluded that the apo-membrane adopts a modified conformation and/or aggregated
      state which rebinds the retinal to give a new conformation of the pHR pigment.

PMID- 16602835
TI  - Participatory supervision model: building health promotion capacity among health
      officers and the community.
AB  - INTRODUCTION: The Thai traditional health supervision model has been developed
      since 1991. However, many supervisors lack supervisory knowledge and skills. This
      study aimed to compare and identify the strengths and challenges of two different
      supervision models, in order to determine their effects on enhancing the health
      promotion capacity of health officers in two primary care units (PCU) in Chiang
      Mai Province, northern Thailand. METHODS: The two models were implemented at two
      PCU in one semi-district, Chiang Mai Province, over a six-month period. The first
      model involved supervisors from the district level, with the full participation
      of health officers at the sub-district level. The second model was designed with
      the addition of community involvement in the supervision process. Before
      implementing the models, the district supervisors attended a retraining course to
      enhance their supervisory knowledge and ability. Questionnaires were used to
      assess health officers' job satisfaction, clients' perceived service quality and
      care satisfaction. Semi-structured interviews and qualitative observations were
      used to explore the involvement of health officers and the community, and to
      determine the strengths and challenges of each supervisory model. RESULTS: Both
      before and after the intervention, the PCU health officers appeared to have good
      and comparable job satisfaction levels. Bivariate analysis indicated that after
      the intervention, both supervisory models appeared effective in terms of clients'
      perceived service quality and satisfaction with care, among those who utilized
      the PCU. However, the second model, which allowed the community to participate in
      the supervision process, achieved better results. The qualitative findings
      suggested that the involvement of health officers caused a rapid change and
      improvement after the supervision. The involvement of the community helped the
      community itself to identify problems and formulate alternatives to meet the
      community's needs. CONCLUSIONS: This study shows positive outcomes for two forms
      of participatory supervision in a rural setting. There appear to be additional
      positive outcomes for the model that involved community participation. To ensure
      successful implementation, several issues, such as the supervisor's knowledge and
      ability, health officer workload and supervisory communication skills, need to be
      improved.

PMID- 16602837
TI  - The chemical erosion of human health: adverse environmental exposure and in-utero
      pollution - determinants of congenital disorders and chronic disease.
AB  - Epidemiological research designed to explore causality of illness has produced
      increasing evidence to verify that exposure to toxic agents is contributing to
      the escalating burden of chronic affliction, including congenital disorders.
      While endeavoring to facilitate optimal health and well-being for patients, the
      medical profession is currently challenged by the consequences of environmental
      factors unique to the modern era. In the last half century, there have been
      profound shifts in health-related habits of individuals and population groups,
      and recent research suggests that changes in the home and workplace environment
      are responsible for many common health problems including various congenital
      anomalies. As a result of increasing concern about environmental influences on
      health, 'Human Exposure Assessment,' the investigation and study of specific
      patient exposures and related health concerns, is a rapidly expanding area of
      scientific research. Practitioners of clinical medicine, including providers of
      maternity care, should acquire the skills to elicit a proper environmental
      exposure history and the necessary tools to implement proactive patient education
      relating to precautionary avoidance.

PMID- 16602836
TI  - Diet, nutritional status and food related traditions of Oraon tribes of New Mal
      (West Bengal), India.
AB  - INTRODUCTION: According to the 2001 census conducted by the Government of India,
      India has more than 84 million tribals who constitute 8.2% of India's population.
      The Oraons are an agricultural tribe found mainly in Orissa, Bihar, Jharkhand and
      West Bengal. The present study was undertaken on a group of Oraon tribals working
      in a tea gardens of New Mal in Jalpaiguri district of West Bengal. The children
      attended the local primary school. The Oraons are covered by the Integrated Child
      Development Scheme (ICDS) of the Government of India, which is concerned with the
      health, nutrition and development of children and their mothers. To evaluate the
      effect of ICDS, the practices of adults towards hygiene, medication, addictive
      substances and diet were also recorded. METHODS: 500 Oraon tribals, including 200
      men and 150 women aged 20-45 years, and 150 children aged 6-12 years, were
      surveyed for their dietary intake by 24-hour recall and semi-quantitative food
      frequency questionnaire methodology and anthropometry, and a description of food
      related traditions. RESULTS: The diet of all Oraon groups was deficient in all
      food groups. Cereal intake was least deficient, while the intake of milk and
      fruit was almost negligible. Their diet was supplemented by a locally grown green
      leafy vegetable dheki saag, and fermented leftover rice. The energy available
      from the diet for all age groups was only 52-53% of the recommended dietary
      allowances of the Indian Council of Medical Research. Children were enrolled in a
      midday meal program at the local primary school; however, their energy intake was
      severely deficient, and of the same order as their parents. The mean basal mass
      index (BMI) of adult Oraons was not low, but children were severely
      undernourished. Men were less undernourished than were women. Some potentially
      useful traditions practiced included wiping washed utensils with leaves of a
      local plant mirchaiya, preparing herbal tablets called ranoodava to make an
      alcoholic and a medicinal drink called hadiya. The Oraons' knowledge of
      contraception, vaccinations, proper diet and supplements needed for successful
      pregnancy was severely deficient. CONCLUSIONS: A remarkable finding of this study
      on the Oraon tribals is that the BMI of children was substantially below that of
      adult men and women. This deficiency cannot be attributed to energy intake
      because energy intake of children, as percentage of recommended dietary
      allowance, was about the same as adults. The study shows that the midday meal
      program provided only approximately 25% of the energy requirements of the
      children; moreover, it was qualitatively deficient. It also seems that the midday
      meal replaced rather than supplemented home meals. Despite ICDS coverage,
      knowledge with regard to contraception, vaccinations, proper diet and supplements
      needed for successful pregnancy was very low. Interesting traditional practices
      concerned with methods of preparing food and use of local plants as medicines
      were observed and documented. Rural health professionals should ensure adequate
      quantity and quality of food supplementation. They should strive to disseminate
      health related knowledge. Traditional tribal practices should be studied for
      their nutritional and medicinal value. They could be responsible for the adequate
      BMI of adult Oraon, despite severe deficiency in energy intake.

PMID- 16602838
TI  - Cesarean section in term breech presentations: do rates of adverse neonatal
      outcomes differ by hospital birth volume?
AB  - AIM: To determine if risk of adverse neonatal outcomes among term breech infants
      delivered by cesarean section differs by volume of such births at the delivering
      hospital. METHODS: We conducted a population-based cohort study using Missouri
      linked birth and death certificate files. The study population included 10,106
      singleton, term, normal birth weight infants in breech presentation delivered by
      cesarean section. Infants were linked to hospitals where delivered. These
      hospitals were divided into terciles (low, medium, and high volume) based on the
      median number of annual deliveries during 1993-1999. The primary outcome was
      presentation of at least one adverse neonatal outcome. Adjusted odds ratios and
      95% confidence intervals (CI) were calculated using logistic regression analysis.
      RESULTS: The rate of any adverse outcome was 17.8, 15.0, and 5.9 cases per 1,000
      deliveries at low-, medium-, and high-volume hospitals, respectively. All
      component adverse outcomes occurred more frequently in low- or medium-volume
      hospitals than in high-volume hospitals. Compared to breech infants delivered at
      high-volume hospitals, those delivered at low-volume and medium-volume hospitals
      were 2.7 (CI 1.6, 4.5) and 2.4 (CI 1.4, 4.1) times, respectively, more likely to
      experience an adverse outcome after adjusting for significant confounders.
      CONCLUSIONS: Prospective studies should explore the source of these risk
      differences.

PMID- 16602839
TI  - Antibiotic therapy for preterm premature rupture of membranes - results of a
      multicenter study.
AB  - AIMS: To evaluate whether primary application of mezlozillin in preterm premature
      rupture of membranes (pPROM) prolongs pregnancy and lowers neonatal morbidity.
      METHODS: In this prospective, randomized, double blind, placebo-controlled
      multicenter study a total of 105 pregnant women with pPROM between 24 + 0 and 32
      + 6 weeks of gestation were examined receiving i.v. injections of corticoids and
      tocolytics as well as mezlocillin (3 x 2 g/d) or placebo. Assessed factors were
      prolongation of pregnancy and neonatal morbidity such as neonatal infection,
      respiratory distress syndrome (RDS), intraventricular hemorrhage (IVH) and
      necrotizing enterocolitis (NEC). RESULTS: Prolongation of pregnancy by more than
      7 days was achieved in 63.8% of the mezlocillin group versus 44.8% of the placebo
      group (P < 0.05). The babies of mothers treated with anibiotics had fewer
      neonatal infections, RDS, IVH and NEC. Total morbidity was significantly lowered
      in the verum group (P = 0.02). CONCLUSIONS: Antibiotic administration following
      preterm premature rupture of membranes is associated with a prolongation of
      pregnancy and a reduction of neonatal infectious morbidity.

PMID- 16602840
TI  - Relation between grief and subsequent pregnancy status 13 months after perinatal
      bereavement.
AB  - AIMS: The present longitudinal study sought to explore the relationship between
      parental grief following perinatal bereavement and subsequent pregnancy,
      according to the particular facets of grief and pregnancy state being considered.
      METHOD: The study participants were 63 couples who had been bereaved by
      stillbirth (n = 31) or neonatal death (n = 32). The relationship of self-reported
      grief (Perinatal Grief Scale-33 Active Grief, Difficulty Coping and Despair) 1
      month and 13 months after the loss to subsequent pregnancy status (Pregnant, n =
      20, Live Baby, n = 10, Trying, n = 11, Not Trying, n = 22) at 13 months was
      investigated with repeated measures analysis of variance. RESULTS: There were
      statistically significant main effects for Active Grief and Difficulty Coping in
      women and men and Despair in women, but not in men. There was a statistically
      significant Active Grief by pregnancy status interaction in women (F(3, 59) =
      2.89, P = 0.04), but not in men. Simple main effects analysis indicated a
      statistically significant decrease in Active Grief in women who were pregnant
      (F(1, 59) = 52.8, P < 0.0005), women who were not pregnant and not trying to
      conceive (F(1, 59) = 27.5, P < 0.0005), and women who had had a live baby (F(1,
      59) = 9.62, P = 0.003). There was no statistically significant decrease in Active
      Grief in women who were not pregnant but trying to conceive (F(1, 59) = 3.44, P =
      0.07). The Difficulty Coping in women and men and Despair in women by pregnancy
      status interactions were not statistically significant. None of the between
      subjects main effects for pregnancy status was statistically significant in women
      or men. CONCLUSION: The relation between grief and subsequent pregnancy differed
      with the sex of the parent and the particular facets of grief and pregnancy state
      being considered. Subsequent pregnancy was related to Active Grief in women, but
      not to Difficulty Coping or Despair that are known to be predictors of chronic
      grief.

PMID- 16602841
TI  - Vaginal birth after cesarean section: X-ray pelvimetry at term is informative.
AB  - OBJECTIVE: To examine whether X-ray pelvimetry data to evaluate the likelihood of
      vaginal birth after previous cesarean section. DESIGN: Retrospective study.
      SETTING: University hospital. POPULATION: Patients with a previous cesarean
      delivery who underwent X-ray pelvimetry and gave birth at gestational age 37
      weeks during a seven-year period. METHODS: 1190 patients with a scarred uterus
      were compared with 15,189 patients without a scarred uterus. In the scarred
      uterus group, 760 patients with a transverse pelvic diameter > or =12 cm were
      compared with 430 patients with a transverse pelvic diameter <12 cm. MAIN OUTCOME
      MEASURES: The obstetrical outcomes were spontaneous or induced labor, and mode of
      delivery. The maternal morbidity outcomes were hemorrhage requiring transfusion
      of packed red cells, uterine rupture, bladder injury, and hysterectomy due to
      hemorrhage. The neonatal morbidity outcomes were the 5-min Apgar score, transfer
      to intensive care, and intubation. RESULTS: Patients with a scarred uterus had a
      significantly higher rate of cesarean section (35.5%) than those with no prior
      cesarean section (9%). Among patients with a scarred uterus who were selected for
      vaginal delivery, 81% delivered vaginally when the transverse diameter (TD) of
      the pelvic inlet was greater than 12 cm, 68% when the TD was between 11.5 and 12
      cm, and 58% when the TD was less than 11.5 cm. Maternal morbidity was
      significantly higher in the patients with a scarred uterus. The neonatal results
      were comparable in the different groups. CONCLUSION: X-ray pelvimetry tailors the
      information given to each patient about the likelihood of having a vaginal
      delivery. It can also be used to optimize the selection of patients allowed to
      enter labor.

PMID- 16602842
TI  - Dilatation of the abdominal umbilical vein is associated with increased risk of
      thrombotic complications.
AB  - Malformations of the umbilical vein are rare abnormalities diagnosed on prenatal
      ultrasound. They might be associated with fetal hydrops and fetal death. We
      report two newborn infants with prenatal diagnosis of umbilical vein dilatation
      who developed venous thrombosis and discuss the pre- and postnatal management of
      the constellation with special emphasis on antithrombotic treatment.

PMID- 16602843
TI  - Retrospective diagnosis of hypoxic myocardial injury in premature newborns.
AB  - Perinatal asphyxia has a high impact on neonatal mortality, morbidity, and
      neurological outcome. The hypoxic effects on brain, kidney and gastrointestinal
      system are well recognized in newborns. While it is known that hypoxia also
      effects cardiac function, there are few studies of quantitative myocardial injury
      in premature infants who suffered hypoxia. AIM: To investigate usefulness of
      cardiac troponin (cTnT) and creatinine kinase MB (CK-MB) in the diagnosis of
      myocardial injury due to birth hypoxia and to correlate these markers with
      cardiac functions as measured by echocardiogram. METHODS: We studied 43 preterm
      infants: 21 with birth asphyxia and 22 controls. Echocardiographic studies and
      quantitative determination of cTnT and CK-MB in blood serum was performed between
      the 12(th) and the 24(th) h of life. RESULTS: cTnT and CK-MB levels were higher
      in asphyxiated infants compared to controls (0.287 +/- 0.190 vs. 0.112 +/- 0.099
      ng/mL, P < 0.001) and (18.35 +/-14.81 vs. 11.09 +/- 5.17 ng/L, P < 0.05). Among
      controls, we observed an elevated value of cTnT in those with respiratory
      distress syndrome (RDS). We found a decrease in fractional shortening (P < 0.05)
      and an increase in tricuspid insufficiency (P < 0.01) in asphyxiated newborns.
      CONCLUSIONS: cTnT and CK-MB levels are strong indicators of myocardial injury due
      to perinatal hypoxia. The cTnT level was most strongly related to RDS.

PMID- 16602844
TI  - Fetal brain injury in experimental intrauterine asphyxia and inflammation in
      Gottingen minipigs.
AB  - OBJECTIVE: To examine fetal brain injury in the Gottingen minipig following
      intrauterine asphyxia and infection/inflammation induced at 3/4 of gestational
      length. METHODS: We performed laparotomy after anesthesia in six pregnant sows.
      We randomized 29 fetuses to one of four groups: pretreatment with saline or
      endotoxin followed by 30 min of umbilical cord occlusion or no occlusion. After
      48 h we performed a re-laparotomy and examined the fetal brains. RESULTS: After
      total asphyxia, brain stem injury was present in the group pretreated with saline
      (P < 0.01 vs. controls) and with endotoxin (P < 0.005 vs. controls). Microglia
      activation was more marked in the brain stem (P < 0.05) and posterior white
      matter (P < 0.05) in the asphyxia group than in controls. Two of five fetuses in
      the asphyxia group had white matter injury, while no white matter lesions were
      found in the asphyxia/inflammation or endotoxin only groups. CONCLUSIONS: In this
      Gottingen minipig model, a species closer to humans than animals commonly used in
      experimental studies of perinatal brain injuries, intrauterine asphyxia following
      pretreatment with saline caused brain stem and white matter injury. This model
      can be further developed to study the impact of other intrauterine exposures on
      brain injury.

PMID- 16602845
TI  - Intrauterine growth restriction induces increased capillary density and
      accelerated type I fiber maturation in newborn pig skeletal muscles.
AB  - AIMS: Humans with low birth weight exhibit evidences of vascular dysfunction.
      Recent findings indicate a microvascular rarefaction in skeletal muscles soon
      after postnatal development in rats suffered by intrauterine protein restriction.
      METHODS: To examine the effects of intrauterine growth restriction on capillary
      density, muscle fiber distribution and accompanying muscular and systemic
      circulation immediately after birth, studies were conducted on 1-day-old
      anesthetized normal weight (n = 7) and intrauterine growth restricted (n = 6)
      piglets. Cardiac output and hind limb muscle blood flow were measured by colored
      microspheres. Counting of type I fibers and skeletal capillary numbers was done
      by immunohistochemical staining. RESULTS: Increased proportion of type I fibers
      and capillary density was found in the flexor digitalis superficialis and
      gastrocnemius medialis (P < 0.05) in newborn IUGR piglets. Furthermore, a marked
      correlation was shown between capillary density and type I fiber fraction for all
      flexor muscles studied (P < 0.05). Moreover, cardiac output and muscular blood
      flow were markedly increased in IUGR piglets (P < 0.05). Correspondingly, total
      peripheral resistance, as well as vascular resistance, of hind limb flexors
      appeared significantly decreased (P < 0.05). CONCLUSIONS: Compromised
      intrauterine environmental conditions leading to fetal growth restriction
      provokes coordinated structural and functional adaptation of skeletal muscles.

PMID- 16602846
TI  - Closing arguments for gastroschisis: management with silo reduction.
AB  - BACKGROUND: There are two approaches to close gastroschisis. Primary closure (PC)
      is reduction and fascial closure; silo closure (SC) places viscera in a preformed
      silo and reduces the contents over time. We have shifted from PC to SC. This
      study compared the outcomes of these two techniques. METHODS: Records of babies
      with gastroschisis from 1994-2004 were reviewed. Closure type, ventilator days,
      days to full-feeds, hospital days, complications, and mortality were recorded.
      RESULTS: Twenty-eight patients underwent PC; 20 patients had SC. Differences in
      ventilator days, days to full-feeds, and hospital days were not statistically
      significant. Nine PC patients developed closure-related complications vs. none in
      SC (P < 0.05). Eight PC vs. two SC patients had non-closure-related complications
      (P < 0.05). Four PC vs. zero SC patients developed necrotizing enterocolitis (P <
      0.05). Five PC vs. one SC patients had ventral hernia (P < 0.05). No patient
      died. CONCLUSION: PC resulted in higher incidence of reclosure, non-closure
      related complications, and necrotizing enterocolitis. Consequently, we recommend
      SC as the preferred treatment.

PMID- 16602847
TI  - Mean platelet and red blood cell volume measurements to estimate the severity of
      hypertension in pregnancy.

PMID- 16602848
TI  - Torsion of a pedunculated accessory hepatic lobe: differential diagnosis of
      projectile vomiting in a neonate.

PMID- 16602849
TI  - Massive fetomaternal hemorrhage following failed external cephalic version: case
      report.

PMID- 16602850
TI  - Resolution of peripheral tissue ischemia secondary to arterial vasospasm
      following treatment with a topical nitroglycerin device in two newborns: case
      reports.

PMID- 16602851
TI  - Echocardiography and N-terminal pro BNP.

PMID- 16602852
TI  - Frontal-dominant white matter lesions following congenital rubella and
      cytomegalovirus infection.

PMID- 16602928
TI  - The influence of iron status on iodine utilization and thyroid function.
AB  - Despite significant progress, deficiencies of iron and iodine remain major public
      health problems affecting > or =30% of the global population. These deficiencies
      often coexist in children. Recent studies have demonstrated that a high
      prevalence of iron deficiency among children in areas of endemic goiter may
      reduce the effectiveness of iodized salt programs. These findings argue strongly
      for improving iron status in areas of overlapping deficiency, not only to combat
      anemia but also to increase the efficacy of iodine prophylaxis. The dual
      fortification of salt with iodine and iron may prove to be an effective and
      sustainable method to accomplish these important goals.

PMID- 16602929
TI  - Salt handling and hypertension.
AB  - The kidney plays a central role in our ability to maintain an appropriate sodium
      balance, which is critical for the determination of blood pressure. The kidney's
      capacity for salt conservation may not be widely appreciated, and in general we
      consume vastly more salt than we need. Here we consider the socioeconomics of
      salt consumption, outline current knowledge of renal salt handling at the
      molecular level, describe some of the disease entities associated with abnormal
      sodium handling, give an overview of some of the animal models and their
      relevance to human disease, and examine the evidence that lowering our salt
      intake can help combat hypertension and cardiovascular disease.

PMID- 16602930
TI  - Food allergies: prevalence, molecular characterization, and treatment/prevention
      strategies.
AB  - A significant proportion of the population is either affected by or concerned
      about food allergy. Our knowledge about food allergens and how they stimulate the
      immune system has increased dramatically over the past decade. However, reasons
      for the increased prevalence of food allergy are not clear. The diagnosis of food
      allergy requires that the patient and caregivers examine all foods for the
      presence of potential allergens in order to prevent inadvertent ingestion and
      further reactions. Fortunately, many children develop tolerance to allergenic
      foods after a period of dietary elimination. Various immunotherapy approaches are
      under investigation to alleviate or prevent food-induced reactions in those who
      have persistent food allergies.

PMID- 16602931
TI  - Glucagon-like Peptide-2.
AB  - Multiple peptide hormones produced within the gastrointestinal system aid in the
      regulation of energy homeostasis and metabolism. Among these is the
      intestinotrophic peptide glucagon-like peptide-2 (GLP-2), which is released
      following food intake and plays a significant role in the adaptive regulation of
      bowel mass and mucosal integrity. The discovery of GLP-2's potent growth
      promoting and cytoprotective effects in the gastrointestinal (GI) tract
      stimulated interest in its use as a therapeutic agent for the treatment of GI
      diseases involving malabsorption, inflammation, and/or mucosal damage. Current
      research has focused on determining the physiological mechanisms contributing to
      the effects of GLP-2 and factors regulating its biological mechanisms of action.
      This chapter provides an overview of the biology of GLP-2 with a focus on the
      most recent findings on the role of this peptide hormone in the normal and
      diseased GI tract.

PMID- 16602932
TI  - Cancer-associated cachexia and underlying biological mechanisms.
AB  - Cancer metastases (spread to distant organs from the primary tumor site) signify
      systemic, progressive, and essentially incurable malignant disease. Anorexia and
      wasting develop continuously throughout the course of incurable cancer. Overall,
      in Westernized countries nearly exactly half of current cancer diagnoses end in
      cure and the other half end in death; thus, cancer-associated cachexia has a high
      prevalence. The pathophysiology of cancer-associated cachexia has two principal
      components: a failure of food intake and a systemic
      hypermetabolism/hypercatabolism syndrome. The superimposed metabolic changes
      result in a rate of depletion of physiological reserves of energy and protein
      that is greater than would be expected based on the prevailing level of food
      intake. These features indicate a need for nutritional support, metabolic
      management, and a clear appreciation of the context of life-limiting illness.

PMID- 16602946
TI  - Significance of inducible defense-related proteins in infected plants.
AB  - Inducible defense-related proteins have been described in many plant species upon
      infection with oomycetes, fungi, bacteria, or viruses, or insect attack. Several
      types of proteins are common and have been classified into 17 families of
      pathogenesis-related proteins (PRs). Others have so far been found to occur more
      specifically in some plant species. Most PRs and related proteins are induced
      through the action of the signaling compounds salicylic acid, jasmonic acid, or
      ethylene, and possess antimicrobial activities in vitro through hydrolytic
      activities on cell walls, contact toxicity, and perhaps an involvement in defense
      signaling. However, when expressed in transgenic plants, they reduce only a
      limited number of diseases, depending on the nature of the protein, plant
      species, and pathogen involved. As exemplified by the PR-1 proteins in
      Arabidopsis and rice, many homologous proteins belonging to the same family are
      regulated developmentally and may serve different functions in specific organs or
      tissues. Several defense-related proteins are induced during senescence, wounding
      or cold stress, and some possess antifreeze activity. Many defense-related
      proteins are present constitutively in floral tissues and a substantial number of
      PR-like proteins in pollen, fruits, and vegetables can provoke allergy in humans.
      The evolutionary conservation of similar defense-related proteins in monocots and
      dicots, but also their divergent occurrence in other conditions, suggest that
      these proteins serve essential functions in plant life, whether in defense or
      not.

PMID- 16602947
TI  - A retrospective of an unconventionally trained plant pathologist: plant diseases
      to molecular plant pathology.
AB  - Plant pathology evolved from its mycology-oriented origins into a science dealing
      with biochemical mechanisms of diseases, along with enhanced crop production
      through disease control. This retrospective describes first my personal
      experience from my introduction to plant pathology, to the establishment of the
      concept of accessibility as a model pertaining to genetically defined basic
      compatibility induced by pathogens. I then refer to the development of molecular
      plant pathology from physiological and biochemical plant pathology fostered by
      the growth in recombinant technology in the second half of the past century. This
      progress was best reflected by the U.S.-Japan Seminar Series held at 4-5-year
      intervals from 1966 to 2003 and documented by publications in major journals of
      our discipline. These seminars emphasized that progress in science has always
      been supported by the invention of novel techniques and that knowledge integrated
      from modern genomics and subsequent proteomics should contribute to the progress
      of basic life sciences and, more importantly, to the elaboration of rational
      measures for disease control.

PMID- 16602948
TI  - Virus-vector interactions mediating nonpersistent and semipersistent transmission
      of plant viruses.
AB  - Most plant viruses are absolutely dependent on a vector for plant-to-plant
      spread. Although a number of different types of organisms are vectors for
      different plant viruses, phloem-feeding Hemipterans are the most common and
      transmit the great majority of plant viruses. The complex and specific
      interactions between Hemipteran vectors and the viruses they transmit have been
      studied intensely, and two general strategies, the capsid and helper strategies,
      are recognized. Both strategies are found for plant viruses that are transmitted
      by aphids in a nonpersistent manner. Evidence suggests that these strategies are
      found also for viruses transmitted in a semipersistent manner. Recent
      applications of molecular and cell biology techniques have helped to elucidate
      the mechanisms underlying the vector transmission of several plant viruses. This
      review examines the fundamental contributions and recent developments in this
      area.

PMID- 16602949
TI  - Coexistence of related pathogen species on arable crops in space and time.
AB  - This review considers factors affecting the coexistence of closely related
      pathogen species on arable crops, with particular reference to data available at
      Rothamsted for Septoria tritici/Stagonospora nodorum (Mycosphaerella
      graminicola/Phaeosphaeria nodorum) (septoria leaf blotch diseases on winter
      wheat), Oculimacula yallundae/O. acuformis (eyespot disease of winter cereals),
      and Leptosphaeria maculans/L. biglobosa (phoma stem canker on winter oilseed
      rape). Factors affecting the short-term, medium-term, and long-term coexistence
      of such related pathogen species are reviewed, and their evolution from common
      ancestors considered. Small niche differences between the related pathogen
      species enable them to coexist on the same host. The niche differences result
      from small differences in their biology/epidemiology, leading to separation in
      space, time, or resource use. Changes in both natural (e.g., fluctuating
      temperature) and man-made (e.g., agronomic practices, pollution) factors
      influence the coexistence. Such factors may result in coexistence between the
      related species in some parts of the world, whereas in other parts only one
      species occurs. These principles illustrated with pathogens of arable crops are
      generic to other host-pathogen systems.

PMID- 16602950
TI  - The role of ethylene in host-pathogen interactions.
AB  - The phytohormone ethylene is a principal modulator in many aspects of plant life,
      including various mechanisms by which plants react to pathogen attack. Induced
      ethylene biosynthesis and subsequent intracellular signaling through a single
      conserved pathway have been well characterized. This leads to a cascade of
      transcription factors consisting of primary EIN3-like regulators and downstream
      ERF-like transcription factors. The latter control the expression of various
      effector genes involved in various aspects of systemic induced defense responses.
      Moreover, at this level significant cross-talk occurs with other defense response
      pathways controlled by salicylic acid and jasmonate, eventually resulting in a
      differentiated disease response.

PMID- 16602974
TI  - Molecular subtyping and the transformation of public health.

PMID- 16602976
TI  - Interpretation of pulsed-field gel electrophoresis patterns in foodborne disease
      investigations and surveillance.
AB  - Since the establishment of the well-known Tenover criteria in 1995 (Tenover et
      al., 1995), relatively few papers have been published about the interpretation of
      subtyping data generated by pulsed-field gel electrophoresis (PFGE). This paper
      describes the approach that has been used in the PulseNet network during the past
      10 years. PFGE data must always be interpreted in the proper epidemiological
      context and PFGE data can not alone prove an epidemiological connection. The
      Tenover criteria are not generally applicable to the interpretation of PFGE
      subtyping data of foodborne pathogens. The reproducibility of the method with a
      particular organism, the quality of the PFGE gel, the variability of the organism
      being subtyped, and the prevalence of the pattern in question must always be
      considered. Only isolates displaying indistinguishable patterns should be
      included in the detection of clusters of infections or the initial case
      definition in a point-source outbreak. More variability (patterns differing from
      each other in two to three band positions) may be accepted if the outbreak has
      been going on for some time or if person-person spread is a prominent feature. If
      epidemiological information is sufficiently strong, isolates with markedly
      different PFGE patterns may be included in an outbreak.

PMID- 16602975
TI  - PulseNet USA: a five-year update.
AB  - PulseNet USA is the molecular surveillance network for foodborne infections in
      the United States. Since its inception in 1996, it has been instrumental in
      detection, investigation and control of numerous outbreaks caused by Shiga toxin
      producing Escherichia coli O157:[H7] (STEC O157), Salmonella enterica, Listeria
      monocytogenes, Shigella spp., and Campylobacter. This paper describes the current
      status of the network, including the methodologies used and its future
      possibilities. The currently preferred subtyping method in the network is pulsed
      field gel electrophoresis (PFGE), a proven highly discriminatory molecular
      subtyping method. New simpler sequencebased subtyping methods are under
      development and validation to complement and eventually replace PFGE. PulseNet is
      essentially a cluster detection network, but the data in the system will now also
      be used in attribution analyses of sporadic infections. The PulseNet platform
      will also be used as a primary tool in preparedness and response to acts of food
      bioterrorism.

PMID- 16602977
TI  - Commentary: cluster evaluation, PulseNet, and public health practice.

PMID- 16602978
TI  - Building PulseNet International: an interconnected system of laboratory networks
      to facilitate timely public health recognition and response to foodborne disease
      outbreaks and emerging foodborne diseases.
AB  - PulseNet USA, the national molecular subtyping network for foodborne disease
      surveillance, began functioning in the United States in 1996 and soon established
      itself as a critical early warning system for foodborne disease outbreaks,
      particularly those in which cases may be geographically dispersed. The PulseNet
      network is now being replicated in different ways in Canada, Europe, the Asia
      Pacific region, and Latin America. These independent networks work together in
      PulseNet International allowing public health officials and laboratorians to
      share molecular epidemiologic information in real-time and enabling rapid
      recognition and investigation of multi-national foodborne disease outbreaks.
      Routine communication between the various international PulseNet networks will
      provide early warning on foodborne disease outbreaks to participating public
      health institutions and countries.

PMID- 16602979
TI  - Development and validation of a PulseNet standardized pulsed-field gel
      electrophoresis protocol for subtyping of Vibrio cholerae.
AB  - PulseNet is a network that utilizes standardized pulsed-field gel electrophoresis
      (PFGE) protocols with the purpose of conducting laboratory-based surveillance of
      foodborne pathogens. PulseNet standardized PFGE protocols are subject to rigorous
      testing during the developmental phase and careful evaluation during a validation
      process assessing its robustness and reproducibility in different laboratories.
      Here we describe the development and validation of a rapid PFGE protocol for
      subtyping Vibrio cholerae for use in PulseNet International activities. While the
      protocol was derived from the existing PulseNet protocol for Escherichia coli
      O157, various aspects of this protocol were optimized for use with V. cholerae,
      most notably a change of the primary and secondary restriction enzyme to SfiI and
      NotI, respectively, and the use of a two-block electrophoresis program. External
      validation of this protocol was undertaken through a collaboration between three
      PulseNet Asia Pacific laboratories (Public Health Laboratory Centre, Hong Kong,
      National Institute of Infectious Diseases, Japan, and International Center for
      Diarrhoeal Diseases Research-Bangladesh) and PulseNet USA. Comparison of PFGE
      patterns generated by each of the participating laboratories demonstrated that
      the protocol is robust and reproducible.

PMID- 16602980
TI  - Standardization of pulsed-field gel electrophoresis protocols for the subtyping
      of Escherichia coli O157:H7, Salmonella, and Shigella for PulseNet.
AB  - Standardized rapid pulsed-field gel electrophoresis (PFGE) protocols for the
      subtyping of Escherichia coli O157:H7, Salmonella serotypes, and Shigella species
      are described. These protocols are used by laboratories in PulseNet, a network of
      state and local health departments, and other public health laboratories that
      perform real-time PFGE subtyping of these bacterial foodborne pathogens for
      surveillance and outbreak investigations. Development and standardization of
      these protocols consisted of a thorough optimization of reagents and reaction
      conditions to ensure that the protocols yielded consistent results and high
      quality PFGE pattern data in all the PulseNet participating laboratories. These
      rapid PFGE protocols are based on the original 3-4-day standardized procedure
      developed at Centers for Disease Control and Prevention that was validated in
      1996 and 1997 by eight independent laboratories. By using these rapid
      standardized PFGE protocols, PulseNet laboratories are able to subtype foodborne
      pathogens in approximately 24 h, allowing for the early detection of foodborne
      disease case clusters and often aiding in the identification of the source
      responsible for the infections.

PMID- 16602981
TI  - Effectiveness of pulsed-field gel electrophoresis for the early detection of
      diffuse outbreaks due to Shiga toxin-producing Escherichia coli in Japan.
AB  - We applied pulsed-field gel electrophoresis (PFGE) to the investigation of
      diffuse outbreaks of illness due to Shiga toxin?producing Escherichia coli
      O157:H7 (STEC O157) in Japan and used these data to develop a database of STEC
      O157 PFGE patterns and associated clinical and microbiologic information to
      facilitate the recognition of geographic and temporal clusters of cases based on
      their PFGE profiles. This project has evolved into a subtyping network called
      PulseNet Japan that is cooperatively run by National Institute of Infectious
      Diseases (NIID) and the local Health Institutes and the Ministry of Health, Labor
      and Welfare. Although our domestic PFGE network that utilized locally developed
      PFGE protocols was effective in recognizing diffuse outbreaks of STEC O157 within
      Japan, we decided to adopt the standardized PFGE protocols from PulseNet USA and
      collaborate closely with the Centers for Disease Control and Prevention (CDC) in
      the United States to facilitate recognition of international clusters of STEC
      O157 and their investigations.

PMID- 16602982
TI  - Standardized pulsed-field gel electrophoresis of Shiga toxin-producing
      Escherichia coli: the PulseNet Europe Feasibility Study.
AB  - PulseNet USA, the American molecular subtyping network for foodborne infections,
      has since 1996 been highly successful combating infections caused by Shiga toxin
      producing Escherichia coli (STEC) O157, Salmonella, Listeria, and Shigella spp.
      The PulseNet Europe feasibility study was initiated to ascertain the interest of
      public health and veterinary reference laboratories to establish a similar
      network, and to determine if it was possible to perform standardized pulsed-field
      gel electrophoresis (PFGE) typing of Salmonella, Listeria, and STEC on a large
      scale in Europe. The results of the STEC part of that study are presented here.
      Twenty-seven veterinary and public health laboratories participated in the study.
      The participants subtyped eight E. coli strains by PFGE using the restriction
      enzyme XbaI according to the PulseNet or a similar protocol, with strict
      adherence to the electrophoretic conditions stated in the former and submitted an
      image of their gel for centralized anonymous analysis. The quality of the gels
      was first graded visually as "good," "intermediate," and "unsatisfactory." The
      number of gels graded this way was 11, 14, and 2, respectively. All "good" and
      "intermediate" gels were also analysed and compared by computerized analysis to a
      reference gel. For gels graded "good," on average 5.6, 7.4, and 8 patterns out of
      8 per gel were identified with a similarity of 100%, >95%, and >90%,
      respectively. The corresponding numbers for gels graded "intermediate" were 1.7,
      4.9, and 7.4, respectively. The problems causing the grading to be "intermediate"
      was overloaded lanes, overexposed images, not optimally focused images and
      incomplete digestion, all problems that led to misinterpretation of the number of
      restriction fragments in the gel. These problems may be corrected by simple
      adjustments to the subtyping procedure. Thus, there seems to be little need for
      training of the participants in PulseNet Europe.

PMID- 16602983
TI  - Continuous surveillance of Shiga toxin-producing Escherichia coli infections by
      pulsed-field gel electrophoresis shows that most infections are sporadic.
AB  - The purpose of this study was to evaluate the value of real-time molecular typing
      of Shiga toxin (Verocytotoxin)-producing Escherichia coli (STEC) infections in
      order to detect possible outbreaks of infections. All laboratory confirmed STEC
      infections in Denmark from 2003 to mid 2005 were routinely characterized by
      serotyping, virulence genes characterization, and subtyping by pulsed-field gel
      electrophoresis (PFGE) using the PulseNet protocol for STEC O157. The study
      included 312 STEC isolates representing 50 different O groups and 75 O:H
      serotypes, and 68% of the isolates belonged to the eight most common O-groups:
      O157 (26%), O103 (13%), O146 (8%), O26 (8%), O117 (4%), O145 (3%), O128 (3%), and
      O111 (2%). The remaining O-groups constituted less than 2% each, and 8.1% of the
      isolates were O-rough. The eae gene was found in 60% of all isolates, and
      detection of the two main Shiga toxin genes showed that 40% had stx1 only, 31%
      had stx2 only, and 29% had both stx1 and stx2. A high diversity was seen within
      all O groups, and for most of the rare O groups, the number of PFGE profiles
      equaled the number of isolates. However, one outbreak of E. coli O157 was
      detected by the routine PFGE typing. The value of "real-time' PFGE typing of the
      infrequent serotypes is limited if the full scheme for O-grouping or O:H
      serotyping is used routinely for all STEC isolates. Possible outbreaks can then
      be detected by the increased number of isolates within a particular serotype.
      PFGE typing would then be valuable in subsequent steps of the outbreak
      investigation. However, routine PFGE typing of the three to five most common O
      groups will enable early recognition of possible outbreaks.

PMID- 16602984
TI  - Characterization and epidemiologic subtyping of Shiga toxin-producing Escherichia
      coli strains isolated from hemolytic uremic syndrome and diarrhea cases in
      Argentina.
AB  - Argentina has a high incidence of hemolytic uremic syndrome (HUS); 12.2 cases per
      100,000 children younger than 5 years old were reported in 2002. Shiga toxin
      (Stx)-producing Escherichia coli (STEC) is the primary etiologic agent of HUS,
      and STEC O157 is the predominant serogroup isolated. The main objective of the
      present work was to establish the phenotypic and genotypic characteristics of the
      STEC strains in general isolated from Argentine children during a prospective
      study and the clonal relatedness of STEC O157:H7 strains using subtyping
      techniques. One hundred and three STEC strains isolated from 99 children were
      included. The phenotypic and genotypic features were established, and a
      polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) was
      performed to determine stx2 variants. The clonal relatedness of E. coli O157
      isolates was established by phage typing and pulsed-field gel electrophoresis
      (PFGE). The 103 STEC strains belonged to 18 different serotypes, and 59% were of
      serotype O157:H7. Stx2 was identified in 90.3%, and stx1 in 9.7%. Among the 61
      STEC O157 strains, 93.4% harbored the stx2/stx2vh-a genes; PT4 (39.3%) and PT2
      (29.5%) were the predominant phage types. Using PFGE with the enzyme XbaI, a
      total of 41 patterns with at least 80% similarity were identified, and seven
      clusters with identical profiles were established. Some of the clusters were
      further split by PFGE using BlnI as the second enzyme. Isolates with
      indistinguishable PFGE patterns were with one exception also indistinguishable by
      phage typing and stx genotyping. These findings confirmed that some isolates were
      genetically related. However, no epidemiological linkages were identified. STEC
      strains with different genotypes and belonging to diverse serotypes were isolated
      in Argentina. Some STEC O157 strains could not be distinguished by applying
      subtyping techniques such as PFGE and phage typing.

PMID- 16602985
TI  - Genomic diversity within phage types of Salmonella enterica ssp. enterica
      serotypes Enteritidis and Typhimurium.
AB  - The diversity among 1354 strains of Salmonella enterica subsp. enterica, serotype
      Enteritidis (n = 847) and Typhimurium (n = 507) isolated in Finland in 1991-2002
      (n = 608) and in 2003 (n = 746) were studied. The former strains were studied
      retrospectively by phage typing and pulsed-field gel electrophoresis (PFGE)
      harmonized in the European Salm-gene project. The latter strains were studied
      prospectively, and the results correlated to their antimicrobial susceptibility
      and association with travel to popular tourist destinations. During both periods,
      S. Enteritidis phage types (PTs) PT1 and PT4, and S. Typhimurium definite types
      (DTs) DT1 and DT104 were the major phenotypes. SENTXB.0001 was the dominating
      single PFGE type among S. Enteritidis strains (40% in 1991-2002; 57% in 2003),
      and accounted correspondingly for 23% and 63% of the PT1 strains, and 81% and 88%
      of the PT4 strains. No PFGE types dominated among the S. Typhimurium strains but
      a correlation was found between certain phage and PFGE types: among DT1 strains,
      STYMXB.0098 accounted for 66% (1991-2002) and 98% (2003) and among the DT104
      strains STYMXB.0001 accounted for 84% and 97% in the two time periods,
      respectively. Of the S. Enteritidis strains isolated in 2003, 91% were associated
      with travel, most commonly to Spain, Greece, and Bulgaria. SENTXB.0001 was the
      major Salmonella PFGE type in these countries. In contrast, most (55%) S.
      Typhimurium strains were of domestic origin. While only 1.3% of the S.
      Enteritidis strains were multiresistant and 24% were resistant to nalidixic acid
      only, 30% of the S. Typhimurium strains were multiresistant. Among the
      multiresistant S. Typhimurium strains, R-type ACSSuT and PFGE type STYMXB.0001 of
      the DT104 complex dominated.

PMID- 16602986
TI  - Antimicrobial resistance and genetic relatedness among Salmonella from retail
      foods of animal origin: NARMS retail meat surveillance.
AB  - Salmonella isolates were recovered from a monthly sampling of chicken breasts,
      ground turkey, ground beef, and pork chops purchased from selected grocery stores
      in six participating FoodNet sites (Connecticut, Georgia, Maryland, Minnesota,
      Oregon, and Tennessee) in 2002 and an additional two sites in 2003 (California
      and New York). In 2002 and 2003, a total of 6,046 retail meats were examined,
      including 1,513 chicken breasts, 1,499 ground turkey samples, 1,522 ground beef
      samples, and 1,502 pork chops. Retail meat samples tested increased to 3,533 in
      2003 as compared to 2,513 in 2002. Overall, six percent of 6,046 retail meat
      samples (n = 365) were contaminated with Salmonella, the bulk recovered from
      either ground turkey (52%) or chicken breast (39%). Salmonella isolates were
      serotyped and susceptibility tested using a panel of 16 antimicrobial agents. S.
      Heidelberg was the predominant serotype identified (23%), followed by S.
      Saintpaul (12%), S. Typhimurium (11%), and S. Kentucky (10%). Overall, resistance
      was most often observed to tetracycline (40%), streptomycin (37%), ampicillin
      (26%), and sulfamethoxazole (25%). Twelve percent of isolates were resistant to
      cefoxitin and ceftiofur, though only one isolate was resistant to ceftriaxone.
      All isolates were susceptible to amikacin and ciprofloxacin; however, 3% of
      isolates were resistant to nalidixic acid and were almost exclusive to ground
      turkey samples (n = 11/12). All Salmonella isolates were analyzed for genetic
      relatedness using pulsed-field gel electrophoresis (PFGE) patterns generated by
      digestion with Xba1 or Xba1 plus Bln1. PFGE fingerprinting profiles showed that
      Salmonella, in general, were genetically diverse with a total of 175 Xba1 PFGE
      profiles generated from the 365 isolates. PFGE profiles showed good correlation
      with serotypes and in some instances, antimicrobial resistance profiles. Results
      demonstrated a varied spectrum of antimicrobial resistance and PFGE patterns,
      including several multidrug resistant clonal groups among Salmonella isolates,
      and signify the importance of sustained surveillance of foodborne pathogens in
      retail meats.

PMID- 16602987
TI  - Second generation subtyping: a proposed PulseNet protocol for multiple-locus
      variable-number tandem repeat analysis of Shiga toxin-producing Escherichia coli
      O157 (STEC O157).
AB  - Most bacterial genomes contain tandem duplications of short DNA sequences, termed
      "variable-number tandem repeats" (VNTR). A subtyping method targeting these
      repeats, multiple-locus VNTR analysis (MLVA), has emerged as a powerful tool for
      characterization of clonal organisms such as Shiga toxin-producing Escherichia
      coli O157 (STEC O157). We modified and optimized a recently published MLVA scheme
      targeting 29 polymorphic VNTR regions of STEC O157 to render it suitable for
      routine use by public health laboratories that participate in PulseNet, the
      national and international molecular subtyping network for foodborne disease
      surveillance. Nine VNTR loci were included in the final protocol. They were
      amplified in three PCR reactions, after which the PCR products were sized using
      capillary electrophoresis. Two hundred geographically diverse, sporadic and
      outbreak- related STEC O157 isolates were characterized by MLVA and the results
      were compared with data obtained by pulsed-field gel electrophoresis (PFGE) using
      XbaI macrorestriction of genomic DNA. A total of 139 unique XbaI PFGE patterns
      and 162 MLVA types were identified. A subset of 100 isolates characterized by
      both XbaI and BlnI macrorestriction had 62 unique PFGE and MLVA types. Although
      the clustering of isolates by the two subtyping systems was generally in
      agreement, some discrepancies were observed. Importantly, MLVA was able to
      discriminate among some epidemiologically unrelated isolates which were
      indistinguishable by PFGE. However, among strains from three of the eight
      outbreaks included in the study, two single locus MLVA variants and one double
      locus variant were detected among epidemiologically implicated isolates that were
      indistinguishable by PFGE. Conversely, in three other outbreaks, isolates that
      were indistinguishable by MLVA displayed multiple PFGE types. An additional more
      extensive multi-laboratory validation of the MLVA protocol is in progress in
      order to address critical issues such as establishing epidemiologically relevant
      interpretation guidelines for the MLVA data.

PMID- 16602988
TI  - Canadian listeriosis reference service.
AB  - Listeria monocytogenes, a psychrotrophic organism capable of growing at
      refrigeration temperatures, is of major concern in extended shelf life,
      refrigerated foods. Considering that as much as 80-90% of human listeriosis cases
      are linked to the ingestion of contaminated food, human cases are predominantly
      seen in high-risk individuals, including organ-transplant recipients, patients
      with AIDS and HIV-infected individuals, pregnant women, cancer patients, and the
      elderly. In 2001, the Canadian Listeriosis Reference Service (LRS) was created by
      the Bureau of Microbial Hazards (Health Canada) and the National Microbiology
      Laboratory (now part of the Public Health Agency of Canada). Major goals of the
      LRS include investigation of listeriosis cases and maintenance of a national
      collection of isolates. The LRS intends to create a comprehensive molecular
      epidemiological database of all isolates in Canada for use as a resource for
      outbreak investigations, research and other microbiological investigations. The
      PFGE profiles are being established and stored for clinical, food, environmental,
      and possibly animal strains of L. monocytogenes. The LRS pursues research
      activities for investigation and implementation of other molecular methods for
      characterizing L. monocytogenes isolates. Ribotyping, Multi-locus Sequence Typing
      (MLST), Variable Number of Tandem Repeats (VNTR), Multi-locus virulence sequence
      typing (MLVA), microarray- based technologies and sequence-based typing schemes,
      are being investigated on selected diversity sets. The LRS has also used PFGE
      typing for outbreak investigations. The molecular epidemiological data, timely
      coordination and exchange of information should help to reduce the incidence of
      listeriosis in Canada. In Canada, listeriosis is not a national notifiable
      disease, except for the province of Quebec, where it has been since 1999. The
      LRS, Canadian Public Health Laboratory Network, and federal epidemiologists are
      currently working on making human listeriosis notifiable throughout Canada.

PMID- 16602989
TI  - A comparison of Listeria monocytogenes serovar 4b isolates of clinical and food
      origin in Austria by automated ribotyping and pulsed-field gel electrophoresis.
AB  - In this study, two typing methods, automated ribotyping and pulsed-field gel
      electrophoresis (PFGE), were evaluated for the subtyping of Listeria
      monocytogenes serotype 4b. The strains originated from patients and food samples
      collected in Austria during 2001-2005 and from Europe and North America in the
      World Health Organization collaborative study on the subtyping of this species.
      The largest group of Austrian clinical isolates was of the same PFGE subtype as
      those isolated from foodborne outbreaks in Switzerland and in the United States.
      Another subtype of clinical isolates from Austria was indistinguishable to that
      obtained from isolates responsible for a foodborne outbreak in the United States
      in 1985. Although the discriminatory power of PFGE was higher than that of
      automated ribotyping, some PFGE types were differentiated by ribotyping. Thus,
      combining data obtained by both automated ribotyping and PFGE increases the
      strain discrimination. Still, many of the Austrian strains remain
      indistinguishable from strains of foodborne outbreaks in other countries although
      there is no known epidemiological relation. This complies to previous studies
      which show the highly clonal nature of L. monocytogenes 4b strains which are
      responsible for both large outbreaks and sporadic cases.

PMID- 16602990
TI  - Molecular subtyping of Salmonella enterica serovar Typhi isolates from Colombia
      and Argentina.
AB  - Salmonella Typhi is the etiological agent of typhoid fever with 16 million annual
      cases estimated worldwide. In Colombia and Argentina it is a notifiable disease
      but many cases have only a clinical diagnosis. Molecular subtyping of S. Typhi is
      necessary to complement epidemiologic analysis of typhoid fever. The aims of this
      study were to determine the genetic relationships between the strains circulating
      in both countries and to evaluate possible variations in the distribution of 12
      virulence genes. A total of 136 isolates were analyzed by pulsed-field gel
      electrophoresis (PFGE) with XbaI following PulseNet protocols and analysis
      guidelines. Eighty-three different PFGE patterns were identified, showing high
      diversity among the strains from both countries. Three outbreaks, two in Colombia
      and one in Argentina, were caused by strains of different PFGE types. In
      Colombia, two PFGE patterns were found predominantly, which included 36.6% of the
      isolates from that country. No association was found between the PFGE patterns
      and the year or place of isolation of the strains, the age of the patients or
      type of sample. However, several clusters were detected, which included isolates
      recovered predominantly either from Colombia or Argentina. Most of the strains
      (97%) exhibited a single virulence profile, suggesting that the pathogenicity
      markers analyzed are of limited value for strain discrimination and do not
      correlate with the origin of the isolates (intestinal vs. extra-intestinal).
      Since the creation of PulseNet Latin America, this was the first international
      study conducted in South America. The PFGE types identified were incorporated
      into the Regional S. Typhi PulseNet Database and are now available for comparison
      with those of strains isolated in other regions. This information will be used
      for active surveillance, future studies, and outbreak investigations.

PMID- 16602991
TI  - Finding common ground in acid-base.

PMID- 16602992
TI  - "Shh! I think it's the patient".

PMID- 16602993
TI  - Australian multi-centre clinical trials: design and sample size.

PMID- 16602994
TI  - Hypertonic saline for initial resuscitation? I'd like to see that!

PMID- 16602995
TI  - The Effect of Preoperative Aspirin and/or Heparin Therapy on Coagulation and
      Postoperative Blood Loss after Coronary Artery Bypass Surgery.
AB  - OBJECTIVE: To assess the effects of preoperative aspirin and/or intravenous
      heparin therapy on perioperative coagulation tests and postoperative blood loss
      for 24-hour after coronary artery bypass surgery. METHODS: Multiple conventional
      coagulation tests, activated clotting time, thrombelastograph, skin bleeding time
      and platelet aggregation were performed before induction of anaesthesia,
      following protamine administration and after skin closure in 45 patients.
      RESULTS: There was no significant difference in either coagulation tests or
      postoperative blood loss (median of 860 mL with a range of 275 to 2800 mL, versus
      833 ml with a range of 500-1380 mL) between the aspirin and no-aspirin patients.
      Preoperative heparin therapy affected most coagulation tests (e.g. international
      normalised ratio, activated partial thromboplastin time, thrombin clotting time,
      prothrombin time, activated clotting time and coagulation time of
      thrombelastography) before anaesthesia. The effects disappeared following
      protamine administration and after skin closure. Post operative blood loss was
      not significantly increased for the heparin group compared with the no-heparin
      group (median of 850 mL with a range of 700-1400 mL, versus 856 mL with a range
      of 275-2800 mL, respectively). Similar results were seen in patients receiving
      preoperative co-administration of aspirin and heparin compared with patients
      receiving aspirin alone. There was no suppression of platelet activity in
      patients receiving preoperative heparin or co-administration of aspirin and
      heparin. However, such suppression was found in patients receiving aspirin only.
      CONCLUSION: This study suggests that preoperative aspirin ingestion and
      intravenous heparin therapy should be administered as indicated and that concerns
      about the risk of postoperative bleeding should not lead to modification or
      cessation of such therapy.

PMID- 16602996
TI  - Continuous Intra-arterial Blood Gas Monitoring.
AB  - OBJECTIVE: To review the technology and the role of continuous intra-arterial
      blood gas monitoring in critical illness. DATA SOURCES: Articles and published
      peer review abstracts on continuous intra-arterial blood gas monitoring. SUMMARY
      OF REVIEW: The history of intermittent and continuous blood gas analysis and the
      development of technology of continuous blood gas monitoring are reviewed. A
      summary of the various clinical trials on the evaluation of continuous blood gas
      monitoring systems, and the various factors which might affect the performance
      characteristics in the clinical setting is also presented. The potential role and
      future applications of this technology in critical illness are described.
      CONCLUSIONS: Over the last 10 years, a number of continuous intra-arterial blood
      gas monitoring systems have been developed. Only a few have reached commercial
      availability. While the performance characteristics of these systems are
      comparable, the levels of accuracy of these systems obtained in vitro are not
      consistently obtained in clinical trials. Arterial blood flow, wrist movement,
      wall effect and variability of blood gas analysers are some of the factors which
      determine the accuracy and reproducibility of these systems. Evidence to support
      the clinical usefulness of these monitors exists only in the form of case
      studies. Controlled studies demonstrating an improvement in outcome with the use
      of these monitors are lacking.

PMID- 16602997
TI  - Intravenous fluid administration and controversies in Acid-base.
AB  - OBJECTIVE: To present an overview of acidosis following intravenous fluid
      infusion and to highlight the current controversy in acid-base physiology. DATA
      SOURCES: Articles and reviews from peer reviewed journals and books on acid-base
      physiology and post infusion acidosis. SUMMARY OF REVIEW: Infusion of intravenous
      fluids can produce an acidosis particularly in the setting of large volume
      infusion. The explanation of this phenomenon has centred around dilution of
      plasma bicarbonate. An alternative explanation can be found in the work of Peter
      Stewart, which highlights the use of strong ion difference in assessing metabolic
      acidosis. The Stewart approach differs from the traditional Henderson-Hasselbalch
      approach to acid-base. Further study is required to determine which approach is
      correct. Solutions containing base anions such as lactate may attenuate such an
      infusion acidosis. Animal and clinical studies using Hartmann's solution and
      Plasmalyte 148 support this idea. CONCLUSIONS: There is controversy regarding
      mechanisms in acid-base physiology. The clinical significance of post infusion
      acidosis is unclear, however use of Hartmann's solution may minimize the
      acidosis.

PMID- 16602998
TI  - Hypertonic saline resuscitation for head injured patients.
AB  - OBJECTIVE: To discuss the reasons why 250 ml 7.5% hypertonic saline was chosen as
      a pre-hospital resuscitation fluid for head injured patients in a multicentred,
      prospective, randomised controlled trial investigating its long term effects on
      central nervous system outcome. DATA SOURCES: Recent published peer-review
      articles on the incidence and mechanisms of traumatic head injury and clinical
      use of hypertonic saline in pre-hospital resuscitation of trauma. SUMMARY OF
      REVIEW: Head injury is commonly associated with major trauma and if hypotension
      also exists the morbidity and mortality due to cerebral injury are high.
      Hypertonic saline has been used in clinical practice to treat cerebral oedema and
      resuscitate burns patients following experimental evidence that it reduces tissue
      oedema, improves blood flow to damaged organs and may reduce the incidence of
      multiple organ dysfunction, when compared with resuscitation using isotonic
      solutions. In pre-hospital trauma patients, initial resuscitation using
      hypertonic saline rather than conventional isotonic solutions has the potential
      advantage of requiring a small volume of fluid that is easily stored and
      administered, and may improve cerebral circulation and reduce the long term
      neurological effects that are determined by pre-hospital hypovolaemia and
      hypotension. To answer the question whether hypertonic saline will improve the
      outcome in trauma patients with hypotension and head injury, a multicentred,
      randomised controlled trial comparing 250 ml of 7.5% hypertonic saline (320 mmol)
      with 250 ml of Hartmann's solution (32 mmol) in pre-hospital resuscitation of
      trauma patients with a Glasgow coma score < 9 and systolic blood pressure < 100
      mmHg, began in 1998 and is anticipated to be completed by 2001. CONCLUSIONS: Pre
      hospital resuscitation of head injured and hypotensive trauma patients using
      hypertonic saline, has the potential to reduce long term cerebral injury and
      reduce social and financial costs to the community.

PMID- 16602999
TI  - Intravenous magnesium.
AB  - OBJECTIVE: To review the function and use of intravenous magnesium in magnesium
      depleted and non-magnesium depleted patients. DATA SOURCES: A review of studies
      reported from 1966 to 1998 and identified through a MEDLINE search of the English
      language literature on the use of intravenous magnesium. SUMMARY OF REVIEW:
      Magnesium is a metalo-coenzyme that participates in numerous enzymatic reactions
      including all reactions that involve the formation and utilization of ATP. The
      cardiovascular, neurological and metabolic disorders caused by magnesium
      deficiency are associated with an increase in morbidity and mortality and can be
      rapidly corrected by magnesium therapy. There is also evidence that intravenous
      magnesium alters ion channels, NMDA receptors, and calcium metabolism, causing
      effects that are beneficial in a range of cardiovascular, respiratory and
      metabolic disorders, in the absence of magnesium deficiency. In these disorders
      intravenous magnesium sulphate is usually administered as an initial bolus
      varying between 8 - 16 mmol over 5 min, followed by an infusion of 2 - 4 mmol/h,
      to keep the plasma magnesium between 1.5 - 3 mmol/L. CONCLUSIONS: Magnesium is
      required in patients who are magnesium depleted and is also of benefit in non
      magnesium depleted patients with pre-eclampsia. It may also be of benefit in non
      magnesium depleted patients with acute coronary syndromes, arrhythmias, acute
      asthma, stroke, seizures and spinal cord injury.

PMID- 16603000
TI  - Clinical information systems in intensive care.
AB  - OBJECTIVE: To review the requirements and functions of clinical information
      systems for the critical care environment. DATA SOURCES: Peer reviewed studies
      and articles reported from 1990-1998, identified through MEDLINE search and
      subsequent article references. SUMMARY OF REVIEW: Clinical information systems
      (CIS) utilise information technologies to improve and add value to information
      management, and critical care areas have provided clinical leadership in their
      development and implementation. Expectations for these systems are high, yet
      certain basic requirements must be fulfilled. Bedside charting functions of CIS
      are highly developed and successful. Clinical record keeping has been more
      challenging, particularly the requirement for electronic storage of a medico
      legal record. Decision support ranges in its extent and requires further
      development. Successful integration with other hospital systems is highly
      desirable but may be made more difficult by the lack of rigorous technical
      standards in healthcare computing. The CIS clinical database is fundamental to
      the quality improvement, research and business reporting functions. The huge
      amount of data, the lack of common minimal and extensive data sets, and the
      technical challenges of software development, all combine to make this a resource
      expensive venture requiring on site customisation. Purchasing and implementing a
      CIS is costly in human and material resources. CONCLUSION: A high performance CIS
      is not yet available as an 'off the shelf' product. Close collaboration between
      the industry and clinicians is important for successful implementation. Clinical
      awareness of these issues will encourage product development and suitable
      purchasing strategies.

PMID- 16603001
TI  - Cerebral salt wasting syndrome: a case report.
AB  - A case of hyponatraemia associated with subarachnoid haemorrhage is presented.
      The provisional diagnosis of an inappropriate antidiuresis was made and treatment
      with fluid restriction was instituted. However the patient continued to
      deteriorate as the diuresis continued and the hyponatraemia worsened, resulting
      in hypovolaema. The salt wasting syndrome was subsequently diagnosed and saline
      and fludrocortisone (0.2 mg/day) was initiated, reducing the renal salt loss,
      increasing the plasma sodium and improving the neurological status of the
      patient. Cerebral salt wasting syndrome is an important and under-recognised
      cause of hyponatraemia in neurosurgical patients, particularly in patients with
      subarachnoid hemorrhage. It is essential to differentiate it from the syndrome of
      inappropriate antidiuretic hormone secretion to avoid complications of
      hypovolaemia and reduced cerebral perfusion as illustrated by this case. Brain
      natriuretic peptide may be responsible for this syndrome although this requires
      further investigation.

PMID- 16603002
TI  - Proximal small bowel infarction associated with portal venous gas.
AB  - Clostridium perfiringens may cause myonecrosis (i.e. gas gangrene), acute food
      poisoning or necrotic enteritis (e.g. enteritis necroticans or Pig Bel). We
      describe a case of enteritis necroticans in a 33 year old man with acute myeloid
      leukaemia. He presented with an acute abdomen, diarrhoea and pancytopaenia and
      extensive accumulation of gas in the intrahepatic and extrahepatic portal veins.
      Despite urgent resuscitation he died shortly after arrival in the Intensive Care
      Unit. Treatment of enteritis necroticans requires urgent surgery to remove dead
      bowel and in adults intravenous penicillin (1g 2-hourly) and metronidazole (500
      mg 8-hourly) or clindamycin (600 mg 6-hourly). While antibiotics may also reduce
      toxin formation, beta toxoid has not been found to be of benefit in established
      disease.

PMID- 16603003
TI  - Non.invasive ventilation for adult acute respiratory failure. Part I.
AB  - OBJECTIVE: To detail the history, modes, physiological effects, and circuit
      geometry of non-invasive ventilation. DATA SOURCES: A review of articles
      published in peer-reviewed journals from 1966 to 1998 and identified through a
      MEDLINE search on non-invasive ventilation. SUMMARY OF REVIEW: Non-invasive
      ventilation (NIV) has been used for many years as an adjunct to standard therapy
      in patients with acute and chronic respiratory disorders. The newer modes of NIV
      which include continuous positive airway pressure (CPAP), pressure support
      ventilation (PSV), BiPAP (bi-level positive airway pressure) and controlled and
      assisted modes of intermittent non-invasive positive pressure ventilation (NIPPV)
      have additional advantages and are often used routinely in many respiratory
      diseases. These modes of ventilatory support have been found to improve arterial
      oxygenation, ventilation, work of breathing, and cardiac function, in patients
      with respiratory failure, although in normal subjects, respiration is often
      impaired.. CONCLUSIONS: Non-invasive ventilation using the modes of CPAP, PSV,
      BiPAP and NIPPV should be considered in patients with respiratory failure who are
      unresponsive to conventional therapy, before considering invasive mechanical
      ventilation.

PMID- 16603004
TI  - Non.Invasive Ventilation for Adult Acute Respiratory Failure. Part II.
AB  - OBJECTIVE: To discuss the clinical indications and complications of non-invasive
      ventilation. DATA SOURCES: A review of articles published in peer-reviewed
      journals from 1966 to 1998 and identified through a MEDLINE search on non
      invasive ventilation. SUMMARY OF REVIEW: Non-invasive ventilation (NIV) has been
      used in patients with respiratory failure caused by cardiogenic pulmonary oedema,
      acute respiratory distress syndrome, acute asthma and chronic obstructive
      pulmonary disease. However, in patients with acute respiratory failure, it
      appears that acute cardiogenic pulmonary oedema and acute respiratory failure
      associated with Pneumocystis carinii pneumonia are the only disorders in which
      significant benefits have been associated with the use of the NIV mode of CPAP.
      The potential clinical benefit of CPAP in acute asthma and blunt chest trauma
      remains unclear. Pressure support ventilation is beneficial in patients with
      hypercapnic acute respiratory failure (ARF) secondary to respiratory muscle
      insufficiency, high inspiratory work loads, or reduced alveolar ventilation. It
      appears also to be associated with an improved outcome in COPD patients with
      hypercapnic ARF. CONCLUSIONS: Non-invasive ventilation using the modes of CPAP,
      PSV, BiPAP and NIPPV should be considered in patients with respiratory disorders
      who remain in acute respiratory failure despite conventional therapy, before
      considering invasive mechanical ventilation.

PMID- 16603005
TI  - Strong ion difference: a new paradigm or new clothes for the Acid-base emperor.
AB  - OBJECTIVE: To review and compare the 'metabolic' component of an acid-base
      abnormality by assessing the arterial blood bicarbonate and the 'strong ion
      difference'. DATA SOURCES: A review of published peer-review articles and studies
      reported from 1983 to 1999 and identified through a MEDLINE search on 'strong ion
      difference'. SUMMARY OF REVIEW: The Henderson-Hasselbalch equation describes the
      simple relationship between the arterial pH, PaCO(2) and bicarbonate
      concentration (HCO(3)(-)), and has been used by clinicians to classify acid-base
      abnormalities as either respiratory or a non-respiratory (i.e. metabolic).
      However, as the HCO(3)(-) concentration cannot be measured directly and as it can
      also be altered by an alteration in the PaCO(2), derived values such as the
      standard bicarbonate, buffer base, base excess and standard base excess have been
      proposed to assess the true 'metabolic' acid-base component. Recently, an
      analysis of acid-base has been reported based on the Law of electroneutrality in
      aqueous solutions, in which it is proposed that the independent variables of
      'strong ions' (e.g. sodium, potassium, calcium, magnesium, chloride and organic
      anions), CO(2) and non volatile weak acids (i.e. A(TOT)) alter the dependent
      variables of pH and HCO(3)(-). The concept of 'strong ion difference' (SID) is
      used to help explain 'metabolic' acid base abnormalities, particularly those
      associated with saline infusions. The relationship between the HCO(3)(-) ion and
      the SID can be represented as HCO(3)(-) = (SID - A(-)) and the Henderson
      Hasselbalch equation can be written as pH infinity (SID - A(.))/PaCO(2) although,
      the body regulates pH by regulating the PaCO(2) and HCO(3)(-), rather than by
      regulating the SID or A(TOT). CONCLUSIONS: In man the renal and respiratory
      systems regulate acid-base homeostasis by modifying the bicarbonate buffer pair
      (i.e. PCO(2) and HCO(3)(-)), with all other body buffer systems adjusting to
      alterations in this pair. To maintain electrical neutrality there is a change in
      cation concentration commensurate with the change in bicarbonate concentration.

PMID- 16603006
TI  - The college - How, not whether?

PMID- 16603007
TI  - "Am I going to wake up tomorrow, Sally?".

PMID- 16603008
TI  - Renal protection and salvage: precise answers require precise questions.

PMID- 16603009
TI  - Regional care of critically ill children.

PMID- 16603010
TI  - Echocardiography and the intensive care unit.

PMID- 16603011
TI  - Intravascular volume control - in concept and in clinical practice.

PMID- 16603012
TI  - Paediatric admissions to the general intensive care unit at palmerston north
      hospital.
AB  - OBJECTIVES: To report Palmerston North Hospital's (PNH) recent experiences with
      paediatric admissions to the general Intensive Care Unit (ICU), and to identify
      any aspects relevant to regionalisation of paediatric intensive care. METHODS:
      Retrospective review of the ICU database and admission register to enable
      clinical and demographic profiling of all paediatric (aged < 15 years) admissions
      to PNH ICU from 1996 to 1998. Observed and predicted mortalities were compared
      using the Paediatric Index of Mortality (PIM). RESULTS: Seventy-five paediatric
      patients had 76 admissions, comprising 7.4% of ICU admissions during the study
      period. Forty-eight (64%) were male, and 59 (79%) of the patients received
      mechanical ventilatory support. The median ICU stay was 21.5 hours (range 0.1 to
      568 hours). There were 3 deaths in the ICU, and one following ICU discharge but
      prior to hospital discharge, compared with 6.37 predicted deaths. The median PIM
      score overall was 5.3% predicted probability of death (range 0.8 - 61.4%), with 6
      patients (7.9%) having a PIM score of greater than 30%. Fifteen patients (20%)
      were transferred to tertiary services. CONCLUSIONS: If the PNH experience
      reflects that of other similar institutions, then non-tertiary ICUs admit small
      numbers of critically ill paediatric patients who tend to be of low to moderate
      severity, but who cover the full spectrum of severity. Most cases can be well
      managed locally, but appropriate referral and transfer is an important component
      in the delivery of a rational and integrated paediatric intensive care service.

PMID- 16603013
TI  - Hypokalaemia.
AB  - OBJECTIVE: To review the metabolism and function of potassium and causes and
      management of hypokalaemia. DATA SOURCES: A review of studies reported from 1966
      to 1998 and identified through a MEDLINE search of the English-language
      literature of hypokalaemia. SUMMARY OF REVIEW: Potassium is predominantly an
      intracellular ion that contributes to approximately 50% of the intracellular
      fluid osmolality and is largely responsible for the resting membrane potential.
      The latter accounts for its influence on the excitability of muscle and nervous
      tissue. Hypokalaemia is defined as a serum potassium of less than 3.5 mmol/L or
      plasma potassium less than 3.0 mmol/L and may be asymptomatic. Clinical features
      associated with hypokalaemia include abnormalities of cardiovascular,
      neurological and metabolic function and may be treated with oral potassium salts,
      although tachycardia and muscle weakness are the two life threatening disorders
      which may require rapid intravenous correction. The potassium salts of chloride,
      phosphate and acetate are often used, although the choice is often guided by the
      presence of an associated hypochloraemic alkalosis, non-anion gap acidosis or
      hypophosphataemia, indicating treatment with potassium chloride, potassium
      acetate, or potassium phosphate, respectively. The infusion rates of intravenous
      therapy depends upon the salt used. Potassium chloride is usually infused at a
      rate up to 40 mmol/h, whereas potassium acetate and potassium monohydrogen or
      dihydrogen phosphate are usually infused up to 5 mmol/h and 2 mmol/h
      respectively. CONCLUSIONS: Hypokalaemia can be asymptomatic or it may cause
      cardiovascular, neurological or skeletal muscle dysfunction. If intravenous
      potassium therapy is required, then correction with potassium chloride, acetate,
      or phosphate salts are usually guided by the presence of a metabolic acidosis,
      alkalosis or hypophosphataemia.

PMID- 16603014
TI  - Digoxin in the critically ill patient.
AB  - OBJECTIVE: To review the pharmacodynamic and pharmacokinetic properties of
      digoxin in health and disease and the potential use and toxic effects of digoxin
      in the critically ill patient. DATA SOURCES: A review of studies reported from
      1966 to 1998 and identified through a MEDLINE search of the literature on digoxin
      and the use of digoxin in critical illness. SUMMARY OF REVIEW: Digoxin inhibits
      the sarcolemmal NaK-ATPase in many tissues with the effects on myocardial
      contractile and conducting tissue, neural tissue and smooth muscle providing the
      major physiological effects in health and disease. Currently the major
      indications for its clinical use include systolic heart failure, where, in
      addition to angiotensin conversion enzyme inhibitors and diuretics, it reduces
      the incidence of pulmonary oedema, and in the management of patients with
      supraventricular tachycardia, where it reduces the ventricular rate. In the
      critically ill patient, digoxin is used infrequently as there are other agents
      that have a superior inotropic effect, a greater ability to control and reverse
      supraventricular tachyarrhythmias, have a larger therapeutic window and are
      easier to regulate. As the myocardial depression associated with septic shock is
      manifest by ventricular dilation and reduction in ejection fraction, it would
      seem that digoxin may be of some therapeutic benefit in this disorder,
      particularly as early experimental and clinical studies have reported an
      improvement in the myocardial dysfunction associated with sepsis with the use of
      intravenous digoxin (750 - 1000 mug/70 kg). However, large prospective randomised
      controlled trials are lacking. CONCLUSIONS: Digoxin is a therapeutic agent with
      unique effects. It should be considered in all patients with systolic heart
      failure, supraventricular tachycardia, and, in association with other treatment,
      as a single dose of 750 -1000 mug/70 kg in patients not treated previously with
      digoxin who have septic shock. It should be avoided in patients with critical
      coronary artery disease and ischaemic or hypertrophic diastolic failure.

PMID- 16603015
TI  - Renal protective agents: a review.
AB  - OBJECTIVE: To review the role of drugs with potential benefit to renal function
      in critically ill patients. DATA SOURCES: A review of articles published in peer
      review journals from 1966 to 1998 and identified through a MEDLINE search on
      kidney failure. SUMMARY OF REVIEW: Acute renal failure in critically ill patients
      is characterised by ischaemic injury to the tubule and is potentially
      preventable. Many agents have been shown to benefit renal function in animal
      models of acute renal failure, but supporting human data are lacking. There is
      evidence to support the defence of extracellular volume (with volume loading) and
      renal perfusion pressure (with pressor agents) but there are no controlled
      trials. While there are limited data to support the use of mannitol and calcium
      channel blockers in renal transplantation there are no studies that have
      confirmed their benefit in critically ill patients. Controlled trials of
      frusemide, dopamine and mannitol do not support their routine use. All other
      agents have been inadequately studied. CONCLUSIONS: The common factor in renal
      dysfunction and acute renal failure is tubular ischaemia. Prevention of this
      final common pathway is the chief goal of renal protection in critically ill
      patients. Despite the plethora of potentially beneficial drugs, volume loading
      and defence of renal perfusion pressure (and renal blood flow) with pressor
      agents appear to be the only reliable means of renal protection.

PMID- 16603016
TI  - Fat embolism.
AB  - OBJECTIVE: To review the pathophysiology and management of patients with clinical
      manifestations of fat embolism. DATA SOURCES: A review of studies reported from
      1976 to 1998 and identified through a MEDLINE search of the literature on fat
      embolism and fat embolism syndrome. SUMMARY OF REVIEW: Fat embolism occurs when
      bony or soft tissue trauma has caused fat to enter the circulation, or in
      atraumatic disorders where circulating fat particles have coalesced abnormally
      within the circulation. The fat particles deposit in the pulmonary and systemic
      circulations, although only 1 - 2% develop a clinical disorder with respiratory,
      cerebral and dermal manifestations known as the fat embolism syndrome. Rarely,
      fat embolism produces a fulminant fat embolism syndrome due to mechanical
      obstruction within the pulmonary circulation causing a severe right heart
      failure. The fat embolism syndrome is believed to be caused by the toxic effects
      of free fatty acids liberated at the endothelial layer which cause capillary
      disruption, perivascular haemorrhage and oedema. The clinical manifestations of
      respiratory failure, petechiae and a diffuse or focal cerebral disturbance, are
      characteristic but not pathognomonic of the syndrome. The syndrome is largely
      self limiting with treatment being symptomatic. Therapy is directed at
      maintaining respiratory function and largely follows the same principles of
      management used in patients who have the acute respiratory distress syndrome.
      Early immobilization of fractures and methods to reduce the intramedullary
      pressure during total hip arthroplasty have reduced the incidence of operative
      fat embolisation. Corticosteroids either before or after the development of
      respiratory or cerebral symptoms have not been shown to be of any benefit.
      CONCLUSIONS: Fat embolism occurs in many traumatic and atraumatic conditions and
      is largely asymptomatic. Preventative measures include early immobilization of
      fractures and methods to reduce intramedullary pressure during surgical
      manoeuvres. Treatment is largely symptomatic with therapy for respiratory failure
      similar to that used in management of acute respiratory distress syndrome.
      Corticosteroids have not been found to be of significant benefit.

PMID- 16603017
TI  - Delayed dissection of the internal carotid artery following major facial trauma:
      a case report.
AB  - Dissection of the internal carotid artery is often caused by trauma to the face
      or neck. It usually has a delayed onset neurological presentation, a partial
      middle cerebral artery territory syndrome, 'normal' early CT scan, MRI evidence
      of middle cerebral artery occlusion, progressive partial or complete neurological
      recovery, and duplex scan evidence of a reestablished lumen in the internal
      carotid artery after 10 weeks. A case is reported of a dissection of the right
      internal carotid artery in a patient with severe facial trauma. The patient
      presented with a left sided hemiplegia 8 hours after a motor vehicle accident. A
      cerebral CT scan performed 16 hours after the accident revealed a small wedge
      shaped area of cerebral infarction within the right temporo-parietal region. An
      MRI angiogram performed four days after the accident revealed a right carotid
      artery dissection with an occlusive thrombus of the dissected portion of the
      right internal carotid artery and right middle cerebral artery and a haemorrhagic
      infarct of the right parieto-occipital lobe. The patient was anticoagulated and
      over the next two weeks made a slow recovery, using her left hand effectively and
      walking unaided. Four months after the accident a duplex scan revealed that the
      right carotid artery lumen was patent with normal arterial flows. Five months
      after the accident the patient had returned to work.

PMID- 16603018
TI  - An unusual case of post operative nausea, vomiting and neck pain.
AB  - A case is described of subarachnoid haemorrhage caused by vertebral artery
      dissection following general anaesthesia for laparoscopic cholecystectomy. It is
      postulated that the dissection may have been a result of neck manipulation during
      intubation or other movements whilst paralysed, or alternatively, due to intra
      operative blood pressure changes occurring in a patient with a predisposition to
      arterial disruption. The case highlights the important symptom of neck pain in a
      patient with an intracranial catastrophe. Fortunately, despite a dramatic
      clinical presentation her recovery has been good.

PMID- 16603019
TI  - Echocardiography in intensive care: the basics. Part I.
AB  - OBJECTIVE: To review the current status of echocardiography in critically ill
      patients with special reference to the advantages and disadvantages of the
      transthoracic and transoesophageal approaches. DATA SOURCES: A review of articles
      published in peer reviewed journals from 1976-1999 and identified through a
      MEDLINE search on echocardiography. SUMMARY OF REVIEW: Echocardiography uses the
      reflection of high frequency sound waves at tissue boundaries to construct a two
      dimensional image of cardiac structures. Two-dimensional echo-cardiography is the
      cornerstone of cardiac ultrasound, although Doppler techniques (pulsed wave,
      continuous wave, and colour flow) form an integral part of every modern
      echocardiographic study. The Doppler effect is based on changes in sound
      frequency that occur when a sound source moves towards or away from an observer.
      Blood flow velocities measured by Doppler can be used to estimate pressure, valve
      area and stroke volume. The standard imaging positions of the probe are either
      outside the thorax (i.e. transthoraracic echocardiography or TTE) or inside the
      oesophagus (i.e. transoesophageal echo-cardiography or TOE) both of which provide
      information that can be helpful in managing critically ill patients. CONCLUSIONS:
      Echocardiography is a rapidly developing technology. Cardiac structures can be
      imaged in 'real time'. Image quality continues to improve. The use of
      transoesophageal probe positioning has also widened the potential of this bedside
      technique in critically ill patients.

PMID- 16603020
TI  - Echocardiography in Intensive Care: The Basics. Part II.
AB  - OBJECTIVE: To review the current status of echocardiography in critically ill
      patients with special reference to the advantages and disadvantages of the
      transthoracic and transoesophageal approaches. DATA SOURCES: A review of articles
      published in peer reviewed journals from 1976-1999 and identified through a
      MEDLINE search on echocardiography. SUMMARY OF REVIEW: Echocardiography is a
      rapidly evolving field which is relatively new to intensivists. Both
      transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE)
      are extremely useful in managing critically ill patients. In intensive care
      practice echocardiograpy is used to evaluate clinical syndromes such as
      unexplained hypotension, search for source of sepsis or source of emboli, as well
      as haemodynamic assessment and monitoring. TOE although somewhat invasive,
      provides superb images which often assist in both diagnosis and improved
      treatment. CONCLUSIONS: Echocardiography often provides useful information in
      critically ill patients. Intensivists should familiarise themselves with this new
      technology and if possible become skilled practitioners of this exciting
      technique. The care of critically ill patients will benefit from its widespread
      use.

PMID- 16603021
TI  - Volume state control - a new approach.
AB  - OBJECTIVE: To describe a new approach to circulating volume control in critically
      ill patients. DATA SOURCES: Studies in circulatory physiology, mathematical
      models of the circulation and open and closed loop circulation control. SUMMARY
      OF REVIEW: In evaluation of the volume state it may be Wiser to consider the
      determinants of the systemic venous return rather than those of the cardiac
      output. These determinants include the mean systemic filling pressure, the right
      atrial pressure and the unknown resistance to venous return. A model based
      approach is advanced to determine a mean systemic filling pressure analogue
      (P(msa)) which accounts for variation in venous resistance. It is suggested that
      P(msa) is an appropriate object of volume control. Definition of a volume state
      provides insights for cardioactive therapy. CONCLUSIONS: Use of a P(msa) volume
      signal enables prolonged stable closed loop volume servocontrol. In global heart
      dysfunction the dimensionless variable (P(msa )- RAP)/P(msa )may be used to guide
      inotropic therapy.

PMID- 16603023
TI  - "Shh! I think it's the patient" - again.

PMID- 16603022
TI  - Thinking in the critical care unit.

PMID- 16603024
TI  - Magnesium, malignant hyperpyrexia and a veterinary experience.

PMID- 16603025
TI  - Liver breath tests non-invasively predict higher stages of non-alcoholic
      steatohepatitis.
AB  - Effectively assessing subtle hepatic metabolic functions by novel non-invasive
      tests might be of clinical utility in scoring NAFLD (non-alcoholic fatty liver
      disease) and in identifying altered metabolic pathways. The present study was
      conducted on 39 (20 lean and 19 obese) hypertransaminasemic patients with
      histologically proven NAFLD {ranging from simple steatosis to severe
      steatohepatitis [NASH (non-alcoholic steatohepatitis)] and fibrosis} and 28 (20
      lean and eight overweight) healthy controls, who underwent stable isotope breath
      testing ([(13)C]methacetin and [(13)C]ketoisocaproate) for microsomal and
      mitochondrial liver function in relation to histology, serum hyaluronate, as a
      marker of liver fibrosis, and body size. Compared with healthy subjects and
      patients with simple steatosis, NASH patients had enhanced methacetin
      demethylation (P=0.001), but decreased (P=0.001) and delayed (P=0.006)
      ketoisocaproate decarboxylation, which was inversely related (P=0.001) to the
      degree of histological fibrosis (r=-0.701), serum hyaluronate (r=-0.644) and body
      size (r=-0.485). Ketoisocaproate decarboxylation was impaired further in obese
      patients with NASH, but not in patients with simple steatosis and in overweight
      controls. NASH and insulin resistance were independently associated with an
      abnormal ketoisocaproate breath test (P=0.001). The cut-off value of 9.6%
      cumulative expired (13)CO(2) for ketoisocaproate at 60 min was associated with
      the highest prediction (positive predictive value, 0.90; negative predictive
      value, 0.73) for NASH, yielding an overall sensitivity of 68% and specificity of
      94%. In conclusion, both microsomal and mitochondrial functions are disturbed in
      NASH. Therefore stable isotope breath tests may usefully contribute to a better
      and non-invasive characterization of patients with NAFLD.

PMID- 16603026
TI  - Use of the prone position in the acute respiratory distress syndrome: how should
      we assess benefit?
AB  - Prone positioning of patients with acute respiratory failure was first suggested
      over 30 years ago. In the present issue of Clinical Science, Reutershan and co
      workers have studied the changes in end-expiratory lung volume in 12 patients
      with ARDS (acute respiratory distress syndrome) over an 8 h period following
      manual turning from the supine to prone position. From the data presented, the
      authors suggest that baseline end-expiratory lung volume could be used to
      identify responders, and serial measurements would permit appropriate 'dosing' of
      the therapy. Although this is an interesting study that provides data that have
      rarely been collected when assessing the response to prone positioning, there are
      a number of limitations that need to be considered. However, despite the
      limitations, the study does stimulate a number of important questions related not
      only to the use of the prone position, but also to the management of patients
      with ARDS in general.

PMID- 16603027
TI  - Abstracts of the Annual Scientific Meeting of the Australasian College for
      Emergency Medicine 2005.

PMID- 16603028
TI  - Do schizoaffective disorders exist at all?

PMID- 16603029
TI  - Prevalence and predictors of depression in populations of elderly: a review.
AB  - OBJECTIVE: To offer an update on prevalence and predictors of old age depression
      in populations of elderly Caucasians. METHOD: The databases MEDLINE and Psychinfo
      were searched and relevant literature from 1993 onwards was reviewed. RESULTS:
      The prevalence of major depression ranges from 0.9% to 9.4% in private
      households, from 14% to 42% in institutional living, and from 1% to 16% among
      elderly living in private households or in institutions; and clinically relevant
      depressive symptom 'cases' in similar settings vary between 7.2% and 49%. The
      main predictors of depressive disorders and depressive symptom cases are: female
      gender, somatic illness, cognitive impairment, functional impairment, lack or
      loss of close social contacts, and a history of depression. CONCLUSION:
      Depression is frequent in populations of elderly. Methodological differences
      between the studies hinder consistent conclusions about geographical and cross
      cultural variations in prevalence and predictors of depression. Improved
      comparability will provide a basis for consistent conclusions.

PMID- 16603030
TI  - The state of mental health in old-age across the 'old' European Union-- a
      systematic review.
AB  - OBJECTIVE: The paper provides the first syllabus on the prevalence of mental
      disorders in old-age focusing on surveys conducted in the 15 countries, which
      comprised the 'old' European Union. METHOD: A systematic search of the literature
      published from 1990 onwards was conducted. RESULTS: Mental disorders in old-age
      are common. The most serious threats to mental health in old-age are posed by
      dementia and depression. It is a clear cut finding that dementia exponentially
      increases with age. The basic issue of whether depression increases or decreases
      with age remains unsolved. Databases on substance use, mild cognitive impairment,
      psychotic syndromes, anxiety, and somatoform disorders in old-age are much
      smaller, making conclusions difficult to draw. CONCLUSION: Numerous questions in
      the field remain to be answered. Concerted action is needed to produce comparable
      data across Europe.

PMID- 16603031
TI  - Schizoaffective disorder-- the reliability of its clinical diagnostic use.
AB  - OBJECTIVE: Patients with psychoses often suffer from affective symptoms. The
      originally broad concept of schizoaffective disorder (SAD) has been significantly
      narrowed, transformed into a convoluted set of criteria both in the ICD-10 and
      DSM-IV. We examined the reliability of the clinical use of this diagnosis in
      university settings. METHOD: All patients discharged from two university
      hospitals in Copenhagen in year 2002 with a diagnosis of ICD-10 SAD (n = 59) were
      re-evaluated using the Operational Criteria (OPCRIT) checklist expanded by
      additional items and applied to hospital chart material. Diagnoses were allocated
      by OPCRIT algorithm and by consensus of two psychiatrists. RESULTS: No patients
      fulfilled the SAD lifetime diagnosis according to DSM-IV criteria and the raters
      diagnosed only six patients as possible ICD-10 SAD. CONCLUSION: A moratorium on
      the clinical use of the SAD diagnosis is suggested.

PMID- 16603032
TI  - Cognitive behaviour therapy and medication in the treatment of obsessive
      compulsive disorder.
AB  - OBJECTIVE: To compare cognitive behaviour therapy (CBT) with CBT plus medication;
      medication alone; and placebo in the treatment of adult obsessive-compulsive
      disorder (OCD). METHOD: Forty-eight participants (43 completers) were recruited
      into two protocols. In the first protocol, 21 people with OCD were randomly
      allocated to either a standard medication (fluvoxamine) or standard placebo
      condition for a 5-month period. Both these groups subsequently received CBT for a
      further 5 months. In the second protocol, 22 people with OCD received CBT, one
      group was already stabilized on an antidepressant of choice; the second group was
      drug naive. RESULTS: All active treatments, but not the placebo, showed clinical
      improvement. There was no difference in treatment response to CBT regardless of
      whether participants had previously received medication or placebo. CONCLUSION:
      CBT has a more specific antiobsessional effect than medication but CBT plus
      medication shows greatest overall clinical improvement in mood.

PMID- 16603033
TI  - Altered neural circuit for working memory before and after symptom provocation in
      patients with obsessive-compulsive disorder.
AB  - OBJECTIVE: The authors compared the neural circuits recruited for working memory
      (WM) in obsessive-compulsive disorder (OCD) patients both at a neutral state and
      at a symptom provoked state. METHOD: Twelve OCD patients, and 12 age-, and sex
      matched healthy subjects underwent [(15)O]H(2)O positron emission tomography
      (PET) scanning, while performing WM task. In the patients, the tasks were
      performed both in the neutral and in the symptom provoked states. RESULTS: In the
      OCD patients, the right caudate and the right superior parietal cortex (rSPC)
      displayed activations for WM at the neutral state, while the right cingulate
      cortex and rSPC displayed activations for WM at the symptom provoked state. Path
      analysis revealed that the activity of the caudate and orbitofrontal cortex was
      altered according to the interaction between WM and symptom provocation.
      CONCLUSION: The interaction between symptom provocation and WM occurring in the
      fronto-striatal system may hold the key to the neurobiology of OCD.

PMID- 16603035
TI  - Symptom dimensions in obsessive-compulsive disorder: prediction of cognitive
      behavior therapy outcome.
AB  - OBJECTIVE: A significant number of patients with obsessive-compulsive disorder
      (OCD) fail to benefit sufficiently from treatments. This study aimed to evaluate
      whether certain OCD symptom dimensions were associated with cognitive-behavioral
      therapy (CBT) outcome. METHOD: Symptoms of 104 CBT-treated in-patients with OCD
      were assessed with the clinician-rated Yale-Brown Obsessive-Compulsive Scale
      symptom checklist. Logistic regression analyses examined outcome predictors.
      RESULTS: The most frequent OCD symptoms were aggressive and contamination
      obsessions, and compulsive checking and cleaning. Patients with hoarding symptoms
      at baseline (n = 19) were significantly less likely to become treatment
      responders as compared to patients without these symptoms. Patients with sexual
      and religious obsessions tended to respond less frequently, although this failed
      to reach statistical significance (P = 0.07). Regression analyses revealed that
      higher scores on the hoarding dimension were predictive of non-response, even
      after controlling for possible confounding variables. CONCLUSION: Our results
      strongly indicate that in-patients with obsessive-compulsive hoarding respond
      poorly to CBT.

PMID- 16603034
TI  - Hierarchical relationships between borderline, schizotypal, avoidant and
      obsessive-compulsive personality disorders.
AB  - OBJECTIVE: Comorbidity among personality disorders is widely considered
      problematic. The validity of one proposed solution, diagnostic hierarchies, was
      investigated in the current study with respect to borderline, schizotypal,
      avoidant, and obsessive-compulsive personality disorders. METHOD: One approach
      used discriminant functions, derived from multiple psycho-social domains, that
      were used to classify comorbid individuals from the Collaborative Longitudinal
      Personality Disorder study (CLPS) to explore the possibility of hierarchical
      precedence of one personality disorder over another. A second approach examined
      the incremental increase in R(2)-value in predicting functioning and personality
      provided by each diagnosis over each other diagnosis. RESULTS: Obsessive
      compulsive personality disorder was consistently subordinate to other diagnoses,
      whereas other indications of hierarchical relationships were domain-specific.
      CONCLUSION: Results indicate minimal support for an over-arching hierarchical
      pattern among studied personality disorders, and suggest the inclusion of all
      relevant diagnoses in clinical practice.

PMID- 16603040
TI  - The management of periapical lesions in endodontically treated teeth.
AB  - When root canal therapy is done according to accepted clinical principles and
      under aseptic conditions, the success rate is generally high. However, it has
      also been reported that 16% to 64.5% of endodontically treated teeth are
      associated with periapical radiolucent lesions. There are great variations among
      clinicians when suggesting treatment of these failed endodontic cases. This
      article will discuss factors influencing treatment decisions on these particular
      cases, and the pros and cons of nonsurgical retreatment versus surgical
      retreatment. The advancement of modern endodontic microsurgery will also be
      discussed.

PMID- 16603041
TI  - Determination of root canal curvatures before and after canal preparation (part
      II): A method based on numeric calculus.
AB  - The aim of this paper is to present a new method based on numeric calculus to
      provide data on any type of root canal curvature at any point of the long axis of
      the canal. Twenty severely curved, simulated root canals were prepared with
      rotary FlexMaster and Profile instruments in the crown-down technique and
      manually in the step-back technique. The inner and outer curvatures were
      registered in a system of coordinates before and after preparation in increments
      of 0.5 mm. Using an equalising function, the curvatures were first represented in
      graphic and algebraic form. The maximum and the mean curvature as well as the
      length of the arc from the apical foramen to the point of maximum curvature were
      determined mathematically. An increase in maximum curvature was registered for
      all four shaping systems investigated. The radius of the inner curvature
      decreased by 0.5-1.2 mm in the manual systems as a result of the preparation. The
      Profile system displayed the smallest changes in radius (-0.9 mm) even with the
      outer curvature, and manual preparation with stainless steel files the most
      pronounced change (-1.8 mm). The point of maximum curvature at the inner
      curvature was displaced by 1.6 mm to the apical foramen through manual
      preparation with Ni-Ti files. At the outer curvature, the maximum displacement
      (1.8 mm) recorded was also the result of preparation with Ni-Ti hand files, while
      a displacement of only 0.3 mm to the apical foramen was recorded with the other
      systems. The method offers a means of determining curvatures precisely without
      random specification of reference points. The method is also capable of
      registering only minor changes in curvature in the two-dimensional long axis of
      the canal.

PMID- 16603042
TI  - SEM evaluation of neodentinal bridging after direct pulp protection with mineral
      trioxide aggregate.
AB  - The purpose of this study was to observe the basic morphology and determine the
      chemical composition of neodentinal bridges adjacent white mineral trioxide
      aggregate (WMTA) when used as a direct pulp capping material. The experimental
      procedures were performed on six intact dogs' teeth. The pulps were exposed and
      cavities were filled with WMTA. After 2 weeks, neodentinal bridge formation was
      evaluated by scanning electron microscope (SEM) of cross-sections of the
      specimens and electron probe microanalysis (EPMA) of the pulpal surfaces. Results
      of SEM observation showed that the most characteristic reaction of pulp cells was
      the intimate connection of cell processes and secreted extracellular fibres with
      the crystals of the pulp capping material. Results of EPMA indicated that the
      mineralisation of neodentinal bridge formation occurred progressively from the
      periphery to the central area. Based on these results, it appears that WMTA has
      the potential to be used as a direct pulp capping material during vital pulp
      therapy.

PMID- 16603043
TI  - Radiographic and rheological properties of a new endodontic sealer.
AB  - A new dual-cured resin sealer has recently been proposed as an innovative
      endodontic filling material. Being a new endodontic material, no in vitro
      research has been published yet on Real Seal's (RS) physical properties.
      Therefore, the aim of the present study was to evaluate and compare radiopacity
      and rheological properties of the RS sealer with those of currently available
      endodontic sealers (Roeko Seal Automix and Bioseal). All tests strictly followed
      American National Standards Institute/American Dental Association (ANSI/ADA)
      specification No. 57, which indicates test methods and establishes minimal
      requirements of flow, film thickness and radiopacity of endodontic sealers.
      Results showed that significant differences were found among sealers in the
      different test methods. However, RS showed values complying with ANSI/ADA
      specification No. 57 requirements in all tests. Hence, the new RS sealer
      exhibited radiographic and rheological properties suitable for clinical use.

PMID- 16603044
TI  - Effect of Waterlase laser retrograde root-end cavity preparation on the integrity
      of root apices of extracted teeth as demonstrated by light microscopy.
AB  - Most endodontists use ultrasonic instruments for retrograde root-end cavity
      preparations even though they have been found to produce cracks. In this
      laboratory study, thirty-six randomly chosen roots had root-end cavity
      preparations made with the Waterlase laser and only one questionable intra-canal
      crack was found. It was concluded that the Waterlase laser when used to make
      endodontic root-end cavity preparations produces either no cracks, or a very low
      percentage (2.8%) of cracks.

PMID- 16603045
TI  - Endodontic therapy on a dentition exhibiting multiple periapical radiolucencies
      associated with dentinal dysplasia Type 1.
AB  - Dentinal dysplasia (DD) Type I, is a hereditary disturbance in dentine formation.
      In this anomaly, teeth in both primary and secondary dentitions are affected, and
      radiographically show short and blunted roots with obliterated root canals and
      periapical pathosis. Management of patients with DD has presented dentists with
      problems. Extraction has been suggested as a treatment alternative for teeth with
      pulp necrosis and periapical abscess. Follow-up and routine conservative
      treatment is another choice of treatment plan in DD. Another approach for the
      treatment of teeth with DD has included periapical surgery and retrograde
      filling, which is recommended in the teeth with long roots. The purpose of this
      report is to present an unusual case of dentinal dysplasia Type I in a 22-year
      old woman showing upper and lower teeth with obliterated root canals and
      periapical radiolucencies. In this case, conventional endodontic treatment was
      performed. Postoperative radiographs and clinical evaluation demonstrated
      periapical healing and successful results. Based on the results of this case
      report, conventional endodontic treatment for cases with pulp necrosis and
      periapical radiolucencies in dentinal dysplasia is highly recommended.

PMID- 16603046
TI  - Unusual anatomy of mandibular premolars.
AB  - Mandibular premolars usually have a single root and canal; however, during
      clinical and radiographic evaluation as part of endodontic treatment it must be
      noted that variations in anatomical configuration are not uncommon. These teeth
      may require special canal preparation and filling techniques. This article
      discusses the treatment recommendations for unusual anatomical configurations in
      two different mandibular premolars and reports the treatment carried out on these
      teeth.

PMID- 16603050
TI  - Periapicitis.

PMID- 16603051
TI  - Calcium hydroxide and zinc oxide eugenol as root canal filling materials.

PMID- 16603053
TI  - A hospital-based surveillance for Japanese encephalitis in Bali, Indonesia.
AB  - BACKGROUND: Japanese encephalitis (JE) is presumed to be endemic throughout Asia,
      yet only a few cases have been reported in tropical Asian countries such as
      Indonesia, Malaysia and the Philippines. To estimate the true disease burden due
      to JE in this region, we conducted a prospective, hospital-based surveillance
      with a catchment population of 599,120 children less than 12 years of age in
      Bali, Indonesia, from July 2001 through December 2003. METHODS: Balinese children
      presenting to any health care facility with acute viral encephalitis or aseptic
      meningitis were enrolled. A "confirmed" diagnosis of JE required the detection of
      JE virus (JEV)-specific IgM in cerebrospinal fluid, whereas a diagnosis of
      "probable JE" was assigned to those cases in which JEV-specific IgM was detected
      only in serum. RESULTS: In all, 86 confirmed and 4 probable JE cases were
      identified. The annualized JE incidence rate was 7.1 and adjusted to 8.2 per
      100,000 for children less than 10 years of age over the 2.5 consecutive years of
      study. Only one JE case was found among 96,920 children 10-11 years old (0.4 per
      100,000). Nine children (10%) died and 33 (37%) of the survivors had neurological
      sequelae at discharge. JEV was transmitted in Bali year-round with 70% of cases
      in the rainy season. CONCLUSION: JE incidence and case-fatality rates in Bali
      were comparable to those of other JE-endemic countries of Asia. Our findings
      contradict the common wisdom that JE is rare in tropical Asia. Hence, the
      geographical range of endemic JE is broader than previously described. The
      results of the study support the need to introduce JE vaccination into Bali.

PMID- 16603054
TI  - Short term culture of breast cancer tissues to study the activity of the
      anticancer drug taxol in an intact tumor environment.
AB  - BACKGROUND: Sensitivity of breast tumors to anticancer drugs depends upon dynamic
      interactions between epithelial tumor cells and their microenvironment including
      stromal cells and extracellular matrix. To study drug-sensitivity within
      different compartments of an individual tumor ex vivo, culture models directly
      established from fresh tumor tissues are absolutely essential. METHODS: We
      prepared 0.2 mm thick tissue slices from freshly excised tumor samples and
      cultivated them individually in the presence or absence of taxol for 4 days. To
      visualize viability, cell death, and expression of surface molecules in different
      compartments of non-fixed primary breast cancer tissues we established a method
      based on confocal imaging using mitochondria- and DNA-selective dyes and
      fluorescent-conjugated antibodies. Proliferation and apoptosis was assessed by
      immunohistochemistry in sections from paraffin-embedded slices. Overall viability
      was also analyzed in homogenized tissue slices by a combined ATP/DNA
      quantification assay. RESULTS: We obtained a mean of 49 tissue slices from 22
      breast cancer specimens allowing a wide range of experiments in each individual
      tumor. In our culture system, cells remained viable and proliferated for at least
      4 days within their tissue environment. Viability of tissue slices decreased
      significantly in the presence of taxol in a dose-dependent manner. A three-color
      fluorescence viability assay enabled a rapid and authentic estimation of cell
      viability in the different tumor compartments within non-fixed tissue slices.
      CONCLUSION: We describe a tissue culture method combined with a novel read out
      system for both tissue cultivation and rapid assessment of drug efficacy together
      with the simultaneous identification of different cell types within non-fixed
      breast cancer tissues. This method has potential significance for studying tumor
      responses to anticancer drugs in the complex environment of a primary cancer
      tissue.

PMID- 16603055
TI  - Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome
      amongst the Taiwanese population- not correlated with insulin receptor substrate
      1 Gly972Arg/Ala513Pro polymorphism.
AB  - BACKGROUND: Insulin resistance and glucose dysmetabolism in polycystic ovary
      syndrome (PCOS) are related with the polymorphisms in the genes encoding the
      insulin receptor substrate (IRS) proteins, especially Gly972Arg/Ala513Pro
      polymorphism being reported to be associated with type-2 diabetes and PCOS. We
      intended to assess the prevalence of abnormal glucose tolerance (AGT) and insulin
      resistance in Taiwanese PCOS women. We also tried to assess whether the
      particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene
      mutation can be used as an appropriate diagnostic indicator for PCOS. METHODS: We
      designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka
      women, diagnosed with PCOS were enrolled in this study as were forty-five healthy
      Hoklo and Hakka women as the control group. Insulin resistance was evaluated with
      fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment
      index for insulin resistance (HOMAIR). The genomic DNA of the subjects was
      amplified by PCR and digested by restriction fragmented length polymorphism
      (RFLP) with Bst N1 used for codon 972 and Dra III for codon 513. RESULTS: AGT was
      found in 46.8% of these PCOS patients and was significantly related to high
      insulin resistance rather than the low insulin resistance. Those patients with
      either insulin resistance or AGT comprised the majority of PCOS affected patients
      (AGT + fasting insulin > or =17: 83%, AGT + glucose/insulin ratio > or =6.5:
      85.1%, AGT + HOMAIR > or = 2: 87.2%, and AGT + HOMAIR > or = 3.8: 72.3%). None of
      the tested samples revealed any polymorphism due to the absence of any Dra III
      recognition site or any Bst N1 recognition site in the amplified PCR fragment
      digested by restriction fragmented length polymorphism. CONCLUSION: There is
      significantly high prevalence of AGT and insulin resistance in PCOS women, but
      Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not
      associated with the elevated risk of PCOS amongst Taiwanese subjects. This is
      quite different from the similar study in phylogenetically diverged Caucasian
      subjects.

PMID- 16603056
TI  - Severe airway stenosis associated with Crohn's disease: case report.
AB  - BACKGROUND: Symptomatic respiratory tract involvement is not common in Crohn's
      disease. Upper-airway obstruction has been reported before in Crohn's disease and
      usually responds well to steroid treatment. CASE PRESENTATION: We report a case
      of a 32-year old patient with Crohn's disease who presented with progressively
      worsening dyspnea on exertion. Magnetic Resonance Imaging of the chest and
      bronchoscopy revealed severe tracheal stenosis and marked inflammation of
      tracheal mucosa. Histopathology of the lesion showed acute and chronic
      inflammation and extended ulceration of bronchial mucosa, without granulomas.
      Tracheal stenosis was attributed to Crohn's disease after exclusion of other
      possible causes and oral and inhaled steroids were administered. Despite steroid
      treatment, tracheal stenosis persisted and only mild symptomatic improvement was
      noted after 8 months of therapy. The patient subsequently underwent rigid
      bronchoscopy with successful dilatation and ablation of the stenosed areas and
      remission of her symptoms. CONCLUSION: Respiratory involvement in Crohn's disease
      might be more common than appreciated. Interventional pulmonology techniques
      should be considered in cases of tracheal stenosis due to Crohn's disease
      refractory to steroid treatment.

PMID- 16603057
TI  - Efavirenz use during pregnancy and for women of child-bearing potential.
AB  - BACKGROUND: Efavirenz is the preferred non-nucleoside reverse transcriptase
      inhibitor for first-line antiretroviral treatment in many countries. For women of
      childbearing potential, advantages of efavirenz are balanced by concerns that it
      is teratogenic. This paper reviews evidence of efavirenz teratogenicity and
      considers implications in common clinical scenarios. FINDINGS: Concerns of
      efavirenz-induced fetal effects stem from animal studies, although the predictive
      value of animal data for humans is unknown. Four retrospective cases of central
      nervous system birth defects in infants with first trimester exposure to
      efavirenz have been interpreted as being consistent with animal data. In a
      prospective pregnancy registry, which is subject to fewer potential biases, no
      increase was detected in overall risk of birth defects following exposure to
      efavirenz in the first-trimester. DISCUSSION: For women planning a pregnancy or
      not using contraception, efavirenz should be avoided if alternatives are
      available. According to WHO guidelines for resource-constrained settings,
      benefits of efavirenz are likely to outweigh risks for women using contraception.
      Women who become pregnant while receiving efavirenz often consider drug
      substitution or temporarily suspending treatment. Both options have substantial
      risks for maternal and fetal health which, we argue, appear unjustified after the
      critical period of organogenesis (3-8 weeks post-conception). Efavirenz-based
      triple regimens, initiated after the first trimester of pregnancy and
      discontinued after childbirth, are potentially an important alternative for
      reducing mother-to-child transmission in pregnant women who do not yet require
      antiretroviral treatment. CONCLUSION: Current recommendations for care for women
      who become pregnant while receiving efavirenz may need to be re-considered,
      particularly in settings with limited alternative drugs and laboratory
      monitoring. With current data limitations, additional adequately powered
      prospective studies are needed.

PMID- 16603058
TI  - Fatigue Intervention by Nurses Evaluation--the FINE Trial. A randomised
      controlled trial of nurse led self-help treatment for patients in primary care
      with chronic fatigue syndrome: study protocol. [ISRCTN74156610].
AB  - BACKGROUND: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition
      characterised primarily by severe, disabling fatigue, of unknown origin, which
      has a poor prognosis and serious personal and economic consequences. Evidence for
      the effectiveness of any treatment for CFS/ME in primary care, where most
      patients are seen, is sparse. Recently, a brief, pragmatic treatment for CFS/ME,
      based on a physiological dysregulation model of the condition, was shown to be
      successful in improving fatigue and physical functioning in patients in secondary
      care. The treatment involves providing patients with a readily understandable
      explanation of their symptoms, from which flows the rationale for a graded
      rehabilitative plan, developed collaboratively with the therapist. The present
      trial will test the effectiveness and cost-effectiveness of pragmatic
      rehabilitation when delivered by specially trained general nurses in primary
      care. We selected a client-centred counselling intervention, called supportive
      listening, as a comparison treatment. Counselling has been shown to be as
      effective as cognitive behaviour therapy for treating fatigue in primary care, is
      more readily available, and controls for supportive therapist contact time. Our
      control condition is treatment as usual by the general practitioner (GP). METHODS
      AND DESIGN: This study protocol describes the design of an ongoing, single-blind,
      pragmatic randomized controlled trial of a brief (18 week) self-help treatment,
      pragmatic rehabilitation, delivered by specially trained nurse-therapists in
      patients' homes, compared with nurse-therapist delivered supportive listening and
      treatment as usual by the GP. An economic evaluation, taking a societal
      viewpoint, is being carried out alongside the clinical trial. Three adult general
      nurses were trained over a six month period to deliver the two interventions.
      Patients aged over 18 and fulfilling the Oxford criteria for CFS are assessed at
      baseline, after the intervention, and again one year later. Primary outcomes are
      self-reported physical functioning and fatigue at one year, and will be analysed
      on an intention-to-treat basis. A qualitative study will examine the
      interventions' mechanisms of change, and also GPs' drivers and barriers towards
      referral.

PMID- 16603060
TI  - An exploratory mixed methods study of the acceptability and effectiveness of
      Mindfulness-Based Cognitive Therapy for patients with active depression and
      anxiety in primary care.
AB  - BACKGROUND: Mindfulness Based Cognitive Therapy (MBCT) is an 8-week course
      developed for patients with relapsing depression that integrates mindfulness
      meditation practices and cognitive theory. Previous studies have demonstrated
      that non-depressed participants with a history of relapsing depression are
      protected from relapse by participating in the course. This exploratory study
      examined the acceptability and effectiveness of MBCT for patients in primary care
      with active symptoms of depression and anxiety METHODS: 13 patients with
      recurrent depression or recurrent depression and anxiety were recruited to take
      part in the study. Semi-structured qualitative interviews were conducted three
      months after completing the MBCT programme. A framework approach was used to
      analyse the data. Beck depression inventories (BDI-II) and Beck anxiety
      inventories (BAI) provided quantitative data and were administered before and
      three months after the intervention. RESULTS: The qualitative data indicated that
      mindfulness training was both acceptable and beneficial to the majority of
      patients. For many of the participants, being in a group was an important
      normalising and validating experience. However most of the group believed the
      course was too short and thought that some form of follow up was essential. More
      than half the patients continued to apply mindfulness techniques three months
      after the course had ended. A minority of patients continued to experience
      significant levels of psychological distress, particularly anxiety. Statistically
      significant reductions in mean depression and anxiety scores were observed; the
      mean pre-course depression score was 35.7 and post-course score was 17.8 (p =
      0.001). A similar reduction was noted for anxiety with a mean pre-course anxiety
      score of 32.0 and mean post course score of 20.5 (p = 0.039). Overall 8/11 (72%)
      patients showed improvements in BDI and 7/11 (63%) patients showed improvements
      in BAI. In general the results of the qualitative analysis agreed well with the
      quantitative changes in depression and anxiety reported. CONCLUSION: The results
      of this exploratory mixed methods study suggest that mindfulness based cognitive
      therapy may have a role to play in treating active depression and anxiety in
      primary care.

PMID- 16603061
TI  - Crystal engineering of analogous and homologous organic compounds: hydrogen
      bonding patterns in trimethoprim hydrogen phthalate and trimethoprim hydrogen
      adipate.
AB  - BACKGROUND: Trimethoprim [2,4-diamino-5-(3',4',5'-trimethoxybenzyl)pyrimidine] is
      an antifolate drug. It selectively inhibits the bacterial dihydrofolate reductase
      (DHFR) enzyme. RESULTS: In the crystal structures of trimethoprim (TMP)-hydrogen
      phthalate (1) and trimethoprim-hydrogen adipate (2), one of the N atoms of the
      pyrimidine ring is protonated and it interacts with the deprotonated carboxylate
      oxygens through a pair of nearly parallel N-H...O hydrogen bonds to form a fork
      like interaction. In the compound 1, the pyrimidine moieties of the TMP cations
      are centrosymmetrically paired through a pair of N-H...N hydrogen bonds involving
      4-amino group and the N (N3) atom of the pyrimidine rings to form a 8-membered
      hydrogen bonded ring [R2(2)(8)]. The 4-amino group of one TMP moiety and 2-amino
      group of another TMP moiety (both moieties are members of a base pair) are
      bridged by the carbonyl oxygen of the phthalate moiety through N-H...O hydrogen
      bonds forming 8-membered hydrogen-bonded ring [R2(2)(8)]. The characteristic
      hydrogen-bonded rings observed in the structure aggregate into a supramolecular
      ladder consisting of a pair of chains, each of which is built up of alternate TMP
      and hydrogen phthalate ions. In the compound 2, two TMP cations and two hydrogen
      adipate anions are arranged about an inversion center so that the complementary
      DDAA (D = donor, A = acceptor) arrays of quadruple hydrogen-bonding patterns are
      formed. The head-to-tail arrangement of the hydrogen adipate ions leads to a
      hydrogen-bonded supramolecular chain. From crystal engineering point of view, it
      is interesting to note that the compound 1 has a hydrogen-bonded network
      remarkably identical with its aliphatic analogue, trimethoprim hydrogen maleate.
      Similarly the compound 2, resembles its homolog trimethoprim hydrogen glutarate.
      CONCLUSION: In the crystal structure of trimethoprim hydrogen phthalate, the
      hydrogen-bonded network is remarkably identical with its aliphatic analogue,
      trimethoprim hydrogen maleate. Similarly in the crystal structure of trimethoprim
      hydrogen adipate the hydrogen bonded network resembles its homolog trimethoprim
      hydrogen glutarate.

PMID- 16603059
TI  - Retrograde transport pathways utilised by viruses and protein toxins.
AB  - A model has been presented for retrograde transport of certain toxins and viruses
      from the cell surface to the ER that suggests an obligatory interaction with a
      glycolipid receptor at the cell surface. Here we review studies on the ER
      trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A
      and ricin, and compare the retrograde routes followed by these protein toxins to
      those of the ER trafficking SV40 and polyoma viruses. We conclude that there is
      in fact no obligatory requirement for a glycolipid receptor, nor even with a
      protein receptor in a lipid-rich environment. Emerging data suggests instead that
      there is no common pathway utilised for retrograde transport by all of these
      pathogens, the choice of route being determined by the particular receptor
      utilised.

PMID- 16603062
TI  - Fine-needle aspiration of follicular lesions of the thyroid. Diagnosis and follow
      Up.
AB  - The differential diagnosis of a follicular lesion/neoplasm in thyroid FNA
      specimens includes hyperplastic/adenomatoid nodule, follicular adenoma and
      carcinoma, and follicular variant of papillary thyroid carcinoma. In our
      laboratory we separate follicular lesions of thyroid into
      hyperplastic/adenomatoid nodule (HN), follicular neoplasm (FON) and follicular
      derived neoplasm with focal nuclear features suspicious for papillary thyroid
      carcinoma (FDN). This study reports our experience with 339 cases diagnosed as
      FON and 120 as FDN. All cases were evaluated for histologic diagnosis, age, sex
      and size of the nodule. Histopathologic follow-up was available in all cases. The
      malignancy rate was 22% (74/359) and 72% (86/120) for cases diagnosed as FON and
      FDN, respectively. In the FON category almost half of the malignant cases were
      papillary carcinoma. The risk of malignancy was higher in patients younger than
      40 yr (53% vs. 30%) than in patients 40 year or more years old and greater in
      males (41% vs. 33%) than females. No statistically significant relationship was
      noted between the sizes of the nodules and benign vs. malignant diagnosis.
      According to this study it is important to divide follicular patterned lesions of
      thyroid into FON and FDN in the cytology specimens due to significantly different
      risk of malignancy (22% vs. 72%). In addition, clinical features, including
      gender and age can be part of the decision analysis in selecting patients for
      surgery.

PMID- 16603063
TI  - Health status measurement in COPD: the minimal clinically important difference of
      the clinical COPD questionnaire.
AB  - BACKGROUND: Patient-reported outcomes (PRO) questionnaires are being increasingly
      used in COPD clinical studies. The challenge facing investigators is to determine
      what change is significant, ie what is the minimal clinically important
      difference (MCID). This study aimed to identify the MCID for the clinical COPD
      questionnaire (CCQ) in terms of patient referencing, criterion referencing, and
      by the standard error of measurement (SEM). METHODS: Patients were > or = 40
      years of age, diagnosed with COPD, had a smoking history of >10 pack-years, and
      were participating in a randomized, controlled clinical trial comparing
      intravenous and oral prednisolone in patients admitted with an acute exacerbation
      of COPD. The CCQ was completed on Days 1-7 and 42. A Global Rating of Change
      (GRC) assessment was taken to establish the MCID by patient referencing. For
      criterion referencing, health events during a period of 1 year after Day 42 were
      included in this analysis. RESULTS: 210 patients were recruited, 168 completed
      the CCQ questionnaire on Day 42. The MCID of the CCQ total score, as indicated by
      patient referencing in terms of the GRC, was 0.44. The MCID of the CCQ in terms
      of criterion referencing for the major outcomes was 0.39, and calculation of the
      SEM resulted in a value of 0.21. CONCLUSION: This investigation, which is the
      first to determine the MCID of a PRO questionnaire via more than one approach,
      indicates that the MCID of the CCQ total score is 0.4.

PMID- 16603064
TI  - Inhibition of histone deacetylation in 293GPG packaging cell line improves the
      production of self-inactivating MLV-derived retroviral vectors.
AB  - BACKGROUND: Self-inactivating retroviral vectors (SIN) are often associated with
      very low titers. Promoter elements embedded within SIN designs may suppress
      transcription of packageable retroviral RNA which in turn results in titer
      reduction. We tested whether this dominant-negative effect involves histone
      acetylation state. We designed an MLV-derived SIN vector using the
      cytomegalovirus immediate early enhancer-promoter (CMVIE) as an embedded internal
      promoter (SINCMV) and transfected the pantropic 293GPG packaging cell line.
      RESULTS: The SINCMV retroviral producer had uniformly very low titers
      (approximately 10,000 infectious retroparticles per ml). Northern blot showed low
      levels of expression of retroviral mRNA in producer cells in particular that of
      packageable RNA transcript. Treatment of the producers with the histone
      deacetylase (HDAC) inhibitors sodium butyrate and trichostatin A reversed
      transcriptional suppression and resulted in an average 106.3 +/- 4.6 - fold (P =
      0.002) and 15.5 +/- 1.3 - fold increase in titer (P = 0.008), respectively. A
      histone gel assay confirmed increased histone acetylation in treated producer
      cells. CONCLUSION: These results show that SIN retrovectors incorporating strong
      internal promoters such as CMVIE, are susceptible to transcriptional silencing
      and that treatment of the producer cells with HDAC inhibitors can overcome this
      blockade suggesting that histone deacetylation is implicated in the mechanism of
      transcriptional suppression.

PMID- 16603065
TI  - The chrondoprotective actions of a natural product are associated with the
      activation of IGF-1 production by human chondrocytes despite the presence of IL
      1beta.
AB  - BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of
      catabolic processes concomitant with a disruption of anabolic pathways like
      insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products
      of South American origin, would limit cartilage degradation by respectively
      suppressing catabolism and activating local IGF-1 anabolic pathways. One extract,
      derived from cat's claw (Uncaria guianensis, vincaria), is a well-described
      inhibitor of NF-kappaB. The other extract, derived from the vegetable Lepidium
      meyenii (RNI 249), possessed an uncertain mechanism of action but with defined
      ethnomedical applications for fertility and vitality. METHODS: Human cartilage
      samples were procured from surgical specimens with consent, and were evaluated
      either as explants or as primary chondrocytes prepared after enzymatic digestion
      of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production
      (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under
      basal conditions and in the presence of IL-1beta. RESULTS: RNI 249 enhanced basal
      IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further
      enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1
      production by RNI 249 alone and together with vincaria, was confirmed in both
      explants and in primary chondrocytes (P < 0.05). As expected, IL-1beta exposure
      completely silenced IGF-1 production by chondrocytes. However, in the presence of
      IL-1beta both RNI 249 and vincaria protected IGF-1 production in an additive
      manner (P < 0.01) with the combination restoring chondrocyte IGF-1 production to
      normal levels. Cartilage NO production was dramatically enhanced by IL-1beta.
      Both vincaria and RNI 249 partially attenuated NO production in an additive
      manner (p < 0.05). IL-1beta - induced degradation of cartilage matrix was
      quantified as glycosaminoglycan release. Individually RNI 249 or vincaria,
      prevented this catabolic action of IL-1beta. CONCLUSION: The identification of
      agents that activate the autocrine production of IGF-1 in cartilage, even in the
      face of suppressive pro-inflammatory, catabolic cytokines like IL-1beta,
      represents a novel therapeutic approach to cartilage biology. Chondroprotection
      associated with prevention of the catabolic events and the potential for
      sustained anabolic activity with this natural product suggests that it holds
      significant promise in the treatment of debilitating joint diseases.

PMID- 16603066
TI  - The permeability of SPION over an artificial three-layer membrane is enhanced by
      external magnetic field.
AB  - BACKGROUND: Sensorineural hearing loss, a subset of all clinical hearing loss,
      may be correctable through the use of gene therapy. We are testing a delivery
      system of therapeutics through a 3 cell-layer round window membrane model (RWM
      model) that may provide an entry of drugs or genes to the inner ear. We designed
      an in vitro RWM model similar to the RWM (will be referred to throughout the
      paper as RWM model) to determine the feasibility of using superparamagnetic iron
      oxide (Fe3O4) nanoparticles (SPION) for targeted delivery of therapeutics to the
      inner ear. The RWM model is a 3 cell-layer model with epithelial cells cultured
      on both sides of a small intestinal submucosal (SIS) matrix and fibroblasts
      seeded in between. Dextran encapsulated nanoparticle clusters 130 nm in diameter
      were pulled through the RWM model using permanent magnets with flux density 0.410
      Tesla at the pole face. The SIS membranes were harvested at day 7 and then fixed
      in 4% paraformaldehyde. Transmission electron microscopy and fluorescence
      spectrophotometry were used to verify transepithelial transport of the SPION
      across the cell-culture model. Histological sections were examined for evidence
      of SPION toxicity, as well to generate a timeline of the position of the SPION at
      different times. SPION also were added to cells in culture to assess in vitro
      toxicity. RESULTS: Transepithelial electrical resistance measurements confirmed
      epithelial confluence, as SPION crossed a membrane consisting of three co
      cultured layers of cells, under the influence of a magnetic field. Micrographs
      showed SPION distributed throughout the membrane model, in between cell layers,
      and sometimes on the surface of cells. TEM verified that the SPION were pulled
      through the membrane into the culture well below. Fluorescence spectrophotometry
      quantified the number of SPION that went through the SIS membrane. SPION showed
      no toxicity to cells in culture. CONCLUSION: A three-cell layer model of the
      human round window membrane has been constructed. SPION have been magnetically
      transported through this model, allowing quantitative evaluation of prospective
      targeted drug or gene delivery through the RWM. Putative in vivo carrier
      superparamagnetic nanoparticles may be evaluated using this model.

PMID- 16603067
TI  - An unusual cause of acute abdominal pain - a case presentation.
AB  - BACKGROUND: In 1983, Graham Hughes described a condition of Antiphospholipid
      Syndrome in which there was a danger of thrombosis. The condition is readily
      detectable by blood tests and, once diagnosed; the risk of further thrombosis can
      be significantly reduced by anticoagulation treatments. Affected groups of
      patients can be distinguished by a specific blood test - the detection of
      antiphospholipid antibody (Ref-1). Patients with Hughes syndrome have
      hypercoaguable state with a markedly increased risk of both arterial and venous
      thrombosis and there is temporal persistence of antibody positivity. CASE
      PRESENTATION: A 44-year-old woman was admitted under the acute surgical "take"
      with left sided abdominal pain radiating to her back. She had a history of
      borderline thyrotoxicosis in the early 1990s. She was on etonogestrel-releasing
      implants for contraception and there was no history of previous deep venous
      thrombosis. She was very tender, locally, over the left side of the abdomen.
      Investigations showed haemoglobin of 13.2 g/dl, white cell count of 19.9 10*9/L,
      and platelets 214 10*9/L with neutrophilia. Amylase and renal function tests were
      found to be normal. Liver function tests were deranged with Gamma GT 244 u/l
      (twice normal). An abdominal Ultrasound Scan suggested a possible splenic
      infarction, which was confirmed by a CT scan of her abdomen. Tests were carried
      out to investigate the possibility of a post thrombotic state. Coagulation risk
      factors for thrombosis were within the normal limits; Protein S 67 %(60-140),
      Protein C 103 % (72-146), Antithrombin 3 110 %(80-120) and Activated P C
      Resistance was 1.9(2.0-4.3). The Hams test was negative but the Anticardiolipin
      antibody test was positive. IgM level was 52 (normal is up to 10) and IgG was
      18.8 (normal is up to 10). She also had border line APC Sensitivity 1.9 (2 to
      4.3). Kaolin time 49 sec (70-120) Ktmix 64 sec (70-120), thyroid function test
      revealed TSH 0.32 micro/L, fT4 20.2 pmol/L (10-25). Subsequent determination of
      Anticardiolipin antibody was negative. Her symptoms were settled with the use of
      simple analgesia and she was discharged home with long-term anticoagulation
      medication. The INR target for long-term anticoagulation was aimed at >3.
      CONCLUSION: This case presented to us as an acute abdominal pain. Subsequent
      investigations revealed the presence of splenic infarction. Coagulation risk
      factors for thrombosis proved negative. Haematological investigations revealed
      the presence of anticardiolipin antibodies at the first instance but subsequent
      determinations were negative. Hence, it mimicked Hughes syndrome initially but
      the criteria for temporal persistence of anticardiolipin antibody was not
      fulfilled. Unusual surgical presentation of a thrombotic abnormality as abdominal
      pain due to splenic infarction.

PMID- 16603068
TI  - CED: a conformational epitope database.
AB  - BACKGROUND: Antigen epitopes provide valuable information useful for disease
      prevention, diagnosis, and treatment. Recently, more and more databases focusing
      on different types of epitopes have become available. Conformational epitopes are
      an important form of epitope formed by residues that are sequentially
      discontinuous but close together in three-dimensional space. These epitopes have
      implicit structural information, making them attractive for both theoretical and
      applied biomedical research. However, most existing databases focus on linear
      rather than conformational epitopes. DESCRIPTION: We describe CED, a special
      database of well defined conformational epitopes. CED provides a collection of
      conformational epitopes and related information including the residue make up and
      location of the epitope, the immunological property of the epitope, the source
      antigen and corresponding antibody of the epitope. All entries in this database
      are manually curated from articles published in peer review journals. The
      database can be browsed or searched through a user-friendly web interface. Most
      epitopes in CED can also be viewed interactively in the context of their 3D
      structures. In addition, the entries are also hyperlinked to various databases
      such as Swiss-Prot, PDB, KEGG and PubMed, providing wide background information.
      CONCLUSION: A conformational epitope database called CED has been developed as an
      information resource for investigators involved in both theoretical and applied
      immunology research. It complements other existing specialised epitope databases.
      The database is freely available at http://web.kuicr.kyoto-u.ac.jp/~ced.

PMID- 16603069
TI  - Analysis of tag-position bias in MPSS technology.
AB  - BACKGROUND: Massively Parallel Signature Sequencing (MPSS) technology was
      recently developed as a high-throughput technology for measuring the
      concentration of mRNA transcripts in a sample. It has previously been observed
      that the position of the signature tag in a transcript (distance from 3' end) can
      affect the measurement, but this effect has not been studied in detail. RESULTS:
      We quantify the effect of tag-position bias in Classic and Signature MPSS
      technology using published data from Arabidopsis, rice and human. We investigate
      the relationship between measured concentration and tag-position using nonlinear
      regression methods. The observed relationship is shown to be broadly consistent
      across different data sets. We find that there exist different and significant
      biases in both Classic and Signature MPSS data. For Classic MPSS data, genes with
      tag-position in the middle-range have highest measured abundance on average while
      genes with tag-position in the high-range, far from the 3' end, show a
      significant decrease. For Signature MPSS data, high-range tag-position genes tend
      to have a flatter relationship between tag-position and measured abundance. Thus,
      our results confirm that the Signature MPSS method fixes a substantial problem
      with the Classic MPSS method. For both Classic and Signature MPSS data there is a
      positive correlation between measured abundance and tag-position for low-range
      tag-position genes. Compared with the effects of mRNA length and number of exons,
      tag-position bias seems to be more significant in Arabadopsis. The tag-position
      bias is reflected both in the measured abundance of genes with a significant tag
      count and in the proportion of unexpressed genes identified. CONCLUSION: Tag
      position bias should be taken into consideration when measuring mRNA transcript
      abundance using MPSS technology, both in Classic and Signature MPSS methods.

PMID- 16603070
TI  - What influences recruitment to randomised controlled trials? A review of trials
      funded by two UK funding agencies.
AB  - BACKGROUND: A commonly reported problem with the conduct of multicentre
      randomised controlled trials (RCTs) is that recruitment is often slower or more
      difficult than expected, with many trials failing to reach their planned sample
      size within the timescale and funding originally envisaged. The aim of this study
      was to explore factors that may have been associated with good and poor
      recruitment in a cohort of multicentre trials funded by two public bodies: the UK
      Medical Research Council (MRC) and the Health Technology Assessment (HTA)
      Programme. METHODS: The cohort of trials was identified from the administrative
      databases held by the two funding bodies. 114 trials that recruited participants
      between 1994 and 2002 met the inclusion criteria. The full scientific
      applications and subsequent trial reports submitted by the trial teams to the
      funders provided the principal data sources. Associations between trial
      characteristics and recruitment success were tested using the Chi-squared test,
      or Fisher's exact test where appropriate. RESULTS: Less than a third (31%) of the
      trials achieved their original recruitment target and half (53%) were awarded an
      extension. The proportion achieving targets did not appear to improve over time.
      The overall start to recruitment was delayed in 47 (41%) trials and early
      recruitment problems were identified in 77 (63%) trials. The inter-relationship
      between trial features and recruitment success was complex. A variety of
      strategies were employed to try to increase recruitment, but their success could
      not be assessed. CONCLUSION: Recruitment problems are complex and challenging.
      Many of the trials in the cohort experienced recruitment difficulties. Trials
      often required extended recruitment periods (sometimes supported by additional
      funds). While this is of continuing concern, success in addressing the trial
      question may be more important than recruitment alone.

PMID- 16603071
TI  - Antibiotic resistance as a global threat: evidence from China, Kuwait and the
      United States.
AB  - BACKGROUND: Antimicrobial resistance is an under-appreciated threat to public
      health in nations around the globe. With globalization booming, it is important
      to understand international patterns of resistance. If countries already
      experience similar patterns of resistance, it may be too late to worry about
      international spread. If large countries or groups of countries that are likely
      to leap ahead in their integration with the rest of the world--China being the
      standout case--have high and distinctive patterns of resistance, then a
      coordinated response could substantially help to control the spread of
      resistance. The literature to date provides only limited evidence on these
      issues. METHODS: We study the recent patterns of antibiotic resistance in three
      geographically separated, and culturally and economically distinct countries-
      China, Kuwait and the United States--to gauge the range and depth of this global
      health threat, and its potential for growth as globalization expands. Our primary
      measures are the prevalence of resistance of specific bacteria to specific
      antibiotics. We also propose and illustrate methods for aggregating specific "bug
      drug" data. We use these aggregate measures to summarize the resistance pattern
      for each country and to study the extent of correlation between countries'
      patterns of drug resistance. RESULTS: We find that China has the highest level of
      antibiotic resistance, followed by Kuwait and the U.S. In a study of resistance
      patterns of several most common bacteria in China in 1999 and 2001, the mean
      prevalence of resistance among hospital-acquired infections was as high as 41%
      (with a range from 23% to 77%) and that among community- acquired infections was
      26% (with a range from 15% to 39%). China also has the most rapid growth rate of
      resistance (22% average growth in a study spanning 1994 to 2000). Kuwait is
      second (17% average growth in a period from 1999 to 2003), and the U.S. the
      lowest (6% from 1999 to 2002). Patterns of resistance across the three countries
      are not highly correlated; the most correlated were China and Kuwait, followed by
      Kuwait and the U.S., and the least correlated pair was China and the U.S.
      CONCLUSION: Antimicrobial resistance is a serious and growing problem in all
      three countries. To date, there is not strong international convergence in the
      countries' resistance patterns. This finding may change with the greater
      international travel that will accompany globalization. Future research on the
      determinants of drug resistance patterns, and their international convergence or
      divergence, should be a priority.

PMID- 16603072
TI  - An unusual cause of alveolar hemorrhage post hematopoietic stem cell
      transplantation: a case report.
AB  - BACKGROUND: Hematopoietic stem cell transplantation is being increasingly used in
      cancer therapy. Diffuse alveolar hemorrhage, an early complication of stem cell
      transplant, results from bacterial, viral and fungal infections, coagulopathy,
      and engraftment syndrome, or can be idiopathic. Diffuse alveolar hemorrhage
      associated with Strongyloides stercoralis hyperinfection in stem cell transplant
      patients has been rarely reported. CASE PRESENTATION: We describe an unusual
      cause of alveolar hemorrhage post hematopoietic stem cell transplant due to
      Strongyloides hyperinfection. Therapy with parenteral ivermectin and
      thiabendazole was initiated but the patient deteriorated and died of respiratory
      failure and septic shock. CONCLUSION: Strongyloides stercoralis hyperinfection is
      an unusual cause of alveolar hemorrhage early after hematopoietic stem cell
      transplant with very high mortality.

PMID- 16603073
TI  - Cytokines, GM-CSF and IFNgamma administered by priming and post-chemotherapy
      cycling in recurrent ovarian cancer patients receiving carboplatin.
AB  - BACKGROUND: Monocyte/macrophages (MO/MA), a polymorphic population of innate
      immune cells, have the potential to mediate antitumor effects, and may also
      contribute to protumor effects. A priming and post-chemotherapy schedule of the
      myeloid cell mobilizing and immune stimulatory growth factor, granulocyte
      monocyte stimulating factor (GM-CSF, Leukine) and the MO/MA activating cytokine
      recombinant interferon gamma 1b (rIFN-gamma1b, Actimmune) has been developed. The
      pre- and post-chemotherapy design is based upon known in vivo kinetics and immune
      modulatory effects of these molecules. Carboplatin (Paraplatin) was selected as
      the cornerstone of treatment of epithelial ovarian cancer (EOC). METHODS: We
      studied hematopoietic and immunologic effects of GM-CSF and rIFN-gamma1b before
      and after carboplatin in patients with recurrent EOC. Potentially chemotherapy
      sensitive patients with recurrent measurable tumors received subcutaneous GM-CSF
      (starting at 400 mug/day) for 7 days plus subcutaneous rIFN-gamma1b (100 mug) on
      days 5 and 7, before and after intravenous carboplatin (area under the curve of
      5). We performed standard hematologic assessment and monitored monocyte (MO),
      dendritic cell, major cell subset counts, and antibody-dependent cell-mediated
      cytotoxicity (ADCC) against a Her2neu+ tumor cell line, as well as selected
      plasma inflammatory cytokine, chemokine and growth factor levels. RESULTS: Our
      analysis comprised only the first 3 months of treatment in the initial 25
      patients. Relative to pretreatment baseline values, white blood cell, neutrophil,
      MO, and eosinophil counts increased (P <or= .001 for each); the proportion of
      platelets increased 9 days after the second (P <or= .002) and third (P <or= .04)
      carboplatin treatments; and the number of cells in the activated MO subsets
      CD14+HLA-DR+, CD14+CD64+, and CD14+CXCR3+ increased (P <or= .04 for each); plasma
      levels of the proangiogenic interleukins 1alpha, 6, and 8 were lower (P <or= .03
      for each); M-CSF, a product of activated MO/MA, was increased on day 9 (P =
      .007); and GM-CSF was increased in plasma after GM-CSF administration (P <or=
      .04). Quality of life measurements were reduced during the GM-CSF/IFN-gamma1b
      cycle while recovering at pre-chemotherapy baseline for FACT-G scores only.
      CONCLUSION: A novel regimen of GM-CSF plus IFN-gamma1b administered to 25 EOC
      patients receiving carboplatin increased myeloid cells, platelets and total
      activated MO populations during the initial 3 months; however, ADCC responses
      were not consistently enhanced during this period.

PMID- 16603074
TI  - Exhaled breath condensate cysteinyl leukotrienes and airway remodeling in
      childhood asthma: a pilot study.
AB  - BACKGROUND: It has been suggested that cysteinyl leukotrienes (cysLTs) play an
      important role in airway remodeling. Previous reports have indicated that cysLTs
      augment human airway smooth muscle cell proliferation. Recently, cysLTs have been
      measured in exhaled breath condensate (EBC). The aim of this study was to
      evaluate the relationship between cysLTs in EBC and another marker of airway
      remodeling, reticular basement membrane (RBM) thickening, in endobronchial
      biopsies in children. METHODS: 29 children, aged 4-15 years, with moderate to
      severe persistent asthma, who underwent bronchoscopy as part of their clinical
      assessment, were included. Subjects underwent spirometry and EBC collection for
      cysLTs analysis, followed by bronchoscopy and endobronchial biopsy within 24
      hours. RESULTS: EBC cysLTs were significantly lower in asthmatic children who
      were treated with montelukast than in those who were not (median (interquartile
      range) 36.62 (22.60-101.05) versus 249.1 (74.21-526.36) pg/ml, p = 0.004). There
      was a significant relationship between EBC cysLTs and RBM thickness in the
      subgroup of children who were not treated with montelukast (n = 13, r = 0.75, p =
      0.003). CONCLUSION: EBC cysLTs appear to be associated with RBM thickening in
      asthma.

PMID- 16603075
TI  - A database and tool, IM Browser, for exploring and integrating emerging gene and
      protein interaction data for Drosophila.
AB  - BACKGROUND: Biological processes are mediated by networks of interacting genes
      and proteins. Efforts to map and understand these networks are resulting in the
      proliferation of interaction data derived from both experimental and
      computational techniques for a number of organisms. The volume of this data
      combined with the variety of specific forms it can take has created a need for
      comprehensive databases that include all of the available data sets, and for
      exploration tools to facilitate data integration and analysis. One powerful
      paradigm for the navigation and analysis of interaction data is an interaction
      graph or map that represents proteins or genes as nodes linked by interactions.
      Several programs have been developed for graphical representation and analysis of
      interaction data, yet there remains a need for alternative programs that can
      provide casual users with rapid easy access to many existing and emerging data
      sets. DESCRIPTION: Here we describe a comprehensive database of Drosophila gene
      and protein interactions collected from a variety of sources, including low and
      high throughput screens, genetic interactions, and computational predictions. We
      also present a program for exploring multiple interaction data sets and for
      combining data from different sources. The program, referred to as the
      Interaction Map (IM) Browser, is a web-based application for searching and
      visualizing interaction data stored in a relational database system. Use of the
      application requires no downloads and minimal user configuration or training,
      thereby enabling rapid initial access to interaction data. IM Browser was
      designed to readily accommodate and integrate new types of interaction data as it
      becomes available. Moreover, all information associated with interaction
      measurements or predictions and the genes or proteins involved are accessible to
      the user. This allows combined searches and analyses based on either common or
      technique-specific attributes. The data can be visualized as an editable graph
      and all or part of the data can be downloaded for further analysis with other
      tools for specific applications. The database is available at
      http://proteome.wayne.edu/PIMdb.html CONCLUSION: The Drosophila Interactions
      Database described here places a variety of disparate data into one easily
      accessible location. The database has a simple structure that maintains all
      relevant information about how each interaction was determined. The IM Browser
      provides easy, complete access to this database and could readily be used to
      publish other sets of interaction data. By providing access to all of the
      available information from a variety of data types, the program will also
      facilitate advanced computational analyses.

PMID- 16603076
TI  - A statistical method for predicting splice variants between two groups of samples
      using GeneChip expression array data.
AB  - BACKGROUND: Alternative splicing of pre-messenger RNA results in RNA variants
      with combinations of selected exons. It is one of the essential biological
      functions and regulatory components in higher eukaryotic cells. Some of these
      variants are detectable with the Affymetrix GeneChip that uses multiple
      oligonucleotide probes (i.e. probe set), since the target sequences for the
      multiple probes are adjacent within each gene. Hybridization intensity from a
      probe correlates with abundance of the corresponding transcript. Although the
      multiple-probe feature in the current GeneChip was designed to assess expression
      values of individual genes, it also measures transcriptional abundance for a sub
      region of a gene sequence. This additional capacity motivated us to develop a
      method to predict alternative splicing, taking advance of extensive repositories
      of GeneChip gene expression array data. RESULTS: We developed a two-step approach
      to predict alternative splicing from GeneChip data. First, we clustered the
      probes from a probe set into pseudo-exons based on similarity of probe
      intensities and physical adjacency. A pseudo-exon is defined as a sequence in the
      gene within which multiple probes have comparable probe intensity values. Second,
      for each pseudo-exon, we assessed the statistical significance of the difference
      in probe intensity between two groups of samples. Differentially expressed pseudo
      exons are predicted to be alternatively spliced. We applied our method to
      empirical data generated from GeneChip Hu6800 arrays, which include 7129 probe
      sets and twenty probes per probe set. The dataset consists of sixty-nine
      medulloblastoma (27 metastatic and 42 non-metastatic) samples and four cerebellum
      samples as normal controls. We predicted that 577 genes would be alternatively
      spliced when we compared normal cerebellum samples to medulloblastomas, and
      predicted that thirteen genes would be alternatively spliced when we compared
      metastatic medulloblastomas to non-metastatic ones. We checked the consistency of
      some of our findings with information in UCSC Human Genome Browser. CONCLUSION:
      The two-step approach described in this paper is capable of predicting some
      alternative splicing from multiple oligonucleotide-based gene expression array
      data with GeneChip technology. Our method employs the extensive repositories of
      gene expression array data available and generates alternative splicing
      hypotheses, which can be further validated by experimental studies.

PMID- 16603077
TI  - Variation at APOE and STH loci and Alzheimer's disease.
AB  - BACKGROUND: The apolipoprotein E (APOE) and tau proteins play important roles in
      the pathological development of Alzheimer's disease (AD). Many studies have shown
      an association between the APOE gene and AD. Association between AD and the newly
      discovered saitohin (STH) gene, nested within the intron of the tau gene, has
      been reported. The present study aimed to elucidate the association between APOE
      and AD, and between STH and AD in our sample. METHODS: The functional
      polymorphisms, rs429358 and rs7412, in the APOE gene (which together define the
      epsilon2, epsilon3, and epsilon4 alleles), and the Q7R SNP in the STH gene, were
      genotyped in 369 patients with AD and 289 healthy European-Americans. The
      associations between these two genes and AD were analyzed in a case-control
      design. RESULTS: Consistent with previously reported results, the frequencies of
      the APOE epsilon4 allele, epsilon4/epsilon4 genotype and epsilon3/epsilon4
      genotype were significantly higher in AD cases than controls; the
      epsilon4/epsilon4 genotype frequency was significantly higher in early-onset AD
      (EOAD) than late-onset AD (LOAD); the frequencies of the epsilon2 allele,
      epsilon3 allele, epsilon3/epsilon3 genotype and epsilon2/epsilon3 genotype were
      significantly lower in AD cases than controls. Positive likelihood ratios (LRs+)
      of APOE alleles and genotypes increased in a linear trend with the number of
      epsilon4 alleles and decreased in a linear trend with the number of epsilon2 or
      epsilon3 alleles. There was no significant difference in the STH allele and
      genotype frequency distributions between AD cases and controls. CONCLUSION: This
      study confirmed that the epsilon4 allele is a dose-response risk factor for AD
      and the epsilon4/epsilon4 genotype was associated with a significantly earlier
      age of onset. Moreover, we found that the epsilon2 allele was a dose-response
      protective factor for AD and the epsilon3 allele exerted a weaker dose-response
      protective effect for risk of AD compared with epsilon2. In a clinical setting,
      APOE genotyping could offer additional biological evidence of whether a subject
      may develop AD, but it is not robust enough to serve as an independent screening
      or predictive test in the diagnosis of AD. STH variation was not significantly
      associated with AD in our sample.

PMID- 16603078
TI  - Active Stat3 is required for survival of human squamous cell carcinoma cells in
      serum-free conditions.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) of the skin is the most aggressive form
      of non-melanoma skin cancer (NMSC), and is the single most commonly diagnosed
      cancer in the U.S., with over one million new cases reported each year. Recent
      studies have revealed an oncogenic role of activated signal transducer and
      activator of transcription 3 (Stat3) in many human tumors, especially in those of
      epithelial origin, including skin SCC. Stat3 is a mediator of numerous growth
      factor and cytokine signaling pathways, all of which activate it through
      phosphorylation of tyrosine 705. RESULTS: To further address the role of Stat3 in
      skin SCC tumorigenesis, we have analyzed a panel of human skin-derived cell lines
      ranging from normal human epidermal keratinocytes (NHEK), to non-tumorigenic
      transformed skin cells (HaCaT), to highly tumorigenic cells (SRB1-m7 and SRB12
      p9) and observed a positive correlation between Stat3 phosphorylation and SCC
      malignancy. We next determined the role of Stat3 activity in cell proliferation
      and viability under serum-free culture conditions. This was accomplished by
      suppressing Stat3 activity in the SRB12-p9 cells through stable expression of a
      dominant negative acting form of Stat3beta, which contains a tyrosine 705 to
      phenylalanine mutation (S3DN). The S3DN cells behaved similar to parental SRB12
      p9 cells when cultured in optimal growth conditions, in the presence of 10% fetal
      calf serum. However, unlike the SRB12-p9 cells, S3DN cells underwent apoptotic
      cell death when cultured in serum-free medium (SFM). This was evidenced by
      multiple criteria, including accumulation of sub-G1 particles, induced PARP
      cleavage, and acquisition of the characteristic morphological changes associated
      with apoptosis. CONCLUSION: This study provides direct evidence for a role for
      Stat3 in maintaining cell survival in the conditions of exogenous growth factor
      deprivation produced by culture in SFM. We also propose that delivery of the S3DN
      gene or protein to tumor cells could induce apoptosis and/or sensitize those
      cells to the apoptotic effects of cancer therapeutic agents, raising the
      possibility of using S3DN as an adjunct for treatment of skin SCC.

PMID- 16603079
TI  - Apolipoprotein E-specific innate immune response in astrocytes from targeted
      replacement mice.
AB  - BACKGROUND: Inheritance of the three different alleles of the human
      apolipoprotein (apo) E gene (APOE) are associated with varying risk or clinical
      outcome from a variety of neurologic diseases. ApoE isoform-specific modulation
      of several pathogenic processes, in addition to amyloid beta metabolism in
      Alzheimer's disease, have been proposed: one of these is innate immune response
      by glia. Previously we have shown that primary microglia cultures from targeted
      replacement (TR) APOE mice have apoE isoform-dependent innate immune activation
      and paracrine damage to neurons that is greatest with TR by the epsilon4 allele
      (TR APOE4) and that derives from p38 mitogen-activated protein kinase (p38MAPK)
      activity. METHODS: Primary cultures of TR APOE2, TR APOE3 and TR APOE4 astrocytes
      were stimulated with lipopolysaccharide (LPS). ApoE secretion, cytokine
      production, and nuclear factor-kappa B (NF-kappaB) subunit activity were measured
      and compared. RESULTS: Here we showed that activation of primary astrocytes from
      TR APOE mice with LPS led to TR APOE-dependent differences in cytokine secretion
      that were greatest in TR APOE2 and that were associated with differences in NF
      kappaB subunit activity. CONCLUSION: Our results suggest that LPS activation of
      innate immune response in TR APOE glia results in opposing outcomes from
      microglia and astrocytes as a result of TR APOE-dependent activation of p38MAPK
      or NF-kappaB signaling in these two cell types.

PMID- 16603080
TI  - Ethnotaxonomy of mastofauna as practised by hunters of the municipality of
      Paulista, state of Paraiba-Brazil.
AB  - It was aimed in the present work to report aspects related to identification,
      naming and categorization of the mastofauna species of the caatinga biome,
      according to hunters' knowledge of Northeast Brazil. The methods of free and semi
      structured interviews and guided tours were applied here. The data obtained were
      analyzed under the emic/etic point of view by comparing the local people's
      knowledge to those reported in the literature. The inland hunters use some
      classification models of mammals living around them as for example the folk
      taxonomy, and a categorization based on the animal utility. Some species are
      preferably hunted for providing food while others are hunted for therapeutic
      ends. Hunt techniques were made evident by the informers. The retrieval and
      comprehension of the whole process related to such knowledge is very important to
      evaluate the human culture and the protection that people exert on local
      biodiversity, since these aspects have implications for the conservation and
      management of faunistic resources.

PMID- 16603081
TI  - Anemia is an independent risk for mortality after acute myocardial infarction in
      patients with and without diabetes.
AB  - INTRODUCTION: Anemia and diabetes are risk factors for short-term mortality
      following an acute myocardial infarction(AMI). Anemia is more prevalent in
      patients with diabetes. We performed a retrospective study to assess the impact
      of the combination of diabetes and anemia on post-myocardial infarction outcomes.
      METHODS: Data relating to all consecutive patients hospitalized with AMI was
      obtained from a population-based disease-specific registry. Patients were divided
      into 4 groups: diabetes and anemia (group A, n = 716), diabetes and no anemia
      (group B, n = 1894), no diabetes and anemia (group C, n = 869), and no diabetes
      and no anemia (group D, n = 3987). Mortality at 30 days and 31 days to 36 months
      were the main outcome measures. RESULTS: 30-day mortality was 32.3% in group A,
      16.1% in group B, 21.5% in group C, 6.6% in group D (all p < 0.001). 31-day to 36
      month mortality was 47.6% in group A, 20.8% in group B, 34.3% in group C, and
      10.4% in group D (all p < 0.001). Diabetes and anemia remained independent risk
      factors for mortality with odds ratios of 1.61 (1.41-1.85, p < 0.001) and 1.59
      (1.38-1.85, p < 0.001) respectively at 36 months. Cardiovascular death from 31
      days to 36-months was 43.7% of deaths in group A, 54.1% in group B, 47.0% in
      group C, 50.8% group D (A vs B, p < 0.05). INTERPRETATION: Patients with both
      diabetes and anemia have a significantly higher mortality than those with either
      diabetes or anemia alone. Cardiovascular death remained the most likely cause of
      mortality in all groups.

PMID- 16603082
TI  - Local knowledge in community-based approaches to medicinal plant conservation:
      lessons from India.
AB  - BACKGROUND: Community-based approaches to conservation of natural resources, in
      particular medicinal plants, have attracted attention of governments, non
      governmental organizations and international funding agencies. This paper
      highlights the community-based approaches used by an Indian NGO, the Rural
      Communes Medicinal Plant Conservation Centre (RCMPCC). The RCMPCC recognized and
      legitimized the role of local medicinal knowledge along with other knowledge
      systems to a wider audience, i.e. higher levels of government. METHODS: Besides a
      review of relevant literature, the research used a variety of qualitative
      techniques, such as semi-structured, in-depth interviews and participant
      observations in one of the project sites of RCMPCC. RESULTS: The review of local
      medicinal plant knowledge systems reveals that even though medicinal plants and
      associated knowledge systems (particularly local knowledge) are gaining wider
      recognition at the global level, the efforts to recognize and promote the un
      codified folk systems of medicinal knowledge are still inadequate. In country
      like India, such neglect is evident through the lack of legal recognition and
      supporting policies. On the other hand, community-based approaches like local
      healers' workshops or village biologist programs implemented by RCMPCC are useful
      in combining both local (folk and codified) and formal systems of medicine.
      CONCLUSION: Despite the high reliance on the local medicinal knowledge systems
      for health needs in India, the formal policies and national support structures
      are inadequate for traditional systems of medicine and almost absent for folk
      medicine. On the other hand, NGOs like the RCMPCC have demonstrated that
      community-based and local approaches such as local healer's workshops and village
      biologist program can synergistically forge linkages between local knowledge with
      the formal sciences (in this case botany and ecology) and generate positive
      impacts at various levels.

PMID- 16603083
TI  - A case study in pathway knowledgebase verification.
AB  - BACKGROUND: Biological databases and pathway knowledge-bases are proliferating
      rapidly. We are developing software tools for computer-aided hypothesis design
      and evaluation, and we would like our tools to take advantage of the information
      stored in these repositories. But before we can reliably use a pathway knowledge
      base as a data source, we need to proofread it to ensure that it can fully
      support computer-aided information integration and inference. RESULTS: We design
      a series of logical tests to detect potential problems we might encounter using a
      particular knowledge-base, the Reactome database, with a particular computer
      aided hypothesis evaluation tool, HyBrow. We develop an explicit formal language
      from the language implicit in the Reactome data format and specify a logic to
      evaluate models expressed using this language. We use the formalism of finite
      model theory in this work. We then use this logic to formulate tests for
      desirable properties (such as completeness, consistency, and well-formedness) for
      pathways stored in Reactome. We apply these tests to the publicly available
      Reactome releases (releases 10 through 14) and compare the results, which
      highlight Reactome's steady improvement in terms of decreasing inconsistencies.
      We also investigate and discuss Reactome's potential for supporting computer
      aided inference tools. CONCLUSION: The case study described in this work
      demonstrates that it is possible to use our model theory based approach to
      identify problems one might encounter using a knowledge-base to support
      hypothesis evaluation tools. The methodology we use is general and is in no way
      restricted to the specific knowledge-base employed in this case study. Future
      application of this methodology will enable us to compare pathway resources with
      respect to the generic properties such resources will need to possess if they are
      to support automated reasoning.

PMID- 16603084
TI  - A novel method to identify and characterise peptide mimotopes of heat shock
      protein 70-associated antigens.
AB  - The heat shock protein, Hsp70, has been shown to play an important role in tumour
      immunity. Vaccination with Hsp70-peptide complexes (Hsp70-PCs), isolated from
      autologous tumour cells, can induce protective immune responses. We have
      developed a novel method to identify synthetic mimic peptides of Hsp70-PCs and to
      test their ability to activate T-cells. Peptides (referred to as "recognisers")
      that bind to Hsp70-PCs from the human breast carcinoma cell line, MDA-MB-231,
      were identified by bio-panning a random peptide M13 phage display library.
      Synthetic recogniser peptides were subsequently used as bait in a reverse bio
      panning experiment to identify potential Hsp70-PC mimic peptides. The ability of
      the recogniser and mimic peptides to prime human lymphocyte responses against
      tumour cell antigens was tested by stimulating lymphocytes with autologous
      peptide-loaded monocyte-derived dendritic cells (DCs). Priming and subsequent
      stimulation with either the recogniser or mimic peptide resulted in interferon
      gamma (IFN-gamma) secretion by the lymphocytes. Furthermore, DCs loaded with
      Hsp70, Hsp70-PC or the recogniser or the mimic peptide primed the lymphocytes to
      respond to soluble extracts from breast cells. These results highlight the
      potential application of synthetic peptide-mimics of Hsp70-PCs, as modulators of
      the immune response against tumours.

PMID- 16603085
TI  - Inhibition of constitutively active Jak-Stat pathway suppresses cell growth of
      human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell
      leukemia cells.
AB  - BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent for
      adult T-cell leukemia (ATL), induces cytokine-independent proliferation of T
      cells, associated with the acquisition of constitutive activation of Janus
      kinases (Jak) and signal transducers and activators of transcription (Stat)
      proteins. Our purposes in this study were to determine whether activation of Jak
      Stat pathway is responsible for the proliferation and survival of ATL cells, and
      to explore mechanisms by which inhibition of Jak-Stat pathway kills ATL cells.
      RESULTS: Constitutive activation of Stat3 and Stat5 was observed in HTLV-1
      infected T-cell lines and primary ATL cells, but not in HTLV-1-negative T-cell
      lines. Using AG490, a Jak-specific inhibitor, we demonstrated that the activation
      of Stat3 and Stat5 was mediated by the constitutive phosphorylation of Jak
      proteins. AG490 inhibited the growth of HTLV-1-infected T-cell lines and primary
      ATL cells by inducing G1 cell-cycle arrest mediated by altering the expression of
      cyclin D2, Cdk4, p53, p21, Pim-1 and c-Myc, and by apoptosis mediated by the
      reduced expression of c-IAP2, XIAP, survivin and Bcl-2. Importantly, AG490 did
      not inhibit the growth of normal peripheral blood mononuclear cells. CONCLUSION:
      Our results indicate that activation of Jak-Stat pathway is responsible for the
      proliferation and survival of ATL cells. Inhibition of this pathway may provide a
      new approach for the treatment of ATL.

PMID- 16603086
TI  - Expression analysis of mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2) in more
      than 300 human tumors and matching normal tissues reveals their co-expression in
      gynecologic malignancies.
AB  - BACKGROUND: Mammaglobin A (SCGB2A2) and lipophilin B (SCGB1D2), two members of
      the secretoglobin superfamily, are known to be co-expressed in breast cancer,
      where their proteins form a covalent complex. Based on the relatively high tissue
      specific expression pattern, it has been proposed that the mammaglobin A protein
      and/or its complex with lipophilin B could be used in breast cancer diagnosis and
      treatment. In view of these clinical implications, the aim of the present study
      was to analyze the expression of both genes in a large panel of human solid
      tumors (n = 309), corresponding normal tissues (n = 309) and cell lines (n = 11),
      in order to evaluate their tissue specific expression and co-expression pattern.
      METHODS: For gene and protein expression analyses, northern blot, dot blot
      hybridization of matched tumor/normal arrays (cancer profiling arrays),
      quantitative RT-PCR, non-radioisotopic RNA in situ hybridization and
      immunohistochemistry were used. RESULTS: Cancer profiling array data demonstrated
      that mammaglobin A and lipophilin B expression is not restricted to normal and
      malignant breast tissue. Both genes were abundantly expressed in tumors of the
      female genital tract, i.e. endometrial, ovarian and cervical cancer. In these
      four tissues the expression pattern of mammaglobin A and lipophilin B was highly
      concordant, with both genes being down-, up- or not regulated in the same tissue
      samples. In breast tissue, mammaglobin A expression was down-regulated in 49% and
      up-regulated in 12% of breast tumor specimens compared with matching normal
      tissues, while lipophilin B was down-regulated in 59% and up-regulated in 3% of
      cases. In endometrial tissue, expression of mammaglobin A and lipophilin B was
      clearly up-regulated in tumors (47% and 49% respectively). Both genes exhibited
      down-regulation in 22% of endometrial tumors. The only exceptions to this
      concordance of mammaglobin A/lipophilin B expression were normal and malignant
      tissues of prostate and kidney, where only lipophilin B was abundantly expressed
      and mammaglobin A was entirely absent. RNA in situ hybridization and
      immunohistochemistry confirmed expression of mammaglobin A on a cellular level in
      endometrial and cervical cancer and their corresponding normal tissues.
      CONCLUSION: Altogether, these data suggest that expression of mammaglobin A and
      lipophilin B might be controlled in different tissues by the same regulatory
      transcriptional mechanisms. Diagnostic assays based on mammaglobin A expression
      and/or the mammaglobin A/lipophilin B complex appear to be less specific for
      breast cancer, but with a broader spectrum of potential applications, which
      includes gynecologic malignancies.

PMID- 16603087
TI  - A tale of two ferredoxins: sequence similarity and structural differences.
AB  - BACKGROUND: Sequence similarity between proteins is usually considered a reliable
      indicator of homology. Pyruvate-ferredoxin oxidoreductase and quinol-fumarate
      reductase contain ferredoxin domains that bind [Fe-S] clusters and are involved
      in electron transport. Profile-based methods for sequence comparison, such as PSI
      BLAST and HMMer, suggest statistically significant similarity between these
      domains. RESULTS: The sequence similarity between these ferredoxin domains
      resides in the area of the [Fe-S] cluster-binding sites. Although overall folds
      of these ferredoxins bear no obvious similarity, the regions of sequence
      similarity display a remarkable local structural similarity. These short regions
      with pronounced sequence motifs are incorporated in completely different
      structural environments. In pyruvate-ferredoxin oxidoreductase (bacterial
      ferredoxin), the hydrophobic core of the domain is completed by two beta
      hairpins, whereas in quinol-fumarate reductase (alpha-helical ferredoxin), the
      cluster-binding motifs are part of a larger all-alpha-helical globin-like fold
      core. CONCLUSION: Functionally meaningful sequence similarity may sometimes be
      reflected only in local structural similarity, but not in global fold similarity.
      If detected and used naively, such similarities may lead to incorrect fold
      predictions.

PMID- 16603088
TI  - Phylogenetic analyses of Vitis (Vitaceae) based on complete chloroplast genome
      sequences: effects of taxon sampling and phylogenetic methods on resolving
      relationships among rosids.
AB  - BACKGROUND: The Vitaceae (grape) is an economically important family of
      angiosperms whose phylogenetic placement is currently unresolved. Recent
      phylogenetic analyses based on one to several genes have suggested several
      alternative placements of this family, including sister to Caryophyllales,
      asterids, Saxifragales, Dilleniaceae or to rest of rosids, though support for
      these different results has been weak. There has been a recent interest in using
      complete chloroplast genome sequences for resolving phylogenetic relationships
      among angiosperms. These studies have clarified relationships among several major
      lineages but they have also emphasized the importance of taxon sampling and the
      effects of different phylogenetic methods for obtaining accurate phylogenies. We
      sequenced the complete chloroplast genome of Vitis vinifera and used these data
      to assess relationships among 27 angiosperms, including nine taxa of rosids.
      RESULTS: The Vitis vinifera chloroplast genome is 160,928 bp in length, including
      a pair of inverted repeats of 26,358 bp that are separated by small and large
      single copy regions of 19,065 bp and 89,147 bp, respectively. The gene content
      and order of Vitis is identical to many other unrearranged angiosperm chloroplast
      genomes, including tobacco. Phylogenetic analyses using maximum parsimony and
      maximum likelihood were performed on DNA sequences of 61 protein-coding genes for
      two datasets with 28 or 29 taxa, including eight or nine taxa from four of the
      seven currently recognized major clades of rosids. Parsimony and likelihood
      phylogenies of both data sets provide strong support for the placement of
      Vitaceae as sister to the remaining rosids. However, the position of the Myrtales
      and support for the monophyly of the eurosid I clade differs between the two data
      sets and the two methods of analysis. In parsimony analyses, the inclusion of
      Gossypium is necessary to obtain trees that support the monophyly of the eurosid
      I clade. However, maximum likelihood analyses place Cucumis as sister to the
      Myrtales and therefore do not support the monophyly of the eurosid I clade.
      CONCLUSION: Phylogenies based on DNA sequences from complete chloroplast genome
      sequences provide strong support for the position of the Vitaceae as the earliest
      diverging lineage of rosids. Our phylogenetic analyses support recent assertions
      that inadequate taxon sampling and incorrect model specification for concatenated
      multi-gene data sets can mislead phylogenetic inferences when using whole
      chloroplast genomes for phylogeny reconstruction.

PMID- 16603090
TI  - Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC)
      study of aseptic meningitis.
AB  - BACKGROUND: The seasonality, clinical and radiographic features and outcome of
      aseptic meningitis have been described for regional outbreaks but data from a
      wider geographic area is necessary to delineate the epidemiology of this
      condition. METHODS: A retrospective chart review was completed of children
      presenting with aseptic meningitis to eight Canadian pediatric hospitals over a
      two-year period. RESULTS: There were 233 cases of proven enteroviral (EV)
      meningitis, 495 cases of clinical aseptic meningitis and 74 cases of possible
      aseptic meningitis with most cases occurring July to October. Headache, vomiting,
      meningismus and photophobia were more common in children > or = 5 years of age,
      while rash, diarrhea and cough were more common in children < 5 years of age.
      Pleocytosis was absent in 22.3% of children < 30 days of age with proven EV
      meningitis. Enterovirus was isolated in cerebrospinal fluid (CSF) from 154 of 389
      patients (39.6%) who had viral culture performed, and a nucleic acid
      amplification test for enterovirus was positive in CSF from 81 of 149 patients
      (54.3%). Imaging of the head by computerized tomography or magnetic resonance
      imaging was completed in 96 cases (19.7%) and 24 had abnormal findings that were
      possibly related to meningitis while none had changes that were definitely
      related to meningitis. There was minimal morbidity and there were no deaths.
      CONCLUSION: The clinical presentation of aseptic meningitis varies with the age
      of the child. Absence of CSF pleocytosis is common in infants < 30 days of age.
      Enterovirus is the predominant isolate, but no etiologic agent is identified in
      the majority of cases of aseptic meningitis in Canadian children.

PMID- 16603089
TI  - The role of steroids in follicular growth.
AB  - The steroidogenic pathway within the ovary gives rise to progestins, androgens
      and oestrogens, all of which act via specific nuclear receptors to regulate
      reproductive function and maintain fertility. The role of progestins in
      follicular growth and development is limited, its action confined largely to
      ovulation, although direct effects on granulosa cell function have been reported.
      Consistent with these findings, progesterone receptor knockout mice are infertile
      because they cannot ovulate. Androgens have been shown to promote early
      follicular growth, but also to impede follicular development by stimulating
      atresia and apoptosis. The inability of androgens to transduce a signal in mice
      lacking androgen receptors culminates in reduced fertility. Oestrogens are known
      to exert effects on granulosa cell growth and differentiation in association with
      gonadotrophins. Studies with oestrogen receptor knockouts and oestrogen depleted
      mice have shown us that oestrogen is essential for folliculogenesis beyond the
      antral stage and is necessary to maintain the female phenotype of ovarian somatic
      cells. In summary, the action of steroids within the ovary is based on the
      developmental status of the follicle. In the absence of any single sex steroid,
      ovarian function and subsequently fertility, are compromised.

PMID- 16603091
TI  - Surveillance of HIV and syphilis infections among antenatal clinic attendees in
      Tanzania-2003/2004.
AB  - BACKGROUND: This paper presents the prevalence of human immunodeficiency virus
      (HIV) and syphilis infections among women attending antenatal clinics (ANC) in
      Tanzania obtained during the 2003/2004 ANC surveillance. METHODS: Ten
      geographical regions; six of them were involved in a previous survey, while the
      remaining four were freshly selected on the basis of having the largest
      population among the remaining 20 regions. For each region, six ANC were
      selected, two from each of three strata (urban, peri-urban and rural). Three of
      the sites did not participate, resulting into 57 surveyed clinics. 17,813 women
      who were attending the chosen clinics for the first time for any pregnancy
      between October 2003 and January 2004. Patient particulars were obtained by
      interview and blood specimens were drawn for HIV and syphilis testing. HIV
      testing was done anonymously and the results were unlinked. RESULTS: Of the
      17,813 women screened for HIV, 1,545 (8.7% (95% CI = 8.3-9.1)) tested positive
      with the highest prevalence in women aged 25-34 years (11%), being higher among
      single women (9.7%) than married women (8.6%) (p < 0.07), and increased with
      level of education from 5.2% among women with no education to 9.3% among those at
      least primary education (p < 0.001). Prevalence ranged from 4.8% (95% CI = 3.8%
      9.8%) in Kagera to 15.3% (95% CI = 13.9%-16.8%) in Mbeya and was; 3.7%, 4.7%,
      9.1%, 11.2% and 15.3% for rural, semi-urban, road side, urban and 15.3% border
      clinics, respectively (p < 0.001). Of the 17,323 women screened for syphilis,
      1265 (7.3% (95%CI = 6.9-7.7)) were positive, with highest prevalence in the age
      group 35-49 yrs (10.4%) (p < 0.001), and being higher among women with no
      education than those with some education (9.8% versus 6.8%) (p < 0.0001), but
      marital status had no influence. Prevalence ranged from 2.1% (95% CI = 1.4%-3.0%)
      in Kigoma to 14.9% (95% CI = 13.3%-16.6%) in Kagera and was 16.0% (95% CI = 13.3
      18.9), 10.5% (95% CI = 9.5-11.5) and 5.8% (95% CI = 5.4-6.3) for roadside, rural
      and urban clinics, respectively. Syphilis and HIV co-infection was seen in
      130/17813 (0.7%). CONCLUSION: The high HIV prevalence observed among the ANC
      clinic attendees in Tanzania call for expansion of current voluntary counselling
      and testing (VCT) services and access to antiretroviral drugs (ARV) in the
      clinics. There is also a need for modification of obstetric practices and infant
      feeding options in HIV infection in order to prevent mother to child transmission
      of HIV. To increase uptake to HIV testing the opt-out strategy in which all
      clients are offered HIV testing is recommended in order to meet the needs of as
      many pregnant women as possible.

PMID- 16603092
TI  - Microsatellite polymorphism across the M. tuberculosis and M. bovis genomes:
      implications on genome evolution and plasticity.
AB  - BACKGROUND: Microsatellites are the tandem repeats of nucleotide motifs of size 1
      6 bp observed in all known genomes. These repeats show length polymorphism
      characterized by either insertion or deletion (indels) of the repeat units, which
      in and around the coding regions affect transcription and translation of genes.
      RESULTS: Systematic comparison of all the equivalent microsatellites in the
      coding regions of the three mycobacterial genomes, viz. Mycobacterium
      tuberculosis H37Rv, Mycobacterium tuberculosis CDC1551 and Mycobacterium bovis,
      revealed for the first time the presence of several polymorphic microsatellites.
      The coding regions affected by frame-shifts owing to microsatellite indels have
      undergone changes indicative of gene fission/fusion, premature termination and
      length variation. Interestingly, the genes affected by frame-shift mutations code
      for membrane proteins, transporters, PPE, PE_PGRS, cell-wall synthesis proteins
      and hypothetical proteins. CONCLUSION: This study has revealed the role of
      microsatellite indel mutations in imparting novel functions and a certain degree
      of plasticity to the mycobacterial genomes. There seems to be some correlation
      between microsatellite polymorphism and the variations in virulence, host
      pathogen interactions mediated by surface antigen variations, and adaptation of
      the pathogens. Several of the polymorphic microsatellites reported in this study
      can be tested for their polymorphic nature by screening clinical isolates and
      various mycobacterial strains, for establishing correlations between
      microsatellite polymorphism and the phenotypic variations among these pathogens.

PMID- 16603093
TI  - Deletions in the Y-derived amelogenin gene fragment in the Indian population.
AB  - BACKGROUND: Rare failures in amelogenin-based gender typing of individuals have
      been observed globally. In this study, we report the deletion of a large fragment
      of the amelogenin gene in 10 individuals out of 4,257 male samples analyzed from
      104 different endogamous populations of India. METHODS: Samples were analyzed
      using commercial genetic profiling kits. Those that exhibited failures in
      amelogenin-based gender identification were further analyzed with published as
      well as newly designed primers to ascertain the nature and extent of mutation.
      RESULTS: The failure rate among Indian males was 0.23 %. Though the exact size
      and nature of the deletion (single point mutations at a number of positions or a
      single large deletion) could not be determined in the present study, it is
      inferred that the deletion spans a region downstream of the reverse primer
      binding site of commercially available amelogenin primer sets. Deletions were
      conspicuously absent among the Mongoloid tribes of Northeast India, while both
      caste and tribal groups harbored these mutations, which was predominantly among
      the Y-chromosomes belonging to J2 lineage. CONCLUSION: Our study indicates that
      the different amelogenin primer sets currently included in genetic profiling
      multiplex kits may result in erroneous interpretations due to mutations
      undetectable during routine testing. Further there are indications that these
      mutations could possibly be lineage-specific, inherited deletions.

PMID- 16603094
TI  - Administration of bisphosphonate for hypercalcemia associated with oral cancer.
AB  - BACKGROUND: The efficacy of treating hypercalcemia with bisphosphonate (BP) in
      patients with advanced oral cancer has not been fully investigated. This
      retrospective study evaluated the clinical course of hypercalcemic patients with
      and without BP treatment. METHODS: Sixteen hypercalcemic patients, most of whom
      had uncontrollable locoregional lesions and lung metastases, were studied. Nine
      patients had been given BP, and the rest had not. RESULTS: There were significant
      differences in age and serum ALT between the BP-treated and -untreated groups.
      The first administration of BP effectively and safely decreased the serum calcium
      level, but repeated administrations were less effective. Although the patients
      treated with BP survived significantly longer than the untreated subjects, the
      difference of the median was only about 2 weeks. CONCLUSION: The occurrence of
      hypercalcemia in oral cancer patients apparently implies an extremely poor
      prognosis, and long-term survival cannot be expected, even with BP treatment.

PMID- 16603095
TI  - The role of adhesion molecules in atopic dermatitis.
AB  - Adhesion molecules may play an important role in the homing of T-cell subsets
      into allergen-exposed skin of atopic individuals. The aim of this pilot study was
      to examine the expression of adhesion molecules in atopic dermatitis (AD) skin
      lesions. Biopsies were taken at acute skin lesions from 10 AD patients and 5
      healthy controls, and were studied by immunohistocytochemistry for the expression
      of E-selectin, L-selectin, ICAM-1 and ICAM-3 on cells in the epidermis and
      dermis. Study results revealed all AD patients to express ICAM-1 (10/10) and ICAM
      3 (10/10) in the dermis, and most of them to express E-selectin (9/10) and L
      selectin (6/10) in the dermis, without expression of E- and L-selectins in the
      epidermis. Our results revealed a high expression of adhesion molecules,
      especially ICAM-1 and ICAM-3, in the skin lesions of AD patients, which may play
      an important role in the pathogenesis of AD, and these preliminary results may be
      of clinical relevance for the treatment of AD.

PMID- 16603096
TI  - Immunological parameters in the sera of patients with atopic dermatitis and
      airborne allergy treated with allergy vaccines.
AB  - Patients with atopic disorders present an increased production of IgE, which is
      usually limited to specific antibodies against various environmental allergens.
      It has also been suggested that the production of these antibodies may be
      influenced by effective specific immunotherapy (SIT). Of course, a decline of
      serum antigen specific IgE in the course of such a treatment cannot explain the
      clinical efficacy of SIT and is probably not a key mechanism. However, SIT may at
      least participate in the final clinical result. In this study, 37 patients with
      atopic dermatitis were treated with allergy vaccines (Novo-Helisen Depot) for a
      time period of 48 months. The control group consisted of 29 patients with atopic
      dermatitis who were treated with classical methods. The clinical score (W-AZS),
      total IgE and antigen specific IgE (asIgE) in the sera of patients were assessed
      before treatment and after 24 and 48 months of therapy (FEIA CAP System,
      Pharmacia). There was a significant difference between the two investigated
      groups from both the clinical and immunological standpoints after 2 and 4 years
      of observation. There was a significant decrease of serum total IgE and asIgE
      (directed against airborne allergens) in the course of specific immunotherapy. In
      the control group, the total IgE level tended to increase, and this tendency was
      also recorded in case of asIgE measurements. We also evaluated the influence of
      specific immunotherapy on the serum level of IFN-G, sIL-2R, IL-4, IL-5 and IL-10
      before treatment and after 4 years of therapy with the quantitative 2-step
      colorimetric sandwich ELISA method (R and D Systems). In the group of patients
      treated with allergy vaccines, a significant decrease of the serum sIL-2R level
      was observed after 48 months of therapy (p<0.01). In the control group, a
      significant increase of serum IL-4 (p<0.01) as well as IL-5 (p<0.05) was
      registered at the end of the observation period. There was no significant
      correlation between the clinical score and serum level of any of the investigated
      cytokines in either group of patients before the treatment or after 48 months of
      therapy.

PMID- 16603097
TI  - Geomyces pannorum as a possible causative agent of dermatomycosis and
      onychomycosis in two patients.
AB  - Chrysosporium pannorum (Link) Hughes is a soil keratinophilic fungus present in
      organic residues, on human skin surface and in the general environment of human
      beings. Clear evidence for the pathogenicity of this fungus for human beings was
      lacking. In 1999, a case of fungal infection in a chow-chow dog and its owner was
      published, where Chrysosporium pannorum (Link) Hughes was determined as the only
      possible infection trigger. The State Hygiene Institute in Bratislava repeatedly
      confirmed the cultivation results. Chrysosporium pannorum (Link) Hughes was
      detected in the material provided by a ZOO: camel, tiger and antelope hair,
      whereby the same finding as in the dog mentioned above was described, i.e.
      extensive alopecic foci of various size. Since 2000 the cultivations have been
      monitored with due care. Eight positive cultivations of Chrysosporium pannorum
      (Link) Hughes have been detected until now, two of them in patients with a flair
      for horticulture. In a male patient, fingernail onychomycosis with affected skin
      on forearms, hands and fingers was determined. In a female patient only nail
      plates were affected. Chrysosporium pannorum was confirmed to be the only
      possible pathogen. Therapy with itraconazole produced excellent results in both
      patients and no relapses were recorded. Based on our repeated findings it is
      concluded that the evidence for non-pathogenicity of Chrysosporium pannorum
      should be revised.

PMID- 16603098
TI  - The effect of treatment for vaginal yeast infection on the prevalence of
      bacterial vaginosis in early pregnancy.
AB  - Both bacterial vaginosis and candidiasis are commonly seen in pregnancy, with
      marked differences in pregnancy outcome. The aim of this study was to assess the
      effect of antifungal treatment on the prevalence of bacterial vaginosis in early
      pregnancy. This prospective randomized study included 126 women in early
      pregnancy with heavy vaginal yeast colonization and 88 healthy controls. Vaginal
      flora was evaluated on initial visit and on two check-ups for the presence of
      bacterial vaginosis. Half of the heavily colonized patients received an
      antimycotic agent (clotrimazole). The prevalence of vaginosis was compared among
      the three groups. Xi (2)-test and Fisher's exact test were used for statistical
      analysis. Three of 72 (4.2%) yeast-free controls, two of 79 (2.5%) yeast infected
      but not treated patients, and nine of 63 (14.3%) infected and treated patients
      presented with bacterial vaginosis 4 weeks after the initial visit. There was a
      statistically significant increase in the prevalence of bacterial vaginosis
      (p<0.03) in yeast infected and treated patients as compared to colonized and
      untreated patients. Treatment of candidiasis in early pregnancy may contribute to
      an increased rate of bacterial vaginosis.

PMID- 16603099
TI  - Cutaneous manifestations in a patient with a long-term history of untreated ACTH
      dependent Cushing's syndrome.
AB  - Cushing's syndrome is accompanied by many different skin symptoms. A case of a 43
      year-old female patient with unrecognized adrenocorticotropic hormone (ACTH)
      dependent Cushing syndrome is reported. Besides numerous skin lesions, the
      patient presented with a rapidly progressive leg ulcer due to venous thrombosis.
      The initial skin symptoms appeared on her lower leg one month prior to admission.
      The patient was treated with oral prednisone, however, rapid progression of the
      skin lesion was observed. On admission the patient presented with a large, very
      painful ulceration, partially covered with a crust, on the right lower leg with
      several satellite smaller ulcerations. The other leg showed no changes. Moreover,
      the patient had pronounced hirsutism and skin darkening on the face, and
      Muehrcke's lines were observed on all her nails. Microscopic findings of skin
      biopsy were uncharacteristic, with some signs of angiopathy and vasculitis. Based
      on the elevated serum levels of ACTH and cortisol, and the result of
      dexamethasone suppression test, ACTH-dependent Cushing syndrome was diagnosed.
      Sonography of leg veins revealed a recanalized thrombus of the right popliteal
      vein with reflux. The patient was transferred to surgical department where both
      suprarenal glands were removed. Upon suprarenal gland removal, significant
      improvement of the patient's general condition and rapid healing of the leg ulcer
      were observed. Briefly, this patient is presented to point out that a leg ulcer
      caused by venous insufficency may mimic fulminant purpura or some other type of
      vasculitis in patients with Cushing syndrome.

PMID- 16603100
TI  - Pyoderma gangrenosum associated with ulcerative colitis.
AB  - We report the case of a 45-year old man with non-healing ulcers located on his
      chest, lumbal, sacral, retroauricular areas and forehead. Both clinical and
      histopathological examinations suggested pyoderma gangrenosum (PG). For six
      months the diagnosis of ulcerative colitis was established. PG in our patient was
      presented as a rapidly enlarging, painful ulcer with purple, undermined edges and
      a necrotic, haemorrhagic base. Initially, he was treated with a high dosage of
      peroral glucocorticosteroid, sulfasalazine, and systemic antibiotics, together
      with daily wound care. Ulceration partially regressed. Total colonoscopy showed
      pancolitis. When the dose of glucocorticosteroids was tapered down to 35 mg, new
      ulcerations on his right thigh and abdomen were formed. He also developed E. coli
      sepsis and flare up of bowel disease. Azathioprine, together with two pulse doses
      of glucocorticosteroids and antibiotics, were administered. He was scheduled for
      a total colectomy. The management of PG continues to be a therapeutic challenge.

PMID- 16603101
TI  - Stevens-Johnson syndrome as an unusual adverse effect of azithromycin.
AB  - Stevens-Johnson syndrome mostly involves the skin and mucous membranes. The
      diagnosis is made when the characteristic rash appears 1 to 3 weeks after
      exposure to a known stimulus and cannot be explained by some other diagnosis. A
      62-year-old woman was admitted for evaluation of toxo-allergic dermatitis and
      collagenosis. Ten days prior to admission she was taking a course of azithromycin
      for upper respiratory tract infection. After a few days she was feeling better
      but maculopapular, erythematous rash developed over her palms, accompanied by
      fever and chills as well as reddish discoloration around her eyes. Within the
      next few days the rash progressed to the feet. Routine hematologic, biochemical
      and immunologic studies did not confirm the diagnosis of inflammatory rheumatic
      disease. Corticosteroid therapy with methylprednisolone (1 mg/kg) for the
      presumed Stevens-Johnson syndrome was started and her condition improved in
      several days; she became afebrile and her skin lesions gradually disappeared.
      There is only one report, in a child, documenting the association of Stevens
      Johnson syndrome with azithromycin, as in this patient.

PMID- 16603102
TI  - Giant meta-typical carcinoma: an unusual tumor.
AB  - Meta-typical carcinoma (MTC) or basosquamous carcinoma is a remarkable malignancy
      with features of both basal and squamous cell carcinoma. It is typically located
      on the back and face, often with clinical features of basal cell carcinoma but
      tending to be more aggressive with enhanced prospects of lymph node or distant
      metastases. Our report describes a huge neglected MTC of the back of ten-year
      duration, a giant ulcero-vegetative tumor measuring 20 x 25 cm. Histologic
      examination of specimens from the margins and periphery revealed aspects of both
      basal and squamous cell carcinoma, while the ulcerated center showed sclerotic
      tissue without tumor. Radical excision and reconstruction by grafts were
      performed. No metastases were observed after two years. There are many
      controversies surrounding the histologic definition and biologic behavior of MTC,
      including its metastasizing potential. The MTC we describe exhibited benign
      biologic behavior. This may have been related to an intense inflammatory host
      response with elimination of neoplastic tissue and consequent local sclerosis
      evident in the central tumor-free portion. This central tumor regression is to
      our knowledge a unique finding in MTC.

PMID- 16603103
TI  - Specific immunotherapy in atopic dermatitis.
AB  - Despite the existence of various scientific research on the beneficial effect of
      specific immunotherapy with specific airborne allergens in the treatment of
      atopic dermatitis, this method has not been easily accepted, as the methodology
      and the valuation of the studies were heterogeneous. Over the last few years,
      meta-analysis technology has been developed as a useful tool to globally value
      the results of different research trials related to one specific scientific
      problem. When meta-analyses are carried out correctly, they are accepted as the
      most appropriate way to express the results obtained from different studies. Not
      many studies have been published in the case of atopic dermatitis and specific
      immunotherapy. In this paper, we attempt to present and discuss results obtained
      by various authors on this topic, beginning with the publication of Strauss and
      Kligman in 1957. It should be noted that for patients with IgE-mediated airborne
      allergy, especially children, specific immunotherapy as an early treatment in
      cases of atopic dermatitis could have an additionally preventive nature in terms
      of protection against the development of a respiratory atopic problem. Specific
      immunotherapy should therefore be at least considered in the treatment of
      selected cases of atopic dermatitis patients presenting airborne IgE-mediated
      allergy.

PMID- 16603104
TI  - Cosmetic dermatology -- where is it today?

PMID- 16603105
TI  - 2005 centennial year marking the discovery of the spirochete Treponema pallidum.

PMID- 16603106
TI  - Diagnosis and treatment of common fractures in children: femoral shaft fractures
      and supracondylar humeral fractures.
AB  - Femoral shaft fractures and supracondylar elbow fractures are two of the most
      common major pediatric injuries managed by the general orthopedic surgeon.
      Therapeutic choices frequently are influenced by many factors, including
      associated injuries, fracture type, and the child's age, social situation, and
      economic issues. Nonsurgical management of femoral shaft fractures has been a
      preferred and cost-effective treatment for most age groups, but recently the use
      of surgical techniques has gained popularity with the overall goal of rapid
      mobilization of the child. Supracondylar elbow fractures are diagnostically
      challenging and can result in severe acute and long-term complications. An
      understanding of fracture presentation, anatomic detail, and surgical
      applications will optimize the chances for successful outcomes.

PMID- 16603107
TI  - Fate of the normal uninvolved hip opposite closed reduction of unilateral
      developmental dislocation of the hip.
AB  - The purpose of this study was to determine the incidence of avascular necrosis
      and acetabular dysplasia in the normal uninvolved contralateral hip opposite a
      unilateral dislocated hip. Thirty-five children with unilateral developmental
      dislocation of the hip underwent closed reduction. Medical records were reviewed
      for gender, side, age at reduction, and presence of the ossific nucleus at
      reduction. Avascular necrosis was reported as present if there was proximal
      femoral deformity on postoperative radiographs. Acetabular dysplasia was noted as
      present based on reported values. The mean age at reduction was 10 months. The
      mean age at time of follow-up radiograph was 101 months. There was no evidence of
      avascular necrosis in any of the uninvolved hips. Acetabular dysplasia was
      present in 22 (63%) uninvolved hips.

PMID- 16603108
TI  - Vacuum-assisted closure for fasciotomy wounds following compartment syndrome of
      the leg.
AB  - This study evaluated the efficacy of vacuum-assisted closure (VAC) for treatment
      of fasciotomy wounds for traumatic compartment syndrome. The authors reviewed the
      records of a consecutive series of 34 patients who had compartment syndrome of
      the leg requiring the standard two-incision release of all four compartments and
      received the application of VAC therapy until the time of definitive wound
      closure or coverage. A matched series of 34 consecutive antecedent patients with
      the same entry criteria, except for the use of the VAC, were also studied and
      served as a control group. The main parameter of interest was the time to
      "definitive closure" (delayed primary closure with sutures or skin graft
      coverage) of the wounds. Of the 68 wounds in 34 patients managed with VAC, the
      average time to definitive closure for both the lateral and the medial wounds was
      6.7 days. For the 70 wounds in the 34 control patients, the average time to
      definitive closure was 16.1 days. This difference in time to wound closure
      between the VAC group and the non-VAC group was statistically significant (p <
      .05). Subatmospheric treatment for compartment syndrome of the leg after
      fasciotomy theoretically helps to speed the resolution of the swelling and tissue
      edema that are often components of this clinical entity. Experimental work has
      shown vacuum-assisted wound management to be effective in hastening the
      resolution of wound edema, enhancing local blood flow, promoting granulation
      tissue, and thwarting bacterial colonization. These factors may account for its
      utility in the management of fasciotomy wounds in the setting of compartment
      syndrome of the leg.

PMID- 16603109
TI  - A comparison of outcomes of anterior cervical discectomy and fusion in patients
      with and without radicular symptoms.
AB  - Anterior cervical discectomy and fusion (ACDF) is commonly performed for
      degenerative conditions of the cervical spine with good to excellent results.
      There is controversy over the use of ACDF for patients with axial neck pain
      alone. A retrospective review of 202 patients from two private practice
      orthopaedic spine surgeons following ACDF with 39-month mean follow-up was
      performed. Patients completed pain drawings, pre- and postoperative visual analog
      pain scales (VAS), Oswestry functional capacity evaluations (OSW), and a
      postoperative neck disability index. Forty-one patients had axial neck pain
      alone, and 161 had radicular pain with or without neck pain. There were
      significant improvements in VAS and OSW scores following surgery for the combined
      study population as well as the neck pain only and radicular pain groups (p <
      .01). ACDF can be effectively used for treatment of patients with axial neck pain
      without radicular symptoms.

PMID- 16603110
TI  - Muscle transfers involving the shoulder.
AB  - Muscle transfer provides a viable treatment option for several difficult problems
      involving the shoulder. Muscle transfer is often the only alternative to a
      salvage procedure such as shoulder fusion, and whereas salvage procedures provide
      pain relief at the cost of function, muscle transfer can provide pain relief
      while retaining acceptable function. The five most commonly encountered shoulder
      problems for which muscle transfer can be utilized are subscapularis rupture,
      irreparable rotator cuff tear, deltoid injury and dysfunction, trapezial
      paralysis, and serratus anterior scapular winging. Although numerous muscle
      transfer procedures have been described, the following procedures have proven the
      most reliable and are the focus of this article: 1) transfer of the pectoralis
      major for subscapularis rupture, 2) transfer of the latissimus dorsi for
      irreparable rotator cuff tears, 3) latissimus dorsi transfer for deltoid injury
      or dysfunction, 4) modified Eden-Lange procedure for trapezial paralysis, and 5)
      modified Marmor-Bechtol pectoralis major transfer for serratus anterior scapular
      winging.

PMID- 16603111
TI  - Management of odontoid fractures with anterior screw fixation.
AB  - Type II odontoid fractures are prone to undergo nonunion. Stabilization of such
      fractures with anterior screw fixation provides rigid internal fixation and
      preserves C1-C2 motion. During a 5-year period, 17 patients with displaced type
      II fractures of the odontoid were treated Thirteen were male and four were female
      with a mean age of 38.2 years. All patients were operated on for anterior screw
      fixation within a mean of 10.1 days from injury. Postoperatively, the patients
      were evaluated clinically and radiologically at regular intervals. With a mean
      follow-up of 3.2 years, union was observed in 16 of 17 patients (94%). One
      patient developed nonunion for which he required C1-C2 fusion subsequently. Screw
      back-out by a few millimeters was seen in another patient resulting in mild
      restriction of neck movements. No approach-related complications were noted.
      Anterior odontoid screw fixation has relatively low complication and high fusion
      rates. It not only restores normal anatomy but also gives better functional
      results by preserving intrinsic C1-C2 motion. Thus it should be considered the
      treatment of choice in acute displaced type II odontoid fractures.

PMID- 16603112
TI  - Adolescent idiopathic scoliosis: modern management guidelines.
AB  - Adolescent idiopathic scoliosis (AIS), a structural lateral curvature of the
      spine of uncertain etiology, is the most common cause of spinal deformity in
      adolescents. In its most severe form, AIS is characterized by progressive spinal
      curvature that may lead to a permanent deformity. Thus, the goal of treatment is
      early detection and prevention of progression. This article provides a review of
      general spinal anatomy relevant to AIS and its etiology, describes several
      proposed methods of classifying curves in AIS, delineates the natural history of
      AIS, and discusses the nonoperative and operative treatment options.

PMID- 16603113
TI  - Hylan G-F 20 tolerability with repeat treatment in a large orthopedic practice: a
      retrospective review.
AB  - The objective of this study was to determine the incidence of local adverse
      events (AEs) with repeat treatment of hylan G-F 20 for osteoarthritis (OA) knee
      pain relief in the authors' practice. Prospectively collected patient data (5
      year period) was retrospectively reviewed from patients who initiated multiple
      courses of three weekly hylan G-F 20 injections. All local AEs (knee pain and
      swelling) were qualitatively and quantitatively assessed. The incidence of
      treatment-related local AEs was 3.4% of patients (0.8% of injections) at course
      1, 13.1% of patients (4.3% of injections) at course 2, and 17.3% of patients
      (5.4% of injections) at course 3. The majority of related local AEs were mild to
      moderate and persisted for < or = 48 hours. The number of patients who
      discontinued injections because of local AEs was low. While the incidence of
      local AEs with hylan G-F 20 tends to slightly increase with subsequent courses of
      therapy, physicians should educate patients regarding this possibility rather
      than preclude them from the benefit of continued OA pain relief with repeat hylan
      G-F 20 therapy.

PMID- 16603114
TI  - A surgical tip for shoulder hemiarthroplasty in a patient with a deficient
      rotator cuff.
AB  - The deltopectoral approach has long been the workhorse for exposure of the
      shoulder. However, this exposure involves dividing the subscapularis tendon.
      Despite meticulous repair, suboptimal return of subscapularis may further reduce
      a patient's functional capacity with an already deficient rotator cuff. This
      report describes an alternative approach for shoulder hemiarthroplasty,
      preserving subscapularis, in a patient with a deficient rotator cuff.

PMID- 16603116
TI  - Detecting disulfide crosslinks of high-molecular weight complexes in mouse SVS
      proteins by diagonal electrophoresis.

PMID- 16603117
TI  - Construction of pcDNA3.1-based vectors with blasticidin and puromycin resistance
      markers.

PMID- 16603118
TI  - Analysis of asymmetric dimethylarginine in plasma by HPLC using a monolithic
      column.

PMID- 16603119
TI  - Luminescent metal-ligand complexes as probes of macromolecular interactions and
      biopolymer dynamics.
AB  - The knowledge of microsecond dynamics is important for an understanding of the
      mechanism and function of biological systems. Fluorescent techniques are well
      established in biophysical studies, but their applicability to probe microsecond
      timescale processes is limited. Luminescent metal-ligand complexes (MLCs) have
      created interest mainly due to their unique luminescent properties, such as the
      exceptionally long decay times and large fundamental anisotropy values, allowing
      examination of microsecond dynamics by fluorescence methods. MLC properties also
      greatly simplify instrumentation requirements and enable the use of light
      emitting diode excitation for time-resolved measurements. Recent literature
      illustrates how MLC labels take full advantage of well developed fluorescence
      techniques and how those methods can be extended to timescales not easily
      accessible with nanosecond probes. MLCs are now commercially available as
      reactive labels which give researchers access to methods that previously required
      more complex approaches. The present paper gives an overview of the applications
      of MLC probes to studies of molecular dynamics and interactions of proteins,
      membranes and nucleic acids.

PMID- 16603120
TI  - Oxalate-containing phytocomplexes as dentine desensitisers: an in vitro study.
AB  - It is known that pulpal fluid movement through dentinal tubules causes dentinal
      hypersensitivity and that pain can be reduced by decreasing the fluid flow. The
      aim of this study was to evaluate dentinal permeability and morphology after a
      single exposure to experimental phytocomplex substances containing oxalates. The
      treatments tested were experimental pastes, gels and solutions of phytocomplexes
      (extracted from rhubarb, spinach and mint), an experimental paste containing 5%
      potassium oxalate, and two commercial toothpastes recommended for dentinal
      hypersensitivity (Elmex and Sensodyne). Dentine discs from human third molars
      were used in this study. Each sample was brushed for 3 min with each treatment in
      order to test reductions in dentinal permeability. Each treated sample was
      challenged with orthophosphoric acid for 90 s to determine changes in dentinal
      permeability and the sensitivity of treatments to acid challenge. Scanning
      electron microscopy was used to analyse the samples. This study found that
      spinach and rhubarb phytocomplex treatments reduced dentinal permeability by
      occluding dentinal tubules through formation of calcium oxalate crystals. These
      results indicate that phytocomplexes extracted from rhubarb and spinach, used in
      different formulations, should be effective for topical treatment of dentinal
      hypersensitivity.

PMID- 16603121
TI  - Regulation of Na+/H+ exchanger-NHE3 by angiotensin-II in OKP cells.
AB  - Previous studies have shown that circulating Angiotensin II (A-II) increases
      renal Na+ reabsorption via elevated Na+/H+ exchanger isoform 3 (NHE3) activity.
      We hypothesized that prolonged exposure to A-II leads to an increased expression
      of renal NHE3 by a transcriptionally mediated mechanism. To test this hypothesis,
      we utilized the proximal tubule-like OKP cell line to evaluate the effects of 16
      h treatment with A-II on NHE3 activity and gene expression. A-II significantly
      stimulated NHE3-mediated, S-3226-sensitive Na+/H+ exchange. Inhibition of
      transcription with actinomycin D abolished the stimulatory effect of A-II on NHE3
      mediated pH recovery in acid-loaded OKP cells. This prolonged exposure to A-II
      was also found to elevate endogenous NHE3 mRNA (by 40%)-an effect also abolished
      by inhibition of gene transcription. To evaluate the molecular mechanism by which
      A-II regulates NHE3 expression, the activity of NHE3 promoter driven reporter
      gene was analyzed in transient transfection assays. In transfected OKP cells, rat
      NHE3 promoter activity was significantly stimulated by A-II treatment, and
      preliminary mapping indicated that the A-II responsive element(s) is present
      between 149 and 548 bp upstream of the transcription initiation site in the NHE3
      gene promoter. We conclude that a transcriptional mechanism is at least partially
      responsible for the chronic effects of A-II treatment on renal NHE3 activity.

PMID- 16603122
TI  - Effect of salt on the interactions of antimicrobial peptides with zwitterionic
      lipid bilayers.
AB  - The effect of salt on the binding of the antimicrobial peptide magainin to POPC
      lipid bilayers is studied by 40-50 ns molecular dynamics simulations of a POPC
      bilayer in the presence of different concentrations of Na+ and Cl- ions,
      corresponding to effective concentrations of 0, 100, 150, 200, 250 and 300
      millimolar NaCl, with and without a single molecule of antimicrobial peptide
      magainin. Simulations without magainin showed that increasing salt concentration
      leads to the decrease in the area per lipid, a decrease in the head group tilt of
      the lipids, as well as increased order of lipid tails, in agreement with other
      recent simulations. Simulations with magainin show that peptide binding to the
      lipids is stronger at lower concentrations of salt. The peptides disorder the
      lipids in their immediate vicinity, but this effect is diminished as the salt
      concentration increases. Our studies indicate that while 50 ns simulations give
      information on peptide hydrogen bonding and lipid tail ordering that is
      insensitive to the initial peptide orientation, this run time is not sufficient
      to equilibrate the peptide position and orientation within the bilayer.

PMID- 16603123
TI  - Characterization and regulation of the bovine stearoyl-CoA desaturase gene
      promoter.
AB  - The bovine stearoyl-CoA desaturase (Scd) gene plays an important role in the
      bovine mammary gland where substrates such as stearic and vaccenic acids are
      converted to oleic acid and conjugated linoleic acid (CLA), respectively. Up to
      90% of the CLA in bovine milk is formed due to the action of this enzyme in the
      mammary gland. The areas of the bovine promoter of importance in regulating this
      key enzyme were examined and an area of 36bp in length was identified as having a
      critical role in transcriptional activation and is designated the Scd
      transcriptional enhancer element (STE). Electrophoretic mobility shift assay
      detected three binding complexes on this area in Mac-T cell nuclear extracts.
      Treatment of cells with CLA caused a significant reduction in transcriptional
      activity, with this effect being mediated through the STE region. The bovine Scd
      gene promoter was up-regulated by insulin and down-regulated by oleic acid.

PMID- 16603124
TI  - Alpha-lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase
      transgenic mice.
AB  - Alpha-lipoic acid (alpha-LA) mimics the hypothalamic actions of leptin on food
      intake, energy expenditure, and activation of AMP-activated protein kinase
      (AMPK). To determine if, like leptin, alpha-LA protects against cardiac
      lipotoxicity, alpha-LA was fed to transgenic mice with cardiomyocyte-specific
      overexpression of the acyl CoA synthase (ACS) gene. Untreated ACS-transgenic mice
      died prematurely with increased triacylglycerol content and dilated
      cardiomyopathy, impaired systolic function and myofiber disorganization,
      apoptosis, and interstitial fibrosis on microscopy. In alpha-LA-treated ACS
      transgenic mice heart size, echocardiogram and TG content were normal. Plasma TG
      fell 50%, hepatic-activated phospho-AMPK rose 6-fold, sterol regulatory element
      binding protein-1c declined 50%, and peroxisome proliferator-activated receptor
      gamma cofactor-1alpha mRNA rose 4-fold. Since food restriction did not prevent
      lipotoxicity, we conclude that alpha-LA treatment, like hyperleptinemia, protects
      the heart of ACS-transgenic mice from lipotoxicity.

PMID- 16603125
TI  - Novel Nox inhibitor of oxLDL-induced reactive oxygen species formation in human
      endothelial cells.
AB  - In this study, we investigated effects of a novel NAD(P)H oxidase (Nox)-inhibitor
      3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine (VAS2870) on
      oxidized low-density lipoprotein (oxLDL)-mediated reactive oxygen species (ROS)
      formation in human endothelial cells. Primary cultures of human umbilical vein
      endothelial cells were cultured to confluence and ROS formation was induced with
      50microg/ml oxLDL for 2h. ROS formation was detected by chemiluminescence (CL)
      using the Diogenes reagent. OxLDL induced ROS formation in human endothelial
      cells (171+/-12%; n=10, P<0.05 vs. control). This augmented ROS formation in
      response to oxLDL was completely inhibited by the Nox inhibitor VAS2870 (101+/
      9%; n=7, P<0.05 vs. oxLDL). Similar results were obtained with superoxide
      dismutase (91+/-7%; n=7, P<0.05 vs. oxLDL). However, the Nox4 mRNA expression
      level was neither changed by oxLDL nor VAS2870. We conclude that VAS2870 could
      provide a novel strategy to inhibit the augmented endothelial superoxide anion
      formation in response to cardiovascular risk factors.

PMID- 16603126
TI  - ZmPUMP encodes a fully functional monocot plant uncoupling mitochondrial protein
      whose affinity to fatty acid is increased with the introduction of a His pair at
      the second matrix loop.
AB  - Uncoupling proteins (UCPs) are specialized mitochondrial transporter proteins
      that uncouple respiration from ATP synthesis. In this study, cDNA encoding maize
      uncoupling protein (ZmPUMP) was expressed in Escherichia coli and recombinant
      ZmPUMP reconstituted in liposomes. ZmPUMP activity was associated with a linoleic
      acid (LA)-mediated H(+) efflux with K(m) of 56.36+/-0.27microM and V(max) of
      66.9micromolH(+)min(-1)(mgprot)(-1). LA-mediated H(+) fluxes were sensitive to
      ATP inhibition with K(i) of 2.61+/-0.36mM (at pH 7.2), a value similar to those
      for dicot UCPs. ZmPUMP was also used to investigate the importance of a histidine
      pair present in the second matrix loop of mammalian UCP1 and absent in plant
      UCPs. ZmPUMP with introduced His pair (Lys155His and Ala157His) displayed a 1.55
      fold increase in LA-affinity while its activity remained unchanged. Our data
      indicate conserved properties of plant UCPs and suggest an enhancing but not
      essential role of the histidine pair in proton transport mechanism.

PMID- 16603127
TI  - Expression profilings of 39 genes selected by ANOVA could separate precursors of
      murine dendritic cells and macrophages.
AB  - Dendritic cells (DCs) and macrophages share some stages in the development and
      function of antigen presentation. But it is difficult to separate them from their
      precursors. We used one-way ANOVA (analysis of variances) on murine expression
      profilings of several hematopoietic cells associated with DCs and macrophages to
      find the genes with great differences across the cell groups. These groups were
      the DCs from spleen, cultivated DCs, DC precursors, DC progenitors, DC progenitor
      cell lines, hematopoietic stem cell (HSC), and bone marrow-derived macrophages.
      The data of expression profilings were all downloaded from GEO and ArrayExpress
      database. After the normalization of 11 housekeeping genes across 42 arrays, we
      got 39 genes (44 probesets) by analysis of one-way ANOVA (Bonferroni step-down)
      with p values cutoff of 0.05. These genes (probesets) could separate the
      hematopoietic cells well by the methods of unsupervised hierarchical clustering
      and principal component analysis (PCA). The class prediction also indicated that
      these genes could separate the precursors of DC and macrophages with 20 arrays
      composed of 5 cell types with the same normalization. The accuracy rate of class
      prediction was 90% (18/20). The genes selected by one-way ANOVA included those of
      MHC (major histocompatibility complex) and defense of immunity, cell adhesion,
      chemokine or its receptors, and transcription factors. The results indicated that
      these 39 genes could separate precursors of DC and macrophages very clearly. It
      was suggested that these genes might represent some important molecules that
      related with the precursors of DCs and macrophages, and were worthy for further
      study.

PMID- 16603128
TI  - Effects of different magnitudes of mechanical strain on Osteoblasts in vitro.
AB  - In addition to systemic and local factors, mechanical strain plays a crucial role
      in bone remodeling during growth, development, and fracture healing, and
      especially in orthodontic tooth movement. Although many papers have been
      published on the effects of mechanical stress on osteoblasts or osteoblastic
      cells, little is known about the effects of different magnitudes of mechanical
      strain on such cells. In the present study, we investigated how different
      magnitudes of cyclic tensile strain affected osteoblasts. MC3T3-E1 osteoblastic
      cells were subjected to 0%, 6%, 12% or 18% elongation for 24h using a Flexercell
      Strain Unit, and then the mRNA and protein expressions of osteoprotegerin (OPG)
      and receptor activator of nuclear factor-kappaB ligand (RANKL) were examined. The
      results showed that cyclic tensile strain induced a magnitude-dependent increase
      (0%, 6%, 12%, and 18%) in OPG synthesis and a concomitant decrease in RANKL mRNA
      expression and sRANKL release from the osteoblasts. Furthermore, the induction of
      OPG mRNA expression by stretching was inhibited by indomethacin or genistein, and
      the stretch-induced reduction of RANKL mRNA was inhibited by PD098059. These
      results indicate that different magnitudes of cyclic tensile strain influence the
      biological behavior of osteoblasts, which profoundly affects bone remodeling.

PMID- 16603129
TI  - Crystal structures of the catalytic domain of human stromelysin-1 (MMP-3) and
      collagenase-3 (MMP-13) with a hydroxamic acid inhibitor SM-25453.
AB  - Crystal structures of the catalytic domain of human stromelysin-1 (MMP-3) and
      collagenase-3 (MMP-13) with a hydroxamic acid inhibitor SM-25453 have been solved
      at 2.01 and 2.37A resolutions, respectively. The results revealed that the
      binding modes for this inhibitor to MMP-3 and -13 were quite similar. However,
      subtle comparative differences were observed at the bottom of S1' pockets, which
      were occupied with the guanidinomethyl moiety of the inhibitor. A remarkable
      feature of the inhibitor was the deep penetration of its long aliphatic chain
      into the S1' pocket and exposure of the guanidinomethyl moiety to the solvent.

PMID- 16603130
TI  - Relation between mRNA expression and sequence information in Desulfovibrio
      vulgaris: combinatorial contributions of upstream regulatory motifs and coding
      sequence features to variations in mRNA abundance.
AB  - The context-dependent expression of genes is the core for biological activities,
      and significant attention has been given to identification of various factors
      contributing to gene expression at genomic scale. However, so far this type of
      analysis has been focused either on relation between mRNA expression and non
      coding sequence features such as upstream regulatory motifs or on correlation
      between mRNA abundance and non-random features in coding sequences (e.g., codon
      usage and amino acid usage). In this study multiple regression analyses of the
      mRNA abundance and all sequence information in Desulfovibrio vulgaris were
      performed, with the goal to investigate how much coding and non-coding sequence
      features contribute to the variations in mRNA expression, and in what manner they
      act together. Using the AlignACE program, 442 over-represented motifs were
      identified from the upstream 100bp region of 293 genes located in the known
      regulons. Regression of mRNA expression data against the measures of coding and
      non-coding sequence features indicated that 54.1% of the variations in mRNA
      abundance can be explained by the presence of upstream motifs, while coding
      sequences alone contribute to 29.7% of the variations in mRNA abundance.
      Interestingly, most of contribution from coding sequences is overlapping with
      that from upstream motifs; thereby a total of 60.3% of the variations in mRNA
      abundance can be explained when coding and non-coding information was included.
      This result demonstrates that upstream regulatory motifs and coding sequence
      information contribute to the overall mRNA expression in a combinatorial rather
      than an additive manner.

PMID- 16603132
TI  - Dopaminergic modulation of semantic priming in healthy volunteers.
AB  - BACKGROUND: Semantic priming is a function related to prefrontal cortical (PFC)
      networks and is lateralized. There is evidence that semantic priming underlies
      dopaminergic modulation. It is known that the D1-receptor is more abundant in
      prefrontal networks; however, until now there have been no studies investigating
      the selective modulation of semantic priming with dopamine agonists. Furthermore,
      D1 receptor dysfunction has been described in schizophrenia, and patients with
      formal thought disorder seem to have disturbed focusing of associations and
      increased indirect priming. METHODS: With a subtraction design, we compared the
      influence of pergolide (D1/D2 agonist) with bromocriptine (D2 agonist) and
      placebo, in a randomized, double-blind, crossover design in 40 healthy male
      volunteers. Subjects performed a lateralized lexical decision task including
      direct and indirect related prime-target pairs (stimulus onset asynchrony = 750
      msec). RESULTS: Only on pergolide a decrease of the indirect priming in the left
      hemisphere presentations was found. CONCLUSIONS: These findings point to a
      potential selective modulation of agonists with a D1 component on the focusing of
      semantic associations. The clinical relevance of this study is that it might help
      the development of therapeutic strategies for treating cognitive deficits in
      schizophrenia and Parkinson's disease, which are highly relevant to the
      functional outcome.

PMID- 16603131
TI  - Cortisol levels and hippocampus volumes in healthy preadolescent children.
AB  - BACKGROUND: Research in animal models has demonstrated that elevated levels of
      glucocorticoids can inflict damage within the hippocampus. In adult humans,
      elevated cortisol levels have been associated with reduced hippocampal volumes;
      however, normative data in children are not available. The objective of this
      study was to examine possible associations of serum cortisol levels with
      hippocampal volumes and morphology in healthy children. METHODS: Morning serum
      cortisol levels and hippocampus magnetic resonance imaging were measured in 17
      healthy children (8 girls, 9 boys) between 7 and 12 years of age. RESULTS:
      Cortisol levels were not associated with total hippocampal volumes; however, with
      an analysis of surface morphology, significant associations were found for
      regionally specific portions of the hippocampus. Positive associations were
      detected for the anterior segment of the hippocampus and inverse associations
      along the lateral aspects of the hippocampus. CONCLUSIONS: Associations of
      cortisol levels with regionally specific variations in hippocampal morphology
      were detected during early development in healthy preadolescent children.

PMID- 16603133
TI  - Increased amygdala activity during successful memory encoding in adolescent major
      depressive disorder: An FMRI study.
AB  - BACKGROUND: Although major depressive disorder (MDD) represents one of the most
      serious psychiatric problems afflicting adolescents, efforts to understand the
      neural circuitry of adolescent MDD have lagged behind those of adult MDD. This
      study tests the hypothesis that adolescent MDD is associated with abnormal
      amygdala activity during evocative-face viewing. METHODS: Using functional
      magnetic resonance imaging (fMRI), between-group differences among MDD (n = 10),
      anxious (n = 11), and non-psychiatric comparisons (n = 23) were examined during
      successful vs. unsuccessful face encoding, with encoding success measured post
      scan. RESULTS: Compared to healthy adolescents, MDD patients exhibited poorer
      memory for faces. fMRI analyses accounted for this performance difference through
      event-related methods. In an analysis comparing successful vs. unsuccessful face
      encoding, MDD patients exhibited greater left amygdala activation relative to
      healthy and anxious youth. CONCLUSIONS: Given prior findings among adults, this
      study suggests that adolescent and adult MDD may involve similar underlying
      abnormalities in amygdala functioning.

PMID- 16603134
TI  - Striatal dysfunction in schizophrenia and unaffected relatives.
AB  - BACKGROUND: Schizophrenia has been frequently associated with impaired inhibitory
      control. Such control is known to involve the striatum. Here, we investigate
      whether impaired inhibitory control is associated with abnormal striatal
      activation in schizophrenia. First-degree relatives of patients were also tested
      to examine whether striatal abnormality is associated with schizophrenia, or with
      the risk for the illness. METHODS: Both functional MRI and behavioral data were
      acquired during a task designed to invoke inhibitory control in 21 patients, 15
      unaffected siblings, and 36 matched controls. Subjects must refrain from
      responding to designated stop cues occurring within a series of motor cues.
      Subjects could anticipate the occurrence of stop cues as the likelihood of these
      cues increased in a linear fashion throughout the task. RESULTS: Control subjects
      showed striatal activation while responding to motor cues. This activation
      increased in a linear fashion when the likelihood of having to inhibit the
      response was increased. Both patients siblings did not show anticipation-related
      increase in either striatal activation. However, only patients showed behavioral
      impairments. CONCLUSIONS: Striatal abnormalities occur in schizophrenia patients
      and unaffected siblings. Thus striatal abnormalities may be related to an
      increased (genetic) risk to develop schizophrenia.

PMID- 16603135
TI  - Tryptophan depletion affects heart rate variability and impulsivity in remitted
      depressed patients with a history of suicidal ideation.
AB  - BACKGROUND: Depression is a major risk factor for cardiovascular disease. An
      important risk factor for cardiovascular disease, low heart rate variability,
      often has been found in depressed patients and has been associated with
      impulsivity. The present study investigated whether experimental lowering of
      serotonin would decrease heart rate variability and increase impulsivity in
      remitted depressed patients, in particular in those patients with disturbed
      impulse control. METHODS: Nineteen patients in remission from depression received
      high-dose and low-dose acute tryptophan depletion in a randomized,
      counterbalanced, double-blind crossover design. Heart rate variability and
      impulsivity were assessed during each acute tryptophan depletion session and
      during a baseline session. Suicidal ideation during past depression was used as
      an index for individual differences in impulse control. RESULTS: High-dose acute
      tryptophan depletion led to a larger increase in depressive symptoms than did low
      dose acute tryptophan depletion. High-dose acute tryptophan depletion decreased
      heart rate variability and increased impulsivity and anxiety, but only in
      patients with a history of suicidal ideation. Symptom effects of high-dose acute
      tryptophan depletion correlated with low heart rate variability at baseline.
      CONCLUSIONS: Depressed patients who have problems with controlling impulsivity
      might be more at risk for developing cardiovascular disease, possibly related to
      increased vulnerability to impaired 5-hydroxytryptamine function.

PMID- 16603136
TI  - Studies on the alpha-(1-->4)- and alpha-(1-->8)-fucosylation of sialic acid for
      the total assembly of the glycan portions of complex HPG-series gangliosides.
AB  - A synthetic study on alpha-(1-->4) and alpha-(1-->8)-fucosylation of sialic acid
      is reported, with the ultimate aim being the total assembly of the glycan portion
      of HPG-series gangliosides. In both types of fucosylations, the combination of a
      phenylthio fucosyl donor and a 1,5-lactamized acceptor provided high-yielding
      glycosylations to afford alpha-fucosyl-sialic acid sequences. The obtained alpha
      Fucp-(1-->8)-NeupNAc glycan having a 1,5-lactam bridge has been successfully
      transformed into the corresponding glycosyl donor.

PMID- 16603137
TI  - Synthesis of 1,4-anhydro-D-fructose and 1,4-anhydro-D-tagatose.
AB  - 1,4-Anhydro-D-fructose and 1,4-anhydro-D-tagatose were prepared from 1,2-O
      isopropylidene-D-glucofuranose via the common intermediate 3,5,6-tri-O-benzyl-D
      glucitol. The title compounds may be interesting anti-oxidants and feature
      activities akin to their natural pyranoid counterpart, 1,5-anhydro-D-fructose.

PMID- 16603138
TI  - A convenient gram-scale synthesis of uridine diphospho(13C6)glucose.
AB  - A simple gram-scale synthesis of uridine diphospho(13C6)glucose is presented from
      D-(13C6)glucose. The critical step uses a 1H-tetrazole-catalyzed coupling of
      2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl-1-phosphate and UMP-morpholidate.
      The uridine diphospho(13C6)glucose was used in the structural identification of
      (1-->3)-beta-D-glucan from Lolium multiflorum.

PMID- 16603139
TI  - Convergent synthesis of a trisaccharide as its 2-(trimethylsilyl)ethyl glycoside
      related to the flavonoid triglycoside from Gymnema sylvestre.
AB  - The glycone part of the flavonoid triglycoside, kaempferol 3-O-beta-D
      glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-galactopyranoside,
      has been synthesized in good yield and stereoselectivity using N-iodosuccinimide
      and HClO4-silica promoted glycosylations of thioglycoside donors.

PMID- 16603140
TI  - Alpha 8 integrin expression is required for maintenance of the smooth muscle cell
      differentiated phenotype.
AB  - OBJECTIVE: Vascular smooth muscle cell (VSMC) de-differentiation is a
      prerequisite for migration from the tunica media to the intima after vascular
      injury. Integrin cell adhesion molecules participate in VSMC phenotype
      modulation. Alpha 8 beta 1 integrin is a differentiation marker of VSMCs and its
      knockdown heightens migration. In the present study, we examined whether or not
      alpha 8 integrin is required for the maintenance of VSMC differentiated
      phenotype. METHODS: Alpha 8 integrin in rat VSMC was knocked down by short
      interference RNA (siRNA) targeting alpha 8 integrin in comparison to a non
      silencing siRNA. Cytoskeletal and morphological changes in VSMC were examined by
      immunofluorescence staining. The expression of phenotype-dependent markers was
      analyzed by immunoblotting. RESULTS: Alpha 8 integrin gene silencing evoked
      drastic changes in characteristics of the VSMC differentiated phenotype,
      including VSMC morphology, actin fibre organization, focal adhesion assembly and
      the expression of phenotype-dependent markers in favor of de-differentiation.
      Then, we investigated whether or not phenotype modulation induced by alpha 8
      integrin gene silencing could be reversed by an inducer of VSMC differentiation.
      Transforming growth factor-beta (TGF-beta) failed to upregulate smooth muscle
      myosin heavy chain as well as the assembly of parallel actin fibres in VSMCs
      transfected by siRNA-alpha 8. In addition, TGF-beta-induced vinculin localization
      at the tip of the cells was impaired by alpha 8 integrin gene silencing.
      CONCLUSION: These data suggest that alpha 8 integrin expression is required for
      maintenance of the VSMC differentiated phenotype, a state that is crucial for non
      motile VSMCs.

PMID- 16603141
TI  - Lipid conformation in crystalline bilayers and in crystals of transmembrane
      proteins.
AB  - Dihedral torsion angles evaluated for the phospholipid molecules resolved in the
      X-ray structures of transmembrane proteins in crystals are compared with those of
      phospholipids in bilayer crystals, and with the phospholipid conformations in
      fluid membranes. Conformations of the lipid glycerol backbone in protein crystals
      are not restricted to the gauche C1-C2 rotamers found invariably in phospholipid
      bilayer crystals. Lipid headgroup conformations in protein crystals also do not
      conform solely to the bent-down conformation, with gauche-gauche configuration of
      the phospho-diester, that is characteristic of phospholipid bilayer membranes.
      This suggests that the lipids that are resolved in crystals of membrane proteins
      are not representative of the entire lipid-protein interface. Much of the chain
      configurational disorder of the membrane-bound lipids in crystals arises from
      energetically disallowed skew conformations. This indicates a configurational
      heterogeneity in the lipids at a single binding site: eclipsed conformations
      occur also in some glycerol backbone torsion angles and C-C torsion angles in the
      lipid headgroups. Stereochemical violations in the protein-bound lipids are
      evidenced by one-third of the ester carboxyl groups in non-planar configurations,
      and certain of the carboxyls in the cis configuration. Some of the lipid
      structures in protein crystals have the incorrect enantiomeric configuration of
      the glycerol backbone, and many of the branched methyl groups in structures of
      the phytanyl chains associated with bacteriorhodopsin crystals are in the
      incorrect S-configuration.

PMID- 16603142
TI  - Serum concentrations of MMP-1, MMP-2, and TIMP-1 in Chinese women: age-related
      changes, and the relationships with bone biochemical markers, bone mineral
      density.
AB  - BACKGROUND: Osteoblast-derived matrix metalloproteinse-1 (MMP-1), MMP-2 and
      tissue inhibitor of metalloproteinase-1 (TIMP-1) play a role in bone metabolism
      by degrading bone matrix. METHODS: We measured MMP-1, MMMP-2, TIMP-1 and
      associated results with age and bone metabolism in 591 Chinese women aged 20-80
      y. RESULTS: Serum MMP-1, MMP-2, and TIMP-1 concentrations exhibited positive
      correlation with age. Serum concentrations of MMP-1 were higher in 40-69 y old
      women. The concentrations of MMP-2 were significantly increased in the 50-69 y
      olds. Serum TIMP-1 concentrations were significantly lower in women aged 30-59 y,
      and then these were followed by an increase at >60 y olds. We found a significant
      negative weaker correlation between MMP-2 and BMD. But multiple linear stepwise
      regression analysis showed that MMP-2 was not a determinant factor for BMD. There
      were significant positive correlations between MMP-2 and bone alkaline
      phosphatase (BAP), osteocalcin (OC), and cross-linked N-telopeptides of type I
      collagen (NTX). CONCLUSIONS: The serum concentrations of MMP-1, MMP-2, and TIMP-1
      exhibit age-related changes, and circulating MMP-2 and bone turnover are related.

PMID- 16603143
TI  - Measurement of plasma antioxidant reserve after supplementation with various
      antioxidants in healthy subjects.
AB  - BACKGROUND: Current methods to estimate antioxidant status of plasma have many
      associated difficulties including questionable sensitivity, unreliability, non
      reproducible results and procedural difficulties. In addition, there is no
      significant elevation in the measured value of biomarkers of oxidative stress
      until pathological disease is already evident. We have developed a new method
      that eliminates many of these problems. METHODS: This new method includes 3
      steps: (1) enzymatic removal of uric acid; (2) ex vivo free radical oxidation of
      plasma by the addition of a free-radical generator such as SIN-1 or AAPH; and (3)
      measurement of a marker of lipid peroxidation, 8-isoprostanes. RESULTS: It has
      been shown in an in vitro experiment that the addition of various antioxidants to
      plasma significantly reduced the amount of free-radical induced 8-isoprostanes.
      In a human single dose supplementation clinical study with vitamin C, vitamin E,
      and grape seed and green tea extracts (on separate days) 8-isoprostane formation
      was also significantly reduced compared to no supplementation (74.2 to 53.8+/-5.1
      pg/ml for vitamin C). CONCLUSIONS: The reduction in 8-isoprostane formation
      demonstrates that the total amount of antioxidant protection in the plasma can be
      increased with supplementation of antioxidants and this new method can
      effectively measure the plasma antioxidant reserve (PAR) in healthy subjects.

PMID- 16603144
TI  - Association of serum transferrin receptor concentration with markers of
      inflammation in Zimbabwean children.
AB  - BACKGROUND: Clinical studies have shown that degree of erythropoiesis, the
      hypoxic response, and iron status each independently influences transferrin
      receptor concentration, but there is conflicting information regarding the effect
      of inflammation on transferrin receptor expression. SUBJECTS AND METHODS: Levels
      of hemoglobin, reticulocytes, serum ferritin, transferrin receptors and
      inflammatory markers (C-reactive protein, interleukin-6 and neutrophils) were
      determined in 208 Zimbabwean children <or=5 years attending well-child clinics in
      a non-malaria transmission, non-hookworm area. RESULTS: In linear regression
      models among 147 children with ferritin >10 ng/mL that adjusted for
      erythropoiesis with log(10) reticulocyte count, the hypoxic response with
      hemoglobin concentration and iron status with log(10) ferritin concentration,
      positive correlations were found between log(10) transferrin receptor
      concentration and log(10) C-reactive protein concentration (P=0.012), log(10)
      interleukin-6 concentration (P=0.011) and log(10) neutrophil count (P=0.013).
      These models predict that, with a baseline transferrin receptor concentration in
      the upper normal range of 8.0 mg/L and holding hemoglobin concentration and
      reticulocyte count constant, an increase from 1 to 10 mg/L in C-reactive protein
      is associated with a rise of 1.6 mg/L in transferrin receptor (95% C.I. 0.3-3.0
      mg/L), an increase from 0.5-to-5.0 pg/mL in interleukin-6 with a rise of 1.9 mg/L
      (0.4-3.7 mg/L), and an increase from 2000 to 20,000/microL in neutrophil count
      with a rise of 3.6 mg/L (0.7-7.5 mg/L). CONCLUSION: Our results suggest that
      inflammation leads to an increase in circulating transferrin receptor
      concentration that is independent of the degree of erythropoiesis, the hypoxic
      response and iron status.

PMID- 16603145
TI  - The diagnostic value of G-CSF measurement in the sera of colorectal cancer and
      adenoma patients.
AB  - BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) regulates the growth of
      hematopoietic progenitor cells. Cancer cells, including colorectal cancer, can
      produce this cytokine. The aim of this study was to compare the diagnostic value
      of measurement of G-CSF and classic tumor markers--carcinoembryonic antigen (CEA)
      and carbohydrate antigen 19-9 (CA 19-9) in the sera of colorectal cancer with
      adenoma patients and to determine its usefulness in the diagnosis of colorectal
      cancer and polyps. PATIENTS AND METHODS: The serum levels of G-CSF and tumor
      markers were assayed in 76 colorectal cancer, 35 colorectal adenoma patients and
      in 65 healthy subjects. We defined the diagnostic sensitivity, specificity and
      areas under ROC curves for the measurands. RESULTS: Median values of G-CSF and
      tumor markers were significantly higher in colorectal cancer patients than those
      in healthy subjects. There were significant differences in the serum levels of G
      CSF between adenoma patients and healthy subjects. The concentrations of tumor
      markers in colorectal cancer patients were higher than those in polyps. Combined
      use of G-CSF with CEA improved their diagnostic sensitivity in colorectal cancer.
      CONCLUSIONS: Measurement of G-CSF might be useful in the diagnosis of colorectal
      cancer patients, but not in the differentiation between colorectal cancer and
      polyps.

PMID- 16603146
TI  - A prospective study of early-pregnancy plasma malondialdehyde concentration and
      risk of preeclampsia.
AB  - OBJECTIVES: Preeclampsia is associated with elevated plasma malondialdehyde
      concentration, but prospective data are scarce. We examined the relation between
      early-pregnancy plasma malondialdehyde and subsequent preeclampsia risk. DESIGN
      AND METHODS: In a nested case-control analysis, we measured malondialdehyde
      concentrations in 22 women who developed preeclampsia and 711 who remained
      normotensive during pregnancy. We calculated adjusted odds ratios (OR) and 95%
      confidence intervals (CI). We repeated analyses after adjustment for early
      pregnancy plasma lipid concentrations, which are related to preeclampsia risk and
      lipid peroxidation measures. RESULTS: After adjustment for confounders,
      preeclampsia risk increased across tertiles of malondialdehyde concentration
      (trend P = 0.04). Further adjustment for triglyceride concentration slightly
      strengthened the association. Middle- and high-tertile malondialdehyde ORs were
      3.2 (CI 0.8-12.2) and 4.2 (1.1-16.0) versus low-tertile exposure. CONCLUSIONS:
      Early-pregnancy plasma malondialdehyde concentration is positively associated
      with subsequent preeclampsia risk independent of plasma lipid concentrations.
      These results support lipid peroxidation as an etiologic component of
      preeclampsia.

PMID- 16603147
TI  - Effect of daily versus twice weekly long-term iron supplementation on iron
      absorption and status in iron-deficient women: a stable isotope study.
AB  - OBJECTIVES: This work aims at studying the effect of daily versus twice weekly
      long-term Fe supplementation on Fe absorption and status in Fe-deficient women.
      DESIGN AND METHODS: The study design is a randomized controlled open study
      carried out in the Internal Medicine Department, CHU de Clermont-Ferrand, France.
      Twenty-four young women participated in this study and were randomized into two
      groups: Group 1 received 50 mg Fe daily, and group 2 received 50 mg Fe twice
      weekly for 3 months. On day 10 (D10) and on day 90 (D90) of Fe supplementation,
      blood samples were obtained, and women received orally about 5 mg of 57Fe, and
      blood was sampled at different times over 24 h. The 57Fe absorption was evaluated
      by calculating the areas under the curves (AUC). Fe and oxidative stress status
      were also assessed. RESULTS: 57Fe absorption was similar in both groups on D10
      but was greatly decreased in Group 1 and remained high in Group 2 on D90. Fe
      status was more improved in Group 1 than in Group 2. Oxidative stress status
      remained statistically unchanged. CONCLUSIONS: Our study shows that daily Fe
      supplementation is able to correct an Fe deficiency much more than twice weekly
      Fe supplementation in young women.

PMID- 16603148
TI  - Effects of window types on classification of carotid artery Doppler signals in
      the early phase of atherosclerosis using complex-valued artificial neural
      network.
AB  - In this study, carotid artery Doppler ultrasound signals were acquired from left
      carotid arteries of 38 patients and 40 healthy volunteers. The patient group had
      an established diagnosis of the early phase of atherosclerosis through coronary
      or aortofemoropopliteal angiographies. Doppler signals were processed using fast
      Fourier transform (FFT) with different window types, Hilbert transform and Welch
      methods. After these processes, Doppler signals were classified using complex
      valued artificial neural network (CVANN). Effects of window types in
      classification were interpreted. Results for three methods and five window types
      (Bartlett, Blackman, Boxcar, Hamming, Hanning) were presented as comparatively.
      CVANN is a new technique for solving classification problems in Doppler signals.
      Furthermore, examining the effects of window types in addition to CVANN in this
      classification problem is also the first study in literature related with this
      subject. Results showed that CVANN, whose input data were processed by Welch
      method for each window types stated above, had classified all training and test
      patterns, which consist of 36 healthy, 34 unhealthy and four healthy, four
      unhealthy subjects, respectively, with 100% classification accuracy for both
      training and test phases.

PMID- 16603149
TI  - Reverse genetic analysis of neurogenesis in the zebrafish retina.
AB  - To gain an understanding of molecular events that underlie pattern formation in
      the retina, we evaluated the expression profiles of over 8000 transcripts
      randomly selected from an embryonic zebrafish library. Detailed analysis of cDNAs
      that display restricted expression patterns revealed factors that are
      specifically expressed in single cell classes and are potential regulators of
      neurogenesis. These cDNAs belong to numerous molecular categories and include
      cell surface receptors, cytoplasmic enzymes, and transcription factors. To test
      whether expression patterns that we have uncovered using this approach are
      indicative of function in neurogenesis, we used morpholino-mediated knockdown
      approach. The knockdown of soxp, a transcript expressed in the vicinity of the
      inner plexiform layer, revealed its role in cell type composition of amacrine and
      ganglion cell layers. Blocking the function of cxcr4b, a chemokine receptor
      specifically expressed in ganglion cells, suggests a role in ganglion cell
      survival. These experiments demonstrate that in situ hybridization-based reverse
      genetic screens can be applied to isolate genetic regulators of neurogenesis.
      This approach very well complements forward genetic mutagenesis studies
      previously used to study retinal neurogenesis in zebrafish.

PMID- 16603150
TI  - Preventive effects of (5R)-5-hydroxytriptolide on concanavalin A-induced
      hepatitis.
AB  - (5R)-5-hydroxytriptolide (LLDT-8) exhibits strong immunosuppressive activities in
      vitro and in vivo. Here, we investigated the effects of LLDT-8 on concanavalin A
      induced hepatitis. Liver damage was evaluated by serum alanine transaminase (ALT)
      level and liver histology. The effects of LLDT-8 were determined by measurement
      of serum cytokines, lymphocyte proliferation assay, flow cytometry analysis of
      splenic T cell percentage and apoptosis, reverse-transcription polymerase chain
      reaction (RT-PCR) analysis for gene transcriptions. In LLDT-8-treated mice, serum
      ALT level and histological damage were markedly attenuated. The beneficial effect
      of LLDT-8 was closely associated with (i) reduction of serum tumor necrosis
      factor-alpha, interferon-gamma (IFN-gamma), interleukin-2, interleukin-12, and
      interleukin-6 levels; (ii) elimination of activated T cells by increasing
      proapoptotic genes signal transducer and activator of transcription 1 (STAT1) and
      interferon regulatory factor-1 (IRF-1) expression in spleens; (iii) blockade of
      mRNA expressions for chemokines (monokine induced by IFN-gamma, Mig; IFN-gamma
      inducible protein-10, IP-10; IFN-inducible T cell-alpha chemoattractant, I-TAC),
      vascular adhesion molecule-1 (VCAM-1), and chemokine receptors (C-C chemokine
      receptor 1, CCR1; C-C chemokine receptor 5, CCR5; C-X-C chemokine receptor 3,
      CXCR3) in livers. These results suggested the therapeutic potential of LLDT-8 in
      IFN-gamma/STAT1/IRF-1 signaling- and inflammatory cytokines-mediated immune
      disorders.

PMID- 16603151
TI  - The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of
      cocaine in marmoset monkeys.
AB  - Brain neuropeptide transmitters of the tachykinin family are involved in the
      organization of many behaviors. However, little is known about their contribution
      to the behavioral effects of drugs of abuse. Recently, the tachykinin NK3
      receptor, one of the three tachykinin receptors in the brain, was shown to
      attenuate the acute and chronic behavioral effects of cocaine in rats. In order
      to test if these findings can be generalized to primates we investigated the role
      of the tachykinin NK3 receptor in the acute behavioral effects of cocaine in
      marmoset monkeys (Callithrix penicillata) using a figure-eight maze procedure.
      Animals were pretreated with the tachykinin NK3 receptor antagonist, (R)-(N)-[1
      [3-[1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl]propyl]-4-phenylpiperidin-4
      yl]-N-methylacetamide (SR142801; 0, 0.02, 0.2, 2.0 mg/kg, i.p.), and received
      either a treatment with cocaine (10 mg/kg, i.p) or saline (i.p.). Cocaine
      increased locomotor activity and aerial glance behavior, but reduced exploratory
      and bodycare activities, scent marking and terrestrial scanning behavior. A
      sensitivity analysis revealed that two responder types can be differentiated in
      relation to the occurrence of a hyperlocomotor response to cocaine. SR142801
      blocked the actions of cocaine on several behaviors dose-dependently for each
      responder type, respectively. There was no effect of SR142801 alone on any
      behavior measured. These data suggest that the tachykinin NK3 receptor
      contributes to the individual behavioral response to cocaine in marmoset monkeys.
      Having no behavioral effects on its own, but blocking the cocaine effects, might
      suggest the tachykinin NK3 receptor antagonist, SR142801, as a potential
      treatment of cocaine addiction in humans.

PMID- 16603152
TI  - Potent analgesic effects of a putative sodium channel blocker M58373 on formalin
      induced and neuropathic pain in rats.
AB  - M58373, 4-[2-(4-hydroxy-4-{[N-(4-isopropoxyphenyl)-N-methylamino]methyl}piperidin
      1-yl)ethyl]benzonitrile monohydrochloride, is a novel compound, which has an
      inhibitory activity on neurotoxin binding to the site 2 of voltage-gated sodium
      channels. In this study, we investigated the effects of M58373 on substance P
      release from sensory neurons in vitro and pain behaviors/responses in rats,
      compared with mexiletine. M58373 (1-10 microM) inhibited veratridine-induced
      release of substance P from dorsal root ganglion cells. In the formalin test,
      oral M58373 (0.3-10 mg/kg) reduced the time spent in nociceptive behaviors only
      in the late phase. In the neuropathic pain model, oral M58373 (1-10 mg/kg)
      attenuated mechanical allodynia and heat hyperalgesia in the nerve-injured paw
      without affecting normal responses in the uninjured paw. In contrast, oral
      mexiletine (10-100 mg/kg) had a narrow therapeutic dose range in both models
      because of the adverse effects on the central nervous system. These results
      suggest that M58373 is a favorable prototype for novel anti-neuropathic pain
      agents.

PMID- 16603154
TI  - Ferritin forms dynamic oligomers to associate with microtubules in vivo:
      implication for the role of microtubules in iron metabolism.
AB  - Ferritin, a ubiquitously distributed iron storage protein, has been reported to
      interact with microtubules in vitro (Hasan et al., 2005, FEBS journal 272:822
      831). Here, we demonstrate that ferritin binds with the microtubules in an
      oligomeric form and that the microtubule-bound ferritin contains more than two
      fold amount of iron compared to the unbound ferritin fraction in vitro. Indirect
      immunofluorescence microscopy showed that a significant fraction of the ferritin
      molecules colocalized with the microtubules as oligomers in a wide variety of
      cell lines. These findings are consistent with the immediate oligomerization of
      rhodamine-labeled ferritin, microinjected in living human hepatoma cells.
      Ferritin oligomers were dynamic in the cytoplasm, and an anti-microtubule drug
      significantly inhibited their intracellular movement. Treatment of cells with an
      iron donor, ferric ammonium citrate, remarkably increased the number of cells
      containing ferritin oligomers. On the other hand, when the cells, such as mouse
      neuroblastoma cells, were deprived of iron, ferritin oligomers were localized in
      the microtubule dense, neurite shafts, but were disappeared from the microtubule
      deficient neurite tips. These data indicate that the microtubules provide a
      scaffold for the cytoplasmic distribution and transport of the iron-rich ferritin
      and implicate the role of microtubules in iron metabolism.

PMID- 16603153
TI  - Poloxamer 407 (P-407)-mediated reduction in the gene expression of ATP-binding
      cassette transporter A1 may contribute to increased cholesterol in peripheral
      tissues of P-407-treated rats.
AB  - The purpose of this study was to determine whether poloxamer 407, a chemical
      known to increase plasma lipid levels in rodents following parenteral
      administration, decreased the gene expression of ATP-binding-cassette transporter
      A1. Using human macrophages cultured with poloxamer 407, there was a significant
      reduction in the gene expression of ATP-binding-cassette transporter A1; however,
      there was no effect on the gene expression of either fatty acid synthase or
      sterol regulatory element binding protein-1. Reduction of ATP-binding-cassette
      transporter A1 mRNA levels was also observed in both liver and intestine of
      poloxamer 407-treated rats. When macrophages were cultured with poloxamer 407,
      the percent of cholesterol effluxed decreased in a concentration-dependent
      fashion, both in the absence and presence of a synthetic liver X receptor
      agonist. Lastly, total and unesterified (free) cholesterol concentrations were
      determined in the liver and 9 peripheral tissues of poloxamer 407- and saline
      injected (control) rats. In every tissue, the concentration of total cholesterol
      for poloxamer 407-treated rats was significantly greater than the corresponding
      value for controls. Our findings would seem to suggest that the poloxamer 407
      mediated reduction in both ATP-binding-cassette transporter A1 gene expression
      and cellular cholesterol efflux may potentially be one factor that contributes to
      the accumulation of cholesterol and cholesteryl esters in the liver and 9
      peripheral tissues of poloxamer 407-treated rats. Furthermore, the surprising
      specificity by poloxamer 407 for inhibition of ATP-binding-cassette transporter
      A1 gene expression over fatty acid synthase and sterol regulatory element binding
      protein-1 may potentially be due to either disruption of a transcriptional
      cofactor required for ATP-binding-cassette transporter A1 gene expression, or
      enhanced turnover of ATP-binding-cassette transporter A1 mRNA.

PMID- 16603155
TI  - The use of small interfering RNAs to inhibit adipocyte differentiation in human
      preadipocytes and fetal-femur-derived mesenchymal cells.
AB  - RNA interference (RNAi) has been used in functional genomics and offers
      innovative approaches in the development of novel therapeutics. Human mesenchymal
      stem cells offer a unique cell source for tissue engineering/regeneration
      strategies. The current study examined the potential of small interfering RNAs
      (siRNA) against human peroxisome proliferator activated receptor gamma
      (PPARgamma) to suppress adipocyte differentiation (adipogenesis) in human
      preadipocytes and fetal-femur-derived mesenchymal cells. Adipogenesis was
      investigated using cellular and biochemical analysis. Transient transfection with
      PPARgamma-siRNA using a liposomal-based strategy resulted in a significant
      inhibition of adipogenesis in human preadipocytes and fetal-femur-derived
      mesenchymal cells, compared to controls (cell, liposomal and negative siRNA). The
      inhibitory effect of PPARgamma-siRNA was supported by testing human PPARgamma
      mRNA and adipogenic associated genes using reverse transcription polymerase chain
      reaction (RT-PCR) to adiponectin receptor 1 and 2 as well as examination of fatty
      acid binding protein 3 (FABP3) expression, an adipocyte-specific marker. The
      current studies indicate that PPARgamma-siRNA is a useful tool to study
      adipogenesis in human cells, with potential applications both therapeutic and in
      the elucidation of mesenchymal cell differentiation in the modulation of cell
      differentiation in human mesenchymal cells.

PMID- 16603156
TI  - Dynamic neuronal responses in cortical and thalamic areas during different phases
      of formalin test in rats.
AB  - Although formalin-induced activity in primary afferent fibers and spinal dorsal
      horn is well described, the forebrain neural basis underlying each phase of
      behavior in formalin test has not yet been clarified. The present study was
      designed to investigate the cortical and thalamic neuronal responses and
      interactions among forebrain areas during different phases after subcutaneous
      injection of formalin. Formalin-induced neuronal activities were simultaneously
      recorded from primary somatosensory cortex (SI), anterior cingulate cortex (ACC)
      and medial dorsal (MD) and ventral posterior (VP) thalamus during different
      phases (i.e., first phase, interphase, second phase and third recovery phase
      starting from 70 min after injection) of formalin test, using a multi-channel,
      single-unit recording technique. Our results showed that, (i) unlike the
      responses in primary afferent fibers and spinal dorsal horn, many forebrain
      neurons displayed monophasic excitatory responses in the first hour after
      formalin injection, except a small portion of neurons which exhibited biphasic
      responses; (ii) the response patterns of many cortical and thalamic neurons
      changed from excitatory to inhibitory at the end of the second phase; (iii) the
      direction of information flow also changed dramatically, i.e., from cortex to
      thalamus and from the medial to the lateral pathway in the first hour, but
      reversed in phase 3. These results indicate that the changes of activity pattern
      in forebrain networks may underlie the emerging and subsiding of central
      sensitization-induced pain behavior in the second phase of formalin test.

PMID- 16603157
TI  - Leishmania amazonensis: Biological and biochemical characterization of ecto
      nucleoside triphosphate diphosphohydrolase activities.
AB  - The presence of Leishmania amazonensis ecto-nucleoside triphosphate
      triphosphohydrolase activities was demonstrated using antibodies against
      different NTPDase members by Western blotting, flow cytometry, and immunoelectron
      microscopy analysis. Living promastigote cells sequentially hydrolyzed the ATP
      molecule generating ADP, AMP, and adenosine, indicating that this surface enzyme
      may play a role in the salvage of purines from the extracellular medium. The L.
      amazonensis ecto-NTPDase activities were insensitive to Triton X-100, but they
      were enhanced by divalent cations, such as Mg(2+). In addition, the ecto-NTPDase
      activities decreased with time for 96 h when promastigotes were grown in vitro.
      On the other hand, these activities increased considerably when measured in
      living amastigote forms. Furthermore, the treatment with adenosine, a mediator of
      several relevant biological phenomena, induced a decrease in the reactivity with
      anti-CD39 antibody, raised against mammalian E-NTPDase, probably because of down
      regulation in the L. amazonensis ecto-NTPDase expression. Also, adenosine and
      anti-NTPDase antibodies induced a significant diminishing in the interaction
      between promastigotes of L. amazonensis and mouse peritoneal macrophages.

PMID- 16603158
TI  - The fission yeast stress MAPK cascade regulates the pmp3+ gene that encodes a
      highly conserved plasma membrane protein.
AB  - In eukaryotic organisms, stress-activated mitogen-activated protein kinases
      (MAPK) play crucial roles in transmitting environmental signals to regulate gene
      expression for cellular stress adaptation. Here we report that, in the fission
      yeast Schizosaccharomyces pombe, Spc1/Sty1 MAPK and the Atf1 transcription factor
      regulate the stress-induced expression of Pmp3, a ubiquitous small membrane
      protein implicated in the modulation of the plasma membrane potential. The pmp3
      null mutant, as well as the spc1 and atf1 mutants, is hypersensitive to the
      cationic antibiotic hygromycin B. Transcriptional regulation of the Pmp3-like
      genes by the stress-activated MAPK may also be conserved in other eukaryotes,
      including plants.

PMID- 16603159
TI  - Effect of progesterone supplementation in early pregnancy on the pregnancy
      outcome after in vitro fertilization.
AB  - A retrospective cohort study was performed to evaluate IVF clinical pregnancy
      rates and livebirth rates between patients receiving progesterone supplementation
      through the first trimester of pregnancy (first trimester protocol) at 12 weeks
      vs. discontinuation after a positive beta-hCG test 2 weeks after retrieval
      (luteal protocol) at 4 weeks of pregnancy. A similar rate of clinical pregnancies
      occurred at 7 weeks (81.8% luteal protocol vs. 85.8% first trimester protocol;
      P=.49) and for livebirth rates (76.8% luteal protocol vs. 75.0% first trimester
      protocol; P=.80), but a trend toward a higher rate of pregnancy loss after 7
      weeks in the first trimester protocol group occurred (15.5% vs. 4.4%; P=.06),
      indicating that first trimester progesterone supplementation may support early
      pregnancy through 7 weeks by delaying miscarriage but does not improve livebirth
      rates.

PMID- 16603160
TI  - Image in reproductive medicine. Cesarean scar ectopic pregnancy.
AB  - Bilateral hypogastric artery ligation followed by dilatation and evacuation under
      laparoscopic guidance was successful in the treatment of an advanced cesarean
      scar ectopic pregnancy. This case presents images of ultrasound, magnetic
      resonance imaging, and gross anatomy unique to cesarean scar pregnancy.

PMID- 16603162
TI  - Confidentiality, privacy and security of patients' health care information.

PMID- 16603161
TI  - Do tribal communities show an inverse relationship between sickle cell disorders
      and glucose-6-phosphate dehydrogenase deficiency in malaria endemic areas of
      Central-Eastern India?
AB  - Tribal communities in India constitute the largest tribal population in the
      world. There are about 635 biological isolates (tribes and subtribes), which
      constituted 8.08% (about 84.3 million) of the total population of India as per
      the 2001 census. Out of 635 scheduled tribes (aborigines), 62 live in the state
      of Orissa alone forming about 10.8% of the tribal population of India. Orissa
      state occupies an important place, being the 3rd in rank for the highest
      concentration of tribal population in the country. In India, tribal communities
      are highly vulnerable to hereditary diseases and have a high degree of
      malnutrition, morbidity and mortality. The sickle cell haemoglobinopathy and
      glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency are important genetic
      and public health problems in Central-Eastern part of India. In order to map out
      these genetic disorders among the tribal people, a cross-section of 15 major
      tribal communities from different parts of Orissa was randomly screened for
      haemoglobin variants and G6PD deficiency. The high frequency of sickle cell
      haemoglobinopathy (0-22.4%) and G6PD deficiency (4.3-17.4%), with beta
      thalassemia trait (0-8.5%) taking almost an intermediate position, was observed.
      For G6PD deficiency, hemizygous males as well as female heterozygotes and female
      homozygotes were detected. Twelve cases showed compound heterozygosity for sickle
      cell haemoglobinopathy and G6PD deficiency. There seems to be a trend towards an
      inverse relationship between the sickle cell allele and G6PD deficiency, and
      sickle cell and beta-thalassemia allele in a cross-section of malaria endemic
      (Plasmodium falciparum) tribal communities in Orissa. When the frequency of
      sickle cell allele decreases in a cross-section of malaria endemic tribal
      population, the frequency of G6PD enzyme deficiency and beta-thalassemia allele
      increases and vice versa. Natural selection had played a major role in favour of
      sickle cell, beta-thalassemia and G6PD mutation alleles so that they had probably
      evolved as a protective mechanism against the lethal effects of malaria in this
      part of the country. However, the calculated values of 0.074, 0.218 and 0.337,
      respectively, of Pearson's correlation co-efficient (r), showed no correlation
      between sickle cell disorders and G6PD deficiency, sickle cell disorders and beta
      thalassemia, and G6PD deficiency and beta-thalassemia.

PMID- 16603163
TI  - Inhibition of Gardnerella vaginalis by lactobacilli.

PMID- 16603164
TI  - Outcome of post-term pregnancies in southern Iran.

PMID- 16603165
TI  - Treatment of intrauterine fetal death by means of a PGE2-filled portio adapter.

PMID- 16603166
TI  - HIV and fertility treatment.

PMID- 16603167
TI  - Conventional and experimental treatment of cerebral malaria.
AB  - The most severe complication of Plasmodium falciparum infection is cerebral
      malaria (CM). Cerebral malaria implies the presence of neurological features,
      especially impaired consciousness. The treatment of CM is limited to: (i) a few
      conventional anti-malarial drugs (quinine or artemisinins), (ii) adjunctive
      treatments (initial stabilisation, blood exchange transfusion, osmotic diuretics
      and correction of hypoglycaemia, acidosis and hypovolaemia) and (iii)
      immunomodulation. There are clear procedures concerning treatment of CM, which
      include the use of the anti-plasmodial drugs. Adjunctive treatments are
      permissible but there is no single official guideline and immune intervention is
      a possibility currently being examined in rodent models only. The suggested
      immunomodulation approach is based on the strong likelihood that CM is the result
      of an immunopathological process. P. falciparum initiates the multifactorial
      chain of events leading to lethal CM and, after a certain stage, it is impossible
      to stop the progression even by using anti-malarial drugs. We present evidence
      that CM is a result of a dysregulated immune response. Therefore, it might be
      prevented by early modulation of discrete factors that participate in this
      process. In experimental systems, some immunomodulators delay or prevent CM
      without affecting the parasitaemia. Therefore, in the future the ultimate
      treatment of CM may be a combination of an anti-malarial and an immunomodulator.
      However, the overall effect of an immunomodulator would need to be carefully
      examined in view of concomitant infections, especially in malaria endemic areas.

PMID- 16603168
TI  - Rapid high-performance liquid chromatography-electrospray ionization tandem mass
      spectrometry method for qualitative and quantitative analysis of virgin olive oil
      phenolic metabolites in human low-density lipoproteins.
AB  - A rapid method for detection and quantification of metabolites of specific olive
      oil phenolic compounds (hydroxytyrosol monoglucuronide, hydroxytyrosol
      monosulfate, tyrosol glucuronide, tyrosol sulfate and homovanillic acid sulfate)
      in low-density lipoprotein (LDL) fractions by solid-phase extraction (SPE) and
      high-performance liquid chromatography coupled to electrospray ionization tandem
      mass spectrometry (HPLC/ESI-MS/MS) is described. A 3 microm particle size fast
      C18 Luna column, 5 cm x 2.0 mm I.D., was used at a flow rate of 0.6 mL/min with a
      mobile phase consisting of 0.1% (v/v) formic acid (A) and acetonitrile (B). A
      linear gradient profile was used for separation at column temperature 40 degrees
      C. The proposed chromatographic procedure is rapid without loosing its separation
      efficiency and sensitivity. Validation proofs were carried out for the method
      described, showing a linear system (r>0.99) and a recovery of 81.9 and 101.3% for
      hydroxytyrosol and homovanillic acid, respectively. The results show that this
      method is effective and can be used in routine analysis.

PMID- 16603169
TI  - Rapid and sensitive determination of aminoglycoside antibiotics in water samples
      using a strong cation-exchange chromatography non-derivatisation method with
      chemiluminescence detection.
AB  - A simple and sensitive chemiluminescence (CL) detection approach was developed
      for the direct analysis of aminoglycoside antibiotics in water samples following
      strong cation-exchange chromatographic (SCX-HPLC) separation. This detection
      system, which eliminates the need for sample derivatisation, is based on the
      inhibitory effect of aminoglycosides on the CL reaction between luminol and
      hydrogen peroxide catalysed by copper(II). As the operational and chemical
      variables that affect the CL signal were optimised, ionic strength and the Triton
      X-100 micelles turned out to be the keys to obtain maximum CL efficiency.
      Aminoglycosides were successfully separated in 10 min on a SCX column using a
      mobile phase consisting of an aqueous solution containing 5.0 x 10(-3)mol/l
      sodium acetate and 0.65 mol/l sodium chloride at pH 6.1. Sample volumes of 50 ml
      were preconcentrated by passage through a weakly acidic IRC-50 exchange column.
      Limits of detection from 0.7 to 10 microg/l and relative standard deviations from
      2.7 to 5.4% were thus obtained. The proposed method surpasses other
      chromatographic alternatives in terms of the limit of detection, sample
      requirements for analysis and cost.

PMID- 16603170
TI  - A stability-indicating high performance liquid chromatographic assay for the
      determination of orlistat in capsules.
AB  - A stability-indicating HPLC method was developed and validated for the
      quantitative determination of orlistat in capsule dosage forms. An isocratic
      separation was achieved using a Perfectsil target ODS-3, 250 mm x 4.6 mm i.d., 5
      microm particle size column with a flow rate of 0.7 ml/min and using a UV
      detector to monitor the eluate at 210 nm. The mobile phase consisted of
      methanol:acetonitrile:trifluoroacetic acid (82.5:17.5:0.01, v/v/v). The drug was
      subjected oxidation, hydrolysis, photolysis and heat to apply stress conditions.
      Complete separation was achieved for the parent compound and all degradation
      products in an overall analytical run time of approximately 15 min with the
      parent compound orlistat eluting at approximately 9 min. The method was linear
      over the concentration range of 0.02-0.75 mg/ml (r = 0.9998) with a limit of
      detection and quantitation 0.006 and 0.02 mg/ml, respectively. The method has the
      requisite accuracy, selectivity, sensitivity and precision to assay orlistat in
      capsules. Degradation products resulting from the stress studies did not
      interfere with the detection of orlistat and the assay is thus stability
      indicating.

PMID- 16603171
TI  - Determination of DL-tetrahydropalmatine in Corydalis yanhusuo by L
      tetrahydropalmatine imprinted monolithic column coupling with reversed-phase high
      performance liquid chromatography.
AB  - A method for direct determination of DL-tetrahydropalmatine (DL-THP) in Corydalis
      yanhusuo, a traditional Chinese herb, by L-THP imprinted monolithic precolumn on
      line/off-line coupling with reversed-phase high performance liquid chromatography
      (RP-HPLC) was developed. The L-THP imprinted monolithic column has been prepared
      by in situ polymerization using methacrylic acid (MAA) and ethylene
      dimethacrylate (EDMA) as functional monomer and cross-linker, respectively. With
      the optimization of chromatographic conditions, such as mobile phase composition,
      flow rate, column temperature and sample loading, for the separation of
      enantiomer, DL-THP was base-line separated on the MIP. The imprinted monolithic
      column was used as a precolumn for fractionation of the C. yanhusuo extract. Both
      the non-retained and retained fractions were separated by RP-HPLC. Meanwhile, the
      D-THP and L-THP can be detected in the non-retained and retained fractions,
      respectively. Additionally, direct determination of L-THP using molecularly
      imprinted monolith on-line coupling with a reversed-phase column was acquired.

PMID- 16603172
TI  - Removal of arsenious ion by calcined aluminum oxyhydroxide (boehmite).
AB  - Aluminum oxyhydroxide (boehmite, BE) shows adsorption ability of arsenious ion.
      In this study, we calcined BE in the temperature range 200-1150 degrees C, and
      examined the amount of arsenious ion adsorbed and adsorption mechanism. As a
      result, the adsorption amount of arsenious ion by BE calcined at 400 degrees C
      showed the highest value as compared with those by BE calcined at other
      temperatures. On the other hand, the amounts of arsenious ion adsorbed onto BE
      showed lower values at 200, 600, and >1000 degrees C than that by BE before
      calcination. The amount of surface hydroxyl group of calcined BE showed the
      highest value at the calcination temperature of 400 degrees C. As a result of X
      ray analysis, BE showed boehmite structure at less than the calcination
      temperature of 300 degrees C, while BE was converted to the transitional state of
      aluminum oxide at more than 400 degrees C. From the result of the amount of
      arsenious ion adsorbed and FT-IR, it turned out that calcined BE dissociated
      water molecule when suspended in the water, hydroxyl group was generated on the
      surface, and the amount of arsenious ion adsorbed was increased because of the
      ion exchange of these hydroxyl groups with arsenious ions. It was clarified that
      an adsorbent with high adsorption ability of arsenious ion was obtained by
      calcination of BE.

PMID- 16603173
TI  - Flux stabilization of silicon nitride microsieves by backpulsing and surface
      modification with PEG moieties.
AB  - The influence of the surface properties of chemically modified silicon nitride
      microsieves on the filtration of protein solutions and defatted milk is described
      in this research. Prior to membrane filtrations, an antifouling polymer based on
      poly(ethylene glycol), poly(TMSMA-r-PEGMA) was synthesized and applied on silicon
      based surfaces like silicon, silicon nitride, and glass. The ability of such
      coating to repel proteins like bovine serum albumin (BSA) was confirmed by
      ellipsometry and confocal fluorescence microscopy. In BSA and skimmed milk
      filtrations no differences could be seen between unmodified and PEG-coated
      membranes (decreasing permeability in time). On the other hand, reduced fouling
      was observed with PEG-modified microsieves in combination with backpulsing and
      air sparging.

PMID- 16603174
TI  - Model for Plateau border drainage of power-law fluid with mobile interface and
      its application to foam drainage.
AB  - A model for drainage of a power-law fluid through a Plateau border is proposed
      which accounts for the actual Plateau border geometry and interfacial mobility.
      The non-dimensionalized Navier-Stokes equations have been solved using finite
      element method to obtain the contours of velocity within the Plateau border cross
      section and average Plateau border velocity in terms of dimensionless inverse
      surface viscosity and power-law rheological parameters. The velocity coefficient,
      the correction for the average velocity through a Plateau border of actual
      geometry compared to that for a simplified circular geometry of the same area of
      cross section, was expressed as a function of dimensionless inverse surface
      viscosity and flow behavior index of the power-law fluid. The results of this
      improved model for Plateau border drainage were then incorporated in a previously
      developed foam drainage model [G. Narsimhan, J. Food Eng. 14 (1991) 139] to
      predict the evolution of liquid holdup profiles in a standing foam. Foam drainage
      was found to be slower for actual Plateau border cross section compared to
      circular geometry and faster for higher interfacial mobility and larger bubble
      size. Evolution of liquid holdup profiles in a standing foam formed by whipping
      and stabilized by 0.1% beta-lactoglobulin in the presence of xanthan gum when
      subjected to 16g and 45g centrifugal force fields was measured using magnetic
      resonance imaging for different xanthan gum concentrations. Drainage resulted in
      the formation of a separate liquid layer at the bottom at longer times. Measured
      bubble size, surface shear viscosity of beta-lactoglobulin solutions and
      literature values of power-law parameters of xanthan gum solution were employed
      in the current model to predict the evolution of liquid holdup profile which
      compared well with the experimental data. Newtonian model for foam drainage for
      zero shear viscosity underpredicted drainage rates and did not agree with the
      experimental data.

PMID- 16603175
TI  - Facile size-regulated synthesis of silver nanoparticles by controlled thermolysis
      of silver alkylcarboxylates in the presence of alkylamines with different chain
      lengths.
AB  - Controlled thermolysis of silver alkylcarboxylates with primary alkylamines was
      investigated as a facile synthetic method of silver nanoparticles. A series of
      silver alkylcarboxylates, C(7)H(15)COOAg, C(13)H(27)COOAg, and C(17)H(35)COOAg,
      have been prepared and the thermolysis of those silver alkylcarboxylates in the
      presence of various alkylamines, C(8)H(17)NH(2), C(12)H(25)NH(2), and
      C(18)H(37)NH(2), with no use of solvent was conducted at 120 or 180 degrees C for
      5 h, providing spherical silver nanoparticles stabilized by alkylcarboxylates and
      alkylamines. The size and dispersibility of nanoparticles depend on the alkyl
      chain length of the precursors, alkylcarboxylates and alkylamines.

PMID- 16603176
TI  - Electroosmotically enhanced mass transfer through polyacrylamide gels.
AB  - We present an internal pumping strategy to enhance solute fluxes in polymer gels.
      The method is based on electroosmotic flow driven by an electric field applied
      across a gel that has been doped with charged colloidal inclusions. This work is
      motivated by the need to enhance the transport in gel-based biosensor devices
      whose response dynamics are often mass transfer limited. In this case,
      polyacrylamide gel slabs were doped with immobilized, charged silica colloids,
      and the flux of a fluorescent tracer was measured as a function of applied field
      strength, the volume fraction and size of the colloidal silica inclusions, and
      the bulk electrolyte composition. Significant flux enhancements were achieved
      with applied electric currents on the order of a few mA. Control experiments
      indicated that the flux enhancement was not due to any distortion of the gel
      diffusional properties in response to the presence of the inclusions. At a
      constant inclusion volume fraction, the electroosmotic solute flux enhancement
      was strongest for the smallest particle sizes that provide the highest total
      surface area, consistent with the electroosmotic mechanism whereby fluid flow is
      generated along the solid/liquid interface.

PMID- 16603177
TI  - Effects of cholesterol component on molecular interactions between paclitaxel and
      phospholipid within the lipid monolayer at the air-water interface.
AB  - Cholesterol is a main component of the cell membrane and could have significant
      effects on drug-cell membrane interactions and thus the therapeutic efficacy of
      the drug. It also plays an important role in liposomal formulation of drugs for
      controlled and targeted delivery. In this research, Langmuir film technique,
      atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR)
      are employed for a systematic investigation on the effects of cholesterol
      component on the molecular interactions between a prototype antineoplastic drug
      (paclitaxel) and 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) within the
      cell membrane by using the lipid monolayer at the air-water interface as a model
      of the lipid bilayer membrane and the biological cell membrane. Analysis of the
      measured surface pressure (pi) versus molecular area (a) isotherms of the mixed
      DPPC/paclitaxel/cholesterol monolayers at various molar ratios shows that DPPC,
      paclitaxel and cholesterol can form a non-ideal miscible system at the air-water
      interface. Cholesterol enhances the intermolecular forces between paclitaxel and
      DPPC, produces an area-condensing effect and thus makes the mixed monolayer more
      stable. Investigation of paclitaxel penetration into the mixed DPPC/cholesterol
      monolayer shows that the existence of cholesterol in the DPPC monolayer can
      considerably restrict the drug penetration into the monolayer, which may have
      clinical significance for diseases of high cholesterol. FTIR and AFM
      investigation on the mixed monolayer deposited on solid surface confirmed the
      obtained results.

PMID- 16603178
TI  - Reflections on how color term acquisition is constrained.
AB  - Compared with object word learning, young children typically find learning color
      terms to be a difficult linguistic task. In this reflections article, I consider
      two questions that are fundamental to investigations into the developmental
      acquisition of color terms. First, I consider what constrains color term
      acquisition and how stable these constraints are over culture and age. I review
      recent studies that have identified conceptual, attentional, and linguistic
      constraints that seemingly operate on the acquisition of color terms compared
      with object words and the differential acquisition of color terms within a given
      language. Second, I consider whether these constraints are specific to the
      acquisition of color terms or whether they reflect more general constraints that
      operate on other classes of lexical terms such as different abstract property
      terms.

PMID- 16603179
TI  - Effective gene suppression using small interfering RNA in hard-to-transfect human
      T cells.
AB  - RNA interference (RNAi) is an evolutionarily conserved cellular defense mechanism
      that protects cells from hostile genes and regulates the function of normal genes
      during growth and development. In this study, we established proof of principle
      of small interfering RNA (siRNA) silencing in hard-to-transfect human T cell
      lines and primary human CD4 T cells. We used public and in-house programs to
      design four siRNAs each for GFP, for our novel cellular gene HALP, and for their
      corresponding scrambled siRNA controls. We generated siRNA expression cassettes
      (SECs) by PCR and directly transfected the PCR products into T cells using amaxa
      Nucleofector technology. The most effective SECs were selected and cloned into a
      TA cloning vector and titered with their respective controls to increase
      transfection efficiency. Flow cytometry and fluorescence microscopy analyses were
      performed for GFP siRNAs, and Northern blot analysis was done to assess the HALP
      silencing effect. These experiments demonstrate that SECs are an excellent
      screening tool to identify siRNA sequences effective in silencing expression of
      genes of interest. The vector expressing the most effective siRNA robustly
      inhibited GFP expression (up to 92%) in the context of co-transfection in human T
      cell lines and primary CD4 T cells. The optimized siRNA for our endogenous
      cellular gene HALP also silenced its target RNA expression by more than 90%.
      These studies demonstrate that the combination of SEC, siRNA expression vectors
      and Nucleofector technology can be successfully applied to hard-to-transfect
      human T cell lines and primary T cells to effectively silence genes.

PMID- 16603180
TI  - Functional display of Bacillus thuringiensis Cry1Ac toxin on T7 phage.
AB  - The Cry1Ac toxin from Bacillus thuringiensis was displayed on the surface of T7
      phage. The cry1Ac gene was fused to the C-terminal end of T7-10B capsid protein
      and displayed on the surface of T7 phage as revealed by Western blot analysis of
      the purified phage particles. The T7-Cry1Ac phages retained toxicity against
      Manduca sexta larvae. We demonstrated that the T7-Cry1Ac phage interacts with
      Cry1Ac receptors present in M. sexta BBMV either in solution or in overlay
      binding assays.

PMID- 16603181
TI  - Anti-adrenergic effects of endothelin on human atrial action potentials are
      potentially anti-arrhythmic.
AB  - Endothelin-1 (ET-1) is elevated in patients with atrial fibrillation (AF) and
      heart failure. We investigated effects of ET-1 on human atrial cellular
      electrophysiological measurements expected to influence the genesis and
      maintenance of AF. Action potential characteristics and L-type Ca(2+) current
      (I(CaL)) were recorded by whole cell patch clamp, in atrial isolated myocytes
      obtained from patients in sinus rhythm. Isoproterenol (ISO) at 0.05 muM prolonged
      the action potential duration at 50% repolarisation (APD(50): 54 +/- 10 vs. 28 +/
      5 ms; P < 0.05, N = 15 cells, 10 patients), but neither late repolarisation nor
      cellular effective refractory period (ERP) were affected. ET-1 (10 nM) reversed
      the effect of ISO on APD(50), and had no basal effect (in the absence of ISO) on
      repolarisation or ERP. During repetitive stimulation, ISO (0.05 microM) produced
      arrhythmic depolarisations (P < 0.05). Each was abolished by ET-1 at 10 nM (P <
      0.05). ISO (0.05 microM) increased peak I(CaL) from -5.5 +/- 0.4 to -14.6 +/- 0.9
      pA/pF (P < 0.05; N = 79 cells, 34 patients). ET-1 (10 nM) reversed this effect by
      98 +/- 10% (P < 0.05), with no effect on basal I(CaL). Chronic treatment of
      patients with a beta-blocker did not significantly alter basal APD(50) or I(CaL),
      the increase in APD(50) or I(CaL) by 0.05 microM ISO, nor the subsequent reversal
      of this effect on APD(50) by 10 nM ET-1. The marked anti-adrenergic effects of ET
      1 on human atrial cellular action potential plateau, arrhythmic depolarisations
      and I(CaL), without affecting ERP and independently of beta-blocker treatment,
      may be expected to contribute a potentially anti-arrhythmic influence in the
      atria of patients with AF and heart failure.

PMID- 16603182
TI  - Erythroid cells play essential roles in angiogenesis by bone marrow cell
      implantation.
AB  - Bone marrow cell implantation (BMI) has been utilized to treat patients with limb
      and heart ischemia. BMI provides angiogenic precursors and angiogenic cytokine
      producing cells, especially erythroid cells. In this study, we induced in vitro
      angiogenesis cultures and in vivo BMI simulation using a murine limb ischemia
      model to examine the role of erythroid cells and the effect of erythropoietin
      (EPO). Human erythroid colonies (BFU-e) induced capillary networks around the
      colonies in vitro. Erythroid cells in human bone marrow produced vascular
      endothelial growth factor and placental growth factor. The angiogenic effects of
      erythroid cells were further amplified in the presence of EPO. Limb-ischemic mice
      were treated with BMI +/- EPO, and limb survival, blood flow recovery, and muscle
      histology were analyzed. Treatment with whole bone marrow cells + EPO
      significantly improved limb survival and blood flow. The cumulative effects of
      EPO on BMI induced and increase in capillary number and artery enlargement.
      Erythroid cells were essential for the in vivo effects of BMI, and CD14-positive
      cells supported the biological effects. In addition to the direct effect of EPO
      on angiogenesis, EPO showed indirect effect on angiogenesis through amplifying
      the angiogenic effects by erythroid cells supported by CD14-positive cells.

PMID- 16603183
TI  - Combining pharmacological mobilization with intramyocardial delivery of bone
      marrow cells over-expressing VEGF is more effective for cardiac repair.
AB  - We postulated that combining cell based hVEGF165 gene delivery with cytokine
      induced mobilization of bone marrow cells (BMC) may give better prognosis in an
      infarcted heart. Forty-eight myoabalated female C57BL/6J mice (20-25 g) received
      1 x 10(6) BMC from transgenic GFP+ male mice. One month later, acute myocardial
      infarction (MI) model was developed by coronary artery ligation. Animals were
      grouped (N = 12) to receive intramyocardial injections of 10 microl DMEM without
      cells (group 1; group 2) or with 1x10(5) mesenchymal stem cells (MSC) over
      expressing hVEGF165 (group 3; group 4). The animals received either cytokine
      therapy (group 2 and 4) or saline solution (group 1 and 3) for 7 days after MI.
      Hemodynamic data were obtained 4 weeks after MI using Millar's P-V system and
      cardiac tissue was harvested for immunohistological studies. We observed
      regeneration and extensive survival of BMC in and around the infarcted myocardium
      in groups 3 and 4. Blood vessel density was markedly enhanced in group 4 as
      compared with groups 1 and 2 in peri-infarct area. Fibrotic area was
      significantly reduced with improved LV-contractile function in group 2 and 4. LV
      systolic and diastolic functions were well-preserved in group 4 as indicated by
      +dP/dt, -dP/dt and Tau (glantz). We therefore conclude that transplantation of
      MSC overexpressing VEGF combined with cytokine induced BMC mobilization is
      superior to either of the monotherapy approach for angiomyogenesis and LV
      function recovery.

PMID- 16603184
TI  - Blockade of histamine H2 receptors protects the heart against ischemia and
      reperfusion injury in dogs.
AB  - We have previously reported that histamine H(2) blockers may be cardioprotective
      in patients with chronic heart failure. Since both endogenous histamine and
      histamine H(2) receptors are present in heart tissue, we tested the hypothesis
      that the blockade of histamine H(2) receptors mediates protection against
      reversible or irreversible ischemia and reperfusion injury. In open-chest dogs,
      the left anterior descending coronary artery was occluded for 90 minutes,
      followed by reperfusion for 6 hours. Administration of famotidine and cimetidine
      from 10 minutes before occlusion until after 1 hour of reperfusion reduced
      infarct size (17.0 +/- 4.1% and 17.8 +/- 2.9% vs. 36.9 +/- 5.9% of the solvent
      group, respectively) Famotidine administration only during the reperfusion period
      for 1 hour also attenuated infarct size (22.5 +/- 3.5%). There were no
      differences in either area at risk or collateral flow among the groups. In
      another set of experiments, we decreased coronary perfusion pressure in dogs so
      that the coronary blood flow decreased to 50% of the non-ischemic level. In such
      conditions, we observed the increases in histamine release compared with non
      ischemic conditions (0.04 +/- 0.03 to 0.28 +/- 0.13 ng/ml, p < 0.05). Famotidine
      improved anaerobic myocardial metabolism gauged by both lactate extraction ratio
      and myocardial oxygen consumption. We conclude that the blockade of histamine
      H(2) receptors mediates improvements in the anaerobic myocardial metabolism, and
      thus protects against ischemia and reperfusion injury.

PMID- 16603185
TI  - Characterization of intra-molecular distances and site-specific dynamics in
      chemically unfolded barstar: evidence for denaturant-dependent non-random
      structure.
AB  - The structure and dynamics of the unfolded form of a protein are expected to play
      critical roles in determining folding pathways. In this study, the urea and
      guanidine hydrochloride (GdnHCl)-unfolded forms of the small protein barstar were
      explored by time-resolved fluorescence techniques. Barstar was labeled
      specifically with thionitrobenzoate (TNB), by coupling it to the thiol side-chain
      of a cysteine residue at one of the following positions on the sequence: 14, 25,
      40, 42, 62, 82 and 89, in single cysteine-containing mutant proteins. Seven intra
      molecular distances (R(DA)) under unfolding conditions were estimated from
      measurements of time-resolved fluorescence resonance energy transfer between the
      donor Trp53 and the non-fluorescent acceptor TNB coupled to one of the seven
      cysteine side-chains. The unfolded protein chain expands with an increase in the
      concentration of the denaturants. The extent of expansion was found to be non
      uniform, with different intra-molecular distances expanding to different extents.
      In general, shorter distances were found to expand less when compared to longer
      spans. The extent of expansion was higher in the case of GdnHCl when compared to
      urea. A comparison of the measured values of R(DA) with those derived from a
      model based on excluded volume, revealed that while shorter spans showed good
      agreement, the experimental values of R(DA) of longer spans were smaller when
      compared to the theoretical values. Sequence-specific flexibility of the
      polypeptide was determined by time-resolved fluorescence anisotropy decay
      measurements on acrylodan or 1,5-IAEDANS labeled single cysteine-containing
      proteins under unfolding conditions. Rotational dynamics derived from these
      measurements indicated that the level of flexibility increased with increase in
      the concentration of denaturants and showed a graded increase towards the C
      terminal end. Taken together, these results appear to indicate the presence of
      specific non-random coil structures and show that the deviation from random coil
      structure is different for the two denaturants.

PMID- 16603186
TI  - Structural insights of the specificity and catalysis of a viral histone H3 lysine
      27 methyltransferase.
AB  - SET domain lysine methyltransferases are known to catalyze site and state
      specific methylation of lysine residues in histones that is fundamental in
      epigenetic regulation of gene activation and silencing in eukaryotic organisms.
      Here we report the three-dimensional solution structure of the SET domain histone
      lysine methyltransferase (vSET) from Paramecium bursaria chlorella virus 1 bound
      to cofactor S-adenosyl-L-homocysteine and a histone H3 peptide containing mono
      methylated lysine 27. The dimeric structure, mimicking an
      enzyme/cofactor/substrate complex, yields the structural basis of the substrate
      specificity and methylation multiplicity of the enzyme. Our results from
      mutagenesis and enzyme kinetics analyses argue that a general base mechanism is
      less likely for lysine methylation by SET domains; and that the only invariant
      active site residue tyrosine 105 in vSET facilitates methyl transfer from
      cofactor to the substrate lysine by aligning intermolecular interactions in the
      lysine access channel of the enzyme.

PMID- 16603187
TI  - Breakdown of intestinal mucosa via accelerated apoptosis increases intestinal
      permeability in experimental severe acute pancreatitis.
AB  - BACKGROUND: Bacterial translocation plays an important role for infectious
      complications in severe acute pancreatitis (SAP). Breakdown of intestinal mucosal
      integrity may increase intestinal permeability and may be implicated in bacterial
      translocation. It is suggested that increase in intestinal permeability is
      correlated with the changes of tight junction and/or apoptosis in intestinal
      epithelial cells. The aim of this study was to investigate the changes of
      intestinal mucosa and its permeability in SAP. METHODS: SAP was induced by
      injection of 3% sodium deoxycholate into the biliopancreatic ducts in rats.
      Permeability of intestinal wall was assayed ex vivo by measuring the leaked
      amount of FITC-dextran from the ileum pouch. Alteration of tight junction
      proteins such as zonula occludens (ZO)-1 and Occludin was evaluated by Western
      blotting and immunofluorescence staining. Apoptotic change of intestinal mucosa
      was detected by TUNEL staining and DNA fragmentation ELISA. In vitro, apoptosis
      inducing effect of pancreatitis-associated ascitic fluid (PAAF) was examined
      using T84 cells. Integrity of monolayer cells was assessed by transepithelial
      electric resistance (TEER). RESULTS: Permeability of ileum was significantly
      increased 6 h after induction of SAP. Blood endotoxin level was significantly
      elevated and bacterial translocation occurred 18 h after induction of SAP. Six
      hours after induction of SAP, expressions of ZO-1 and Occludin were not altered,
      but apoptosis of ileum mucosa was significantly accelerated. Addition of PAAF to
      T84 cells did not affect expressions of ZO-1 or Occludin, but significantly
      increased the apoptosis and significantly decreased TEER. CONCLUSIONS: These
      results suggest that breakdown of intestinal mucosa via accelerated apoptosis may
      increase in intestinal permeability in SAP and that PAAF contains factor(s) that
      accelerates the apoptosis of intestinal epithelial cells.

PMID- 16603188
TI  - Development of a human cardiac tissue-based angiogenesis model.
AB  - BACKGROUND: Previous angiogenesis models use animal tissues such as the chicken
      chorioallantoic membrane (CAM) or the rabbit cornea. These models may not
      accurately reflect the mechanisms responsible for human angiogenesis. MATERIALS
      AND METHODS: We hypothesized that fragments of human myocardial tissue would
      develop an angiogenic response from the cut edges of vessels contained within the
      tissue. To test these hypotheses, we obtained human atrial appendage tissue at
      the time of cardiac bypass. Fragments of atrial tissue were then incorporated
      into fibrin thrombin clots. Tissue fragments were observed, and the percent of
      wells that developed neovessel invasion into the clot was calculated (%I). The
      subsequent growth of cardiac-derived microvessels was rated and scored over time
      (Angiogenic Index). RESULTS: There were 20 human atrial appendages plated (n = 24
      to 60 wells/specimen) and evaluated in this model. Out of the 20, 16 (80%) atrial
      appendages developed an angiogenic response in the majority (>50%) of wells
      plated. Neovessel growth was progressive over 14 to 16 days in culture in all
      specimens tested. The mean angiogenic index of all specimens was 8.59 +/- 0.91.
      CONCLUSIONS: This human cardiac tissue-based assay might be useful to screen
      compounds designed for use in human trials or provide highly vascularized cardiac
      tissue for autotransplantation. Additionally, the assay provides the foundation
      to study an individual patent's cardiac tissue and its response to angiogenesis
      stimulators or inhibitors. This may allow the development of patient-specific
      therapies designed to enhance revascularization or repair of injured cardiac
      muscle.

PMID- 16603189
TI  - A prospective evaluation of novel methods to intraoperatively distinguish
      parathyroid tissue utilizing a parathyroid hormone assay.
AB  - BACKGROUND: Frozen section analysis has traditionally been used to confirm the
      identity of parathyroid tissue intraoperatively; however, it is time-consuming
      and costly and requires the excision of a significant portion of tissue. An
      intraoperative biopsy and analysis with a parathyroid hormone (PTH) assay is a
      possible alternative; however, this technique has not been perfected. METHODS:
      Two hundred twenty-three tissue specimens were collected prospectively from
      patients undergoing neck exploration. Each specimen was sampled intraoperatively
      using three different biopsy techniques: a fine-needle aspiration (FNA) with 10
      passes of a needle (FNA10), a FNA with 20 passes of a needle (FNA20), and a
      tissue biopsy of approximately 1.0 mm3 (BIOPSY). The PTH concentration of each
      sample was determined via the Elecsys 1010 PTH immunoassay. The final tissue
      diagnosis was determined by histology or operative data. RESULTS: Parathyroid
      samples from all techniques had higher median PTH concentrations than
      nonparathyroid samples. However, the accuracies for the detection of parathyroid
      tissue varied markedly (PTH cutoff of 1000 pg/ml): the accuracies of the FNA10
      and FNA20 were 71 and 80%, respectively, while the BIOPSY was 99% accurate.
      CONCLUSIONS: This is the first prospective study evaluating multiple methods to
      diagnose parathyroid tissue intraoperatively using a rapid PTH assay. We
      conclusively show that the BIOPSY technique is 99% accurate for the diagnosis of
      parathyroid tissue, and therefore, should be the method of choice when the
      intraoperative confirmation of parathyroid tissue is needed.

PMID- 16603190
TI  - ZM336372, a Raf-1 activator, inhibits growth of pheochromocytoma cells.
AB  - BACKGROUND: Surgical resection is the only curative treatment for patients with
      pheochromocytomas, paragangliomas, and other catecholamine-producing tumors.
      Patients with metastatic disease can often have significant symptoms associated
      with catecholamine excess. Activation of the Raf-1/MEK/ERK1/2 pathway has been
      shown to inhibit growth and hormone production for neuroendocrine tumors (NE)
      such as carcinoid and medullary thyroid cancer. However, the role of the Raf
      1/MEK/ERK1/2 signaling pathway in pheochromocytomas is unknown. MATERIALS AND
      METHODS: Pheochromocytoma PC-12 cells were treated with varying concentrations of
      ZM336372, a pharmacologic Raf-1 activating drug. Levels of phosphorylated ERK1/2
      and the NE marker Chromogranin A (CgA) were determined by Western blot. Cellular
      growth was measured by MTT cell-proliferation assay. RESULTS: At baseline, PC-12
      cells had very little phosphorylated ERK1/2, similar to other NE tumors.
      Treatment of PC-12 cells with increasing dosages of ZM336372 resulted in
      increased phosphorylated ERK1/2. Importantly, ZM336372 inhibited pheochromocytoma
      cellular proliferation. Furthermore, Raf-1 pathway activation by ZM336372 was
      associated with suppression of NE marker, CgA, by the tumor cells. CONCLUSIONS:
      These data suggest that Raf-1/MEK/ERK1/2 pathway activation may be a novel
      strategy to treat pheochromocytoma and other catecholamine-producing tumors. In
      pheochromocytoma cells, ZM336372 blocks cellular proliferation and suppresses NE
      vasoactive peptide production. Thus, ZM336372 may be used for both therapeutic
      and palliative treatment for patients with pheochromocytomas.

PMID- 16603191
TI  - Angiogenic profile of soft tissue sarcomas based on analysis of circulating
      factors and microarray gene expression.
AB  - BACKGROUND: Broader understanding of diverse angiogenic pathways in a particular
      cancer can lead to better utilization of anti-angiogenic therapies. The aim of
      this study was to develop profiles of angiogenesis-related gene and protein
      expression for various histologic subtypes of soft tissue sarcomas (STS) growing
      in different sites. MATERIALS AND METHODS: Plasma levels of vascular endothelial
      growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin 2
      (Ang2), and leptin were determined in 108 patients with primary STS. Gene
      expression patterns were analyzed in 38 STS samples and 13 normal tissues using
      oligonucleotide microarrays. RESULTS: VEGF and bFGF plasma levels were elevated
      10-13 fold in STS patients compared to controls. VEGF levels were broadly
      elevated while bFGF levels were higher in patients with fibrosarcomas and
      leiomyosarcomas. Ang2 levels correlated with tumor size and were most elevated
      for tumors located in the trunk, while leptin levels were highest in patients
      with liposarcomas. Hierarchical clustering of microarray data based on
      angiogenesis-related gene expression demonstrated that histologic subtypes of STS
      often shared similar expression patterns, and these patterns were distinctly
      different from those of normal tissues. Matrix metalloproteinase 2, platelet
      derived growth factor receptor, alpha and Notch 4 were among several genes that
      were up-regulated at least 7-fold in STS. CONCLUSIONS: STS demonstrate
      significant heterogeneity in their angiogenic profiles based on size, histologic
      subtype, and location of tumor growth, which may have implications for anti
      angiogenic strategies. Comparison of STS to normal tissues reveals a panel of
      upregulated genes that may be targets for future therapies.

PMID- 16603192
TI  - Panic disorder or epilepsy? A case report.
AB  - Psychiatric and neurological disturbances can show up with panic attack symptoms.
      This report illustrates the difficulty in distinguishing between panic disorder
      and epilepsy in a subgroup of epileptic patients that suffer panic attacks as
      symptoms of seizures. This is the first report of panic attacks due to a focal
      lesion involving the left temporal lobe and the second case of panic attacks
      related to a meningioma.

PMID- 16603193
TI  - Optimization of semi-quantification in metabolic PET studies with 18F
      fluorodeoxyglucose and 11C-methionine in the determination of malignancy of
      gliomas.
AB  - The treatment of the glioma patient depends on the nature of the lesion and on
      the aggressiveness of the tumor. The management of gliomas continues to be a
      challenging task, because morphological neuroimaging techniques do not always
      differentiate them from nontumoral lesions or high grade tumors from low grade
      lesions. Positron Emission Tomography (PET) offers the possibility of the in vivo
      quantitative characterization of brain tumors. Despite decades of useful
      application of PET in the clinical monitoring of gliomas, no consensus has been
      reached on the most effective image analysis approach for providing the best
      diagnostic performance under heavy-duty clinical diagnostic circumstances. The
      main objective of the present study was to find and validate optimal semi
      quantitative search strategies for metabolic PET studies on gliomas, with special
      regard to the optimization of those metabolic tracer uptake ratios most sensitive
      in predicting histologic grade and prognosis. 11C-Methionine (11C-Met, n = 50)
      and/or 18F-Fluorodeoxyglucose (18F-FDG, n = 33) PET measurements were performed
      in 59 patients with primary and recurrent brain gliomas (22 high grade and 37 low
      grade tumors) in order to correlate the biological behavior and 11C-Met/18F-FDG
      uptake of tumors. Data were analyzed by region-of-interests (ROI) methods using
      standard uptake value calculation. Different ROI defining strategies were then
      compared with each other for two of the most commonly used metabolic
      radiotracers, 18F-FDG and 11C-Met, in order to determine their usefulness in
      grading gliomas. The results were compared to histological data in all patients.
      Both ANOVA and receiver operating characteristic (ROC) analysis indicated that
      the performance of 18F-FDG was superior to that of 11C-Met for most of the
      ratios. 18F-FDG is therefore suggested as the tracer of choice for noninvasive
      semi-quantitative indicator of histologic grade of gliomas. 11C-Methionine has
      been suggested as a complimentary tracer, useful in delineating the extent of the
      tumor. The best diagnostic performance was obtained by calculating the ratio of
      the peak 18F-FDG uptake of the tumor to that of white matter (p < 0.001; ANOVA).
      This metabolic tracer uptake ratio is therefore suggested as an easily obtained
      semi-quantitative PET indicator of malignancy and histological grade in gliomas.

PMID- 16603194
TI  - Biological models: measuring variability with classical and quantum information.
AB  - This essay proposes methods to analyse the variability of biological data. The
      idea is to express the state of a biological system as a linear combination of
      base states in a Hilbert space. Coefficients of the linear combination can be
      interpreted as probabilities and informational entropy is associated to each
      state allowing the definition of a classical variability measure. Besides, state
      transition matrices can also be calculated and their norms express the dynamics
      of the system organization and a quantum variability measure. As the examples
      show, the classical measure expresses a structural variability and the quantum
      measure expresses a functional variability.

PMID- 16603195
TI  - The recognition and prediction of sigma70 promoters in Escherichia coli K-12.
AB  - Based on the conservation analysis of the 683 latest experimentally verified
      sigma(70)-promoter sequences of Escherichia coli K-12, it is found that the
      conservative hexamers segments in different sites play a key role of promoter
      regions, a novel position-correlation scoring matrix (PCSM) algorithm for
      predicting sigma(70) promoter is presented. The predictive capacity of the
      algorithm is tested by 10-cross validation test. The results show that the
      overall prediction accuracies (sensitivity) and specificity are 91% and 81%,
      respectively. By selecting the 683 experimentally verified sigma(70) promoters as
      training set and searching for the complete sequence in E. coli K-12 with
      4639221bp. Results show that the 100% of the 683 experimentally verified
      sigma(70) promoters have been identified and some possible promoters are
      predicted.

PMID- 16603196
TI  - Periodic oscillations in leukopoiesis models with two delays.
AB  - The term leukopoiesis describes processes leading to the production and
      regulation of white blood cells. It is based on stem cells differentiation and
      may exhibit abnormalities resulting in severe diseases, such as cyclical
      neutropenia and leukemias. We consider a nonlinear system of two equations,
      describing the evolution of a stem cell population and the resulting white blood
      cell population. Two delays appear in this model to describe the cell cycle
      duration of the stem cell population and the time required to produce white blood
      cells. We establish sufficient conditions for the asymptotic stability of the
      unique nontrivial positive steady state of the model by analysing roots of a
      second degree exponential polynomial characteristic equation with delay-dependent
      coefficients. We also prove the existence of a Hopf bifurcation which leads to
      periodic solutions. Numerical simulations of the model with parameter values
      reported in the literature demonstrate that periodic oscillations (with short and
      long periods) agree with observations of cyclical neutropenia in patients.

PMID- 16603197
TI  - Application of rigid body mechanics to theoretical description of rotation within
      F0F1-ATP synthase.
AB  - ATP synthase catalyses the formation of ATP from ADP and P(i) and is powered by
      the diffusion of protons throughout membranes down the proton electrochemical
      gradient. The protein consists of a water-soluble F(1) and a transmembrane F(0)
      proton transporter part. It was previously shown that the ring of membrane
      subunits rotates past a fixed subunit during catalytic cycle of the enzyme.
      However, many parameters of this movement are still unknown. In the present study
      the mutual protein movement in the membrane part of F(0)F(1)-ATP syntase has been
      analysed within the framework of rigid body mechanics. On the base of available
      experimental data it was shown that electrostatic interaction of two charged
      amino acids residues is able to supply quite enough energy for the rotation. The
      initial torque, which caused the rotation, was estimated as 3.7 pN nm and for
      this pattern the angular movement of c subunits complex could not physically have
      a period less than 10(-9)s. If membrane viscosity and elastic resistance were
      taken into account then the time of a whole turnover could rise up to 6.3 x 10(
      3)s. It is remarkable that rotation will take place only under condition when the
      elasticity (Young's) module of the central stalk (gamma subunit and other minor
      subunits) is less than 5.0 x 10(7)N/m(2). Thus, for generally accepted structural
      parameters of ATP synthase, two-charge electrostatic interaction model does not
      permit rotation of the rotor if elastic properties of the central stalk are
      tougher than mentioned above. In order to explain the rotation under that
      condition one should either suppose a shorter distance between subunit a and c
      subunits complex or assume interaction of more than two charged amino acids
      residues.

PMID- 16603198
TI  - A selective beta2-adrenergic agonist, terbutaline, improves sepsis-induced
      diaphragmatic dysfunction in the rat.
AB  - BACKGROUND: Sepsis causes diaphragmatic dysfunction, which can lead to the
      development of respiratory failure. We previously reported that isoproterenol,
      non-selective beta-adrenergic agonist, improved contractility of the diaphragm in
      a septic rat model. Since beta(2)-adrenoceptor agonists are widely used in the
      treatment of chronic respiratory disease, we investigated the effect of
      terbutaline, a selective beta(2)-adrenergic agonist, on contractility of the
      septic rat diaphragm and the contribution of intracellular Ca(2+) to the effect
      of terbutaline in vitro. METHODS: Forty-eight rats were divided into a sham group
      (in which sham laparotomy was performed) and a CLP group (in which peritonitis
      was induced by cecal ligation and perforation). The left hemidiaphragm was
      removed at 16 h after the operation. The effect of terbutaline (10(-)(6) M) on
      contractility of the diaphragm was assessed by twitch characteristics (twitch
      tension, contraction time and contraction velocity) and force-frequency
      relationship. In addition, to investigate the role of calcium ions in the effect
      of terbutaline on contractility of the diaphragm, contractility of the diaphragm
      was assessed after the pre-incubation of the diaphragm with methoxy-verapamil
      (10(-)(5) M), Ca(2+)-free Krebs-Ringer's solution buffered with 2 mM of ethylene
      glycol tetra-acetic acid (EGTA), and ryanodine (10(-)(6) M). RESULTS: Terbutaline
      significantly improved twitch characteristics and force-frequency relationship of
      the diaphragm in the CLP group (P<0.01). Incubation with methoxy-verapamil or
      calcium-free solution with EGTA did not show any changes in the inotropic effect
      of terbutaline in the CLP group. However, incubation with ryanodine completely
      abolished the inotropic effect of terbutaline in the CLP group. CONCLUSIONS: The
      present study demonstrated that terbutaline increased contractility of the
      diaphragm in the septic rats. Since this inotropic effect was abolished by
      ryanodine administration, calcium release from the sarcoplasmic reticulum may
      contribute to the terbutaline-induced improvement in dysfunction of the septic
      diaphragm.

PMID- 16603199
TI  - Sennidin stimulates glucose incorporation in rat adipocytes.
AB  - A novel small molecule compound which exerts insulin mimetic is desirable. Dozens
      of natural products that have quinone, naphthoquinone, or anthraquinone
      structure, were tested by a glucose incorporation assay. We found that sennidin
      A, anthraquinone derivative, stimulated glucose incorporation to near level of
      maximal insulin-stimulated and sennidin B, a stereoisomer of sennidin A, also
      stimulated, but the activity of sennidin B was lower than sennidin A. Sennidin A
      stimulated glucose incorporation was completely inhibited by wortmannin. Sennidin
      A did not induce tyrosine phosphorylation of insulin receptor (IR) and insulin
      receptor substrate-1 (IRS-1), but induced phosphorylation of Akt and glucose
      transporter 4 (GLUT4) translocation. Our results suggest that in rat adipocytes,
      sennidin A stimulates glucose incorporation in the phosphatidylinositol 3-kinase
      (PI3K)- and Akt-dependent, but in the IR/IRS1-independent manner.

PMID- 16603200
TI  - Effects of bicyclol on dimethylnitrosamine-induced liver fibrosis in mice and its
      mechanism of action.
AB  - The aim was to investigate the suppressive effect of bicyclol on hepatic fibrosis
      induced by dimethylnitrosamine (DMN) in mice and the mechanism of its action.
      Hepatic fibrosis was established by intraperitoneal injection of 8 mg kg(-1) day(
      1) on three consecutive days of each week for 4 or 5 weeks. In the prophylactic
      experiment, bicyclol (100 and 200mg.kg(-1)) was administered by gavage in
      association with DMN injection. For the therapeutic experiment, mice were firstly
      injected with DMN for 5 weeks as in the prophylactic experiment, and then the
      mice in drug groups were orally administered bicyclol (100 and 200mg.kg(-1)) once
      daily for 5 weeks. As a result, the levels of alanine aminotransferase (ALT),
      total bilirubin, hydroxyproline (Hyp), prolidase, tumor necrosis factor-alpha
      (TNFalpha), transforming growth factor beta-1 (TGFbeta(1)), type I collagen in
      serum and the score of liver fibrosis all significantly increased in the hepatic
      fibrosis model group in comparison with those in control group. The treatment
      with bicyclol markedly reduced all the above criteria. Bicyclol also attenuated
      the decrease of body weight of mice, serum total protein and albumin. In
      addition, bicyclol treatment inhibited liver TGFbeta(1) and tissue inhibitor of
      metalloproteinase 1 (TIMP-1) mRNA expression in the prophylactic experiment.
      Similarly, bicyclol reduced TIMP-1 levels in liver and serum and increased
      collagenase activity in the liver in the therapeutic experiment. The result
      suggest that bicyclol attenuates DMN-induced hepatic fibrosis in mice. Its
      mechanisms of action may be related to the hepatoprotective and anti-inflammation
      properties, the down-regulation of liver TGFbeta(1) and TIMP-1 expression and the
      increase of net collagenase activity in liver.

PMID- 16603201
TI  - The BEEP project in the Baltic Sea: overview of results and outline for a
      regional biological effects monitoring strategy.
AB  - Field studies in the framework of the EU funded BEEP project (Biological Effects
      of Environmental Pollution in Marine Coastal Ecosystems, 2001-2004) aimed at
      validating and intercalibrating a battery of biomarkers of contaminant exposure
      and effects in selected indicator species in the Mediterranean, the North
      Atlantic and the Baltic Seas. Major strategic goals of the BEEP project were the
      development of a sensitive and cost-efficient biological effects monitoring
      approach, delivery of information and advice to end-user groups, and the
      implementation of a network of biomarker researchers around Europe. Based on the
      main results obtained in the Baltic Sea component of the BEEP the present paper
      summarises and assesses the applicability of biomarkers for different regions and
      species in this sea area. Moreover, a general strategy and some practical
      considerations for the monitoring of biological effects in the Baltic Sea are
      outlined.

PMID- 16603202
TI  - Short-term effects of the prestige oil spill on the peregrine falcon (Falco
      peregrinus).
AB  - We have monitored the distribution, population status, breeding success, turnover
      rate and diet of a Peregrine Falcon population in Bizkaia (North of Spain) since
      1997. On the 13th November 2002, the tanker Prestige sunk off La Coruna (NW
      Spain) causing an oil spill that affected the whole of the Cantabrian Coast and
      the Southwest of France. The total number of birds affected by the Prestige oil
      spill was expected to be between 115,000 and 230,000, some of them raptors. The
      loss of clutches during the incubation period increased significantly and was
      correlated with the loss of females. Moreover, the turnover rate of the
      population increased from 21% to 30%. The polycyclic aromatic hydrocarbon
      concentrations in the eggs, collected from five nests after they were deserted,
      ranged from 21.20 ng/g to 461.08 ng/g, values which are high enough to cause the
      death of the embryos and poisoning of adult birds. The effects of pollution
      reached inland since some inland-breeding falcons prey on shorebirds that use
      rivers during their migratory flights. As the Prestige oil spill has clearly
      resulted in increased rates of adult mortality and reduced fertility, we suggest
      that the environmental authorities urgently undertake measures aimed at
      protecting the Peregrine Falcon in Bizkaia.

PMID- 16603203
TI  - Expanding the range of brominated Q1 analogues.

PMID- 16603204
TI  - Comparison of PCBs, organochlorine pesticides, and trace metals in cod liver from
      Georges Bank and Stellwagen Bank, USA and Canada.

PMID- 16603205
TI  - Model identification for DNA sequence-structure relationships.
AB  - We investigate the use of algebraic state-space models for the sequence dependent
      properties of DNA. By considering the DNA sequence as an input signal, rather
      than using an all atom physical model, computational efficiency is achieved. A
      challenge in deriving this type of model is obtaining its structure and
      estimating its parameters. Here we present two candidate model structures for the
      sequence dependent structural property Slide and a method of encoding the models
      so that a recursive least squares algorithm can be applied for parameter
      estimation. These models are based on the assumption that the value of Slide at a
      base-step is determined by the surrounding tetranucleotide sequence. The first
      model takes the four bases individually as inputs and has a median root mean
      square deviation of 0.90 A. The second model takes the four bases pairwise and
      has a median root mean square deviation of 0.88 A. These values indicate that the
      accuracy of these models is within the useful range for structure prediction.
      Performance is comparable to published predictions of a more physically derived
      model, at significantly less computational cost.

PMID- 16603206
TI  - Application of a color-shift model with heterogeneous growth to a rat
      hepatocarcinogenesis experiment.
AB  - Several hypotheses are established to describe the formation and progression of
      foci of altered hepatocytes (FAH). A common model of hepatocarcinogenesis is the
      mutation model (MM), which is based on the assumption that cells have to undergo
      multiple successive changes on their way from the normal to the malignant stage.
      This model describes growth and phenotype change of foci on the cellular level
      and is based on the assumption that single cells change their phenotype through
      mutation into the next stage and proliferate according to a linear stochastic
      birth-death process. In contrast, the color-shift model (CSM) was introduced by
      Kopp-Schneider et al. to describe that whole colonies of altered hepatocytes
      simultaneously alter their phenotype. In this paper two modifications of the
      color-shift model are considered which allow the growth rate to vary from focus
      to focus. All four models are compared with respect to their ability to predict
      number and radii of foci in a rat hepatocarcinogenesis experiment, in which rats
      were treated with the carcinogens N-nitrosomorpholine, 2-acetylaminofluoren and
      Phenobarbital. Maximum likelihood parameter estimates are given, and predicted
      and empirical FAH size distributions are visualized. The Cramer-von-Mises
      distance is used as a measure for the discrepancy between empirical and
      theoretical size distributions.

PMID- 16603207
TI  - Simulations of rubella vaccination strategies in China.
AB  - Many infants whose mothers have rubella infections during their first trimester
      of pregnancy have birth defects called congenital rubella syndrome (CRS). China
      does not routinely vaccinate against rubella in the public sector, but may need
      to start as its 'one child per couple' policy changes the population age
      distribution and the dynamics of rubella epidemiology, so that the incidence of
      rubella in pregnant women increases. Computer simulations with demographic
      transitions and rubella transmission dynamics predict that, with no or limited
      rubella vaccination, CRS incidence in China in the 30 years after 2020 will be
      more than twice the level in 2005. Comparisons of rubella vaccination strategies
      using computer simulations show that routine vaccination of over 80% of 1-year
      old children would be effective in reducing total CRS cases in 2005-2051 and
      eliminating rubella in China by 2051. Routine immunizations at higher levels and
      the addition of early mass vaccinations of 2-14-year-old children and women of
      childbearing ages would further reduce total CRS cases and speed up the
      elimination of rubella.

PMID- 16603208
TI  - A longitudinal evaluation of urinary cortisol in kennelled dogs, Canis
      familiaris.
AB  - Urinary cortisol levels (based on cortisol : creatinine ratios) were evaluated in
      a randomly selected sample of shelter dogs kennelled over a 31-day period. Urine
      was collected on days 2, 5, 10, 17, 24 and 31 (with day 1 referring to the day of
      admittance to the shelter). Cortisol levels peaked on day 17 and steadily
      declined thereafter, although a high degree of individual variation was found,
      with cortisol levels peaking sooner in some dogs. Cortisol levels in kennelled
      dogs were significantly higher on all days except d 31 than the baseline measures
      taken from 20 dogs in their home environments. There were no differences between
      cortisol levels in male and female dogs on each day of sampling and there was no
      significant linear correlation between age and cortisol levels. The results are
      discussed in relation to stress management and the welfare of kennelled dogs.

PMID- 16603210
TI  - Serotonergic characteristics of rainbow trout divergent in stress responsiveness.
AB  - Juvenile rainbow trout divergent in their cortisol response to confinement stress
      (HR: high responsive or LR: low responsive fish) were exposed to either 1 or 3 h
      of confinement stress. Untreated fish served as control. After the exposure blood
      and brain samples were collected. From the blood samples, the levels of cortisol
      and catecholamines were determined, while the brain serotonergic and
      monoamineoxidase (MAO) activity was determined in four different brain areas
      (brain stem, hypothalamus, telencephalon and optic tectum). Our results show that
      the LR fish responds to handling stress with a higher increase in plasma
      epinephrine compared to HR fish. Our results also show that confinement stress
      leads to a larger increase in the serotonergic activity in the brain stem and
      telencephalon in LR fish compared to HR fish. These results support the
      hypothesis that stress coping strategies similar to those described in mammals
      also exists in fish. Further, our results have shown that the MAO activity
      increases in optic tectum and hypothalamus of rainbow trout during confinement
      stress, while it remains unchanged or decreases in brain stem and telencephalon.
      Moreover, the MAO activity does not differ between the two selection lines. This
      indicates that MAO participates actively in the stress response without
      contributing to the differences in stress coping strategies.

PMID- 16603209
TI  - Iron deficiency affects acoustic startle response and latency, but not prepulse
      inhibition in young adult rats.
AB  - Iron deficiency is associated with alterations in dopamine and serotonin
      transporters as well as changes in dopamine receptor (DR) density, monoamine
      concentrations, and in vivo extracellular contents of monoamines in terminal
      fields. Human infants with iron deficiency have both delayed maturation as well
      as lengthened central conduction times in auditory evoked potential studies. The
      current study utilizes the magnitude of the acoustic startle response (ASR),
      prepulse inhibition (PPI), and mean latency to maximum startle response (T(max)),
      to examine the functional integrity of response to environmental cues. Male and
      female rats consumed iron deficient (ID) or iron adequate (CN) diets from weaning
      until adulthood. ID rats of both sexes had 20-60% reductions in ASR when compared
      to CN rats but there was no effect on PPI. T(max) was significantly longer by 10
      20% in females, but not males. Dopamine transporter density was significantly
      lower in putamen, nucleus accumbens, and olfactory tubercle in males, but not
      female rats while the serotonin transporter was significantly different from
      control animal density in five of 14 brain regions. Norepinephrine transporter
      density was lower in the locus ceruleus of ID male rats but was unaffected in ID
      female rats. Regression modeling of ASR with brain monoamine transporters and
      receptors showed hematocrit, norepinephrine transporter (NET) in dentate gyrus,
      and D1R in the nucleus accumbens account for nearly 49% of the variance in ASR.
      T(max) was not significantly associated with any of the independent variables. We
      conclude that iron deficiency affects the startle response, but not the
      inhibitory circuits involved in prepulse inhibition. Importantly, sex also
      strongly influenced these behavioral responses. Future studies, perhaps
      pharmacologic in nature, are necessary to ascertain whether iron deficiency
      modifies the contribution of monoaminergic systems to responses to environmental
      stimuli.

PMID- 16603211
TI  - Purification and characterization of a serine protease from Cucumis trigonus
      Roxburghi.
AB  - Kachri fruit, Cucumis trigonus Roxburghi, contains high protease activity and has
      been used as meat tenderizer in the Indian subcontinent. A 67 kDa serine protease
      from Kachri fruit was purified by DEAE-Sepharose and CM-Sepharose chromatography,
      whose optimum activity was at pH 11 and 70 degrees C. Its activity was strongly
      inhibited by PMSF, but not by EDTA, pepstatin, or cysteine protease inhibitors.
      The substrate specificity of the purified protease towards synthetic peptides was
      comparable to cucumisin, the first characterized subtilisin class plant protease
      from the sarcocarp of melon fruit (Cucumis melo). These characteristics, along
      with the N-terminal amino acid sequence, indicated that the isolated protease
      from Cucumis trigonus Roxburghi is a cucumisin homologue, which belongs to the
      serine protease family.

PMID- 16603212
TI  - Bioreduction of aldehydes and ketones using Manihot species.
AB  - Biocatalysis constitutes an important tool in organic synthesis, especially for
      the preparation of chiral molecules of biological interest. A series of aliphatic
      and aromatic aldehydes and two ketones were reduced using plant cell preparations
      from Manihot esculenta and Manihot dulcis roots. The reduced products were
      typically obtained in excellent yields (80-96%), and with excellent enantiomeric
      excess (94-98%), except for vanillin. Esters, a nitrile, and an amide were also
      examined, but were not reduced. Preliminary conversion rate studies are reported.
      This is the first attempt to perform the biotransformation of carbonyl compounds
      using Manihot species.

PMID- 16603213
TI  - Up-regulation of cytosolic phospholipase A2alpha expression by N,N
      diethyldithiocarbamate in PC12 cells; involvement of reactive oxygen species and
      nitric oxide.
AB  - Disulfiram (an alcohol-aversive drug) and related compounds are known to provoke
      several side effects involving behavioral and neurological complications. N,N
      diethyldithiocarbamate (DDC) is considered as one of the main toxic species of
      disulfiram and acts as an inhibitor of superoxide dismutase. Since arachidonic
      acid (AA) formation is regulated by reactive oxygen species (ROS) and related to
      toxicity in neuronal cells, we investigated the effects of DDC on AA release and
      expression of the alpha type of cytosolic phospholipase A(2) (cPLA(2)alpha) in
      PC12 cells. Treatment with 80-120 microM DDC that causes a moderate increase in
      ROS levels without cell toxicity stimulated cPLA(2)alpha mRNA and its protein
      expression. The expression was mediated by extracellular-signal-regulated kinase
      (ERK1/2), one of the mitogen-activated protein kinases. Treatment with N(G) nitro
      L-arginine methyl ester (an inhibitor of nitric oxide synthase, 1 mM) and oxy
      hemoglobin (a scavenger of nitric oxide, 2 mg/mL) abolished the DDC-induced
      responses (ERK1/2 phosphorylation and cPLA(2)alpha expression). We also showed
      DDC-induced up-regulation of the mRNA expression of lipocortin 1, an inhibitor of
      PLA(2). Furthermore, DDC treatment of the cells enhanced Ca(2+)-ionophore-induced
      AA release in 30 min, although the effect was limited. Changes in AA metabolism
      in DDC-treated cells may have a potential role in mediating neurotoxic actions of
      disulfiram. In this study, we show the first to demonstrate the up-regulation of
      cPLA(2)alpha expression by DDC treatment in neuronal cells.

PMID- 16603215
TI  - The cysteine-histidine-rich region of the movement protein of Cucumber mosaic
      virus contributes to plasmodesmal targeting, zinc binding and pathogenesis.
AB  - Viral movement proteins (MPs) are central to the establishment of viral
      pathogenesis, and yet relatively little is understood about the structural and
      functional aspects of MPs or about the host factors on which they depend. Through
      chemical mutagenesis of transgenic Arabidopsis expressing Cucumber mosaic virus
      (CMV) MP fused with the green fluorescent protein, we have studied the function
      of a central region of the MP, defined by a number of conserved cysteine and
      histidine residues (Cys-His-rich region), which potentially functions as a zinc
      binding domain. Transient expression of mutant MPs identified through an in
      planta screen for altered MP function or constructed with altered putative zinc
      ligands through site-directed mutagenesis showed that mutations in the Cys-His
      rich region affected localization to and trafficking through plasmodesmata. In
      vitro zinc-binding analysis revealed that wild type (wt) CMV MP had the ability
      to bind zinc and that movement-defective mutants bound zinc with less affinity
      than wt MP. Furthermore, a correlation between the association of the MP with
      plasmodesmata and virus pathogenesis was shown. We discuss roles of the Cys-His
      region in biochemical and biological functions of the MP during virus movement.

PMID- 16603214
TI  - Bioactivation, protein haptenation, and toxicity of sulfamethoxazole and dapsone
      in normal human dermal fibroblasts.
AB  - Cutaneous drug reactions (CDRs) associated with sulfonamides are believed to be
      mediated through the formation of reactive metabolites that result in cellular
      toxicity and protein haptenation. We evaluated the bioactivation and toxicity of
      sulfamethoxazole (SMX) and dapsone (DDS) in normal human dermal fibroblasts
      (NHDF). Incubation of cells with DDS or its metabolite (D-NOH) resulted in
      protein haptenation readily detected by confocal microscopy and ELISA. While the
      metabolite of SMX (S-NOH) haptenated intracellular proteins, adducts were not
      evident in incubations with SMX. Cells expressed abundant N-acetyltransferase-1
      (NAT1) mRNA and activity, but little NAT2 mRNA or activity. Neither NAT1 nor NAT2
      protein was detected. Incubation of NHDF with S-NOH or D-NOH increased reactive
      oxygen species formation and reduced glutathione content. NHDF were less
      susceptible to the cytotoxic effect of S-NOH and D-NOH than are keratinocytes.
      Our studies provide the novel observation that NHDF are able to acetylate both
      arylamine compounds and bioactivate the sulfone DDS, giving rise to haptenated
      proteins. The reactive metabolites of SMX and DDS also provoke oxidative stress
      in these cells in a time- and concentration-dependent fashion. Further work is
      needed to determine the role of the observed toxicity in mediating CDRs observed
      with these agents.

PMID- 16603217
TI  - Novel antiviral activity of chemokines.
AB  - Antimicrobial peptides are a diverse family of small, mostly cationic
      polypeptides that kill bacteria, fungi and even some enveloped viruses, while
      chemokines are a group of mostly cationic small proteins that induce directed
      migration of leukocytes through interactions with a group of seven transmembrane
      G protein-coupled receptors. Recent studies have shown that antimicrobial
      peptides and chemokines have substantially overlapping functions. Thus, while
      some antimicrobial peptides are chemotactic for leukocytes, some chemokines can
      kill a wide range of bacteria and fungi. Here, we examined a possible direct
      antiviral activity of chemokines against an enveloped virus HSV-1. Among 22 human
      chemokines examined, chemokines such as MIP-1 alpha/CCL3, MIP-1 beta/CCL4 and
      RANTES/CCL5 showed a significant direct antiviral activity against HSV-1. It is
      intriguing that these chemokines are mostly known to be highly expressed by
      effector CD8+ T cells. The chemokines with a significant anti-HSV-1 activity
      commonly bound to HSV-1 virions via envelope glycoprotein gB. Electron microscopy
      revealed that the chemokines with a significant anti-HSV-1 activity were commonly
      capable of generating pores in the envelope of HSV-1. Thus, some chemokines have
      a significant direct antiviral activity against HSV-1 in vitro and may have a
      potential role in host defense against HSV-1 as a direct antiviral agent.

PMID- 16603216
TI  - Characterization of polymorphism displayed by the coat protein mutants of tomato
      bushy stunt virus.
AB  - Expression of full-length and N-terminal deletion mutants of the coat protein
      (CP) of tomato bushy stunt virus (TBSV) using the recombinant baculovirus system
      resulted in spontaneously assembled virus-like particles (VLPs). Deletion of the
      majority of the R-domain sequence of the CP, residues 1-52 (CP-NDelta52) and 1-62
      (CP-NDelta62), produced capsids similar to wild-type VLPs. Interestingly, the CP
      NDelta62 mutant that retains the last 3 residues of R-domain is capable of
      forming both the T = 1 and T = 3 particles. However, between the two types of
      VLPs, formation of the T = 1 capsids appears to be preferred. Another mutant, CP
      NDelta72, in which R-domain (residues 1-65) was completely removed but contains
      most of the beta-annulus and extended arm (betaA) regions exclusively formed T =
      1 particles. These results suggest that as few as 3 residues (63-65) of the R
      domain, which includes 2 basic amino acids together with the arm (betaA) and beta
      annulus regions, may be sufficient for the formation of T = 3 particles. However,
      anywhere between 4 to 13 residues of the R-domain may be required for proper
      positioning of betaA and beta-annulus structural elements of the C-type subunits
      to facilitate an error free assembly of T = 3 capsids.

PMID- 16603218
TI  - Gradient representation and perception in the early visual system--a novel
      account of Mach band formation.
AB  - Recent evidence suggests that object surfaces and their properties are
      represented at early stages in the visual system of primates. Most likely
      invariant surface properties are extracted to endow primates with robust object
      recognition capabilities. In real-world scenes, luminance gradients are often
      superimposed on surfaces. We argue that gradients should also be represented in
      the visual system, since they encode highly variable information, such as
      shading, focal blur, and penumbral blur. We present a neuronal architecture which
      was designed and optimized for segregating and representing luminance gradients
      in real-world images. Our architecture in addition provides a novel theory for
      Mach bands, whereby corresponding psychophysical data are predicted consistently.

PMID- 16603219
TI  - Dynamic and static adsorption and desorption of Hg(II) ions on chitosan membranes
      and spheres.
AB  - The adsorption and desorption of Hg(II) ions was studied using static and dynamic
      methods, employing membranes and spheres of chitosan as the adsorbent. The
      quantity of adsorption was influenced by chitosan crosslinking and by the
      adsorbent shape. The Langmuir model was applied to fit the experimental
      equilibrium data. Glutaraldehyde-crosslinked membranes presented a lower
      desorption capacity, when compared to natural membranes, but could be regenerated
      for use in successive cycles. Dynamic adsorption experiments suggested that the
      adsorption capacity depended mainly on adsorbent geometry, due to differences
      between surface area to mass ratio and initial concentration of Hg(II) ions. The
      adsorption capacity determined by the dynamic method was 65% and 77% for
      membranes and spheres, respectively of the value obtained static method results.
      A process combining dynamic adsorption and static desorption can be used to
      concentrate the Hg(II) ions by a factor of nearly seven (7x), when compared to
      the initially treated volume.

PMID- 16603220
TI  - Kinetic and metabolic study of benzene, toluene and m-xylene in nitrifying batch
      cultures.
AB  - The effect of benzene, toluene, and m-xylene (BTX) compounds on the nitrifying
      activity of a sludge produced in steady-state nitrification was evaluated in
      batch cultures. Benzene and m-xylene at 10 mg C/L decreased ammonium consumption
      efficiency by 57% and 26%, respectively, whereas toluene did not affect the
      ammonium oxidation process. The consumed NH4+-N was totally oxidized to NO3- -N.
      There was no significant effect at 5 mg C/L of each aromatic compound. BTX (5
      20mg C/L) induced a significant decrease in the values for specific rates of NH4+
      -N consumption (76-99%) and NO3- -N production (45-98%). At 10 mg C/L of BTX
      compounds, the inhibition order on nitrate production was: benzene > m-xylene >
      toluene while at 20 mg C/L, the sequence changed to m-xylene > toluene > benzene
      for both nitrification inhibition and BTX compounds persistence. At 5 mg C/L of
      BTX compounds, there was no toxic effect on the sludge whereas from 10 to 50
      mgC/L, bacteria did not totally recover their nitrifying activity. At a
      concentration of 5 mg C/L, toluene was first oxidized to benzyl alcohol, which
      was later oxidized to butyrate while m-xylene was oxidized to acetate and
      butyrate.

PMID- 16603221
TI  - A quantitative measure of nitrifying bacterial growth.
AB  - Nitrifying bacteria convert ammonia (NH3) to nitrate (NO3-) in a nitrification
      reaction. Methods to quantitatively separate the growth rate of these important
      bacterial populations from that of the dominant heterotrophic bacteria are
      important to our understanding of the nitrification process. The changing
      concentration of ammonia is often used as an indirect measure of nitrification
      but ammonification processes generate ammonia and confound this approach while
      heterotrophs remove nitrate via denitrification. Molecular probe methods can tell
      us what proportion of the microbial community is nitrifying bacteria but not
      their growth rate. The technique proposed here was able to quantify the growth
      rate of the nitrifying bacterial populations amidst complex ecological processes.
      The method incubates [methyl-3H] thymidine with water samples in the presence and
      absence of an inhibitor of nitrification-thiourea. The radioactively labeled DNA
      in the growing bacteria was extracted. The rate of incorporation of the label
      into the dividing bacterial DNA was used to determine bacterial growth rate.
      Total bacterial community growth rates in full-scale and pilot-scale fixed-film
      nitrifying reactors and an activated sludge reactor were 2.1 x 10(8), 4.1 x 10(8)
      and 0.4 x 10(8)cell ml(-1)d(-1), respectively; the growth rate of autotrophic
      nitrifying bacteria was 0.7 x 10(8), 2.6 x 10(8) and 0.01 x 10(8)cell ml(-1)d(
      1), respectively. Autotrophic-nitrifying bacteria contributed 30% and 60% of the
      total bacterial community growth rate in the nitrifying reactors whereas only 2%
      was observed in the activated sludge reactor that was not designed to nitrify.
      The rates of ammonia loss from the nitrifying reactors corresponded to the rate
      of growth of the nitrifying bacteria. This method has the potential to more often
      identify factors that enhance or limit nitrifying processes in both engineered
      and natural aquatic environments.

PMID- 16603222
TI  - Antimicrobial resistance in Enterococcus spp. isolated in inflow, effluent and
      sludge from municipal sewage water treatment plants.
AB  - Antimicrobial resistance of enterococci was investigated in 42 samples of crude
      inflow, treated effluent and sludge collected in 14 municipal sewage treatment
      plants of Portugal. A total of 983 enterococci were recovered and tested, using
      the diffusion agar method, regarding their sensitivity to 10 different
      antimicrobial drugs. Multidrug resistance was present in 49.4% of the isolates.
      Only 3.3% and 0.6% of the investigated strains were resistant to ampicillin and
      vancomycin, respectively. Resistances found against rifampicin (51.5%),
      tetracycline (34.6%), erythromycin (24.8%) and nitrofurantoin (22.5%), are causes
      for substantial concern. Almost 14% of isolates were resistant to ciprofloxacin.
      Wastewater treatment resulted in enterococci decrease between 0.5 and 4log;
      nevertheless, more than 4.4 x 10(5)CFU/100ml were present in the outflow of the
      plants. Our data indicate that the use of antimicrobials had created a large pool
      of resistance genes and that sewage treatment processes are unable to avoid the
      dissemination of resistant enterococci into the environment.

PMID- 16603223
TI  - The importance of atmospheric deposition, charge and atomic mass to the dynamics
      of minor and rare elements in developing, ageing, and wilted leaves of beech
      (Fagus sylvatica L.).
AB  - The amounts of sixty elements in developing, maturing, senescent and wilting
      leaves, and in the wintering dead leaves attached to the branches, are reported
      for a beech (Fagus sylvatica) forest on mor Podzol in south Sweden, a site with
      no local sources of pollution or geological anomalies. The amounts (contents per
      leaf) of K (potassium), Rb (rubidium), Cs (caesium), Cu (copper) and P
      (phosphorus) were highest in young leaves, decreasing throughout the growing
      season and usually in the subsequent winter. The entirely opposite pattern with a
      continuous, mostly even increase of the amounts was measured with Be (beryllium),
      Ba (barium), Hg (mercury), Al (aluminium), Tl (thallium), Pb (lead), Bi
      (bismuth), V (vanadium), W (tungsten), As (arsenic), Sb (antimony), and Se
      (selenium). Amounts of rare-earth elements and some transition metals, such as Co
      (cobalt), Ti (titanium), and the actinides Th (thorium) and U (uranium) were more
      stable during the growing season, after an initial increase in early summer, but
      increased greatly in the winter. This winter increase in dead attached leaves has
      to be accounted for by uptake from long-distance transported constituents in dry
      and wet deposition. It was similar to deposition rate estimates using moss
      carpets from the same locality. A passive uptake was positively related to ionic
      charge and atomic mass. However, the amounts of several, mainly non-essential
      elements, such as Ni (nickel), Sc (scandium), Zr (zirconium), Cr (chromium), Ag
      (silver), and Cd (cadmium) were not much lower in the young or maturing leaves
      than in the wintered dead leaves of this deciduous (hardwood) forest and a
      proportion apparently originated from internal translocation in the trees.
      Seasonal fluxes or cycling of many of the scarce or rare elements reported here
      have never been studied before in forest ecosystems.

PMID- 16603224
TI  - Influence of the colloid type on the transfer of 60Co and 85Sr in silica sand
      column under varying physicochemical conditions.
AB  - The influence of two types of colloids (natural organic matter, NOM), a colloid
      with high affinity for radionuclides (RN(s)), and hydrophilic synthetic latex
      (SHL), a colloid with low affinity for RN(s) on the transfer of (60)Co and (85)Sr
      in a silica sand column was studied under different physicochemical conditions:
      pH (4.9), ionic strength (10(-3) M and 10(-2) M), concentration of colloids (100
      mg l(-1), 10 mg l(-1)), flow velocity (12.4 cm h(-1) and 3.7 cm h(-1)), water
      saturation of the column (100% and 70%). In the absence of colloids, the transfer
      of (60)Co and (85)Sr was retarded compared to the transfer of the conservative
      tracer. In the presence of colloids and according to the specific physicochemical
      conditions, an acceleration or retardation of (60)Co and (85)Sr transfer was
      observed compared to their transfer in the absence of colloids. Our results
      evidenced that any colloids even with low reactivity could significantly modify
      the RN transfer. However, the extent to which the transfer was influenced differs
      according to the colloid type; the NOM exhibiting higher impact than SHL. Batch
      experiments helped in interpreting of the interactions between the colloids,
      RN(s) and solid phase observed in column.

PMID- 16603225
TI  - Quantification of total native compounds on phenanthrene-specific adsorption
      sites in the very slow desorption domain of 16 sediments and soils.
AB  - We determined the maximum amount of added phenanthrene that could be adsorbed in
      the very slow desorption domain of 16 sediments and soils with and without native
      compounds present. The differences in the amount of phenanthrene taken up in this
      domain with and without native compounds present indicates to what extent native
      compounds occupy those adsorption sites in the very slow desorption domain which
      may accommodate phenanthrene. For the two aquifer materials, presence of native
      compounds was less than the uncertainty associated with the methodology. For the
      sediments, 41-84% of the adsorption sites appeared to be occupied by native
      compounds.

PMID- 16603226
TI  - Alleviation of Cd toxicity by composted sewage sludge in Cd-treated Schmidt birch
      (Betula schmidtii) seedlings.
AB  - We investigated alleviation of Cd toxicity and changes in the physiological
      characteristics of Betula schmidtii seedlings following application of composted
      sewage sludge to Cd-treated plants. Plants were grown under four test conditions:
      control, Cd treatment, sludge amendment, and Cd treatment with sludge amendment.
      B. schmidtii treated with Cd only accumulated the greatest amount of Cd in the
      leaves, but absorbed Cd was also highly concentrated in the roots. In contrast,
      Cd concentrations in the Cd and sludge amendment treated seedlings were the
      lowest in the roots. Since sludge amendment increased the growth of seedlings, it
      may have alleviated toxicity by dilution of Cd. Additionally, the absorbed Cd was
      more widely distributed since it was transported from the roots and accumulated
      in the stems and leaves of Cd and sludge treated plants. Cd treatment inhibited
      the growth and physiological functions of B. schmidtii seedlings, but sludge
      amendment compensated for these effects and improved growth and physiological
      functions in both Cd-treated and control plants. SOD activity in the leaves of
      seedlings was increased in the Cd-treated plants, but not in the Cd and sludge
      amendment treated seedlings. In conclusion, alleviation of Cd toxicity in
      response to sludge amendment may be related to a dilution effect, in which the Cd
      concentration in the tissues was effectively lowered by the improved growth
      performance of the seedlings.

PMID- 16603227
TI  - Arbuscular mycorrhizae increase the arsenic translocation factor in the As
      hyperaccumulating fern Pteris vittata L.
AB  - Phytoremediation techniques are receiving more attention as decontaminating
      strategies. Phytoextraction makes use of plants to transfer contaminants from
      soil to the aboveground biomass. This research is devoted to study the effects of
      arbuscular mycorrhizae (AM) on growth and As hyperaccumulation in the Chinese
      brake fern Pteris vittata. We grew for 45 days P. vittata sporophytes, infected
      or not infected with the AM fungi Glomus mosseae or Gigaspora margarita, in a
      hydroponic system on quartz sand. As-treated plants were weekly fed with 25 ppm
      As. The As treatment produced a dramatic increase of As concentration in pinnae
      and a much lower increase in roots of both mycorrhizal and control plants.
      Mycorrhization increased pinnae dry weight (DW) (G. margarita = G. mosseae) and
      leaf area (G. margarita > G. mosseae), strongly reduced root As concentration (G.
      mosseae > G. margarita), and increased the As translocation factor (G. mosseae >
      G. margarita). The concentration of phosphorus in pinnae and roots was enhanced
      by both fungi (G. margarita > G. mosseae). The quantitatively different effects
      of the two AM fungi on plant growth as well as on As and P distribution in the
      fern suggest that the As hyperaccumulation in P. vittata can be optimized by a
      careful choice of the symbiont.

PMID- 16603228
TI  - SIRT1 stimulation by polyphenols is affected by their stability and metabolism.
AB  - Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the
      yeast sir2 protein; one of the most important regulators of lifespan extension by
      caloric restriction in several organisms. Dietary polyphenols, abundant in
      vegetables, fruits, cereals, wine and tea, were reported to stimulate the
      deacetylase activity of recombinant SIRT1 protein and could therefore be
      potential regulators of aging associated processes. However, inconsistent data
      between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led
      us to investigate the influence of (1) stability of polyphenols under
      experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on
      stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three
      new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold),
      epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1
      under stabilizing conditions, whereas without stabilization, these polyphenols
      strongly inhibited SIRT1, probably due to H2O2 formation. Using metabolically
      active HT29 cells we were able to show that quercetin (a stimulator of
      recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin
      metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the
      recombinant SIRT1 activity which explains the lack of stimulatory action of
      quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is
      strongly affected by polyphenol stability and metabolism, therefore extrapolation
      of in vitro SIRT1 stimulation results to physiological effects should be done
      with caution.

PMID- 16603229
TI  - Field drains as a route of rapid nutrient export from agricultural land receiving
      biosolids.
AB  - We report research on the environmental risk of incidental nutrient transfers
      from land to water for biosolids amended soils. We show that subsurface
      (drainflow) pathways of P transport may result in significant concentrations, up
      to 10 mg total P l(-1), in the drainage network of an arable catchment when a P
      source (recent biosolids application) coincides with a significant and active
      transport pathway (rainfall event). However, the high P concentrations were short
      lived, with drainage ditch total P concentrations returning to pre-storm
      concentrations within a few days of the storm event. In the case of the drainflow
      concentrations reported here, the results are unusual in that they describe an
      'incidental event' for a groundwater catchment where such events might normally
      be expected to be rare owing to the capacity of the hydrological system to
      attenuate nutrient fluxes for highly adsorbed elements such as P. Consequently,
      there is a potential risk of P transfers to shallow groundwater systems. We
      suggest that the findings are not specific to biosolids-alone, which is a highly
      regulated industry, but that similar results may be anticipated had livestock
      waste or mineral fertilizer been applied, although the magnitude of losses may
      differ. The risk appears to be more one of timing and the availability of a rapid
      transport pathway than of P source.

PMID- 16603230
TI  - Impacts of climate change on in-stream nitrogen in a lowland chalk stream: an
      appraisal of adaptation strategies.
AB  - The impacts of climate change on nitrogen (N) in a lowland chalk stream are
      investigated using a dynamic modelling approach. The INCA-N model is used to
      simulate transient daily hydrology and water quality in the River Kennet using
      temperature and precipitation scenarios downscaled from the General Circulation
      Model (GCM) output for the period 1961-2100. The three GCMs (CGCM2, CSIRO and
      HadCM3) yield very different river flow regimes with the latter projecting
      significant periods of drought in the second half of the 21st century. Stream
      water N concentrations increase over time as higher temperatures enhance N
      release from the soil, and lower river flows reduce the dilution capacity of the
      river. Particular problems are shown to occur following severe droughts when N
      mineralization is high and the subsequent breaking of the drought releases high
      nitrate loads into the river system. Possible strategies for reducing climate
      driven N loads are explored using INCA-N. The measures include land use change or
      fertiliser reduction, reduction in atmospheric nitrate and ammonium deposition,
      and the introduction of water meadows or connected wetlands adjacent to the
      river. The most effective strategy is to change land use or reduce fertiliser
      use, followed by water meadow creation, and atmospheric pollution controls.
      Finally, a combined approach involving all three strategies is investigated and
      shown to reduce in-stream nitrate concentrations to those pre-1950s even under
      climate change.

PMID- 16603231
TI  - Whole blood aggregometry for evaluation of the antiplatelet effects of
      clopidogrel.
AB  - INTRODUCTION: The marked interindividual variability in platelet inhibition even
      after administration of high loading doses of clopidogrel raised the question
      whether monitoring of antiplatelet effects in patients undergoing percutaneous
      coronary intervention (PCI) can improve clinical outcome. Established methods for
      monitoring antiplatelet drug activity such as optical aggregometry and
      determination of surface protein expression are not suitable for routine bedside
      testing. MATERIAL AND METHODS: We therefore compared the applicability of whole
      blood impedance aggregometry (20 micromol/L ADP) and the whole blood bedside
      ULTEGRA assay with ADP-cartridges (20 micromol/L) with optical aggregometry in
      platelet-rich plasma and determination of surface protein expression (P-Selectin
      and activated GPIIb/IIIa) by flow cytometry. We analyzed samples obtained from 27
      patients scheduled for elective PCI who received a loading dose of 600 mg of
      clopidogrel. Blood samples were withdrawn before clopidogrel, before PCI and 24h
      thereafter. RESULTS: Platelet aggregation assessed by optical aggregometry (20
      micromol/L ADP) declined from 65+/-9% (baseline) to 42+/-12% (PCI) and 45+/-13%
      (24h; p<0.01). Expression of surface proteins displayed a similar time course.
      Platelet aggregation determined by impedance aggregometry decreased from 4.6+/
      4.0 Omega (baseline) to 0.1+/-0.3 Omega (PCI) and 0.5+/-1.1 Omega (24h) with no
      detectable residual platelet aggregation during PCI in 88% of patients. The
      ULTEGRA assay showed only slight changes after administration of clopidogrel.
      Correlation analysis between the various assays revealed significant correlations
      only between optical aggregometry and flow cytometry. CONCLUSIONS: The results
      indicate that both of the whole blood assays cannot substitute for optical
      aggregometry or determination of surface proteins in the assessment of
      clopidogrel-induced platelet inhibition.

PMID- 16603232
TI  - The challenge resulting from positive and negative effects of sunlight: how much
      solar UV exposure is appropriate to balance between risks of vitamin D deficiency
      and skin cancer?
AB  - There is no doubt that solar ultraviolet (UV) exposure is the most important
      environmental risk factor for the development of non-melanoma skin cancer.
      Therefore, sun protection is of particular importance to prevent these
      malignancies, especially in risk groups. However, 90% of all requisite vitamin D
      has to be formed in the skin through the action of the sun-a serious problem, for
      a connection between vitamin D deficiency and a broad variety of independent
      diseases including various types of cancer, bone diseases, autoimmune diseases,
      hypertension and cardiovascular disease has now been clearly indicated in a large
      number of epidemiologic and laboratory studies. An important link that improved
      our understanding of these new findings was the discovery that the biologically
      active vitamin D metabolite 1,25(OH)(2)D is not exclusively produced in the
      kidney, but in many other tissues such as prostate, colon, skin and osteoblasts.
      Extra-renally produced 1,25(OH)(2)D is now considered to be an autocrine or
      paracrine hormone, regulating various cellular functions including cell growth.
      We and others have shown that strict sun protection causes vitamin D deficiency
      in risk groups. In the light of new scientific findings that convincingly
      demonstrate an association of vitamin D deficiency with a variety of severe
      diseases including various cancers, the detection and treatment of vitamin D
      deficiency in sun-deprived risk groups is of high importance. It has to be
      emphasized that in groups that are at high risk of developing vitamin D
      deficiency (e.g., nursing home residents or patients under immunosuppressive
      therapy), vitamin D status has to be monitored. Vitamin D deficiency should be
      treated, e.g., by giving vitamin D orally. Dermatologists and other clinicians
      have to recognize that there is convincing evidence that the protective effect of
      less intense solar UV radiation outweighs its mutagenic effects. Although further
      work is necessary to define an adequate vitamin D status and adequate guidelines
      for solar UV exposure, it is at present mandatory that public health campaigns
      and recommendations of dermatologists on sun protection consider these facts.
      Well-balanced recommendations on sun protection have to ensure an adequate
      vitamin D status, thereby protecting people against adverse effects of strict sun
      protection without significantly increasing the risk of developing UV-induced
      skin cancer.

PMID- 16603233
TI  - Development of the ventromedial nucleus of the hypothalamus.
AB  - The ventromedial nucleus of the hypothalamus (VMH) is important in the regulation
      of female sexual behavior, feeding, energy balance, and cardiovascular function.
      It is a highly conserved nucleus across species and a good model for studying
      neuronal organization into nuclei. Expression of various transcription factors,
      receptors, and neurotransmitters are important for the development of this
      nucleus and for mapping the position of identified cells within the nucleus. The
      VMH is subdivided into regions, all of which may project to specific locations to
      carry out various functions. For example, the ventrolateral quadrant contains a
      subset of neurons that highly express estrogen receptors. These neurons
      specifically are involved in the lordosis response pathway through projections to
      other estrogen receptor containing regions. In development, neurons that form the
      VMH generate from the proliferative zone surrounding the third ventricle. Neurons
      then migrate along radial glial fibers to final positions within the nucleus.
      Migration and positioning of neurons is an important step in setting up
      connections to and from the VMH and hence in its function. As compared to other
      developing brain regions, cell death may play a minor role in sculpting the VMH.
      We review the processes involved in forming a functional nuclear group and some
      of the factors known to be involved particularly focusing on the positioning of
      identified neurons within the VMH.

PMID- 16603234
TI  - New roles for estrogen receptor beta in behavior and neuroendocrinology.
AB  - In this review we critically examine the data on functions of the estrogen
      receptor beta (ERbeta) in both behavior and neuroendocrinology. The influence of
      estradiol via the ERbeta has been assessed using several methods: estrogen
      receptor knockout mice, specific ERbeta selective agonists, and phytoestrogens
      which preferentially bind to ERbeta rather than ERalpha. The behavior for which a
      solid database and consensus is forming is anxiety; activation of ERbeta reduces
      anxiety on a number of tasks and in several species. Moreover, the relationship
      between ERbeta and serotonin may be critical for the regulation of this behavior
      by estradiol. There have been very few studies on learning and memory but the
      little we know suggests that ERbeta is involved in visuospatial learning; in its
      absence learning is inhibited. Recent work has suggested a unique function for
      ERbeta in sexual differentiation; its activation in male neonates may promote
      defeminization of sexual behavior. Several neurotransmitter-containing neurons in
      the rat paraventricular nucleus coexpress ERbeta including; vasopressin,
      oxytocin, prolactin, and to a lesser extent corticotrophin releasing hormone.
      Given the potential for ERbeta to interact with these important neurotransmitters
      and its co-expression in gonadotropin releasing hormone neurons it is surprising
      how normal the hypothalamic-pituitary-adrenal and -gonadal axes appear to be in
      ERbeta knockout mice. Either this represents a species difference (the
      neuroanatomy has been conducted in the rat) or compensatory actions of ERalpha or
      other mechanisms. Exciting avenues for future research include; in vivo
      interactions between ERalpha and ERbeta, actions of non-estrogenic ligands with
      ERbeta, and the role of ERbeta in sexual differentiation.

PMID- 16603235
TI  - Hippocampal neuroplasticity induced by early-life stress: functional and
      molecular aspects.
AB  - Whereas genetic factors contribute crucially to brain function, early-life
      events, including stress, exert long-lasting influence on neuronal function.
      Here, we focus on the hippocampus as the target of these early-life events
      because of its crucial role in learning and memory. Using a novel immature-rodent
      model, we describe the deleterious consequences of chronic early-life
      'psychological' stress on hippocampus-dependent cognitive tasks. We review the
      cellular mechanisms involved and discuss the roles of stress-mediating molecules,
      including corticotropin releasing hormone, in the process by which stress impacts
      the structure and function of hippocampal neurons.

PMID- 16603236
TI  - Stacking anabolic androgenic steroids (AAS) during puberty in rats: a
      neuroendocrine and behavioral assessment.
AB  - Anabolic androgenic steroid (AAS) abuse is increasing in teenagers. We examined
      the effects of stacked AAS in adolescent male rats. Stacking, in which multiple
      AAS are taken simultaneously, is commonly employed by humans. Beginning at
      puberty gonadally intact male rats received testosterone, nandrolone, or
      stanozolol. Additional groups received stacked AAS: testosterone + stanozolol,
      nandrolone + stanozolol, or nandrolone + testosterone. Injections continued
      during tests for sexual behavior, vocalizations, scent marking, partner
      preference, aggression and fertility. Body and reproductive tissue weights were
      taken. Sexual and aggressive behaviors were increased by testosterone yet
      inhibited by stanozolol; nandrolone had no effect. Stacking testosterone with
      stanozolol prevented the inhibitory effects of stanozolol. Body weight was
      decreased by testosterone and all stacked AAS. Cell nuclear androgen receptor
      binding in brain was significantly increased in nandrolone males and decreased in
      stanozolol males; testosterone males were slightly higher than controls. Androgen
      receptors in stacked groups were intermediate between individual AAS suggesting
      that stanozolol competed with other AAS for androgen receptors despite its low
      affinity. The results indicate that stacking AAS influences the effects of
      individual AAS on behavioral and endocrine measures, and levels of androgen
      receptor occupation are not directly correlated with AAS effects on behavior.

PMID- 16603237
TI  - JHDM2A, a JmjC-containing H3K9 demethylase, facilitates transcription activation
      by androgen receptor.
AB  - Covalent modification of histones plays an important role in regulating chromatin
      dynamics and transcription. Histone methylation was thought to be an irreversible
      modification until recently. Using a biochemical assay coupled with
      chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which
      specifically demethylates mono- and dimethyl-H3K9. Similar to JHDM1, JHDM2A
      mediated histone demethylation requires cofactors Fe(II) and alpha-ketoglutarate.
      Mutational studies indicate that a JmjC domain and a zinc finger present in
      JHDM2A are required for its enzymatic activity. Overexpression of JHDM2A greatly
      reduced the H3K9 methylation level in vivo. Knockdown of JHDM2A results in an
      increase in the dimethyl-K9 levels at the promoter region of a subset of genes
      concomitant with decrease in their expression. Finally, JHDM2A exhibits hormone
      dependent recruitment to androgen-receptor target genes, resulting in H3K9
      demethylation and transcriptional activation. Thus, our work identifies a histone
      demethylase and links its function to hormone-dependent transcriptional
      activation.

PMID- 16603238
TI  - Reversal of histone lysine trimethylation by the JMJD2 family of histone
      demethylases.
AB  - Histone methylation regulates chromatin structure, transcription, and epigenetic
      state of the cell. Histone methylation is dynamically regulated by histone
      methylases and demethylases such as LSD1 and JHDM1, which mediate demethylation
      of di- and monomethylated histones. It has been unclear whether demethylases
      exist that reverse lysine trimethylation. We show the JmjC domain-containing
      protein JMJD2A reversed trimethylated H3-K9/K36 to di- but not mono- or
      unmethylated products. Overexpression of JMJD2A but not a catalytically inactive
      mutant reduced H3-K9/K36 trimethylation levels in cultured cells. In contrast,
      RNAi depletion of the C. elegans JMJD2A homolog resulted in an increase in
      general H3-K9Me3 and localized H3-K36Me3 levels on meiotic chromosomes and
      triggered p53-dependent germline apoptosis. Additionally, other human JMJD2
      subfamily members also functioned as trimethylation-specific demethylases,
      converting H3-K9Me3 to H3-K9Me2 and H3-K9Me1, respectively. Our finding that this
      family of demethylases generates different methylated states at the same lysine
      residue provides a mechanism for fine-tuning histone methylation.

PMID- 16603239
TI  - DM-nitrophen AM is caged magnesium.
AB  - DM-nitrophen is a photolabile derivative of EDTA and therefore functions as
      either caged Ca(2+) or caged Mg(2+). Several papers have been published recently
      which use the AM ester to load intact cells with DM-nitrophen; under these
      conditions it is caged Mg(2+). In this commentary, I give a short history of the
      development and application of caged Ca(2+) probes, explaining why EGTA and BAPTA
      based Ca(2+) cages are to be preferred for the photorelease of Ca(2+) under
      normal intracellular conditions.

PMID- 16603241
TI  - AML: many new tools for discovery, not enough answers (yet).

PMID- 16603240
TI  - Antineoplastic effect of a single oral dose of the novel Flt3 inhibitor KRN383 on
      xenografted human leukemic cells harboring Flt3-activating mutations.
AB  - Activating mutations of Fms-like tyrosine kinase 3 (Flt3) are the most common
      genetic abnormalities found in acute myeloid leukemia (AML) and represent
      potential therapeutic targets. The novel Flt3 inhibitor KRN383 inhibited the
      autophosphorylation of Flt3 bearing internal tandem duplications (ITDs) and the
      Asp835Tyr (D835Y) point mutation with half-maximal inhibitory concentration
      (IC(50)) values of < or =5.9 and 43 nM, respectively. KRN383 also inhibited the
      proliferation of the ITD-positive cell lines with IC(50) values of < or =2.9 nM.
      A single oral administration of 80 mg/kg of KRN383 eradicated ITD-positive
      xenograft tumors in nude mice and prolonged the survival of SCID mice carrying
      ITD-positive AML cells. The effectiveness of a single oral dose of KRN383
      suggests that it has the potential to be used in a wide variety of clinical
      regimens, including multicycle and combination therapies.

PMID- 16603242
TI  - Childhood emotional abuse and disordered eating among undergraduate females:
      mediating influence of alexithymia and distress.
AB  - OBJECTIVE: Drawing from stress-vulnerability and trauma theory (e.g., Rorty &
      Yager, 1996), this paper presents a model of associations among child emotional
      abuse (CEA), alexithymia, general distress (GD), and disordered eating (DE). This
      study extended previous research on psychological outcomes of child physical and
      sexual abuse to explore those of CEA using measures of specific emotionally
      abusive acts. METHOD: Five hundred and eighty-eight female university students
      completed self-report surveys consisting of measures of CEA, alexithymia,
      depression, anxiety, and DE. Structural equation modeling was used to test this
      conceptual model. RESULTS: Comparison between measurement models suggested that
      bulimic behavior is a separate construct from restrictive eating behaviors and
      body dissatisfaction. In the structural model with the best fit, the association
      between CEA and DE was mediated by alexithymia and GD (i.e., a component of
      depression and anxiety). Specifically, CEA was associated with alexithymia, which
      was further related to GD. Then, restrictive eating behaviors and attitudes
      mediated the relation between GD and bulimic behaviors. By analyzing a second,
      nested model, this latter pathway was shown to be important. CONCLUSION: While
      the best-fitting model is only one of many possibilities, these results point to
      a weak-but significant-complex relation between CEA and DE. They are associated
      through a series of mediating relations in a multivariate model including
      alexithymia and GD. The current study supports research suggesting that child
      emotional abuse can have a negative impact on its survivors. Treatment of those
      survivors manifesting disordered eating should be holistic, as opposed to
      targeted towards specific symptoms.

PMID- 16603243
TI  - Approaches to child protection case management for cases involving people with
      disabilities.
AB  - OBJECTIVES: This exploratory study examines the delivery of child protection
      services by county child protection agencies involving cases with a family member
      with a disability. METHOD: Telephone surveys were conducted with the directors or
      their designees of 89% of the child protection agencies in a Midwestern state.
      Respondents were asked about the policies and/or procedures for approaching cases
      involving a person with a disability and the barriers and strengths agencies have
      in serving people with disabilities. RESULTS: Only 6.7% of respondents reported
      their agency had a written policy related to serving persons with a disability.
      There were 18 different approaches to serving clients with a disability within
      child protection, with the most common being informally teaming for information,
      dual case assignment, and teaming with an outside consultant. Five counties had
      specialty workers who were experts in both child protection and disability.
      Barriers reported varied between rural and non-rural counties, with the most
      important barriers being lack of resources, lack of knowledge regarding
      disabilities, systems conflicts, and rural issues, such as lack of providers and
      lack of transportation. Strengths included accessing and coordinating services,
      individualizing services, good collaboration and creativity. CONCLUSION: While
      few county agencies had any written policies, both formal and informal
      collaboration is happening at the individual level. The lack of standardization
      in providing services indicates a need for more attention to issues regarding
      disability within child protection, including more training for workers, the
      development of models of collaborative case management and the removal of
      systemic barriers.

PMID- 16603244
TI  - Fourth-generation fluoroquinolone penetration into the aqueous humor in humans.
AB  - PURPOSE: To compare the penetration and levels of the fourth-generation
      fluoroquinolones moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3%
      solution in the aqueous humor (AH) in humans after topical application with
      published levels of other available fluoroquinolones under similar dosing
      conditions. DESIGN: Prospective, randomized, double-masked clinical trial.
      PARTICIPANTS: Forty-six patients undergoing cataract extraction. METHODS:
      Patients scheduled for routine phacoemulsification and intraocular lens
      implantation were provided either moxifloxacin 0.5% ophthalmic solution (n = 22)
      or gatifloxacin 0.3% ophthalmic solution (n = 24) to use 4 times daily the day
      before surgery plus 1 drop 1 hour before the surgical entry into the anterior
      chamber on the day of surgery. This regimen simulated a realistic postoperative
      dosing schedule. Aqueous humor samples were obtained and analyzed by high
      pressure liquid chromatography. Aqueous humor fluoroquinolone concentrations were
      calculated by peak comparison with a known concentration peak for ciprofloxacin
      that was used as an internal standard. These values were compared with published
      concentrations of other available fluoroquinolones under similar dosing
      conditions. RESULTS: The mean age of the moxifloxacin 0.5% group was 67.8+/-9.7
      years, whereas that of the gatifloxacin 0.3% group was 69.9+/-8.7 years. The
      moxifloxacin AH concentration was 1.86+/-1.06 microg/ml, and that of gatifloxacin
      was 0.94+/-0.72 microg/ml. This 2-fold difference was statistically significant
      (P = 0.001). CONCLUSIONS: Aqueous humor antibiotic concentrations achieved at the
      time of cataract surgery after topical application can serve as an effective
      surrogate for what can be achieved with typical postoperative topical dosing
      (e.g., 4 times daily). Both fourth-generation fluoroquinolones achieved a greater
      AH concentration after 4 times daily dosing relative to prior-generation
      fluoroquinolones. Moxifloxacin 0.5% ophthalmic solution achieved a 2-fold higher
      aqueous humor concentration than gatifloxacin 0.3% ophthalmic solution. The
      superior penetration of moxifloxacin into the AH may be attributed partially to
      its high degree of lipophilicity, greater solubility at neutral pH, and higher
      concentration in the commercial formulation. The enhanced penetration of
      moxifloxacin 0.5% ophthalmic solution may provide better protection against
      ocular infections.

PMID- 16603245
TI  - Severe ocular injury resulting from chuna packets.
AB  - OBJECTIVE: To describe a mechanism of severe ocular alkali burns occurring as a
      result of bursting of chuna packets (edible calcium hydroxide paste), a popular
      additive to chewing tobacco in India. DESIGN: Retrospective case series.
      PARTICIPANTS: Twenty-one patients (25 eyes) who experienced ocular burns as a
      result of bursting of chuna packets. INTERVENTION: Patients were treated
      medically or with 1 or more of the following surgeries: symblepharon release,
      amniotic membrane grafting, allograft or autograft stem cell transplantation, or
      both, and large diameter lamellar keratoplasty. MAIN OUTCOME MEASURES: The main
      outcome measures were time interval between the injury and presentation,
      presenting visual acuity, grade of injury, management (medical therapy or
      surgical intervention), and final visual outcome at the last follow-up. RESULTS:
      The average age at time of injury was 8.4+/-5.5 years. The median visual acuity
      at presentation was light perception with projection. The ocular burns were grade
      4 in 23 eyes. Eight of 25 eyes were treated medically, and the rest underwent 1
      or more surgeries in the form of symblepharon release (n = 6), amniotic membrane
      grafting (n = 3), allograft or autograft stem cell transplantation (n = 6), and
      large diameter lamellar keratoplasty (n = 6). At the final follow-up (mean, 637+/
      592 days), median visual acuity was 1/60. CONCLUSIONS: Bursting of chuna packets
      can cause severe ocular alkali burns in children. These patients carry a poor
      visual prognosis with both medical and surgical therapy.

PMID- 16603246
TI  - Nephropathic cystinosis: posterior segment manifestations and effects of
      cysteamine therapy.
AB  - PURPOSE: Cystinosis is a rare autosomal recessive lysosomal storage disorder
      characterized by the intracellular accumulation of cystine. Treatment involves
      intracellular cystine depletion with oral cysteamine. A wide spectrum of ocular
      pathologic features has been associated with nephropathic cystinosis. We used the
      largest documented cohort of patients in the world to study the posterior segment
      manifestations associated with infantile nephropathic cystinosis and to determine
      retrospectively the effect of chronic oral cysteamine therapy on the frequency of
      these abnormalities. DESIGN: Cross-sectional study of a series of patients.
      PARTICIPANTS: Two hundred eight patients with infantile nephropathic cystinosis
      were studied at the National Institutes of Health between 1976 and 2004. METHODS:
      All patients underwent an ophthalmic evaluation. Patients older than 11 years
      also underwent Humphrey static perimetry, and electrophysiological testing was
      performed when possible. MAIN OUTCOME MEASURES: Visual acuity, retina findings,
      visual fields, and electroretinographic (ERG) findings. RESULTS: Pigmentary
      changes with retinal pigment epithelial mottling, seen as early as infancy, were
      the most common posterior segment manifestations. Moderate to severe constriction
      of the visual fields, as well as moderate to severe reduction of rod- and cone
      mediated ERG responses, was seen in older patients. The frequency of retinopathy
      correlated directly with time not receiving oral cysteamine therapy and inversely
      with time receiving oral cysteamine therapy. CONCLUSIONS: Infantile nephropathic
      cystinosis has posterior segment complications that can contribute to significant
      visual handicap. Early initiation of oral cysteamine therapy can reduce the
      frequency of posterior segment complications in cystinosis patients.

PMID- 16603247
TI  - Spectroscopic characterization of the ferric states of Amphitrite ornata
      dehaloperoxidase and Notomastus lobatus chloroperoxidase: His-ligated peroxidases
      with globin-like proximal and distal properties.
AB  - Amphitrite ornata dehaloperoxidase (DHP) and Notomastus lobatus chloroperoxidase
      (NCPO) catalyze the peroxide-dependent dehalogenation of halophenols and
      halogenation of phenols, respectively. Both enzymes have histidine (His) as their
      proximal heme iron ligand. Crystallographic examination of DHP revealed that it
      has a globin fold [M.W. LaCount, E. Zhang, Y.-P. Chen, K. Han, M.M. Whitton, D.E.
      Lincoln, S.A. Woodin, L. Lebioda, J. Biol. Chem. 275 (2000) 18712-18716] and
      kinetics studies established that ferric DHP is the active state [R.L. Osborne,
      L.O. Taylor, K. Han, B. Ely, J.H. Dawson, Biochem. Biophys. Res. Commun. 324
      (2004) 1194-1198]. NCPO likely has these same properties. Previous work with His
      ligated heme proteins has revealed characteristic spectral distinctions between
      dioxygen binding globins and peroxide-activating peroxidases. Since DHP, and
      likely NCPO, is a peroxide-activating globin, we have sought to determine in the
      present investigation whether the ferric resting states of these two novel heme
      containing enzymes are myoglobin-like or peroxidase-like. To do so, we have
      examined their exogenous ligand-free ferric states as well as their azide,
      imidazole and NO bound ferric adducts (and ferrous-NO complexes) with UV-Visible
      absorption and magnetic circular dichroism spectroscopy. We have also compared
      each derivative to the analogous states of horse heart myoglobin (Mb) and
      horseradish peroxidase (HRP). The spectra observed for parallel forms of DHP and
      NCPO are virtually identical to each other as well as to the spectra of the same
      Mb states, while being less similar to the spectra of corresponding HRP
      derivatives. From these data, we conclude that exogenous ligand-free ferric DHP
      and NCPO are six-coordinate with water and neutral His as ligands. This
      coordination structure is distinctly different from the ferric resting state of
      His-ligated peroxidases and indicates that DHP and NCPO do not activate bound
      peroxide through a mechanism dependent on a push effect imparted by a partially
      ionized proximal His as proposed for typical heme peroxidases.

PMID- 16603248
TI  - Photogeneration of titanium(III) from titanium(IV) citrate in aqueous solution.
AB  - Current interest in the biochemistry of Ti(IV) arises from its widespread use in
      white pigments and its potential in therapeutic agents. Citrate is known to form
      strong complexes with Ti(IV). We show here that Ti(III) citrate is generated in a
      facile manner and in good yield by the action of UV radiation on Ti(IV) citrate
      in aqueous solution. The Ti(III)-citrate species formed was isolated and
      characterised by UV-Visible spectroscopy, showing an absorption at 547 nm
      (epsilon=100 M(-1)cm(-1)), and by electron paramagnetic resonance (EPR)
      spectroscopy giving a resonance at g=1.949 (linewidth=60G) . An X-ray structure
      of the parent Ti(IV) complex in the form
      [TiNa(3)(C(6)H(6)O(7))(2)(C(6)H(5)O(7))(H(2)O)(6.8)].2H(2)O is reported along
      with a study of the reaction of Ti(IV)-citrate with N,N-ethylenebis(o
      hydroxytoluene)glycine (EHTG), which was more rapid than those of other related
      Ti(IV) complexes.

PMID- 16603249
TI  - From bench to bedside--preclinical and early clinical development of the
      anticancer agent indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]
      (KP1019 or FFC14A).
AB  - Indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019 or FFC14A)
      is just the second ruthenium-based anticancer agent after NAMI-A which was
      developed to the stage of clinical trials. Important steps in the mode of action
      of KP1019 are thought to be the binding to the serum protein transferrin and the
      transport into the cell via the transferrin pathway. Additionally, the selective
      activation by reduction in the tumor might contribute to the low side effects
      observed in in vivo studies. Apoptosis is induced at non-toxic levels via the
      mitochondrial pathway. These features distinguish it from the established
      platinum anticancer drugs and suggest that different types of cancer might be
      treatable with this drug. Indeed, promising activity against certain types of
      tumors, which are not successfully treatable with cisplatin, and only a very low
      incidence of acquired resistance has been observed in in vitro and in vivo
      studies. Recently, a clinical phase I trial was finished in which none of the
      treated patients experienced serious side effects, while disease stabilization in
      five of six evaluable patients was achieved. In this review, the preclinical and
      early clinical development of KP1019 - from bench to bedside - is recapitulated.

PMID- 16603250
TI  - An unusual case of deep candidosis presenting as an infiltrating tumour of the
      chest wall.
AB  - A 45-year-old man presented with an unclear rapidly growing, infiltrating tumour
      of the anterior chest wall. Biopsies were non-specific, serologies remained
      unremarkable. Shortly after admission the patient developed blurred vision.
      Ophthalmoscopical findings were typical of candida endophthalmitis. Meanwhile,
      the tumour continued to grow. When it was resected, hyphae of Candida albicans
      were yielded from the tissue revealing it as a manifestation of deep candidosis.
      The infection had probably been acquired endogenously during abdominal surgery
      for early stage rectal carcinoma which the patient had undergone several weeks
      ago and which was followed by an unexplained fever. Interestingly, deep
      candidosis presenting as an infiltrating tumour of the anterior chest wall often
      combined with candidal endophthalmitis has been described almost exclusively in
      intravenous drug users after the injection of contaminated heroin [Collignon PJ,
      Sorrell TC. Disseminated candidiasis: evidence of a distinctive syndrome in
      heroin abusers. Br Med J (Clin Res Ed) 1983;287(6396):861-2; Dupont B, Drouhet E.
      Cutaneous, ocular, and osteoarticular candidiasis in heroin addicts: new clinical
      and therapeutic aspects in 38 patients. J Infect Dis 1985;152(3):577-91; Bisbe J,
      Miro JM, Latorre X, Moreno A, Mallolas J, Gatell JM, et al. Disseminated
      candidiasis in addicts who use brown heroin: report of 83 cases and review. Clin
      Infect Dis 1992;15(6):910-23.]. Why the tumours only develop on the anterior
      thoracic wall is unknown. To our knowledge this is the first case described in
      literature in which endogenously acquired deep candidosis manifested as an
      infiltrating tumour in a patient who was neither immunosuppressed nor had a
      history of intravenous drug use.

PMID- 16603251
TI  - Cerebral venous thrombosis as a complication of leptospirosis.
AB  - Leptospirosis is an acute infectious disease caused by a spirochete of the
      leptospira gender and it is characterized by severe vasculitis. It is not common
      for leptospirosis to present as a primary neurological disease. On the other
      hand, no study has been reported on the progression of cerebral venous thrombosis
      (CVT) in patients with leptospirosis so far. This is the first case reported
      which shows CVT as a complication after the leptospirosis infection. An acutely
      developed leptospirosis and post-infectious CVT in a 21-year-old soldier is
      described here.

PMID- 16603252
TI  - Mitotic kinases: the key to duplication, segregation, and cytokinesis errors,
      chromosomal instability, and oncogenesis.
AB  - Chromosomal instability (CIN) and aneuploidy are commonly observed in the vast
      majority of human solid tumors and in many hematological malignancies. These
      features are considered defining characteristics of human breast, bladder and
      kidney cancers since they markedly exceed a 50% aneuploidy frequency. The
      detection of persistent mitotic kinase over-expression, particularly the Aurora
      family, and centrosome amplification in precursor/pre-malignant stages, strongly
      implicate these molecular changes in precipitating the aneuploidy seen in many
      human neoplasms. Mitotic spindle checkpoint defects may also lead to aneuploid
      tumors. However, the sustained over-expression and activity of various members of
      the mitotic kinase families, including Aurora (Aur) (A, B, C), Polo-like (Plk1
      4), and Nek (NIMA1-11) in diverse human tumors strongly indicate that these
      entities are intimately involved in the development of errors in centrosome
      duplication, chromosome segregation, and cytokinesis. Mitotic kinases have also
      been implicated in regulating the centrosome cycle, spindle checkpoint and
      microtubule-kinetochore attachment, spindle assembly, and chromosome
      condensation. These mitotic kinases are modulated by de-novo synthesis, stability
      factors, phosphorylation, and ubiquitin-dependent proteolysis. They, in turn,
      phosphorylate a myriad of centrosomal/mitotic protein substrates, and have the
      ability to behave as oncogenes (i.e. Aur-A, Plk-1), providing a compelling link
      between errors in mitosis and oncogenic processes. The recent development of
      selective small molecule inhibitors of Aurora kinases, in particular, will
      provide useful tools to ascertain more precisely their role in cancer
      development. Potent inhibitors of mitotic kinases, when fully developed, have the
      promise to be effective agents against tumor growth, and possibly, tumor
      prevention as well.

PMID- 16603253
TI  - Adhesion of Borrelia garinii to neuronal cells is mediated by the interaction of
      OspA with proteoglycans.
AB  - To study pathogenic mechanisms of Lyme meningoradiculitis, dorsal root ganglia
      (DRG) cells and two neuronal cell lines (B50, SH-SY5Y) were incubated with
      Borrelia garinii, the Borrelia species most frequently isolated from CSF of Lyme
      neuroborreliosis patients in Europe. We demonstrated that (I) OspA-positive B.
      garinii adhere to neuronal cells, (II) Borrelia adhesion can be blocked by a
      monoclonal antibody against OspA, (III) preincubation with proteoglycans
      interferes with the adhesion process and (IV) rOspA directly binds to the
      proteoglycans. This indicates that both OspA and the cell bound proteoglycans are
      involved in the attachment of B. garinii to neuronal cells.

PMID- 16603254
TI  - Serotonin and dopamine in the parabrachial nucleus of rats during conditioned
      taste aversion learning.
AB  - A microdialysis technique was used to monitor changes in serotonin (5-HT), 5
      hydroxyindole acetic acid (5-HIAA) and dopamine (DA) in the extracellular space
      of the parabrachial nucleus (PBN) of rats to estimate the contribution of these
      neurotransmitter systems to the acquisition of conditioned taste aversion (CTA).
      A significant (280%) enhancement of 5-HT was found immediately after saccharin
      drinking (CS). I.p. injection of unconditioned stimulus LiCl alone (after water
      drinking) also increased level of 5-HT (200%). However, when saccharin intake was
      followed by injection of LiCl (CS-US pairing), no change in 5-HT was observed. 5
      HIAA and DA were unaffected by any of the above treatments. Thus in spite of
      elevation of 5-HT in PBN following saccharin consumption alone (CS) or LiCl
      administration alone (US) no changes in 5-HT occurred after pairing of both
      stimuli (CS-US). Our work demonstrates that participation of 5-HT in acquisition
      of CTA appears to be unlikely, and also DA appears not to be engaged in this
      acquisition at all. At the level of the PBN 5-HT participates mainly in CS and/or
      US stimuli processing, where this phenomenon has close relationship to other
      important physiological mechanisms, involved in behavioral control. Such as
      anxiety, alimentation intake.

PMID- 16603255
TI  - Investigation of micronuclei and other nuclear abnormalities in peripheral blood
      and kidney of marine fish treated with crude oil.
AB  - The induction of micronuclei and other nuclear abnormalities (nuclear buds, bi
      nucleated and fragmented-apoptotic cells) was analyzed in the erythrocytes of
      peripheral blood and cephalic kidney of turbot (Scophthalmus maximus) and
      Atlantic cod (Gadus morua), treated with crude oil (Statfjord B, Norway) and with
      nonylphenol. Significant increase in MN was observed in turbot kidney and blood
      after exposure to 30 ppb of nonylphenol, 0.5 ppm of oil, and after co-exposure to
      0.5 ppm of oil spiked with additional mixture of alkylphenols and PAHs (P varied
      between 0.0054 and <0.0001). The induction of micronuclei was observed only in
      cod kidney after exposure to spiked oil (P=0.0317). Significant inter-specific
      differences after the exposure to 0.5 ppm of oil (P=0.0385) and after treatment
      with spiked oil (P=0.0067) were observed. In turbot cephalic kidney, the elevated
      levels of bi-nucleated cells were observed in all treatment groups (P values
      varied in a range from 0.05 to 0.0025) while the increase in cells with nuclear
      buds was noted after the exposure to 0.5 ppm of oil (P=0.05). The fragmented
      apoptotic cells appeared after the exposure to nonylphenol (P=0.0039) and to
      spiked oil (P<0.0001). In turbot blood, only the significant induction in nuclear
      buds was detected. Statistically significant inter-tissue differences were found
      only in the induction of fragmented-apoptotic cells after the exposure to
      nonylphenol and to spiked oil.

PMID- 16603256
TI  - Protein responses in blue mussels (Mytilus edulis) exposed to organic pollutants:
      a combined CYP-antibody/proteomic approach.
AB  - Polyclonal antibodies were raised against highly conserved, trans-metazoan
      sequences of cytochrome P450 (CYP) families 2 and 4 and used to investigate
      responses in the common blue mussel (Mytilus edulis) exposed to various organic
      contaminants. The results were evaluated by means of cross-reacting proteins on
      Western blots of both one- and two-dimensional electrophoresis gels, and by
      scanning spectroscopy measurements of total CYP content. Furthermore, a proteomic
      approach was applied aimed at elucidating exposure-related protein changes in a
      more general term. Identities of isolated proteins were searched by means of
      peptide mass fingerprints obtained from MALDI-TOF MS analyses. The results
      demonstrated that both antibodies rendered several cross-reactive bands when
      probed on Western blots. The most obvious cross-reaction of the CYP2 antibody was
      with a strongly expressed protein of size approximately 57kDa, pI 4.5-4.6,
      whereas the CYP4 antibody cross-reacted with a protein of size approximately
      55kDa, pI 5.6. However, expression of cross-reacting proteins did not change as a
      result of the exposures, and resulted only in small and insignificant
      fluctuations in total CYP content. As a contrast, silver-stained 2DE gels showed
      that several microsomal proteins were affected in individuals exposed to
      diallylphthalate as well as crude oil, with and without a spike of alkylphenols
      and PAHs. Mass spectrometry based analyses of excised, trypsin-digested spots did
      so far not decipher the identities of the proteins affected by the exposures, nor
      of those cross-reacting with CYP2 and CYP4 antibodies. This study has underlined
      the power of the proteomic approach in environmental toxicology, although protein
      identification was not successful. The missing identities of the proteins cross
      reacting with the CYP2- and CYP4-antibodies does not enable a clear conclusion as
      to whether or not these peptides actually represent CYP iso-enzymes.

PMID- 16603257
TI  - Isolation and characterization of Schistosoma mansoni constitutive androstane
      receptor.
AB  - Full length cDNA clones encoding a Schistosoma mansoni homologue of vertebrate
      CAR/PXR/VDR group nuclear receptor, termed SmCAR were isolated from screening a
      S. mansoni adult worm cDNA library. SmCAR is a 702 amino acid protein which
      retains a typical domain organization of nuclear receptor superfamily members. A
      homology search demonstrated that SmCAR exhibits the highest homology with mouse
      constitutive androstane receptor (CAR). Like its orthologues from invertebrates,
      SmCAR contains a P box sequence of ESCKA in the DNA binding domain. The P box is
      important in determining the DNA binding specificity for nuclear receptors. SmCAR
      mRNA is expressed in every stage of S. mansoni life cycle with an elevated
      expression level in egg and cercaria stages. Two forms (78 and 81 kDa) of SmCAR
      protein were detected in schistosome worm extract by Western blot analysis. SmCAR
      protein was demonstrated to be widely distributed in adult worms by
      immunolocalization studies, being found in the subtegument in both male and
      female worms and in the ovaries, vitellaria and eggs in female worms. In vitro
      DNA binding assays demonstrated that SmCAR binds to the hsp27 ecdysone response
      element (EcRE) as well as schistosome p14 gene upstream region. The AGTGCA half
      site is essential for binding of SmCAR to the p14 gene upstream region.
      Therefore, AGTGCA probably serves as a high affinity binding half site for ESCKA
      containing nuclear receptors.

PMID- 16603258
TI  - Characterization of three Rop GTPase genes of alfalfa (Medicago sativa L.).
AB  - Three cDNA clones coding for Medicago sativa Rop GTPases have been isolated. The
      represented genes could be assigned to various linkage groups by genetic mapping.
      They were expressed in all investigated plant organs, although at different
      level. Relative gene expression patterns in response to Sinorhizobium infection
      of roots as well as during somatic embryogenesis indicated their differential
      participation in these processes. DNA sequences coding for altogether six
      different Medicago sp. Rop GTPases could be identified in sequence databases.
      Based on their homology to each other and to their Arabidopsis counterparts, a
      unified nomenclature is suggested for Medicago Rop GTPases.

PMID- 16603259
TI  - Physical and functional interactions of Arabidopsis ADA2 transcriptional
      coactivator proteins with the acetyltransferase GCN5 and with the cold-induced
      transcription factor CBF1.
AB  - The Arabidopsis GCN5, ADA2a and ADA2b proteins are homologs of components of
      several yeast and animal transcriptional coactivator complexes. Previous work has
      implicated these plant coactivator proteins in the stimulation of cold-regulated
      gene expression by the transcriptional activator protein CBF1. Surprisingly,
      protein interaction studies demonstrate that the DNA-binding domain of CBF1 (and
      of a related protein, TINY), rather than its transcriptional activation domain,
      can bind directly to the Arabidopsis ADA2 proteins. The ADA2a and ADA2b proteins
      can also bind directly to GCN5 through their N-terminal regions (comparable to a
      region previously defined in yeast Ada2) and through previously unmapped regions
      in the middle of the ADA2 proteins, which bind to the HAT domain of GCN5. The
      ADA2 proteins enhance the ability of GCN5 to acetylate histones in vitro and
      enable GCN5 to acetylate nucleosomal histones. Moreover, GCN5 can acetylate the
      ADA2 proteins at a motif unique to the plant homologs and absent from fungal and
      animal homologs. We speculate that this modification may represent a novel
      autoregulatory mechanism for the plant SAGA-like transcriptional coactivator
      complexes.

PMID- 16603260
TI  - Protein kinase A-regulated membrane trafficking of a green fluorescent protein
      aquaporin 5 chimera in MDCK cells.
AB  - The green fluorescent protein (GFP) of the jellyfish, Aeqorea victoria, was used
      as an autofluorescent tag to track the trafficking of aquaporin 5 (AQP5), an
      exocrine gland-type water channel. Two groups of chimeric proteins were
      constructed; one in which GFP was fused to the amino-terminus of AQP5 (GFP-AQP5)
      and the other, in which it was fused to the carboxyl terminus of it (AQP5-GFP).
      In each group, 2 chimeras were produced, a wild-type AQP5 with its normal
      sequence and a mutant AQP5 having a mutated amino acid at 259, i.e., GFP-AQP5
      T259A and AQP5-GFP-T259A. They were used to transfect Madin-Darby canine kidney
      (MDCK) cells. The GFP-AQP5 chimera was localized in the intracellular vesicles,
      which trafficked to the plasma membrane in response to N(6), 2'-O
      dibutyryladenosine 3', 5'-cyclic monophosphate (dbcAMP). Membrane trafficking was
      inhibited by N-[2-(p-bromocinnamylamino)ethyl]-5-isoquimolinesulfonamide (H-89)
      but not by palmitoyl-dl-carnitine chloride (PCC). In contrast, the AQP5-GFP
      chimera expressed in MDCK cells was localized constitutively on the plasma
      membrane. The cellular localization of the latter chimera was not affected by
      stimulation with dbcAMP in the presence or absence of H-89 or PCC. Replacement of
      Thr-259 with Ala-259 did not affect the dbcAMP-induced translocation of the
      chimeric protein, suggesting that phosphorylation of Thr-259 was not necessary
      for AQP5 trafficking under the present experimental conditions. Thus, the GFP
      AQP5 chimera will be a useful tool to study AQP5 trafficking in vitro, whereas
      the constitutive membrane localization of the AQP5-GFP chimera suggests the
      importance of the carboxyl terminus of the AQP5 protein for its sorting, whether
      it is translocated to intracellular vesicles or to the plasma membrane.

PMID- 16603261
TI  - Nek1 shares structural and functional similarities with NIMA kinase.
AB  - The Aspergillus NIMA serine/threonine kinase plays a pivotal role in controlling
      entrance into mitosis. A major function attributed to NIMA is the induction of
      chromatin condensation. We show here that the founder murine NIMA-related kinase,
      Nek1, is larger than previously reported, and that the full-length protein
      conserves the structural hallmarks of NIMA. Even though Nek1 bears two classical
      nuclear localization signals (NLS), the endogenous protein localizes to the
      cytoplasm. Ectopic overexpression of various Nek1 constructs suggests that the C
      terminus of Nek1 bears cytoplasmic localization signal(s). Overexpression of
      nuclear constructs of Nek1 resulted in abnormal chromatin condensation, with the
      DNA mainly confined to the periphery of the nucleus. Advanced condensation
      phenotype was associated with nuclear pore complex dispersal. The condensation
      was not accompanied by up-regulation of mitotic or apoptotic markers. A similar
      phenotype has been described following NIMA overexpression, strengthening the
      notion that the mammalian Nek1 kinase has functional similarity to NIMA.

PMID- 16603262
TI  - The Venus figurines.

PMID- 16603263
TI  - Intracardiac echocardiography in monitoring atrial septal defect percutaneous
      closure: initial experience in an adult laboratory.
AB  - Two cases of percutaneous closure of atrial septal defect and patent foramen
      ovale with intracardiac echo monitoring are described. Intracardiac
      echocardiography was compared to contemporary TOE with full data concordance. The
      inherent implications and limitations of this new method are discussed.

PMID- 16603264
TI  - Floating thrombus arising from left sinus of Valsalva induced intermittent
      occlusion of left coronary artery and caused cardiogenic shock.

PMID- 16603265
TI  - Detection of Bland-White-Garland Syndrome by multislice computed tomography in an
      elderly patient.

PMID- 16603266
TI  - Ventricular tachycardia in an ice-hockey player after a blunt chest trauma.
AB  - A case of a professional ice-hockey with a blunt chest trauma is presented. A
      year after the first cardiac evaluation, he experienced sustained ventricular
      tachycardia after another slight chest trauma. An implantable cardioverter
      defibrillator was implanted. The pathophysiological background of tachycardias
      after a blunt chest trauma and its management are discussed.

PMID- 16603267
TI  - Assessing the potential of regions of the nuclear and mitochondrial genome to
      develop a "molecular tool box" for the detection and characterization of
      Phytophthora species.
AB  - Four different intergenic regions of mitochondrial DNA (mt-IGS), a fragment of
      the intergenic spacer (IGS) region of the rDNA (rDNA-IGS), and a fragment of the
      ras-related protein (Ypt1) gene were amplified and sequenced from a panel of 31
      Phytophthora species representing the most significant forest pathogens and the
      breadth of diversity in the genus. Over 80 kbp of novel sequences were generated
      and alignments showed very variable (introns and non-coding regions) as well as
      conserved coding regions. The mitochondrial DNA regions had an AT/GC ratio
      ranging from 67.2 to 89.0% and were appropriate for diagnostic development and
      phylogeographic analysis. The IGS fragment was less variable but still
      appropriate to discriminate amongst some important forest pathogens. The introns
      of the Ypt1 gene were sufficiently polymorphic for the development of molecular
      markers for almost all Phytophthora species, with more conserved flanking coding
      regions appropriate for the design of Phytophthora genus-specific primers. In
      general, phylogenetic analysis of the sequence alignments grouped species in
      clades that matched those based on the ITS regions of the rDNA. In many cases the
      resolution was improved over ITS but in other cases sequences were too variable
      to align accurately and yielded phylograms inconsistent with other data. Key
      studies on the intraspecific variation and primer specificity remain. However the
      research has already yielded an enormous dataset for the identification,
      detection and study of the molecular evolution of Phytophthora species.

PMID- 16603268
TI  - Influence of packaging on spoilage yeast population in minimally processed orange
      slices.
AB  - The yeast population of minimally processed orange slices, packaged both in
      normal and modified atmosphere and with films of different permeabilities, was
      studied in order to set up the most suitable packaging conditions. Modified
      atmosphere resulted in a fermentative association of yeast strains, with the
      dominance of Saccharomyces cerevisiae strains. In samples packaged in normal
      atmosphere isolated strains have been mainly identified as Rhodotorula spp.

PMID- 16603269
TI  - Reliable amplification method for bacterial RNA.
AB  - DNA microarray technology has been increasingly applied for studies of clinical
      samples. Frequently, RNA probes from clinical samples are available in limited
      amounts. We describe a reliable amplification method for bacterial RNA. We
      verified this method on mycobacterial RNA applying mycobacterial genome-directed
      primers (mtGDPs). Glass slide-based oligoarrays were employed to assess the
      quality of the amplification method. We observed a relatively small bias in
      amplified RNA pool when compared to the unamplified one. Up to 1000-fold linear
      RNA amplification in a single amplification round was obtained. To our knowledge,
      this study describes the first amplification method for mycobacterial RNA.

PMID- 16603270
TI  - Identification of the bacterial superoxide dismutase (SodM) as plant-inducible
      elicitor of an oxidative burst reaction in tobacco cell suspension cultures.
AB  - Three of the most abundant proteins (OmpW, MopB and SodM) of the extracellular
      proteome of Xanthomonas campestris pv. campestris were analysed in a luminol
      based oxidative burst assay to identify novel pathogen-associated molecular
      patterns (PAMP). Tobacco cell suspension cultures were used as a model system to
      monitor elicitor induced plant defence reaction. The candidate proteins were
      isolated from two-dimensional gels prior to application to the oxidative burst
      assay. The superoxide dismutase (SodM) was the only isolated protein that could
      elicit a notable hydrogen peroxide (H2O2) production in tobacco cell cultures
      indicating the initiation of plant defence. An alignment of the SodM sequences
      from X. campestris pv. campestris and Escherichia coli revealed 55.7% identity
      and 29% of the sequence were substitutions for amino acids with similar physico
      chemical properties. By using a commercially available purified E. coli derived
      SodM preparation, it was possible to show that the amino acid sequence of this
      protein is responsible for the elicitation of an oxidative burst reaction in the
      tobacco cell culture model. This suggests that the bacterial superoxide dismutase
      is a novel pathogen-associated molecular pattern. The minimal elicitor active
      sequence, however, is still elusive.

PMID- 16603271
TI  - Collaborative study to evaluate a new ELISA test to monitor the effectiveness of
      rabies vaccination in domestic carnivores.
AB  - To prevent any introduction of rabies, many rabies-free countries have adopted a
      scheme requiring the rabies vaccination of pets associated with a serological
      test. FAVN test and RFFIT are the current OIE prescribed techniques to perform
      this assay. A qualitative indirect ELISA (Serelisa) test has been recently
      described as a screening test to monitor the effectiveness of rabies vaccination
      of pets. A lack of sensitivity requires ELISA negative samples to be retested
      using an OIE confirmatory test. This raised the question whether this new test
      could be reasonably proposed as an alternative tool in the context of
      international trades of pets. The Community Reference Institute of Nancy
      organized a short trial to answer this question. In this study, 16 laboratories
      tested a panel of their own samples with FAVN test/RFFIT and the Serelisa. The
      comparison of results revealed that the performance of the Serelisa is highly
      heterogeneous. A lack of sensitivity was detected in 50% of participants, when
      25% of laboratories obtained a significant rate of false positive results. This
      last point questions the pertinence of using the Serelisa in the context of
      international trades by preventing any movements of insufficiently or non
      protected animals.

PMID- 16603272
TI  - Synthesis and characterization of novel poly(ethylene glycol)-lipid conjugates
      suitable for use in drug delivery.
AB  - Liposomal formulations have been used to encapsulate and deliver a wide variety
      of therapeutic and diagnostic agents. Their circulation can be prolonged by the
      addition of neutral, hydrophilic polymers such as poly(ethylene glycol) (PEG) to
      the outer surface. An extended circulation lifetime allows them to take advantage
      of the enhanced permeability and retention effect (EPR), resulting in increased
      delivery to target sites. Incorporation of PEG also prevents aggregation and aids
      in the formation of uniform, small mono-disperse particles. This is often
      accomplished with the use of PEG-lipid conjugates, PEG molecules with a
      hydrophobic domain to anchor them into the liposomal bilayer upon formulation.
      Here we present data showing that some commonly used PEG-lipids are chemically
      unstable due to the presence of carboxylic ester bonds. This instability limits
      their utility in aqueous environments common to many liposomal preparations. To
      address this problem, we designed and synthesized three alternative PEG-lipids.
      Using SPLP (PEG-stabilized liposomal vesicles encapsulating plasmid DNA) as a
      model system, we investigated the properties of the novel PEG-lipids. An
      accelerated stability study was conducted at 37 degrees C for 42 days to confirm
      chemical stability and an in vivo model was used to assess the pharmacokinetics,
      toxicity and activity of the SPLP. We show that the novel PEG-lipids are more
      stable in liposomal formulation, less toxic upon systemic administration, and
      accordingly, are suitable replacements for the PEG-lipids described previously.

PMID- 16603273
TI  - FtsZ may have dual roles in the filamentous cyanobacterium Nostoc/Anabaena sp.
      strain PCC 7120.
AB  - The cellular and subcellular localization of FtsZ, a bacterial cell division
      protein, were investigated in vegetative cells of the filamentous cyanobacterium
      Nostoc/Anabaena sp. strain PCC 7120. We show by using immunogold-transmission
      electron microscopy that FtsZ forms a ring structure in a filamentous
      cyanobacterium, similar to observations in unicellular bacteria and chloroplasts.
      This finding, that the FtsZ in a filamentous cyanobacterium accumulates at the
      growing edge of the division septa leading to the formation of the typical
      prokaryotic Z-ring arrangement, is novel. Moreover, an apparent cytoplasmic
      distribution of FtsZ occurred in vegetative cells. During the transition of
      vegetative cells into terminally differentiated heterocysts the cytoplasmic FtsZ
      levels decreased substantially. These findings suggest a conserved function of
      FtsZ among prokaryotes, including filamentous cyanobacteria with cell
      differentiation capacity, and possibly a role of FtsZ as a cytoskeletal component
      in the cytoplasm.

PMID- 16603274
TI  - Isolation of an osmotin-like protein gene from strawberry and analysis of the
      response of this gene to abiotic stresses.
AB  - A strawberry genomic clone containing an osmotin-like protein (OLP) gene,
      designated FaOLP2, was isolated and sequenced. FaOLP2 is predicted to encode a
      precursor protein of 229 amino acid residues, and its sequence shares high
      degrees of homology with a number of other OLPs. Genomic DNA hybridization
      analysis indicated that FaOLP2 represents a multi-gene family. The expression of
      FaOP2 in different strawberry organs was analyzed using real-time PCR. The
      results showed that FaOLP2 expressed at different levels in leaves, crowns,
      roots, green fruits and ripe red fruits. In addition, the expression of FaOLP2
      under different abiotic stresses was analyzed at different time points. All of
      the three tested abiotic stimuli, abscisic acid, salicylic acid and mechanical
      wounding, triggered a significant induction of FaOLP2 within 2-6h post-treatment.
      Moreover, FaOLP2 was more prominently induced by salicylic acid than by abscisic
      acid or mechanical wounding. The positive responses of FaOLP2 to the three
      abiotic stimuli suggested that strawberry FaOLP2 may help to protect against
      osmotic-related environmental stresses and that it may also be involved in plant
      defense system against pathogens.

PMID- 16603275
TI  - [AntiTNFalpha-induced systemic vasculitis and autoimmune disorders].

PMID- 16603276
TI  - Higher education provision for professionals working with people with dementia: a
      scoping exercise.
AB  - This paper reports on the first national UK survey of higher education provision
      related to dementia care. A questionnaire was distributed to lecturers in Higher
      Education Institutions (HEIs) in England and Wales seeking information about the
      amount of coverage of dementia within their pre-registration and pre-qualifying
      courses for health and social care professionals, and continuing professional
      development (CPD) courses on dementia care. Information was sought regarding the
      content of courses, and their relation to a published "dementia curriculum"
      [Pulsford et al., The contribution of higher education to dementia care, Journal
      of Dementia Care 11(4) (2003) 27-29]. Results show that coverage of dementia
      within the mental health branch of pre-registration nursing programmes is very
      variable, and may be related to the presence of an experienced and committed
      lecturer within the HEI. Coverage of dementia on adult branch programmes is
      limited, and sometimes non-existent, despite reported deficits in the ability of
      general nurses to work effectively with people with dementia. Occupational
      Therapists and Social Workers receive similar input to adult branch nurses. CPD
      courses are provided by around 70% of HEIs overall, but there is a shortage of
      specialised diploma and degree level courses on dementia care. Most areas of the
      dementia curriculum are covered in both pre-registration and CPD courses, but
      culture and diversity, young onset dementia, and physical health care may be less
      well addressed. Recommendations are made for developing higher education
      provision for professionals working with this group of people.

PMID- 16603277
TI  - Safety and efficacy of the oral rabies vaccine SAG2 in raccoon dogs.
AB  - Oral vaccination programmes in several rabies-infected countries from Northern
      and Eastern Europe should not be restricted to foxes but should target raccoon
      dogs as well. The safety, immunogenicity and efficacy of Rabigen SAG2 bait was
      evaluated in raccoon dogs. Safety of SAG2 was demonstrated after direct
      instillation (n = 5) or ingestion of a bait (n = 5) using a quantity of virus at
      least 10 times superior to the field dose. All animals seroconverted and remained
      healthy. Raccoon dogs were vaccinated by SAG2 bait ingestion and unvaccinated
      raccoon dogs were kept as controls. More than 6 months after oral vaccination,
      all animals were challenged with a highly virulent street rabies virus. All 28
      vaccinated animals developed high rabies neutralizing antibody titres. After
      virulent challenge, all 11 controls succumbed to rabies, whereas all 28
      vaccinates survived.

PMID- 16603278
TI  - Ethical analysis of HPV vaccine policy options.
AB  - Vaccines against human papillomavirus (HPV) may soon be licensed. In contrast to
      most vaccine-preventable diseases, which are transmitted by air or casual
      contact, HPV is primarily transmitted by sexual contact. An analysis that applies
      ethical theories, such as utilitarianism, rule of double effect, and principlism,
      is needed for policy considerations. These analyses reveal that HPV vaccination
      can be recommended universally, including at ages 11-12 years. However, given
      concerns for autonomy, justice, as not all persons are at risk, and non
      maleficence, HPV vaccine should not be mandated for school entry. Economic
      justice indicates a need to provide vaccination for the disadvantaged.

PMID- 16603279
TI  - Enteric infections and the vaccines to counter them: future directions.
AB  - While it is well-recognized that diarrheal diseases remain the second most
      frequent cause of mortality among children <60 months of age in the developing
      world, there is nevertheless a need to obtain more precise mortality and
      hospitalization burden data in populations living in the world's least developed
      areas. There is also a glaring need to obtain robust etiology data in relation to
      the different diarrheal disease clinical syndromes, including serotypes of
      Shigella and antigenic types of ETEC. Because of the poor uptake of the new
      typhoid and cholera vaccines licensed since 1985, it will be important to create
      reliable, long-term demand for the next generation of enteric vaccines, including
      new rotavirus, Shigella and ETEC vaccines. The first priority is to get
      individual vaccines licensed. Post-licensure, it will then be simpler to
      investigate the clinical acceptability, immunogenicity and effectiveness of
      various combinations of the individual licensed enteric vaccines. The extensive
      gut mucosal surface with its many sites for induction of immune responses make it
      likely that co-administrations will be successful. Partnerships of public and
      private agencies in the developing and the industrialized world will have to be
      forged to create a reliable demand for new enteric vaccines and to assure
      adequate, sustained supplies of affordable products. Systematic implementation
      programs will have to be created in the least developed, high burden, high
      mortality countries to deliver enteric vaccines and to document their impact
      after introduction.

PMID- 16603280
TI  - Protection induced in mice against a lethal orthopox virus by the Lister strain
      of vaccinia virus and modified vaccinia virus Ankara (MVA).
AB  - The Lister (Elstree) strain of vaccinia virus, used in Israel for vaccination
      against smallpox, was studied in tissue cultures and in a mouse model. The virus
      failed to reach the brain of the mice when inoculated intranasally at a dose of
      500,000 plaque forming units, but was lethal for 50% of them, when injected
      intracranially. Lower doses of virus injected intracranially caused some weight
      loss initially, but later the mice completely recovered. Modified vaccinia virus
      Ankara (MVA), when infected intranasally, did not spread beyond the lungs to
      other organs of the mice. Even when the mice were inoculated with MVA
      intracranially, they were not affected. Significant protection against a lethal
      dose of an orthopoxvirus was obtained in mice following immunization with the
      Lister strain, while larger doses and repeated vaccination procedure, were
      required with MVA. The Lister virus stock applied in Israel, was found to be
      heterogeneous in its plaque morphology. Two variants isolated from it, showed
      significant attenuation for mice, when inoculated intranasally and
      intracranially, as compared to a third variant and to the unpurified stock of the
      virus.

PMID- 16603281
TI  - Re: Wood GD, Inion biodegradable plates: the first century. Br J Oral Maxillofac
      Surg 2006;44:38-41.

PMID- 16603282
TI  - Women's experiences of intense fear related to childbirth investigated in a
      Swedish qualitative study.
AB  - OBJECTIVES: To investigate and describe how intense fear related to childbirth is
      experienced, dealt with and communicated from the perspective of the women
      themselves. DESIGN: Qualitative interviews analysed by a grounded theory
      approach. SETTING: The study was conducted in a mid-sized city in the northern
      part of Sweden. PARTICIPANTS: A purposeful sample of 20 women, aged 24-41 with
      experiences of intense fear related to childbirth. FINDINGS: The experience of
      fear was described in relation to 'manifestations', 'time and fluctuation' and
      'judgements according to perceptions of self and others'. Ways of dealing with
      the fears could be divided into the approaches of 'evading', 'processing' and
      'seeking help'. These were often used in parallel and as exchangeable depending
      on which approach seemed to be most effective to a particular situation. Although
      some informants indicated that talking through their fears had helped them, all
      women underlined that talking about the fear was not an easy thing to do.
      'Preconditions' for being able to disclose their fears often concerned the
      interest and behaviour of antenatal health-care professionals, and an
      understanding midwife was described as crucial. KEY CONCLUSIONS AND IMPLICATIONS
      FOR PRACTICE: The findings suggest that antenatal health-care professionals need
      further training in how to meet and support women with intense fear related to
      childbirth. Such training should include how to uncover and counter socially
      constructed norms and expectations about what pregnant women should feel in
      relation to childbirth.

PMID- 16603283
TI  - Swedish women's experiences of doula support during childbirth.
AB  - OBJECTIVE: to describe women's experiences of having a doula present during
      childbirth. DESIGN AND SETTING: a qualitative study with a phenomenological
      approach in two large Swedish cities. Data were collected via open-ended taped
      interviews 1-2 months after childbirth. The analysis of the text of transcripts
      included search for meaning units sorted into clusters for a final expression of
      the essential structure of the phenomenon. DATA: interviews from 10 women aged
      between 25 and 35 years, both primiparous and multiparous. FINDINGS: women's
      needs during childbirth were described in a metaphor, as a puzzle consisting of
      different pieces where the doula was the necessary missing piece. She was a
      mainstay functioning as an experienced adviser, an affirmative person, a
      mediator, a guarantor, a fixer and as an accessible presence. KEY CONCLUSION: for
      these women, the doula fulfilled important needs. The roles of the midwife and
      the doula differ, yet some of the evolved doula supportive functions are also
      essential in the midwife's care. When a birthing woman has chosen a doula, the
      challenge for the midwife is to support her in collaboration with the doula and
      the partner if present. More research is needed in order to determine whether the
      presence of a doula for the midwife is an asset or a hindrance, and to find the
      essential prerequisites for midwife-doula collaboration to be possible.

PMID- 16603284
TI  - Midwifery students' enrolment reasons and evaluations of the first Bachelor of
      Midwifery programme in Jordan.
AB  - OBJECTIVE: to explore reasons for enrolment in the first bachelor of midwifery
      programme in Jordan, and to describe midwifery students' evaluations of the
      programme. DESIGN: a cross-sectional survey design. SETTING: The Faculty of
      Nursing at Jordan University of Science and Technology, Irbid, Jordan.
      PARTICIPANTS: 16 diploma-prepared midwifery students enrolled in the 2-year
      bachelor-completion programme. MEASUREMENTS AND FINDINGS: an open-ended question
      explored students' reasons for enrolling in the midwifery programme. For
      programme evaluation, a 13-item Midwifery Programme Evaluation Questionnaire
      (MPEQ) was developed and used. Total score ranged from 39-61, with a mean of 51.2
      (SD=6.7). CONCLUSION: midwifery students reported five reasons for enrolling in
      the midwifery programme, which was favourably evaluated. IMPLICATIONS FOR
      PRACTICE: encouragement and sustainability of student enrolment in the JUST
      Bachelor of Midwifery programme are recommended to improve midwifery education
      and enhance midwifery as a profession.

PMID- 16603285
TI  - The effect of patella resurfacing in total knee arthroplasty on functional range
      of movement measured by flexible electrogoniometry.
AB  - BACKGROUND: The need for patella resurfacing remains an area of considerable
      controversy in total knee replacement surgery. There would appear to be no
      reported evidence on the effect of patella resurfacing on knee function, as
      measured by functional range of movement used in a series of tasks, in patients
      undergoing knee replacement. The object of this study was to measure knee joint
      motion during functional activities both prior to and following total knee
      replacement in a randomised group of patients with and without patella
      resurfacing and to compare these patient groups with a group of normal age
      matched subjects. METHODS: The study design was a double blinded, randomised,
      prospective, controlled trial. The knee joint functional ranges of movement of a
      group of patients (n=50, mean age=70 years) with knee osteoarthritis were
      investigated prior to and following total knee arthroplasty (4 months and 18-24
      months) along with a group of normal subjects (n=20, mean age=67). Patients were
      randomly allocated into two groups, those who received patella resurfacing (n=25)
      and those who did not (n=25). Flexible electrogoniometry was used to measure the
      flexion-extension angle of the knees with respect to time in eleven functional
      activities. FINDINGS: No statistically significant differences (alpha level 0.05)
      in joint excursion of the affected knee were found between patients who received
      patella resurfacing and those who did not. INTERPRETATION: Routine patella
      resurfacing in a typical knee arthroplasty population does not result in an
      increase in the functional range of movement used after knee replacement.

PMID- 16603286
TI  - Suprascapular nerve block disrupts the normal pattern of scapular kinematics.
AB  - BACKGROUND: Patients with full thickness rotator cuff tears typically demonstrate
      an increase in scapular motion, both in the clinic and under controlled
      laboratory conditions. To better understand the mechanisms behind this pattern of
      motion, we propose a suprascapular nerve block as an appropriate model of
      dysfunction of the supraspinatus and infraspinatus, which are the two tendons
      most commonly affected in cuff tear patients. METHODS: Healthy subjects underwent
      testing for 3D scapular kinematics with a Polhemus magnetic tracking device and
      isometric force measurements during external rotation. A suprascapular nerve
      block was then performed with the injection of lidocaine into the suprascapular
      notch of each subject. Scapular kinematics and isometric force measurements were
      repeated after confirmation of the block. FINDINGS: The nerve block resulted in
      no significant changes in clavicular rotations and scapular posterior tilting.
      However, there was a significant increase in scapular external rotation and
      upward rotation. While kinematic changes returned to baseline within 25 min of
      the block, force measurements did not return to baseline until 75 min post-block.
      Interpretation. The results of this study, especially those for upward rotation,
      are in general agreement with what has been found for patients with rotator cuff
      tears. While the supraspinatus and infraspinatus do not directly control the
      movement of the scapula, they appear to result in a compensatory change in
      scapular motion. Although more work needs to be done, it appears that abnormal
      scapular motion patterns observed in patients with cuff tears may therefore be
      compensatory in nature.

PMID- 16603287
TI  - Influence of a custom foot orthotic intervention on lower extremity dynamics in
      healthy runners.
AB  - OBJECTIVE: To investigate the influence of a custom foot orthotic intervention on
      the lower extremity dynamics in healthy runners. DESIGN: Three-dimensional
      kinematics and kinetics were collected on 15 female runners (>15 miles per week)
      while each performed the over-ground running trials in either a shoe only or a
      shoe+custom foot orthotic condition. Kinematic and kinetic variables were
      analyzed using Paired Sample t-tests. BACKGROUND: Custom foot orthotics are
      frequently prescribed treatment modality for the management of overuse running
      injuries. Although it is generally accepted that a custom foot orthotic
      intervention produces positive clinical outcomes, it remains unclear what
      influence this therapeutic modality has on the dynamics of the lower extremity.
      METHODS: Each subject performed five acceptable over-ground running trials (3.6 m
      s(-1) +/-5%) with and without the custom foot orthotic intervention in a running
      shoe. Selected maximum ankle and knee joint angles and moments were measured
      during the stance phase. RESULTS: While wearing the custom foot orthotic,
      subjects exhibited significantly decreased maximum values in rearfoot eversion
      angle, rearfoot eversion velocity and internal ankle inversion moment.
      CONCLUSIONS: In this sample of healthy female runners, the custom foot orthotic
      intervention led to significant decreases in maximum values for ankle dynamics in
      the frontal plane and in the sagittal plane of the knee joint. Relevance It
      remains unclear how a custom foot orthotic intervention influences lower
      extremity dynamics to produce positive clinical outcomes. Furthering our
      understanding of the dynamic influence will not only inform improved prescription
      and manufacturing practices but may provide insight into the mechanisms that
      cause overuse injuries.

PMID- 16603288
TI  - Polychlorinated biphenyls and polybrominated diphenyl ethers in the North
      American atmosphere.
AB  - To assess the spatial concentration variability of polychlorinated biphenyls
      (PCBs) and polybrominated diphenyl ethers (PBDEs) in the atmosphere on a large
      continental scale, their annually integrated air concentrations were determined
      in 2000/2001 using XAD-based passive air samplers (PAS). The network included 40
      stations in Canada, the United States, Mexico, Belize and Costa Rica, and covered
      72 degrees of latitude and longitude. Total concentrations of PCB and PBDE
      congeners ranged from below the detection limit to 130 ng PAS-1 and 24 ng PAS-1,
      respectively. PCBs displayed a large variation between urban, rural and remote
      sites, whereas PBDEs did not follow such a pattern. Open burning of "Penta"
      containing waste may have contributed to the PBDEs detected in the air samples
      from rural and remote areas. Air from the Canadian Arctic had a relatively higher
      percentage of lighter PCB congeners than air sampled in the tropical region,
      which is interpreted as evidence for global fractionation.

PMID- 16603289
TI  - Relationships between the abnormalities of the male reproductive organs and the
      accumulation of phenol compounds in the striped field mouse, Apodemus agrarius,
      inhabiting Korea.
AB  - The relationships between the abnormalities of the male reproductive organs in
      striped field mice and the accumulation of endocrine-disrupting chemicals were
      assessed. Most mice collected at three areas were contaminated with phenol or
      organotin compounds. Fourteen to 42% of the mice at each area had abnormally
      shrunken reproductive organs, and some of them were contaminated with high levels
      of phenol compounds. Moreover, all the shrunken reproductive organs were damaged
      in the histological structure. The damage was observed also from several mice
      accumulating a high level of phenol compounds even though they had normally
      developed reproductive organs, although no damage was found in the mice
      accumulating a high level of organotin compounds. Collectively, the abnormalities
      of the reproductive organs in the mice seemed to be related to the accumulation
      of phenol compounds rather than of organotin compounds.

PMID- 16603290
TI  - Evaluation of a biomarker of Cd(II) exposure on Limnoperna fortunei.
AB  - The use of organisms to monitor contamination allows the access to information
      that cannot be acquired by chemical methods. Limnoperna fortunei, mussel
      frequently found in Rio de la Plata estuary, fulfils the requirements to be used
      as a biomonitoring organism. In this work we report that a polypeptide of 22 kDa
      of molecular weight (LF22) is induced when L. fortunei is exposed to Cd (II),
      Cu(II) and Hg(II) sublethal levels. To characterize LF22, mussels were sampled
      from a non-polluted region and whole soft tissue was homogenized, with and
      without previous exposure to 100 microg/L of Cd(II). The cytosolic proteins were
      evaluated by mono and bidimensional SDS-PAGE, and size exclusion chromatography.
      All the methods showed that LF22 triples its concentration in presence of Cd(II).
      Purification of LF22 was achieved by fractioned precipitation, salting-out, ionic
      exchange and size exclusion chromatography. We conclude that LF22 is a useful
      biomarker of heavy metal exposure.

PMID- 16603291
TI  - Interpreting time trends and biomagnification of PCBs in the Baltic region using
      the equilibrium lipid partitioning approach.
AB  - Multi-year monitoring data for PCBs in abiotic media and biota collected from the
      Baltic region were compiled into a database and analyzed using the equilibrium
      lipid partitioning (ELP) approach to study temporal trends as well as to
      investigate food web biomagnification. Statistically significant reductions in
      ELP concentrations between 1987 and 2001 were observed in guillemots, air, and
      some fish species and a general, but not always statistically significant decline
      in concentrations was observed throughout the Baltic ecosystem. Estimated
      clearance half-lives ranged from 2.7-10.7 years. The database contained
      concentrations for a range of different Baltic species, which comprise a well
      known Baltic food web. It was possible to derive the trophic position of the
      species in this food web and relate them to ELP concentrations. A significant
      positive correlation between ELP concentrations and trophic position was
      obtained. Estimated food web magnification factors ranged between 1.9 and 5.1 for
      selected congeners.

PMID- 16603292
TI  - A test of sequential extractions for determining metal speciation in sewage
      sludge-amended soils.
AB  - Sequential extraction procedures are widely used to estimate the quantity of
      trace metals bound to different solid fractions in contaminated soils. However,
      reliability of speciation of trace metals by these procedures remains largely
      unexamined. In the present study, the selectivity of each extraction step was
      tested by observing the effect of reversing the extraction order in the
      procedure. Two different sequential extraction methods and their reversed modes
      were used for metal fractionation in sewage sludge-amended soils. Significantly
      increased amounts of extractable metals (Cd, Cu, Pb and Zn) were evident in the
      sludge-amended soils compared to control soil by all extraction schemes; however,
      the amounts of metals extracted by each step were strongly dependent on the order
      of extraction, the type of reagents and the nature of the individual metals.
      Caution is advised in deducing the forms of soil metals from sequential
      extraction results from metal-contaminated soils.

PMID- 16603293
TI  - Distribution and sources of polycyclic aromatic hydrocarbons in the middle and
      lower reaches of the Yellow River, China.
AB  - In this study, concentrations, distribution between different phases, transition
      along the Middle and Lower reaches of the Yellow River and possible sources of
      PAHs were assessed. Results demonstrated that the relative proportions of 15 PAHs
      in all stations of the main River were similar, with concentrations of
      benzo[a]pyrene all above drinking water standards in most of the stations
      sampled. PAHs concentrations in tributaries were higher than those in the
      corresponding sites in the main River. PAHs concentrations of suspended particles
      were mainly correlated with contents of total organic carbon. However, PAHs
      concentrations in sediments were mainly correlated to the volume of particles
      with size smaller than 0.01 mm. The distribution of PAHs in all media sampled
      indicated that sediments could act as a sink/source for PAHs in different
      sections and source analysis revealed that PAHs mainly originated from coal
      burning, although in some tributaries PAH inputs could come from combustion of
      petroleum.

PMID- 16603294
TI  - Evaluating fugacity models for trace components in landfill gas.
AB  - A fugacity approach was evaluated to reconcile loadings of vinyl chloride
      (chloroethene), benzene, 1,3-butadiene and trichloroethylene in waste with
      concentrations observed in landfill gas monitoring studies. An evaluative
      environment derived from fictitious but realistic properties such as volume,
      composition, and temperature, constructed with data from the Brogborough landfill
      (UK) test cells was used to test a fugacity approach to generating the source
      term for use in landfill gas risk assessment models (e.g. GasSim). SOILVE, a
      dynamic Level II model adapted here for landfills, showed greatest utility for
      benzene and 1,3-butadiene, modelled under anaerobic conditions over a 10 year
      simulation. Modelled concentrations of these components (95,300 microg m(-3); 43
      microg m(-3)) fell within measured ranges observed in gas from landfills (24,300
      180,000 microg m(-3); 20-70 microg m(-3)). This study highlights the need (i) for
      representative and time-referenced biotransformation data; (ii) to evaluate the
      partitioning characteristics of organic matter within waste systems and (iii) for
      a better understanding of the role that gas extraction rate (flux) plays in
      producing trace component concentrations in landfill gas.

PMID- 16603295
TI  - Influence of solution acidity and CaCl2 concentration on the removal of heavy
      metals from metal-contaminated rice soils.
AB  - Soil washing is considered a useful technique for remediating metal-contaminated
      soils. This study examined the release edges of Cd, Zn, Ni, Cr, Cu or Pb in two
      contaminated rice soils from central Taiwan. The concentrations exceeding the
      trigger levels established by the regulatory agency of Taiwan were Cu, Zn, Ni and
      Cr for the Ho-Mei soil and Pb for the Nan-Tou soil. Successive extractions with
      HCl ranging from 0 to 0.2 M showed increased release of the heavy metals with
      declining pH, and the threshold pH value below which a sharp increase in the
      releases of the heavy metals was highest for Cd, Zn, and Ni (pH 4.6 to 4.9),
      intermediate for Pb and Cu (3.1 to 3.8) and lowest for Fe (2.1), Al (2.2) and Cr
      (1.7) for the soils. The low response slope of Ni and Cr particularly for the
      rice soils make soil washing with the acid up to the highest concentration used
      ineffective to reduce their concentrations to below trigger levels. Although soil
      washing with 0.1 M HCl was moderately effective in reducing Cu, Pb, Zn and Cd,
      which brought pH of the soils to 1.1+/-0.1 (S.D.), the concurrent release of
      large quantities of Fe and Al make this remediation technique undesirable for the
      rice soils containing high clay. Successive washings with 0.01 M HCl could be
      considered an alternative as the dissolution of Fe and Al was minimal, and
      between 46 to 64% of Cd, Zn, and Cu for the Ho-Mei soil and 45% of Pb in the Na
      Tou soil were extracted after four successive extractions with this dilute acid
      solution. The efficacy of Cd extraction improved if CaCl2 was added to the acid
      solution. The correlation analysis revealed that Cr extracted was highly
      correlated (P < 0.001) with Fe extracted, whereas the Cu, Ni, Zn, Cd or Pb
      extracted was better correlated (P < 0.001) with Al than with Fe extracted. It is
      possible that the past seasonal soil flooding and drainage in the soils for rice
      production was conducive to incorporating Cr within the structure of Fe oxide,
      thereby making them extremely insoluble even in 0.2 M HCl solution. The formation
      of solid solution of Ni with Al oxide was also possible, making it far less
      extractable than Cd, Zn, Cu, or Pb with the acid concentrations used.

PMID- 16603296
TI  - Photodegradation of bisphenol A in simulated lake water containing algae, humic
      acid and ferric ions.
AB  - The photodegradation of bisphenol A (BPA), a suspected endocrine disruptor (ED),
      in simulated lake water containing algae, humic acid and Fe3+ ions was
      investigated. Algae, humic acid and Fe3+ ions enhanced the photodegradation of
      BPA. Photodegradation efficiency of BPA was 36% after 4h irradiation in the
      presence of 6.5 x 10(9) cells L(-1) raw Chlorella vulgaris, 4 mg L(-1) humic acid
      and 20 micromol L(-1) Fe3+. The photodegradation efficiency of BPA was higher in
      the presence of algae treated with ultrasonic than that without ultrasonic. The
      photodegradation efficiency of BPA in the water only containing algae treated
      with ultrasonic was 37% after 4h irradiation. The algae treated with heating can
      also enhance the photodegradation of BPA. This work helps environmental
      scientists to understand the photochemical behavior of BPA in lake water.

PMID- 16603297
TI  - Providers' constructions of the role of women in cervical cancer screening in
      Bulgaria and Romania.
AB  - The social and institutional context of health-care reform in Eastern Europe has
      important implications for cervical cancer screening and prevention. The
      incidence and mortality from cervical cancer in Bulgaria and Romania have risen,
      which is in sharp contrast to the steady decline in most other countries in
      Europe during the last 2 decades. To analyze these dynamics we conducted a multi
      component study of health systems and psychosocial aspects of cervical cancer
      screening in Bulgaria and Romania. Following the disappearance of organized
      preventive programs, the initiative for cervical cancer screening has shifted to
      providers and clients and depends on the way they perceive their responsibility
      and interpret their own and each other's roles in prevention. We focus on how
      providers construct women and their role in prevention of cervical cancer through
      their accounts. The analysis identified several discourses and themes in
      providers' constructions of women's responsibility for prevention of disease.
      These include responsible women as 'intelligent' and 'cultured'; non-attenders as
      'irresponsible' and 'negligent'; women as needing monitoring and sanctioning; and
      women as 'victims' of health-care reform. We discuss the implications for health
      care reform and health promotion.

PMID- 16603298
TI  - The pros and cons of social relations: an analysis of adolescents' health
      complaints.
AB  - This paper examines the association between social relations and psychological
      and psychosomatic health complaints, among adolescents in Sweden. We focused on
      relationships with parents, as well as relationships with peers in school and in
      leisure time. Both the structure and the content of relations were analysed. For
      the latter, we looked at supportive as well as strained relations. The data was
      the pooled child supplements of the Swedish welfare surveys conducted in 2000
      2003. This constitutes a nationally representative, cross-sectional sample of 10
      18-year-olds (n = 5137), where information was collected from both adolescents
      and their parents. Results showed that young people's social relations with
      parents and peers clearly covaried with their health complaints. With regard to
      family relations and psychological complaints, the association was more
      pronounced for relational content than for relational structure. For instance,
      whether relations with parents were strained or not seemed more relevant than
      family structure and parental working hours. Moreover, strained relations were
      more strongly associated with health complaints, especially psychosomatic
      complaints, than were supportive relations. This applied to relationships with
      parents as well as with peers in school.

PMID- 16603299
TI  - Predicting intended use of voluntary HIV counselling and testing services among
      Tanzanian teachers using the theory of planned behaviour.
AB  - The theory of planned behaviour (TPB) provides a conceptual model for
      understanding individual cognitions that influence behavioural intentions and
      enactment of the actual behaviours. This study examined the applicability of the
      TPB and the additional predictive role of perceived risk in predicting intended
      use of voluntary HIV counselling and testing (VCT) services. We conducted a cross
      sectional questionnaire survey among 918 primary school teachers in the Mwanza
      region, Tanzania between September 2003 and November 2003. Analysis was based on
      737 teachers (mean age 38.9) who had never tested for HIV. Results of the
      hierarchical regression analysis indicate that perceived behavioural control and
      attitude toward using VCT services were significant predictors of intention to
      use VCT services in the TPB model. Perceived behavioural control added 12% of
      variance to intention over and above attitudes and subjective norms, while
      perceived risk added 3% of variance. Socio-economic status did not moderate the
      predictive value of the TPB components. The present study demonstrates that the
      TPB is a useful conceptual framework for predicting intended use of HIV
      counselling and testing services among Tanzanian teachers. A theory-based VCT
      intervention programme among Tanzanian teachers should mainly focus on reducing
      social and psychological barriers related to the use of VCT services.

PMID- 16603300
TI  - Age differences in fluid intelligence: contributions of general slowing and
      frontal decline.
AB  - The current study examined the contributions of general slowing and frontal
      decline to age differences in fluid intelligence. Participants aged 20-89 years
      completed Block Design, Matrix Reasoning, simple reaction time, choice reaction
      time, Wisconsin Card Sorting, and Tower of London tasks. Age-related declines in
      fluid intelligence, speed of processing, and frontal function were observed.
      Hierarchical regression analyses showed that the processing speed and frontal
      function measures accounted for significant variance in fluid intelligence
      performance, but there was also a residual effect of age after controlling for
      each variable individually as well as both variables. An additional analysis
      showed that the variance in fluid intelligence that was attributable to
      processing speed was not fully shared with the variance attributable to frontal
      function. These findings suggest that the age-related decline in fluid
      intelligence is due to general slowing and frontal decline, as well as other
      unidentified factors.

PMID- 16603301
TI  - Efficacy of milnacipran on the depressive state in patients with Alzheimer's
      disease.
AB  - An open-labeled study was conducted to examine the efficacy of selective
      serotonin and noradrenaline reuptake inhibitor (SNRI), milnacipran in treating
      depression in Alzheimer's disease (AD) patients. Eleven patients with AD showing
      major depressive symptoms were examined. Ten of 11 patients demonstrated an over
      50% decrease in their HAM-D scores from the baseline, and 8 of 11 patients
      reached remission (HAM-D score<==7) within 12 weeks of the start of milnacipran
      treatment, and their GAF score was also remarkably improved. Although in 11
      patients, two patients showed a mild hypomanic state and one patient showed
      daytime somnolence, these problems were quickly solved after a decrease in the
      daily dose or discontinuation of milnacipran. In addition, the treatment had no
      negative effects on cognitive function of the patients. Our study results suggest
      that milnacipran is a promising medicine for depressive state in AD patients.

PMID- 16603302
TI  - Support for an association between mismatch negativity and social functioning in
      schizophrenia.

PMID- 16603303
TI  - [Abdominoplasty: towards a two procedures surgery? Retrospective study of
      postoperative complications about 100 cases].
AB  - Abdominoplasty has become in France a frequent, appearing to be technically easy
      but nevertheless source of potentially serious complications clearly
      deteriorating the aesthetic results and the satisfaction rate of the patients. By
      studying the results of a hundred abdominoplasties performed between 2001 and
      2004, we could count the incidence of the various complications by seeking their
      possible factors of risk (tobacco or ponderal overload). In spite of the use of a
      lymphatic preserving technique, the percentage of seroma reaches 12%. The high
      complications rate or the number of insufficient results explains a rate of
      surgical reoperation of 31%. Abdominoplasty passed from the statute of repairing
      surgery to that of aesthetic surgery. The level standard in terms of result
      became equivalent to the other purely aesthetic interventions. Obtaining an
      optimal result thus requires often two operational stages, data element that it
      henceforth seems essential to us to provide to the patients.

PMID- 16603304
TI  - Absence of in vivo genotoxic potential and tumor initiation activity of kojic
      acid in the rat thyroid.
AB  - To clarify the in vivo genotoxic potential of kojic acid (KA), formation of DNA
      adducts and 8-hydroxy-deoxyguanosine (8-OHdG) in the thyroids of male rats
      subjected to dietary administration of 2% KA for 2 weeks were assessed by 32P
      postlabeling analysis and with a high-performance liquid chromatography system
      coupled to an electrochemical detector (ECD), respectively. In addition, to
      investigate possible tumor initiation activity, male F344 rats were given diet
      containing 0, 0.02, 0.2 or 2% kojic acid for 8 weeks followed by administration
      of 0.1% sulfadimethoxine (SDM), a thyroid tumor promoter, in the drinking water
      for 23 weeks with a subsequent 13-week recovery period (two-stage thyroid
      tumorigenesis model). Rats given four times by s.c. injection of N-bis(2
      hydroxypropyl)nitrosamine (DHPN; 700 mg/kg bw) during the initiation period
      followed by administration of 0.1% SDM and rats given diet containing 2% KA for
      the initial 8 weeks or for the entire 31 weeks of the experiment, or basal diet
      alone were provided as controls. DNA adducts were not formed, and the 8-OHdG
      level was not increased in the thyroids of rats given 2% KA for 2 weeks. In the
      two-stage thyroid tumorigenesis model, neither adenomas nor carcinomas were
      induced in the groups given 0, 0.02, 0.2 or 2% KA followed by 0.1% SDM
      administration, and incidences and multiplicities of focal follicular cell
      hyperplasias did not demonstrate any significant intergroup differences at the
      end of administration and recovery periods. In contrast, incidences and
      multiplicities of focal follicular cell hyperplasias, adenomas and carcinomas
      were all significantly increased in the DHPN + 0.1% SDM group. Although the
      incidences and multiplicities of focal follicular cell hyperplasias in the group
      given 2% KA for 31 weeks were greater than those in the 2% KA + 0.1% SDM group
      and an adenoma was observed in a rat at the end of the recovery period, no
      development of carcinomas was evident at either time point. No thyroid
      proliferative lesions were induced in the group given 2% KA for the initial 8
      weeks only. The results of the present studies indicate that KA has neither in
      vivo genotoxic potential nor tumor initiation activity in the thyroid, and
      strongly suggest that the earlier observed thyroid tumorigenic activity of KA is
      attributable to a non-genotoxic mechanism.

PMID- 16603305
TI  - Association between oral malodor and measurements obtained using a new sulfide
      monitor.
AB  - OBJECTIVE: The purpose of this study was to evaluate the ability of a new
      volatile sulfur compounds (VSCs) monitor to assess oral malodor in subjects and
      compare its performance with those of organoleptic testing and gas
      chromatography. METHODS: The mouth air of 260 patients was measured by three
      methods: VSCs monitor (Breathtron), organoleptic test by two judges and gas
      chromatography (GC). Mcnemar test and Pearson correlation were used to analyze
      the data among these methods. RESULTS: The log values of VSCs measured by a
      sulfide monitor were significantly correlated with the organoleptic ratings, and
      also with log values of H(2)S, CH(3)SH, and (CH(3))(2)S determined by GC
      (P<0.01). Using the results of organoleptic and GC to classify subjects into
      normal and malodor groups, the sulfide monitor's sensitivity was shown to be more
      than 79% and the specificity was 61-73%. CONCLUSIONS: This sulfide monitor could
      be used for oral malodor measurement, moreover, according to its portability, it
      could be conveniently used for clinical setting and field surveys.

PMID- 16603307
TI  - Reflections on the origins of microcalorimetry of biopolymers.

PMID- 16603306
TI  - Thermodynamics of the purine nucleotide cycle.
AB  - Since the standard Gibbs energies of formation are known for all the species in
      the purine nucleotide cycle at 298.15 K, the functions of pH and ionic strength
      that yield the standard transformed Gibbs energies of formation of the ten
      reactants can be calculated. This makes it possible to calculate the standard
      transformed Gibbs energies of reaction, apparent equilibrium constants, and
      changes in the binding of hydrogen ions for the three reactions at desired pHs
      and ionic strengths. These calculations are also made for the net reaction and a
      reaction that is related to it. The equilibrium concentrations for the cycle are
      calculated when all the reactants are initially present or only some are present
      initially. Since the concentrations of GTP, GDP, and P(i) may be in steady
      states, the equilibrium concentrations are also calculated for the system at
      specified steady-state concentrations.

PMID- 16603308
TI  - Evidence for a synergistic salt-protein interaction -- complex patterns of
      activation vs. inhibition of nitrogenase by salt.
AB  - The molybdenum nitrogenase enzyme system, comprised of the MoFe protein and the
      Fe protein, catalyzes the reduction of atmospheric N(2) to NH(3). Interactions
      between these two proteins and between Fe protein and nucleotides (MgADP and
      MgATP) are crucial to catalysis. It is well established that salts are inhibitors
      of nitrogenase catalysis that target these interactions. However, the
      implications of salt effects are often overlooked. We have reexamined salt
      effects in light of a comprehensive framework for nitrogenase interactions to
      offer an in-depth analysis of the sources of salt inhibition and underlying
      apparent cooperativity. More importantly, we have identified patterns of salt
      activation of nitrogenase that correspond to at least two mechanisms. One of
      these mechanisms is that charge screening of MoFe protein-Fe protein interactions
      in the nitrogenase complex accelerates the rate of nitrogenase complex
      dissociation, which is the rate-limiting step of catalysis. This kind of salt
      activation operates under conditions of high catalytic activity and low salt
      concentrations that may resemble those found in vivo. While simple kinetic
      arguments are strong evidence for this kind of salt activation, further
      confirmation was sought by demonstrating that tight complexes that have
      previously displayed little or no activity due to the inability of Fe protein to
      dissociate from the complex are activated by the presence of salt. This occurs
      for the combination Azotobacter vinelandii MoFe protein with: (a) the L127Delta
      Fe protein; and (b) Clostridium pasteurianum Fe protein. The curvature of
      activation vs. salt implies a synergistic salt-protein interaction.

PMID- 16603309
TI  - Dielectric properties of E. coli cell as simulated by the three-shell spheroidal
      model.
AB  - Dielectric properties of E. coli cell have been re-studied by means of the three
      shell spheroidal model, where the three shells correspond to the outer membrane,
      the periplasmic space and the inner membrane, respectively. With the model, a
      curve-fitting procedure has been developed to analyze the dielectric spectra.
      Although E. coli cell has been studied before, its special morphological
      structure was taken into account more comprehensively than any previous model in
      the present work. Dielectric properties of various cell components have been
      estimated from the observed dielectric spectra, especially the permittivity of
      the outer membrane, which was evaluated quantitatively for the first time. The
      values of epsilon(om) were 12 for kappa(om) of 0 to 10(-4) S/m and 34 for
      kappa(om) of 10(-3) S/m. The specific capacitance of the inner membrane was 0.6
      0.70 microF/cm(2). The relative permittivity and the conductivity of the
      cytoplasm were about 100 and 0.22 S/m, respectively, and the conductivity of the
      periplasmic space was 2.2-3.2 S/m.

PMID- 16603310
TI  - Decoloration of aqueous Brilliant Green by using glow discharge electrolysis.
AB  - This paper described a plasma degradation of Brilliant Green (BG) by glow
      discharge electrolysis. Various influencing factors such as the voltage, the
      distance between cathode and anode were examined. Ultraviolet (UV) absorption
      spectra, gas chromatogram-mass spectrum (GC-MS), and chemical oxygen demand (COD)
      were used to monitor the degradation process and to identify the major oxidation
      intermediates. It was confirmed that benzoic acid, 1,2,3,4,5,6-cyclohexanehexaol,
      and carboxylic acids (e.g., oxalic acid, succinic acid and hydroxyacetic acid)
      were produced in the degradation process. The results showed that BG rapidly
      underwent degradation and eventually mineralized into CO(2) and H(2)O.

PMID- 16603311
TI  - Use of agricultural waste sugar beet pulp for the removal of Gemazol turquoise
      blue-G reactive dye from aqueous solution.
AB  - The potential use of dried sugar beet pulp, an agricultural solid waste by
      product, as an biosorbent for Gemazol turquoise blue-G, a copper-pthalocyanine
      reactive dye commonly used in dyeing of cotton, was investigated in the present
      study. Batch adsorption studies were carried out to examine the influence of
      various parameters such as initial pH, temperature and initial dye concentration.
      The results indicated that adsorption was strongly pH-dependent and slightly
      temperature-dependent. At 800 mg l(-1) initial Gemazol turquoise blue-G
      concentration, dried sugar beet pulp exhibited the highest Gemazol turquoise blue
      G uptake capacity of 234.8 mg g(-1) at 25 degrees C and at an initial pH value of
      2.0. The Freundlich, Langmuir, Redlich-Peterson and Langmuir-Freundlich, the two
      and three parameters adsorption models were used for the mathematical description
      of the biosorption equilibrium and isotherm constants were evaluated depending on
      temperature. Both the Langmuir and Redlich-Peterson models were applicable for
      describing the dye biosorption by dried sugar beet pulp in the concentration (100
      800 mg l(-1)) and temperature (25-45 degrees C) ranges studied. Simple mass
      transfer and kinetic models were applied to the experimental data to examine the
      mechanisms of biosorption and potential rate controlling steps such as external
      mass transfer, intraparticle diffusion and biosorption process. The sorption
      process was found to be controlled by both surface and pore diffusion with
      surface diffusion at the earlier stages followed by pore diffusion at the later
      stages. Pseudo first-order, pseudo second-order and saturation type kinetic
      models described the biosorption kinetics accurately at all concentrations and
      temperatures studied. The thermodynamic analysis indicated that the sorption
      process was exothermic and the biosorption of dye on dried sugar beet pulp might
      be physical in nature.

PMID- 16603312
TI  - Removal of copper(II) and lead(II) from aqueous solution by manganese oxide
      coated sand I. Characterization and kinetic study.
AB  - The preparation, characterization, and sorption properties for Cu(II) and Pb(II)
      of manganese oxide coated sand (MOCS) were investigated. A scanning electron
      microscope (SEM), X-ray diffraction spectrum (XRD) and BET analyses were used to
      observe the surface properties of the coated layer. An energy dispersive analysis
      of X-ray (EDAX) and X-ray photoelectron spectroscopy (XPS) were used for
      characterizing metal adsorption sites on the surface of MOCS. The quantity of
      manganese on MOCS was determined by means of acid digestion analysis. The
      adsorption experiments were carried out as a function of solution pH, adsorbent
      dose, ionic strength, contact time and temperature. Binding of Cu(II) and Pb(II)
      ions with MOCS was highly pH dependent with an increase in the extent of
      adsorption with the pH of the media investigated. After the Cu(II) and Pb(II)
      adsorption by MOCS, the pH in solution was decreased. Cu(II) and Pb(II) uptake
      were found to increase with the temperature. Further, the removal efficiency of
      Cu(II) and Pb(II) increased with increasing adsorbent dose and decreased with
      ionic strength. The pseudo-first-order kinetic model, pseudo-second-order kinetic
      model, intraparticle diffusion model and Elovich equation model were used to
      describe the kinetic data and the data constants were evaluated. The pseudo
      second-order model was the best choice among all the kinetic models to describe
      the adsorption behavior of Cu(II) and Pb(II) onto MOCS, suggesting that the
      adsorption mechanism might be a chemisorption process. The activation energy of
      adsorption (E(a)) was determined as Cu(II) 4.98 kJ mol(-1) and Pb(II) 2.10 kJ
      mol(-1), respectively. The low value of E(a) shows that Cu(II) and Pb(II)
      adsorption process by MOCS may involve a non-activated chemical adsorption and a
      physical sorption.

PMID- 16603313
TI  - Reduction of disinfection by-products precursors by nanofiltration process.
AB  - This research is dedicated to determine the rejection ratios of disinfection by
      products (DBPs) precursors including resorcinol, phloroglucinol, 3-hydroxybenzoic
      acid, and tannic acid solution in the presence of calcium by nanofiltration with
      NF70 membrane. The rejections of these model compounds also were studied at
      various compositions of a feed solution by changing pH and concentrations of
      model compounds. It was found that the model compound rejection and membrane
      permeability increase with pH due to the conformational transformation of
      ionizable molecules and electric interaction between the model compounds and NF70
      membrane. The interactions of model compounds with calcium have no significant
      effect on model compounds retentions. Because of the complexation of calcium with
      model compounds, calcium rejection rises with the presence of model compounds and
      with an increase of pH.

PMID- 16603314
TI  - Inhibition of cGMP-dependent protein kinase by the regulatory subunit of
      photoreceptor cGMP phosphodiesterase.
AB  - cGMP-dependent protein kinases (PKGs) mediate many cellular processes including
      neuronal signaling. The functional significance of PKG I in neurons is emphasized
      by recent findings that indicate its broad distribution in the brain and eye. In
      the photosensitive neurons (photoreceptors), the inhibitory gamma subunit
      (Pgamma) of the central effector cGMP phosphodiesterase (PDE6) modulates visual
      signaling through a cooperative binding together with cGMP to the regulatory
      domains of the PDE6 catalytic subunits. Here, we report that PKG Ialpha is
      inhibited by Pgamma. Kinase activity assays showed that the maximum inhibition of
      PKG by Pgamma was similar to that by a specific PKG inhibitor. The N-terminal
      half (Pgamma1-61) containing a polycationic region was found to be a more potent
      PKG inhibitor as compared to the full-length molecule, whereas the C-terminus
      (Pgamma62-87) did not inhibit PKG activity. Pgamma itself was not found to be a
      phosphorylation substrate of PKG. This finding may provide important insights
      into the modulations in neurons and other cells.

PMID- 16603315
TI  - Sequence variants of ACE, AGT, AT1R, and PAI-1 as genetic risk factors for
      vascular dementia.
AB  - Sequence variants of angiotensin converting enzyme (ACE) insertion/deletion
      (I/D), angiotensinogen (AGT) T235M, angiotensin II type 1 receptor (AT1R) A1166C,
      and plasminogen activator inhibitor-1 (PAI-1) 4G/5G were analyzed to see their
      genetic associations with vascular dementia as its candidate genetic risk factors
      involving renin-angiotensin and fibrin systems. While the ACE I/D, AT1R A1166C,
      and PAI-1 4G/5G did not contribute to the genetic susceptibility to vascular
      dementia (P>0.05), a significant association with vascular dementia was shown in
      the T235M polymorphism of AGT. The frequency of the M allele in patients was
      higher than in controls with the odds ratio (OR) estimate of 1.51 (P<0.05). In a
      dominant model, the TM+MM genotypes increased the risk of vascular dementia
      compared to the TT genotype (OR=2.01; P<0.001). The current results suggested
      that AGT T235M polymorphism might be a risk factor of vascular dementia.

PMID- 16603316
TI  - Use-dependent behavioral and neurochemical asymmetry in MPTP mice.
AB  - Early in Parkinson's disease (PD) physical activity becomes difficult resulting
      in a more sedentary lifestyle. Clinical and experimental studies have found that
      increased activity following striatal dopamine loss leads to increased motor
      function. Decreased physical activity early in PD along with findings that
      increased physical activity results in functional improvement suggested to us
      that decreased physical activity during the period of nigrostriatal degeneration
      may not only be a symptom of the injury, but may also act to potentiate the
      degeneration. Using the bilateral MPTP mouse model of PD, we restricted use of
      one forelimb for the first 7 days post-injection. This transient behavioral
      manipulation during the period of dopamine degeneration resulted in a long
      lasting deficit of the restricted forelimb. This was manifested as sustained
      asymmetrical use of the forelimbs during wall exploration, as well as a
      neurochemical imbalance between striatal hemispheres measured by immunoreactivity
      of the dopamine terminal markers, DAT, VMAT2 and TH. These results show a
      significant interaction between behavior and neurochemistry and suggest that a
      reduction in activity level may further exacerbate degeneration.

PMID- 16603317
TI  - Antibiotics plus granulocyte colony-stimulating factor reduces febrile
      neutropenia in the first cycle of chemotherapy in people with small-cell lung
      cancer.

PMID- 16603318
TI  - Immunohistochemical localization of cannabinoid type 1 and vanilloid transient
      receptor potential vanilloid type 1 receptors in the mouse brain.
AB  - Cannabinoid type 1 receptors and transient receptor potential vanilloid type 1
      channels have been proposed to act as metabotropic and ionotropic receptors,
      respectively, for two classes of endogenous polyunsaturated fatty acid amides,
      the acylethanolamides and the acyldopamides. Furthermore, we and others have
      shown that functional crosstalk occurs between these two receptors when they are
      expressed in the same cell. Although demonstrated in sensory neurons of the
      dorsal root ganglia, spinal cord and myenteric neurons, co-expression of
      cannabinoid type 1 and transient receptor potential vanilloid type 1 has not yet
      been studied in the brain. In the present study, we addressed this issue by using
      commercially available specific antibodies whose specificity was confirmed by
      data obtained with brains from cannabinoid type 1(-/-) and transient receptor
      potential vanilloid type 1(-/-) mice. Double cannabinoid type 1/transient
      receptor potential vanilloid type 1 immunofluorescence and single cannabinoid
      type 1 or transient receptor potential vanilloid type 1 avidin-biotin complex
      immunohistochemistry techniques were performed and both methods used point to the
      same results. Cannabinoid type 1/transient receptor potential vanilloid type 1
      expression was observed in the hippocampus, basal ganglia, thalamus,
      hypothalamus, cerebral peduncle, pontine nuclei, periaqueductal gray matter,
      cerebellar cortex and dentate cerebellar nucleus. In particular, in the
      hippocampus, cannabinoid type 1/transient receptor potential vanilloid type 1
      expression was detected on cell bodies of many pyramidal neurons throughout the
      CA1-CA3 subfields and in the molecular layer of dentate gyrus. In the cerebellar
      cortex, expression of cannabinoid type 1/transient receptor potential vanilloid
      type 1 receptors was found surrounding soma and axons of the vast majority of
      Purkinje cell bodies, whose cytoplasm was found unstained for both receptors.
      Cannabinoid type 1 and transient receptor potential vanilloid type 1
      immunoreactivity was also detected in: a) the globus pallidus and substantia
      nigra, in which some intensely transient receptor potential vanilloid type 1
      immunopositive cell bodies were found in dense and fine cannabinoid type
      1/transient receptor potential vanilloid type 1 positive and cannabinoid type 1
      positive nerve fiber meshworks, respectively; b) the cytoplasm of thalamic and
      hypothalamic neurons; and c) some neurons of the ventral periaqueductal gray.
      These data support the hypothesis of a functional relationship between the two
      receptor types in the CNS.

PMID- 16603319
TI  - Expression of discoidin domain receptor 1 during mouse brain development follows
      the progress of myelination.
AB  - Discoidin domain receptor 1 is a tyrosine kinase receptor expressed in a variety
      of tissues including the brain. This study describes mRNA and protein expression
      of discoidin domain receptor 1 in mouse brain during development and provides new
      insights into its role during gliogenesis and neurogenesis. We performed in situ
      hybridization for discoidin domain receptor 1 in mouse brains at embryonic day
      18, postnatal days 5, 9, 15, 21 and adulthood and observed a diffuse pattern in
      the proliferative areas during embryogenesis. From postnatal day 5 onwards, a
      defined cellular expression pattern of discoidin domain receptor 1 was observed,
      mainly located in white matter tracts and following a spatio-temporal pattern
      that overlapped the progress of myelination. Next, we performed double-labeling
      reactions (in situ hybridization followed by immunohistochemistry) that confirmed
      that discoidin domain receptor 1 was expressed by mature oligodendrocytes. We
      observed that cells positive for discoidin domain receptor 1 also expressed
      carnosine and anti-adenomatous polyposis coli, two mature oligodendrocyte
      markers. Based on the localization of discoidin domain receptor 1 specifically in
      the white matter fiber tracts during postnatal development, we suggest that
      discoidin domain receptor 1 participates in the development and maintenance of
      the myelin sheath.

PMID- 16603320
TI  - Population coding strategies and involvement of the superior colliculus in the
      tactile orienting behavior of naked mole-rats.
AB  - Even simple behaviors of vertebrates are typically generated by the concerted
      action of large numbers of brain cells. However, the mechanisms by which groups
      of neurons work together as functional populations to guide behavior remain
      largely unknown. One of the major model systems for exploring these mechanisms
      has been mammalian visuomotor behavior. We describe here experiments that
      establish a new model system for analyzing the sensory control of behavior by
      neuronal populations using a mammalian somatosensory response: orientation to
      touch cues in a rodent. We found that the CNS mechanisms used to direct these
      orientation responses to touch can be delineated from behavioral experiments. In
      this study we demonstrate that the superior colliculus, a component of the
      vertebrate midbrain most often thought of as a visual structure, is an essential
      component of the naked mole-rat's unique tactile orienting behavior. Furthermore,
      the information processing that underlies this behavior displays striking
      parallels with that used for visual orientation at anatomical and computational
      levels.

PMID- 16603321
TI  - Acculturation status and heavy alcohol use among Mexican American college
      students: investigating the moderating role of gender.
AB  - We examined whether gender moderates the association between acculturation and
      heavy alcohol use. The sample consisted of 126 Mexican American college students
      (Mean age=24.7 years; 57% female) who completed self-report measures of heavy
      alcohol use, acculturation status (global acculturation and ethnic identity), and
      relevant control variables (age, peer alcohol use). Multivariable regression
      revealed that higher levels of ethnic identity were associated with greater
      frequency of heavy alcohol among men. Conversely, neither measure of
      acculturation was associated with heavy alcohol use among women. These findings
      suggest that interventions for Latino/a students should consider the role of
      culturally relevant variables in heavy alcohol use, particularly for men. They
      also have implications regarding how acculturation is operationalized in alcohol
      studies, and suggest directions for future research.

PMID- 16603322
TI  - Cell mediated immunity to meet the avian influenza A (H5N1) challenge.
AB  - Avian influenza A subtype H5N1 virus with its recombination potential with the
      human influenza viruses presents a threat of producing a pandemic. The consensus
      is that the occurrence of such a pandemic is only a matter of time. This is of
      great concern, since no effective vaccine is available or can be made before the
      occurrence of the event. We present arguments for the use of cell mediated
      immunity for the prevention of the infection as well as for the treatment of
      infected patients. Transfer factor (TF), an immunomodulator of low molecular
      weight capable of transferring antigen-specific cell mediated immune information
      to T-lymphocytes, has been used successfully over the past quarter of a century
      for treating viral, parasitic, and fungal infections, as well as
      immunodeficiencies, neoplasias, allergies and autoimmune diseases. Moreover,
      several observations suggest that it can be utilised for prevention, transferring
      immunity prior to infection. Because it is derived from lymphocytes of immune
      donors, it has the potential to answer the challenge of unknown or ill-defined
      pathogens. Indeed, it is possible to obtain an antigen-specific TF preparation to
      a new pathogen before its identification. Thus, a specific TF to a new influenza
      virus can be made swiftly and used for prevention as well as for the treatment of
      infected patients.

PMID- 16603323
TI  - A sodium bicarbonate transporter from sea urchin spermatozoa.
AB  - Bicarbonate (HCO3-) transporters play crucial roles in cell-signaling pathways
      and are essential for cell viability. Here we describe the first cloning and
      localization of a HCO3- transporter from sperm of the sea urchin,
      Strongylocentrotus purpuratus. The deduced protein is 1214 amino acids and has a
      calculated molecular mass of 135 kDa. The annotated protein coding region of the
      transporter gene consists of 24 exons. The most similar human protein is the
      Na+/HCO3- cotransporter-2 (NBC2), which has 53% identity and 68% similarity to
      the sea urchin protein. The sea urchin protein shares the major structural
      features of HCO3- transporters, including 13 transmembrane segments, a DIDS (4,4
      diiodothiocyanatostilbene-2, 2-disulfonic acid) binding motif and N-linked
      glycosylation sites. It has longer N- and C-terminal cytoplasmic domains compared
      to human HCO3- transporters. The sea urchin protein possesses a relatively long
      3rd extracellular loop with four conserved cysteine residues. This is
      characteristic for Na+/HCO3- cotransporters, but not for anion exchangers,
      suggesting that the sea urchin protein is a Na+/HCO3- cotransporter. It is
      therefore designated as Sp-NBC. A neighbor-joining tree shows that Sp-NBC
      branches closer to the electroneutral type of HCO3- transporters. Western
      immunoblots and immunoflourescence show that Sp-NBC is concentrated in the
      flagellar plasma membrane, suggesting a role in motility regulation.

PMID- 16603324
TI  - Introduction: surgical conditions of the fetus and newborn.

PMID- 16603325
TI  - Fast cochlear amplification with slow outer hair cells.
AB  - In mammalian cochleas, outer hair cells (OHCs) produce mechanical amplification
      over the entire audio-frequency range (up to 100 kHz). Under the 'somatic electro
      motility' theory, mechano-electrical transduction modulates the OHC transmembrane
      potential, driving an OHC mechanical response which generates cycle-by-cycle
      mechanical amplification. Yet, though the OHC motor responds up to at least 70
      kHz, the OHC membrane RC time constant (in vitro upper limit approximately 1000
      Hz) reduces the potential driving the motor at high frequencies. Thus, the
      mechanism for high-frequency amplification with slow OHCs has been a two-decade
      long mystery. Previous models fit to experimental data incorporated slow OHCs but
      did not explain how the OHC time constant limitation is overcome. Our key
      contribution is showing that negative feedback due to organ-of-Corti functional
      anatomy with adequate OHC gain significantly extends closed-loop system bandwidth
      and increases resonant gain. The OHC gain-bandwidth product, not just bandwidth,
      determines if high-frequency amplification is possible. Due to the cochlea's
      collective traveling-wave architecture, a single OHC's gain need not be great.
      OHC piezoelectricity increases the effectiveness of negative-feedback but is not
      essential for amplification. Thus, emergent closed-loop network dynamics differ
      significantly from open-loop component dynamics, a generally important principle
      in complex biological systems.

PMID- 16603326
TI  - Vascular endothelial growth factor (VEGF) expression in noise-induced hearing
      loss.
AB  - Noise-induced hearing loss has been associated with alterations in cochlear blood
      flow. Our study analyzed the expression of Vascular Endothelial Growth Factor
      (VEGF) and its functional receptors, Flt-1 and Flk-1, in the cochlear structures
      of noise-exposed and unexposed guinea pigs. VEGF is a prototypical angiogenic
      agent, with multiple functions on vascular biology, ranging from vascular
      permeability to endothelial cell migration, proliferation, differentiation, and
      survival. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120
      dB SPL for 30 min. Auditory function was evaluated by electrocochleographic
      recordings at 2-20 kHz for 7 days. Noise-induced cochlear morphological changes
      were studied by immunohistochemistry and scanning electron microscopy. The
      expression of VEGF and its receptors was examined by immunohistochemistry and
      western blotting analysis. The hearing threshold shift reached a level of 60 dB
      SPL on day 1 after trauma and underwent a partial recovery over time, reaching a
      value of about 20 dB SPL on day 7. Outer hair cell loss was more prominent in the
      area located 14-16 mm from the apex. Increased cochlear VEGF expression was
      observed in noise-exposed animals, in particular at the level of stria
      vascularis, spiral ligament, and spiral ganglion cells. No changes were observed
      in the expression of VEGF-receptors. Our data suggest a role for VEGF in the
      regulation of the vascular network in the inner ear after acoustic trauma and
      during auditory recovery, with potentially important clinical and therapeutic
      implications.

PMID- 16603327
TI  - Cytotoxicity and in vitro susceptibility of Entamoeba histolytica to Morinda
      morindoides leaf extracts and its isolated constituents.
AB  - An aqueous decotion (dried extract), an 80% MeOH extract from Morinda morindoides
      leaves, and 10 flavonoids and 4 iridoids isolated from the 80% MeOH extract were
      evaluated in vitro for their potential antiamoebic activity and their cytotoxic
      effect against MT-4 cells. Results indicated that the aqueous decoction and the
      80% MeOH extract exhibited an interesting antiamoebic activity with IC(50) values
      of 3.1 +/- 1.7 and 1.7 +/- 0.6 microg/ml, respectively. Apigenin-7-O-glucoside
      and luteolin-7-O-glucoside exhibited a moderate antiamoebic activity with IC(50)
      values of 22.3 +/- 3.2 and 37.4 +/- 2.7 microg/ml, respectively. Kaempferol
      (IC(50) = 10.3 +/- 2.3 microg/ml), apigenin (IC(50) = 12.7 +/- 4.3 microg/ml),
      and luteolin (IC(50) = 17.8 +/- 4.3 microg/ml) showed a more pronounced activity
      than their corresponding glycosides. All tested iridoids displayed a very good
      activity with IC(50) values less than 10 microg/ml. The most active iridoids were
      epoxygaertneroside (IC(50) = 1.3 +/- 0.4 microg/ml) and methoxygaertneroside
      (IC(50) = 2.3. +/- 0.7), followed by gaertneroside and gaertneric acid with
      IC(50) values of 4.3 +/- 1.8 and 7.1 +/- 1.4 microg/ml, respectively. Except
      quercetin and quercetin-7,4'-dimethylether which have shown a cytotoxic effect
      with IC(50) ranging from 14 to 22 microg/ml. No correlation could be deduced
      between the observed antiamoebic and cytotoxic activity of these tested samples.
      A structure-activity relationship for isolated compounds is discussed. These
      findings support the medicinal report for the traditional use of Morinda
      morindoides leaves for the treatment of amoebiasis.

PMID- 16603328
TI  - Selective Th1 up-regulating activity of Withania somnifera aqueous extract in an
      experimental system using flow cytometry.
AB  - Withania somnifera (Ashwagandha) is reported to be immunoprotective and
      immunoadjuvant. We studied its roots aqueous extract on T helper (Th) immunity
      using flow cytometry. This extract was standardized with six withanolides as
      marker compounds using HPLC. Once daily dose ranging from 25 to 400 mg/kg/p.o.
      was used to study effect on Th1: IFN-gamma, IL-2 and Th2: IL-4 cytokine
      modulation. We also studied effect on CD4 and CD8 in normal and immunesuppressed
      mice. The results indicate that extract at 100 mg/kg resulted significant
      selective up-regulation of Th1 response. Treatment with extract showed
      significant increase in CD4 and CD8 counts as compared to control and cyclopsorin
      A, with a faster recovery of CD4+ T cells in immunesuppressed animals. Under
      immunesuppressed conditions, potentiation of cellular and humoral immune
      responses of extract was comparable to levamisole. This study indicates the
      selective Th1 up-regulating effect of extract and suggests its use for selective
      Th1/Th2 modulation.

PMID- 16603329
TI  - The mildest known case of Fukuyama-type congenital muscular dystrophy.
AB  - We present a 14-year-old boy with Fukuyama-type congenital muscular dystrophy
      (FCMD) who shows the mildest muscle weakness ever reported with this affliction
      and exceptionally mild mental retardation, but who has intractable epilepsy.
      Magnetic resonance imaging showed the typical abnormalities of FCMD. Molecular
      genetic analyses revealed a 3 kb insertion mutation in the fukutin gene
      heterozygously. We could find no mutation in the coding region of the fukutin
      gene in the chromosome without a 3 kb insertion. The most probable mechanism of
      clinical manifestation in this patient could be either a mutation in the
      noncoding regions of the fukutin gene on the chromosome without the ancestral
      founder haplotype of FCMD, or an error in the process of transcription or
      translation. Another possibility is the abnormalities in other genes involved in
      the glycosylation of alpha-dystroglycan, such as Fukutin-related protein and
      LARGE genes.

PMID- 16603330
TI  - Ultrafine needle CO2 splenoportography: a comparative investigation with
      transarterial portography and MR portography.
AB  - PURPOSE: To evaluate the safety and quality of CO2 splenoportography (CO2-SP) by
      comparison to 3-dimensional dynamic contrast-enhanced magnetic resonance
      portography (3D-DCE-MRP) and transarterial portography (TAP). MATERIALS AND
      METHODS: CO2-SP, 3D-DCE-MRP and TAP were performed within 3 days in 35 patients.
      CO2-SP was conducted with a 26G needle by puncture of spleen under fluoroscopy
      and/or ultrasound guidance. A fifty mm3 of CO2 was manually injected within 3s.
      The safety and the side effects of CO2-SP were assessed with a scoring system
      based on both the subjective feeling of patients questioned and the objective
      appearances of vital signs, electrocardiogram (ECG) and saturation of
      percutaneous blood oxygen (SpO2). The quality of the imaging was compared among
      the three groups using different methods by a scoring criterion based on
      visualization of the portal branches. RESULTS: Transient mild discomfortable
      reaction was present in 18 patients (51.4%). The scores measured for quality of
      portal vein branch visualization in the groups with CO2-SP, 3D-DCE-MRP and TAP
      were 226, 196 and 167, respectively (P<0.001, the higher of the scores, the
      better of the quality). The visibility of collateral veins was not significantly
      different amongst the three imaging techniques. CONCLUSION: Ultrafine needle CO2
      SP is safe and minimally invasive. The quality of CO2-SP is better than that with
      3D-DCE-MRP and TAP in terms of the visualizing portal vein branches.

PMID- 16603331
TI  - Prior experiences associated with residents' scores on a communication and
      interpersonal skill OSCE.
AB  - OBJECTIVE: This exploratory study investigated whether prior task experience and
      comfort correlate with scores on an assessment of patient-centered communication.
      METHODS: A six-station standardized patient exam assessed patient-centered
      communication of 79 PGY2-3 residents in Internal Medicine and Family Medicine. A
      survey provided information on prior experiences. t-tests, correlations, and
      multi-factorial ANOVA explored relationship between scores and experiences.
      RESULTS: Experience with a task predicted comfort but did not predict
      communication scores. Comfort was moderately correlated with communication scores
      for some tasks; residents who were less comfortable were indeed less skilled, but
      greater comfort did not predict higher scores. Female gender and medical school
      experiences with standardized patients along with training in patient-centered
      interviewing were associated with higher scores. Residents without standardized
      patient experiences in medical school were almost five times more likely to be
      rejected by patients. CONCLUSIONS: Task experience alone does not guarantee
      better communication, and may instill a false sense of confidence. Experiences
      with standardized patients during medical school, especially in combination with
      interviewing courses, may provide an element of "deliberate practice" and have a
      long-term impact on communication skills. PRACTICE IMPLICATIONS: The combination
      of didactic courses and practice with standardized patients may promote a patient
      centered approach.

PMID- 16603332
TI  - Peritoneal Surface Oncology: A progress report.
AB  - The Fourth International Workshop on Peritoneal Surface Malignancy took place in
      Madrid (Spain) on December 2, 3 and 4, 2004. The meeting brought together 132
      health care professionals currently working on or interested in the management of
      peritoneal surface malignancy, from 19 countries. The topics covered included
      diagnostic pathology, technology of hyperthermic peritoneal perfusion,
      quantitative prognostic indicators, accreditation of treatment programs, ovarian
      cancer, gastric cancer, peritoneal mesothelioma, appendiceal mucinous tumors,
      colorectal cancer, morbidity and mortality, and were presented by 25 invited
      speakers. This article summarizes the most significant discussion points and
      conclusions relative to the aforementioned topics. The following consensus points
      were reached: (1) cytoreductive surgery combined with perioperative
      intraperitoneal chemotherapy is unquestionably considered the standard of care
      for mucinous appendiceal tumors with peritoneal spread at the present time; (2)
      there is a need for standardization in the nomenclature used in this field and as
      a first step "HIPEC" was chosen as the recommended acronym to be used to refer to
      hyperthermic intraperitoneal chemotherapy in the future; (3) close international
      collaboration is needed to advance in the standardization of prognostic
      indicators, technology for HIPEC, accreditation of peritoneal surface malignancy
      treatment programs, anesthesia management and pathology, and ad hoc working
      groups were assembled for some of these issues. Future directions for clinical
      research in this field, especially in carcinomatosis of colorectal origin were
      identified and extensively discussed.

PMID- 16603333
TI  - [Disposable vs reusable laryngeal mask airway: a cost-minimization analysis].
AB  - JUSTIFICATION: According to French regulations concerning the risk of Creutzfeldt
      Jakob disease transmission, traceability procedures of all sterile medical
      devices which need to be reused are mandatory. Despite sterilization processes,
      the reusable laryngeal mask airway (LMA) prion disease transmission remains
      possible. As a result, the disposable LMA has been introduced. OBJECTIVE:
      Assuming clinical equivalence was achieved, the cost of disposable vs reusable
      LMA was studied in a university hospital. STUDY DESIGN: A Cost-minimization
      analysis of disposable vs reusable laryngeal mask airway was realised. METHODS:
      Disposable LMA cost was calculated as the sum of product cost and elimination
      cost. Reusable LMA were autoclaved after hospital purchasing in two separate
      sterilizing processing units of the same hospital. Reusable LMA cost was
      determined combining materiel and labor costs. RESULTS: The reusable LMA cost
      depended on the sterilizing processing unit concerned and varied between 9.59
      Euros and 9.69 vs 8.38 Euros for the single-use LMA. CONCLUSION: With the cost
      savings made possible by use of disposable LMA in both labor and consumables,
      this practice should be considered.

PMID- 16603334
TI  - A human-horse comparative map based on equine BAC end sequences.
AB  - In an effort to increase the density of sequence-based markers for the horse
      genome we generated 9473 BAC end sequences (BESs) from the CHORI-241 BAC library
      with an average read length of 677 bp. BLASTN searches with the BESs revealed
      4036 meaningful hits (E <or= 10(-5)) in the human genome that provide useful
      markers for the human-horse comparative map. The 4036 BLASTN hits allowed the
      anchoring of 3079 BAC clones to the human genome, on average one corresponding
      equine BAC clone per megabase of human DNA. We used the BLASTN anchored BESs for
      an in silico prediction of the gene content and chromosome assignment of
      comparatively mapped equine BAC clones. As a first verification of our in silico
      mapping strategy we placed 19 equine BESs with matches to HSA6 onto the RH map.
      All markers were assigned to the predicted localizations on ECA10, ECA20, and
      ECA31, respectively.

PMID- 16603335
TI  - Effects of carrageenan and morphine on acute inflammation and pain in Lewis and
      Fischer rats.
AB  - The present study used inbred, histocompatible Fischer 344 (FIS) and Lewis (LEW)
      rats to begin to explore the role of the hypothalamic-pituitary-adrenal (HPA)
      axis in the immune processes and pain behavior associated with the carrageenan
      model of acute hindpaw inflammation. Because the HPA axis contributes in part to
      morphine's analgesic and immunomodulatory properties, the present study also
      assessed the effects of morphine in carrageenan-inflamed LEW and FIS rats. The
      results showed that carrageenan-induced hindpaw swelling and pain behavior were
      greater in FIS than in LEW rats. The enhanced hindpaw swelling in FIS rats
      correlated with an increase in myeloperoxidase (MPO; a measure of neutrophils) in
      the inflamed hindpaw. FIS rats showed lower circulating levels of TNFalpha,
      higher IL-6 levels, and similar IL-1beta and nitric oxide levels, when compared
      to LEW rats. Morphine produced a significant decrease in carrageenan-induced
      hindpaw swelling and MPO in both strains, but morphine did not significantly
      alter circulating cytokine/mediator levels. Morphine's analgesic effects were
      greater in the inflamed than the noninflamed hindpaw, and they did not correlate
      with morphine's anti-inflammatory effects. In fact, low doses of morphine
      produced a mechanical allodynia and hyperalgesia in the noninflamed hindpaw of
      FIS, but not LEW, rats. These results suggest a positive relationship between HPA
      axis activity and acute inflammation and inflammatory pain. In contrast, little
      evidence is provided for HPA axis involvement in morphine's anti-inflammatory or
      analgesic effects.

PMID- 16603336
TI  - Acute psychotic symptoms in HIV-1 infected patients are associated with increased
      levels of kynurenic acid in cerebrospinal fluid.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection is associated with
      psychiatric complications including cognitive impairment, affective disorders,
      and psychosis. Previous studies have revealed a disturbed kynurenine metabolism
      in these patients leading to increased levels of neuroactive compounds acting at
      glutamatergic neurotransmission. Kynurenic acid (KYNA), one of these metabolites
      is a glutamate-receptor antagonist, preferentially blocking the glycine site of
      the N-methyl-d-aspartate (NMDA) receptor. Increased levels of brain KYNA have
      been suggested to induce a NMDA receptor hypofunction that is associated with
      psychotic symptoms. In the present study, we analyze the concentration of KYNA in
      the cerebrospinal fluid (CSF) from HIV-1 infected patients (n=22), including HIV
      1 infected patients with psychotic symptoms (n=8) and HIV-1 infected patients
      without psychiatric symptoms (n=14). We found that HIV-1 infected patients had
      significantly higher median concentration of CSF KYNA (3.02nM) compared to
      healthy controls (1.17nM). Furthermore, CSF KYNA levels were significantly
      elevated in HIV-1 infected patients with psychotic symptoms (4.54nM) compared to
      patients with HIV-1 without psychiatric symptoms (2.28nM). Present results
      indicate that increased levels of CSF KYNA may be associated with development of
      psychotic symptoms in HIV-1 infected patients.

PMID- 16603337
TI  - The effect of a parent-implemented imitation intervention on spontaneous
      imitation skills in young children with autism.
AB  - Children with autism exhibit significant deficits in their ability to
      spontaneously imitate the play actions and descriptive gestures of others.
      Reciprocal imitation training (RIT) is a naturalistic imitation intervention
      designed to teach spontaneous imitation skills during play. This study assessed
      the effectiveness of parent-implemented RIT using a multiple-baseline design
      across three young children with autism and their mothers. After an initial
      baseline, mothers were taught to implement RIT techniques with their child twice
      a week for 10 weeks in a clinic setting. Two mothers were taught to use RIT to
      teach object imitation. The third mother was taught to use RIT to target both
      object and gesture imitation in a multiple-baseline design across behaviors.
      Generalization was assessed in the families' homes at the end of treatment and a
      1-month follow-up. Parents learned to use the intervention strategies and their
      children exhibited increases in spontaneous imitation. These findings replicate
      the results from previous studies, indicating that RIT is effective for teaching
      imitation skills to young children with autism in a naturalistic setting and
      extend the findings to parents.

PMID- 16603338
TI  - Terminated Ramp-Support vector machines: a nonparametric data dependent kernel.
AB  - We propose a novel algorithm, Terminated Ramp-Support Vector Machines (TR-SVM),
      for classification and feature ranking purposes in the family of Support Vector
      Machines. The main improvement relies on the fact that the kernel is
      automatically determined by the training examples. It is built as a function of
      simple classifiers, generalized terminated ramp functions, obtained by separating
      oppositely labeled pairs of training points. The algorithm has a meaningful
      geometrical interpretation, and it is derived in the framework of Tikhonov
      regularization theory. Its unique free parameter is the regularization one,
      representing a trade-off between empirical error and solution complexity.
      Employing the equivalence between the proposed algorithm and two-layer networks,
      a theoretical bound on the generalization error is also derived, together with
      Vapnik-Chervonenkis dimension. Performances are tested on a number of synthetic
      and real data sets.

PMID- 16603339
TI  - A role for extracellular and transmembrane domains of Sef in Sef-mediated
      inhibition of FGF signaling.
AB  - Sef (similar expression to fgf genes) is a member of the fibroblast growth factor
      (FGF) synexpression group that negatively regulates FGF receptor (FGFR) signaling
      in zebrafish during early embryonic development and in mammalian cell culture
      systems. The mechanism by which Sef exerts its inhibitory effect remains
      controversial. It has been reported that Sef functions either through binding to
      and inhibiting FGFR1 activation or by acting downstream of FGF receptors at the
      level of MEK/ERK kinases. In both cases, the intracellular domain of Sef was
      found to play a role in the inhibitory function of Sef. Here we demonstrated that
      both extracellular and transmembrane domains of Sef contributed to Sef-mediated
      negative regulation of FGF signaling. In fact, over-expression studies in NIH3T3
      cells showed that a truncated mutant of Sef, which lacks the intracellular domain
      (SefECTM), exerted the inhibitory activity on FGF signaling by inhibiting FGFR1
      tyrosine phosphorylation and subsequent activation of the Raf/MEK/ERK signaling
      cascade. We also showed that SefECTM associated with FGFR1, and inhibited FGF
      induced ERK activation in HEK293T cells. Furthermore, we demonstrated that the
      over-expression of SefECTM was able to inhibit the function of a constitutively
      activated form of FGFR1, FGFR1-C289R, but not FGFR1-K562E. Finally, we found that
      SefECTM reduced cell viability when over-expressed in human umbilical vein
      endothelial cells (HUVEC). These data provide additional insight into the
      structure-activity relationship in the mechanism of inhibitory action of Sef on
      FGFR1-mediated signaling.

PMID- 16603340
TI  - X Chromosomal effects on social cognitive processing and emotion regulation: A
      study with Klinefelter men (47,XXY).
AB  - Studying Klinefelter syndrome (47,XXY), a genetically defined disorder
      characterized by the presence of an additional X chromosome, can reveal insights
      into genotype-phenotype associations. Increased vulnerability to psychiatric
      disorders characterized by difficulties in social interactions, such as
      schizophrenia and autism, has been reported for this population. The reported
      social difficulties in 47,XXY men may arise as a consequence of impairments in
      the processing of social and emotional information. The present study is the
      first investigation of social-emotional information processing in this X
      chromosomal disorder. 32 Klinefelter men and 26 men from the general population,
      with the groups matched for age, educational level and I.Q., participated in the
      study. Several tasks were included, reflecting aspects of social-emotional
      information processing on levels of perception, experience and expression:
      labeling of facial expressions of emotion, emotion-cognition interactions in
      decision making and emotion regulation, that refers to subjective experience and
      identification of emotional arousal as well as verbal expression of emotions. A
      discrepancy between cognitive appraisal of emotions and emotional arousal was
      observed in Klinefelter syndrome. Taken together, Klinefelter men seem less
      accurate in perception of socio-emotional cues such as angry facial expressions,
      they are less able to identify and verbalize their emotions, but experience
      increased levels of emotional arousal, in comparison to the general population.
      Besides describing the social-emotional phenotype of this X chromosomal disorder,
      the present data may prove to be an important contribution to the development of
      more general models describing pathways to neuropsychiatric disorders
      characterized by social cognitive disturbances.

PMID- 16603341
TI  - Correlation of PET and qEEG in normal subjects.
AB  - Positron emission tomography (PET) and quantitative electroencephalography (qEEG)
      were obtained in 15 normal male subjects with eyes closed at rest. Correlations
      between qEEG variables and regional metabolism were examined as an approach to
      investigating the metabolic and neuroanatomical basis of the generation of the
      EEG. Analogous to the neurometric approach to qEEG, a normative 2-fluoro
      deoxyglucose voxel data base was developed for the PET image. The PET image was
      transformed to an idealized cylindrical set of coordinates to allow registration
      with the Talairach stereotactic atlas. PET regions of interest for the thalamus,
      the left and right temporal lobes, the medial frontal cortex and the dorsolateral
      prefrontal cortex were defined using Talairach coordinates and correlated to the
      QEEG. Salient findings included a negative correlation of thalamic metabolism to
      alpha power and a positive correlation of medial frontal cortical metabolism to
      delta EEG power. The significance of these findings is discussed with reference
      to the existing literature on the physiology of the generation of the EEG.

PMID- 16603342
TI  - [Childhood obesity and early food experiences].
AB  - Authors insist on the role of early food experiences in the constitution of young
      child obesity. Obesity often appears precociously within the first two years of
      life. In many cases, it results from inappropriate feeding behaviors, behaviors
      of overfeeding deteriorating the mechanisms of energy regulation of the child.
      The prevention requires a work on the early baby/environment interactions.

PMID- 16603343
TI  - Immune synapses in T-cell activation.
AB  - The contact site between T cells and antigen-presenting cells or T cells and
      their targets--the immunological synapse--is a highly specialized structure
      potentially involved in T-cell activation and function. Although many insights
      have been obtained since the initial description of the immune synapse, recent
      advances have provided us with a better understanding of mechanisms involved in
      synapse formation and in the diversity of synapse morphologies. New potential
      roles for the synapse such as in polarized cytokine secretion or in adaptive
      control of T-cell activation have been proposed.

PMID- 16603344
TI  - The role of serine/threonine kinases in T-cell activation.
AB  - Signalling through serine/threonine kinases is a key mechanism that regulates
      immune cell development, activation and effector functions. An emerging theme is
      that serine kinases do not act in isolation, but function in a complex
      overlapping network. Understanding the molecular targets of serine kinases as
      well as their links to other serine kinases is key to advancing our understanding
      of the intracellular signalling pathways that link immune receptors with the gene
      transcriptional programs that control the immune system in vivo.

PMID- 16603345
TI  - Detection of colorectal cancer using MALDI-TOF serum protein profiling.
AB  - Serum protein profiling is a promising approach for classification of cancer
      versus non-cancer samples. The objective of our study was to assess the
      feasibility of mass spectrometry based protein profiling for the discrimination
      of colorectal cancer (CRC) patients from healthy individuals. In a randomized
      block design, pre-operative serum samples obtained from 66 colorectal cancer
      patients and 50 controls were used to generate MALDI-TOF protein profiles. After
      pre-processing of the spectra, linear discriminant analysis with double cross
      validation was used to classify protein profiles. A total recognition rate
      (92.6%), sensitivity (95.2%) and specificity (90.0%) for the detection of CRC
      were shown. The area under the curve of the classifier was 97.3%, and
      demonstrated the high, significant separation power of the classifier. Double
      cross-validation shows that classification can be attributed to information in
      the protein profile. Although preliminary, the high sensitivity and specificity
      indicate the potential usefulness of serum protein profiles for the detection of
      colorectal cancer.

PMID- 16603346
TI  - Activated ERK1/2 and phosphorylated oestrogen receptor alpha are associated with
      improved breast cancer survival in women treated with tamoxifen.
AB  - The aim of this study was to investigate the expression of activated
      (phosphorylated) ERK1/2, oestrogen receptor alpha phosphorylated at S118
      (ERalphaS118), and HER2 in primary breast cancer, and to make correlations with
      the outcome of tamoxifen therapy. We performed immunohistochemical analysis to
      determine the expression of HER2, ERalphaS118, and activated ERK1/2 in tumours
      obtained from 279 women with primary breast cancer. HER2 status was also
      estimated by fluorescence in situ hybridisation. We identified 108 women with
      ERalpha-positive tumours who had received adjuvant tamoxifen. Activated ERK1/2
      (pERK1/2) and ERalphaS118 were found to be associated with each other and with
      other factors correlated with good prognosis. HER2 was inversely associated with
      pERK1/2. Positive staining for pERK1/2 (particularly intense staining) indicated
      better relapse-free survival (P=0.05) and a trend towards better breast cancer
      corrected survival in women treated with tamoxifen. To conclude, this study shows
      that activated ERK1/2 and ERalphaS118 are associated with improved survival. The
      poorer outcome in HER2-positive women who receive adjuvant tamoxifen cannot be
      explained by the crosstalk between HER2 and ERalphaS118 via activated ERK1/2
      alone.

PMID- 16603347
TI  - Inter-conversion of 7alpha- and 7beta-hydroxy-dehydroepiandrosterone by the human
      11beta-hydroxysteroid dehydrogenase type 1.
AB  - The dehydroepiandrosterone (DHEA) 7alpha-hydroxylation in humans takes place in
      the liver, skin, and brain. These organs are targets for the glucocorticoid
      hormones where 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activates
      cortisone through its reduction into cortisol. The putative interference of
      7alpha-hydroxy-DHEA with the 11beta-HSD1-catalyzed reduction of cortisone into
      cortisol has been confirmed in preliminary works with human liver tissue
      preparations of the enzyme demonstrating the transformation of 7alpha-hydroxy
      DHEA into 7-oxo-DHEA and 7beta-hydroxy-DHEA. However, the large production of
      7beta-hydroxy-DHEA could not be explained satisfactorily. Therefore our objective
      was to study the role in the metabolism of oxygenated DHEA by recombinant human
      11beta-HSD1 expressed in yeast. The 7alpha- and 7beta-hydroxy-DHEA were each
      oxidized into 7-oxo-DHEA with quite dissimilar K(M) (70 and 9.5 microM,
      respectively) but at equivalent V(max). In contrast, the 11beta-HSD1-mediated
      reduction of 7-oxo-DHEA led to the production of both 7alpha- and 7beta-hydroxy
      DHEA with equivalent K(M) (1.1 microM) but with a 7beta-hydroxy-DHEA production
      characterized by a significantly greater V(max). The 7alpha-hydroxy-DHEA produced
      by the cytochrome CYP7B1 in tissues may exert anti-glucocorticoid effects through
      interference with the 11beta-HSD1-mediated cortisone reduction.

PMID- 16603348
TI  - P3 and P4 position analysis of vinyl ester pseudopeptide proteasome inhibitors.
AB  - Two small libraries of tripeptidic-based vinyl ester derivative proteasome
      inhibitors were synthesized and tested, starting with the Hmb-Val-Gln-Leu-VE
      prototype. The P3 and P4 positions were investigated with a complete set of amino
      acid residues, some of which showed remarkable selective inhibition of the
      trypsin-like (beta2) subunit. In both positions, aromatic and hydrophobic
      residues were preferred.

PMID- 16603349
TI  - Structure-activity studies of oxazolidinone analogs as RNA-binding agents.
AB  - We have synthesized and tested a series of novel 3,4,5-tri- and 4,5-disubstituted
      oxazolidinones for their ability to bind two structurally related T box
      antiterminator model RNAs. We have found that optimal binding selectivity is
      found in a small group of 4,5-disubstituted oxazolidinones.

PMID- 16603350
TI  - One-pot synthesis and SAR study of cis-2,6-dialkyl-4-chloro-tetrahydropyrans.
AB  - A series of cis-2,6-dialkyl-4-chloro-tetrahydropyrans were prepared by means of
      an iron(III)-catalyzed process. The in vitro antiproliferative activities were
      examined in the human solid tumor cell lines A2780, SW1573, and WiDr. The results
      show that the presence of bulky substituents favors the Prins cyclization leading
      to new products with better activity profile against all cell lines tested.

PMID- 16603351
TI  - A pyrimidine-pyrazolone nucleoside chimera with potent in vitro anti
      orthopoxvirus activity.
AB  - Synthetic hybridization of two privileged drug scaffolds, pyrazolone on the one
      hand and pyrimidine nucleoside on the other, resulted in the generation of two
      novel 5-substituted pyrimidine nucleosides with potent in vitro antiviral
      activity against two representative orthopoxviruses, vaccinia virus and cowpox
      virus.

PMID- 16603352
TI  - Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as
      inhibitors of receptor tyrosine kinases.
AB  - 3-Benzimidazol-2-yl-1H-indazole analogs were developed as inhibitors of receptor
      tyrosine kinases (RTK). The synthesis and SAR of this series is reported.

PMID- 16603353
TI  - Discovery of indole-containing tetracycles as a new scaffold for androgen
      receptor ligands.
AB  - A novel series of tetracyclic indoles have been designed, synthesized and
      evaluated as androgen receptor (AR) ligands. Studies of structure-activity
      relationships (SARs) were investigated, which led to some compounds in this
      series as strong binders to androgen receptors.

PMID- 16603354
TI  - 4-(Aminoalkylamino)-3-benzimidazole-quinolinones as potent CHK-1 inhibitors.
AB  - CHK-1 is one of the key enzymes regulating checkpoints in cellular growth cycles.
      Novel 4-(amino-alkylamino)-3-benzimidazole-quinolinones were prepared and assayed
      for their ability to inhibit CHK-1. These compounds are potent cell permeable CHK
      1 inhibitors and showed synergistic effect with a DNA-damaging agent,
      camptothecin.

PMID- 16603355
TI  - Isoquinoline-pyridine-based protein kinase B/Akt antagonists: SAR and in vivo
      antitumor activity.
AB  - The structure-activity relationships of a series of isoquinoline-pyridine-based
      protein kinase B/Akt antagonists have been investigated in an effort to improve
      the major short-comings of the lead compound 3, including poor pharmacokinetic
      profiles in several species (e.g., mouse i.v. t(1/2) = 0.3 h, p.o. F = 0%).
      Chlorination at C-1 position of the isoquinoline improved its pharmacokinetic
      property in mice (i.v. t(1/2) = 5.0 h, p.o. F = 51%) but resulted in >500-fold
      drop in potency. In a mouse MiaPaCa-2 xenograft model, an amino analog 10y
      significantly slowed the tumor growth, however was accompanied by toxicity.

PMID- 16603356
TI  - Kinesin spindle protein (KSP) inhibitors. Part 4: Structure-based design of 5
      alkylamino-3,5-diaryl-4,5-dihydropyrazoles as potent, water-soluble inhibitors of
      the mitotic kinesin KSP.
AB  - Molecular modeling in combination with X-ray crystallographic information was
      employed to identify a region of the kinesin spindle protein (KSP) binding site
      not fully utilized by our first generation inhibitors. We discovered that by
      appending a propylamine substituent at the C5 carbon of a dihydropyrazole core,
      we could effectively fill this unoccupied region of space and engage in a
      hydrogen-bonding interaction with the enzyme backbone. This change led to a
      second generation compound with increased potency, a 400-fold enhancement in
      aqueous solubility at pH 4, and improved dog pharmacokinetics relative to the
      first generation compound.

PMID- 16603357
TI  - Flexible synthesis and biological evaluation of novel 5-deoxyadenophorine
      analogues.
AB  - Adenophorine and its 5-deoxy analogue have been identified as natural iminosugars
      with efficient glycosidase inhibitory effects. The syntheses and biological
      evaluation of two new series of 5-deoxyadenophorine analogues in their racemic
      form are reported. The compounds 12e and 13d bearing a C11 and C7 alkyl chain,
      respectively, were found to be potent inhibitors of the beta-glucosidase from
      almond with Ki near to 60 microM. The compounds 13a,d which possess a 3,4-cis
      stereochemistry were efficient on glucosidases but also on the beta
      galactosidase, what was not observed with the 3,4-trans series 12.

PMID- 16603358
TI  - "You've got mail!": the role of e-mail in clinical breast surgical practice.
AB  - Easy Internet access is changing the practice of medicine in the US. At least 137
      million Americans have access to the World Wide Web, and up to one-half would
      like to communicate with their physicians by e-mail. The membership of the
      American Society of Breast Surgeons was surveyed to evaluate the current role of
      e-mail in patient-doctor relationships. Due to the extensive discussions often
      involved in the evaluation of breast disease, and the elective nature of most
      surgical procedures, this specialty may be particularly well-suited to using e
      mail communication as an extension of discussions during traditional office
      visits. A questionnaire was e-mailed to all members of the ASBS who had provided
      an e-mail address. About 1236 questionnaires were sent, and 285 surgeons
      responded, a 23% response rate. About 130 (46%) responders were female; 209
      responders (73%) did not use e-mail to communicate with patients (76% of
      responding females, 70% of males). The oldest and youngest surgeons were least
      likely to use e-mail to communicate with patients. There was no gender-related
      difference in e-mail use. There was no difference in e-mail use between surgeons
      who limit their practice to breast disease and those who do not. Urban and
      university-based surgeons were more likely to use e-mail. Medical-legal liability
      concerns and confidentiality issues were the most common reasons for not using e
      mail. Among those surgeons who did use e-mail, ability to answer at one's own
      discretion, and the ability to provide an organized response were the major
      reasons for using e-mail. Overall, the membership expressed a preference for
      personal interaction over electronic communication.

PMID- 16603359
TI  - Ammonia-oxidising Crenarchaeota: important players in the nitrogen cycle?
AB  - Cultivation-independent molecular surveys show that members of the kingdom
      Crenarchaeota within the domain Archaea represent a substantial component of
      microbial communities in aquatic and terrestrial environments. Recently,
      metagenomic studies have revealed that such Crenarchaeota contain and express
      genes related to those of bacterial ammonia monooxygenases. Furthermore, a marine
      chemolithoautotrophic strain was isolated that uses ammonia as a sole energy
      source. Considering the ubiquity and abundance of Crenarchaeota, these findings
      considerably challenge the accepted view of the microbial communities involved in
      global nitrogen cycling. However, the quantitative contribution of Archaea to
      nitrification in marine and terrestrial environments still remains to be
      elucidated.

PMID- 16603360
TI  - Protein identification and expression analysis using mass spectrometry.
AB  - The identification and quantification of the proteins that a whole organism
      expresses under certain conditions is a main focus of high-throughput proteomics.
      Advanced proteomics approaches generate new biologically relevant data and potent
      hypotheses. A practical report of what proteome studies can and cannot accomplish
      in common laboratory settings is presented here. The review discusses the most
      popular tandem mass-spectrometry-based methods and focuses on how to produce
      reliable results. A step-by-step description of proteome experiments is given,
      including sample preparation, digestion, labeling, liquid chromatography, data
      processing, database searching and statistical analysis. The difficulties and
      bottlenecks of proteome analysis are addressed and the requirements for further
      improvements are discussed. Several diverse high-throughput proteomics-based
      studies of microorganisms are described.

PMID- 16603361
TI  - Acute autonomic sensory and motor neuropathy associated with central nervous
      system disturbance.
AB  - We report a 45-year-old woman with acute autonomic sensory and motor neuropathy
      (AASMN) showing central nervous system (CNS) disturbance. She presented with
      disturbance of consciousness, complex partial seizures with automatisms,
      autonomic, sensory and motor neuropathy, showing severe orthostatic hypotension
      and neurogenic bladder. Nerve conduction studies and nerve biopsy indicated
      axonal degeneration involving both the myelinated and unmyelinated fibers. Muscle
      biopsy revealed neurogenic muscular atrophy. Electroencephalogram revealed theta
      wave activities and sharp wave abnormalities in the frontal lobe. Intravenous
      immunoglobulin therapy resulted in complete recovery of consciousness levels, but
      no obvious improvement of the other symptoms. Only eight patients with AASMN have
      been reported. This is the first report of AASMN showing CNS disturbance.
      Perivascular lymphocytic infiltration into the temporal lobe and brain stem was
      described in an autonomic neuropathy patient. An inflammatory pathogenesis of the
      CNS disturbance associated with this autonomic neuropathy was proposed.

PMID- 16603362
TI  - MAPK signal specificity: the right place at the right time.
AB  - Although the mechanisms that lead to activation of the Ras, extracellular-signal
      regulated kinase mitogen-activated protein kinase (Ras/ERK-MAPK) signaling
      pathway have been studied intensively, the fundamental principles that determine
      how activation of ERK signaling can result in distinct biological outcomes have
      only recently received attention. Factors such as cell-surface receptor density,
      expression of scaffolding proteins, the surrounding extracellular matrix, and the
      interplay between kinases and phosphatases modulate the strength and duration of
      ERK signaling. Furthermore, the spatial distribution and temporal qualities of
      ERK can markedly alter the qualitative and quantitative features of downstream
      signaling to immediate early genes (IEG) and the expression of IEG-encoded
      protein products. As a result, IEG products provide a molecular interpretation of
      ERK dynamics, enabling the cell to program an appropriate biological response.

PMID- 16603363
TI  - Epidemiology of athletic knee injuries: A 10-year study.
AB  - The knee is an anatomically and biomechanically complex joint. Few studies have
      been published reporting the type and frequency of knee injuries. However, this
      information that may help to prevent, diagnose, and treat knee joint injuries. We
      have documented 17,397 patients with 19,530 sport injuries over a 10-year period
      of time. 6434 patients (37%) had 7769 injuries (39.8%) related to the knee joint.
      68.1% of those patients were men and 31.6% were women. Almost 50% of the patients
      were between the ages of 20-29 (43.1%) at the time of injury. The injuries
      documented were ACL lesion (20.3%), medial meniscus lesion (10.8%), lateral
      meniscus lesion (3.7%), MCL lesion (7.9%), LCL lesion (1.1%), and PCL lesion
      (0.65%). The activities leading to most injuries were soccer (35%) and skiing
      (26%). LCL injury was associated with tennis and gymnastics, MCL with judo and
      skiing, ACL with handball and volleyball, PCL with handball, lateral meniscus
      with gymnastics and dancing, and medial meniscus with tennis and jogging.

PMID- 16603364
TI  - Synthesis and antibacterial activity of substituted flavones, 4-thioflavones and
      4-iminoflavones.
AB  - Synthesis of flavones, 4-thioflavones and 4-iminoflavones was carried out with
      the substitution of variable halogens, methyl, methoxy and nitro groups in the A,
      B and AB rings of the respective compounds and we also report here their
      antibacterial activity. Most of the synthesized compounds were found to be active
      against Escherichia coli, Bacillus subtilis, Shigella flexnari, Salmonella
      aureus, Salmonella typhi and Pseudomonas aeruginosa. Activity of 4-thioflavones
      and 4-iminoflavones was found to be higher than that of their corresponding
      flavone analogues. Investigated compounds having substituents like F, OMe and NO2
      at 4'-position in ring-B exhibited enhanced activity and the presence of
      electronegative groups in the studied compounds showed a direct relationship to
      the antibacterial activity.

PMID- 16603365
TI  - Synthesis of a library of polycationic lipid core dendrimers and their evaluation
      in the delivery of an oligonucleotide with hVEGF inhibition.
AB  - This article follows on from our previous work in the area of non-viral gene
      delivery using polycationic dendrimers (PCDs). Herein we report on the synthesis
      and efficacy of a new library of lipid core PCDs in the delivery of the anti
      angiogenic oligonucleotide (ODN-1) to retinal pigment epithelial cells. ELISA was
      used to monitor hVEGF levels in cells transfected with dendriplexes, Cytofectin
      GSV and control (non-transfected). At 48 h, hVEGF titres had returned to that of
      the untransfected control for Cytofectin GSV however, a number of dendriplexes
      continued to exhibit a marked reduction in hVEGF titres.

PMID- 16603367
TI  - Synthesis, study of 3D structures, and pharmacological activities of lipophilic
      nitroimidazolyl-1,4-dihydropyridines as calcium channel antagonist.
AB  - QSAR studies indicated that the potency of nifedipine analogues was dependent
      upon lipophilicity, an electronic term and separated terms for each position on
      the DHP ring. Changes in the substitution pattern at the C3, C4, and C5 positions
      of DHPs alter potency, tissue selectivity, and the conformation of the 1,4-DHP
      ring. In this project a group of alkyl ester analogues of new derivatives of
      nifedipine, in which the ortho-nitrophenyl group at position 4 is replaced by a 1
      methyl-5-nitro-2-imidazolyl substituent, and the methyl group at position 6 is
      replaced by a phenyl substituent, were synthesized and evaluated as calcium
      channel antagonist using the high K+ contraction of guinea-pig ileal longitudinal
      smooth muscle. The results for asymmetrical esters showed that lengthening of the
      substituent in C3 ester substituent increased activity. When increasing of the
      length is accompanied by increasing the hindrance, the activity decreased. The
      results demonstrate that all compounds were more active or similar in effect to
      that of the reference drug nifedipine.

PMID- 16603366
TI  - Evaluation of mismatch-binding ligands as inhibitors for Rev-RRE interaction.
AB  - Drugs targeting the stem-loop IIB of Rev responsible element (RRE) of HIV-1 mRNA
      are potential therapeutic agents for HIV-1 infection. The stem loop is
      characterized by an internal loop consist of consecutive G-G and G-A mismatches,
      which is the single binding site for Rev protein for nuclear export of viral
      mRNA. We report here that ligands binding to G-G and G-A mismatches in duplex DNA
      also bind to the internal loop in competition with Rev peptide and lead to the
      dissociation of pre-formed Rev-RRE complex in a model system.

PMID- 16603368
TI  - Design, synthesis, and biological activity of N6-substituted-4'-thioadenosines at
      the human A3 adenosine receptor.
AB  - A large series of N6-substituted-4'-thioadenosines were synthesized starting from
      D-gulonic-gamma-lactone, and structure-activity relationships were studied at the
      human A3 and other subtypes of adenosine receptors (ARs). 2-Chloro-substituted
      and 2-H analogues were compared. 2-Chloro-N6-methyl-4'-thioadenosine 19b was a
      highly potent and selective agonist (Ki=0.8+/-0.1 nM in binding) at the A3AR, and
      displayed the same relative efficacy in receptor activation as a known full
      agonist, Cl-IB-MECA. Most of N6-substituted-4'-thioadenosines were less potent in
      binding than the corresponding N6-substituted-adenosines or N6-substituted-4'
      thioadenosine-5'-uronamides. N6-(3-Iodobenzyl) derivative 19g was demonstrated to
      be an A3AR-selective partial agonist displaying a Ki value of 3.2 nM.

PMID- 16603369
TI  - Low-level activity measurement of 131Xem, 133Xem, 135Xe and 133Xe in atmospheric
      air samples using high-resolution dual X-gamma spectrometry.
AB  - High-resolution dual X and gamma spectrometry has been optimized to improve the
      sensitivity in analyzing radioxenon from environmental samples, especially for
      the metastable isotopes (131Xem and 133Xem). The full-energy peak (FEP)
      efficiency curve in the 20-700 keV range has been established with a global
      uncertainty better than +/-3% using a Monte Carlo simulation. The minimum
      detectable activity concentrations (MDC) achievable at the laboratory for 131Xem,
      133Xem, 133Xe and 135Xe are presented and the influence of 133Xe activity on the
      metastable radioxenon MDCs is evaluated.

PMID- 16603370
TI  - Activity measurement of a 176Lu sample using coincidence peaks and Monte Carlo
      simulations.
AB  - We present the results of the activity measurement of a sample of the rare
      isotope 176Lu, obtained by gamma-ray spectrometry through the use of 22 peaks in
      an energy spectrum acquired with a 300 cc well-type HPGe detector located in the
      Modane underground facility below the French Alps. Of the above peaks, 17 are
      coincidence peaks between two or three gamma-rays or X-rays. True coincidence
      summing corrections were made using our Coincal code. Monte Carlo simulations
      were carried out for calibration purposes.

PMID- 16603371
TI  - Systemic to pulmonary artery shunt in single ventricle.

PMID- 16603372
TI  - The influence of sialylation on glycan negative ion dissociation and energetics.
AB  - For the analysis of native glycans using tandem mass spectrometry (MS), it is
      desirable to choose conditions whereby abundances of cross-ring cleavages
      indicative of branch positions are maximized. Recently, negative ion tandem mass
      spectrometry has been shown to produce significantly higher abundances of such
      ions in glycans compared to the positive ion mode. Much of this prior work has
      concerned fragmentation patterns in asialo glycans. The present work compares the
      abundances of critical cross-ring cleavage ions using negative mode tandem mass
      spectrometry for milk oligosaccharides and N-linked glycans. For comparison,
      product ion formation was studied for deprotonated and nitrated ions formed from
      asialo glycans and deprotonated ions from sialylated glycans. Breakdown profiles
      demonstrate clearly that more energy was required to fragment sialylated
      compounds to the same extent as either their asialo or nitrate adducted
      counterparts. The extraction of a proton from a ring hydroxyl group during the
      ionization process may be viewed, qualitatively, as imparting significantly more
      energy to the ion than would that from a molecule bearing an acidic group, so
      that acidic glycans are more stable in the gas phase, as the negative charge
      resides on the carboxyl group. These results have strong practical implications
      because a major portion of glycans released from mammalian proteins will be
      sialylated.

PMID- 16603373
TI  - Decarboxylation of metastable methyl benzoate molecular ions.
AB  - By using a combination of mass spectrometric methodologies and density functional
      theory calculations [DFT/B3LYP/6-311 ++ G(d, p)], it is proposed that the
      decarboxylation of metastable methyl benzoate molecular ions occurs via distonic
      and ion-neutral complex (INC) intermediates. The same INC involving a complex
      between the benzyl radical and protonated carbon dioxide is also generated upon
      decarboxylation of metastable phenylacetic acid molecular ions. Internal proton
      transfer within the INC produces in fine a mixture of toluene and isotoluene
      radical cations.

PMID- 16603374
TI  - Incorporation of a flared inlet capillary tube on a fourier transform ion
      cyclotron resonance mass spectrometer.
AB  - Flared inlet capillary tubes have been coupled with a Fourier transform ion
      cyclotron resonance (FT-ICR) mass spectrometer to help the ion transmission from
      the atmospheric pressure to the first vacuum region. We investigated different
      types of atmospheric pressure ionization methods using flared inlet tubes. For
      most of the ionization methods, such as ESI and DESI, increased ion current
      transmitted from the atmospheric pressure ion source to the first stage vacuum
      system was observed with the use of our enhanced ion inlet designs. The
      corresponding ion intensity detected on a FT-ICR mass spectrometer was also
      observed to increase two- to fivefold using ESI or DESI with the flared tube
      inlet. Moreover, increased spray tip positional tolerance was observed with
      implementation of the flared inlet tube. We also include our preliminary results
      obtained by coupling AP-MALDI with flared inlet tube in this paper. For AP-MALDI,
      the measured ion current transferred through the flared inlet tube was about 2 to
      3 times larger than the ion current through the control non-flared inlet tube.

PMID- 16603375
TI  - On the risk of false positive identification using multiple ion monitoring in
      qualitative mass spectrometry: large-scale intercomparisons with a comprehensive
      mass spectral library.
AB  - Analysts involved in qualitative mass spectrometry have long debated the minimum
      data requirements for demonstrating that signals from an unknown sample are
      identical to those from a known compound. Often this process is carried out by
      comparing a few selected ions acquired by multiple ion monitoring (MIM), with due
      allowance for expected variability in response. In a few past experiments with
      electron-ionization mass spectrometry (EI-MS), the number of ions selected and
      the allowable variability in relative abundance were tested by comparing one
      spectrum against a library of mass spectra, where library spectra served to
      represent potential false positive signals in an analysis. We extended these
      experiments by carrying out large-scale intercomparisons between thousands of
      spectra and a library of one hundred thousand EI mass spectra. The results were
      analyzed to gain insights into the identification confidence associated with
      various numbers of selected ions. A new parameter was investigated for the first
      time, to take into account that a library spectrum with a different base peak
      than the search spectrum may still cause a false positive identification. The
      influence of peak correlation among the specific ions in all the library mass
      spectra was also studied. Our computations showed that (1) false positive
      identifications can result from similar compounds, or low-abundance peaks in
      unrelated compounds if the method calls for detection at very low levels; (2) a
      MIM method's identification confidence improves in a roughly continuous manner as
      more ions are monitored, about one order of magnitude for each additional ion
      selected; (3) full scan spectra still represent the best alternative, if
      instrument sensitivity is adequate. The use of large scale intercomparisons with
      a comprehensive library is the only way to provide direct evidence in support of
      these conclusions, which otherwise depend on the judgment and experience of
      individual analysts. There are implications for residue chemists who would rely
      on standardized confirmation criteria to assess the validity of a given
      confirmatory method. For example, standardized confirmation criteria should not
      be used in the absence of interference testing and rational selection of
      diagnostic ions.

PMID- 16603376
TI  - Use of the filter diagonalization method in the study of space charge related
      frequency modulation in fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - The filter diagonalization method (FDM) is a recently developed computational
      technique capable of extracting resonance frequencies and amplitudes from very
      short transient signals. Although it requires stable resonance frequencies and is
      slower than the fast Fourier transform (FFT), FDM has a resolution and accuracy
      that is unmatched by the FFT or any other comparable techniques. This unique
      feature of FDM makes it an ideal tool for tracing space charge induced frequency
      modulations in Fourier transform ion cyclotron resonance (FT-ICR) cells, which
      are shown to reach +/-400 ppm even for such simple spectra as Substance P.

PMID- 16603377
TI  - Tandem mass spectrometric analysis of a complex triterpene saponin mixture of
      Chenopodium quinoa.
AB  - A nano-HPLC electrospray ionization multi-stage tandem mass spectrometry (nLC-ESI
      MS/MS) approach was applied to a complex crude triterpene saponin extract of
      Chenopodium quinoa seed coats. In ESI-MS/MS spectra of triterpene saponins,
      characteristic fragmentation reactions are observed and allow the determination
      of aglycones, saccharide sequences, compositions, and branching. Fragmentation of
      aglycones provided further structural information. The chemical complexity of the
      mixture was resolved by a complete profiling. Eighty-seven triterpene saponins
      comprising 19 reported and 68 novel components were identified and studied by MS.
      In addition to four reported, five novel triterpene aglycones were detected and
      characterized according to their fragmentation reactions in ESI-MS/MS and
      electron ionization mass spectrometry (EI-MS). As a novelty fragmentation
      pathways were proposed and analyzed based upon quantum chemical calculations
      using a hybrid Hartree-Fock density functional method. Accuracy of the assignment
      procedure was proven by isolation and structure determination of a novel
      compound. As the relative distribution and composition of saponins varies between
      different cultivars and soils, the presented strategy allows a rapid and complete
      analysis of Chenopodium quinoa saponin distribution and composition, and is
      particularly suitable for quality control and screening of extracts designated
      for pharmaceutical, agricultural, and industrial applications.

PMID- 16603378
TI  - Overexpression and characterization of Wzz of Escherichia coli O86:H2.
AB  - O-Antigen plays a critical role in the bacterium-host interplay, the chain length
      is an important factor in O-antigen functions. Wzz protein is responsible for O
      antigen chain length regulation, but the mechanism is still unknown. Here, we
      overexpressed the Wzz of Escherichia coli O86:H2 in wzz mutant O86:H2 strain, the
      yield can achieve 15 mg/L. The recombinant Wzz was purified to 99% purity in
      dodecylmaltoside by sequential Ni-affinity chromatography and anion-exchange.
      Size exclusion chromatography and in vivo cross-linking experiments both showed
      that Wzz formed tetramer. Furthermore, analysis with circular dichroism revealed
      that the predominant structural composition in Wzz is alpha-helices, and
      incubation with O-antigen significantly changed Wzz conformation. The results
      suggested that Wzz protein can interact with O-antigen.

PMID- 16603379
TI  - Purification and characterization of the chaperone-like Hsp26 from Saccharomyces
      cerevisiae.
AB  - sHsps are ubiquitous ATP-independent molecular chaperones, which efficiently
      prevent the unspecific aggregation of non-native proteins. Here, we described the
      purification of the small heat shock protein Hsp26 from a Saccharomyces
      cerevisiae strain harboring a multicopy plasmid carrying HSP26 gene under the
      control of its native promoter. A 26 kDa protein was purified to apparent
      homogeneity with a recovery of 74% by a very reproducible three steps procedure
      consisting of ethanol precipitation, sucrose gradient ultracentrifugation, and
      heat inactivation of residual contaminants. The purified polypeptide was
      unequivocally identified as Hsp26 using a specific Hsp26 polyclonal antibody as a
      probe. The analysis of the purified protein by electron microscopy revealed near
      spherical particles with a diameter of 12.0 nm (n=57, standard deviation +/-1.6
      nm), displaying a dispersion in size ranging from 9.2 to 16.1 nm, identical to
      Methanococcus jannaschii Hsp16.5 and in the range of the size estimated for yeast
      Hsp26, in a previous report. Purified yeast Hsp26 was able to suppress 72% of the
      heat-induced aggregation of citrate synthase at a ratio of 1:1 (Hsp26 24-mer
      complex to citrate synthase dimer), and 86% of the heat-induced aggregation of
      lysozyme at a molar ratio of 1:16 (Hsp26 24-mer complex to lysozyme monomer). In
      conclusion, the Hsp26 protein purified as described here has structure and
      activity similar to the previously described preparations. As advantages, this
      new protocol is very reproducible and requires simple apparatuses which are found
      in all standard biochemistry laboratories.

PMID- 16603381
TI  - Expression in yeast and purification of a membrane protein, SERCA1a, using a
      biotinylated acceptor domain.
AB  - We have recently described the final steps leading to the crystallization of a
      mammalian membrane protein, the rabbit sarcoplasmic reticulum Ca2+-ATPase, after
      heterologous expression. Here, we detail the initial steps leading to this new
      purification method. A biotin acceptor domain was fused at the C-terminal part of
      Ca2+-ATPase and a thrombin site was inserted between both coding regions. The
      recombinant protein was expressed under the control of a galactose-inducible
      promoter in the yeast Saccharomyces cerevisiae. The biotinylation reaction of the
      protein was performed directly in vivo in yeast. After solubilization of the
      yeast light membrane fraction, the biotinylated protein was retained specifically
      using the strong biotin-avidin interaction. Finally, digestion by the protease
      thrombin allowed the separation of the Ca2+-ATPase from the biotinylated domain.
      At this step, Ca2+-ATPase is in a relatively purified form (about 40%). After a
      size-exclusion HPLC step, the purity of the protein is about 70%, and evaluation
      of the conformational changes during the catalytic cycle by monitoring the
      intrinsic fluorescence is demonstrated. The major advantage of this avidin
      procedure is the particularly good specific ATPase activity as compared with that
      of a purified His-tagged Ca2+-ATPase.

PMID- 16603380
TI  - Co-expression of multiple subunits enables recombinant SNAPC assembly and
      function for transcription by human RNA polymerases II and III.
AB  - Human small nuclear (sn) RNA genes are transcribed by either RNA polymerase II or
      III depending upon the arrangement of their core promoter elements. Regardless of
      polymerase specificity, these genes share a requirement for a general
      transcription factor called the snRNA activating protein complex or SNAP(C). This
      multi-subunit complex recognizes the proximal sequence element (PSE) commonly
      found in the upstream promoters of human snRNA genes. SNAP(C) consists of five
      subunits: SNAP190, SNAP50, SNAP45, SNAP43, and SNAP19. Previous studies have
      shown that a partial SNAP(C) composed of SNAP190 (1-514), SNAP50, and SNAP43
      expressed in baculovirus is capable of PSE-specific DNA binding and transcription
      of human snRNA genes by RNA polymerases II and III. Expression in a baculovirus
      system yields active complex but the concentration of such material is
      insufficient for many bio-analytical methods. Herein, we describe the co
      expression in Escherichia coli of a partial SNAP(C) containing SNAP190 (1-505),
      SNAP50, SNAP43, and SNAP19. The co-expressed complex binds DNA specifically and
      recruits TBP to U6 promoter DNA. Importantly, this partial complex functions in
      reconstituted transcription of both human U1 and U6 snRNA genes by RNA
      polymerases II and III, respectively. This co-expression system will facilitate
      the functional characterization of this unusual multi-protein transcription
      factor that plays an important early role for transcription by two different
      polymerases.

PMID- 16603382
TI  - An isolated Hda-clamp complex is functional in the regulatory inactivation of
      DnaA and DNA replication.
AB  - In Escherichia coli, a complex consisting of Hda and the DNA-loaded clamp-subunit
      of the DNA polymerase III holoenzyme promotes hydrolysis of DnaA-ATP. The
      resultant ADP-DnaA is inactive for initiation of chromosomal DNA replication,
      thereby repressing excessive initiations. As the cellular content of the clamp is
      10-100 times higher than that of Hda, most Hda molecules might be complexed with
      the clamp in vivo. Although Hda predominantly forms irregular aggregates when
      overexpressed, in the present study we found that co-overexpression of the clamp
      with Hda enhances Hda solubility dramatically and we efficiently isolated the Hda
      clamp complex. A single molecule of the complex appears to consist of two Hda
      molecules and a single clamp. The complex is competent in DnaA-ATP hydrolysis and
      DNA replication in the presence of DNA and the clamp deficient subassembly of the
      DNA polymerase III holoenzyme (pol III*). These findings indicate that the clamp
      contained in the complex is loaded onto DNA through an interaction with the pol
      III* and that the Hda activity is preserved in these processes. The complex
      consisting of Hda and the DNA-unloaded clamp may play a specific role in a
      process proceeding to the DnaA-ATP hydrolysis in vivo.

PMID- 16603383
TI  - Expression analysis of immune-relevant genes in the spleen of large yellow
      croaker (Pseudosciaena crocea) stimulated with poly I:C.
AB  - A SMART cDNA library from spleen of large yellow croaker (Pseudosciaena crocea)
      stimulated by poly I:C was constructed. A total of 1039 clones from the library
      were single-pass sequenced and compared with known sequences in the GenBank
      database. Of those expressed sequence tags (ESTs), 607 were identified as
      orthologs of known genes in the GenBank databases by Blast X search. Four hundred
      and thirty-two did not show significant homology with any known sequences in the
      public databases. These identified ESTs represented at least 252 different genes,
      which were categorised into nine groups according to their function. Of the
      identified genes, 159 genes (63.1%) shared homology with fish genes while 93
      (36.9%) showed the highest homology to the genes from other species. Forty-six
      genes were identified to be involved in immune functions, including complement
      system components, immunoglobulins, antigen processing and presentation proteins,
      interferon system proteins, cytokines, and some innate defence molecules. The
      most frequently occurring genes in this spleen cDNA library were hepcidin
      precursors represented by 46 ESTs, which were divided into five groups based on
      their putative amino acid sequences. The expression analysis of selected genes
      during polyI:C induction was performed by reverse transcription-PCR (RT-PCR),
      including Mx protein, beta2-microglobulin (beta(2)m), CD2 binding protein
      1(CD2BP1), placenta-specific 8 genes, MHC class II associated invariant chain
      (li) and cytochrome b-245 alpha peptide (Cyba). The results revealed that
      expression levels of Mx protein, beta(2)m, placenta-specific 8 genes, and Cyba
      were significantly upregulated at 30h after induction with poly I:C, and the
      CD2BP1 expression was also induced by polyI:C, suggesting that these genes may be
      involved in an immune response induced by poly I:C in large yellow croaker.

PMID- 16603384
TI  - The reaction strategy of lower extremity muscles when slips occur to individuals
      with trans-femoral amputation.
AB  - The aim of this study is to investigate the surface electromyography (sEMG)
      responses of lower extremity muscles for both healthy people and individuals with
      trans-femoral amputation (TFA), when slip events occur during level walking. Six
      male individuals with unilateral TFA and five healthy subjects participated in
      this study. Each subject was required to walk at a self-selected comfortable pace
      along a 5m plastic walkway, and to perform walking trials on dry and oily
      conditions respectively. The sEMG signals of muscles on legs and around waist
      were recorded in each trial and the normalized instantaneous muscle power (IMP)
      values were employed to quantify the response intensity. The IMP profiles of each
      muscle in oily-surface walking trials were compared quantitatively with that in
      dry-surface trials. There are three main findings in this study. (1) Different
      muscle reaction strategies are employed in slip events by the healthy persons and
      the individuals with TFA, respectively. Moreover, when the slip event occurs on
      the prosthetic leg and the intact leg of the individuals with TFA respectively,
      the muscle reaction strategies are also different. (2) The individuals with TFA
      face higher risks of fall than the healthy persons no mater slips occur on the
      prosthetic side or the intact side. (3) The hip muscles, especially the gluteus
      maximus (GMA) muscles, always enormously contribute to posture adjustment and
      balance recovery in slip events.

PMID- 16603385
TI  - Kinesiological surface electromyography in normal children: range of normal
      activity and pattern analysis.
AB  - To document the range of activity and patterns of normal surface kinesiological
      electromyography in normal children, 87 children ranging from age 3 to 18 years
      who were developing normally were evaluated at free walking speed. Analysis was
      performed on 6307 gait cycles from 11 different muscles with custom software. We
      devised an algorithm to do a computer-based KEMG curve pattern analysis to sort
      out curves that did not match the physiologic muscle activity pattern, We also
      devised a combined preset amplitude and statistics-based criteria to
      satisfactorily determine the onset/cessation of KEMG activity. The measurements
      of timing and duration of activity, body height and weight, body mass index,
      cadence, stride length, and age were obtained for statistical analysis. From the
      pattern recognition, the medial and lateral hamstrings, gluteus maximus and
      medius, and gastrocnemius muscles had the highest percentage of clinically
      relevant curves. In most muscle groups, The KEMG curves had an average background
      activity of about 11-15% of maximum amplitude. The surface KEMG curves from
      normal subjects have 12.7% cycles that did not match their physiologic activity
      pattern. The timing and duration of KEMG activity was poorly or only fairly
      correlated with age, body height, body weight, and body mass index. The ensemble
      average of the linear envelope KEMG curves of each muscle could be applied as a
      normal database in a clinical gait analysis laboratory focusing on pediatric
      patients.

PMID- 16603386
TI  - The mechanomyography of persons after stroke during isometric voluntary
      contractions.
AB  - This study was to investigate the properties of mechanomyography (MMG), or muscle
      sound, of the paretic muscle in the affected side of hemiplegic subjects after
      stroke during isometric voluntary contractions, in comparison with those from the
      muscle in the unaffected side of the hemiplegic subjects and from the healthy
      muscle of unimpaired subjects. MMG and electromyography (EMG) signals were
      recorded simultaneously from the biceps brachii muscles of the dominant arm of
      unimpaired subjects (n=5) and the unaffected and affected arms of subjects after
      stroke (n=8), when performing a fatiguing maximal voluntary contraction (MVC)
      associated with the decrease in elbow flexion torque, and then submaximal elbow
      flexions at 20%, 40%, 60% and 80% MVCs. The root mean squared (RMS) values, the
      mean power frequencies (MPF, in the power density spectrum, PDS) of the EMG and
      MMG, and the high frequency rate (HF-rate, the ratio of the power above 15Hz in
      the MMG PDS) were used for the analysis. The MMG RMS decreased more slowly during
      the MVC in the affected muscle compared to the healthy and unaffected muscles. A
      transient increase could be observed in the MMG MPFs from the unaffected and
      healthy muscles during the MVC, associated with the decrease in their
      simultaneous EMG MPFs due to the muscular fatigue. No significant variation could
      be seen in the EMG and MMG MPFs in the affected muscles during the MVC. The
      values in the MPF and HF-rate of MMG from the affected muscles were significantly
      lower than those from the healthy and unaffected muscles (P<0.05) at the high
      contraction level (80% MVC). Both the MMG and EMG RMS values in the healthy and
      unaffected groups were found to be significantly higher than the affected group
      (P<0.05) at 60% and 80% MVCs. These observations were related to an atrophy of
      the fast-twitch fibers and a reduction of the neural input in the affected
      muscles of the hemiplegic subjects. The results in this study suggested MMG could
      be used as a complementary to EMG for the analysis on muscular characteristics in
      subjects after stroke.

PMID- 16603387
TI  - Reduction in V1 activation associated with decreased visibility of a visual
      target.
AB  - The perception of a brief visual target stimulus can be affected by another
      visual mask stimulus immediately preceding or following the target. The link of
      this visual masking illusion, with visual cortical activation, offers insights
      into the neural mechanisms for visual perception. The present study investigated
      the association of the visibility of a target with cortical activation in humans
      using psychophysical testing and functional magnetic resonance imaging (fMRI). A
      visual masking protocol that was suitable for an fMRI study was developed. The
      event-related fMRI was used to measure activation in primary visual cortex (V1)
      during visual masking and unmasking stimulation. We found that the visibility of
      the target stimulus was reduced in the masking condition, due to the presence of
      mask stimuli, but not in the unmasking condition. We also found that the
      activation in V1 was modulated by the temporal separation of the mask stimuli
      from the target and was associated with the visibility of the target that was
      recorded during psychophysical testing and fMRI. These findings are consistent
      with what has been observed in the primate visual cortex of monkeys, i.e., the
      transient on-response and after-discharge of V1 neurons to the target stimulus
      were suppressed by forward and backward mask stimuli, respectively.

PMID- 16603388
TI  - Historical population dynamics and demography of the Eastern Atlantic pomacentrid
      Chromis limbata (Valenciennes, 1833).
AB  - Recent studies have focused on the relationship between the marine fauna of the
      Eastern Atlantic and the Mediterranean Sea, but within the Atlantic, little is
      known about genetic relationships between populations of the Macaronesian
      islands. In this study, we tested whether the paleo-climatology and paleo
      oceanography of the region could predict the genetic relationships among three
      Eastern Atlantic populations (Azores, Madeira, and Canaries) of a damselfish,
      Chromis limbata, and compared our results with its Mediterranean and adjacent
      Atlantic sister species, Chromis chromis. We combined phylogeographic and
      coalescent approaches using the fast evolving mitochondrial control region gene.
      No population structure was found for the three archipelagos. The coalescence
      time estimated for C. limbata (0.857-1.17 Mya) was much greater than that
      estimated for C. chromis. We propose that this difference reflects differences in
      glaciating extents in the Northeastern Atlantic and the Mediterranean. Diversity
      indexes (Hd and genetic distances) together with historical demographic
      parameters of C. limbata (Theta and g) revealed a more stable population history
      when compared to C. chromis. Our results suggest that the Macaronesian
      populations of C. limbata have probably been less affected by the last glaciation
      than the Mediterranean populations of C. chromis. Migration across the three
      archipelagos was estimated and a prevailing northwest trend was detected. This
      result supports the idea of a colonization of the Azores by warm water fish from
      Madeira or the westernmost Canary islands which acted as major glacial refugia
      for the tropical and subtropical marine fauna during the glaciations.

PMID- 16603389
TI  - Round and pointed-head grenadier fishes (Actinopterygii: Gadiformes) represent a
      single sister group: evidence from the complete mitochondrial genome sequences.
AB  - The gene order of mitochondrial genomes (mitogenomes) has been employed as a
      useful phylogenetic marker in various metazoan animals, because it may represent
      uniquely derived characters shared by members of monophyletic groups. During the
      course of molecular phylogenetic studies of the order Gadiformes (cods and their
      relatives) based on whole mitogenome sequences, we found that two deep-sea
      grenadiers (Squalogadus modificatus and Trachyrincus murrayi: family Macrouridae)
      revealed a unusually identical gene order (translocation of the tRNA(Leu (UUR))).
      Both are members of the same family, although their external morphologies
      differed so greatly (e.g., round vs. pointed head) that they have been placed in
      different subfamilies Macrouroidinae and Trachyrincinae, respectively.
      Additionally, we determined the whole mitogenome sequences of two other species,
      Bathygadus antrodes and Ventrifossa garmani, representing a total of four
      subfamilies currently recognized within Macrouridae. The latter two species also
      exhibited gene rearrangements, resulting in a total of three different patterns
      of unique gene order being observed in the four subfamilies. Partitioned Bayesian
      analysis was conducted using available whole mitogenome sequences from five
      macrourids plus five outgroups. The resultant trees clearly indicated that S.
      modificatus and T. murrayi formed a monophyletic group, having a sister
      relationship to other macrourids. Thus, monophyly of the two species with
      disparate head morphologies was corroborated by two different lines of evidence
      (nucleotide sequences and gene order). The overall topology of the present tree
      differed from any of the previously proposed, morphology-based phylogenetic
      hypotheses.

PMID- 16603390
TI  - Cost-effectiveness analysis of screening for abdominal aortic aneurysms based on
      five year results from a randomised hospital based mass screening trial.
AB  - BACKGROUND: The aim of this study was to estimate the cost effectiveness of
      screening for abdominal aortic aneurysm (AAA). MATERIAL AND METHODS: All 12,639
      men born in the years 1921-1933 (aged 64-73) living in Viborg County, Denmark,
      were randomly allocated either to receive an invitation to abdominal ultrasound
      scanning for AAA or to be controls. Costs for screening and surveillance were
      assessed prospectively. Diagnosis Related Group (DRG) costs from 1999 were used
      concerning admissions with uncomplicated and complicated operations. Admissions
      for AAA surgery were retrospectively classified according to complications in
      patient records. RESULTS: Mean follow-up time was 52 months. 76.6% of invited men
      attended screening, and 191 (4.0%) had an AAA. As previously reported, the
      cumulative 5-year AAA-specific mortality in the invited group was significantly
      reduced by 67% compared to the control group (P = 0.003). The costs were
      estimated to be Euro 11.23 per scan. The costs per life-year saved were Euro 9057
      (Euro 5872-20,063) after 5 years, and were expected to decrease to Euro 2708
      (Euro 1758-6031) after 10 years and to Euro 1825 (Euro 1185-4063) after 15 years.
      CONCLUSION: Screening of 64-73 years old males in Denmark seems cost effective.

PMID- 16603391
TI  - Analysis of the regulation, expression, and localisation of the isocitrate lyase
      from Aspergillus fumigatus, a potential target for antifungal drug development.
AB  - Invasive aspergillosis, caused by Aspergillus fumigatus, is a severe systemic
      infection in immunocompromised patients. New drug targets are required, since
      therapeutic treatment often fails and is hampered by severe side effects of
      antifungals. Enzymes of the glyoxylate bypass are potential targets, since they
      are absent in humans, but required for growth of Aspergillus on C2-generating
      carbon sources. The key enzyme isocitrate lyase (ICL) can be inhibited by 3
      nitropropionate, both as a purified enzyme and within intact cells, whereas the
      latter inhibition upregulates ICL promoter activity. ICL was found in distinct
      subcellular structures within growing hyphae, but only under conditions requiring
      ICL activity. In contrast, ICL was constitutively found in conidia, suggesting a
      specific role during germination. Lipids, as potential substrates, were detected
      in conidia and macrophages. Additionally, germinating conidia within macrophages
      contain ICL, suggesting that the glyoxylate shunt might be a relevant target for
      development of antifungals.

PMID- 16603392
TI  - Can a sexually dimorphic index of prenatal hormonal exposure be used to examine
      cold pressor pain perception in men and women?
AB  - There is considerable evidence to suggest that important differences exist
      between men and women in their experience of pain. Research has now turned to
      determine what the mechanisms of such differences actually are. One potential
      explanation is the effect of sex hormones, especially those typically found in
      greater concentration within women, e.g., estrogen, progesterone. However, it is
      also possible that other hormones, such as testosterone may be important. The
      current study employed a non-invasive sexually dimorphic index (digit ratio) that
      is believed to reflect prenatal exposure to testosterone, and related this to the
      cold pressor pain experiences of 23 men and 27 healthy women. As expected,
      females had greater symmetry between the second and fourth digits, and also
      reported lower pain tolerance levels. Although some significant relationships
      were found between digit ratio/digit length and cold pressor pain reports they
      were relatively inconsistent. Furthermore, the main finding, that pain thresholds
      were positively related to digit ratio in women but not men, is somewhat
      inconsistent with predictions. The results are discussed in light of methods for
      investigating the effect of prenatal hormonal exposure on pain sensitivity in men
      and women.

PMID- 16603393
TI  - Exposure and acceptance in the rehabilitation of adolescents with idiopathic
      chronic pain - a pilot study.
AB  - For chronic pain of unclear origin (idiopathic), pharmacological therapy is often
      insufficient. Psychological treatment strategies have been developed and
      evaluated for adults with chronic pain. However, few such studies are seen with
      youths, and to date there is limited empirical evidence regarding the
      effectiveness of psychological treatment for generalized musculoskeletal pain
      syndromes in adolescents. Acceptance and commitment therapy (ACT) is a
      development of cognitive behaviour therapy emphasizing exposure and acceptance.
      In this pilot study, 14 adolescents referred to the pain treatment service due to
      chronic debilitating pain were treated using an ACT-based approach. It was
      hypothesized that avoidance of pain and related stimuli was central to the
      disability seen among these patients, and that exposure and acceptance strategies
      could increase functioning and decrease pain. In contrast to emphasizing
      reductions in pain and distress, the treatment objective was to improve
      functioning by increasing the patient's ability to act in line with personal
      values in the presence of negative thoughts, emotions or bodily sensations.
      Following treatment, and retained at 3- and 6-month follow-up, improvements in
      functional ability, school attendance, catastrophizing and pain (i.e., intensity
      and interference) were seen. The outcome of this pilot study indicates that
      exposure and acceptance can been useful in the rehabilitation of adolescents with
      chronic debilitating pain. Randomized controlled studies are needed to
      empirically evaluate the effectiveness of this approach.

PMID- 16603394
TI  - Permeability of the haemolymph-neural interface in the terrestrial snail
      Megalobulimus abbreviatus (Gastropoda, Pulmonata): an ultrastructural approach.
AB  - The aim of this study was to investigate the ultrastructure of the interface zone
      between the nervous tissue and the connective vascular sheath that surround the
      central ganglia of the terrestrial snail of Megalobulimus abbreviatus and test
      its permeability using lanthanum as an electron dense tracer. To this purpose,
      ganglia from a group of snails were fixed by immersion in a 2% colloidal
      lanthanum solution, and a second group of animals was injected in the foot with
      either a 2%, 10% or 20% lanthanum nitrate solution and then sacrificed 2 or 24 h
      after injection. Ganglia from both groups were processed for transmission
      electron microscopy. The vascular endothelium, connective tissue and basal lamina
      of variable thickness that ensheathe the nervous tissue and glial cells of the
      nervous tissue constitute the interface zone between the haemolymph and the
      neurones. The injected lanthanum reached the connective tissue of the perineural
      capsule; however, it did not permeate into the nervous tissue because the basal
      lamina interposed between both tissues interrupted this passage. Moreover, the
      ganglia fixed with colloidal lanthanum showed electron dense precipitates between
      the glial processes in the area adjacent to the basal lamina. It can be concluded
      from these findings that, of the different components of the haemolymph-neuronal
      interface, only the basal lamina, between the perineural capsule and the nervous
      tissue, limits the traffic of substances to and from the central nervous system
      of this snail.

PMID- 16603395
TI  - Haemoconcentration via diuresis in short-term hypoxia: a possible role for
      cardiac natriuretic peptide in rainbow trout.
AB  - Rainbow trout, exposed to acute hypoxia (decrease of oxygen level from full to
      30% air saturation for 1 h, stable 30% air saturation for 2 h), showed more than
      twofold increase in urine flow rate. Hypoxic diuresis was associated with a
      sustained increase in dorsal aortic cardiac peptide (sCP) level, and the diuresis
      could be completely inhibited by a bolus injection of sCP antiserum. These
      results suggest that hypoxic haemoconcentration, which is partially achieved via
      increased urine flow rate in vertebrates, is caused by cardiac peptides. The
      results further suggest that cardiac peptide receptors in hypoxic fish gills
      modulate the postbranchial systemic level of sCP.

PMID- 16603396
TI  - Altered expression of master regulatory genes of adipogenesis in lipomas from
      patients bearing tRNA(Lys) point mutations in mitochondrial DNA.
AB  - The mechanisms underlying the appearance of lipomas in patients bearing mutations
      in the tRNA(Lys) gene of mitochondrial DNA are unknown. We investigated changes
      in gene expression patterns in lipomas from three patients bearing A8344G or
      G8363A tRNA(Lys) gene mutations. Uncoupling protein-1 mRNA was detected in the
      lipomas, in contrast with undetectable expression in normal adipose tissue.
      However, expression of other markers of brown fat, such as PGC-1alpha, was
      unaltered. PPARgamma and retinoblastoma gene expression was down regulated in the
      lipomas, but C/EBPalpha mRNA was not affected. The expression of Pref-1 was
      dramatically down regulated. Thus, lipomatosis due to tRNA(Lys) mutations is
      associated with a pattern of altered expression of master regulators of
      adipogenesis consistent with enhanced proliferation but maintenance of adipocyte
      features, and with a distorted pattern of brown versus white adipocyte
      differentiation.

PMID- 16603397
TI  - Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB.
AB  - The drug rapamycin has important uses in oncology, cardiology, and
      transplantation medicine, but its clinically relevant molecular effects are not
      understood. When bound to FKBP12, rapamycin interacts with and inhibits the
      kinase activity of a multiprotein complex composed of mTOR, mLST8, and raptor
      (mTORC1). The distinct complex of mTOR, mLST8, and rictor (mTORC2) does not
      interact with FKBP12-rapamycin and is not thought to be rapamycin sensitive.
      mTORC2 phosphorylates and activates Akt/PKB, a key regulator of cell survival.
      Here we show that rapamycin inhibits the assembly of mTORC2 and that, in many
      cell types, prolonged rapamycin treatment reduces the levels of mTORC2 below
      those needed to maintain Akt/PKB signaling. The proapoptotic and antitumor
      effects of rapamycin are suppressed in cells expressing an Akt/PKB mutant that is
      rapamycin resistant. Our work describes an unforeseen mechanism of action for
      rapamycin that suggests it can be used to inhibit Akt/PKB in certain cell types.

PMID- 16603398
TI  - Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and
      polyubiquitin binding by NEMO.
AB  - The receptor interacting protein kinase 1 (RIP1) is essential for the activation
      of nuclear factor kappaB (NF-kappaB) by tumor necrosis factor alpha (TNFalpha).
      Here, we present evidence that TNFalpha induces the polyubiquitination of RIP1 at
      Lys-377 and that this polyubiquitination is required for the activation of
      IkappaB kinase (IKK) and NF-kappaB. A point mutation of RIP1 at Lys-377 (K377R)
      abolishes its polyubiquitination as well as its ability to restore IKK activation
      in a RIP1-deficient cell line. The K377R mutation of RIP1 also prevents the
      recruitment of TAK1 and IKK complexes to TNF receptor. Interestingly,
      polyubiquitinated RIP1 recruits IKK through the binding between the polyubiquitin
      chains and NEMO, a regulatory subunit of the IKK complex. Mutations of NEMO that
      disrupt its polyubiquitin binding also abolish IKK activation. These results
      reveal the biochemical mechanism underlying the essential signaling function of
      NEMO and provide direct evidence that signal-induced site-specific ubiquitination
      of RIP1 is required for IKK activation.

PMID- 16603399
TI  - Feline primary hyperoxaluria.

PMID- 16603400
TI  - Population characteristics of feral cats admitted to seven trap-neuter-return
      programs in the United States.
AB  - Internationally, large populations of feral cats constitute an important and
      controversial issue due to their impact on cat overpopulation, animal welfare,
      public health, and the environment, and to disagreement about what are the best
      methods for their control. Trap-neuter-return (TNR) programs are an increasingly
      popular alternative to mass euthanasia. The objective of this study was to
      determine the population characteristics of feral cats admitted to large-scale
      TNR programs from geographically diverse locations in the United States. Data
      from 103,643 feral cats admitted to TNR programs from 1993 to 2004 were
      evaluated. All groups reported more intact females (53.4%) than intact males
      (44.3%); only 2.3% of the cats were found to be previously sterilized. Overall,
      15.9% of female cats were pregnant at the time of surgery. Pregnancy was highly
      seasonal and peaked between March and April for all of the groups. The average
      prenatal litter size was 4.1+/-0.1 fetuses per litter. Cryptorchidism was
      observed in 1.3% of male cats admitted for sterilization. A total of 0.4% of cats
      was euthanased because of the presence of debilitating conditions, and 0.4% died
      during the TNR clinics. Remarkably similar populations of cats with comparable
      seasonal variability were seen at each program, despite their wide geographical
      distribution. These results suggest that it is feasible to safely sterilize large
      numbers of feral cats and that the experiences of existing programs are a
      consistent source of information upon which to model new TNR programs.

PMID- 16603401
TI  - Ageing changes in cat brains demonstrated by beta-amyloid and AT8-immunoreactive
      phosphorylated tau deposits.
AB  - The life expectancy of domestic pet cats is increasing, along with the occurrence
      of geriatric-onset behavioural problems, such as cognitive dysfunction syndrome
      (CDS). While the cause of CDS is unclear, it has been suggested that it may
      result from age-related neurodegeneration. In aged and in particular senile human
      beings, histopathological changes may include the extracellular accumulation of
      plaque-like deposits of beta-amyloid (Abeta) protein and the intracellular
      accumulation of an abnormally hyperphosphorylated form of the microtubule
      associated protein, tau. In severe cases, the latter may form into
      neurofibrillary tangles. Brain material was assessed from 19 cats, aged from 16
      weeks to 14 years; 17 of which had clinical signs of neurological dysfunction.
      Immunohistochemical methods were used to detect Abeta and its intracellular
      precursor protein (amyloid precursor protein (APP)) and hyperphosphorylated-tau.
      APP was constitutively expressed, with diffuse staining of neurons and blood
      vessels being detected in all cats. More intense staining and diffuse
      extracellular Abeta staining deposits were found within the deep cortical areas
      of the anterior- and occasionally mid-cerebrum of seven cats, all of which were
      over 10 years of age. Neurons staining intensely positive for AT8
      immunoreactivity were seen in two cats, aged 11 and 13 years. However, no mature
      neurofibrillary tangles were detected. This study demonstrated that extracellular
      Abeta accumulation and AT8-immunoreactivity within neurons are age-related
      phenomena in cats, and that they can occur concurrently. There are similarities
      between these changes and those observed in the brains of aged people and other
      old mammals.

PMID- 16603402
TI  - Effect of sample type, and timing of assay, on feline blood potassium
      concentration.
AB  - Blood samples were collected from 41 cats presented for pre-anaesthetic
      assessments, routine geriatric screening, or re-assessment of ongoing chronic
      medical disorders. Samples were either left to clot or anticoagulated with
      lithium heparin, then assessed for their potassium concentration within 1h of
      collection, and again after remaining in contact with their cell pellet for 48 h.
      There was a significantly higher potassium concentration in the serum samples
      compared to the plasma samples, both in the basal and 48-h samples (although this
      difference was most marked in the basal samples). Ageing of both serum and plasma
      samples also resulted in an increase in the potassium concentration when compared
      with the basal values for each sample type. The mean difference (basal serum
      minus basal plasma) in potassium concentration was 0.47 mmol/l. While it is
      probable that the potassium came from either leukocytes and/or thrombocytes the
      mean total leukocyte count and the mean thrombocyte count were below the upper
      limit of the reference intervals for our laboratory and the rise in the potassium
      level did not appear to be directly related to either of these values.

PMID- 16603403
TI  - [Elective single embryo transfer: a justified policy for selected patients].
AB  - OBJECTIVE: Prevention of twin pregnancies using elective Single Embryo Transfer
      (e-SET) is now considered by many Assisted Reproductive Techniques teams as a
      necessity. The aim of this study was to assess the efficacy of e-SET in a
      prospective manner in a selective population of patients using Take Home Baby
      Rate per couple as principal parameter. PATIENTS AND METHODS: This prospective
      study was conducted from January 2003 to December 2004. Elective Single Embryo
      was proposed to women above 37 years in their first IVF or ICSI attempt. It was
      then performed only in cases when at least one embryo with high implantation
      potential (score-4 embryo in our embryo scoring) was obtained for transfer and
      one more (score-3 or score-4 embryo) was available for freezing. RESULTS: e-SET
      was proposed and accepted in 225 couples (25% of eligible couples and 7.8% of
      total population) and was possible in 96 of these). Two embryos were transferred
      in all other eligible patients (Double Embryo Transfer group=DET). Cumulative
      delivery rate after fresh embryo transfers and, if necessary, after frozen-thawed
      embryo transfers were 39.5% per couple e-SET group and 41.7% in DET group (NS).
      On the other hand, the percentage of twin pregnancies was significantly different
      between the two groups (2.6% vs 26.6% respectively; P<0.01). DISCUSSION AND
      CONCLUSION: In women younger than 37 years in their first IVF/ICSI attempt, the
      elective transfer of only one embryo with high implantation potential strongly
      allowed to avoid twin pregnancies without any significant delivery rate decrease.
      This transfer policy is particularly efficient in laboratories displaying good
      results in their embryo freezing program.

PMID- 16603404
TI  - [RCP: prevention in materno-fetal Rh immunization (CNGOF, December 2005). We
      don't have to forget to control the efficacy of these guidelines, as well as the
      prescription of the innovating technique in this field].

PMID- 16603406
TI  - Conscious, preconscious, and subliminal processing: a testable taxonomy.
AB  - Of the many brain events evoked by a visual stimulus, which are specifically
      associated with conscious perception, and which merely reflect non-conscious
      processing? Several recent neuroimaging studies have contrasted conscious and non
      conscious visual processing, but their results appear inconsistent. Some support
      a correlation of conscious perception with early occipital events, others with
      late parieto-frontal activity. Here we attempt to make sense of these dissenting
      results. On the basis of the global neuronal workspace hypothesis, we propose a
      taxonomy that distinguishes between vigilance and access to conscious report, as
      well as between subliminal, preconscious and conscious processing. We suggest
      that these distinctions map onto different neural mechanisms, and that conscious
      perception is systematically associated with surges of parieto-frontal activity
      causing top-down amplification.

PMID- 16603407
TI  - Modeling developmental cognitive neuroscience.
AB  - In the past few years connectionist models have greatly contributed to
      formulating theories of cognitive development. Some of these models follow the
      approach of developmental cognitive neuroscience in exploring interactions
      between brain development and cognitive development by integrating structural
      change into learning. We describe two classes of these models. The first focuses
      on experience-dependent structural elaboration within a brain region by adding or
      deleting units and connections during learning. The second models the gradual
      integration of different brain areas based on combinations of experience
      dependent and maturational factors. These models provide new theories of the
      mechanisms of cognitive change in various domains and they offer an integrated
      framework to study normal and abnormal development, and normal and impaired adult
      processing.

PMID- 16603408
TI  - Recent advances in the study of Clp, FtsH and other proteases located in
      chloroplasts.
AB  - Several chloroplast proteases have been characterized in recent years. The ATP
      dependent chloroplast proteases Clp and FtsH stand out because they form multi
      subunit complexes consisting of different gene products. Surprisingly, both green
      and non-green plastids appear to contain a similar soluble Clp core proteolytic
      complex, consisting of five ClpP proteases, their non-catalytic ClpR homologs,
      and two ClpS homologs that have unknown function. Analyses of single and double
      FtsH1, FtsH2, FtsH5 and FtsH8 mutants, and overexpression of FtsH proteins in
      these Arabidopsis thaliana mutants show partial redundancies within pairs of
      closely related FtsH thylakoid proteins. The presence of at least one member of
      each pair is essential for functional accumulation. Other chloroplast proteases
      have also been identified recently. Future challenges include the identification
      of substrate recognition mechanisms and elucidating the role of proteases in
      chloroplast biogenesis and function.

PMID- 16603409
TI  - An ecological and evolutionary context for integrated nitrogen metabolism and
      related signaling pathways in marine diatoms.
AB  - Whole-genome sequence analysis has revealed that diatoms contain genes and
      pathways that are novel in photosynthetic eukaryotes. More generally, the unique
      evolutionary footprint of the chromalveolates, which includes a genome fusion
      between a heterotrophic protist and a red alga in addition to a major prokaryotic
      influence, has fostered their inheritance of a unique complement of metabolic
      capabilities. Many aspects of nitrogen metabolism and cell signaling appear to be
      linked in diatoms. This new perspective provides a basis for understanding the
      ecological dominance of diatoms in contemporary oceans.

PMID- 16603410
TI  - Non-vesicular and vesicular lipid trafficking involving plastids.
AB  - In plants, newly synthesized fatty acids are either directly incorporated into
      glycerolipids in the plastid or exported and assembled into lipids at the
      endoplasmic reticulum (ER). ER-derived glycerolipids serve as building blocks for
      extraplastidic membranes. Alternatively, they can return to the plastid where
      their diacylglycerol backbone is incorporated into the glycerolipids of the
      photosynthetic membranes, the thylakoids. Thylakoid lipids are assembled at the
      plastid envelope membranes and are transferred to the thylakoids. Under phosphate
      limited growth conditions, galactolipids are exported from the outer plastid
      envelope membranes to extraplastidic membranes. Proteins, such as
      TRIGALACTOSYLDIACYLGLYCEROL1 (TGD1) or VESICLE-INDUCING PROTEIN IN PLASTIDS1
      (VIPP1), which are involved in different aspects of plastid lipid trafficking
      phenomena have recently been identified and mechanistic models that are based on
      the analysis of these components have begun to emerge.

PMID- 16603411
TI  - Chlorophyll metabolism.
AB  - Since the 1970s, researchers have proposed several regulatory pathways governing
      chlorophyll metabolism, but only recently have the underlying molecular
      mechanisms been elucidated. The recent data indicate that such regulatory systems
      are more complex than originally anticipated. For instance, the pathways involve
      a series of protein-protein interactions, including complex formation, the dual
      localization of enzymes within chloroplasts, and a novel protein degradation
      mechanism that is triggered by pigments. Furthermore, several lines of evidence
      suggest that chlorophyll metabolism might not only significantly impact the
      assembly of photosynthetic machineries but also influence processes such as
      programmed cell death, the 'stay-green' phenomenon, and chloroplast-nucleus
      communication.

PMID- 16603412
TI  - Compression of trachea due to double aortic arch: demonstration by multi-slice CT
      scan (MSCT).
AB  - Double aortic arch (DAA) is a form of vascular ring, completely encircling
      trachea and esophagus by its connecting segments, and thus can lead to clinical
      picture of aero-digestive tract obstruction. MRI and CECT in addition to the
      location and extent of aero-digestive tract obstruction can also delineate
      adjacent cardio-vascular anatomy. 3D reconstruction of aorta and airway can be
      useful tool for pre-operative planning.

PMID- 16603413
TI  - Evaluation of the myocardial performance index for early detection of
      mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis.
AB  - AIMS: Multiple sclerosis is the most common cause of neurological disability in
      young adults. Mitoxantrone is a synthetic anthracenedione, recently approved for
      the treatment of worsening multiple sclerosis, which is known to induce
      cardiotoxicity. This study was designed to evaluate the early alterations in left
      ventricular function in patients with multiple sclerosis receiving mitoxantrone,
      by the use of the myocardial performance index, a new parameter of global
      (systolic and diastolic) ventricular function. METHODS AND RESULTS: The study
      included 29 Caucasian patients with multiple sclerosis (mean age 41.8+/-9.3
      years, 12 males and 17 females) treated with mitoxantrone (mean cumulative dose
      30.8+/-18.2 mg/m(2)) who were compared with 28 healthy subjects (mean age 37.8+/
      11.8 years, 13 males and 15 females). Both groups underwent a complete two
      dimensional and Doppler echocardiography including assessment of the mitral
      inflow and left ventricular outflow patterns for estimation of the Doppler
      derived myocardial performance index. This parameter is defined as the sum of
      isovolumic contraction time and isovolumic relaxation time, divided by
      ventricular ejection time. No differences were observed in blood pressure, heart
      rate, left ventricular diameters, mass and ejection fraction in multiple
      sclerosis patients compared to the controls. The mitral flow pattern showed a
      significant decrease of E wave calculated as peak velocity (E(pv)) (63.3+/-13.4
      vs. 77.2+/-17.2, P<0.002) and time velocity integral (E(tvi)) (8.8+/-1.9 vs.
      10.3+/-2.4, P<0.02), with a significant decrease of E(pv)/A(pv) ratio and a non
      significant decrease of E(tvi)/A(tvi) ratio in the patients. In addition, E-wave
      deceleration time was significantly increased in multiple sclerosis patients
      compared to controls (178.2+/-30.2 vs. 137.9+/-14.7, P<0.0001). The mean value of
      myocardial performance index was 0.55+/-0.1 in patients compared to 0.37+/-0.06
      in the controls (P<0.0001). A significant correlation between the given
      cumulative dose of mitoxantrone and myocardial performance index (r=0.67,
      P<0.001) and E-wave deceleration time (r=0.45, P<0.001) respectively were
      demonstrated. CONCLUSION: The myocardial performance index represents a parameter
      of combined systolic and diastolic myocardial performance strongly correlated
      with the given cumulative dose of mitoxantrone. The myocardial performance index
      may be an adjunctive parameter to conventional echocardiography for detecting sub
      clinical cardiotoxicity of mitoxantrone in the clinical management of the
      multiple sclerosis patients.

PMID- 16603414
TI  - Noninvasive assessment of myocardial bridging in the left coronary artery by
      transthoracic Doppler echocardiography.
AB  - Myocardial bridging is a common congenital coronary abnormality recognized
      primarily with systolic narrowing or 'milking effect' shown by coronary
      angiography. We report the case of a 58-year-old man with signs and symptoms of
      myocardial ischemia who underwent transthoracic echocardiography and coronary
      angiography. The present case suggests the clinical role of transthoracic
      echocardiography in demonstrating characteristic coronary flow abnormalities in
      patients with muscular bridge in the region of the mid LAD.

PMID- 16603415
TI  - Reliability of language mapping with magnetic source imaging in epilepsy surgery
      candidates.
AB  - The external validity of a noninvasive language mapping protocol with
      magnetoencephalography (MEG) has been established through direct comparisons with
      invasive functional mapping techniques. This study examines the test-retest and
      interrater reliability of this protocol under realistic testing conditions in 21
      epilepsy surgery candidates. Brain activation maps were obtained in the context
      of an auditory word recognition task and represented by temporally contiguous
      dipolar activity sources. Both the duration and strength of the associated
      magnetic flux were used as measures of the magnitude of regional brain activity.
      Hemispheric asymmetry indices based on these measures showed good interrater
      reliability and intraparticipant reproducibility. Similar findings were obtained
      with respect to the location of the geometric center of receptive language
      specific cortex (Wernicke's) area in the dominant hemisphere. The results further
      support the adequacy of this MEG-based brain mapping protocol as a noninvasive
      tool for receptive language localization in epilepsy surgery candidates.

PMID- 16603416
TI  - Cloning and expression of a GST-pi gene in Mytilus galloprovincialis. Attempt to
      use the GST-pi transcript as a biomarker of pollution.
AB  - Glutathione S-transferase is involved in the detoxication of many chemical
      compounds. Northern blot analysis of mRNA GST gene from the mussel Mytilus
      galloprovincialis shows the presence of a transcript of 850 bp (GenBank accession
      no. Gi:22094808 and AF527010). The cDNA cloned sequence is constituted by an ORF
      of 621 bp encoding for a protein of 23,700 Da present in the gills and digestive
      gland of M galloprovincialis. The sequence, called Mg (M. galloprovincialis) GST
      p, is clearly related to the pi class GST. M. galloprovincialis treated with Cd
      (200 microg/L) and BaP (100 microg/L) or co-treated with Cd and BaP take up
      cadmium in the gills (16.2 +/- 4.2 and 12.6 +/- 1.2 microg Cd/g dry wt. after
      exposure to Cd and Cd + BaP, respectively) and in the digestive gland. The
      transcription of GST-pi gene, by semi-quantitative RT-PCR, shows the lowest value
      in the digestive glands of mussels exposed to BaP, whereas the treatment with
      cadmium and the co-treatment with cadmium and BaP evoke GST-pi gene expression
      higher than controls. Mussels collected from six sites along the south coast of
      Portugal show different GST-pi transcription levels, some of which are related to
      their pollutant content.

PMID- 16603417
TI  - Regulatory challenges: lessons from recent West Nile virus trials in the United
      States.
AB  - Delays in research on emerging infections could deprive the public of appropriate
      therapies. This report describes challenges encountered in implementing two
      multicenter protocols of West Nile virus (WNV) infections in the United States
      during 2003. Protocol development times, federal regulatory approvals, and local
      Institutional Review Boards (IRB) approvals were compiled. Twenty eight
      institutions participated in a natural history study and 27 in a therapeutic
      trial of WNV developed through the National Institute of Allergy and Infectious
      Disease Collaborative Antiviral Study Group (CASG). The CASG compiled protocol
      development times, federal regulatory approvals, and local IRB approvals.
      Additional information on the local IRB process was obtained by survey of the
      investigators. Because of the lengthy development and approval process, protocols
      were distributed after the start of the epidemic season, most sites were unable
      to enroll subjects at the peak of the season, and a number of sites lacked IRB
      approval at the end of the season.

PMID- 16603418
TI  - Endogenous noradrenaline affects the maturation and function of the respiratory
      network: possible implication for SIDS.
AB  - Breathing is a vital, rhythmic motor act that is required for blood oxygenation
      and oxygen delivery to the whole body. Therefore, the brainstem network
      responsible for the elaboration of the respiratory rhythm must function from the
      very first moments of extrauterine life. In this review, it is shown that the
      brainstem noradrenergic system plays a pivotal role in both the modulation and
      the maturation of the respiratory rhythm generator. Compelling evidence are
      reported demonstrating that genetically induced alterations of the noradrenergic
      system in mice affect the prenatal maturation and the perinatal function of the
      respiratory rhythm generator and have drastic consequences on postnatal survival.
      Sudden Infant Death Syndrome (SIDS), the leader cause of infant death in
      industrialised countries, may result from cardiorespiratory disorders during
      sleep. As several cases of SIDS have been observed in infants having
      noradrenergic deficits, a possible link between prenatal alteration of the
      noradrenergic system, altered maturation and function of the respiratory network
      and SIDS is suggested.

PMID- 16603419
TI  - Differential baroreceptor modulation mediated by the ventrolateral medulla.
AB  - Previous studies have shown that pharmacological stimulation of a region
      denominated caudal pressor area (CPA), located in the caudal end of the
      ventrolateral medulla, induces increases in arterial blood pressure (BP). The aim
      of this study was to compare the responses on renal sympathetic nerve activity
      (rSNA) and BP responses mediated by stimulation of CPA or rostral ventrolateral
      medulla (RVLM), in intact or sino-aortic barodenervated rats. Male Wistar rats
      (300-350 g, n=15) were anesthetized (urethane 1.2 to 1.4 g/kg, i.v.) and
      artificially ventilated. The mean arterial pressure (MAP) and rSNA were measured
      during bilateral glutamate microinjection (10 nmo/100 nl) into the CPA or into
      the RVLM. Glutamatergic stimulation of the RVLM increased MAP (46+/-7 mm Hg) and
      rSNA (82+/-21%); during CPA stimulation, MAP and rSNA increased 60+/-7 mm Hg and
      93+/-9%, respectively. However, despite the similarity of responses mediated by
      both regions, the duration of rSNA and blood pressure responses mediated by the
      CPA were significantly longer than the duration of the responses mediated by the
      RVLM. After barodenervation, there was an increase in the time-course and
      magnitude of sympathetic response only in response to RVLM stimulation but not in
      response to CPA. The results suggest a differential baroreceptor modulation on
      rSNA mediated by the ventrolateral medulla neurons. Glutamatergic activation of
      CPA neurons can cause large increases in the rSNA and BP with a weaker
      baroreceptor modulation when compared to responses mediated by the RVLM neurons.

PMID- 16603420
TI  - Involvement of the medial prefrontal cortex in central cardiovascular modulation
      in the rat.
AB  - The medial prefrontal cortex (MPFC) and specifically its ventral portion (vMPFC)
      have been reported to modulate autonomic responses. On the cardiovascular system,
      this modulation is characterized by an influence on arterial blood pressure,
      regional blood flow as well as cardiac sympathetic and parasympathetic responses.
      The vMPFC also modulates baroreflex activity. Several neurotransmitters are
      present in the vMPFC. Among them L-glutamate, acetylcholine and noradrenaline are
      involved with cardiovascular modulation. In the present review, we describe
      evidences on the mechanisms involved in the vMPFC-related cardiovascular
      modulation.

PMID- 16603421
TI  - Fecal elastase-1: utility in pancreatic function in cystic fibrosis.
AB  - Early detection and management of pancreatic insufficiency is essential to
      optimize health and outcomes in cystic fibrosis patients. The gold standard
      measures for assessment of pancreatic function are direct pancreatic stimulation
      tests, which have numerous limitations. Estimation of fecal elastase-1 level to
      determine pancreatic function is an attractive alternative as the test is simple,
      rapid, cost-effective and easy to perform even in children. This review
      summarizes the data from studies reflecting the validity, limitation and
      advantages of fecal elastase-1 in assessing pancreatic function in cystic
      fibrosis patients.

PMID- 16603422
TI  - Quantification of lysophosphatidylcholines and phosphatidylcholines using liquid
      chromatography-tandem mass spectrometry in neonatal serum.
AB  - We established an improved method for quantification of phosphatidylcholine (PC)
      and lysophosphatidylcholine (LPC) molecular species in neonatal serum using high
      performance liquid chromatography coupled tandem mass spectrometry (LC-MS/MS). A
      multiple reaction monitoring (MRM) mode of positive ionization for MS/MS was
      used. The method involved purification of phospholipids by solid phase extraction
      (SPE) from a 20-microl minimum specimen of serum. The assayed values of authentic
      16:0-LPC and 18:0-LPC showed a linear response, and our quantitative results
      showed high precision for the all species of PC and LPC. Then, we quantified PC
      and LPC in adult and neonatal serum and compared them. Day 0-1 neonatal serum
      16:0-, 18:0-, 18:1-, 18:2-LPC levels were significantly lower than adult ones.
      All species LPC levels in the day 0-1 neonates were significantly lower than day
      4-8 neonates. Day 0-1 neonatal serum 16:0/18:2-, 18:0/18:2-PC levels were
      significantly lower than adult ones. Our method is advantageous for precise
      assessments of the relationships between PCs/LPCs levels and neonatal infectious
      diseases.

PMID- 16603423
TI  - C-terminal residues of plant glutamate decarboxylase are required for
      oligomerization of a high-molecular weight complex and for activation by
      calcium/calmodulin.
AB  - Bacterial glutamate decarboxylase (GAD) is a homohexameric enzyme of about 330
      kDa. Plant GAD differs from the bacterial enzyme in having a C-terminal extension
      of 33 amino acids within which resides a calmodulin (CaM)-binding domain. In
      order to assess the role of the C-terminal extension in the formation of GAD
      complexes and in activation by Ca2+/CaM, we examined complexes formed with the
      purified full-length recombinant petunia GAD expressed in E. coli, and with a 9
      amino acid C-terminal deletion mutant (GADDeltaC9). Size exclusion chromatography
      revealed that the full-length GAD formed complexes of about 580 kDa and 300 kDa
      in the absence of Ca2+/CaM, whereas in the presence of Ca2+/CaM all complexes
      shifted to approximately 680 kDa. With deletion of 9 amino acids from the C
      terminus (KKKKTNRVC(500)), the ability to bind CaM in the presence of Ca2+, and
      to purify it by CaM-affinity chromatography was retained, but the formation of
      GAD complexes larger than 340 kDa and enzyme activation by Ca2+/CaM were
      completely abolished. Hence, responsiveness to Ca2+/CaM is associated with the
      formation of protein complexes of 680 kDa, and requires some or all of the nine C
      terminal amino acid residues. We suggest that evolution of plant GAD from a
      bacterial ancestral enzyme involved the formation of higher molecular weight
      complexes required for activation by Ca2+/CaM.

PMID- 16603424
TI  - Structural cooperativity in spectrin type repeats motifs of dystrophin.
AB  - Dystrophin is a member of the spectrin family of proteins, which are
      characterized as being predominantly composed the spectrin-type-repeat, a triple
      alpha-helical bundle motif present in multiple tandem copies, producing a rod
      like shape. Whether or not this motif, which is determined by sequence homology,
      is correlated with biophysical domains in the intact protein is uncertain. The
      nature of the domain structure impacts the flexibility and shape of the rod
      region of this protein, which is a target for modification in several therapeutic
      approaches aimed at Duchenne Muscular Dystrophy, a common and fatal genetic
      disease caused by defective dystrophin. We examined three such motifs in
      dystrophin, expressing them recombinantly both singly and in tandem, and studying
      their thermodynamic properties by solvent and thermal denaturation. We have found
      that the degree to which they are independently stable and expressible varies
      considerably. The fourth motif appears to be largely stable and independent,
      whereas the third and second motifs interact strongly.

PMID- 16603425
TI  - Early recognition of neonatal hyperbilirubinemia and its emergent management.
AB  - Hyperbilirubinemia and kernicterus are re-emerging as prominent clinical concerns
      and have been hypothesized to be secondary to increased breast-feeding rates,
      early hospital discharges and overall lack of concern for the potential impact of
      severe hyperbilirubinemia on healthy term newborns. Although the clinical
      symptoms can be non-specific and vague, they could be early, insidious and
      heralding signs of acute bilirubin encephalopathy (ABE) or acute stage
      kernicterus. Because it is highly prevalent, evaluation of a jaundiced neonate
      requires detailed questions about specific signs, review of birth and postnatal
      histories, evaluation of predischarge data, and possibly an emergency clinical
      evaluation of the neurological status of the infant. Medical urgency to evaluate,
      investigate and monitor such a newborn ensues from the possibility of rapid
      progression that might lead to permanent sequelae of bilirubin-induced neurologic
      dysfunction (BIND). Early recognition of the urgency and rapid transition to
      treatment seem to be the major barriers leading to delay in therapy. However,
      because there is a well-established and relatively safe treatment for neonatal
      jaundice, there should be zero tolerance for kernicterus, and BIND prevention has
      become a national priority in the USA. This paper reviews the clinical signs and
      epidemiology of ABE and BIND and presents a system-based strategy for preventing
      their occurrence, focusing particularly on the transition from recognition of
      clinical jaundice to actual treatment. A novel emergency-room-based protocol is
      presented as an example of how to expedite and facilitate rapid progression to
      treatment.

PMID- 16603426
TI  - (Epi)mutations in 11p15 significantly contribute to Silver-Russell syndrome: but
      are they generally involved in growth retardation?
AB  - (Epi)mutations affecting chromosome 11p15 are meanwhile well known to be
      associated with growth disturbances. The finding of 11p15 mutations in the
      overgrowth disease Beckwith-Wiedemann syndrome (BWS) led to the identification of
      imprinted growth-promoting genes which are expressed paternally and of imprinted
      growth-suppressing genes in the same region that are expressed maternally.
      Recently, the opposite (epi)mutations of the same region have been reported to
      result in growth retardation: maternal duplications of 11p15 as well as
      hypomethylation of the telomeric 11p15 imprinting domain (ICR1) could be
      identified in patients with Silver-Russell syndrome (SRS), a disease which is in
      particular characterised by intrauterine and postnatal growth retardation. To
      elucidate whether 11p15 mutations are generally involved in growth retardation we
      screened 125 growth retarded patients, among them 47 patients with SRS-like
      features and 20 with isolated growth retardation. Additional 58 patients were
      presented with clinical signs not consistent with SRS. We excluded 11p15
      duplications in all 123 families by short tandem repeat typing. ICR1
      hypomethylation was investigated by Southern-blot analyses and was therefore
      restricted to samples with a large amount of DNA. We identified ICR1
      hypomethylation in 20% of the patients with SRS-like features (n=25). No further
      cases were detectable in the other two subgroups with isolated growth retardation
      (n=20) and with clinical signs not consistent with SRS (n=23), respectively. Our
      data show that 11p15 duplications are rare in growth retardation in general and
      that they seem to be restricted to patients with SRS features. Furthermore,
      testing for the ICR1 hypomethylation should also be focused on patients with SRS
      features. While the ICR1 epimutation is detectable with a significant frequency
      only in SRS patients, its role for isolated growth retardation remains to be
      elucidated.

PMID- 16603427
TI  - Increased incidence of hip fractures. A population based-study in Finland.
AB  - In Central Finland, the age-specific incidence of hip fractures did not change
      between the years 1982-1983 and 1992-1993 though the total number of hip
      fractures increased by 11% due to population aging. The objective of this study
      was to define the current hip fracture rates and the characteristics of patients
      with hip fracture. The population at risk consisted of 240,000 persons living in
      the Central Finland Health Care District. Hip fracture patients were identified
      by using the hospital discharge register, the operation lists, and the register
      of the Department of Anesthesiology. Patients' residential status, weight, and
      height, date and time of hip fracture, place of accident and mechanism and type
      of fracture were obtained from medical records. A total of 597 patients, 415
      (69.5%) women and 182 (30.5%) men, were admitted to the hospital for treatment of
      an acute hip fracture in 2002-2003. The mean age of the patients was 79 (SD 13)
      years. Among patients aged > or =50 years (n = 577), 80.8% of the hip fractures
      had occurred indoors, 97.6% with a low-energetic mechanism, and 22.7% during the
      nighttime. The ratio of trochanteric to cervical fractures was 2:3. Between 1992
      1993 and 2002-2003, the total number of hip fractures increased by 70%, from 351
      to 597. The fracture rates per 1000 person-years in the age group > or =55 years
      were 2.0 and 3.9 in 1992-1993 and 2.8 and 5.6 in 2002-2003 for men and women,
      respectively. The corresponding age-adjusted incidence rate ratio (IRR) for men
      was 1.36 (95% CI: 1.06 to 1.76), P = 0.017, and for women 1.25 (95% CI: 1.07 to
      1.47), P = 0.006. Among men, the IRR was highest in the age group 75-84 years,
      IRR = 1.67 (95% CI: 1.08 to 2.65), while among women, it was highest in the age
      group > or =85 years, IRR = 1.33 (95% CI: 1.02 to 1.75). The total number of hip
      fractures almost doubled within 10 years, and the age-adjusted incidence rate
      increased in both sexes. The accretion of the hip fracture incidence was more
      than could be explained merely by changes in population size and structure.

PMID- 16603428
TI  - Effect of gonadotropin-releasing hormone agonist and antagonist on
      steroidogenesis of low responders undergoing in vitro fertilization.
AB  - The aim of the study was to investigate the cause of the lower estradiol (E(2))
      concentration in women treated with gonadotropin-releasing hormone (GnRH)
      antagonist compared with those treated with agonist protocol in in vitro
      fertilization (IVF). Thirty patients who were known low responders were
      prospectively randomized into two equal groups for IVF treatment. Group 1 used
      GnRH agonist (flare-up) protocol and group 2 used antagonist protocol. The
      results showed that serum luteinizing hormone (LH) levels were significantly
      higher in the agonist group during the folliculogenesis stage. Despite this
      higher LH, serum E(2) levels were significantly higher in the agonist group on
      cycle day 2 only, not on day 5 or day 9. The significantly higher E(2) level in
      the agonist group reappeared on the day of administration of human chorionic
      gonadotropin (hCG). The rate of folliculogenesis in the antagonist group was
      faster than in the agonist group; therefore their E(2) production should have
      been higher on hCG day. Furthermore, the rate of decline in E(2) after hCG
      administration was significantly higher in the antagonist group. These findings,
      along with the fact that both groups received exogenous LH (human menopausal
      gonadotropin) that should optimize steroidogenesis and make the difference in
      E(2) insignificant, enable us to conclude that GnRH antagonists have a
      suppressive effect on the production of E(2).

PMID- 16603429
TI  - Neuroprotective effects of soy phytoestrogens in the rat brain.
AB  - Soy extracts are widely used as an alternative to hormone replacement therapy for
      the treatment of menopausal symptoms. Soy phytoestrogens, such as genistein, may
      act on the nervous system, affecting mood, cognitive function and behavior. In
      addition, several studies suggest that soy phytoestrogens are neuroprotective.
      The hypothesis of the present study was that soy extracts may exert
      neuroprotection and that this effect is mediated by phytoestrogens such as
      genistein. To test this hypothesis we assessed whether an acute administration of
      soy extract or genistein in vivo affects hippocampal neuronal loss induced by the
      systemic administration of kainic acid to adult Wistar female rats. One week
      after ovariectomy, animals received one intraperitoneal injection of soy extract
      (0.2, 1, 2 or 20 mg/kg), one injection of genistein (0.1, 1 or 10 mg/kg) or one
      injection of vehicle. Thirty minutes later, all animals received one
      intraperitoneal injection of kainic acid (7 mg/kg) or vehicle. One week after the
      injections, all animals were fixed by perfusion and the number of Nissl-stained
      neurons in the hilus of the dentate gyrus was estimated by the optical disector
      method. Administration of soy extract, even at high doses, did not induce
      neuronal loss and did not increase neuronal degeneration after kainic acid
      injury. On the contrary, soy extract at doses ranging from 1 to 20 mg/kg
      prevented neuronal loss induced by kainic acid. Genistein showed neuroprotective
      effects only at high dose (10 mg/kg), suggesting that other components in the soy
      extract are involved in the neuroprotective effect.

PMID- 16603430
TI  - A pilot study on the effects of a Chinese herbal preparation on menopausal
      symptoms.
AB  - This study was conducted to determine whether a particular Chinese medicinal
      preparation is effective in alleviating menopausal symptoms. Chinese women with
      menopausal symptoms were recruited to receive treatment for 3 months followed by
      3 months without treatment. The severity of menopausal symptoms and serum
      follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol levels
      were assessed at baseline, 3 and 6 months. Data from 97 women with a mean age of
      52.3 years were analyzed. Sixty women (62%) were postmenopausal. The serum FSH
      level (interquartile range) was 58.0 (39.5-72.4) IU/l at baseline and rose
      significantly 3 months after treatment. The difference remained significant in
      the postmenopausal group while there was no significant difference in the
      perimenopausal women. The changes in serum LH and estradiol levels remained
      unchanged. The baseline menopausal symptom score was 8.9 +/- 6.0. The menopausal
      symptom score improved markedly after treatment and remained at the same level at
      6 months. All individual menopausal symptoms improved significantly after 3
      months of treatment except dry eye. Most of these symptoms remained significantly
      improved at 6 months compared with the pre-treatment assessment. We observed that
      the Chinese medicinal preparation used in this study is effective in improving
      menopausal symptoms in healthy Chinese women. Further randomized controlled trial
      will be needed to confirm this observation.

PMID- 16603432
TI  - Health-related quality of life in women with polycystic ovary syndrome: a
      comparison with the general population using the Polycystic Ovary Syndrome
      Questionnaire (PCOSQ) and the Short Form-36 (SF-36).
AB  - BACKGROUND: We examined whether women with polycystic ovary syndrome (PCOS) have
      poorer health-related quality of life (HRQoL) than women in the general
      population and than patients with other medical conditions. METHOD: Women with
      PCOS were recruited from an outpatient clinic and a control group was recruited
      from a family planning clinic. Both groups completed the Short Form-36 (SF-36)
      and the Polycystic Ovary Syndrome Questionnaire (PCOSQ). SF-36 data from the
      Oxford Health and Lifestyle Survey were used to compare PCOS with other
      conditions. RESULTS: Twenty-two women with PCOS and 96 control women took part.
      Women with PCOS scored lower in both summary scores of the SF-36 and in all
      domains of the PCOSQ. After adjusting for body mass index, the differences
      between the groups in the SF-36 disappeared, while those in the PCOSQ remained.
      When compared with asthma, epilepsy, diabetes, back pain, arthritis and coronary
      heart disease, our PCOS group had the same or better physical HRQoL but poorer
      psychological HRQoL. The PCOSQ showed good internal reliability, good concurrent
      validity and good discriminant validity. CONCLUSIONS: PCOS has a negative impact
      on HRQoL even when compared with other serious health conditions. The PCOSQ is
      reliable and valid for clinical use.

PMID- 16603431
TI  - Ovariectomy exacerbates oxidative stress and cardiopathy induced by adriamycin.
AB  - Ovarian hormone depletion in ovariectomized experimental animals is a useful
      model with which to study the physiopathological consequences of menopause in
      women. It has been suggested that menopause is a risk factor for the induction of
      several cardiovascular disorders. In the present study we analyzed the effects of
      ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and
      cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured
      parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase,
      aspartate aminotransferase and alanine aminotransferase) and oxidative stress
      (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced
      glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and
      erythrocytes. OVX was found to alter all markers of oxidative stress and cell
      damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones
      enhanced cardiac damage and oxidative stress induced by AD. Our results suggest
      that antioxidant status in cardiac tissue and erythrocytes is seriously
      compromised by OVX during the cardiomyopathy induced by AD in experimental
      animals. In conclusion, the absence of hormones caused by OVX or menopause may
      induce or accelerate pre-existing cardiovascular dysfunctions.

PMID- 16603433
TI  - The CYP17 MspA1 polymorphism is not associated with an increased risk of uterine
      leiomyomas in a Japanese population.
AB  - The CYP17 gene is thought to be a candidate gene for susceptibility to hormone
      related diseases. A single (T?C) nucleotide polymorphism in the promoter region
      of CYP17 is speculated to influence its transcription. The present study was
      conducted to investigate the possible association between uterine leiomyomas and
      CYP17 gene polymorphism in a Japanese population. Genotyping analysis of the
      CYP17 gene was performed in 138 leiomyoma cases, 183 unaffected controls and 179
      population controls using polymerase chain reaction and restriction fragment
      length polymorphism analysis. No significant difference in CYP17 genotype
      distribution was noted between leiomyoma cases and controls. Women carrying the
      A2 allele were not at an increased risk of uterine leiomyoma compared with those
      carrying the A1 allele in unaffected controls (odds ratio, 1.26; 95% confidence
      interval, 0.92-1.72) and those carrying the A1 allele in population controls
      (odds ratio, 0.99; 95% confidence interval, 0.72-1.36). No significant difference
      in allele frequencies were found between leiomyoma cases and controls. These
      findings suggest that CYP17 gene polymorphism is unlikely to be associated with
      an increased risk of uterine leiomyomas in a Japanese population.

PMID- 16603435
TI  - Cyclooxygenase-2 expression in the endometrium and its relationship to bleeding
      in users of continuous oral contraceptives.
AB  - OBJECTIVE: The objective of the present study was to investigate whether or not
      the presence of irregular bleeding during use of oral contraceptives (OC) is
      associated with increased cyclooxygenase-2 (COX-2) expression. PATIENTS AND
      METHODS: An observational study was carried out in 26 patients who were using
      gestodene 75 microg/ethinylestradiol 30 microg prior to endometrial resection.
      The patients were divided into two groups: those with amenorrhea (n = 14) and
      those who had irregular bleeding (n = 12). The resected endometrium was
      immunostained for COX-2, Bcl-2 and Ki-67 expression. Routine pathology was
      carried out using standard hematoxylin-eosin staining. RESULTS: Irregular
      bleeding during OC use was associated with strong COX-2 expression in both
      glandular and superficial epithelium. There were also more patients in this group
      with irregular endometrial maturation and higher Ki-67 values. Bcl-2 expression,
      on the other hand, was not affected by the presence of uterine bleeding.
      CONCLUSION: The presence of irregular bleeding during OC use is associated with
      strong COX-2 expression in the endometrium, thereby suggesting a pivotal role of
      prostaglandins in this process.

PMID- 16603436
TI  - Prevalence and clinical predictors of endometrial hyperplasiain anovulatory women
      presenting with amenorrhea.
AB  - The aim of the present study was to determine the prevalence and clinical
      predictors of endometrial hyperplasia (EH) in amenorrheic women with anovulation.
      Fifty-seven women were enrolled in the study. Of these, 43 were diagnosed to have
      polycystic ovary syndrome (PCOS) and 14 to have idiopathic anovulation. All women
      received transvaginal sonography to assess endometrial thickness (ET), patterns
      and abnormalities. At the same time, an endometrial biopsy was taken using a
      Pipelle instrument. The women's age, body mass index (BMI) and waist-to-hip ratio
      (WHR) were 32.0+/-6.0 years, 27.3+/-6.5 kg/m(2) and 0.82+/-0.06 (mean+/-standard
      deviation), respectively. Twenty (35.1%) and 19 (33.3%) women were classified as
      obese by BMI and WHR, respectively. Hypertension was found in 17 (29.8%) women.
      The prevalence of EH was 45.6%. Most cases were simple EH, and only one (1.75%)
      was simple EH with atypia. EH prevalence was 48.8% and 35.7% in PCOS and
      idiopathic anovulatory women, respectively. Age, BMI, WHR and ET did not predict
      EH, whereas the endometrial hyperechogenic pattern was a clinical predictor of EH
      with borderline significance. In conclusion, this study demonstrated that almost
      half of the anovulatory women with amenorrhea had EH and no significant predictor
      was found. In view of these findings, an endometrial biopsy should be performed
      in all women with this disorder.

PMID- 16603434
TI  - Low serum concentrations of di-(2-ethylhexyl)phthalate in women with uterine
      fibromatosis.
AB  - Di-(2-ethylhexyl)phthalate (DEHP) is the most commonly used plasticizer in
      flexible polyvinylchloride formulations, and is a widespread ubiquitous
      environmental contaminant. A potential role of exposure to DEHP and its primary
      metabolite, monoethylhexylphthalate (MEHP), on women's reproductive function is
      suggested in the current study. The aim of the study was to test serum
      concentrations of DEHP and/or MEHP in women with uterine fibromatosis. Two groups
      of women were enrolled in the study: (i) women with uterine fibromatosis
      undergoing surgical menopause (n = 15) and (ii) healthy women (n = 20). Serum
      DEHP and MEHP concentrations were measured by high-performance liquid
      chromatography. Serum MEHP distribution was found to be non-Gaussian (p = 0.001)
      while serum DEHP distribution was compatible with a normal curve (p = 0.141).
      Patients with uterine fibromatosis showed significantly lower serum MEHP
      concentrations (median [interquartile range]: 0 [0-0] microg/ml, range: 0-0.57
      microg/ml) than controls (0.42 [0-0.51] microg/ml, range: 0-1.20 microg/ml, z = 
      2.93, p = 0.0034). Likewise, serum DEHP concentrations in women with fibromatosis
      were found to be significantly lower than in controls (patients: 0.27 +/- 0.096
      microg/ml (mean +/- standard deviation (SD)), range: 0.14-0.59 microg/ml vs.
      controls: 0.30 +/- 0.14 microg/ml (mean +/- SD), range: 0-0.63 microg/ml; t =
      3.212, df = 33, difference: -0.325 (95% confidence interval: -0.5309, -0.1191), p
      = 0.0029). In conclusion, the present findings indicate for the first time that
      serum DEHP and MEHP concentration are lower in women with uterine fibromatosis,
      suggesting a possible correlation between phthalate esters and fibromatosis
      pathology.

PMID- 16603437
TI  - Effects of the position of fibroids on fertility.
AB  - This prospective, controlled study was performed in order to evaluate whether the
      location of uterine fibroids may influence reproductive function in women and
      whether removal of the fibroid prior to conception may improve pregnancy rate and
      pregnancy maintenance. We examined 181 women affected by uterine fibroids who had
      been trying to conceive for at least 1 year without success. The main outcome
      measures were the pregnancy rate and the miscarriage rate. Among the patients who
      underwent myomectomy, the pregnancy rates obtained were 43.3% in cases of
      submucosal, 56.5% in cases of intramural, 40.0% in cases of submucosal-intramural
      and 35.5% in cases of intramural-subserosal uterine fibroids, respectively. Among
      the patients who did not undergo surgical treatment, the pregnancy rates obtained
      were 27.2% in women with submucosal, 41.0% in women with intramural, 15.0% in
      women with submucosal-intramural and 21.43% in women with intramural-subserosal
      uterine fibroids, respectively. Although the results were not statistically
      significant in the group of women with intramural and intramural-subserosal
      fibroids, this study confirms the important role of the position of the uterine
      fibroid in infertility as well as the importance of fibroids removal before the
      achievement of a pregnancy, to improve both the chances of fertilization and
      pregnancy maintenance.

PMID- 16603439
TI  - Antibodies against beta2-glycoprotein I complexed with an oxidised lipoprotein
      relate to intima thickening of carotid arteries in primary antiphospholipid
      syndrome.
AB  - To explore whether antibodies against beta2-glycoprotein I (beta2GPI) complexed
      to 7-ketocholesteryl-9-carboxynonanoate (oxLig-1) and to oxidised low-density
      lipoproteins (oxLDL) relate to paraoxonase activity (PONa) and/or intima media
      thickness (IMT) of carotid arteries in primary antiphospholipid syndrome (PAPS).
      As many as 29 thrombotic patients with PAPS, 10 subjects with idiopathic
      antiphospholipid antibodies (aPL) without thrombosis, 17 thrombotic patients with
      inherited thrombophilia and 23 healthy controls were investigated. The following
      were measured in all participants: beta2GPI-oxLDL complexes, IgG anti-beta2GPI
      oxLig-1, IgG anti-beta2GPI-oxLDL antibodies (ELISA), PONa, (para-nitrophenol
      method), IMT of common carotid (CC) artery, carotid bifurcation (B), internal
      carotid (IC) by high resolution sonography. Beta2GPI-oxLDL complex was highest in
      the control group (p < 0.01), whereas, IgG anti-beta2GPI-oxLig1 and IgG anti
      beta2GPI-oxLDL were highest in PAPS (p < 0.0001). In healthy controls, beta2GPI
      oxLDL complexes positively correlated to IMT of the IC (p = 0.007) and negatively
      to PONa after correction for age (p < 0.03). PONa inversely correlated with age
      (p = 0.008). In PAPS, IgG anti-beta2GPI-oxLig-1 independently predicted PONa (p =
      0.02) and IMT of B (p = 0.003), CC, (p = 0.03) and of IC (p = 0.04). In PAPS,
      PONa inversely correlated to the IMT of B, CC and IC (p = 0.01, 0.02 and 0.003,
      respectively). IgG anti-beta2GPI-oxLig-1 may be involved in PAPS related
      atherogenesis via decreased PON activity.

PMID- 16603438
TI  - Ovarian hyperstimulation caused by gonadotroph cell adenoma: a case report and
      review of the literature.
AB  - OBJECTIVE: We present a case of spontaneous ovarian hyperstimulation caused by
      pituitary gonadotroph macroadenoma, and include a review of the literature. CASE
      REPORT: A 27-year-old woman presented with irregular menstruation and bilateral
      multicystic enlargement of the ovaries. Serum estradiol (E(2)) levels were
      marginally elevated for the follicular phase but within the physiological range.
      Serum luteinizing hormone (LH) was extremely low, follicle-stimulating hormone
      (FSH) was normal, and prolactin (PRL) was high. Magnetic resonance imaging
      disclosed a pituitary macroadenoma. Immunohistochemical examination of the
      surgically removed adenoma showed intense reactivity for FSH and LH. After the
      operation, E(2), LH and PRL levels were normalized, the ovaries returned to a
      normal morphology, and regular menstrual cycles were resumed. CONCLUSION: A
      review of the literature showed that ovarian hyperstimulation caused by pituitary
      gonadotroph adenoma is not always accompanied by elevated FSH levels. High PRL
      and E(2) and low LH were reported in the majority of the cases, but E(2) may stay
      within the range observed in normal menstrual cycles.

PMID- 16603440
TI  - Serum islet cell autoantibodies during interferon alpha treatment in patients
      with HCV-genotype 4 chronic hepatitis.
AB  - Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver
      disease worldwide and HCV genotype 4 (HCV4) is predominant in African and Middle
      Eastern countries. It is well established that interferon-a (IFNa) treatment for
      HCV may trigger serum autoantibodies against pancreatic islet cells (ICA) in a
      subgroup of patients. Available data on the incidence of ICA during IFNa therapy
      for chronic HCV4 infection are not conclusive. We investigated the appearance of
      ICA in 40 naive Egyptian patients (38 males, 32 +/- 6 years) with histologically
      defined chronic HCV4 infection undergoing IFNa treatment at a dose of 9-million
      U/week for 24 weeks. Serum samples were collected at baseline and following IFNa
      therapy and ICA were detected using indirect immunofluorescence. Baseline
      evaluation indicated that 2/40 (5%) patients had detectable serum ICA. After the
      completion of the treatment scheme, 12/38 (32%) previously ICA negative patients
      became ICA positive; however, no patient developed impaired glucose tolerance
      (IGT) or diabetes during follow-up. In conclusion, we submit that IFNa treatment
      for chronic hepatitis C (CHC) may induce serum ICA in one-third of Egyptian
      patients with HCV4. These autoantibodies, however, do not lead to alterations in
      glucose metabolism.

PMID- 16603441
TI  - Reduced incidence of slowly progressive Heymann nephritis in rats immunized with
      a modified vaccination technique.
AB  - A slowly progressive Heymann nephritis (SPHN) was induced in three groups of rats
      by weekly injections of a chemically modified renal tubular antigen in an aqueous
      medium. A control group of rats received the chemically unmodified version of the
      antigen in an aqueous solution. One group of SPHN rats were pre- and post-treated
      with weekly injections of IC made up of rKF3 and rarKF3 IgM antibody at antigen
      excess (MIC) (immune complexes [ICs] containing sonicated ultracentrifuged [u/c]
      rat kidney fraction 3 [rKF3] antigen and IgM antibodies specific against the
      antigen, at slight antigen excess). One group of SPHN rats were post-treated with
      MIC 3 weeks after the induction of the disease and one group of SPHN animals
      received no treatment. The control group of rats received pre- and post-treatment
      with sonicated u/c rKF3. The incidence of immune-complex glomerulonephritis
      (ICGN) in the untreated SPHN rats was 87%, in the pre- and post-treated animals
      13%, and in the post-treated-only rats 20%. Rats receiving sonicated
      ultracentrifuged rKF3 antigen did not develop ICGN. The present experiment
      demonstrates that the development of SPHN can be not only prevented but also
      effectively terminated by our newly developed modified vaccination technique.

PMID- 16603442
TI  - Postulated vasoactive neuropeptide autoimmunity in fatigue-related conditions: a
      brief review and hypothesis.
AB  - Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are
      characterised by prolonged fatigue and a range of debilitating symptoms of pain,
      intellectual and emotional impairment, chemical sensitivities and immunological
      dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain
      features in common with these conditions. Post-infection sequelae may be possible
      contributing factors although ongoing infection is unproven. Immunological
      aberration may prove to be associated with certain vasoactive neuropeptides (VN)
      in the context of molecular mimicry, inappropriate immunological memory and
      autoimmunity. Adenylate cyclase-activating VNs including pituitary adenylate
      cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and
      calcitonin gene-related peptide (CGRP) act as hormones, neurotransmitters,
      neuroregulators, immune modulators and neurotrophic substances. They and their
      receptors are potentially immunogenic. VNs are widely distributed in the body
      particularly in the central and peripheral nervous systems and have been
      identified in the gut, adrenal gland, blood cells, reproductive system, lung,
      heart and other tissues. They have a vital role in maintaining cardio-respiratory
      function, thermoregulation, memory, concentration and executive functions such as
      emotional responses including social cues and appropriate behaviour. They are co
      transmitters for a number of neurotransmitters including acetylcholine and
      gaseous transmitters, are potent immune regulators with primarily anti
      inflammatory activity, and have a significant role in protection of the nervous
      system against toxic assault as well as being important in the maintenance of
      homeostasis. This paper describes a biologically plausible mechanism for the
      development of certain fatigue-related syndromes based on loss of immunological
      tolerance to these VNs or their receptors following infection, other events or de
      novo resulting in significant pathophysiology possibly mediated via CpG fragments
      and heat shock (stress) proteins. These conditions extend the public health
      context of autoimmunity and VN dysregulation and have implications for military
      medicine where radiological, biological and chemical agents may have a role in
      pathogenesis. Possible treatment and prevention options are considered.

PMID- 16603443
TI  - Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract
      infection.
AB  - Rheumatoid arthritis (RA) is a chronic and disabling polyarthritic disease, which
      affects mainly women in middle and old age. Extensive evidence based on the
      results of various microbial, immunological and molecular studies from different
      parts of the world, shows that a strong link exists between Proteus mirabilis
      microbes and RA. We propose that sub-clinical Proteus urinary tract infections
      are the main triggering factors and that the presence of molecular mimicry and
      cross-reactivity between these bacteria and RA-targeted tissue antigens assists
      in the perpetuation of the disease process through production of cytopathic auto
      antibodies. Patients with RA especially during the early stages of the disease
      could benefit from Proteus anti-bacterial measures involving the use of
      antibiotics, vegetarian diets and high intake of water and fruit juices such as
      cranberry juice in addition to the currently employed treatments.

PMID- 16603444
TI  - Antigenic complementarity in the origins of autoimmunity: a general theory
      illustrated with a case study of idiopathic thrombocytopenia purpura.
AB  - We describe a novel, testable theory of autoimmunity, outline novel predictions
      made by the theory, and illustrate its application to unravelling the possible
      causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically
      complementary antigens induce complementary immune responses (antibody or T-cell)
      that create loss of regulation and civil war within the immune system itself.
      Antibodies attack antibodies creating circulating immune complexes; T-cells
      attack T-cells creating perivascular cuffing. This immunological civil war
      abrogates the self-nonself distinction. If at least one of the complementary
      antigens mimics a self antigen, then this unregulated immune response will target
      host tissues as well. Data demonstrating that complementary antigens are found in
      some animal models of autoimmunity and may be present in various human diseases,
      especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or
      suppressing existing autoimmunity are derived from the theory, and critical tests
      proposed. Finally, we argue that Koch's postulates are inadequate for
      establishing disease causation for multiple-antigen diseases and discuss the
      possibility that current research has failed to elucidate the causes of human
      autoimmune diseases because we are using the wrong criteria.

PMID- 16603446
TI  - Reduced hematopoietic toxicity, enhanced cellular uptake and altered
      pharmacokinetics of azidothymidine loaded galactosylated liposomes.
AB  - In order to target liposomes to the lectin receptors present on macrophages,
      galactosylated liposomes were prepared and characterized in vitro. O
      palmitoylgalactose (OPG) for liposomal coating was synthesized by esterification
      of galactose with palmitoyl chloride. The galactose binding Ricinus communis
      lectin was employed as a model system for the determination of in vitro ligand
      binding capacity. Cellular drug uptake studies were performed using alveolar
      macrophages. Hematological changes, bone marrow toxicity, plasma and tissue
      distribution study of free, uncoated plain liposomal and galactosylated liposomal
      encapsulated azidothymidine (AZT) were determined following a bolus intravenous
      injection in Sprague-Dawley rats. Lectin (R. communis) carbohydrate interaction
      has been utilized for the effective delivery of AZT entrapped in galactosylated
      vesicles. Aggregation of galactosylated liposomes increased as lectin
      concentration was increased from 5 to 30 microg/ml. Cellular uptake of
      galactosylated liposomal formulation was maximum. No hematological toxicity was
      observed even after 10 days in case of galactosylated vesicle entrapped AZT. This
      formulation maintained a significant level of AZT in tissues rich in galactose
      specific receptors and had a prolonged residence in the body resulting in
      enhanced half-life of AZT. Conclusively, galactosylated liposomes are the
      potential candidate for targeted drug delivery and are anticipated to be
      promising in the treatment of AIDS6.

PMID- 16603445
TI  - Cure of chronic viral infection and virus-induced type 1 diabetes by neutralizing
      antibodies.
AB  - The use of neutralizing antibodies is one of the most successful methods to
      interfere with receptor-ligand interactions in vivo. In particular blockade of
      soluble inflammatory mediators or their corresponding cellular receptors was
      proven an effective way to regulate inflammation and/or prevent its negative
      consequences. However, one problem that comes along with an effective
      neutralization of inflammatory mediators is the general systemic immunomodulatory
      effect. It is, therefore, important to design a treatment regimen in a way to
      strike at the right place and at the right time in order to achieve maximal
      effects with minimal duration of immunosuppression or hyperactivation. In this
      review, we reflect on two examples of how short time administration of such
      neutralizing antibodies can block two distinct inflammatory consequences of viral
      infection. First, we review recent findings that blockade of IL-10/IL-10R
      interaction can resolve chronic viral infection and second, we reflect on how
      neutralization of the chemokine CXCL10 can abrogate virus-induced type 1
      diabetes.

PMID- 16603447
TI  - Radioprotective effect of transferrin targeted citicoline liposomes.
AB  - The high level of expression of transferrin receptors (Tf-R) on the surface of
      endothelial cells of the blood-brain-barrier (BBB) had been widely utilized to
      deliver drugs to the brain. The primary aim of this study was to use transferrin
      receptor mediated endocytosis as a pathway for the rational development of holo
      transferrin coupled liposomes for drug targeting to the brain. Citicoline is a
      neuroprotective agent used clinically to treat for instance Parkinson disease,
      stroke, Alzheimer's disease and brain ischemia. Citicoline does not readily cross
      the BBB because of its strong polar nature. Hence, citicoline was used as a model
      drug. (Citicoline liposomes have been prepared using
      dipalmitoylphosphatidylcholine (DPPC) or distearoylphosphatidylcholine (DSPC) by
      dry lipid film hydration-extrusion method). The effect of the use of liposomes
      composed of DPPC or DSPC on their citicoline encapsulation efficiency and their
      stability in vitro were studied. Transferrin was coupled to liposomes by a
      technique which involves the prevention of scavenging diferric iron atoms of
      transferrin. The coupling efficiency of transferrin to the liposomes was studied.
      In vitro evaluation of transferrin-coupled liposomes was performed for their
      radioprotective effect in radiation treated cell cultures. In this study, OVCAR-3
      cells were used as a model cell type over-expressing the Tf-R and human umbilical
      vein endothelial cells (HUVEC) as BBB endothelial cell model. The average
      diameter of DPPC and DSPC liposomes were 138 +/- 6.3 and 79.0 +/- 3.2 nm,
      respectively. The citicoline encapsulation capacity of DPPC and DSPC liposomes
      was 81.8 +/- 12.8 and 54.9 +/- 0.04 microg/micromol of phospholipid,
      respectively. Liposomes prepared from DSPC showed relatively better stability
      than DPPC liposomes at 37 degrees C and in the presence of serum. Hence, DSPC
      liposomes were used for transferrin coupling and an average of 46-55 molecules of
      transferrin were present per liposome. Free citicoline has shown radioprotective
      effect at higher doses tested. Interestingly, encapsulation of citicoline in
      pegylated liposomes significantly improved the radioprotective effect by 4-fold
      compared to free citicoline in OVCAR-3 but not in HUVEC. Further, citicoline
      encapsulation in transferrin-coupled liposomes has significantly improved the
      radioprotective effect by approximately 8-fold in OVCAR-3 and 2-fold in HUVEC
      cells with respect to the free drug. This is likely due to the entry of
      citicoline into cells via transferrin receptor mediated endocytosis. In
      conclusion, our results suggest that low concentrations of citicoline
      encapsulated in transferrin-coupled liposomes could offer therapeutic benefit in
      treating stroke compared to free citicoline.

PMID- 16603448
TI  - Bcl-2 siRNA induced apoptosis and increased sensitivity to 5-fluorouracil and
      HCPT in HepG2 cells.
AB  - To investigate the changes in drug sensitivity of Bcl-2 siRNA transfected HepG2
      cells. Bcl-2 siRNA and negative siRNA expression vector were constructed and
      stably transfected into HepG2 cells. RT-PCR and Immunofluorescence were used to
      detect the target gene expression. Western Blotting was used to detect Bcl-2, Bax
      and caspase-3 protein expressiom. Drug sensitivity of the cells to 5-fluorouracil
      (5-FU) and 10-hydroxycamptothecin (HCPT) were analyzed with MTT and flow
      cytometry. Results were following: (1) the mRNA and protein expression level of
      Bcl-2 in Bcl-2 siRNA stable transfectants were reduced compared with negative
      siRNA transfected or untreated cells. Accordingly, Bax protein expression had no
      change and caspase-3 protein expression showed significantly be up regulated; (2)
      MTT results showed that Bcl-2 siRNA transfectants had higher cell inhibitory
      rates after treated with 5-FU or HCPT; (3) flow cytometry results demonstrated
      that sub G1 population increased in Bcl-2 siRNA transfected cells compared with
      negative siRNA or untreated cells. After addition 5-FU (1300 mg/l) and HCPT (0.72
      mg/l), Bcl-2 siRNA cells showed higher sub G1 population than negative siRNA or
      untreated cells. siRNA targeting Bcl-2 gene can specifically down-regulate Bcl-2
      expression, increased Bax/Bcl-2 ratio expression and caspase-3 activity in HepG2
      cells, which lead to increase cells spontaneous apoptosis and sensitize cells to
      5-FU or HCPT. Bcl-2 siRNA may be a potential therapy agent against human
      hepatoblastoma.

PMID- 16603449
TI  - Sustained release nanoparticulate formulation containing antioxidant-ellagic acid
      as potential prophylaxis system for oral administration.
AB  - The aim of the present work was to develop ellagic acid (EA) loaded poly(d,l
      lactide-co-glycolide) (PLGA) nanoparticles for oral administration. PLGA
      nanoparticles were prepared by a method based on the concept of emulsion
      diffusion-evaporation by using polyethylene glycol (PEG) 400 as a cosolvent for
      solubilizing the drug. While developing this method, didodecyldimethylammomium
      bromide (DMAB) and polyvinyl alcohol (PVA), alone and in combination with
      chitosan (CS) were employed. DMAB stabilized particles were the smallest of all
      the formulations with a particle size of 148.5 nm. PVA alone gave particles of
      269.7 nm but a blend with CS (80:20) resulted in an increase in particle size
      (359.6 +/- 23.6 nm). Initial release of EA from nanoparticles in pH 7.4 phosphate
      buffer was rapid, followed by a slower sustained release. Release rates followed
      the order PVA > PVA-CS > DMAB. Release rate from the PLGA-DMAB particles was
      slowest, which is attributed to higher hydrophobicity of DMAB as compared to PVA,
      preventing diffusion of drug out of polymeric matrix. Insolubility of CS at
      alkaline pH could have retarded the release in case of PVA-CS system. In situ
      intestinal permeability study of pure drug and the drug encapsulated in
      nanoparticles prepared using PVA, PVA-CS blend and DMAB as stabilizer in rats
      showed 66, 75, 73 and 87% permeation, respectively. EA showed good free radical
      scavenging effect in a yeast cell culture model as well as in a cell free system.

PMID- 16603450
TI  - A sustained release dosage form of acyclovir for buccal application: an
      experimental study in dogs.
AB  - Acyclovir is an antiviral agent and it has been particularly used for the
      treatment of herpes simplex infections. The treatment of infection in the oral
      cavity is often difficult, because of insufficient drug concentration in saliva
      when acyclovir is administered via the oral route in conventional tablet form for
      systemic uptake. Therefore, it was aimed to prepare a tablet for buccal
      administration and to investigate its effectiveness by performing in vitro and in
      vivo experiments.The solubility (1.559-4.584) and octanol/water partition
      coefficients ( - 2.176 to - 1.625) of the acyclovir were investigated at
      different pH conditions. A series of tablet formulations were prepared for buccal
      application and their dissolution properties were determined in artificial saliva
      medium. The effect of tablet ingredients on the release rate and mucoadhesion
      force was investigated. The dissolution properties of commercially available
      acyclovir tablets were also determined in the artificial gastric juice. Franz
      type diffusion cells were used to determine acyclovir penetration through buccal
      mucosa from prepared buccal tablets. Selected buccal tablets, commercial tablets
      and intravenous acyclovir solutions were administered to mongrel dogs and drug
      levels in the blood determined by HPLC.A pharmacokinetic model for buccal
      application was also developed and blood concentrations were calculated
      theoretically and compared with the experimental results. Prepared buccal tablets
      were found to be effective for the treatment of viral infections locally within
      the oral cavity and also for systemic treatment.

PMID- 16603451
TI  - Targeted brain delivery of AZT via transferrin anchored pegylated albumin
      nanoparticles.
AB  - Hydrophilic drugs/peptides have poor cross Blood-brain permeability. Various drug
      delivery systems with diverse surfacial characteristics have been reported for
      effective translocation of drugs across Blood-brain barrier. In present
      investigation, the potential of engineered albumin nanoparticles was evaluated
      for brain specific delivery after intravenous administration. Long circulatory
      PEGylated albumin nanoparticles encapsulating water-soluble antiviral drug
      azidothymidine (AZT) were prepared by ultra-emulsification method using chemical
      cross-linking by glutaraldehyde. Surface of the PEGylated nanoparticles was
      modified by anchoring transferrin as a ligand for brain targeting. Nanoparticles
      were characterized for their size, polydispersity, surfacial charge, drug loading
      and in vitro drug release. Fluorescence studies revealed the enhanced uptake of
      transferrin-anchored nanoparticles in the brain tissues when compared with
      unmodified nanoparticles. In vivo evaluation was carried out on albino rats to
      evaluate tissue distribution of engineered nanoparticles after intravenous
      administration. A significant ((*)P < 0.01) enhancement of brain localization of
      AZT was observed for transferrin anchored pegylated albumin nanopariticles (Tf
      PEG-NPs). Hence, the specific role of transferrin ligand on nanoparticles for
      brain targeting was confirmed.

PMID- 16603452
TI  - Assessing gay and bisexual men's outcome expectancies for sexual risk under the
      influence of alcohol and drugs.
AB  - Alcohol and substance use plays a complex role in sexual behavior among gay and
      bisexual men. Data from 779 gay and bisexual men who reported sex with a casual
      partner in the past 3 months were collected in November 2002 at two large
      lesbian, gay, and bisexual community events in New York City. Participants
      reporting any unprotected anal receptive or insertive sex scored significantly
      higher in outcome expectancies for sexual risk taking while using drugs or
      alcohol, as did HIV-positive men and men with a higher rate of lifetime sexually
      transmitted infections. Sexual compulsivity, romantic obsessions, drug use,
      unprotected anal receptive sex, and HIV serostatus successfully predicted outcome
      expectancies for sexual risk while under the influence. Therapists and other
      health and social service providers working with gay and bisexual men should
      explore the connection between sexual risk and being under the influence to
      uncover psychosocial mechanisms related to this phenomenon.

PMID- 16603453
TI  - When problem servers pour in problematic places: Alcoholic beverage servers'
      willingness to serve patrons beyond intoxication.
AB  - Our objective was to examine alcoholic beverage servers' willingness to over
      serve as an explanation for intoxication that occurs in drinking establishments.
      Survey data were collected in 2000 from 911 alcoholic beverage servers in the
      State of Indiana, USA, with a grant from Indiana University. Chi-squared,
      analysis of variance, and step-wise regression were used to examine the influence
      of personal factors, location factors, management policies and practices, and
      larger societal control efforts on willingness to over-serve. Our findings
      support the need to examine managements' economic motivation and servers'
      personal drinking patterns as motivations for serving beyond intoxication in
      future research.

PMID- 16603454
TI  - Times and places: Process evaluation of a peer-led HIV prevention intervention.
AB  - Here we present results from a process evaluation of a peer-led HIV prevention
      intervention. The Risk Avoidance Partnership, conducted from 2001 to 2005,
      trained active drug users to be peer health advocates (PHAs) to provide harm
      reduction materials and information to their peers. Results indicate that PHAs
      actively conducted harm reduction outreach both when partnered with staff and on
      their own time. Although PHAs conducted most of their outreach in public
      locations, they also provided drug users with harm reduction materials at
      critical moments in places where HIV risky behaviors were likely to occur. PHAs
      were credible and trusted sources of information to their drug-using peers who
      sought PHAs out for HIV prevention materials. Process evaluations of successful
      HIV prevention interventions are necessary to understand how and why such
      interventions work for further intervention refinement.

PMID- 16603455
TI  - Correlates of alcohol consumption and tobacco use among tea industry workers of
      Assam.
AB  - An epidemiological study on alcohol and tobacco (smoking and nonsmoked tobacco)
      use was carried out in tea garden population of Assam, one of the largest
      agroindustries of India. A total sample of 2,264 individuals (male, 1,033;
      female, 1,231) aged 15 years and older was interviewed in 2002-2003 to collect
      information about alcohol and tobacco use using a predesigned and pretested
      questionnaire. Age-adjusted prevalence of alcohol consumption was 59.2% (male,
      69.3%; female, 54%). Smoking was more common among males (13.2%) than females
      (2%). However, use of nonsmoked tobacco was almost as popular among female
      (71.9%) as among males (75.3%). More than half of the respondents (54.7%) were
      multiple users of alcohol and tobacco. Prevalence of alcohol consumption,
      nonsmoked tobacco use, and smoking among the young age group (15-24 years) was
      32.2%, 52.5%, and 2.2%, respectively. Prevalence of smoking increased with age,
      and more than a quarter of males above 54 years were smokers. Similar age trends
      in the prevalence of alcohol and nonsmoked tobacco was not observed.
      Sociodemographic correlates, like education, occupation, and marital status,
      emerged as important predictors of substance uses irrespective of sex.
      Association of income with substance use was weak in this study, perhaps due to
      homogeneity of income level. Users of alcohol and tobacco were mostly illiterate,
      manual workers, and widows/widowers. However, smokers were more common among
      sedentary worker. Not withstanding the limitations of the study, the findings of
      the study are useful for planning interventional strategy to control alcohol and
      tobacco use for better health outcome.

PMID- 16603457
TI  - Multiple substance dependence and course of alcoholism among Alaska native men
      and women.
AB  - Alcohol dependence among Native Americans and Alaska Natives is twice that found
      in the general population. Alaska Natives are 7 times more likely to die of
      alcohol-related problems. This study investigated differences in the course and
      consequences of alcoholism and co-occurring polysubstance dependence in a sample
      of 582 alcohol-dependent Alaska Natives undergoing inpatient lifetime treatment
      in Anchorage between 1994 and 1999. Mean age was 33.9 years. Information on
      lifetime psychiatric symptoms and disorders was collected by using the Semi
      Structured Assessment for the Genetics of Alcoholism (SSAGA), a research
      diagnostic interview. Results indicate that in addition to alcohol dependence,
      the majority of subjects were dependent on other substances. Marijuana dependence
      was most common, followed by dependence on cocaine and opiates. Compared with
      subjects not dependent on any other drugs, subjects with co-occurring alcohol and
      opiate dependence showed significant differences in relation to age of first
      regular drink, intoxication, tolerance and withdrawal symptoms, number of medical
      problems, and number of psychological problems. More research and specific
      clinical interventions are needed for alcohol- and opiate-dependent Alaska
      Natives. Findings indicate the need for prevention and interventions in alcohol
      and illicit drug abuse in this population at an early age.

PMID- 16603458
TI  - Validity and consistency of self-reports regarding substance use in general
      research volunteers, including regular cannabis users and schizophrenia patients.
AB  - This study investigated the validity of self-reports of substance use in 69 low
      level substance users from the general community of Perth, Australia,
      volunteering for electrophysiological research, between 2002 and 2003. The
      participants included regular cannabis users and schizophrenia patients. Self
      reports of recent use (last 24 hours) highly agreed with urine screen results
      (kappa = 0.91). Self-reports of past use (lifetime and last 12 months) had poor
      moderate consistency based on correlations among dependence (measured with SDS,
      FTND, SMAST, CAGE), frequency, and use duration. Therefore, under some
      conditions, self-reports are valid for recent use and only moderately consistent
      for past substance use in general research participants.

PMID- 16603456
TI  - Trends in production, trafficking, and consumption of methamphetamine and cocaine
      in Mexico.
AB  - Over the past decade, Mexico has experienced a significant increase in
      trafficking of cocaine and trafficking and production of methamphetamine. An
      estimated 70% of United States cocaine originating in South America passes
      through the Central America-Mexico corridor. Mexico-based groups are now believed
      to control 70%-90% of methamphetamine production and distribution in the United
      States. Increased availability of these drugs at reduced prices has led to a
      parallel rise in local drug consumption. Methamphetamine abuse is now the primary
      reason for seeking drug abuse treatment in a number of cities, primarily in
      northwestern Mexico. Although cocaine and methamphetamine use have been linked
      with the sex trade and high-risk behaviors, such as shooting gallery attendance
      and unprotected sex in other settings, comparatively little is known about the
      risk behaviors associated with use of these drugs in Mexico, especially for
      methamphetamines. We review historical aspects and current trends in cocaine and
      methamphetamine production, trafficking, and consumption in Mexico, with special
      emphasis on the border cities of Ciudad Juarez and Tijuana. Additionally, we
      discuss the potential public health consequences of cocaine use and the recent
      increase in methamphetamine use, especially in regards to the spread of
      bloodborne and other infections, in an effort to inform appropriate public health
      interventions.

PMID- 16603459
TI  - Client predictors of treatment retention and completion in a program for homeless
      veterans.
AB  - This study assessed the value of a specific set of client variables in predicting
      treatment retention and completion of a rehabilitation program for homeless
      veterans. Participants were 596 (22 female) military veterans admitted to the
      Palo Alto, California Veterans Administration domicilary program between 1992 and
      1995. Information was collected on a number of demographic and background
      characteristics previously used to predict treatment retention and outcomes.
      Results indicated that clients who were younger, female, and currently diagnosed
      with a depressive disorder, showed the highest rates of treatment retention and
      completion, whereas a current personality disorder diagnosis or history of
      psychiatric treatment was related to poorer rates of retention and completion.
      These results may be informative for identifying ways to modify this and other
      similar treatments to apply to a larger client population. The study's
      limitations were noted.

PMID- 16603460
TI  - Reliability testing and validation of the drug attitude scale.
AB  - This study was designed to provide reliability testing and validity information
      of the Drug Attitude Scale (DAS). One hundred twenty-eight subjects were drawn
      from a residential substance abuse(1) treatment program within a community mental
      health center. Seventy-five percent of the subjects were males and 25% were
      females. Age ranged from 18 to 58 years. For the entire sample, coefficient alpha
      was found to be 0.87. Reliability estimates for the two subscales were also found
      to be quite similar. Clinical construct validity utilizing factor analysis
      strongly support the two-dimensional nature of the DAS and the accuracy of the
      instrument's scoring key. Initial testing of the DAS suggests that the scale
      represent a useful addition to the area of substance user assessment and
      rehabilitation.

PMID- 16603462
TI  - Type III secretion system-associated toxins, proteases, serotypes, and antibiotic
      resistance of Pseudomonas aeruginosa isolates associated with keratitis.
AB  - The association between possession of toxin gene-related type III secretory
      system, protease profiles, O serotypes, and antibiotic resistance patterns was
      characterized genetically and phenotypically in 46 keratitis isolates of
      Pseudomonas aeruginosa. There was no significant difference in exoU or exoS
      prevalence among the keratitis strains. Distinct protease profiles were seen in
      isolates harboring either exoU or exoS genes. One hundred percent (13/13) of
      serotype E (O:11) strains contained type III secretion system-associated
      cytotoxin gene exoU. Multidrug resistance was identified in 4% of Australian and
      29% of Indian isolates. None of the Australian isolates was resistant to
      ciprofloxacin. In general, the rate of multidrug resistance in the exoU positive
      cytotoxic and serotype E (O:11) strains was significantly higher than in exoS
      positive invasive strains (p < 0.01). The results suggest that multidrug
      resistance may be more commonly associated with the corneal isolates of P.
      aeruginosa having type III secretion system-associated cytotoxin gene exoU and
      belonging to serotype E (O:11) group.

PMID- 16603461
TI  - Sensory denervation modulates eIF-2 alpha kinase expression in the rabbit
      lacrimal gland.
AB  - PURPOSE: To investigate the hypothesis that sensory denervation of the rabbit
      lacrimal gland results in dysregulation of protein synthesis. We used
      differential display of mRNA to identify genes associated with protein synthesis
      and secretion that may be altered in this situation. METHODS: New Zealand white
      rabbits underwent unilateral sensory denervation by the ablation of the
      trigeminal ganglion. After 7 days, the denervated and contralateral control
      lacrimal glands were removed. The effects of denervation on gene expression were
      carried out using differential mRNA display. Northern and Western blot analyses
      were used to verify differential gene expression. RESULTS: Differential mRNA
      display identified the gene heme-regulated inhibitor eukaryotic initiation factor
      2 alpha kinase (HRI eIF-2a kinase) in the lacrimal gland, the expression of which
      was reduced in the denervated lacrimal gland. The sequenced fragment from
      differential display showed 94% identity to rabbit HRI eIF-2a kinase. The
      decreased expression of HRI eIF-2a kinase was confirmed by Northern and Western
      blots, and measurement of HRI eIF-2a kinase phosphorylation activity in the
      lacrimal gland after ablation of sensory neurons showed that it was significantly
      decreased compared with that of normal and control lacrimal glands. CONCLUSIONS:
      The results suggest that loss of sensory innervation has a role in the lacrimal
      gland, contributing to the expression of HRI eIF-2a kinase, a pivotal negative
      regulator of protein synthesis. A reduction in control of protein synthesis may
      lead to the translation of repressed messages associated with cell stress
      responses.

PMID- 16603463
TI  - Phosphorylation of p27(KIP1) in the mitotic cells of the corneal epithelium.
AB  - PURPOSE: The mechanism in regulation of the cell cycle and proliferation of
      corneal epithelium in the homeostatic ocular surface remains unclear. The aim of
      this study is to examine the expression of p27(KIP1) and its phosphorylation in
      corneal epithelium. METHODS: The eyes of C57BL/6 mice (7 weeks old) were
      enucleated. Formalin-fixed and paraffin-embedded tissue sections were examined
      using immunohistochemistry with anti-p27(KIP1), threonine 187 phosphorylated
      p27(KIP1) (T187-phospho-p27), and phosphorylated Histon H3 (pHiston H3)
      antibodies. Anti-T187-phospho-p27 and anti-pHiston H3 polyclonal antibodies were
      used for parallel immunofluorescent staining. RESULTS: pHiston H3-immunopositive
      cells were noted in basal cells of the corneal epithelium. At high magnification
      of DAPI nuclear staining, mitotic and non-mitotic cells were observed in corneal
      basal layer. p27(KIP1)-positive nuclei were detected in corneal basal cells,
      where non-mitotic basal cells were located. In contrast, mitotic cells showed
      under detectable level on p27(KIP1) immunoreactivity. Immunoreactivity for T187
      phospho-p27 was detected in basal cells of the corneal epithelium. At high
      magnification, it was confirmed that the immunopositive cells were mitotic cells.
      Immunoreactivity of T187-phospho-p27 as well as pHiston H3 was localized in the
      same corneal basal cells using double-staining immunohistochemistry. CONCLUSIONS:
      These results suggested that degradation of p27(KIP1) regulates progression into
      mitosis in corneal basal cells.

PMID- 16603464
TI  - Activation of corneal fibroblast-derived matrix metalloproteinase-2 by tryptase.
AB  - PURPOSE: The presence of the active form of matrix metalloproteinase (MMP)-2 and
      an increased concentration of tryptase are characteristics of tear fluid of
      individuals with vernal keratoconjunctivitis. Although tryptase does not mediate
      the activation of purified MMP-2, we have now examined whether it might activate
      MMP-2 in the presence of cultured human corneal fibroblasts. METHODS: Corneal
      fibroblasts were cultured in the absence or presence of tryptase, and the
      activation status of MMP-2 was determined by gelatin zymography. RESULTS: MMP-2
      released from corneal fibroblasts was activated by exogenous tryptase. This
      effect was not mediated by protease-activated receptor 2 or the plasmin
      plasminogen system, and it was not apparent on incubation of tryptase with medium
      conditioned by corneal fibroblasts. It was inhibited by tissue inhibitor of
      metalloproteinase (TIMP)-2 but not by TIMP-1. CONCLUSIONS: Tryptase activates MMP
      2 released from corneal fibroblasts. This action requires the presence of the
      cells themselves and might be responsible for the presence of activated MMP-2 in
      tear fluid of individuals with vernal keratoconjunctivitis.

PMID- 16603465
TI  - Specular microscopy ancillary study methods for donor endothelial cell density
      determination of Cornea Donor Study images.
AB  - PURPOSE: To describe reliable methods for determining central corneal endothelial
      cell density (ECD) in a multicenter eye bank study. METHODS: The Specular
      Microscopy Reading Center utilized a dual-grading procedure and adjudication
      process to classify image quality and determine ECD for a subset of donor
      endothelial images obtained in the Specular Microscopy Ancillary Study, which is
      part of the Cornea Donor Study. Two certified readers classified images as
      analyzable (excellent, good, fair) or unanalyzable and determined the ECD using a
      variable frame technique. An adjudicator also evaluated the images if quality
      classifications by the two readers differed by one grade, if any reader found the
      image unanalyzable, and/or if the ECD determination between the two readers was
      >or= 5%. RESULTS: Image quality categorization by the two readers was identical
      for 441 (64%) of 688 donor images. The ECD differed by < 5% for 442 (69%) of the
      645 analyzable images. The ECD determined by the adjudicator was < 5% different
      than the ECD determined by at least one reader for 193 (95%) of the 203 remaining
      images. CONCLUSIONS: The dual-grading and adjudication procedures produce
      reliable, reproducible assessments of image quality and ECD. The importance of
      two independent readings is evident in that image quality ratings differed
      between the two readers by one grade in 36% of all images and ECD counts differed
      by >or=5% for 31% of analyzable images.

PMID- 16603466
TI  - Visual electrophysiological features of two naturally occurring mouse models with
      retinal dysfunction.
AB  - PURPOSE: We developed two strains of mouse with retinal dysfunction, named the
      ICR-derived retinal dysfunction (IRD)1 and IRD2, from one male ICR mouse with a
      retinal dysfunction but a normal fundus. The purpose of this study was to
      describe the features of retinal dysfunction in both mutant mice. METHODS:
      Scotopic and photopic electroretinograms (ERGs) were recorded from IRD1 and IRD2
      mice at 1 month of age to evaluate retinal function, and then the structures of
      the retinas in both mutant mice were observed by light microscopy at 1 and 3
      months of age. In a mating study, the inheritance pattern and the genetic
      relation of IRD1 and IRD2 mice were defined. RESULTS: At 1 month of age, IRD1
      mice showed affected scotopic and photopic ERGs, and IRD2 mice exhibited normal
      photopic but affected scotopic ERGs. The retinal structures of both mutant mice
      remained normal even at 3 months of age. The IRD1, and IRD2 phenotypes showed an
      autosomal recessive pattern of inheritance and in the IRD1 backcross offspring
      some mice that had only cone dysfunction were seen in addition to normal, IRD1,
      and IRD2 phenotypes. All F1 (IRD1 x IRD2) offspring exhibited IRD2 phenotype, rod
      dysfunction. CONCLUSIONS: IRD1 and IRD2 mice had affected rod systems caused by a
      homozygous mutation in the same rod function-related gene, and additionally IDR1
      mice had affected cone systems caused by a homozygous mutation in the cone
      function-related gene, without apparent anatomical abnormalities in the retinas
      of either mutant mice even at 3 months of age. We believe that these mice could
      be new spontaneous animal models for the study of human inherited retinal
      disorders.

PMID- 16603467
TI  - Activation of AP-1 and increased synthesis of MMP-9 in the rabbit retina induced
      by lipid hydroperoxide.
AB  - PURPOSE: We identified the temporal expression of activator protein-1 (AP-1) and
      matrix metalloproteinases (MMPs) after linoleic acid hydroperoxide (LHP)
      induction of retinal neovascularization. METHODS: After injection of LHP into the
      vitreous of rabbits, samples were collected for AP-1 binding activity and mRNA
      for MMP-9 and MMPs activity. AP-1 binding activity was measured by
      electrophoretic mobility shift assay. MMP-9 activity was measured by zymography
      and mRNA by quantitative RT-PCR. RESULTS: AP-1 binding activity was increased at
      1-3 hr. MMP-9 mRNA levels were increased at 3 hr in the neural retina and by 12
      hr in the retinal pigment epithelium (RPE) layer. MMP-9 proteolytic activity was
      elevated within the neural retina and within the vitreous and in the RPE
      interphotoreceptor matrix (IPM) at 12 hr and peaked at 24 hr or 4 days.
      CONCLUSIONS: LHP increases the transcription factor AP-1 which in turn may
      regulate retinal MMP-9 synthesis during neovascularization.

PMID- 16603468
TI  - Protective effect of hepatocyte growth factor against degeneration of the retinal
      pigment epithelium and photoreceptor in sodium iodate-injected rats.
AB  - PURPOSE: To investigate the possible protective effect of hepatocyte growth
      factor (HGF) against degeneration of photoreceptors and retinal pigment
      epithelium (RPE) in vivo. METHODS: Sprague-Dawley (SD) rats received an
      intravitreal injection of HGF in the right eye. The left eye was injected with
      vehicle as a control. Two days after the intravitreal injections, rats were
      administered 40 mg/kg of sodium iodate (NaIO3) intravenously. Scotopic ERGs were
      elicited by different stimulus intensities with a maximum luminance of 0.84 log
      cds/m2. To evaluate RPE function, the azide response was evoked by intravenous
      injection of 0.1 mg sodium azide. These electrophysiological measurements were
      conducted on days 4, 7, 14, and 28 after the NaIO3 injections. After recording
      ERGs or azide response, animals were sacrificed for quantification of the
      histological change and immunohistochemical analysis using antibodies against RPE
      65. RESULTS: The threshold for the scotopic b-wave was significantly lower in HGF
      treated eyes than in untreated control eyes (p < 0.005), and maximum b-wave
      amplitudes (Vbmax) were significantly larger in HGF-treated eyes (p < 0.05)
      across all experimental time points after NaIO3 injection. Azide response
      amplitudes were significantly larger in the HGF-treated eyes than in the
      untreated eyes (p < 0.05). The structure of the outer retina was preserved to a
      greater degree in the HGF-treated eyes than in the untreated eyes (p < 0.05).
      Immunohistochemical analysis demonstrated that irregular alignment of the outer
      nuclear layer was confined to the retinal area that was not stained with RPE 65.
      CONCLUSIONS: Our results indicated that an intravitreal injection of HGF provided
      significant protection against degeneration of the photoreceptor and RPE induced
      by systemic administration of NaIO3. This suggests that HGF could be used as a
      therapeutic agent for degeneration of photoreceptors as well as RPE.

PMID- 16603471
TI  - The interface of genetics and clinical psychiatry. Introduction.

PMID- 16603469
TI  - A method for chorioretinal oxygen tension measurement.
AB  - PURPOSE: To report an optical imaging system that was developed to measure oxygen
      tension (pO2) in the chorioretinal vasculatures. The feasibility of the system
      for the measurement of changes in pO2 separately in the retinal and choroidal
      vasculatures was established in rat eyes by varying the fraction of inspired
      oxygen and inhibiting nitric oxide activity. METHODS: Our optical section
      phosphorescence imaging system was modified to provide quantitative measurements
      of pO2 separately in the retinal and choroidal vasculatures. A narrow laser line
      was projected at an angle on the retina after intravenous injection of an oxygen
      sensitive probe (Pd-porphyrin), and phosphorescence emission was imaged. A
      frequency-domain approach allowed measurements of the phosphorescence lifetime by
      varying the phase relationship between the modulated excitation laser light and
      sensitivity of the imaging camera. Chorioretinal pO2 was measured while varying
      the fraction of inspired oxygen and during intravenous infusion of Nomega-nitro-L
      arginine (Nomega-NLA), a nonselective nitric oxide synthase inhibitor. RESULTS:
      The systemic arterial pO2 varied according to the fraction of inspired oxygen.
      The pO2 in the retinal and choroidal vasculatures increased as the fraction of
      inspired oxygen was increased. Compared with baseline, choroidal pO2 decreased
      during infusion of Nomega-NLA, whereas the pO2 in the retinal vasculatures
      remained relatively unchanged. The choroidal pO2 decreased markedly with each
      incremental increase in Nomega-NLA infusion rate, in the range 1-6 mg/min, and
      there was no additional change in the choroidal pO2 at Nomega-NLA infusion rates
      above 6 mg/min. CONCLUSIONS: An optical method combining pO2 phosphorescence
      imaging with chorioretinal optical sectioning was established that can
      potentially be applied for better understanding of retinal and choroidal oxygen
      dynamics in physiologic and pathologic states.

PMID- 16603470
TI  - Small optic cup sizes among women using tamoxifen: assessment with scanning laser
      ophthalmoscopy.
AB  - PURPOSE: There is a substantial literature showing that the selective estrogen
      receptor modulator tamoxifen can block swelling-activated chloride channels, such
      as those in astrocytes. This study aimed to test the hypothesis that anatomic
      characteristics consistent with swelling may be measured within the optic nerve
      head (ONH) of tamoxifen users whose ONH appearance is considered within normal
      limits. METHODS: Indices of ONH topography were measured using the Heidelberg
      Retina Tomograph II (HRT) for two populations of women ages 40-69 years: (1)
      subjects using tamoxifen (20 mg/day) as adjuvant therapy after successful primary
      treatment for breast cancer and (2) control subjects not using any hormonal
      medication. All subjects had excellent visual acuity (with 20/20 or better in the
      test eye), and all appeared to be free of eye disease, as based on conventional
      photographic assessment. The study design was cross-sectional. The various ONH
      indices were assessed as functions of the duration of tamoxifen use. RESULTS: The
      optic cups of short-term tamoxifen users (<or=2 years) were significantly smaller
      in both the lateral and axial directions than the optic cups of the control
      subjects. Of the 27 short-term users, 23 had cup volumes smaller than the median
      value for the control subjects. The cup sizes of long-term users (> 2 years,
      <or=5 years) were not distinguishable from those of the control subjects. The
      presence of small cups among short-term users did not depend on subjects' medical
      histories prior to tamoxifen use. Disk margin indices were not related
      significantly to the duration of tamoxifen use. CONCLUSIONS: Small cup sizes
      consistent with localized subclinical swelling are not rare among short-term
      tamoxifen users. Thus, small cups are not likely to be a manifestation of a
      cumulative-dose toxicity. Instead, they probably result from other causes,
      possibly involving the action of tamoxifen on estrogen receptors. Further
      investigation with longitudinal and interventional methodologies is needed to
      definitively interpret the results.

PMID- 16603472
TI  - Carving chaos: genetics and the classification of mood and psychotic syndromes.
AB  - Though Kraepelin's century-old division of major mental illness into mood
      disorder and schizophrenia remains in place, debate abounds over the most
      appropriate classification. Although these arguments previously rested solely on
      clinical grounds, they now are rooted in genetics and neurobiology. This article
      reviews evidence from the fields of genetic epidemiology, linkage, association,
      cytogenetics, and gene expression. Taken together, these data suggest some
      overlap in the genes that predispose to bipolar disorder and schizophrenia. One
      gene, DAOA (D-amino acid oxidase activator, also known as G72), has been
      repeatedly implicated as an overlap gene, while DISC1 and others may constitute
      additional shared susceptibility genes. Further, some evidence implicates
      syndromes of co-occurring mood and psychotic symptoms in association with the
      putative risk alleles in overlap genes. From a nosologic perspective, the
      existence of overlap genes, coupled with the genotype-phenotype correlations
      discovered to date, supports the reality of the much debated schizoaffective
      disorder. Potential non-overlap syndromes--such as nonpsychotic bipolar disorder
      or cyclothymic temperament, on the one hand, and negative symptoms or the deficit
      syndrome, on the other--could turn out to have their own unique genetic
      determinants. If genotypes are to be the anchor points of a clinically useful
      system of classification, they must ultimately be shown to inform prognosis,
      treatment, and prevention. No gene variants have yet met these tests in bipolar
      disorder or schizophrenia.

PMID- 16603473
TI  - Schizophrenia: do the genetics and neurobiology of neuregulin provide a
      pathogenesis model?
AB  - The sequencing of the human genome and an emerging dense map of markers across
      the human genome have spawned new approaches to search for risk genes for human
      diseases with complex genetics. These approaches are particularly relevant to the
      search for risk genes for bipolar disorder and schizophrenia. A gene called
      neuregulin 1 has been reported to be a risk gene for schizophrenia. This article
      reviews aspects of the genetics, cellular neurobiology, and biochemistry of
      neuregulin 1 and attempts to integrate several observations from disparate fields
      into a model for the pathogenesis of schizophrenia. The model outlines
      experimental approaches that may, in the future, shed more light on its validity.

PMID- 16603474
TI  - Neuroimaging-genetic paradigms: a new approach to investigate the pathophysiology
      and treatment of cognitive deficits in schizophrenia.
AB  - Cognitive impairment is a prominent and debilitating feature of schizophrenia.
      Genetic predisposition likely accounts for a large proportion of these cognitive
      deficits. Direct associations between candidate genes and cognitive dysfunction
      have been difficult to establish, however, largely due to the subtle effects of
      these genes on observable behavior. Neuroimaging techniques can provide a
      sensitive means to bridge the neurobiology of genes and behavior. Here we
      illustrate the use of neuroimaging-genetics paradigms to elaborate the
      relationship between genes and cognitive dysfunction in schizophrenia. After
      reviewing principles important for the selection of genes, neuroimaging
      techniques, and subjects, we describe how imaging-genetics investigations have
      helped clarify the contribution of five candidate genes (COMT, GRM3, G72, DISC1,
      and BDNF) to cognitive deficits in schizophrenia. The potential of this approach
      for improving patient care will depend on its ability to predict outcomes with
      greater accuracy and sensitivity than current clinical measures.

PMID- 16603475
TI  - Pharmacogenetics, race, and psychiatry: prospects and challenges.
AB  - Although the field of pharmacogenetics has existed for nearly 50 years, it has
      begun to enter mainstream clinical practice only recently. Researchers and
      clinicians have now demonstrated that a wide assortment of genetic variants
      influence how individuals respond to medications. Many of these variants are
      relevant for psychiatry, affecting how patients respond to most antidepressants,
      antipsychotics, anxiolytics, and mood stabilizers. Enthusiasts hope that
      pharmacogenetics will soon usher in a new era of individualized medicine.
      However, determining the practical relevance of pharmacogenetic variants remains
      difficult, in part because of problems with study design and replication, and in
      part because a host of nongenetic factors (including age, diet, environmental
      exposures, and comorbid diseases) also influence how individuals respond to
      medications. Since individualized pharmacogenetic assessment remains difficult,
      some researchers have argued that race provides a convenient proxy for individual
      genetic variation, and that clinicians should choose medications and doses
      differently for different races. This approach remains extremely controversial
      because of the complexity of the genetic structure of the human population, the
      complexity of gene-environment interactions, and the complexity of the meanings
      of race in the United States.

PMID- 16603476
TI  - Genetic counseling in psychiatry.
AB  - While psychiatrists may commonly discuss family history in clinical practice,
      there has been little systematic research documenting the role and effectiveness
      of genetic counseling for psychiatric disorders. In the coming years, the
      expected identification of susceptibility genes for psychiatric disorders may
      bring new opportunities and expectations from patients and families for the
      clinical translation of research findings in psychiatric genetics. We review
      evidence for possible increasing demand for genetic counseling, particularly if
      specific genes related to psychiatric disorders are identified. We then explore
      both the potential role of genetic counseling for psychiatric disorders and the
      issues involved in conveying genetic information in the clinical setting. Further
      research regarding the effectiveness of counseling interventions, as well as
      additional efforts directed at genetics education for clinicians, will be needed
      if emerging advances in genetic research are to be incorporated into clinical
      practice.

PMID- 16603477
TI  - Does Haber's law apply to human sensory irritation?
AB  - Irritation of the eyes, nose, and throat by airborne chemicals--also referred to
      as "sensory irritation"--is an important endpoint in both occupational and
      environmental toxicology. Modeling of human sensory irritation relies on
      knowledge of the physical chemistry of the compound(s) involved, as well as the
      exposure parameters (concentration and duration). A reciprocal relationship
      between these two exposure variables is postulated under Haber's law, implying
      that protracted, low-level exposures may be toxicologically equivalent to brief,
      high-level exposures. Although time is recognized as having an influence on
      sensory irritation, the quantitative predictions of Haber's Law have been
      addressed for only a handful of compounds in human experimental studies. We have
      conducted a systematic literature review that includes a semiquantitative
      comparison of psychophysical data extracted from controlled human exposure
      studies versus. the predictions of Haber's law. Studies containing relevant data
      involved exposures to ammonia (2), chlorine (2), formaldehyde (1), inorganic
      dusts such as calcium oxide (1), and the volatile organic compound 1-octene (1).
      With the exception of dust exposure, varying exposure concentration has a
      proportionally greater effect on sensory irritation than does changing exposure
      duration. For selected time windows, a more generalized power law model (c(n) x t
      = k) rather than Haber's law per se (c x t = k) yields reasonably robust
      predictions. Complicating this picture, however, is the frequent observation of
      intensity-time "plateauing," with time effects disappearing, or even reversing,
      after a relatively short period, depending on the test compound. The implications
      of these complex temporal dynamics for risk assessment and standard setting have
      been incompletely explored to date.

PMID- 16603478
TI  - A modeling study of the effect of gravity on airflow distribution and particle
      deposition in the lung.
AB  - Inhalation of particles generated as a result of thermal degradation from fire or
      smoke, as may occur on spacecraft, is of major health concern to space-faring
      countries. Knowledge of lung airflow and particle transport under different
      gravity environments is required to addresses this concern by providing
      information on particle deposition. Gravity affects deposition of particles in
      the lung in two ways. First, the airflow distribution among airways is changed in
      different gravity environments. Second, particle losses by sedimentation are
      enhanced with increasing gravity. In this study, a model of airflow distribution
      in the lung that accounts for the influence of gravity was used for a
      mathematical description of particle deposition in the human lung to calculate
      lobar, regional, and local deposition of particles in different gravity
      environments. The lung geometry used in the mathematical model contained five
      lobes that allowed the assessment of lobar ventilation distribution and variation
      of particle deposition. At zero gravity, it was predicted that all lobes of the
      lung expanded and contracted uniformly, independent of body position. Increased
      gravity in the upright position increased the expansion of the upper lobes and
      decreased expansion of the lower lobes. Despite a slight increase in predicted
      deposition of ultrafine particles in the upper lobes with decreasing gravity,
      deposition of ultrafine particles was generally predicted to be unaffected by
      gravity. Increased gravity increased predicted deposition of fine and coarse
      particles in the tracheobronchial region, but that led to a reduction or even
      elimination of deposition in the alveolar region for coarse particles. The
      results from this study show that existing mathematical models of particle
      deposition at 1 G can be extended to different gravity environments by simply
      correcting for a gravity constant. Controlled studies in astronauts on future
      space missions are needed to validate these predictions.

PMID- 16603479
TI  - Inhibition of pan neurotrophin receptor p75 attenuates diesel particulate-induced
      enhancement of allergic airway responses in C57/B16J mice.
AB  - Recent investigations have linked neurotrophins, including nerve growth factor
      (NGF), neurotrophin-3 (NT-3), and brain-derived neurotrophic factor (BDNF), to
      allergic airways diseases. Antibody blockade of NGF attenuates airway resistance
      in allergic mice. Diesel exhaust particle (DEP) exposure has been linked to
      asthma exacerbation in many cities with vehicular traffic congestion. We tested
      the hypothesis that DEP-induced enhancement of the hallmark features of allergic
      airway disease in a murine model is dependent on the function of the pan
      neurotrophin receptor p75. Ovalbumin (OVA)-sensitized C57B1/6J mice were
      intranasally instilled with an antibody against the p75 receptor or saline alone
      1 h before OVA challenge. The mice were then exposed nose-only to the PM2.5
      fraction of SRM2975 DEP or air alone for 5 h beginning 1 h after OVA challenge.
      Two days later, air-exposed OVA-allergic mice developed a small but insignificant
      increase in methacholine-induced airflow obstruction relative to air-exposed,
      vehicle-sensitized mice. DEP-exposed OVA-allergic mice had a significantly
      greater degree of airway obstruction than all other groups. Instillation of anti
      p75 significantly attenuated the DEP-induced increase in airway obstruction in
      OVA-allergic mice to levels similar to non-sensitized mice. The DEP-induced
      exacerbation of allergic airway responses may, in part, be mediated by
      neurotrophins.

PMID- 16603480
TI  - Butyrylcholinesterase in guinea pig lung lavage: a novel biomarker to assess lung
      injury following inhalation exposure to nerve agent VX.
AB  - Respiratory disturbances play a central role in chemical warfare nerve agent
      (CWNA) induced toxicity; they are the starting point of mass casualty and the
      major cause of death. We developed a microinstillation technique of inhalation
      exposure to nerve agent VX and assessed lung injury by biochemical analysis of
      the bronchoalveolar lavage fluid (BALF). Here we demonstrate that normal guinea
      pig BALF has a significant amount of cholinesterase activity. Treatment with
      Huperzine A, a specific inhibitor of acetylcholinesterase (AChE), showed that a
      minor fraction of BALF cholinesterase is AChE. Furthermore, treatment with
      tetraisopropyl pyrophosphoramide (iso-OMPA), a specific inhibitor of
      butyrylcholinesterase (BChE), inhibited more than 90% of BChE activity,
      indicating the predominance of BChE in BALF. A predominance of BChE expression in
      the lung lavage was seen in both genders. Substrate specific inhibition indicated
      that nearly 30% of the cholinesterase in lung tissue homogenate is AChE. BALF and
      lung tissue AChE and BChE activities were strongly inhibited in guinea pigs
      exposed for 5 min to 70.4 and 90.4 microg/m3 VX and allowed to recover for 15
      min. In contrast, BALF AChE activity was increased 63% and 128% and BChE activity
      was increased 77% and 88% after 24 h of recovery following 5 min inhalation
      exposure to 70.4 microg/m3 and 90.4 mg/m3 VX, respectively. The increase in BALF
      AChE and BChE activity was dose dependent. Since BChE is synthesized in the liver
      and present in the plasma, an increase in BALF indicates endothelial barrier
      injury and leakage of plasma into lung interstitium. Therefore, a measure of
      increased levels of AChE and BChE in the lung lavage can be used to determine the
      chronology of barrier damage as well as the extent of lung injury following
      exposure to chemical warfare nerve agents.

PMID- 16603481
TI  - Effects on androstenedione in male workers exposed to urban stressors.
AB  - The aim of this study is to evaluate whether occupational exposure to urban
      stressors could cause alterations in androstenedione plasma levels in male
      traffic policemen compared to a control group. After excluding the principal
      confounding factors, traffic policemen were matched with controls by age, working
      life, body mass index (BMI), drinking habit, and habitual soy intake in diet. One
      hundred and ten traffic policemen and 110 controls were included in the study. In
      male traffic policemen, mean androstenedione values were significantly lower
      compared to controls. The distribution of androstenedione values in traffic
      policemen and in controls was significant. Our results suggest that the
      occupational exposure to chemical urban stressors, interacting with and adding to
      the psychosocial ones, could alter androstenedione plasma concentrations in
      traffic policemen compared to a control group. According to our previous
      research, androstenedione could be used as an early biological marker, valuable
      for the group to be employed in occupational settings, even before the onset of
      the endocrine reproductive health diseases.

PMID- 16603482
TI  - A critique of "fine particulate air pollution and total mortality among elderly
      Californians, 1973-2002" by James E. Enstrom.

PMID- 16603484
TI  - Crambene induces pancreatic acinar cell apoptosis via the activation of
      mitochondrial pathway.
AB  - We investigated the apoptotic pathway activated by crambene (1-cyano-2-hydroxy-3
      butene), a plant nitrile, on pancreatic acinar cells. As evidenced by annexin V
      FITC staining, crambene treatment for 3 h induced the apoptosis but not necrosis
      of pancreatic acini. Caspase-3, -8, and -9 activities in acini treated with
      crambene were significantly higher than in untreated acini. Treatment with
      caspase-3, -8, and -9 inhibitors inhibited annexin V staining, as well as caspase
      3 activity, pointing to an important role of these caspases in crambene-induced
      acinar cell apoptosis. The mitochondrial membrane potential was collapsed, and
      cytochrome c was released from the mitochondria in crambene-treated acini.
      Neither TNF-alpha nor Fas ligand levels were changed in pancreatic acinar cells
      after crambene treatment. These results provide evidence for the induction of
      pancreatic acinar cell apoptosis in vitro by crambene and suggest the involvement
      of mitochondrial pathway in pancreatic acinar cell apoptosis.

PMID- 16603485
TI  - Cooperative interactions among intestinal GATA factors in activating the rat
      liver fatty acid binding protein gene.
AB  - GATA-4, GATA-5, and GATA-6 are endodermal zinc-finger transcription factors that
      activate numerous enterocytic genes. GATA-4 and GATA-6 but not GATA-5 are present
      in adult murine small intestinal enterocytes, and we now report the simultaneous
      presence of all three GATA factors in murine small intestinal enterocytes before
      weaning age. An immunohistochemical survey detected enterocytic GATA-4 and GATA-6
      at birth and 1 wk of age and GATA-5 at 1 wk but not birth. Interactions among
      GATA factors were explored utilizing a transgene constructed from the proximal
      promoter of the rat liver fatty acid binding protein gene (Fabp1). GATA-4 and
      GATA-5 but not GATA-6 activate the Fabp1 transgene through a cognate binding site
      at -128. A dose-response assay revealed a maximum in transgene activation by both
      factors, where additional factor did not further increase transgene activity.
      However, at saturated levels of GATA-4, additional transgene activation was
      achieved by adding GATA-5 expression construct, and vice versa. Similar
      cooperativity occurred with GATA-5 and GATA-6. Identical interactions were
      observed with a target transgene consisting of a single GATA site upstream of a
      minimal promoter. Furthermore, GATA-4 and GATA-5 or GATA-5 and GATA-6 bound to
      each other in solution. These results are consistent with tethering of one GATA
      factor to the Fabp1 promoter through interaction with a second GATA factor to
      produce increased target gene activation. Cooperative target gene activation was
      specific to an intestinal cell line and may represent a mechanism by which genes
      are activated in the small intestinal epithelium during the period before
      weaning.

PMID- 16603486
TI  - A model for the pulsatile secretion of gonadotropin-releasing hormone from
      synchronized hypothalamic neurons.
AB  - Cultured gonadotropin-releasing hormone (GnRH) neurons have been shown to express
      GnRH receptors. GnRH binding to its receptors activates three types of G-proteins
      at increasing doses. These G-proteins selectively activate or inhibit GnRH
      secretion by regulating the intracellular levels of Ca2+ and cAMP. Based on these
      recent observations, we build a model in which GnRH plays the roles of a feedback
      regulator and a diffusible synchronizing agent. We show that this GnRH-regulated
      GnRH-release mechanism is sufficient for generating pulsatile GnRH release. The
      model reproduces the observed effects of some key drugs that disturb the GnRH
      pulse generator in specific ways. Simulations of 100 heterogeneous neurons
      revealed that the synchronization mediated by a common pool of diffusible GnRH is
      robust. The population can generate synchronized pulsatile signals even when all
      the individual GnRH neurons oscillate at different amplitudes and peak at
      different times. These results suggest that the positive and negative effects of
      the autocrine regulation by GnRH on GnRH neurons are sufficient and robust in
      generating GnRH pulses.

PMID- 16603487
TI  - Autologous morphogen gradients by subtle interstitial flow and matrix
      interactions.
AB  - Cell response to extracellular cues is often driven by gradients of morphogenetic
      and chemotactic proteins, and therefore descriptions of how such gradients arise
      are critical to understanding and manipulating these processes. Many of these
      proteins are secreted in matrix-binding form to be subsequently released
      proteolytically, and here we explore how this feature, along with small dynamic
      forces that are present in all tissues, can affect pericellular protein
      gradients. We demonstrate that 1), pericellular gradients of cell-secreted
      proteins can be greatly amplified when secreted by the cell in matrix-binding
      form as compared to a nonmatrix-interacting form; and 2), subtle flows can drive
      significant asymmetry in pericellular protein concentrations and create
      transcellular gradients that increase in the direction of flow. This study thus
      demonstrates how convection and matrix-binding, both physiological
      characteristics, combine to allow cells to create their own autologous
      chemotactic gradients that may drive, for example, tumor cells and immune cells
      into draining lymphatic capillaries.

PMID- 16603488
TI  - Clustering of cyclic-nucleotide-gated channels in olfactory cilia.
AB  - Olfactory cilia contain the known components of olfactory signal transduction,
      including a high density of cyclic-nucleotide-gated (CNG) channels. CNG channels
      play an important role in mediating odor detection. The channels are activated by
      cAMP, which is formed by a G-protein-coupled transduction cascade. Frog olfactory
      cilia are 25-200 microm in length, so the spatial distribution of CNG channels
      along the length should be important in determining the sensitivity of odor
      detection. We have recorded from excised cilia and modeled diffusion of cAMP into
      a cilium to determine the spatial distribution of the CNG channels along the
      ciliary length. The proximal segment, which in frog is the first 20% of the
      cilium, appears to express a small fraction of the CNG channels, whereas the
      distal segment contains the majority, mostly clustered in one region.

PMID- 16603489
TI  - The DNA binding activity of p53 displays reaction-diffusion kinetics.
AB  - The tumor suppressor protein p53 plays a key role in maintaining the genomic
      stability of mammalian cells and preventing malignant transformation. In this
      study, we investigated the intracellular diffusion of a p53-GFP fusion protein
      using confocal fluorescence recovery after photobleaching. We show that the
      diffusion of p53-GFP within the nucleus is well described by a mathematical model
      for diffusion of particles that bind temporarily to a spatially homogeneous
      immobile structure with binding and release rates k1 and k2, respectively. The
      diffusion constant of p53-GFP was estimated to be Dp53-GFP=15.4 microm2 s-1,
      significantly slower than that of GFP alone, DGFP=41.6 microm2 s-1. The reaction
      rates of the binding and unbinding of p53-GFP were estimated as k1=0.3 s-1 and
      k2=0.4 s-1, respectively, values suggestive of nonspecific binding. Consistent
      with this finding, the diffusional mobilities of tumor-derived sequence-specific
      DNA binding mutants of p53 were indistinguishable from that of the wild-type
      protein. These data are consistent with a model in which, under steady-state
      conditions, p53 is latent and continuously scans DNA, requiring activation for
      sequence-specific DNA binding.

PMID- 16603490
TI  - In vivo quantitative studies of dynamic intracellular processes using
      fluorescence correlation spectroscopy.
AB  - It has been a significant challenge to quantitatively study the dynamic
      intracellular processes in live cells. These studies are essential for a thorough
      understanding of the underlying mechanisms regulating the signaling pathways and
      the transitions between cell cycle stages. Our studies of Cdc20, an important
      mitotic checkpoint protein, throughout the cell cycle demonstrate that
      fluorescence correlation spectroscopy is a powerful tool for in vivo quantitative
      studies of dynamic intracellular processes. In this study, Cdc20 is found to be
      present primarily in a large complex (>1 Mda) during interphase with a diffusion
      constant of 1.8+/-0.1 microm2/s and a concentration of 76+/-24 nM, consistent
      with its association with the APC/C. During mitosis, however, a proportion of
      Cdc20 dissociates from APC/C at a rate of 12 pM/s into a soluble pool with a
      diffusion constant of 19.5+/-5.0 microm2/s, whose size is most consistent with
      free Cdc20. This free pool accumulates to 50% of total Cdc20 (approximately 40
      nM) during chronic activation of the mitotic checkpoint but disappears during
      mitotic exit at a rate of 31 pM/s. The observed changes in the biochemical
      assembly states of Cdc20 closely correlate to the known temporal pattern of the
      activity of APC/CCdc20 in mitosis. Photon counting histograms reveal that both
      complexes contain only a single molecule of Cdc20. The underlying mechanisms of
      the activities of APC/CCdc20 throughout the cell cycle are discussed in light of
      our experimental observations.

PMID- 16603491
TI  - A new model of weak acid permeation through membranes revisited: does Overton
      still rule?
AB  - According to a recent publication by Thomae, A. V., H. Wunderli-Allenspach, and
      S. D. Kramer (2005. Biophys. J. 89:1802-1811), membrane bilayers are well
      permeable to the charged species of aromatic carboxylic acids. At physiological
      pH, the anions were claimed to be the major diffusing species. In contrast,
      calculation of the Born energy barrier predicts a 10(5)-fold higher permeability
      for the uncharged (protonated) form. To test the new model, we now have measured
      both the current carried by the salicylate anion through solvent-free planar
      membranes and the amount of protons transported by the neutral species. The
      corresponding membrane permeabilities of the charged and protonated forms were 4
      x 10(-7) cm/s and 1.2 cm/s. These data are in perfect agreement with literature
      data gathered in the last three decades (compare, e.g., Gutknecht, J., and D. C.
      Tosteson. 1973. Science. 182:1258-1261). They indicate that the report by Thomae
      at al. represents an experimental artifact. The well-documented role of neutral
      species in the permeation process of weak acids and bases across artificial and
      natural membranes is not in question. Overton still rules.

PMID- 16603492
TI  - Flexible histone tails in a new mesoscopic oligonucleosome model.
AB  - We describe a new mesoscopic model of oligonucleosomes that incorporates flexible
      histone tails. The nucleosome cores are modeled using the discrete surface-charge
      optimization model, which treats the nucleosome as an electrostatic surface
      represented by hundreds of point charges; the linker DNAs are treated using a
      discrete elastic chain model; and the histone tails are modeled using a
      bead/chain hydrodynamic approach as chains of connected beads where each bead
      represents five protein residues. Appropriate charges and force fields are
      assigned to each histone chain so as to reproduce the electrostatic potential,
      structure, and dynamics of the corresponding atomistic histone tails at different
      salt conditions. The dynamics of resulting oligonucleosomes at different sizes
      and varying salt concentrations are simulated by Brownian dynamics with complete
      hydrodynamic interactions. The analyses demonstrate that the new mesoscopic model
      reproduces experimental results better than its predecessors, which modeled
      histone tails as rigid entities. In particular, our model with flexible histone
      tails: correctly accounts for salt-dependent conformational changes in the
      histone tails; yields the experimentally obtained values of histone-tail mediated
      core/core attraction energies; and considers the partial shielding of
      electrostatic repulsion between DNA linkers as a result of the spatial
      distribution of histone tails. These effects are crucial for regulating chromatin
      structure but are absent or improperly treated in models with rigid histone
      tails. The development of this model of oligonucleosomes thus opens new avenues
      for studying the role of histone tails and their variants in mediating gene
      expression through modulation of chromatin structure.

PMID- 16603493
TI  - Probabilistic modeling of rosette formation.
AB  - Rosetting, or forming a cell aggregate between a single target nucleated cell and
      a number of red blood cells (RBCs), is a simple assay for cell adhesion mediated
      by specific receptor-ligand interaction. For example, rosette formation between
      sheep RBC and human lymphocytes has been used to differentiate T cells from B
      cells. Rosetting assay is commonly used to determine the interaction of Fc gamma
      receptors (FcgammaR) expressed on inflammatory cells and IgG coated on RBCs.
      Despite its wide use in measuring cell adhesion, the biophysical parameters of
      rosette formation have not been well characterized. Here we developed a
      probabilistic model to describe the distribution of rosette sizes, which is
      Poissonian. The average rosette size is predicted to be proportional to the
      apparent two-dimensional binding affinity of the interacting receptor-ligand pair
      and their site densities. The model has been supported by experiments of rosettes
      mediated by four molecular interactions: FcgammaRIII interacting with IgG, T cell
      receptor and coreceptor CD8 interacting with antigen peptide presented by major
      histocompatibility molecule, P-selectin interacting with P-selectin glycoprotein
      ligand 1 (PSGL-1), and L-selectin interacting with PSGL-1. The latter two are
      structurally similar and are different from the former two. Fitting the model to
      data enabled us to evaluate the apparent effective two-dimensional binding
      affinity of the interacting molecular pairs: 7.19x10(-5) microm4 for FcgammaRIII
      IgG interaction, 4.66x10(-3) microm4 for P-selectin-PSGL-1 interaction, and
      0.94x10(-3) microm4 for L-selectin-PSGL-1 interaction. These results elucidate
      the biophysical mechanism of rosette formation and enable it to become a
      semiquantitative assay that relates the rosette size to the effective affinity
      for receptor-ligand binding.

PMID- 16603494
TI  - Effects of intracellular and extracellular concentrations of Ca2+, K+, and Cl- on
      the Na+-dependent Mg2+ efflux in rat ventricular myocytes.
AB  - Intracellular Mg2+ concentration ([Mg2+]i) was measured in rat ventricular
      myocytes with the fluorescent indicator furaptra (25 degrees C). After the
      myocytes were loaded with Mg2+, the initial rate of decrease in [Mg2+]i (initial
      Delta[Mg2+]i/Deltat) was estimated upon introduction of extracellular Na+, as an
      index of the rate of Na+-dependent Mg2+ efflux. The initial Delta[Mg2+]i/Deltat
      values with 140 mM [Na+]o were essentially unchanged by the addition of
      extracellular Ca2+ up to 1 mM (107.3+/-8.7% of the control value measured at 0 mM
      [Ca2+]o in the presence of 0.1 mM EGTA, n=5). Intracellular loading of a Ca2+
      chelator, either BAPTA or dimethyl BAPTA, by incubation with its acetoxymethyl
      ester form (5 microM for 3.5 h) did not significantly change the initial
      Delta[Mg2+]i/Deltat: 115.2+/-7.5% (seven BAPTA-loaded cells) and 109.5+/-10.9%
      (four dimethyl BAPTA loaded cells) of the control values measured in the absence
      of an intracellular chelator. Extracellular and/or intracellular concentrations
      of K+ and Cl- were modified under constant [Na+]o (70 mM), [Ca2+]o (0 mM with 0.1
      mM EGTA), and membrane potential (-13 mV with the amphotericin-B-perforated patch
      clamp technique). None of the following conditions significantly changed the
      initial Delta[Mg2+]i/Deltat: 1), changes in [K+]o between 0 mM and 75 mM (65.6+/
      5.0% (n=11) and 79.0+/-6.0% (n=8), respectively, of the control values measured
      at 140 mM [Na+]o without any modification of extracellular and intracellular K+
      and Cl-); 2), intracellular perfusion with K+-free (Cs+-substituted) solution
      from the patch pipette in combination with removal of extracellular K+ (77.7+/
      8.2%, n=8); and 3), extracellular and intracellular perfusion with K+-free and Cl
      -free solutions (71.6+/-5.1%, n=5). These results suggest that Mg2+ is
      transported in exchange with Na+, but not with Ca2+, K+, or Cl-, in cardiac
      myocytes.

PMID- 16603495
TI  - First steps of retinal photoisomerization in proteorhodopsin.
AB  - The early steps (<1 ns) in the photocycle of the detergent solubilized proton
      pump proteorhodopsin are analyzed by ultrafast spectroscopic techniques. A
      comparison to the first primary events in reconstituted proteorhodopsin as well
      as to the well known archaeal proton pump bacteriorhodopsin is given. A dynamic
      Stokes shift observed in fs-time-resolved fluorescence experiments allows a
      direct observation of early motions on the excited state potential energy
      surface. The initial dynamics is dominated by sequentially emerging stretching
      (<150 fs) and torsional (approximately 300 fs) modes of the retinal. The
      different protonation states of the primary proton acceptor Asp-97 drastically
      affect the reaction rate and the overall quantum efficiencies of the
      isomerization reactions, mainly evidenced for time scales above 1 ps. However, no
      major influence on the fast time scales (approximately 150 fs) could be seen,
      indicating that the movement out of the Franck-Condon region is fairly robust to
      electrostatic changes in the retinal binding pocket. Based on fs-time-resolved
      absorption and fluorescence spectra, ground and exited state contributions can be
      disentangled and allow to construct a reaction model that consistently explains
      pH-dependent effects in solubilized and reconstituted proteorhodopsin.

PMID- 16603496
TI  - Solid-state NMR investigation of the membrane-disrupting mechanism of
      antimicrobial peptides MSI-78 and MSI-594 derived from magainin 2 and melittin.
AB  - The mechanism of membrane interaction of two amphipathic antimicrobial peptides,
      MSI-78 and MSI-594, derived from magainin-2 and melittin, is presented. Both the
      peptides show excellent antimicrobial activity. The 8-anilinonaphthalene-1
      sulfonic acid uptake experiment using Escherichia coli cells suggests that the
      outer membrane permeabilization is mainly due to electrostatic interactions. The
      interaction of MSI-78 and MSI-594 with lipid membranes was studied using 31P and
      2H solid-state NMR, circular dichroism, and differential scanning calorimetry
      techniques. The binding of MSI-78 and MSI-594 to the lipid membrane is associated
      with a random coil to alpha-helix structural transition. MSI-78 and MSI-594 also
      induce the release of entrapped dye from POPC/POPG (3:1) vesicles. Measurement of
      the phase-transition temperature of peptide-DiPoPE dispersions shows that both
      MSI-78 and MSI-594 repress the lamellar-to-inverted hexagonal phase transition by
      inducing positive curvature strain. 15N NMR data suggest that both the peptides
      are oriented nearly perpendicular to the bilayer normal, which infers that the
      peptides most likely do not function via a barrel-stave mechanism of membrane
      disruption. Data obtained from 31P NMR measurements using peptide-incorporated
      POPC and POPG oriented lamellar bilayers show a disorder in the orientation of
      lipids up to a peptide/lipid ratio of 1:20, and the formation of nonbilayer
      structures at peptide/lipid ratio>1:8. 2H-NMR experiments with selectively
      deuterated lipids reveal peptide-induced disorder in the methylene units of the
      lipid acyl chains. These results are discussed in light of lipid-peptide
      interactions leading to the disruption of membrane via either a carpet or a
      toroidal-type mechanism.

PMID- 16603497
TI  - The kinetics of nucleated polymerizations at high concentrations: amyloid fibril
      formation near and above the "supercritical concentration".
AB  - The formation of amyloid and other types of protein fibrils is thought to proceed
      by a nucleated polymerization mechanism. One of the most important features
      commonly associated with nucleated polymerizations is a strong dependence of the
      rate on the concentration. However, the dependence of fibril formation rates on
      concentration can weaken and nearly disappear as the concentration increases.
      Using numerical solutions to the rate equations for nucleated polymerization and
      analytical solutions to some limiting cases, we examine this phenomenon and show
      that it is caused by the concentration approaching and then exceeding the
      equilibrium constant for dissociation of monomers from species smaller than the
      nucleus, a quantity we have named the "supercritical concentration". When the
      concentration exceeds the supercritical concentration, the monomer, not the
      nucleus, is the highest-energy species on the fibril formation pathway, and the
      fibril formation reaction behaves initially like an irreversible polymerization.
      We also derive a relation that can be used in a straightforward method for
      determining the nucleus size and the supercritical concentration from
      experimental measurements of fibril formation rates.

PMID- 16603498
TI  - Electrostatic energy calculation on the pH-induced conformational change of
      influenza virus hemagglutinin.
AB  - The pH-induced conformational change of influenza virus hemagglutinin (HA) has
      been investigated by calculating the change of electrostatic energy of the
      fragment of HA2 upon pH change. The average charge and electrostatic free energy
      are calculated as a function of pH for the fusion peptide (residues 1-20 of HA2)
      and the polypeptide of residues 54-77 of HA2 by using the finite difference
      Poisson-Boltzmann method. It is found that as pH decreases from 8 to 5, the
      electrostatic free energy of the fusogenic state is lowered by approximately 2
      kcal/mol and the fusogenic state is less ionized compared to that of the native
      state for both polypeptides. For the fusion peptide at the fusogenic state, most
      of ionizable residues are neutral at acidic pH except Glu-11. For the polypeptide
      of residues 54-77 at the fusogenic state, most of residues except Glu-74 and His
      64 are fully charged between pH 5 and pH 8.

PMID- 16603499
TI  - Interplay of ryanodine receptor distribution and calcium dynamics.
AB  - Spontaneously generated calcium (Ca2+) waves can trigger arrhythmias in
      ventricular and atrial myocytes. Yet, Ca2+ waves also serve the physiological
      function of mediating global Ca2+ increase and muscle contraction in atrial
      myocytes. We examine the factors that influence Ca2+ wave initiation by
      mathematical modeling and large-scale computational (supercomputer) simulations.
      An important finding is the existence of a strong coupling between the ryanodine
      receptor distribution and Ca2+ dynamics. Even modest changes in the ryanodine
      receptor spacing profoundly affect the probability of Ca2+ wave initiation. As a
      consequence of this finding, we suggest that there is information flow from the
      contractile system to the Ca2+ control system and this dynamical interplay could
      contribute to the increased incidence of arrhythmias during heart failure.

PMID- 16603500
TI  - Three-dimensional distribution of ryanodine receptor clusters in cardiac
      myocytes.
AB  - The clustering of ryanodine receptors (RyR2) into functional Ca2+ release units
      is central to current models for cardiac excitation-contraction (E-C) coupling.
      Using immunolabeling and confocal microscopy, we have analyzed the distribution
      of RyR2 clusters in rat and ventricular atrial myocytes. The resolution of the
      three-dimensional structure was improved by a novel transverse sectioning method
      as well as digital deconvolution. In contrast to earlier reports, the mean RyR2
      cluster transverse spacing was measured 1.05 microm in ventricular myocytes and
      estimated 0.97 microm in atrial myocytes. Intercalated RyR2 clusters were found
      interspersed between the Z-disks on the cell periphery but absent in the
      interior, forming double rows flanking the local Z-disks on the surface. The
      longitudinal spacing between the adjacent rows of RyR2 clusters on the Z-disks
      was measured to have a mean value of 1.87 microm in ventricular and 1.69 microm
      in atrial myocytes. The measured RyR2 cluster distribution is compatible with
      models of Ca2+ wave generation. The size of the typical RyR2 cluster was close to
      250 nm, and this suggests that approximately 100 RyR2s might be present in a
      cluster. The importance of cluster size and three-dimensional spacing for current
      E-C coupling models is discussed.

PMID- 16603501
TI  - Structural comparison of the two alternative transition states for folding of TI
      I27.
AB  - TI I27, a beta-sandwich domain from the human muscle protein titin, has been
      shown to fold via two alternative pathways, which correspond to a change in the
      folding mechanism. Under physiological conditions, TI I27 folds by a classical
      nucleation-condensation mechanism (diffuse transition state), whereas at extreme
      conditions of temperature and denaturant it switches to having a polarized
      transition state. We have used experimental Phi-values as restraints in ensemble
      averaged molecular dynamics simulations to determine the ensembles of structures
      representing the two transition states. The comparison of these ensembles
      indicates that when native interactions are substantially weakened, a protein may
      still be able to fold if it can access an alternative transition state
      characterized by a much larger entropic contribution. Analysis of the probability
      distribution of Phi-values derived from ensemble averaged simulations, enables us
      to identify residues that form contacts in some members of the ensemble but not
      in others illustrating that many interactions present in transition states are
      not strictly required for the successful completion of the folding process.

PMID- 16603502
TI  - Lateral diffusion anisotropy and membrane lipid/skeleton interaction in outer
      hair cells.
AB  - The organization of the plasma membrane of cells in lipid domains affects the way
      the membrane interacts with the underlying protein skeleton, which in turn
      affects the lateral mobility of lipid and protein molecules in the membrane.
      Membrane fluidity properties can be monitored by various approaches, the most
      versatile of which is fluorescence recovery after photobleaching (FRAP). We
      extended previous FRAP experiments on isolated cochlear outer hair cells (OHCs)
      by analyzing the two-dimensional pattern of lipid diffusion in the lateral
      membrane of these cells. We found that membrane lipid mobility in freshly
      isolated OHCs is orthotropic, diffusion being faster in the axial direction of
      the cell and slower in the circumferential direction. Increasing the cell's
      turgor pressure by osmotic challenge reduced the axial diffusion constant, but
      had only a slight effect on circumferential diffusion. Our results suggest that
      lipid mobility in the OHC plasma membrane is affected by the presence of the
      cell's orthotropic membrane skeleton. This effect could reflect interaction with
      spectrin filaments or with other membrane skeletal proteins. We also performed a
      number of FRAP measurements in temporal bone preparations preserving the
      structural integrity of the hearing organ. The diffusion rates measured for OHCs
      in this preparation were in good agreement with those obtained in isolated OHCs,
      and comparable to the mobility rates measured on the sensory inner hair cells.
      These observations support the idea that the plasma membranes of both types of
      hair cells share similar highly fluid phases in the intact organ. Lipid mobility
      was significantly slower in the membranes of supporting cells of the organ of
      Corti, which could reflect differences in lipid phase or stronger hindrance by
      the cytoskeleton in these membranes.

PMID- 16603503
TI  - Diffusional anisotropy in collagenous tissues: fluorescence imaging of continuous
      point photobleaching.
AB  - Molecular transport in avascular collagenous tissues such as articular cartilage
      occurs primarily via diffusion. The presence of ordered structures in the
      extracellular matrix may influence the local transport of macromolecules, leading
      to anisotropic diffusion depending on the relative size of the molecule and that
      of extracellular matrix structures. Here we present what we believe is a novel
      photobleaching technique for measuring the anisotropic diffusivity of
      macromolecules in collagenous tissues. We hypothesized that macromolecular
      diffusion is anisotropic in collagenous tissues, depending on molecular size and
      the local organization of the collagen structure. A theoretical model and
      experimental protocol for fluorescence imaging of continuous point photobleaching
      was developed to measure diffusional anisotropy. Significant anisotropy was
      observed in highly ordered collagenous tissues such as ligament, with diffusivity
      ratios>2 along the fiber direction compared to the perpendicular direction. In
      less-ordered tissues such as articular cartilage, diffusional anisotropy was
      dependent on site in the tissue and size of the diffusing molecule. Anisotropic
      diffusion was also dependent on the size of the diffusing molecule, with greatest
      anisotropy observed for larger molecules. These findings suggest that diffusional
      transport of macromolecules is anisotropic in collagenous tissues, with higher
      rates of diffusion along primary orientation of collagen fibers.

PMID- 16603504
TI  - A statistical-mechanical theory of fibril formation in dilute protein solutions.
AB  - We outline a theoretical treatment that describes fibril formation in dilute
      protein solutions. For this, we combine a theory describing self-assembly and
      conformational transition with a description of the lateral association of linear
      chains. Our statistical-mechanical model is able to predict the mean degree of
      polymerization and the length of the fibrils and their precursors, as well as the
      weight fractions of the different aggregated species in solution. We find that
      there appear to exist two regimes as a function of concentration, and as a
      function of the free energies of protein association: one in which low-molecular
      weight compounds dominate and one in which the fibrils do. The transition between
      these regimes can be quite sharp, and becomes sharper as more filaments are
      allowed to associate into a single fibril. The fraction of fibrils consisting of
      less than the maximum allowed number of filaments turns out to be negligible, in
      agreement with experimental studies, where the fibril thickness is found to be
      practically monodisperse. In addition, we find that the description of the fibril
      ends has a large effect on the predicted fibril length.

PMID- 16603505
TI  - Development of a novel GFP-based ratiometric excitation and emission pH indicator
      for intracellular studies.
AB  - We report on the development of the F64L/S65T/T203Y/L231H GFP mutant (E2GFP) as
      an effective ratiometric pH indicator for intracellular studies. E2GFP shows two
      distinct spectral forms that are convertible upon pH changes both in excitation
      and in emission with pK close to 7.0. The excitation of the protein at 488 and
      458 nm represents the best choice in terms of signal dynamic range and
      ratiometric deviation from the thermodynamic pK. This makes E2GFP ideally suited
      for imaging setups equipped with the most widespread light sources and filter
      settings. We used E2GFP to determine the average intracellular pH (pH(i)) and
      spatial pH(i) maps in two different cell lines, CHO and U-2 OS, under
      physiological conditions. In CHO, we monitored the evolution of the pH(i) during
      mitosis. We also showed the possibility to target specific subcellular
      compartments such as nucleoli (by fusing E2GFP with the transactivator protein of
      HIV, (Tat) and nuclear promyelocytic leukemia bodies (by coexpression of
      promyelocytic leukemia protein).

PMID- 16603506
TI  - Regulation of intracellular signalling by the terminal membrane proteins of
      members of the Gammaherpesvirinae.
AB  - The human gamma(1)-herpesvirus Epstein-Barr virus (EBV) and the gamma(2)
      herpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV), rhesus rhadinovirus
      (RRV), herpesvirus saimiri (HVS) and herpesvirus ateles (HVA) all contain genes
      located adjacent to the terminal-repeat region of their genomes, encoding
      membrane proteins involved in signal transduction. Designated 'terminal membrane
      proteins' (TMPs) because of their localization in the viral genome, they interact
      with a variety of cellular signalling molecules, such as non-receptor protein
      tyrosine kinases, tumour-necrosis factor receptor-associated factors, Ras and
      Janus kinase (JAK), thereby initiating further downstream signalling cascades,
      such as the MAPK, PI3K/Akt, NF-kappaB and JAK/STAT pathways. In the case of TMPs
      expressed during latent persistence of EBV and HVS (LMP1, LMP2A, Stp and Tip),
      their modulation of intracellular signalling pathways has been linked to the
      provision of survival signals to latently infected cells and, hence, a
      contribution to occasional cellular transformation. In contrast, activation of
      similar pathways by TMPs of KSHV (K1 and K15) and RRV (R1), expressed during
      lytic replication, may extend the lifespan of virus-producing cells, alter their
      migration and/or modulate antiviral immune responses. Whether R1 and K1
      contribute to the oncogenic properties of KSHV and RRV has not been established
      satisfactorily, despite their transforming qualities in experimental settings.

PMID- 16603507
TI  - Hepatitis C virus entry: potential receptors and their biological functions.
AB  - Several cellular molecules have been identified as putative receptors for
      Hepatitis C virus (HCV): CD81 tetraspanin, scavenger receptor class B type I (SR
      BI), mannose-binding lectins DC-SIGN and L-SIGN, low-density lipoprotein
      receptor, heparan sulphate proteoglycans and the asialoglycoprotein receptor. Due
      to difficulties in propagating HCV in cell culture, most of these molecules have
      been identified by analysing their interaction with a soluble, truncated form of
      HCV glycoprotein E2. A recent major step in investigating HCV entry was the
      development of pseudoparticles (HCVpp), consisting of unmodified HCV envelope
      glycoproteins assembled onto retroviral core particles. This system has allowed
      the investigation of the role of candidate receptors in the early steps of the
      HCV life cycle and the data obtained can now be confirmed with the help of a
      newly developed cell-culture system that allows efficient amplification of HCV
      (HCVcc). Interestingly, CD81 and SR-BI have been shown to play direct roles in
      HCVpp and/or HCVcc entry. However, co-expression of CD81 and SR-BI in non-hepatic
      cell lines does not lead to HCVpp entry, indicating that other molecule(s),
      expressed only in hepatic cells, are necessary for HCV entry. In this review, the
      molecules that have been proposed as potential HCV receptors are described and
      the experimental data indicating that CD81 and SR-BI are potentially involved in
      HCV entry are presented.

PMID- 16603508
TI  - Analysis of synthetic peptides from heptad-repeat domains of herpes simplex virus
      type 1 glycoproteins H and B.
AB  - Human herpesviruses enter cells by fusion of their own membrane with a cellular
      membrane through the concerted action of multiple viral proteins and cellular
      receptors. Two conserved viral glycoproteins, gB and gH, are required for herpes
      simplex virus type 1 (HSV-1)-mediated membrane fusion, but little is known of how
      these proteins cooperate during entry. Both glycoproteins were shown to contain
      heptad repeat (HR) sequences predicted to form alpha-helical coiled coils, and
      the inhibitory activity against infection of four sets of synthetic peptides
      corresponding to HR1 and HR2 of gB and gH was tested. The interactions between
      these HR peptides were also investigated by circular dichroism, native
      polyacrylamide-gel electrophoresis and size exclusion high-performance liquid
      chromatography. gH coiled-coil peptides were more effective than gB coiled-coils
      peptides in inhibiting virus infectivity. The peptides did not impair fusion when
      added to cells immediately after infection. In contrast, inhibition of infection
      was observed, albeit to various extents, when peptides were added to virus before
      or during inoculation. The results of biophysical analyses were indicative of the
      existence of an interaction between HR1 and HR2 of gH and suggest that the HRs of
      gB and gH do not interact with each other.

PMID- 16603509
TI  - Induction of cytokine expression by herpes simplex virus in human monocyte
      derived macrophages and dendritic cells is dependent on virus replication and is
      counteracted by ICP27 targeting NF-kappaB and IRF-3.
AB  - Macrophages and dendritic cells (DCs) play essential roles in host defence
      against microbial infections. In the present study, it is shown that human
      monocyte-derived macrophages and DCs express both type I and type III interferons
      (IFNs) [IFN-alpha, IFN-beta and interleukin 28 (IL-28), IL-29, respectively],
      tumour necrosis factor alpha and the chemokines CCL5 and CXCL10 after herpes
      simplex virus 1 (HSV-1) infection. The cytokine-inducing activity of HSV-1 was
      dependent on viability of the virus, because UV-inactivated virus did not induce
      a cytokine response. Pretreatment of the cells with IFN-alpha or IL-29 strongly
      enhanced the HSV-1-induced cytokine response. Both IFN-alpha and IL-29 decreased
      viral immediate-early (IE) gene infected-cell protein 27 (ICP27) transcription,
      suggesting that IL-29 possesses antiviral activity against HSV-1 comparable to
      that of IFN-alpha. Macrophage infection with HSV-1 lacking functional ICP27 (d27
      1 virus) resulted in strongly enhanced cytokine mRNA expression and protein
      production. In contrast, viruses lacking functional IE genes ICP0 and ICP4
      induced cytokine responses comparable to those of the wild-type viruses. The
      activation of transcription factors IRF-3 and NF-kappaB was strongly augmented
      when macrophages were infected with the ICP27 mutant virus. Altogether, the
      results demonstrate that HSV-1 both induces and inhibits the antiviral response
      in human cells and that the type III IFN IL-29, together with IFN-alpha,
      amplifies the antiviral response against the virus. It is further identified that
      viral IE-gene expression interferes with the antiviral response in human
      macrophages and ICP27 is identified as an important viral protein counteracting
      the early innate immune response.

PMID- 16603510
TI  - Trypsin increases pseudorabies virus production through activation of the ERK
      signalling pathway.
AB  - Extracellular proteases that are expressed in primary and secondary foci of viral
      infection are potentially important mediators of infectious inflammatory
      processes. For some viruses, such as influenza virus and rotaviruses, proteases
      such as trypsin enhance infectivity by a direct proteolytic effect on some virion
      proteins. By using an in vitro model of herpesvirus infection, the possibility
      that proteases modulate the viral cycle through signalling delivered to the
      infected cell was investigated. It is reported that exposure of pseudorabies
      virus-infected cells to trypsin increased virus production. Moreover, this
      treatment induced synergistic and sustained activation of the extracellular
      signal-regulated kinase (ERK) 1/2 signalling pathway, which appeared to be
      necessary for this increased viral production. These results suggest that
      herpesviruses could take advantage of the inflammatory context and particularly
      of the presence of proteases to increase their replication. Thus, these data
      point to a potentially important role of extracellular proteases in herpesvirus
      infection.

PMID- 16603511
TI  - Role of the cellular protein hDaxx in human cytomegalovirus immediate-early gene
      expression.
AB  - Human cytomegalovirus (HCMV) immediate-early (IE) transcription is stimulated by
      virion phosphoprotein pp71, the product of gene UL82. It has previously been
      shown that pp71 interacts with the cellular protein hDaxx and, in the studies
      presented here, the significance of this interaction was investigated for HCMV IE
      gene expression. In co-transfection experiments, the presence of hDaxx increased
      the transcriptional response of the HCMV major IE promoter (MIEP) to pp71, but it
      was not possible to determine whether the effect was due to an interaction
      between the two proteins or to stimulation of hDaxx synthesis by pp71. The use of
      small interfering RNA (siRNA) in long- and short-term transfection approaches
      reduced intracellular hDaxx levels to no more than 3 % of normal. Infection of
      hDaxx-depleted cells with herpes simplex virus recombinants containing the HCMV
      MIEP revealed significantly greater promoter activity when hDaxx levels were
      minimal. Similarly, reducing intracellular hDaxx amounts resulted in greater IE
      gene expression during infection with an HCMV mutant lacking pp71, but had no
      effect on IE transcription during infection with wild-type HCMV. The results
      suggest that hDaxx is not important as a positive-acting factor for the
      stimulation of HCMV IE transcription by pp71. Instead, it appears that hDaxx acts
      as a repressor of IE gene expression, and it is proposed here that the
      interaction of pp71 with hDaxx is important to relieve repression and permit
      efficient initiation of productive replication.

PMID- 16603512
TI  - Mixed infection with multiple strains of murine cytomegalovirus occurs following
      simultaneous or sequential infection of immunocompetent mice.
AB  - As with human cytomegalovirus (HCMV) infection of humans, murine CMV (MCMV)
      infection is widespread in its natural host, the house mouse Mus domesticus, and
      may consist of mixed infection with different CMV isolates. The incidence and
      mechanisms by which mixed infection occurs in free-living mice are unknown. This
      study used two approaches to determine whether mixed infection with MCMV could be
      established in laboratory mice. The first utilized two naturally occurring MCMV
      strains, N1 and G4, into which the lacZ gene was inserted by homologous
      recombination. The lacZ gene was used to track recombinant and parental viruses
      in simultaneously coinfected mice. In the second approach, a real-time
      quantitative PCR (qPCR) assay was used to detect viral immediate-early 1 (ie1)
      gene sequences in mice successively coinfected with G4 and then with the K181
      MCMV strain. In both systems, mixed infection was detected in the salivary glands
      and lungs of experimentally infected mice. MCMV-specific antibody in sera and G4
      IE1-specific cytotoxic lymphocyte responses in the spleens of twice-infected mice
      did not prevent reinfection. Finally, the prevalence of mixed infection in free
      living mice trapped in four Australian locations was investigated using real-time
      qPCR to detect ie1 DNA sequences of N1, G4 and K181. Mixed infection with MCMVs
      containing the G4 and K181 ie1 sequences was detected in the salivary glands of
      34.2 % of trapped mice. The observations that mixed infections are common in free
      living M. domesticus and are acquired by immunocompetent mice through
      simultaneous or successive infections are important for vaccine development.

PMID- 16603513
TI  - Epstein-Barr virus origin of lytic replication mediates association of
      replicating episomes with promyelocytic leukaemia protein nuclear bodies and
      replication compartments.
AB  - Epstein-Barr virus (EBV) establishes a latent persistence from which it can be
      reactivated to undergo lytic replication. Late lytic-cycle gene expression is
      linked to lytic DNA replication, as it is sensitive to the same inhibitors that
      block lytic replication, and it has recently been shown that the viral origin of
      lytic replication (ori lyt) is required in cis for late-gene expression. During
      the lytic cycle, the viral genome forms replication compartments, which are
      usually adjacent to promyelocytic leukaemia protein (PML) nuclear bodies. A
      tetracycline repressor DNA-binding domain-enhanced green fluorescent protein
      fusion was used to visualize replicating plasmids carrying a tetracycline
      operator sequence array. ori lyt mediated the production of plasmid replication
      compartments that were associated with PML nuclear bodies. Plasmids carrying ori
      lyt and EBV itself were visualized in the same cells and replicated in similar
      regions of the nucleus, further supporting the validity of the plasmids for
      studying late-gene regulation.

PMID- 16603514
TI  - Raf/MEK/ERK signalling triggers reactivation of Kaposi's sarcoma-associated
      herpesvirus latency.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, primary
      effusion lymphoma and multicentric Castleman's disease. KSHV infection of cells
      produces both latent and lytic cycles of infection. In vivo, the virus is found
      predominantly in the latent state. In vitro, a lytic infection can be induced in
      KSHV-infected cells by treating with phorbol ester (TPA). However, the exact
      signalling events that lead to the reactivation of KSHV lytic infection are still
      elusive. Here, a role is demonstrated for B-Raf/MEK/ERK signalling in TPA-induced
      reactivation of KSHV latent infection. Inhibiting MEK/ERK signalling by using MEK
      specific inhibitors decreased expression of the TPA-induced KSHV lytic-cycle gene
      ORF8. Transfection of BCBL-1 cells with B-Raf small interfering RNA inhibited TPA
      induced KSHV lytic infection significantly. Additionally, overexpression of MEK1
      induced a lytic cycle of KSHV infection in BCBL-1 cells. The significance of
      these findings in understanding the biology of KSHV-associated pathogenesis is
      discussed.

PMID- 16603515
TI  - Double-stranded RNA-binding protein E3 controls translation of viral intermediate
      RNA, marking an essential step in the life cycle of modified vaccinia virus
      Ankara.
AB  - Infection of human cells with modified vaccinia virus Ankara (MVA) activates the
      typical cascade-like pattern of viral early-, intermediate- and late-gene
      expression. In contrast, infection of human HeLa cells with MVA deleted of the
      E3L gene (MVA-DeltaE3L) results in high-level synthesis of intermediate RNA, but
      lacks viral late transcription. The viral E3 protein is thought to bind double
      stranded RNA (dsRNA) and to act as an inhibitor of dsRNA-activated 2'-5'
      oligoadenylate synthetase (2'-5'OA synthetase)/RNase L and protein kinase (PKR).
      Here, it is demonstrated that viral intermediate RNA can form RNase A/T1
      resistant dsRNA, suggestive of activating both the 2'-5'OA synthetase/RNase L
      pathway and PKR in various human cell lines. Western blot analysis revealed that
      failure of late transcription in the absence of E3L function resulted from the
      deficiency to produce essential viral intermediate proteins, as demonstrated for
      vaccinia late transcription factor 2 (VLTF 2). Substantial host cell-specific
      differences were found in the level of activation of either RNase L or PKR.
      However, both rRNA degradation and phosphorylation of eukaryotic translation
      initiation factor-2alpha (eIF2alpha) inhibited the synthesis of VLTF 2 in human
      cells. Moreover, intermediate VLTF 2 and late-protein production were restored in
      MVA-DeltaE3L-infected mouse embryonic fibroblasts from Pkr(0/0) mice. Thus, both
      host-response pathways may be involved, but activity of PKR is sufficient to
      block the MVA molecular life cycle. These data imply that an essential function
      of vaccinia virus E3L is to secure translation of intermediate RNA and, thereby,
      expression of other viral genes.

PMID- 16603516
TI  - Intradermal immune response after infection with Vaccinia virus.
AB  - Although Vaccinia virus (VACV) was used to eradicate smallpox by dermal
      vaccination, there is little information available about the immune response
      induced at the vaccination site. Previously, an intradermal murine model that
      mimics smallpox vaccination was established. Here, this model was used to
      investigate which leukocytes are recruited to the infected lesion and what are
      the kinetics of recruitment. Data presented show that VACV infection induced the
      infiltration of macrophages, followed by granulocytes and lymphocytes. Up to 4
      days post-infection, the major lymphocyte population was TCRgammadelta T cells,
      but thereafter, there was a large recruitment of CD4(+) and CD8(+) T cells.
      Interestingly, the majority of T cells expressed the natural killer-cell marker
      DX5. This report is the first to characterize the local immune response sequence
      to VACV infection and represents a benchmark against which the responses induced
      by genetically modified VACVs may be compared.

PMID- 16603517
TI  - Phylogenetic analysis of the precore/core gene of hepatitis B virus genotypes E
      and A in West Africa: new subtypes, mixed infections and recombinations.
AB  - One hundred and twenty-two new hepatitis B virus (HBV) preC/C sequences and three
      complete genomes from three major countries in West Africa were analysed. The
      majority of sequences were of genotype E and the only other genotype found was
      genotype A. Although for genotype E sequences, the genetic diversity of the
      preC/C gene was about two to three times higher than that of the preS/S gene, it
      was still considerably lower than that for genotype A sequences. The HBV/E preC/C
      gene was related most closely to subgenotype D1 and D2 sequences. Evidence of
      recombination was found in two strains that were of genotype A in the preS/S gene
      and of genotype E in the preC/C gene. The genotype A strains from Cameroon, Mali
      and Nigeria could be divided phylogenetically into three subtypes, A3 and two new
      subtypes, tentatively designated A4 and A5. Each subtype presented a genetic
      diversity of 2.19-3.85 % and intersubtype distances of 4.47-5.97 %.
      Interestingly, one sample from Nigeria showed evidence of a triple recombination
      of genotypes E/D and A, separated by a genotype G-specific insert of 36 bp. Of
      110 patients, 19 (17.3 %) showed a coinfection of genotypes A and E, mostly in
      human immunodeficiency virus-positive children from Cameroon. Thus, in Cameroon,
      where both genotypes coexist, 37 % of all individuals tested had mixed
      infections. The low genetic variability in the preC/C gene of genotype E supports
      our previous speculation about a relatively short evolutionary history of this
      genotype, in contrast to the subtype-rich African genotype A strains.

PMID- 16603518
TI  - Analysis of the entire nucleotide sequence of hepatitis B virus genotype B in the
      Philippines reveals a new subgenotype of genotype B.
AB  - The entire nucleotide sequences were determined for hepatitis B virus (HBV)
      genotype B (HBV/B) genomes extracted from five patients in the Philippines and
      designated GenBank AB219426, AB219427, AB219428, AB219429 and AB219430. The
      serotype of the first four isolates was ayw and that of GenBank AB219430 was adw.
      Divergences of entire sequences were 1.0-2.0 % between the first four isolates
      and 3.8-4.2 % between these four and GenBank AB219430. Phylogenetic-tree analysis
      revealed that, worldwide, HBV/B comprises five subgenotypes: B1, B2, B3, B4 and
      the new Philippines group, designated B5. Divergences of the entire genome
      sequences between four isolates in subgenotype B5 and isolates from other
      countries (subgenotypes) were 4.4-4.8 % with Vietnam (B4), 2.9-3.5 % with
      Indonesia (B3), 4.7-5.1 % with China (B2) and 5.4-6.0 % with Japan (B1).
      Similarly, GenBank AB219430 showed the lowest divergences: 3.4 % with the isolate
      from Indonesia (B3), 5.0 % with Vietnam (B4), 5.4 % with China (B2) and 6.1 %
      with Japan (B1). This is the first report of entire nucleotide sequences of HBV/B
      from the Philippines and the results show that these sequences belong to a new
      subgenotype, B5. The present study identified that HBV/B isolates throughout the
      world are divided genetically into five subgenotypes, the relationships between
      geographical distances and the genetic distances of HBV/B being well-correlated.

PMID- 16603519
TI  - Analysis of mutations in the E6/E7 oncogenes and L1 gene of human papillomavirus
      16 cervical cancer isolates from China.
AB  - Human papillomavirus type 16 (HPV16) has a number of intratypic variants; each
      has a different geographical distribution and some are associated with enhanced
      oncogenic potential. Cervical samples were collected from 223 cervical cancer
      patients and from 196 age-matched control subjects in China. DNA samples were
      amplified by using primers specific for the E6, E7 and partial L1 regions.
      Products were sequenced and analysed. It was found by using a PCR-sequence-based
      typing method that HPV infection rates in China were 92.8 % in cervical cancer
      patients and 15.8 % in healthy controls. HPV16 was detected in 70.4 % of cervical
      cancer patients and in 6.1 % of controls. In HPV16-positive cervical cancers,
      23.6 % belonged to the prototype, 65.5 % were of the Asian variant, 5.5 % were of
      African type 1 and 3.6 % were European variants, whilst only one was a new
      variant that differed from any variant published so far. Prevalences of HPV16 E6
      D25E and E113D variants were 67.3 and 9 %, respectively. In addition to D25E and
      E113D, the following E6 variations were found in this study: R129K, E89Q, S138C,
      H78Y, L83V and F69L. The results also showed that the prevalences of three hot
      spots of E7 nucleotide variation, N29S, S63F and a silent variation, nt T846C,
      were 70.2 % (33/47), 51.1 % (24/47) and 61.7 % (29/47), respectively. The
      following L1 variations were found in this study: S377A, K387E, E378D, K382E and
      T379P. It was also found that the average age of Asian variant-positive cervical
      cancer patients (42.98+/-10.43 years) was 7.56 years lower than that of prototype
      positive patients (50.54+/-10.91). It is suggested that the high frequency of
      HPV16 Asian variants might contribute to the high incidence of cervical cancer in
      China.

PMID- 16603520
TI  - Genome of a novel circovirus of starlings, amplified by multiply primed rolling
      circle amplification.
AB  - The genus Circovirus comprises small non-enveloped viruses with a circular single
      stranded DNA genome. By using PCR with degenerate primers, a novel circovirus
      (starling circovirus, StCV) was detected in spleen samples of wild starlings
      (Sturnus vulgaris and Sturnus unicolor) found dead during an epidemic outbreak of
      septicaemic salmonellosis in northeastern Spain. Using a specific PCR, StCV was
      also detected in apparently healthy birds from the same population. The genome
      was amplified using multiply primed rolling-circle amplification and cloned. Open
      reading frames (ORFs) with similarities to the replication-associated protein and
      the capsid protein of circoviruses as well as an additional ORF encoding a
      protein of 106 aa were evident from the sequence. Phylogenetic analysis of
      circovirus genomes revealed the highest degree of similarity (67.1 %) between
      StCV and canary circovirus. A similar analysis of the evolutionarily conserved
      cytochrome b gene of the circovirus host species revealed a strict co-evolution
      of circoviruses with their hosts; however, the circoviruses showed about a
      threefold higher genetic divergence than their hosts.

PMID- 16603521
TI  - Hypoxic-response elements in the oncolytic parvovirus Minute virus of mice do not
      allow for increased vector production at low oxygen concentration.
AB  - Vectors derived from the autonomous parvovirus Minute virus of mice, MVM(p), are
      promising tools for the gene therapy of cancer. The validation of their in vivo
      anti-tumour effect is, however, hampered by the difficulty to produce high-titre
      stocks. In an attempt to increase vector titres, host cells were subjected to low
      oxygen tension (hypoxia). It has been shown that a number of viruses are produced
      at higher titres under these conditions. This is the case, among others, for
      another member of the family Parvoviridae, the erythrovirus B19 virus. Hypoxia
      stabilizes a hypoxia-inducible transcription factor (HIF-1alpha) that interacts
      with a 'hypoxia-responsive element' (HRE), the consensus sequence of which
      ((A)/(G)CGTG) is present in the B19 and MVM promoters. Whilst the native P4
      promoter was induced weakly in hypoxia, vector production was reduced
      dramatically, and adding HRE elements to the P4 promoter of the vector did not
      alleviate this reduction. Hypoxia has many effects on cell metabolism. Therefore,
      even if the P4 promoter is activated, the cellular factors that are required for
      the completion of the parvoviral life cycle may not be expressed.

PMID- 16603522
TI  - Analysis of human coronavirus 229E spike and nucleoprotein genes demonstrates
      genetic drift between chronologically distinct strains.
AB  - Historically, coronaviruses have been recognized as a cause of minor respiratory
      infections in humans. However, the recent identification of three novel human
      coronaviruses, one causing severe acute respiratory syndrome (SARS), has prompted
      further examination of these viruses. Previous studies of geographically and
      chronologically distinct Human coronavirus 229E (HCoV-229E) isolates have found
      only limited variation within S gene nucleotide sequences. In contrast, analysis
      of the S genes of contemporary Human coronavirus OC43 variants identified in
      Belgium revealed two distinct viruses circulating during 2003 and 2004. Here, the
      S and N gene sequences of 25 HCoV-229E variants identified in Victoria,
      Australia, between 1979 and 2004 in patients with symptomatic infections were
      determined. Phylogenetic analysis showed clustering of the isolates into four
      groups, with evidence of increasing divergence with time. Evidence of positive
      selection in the S gene was also established.

PMID- 16603523
TI  - Sialic acid is a receptor determinant for infection of cells by avian Infectious
      bronchitis virus.
AB  - The importance of sialic acid for infection by avian Infectious bronchitis virus
      (IBV) has been analysed. Neuraminidase treatment rendered Vero, baby hamster
      kidney and primary chicken kidney cells resistant to infection by the IBV
      Beaudette strain. Sialic acid-dependent infection was also observed with strain
      M41 of IBV, which infects primary chicken kidney cells but not cells from other
      species. In comparison with Influenza A virus and Sendai virus, IBV was most
      sensitive to pre-treatment of cells with neuraminidase. This finding suggests
      that IBV requires a greater amount of sialic acid on the cell surface to initiate
      an infection compared with the other two viruses. In previous studies, with
      respect to the haemagglutinating activity of IBV, it has been shown that the
      virus preferentially recognizes alpha2,3-linked sialic acid. In agreement with
      this finding, susceptibility to infection by IBV was connected to the expression
      of alpha2,3-linked sialic acid as indicated by the reactivity with the lectin
      Maackia amurensis agglutinin. Here, it is discussed that binding to sialic acid
      may be used by IBV for primary attachment to the cell surface; tighter binding
      and subsequent fusion between the viral and the cellular membrane may require
      interaction with a second receptor.

PMID- 16603525
TI  - Tracing the origin and co-phylogeny of the caliciviruses.
AB  - Caliciviruses infect a wide range of mammalian hosts and include the genus
      Norovirus, the major cause of food-borne viral gastroenteritis in humans. Using
      publicly available sequence data and phylogenetic analysis tools, the origins and
      virus-host co-phylogeny of these viruses were investigated. Here, evidence is
      presented in support of host switching by caliciviruses, but showing that
      zoonotic transfer does not appear to have occurred in the history of these
      viruses. The age or demography of the caliciviruses cannot yet be estimated with
      any firm degree of support, but further studies of this family, as new dated
      sequences become available, could provide key information of importance to human
      health and in understanding the emergence of food-borne disease.

PMID- 16603524
TI  - Arenavirus Z protein as an antiviral target: virus inactivation and protein
      oligomerization by zinc finger-reactive compounds.
AB  - Several disulfide-based and azoic compounds have shown antiviral and virucidal
      properties against arenaviruses in virus yield-inhibition and inactivation
      assays, respectively. The most effective virucidal agent, the aromatic disulfide
      NSC20625, was able to inactivate two strains of the prototype arenavirus species
      Lymphocytic choriomeningitis virus (LCMV). Inactivated viral particles retained
      the biological functions of the virion envelope glycoproteins in virus binding
      and uptake, but were unable to perform viral RNA replication. Furthermore, in
      inactivated virions, the electrophoretic profile of the Z protein was altered
      when analysed under non-reducing conditions, whereas the patterns of the proteins
      NP and GP1 remained unaffected. Treatment of a recombinant LCMV Z protein with
      the virucidal agents induced unfolding and oligomerization of Z to high-molecular
      mass aggregates, probably due to metal-ion ejection and the formation of
      intermolecular disulfide bonds through the cysteine residues of the Z RING
      finger. NSC20625 also exhibited antiviral properties in LCMV-infected cells
      without affecting other cellular RING-motif proteins, such as the promyelocytic
      leukaemia protein PML. Altogether, the investigations described here illustrate
      the potential of the Z protein as a promising target for therapy and the
      prospects of the Z-reactive compounds to prevent arenavirus dissemination.

PMID- 16603526
TI  - Cardiovirus leader proteins are functionally interchangeable and have evolved to
      adapt to virus replication fitness.
AB  - The leader (L) proteins encoded by picornaviruses of the genus Cardiovirus
      [Theiler's murine encephalomyelitis virus (TMEV) and Encephalomyocarditis virus
      (EMCV)] are small proteins thought to exert important functions in virus-host
      interactions. The L protein of persistent TMEV strains was shown to be
      dispensable for virus replication in vitro, but crucial for long-term persistence
      of the virus in the central nervous system of the mouse. The phenotype of
      chimeric viruses generated by exchanging the L-coding regions was analysed and it
      was shown that the L proteins of neurovirulent and persistent TMEV strains are
      functionally interchangeable in vitro and in vivo, despite the fact that L is the
      second most divergent protein encoded by these viruses after the L* protein. The
      L protein encoded by EMCV and Mengo virus (an EMCV strain) shares about 35 %
      amino acid identity with that of TMEV. It differs from the latter by lacking a
      serine/threonine-rich C-terminal domain and by carrying phosphorylated residues
      not conserved in the TMEV L protein. Our data show that, in spite of these
      differences, the L protein of Mengo virus shares, with that of TMEV, the ability
      to inhibit the transcription of type I interferon, cytokine and chemokine genes
      and to interfere with nucleocytoplasmic trafficking of host-cell proteins.
      Interestingly, analysis of viral RNA replication of the recombinant viruses
      raised the hypothesis that L proteins of TMEV and EMCV diverged during evolution
      to adapt to the different replication fitness of these viruses.

PMID- 16603527
TI  - Ebola virus glycoprotein GP is not cytotoxic when expressed constitutively at a
      moderate level.
AB  - Transient expression of Ebola virus (EBOV) glycoprotein GP causes downregulation
      of surface proteins, cell rounding and detachment, a phenomenon believed to play
      a central role in the pathogenicity of the virus. In this study, evidence that
      moderate expression of GP does not result in such morphological changes was
      provided. It was shown that GP continuously produced in 293T cells from the
      Kunjin virus replicon was correctly processed and transported to the plasma
      membrane without affecting the surface expression of beta1 and alpha5 integrins
      and major histocompatibility complex I molecules. The level of GP expression in
      Kunjin replicon GP-expressing cells was similar to that observed in cells
      infected with EBOV early in infection and lower than that produced in cells
      transfected with plasmid DNA, phCMV-GP, expressing GP from a strong promoter.
      Importantly, transient transfection of Kunjin replicon GP-expressing cells with
      GP-coding plasmid DNA resulted in overexpression of GP, which lead to the
      downregulation of surface molecules and massive rounding and detachment of
      transfected cells. Here, it was also demonstrated that cell rounding and
      downregulation of the surface markers are the late events in EBOV infection,
      whereas synthesis and massive release of virus particles occur at early steps and
      do not cause significant cytotoxic effects. These findings indicate that the
      synthesis of EBOV GP in virus-infected cells is controlled well by several
      mechanisms that do not allow GP overexpression and hence the early appearance of
      its cytotoxic properties.

PMID- 16603528
TI  - In vivo antiviral activity: defective interfering virus protects better against
      virulent Influenza A virus than avirulent virus.
AB  - A defective interfering (DI) virus differs from the infectious virus from which
      it originated in having at least one major deletion in its genome. Such DI
      genomes are replicated only in cells infected in trans with homologous infectious
      virus and, as their name implies, they interfere with infectious virus
      replication and reduce the yield of progeny virus. This potent antiviral activity
      has been abundantly demonstrated in cell culture with many different DI animal
      viruses, but few in vivo examples have been reported, with the notable exception
      of DI Influenza A virus. A clue to this general lack of success arose recently
      when an anomaly was discovered in which DI Influenza A virus solidly protected
      mice from lethal disease caused by A/PR/8/34 (H1N1) and A/WSN/40 (H1N1) viruses,
      but protected only marginally from disease caused by A/Japan/305/57 (A/Jap,
      H2N2). The problem was not any incompatibility between the DI and infectious
      genomes, as A/Jap replicated the DI RNA in vivo. However, A/Jap required 300-fold
      more mouse infectious units to cause clinical disease than A/PR8 and it was
      hypothesized that it was this excess of infectivity that abrogated the protective
      activity of the DI virus. This conclusion was verified by varying the proportions
      of DI and challenge virus and showing that increasing the DI virus : infectious
      virus ratio in infected mice resulted in interference. Thus, counter-intuitively,
      DI virus is most effective against viruses that cause disease with low numbers of
      particles, i.e. virulent viruses.

PMID- 16603529
TI  - Protection of mice against Human respiratory syncytial virus by wild-type and
      aglycosyl mouse-human chimaeric IgG antibodies to subgroup-conserved epitopes on
      the G glycoprotein.
AB  - Monoclonal antibodies (mAbs) to conserved epitopes on the G glycoprotein of human
      respiratory syncytial virus (HRSV) subgroup A fail to neutralize the virus in
      cell culture in the absence of complement, but are protective in rodent models of
      infection. They may have potential as prophylactic agents in human infants. In
      order to investigate the role of Fc-dependent pathways in protection by one such
      antibody, 1C2, the V(H) and V(L) genes were isolated by RT-PCR and assembled with
      human kappa light-chain and human gamma1 heavy-chain constant-region genes to
      form two mouse-human chimaeras, which were expressed in NS0 cells. One of the
      chimaeras carried a wild-type gamma1 chain, whilst the other had an aglycosyl
      mutation in the C(H)2 domain rendering the antibody defective in complement
      activation and FcgammaR binding. Whilst both chimaeric antibodies exhibited
      similar avidity for HRSV in ELISA, only the fully glycosylated wild type was
      capable of neutralizing the virus in the presence of complement. In mice
      passively immunized with either murine or wild-type gamma1 chimaeric antibody, no
      virus could be recovered from the lungs 4 days after intranasal inoculation of
      HRSV. In mice immunized with the aglycosyl gamma1 chimaera, however, virus was
      present in the lungs following challenge, although virus titres were
      significantly reduced compared with controls (P < 0.005). These results indicate
      that the protective effect of this antibody is mediated by both Fc-dependent and
      Fc-independent pathways.

PMID- 16603530
TI  - Rotavirus spike protein VP5* binds alpha2beta1 integrin on the cell surface and
      competes with virus for cell binding and infectivity.
AB  - Rotaviruses recognize several cell-surface molecules, including the alpha2beta1
      integrin, and the processes of rotavirus cell attachment and entry appear to be
      multifactorial. The VP5* subunit of the rotavirus spike protein VP4 contains the
      alpha2beta1 ligand sequence Asp-Gly-Glu at residues 308-310. Binding to
      alpha2beta1 and infectivity of monkey rotavirus strain RRV and human rotavirus
      strain Wa, but not porcine rotavirus strain CRW-8, are inhibited by peptides
      containing Asp-Gly-Glu. Asp308 and Gly309 are necessary for the binding of RRV
      VP5* (aa 248-474) to expressed I domain of the alpha2 integrin subunit. Here, the
      ability of RRV VP5* to bind cells and affect rotavirus-integrin interactions was
      determined. Interestingly, VP5* bound to cells at 4 and 37 degrees C, both via
      alpha2beta1 and independently of this integrin. Prior VP5* binding at 37 degrees
      C eliminated RRV binding to cellular alpha2beta1 and reduced RRV and Wa
      infectivity in MA104 cells by 38-46 %. VP5* binding did not affect the
      infectivity of CRW-8. VP5* binding at 4 degrees C did not affect permissive-cell
      infection by RRV, indicating an energy requirement for VP5* competition with
      virus for infectivity. Mutagenesis of VP5* Asp308 and Gly309 eliminated VP5*
      binding to alpha2beta1 and the VP5* inhibition of rotavirus cell binding and
      infection, but not alpha2beta1-independent cell binding by VP5*. These studies
      show for the first time that expressed VP5* binds cell-surface alpha2beta1 using
      Asp308 and Gly309 and inhibits the infection of homologous and heterologous
      rotaviruses that use alpha2beta1 as a receptor.

PMID- 16603532
TI  - In primary human monocyte-derived macrophages exposed to Human immunodeficiency
      virus type 1, does the increased intracellular growth of Leishmania infantum rely
      on its enhanced uptake?
AB  - Concurrent uncontrolled development of human immunodeficiency virus type 1 (HIV
      1) and Leishmania spp. is regarded as an emerging pathogenic combination in
      countries where human beings are exposed to these two micro-organisms. The
      present study was aimed at exploring whether HIV-1 development within a culture
      of human monocyte-derived macrophages (MDMs) affected the further development of
      luciferase-encoding Leishmania infantum using the luciferase activity as a
      readout assay. It was demonstrated that, in cultures of HIV-1-loaded MDMs exposed
      to axenic amastigotes, the luciferase activity was higher than in HIV-1-free
      MDMs. As a preliminary approach to deciphering the possible mechanism through
      which HIV-1 can affect Leishmania infantum, attention was focused on the very
      early processes that could underlie this increased luciferase activity. Using GFP
      labelled parasites, it was possible to establish that, in HIV-1-infected MDMs,
      the percentage of GFP-expressing MDMs was higher (10-20 %) than in cell cultures
      not exposed to HIV-1 (5 %). Two-colour immunofluorescence staining suggested that
      HIV-1 indirectly affects the uptake of parasites inside MDMs. Thus, the observed
      phenomenon seems to be linked with a higher uptake of parasites within MDMs.
      Taken together, the data reported here may contribute to our understanding of
      disseminated Leishmania infection in HIV-1-infected individuals.

PMID- 16603531
TI  - Purifying selection of CCR5-tropic human immunodeficiency virus type 1 variants
      in AIDS subjects that have developed syncytium-inducing, CXCR4-tropic viruses.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection is established by virus
      variants that use the CCR5 co-receptor for entry (CCR5-tropic or R5 variants),
      whereas viruses that use CXCR4 as co-receptor (CXCR4-tropic or X4 variants)
      emerge during disease progression in approximately 50 % of infected subjects. X4
      variants may have a higher fitness ex vivo and their detection is usually
      accompanied by faster T-cell depletion and the onset of AIDS in HIV-1-positive
      individuals. Here, the relationship between the sequence variation of the HIV-1
      env V3-V5 region and positive selective pressure on R5 and X4 variants from
      infected subjects with CD4 T cell counts below 200 cells microl(-1) was studied.
      A correlation was found between genetic distance and CD4(+) cell count at late
      stages of the disease. R5 variants that co-existed with X4 variants were
      significantly less heterogeneous than R5 variants from subjects without X4
      variants (P < 0.0001). Similarly, X4 variants had a significantly higher
      diversity than R5 variants (P < 0.0001), although residues under positive
      selection had a similar distribution pattern in both variants. Therefore, both X4
      and R5 variants were subjected to high selective pressures from the host.
      Furthermore, the interaction between X4 and R5 variants within the same subject
      resulted in a purifying selection on R5 variants, which only survived as a
      homogeneous virus population. These results indicate that R5 variants from X4
      phenotype samples were highly homogeneous and under weakly positive selective
      pressures. In contrast, R5 variants from R5 phenotype samples were highly
      heterogeneous and subject to positive selective pressures.

PMID- 16603533
TI  - Biological characterization of human immunodeficiency virus type 1 subtype C
      protease carrying indinavir drug-resistance mutations.
AB  - Human immunodeficiency virus type 1 subtype C isolates belong to one of the most
      prevalent strains circulating worldwide and are responsible for the majority of
      new infections in the sub-Saharan region and other highly populated areas of the
      globe. In this work, the impact of drug-resistance mutations in the protease gene
      of subtype C viruses was analysed and compared with that of subtype B
      counterparts. A series of recombinant subtype C and B viruses was constructed
      carrying indinavir (IDV)-resistance mutations (M46V, I54V, V82A and L90M) and
      their susceptibility to six FDA-approved protease inhibitor compounds
      (amprenavir, indinavir, lopinavir, ritonavir, saquinavir and nelfinavir) was
      determined. A different impact of these mutations was found when nelfinavir and
      lopinavir were tested. The IDV drug-resistance mutations in the subtype C
      protease backbone were retained for a long period in culture without selective
      pressure when compared with those in subtype B counterparts in washout
      experiments.

PMID- 16603534
TI  - Rapid dissemination of a pathogenic simian/human immunodeficiency virus to
      systemic organs and active replication in lymphoid tissues following intrarectal
      infection.
AB  - A better understanding of virological events during the early phase of human
      immunodeficiency virus 1 (HIV-1) infection is important for development of
      effective antiviral vaccines. In this study, by using quantitative PCR and an
      infectious plaque assay, virus distribution and replication were examined in
      various internal organs of rhesus macaques for almost 1 month after intrarectal
      inoculation of a pathogenic simian immunodeficiency virus/HIV chimeric virus
      (SHIV-C2/1-KS661c). At 3 days post-inoculation (p.i.), proviral DNA was detected
      in the rectum, thymus and axillary lymph node. In lymphoid tissues, infectious
      virus was first detected at 6 days p.i. and a high level of proviral DNA and
      infectious virus were both detected at 13 days p.i. By 27 days p.i., levels of
      infectious virus decreased dramatically, although proviral DNA load remained
      unaltered. In the intestinal tract, levels of infectious virus detected were much
      lower than in lymphoid tissues, whereas proviral DNA was detected at the same
      level as in lymphoid tissues throughout the infection. In the thymus and jejunum,
      CD4CD8 double-positive T cells were depleted earlier than CD4 single-positive
      cells. These results show that the virus spread quickly to systemic tissues after
      mucosal transmission. Thereafter, infectious virus was actively produced in the
      lymphoid tissues, but levels decreased significantly after the peak of viraemia.
      In contrast, in the intestinal tract, infectious virus was produced at low levels
      from the beginning of infection. Moreover, virus pathogenesis differed in CD4
      single-positive and CD4CD8 double-positive T cells.

PMID- 16603535
TI  - Characterization of the murine leukemia virus protease and its comparison with
      the human immunodeficiency virus type 1 protease.
AB  - The protease (PR) of Murine leukemia virus (MLV) was expressed in Escherichia
      coli, purified to homogeneity and characterized by using various assay methods,
      including HPLC-based, photometric and fluorometric activity measurements. The
      specificity of the bacterially expressed PR was similar to that of virion
      extracted PR. Compared with human immunodeficiency virus type 1 (HIV-1) PR, the
      pH optimum of the MLV enzyme was higher. The specificity of the MLV PR was
      further compared with that of HIV-1 PR by using various oligopeptides
      representing naturally occurring cleavage sites in MLV and HIV-1, as well as by
      using bacterially expressed proteins having part of the MLV Gag. Inhibitors
      designed against HIV-1 PR were also active on MLV PR, although all of the tested
      ones were substantially less potent on this enzyme than on HIV-1 PR.
      Nevertheless, amprenavir, the most potent inhibitor against MLV PR, was also able
      to block Gag processing in MLV-infected cells. These results indicate that, in
      spite of the similar function in the life cycle of virus infection, the two PRs
      are only distantly related in their specificity.

PMID- 16603536
TI  - Chimeric peptide vaccine composed of B- and T-cell epitopes of human T-cell
      leukemia virus type 1 induces humoral and cellular immune responses and reduces
      the proviral load in immunized squirrel monkeys (Saimiri sciureus).
AB  - A squirrel monkey model of human T-cell leukemia virus type 1 (HTLV-1) infection
      was used to evaluate the immunogenicity and protective efficacy of a chimeric
      peptide vaccine composed of a B-cell epitope from the envelope region (aa 175
      218) and three HLA-A*0201-restricted cytotoxic T-lymphocyte epitopes derived from
      Tax protein (Tri-Tax). These selected Tax peptides induced secretion of gamma
      interferon (IFN-gamma) in peripheral blood mononuclear cells obtained from
      monkeys chronically infected with HTLV-1. After immunization, a high titre of
      antibodies and a high frequency of IFN-gamma-producing cells were detected
      against the Env and the Tri-Tax immunogens, but not against the individual Tax
      peptides. This might indicate that epitope(s) distinct from those recognized by
      humans are recognized by responder monkeys. After challenge, it was shown by
      competitive PCR that partial protection against HTLV-1 infection could be raised
      in immunized animals. Further studies should be developed to determine the
      duration of this protection.

PMID- 16603538
TI  - Relationship between retroviral vector membrane and vector stability.
AB  - The present work studies the physico-chemical properties of retroviral vector
      membrane, in order to provide some explanation for the inactivation kinetics of
      these vectors and to devise new ways of improving transduction efficiency. For
      this purpose, vectors with an amphotropic envelope produced by TE Fly A7 cells at
      two culture temperatures (37 and 32 degrees C) were characterized by different
      techniques. Electron paramagnetic resonance (EPR) results showed that vectors
      produced at 32 degrees C are more rigid than those produced at 37 degrees C.
      Further characterization of vector membrane composition allowed us to conclude
      that the vector inactivation rate increases with elevated cholesterol to
      phospholipid ratio. Differential scanning calorimetry (DSC) showed that
      production temperature also affects the conformation of the membrane proteins.
      Transduction studies using HCT116 cells and tri-dimensional organ cultures of
      mouse skin showed that vectors produced at 37 degrees C have higher stability and
      thus higher transduction efficiency in gene therapy relevant cells as compared
      with vectors produced at 32 degrees C. Overall, vectors produced at 37 degrees C
      show an increased stability at temperatures below 4 degrees C. Since vector
      membrane physico-chemical properties are affected in response to changes in
      culture temperature, such changes, along with alterations in medium composition,
      can be used prospectively to improve the stability and the transduction
      efficiency of retroviral vectors for therapeutic purposes.

PMID- 16603539
TI  - Movement of potexviruses requires species-specific interactions among the cognate
      triple gene block proteins, as revealed by a trans-complementation assay based on
      the bamboo mosaic virus satellite RNA-mediated expression system.
AB  - The intra- and intercellular transport of potexviruses require interactions among
      viral RNA, coat protein and elements of the triple gene block proteins (TGBps).
      In this study, the requirement of bamboo mosaic virus (BaMV) TGBps for movement
      functions and the compatibilities with those of two potexviruses, Potato virus X
      (PVX) and Foxtail mosaic virus (FoMV), were examined using a satellite RNA
      mediated trans-complementation assay system. Single or multiple TGBps of BaMV,
      PVX and FoMV were expressed from BaMV satellite RNA (satBaMV RNA) vectors to
      complement the functions of green fluorescent protein-tagged, movement-defective
      BaMV with mutation(s) in the matching gene(s). It was found that individual BaMV
      TGBps expressed from the satellite vector could function normally in trans,
      whereas bi-gene BaMV TGBp constructs in which the expression of TGBp3 might be
      impaired and individual TGBp genes from PVX or FoMV could not complement the
      movement functions of the defective helper viruses. Furthermore, alterations of
      the ratio among TGBps by ectopic expression of individual components of TGBps
      from satBaMV RNA vectors did not affect the cell-to-cell movement capabilities of
      wild-type BaMV significantly. The results indicate that species-specific
      interactions among movement proteins are obligatory for the cell-to-cell movement
      of BaMV and possibly other potexviruses.

PMID- 16603540
TI  - Emergence of a resistance-breaking isolate of Rice yellow mottle virus during
      serial inoculations is due to a single substitution in the genome-linked viral
      protein VPg.
AB  - The recessive gene rymv-1, responsible for the high resistance of Oryza sativa
      'Gigante' to Rice yellow mottle virus (genus Sobemovirus), was overcome by the
      variant CI4*, which emerged after serial inoculations of the non-resistance
      breaking (nRB) isolate CI4. By comparison of the full-length sequences of CI4 and
      CI4*, a non-synonymous mutation was identified at position 1729, localized in the
      putative VPg domain, and an assay was developed based on this single-nucleotide
      polymorphism. The mutation G1729T was detected as early as the first passage in
      resistant plants and was found in all subsequent passages. Neither reversion nor
      any additional mutation was observed. The substitution G1729T, introduced by
      mutagenesis into the VPg of an nRB infectious clone, was sufficient to induce
      symptoms in uninoculated leaves of O. sativa 'Gigante'. This is the first
      evidence that VPg is a virulence factor in plants with recessive resistance
      against viruses outside the family Potyviridae.

PMID- 16603541
TI  - Micromonas pusilla reovirus: a new member of the family Reoviridae assigned to a
      novel proposed genus (Mimoreovirus).
AB  - Micromonas pusilla reovirus (MpRV) is an 11-segmented, double-stranded RNA virus
      isolated from the marine protist Micromonas pusilla. Sequence analysis (including
      conserved termini and presence of core motifs of reovirus polymerase), morphology
      and physicochemical properties confirmed the status of MpRV as a member of the
      family Reoviridae. Electron microscopy showed that intact virus particles are
      unusually larger (90-95 nm) than the known size of particles of viruses belonging
      to the family Reoviridae. Particles that were purified on caesium chloride
      gradients had a mean size of 75 nm (a size similar to the size of intact
      particles of members of the family Reoviridae), indicating that they lost outer
      coat components. The subcore particles had a mean size of 50 nm and a smooth
      surface, indicating that MpRV belongs to the non-turreted Reoviridae. The maximum
      amino acid identity with other reovirus proteins was 21 %, which is compatible
      with values existing between distinct genera. Based on morphological and sequence
      findings, this virus should be classified as the representative of a novel genus
      within the family Reoviridae, designated Mimoreovirus (from Micromonas pusilla
      reovirus). The topology of the phylogenetic tree built with putative polymerase
      sequences of the family Reoviridae suggested that the branch of MpRV could be
      ancestral. Further analysis showed that segment 1 of MpRV was much longer (5792
      bp) than any other reovirus segment and encoded a protein of 200 kDa (VP1). This
      protein exhibited significant similarities to O-glycosylated proteins, including
      viral envelope proteins, and is likely to represent the additional outer coat of
      MpRV.

PMID- 16603542
TI  - Acid inactivation of prions: efficient at elevated temperature or high acid
      concentration.
AB  - Scrapie prion rods isolated from hamster and non-infectious aggregates of the
      corresponding recombinant protein rPrP(90-231) were incubated with hydrochloric
      acid. The amount of PrP and of infectivity that survived incubation in HCl at
      varying times, acid concentrations and temperatures was quantified by Western
      blot densitometry and bioassays, respectively. Prion rods and rPrP aggregates
      showed similar HCl hydrolysis kinetics of PrP, indicating structural homology.
      For 1 M HCl and 25 degrees C, the rate of PrP hydrolysis follows first-order
      kinetics at 0.014 h(-1); the rate of infectivity inactivation is 0.54 h(-1).
      Hydrolysis for 1 h at 25 degrees C was only slightly proportional to HCl
      concentration up to 5 M, but complete loss of infectivity and PrP reduction to <2
      % was observed at 8 M HCl. The temperature dependence of unhydrolysed PrP, as
      well as infectivity at 1 M HCl for 1 h, showed a slight decrease up to 45 degrees
      C, but a sigmoidal decrease by several orders of magnitude at higher
      temperatures. The slow hydrolysis of PrP and inactivation of infectivity by acid
      treatment at room temperature are attributed to solvent inaccessibility of prion
      rods and rPrP aggregates, respectively. The more effective hydrolysis and
      inactivation at temperatures above 45 degrees C are interpreted as thermally
      induced disaggregation with an activation energy of 50-60 kJ mol(-1). Most
      importantly, infectivity was always inactivated faster or to a higher extent than
      PrP was hydrolysed at several incubation times, HCl concentrations and
      temperatures.

PMID- 16603537
TI  - Genome-wide mapping of foamy virus vector integrations into a human cell line.
AB  - Integration-site selection by retroviruses and retroviral vectors has gained
      increased scientific interest. Foamy viruses (FVs) constitute a unique subfamily
      (Spumavirinae) of the family Retroviridae, for which the integration pattern into
      the human genome has not yet been determined. To accomplish this, 293 cells were
      transduced with FV vectors and the integration sites into the cellular genome
      were determined by a high-throughput method based on inverse PCR. For comparison,
      a limited number of murine leukemia virus (MLV) and human immunodeficiency virus
      (HIV) integration sites were analysed in parallel. Altogether, 628 FV, 87 HIV and
      141 MLV distinct integration sites were mapped to the human genome. The sequences
      were analysed for RefSeq genes, promoter regions, CpG islands and insertions into
      cellular oncogenes. Compared with the integration-site preferences of HIV, which
      strongly favours active genes, and MLV, which favours integration near
      transcription-start regions, our results indicate that FV integration has neither
      of these preferences. However, once integration has occurred into a transcribed
      region of the genome, FVs tend to target promoter-close regions, albeit with less
      preference than MLV. Furthermore, our study revealed a palindromic consensus
      sequence for integration, which was centred on the virus-specific, four-base
      duplicated target site. In summary, it is shown that the integration pattern of
      FVs appears to be unique compared with those of other retroviral genera.

PMID- 16603543
TI  - Identification of an allelic variant of the goat PrP gene associated with
      resistance to scrapie.
AB  - The association between PrP gene variations and scrapie susceptibility was
      studied in a single herd of Ionica breed goats. The entire herd comprised 100
      animals, 11 of which were clinically affected and showed pathological prion
      protein (PrP(Sc)) deposition in both their central nervous system (CNS) and
      lymphoreticular system (LRS). Among asymptomatic goats, nine harboured PrP(Sc) in
      both CNS and LRS, 19 showed PrP(Sc) only at the LRS level and 61 animals had no
      PrP(Sc) deposition. Genetic analysis of the PrP gene coding sequence revealed the
      presence of several polymorphisms, namely G37V, T110P, H143R, R154H, Q222K and
      P240S. Silent polymorphisms were also found at codons 42, 138, 219 and 232. The
      effect of PrP polymorphism on scrapie susceptibility was assessed by comparing
      the genotype distribution at each locus among animals with different pathogenetic
      and clinical disease stages. Significant differences in the distribution of
      genotypes were observed for codons 154 and 222, with polymorphism at codon 154
      modulating susceptibility to scrapie and lysine at codon 222 being associated
      with scrapie resistance. The allelic variant encoding lysine at position 222
      could be a valuable candidate to select in the framework of appropriate breeding
      programmes for scrapie resistance in goats.

PMID- 16603544
TI  - NMR structure of the full-length linear dimer of stem-loop-1 RNA in the HIV-1
      dimer initiation site.
AB  - The packaging signal of HIV-1 RNA contains a stem-loop structure, SL1, which
      serves as the dimerization initiation site for two identical copies of the genome
      and is important for packaging of the RNA genome into the budding virion and for
      overall infectivity. SL1 spontaneously dimerizes via a palindromic hexanucleotide
      sequence in its apical loop, forming a metastable kissing dimer form. Incubation
      with nucleocapsid protein causes this form to refold to a thermodynamically
      stable mature linear dimer. Here, we present an NMR structure of the latter form
      of the full-length SL1 sequence of the Lai HIV-1 isolate. The structure was
      refined using nuclear Overhauser effect and residual dipolar coupling data. The
      structure presents a symmetric homodimer of two RNA strands of 35 nucleotides
      each; it includes five stems separated by four internal loops. The central
      palindromic stem is surrounded by two symmetric adenine-rich 1-2 internal loops,
      A-bulges. All three adenines in each A-bulge are stacked inside the helix,
      consistent with the solution structures of shorter SL1 constructs determined
      previously. The outer 4-base pair stems and, proximal to them, purine-rich 1-3
      internal loops, or G-bulges, are the least stable parts of the molecule. The G
      bulges display high conformational variability in the refined ensemble of
      structures, despite the availability of many structural restraints for this
      region. Nevertheless, most conformations share a similar structural motif: a
      guanine and an adenine from opposite strands form a GA mismatch stacked on the
      top of the neighboring stem. The two remaining guanines are exposed, one in the
      minor groove and another in the major groove side of the helix, consistent with
      secondary structure probing data for SL1. These guanines may be recognized by the
      nucleocapsid protein, which binds tightly to the G-bulge in vitro.

PMID- 16603545
TI  - Binding of a single Rb+ increases Na+/K+-ATPase, activating dephosphorylation
      without stoichiometric occlusion.
AB  - We used partially purified Na+/K+-ATPase from pig kidney to study
      dephosphorylation, occlusion, and ATPase activity in the same enzyme preparation
      and in media of identical composition containing 10 microM ATP and different
      concentrations of Rb+, used as a K+ congener. The experiments were performed
      using a rapid-mixing apparatus with a time resolution of 3.5 ms. The main
      findings were as follows. (i) At sufficiently low Rb+ concentration the initial
      rate of dephosphorylation was higher than that of occlusion, (ii) as [Rb+] tended
      to zero the slope of the time course of occlusion but not that of the time course
      of dephosphorylation approached zero and, (iii) as Rb+ concentration increased,
      ATPase activity first increased and, after passing through a maximum, tended to a
      value that was lower than that observed in media without Rb+. None of these
      results is compatible with the currently held idea that binding of a single Rb+
      to the E2P conformer of the ATPase does not modify the rate of dephosphorylation
      and strongly suggest that a single Rb+ does promote dephosphorylation through a
      mechanism that is not stoichiometrically coupled to Rb+ occlusion. If this
      mechanism is included in the currently accepted scheme for ATP hydrolysis by the
      Na+/K+-ATPase, a reasonable prediction of the experimental results is obtained.

PMID- 16603546
TI  - Reversible membrane interaction of BAD requires two C-terminal lipid binding
      domains in conjunction with 14-3-3 protein binding.
AB  - BAD is a Bcl-2 homology domain 3 (BH3)-only proapoptotic member of the Bcl-2
      protein family that is regulated by phosphorylation in response to survival
      factors. Binding of BAD to mitochondria is thought to be exclusively mediated by
      its BH3 domain. We show here that BAD binds to lipids with high affinities,
      predominantly to negatively charged phospholipids, such as phosphatidylserine,
      phosphatidic acid, and cardiolipin, as well as to cholesterol-rich liposomes. Two
      lipid binding domains (LBD1 and LBD2) with different binding preferences were
      identified, both located in the C-terminal part of the BAD protein. BAD
      facilitates membrane translocation of Bcl-XL in a process that requires LBD2.
      Integrity of LBD1 and LBD2 is also required for proapoptotic activity in vivo.
      Phosphorylation of BAD does not affect membrane binding but renders BAD
      susceptible to membrane extraction by 14-3-3 proteins. BAD can be removed
      efficiently by 14-3-3zeta, -eta, -tau and lesxs efficiently by other 14-3-3
      isoforms. The assembled BAD.14-3-3 complex exhibited high affinity for
      cholesterol-rich liposomes but low affinity for mitochondrial membranes. We
      conclude that BAD is a membrane-associated protein that has the hallmarks of a
      receptor rather than a ligand. Lipid binding is essential for the proapoptotic
      function of BAD in vivo. The data support a model in which BAD shuttles in a
      phosphorylation-dependent manner between mitochondria and other membranes and
      where 14-3-3 is a key regulator of this relocation. The dynamic interaction of
      BAD with membranes is tied to activation and membrane translocation of Bcl-XL.

PMID- 16603547
TI  - The presenilin-2 loop peptide perturbs intracellular Ca2+ homeostasis and
      accelerates apoptosis.
AB  - In cells undergoing apoptosis, a 22-amino-acid presenilin-2-loop peptide (PS2-LP,
      amino acids 308-329 in presenilin-2) is generated through cleavage of the
      carboxyl-terminal fragment of presenilin-2 by caspase-3. The impact of PS2-LP on
      the progression of apoptosis, however, is not known. Here we show that PS2-LP is
      a potent inducer of the mitochondrial-dependent cell death pathway when
      transduced as a fusion protein with HIV-TAT. Biochemical and functional studies
      demonstrate that TAT-PS2-LP can interact with the inositol 1,4,5-trisphosphate
      receptor and activate Ca(2+) release from the endoplasmic reticulum. These
      results indicate that PS2-LP-mediated alteration of intracellular Ca(2+)
      homeostasis may be linked to the acceleration of apoptosis. Therefore, targeting
      the function of PS2-LP could provide a useful therapeutic tool for the treatment
      of cancer and degenerative diseases.

PMID- 16603548
TI  - Contribution of amino acid side chains to sugar binding specificity in a
      galactokinase, Gal1p, and a transcriptional inducer, Gal3p.
AB  - The crystal structure of the yeast galactokinase, Gal1p, in the presence of its
      substrates has been solved recently. We systematically mutated each of the amino
      acid side chains that, from the structure, are implicated to be involved in
      direct contact with the hydroxyl groups of the galactose ring. One of these
      mutations, D62A, abolished all detectable galactokinase activity but retained the
      ability to use d-glucose as a substrate. Mutation of Asp-62 to either leucine,
      phenylalanine, or histidine resulted in the formation of protein with similar
      characteristics to D62A. Yeast galactokinase is highly similar to Gal3p, the
      ligand sensor and transcriptional inducer of the GAL genes. Equivalent mutations
      in Gal3p also abolished its ability to respond to galactose and uncovered its
      ability to respond to d-glucose. It therefore appears that Gal1p and Gal3p
      respond to their substrates in a similar, perhaps identical, fashion. This work
      also validates the approach of screening for mutants in an easily assayable
      system prior to mutant analysis in a more experimentally difficult
      transcriptional regulator.

PMID- 16603549
TI  - Intracellular actions of group IIA secreted phospholipase A2 and group IVA
      cytosolic phospholipase A2 contribute to arachidonic acid release and
      prostaglandin production in rat gastric mucosal cells and transfected human
      embryonic kidney cells.
AB  - Gastric epithelial cells liberate prostaglandin E(2) in response to cytokines as
      part of the process of healing of gastric lesions. Treatment of the rat gastric
      epithelial cell line RGM1 with transforming growth factor-alpha and interleukin
      1beta leads to synergistic release of arachidonate and production of
      prostaglandin E(2). Results with highly specific and potent phospholipase A(2)
      inhibitors and with small interfering RNA show that cytosolic phospholipase A(2)
      alpha and group IIA secreted phospholipase A(2) contribute to arachidonate
      release from cytokine-stimulated RGM1 cells. In the late phase of arachidonate
      release, group IIA secreted phospholipase A(2) is induced (detected at the mRNA
      and protein levels), and the action of cytosolic phospholipase A(2)-alpha is
      required for this induction. Results with RGM1 cells and group IIA secreted
      phospholipase A(2)-transfected HEK293 cells show that the group IIA phospholipase
      acts prior to externalization from the cells. RGM1 cells also express group XIIA
      secreted phospholipase A(2), but this enzyme is not regulated by cytokines nor
      does it contribute to arachidonate release. The other eight secreted
      phospholipases A(2) were not detected in RGM1 cells at the mRNA level. These
      results clearly show that cytosolic and group IIA secreted phospholipases A(2)
      work together to liberate arachidonate from RGM1 cell phospholipids in response
      to cytokines.

PMID- 16603550
TI  - On-farm eradication of foot-and-mouth disease as an alternative to mass culling.
AB  - A control and eradication programme for foot-and-mouth disease (FMD) was
      initiated on a 1500-sow farm in Asia as an alternative to mass culling. The
      programme was based on mass vaccination and exposure to FMD virus to ensure the
      development of effective immunity throughout the population. Pigs are not long
      term carriers of FMD virus and it should be eliminated by 21 days after
      infection. Entry of breeding stock was temporarily halted and the sow herd was
      partially depopulated in order to create a buffer between the infected and
      uninfected animals. After exposure to the virus and partial depopulation, the
      virus was eliminated through unidirectional pig flow and strict all-in/all-out
      procedures, and by thorough cleaning and disinfection of the buildings. Twelve
      months after the initial outbreak, the eradication plan was completed and
      successful. In parallel with the eradication programme, a small-scale isolated
      weaning project was carried out with the sow population that was moved out of the
      affected farm; 708 piglets were weaned to a separate facility 300 m away. No
      clinical signs of FMD were observed and the piglets remained serologically
      negative.

PMID- 16603551
TI  - Seasonal variations in the developmental competence of bovine oocytes matured in
      vitro.
AB  - Ovaries were collected over a period of two years from heifers slaughtered at
      under 30 months of age and used to harvest 1757 oocytes. After in vitro
      maturation, fertilisation and culture, the proportions of oocytes and cleaved
      embryos that developed to blastocysts were significantly higher (P<0.01) in the
      autumn, from September to November, than in the spring, from March to May. In
      contrast, embryo development, as assessed by oocytes that developed to eight or
      more cells and blastocysts, was lowest (P<0.01) in the spring. These results were
      consistent during the two-year study, indicating a seasonal fluctuation in oocyte
      competence.

PMID- 16603552
TI  - Randomised, placebo-controlled trial of a live vaccine against porcine
      reproductive and respiratory syndrome virus in sows on infected farms.
AB  - A randomised, double-blinded, placebo-controlled study into the effectiveness and
      safety of a vaccine against porcine reproductive and respiratory syndrome virus
      (PRRSV) was carried out on three farms with a history compatible with chronic
      PRRSV infection; representative groups of sows and gilts were injected with a
      live vaccine against PRRSV, and during the next six weeks no side effects were
      observed. The remaining sows and gilts on the three farms were then vaccinated
      with the same vaccine. Again, no side effects were observed. There were
      significant reductions in abortion, reproductive disease, returns to oestrus and
      the numbers of stillborn pigs per sow, and significant increases in the numbers
      of liveborn pigs per sow and weaned pigs per sow among the vaccinated animals.

PMID- 16603553
TI  - Haematological and serum biochemical values of southern chamois (Rupicapra
      pyrenaica).
AB  - Blood samples were taken from 75 free-ranging southern chamois (Rupicapra
      pyrenaica) captured in drive-nets in Catalonia, north-eastern Spain, and 20
      haematological and 24 serum biochemical variables were analysed. The values were
      similar to those of other species of the Caprinae subfamily, except for cortisol,
      the concentration of which was higher. The red blood cell count (RBC), platelets
      and leucocytes, and the concentrations of cortisol, lactate, muscular enzymes and
      gamma-globulins were higher in summer than in spring, whereas the mean
      corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin
      concentration, and the concentrations of cholesterol, total bilirubin and
      creatinine were lower. Adult males had higher RBCs and haemoglobin values than
      females in summer, and lower leucocyte, lymphocyte and neutrophil counts than
      females and yearling males. The concentrations of triglycerides, total bilirubin,
      lactate, creatinine, urea, chloride and alpha2-globulins were higher in adult
      males than yearling males. In summer the adult females had higher values for
      platelets, lymphocytes, cortisol, sodium and muscular enzymes.

PMID- 16603554
TI  - Anthelmintic activity of Leucaena leucocephala seed extract on Haemonchus
      contortus-infective larvae.

PMID- 16603555
TI  - Oestrogen receptors in a case of hydrometra in a bitch.

PMID- 16603556
TI  - Bovine tuberculosis in cats.

PMID- 16603557
TI  - Locums and self-employment.

PMID- 16603558
TI  - Maintenance of anaesthesia in practice.

PMID- 16603559
TI  - Highly pathogenic avian influenza H5N1 subtype in mute swans in Italy.

PMID- 16603560
TI  - Tail end.

PMID- 16603562
TI  - Practice standards scheme and farm practices.

PMID- 16603563
TI  - Grape toxicity in dogs.

PMID- 16603564
TI  - Bone-patellar tendon-bone autografts versus hamstring autografts for
      reconstruction of anterior cruciate ligament: meta-analysis.
AB  - OBJECTIVES: To compare bone-patellar tendon-bone autografts with hamstring
      autografts for reconstruction of the anterior cruciate ligament. DATA SOURCES:
      Medline, WebSPIRS, Science Citation Index, Current Contents databases, and
      Cochrane Central Register of Controlled Trials. Review methods All randomised
      controlled trials reporting one or more outcome related to stability
      (instrumented measurement of knee laxity, Lachman test, or pivot shift test) and
      morbidity (anterior knee pain, kneeling test, loss of extension, or graft
      failure). Study quality was assessed by using a 5 point scale. Random effect
      models were used to pool the data. Heterogeneity in the effect of treatment was
      tested on the basis of study quality, randomisation status, and number of tendon
      strands used. RESULTS: 24 trials of 18 cohorts (1512 patients) met the inclusion
      criteria. Study quality was poor for nine studies and fair for nine studies. The
      weighted mean difference of the instrumented measurement of knee laxity was 0.36
      (95% confidence interval 0.01 to 0.71; P = 0.04). Relative risk of a positive
      Lachman test was 1.22 (1.01 to 1.47; P = 0.04), of anterior knee pain 0.57 (0.44
      to 0.74; P < 0.0001), of a positive kneeling test 0.26 (0.14 to 0.48; P <
      0.0001), and of loss of extension 0.52 (0.34 to 0.80; P = 0.003). Other results
      were not significant. CONCLUSION: Morbidity was lower for hamstring autografts
      than for patellar tendon autografts. Evidence that patellar tendon autografts
      offer better stability was weak. The poor quality of the studies calls into
      question the robustness of the analyses.

PMID- 16603566
TI  - Gene therapy and uterine leiomyoma: a review.
AB  - Leiomyomas (fibroids) are common estrogen-dependent uterine tumours that cause
      significant morbidity for women and a substantial economic impact on health
      delivery systems. Currently, there is no effective medical treatment option for
      this condition-hysterectomy is the mainstay of management. This is not an
      attractive choice for many women, especially patients desiring to preserve their
      fertility potential. Gene therapy is becoming a clinical reality, with more than
      600 clinical trials worldwide. Researchers have recently attempted to develop a
      gene-therapy-based approach for the ablation of uterine fibroids. The localized
      nature of this condition and its accessibility using different imaging or
      endoscopic techniques make it an attractive target for direct delivery of gene
      based vectors. Recent work from our laboratory suggests the potential use of a
      dominant-negative form of estrogen receptor (ER) to inactivate estrogen
      signalling in leiomyoma cells and induce apoptosis. Our in vivo data in a mouse
      model demonstrate the ability of an adenovirus-expressing dominant-negative ER to
      arrest leiomyoma growth. We and others also have described the utility of the
      herpes simplex virus-thymidine kinase (HSV-TK) plus ganciclovir (GCV) suicide
      gene-therapy system to effectively eradicate leiomyoma cells by utilizing the
      bystandard effect phenomena and the high expression of gap-junction protein in
      these tumours. Further work on rat models will pave the way for future leiomyoma
      gene-therapy clinical trials and allow the realization of gene therapy as a
      viable non-surgical option for this common problem in women's health.

PMID- 16603565
TI  - Active and passive smoking and development of glucose intolerance among young
      adults in a prospective cohort: CARDIA study.
AB  - OBJECTIVE: To assess whether active and passive smokers are more likely than non
      smokers to develop clinically relevant glucose intolerance or diabetes. DESIGN:
      Coronary artery risk development in young adults (CARDIA) is a prospective cohort
      study begun in 1985-6 with 15 years of follow-up. SETTING: Participants recruited
      from Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland,
      California, USA. PARTICIPANTS: Black and white men and women aged 18-30 years
      with no glucose intolerance at baseline, including 1386 current smokers, 621
      previous smokers, 1452 never smokers with reported exposure to secondhand smoke
      (validated by serum cotinine concentrations 1-15 ng/ml), and 1113 never smokers
      with no exposure to secondhand smoke. MAIN OUTCOME MEASURE: Time to development
      of glucose intolerance (glucose > or = 100 mg/dl or taking antidiabetic drugs)
      during 15 years of follow-up. RESULTS: Median age at baseline was 25, 55% of
      participants were women, and 50% were African-American. During follow-up, 16.7%
      of participants developed glucose intolerance. A graded association existed
      between smoking exposure and the development of glucose intolerance. The 15 year
      incidence of glucose intolerance was highest among smokers (21.8%), followed by
      never smokers with passive smoke exposure (17.2%), and then previous smokers
      (14.4%); it was lowest for never smokers with no passive smoke exposure (11.5%).
      Current smokers (hazard ratio 1.65, 95% confidence interval 1.27 to 2.13) and
      never smokers with passive smoke exposure (1.35, 1.06 to 1.71) remained at higher
      risk than never smokers without passive smoke exposure after adjustment for
      multiple baseline sociodemographic, biological, and behavioural factors, but risk
      in previous smokers was similar to that in never smokers without passive smoke
      exposure. CONCLUSION: These findings support a role of both active and passive
      smoking in the development of glucose intolerance in young adulthood.

PMID- 16603567
TI  - Genomic analyses facilitate identification of receptors and signalling pathways
      for growth differentiation factor 9 and related orphan bone morphogenetic
      protein/growth differentiation factor ligands.
AB  - Recent advances in genomic sequencing allow a new paradigm in hormonal research,
      and a comparative genomic approach facilitates the identification of receptors
      and signalling mechanisms for orphan ligands of the transforming growth factor
      beta (TGFbeta) superfamily. Instead of purifying growth differentiation factor 9
      (GDF9) receptor proteins for identification, we hypothesized that GDF9, like
      other ligands in the TGFbeta family, activates type II and type I
      serine/threonine kinase receptors. Because searches of the human genome for genes
      with sequence homology to known serine/threonine kinase receptors failed to
      reveal uncharacterized receptor genes, GDF9 likely interacts with the known type
      II and type I activin receptor-like kinase (ALK) receptors in granulosa cells. We
      found that co-treatment with the bone morphogenetic protein (BMP) type II
      receptor (BMPRII) ectodomain blocks GDF9 activity. Likewise, in a GDF9-non
      responsive cell line, overexpression of ALK5, but none of the other six type I
      receptors, conferred GDF9 responsiveness. The roles of BMPRII and ALK5 as
      receptors for GDF9 were validated in granulosa cells using gene "knock-down"
      approaches. Furthermore, we demonstrated the roles of BMPRII, ALK3 and ALK6 as
      the receptors for the orphan ligands GDF6, GDF7 and BMP10. Thus, evolutionary
      tracing of polypeptide ligands, receptors and downstream signalling molecules in
      their respective 'subgenomes' facilitates a new approach for hormonal research.

PMID- 16603568
TI  - Teachers' perceptions of health education practice in Northern Ireland: reported
      differences between policy and non-policy holding schools.
AB  - It is generally accepted that schools should devote resources to developing and
      disseminating a health education policy, yet there is little empirical evidence
      to establish the value of policy in this context. This study examined teachers'
      perceptions of health education practice in policy and non-policy holding
      schools. A questionnaire measuring aspects of health education practice was
      issued to a random sample of schools. This consisted of 276 primary and 119 post
      primary schools. In this cross-sectional study, significant differences in
      teachers' evaluations were found between policy and non-policy holding schools.
      It was evident that the presence of a health education policy was associated with
      higher ratings of health education practice. This evidence suggests that policy
      has intrinsic value in terms of health education practice. The development and
      dissemination of policy documents were also examined to assess the workload
      involved.

PMID- 16603569
TI  - Choosing indicators to evaluate Healthy Cities projects: a political task?
AB  - Ever since their beginning in 1986, Healthy Cities projects all over the world
      have been confronted with the issue of evaluation. However, after 20 years, many
      key dilemmas constantly reappear, people often looking for a kind of 'magic' list
      of universally applicable indicators to evaluate these initiatives. In this
      article we address five questions, allowing to illustrate the evaluative dilemmas
      the Healthy Communities movement is confronted with: Why evaluate Healthy Cities?
      What should be evaluated? Evaluate for who? Who should undertake the evaluation?
      How should the evaluation be performed? We conclude by formulating three
      recommendations in order to stimulate exchanges and debate. Our argument is based
      on a recent thorough analysis of the evaluative literature pertaining to the
      Healthy Cities movement, as well as on two decades of reflection on and
      involvement with this issue locally, nationally and internationally.

PMID- 16603570
TI  - Evaluating the effectiveness of health promotion policy: changes in the law on
      drinking and driving in California.
AB  - The purpose of the study was to determine the utility of general population
      health surveillance data for evaluating broad policy changes that relate to
      health promotion. Data were drawn from the United States (US) Behavioral Risk
      Factor Surveillance System (BRFSS) for one US state, California. Because these
      data are collected frequently and continually, a quasi-experimental approach to
      the evaluation was possible using a type of interrupted time series analysis or
      longitudinal impact analysis. A statistically significant decrease in the number
      of declared episodes of drinking and driving was found after enactment of new
      state policy. These findings were compared and found consistent with another
      study in California that examined the effect of changes in the law on alcohol
      related traffic accidents. Our findings suggest that data from a behavioral
      surveillance system, in this case the BRFSS, are useful to evaluate the effect of
      a health promotion intervention. Further, the study demonstrates the utility of
      comparing different data sources when assessing a population-wide change in
      health promotion policy.

PMID- 16603571
TI  - Patterns of disease among adults hospitalized with dengue infections.
AB  - BACKGROUND: Recent years have seen an increase in dengue infections among adults
      in Sri Lanka, with similar trends seen in many other countries. Data on the
      natural history and outcome of dengue in adults are quite limited. AIM: To study
      clinical and laboratory findings in adult dengue patients hospitalized in Sri
      Lanka during a recent major dengue epidemic. DESIGN: Prospective observational
      study. METHODS: Clinical, laboratory and demographic information were collected
      from adult patients with confirmed dengue infections (n = 108) treated in a
      general medical ward in Sri Lanka from 24 April to 31 July 2004. RESULTS: There
      were 68 male and 40 female patients, mean age 26.6 years. Dengue fever (DF) was
      seen in 33 (30.6%) and dengue haemorrhagic fever (DHF) in 75 (69.4%). Of the 37
      (34.3%) with primary dengue infections, 19 (51.4%) developed DF and 18 (48.6%)
      developed DHF. Overall, 42 patients (38.9%) had bleeding manifestations. These
      adults showed differences in clinical and laboratory findings, disease severity
      and mortality, compared to children seen during the same epidemic. Secondary
      dengue infections were significantly associated with development of severe
      disease (OR 5.0, 95%CI 1.9-13.5, p < 0.001). Mortality was 3.7%. DISCUSSION:
      Pooling data on adult dengue patients from different regions should help us to
      understand the natural history of disease in this group. It would also help in
      developing evidence-based treatment guidelines and allocating limited and scarce
      health resources. Our data contribute towards this goal.

PMID- 16603572
TI  - Successful treatment of calciphylaxis with cinacalcet-an alternative to
      parathyroidectomy?

PMID- 16603573
TI  - Identification and stoichiometry of glycosylphosphatidylinositol-anchored
      membrane proteins of the human malaria parasite Plasmodium falciparum.
AB  - Most proteins that coat the surface of the extracellular forms of the human
      malaria parasite Plasmodium falciparum are attached to the plasma membrane via
      glycosylphosphatidylinositol (GPI) anchors. These proteins are exposed to
      neutralizing antibodies, and several are advanced vaccine candidates. To identify
      the GPI-anchored proteome of P. falciparum we used a combination of proteomic and
      computational approaches. Focusing on the clinically relevant blood stage of the
      life cycle, proteomic analysis of proteins labeled with radioactive glucosamine
      identified GPI anchoring on 11 proteins (merozoite surface protein (MSP)-1, -2, 
      4, -5, -10, rhoptry-associated membrane antigen, apical sushi protein, Pf92,
      Pf38, Pf12, and Pf34). These proteins represent approximately 94% of the GPI
      anchored schizont/merozoite proteome and constitute by far the largest validated
      set of GPI-anchored proteins in this organism. Moreover MSP-1 and MSP-2 were
      present in similar copy number, and we estimated that together these proteins
      comprise approximately two-thirds of the total membrane-associated surface coat.
      This is the first time the stoichiometry of MSPs has been examined. We observed
      that available software performed poorly in predicting GPI anchoring on P.
      falciparum proteins where such modification had been validated by proteomics.
      Therefore, we developed a hidden Markov model (GPI-HMM) trained on P. falciparum
      sequences and used this to rank all proteins encoded in the completed P.
      falciparum genome according to their likelihood of being GPI-anchored. GPI-HMM
      predicted GPI modification on all validated proteins, on several known membrane
      proteins, and on a number of novel, presumably surface, proteins expressed in the
      blood, insect, and/or pre-erythrocytic stages of the life cycle. Together this
      work identified 11 and predicted a further 19 GPI-anchored proteins in P.
      falciparum.

PMID- 16603574
TI  - Identification of proteomic signatures of exposure to marine pollutants in
      mussels (Mytilus edulis).
AB  - Bivalves and especially mussels are very good indicators of marine and estuarine
      pollution, and so they have been widely used in biomonitoring programs all around
      the world. However, traditional single parameter biomarkers face the problem of
      high sensitivity to biotic and abiotic factors. In our study, digestive gland
      peroxisome-enriched fractions of Mytilus edulis (L., 1758) were analyzed by DIGE
      and MS. We identified several proteomic signatures associated with the exposure
      to several marine pollutants (diallyl phthalate, PBDE-47, and bisphenol-A).
      Animals collected from North Atlantic Sea were exposed to the contaminants
      independently under controlled laboratory conditions. One hundred and eleven
      spots showed a significant increase or decrease in protein abundance in the two
      dimensional electrophoresis maps from the groups exposed to pollutants. We
      obtained a unique protein expression signature of exposure to each of those
      chemical compounds. Moreover a set of proteins composed a proteomic signature in
      common to the three independent exposures. It is remarkable that the principal
      component analysis of these spots showed a discernible separation between groups,
      and so did the hierarchical clustering into four classes. The 14 proteins
      identified by MS participate in alpha- and beta-oxidation pathways, xenobiotic
      and amino acid metabolism, cell signaling, oxyradical metabolism, peroxisomal
      assembly, respiration, and the cytoskeleton. Our results suggest that proteomic
      signatures could become a valuable tool to monitor the presence of pollutants in
      field experiments where a mixture of pollutants is often present. Further studies
      on the identified proteins could provide crucial information to understand
      possible mechanisms of toxicity of single xenobiotics or mixtures of them in
      marine ecosystems.

PMID- 16603575
TI  - Risk assessment in acute pulmonary embolism.

PMID- 16603576
TI  - Incidence of recognized and unrecognized myocardial infarction in men and women
      aged 55 and older: the Rotterdam Study.

PMID- 16603577
TI  - Clinical and cost-effectiveness of left ventricular assist devices as a bridge to
      heart transplantation for people with end-stage heart failure: a systematic
      review and economic evaluation.
AB  - AIMS: To evaluate the clinical and cost-effectiveness of left ventricular (LV)
      assist devices (LVADs) as a bridge to transplant (BTT) for people with end-stage
      heart failure (ESHF) through a systematic review and economic evaluation. METHODS
      AND RESULTS: The systematic review and economic evaluation was conducted
      according to internationally recognized methods. The search strategy identified
      systematic reviews, randomized controlled trials, quasi-experimental studies, and
      observational studies evaluating the effects of LVADs on survival, functional
      capacity, and quality of life. Cost-effectiveness was assessed through a 5-year
      decision analytic model to estimate the incremental cost-effectiveness ratio of
      LVADs compared with usual care. Despite the poor methodological quality of the 18
      studies included, LVADs appear beneficial improving survival, functional status,
      and quality of life. Adverse events are a serious concern. The economic
      evaluation showed that LVADs had a cost per quality adjusted life year of pound
      65,242 (95% confidence interval pound 34,194-364,564). Sensitivity analysis
      showed that post-heart transplant survival gains, pre-heart transplant patient
      utility, and one-off costs associated with implantation determine cost
      effectiveness. CONCLUSION: Although LVADs appear clinically effective as a BTT
      for people with ESHF, it is unlikely that they will be cost-effective unless
      costs decrease or the benefits of their use increase.

PMID- 16603578
TI  - Staphylococcal aortitis.

PMID- 16603579
TI  - Nationwide survey on acute heart failure in cardiology ward services in Italy.
AB  - AIMS: Chronic heart failure (HF) is recognized as an important public health
      problem but little attention has been focused on acute-stage HF. METHODS AND
      RESULTS: Nationwide, prospective, observational study setting 206 cardiology
      centres with intensive cardiac care units. During 3 months, 2807 patients
      diagnosed as having de novo acute HF (44%) or worsening chronic HF (56%) were
      enrolled. Acute pulmonary oedema was the presenting clinical feature in 49.6% of
      patients, cardiogenic shock in 7.7%, and worsened NYHA functional class in 42.7%
      of cases. Anaemia (Hb<12 g/dL) was present in 46% of patients, renal dysfunction
      (creatinine > or =1.5 mg%) in 47%, and hyponatraemia (< or =136 mEq/L) in 45%. An
      ejection fraction (EF)>40% was found in 34% of cases. Intravenous diuretics,
      nitrates, and inotropes were given to 95, 51, and 25% of patients, respectively.
      The median duration of hospital stay was 9 days. In-hospital mortality rate was
      7.3%. Older age, use of inotropic drugs, elevated troponin, hyponatraemia,
      anaemia, and elevated blood urea nitrogen were independent predictors of all
      cause death; prior revascularization procedures and elevated blood pressure were
      indicators of a better outcome. The rehospitalization rate within 6 months was
      38.1%, all-cause mortality from discharge to 6 months was 12.8%. CONCLUSION:
      Acute HF is an ominous condition, needing more research activity and resources.

PMID- 16603580
TI  - Benefits, challenges, and registerability of the polypill.
AB  - Guidelines for the management of cardiovascular disease (CVD) stress the
      importance of treating global risk, rather than individual risk, factors.
      Patients at high cardiovascular (CV) risk, for example, benefit from a
      combination of aspirin, antihypertensive agents, lipid-lowering drugs, and
      possibly folic acid. As the number of medications that a patient requires
      increases, adherence and compliance to therapy are likely to decrease. The use of
      affordable, multiple-target, fixed-combination 'polypills', which concomitantly
      reduce multiple risk factors without increasing the pill burden or the risk of
      adverse effects, has the potential to improve CV risk factor management, thereby
      reducing the incidence of CVD. This review discusses the benefits of the polypill
      and the challenges and requirements for its success and registerability.
      Discussions with regulatory bodies are required in order to obtain some 'balance'
      between an overcautious registration approach and the potentially large public
      health benefits that are likely to arise from the use of polypills.

PMID- 16603581
TI  - Preliminary evidence for cachexia in patients with well-established ankylosing
      spondylitis.
AB  - OBJECTIVES: Cachexia, defined as an accelerated loss of skeletal muscle in the
      context of a chronic inflammatory response, is common in rheumatoid arthritis but
      it has not been demonstrated in patients with ankylosing spondylitis (AS). The
      aim of this study was to determine muscle wasting and its functional consequences
      in a group of patients with well-established AS. METHODS: Nineteen male patients
      (mean age 53 yrs) with long-standing AS (mean disease duration 19 yrs) and
      radiological changes (84% had one or more syndesmophytes) were compared with 19
      age-matched healthy males with similar levels of habitual physical activity. Body
      composition was assessed by dual energy X-ray absorptiometry. Muscle strength was
      measured by isokinetic knee extension and hand grip dynamometry, and by 30 s arm
      curl and chair sit-to-stand tests. RESULTS: AS patients showed a statistically
      and clinically significant 12% reduction in arms and legs lean mass, a proxy
      measure of total body skeletal muscle mass, compared with healthy controls (P <
      0.05). This muscle loss was significantly associated with reduced upper and lower
      body strength (correlation coefficients ranging between 0.37 and 0.79, P < 0.05).
      CONCLUSION: These results provide preliminary evidence that cachexia is a
      functionally relevant systemic complication of AS, particularly in patients with
      long-standing disease and radiological changes. Progressive resistance training
      and other interventions aimed at stimulating skeletal muscle growth might be
      beneficial in this population, and further studies on the pathophysiology of
      cachexia in AS patients are needed.

PMID- 16603583
TI  - Safety of anti-TNF-alpha therapy in rheumatoid arthritis and spondylarthropathies
      with concurrent B or C chronic hepatitis.
AB  - OBJECTIVE: To assess the safety of anti-tumour necrosis factor (TNF)-alpha
      therapy in patients with rheumatoid arthritis (RA) or spondylarthropathies (SA)
      and concurrent chronic hepatitis B or C. METHODS: Records concerning 480
      outpatients attending the Rheumatology Department of the University Hospital of
      Nice (France) for RA or SA were retrospectively reviewed for the duration of
      disease, treatment, serological status and biological data. RESULTS: Six relevant
      cases were identified: two of RA with chronic hepatitis B; one of SA with chronic
      hepatitis B and three of RA with chronic hepatitis C. Five patients had received
      etanercept and one infliximab; two had been given adalimumab after an
      unsuccessful trial of etanercept. Patients with concurrent chronic hepatitis B
      were also given lamivudine. In none of the cases had changes in serum
      aminotransferases or viral load been reported. CONCLUSION: The use of anti-TNF
      alpha therapy (plus lamivudine in the presence of concurrent underlying hepatitis
      B viral infection) appeared to be safe in that it had no effect on serum
      aminotransferases and/or viral load. However, repeated monitoring is necessary
      throughout the treatment period.

PMID- 16603584
TI  - Appropriateness of colorectal cancer screening: appraisal of evidence by experts.
AB  - OBJECTIVE: . To evaluate how the level of evidence perceived by an international
      panel of experts was concordant with the level of evidence found in the
      literature, to compare experts perceived level of evidence to their
      appropriateness scores, and to compare appropriateness criteria for colonoscopy
      between experts and an evidence-based approach. DESIGN: Comparison of expert
      panel opinions and systematic literature review regarding the level of evidence
      and appropriateness of colonoscopy indications. PARTICIPANTS: European Panel on
      the Appropriateness of Gastrointestinal Endoscopy multidisciplinary experts from
      14 European countries. MAIN OUTCOME MEASURES: Concordance and weighted kappa
      coefficient between level of evidence as perceived by the experts' and that found
      in the literature, and between panel- and literature-based appropriateness
      categories. RESULTS: Experts overestimated the level of published evidence of 57
      indications. Concordance between the level of evidence perceived by the experts
      and the actual level of evidence found in the literature was 36% (weighted kappa
      0.18). Indications for colonoscopy were reported to be appropriate, uncertain,
      and inappropriate by the experts in 54, 19, and 27% of the cases, and by the
      literature in 37, 46, and 17% of the cases. A 46% agreement (weighted kappa 0.29)
      was found between literature-based and experts' appropriateness criteria.
      CONCLUSIONS: Experts often overestimated the level of evidence on which they
      based their decisions. However, rarely did the experts' judgement completely
      disagree with the literature, although concordance between panel- and literature
      based appropriateness was only fair. A more explicit discussion of existing
      evidence should be undertaken with the experts before they evaluate
      appropriateness criteria.

PMID- 16603585
TI  - Anti-CCR7 monoclonal antibodies as a novel tool for the treatment of chronic
      lymphocyte leukemia.
AB  - To date, chronic lymphocytic leukemia (CLL) remains incurable with current
      treatments, which include the monoclonal antibodies (mAbs) rituximab and
      alemtuzumab. The efficacy of rituximab is modest when used as single agent, and
      alemtuzumab induces severe immunosuppression. To develop more potent and specific
      therapies, we propose the CC chemokine receptor 7 (CCR7) as an attractive target
      molecule to treat CLL, as it not only fulfills the requirements of a high-surface
      expression and a good level of tissue specificity, but it also plays a crucial
      role in mediating the migration of the tumor cells to lymph nodes (LNs) and thus,
      in the development of clinical lymphadenopathy. In the current work, murine anti
      human CCR7 mAb mediated a potent, complement-dependent cytotoxicity (CDC) against
      CLL cells while sparing normal T lymphocytes from the same patients. The
      sensitivity to CDC was related to the antigenic density of CCR7. Moreover, these
      mAb blocked the in vitro migration of CLL cells in response to CC chemokine
      ligand 19 (CCL19), one of the physiological ligands of CCR7. Conversely, CLL
      cells were poorly lysed through antibody-dependent, cell-mediated cytotoxicity
      (ADCC), probably as a result of the murine origin and the isotype of the anti
      CCR7 mAb used. Molecular engineering techniques will allow us to obtain chimeric
      or humanized anti-CCR7 mAb to reach the best clinical response for this common
      and yet incurable leukemia.

PMID- 16603586
TI  - Bovine polymorphonuclear cells passively acquire membrane lipids and integral
      membrane proteins from apoptotic and necrotic cells.
AB  - Immune cells can acquire membrane fragments and integral membrane proteins from
      dead and dying cells or in the case of immature dendritic cells, from live cells.
      While investigating the possibility that bovine polymorphonuclear cells (PMNs)
      might present antigen, coculture assays confirmed that integral membrane proteins
      were transferred rapidly and efficiently to bovine PMNs from a variety of
      apoptotic and necrotic cells. Specifically, we observed that PMNs rapidly
      acquired proteins such as major histocompatibility complex (MHC) class II and CD3
      from a variety of syngeneic, allogeneic, and xenogeneic cell types. Such
      acquisition occurred within 40 min of PMN coculture with isolated peripheral
      blood mononuclear cells, and this acquisition occurred with equal efficiency at 4
      degrees C and 37 degrees C. The transfer of murine MHC class II to bovine PMNs
      precluded the possibility of endogenous protein expression. We also demonstrated
      the transfer of fluorescently labeled plasma membrane lipids and biotinylated
      integral membrane proteins. Collectively, these observations support the
      hypothesis that membrane protein transfer was mediated by the fusion of membrane
      fragments or microvesicles with the PMN plasma membrane and not by phagocytosis
      of cell fragments. These observations indicate that phenotypic studies of PMNs
      must consider circumstances whereby PMNs may passively acquire membrane lipids
      and a variety of integral membrane proteins from dead or dying cells.

PMID- 16603587
TI  - Macrophage nutriprive antimicrobial mechanisms.
AB  - In addition to oxidative and antibiotic mechanisms of antimicrobial activity,
      macrophages are able to deprive intracellular pathogens of required nutrients.
      Thus, microbial killing may not rely only in the toxic environment the microbe
      reaches but also may result from the scarcity of nutrients in the cellular
      compartment it occupies. Here, we analyze evidence for such nutriprive (from the
      latin privare, to deprive of nutrients), antimicrobial mechanisms. Although the
      direct analysis of nutrient availability is most often not feasible, indirect
      evidence of lack of nutrients in the microbial organelles has been inferred from
      the study of mutants, the analysis of gene expression, and the consequences of
      changing the intracellular location of the pathogen. We propose that according to
      the microbe and its survival strategy, different mechanisms to impede access to
      nutrients may be constitutively present or may be induced by cytokines and other
      pathways. Thus, membrane transporters may remove nutrients from vacuolar
      compartments, and enzymes may degrade some growth factors. A series of diverse
      compounds may sequester other molecules required for microbial growth, as
      exemplified by the action of iron chelators. Modulation of vesicular trafficking
      may prevent the fusion of certain vesicles containing nutrients with those
      containing the pathogen, counteracting the evasion strategies of the pathogen.
      The understanding of these mechanisms will certainly help in designing new
      therapeutic and prophylactic approaches to preventing infectious diseases.

PMID- 16603588
TI  - Neutrophil role in pulmonary paracoccidioidomycosis depends on the resistance
      pattern of hosts.
AB  - The immunoprotective and immunomodulatory role of neutrophils during pulmonary
      infection of resistant (A/J) and susceptible (B10.A) mice to Paracoccidioides
      brasiliensis was investigated. First, comparative studies about early cellular
      influx to the lungs demonstrated higher numbers of neutrophils in susceptible
      rather than in resistant mice. Neutrophil depletion resulted in decreased
      survival times of susceptible but not resistant mice. In both mouse strains,
      depletion led to increased fungal burdens at Week 1 of infection; however, only
      susceptible mice remained with increased pulmonary fungal loads and presented a
      dramatic fungal dissemination to liver and spleen. At Week 1 of infection,
      treated and untreated B10.A and A/J mice were negative for delayed-type
      hypersensitivity (DTH) reactions, which remained negative for the susceptible
      strain. In contrast, from the second week onward, control and neutrophil
      depleted, resistant mice became positive for DTH reactions. In B10.A mice,
      neutrophil depletion resulted in increased levels of interleukin (IL)-12 and IL-4
      in the lungs, high levels of hepatic cytokines, and increased synthesis of T
      helper cell type 1 (Th1)- and Th2-regulated antibodies [immunoglobulin G1 (IgG1),
      IgA, and IgG3]. In neutrophil-depleted A/J mice, high levels of pulmonary IL-12
      and granulocyte macrophage-colony stimulating factor were concomitant to
      diminished levels of hepatic cytokines and increased amounts of Th1-regulated
      isotypes (IgG2a, IgG2b, and IgG3). Differently from primary infection, neutrophil
      depletion did not alter immunoprotection in secondary paracoccidioidomycosis. As
      a whole, our data showed that the genetic patterns of hosts exert an important
      influence on the immunoprotective and immunoregulatory functions of neutrophils,
      which appear to be essential in situations devoid of cell-mediated immunity.

PMID- 16603589
TI  - Molecular basis of age-associated cytokine dysregulation in LPS-stimulated
      macrophages.
AB  - Aged humans and rodents are susceptible to infection with Streptococcus
      pneumoniae bacteria as a result of an inability to make antibodies to capsular
      polysaccharides. This is partly a result of decreased production of
      proinflammatory cytokines and increased production of interleukin (IL)-10 by
      macrophages (Mphi) from aged mice. To understand the molecular basis of cytokine
      dysregulation in aged mouse Mphi, a microarray analysis was performed on RNA from
      resting and lipopolysaccharide (LPS)-stimulated Mphi from aged and control mice
      using the Affymetrix Mouse Genome 430 2.0 gene chip. Two-way ANOVA analysis
      demonstrated that at an overall P < 0.01 level, 853 genes were regulated by LPS
      (169 in only the young, 184 in only the aged, and 500 in both). Expression
      analysis of systematic explorer revealed that immune response (proinflammatory
      chemokines, cytokines, and their receptors) and signal transduction genes were
      specifically reduced in aged mouse Mphi. Accordingly, expression of Il1 and Il6
      was reduced, and Il10 was increased, confirming our previous results. There was
      also decreased expression of interferon-gamma. Genes in the Toll-like receptor
      signaling pathway leading to nuclear factor-kappaB activation were also down
      regulated but IL-1 receptor-associated kinase 3, a negative regulator of this
      pathway, was increased in aged mice. An increase in expression of the gene for
      p38 mitogen-activated protein kinase (MAPK) was observed with a corresponding
      increase in protein expression and enzyme activity confirmed by Western blotting.
      Low doses of a p38 MAPK inhibitor (SB203580) enhanced proinflammatory cytokine
      production by Mphi and reduced IL-10 levels, indicating that increased p38 MAPK
      activity has a role in cytokine dysregulation in the aged mouse Mphi.

PMID- 16603590
TI  - Mechanotransduction of stretch-induced prostanoid release by fetal lung
      epithelial cells.
AB  - Mechanical ventilation is the primary supportive treatment for infants and adults
      suffering from severe respiratory failure. Adverse mechanical ventilation
      (overdistension of the lung) triggers a proinflammatory response. Along with
      cytokines, inflammatory mediators such as bioactive lipids are involved in the
      regulation of the inflammatory response. The arachidonic acid pathway is a key
      source of bioactive lipid mediators, including prostanoids. Although ventilation
      has been shown to influence the production of prostanoids in the lung, the
      mechanotransduction pathways are unknown. Herein, we established that cyclic
      stretch of fetal lung epithelial cells, but not fibroblasts, can evoke an
      extremely sensitive, rapid alteration in eicosanoid metabolism through a
      cyclooxygenase (COX)-2 dependent mechanism. Cyclic stretch significantly
      increased PGI(2), PGF(2alpha), PGD(2), PGE(2), and thromboxane B(2) levels in the
      media of epithelial cells, but did not alter leukotriene B(4) or 12
      hydroxyeicosatetraenoic acid levels. Inhibition of COX-2, but not COX-1,
      attenuated the cyclic stretch-induced PG increase in the media, suggesting that
      cyclic stretch primarily affected PG synthesis. Substrate (free arachidonic acid)
      availability for PG generation was increased because of a cyclic stretch-induced
      activation of cytosolic phospholipase A(2) (cPLA(2)) via an influx of
      extracellular calcium and phosphorylation by mitogen-activated protein kinase,
      p44/42MAPK. The data are compatible with cPLA(2) and COX-2 being intimately
      involved in regulating the injury response to adverse mechanical ventilation.

PMID- 16603591
TI  - Peristalsis of airway smooth muscle is developmentally regulated and uncoupled
      from hypoplastic lung growth.
AB  - Prenatal airway smooth muscle (ASM) peristalsis appears coupled to lung growth.
      Moreover, ASM progenitors produce fibroblast growth factor-10 (FGF-10) for lung
      morphogenesis. Congenital diaphragmatic hernia (CDH) is associated with lung
      hypoplasia, FGF-10 deficiency, and postnatal ASM dysfunction. We hypothesized ASM
      dysfunction emerges in tandem with, and may contribute toward, the primordial
      lung hypoplasia that precedes experimental CDH. Spatial origin and frequency of
      ASM peristaltic waves were measured in normal and hypoplastic rat lungs cultured
      from day 13.5 of gestation (lung hypoplasia was generated by nitrofen dosing of
      pregnant dams). Longitudinal lung growth was assayed by bud counts and tracing
      photomicrographs of cultures. Coupling of lung growth and peristalsis was tested
      by stimulation studies using serum, FGF-10, or nicotine and inhibition studies
      with nifedipine or U0126 (MEK1/2 inhibitor). In normal lung, ASM peristalsis is
      developmentally regulated: proximal ASM becomes quiescent (while retaining
      capacity for cholinergic-stimulated peristalsis). However, in hypoplastic lung,
      spontaneous proximal ASM activity persists. FGF-10 corrects this aberrant ASM
      activity in tandem with improved growth. Stimulation and inhibition studies
      showed that, unlike normal lung, changes in growth or peristalsis are not
      consistently accompanied by parallel modulation of the other. ASM peristalsis
      undergoes FGF-10-regulated spatiotemporal development coupled to lung growth:
      this process is disrupted early in lung hypoplasia. ASM dysfunction emerges in
      tandem with and may therefore contribute toward lung hypoplasia in CDH.

PMID- 16603592
TI  - Protective effects of S-nitrosoalbumin on lung injury induced by hypoxia
      reoxygenation in mouse model of sickle cell disease.
AB  - Nitric oxide (NO) is a potential new therapeutic agent for sickle cell disease
      (SCD). We investigated the effects of NO donor on hypoxia-induced acute lung
      injury that occurs when transgenic sickle cell SAD mice are exposed to chronic
      hypoxia, a model for lung vasoocclusive sickle cell events. In wild-type and SAD
      mice, intraperitoneal injection of S-nitrosoalbumin (NO-Alb) produced no
      significant hematologic changes under room air conditions, whereas it induced
      mild temporary hypotension and inhibition of platelet aggregation. NO-Alb
      administration (300 mg/kg ip twice a day, equivalent to 7.5 microM NO) in wild
      type and SAD mice exposed to 46 h of hypoxia (8% oxygen) followed by 2 h of
      normoxia resulted in 1) reduction of the hypoxia-induced increase in blood
      neutrophil count, 2) prevention of hypoxia-induced increased IL-6 and IL-1beta
      levels in bronchoalveolar lavage, 3) reduction of the lung injury induced by
      hypoxia-reoxygenation, 4) prevention of thrombus formation, and 5) prevention of
      hypoxia-induced increase of lung matrix metalloproteinase-9 gene expression.
      These effects provide new insights into the possible use of NO-Alb in the
      treatment of acute lung injury in SCD.

PMID- 16603594
TI  - Endocytosis pathways in endothelium: how many?

PMID- 16603593
TI  - Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis
      of inflammatory lung diseases.
AB  - Inducible cyclooxygenase (COX-2) and its metabolites have diverse and potent
      biological actions that are important for both physiological and disease states
      of lung. The wide variety of prostaglandin (PG) products are influenced by the
      level of cellular activation, the exact nature of the stimulus, and the specific
      cell type involved in their production. In turn, the anti- and proinflammatory
      response of PG is mediated by a blend of specific surface and intracellular
      receptors that mediate diverse cellular events. The complexity of this system is
      being at least partially resolved by the generation of specific molecular
      biological research tools that include cloning and characterization of the
      enzymes distal to COX-2 and the corresponding receptors to the final cellular
      products of arachidonic metabolism. The most informative of these approaches have
      employed genetically modified animals and specific receptor antagonists to
      determine the exact role of specific COX-2-derived metabolites on specific cell
      types of the lung in the context of inflammatory models. These data have
      suggested a number of cell-specific, pathway-specific, and receptor-specific
      approaches that could lead to effective therapeutic interventions for most
      inflammatory lung diseases.

PMID- 16603595
TI  - S-nitrosothiols regulate cell-surface pH buffering by airway epithelial cells
      during the human immune response to rhinovirus.
AB  - Human rhinovirus infection is a common trigger for asthma exacerbations. Asthma
      exacerbations and rhinovirus infections are both associated with markedly
      decreased pH and ammonium levels in exhaled breath condensates. This observation
      is thought to be related, in part, to decreased activity of airway epithelial
      glutaminase. We studied whether direct rhinovirus infection and/or the host
      immune response to the infection decreased airway epithelial cell surface pH in
      vitro. Interferon-gamma and tumor necrosis factor-alpha, but not direct
      rhinovirus infection, decreased pH, an effect partly associated with decreased
      ammonium concentrations. This effect was 1) prevented by nitric oxide synthase
      inhibition; 2) independent of cyclic GMP; 3) associated with an increase in
      endogenous airway epithelial cell S-nitrosothiol concentration; 4) mimicked by
      the exogenous S-nitrosothiol, S-nitroso-N-acetyl cysteine; and 5) independent of
      glutaminase expression and activity. We then confirmed that decreased epithelial
      pH inhibits human rhinovirus replication in airway epithelial cells. These data
      suggest that a nitric oxide synthase-dependent host response to viral infection
      mediated by S-nitrosothiols, rather than direct infection itself, plays a role in
      decreased airway surface pH during human rhinovirus infection. This host immune
      response may serve to protect the lower airways from direct infection in the
      normal host. In patients with asthma, however, this fall in pH could be
      associated with the increased mucus production, augmented inflammatory cell
      degranulation, bronchoconstriction, and cough characteristic of an asthma
      exacerbation.

PMID- 16603596
TI  - Antigen sensitization modulates alveolar macrophage functions in an asthma model.
AB  - We have previously demonstrated that adoptive transfer of alveolar macrophages
      from allergy-resistant rats to alveolar macrophage-depleted allergic rats
      prevents airway hyperresponsiveness development, suggesting an important role for
      alveolar macrophages in asthma pathogenesis. Given that ovalbumin sensitization
      can modulate alveolar macrophage cytokine production, we investigated the role of
      sensitized and unsensitized alveolar macrophages in an asthma model. Alveolar
      macrophages from unsensitized or sensitized Brown Norway rats were transferred to
      alveolar macrophage-depleted sensitized rats 24 h before allergen challenge.
      Airway responsiveness to methacholine and airway inflammation were measured the
      following day. Methacholine concentration needed to increase lung resistance by
      200% was significantly higher in alveolar macrophage-depleted sensitized rats
      that received unsensitized alveolar macrophages compared with alveolar macrophage
      depleted sensitized rats that received sensitized alveolar macrophages. Tumor
      necrosis factor levels in bronchoalveolar lavage fluid of sensitized rats that
      received unsensitized alveolar macrophages were significantly lower compared with
      rats that received sensitized alveolar macrophages. Interestingly, alveolar
      macrophages of unsensitized animals showed higher phagocytosis activity compared
      with alveolar macrophages of sensitized rats, suggesting that sensitization
      modulates alveolar macrophage phagocytosis function. Our data suggest an
      important role of allergen sensitization on alveolar macrophage function in
      asthma pathogenesis.

PMID- 16603597
TI  - Modifications of proteins by 4-hydroxy-2-nonenal in the ventilatory muscles of
      rats.
AB  - Although 4-hydroxy-2-nonenal (HNE, a product of lipid peroxidation) is a major
      cause of oxidative damage inside skeletal muscles, the exact proteins modified by
      HNE are unknown. We used two-dimensional electrophoresis, immunoblotting, and
      mass spectrometry to identify selective proteins targeted by HNE inside the
      diaphragm of rats under two conditions: severe sepsis [induced by E. coli
      lipopolysaccharides (LPS)] and during strenuous muscle contractions elicited by
      severe inspiratory resistive loading (IRL). Diaphragm HNE-protein adduct
      formation (detected with a polyclonal antibody) increased significantly after 1
      and 3 h of LPS injection with a return to baseline values thereafter. Similarly,
      HNE-protein adduct formation inside the diaphragm rose significantly after 6 but
      not 3 h of IRL. Mass spectrometry analysis of HNE-modified proteins revealed
      enolase 3b, aldolase and triosephosphate isomerase 1, creatine kinase, carbonic
      anyhdrase III, aconitase 2, dihydrolipoamide dehydrogenase, and electron transfer
      flavoprotein-beta. Measurements of in vitro enolase activity in the presence of
      pure HNE revealed that HNE significantly attenuated enolase activity in a dose
      dependent fashion, suggesting that HNE-derived modifications have inhibitory
      effects on enzyme activity. We conclude that lipid peroxidation products may
      inhibit muscle contractile performance through selective targeting of enzymes
      involved in glycolysis, energy production as well as CO(2) hydration.

PMID- 16603598
TI  - Prospective trial on topotecan salvage therapy in primary CNS lymphoma.
AB  - BACKGROUND: Standard salvage therapy has not been established for recurrent
      primary central nervous system lymphoma (PCNSL). We report the final results of a
      prospective study on topotecan chemotherapy in relapsed or refractory PCNSL.
      PATIENTS AND METHODS: The study included 27 patients with a median age of 51
      years and an ECOG performance status of 2. Fourteen patients were refractory to
      the last therapy, and 13 relapsed after a median period of 6.0 months.
      Pretreatment with up to four regimens included chemotherapy in 26 patients and
      whole brain irradiation in 14. A 30-min daily topotecan infusion of 1.5 mg/m(2)
      for 5 days was repeated every 3 weeks. RESULTS: The response rate was 33% with
      five complete (CR) and four partial remissions (PR). The median follow-up was
      37.7 months. All complete responders had sustained remissions lasting for 9 to 28
      months. The median event-free survival (EFS) was 2.0 months (9.1 months in
      responders), the overall survival (OAS) was 8.4 months. CTC grade 3-4 leukopenia
      occurred in 26% and thrombocytopenia in 11% of the patients. Eight of 12 patients
      alive without cerebral lymphoma > or = six months after topotecan exhibited
      deficits attributable to late neurotoxicity. CONCLUSION: Topotecan as monotherapy
      is active in relapsed and refractory PCNSL with tolerable toxicity.

PMID- 16603599
TI  - A phase III trial of docetaxel/carboplatin versus mitomycin
      C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in
      patients with advanced non-small-cell lung cancer: a randomised multicentre trial
      of the British Thoracic Oncology Group (BTOG1).
AB  - BACKGROUND: Phase III studies suggest that non-small-cell lung cancer (NSCLC)
      patients treated with cisplatin-docetaxel may have higher response rates and
      better survival compared with other platinum-based regimens. We report the final
      results of a randomised phase III study of docetaxel and carboplatin versus MIC
      or MVP in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with
      biopsy proven stage III-IV NSCLC not suitable for curative surgery or
      radiotherapy were randomised to receive four cycles of either DCb (docetaxel 75
      mg/m(2), carboplatin AUC 6), or MIC/MVP (mitomycin 6 mg/m(2), ifosfamide 3 g/m(2)
      and cisplatin 50 mg/m(2) or mitomycin 6 mg/m(2), vinblastine 6 mg/m(2) and
      cisplatin 50 mg/m(2), respectively), 3 weekly. The primary end point was
      survival, secondary end points included response rates, toxicity and quality of
      life. RESULTS: The median follow-up was 17.4 months. Overall response rate was
      32% for both arms (partial response = 31%, complete response = 1%); 32% of
      MIC/MVP and 26% of DCb patients had stable disease. One-year survival was 39% and
      35% for DCb and MIC/MVP, respectively. Two-year survival was 13% with both arms.
      Grade 3/4 neutropenia (74% versus 43%, P < 0.005), infection (18% versus 9%, P =
      0.01) and mucositis (5% versus 1%, P = 0.02) were more common with DCb than
      MIC/MVP. The MIC/MVP arm had significant worsening in overall EORTC score and
      global health status whereas the DCb arm showed no significant change.
      CONCLUSIONS: The combination of DCb had similar efficacy to MIC/MVP but quality
      of life was better maintained.

PMID- 16603600
TI  - Phase II study of combination therapy with S-1 and irinotecan in patients with
      advanced colorectal cancer.
AB  - BACKGROUND: A combination of irinotecan with continuous intravenous infusions of
      5-fluorouracil (5-FU) and leucovorin (LV) is often used to treat advanced
      colorectal cancer. However, recent concerns about safety and convenience have
      prompted the development of new oral fluoropyrimidine derivatives and improved
      regimens. This phase II study evaluated the efficacy and safety of the oral
      fluoropyrimidine S-1 plus irinotecan in patients with previously untreated
      advanced or recurrent colorectal cancer. PATIENTS AND METHODS: Forty eligible
      patients with histologically confirmed colorectal adenocarcinoma received this
      treatment. S-1 was administered orally on days 1 to 14 of a 21-day cycle.
      Patients were assigned on the basis of body surface area (BSA) to receive one of
      the following oral doses twice daily: 40 mg (BSA < 1.25 m(2)), 50 mg (BSA > or =
      1.25 to < 1.50 m(2)), or 60 mg (BSA > or = 1.50 m(2)). Irinotecan (150 mg/m(2))
      was administered by intravenous infusion on day 1. RESULTS: A total of 327
      courses of treatment were administered to 40 patients. Five patients had complete
      responses, and 20 had partial responses. The overall response rate was 62.5% (95%
      confidential interval, 47.5%-77.5%). Median progression-free survival was 8.0
      months (95% confidential interval, 5.2-11.4 months). The rates of grade 3 or 4
      toxicity were as follows: neutropenia, 15%; anemia, 7.5%; anorexia, 12.5%; and
      diarrhea, 7.5%. CONCLUSIONS: Combined treatment with S-1 and irinotecan is an
      effective, well tolerated, and convenient regimen in patients with advanced
      colorectal cancer. Our findings suggest that combined treatment with S-1 and
      irinotecan is a promising regimen, offering benefits in terms of safety and
      survival as compared with conventional regimens in patients with advanced
      colorectal cancer.

PMID- 16603601
TI  - Identifying breast cancer patients at risk for Central Nervous System (CNS)
      metastases in trials of the International Breast Cancer Study Group (IBCSG).
AB  - BACKGROUND: We sought to determine whether a high-risk group could be defined
      among patients with operable breast cancer in whom a search of occult central
      nervous system (CNS) metastases was justified. PATIENTS AND METHODS: We evaluated
      data from 9524 women with early breast cancer (42% node-negative) who were
      randomized in International Breast Cancer Study Group clinical trials between
      1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We
      identified patients whose site of first event was CNS and those who had a CNS
      event at any time. RESULTS: Median follow-up was 13 years. The 10-year incidence
      (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of
      CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3
      N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3
      (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor
      negative and node-positive (2.6%). The risk of subsequent CNS recurrence was
      elevated in patients experiencing lung metastases (10-yr = 16.4%). CONCLUSION:
      Based on this large cohort we were able to define risk factors for CNS
      metastases, but could not define a group at sufficient risk to justify routine
      screening for occult CNS metastases.

PMID- 16603602
TI  - Apoptosis in liver during malaria: role of oxidative stress and implication of
      mitochondrial pathway.
AB  - Hepatic dysfunction is a common clinical complication in malaria, although its
      pathogenesis remains largely unknown. Using a variety of in vivo and ex vivo
      approaches, we have shown for the first time that malarial infection induces
      hepatic apoptosis through augmentation of oxidative stress. Apoptosis in
      hepatocyte has been confirmed by terminal deoxynucleotidyl transferase (TdT)
      mediated dUTP-biotin-nick-end labeling assay (TUNEL) and caspase-3 activation.
      Gene expression analysis using RT-PCR indicates the significant down-regulation
      of Bcl-2 and up-regulation of Bax expression in liver of malaria infected mice
      suggesting the involvement of mitochondrial pathway of apoptosis. The levels of
      Fas expression and caspase-8 activity in infected liver were same as that of
      uninfected control mice indicating death receptor (Fas) pathway did not
      contribute to liver apoptosis during malarial infection. Moreover, evidence has
      been presented by confocal microscopy to show the translocation of Bax from
      cytosol to mitochondria in apoptotic hepatocyte, resulting in opening of
      permeability transition pores, which in turn decreases mitochondrial membrane
      potential and induces cytochrome c release into cytosol. Malarial infection
      induces the generation of hydroxyl radical (*OH) in liver, which may be
      responsible for the induction of oxidative stress and apoptosis as administration
      of *OH specific antioxidant as well as spin trap, alpha-phenyl-tert-butyl-nitrone
      in malaria-infected mice significantly inhibits the development of oxidative
      stress as well as induction of apoptosis. Thus, results suggest the implication
      of oxidative stress induced-mitochondrial pathway of apoptosis in the
      pathophysiology of hepatic dysfunction in malaria.

PMID- 16603604
TI  - Cyclin D1 degradation enhances endothelial cell survival upon oxidative stress.
AB  - The understanding of endothelial cell responses to oxidative stress may provide
      insights into aging mechanisms and into the pathogenesis of numerous
      cardiovascular diseases. In this study, we examined the regulation and the
      functional role of cyclin D1, a crucial player in cell proliferation and
      survival. On H2O2 treatment, endothelial cells showed a rapid down-modulation of
      cyclin D1. Other D-cyclins were similarly regulated, and this decrease was also
      observed after exposure to other oxidative stress-inducing stimuli, namely 1,3
      bis (2 chloroethyl)-1 nitrosourea treatment and ischemia. H2O2 treatment induced
      cyclin D1 ubiquitination followed by proteasome degradation. Phospholipase C
      inhibition prevented cyclin D1 degradation, and its activation triggered cyclin
      D1 down-modulation in the absence of oxidative stress. Activated phospholipase C
      generates inositol-1,4,5-trisphosphate (IP3) and Ca2+ release from internal
      stores. We found that both IP3-receptor inhibition and intracellular Ca2+
      chelation prevented cyclin D1 degradation induced by oxidative stress.
      Furthermore, Ca2+ increase was transduced by Ca2+/calmodulin-dependent protein
      kinase (CaMK). In fact, H2O2 stimulated CaMK activity, CaMK inhibitors prevented
      H2O2-induced cyclin D1 down-modulation, and CaMK overexpression induced cyclin D1
      degradation. Finally, overriding of cyclin D1 down-modulation via its forced
      overexpression or via CaMK inhibition increased cell sensitivity to H2O2-induced
      apoptotic cell death. Thus, cyclin D1 degradation enhances endothelial cell
      survival on oxidative stress.

PMID- 16603603
TI  - Receptor-mediated oral delivery of a bioencapsulated green fluorescent protein
      expressed in transgenic chloroplasts into the mouse circulatory system.
AB  - Oral delivery of biopharmaceutical proteins expressed in plant cells should
      reduce their cost of production, purification, processing, cold storage,
      transportation, and delivery. However, poor intestinal absorption of intact
      proteins is a major challenge. To overcome this limitation, we investigate here
      the concept of receptor-mediated oral delivery of chloroplast-expressed foreign
      proteins. Therefore, the transmucosal carrier cholera toxin B-subunit and green
      fluorescent protein (CTB-GFP), separated by a furin cleavage site, was expressed
      via the tobacco chloroplast genome. Polymerase chain reaction (PCR) and Southern
      blot analyses confirmed site-specific transgene integration and homoplasmy.
      Immunoblot analysis and ELISA confirmed expression of monomeric and pentameric
      forms of CTB-GFP, up to 21.3% of total soluble proteins. An in vitro furin
      cleavage assay confirmed integrity of the engineered furin cleavage site, and a
      GM1 binding assay confirmed the functionality of CTB-GFP pentamers. Following
      oral administration of CTB-GFP expressing leaf material to mice, GFP was observed
      in the mice intestinal mucosa, liver, and spleen in fluorescence and
      immunohistochemical studies, while CTB remained in the intestinal cell. This
      report of receptor-mediated oral delivery of a foreign protein into the
      circulatory system opens the door for low-cost production and delivery of human
      therapeutic proteins.

PMID- 16603605
TI  - Charged particle equilibrium effects on the electron absorbed fraction in the
      extrathoracic airways.
AB  - Estimates of the dose to the extrathoracic airway (nasal vestibule) from inhaled
      beta-emitting radionuclides, obtained using the respiratory tract model presented
      in Publication 66 of the International Commission on Radiological Protection,
      frequently predict that the basal cells in this region are the most highly
      irradiated tissues of the body. The dose to the basal cells is averaged over a
      layer of tissue 10 microm thick located at a depth of 40 microm into the airway
      assuming that charged particle equilibrium exists. Since the target (basal cell
      layer) is very small and thin (10 cm(2) area and 10 microm thickness), charged
      particle equilibrium does not exist. In this work the effect on the absorbed
      fraction of the lack of charged particle equilibrium is investigated.

PMID- 16603606
TI  - Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a
      randomized trial.
AB  - RATIONALE: In patients with community-acquired pneumonia, guidelines recommend
      antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial
      infections, and its dynamics have prognostic implications. OBJECTIVE: To assess
      procalcitonin guidance for the initiation and duration of antibiotic therapy in
      community-acquired pneumonia. METHODS: In a randomized intervention trial, 302
      consecutive patients with suspected community-acquired pneumonia were included.
      Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk. The control
      group (n = 151) received antibiotics according to usual practice. In the
      procalcitonin group (n = 151), antibiotic treatment was based on serum
      procalcitonin concentrations as follows: strongly discouraged, less than 0.1
      microg/L; discouraged, less than 0.25 microg/L; encouraged, greater than 0.25
      microg/L; strongly encouraged, greater than 0.5 microg/L. The primary endpoint
      was antibiotic use; secondary endpoints were measures of clinical, laboratory,
      and radiographic outcome. RESULTS: At baseline, both groups were similar
      regarding clinical, laboratory, and microbiology characteristics, and Pneumonia
      Severity Index. Procalcitonin guidance reduced total antibiotic exposure
      (relative risk, 0.52; 95% confidence interval, 0.48-0.55; p < 0.001), antibiotic
      prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment
      duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according
      to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of
      antibiotic discontinuation was higher in the procalcitonin group than in the
      control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in
      both groups, with an overall success rate of 83%. CONCLUSIONS: Procalcitonin
      guidance substantially reduces antibiotic use in community-acquired pneumonia.
      These findings may have important clinical and public health implications.

PMID- 16603607
TI  - Bombesin inhibits alveolarization and promotes pulmonary fibrosis in newborn
      mice.
AB  - RATIONALE: Bombesin-like peptides promote fetal lung development. Normally,
      levels of mammalian bombesin (gastrin-releasing peptide [GRP]) drop postnatally,
      but these levels are elevated in newborns that develop bronchopulmonary dysplasia
      (BPD), a chronic lung disease characterized by arrested alveolarization. In
      premature baboons with BPD, antibombesin antibodies reduce lung injury and
      promote alveolarization. OBJECTIVES: The present study tests whether exogenous
      bombesin or GRP given perinatally alters alveolar development in newborn mice.
      METHODS: Mice were given peptides intraperitoneally twice daily on Postnatal Days
      1-3. On Day 14 lungs were inflation-fixed for histopathologic analyses of
      alveolarization. MEASUREMENTS AND MAIN RESULTS: Bombesin had multiple effects on
      Day 14 lung, when alveolarization was about half complete. First, bombesin
      induced alveolar myofibroblast proliferation and increased alveolar wall
      thickness compared with saline-treated control animals. Second, bombesin
      diminished alveolarization in C57BL/6 (but not Swiss-Webster) mice. We used
      receptor-null mice to explore which receptors might mediate these effects.
      Compared with wild-type littermates, bombesin-treated GRP receptor (GRPR)-null
      mice had increased interstitial fibrosis but reduced defects in alveolarization.
      Neuromedin B (NMB) receptor-null and bombesin receptor subtype 3-null mice had
      the same responses as their wild-type littermates. GRP had the same effects as
      bombesin, whereas neither NMB nor a synthetic bombesin receptor type 3 ligand had
      any effect. All effects of GRP were abrogated in GRPR-null mice. CONCLUSIONS:
      Bombesin/GRP can induce features of BPD, including interstitial fibrosis and
      diminished alveolarization. GRPR appears to mediate all effects of GRP, but only
      part of the bombesin effect on alveolarization, suggesting that novel receptors
      may mediate some effects of bombesin in newborn lung.

PMID- 16603608
TI  - Modified Th2 responses at high-dose exposures to allergen: using an occupational
      model.
AB  - RATIONALE: The relationships between allergen exposures and allergy and asthma
      are complex. High exposure levels to cat allergen are associated with IgG- and
      IgG(4)-specific antibody responses without sensitization or risk of asthma, a
      process described as a "modified Th2 response." Attenuation of risk of allergy
      and asthma at high exposure levels has been reported in longitudinal studies of
      both childhood and occupational asthma. OBJECTIVES: To investigate, using an
      occupational model, the relationships among estimated exposure to aeroallergens,
      the production of specific IgE, IgG and IgG(4) antibodies, and the prevalence of
      associated symptoms. METHODS: Cross-sectional survey of employees exposed to rats
      at work on six pharmaceutical sites across the United Kingdom. A total of 689
      (89%) provided a blood sample and completed a questionnaire. MEASUREMENTS AND
      MAIN RESULTS: At highest exposure to rats, there was an attenuation of the
      exposure response for sensitization and symptoms. In contrast, the frequency of
      individuals producing high quantities of specific IgG and IgG(4) increased with
      exposure intensity. Ratios of IgG(4)/IgE were highest in those handling the
      greatest number of rats. Risk of developing work-related chest symptoms was lower
      for those who produced both specific IgE and IgG(4) compared to those with
      specific IgE only. CONCLUSIONS: High exposure to rats is associated with lower
      rates of specific IgE and symptoms but an increased frequency of high specific
      IgG and IgG(4) production. Specific IgG(4) produced together with specific IgE
      may reduce the risk of developing work-related chest symptoms compared with when
      specific IgE is produced alone.

PMID- 16603609
TI  - Oral decontamination with chlorhexidine reduces the incidence of ventilator
      associated pneumonia.
AB  - RATIONALE: Ventilator-associated pneumonia (VAP) is the most frequently occurring
      nosocomial infection associated with increased morbidity and mortality. Although
      oral decontamination with antibiotics reduces incidences of VAP, it is not
      recommended because of potential selection of antibiotic-resistant pathogens. We
      hypothesized that oral decontamination with either chlorhexidine (CHX, 2%) or
      CHX/colistin (CHX/COL, 2%/2%) would reduce and postpone development of VAP, and
      oral and endotracheal colonization. OBJECTIVES: To determine the effect of oral
      decontamination with CHX or CHX/COL on VAP incidence and time to development of
      VAP. METHODS: Consecutive patients needing mechanical ventilation for 48 h or
      more were enrolled in a randomized, double-blind, placebo-controlled trial with
      three arms: CHX, CHX/COL, and placebo (PLAC). Trial medication was applied every
      6 h into the buccal cavity. Oropharyngeal swabs were obtained daily and
      quantitatively analyzed for gram-positive and gram-negative microorganisms.
      Endotracheal colonization was monitored twice weekly. RESULTS: Of 385 patients
      included, 130 received PLAC, 127 CHX and 128 CHX/COL. Baseline characteristics
      were comparable. The daily risk of VAP was reduced in both treatment groups
      compared with PLAC: 65% (hazard ratio [HR]=0.352; 95% confidence interval [CI],
      0.160, 0. 791; p=0.012) for CHX and 55% (HR=0.454; 95% CI, 0.224, 0. 925;
      p=0.030) for CHX/COL. CHX/COL provided significant reduction in oropharyngeal
      colonization with both gram-negative and gram-positive microorganisms, whereas
      CHX mostly affected gram-positive microorganisms. Endotracheal colonization was
      reduced for CHX/COL patients and to a lesser extent for CHX patients. No
      differences in duration of mechanical ventilation, intensive care unit stay, or
      intensive care unit survival could be demonstrated. CONCLUSIONS: Topical oral
      decontamination with CHX or CHX/COL reduces the incidence of VAP.

PMID- 16603611
TI  - Laboratory diagnostic systems for Ebola and Marburg hemorrhagic fevers developed
      with recombinant proteins.

PMID- 16603610
TI  - Immune containment and consequences of measles virus infection in healthy and
      immunocompromised individuals.

PMID- 16603612
TI  - Platelet-activating factor-acetylhydrolase can monodeacylate and inactivate
      lipoteichoic acid.
AB  - Bacterial lipoteichoic acid (LTA) shares a structural motif with platelet
      activating factor (PAF). Both molecules are strong inflammatory agents and have a
      glycerol backbone with two lipid chains at the sn-1 and sn-2 positions. PAF is
      normally inactivated by PAF-acetylhydrolase (PAF-AH), a phospholipase A2 (PLA2),
      which removes a short acyl group at the sn-2 position. To investigate whether PAF
      AH can similarly degrade LTA, we studied the effects of porcine PLA2, bee venom
      PLA2, and recombinant human PAF-AH on pneumococcal LTA (PnLTA) and staphylococcal
      LTA (StLTA). After incubation with a porcine or bee venom PLA2, a large fraction
      of PnLTA lost 264 Da, which corresponds to the mass of the oleic acid group at
      the sn-2 position. After incubation with recombinant human PAF-AH, PnLTA lost 264
      Da; the reduction did not occur when PAF-AH was exposed to Pefabloc SC, an
      irreversible inhibitor of the PAF-AH active site. Following PAF-AH treatment,
      PnLTA and StLTA were not able to stimulate mouse RAW 264.7 cells to produce tumor
      necrosis factor alpha but could stimulate CHO cells expressing human TLR2. This
      stimulation pattern has been observed with monoacyl PnLTA prepared by mild alkali
      hydrolysis (22). Taking these data together, we conclude that PAF-AH can remove
      one acyl chain at the sn-2 position of LTA and produce a monoacyl-LTA that is
      inactive against mouse cells.

PMID- 16603613
TI  - Evaluation of multiplex flow cytometric opsonophagocytic assays for determination
      of functional anticapsular antibodies to Streptococcus pneumoniae.
AB  - The determination of functional antipneumococcal capsular polysaccharide
      antibodies by sequential testing of pre- and postvaccination serum samples one
      serotype at a time is sample-intensive and time-consuming and has a relatively
      low throughput. We tested several opsonophagocytic assay (OPA) formats, including
      the reference killing method, a monovalent bacterium-based flow method, a
      trivalent bacterium-based flow method, and a tetravalent bead-based flow method
      using a panel of sera (4 prevaccination and 16 postvaccination, from healthy
      adults immunized with the 23-valent pneumococcal polysaccharide vaccine). The
      trivalent and tetravalent methods allow simultaneous measurements of opsonic
      antibodies to multiple pneumococcal serotypes. The trivalent bacterial-flow OPA
      had significant correlation to the reference OPA method and to a previously
      published flow cytometric OPA (r values ranged from 0.61 to 0.91, P < 0.05) for
      serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. The tetravalent OPA had significant
      correlation to all OPA method formats tested (r values from 0.68 to 0.92, P <
      0.05) for all seven serotypes tested. This tetravalent OPA is an alternative to
      other OPA methods for use during vaccine evaluation and clinical trials. Further,
      the flow cytometric multiplex OPA format has the potential for expansion beyond
      the current four serotypes to eight or more serotypes, which would further
      increase relative sample throughput while reducing reagent and sample volumes
      used.

PMID- 16603614
TI  - Increased levels of Candida albicans mannan-specific T-cell-derived antigen
      binding molecules in patients with invasive candidiasis.
AB  - In addition to cytokines, CD4+ T cells have been found to secrete soluble, T-cell
      derived antigen binding molecules (TABMs). These antigen-specific immunoproteins
      are thought to have immunoregulatory properties in the suppression of cell
      mediated immunity (CMI) because they often associate with interleukin-10 (IL-10)
      and transforming growth factor beta. Decreased CMI causes susceptibility to
      infections caused by organisms which are normally nonpathogenic. In this
      situation, e.g., Candida albicans saprophytism may develop into invasive
      candidiasis. The difficult diagnosis of invasive candidiasis is based on the
      findings obtained from blood cultures and with tissue biopsy specimens, with some
      additional diagnostic value gained by the detection of Candida albicans mannan
      antigenemia and antimannan antibodies. In the present study, Candida albicans
      mannan-specific TABM (CAM-TABM) levels in the sera of patients with invasive
      candidiasis (n = 11), Candida colonization (n = 11) and noncolonization (n = 10),
      recurrent vulvovaginal candidiasis (n = 30), and atopic eczema dermatitis
      syndrome (n = 59) and healthy controls (n = 30) were analyzed. For 14
      participants, the effect of mannan stimulation on TABM production and gamma
      interferon (IFN-gamma) and IL-4 mRNA expression by peripheral blood lymphocytes
      was also studied. It was demonstrated that CAM-TABM production was the highest in
      patients with invasive candidiasis and that CAM-TABM levels could distinguish
      Candida-colonized patients from noncolonized patients. In addition, the CAM-TABM
      level was directly related to mRNA expression for IL-4 but not IFN-gamma. These
      results reinforce the view that TABMs are associated with decreased CMI,
      immunoregulation, and the T-helper cell 2-type immune response.

PMID- 16603615
TI  - High titers of circulating maternal antibodies suppress effector and memory B
      cell responses induced by an attenuated rotavirus priming and rotavirus-like
      particle-immunostimulating complex boosting vaccine regimen.
AB  - We investigated maternal antibody (MatAb) effects on protection and immune
      responses to rotavirus vaccines. Gnotobiotic pigs were injected intraperitoneally
      at birth with pooled serum from sows hyperimmunized with human rotavirus (HRV);
      control pigs received no sow serum. Pigs with or without MatAbs received either
      sequential attenuated HRV (AttHRV) oral priming and intranasal boosting with
      VP2/VP6 virus-like particle (VLP)-immunostimulating complex (ISCOM) (AttHRV/VLP)
      or intranasal VLP-ISCOM prime/boost (VLP) vaccines at 3 to 5 days of age. Subsets
      of pigs were challenged at 28 or 42 days postinoculation with virulent Wa HRV to
      assess protection. Isotype-specific antibody-secreting cell (ASC) responses to
      HRV were quantitated by enzyme-linked immunospot assay to measure effector and
      memory B-cell responses in intestinal and systemic lymphoid tissues pre- and/or
      postchallenge. Protection rates against HRV challenge (contributed by active
      immunity and passive circulating MatAbs) were consistently (but not
      significantly) lower in the MatAb-AttHRV/VLP groups than in the corresponding
      groups without MatAbs. Intestinal B-cell responses in the MatAb-AttHRV/VLP group
      were most suppressed with significantly reduced or no intestinal immunoglobulin A
      (IgA) and IgG effector and memory B-cell responses or antibody titers pre- and
      postchallenge. This suppression was not alleviated but was enhanced after
      extending vaccination/challenge from 28 to 42 days. In pigs vaccinated with
      nonreplicating VLP alone that failed to induce protection, MatAb effects
      differed, with intestinal and systemic IgG ASCs and prechallenge memory B cells
      suppressed but the low intestinal IgA and IgM ASC responses unaffected. Thus, we
      demonstrate that MatAbs differentially affect both replicating and nonreplicating
      HRV vaccines and suggest mechanisms of MatAb interference. This information
      should facilitate vaccine design to overcome MatAb suppression.

PMID- 16603616
TI  - The VR2 epitope on the PorA P1.7-2,4 protein is the major target for the immune
      response elicited by the strain-specific group B meningococcal vaccine MeNZB.
AB  - A protracted epidemic of group B meningococcal disease in New Zealand led to the
      testing of a strain-specific tailor-made vaccine, MeNZB. Immunogenicity levels
      achieved during age group trials enabled New Zealand's regulatory authority to
      grant licensure to deliver MeNZB to all individuals under age 20. During the
      trials target strains for serum bactericidal antibody measurements included the
      vaccine target strain NZ98/254 and two comparator epidemic-type strains (NZ94/167
      and NZ02/09). In this study, 12 other strains differing variously from the
      vaccine strain by their capsular group, PorB type, and PorA variable region
      specificities, or PorA expression, were used as target strains. The PorA
      specificity of the serum bactericidal antibody responses to the vaccine was
      determined for 40 vaccinees. Sets of 10 pre- and postvaccination sera were chosen
      randomly from the young infant, older infant, toddler, and school-age group
      trials. Antibody recognition of linearized PorA proteins was also determined
      using immunoblotting. Across all age groups vaccine-induced serum bactericidal
      antibodies specifically targeted the VR2 P1.4 epitope of the PorA P1.7-2,4
      protein irrespective of the PorB type and/or capsular type of the target strain.
      Deletion of amino acids within the VR2 epitope or replacement of the epitope
      through genetic exchange allowed strains variously to resist antibody-directed
      complement-mediated lysis and negated PorA-specific antibody recognition in
      immunoblots. The demonstration that the immunodominant antibody response was
      specifically for the VR2 P1.4 epitope of the PorA protein supports the public
      health decision to use a strain-specific vaccine for the control of New Zealand's
      epidemic of meningococcal disease.

PMID- 16603617
TI  - Production of soluble triggering receptor expressed on myeloid cells by
      lipopolysaccharide-stimulated human neutrophils involves de novo protein
      synthesis.
AB  - The triggering receptor expressed on myeloid cells (TREM-1) is a recently
      identified receptor expressed on neutrophils and monocytes. Activation of the
      receptor induces neutrophils to release the enzyme myeloperoxidase and
      inflammatory cytokines such as interleukin-8. TREM-1 has an alternatively spliced
      variant that lacks the transmembrane region, resulting in the receptor being
      secreted in a soluble form (sTREM-1). Soluble TREM-1 has been detected in plasma
      during experimental and clinical sepsis and has been advocated as a diagnostic
      marker of infection for pneumonia and as a prognostic marker for patients with
      septic shock. We studied TREM-1 surface expression, using flow cytometry, and
      simultaneously measured sTREM-1 concentrations in culture supernatants of
      lipopolysaccharide (LPS)-stimulated neutrophils. TREM-1 surface expression was
      constitutive and was not upregulated upon LPS stimulation. However, sTREM-1
      release from neutrophils was significantly upregulated by LPS stimulation (P <
      0.0001), an effect that was abrogated by cycloheximide. Soluble TREM-1 is
      therefore secreted by human neutrophils in response to LPS challenge in a process
      involving de novo protein synthesis that is not accompanied by an upregulation of
      the TREM-1 receptor on the surfaces of the cells.

PMID- 16603618
TI  - Abnormal expression and distribution of heat shock protein 90: potential
      etiologic immunoendocrine mechanism of glucocorticoid resistance in idiopathic
      nephrotic syndrome.
AB  - Resistance to glucocorticoid (GC) treatment in some patients with idiopathic
      nephrotic syndrome (INS) is a significant clinical problem. Heat shock protein 90
      (HSP90) is the chaperon protein of the GC receptor, which is supposed to be the
      key factor of GC response. Therefore, we conducted this study to define the
      mechanisms of GC resistance related to HSP90. INS patients and cell lines with
      differing GC responses were included in the present study. We found that the
      level of HSP90 mRNA expression in INS patients was significantly higher than that
      in healthy controls and that HSP90 expression in GC-resistant INS patients was
      higher than that in GC-sensitive INS patients. A confocal immunofluorescence test
      was performed to investigate the subcellular localization of HSP90, and we found
      that the distribution of HSP90 in the GC-resistant INS group was greater in the
      nuclei than that of the GC-sensitive INS group. When the function of HSP90 was
      blocked by the HSP90-specific inhibitor, the GC sensitivity of GC-sensitive cells
      decreased remarkably. These results indicate that HSP90 plays a vital role in GC
      response. In addition, the abnormality in the mRNA level and subcellular
      distribution of HSP90 in GC-resistant INS patients may be etiologically
      significant in terms of endogenous/synthetic GC resistance. On one hand, it may
      disturb immunoendocrine regulation via endogenous GC and immune homeostasis and
      thus be involved in the occurrence of the immune-mediated disease; on the other
      hand, it may influence the patient's response to synthetic GC treatment and
      result in treatment failure.

PMID- 16603619
TI  - Rapid, field-adapted indirect enzyme-linked immunosorbent assay for detection of
      antibodies in bovine whole blood and serum to Brucella abortus.
AB  - A simple, rapid, field-adapted indirect enzyme-linked immunoassay (FldELISA) for
      the detection of antibodies to Brucella abortus in whole blood and serum has been
      developed. This assay detects antibodies to B. abortus in approximately 15 min or
      less. Over a 3-month period, this assay has consistently identified immunized and
      nonimmunized animals, while the percent coefficient of variation for each
      immunized animal has been less than 20%. As with any indirect enzyme-linked
      immunoassay, quality control can be established and maintained. Using defined
      positive and negative sera, the sensitivity and specificity of the FldELISA was
      100% and 94.2%, respectively. As a model, this test can be readily extended to
      other disease applications that use lipopolysaccharide or other stable antigens
      for the detection of antibodies, such as those to Salmonella spp., Escherichia
      coli, or Yersinia spp.

PMID- 16603620
TI  - Immunoglobulin G subclass response to a meningococcal quadrivalent polysaccharide
      diphtheria toxoid conjugate vaccine.
AB  - Changes in the immunoglobulin G1 (IgG1)/IgG2 ratio following vaccination can
      indicate the activation of cellular control mechanisms typical of a T-cell
      dependent response. We examined IgG subclass ratios in 17 healthy adults (26 to
      55 years of age) before and 4 to 6 weeks following immunization with a
      quadrivalent meningococcal-polysaccharide diphtheria toxoid conjugate vaccine
      against serogroups A, C, Y, and W135. Serologic responses were determined by
      serum bactericidal antibody assay and serogroup-specific IgG, IgG1, and IgG2
      enzyme-linked immunosorbent assay. Prevaccination serogroup A-specific IgG1/IgG2
      ratios were <1 for all subjects and differed by subject for C, Y, and W-135.
      Postvaccination, significant increases in IgG, IgG1, and IgG2, were observed for
      all serogroups. Serogroup-specific IgG1/IgG2 ratios increased for group A (14/17
      subjects, 88%), decreased in more than half of subjects for groups C (9/17, 53%)
      and W135 (12/17, 71%) and decreased for serogroup Y (16/17, 94%). IgG1/IgG2
      ratios differed between individual vaccinees and were similar to the responses of
      adults who received pneumococcal conjugate vaccines or a monovalent C conjugate
      vaccine. Further studies on IgG subclasses following meningococcal polysaccharide
      and conjugate vaccination are needed.

PMID- 16603621
TI  - Serological detection of human papillomavirus type 16 infection in human
      immunodeficiency virus (HIV)-positive and high-risk HIV-negative women.
AB  - Serial measurement of antibodies has not been used to provide evidence of active
      viral replication of human papillomavirus (HPV). Serum specimens from sequential
      study visits contributed by 642 human immunodeficiency virus (HIV)-positive and
      116 HIV-negative participants enrolled in the Women's Interagency HIV Study were
      used to detect significant rises in HPV type 16 (HPV-16) antibody levels. Factors
      associated with a significant rise were identified using multivariable logistic
      regression models with generalized estimating equations. Among HIV-positive
      women, 8.3% of 1,997 pairs showed antibody rises, compared to 6.1% of 361 pairs
      among HIV-negative women (P = 0.191). For HIV-positive women, rises were
      associated with current (odds ratio [OR], 23.4; P < 0.001) or past (OR, 8.9; P <
      0.001) HPV-16 infection relative to never being HPV-16 infected and with CD4+
      cell counts (OR per 100-cell increase, 0.8; P < 0.001) but not with sexual
      behavior. For HIV-negative women, rises were associated with past (OR, 10.9; P =
      0.033) HPV-16 infection relative to no HPV-16, current cigarette smoking (OR,
      5.0; P = 0.029) relative to no smoking history, and having 6 to 10 lifetime
      sexual partners compared to 0 to 5 partners (OR, 9.9; P = 0.036). Serial
      measurement of HPV-16 serum antibodies is a useful tool for identifying active
      HPV-16 viral replication. Rises among HIV-positive women may more often result
      from reactivation of a latent HPV infection in the context of HIV-induced
      immunosuppression, while rises among HIV-negative women may more often result
      from reinfection with HPV.

PMID- 16603622
TI  - One-step immunochromatography assay kit for detecting antibodies to canine
      parvovirus.
AB  - This study was performed to determine the feasibility of using whole serum to
      detect antibodies to canine parvovirus (CPV) under nonlaboratory conditions and
      to evaluate the performance characteristics of an immunochromatography assay kit.
      Precise detection of levels of antibody against CPV in puppies can be used to
      determine a vaccination schedule, because maternal antibodies frequently result
      in the failure of protective vaccination, and can also be used to determine the
      antibody levels of infected puppies. Several methods for the titration of CPV
      antibodies have been reported, including the hemagglutination inhibition (HI)
      assay, which is considered the "gold standard." These methods, however, require
      intricate and time-consuming procedures. In this study, a total of 386 serum
      specimens were tested. Compared to the HI assay, the rapid assay had a 97.1%
      sensitivity and a 76.6% specificity (with a cutoff HI titer of 1:80). This single
      step assay could be performed rapidly and easily without special equipment. The
      kit provides a reliable method for detection of anti-CPV antibody where
      laboratory support and personnel are limited.

PMID- 16603624
TI  - ESAT-6 peptide recognition by bovine CD8+ lymphocytes of naturally infected cows
      in herds from southern Italy.
AB  - The aim of this study was to define epitopes of Mycobacterium bovis from ESAT-6
      (early secretory antigen of 6 kDa) recognized by CD8+ T lymphocytes from cows
      naturally infected with Mycobacterium bovis. We found that bovine CD8+ T cells
      recognized 10 out of 11 ESAT-6 peptides tested.

PMID- 16603623
TI  - A decrease in the immunoglobulin G antibody response against the VlsE protein of
      Borrelia burgdorferi sensu lato correlates with the resolution of clinical signs
      in antibiotic-treated patients with early Lyme disease.
AB  - The purpose of this study was to evaluate the diagnostic performance of the
      LIAISON Borrelia Screen (Diasorin, Saluggia, Italy), a new automated immunoassay
      based on the chemiluminescent technology (chemiluminescence immunoassay). To
      assess whether a decrease in a negative value in the anti-VlsE immunoglobulin G
      (IgG) antibody titer was correlated with a positive response to treatment, a
      group of serially collected serum samples from 67 patients with culture-confirmed
      erythema migrans was retrospectively studied. All the patients had been treated
      with antibiotics and were free of disease within 3 to 6 months of follow-up. All
      the 15 patients who were found to be IgG positive at the time of enrollment and
      who were bled at least four times during the follow-up became IgG seronegative at
      2 to 6 months posttreatment. These results indicate that a decline in the anti
      VlsE antibody titer coincides with effective antimicrobial therapy in patients
      with early localized Lyme disease.

PMID- 16603625
TI  - Identification of active site residues of the inverting glycosyltransferase Cgs
      required for the synthesis of cyclic beta-1,2-glucan, a Brucella abortus
      virulence factor.
AB  - Brucella abortus cyclic glucan synthase (Cgs) is a 320-kDa (2868-amino acid)
      polytopic integral inner membrane protein responsible for the synthesis of the
      virulence factor cyclic beta-1,2-glucan by a novel mechanism in which the enzyme
      itself acts as a protein intermediate. Cgs functions as an inverting processive
      beta-1,2-autoglucosyltransferase and has the three enzymatic activities required
      for the synthesis of the cyclic glucan: initiation, elongation, and cyclization.
      To gain further insight into the protein domains that are essential for the
      enzymatic activity, we have compared the Cgs sequence with other
      glycosyltransferases (GTs). This procedure allowed us to identify in the Cgs
      region (475-818) the widely spaced D, DxD, E/D, (Q/R)xxRW motif that is highly
      conserved in the active site of numerous GTs. By site-directed mutagenesis and in
      vitro and in vivo activity assays, we have demonstrated that most of the amino
      acid residues of this motif are essential for Cgs activity. These sequence and
      site-directed mutagenesis analyses also indicate that Cgs should be considered a
      bi-functional modular GT, with an N-terminal GT domain belonging to a new GT
      family related to GT-2 (GT-84) followed by a GH-94 glycoside hydrolase C-terminal
      domain. Furthermore, over-expression of inactive mutants results in wild-type
      (WT) production of cyclic glucan when bacteria co-express the mutant and the WT
      form, indicating that Cgs may function in the membrane as a monomeric enzyme.
      Together, these results are compatible with a single addition model by which Cgs
      acts in the membrane as a monomer and uses the identified motif to form a single
      center for substrate binding and glycosyl-transfer reaction.

PMID- 16603626
TI  - Toward understanding actin activation of myosin ATPase: the role of myosin
      surface loops.
AB  - To understand the complicated interplay when a traveling myosin head reaches
      interaction distance with two actins in a filament we looked to three myosin
      loops that early on exert their influences from the "outside" of the myosin. On
      these we conduct, functionally test, and interpret strategically chosen mutations
      at sites thought from crystallography to be a patch for binding the "first" of
      the two actins. One loop bears a hydrophobic triplet of residues, one is the so
      called "loop 2," and the third is the "cardiomyopathy" loop. So far as we know,
      the myosin sites that first respond are the two lysine-rich loops that produce an
      ionic strength-dependent weak-binding complex with actin. Subsequently, the three
      loops of interest bind the first actin simultaneously, and all three assist in
      closing the cleft in the 50-kDa domain of the myosin, a closure that results in
      transition from weak to strong binding and precedes rapid Pi release and
      motility. Mutational analysis shows that each such loop contact is distinctive in
      the route by which it communicates with its specific target elsewhere in myosin.
      The strongest contact with actin, for example, is that of the triplet-bearing
      loop. On the other hand, that of loop 2 (dependent on drawing close two myosin
      lysines and two actin aspartates) is probably responsible for opening switch I
      and uncovering the gamma-phosphate moiety of bound ATP. Taking into account these
      findings, we begin to arrange in order many molecular events in muscle function.

PMID- 16603627
TI  - The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera
      and predisposes toward erythroid differentiation.
AB  - Although a large proportion of patients with polycythemia vera (PV) harbor a
      valine-to-phenylalanine mutation at amino acid 617 (V617F) in the JAK2 signaling
      molecule, the stage of hematopoiesis at which the mutation arises is unknown.
      Here we isolated and characterized hematopoietic stem cells (HSC) and myeloid
      progenitors from 16 PV patient samples and 14 normal individuals, testing whether
      the JAK2 mutation could be found at the level of stem or progenitor cells and
      whether the JAK2 V617F-positive cells had altered differentiation potential. In
      all PV samples analyzed, there were increased numbers of cells with a HSC
      phenotype (CD34+CD38-CD90+Lin-) compared with normal samples. Hematopoietic
      progenitor assays demonstrated that the differentiation potential of PV was
      already skewed toward the erythroid lineage at the HSC level. The JAK2 V617F
      mutation was detectable within HSC and their progeny in PV. Moreover, the
      aberrant erythroid potential of PV HSC was potently inhibited with a JAK2
      inhibitor, AG490.

PMID- 16603628
TI  - Bispecific abs against modified protein and DNA with oxidized lipids.
AB  - 4-Hydroxy-2-nonenal (HNE), a racemic mixture of 4R- and 4S-enantiomers, is a
      major product of lipid peroxidation and is believed to be largely responsible for
      the cytopathological effects observed during oxidative stress. HNE reacts with
      histidine to form a stable HNE-histidine Michael addition-type adduct possessing
      three chiral centers in the cyclic hemiacetal structure. We have previously
      raised the mAbs, anti-R mAb 310 and anti-S mAb S412, that enantioselectively
      recognized the R-HNE-histidine and R-HNE-histidine adducts, respectively, and
      demonstrated the presence of both epitopes in vivo. In the present study, to
      further investigate the anti-HNE immune response, we analyzed the variable genes
      and primary structure of these Abs and found that the sequence of R310 was highly
      homologous to anti-DNA autoantibodies, the hallmark of systemic lupus
      erythematosus. An x-ray crystallographic analysis of the R310 Fab fragment showed
      that the R-HNE-histidine adduct binds to a hydrophobic pocket in the antigen
      binding site. Despite the structural identity to the anti-DNA autoantibodies,
      however, R310 showed only a slight crossreactivity with the native double
      stranded DNA, whereas the Ab immunoreactivity was dramatically enhanced by the
      treatment of the DNA with 4-oxo-2-nonenal (ONE), an analog of HNE. Moreover, the
      7-(2-oxo-heptyl)-substituted 1,N2-etheno-type ONE-2'-deoxynucleoside adducts were
      identified as alternative epitopes of R310. Molecular mimicry between the R-HNE
      histidine configurational isomers and the ONE-DNA base adducts is proposed for
      the dual crossreactivity.

PMID- 16603629
TI  - Balance between DBT/CKIepsilon kinase and protein phosphatase activities regulate
      phosphorylation and stability of Drosophila CLOCK protein.
AB  - The first circadian-relevant kinase to be identified was DOUBLE-TIME (DBT) in
      Drosophila, a homolog of vertebrate CKIepsilon, which regulates the progressive
      phosphorylation and stability of PERIOD (PER) proteins in animals. A negative
      feedback loop wherein PER directly inhibits the transcriptional activity of the
      CLOCK-CYCLE (CLK-CYC) heterodimer is central to the generation of molecular
      rhythms and normal progression of the clock in Drosophila. We show that DBT
      activity is required for the phase-specific hyperphosphorylation of CLK in vivo,
      an event that correlates with times of maximal repression in per RNA levels. The
      ability of DBT to hyperphosphorylate CLK, enhance its degradation, and evoke
      modest inhibition of CLK-dependent transactivation from circadian promoter
      elements was directly shown in cultured Drosophila cells. Intriguingly, DBT seems
      to function in close partnership with the PER-relevant protein phosphatase 2A,
      resulting in dynamic equilibrium between hypo- and hyperphosphorylated isoforms
      of CLK. This balancing mechanism might act to stabilize the limiting levels of
      CLK against stochastic fluctuations minimizing the propagation of "molecular
      noise" in the feedback circuitry. Also, the subcellular localization of CLK was
      altered from predominately nuclear to strong cytoplasmic staining in the presence
      of PER. These results suggest that, in contrast to mammalian clocks, circadian
      transcriptional inhibition in Drosophila involves displacement of the positive
      factors from chromatin. These results also demonstrate that DBT can target both
      negative and positive factors in circadian feedback loops and support a conserved
      role for dynamic regulation of reversible phosphorylation in directly modulating
      the activities of circadian transcription factors.

PMID- 16603630
TI  - Classic flea-borne transmission does not drive plague epizootics in prairie dogs.
AB  - We lack a clear understanding of the enzootic maintenance of the bacterium
      (Yersinia pestis) that causes plague and the sporadic epizootics that occur in
      its natural rodent hosts. A key to elucidating these epidemiological dynamics is
      determining the dominant transmission routes of plague. Plague can be acquired
      from the bites of infectious fleas (which is generally considered to occur via a
      blocked flea vector), inhalation of infectious respiratory droplets, or contact
      with a short-term infectious reservoir. We present results from a plague modeling
      approach that includes transmission from all three sources of infection
      simultaneously and uses sensitivity analysis to determine their relative
      importance. Our model is completely parameterized by using data from the
      literature and our own field studies of plague in the black-tailed prairie dog
      (Cynomys ludovicianus). Results of the model are qualitatively and quantitatively
      consistent with independent data from our field sites. Although infectious fleas
      might be an important source of infection and transmission via blocked fleas is a
      dominant paradigm in the literature, our model clearly predicts that this form of
      transmission cannot drive epizootics in prairie dogs. Rather, a short-term
      reservoir is required for epizootic dynamics. Several short-term reservoirs have
      the potential to affect the prairie dog system. Our model predictions of the
      residence time of the short-term reservoir suggest that other small mammals,
      infectious prairie dog carcasses, fleas that transmit plague without blockage of
      the digestive tract, or some combination of these three are the most likely of
      the candidate infectious reservoirs.

PMID- 16603631
TI  - The myristoylation of TRIF-related adaptor molecule is essential for Toll-like
      receptor 4 signal transduction.
AB  - TRIF-related adaptor molecule (TRAM) is the fourth Toll/IL-1 resistance domain
      containing adaptor to be described that participates in Toll-like receptor (TLR)
      signaling. TRAM functions exclusively in the TLR4 pathway. Here we show by
      confocal microscopy that TRAM is localized in the plasma membrane and the Golgi
      apparatus, where it colocalizes with TLR4. Membrane localization of TRAM is the
      result of myristoylation because mutation of a predicted myristoylation site in
      TRAM (TRAM-G2A) brought about dissociation of TRAM from the membrane and its
      relocation to the cytosol. Further, TRAM, but not TRAM-G2A, was radiolabeled with
      [3H]myristate in vivo. Unlike wild-type TRAM, overexpression of TRAM-G2A failed
      to elicit either IFN regulatory factor 3 or NF-kappaB signaling. Moreover, TRAM
      G2A was unable to reconstitute LPS responses in bone marrow-derived macrophages
      from TRAM-deficient mice. These observations provide clear evidence that the
      myristoylation of TRAM targets it to the plasma membrane, where it is essential
      for LPS responses through the TLR4 signal transduction pathway, and suggest a
      hitherto unappreciated manner in which LPS responses can be regulated.

PMID- 16603632
TI  - Spatiotemporal control of spindle midzone formation by PRC1 in human cells.
AB  - We have examined the role of PRC1, a midzone-associated, microtubule bundling,
      Cdk substrate protein, in regulating the spatiotemporal formation of the midzone
      in HeLa cells. Cdk-mediated phosphorylation of PRC1 in early mitosis holds PRC1
      in an inactive monomeric state. During the metaphase-to-anaphase transition, PRC1
      is dephosphorylated, promoting PRC1 oligomerization. Using time-lapse video
      microscopy, RNA interference, 3D immunofluorescence reconstruction imaging, and
      rescue experiments, we demonstrate that the dephosphorylated form of PRC1 is
      essential for bundling antiparallel, nonkinetochore, interdigitating microtubules
      to establish the midzone that is necessary for cytokinesis. Our results thus
      indicate that PRC1 is an essential factor in controlling the spatiotemporal
      formation of the midzone in human cells.

PMID- 16603633
TI  - Prospective multicentre study on antibiotic resistance of Helicobacter pylori
      strains obtained from children living in Europe.
AB  - AIM: To prospectively assess the antibacterial resistance rate in Helicobacter
      pylori strains obtained from symptomatic children in Europe. METHODS: During a 4
      year period, 17 paediatric centres from 14 European countries reported
      prospectively on patients infected with H pylori, for whom antibiotic
      susceptibility was tested. RESULTS: A total of 1233 patients were reported from
      Northern (3%), Western (70%), Eastern (9%) and Southern Europe (18%); 41%
      originated from outside Europe as indicated by mother's birth-country; 13% were
      <6 years of age, 43% 6-11 years of age and 44% >11 years of age. Testing was
      carried out before the first treatment (group A, n = 1037), and after treatment
      failure (group B, n = 196). Overall resistance to clarithromycin was detected in
      24% (mean, A: 20%, B: 42%). The primary clarithromycin resistance rate was higher
      in boys (odds ratio (OR) 1.58; 1.12 to 2.24, p = 0.01), in children <6 years
      compared with >12 years (OR 1.82, 1.10 to 3.03, p = 0.020) and in patients living
      in Southern Europe compared with those living in Northern Europe (OR 2.25; 1.52
      to 3.30, p<0.001). Overall resistance rate to metronidazole was 25% (A: 23%, B:
      35%) and higher in children born outside Europe (A: adjusted. OR 2.42, 95% CI:
      1.61 to 3.66, p<0.001). Resistance to both antibiotics occurred in 6.9% (A: 5.3%,
      B: 15.3%). Resistance to amoxicillin was exceptional (0.6%). Children with peptic
      ulcer disease (80/1180, 6.8%) were older than patients without ulcer (p = 0.001).
      CONCLUSION: The primary resistance rate of H pylori strains obtained from
      unselected children in Europe is high. The use of antibiotics for other
      indications seems to be the major risk factor for development of primary
      resistance.

PMID- 16603634
TI  - Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25),
      for the treatment of moderately to severely active ulcerative colitis: a
      randomised, double blind, placebo controlled, dose ranging trial.
AB  - BACKGROUND: An uncontrolled pilot study demonstrated that daclizumab, a humanised
      monoclonal antibody to the interleukin 2 receptor (CD25), might be effective for
      the treatment of active ulcerative colitis. METHODS: A randomised, double blind,
      placebo controlled trial was conducted to evaluate the efficacy of daclizumab
      induction therapy in patients with active ulcerative colitis. A total of 159
      patients with moderate ulcerative colitis were randomised to receive induction
      therapy with daclizumab 1 mg/kg intravenously at weeks 0 and 4, or 2 mg/kg
      intravenously at weeks 0, 2, 4, and 6, or placebo. The primary end point was
      induction of remission at week 8. Remission was defined as a Mayo score of 0 on
      both endoscopy and rectal bleeding components and a score of 0 or 1 on stool
      frequency and physician's global assessment components. Response was defined as a
      decrease from baseline in the Mayo score of at least 3 points. RESULTS: Two per
      cent of patients receiving daclizumab 1 mg/kg (p = 0.11 v placebo) and 7% of
      patients receiving 2 mg/kg (p = 0.73) were in remission at week 8, compared with
      10% of those who received placebo. Response occurred at week 8 in 25% of patients
      receiving daclizumab 1 mg/kg (p = 0.04) and in 33% of patients receiving 2 mg/kg
      (p = 0.30) versus 44% of those receiving placebo. Daclizumab was well tolerated.
      The most frequently reported adverse events in daclizumab treated patients
      compared with placebo treated patients were nasopharyngitis (14.6%) and pyrexia
      (10.7%). CONCLUSION: Patients with moderate ulcerative colitis who are treated
      with daclizumab are not more likely to be in remission or response at eight weeks
      than patients treated with placebo.

PMID- 16603636
TI  - Inflammation, a key event in cancer development.
AB  - Several recent studies have identified nuclear factor-kappaB as a key modulator
      in driving inflammation to cancers. Besides this transcription factor, essential
      in regulating inflammation and cancer development, an inflammatory
      microenvironment inhabiting various inflammatory cells and a network of signaling
      molecules are also indispensable for the malignant progression of transformed
      cells, which is attributed to the mutagenic predisposition of persistent
      infection-fighting agents at sites of chronic inflammation. As a subverted host
      response to inflammation-induced tumors, the inflammatory cells and regulators
      may facilitate angiogenesis and promote the growth, invasion, and metastasis of
      tumor cells. Thus far, research regarding inflammation-associated cancer
      development has focused on cytokines and chemokines as well as their downstream
      targets in linking inflammation and cancer. Moreover, other proteins with
      extensive roles in inflammation and cancer, such as signal transducers and
      activators of transcription, Nrf2, and nuclear factor of activated T cells, are
      also proposed to be promising targets for future studies. The elucidation of
      their specific effects and interactions will accelerate the development of novel
      therapeutic interventions against cancer development triggered by inflammation.

PMID- 16603635
TI  - Why does Japan have a high incidence of gastric cancer? Comparison of gastritis
      between UK and Japanese patients.
AB  - BACKGROUND AND AIMS: The incidence of gastric cancer in Japan is four times
      higher than in the UK. It usually arises in a stomach with corpus predominant or
      pangastritis that has undergone extensive atrophy and intestinal metaplasia. We
      hypothesised that a Japanese population would have a more severe gastritis with a
      corpus predominant or pangastritis pattern and a greater degree of atrophy and
      intestinal metaplasia than that found in the UK. To test this we designed a
      comparative trial. METHODS: A total of 252 age matched consecutive patients were
      recruited from the endoscopy services in Leeds and Tokyo. In each centre, 21
      patients were prospectively selected from each decennial, between the ages of 20
      80 years. All had epigastric discomfort as their predominant symptom. Patients
      with peptic ulcer, cancer, and oesophagitis were excluded. Five gastric biopsies
      were examined by two histopathologists using the updated Sydney system.
      Helicobacter pylori infection was assessed by histology and culture of biopsies
      and enzyme linked immunosorbent assay and immunoblot of plasma. RESULTS:
      Gastritis was found by both pathologists in 59 (47%) UK and 76 (60%) Japanese
      patients (chi(2) test, p = 0.04). In those patients with gastritis, corpus
      predominant or pangastritis was commoner in the Japanese (63% Japan v 36% in the
      UK (chi(2) test, p = 0.003) Atrophy and intestinal metaplasia were more extensive
      and severe (Mann-Whitney U test, p<0.001) and chronic inflammation and polymorph
      activity were also greater, especially in the corpus (Mann-Whitney U test,
      p<0.001). Fifty three of 59 UK gastritis patients (90%) and 67/76 (88%) (chi(2)
      test, p = 1) Japanese gastritis patients were positive for H pylori. Using a
      previously described "gastric cancer risk index" among H pylori positive
      patients, there were significantly more Japanese than UK subjects with a "high
      risk" score. CONCLUSION: In Japanese as opposed to English patients, gastritis is
      more prevalent and severe with more corpus predominant atrophy and intestinal
      metaplasia. These differences may partially explain the higher incidence of
      gastric cancer in Japan.

PMID- 16603637
TI  - Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and
      down-regulation of Xiap in normal and malignant ovarian epithelial cell lines.
AB  - Transforming growth factor-beta superfamily has been implicated in tumorigenesis.
      We have recently shown that Nodal, a member of transforming growth factor-beta
      superfamily, and its receptor, activin receptor-like kinase 7 (ALK7), inhibit
      proliferation and induce apoptosis in human epithelial ovarian cancer cell lines.
      In this study, we further investigated the cellular mechanisms underlying the
      apoptotic action of ALK7 using an immortalized ovarian surface epithelial cell
      line, IOSE397, and an epithelial ovarian cancer cell line, OV2008. Infection of
      these cells with an adenoviral construct carrying constitutively active ALK7 (Ad
      ALK7-ca) potently induced cell death; all cells died after 3 and 5 days of Ad
      ALK7-ca infection in IOSE397 and OV2008 cells, respectively. ALK7-ca induced the
      expression of proapoptotic factor Bax but suppressed the expression of
      antiapoptotic factors Bcl-2, Bcl-XL, and Xiap. Silencing of Bax by small
      interfering RNA in IOSE397 cells significantly reduced ALK7-ca-induced apoptosis
      as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling assay but partially blocked ALK7-ca-induced caspase-3 activation and did
      not affect the down-regulation of Xiap by ALK7-ca. Dominant-negative Smad2,
      Smad3, and Smad4 blocked ALK7-ca-regulated Xiap and Bax expression and caspase-3
      activation. Thus, ALK7-induced apoptosis is at least in part through two Smad
      dependent pathways, Bax/Bcl-2 and Xiap.

PMID- 16603638
TI  - Regulation of class II beta-tubulin expression by tumor suppressor p53 protein in
      mouse melanoma cells in response to Vinca alkaloid.
AB  - The continuous exposure of antimicrotubule drugs to tumors often results in the
      emergence of drug-resistant tumor cells with altered expression of several beta
      tubulin isotypes. We found that Vinca alkaloid enhanced expression of class II
      beta-tubulin isotype (mTUBB2) in mouse B16F10 melanoma cells via alteration of
      the tumor suppressor p53 protein. Vincristine treatment stimulated an increase in
      mTUBB2 mRNA expression and promoted accumulation of this isotype around the
      nuclei. Transient transfection assays employing a reporter construct, together
      with site-directed mutagenesis studies, suggested that the p53-binding site found
      in the first intron was a critical region for mTUBB2 expression. Electrophoretic
      mobility shift assay and associated antibody supershift experiments showed that
      vincristine promoted release of p53 protein from the binding site. In addition,
      exogenous induction of TAp63gamma (p51A), a homologue of p53, canceled the effect
      of vincristine on mTUBB2 expression. These results suggest that p53 protein may
      function as a suppressor of mTUBB2 expression and vincristine-mediated inhibition
      of p53 binding results in enhanced mTUBB2 expression. This phenomenon could be
      related with the emergence of drug-resistant tumor cells induced by Vinca
      alkaloid and may participate in determining the fate of these cells.

PMID- 16603639
TI  - A novel role of DNA polymerase eta in modulating cellular sensitivity to
      chemotherapeutic agents.
AB  - Genetic defects in polymerase eta (pol eta; hRad30a gene) result in xeroderma
      pigmentosum variant syndrome (XP-V), and XP-V patients are sensitive to sunlight
      and highly prone to cancer development. Here, we show that pol eta plays a
      significant role in modulating cellular sensitivity to DNA-targeting anticancer
      agents. When compared with normal human fibroblast cells, pol eta-deficient cells
      derived from XP-V patients were 3-fold more sensitive to beta-d
      arabinofuranosylcytosine, gemcitabine, or cis-diamminedichloroplatinum
      (cisplatin) single-agent treatments and at least 10-fold more sensitive to the
      gemcitabine/cisplatin combination treatment, a commonly used clinical regimen for
      treating a wide spectrum of cancers. Cellular and biochemical analyses strongly
      suggested that the higher sensitivity of XP-V cells to these agents was due to
      the inability of pol eta-deficient cells to help resume the DNA replication
      process paused by the gemcitabine/cisplatin-introduced DNA lesions. These results
      indicated that pol eta can play an important role in determining the cellular
      sensitivity to therapeutic agents. The findings not only illuminate pol eta as a
      potential pharmacologic target for developing new anticancer agents but also
      provide new directions for improving future chemotherapy regimen design
      considering the use of nucleoside analogues and cisplatin derivatives.

PMID- 16603640
TI  - Gene promoter hypermethylation in mouse lung tumors.
AB  - The mouse is a good model for evaluating the efficacy of chemopreventive agents
      for lung cancer. Gene silencing by promoter hypermethylation is a critical
      component for the development and progression of lung cancer and an emerging
      target for preventive intervention by demethylating agents. Genes methylated in
      mouse lung tumors could serve as biomarkers to evaluate the effectiveness of
      demethylating agents for preventing lung cancer and causing gene reexpression in
      vivo. The purpose of the current study was to evaluate a panel of genes
      inactivated by promoter hypermethylation in human lung cancer for silencing by
      this epigenetic mechanism in murine lung tumors induced by 4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanone (NNK), cigarette smoke, or arising spontaneously.
      Cadherin-13, estrogen receptor-alpha, progesterone receptor, and runt-related
      transcription factor-3 were frequently methylated in mouse lung tumor-derived
      cell lines, whereas cadherin-1 and suppressor of cytokine signaling-1 were not.
      Methylation within these four genes was associated with lack of expression that
      could be restored after treatment with 5-aza-2'-deoxycytidine and with
      methylation within the CpG island of each gene. Methylation-specific PCR revealed
      that methylation of these four genes occurred at prevalences of 24% to 69% in
      primary lung tumors arising spontaneously or induced by exposure to cigarette
      smoke or NNK. Estrogen receptor-alpha methylation was more frequent in
      spontaneously occurring lung cancer than cigarette smoke-induced or NNK-induced
      lung cancer, whereas runt-related transcription factor-3 showed the opposite
      relationship. Thus, genes can be targeted for inactivation by methylation,
      depending on exposure history. This study indicates that methylation events
      frequently observed in human lung cancer are recapitulated in the mouse model and
      identifies four potential biomarkers for assessing intervention approaches for
      reversing epigenetically mediated gene silencing.

PMID- 16603641
TI  - 1'-Acetoxychavicol acetate inhibits RANKL-induced osteoclastic differentiation of
      RAW 264.7 monocytic cells by suppressing nuclear factor-kappaB activation.
AB  - Osteoclastogenesis is commonly associated with various age-related diseases,
      including cancer. A member of the tumor necrosis factor superfamily, receptor
      activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL), has been shown to
      play a critical role in osteoclast formation and bone resorption. Thus, agents
      that suppress RANKL signaling have a potential to suppress bone loss. In this
      report, we investigated the effect of 1'-acetoxychavicol acetate (ACA), a
      component of Alpina galanga, on RANKL signaling and consequent osteoclastogenesis
      in RAW 264.7 cells, a murine monocytic cell line. Treatment of these cells with
      RANKL activated NF-kappaB, and coexposure of the cells to ACA completely
      suppressed RANKL-induced NF-kappaB activation in a time- and concentration
      dependent manner. The suppression of NF-kappaB by ACA was mediated through
      suppression of RANKL-induced activation of IkappaBalpha kinase, IkappaBalpha
      phosphorylation, and IkappaBalpha degradation. Furthermore, incubation of
      monocytic cells with RANKL induced osteoclastogenesis, and ACA suppressed it.
      Inhibition of osteoclastogenesis was maximal when cells were simultaneously
      exposed to ACA and RANKL and minimum when ACA was added 2 days after RANKL. ACA
      also inhibited the osteoclastogenesis induced by human breast cancer MCF-7 cells,
      multiple myeloma MM1 cells, and head and neck squamous cell carcinoma LICR-LON
      HN5 cells. These results indicate that ACA is an effective blocker of RANKL
      induced NF-kappaB activation and of osteoclastogenesis induced by RANKL and tumor
      cells, suggesting its potential as a therapeutic agent for osteoporosis and
      cancer-associated bone loss.

PMID- 16603642
TI  - Frequent IGF2/H19 domain epigenetic alterations and elevated IGF2 expression in
      epithelial ovarian cancer.
AB  - Overexpression of the imprinted insulin-like growth factor-II (IGF2) is a
      prominent characteristic of gynecologic malignancies. The purpose of this study
      was to determine whether IGF2 loss of imprinting (LOI), aberrant H19 expression,
      and/or epigenetic deregulation of the IGF2/H19 imprinted domain contributes to
      elevated IGF2 expression in serous epithelial ovarian tumors. IGF2 LOI was
      observed in 5 of 23 informative serous epithelial ovarian cancers, but this did
      not correlate with elevated expression of IGF2 H19 RNA expression levels were
      also found not to correlate with IGF2 transcript levels. However, we identified
      positive correlations between elevated IGF2 expression and hypermethylation of
      CCCTC transcription factor binding sites 1 and 6 at the H19 proximal imprint
      center (P = 0.05 and 0.02, respectively). Hypermethylation of CCCTC transcription
      factor sites 1 and 6 was observed more frequently in cancer DNA compared with
      lymphocyte DNA obtained from women without malignancy (P < 0.0001 for both sites
      1 and 6). Ovarian cancers were also more likely to exhibit maternal allele
      specific hypomethylation upstream of the imprinted IGF2 promoters when compared
      with normal lymphocyte DNA (P = 0.004). This is the same region shown previously
      to be hypomethylated in colon cancers with IGF2 LOI, but this was not associated
      with LOI in ovarian cancers. Elevated IGF2 expression is a frequent event in
      serous ovarian cancer and this occurs in the absence of IGF2 LOI. These data
      indicate that the epigenetic changes observed in these cancers at the imprint
      center may contribute to IGF2 overexpression in a novel mechanistic manner.

PMID- 16603643
TI  - Antimicrobial activity of DW-224a, a new fluoroquinolone, against Streptococcus
      pneumoniae.

PMID- 16603644
TI  - Phenotypic and genotypic characterization of antimicrobial resistance in
      Escherichia coli O111 isolates.
AB  - OBJECTIVES: The aim of this study was to generate baseline data on the prevalence
      and molecular basis of antimicrobial resistance in Escherichia coli O111
      isolates. METHODS: A total of 105 epidemiologically unrelated E. coli O111
      isolates from humans and cattle (isolated between 1983 and 2003) were tested for
      susceptibility to 17 antimicrobial agents by broth microdilution. Resistant
      isolates were screened by molecular methods for resistance genes, class 1 and 2
      integrons and mutations in the quinolone-resistance determining regions. RESULTS:
      Resistance was found in 76% of the isolates, with a prevalence of 72% for
      multiresistance. The most prevalent resistances were to streptomycin,
      sulfamethoxazole and tetracycline (72-68%), followed by spectinomycin, ampicillin
      and kanamycin/neomycin (39-25%). For each antimicrobial agent, the predominant
      resistance genes were ampicillin, bla(TEM) (94%); chloramphenicol, catA1 (100%);
      gentamicin, aac(3)-IV and aac(3)-II (50% each); kanamycin, aphA1 (100%);
      streptomycin, aadA1- like (66%); sulfamethoxazole, sul1 (59%); tetracycline,
      tet(A) (86%); and trimethoprim, dfrA1-like (83%). Class 1 integrons were found in
      41% of the isolates. They carried aadA1, dfrA1-aadA1 and dfrA15-aadA1. A class 2
      integron (dfrA1-sat1-aadA1) was found in one isolate. Only three isolates (3%)
      were resistant to nalidixic acid (reduced susceptibility to ciprofloxacin), with
      a single mutation in the gyrA gene. CONCLUSIONS: E. coli O111 strains exhibit a
      wide repertoire of genetic elements to sustain antimicrobial pressure. Two
      specific antimicrobial resistance pheno/genotypes, [STR-SPT]-SUL-TET/aadA1-sul1
      tet(A) and STR-SUL-TET-AMP-[KAN-NEO]/strA/B-sul2-tet(A)-bla(TEM)-aphA1, are
      predominant.

PMID- 16603645
TI  - High prevalence of isolated tumour cells in regional lymph nodes from pN0
      colorectal cancer.
AB  - BACKGROUND: The prevalence of isolated tumour cells (ITCs) in regional lymph
      nodes from colorectal cancer (CRC) is controversial and has never been
      prospectively assessed in large groups of consecutive patients. pN0 early
      relapsing CRC can be explained by lymph node-ITC. AIM: To assess the prevalence
      of ITCs in regional lymph nodes from 309 consecutive patients with pN0M0
      (pathological (p)-tumour-node-metastasis (TNM) staging system) CRCs. PATIENTS AND
      METHODS: ITCs were assessed by immunohistochemistry (MNF116 monoclonal antibody
      (1:100); Dako, Glostrup, Denmark) in two serial histological sections obtained
      from 5016 mesenteric lymph nodes from 309 patients with pN0 CRCs (mean number of
      lymph nodes per patient = 16.2; p-TNM stage 0, n = 25; p-TNM stage I, n = 123;
      and p-TNM stage II (A+B), n = 161). Tumour histology, vascular cancer invasion
      and pathological stage were also recorded. RESULTS: ITCs were detected in the
      regional lymph nodes of 156 of 309 (50.5%) patients with CRC, mostly in nodes
      located within 3 cm from the neoplasia. ITC status correlated with (a) tumour p
      TNM stage (Pearson's chi(2): p<0; ordered logistic regression: odds ratio (OR) =
      4.6; 95% confidence interval (CI) = 2.88 to 7.33; p<0) and (b) pT value
      (Pearson's chi(2): p = 0; ordered logistic regression: OR = 4.9; 95% CI = 3.1 to
      7.7; p<0). By multivariate analysis, including p-TNM stage, vascular invasion and
      ITC status, both stage (OR = 5.1; 95% CI = 2.9 to 8.9; p<0) and vascular invasion
      (OR = 4.2; 95% CI = 1.94 to 8.98; p<0) were found to be independent variables
      associated with ITC+ lymph nodes. CONCLUSION: More than 50% of pN0-CRC patients
      have ITCs in the mesenteric lymph nodes. ITC status is significantly correlated
      with cancer stage and vascular cancer invasion. The clinicopathological effect of
      ITC remains to be prospectively evaluated.

PMID- 16603646
TI  - Nuclear morphometry in columnar cell lesions of the breast: is it useful?
AB  - AIMS: To evaluate the nuclear morphometric features of breast columnar cell
      lesions (CCLs) observed on mammotome core biopsies, to determine if there are
      significant measurable differences between those with atypia and those without.
      Correlation with follow-up open excision specimens was made. METHODS: Mammotome
      core biopsies performed on patients that contained CCLs were derived from the
      departmental case files. Histological material was reviewed and foci of CCLs
      demarcated for nuclear morphometric assessment, which was accomplished using an
      imaging system. Nuclear parameters studied were nuclear area and perimeter,
      circularity factor and feret's diameter. Statistical analysis used the GraphPad
      Prism software, with p<0.05 indicating significance. RESULTS: On examination of
      core biopsies of 40 patients with CCLs, 8 lesions were benign, 4 showed atypical
      lobular hyperplasia, 8 showed CCLs with nuclear atypia, 19 disclosed atypical
      ductal hyperplasia (ADH) and 1 showed ductal carcinoma in situ (DCIS). The
      nuclear area, perimeter and feret's diameter of CCLs with atypia were
      significantly greater than those without (p = 0.04, 0.03 and 0.019,
      respectively), whereas no difference was observed in the circularity factor.
      Follow-up open excision biopsy specimens in 24 patients showed upgrading to DCIS
      in 40% of cases diagnosed initially with ADH on core biopsy compared with 20% of
      CCLs with atypia. CONCLUSIONS: Nuclear morphometry in CCLs confirms nuclear size
      as the key parameter in the assessment of nuclear atypia. Whether it can be
      potentially used as an adjunctive tool depends on the establishment of
      appropriate cut-offs.

PMID- 16603647
TI  - Weight correction of MoM values: which method?
AB  - BACKGROUND: Adjusting maternal serum markers for maternal weight is considered to
      be a standard practice when screening for pregnancies associated with Down's
      syndrome. The choice of model for taking maternal weight into account is,
      however, rarely explicitly evaluated. METHOD: The relationship between the
      maternal serum markers alphafetoprotein (AFP), human chorionic gonadotropin (HCG)
      and unconjugated oestriol (uE3), determined with the Beckman Coulter access
      reagents and maternal weight was investigated in a cohort of 752 Belgian women
      being screened for pregnancy associated with Down's syndrome. Two different
      models (the log-linear equation and the linear-reciprocal equation) were used to
      determine the relationship between the serum markers and maternal weight.
      RESULTS: A significant relationship between log(10) multiples of median (MoM)
      values and weight (kg) was obtained for all markers, and the log-linear model had
      higher coefficients of determination (r(2)) when compared with the linear
      reciprocal model. Weight correction with either method achieved the optimum
      effect that the correction factor for a woman with a population median weight of
      65.5 kg was not significantly different from 1. Simulated weight-corrected MoM
      values with the two approaches were compared and variation was estimated. The
      mean difference between the weight-corrected MoM values calculated by the two
      methods was 7.8% (SD 4.3%) for AFP, 14.0% (4.4%) for HCG and 5.9% (3.2%) for uE3.
      This resulted in a difference in risk estimate of 1.66-5.34% for Down's syndrome
      owing to weight correction algorithm differences in women of median weight.
      CONCLUSION: The log-linear weight correction approach was shown to be marginally
      more effective by a goodness-of-fit analysis. Differences in weight-corrected MoM
      values estimated with the two approaches are highly significant (p<0.0001,
      Wilcoxon's paired sample test), but the effect on risk calculation was not
      significant. It was observed that the changes in risk became significant the more
      the MoM correction factors deviated from 1.

PMID- 16603648
TI  - Use of rapid diagnostic tests for diagnosis of malaria in the UK.
AB  - BACKGROUND: Malaria is currently diagnosed almost exclusively by microscopy in
      clinical laboratories. The introduction of rapid diagnostic tests (RDTs) may be
      useful in achieving rapid detection of malaria parasites, especially in
      situations where malaria is not often seen or where staff are inexperienced. AIM:
      To explore the use of RDT in UK laboratories. METHODS: The current use of RDTs
      was surveyed in UK laboratories subscribing to the United Kingdom National
      External Quality Assessment Scheme blood parasitology and haematology schemes.
      RESULTS: An overall survey response rate of 60.3% was seen. RDTs were found to be
      the preferred choice, either alone or in conjunction with microscopy in 31.2% of
      the samples examined during normal working hours and in 44.3% of the specimens
      examined on call. CONCLUSIONS: During on-call hours, the use of RDTs was observed
      to increase and RDTs changed the diagnosis in 12% of laboratories. No established
      protocol for RDT use was, however, observed in the UK. A protocol that needs to
      be validated in the laboratory setting is suggested.

PMID- 16603649
TI  - Distinction between hereditary and sporadic breast cancer on the basis of
      clinicopathological data.
AB  - BACKGROUND: About 5% of all breast cancer cases are attributable to germline
      mutations in BRCA1 or BRCA2 genes. BRCA mutations in suspected carriers, however,
      may be missed, which hampers genetic counselling. MATERIALS AND METHODS:
      Different clinicopathological features were compared between 22 breast cancers
      from carriers of proved BRCA1 mutations and 604 cancers from sporadic controls.
      In addition, 5 BRCA2-related breast cancers and 66 breast cancers of untested
      patients at intermediate risk and 19 breast cancers of untested patients at high
      risk of hereditary disease on the basis of family history were evaluated.
      RESULTS: A "probably sporadic" class (age >or=54 years and epidermal growth
      factor receptor (EGFR) negative; 68% of cases) with a 0% chance of BRCA1-related
      breast cancer containing 79% of the sporadic cases was yielded by using a
      decision tree with age, Ki67 and EGFR. A 75% chance of BRCA1-related breast
      cancer was shown by the "probably BRCA1-related" class (age <54 years and Ki67
      >or=25%; 8% of cases) with 82% of the BRCA1-related cases but only 1.4% of the
      sporadic cases. Most cases at intermediate or high risk of hereditary disease on
      the basis of family history could be classified with high probability as either
      probably BRCA1 related or probably sporadic. CONCLUSION: Breast carcinomas can be
      classified with a high level of certainty as sporadic or related to BRCA1
      germline mutations by using a decision tree with age, Ki67 and EGFR. This can be
      clinically useful in mutation analysis in families with a borderline risk of
      hereditary disease.

PMID- 16603650
TI  - Hsulf-1 regulates growth and invasion of pancreatic cancer cells.
AB  - BACKGROUND: Hsulf-1 is a newly identified enzyme with arylsulphatase activity
      that can regulate the sulphation state of cell-surface heparan sulphate
      proteoglycans (HSPGs). In vitro overexpression of this enzyme in pancreatic
      cancer cells decreases responsiveness to fibroblastic growth factor-2, as Hsulf-1
      is up regulated in primary pancreatic adenocarcinoma. AIM: To further analyse the
      functions of the Hsulf-1 enzyme in vitro and in vivo with respect to growth,
      invasion and tumorigenicity. METHODS AND RESULTS: Transfection of Panc-1
      pancreatic cancer cells with a full-length Hsulf-1 expression vector resulted in
      increased invasiveness and adhesiveness. An in vivo xenograft nude mouse tumour
      model showed a markedly reduced growth potential of Hsulf-1-expressing Panc-1
      cells, which correlated with a considerably lower proliferation rate. Hsulf-1
      positive nude mouse tumours showed better development of interstitial matrix
      structures, with increased blood vessel density in these tumours. In an
      orthotopic model, Hsulf-1-positive tumours exhibited enhanced local invasiveness.
      In human primary pancreatic cancers there was strong staining for sulphated
      HSPGs, which was markedly reduced in metastatic tissue samples. CONCLUSION: Hsulf
      1-mediated desulphation of HSPGs reduces the growth ability of Panc-1 pancreatic
      cancer cells, but increases the basal invasiveness of these cells, suggesting an
      important role of this enzyme in pancreatic cancer progression.

PMID- 16603651
TI  - Endogenous and synthetic microRNAs stimulate simultaneous, efficient, and
      localized regulation of multiple targets in diverse species.
AB  - Recent studies demonstrated that pattern formation in plants involves regulation
      of transcription factor families by microRNAs (miRNAs). To explore the potency,
      autonomy, target range, and functional conservation of miRNA genes, a systematic
      comparison between plants ectopically expressing pre-miRNAs and plants with
      corresponding multiple mutant combinations of target genes was performed. We show
      that regulated expression of several Arabidopsis thaliana pre-miRNA genes induced
      a range of phenotypic alterations, the most extreme ones being a phenocopy of
      combined loss of their predicted target genes. This result indicates quantitative
      regulation by miRNA as a potential source for diversity in developmental
      outcomes. Remarkably, custom-made, synthetic miRNAs vectored by endogenous pre
      miRNA backbones also produced phenocopies of multiple mutant combinations of
      genes that are not naturally regulated by miRNA. Arabidopsis-based endogenous and
      synthetic pre-miRNAs were also processed effectively in tomato (Solanum
      lycopersicum) and tobacco (Nicotiana tabacum). Synthetic miR-ARF targeting Auxin
      Response Factors 2, 3, and 4 induced dramatic transformations of abaxial tissues
      into adaxial ones in all three species, which could not cross graft joints.
      Likewise, organ-specific expression of miR165b that coregulates the PHABULOSA
      like adaxial identity genes induced localized abaxial transformations. Thus,
      miRNAs provide a flexible, quantitative, and autonomous platform that can be
      employed for regulated expression of multiple related genes in diverse species.

PMID- 16603652
TI  - Dynamic and compensatory responses of Arabidopsis shoot and floral meristems to
      CLV3 signaling.
AB  - In Arabidopsis thaliana, the stem cell population of the shoot system is
      controlled by regulatory circuitry involving the WUSCHEL (WUS) and CLAVATA (CLV1
      3) genes. WUS signals from the organizing center (OC) to promote stem cell fate
      at the meristem apex. Stem cells express the secreted peptide CLV3 that activates
      a signal transduction cascade to restrict WUS expression, thus providing a
      feedback mechanism. Stem cell homeostasis is proposed to be achieved by balancing
      these signals. We tested the dynamics of CLV3 signaling using an inducible gene
      expression system. We show here that increasing the CLV3 signal can very rapidly
      repress WUS expression during development, which in turn causes a fast reduction
      of CLV3 expression. We demonstrate that increased CLV3 signaling restricts
      meristem growth and promotes allocation of peripheral meristem cells into organ
      primordia. In addition, we extend the current model for stem cell control by
      showing that meristem homeostasis tolerates variation in CLV3 levels over a 10
      fold range and that high-level CLV3 signaling can be partially compensated with
      time, indicating that the level of CLV3 expression communicates only limited
      information on stem cell number to the underlying OC cells.

PMID- 16603653
TI  - Gamma-tubulin is essential for acentrosomal microtubule nucleation and
      coordination of late mitotic events in Arabidopsis.
AB  - Gamma-tubulin is required for microtubule (MT) nucleation at MT organizing
      centers such as centrosomes or spindle pole bodies, but little is known about its
      noncentrosomal functions. We conditionally downregulated gamma-tubulin by
      inducible expression of RNA interference (RNAi) constructs in Arabidopsis
      thaliana. Almost complete RNAi depletion of gamma-tubulin led to the absence of
      MTs and was lethal at the cotyledon stage. After induction of RNAi expression,
      gamma-tubulin was gradually depleted from both cytoplasmic and microsomal
      fractions. In RNAi plants with partial loss of gamma-tubulin, MT recovery after
      drug-induced depolymerization was impaired. Similarly, immunodepletion of gamma
      tubulin from Arabidopsis extracts severely compromised in vitro polymerization of
      MTs. Reduction of gamma-tubulin protein levels led to randomization and bundling
      of cortical MTs. This finding indicates that MT-bound gamma-tubulin is part of a
      cortical template guiding the microtubular network and is essential for MT
      nucleation. Furthermore, we found that cells with decreased levels of gamma
      tubulin could progress through mitosis, but cytokinesis was strongly affected.
      Stepwise diminution of gamma-tubulin allowed us to reveal roles for MT nucleation
      in plant development, such as organization of cell files, anisotropic and polar
      tip growth, and stomatal patterning. Some of these functions of gamma-tubulin
      might be independent of MT nucleation.

PMID- 16603654
TI  - Physical and functional interactions between pathogen-induced Arabidopsis WRKY18,
      WRKY40, and WRKY60 transcription factors.
AB  - Limited information is available about the roles of specific WRKY transcription
      factors in plant defense. We report physical and functional interactions between
      structurally related and pathogen-induced WRKY18, WRKY40, and WRKY60
      transcription factors in Arabidopsis thaliana. The three WRKY proteins formed
      both homocomplexes and heterocomplexes and DNA binding activities were
      significantly shifted depending on which WRKY proteins were present in these
      complexes. Single WRKY mutants exhibited no or small alterations in response to
      the hemibiotrophic bacterial pathogen Pseudomonas syringae and the necrotrophic
      fungal pathogen Botrytis cinerea. However, wrky18 wrky40 and wrky18 wrky60 double
      mutants and the wrky18 wrky40 wrky60 triple mutant were substantially more
      resistant to P. syringae but more susceptible to B. cinerea than wild-type
      plants. Thus, the three WRKY proteins have partially redundant roles in plant
      responses to the two distinct types of pathogens, with WRKY18 playing a more
      important role than the other two. The contrasting responses of these WRKY
      mutants to the two pathogens correlated with opposite effects on pathogen-induced
      expression of salicylic acid-regulated PATHOGENESIS-RELATED1 and jasmonic acid
      regulated PDF1.2. While constitutive expression of WRKY18 enhanced resistance to
      P. syringae, its coexpression with WRKY40 or WRKY60 made plants more susceptible
      to both P. syringae and B. cinerea. These results indicate that the three WRKY
      proteins interact both physically and functionally in a complex pattern of
      overlapping, antagonistic, and distinct roles in plant responses to different
      types of microbial pathogens.

PMID- 16603655
TI  - PH4 of Petunia is an R2R3 MYB protein that activates vacuolar acidification
      through interactions with basic-helix-loop-helix transcription factors of the
      anthocyanin pathway.
AB  - The Petunia hybrida genes ANTHOCYANIN1 (AN1) and AN2 encode transcription factors
      with a basic-helix-loop-helix (BHLH) and a MYB domain, respectively, that are
      required for anthocyanin synthesis and acidification of the vacuole in petal
      cells. Mutation of PH4 results in a bluer flower color, increased pH of petal
      extracts, and, in certain genetic backgrounds, the disappearance of anthocyanins
      and fading of the flower color. PH4 encodes a MYB domain protein that is
      expressed in the petal epidermis and that can interact, like AN2, with AN1 and
      the related BHLH protein JAF13 in yeast two-hybrid assays. Mutation of PH4 has
      little or no effect on the expression of structural anthocyanin genes but
      strongly downregulates the expression of CAC16.5, encoding a protease-like
      protein of unknown biological function. Constitutive expression of PH4 and AN1 in
      transgenic plants is sufficient to activate CAC16.5 ectopically. Together with
      the previous finding that AN1 domains required for anthocyanin synthesis and
      vacuolar acidification can be partially separated, this suggests that AN1
      activates different pathways through interactions with distinct MYB proteins.

PMID- 16603657
TI  - Remodeling of astrocytes, a prerequisite for synapse turnover in the adult brain?
      Insights from the oxytocin system of the hypothalamus.
AB  - Neurons, including their synapses, are generally ensheathed by fine processes of
      astrocytes, but this glial coverage can be altered under different physiological
      conditions that modify neuronal activity. Changes in synaptic connectivity
      accompany astrocytic transformations so that an increased number of synapses are
      associated with reduced astrocytic coverage of postsynaptic elements, whereas
      synaptic numbers are reduced on reestablishment of glial coverage. A system that
      exemplifies activity-dependent structural synaptic plasticity in the adult brain
      is the hypothalamo-neurohypophysial system, and in particular, its oxytocin
      component. Under strong, prolonged activation (parturition, lactation, chronic
      dehydration), extensive portions of somatic and dendritic surfaces of
      magnocellular oxytocin neurons are freed of intervening astrocytic processes and
      become directly juxtaposed. Concurrently, they are contacted by an increased
      number of inhibitory and excitatory synapses. Once stimulation is over,
      astrocytic processes again cover oxytocinergic surfaces and synaptic numbers
      return to baseline levels. Such observations indicate that glial ensheathment of
      neurons is of consequence to neuronal function, not only directly, for example by
      modifying synaptic transmission, but indirectly as well, by preparing neuronal
      surfaces for synapse turnover.

PMID- 16603658
TI  - Point: Heat-induced membrane depolarization of hypothalamic neurons: a putative
      mechanism of central thermosensitivity.

PMID- 16603656
TI  - Renal autoregulation: new perspectives regarding the protective and regulatory
      roles of the underlying mechanisms.
AB  - When the kidney is subjected to acute increases in blood pressure (BP), renal
      blood flow (RBF) and glomerular filtration rate (GFR) are observed to remain
      relatively constant. Two mechanisms, tubuloglomerular feedback (TGF) and the
      myogenic response, are thought to act in concert to achieve a precise moment-by
      moment regulation of GFR and distal salt delivery. The current view is that this
      mechanism insulates renal excretory function from fluctuations in BP. Indeed, the
      concept that renal autoregulation is necessary for normal renal function and
      volume homeostasis has long been a cornerstone of renal physiology. This article
      presents a very different view, at least regarding the myogenic component of this
      response. We suggest that its primary purpose is to protect the kidney against
      the damaging effects of hypertension. The arguments advanced take into
      consideration the unique properties of the afferent arteriolar myogenic response
      that allow it to protect against the oscillating systolic pressure and the
      accruing evidence that when this response is impaired, the primary consequence is
      not a disturbed volume homeostasis but rather an increased susceptibility to
      hypertensive injury. It is suggested that redundant and compensatory mechanisms
      achieve volume regulation, despite considerable fluctuations in distal delivery,
      and the assumed moment-by-moment regulation of renal hemodynamics is questioned.
      Evidence is presented suggesting that additional mechanisms exist to maintain
      ambient levels of RBF and GFR within normal range, despite chronic alterations in
      BP and severely impaired acute responses to pressure. Finally, the implications
      of this new perspective on the divergent roles of the myogenic response to
      pressure vs. the TGF response to changes in distal delivery are considered, and
      it is proposed that in addition to TGF-induced vasoconstriction, vasodepressor
      responses to reduced distal delivery may play a critical role in modulating
      afferent arteriolar reactivity to integrate the regulatory and protective
      functions of the renal microvasculature.

PMID- 16603659
TI  - Severe pulmonary embolism:pulmonary artery clot load scores and cardiovascular
      parameters as predictors of mortality.
AB  - PURPOSE: To retrospectively evaluate pulmonary artery (PA) clot load scores and
      computed tomographic (CT) cardiovascular parameters as predictors of mortality in
      patients with severe pulmonary embolism (PE). MATERIALS AND METHODS:
      Institutional review board approval was obtained with waiver of informed consent.
      A total of 82 consecutive patients (42 women, 40 men; mean age+/-standard
      deviation, 61 years+/-15) were admitted to the intensive care unit for PE-related
      conditions and were evaluated by using CT pulmonary angiography. Two independent
      readers who were blinded to clinical outcome quantified PA clot load by using
      four scoring systems. Cardiovascular measurements included right ventricular (RV)
      and left ventricular (LV) short-axis measurements; RV short axis to LV short axis
      (RV/LV) ratios; main PA, ascending aorta, azygos vein, and superior vena cava
      diameters; and main PA diameter to aorta diameter ratios. Reflux of contrast
      medium into the inferior vena cava, leftward bowing of the interventricular
      septum, pleural or pericardial effusion, pulmonary consolidation, infarct,
      platelike atelectasis, and mosaic ground-glass opacity were also recorded.
      Results were correlated with patient outcome during hospital stay by using the
      Wilcoxon rank sum and chi2 tests. RESULTS: Twelve patients died within 1-14 days.
      RV and LV short axis; RV/LV ratio; azygos vein, superior vena cava, and aorta
      diameters; and contrast medium reflux into the inferior vena cava were
      significantly different between survivors and nonsurvivors (P<.05). No
      significant relationship was found between PA clot load and mortality rate. RV/LV
      ratio and azygos vein diameter allowed correct prediction of survival in 89% of
      patients (P<.001). CONCLUSION: RV/LV ratio and azygos vein diameter are
      predictors of mortality in patients with severe PE.

PMID- 16603660
TI  - Proton MR spectroscopy with choline peak as malignancy marker improves positive
      predictive value for breast cancer diagnosis: preliminary study.
AB  - PURPOSE: To prospectively evaluate the diagnostic performance of magnetic
      resonance (MR) spectroscopy in patients with suspicious lesions or biopsy-proved
      cancers at MR imaging by using histologic findings as the reference standard.
      MATERIALS AND METHODS: After institutional review board approval and informed
      consent were obtained for this HIPAA-compliant study, breast MR spectroscopy was
      performed in patients with suspicious or biopsy-proved malignant lesions
      measuring 1 cm or larger at MR imaging. Single-voxel MR spectroscopy data were
      collected from a single rectangular volume of interest that encompassed the
      lesion. MR spectroscopy findings were defined as positive if the signal-to-noise
      ratio of the choline resonance peak was greater than or equal to 2 and as
      negative in all other cases. MR spectroscopy findings were then compared with
      histologic findings. RESULTS: A total of 56 patients (age range, 20-77 years)
      with 57 lesions were imaged. The median lesion size at MR imaging was 2.3 cm
      (range, 1-15 cm). Histologically, 31 (54%) of 57 lesions were malignant, and 26
      (46%) were benign. A choline peak was present in 34 of 57 lesions (including all
      cancers) and in three of 26 benign lesions, giving MR spectroscopy a sensitivity
      of 100% and a specificity of 88%. In 40 lesions of unknown histologic type, the
      use of MR spectroscopy as an adjunct to MR imaging would have significantly
      (P<.01) increased the positive predictive value of biopsy from 35% to 82%. If
      biopsy had been performed only on those lesions with a choline peak at MR
      spectroscopy, biopsy may have been spared in 23 (58%) of 40 lesions, and none of
      the cancers would have been missed. CONCLUSION: Proton MR spectroscopy was
      successfully incorporated into breast MR imaging studies for lesions measuring 1
      cm or larger. This technique may be useful in reducing the number of lesions
      detected at MR imaging that require biopsy.

PMID- 16603662
TI  - Transcriptomic footprints disclose specificity of reactive oxygen species
      signaling in Arabidopsis.
AB  - Reactive oxygen species (ROS) are key players in the regulation of plant
      development, stress responses, and programmed cell death. Previous studies
      indicated that depending on the type of ROS (hydrogen peroxide, superoxide, or
      singlet oxygen) or its subcellular production site (plastidic, cytosolic,
      peroxisomal, or apoplastic), a different physiological, biochemical, and
      molecular response is provoked. We used transcriptome data generated from ROS
      related microarray experiments to assess the specificity of ROS-driven transcript
      expression. Data sets obtained by exogenous application of oxidative stress
      causing agents (methyl viologen, Alternaria alternata toxin, 3-aminotriazole, and
      ozone) and from a mutant (fluorescent) and transgenic plants, in which the
      activity of an individual antioxidant enzyme was perturbed (catalase, cytosolic
      ascorbate peroxidase, and copper/zinc superoxide dismutase), were compared. In
      total, the abundance of nearly 26,000 transcripts of Arabidopsis (Arabidopsis
      thaliana) was monitored in response to different ROS. Overall, 8,056, 5,312, and
      3,925 transcripts showed at least a 3-, 4-, or 5-fold change in expression,
      respectively. In addition to marker transcripts that were specifically regulated
      by hydrogen peroxide, superoxide, or singlet oxygen, several transcripts were
      identified as general oxidative stress response markers because their steady
      state levels were at least 5-fold elevated in most experiments. We also assessed
      the expression characteristics of all annotated transcription factors and
      inferred new candidate regulatory transcripts that could be responsible for
      orchestrating the specific transcriptomic signatures triggered by different ROS.
      Our analysis provides a framework that will assist future efforts to address the
      impact of ROS signals within environmental stress conditions and elucidate the
      molecular mechanisms of the oxidative stress response in plants.

PMID- 16603661
TI  - Transcription analysis of arabidopsis membrane transporters and hormone pathways
      during developmental and induced leaf senescence.
AB  - A comparative transcriptome analysis for successive stages of Arabidopsis
      (Arabidopsis thaliana) developmental leaf senescence (NS), darkening-induced
      senescence of individual leaves attached to the plant (DIS), and senescence in
      dark-incubated detached leaves (DET) revealed many novel senescence-associated
      genes with distinct expression profiles. The three senescence processes share a
      high number of regulated genes, although the overall number of regulated genes
      during DIS and DET is about 2 times lower than during NS. Consequently, the
      number of NS-specific genes is much higher than the number of DIS- or DET
      specific genes. The expression profiles of transporters (TPs), receptor-like
      kinases, autophagy genes, and hormone pathways were analyzed in detail. The
      Arabidopsis TPs and other integral membrane proteins were systematically
      reclassified based on the Transporter Classification system. Coordinate
      activation or inactivation of several genes is observed in some TP families in
      all three or only in individual senescence types, indicating differences in the
      genetic programs for remobilization of catabolites. Characteristic senescence
      type-specific differences were also apparent in the expression profiles of
      (putative) signaling kinases. For eight hormones, the expression of biosynthesis,
      metabolism, signaling, and (partially) response genes was investigated. In most
      pathways, novel senescence-associated genes were identified. The expression
      profiles of hormone homeostasis and signaling genes reveal additional players in
      the senescence regulatory network.

PMID- 16603663
TI  - Ascorbate oxidase-dependent changes in the redox state of the apoplast modulate
      gene transcript accumulation leading to modified hormone signaling and
      orchestration of defense processes in tobacco.
AB  - The role of the redox state of the apoplast in hormone responses, signaling
      cascades, and gene expression was studied in transgenic tobacco (Nicotiana
      tabacum) plants with modified cell wall-localized ascorbate oxidase (AO). High AO
      activity specifically decreased the ascorbic acid (AA) content of the apoplast
      and altered plant growth responses triggered by hormones. Auxin stimulated shoot
      growth only when the apoplastic AA pool was reduced in wild-type or AO antisense
      lines. Oxidation of apoplastic AA in AO sense lines was associated with loss of
      the auxin response, higher mitogen-activated protein kinase activities, and
      susceptibility to a virulent strain of the pathogen Pseudomonas syringae. The
      total leaf glutathione pool, the ratio of reduced glutathione to glutathione
      disulfide, and glutathione reductase activities were similar in the leaves of all
      lines. However, AO sense leaves exhibited significantly lower dehydroascorbate
      reductase and ascorbate peroxidase activities than wild-type and antisense
      leaves. The abundance of mRNAs encoding antioxidant enzymes was similar in all
      lines. However, the day/night rhythms in the abundance of transcripts encoding
      the three catalase isoforms were changed in response to the AA content of the
      apoplast. Other transcripts influenced by AO included photorespiratory genes and
      a plasma membrane Ca(2+) channel-associated gene. We conclude that the redox
      state of the apoplast modulates plant growth and defense responses by regulating
      signal transduction cascades and gene expression patterns. Hence, AO activity,
      which modulates the redox state of the apoplastic AA pool, strongly influences
      the responses of plant cells to external and internal stimuli.

PMID- 16603665
TI  - Response of the leaf cell wall to desiccation in the resurrection plant
      Myrothamnus flabellifolius.
AB  - The Myrothamnus flabellifolius leaf cell wall and its response to desiccation
      were investigated using electron microscopic, biochemical, and immunocytochemical
      techniques. Electron microscopy revealed desiccation-induced cell wall folding in
      the majority of mesophyll and epidermal cells. Thick-walled vascular tissue and
      sclerenchymous ribs did not fold and supported the surrounding tissue, thereby
      limiting the extent of leaf shrinkage and allowing leaf morphology to be rapidly
      regained upon rehydration. Isolated cell walls from hydrated and desiccated M.
      flabellifolius leaves were fractionated into their constituent polymers and the
      resulting fractions were analyzed for monosaccharide content. Significant
      differences between hydrated and desiccated states were observed in the water
      soluble buffer extract, pectin fractions, and the arabinogalactan protein-rich
      extract. A marked increase in galacturonic acid was found in the alkali-insoluble
      pectic fraction. Xyloglucan structure was analyzed and shown to be of the
      standard dicotyledonous pattern. Immunocytochemical analysis determined the
      cellular location of the various epitopes associated with cell wall components,
      including pectin, xyloglucan, and arabinogalactan proteins, in hydrated and
      desiccated leaf tissue. The most striking observation was a constitutively
      present high concentration of arabinose, which was associated with pectin,
      presumably in the form of arabinan polymers. We propose that the arabinan-rich
      leaf cell wall of M. flabellifolius possesses the necessary structural properties
      to be able to undergo repeated periods of desiccation and rehydration.

PMID- 16603664
TI  - Nitric oxide- and hydrogen peroxide-responsive gene regulation during cell death
      induction in tobacco.
AB  - Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) are regulatory molecules in
      various developmental processes and stress responses. Tobacco (Nicotiana tabacum)
      leaves exposed to moderate high light dramatically potentiated NO-mediated cell
      death in catalase-deficient (CAT1AS) but not in wild-type plants, providing
      genetic evidence for a partnership between NO and H(2)O(2) during the induction
      of programmed cell death. With this experimental model system, the specific
      impact on gene expression was characterized by either NO or H(2)O(2) alone or
      both molecules combined. By means of genome-wide cDNA-amplified fragment length
      polymorphism analysis, transcriptional changes were compared in high light
      treated CAT1AS and wild-type leaves treated with or without the NO donor sodium
      nitroprusside. Differential gene expression was detected for 214 of the
      approximately 8,000 transcript fragments examined. For 108 fragments, sequence
      analysis revealed homology to genes with a role in signal transduction, defense
      response, hormone interplay, proteolysis, transport, and metabolism.
      Surprisingly, only 16 genes were specifically induced by the combined action of
      NO and H(2)O(2), whereas the majority were regulated by either of them alone. At
      least seven transcription factors were mutually up-regulated, indicating
      significant overlap between NO and H(2)O(2) signaling pathways. These results
      consolidate significant cross-talk between NO and H(2)O(2), provide new insight
      into the early transcriptional response of plants to increased NO and H(2)O(2)
      levels, and identify target genes of the combined action of NO and H(2)O(2)
      during the induction of plant cell death.

PMID- 16603666
TI  - Arabidopsis INOSITOL TRANSPORTER4 mediates high-affinity H+ symport of
      myoinositol across the plasma membrane.
AB  - Four genes of the Arabidopsis (Arabidopsis thaliana) monosaccharide transporter
      like superfamily share significant homology with transporter genes previously
      identified in the common ice plant (Mesembryanthemum crystallinum), a model
      system for studies on salt tolerance of higher plants. These ice plant
      transporters had been discussed as tonoplast proteins catalyzing the inositol
      dependent efflux of Na(+) ions from vacuoles. The subcellular localization and
      the physiological role of the homologous proteins in the glycophyte Arabidopsis
      were unclear. Here we describe Arabidopsis INOSITOL TRANSPORTER4 (AtINT4), the
      first member of this subgroup of Arabidopsis monosaccharide transporter-like
      transporters. Functional analyses of the protein in yeast (Saccharomyces
      cerevisiae) and Xenopus laevis oocytes characterize this protein as a highly
      specific H(+) symporter for myoinositol. These activities and analyses of the
      subcellular localization of an AtINT4 fusion protein in Arabidopsis and tobacco
      (Nicotiana tabacum) reveal that AtINT4 is located in the plasma membrane. AtINT4
      promoter-reporter gene plants demonstrate that AtINT4 is strongly expressed in
      Arabidopsis pollen and phloem companion cells. The potential physiological role
      of AtINT4 is discussed.

PMID- 16603667
TI  - The significance of C16 fatty acids in the sn-2 positions of glycerolipids in the
      photosynthetic growth of Synechocystis sp. PCC6803.
AB  - Most extant cyanobacteria contain C16 fatty acids in the sn-2 positions of
      glycerolipids, which are regulated by lysophosphatidic acid acyltransferase
      (LPAAT; EC 2.3.1.51). Synechocystis sp. PCC6803 contains sll1848, sll1752, and
      slr2060 as putative acyltransferase genes. sll1848 was recently reported to
      encode an indispensable palmitoyl-specific LPAAT; however, here we show that each
      of the three genes is dispensable. Delta1848 and Delta1848 Delta2060 cells had
      markedly higher contents of stearate (18:0), oleate (18:1), and linoleate (18:2)
      in place of palmitate (16:0) in the sn-2 positions, suggesting that Delta1848
      Delta2060 cells incorporate 18:0 and 18:1 in the sn-2 positions. The levels of
      sll1752 transcripts increased in Delta1848 Delta2060 cells. This was accompanied
      by increased LPAAT activity toward 18:0 coenzyme A and its derivative in the
      membrane fraction. From these findings, together with the activity of a
      recombinant sll1752 protein and complementation of the Escherichia coli LPAAT
      mutant plsC, we conclude that sll1752 encodes a second LPAAT that prefers
      stearoyl and oleoyl substrates. Delta1848 Delta2060 cells grew slowly at 30
      degrees C at lower cell density, and exhibited more severe damage at 20 degrees C
      than wild-type cells. Furthermore, Delta1848 Delta2060 cells exhibited
      photoinhibition more severely than wild-type cells. A phycobilisome core-membrane
      linker protein (slr0335) was also found to be susceptible to protein extraction
      under our conditions; its content decreased in the membrane fractions of
      Delta1848 Delta2060 cells. We conclude that C16 fatty acids in sn-2 positions are
      preferred in the photosynthetic growth of this cyanobacterium, despite sll1752
      orthologs being conserved in most cyanobacteria. However, no sll1752 ortholog is
      conserved among photosynthetic eukaryotes including Cyanidioschyzon merolae.

PMID- 16603668
TI  - Promoter shuffling at a nuclear gene for mitochondrial RPL27. Involvement of
      interchromosome and subsequent intrachromosome recombinations.
AB  - The Reclinomonas americana mitochondrial genome contains a mitochondrial
      ribosomal protein L27 (rpl27) gene, whereas the rpl27 gene is absent from all
      plant mitochondrial genomes examined to date. This suggests that plant
      mitochondrial rpl27 genes have been transferred previously from the mitochondrial
      genome to the nuclear genome. A nuclear cDNA encoding mitochondrial RPL27 was
      identified in rice (Oryza sativa). Three similar sequences were identified: rpl27
      1 and rpl27-2 on chromosome 8 and rpl27-3 on chromosome 4. Harr plot analysis
      suggests that they were generated by inter- and intrachromosomal duplications.
      Interestingly, the transcribed rpl27 gene (rpl27-1) acquired a promoter sequence
      that was derived from the rice spt16 (Osspt16) gene, the homolog of a global
      transcription factor in yeast (Saccharomyces cerevisiae) located downstream from
      the rpl27-3 sequence on chromosome 4, after inter- and intrachromosomal
      recombination. Reverse transcription-PCR and promoter assay revealed that the
      rpl27 mRNAs were mainly transcribed from rpl27-1. A repeat of seven nucleotides
      (AATAGTT) was identified at the junction of rpl27-1 and rpl27-2 on chromosome 8,
      and the same repeat was also identified at the 5' end of rpl27-2 and the 3' end
      of rpl27-1. This repeat (AATAGTT) contains the hot-spot sequence AGTT, which is
      preferentially recognized by topoisomerase I in wheat (Triticum aestivum) germ,
      suggesting the involvement of topoisomerase I in this recombination. We here
      report the example of promoter shuffling and show that this promoter shuffling
      resulted from a recent segmental duplication through inter- and intrachromosomal
      recombination events.

PMID- 16603669
TI  - Transcriptome analysis of cold acclimation in barley albina and xantha mutants.
AB  - Previously, we have shown that barley (Hordeum vulgare) plants carrying a
      mutation preventing chloroplast development are completely frost susceptible as
      well as impaired in the expression of several cold-regulated genes. Here we
      investigated the transcriptome of barley albina and xantha mutants and the
      corresponding wild type to assess the effect of the chloroplast on expression of
      cold-regulated genes. First, by comparing control wild type against cold-hardened
      wild-type plants 2,735 probe sets with statistically significant changes (P =
      0.05; > or = 2-fold change) were identified. Expression of these wild-type cold
      regulated genes was then analyzed in control and cold-hardened mutants. Only
      about 11% of the genes cold regulated in wild type were regulated to a similar
      extent in all genotypes (chloroplast-independent cold-regulated genes); this
      class includes many genes known to be under C-repeat binding factor control. C
      repeat binding factor genes were also equally induced in mutants and wild-type
      plants. About 67% of wild-type cold-regulated genes were not regulated by cold in
      any mutant (chloroplast-dependent cold-regulated genes). We found that the lack
      of cold regulation in the mutants is due to the presence of signaling pathway(s)
      normally cold activated in wild type but constitutively active in the mutants, as
      well as to the disruption of low-temperature signaling pathway(s) due to the
      absence of active chloroplasts. We also found that photooxidative stress
      signaling pathway is constitutively active in the mutants. These results
      demonstrate the major role of the chloroplast in the control of the molecular
      adaptation to cold.

PMID- 16603670
TI  - Bioactive properties of iron-containing carbon monoxide-releasing molecules.
AB  - Carbon monoxide-releasing molecules (CO-RMs) are compounds capable of delivering
      controlled amounts of CO within a cellular environment. Ruthenium-based carbonyls
      [tricarbonyldichloro ruthenium(II) dimer and tricarbonylchloro
      (glycinato)ruthenium(II)] and boronacorbonates (sodium boranocarbonate) have been
      shown to promote vasodilatory, cardioprotective, and anti-inflammatory activities
      in a variety of experimental models. Here, we extend our previous studies by
      showing that eta-4-(4-bromo-6-methyl-2-pyrone)tricarbonyl iron (0) (CORM-F3), an
      irontricarbonyl complex that contains a 2-pyrone motif, liberates CO in vitro and
      exerts pharmacological actions that are typical of CO gas. Specifically, CORM-F3
      caused vasorelaxation in isolated aortic rings and inhibited the inflammatory
      response (e.g., nitrite production) of RAW264.7 macrophages stimulated with
      endotoxin in a dose-dependent fashion. By analyzing the rate of CO release, we
      found that when the bromide at the 4-position of the 2-pyrone CORM-F3 is
      substituted with a chloride group [eta-4-(4-chloro-6-methyl-2-pyrone)tricarbonyl
      iron (0) (CORM-F8)], the rate of CO release is significantly decreased (4.5
      fold), and a further decrease is observed when the 4- and 6-positions are
      substituted with a methyl group [eta-4-(4-methyl-6-methyl-2-pyrone)tricarbonyl
      iron (0) (CORM-F11)] or a hydrogen [eta-4-(4-chloro-2-pyrone)tricarbonyl iron (0)
      (CORM-F7)], respectively. Interestingly, the compounds containing halogens at the
      4-position and the methyl at the 6-position of the 2-pyrone ring (CORM-F3 and
      CORM-F8) were found to be less cytotoxic compared with other CO-RMs when tested
      in RAW246.7 macrophages. Thus, iron-based carbonyls mediate pharmacological
      responses that are achieved through liberation of CO and the nature of the
      substituents in the organic ligand have a profound effect on both the rate of CO
      release and cytotoxicity.

PMID- 16603671
TI  - Role of phosphorus and vitamin D analogs in the pathogenesis of vascular
      calcification.
AB  - Vascular calcification is a mortality risk factor for stage 5 chronic kidney
      disease patients. We investigated the role of phosphorus and vitamin D analogs in
      the pathogenesis of vascular calcification using in vivo, ex vivo, and in vitro
      models. Our results demonstrate that uremic rats receiving a hyperphosphatemia
      inducing diet did not exhibit aortic calcification despite elevated levels of
      serum phosphorus and calcium-phosphorus (CaxP) product. The vitamin D analog
      1alpha-hydroxyvitamin-D2 [1alpha(OH)D2] at 0.17 microg/kg raised serum calcium,
      phosphorus, CaxP product, and aortic calcification in the uremic rats, but 19-nor
      1alpha,25(OH)2D2 (19-nor) at the same dose had no significant effect. At 0.67
      microg/kg, both 1alpha(OH)D2 and 19-nor had similar effects on serum calcium,
      phosphorus, and CaxP product, but only 1alpha(OH)D2 induced significant aortic
      calcification. Only aortic rings from 1alpha(OH)D2-treated uremic rats exhibited
      a significant increase in 45Ca uptake ex vivo. When aortic rings from normal rats
      or a primary culture of human coronary artery smooth muscle cells were treated
      with phosphorus or vitamin D analogs in vitro, high phosphorus induced calcium
      accumulation and/or 45Ca uptake in a dose- or time-dependent manner, whereas
      vitamin D analogs including 1alpha(OH)D2 up to 100 nM had no significant effect
      despite the presence of a functional vitamin D receptor. However, serum from
      1alpha(OH)D2-treated uremic rats induced 45Ca uptake into smooth muscle cells
      cultured in high phosphorus. These results suggest that the regulation of
      vascular calcification in vivo cannot be easily replicated in the ex vivo or in
      vitro models, and high phosphorus and some vitamin D analogs such as 1alpha(OH)D2
      exert interactive effects on modulating vascular calcification.

PMID- 16603672
TI  - Preventive and therapeutic potential of p38 alpha-selective mitogen-activated
      protein kinase inhibitor in nonobese diabetic mice with type 1 diabetes.
AB  - Mitogen-activated protein kinases (MAPKs) and heat shock proteins (HSPs) are
      ubiquitous proteins that function within T cells in both normal and stress
      related pathophysiological states, including type 1 diabetes. The nonobese
      diabetic (NOD) mouse spontaneously develops T cell-mediated autoimmune pancreatic
      beta cell destruction that is similar to type 1 diabetes in humans. Because p38
      MAPKs have been shown to modulate T cell function, we studied the effects of a
      p38alpha MAPK-selective inhibitor, indole-5-carboxamide (SD-169), on the
      development and progression of type 1 diabetes in the NOD mouse. In preventive
      treatment studies, SD-169 significantly reduced p38 and HSP60 expression in T
      cells of the pancreatic beta islets. Following treatment, the incidence of
      diabetes as determined by blood glucose levels was significantly lower, and
      immuno-histochemistry of pancreatic beta islet tissue demonstrated significant
      reduction in CD5+ T cell infiltration in the SD-169 treatment group as compared
      with untreated NOD mice. In therapeutic studies using mildly and moderately
      hyperglycemic NOD mice, SD-169 treatment lowered blood glucose and improved
      glucose homeostasis. Furthermore, following cessation of SD-169 treatment, NOD
      mice showed significant arrest of diabetes. In conclusion, we report that this
      p38alpha-selective inhibitor prevents the development and progression of diabetes
      in NOD mice by inhibiting T cell infiltration and activation, thereby preserving
      beta cell mass via inhibition of the p38 MAPK signaling pathway. These results
      have bearing on current prophylactic and therapeutic protocols using p38alpha
      selective inhibitors in the prediabetic period for children at high risk of type
      1 diabetes, in the honeymoon period, and for adults with latent autoimmune
      diabetes.

PMID- 16603673
TI  - Transcriptional feedback oscillators: maybe, maybe not...
AB  - The molecular mechanism of circadian rhythmicity is usually modeled by a
      transcription/translation feedback oscillator in which clock proteins negatively
      feed back on their own transcription to produce rhythmic levels of clock protein
      mRNAs, which in turn cause the production of rhythmic levels of clock proteins.
      This mechanism has been applied to all model organisms for which molecular data
      are available. This review summarizes the increasing number of anomalous
      observations that do not fit the standard molecular mechanism for the model
      organisms Acetabularia, Synechococcus, Drosophila, Neurospora, and mouse. The
      anomalies fall into 2 classes: observations of rhythmicity in the organism when
      transcription of clock genes is held constant, and rhythmicity in the organism
      when clock gene function is missing in knockout mutants. It is concluded that the
      weight of anomalies is now so large that the standard transcription/translation
      mechanism is no longer an adequate model for circadian oscillators. Rhythmic
      transcription may have other functions in the circadian system, such as
      participating in input and output pathways and providing robustness to the
      oscillations. It may be most useful to think in terms of a circadian system that
      uses a noncircadian oscillator consisting of metabolic feedback loops, which
      acquires its circadian properties from additional regulatory molecules such as
      the products of canonical clock genes.

PMID- 16603674
TI  - Drosophila CLOCK is constitutively expressed in circadian oscillator and non
      oscillator cells.
AB  - CLOCK (CLK) is a core component of the transcriptional feedback loops that
      comprise the circadian timekeeping mechanism in Drosophila. As a heterodimer with
      CYCLE (CYC), CLK binds E-boxes to activate the transcription of rhythmically
      expressed genes within and downstream of the circadian clock, but this activation
      unexpectedly occurs at times when CLK is at its lowest levels on Western blots.
      Recent studies demonstrate that CLK also regulates nonrhythmic gene expression
      and behaviors. Despite the critical roles CLK plays within and outside the
      circadian clock, its spatial expression pattern has not been characterized. Using
      a newly developed CLK antibody, the authors show that CLK is coexpressed with
      PERIOD (PER) in canonical oscillator cells throughout the head and body. In
      contrast to PER, however, the levels of CLK immunoreactivity do not cycle in
      intensity, CLK is detected primarily in the nucleus throughout the circadian
      cycle, and CLK is expressed in non-oscillator cells within the lateral and dorsal
      brain, including Kenyon cells, which mediate various forms of learning and
      memory. These results indicate that constitutive levels of nuclear CLK regulate
      rhythmic transcription in circadian oscillator cells and suggest that CLK
      contributes to other behavioral processes by regulating gene expression in non
      oscillator cells.

PMID- 16603675
TI  - PDF cycling in the dorsal protocerebrum of the Drosophila brain is not necessary
      for circadian clock function.
AB  - In Drosophila, the neuropeptide pigment-dispersing factor (PDF) is a likely
      circadian molecule, secreted by central pacemaker neurons (LNvs). PDF is
      expressed in both small and large LNvs (sLNvs and lLNvs), and there are striking
      circadian oscillations of PDF staining intensity in the small cell termini, which
      require a functional molecular clock. This cycling may be relevant to the
      proposed role of PDF as a synchronizer of the clock system or as an output signal
      connecting pacemaker cells to locomotor activity centers. In this study, the
      authors use a generic neuropeptide fusion protein (atrial natriuretic factor
      green fluorescent protein [ANF-GFP]) and show that it can be expressed in the
      same neurons as PDF itself. Yet, ANF-GFP as well as PDF itself does not manifest
      any cyclical accumulation in sLNv termini in adult transgenic flies.
      Surprisingly, the absence of detectable PDF cycling is not accompanied by any
      detectable behavioral pheno-type, since these transgenic flies have normal
      morning and evening anticipation in a light-dark cycle (LD) and are fully
      rhythmic in constant darkness (DD). The molecular clock is also not compromised.
      The results suggest that robust PDF cycling in sLNv termini plays no more than a
      minor role in the Drosophila circadian system and is apparently not even
      necessary for clock output function.

PMID- 16603677
TI  - Evolutionary divergence of circadian and photoperiodic phenotypes in the pitcher
      plant mosquito, Wyeomyia smithii.
AB  - For decades, chronobiologists have investigated the relationship between the
      circadian clock that mediates daily activities and the photoperiodic timer that
      mediates seasonal activities. The main experiment used to infer a circadian basis
      for photoperiodic time measurement is the Nanda-Hamner protocol (NH). Herein, the
      authors compare additive and nonadditive (dominance and epistasis) genetic
      effects that lead to the divergence of populations of the pitcher-plant mosquito,
      Wyeomyia smithii, for critical photoperiod (CPP) and amplitude of the rhythmic
      response to NH for 3 temporal-geographic scales: 1) Over geological time between
      populations in northern and southern clades, 2) over millennial time between
      populations within the northern clade, and 3) over generational time between
      lines selected for long and short CPP from within a single population. The
      authors show that the pattern of additive, dominance, and epistatic effects
      depends on the time scale over which populations or lines have diverged. Patterns
      for genetic differences between populations for CPP and response to NH reveal
      similarities over geological and millennial time scales but differences over
      shorter periods of evolution. These results, and the observation that neither the
      period nor amplitude of the NH rhythm are significantly correlated with CPP among
      populations, lead the authors to conclude that the rhythmic response to NH has
      evolved independently of photoperiodic response in populations of W. smithii. The
      implication is that in this species, genetic modification of the circadian clock
      has not been the basis for the adaptive modification of photoperiodic time
      measurement over the climatic gradient of North America.

PMID- 16603676
TI  - Immunoreactivities to three circadian clock proteins in two ground crickets
      suggest interspecific diversity of the circadian clock structure.
AB  - The closely related crickets Dianemobius nigrofasciatus and Allonemobius allardi
      exhibit similar circadian rhythms and photoperiodic responses, suggesting that
      they possess similar circadian and seasonal clocks. To verify this assumption,
      antisera to Period (PER), Doubletime (DBT), and Cryptochrome (CRY) were used to
      visualize circadian clock neurons in the cephalic ganglia. Immunoreactivities
      referred to as PER-ir, DBT-ir, and CRY-ir were distributed mainly in the optic
      lobes (OL), pars intercerebralis (PI), dorsolateral protocerebrum, and the
      subesophageal ganglion (SOG). A system of immunoreactive cells in the OL
      dominates in D. nigrofasciatus, while immunoreactivities in the PI and SOG
      prevail in A. allardi. Each OL of D. nigrofasciatus contains 3 groups of cells
      that coexpress PER-ir and DBT-ir and send processes over the frontal medulla face
      to the inner lamina surface, suggesting functional linkage to the compound eye.
      Only 2 pairs of PER-ir cells (no DBT-ir) were found in the OL of A. allardi.
      Several groups of PER-ir cells occur in the brain of both species. The PI also
      contains DBT-ir and CRY-ir cells, but in A. allardi, most of the DBT-ir is
      confined to the SOG. Most immunoreactive cells in the PI and in the dorsolateral
      brain send their fibers to the contralateral corpora cardiaca and corpora allata.
      The proximity and, in some cases, proven identity of the PER-ir, DBT-ir, and CRY
      ir perikarya are consistent with presumed interactions between the examined clock
      components. The antigens were always found in the cytoplasm, and no diurnal
      oscillations in their amounts were detected. The photoperiod, which controls
      embryonic diapause, the rate of larval development, and the wing length of
      crickets, had no discernible effect on either distribution or the intensity of
      the immunostaining.

PMID- 16603678
TI  - Expression of clock and clock-driven genes in the rat suprachiasmatic nucleus
      during late fetal and early postnatal development.
AB  - The SCN as a site of the circadian clock itself exhibits rhythmicity. A molecular
      clockwork responsible for the rhythmicity consists of clock genes and their
      negative and positive transcriptional-translational feedback loops. The authors'
      previous work showed that rhythms in clock gene expression in the rat SCN were
      not yet detectable at embryonic day (E) 19 but were already present at postnatal
      day (P) 3. The aim of the present study was to elucidate when during the interval
      E19-P3 the rhythms start to develop in clock gene expression and in clock
      controlled, namely in arginine-vasopressin (AVP), gene expression. Daily profiles
      of Per1, Per2, Cry1, Bmal1, and Clock mRNA and of AVP heteronuclear (hn) RNA as
      an indicator of AVP gene transcription were assessed in the SCN of fetuses at E20
      and of newborn rats at P1 and P2 by the in situ hybridization method. At E20,
      formation of a rhythm in Per1 expression was indicated, but no rhythms in
      expression of other clock genes or of the AVP gene were detected. At P1, rhythms
      in Per1, Bmal1, and AVP and a forming rhythm in Per2 but no rhythm in Cry1
      expression were present in the SCN. The Per1 mRNA rhythm was, however, only
      slightly pronounced. The Bmal1 mRNA rhythm, although pronounced, exhibited still
      an atypical shape. Only the AVP hnRNA rhythm resembled that of adult rats. At P2,
      marked rhythms of Per1, Per2, and Bmal1 and a forming rhythm of Cry1, but not of
      Clock, expression were present. The data suggest that rhythms in clock gene
      expression for the most part develop postnatally and that other mechanisms
      besides the core clockwork might be involved in the generation of the rhythmic
      AVP gene expression in the rat SCN during early ontogenesis.

PMID- 16603679
TI  - Circadian rhythms in murine pups develop in absence of a functional maternal
      circadian clock.
AB  - A genetic approach was used to investigate whether the emergence of circadian
      rhythms in murine pups is dependent on a functional maternal clock. Arrhythmic
      females bearing either the mPer1Brdm1/Per2Brdm1 or mPer2Brdm1/Cry1-/- double
      mutant genotype were crossed with wild-type males under constant darkness. The
      heterozygous offspring have the genetic constitution for a functional circadian
      clock. Individual pups born to arrhythmic mPer1Brdm1/Per2Brdm1 and
      mPer2Brdm1/Cry1-/- mothers in constant darkness without external zeitgeber
      developed normal circadian rhythms, but their clocks were less synchronized to
      each other compared to wild-type animals. These findings indicate that
      development of circadian rhythms does not depend on a functional circadian clock
      in maternal tissue, extending previous findings obtained from pups born to SCN
      lesioned mothers.

PMID- 16603682
TI  - Regularized linear discriminant analysis and its application in microarrays.
AB  - In this paper, we introduce a modified version of linear discriminant analysis,
      called the "shrunken centroids regularized discriminant analysis" (SCRDA). This
      method generalizes the idea of the "nearest shrunken centroids" (NSC) (Tibshirani
      and others, 2003) into the classical discriminant analysis. The SCRDA method is
      specially designed for classification problems in high dimension low sample size
      situations, for example, microarray data. Through both simulated data and real
      life data, it is shown that this method performs very well in multivariate
      classification problems, often outperforms the PAM method (using the NSC
      algorithm) and can be as competitive as the support vector machines classifiers.
      It is also suitable for feature elimination purpose and can be used as gene
      selection method. The open source R package for this method (named "rda") is
      available on CRAN (http://www.r-project.org) for download and testing.

PMID- 16603683
TI  - Regulation of myocardial substrate metabolism during increased energy
      expenditure: insights from computational studies.
AB  - In response to exercise, the heart increases its metabolic rate severalfold while
      maintaining energy species (e.g., ATP, ADP, and Pi) concentrations constant;
      however, the mechanisms that regulate this response are unclear. Limited
      experimental studies show that the classic regulatory species NADH and NAD+ are
      also maintained nearly constant with increased cardiac power generation, but
      current measurements lump the cytosol and mitochondria and do not provide dynamic
      information during the early phase of the transition from low to high work
      states. In the present study, we modified our previously published computational
      model of cardiac metabolism by incorporating parallel activation of ATP
      hydrolysis, glycolysis, mitochondrial dehydrogenases, the electron transport
      chain, and oxidative phosphorylation, and simulated the metabolic responses of
      the heart to an abrupt increase in energy expenditure. Model simulations showed
      that myocardial oxygen consumption, pyruvate oxidation, fatty acids oxidation,
      and ATP generation were all increased with increased energy expenditure, whereas
      ATP and ADP remained constant. Both cytosolic and mitochondrial NADH/NAD+
      increased during the first minutes (by 40% and 20%, respectively) and returned to
      the resting values by 10-15 min. Furthermore, model simulations showed that an
      altered substrate selection, induced by either elevated arterial lactate or
      diabetic conditions, affected cytosolic NADH/NAD+ but had minimal effects on the
      mitochondrial NADH/NAD+, myocardial oxygen consumption, or ATP production. In
      conclusion, these results support the concept of parallel activation of metabolic
      processes generating reducing equivalents during an abrupt increase in cardiac
      energy expenditure and suggest there is a transient increase in the mitochondrial
      NADH/NAD+ ratio that is independent of substrate supply.

PMID- 16603684
TI  - Relationship of pulmonary vein flow to left ventricular short-axis epicardial
      displacement in diastole: model-based prediction with in vivo validation.
AB  - Previous studies in healthy humans have established that the (approximately 850
      ml) volume enclosed by the pericardial sac is nearly constant over the cardiac
      cycle, exhibiting a transient approximately 5% decrease (approximately 40 ml)
      from end diastole to end systole. This volume decrease manifests as a "crescent"
      at the ventricular free wall level when short-axis MRI images of the epicardial
      surface acquired at end systole and end diastole are superimposed. On the basis
      of the (near) constant-volume property of the four-chambered heart, the volume
      decrease ("crescent effect") must be restored during subsequent early diastolic
      filling via the left atrial conduit volume. Therefore, volume conservation-based
      modeling predicts that pulmonary venous (PV) Doppler D-wave volume must be
      causally related to the radial displacement of the epicardium (Delta) (i.e.,
      magnitude of "crescent effect" in the radial direction). We measured Delta from M
      mode echocardiographic images and measured D-wave velocity-time integral (VTI)
      from Doppler PV flow of the right superior PV in 11 subjects with catheterization
      determined normal physiology. In accordance with model prediction, high
      correlation was observed between Delta and D-wave VTI (r=0.86) and early D-wave
      VTI measured to peak D-wave velocity (r=0.84). Furthermore, selected subjects
      with various pathological conditions had values of Delta that differed
      significantly. These observations demonstrate the volume conservation-based
      causal relationship between radial pericardial displacement of the left ventricle
      and the PV D-wave-generated filling volume in healthy subjects as well as the
      potential role of the M-mode echo-derived radial epicardial displacement index
      Delta as a regional (radial) parameter of diastolic function.

PMID- 16603685
TI  - Functional alterations after cardiac sodium-calcium exchanger overexpression in
      heart failure.
AB  - The sodium-calcium exchanger (NCX) is discussed as one of the key proteins
      involved in heart failure. However, the causal role and the extent to which NCX
      contributes to contractile dysfunction during heart failure are poorly
      understood. NCX overexpression was induced by infection with an adenovirus coding
      for NCX, which coexpressed green fluorescence protein (GFP) (AdNCX) by ex vivo
      gene transfer to nonfailing and failing rabbit cardiomyocytes. Myocardial gene
      transfer in rabbits in vivo was achieved by adenoviral delivery via aortic cross
      clamping. Peak cell shortening of cardiomyocytes was determined photo-optically.
      Hemodynamic parameters in vivo were determined by echocardiography (fractional
      shortening) and tip catheter [maximal first derivative of left ventricular (LV)
      pressure (dP/dt(max)); maximal negative derivative of LV pressure (-dP/dt(max))].
      Peak cell shortening was depressed after NCX gene delivery in isolated nonfailing
      and in failing cardiomyocytes. In nonfailing rabbits in vivo, basal systolic
      contractility (fractional shortening and dP/dt(max)) and maximum rate of LV
      relaxation (-dP/dt(max)) in vivo were largely unaffected after NCX
      overexpression. However, during heart failure, long-term NCX overexpression over
      2 wk significantly improved fractional shortening and dP/dt(max) compared with
      AdGFP-infected rabbits, both without inotropic stimulation and after beta
      adrenergic stimulation with isoproterenol. -dP/dt(max) was also improved after
      NCX overexpression in the failing rabbits group. These results indicate that
      short-term effects of NCX overexpression impair contractility of isolated failing
      and nonfailing rabbit cardiomyocytes. NCX overexpression over 2 wk in vivo does
      not seem to affect myocardial contractility in nonfailing rabbits. Interestingly,
      in vivo overexpression of NCX decreased the progression of systolic and diastolic
      contractile dysfunction and improved beta-adrenoceptor-mediated contractile
      reserve in heart failure in rabbits in vivo.

PMID- 16603686
TI  - KCa channel insensitivity to Ca2+ sparks underlies fractional uncoupling in
      newborn cerebral artery smooth muscle cells.
AB  - In smooth muscle cells, localized intracellular Ca2+ transients, termed "Ca2+
      sparks," activate several large-conductance Ca2+-activated K+ (KCa) channels,
      resulting in a transient KCa current. In some smooth muscle cell types, a
      significant proportion of Ca2+ sparks do not activate KCa channels. The goal of
      this study was to explore mechanisms that underlie fractional Ca2+ spark-KCa
      channel coupling. We investigated whether membrane depolarization or ryanodine
      sensitive Ca2+ release (RyR) channel activation modulates coupling in newborn (1-
      to 3-day-old) porcine cerebral artery myocytes. At steady membrane potentials of 
      40, 0, and +40 mV, mean transient KCa current frequency was approximately 0.18,
      0.43, and 0.26 Hz and KCa channel activity [number of KCa channels activated by
      Ca2+ sparksxopen probability of KCa channels at peak of Ca2+ sparks (NPo)] at the
      transient KCa current peak was approximately 4, 12, and 24, respectively.
      Depolarization between -40 and +40 mV increased KCa channel sensitivity to Ca2+
      sparks and elevated the percentage of Ca2+ sparks that activated a transient KCa
      current from 59 to 86%. In a Ca2+-free bath solution or in diltiazem, a voltage
      dependent Ca2+ channel blocker, steady membrane depolarization between -40 and
      +40 mV increased transient KCa current frequency up to approximately 1.6-fold. In
      contrast, caffeine (10 microM), an RyR channel activator, increased mean
      transient KCa current frequency but did not alter Ca2+ spark-KCa channel
      coupling. These data indicate that coupling is increased by mechanisms that
      elevate KCa channel sensitivity to Ca2+ sparks, but not by RyR channel
      activation. Overall, KCa channel insensitivity to Ca2+ sparks is a prominent
      factor underlying fractional Ca2+ spark uncoupling in newborn cerebral artery
      myocytes.

PMID- 16603687
TI  - Abdominal aortic hemodynamics in young healthy adults at rest and during lower
      limb exercise: quantification using image-based computer modeling.
AB  - Localization of atherosclerotic lesions in the abdominal aorta has been
      previously correlated to areas of adverse hemodynamic conditions, such as flow
      recirculation, low mean wall shear stress, and high temporal oscillations in
      shear. Along with its many systemic benefits, exercise is also proposed to have
      local benefits in the vasculature via the alteration of these regional flow
      patterns. In this work, subject-specific models of the human abdominal aorta were
      constructed from magnetic resonance angiograms of five young, healthy subjects,
      and computer simulations were performed under resting and exercise (50% increase
      in resting heart rate) pulsatile flow conditions. Velocity fields and spatial
      variations in mean wall shear stress (WSS) and oscillatory shear index (OSI) are
      presented. When averaged over all subjects, WSS increased from 4.8 +/- 0.6 to
      31.6 +/- 5.7 dyn/cm2 and OSI decreased from 0.22 +/- 0.03 to 0.03 +/- 0.02 in the
      infrarenal aorta between rest and exercise. WSS significantly increased, whereas
      OSI decreased between rest and exercise at the supraceliac, infrarenal, and
      suprabifurcation levels, and significant differences in WSS were found between
      anterior and posterior sections. These results support the hypothesis that
      exercise provides localized benefits to the cardiovascular system through acute
      mechanical stimuli that trigger longer-term biological processes leading to
      protection against the development or progression of atherosclerosis.

PMID- 16603688
TI  - JNK activation decreases PP2A regulatory subunit B56alpha expression and mRNA
      stability and increases AUF1 expression in cardiomyocytes.
AB  - A central feature of heart disease is a molecular remodeling of signaling
      pathways in cardiac myocytes. This study focused on novel molecular elements of
      MAPK-mediated alterations in the pattern of gene expression of the protein
      phosphatase 2A (PP2A). In an established model of sustained JNK activation, a 70%
      decrease in expression of the targeting subunit of PP2A, B56alpha, was observed
      in either neonatal or adult cardiomyocytes. This loss in protein abundance was
      accompanied by a decrease of 69% in B56alpha mRNA steady-state levels. Given that
      the 3'-untranslated region of this transcript contains adenylate-uridylate-rich
      elements known to regulate mRNA degradation, experiments explored the notion that
      instability of B56alpha mRNA accounts for the response. mRNA time-course analyses
      with real-time PCR methods showed that B56alpha transcript was transformed from a
      stable (no significant decay over 1 h) to a labile form that rapidly degraded
      within minutes. These results were supported by complementary experiments that
      revealed that the RNA-binding protein AUF1, known to destabilize target mRNA, was
      increased fourfold in JNK-activated cells. A variety of other stress-related
      stimuli, such as p38 MAPK activation and phorbol ester, upregulated AUF1
      expression in cultured cardiac cells as well. In addition, gel mobility shift
      assays demonstrated that p37AUF1 binds with nanomolar affinity to segments of the
      B56alpha 3'-untranslated region. Thus these studies provide new evidence that
      signaling-induced mRNA instability is an important mechanism that underlies the
      changes in the pattern of gene expression evoked by stress-activated pathways in
      cardiac cells.

PMID- 16603689
TI  - Caveolin-1 and regulation of cellular cholesterol homeostasis.
AB  - Caveolae are 50- to 100-nm cell surface plasma membrane invaginations present in
      terminally differentiated cells. They are characterized by the presence of
      caveolin-1, sphingolipids, and cholesterol. Caveolin-1 is thought to play an
      important role in the regulation of cellular cholesterol homeostasis, a process
      that needs to be properly controlled to limit and prevent cholesterol
      accumulation and eventually atherosclerosis. We have recently generated caveolin
      1-deficient [Cav-1(-/-)] mice in which caveolae organelles are completely
      eliminated from all cell types, except cardiac and skeletal muscle. In the
      present study, we examined the metabolism of cholesterol in wild-type (WT) and
      Cav-1(-/-) mouse embryonic fibroblasts (MEFs) and mouse peritoneal macrophages
      (MPMs). We observed that Cav-1(-/-) MEFs are enriched in esterified cholesterol
      but depleted of free cholesterol compared with their wild-type counterparts.
      Similarly, Cav-1(-/-) MPMs also contained less free cholesterol and were enriched
      in esterified cholesterol on cholesterol loading. In agreement with this finding,
      caveolin-1 deficiency was associated with reduced free cholesterol synthesis but
      increased acyl-CoA:cholesterol acyl-transferase (ACAT) activity. In wild-type
      MPMs, we observed that caveolin-1 was markedly upregulated on cholesterol
      loading. Despite these differences, cellular cholesterol efflux from MEFs and
      MPMs to HDL was not affected in the Cav-1-deficient cells. Neither ATP-binding
      cassette transporter G1 (ABCG1)- nor scavenger receptor class B type I (SR-BI)
      mediated cholesterol efflux was affected. Cellular cholesterol efflux to
      apolipoprotein A-I was not significantly reduced in Cav-1(-/-) MPMs compared with
      wild-type MPMs. However, ABCA1-mediated cholesterol efflux was clearly more
      sensitive to the inhibitory effects of glyburide in Cav-1(-/-) MPMs versus WT
      MPMs. Taken together, these findings suggest that caveolin-1 plays an important
      role in the regulation of intracellular cholesterol homeostasis and can modulate
      the activity of other proteins that are involved in the regulation of
      intracellular cholesterol homeostasis.

PMID- 16603690
TI  - Effects of dexamethasone and L-canavanine on the intracellular calcium
      contraction relation of the rat tail artery during septic shock.
AB  - The intracellular mechanism by which sepsis lowers vascular reactivity and the
      subsequent reversal by dexamethasone or nitric oxide synthase (NOS) inhibitors
      remain unclear. We measured the sensitivity of contraction of the rat tail artery
      to intracellular Ca2+ in a model of polymicrobial septic shock. At 22 h after
      cecal ligation and puncture (CLP), rats were treated with an anti-inflammatory
      glucocorticoid (dexamethasone, 1 mg/kg ip), an inducible NOS inhibitor (L
      canavanine, 100 mg/kg ip), or saline. At 24 h after CLP, endothelium-denuded,
      perfused segments of tail artery were loaded with the intracellular Ca2+
      sensitive dye fura 2 in vitro. Intracellular Ca2+ concentration and perfusion
      pressure were measured simultaneously. The rightward shift of the perfusion
      pressure-intracellular Ca2+ mobilization curve after norepinephrine stimulation
      subsequent to CLP indicates decreased intracellular Ca2+ sensitivity of
      contraction. The relation was restored by dexamethasone (which also restored in
      vivo blood pressure and flow), but not by L-canavanine (which restored perfusion
      pressure by further mobilization of intracellular Ca2+). We conclude that CLP
      lowers vasomotion by lowering intracellular Ca2+ sensitivity, which can be
      restored with glucocorticoid treatment. The involvement of inducible NOS does not
      solely account for the sepsis-induced reduction in Ca2+ sensitivity of
      contraction.

PMID- 16603691
TI  - Role of superoxide and angiotensin II suppression in salt-induced changes in
      endothelial Ca2+ signaling and NO production in rat aorta.
AB  - Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or
      changed to a high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular
      Ca2+ ([Ca2+]i) in response to methacholine (10 microM) and histamine (10 microM)
      were significantly attenuated in aortic endothelial cells from rats fed a HS
      diet, whereas thapsigargin (10 microM)-induced increases in [Ca2+]i were
      unaffected. Methacholine-induced nitric oxide (NO) production was eliminated in
      endothelial cells of aortas from rats fed a HS diet. Low-dose ANG II infusion (5
      ng x kg(-1) x min(-1) iv) for 3 days prevented impaired [Ca2+]i signaling
      response to methacholine and histamine and restored methacholine-induced NO
      production in aortas from rats on a HS diet. Adding Tempol (500 microM) to the
      tissue bath to scavenge superoxide anions increased NO release and caused
      N(omega)-nitro-L-arginine methyl ester-sensitive vascular relaxation in aortas
      from rats fed a HS diet but had no effect on methacholine-induced Ca2+ responses.
      Chronic treatment with Tempol (1 mM) in the drinking water restored NO release,
      augmented vessel relaxation, and increased methacholine-induced Ca2+ responses
      significantly in aortas from rats on a HS diet but not in aortas from rats on a
      LS diet. These findings suggest that 1) agonist-induced Ca2+ responses and NO
      levels are reduced in aortas of rats on a HS diet; 2) increased vascular
      superoxide levels contribute to NO destruction, and, eventually, to impaired Ca2+
      signaling in the vascular endothelial cells; and 3) reduced circulating ANG II
      levels during elevated dietary salt lead to elevated superoxide levels, impaired
      endothelial Ca2+ signaling, and reduced NO production in the endothelium.

PMID- 16603692
TI  - Sex-related dimorphic response of HIF-1 alpha expression in myocardial ischemia.
AB  - Hypoxia-inducible factor-1 alpha (HIF-1 alpha) plays a role in a number of cell
      protective pathways after ischemia. There are clear sex-related differences in
      the remodeling process, and hearts from males tend to dilate in response to
      pathological loads and ischemia to a greater degree than do hearts from females.
      Thus we hypothesized that there would be a sex-related dimorphic response of HIF
      1 alpha to an ischemic event. Male and female rats were euthanized 5 and 24 h
      after coronary ligation (M-MI and F-MI; MI, myocardial ischemia), and HIF-1 alpha
      expression was determined by immunohistochemistry, Western blot, and quantitative
      RT-PCR. Sham-operated male and female animals served as controls (M-SH and F-SH).
      In the ischemic area, histochemical analysis at 5 h showed that HIF was expressed
      in 33% of cell nuclei in M-MI and in 55% in F-MI. At 24 h, HIF expression
      increased to 49% in M-MI and to 82% in F-MI (P < 0.05 vs. SH and also M-MI vs. F
      MI). This difference was not only statistically significant between the two sexes
      at 24 h but also within each sex at 5 and 24 h after ligation. Western blots
      confirmed that, at 24 h after ischemia, HIF protein increased significantly in
      both male and female hearts relative to sham-operated animals but that the
      increase in females was 60% greater than that seen in males. mRNA expression of
      HIF was significantly increased at 24 h in F-MI versus M-MI and sham-operated
      animals. Expression of downstream HIF target genes (heme oxygenase and brain
      natriuretic peptide) was increased in proportion to the levels of HIF expression.
      These data suggest a novel cellular mechanism to explain the sex-related
      dimorphic response to ischemia and also the possibility that exogenous modulation
      of HIF might represent a new therapeutic approach to preventing left ventricular
      remodeling.

PMID- 16603693
TI  - PPAR-gamma agonists decrease hyperhomcysteinemia and cardiac dysfunction: new
      hope for ailing diabetic hearts?

PMID- 16603694
TI  - Having a heart attack? Avoid the "HETE"!

PMID- 16603695
TI  - A novel strategy for increasing wall thickness of coronary venules prior to
      retroperfusion.
AB  - The sudden exposure of veins to arterial pressures during coronary venous
      retroperfusion may cause rupture of small venules. Our rationale is to first
      occlude the coronary vein, which will cause an increase in pressure intermediate
      to arterial and venous values, and hence lead to remodeling and increased wall
      thickness of the veins prior to retroperfusion. To accomplish this objective,
      five pigs were subjected to left anterior descending (LAD) vein ligation while
      six pigs served as sham. Myocardial tissue samples were obtained from the area
      adjacent to the LAD vein at four transmural locations of the left ventricular
      free wall: epicardial surface, subepicardium, midmyocardium, and endocardium.
      Arterioles and venules from the experimental and sham control groups were
      photographed, and the following measurements were made: inner and outer
      circumferences, inner and outer areas, major and minor diameters, and intima
      media thickness. Each vessel was categorized in four different orders according
      to lumen diameter. Our results show that intima-media thickness was larger in the
      experimental group in all four regions of the heart and in all four orders of the
      vessels, although venules from the epicardial region showed the largest increase
      in thickness. The intima-media thickness-to-radius ratio was also larger in the
      experimental group and decreased from epicardial to endocardial region of the
      heart and from order 1 to order 4 of the vessels. The present study provides a
      rationale for the development of coronary retroperfusion strategy that avoids
      vessel rupture and hemorrhage in the postcapillary venules.

PMID- 16603696
TI  - CRP promotes monocyte-endothelial cell adhesion via Fcgamma receptors in human
      aortic endothelial cells under static and shear flow conditions.
AB  - Monocyte-endothelial cell adhesion is a key early event in atherogenesis. C
      reactive protein (CRP), a cardiovascular risk marker, is known to stimulate ICAM
      and VCAM in human aortic endothelial cells (HAEC) and induces monocyte
      endothelial cell adhesion. In this study, we examined the mechanisms by which
      native CRP promotes monocyte-endothelial cell adhesion under static conditions
      and tested the effect of CRP on adhesion under shear flow. Incubation of HAEC
      with CRP (>25 microg/ml) upregulated NF-kappaB activity, and this resulted in a
      significant increase in ICAM (54% increase, P<0.001), VCAM (41% increase,
      P<0.01), and monocyte-endothelial cell adhesion (44% increase, P<0.02) compared
      with those of control. Preincubation with antibodies to CD32 and CD64 but not
      CD16 effectively inhibited this activation. Blocking NF-kappaB activity with
      inhibitors or a dominant negative inhibitory kappaB significantly decreased ICAM,
      VCAM upregulation, and subsequent monocyte-endothelial cell adhesion.
      Preincubation with antibodies to CD32 and CD64 or transient transfection with
      small interference RNA to CD32 attenuated CRP-induced NF-kappaB activity, ICAM,
      VCAM, and monocyte-endothelial cell adhesion under static conditions. Also, the
      Syk kinase inhibitor piceatannol and MG-132, a proteasome degradation inhibitor,
      produced similar attenuation in NF-kappaB activity, ICAM, VCAM, and adhesion.
      Furthermore, CRP-activated endothelial cells supported monocyte rolling, arrest,
      and transmigration in shear flow (2 dyn/cm2), and this was also inhibited by
      preincubation with antibodies to CD32 and CD64. Thus, in HAEC, CRP upregulates
      monocyte-endothelial adhesion by activation of NF-kappaB through engaging the
      Fcgamma receptors CD32 and CD64.

PMID- 16603697
TI  - Cytokines produced by bone marrow cells can contribute to functional improvement
      of the infarcted heart by protecting cardiomyocytes from ischemic injury.
AB  - It is well known that the implantation of bone marrow mononuclear cells (BM-MNCs)
      into ischemic hearts can induce angiogenesis and improve cardiac function after
      myocardial infarction, but the precise mechanisms of these actions are unclear.
      We hypothesize that the cytokines produced by BM-MNCs play a key role in this
      cell-based therapy. BM-MNCs from rats were cultured under normoxic or hypoxic (1%
      O2) conditions for 24 h, and then supernatants were collected for study. ELISA
      and Western blotting analysis showed that various cytokines, including VEGF, IL-1
      beta, PDGF, and IGF-1, were produced from BM-MNCs, some of which were enhanced
      significantly under hypoxia stimulation. When compared with a control blank
      medium, the supernatants of BM-MNCs cultured under normoxic or hypoxic conditions
      inhibited apoptosis significantly and preserved the contractile capacity of
      isolated adult rat cardiomyocytes in vitro (P < 0.05). Using a rat model of acute
      myocardial infarction, we injected the supernatants of BM-MNCs or control medium
      intramyocardially on day 0 and then intraperitoneally on days 2, 4, and 6 after
      infarction. When compared with the control medium, the supernatants of BM-MNCs
      cultured under both normoxic or hypoxic conditions increased the microvessel
      density and decreased the fibrotic area in the infarcted myocardium
      significantly, contributing to remarkable improvement in cardiac function.
      Various cytokines were produced by BM-MNCs, and these cytokines contributed to
      functional improvement of the infarcted heart by directly preserving the
      contractile capacity of the myocardium, inhibiting apoptosis of cardiomyocytes,
      and inducing therapeutic angiogenesis of the infarcted heart.

PMID- 16603698
TI  - Myocardial protection by pioglitazone, atorvastatin, and their combination:
      mechanisms and possible interactions.
AB  - We assessed 1) whether pretreatment before ischemia with pioglitazone (Pio)
      limits infarct size (IS) and whether this protective effect is due to nitric
      oxide synthase (NOS) and/or prostaglandin production, as has been shown for
      atorvastatin (ATV); and 2) whether Pio and ATV have synergistic effects on
      myocardial protection. Sprague-Dawley rats received oral ATV (10 mg.kg-1.day-1),
      Pio (10 mg.kg-1.day-1), their combination (Pio+ATV), or water alone for 3 days.
      Additional rats received Pio (10 mg.kg-1.day-1) for 3 days and intravenous SC
      58125 [a cyclooxygenase-2 (COX-2) inhibitor] or SC-560 (a COX-1 inhibitor) 15 min
      before ischemia. Rats underwent 30 min of myocardial ischemia and 4 h of
      reperfusion, or hearts were harvested for analysis. IS in the Pio and in the ATV
      groups was significantly smaller than in the sham-treated group. IS in the
      Pio+ATV group was smaller than in all other groups (P<0.001 vs. each group). The
      protective effect of Pio was abrogated by SC-58125 but not by SC-560. Pio, ATV,
      and Pio + ATV increased the expression and activity of cytosolic phospholipase A2
      (cPLA2) and COX-2. ATV increased phosphorylated-Akt, phosphorylated-endothelial
      NOS (P-eNOS), inducible NOS, and COX-2 levels. In contrast, Pio caused an
      insignificant increase in myocardial levels of phosphorylated-Akt but did not
      change P-eNOS and iNOS expression. In conclusion, the IS-limiting effects of Pio
      and ATV involve COX-2. However, the upstream steps differ. ATV induced eNOS
      phosphorylation and iNOS, cPLA2, and COX-2 expression, whereas Pio induced mainly
      the expression and activity of cPLA2. The effects of Pio and ATV were additive.

PMID- 16603699
TI  - Developmental changes in hemodynamics of uterine artery, utero- and
      umbilicoplacental, and vitelline circulations in mouse throughout gestation.
AB  - In human pregnancy, abnormal placental hemodynamics likely contribute to the
      etiology of early-onset preeclampsia and fetal intrauterine growth restriction.
      The mouse is increasingly being deployed to study normal and abnormal mammalian
      placental development, yet the placental hemodynamics in normal pregnancy in mice
      is currently unknown. We used ultrasound biomicroscopy to noninvasively image and
      record Doppler blood velocity waveforms from the maternal and embryonic placental
      circulations in mice throughout gestation. In the uterine artery, peak systolic
      velocity (PSV) increased significantly from 23+/-2 (SE) to 59+/-3 cm/s, and end
      diastolic velocity (EDV) increased from 7+/-1 to 28+/-2 cm/s in nonpregnant
      versus full-term females so that the uterine arterial resistance index (RI)
      decreased from 0.70+/-0.02 to 0.53+/-0.02. Velocities in the maternal arterial
      canal in the placenta were low and nearly steady and increased from 0.9+/-0.03
      cm/s at embryonic day 10.5 (E10.5) to 2.4+/-0.07 cm/s at E18.5. PSV in the
      umbilical artery increased steadily from 0.8+/-0.1 cm/s at E8.5 to 15+/-0.6 cm/s
      at E18.5, whereas PSV in the vitelline artery increased from 0.6+/-0.1 cm/s at
      E8.5 to 4+/-0.2 cm/s at E13.5 and then remained stable to term. In the umbilical
      artery, the EDV detection rate was 0% at <or=E14.5 and 94% at E18.5, and the RI
      decreased from 1 to 0.82+/-0.01 during this interval. We conclude that ultrasound
      biomicroscopy can be used to monitor placental hemodynamics during pregnancy in
      mice. These results provide novel information concerning the development of the
      vitelline and placental circulations in mice and reveal strong similarities in
      placental hemodynamics between mice and humans.

PMID- 16603700
TI  - Activation of brain renin-angiotensin-aldosterone system by central sodium in
      Wistar rats.
AB  - Functional studies indicate that the sympathoexcitatory and pressor responses to
      an increase in cerebrospinal fluid (CSF) [Na+] by central infusion of Na+-rich
      artificial cerebrospinal fluid (aCSF) in Wistar rats are mediated in the brain by
      mineralocorticoid receptor (MR) activation, ouabain-like compounds (OLC), and AT1
      receptor stimulation. In the present study, we examined whether increasing CSF
      [Na+] by intracerebroventricular infusion of Na+-rich aCSF activates MR and
      thereby increases OLC and components of the renin-angiotensin system in the
      brain. Male Wistar rats received via osmotic minipump an intracerebroventricular
      infusion of aCSF or Na+-rich aCSF, in some groups combined with
      intracerebroventricular infusion of spironolactone (100 ng/h), antibody Fab
      fragments (to bind OLC), or as control gamma-globulins. After 2 wk of infusion,
      resting blood pressure and heart rate were recorded, OLC and aldosterone content
      in the hypothalamus were assessed by a specific ELISA or radioimmunoassay, and
      angiotensin-converting enzyme (ACE) and AT1-receptor binding densities in various
      brain nuclei were measured by autoradiography using 125I-labeled 351 A and 125I
      labeled ANG II. When compared with intracerebroventricular aCSF,
      intracerebroventricular Na+-rich aCSF increased CSF [Na+] by approximately 5
      mmol/l, mean arterial pressure by approximately 20 mmHg, heart rate by
      approximately 65 beats/min, and hypothalamic content of OLC by 50% and of
      aldosterone by 33%. Intracerebroventricular spironolactone did not affect CSF
      [Na+] but blocked the Na+-rich aCSF-induced increases in blood pressure and heart
      rate and OLC content. Intracerebroventricular Na+-rich aCSF increased ACE and AT1
      receptor-binding densities in several brain nuclei, and Fab fragments blocked
      these increases. These data indicate that in Wistar rats, a chronic increase in
      CSF [Na+] may increase hypothalamic aldosterone and activate CNS pathways
      involving MR, and OLC, leading to increases in AT1-receptor and ACE densities in
      brain areas involved in cardiovascular regulation and hypertension.

PMID- 16603701
TI  - Quantifying cardiac sympathetic and parasympathetic nervous activities using
      principal dynamic modes analysis of heart rate variability.
AB  - The ratio between low-frequency (LF) and high-frequency (HF) spectral power of
      heart rate has been used as an approximate index for determining the autonomic
      nervous system (ANS) balance. An accurate assessment of the ANS balance can only
      be achieved if clear separation of the dynamics of the sympathetic and
      parasympathetic nervous activities can be obtained, which is a daunting task
      because they are nonlinear and have overlapping dynamics. In this study, a
      promising nonlinear method, termed the principal dynamic mode (PDM) method, is
      used to separate dynamic components of the sympathetic and parasympathetic
      nervous activities on the basis of ECG signal, and the results are compared with
      the power spectral approach to assessing the ANS balance. The PDM analysis based
      on the 28 subjects consistently resulted in a clear separation of the two nervous
      systems, which have similar frequency characteristics for parasympathetic and
      sympathetic activities as those reported in the literature. With the application
      of atropine, in 13 of 15 supine subjects there was an increase in the sympathetic
      to-parasympathetic ratio (SPR) due to a greater decrease of parasympathetic than
      sympathetic activity (P=0.003), and all 13 subjects in the upright position had a
      decrease in SPR due to a greater decrease of sympathetic than parasympathetic
      activity (P<0.001) with the application of propranolol. The LF-to-HF ratio
      calculated by the power spectral density is less accurate than the PDM because it
      is not able to separate the dynamics of the parasympathetic and sympathetic
      nervous systems. The culprit is equivalent decreases in both the sympathetic and
      parasympathetic activities irrespective of the pharmacological blockades. These
      findings suggest that the PDM shows promise as a noninvasive and quantitative
      marker of ANS imbalance, which has been shown to be a factor in many cardiac and
      stress-related diseases.

PMID- 16603702
TI  - Premature senescence of endothelial cells: Methusaleh's dilemma.
AB  - Senescence has been considered a programmed cellular response, parallel to
      apoptosis, that is turned on when a cell reaches Hayflick's limit. Once cells
      enter the senescence program, they cease to proliferate and undergo a series of
      morphological and functional changes. Studies support a central role for Rb
      protein in controlling this process after it receives senescent signals from the
      p53 and p16 pathways. Cellular senescence is considered an essential contributor
      to the aging process and has been shown to be an important tumor suppression
      mechanism. In addition, emerging evidence suggests that senescence may also be
      involved in the pathogenesis of stem cell dysfunction and chronic human diseases.
      Under these circumstances cells undergo stress-induced premature senecence, which
      has several specific features. Focusing on endothelial cells, we discuss recent
      advances in our understanding of the stresses and their pathways that prompt the
      premature senescence response, evaluate their correlation with the apoptotic
      response, and examine their links to the development of chronic diseases and the
      impaired function of endothelial progenitor cells, with the emphasis on
      vasculopathy. Emerging novel therapeutic interventions based on recent
      experimental findings are also reviewed.

PMID- 16603703
TI  - Metabolic responsiveness to insulin in the diabetic heart.

PMID- 16603704
TI  - Mitochondrial ATP-sensitive potassium channels and mitochondrial protein kinase
      C: sometimes it's good to have a close neighbor.

PMID- 16603705
TI  - Adventitial delivery of dominant-negative p67phox attenuates neointimal
      hyperplasia of the rat carotid artery.
AB  - Several essential components of NADPH oxidase, including p22phox, gp91phox (nox2)
      and its homologs nox1 and nox4, p47phox, p67phox, and rac1, are present in the
      vasculature. We previously reported that p67phox is essential for adventitial
      fibroblast NADPH oxidase O2- production. Thus we postulated that inhibition of
      adventitial p67phox activity would attenuate angioplasty-induced hyperplasia. To
      test this hypothesis, we treated the adventitia of carotid arteries with a
      control adenovirus (Ad-control), a virus expressing dominant-negative p67phox (Ad
      p67dn), or a virus expressing a competitive peptide (gp91ds) targeting the
      p47phox-gp91phox interaction (Ad-gp91ds). Common carotid arteries (CCAs) from
      male Sprague-Dawley rats were transfected with Ad-control, Ad-p67dn, or Ad-gp91ds
      in pluronic gel. After 2 days, a 2-F (Fogarty) catheter was used to injure CCAs
      in vivo. After 14 days, CCAs were perfusion-fixed and analyzed. In 13
      experiments, digital morphometry suggested a reduction of neointimal hyperplasia
      with Ad-p67dn compared with Ad-control; however, the reduction did not reach
      statistical significance (P = 0.058). In contrast, a significant reduction was
      achieved with Ad-gp91ds (P = 0.006). No changes in medial area or remodeling were
      observed with either treatment. Moreover, adventitial fibroblast proliferation in
      vitro was inhibited by Ad-gp91ds but not by Ad-p67dn, despite confirmation that
      Ad-p67dn inhibits NADPH oxidase in fibroblasts. These data appear to suggest that
      a multicomponent vascular NADPH oxidase plays a role in neointimal hyperplasia.
      However, inhibition of p47phox may be more effective than inhibition of p67phox
      at attenuating neointimal growth.

PMID- 16603706
TI  - Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an
      inhibitory interaction with GATA4.
AB  - Pathological cardiac hypertrophy is considered a precursor to clinical heart
      failure. Understanding the transcriptional regulators that suppress the
      hypertrophic response may have profound implications for the treatment of heart
      disease. We report the generation of transgenic mice that overexpress the
      transcription factor CHF1/Hey2 in the myocardium. In response to the alpha
      adrenergic agonist phenylephrine, they show marked attenuation in the
      hypertrophic response compared with wild-type controls, even though blood
      pressure is similar in both groups. Isolated myocytes from transgenic mice
      demonstrate a similar resistance to phenylephrine-induced hypertrophy in vitro,
      providing further evidence that the protective effect of CHF1/Hey2 is mediated at
      the myocyte level. Induction of the hypertrophy marker genes ANF, BNP, and beta
      MHC in the transgenic cells is concurrently suppressed in vivo and in vitro,
      demonstrating that the induction of hypertrophy-associated genes is repressed by
      CHF1/Hey2. Transfection of CHF1/Hey2 into neonatal cardiomyocytes suppresses
      activation of an ANF reporter plasmid by the transcription factor GATA4, which
      has previously been shown to activate a hypertrophic transcriptional program.
      Furthermore, CHF1/Hey2 binds GATA4 directly in coimmunoprecipitation assays and
      inhibits the binding of GATA4 to its recognition sequence within the ANF
      promoter. Our findings demonstrate that CHF1/Hey2 functions as an
      antihypertrophic gene, possibly through inhibition of a GATA4-dependent
      hypertrophic program.

PMID- 16603707
TI  - Oxygen reperfusion is limited in the postischemic hypertrophic myocardium.
AB  - Studies have shown that hypertrophied hearts are unusually vulnerable to
      ischemia. Compromised O2 supply has been postulated as a possible explanation for
      this phenomenon on the basis of elongated O2 diffusion distance and altered
      coronary vasculature found in hypertrophied myocardium. To examine the postulate,
      perfused heart experiments followed the metabolic and functional responses of
      hypertrophic myocardium to ischemia. 1H/31P NMR was used to measure cellular
      oxygenation and energy level during ischemia-reperfusion. The left ventricles
      from spontaneously hypertensive rats (SHR) were enlarged by 48%. With this
      moderate degree of hypertrophy, cellular O2 and energy levels were normal during
      baseline perfusion. After an ischemic episode, however, cellular O2 was severely
      deprived in the SHR hearts compared with the normal hearts. Depressed
      postischemic O2 reperfusion correlated well with depressed energetic and
      functional recovery. The results from the current study thus demonstrate a
      critical relationship between reperfused O2 level and functional recovery in
      hypertrophic myocardium. The role of reperfused O2, however, is time dependent.
      During early reperfusion, factor(s) other than O2 appear to limit functional
      recovery. It is when the mechanical function of the heart approaches a new steady
      state that O2 becomes a dominant factor. Meanwhile, the finding of a normal O2
      level in preischemic SHR hearts defies the notion of preexisting hypoxia as a
      primer of ischemic damage.

PMID- 16603708
TI  - Measurement of myofilament calcium sensitivity at physiological temperature in
      intact cardiac trabeculae.
AB  - Cardiac contraction-relaxation coupling is determined by both the free
      intracellular calcium concentration ([Ca2+]i) and myofilament properties. We set
      out to develop a technique where we could assess these parameters (twitch and
      steady-state force [Ca2+]i) under near physiological conditions. Bis-fura-2 was
      iontophorically introduced into ultrathin rat trabeculae preparations to monitor
      the [Ca2+]i, and steady-state contractures were achieved by using a modified
      Krebs-Henseleit solution containing high K+. During K+ contractures, the very
      slow changes in [Ca2+]i and force development were in equilibrium and allowed for
      the construction of a steady-state, force-[Ca2+]i relationship. Twitch
      contractions before and after this myofilament calcium sensitivity assessment
      were unaltered, and this protocol could be repeated several times. For the first
      time, this novel protocol allows us to measure myofilament calcium sensitivity
      under physiological temperature. Not only do the data so obtained allow us to
      assess myofilament calcium sensitivity, the data also will allow us, in the same
      preparation under nearly identical conditions, to compare the dynamic to the
      steady-state, force-calcium relationship. To test whether the steady-state
      relationship between force and calcium in our novel protocol reproduces expected
      changes, we determined this relationship in the presence of isoproterenol and
      under acidosis and alkalosis. As expected, beta-adrenergic stimulation resulted
      in an increase of calcium amplitude and twitch force and a desensitization of the
      myofilaments as indicated by a rightward shift of the obtained steady-state,
      force-calcium relationship. An increase in pH shifted the curve leftward, whereas
      a decrease in pH resulted in the expected rightward shift.

PMID- 16603709
TI  - Brain structure predicts the learning of foreign speech sounds.
AB  - Previous work has shown a relationship between parietal lobe anatomy and
      nonnative speech sound learning. We scanned a new group of phonetic learners
      using structural magnetic resonance imaging and diffusion tensor imaging. Voxel
      based morphometry indicated higher white matter (WM) density in left Heschl's
      gyrus (HG) in faster compared with slower learners, and manual segmentation of
      this structure confirmed that the WM volume of left HG is larger in the former
      compared with the latter group. This finding was replicated in a reanalysis of
      the original groups tested in Golestani and others (2002, Anatomical correlates
      of learning novel speech sounds. Neuron 35:997-1010). We also found that faster
      learners have a greater asymmetry (left > right) in parietal lobe volumes than
      slower learners and that the right insula and HG are more superiorly located in
      slower compared with faster learners. These results suggest that left auditory
      cortex WM anatomy, which likely reflects auditory processing efficiency, partly
      predicts individual differences in an aspect of language learning that relies on
      rapid temporal processing. It also appears that a global displacement of
      components of a right hemispheric language network, possibly reflecting
      individual differences in the functional anatomy and lateralization of language
      processing, is predictive of speech sound learning.

PMID- 16603710
TI  - Cytoarchitectonic analysis of the human extrastriate cortex in the region of
      V5/MT+: a probabilistic, stereotaxic map of area hOc5.
AB  - Functional imaging studies identified a motion-sensitive area (V5/MT+) in the
      vicinity of the posterior branch of the inferior temporal sulcus that has no
      correlate in any classical cytoarchitectonic map. The aim of the present study
      was to identify a cytoarchitectonic correlate of this region in 10 human
      postmortem brains and to provide a probability map of this area. Observer
      independent mapping revealed an area, hOc5 (h for human, Oc for occipital lobe),
      that has a broad layer III, a high cell density in layer II/III, and a low one in
      layer V. Most of area hOc5 is found in the depths of the anterior occipital
      sulcus and the anterior parts of either the inferior lateral occipital or the
      inferior occipital sulcus. After 3-dimensional reconstruction and registration to
      a standard reference space, a probability map of the area measured the individual
      variability of its size and location. The mean spatial locations of area hOc5 are
      -43, -73, 10 (left) and 49, -70, 11 (right). The locations and their
      relationships to sulci strongly suggest that hOc5 is the cytoarchitectonic
      correlate of human V5/MT+. This hypothesis was supported by comparing the
      cytoarchitectonic probabilistic map with results from a functional imaging study.

PMID- 16603711
TI  - The effect of temporal context on the sustained pitch response in human auditory
      cortex.
AB  - Recent neuroimaging studies have shown that activity in lateral Heschl's gyrus
      covaries specifically with the strength of musical pitch. Pitch strength is
      important for the perceptual distinctiveness of an acoustic event, but in complex
      auditory scenes, the distinctiveness of an event also depends on its context. In
      this magnetoencephalography study, we evaluate how temporal context influences
      the sustained pitch response (SPR) in lateral Heschl's gyrus. In 2 sequences of
      continuously alternating, periodic target intervals and a more irregular baseline
      interval, the distinctiveness of the target was decreased in 1 of 2 ways--either
      by increasing the pitch strength of the baseline or by decreasing the pitch
      strength of the target. The results show that the amplitude of the SPR increases
      monotonically with the distinctiveness of the target. Moreover, SPR amplitude is
      greater for the sequence, where the pitch strength of the target is varied,
      compared with the condition, where the baseline is varied. Two subsequent
      experiments show that the amplitude of the SPR increases as duty cycle decreases,
      in a pitch "strength" contrast and in a pitch "value" contrast. These results
      indicate that the SPR adapts to recent stimulus history, enhancing the response
      to rare and brief events.

PMID- 16603712
TI  - Word reading and posterior temporal dysfunction in amnestic mild cognitive
      impairment.
AB  - Patient studies that combine functional magnetic resonance imaging with
      chronometric analysis of language dysfunction may reveal the critical
      contribution of brain areas to language processes as well as shed light on
      disease pathogenesis. In amnestic mild cognitive impairment (MCI), a prodromal
      stage of Alzheimer's disease, we examined whether the brain system for
      associative-semantic judgments with words or with pictures is affected and how
      this relates to off-line chronometric analysis of word reading and picture
      naming. A consecutive memory clinic-based series of 13 amnestic MCI patients as
      well as 13 matched controls participated. One area, the lower bank of the
      posterior third of the left superior temporal sulcus (STS), showed a significant
      group-by-task interaction: In controls, it was activated during the associative
      semantic condition with words compared with the visuoperceptual control condition
      but not when the same tasks were compared with pictures as input. In MCI, this
      word-specific activation was significantly reduced. Response amplitude correlated
      (r = 0.90) with the steepness of the slope of the time-accuracy curve for word
      reading. Our data provide converging evidence for a critical contribution of the
      lower bank of the left posterior STS to mapping word form onto word meaning
      (lexical-semantic retrieval).

PMID- 16603713
TI  - Spatiotemporal dynamics of the functional architecture for gain fields in
      inferior parietal lobule of behaving monkey.
AB  - Intrinsic optical imaging has revealed a representation of eye position smoothly
      mapped across the surface of the inferior parietal lobule in behaving monkeys. We
      demonstrate here that blood vessels imaged along with the cortex have large
      signals tuned sometimes, but not always, to match the surrounding tissue. The
      relationship between the vessels and surrounding tissue in both space and time
      was explored using independent component analysis (ICA). Working only with single
      trial data, ICA discovered a sequence of regions corresponding to the vascular
      propagation of activated signals from remote loci into the blood vessels. The
      vascular signals form a novel map of cortical function--the functional
      angioarchitecture--superimposed upon the cortical functional architecture.
      Furthermore, the incorporation of temporal aspects in optical data permitted the
      tuning of the inferior parietal lobule to be tracked in time through the task,
      demonstrating the expression of unusual tuning properties that might be exploited
      for higher cognitive functions.

PMID- 16603714
TI  - Neuroanatomical correlates of memory deficits in tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is a multisystem syndrome classically associated
      with the occurrence of focal brain dysplasias. We used structural magnetic
      resonance imaging to test for neuroradiological abnormalities in TSC (tubers,
      white matter lesions, and subependymal nodules) and to explore the relationships
      between these lesions and computational morphometric abnormalities of gray and
      white matter distribution. We tested memory function in TSC and investigated the
      relationship between memory function and both morphometric variation and lesion
      load. Patients demonstrated deficits bilaterally in volume of subcortical gray
      matter regions including thalamus, basal ganglia, insula, and cerebellum, as well
      as white matter deficits bilaterally in intrahemispheric tracts. Morphometric
      deficits could not be explained as local effects of lesions. Patients
      demonstrated deficits in executive working memory and recall memory, sparing
      recognition. Structure-function mapping showed long-term and working memory
      function was positively correlated with gray matter density (in thalamus, caudate
      nucleus, and frontal cortex) but not with lesion load. The neuroanatomical
      endophenotype of TSC is more extensive than previously recognized and comprises
      abnormalities in the distribution of gray and white matter in addition to
      classical lesions. Normal intelligence quotient patients with TSC show a profile
      of long-term and working memory impairment that is related to gray matter
      deficits in thalamus and basal ganglia components of fronto-striatal circuits.

PMID- 16603715
TI  - RDE-4 preferentially binds long dsRNA and its dimerization is necessary for
      cleavage of dsRNA to siRNA.
AB  - In organisms ranging from Arabidopsis to humans, Dicer requires dsRNA-binding
      proteins (dsRBPs) to carry out its roles in RNA interference (RNAi) and micro-RNA
      (miRNA) processing. In Caenorhabditis elegans, the dsRBP RDE-4 acts with Dicer
      during the initiation of RNAi, when long dsRNA is cleaved to small interfering
      RNAs (siRNAs). RDE-4 is not required in subsequent steps, and how RDE-4
      distinguishes between long dsRNA and short siRNA is unclear. We report the first
      detailed analysis of RDE-4 binding, using purified recombinant RDE-4 and various
      truncated proteins. We find that, similar to other dsRBPs, RDE-4 is not sequence
      specific. However, consistent with its in vivo roles, RDE-4 binds with higher
      affinity to long dsRNA. We also observe that RDE-4 is a homodimer in solution,
      and that the C-terminal domain of the protein is required for dimerization. Using
      extracts from wild-type and rde-4 mutant C. elegans, we show that the C-terminal
      dimerization domain is required for the production of siRNA. Our findings suggest
      a model for RDE-4 function during the initiation of RNAi.

PMID- 16603716
TI  - Identification of RNA-binding proteins that regulate FGFR2 splicing through the
      use of sensitive and specific dual color fluorescence minigene assays.
AB  - We have developed a series of fluorescent splicing reporter minigenes for the
      establishment of cell-based screens to identify splicing regulatory proteins. A
      key technical advance in the application of these reporters was the use of two
      different fluorescent proteins: EGFP and monomeric Red Fluorescent Protein
      (mRFP). Through establishment of stable cell lines expressing such dual color
      fluorescent reporters, these minigenes can be used to perform enhanced screens
      for splicing regulatory proteins. As an example of such applications we generated
      fluorescent minigenes that can be used to determine the splicing of mutually
      exclusive FGFR2 exons IIIb and IIIc by flow cytometry. One minigene contained a
      coding sequence for EGFP whose translation was dependent on splicing of exon
      IIIb, whereas a second minigene required exon IIIc splicing for translation of an
      mRFP coding sequence. Stable incorporation of both minigenes into cells that
      express endogenous FGFR2-IIIb or FGFR2-IIIc resulted in EGFP or mRFP
      fluorescence, respectively. Cells stably transfected with both minigenes were
      used to screen a panel of cDNAs encoding known splicing regulatory proteins, and
      several were identified that induced a switch in splicing that could be detected
      specifically by an increase in green, but not red, fluorescence. We further
      demonstrated additional minigenes that can be used in dual color fluorescent
      screens for identification of splicing regulatory proteins that function through
      specific intronic splicing enhancer elements (ISEs). The methods and minigene
      designs described here should be adaptable for broader applications in
      identification of factors and mechanisms involved in alternative splicing of
      numerous other gene transcripts.

PMID- 16603717
TI  - hnRNP A1 associates with telomere ends and stimulates telomerase activity.
AB  - Telomerase is a ribonucleoprotein enzyme complex that reverse-transcribes an
      integral RNA template to add short DNA repeats to the 3'-ends of telomeres. G
      quadruplex structure in a DNA substrate can block its extension by telomerase. We
      have found that hnRNP A1--which was previously implicated in telomere length
      regulation--binds to both single-stranded and structured human telomeric repeats,
      and in the latter case, it disrupts their higher-order structure. Using an in
      vitro telomerase assay, we observed that depletion of hnRNP A/B proteins from 293
      human embryonic kidney cell extracts dramatically reduced telomerase activity,
      which was fully recovered upon addition of purified recombinant hnRNP A1. This
      finding suggests that hnRNP A1 functions as an auxiliary, if not essential,
      factor of telomerase holoenzyme. We further show, using chromatin
      immunoprecipitation, that hnRNP A1 associates with human telomeres in vivo. We
      propose that hnRNP A1 stimulates telomere elongation through unwinding of a G
      quadruplex or G-G hairpin structure formed at each translocation step.

PMID- 16603718
TI  - Role of the glutathione metabolic pathway in lung cancer treatment and prognosis:
      a review.
AB  - Inherent and acquired drug resistance is a cause of chemotherapy failure, and
      pharmacogenomic studies have begun to define gene variations responsible for
      varied drug metabolism, which influences drug efficacy. Platinum-based compounds
      are the most commonly used chemotherapeutic agents in the treatment of advanced
      stage lung cancer patients, and the glutathione metabolic pathway is directly
      involved in the detoxification or inactivation of platinum drugs. Consequently,
      genotypes corresponding to higher drug inactivation enzyme activity may predict
      poor treatment outcome. Available evidence is consistent with this hypothesis,
      although a definitive role for glutathione system genes in lung cancer prognosis
      needs to be elucidated. We present evidence supporting a role of the glutathione
      system in acquired and inherited drug resistance and/or adverse effects through
      the impact of either drug detoxification or drug inactivation, thus adversely
      effecting lung cancer treatment outcome. The potential application of glutathione
      system polymorphic genetic markers in identifying patients who may respond
      favorably, selecting effective antitumor drugs, and balancing drug efficacy and
      toxicity are discussed.

PMID- 16603719
TI  - Cyclin-dependent kinase pathways as targets for cancer treatment.
AB  - Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression
      and RNA transcription. A variety of genetic and epigenetic events cause universal
      overactivity of the cell cycle cdks in human cancer, and their inhibition can
      lead to both cell cycle arrest and apoptosis. However, built-in redundancy may
      limit the effects of highly selective cdk inhibition. Cdk4/6 inhibition has been
      shown to induce potent G1 arrest in vitro and tumor regression in vivo; cdk2/1
      inhibition has the most potent effects during the S and G2 phases and induces E2F
      transcription factor-dependent cell death. Modulation of cdk2 and cdk1 activities
      also affects survival checkpoint responses after exposure to DNA-damaging and
      microtubule-stabilizing agents. The transcriptional cdks phosphorylate the
      carboxy-terminal domain of RNA polymerase II, facilitating efficient
      transcriptional initiation and elongation. Inhibition of these cdks primarily
      affects the accumulation of transcripts with short half-lives, including those
      encoding antiapoptosis family members, cell cycle regulators, as well as p53 and
      nuclear factor-kappa B-responsive gene targets. These effects may account for
      apoptosis induced by cdk9 inhibitors, especially in malignant hematopoietic
      cells, and may also potentiate cytotoxicity mediated by disruption of a variety
      of pathways in many transformed cell types. Current work is focusing on
      overcoming pharmacokinetic barriers that hindered development of flavopiridol, a
      pan-cdk inhibitor, as well as assessing novel classes of compounds potently
      targeting groups of cell cycle cdks (cdk4/6 or cdk2/1) with variable effects on
      the transcriptional cdks 7 and 9. These efforts will establish whether the
      strategy of cdk inhibition is able to produce therapeutic benefit in the majority
      of human tumors.

PMID- 16603720
TI  - Atherosclerosis is enhanced by testosterone deficiency and attenuated by CETP
      expression in transgenic mice.
AB  - In this work, we investigated the impact of testosterone deficiency and
      cholesteryl ester transfer protein (CETP) expression on lipoprotein metabolism
      and diet-induced atherosclerosis. CETP transgenic mice and nontransgenic (nTg)
      littermates were studied 4 weeks after bilateral orchidectomy or sham operation.
      Castrated mice had an increase in the LDL fraction (+36% for CETP and +79% for
      nTg mice), whereas the HDL fraction was reduced (-30% for CETP and -11% for nTg
      mice). Castrated mice presented 1.7-fold higher titers of anti-oxidized LDL (Ox
      LDL) antibodies than sham-operated controls. Plasma levels of CETP, lipoprotein
      lipase, and hepatic lipase were not changed by castration. Kinetic studies showed
      no differences in VLDL secretion rate, VLDL-LDL conversion rate, or number of LDL
      and HDL receptors. Competition experiments showed lower affinity of LDL from
      castrated mice for tissue receptors. Diet-induced atherosclerosis studies showed
      that testosterone deficiency increased by 100%, and CETP expression reduced by
      44%, the size of aortic lesion area in castrated mice. In summary, testosterone
      deficiency increased plasma levels of apolipoprotein B-containing lipoproteins
      (apoB-LPs) and anti-OxLDL antibodies, decreased LDL receptor affinity, and
      doubled the size of diet-induced atherosclerotic lesions. The expression of CETP
      led to a milder increase of apoB-LPs and reduced atherosclerotic lesion size in
      testosterone-deficient mice.

PMID- 16603721
TI  - Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter.
AB  - Hepatic lipase (HL) plays a key role in the metabolism of plasma lipoproteins,
      and its level of activity requires tight regulation, given the association of
      both low and high levels with atherosclerosis and coronary artery disease.
      However, little is known about the factors responsible for HL expression. Here,
      we report that the human hepatic lipase gene (LIPC) promoter is regulated by
      hepatocyte nuclear factor 4alpha (HNF4alpha), peroxisome proliferator-activated
      receptor gamma coactivator-1alpha (PGC-1alpha), apolipoprotein A-I regulatory
      protein-1 (ARP-1), and hepatocyte nuclear factor 1alpha (HNF1alpha). Reporter
      analysis showed that HNF4alpha directly regulates the LIPC promoter via two newly
      identified direct repeat elements, DR1 and DR4. PGC-1alpha is capable of
      stimulating the HNF4alpha-dependent transactivation of the LIPC promoter. ARP-1
      displaces HNF4alpha from the DR1 site and blocks its ability to activate the LIPC
      promoter. Induction by HNF1alpha requires the HNF1 binding site and upon
      cotransfection with HNF4alpha leads to an additive effect. In addition, the in
      vivo relevance of HNF4alpha in LIPC expression is shown by the ability of the
      HNF4alpha antagonist Medica 16 to repress endogenous LIPC mRNA expression.
      Furthermore, disruption of Hnf4alpha in mice prevents the expression of HL mRNA
      in liver. The overall effect these transcription factors have on HL expression
      will ultimately depend on the interplay between these various factors and their
      relative intracellular concentrations.

PMID- 16603722
TI  - A novel enzyme-linked immunosorbent assay specific for high-molecular-weight
      adiponectin.
AB  - Human plasma contains at least three forms of adiponectin: a trimer, a hexamer,
      and a high-molecular-weight (HMW) multimer. We purified HMW adiponectin from
      human plasma using its affinity to gelatin and obtained monoclonal antibodies
      against it. On Western blot analysis, the reactivity of these monoclonal
      antibodies was shown to be restricted to a non-heat-denatured form of adiponectin
      molecules. On heating, the collagen-like domain of adiponectin molecules became
      denatured, and thus the trimer form could not be maintained. From these,
      monoclonal antibodies against HMW adiponectin were suggested to react with the
      intact trimer of adiponectin. With these monoclonal antibodies, we developed a
      sandwich ELISA system for quantifying adiponectin in human serum. Its specificity
      was verified by analysis of serum fractions separated by gel-filtration
      chromatography, and our ELISA system was found to be HMW adiponectin-specific.
      With this novel ELISA, the HMW adiponectin concentrations were 8.4 +/- 5.5
      microg/ml (mean +/- SD) in healthy women and 6.2 +/- 3.6 microg/ml in healthy
      men. Also, serum with a lower HMW adiponectin concentration was shown to have a
      lower HMW ratio (i.e., HMW adiponectin/total adiponectin).

PMID- 16603723
TI  - Effects of calcium-sensing receptor on the secretion of parathyroid hormone
      related peptide and its impact on humoral hypercalcemia of malignancy.
AB  - The extracellular calcium-sensing receptor (CaR) plays a key role in the defense
      against hypercalcemia by "sensing" extracellular calcium (Ca2+(o)) levels in the
      parathyroid and kidney, the key organs maintaining systemic calcium homeostasis.
      However, CaR function can be aberrant in certain pathophysiological states, e.g.,
      in some types of cancers known to produce humoral hypercalcemia of malignancy
      (HHM) in humans and animal models in which high Ca2+(o), via the CaR, produces a
      homeostatically inappropriate stimulation of parathyroid hormone-related peptide
      (PTHrP) secretion from these tumors. Increased levels of PTHrP set a cycle in
      motion whereby elevated systemic levels of Ca2+(o) resulting from its increased
      bone-resorptive and positive renal calcium-reabsorbing effects give rise to
      hypercalcemia, which in turn begets worsening hypercalcemia by stimulating
      further release of PTHrP by the cancer cells. I review the relationship between
      CaR activation and PTHrP release in normal and tumor cells giving rise to HHM
      and/or malignant osteolysis and the actions of the receptor on key cellular
      events such as proliferation, angiogenesis, and apoptosis of cancer cells that
      will favor tumor growth and osseous metastasis. I also illustrate diverse
      signaling mechanisms underlying CaR-stimulated PTHrP secretion and other cellular
      events in tumor cells. Finally, I raise several necessary questions to
      demonstrate the roles of the receptor in promoting tumors and metastases that
      will enable consideration of the CaR as a potential antagonizing/neutralizing
      target for the treatment of HHM.

PMID- 16603724
TI  - The molecular mechanism of EGF receptor activation in pancreatic beta-cells by
      thyrotropin-releasing hormone.
AB  - Thyrotropin-releasing hormone (TRH) and its receptor subtype TRH receptor-1
      (TRHR1) are found in pancreatic beta-cells, and it has been shown that TRH might
      have potential for autocrine/paracrine regulation through the TRHR1 receptor. In
      this paper, TRHR1 is studied to find whether it can initiate multiple signal
      transduction pathways to activate the epidermal growth factor (EGF) receptor in
      pancreatic beta-cells. By initiating TRHR1 G protein-coupled receptor (GPCR) and
      dissociated alphabetagamma-complex, TRH (200 nM) activates tyrosine residues at
      Tyr845 (a known target for Src) and Tyr1068 in the EGF receptor complex of an
      immortalized mouse beta-cell line, betaTC-6. Through manipulating the activation
      of Src, PKC, and heparin-binding EGF-like growth factor (HB-EGF), with
      corresponding individual inhibitors and activators, multiple signal transduction
      pathways linking TRH to EGF receptors in betaTC-6 cell line have been revealed.
      The pathways include the activation of Src kinase and the release of HB-EGF as a
      consequence of matrix metalloproteinase (MMP)-3 activation. Alternatively, TRH
      inhibited PKC activity by reducing the EGF receptor serine/threonine
      phosphorylation, thereby enhancing tyrosine phosphorylation. TRH receptor
      activation of Src may have a central role in mediating the effects of TRH on the
      EGF receptor. The activation of the EGF receptor by TRH in multiple circumstances
      may have important implications for pancreatic beta-cell biology.

PMID- 16603725
TI  - Melanin-concentrating hormone stimulates human growth hormone secretion: a novel
      effect of MCH on the hypothalamic-pituitary axis.
AB  - Melanin-concentrating hormone (MCH), a 19-amino acid orexigenic (appetite
      stimulating) hypothalamic peptide, is an important regulator of energy
      homeostasis. It is cleaved from its precursor prepro-MCH (ppMCH) along with
      several other neuropeptides whose roles are not fully defined. Because pituitary
      hormones such as growth hormone (GH), ACTH, and thyroid-stimulating hormone
      affect body weight and composition, appetite, insulin sensitivity, and
      lipoprotein metabolism, we investigated whether MCH exerts direct effects on the
      human pituitary to regulate energy balance using dispersed human fetal
      pituitaries (21-22 wk gestation) and cultured GH-secreting adenomas. We found
      that MCH receptor-1 (MCH-R1), but not MCH receptor-2, is expressed in both normal
      (fetal and adult) human pituitary tissues and in GH cell adenomas. MCH (10 nM)
      stimulated GH release from human fetal pituitary cultures by up to 62% during a 4
      h incubation (P < 0.05). Interestingly, neuropeptide EI (10 nM), which is also
      cleaved from ppMCH, increased human GH secretion by up to 124% in fetal
      pituitaries. A milder, albeit significant, induction of GH secretion by MCH (20%)
      was seen in cultured GH-secreting pituitary adenomas. A comparable stimulation of
      GH secretion was seen when cultured mouse pituitary cells were treated with MCH.
      Treatment of cultured GH adenoma cells with MCH (100 nM) induced extracellular
      signal-regulated kinases 1 and 2 phosphorylation, suggesting activation of MCH
      R1. In aggregate, these data suggest that MCH may regulate pituitary GH secretion
      and imply a potential cross-talk mechanism between appetite-regulating
      neuropeptides and pituitary hormones.

PMID- 16603728
TI  - Mechanisms of liver injury. III. Oxidative stress in the pathogenesis of
      hepatitis C virus.
AB  - Hepatitis C virus (HCV) is a major cause of viral hepatitis that can progress to
      hepatic fibrosis, steatosis, hepatocellular carcinoma, and liver failure. HCV
      infection is characterized by a systemic oxidative stress that is most likely
      caused by a combination of chronic inflammation, iron overload, liver damage, and
      proteins encoded by HCV. The increased generation of reactive oxygen and nitrogen
      species, together with the decreased antioxidant defense, promotes the
      development and progression of hepatic and extrahepatic complications of HCV
      infection. This review discusses the possible mechanisms of HCV-induced oxidative
      stress and its role in HCV pathogenesis.

PMID- 16603729
TI  - Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid
      oxidation.
AB  - Fatty liver disease (FLD), whether it is alcoholic FLD (AFLD) or nonalcoholic FLD
      (NAFLD), encompasses a morphological spectrum consisting of hepatic steatosis
      (fatty liver) and steatohepatitis. FLD has the inherent propensity to progress
      toward the development of cirrhosis and hepatocellular carcinoma. It is generally
      difficult to distinguish AFLD from NAFLD on morphological grounds alone despite
      the distinctions implied by these etiological designations. The indistinguishable
      spectrum of histological features of both AFLD and NAFLD suggests a possible
      convergence of pathogenetic mechanisms at some critical juncture that enables the
      progression of steatohepatitis toward cirrhosis and liver cancer. From a
      pathogenetic perspective, FLD may be considered a single disease with multiple
      etiologies. Excess energy consumption and reduced energy combustion appear to be
      critical events that culminate in lipid storage in the liver. Energy combustion
      in the liver is controlled by peroxisome proliferator-activated receptor (PPAR)
      alpha-regulated mitochondrial and peroxisomal fatty acid beta-oxidation systems
      and the microsomal omega-oxidation system. PPAR-alpha, a receptor for peroxisome
      proliferators, functions as a sensor for fatty acids (lipid sensor), and
      ineffective PPAR-alpha sensing can lead to reduced energy burning resulting in
      hepatic steatosis and steatohepatitis. Delineation of the pathogenetic aspects of
      FLD is necessary for developing novel therapeutic strategies for this disease.

PMID- 16603730
TI  - Effect of a selective chloride channel activator, lubiprostone, on
      gastrointestinal transit, gastric sensory, and motor functions in healthy
      volunteers.
AB  - Chloride channels modulate gastrointestinal neuromuscular functions in vitro.
      Lubiprostone, a selective type 2 chloride channel (ClC-2) activator, induces
      intestinal secretion and has been shown to relieve constipation in clinical
      trials; however, the effects of lubiprostone on gastric function and whole gut
      transit in humans are unclear. Our aim was to compare the effects of the
      selective ClC-2 activator lubiprostone on maximum tolerated volume (MTV) of a
      meal, postprandial symptoms, gastric volumes, and gastrointestinal and colonic
      transit in humans. We performed a randomized, parallel-group, double-blind,
      placebo-controlled study evaluating the effects of lubiprostone (24 microg bid)
      in 30 healthy volunteers. Validated methods were used: scintigraphic
      gastrointestinal and colonic transit, SPECT to measure gastric volumes, and the
      nutrient drink ("satiation") test to measure MTV and postprandial symptoms.
      Lubiprostone accelerated small bowel and colonic transit, increased fasting
      gastric volume, and retarded gastric emptying. MTV values were reduced compared
      with placebo; however, the MTV was within the normal range for healthy adults in
      13 of 14 participants, and there was no significant change compared with baseline
      measurements. Lubiprostone had no significant effect on postprandial gastric
      volume or aggregate symptoms but did decrease fullness 30 min after the fully
      satiating meal. Thus the ClC-2 activator lubiprostone accelerates small
      intestinal and colonic transit, which confers potential in the treatment of
      constipation.

PMID- 16603732
TI  - Identification of the MLL2 complex as a coactivator for estrogen receptor alpha.
AB  - A novel estrogen receptor (ER)alpha coactivator complex, the MLL2 complex, which
      consists of MLL2, ASH2, RBQ3, and WDR5, was identified. ERalpha directly binds to
      the MLL2 complex through two LXXLL motifs in a region of MLL2 near the C terminus
      in a ligand-dependent manner. Disrupting the interaction between ERalpha and the
      MLL2 complex with small interfering RNAs specific against MLL2 or an MLL2
      fragment representing the interacting region with ERalpha significantly inhibited
      the ERalpha transcription activity. The MLL2 complex was recruited on promoters
      of ERalpha target genes along with ERalpha upon estrogen stimulation. Inhibition
      of MLL2 expression decreased the estrogen-induced expression of ERalpha target
      genes cathepsin D and to a lesser extent pS2. In addition, MCF-7 cell growth was
      also inhibited by the depletion of MLL2. These results demonstrate that the
      ERalpha signaling pathway is critically dependent on its direct interaction with
      the MLL2 complex and suggest a central role for the MLL2 complex in the growth of
      ERalpha-positive cancer cells.

PMID- 16603731
TI  - Mild increases in portal pressure upregulate vascular endothelial growth factor
      and endothelial nitric oxide synthase in the intestinal microcirculatory bed,
      leading to a hyperdynamic state.
AB  - Increased nitric oxide (NO) is the main factor leading to the hyperdynamic
      circulation associated with advanced portal hypertension (PHT), but the initial
      mechanisms and the magnitude of increase in portal pressure required to trigger
      NO production are not known. We addressed these issues by studying systemic and
      splanchnic hemodynamics and endothelial NO synthase (eNOS) and VEGF expression in
      rats with different degrees of portal hypertension. Portal vein ligation (PVL)
      performed over needles of three different calibers (16-, 18-, and 20-gauge)
      yielded different degrees of PHT and portosystemic shunting. Compared with sham
      rats, all three groups of PVL rats exhibited features of hyperdynamic
      circulation. Rats with minimal portal hypertension (PVL with a 16-gauge needle)
      showed an early increase in VEGF and eNOS expression selectively at the jejunum.
      Immunofluorescence showed that VEGF expression was located in highly vascularized
      areas of the mucosa. Inhibition of VEGF signaling markedly attenuated the
      increase in eNOS expression. In conclusion, mild increases in portal pressure are
      enough to upregulate eNOS at the intestinal microcirculation, and this occurs, at
      least in part, through VEGF upregulation.

PMID- 16603733
TI  - Sp1 and Sp3 mediate constitutive transcription of the human hyaluronan synthase 2
      gene.
AB  - The linear glycosaminoglycan hyaluronan (HA) is synthesized at the plasma
      membrane by the HA synthase (HAS) enzymes HAS1, -2, and -3 and performs multiple
      functions as part of the vertebrate extracellular matrix. Up-regulation of HA
      synthesis in the renal corticointerstitium, and the resultant extracellular
      matrix expansion, is a common feature of renal fibrosis. However, the regulation
      of expression of these HAS isoforms at transcriptional and translational levels
      is poorly understood. We have recently described the genomic structures of the
      human HAS genes, thereby identifying putative promoter regions for each isoform.
      Further analysis of the HAS2 gene identified the transcription initiation site
      and showed that region F3, comprising the proximal 121 bp of promoter sequence,
      mediated full constitutive transcription. In the present study, we have analyzed
      this region in the human renal proximal tubular epithelial cell line HK-2.
      Electrophoretic mobility shift and promoter assay data demonstrated that
      transcription factors Sp1 and Sp3 bound to three sites immediately upstream of
      the HAS2 transcription initiation site and that mutation of the consensus
      recognition sequences within these sites ablated their transcriptional response.
      Furthermore, subsequent knockdown of Sp1 or Sp3 using small interfering RNAs
      decreased constitutive HAS2 mRNA synthesis. In contrast, significant binding of
      HK-2 nuclear proteins by putative upstream NF-Y, CCAAT, and NF-kappaB recognition
      sites was not observed. The identification of Sp1 and Sp3 as principal mediators
      of HAS2 constitutive transcription augments recent findings identifying upstream
      promoter elements and provides further insights into the mechanism of HAS2
      transcriptional activation.

PMID- 16603734
TI  - A conditional mutant deficient in hypoxanthine-guanine phosphoribosyltransferase
      and xanthine phosphoribosyltransferase validates the purine salvage pathway of
      Leishmania donovani.
AB  - Leishmania donovani cannot synthesize purines de novo and express a multiplicity
      of enzymes that enable them to salvage purines from their hosts. Previous efforts
      to generate an L. donovani strain deficient in both hypoxanthine-guanine
      phosphoribosyl-transferase (HGPRT) and xanthine phosphoribosyltransferase (XPRT)
      using gene replacement approaches were not successful, lending indirect support
      to the hypothesis that either HGPRT or XPRT is crucial for purine salvage by the
      parasite. We now report the genetic confirmation of this hypothesis through the
      construction of a conditional delta hgprt/delta xprt mutant strain that exhibits
      an absolute requirement for 2'-deoxycoformycin, an inhibitor of the leishmanial
      adenine aminohydrolase enzyme, and either adenine or adenosine as a source of
      purine. Unlike wild type parasites, the delta hgprt/delta xprt strain cannot
      proliferate indefinitely without 2'-deoxycoformycin or with hypoxanthine,
      guanine, xanthine, guanosine, inosine, or xanthosine as the sole purine nutrient.
      The delta hgprt/delta xprt mutant infects murine bone marrow-derived macrophages
      <5% as effectively as wild type parasites and cannot sustain an infection. These
      data establish genetically that either HGPRT or XPRT is absolutely essential for
      purine acquisition, parasite viability, and parasite infectivity of mouse
      macrophages, that all exogenous purines are funneled to hypoxanthine and/or
      xanthine by L. donovani, and that the purine sources within the macrophage to
      which the parasites have access are HGPRT or XPRT substrates.

PMID- 16603735
TI  - Where is the research on homeless persons and suicide?

PMID- 16603737
TI  - Law & psychiatry: Legal concerns for psychiatrists who maintain Web sites.
AB  - Courts recognize three types of Web sites: passive, which provide basic
      information; business, on which business is conducted; and intermediate, which
      are somewhat interactive but conduct no business. Inviting contact from site
      visitors may lead to inadvertent doctor-patient relationships, with ensuing legal
      duties. Statements made may be considered explicit warranties, which are subject
      to lawsuits when not fulfilled. Providing services to out-of-state clients may
      amount to practicing without a license. The author reviews Federation of State
      Medical Boards guidelines for appropriate use of the Internet in medical practice
      and offers ethical principles to help guide decisions about structure and content
      of passive sites.

PMID- 16603738
TI  - Personal accounts: Brain training: an athletic model for brain rehabilitation.

PMID- 16603739
TI  - Datapoints: Smoking and smoking cessation among persons with severe mental
      illnesses.

PMID- 16603740
TI  - Estimated payments to employment service providers for persons with mental
      illness in the Ticket to Work program.
AB  - OBJECTIVE: The Ticket to Work and Work Incentives Improvement Act of 1999 removes
      work disincentives and promotes access to vocational services for people with
      disabilities. This study calculated the amount of payments that would have been
      made to employment service providers if study participants had been enrolled in
      the Ticket program. METHODS: Data were from 450 Social Security Disability
      Insurance beneficiaries with psychiatric disabilities enrolled in a multisite
      study of supported employment. Earnings over two years were used to calculate
      provider payments under two reimbursement formulas used in the Ticket program.
      RESULTS: Only a quarter of service recipients (26 percent) reached earnings
      levels that would have triggered provider payments under the first reimbursement
      formula. Only 4 percent would have completed their trial work period and left the
      rolls, generating payments under the second formula. CONCLUSIONS: The current
      provider payment systems of the Ticket to Work program do not reflect the reality
      of rehabilitation for individuals with severe mental illness. Reforms should take
      into account outcomes of return-to-work services for this population.

PMID- 16603741
TI  - Patterns of adult psychotherapy in psychiatric practice.
AB  - OBJECTIVE: Psychotherapy has long been recognized as a key component of
      psychiatric care. However, concerns have been raised about access to
      psychotherapy as a result of changes in the financing and management of care.
      This study examined patterns and predictors of receipt of psychotherapy among
      patients of psychiatrists. METHODS: Data were collected for 587 psychiatrists who
      participated in the American Psychiatric Institute for Research and Education's
      Practice Research Network 1999 Study of Psychiatric Patients and Treatments,
      which generated nationally representative data for 1,589 adult patients. RESULTS:
      Findings indicate that more than 66 percent of patients of psychiatrists received
      some form of psychotherapy from the psychiatrist or another provider in the past
      30 days--56 percent from their psychiatrist and 10 percent from another
      clinician. Although 72 percent of patients with depression received
      psychotherapy, more than half of those with schizophrenia did not. CONCLUSIONS: A
      majority of patients of psychiatrists received psychotherapy from their
      psychiatrist. However, these rates varied by demographic, diagnostic, and health
      plan characteristics and by practice setting. Further research determining if
      these observed patterns of psychotherapy are related to differential outcomes is
      needed.

PMID- 16603742
TI  - Research on day treatment programs for preschoolers with disruptive behavior
      disorders.
AB  - OBJECTIVE: This review examined the literature on psychosocial treatments for
      preschoolers with disruptive behavior disorders to delineate ways in which
      interventions developed in research settings can be used to enhance existing
      clinical preschool day treatment programs. METHODS: A PsycINFO search was
      performed by using the keywords "day treatment," "behavior problems," "disruptive
      behavior disorder," and "oppositional defiant disorder" to find articles
      published between 1974 and 2004 on randomized controlled trials of psychosocial
      interventions for preschoolers (ages two to five years). No randomized controlled
      trials of multimodal day treatment programs were found. Therefore, studies on
      multimodal day treatment were selected on the basis of whether they presented
      quantitative outcome data. RESULTS AND CONCLUSIONS: Little research was available
      on the effectiveness of day treatment programs, despite the programs' prevalence
      as a treatment modality for disruptive preschoolers. In contrast, many
      interventions in the disruptive behavior disorder research have not made their
      way into clinical practice. Preschool day treatment programs may be enhanced by
      improving access to care, emphasizing social problem-solving skills, and using
      strategies to engage families in treatment. Research studies on existing day
      treatment programs are needed to clarify the role of these programs in child
      psychiatry clinics and to shed light on optimal methods of service delivery.

PMID- 16603743
TI  - Experiences of and attitudes toward mental health services among older youths in
      foster care.
AB  - OBJECTIVES: This study explored the experiences of youths in the Missouri foster
      care system who were receiving mental health services in order to identify
      characteristics that they valued in relationships with mental health
      professionals and in the services they received and to examine whether their
      attitudes toward services were associated with their experiences with services.
      METHODS: As part of a larger study, 389 youths aged 17 years were asked open
      ended questions about their experiences with mental health providers. The
      qualitative responses were classified through thematic analysis, and the
      frequencies of themes were assessed. Service use was measured, and the confidence
      subscale of the Attitude Toward Seeking Professional Psychological Help scale was
      used to measure attitudes. RESULTS: Youths' comments generally centered on three
      aspects of their mental health care: their relationship with their mental health
      provider, the level of professionalism of their provider, and the effects of the
      treatment, including medication management. Youths who reported only negative
      experiences had less positive attitudes toward services than other youths, but
      they were not any more likely to have experienced changes in service use or
      medication six months later. CONCLUSIONS: Soliciting feedback from youths about
      mental health services is important to the provision of high-quality care. In
      addition to themes identified in similar studies, this study suggests that
      medication management plays an important role in the acceptability of the
      treatment that youths receive.

PMID- 16603744
TI  - Involvement in the child welfare system among mothers with serious mental
      illness.
AB  - OBJECTIVE: This study sought to determine the association between maternal
      schizophrenia and major affective disorders (serious mental illness) and child
      custody arrangements in a sample of Medicaid-eligible mothers. METHODS: Medicaid
      eligibility and claims data were merged with data from the child welfare system
      in Philadelphia for 1995 to 2000. The sample comprised 4,827 female residents of
      Philadelphia between the ages of 15 and 45 as of 1996, who were initially
      eligible for Medicaid through Aid to Families With Dependent Children between
      1995 and 1996 and who had at least one family member younger than 18 years at the
      beginning of the study period. Logistic regression was used to determine
      association between maternal mental illness and involvement in the child welfare
      system. RESULTS: Among the 4,827 mothers, 7.2 percent had a serious mental
      illness and 4.4 percent had other psychiatric diagnoses. More than 14 percent of
      mothers with serious mental illness received child welfare services, compared
      with 10.8 percent of those with other psychiatric diagnoses, and 4.2 percent of
      those without a diagnosis. After the analyses adjusted for a past inpatient
      episode, race or ethnicity, and age, mothers with serious mental illness were
      almost three times as likely to have had involvement in the child welfare system
      or to have children who had an out-of-home placement. CONCLUSIONS: The results
      suggest the urgent need for increased planning and coordination between the child
      welfare and mental health systems, including provision of parenting support as
      part of mental health treatment for mothers.

PMID- 16603745
TI  - Racial and ethnic differences in the relationship between depression severity and
      functional status.
AB  - OBJECTIVE: Major depression has a negative impact on functional status and
      quality of life, but little is known about racial or ethnic differences in the
      relationship between depression and functional disability. This study compared
      the association between depression severity and functional status among three
      different racial or ethnic groups. METHODS: Data were from participants in the
      original Patient Health Questionnaire (PHQ) Primary Care Study and PHQ Obstetrics
      Gynecology Study (N=5,427). Among the study participants, 62.0 percent were non
      Hispanic white, 14.8 percent were African American, and 23.1 percent were Latino.
      Depression severity was assessed with the PHQ-9, the self-administered DSM-IV
      criteria-based depression module of the PHQ diagnostic instrument for mental
      disorders. Functional status was measured with the scales of the Medical Outcomes
      Study 20-item Short Form Health Survey (SF-20), self-reported disability days,
      clinic visits, and symptom-related difficulty. Groups were compared in terms of
      mean PHQ-9 scores and functional status at varying levels of depression severity.
      Linear regression was used to control for age, gender, education level, and
      language. RESULTS: Mean PHQ-9 scores were not significantly different between the
      three different racial or ethnic groups. Similar linear associations were found
      in all three racial or ethnic groups between increasing PHQ-9 scores (more severe
      depression) and worsening function on the SF-20 scales and an increased number of
      disability days and clinic visits. Latinos reported significantly less functional
      impairment on all measures of functionality compared with non-Hispanic whites.
      CONCLUSIONS: Functional impairment increased with increasing levels of depression
      severity in all three racial or ethnic groups, although Latinos consistently
      reported fewer functional disturbances compared with non-Hispanic whites.

PMID- 16603746
TI  - Racial and gender differences in utilization of Medicaid substance abuse services
      among adolescents.
AB  - OBJECTIVE: This study examined race and gender disparities in utilization of
      substance abuse treatment among adolescents enrolled in Medicaid in Tennessee.
      METHODS: By using Medicaid enrollment, encounter, and claims data, utilization of
      substance abuse services for the population of adolescents enrolled in TennCare
      was examined in two ways. The first utilization measure considered annual
      utilization rates and probability of use of substance abuse services for the
      statewide population of enrolled adolescents (approximately 170,000 per year).
      The second examined the age at which the first substance abuse service was
      received for the 8,473 youths who had that service paid for by TennCare during
      state fiscal years 1997 to 2001. RESULTS: Proportionally, among adolescents, more
      whites than blacks and more males than females used substance abuse services. The
      disparities were greater than differences in prevalence rates explain. Black
      females had the greatest disparity in service utilization. Whites and females
      received their first substance abuse service at a younger age than blacks or
      males in this Medicaid population. However, the age difference may not be
      clinically significant. CONCLUSIONS: The low utilization rates, in general, and
      the disparities in service use by race and gender raise questions about the
      identification of substance use problems at both provider and system levels.

PMID- 16603747
TI  - Help seeking for substance use problems in two American Indian reservation
      populations.
AB  - OBJECTIVES: This study examined the extent and types of help seeking (biomedical,
      traditional, and 12-step groups) for substance use problems in two American
      Indian reservation populations by using data from the American Indian Service
      Utilization, Psychiatric Epidemiology, Risk, and Protective Factors Project (AI
      SUPERPFP). This study also sought to understand the correlates of such help
      seeking, including measures of need, demographic characteristics, spirituality,
      and ethnic identity. METHODS: AI-SUPERPFP, completed between 1997 and 2000, was a
      cross-sectional probability sample survey. Altogether 2,825 tribal members, aged
      18 to 54 years, representing two tribal groups living on or near their home
      reservations, were randomly sampled from the tribal rolls. Response rates
      averaged 75.3 percent. The primary outcome measure was help seeking in the past
      year for substance use problems, which was further divided into help seeking from
      biomedical services, traditional healing sources, and 12-step programs. RESULTS:
      Help-seeking rates were high, with 13 percent of the population and 38 percent of
      those with diagnoses of substance use disorders in the past year having sought
      services for alcohol or drug problems in the preceding 12 months. Correlates of
      help seeking included variables related to need for services (substance use
      disorders, tobacco use, and mental and physical health problems), marital status,
      and spirituality. Slightly more than half of service users sought help from
      formal biomedical providers; use of traditional healing and 12-step programs was
      also common. Need and spirituality variables best differentiated among the users
      of the three modalities. CONCLUSIONS: Help seeking for alcohol and drug problems
      was common in these communities, with traditional healing and 12-step resources
      as essential components of the local service ecologies.

PMID- 16603748
TI  - Multiple-family group treatment for English- and Vietnamese-speaking families
      living with schizophrenia.
AB  - OBJECTIVE: This study, which was the first evaluation in Australia of multiple
      family group treatment, explored the effectiveness of this approach for a newly
      arrived non-English speaking migrant group, first-generation Vietnamese families,
      and for English-speaking families. METHODS: Thirty-four pairs of English-speaking
      consumers and family members and 25 Vietnamese-speaking pairs were randomly
      assigned to a multiple-family group or a control group. All consumers had a
      diagnosis of schizophrenia. The multiple-family group intervention (26 sessions
      over 12 months) was delivered as an adjunct to case management services, which
      all consumers received. Outcomes, which were measured immediately after treatment
      and 18 months later, included the number of relapse episodes; the presence and
      severity of symptoms, as measured by the Brief Psychiatric Rating Scale (BPRS)
      and the Scale for the Assessment of Negative Symptoms; and social functioning, as
      measured by the Family Burden Scale, the Health of the Nation Outcome Scale, and
      the Quality of Life Scale. RESULTS: Relapse rates immediately after treatment
      were significantly lower for the multiple-family group than for the control group
      (12 and 36 percent), and relapse rates were also lower during the follow-up
      period (25 and 63 percent). BPRS ratings were significantly lower for
      participants in the multiple-family group, and vocational outcomes also improved.
      The reductions in relapse and symptoms were similar for the English-speaking and
      the Vietnamese-speaking family groups; sample size precluded statistical analysis
      of differences. CONCLUSIONS: Multiple-family group treatment is an effective
      cognitive-behavioral intervention in the treatment of schizophrenia. The findings
      suggest continued application of and research on family interventions for non
      English speaking migrant populations.

PMID- 16603749
TI  - Predictors of missed first appointments at community mental health centers after
      psychiatric hospitalization.
AB  - OBJECTIVE: This study was conducted to determine the practical, readily
      accessible predictors of missed first outpatient appointments in a community
      mental health setting after psychiatric hospitalization. METHODS: Data were
      collected from treatment team members and from charts of 234 consecutively
      discharged patients from two inpatient units in a large, urban, county hospital.
      Data on whether the patient attended the first scheduled outpatient community
      mental health appointment were gathered by telephone contact with outpatient
      clinics. Outcome data were available for 221 patients. Bivariate tests examined a
      variety of demographic, psychosocial, and clinical characteristics that may be
      associated with nonadherence. Significant predictors were entered into a logistic
      regression model to determine effect estimates (adjusted odds ratios). RESULTS:
      In bivariate tests, a number of variables were predictive of nonadherence with
      the first scheduled outpatient appointment. In the logistic regression model, the
      four characteristics that were independently significant predictors included
      involuntary legal status at discharge or leaving against medical advice, not
      having an established outpatient clinician, axis IV problems related to the
      primary support group (for example, death of a family member or health problems
      in the family), and number of days from hospital discharge to the follow-up
      appointment. CONCLUSIONS: Clinical, policy, and programmatic implications may be
      elaborated by studying risk factors for nonadherence in a community mental health
      setting. Given the multitude of problems associated with nonadherence,
      interventions should be tailored around specific characteristics that elevate the
      risk of nonadherence, especially nonadherence in the form of failure to attend
      the first appointment after psychiatric hospitalization.

PMID- 16603750
TI  - Personality disorders and unmet needs among psychiatric inpatients.
AB  - OBJECTIVE: This study sought to examine the association between unmet need and
      personality disorders in a sample of psychiatric inpatients. The authors tested
      the hypothesis that the presence of a personality disorder would be independently
      associated with a significantly greater number of unmet needs. METHODS: A total
      of 153 psychiatric inpatients from four acute hospital wards serving an inner
      city borough in London, United Kingdom, received standardized assessments of need
      and personality disorder by use of the Camberwell Assessment of Need Short
      Assessment Schedule and Structured Clinical Interview for DSM-IV Personality
      Disorders. RESULTS: Fifty-four percent of the sample had a personality disorder.
      The presence of a personality disorder was associated with greater unmet need. In
      multiple regression analyses, after adjustment was made for the effects of all
      covariates, severity of personality disorder was significantly associated with
      unmet need. Personality disorder was significantly associated with greater need
      in eight of 22 domains of need: self-care, psychotic symptoms, psychological
      distress, risk to self, risk to others, alcohol use, sexual expression, and
      budgeting. CONCLUSIONS: Personality disorder was found to be independently
      associated with a greater level of unmet need among psychiatric inpatients. The
      study highlights for the first time the importance of a comprehensive assessment
      of need for patients with personality disorders.

PMID- 16603751
TI  - Use of the Sequential Intercept Model as an approach to decriminalization of
      people with serious mental illness.
AB  - The Sequential Intercept Model provides a conceptual framework for communities to
      use when considering the interface between the criminal justice and mental health
      systems as they address concerns about criminalization of people with mental
      illness. The model envisions a series of points of interception at which an
      intervention can be made to prevent individuals from entering or penetrating
      deeper into the criminal justice system. Ideally, most people will be intercepted
      at early points, with decreasing numbers at each subsequent point. The
      interception points are law enforcement and emergency services; initial detention
      and initial hearings; jail, courts, forensic evaluations, and forensic
      commitments; reentry from jails, state prisons, and forensic hospitalization; and
      community corrections and community support. The model provides an organizing
      tool for a discussion of diversion and linkage alternatives and for
      systematically addressing criminalization. Using the model, a community can
      develop targeted strategies that evolve over time to increase diversion of people
      with mental illness from the criminal justice system and to link them with
      community treatment.

PMID- 16603752
TI  - Introduction: Report of the APA's task force on research ethics.

PMID- 16603753
TI  - Ethical principles and practices for research involving human participants with
      mental illness.
AB  - This report of the American Psychiatric Association's task force on research
      ethics addresses ethical issues related to the conduct of research involving
      human participants with mental illness. The report includes discussion of
      recruitment and ongoing participation of persons whose decisional capacity may be
      impaired and the ethical costs of categorically excluding persons with serious
      mental illness. Investigators should receive education in research ethics that
      addresses rules and norms governing research; sensitivity to ethical implications
      of decisions and actions; and skills in ethical problem solving, including
      ascertainment and disclosure of conflicts of interest. Ethical research design
      must ensure that a study has scientific merit, methods used should yield
      knowledge of value, and procedures must minimize risks to participants and
      optimize benefits. When risks are anticipated, plans should be developed to
      ensure participants' safety. The task force concludes with 12 recommendations for
      researchers, ethical review bodies, and advocacy groups to promote research and
      ensure ethical conduct of research.

PMID- 16603754
TI  - Surviving the tornado of mental illness: psychiatric survivors' experiences of
      getting, losing, and keeping housing.
AB  - This qualitative study explored experiences of psychiatric consumer-survivors
      related to housing. Nine focus groups involving 90 people were conducted in urban
      and rural areas in South-Western Ontario. A set of open-ended questions was used.
      Many participants described a devastating experience of losing much of what was
      important to them and going through a long arduous process to rebuild their
      lives. Group discussions were audiotaped and transcribed. Individual and team
      analyses of the transcripts revealed that psychiatric survivors experienced three
      levels of upheaval, loss, and destruction, similar to the effects of a tornado:
      losing ground, struggling to survive, and gaining stability. Within each of these
      levels, five major themes were identified: living in fear, losing control of
      basic human rights, attempting to hold onto and create relationships, identifying
      supports and seeking services, and obtaining personal space and place. A caring
      community response, including adequate housing, income support, and community
      care, can help people rebuild their lives.

PMID- 16603755
TI  - Use of emergency department services for somatic reasons by people with serious
      mental illness.
AB  - OBJECTIVE: This study identified factors associated with use of the emergency
      department for medical reasons among individuals with serious mental illness.
      METHODS: A total of 200 randomly selected outpatients who were receiving
      community-based psychiatric care were recruited for the study and interviewed
      with items from the National Health Interview Survey and other national health
      surveys. RESULTS: Emergency department use (37 percent of the sample) was
      negatively associated with older age and positively associated with the number of
      co-occurring medical conditions, smoking, recent injury, and recent change in
      health care provider. CONCLUSIONS: The relatively high rate of emergency
      department use may be suggestive of inappropriate use or may reflect perceived
      barriers to care. Future work should identify specific reasons for seeking care
      in the emergency department and develop interventions to optimize appropriate
      emergency department use.

PMID- 16603756
TI  - Mental health services for homebound elders from home health nursing agencies and
      home care agencies.
AB  - OBJECTIVE: This study examined the practices of home care agencies and home
      health nursing agencies in the management and treatment of homebound clients with
      behavioral problems, dementia, and undiagnosed mental illnesses. METHODS: A
      survey was mailed to all 54 directors of agencies in Rhode Island in 2003; 53
      responded, either by mail or telephone. RESULTS: Data indicated a lack of
      psychiatric services, a reluctance to address behavioral problems, and a failure
      to identify undiagnosed disorders. There was also a bias against accepting
      individuals with primary psychiatric disorders. CONCLUSIONS: Although the
      population of homebound elders with mental illness is increasing, their needs are
      not being met by these agencies.

PMID- 16603757
TI  - Hepatitis C treatment eligibility and outcomes among patients with psychiatric
      illness.
AB  - OBJECTIVE: This study characterized the utilization and outcomes of hepatitis C
      virus (HCV) treatment among patients with psychiatric illness. METHODS: HCV
      treatment evaluations were tracked among 360 patients with HCV infection and
      psychiatric illness (substance use disorders, anxiety disorders, affective
      disorders, or psychotic disorders). RESULTS: Two-thirds of patients did not
      receive HCV treatment, 11 percent of patients died during the study period, and
      42 percent were excluded from HCV treatment because of nonadherence to the
      evaluation process or diagnoses of psychiatric and substance use disorders.
      Interferon-alpha and ribavirin treatment resulted in viral clearance in 10
      percent of patients. CONCLUSIONS: A majority of patients with HCV and psychiatric
      illness did not receive HCV treatment, and HCV infection was associated with
      significant mortality. Study results highlight the need to develop innovative
      approaches to engage such patients in HCV treatment and to successfully manage
      psychiatric illness during HCV treatment.

PMID- 16603758
TI  - Knowledge of grocery shopping skills as a mediator of cognition and performance.
AB  - OBJECTIVE: Cognitive impairments in serious mental illness are associated with
      poorer community outcomes; yet the mechanisms through which cognition limits
      functioning are unknown. This study examined knowledge of grocery shopping skills
      as a mediator of cognition and performance of grocery shopping skills. METHODS:
      Fifty-one individuals with serious mental illness were administered measures of
      cognition, as well as measures of knowledge and performance of grocery shopping
      skills. RESULTS: When knowledge of grocery shopping skills was introduced as a
      mechanism through which cognition influences performance, almost perfect
      mediation was achieved (slope of the regression dropped from B=.32 to B=.03).
      CONCLUSIONS: The search for mediators can improve our understanding of how
      cognition influences community functioning.

PMID- 16603760
TI  - Elimination of seclusion and restraint: a reasonable goal?

PMID- 16603762
TI  - Clinical case management, case management, and ACT.

PMID- 16603765
TI  - Clinical case management, case management, and ACT.

PMID- 16603766
TI  - Assessment and treatment of Iraqi prisoners and civilians.

PMID- 16603767
TI  - Assessment and treatment of Iraqi prisoners and civilians.

PMID- 16603769
TI  - The FATC domains of PIKK proteins are functionally equivalent and participate in
      the Tip60-dependent activation of DNA-PKcs and ATM.
AB  - Members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family,
      including the ATM, DNA-PKcs, Atr, and Trrap proteins, function in signal
      transduction pathways that activate the DNA damage response. PIKK proteins
      contain a conserved C-terminal FAT/kinase domain/FATC domain structure. The FATC
      domain of ATM mediates the interaction between ATM and Tip60, a histone
      acetyltransferase that regulates activation of ATM. Here, we examined whether the
      FATC domains of DNA-PKcs, Atr, and Trrap were also able to interact with Tip60.
      Deletion of the FATC domain of ATM blocked the interaction between ATM and Tip60
      and suppressed the activation of ATM kinase activity by DNA damage. Replacement
      of the FATC domain of ATM with the FATC domains of DNA-PKcs, Atr, or Trrap
      restored the activation of ATM and its association with Tip60. These results
      indicate that the FATC domains of DNA-PKcs, Atr, Trrap, and ATM are functionally
      equivalent. Immunoprecipitation experiments demonstrated that Tip60 is
      constitutively associated with DNA-PKcs and that the histone acetyltransferase
      activity associated with DNA-PKcs is up-regulated by DNA damage. When Tip60
      expression was suppressed by small interfering RNA, the activation of DNA-PKcs
      (measured by autophosphorylation of DNA-PKcs at serine 2056 and threonine 2609)
      was inhibited, demonstrating a key role for Tip60 in the activation of DNA-PKcs
      by DNA damage. The conserved FATC domain of PIKK proteins may therefore function
      as a binding domain for the Tip60 histone acetyltransferase. Further, the ability
      of Tip60 to regulate the activation of both ATM and DNA-PKcs in response to DNA
      damage demonstrates that Tip60 is a key component of the DNA damage-signaling
      network.

PMID- 16603770
TI  - A high mobility group protein binds to long CAG repeat tracts and establishes
      their chromatin organization in Saccharomyces cerevisiae.
AB  - Long CAG repeat tracts cause human hereditary neurodegenerative diseases and have
      a propensity to expand during parental passage. Unusual physical properties of
      CAG repeat tracts are thought to contribute to their instability. We investigated
      whether their unusual properties alter the organization of CAG repeat tract
      chromatin. We report that CAG repeat tracts, embedded in yeast chromosomes, have
      a noncanonical chromatin organization. Digestion of chromatin with the
      restriction enzyme Fnu4HI reveals hypersensitive sites occurring approximately
      125 bp apart in the repeat tract. To determine whether a non-histone protein
      establishes this pattern, we performed a yeast one-hybrid screen using CAG repeat
      tracts embedded in front of two reporter genes. The screen identified the high
      mobility group box protein Hmo1. Chromatin immunoprecipitation of epitope-tagged
      Hmo1 selectively precipitates CAG repeat tracts DNAs that range from 26 to 126
      repeat units. Moreover, deletion of HMO1 drastically alters the Fnu4HI digestion
      pattern of CAG repeat chromatin. These results show that Hmo1 binds to CAG repeat
      tracts in vivo and establish the basis of their novel chromatin organization.

PMID- 16603771
TI  - The WSTF-SNF2h chromatin remodeling complex interacts with several nuclear
      proteins in transcription.
AB  - The WSTF (Williams syndrome transcription factor) protein is involved in vitamin
      D-mediated transcription and replication as a component of two distinct ATP
      dependent chromatin remodeling complexes, WINAC and WICH, respectively. We show
      here that the WICH complex (WSTF-SNF2h) interacts with several nuclear proteins
      as follows: Sf3b155/SAP155, RNA helicase II/Gualpha, Myb-binding protein 1a, CSB,
      the proto-oncogene Dek, and nuclear myosin 1 in a large 3-MDa assembly, B-WICH,
      during active transcription. B-WICH also contains RNAs, 45 S rRNA, 5 S rRNA, 7SL
      RNA, and traces of the U2 small nuclear RNA. The core proteins, WSTF, SNF2h, and
      nuclear myosin 1, are associated with the RNA polymerase III genes 5 S rRNA genes
      and 7SL, and post-transcriptional silencing of WSTF reduces the levels of these
      transcripts. Our results show that a WSTF-SNF2h assembly is involved in RNA
      polymerase III transcription, and we suggest that WSTF-SNF2h-NM1 forms a platform
      in transcription while providing chromatin remodeling.

PMID- 16603772
TI  - Iron-sulfur cluster biosynthesis: characterization of Escherichia coli CYaY as an
      iron donor for the assembly of [2Fe-2S] clusters in the scaffold IscU.
AB  - The biogenesis of iron-sulfur [Fe-S] clusters requires the coordinated delivery
      of both iron and sulfide. Sulfide is provided by cysteine desulfurases that use L
      cysteine as sulfur source. So far, the physiological iron donor has not been
      clearly identified. CyaY, the bacterial ortholog of frataxin, an iron binding
      protein thought to be involved in iron-sulfur cluster formation in eukaryotes, is
      a good candidate because it was shown to bind iron. Nevertheless, no functional
      in vitro studies showing an involvement of CyaY in [Fe-S] cluster biosynthesis
      have been reported so far. In this paper we demonstrate for the first time a
      specific interaction between CyaY and IscS, a cysteine desulfurase participating
      in iron-sulfur cluster assembly. Analysis of the iron-loaded CyaY protein
      demonstrated a strong binding of Fe(3+) and a weak binding of Fe(2+) by CyaY.
      Biochemical analysis showed that the CyaY-Fe(3+) protein corresponds to a mixture
      of monomer, intermediate forms (dimer-pentamers), and oligomers with the
      intermediate one corresponding to the only stable and soluble iron-containing
      form of CyaY. Using spectroscopic methods, this form was further demonstrated to
      be functional in vitro as an iron donor during [Fe-S] cluster assembly on the
      scaffold protein IscU in the presence of IscS and cysteine. All of these results
      point toward a link between CyaY and [Fe-S] cluster biosynthesis, and a possible
      mechanism for the process is discussed.

PMID- 16603773
TI  - Episiotomy--should we continue it as routine practice.

PMID- 16603774
TI  - The practice of episiotomy in public hospitals in Hong Kong.
AB  - OBJECTIVE: To review the use of episiotomy during vaginal delivery in Hong Kong
      public hospitals. DESIGN: Prospective observational survey. SETTING: Public
      hospitals, Hong Kong. PARTICIPANTS: Women who underwent normal vaginal delivery
      of a singleton foetus with cephalic presentation. MAIN OUTCOME MEASURES: Number
      of women having an episiotomy, severe-degree (third- or fourth-degree) tear,
      other types of tear, blood loss at delivery, postpartum haemorrhage, need for
      blood transfusion, puerperal pyrexia, wound infection, gaping wound that required
      suture removal, and drainage or resuturing of a perineal wound. RESULTS: Between
      1 January and 31 March 2003, there were 6222 singleton spontaneous normal vaginal
      deliveries in the public hospitals of Hong Kong. Of the 6167 women in whom the
      status of the perineum was known, episiotomy was performed in 5274 (85.5%).
      Primiparous women were more likely to undergo episiotomy at delivery than
      multiparous women (97.9% vs 71.4%). Women with episiotomy had significantly less
      perineal tearing of any kind than those without. The occurrence of any type of
      perineal tear and severe-degree (third- or fourth-degree) tear was significantly
      lower in primiparous women who had an episiotomy than those without (P<0.05).
      Women with episiotomy had increased mean blood loss at delivery but other
      complications were not significantly increased. CONCLUSIONS: In Hong Kong,
      episiotomy is routinely performed during normal vaginal delivery. It is
      associated with a significantly lower overall rate of perineal tearing. This
      study was observational, nonetheless the occurrence of other complications was
      likely to increase when episiotomy was performed. Firm evidence from several
      randomised controlled studies shows that routine episiotomy is unjustified and
      possibly harmful. Routine episiotomy should not be promoted in Hong Kong without
      further randomised controlled study.

PMID- 16603775
TI  - BiliCheck transcutaneous bilirubinometer: a screening tool for neonatal jaundice
      in the Chinese population.
AB  - OBJECTIVE: To verify the usefulness of the BiliCheck transcutaneous bilirubin
      meter as a screening device for neonatal jaundice in a Chinese population
      compared with the Minolta bilirubin meter. DESIGN: A prospective correlation
      study that compared transcutaneous bilirubin measurements with serum bilirubin
      levels. SETTING: Obstetric ward and a neonatal unit of a regional hospital in
      Hong Kong. PATIENTS: Neonates with gestation above 32 weeks with neonatal
      jaundice who were admitted between April 2001 and February 2002. MAIN OUTCOME
      MEASURES: Transcutaneous measurements of serum bilirubin obtained from the
      forehead and the sternum with two instruments: BiliCheck and Minolta Airshields
      JM 102. RESULTS: A total of 77 term and six near-term babies (gestation, 32-37
      weeks) were recruited. The mean age at the time of data collection was 3.96 days
      (range, 2-9 days). The correlations between serum bilirubin and transcutaneous
      bilirubin measurements of the two devices at the two sites were high, with a
      coefficient of 0.718 (95% confidence interval, 0.610-0.800; n=100) for forehead
      measurements, and 0.814 (95% confidence interval, 0.740-0.870; n=99) for sternum
      using the Minolta Airshields JM 102; and a coefficient of 0.757 (95% confidence
      interval, 0.657-0.827; n=98) for forehead measurements, and 0.794 (95% confidence
      interval, 0.700-0.862; n=92) for sternum using the BiliCheck. For BiliCheck, a
      cut-off point of 250 micromol/L at the forehead and 260 micromol/L at the sternum
      had a specificity of 61.9% and 70.0%, respectively with a sensitivity of 100% for
      the detection of serum bilirubin concentrations of 250 micromol/L or higher. This
      level is commonly used as the level for initiation of treatment such as
      phototherapy. CONCLUSION: BiliCheck is a useful screening tool for neonatal
      jaundice in the Chinese population and is comparable with the Minolta Airshields
      JM 102.

PMID- 16603776
TI  - Intrarectal administration of lidocaine gel versus plain lubricant gel for pain
      control during transrectal ultrasound-guided extensive 10-core prostate biopsy in
      Hong Kong Chinese population: prospective double-blind randomised controlled
      trial.
AB  - OBJECTIVE: To compare the level of pain experienced by patients during
      transrectal ultrasound-guided prostatic biopsy using intrarectal 2% lidocaine gel
      versus plain lubricant gel. DESIGN: Prospective double-blind randomised
      controlled trial. SETTING: Regional hospital, Hong Kong. PATIENTS: From March
      2002 to December 2003, patients who underwent ultrasound-guided prostate biopsy
      at a Geriatric Urology Centre. MAIN OUTCOME MEASURES: Pain and discomfort scores
      measured by horizontal visual analogue scales. RESULTS: A total of 338
      consecutive patients were randomised to lidocaine gel or plain lubricant gel
      groups. The two groups were statistically similar in demographic and disease
      characteristics. There were no significant statistical differences in pain or
      discomfort score in the lidocaine gel and plain lubricant groups--pain score:
      1.75 versus 1.79 (P=0.66) on day 0 and 0.21 versus 0.15 (P=0.97) on day 1;
      discomfort score: 0.79 versus 0.77 (P=0.86) on day 0 and 0.12 versus 0.12
      (P=0.76) on day 1. No major complications were recorded in this cohort.
      CONCLUSIONS: Transrectal ultrasound-guided trucut biopsy of the prostate can be
      safely performed with no anaesthesia in Chinese patients. Pain and discomfort are
      minimal. It was found that 2% lidocaine gel has no statistical therapeutic or
      analgesic benefit over plain lubricant gel.

PMID- 16603777
TI  - Feasibility of transradial coronary angiography and angioplasty in Chinese
      patients.
AB  - OBJECTIVE: To assess the clinical applicability, efficacy, and safety of coronary
      angiography and angioplasty via a transradial approach in local Chinese patients.
      DESIGN: Prospective case series. SETTING: Regional hospital, Hong Kong. PATIENTS:
      All patients undergoing coronary angiography and coronary angioplasty between 1
      January and 30 June 2004. INTERVENTIONS: Transradial coronary angiography and
      coronary angioplasty. MAIN OUTCOME MEASURES: Feasibility, success rate, and
      complications. RESULTS: A total of 268 coronary angiographies (62% of all
      coronary angiographies) and 118 coronary angioplasties (48% of all coronary
      angioplasties) were performed via a transradial approach. The procedural success
      rate for coronary angiography was 93.7% with a mean duration of 21.8 (standard
      deviation, 13.5) minutes compared with 17.9 (10.0) minutes for angiography via a
      femoral approach. Most (99%) patients were free from any complications. Of those
      patients who underwent elective transradial coronary angiography in the morning,
      64% were discharged on the same day. Comparison of data in the first half of the
      study period with those in the second half revealed a significant increase in the
      percentage of coronary angiographies performed via a transradial approach (from
      52% to 73%, P<0.0001), and an improved procedural success rate (from 91.5% to
      95.3%, P=0.1). For transradial coronary angioplasty, the procedural success rate
      was 98%. A total of 246 lesions (2.08 lesions per patient) were treated with no
      procedure-related complications. CONCLUSIONS: Transradial coronary angiography
      and angioplasty are feasible in a significant proportion of local Chinese
      patients and achieve a high success rate and low complication rate. It tends to
      prolong procedural duration, but improves patients' comfort and permits earlier
      ambulation and discharge. The procedural success rate improves with accumulating
      experience.

PMID- 16603778
TI  - Management of hypertension by private doctors in Hong Kong.
AB  - OBJECTIVE: To investigate the management of hypertension by private doctors in
      Hong Kong. DESIGN: Self-administered questionnaire survey. SETTING: Hong Kong.
      PARTICIPANTS: Private doctors from all districts in Hong Kong selected by simple
      random sampling from the website of "The Hong Kong Doctors Homepage" from March
      to June 2005. MAIN OUTCOME MEASURES: Practice of blood pressure measurement and
      the treatment prescribed to hypertensive patients. RESULTS: A total of 225 (46%)
      completed questionnaires were analysed. Only 24.4% of the respondents measured
      blood pressure in all new patients aged above 18 years. A total of 28.0% of
      doctors reported that hypertensive status was unknown in over 30% of their
      patients prior to their first clinic visit when it was consequently diagnosed.
      Calcium channel blockers (31%), angiotensin-converting enzyme inhibitors (28.5%),
      diuretics (27.5%), and beta-blockers (21.2%) were the most commonly prescribed
      antihypertensive medication. Drug efficacy was the reason cited by more than half
      (56.9%) of doctors for selecting a given drug. Public education about
      hypertension was considered insufficient by 66.2% of doctors and 32% believed
      that self-medication would have a very significant effect on drug compliance.
      CONCLUSIONS: In private clinics, blood pressure measurement should become a
      routine procedure. There is a need to raise public awareness of hypertension.

PMID- 16603779
TI  - Infectious diseases in children admitted from a residential child care centre.
AB  - OBJECTIVES: To describe the pattern of infectious diseases among children
      admitted from a residential child care centre and to identify any unusual
      clusters of admissions. DESIGN: Retrospective case review. SETTING: Regional
      hospital, Hong Kong. PATIENTS: All children from a residential child care centre
      aged over 28 days who were admitted from the Accident and Emergency Department to
      paediatric wards for infections from 1 January 1999 to 31 December 2003. MAIN
      OUTCOME MEASURES: Demographic data, clinical diagnoses, infectious diseases
      identified, and incidence and seasonal pattern of various infections. RESULTS: Of
      267 children admitted to the hospital over the 5-year period, 221 had infectious
      diseases. Respiratory tract infections, viral exanthema, and gastroenteritis were
      present in 83.7%, 7.2%, and 5.9%, respectively. Among those with a respiratory
      tract infection, 22.7%, 9.2%, and 8.6% had respiratory syncytial virus,
      parainfluenza virus, and influenza A or B viruses, respectively. Two unusual
      clusters of respiratory syncytial virus and parainfluenza virus were recognised
      in late 2003. CONCLUSION: Children in this residential child care centre were at
      risk of infectious diseases. Respiratory tract infection is the most common
      infectious disease in this centre. An outbreak of respiratory tract infection was
      recognised. Further efforts may be necessary to improve infection control
      measures in this setting.

PMID- 16603780
TI  - Clinical experience of trainee anaesthesiologists: logbook analysis.
AB  - OBJECTIVE: To study the clinical experience acquired by trainee
      anaesthesiologists after 6 years of training in Hong Kong. DESIGN: Retrospective
      observational study. SETTING: Recognised anaesthesiology training posts in the
      Hong Kong Hospital Authority. PARTICIPANTS: All anaesthesiology trainees who sat
      the Exit Assessment between January 2001 and June 2002 after completing more than
      48 months of anaesthetic training. MAIN OUTCOME MEASURES: Anaesthetic experience
      of trainees. RESULTS: All data provided by 25 trainees were computed for
      analysis. Each trainee administered a mean of 2668 anaesthetics over a 6-year
      period, including 57 anaesthetics for thoracic surgery, 15 for cardiac surgery,
      213 for caesarian section (34% under general anaesthesia), and 100 for
      neurosurgical operations. The paediatric anaesthesia exposure involved a mean of
      12 neonates and 180 children who were younger than 4 years. Apart from cardiac
      and thoracic anaesthesia, there was no statistical difference in subspecialty
      anaesthetic experience among trainees from different parent hospitals.
      CONCLUSION: The current training system provides sufficient anaesthetic
      experience in terms of case variety and subspecialty case numbers. There was
      uneven exposure to cardiac, thoracic, and paediatric anaesthesia. An accurate
      logbook that is reviewed regularly by a supervisor will help ensure adequate
      subspecialty exposure. An electronic logbook will facilitate a more comprehensive
      reviewing process.

PMID- 16603781
TI  - Twenty years of clinical human immunodeficiency virus (HIV) and acquired
      immunodeficiency syndrome (AIDS) in Hong Kong.
AB  - OBJECTIVE: To elucidate the development of human immunodeficiency virus (HIV)
      clinical care and research in Hong Kong. DATA SOURCES: Articles on clinical HIV
      and acquired immunodeficiency syndrome (AIDS) published from 1985 to 2004 were
      identified through four sources: Red Ribbon Centre, Special Preventive Programme,
      Secretariat of the Scientific Committee on AIDS, and PubMed search. The first
      three are operated by the Centre for Health Protection, Department of Health,
      Hong Kong. STUDY SELECTION: Key words for the literature search were 'AIDS',
      'HIV', and 'Hong Kong'. DATA EXTRACTION: Only papers with original local data
      were included. DATA SYNTHESIS: Sixty papers were identified. The contents were
      catalogued under seven areas: clinical epidemiology, HIV disease course and
      presentation, specific complications or organ-based manifestations, immunological
      evaluation and other monitoring, antiretroviral therapy, HIV/AIDS mortality, and
      HIV in specific groups. Prevalence of HIV has remained low in Hong Kong but new
      infections continue to occur together with a significant number of late
      presenters. Three published AIDS patients' series, up to the first 200 reported
      cases, identified Pneumocystis carinii pneumonia as the most common AIDS-defining
      illness in Hong Kong. Penicillium marneffei and Mycobacterium tuberculosis were
      two important specific infections studied most; uniqueness of the former in
      patients of South-East Asia was evident. Local studies of Kaposi's sarcoma and
      HIV-associated lymphoma have also been reported. Research on CD4 counts has
      revealed that it is lower in healthy and HIV-infected Chinese than their western
      counterparts. Children, pregnant women, and haemophiliac patients infected with
      HIV are among the specific groups of patients studied. Survival of patients with
      advanced disease has greatly improved over the years, particularly after the
      advent of highly active antiretroviral therapy. CONCLUSION: The clinical
      presentation and outcome of HIV/AIDS patients in Hong Kong are a mixture of those
      of western and developing countries. Research on clinical HIV/AIDS in Hong Kong
      is not only beneficial to the planning of patient care, but also enables the
      formulation of treatment guidelines and provides a reference for other countries.

PMID- 16603782
TI  - Optimising antimicrobial prescription in hospitals by introducing an
      antimicrobial stewardship programme in Hong Kong: consensus statement.
AB  - OBJECTIVE: To discuss the implementation of an 'antimicrobial stewardship
      programme' as a means to improve the quality of antimicrobial use in a hospital
      setting in Hong Kong. PARTICIPANTS: Consensus working group on 'antimicrobial
      stewardship programme', The Scientific Committee on Infection Control, Centre for
      Health Protection, Department of Health, comprised 11 experts. The remit of the
      working group was to discuss the rationale and requirement for optimising
      antimicrobial prescriptions in hospitals by the introduction of an 'antimicrobial
      stewardship programme'. EVIDENCE: PubMed articles, national and international
      guidelines, and abstracts of international meetings published between January
      2000 and December 2004 on programmes for improving the use of antimicrobials in
      hospitals. Only English medical literature was reviewed. CONSENSUS PROCESS: Data
      search was performed independently by three members of the working group. They
      met on three occasions before the meeting to discuss all collected articles. A
      final draft was circulated to the working group before a meeting on 3 January
      2005. Five commonly asked questions about an 'antimicrobial stewardship
      programme' were selected for discussion by the participants. Published
      information on the rationale, components, outcome measures, advantages, and
      disadvantages of the programme was reviewed. Recent unpublished data from local
      studies of an 'antimicrobial stewardship programme' were also discussed. The
      timing, potential problems, and practical issues involved in the implementation
      of an 'antimicrobial stewardship programme' in Hong Kong were then considered.
      The consensus statement was circulated to and approved by all participants.
      CONCLUSION: The continuous indiscriminate and excessive use of antimicrobial
      agents promotes the emergence of antibiotic-resistant organisms. Antimicrobial
      resistance substantially raises already-rising health care costs and increases
      patient morbidity and mortality. Pattern of prescriptions in hospitals can be
      improved through the implementation of an 'antimicrobial stewardship programme'.
      A 'universal' and 'continuous' 'antimicrobial stewardship programme' should now
      be established in Hong Kong hospitals.

PMID- 16603783
TI  - Acute massive haemolysis in children with glucose-6-phosphate dehydrogenase
      deficiency.
AB  - We report seven consecutive episodes of acute massive haemolysis accompanied by
      symptomatic anaemia and gross haemoglobinuria in six boys with glucose-6
      phosphate dehydrogenase deficiency seen in a regional hospital during a 12-year
      period. They presented at a mean age of 5.5 years (range, 1.5-11.3 years) with
      trough haemoglobin levels between 35 and 84 g/L. Two children developed transient
      renal impairment. Five children required erythrocyte transfusion, of whom one
      underwent exchange transfusion during the oliguric phase. Three patients required
      intensive care but all recovered from the haemolysis. The probable precipitating
      factors included consumption of fava beans (n=2), exposure to mothballs (n=1),
      treatment with herbal medicine or intramuscular injection of unknown nature
      (n=3), and upper respiratory tract infection (n=1). Although uncommon, acute
      massive haemolysis remains a life-threatening complication in children with
      glucose-6-phosphate dehydrogenase deficiency. Improvement in patient education
      and public health measures is suggested.

PMID- 16603784
TI  - Spontaneous pneumomediastinum in a scuba diver.
AB  - Pneumomediastinum usually occurs following an airleak from the lungs, or from a
      perforated oesophagus. We report on a 30-year-old man who developed
      pneumomediastinum after scuba diving. The patient presented with acute onset of
      throat pain, odynophagia, and hoarseness of voice. The literature is reviewed for
      this condition.

PMID- 16603785
TI  - Wilson's disease: a patient undiagnosed for 18 years.
AB  - Wilson's disease, an autosomal recessive disorder of copper metabolism, is the
      most common inherited hepatic disease in Hong Kong. Diagnosis is based on the
      presence of Kayser-Fleischer rings, typical neurological symptoms, and/or a low
      serum ceruloplasmin concentration (<0.20 g/L). Early detection and treatment
      protect patients and their presymptomatic siblings from devastating organ damage.
      The diagnosis of Wilson's disease may nonetheless be overlooked if only
      established clinical and laboratory tests are used as diagnostic criteria. We
      report diagnosis of the disorder using genetic analysis of ATP7B in a
      presymptomatic sibling who escaped diagnosis during family screening 18 years
      previously. The patient was 11 months old when family screening was performed
      following diagnosis of Wilson's disease in an elder sister. The boy was
      considered to be unaffected on the basis of laboratory results in the expected
      range: serum copper level, 4.6 micromol/L; serum ceruloplasmin level, 0.16 g/L;
      and 24-hour urinary copper excretion, 0.14 micromol/day. Molecular analysis of
      ATP7B was performed; it revealed that the two siblings shared the same compound
      heterozygous mutations (G943D and 2299delC). We recommend that molecular
      diagnosis is the only definitive means of diagnosing Wilson's disease in children
      younger than 1 year.

PMID- 16603786
TI  - Elephantiasic thyroid dermopathy.

PMID- 16603787
TI  - The new cardiovascular continuum.

PMID- 16603788
TI  - Doctors practising alternative medicine--the legal considerations.

PMID- 16603789
TI  - A new approach to Parkinson's disease combining caffeine, methylphenidate, and
      anticholinergic agents: case histories, pharmacological data, and a conceptual
      framework from traditional Chinese medicine.

PMID- 16603790
TI  - Copper homeostasis in the CNS: a novel link between the NMDA receptor and copper
      homeostasis in the hippocampus.
AB  - Copper is an essential nutrient that plays a fundamental role in the biochemistry
      of the central nervous system, as evidenced by patients with Menkes disease, a
      fatal neurodegenerative disorder of childhood resulting from the loss-of-function
      of a copper-transporting P-type adenosine triphosphatase (ATPase). Despite
      clinical and experimental data indicating a role for copper in brain function,
      the mechanisms and timing of the critical events affected by copper remain poorly
      understood. A novel role for the Menkes ATPase has been identified in the
      availability of an N-methyl-D-aspartate (NMDA) receptor-dependent, releasable
      pool of copper in hippocampal neurons, suggesting a unique mechanism linking
      copper homeostasis and neuronal activation within the central nervous system.
      This article explores the evidence that copper acts as a modulator of neuronal
      transmission, and that the release of endogenous copper from neurons may regulate
      NMDA receptor activity. The relationship between impaired copper homeostasis and
      neuropathophysiology suggests that impairment of copper efflux could alter
      neuronal function and thus contribute to rapid neuronal degeneration.

PMID- 16603791
TI  - Targeting myelin to optimize plasticity of spared spinal axons.
AB  - Functional re-innervation of target neurons following neurological damage such as
      spinal cord injury is an essential requirement of potential therapies. There are
      at least two avenues by which this can be achieved: (a) through the regeneration
      of injured axons and (b) through promoting plasticity of those spared by the
      initial insult. There are several reasons why the latter approach may be more
      feasible, not the least of which are the inhibitory character of the glial scar,
      the often long distances over which injured axons must regrow, and the fact that
      spared axons are often already in the vicinity of denervated targets. The
      challenge is to unveil the well-recognized intrinsic plasticity of spared axons
      in a way that avoids complications, such as pain or autonomic dysfunction. One
      approach that we as well as others have taken is to target growth-suppressing
      signaling pathways initiated in spared axons by myelin-derived proteins. This
      article reviews models used for the study of spinal axon plasticity and describes
      the anatomical and behavioral effects of interfering with myelinderived proteins,
      their receptors, and components of their intracellular signaling cascades.

PMID- 16603792
TI  - Mitochondrial involvement in amyotrophic lateral sclerosis: trigger or target?
AB  - Despite numerous reports demonstrating mitochondrial abnormalities associated
      with amyotrophic lateral sclerosis (ALS), the role of mitochondrial dysfunction
      in the disease onset and progression remains unknown. The intrinsic mitochondrial
      apoptotic program is activated in the central nervous system of mouse models of
      ALS harboring mutant superoxide dismutase 1 protein. This is associated with the
      release of cytochrome-c from the mitochondrial intermembrane space and
      mitochondrial swelling. However, it is unclear if the observed mitochondrial
      changes are caused by the decreasing cellular viability or if these changes
      precede and actually trigger apoptosis. This article discusses the current
      evidence for mitochondrial involvement in familial and sporadic ALS and concludes
      that mitochondria is likely to be both a trigger and a target in ALS and that
      their demise is a critical step in the motor neuron death.

PMID- 16603795
TI  - An improved method of left ventricular catheterization in rats.
AB  - Left ventricular catheterization is a key step for hemodynamic studies. At
      present, the right common carotid artery is a popular entrance, but right common
      carotid artery punctuation and ligation primarily leads to obstruction and second
      left ventricular catheterization in the same animal cannot be performed. In this
      note, we will describe an improved method of catheterization in rats using guide
      wires of percutaneous transluminal coronary angioplasty (PTCA) through the right
      external carotid artery and right common carotid artery, respectively. 30 rats
      anesthetized with sodium pentobarbital (50 mg kg(-1)) underwent the first
      operation and, 2 weeks later, 29 were successfully catheterized again. One rat
      died of left ventricle perforation while the hemodynamic monitor was performing.
      Therefore, our method proves able to be performed two times in one animal.
      Moreover, it inflicts less injury during the operation, because the tube was
      advanced through a soft guide wire.

PMID- 16603793
TI  - Homeostatic regulation of glutamate release in response to depolarization.
AB  - Proper nervous system function requires a balance between excitation and
      inhibition. Systems of homeostasis may have evolved in neurons to help maintain
      or restore balance between excitation and inhibition, presumably because
      excessive excitation can cause dysfunction and cell death. This article reviews
      evidence for homeostatic mechanisms within the hippocampus that lead to
      differential regulation of glutamate and gamma-aminobutyric acid release in
      response to conditions of excess depolarization. We recently found differential
      effects on glutamate release at the level of action potential coupling to
      transmitter release, vesicular release probability, and vesicle availability.
      Such differential regulation may help to prevent excitotoxicity and runaway
      excitation.

PMID- 16603796
TI  - The increase of breath ammonia induced by niacin ingestion quantified by selected
      ion flow tube mass spectrometry.
AB  - The ingestion of relatively large doses of the vitamin niacin by healthy
      volunteers results in a reddening of the skin, a skin 'flush'. Thus, we have
      carried out a study of the breath metabolites of two healthy volunteers following
      (i) the ingestion of 200 mg of immediate-release niacin, (ii) as (i) but preceded
      by the ingestion of 325 mg of aspirin that diminishes the skin 'flush', (iii)
      ingestion of 500 mg of slow-release niacin. On-line breath analysis was carried
      out using selected ion flow tube mass spectrometry, SIFT-MS. The interesting new
      observation is that the breath ammonia levels of both volunteers clearly
      increased following (i) and (ii), and an obvious skin flush did occur following
      (i) but not following (ii). The slow-release niacin (iii) did not result in a
      flush and the breath ammonia levels increased more slowly and did not reach the
      higher levels produced by (i) and (ii). The results of these experiments
      demonstrate that breath ammonia levels are dependent on the blood/plasma levels
      of niacin, but are not directly related to the flushing phenomenon, and that the
      observed increases in blood/breath ammonia levels are consistent with current
      knowledge of the metabolic pathways of niacin. The parallel measurements of
      breath isoprene are presented, which demonstrate the quality of breath analyses
      that can be achieved using SIFT-MS.

PMID- 16603797
TI  - A comparison of lung function equipment with emphasis on interchangeability and
      methods.
AB  - The replacement of lung function equipment may not result in changing values:
      transitions should be seamless. We compared the equipment of two manufacturers
      (ZAN and Jaeger) to estimate the differences in spirometry, bodyplethysmography
      and diffusion capacity derived parameters elicited by equipment differences, and
      also compared calibration systems. From Jaeger (1) a Masterlab
      bodyplethysmograph, (2) a Pneumoscreen pneumotachograph, (3) a Masterscreen CS
      FRC and (4) a Masterlab CompactTransfer (the latter two measure the diffusion
      capacity) were compared, and from ZAN a bodyplethysmograph system encompassing
      spirometry, flow-volume curve and diffusion capacity measurements. In vitro (a 2
      litre calibration syringe at three flows, a fixed flow generator (0.5 l s(-1),
      1.67 l s(-1) and 5 l s(-1)) and a wave form generator) studies and an in vivo
      cross-over study (N = 59) were used to compare the pneumotachographs. Other
      parameters were compared only via the in vivo study. The calibration syringe
      study showed no differences between the pneumotachographs: all volumes in all
      systems were within 3% of the reference. The fixed flow generator showed no flow
      differences either: again within 3% of the reference. The wave form generator
      showed PEF, MEF(75/50/25) differences up to 10-15% from the reference, but none
      in FEV(1) and FVC. The in vivo study found similar system differences in PEF,
      MEF(75/50/25): up to 29%. FEV(1), VC and FVC differed by small amounts (in all
      cases <3% between systems). R(0.5), TLC, V(A) and RV differed by small amounts
      between the systems (in all cases <3%), but T(L,CO) up to 9%. This study showed
      that between and within manufacturers, significant differences can exist between
      pneumotachographs and that using calibration syringes or fixed flow generators
      these frequently go unnoticed. These approaches insufficiently test the dynamic
      features of pneumotachographs. For other parameters, in vivo calibration is the
      only option and accuracy is only achieved with rather large samples, so more
      research is needed into suitable in vitro systems.

PMID- 16603798
TI  - Compression of EMG signals with wavelet transform and artificial neural networks.
AB  - This paper presents a hybrid adaptive algorithm for the compression of surface
      electromyographic (S-EMG) signals recorded during isometric and/or isotonic
      contractions. This technique is useful for minimizing data storage and
      transmission requirements for applications where multiple channels with high
      bandwidth data are digitized, such as telemedicine applications. The compression
      algorithm proposed in this work uses a discrete wavelet transform for spectral
      decomposition and an intelligent dynamic bit allocation scheme implemented by an
      approach using the Kohonen layer, which improves the bit allocation for sections
      of the S-EMG with different characteristics. Finally, data and overhead
      information are packed by entropy coding. The results for the compression of
      isometric EMG signals showed that this algorithm has a better performance than
      standard wavelet compression algorithms presented in the literature (presenting a
      decrease of at least 5% in per cent residual difference (PRD) for the same
      compression ratio), and a performance that is comparable with the performance of
      algorithms based on an embedded zero-tree wavelet. For isotonic EMG signals, its
      performance is better than the performance of the algorithms based on embedded
      zero-tree wavelets (presenting a decrease in PRD of about 3.6% for the same
      compression ratios, in the useful compression range).

PMID- 16603799
TI  - Characterizing the normal heart using quantitative three-dimensional
      echocardiography.
AB  - We present normative data on cardiac volume, geometry and shape derived using
      three-dimensional echocardiography (3-DE). Three-dimensional reconstructions were
      created using the piecewise smooth surface subdivision (PSSS) reconstruction
      technique of the left and right ventricular (LV and RV) endocardium and the
      mitral and tricuspid annuli (MA and TA) of 67 normal subjects. We derived LV end
      diastolic (ED) and end-systolic (ES) volume indices (VI) of 76.5 +/- 16.8 ml m(
      2) and 35.3 +/- 14.1 ml m(-2), LV ejection fraction (EF) of 56.1 +/- 9.93%, RV
      EDVI and ESVI of 93.2 +/- 20.0 ml m(-2) and 49.9 +/- 13.5 ml m(-2) and RVEF of
      47.3 +/- 7.69%, along with data on the geometry and shape of the MA, TA, LV and
      RV. There was no pattern of consistent understatement or overstatement of volumes
      or dimensions compared with other imaging modalities, and observed variance in
      data can largely be accounted for through examination of the physics or protocol
      of each modality.

PMID- 16603794
TI  - Actions of neurotrophic factors and their signaling pathways in neuronal survival
      and axonal regeneration.
AB  - Adult axons in the mammalian central nervous system do not elicit spontaneous
      regeneration after injury, although many affected neurons have survived the
      neurotrauma. However, axonal regeneration does occur under certain conditions.
      These conditions include: (a) modification of regrowth environment, such as
      supply of peripheral nerve bridges and transplantation of Schwann cells or
      olfactory ensheathing glia to the injury site; (b) application of neurotrophic
      factors at the cell soma and axon tips; (c) blockade of growth-inhibitory
      molecules such as Nogo-A, myelin-associated glycoprotein, and oligodendrocyte
      myelin glycoprotein; (d) prevention of chondroitin-sulfate-proteoglycans-related
      scar tissue formation at the injury site using chondroitinase ABC; and (e)
      elevation of intrinsic growth potential of injured neurons via increasing
      intracellular cyclic adenosine monophosphate level. A large body of evidence
      suggests that these conditions achieve enhanced neuronal survival and axonal
      regeneration through sometimes overlapping and sometimes distinct signal
      transduction mechanisms, depending on the targeted neuronal populations and
      intervention circumstances. This article reviews the available information on
      signal transduction pathways underlying neurotrophic-factor-mediated neuronal
      survival and neurite outgrowth/axonal regeneration. Better understanding of
      signaling transduction is important in helping us develop practical therapeutic
      approaches for encouraging neuronal survival and axonal regeneration after
      traumatic injury in clinical context.

PMID- 16603800
TI  - Adaptive filtering of ECG interference on surface EEnGs based on signal
      averaging.
AB  - An external electroenterogram (EEnG) is the recording of the small bowel
      myoelectrical signal using contact electrodes placed on the abdominal surface. It
      is a weak signal affected by possible movements and by the interferences of
      respiration and, principally, of the cardiac signal. In this paper an adaptive
      filtering technique was proposed to identify and subsequently cancel ECG
      interference on canine surface EEnGs by means of a signal averaging process time
      locked with the R-wave. Twelve recording sessions were carried out on six
      conscious dogs in the fasting state. The adaptive filtering technique used
      increases the signal-to-interference ratio of the raw surface EEnG from 16.7 +/-
      6.5 dB up to 31.9 +/- 4.0 dB. In addition to removing ECG interference, this
      technique has been proven to respect intestinal SB activity, i.e. the EEnG
      component associated with bowel contractions, despite the fact that they overlap
      in the frequency domain. In this way, more robust non-invasive intestinal
      motility indicators can be obtained with correlation coefficients of 0.68 +/-
      0.09 with internal intestinal activity. The method proposed here may also be
      applied to other biological recordings affected by cardiac interference and could
      be a very helpful tool for future applications of non-invasive recordings of
      gastrointestinal signals.

PMID- 16603801
TI  - Factors affecting the use of cumulative sums in the analysis of circadian blood
      pressure.
AB  - The assessment of circadian blood pressure change by ambulatory blood pressure
      monitoring has potential as a predictor for cardiovascular events, but its
      evaluation is problematic due to the difficulty in defining day and night periods
      for individual subjects. The cumulative sums (cusums) method has the advantage of
      simplicity over mathematical modelling techniques and is reported to give more
      reproducible results than methods that use time-dependent sleep and wake periods.
      However, cusum parameters (cusum-derived circadian alteration magnitude (CDCAM)
      and cusum plot height (CPH)) are affected by the implementation of the method and
      by the quality of ambulatory blood pressure recordings. This study quantifies the
      effects of using interval blood pressure values, changing the time used for
      calculating the cusum plot slope (CPS) and using incomplete data recordings.
      Significant effects are reported in all cases. Using interval rather than
      recorded blood pressures causes a mean reduction in CPH and CDCAM of
      approximately 6%. Altering the CPS time by 1 h (from 6 h) results in a mean
      change in CDCAM of approximately 7%. In recordings with hourly readings, the
      coefficient of variation in CPH and CDCAM ranges from 4% (one missing reading) to
      13% (five missing readings).

PMID- 16603802
TI  - The detection of brain oedema with frequency-dependent phase shift
      electromagnetic induction.
AB  - The spectroscopic distribution of inductive phase shift in the brain as a
      function of the relative volume of oedema was evaluated with theoretical and
      experimental methods in the frequency range 1 to 8 MHz. The theoretical study
      employed a simple mathematical model of electromagnetic induction in tissue and
      brain tissue data available from the literature to calculate the phase shift as a
      function of oedema in the bulk of the brain. Experimental data were generated
      from bulk measurements of ex vivo homogenized pig brain tissue mixed with various
      volumes of physiological saline in a volume sample typical of the human brain.
      There is good agreement between the analytical and the experimental results.
      Detectable changes in phase shift begin from a frequency of about 3 MHz to 4 MHz
      in the tested compositions and volume. The phase shift increases with frequency
      and fluid content. The results suggest that measuring phase shift in the bulk of
      the brain has the potential for becoming a robust means for non-contact detection
      of oedema in the brain.

PMID- 16603803
TI  - Effects of dofetilide and EGIS-7229, an antiarrhythmic agent possessing class
      III, IV, and IB activities, on myocardial refractoriness in hyperkalemia,
      hypokalemia, and during beta-adrenergic activation in the rabbit papillary muscle
      in vitro.
AB  - Lengthening of the effective refractory period (ERP) by EGIS-7229, a class
      III/Ib/IV drug, and by dofetilide, a selective I(Kr) blocker, was compared in
      normokalemia (NK), hypokalemia (LK), and hyperkalemia (HK) in right ventricular
      papillary muscles of rabbits paced at 0.5, 1, and 2 Hz, in vitro, and also during
      beta-adrenergic activation. In NK, EGIS-7229 (3 and 10 microM) and dofetilide (30
      and 100 nM) similarly lengthened ERP in a steeply reverse frequency-dependent
      manner. The two compounds produced smaller ERP prolongations at 0.5 Hz in HK and
      LK, so rate-dependence of ERP changes decreased. EGIS-7229 lengthened ERP more at
      2 Hz than at 0.5 Hz at 10 microM in LK, that is, the effect of EGIS-7229 turned
      into positive frequency-dependence from 3 to 10 microM. Furthermore, EGIS-7229
      lengthened ERP at 10 microM more than dofetilide at 100 nM at 2 Hz stimulation
      rate (P<0.05). Isoproterenol (30 nM) eliminated the effect of dofetilide on ERP,
      while EGIS-7229 prolonged ERP during beta-adrenergic activation. In conclusion,
      efficacy of EGIS-7229 was superior to that of dofetilide in LK and during beta
      adrenergic stimulation, suggesting improved antiarrhythmic action for EGIS-7229
      under certain conditions in the patient.

PMID- 16603804
TI  - Role of substance P on histamine H(3) antagonist-induced scratching behavior in
      mice.
AB  - The purpose of the present study was to investigate the involvement of chemical
      mediators, other than histamine, in the scratching behavior induced by H(3)
      antagonists. Scratching behavior was induced by the histamine H(3) antagonists
      iodophenpropit and clobenpropit (10 nmol/site) when they were injected
      intradermally into the rostral part of the back of mast-cell-deficient (WBB6F1
      W/W(v)) and wild-type (WBB6F1 +/+) mice. Subsequently, the effect of spantide, a
      tachykinin NK(1) antagonist, was measured for 60 min. The effects of the H(3)
      antagonists on in vitro histamine release from rat peritoneal mast cells were
      also investigated. When spantide was injected intradermally at a dose of 0.5
      nmol/site, it significantly inhibited the response. Furthermore, iodophenpropit
      and clobenpropit (10(-6)-10(-8) M) did not induce histamine release in isolated
      rat peritoneal mast cells. Our results indicate that substance P is involved in
      the skin responses elicited by the histamine H(3) antagonists. Moreover, the fact
      that these histamine H(3) antagonists did not induce significant increases in the
      histamine release from rat peritoneal mast cells suggests that the histamine H(3)
      receptor may not be present in the peripheral cells considered in this study.

PMID- 16603805
TI  - The regulation of calcium/calmodulin-dependent protein kinase II during oocyte
      activation in the rat.
AB  - Increases in intracellular Ca2+ are required for oocyte activation and subsequent
      development. Calmodulin-dependent protein kinase II (CaMKII) plays a crucial role
      in oocyte activation. However, how CaMKII is regulated during this process is not
      well characterized. We show here for the first time in rat oocytes that CaMKII is
      phosphorylated during oocyte activation. CaMKII phosphorylation was suppressed by
      KN93, a CaMKII inhibitor, but not KN92, which is the inactive analogue of KN93.
      Electrical stimulation of rat oocytes resulted in degradation of both cyclin B
      and Mos, presumably due a rise in Ca2+ induced by the electrical pulse. KN93
      blocked the degradation of both proteins induced by the electrical pulse.
      Addition of a protein phosphatase inhibitor, okadaic acid (OA), further increased
      the amount of CaMKII and also increased the amount of phosphorylated enzyme.
      Importantly, in oocytes undergoing spontaneous activation, accumulation and
      phosphorylation of CaMKII also occurs in a time-dependent manner. Consistent with
      this, addition of KN93 inhibited spontaneous activation. Collectively, our
      results show that CaMKII is phosphorylated during oocyte activation and that this
      phosphorylation is involved in inactivation of p34cdc2 kinase and somewhat
      involved in degradation of Mos. Furthermore, CaMKII phosphorylation is negatively
      regulated by a protein phosphatase.

PMID- 16603806
TI  - Evidence from nuclear DNA sequences sheds light on the phylogenetic relationships
      of Pinnipedia: single origin with affinity to Musteloidea.
AB  - Considerable long-standing controversy and confusion surround the phylogenetic
      affinities of pinnipeds, the largely marine group of "fin-footed" members of the
      placental mammalian order Carnivora. Until most recently, the two major competing
      hypotheses were that the pinnipeds have a single (monophyletic) origin from a
      bear-like ancestor, or that they have a dual (diphyletic) origin, with sea lions
      (Otariidae) derived from a bear-like ancestor, and seals (Phocidae) derived from
      an otter-, mustelid-, or musteloid-like ancestor. We examined phylogenetic
      relationships among 29 species of arctoid carnivorans using a concatenated
      sequence of 3228 bp from three nuclear loci (apolipoprotein B, APOB;
      interphotoreceptor retinoid-binding protein, IRBP; recombination-activating gene
      1, RAG1). The species represented Pinnipedia (Otariidae: Callorhinus, Eumetopias;
      Phocidae: Phoca), bears (Ursidae: Ursus, Melursus), and Musteloidea (Mustelidae:
      Mustela, Enhydra, Melogale, Martes, Gulo, Meles; Procyonidae: Procyon; Ailuridae:
      Ailurus; Mephitidae: Mephitis). Maximum parsimony, maximum likelihood, and
      Bayesian inference phylogenetic analyses of separate and combined datasets
      produced trees with largely congruent topologies. The analyses of the combined
      dataset resulted in well-resolved and well-supported phylogeny reconstructions.
      Evidence from nuclear DNA evolution presented here contradicts the two major
      hypotheses of pinniped relationships and strongly suggests a single origin of the
      pinnipeds from an arctoid ancestor shared with Musteloidea to the exclusion of
      Ursidae.

PMID- 16603807
TI  - Genetic variation of the MHC DQB locus in the finless porpoise (Neophocaena
      phocaenoides).
AB  - The Major Histocompatibility Complex (MHC) is a large multigene coding for
      glycoproteins that play a key role in the initiation of immune responses in
      vertebrates. The exon 2 region of the MHC DQB locus was analyzed using 160
      finless porpoises from 5 populations in Japanese waters. The 5 populations were
      based on a previous mitochondrial DNA control region analysis, which showed
      distinct geographical separation. Eight DQB alleles were detected, and the
      geographical distribution of the alleles indicated that most of them are shared
      among the populations. Heterozygosity of the DQB alleles in each population
      ranged from 0.55 to 0.78, and for all 5 populations was 0.78. Low MHC variability
      is not a common feature in marine mammals, but the finless porpoise populations
      inhabiting coastal waters had a relatively high MHC heterozygosity. Balancing
      selection in the MHC DQB alleles of the finless porpoise was indicated by the
      higher rate of nonsynonymous than synonymous substitutions for PBR; however, an
      excess of hetrozygotes compared to expectation was not observed. This suggests
      that the MHC DQB locus in the finless porpoise may have been under balancing
      selection for a long evolutionary time period, and is influenced by genetic drift
      beyond the effect of balancing selection for short time periods in small local
      populations.

PMID- 16603808
TI  - Patterns of species description and species richness of geometrid moths
      (lepidoptera: geometridae) on the Korean peninsula.
AB  - The diversity and pattern of species description among geometrid moths in Korea
      from 1883 to 2004 were assessed. A total of 647 geometrid species have been
      described: Ennominae (275 species, 43%), Larentiinae (227 spp., 35%), Geometrinae
      (68 spp., 11%), Sterrhinae (67 spp., 11%), Oenochrominae (9 spp., 2%), and
      Archiearinae (1 sp., <1%). Fourteen authors described more than 80% of geometrid
      species. The cumulative curve of the number of geometrid species described showed
      three high-rate peaks of description, around the 1900s, 1950s, and 2000s. The
      cumulative curves of five subfamilies (Ennominae, Larentiinae, Geometrinae,
      Sterrhinae, and Oenochrominae) fluctuated equally, and none has clearly reached
      an asymptote. The localities where a species was first recorded in Korea are
      mostly in the northern and central parts of the peninsula. The utility of
      larentiines, which are predominant in mountainous habitats and high latitudes, as
      a bioindicator for global warming is briefly discussed.

PMID- 16603809
TI  - Light and scanning electron microscopic study of the tongue in the cormorant
      Phalacrocorax carbo (Phalacrocoracidae, Aves).
AB  - The tongue of the cormorant Phalacrocorax carbo is a small, immobile structure
      with a length of 1.4 cm, situated in the middle part of the elongated lower bill.
      The uniquely shaped tongue resembles a mushroom, with a short base and an
      elongated dorsal part with sharpened anterior and posterior tips. A median crest
      can be observed on the surface of the tongue. Examination by light and scanning
      electron microscopy revealed that the whole tongue is formed by a dense
      connective tissue with many bundles of elastic fibers. The lingual mucosa is
      covered by a multilayered keratinized epithelium. The thickest, horny layer of
      the lingual epithelium was observed on the surface of the median crest and on the
      posterior tip of the tongue. Lingual glands are absent in cormorants. The
      framework of the tongue is composed of a hyoid cartilage incorporated into the
      base. The localization and structure of the tongue in the cormorant show that it
      is a rudimentary organ and that the lingual body, usually well-developed in
      birds, is conserved.

PMID- 16603810
TI  - Morphology of foretarsal ventral surfaces of Japanese Papilio butterflies and
      relations between these morphology, phylogeny and hostplant preferring hierarchy.
AB  - Foretarsal ventral surface observation of Japanese Papilio butterflies showed
      that the shapes of fifth foretarsi and numbers and localization of contact
      chemosensilla and spines in these areas are closely related to both phylogeny and
      behavior in these species. My results basically supported the classification that
      Japanese Papilio divides into five subgenera -- Papilio (P. machaon), Princeps
      (P. xuthus and P. demoleus), Achillides (P. maackii and P. bianor), Menelaides
      (P. helenus, P. polytes, P. protenor and P. macilentus) and Iliades (P. memnon).
      Moreover, female foretarsal morphology also corresponded to the physical features
      of their preferring host plant leaves. The specificity of female P. machaon,
      female P. macilentus and female P. maackii seemed to also relate to the
      geographical diversities of these species and their hostplant, and their co
      evolution.

PMID- 16603811
TI  - Phylogenetic relationships within parrots (Psittacidae) inferred from
      mitochondrial cytochrome-b gene sequences.
AB  - Blood and tissue samples of 40 individuals including 27 parrot species (15
      genera; 3 subfamilies) were collected in Indonesia. Their phylogenetic
      relationships were inferred from 907 bp of the mitochondrial cytochrome-b gene,
      using the maximum-parsimony method, the maximum-likelihood method and the
      neighbor-joining method with Kimura two-parameter distance. The phylogenetic
      analysis revealed that (1) cockatoos (subfamily Cacatuinae) form a monophyletic
      sister group to other parrot groups; (2) within the genus Cacatua, C. goffini and
      C. sanguinea form a sister group to a clade containing other congeners; (3)
      subfamily Psittacinae emerged as paraphyletic, consisting of three clades, with a
      clade of Psittaculirostris grouping with subfamily Loriinae rather than with
      other Psittacinae; (4) lories and lorikeets (subfamily Loriinae) emerged as
      monophyletic, with Charmosyna placentis a basal sister group to other Loriinae,
      which comprised the subclades Lorius; Trichoglossus+Eos; and Chalcopsitta+
      Pseudeos.

PMID- 16603812
TI  - Blue and double-peaked green receptors depend on ommatidial type in the eye of
      the Japanese yellow swallowtail Papilio xuthus.
AB  - The compound eye of the butterfly Papilio xuthus is composed of three spectrally
      distinct types of ommatidia. We investigated the blue and double-peaked green
      receptors that are encountered distally in type I and III ommatidia, by means of
      intracellular recordings, in vivo fluorescence microscopy, and histology. The
      blue receptors are R1 and/or R2 photoreceptors; they contain the same mRNA
      encoding the opsin of the blue-absorbing visual pigment. However, here we found
      that the sensitivity in the UV wavelength region strongly depends on the
      ommatidial type; the blue receptors in type I ommatidia have a distinctly
      depressed UV sensitivity, which is attributed to lateral filtering in the fused
      rhabdom. In the main, fronto-ventral part of the eye, the R3 and R4
      photoreceptors of all ommatidia contain the same set of two mRNAs encoding the
      opsins of green-absorbing visual pigments, PxL1 and PxL2. The spectral
      sensitivities are double-peaked, but the UV sensitivity of the R3 and R4
      photoreceptors in type I ommatidia appears to be reduced, similar to that of the
      co-localized blue receptors.

PMID- 16603813
TI  - Reproductive swarming of sympatric nereidid polychaetes in an estuary of the
      Omuta-gawa river in Kyushu, Japan, with special reference to simultaneous
      swarming of two Hediste species.
AB  - Habitat differences and spatial and temporal separation in reproductive swarming
      among sympatric nereidid polychaetes were examined in an estuary of the Omuta
      gawa River, Kyushu, Japan by annual periodical sampling from December 2003 to
      January 2005. Benthic adults of Tylorrhynchus osawai and Hediste diadroma
      occupied mainly the upper reaches of the estuary, whereas those of H. japonica
      usually inhabited the middle reaches, though their distributions overlapped.
      Reproductive swarming of mature adults occurred in the estuary just after high
      tide at night during spring tides in four nereidids: H. japonica (in the middle
      and lower reaches from late December to late February), H. diadroma (throughout
      the whole estuary from middle December to late April), T. osawai (in the middle
      reaches and another estuary from late October to late December), and
      Nectoneanthes oxypoda sensu Imajima, 1972 (in the lower reaches in late April and
      early May). This result shows that temporal separation of reproductive swarming
      may act as a reproductive isolation mechanism among these nereidids, except for
      H. japonica and H. diadroma. Simultaneous swarming and mass-spawning of the two
      Hediste species were commonly observed in the middle and lower reaches from late
      December to early February, suggesting the absence of a pre-spawning barrier to
      reproductive isolation between them. We found no difference in spawning behavior
      between H. japonica and H. diadroma. Males of both species seemed to participate
      in swarming earlier than females.

PMID- 16603814
TI  - Distinct specific status of the Korean brown frog, Rana amurensis coreana
      (Amphibia: Ranidae).
AB  - We used morphological and genetic data to assess the taxonomic status of Rana
      amurensis coreana and R. a. amurensis. Morphological comparisons revealed these
      two subspecies to be different from each other in size of body, nature of
      tubercles on dorsal stripe, degree of development in toe webbing, and condition
      of lateral spots of trunk. They were also different in sequence of mitochondrial
      16S rRNA gene, with genetic distance as large as those observed among different
      species of brown frogs. Therefore, Korean populations previously considered a
      subspecies of R. amurensis should be regarded as a distinct species (=R.
      coreana).

PMID- 16603815
TI  - Genetic diversity of nine populations of the black goat (Capra hircus) in
      Sichuan, PR China.
AB  - Sixteen polymorphic primers screened from 100 random primers were selected to
      analyze the randomly amplified polymorphic DNA (RAPD) of 540 domesticated black
      goats (Capra hircas) from 9 different geographical populations in Sichuan
      Province of China. After the test, 170 entirely repeatable RAPD markers
      representing goat polymorphisms were obtained from the 16 polymorphic primers,
      the lengths of the markers ranging from 0.1 to 2.5 kb. The genetic distance among
      the black goat populations ranges from 0.1051 to 0.2978. The similarity
      coefficient (0.9002) between Jintang and Lezhi black goats was the highest in the
      9 populations, followed by the coefficient (0.8953) between Jialing and Yinshan
      goats, while that between Jiangan and Huili goats was found to be the lowest
      (0.7424). The coefficient of differentiation among population genes (Gst) was
      0.2766, indicating a comparatively low degree of differentiation among the black
      goat populations. A UPGMA dendrogram constructed from similarity coefficients
      showed that the two populations from Huili and Baiyu, which are found mostly on
      the Western Sichuan plateau and in mountainous areas, clustered together, and the
      other seven populations formed another group. It can also be clearly seen that
      the Huili and Baiyu populations are very special, and must have been closely
      related in the past, even though their link with the other populations is quite
      weak as a result of genetic communication. The results of the experiment offer
      some crucial scientific data useful for the breeding of black goats.

PMID- 16603816
TI  - Comparison of two methods of attaching telemetry transmitters to the Mekong giant
      catfish, Pangasianodon gigas.
AB  - For conservation and successful stock enhancement of endangered species, an
      understanding of the movement patterns and behavior of the target species is
      indispensable. The Mekong giant catfish, Pangasianodon gigas, is endemic to the
      Mekong Basin and now is threatened with extinction. Although biotelemetry using
      acoustic transmitters and receivers is expected to reveal its movement patterns
      and behavior, the most suitable attachment method for the transmitter to the
      catfish is unknown. In this study we examined the effects of external attachment
      and surgical implantation on the survival and growth of the catfish, compared
      with those in control individuals, in an earthen fish pond for approximately 2
      months. No fish died during the experimental period. Furthermore, we found no
      fungal infections in any fish and no significant differences in growth rate among
      treatment and control fish. However, all transmitters of externally tagged fish
      were lost during the experimental period. In contrast, transmitters of some
      surgically implanted fish remained in the peritoneal cavity. In conclusion, the
      surgical implantation technique is suitable for long-term monitoring of the
      catfish.

PMID- 16603817
TI  - Uncompetitive inhibition of Xenopus laevis aldehyde dehydrogenase 1A1 by divalent
      cations.
AB  - Aldehyde dehydrogenases (ALDHs) convert aldehydes into their corresponding
      carboxylic acids. ALDH1A1, also known as ALDH class 1 (ALDH1) or retinaldehyde
      dehydrogenase (RALDH1), prefers retinal to acetaldehyde as a substrate. To
      investigate the effects of divalent cations on the dehydrogenase activity of
      Xenopus laevis ALDH1A1, the formation of acetate and retinoic acid from
      acetaldehyde and retinal, respectively, was investigated in the presence of Ca2+,
      Mg2+, Mn2+ or Zn2+. All divalent cations tested inhibited the oxidation of
      acetaldehyde and retinal by ALDH1A1. When acetaldehyde was used as a substrate,
      the 50% inhibitory concentrations (IC50) were 10, 24, 35 and 220 microM for Zn2+,
      Mn2+, Mg2+ and Ca2+, respectively. Kinetic studies of ALDH1A1 dehydrogenase
      activity in the presence or absence of each cation revealed that the inhibition
      mode by cations was uncompetitive against acetaldehyde, retinal, and NAD+, and
      that their inhibitory potencies were greater against acetaldehyde than retinal.
      It was concluded that the divalent cations inhibited X. laevis ALDH1A1 activity
      in a substrate-dependent manner by affecting a step of the dehydrogenase reaction
      that occurred after the formation of the ternary complex of the enzyme,
      substrate, and coenzyme.

PMID- 16603818
TI  - In vitro culture of mesenchymal lineage cells established from the colonial
      tunicate Botryllus primigenus.
AB  - Body trunks were isolated from juvenile zooids of the Japanese colonial tunicate
      Botryllus primigenus and cultured in vitro to establish tissue-specific cell
      lines. Epidermal cells from some explants spread and formed a flat sheet
      consisting of vacuolated cells. They then dissociated into single cells, and
      their growth stopped within two weeks. Continuously proliferating cells were
      established from four explants. After the 20th implantation, nuclear and
      mitochondrial DNAs were extracted from these cells. The nucleotide sequences of
      proliferating cell nuclear antigen (PCNA) and mitochondrial large ribosomal RNA
      (mtlrRNA) completely matched the PCNA and mtlrRNA taken from living colonies of
      B. primigenus; this shows that the four independently proliferating cells were
      indeed of the Botryllus origin. One cell line (Bp0306E10) comprised round-shaped
      cells with a diameter of 8-10 microm. These cells have been cultured in vitro
      with a doubling time of approximately 24 hours since June, 2003. The BrdU
      labeling index was approximately 2%. Monoclonal antibodies raised against the
      cultured cells recognized a 28 kDa polypeptide and stained free mesenchymal cells
      in vivo. G418-resistant subclonal cells could be established by introducing a
      tunicate retrotransposon loaded with the neomycin resistance gene into the cells
      by electroporation. This study is the first to succeed in producing a sustainable
      cell culture of Botryllus.

PMID- 16603819
TI  - Long tails affect swimming performance and habitat choice in the male guppy.
AB  - Sexual selection often favors male secondary sexual traits, although in some
      cases the elaborate traits incur costs to the males with respect to natural
      selection. Males of the guppy Poecilia reticulata have longer tails (caudal fins)
      than females, and the long tails contribute to the mating success of the males
      through female mate choice. We examined the effect of tail length on the swimming
      performance of male and female guppies. In a laboratory experiment, males with
      longer tails exhibited poorer swimming performance than those with shorter tails.
      However, this effect was not apparent in females. In addition, in a feral
      population, tail length of males was negatively correlated with water flow
      velocity in their microhabitats. Although body size of females was negatively
      correlated with water flow velocity in their microhabitats, tail length of
      females showed no significant correlation with degree of water flow. These
      results suggest that the long tail of male guppies incurs costs, such as a
      decrease in swimming performance, to the males with respect to natural selection
      and consequently limits their choice of habitats to those with slow water flow.

PMID- 16603820
TI  - Morphological and molecular revision of Zoanthus (Anthozoa: Hexacorallia) from
      southwestern Japan, with descriptions of two new species.
AB  - No clear method of identifying species in the zoanthid genus Zoanthus has been
      established, due in part to the morphological plasticity of this genus (e.g., in
      polyp and colony form, oral disk color, tentacle number). Previous research
      utilizing the mitochondrial cytochrome oxidase I gene (COI) as a phylogenetic
      marker indicated that Zoanthus spp. in Japan may consist of only one or two
      species, despite a bewildering variety of observed morphotypes. Here we have
      utilized not only COI but also mitochondrial 16S ribosomal DNA (mt 16S rDNA) in
      order to clarify the extent of Zoanthus species diversity in southern Japan. Our
      molecular genetic results clearly show the presence of three monophyletic
      Zoanthus species groups with varying levels of morphological plasticity,
      including the new species Z. gigantus n. sp. and Z. kuroshio n. sp. We describe
      all three species found in this study, and identify potential morphological
      characters (coenenchyme and polyp structure as well as polyp external surface
      pigmentation patterns) useful in Zoanthus species identification. A morphological
      dichotomous key is provided to assist in field species identification.

PMID- 16603821
TI  - Neural interaction of gonadotropin-regulating hormone immunoreactive neurons and
      the suprachiasmatic nucleus with the paraventricular organ in the Japanese grass
      lizard (Takydromus tachydromoides).
AB  - Our previous study demonstrated that the paraventricular organ (PVO) in the
      hypothalamus of the Japanese grass lizard (Takydromus tachydromoides) showed
      immunoreactivity against the light signal-transducing G-protein, transducin. This
      finding suggested that the PVO was a candidate for the deep-brain photoreceptor
      in this species. To understand functions of the PVO, we investigated
      distributions of transducin, serotonin, gonadotropin-releasing hormone (GnRH),
      and gonadotropin-inhibitory hormone (GnIH) in the lizard's brain. We
      immunohistochemically confirmed co-localization of transducin and serotonin in
      PVO neurons that showed structural characteristics of cerebrospinal fluid (CSF)
      contacting neurons. GnRH-immunoreactive (ir) cells were localized in the
      posterior commissure and lateral hypothalamic area. Some of the serotonin-ir
      fibers extending from the PVO to the lateral hypothalamic area contacted the GnRH
      ir cell bodies. GnIH-ir cells were localized in the nucleus accumbens,
      paraventricular nucleus, and upper medulla, and GnIH-ir fibers from the
      paraventricular nucleus contacted the lateral processes of serotonin-ir neurons
      in the PVO. In addition, we found that serotonin-ir fibers from the PVO extended
      to the suprachiasmatic nucleus (SCN), and the retrograde transport method
      confirmed the PVO projections to the SCN. These findings suggest that the PVO, by
      means of innervation mediated by serotonin, plays an important role in the
      regulation of pituitary function and the biological clock in the Japanese grass
      lizard.

PMID- 16603822
TI  - The variability of cranial morphology in modern horses.
AB  - Horses bred nowadays are characterized by high variability of the body build. The
      variability concerns exterior features and skeleton features. From among the
      skeleton parts the skull is an element influenced by selection and environmental
      adaptation. The aim of these investigations was to find whether cranial traits
      exhibit variability in relation to the body build of horses. To do this, metric
      parameters of skulls of 43 horses used in the investigations were analysed with
      various statistical techniques. On the basis of ANOVA, Principal Components
      Analysis and Canonical Discriminant Analysis it was found that horses of various
      constitutional types exhibit differences in cranial morphology. Warm blood horses
      of the respiratory constitutional type have more complex nasal cavity from horses
      of heavier body build. A meaningful effect on craniometric variability was
      observed in the length and breadth of the viscerocranium. Also the height of the
      viscerocranium--a cranial feature of the respiratory tract, showed a high
      discriminating power.

PMID- 16603823
TI  - Apoptosis and adhesion of hemocytes during molting stage of silkworm, Bombyx
      mori.
AB  - To clarify the regulatory mechanism of the rapid changes in the hemocyte density
      in the silkworm, Bombyx mori, during ecdysis, we evaluated the relationship
      between the hemocyte density and the incidence of apoptosis during this stage. We
      also evaluated the role of the sugar chains on the adhesion of hemocytes by
      analyzing the effects on the hemocyte density of the injection of enzymes that
      cut sugar chains and monosaccharides into the body cavity. The hemocyte density
      was increased in the molting stage and spinning, and then decreased after the
      ecdysis. During spinning, the diameter of the granulocytes markedly increased, in
      which fatty granules in the cytoplasm increased, becoming foamy. They were
      identified to be apoptotic hemocytes using the Hoechst staining and the Comet
      assay. The decrease in the hemocyte density during spinning was mainly caused by
      the apoptosis of granulocytes. Next, we focused on the fluctuation of hemocyte
      density during the molting stage. Examination of the changes in the hemocyte
      density induced by injecting glycoside hydrolases, neuraminidase, sialic acid, or
      monosaccharides into the body cavity during the fourth molt stage and the third
      day in fifth instar larva demonstrated that the alteration of hemocyte density
      was regulated by the attachment and detachment of hemocytes via a selectin
      ligand, sugar chains. As with the injection of glycoside hydrolase,
      neuraminidase, sialic acid and fucose raised the hemocyte detachment, and it was
      assumed that the selectin ligands include the sialyl Lewis x like sugar chains,
      the same as mammalian lymphocytes.

PMID- 16603824
TI  - Antioxidant intake and coronary atherosclerosis: consider a "foods first"
      approach.

PMID- 16603825
TI  - Antioxidant vitamin intake and subclinical coronary atherosclerosis.
AB  - Numerous studies have evaluated the association between antioxidants and coronary
      atherosclerosis but have been limited by its study among individuals with
      advanced atherosclerosis. The authors studied 865 consecutive patients, 39-45
      years of age, without known coronary artery disease and presenting for a periodic
      physical examination. Antioxidant intake was assessed with the Block Dietary
      Questionnaire, and coronary atherosclerosis was identified by measuring coronary
      artery calcification using electron beam computed tomography. The mean age was 42
      (+/-2), 83% were male, and the prevalence of coronary artery calcification was
      20%. Vitamin supplements were used by 56% of the participants, and the mean (+/
      SD) daily intake (dietary plus supplemental) of vitamins A, C, and E were 1683 mg
      (+/-1245), 371 mg (+/-375), and 97 mg (+/-165), respectively. There was no
      significant correlation between coronary artery calcification score and
      individual vitamin or total antioxidant vitamin intake, even after adjusting for
      traditional cardiac risk factors. The highest quartile of vitamin E was
      positively associated with calcification (odds ratio=1.77; 95% confidence
      interval, 1.02-3.06). Antioxidant vitamin intake is not significantly related to
      coronary artery calcification, implying that there is no effect on the
      development of early coronary atherosclerosis. High doses of vitamin E may confer
      an increased risk of calcified atherosclerosis.

PMID- 16603826
TI  - Lipid profile correlates with glycemic control in young patients with type 1
      diabetes mellitus.
AB  - Data on dyslipidemia in type 1 diabetes is scarce. The authors aimed to evaluate
      the lipid profile in patients with type 1 diabetes and its correlation to
      glycemic control. Ninety-four subjects (53.2% males), aged 15.4+/-4.7 (3.6-21.9
      years), with disease duration of 5.0+/-3.6 years (0.3-17 years) were evaluated
      for heart rate, blood pressure, height, and weight. Laboratory data included
      total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein
      (LDL), triglycerides (TGs), glycemia, glycosylated hemoglobin (HbA1c),
      creatinine, thyroid-stimulating hormone, antithyroid antibodies, and 24-hour
      microalbuminuria. Correlations were performed by the Spearman rank correlation
      test, and the significance level was <0.05. Mean values were TC, 168.6+/-46.6
      mg/d; HDL, 43.1+/-15.3 mg/dL; LDL, 110.9+/-40.6 mg/dL; TGs, 78.3+/-48.6 mg/dL;
      glycemia, 204.6+/-116.7 mg/dL; and HbA1c, 11.2%+/-2.9%. High TC (43.9% vs. 10.7%;
      p<0.002) and LDL (51.5% vs. 10.7%; p<0.01) were more prevalent in patients 19
      years and younger (n=66). HbA1c correlated with TC (r=0.30; p=0.004), LDL
      (r=0.28; p=0.008), TG (r=0.31; p=0.003), and TG/HDL ratio (r=0.25; p=0.01).
      Duration of diabetes correlated with LDL (r=0.21; p=0.04) and insulin daily doses
      with TG (r=0.23; p=0.04) and body mass index expressed as z scores (r=-0.28;
      p=0.007). There was a high prevalence of hypercholesterolemia (54.6%) in these
      diabetic patients, and lipid fraction levels were correlated with HbA1c. Good
      management of diabetes seems to be of paramount importance in controlling
      dyslipidemia.

PMID- 16603827
TI  - Rationale for intensive statin treatment in high-risk patients.
AB  - Intensive lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitors (statins) is now an established regimen for patients at high
      risk for cardiovascular events, regardless of baseline low-density lipoprotein
      cholesterol levels. Treatment with statins to reduce low-density lipoprotein
      cholesterol levels significantly below 100 mg/dL has been shown to further reduce
      the risk of cardiovascular morbidity and mortality in high-risk patients and has
      provided the necessary data for an update to the National Cholesterol Education
      Program's Third Adult Treatment Panel (ATP III) guidelines. Intensive statin
      therapy is also well tolerated, with no increased risk of noncardiovascular
      adverse events and a low incidence of clinically significant liver or muscle
      enzyme abnormalities. Results of recent clinical and surrogate end point trials
      confirm that intensive lowering of low-density lipoprotein cholesterol is
      beneficial and safe in a majority of high-risk patients.

PMID- 16603828
TI  - Beta blockade in the post-myocardial infarction setting: pharmacologic rationale
      and clinical evidence.
AB  - The use of beta blockers reduces the risk of arrhythmias, reinfarction, and heart
      failure in both the immediate and long-term periods after a myocardial
      infarction. Every patient should be prescribed a beta blocker after a myocardial
      infarction unless there is a strong contraindication to therapy. Despite
      compelling evidence and recommendations, beta blockers remain an underutilized
      therapy in the post-myocardial infarction period. Evidence-based recommendations
      for the choice of agent and the practical implementation of beta blockers are
      reviewed.

PMID- 16603829
TI  - Lipid management reduces cardiovascular complications in individuals with
      diabetes and prediabetes.
AB  - Patients with type 2 diabetes are known to have an elevated risk of
      cardiovascular morbidity and mortality. Prior to the development of hyperglycemia
      and type 2 diabetes, individuals undergo a prolonged prediabetic phase involving
      hyperglycemia and insulin resistance. This has been associated with increased
      cardiovascular risk and is considered a cardiovascular risk equivalent. It is
      well known that dyslipidemia is an important contributor to the development of
      coronary artery disease. Treating diabetes with lipid-lowering agents reduces
      patients' cardiovascular risk. Preliminary studies have shown that similar
      benefits are seen even in persons with prediabetes. Hence, lipid-lowering agents
      should be considered not only in patients with type 2 diabetes, but also in
      individuals with prediabetes and with elevated lipid levels.

PMID- 16603830
TI  - Muraglitazar and the FDA: what constitutes drug safety?

PMID- 16603831
TI  - IDEAL and FIELD.

PMID- 16603832
TI  - The low-fat diet that "wasn't".

PMID- 16603834
TI  - Who knows best? The patient or the physician?

PMID- 16603835
TI  - Effects of psoralen-UV-A-Turban in alopecia areata.
AB  - BACKGROUND: Psoralen-UV-A (PUVA)-turban is a modification of PUVA-bath therapy
      used in alopecia areata. OBJECTIVE: The aim of this study was to assess the
      efficacy of PUVA-turban in different forms of alopecia areata. Twenty patients
      completed the study: nine with alopecia areata vulgaris and 11 with alopecia
      areata totalis or universalis. METHODS: 8-methoxypsoralen in a dilution of
      0.0001% (1 mg/L) was administered to the scalp for 20 minutes using a cotton
      towel as a turban. The application was followed by UV-A radiation. Treatments
      were performed two or three times weekly. The cumulative doses ranged from 48.2
      253.4 J/cm2, and single fractions ranged from 0.3-6.5 J/cm2. RESULTS: Hair
      regrowth was observed in 15 patients (total regrowth in six patients and partial
      regrowth in nine patients). Five patients did not respond to the therapy.
      CONCLUSIONS: PUVA-turban was significantly more effective in alopecia areata
      vulgaris than in alopecia areata totalis or universalis and proved to be a safe,
      well tolerated method without the systemic side effects of PUVA.

PMID- 16603836
TI  - Pemphigus vulgaris in Iran: epidemiology and clinical profile.
AB  - BACKGROUND: Although the clinical profile of pemphigus vulgaris is generally well
      characterized, the epidemiologic differences are important but not widely
      evaluated. This study was conducted to evaluate the incidence and clinical
      profile of pemphigus patients in a large central province of Iran. METHODS:
      Demographic variables, clinical manifestations, and side effects of treatment in
      188 patients in a 10-year period were studied. RESULTS: The annual incidence rate
      of pemphigus vulgaris was 5/100,000, with a 1.6:1 ratio of incidence in women
      compared with men. The mean age of onset was 41.1+/-13.7 years. In 74% of
      patients, the initial presentation of the disease was mucosal involvement, and in
      the remaining 26% the disease initially presented on the skin. CONCLUSIONS:
      Iranian patients have a relatively young age of onset of pemphigus and a higher
      incidence among women than men, which may reflect geographic, cultural, dietetic,
      or racial differences in the clinical and biologic behavior of the disease.

PMID- 16603837
TI  - Skin basement membrane zone: a depository for circulating microbial antigen
      evoking psoriasis and autoimmunity.
AB  - BACKGROUND: Elevated levels of antibody to streptococcal exoenzymes have been
      found in patients with psoriasis or psoriatic arthritis. Research on the role of
      streptococcal antigen in psoriasis has been hampered by a potential molecular
      mimicry between streptococcal epitopes and human epidermal keratin. OBJECTIVE AND
      METHODS: Evidence of microbial product was sought in skin biopsies of psoriasis
      patients thought clinically to have either streptococcal carrier state or
      gastrointestinal candidal colonization. A polyclonal antibody to streptococcal
      derived exoenzymes unlikely to share antigenic structures with normal human skin,
      and an anticandidal antibody, were used with linked streptavidin biotin
      amplification stain. RESULTS: The predicted microbial product appeared heavily in
      lesional epidermis, but unexpectedly also as a thin deposit along the skin
      basement membrane zone (SBMZ) of apparently unaffected skin. Staining was
      negative for nonpsoriatic subjects. CONCLUSIONS: The findings support a direct
      effect of microbial antigen in psoriasis. They also suggest an important role for
      SBMZ as a very large adhesive surface in the first step of a process of
      percutaneous epidermal elimination of foreign antigens and microbial toxins. The
      many autoimmune phenomena seen so often at the SBMZ are probably a physiologic
      part of this important immune function. Efforts to enhance the adhesive
      properties of SBMZ should be exploitable for both diagnostic and therapeutic
      benefit.

PMID- 16603838
TI  - Photo capsules. Secondary syphilis.

PMID- 16603839
TI  - Tretin-X (tretinoin).

PMID- 16603840
TI  - Diagnosis and management of atypical fibroxanthoma.
AB  - A 90-year-old Caucasian man with a history of basal cell carcinoma and squamous
      cell carcinoma presented with a friable erythematous nodule on his scalp that had
      been present for several months. The lesion measured 1.4 x 1.8 cm. What is your
      diagnosis? How would you proceed?

PMID- 16603841
TI  - Sexually transmitted infections: points of interest for 2006.
AB  - The patterns of sexually transmitted infections vary tremendously in different
      parts of the world. Generalizations need to be taken with care. This paper will
      highlight some of the varied aspects of sexually transmitted infections today,
      including HIV/AIDS, syphilis, and lymphogranuloma venereum.

PMID- 16603842
TI  - Psoriatic erythroderma associated with enalapril.
AB  - A 59-year-old man with a 35-year personal and positive family history of
      psoriasis was admitted to our department for treatment of psoriatic erythroderma.
      The patient had commenced therapy with enalapril 10 mg b.i.d. for the treatment
      of hypertension approximately 6 weeks before hospitalization. Five weeks after
      the initiation of enalapril, his psoriasis began to flare, and for a period of
      about 1 week it reached the extent of erythroderma. The patient did not associate
      the psoriatic flare with other factors such as infections, trauma, or stress. The
      patient presented with diffuse erythema and pronounced desquamation covering his
      entire trunk, scalp, and extremities (Figure). Nearly 100% of the body surface
      area was involved. The palms and soles were also affected, displaying erythema,
      hyperkeratosis, and painful fissures. The nails showed pits, oil spots, and
      subungual hyperkeratosis. The patient also had psoriatic arthritis affecting the
      interphalangeal joints of his fingers. Laboratory tests revealed an elevated
      erythrocyte sedimentation rate, an elevated creatinine level of 180 mmol/L, a
      blood urea nitrogen level of 10.8 mmol/L, and a uric acid level of 716 mmol/L.
      Urinalysis showed proteinuria of 1.5 g/24 h. The patient's renal condition was
      diagnosed as chronic tubulointerstitial nephritis, most probably related to his
      dermatologic disease. Allopurinol and dietary measures were recommended.
      Following treatment with methotrexate and replacement of enalapril therapy, the
      erythema and scaling gradually subsided and became confined to his pre-eruptive
      chronic plaques (approximately 5% of body surface area). Rechallenge with
      enalapril was not performed.

PMID- 16603843
TI  - Tumid lupus erythematosus: an unusual scleredema-like presentation.
AB  - A 43-year-old white man presented with an 8-month history of redness and swelling
      on the back of the neck. He also noted a decrease in range of motion of his upper
      body. There was no improvement with a 4-week course of topical corticosteroids.
      Review of systems was negative for polydipsia, polyuria, polyphagia, and bone
      pain. His medical history included depression, gastroesophageal reflux disease,
      and microdiscectomy. His medications included sertraline and omeprazole. Physical
      examination revealed a 20-cm erythematous, indurated plaque on the posterior part
      of the upper back and neck (Figure 1). A lack of skin wrinkling was noted with
      lateral pressure. Biopsy revealed a periadnexal and mild interface dermatitis
      with an increase in connective tissue mucin as demonstrated with colloidal iron
      (Figures 2A and 2B). Serum protein electrophoresis, hemoglobin A1C, and
      antinuclear antibody titer were within normal limits. A diagnosis of tumid lupus
      erythematosus mimicking scleredema was made. Hydroxychloroquine therapy was
      started at a dose of 200 mg and, at 2 months' follow-up, the patient's symptoms
      and appearance were improved.

PMID- 16603844
TI  - Ulcerative paraneoplastic dermatomyositis secondary to metastatic breast cancer.
AB  - A 40-year-old Chinese-American woman with breast carcinoma metastatic to her
      lungs presented with a 3-month history of erosions on her inner thighs (Figure 1)
      and medial left shoulder. Faint livedo reticularis was evident on her legs as
      well. She had difficulty in walking and raising her shoulders. Her cutaneous
      examination was also notable for cuticular erythema (Figure 2) and mild
      periorbital erythema and edema. She had no systemic or rheumatologic complaints
      other than some difficulty in swallowing. Her blood chemistry values were notable
      for a creatinine kinase of 564 IU/L (5-200 IU/L), alanine aminotransferase 161
      U/L (0-40 U/L) and aspartate aminotransferase 93 U/L (0-40 U/L), and an
      antinuclear antibody titer of 1:2560. Other blood chemistries and antibody
      serologies (anti-Jo-1, anti-Mi-2 and other anti-tRNA synthetase, anti-Ro/SSA,
      anti-U1RNP, anti-PM/Scl, and anti-Ku) were within normal limits. A biopsy
      specimen was obtained from an area of intact skin close to a right thigh
      ulceration that showed subtle vacuolar alteration at the dermo-epidermal junction
      with occasional necrotic keratinocyte (Figure 3). Melanophages and telangiectases
      were present. Within the subcutis there was fibrin deposition and neutrophils. A
      diagnosis of dermatomyositis was made. The patient received oral prednisone 20 mg
      three times a day, and her ulcerations resolved. Her creatinine kinase, alanine
      aminotransferase, and aspartate aminotransferase values returned to normal over
      the course of 3 weeks, but her antinuclear antibody was unchanged. Radiographic
      studies concurrently noted that her breast cancer had recurred in her lungs;
      plans were made to treat her with chemotherapy. The patient was lost to close
      follow-up, but it was learned that her erosions had reoccurred while her
      prednisone was tapered and resolved when her dosage of prednisone was increased.

PMID- 16603845
TI  - Pyoderma gangrenosum related to a new granulocyte colony-stimulating factor.
AB  - A 23-year-old Caucasian man diagnosed with stage IVB Hodgkin's disease was
      referred to a university oncology section after completing 1.5 cycles of
      chemotherapy. His chemotherapy consisted of doxorubicin HCL, bleomycin,
      dacarbazine, and vinblastine, with prophylactic administration of a granulocyte
      colony stimulating factor. He had developed postchemotherapy complications of
      possible cellulitis and necrotizing fasciitis that required wound debridement.
      The wound and tissue cultures were negative. Biopsies taken at the time revealed
      a dense inflammatory infiltrate consistent with an abscess. Over the course of 2
      months, the wound healed with systemic antibiotics. The patient was reluctant to
      resume chemotherapy for his Hodgkin's disease because of his previous presumed
      skin infections. However, positive emission tomographic scanning revealed disease
      progression. Doxorubicin, bleomycin, dacarbazine, and prophylactic pegfilgrastim
      (a granulocyte colony-stimulating factor), were administered. Vinblastine was
      excluded from the new regimen. Shortly after chemotherapy and an injection of
      pegfilgrastim, the patient developed poorly defined, rapidly progressive
      erythema, edema, and pain in his right forearm. He presented to the emergency
      room, was evaluated by the orthopedics service, and taken to the operating room
      for debridement of suspected necrotizing fasciitis. When the dermatology service
      consulted the following day, the patient had developed an erythematous,
      edematous, tender plaque on his chest. After developing two additional lesions
      that began to ulcerate despite treatment with imipenem, vancomycin, clindamycin,
      rifampin, and gentamicin, the patient consented to a skin biopsy. His wound
      cultures continued to be negative.

PMID- 16603846
TI  - Emerging future issues in HIV/AIDS social research.

PMID- 16603847
TI  - Complete removal of HIV-1 RNA and proviral DNA from semen by the swim-up method:
      assisted reproduction technique using spermatozoa free from HIV-1.
AB  - BACKGROUND: Use of antiretroviral drugs has reduced the mortality rate for HIV
      infection and many HIV-discordant couples wish to have children. It is possible
      for an HIV-infected man to father children without risk of HIV transmission if
      HIV-free spermatozoa can be obtained from his semen. METHODS: An improved swim-up
      method was used to collect HIV-free spermatozoa from the semen of HIV-positive
      males. Diluted semen was layered over a Percoll solution with a continuous
      density gradient of 30-98%, and then centrifuged. The bottom layer was collected
      by cutting the end from the tube and the sperm suspension was collected using the
      swim-up method. Spermatozoa were tested by nested polymerase chain reaction (PCR)
      for HIV-1 RNA and DNA, with a detection limit of one copy. Spermatozoa were used
      for assisted reproduction in 43 couples. RESULTS: HIV-1 RNA and proviral DNA were
      not detected by nested-PCR assay in all 73 of the collected spermatozoa samples
      from 52 patients. The HIV-1-negative sperm was used for in vitro fertilization in
      12 couples and for intracytoplasmic sperm injection in 31 couples. No detection
      of HIV-1 RNA or proviral DNA in the culture medium of the fertilized eggs was
      confirmed again before embryo transfer. Of the 43 female partners, 20 conceived
      and 27 babies were born. HIV antibodies, HIV RNA and proviral DNA were negative
      in all of the females and babies. CONCLUSIONS: HIV-negative spermatozoa could be
      obtained from semen of HIV-positive men. The method involves no risk of HIV
      transmission to female partners and their children.

PMID- 16603848
TI  - A killer mimotope with therapeutic activity against AIDS-related opportunistic
      micro-organisms inhibits ex-vivo HIV-1 replication.
AB  - OBJECTIVE: To verify whether a synthetic therapeutic killer decapeptide (KP), a
      functional mimotope of a yeast killer toxin with wide-spectrum microbicidal
      activity, inclusive of AIDS-related opportunistic micro-organisms, through
      interaction with beta-glucan receptors, which has been found to possess sequence
      homology with critical segments in gp160 V1/V2 and V3 loops, may also be
      inhibiting HIV-1 replication. METHODS: Primary peripheral blood mononuclear cells
      (PBMCs) cultures established from HIV-1-infected patients were treated with KP in
      comparison with zidovudine and supernatants and cells were harvested for analysis
      of HIV RNA and proviral contents, respectively. Virus production in exogenous in
      vitro PBMCs infection with lymphocytotropic and monocytotropic HIV-1 strains was
      also assessed in presence of KP by enzyme-linked immunosorbent assay HIV p24 gag
      antigen detection. The binding affinity of KP to CD4, CCR5 and CXCR4 was
      evaluated on CD4-CCR5 or CD4-CXCR4 transfected astroglioma cell lines. RESULTS:
      KP was shown to be devoid of cytotoxicity on PBMCs and to inhibit HIV-1
      replication in PBMCs of a patient in the acute phase of infection. The
      antiretroviral activity of KP, which proved to be more potent than zidovudine at
      micromolar concentrations, is abolished by beta 1,3-glucan but not by beta 1,6
      glucan. Down-regulation of CCR5 co-receptor, and/or physical block of the gp120
      receptor interaction are possible mechanisms of KP activity. CONCLUSION: KP
      appears to be the first antibody-derived short peptide displaying an inhibitory
      activity against HIV-1 and related opportunistic micro-organisms by different
      mechanisms of action.

PMID- 16603849
TI  - Reverse transcriptase mutations 118I, 208Y, and 215Y cause HIV-1
      hypersusceptibility to non-nucleoside reverse transcriptase inhibitors.
AB  - BACKGROUND: HIV-1 hypersusceptibility to non-nucleoside reverse transcriptase
      inhibitors (NNRTI) improves the response to NNRTI-containing regimens. The
      genetic basis for NNRTI hypersusceptibility was partly defined in our earlier
      analyses of a paired genotype-phenotype dataset of viral isolates from treatment
      experienced patients, in which we identified reverse transcriptase mutations
      V118I, H208Y, and T215Y as being strongly associated with NNRTI
      hypersusceptibility. OBJECTIVES: We evaluated the role of these mutations in
      NNRTI hypersusceptibility by site-directed mutagenesis and phenotypic analysis of
      HIV-1 recombinants. METHODS: Drug susceptibility and replication capacity were
      determined in single cycle assays. Hypersusceptibility was defined by a
      statistically significant (P < 0.01; Student's t-test) mean fold-change in 50%
      inhibitory concentration (IC50) of less than 0.4. RESULTS: The single mutations
      V118I, H208Y, and T215Y did not show hypersusceptibility to efavirenz with mean
      fold-change of 0.58, 0.55, and 0.70, respectively (P < 0.01 and P = 0.12). The
      H208Y/T215Y and V118I/H208Y/T215Y mutants showed marked hypersusceptibility to
      efavirenz, having mean fold-change values of 0.27 and 0.20, respectively (P <
      0.001). In addition, H208Y/T215Y, V118I/T215Y, and V118I/H208Y/T215Y were
      hypersusceptible to delavirdine and nevirapine. The V118I/T215Y mutant was not
      replication impaired; whereas H208Y/T215Y and V118I/H208Y/T215Y had significantly
      (P < 0.01) reduced replication capacities of 40 and 35% of wild-type,
      respectively. CONCLUSION: Different combinations of V118I, H208Y, and T215Y
      produce NNRTI hypersusceptibility. The V118I/T215Y mutant is hypersusceptible to
      delavirdine and nevirapine without reduced replication capacity, whereas the
      H208Y/T215Y and V118I/H208Y/T215Y mutants are hypersusceptible to all NNRTI and
      show impaired replication. These findings suggest that more than one mechanism is
      involved in NNRTI hypersusceptibility.

PMID- 16603850
TI  - Fluorodeoxyglucose imaging in healthy subjects with HIV infection: impact of
      disease stage and therapy on pattern of nodal activation.
AB  - OBJECTIVES: Nodal uptake in areas of lymphocyte activation can be visualized
      using fluorodeoxyglucose. Various patterns of fluorodeoxyglucose accumulation in
      HIV-positive patients have been described previously and hypothesized potentially
      to represent regions of active HIV replication or nodal activation. We evaluated
      the utility of fluorodeoxyglucose scanning as a tool to study HIV pathogenesis.
      DESIGN: We evaluated fluorodeoxyglucose biodistribution visually and
      quantitatively in HIV-negative individuals and various groups of HIV-infected
      patients to determine the impact on the pattern of nodal activation of HIV
      infection, the stage of HIV infection and degree of viremia, and HAART. In
      addition, we attempted to image anatomical site(s) of ongoing HIV replication in
      patients with suppressed HIV viremia on HAART, but subsequently discontinued
      HAART. METHOD: We performed fluorodeoxyglucose imaging on five groups: HIV
      negative, HIV-positive individuals with early infection, HIV-positive patients
      with advanced disease, HIV-positive patients with suppressed viral loads, and HIV
      positive patients who stopped HAART. RESULTS: Healthy HIV patients with
      suppressed viral loads and HIV-negative individuals had no or little
      fluorodeoxyglucose nodal accumulation or any other hypermetabolic areas, whereas
      viremic individuals with early and advanced HIV had increased fluorodeoxyglucose
      in the peripheral nodes, indicating that fluorodeoxyglucose potentially
      identifies areas of HIV replication. Fluorodeoxyglucose biodistribution was
      similar between early and advanced-stage disease. Four of five patients taken off
      HAART had negative baseline scans but developed nodal uptake and increases in
      viral loads. CONCLUSION: Abnormal fluorodeoxyglucose accumulation occurs in the
      nodes of individuals with detectable viral loads. Interruption of effective HAART
      results in the activation of previously quiescent nodal areas.

PMID- 16603851
TI  - Decay of K103N mutants in cellular DNA and plasma RNA after single-dose
      nevirapine to reduce mother-to-child HIV transmission.
AB  - OBJECTIVES: Single-dose nevirapine (sd-NVP) for prevention of mother-to-child HIV
      1 transmission is associated with selection of resistant viral variants,
      particularly the Lysine (K) to Asparagine (N) mutation at codon 103 (K103N) of
      reverse transcriptase. As this may influence subsequent treatment responses, a
      better understanding of the dynamics of decay and persistence of this variant is
      needed. DESIGN AND METHODS: We measured the frequency of K103N mutants among a
      cohort of HIV-1-infected pregnant women recruited at an out-patient clinic in
      Johannesburg, South Africa. Samples taken 6 weeks, 3, 7 and 12 months after
      delivery from 67 HIV-1-infected women who received sd-NVP during labor to prevent
      transmission were analyzed. Quantification of K103N mutants in maternal plasma
      viral RNA and cellular DNA was done using an allele-specific real-time polymerase
      chain reaction assay capable of detecting codons AAC and AAT if their frequency
      was > 0.002 of the total viral population. RESULTS: Using the allele-specific
      assay, 87.1% (27/31) of RNA samples and 52.3% (23/44) of DNA samples collected 6
      weeks after sd-NVP had detectable K103N variants. This declined to 65.4% (17/26),
      38.9% (14/36), and 11.3% (6/53) in RNA at 3, 7 and 12 months respectively, and to
      4.2% (2/48) in DNA at 12 months. CONCLUSIONS: K103N resistant variants were
      present in almost all women at 6 weeks post-sd-NVP but declined rapidly over
      time. Resistant variants were detected less frequently in cellular DNA with
      persistence in this compartment by 12 months post-sd-NVP among only a minority.

PMID- 16603852
TI  - Effect of pravastatin on body composition and markers of cardiovascular disease
      in HIV-infected men--a randomized, placebo-controlled study.
AB  - OBJECTIVES: To determine the effect of the 3-hydroxy-3-methylglutaryl coenzyme A
      reductase inhibitor, pravastatin, on markers of cardiovascular risk and
      lipodystrophy in HIV-infected, protease inhibitor (PI)-treated men with
      hypercholesterolaemia. METHODS: A randomized, placebo-controlled, 16-week study
      was carried out on 33 HIV-infected, hypercholesterolaemic men (fasting total
      cholesterol > 6.5 mmol/L) on PI-containing therapy. Patients commenced dietary
      assessment and advice at week 0 and were randomized to 12 weeks pravastatin (40
      mg each night) or placebo from week 4. The primary endpoint was the time-weighted
      change (TWAUC) in total cholesterol from week 0. Secondary endpoints included
      TWAUC cholesterol from week 4 (start of pravastatin), total and regional body
      fat, fasting lipids, glucose, insulin, and markers of cardiovascular risk.
      RESULTS: Of 33 men randomized (pravastatin n = 16, mean age 48 years), 31
      completed the study. Groups were matched for baseline cholesterol and body
      composition. Although there was no significant between-group difference in TWAUC
      cholesterol from week 0 (pravastatin -0.6 +/- 1.0 versus placebo -0.4 +/- 1.0
      mmol/L/week; P = 0.8), TWAUC cholesterol from week 4 decreased more in the
      pravastatin group (-0.8 +/- 1.0 versus -0.3 +/- 0.9 mmol/L/week; P = 0.04).
      Neither triglycerides nor dietary intake changed. Subcutaneous fat increased
      significantly with pravastatin (+0.72 +/- 1.55 versus +0.19 +/- 0.48 kg change in
      limb fat, P < 0.04; +5.2 +/- 8.7 versus -1.3 +/- 13.7 cm change in abdominal
      subcutaneous fat, P = 0.02). Apart from homocystine, which decreased in the
      pravastatin group, there were no significant differences in other cardiovascular,
      lipid or glucose parameters. CONCLUSIONS: Despite limited effects on cholesterol,
      12 weeks use of pravastatin 40 mg each night in HIV-infected men with
      hypercholesterolaemia resulted in significant increases in subcutaneous fat.

PMID- 16603853
TI  - Reconstitution of antimycobacterial immune responses in HIV-infected children
      receiving HAART.
AB  - OBJECTIVE: Recent epidemiological studies in adults suggest that HAART can
      prevent the development of tuberculosis in HIV-infected individuals, but the
      mechanisms are incompletely understood and no data exist in children. We
      investigated whether changes in mycobacterial-specific immune responses can be
      demonstrated in children after commencing antiretroviral therapy. DESIGN: We
      measured mycobacterial growth in vitro using a novel whole-blood assay employing
      reporter-gene tagged bacillus Calmette-Guerin (BCG) in a prospective cohort study
      in the tuberculosis-endemic environment of South Africa. Key cytokines were
      measured in supernatants collected from the whole-blood assay using cytometric
      bead array. PATIENTS: A cohort of 15 BCG-vaccinated HIV-infected children was
      evaluated prospectively for in-vitro antimycobacterial immune responses before
      and during the first year of HAART. All children had advanced HIV disease. Nine
      children completed all study timepoints. RESULTS: Before HAART, blood from
      children showed limited ability to restrict the growth of mycobacteria in the
      functional whole-blood assay. The introduction of HAART was followed by rapid and
      sustained reconstitution of specific antimycobacterial immune responses, measured
      as the decreased growth of mycobacteria. IFN-gamma levels in culture supernatants
      did not reflect this response; however, a decline in TNF-alpha was observed.
      CONCLUSION: This is the first study using a functional in-vitro assay to assess
      the effect of HAART on immune responses to mycobacteria in HIV-infected children.
      Our in-vitro data mirror the in-vivo observation of decreased susceptibility to
      tuberculosis in HIV-infected adults receiving antiretroviral agents. This model
      may be useful for further characterizing immune reconstitution after HAART.

PMID- 16603854
TI  - Antiretroviral medications associated with elevated blood pressure among patients
      receiving highly active antiretroviral therapy.
AB  - OBJECTIVE: To examine the effect of antiretroviral agents and clinical factors on
      the development of elevated blood pressure (BP). METHODS: Observational cohort
      study of patients initiating their first HAART regimen. We evaluated mean BP
      prior to HAART and while receiving HAART in relation to antiretroviral classes
      and individual agents, and demographic and clinical characteristics including
      change in body mass index (BMI) while on HAART. We used logistic regression
      analysis to examine factors associated with elevated BP [> or = 10 mmHg increase
      in systolic BP (SBP), diastolic BP (DBP) or new diagnosis of hypertension].
      RESULTS: Among 444 patients who had 4592 BP readings, 95 patients developed
      elevated SBP (n = 83), elevated DBP (n = 33), or a new diagnosis of hypertension
      (n = 11) after initiating HAART. In multivariate analysis, patients on
      lopinavir/ritonavir had the highest risk of developing elevated BP [odds ratio
      (OR), 2.5; P = 0.03] compared with efavirenz-based regimens. When change in BMI
      was added to the model, increased BMI was significantly associated with elevated
      BP (OR, 1.3; P = 0.02), and the association between lopinavir/ritonavir and
      elevated BP was no longer present. Compared with lopinavir/ritonavir-based
      regimens, patients receiving atazanavir (OR, 0.2; P = 0.03), efavirenz (OR, 0.4;
      P = 0.02), nelfinavir (OR, 0.3; P = 0.02), or indinavir (OR, 0.3; P = 0.01) had
      significantly lower odds of developing elevated BP. CONCLUSIONS: Treatment with
      lopinavir/ritonavir is significantly associated with elevated BP, an effect that
      appears to be mediated through an increase in BMI. Patients receiving atazanavir
      were least likely to develop elevated BP. The impact of antiretroviral
      medications on cardiovascular disease risk factors will increasingly influence
      treatment decisions.

PMID- 16603855
TI  - Direct measurement of in-vivo vaginal microbicide levels of PRO 2000 achieved in
      a human safety study.
AB  - OBJECTIVES: To directly measure the cervico-vaginal lavage (CVL) and plasma PRO
      2000 concentrations achieved by vaginal dosing. DESIGN: A sub-study of a
      prospective randomized, double-blind phase 1 trial of a candidate vaginal
      microbicide, PRO 2000 gel. METHODS: Thirty-six sexually abstinent women self
      administered 4% PRO 2000 gel, 0.5% PRO 2000 gel or placebo gel twice on day 0 and
      then once daily for a further 12 days. RESULTS: There was no evidence of systemic
      absorption of PRO 2000. PRO 2000 concentrations in CVL exceeded 25 microg/ml in
      all women in both the 4 and 0.5% groups at 2 h post-first dose, and in 10 of 12
      of the women in the 4% gel group compared with five of 12 of women in the 0.5%
      group at 12 h post-seventh dose. Single use of both 4 and 0.5% PRO 2000 gels was
      therefore associated with levels of PRO 2000 in CVL that would be capable of
      preventing HIV infection in vitro, although the 4% gel gave a greater margin of
      excess. Levels substantially in excess of the target concentration were present
      12 h after repeated dosing in twice as many 4% gel recipients compared with 0.5%
      gel recipients. CONCLUSIONS: Both PRO 2000 gel strengths provided satisfactory in
      vivo HIV inhibitory concentrations. However, our observations show that higher
      concentrations of PRO 2000 are likely to provide a greater margin of potential
      efficacy in the context of sexual intercourse provided safety issues are
      equivalent for differing concentrations of the agent.

PMID- 16603856
TI  - Marked HIV prevalence declines in higher educated young people: evidence from
      population-based surveys (1995-2003) in Zambia.
AB  - OBJECTIVES: Higher educational attainment has been associated with a greater risk
      of HIV infection in sub-Saharan Africa. We investigated change over time in HIV
      prevalence by educational attainment in the general population. METHODS: The data
      stem from serial population-based HIV surveys conducted in selected urban and
      rural communities in 1995 (n = 2989), 1999 (n = 3506) and 2003 (n = 4442).
      Analyses were stratified by residence, sex and age-group. Logistic regression was
      used to estimate age-adjusted odds ratio of HIV between low (< or = 4 school
      years) and higher education (> or = 8 years) for the rural population and between
      low (< or = 7 school years) and higher education (> or = 11 years) for the urban
      population. RESULTS: There was a universal shift towards reduced risk of HIV
      infection in groups with higher than lower education in both sexes among urban
      young people [odds ratio (OR), 0.20; 95% confidence interval (CI), 0.05-0.73] in
      men and (OR, 0.33; 95% CI, 0.15-0.72) in women. A similar pattern was observed in
      rural young men (OR, 0.17; 95% CI, 0.05-0.59) but was less prominent and not
      statistically significant in rural women. In age 25-49 years, higher educated
      urban men had reduced risk in 2003 (OR, 0.43; 95%CI, 0.26-0.72) but this was less
      prominent in women. CONCLUSIONS: The findings suggested a shift in the
      association between educational attainment and HIV infection between 1995 and
      2003. The most convincing sign was the risk reduction among more educated younger
      groups where most infections can be assumed to be recent. The changes in older
      groups are probably largely influenced by differential mortality rates. The
      stable risk among groups with lower education might also indicate limitations in
      past preventive efforts.

PMID- 16603857
TI  - Clinical safety of HIV lipopeptides used as vaccines in healthy volunteers and
      HIV-infected adults.
AB  - BACKGROUND: HIV-1 lipopeptides have been developed by the French National Agency
      for AIDS Research (ANRS) for use as candidate vaccine against HIV since 1994.
      Between 1996 and 2005, four different lipopeptide constructs were tested alone or
      in combination with recombinant canarypox HIV vaccines in 10 trials conducted in
      France. The aim of this study was to review clinical safety of HIV lipopeptides.
      METHODS: A meta-analysis based on individual subject data examined clinical
      safety data collected in eight preventive trials and two therapeutic trials
      enrolling 200 HIV-1-uninfected healthy volunteers and 48 HIV-1-infected patients.
      RESULTS: Of 248 trial participants, eight (3.2%) did not complete follow-up:
      seven among the 200 healthy volunteers, and one among the 48 HIV-1 infected
      patients. During the 354 person-years of follow-up, 860 lipopeptides injections
      were administered. Local reactions were common. However, in trials where
      lipopeptides were tested without adjuvant and appropriate diluents, none of the
      vaccinees experienced severe local response. Systemic reactions were generally
      mild and transient. No grade 4 reaction was reported; 18 subjects experienced
      grade 3 systemic events related to the vaccination, mainly asthenia, fever,
      headache and arthralgia. Multivariate analysis showed that female sex, number of
      injections and diluent (more reactions in 5% glucose alone than in combination
      with Tris-HCl buffer) significantly increased systemic reactions related to the
      vaccination. CONCLUSION: These data demonstrate that reactogenicity and systemic
      safety of HIV lipopeptides vaccine are acceptable both in healthy volunteers and
      HIV-infected adults.

PMID- 16603859
TI  - This is no time to stop use of nevarapine to prevent mother-to-child transmission
      of HIV.

PMID- 16603858
TI  - Herpes simplex virus infection in women in the WIHS: epidemiology and effect of
      antiretroviral therapy on clinical manifestations.
AB  - OBJECTIVE: To determine the prevalence of infection with herpes simplex virus
      types 1 (HSV-1) and 2 (HSV-2) among women with and at high risk for HIV
      infection, and to evaluate the effect of HAART on the recurrence of genital
      lesions. METHODS: We evaluated the epidemiology and clinical manifestations
      associated with HSV-1 and HSV-2 among 1796 HIV-infected and 476 HIV-uninfected
      women enrolled in a multisite cohort study. Serum antibodies to HSV-1 and HSV-2
      at baseline and self-reported history of genital herpes, reports of recent
      genital sores and presence of genital ulcers on examination, and use of HAART
      regimen at each study visit were analyzed. RESULTS: Reactivity to HSV-1 only and
      HSV-2 only was detected in 18% and 20% of HIV-infected, and in 28% and 18% of HIV
      uninfected participants respectively; 58% of HIV-infected women and 45% of HIV
      uninfected women were seropositive for both HSV types. Reactivity to HSV-2 was
      associated with increasing age, more male sexual partners, earlier sexual debut,
      African-American race, Latina ethnicity, less education and lower income. HIV
      uninfected women reported significantly fewer genital sores than HIV-infected
      women who had used HAART for at least 1 year and had optimal CD4 cell gain and
      viral suppression (adjusted odds ratio (OR), 0.19; 95% confidence interval (CI),
      0.13-0.28). CONCLUSION: Use of HAART and subsequent immune recovery does not
      completely eliminate the effect of HIV infection on genital lesions among women
      with concurrent HSV-2 infection.

PMID- 16603860
TI  - Statins in HIV-associated lipodystrophy and metabolic syndrome: is there a
      missing link?

PMID- 16603861
TI  - Of molecules, macaques and global AIDS.

PMID- 16603862
TI  - Progression to AIDS and death in the era of HAART.

PMID- 16603863
TI  - The genotypic inhibitory quotient and the (cumulative) number of mutations
      predict the response to lopinavir therapy.
AB  - For 95 protease inhibitor-experienced HIV-1-infected patients, the genotypic
      inhibitory quotient (GIQ; trough level/number of mutations) was calculated for
      lopinavir. Three different sets of mutations showed equal predictive value.
      However, the use of cumulative numbers of mutations for calculation of the GIQ
      showed significantly better association with the virological response.
      Furthermore, the predictive value of the GIQ was no different from that of the
      number of mutations alone.

PMID- 16603864
TI  - Prevalence of the HIV-1 protease mutation I47A in clinical practice and
      association with lopinavir resistance.
AB  - Mutation proI47A has recently been associated with lopinavir/ritonavir (LPV/r)
      resistance. Only four out of 1859 specimens (0.2%) sent for drug resistance
      testing (219 drug-naive and 1650 antiretroviral-experienced) showed I47A. All
      belonged to patients failing LPV/r. The prevalence among protease inhibitor
      experienced patients was 0.6%. Phenotypic testing showed that proI47A caused high
      level lopinavir resistance (> 100-fold) and cross-resistance to amprenavir,
      whereas it caused hypersusceptibility to saquinavir. ProI47A should thus be
      considered the primary lopinavir resistance mutation.

PMID- 16603865
TI  - Potential for HIV transmission through unsafe injections.
AB  - We tested for HIV in discarded needles and syringe washes from 191 HIV-infected
      patients receiving injections in rural Cameroon. HIV-1 RNA was amplified from 34
      of 103 intravenous injection syringes and two of 88 intramuscular injection
      syringes. All 36 strains were HIV-1 group M. The majority belonged to the
      circulating recombinant form CRF02 (IbNg). Our data support a role for unsafe
      injections in the spread of HIV-1 in Africa, in contrast to recent studies.

PMID- 16603866
TI  - No association between GB virus C infection and disease progression in HIV-2
      infected patients from the French ANRS HIV-2 cohort.
AB  - Out of 183 HIV-2-infected patients tested in the ANRS CO8 HIV-2 cohort, 69 were
      exposed to GB virus C (GBV-C), yielding a prevalence of 38% (95% CI 30.7, 45.2).
      There was no significant difference between the CD4 cell count and HIV-2-RNA
      plasma viral load in patients exposed and not exposed to GBV-C. After adjusting
      for age and CD4 cell count, co-infection with GBV-C was not associated with
      clinical progression (hazard ratio 0.78; 95% CI 0.24-2.56, 16 clinical events).

PMID- 16603867
TI  - Does cotrimoxazole taken by HIV-infected individuals reduce mortality among HIV
      uninfected family members? Data may not support conclusion.

PMID- 16603869
TI  - Exposure to HIV and antiretroviral medication as a potential cause of necrotizing
      enterocolitis in term neonates.

PMID- 16603870
TI  - Maintenance of successful ritonavir-boosted indinavir and efavirenz therapy in an
      HIV-infected patient with tuberculosis.

PMID- 16603871
TI  - Plasma and cerebrospinal pharmacokinetics and pharmacodynamics in subjects taking
      lopinavir/ritonavir.

PMID- 16603872
TI  - Critical drug interaction between ritonavir-boosted atazanavir regimen and non
      nucleoside reverse transcriptase inhibitors.

PMID- 16603873
TI  - Mesenteric panniculitis by cryptococcal infection in an HIV-infected man without
      severe immunosuppression.

PMID- 16603874
TI  - HIV prevention and treatment research in sub-Saharan Africa: where are the
      adolescents?

PMID- 16603875
TI  - Recognizing and challenging dogma.

PMID- 16603877
TI  - Consensus statement on injury definitions and data collection procedures in
      studies of football (soccer) injuries.
AB  - BACKGROUND: Variations in definitions and methodologies have created differences
      in the results and conclusions obtained from studies of football (soccer)
      injuries; this has made interstudy comparisons difficult. PROCEDURE: An Injury
      Consensus Group was established under the auspices of Federation Internationale
      de Football Association Medical Assessment and Research Centre. Using a nominal
      group consensus model approach, a working document that identified the key issues
      related to definitions, methodology, and implementation was discussed by members
      of the group during a 2-day meeting. After this meeting, iterative draft
      statements were prepared and circulated to the members of the group for comment
      before the final consensus statement was produced. RESULTS: Definitions of
      injury, recurrent injury, severity, and training and match exposures in football,
      together with criteria for classifying injuries in terms of location, type,
      diagnosis, and causation are proposed. Proforma for recording players' baseline
      information, injuries, and training and match exposures are presented.
      Recommendations are made on how the incidence of match and training injuries
      should be reported and a checklist of issues and information that should be
      included in published reports of studies of football injuries is presented.
      CONCLUSIONS: The definitions and methodology proposed in the consensus statement
      will ensure that consistent and comparable results will be obtained from studies
      of football injuries.

PMID- 16603878
TI  - Understanding the relationship between risks and odds ratios.
AB  - BACKGROUND: Many articles provide only odds ratios (OR) and non relative risks
      (RR) as the effect estimate. For a variety of important reasons, multiple
      logistic regression used to adjust for confounders routinely provides only the
      adjusted OR (ORadj). However, from the clinician's perspective, the ORadj is only
      easily interpretable when it approximates the adjusted RR (RRadj). In general,
      the relationship between the OR and RR (adjusted or nonadjusted) is dependent on
      prevalence of disease in the control group (Po) and has always been presented as
      nonlinear. Therefore, it is difficult for the clinician to convert the OR to RR
      when reading the published data. A formula was proposed by Zhang and Yu, but the
      relationship remains nonlinear. OBJECTIVE: To develop a simple method to convert
      OR to RR without the use of computer. METHODS: Algebraic manipulation. RESULTS:
      Through algebraic manipulation, we show that although the OR and RR relationship
      is nonlinear over the range Po, the ratio OR/RR has a linear relationship with Po
      with a slope of "OR-1": OR/RR=(OR-1)xPo+1. This makes the prediction of RR on the
      basis of OR more transparent. It is clear that if Po is small, the RR
      approximates the OR, but only if the OR is also small. Previous problems with
      confidence intervals noted with the Zhang and Yu formula remain (ie, they are too
      narrow under some conditions) and the result should be interpreted with this
      limitation. Relationships between ORadj and risk difference or number needed to
      treat remain curvilinear, but some overall approximations can be made.
      CONCLUSION: A simple relationship exists that allows readers to easily convert
      ORadj to RRadj. Limitations of the approach remain but seem to be less
      restrictive than the limitations of not converting ORadj to RRadj.

PMID- 16603879
TI  - Follow-up evaluation 2 years after ACL reconstruction with bone-patellar tendon
      bone graft shows that excessive tibial rotation persists.
AB  - OBJECTIVE: To investigate in vivo if the increased tibial rotation found in
      anterior cruciate ligament (ACL)-deficient patients before surgery is restored 2
      years after the reconstruction, during 2 high-demanding activities. DESIGN:
      Prospective follow-up study. SETTING: A gait analysis laboratory. PARTICIPANTS:
      Nine subjects with unilateral ACL rupture, reconstructed with a bone-patellar
      tendon-bone (BPTB) graft, and 10 healthy control subjects. INTERVENTIONS: All the
      ACL-deficient patients underwent a unilateral ACL reconstruction after
      prereconstruction data acquisition. MAIN OUTCOME MEASUREMENTS: Using a 6-camera
      motion analysis system, kinematics were collected as subjects (1) descended from
      a stair and, after foot contact, pivoted on the landing leg at 90 degrees; and
      (2) jumped from a platform, landed with both feet on the ground and, after foot
      contact, pivoted on the right or left leg at 90 degrees in a similar fashion. The
      dependent variable examined was the maximum range of motion of tibial rotation
      during the pivoting period. RESULTS: For both activities, no significant
      differences were found between the control healthy knee and the intact knee of
      the patient group before and 2 years after the ACL reconstruction. Significant
      differences were found between the control healthy knee and the affected knee of
      the patients group for both activities, both before and 2 years after the ACL
      reconstruction. CONCLUSION: The increased tibial rotation found in the ACL
      deficient knees was not restored with reconstruction using a BPTB graft, even 2
      years postoperatively. The authors propose that this excessive tibial rotation
      over time may lead to further deterioration of the knee resulting from abnormal
      loading at areas of the cartilage that are not commonly loaded in a healthy knee.

PMID- 16603880
TI  - Osteitis pubis and assessment of bone marrow edema at the pubic symphysis with
      MRI in an elite junior male soccer squad.
AB  - OBJECTIVES: To assess bone marrow edema at the pubic symphysis with magnetic
      resonance imaging (MRI), and its relation to training and osteitis pubis in an
      elite group of junior soccer players. SETTING: Soccer players on scholarship at
      the Australian Institute of Sport (AIS). PATIENTS: Nineteen players from an elite
      junior men's soccer squad. INTERVENTION/ASSESSMENT: Serial MRI examinations of
      the pubic symphysis over a 4-month training and playing period, training session
      questionnaire, and review of clinical diagnosis, investigations, and records on
      presentation of athletes with groin pain at the Department of Sports Medicine.
      MAIN OUTCOME MEASURES: Assessment of bone marrow edema (4-point scale) on MRI
      scans, review of athlete questionnaires, and review of clinical records. RESULTS:
      Initial MRI scans showed moderate to severe bone marrow edema at the pubic
      symphysis in 11 of the 18 asymptomatic players. There was a greatly decreased
      risk of developing groin pain (osteitis pubis) with more training prior to entry
      of the AIS soccer program (odds ratio per 4 sessions of training, 0.003). The
      correlation between initial bone marrow edema grading and pre-AIS training was
      small. The increase in bone marrow edema grading from baseline over the scans was
      0.5 (90% CL, 0.4). CONCLUSIONS: Substantial amounts of bone marrow edema at the
      pubic symphysis can occur in asymptomatic elite junior soccer players, but it is
      only weakly related to the development of osteitis pubis. Progressing training
      loads more slowly in athletes presenting with low current training loads may be a
      useful strategy for the prevention of osteitis pubis in junior soccer players.

PMID- 16603881
TI  - Surgery for chronic Achilles tendinopathy yields worse results in nonathletic
      patients.
AB  - OBJECTIVE: To report the outcome of surgery for chronic recalcitrant Achilles
      tendinopathy in nonathletic and athletic subjects. DESIGN: Case-control study.
      SETTING: University teaching hospitals. PATIENTS: We matched each of the 61
      nonathletic patients with a diagnosis of tendinopathy of the Achilles tendon with
      an athletic patient with tendinopathy of the main body of the Achilles tendon of
      the same sex and age (+/-2 years). A match was possible for 56 patients (23 males
      and 33 females). Forty-eight nonathletic subjects and 45 athletic subjects agreed
      to participate. INTERVENTIONS: Open surgery for Achilles tendinopathy. MAIN
      OUTCOME MEASURE: Outcome of surgery, return to sport, complication rate. RESULTS:
      Nonathletic patients were shorter and heavier than athletic patients. They had
      greater body mass index, calf circumference, side-to-side calf circumference
      differences, and subcutaneous body fat than athletic patients. Of the 48
      nonathletic patients, 9 underwent further surgery during the study period, and
      only 25 reported an excellent or good result. Of the 45 athletic subjects, 4
      underwent further surgery during the study period, and 36 reported an excellent
      or good result. The remaining patients could not return to their normal levels of
      activity. In all of them, pain significantly interfered with daily activities.
      CONCLUSIONS: Nonathletic subjects experience more prolonged recovery, more
      complications, and a greater risk of further surgery than athletic subjects with
      recalcitrant Achilles tendinopathy.

PMID- 16603882
TI  - Comparison of shock transmission and forearm electromyography between experienced
      and recreational tennis players during backhand strokes.
AB  - OBJECTIVE: To test the hypothesis that recreational tennis players transmit more
      shock impact from the racket to the elbow joint than experienced tennis players
      during the backhand stroke. Also, to test whether recreational tennis players
      used higher electromyographic (EMG) activities in common wrist extensor and
      flexor around epicondylar region at follow-through phase. DESIGN: A repeated
      measure, cross-sectional study. SETTING: National College of Physical Education
      and Sports at Taipei, Taiwan. PARTICIPANTS: Twenty-four male tennis players with
      no abnormal forearm musculoskeletal injury participated in the study. According
      to performance level, subjects were categorized into 2 groups: experienced and
      recreational. MAIN OUTCOME MEASUREMENTS: Impact transmission and wrist extensor
      flexor EMG for backhand acceleration, impact, and follow-through phases were
      recorded for each player. An independent t test with a significance level of 0.05
      was used to examine mean differences of shock impact and EMG between the 2 test
      groups. One-way ANOVA associated with Tukey multiple comparisons was used to
      identify differences among different impact locations and EMG phases. RESULTS:
      Experienced athletes reduced the racket impact to the elbow joint by 89.2%, but
      recreational players reduced it by only 61.8%. The largest EMG differences were
      found in the follow-through phase (P<0.05). Experienced athletes showed that
      their extensor and flexor EMGs were at submaximal level for follow-through phase,
      whereas recreational players maintained their flexor and extensor EMGs at either
      supramaximal or maximal level. CONCLUSIONS: Our results support the hypothesis
      that recreational players transmit more shock impact from the racket to the elbow
      joint and use larger wrist flexor and extensor EMG activities at follow-through
      phase of the backhand stroke. Follow-through control is proposed as a critical
      factor for reduction of shock transmission. Clinicians or trainers should
      instruct beginners to quickly release their grip tightness after ball-to-racket
      impact to reduce shock impact transmission to the wrist and elbow.

PMID- 16603883
TI  - Sports-related injuries in the United States: who gets care and who does not.
AB  - OBJECTIVE: To describe the pattern of sports-related injuries (SRIs), healthcare
      obtained for these injuries, and factors associated with obtaining healthcare.
      DESIGN AND SETTING: Retrospective analysis of the adult subgroup within the
      Medical Expenditures Panel Survey dataset from 1996 to 2001, which is weighted to
      represent all noninstitutionalized US residents. PARTICIPANTS: Survey
      participants (2996) aged 0 to 64 years reporting an SRI. MAIN OUTCOME
      MEASUREMENT: Whether healthcare was obtained for an SRI. RESULTS: A weighted
      estimate of 6.7 million individuals reported an SRI annually. Two million
      individuals (30%) did not obtain healthcare for an SRI. Twenty-four percent of
      those with "serious" injuries did not obtain healthcare. Predictors of obtaining
      healthcare include the following: an upper extremity injury [adjusted odds ratio
      (OR) 1.57, 95% confidence intervals (CI): 1.17, 2.10]; a "very or somewhat
      serious" injury (adjusted OR 1.64, 95% CI 1.24, 2.17); and one SRI versus >1 SRI
      (adjusted OR 1.37, 95% CI: 1.06, 1.78). Predictors of not obtaining healthcare
      for an SRI include the following: Black race (adjusted OR 0.59, 95%CI: 0.44,
      0.79); no health insurance (adjusted OR 0.45, 95%CI: 0.33, 0.63); and no usual
      source of care (adjusted OR 0.71, 95% CI: 0.56, 0.91). CONCLUSIONS: SRIs are
      common and often patients do not obtain healthcare for these injuries. Among
      Americans with an SRI, those who are Black, and those who lack insurance or a
      usual source of care, are at risk for not obtaining care for an SRI. Not
      obtaining healthcare and lacking knowledge about the consequences of sports
      injury may lead to unnecessary, additional morbidity and cost. Education targeted
      at these groups, at their physicians, and at policymakers may help reduce
      untreated SRIs.

PMID- 16603884
TI  - Health of master track and field athletes: a 16-year follow-up study.
AB  - OBJECTIVE: To study different aspects of health in master athletes. DESIGN: A 16
      year follow-up study. SETTING: Finland. PARTICIPANTS: All male Finnish master
      athletes (N=102, mean age 58.3 years) who in 1985 participated in track and field
      athletic World Veterans Games. Controls were men, who as young adults had been
      classified as completely healthy (N=777, mean age 55.0 years). MAIN OUTCOME
      MEASUREMENTS: Health questionnaires at baseline (in 1985) and at 10-year and 16
      year follow-ups. RESULTS: During follow-up, the master athletes self-rated their
      health as better (P<0.001) and they coped better with leisure-time daily
      activities (P=0.024) than controls. The adjusted risk for shoulder region (odds
      ratio 2.84, P<0.03) and Achilles tendon rupture (14.87, P<0.01) after the age of
      45 years was higher in the athletes than in the controls. At the 16-year follow
      up, none of the athletes, but 9% of controls reported having diabetes mellitus.
      The adjusted odds ratio of having at least 1 metabolic syndrome disease was 0.43
      (P=0.01) in the athletes compared with the controls. At follow-up among subjects
      without reported coronary heart disease in 1985, the age-adjusted hazard ratio
      (HR) in the athletes compared with the controls of death from natural-cause was
      0.41 (P<0.01). CONCLUSIONS: Master athletes had a lower risk of chronic diseases
      than the controls. It remains to be determined how far this advantage is due to
      initial selection and/or incomplete adjustment for covariates. CLINICAL
      RELEVANCE: There seems to be no such health risks as to why those who have good
      training background and feel healthy should avoid participating in master
      athletics.

PMID- 16603885
TI  - Musculoskeletal injury in the masters runners.
AB  - OBJECTIVE: To determine if injury patterns and risk factors for injury differ
      between masters and younger runners. DESIGN: Retrospective survey. SETTING: Hood
      to Coast running relay, Oregon, USA. PARTICIPANTS: A total of 2886 runners
      consented to participate and completed the survey. Ninety-four (2712/2886)
      percent completed the survey electronically and 6% (174/2886) manually. Master
      runners (>or=40 years) made up 34% of the population. INTERVENTION: The survey
      was distributed to all participants in the largest running relay in North
      America. Runners reported on training patterns, injury location, and diagnosis
      over the previous year. MAIN OUTCOME MEASURES: Descriptive statistics and chi
      analysis were used to detect differences in injury rate and location between
      masters and younger runners. Multivariate logistic regression models were used to
      identify risk factors for injury for each group. RESULTS: The injury rate for the
      entire population was 46%. Significantly more masters runners were injured than
      younger runners (P<0.05). More masters runners suffered multiple injuries than
      younger runners (P<0.001). Significantly more masters runners were male, had 7 or
      more years of running experience, run more than 30 miles/wk, 6 or more times/week
      and wear orthotics than younger runners (P<0.001). The knee and foot were the
      most common locations of injury for both groups. The prevalence of soft-tissue
      type injuries to the calf, achilles, and hamstrings was greater in masters
      runners than their younger counterparts (P<0.001). Younger runners suffered more
      knee and leg injuries than masters runners (P<0.005). Running more times/wk
      increased the risk of injury for both groups. CONCLUSIONS: There were subtle
      differences in injury rate and location between masters runners and younger
      runners, which may reflect differences in training intensity.

PMID- 16603886
TI  - Intratester and intertester reliability of clinical measures of lower extremity
      anatomic characteristics: implications for multicenter studies.
AB  - OBJECTIVE: To determine whether multiple examiners could be trained to measure
      lower extremity anatomic characteristics with acceptable reliability and
      precision, both within (intratester) and between (intertester) testers. We also
      determined whether testers trained 18 months apart could perform these
      measurements with good agreement. SETTING: University's Applied Neuromechanics
      Research Laboratory. PARTICIPANTS: Sixteen, healthy participants (7 men, 9
      women). ASSESSMENT OF RISK FACTORS: Six investigators measured 12 anatomic
      characteristics on the right lower extremity in the Fall of 2004. Four testers
      underwent training immediately preceding the study, and measured subjects on 2
      separate days to examine intratester reliability. Two testers trained 18 months
      before the study (Spring 2002) measured each subject on day 1 to examine the
      consistency of intertester reliability when testers are trained at different
      times. MAIN OUTCOME MEASUREMENTS: Knee laxity, genu recurvatum, quadriceps angle,
      tibial torsion, tibiofemoral angle, hamstring extensibility, pelvic angle,
      navicular drop, femur length, tibial length, and hip anteversion. RESULTS: With
      few exceptions, all testers consistently measured each variable between test days
      (intraclass correlation coefficient>or=0.80). Intraclass correlation coefficient
      values were lower for intertester reliability (0.48 to 0.97), and improved from
      day 1 to day 2. Intertester reliability was similar when comparing testers
      trained 18 months before those trained immediately before the study. Absolute
      measurement error varied considerably across individual testers. CONCLUSIONS:
      Multiple investigators can be trained at different times to measure anatomic
      characteristics with good to excellent intratester reliability. Intratester
      reliability did not always ensure acceptable intertester reliability or
      measurement precision, suggesting more training (or more experience) may be
      required to achieve acceptable measurement reliability and precision between
      multiple testers.

PMID- 16603887
TI  - Mechanisms of injury for concussions in university football, ice hockey, and
      soccer: a pilot study.
AB  - OBJECTIVE: To examine the mechanisms of injury for concussions in university
      football, ice hockey, and soccer. DESIGN: Prospective analysis. SETTING: McGill
      University. PATIENTS: All athletes participating in varsity football, ice hockey,
      and soccer. MAIN OUTCOME MEASURES: Athletes participating in university varsity
      football, ice hockey, and soccer were followed prospectively to determine the
      mechanisms of injury for concussions, whether certain mechanisms of injury
      causing concussions were more common in any of the three sports, whether
      different areas of the body seem to be more vulnerable to a concussion after
      contact, and whether these areas might be predisposed to higher grades of
      concussion after contact. RESULTS: There were 69 concussions in 60 athletes over
      a 3-year period. Being hit in the head or helmet was the most common mechanism of
      injury for all 3 sports. The side/temporal area of the head or helmet was the
      most probable area to be struck, resulting in concussion for both football and
      soccer. When examining the body part or object delivering the concussive blow,
      contact with another player's helmet was the most probable mechanism in football.
      CONCLUSION: The mechanisms of injury for concussions in football are similar to
      previously published research on professional football players. The mechanisms of
      injury for concussions in soccer are similar to past research on Australian rules
      football and rugby.

PMID- 16603888
TI  - A new self-diagnostic test for biceps femoris muscle strains.
AB  - OBJECTIVE: We compared a self-performed diagnostic test that we have been using
      since 1987, with other commonly used clinical tests for biceps femoris muscle
      strain injuries. SETTING: Private practice focusing on sports injuries. PATIENTS:
      One-hundred forty professional male soccer players (ages 17 to 33 years) with a
      history and clinical findings of a pulled hamstring muscle (patients with direct
      trauma were excluded) had an ultrasound-proven grade I or II biceps femoris
      muscle injury. INTERVENTIONS: In these ultrasound-positive patients, the "taking
      off the shoe" test (TOST) was performed by the patient himself on both the
      affected and unaffected legs; and the physician then performed the resisted range
      of motion, passive range of motion, and active range of motion tests. RESULTS:
      The TOST had a sensitivity and specificity of 100%, and a positive predictive
      value and an negative predictive value of 100% for biceps femoris injury as found
      on ultrasound. The other muscle tests had an average sensitivity of 57%,
      specificity of 100%, accuracy of 79%, and negative predictive value of 70%.
      CONCLUSION: This preliminary, nonblinded observational study of the TOST found it
      to be more reliable than other commonly used clinical tests for hamstring tears.
      The clinical value of this easy-to-perform test should be evaluated in a
      prospective fashion.

PMID- 16603889
TI  - Practical management: nonsteroidal antiinflammatory drug (NSAID) use in athletic
      injuries.
AB  - Nonsteroidal antiinflammatory drugs (NSAIDs) are frequently used in the treatment
      of acute athletic injuries, often for analgesic purposes as the evidence to
      support enhanced healing is limited. However, the current evidence on NSAID use
      in athletic injury is slowly growing. On the basis of animal models and limited
      human studies, some practical management guidelines can be drawn to assist the
      sports physician. Specifically, NSAIDs are not recommended in the treatment of
      completed fractures, stress fractures at higher risk of nonunion, or in the
      setting of chronic muscle injury. The only exception may be very short-term use
      (eg, a few days) for analgesic purposes only. Judicious use of NSAIDs may be more
      appropriate in the management of acute ligament sprains, muscle strains,
      tendinitis, and eccentric muscle injury. However, length of treatment should
      always be kept as short as possible, with consideration of the specific type of
      injury, level of dysfunction, and pain.

PMID- 16603890
TI  - Groin pain in athletes: a consequence of femoral head avascular necrosis after
      testicular cancer chemotherapy.

PMID- 16603891
TI  - Pulmonary contusion in football players.

PMID- 16603892
TI  - Traumatic mydriasis: "cat's eye" in a football player.

PMID- 16603893
TI  - Drugs and competitive sports.

PMID- 16603894
TI  - Exercise therapy for nonspecific low-back pain: a meta-analysis.

PMID- 16603895
TI  - Abstracts of the 4th International Meeting on Inflammatory Bowel Diseases. On the
      Way to New Therapies. April 9-12, 2006, Capri, Italy.

PMID- 16603899
TI  - The first 18 months in practice: a developmental transition model for the newly
      graduated nurse.
AB  - The purpose of this article is to present a process model of the development of a
      newly graduated nurse. The model is useful in helping new graduates interpret
      their experience during their first crucial months in practice and can be used by
      organizations to design developmentally appropriate support strategies. The model
      integrates novice to expert skill acquisition, adult learning, and transition
      theory.

PMID- 16603901
TI  - Nurse residency programs: Redesigning the transition into practice.
AB  - Two Wisconsin healthcare systems created a common definition and identified the
      essential components for a model nurse residency program (NRP). This community
      learning design was based on action learning principles. The results demonstrated
      improved retention, critical thinking, socialization, ability to manage stress,
      and problem-solving skills in new graduate nurses. The findings suggest that
      significant redesign of traditional learning methodology is required to achieve
      desired goals.

PMID- 16603903
TI  - Evaluating your educational plan: Are you meeting the needs of nurses?
AB  - The authors discuss a descriptive educational needs assessment survey based on
      Benner's Skill Acquisition Model to determine staff nurses' perception of
      quantity and relevance of educational programs offered to nurses. The evaluations
      of the feedback received, such as lack of knowledge of available educational
      offerings and the need to expand the current curriculum, are presented. The main
      assumption that course offerings have changed or validated practice was
      supported. Changes based on the information obtained by the survey participants
      involve expansion of the curriculum using a case study approach.

PMID- 16603904
TI  - Effects of a 1-year residency program on job satisfaction and retention of new
      graduate nurses.
AB  - Residency programs, first reported in the literature in the 1980s, are of
      documented value for the successful training of a graduate nurse into practice.
      With the present nursing shortage, residency programs are regarded as an
      important feature in attracting and retaining the much needed new graduate. Six
      university hospitals pilot tested a residency program to ease new graduate
      transition into practice. The purpose of this study was to ascertain if a
      yearlong program results in increased levels of satisfaction in and retention of
      new graduates.

PMID- 16603905
TI  - Clinical educators' empowerment, job tension, and job satisfaction: A test of
      Kanter's Theory.
AB  - Recruitment and retention of qualified nursing staff are vital to safe patient
      care and require the expertise of clinical educators to facilitate the nurses'
      professional development. However, organizational redesign has challenged
      clinical educators with role ambiguity, job stress, and decreased job
      satisfaction. This study used Kanter's Structural Theory of Organizational
      Behavior to examine the relationships between clinical educators' perceptions of
      empowerment, job tension, and job satisfaction. High levels of workplace
      empowerment were significantly related to low levels of job tension. In addition,
      the combination of high levels of empowerment and low levels of job tension was
      predictive of high levels of job satisfaction. Implications for staff development
      administrators are discussed.

PMID- 16603906
TI  - Developing and using online courses to prepare nurses for employment in critical
      care.
AB  - Using online courses is one way to simplify orientation programs and leverage
      educator resources. Three critical care courses were created using a distributed
      authoring model with geographically diverse clinical experts. A companion online
      orientation course prepares preceptors to assist with clinical application.
      Course outcomes include preparation for practice, career mobility/advancement,
      and learner satisfaction.

PMID- 16603907
TI  - Administration.

PMID- 16603908
TI  - Instant teaching tools.

PMID- 16603909
TI  - Preceptorship.

PMID- 16603911
TI  - Enriched acoustic environment after noise trauma abolishes neural signs of
      tinnitus.
AB  - Noise-induced hearing loss induces reorganization of the tonotopic map in cat
      auditory cortex and increases spontaneous firing rate and neural synchrony. We
      showed previously that keeping cats after noise trauma in an acoustic environment
      enriched in high frequencies prevents tonotopic map reorganization. Here, we show
      the effects of low-frequency and high-frequency enriched acoustic environments on
      spontaneous firing rate and neural synchrony. Exposed cats placed in the quiet
      environment and in the low-frequency enriched acoustic environment showed
      increased spontaneous firing rate and synchrony of firing. In contrast, exposed
      cats placed in the high-frequency enriched acoustic environment did not show
      significant differences in spontaneous firing rate or synchrony compared with
      normal hearing controls. This is interpreted as an absence of putative neural
      signs of tinnitus.

PMID- 16603912
TI  - Temporal characteristics of visual receptive fields in primary visual cortex and
      medial superior temporal cortex areas.
AB  - We mapped the receptive fields of 49 cells from primary visual cortex and 19
      cells from medial superior temporal cortex in two awake monkeys. The receptive
      field structures we obtained lasted a mean time of 32.7 ms in primary visual
      cortex and 38.4 ms in medial superior temporal cortex, showing no statistical
      difference. This result suggests that both areas have the same time requirements
      for processing visual information. In primary visual cortex, 100% of cells had
      conformed the receptive field structure at 65 ms pre-spike, whereas in medial
      superior temporal cortex it occurred at 150 ms. In both areas, cells with shorter
      response latencies had receptive field structures with longer durations. This may
      indicate that cells tend to synchronize their output to other areas.

PMID- 16603913
TI  - Neurogenesis in the adult rat piriform cortex.
AB  - Multipotent neural precursors have been suggested to exist in many parts of the
      adult mammalian brain. In the present study, we characterized the neurogenic
      potential in the piriform cortex of adult rats. Proliferation rates as detected
      by 5'-bromodeoxyuridine-labeling proved to be low when compared with the major
      neurogenic brain regions (i.e. the hippocampus and the subventricular zone). 5'
      Bromodeoxyuridine/NeuN-labeling in accordance with doublecortin, polysialylated
      neural cell adhesion molecule, and TUC-4-labeling indicated that neuronal
      differentiation of newborn cells occurs predominantly in layer II of the piriform
      cortex. Many of the cells exhibited a pyramidal cell morphology. The lack of 5'
      bromodeoxyuridine/NeuN-labeled cells 12 weeks after 5'-bromodeoxyuridine
      administration argued against long-term survival of newborn neurons in the
      piriform cortex.

PMID- 16603914
TI  - Calcium-binding proteins in GABAergic calyciform synapses of the reticular
      nucleus.
AB  - Large calyciform synapses in the rat reticular thalamic nucleus are characterized
      by the presence of gamma-aminobutyric acid. Presynaptic terminals are also loaded
      with calcium-binding proteins such as parvalbumin, calbindin, calretinin and
      calcineurin. The number of calyciform terminals containing gamma-aminobutyric
      acid and parvalbumin is 2005 in young adult rats; calbindin is present in 1,500,
      calretinin in 850 and calcineurin in 560 calyciform terminals. Developmental
      studies revealed that gamma-aminobutyric acid and calcium-binding proteins are
      virtually absent from calyciform terminals at birth but their occurrence
      increased considerably during postnatal life, suggesting increasing regulation of
      presynaptic calcium signaling during postnatal life. It is concluded that
      synaptic activity of large calyciform gamma-aminobutyric acid-containing synapses
      of the reticular thalamic nucleus is mediated, regulated or accompanied by
      calcium ions.

PMID- 16603915
TI  - Head motion during overt language production in functional magnetic resonance
      imaging.
AB  - Head motion parameters (translation, rotation) during an event-related functional
      magnetic resonance imaging experiment of overt picture naming were investigated
      for two fixation conditions. We compared normal fixation with cushions and belts
      with the additional use of a bite-bar. Neither mean nor maximum values differed
      between the two conditions for any of the parameters. By applying the head motion
      parameters to the cytoarchitectonically defined volume of the left Brodmann area
      44, we demonstrated volume overlap of 95% (normal fixation) to 100% (bite-bar)
      that did not differ significantly between fixation conditions. The data encourage
      further use of overt language production in functional magnetic resonance imaging
      with careful head fixation but no bite-bar.

PMID- 16603916
TI  - Non-conscious recognition of emotional body language.
AB  - Patients with cortical blindness can reliably perceive some facial expressions
      even if they are unaware of their percept. We examined whether emotional body
      language may also be recognized in the absence of the primary visual cortex and
      without conscious stimulus perception. We presented emotional and neutral body
      images in the blind field of a patient with unilateral striate cortex damage.
      Using functional magnetic resonance imaging, we measured activation following
      presentation to the blind hemifield of whole body images (happy, neutral) with
      the face blurred. Unseen happy body images selectively activated area MT and the
      pulvinar nucleus of the thalamus, while unseen instrumental neutral body images
      activated the premotor cortex. Our results show that in the absence of the
      striate cortex implicit bodily emotion perception may be possible.

PMID- 16603917
TI  - Neural correlates of the number-size interference task in children.
AB  - In this functional magnetic resonance imaging study, 17 children were asked to
      make numerical and physical magnitude classifications while ignoring the other
      stimulus dimension (number-size interference task). Digit pairs were either
      incongruent (3 8) or neutral (3 8). Generally, numerical magnitude interferes
      with font size (congruity effect). Moreover, relative to numerically adjacent
      digits far ones yield quicker responses (distance effect). Behaviourally, robust
      distance and congruity effects were observed in both tasks. Imaging baseline
      contrasts revealed activations in frontal, parietal, occipital and cerebellar
      areas bilaterally. Different from results usually reported for adults, smaller
      distances activated frontal, but not (intra-)parietal areas in children.
      Congruity effects became significant only in physical comparisons. Thus, even
      with comparable behavioural performance, cerebral activation patterns may differ
      substantially between children and adults.

PMID- 16603918
TI  - Behavioral control of the stressor modulates stress-induced changes in
      neurogenesis and fibroblast growth factor-2.
AB  - The controllability of stressors modulates many of the consequences of stressor
      exposure. Here, we used immunohistochemistry to examine neural progenitor cell
      proliferation and survival and basic fibroblast growth factor-2 in the
      hippocampus of male rats after controllable or uncontrollable tailshock. A series
      of identical tailshocks were delivered to yoked pairs of rats. One rat could
      terminate shocks to both rats of the pair. Reductions in neural progenitor cells
      were observed at 1-2 days and at 28 days in rats exposed to uncontrollable shock.
      Controllable shock produced an increase in fibroblast growth factor-2 in the
      dentate gyrus and CA1 2 h after stress and in the dentate gyrus 24 h after
      stress. Thus, stressor controllability modulates stress-induced decreases in
      neurogenesis and increases in fibroblast growth factor-2.

PMID- 16603919
TI  - 18F-fluorodeoxyglucose hypometabolism in cerebellar tonsil and flocculus in
      downbeat nystagmus.
AB  - A patient with downbeat nystagmus was examined by F-fluorodeoxyglucose-positron
      emission tomography once while off and twice while on successful treatment with 4
      aminopyridine. All positron emission tomography scans of the patient showed a
      reduced cerebral glucose metabolism bilaterally in the region of the cerebellar
      tonsil and flocculus/paraflocculus when compared with a normal database of the
      whole brain. An additional region-of-interest analysis revealed that 4
      aminopyridine treatment lessened the hypometabolism. This finding supports the
      hypothesis that the cerebellar tonsil and (para-) flocculus play a crucial role
      in downbeat nystagmus. The hypometabolism might reflect reduced inhibition or
      even disinhibition of the circuits to the vestibular nuclei, thus causing
      downbeat nystagmus. The reduced hypometabolism during treatment probably
      indicates an improvement of the cerebellar inhibition.

PMID- 16603920
TI  - Nogo-66 receptor at the gap junctions between pituicytes of the rat.
AB  - Nogo-66 receptor was first identified in neurons. Recently, it was demonstrated
      in glial cells as well. Our previous study on the expression of Nogo-66 receptor
      in the cerebellum of the rat surprisingly found its location at the glial gap
      junctions. Here, we present our study on Nogo-66 receptor in the rat posterior
      pituitary, which is densely packed with pituicytes, a special type of astrocyte,
      and is known to be rich in gap junctions. We were able to demonstrate with
      immunohistochemistry and immuno-electron microscopy abundant Nogo-66 receptor
      immunoreactive gap junctions between pituicytes. This study, together with our
      prior one, strongly suggests that the Nogo-66 receptor may play a role in
      regulating the function of the gap junctions.

PMID- 16603921
TI  - A clinical test of otolith function: static ocular counterroll with passive head
      tilt.
AB  - When roll-tilted around the naso-occipital axis, humans exhibit compensatory
      torsional rotation of the eyes in the opposite direction owing to the torsional
      vestibulo-ocular reflex. In the static condition (sustained head roll), the
      utricles act as responsible sensors for 'static ocular counterroll'.
      Contributions of cervico-ocular reflexes remain unknown. To find an easy,
      clinically useful test of utricular function, we induced ocular counterroll in 10
      healthy study participants (two men, mean age 27+/-2 years) under three
      stimulation conditions (active/passive head tilt and passive whole body tilt in
      roll plane), used three-dimensional video-oculography to measure it, and compared
      values. Active head-tilt-induced ocular counterroll varied most and was thus less
      reliable than passive head and body tilt-induced ocular counterroll. Utricular
      function can thus be tested simply by measuring passive head tilt with video
      oculography.

PMID- 16603922
TI  - Frontal cortex functional connectivity changes during sound categorization.
AB  - Using functional connectivity analysis of functional magnetic resonance imaging
      data, we investigated the role of the inferior frontal gyrus in categorization of
      simple sounds. We found stronger functional connectivity between left inferior
      frontal gyrus and auditory processing areas in the temporal cortex during
      categorization of speech (vowels, syllables) and nonspeech (tones, combinations
      of tones and sweeps) sounds relative to an auditory discrimination task; the
      hemispheric lateralization varied depending on the speech-like properties of the
      sounds. Our results attest to the importance of interactions between temporal
      cortex and left inferior frontal gyrus in sound categorization. Further, we found
      different functional connectivity patterns between left inferior frontal gyrus
      and other brain regions implicated in categorization of syllables compared with
      other stimuli, reflecting the greater facility for categorization of syllables.

PMID- 16603923
TI  - Central nervous system stem/progenitor cells form neurons and peripheral glia
      after transplantation to the dorsal root ganglion.
AB  - We asked whether neural stem/progenitor cells from the cerebral cortex of E14.5
      enhanced green fluorescent protein transgenic mice are able to survive grafting
      and differentiate in the adult rat dorsal root ganglion. Neurospheres were placed
      in lumbar dorsal root ganglion cavities after removal of the dorsal root ganglia.
      Alternatively, dissociated neurospheres were injected into intact dorsal root
      ganglia. Enhanced green fluorescent protein-positive cells in the dorsal root
      ganglion cavity were located in clusters and expressed beta-III-tubulin or glial
      fibrillary acidic protein after 1 month, whereas after 3 months, surviving
      grafted cells expressed only glial fibrillary acidic protein. In the intact adult
      DRG, transplanted neural stem/progenitor cells surrounded dorsal root ganglion
      cells and fibers, and expressed glial but not neuronal markers. These findings
      show that central nervous system stem/progenitor cells can survive and
      differentiate into neurons and peripheral glia after xenotransplantation to the
      adult dorsal root ganglion.

PMID- 16603924
TI  - Estrogen counteracts ozone-induced oxidative stress and nigral neuronal death.
AB  - Oxidative stress is implicated in the premature death of dopamine neurons in
      substantia nigra in Parkinson's disease. The incidence of Parkinson's disease is
      higher in men than in women, and estrogen may provide neuroprotection against
      oxidative damage. We examined the protective effects of estrogen on rat nigral
      death after chronic ozone inhalation. Ozone inhalation produced impaired nigral
      cell morphology and loss of dopamine neurons in ovariectomized rats. This was
      counteracted after 60 days of 17beta-estradiol treatment, when blood levels were
      highest. These results indicate that ozone exposure may be a useful Parkinson's
      disease model and neuroprotection afforded by 17beta-estradiol is dependent on
      the high levels achieved after its prolonged administration.

PMID- 16603925
TI  - Low-frequency hearing loss in prenatally stressed rats.
AB  - We investigated the possibility that hearing thresholds are altered in prenatally
      stressed rats raised in a normal auditory environment. Pregnant dams were
      assigned randomly to prenatally stressed and control groups. Half of the dams
      were subjected to the mild stressors of handling, exposure to a novel cage and
      saline injection at random times during lights-on daily. The hearing thresholds
      of young adult male offspring were assessed by recording auditory-evoked
      brainstem responses to 0.5, 1, 2, 4, 8, 16, 32 and 64 kHz pure tones. The
      resultant audiograms showed that prenatally stressed offspring had significantly
      higher hearing thresholds than control animals at 1, 2 and 4 kHz (t-tests,
      P<0.05). The threshold shifts caused by prenatal stress averaged 7.7 dB across
      frequencies. We conclude that prenatal stress causes low-frequency hearing loss,
      possibly due to increased vulnerability to noise-induced hearing loss,
      accelerated cochlear degeneration and/or disrupted cochlear development.

PMID- 16603926
TI  - Pedunculopontine nucleus electric stimulation alleviates akinesia independently
      of dopaminergic mechanisms.
AB  - The symptom of Parkinson's disease that is most disabling and difficult to treat
      is akinesia. We have previously shown that low-frequency stimulation of the
      pedunculopontine nucleus can alleviate such akinesia in a macaque rendered
      Parkinsonian using 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine. Here, we have
      extended that study to show that adding stimulation of the pedunculopontine
      nucleus to levodopa treatment in this Parkinsonian monkey increased its motor
      activity significantly more than levodopa alone. This additivity suggests that
      pedunculopontine nucleus stimulation may improve movement by acting at a site
      downstream from where levodopa therapy affects the basal ganglia.

PMID- 16603927
TI  - Attending to depth: electrophysiological evidence for a viewer-centered
      asymmetry.
AB  - It has been proposed that the configuration of visuospatial attention in depth is
      viewer-centered such that an attentional gradient is concentrated between an
      observer and attended depth, trailing off steeply beyond. To investigate this
      asymmetry, event-related potentials were recorded while participants attended to
      far or near depths in a pictorial scene. The attention-sensitive visual
      components, P1 (100-160 ms) and N1 (160-220 ms), were assessed for amplitude
      differences. Amplitude enhancement of the P1 component was present when
      participants attended far but not near depths. Reaction time facilitation also
      followed this pattern. Results are consistent with a viewer-centered asymmetry
      because such a configuration predicts the gradient of attention to distribute
      differentially to far depths but to remain constant for near depths.

PMID- 16603928
TI  - Chronic hypoxia inhibits Na+/Ca2+ exchanger expression in cortical astrocytes.
AB  - Ca signalling is central to many diverse functions of astrocytes. Of the numerous
      proteins involved in Ca homeostasis, the Na(+)/Ca(2+) exchanger is of particular
      importance in signalling regulation. We have shown that Ca signaling is
      dramatically remodelled in astrocytes by periods of chronic hypoxia, in part by
      inhibition of Na(+)/Ca(2+) exchanger. Here, we demonstrate that bepridil
      sensitive Ca extrusion (indicative of Na(+)/Ca(2+) exchanger activity) is
      suppressed following 24 h hypoxia (2.5 or 1% O2) owing to a loss of Na(+)/Ca(2+)
      exchanger expression, as determined using immunocytochemistry and Western blots.
      Hypoxic Na(+)/Ca(2+) exchanger 1 inhibition occurs at the level of transcription,
      as mRNA for Na(+)/Ca(2+) exchanger 1 was significantly suppressed by hypoxia. Our
      results show hypoxia perturbs Ca homeostasis in astrocytes via the suppression of
      Na(+)/Ca(2+) exchanger 1 expression.

PMID- 16603929
TI  - ATP dependence of the non-specific ion channel in Torpedo synaptic vesicles.
AB  - Synaptic vesicles of Torpedo electromotor neurons contain a high amount of ATP.
      The concentration of total ATP is around 120 mM, whereas the free [ATP] is about
      5-6 mM. We examined the effect of intravesicular ATP on the non-specific ion
      channel in Torpedo-fused synaptic vesicles. It was found that this channel is
      closed when the ATP concentration is above 2 mM, but it is very frequently open
      at lower ATP concentrations. Unmasking this ion channel at a low ATP
      concentration may be significant for post-fusion control of transmitter release
      by the 'kiss and run' mechanism in normal conditions, while during metabolic
      stress it may underlie dissipation of important gradients across the vesicle
      membrane.

PMID- 16603930
TI  - Brain amyloid accumulates in aged rats with kaolin-induced hydrocephalus.
AB  - Amyloid beta-peptide (Abeta) accumulation in aged Sprague-Dawley rats (12 months)
      with kaolin-induced hydrocephalus was investigated by Abeta(1-40) and Abeta(1-42)
      immunohistochemistry at 2, 6 and 10 weeks after induction. The low-density
      lipoprotein receptor-related protein-1 transporting Abeta across the blood-brain
      barrier was assayed. Age-matched controls showed some positive Abeta staining,
      mainly in the choroid plexus. At 2 weeks after induction, Abeta staining of the
      arachnoid and subependymal layer was observed. At 6 weeks, larger Abeta
      accumulations were prominent at the endothelial and perivascular sites.
      Intraparenchymal Abeta positively stained accumulations occurred at 10 weeks.
      Microvessel lipoprotein receptor-related protein-1 staining was progressively
      reduced from 2 to 10 weeks. The pattern of Abeta deposition and lipoprotein
      receptor-related protein-1 loss suggests reduced Abeta clearance in chronic
      hydrocephalus.

PMID- 16603931
TI  - Nitric oxide/cyclic guanosine monophosphate-mediated growth cone collapse of
      dentate granule cells.
AB  - Controlling axon and dendrite elongation is critical in developing precise neural
      circuits. Using isolated cultures of dentate granule neurons, we established an
      experimental system that can simultaneously monitor the behaviors of axonal and
      dendritic outgrowth. Our previous study shows that axons and dendrites respond
      differentially to manipulated cyclic adenosine monophosphate signaling, but we
      report here that cyclic guanosine monophosphate exerts similar effects on axons
      and dendrites; that is, both axonal and dendritic growth cones collapsed after
      activation of cyclic guanosine monophosphate signaling. In addition, nitric oxide
      donor-induced growth-cone collapse was prevented by the inhibition of cyclic
      guanosine monophosphate signaling, and this effect again did not differ between
      axons and dendrites. Thus, unlike cyclic adenosine monophosphate, cyclic
      guanosine monophosphate modulates extending axons and dendrites in a similar
      manner.

PMID- 16603932
TI  - Aggregate distribution in frontal and motor cortex in Huntington's disease brain.
AB  - Insoluble protein aggregates have been considered a pathological hallmark of
      Huntington's disease and other polyglutamine disorders. In this study the number
      of aggregates was assessed in the superior frontal gyrus and motor cortex of
      seven Huntington's disease patients and was compared with the symptoms
      (motor/mood) these patients displayed during the course of the disease.
      Regardless of the pattern of symptoms present in the patients, there was a
      consistently higher number of nuclear and non-nuclear aggregates in the superior
      frontal gyrus than in the motor cortex. This suggests that there is a consistent
      regional difference in the density of aggregates and that this consistency is not
      reflected in the variable symptomatology between cases.

PMID- 16603933
TI  - Contralateral and ipsilateral motor effects after transcranial direct current
      stimulation.
AB  - Transcranial direct current stimulation over the left motor area influenced both
      contralateral and ipsilateral finger sequence movements in seven healthy adults.
      Effects for the two hands were reversed: anodal stimulation improved right-hand
      performance significantly more than cathodal stimulation, whereas cathodal
      stimulation improved left-hand performance significantly more than anodal
      stimulation. The results show that stimulating a motor region directly, or
      indirectly by modulating activity in the homologous region on the opposite
      hemisphere, can affect motor skill acquisition, presumably by facilitating
      effective synaptic connectivity. This outcome provides evidence for the role of
      interhemispheric inhibition in corticomotor functioning, and also has
      implications for treatment methods aimed at facilitating motor recovery after
      stroke.

PMID- 16603934
TI  - Prosodic processing at the sentence level in infants.
AB  - We investigate whether 8-month-old infants can detect prosodic cues relevant in
      sentence structuring. We recorded event-related potentials to examine online
      responses to the processing of prosodic boundaries. Prior studies in adults have
      validated the closure positive shift as reflecting prosodic boundary perception
      during speech processing. The current study shows that in the event-related
      potentials of 8-month-olds, a closure positive shift is elicited in relation to
      the prosodic boundaries in speech, suggesting that these infants are able to
      structure speech input into prosodic units on a neurophysiological basis similar
      to that seen in adults. A delay in latency of the infant closure positive shift,
      however, suggests that children's exploitation of prosodic boundaries for the
      segmentation of the speech stream is still developing.

PMID- 16603935
TI  - Brain mechanism of cognitive conflict in a guessing Chinese logogriph task.
AB  - To investigate the neural substrates of cognitive conflict in high-level thought
      processing, we recorded event-related potentials while participants thought about
      the logogriph answers. We identified three states after the answers were
      provided: (1) the answer given was just what the participants initially guessed
      (No-aha answer). (2) Participants could understand the answer given correctly
      although they had not got the answer themselves (Aha answer). (3) Participants
      could not understand the correct answer offered (Uncomprehended answer). Results
      showed that, relative to the No-aha answer, the Aha and Uncomprehended answers
      elicited more negative event-related potential deflections between 250 and 400
      ms. The dipole analysis localized the generator of the difference waves (Aha
      minus No-aha answer) to the anterior cingulate cortex. Thus, it might reflect the
      cognitive conflict center between familiar and new ways of processing the
      logogriphs.

PMID- 16603936
TI  - Effect of protein kinase Cbeta inhibitor on Ca2+ homeostasis in diabetic sensory
      neurons.
AB  - To elucidate the direct effect of selective protein kinase Cbeta inhibitor
      LY333531 on diabetic sensory neurons, we examined intracellular Ca(2+)
      concentration in isolated rat dorsal root ganglion neurons using the fluorescent
      Ca(2+) indicator fura-2. The duration of calcium transients induced by high (50
      mM) extracellular K in small diabetic dorsal root ganglion neurons was
      significantly prolonged compared with that in control neurons. This prolonged
      intracellular Ca concentration elevation in diabetic neurons was normalized
      rapidly and reversibly by LY333531 in a dose-dependent manner, and the effect of
      LY333531 was completely abolished by pretreating the neurons with mitochondrial
      calcium uniporter inhibitor, Ruthenium 360. These results suggest that LY333531
      has an ameliorating effect on calcium homeostasis of diabetic sensory neurons via
      mitochondrial calcium buffering.

PMID- 16603937
TI  - Still waiting for ratio legislation.

PMID- 16603938
TI  - HAIs: more education needed.

PMID- 16603939
TI  - Positive outcomes? Good isn't good enough.

PMID- 16603941
TI  - Take the fear out of the figures.

PMID- 16603942
TI  - Taming burnout's flame.

PMID- 16603943
TI  - The performance improvement decision.

PMID- 16603944
TI  - Policy spotlight: staffing plans and ratios.

PMID- 16603945
TI  - No brawn needed.

PMID- 16603946
TI  - Save our skin: initiative cuts pressure ulcer incidence in half.

PMID- 16603947
TI  - Infection control: start with skin.

PMID- 16603948
TI  - After hours OR team?

PMID- 16603949
TI  - Guarding against vascular site infection.

PMID- 16603951
TI  - The Magnetic pull.

PMID- 16603952
TI  - Do needleless connectors increase bloodstream infection risk?

PMID- 16603953
TI  - Can we thrive, despite the faculty shortage?

PMID- 16603954
TI  - Challenge: public reporting.

PMID- 16603955
TI  - Intravitreal bevacizumab treatment of choroidal neovascularization secondary to
      age-related macular degeneration.
AB  - PURPOSE: To describe the short-term anatomical and visual acuity responses after
      intravitreal injection of bevacizumab (Avastin, Genentech) in patients with
      choroidal neovascularization (CNV) secondary to age-related macular degeneration
      (AMD). METHODS: We conducted a retrospective study of patients with CNV secondary
      to AMD who were treated with intravitreal injection of bevacizumab (1.25 mg)
      during a 3-month period. Patients underwent best-corrected Snellen visual acuity
      testing, optical coherence tomography, and ophthalmoscopic examination at
      baseline and follow-up visits. RESULTS: There were 266 consecutive eyes of 266
      patients who received injections, and follow-up information was available for 251
      (94.4%). The mean age of the patients was 80.3 years, the mean baseline visual
      acuity was 20/184, and 175 (69.7%) had inadequate response to alternate methods
      of treatment. At the 1-month follow-up (data available for 244 patients), the
      mean visual acuity was 20/137 (P < 0.001 as compared with baseline), and 74
      (30.3%) of patients had improvement in visual acuity as defined by a halving of
      the visual angle. At the 2-month follow-up (data available for 222 patients), the
      mean visual acuity was 20/122 (P < 0.001), and 78 (31.1%) of patients had visual
      improvement. At the 3-month follow-up (data available for 141 patients), the mean
      visual acuity was 20/109 (P < 0.001), and 54 (38.3%) of patients had visual
      acuity improvement. The mean central macular thickness at baseline was 340 mum
      and decreased to a mean of 247 microm at month 1 (P < 0.001) and 213 microm at
      month 3 (P < 0.001). At 1 month, two patients had mild vitritis, as did one
      patient at 2 months, who had a history of recurrent uveitis. No endophthalmitis,
      increased intraocular pressure, retinal tear, or retinal detachment occurred. The
      risk for thromboembolic disorders did not seem to be different than reported
      previously in studies concerning macular degeneration. CONCLUSION: There were no
      apparent short-term safety concerns for intravitreal bevacizumab injection for
      CNV. Treated eyes had a significant decrease in macular thickness and improvement
      in visual acuity. The follow-up was too short to make any specific treatment
      recommendations, but the favorable short-term results suggest further study is
      needed.

PMID- 16603956
TI  - Subthreshold transpupillary thermotherapy for early resolution of foveal
      subretinal fluid in choroidal metastasis.
AB  - PURPOSE: To report the effectiveness of subthreshold transpupillary thermotherapy
      (TTT) in the early resolution of subretinal fluid at the fovea in solitary
      choroidal metastasis. METHODS: : Three consecutive patients who had
      adenocarcinoma of the lung with choroidal metastasis and macular subretinal fluid
      were treated by subthreshold TTT. Tumor response and fluorescein angiographic and
      visual results were recorded. RESULTS: Fluorescein angiography revealed solitary
      choroidal metastasis at the posterior pole with subretinal fluid in all patients.
      Initial best-corrected visual acuity in Patient 1, a 57-year-old man, was 40/200.
      Instead of usual high laser intensity, three applications of TTT, 400-mW power, 3
      mm size, and 1-minute duration, were performed over the tumor mass. Repeated
      treatment with the same regimen was performed after 1 week. Visual acuity
      improved to 20/25 2 months after treatment. Best-corrected visual acuity in
      Patient 2, a 68-year-old woman, was 10/200 in the right eye before treatment.
      Visual acuity improved to 80/200 after treatment and remained stable for 14
      months. Visual acuity improved from 20/100 to 20/60 in a third patient 2 months
      after treatment. The disappearance of subretinal fluid over the fovea was noted
      by fluorescein angiography 2 months after laser treatment and remained stable
      until the end of follow-up. CONCLUSION: Improvement of visual acuity and
      cessation of fluorescein leakage in the tumor showed that subthreshold (i.e.,
      biomicroscopically invisible laser effect) TTT served as an effective treatment
      modality in the early resolution of macular subretinal fluid in choroidal
      metastasis. Multiple sessions of subthreshold TTT are safe to apply very close to
      the macula.

PMID- 16603957
TI  - Verteporfin photodynamic therapy for choroidal neovascularization associated with
      toxoplasmic retinochoroiditis.
AB  - PURPOSE: To evaluate the efficacy and safety of verteporfin photodynamic therapy
      (V-PDT) for young adults and children with subfoveal choroidal neovascularization
      (CNV) associated with toxoplasmic retinochoroiditis. METHODS: Patients with
      subfoveal CNV associated with toxoplasmic retinochoroiditis were treated with V
      PDT and prospectively followed up. Before V-PDT and during follow-up, patients
      underwent visual acuity testing, complete ophthalmic examination including color
      photography, angiography with fluorescein and/or indocyanine green, and optical
      coherence tomography. The decision to retreat CNV was based on the criteria used
      in the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy
      investigation. RESULTS: Eight patients (5 males and 3 females) were treated at a
      mean age of 15.3 years (range, 5-31 years). CNV was 100% classic or predominantly
      classic in all study patients. Mean visual acuity increased from 20/225 (range,
      20/400 to 20/50) to 20/123 (range, 20/200 to 20/25) during a mean follow-up
      period of 25 months (range, 5-49 months). Persistent closure of CNV was achieved
      in all eight patients (mean number of treatments, 1.75). Vascular anastomosis
      developed in the treated area in two patients, but there was no additional visual
      loss. No significant adverse effects of V-PDT were observed. CONCLUSION: V-PDT
      for subfoveal CNV associated with toxoplasmic retinochoroiditis appears to be
      effective and safe even in young adults and children. However, a longer follow-up
      is recommended to confirm our observations.

PMID- 16603958
TI  - Photodynamic therapy for vasoproliferative retinal tumors.
AB  - PURPOSE: To report our experience with photodynamic therapy (PDT) with
      verteporfin for patients with vasoproliferative retinal tumors (VPRTs). METHODS:
      Three patients with VPRTs who presented with macular exudative changes were
      treated with one session of PDT with 6 mg/m body surface area of verteporfin and
      a light dose of 100 J/cm at 689 nm delivered in 166 seconds. Biomicroscopy,
      fluorescein angiography, indocyanine green angiography, optical coherence
      tomography, and ultrasonography were performed before treatment and 1 month, 3
      months, 6 months, and 1 year after treatment; visual acuity was measured using
      Early Treatment Diabetic Retinopathy Study criteria. RESULTS: At the 1-year
      follow-up, all tumors responded with a reduction in size (mean height:
      pretreatment, 2.96 mm; posttreatment, 1.32 mm), and optical coherence tomography
      showed complete resolution of macular exudates. For all patients, fluorescein
      angiography evidenced reduction of leakage from the lesion, and indocyanine green
      angiography verified nonperfusion of the vascular channels. An improvement in
      visual acuity (average, 4.7 Early Treatment Diabetic Retinopathy Study letters)
      was observed. No retreatment was needed. CONCLUSION: PDT may represent an
      effective and safe modality of treatment for VPRTs because of its selectivity.
      Our study supports the application of a light dose of 100 J/cm, although further
      studies with larger numbers of cases and longer follow-ups are required.

PMID- 16603959
TI  - Pediatric rhegmatogenous retinal detachment in taiwan.
AB  - PURPOSE: To describe the clinical features and surgical outcomes in a series of
      pediatric patients with rhegmatogenous retinal detachments in Taiwan. METHODS:
      Retrospective study of pediatric patients (age 1 to 15 years) with rhegmatogenous
      retinal detachment dated between January 1995 and December 2004. Patients with
      perforating ocular trauma were excluded. Patients were divided into four groups
      according to the predisposing factors: Group 1, those with congenital or
      developmental anomalies; Group 2, those with trauma history; Group 3, those with
      myopia greater than -3 D but excluding patients in Groups 1 and 2; and Group 4,
      the others with miscellaneous etiologies. Patients' age, sex, medical history,
      ocular history, type of detachment, macular status, refractive status, previous
      visual acuity, number and type of surgeries performed, postoperative retinal
      status, and current visual acuity were recorded. RESULTS: Thirty-five eyes of 32
      patients were included in this study. The median age was 13 years, and 75% of
      patients were boys. There were 17 eyes (49%) in Group 1, 8 in Group 2 (23%), 8 in
      Group 3 (23%), and 2 in Group 4 (6%). Bilateral retinal detachment was present in
      7 patients (22%). In Group 1, familial exudative vitreoretinopathy was present in
      7 eyes; retinopathy of prematurity was noted in 5 eyes; Marfan's syndrome was
      present in 3 eyes; mental and growth retardation was present in 2 eyes. Macula
      sparing retinal detachment was found in 3 eyes. Retinal attachment was achieved
      in 28/35 eyes. Visual recovery was modest. CONCLUSION: Congenital or
      developmental anomalies, myopia, and trauma were the most common risk factors for
      pediatric rhegmatogenous retinal detachment in Taiwan. Regular follow-up for
      children at risk of developing rhegmatogenous retinal detachment is necessary for
      early detection.

PMID- 16603960
TI  - Prospective evaluation of fundus changes in patients with orbital mass lesions.
AB  - PURPOSE: To study fundus changes associated with orbital mass lesions. METHODS:
      In a prospective, interventional case series, 28 patients undergoing surgery for
      discrete orbital masses had detailed fundus examination under dilation using
      direct and indirect ophthalmoscopy. Preoperative visual acuity and the amount and
      duration of proptosis were noted. Fundus photographs were taken, and
      postoperative changes were documented. The main outcome measures were the
      frequency of various fundus changes and their correlation with other clinical
      features. RESULTS: Nineteen (68%) of 28 patients had fundus changes; the
      commonest change was optic disk edema, seen in 14 patients (50%). The mean amount
      of proptosis +/- SD was 7.7 +/- 7.1 mm for patients with fundus changes and 4.22
      +/- 2.1 mm for patients with normal fundus. Of 19 patients with fundus changes,
      12 (63%) had an intraconal mass, and 11 (58%) had globe indentation. Twenty
      patients (71%) had diminished visual acuity preoperatively; of these patients, 8
      (40%) had improvement in vision after surgery, 10 (50%) did not have any change
      in vision, and 2 (10%) had a postoperative decrease in visual acuity. Five (62%)
      of 8 patients with postoperative improvement in visual acuity had proptosis for <
      2 years before surgery was undertaken, while only 1 (10%) of 10 patients
      retaining their preoperative vision had a duration of proptosis of < 2 years.
      CONCLUSION: Fundus changes are frequently seen with orbital masses. An increased
      amount of proptosis, intraconal location, and globe indentation are associated
      with fundus changes. Postoperative improvement in visual acuity is less likely in
      patients with a longer duration of symptoms.

PMID- 16603961
TI  - Coats disease: a lifetime disease.
AB  - PURPOSE: To document the recurrent nature of Coats Disease. METHODS: This study
      is a retrospective chart review approved by our Institutional Review Board.
      Thirteen patients (13 eyes) were diagnosed with Coats Disease starting in 1966.
      Age, visual acuity, time of onset, method of treatment, and the number and
      intervals of recurrences were documented. Recurrences were recorded once initial
      treatment proved successful and most exudates had absorbed. The length of follow
      up for each patient and the most recent visual acuity was recorded. RESULTS: The
      average follow-up period for the 13 patients was 12.4 years with a range from 4.0
      to 37.5 years. Eleven patients (85%) were male, two (15%) were female and all had
      unilateral involvement. The average age at diagnosis was 7.0 years with a range
      from 9 months to 27 years. Four out of the twelve treated patients (33%) had
      recurrences, and three of the four had multiple recurrences. The average elapsed
      time from successful treatment to the first recurrence was 4.3 years with a range
      from 3.3 to 5.4 years. The average number of recurrences was 3.3. CONCLUSION:
      Coats Disease can recur so it is important that parents educate any affected
      children regarding the necessity of follow-up, including throughout their adult
      years.

PMID- 16603962
TI  - De novo intraocular retinoblastoma development after chemotherapy in patients
      with hereditary retinoblastoma.
AB  - OBJECTIVE: Identification of incidence and risk factors for recurrence of de novo
      retinoblastomas after chemotherapy treatment in patients with hereditary
      retinoblastoma. METHODS: A retrospective, case-control study of 32 patients (50
      eyes) with sporadic or familial bilateral retinoblastomas was conducted. Patients
      received a systemic chemotherapy regimen applying three courses of a combination
      of three drugs (including vincristine, etoposide, carboplatin, or
      cyclophosphamide) followed by additional local therapy. The primary outcome
      analyzed was the development of retinoblastomas, probably arising as the cause of
      a new mutational event (de novo) after completion of chemotherapy treatment.
      RESULTS: Patients were treated with an average of 5.8 +/- 1.8 chemotherapy
      courses (4.6 +/- 2.4-year follow-up time). Development of de novo tumors occurred
      in 48% of the treated eyes. These tumors occurred during chemotherapy treatment
      or within 7 months of chemotherapy completion. No de novo tumors developed in
      patients older than 3.2 years. Children who developed de novo tumors were
      significantly younger at the time of diagnosis (6.7 +/- 6.3 months vs 14.4 +/-
      11.4 months, P < 0.001), and had a significantly lower number of tumors per eye
      at treatment begin (2.6 +/- 2.3 tumors vs 4.3 +/- 6.4 tumors, P < 0.001). The
      difference of the total numbers of retinoblastomas that developed per eye between
      the patients that developed de novo retinoblastomas during or after chemotherapy
      and patients who did not was not statistically significant (4.9 +/- 2.7 and 4.3
      +/- 6.4, respectively, P = 0.8). No eye was lost because of de novo
      retinoblastoma development, and 92% of the eyes were preserved. CONCLUSIONS: De
      novo retinoblastomas developed both during and after completion of chemotherapy
      treatment. Younger children were at a significantly higher risk for developing de
      novo intraocular retinoblastomas. Good tumor control and eye preservation rates
      were achieved with regular and frequent control examinations in addition to the
      immediate treatment of de novo retinoblastomas.

PMID- 16603963
TI  - Glutamate levels in aqueous humor of patients with retinal artery occlusion.
AB  - PURPOSE: We analyzed the levels of glutamate and other amino acids in aqueous
      humor of patients with retinal artery occlusion (RAO) to determine whether
      glutamate is associated with retinal ischemia in RAO. METHODS: Aqueous humor
      samples were obtained from nine RAO patients by paracentesis performed as an
      emergent therapeutic intervention and from nine cataract patients without other
      ocular disease who served as controls. Aspartic acid, glutamate, taurine, and
      alanine concentrations were determined using high-performance liquid
      chromatography. RESULTS: The glutamate level in aqueous humor of patients with
      RAO (4.46 +/- 1.62 micromol/L) was significantly higher than that in controls
      (2.98 +/- 1.12 micromol/L) (P < 0.05). CONCLUSIONS: Elevated glutamate levels in
      aqueous humor may indicate diffusion of vitreous glutamate released from the
      damaged retina due to acute retinal ischemia in RAO. An increase in the
      extracellular glutamate level may play an important role in ischemic retinal
      damage in RAO.

PMID- 16603964
TI  - Effect of nos inhibition on retinal arterial and capillary circulation in early
      arterial hypertension.
AB  - BACKGROUND: Arterial hypertension is involved in the pathogenesis of end organ
      damage by influencing the ability of the vascular endothelium to produce nitric
      oxide (NO). This study analyzes changes of retinal and systemic NO-dependent
      circulation parameters by inhibiting nitric oxide synthase (NOS) in both
      hypertensive and normotensive individuals. METHODS: In a double-blind crossover
      trial, 19 hypertensive patients (H, age 28.2 +/- 0.9 years) and 19 normotensive
      controls (N, age 26.9 +/- 0.9 years) were randomized treated either with
      candesartan or placebo. Both retinal capillary flow (RCF) and mean blood flow
      velocity of the central retinal artery (VCRA) were registered before and after
      NOS inhibition with N-monomethyl-L-arginine (L-NMMA, 3 mg/kg). In a subpopulation
      mean arterial pressure (MAP), cardiac output (CO), and the total peripheral
      resistance (TPR) were determined simultaneously. RESULTS: Changes from baseline:
      In normotensive and hypertensive subjects infusion of L-NMMA led to an increase
      of MAP (N, +13.3 +/- 1.8%, P < 0.01; H, +14.3 +/- 2.4%, P < 0.01) and TPR (N,
      +36.9 +/- 3.8%, P < 0.01; H, +45.0 +/- 4.5%, P < 0.01), and to a decrease of CO
      (N, -21.1 +/- 1.5%, P < 0.01; H, -24.6 +/- 2.3%, P < 0.01). The L-NMMA effect on
      VCRA and RCF differed between controls and hypertensives. VCRA changed by + 17.3
      +/- 6.2% (P < 0.05) and RCF by -7.3 +/- 3.0% (P < 0.05) in controls. In
      hypertensive subjects corresponding results were + 9.5 +/- 5.2% (P = NS) and +
      2.7 +/- 3.8% (P = NS), respectively. The decrease of RCF due to L-NMMA was
      reduced in hypertension as compared to controls (P < 0.05). The calculated cross
      sectional area of CRA was reduced by -58.7% in controls and increased by + 31.1%
      in hypertensive subjects. There was no significant correlation between the flow
      in the systemic and retinal circulation. CONCLUSION: Only normotensives L-NMMA
      induces an acceleration of VCRA due to a probable vasoconstriction of the central
      retinal artery and despite of a reduced RCF. Already in early hypertension the
      NOS-dependent vascular tone in retinal arteries and capillaries is impaired. The
      regulation of the retinal capillary flow appeared to be independent from systemic
      circulation.

PMID- 16603965
TI  - Morphometric examination of human and monkey retinal ganglion cells within the
      papillomacular area.
AB  - PURPOSE: To examine the morphology of the retinal ganglion cells (RGCs) in the
      lesser characterized area lying between the optic disk and the macula that
      consists of the central papillomacular area (PMA) and the arcuate papillomacular
      bundle (PMB). METHODS: Nineteen human and 10 monkey (Macaca fascicularis) retinas
      obtained after death were used in the study. Perikaryal, axonal, and dendritic
      silhouettes were examined by postvital application of the fluorescent dye DiI,
      which specifically labeled RGCs when placed onto the optic fiber layer. The
      retinas were freed from surrounding tissue, prepared as flat mounts on a
      nitrocellulose filter, and fixed overnight in 4% paraformaldehyde. DiI diffuses
      along the membranes of ganglion cell axons, thereby completely labeling them,
      their cell bodies, and dendrites, which enables the RGCs to be examined with
      fluorescence microscopy. RESULTS: In both species, midget cells represented most
      of the RGCs within the PMA (96.15%) and possessed small, umbrella-like dendrites
      oriented toward the deeper retinal layers. Parasol cells were less abundant in
      both species and had small, typical symmetric dendrites. Also along the PMB,
      midget cells represented most cells (91.52%), whereas only 8.47% could be
      categorized as parasol cells. In both species, parasol cells of the PMB extended
      dendrites, which were oriented perpendicular to the axons. CONCLUSIONS: The data
      show that the PMA and PMB mainly contain small midget cells of typical morphology
      and size but with atypically oriented dendrites, which are only characteristic
      for this retinal area.

PMID- 16603966
TI  - MMP-2 and MMP-9 secretion by rpe is stimulated by angiogenic molecules found in
      choroidal neovascular membranes.
AB  - PURPOSE: Matrix metalloproteinases (MMP)-2 and -9 play an important role in the
      pathogenesis of choroidal neovascularization (CNV). Retinal pigment epithelial
      cells (RPE) are an important source of MMPs in the outer retinal environment,
      however little is known about the local factors that modulate MMP secretion in
      these cells. The purpose of this study was to determine the effects of CNV
      involved growth factors and the extracellular matrix molecule fibronectin on MMP
      2 and -9 secretion by cultured human RPE. METHODS: MMP-2 and -9 secretion was
      studied using gelatin zymography, Western blot, and ELISA assay of RPE culture
      supernatants. The effects of stimulating the cells for 36 hours with vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bGFG), tumor
      necrosis factor-alpha (TNF-alpha), or fibronectin (FN), all angiogenic factors
      found in CNV membranes, was determined. RESULTS: Resting RPE cells secreted MMP-2
      but not MMP-9. Stimulation with TNF-alpha induced secretion of MMP-9 and
      increased the secretion of MMP-2. MMP-2 secretion was also increased by
      stimulation with FN and VEGF, but not bFGF. CONCLUSION: The results indicated
      that the angiogenic molecules VEGF, FN, and TNF-alpha stimulate MMP-2 and -9
      secretion from RPE and thus further promote CNV.

PMID- 16603967
TI  - Diagnostic and therapeutic challenges.

PMID- 16603968
TI  - Macular star associated with Behcet disease.

PMID- 16603969
TI  - Indocyanine green angiographic findings in congenital grouped albinotic spots.

PMID- 16603970
TI  - Group B streptococcal endogenous endophthalmitis in a neonate.

PMID- 16603971
TI  - The question of macular hole: avulsed epiretinal membrane shadowing artifact in
      optical coherence tomography testing.

PMID- 16603972
TI  - Vasoproliferative tumor of the retina after spontaneous reattachment of
      rhegmatogenous retinal detachment.

PMID- 16603973
TI  - Photodynamic therapy for extrafoveal choroidal neovascularization associated with
      choroidal nevus.

PMID- 16603974
TI  - Autofluorescence imaging of acute posterior multifocal placoid pigment
      epitheliopathy.

PMID- 16603975
TI  - Optical coherence tomography findings in multiple evanescent white dot syndrome.

PMID- 16603977
TI  - Surgical removal of the internal limiting membrane in diabetic cystoid macular
      edema.

PMID- 16603978
TI  - Macroaneurysm on the optic disk associated with congenital retinal arterial
      malformation.

PMID- 16603980
TI  - iPods are the new Walkmans, only more so.

PMID- 16603981
TI  - Improving patient safety in the NHS.

PMID- 16603982
TI  - Correct use and deliberate misuse of manual lifting devices provided by the
      nursing home.

PMID- 16603983
TI  - Constipation in older patients: effects on quality of life.
AB  - Constipation, often related to diet, physical immobility, concurrent illness or
      multiple medication use, is common in older people. Despite potential for serious
      complications, constipation may often be overlooked. Management of constipation
      is a critical part of the care of older patients with chronic conditions. Risk
      assessment and appropriate nursing interventions and/or medication should mean
      that constipation can be minimized, preventing additional medication burden and
      reducing the risk of non-adherence. The relationship between quality of life and
      constipation has been assessed in numerous studies, showing that patients with
      constipation generally have an impaired quality of life compared with the general
      population, although studies in older patients are limited. In long-term
      survivors of colorectal or anal carcinoma, constipation is one of the factors
      that has the most negative impact on quality of life. Strategies for prevention
      and minimization of constipation have the potential to substantially improve
      quality of life for older people.

PMID- 16603984
TI  - Constipation services for children: the role of health visitor teams.
AB  - Constipation among children is a prevalent condition, yet poorly understood.
      There is little empirical evidence for 'best possible' configurations of
      services. This article presents a survey of Walsall health visitor team members
      (HVTMs) which aimed to identify the types of advice and care provided to young
      children with constipation, pathways to care and ideas for service improvement.
      Most HVTM consultations were parent-initiated. Few GPs referred children to
      HVTMs. HVTMs most commonly provided advice about fluids and diet -- only one
      prescribed medication. HVTMs identified the need for early intervention,
      consistent information for parents and a clear pathway for all health
      professionals to follow. Currently, a team from the local primary and hospital
      NHS trusts is developing an integrated care pathway for paediatric constipation.
      Success of such pathways depends on their adoption by GPs and hospital-based
      health professionals, and on evidence of efficacy arising from their evaluation.

PMID- 16603985
TI  - Role of the continence nurse in health promotion.
AB  - Incontinence is a distressing and unpleasant symptom, which impacts on a person's
      physical, social and psychological well-being. Nurses, like other healthcare
      professionals, have a role in health promotion. Continence nurses can identify
      causes, create treatment plans and empower patients with incontinence to be
      involved in all aspects of their care. The five approaches to health promotion:
      medical, behavioural, educational, public policy and empowerment, are a useful
      framework to discuss the role of the nurse in the promotion of continence.

PMID- 16603986
TI  - Breast-feeding initiation among post-Caesarean women of the Negev, Israel.
AB  - The objectives of the study were to increase post-Caesarean breastfeeding rates
      and decrease timing of post-Caesarean breastfeeding initiation in multicultural
      populations following a post-Caesarean breastfeeding intervention. The study was
      a prospective population-based evaluation of a breastfeeding intervention for
      post-Caesarean women of different cultures at a southern Israeli hospital. The
      study population consisted of 570 Jewish and Muslim post-Caesarean women who had
      delivered healthy, term infants. The control group (n=264) received standard
      hospital care and the intervention group (n=306) received early, culturally
      sensitive, post-Caesarean breast-feeding guidance and education by trained
      professionals. Timing of post-Caesarean maternal-infant contact and breastfeeding
      initiation outcomes for the Jewish and Muslim women significantly improved
      following the intervention.

PMID- 16603987
TI  - Legal aspects of continence.
AB  - This article considers the law which applies to the supply of incontinence
      equipment. It considers the liability of the employee and the primary care trust
      and possible defences to an action for negligence and the right to acquire
      records relating to an incident which has arisen. It also looks at the health and
      safety laws which apply to the provision of safe equipment, and considers the
      patient's right to access health services and the issues which arise when
      resources are limited.

PMID- 16603988
TI  - The management and nursing care of cirrhotic ascites.
AB  - Over 3000 deaths from cirrhosis/chronic liver disease are reported in England and
      Wales each year. However, these figures may underestimate the true extent of
      liver-related mortality by between 30-60%. As more patients with advanced
      cirrhosis are being nursed outside of specialist centres, it is essential that
      health professionals are aware of the management of cirrhotic-related
      complications. Defined as fluid within the peritoneal cavity, ascites is one of
      the most frequent complications of cirrhosis, and is considered as the marker of
      the transition from compensated to decompensated liver disease. The development
      of ascites is associated with a poor quality of life, increased risk of
      infections, renal failure and poor long-term outcomes. In recent years, however,
      there have been several advances in the management of ascites. This article will
      discuss both the pathophysiology, and the current medical, surgical and nursing
      management of this condition.

PMID- 16603990
TI  - Developing a complementary therapy policy.
AB  - Increasingly, healthcare professionals from a variety of settings are looking to
      integrate complementary therapies into mainstream healthcare. Robust policy
      development is a prerequisite for effective integration and the building of
      sustainable services. Unfortunately many of those wanting to drive forward the
      complementary therapy agenda have little knowledge of policy development. For
      those individuals planning to integrate complementary therapies into care, this
      article will address some of the issues around developing a complementary therapy
      policy: the need for a robust policy, how to begin developing a policy and
      suggested inclusions for such a policy.

PMID- 16603989
TI  - The provision of nursing care for gay men with GI issues.
AB  - The holistic nursing care of the individual is a hallmark of high-quality care;
      this holistic approach means that the nurse will also have to take the sexuality
      of the person being cared for into account. This article promotes the notion of
      holism and, in particular, the care of one group of patients -- homosexual men.
      In this article the needs of the gay patient who has undergone GI surgery are
      discussed in respect to their sexuality. Key terms and concepts are considered. A
      therapeutic nurse-patient relationship can only be achieved if the needs of the
      patient are taken into account; the term that the patient chooses to use when
      identifying his individual sexuality must be respected. Stigma, discrimination
      and prejudice are unwanted results of a failure to respect an individual and
      should be avoided. There are several instances where stereotyping and myth may
      occur concerning the gay patient who has undergone GI surgery, and erroneous
      assumptions made about the patient can thwart the unique nurse-patient bond.

PMID- 16603991
TI  - Does the NHS need more physician's assistants?

PMID- 16603992
TI  - Nurse prescribing reaches new horizons.

PMID- 16603993
TI  - Introduction of a pain scale for palliative care patients with cognitive
      impairment.
AB  - AIM: To describe the development and introduction of a pain scale for patients
      with cognitive impairment who are admitted to homes for older people and nursing
      homes in the region of northwest Flanders in Belgium. DESIGN: A questionnaire
      comparing the Abbey and Pain Assessment in Advanced Dementia (PAINAD) scales was
      distributed in 17 homes; 185 care providers participated, evaluating 157
      patients. FINDINGS: Approximately half of the care providers evaluated both
      scales as being good measures of pain and easy to use. Of the different items
      scored in both scales, care providers agreed upon three indicators as being most
      valuable to use for measuring pain: facial expression; vocalization; and body
      language. CONCLUSION: The findings were not conclusive for the introduction of
      either Abbey or PAINAD. Based on the results, a simplified pain observation scale
      consisting of three items was developed. It has been introduced in the homes of
      the region and is being tested currently.

PMID- 16603994
TI  - Developing guidelines for syringe driver management.
AB  - The aim of this project was to develop clinical practice guidelines for the use
      and administration of pharmacological agents for symptom control via syringe
      drivers within Australia. By developing evidence-based clinical practice
      guidelines for the use of this common device, this project aimed to improve
      patient outcomes, reduce practice variation, minimize errors and encourage more
      efficient use of resources. A literature review identified current literature
      regarding syringe driver management and an expert panel was assembled to assist
      in the development of the guidelines. The development of these practice
      guidelines provides an example of how palliative care practitioners can use a
      framework of contemporary evidence to enhance clinical practice.

PMID- 16603995
TI  - Exploring cancer genetics and care of the family: an evolving challenge for
      palliative care.
AB  - There is a growing scientific understanding and increasing public awareness of
      the influence of genetics on the development of cancer. This article, which is
      based on a review of the literature, focuses on how the awareness of genetic
      predisposition to cancer is affecting patients and their families. It highlights
      the way that risk assessment for predisposition to cancer can conflict with
      traditional models of informed consent and can cause concern for families. It
      suggests that there is need for informed discussion within palliative care about
      how best to support families with concerns about a family history of cancer.

PMID- 16603997
TI  - Keeping up the pressure: pushing palliative and hospice care higher up the
      political agenda.

PMID- 16603996
TI  - Out-of-hours medical cover in community hospitals: implications for palliative
      care.
AB  - BACKGROUND: The new General Medical Services contract in England means many GPs
      have transferred out-of hours work to their primary care organization, with
      implications for continuity of palliative care in community hospitals. AIM: To
      examine existing arrangements for out-of-hours medical cover in community
      hospitals, focusing on palliative care. METHODS: Telephone survey of community
      hospital managers/senior nurses across England and Wales. RESULTS: Interviews (n
      = 62) revealed nursing staff were satisfied with existing out-of-hours care.
      Concern was expressed about the future of out-of-hours medical care from GPs as
      new services will cover larger areas, meaning unknown doctors may attend, taking
      longer to arrive. CONCLUSION: Arrangements for out-of-hours medical cover in
      community hospitals are in transition, threatening the continuity of care for
      dying patients.

PMID- 16603998
TI  - Implementation of an adaptation programme for Filipino nurses in a UK adult
      cancer hospice.
AB  - The UK has a history of recruiting international nurses successfully. This
      recruitment places a responsibility on healthcare providers to offer a suitable
      adaptation programme in order to prepare the internationally recruited nurses for
      registration with the regulatory body. This article outlines the organization and
      implementation of such an adaptation programme as a joint venture between a
      higher education provider and a local hospice which was designed specifically to
      meet the needs of palliative care patients.

PMID- 16603999
TI  - [The pneumologist regarding smoking cessation].

PMID- 16604000
TI  - [Unknown effects of tobacco smoke exposure].

PMID- 16604001
TI  - [Evaluation tools: what should be used?].

PMID- 16604002
TI  - [Must we evaluate everything?].

PMID- 16604003
TI  - [Update on pharmacologic therapies and future perspectives].

PMID- 16604004
TI  - [Risk reduction strategy in patients with COPD].

PMID- 16604005
TI  - [How to motivate the hesitating patient?].

PMID- 16604006
TI  - [The consultation on lung and tobacco in 30 minutes].

PMID- 16604007
TI  - [How to prevent recurrence in smoking?].

PMID- 16604008
TI  - [Advantages of multidisciplinary management of smokers].

PMID- 16604009
TI  - [Are substitutes really part of therapy?].

PMID- 16604010
TI  - [Indications and practical issues concerning oxygen therapy].
AB  - INTRODUCTION: The initiation of oxygen therapy for acute or chronic respiratory
      failure is a common medical intervention, both for hospital in-patients and in
      out-of-hospital emergency settings. Oxygen therapy is also frequently initiated
      by paramedics or nurses, without any initial medical prescription, in acutely ill
      patients. STATE OF THE ART/PERSPECTIVES: It is important to remember that oxygen
      is a pharmaceutical drug, and its prescription should therefore be considered
      within treatment guidelines. Two main pathological situations may be encountered:
      tissue hypoxia and acute/chronic hypoxemia. CONCLUSION: Physicians should be
      aware of the clinical signs that may indicate the presence of hypoxia and the
      pathological situations that may lead to hypoxemia. They must also be aware of
      the potential complications, in particular CO(2) retention in patients with
      chronic type II respiratory failure as well as the overall indications, and
      practical issues concerning oxygen therapy.

PMID- 16604011
TI  - [The bronchial response to inhaled formaldehyde].
AB  - INTRODUCTION: Formaldehyde is an ubiquitous indoor chemical polutant.
      Occupational exposure to high concentrations has revealed its irritant and
      allergenic potential. Nevertheless, domestic exposure to low concentrations may
      also have an effect on respiratory health in a non-specific way, just as has been
      found for other pollutants. STATE OF KNOWLEDGE: Potentiation of the response to
      allergens has been observed in animals and children. This effect has also been
      found on respiratory symptoms, with a 39% increase in the risk of asthma for a
      domiciliary exposure of more than 60 microgrammes.m(-3). We have recently been
      able to show, in a study with asthmatics sensitised to house dust mite, that the
      response to allergen provocation was increased following a 30 minutes exposure to
      100 microgrammes.m(-3) formaldehyde. VIEWPOINT AND CONCLUSIONS: All the data show
      that mild exposure to formaldehyde in the home is sufficient to provoke
      sensitisation and also an aggrevation of symptoms in patients with allergic
      asthma. Taking into account the published evidence it is advisable that the
      concentrations of formaldehyde in domestic products should be made known in order
      to improve domiciliary air quality.

PMID- 16604012
TI  - [Treatment of epithelial thymic tumours: towards a multidisciplinary management].
AB  - INTRODUCTION: Thymic epithelial tumours (TET) are rare. Their optimal management
      is still not well defined on account of their rarity and the consequent
      difficulty of clinical research into the subject. This review presents the
      current clinical and therapeutic data, emphasising the need for a
      multidisciplinary management of advanced stage TET. CURRENT SITUATION: Three
      situations may be defined: localised tumours requiring radical surgery following
      a careful search for associated paraneoplastic syndromes; tumours with capsular
      invasion requiring surgery and adjuvent radiotherapy; advanced stage TET where
      only multimodal treatment is capable of improving the prognosis by increasing the
      percentage of complete resections while optimising local control with adjuvent
      radiotherapy. VIEWPOINT: An evaluation of the multimodal strategies for the
      treatment of advanced stage TET requires the establishment of multidisciplinary
      collaborative trials. The contribution of new therapies, somatostatin analogues
      and targeted therapies needs to be defined. CONCLUSIONS: The management of
      advanced stage TET should rest upon a multidisciplinary dialogue between a team
      of specialists, ideally in the framework of collaborative trials.

PMID- 16604013
TI  - [Smoking and smoking cessation programs: what's at stake for the respiratory
      physician?].

PMID- 16604014
TI  - [Tools for assessing healthcare delivery].
AB  - INTRODUCTION: Assessing the quality of care has become an essential part of the
      medical process. In France, the Professional Practice Evaluation requires a sound
      knowledge of these techniques. BACKGROUND: The different tools that can be used
      to carry out quality assessment are presented, with their specific applications.
      Two main categories can be used. The first are information synthesis techniques
      such as consensus conferences, practice guidelines, and panellist's
      appropriateness rating. The second category is based on comparison to a
      reference: clinical audit, targeted clinical audit, or appropriateness evaluation
      protocols. Other, less commonly employed approaches include a problem solving
      approach, which is often included in total quality management, clinical care
      pathway, risk management, mortality morbidity conference, adverse event
      monitoring, and statistical process control charts. VIEWPOINT: These tools will
      be widely used in the next few years, because the recent changes in French law
      could increase their use. CONCLUSION: A good knowledge of these techniques is
      needed in order to improve quality assessment.

PMID- 16604015
TI  - [Immune mediated intra-alveolar haemorrhage in the adult].
AB  - INTRODUCTION: The diagnosis of diffuse intra-alveolar haemorrhage (DAH) is
      suggested by the combination of haemoptysis, anaemia and pulmonary infiltrates.
      Broncho-alveolar lavage produces macroscopically haemorrhagic fluid and/or
      haemosiderin laden macrophages. The diagnostic approach should allow distinction
      between immune mediated and other causes on account of the therapeutic
      implications. BACKGROUND: The main immunological causes are small and medium
      vessel vasculitis (Wegener's granulomatosis, microscopic polyangeitis), lupus and
      Goodpasture's syndrome. Other immune disorders are only rarely involved. The
      association of DAH with an acute glomerulonephritis, indicating the pulmonary
      renal syndrome, extra-thoracic involvement and immunological abnormalities
      suggest an immune aetiology. Immunosuppressant treatment should be started as
      soon as possible with corticosteroids often combined with intravenous
      cyclophosphamide. Plasmapharesis is indicated for Goodpasture's syndrome and
      poorly responding lupus. Aggravating factors such as hypervolaemia and disorders
      of haemostasis should be searched for and treated. Hospital mortality is close to
      20%. VIEWPOINT AND CONCLUSION: Immune mediated DAH is a disorder whose rarity
      justifies the establishment of a national registry with the aim of developing
      standardised diagnostic and therapeutic strategies.

PMID- 16604016
TI  - [Cellular signalling pathways and pathophysiology of pulmonary arterial
      hypertension].
AB  - INTRODUCTION: Pulmonary arterial hypertension (PAH) is a disease of complex
      aetiology involving in varying degrees both genetic and environmental factors.
      BACKGROUND: Thanks to progress in biology over the past 15 years the
      physiological consequences of cellular and molecular abnormalities are much
      better understood. Recent work has allowed better understanding of the different
      cellular signalling pathways controlling pulmonary vascular tone and cell growth.
      It appears that these pathways form a dense and complex network involving several
      groups of molecules of which NO, cGMP, ET-1 and its receptors, are at the most
      important. VIEWPOINT: The pathophysiology of PAH may be regarded as a disorder of
      cellular signaling where molecular abnormalities disturb the balance between the
      different factors controlling vascular tone and cell proliferation. CONCLUSIONS:
      PAH may be viewed as a disease of cellular signalling where the molecular
      abnormalities not only affect a single signalling pathway but involve multiple
      cross-talks between groups of molecules controlling vascular smooth muscle tone
      and cell growth and differentiation.

PMID- 16604017
TI  - [Provision of smoking cessation therapy].
AB  - INTRODUCTION: Smoking cessation therapies help well motivated smokers give up and
      increase the chance of success. BACKGROUND: Medical, behavioural and cognitive
      cessation therapies are aimed at relieving the secondary effects of stopping
      smoking: withdrawal symptoms and the urgent need to smoke. A prolonged follow up
      helps to prevent relapse. VIEWPOINT: The education of doctors and the development
      of new drugs should increase the rate of successful withdrawal. CONCLUSION: All
      doctors, particularly respiratory physicians, should be involved in smoking
      cessation. The aim of this practical guide is to help them in everyday practice.

PMID- 16604018
TI  - [What is the impact of specialist guidelines outside their specialty?].

PMID- 16604019
TI  - [Mediastinal diagnosis, is there still a place for surgery?].

PMID- 16604020
TI  - [Preparing for the next influenza pandemic].

PMID- 16604021
TI  - [Asthma in Reunion. What lessons for France?].

PMID- 16604022
TI  - [Methacholine challenge testing in olympic athletes].

PMID- 16604023
TI  - [Asthma on the island of Reunion: an analysis of the severity and therapeutic
      management].
AB  - INTRODUCTION: Asthma is a common condition on the island of La Reunion but there
      are no epidemiological studies that analyse the prevalence, severity and
      management of the patients. METHODS: Two studies were undertaken: a CPAM (health
      insurance) study of 187 patients and an analysis of the data from 253 patients
      attending a specialist hospital clinic. RESULTS: In these two studies we found
      40% of patients were in GINA group 3 compared with 10% in metropolitan France.
      Recourse to the emergency department and admission to intensive care were common.
      There was under-evaluation by the treating physicians who did not classify
      patients correctly. This under-evaluation also occurred in prescribing with only
      1/3 of asthmatics in stages 2 and 3 receiving inhaled corticosteroids. Patient
      education was poor with 30% receiving a demonstration of inhaler technique and
      31% a functional evaluation. CONCLUSION: These studies show that the severity
      profile of asthma on La Reunion is comparable to that in other oceanic countries
      like Australia and New Zealand rather than metropolitan France. A population
      study is needed to assess the prevalence of asthma on the island of La Reunion.

PMID- 16604024
TI  - [Endobronchial ultrasound and PET positive mediastinal lymph nodes].
AB  - INTRODUCTION: In bronchial carcinoma when positron emission tomography with 18
      fluorodeoxyglucose (FDG-PET) shows increased emission in the mediastinal lymph
      nodes, confirmation by tissue biopsy is necessary. In this particular situation
      we have evaluated the use of real time lymph node aspiration under endobronchial
      ultrasound control. METHODS: Consecutive patients referred for staging and/or
      diagnosis of PET positive mediastinal nodes in the setting of suspected or
      confirmed bronchial carcinoma were included. The results of lymph node
      aspiration, performed under local anaesthesia in out-patients, were collected and
      if non-diagnostic surgical exploration was performed. RESULTS: 20 patients were
      studied between December 2004 and September 2005. The average number of
      ultrasound guided needle aspirations per patient was 4.8 +/- 1.2. Cytological or
      histological confirmation of malignancy was obtained by needle biopsy in 12
      patients. The 8 negative cases were confirmed by surgical biopsy. In this
      preliminary series the sensitivity, specificity and negative predictive value of
      ultrasound guided aspiration of PET positive nodes was 100%. CONCLUSION:
      Endobronchial ultrasound with needle aspiration should be considered a primary
      method of investigation of PET positive mediastinal lymph nodes.

PMID- 16604025
TI  - [Epidemiology and delays in the management of 355 patients with lung cancer].
AB  - BACKGROUND: The epidemiology of patients with lung cancer in a Seine-Saint-Denis
      hospital are reported, as well as causes of diagnostic and therapeutic delays in
      their management. MATERIAL AND METHODS: Retrospective analysis of cases diagnosed
      from January 1, 1997 to December 31, 2003. RESULTS: Of 355 cases, 15.8% were
      women; the average age was 62 +/- 11. Mean smoking history was 50 +/- 24 pack
      years. Women were more likely to be non-smokers than men (16% and 1%
      respectively, p < 0.01) and were more likely to present at a young age (under the
      age of 50: 26.8% and 13.7% respectively, p < 0.05). Among women, adenocarcinoma
      was more frequent (41% vs. 25%, p < 0.05), and often presented with stage IV
      disease (74%). Squamous cell carcinoma occurred more frequently with increasing
      age (18.7% vs. 32.2% before and after the age of 60, p < 0.01). The median pre
      hospital, diagnostic and treatment delays were respectively 30, 10 and 9 days,
      the global delay from first symptom to treatment was 62 days. Surgery increased
      therapeutic delay by 20 days. CONCLUSION: Our results are complementary to those
      found in KBP-2000-CPHG study. Young women are diagnosed at a late stage.
      Influence of delays on prognosis is not proved and require others studies.

PMID- 16604026
TI  - [Exacerbations of COPD: An audit of emergency department practice in France].
AB  - INTRODUCTION: Exacerbations of COPD are potentially serious events, the
      recognition and treatment of which appear to be poorly understood by both
      patients and doctors. The aim of this study is to describe, on the basis of two
      case histories, the management of exacerbations of COPD in emergency departments,
      to compare it with the current guidelines and to evaluate the extent of use of
      non-invasive ventilation in decompensated COPD. METHODS: The study took place
      between February and June 2004. Two case histories describing one moderate and
      one severe exacerbation with respiratory failure were written by the authors of
      the study and submitted to an emergency physician in a university hospital and a
      district hospital in each region. RESULTS: 110 questionnaires were returned from
      20 university hospitals and 25 district hospitals. Only 38% of the episodes were
      identified correctly. 20% of doctors did not regard dyspnoea as a clinical sign
      of an exacerbation. 22% of doctors never prescribed bronchodilators, even in
      severe cases. Finally, non-invasive ventilation (NIPV) was used for only 9% of
      the moderate and 56% of the severe exacerbations. DISCUSSION: This study,
      although limited by certain factors, illustrates a number of points in need of
      improvement in the recognition and treatment of exacerbations of COPD in
      emergency departments, the use of NIPV, and the collaboration between emergency
      physicians, intensivists and respiratory physicians.

PMID- 16604027
TI  - [Preliminary study of smoking in medical and paramedical staff at the Centre
      Hospitalier National de Fann Dakar].
AB  - BACKGROUND: Smoking represents a major threat to public health, being responsible
      for considerable morbidity and mortality. We undertook this study to establish
      the prevalence of smoking among personnel at the Centre Hospitalier National de
      Fann, their smoking habits and the attitude of staff to the problems caused by
      smoking as well as their understanding of their role in promoting smoking
      cessation. METHODS: A prospective study was undertaken between February and April
      2004 in which a standardised, anonymous, self-completion questionnaire in French
      was administered to 262 medical and paramedical staff at the CHN de Fann.
      RESULTS: The response rate was 95%. The biggest single group of respondents came
      from the infectious diseases service (24.5%). 63% of participants were
      paramedical and 54% of respondents were male. The mean age of respondents was
      39.2 for men and 35.9 for women. 11.6% were smokers and 13.3% were ex-smokers.
      The mean age of ex-smokers was 43.8 years with a male/female ration of 7.25 to 1.
      Among the ex-smokers 51.7% had stopped smoking within the last 10 years with
      health problems the most commonly cited reason for quitting (24.2%), followed by
      guilt (21.2%). Smokers had a mean age of 38.6 with a male to female ratio of 8.6
      to 1. Mean age at which they had started to smoke was 14.3 for women and 21 for
      men with a mean duration of smoking of 21 in women and 17 in men. 96.6% smoked
      cigarettes with 31% smoking > 20 cigarettes per day. 75.9% of our smokers had
      tried to quit at least three times. 86.2% wished to stop but only 48.3%
      considered getting medical and or psychological support to help them to quit. The
      Fagerstrom score showed a high level of dependency in 27.6% of smokers. More than
      half the total population studied (65.6%) thought that healthcare workers should
      help others to stop smoking and 75.5% thought that they had influence to do this.
      CONCLUSION: Healthcare workers in Senegal have an opportunity and a
      responsibility to promote smoking cessation. Legislative proposals and smoking
      cessation clinics should help to combat the tobacco epidemic.

PMID- 16604028
TI  - [Latent pneumocystis infection revealed after introduction of highly active
      antiretroviral therapy].
AB  - INTRODUCTION: Soon after the introduction of antiretroviral therapy for HIV
      infection, some patients may develop an inflammatory immune reconstitution
      syndrome, in the presence of clinically unsuspected infection. CASE REPORT: We
      describe a 31 year old patient, who presented with a lymphoid interstitial
      pneumonia associated with HIV infection. Unexpectedly, 15 days after the
      beginning of antiretroviral therapy, he developed a worsening of his respiratory
      function due to Pneumocystis infection. CONCLUSION: The appearance or aggravation
      of pulmonary symptoms, after highly active antiretroviral therapy has been
      initiated should lead to suspicion of an opportunist infection. Specific sampling
      must be considered.

PMID- 16604029
TI  - [Acute encephalopathy after infusion of paclitaxel].
AB  - INTRODUCTION: Paclitaxel is an anti-neoplastic agent commonly used in the
      treatment of primary bronchial carcinoma and tumours of the breast and ovary. Its
      toxicity, haematological and peripheral neuropathy, are well known. On the other
      hand central nervous system toxicity is rare. CASE REPORT: We report a case of
      acute encephalopathy, occurring eight hours after infusion of Paclitaxel, in a
      patient treated for adenocarcinoma of the lung. It included drowsiness, confusion
      and hallucinations, and resolved completely after ten days. The diagnosis of
      encephalopathy secondary to Paclitaxel injection was reached after exclusion of
      other possible aetiologies. CONCLUSIONS: Acute encephalopathy is a rare
      complication of intravenous Paclitaxel treatment. The pathophysiology of this
      toxic effect is discussed: a direct toxicity of Paclitaxel or of its solvent
      (polyoxethylated castor oil), and the role of a pre-existing alteration of the
      blood-brain barrier.

PMID- 16604030
TI  - [Spontaneous pneumomediastinum in young adults: a benign clinical entity].
AB  - INTRODUCTION: Spontaneous pneumomediastinum is a little known cause of chest pain
      in young adults. The prognosis is invariably good. CASE REPORT: The authors
      report two cases of spontaneous pneumomediastinum with different aetiologies
      developing in young adults. The first occurred during strenuous sport and the
      second during an asthma attack. CONCLUSION: The discussion stresses the frequency
      of this condition in young men, its pathogenesis and natural history. In
      particular the authors draw on the current scientific data to explain the absence
      of predisposing factors and the extreme rarity of relapse of this benign
      disorder. Poor acquaintance with this clinical entity may lead to unnecessary
      diagnostic and therapeutic actions. The authors suggest a guideline for the
      management of this disorder.

PMID- 16604031
TI  - [Co-infection with Mycobacterium tuberculosis and Pneumocystis jiroveci in a
      patient without HIV infection].
AB  - INTRODUCTION: Co-infection with Pneumocystis jiroveci and Mycobacterium
      tuberculosis is rarely reported in patients without HIV infection. CASE REPORT:
      We report the case of a 30 year old woman admitted to hospital for respiratory
      distress associated with a diffuse infiltrative pneumopathy. Corticosteroid
      therapy had been started two months earlier for suspected pulmonary sarcoidosis.
      Fibreoptic bronchoscopy and broncho-alveolar lavage produced evidence of
      Mycobacterium tuberculosis and cysts of Pneumocystis jiroveci. HIV serology was
      negative. Clinical progress was satisfactory following anti-tuberculous and anti
      fungal therapy. CONCLUSION: Pneumocystis pneumonia is rare in subjects without
      HIV infection and is most often associated with a pathology or treatment leading
      to depression of cellular immunity. Corticosteroid treatment, even of short
      duration, presents the greatest risk. Systematic antibiotic prophylaxis should be
      considered in relation to the immune status of the patient. Co-infection with the
      tubercle bacillus as reported here is exceptionally rare.

PMID- 16604032
TI  - [Anomalous pulmonary venous drainage presenting as localised pulmonary oedema].

PMID- 16604033
TI  - [Allergic broncho-pulmonary aspergillosis treated with voriconazole].

PMID- 16604034
TI  - [Pseudomonas and the lung].

PMID- 16604035
TI  - [Tuberculous pneumothorax. Retrospective study of 23 cases in Tunisia].
AB  - The tubercular pneumothorax is a rare and severe form of tuberculosis which
      persists in Tunisia. We reviewed retrospectively our experience at the Pneumology
      Allergology Department of the Sousse Hospital with 23 cases of tubercular
      pneumothorax observed between 1985 and 2003. The suggestive symptom,
      pneumothorax, always occurred within a context poor general health and fever. The
      chest roentgengraph showed pneumothorax (n=8) or hydropneumothorax (n=15), and
      pulmonary lesions associated in 82.5% of patients. Bacteriological proof was
      obtained in 21 cases; in the two other patients, histological examination of the
      surgical specimen was highly suggestive of tuberculosis. Treatment associated
      antitubercular chemotherapy in compliance with the National Plan of against
      Tuberculosis (n=23), chest drainage (n=21) and respiratory physiotherapy (n=18).
      Five patients underwent surgery: pleural decortications (n=3), pulmonary
      resections (n=2). Two were lost to follow-up. The course was favourable in 78% of
      patients; there were two cases of partitioned pyopneumothorax and one post
      operative death. In our experience, tubercular pneumothorax was always associated
      with active cavitated tuberculosis. The course was almost favorable with
      antitubercular chemotherapy and chest drainage.

PMID- 16604036
TI  - [Perioperative smoking: expert conclusion (The SFAR 2005 Meeting, September 23,
      2005)].

PMID- 16604037
TI  - [Abundant hemothorax revealing extralobular pulmonary sequestration].
AB  - Hemothorax is an exceptional, serious and misleading manifestation of
      extralobular sequestration. We report the case of a 15-year-old patient who
      consulted for chest pain and sudden onset dyspnea. The chest x-ray revealed fluid
      pleural effusion. Pleural puncture produced a bloody fluid and the angioscan
      showed a hyperdense formation without a systemic artery. Thoracotomy was
      performed. A left intrapleural pyramidal formation vascularized with a pedicle
      from the thoracic aorta was identified and sequestrectomy performed. At two
      years, the patient has remained symptom free. Extralobular sequestration is an
      exceptional cause of hemothorax. The absence of an aberrant systemic vessel on
      the angioscan should not rule out the diagnosis of sequestration. Precautions
      must be taken at surgery to avoid vessel damage.

PMID- 16604038
TI  - [Spontaneous hemothorax: a rare but serious complication of intralobular
      pulmonary sequestration].
AB  - Pulmonary sequestration is a rare congenital malformation characterized by a non
      functional portion of pulmonary parenchyma devoid of any connection with the
      bronchial tree and pulmonary artery. If not identified antenatally or at birth,
      the sequestration may not be discovered until complications, mainly repeated
      infections, arise. Hemorrhage is another but much rarer complication which is
      generally severe. We report a new case of intralobular pulmonary sequestration
      revealed by hemoptysis then massive hemothroax with shock requiring emergency
      thoracotomy for hemostasis.

PMID- 16604039
TI  - [Acute airway obstruction during chemotherapy-induced agranulocytosis with
      fever].
AB  - Acute airway obstruction caused by mucoid impaction can cause sometimes life
      threatening respiratory distress. Bronchial plugging is usually observed in
      subjects with chronic diseases such as asthma, allergic bronchopulmonary
      aspergillosis, or cystic fibrosis. In children, it can be related to heart
      failure. Acute airway obstruction in a patient without a chronic respiratory
      disease is exceptional. We report the case of a patient who developed bronchial
      plugs obstructing the bronchi during a period of agranulocytosis induced by
      chemotherapy. The patient experienced acute respiratory distress with asphyxia.
      The plugs were composed of fibrin and required several fibroscopic procedures for
      clearance. To our knowledge, this is the first case report of acute airway
      obstruction by plugging during a period of agranulocytosis.

PMID- 16604040
TI  - [Pulmonary mucormycosis. Two cases].
AB  - Mucormycosis is a rare, devastating, opportunistic fungal infection, which occurs
      principally in some particular conditions, specially in non-controlled diabetic
      patients, notably during keratoacidosis. We report two cases in 62 and 72 year
      old diabetic women. In both cases, histologic examination of endobronchial
      biopsies showed tissue invasion by hyphae with characteristic morphology leading
      to the diagnosis of pulmonary zygomycosis. This difficult diagnosis must be
      evoked in diabetic patients with non-responsive lung infections in order to apply
      early aggressive therapy.

PMID- 16604041
TI  - [Intra-alveolar hemorrhage revealing pheochromocytoma].
AB  - We report a case of pheochromocytoma revealed by alveolar hemorrhage in a 51-year
      old woman. Pheochromocytomas are rare tumors deriving from the chromaffin tissue,
      and which clinical manifestations are highly variable, mostly unspecific, and
      very rarely concern the lung. Therefore, the diagnosis is often missed or
      delayed. However, without correct diagnosis and subsequently adapted treatment,
      the disease may be fatal. Thus, clinicians should be aware of the possible
      diagnosis of pheochromocytoma in patients presenting hemoptysis of an unknown
      origin.

PMID- 16604042
TI  - [A rare cause of superior vena cava thrombosis: pulmonary arteriovenous
      malformations].

PMID- 16604043
TI  - [Lung metastases of a small round cell desmoplastic tumor].

PMID- 16604044
TI  - [Tuberculosis of the thoracic wall].

PMID- 16604046
TI  - [Examination of formula for enhanced dynamic wedge factors in half fields].
AB  - The method presented by Liu et al. in 1998 has generally been used in Japan to
      calculate the wedge factor of the enhanced dynamic wedge (EDW). When the points
      used to evaluate the dose exist outside the central beam axis in the half field
      (HF), however, a difference of about 3% can occur between the values calculated
      by this method and the measured values. In 2003, Liu et al. presented a new
      general formula for calculating MU using the EDW. We modified the formula for
      calculating the wedge factor by combining the conventional calculation formula
      and the formula of Liu et al., presented in 2003, and compared the calculated
      values of the wedge factor of the EDW in the HF with the measured values. Our
      formula employs a very simple method in which only the normalized golden
      segmented treatment table (NGSTT) on the center of the radiation field and the
      central beam axis are added to the existing formula. The values calculated by our
      formula and the measured values were consistent within 1% in most combinations of
      energy, wedge angle, and size of radiation field. When the EDW was used for
      irradiation to the tangent line of the HF breast, in particular, the values
      calculated by our formula and the measured values were consistent within 0.5%,
      and it was possible to calculate the wedge factor with a higher degree of
      accuracy than that calculated with the existing formula.

PMID- 16604047
TI  - [Response by visual stimulation with the BOLD effect and motion artifact:
      identification of the activating signal and motion artifact].
AB  - This study used functional magnetic resonance imaging (fMRI) to evaluate brain
      function. fMRI data were collected by a block paradigm, and brain function was
      evaluated. However, irrelevant artifacts caused by the BOLD effect frequently
      occur in analytical processing. Therefore, there is a limit to obtaining an
      adequate activating reaction in the analytical system, which is normally equipped
      with MRI. However, there is a limit to obtaining a sufficient activating reaction
      in the analytical system, which is normally equipped with MRI. It has become
      standard practice to use an analytical system such as statistical parametric
      mapping (SPM). The response of movement of cerebrospinal fluid (CSF) artifact is
      high. Therefore, disappearance of the CSF artifact was done by statistical
      analysis. Then, the response of the signal from the beginning of stimulation was
      examined. As a result, the activating signal and the artifact signal could be
      identified.

PMID- 16604048
TI  - [Image quality and detection performance of a direct digital radiography system].
AB  - The physical characteristics of a direct amorphous Selenium (a-Se) digital
      fluoroscopy and radiography system were investigated. Pre-sampled modulation
      transfer functions (MTF) were measured using a slit method. Noise power spectra
      were determined for different input exposures by fast Fourier transform of
      uniformly exposed samples. The MTFs of direct digital radiography systems showed
      significantly higher values than those of indirect digital radiography and screen
      film systems. The direct digital radiography systems showed higher noise levels
      compared with those of indirect systems under roughly the same exposure
      conditions. Contrast-detail analysis was performed to compare detection by direct
      digital radiography systems with that of the screen-film (FUJI HG-M2/UR2)
      systems. The average contrast-detail curves of digital and film images were
      obtained from the results of observation. Image quality figures (IQF) were also
      calculated from the individual observer performance tests. The results indicated
      that digital contrast-detail curves and IQF are, on average, are equal those of
      the screen-film system.

PMID- 16604049
TI  - [Study of spatial resolution in three-dimensional rotational angiography].
AB  - In interventional radiology (IVR) of cerebral aneurysms, it is important to
      understand the form and physical relationships between the cerebral aneurysm and
      the surrounding vessels. However, because the vessels in the head area are highly
      complex, it can be difficult to comprehend the structure using conventional
      angiography. Therefore, three-dimensional rotational angiography (3D-RA) has been
      used in recent years. This article discusses studies of the spatial resolution of
      3D-RA. We reconstructed 3D-RA of an acrylic slit phantom (slit widths: 0.5, 0.75,
      1.0, 1.5 mm) and examined spatial resolution by visual evaluation and profile
      curves. When the slit phantom was arranged to avoid the effect of beam hardening,
      the spatial resolution of 3D-RA was found to be as high as 0.75 mm. When the slit
      phantom was placed orthogonal to the rotational axis of the C-arm, the spatial
      resolution of 3D-RA was decreased because of the cone angle effect of X-rays.
      However, it was considered within the allowable range for clinical study.
      Consequently, 3D-RA is valuable in IVR.

PMID- 16604050
TI  - [Examination of incident angle for photography of axial projection of zygomatic
      arch].
AB  - In axial zygomatic arch roentgenography, the radiographic angle is determined by
      taking account of the light field-projected image. However, this method is
      technically difficult and has poor reproducibility because the body target
      surface is uncertain at the time of positioning. Therefore, we obtained 3D-CT
      images from CT examinations of the facial or paranasal sinus, and we assessed the
      X-ray beam angle where the zygomatic arch is most clearly delineated in terms of
      sex and age by taking the acanthion-meatal line (France horizon) as the
      reference. The zygomatic arch was most clearly seen when the X-ray beam angle was
      perpendicular to the acanthion-meatal line. Excellent images were obtained, and
      reproducibility of the images was improved using the radiographic technique based
      on this result.

PMID- 16604051
TI  - [Algorithm for automatic determination of the sagittal imaging plane in lumbar
      MRI].

PMID- 16604052
TI  - The cleavage plane of corneal epithelial adhesion complex in traumatic recurrent
      corneal erosion.
AB  - PURPOSE: To determine the anatomic cleavage plane of the corneal epithelial
      adhesion complex in eyes with traumatic recurrent corneal erosion (RCE). METHODS:
      A loosened sheet of corneal epithelium was obtained from corneal epithelial
      wounds in eight patients with traumatic RCE, before each patient underwent
      phototherapeutic keratectomy. Three control groups were employed in the study,
      including normal corneal epithelial sheets obtained by mechanical separation,
      normal corneal tissues obtained by partial lamellar keratectomy during pterygial
      surgery, and corneal tissues from three residual corneoscleral rims of corneas
      donated for transplantation. Immunofluorescence staining was performed using
      monoclonal antibodies against integrins beta1 and beta4, laminin 5, and collagen
      VII to identify abnormalities in specific layers of the adhesion complex.
      RESULTS: In both experimental and control specimens, the suprabasal and basal
      cells stained positive for integrin beta1, and basal cells stained positive for
      integrin beta4. Similarly, a continuous line along the base of each epithelial
      sheet and each control specimen stained positive for laminin 5, a major basement
      membrane component. In contrast, in all controls there was a continuous linear
      staining pattern along the basement membrane of stain positive for collagen VII,
      a marker for the presence of fibrils that anchor corneal basement membrane to
      Bowman's layer, but epithelial sheets from eyes with RCE showed either a
      discontinuous line stained positive for collagen VII (three out of eight
      specimens) or no positively stained areas (five out of eight specimens). The
      results indicated the cleavage plane of RCE was located at collagen VII layer,
      between basement membrane and Bowman's layer. CONCLUSIONS: This study identified
      a defect in collagen fibrils that anchor the corneal epithelium basement membrane
      to Bowman's layer as the cause of corneal epithelial loss in cases of traumatic
      RCE. As hemidesmosomes do not seem to be impaired, a treatment specific to
      restore anchoring fibril function might prove helpful.

PMID- 16604053
TI  - Carnosine inhibits modifications and decreased molecular chaperone activity of
      lens alpha-crystallin induced by ribose and fructose 6-phosphate.
AB  - PURPOSE: Alpha-crystallin, a major structural protein in the lens, prevents heat-
      and oxidative stress-induced aggregation of proteins and inactivation of enzymes
      by acting as a molecular chaperone. Modification of alpha-crystallin by some
      posttranslational modifications results in conformational changes and decreases
      in chaperone activity, which may contribute to cataractogenesis in vivo.
      Carnosine (beta-alanyl-L-histidine), an endogenous histidine dipeptide, prevents
      protein modifications including glycation and oxidation. The purpose of this
      study was to further explore whether carnosine can protect alpha-crystallin
      against glycation by a sugar and a sugar phosphate, and in particular to find
      whether it can protect against its decreased chaperone activity. Additionally, we
      investigated whether carnosine could directly react with a sugar and a sugar
      phosphate. METHODS: Bovine lens alphaL-crystallin was separated by size-exclusion
      chromatography on a Sephacryl S-300 HR column. alphaL-crystallin was incubated
      with different concentrations of fructose 6-phosphate (F6P) and ribose with or
      without carnosine for different times. The chaperone activity of alphaL
      crystallin was monitored using the prevention of thermal aggregation of betaL
      crystallin. The modified alphaL-crystallin was examined by SDS-PAGE and
      fluorescence measurements. The absorbance spectra of solutions of carnosine and
      sugars were investigated. RESULTS: Carnosine inhibited the crosslinking of alphaL
      crystallin induced by F6P and ribose in a dose- and time-dependent manner. It
      protected alphaL-crystallin against its decreased chaperone activity induced by
      100 mM F6P during four days incubation, but not against ribose-induced change.
      Control alphaL-crystallin gave 96% protection against aggregation of betaL
      crystallin after four days incubation, but only 85% protection was achieved in
      the presence of F6P, rising to 96% (p=0.0004) in the presence of carnosine. After
      more extensive modification by sugar and a sugar phosphate, there was no
      significant protective effect of carnosine on alphaL-crystallin cross-linking or
      chaperone activity. The tryptophan fluorescence of modified alphaL-crystallin was
      remarkably decreased in the presence of F6P and ribose. However, the decrease was
      less when 50 mM carnosine was present during eight days incubation with F6P.
      Carnosine did not maintain the fluorescence when ribose was used. The
      nontryptophan fluorescence was increased with a shift to longer wavelengths in a
      time-dependent manner. Carnosine readily reacted with F6P and ribose thereby
      inhibiting glycation-mediated protein modification as revealed
      electrophoretically. The increased absorbance was time-dependent, suggesting
      adducts may be formed between F6P, ribose, and carnosine. CONCLUSIONS: This is
      the first report showing that carnosine can protect the chaperone activity of
      alpha-crystallin. This chaperone may protect against cataractous changes. In
      addition to demonstrating the effects of carnosine on prevention crosslinking,
      our studies also bring out important evidence that carnosine reacts with F6P and
      ribose, which suggests carnosine's potential as a possible nontoxic modulator of
      diabetic complications.

PMID- 16604054
TI  - Circadian clockwork machinery in neural retina: evidence for the presence of
      functional clock components in photoreceptor-enriched chick retinal cell
      cultures.
AB  - PURPOSE: Circadian clocks in retinas regulate a variety of biochemical and
      physiological processes. Retinal neurons, particularly photoreceptor cells, are
      thought to contain autonomous circadian clocks that control iodopsin expression,
      cFos expression, cAMP levels, and melatonin synthesis. Photoreceptor-enriched
      cell cultures prepared from chick embryo retina and entrained to a daily light
      dark (LD) cycle exhibit circadian rhythms of cAMP levels and the activity of
      arylalkylamine N-acetyltransferase (AANAT), a key regulatory enzyme in melatonin
      synthesis. The present study was conducted to investigate the expression of
      circadian clockwork machinery comprised of clock genes; a clock-controlled gene,
      Aanat; and a clock output, melatonin, in the photoreceptor-enriched cultured
      retinal cells. METHODS: Photoreceptor-enriched cell cultures were prepared from
      E6 neural retinas and incubated under 14 h:10 h light-dark cycle (LD) of
      illumination for 8 days and then transferred to constant (24 h/day) darkness
      (DD). Cells were collected every 4 h in LD and DD, and RNA was isolated. cDNA was
      prepared from each sample and transcripts of clock genes and Aanat were measured
      using real-time polymerase chain reaction (PCR). Melatonin release into the
      culture medium was assayed by HPLC with fluorescence detection at intervals of 3
      h in LD and DD. RESULTS: Cultured neural retina cells exposed to a light-dark
      cycle showed rhythmic expression of clock genes. Bmal1 and Npas2 (also known as
      Mop4) peaked late in the day in LD and in DD. Clock mRNA was high at night in LD,
      but arrhythmic in DD. Cry1 and Per2 transcripts increased rapidly in the early
      morning and were low at night. The rhythm of Per2 was reduced in amplitude in
      constant darkness (DD). Levels of Cry1 and Per2 transcripts were stimulated by
      light exposure at night. Melatonin release and Aanat mRNA were low during the day
      and high at night. Rhythmic expression of clock genes and Aanat was not observed
      in cultures not exposed to a LD cycle but treated otherwise identically to
      cultures described above. CONCLUSIONS: Photoreceptor-enriched cell cultures
      derived from chick embryo neural retina contain a complete circadian clockwork
      system that is entrained by the light-dark cycle, and has a core timekeeping
      mechanism and circadian output in the form of melatonin synthesis.

PMID- 16604055
TI  - Macular and peripheral distribution of ICAM-1 in the human choriocapillaris and
      retina.
AB  - PURPOSE: In order to understand the extent of choriocapillary endothelial cell
      activation in different topographic regions of the eye, we sought to compare the
      localization of intercellular adhesion molecule-1 (ICAM-1) in macular and
      peripheral regions of human eyes. METHODS: Sections of sucrose-embedded human
      donor eyes that included the macula and ora serrata were evaluated for ICAM-1 and
      ICAM-2 immunoreactivity with monoclonal and polyclonal antibodies. Patterns of
      ICAM-1 labeling in peripheral and macular regions were examined in 20 eyes.
      Morphometric analyses of anti-ICAM-1 labeling intensity in the choriocapillaris
      were performed using ImageJ software on a series of macular and extramacular
      punches from nine eyes. Quantitative PCR analysis for ICAM-1 mRNA was performed
      on the RPE-choroid from the same regions from six of the same eyes, and Western
      blots of samples treated or untreated with N-glycosidase were performed to
      compare retinal and choroidal ICAM-1. RESULTS: ICAM-1 labeling of the
      choriocapillaris was typically more intense in the macula than in the peripheral
      choroid in human donor eyes (14/20). ICAM-2 was also detected in the
      choriocapillaris and retinal vessels. Morphometric measurements confirmed a
      significant macular-extramacular difference in ICAM-1 in six of nine eyes
      (p<0.05), with 1 of 9 eyes showing the opposite pattern. This pattern was not
      noted for endogenous alkaline phosphatase or ICAM-2. The opposite pattern was
      noted in the external limiting membrane (ELM), which exhibited more intense ICAM
      1 labeling in the far periphery than in the macula. On Western blots, choroidal
      ICAM-1 exhibited a greater molecular weight than the retinal form, with most of
      the apparent weight difference due to N-linked carbohydrate chains. CONCLUSIONS:
      The regional differences in ICAM-1 distribution in the choriocapillaris may
      indicate that this region is subject to increased leukocyte trafficking. In view
      of the role of inflammatory processes in age-related macular degeneration (AMD),
      we propose that the higher level of ICAM-1 protein in the macular
      choriocapillaris may impart greater susceptibility of the macula to immune cell
      mediated damage in AMD.

PMID- 16604056
TI  - PAX6 missense mutations associated in patients with optic nerve malformation.
AB  - PURPOSE: PAX6 missense mutations are likely to cause a spectrum of ocular,
      neurological, and systemic developmental defects and have been reported in
      various ethnic groups. The purpose of this study was to investigate the clinical
      features of optic nerve malformation caused by PAX6 mutations in Indian patients.
      METHODS: Total genomic DNA was isolated from peripheral blood of 27 sporadic
      probands affected with congenital optic nerve malformation, unaffected family
      members, and 50 unrelated age-matched controls. Informed consent was obtained
      from all study subjects. Polymerase chain reaction was carried out to explore
      PAX6 defective alleles using single-strand conformation analysis (PCR-SSCA)
      followed by automated bidirectional sequencing. RESULTS: We identified two novel
      PAX6 missense mutations in two unrelated sporadic probands. The mutation analysis
      revealed variation at position c.469G>C, codon 36 in proband ONH 4-1 with optic
      nerve hypoplasia. The other de novo mutation was observed at c.514G>C, codon 51
      in proband ODC 5-1 with optic disc coloboma. Both G>C base substitutions cause a
      relatively conservative amino acid change, altering glycine to alanine residues
      within the paired DNA-binding domain. CONCLUSIONS: In this study, we have been
      able to identify two sequence variations in the PAX6 gene. These missense
      mutations may uniquely alter the structure and expression of PAX6 protein,
      resulting in distinct clinical phenotypes. Mutation analysis of 27 probands for
      PAX6 has resulted in only two significant variants. This finding demonstrated
      that the frequency of PAX6 mutations associated with optic nerve malformation is
      low, requiring the elucidation of other candidate genes in other patients.

PMID- 16604057
TI  - Postnatal development of myosin heavy chain isoforms in rat extraocular muscles.
AB  - PURPOSE: To determine the composition of myosin heavy chain (MHC) isoforms in rat
      extraocular muscles (EOMs) during postnatal development. METHODS: The MHC
      composition of rat EOMs at postnatal day 0 (P0), postnatal day 14 (P14), and
      adults was evaluated at mRNA levels by competitive polymerase chain reaction and
      MHC composition of each six EOM in adult rats. RESULTS: EOMs at P0 revealed
      predominant expression of neonatal MHC (75.5%) with a lesser percentage of
      embryonic MHC (12.8%) and 2A MHC (11.5%). 2X MHC was expressed at low levels and
      other MHC isoforms were not detected. At P14, EOMs expressed mostly 2X MHC
      (42.4%) and 2A MHC (27.4%). Expression levels of neonatal MHC (14.1%) and
      embryonic MHC (4.9%) decreased. 2B MHC (8.2%), EOM MHC (1.9%), and beta-cardiac
      MHC (1.1%) were detected at low levels. In the adult rats, EOMs contained over
      80% of three fast MHC isoforms, such as 2X MHC (29.9%), 2A MHC (29.3%), and 2B
      MHC (24.5%). Each of six adult EOM showed slightly different expression levels of
      MHC composition. CONCLUSIONS: A strong correlation exists between the composition
      of fast MHC isoforms and muscle development. MHC isoform followed a neonatal MHC
      2X MHC-2B MHC isoform switching pattern after birth. Postnatal development of
      EOMs had a slightly different expression pattern for MHC isoforms and may have
      different regulatory roles related to their functional requirement.

PMID- 16604058
TI  - Novel mutations in GJA8 associated with autosomal dominant congenital cataract
      and microcornea.
AB  - PURPOSE: The purpose of this study was to estimate the importance of mutations in
      the connexin50 gene (GJA8) as a cause of congenital or developmental cataracts in
      the Indian population and to identify novel mutations in GJA8 that cause cataract
      in this population. METHODS: The coding region of GJA8 was analyzed for mutation
      by single strand conformational polymorphism in 60 probands affected with
      congenital or developmental cataract of which 11 probands' corneal diameter
      measured less than 11.00 mm. Direct sequencing was performed for samples that
      displayed an abnormal electrophoresis pattern. The segregation of the change with
      the diseased phenotype was analyzed in the entire pedigree by restriction
      fragment length polymorphism (RFLP) analysis. RESULTS: Molecular analysis of GJA8
      revealed two novel missense mutations V44E and R198Q, in the population screened.
      The mutations cosegregated with the diseased phenotype in an autosomal dominant
      manner and were absent in 400 normal control chromosomes analyzed. GJA8 mutations
      were seen in two of the 60 unrelated probands with cataracts. Affected
      individuals in both of whose families also had microcornea and variable myopia.
      CONCLUSIONS: This is the first report of mutations in GJA8 to be associated with
      autosomal dominant cataract and microcornea. Mutations in GJA8 cause 3.3% of
      congenital cataracts in the population of India.

PMID- 16604059
TI  - Herpes simplex virus 1 (HSV-1) for cancer treatment.
AB  - Cancer remains a serious threat to human health, causing over 500 000 deaths each
      year in US alone, exceeded only by heart diseases. Many new technologies are
      being developed to fight cancer, among which are gene therapies and oncolytic
      virotherapies. Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus
      with many favorable properties both as a delivery vector for cancer therapeutic
      genes and as a backbone for oncolytic viruses. Herpes simplex virus type 1 is
      highly infectious, so HSV-1 vectors are efficient vehicles for the delivery of
      exogenous genetic materials to cells. The inherent cytotoxicity of this virus, if
      harnessed and made to be selective by genetic manipulations, makes this virus a
      good candidate for developing viral oncolytic approach. Furthermore, its large
      genome size, ability to infect cells with a high degree of efficiency, and the
      presence of an inherent replication controlling mechanism, the thymidine kinase
      gene, add to its potential capabilities. This review briefly summarizes the
      biology of HSV-1, examines various strategies that have been used to genetically
      modify the virus, and discusses preclinical as well as clinical results of the
      HSV-1-derived vectors in cancer treatment.

PMID- 16604060
TI  - Preventing gene silencing with human replicators.
AB  - Transcriptional silencing, one of the major impediments to gene therapy in
      humans, is often accompanied by replication during late S-phase. We report that
      transcriptional silencing and late replication were prevented by DNA sequences
      that can initiate DNA replication (replicators). When replicators were included
      in silencing-prone transgenes, they did not undergo transcriptional silencing,
      replicated early and maintained histone acetylation patterns characteristic of
      euchromatin. A mutant replicator, which could not initiate replication, could not
      prevent gene silencing and replicated late when included in identical transgenes
      and inserted at identical locations. These observations suggest that replicators
      introduce epigenetic chromatin changes that facilitate initiation of DNA
      replication and affect gene silencing. Inclusion of functional replicators in
      gene therapy vectors may provide a tool for stabilizing gene expression patterns.

PMID- 16604061
TI  - The thioredoxin-related redox-regulating protein nucleoredoxin inhibits Wnt-beta
      catenin signalling through dishevelled.
AB  - Dishevelled (Dvl) transduces signals from the Wnt receptor, Frizzled, to
      downstream components, leading to the stabilization of beta-catenin and
      subsequent activation of the transcription factor T cell factor (TCF) and/or
      lymphoid enchancer factor (LEF). However, the mechanism of Dvl action remains
      unclear. Here, we report that nucleoredoxin (NRX), a thioredoxin (TRX) family
      protein, interacts with Dvl. Overexpression of NRX selectively suppresses the Wnt
      beta-catenin pathway and ablation of NRX by RNA-interference (RNAi) results in
      activation of TCF, accelerated cell proliferation and enhancement of oncogenicity
      through cooperation with mitogen-activated extracellular signal regulated kinase
      kinase (MEK) or Ras. We find that cells respond to H(2)O(2) stimulation by
      activating TCF. Redox-dependent activation of the Wnt-beta-catenin pathway occurs
      independently of extracellular Wnts and is impaired by RNAi of NRX . In addition,
      association between Dvl and NRX is inhibited by H(2)O(2) treatment. These data
      suggest a relationship between the Wnt-beta-catenin pathway and redox signalling
      through redox-sensitive association of NRX with Dvl.

PMID- 16604062
TI  - A ubiquitin-interacting motif protects polyubiquitinated Met4 from degradation by
      the 26S proteasome.
AB  - Covalent attachment of ubiquitin to proteins regulates a host of cellular events
      by proteolysis dependent and independent mechanisms. A variety of protein domains
      that bind non-covalently to ubiquitin have been described and functionally linked
      to diverse cellular processes. Overall, however, the understanding and knowledge
      of the mechanisms by which ubiquitin-binding domains (UBDs) regulate these
      processes is limited. Here, we describe identification of a UBD in the yeast
      transcription factor Met4. Met4 activity, but not its stability, is regulated by
      polyubiquitination. We found that the UBD restricts the length of the
      polyubiquitin chain that is assembled on Met4, and prevents proteasomal
      recognition and degradation of polyubiquitinated Met4. Inactivation of the UBD
      allowed synthesis of longer ubiquitin chains on Met4 and transformed the normally
      stable polyubiquitinated Met4 into a short-lived protein. Our results demonstrate
      a function for UBDs in ubiquitin-chain synthesis and regulation of protein
      degradation.

PMID- 16604063
TI  - Syndecan-4 regulates non-canonical Wnt signalling and is essential for convergent
      and extension movements in Xenopus embryos.
AB  - Early shaping of Xenopus laevis embryos occurs through convergent and extension
      movements, a process that is driven by intercalation of polarized dorsal
      mesodermal cells and regulated by non-canonical Wnt signalling. Here, we have
      identified Xenopus syndecan-4 (xSyn4), a cell-surface transmembrane heparan
      sulphate proteoglycan. At the gastrula stage, xSyn4 is expressed in the
      involuting dorsal mesoderm and the anterior neuroectoderm. Later, it is found in
      the pronephros, branchial arches, brain and tailbud. Both gain- and loss-of
      function of xSyn4 impaired convergent extension movements in Xenopus embryos and
      in activin-treated ectodermal explants. xSyn4 interacts functionally and
      biochemically with the Wnt receptor Frizzled7 (xFz7) and its signal transducer
      Dishevelled (xDsh). Furthermore, xSyn4 is necessary and sufficient for
      translocation of xDsh to the plasma membrane - a landmark in the activation of
      non-canonical Wnt signalling. Our results suggest that the ability of xSyn4 to
      translocate xDsh is regulated by fibronectin, a component of the extracellular
      matrix required for proper convergent extension movements. We propose a model
      where xSyn4 and fibronectin cooperate with xFz7 and Wnt in the specific
      activation of the non-canonical Wnt pathway.

PMID- 16604064
TI  - Loss of the VHR dual-specific phosphatase causes cell-cycle arrest and
      senescence.
AB  - Protein tyrosine phosphatases regulate important processes in eukaryotic cells
      and have critical functions in many human diseases including diabetes to cancer.
      Here, we report that the human Vaccinia H1-related (VHR) dual-specific protein
      tyrosine phosphatase regulates cell-cycle progression and is itself modulated
      during the cell cycle. Using RNA interference (RNAi), we demonstrate that cells
      lacking VHR arrest at the G1-S and G2-M transitions of the cell cycle and show
      the initial signs of senescence, such as flattening, spreading, appearance of
      autophagosomes, beta-galactosidase staining and decreased telomerase activity. In
      agreement with this notion, cells lacking VHR were found to upregulate p21(Cip
      Waf1), whereas they downregulated the expression of genes for cell-cycle
      regulators, DNA replication, transcription and mRNA processing. Loss of VHR also
      caused a several-fold increase in serum-induced activation of its substrates, the
      mitogen-activated protein (MAP) kinases Jnk and Erk. VHR-induced cell-cycle
      arrest was dependent on this hyperactivation of Jnk and Erk, and was reversed by
      Jnk and Erk inhibition or knock-down. We conclude that VHR is required for cell
      cycle progression as it modulates MAP kinase activation in a cell-cycle phase
      dependent manner.

PMID- 16604065
TI  - Individual dimers of the mitotic kinesin motor Eg5 step processively and support
      substantial loads in vitro.
AB  - Eg5, a member of the kinesin superfamily of microtubule-based motors, is
      essential for bipolar spindle assembly and maintenance during mitosis, yet little
      is known about the mechanisms by which it accomplishes these tasks. Here, we used
      an automated optical trapping apparatus in conjunction with a novel motility
      assay that employed chemically modified surfaces to probe the mechanochemistry of
      Eg5. Individual dimers, formed by a recombinant human construct Eg5-513-5His,
      stepped processively along microtubules in 8-nm increments, with short run
      lengths averaging approximately eight steps. By varying the applied load (with a
      force clamp) and the ATP concentration, we found that the velocity of Eg5 was
      slower and less sensitive to external load than that of conventional kinesin,
      possibly reflecting the distinct demands of spindle assembly as compared with
      vesicle transport. The Eg5-513-5His velocity data were described by a minimal,
      three-state model where a force-dependent transition follows nucleotide binding.

PMID- 16604066
TI  - Atomic resolution crystallography reveals how changes in pH shape the protein
      microenvironment.
AB  - Hydrogen atoms are a vital component of enzyme structure and function. In recent
      years, atomic resolution crystallography (>or=1.2 A) has been successfully used
      to investigate the role of the hydrogen atom in enzymatic catalysis. Here, atomic
      resolution crystallography was used to study the effect of pH on cholesterol
      oxidase from Streptomyces sp., a flavoenzyme oxidoreductase. Crystallographic
      observations of the anionic oxidized flavin cofactor at basic pH are consistent
      with the UV-visible absorption profile of the enzyme and readily explain the
      reversible pH-dependent loss of oxidation activity. Furthermore, a hydrogen atom,
      positioned at an unusually short distance from the main chain carbonyl oxygen of
      Met122 at high pH, was observed, suggesting a previously unknown mechanism of
      cofactor stabilization. This study shows how a redox active site responds to
      changes in the enzyme's environment and how these changes are able to influence
      the mechanism of enzymatic catalysis.

PMID- 16604067
TI  - A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC
      17 and synaptobrevin/SNB-1 in C. elegans.
AB  - Acetylcholine, a major excitatory neurotransmitter in Caenorhabditis elegans, is
      transported into synaptic vesicles by the vesicular acetylcholine transporter
      encoded by unc-17. The abnormal behavior of unc-17(e245) mutants, which have a
      glycine-to-arginine substitution in a transmembrane domain, is markedly improved
      by a mutant synaptobrevin with an isoleucine-to-aspartate substitution in its
      transmembrane domain. These results suggest an association of vesicular soluble N
      ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) components
      with vesicular neurotransmitter transporters.

PMID- 16604068
TI  - The development of direction selectivity in ferret visual cortex requires early
      visual experience.
AB  - Development of the selective response properties that define columns in sensory
      cortex is thought to begin early in cortical maturation, without the need for
      experience. We investigated the development of direction selectivity in ferret
      visual cortex using optical imaging and electrophysiological techniques and found
      an exception to this view. Unlike orientation selectivity and ocular dominance,
      direction selectivity was not detected at eye opening. Direction selectivity
      emerged several days later and strengthened to adult levels over the following 2
      weeks. Visual experience was essential for this process, as shown by the absence
      of direction selectivity in dark-reared ferrets. The impairment persisted in dark
      reared ferrets that were given experience after this period, despite the recovery
      of response amplitude, preference and bandwidth for stimulus orientation, spatial
      and temporal frequency, and contrast. Visual experience in early postnatal life
      plays a necessary and unique role in the development of cortical direction
      selectivity.

PMID- 16604070
TI  - Distinct modes of regulated receptor insertion to the somatodendritic plasma
      membrane.
AB  - Many neural signaling receptors are regulated by endocytosis, but little is known
      about receptor insertion into the plasma membrane. Time-lapse imaging of the
      beta2 adrenergic receptor expressed in cultured rat hippocampal neurons, using pH
      sensitive green fluorescent protein tagging and total internal reflection
      fluorescence microscopy, resolved distinct vesicular fusion events mediating
      receptor insertion into the somatodendritic plasma membrane. A 'transient'
      insertion mode resulted in rapid lateral dispersion of receptors immediately
      after insertion. A 'persistent' insertion mode resulted in the retention of
      inserted receptors in surface-accessible domains, which were relatively immobile
      for a prolonged 'wait' period before dispersing laterally. Distinct insertion
      modes were oppositely regulated by receptor activation and by mechanisms
      differing in their dependence on the signaling effector cyclic AMP-dependent
      protein kinase. These results reveal a new mechanism for homeostatic regulation
      of postsynaptic signaling and a 'kiss-and-wait' mode of regulated membrane
      protein insertion in neurons.

PMID- 16604069
TI  - Microstimulation of macaque area LIP affects decision-making in a motion
      discrimination task.
AB  - A central goal of cognitive neuroscience is to elucidate the neural mechanisms
      underlying decision-making. Recent physiological studies suggest that neurons in
      association areas may be involved in this process. To test this, we measured the
      effects of electrical microstimulation in the lateral intraparietal area (LIP)
      while monkeys performed a reaction-time motion discrimination task with a
      saccadic response. In each experiment, we identified a cluster of LIP cells with
      overlapping response fields (RFs) and sustained activity during memory-guided
      saccades. Microstimulation of this cluster caused an increase in the proportion
      of choices toward the RF of the stimulated neurons. Choices toward the stimulated
      RF were faster with microstimulation, while choices in the opposite direction
      were slower. Microstimulation never directly evoked saccades, nor did it change
      reaction times in a simple saccade task. These results demonstrate that the
      discharge of LIP neurons is causally related to decision formation in the
      discrimination task.

PMID- 16604071
TI  - X-linked Cornelia de Lange syndrome owing to SMC1L1 mutations.
AB  - Cornelia de Lange syndrome is a multisystem developmental disorder characterized
      by facial dysmorphisms, upper limb abnormalities, growth delay and cognitive
      retardation. Mutations in the NIPBL gene, a component of the cohesin complex,
      account for approximately half of the affected individuals. We report here that
      mutations in SMC1L1 (also known as SMC1), which encodes a different subunit of
      the cohesin complex, are responsible for CdLS in three male members of an
      affected family and in one sporadic case.

PMID- 16604072
TI  - Mitochondrial DNA deletions are abundant and cause functional impairment in aged
      human substantia nigra neurons.
AB  - Using a novel single-molecule PCR approach to quantify the total burden of
      mitochondrial DNA (mtDNA) molecules with deletions, we show that a high
      proportion of individual pigmented neurons in the aged human substantia nigra
      contain very high levels of mtDNA deletions. Molecules with deletions are largely
      clonal within each neuron; that is, they originate from a single deleted mtDNA
      molecule that has expanded clonally. The fraction of mtDNA deletions is
      significantly higher in cytochrome c oxidase (COX)-deficient neurons than in COX
      positive neurons, suggesting that mtDNA deletions may be directly responsible for
      impaired cellular respiration.

PMID- 16604073
TI  - Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin
      expression.
AB  - Hepcidin is a key regulator of systemic iron homeostasis. Hepcidin deficiency
      induces iron overload, whereas hepcidin excess induces anemia. Mutations in the
      gene encoding hemojuvelin (HFE2, also known as HJV) cause severe iron overload
      and correlate with low hepcidin levels, suggesting that hemojuvelin positively
      regulates hepcidin expression. Hemojuvelin is a member of the repulsive guidance
      molecule (RGM) family, which also includes the bone morphogenetic protein (BMP)
      coreceptors RGMA and DRAGON (RGMB). Here, we report that hemojuvelin is a BMP
      coreceptor and that hemojuvelin mutants associated with hemochromatosis have
      impaired BMP signaling ability. Furthermore, BMP upregulates hepatocyte hepcidin
      expression, a process enhanced by hemojuvelin and blunted in Hfe2-/- hepatocytes.
      Our data suggest a mechanism by which HFE2 mutations cause hemochromatosis:
      hemojuvelin dysfunction decreases BMP signaling, thereby lowering hepcidin
      expression.

PMID- 16604074
TI  - High levels of mitochondrial DNA deletions in substantia nigra neurons in aging
      and Parkinson disease.
AB  - Here we show that in substantia nigra neurons from both aged controls and
      individuals with Parkinson disease, there is a high level of deleted
      mitochondrial DNA (mtDNA) (controls, 43.3% +/- 9.3%; individuals with Parkinson
      disease, 52.3% +/- 9.3%). These mtDNA mutations are somatic, with different
      clonally expanded deletions in individual cells, and high levels of these
      mutations are associated with respiratory chain deficiency. Our studies suggest
      that somatic mtDNA deletions are important in the selective neuronal loss
      observed in brain aging and in Parkinson disease.

PMID- 16604076
TI  - The generation of protective memory-like CD8+ T cells during homeostatic
      proliferation requires CD4+ T cells.
AB  - Antigen-specific memory T cells are a critical component of protective immunity
      because of their increased frequency and enhanced reactivity after restimulation.
      However, it is unclear whether 'memory-like' T cells generated during lymphopenia
      induced homeostatic proliferation can also offer protection against pathogens.
      Here we show that homeostatic proliferation-induced memory (HP-memory) CD8(+) T
      cells controlled bacterial infection as effectively as 'true' memory CD8(+) T
      cells, but their protective capacity required the presence of CD4(+) T cells
      during homeostatic proliferation. The necessity for CD4 help was overcome,
      however, if the HP-memory CD8(+) T cells lacked expression of TRAIL (tumor
      necrosis factor-related apoptosis-inducing ligand; also called Apo-2L). Thus,
      like conventional CD8(+) memory T cells, the protective function of HP-memory
      CD8(+) T cells shows dependence on CD4(+) T cell help.

PMID- 16604077
TI  - Ultra-high-density phase-change storage and memory.
AB  - Phase-change storage is widely used in optical information technologies (DVD, CD
      ROM and so on), and recently it has also been considered for non-volatile memory
      applications. This work reports advances in thermal data recording of phase
      change materials. Specifically, we show erasable thermal phase-change recording
      at a storage density of 3.3 Tb inch(-2), which is three orders of magnitude
      denser than that currently achievable with commercial optical storage
      technologies. We demonstrate the concept of a thin-film nanoheater to realize
      ultra-small heat spots with dimensions of less than 50 nm. Finally, we show in a
      proof-of-concept demonstration that an individual thin-film heater can write,
      erase and read the phase of these storage materials at competitive speeds. This
      work provides important stepping stones for a very-high-density storage or memory
      technology based on phase-change materials.

PMID- 16604075
TI  - Osteopontin expression is essential for interferon-alpha production by
      plasmacytoid dendritic cells.
AB  - The observation that the T-bet transcription factor allows tissue-specific
      upregulation of intracellular osteopontin (Opn-i) in plasmacytoid dendritic cells
      (pDCs) suggests that Opn might contribute to the expression of interferon-alpha
      (IFN-alpha) in those cells. Here we show that Opn deficiency substantially
      reduced Toll-like receptor 9 (TLR9)-dependent IFN-alpha responses but spared
      expression of transcription factor NF-kappaB-dependent proinflammatory cytokines.
      Shortly after TLR9 engagement, colocalization of Opn-i and the adaptor molecule
      MyD88 was associated with induction of transcription factor IRF7-dependent IFN
      alpha gene expression, whereas deficient expression of Opn-i was associated with
      defective nuclear translocation of IRF7 in pDCs. The importance of the Opn-IFN
      alpha pathway was emphasized by its essential involvement in cross-presentation
      in vitro and in anti-herpes simplex virus 1 IFN-alpha response in vivo. The
      finding that Opn-i selectively coupled TLR9 signaling to expression of IFN-alpha
      but not to that of other proinflammatory cytokines provides new molecular insight
      into the biology of pDCs.

PMID- 16604078
TI  - Tensile stress and creep in thermally grown oxide.
AB  - Structural components that operate at high temperatures (for example, turbine
      blades) rely on thermally grown oxide (TGO), commonly alumina, for corrosion
      protection. Strains that develop in TGOs during operation can reduce the
      protectiveness of the TGO. However, the occurrence of growth strains in TGOs, and
      mechanisms that cause them, are poorly understood. It is accepted that
      compressive strains can develop as oxygen and metal atoms meet to form new growth
      within constrained oxide. More controversial is the experimental finding that
      large tensile stresses, close to 1 GPa, develop during isothermal growth
      conditions in alumina TGO formed on a FeCrAlY alloy. Using a novel technique
      based on synchrotron radiation, we have confirmed these previous results, and
      show that the tensile strain develops as the early oxide, (Fe,Cr,Al)(2)O(3),
      converts to alpha-Al2O3 during the growth process. This allows us to model the
      strain behaviour by including creep and this diffusion-controlled phase change.

PMID- 16604079
TI  - Going beyond the reflectance limit of cholesteric liquid crystals.
AB  - Cholesteric liquid-crystalline states of matter are abundant in nature:
      atherosclerosis, arthropod cuticles, condensed phases of DNA, plant cell walls,
      human compact bone osteon, and chiral biopolymers. The self-organized helical
      structure produces unique optical properties. Light is reflected when the
      wavelength matches the pitch (twice periodicity); cholesteric liquid crystals are
      not only coloured filters, but also reflectors and polarizers. But, in theory,
      the reflectance is limited to 50% of the ambient (unpolarized) light because
      circularly polarized light of the same handedness as the helix is reflected. Here
      we give details of a cholesteric medium for which the reflectance limit is
      exceeded. Photopolymerizable monomers are introduced into a cholesteric medium
      exhibiting a thermally induced helicity inversion, and the blend is then cured
      with ultraviolet light when the helix is right-handed. Because of memory effects
      attributable to the polymer network, the reflectance exceeds 50% when measured at
      the temperature assigned for a cholesteric helix with the same pitch but a left
      handed sense before the reaction. As cholesteric materials are used as tunable
      bandpass filters, reflectors or polarizers and temperature or pressure sensors,
      novel opportunities to modulate the reflection over the whole light flux range,
      instead of only 50%, are offered.

PMID- 16604080
TI  - Continuous-flow lithography for high-throughput microparticle synthesis.
AB  - Precisely shaped polymeric particles and structures are widely used for
      applications in photonic materials, MEMS, biomaterials and self-assembly. Current
      approaches for particle synthesis are either batch processes or flow-through
      microfluidic schemes that are based on two-phase systems, limiting the
      throughput, shape and functionality of the particles. We report a one-phase
      method that combines the advantages of microscope projection photolithography and
      microfluidics to continuously form morphologically complex or multifunctional
      particles down to the colloidal length scale. Exploiting the inhibition of free
      radical polymerization near PDMS surfaces, we are able to repeatedly pattern and
      flow rows of particles in less than 0.1 s, affording a throughput of near 100
      particles per second using the simplest of device designs. Polymerization was
      also carried out across laminar, co-flowing streams to generate Janus particles
      containing different chemistries, whose relative proportions could be easily
      tuned. This new high-throughput technique offers unprecedented control over
      particle size, shape and anisotropy.

PMID- 16604081
TI  - Elastically relaxed free-standing strained-silicon nanomembranes.
AB  - Strain plays a critical role in the properties of materials. In silicon and
      silicon-germanium, strain provides a mechanism for control of both carrier
      mobility and band offsets. In materials integration, strain is typically tuned
      through the use of dislocations and elemental composition. We demonstrate a
      versatile method to control strain by fabricating membranes in which the final
      strain state is controlled by elastic strain sharing, that is, without the
      formation of defects. We grow Si/SiGe layers on a substrate from which they can
      be released, forming nanomembranes. X-ray-diffraction measurements confirm a
      final strain predicted by elasticity theory. The effectiveness of elastic strain
      to alter electronic properties is demonstrated by low-temperature longitudinal
      Hall-effect measurements on a strained-silicon quantum well before and after
      release. Elastic strain sharing and film transfer offer an intriguing path
      towards complex, multiple-layer structures in which each layer's properties are
      controlled elastically, without the introduction of undesirable defects.

PMID- 16604082
TI  - The electrostatic character of the ribosomal surface enables extraordinarily
      rapid target location by ribotoxins.
AB  - Alpha-sarcin ribotoxins comprise a unique family of ribonucleases that cripple
      the ribosome by catalyzing endoribonucleolytic cleavage of ribosomal RNA at a
      specific location in the sarcin/ricin loop (SRL). The SRL structure alone is
      cleaved site-specifically by the ribotoxin, but the ribosomal context enhances
      the reaction rate by several orders of magnitude. We show that, for the alpha
      sarcin-like ribotoxin restrictocin, this catalytic advantage arises from
      favorable electrostatic interactions with the ribosome. Restrictocin binds at
      many sites on the ribosomal surface and under certain conditions cleaves the SRL
      with a second-order rate constant of 1.7 x 10(10) M(-1) s(-1), a value that
      matches the predicted frequency of random restrictocin-ribosome encounters. The
      results suggest a mechanism of target location whereby restrictocin encounters
      ribosomes randomly and diffuses within the ribosomal electrostatic field to the
      SRL. These studies show a role for electrostatics in protein-ribosome
      recognition.

PMID- 16604083
TI  - Nucleophosmin is selectively deposited on mRNA during polyadenylation.
AB  - Nucleophosmin (NPM), an abundant, predominantly nucleolar protein that influences
      numerous cellular processes, was shown to specifically associate with the bodies
      of messenger RNAs as a result of the process of 3'-end formation. NPM deposition
      requires polyadenylation but not the 3' cleavage event to occur on the
      transcript. Furthermore, the protein does not associate with RNAs bearing a
      preformed poly(A) tail or with mRNAs that have undergone cleavage but not
      polyadenylation. A region within 10 bases upstream of the AAUAAA element is
      required for NPM association, but deposition of the protein seems to be sequence
      independent. NPM association with poly(A)(+) mRNAs was also demonstrated in vivo.
      NPM, therefore, represents a mark left on transcripts as a result of 3'-end
      processing and may have a role in one or more of a variety of post
      transcriptional processes influenced by the polyadenylation event.

PMID- 16604084
TI  - A coproofreading Zn(2+)-dependent exonuclease within a bacterial replicase.
AB  - The proofreading exonucleases of all DNA replicases contain acidic residues that
      chelate two Mg(2+) ions that participate in catalysis. DNA polymerase III
      holoenzymes contain their proofreading activity in a separate subunit, epsilon,
      which binds the polymerase subunit, alpha, through alpha's N-terminal php domain.
      Here we demonstrate that the alpha php domain contains a novel Zn(2+)-dependent
      3' --> 5' exonuclease that preferentially removes mispaired nucleotides,
      providing the first example of a coediting nuclease.

PMID- 16604085
TI  - Experimental therapy of African trypanosomiasis with a nanobody-conjugated human
      trypanolytic factor.
AB  - High systemic drug toxicity and increasing prevalence of drug resistance hampers
      efficient treatment of human African trypanosomiasis (HAT). Hence, development of
      new highly specific trypanocidal drugs is necessary. Normal human serum (NHS)
      contains apolipoprotein L-I (apoL-I), which lyses African trypanosomes except
      resistant forms such as Trypanosoma brucei rhodesiense. T. b. rhodesiense
      expresses the apoL-I-neutralizing serum resistance-associated (SRA) protein,
      endowing this parasite with the ability to infect humans and cause HAT. A
      truncated apoL-I (Tr-apoL-I) has been engineered by deleting its SRA-interacting
      domain, which makes it lytic for T. b. rhodesiense. Here, we conjugated Tr-apoL-I
      with a single-domain antibody (nanobody) that efficiently targets conserved
      cryptic epitopes of the variant surface glycoprotein (VSG) of trypanosomes to
      generate a new manmade type of immunotoxin with potential for trypanosomiasis
      therapy. Treatment with this engineered conjugate resulted in clear curative and
      alleviating effects on acute and chronic infections of mice with both NHS
      resistant and NHS-sensitive trypanosomes.

PMID- 16604086
TI  - Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake.
AB  - Leptin controls food intake by regulating the transcription of key neuropeptides
      in the hypothalamus. The mechanism by which leptin regulates gene expression is
      unclear, however. Here we show that delivery of adenovirus encoding a
      constitutively nuclear mutant FoxO1, a transcription factor known to control
      liver metabolism and pancreatic beta-cell function, to the hypothalamic arcuate
      nucleus of rodents results in a loss of the ability of leptin to curtail food
      intake and suppress expression of Agrp. Conversely, a transactivation-deficient
      FoxO1 mutant prevents induction of Agrp by fasting. We also find that FoxO1 and
      the transcription factor Stat3 exert opposing actions on the expression of Agrp
      and Pomc through transcriptional squelching. FoxO1 promotes opposite patterns of
      coactivator-corepressor exchange at the Pomc and Agrp promoters, resulting in
      activation of Agrp and inhibition of Pomc. Thus, FoxO1 represents a shared
      component of pathways integrating food intake and peripheral metabolism.

PMID- 16604087
TI  - Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein
      transduction domain prevents allergic inflammation.
AB  - CTLA-4 is a negative regulator of T-cell activation, and its inhibitory effects
      can be accomplished either by competition with CD28 or by transmitting negative
      signals through its intracellular domain. To utilize the cytoplasmic domain of
      CTLA-4 to suppress allergic inflammation, we fused it to a novel protein
      transduction domain in the human transcriptional factor Hph-1. Transduction
      efficiency was verified in vitro and in vivo after ocular, intranasal and
      intradermal administration. After transduction into T cells, the Hph-1-ctCTLA-4
      fusion protein inhibited the production of interleukin (IL)-2, and downregulated
      CD69 and CD25. Intranasal administration of Hph-1-ctCTLA-4 resulted in markedly
      reduced infiltration of inflammatory cells, secretion of T helper type 2 (T(H)2)
      cytokines, serum IgE levels and airway hyper-responsiveness in a mouse model of
      allergic airway inflammation. These results indicated that Hph-1-ctCTLA-4
      constitutes an effective immunosuppressive protein drug for potential use in the
      treatment of allergic asthma, via nasal administration.

PMID- 16604088
TI  - CNTF reverses obesity-induced insulin resistance by activating skeletal muscle
      AMPK.
AB  - Ciliary neurotrophic factor (CNTF) induces weight loss and improves glucose
      tolerance in humans and rodents. CNTF is thought to act centrally by inducing
      hypothalamic neurogenesis to modulate food intake and peripherally by altering
      hepatic gene expression, in a manner similar to that of leptin. Here, we show
      that CNTF signals through the CNTFRalpha-IL-6R-gp130beta receptor complex to
      increase fatty-acid oxidation and reduce insulin resistance in skeletal muscle by
      activating AMP-activated protein kinase (AMPK), independent of signaling through
      the brain. Thus, our findings further show that the antiobesogenic effects of
      CNTF in the periphery result from direct effects on skeletal muscle, and that
      these peripheral effects are not suppressed by diet-induced or genetic models of
      obesity, an essential requirement for the therapeutic treatment of obesity
      related diseases.

PMID- 16604089
TI  - Hypothalamic huntingtin-associated protein 1 as a mediator of feeding behavior.
AB  - The hypothalamus responds to circulating leptin and insulin in the control of
      food intake and body weight. A number of neurotransmitters in the hypothalamus,
      including gamma-aminobutyric acid (GABA), also have key roles in feeding.
      Huntingtin-associated protein 1 (Hap1) is expressed more abundantly in the
      hypothalamus than in other brain regions, and lack of Hap1 in mice leads to early
      postnatal death. Hap1 is also involved in intracellular trafficking of the
      GABA(A) receptor. Here, we report that fasting upregulates the expression of Hap1
      in the rodent hypothalamus, whereas intracerebroventricular administration of
      insulin downregulates Hap1 by increasing its degradation through ubiquitination.
      Decreasing the expression of mouse hypothalamic Hap1 by siRNA reduces the level
      and activity of hypothalamic GABA(A) receptors and causes a decrease in food
      intake and body weight. These findings provide evidence linking hypothalamic Hap1
      to GABA in the stimulation of feeding and suggest that this mechanism is involved
      in the feeding-inhibitory actions of insulin in the brain.

PMID- 16604090
TI  - Inhibition of TRPM2 cation channels by N-(p-amylcinnamoyl)anthranilic acid.
AB  - 1. TRPM2 is a Ca2+ -permeable nonselective cation channel activated by
      intracellular ADP-ribose (ADPR) and by hydrogen peroxide (H2O2). We investigated
      the modulation of TRPM2 activity by N-(p-amylcinnamoyl)anthranilic acid (ACA).
      ACA has previously been reported to inhibit phospholipase A2 (PLA2). 2. Using
      patch-clamp and calcium-imaging techniques, we show that extracellular
      application of 20 microM ACA completely blocked ADPR-induced whole-cell currents
      and H2O2-induced Ca2+ signals (IC50 = 1.7 microM) in HEK293 cells transfected
      with human TRPM2. Two other PLA2 inhibitors, p-bromophenacyl bromide (BPB; 100
      microM) and arachidonyl trifluoromethyl ketone (20 microM), had no significant
      effect on ADPR-stimulated TRPM2 activity. 3. Inhibition of TRPM2 whole-cell
      currents by ACA was voltage independent and accelerated at decreased pH. ACA was
      ineffective when applied intracellularly. The single-channel conductance was not
      changed during ACA treatment, suggesting a reduction of TRPM2 open probability by
      modulating channel gating. 4. ACA (20 microM) also blocked currents through human
      TRPM8 and TRPC6 expressed in HEK293 cells, while BPB (100 microM) was
      ineffective. TRPC6-mediated currents (IC50 = 2.3 microM) and TRPM8-induced Ca2+
      signals (IC50 = 3.9 microM) were blocked in a concentration-dependent manner. 5.
      ADPR-induced currents in human U937 cells, endogeneously expressing TRPM2
      protein, were fully suppressed by 20 microM ACA. 6. Our data indicate that ACA
      modulates the activity of different TRP channels independent of PLA2 inhibition.
      Owing to its high potency and efficacy ACA can serve, in combination with other
      blockers, as a useful tool for studying the unknown function of TRPM2 in native
      cells.

PMID- 16604091
TI  - How corticosteroids control inflammation: Quintiles Prize Lecture 2005.
AB  - Corticosteroids are the most effective anti-inflammatory therapy for many chronic
      inflammatory diseases, such as asthma but are relatively ineffective in other
      diseases such as chronic obstructive pulmonary disease (COPD). Chronic
      inflammation is characterised by the increased expression of multiple
      inflammatory genes that are regulated by proinflammatory transcription factors,
      such as nuclear factor-kappaB and activator protein-1, that bind to and activate
      coactivator molecules, which then acetylate core histones to switch on gene
      transcription. Corticosteroids suppress the multiple inflammatory genes that are
      activated in chronic inflammatory diseases, such as asthma, mainly by reversing
      histone acetylation of activated inflammatory genes through binding of liganded
      glucocorticoid receptors (GR) to coactivators and recruitment of histone
      deacetylase-2 (HDAC2) to the activated transcription complex. At higher
      concentrations of corticosteroids GR homodimers also interact with DNA
      recognition sites to active transcription of anti-inflammatory genes and to
      inhibit transcription of several genes linked to corticosteroid side effects. In
      patients with COPD and severe asthma and in asthmatic patients who smoke HDAC2 is
      markedly reduced in activity and expression as a result of oxidative/nitrative
      stress so that inflammation becomes resistant to the anti-inflammatory actions of
      corticosteroids. Theophylline, by activating HDAC, may reverse this
      corticosteroid resistance. This research may lead to the development of novel
      anti-inflammatory approaches to manage severe inflammatory diseases.

PMID- 16604092
TI  - Rosmarinic acid as a downstream inhibitor of IKK-beta in TNF-alpha-induced
      upregulation of CCL11 and CCR3.
AB  - 1. Tumor necrosis factor (TNF)-alpha is known to induce the expression of CCL11
      and CCR3 via the activation of NF-kappaB. CCL11 (eotaxin), the C-C chemokine, is
      a potent chemoattractant for eosinophils and Th2 lymphocytes, and CCR3 is the
      receptor for CCL11. 2. In order to determine the effects of rosmarinic acid on
      the TNF-alpha-induced upregulation of CCL11 and CCR3 in human dermal fibroblasts,
      we performed an enzyme-linked immunosorbent assay for CCL11 and a Western blot
      assay for CCR3. The TNF-alpha-induced expression of CCL11 and CCR3 genes was
      attenuated by rosmarinic acid. 3. In our NF-kappaB luciferase reporter system,
      TNF-alpha-induced NF-kappaB activation was observed to be reduced by rosmarinic
      acid. In accordance with this result, rosmarinic acid also inhibited TNF-alpha
      induced phosphorylation and degradation of IkappaB-alpha, as well as nuclear
      translocation of NF-kappaB heterodimer induced by TNF-alpha. This suggests that
      rosmarinic acid downregulates the expression of CCL11 and CCR3 via the inhibition
      of NF-kappaB activation signaling. 4. Using the NF-kappaB luciferase reporter
      system, Western blot analysis, and IKK-beta activity assay, we determined that
      rosmarinic acid inhibits IKK-beta activity in NF-kappaB signaling, which
      upregulates the expression of CCL11 and CCR3. Additionally, TNF-alpha-induced
      secretion of soluble intercellular adhesion molecule-1 and soluble vascular cell
      adhesion molecule-1 molecules was found to be attenuated by rosmarinic acid. 5.
      Our results show that rosmarinic acid inhibits the expression of CCL11 and CCR3
      by suppressing the IKK-beta activity in NF-kappaB activation signaling. Further,
      these results suggest that rosmarinic acid might inhibit the expression of NF
      kappaB promoter-related genes.

PMID- 16604094
TI  - Cataract in older women exposed to hormone replacement.

PMID- 16604093
TI  - GW627368X ((N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2
      yl)phenyl]acetyl} benzene sulphonamide): a novel, potent and selective prostanoid
      EP4 receptor antagonist.
AB  - 1. N-{2-[4-(4,9-diethoxy-1-oxo-1,3-dihydro-2H-benzo[f]isoindol-2
      yl)phenyl]acetyl}benzene sulphonamide (GW627368X) is a novel, potent and
      selective competitive antagonist of prostanoid EP4 receptors with additional
      human TP receptor affinity. 2. At recombinant human prostanoid EP4 receptors
      expressed in HEK293 cells, GW627368X produced parallel rightward shifts of PGE2
      concentration-effect (E/[A]) curves resulting in an affinity (pKb) estimate of
      7.9 +/- 0.4 and a Schild slpoe not significantly different from unity. The
      affinity was independent of the agonist used. 4. In rings of phenylephrine
      precontracted piglet saphenous vein, GW627368X (30-300 nM) produced parallel
      rightward displacement of PGE2 E/[A] curves (pKb = 9.2 +/- 0.2; slope = 1). 4.
      GW627368X appears to bind to human prostanoid TP receptors but not the TP
      receptors of other species. In human washed platelets, GW627368X (10 microM)
      produced 100% inhibition of U-46619 (EC100)-induced aggregation (approximate pA2
      approximately 7.0). However, in rings of rabbit and piglet saphenous vein and of
      guinea-pig aorta GW627368X (10 microM) did not displace U-46619 E/[A] curves
      indicating an affinity of < 5.0 for rabbit and guinea-pig prostanoid TP
      receptors. 5. In functional assays GW627368X is devoid of both agonism and
      antagonist affinity for prostanoid CRTH2, EP2, EP3, IP and FP receptors. At
      prostanoid EP1 receptors, GW627368X was an antagonist with a pA2 of 6.0, and at
      prostanoid IP receptors the compound increased the maximum effect of iloprost by
      55%. At rabbit prostanoid EP2 receptors the pA2 of GW627368X was < 5.0. 6. In
      competition radioligand bioassays, GW627368X had affinity for human prostanoid
      EP4 and TP receptors (pKi = 7.0 +/- 0.2 (n = 10) and 6.8 (n = 2), respectively).
      Affinity for all other human prostanoid receptors was < 5.3. 7. GW627368X will be
      a valuable tool to explore the role of the prostanoid EP4 receptor in many
      physiological and pathological settings.

PMID- 16604096
TI  - Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic
      myelomonocytic leukemia.
AB  - Prognosis in chronic myelomonocytic leukemia (CMML) is unfavorable and the
      optimal therapy remains uncertain. Currently, allogeneic stem cell
      transplantation is the only known curative therapeutic option. However, the data
      available are limited and restricted to small retrospective series. There is even
      less information on the use of donor lymphocyte infusions (DLI) for this disease.
      We reviewed our experience of allogeneic stem cell transplantation and DLI for
      adults with CMML. Seventeen consecutive adults underwent allogeneic stem cell
      transplantation from related (n=14) or unrelated (n=3) donors. Median age was 50
      years (range 26-60). Seven patients (41%) demonstrated relapse or persistent
      disease at a median of 6 months (range 3-55.5). Five patients underwent DLI for
      morphologic relapse and one for mixed donor chimerism. Two patients achieved
      durable complete remissions of 15 months each. The overall transplant-related
      mortality was 41% (n=7). With a median follow-up of 34.5 months, three patients
      (18%) currently remain alive and in continuous CR. The current study demonstrates
      a graft-versus-leukemia effect in CMML, both for allogeneic stem cell
      transplantation and for DLI. Nevertheless, consistent with reported experience of
      others, overall outcomes remain less than optimal and unpredictable.

PMID- 16604097
TI  - Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA
      cannot be detected in the healthy seropositive individual.
AB  - Allogeneic stem cell transplantation is often complicated by reactivation of
      herpesviruses. Mesenchymal stem cells (MSC) are immunomodulatory and may be used
      to treat graft-versus-host disease. We investigated if herpesviruses infect and
      can be transmitted by MSC, and if MSC suppress immune responses to various
      infectious agents. Mesenchymal stem cells from healthy seropositive donors were
      evaluated with polymerase chain reaction for the most common herpesviruses:
      cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), herpes simplex virus
      type 2, Epstein-Barr virus (EBV) and varicella zoster virus. The cytopathological
      effect (CPE) was investigated and viral antigens analyzed by immunofluorescence
      after in vitro exposure to CMV, HSV-1 and EBV. We also studied MSC effect on
      lymphocyte stimulation induced by various infectious agents. No viral DNA could
      be detected in MSC isolated from healthy seropositive individuals. However, a CPE
      was noted and intracellular viral antigens detected after infection in vitro by
      CMV and HSV-1, but not by EBV. The CMV and HSV-1 infections were productive.
      Lymphocyte proliferation by herpesviruses, candida mannan and protein A from
      Staphylococcus aureus was suppressed by MSC. The data indicate that the risk of
      herpesvirus transmission by transplantation of MSC from healthy seropositive
      donors is low. However, MSC may be susceptible to infection if infused in a
      patient with CMV or HSV-1 viremia. MSC transplantation may compromise the host's
      defense against infectious agents.

PMID- 16604098
TI  - Prevalence of conception and pregnancy outcomes after hematopoietic cell
      transplantation: report from the Bone Marrow Transplant Survivor Study.
AB  - We conducted a retrospective study to describe the magnitude of compromise in
      reproductive function and investigate pregnancy outcomes in 619 women and
      partners of men treated with autologous (n=241) or allogeneic (n=378)
      hematopoietic cell transplantation (HCT) between 21 and 45 years of age, and
      surviving 2 or more years. Median age at HCT was 33.3 years and median time since
      HCT 7.7 years. Mailed questionnaires captured pregnancies and their outcomes
      (live birth, stillbirth, miscarriage). Thirty-four patients reported 54
      pregnancies after HCT (26 males, 40 pregnancies; eight females, 14 pregnancies),
      of which 46 resulted in live births. Factors associated with reporting no
      conception included older age at HCT (> or =30 years: odds ratio (OR)=4.8),
      female sex (OR=3.0), and total body irradiation (OR=3.3). Prevalence of
      conception and pregnancy outcomes in HCT survivors were compared to those of 301
      nearest-age siblings. Although the risk for not reporting a conception was
      significantly increased among HCT survivors (OR=36), survivors were not
      significantly more likely than siblings to report miscarriage or stillbirth
      (OR=0.7). Although prevalence of conception is diminished after HCT, if pregnancy
      does occur, outcome is likely to be favorable. Patients should be counseled prior
      to transplant regarding strategies to preserve fertility.

PMID- 16604099
TI  - Rx-to-OTC switches: trends and factors underlying success.
AB  - The US Food and Drug Administration defines an Rx-to-OTC switch as over-the
      counter (OTC) marketing of a drug product that was once a prescription (Rx) drug
      for the same indication, with the same strength, dose, duration of use, dosage
      form, population and route of administration. Here, we examine the rationale
      behind switches, the process of switches and historical case studies of switches
      in the United States to understand the factors for success and expected future
      trends.

PMID- 16604100
TI  - A role for fMRI in optimizing CNS drug development.
AB  - Drug development today needs to balance agility, speed and risk in defining the
      probability of success for molecules, mechanisms and therapeutic concepts. New
      techniques in functional magnetic resonance imaging (fMRI) promise to be part of
      a sequence that could transform drug development for disorders of the central
      nervous system (CNS) by examining brain systems and their functional activation
      dynamically. The brain is complex and multiple transmitters and intersecting
      brain circuits are implicated in many CNS disorders. CNS therapeutics are
      designed against specific CNS targets, many of which are unprecedented. The
      challenge is to reveal the functional consequences of these interactions to
      assess therapeutic potential. fMRI can help optimize CNS drug discovery by
      providing a key metric that can increase confidence in early decision-making,
      thereby improving success rates and reducing risk, development times and costs of
      drug development.

PMID- 16604101
TI  - Clonal and non-clonal chromosome aberrations and genome variation and aberration.
AB  - The theoretical view that genome aberrations rather than gene mutations cause a
      majority of cancers has gained increasing support from recent experimental data.
      Genetic aberration at the chromosome level is a key aspect of genome aberration
      and the systematic definition of chromosomal aberrations with their impact on
      genome variation and cancer genome evolution is of great importance. However,
      traditionally, efforts have focused on recurrent clonal chromosome aberrations
      (CCAs). The significance of stochastic non-clonal chromosome aberrations (NCCAs)
      is discussed in this paper with emphasis on the simple types of NCCAs that have
      until recently been considered "non-significant background". Comparison of
      various subtypes of transitional and late-stage CCAs with simple and complex
      types of NCCAs has uncovered a dynamic relationship among NCCAs, CCAs, overall
      genomic instability, and karyotypic evolution, as well as the stochastic nature
      of cancer evolution. Here, we review concepts and methodologies to measure NCCAs
      and discuss the possible causative mechanism and consequences of NCCAs. This
      study raises challenging questions regarding the concept of cancer evolution
      driven by stochastic chromosomal aberration mediated genome irregularities that
      could have repercussions reaching far beyond cancer and organismal genomes.

PMID- 16604102
TI  - Zebrafish: chiasmata and interference.
AB  - With immunofluorescence microscopy, the positions of centromeres and MLH1 (MutL
      homolog) foci representing the sites of presumptive chiasmata are shown for
      zebrafish (Danio rerio Hamilton 1822) synaptonemal complexes (SCs) in
      spermatocyte nuclei at meiotic prophase. Most SCs have a single focus and a few
      (7 of 140) have 2 chiasmata. MLH1 foci tend to be in the distal regions of SCs,
      with progressively fewer occurring towards the middle of the SCs. This non-random
      distribution suggests chiasma interference. Synaptic initiation, as well as
      replication protein A (RPA) foci at the chromosome ends, correlates with the
      distal localization of MLH1 foci. These observations may provide the physical
      basis for the reported limited genetic recombination in the centromeric region of
      androgenetic offspring of a male.

PMID- 16604103
TI  - Molecular structure and organization of the wheat genomic manganese superoxide
      dismutase gene.
AB  - The genomic structure of a manganese superoxide dismutase (MnSOD) gene in wheat
      was elucidated by sequencing a clone from a BAC library of a stripe rust
      resistant wheat line. The clone was identified by hybridization with a wheat
      MnSOD cDNA. The gene consisted of 6 exons interrupted by 5 introns with a total
      length of 4770 nucleotides from the start codon to the termination codon. The
      wheat MnSOD gene was the longest among those sequenced from plant species. The
      transcription initiation site was preceded by a G+C-rich promoter without a TATA
      or CAAT box. The promoter contained many putative cis-acting regulatory elements,
      including an abscisic acid (ABA)-responsive element, a stress-responsive element,
      and a GC-repeat, as well as several other structural features in common with the
      promoter of the rice MnSOD gene. A Stowaway-like transposable element was found
      in intron 5 of the wheat MnSOD gene, but further investigation revealed the
      transposable element was not present in all copies of the MnSOD genes.

PMID- 16604104
TI  - Molecular phylogeny of Cucumis species as revealed by consensus chloroplast SSR
      marker length and sequence variation.
AB  - To investigate phylogenetic relationships in the genus Cucumis, 9 consensus
      chloroplast simple sequence repeat (ccSSR) primer pairs (ccSSR3, 9, 11, 13, 14,
      17, 20, 21, and 23) were employed for DNA fragment length variation and 5
      amplified fragments, ccSSR4, 12, 13, 19, and 20, were sequenced using total DNA
      from 13 accessions representing 7 African Cucumis species (x = 12), 3 Cucumis
      melo L. (x = 12) accessions, 2 Cucumis sativus L. (x = 7) accessions, and 1
      Cucumis hystrix Chakr. (x = 12) accession. A Citrullus lanatus (Thunb.) Matsum. &
      Nakai (x = 11) accession was used as an outgroup. While fragment length analysis
      revealed the existence of 3 major species clusters (i.e., a group of African
      Cucumis species, a group composed of C. melo accessions, and a group containing
      C. sativus and C. hystrix species), sequence variation analysis identified 2
      major species clusters (i.e., a group of African Cucumis species and a group
      composed of C. melo, C. sativus, and C. hystrix species). Comparative analysis
      using nuclear DNA (previous studies) and cpDNA sequence substitution data
      resulted in the placement of C. melo and C. sativus in different cluster
      groupings. Thus, both nuclear and cytoplasmic DNA should be employed and compared
      when a putative progenitor or specimens of an ancestral Cucumis species lineage
      is investigated. In addition, C. ficifolius (2x) and C. aculeatus (4x) of the
      African Cucumis species clustered together in this study. This result does not
      agree with reported isozyme analyses, but does agree with previously
      characterized chromosome homologies between these 2 species. Although African
      Cucumis species and C. hystrix do not share a close relationship, genetic
      affinities between C. sativus and C. hystrix are considerable. Combined evidence
      from previously published studies and data presented herein lend support to the
      hypothesis that C. hystrix is either a progenitor species of C. sativus or that
      they at least share a common ancestral lineage.

PMID- 16604105
TI  - New evidence from Sinapis alba L. for ancestral triplication in a crucifer
      genome.
AB  - We present clear evidence of ancestral genome triplication in Sinapis alba, a
      close relative of the cultivated Brassica species. Exceptionally high levels of
      heterozygosity in the parents of an F1 intercross permitted the mapping of an
      estimated 87% of all detected restriction fragment length polymorphism (RFLP)
      loci, with each RFLP probe typically detecting 2 or 3 loci. These duplicated loci
      were arranged in 8 triplicated homologous linkage blocks and 2 small, duplicated,
      homologous linkage blocks covering the majority of the S. alba genome. Several
      large-scale inversions and translocations appear to have rearranged the order of
      loci within homologous blocks. The role of successive polyploidization events on
      the evolution of crucifer species is discussed.

PMID- 16604106
TI  - Cloning and sequence analysis of 2 different acetylcholinesterase genes in
      Rhopalosiphum padi and Sitobion avenae.
AB  - Two genes encoding different acetylcholinesterases (AChE) were successfully
      cloned from 2 species of aphid, Rhopalosiphum padi (L.) and Sitobion avenae (F.).
      They were named Rp.AChE1 (GenBank accession No. AY707318), Rp.AChE2 (AY667435),
      Sa.AChE1 (AY707319), and Sa.AChE2 (AY819704), and were 2133, 2363, 2131, and 2362
      bp in length and encoded 664, 676, 664, and 676 amino acids, respectively. All of
      them shared the characteristics of the AChE family: catalytic tiads, 3 intra
      chain disulfide bridges, an acyl pocket, and the conservative aromatic residues
      for the active site of the gorge. Sequence analysis revealed that Rp.AChE1 and
      Sa.AChE1 showed higher identity to the reported orthologous genes of Drosophila
      AChE, and Rp.AChE2 and Sa.AChE2 to paralogous genes. However, in each of the
      aphids, the 2 genes from the same species shared only 29% identity between one
      another. It was therefore concluded that each of the aphids has 2 different AChE
      genes, which are either orthologous or paralogous to Drosophila AChE. The high
      conservation of AChE1 and AChE2 indicated that 2 acetylcholinesterases exist
      popularly and that both might function in aphids.

PMID- 16604107
TI  - Genome size variation in the Artemisia arborescens complex (Asteraceae,
      Anthemideae) and its cultivars.
AB  - Different wild Mediterranean populations of Artemisia arborescens from diverse
      locations representing its geographical distribution, as well as some of its well
      known cultivars and some specimens cultivated as ornamentals in gardens, streets,
      roads and nurseries, were analysed for genome size. Other closely related species
      endemic to Macaronesia, Artemisia canariensis, Artemisia argentea, and Artemisia
      gorgonum, were also analysed, and their nuclear DNA amount has been related to
      the biogeography of this group of species. Additionally, 5 populations of the
      closely related Artemisia absinthium were analysed to establish comparisons.
      Measurements acquired by flow cytometry ranged from 8.29 to 11.61 pg for 2C
      values. Statistically significant differences of 2C nuclear DNA amounts with
      respect to factors such as insularity or domestication have been detected.
      However, quite a low intraspecific genome size variation has been found in these
      species. Furthermore, the study also addressed the possible hybrid origins and
      possible misidentifications of some of the supposed cultivars of A. arborescens.

PMID- 16604108
TI  - Phylogeny of the sex-determining gene Sex-lethal in insects.
AB  - The Sex-lethal (SXL) protein belongs to the family of RNA-binding proteins and is
      involved in the regulation of pre-mRNA splicing. SXL has undergone an obvious
      change of function during the evolution of the insect clade. The gene has
      acquired a pivotal role in the sex-determining pathway of Drosophila, although it
      does not act as a sex determiner in non-drosophilids. We collected SXL sequences
      of insect species ranging from the pea aphid (Acyrtho siphom pisum) to Drosophila
      melanogaster by searching published articles, sequencing cDNAs, and exploiting
      homology searches in public EST and whole-genome databases. The SXL protein has
      moderately conserved N- and C-terminal regions and a well-conserved central
      region including 2 RNA recognition motifs. Our phylogenetic analysis shows that a
      single orthologue of the Drosophila Sex-lethal (Sxl) gene is present in the
      genomes of the malaria mosquito Anopheles gambiae, the honeybee Apis mellifera,
      the silkworm Bombyx mori, and the red flour beetle Tribolium castaneum. The D.
      melanogaster, D. erecta, and D. pseudoobscura genomes, however, contain 2
      paralogous genes, Sxl and CG3056, which are orthologous to the Anopheles, Apis,
      Bombyx, and Tribolium Sxl. Hence, a duplication in the fly clade generated Sxl
      and CG3056. Our hypothesis maintains that one of the genes, Sxl, adopted the new
      function of sex determiner in Drosophila, whereas the other, CG3056, continued to
      serve some or all of the yet-unknown ancestral functions.

PMID- 16604109
TI  - Molecular cloning and chromosomal localization of the Bombyx Sex-lethal gene.
AB  - We cloned Bm-Sxl, an orthologue of the Drosophila melanogaster Sex-lethal (Sxl)
      gene from embryos of Bombyx mori. The full-length cDNAs were of 2 sizes, 1528 and
      1339 bp, and were named Bm-Sxl-L and Bm-Sxl-S, respectively. Bm-Sxl-L consists of
      8 exons and spans more than 20 kb of genomic DNA. The open reading frame (ORF)
      codes for a protein 336 amino acids in length. Bm-Sxl-S is a splice variant that
      lacks the second exon. This creates a new translation start 138 nucleotides
      downstream and an ORF that codes for 46 amino acids fewer at the N-terminus.
      Linkage analysis using an F2 panel mapped Bm-Sxl to linkage group 16 at 69.8 cM.
      We isolated 2 BACs that include the Bm-Sxl gene. With BAC-FISH we located Bm-Sxl
      cytogenetically on the chromosome corresponding to linkage group 16 (LG16) at
      position >68.8 cM.

PMID- 16604110
TI  - Chromosome elimination in germ line-soma differentiation of Acricotopus lucidus
      (Diptera, Chironomidae).
AB  - During germ line-soma differentiation in early syncytial embryonic development of
      the chironomid Acricotopus lucidus, a complement of supernumerary chromosomes,
      the so-called germ line limited chromosomes (Ks), is excluded from the future
      somatic nuclei in the course of elimination mitoses. The Ks lag behind in the
      equatorial plane, while the somatic chromosomes (Ss) segregate equally. After
      elimination mitoses, the Ks are only present in the pole cells, the primary germ
      cells. In the divisions before their elimination, the Ks frequently showed
      delayed separation of sister chromatids with high-frequency formation of
      anaphasic bridges and lagging in pole movement as detected in 4',6-diamidino-2
      phenylindole (DAPI)-stained squash preparations of early embryos. To determine if
      all of the Ks are eliminated in one step during a single mitosis, a fluorescence
      in situ hybridization (FISH) analysis of early embryonic divisions was performed
      using probes of germ line specific repetitive DNA sequences, which specifically
      label the Ks in their centromeric regions. In most cases, all of the Ks are lost
      in one mitosis; however, occasionally one or several of the Ks can escape their
      elimination by segregating and moving poleward together with the Ss. The escaping
      Ks will then be eliminated in one of the following mitoses. This clearly
      indicates that the specific conditions to eliminate Ks are not restricted to only
      one division. Possible mechanisms of elimination of Ks are discussed.

PMID- 16604111
TI  - Rapid evolution in sequence and length of the nuclear-located gene for
      mitochondrial L2 ribosomal protein in cereals.
AB  - The L2 ribosomal protein is typically one of the most conserved proteins in the
      ribosome and is universally present in bacterial, archaeal, and eukaryotic
      cytosolic and organellar ribosomes. It is usually 260-270 amino acids long and
      its binding to the large-subunit ribosomal RNA near the peptidyl transferase
      center is mediated by a beta-barrel RNA-binding domain with 10 beta strands. In
      the diverse land plants Marchantia polymorpha (liverwort) and Oryza sativa
      (rice), the mitochondrial-encoded L2 ribosomal protein is about 500 amino acids
      long owing to a centrally located expansion containing the beta3-beta4 strand
      region. We have determined that, in wheat, the functional rpl2 gene has been
      transferred to the nucleus and much of the plant-specific internal insert has
      been deleted. Its mRNA is only 1.2 kb, and two expressed copies in wheat encode
      proteins of 318 and 319 amino acids, so they are considerably shorter than the
      maize nuclear-located rpl2 gene of 448 codons. Comparative sequence analysis of
      cereal mitochondrial L2 ribosomal proteins indicates that the mid region has
      undergone unexpectedly rapid evolution during the last 60 million years.

PMID- 16604112
TI  - Generation of SNP markers for short straw in oat (Avena sativa L.).
AB  - Short straw is a desired trait in oat germplasm (Avena sativa L.). Marker
      assisted selection, a key tool for achieving this objective, is limited by the
      presence and number of available markers. Here, we have attempted to develop
      markers sufficiently linked to a gene specifying short straw so that marker
      assisted selection could be applied. Bulked-segregant analysis was used to
      identify anonymous PCR-based markers associated with the dwarfing gene Dw6 in an
      F2 population from the cross between A. sativa "Aslak" and A. sativa "Kontant".
      One random amplified polymorphic DNA (RAPD) and 1 retrotransposon-microsatellite
      amplified polymorphism (REMAP) marker were found to be associated with height.
      These were converted into codominant single-nucleotide polymorphism (SNP)
      markers. The SNP-REMAP and the SNP-RAPD markers were located 5.2 and 12.6 cM from
      Dw6, respectively. They can be used in future efforts both to enhance oat
      germplasm by application of molecular markers and to determine the nature of the
      gene through positional cloning.

PMID- 16604113
TI  - [Modern bacterial taxonomy: techniques review--application to bacteria that
      nodulate leguminous plants (BNL)].
AB  - Taxonomy is the science that studies the relationships between organisms. It
      comprises classification, nomenclature, and identification. Modern bacterial
      taxonomy is polyphasic. This means that it is based on several molecular
      techniques, each one retrieving the information at different cellular levels
      (proteins, fatty acids, DNA...). The obtained results are combined and analysed
      to reach a "consensus taxonomy" of a microorganism. Until 1970, a small number of
      classification techniques were available for microbiologists (mainly phenotypic
      characterization was performed: a legume species nodulation ability for a
      Rhizobium, for example). With the development of techniques based on polymerase
      chain reaction for characterization, the bacterial taxonomy has undergone great
      changes. In particular, the classification of the legume nodulating bacteria has
      been repeatedly modified over the last 20 years. We present here a review of the
      currently used molecular techniques in bacterial characterization, with examples
      of application of these techniques for the study of the legume nodulating
      bacteria.

PMID- 16604114
TI  - Actinobacillus actinomycetemcomitans serotype-specific genotypes and periodontal
      status in Brazilian subjects.
AB  - Periodontitis is associated with members of the oral microbiota, such as
      Actinobacillus actinomycetemcomitans. To our knowledge, this is the first study
      to evaluate, by PCR, the occurrence of the six known bacterium serotypes that
      included subjects with and without periodontitis. Our group comprised 49
      Brazilian subjects. We studied 146 bacterial isolates from 23 patients with
      aggressive or chronic periodontitis and 26 subgingival specimens from subjects
      with or without periodontitis, all originating in our collection. Serotypes b and
      c were observed in similar frequencies, and no subject harboured d, e, or f
      serotype strains. Around 78% subjects had single-serotype infection. Mixed
      infection was seen only in aggressive periodontitis patients. An association
      between serotype b and healthy periodontium and between serotype c and chronic
      periodontitis was observed. Our results diverge from those previously reported,
      which may be explained by specific distribution patterns in distinct populations.
      The association of different serotypes with the same periodontal status or
      conversely of a serotype with different periodontal conditions indicates that
      organism serotyping should not be used as a sole reliable marker for predicting
      the outcome of the infection. Evaluation of factors involved in human oral cavity
      colonization by subsets of A. actinomycetemcomitans is essential for elucidating
      organism-host-environment relationships.

PMID- 16604115
TI  - Bioreactor studies on the endophytic fungus Entrophospora infrequens for the
      production of an anticancer alkaloid camptothecin.
AB  - Twigs (young and old) from Nothapodytes foetida growing in the Jammu and
      Mahabaleshwar regions in India were used for the isolation of 52 strains of
      endophytic fungi and were tested for their ability to produce the anticancer
      alkaloid camptothecin. One of the isolates from the inner bark tissue of the N.
      foetida plant growing in the Jammu region of J&K state, India, was found to
      produce detectable quantities of camptothecin and its derivatives when grown in a
      semi-synthetic liquid medium. Camptothecin was identified by physicochemical
      analysis and further confirmed by spectroscopic studies. No camptothecin was
      detected in zero time cultures or in uninoculated culture broth. The maximum
      yield of camptothecin was 0.575 +/- 0.031 mg/100 g of dry cell mass in 96 h in
      shake flasks, whereas 4.96 +/- 0.73 mg/100 g of dry mass was recorded in 48 h in
      a bioreactor.

PMID- 16604116
TI  - Biochemical and taxonomic characterization of bacteria associated with the
      crucifer root maggot (Delia radicum).
AB  - The crucifer root maggot, Delia radicum, is an important pest of cruciferous
      crops; however, little is known about its digestive biochemistry or resident gut
      microbiota. A culturing approach was used to survey the types of micro organisms
      associated with eggs, midgut, and faeces of larvae feeding on rutabaga. All
      bacteria isolated from the midgut and faecal materials were Gram-negative
      bacilli. Nine types of culturable bacteria were identified within the midgut
      based on analysis of 60 kDa chaperonin sequences and were generally gamma
      Proteobacteria, primarily Enterobacteriaceae. Carbohydrate utilization patterns,
      select biochemical pathways, and hydrolytic enzymes were examined using the
      API(R) system for each of the nine groups, revealing an exceptionally broad
      metabolic and hydrolytic potential. These studies suggest that resident
      alimentary tract microorganisms have the potential to contribute to host
      nutrition directly as a food source as well as by providing increased digestive
      potential.

PMID- 16604117
TI  - Identification of sulfoquinovosyl diacylglycerol as a major polar lipid in
      Marinococcus halophilus and Salinicoccus hispanicus and substitution with
      phosphatidylglycerol.
AB  - The sulfonolipid sulfoquinovosyl diacylglycerol normally associated with
      photosynthetic membranes was identified as a major lipid in Marinococcus
      halophilus, Salinicoccus hispanicus ("Marinococcus hispanicus"), and Marinococcus
      sp. H8 (Planococcus sp. H8). Phosphatidylglycerol and 0%-10% cardiolipin
      accounted for the remaining polar lipids in these moderately halophilic, Gram
      positive bacteria. Negative-ion fast atom bombardment mass spectrometry was used
      to quantify these three polar lipids from cells grown in media containing 0.03 to
      4 mol NaCl/L. All strains revealed dramatic shifts in the ratio of sulfonolipid
      to phospholipid dependent on the salinity of the growth media, when grown in
      media with low phosphate content. Highest sulfonolipid content occurred during
      best growth in 0.5-2 mol NaCl/L, approaching 80%-90% of the total polar lipids.
      It was demonstrated that growth of M. halophilus in the presence of elevated
      phosphate and low sulfate blocked the shift to decreased phospholipids most
      notably during growth in 0.5-2 mol NaCl/L, without significant influence on
      growth. The data suggest that in low-phosphate media the influence of NaCl
      concentration on growth rate (and resulting demand for phosphate by competing
      pathways) is the primary factor responsible for exchange between phospholipid and
      sulfonolipid. We conclude that sulfoquinovosyl diacylglycerol, by substitution
      with phospholipids, contributes to the ability of these Gram-positive cocci to
      adapt to changing ionic environments. A comparison of 16S rRNA established a
      close similarity between Planococcus sp. H8 and M. halophilus.

PMID- 16604118
TI  - Heterologous expression of two trichothecene P450 genes in Fusarium
      verticillioides.
AB  - Fusarium graminearum Z-3639 and F. sporotrichioides NRRL3299 produce the
      trichothecene mycotoxins 15-acetyldeoxynivalenol and T-2 toxin, respectively.
      These toxins differ in oxygenation at C-4, C-7, and C-8. In F. sporotrichioides,
      Tri1 (FsTri1) controls C-8 hydroxylation. To determine the function of an
      apparent F. graminearum Tri1 (FgTri1) homolog, both FsTri1 and FgTri1 genes were
      heterologously expressed in the trichothecene-nonproducing species F.
      verticillioides by fusing the Tri1 coding regions to the promoter of the
      fumonisin biosynthetic gene FUM8. FsTri1 and FgTri1 have been partially
      characterized by disruption analysis, and the results from these analyses suggest
      that FsTri1 most likely has a single function but that FgTri1 may have two
      functions. Transgenic F. verticillioides carrying the FsTri1 (FvF8FsTri1)
      converted exogenous isotrichodermin and calonectrin to 8-hydroxyisotrichodermin
      and 8-hydroxycalonectrin, respectively. Transgenic F. verticillioides carrying
      FgTri1 (FvF8FgTri1) converted isotrichodermin to a mixture of 7
      hydroxyisotrichodermin and 8-hydroxyisotrichodermin but converted calonectrin to
      a mixture of 7-hydroxycalonectrin, 8-hydroxycalonectrin, and 3,15
      diacetyldeoxynivalenol. A fourth compound, 7,8-dihydroxycalonectrin, was
      identified in large-scale F. verticillioides FvF8FgTri1 cultures fed
      isotrichodermin. Our results indicate that FgTri1 controls both C-7 and C-8
      hydroxylation but that FsTri1 controls only C-8 hydroxylation. Our studies also
      demonstrate that F. verticillioides can metabolize some trichothecenes by adding
      an acetyl group to C-3 or by removing acetyl groups from C-4 or C-15. In
      addition, wild-type F. verticillioides can convert 7,8-dihydroxycalonectrin to
      3,15-diacetyldeoxynivalenol.

PMID- 16604119
TI  - Effect of organic N source on bacterial growth, lipo-chitooligosaccharide
      production, and early soybean nodulation by Bradyrhizobium japonicum.
AB  - Production of Bradyrhizobium japonicum inoculants is problematic because high
      inoculation rates are necessary but expensive, while production of rhizobial Nod
      factors (lipo-chitooligosaccharides (LCOs)), key signal molecules in the
      establishment of legume-rhizobia symbioses, may be inhibited at high culture cell
      densities. We conducted experiments to determine the effects of growth medium N
      source on B. japonicum growth, LCO production, and early nodulation of soybean.
      We found that 1.57 mmol ammonium nitrate x L(-1) resulted in less rhizobial
      growth and rhizobial capacity to produce LCOs (on a per cell basis) than did 0.4
      g yeast extract x L(-1), which contained the same amount of N as the ammonium
      nitrate. Increasing yeast extract to 0.8 g x L(-1) increased rhizobial growth and
      LCO production on a volume basis (per litre of culture) and did not affect cell
      capacity to produce LCOs; however, at 1.4 g yeast extract x L(-1) per cell,
      production was reduced. A mixture of 0.8 g yeast extract x L(-1) and 1.6 g casein
      hydrolysate x L(-1) resulted in the greatest bacterial growth and LCO production
      on a volume basis but reduced LCO production per cell. Changes in organic N level
      and source increased production of some of the measured LCOs more than others.
      LCO production was positively correlated with cell density when expressed on a
      volume basis; however, it was negatively correlated on a per cell basis. We
      conclude that although quorum sensing affected Nod factor production, increased
      levels of organic N, and specific compositions of organic N, increased LCO
      production on a volume basis. Greenhouse inoculation experiments showed that the
      medium did not modify nodule number and N fixation in soybean, suggesting that it
      could have utility in inoculant production.

PMID- 16604120
TI  - Technological properties of Enterococcus faecium isolated from ewe's milk and
      cheese with importance for flavour development.
AB  - Eight Enterococcus faecium strains isolated from ewe milk and artisanal cheese
      from northwest Argentina were screened for biotechnological properties relevant
      to flavour development. The API ZYM test showed absence of proteases, presence of
      high amounts of peptidases, and high esterase-lipase activities. Low
      extracellular proteolytic activity was observed. Most strains produced diacetyl
      in milk, with E. faecium OvL 214 and OvL 254 being the best producers. Biomass
      and growth rate increased when citrate was added to the medium, suggesting that
      these strains could use citrate as a main energy source. After 24 h of
      incubation, citrate was completely consumed in complex medium supplemented with
      glucose and citrate. An average of 17% residual citrate was detected in complex
      media supplemented with citrate. For all strains, esterase activity was detected
      up to alpha-naphthyl-caproate. They hydrolyzed alpha-naphthyl derivatives of
      fatty acids in this order: C3 > C6 > C4 > C8 > C2. Post-electrophoretic detection
      of esterase activities revealed the presence of multiple esterases. Hydrolysis of
      tributyrin, tricaprylin, and milk fat was observed in cell-free extracts.
      Enterococcus faecium strains isolated from ewe milk and artisanal cheese from
      northwest Argentina present the metabolic potential to contribute to cheese
      flavour development.

PMID- 16604121
TI  - Bacterial diversity within the planktonic community of an artesian water supply.
AB  - Culture and molecular methods were used to describe the planktonic bacterial
      diversity of an artesian water supply in rural Latah County, Idaho, within the
      drainage of a small perennial stream, Thorn Creek. The surrounding depth to
      groundwater at this location is thought to be significant (>100 m), and this
      transitional zone (basalt-granite) of the Palouse aquifer system is little
      studied. The water produced by this artesian source is consistent even in years
      of drought and is of high quality, both mineralogically and microbiologically. A
      culture-based analysis using 30 media types and four incubation temperatures
      demonstrated that several metabolic types were present in the water. 16S rRNA
      gene fragments amplified from the DNA of pooled cultured cells and from the DNA
      extracted from 1 L of the source water were compared using denaturing gradient
      gel electrophoresis. The results indicated that the two DNA samples did not have
      similar 16S rRNA gene compositions and that several uncultured phyla were present
      in the community DNA sample. These results indicated that large-scale culturing
      did not accurately represent the structure planktonic community. 16S rRNA gene
      sequences from 17 different genera were obtained from the community DNA sample;
      the most abundant were similar to Rhodoferax, Rhodobacter, and Polaromonas
      species. Sequences related to the Proteo bacteria, Bacteroidetes/Chlorobi,
      Firmicutes, and Acidobacterium/Fibrobacter divisions were also detected.

PMID- 16604122
TI  - The Burkholderia cepacia rpoE gene is not involved in exopolysaccharide
      production and onion pathogenicity.
AB  - Burkholderia cepacia was originally described as the causative agent of bacterial
      rot of onions, and it has now emerged as an important opportunistic pathogen
      causing severe chronic lung infections in patients having cystic fibrosis.
      Burkholderia cepacia is now classified into nine very closely related species
      (previously designated as genomovars), all of which have been isolated from both
      environmental and clinical sources and are collectively known as the B. cepacia
      complex. The alternative extracytoplasmic function sigma factor, sigmaE, has been
      determined in several bacterial species as making substantial contributions to
      bacterial survival under stress conditions. Here, we report the identification
      and characterization of the rpoE gene, encoding sigmaE, of B. cepacia. It is
      highly similar to sigmaE of other bacteria, including Escherichia coli and
      Pseudomonas aeruginosa. Studies using an rpoE knockout mutant of B. cepacia
      revealed that many stress adaptations, including osmotic, oxidative, desiccation,
      carbon, and nitrogen stress, were independent of sigmaE. Similarly, biofilm
      formation; production of exopolysaccharides, N-acyl homoserine lactones, and
      several exoenzymes; and onion pathogenicity were not affected by the absence of
      sigmaE. In contrast, sigmaE contributed to the adaptation to heat stress and
      phosphate starvation.

PMID- 16604123
TI  - Isolation and characterization of plaque-purified strains of Malacosoma disstria
      Nucleopolyhedrovirus.
AB  - Seven plaque-purified genotypic variants or strains, derived from a previously
      described field isolate of the Malacosoma disstria Nucleopolyhedrovirus (MadiNPV)
      from Alberta populations of forest tent caterpillar, were characterized based on
      distinctive restriction endonuclease fragment patterns. Two strains, MadiNPV-pp3
      and MadiNPV-pp11, were selected for further characterization, as they represented
      strains producing high and low budded virus (BV) titres, respectively, in the M.
      disstria cell line UA-Md203. Analysis of restriction endonuclease fragment
      profiles indicated the genomes differed significantly in size, 133.8 +/- 2.4 kb
      for MadiNPV-pp3 and 118.1 +/- 3.5 kb for MadiNPV-pp11. These strains were
      characterized based on their BV production in three different cell lines derived
      from M. disstria haemocytes. Compared with MadiNPV-pp11, MadiNPV-pp3 produced two
      to three-fold more BVs in UA-Md203 and 210 other cell lines; however, BV
      production was only marginally higher for MadiNPV-pp3 in the UA-Md221 cell line.
      Similarly, the yield of polyhedral inclusion bodies was significantly higher for
      MadiNPV-pp3 in UA-Md203 and 210 cell lines than for MadiNPV-pp11 but not in the
      UA-Md221 cell line. This data, although derived from a limited number of cell
      lines, suggested MadiNPV-pp3 may have a broader tissue tropism than MadiNPV-pp11.

PMID- 16604124
TI  - PCR detection of pathogenic Leptospira genomospecies targeting putative
      transcriptional regulator genes.
AB  - The genus Leptospira comprises multiple genomospecies that demonstrate varied
      pathogenic potential. The availability of rapid and precise diagnostic procedures
      to differentiate pathogenic from nonpathogenic Leptospira spp. is therefore
      essential to prevent an otherwise easily treatable malaise from developing into a
      life-threatening disease. In this report, we conducted an investigation on the
      diagnostic potential of Leptospira genes encoding putative transcriptional
      regulators. While PCR primers derived from transcriptional regulator gene la1137
      recognized all 24 pathogenic Leptospira strains representing seven species, those
      from la1937, la3231, la3825, and la4130 detected 19 of the 24 Leptospira strains.
      However, none of these primers reacted with four nonpathogenic Leptospira species
      or other common bacteria. The putative transcriptional regulator genes la1137,
      la1937, la3231, la3825, and la4130 are present in pathogenic Leptospira strains,
      making them potential targets for diagnostic applications. Further
      characterization of these genes and their proteins may help elucidate the
      molecular mechanisms of leptospiral virulence and pathogenicity and pave the way
      for potential development of novel control strategies against leptospirosis.

PMID- 16604125
TI  - Power training for older adults.
AB  - Resistance training is widely advocated for older adults to alleviate the muscle
      and strength loss that occurs with aging. While primary and secondary prevention
      of disability are often mentioned as benefits of strength training, the evidence
      for this is limited and inconclusive. Researchers have started to examine another
      form of resistance training that may prove to be more beneficial than strength
      training in terms of the reduction of age-related disability. Power training is
      being investigated because several studies have shown a stronger relationship
      between power and function than between strength and function. Early studies on
      power training suggest that neuromuscular power can be increased to a greater
      extent with high velocity or explosive training than strength training alone. In
      addition, there may be more positive effects on performance tasks measured in the
      laboratory, although evidence on disability reduction was very limited. Adverse
      events were reported in several studies, although the risk for injuries appears
      to be higher for testing than for training itself. Future well-designed studies
      on the risks and benefits of power training should provide more evidence on this
      promising form of resistance training for older adults of varying health and
      functional status.

PMID- 16604126
TI  - The effect of a competitive season and environmental factors on pulmonary
      function and aerobic power in varsity hockey players.
AB  - This study examined the effect of a competitive season and environmental factors
      on pulmonary function and aerobic power in varsity hockey players. Fourteen male
      subjects completed testing before and after a 7-month varsity hockey season
      within ice arena conditions. All subjects completed an aerobic power (.)VO(2)
      (max) test on a cycle ergometer. Pulmonary function tests were performed at rest
      and 1, 10, 15, and 25 min after the (.)VO(2) (max) test. The arena environment
      was monitored during testing and throughout the season for temperature, relative
      humidity, gaseous chemicals, moulds, and fungi. There was no change in (.)VO(2)
      (max) during the season. The percent change in forced expiratory flow in 1 s
      (FEV1) post-exercise compared to resting FEV1 and forced vital capacity (FVC)
      after the (.)VO(2) (max) test were significantly lower after the season. The
      arena temperature and relative humidity ranged between 13 and 16 degrees C and
      between 30% and 45% over the course of the season. Sulfur dioxide (0.7-4.5 ppm)
      was found in the arena and no airborne moulds unique to the dressing room
      environment were found to exceed Health Canada's guideline of 50 CFU/m(3) for
      indoor air quality. It was concluded that some hockey players experience
      limitations to pulmonary function over the course of a competitive season.

PMID- 16604127
TI  - Effect of glycerol-induced hyperhydration on thermoregulatory and cardiovascular
      functions and endurance performance during prolonged cycling in a 25 degrees C
      environment.
AB  - We compared the effect of glycerol-induced hyperhydration (GIH) to that of water
      induced hyperhydration (WIH) on cardiovascular and thermoregulatory functions and
      endurance performance (EP) during prolonged cycling in a temperate climate in
      subjects consuming fluid during exercise. At weekly intervals, 6 trained male
      subjects ingested, in a randomized, double-blind, counterbalanced fashion, either
      a glycerol (1.2 g glycerol/kg bodyweight (BW) with 26 mL/kg BW of water-aspartame
      flavored fluid) or placebo solution (water-aspartame-flavored fluid only) over a
      2 h period. Subjects then performed 2 h of cycling at 66% of the maximal oxygen
      consumption (VO(2) max) and 25 degrees C while drinking 500 mL/h of sports drink,
      which was followed by a step-incremented cycling test to exhaustion. Levels of
      hyperhydration did not differ significantly between treatments before exercise.
      During exercise, GIH significantly reduced urine production by 246 mL. GIH did
      not increase sweat rate nor did it decrease heart rate, rectal temperature, or
      perceived exertion during exercise as compared with WIH. EP was not significantly
      different between treatments. Neither treatment induced undesirable side effects.
      It is concluded that, compared with WIH, GIH decreases urine production, but does
      not improve cardiovascular or thermoregulatory functions, nor does it improve EP
      during 2 h of cycling in a 25 degrees C environment in trained athletes consuming
      500 mL/h of fluid during exercise.

PMID- 16604128
TI  - Central and peripheral factors in thermal, neuromuscular, and perceptual
      adaptation of the hand to repeated cold exposures.
AB  - We investigated the role of central and peripheral factors in repeated cold
      exposure of the hand and their effects on temperature response, neuromuscular
      function, and subjective thermal sensation. Eleven subjects immersed their left
      hand repeatedly in 8 degrees C cold water for 30 min, 5 d/week, for 2 weeks.
      Before and following the 2 weeks of exposure, neuromuscular function, blood
      markers, thermal sensation, and temperature responses of both acclimated (left)
      and control (right) hands were tested. Minimum index finger temperature pre
      acclimation was 10.9 +/- 3.4 degrees C and 10.0 +/- 2.0 degrees C in the left and
      right hand, respectively, and did not change significantly post-acclimation
      (left, 12.8 +/- 4.2 degrees C; right, 10.2 +/- 1.1 degrees C). Neuromuscular
      function was impaired with cooling, but this was significantly different neither
      between the hands nor over time. Central factors, measured by catecholamines and
      changes in temperature and cardiovascular response over time, did not change and
      there were no differences in responses between the exposed and non-exposed hand
      over time (peripheral adaptation) nor were there any differences in local factors
      endothelial-1 and nitric oxide. Subjective thermal comfort was improved and the
      discrepancy that was found between the change in actual and perceived temperature
      may increase the risk of cold injury in partially acclimatized individuals, owing
      to an adjustment in behavioural thermoregulation.

PMID- 16604129
TI  - Objective and subjective analysis of the training content in young cyclists.
AB  - The purpose of this study was to analyse the objective and subjective training
      for young cyclists that is prescribed by their coaches. Seven cyclists performed
      an incremental exercise to exhaustion before and after 14 weeks of training using
      an incremental test to determine their maximal oxygen uptake (VO(2) (max)), the
      velocity associated with VO(2) (max) (vVO(2) (max)), and the velocity associated
      with the ventilatory threshold (vVT). Cyclists completed a training record with
      the actual content and the perceived exertion of each training session during
      these 14 weeks. We have focused on the actual content of the training prescribed
      by the coaches. Analysis of the content of each session allowed us to calculate
      the objective training load (volume at different intensities) and to determine
      the subjective training load from perceived exertion ratings (training load,
      monotony, strain, and fitness-fatigue). The results showed that cyclists were
      training at a relatively low intensity and that training rating of perceived
      exhaustion was weak. Moreover, after 14 weeks of training, VO2 max did not change
      whereas vVO(2) (max) and vVT increased significantly. Therefore, a discrepancy
      may exist between what is perceived during training and the effects of training.
      Consequently, objective and subjective indices collected from training books
      provided useful information supplementary to that recorded from the physiological
      indices alone.

PMID- 16604130
TI  - Light concentric exercise has a temporarily analgesic effect on delayed-onset
      muscle soreness, but no effect on recovery from eccentric exercise.
AB  - This study investigated the hypothesis that a bout of light concentric exercise
      (LCE) would alleviate delayed-onset muscle soreness (DOMS) and enhance recovery
      from muscle damage. Fourteen subjects performed two bouts of 60 maximal eccentric
      actions of the elbow flexors (Max-ECC) separated by 2-4 weeks. One arm performed
      LCE (600 elbow flexion and extension actions with minimal force generation) 1, 2,
      3, and 4 d after Max-ECC; the contralateral (control) arm performed only Max-ECC.
      Changes in maximal isometric and isokinetic strength, range of motion (ROM),
      upper arm circumference, and muscle soreness and tenderness were assessed before
      and immediately after LCE bouts. Changes in these measures and plasma creatine
      kinase (CK) activity for 7 d after Max-ECC were compared between the control and
      LCE arms using 2-way repeated measures analysis of variance (ANOVA). Significant
      (p < 0.05) decreases in muscle soreness (approximately 40%) and tenderness
      (approximately 40%) were evident immediately after LCE, which also resulted in
      small but significant decreases in strength (approximately 15%) and increases in
      ROM (approximately 5 degrees ). No significant differences in the changes in the
      measures following Max-ECC were observed between the arms. These results suggest
      that LCE has a temporary analgesic effect on DOMS, but no effect on recovery from
      muscle damage.

PMID- 16604131
TI  - The effect of desmopressin, a vasopressin analog, on endurance performance during
      a prolonged run in simulated heat conditions.
AB  - Arginine vasopressin (AVP) release into the bloodstream is essential for water
      balance in the body and, thus, for core-temperature regulation. We investigated
      the effect of the AVP analog desmopressin (Des) on the performance of 6 endurance
      runners in a simulated heat condition. Four strenuous treadmill runs were
      performed at a 1-week interval. Over the 4 test sessions, room temperature and
      relative humidity were 22 +/- 0.4 degrees C and 47% +/- 7%, respectively. Each
      run included 40 min at 60% maximal aerobic velocity immediately followed by an
      incremental run until exhaustion. Dehydration and hyperthermia were induced by
      wearing an impermeable tracksuit. Two runs were performed with no hydration (NH;
      NH-Des) and two under false hydration (FH; FH-Des). Under FH conditions, the
      runner was given a set amount of water every 5 min of the run, which was kept in
      the mouth for 10 s and spat out. Under NH-Des and FH-Des conditions, the run was
      performed 60 min after a 30 microg intranasal administration of desmopressin. In
      the NH-Des trial, the total distance run was 5%-8% longer than in the other
      conditions (p < 0.05). This was associated with a lower heart rate after the 40
      min run than occurred in the NH and FH trials (p < 0.01) and a lower tympanic
      temperature than in the FH trial (p < 0.05). Urine mass was also lower under NH
      Des conditions than under NH and FH conditions (p < 0.05). It is suggested that
      desmopressin administration could improve dramatically prolonged running
      performances in a hot and humid environment.

PMID- 16604132
TI  - Estimating energy expenditure for brief bouts of exercise with acute recovery.
AB  - Four indirect estimations of energy expenditure were examined, (i) O(2) debt,
      (ii) O(2) deficit, (iii) blood lactate concentration, and (iv) excess CO(2)
      production during and after 6 exercise durations (2, 4, 10, 15, 30, and 75 s)
      performed at 3 different intensities (50%, 100%, and 200% of VO(2) max). Analysis
      of variance (ANOVA) was used to determine if significant differences existed
      among these 4 estimations of anaerobic energy expenditure and among 4 estimations
      of total energy expenditure (that included exercise O(2) uptake and excess post
      exercise oxygen consumption, or EPOC, measurements). The data indicate that
      estimations of anaerobic energy expenditure often differed for brief (2, 4, and
      10 s) bouts of exercise, but this did not extend to total energy expenditure. At
      the higher exercise intensities with the longest durations O(2) deficit, blood
      lactate concentration, and excess CO(2) estimates of anaerobic and total energy
      expenditure revealed high variability; however, they were not statistically
      different. Moreover, they all differed significantly from the O(2) debt
      interpretation (p < 0.05). It is concluded that as the contribution of rapid
      substrate-level ATP turnover with lactate production becomes larger, the greatest
      error in quantifying total energy expenditure is suggested to occur not with the
      method of estimation, but with the omission of a reasonable estimate of anaerobic
      energy expenditure.

PMID- 16604133
TI  - Effects of a high-intensity swim test on kinematic parameters in high-level
      athletes.
AB  - The present study aimed to investigate the effects of a high-intensity swim test
      among top-level swimmers on (i) the spatial and temporal parameters of both the
      stroke and the 3-D fingertip pattern and (ii) the mechanical, muscular, and
      physiological parameters. Ten male international swimmers performed a 4 x 50 m
      swim at maximal intensity. Isometric arm flexion force with the elbow at 90
      degrees (F90 degrees ), EMG signals of right musculus biceps brachii and triceps
      brachii and blood lactate concentrations were recorded before and after the swim
      test. Kinematic stroke (stroke length, rate, and velocity) and spatiotemporal
      parameters of the fingertip trajectory were measured by two underwater cameras
      during the first and last 50 m swims. After the swim test, F90 degrees and mean
      power frequencies of the EMG decreased significantly when blood lactate
      concentration increased significantly, attesting the reaching of fatigue. From
      the first to the last 50 m, stroke rate, stroke velocity, and temporal parameters
      of the fingertip trajectory exhibited significant increases although stroke
      length and spatial fingertip trajectory remained unchanged. General and
      individual adaptations were observed among the top-level swimmers studied. The
      present findings could be useful for coaches in evaluating fatigue effects on the
      technical parameters of swimming.

PMID- 16604134
TI  - Variable effects of respiratory muscle training on cycle exercise performance in
      men and women.
AB  - Respiratory muscle training (RMT) has been proposed as an effective means to
      increase the strength of the inspiratory muscles and improve exercise
      performance. The purpose of this study was to examine the effect of RMT on
      cycling time to exhaustion (TTE) and to determine any potential sex effect. We
      hypothesized that RMT would improve maximal inspiratory pressure (MIP) and TTE to
      a similar degree in men and women. Males (n = 7; mean (+/- SD) age, 22.1 +/- 1.5
      y) and females (n = 8; mean (+/- SD) 24.5 +/- 4.9 y) performed an incremental
      cycle test to determine maximal oxygen consumption ((.)VO(2) (max)) (day 1),
      followed by a familiarization TTE (day 2) and baseline TTE (day 3) at 80% maximal
      work achieved during the ((.)VO(2) (max)) test. Subjects then completed 5 weeks
      of respiratory muscle training (RMT) (5 d/week, 2 sets of 30 inspirations against
      50% MIP). Four training sessions per week were performed at home and the 5th was
      supervised, during which the threshold load was increased if necessary. Following
      RMT, subjects completed 2 TTE tests (days 4 and 5). MIP increased in each subject
      (37% +/- 18%, P < 0.05). There was no difference between men (pre = -100 +/- 20
      vs. post = -140 +/- 29 cmH(2)O) and women (pre = -90 +/- 28 vs. post = -117 +/-
      28 cmH(2)O). Baseline TTE (male = 301 +/- 122 s; female = 338 +/- 98 s) was
      shorter in comparison with the best of the 2 TTE-post tests (male = 353 +/- 68 s;
      female = 416 +/- 116 s; P < 0.01), but not when compared with days 4 or 5 (P >
      0.05). RMT increases MIP and may improve exercise performance; however,
      improvements are variable with no differences between men and women.

PMID- 16604135
TI  - Stereological analysis of muscle morphology following exposure to repetitive
      stretch-shortening cycles in a rat model.
AB  - Repetitive motion is one risk factor associated with contraction-induced muscle
      injury, which leads to skeletal muscle degeneration, inflammation, and
      dysfunction. Since current methods are unable to quantify the acute degenerative
      and inflammatory responses of muscle tissue concurrently, the purpose of this
      study was to quantify the temporal myofiber response after exposure to injurious
      stretch-shortening cycles (SSCs) using a standardized stereological technique.
      Functional testing was performed on the ankle dorsiflexor muscles of Sprague
      Dawley rats in vivo. Rats were anesthetized and exposed to 15 sets of 10 SSCs.
      Control rats were exposed to 15 sets of single isometric contractions of the same
      stimulation duration. Changes in muscle morphometry were assessed at 0.5, 24, 48,
      72, and 240 h post-exposure to quantify the degree of myofiber degeneration and
      inflammation in the tibialis anterior muscle from each group. There was an
      increase in the volume density and average thickness of degenerating myofibers
      over time in the muscle collected from rats exposed to SSCs (p < 0.0001) that was
      significantly greater than in muscle exposed to isometric contractions at 24, 48,
      and 72 h post-exposure (p = 0.003). The volume density of degenerative myofibers
      was associated with functional deficits at 48 h. Stereological quantification of
      degenerative myofibers and interstitial space changes were associated with
      functional defects 48-72 h after SSC-induced injury, thus demonstrating
      stereology is an accurate measure of SSC-induced skeletal muscle injury.

PMID- 16604136
TI  - Physiological adaptation in early human pregnancy: adaptation to balance maternal
      fetal demands.
AB  - After conception, the corpus luteum, placenta, and developing embryo release
      hormones, growth factors, and other substances into the maternal circulation.
      These substances trigger a cascade of events that transform the functioning of
      the maternal cardiovascular, respiratory, and renal systems, which in turn alter
      the physicochemical determinants of [H(+)]. Following implantation, maternal
      adaptations fulfill 4 important functions that support fetal growth. Increased
      availability of substrates and precursors for fetal-placental metabolism and
      hormone production is mediated by increases in dietary intake, as well as
      endocrine changes that increase the availability of glucose and low-density
      lipoprotein (LDL) cholesterol. Transport capacity is enhanced by increases in
      cardiac output, facilitating the transport of substrates and precursors to the
      placenta, and fetal waste products to maternal organs for disposal. Maternal
      fetal exchange is regulated by the placenta after 10-12 weeks gestation, but it
      may occur through histiotrophic mechanisms before this time. Disposal of
      additional waste products (heat, carbon dioxide, and metabolic byproducts) occurs
      through peripheral vasodilation and increases in skin blood flow, ventilation,
      and renal filtration. The maternal physiological adaptations described above must
      meet the combined demands of maternal exercise and fetal growth. More research is
      needed to formulate evidence-based guidelines for healthy physical activity in
      early pregnancy.

PMID- 16604137
TI  - Nutrition for healthy pregnancy outcomes.
AB  - Many healthcare professionals and their patients are aware of the importance of
      proper nutrition during pregnancy, but may not be aware of specific nutritional
      recommendations on how to achieve a healthy pregnancy outcome. This review
      article aims to discuss the implications maternal nutritional status and weight
      gain have in both the short and long terms. Babies born to mothers with
      inadequate weight gain are more likely to be premature and small for gestational
      age (SGA). They are also predisposed to obesity and metabolic problems later in
      life. Women with excessive weight gain during pregnancy are at increased risk for
      developing type II diabetes later in life. Their offspring also have increased
      body fat as babies and during childhood. Pregnant women need to be informed about
      appropriate weight gain and how to achieve this, and should be given specific
      nutritional recommendations and weight-gain goals.

PMID- 16604138
TI  - What can metabolic myopathies teach us about exercise physiology?
AB  - Exercise physiologists are interested in metabolic myopathies because they
      demonstrate how knocking out a component of a specific biochemical pathway can
      alter cellular metabolism. McArdle's disease (myophosphorylase deficiency) has
      often been studied in exercise physiology to demonstrate the influence of
      removing the major anaerobic energy supply to skeletal muscle. Studies of
      patients with McArdle's disease have shown the increased reliance on blood-borne
      fuels, the importance of glycogen to maximal aerobic capacity, and the use of
      nutritional strategies to bypass metabolic defects. Myoadenylate deaminase
      deficiency is the most common metabolic enzyme deficiency in human skeletal
      muscle. It is usually compensated for endogenously and does not have a major
      influence on high-energy power output. Nutritional interventions such as
      carbohydrate loading and carbohydrate supplementation during exercise are
      essential components of therapy for patients with fatty acid oxidation defects.
      Cases of mitochondrial myopathies illustrate the importance of peripheral oxygen
      extraction for maximal aerobic capacity and show how both exercise and
      nutritional interventions can partially compensate for these mutations. In
      summary, metabolic myopathies provide important insights into regulatory and
      nutritional aspects of the major biochemical pathways of intermediary metabolism
      in human skeletal muscle.

PMID- 16604139
TI  - Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human
      skeletal muscle.
AB  - In the past decade, a family of monocarboxylate transporters (MCTs) have been
      identified that can potentially transport lactate, pyruvate, ketone bodies, and
      branched-chain ketoacids. Currently, 14 such MCTs are known. However, many orphan
      transporters exist that have transport capacities that remain to be determined.
      In addition, the tissue distribution of many of these MCTs is not well defined.
      Such a cataloging can, at times, begin to suggest the metabolic role of a
      particular MCT. Recently, a number of antibodies against selected MCTs (MCT1, -2,
      -4, and -5 to -8) have become commercially available. Therefore, we examined the
      protein expression of these MCTs in a large number of rat tissues (heart,
      skeletal muscle, skin, brain, testes, vas deferens, adipose tissue, liver,
      kidney, spleen, and pancreas), as well as in human skeletal muscle. Unexpectedly,
      many tissues coexpressed 4-5 MCTs. In particular, in rat skeletal muscle MCT1,
      MCT2, MCT4, MCT5, and MCT6 were observed. In human muscle, these same MCTs were
      present. We also observed a pronounced MCT7 signal in human muscle, whereas a
      very faint signal occurred for MCT8. In rat heart, which is an important
      metabolic sink for lactate, we confirmed that MCT1 and -2 were expressed. In
      addition, MCT6 and -8 were also prominently expressed in this tissue, although it
      is known that MCT8 does not transport aromatic amino acids or lactate. This
      catalog of MCTs in skeletal muscle and other tissues has revealed an unexpected
      complexity of coexpression, which makes it difficult to associate changes in
      monocarboxylate transport with the expression of a particular MCT. The
      differences in transport kinetics for lactate and pyruvate are only known for
      MCT1, -2 and -4. Transport kinetics remain to be established for many other MCTs.
      In conclusion, this study suggests that in skeletal muscle, as well as other
      tissues, lactate and pyruvate transport rates may not only involve MCT1 and -4,
      as other monocarboxylate transporters are also expressed in rat (MCT2, -5, -6)
      and human skeletal muscle (MCT2, -5, -6, -7).

PMID- 16604140
TI  - Physical activity and the metabolic syndrome in Canada.
AB  - The metabolic syndrome (MetS) is a cluster of risk factors that predispose
      individuals to cardiovascular disease. Therapeutic lifestyle changes, including
      increased physical activity, are recommended for the prevention and treatment of
      MetS. The purpose of this study was to examine the relationship between physical
      activity and MetS in Canada. The sample included 6406 men and 6475 women aged 18
      64 y who were participants in the Canadian Heart Health Surveys (1986-1992). MetS
      was classified using criteria modified from the US National Cholesterol Education
      Program. Participants were deemed physically active if they were active at least
      once each week for at least 30 min, engaging in strenuous activity some of the
      time. The relationship between physical activity and MetS was assessed using
      logistic regression, with age, smoking, alcohol consumption, and income adequacy
      as covariates. A total of 14.4% of Canadians had MetS and 33.6% were physically
      active. The odds ratio for MetS was 0.73 (95% confidence interval (CI): 0.54
      0.98; p < 0.05) for physically active vs. physically inactive participants. The
      corresponding odds ratios were 0.45 (95% CI: 0.29-0.69; p < 0.001) and 0.67 (95%
      CI: 0.44-1.02; p = 0.06) for men and women, respectively. In summary, physical
      activity was associated with lower odds of MetS, particularly in men. Further
      research is required to determine the effectiveness of physical activity in the
      treatment of MetS.

PMID- 16604141
TI  - Vastus lateralis oxygenation during prolonged cycling in healthy males.
AB  - This study examined the relationship between acute cardiorespiratory and muscle
      oxygenation and blood volume changes during prolonged exercise. Eight healthy
      male volunteers (mean maximum oxygen uptake VO(2max) = 41.6 +/- 2.4 mL/kg/min)
      performed 60 min submaximal cycling at 50% VO(2max). Oxygen uptake VO(2) was
      measured by indirect spirometry, cardiac output (CO) was estimated using a
      Portapre, and right vastus lateralis oxyhemoglobin/ myoglobin (oxyHb/Mb),
      deoxyhemoglobin/myoglobin (deoxyHb/Mb), and total hemoglobin/myoglobin (total
      Hb/Mb) were recorded using near-infrared spectroscopy (NIRS). After 40 min of
      exercise, there was a significant increase in VO(2) due to a significantly higher
      arteriovenous oxygen difference ((a - v)O(2diff). After 30 min of exercise CO
      remained unchanged, but there was a significant decrease in stroke volume and a
      proportionate increase in heart rate, thus indicating the occurrence of
      cardiovascular drift. During the first few minutes of exercise, there was a
      decline in oxyHb/Mb and total Hb/Mb, whereas deoxyHb/Mb remained unchanged.
      Thereafter, oxyHb/Mb and total Hb/Mb increased systematically until the
      termination of exercise while deoxyHb/Mb declined. After 40 min of exercise,
      these changes were significantly different from the baseline values. There were
      no significant correlations between the changes in the NIRS variables and
      systemic VO(2) or mixed (a - v)O(2)diff during exercise. These results suggest
      that factors other than localized changes in muscle oxygenation and blood volume
      account for the increased VO(2) during prolonged submaximal exercise.

PMID- 16604143
TI  - Symposium overview. Dietary Reference Intakes: considerations for physical
      activity.
AB  - The following series of papers comprise a symposium on Dietary Reference Intakes
      (DRIs), which are the new dietary recommendations for North Americans, that was
      presented at the 2004 Annual Meeting of the Canadian Society for Exercise
      Physiology. The process of developing the DRIs has been an enormous undertaking
      resulting, thus far, in 12 book-length reports spanning from 1997 to 2004. It was
      therefore timely to review the recommendations, describe the considerations for
      physical activity that went into setting the recommendations, and, where
      possible, indicate how the DRIs may be applied to athletes.

PMID- 16604144
TI  - Introduction to dietary reference intakes.
AB  - Dietary Reference Intakes (DRIs) are nutrient reference standards used for
      planning and assessing the diets of apparently healthy Canadians and Americans.
      The development of DRIs reflects a joint initiative by the United States and
      Canada to update, expand on, and replace the former Recommended Nutrient Intakes
      for Canadians and Recommended Dietary Allowances for Americans. DRIs include the
      Estimated Average Requirement (EAR), Recommended Dietary Allowance (RDA),
      Adequate Intake (AI), and Tolerable Upper Intake Level (UL). The EAR is the
      average daily intake level that meets the requirement of 50% of healthy
      individuals in a life stage and gender group, whereas the RDA is set at a level
      that will meet the requirements of almost all (97%-98%) individuals in that life
      stage and gender group. An AI is a recommended intake level that is thought to
      meet the needs of almost all healthy individuals, and is set when there are
      insufficient data to establish an EAR (and therefore an RDA). The UL represents a
      threshold above which adverse effects of excessive intake may increase. In
      addition to these DRIs, macro nutrients have an Acceptable Macro nutrient
      Distribution Range (AMDR) and, for energy, an Estimated Energy Requirement (EER)
      is described.

PMID- 16604145
TI  - Applications of Dietary Reference Intakes in dietary assessment and planning.
AB  - Dietary Reference Intakes (DRIs) are used for assessing and planning diets of
      individuals and groups. Assessing individual intakes is complicated by the fact
      that neither the individual's usual nutrient intake nor their individual
      requirement is known. However, the degree of confidence that intakes are adequate
      or excessive can be estimated. Assessing diets of groups requires information on
      the group's usual nutrient intake distribution, which can be obtained by
      statistically adjusting 1 d intake distributions to remove within-person
      variability. For most nutrients with an Estimated Average Requirement (EAR), the
      group prevalence of inadequate intakes can be approximated by the percent whose
      usual intakes are less than the EAR. However, the prevalence of inadequacy cannot
      be determined for nutrients with an Adequate Intake (AI). The goals of planning
      are a low risk (for individuals) or low prevalence (for groups) of inadequate or
      excessive nutrient intakes. For individuals, these goals are met by planning
      intakes that meet the Recommended Dietary Allowance (RDA) or AI, are below the
      Tolerable Upper Intake Level (UL), and fall within the Acceptable Macronutrient
      Distribution Ranges (AMDRs). For groups, planning involves estimating a "target"
      usual intake distribution with an acceptably low prevalence less than the EAR and
      greater than the UL, planning menus to achieve the target distribution, and
      assessing the results.

PMID- 16604146
TI  - Dietary Reference Intakes for the macronutrients and energy: considerations for
      physical activity.
AB  - The Dietary Reference Intakes (DRIs) are the North American reference standards
      for nutrients in the diets of healthy individuals. The macronutrient DRI report
      includes the standards for energy, fat and fatty acids, carbohydrate and fiber,
      and protein and amino acids. Equations used to identify the Estimated Energy
      Requirement (EER) were also developed based on individual characteristics
      including levels of physical activity. The DRIs for the macronutrients are
      presented as Recommended Dietary Allowances (RDAs) or Adequate Intakes (AIs), as
      well as Acceptable Macronutrient Distribution Ranges (AMDRs), and were arrived at
      by considering both nutrient inadequacies and excesses. In addition,
      recommendations are made that would reduce the risk of chronic diseases, such as
      setting intake limits for added sugar; reducing cholesterol, saturated, and trans
      fatty acids consumption; and increasing levels of physical activity. As healthy
      individuals include those engaged in various levels of physical activity, the
      DRIs should apply to the athlete and address their macronutrient and energy
      needs. This paper summarizes the macronutrient DRI report as applied to the
      adult, with discussion of the dietary needs of those engaged in various levels of
      physical activity, including the athlete.

PMID- 16604147
TI  - Dietary Reference Intakes for the micronutrients: considerations for physical
      activity.
AB  - The Dietary Reference Intakes (DRIs) are a set of recommendations for healthy
      persons. For the most part, recommendations are determined experimentally under
      controlled conditions of light activity. During increased physical activity, it
      is expected that micronutrient requirements would increase relative to the
      inactive state. Micronutrients of interest to athletes are those associated with
      oxygen handling and delivery, such as iron, and vitamin D, a newly emerging
      function of which is to maintain muscle strength. The DRI report on electrolytes
      (including water) is the most recent set of recommendations. In addition to
      recommendations for intakes to meet needs, many micronutrients have an upper
      level that indicates caution in consuming a large amount. We illustrate the
      process of setting DRI values for the micronutrients (including electrolytes and
      water), and provide a summary of instances where physical activity needs were
      considered when DRI values were derived. Understanding the origin of DRI values
      for micronutrients will assist in understanding how to use the values in
      assessment and planning.

PMID- 16604148
TI  - Recent achievements in in vitro culture and preservation of ovarian follicles in
      mammals.
AB  - The mammalian ovary contains a large number of follicles that are in various
      developmental stages. The largest portion of them are primordial follicles.
      However, throughout the female reproductive lifespan only a small proportion of
      these follicles will produce oocytes competent to undergo successful maturation
      and ovulation. The rest of the ovarian oocytes (>99.9%) undergo atresia. It would
      be of great practical benefit to rescue some of these follicles by growing them
      in culture in order to provide an extra source of gametes. There is considerable
      interest in developing technologies that aim to produce fully-grown,
      developmentally competent oocytes from a pool of early developmental stages of
      follicles. Two methods have been used: 1/ long-term in vitro culture of either
      follicles or oocytes, and 2/ transplantation of ovarian tissue grafts. The
      development of efficient technologies may provide an additional source of oocytes
      for livestock production and reproduction in humans and rare or endangered
      species. The aim of this paper is to present a comprehensive review of recent
      achievements in the utilization of small ovarian follicles (primordial, preantral
      and early antral) by long-term in vitro culture and/or transplantation of ovarian
      tissue grafts (fresh and cryopreserved) in mammals including humans.

PMID- 16604149
TI  - Cadmium toxicity: a possible cause of male infertility in Nigeria.
AB  - Serum and seminal plasma cadmium (Cd) concentrations were estimated by atomic
      absorption spectrophotometry in 60 infertile adult male Nigerians (40
      oligozoospermics and 20 azoospermics). The results were compared with Cd level in
      40 normozoospermic subjects (matched age, with proven evidence of fertility). The
      relationship between Cd levels and spermatograms or the hypothalamic-pituitary
      gonadal (HPG) -axis was investigated by correlating serum and seminal plasma Cd
      levels with semen characteristics and hormone levels. The seminal plasma Cd level
      was significantly higher than those of serum in all studied groups (p<0.001). The
      serum and seminal plasma Cd levels were increased (p<0.001) in azoospermics in
      comparison to oligozoospermic and control subjects. A significant negative
      correlation was observed between serum Cd level and all examined biophysical
      semen characteristics except sperm volume. A positive correlation was also
      observed between seminal plasma Cd and FSH. Results of the study for the first
      time implicate cadmium as a cause of infertility in male Nigerians as well as
      extend and support previous findings concerning cadmium toxicity and male
      infertility. The strong deleterious effect of cadmium on spermatogenesis may be
      due to the systemic and cellular toxicity. A possible relationship between this
      element and the HPG axis is also suggested.

PMID- 16604150
TI  - Effect of genistein on steroidogenic response of granulosa cell populations from
      porcine preovulatory follicles.
AB  - Genistein affects reproductive processes in animals. However, the mechanism of
      its action is not fully elucidated and differs among species. The objectives of
      the current study were: 1/ to establish an in vitro model of granulosa cell
      culture for studying the intracellular mechanism of phytoestrogen action in
      porcine ovary; 2/ to determine an in vitro effect of genistein on basal and FSH
      stimulated P(4) and E(2) production by porcine granulosa cell populations
      (antral, mural, total) isolated from large, preovulatory follicles. Granulosa
      cells were isolated from large (> or =8 mm), preovulatory follicles and separated
      into antral and mural cell subpopulations. Cells were allowed to attach for 72 h
      (37 degrees Celsius, 10% serum, 95% air/5% CO2) and than cultured for next 48
      hours with or without serum (0, 5 and 10%), FSH (0, 10 or 100 ng/ml) and
      genistein (0, 0.5, 5 or 50 microM). Basal P(4) and E(2) production did not differ
      among antral, mural and unseparated granulosa cells isolated form porcine
      preovulatory follicles. Only mural cells tended to secrete less P(4) and E(2)
      than other cell populations. FSH stimulated P(4) production in a dose dependent
      manner in all cell populations and culture systems. Genistein inhibited in a dose
      dependent manner basal and FSH-stimulated P(4) production by antral, mural and
      unseparated granulosa cells. However, genistein did not affect E(2) production by
      granulosa cells. In addition, viability of porcine granulosa cells was not
      affected by the pyhytoestrogen except the highest dose of genistein. It appears
      that genistein may be involved in the regulation of follicular function in pigs.
      Moreover, unseparated porcine granulosa cells may provide a suitable in vitro
      model for studying the intracellular mechanism of phytoestrogen action in porcine
      ovary.

PMID- 16604151
TI  - Effect of P.G. 600 on rebreeding performance in sows limit-fed during lactation.
AB  - The objective was to determine whether treatment with 400 IU PMSG and 200 IU hCG
      (P.G. 600; Intervet America, Inc., Millsboro, DE, USA) at weaning improved
      rebreeding performance in sows that were limit-fed during lactation. Crossbred
      sows were allowed ad libitum access to feed or were limited to 3.2 kg of feed/day
      during an 18-day lactation. At weaning, limit-fed sows received im treatment with
      P.G. 600 (n = 16) or saline (n = 19) and ad libitum-fed sows received saline (n =
      18). The percentage of sows in estrus by day 7 post-weaning was greater (p<0.05),
      and the weaning-to-estrus interval was shorter (p<0.05), for ad libitum-fed sows
      compared to limit-fed, saline-treated sows, with limit-fed, P.G. 600-treated sows
      having intermediate values that were not different from the other two groups. The
      percentage of sows pregnant and the numbers of corpora lutea and embryos at day
      30 post-mating were not different (p>0.1) among groups. In summary, low feed
      intake during lactation decreased the percentage of sows that displayed estrus
      within 7 days after weaning and increased the weaning-to-estrus interval. These
      effects were at least partially remediated by gonadotropin treatment. Pregnancy
      rate, and litter size at day 30 of gestation, were similar for ad libitum- and
      limit-fed sows and not affected by P.G. 600 treatment in limit-fed sows.

PMID- 16604152
TI  - Effect of early thermal experience on pituitary-gonadal axis in female rats.
AB  - The reproductive system fully develops during postnatal stages of life, and as
      such it may be susceptible to environmental cues such as high temperature. Thus,
      the purpose of the study was to compare how exposure to 34 degrees Celsius
      ambient temperature affects pituitary-gonadal axis of immature and adult female
      rats. Three groups of females at proestrous or metaestrous (n=38) were used in
      the study. The females were housed in ambient temperature of 34 degrees Celsius
      (WR group, n=10) or room temperature (CR group, n=16) from birth to adulthood.
      The females from the third group were acclimated to 34 degrees Celsius as adults
      (WA group, n=12). In the WR group the onset of puberty was delayed in comparison
      to the CR group. The plasma PRL level was lower during proestrous and higher
      during metaestrous in the WR group compared to the CR group. During metaestrous,
      lower FSH and higher progesterone (P(4)) plasma concentrations were found in the
      WR females. No changes in LH and oestradiol (E(2)) plasma concentrations were
      demonstrated. Higher in vitro E(2) and lower P(4) secretions under FSH
      stimulation were observed in the WR follicles compared to those of the CR group.
      The WR group also demonstrated higher basal and LH-stimulated luteal in vitro
      secretion of P(4) than controls. Plasma LH and FSH concentrations during
      metaestrous were higher in WA females than in the WR group, but PRL level was
      lower. Follicles of the WA group were unresponsive to FSH with respect to steroid
      secretion. In addition, LH stimulated luteal E(2) secretion in this group. P(4)
      release by luteal cells was lower in the WA than in the WR group. We concluded
      that WR females differ from WA in reproductive system adjustments to rearing
      temperature and that early thermal experience is more effective in antagonizing
      the effect of high temperature than acclimation of adult females.

PMID- 16604153
TI  - Biochemical and immunochemical characterization of boar sperm flagellar protein
      with role in hyperactivation/capacitation process.
AB  - Investigations on specific and functionally active sperm antigens could bring
      about the elucidation of the mechanisms of gamete interaction and help the search
      for new approaches in prognosis and regulation of fertility. Previously, we
      reported that the monoclonal antibody (Mab) 3G4 against capacitated boar
      spermatozoa was capable of inhibiting boar sperm-porcine zona pellucida binding
      due to its inhibitory effect on sperm hyperactivation and capacitation. The cell
      and tissue specificity of Mab 3G4 was demonstrated in indirect immunofluorescence
      (IIF) and ELISA experiments against spermatozoa from different vertebrate
      species, as well as against extracts of boar reproductive and somatic organs. In
      the present IIF experiments, it was shown that Mab 3G4 recognized an antigen
      determinant on the flagellar midpiece region of ejaculated and capacitated boar
      spermatozoa. It was speculated that the Mab 3G4-corresponding antigen
      participates in pyruvate/lactate metabolism because of its specific localization
      in the sperm structure, which is responsible for producing forward motility and
      its involvement in processes that require the metabolism of pyruvate and lactate.
      As a possible approach toward investigating the participation of Ag 3G4 in
      pyruvate/lactate metabolism, Mab 3G4's effect on lactate dehydrogenase (LDH) was
      examined. Using an electrophoretic approach we provided evidence that Mab 3G4
      stimulates LDH activity in the Triton X-100 and NP40 protein fractions of
      capacitated boar spermatozoa. In addition, we found that LDH isoenzymes
      stimulated by Mab 3G4 are of gametic C type. In Western blot, under nonreducing
      conditions, Mab 3G4 identified a single protein band with a molecular weight of
      140 kDa. The biochemical and immunochemical experiments provided evidence
      supporting the involvement of 3G4 antigen in the sperm pyruvate/lactate
      metabolism.

PMID- 16604154
TI  - An antivector vaccine protects against a lethal vector-borne pathogen.
AB  - Vaccines that target blood-feeding disease vectors, such as mosquitoes and ticks,
      have the potential to protect against the many diseases caused by vector-borne
      pathogens. We tested the ability of an anti-tick vaccine derived from a tick
      cement protein (64TRP) of Rhipicephalus appendiculatus to protect mice against
      tick-borne encephalitis virus (TBEV) transmitted by infected Ixodes ricinus
      ticks. The vaccine has a "dual action" in immunized animals: when infested with
      ticks, the inflammatory and immune responses first disrupt the skin feeding site,
      resulting in impaired blood feeding, and then specific anti-64TRP antibodies
      cross-react with midgut antigenic epitopes, causing rupture of the tick midgut
      and death of engorged ticks. Three parameters were measured: "transmission,"
      number of uninfected nymphal ticks that became infected when cofeeding with an
      infected adult female tick; "support," number of mice supporting virus
      transmission from the infected tick to cofeeding uninfected nymphs; and
      "survival," number of mice that survived infection by tick bite and subsequent
      challenge by intraperitoneal inoculation of a lethal dose of TBEV. We show that
      one dose of the 64TRP vaccine protects mice against lethal challenge by infected
      ticks; control animals developed a fatal viral encephalitis. The protective
      effect of the 64TRP vaccine was comparable to that of a single dose of a
      commercial TBEV vaccine, while the transmission-blocking effect of 64TRP was
      better than that of the antiviral vaccine in reducing the number of animals
      supporting virus transmission. By contrast, the commercial antitick vaccine
      (TickGARD) that targets only the tick's midgut showed transmission-blocking
      activity but was not protective. The 64TRP vaccine demonstrates the potential to
      control vector-borne disease by interfering with pathogen transmission,
      apparently by mediating a local cutaneous inflammatory immune response at the
      tick-feeding site.

PMID- 16604155
TI  - On the mechanism of gene amplification induced under stress in Escherichia coli.
AB  - Gene amplification is a collection of processes whereby a DNA segment is
      reiterated to multiple copies per genome. It is important in carcinogenesis and
      resistance to chemotherapeutic agents, and can underlie adaptive evolution via
      increased expression of an amplified gene, evolution of new gene functions, and
      genome evolution. Though first described in the model organism Escherichia coli
      in the early 1960s, only scant information on the mechanism(s) of amplification
      in this system has been obtained, and many models for mechanism(s) were possible.
      More recently, some gene amplifications in E. coli were shown to be stress
      inducible and to confer a selective advantage to cells under stress (adaptive
      amplifications), potentially accelerating evolution specifically when cells are
      poorly adapted to their environment. We focus on stress-induced amplification in
      E. coli and report several findings that indicate a novel molecular mechanism,
      and we suggest that most amplifications might be stress-induced, not spontaneous.
      First, as often hypothesized, but not shown previously, certain proteins used for
      DNA double-strand-break repair and homologous recombination are required for
      amplification. Second, in contrast with previous models in which homologous
      recombination between repeated sequences caused duplications that lead to
      amplification, the amplified DNAs are present in situ as tandem, direct repeats
      of 7-32 kilobases bordered by only 4 to 15 base pairs of G-rich homology,
      indicating an initial non-homologous recombination event. Sequences at the
      rearrangement junctions suggest nonhomologous recombination mechanisms that occur
      via template switching during DNA replication, but unlike previously described
      template switching events, these must occur over long distances. Third, we
      provide evidence that 3'-single-strand DNA ends are intermediates in the process,
      supporting a template-switching mechanism. Fourth, we provide evidence that
      lagging-strand templates are involved. Finally, we propose a novel, long-distance
      template-switching model for the mechanism of adaptive amplification that
      suggests how stress induces the amplifications. We outline its possible
      applicability to amplification in humans and other organisms and circumstances.

PMID- 16604156
TI  - Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis.
AB  - Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome
      characterized primarily by tumors of multiple endocrine glands. The gene for MEN1
      encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was
      recently shown to interact with several components of a trithorax family histone
      methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto
      oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain
      insights into the endocrine-specific tumor phenotype in MEN1, we mapped the
      genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000
      promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of
      chromatin-immunoprecipitation coupled with microarray analysis. We found that
      menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but
      do not always bind together. These data suggest that menin functions as a general
      regulator of transcription. We also found that factor occupancy generally
      correlates with high gene expression but that the loss of menin does not result
      in significant changes in most transcript levels. One exception is the
      developmentally programmed transcription factor, HLXB9, which is overexpressed in
      islets in the absence of menin. Our findings expand the realm of menin-targeted
      genes several hundred-fold beyond that previously described and provide potential
      insights to the endocrine tumor bias observed in MEN1 patients.

PMID- 16604157
TI  - Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in
      mice.
AB  - There is increasing evidence in both plants and animals that epigenetic marks are
      not always cleared between generations. Incomplete erasure at genes associated
      with a measurable phenotype results in unusual patterns of inheritance from one
      generation to the next, termed transgenerational epigenetic inheritance. The
      Agouti viable yellow (A(vy)) allele is the best-studied example of this
      phenomenon in mice. The A(vy) allele is the result of a retrotransposon insertion
      upstream of the Agouti gene. Expression at this locus is controlled by the long
      terminal repeat (LTR) of the retrotransposon, and expression results in a yellow
      coat and correlates with hypomethylation of the LTR. Isogenic mice display
      variable expressivity, resulting in mice with a range of coat colours, from
      yellow through to agouti. Agouti mice have a methylated LTR. The locus displays
      epigenetic inheritance following maternal but not paternal transmission; yellow
      mothers produce more yellow offspring than agouti mothers. We have analysed the
      DNA methylation in mature gametes, zygotes, and blastocysts and found that the
      paternally and maternally inherited alleles are treated differently. The
      paternally inherited allele is demethylated rapidly, and the maternal allele is
      demethylated more slowly, in a manner similar to that of nonimprinted single-copy
      genes. Interestingly, following maternal transmission of the allele, there is no
      DNA methylation in the blastocyst, suggesting that DNA methylation is not the
      inherited mark. We have independent support for this conclusion from studies that
      do not involve direct analysis of DNA methylation. Haplo-insufficiency for Mel18,
      a polycomb group protein, introduces epigenetic inheritance at a paternally
      derived A(vy) allele, and the pedigrees reveal that this occurs after zygotic
      genome activation and, therefore, despite the rapid demethylation of the locus.

PMID- 16604158
TI  - A model for integrating elementary neural functions into delayed-response
      behavior.
AB  - It is well established that various cortical regions can implement a wide array
      of neural processes, yet the mechanisms which integrate these processes into
      behavior-producing, brain-scale activity remain elusive. We propose that an
      important role in this respect might be played by executive structures
      controlling the traffic of information between the cortical regions involved. To
      illustrate this hypothesis, we present a neural network model comprising a set of
      interconnected structures harboring stimulus-related activity (visual
      representation, working memory, and planning), and a group of executive units
      with task-related activity patterns that manage the information flowing between
      them. The resulting dynamics allows the network to perform the dual task of
      either retaining an image during a delay (delayed-matching to sample task), or
      recalling from this image another one that has been associated with it during
      training (delayed-pair association task). The model reproduces behavioral and
      electrophysiological data gathered on the inferior temporal and prefrontal
      cortices of primates performing these same tasks. It also makes predictions on
      how neural activity coding for the recall of the image associated with the sample
      emerges and becomes prospective during the training phase. The network dynamics
      proves to be very stable against perturbations, and it exhibits signs of scale
      invariant organization and cooperativity. The present network represents a
      possible neural implementation for active, top-down, prospective memory retrieval
      in primates. The model suggests that brain activity leading to performance of
      cognitive tasks might be organized in modular fashion, simple neural functions
      becoming integrated into more complex behavior by executive structures harbored
      in prefrontal cortex and/or basal ganglia.

PMID- 16604159
TI  - RAPID FUNCTIONALIZATION AND LOADING OF SOLID SUPPORTS.

PMID- 16604161
TI  - Structures of protonated arginine dimer and bradykinin investigated by density
      functional theory: further support for stable gas-phase salt bridges.
AB  - The gas-phase structures and energetics of both protonated arginine dimer and
      protonated bradykinin were investigated using a combination of molecular
      mechanics with conformational searching to identify candidate low-energy
      structures, and density functional theory for subsequent minimization and energy
      calculations. For protonated arginine dimer, a good correlation (R = 0.88) was
      obtained between the molecular mechanics and EDF1 6-31+G* energies, indicating
      that mechanics with MMFF is suitable for finding low-energy conformers. For this
      ion, the salt-bridge or ion-zwitterion form was found to be 5.7 and 7.2 kcal/mol
      more stable than the simple protonated or ion-molecule form at the EDF1 6-31++G**
      and B3LYP 6-311++G** levels. For bradykinin, the correlation between the
      molecular mechanics and DFT energies was poor (R = 0.28), indicating that many
      low-energy structures are likely passed over in the mechanics conformational
      searching. This result suggests that structures of this larger peptide ion
      obtained using mechanics calculations alone are not necessarily reliable. The
      lowest energy structure of the salt-bridge form of bradykinin is 10.6 kcal/mol
      lower in energy (EDF1) than the lowest energy simple protonated form at the 6
      311G* level. Similarly, the average energy of all salt-bridge structures
      investigated is 13.6 kcal/mol lower than the average of all the protonated forms
      investigated. To the extent that a sufficient number of structures are
      investigated, these results provide some additional support for the salt-bridge
      form of bradykinin in the gas phase.

PMID- 16604162
TI  - Activation of Peptide ions by blackbody radiation: factors that lead to
      dissociation kinetics in the rapid energy exchange limit.
AB  - Unimolecular rate constants for blackbody infrared radiative dissociation (BIRD)
      were calculated for the model protonated peptide (AlaGly)(n) (n = 2-32) using a
      variety of dissociation parameters. Combinations of dissociation threshold
      energies ranging from 0.8 to 1.7 eV and transition entropies corresponding to
      Arrhenius preexponential factors ranging from very "tight" (A(infinity) = 10(9.9)
      s(-1)) to "loose" (A(infinity) = 10(16.8) s(-1)) were selected to represent
      dissociation parameters within the experimental temperature range (300-520 K) and
      kinetic window (k(uni) = 0.001-0.20 s(-1)) typically used in the BIRD experiment.
      Arrhenius parameters were determined from the temperature dependence of these
      values and compared to those in the rapid energy exchange (REX) limit. In this
      limit, the internal energy of a population of ions is given by a Boltzmann
      distribution, and kinetics are the same as those in the traditional high-pressure
      limit. For a dissociation process to be in this limit, the rate of photon
      exchange between an ion and the vacuum chamber walls must be significantly
      greater than the dissociation rate. Kinetics rapidly approach the REX limit
      either as the molecular size or threshold dissociation energy increases or as the
      transition-state entropy or experimental temperature decreases. Under typical
      experimental conditions, peptide ions larger than 1.6 kDa should be in the REX
      limit. Smaller ions may also be in the REX limit depending on the value of the
      threshold dissociation energy and transition-state entropy. Either modeling or
      information about the dissociation mechanism must be known in order to confirm
      REX limit kinetics for these smaller ions. Three principal factors that lead to
      the size dependence of REX limit kinetics are identified. With increasing
      molecular size, rates of radiative absorption and emission increase, internal
      energy distributions become relatively narrower, and the microcanonical
      dissociation rate constants increase more slowly over the energy distribution of
      ions. Guidelines established here should make BIRD an even more reliable method
      to obtain information about dissociation energetics and mechanisms for
      intermediate size molecules.

PMID- 16604163
TI  - Binding Energies of Proton-Bound Dimers of Imidazole and n-Acetylalanine Methyl
      Ester Obtained by Blackbody Infrared Radiative Dissociation.
AB  - The dissociation kinetics of protonated n-acetyl-L-alanine methyl ester dimer
      (AcAlaME(d)), imidazole dimer, and their cross dimer were measured using
      blackbody infrared radiative dissociation (BIRD). Master equation modeling of
      these data was used to extract threshold dissociation energies (E(o)) for the
      dimers. Values of 1.18 +/- 0.06, 1.11 +/- 0.04, and 1.12 +/- 0.08 eV were
      obtained for AcAlaME(d), imidazole dimer, and the cross dimer, respectively.
      Assuming that the reverse activation barrier for dissociation of the ion-molecule
      complex is negligible, the value of E(o) can be compared to the dissociation
      enthalpy (DeltaH(d) degrees ) from HPMS data. The E(o) values obtained for the
      imidazole dimer and the cross dimer are in agreement with HPMS values; the value
      for AcAlaME(d) is somewhat lower. Radiative rate constants used in the master
      equation modeling were determined using transition dipole moments calculated at
      the semiempirical (AM1) level for all dimers and compared to ab initio (RHF/3
      21G*) calculations where possible. To reproduce the experimentally measured
      dissociation rates using master equation modeling, it was necessary to multiply
      semiempirical transition dipole moments by a factor between 2 and 3. Values for
      transition dipole moments from the ab initio calculations could be used for two
      of the dimers but appear to be too low for AcAlaME(d). These results demonstrate
      that BIRD, in combination with master equation modeling, can be used to determine
      threshold dissociation energies for intermediate size ions that are in neither
      the truncated Boltzmann nor the rapid energy exchange limit.

PMID- 16604164
TI  - Nuclear receptor regulation gears up another Notch.
AB  - In this perspective we describe examples of crosstalk between nuclear receptors
      (NRs) and Notch signaling by means of direct functional interactions between
      components of both pathways. This crosstalk may provide eukaryotic organisms with
      molecular mechanisms for the coordination of llong-distance endocrine signals
      with cell-to-cell juxtacrine communication.

PMID- 16604166
TI  - Nuclear receptor corepressors and PPARgamma.
AB  - The nuclear receptor corepressors NCoR and SMRT repress gene transcription by
      recruiting a histone deacetylase complex. Their roles in PPARgamma action have
      been controversial. Recent evidence, however, suggests that NCoR and SMRT repress
      PPARgamma-mediated transcriptional activity on specific promoters in the
      adipocyte. In addition, by repressing PPARgamma action, these corepressors
      inhibit the ability of adipocyte differentiation to proceed. A further
      understanding of corepressor action in the adipocyte will provide insight into
      the balance of forces regulating adipogenesis, insulin sensitivity, and Type 2
      diabetes mellitus.

PMID- 16604167
TI  - Ligand-induced estrogen receptor alpha degradation by the proteasome: new actors?
AB  - In this perspective we consider new aspects of ligand-induced estrogen receptor
      alpha (ERalpha) degradation. What are the possible roles of CSN5/Jab1 and the CSN
      complex in this process? We compare hormone (estrogen) or pure antagonist
      (fulvestrant) induced degradation of ERalpha and review the effects of kinase
      inhibitors and CRM1-dependent nuclear export on ERalpha degradation and
      transcription activation. A model for ERalpha action integrating these new actors
      is proposed and the relation between hormone-induced ERalpha degradation and
      transcription-activation is discussed.

PMID- 16604165
TI  - The NR4A subgroup: immediate early response genes with pleiotropic physiological
      roles.
AB  - The nuclear hormone receptor (NR) superfamily includes the orphan NR4A subgroup,
      comprised of Nur77 (NR4A1), Nurr1 (NR4A2) and NOR-1 (NR4A3). These NRs are
      classified as early response genes, are induced by a diverse range of signals,
      including fatty acids, stress, growth factors, cytokines, peptide hormones,
      phorbol esters, neurotransmitters, and physical stimuli (for example magnetic
      fields, shear stress). The ability to sense and rapidly respond to changes in the
      cellular environment thus appears to be a hallmark of this subfamily. The members
      of the NR4A subgroup are well conserved in the DNA binding domain (approximately
      91-95%) and the C-terminal ligand-binding domain (approximately 60%), but are
      divergent in the N-terminal AB region. These receptors bind as monomers,
      homodimers and heterodimers with RXRs (to mediate retinoid signaling) to
      different permutations of the canonical NR binding motif. The NR4A subgroup
      activates gene expression in a constitutive ligand-independent manner. NR4A
      mediated trans-activation (LBD) involves unusually active N-terminal AF-1 domains
      that mediate coactivator recruitment. Moreover, the NR4A receptors encode
      atypical LBDs and AF-2 domains. For example, the LBDs contain no cavity due to
      bulky hydrophobic residue side chains, and lack the classical coactivator-binding
      cleft constituted by helices 3, 4 and 12. However, a hydrophobic patch exists
      between helices 11 and 12, that encodes a novel cofactor interface that modulates
      transcriptional activity. In line with the pleiotropic physiological stimuli that
      induce the NR4A subgroup, these orphan NRs have been implicated in cell cycle
      regulation (and apoptosis), neurological disease, steroidogenesis, inflammation,
      carcinogenesis and atherogenesis.

PMID- 16604168
TI  - The cell-specific activity of the estrogen receptor alpha may be fine-tuned by
      phosphorylation-induced structural gymnastics.
AB  - The estrogen receptor alpha (ERalpha) regulates the transcription of target genes
      by recruiting coregulator proteins through several domains including the two
      activation functions AF1 and AF2. The contribution of the N-terminally located
      AF1 activity is particularly important in differentiated cells, and for ERalpha
      to integrate inputs from other signaling pathways. However, how the
      phosphorylation of key residues influences AF1 activity has long remained
      mysterious, in part because the naturally disordered AF1 domain has resisted a
      structural characterization. The recent discovery of two coregulators that are
      specific for a phosphorylated form of AF1 suggests that phosphorylation, possibly
      in conjunction with the subsequent binding of these coregulators, may enforce a
      stable structure. The binding of the "pioneer" coregulators might facilitate the
      subsequent recruitment of yet other coregulators. Different AF1 folds may be
      enabled by the combinatorial action of posttranslational modifications and
      coregulator binding thereby fine-tuning ERalpha activities in a cell- and
      promoter-specific fashion.

PMID- 16604169
TI  - Single-step purification of full-length human androgen receptor.
AB  - The full-length human androgen receptor with an N-terminal biotin acceptor
      peptide tag was overexpressed in Spodoptera frugiperda cells in the presence of 1
      microM dihydrotestosterone. Site-specific biotinylation of BAP was achieved in
      vivo by co-expression of E. coli biotin holoenzyme synthetase. The androgen
      receptor was purified by single-step affinity chromatography using Streptavidin
      Mutein Matrix under native conditions. The resultant protein was active, stable,
      95% homogeneous, and we obtained sufficient yield for use in functional and
      structural studies.

PMID- 16604170
TI  - Detection of designer steroids.
AB  - Illicit use of performance-enhancing steroids has proliferated among a wide range
      of professional and amateur athletes. This problem has attracted broad public
      attention and has led the United States Congress to draft legislation that
      proposes frequent testing of athletes. However, current testing protocols are
      inadequate as athletes can evade detection by using novel steroids that are
      unknown to authorities. We have developed a strategy that overcomes this
      limitation by virtue of its ability to detect "designer steroids" without prior
      knowledge of their existence.

PMID- 16604171
TI  - Corepressors: custom tailoring and alterations while you wait.
AB  - A diverse cadre of metazoan transcription factors mediate repression by
      recruiting protein complexes containing the SMRT (silencing mediator of retinoid
      and thyroid hormone receptor) or N-CoR (nuclear receptor corepressor)
      corepressors. SMRT and N-CoR nucleate the assembly of still larger corepressor
      complexes that perform the specific molecular incantations necessary to confer
      transcriptional repression. Although SMRT and N-CoR are paralogs and possess
      similar molecular architectures and mechanistic strategies, they nonetheless
      exhibit distinct molecular and biological properties. It is now clear that the
      functions of both SMRT and N-CoR are further diversified through alternative mRNA
      splicing, yielding a series of corepressor protein variants that participate in
      distinctive transcription factor partnerships and display distinguishable
      repression properties. This review will discuss what is known about the structure
      and actions of SMRT, N-CoR, and their splicing variants, and how alternative
      splicing may allow the functions of these corepressors to be adapted and tailored
      to different cells and to different developmental stages.

PMID- 16604172
TI  - Chaperoning steroid hormone signaling via reversible acetylation.
AB  - Glucocorticoid receptor (GR) and related steroid hormone receptors are ligand
      dependent transcription factors whose regulation is critical for both homeostasis
      and diseases. The structural maturation of the GR has been shown to require the
      Hsp90 molecular chaperone complex. Evidence indicates that Hsp90-dependent
      maturation is critical for GR ligand binding capacity and activity. While the
      role for Hsp90 in GR function is well established, the regulation of this process
      is not well understood. Here we discuss a recent finding that identifies
      reversible protein acetylation controlled by the deacetylase HDAC6 as a novel
      mechanism that regulates Hsp90-dependent GR maturation. We will also speculate on
      the implications of this finding in steroid hormone signaling, oncogenic
      transformation and its potential therapeutic utility.

PMID- 16604173
TI  - Cardiovascular roles of estrogen receptors: insights gained from knockout models.
AB  - The effects of estrogen are mediated through two functionally distinct receptors,
      estrogen receptor alpha (ER- alpha ), and estrogen receptor beta (ER- beta ),
      both of which are expressed in the cardiovascular system. The etiology of
      cardiovascular disease is believed to result in part from the loss of endogenous
      estrogen, indicating that estrogen and its receptors may play important roles in
      the prevention of cardiovascular disease in women.

PMID- 16604174
TI  - Nuclear receptor corepressors.
AB  - The ability of NR LBDs to transfer repression function to a heterologous DNA
      binding domain, and the cross-squelching of repression by untethered LBDs, has
      suggested that repression is mediated by interactions with putative cellular
      corepressor proteins. The yeast-two hybrid screen for protein interactors has
      proven to be the key to the isolation and characterization of corepressors. This
      short review will focus on N-CoR and SMRT.

PMID- 16604175
TI  - The role of SRC-3 in estrogen-dependent vasoprotection during vascular wall
      remodeling postinjury.
AB  - Estrogen receptors are hormone-inducible transcription factors requiring
      coactivators such as members of the SRC/p160 family to modulate the transcription
      of their target genes. This perspective will examine the interplay between
      estrogen receptors and their coactivators in vasoprotection during vascular wall
      remodeling.

PMID- 16604176
TI  - Structural insights into regulation of nuclear receptors by ligands.
AB  - Nuclear receptors are DNA-binding transcription factors, the transcriptional
      function of many of which depends on the binding of ligands, a feature that
      distinguishes nuclear receptors from other transcription factors. This review
      will summarize recent advances in our knowledge of the interaction between
      selected nuclear receptors and their cognate ligands.

PMID- 16604177
TI  - Expression and function profiling of orphan nuclear receptors using bacterial
      artificial chromosome (BAC) transgenesis.
AB  - The long term goal of the Nuclear Receptor Signaling Atlas (NURSA) resides in
      unraveling the physiological and pathological functions of nuclear receptors
      (NRs) at the molecular, biochemical and cellular levels. This multi-oriented task
      requires complementary approaches in order to determine the specific function(s)
      and precise expression and receptor activity patterns for each individual
      conventional or orphan receptor. To attain this objective, we have chose to turn
      to technologies recently made available to engineer bacterial artificial
      chromosomes (BACs).

PMID- 16604178
TI  - PPAR-gamma: a thrifty transcription factor.
AB  - The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a
      prototypical metabolic nuclear receptor that acts as a lipid sensor, integrating
      the homeostatic control of energy, lipid, and glucose metabolism. This
      perspective will highlight three lines of evidence which place PPAR-gamma as a
      key player in a feed-forward pathway favoring differentiation and energy storage
      by adipocytes.

PMID- 16604179
TI  - The varied roles of nuclear receptors during vertebrate embryonic development.
AB  - Nuclear receptors comprise a superfamily of sequence-specific transcription
      factors whose members have diverse roles during development. This review will
      summarize the developmental roles of selected members of the nuclear receptor
      superfamily.

PMID- 16604180
TI  - RNAi technology and its use in studying the function of nuclear receptors and
      coregulators.
AB  - Until just a few years ago, RNA interference (RNAi) technology was restricted to
      the research fields of plants, C. elegans or Drosophila. The discovery of gene
      silencing by in vitro synthesized double-stranded RNA (dsRNA) in mammalian cells
      has made the use of RNAi possible in nearly the entire life science kingdom. DNA
      vectors delivering small interfering RNA (siRNA) directed by polymerase III or
      polymerase II promoters to persistently inhibit target genes expression have
      extended this technology to study in vivo function of these genes. Recently, RNAi
      has been used as a powerful tool in the functional analysis of nuclear receptors
      and their coregulators. This short review will cover studies in this area.

PMID- 16604181
TI  - Therapeutic androgen receptor ligands.
AB  - In the past several years, the concept of tissue-selective nuclear receptor
      ligands has emerged. This concept has come to fruition with estrogens, with the
      successful marketing of drugs such as raloxifene. The discovery of raloxifene and
      other selective estrogen receptor modulators (SERMs) has raised the possibility
      of generating selective compounds for other pathways, including androgens (that
      is, selective androgen receptor modulators, or SARMs).

PMID- 16604182
TI  - Sequentiality and processivity of nuclear receptor coregulators in regulation of
      target gene expression.
AB  - A series of data has accumulated over the past five years that raises questions
      about our current understanding of the transcriptional process and its
      regulation. Following the discovery of coactivators for nuclear receptors (NRs),
      a large number of these molecules have been reported in the literature. This
      perspective will summarize some opinions on the significance of this large number
      of factors.

PMID- 16604184
TI  - Quantitative real-time PCR protocol for analysis of nuclear receptor signaling
      pathways.
AB  - A major goal of the Nuclear Receptor Signaling Atlas (NURSA) is to elucidate the
      biochemical and physiological roles of nuclear receptors in vivo. Characterizing
      the tissue expression pattern of individual receptors and their target genes in
      whole animals under various pharmacological conditions and genotypes is an
      essential component of this aim. Here we describe a high-throughput quantitative,
      real-time, reverse-transcription PCR (QPCR) method for the measurement of both
      the relative level of expression of a particular transcript in a given tissue or
      cell type, and the relative change in expression of a particular transcript after
      pharmacologic or genotypic manipulation. This method is provided as a
      standardized protocol for those in the nuclear receptor field. It is meant to be
      a simplified, easy to use protocol for the rapid, high-throughput measurement of
      transcript levels in a large number of samples. A subsequent report will provide
      validated primer and probe sequence information for the entire mouse and human
      nuclear receptor superfamily.

PMID- 16604183
TI  - Potential roles of ROR-alpha in cardiovascular endocrinology.
AB  - Atherosclerosis is a chronic disease of the arteries whose development involves a
      local inflammatory response characterized by the activation of different cells
      such as macrophages, T-lymphocytes, smooth muscle cells (SMCs) and endothelial
      cells (ECs). This review will summarize recent evidence for a modulatory role of
      the nuclear receptor ROR-alpha in cardiovascular disease.

PMID- 16604185
TI  - Linking lipids, Alzheimer's and LXRs?
AB  - Deposition of the beta-amyloid (Abeta) peptide is thought to underlie development
      of Alzheimer's disease (AD). This pathological linkage has spurred considerable
      interest in therapeutic strategies to reduce Abeta production. It is becoming
      increasingly clear that altered cholesterol homeostasis can modulate Abeta
      production and/or accumulation. In this review, we discuss the molecular
      pathology of AD, the cholesterol connection and recent data suggesting that the
      oxysterol receptor, liver X receptor LXR (NR1H2 and NR1H3), may modulate these
      events.

PMID- 16604186
TI  - Understanding the degradation of hominid gene control.

PMID- 16604187
TI  - Spatiotemporal expression control correlates with intragenic scaffold matrix
      attachment regions (S/MARs) in Arabidopsis thaliana.
AB  - Scaffold/matrix attachment regions (S/MARs) are essential for structural
      organization of the chromatin within the nucleus and serve as anchors of
      chromatin loop domains. A significant fraction of genes in Arabidopsis thaliana
      contains intragenic S/MAR elements and a significant correlation of S/MAR
      presence and overall expression strength has been demonstrated. In this study, we
      undertook a genome scale analysis of expression level and spatiotemporal
      expression differences in correlation with the presence or absence of genic S/MAR
      elements. We demonstrate that genes containing intragenic S/MARs are prone to
      pronounced spatiotemporal expression regulation. This characteristic is found to
      be even more pronounced for transcription factor genes. Our observations
      illustrate the importance of S/MARs in transcriptional regulation and the role of
      chromatin structural characteristics for gene regulation. Our findings open new
      perspectives for the understanding of tissue- and organ-specific regulation of
      gene expression.

PMID- 16604188
TI  - Estimating Costs and Benefits of CTL Escape Mutations in SIV/HIV Infection.
AB  - Mutations that allow SIV/HIV to avoid the cytotoxic T lymphocyte (CTL) response
      are well documented. Recently, there have been a few attempts at estimating the
      costs of CTL escape mutations in terms of the reduction in viral fitness and the
      killing rate at which the CTL response specific to one viral epitope clears virus
      infected cells. Using a mathematical model we show that estimation of both
      parameters depends critically on the underlying changes in the replication rate
      of the virus and the changes in the killing rate over time (which in previous
      studies were assumed to be constant). We provide a theoretical basis for
      estimation of these parameters using in vivo data. In particular, we show that 1)
      by assuming unlimited virus growth one can obtain a minimal estimate of the
      fitness cost of the escape mutation, and 2) by assuming no virus growth during
      the escape, one can obtain a minimal estimate of the average killing rate. We
      also discuss the conditions under which better estimates of the average killing
      rate can be obtained.

PMID- 16604190
TI  - Dynamical principles of two-component genetic oscillators.
AB  - Genetic oscillators based on the interaction of a small set of molecular
      components have been shown to be involved in the regulation of the cell cycle,
      the circadian rhythms, or the response of several signaling pathways. Uncovering
      the functional properties of such oscillators then becomes important for the
      understanding of these cellular processes and for the characterization of
      fundamental properties of more complex clocks. Here, we show how the dynamics of
      a minimal two-component oscillator is drastically affected by its genetic
      implementation. We consider a repressor and activator element combined in a
      simple logical motif. While activation is always exerted at the transcriptional
      level, repression is alternatively operating at the transcriptional (Design I) or
      post-translational (Design II) level. These designs display differences on basic
      oscillatory features and on their behavior with respect to molecular noise or
      entrainment by periodic signals. In particular, Design I induces oscillations
      with large activator amplitudes and arbitrarily small frequencies, and acts as an
      "integrator" of external stimuli, while Design II shows emergence of oscillations
      with finite, and less variable, frequencies and smaller amplitudes, and detects
      better frequency-encoded signals ("resonator"). Similar types of stimulus
      response are observed in neurons, and thus this work enables us to connect very
      different biological contexts. These dynamical principles are relevant for the
      characterization of the physiological roles of simple oscillator motifs, the
      understanding of core machineries of complex clocks, and the bio-engineering of
      synthetic oscillatory circuits.

PMID- 16604191
TI  - Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via
      HSJ1b and transglutaminase.
AB  - There is no treatment for the neurodegenerative disorder Huntington disease (HD).
      Cystamine is a candidate drug; however, the mechanisms by which it operates
      remain unclear. We show here that cystamine increases levels of the heat shock
      DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits
      polyQ-huntingtin-induced death of striatal neurons and neuronal dysfunction in
      Caenorhabditis elegans. This neuroprotective effect involves stimulation of the
      secretory pathway through formation of clathrin-coated vesicles containing brain
      derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from the
      Golgi region that is blocked by reducing HSJ1b levels or by overexpressing
      transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form
      of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain.
      Finally, cysteamine increases serum levels of BDNF in mouse and primate models of
      HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels
      can be used as a biomarker for drug efficacy.

PMID- 16604192
TI  - "Viral deja vu" elicits organ-specific immune disease independent of reactivity
      to self.
AB  - Autoimmune diseases are often precipitated by viral infections. Yet our current
      understanding fails to explain how viruses trigger organ-specific autoimmunity
      despite thymic tolerance extending to many non-lymphohematopoietic self antigens.
      Additionally, a key epidemiological finding needs to be explained: In genetically
      susceptible individuals, early childhood infections seem to predispose them to
      multiple sclerosis (MS) or type 1 diabetes years or even decades before clinical
      onset. In the present work, we show that the innate immune system of neonatal
      mice was sufficient to eliminate an attenuated lymphocytic choriomeningitis virus
      (LCMV) from most tissues except for the CNS, where the virus persisted in neurons
      (predisposing virus). Virus-specific cytotoxic T cells (CTLs) were neither
      deleted nor sufficiently primed to cause disease, but they were efficiently
      triggered in adulthood upon WT LCMV infection (precipitating virus). This defined
      sequence of viral infections caused severe CNS inflammation that was
      histomorphologically reminiscent of rasmussen encephalitis, a fatal human
      autoimmune disease. Yet disease in mice was mediated by antiviral CTLs targeting
      an epitope shared by the precipitating virus and the predisposing virus
      persisting in neurons (deja vu). Thus the concept of "viral deja vu" demonstrates
      how 2 related but independently encountered viral infections can cause organ
      specific immune disease without molecular mimicry of self and without breaking
      self tolerance.

PMID- 16604193
TI  - Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence
      of bradykinin B2 receptors.
AB  - We have previously reported that genetically increased angiotensin-converting
      enzyme levels, or absence of the bradykinin B2 receptor, increase kidney damage
      in diabetic mice. We demonstrate here that this is part of a more general
      phenomenon - diabetes and, to a lesser degree, absence of the B2 receptor,
      independently but also largely additively when combined, enhance senescence
      associated phenotypes in multiple tissues. Thus, at 12 months of age, indicators
      of senescence (alopecia, skin atrophy, kyphosis, osteoporosis, testicular
      atrophy, lipofuscin accumulation in renal proximal tubule and testicular Leydig
      cells, and apoptosis in the testis and intestine) are virtually absent in WT
      mice, detectable in B2 receptor-null mice, clearly apparent in mice diabetic
      because of a dominant mutation (Akita) in the Ins2 gene, and most obvious in
      Akita diabetic plus B2 receptor-null mice. Renal expression of several genes that
      encode proteins associated with senescence and/or apoptosis (TGF-beta1,
      connective tissue growth factor, p53, alpha-synuclein, and forkhead box O1)
      increases in the same progression. Concomitant increases occur in 8-hydroxy-2'
      deoxyguanosine, point mutations and deletions in kidney mitochondrial DNA, and
      thiobarbituric acid-reactive substances in plasma, together with decreases in the
      reduced form of glutathione in erythrocytes. Thus, absence of the bradykinin B2
      receptor increases the oxidative stress, mitochondrial DNA damage, and many
      senescence-associated phenotypes already present in untreated Akita diabetic
      mice.

PMID- 16604195
TI  - Current understanding of delayed anticonvulsant hypersensitivity reactions.
AB  - Hypersensitivity syndrome (HSS) reactions are one of the most feared
      idiosyncratic drug reactions and are most common with exposure to antiepileptic
      drugs (AEDs), sulfonamides, nonsteroidal antiinflammatory drugs, corticosteroids,
      and allopurinol. HSS is associated with chemotoxic and T-cell-mediated
      inflammatory injuries in barrier tissue systems that contain cytochrome oxidases
      (e.g., skin, mucosa, liver, and lungs) and can be seen as a derangement in the
      defense system against xenobiotics-bioactive foreign molecules. The mechanisms
      for anticonvulsant HSS are incompletely understood but involve genetic
      susceptibility, with accumulation of AEDs and oxidized metabolites causing major
      histocompatibility complex (MHC) and non-MHC-dependent clonal activation of T
      cells and subsequent cytokine/chemokine production in T cells, keratinocytes, and
      other target cells. This review discusses the classification and possible
      mechanisms for anticonvulsant HSS.

PMID- 16604196
TI  - Hepatic enzyme induction: it does really matter.

PMID- 16604194
TI  - The human herpesvirus 8 chemokine receptor vGPCR triggers autonomous
      proliferation of endothelial cells.
AB  - We have used a novel conditional transgenic system to study the mechanisms of
      angioproliferation induced by viral G protein-coupled receptor (vGPCR), the
      constitutively active chemokine receptor encoded by human herpesvirus 8 (HHV8,
      also known as Kaposi sarcoma herpesvirus). Using this system, we were able to
      control temporal expression of vGPCR and to monitor its expression in situ via
      the use of the surrogate marker LacZ. Upon treatment with doxycycline (DOX),
      cells expressing vGPCR and LacZ (vGPCR/LacZ(+) cells) progressively accumulated
      in areas where angioproliferation was observed. Sorted vGPCR/LacZ(+) cells from
      angiogenic lesions expressed markers characteristic of endothelial progenitor
      cells, produced angiogenic factors, and proliferated in vitro. Prolonged
      treatment of transgenic mice with DOX led to development of tumors in the skin of
      ears, tail, nose, and paws. vGPCR/LacZ(+) cells were frequent in early lesions
      but scarce within these tumors. Finally, transfer of vGPCR/LacZ(+) cells into
      Rag1(-/-) mice treated with DOX led to angioproliferation and, with time, to
      development of tumors containing both vGPCR/LacZ(+) and vGPCR/LacZ(-) cells.
      Taken together, these results indicate that vGPCR triggers angioproliferation
      directly and suggest a novel role for this molecule in the pathogenesis of Kaposi
      sarcoma.

PMID- 16604198
TI  - Misery across the lifespan.

PMID- 16604197
TI  - Expanding the geography of epilepsy: imaging evidence for Basal Ganglia
      involvement.

PMID- 16604199
TI  - Memory loss after left anterior temporal lobectomy in patients with mesial
      temporal lobe sclerosis.

PMID- 16604200
TI  - A cerebral network reflecting reorganization in medial temporal lobe epilepsy.

PMID- 16604201
TI  - A fishy epilepsy model.

PMID- 16604202
TI  - The multidrug transporter hypothesis of refractory epilepsy: corroboration and
      contradiction in equal measure.

PMID- 16604203
TI  - Kainate receptors "sprout" on epileptic granule cells.

PMID- 16604204
TI  - Activation of Fos during spontaneous hippocampal seizures in a model of temporal
      lobe epilepsy.

PMID- 16604205
TI  - Invulnerability of the immature brain to seizures: do dogmas have nine lives?

PMID- 16604206
TI  - Interception of quorum sensing in Staphylococcus aureus: a new niche for
      peptidomimetics.
AB  - Pathogenesis in Staphylococcus aureus is dependent on local cell density and is
      regulated in part by small macrocyclic peptides. Natural and artificial peptide
      inhibitors of this quorum sensing response have been synthesized and evaluated in
      structure-activity relationship studies. These investigations have illuminated
      the quorum sensing mechanism and set the stage for the design of biostable,
      peptidomimetic inhibitors that could be developed ultimately as therapeutics.

PMID- 16604207
TI  - Microtiter plate based chemistry and in situ screening: a useful approach for
      rapid inhibitor discovery.
AB  - The use of libraries extracted from nature or constructed by combinatorial
      chemistry, have been widely appreciated in the drug discovery area. In this
      perspective, we present our contribution to the field of enzyme inhibitor
      discovery using a useful approach that allows diversification of a common core in
      a microtiter plate followed by in situ screening. Our method relies on an organic
      reaction that is highly selective, high yielding, amenable to the microscale and
      preferably can be performed in water. The core can be a designed molecule based
      on the structural and mechanistic information of the target, a compound with a
      weak binding affinity, or a natural product. Several reactions were found useful
      for this approach and were applied to the rapid discovery of potent inhibitors of
      representative enzymes.

PMID- 16604208
TI  - Substrate specificity in enzymatic fluorination. The fluorinase from Streptomyces
      cattleya accepts 2'-deoxyadenosine substrates.
AB  - The fluorinase enzyme from Streptomyces cattleya displays an unusual ability in
      biocatalysis in that it forms a C-F bond. We now report that the enzyme will
      accept 2'-deoxyadenosine in place of adenosine substrates, and structural
      evidence reveals a reorganisation in hydrogen bonding to accommodate this
      substrate series. It emerges from this study that the enzyme does not require a
      planar ribose conformation of the substrate to catalyse C-F bond formation.

PMID- 16604209
TI  - Solid-phase synthesis of CD40L mimetics.
AB  - The C3-symmetric molecule has been previously shown to mimic CD40 ligand (CD40L)
      homotrimers and to display effector functions. This molecule consists of a cyclic
      hexapeptide core containing the repetition of the D-Ala-L-Lys motif. The side
      chains of the lysine residues have been modified by appending the CD40L-derived
      sequence 143Lys-Gly-Tyr-Tyr146 via a 6-aminohexanoic acid residue as a spacer.
      The present report describes a general solid-phase synthesis approach to and
      related trimeric architectures. In addition, their CD40 binding properties as
      well as their effector functions have been evaluated.

PMID- 16604210
TI  - Tandem radical rearrangement/Pd-catalysed translocation of
      bicyclo[2.2.2]lactones. An efficient access to the oxa-triquinane core structure.
AB  - The skeletal rearrangement of bicyclo[2.2.2]lactones, involving a mild and
      chemoselective palladium-catalysed translocation key-step, provides an efficient
      and diastereoselective access to synthetically useful bicyclo[3.3.0]lactones.

PMID- 16604211
TI  - Traditional Morita-Baylis-Hillman reaction of aldehydes with methyl vinyl ketone
      co-catalyzed by triphenylphosphine and nitrophenol.
AB  - In the Morita-Baylis-Hillman reaction of aldehydes with methyl vinyl ketone
      (MVK), we found that in the presence of a catalytic amount of phenol, the Lewis
      base triphenylphosphine can effectively promote the reaction to give the
      corresponding normal Morita-Baylis-Hillman adducts in good yields. The mechanism
      has been investigated by 31P NMR spectroscopy. The solvent and substituent
      effects were also examined.

PMID- 16604212
TI  - Diastereoselective aldol reactions with butane-2,3-diacetal protected
      glyceraldehyde derivatives.
AB  - Diastereoselective aldol coupling reactions with butane-2,3-diacetal (BDA)
      protected glyceraldehyde derivatives are reported. Good selectivities of up to
      20:1 for the homologated aldol products have been achieved in preparatively
      useful yields.

PMID- 16604213
TI  - Microalga Chlorella sorokiniana: a new sulfoxidation biocatalyst.
AB  - Whole cells of the microalga Chlorella sorokiniana were evaluated in the
      oxidation of prochiral thioethers as regards conversion, enantiomeric excess and
      enantioselectivity.

PMID- 16604214
TI  - Direct, efficient, and inexpensive formation of alpha-hydroxyketones from olefins
      by hydrogen peroxide oxidation catalyzed by the 12-tungstophosphoric
      acid/cetylpyridinium chloride system.
AB  - The direct ketohydroxylation of a variety of 1-aryl-1-alkenes with H2O2,
      catalyzed by the inexpensive 12-tungstophosphoric acid/cetylpyridinium chloride
      system under very mild conditions, was achieved. Various acyloins were obtained
      in good yields and high regioselectivies.

PMID- 16604215
TI  - Two separate and distinct syntheses of stereospecifically deuteriated samples of
      (2S)-proline.
AB  - Two distinct syntheses of samples of the amino acid L-proline which are
      stereospecifically deuteriated on the beta-carbon atom are reported. In the first
      of these, the labelled diazoketones 6, prepared by a chemico-enzymatic synthesis,
      have been photolysed in alkaline conditions to give the corresponding labelled
      methyl pyroglutamates 10 via hydrolysis and intramolecular trapping of the
      resultant ketene intermediates 9. These were then converted into (2S,3S)-[3
      (2)H1]- and (2S,3R)-[2,3-(2)H2]-proline, 1a and 1b respectively. The second
      synthesis provides (2S)-[3,3-(2)H2]-, (2S,3S)- and (2S,3R)-[3-(2)H1]-proline, 1d,
      1a and 1c respectively, and has as its key step the highly stereoselective
      hydrolysis of the silylenol ethers 14 and 14a respectively in which deuteriation
      or protonation occurs from the re-face of the enol ether.

PMID- 16604216
TI  - Synthesis of (2S,3S)-[3-(2)H1]-4-methyleneglutamic acid and (2S,3R)-[2,3-(2)H2]-4
      methyleneglutamic acid.
AB  - (2S,3S)-[3-(2)H1]-4-Methyleneglutamic acid 1a and (2S,3R)-[2,3-(2)H2]-4
      methyleneglutamic acid 1b have been synthesised for use in biosynthetic and
      metabolic studies.

PMID- 16604217
TI  - Clickity-click: highly functionalized peptoid oligomers generated by sequential
      conjugation reactions on solid-phase support.
AB  - N-Substituted glycine peptoid oligomers were used as substrates for azide-alkyne
      [3 + 2] cycloaddition conjugation reactions and then elaborated through
      additional rounds of oligomerization and cycloaddition. This novel sequential
      conjugation technique allowed for the generation of complex peptidomimetic
      products in which multiple heterogeneous pendant groups were site-specifically
      positioned along the oligomer scaffold. Studies of a water-soluble estradiol
      ferrocene peptoid conjugate demonstrated a potential application for the modular
      synthesis of biosensors.

PMID- 16604218
TI  - Molecular fluorescent pH-probes based on 8-hydroxyquinoline.
AB  - Three 5,7-pi-extended 8-benzyloxyquinolines, namely 5,7-diphenyl-, 5,7
      bis(biphenyl-4-yl)- and 5,7-bis(4-dibenzothiophenyl)-8-benzyloxyquinoline were
      prepared and investigated as fluorescent pH-probes in nonaqueous solution.
      Absorption and photoluminescence spectra of the introduced compounds also
      including the starting material 8-benzyloxy-5,7-dibromoquinoline as well as their
      N-protonated counterparts were recorded and the results were rationalized by
      quantum-chemical calculations. A pronounced red shift of the emission occurred
      upon protonation of the non halogenated derivatives, while the dibromo-derivative
      is hardly emissive and is virtually not protonated under the conditions used. The
      diphenyl- and the bis(biphenyl)-derivative especially show promising
      photoluminescence quantum yields both in the parent and the protonated state
      making them candidates for the active component in pH sensing applications.

PMID- 16604219
TI  - Quinolactacins revisited: from lactams to imide and beyond.
AB  - Chemical analysis of a solid phase fermentation of an Australian Penicillium
      citrinum strain has returned all known examples of a rare class of N-methyl
      quinolone lactams, quinolactacins A2 (1), B2 (2), C2 (3) and A1 (4), together
      with the new quinolactacins B1 (5), C1 (6), D1 (7) and D2 (8), and the novel
      derivatives quinolonimide (9) and quinolonic acid (10). Complete stereostructures
      were assigned to all these compounds by detailed spectroscopic analysis and
      chemical interconversion. Carefully controlled and monitored decomposition
      studies have confirmed that quinolactacins readily undergo C-3 epimerization and
      oxidation, and under appropriate conditions convert to quinolonimide and
      quinolonic acid. Mechanisms for key transformations are proposed. The
      decomposition studies suggested that only quinolactacins A2 (1) and B2 (2) are
      genuine natural products, with all other isolated compounds being decomposition
      artefacts. Quinolactacins C1 (6), C2 (3), and the racemic mixture of
      quinolactacins D1/D2 (8/7) all displayed notable cytotoxic activity.

PMID- 16604220
TI  - Citrinin revisited: from monomers to dimers and beyond.
AB  - Detailed chemical analysis of the solid phase fermentation of an Australian
      Penicillium citrinum isolate has returned the known compounds citrinin (1),
      phenol A acid (6), dihydrocitrinone (7) and dihydrocitrinin (8), together with a
      novel cytotoxic dimer, dicitrinin A (5). Dicitrinin A (5) was determined to be a
      dimerised artefact of the major co-metabolite citrinin, and its structure solved
      by spectroscopic analysis and chemical modification. Analysis of the products
      encountered during the controlled decomposition of citrinin led to the discovery
      of additional citrinin dimers and delineated a plausible mechanistic pathway
      linking all monomeric and dimeric citrinin degradation products.

PMID- 16604221
TI  - Anion-templated assembly of [2]rotaxanes.
AB  - Anion templation is used to develop a general method for rotaxane synthesis. The
      anion-templated synthesis of three new [2]rotaxanes containing positively charged
      pyridinium axles and neutral isophthalamide macrocyclic components is described.
      The incorporation of electron withdrawing substituents, such as the nitro group,
      into the 5-position of an isophthalamide bis-vinyl acyclic precursor results in a
      significant improvement in [2]rotaxane assembly yields. Rotaxane anion binding
      strengths are also enhanced whilst the rotaxane's unique interlocked binding
      domain ensures selectivity for chloride--the templating anion--is maintained.

PMID- 16604222
TI  - The influence of hydrogen bonding and pi-pi stacking interactions on the self
      assembly properties of C3-symmetrical oligo(p-phenylenevinylene) discs.
AB  - Three C3-symmetrical discotics containing a 1,3,5-benzenetricarboxamide unit
      functionalized with pi-conjugated oligo(p-phenylenevinylene)s (OPV)s have been
      synthesized and fully characterized. For the two amide OPV discs a two-step
      transition from helical stacks to molecularly dissolved species was observed and
      surprisingly, the topology of the amide determines the stability and helicity of
      the fibers in solution and the length of the fibrils at a surface. In case of the
      bipyridine disc, aggregates were formed that show little chiral ordering while
      the stacks remain present over a large temperature range. At a surface,
      completely disordered structures exist probably as a result of competing types of
      pi-pi stacking interactions that differ in strength and orientation. The results
      show that the design of functional self-assembled architectures based on hydrogen
      bonding and pi-pi stacking interactions is an extremely delicate matter and
      reveal that special demands have to be taken into account to balance the
      topology, directionality and strength of multiple secondary interactions.

PMID- 16604223
TI  - Novel retinylidene iminium salts for defining opsin shifts: synthesis and
      intrinsic chromophoric properties.
AB  - Retinal Schiff bases serve as chromophores in many photoactive proteins that
      carry out functions such as signalling and light-induced ion translocation. The
      retinal Schiff base can be found as neutral or protonated, as all-trans, 11-cis
      or 13-cis isomers and can adopt different conformations in the protein binding
      pocket. Here we present the synthesis and characterisation of isomeric
      retinylidene iminium salts as mimics blocked towards isomerisation at the C11
      position and conformationally restrained. The intrinsic chromophoric properties
      are elucidated by gas phase absorption studies. These studies reveal a small blue
      shift in the S0-->S1 absorption for the 11-locked derivative as compared to the
      unlocked one. The gas phase absorption spectra of all the cationic mimics so far
      investigated show almost no absorption in the blue region. This observation
      stresses the importance of protein interactions for colour tuning, which allows
      the human eye to perceive blue light.

PMID- 16604224
TI  - Substituent control of potassium and rubidium uptake by asymmetric calix[4]
      thiacalix[4]tubes.
AB  - Herein we report on the synthesis and ionophore properties of the first
      asymmetric p-tert-butylcalix[4]-p-R-thiacalix[4]tubes 7a-c (R = t-Bu, H, 1
      adamantyl). The target compounds were obtained by the condensation of
      tosyloxyethoxy-p-tert-butylcalix[4]arene with the corresponding p-R
      thiacalix[4]arenes in the presence of K2CO3 in acetonitrile. The complexation
      with sodium, potassium and rubidium iodides was studied in CDCl3-CD3OD (4:1)
      medium by means of 1H NMR measurements. It was found that the ionophore
      properties of calixtubes 7a-c are controlled by the character of the substituents
      at the upper rim of the thiacalix[4]arene fragment and it was shown that only the
      molecular tube 7c with an adamantane-containing thiacalixarene unit is capable of
      quantitatively binding potassium (swiftly) and rubidium (slowly) cations.

PMID- 16604225
TI  - Asymmetric induction during electron transfer mediated photoreduction of carbonyl
      compounds: role of zeolites.
AB  - Photochemistry of 17 aryl alkyl ketones included within cation exchanged zeolites
      has been examined. In solution five of the 17 ketones undergo intramolecular
      hydrogen abstraction reaction even in the presence of a chiral amine and the rest
      are photoreduced to the corresponding alcohol. Within zeolites all 17 ketones
      yielded in presence of a chiral amine, the corresponding alcohol as the major
      product. When a chiral amine was used as the coadsorbent within alkali ion
      exchanged zeolites, enantiomerically enriched alcohol was formed in all cases.
      The best chiral induction was obtained with phenyl cyclohexyl ketone
      (enantiomeric excess: 68%). 1H-13C Cross Polarization Magic Angle Spinning (CP
      MAS) experiments, with a model ketone (perdeuterated acetophenone) and chiral
      amine (pseudoephedrine) included within MY zeolites, suggested that the cation
      brings the reactant and the chiral amine closer. The role of the cation in such a
      process is also revealed by the computation results. The results presented here
      highlight the importance of a supramolecular structure in forcing a closer
      interaction between a reactant and a chiral inductor that could be used to
      achieve asymmetric induction in photoproducts.

PMID- 16604226
TI  - Synthesis and characterisation of bis-cyclen based dinuclear lanthanide
      complexes.
AB  - The design and synthesis of several bis-macrocyclic cyclen (1,4,7,10
      tetraazacyclododecane) ligands and their corresponding lanthanum or europium
      complexes is described; these dinuclear lanthanide systems were made by
      connecting two macrocyclic cyclen moieties through a rigid, covalent, p
      xylylenediamide bridge or a flexible aliphatic hexane bridge. These ligands were
      subsequently functionalised with six acetamide pendant arms (CONR1R2: R1 = R2 = H
      or CH3, or R1 = H, R2 = CH3). The corresponding lanthanide bis-complexes were
      then formed by reaction with La(III) and Eu(III) triflates, yielding overall
      cationic (+VI charged) complexes.

PMID- 16604227
TI  - Rate and product studies in the solvolyses of N,N-dimethylsulfamoyl and 2
      propanesulfonyl chlorides.
AB  - Contrary to earlier suggestions of an S(N)1 pathway for solvolyses of N,N
      dimethylsulfamoyl chloride (1), an extended Grunwald-Winstein equation treatment
      of the specific rates of solvolysis in 32 solvents shows an appreciable
      sensitivity towards changes in both solvent nucleophilicity and solvent ionizing
      power. The actual values are very similar to those obtained in earlier studies of
      the solvolyses of sulfonyl and phosphoryl chlorides, solvolyses which are
      believed to proceed by an S(N)2 pathway. The observation of similar selectivities
      in aqueous-alcohol solvents further supports this assignment. In a recent report,
      an addition-elimination (association-dissociation) pathway was proposed for
      solvolyses of 2-propanesulfonyl chloride (2). A severe multicollinearity problem
      has been removed by the addition of several specific rates of solvolysis in
      fluoroalcohol-containing solvents. The new analyses using the extended Grunwald
      Winstein equation lead to sensitivities similar to those for and the previously
      studied related compounds, and these solvolyses are also best described as
      following an S(N)2 pathway.

PMID- 16604229
TI  - Investigation of a route to ibotenic acid analogues via a reduced pyroglutamate
      template.
AB  - Two alternative "ring switch" based syntheses have been shown to give access to
      the reduced protected homochiral analogues, 27, 28 and 36, of the CNS active
      compound ibotenic acid.

PMID- 16604228
TI  - A new route to trans-2,6-disubstituted piperidine-related alkaloids using a novel
      C2-symmetric 2,6-diallylpiperidine carboxylic acid methyl ester.
AB  - A novel C2-symmetric 2,6-diallylpiperidine carboxylic acid methyl ester 1 was
      prepared by the double asymmetric allylboration of glutaldehyde followed by an
      aminocyclization and carbamation. On the basis of desymmetrization of 1 using
      iodocarbamation, one allyl group of 1 was protected and monofunctionalizations of
      the resulting oxazolidinone 11 were performed. The reaction of the N
      methoxycarbonyl piperidine 25 employing decarbamation reagent (n-PrSLi or TMSI)
      as a key step gave oxazolidinone 26 or 17 including an intramolecular ring
      formation, which was transformed in a few steps into (-)-porantheridine (2) and (
      )-2-epi-porantheridine (3), respectively. In addition, the expedient synthesis of
      (+)-epi-dihydropinidine (4), (2R,6R)-trans-solenopsin A (5), and precoccinelline
      (6), starting from 11 is described.

PMID- 16604232
TI  - Re-construction and updating our understanding on the global weapons tests 137Cs
      fallout.
AB  - Global nuclear weapons tests fallout of 137Cs in the northern hemisphere has been
      documented in the UNSCEAR (United Nations Scientific Committee on the Effect of
      Atomic Radiation) reports. However, many questions have arisen during the past
      three to four decades; e.g. the water column inventory of 137Cs in the North
      Pacific Ocean was two to three time higher than the cumulative decay corrected
      fallout at the same latitude as stated in the UNSCEAR reports. Here we show more
      precise spatial distribution of global 137Cs fallout primarily on the basis of
      global measurements in rain, seawater and soil, as data from 10 degrees x 10
      degrees grids. A typical feature of geographical distribution is that two high
      global 137Cs fallout areas exist in the northern hemisphere, where the highest
      137Cs fallout was observed in the globe. These areas correspond to crossovers of
      areas where larger precipitation amounts were expected and where higher
      stratosphere-troposphere exchange was expected. Our new estimate of 765 +/- 79
      PBq as global 137Cs fallout for the northern hemisphere is 1.4 times higher than
      that of 545 PBq in the UNSCEAR reports.

PMID- 16604230
TI  - Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of
      CYP3A4.
AB  - A number of furanocoumarins isolated from grapefruit juice have been found to
      inhibit CYP3A4 activity in vitro. In this study, we have designed and synthesised
      a range of analogues based on bergamottin to investigate the relationship between
      chemical structure and inhibition of CYP3A4 activity. Studies were performed
      using human liver microsomes and human intestinal S9 fraction, with testosterone
      as the marker substrate. With the exception of the coumarin and phenolic
      furanocoumarin derivatives, which were inactive, the alkyloxy-furanocoumarin
      analogues were found to inhibit CYP3A4 activity in a dose dependent manner, with
      observed IC50 values ranging from 0.13 +/- 0.03 to 49.3 +/- 1.9 microM. The
      unsaturated furan derivatives were found to exhibit time-dependent inhibition,
      showing a 2-, 4- and 14-fold increase in potency for 6',7'-epoxybergamottin,
      6',7'-dihydroxybergamottin and bergamottin, respectively after a preincubation
      period of ten minutes. Reduction of the furan moiety resulted in an 11-fold
      decrease in inhibitory potency, suggesting that this functional group is key to
      the interaction between these compounds and CYP3A4.

PMID- 16604233
TI  - Sequential element extraction of soils from abandoned farms: an investigation of
      the partitioning of anthropogenic element inputs from historic land use.
AB  - Enhanced soil element concentrations may serve as indicators not only of modern
      pollution, but also of former historic and/or pre-historic human activity.
      However, there is little consensus over the most appropriate means of extraction
      for identifying chemical signatures of modern and archaeological pollution. This
      study addressed this question by using a 5-step sequential extraction to examine
      the partitioning of elements within the soil. Samples were taken from known
      functional areas (hearth, house, byre, arable, and grazing areas) on a 19th
      century abandoned croft (small farm). A hot nitric acid digest and five-stage
      sequential extraction method were used to examine the partitioning of elements in
      soil and identify the current elemental distribution of anthropogenic
      contamination. The results indicate that although a significant proportion of Ca
      tends to be bound with exchangeable and weak acid soluble fractions, in the
      hearth and house areas there is also a significant proportion held within the
      recalcitrant residue. Pb concentrations tend to be associated with organic
      matter, ammonium oxalate extractable fractions and the residue, whilst Zn
      generally has a more even partitioning between the six soil fractions. The
      implications of this for extraction methodology are element and soil specific.
      However, the presence of a significant proportion of anthropogenically
      significant elements (including Ca, Pb, Zn, Sr, and Ba) within the resistant
      residue suggests the use of only a weak acid or an exchangeable fraction
      extraction would result in the loss of information from contamination resulting
      from former human activity. Hence, a total or pseudo-total extraction method is
      recommended for this type of study.

PMID- 16604234
TI  - The assessment of biomarkers in sentinel cattle for monitoring vanadium exposure.
AB  - Various potential biomarkers were sampled for vanadium every 3-4 months from Bos
      indicus beef cattle farmed extensively immediately adjacent (high exposure (HE)
      group) and two km away (low exposure (LE) group) from a vanadium processing
      plant, respectively. Vanadium intake (mg vanadium kg(-1) bwt d(-1)) was modelled
      using environmental and physiological data as inputs. The vanadium intake ranged
      from 0.57 to 5.44 mg vanadium kg(-1) bwt d(-1) in the HE group and 0.41 to 2.61
      mg vanadium kg(-1) bwt d(-1) in the LE group over a five-year period of
      monitoring. Samples collected from live sentinel animals over the five-year
      period included caudal coccygeal vertebrae, tail-switch hair, milk, urine,
      faeces, rib-bone biopsies and a wide range of blood clinical pathology and
      haematological parameters. The data was analysed for differences in response
      between the HE and LE groups. Where differences were found, a linear mixed
      effects regression model was fitted to model the relationship between the
      exposure dose and the response variable. The model included the effects of age,
      duration of exposure and response, and allowed the prediction of the exposure
      dose given these inputs. Moreover, forty-two adult cattle were slaughtered over
      the five years. A wide range of tissue samples, rumen content and whole blood
      were taken from the cattle at slaughter for vanadium determination. In live
      animals, a difference in response was found between the HE group and LE group
      with respect to serum albumin (n = 36), monocyte (n = 36) and thrombocyte (n =
      36) counts, and hair (n = 2) and faeces (n = 34) vanadium concentrations. No
      difference in vanadium concentrations could be shown for urine (n = 36), the
      traditional occupational health biomarker. Regression models are described for
      serum albumin, monocyte counts, faeces and hair, which showed the most promise as
      biomarkers. Average concentrations of vanadium in the tissues of slaughtered
      cattle ranged from 0.08 to 2.94 mg kg(-1) (wet-weight basis) and rumen content
      contained 16.67 mg kg(-1). Significant correlations were found between the
      exposure dose (end-dose) just prior to slaughter and the concentrations of
      vanadium in the coccygeal vertebrae, liver, diaphragm and rib-bone in descending
      order of magnitude. Other tissues showed poor correlation to the end-dose. Tissue
      levels of vanadium in healthy cattle include a much wider range than is currently
      reflected in the literature. The best tissue from slaughter animals for assessing
      chronic vanadium exposure is probably the liver.

PMID- 16604235
TI  - Passive sampling of herbicides combined with effect analysis in algae using a
      novel high-throughput phytotoxicity assay (Maxi-Imaging-PAM).
AB  - We propose to combine a passive sampler for polar organic compounds (POS) with a
      specific bioassay for phytotoxicity to assess the hazard of herbicidal compounds
      in surface waters. The POS consisted of an Empore disk coated with
      styrenedivinylbenzene deployed in a Teflon housing, which has relatively high
      sampling rates (e.g., approximately 1 L d(-1) for diuron). POS were deployed for
      5 days in a small-scale field study in South East Queensland, Australia, in a
      relatively pristine environment and an urban environment to explore sensitivity
      towards herbicides and potential influences of non-herbicidal pollutants. Besides
      chemical analysis of 8 herbicides, a novel bioassay (Maxi-Imaging-PAM, IPAM) was
      employed to assess the phytotoxic effects of water samples and POS extracts. The
      IPAM allows rapid assessment of photosynthetic quantum yields of a large number
      of samples via chlorophyll-fluorescence imaging and the saturation pulse method.
      Sampling rates for several herbicides from laboratory calibrations were found to
      be applicable under field conditions. Toxic equivalent concentrations (with
      reference to the herbicide diuron) were computed from the concentrations
      determined by chemical analysis and the relative potency (also termed toxic
      equivalence factor) of the detected herbicides. There was good agreement between
      diuron equivalent concentrations from chemical analysis and diuron equivalent
      concentrations determined with the IPAM.

PMID- 16604236
TI  - A comparison of European and North American atmospheric deposition networks:
      polycyclic aromatic hydrocarbons and lindane.
AB  - A comparison between the sampling and analytical methods used by Canadian (IADN)
      and German (OSPAR) regional monitoring networks for persistent organic pollutants
      was conducted from September 2002 to October 2003 at a rural site in Ontario,
      Canada. Polycyclic aromatic hydrocarbons (PAHs) and the currently-used pesticide
      lindane were measured in precipitation and ambient air samples. Overall the two
      networks sampling and analytical methods agreed well in their results of
      deposition (wet and dry particulate). Lindane concentrations between the two
      networks agreed well in the air samples while too few precipitation samples could
      be compared to conclude on agreement. The lindane seasonal profile with a peak in
      spring-early summer was consistent with previous results pointing to the
      continued use of this pesticide in 2002-2003 in Canada. Annual lindane wet
      depositions were comparable between the two network methodologies. PAHs
      concentrations in precipitation and in gas phase agreed well while there was a
      discrepancy for particulate PAHs in air. This study confirmed that the use of
      data from the two regional POPs monitoring networks for hemispherical modelling
      studies is warranted.

PMID- 16604237
TI  - Chemical markers of human waste contamination: analysis of urobilin and
      pharmaceuticals in source waters.
AB  - Giving public water authorities another tool to monitor and measure levels of
      human waste contamination of waters simply and rapidly would enhance public
      protection. Most of the methods used today detect such contamination by
      quantifying microbes occurring in feces in high enough densities that they can be
      measured easily. However, most of these microbes, for example E. coli, do not
      serve as specific markers for any one host species and many can have origins
      other than feces. As an alternative, chemicals shed in feces and urine might be
      used to detect human waste contamination of environmental waters. One potential
      chemical marker of human waste is the compound urobilin. Urobilin is one of the
      final by-products of hemoglobin breakdown. Urobilin is excreted in both the urine
      and feces from many mammals, particularly humans. Source waters from 21 sites in
      New England, Nevada, and Michigan were extracted using hydrophilic-lipophilic
      balance (HLB) cartridges and then analyzed by high performance liquid
      chromatography-electrospray mass spectrometry (HPLC-ES-MS). As a marker of human
      waste, urobilin was detected in many of the source waters at concentrations
      ranging from not detectable to 300 ng L(-1). Besides urobilin, azithromycin, an
      antibiotic widely prescribed for human use only in the US, was also detected in
      many of these waters, with concentrations ranging from not detectable to 77 ng L(
      1). This methodology, using both urobilin and azithromycin (or any other human
      use pharmaceutical) could be used to give public water authorities a definitive
      method for tracing the sources of human waste contamination. The analysis and
      detection of urobilin in surface waters by HPLC-ES-MS has not been previously
      reported in the peer-reviewed literature.

PMID- 16604238
TI  - Local and regional air pollution in Ireland during an intensive aerosol
      measurement campaign.
AB  - An intensive two month measurement campaign has been performed during a two year
      study of major component composition of urban PM10 and PM2.5 in Ireland (J. Yin,
      A. G. Allen, R. M. Harrison, S. G. Jennings, E. Wright, M. Fitzpatrick, T. Healy,
      E. Barry, D. Ceburnis and D. McCusker, Atmos. Res., 2005, 78(3-4), 149-165).
      Measurements included size-segregated mass, soluble ions, elemental carbon (EC)
      distributions, fine and coarse fraction organic carbon (OC) and major gases along
      with standard meteorological measurements. The study revealed that urban
      emissions in Ireland had mainly a local character and therefore were confined
      within a limited area of 20-30 km radius, without significantly affecting
      regional air quality. Gaseous measurements have shown that urban emissions in
      Ireland had clear, but fairly limited influence on the regional air quality due
      to favorable mixing conditions at higher wind speeds, in particular from the
      western sector. Size-segregated mass and chemical measurements revealed a clear
      demarcation size between accumulation and coarse modes at about 0.8 microm which
      was constant at all sites. Carbonaceous compounds at the urban site accounted for
      up to 90% of the particle mass in a size range of 0.066-0.61 microm. Nss SO4(2-)
      concentrations in PM2.5 were only slightly higher at the urban site compared to
      the rural or coastal sites, while NO3- and NH4+ concentrations were similar at
      the urban and coastal sites, but were a factor of 2 to 3 higher than at the rural
      site. OC was highly variable between the sites and revealed clear seasonal
      differences. Natural or biogenic OC component accounted for <10% in winter and up
      to 30% in summer of the PM2.5 OC at urban sites. A contribution of biogenic OC
      component to PM2.5 OC mass at rural site was dominant.

PMID- 16604239
TI  - Comparison of pressurized fluid extraction, Soxhlet extraction and sonication for
      the determination of polycyclic aromatic hydrocarbons in urban air and diesel
      exhaust particulate matter.
AB  - In order to characterize and compare the chemical composition of diesel
      particulate matter and ambient air samples collected on filters, different
      extraction procedures were tested and their extraction efficiencies and
      recoveries determined. This study is an evaluation of extraction methods using
      the standard 16 EPA PAHs with HPLC fluorescence analysis. Including LC analysis
      also GC and MS methods for the determination of PAHs can be used. Soxhlet
      extraction was compared with ultrasonic agitation and pressurized fluid
      extraction (PFE) using three solvents to extract PAHs from diesel exhaust and
      urban air particulates. The selected PAH compounds of soluble organic fractions
      were analyzed by HPLC with a multiple wavelength shift fluorescence detector. The
      EPA standard mixture of 16 PAH compounds was used as a standard to identify and
      quantify diesel exhaust-derived PAHs. The most effective extraction method of
      those tested was pressurized fluid extraction using dichloromethane as a solvent.

PMID- 16604240
TI  - Salmonella-based plague vaccines for bioterrorism.
AB  - Yersinia pestis, the causative agent of plague, is an emerging threat as a means
      of bioterrorism. Accordingly, the Working Group on Civilian Biodefense, as well
      as the Centers for Disease Control and Prevention, has specified Y. pestis as a
      prime candidate for use in bioterrorism. As the threat of bioterrorism increases,
      so does the need for an effective vaccine against this potential agent. Experts
      agree that a stable, non-invasive vaccine would be necessary for the rapid large
      scale immunization of a population following a bioterrorism attack. Thus far,
      live Salmonella-based oral vaccines show the most potential for this purpose.
      When delivered via a mucosal route, Salmonella-based plague vaccines show the
      ability to protect against the deadly pneumonic form of plague. Also, mass
      production, distribution, and administration are easier and less costly for
      attenuated Salmonella-based plague vaccines than for plague vaccines consisting
      of purified proteins. Most attenuated Salmonella-based plague vaccines have
      utilized a plasmid-based expression system to deliver plague antigen(s) to the
      mucosa. However, these systems are frequently associated with plasmid
      instability, an increased metabolic burden upon the vaccine strain, and highly
      undesirable antibiotic resistance genes. The future of Salmonella-based plague
      vaccines seems to lie in the use of chromosomally encoded plague antigens and the
      use of in vivo inducible promoters to drive their expression. This method of
      vaccine development has been proven to greatly increase the retention of foreign
      genes, and also eliminates the need for antibiotic resistance genes within
      Salmonella-based vaccines.

PMID- 16604241
TI  - Mycelium and polysaccharide production of Agaricus blazei Murrill by submerged
      fermentation.
AB  - BACKGROUND AND PURPOSE: Over the last decade, Agaricus blazei Murrill has been
      studied and developed as a novel functional food in Japan, Korea, China, and
      Taiwan. Due to the low yields, the fruiting bodies of A. blazei Murrill are
      relatively expensive, and a cheap and stable source of A. blazei Murrill mycelium
      for commercial purposes is highly desirable. Culture media and conditions were
      investigated with a view to reducing the cost and improving the mycelium and
      polysaccharide production of A. blazei Murrill by submerged fermentation.
      METHODS: Thirty six isolates of A. blazei Murrill were isolated from 22 fruiting
      bodies produced in Taiwan, and 16 of them could be successfully cultivated on
      mannitol-egg yolk-polymyxin medium. The isolates were identified by species
      specific polymerase chain reaction (PCR) and optimized for the culture media and
      conditions by submerged fermentation for mycelium and polysaccharide production.
      Some properties of polysaccharide extract were also investigated. RESULTS: All of
      the PCR products with species-specific primers showed high identity and matched
      the internal transcribed spacer 1 sequences of A. blazei Murrill. The phylogenic
      tree of A. blazei Murrill isolates generated from random amplified polymorphic
      DNAs arranged all samples into 3 groups and 2 independent cases. The optimal
      culture media of mycelium production in submerged fermentation were 5% malt
      extract, 0.1% yeast extract, and 0.5% peptone at pH 6.0, while the optimal
      culture conditions were 200 mL medium in 500 mL Hinton flask, shaking at 90 rpm
      for 3 days and then shifting to 105 rpm for 5 days at 27 degrees C. Each liter of
      A. blazei Murrill M72 yielded 10.83 +/- 0.24 g dried mycelia weight and each
      liter of A. blazei Murrill M152 produced 0.251 +/- 0.004 g crude polysaccharide
      (3.03 +/- 0.05% of dried mycelia weight). Crude polysaccharide of A. blazei
      Murrill M162 contained 82.27-99.14% of total sugar and less than 1.63% of
      protein; it had 4 major molecular weight components (274.1, 32.7, 7.5, and 2.1
      kDa, respectively), with the 2.1 kDa portion possibly a beta-(1,3)-glucan.
      CONCLUSIONS: These results show that selection of media and conditions can be
      employed in order to improve the mycelium and polysaccharide production of A.
      blazei Murrill M72 or M152 by submerged fermentation. Mycelia and polysaccharide
      production of A. blazei Murrill with submerged fermentation is potentially
      feasible.

PMID- 16604242
TI  - Levels of intracellular adhesion molecule-1 and vascular cell adhesion molecule-1
      in children with Henoch-Schonlein purpura.
AB  - BACKGROUND AND PURPOSE: Henoch-Schonlein purpura (HSP) is a small vessel
      vasculitis. Soluble adhesion molecules play a very important role in the immuno
      inflammatory reaction of damaged vascular tissues. This study investigated the
      prognostic and diagnostic potential of soluble intracellular adhesion molecule-1
      (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in HSP. METHODS: Serum
      levels of sICAM-1 and sVCAM-1 were studied in 26 children with HSP. Paired blood
      samples (during acute and convalescent stages) were collected from 17 of the
      children and assayed by enzyme-linked immunosorbent assay. Correlations with
      clinical manifestations were examined. Seventeen healthy children served as
      controls. RESULTS: Both sICAM-1 and sVCAM-1 were significantly elevated at the
      acute stage compared with the remission stage of HSP patients versus controls
      (p=0.006 and p=0.0173, respectively). CONCLUSIONS: Although the levels of sICAM-1
      and sVCAM-1 were not correlated with the severity of clinical manifestations in
      HSP, these soluble adhesion molecules may serve as diagnostic markers.

PMID- 16604243
TI  - Effect of regular intravenous immunoglobulin therapy on prevention of pneumonia
      in patients with common variable immunodeficiency.
AB  - BACKGROUND AND PURPOSE: Common variable immunodeficiency (CVID) is a primary
      immunodeficiency disorder, which presents with hypogammaglobulinemia and
      recurrent bacterial infections. Patients with CVID have frequent and severe
      episodes of pneumonia. The standard intravenous immunoglobulins (IVIG) therapy
      has led to the reduction of pulmonary infections in these patients. The aim of
      this study was to evaluate the effectiveness of IVIG treatment in reducing the
      incidence of pneumonia in patients with CVID. METHODS: Twenty six Iranian
      patients with CVID whose diseases had been diagnosed at the Children Medical
      Center and had received regular IVIG for at least 9 months were selected. The
      numbers of episodes of pneumonia and hospital admissions were documented before
      and during treatment with IVIG. RESULTS: Of 26 patients with CVID, 80.5% had
      experienced pneumonia at least once before receiving immunoglobulin and 88.5%
      required hospital admission. After starting treatment with IVIG (mean treatment
      period, 41.5 +/- 35.4 months), the annual incidence of pneumonia significantly
      decreased from 80.5% to 34.6% (p=0.0017), and the rate of hospitalization from
      88.5% to 46% (p=0.0025) . The incidence of pneumonia requiring treatment or
      hospitalization fell from 3.4 to 0.7 per year (p<0.0005). CONCLUSIONS: Regular
      IVIG therapy can significantly reduce the incidence of pneumonia and hospital
      admission due to infections in patients with CVID.

PMID- 16604244
TI  - Clinical characteristics of dengue and dengue hemorrhagic fever in a medical
      center of southern Taiwan during the 2002 epidemic.
AB  - BACKGROUND AND PURPOSE: This study investigated the clinical manifestations and
      risk factors for dengue fever (DF) and dengue hemorrhagic fever (DHF) and disease
      severity during the 2002 outbreak in the Kaohsiung area. METHODS: We analyzed the
      clinical characteristics of 644 patients with virologically or serologically
      positive results for dengue virus at Kaohsiung Medical University Hospital from
      January 1 to December 31, 2002. RESULTS: The case rate peaked in November. The
      male-to-female ratio was 1:1.2 and the mean age was 47.5 +/- 17.9 years (range, 7
      months to 88 years). The criteria for DHF were fulfilled in 232 cases, including
      12 cases of dengue shock syndrome (DSS). The most common symptoms were fever
      (96.1%), myalgia (68.5%), headache (55.4%), and skin rash (53.7%). Hemorrhagic
      manifestations were noted in 73.0% of patients. The mean age of patients with
      DHF/DSS was 53.6 +/- 16.3 years, and the highest incidence occurred in those aged
      60-69 years (27.2%). Significant risk factors for DHF/DSS were age >65 years,
      diabetes mellitus, hypertension, and uremia. Gallbladder wall thickening was
      found in 64.7% of DHF cases who underwent abdominal ultrasound examination. 164
      of the 232 DHF cases (71%) were discharged without a diagnosis of DHF. The number
      of DHF cases identified by our study was nearly equal to that reported through
      the established passive surveillance system (232 cases vs 242). CONCLUSIONS: DHF
      was under-reported in hospital, suggesting that continuous surveillance and
      education for clinicians in the recognition of DHF, especially in elderly
      patients and those with chronic pre-existing comorbidities, is needed.

PMID- 16604245
TI  - OXA-type beta-lactamases among extended-spectrum cephalosporin-resistant
      Pseudomonas aeruginosa isolates in a university hospital in southern Taiwan.
AB  - BACKGROUND AND PURPOSE: Data on the epidemiology of OXA-type extended-spectrum
      beta (beta)-lactamases (ESBLs) are limited due to difficulty of identification by
      routine microbiology laboratories. We determined the prevalence rate of OXA-type
      beta-lactamases among extended-spectrum cephalosporin (ESC)-non-susceptible
      Pseudomonas aeruginosa isolates at a university hospital in southern Taiwan.
      METHODS: A total of 1,294 ESC-non-susceptible P. aeruginosa isolates collected
      between 1989 and 1996 (n = 42) and between December 1999 and December 2002 (n =
      1,252) were analyzed by polymerase chain reaction assays with primers specific
      for bla(OXA) genes and isoelectric focusing. RESULTS: Forty five isolates (3.5%)
      were found to produce an OXA-type beta-lactamase. Overall, 2 OXA-type ESBLs, OXA
      14 (n = 2) and OXA-17 (n = 35), were detected in 37 (2.9%) isolates, and the OXA
      10-type narrow-spectrum beta-lactamase was found in 8 (0.6%) isolates. OXA-10 and
      the 2 OXA-type ESBLs were detected in 6 (14.3%) and 4 (9.5%) of 42 ESC-non
      susceptible isolates collected between 1989 and 1996. OXA-10 and OXA-17 were
      detected in 2 (0.2%) and 33 (2.6%) of 1,252 ESC-non-susceptible isolates
      collected between December 1999 and December 2002. CONCLUSIONS: These data
      indicate that OXA-17 was the most common OXA-type ESBL and that OXA-type beta
      lactamases have decreased in ESC-non-susceptible P. aeruginosa at this hospital
      in recent years. Pulsed-field gel electrophoresis revealed clonal diversity among
      the OXA-producing isolates.

PMID- 16604246
TI  - Predominance of Gram-negative bacilli and increasing antimicrobial resistance in
      nosocomial bloodstream infections at a university hospital in southern Taiwan,
      1996-2003.
AB  - BACKGROUND AND PURPOSE: While nosocomial infections cause substantial morbidity
      and mortality, the availability of timely and accurate epidemiological
      information on nosocomial pathogens is essential to the appropriate selection of
      empirical therapy. This study analyzed nosocomial bloodstream infections (NBSIs)
      surveillance data to determine trends in the distribution of pathogens and
      antimicrobial susceptibilities of these pathogens. METHODS: During the period
      from 1996 to 2003 at National Cheng Kung University Hospital, patients with NBSIs
      were enrolled in the study, and the ranking of pathogens and status of
      antimicrobial resistance were determined. RESULTS: From 1996 to 2003, there were
      4,038 episodes of NBSIs. The overall incidence was 1.79 episodes per 1,000
      inpatient-days. Aerobic Gram-negative bacilli, Gram-positive cocci, fungi, and
      anaerobes were responsible for 51%, 37%, 10%, and 1.6% of NBSIs, respectively.
      The 5 leading pathogens were coagulase-negative staphylococci (16% of NBSIs),
      Staphylococcus aureus (13%), Candida spp. (10%), Acinetobacter baumannii (8%),
      and Escherichia coli (8%). Oxacillin resistance was found in 90% of coagulase
      negative staphylococci and 75% of S. aureus isolates. In contrast to Enterococcus
      faecalis, in which only 1% of isolates were resistant to ampicillin, 78% of
      Enterococcus faecium isolates were resistant to ampicillin. The emerging
      antimicrobial-resistant Gram-negative pathogens included multidrug-resistant A.
      baumannii, cephalosporin- or fluoroquinolone-resistant E. coli, and extended
      spectrum beta-lactamase producing Klebsiella pneumoniae and E. coli. Despite the
      annual increase in the use of fluconazole, Candida albicans (54%) remained the
      most common causative pathogen of nosocomial candidemia. CONCLUSIONS: In summary,
      Gram-negative bacilli predominated among pathogens causing NBSIs and an upsurge
      in the threat of antimicrobial resistance in our hospital occurred during the 8
      year period. Surveillance of the characteristics of NBSIs and antimicrobial
      resistance patterns, together with appropriate antibiotic and infection control
      measures, should be reinforced.

PMID- 16604247
TI  - Stenotrophomonas maltophilia bacteremia in pediatric patients-- a 10-year
      analysis.
AB  - BACKGROUND AND PURPOSE: Stenotrophomonas maltophilia bacteremia is an important
      cause of mortality among immunocompromised children. However, there has been
      little information concerning S. maltophilia bacteremia in the pediatric
      population. METHODS: We reviewed the drug susceptibility of bloodstream isolates
      of S. maltophilia and medical charts of S. maltophilia bacteremia patients less
      than 18 years old at the Department of Pediatrics, National Taiwan University
      Hospital from January 1993 to June 2003. The risk factors associated with
      mortality of the patients with S. maltophilia bacteremia were analyzed. RESULTS:
      In total, 32 episodes (31 patients) of S. maltophilia bacteremia were reviewed.
      The average rate of nosocomial bloodstream infection was 8.3 episodes per 100,000
      patient-days, and an average of 6.4% of them were caused by S. maltophilia.
      Malignancy was the most common underlying disease (32%). Six episodes of S.
      maltophilia bacteremia had soft tissue involvement, and only 1 of them underwent
      surgical intervention and survived. These 32 isolates were most susceptible to
      trimethoprim-sulfamethoxazole (91%), and no obvious increase in multidrug
      resistance was noted in the previous 10 years. The crude mortality rate was
      40.6%. Malignancy, failure to remove central venous catheter, and ineffective
      antibiotic treatment were significant risk factors for mortality. CONCLUSIONS:
      Early and effective antimicrobial therapy and removal of central venous catheter
      as soon as possible are vital for the successful management of S. maltophilia
      bacteremia.

PMID- 16604248
TI  - Clinical features and risk factors for mortality in Aeromonas bacteremic adults
      with hematologic malignancies.
AB  - BACKGROUND AND PURPOSE: Aeromonas spp. often cause infections in
      immunocompromised patients. To specifically understand the clinical features of
      Aeromonas bacteremic adults with hematologic malignancies, we investigated the
      demographic, clinical and microbiologic characteristics of Aeromonas bacteremia
      in this patient population. METHODS: Retrospective study performed in a tertiary
      medical center in southern Taiwan, in which adults with hematologic malignancies
      suffered from Aeromonas bacteremia admitted between 1995 and 2003 were included
      for study. RESULTS: There were 45 episodes of Aeromonas bacteremia in 41 adults
      with hematologic malignancies. Episodes of Aeromonas bacteremia which occurred at
      least 2 months apart were counted as separate cases in the analysis. A total of
      30 men and 15 women (mean age: 53.2 years), with 4 patients experiencing 2
      episodes, was included. The 3 leading underlying hematologic malignancies were
      acute myelogenous leukemia (37.8%), myelodysplastic syndrome (26.7%) and non
      Hodgkin's lymphoma (17.8%). No cluster of Aeromonas bacteremia was found during
      the study period. Twenty nine (64.4%) of the 31 patients with nosocomial
      Aeromonas bacteremia had received recent antineoplastic chemotherapy. The 3
      leading clinical manifestations were fever (88.9%), septic shock (40%), and
      altered consciousness (26.7%). Eleven (24.4%) episodes of bacteremia were
      polymicrobial. Sixteen (35.6%) patients died within 14 days of onset of
      bacteremia. The mean duration from sampling blood for culture to death was 3.81
      days. Altered consciousness (odds ratio, 8.999; 95% confidence interval, 1.787
      45.33; p=0.008) was the only independent prognostic factor for mortality. High
      resistance rates (11.1% to piperacillin and 35.6% to imipenem) among Aeromonas
      isolates were also noted. CONCLUSION: In febrile patients with hematologic
      malignancies and suspected Aeromonas infections, particular attention to the
      development of alteration of consciousness is needed as it is an independent risk
      factor for mortality.

PMID- 16604249
TI  - Risk factors for candidemia-related mortality at a medical center in central
      Taiwan.
AB  - BACKGROUND AND PURPOSE: Bloodstream infections due to Candida spp. are associated
      with significant mortality and morbidity. This study analysed the epidemiology
      and outcome of candidemia cases in a teaching hospital in central Taiwan.
      METHODS: We retrospectively studied the clinical characteristics and antifungal
      susceptibility of isolates and risk factors for mortality in 91 cases of
      candidemia treated from January 1, 2001 to June 30, 2003. RESULTS: The mean age
      of the patients was 67 years (range, 30-90 years). Three episodes (3%) were
      community acquired. Adequate antifungal therapy was given to 78 patients (78%).
      Cancer (38.5%) and diabetes mellitus (36.3%) were the 2 most common underlying
      diseases. The most frequent risk factors identified for candidemia were prior
      broad-spectrum antibiotic use (84.6%), central venous catheterization (83.5%) and
      Candida colonization (79.5%). The most frequent isolates were Candida albicans
      (64.8%) and Candida tropicalis (19.8%). All of the C. albicans and C. tropicalis
      isolates were sensitive to fluconazole (minimal inhibitory concentration <or=8
      microg/mL). Susceptibility to amphotericin B and fluconazole was found in 96.7%
      (88/91) and 95.6% (87/91) of Candida spp., respectively. Risk factors for
      mortality due to candidemia in the univariate analysis included central venous
      catheterization, shock, and high Acute Physiology and Chronic Health Evaluation
      II (APACHE II) score. APACHE II score was the only independent prognostic factor
      in the multivariate analysis. CONCLUSIONS: Candidemia has a high mortality rate
      and C. albicans remains the most common isolate. Fluconazole and amphotericin B
      maintained good in vitro antifungal activity against Candida spp. APACHE II score
      was the only independent factor for mortality in patients with candidemia.

PMID- 16604250
TI  - Pulmonary arterial hypertension in autoimmune diseases: an analysis of 19 cases
      from a medical center in northern Taiwan.
AB  - BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH), a serious
      complication of autoimmune diseases, has rarely been reported in Taiwan. METHODS:
      Nineteen patients with various autoimmune diseases diagnosed with PAH at Taipei
      Veterans General Hospital from 2002 to 2004 were enrolled; the underlying
      autoimmune diseases included systemic lupus erythematosus (n = 6), primary
      Sjogren's syndrome (n = 5), systemic sclerosis (n = 4), adult-onset Still's
      disease (n = 2), and mixed connective tissue disease (n = 2). The characteristic
      manifestations of underlying autoimmune diseases and the clinical features of PAH
      were analyzed. RESULTS: There were 16 female and 3 male patients. The median age
      at onset of PAH was 44 years and the mean right ventricular systolic pressure
      (RVSP) was 67.9 mm Hg. Patients without pneumonitis had a significantly higher
      RVSP value than those with pneumonitis (77.5 +/- 24.3 vs 54.8 +/- 18.4 mm Hg,
      p=0.041). Four out of 7 patients (57.1%) with RVSP >or=80 mm Hg and 1 out of 12
      patients (8.3%) with RVSP <80 mm Hg died. In all of the 19 patients, the severity
      of RVSP was significantly correlated with serum uric acid (UA) level (r = 0.686,
      p=0.001). Among the PAH patients without pneumonitis, the severity of RVSP
      inversely correlated with the diffusion capacity of the lung for carbon monoxide
      (DLCO) [r = -0.856, p=0.003]. The characteristic manifestations of underlying
      autoimmune diseases included a high incidence of Raynaud's phenomenon (15/19,
      78.9%), a high titer of antinuclear antibody (13/17, 76.5%), positive anti
      ribonucleoprotein antibody (8/15, 53.3%), hypergammaglobulinemia (15/19, 78.9%),
      hyperuricemia (13/19, 68.4%), and less renal involvement. CONCLUSIONS: PAH in
      autoimmune diseases could be potentially fatal with characteristic
      manifestations. Moreover, RVSP correlated directly with serum UA level and
      inversely with DLCO.

PMID- 16604251
TI  - Osteomyelitis as a late complication of Bacille Calmette-Guerin vaccination.
AB  - Bacille Calmette-Guerin (BCG) osteomyelitis is a very rare complication of BCG
      vaccination. We report a 14-month-old boy who received BCG vaccination at birth.
      He developed pain and swelling in his left calf at 11 months of age. BCG
      osteomyelitis was diagnosed in right femur and left tibia. He had no evidence of
      immunodeficiency. After antituberculous therapy and surgical treatment, the bone
      lesions disappeared and he was discharged from hospital without any sequela
      during 11 months of follow-up.

PMID- 16604252
TI  - Aldosterone and its blockade: a cardiovascular and renal perspective.
AB  - Aldosterone not only contributes to salt and water homeostasis, but also exerts
      direct cardiovascular and renal effects. Numerous experimental and clinical
      studies indicate that aldosterone participate in cardiac alterations associated
      with hypertension, heart failure, diabetes and other pathological entities. It is
      important to mention that dietary salt is a key factor in aldosterone-mediated
      cardiovascular damage, since damage was more evident in animals on a high-salt
      diet than animals on a low salt diet. A pathophysiological action of aldosterone
      involves development of extracellular matrix and fibrosis, inflammation,
      stimulation of reactive oxygen species production, endothelial dysfunction, cell
      growth and proliferation. Many studies showed local extra-adrenal production of
      aldosterone in brain blood vessel, and the heart, which contribute in an
      important manner to the pathological actions of this mineralocorticoid. Several
      studies such as RALES, EPHESUS, 4E and others, recently showed that
      mineralocorticoid-receptor (MR) antagonists, alone or in combination with ACE
      inhibitors or ARBs, reduced the risk of progressive target organ damage and
      hospitalization in patients with hypertension and heart failure. These clinical
      benefits support the therapeutic usefulness of MR antagonists.

PMID- 16604253
TI  - Effects of hyperbaric oxygen on inflammatory response to wound and trauma:
      possible mechanism of action.
AB  - There is growing interest in expanding the clinical applications for HBO2
      (hyperbaric oxygen therapy) into new medical and surgical fields. The
      pathophysiology of response towards wounds, infection, trauma, or surgery
      involves various chemical mediators that include cytokines, prostaglandins (PGs),
      and nitric oxide (NO). The beneficial role played by HBO2 in wound healing,
      carbon monoxide poisoning, decompression sickness, and other indications is well
      documented. However, the exact mechanism of action is still poorly understood.
      This review addresses the effects of HBO2 on PGs, NO, and cytokines involved in
      wound pathophysiology and inflammation in particular. The results of this review
      indicate that HBO2 has important effects on the biology of cytokines and other
      mediators of inflammation. HBO2 causes cytokine down-regulation and growth factor
      up-regulation. HBO2 transiently suppresses stimulus-induced proinflammatory
      cytokine production and affects the liberation of TNFa (tumor necrosis factor
      alpha) and endothelins. VEGF (vascular endothelial growth factor) levels are
      significantly increased with HBO2, whereas the value of PGE2 and COX-2 mRNA are
      markedly reduced. The effect of HBO2 on NO production is not well established and
      more studies are required. In conclusion, cytokines, PGs, and NO may play a major
      role in the mechanism of action of HBO2 and further research could pave the way
      for new clinical applications for HBO2 to be established. It could be proposed
      that chronic wounds persist due to an uncontrolled pathological inflammatory
      response in the wound bed and that HBO2 enhances wound healing by damping
      pathological inflammation (anti-inflammatory effects); this hypothetical proposal
      remains to be substantiated with experimental results.

PMID- 16604254
TI  - Microbial-induced regulation of syndecan expression: important host defense
      mechanism or an opportunity for pathogens?

PMID- 16604255
TI  - Proteoglycans are differentially altered in muscular dystrophies.

PMID- 16604256
TI  - Common neuroprotective effects of endothelin receptor a blockade and
      erythropoietin during hypoxia-associated cell injury. Perspectives of combined
      treatment.

PMID- 16604257
TI  - Impairment of the activity of glycosaminoglycan-binding cytokines by functionally
      abnormal heparan sulfates: a novel mechanism underlying disease pathophysiology.

PMID- 16604258
TI  - Transmembrane domain-dependent functional oligomerization of syndecans.
AB  - Cell surface adhesion receptors of the syndecan family initiate intracellular
      events through clustering of receptors. This crucial clustering occurs through
      receptor dimerization or oligomerization, which is mediated by receptor
      transmembrane domains. However, the exact role of the transmembrane domain during
      receptor activation is not fully understood. Researchers have not yet determined
      whether the transmembrane domain functions solely in the physical aspects of
      receptor clustering, or whether the domain has additional functional roles. Here
      we review recent advances in understanding the functionality of transmembrane
      domain-dependent oligomerization of syndecan cell adhesion receptor.

PMID- 16604259
TI  - Repeat intrathecal triamcinolone acetonide application reduces acute occurring
      painful dysesthesia in patients with relapsing remitting multiple sclerosis.
AB  - We describe four patients with relapsing remitting multiple sclerosis (RRMS) who
      experienced a relapse with acute onset of painful sensations. Pain sensations
      disappeared in two of them and markedly reduced in the other ones after repeat
      application of intrathecal triamcinolone acetonide (TCA) following a prior
      unsuccessful treatment with intravenous steroids. TCA administration was well
      tolerated and no serious side effects occurred. Repeated intrathecal TCA
      injection may provide a substantial benefit in RRMS patients with acute onset of
      pain due to an inflammatory lesion within the spinal cord.

PMID- 16604260
TI  - Quality control system of the endoplasmic reticulum and related diseases.
AB  - The quality control (QC) system of the endoplasmic reticulum (ER) is an important
      monitoring mechanism in the protein maturation process, which ensures export of
      properly folded proteins from the ER. Incorrectly or incompletely folded proteins
      are retained in the ER for refolding or degradation by the ER-residing
      proteasome. The calnexin/calreticulin cycle and ER-associated degradation are the
      key elements in QC. These two mechanisms work together to allow incorrectly
      folded proteins have additional opportunities to achieve their native
      conformations. The QC dysfunction is involved in many diseases caused by mutant
      proteins, many of which are causes of neurodegenerative disorders. A better
      understanding of molecular regulation in the QC system will uncover the molecular
      pathogenic mechanisms of many diseases caused by protein misfolding and help
      discover novel strategies for preventing or treating these diseases.

PMID- 16604261
TI  - Two observed regions in B lymphocyte stimulator important for its biological
      activity.
AB  - B lymphocyte stimulator (BLyS), a member of the tumor necrosis factor superfamily
      of ligands, is a crucial survival factor for B cells. We successfully constructed
      seven mutants of the functional soluble fragment of human BLyS (named cBLyS,
      amino acid 134-285), including three deletion mutants and four site-directed
      mutants. All the mutant proteins were expressed in Escherichia coli and purified
      by Ni-NTA affinity chromatography. The biological activities of these mutants
      were assessed by the ligand-receptor binding assay, B cell proliferation assay
      and immune effect response in vivo. Our results indicated that four residues,
      H218, F220, T228 and L229, are indispensable for the biological activity of
      cBLyS, whereas two regions, amino acid 134-148 and amino acid 271-285, are
      related to the biological activity of BLyS. The protein of deletion of amino acid
      134-148 leads to a complete defection in raising the antigen-specific IgM titer.
      The deletion of amino acid 271-285 reduces the effectiveness compared with the
      native cBLyS. This indicates that the region of amino acid 134-148 is
      indispensable for cBLyS to function normally.

PMID- 16604262
TI  - Study of the antifungal ability of Bacillus subtilis strain PY-1 in vitro and
      identification of its antifungal substance (iturin A).
AB  - A Bacillus strain, denoted as PY-1, was isolated from the vascular bundle of
      cotton. Biochemical, physiological and 16S rDNA sequence analysis proved that it
      should belong to Bacillus subtilis. The PY-1 strain showed strong ability against
      many common plant fungal pathogens in vitro. The antibiotics produced by this
      strain were stable in neutral and basic conditions, and not sensitive to high
      temperature. From the culture broth of PY-1 strain, five antifungal compounds
      were isolated by acidic precipitation, methanol extraction, gel filtration and
      reverse-phase HPLC. Advanced identification was performed by mass spectrometry
      and nuclear magnetic resonance spectroscopy. These five antifungal compounds were
      proved to be the isomers of iturin A: A2, A3, A4, A6 and A7. In fast atom
      bombardment mass spectrometry/mass spectrometry collision-induced dissociation
      spectra, fragmentation ions from two prior linear acylium ions were observed, and
      the prior ion, Tyr-Asn-Gln-Pro-Asn-Ser-betaAA-Asn-CO+, was first reported.

PMID- 16604263
TI  - Neuroprotection of insulin against oxidative stress-induced apoptosis in cultured
      retinal neurons: involvement of phosphoinositide 3-kinase/Akt signal pathway.
AB  - In order to investigate the neuroprotection of insulin in retinal neurons, we
      used retinal neuronal culture as a model system to study the protective effects
      of insulin against H2O2-induced cytotoxicity and apoptotic death. Primary retinal
      neuronal cultures were grown from retinas of 0-2-day old Sprague-Dawley rats.
      Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay. Apoptotic cell death was evaluated by the TdT-mediated
      digoxigenin-dUTP nick-end labeling assay, and by DNA laddering analysis.
      Phosphoinositide 3-kinase (PI3K) activity was measured using phosphoinositide 4,5
      bisphophate and [gamma-32P]ATP as substrate. Western blot analysis with anti
      phospho-Akt (pS473) antibody was performed to examine the level of phosphorylated
      Akt. We observed that treatment with 100 microM H2O2 for 24 h significantly
      decreased cell viability and induced apoptotic death of retinal neurons, and that
      pretreatment with 10 nM insulin significantly inhibited or attenuated H2O2
      induced cytotoxicity and apoptosis. Pretreatment with LY294002, a specific PI3K
      inhibitor, abolished the cytoprotective effect of insulin. Insulin also strongly
      activated both PI3K and the downstream effector Akt. These results suggest that
      insulin protects retinal neurons from oxidative stress-induced apoptosis and that
      the PI3K/Akt signal pathway is involved in insulin-mediated retinal
      neuroprotection.

PMID- 16604264
TI  - Isoform of vascular endothelial cell growth inhibitor (VEGI72-251) increases
      interleukin-2 production by activation of T lymphocytes.
AB  - The objective of this study is to investigate the characteristics of the
      recombinant variant of human vascular endothelial cell growth inhibitor, VEGI72
      251, and compare its biological activities with that of its prototype VEGI24-174.
      The recombinant plasmid containing the variant VEGI72-251 gene was constructed
      and expressed in Escherichia coli. The effects of the expressed VEGI72-251 on
      cell proliferations were checked in the human umbilical vein endothelial cell
      line and certain tumor cell lines (ECV304 and B16). The inhibition of VEGI72-251
      on angiogenesis was detected in the chorioallantoic membrane of chick embryos. In
      comparison with VEGI24-174, the recombinant human VEGI72-251 seems to have no
      effect on the proliferation of endothelial cells and the angiogenesis of the
      chorioallantoic membrane in vitro. An enzyme-linked immunosorbent assay-based
      method was used for the measurement of interleukin-2 (IL-2) production by
      peripheral blood monocytes (PBMCs) treated with VEGI72-251. PBMCs were pretreated
      with VEGI72-251 (1.25-12.50 microg/ml) for 24 h in vitro, and the IL-2
      concentration in PBMC medium was increased from 354 pg/ml to 1256 pg/ml. It can
      be concluded that VEGI72-251 is able to increase the level of human IL-2
      production by the activation of T lymphocytes. Differing from VEGI24-174 on anti
      angiogenesis, VEGI72-251 may serve as an anti-cancer factor through its
      activation of T lymphocytes.

PMID- 16604265
TI  - Treatment with vector-expressed small hairpin RNAs against Ki67 RNA-induced cell
      growth inhibition and apoptosis in human renal carcinoma cells.
AB  - Short hairpin RNAs (shRNAs) transcribed by RNA polymerase III promoters can
      trigger sequence-selective gene silencing in mammalian cells. By virtue of their
      excellent function in knocking down expression of cancer-associated genes, shRNAs
      could be used as new therapeutic agents for cancer. As overexpression of Ki67 in
      renal cancer has been correlated to a more aggressive tumor phenotype, inhibition
      of Ki67 protein expression by means of shRNAs seems to be a promising approach
      for the therapy of renal cancer. In this study, we constructed an expression
      plasmid encoding shRNAs against the Ki67 gene, named pSilencerKi67, and
      transfected it into human renal carcinoma cells. The pSilencerKi67 was shown to
      significantly knock down the expression of the Ki67 gene in human renal carcinoma
      cells, resulting in inhibiting proliferation and inducing apoptotic cell death
      that can be maintained for at least 6 d. These findings offer the promise of
      using vector-based shRNAs against Ki67 in renal cancer gene therapy.

PMID- 16604266
TI  - Virulence phenotyping and molecular characterization of a low-pathogenicity
      isolate of Listeria monocytogenes from cow's milk.
AB  - A low-pathogenicity isolate of Listeria monocytogenes from cow's milk, as
      screened in mouse and chicken embryonated egg models, was examined for virulence
      related phenotypic traits. Corresponding virulence genes (iap, prfA, plcA, hly,
      mpl, actA, plcB, InlA and InlB) were compared with L. monocytogenes reference
      strains 10403S and EGD to elucidate the possible molecular mechanisms of low
      virulence. Although L. monocytogenes H4 exhibited similar patterns to strain
      10403S in terms of hemolytic activity, in vitro growth and invasiveness and even
      had higher adhesiveness, faster intracellular growth and higher phospholipase
      activity in vitro, it was substantially less virulent than the strain 10403S in
      mouse and chicken embryo models (50% lethal dose: 10(8.14) vs. 10(5.49) and
      10(6.73) vs. 10(1.9), respectively). The genes prfA, plcA and mpl were homologous
      among L. monocytogenes strains H4, 10403S and EGD (>98%). Genes iap, hly, plcB,
      InlA and InlB of L. monocytogenes 10403S had higher homology to those of strain
      EGD (>98%) than isolate H4. The homology of the gene hly between strain 10403S
      and isolate H4 was 96.9% at the nucleotide level, but 98.7% at the amino acid
      level. The actA gene of isolate H4 had deletions of 105 nucleotides corresponding
      to 35 amino acid deletions falling within the proline-rich region. Taken
      together, this study presents some clues as to reduced virulence to mice and
      chicken embryos of the isolate H4 probably as a result of deletion mutations of
      actA.

PMID- 16604267
TI  - cvhA gene of Streptomyces hygroscopicus 10-22 encodes a negative regulator for
      mycelia development.
AB  - A five-gene cluster cvhABCDE was identified from Streptomyces hygroscopicus 10
      22. As the first gene of this cluster, cvhA encoded a putative sensor histidine
      kinase with a predicted sensor domain consisting of two trans-membrane segments
      at the N-terminus and a conserved HATPase_c domain at the C-terminus. The C
      terminus polypeptide of CvhA expressed in Escherichia coli was purified and shown
      to be autophosphorylated with [gamma-32P]ATP in vitro. The phosphoryl group was
      acid-labile and basic-stable, which supported histidine as the phosphorylation
      residue. No obvious difference of mycelia development was observed between the
      null mutant of cvhA generated by targeted gene replacement and the wild-type
      parental strain 10-22 grown on solid soya flour medium with 2%-8% glucose or
      sucrose, but the cvhA mutant could form much more abundant aerial mycelia and
      spores than the wild-type strain on solid soya flour medium supplemented with 6%
      8% mannitol, 6%-8% sorbitol, 4%-6% mannose, or 4%-6% fructose. This phenotype was
      complemented by the cloned wild-type cvhA gene, and no difference was observed
      for growth curves of the cvhA mutant and the wild strain in liquid minimal medium
      with the tested sugars at a concentration of 4%, 6% and 8%. We thus propose that
      CvhA is likely a sensor histidine kinase and negatively regulates the
      morphological differentiation in a sugar-dependent manner in S. hygroscopicus 10
      22.

PMID- 16604268
TI  - Expression of MaMAPK gene in seedlings of Malus L. under water stress.
AB  - Seedlings of three species of Malus were used to study the expression of mitogen
      activated protein kinase (MAPK) in response to water stress: Malus hupehensis, a
      drought-sensitive species; Malus sieversii, a drought-tolerant species; and Malus
      micromalus, a middle type. Results showed that Malus MAPK (MaMAPK, GenBank
      accession No. AF435805) was expressed in both roots and leaves of seedlings of
      the three Malus species treated with 20% polyethylene glycol for different time
      periods. Expression levels peaked at 1.5 h after treatment with polyethylene
      glycol, then decreased to their lowest levels. Liquid kinase assays indicated
      that the dynamic changes of MAPK activity were very similar to those of the
      relative expression of MaMAPK mRNA. However, the peak of the former occurred
      slightly behind the latter. It was noticed that, although the kinase activity
      decreased after the peak, it was still higher than that of the control during the
      whole time period. These results suggested that MaMAPK was regulated not only by
      water stress at the transcription level, but also by phosphorylation and
      dephosphorylation at the protein level. In addition, of these three apple
      species, the highest MAPK activity and MaMAPK expression level was found in M.
      sieversii, followed by M. micromalus and M. hupehensis, suggesting that MAPK
      might be correlated with drought tolerance in these three species. The different
      expression levels might be one of the molecular mechanisms of the different
      drought tolerances in Malus.

PMID- 16604269
TI  - cDNA cloning of two novel T-superfamily conotoxins from Conus leopardus.
AB  - The full-length cDNAs of two novel T-superfamily conotoxins, Lp5.1 and Lp5.2,
      were cloned from a vermivorous cone snail Conus leopardus using 3'/5'-rapid
      amplification of cDNA ends. The cDNA of Lp5.1 encodes a precursor of 65 residues,
      including a 22-residue signal peptide, a 28-residue propeptide and a 15-residue
      mature peptide. Lp5.1 is processed at the common signal site-X-Arg- immediately
      before the mature peptide sequences. In the case of Lp5.2, the precursor includes
      a 25-residue signal peptide and a 43-residue sequence comprising the propeptide
      and mature peptide, which is probably cleaved to yield a 29-residue propeptide
      and a 14-residue mature toxin. Although these two conotoxins share a similar
      signal sequence and a conserved disulfide pattern with the known T-superfamily,
      the pro-region and mature peptides are of low identity, especially Lp5.2 with an
      identity as low as 10.7% compared with the reference Mr5.1a. The elucidated cDNAs
      of these two toxins will facilitate a better understanding of the species
      distribution, the sequence diversity of T-superfamily conotoxins, the special
      gene structure and the evolution of these peptides.

PMID- 16604270
TI  - A descriptive study of pathways to care among hospitalized urban African American
      first-episode schizophrenia-spectrum patients.
AB  - BACKGROUND: Studying pathways to care, or contacts made during the period of time
      from the onset of illness until the first initiation of treatment, is critical
      for understanding how to improve the early recognition and treatment of mental
      disorders. However, little is known about pathways to care among patients with
      first-episode psychosis in the United States. The objectives of this study were
      to examine the pathways to care and number of help contacts prior to
      hospitalization in first-episode patients, and to ascertain the frequency of
      contact with primary care providers and police. METHOD: Pathways to care,
      including all contacts for help from the onset of prodromal symptoms until first
      hospital admission, were assessed in 25 urban African American patients. Other
      measures were obtained as part of an ongoing study of predictors of the duration
      of untreated psychosis. RESULTS: The median durations from the onset of illness
      to hospital admission and from the emergence of positive psychotic symptoms to
      hospital admission were 128.0 weeks (range 0.6-476.9) and 32.9 weeks (range 0.4
      337.7), respectively. Of the 83 total contacts, 17 were with police, whereas only
      four were with primary care providers. While the number of contacts per patient
      ranged from one to eight, 16 of the 25 patients were admitted within 1 week of
      their first contact for help. CONCLUSIONS: The findings indicate that pathways to
      care in this population are highly variable, and there is a need for additional
      research to better understand the nature and determinants of these pathways. Such
      investigations may provide insights into service enhancements that can promote
      early detection and intervention, thus improving illness outcomes.

PMID- 16604271
TI  - Who visits the psychiatric emergency room for the first time?
AB  - OBJECTIVE: To examine patient and system characteristics of first-time
      ("incident") vs. recurrent ("recurrent") use of a psychiatric emergency room
      (PER). METHODS: Data on demographic and clinical characteristics and health
      service utilization were collected for incident and recurrent users (n=3,719) who
      visited the PER of the university hospital in Leuven, Belgium, between March 2000
      and March 2002. RESULTS: About 64% (n=2,368) were incident and 36% (n=1,351) were
      recurrent users. The PER was the first treatment setting ever for 50% of the
      incident users. Incident users were most likely over 69 years (OR=2.84, P<0.001),
      employed (OR=2.21, P<0.001), or referred by a health care professional (OR=1.72,
      P<0.001). They were less likely to have a personality disorder (OR=0.40, P<0.001)
      or to have used inpatient or outpatient services in the past (OR's 0.11 and 0.65,
      respectively, P<0.001). About 44% were admitted, 38% referred for outpatient
      treatment, 9% referred to the outpatient crisis-intervention program, and 9%
      refused any follow-up. CONCLUSIONS: The PER was a first treatment setting ever
      for 1 in 3 patients. Incident and recurrent users differed in sociodemographic
      characteristics, pathways to care, service use, and the presence of a personality
      disorder. They did not differ in axis 1 disorders, comorbid mental disorders, or
      pathways after care.

PMID- 16604272
TI  - Depressive episodes in Sardinian emigrants to Argentina: why are females at risk?
AB  - BACKGROUND/OBJECTIVE: To compare the frequency of ICD-10 depressive episodes in a
      community sample of Sardinian immigrants in Argentina and a community sample of
      Sardinian residents in Sardinia, Italy. METHOD: A search of telephone directories
      provided all subscribers with Sardinian surnames in the Argentinean area
      involved. A 75.8% of all subjects thus identified took part in the study (n =
      210). The characteristics of randomisation methods used to identify the community
      sample in Sardinia (n = 1040) have already been published elsewhere. All subjects
      were interviewed using the Composite International Diagnostic Interview
      Simplified. RESULTS: A higher frequency of depressive disorders was observed
      among the Sardinian immigrants in Argentina (26.7 vs. 13.5%, P < 0.0001). Females
      in particular showed a higher risk with respect to the Sardinian sample resident
      in Sardinia. DISCUSSION: On comparison of the present findings with the lifetime
      rate of depressive episodes in Sardinian immigrants in Paris (France), reported
      in a previous research study, a lower prevalence was observed among the latter
      group than in Sardinian immigrants in Argentina but the young male immigrants in
      Paris were at risk. CONCLUSION: The results obtained seem to suggest that
      emigration to a country where economic conditions have since dramatically changed
      may predispose subjects to depressive disorders, particularly when compared to
      the percentage of affected subjects in their native population and among subjects
      who had emigrated to more economically stable countries. Further epidemiological
      studies are warranted in order to confirm the present results and to clarify the
      determinants of the major risk for females in such a condition.

PMID- 16604273
TI  - Regulation of expression of the arabinose and glucose transporter genes in the
      thermophilic archaeon Sulfolobus solfataricus.
AB  - Sugar uptake in Sulfolobus solfataricus, a thermoacidophilic archaeon, occurs
      through high-affinity binding of protein-dependent ABC transporters. We have
      investigated the expression patterns of two sugar transport operons, that is, the
      glucose and arabinose transporters. Analysis of the araS promoter activity, and
      the mRNA and protein levels in S. solfataricus cells grown on different carbon
      sources showed that expression of the arabinose transporter gene cluster is
      highly regulated and dependent on the presence of arabinose in the medium.
      Glucose in the growth medium repressed the expression of the arabinose transport
      genes. By means of primer extension, the transcriptional start site for the
      arabinose operon was mapped. Interestingly, expression of the arabinose
      transporter is down-regulated by addition of a selective set of amino acids to
      the medium. Expression of the glucose transporter genes appeared constitutive.
      These data confirm the earlier observation of a catabolite repression-like system
      in S. solfataricus.

PMID- 16604274
TI  - Isolation and characterization of a novel thermophilic Bacillus strain degrading
      long-chain n-alkanes.
AB  - A thermophilic Bacillus strain NG80-2 growing within the temperature range of 45
      73 degrees C (optimum at 65 degrees C) was isolated from a deep subterranean oil
      reservoir in northern China. The strain was able to utilize crude oil and liquid
      paraffin as the sole carbon sources for growth, and the growth with crude oil was
      accompanied by the production of an unknown emulsifying agent. Further
      examination showed that NG80-2 degraded and utilized only long-chain (C15-C36) n
      alkanes, but not short-chain (C8-C14) n-alkanes and those longer than C40. Based
      on phenotypic and phylogenic analyses, NG80-2 was identified as Geobacillus
      thermodenitrificans. The strain NG80-2 may be potentially used for oily-waste
      treatment at elevated temperature, a condition which greatly accelerates the
      biodegradation rate, and for microbial enhancing oil recovery process.

PMID- 16604275
TI  - Structural analysis of the HiPIP from the acidophilic bacteria: Acidithiobacillus
      ferrooxidans.
AB  - Hip is a high-potential iron-sulfur protein (HiPIP) isolated from the acidophilic
      bacterium, Acidithiobacillus ferrooxidans. In the present work, a structural
      model of Hip suggests that the role of proline residues is essential to stabilize
      the protein folding at very low pH. The presence of an unusual disulfide bridge
      in Hip is demonstrated using mass spectrometry and nuclear magnetic resonance.
      This disulfide bridge is necessary to anchor the N-terminal extremity of the
      protein, but is not involved in the acid stability of Hip. The structural
      parameters correlated with the pH dependence of Hip redox potential are also
      analysed on the basis of this model. Given that the same structural features can
      enhance acidic stability and lead to elevated redox potentials, modulation of the
      redox potentials of electron carriers may be necessary to achieve electron
      transfer at very low pH.

PMID- 16604276
TI  - Hand preferences in captive orangutans (Pongo pygmaeus).
AB  - The strength of the evidence for population-level handedness in the great apes is
      a topic of considerable debate, yet there have been few studies of handedness in
      orangutans. We conducted a study of manual lateralization in a captive group of
      eight orangutans (Pongo pygmaeus) ranking the degrees of manual preference
      according to a defined framework. We analyzed five behavioral patterns: eat (one-
      and two-handed), make/modify tool, oral tool-use, and manual tool-use. Although
      some individuals showed significant manual preferences for one or more tasks, at
      the group-level both one-handed and two-handed eating, oral tool-use, and
      make/modify tool were ranked at level 1 (unlateralized). Manual tool-use was
      ranked at level 2, with four subjects demonstrating significant hand preferences,
      but no group-level bias to the right or left. Four subjects also showed hand
      specialization to the right or left across several tasks. These results are
      consistent with most previous studies of manual preference in orangutans. The
      emergence of manual lateralization in orangutans may relate to more complex
      manipulative tasks. We hypothesize that more challenging manual tasks elicit
      stronger hand preferences.

PMID- 16604277
TI  - Smoothening transition of a two-dimensional pressurized polymer ring.
AB  - We revisit the problem of a two-dimensional polymer ring subject to an inflating
      pressure differential. The ring is modeled as a freely jointed closed chain of N
      monomers. Using a Flory argument, mean-field calculation and Monte Carlo
      simulations, we show that at a critical pressure, p(c) approximately N(-1), the
      ring undergoes a second-order phase transition from a crumpled, random-walk
      state, where its mean area scales as <A> approximately N, to a smooth state with
      <A> approximately N(2). The transition belongs to the mean-field universality
      class. At the critical point a new state of polymer statistics is found, in which
      <A> approximately N(3/2). For p >> p(c) we use a transfer-matrix calculation to
      derive exact expressions for the properties of the smooth state.

PMID- 16604278
TI  - Preparation and characterization of (PVP + NaClO4) electrolytes for battery
      applications.
AB  - A sodium ion-conducting polymer electrolyte based on polyvinyl pyrrolidone (PVP)
      complexed with NaClO(4) was prepared using the solution-cast technique. The
      cathode film of V(2)O(5) xerogel modified with polyvinyl pyrrolidone was prepared
      using the sol-gel method. Investigations were conducted using X-ray
      diffractometry (XRD), Fourier transformation infrared (FT-IR) spectroscopy. The
      ionic conductivity and transference number measurements were performed to
      characterize the polymer electrolyte for battery applications. The transference
      number data indicated that the conducting species in these electrolytes are the
      anions. Using the electrolyte, electrochemical cells with a configuration Na/(PVP
      + NaClO(4))/V(2)O(5) modified by (PVP) were fabricated and their discharge
      profiles studied.

PMID- 16604279
TI  - Pinning-depinning of the contact line on nanorough surfaces.
AB  - We study the pinning-depinning phenomenon of a contact line on a solid surface
      decorated by a random array of nanometric structures. For this purpose, we have
      investigated the contact angle hysteresis behaviour of six different wetting and
      non-wetting fluids with surface tensions varying from 25 to 72mN m(-1). For low
      values of the areal density of defects phi(d), the hysteresis H increases
      linearly with phi(d) indicating that "individual" defects pin the contact line.
      Then, from a given value of phi(d), the hysteresis H becomes to decrease with
      increasing phi(d), indicating a new kind of collective depinning. These two
      regimes were observed for all fluids used. In both cases, our experimental
      results are compared with the theoretical predictions for contact angle
      hysteresis induced by single or multiple topographical defects. We ascribe the
      decrease of H to the formation of cavities along the wetting front.

PMID- 16604280
TI  - High osteoblastic activity in C3H/HeJ mice compared to C57BL/6J mice is
      associated with low apoptosis in C3H/HeJ osteoblasts.
AB  - This study sought to confirm that osteoblasts of C3H/HeJ (C3H) mice, which have
      higher differentiation status and bone-forming ability compared to C57BL/6J (B6)
      osteoblasts, also have a lower apoptosis level and to test whether the higher
      differentiation status and bone-forming ability of C3H osteoblasts were related
      to the lower apoptosis. C3H mice had 50% fewer (P < 0.01) apoptotic osteoblasts
      on the endocortical bone surface than B6 mice as determined by the TUNEL assay.
      Primary C3H osteoblasts in cultures also showed a 50% (P < 0.05) lower apoptosis
      level than B6 osteoblasts assayed by acridine orange/ethidium bromide staining of
      apoptotic osteoblasts. The lower apoptosis in C3H osteoblasts was accompanied by
      22% (P < 0.05) and 56% (P < 0.001) reduction in the activity of total caspases
      and caspases 3/7, respectively. C3H osteoblasts also displayed greater alkaline
      phosphatase (ALP) activity (P < 0.001) and higher expression of Cbfa1, type-1
      collagen, osteopontin, and osteocalcin genes (P < 0.05 for each). To assess if an
      association existed between population apoptosis and the differentiation status
      (ALP-specific activity) and/or bone-forming activity (insoluble collagen
      synthesis), C3H and B6 osteoblasts were treated with several apoptosis enhancers
      (tumor necrosis factor-alpha, dexamethasone, lipopolysaccharide, etoposide) and
      inhibitors (parathyroid hormone, insulin-like growth factor I, transforming
      growth factor beta1, estradiol). Both ALP (r = -0.61, P < 0.001) and insoluble
      collagen synthesis (r = -0.61, P < 0.001) were inversely correlated with
      apoptosis, suggesting that differentiation (maturation) and/or bone-forming
      activity of these mouse osteoblasts were inversely associated with apoptosis. In
      conclusion, these studies support the premise that higher bone density and bone
      formation rate in C3H mice could be due in part to lower apoptosis in C3H
      osteoblasts.

PMID- 16604281
TI  - Association of grip strength change with menopausal bone loss and related
      fractures: a population-based follow-up study.
AB  - The aim of the present study was to investigate the association between grip
      strength change and bone health according to menopausal status. A random sample
      of 971 pre- to postmenopausal women from the Kuopio Osteoporosis Risk Factor and
      Prevention (OSTPRE) study cohort was measured with dual X-ray absorptiometry in
      the lumbar spine (LS) and femoral neck (FN) and grip strength with pneumatic
      squeeze dynamometer at baseline (1989-1991), 5 years (1994-1997), and 10 years
      (1999-2001). Fractures were recorded based on self-reports and validated from
      medical records. Women were divided into two groups according to change in grip
      strength quartile from baseline to 5-year follow-up: not improved (n = 735) and
      improved (n = 236). In the total population, the greatest bone loss was observed
      in perimenopausal (beginning of menopause during follow-up, n = 311) women [P <
      0.001 vs. premenopausal women (n = 139)], and it declined in postmenopausal (n =
      521) women [P < 0.001 by analysis of covariance (ANCOVA)]. The perimenopausal
      bone loss rate was significantly lower in women in the improved group in
      comparison to the not improved group (P < 0.01) in contrast to the pre- and
      postmenopausal groups (P > 0.05). Accordingly, there was a greater decline in
      perimenopausal LS and FN T-scores in the improved group vs. the not improved
      group over the first 5-year follow-up interval (P < 0.05 by ANCOVA) and remained
      unchanged over the 10-year follow-up. In perimenopausal women, there was a trend
      toward higher fracture-free survival rate in the improved group (82%) vs. the not
      improved group (88%) after 10 years. Adjustments did not change the results. In
      conclusion, maintenance of grip strength is associated with menopausal bone loss
      and future fractures.

PMID- 16604282
TI  - Effects of lanthanum on composition, crystal size, and lattice structure of femur
      bone mineral of Wistar rats.
AB  - The application of lanthanum (La) in industry, medicine, and agriculture may
      cause accumulation of the element in human body. This article examines the
      effects of La on the femur bone mineral of male Wistar rats after administration
      of La(NO3)3 by gavage at the dose of 2.0 mg La(NO3)3.kg(-1).day(-1) over a 6
      month period. Chemical analysis confirmed La accumulation in bone and loss in
      bone mineral. Thermogravimetric analysis showed a decrease in the mineral-to
      matrix ratio and an increase in carbonate content. Fourier-transform infrared
      spectrometry revealed elevation in the contents of labile carbonate and acidic
      phosphate. The synchrotron radiation small-angle X-ray scattering study presented
      a smaller mean thickness of the mineral crystals in the bone of La-treated rats.
      The synchrotron radiation-extended X-ray absorption fine structure analysis
      indicated that the La treatment resulted in a lowered disorder in the crystals.
      The smaller size, more adsorbed labile carbonate, and more acidic phosphate made
      the bone mineral easier to dissolve, as revealed in the kinetic measurement of
      bone demineralization. These findings suggest that La retards bone maturation of
      rats.

PMID- 16604283
TI  - Partial prevention of long-term femoral bone loss in aged ovariectomized rats
      supplemented with choline-stabilized orthosilicic acid.
AB  - Silicon (Si) deficiency in animals results in bone defects. Choline-stabilized
      orthosilicic acid (ch-OSA) was found to have a high bioavailability compared to
      other Si supplements. The effect of ch-OSA supplementation was investigated on
      bone loss in aged ovariectomized (OVX) rats. Female Wistar rats (n = 58, age 9
      months) were randomized in three groups. One group was sham-operated (sham, n =
      21), and bilateral OVX was performed in the other two groups. OVX rats were
      supplemented orally with ch-OSA over 30 weeks (OVX1, n = 20; 1 mg Si/kg body
      weight daily) or used as controls (OVX0, n = 17). The serum Si concentration and
      the 24-hour urinary Si excretion of supplemented OVX rats was significantly
      higher compared to sham and OVX controls. Supplementation with ch-OSA
      significantly but partially reversed the decrease in Ca excretion, which was
      observed after OVX. The increase in bone turnover in OVX rats tended to be
      reduced by ch-OSA supplementation. ch-OSA supplementation increased significantly
      the femoral bone mineral content (BMC) in the distal region and total femoral BMC
      in OVX rats, whereas lumbar BMC was marginally increased. Femoral BMD was
      significantly increased at two sites in the distal region in OVX rats
      supplemented with ch-OSA compared to OVX controls. Total lumbar bone mineral
      density was marginally increased by ch-OSA supplementation. In conclusion, ch-OSA
      supplementation partially prevents femoral bone loss in the aged OVX rat model.

PMID- 16604285
TI  - Coronary calcification and osteoporosis in men and postmenopausal women are
      independent processes associated with aging.
AB  - The objective of this study was to investigate whether low bone mass is directly
      associated with the severity of coronary atherosclerosis in men and
      postmenopausal women self-referred for evaluation of coronary atherosclerosis and
      osteoporosis. Low bone mass was evaluated by measurement of bone mineral density
      (BMD) using quantitative computerized tomography (QCT). Coronary atherosclerosis
      was evaluated by measurement of coronary calcium (CC) burden using electron beam
      computerized tomography (EBCT). Using a cross-sectional design, we tested the
      hypothesis that osteoporosis and coronary atherosclerosis are correlated, age
      dependent processes. Study variables were BMD, CC scores, and other known risk
      factors for osteoporosis and atherosclerosis. Qualifying for the study were 313
      postmenopausal women and 167 men. Men had higher baseline CC scores and higher
      body mass indexes compared to women. In females, those patients with coronary
      calcification were older and had significantly lower BMD compared to those
      without calcification. In males, those patients with coronary calcification were
      older. By univariate correlation analysis, the degree of coronary calcification
      was inversely associated with BMD in postmenopausal women (P < 0.0001) but not in
      men. However, after controlling for age, this association was absent for both men
      and postmenopausal women. Using multivariate logistic regression analysis in
      women and men separately, age was the only significant predictor of positive CC
      status and low BMD. Our study suggests that in postmenopausal women and in men,
      after controlling for age, osteoporosis and coronary atherosclerosis are
      independent processes.

PMID- 16604284
TI  - Genetic and environmental correlations of bone mineral density at different
      skeletal sites in females and males.
AB  - Bone mineral density (BMD) is a complex trait having genetic and environmental
      determination. There are gender-specific differences in BMD measurements, and the
      rate of BMD changes with age and lifestyle. Previous studies have shown that the
      genetic loci underlying BMD variation are gender-specific in mice and humans. Our
      study aimed to investigate correlations between BMD at the spine, hip, and
      ultradistal radius (UD) and degree of shared genetic and environmental factors
      among them in females and males, separately. For a large sample of 4,489 subjects
      containing 2,667 females and 1,822 males from 512 Caucasian pedigrees, we
      performed bivariate variance decomposition analyses. Our results showed that the
      genetic correlations (rhoG), environmental correlations (rhoE), and phenotypical
      correlations (rhoP) were all significant and positive. Strong genetic
      correlations were observed in both female and male groups, ranging 0.590-0.738
      and 0.583-0.773, respectively. Genetic correlations of BMD at the spine, hip, and
      UD were generally higher than environmental correlations. In summary, we are the
      first to test the genetic and environmental correlations in females and males,
      separately. It is suggested that the phenotypic correlations of BMDs at the three
      different sites may have more genetic than environmental components. BMDs at the
      spine and hip may share more environmental components in females than males. We
      did not detect gender-specific difference in spine/UD and hip/UD. It is also
      indicated that the environmental factors that preserve or increase BMD at one
      skeletal site may have similar beneficial effects on some other skeletal sites
      and vice versa.

PMID- 16604286
TI  - Microfabricated discontinuous-edge surface topographies influence osteoblast
      adhesion, migration, cytoskeletal organization, and proliferation and enhance
      matrix and mineral deposition in vitro.
AB  - The fabrication of surfaces that stimulate increased adhesion, migration, and
      differentiated function of osteoblasts has been viewed as being desirable for
      many orthopedic applications. Previous studies have shown that microfabricated
      pits and grooves alter adhesion, spreading, matrix secretion, and production of
      mineral by rat calvarial osteoblasts (RCOs). The mechanisms underlying these
      effects are unknown, although microenvironment and cell alignment are considered
      to play a role. The aim of this work was to investigate the behavior of RCOs on
      microfabricated discontinuous-edge surfaces (DESs), which could provide an
      alternative means to control both the microenvironment and cellular alignment.
      Two types of discontinuous-type structures were employed, gap-cornered boxes and
      micron scale pillars. DES gap-cornered boxes and the pillars influenced the
      arrangement of F-actin, microtubules, and vinculin. Osteoblasts were guided in
      their direction of migration on both types of substrata. Both box DESs and
      pillars altered the staining intensity and localization pattern of
      phosphotyrosine and src-activated FAK localization. Cell multilayering, matrix
      deposition, and mineralization were enhanced on both discontinuous topographies
      when compared with smooth controls. This study shows that DESs alter adhesion,
      migration, and proliferative responses from osteoblasts at early time points (<1
      week) and promote multilayering, matrix deposition, and mineral deposition at
      later times (2-6 weeks). Such topographical patterns could potentially be
      employed as effective surface features on bone-contacting implants or in membrane
      based periodontal applications.

PMID- 16604287
TI  - Sprouty genes are expressed in osteoblasts and inhibit fibroblast growth factor
      mediated osteoblast responses.
AB  - Fibroblast growth factors (FGFs) and fibroblast growth factor receptors (FGFRs)
      are major regulators of skeletal growth and development. Signal transduction via
      FGFRs is complex and mediates proliferation, differentiation, or migration
      depending upon the cellular context. Members of the Spry gene family antagonize
      the FGFR signal transduction pathway and inhibit lung morphogenesis,
      angiogenesis, and chondrogenesis. We examined the expression of Spry2 in the
      osteoblastic MC3T3-E1 cell line. MC3T3-E1 cells express Spry2 in response to FGF1
      stimulation. Treatment of MC3T3-E1 cells with FGF1 results in the expression of
      Spry2 in a manner consistent with an early response gene. Pharmacological
      inhibitors of mitogen-activated protein kinase activation inhibit FGF1-induced
      expression of Spry2 mRNA. Transient overexpression of Spry2 in MC3T3-E1 resulted
      in decreased FGF1-mediated extracellular signal-regulated kinase phosphorylation
      and FGF1-stimulated osteopontin promoter activity. Furthermore, we show that
      Spry2 interacts with Raf-1 in a glutathione-S-transferase pulldown assay and that
      this interaction may involve multiple sites. Finally, Spry2 expression precedes
      the onset of the expression of osteoblast differentiation markers in an in vitro
      assay of primary osteoblast differentiation. Taken together, these results
      indicate that Spry2 expression is an early response to stimulation by FGF1 in
      MC3T3-E1 cells and acts as a feedback inhibitor of FGF1-induced osteoblast
      responses, possibly through interaction with Raf1.

PMID- 16604288
TI  - Endocytosis of tartrate-resistant acid phosphatase by osteoblast-like cells is
      followed by inactivation of the enzyme.
AB  - Tartrate-resistant acid phosphatase (TRACP) is generally used as a marker of
      osteoclasts. Yet, other bone-associated cells, such as osteoblasts and
      osteocytes, may also express activity of this enzyme. Osteoblasts containing
      TRACP activity are seen particularly in the vicinity of areas of bone resorption,
      suggesting that osteoclasts somehow induce TRACP activity in osteoblasts. In a
      recent study, we found that osteoblast-like cells appeared to have the capacity
      to endocytose TRACP released by osteoclast precursors. In the present study, we
      investigated the endocytosis of TRACP in more detail as well as the fate of the
      endocytosed enzyme. We found that incubation of osteoblast-like cells with TRACP
      coated beads resulted in attachment of a high number of beads to the cells. After
      culturing osteoblast-like cells with medium conditioned by blood monocytes that
      contain TRACP, activity of the enzyme was found in the cells. Following
      replacement of the medium by normal medium that did not contain TRACP, a decrease
      in the level of TRACP activity in osteoblast-like cells occurred. Our data
      strongly suggest that osteoblast-like cells recognize TRACP released by
      osteoclast precursors and that upon endocytosis inactivation of the enzyme
      occurs. We propose that uptake of the enzyme is important for the control of
      enzyme activity, thereby preventing degradation of matrix constituents.

PMID- 16604289
TI  - Single-nucleotide polymorphisms and haplotypes of bone morphogenetic protein
      genes and peripheral bone mineral density in young Korean men and women.
AB  - Bone morphogenetic proteins (BMPs) play critical roles in osteoblast
      differentiation. To investigate the association between common single-nucleotide
      polymorphisms (SNPs) of BMPs and bone mineral density (BMD), a cross-sectional
      study was conducted in healthy Korean men (n = 237) and women (n = 276) aged 20
      39 years. Calcaneus and distal radius BMD were measured by dual energy X-ray
      absorptiometry. SNPs of BMP2 (-1103C > A, c.584G > A, IVS1-2744A > G, c.893T >
      A), BMP4 (c.712T > C, IVS1-160C > T), and BMP6 (c.1283C > G, IVS4-6838A > G, IVS5
      + 24C > T) were determined using the 5'-nuclease assay. Significant associations
      were observed between BMP2 c.584G > A, c.893T > A genotypes and male calcaneus as
      well as female distal radius BMD. Men with the BMP2 c.893 AA genotype had a 16%
      higher BMD at the calcaneus (P for trend = 0.014), whereas women with this
      genotype had a 7% lower BMD at the distal radius than the other genotypes (P for
      trend = 0.010). A significant association was also observed between BMP4 IVS1
      160C > T and male calcaneus BMD (P for trend = 0.024). When the association
      between haplotypes and BMD was investigated, the AAGA haplotype of BMP2 was
      significantly associated with low bone mass in female distal radius (P for trend
      = 0.013). These results suggested that one or more SNPs of BMP2 and BMP4 are
      associated with peripheral BMD in Korean men and women. However, this association
      is dependent on anatomical sites and gender. Thus, larger studies with complete
      coverage of SNPs are needed in the future.

PMID- 16604290
TI  - 33rd European Symposium on Calcified Tissues, Prague, Czech Republic, 10-14 May
      2006. Abstracts.

PMID- 16604292
TI  - Measurement and characterization of whole-cell mechanical behavior.
AB  - An understanding of whole-cell mechanical behavior can provide insight into
      cellular responses to mechanical loading and diseases in which such responses are
      altered. However, this aspect of cellular mechanical behavior has received
      limited attention. In this study, we used the atomic force microscope (AFM) in
      conjunction with several mechanical characterization methods (Hertz contact
      theory, an exponential equation, and a parallel-spring recruitment model) to
      establish a mechanically rigorous method for measuring and characterizing whole
      cell mechanical behavior in the deformation range 0-500 nm. Using MC3T3-E1
      osteoblasts, measurement repeatability was assessed by performing multiple
      loading cycles on individual cells. Despite variability in measurements,
      repeatability of the measurement technique was statistically confirmed. The
      measurement technique also proved acceptable since only 5% of the total variance
      across all measurements was due to variations within measurements for a single
      cell. The parallel-spring recruitment model, a single-parameter model, accurately
      described the measured nonlinear force-deformation response (R2>0.99) while
      providing a mechanistic explanation of whole-cell mechanical behavior. Taken
      together, the results should improve the capabilities of the AFM to probe whole
      cell mechanical behavior. In addition, the success of the parallel-spring
      recruitment model provides insight into the micromechanical basis of whole-cell
      behavior.

PMID- 16604293
TI  - The effects of morphology, confluency, and phenotype on whole-cell mechanical
      behavior.
AB  - Emerging evidence indicates that cellular mechanical behavior can be altered by
      disease, drug treatment, and mechanical loading. To effectively investigate how
      disease and mechanical or biochemical treatments influence cellular mechanical
      behavior, it is imperative to determine the source of large inter-cell
      differences in whole-cell mechanical behavior within a single cell line. In this
      study, we used the atomic force microscope to investigate the effects of cell
      morphological parameters and confluency on whole-cell mechanical behavior for
      osteoblastic and fibroblastic cells. For nonconfluent cells, projected nucleus
      area, cell area, and cell aspect ratio were not correlated with mechanical
      behavior (p>or=0.46), as characterized by a parallel-spring recruitment model.
      However, measured force-deformation responses were statistically different
      between osteoblastic and fibroblastic cells (p<0.001) and between confluent and
      nonconfluent cells (p<0.001). Osteoblastic cells were 2.3-2.8 times stiffer than
      fibroblastic cells, and confluent cells were 1.5-1.8 times stiffer than
      nonconfluent cells. The results indicate that structural differences related to
      phenotype and confluency affect whole-cell mechanical behavior, while structural
      differences related to global morphology do not. This suggests that cytoskeleton
      structural parameters, such as filament density, filament crosslinking, and cell
      cell and cell-matrix attachments, dominate inter-cell variability in whole-cell
      mechanical behavior.

PMID- 16604294
TI  - Case report: homicide by a 10-year-old girl with autistic disorder.
AB  - This case study presents a 10-year-old girl with a diagnosis of Autistic
      Disorder, who killed her 6-month-old sister by throwing her out of a window. Her
      aggressive-impulsive behavior had a persistent pattern. She had a history of
      epilepsy, and was frequently exposed to physical abuse. She never attended a
      structured treatment program. Here, we discuss the possible risk factors
      including history of epilepsy, unsupervised-disorganized home environment,
      existence of physical abuse-neglect and lack of appropriate treatment program
      leading to violent behavior.

PMID- 16604296
TI  - The Babel effect: community linguistic diversity and extramarital sex in Uganda.
AB  - We examine the association of community linguistic diversity with non-spousal
      sexual activity in Uganda. We conducted a survey on rates of sexual contact in
      last 12 months among 1709 respondents age 18-60 living in Uganda in early 2001.
      Households were selected at random from Demographic and Health Survey (DHS) 2000
      household sampling frame listings in 12 districts and 120 clusters. Household
      listings described the principal language spoken by every household in the
      cluster. Sexual contact was reported by 26 vs. 13% of unmarried women in
      multilingual vs. monolingual clusters respectively. Extramarital sexual contact
      occurred for 29 vs. 16% for married men in multilingual vs. monolingual clusters
      respectively. These results were robust to multivariate models which included
      confounders such as urbanity, and cluster distance to market places, cinemas, and
      transportation. Our results suggest a robust association between residence in a
      multilinguistic community and higher rates of non-spousal sex.

PMID- 16604295
TI  - Impact of HIV-related stigma on health behaviors and psychological adjustment
      among HIV-positive men and women.
AB  - HIV-related stigmatization remains a potent stressor for HIV-positive people.
      This study examined the relationships among stigma-related experiences and
      depression, medication adherence, serostatus disclosure, and sexual risk among
      221 HIV-positive men and women. In bivariate analyses that controlled for
      background characteristics, stigma was associated with depressive symptoms,
      receiving recent psychiatric care, and greater HIV-related symptoms. Stigma was
      also associated with poorer adherence and more frequent serostatus disclosure to
      people other than sexual partners, but showed no association to sexual risk
      behavior. In a multivariate analysis that controlled for all correlates,
      depression, poor adherence, and serostatus disclosure remained as independent
      correlates of stigma-related experiences. Findings confirm that stigma is
      associated with psychological adjustment and adherence difficulties and is
      experienced more commonly among people who disclose their HIV status to a broad
      range of social contacts. Stigma should be addressed in stress management, health
      promotion, and medication adherence interventions for HIV-positive people.

PMID- 16604297
TI  - Perceptions about the acceptability of assessments of HIV medication adherence in
      Lilongwe, Malawi and Chennai, India.
AB  - Little research exists on acceptability issues related to assessments of
      adherence to ART in resource-poor settings. To help prepare for two large-scale,
      multisite ART intervention trials, this qualitative study of individuals in
      Chennai, India (49 men, 11 women; 33 taking ART, 27 not) and Lilongwe, Malawi (5
      men, 5 women, all taking ART) examined potential limitations of different types
      of adherence assessments: an adherence questionnaire, a pill diary, a pillbox, an
      electronic pill cap, and a medication punch card. Many participants reported that
      the various assessments would be acceptable. Potential limitations included
      issues surrounding literacy, the desire to appease one's medical provider,
      privacy and stigma, and "cheating." These potential limitations are similar to
      the limitations of these assessments in Western settings. However, the data
      highlight the need to consider individual patient level concerns when assessing
      ART adherence in different cultural settings. Innovative ways of monitoring
      adherence while maintaining standardization across sites are required in
      multisite trials.

PMID- 16604298
TI  - Osteoprotegerin and bone mineral density in hemodialysis patients.
AB  - INTRODUCTION: Osteoprotegerin is a soluble glycoprotein that belongs to the tumor
      necrosis-factor receptor superfamily. In vitro, osteoprotegerin blocks
      osteoclastogenesis in a dose-dependent manner. The serum osteoprotegerin level
      shows a positive correlation with bone metabolism markers and a negative
      correlation with bone mineral density in healthy persons, but these relationships
      are unclear in hemodialysis patients. We investigated the role of osteoprotegerin
      in bone loss in hemodialysis patients. METHODS: We measured baseline serum
      osteoprotegerin, bone metabolism markers, and bone mineral density in
      hemodialysis patients. A total of 201 patients (114 men and 87 women) were
      followed for 12 months, and bone mineral density was measured again to calculate
      the annual percent change in bone mineral density. Serum osteoprotegerin was also
      measured in 20 healthy persons. RESULTS: The osteoprotegerin levels of the
      hemodialysis patients were about three times higher than those of the healthy
      controls. The osteoprotegerin level showed a negative correlation with various
      bone metabolism markers. In multiple regression analysis, the annual percent
      change in bone mineral density showed a positive correlation with osteoprotegerin
      level, while there was a negative correlation with duration of hemodialysis and
      intact parathyroid hormone level. The osteoprotegerin levels of the hemodialysis
      patients were about three times higher than those of the healthy controls. The
      osteoprotegerin level showed a negative correlation with various bone metabolism
      markers. In multiple regression analysis, the annual percent change in bone
      mineral density showed a positive correlation with osteoprotegerin level, while
      there was a negative correlation with duration of hemodialysis and intact
      parathyroid hormone level. CONCLUSIONS: These correlations of osteoprotegerin are
      opposite to those found in healthy persons. However, osteoprotegerin might act to
      prevent bone loss even in hemodialysis patients.

PMID- 16604299
TI  - Evidence for specific phases in the development of human neuromelanin.
AB  - Neuromelanin is a dark-coloured pigment which forms in the dopamine neurons of
      the human midbrain. Here we describe the age-related development and regulation
      of neuromelanin within these dopamine neurons. 10 microm sections from formalin
      fixed midbrain from 29 people spanning the ages of 24 weeks to 95 years old were
      either stained with a basic Nissl substance stain (0.5% cresyl violet), or
      processed unstained. After locating the substantia nigra using the stained
      sections, digital photos were taken of individual ventral substantia nigra
      neurons in the unstained sections, and the cellular area occupied by pigment, and
      optical density were measured using computer software. These measurements
      demonstrated three developmental phases. Neuromelanin was not present at birth
      and initiation of pigmentation began at approximately 3 years of age, followed by
      a period of increasing pigment granule number and increasing pigment granule
      colouration until age 20. In middle and later life the colour of the pigment
      granules continued to darken but was not associated with any substantial growth
      in pigment volume. The identification of three phases and changes in the rate of
      neuromelanin production over time suggests the regulation of neuromelanin
      production and turnover, possibly through enzymatic processes.

PMID- 16604300
TI  - RGS4 genotype is not associated with antipsychotic medication response in
      schizophrenia.
AB  - The aims of the present study were to compare the allele frequencies of a common
      single nucleotide polymorphism located upstream of the regulator of G-protein
      signaling 4 (RGS4) gene (T > G, Rs 951436) in 219 Finnish patients with
      schizophrenia and in 389 control subjects, to analyze corresponding frequencies
      between two different subtypes of 93 schizophrenia patients according to their
      medication response, and to study the effect of this SNP on age at onset in
      schizophrenia. The RGS4 (T > G, Rs 951436) genotype was not associated with
      incidence or age at onset in schizophrenia. Neither was the RGS4 genotype
      associated with medication response with two different subpopulations with
      schizophrenia.

PMID- 16604301
TI  - An interaction between the serotonin transporter promoter region and dopamine
      transporter polymorphisms contributes to harm avoidance and reward dependence
      traits in normal healthy subjects.
AB  - There is evidence for an association between polymorphisms of serotonin- and
      dopamine-related genes and temperamental personality traits. Recent findings have
      shown that interactions between allelic variants of the different genes may
      contribute to personality traits. We examined the effects of serotonin
      transporter-linked promoter region (5-HTTLPR) and dopamine transporter (DAT1)
      gene polymorphisms for associations with the Temperament and Character Inventory
      (TCI) temperament subscales in 209 Koreans. We found that the variants of 5
      HTTLPR interacted with the DAT1 gene polymorphism to influence the HA and RD
      temperament subscales of TCI. Neither of these two genes affected any subscales
      of TCI alone.Controlling for the effects of gender and age, we found significant
      interactions between 5-HTTLPR and DAT1 genes on Harm Avoidance (HA) and Reward
      Dependence (RD) as measured by the TCI (Hotelling's Trace = 3.0, P = 0.02). In
      the presence of the DAT1 10/10 genotype, subjects of group L of 5-HTTLPR had a
      significantly higher HA score and significantly lower RD score than those of
      group S (F = 5.04, df = 1, p = 0.03 and F = 8.35, df = 1, p = 0.004,
      respectively). These findings suggest that the variants of 5-HTTLPR interacted
      with the DAT1 gene polymorphism to influence the HA and RD temperament subscales
      of TCI.

PMID- 16604302
TI  - Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat
      administration of levodopa/carbidopa with and without entacapone in patients with
      Parkinson's disease.
AB  - Addition of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN)
      prolongs plasma metabolism of levodopa (LD). Objectives were to determine the
      clinical response after EN addition and the plasma degradation of LD and 3-O
      methyldopa [3-OMD]. Not optimum treated hospitalised patients with Parkinson's
      disease received the same LD dosage on the first day only with carbidopa (CD) and
      on the second day with CD and EN (t.i.d.) within a standardised setting. We
      scored motor symptoms and measured LD- and 3-OMD levels on both days at fixed
      moments. Motor impairment significant better improved probably due to significant
      higher maximum concentrations [C(max)] and computed area under the curve values
      of LD levels during the LD/CD/EN condition. Time to C(max) of LD was
      significantly delayed after the first two LD/CD/EN intakes. An impact of EN on 3
      OMD levels appeared. A possibly augmented LD absorption and a prolonged LD
      metabolism after EN supplementation may contribute to a more continuous LD
      delivery to the brain.

PMID- 16604303
TI  - Polymorphic GGC repeat differentially regulates human reelin gene expression
      levels.
AB  - The human gene encoding Reelin (RELN), a pivotal protein in neurodevelopment,
      includes a polymorphic GGC repeat in its 5' untranslated region (UTR). CHO cells
      transfected with constructs encompassing the RELN 5'UTR with 4-to-13 GGC repeats
      upstream of the luciferase reporter gene show declining luciferase activity with
      increasing GGC repeat number (P < 0.005), as predicted by computer-based
      simulations. Conversely, RELN 5'UTR sequences boost reporter gene expression
      above control levels in neuronal SN56 and N2A cell lines, but 12- and 13-repeat
      alleles still yield 50-60% less luciferase activity compared to the more common 8
      and 10-repeat alleles (P < 0.0001). RELN "long" GGC alleles significantly blunt
      gene expression and may, through this effect, confer vulnerability to human
      disorders, such as schizophrenia and autism.

PMID- 16604304
TI  - Association study of polymorphisms in glycine transporter with schizophrenia.
AB  - Glycine acts as an obligatory co-agonist with glutamate on N-methyl-D-aspartate
      (NMDA) receptors. Brain glycine availability is determined by glycine
      transporters (GlyT1 or SLC6A9), which mediate glycine reuptake into nerve
      terminals. Since hypofunction of NMDA receptors has been implicated in the
      pathophysiology of schizophrenia, this study tests the hypothesis that GlyT1
      genetic variants confer susceptibility to schizophrenia. Four GlyT1 polymorphisms
      were studied in a sample population of 249 people with schizophrenia and 210
      normal controls. One polymorphism (rs16831541) was not informative in our Chinese
      population while the other three polymorphisms (rs1766967, rs2248632 and
      rs2248253) were analysed with chi-square tests and haplotype analysis.
      Significant linkage disequilibrium was obtained among the three polymorphisms.
      Neither single marker nor haplotype analysis revealed an association between
      variants at the GlyT1 locus and schizophrenia, suggesting that it is unlikely
      that the GlyT1 polymorphisms investigated play a substantial role in conferring
      susceptibility to schizophrenia in the Chinese population. Further studies with
      other GlyT1 variants, relating either to schizophrenia, psychotic symptoms or to
      therapeutic response in schizophrenia, are suggested.

PMID- 16604305
TI  - Possible association between nonsynonymous polymorphisms of the anaplastic
      lymphoma kinase (ALK) gene and schizophrenia in a Japanese population.
AB  - We examined, for the first time, the possible association between schizophrenia
      and the anaplastic lymphoma kinase (ALK) gene which plays an important role in
      neurodevelopment. When two nonsynonymous polymorphisms (Arg1491Lys and
      Glu1529Asp) were examined, there were significant differences in genotype and
      allele distributions between patients and controls. Individuals homozygous for
      the minor allele (1491Lys-1529Asp) were more common in patients than in controls
      (p = 0.0064, odds ratio 2.4, 95% CI 1.3-4.6). These results suggest that genetic
      variations of the ALK gene might confer susceptibility to schizophrenia.

PMID- 16604306
TI  - alpha-Synuclein promoter RsaI T-to-C polymorphism and the risk of Parkinson's
      disease.
AB  - Increased alpha-synuclein expression may be involved in the pathogenesis of
      Parkinson's disease (PD). We investigated the association of Rep1 microsatellite
      and RsaI T-to-C substitution in the alpha-synuclein promoter region with the risk
      of PD by a case-control study. The RsaI C/C genotype and C allele were found less
      frequently in PD patients than in controls. A reduced risk of the Rep1-RsaI 0-C
      haplotype (OR = 0.57, 95% CI = 0.36-0.90) with PD was evident. The quantitative
      real-time PCR study showed that the alpha-synuclein mRNA expression was increased
      (although not significantly) in PD patients with RsaI T/T genotype or Rep1-RsaI 0
      T haplotype as compared to T/C genotype or 0-C haplotype. Reporter constructs
      containing the RsaI C allele drove significantly lower transcriptional activity
      compared with the RsaI T allele in both IMR32 and 293 cells. The findings suggest
      that the RsaI T-to-C substitution may have a functional relevance to the
      susceptibility to PD.

PMID- 16604307
TI  - Comparison of spatial and temporal pattern for fMRI obtained with BOLD and
      arterial spin labeling.
AB  - Functional magnetic resonance imaging (fMRI) is presently either performed using
      blood oxygenation level-dependent (BOLD) contrast or using cerebral blood flow
      (CBF), measured with arterial spin labeling (ASL) technique. The present fMRI
      study aimed to provide practical hints to favour one method over the other. It
      involved three different acquisition methods during visual checkerboard
      stimulation on nine healthy subjects: 1) CBF contrast obtained from ASL, 2) BOLD
      contrast extracted from ASL and 3) BOLD contrast from Echo planar imaging.
      Previous findings were replicated; i) no differences between the three
      measurements were found in the location of the activated region; ii) differences
      were found in the temporal characteristics of the signals and iii) BOLD has
      significantly higher sensitivity than ASL perfusion. ASL fMRI was favoured when
      the investigation demands for perfusion and task related signal changes. BOLD
      fMRI is more suitable in conjunction with fast event related design.

PMID- 16604308
TI  - Screening for cognitive impairment in Parkinson's disease--which marker relates
      to disease severity?
AB  - The frequency and pattern of cognitive deficits in Parkinson's disease (PD) is
      under discussion. We assessed 157 consecutive subjects with PD (66.4 +/- 8.9
      years (mean +/- standard deviation); average duration of disease 3.5 +/- 1.3
      years; average Hoehn and Yahr stage 2.4 +/- 0.9) diagnosed in centers specialized
      for the diagnosis and treatment of PD with brief tests for memory (Memory
      Impairment Screen), attention (Letter Sorting Test) and semantic fluency
      (category animals). Impaired memory was observed in about one half of the
      subjects regardless of severity of disease as assessed by staging according to
      Hoehn and Yahr. With greater severity, free recall was impaired and subjects
      required the cues to recall the items. Performance in the Letter Sorting Test and
      the semantic fluency task declined with increasing Hoehn and Yahr stage, also. We
      conclude that cognitive deficits are frequent in PD. Further analyses reveal that
      even in selected screening tests (e.g. semantic fluency) a significant impairment
      with increasing disease severity (Hoehn and Yahr stage) as opposed to disease
      duration alone can be demonstrated.

PMID- 16604309
TI  - Frontal theta event-related synchronization: comparison of directed attention and
      working memory load effects.
AB  - Early studies showed that long-term encoding and retrieval of new information is
      associated with modulation of the theta rhythm. More recently, changes in theta
      power amplitude over frontal electrode sites were reported during working memory,
      yet their relative significance in regard to attentional and memory processes
      remains unclear. Event-related synchronisation responses in the 4-7.5 Hz theta
      EEG frequency band was studied in 12 normal subjects performing four different
      tasks: two working memory tasks in which load varied from one (1-back task) to
      two (2-back task) items, an oddball detection (attention) task and a passive
      fixation task. A phasic theta increase was observed following stimulus apparition
      on all electrode sites within each task, with longer culmination peak and maximal
      amplitude over frontal electrodes. Frontal theta event-related synchronization
      (ERS) was of higher amplitude in the 1-back, 2-back and detection tasks as
      compared to the passive fixation task. Additionally, the detection task elicited
      a larger frontal and central theta ERS than the 2-back task. By analyzing theta
      ERS characteristics in various experimental conditions, the present study reveals
      that early phasic theta response over frontal regions primarily reflects the
      activation of neural networks involved in allocation of attention related to
      target stimuli rather than working memory processes.

PMID- 16604310
TI  - Physiological and subjective responding to alcohol cue exposure in alcoholics and
      control subjects: evidence for appetitive responding.
AB  - 36 alcoholic patients, recruited from a treatment program, and 20 non-alcohol
      abusing control subjects were tested for their reactions to alcohol and non
      alcohol cues. The cue exposure paradigm included audio-visual (video), tactile,
      olfactory, and guided imagery cue components related to alcohol and non-alcohol
      beverages. Response measures were analyzed for significant difference based on
      alcohol and non-alcohol cue and patient type. Among the subjective ratings,
      alcohol cue specific increases in alcohol craving, desire to drink, alcohol-like
      high, positive drinking expectancies and alcohol-like withdrawal were seen in
      alcoholic subjects. Among the physiological measures, alcohol cue specific
      increases in salivation were seen in alcoholic subjects. Changes in heart rate,
      skin conductance and temperature were not specific to alcohol cues, or to
      alcoholic patients. The smelling of alcohol had the greatest impact on alcohol
      craving and skin conductance in alcoholic subjects. These findings demonstrate
      robust subjective effects, and weak physiological effects, in response to a
      multidimensional alcohol cue exposure paradigm. The response profile indicates
      cue reactivity in alcoholics as an appetitive based form of alcohol craving.

PMID- 16604311
TI  - Temporal uncertainty does not affect response latencies of movements produced
      during startle reactions.
AB  - Previous research has shown that a startle 'go' stimulus, presented at a constant
      latency with respect to a warning stimulus, is capable of eliciting an intended
      voluntary movement in a simple reaction time (RT) task at very short latencies
      without involvement of the cerebral cortex (Carlsen et al. in Exp Brain Res
      152:510-518, 2003; J Motor Behav 36:253-264, 2004a; Exp Brain Res 159:301-309
      2004b; Valls-Sole et al. in J Physiol 516:931-938, 1999). The purpose of the
      present experiment was to determine the effect of temporal uncertainty on
      response latency during an RT task that comprised a startle stimulus.
      Participants were required to perform an active 20 degrees wrist extension
      movement in response to an auditory tone that was presented 2,500 to 5,500 ms
      after a warning stimulus, in 1,000 ms increments. On certain trials the control
      auditory stimulus (80 dB) was unexpectedly replaced by the startle stimulus (124
      dB). When participants were startled the intended voluntary movement was
      initiated at approximately 70 ms, regardless of foreperiod duration. The
      magnitude and invariance of response latencies to the startle stimulus suggest
      that the intended movement had indeed been prepared prior to the arrival of the
      imperative go stimulus, within 2.5 s of the warning stimulus. Furthermore, there
      was no evidence that the prepared movement decayed over a period of at least 3 s.

PMID- 16604312
TI  - Anti-saccades away from faces: evidence for an influence of high-level visual
      processes on saccade programming.
AB  - The anti-saccade task is an important tool for investigating both the generation
      of voluntary saccades and the suppression of involuntary, stimulus driven,
      saccades. In the anti-saccade task participants have to suppress an involuntary
      saccade to the stimulus in order to generate a voluntary saccade away from the
      stimulus. The extent to which errors occur in this task indicates the ability of
      the stimulus to trigger an orienting response that is beyond the control of the
      participant. Here we show an increase in anti-saccade error rates away from an
      upright face compared to a non-upright face. This suggests that complex high
      level visual properties of the stimulus can influence whether involuntary
      orienting occurs.

PMID- 16604313
TI  - Visual angle is the critical variable mediating gain-related effects in manual
      control.
AB  - Theoretically visual gain has been identified as a control variable in models of
      isometric force. However, visual gain is typically confounded with visual angle
      and distance, and the relative contribution of visual gain, distance, and angle
      to the control of force remains unclear. This study manipulated visual gain,
      distance, and angle in three experiments to examine the visual information
      properties used to regulate the control of a constant level of isometric force.
      Young adults performed a flexion motion of the index finger of the dominant hand
      in 20 s trials under a range of parameter values of the three visual variables.
      The findings demonstrate that the amount and structure of the force fluctuations
      were organized around the variable of visual angle, rather than gain or distance.
      Furthermore, the amount and structure of the force fluctuations changed
      considerably up to 1 degrees , with little change higher than a 1 degrees visual
      angle. Visual angle is the critical informational variable for the visuomotor
      system during the control of isometric force.

PMID- 16604314
TI  - Activation of alpha2-adrenoreceptors suppresses the excitability of C1 spinal
      neurons having convergent inputs from tooth pulp and superior sagittal sinus in
      rats.
AB  - The aim of the present study was to test the hypothesis that activation of
      alpha(2)-adrenoreceptors modulates the excitability of C1 neurons having
      convergent inputs from both the tooth pulp (TP) and the superior sagittal sinus
      (SSS), by using the microiontophoretic techniques of drug application and
      immunohistochemical approaches. Extracellular single-unit recordings were made
      from 38 C1 neurons responding to electrical stimulation of TP under pentobarbital
      anesthetized rats. Seventy-one percent of C1 neurons (27/38) that responded to TP
      stimulation also responded to electrical stimulation of the SSS. In these
      neurons, L: -glutamate-evoked C1 neuronal discharge firings were increased in a
      dose-dependent manner. The mean glutamate-evoked firing rates were dose
      dependently inhibited after microiontophoretic application of clonidine (alpha(2)
      adrenoreceptor/imidazoline I(1) receptor agonist). The inhibition of glutamate
      evoked C1 mean firings by clonidine was antagonized by the co-application of
      idazoxan (alpha(2)-adrenoreceptor/imidazoline I(2) receptor antagonist),
      yohimbine (alpha(2)-adrenoreceptor) but not the alpha(1)-adrenoreceptor
      antagonist, prazosin with affinity for alpha(2B)- and alpha(2C)-adrenoreceptors.
      The mean spontaneous discharge frequencies were significantly inhibited by the
      microiontophoretic application of clonidine and this inhibition was reversed by
      the co-application of idazoxan, yohimbine. Microiontophoresis of clonidine also
      resulted in a reduction of TP-/SSS-evoked activity and this effect was reversed
      by the co-application of yohimbine. Immunoreactivity for alpha(2A)-adrenoreceptor
      was found in the superficial layers of I-III in the C1 region. These results
      suggest that alpha(2)-adrenoreceptor agonist clonidine inhibits the excitability
      of C1 neurons having convergent inputs from TP and SSS afferents, and that the
      activation of alpha(2A)-adrenoreceptors onto C1 dorsal horn neurons may
      contribute as a useful therapeutic target for the alleviation of trigeminal
      referred pain associated with migraine and tooth pain.

PMID- 16604315
TI  - Extensive training of elementary finger tapping movements changes the pattern of
      motor cortex excitability.
AB  - There is evidence of a strong capacity for functional and structural
      reorganization in the human motor system. However, past research has focused
      mainly on complex movement sequences over rather short training durations. In
      this study we investigated changes in corticospinal excitability associated with
      longer training of elementary, maximum-speed tapping movements. All participating
      subjects were consistent right-handers and were trained using either the right
      (experiment 1) or the left thumb (experiment 2). Transcranial magnetic
      stimulation was applied to obtain motor evoked potentials (MEPs) from the
      abductor pollicis brevis (APB) muscle of the right and the left hand before and
      after training. As a result of training, a significant increase was observed in
      tapping speed accompanied by increased MEPs, recorded from the trained APB
      muscle, following contralateral M1 stimulation. In the case of subdominant-hand
      training we additionally demonstrate increased MEP amplitudes evoked at the right
      APB (untrained hand) in the first training week. Enhanced corticospinal
      excitability associated with practice of elementary movements may constitute a
      necessary precursor for inducing plastic changes within the motor system. The
      involvement of the ipsilateral left M1 likely reflects the predominant role of
      the left M1 in the general control (modification) of simple motor parameters in
      right-handed subjects.

PMID- 16604316
TI  - Difference in the perception of the horizon during true and simulated tilt in the
      absence of semicircular canal cues.
AB  - Perception of tilt (somatogravic illusion) in response to sustained linear
      acceleration is generally attributed to the otolithic system which reflects
      either a translation of the head or a reorientation of the head with respect to
      gravity (tilt/translation ambiguity). The main aim of this study was to compare
      the tilt perception during prolonged static tilt and translation between 8 and 20
      degrees of tilt relative to the gravitoinertial forces (i.e., G and GIF,
      respectively) when the semicircular cues were no more available. An indirect
      measure of tilt perception was estimated by means of a visual and kinesthetic
      judgment of the gravitational horizon. The main results contrast with the
      interpretation regarding the tilt/translation ambiguity as the same orientation
      relative to the shear forces G for the true tilt or GIF in the centrifuge did not
      induce the same horizon perception. Visual adjustment and arm pointing in the
      centrifuge were always above the ones observed in a G environment. Part of the
      lowering of the judgment in the centrifuge may be related to the mechanical
      effect of GIF on the effectors as shown by the shift of the egocentric
      coordinates in the direction of GIF. The role of the extravestibular graviceptors
      in the judgment of the degree of tilt of one's own body relative to G or GIF was
      discussed.

PMID- 16604317
TI  - Inhibition of return in cue-target and target-target tasks.
AB  - Inhibition of return (IOR), the term given for the slowing of a response to a
      target that appeared at the same location as a previously presented stimulus, has
      been studied with both target-target (TT; participants respond to each successive
      event) and cue-target (CT; participants only respond to the second of two events)
      tasks. Although both tasks have been used to examine the processes and
      characteristics of IOR, few studies have been conducted to understand if there
      are any differences in the processes that underlie the IOR that results from
      ignoring (CT paradigm) or responding to (TT paradigm) the first stimulus. The
      purpose of the present study was to examine the notion that IOR found in TT tasks
      represents "true" IOR whereas IOR found in CT tasks consist of both "true" IOR
      and response inhibition (Coward et al. in Exp Brain Res 155:124-128, 2004).
      Consistent with the pattern of effects found by Coward et al. (Exp Brain Res
      155:124-128, 2004), IOR was larger in the CT task than in the TT task when a
      single detection response was required (Experiment 1). However, when participants
      completed one of two spatially-directed responses (rapid aiming movement to the
      location of the target stimulus), IOR effects from the CT and TT tasks were equal
      in magnitude (Experiment 2). Rather than CT tasks having an additional response
      inhibition component, these results suggest that TT tasks may show less of an
      inhibitory effect because of a facilitatory response repetition effect.

PMID- 16604318
TI  - Cortical short-term fatigue effects assessed via rhythmic brain-muscle coherence.
AB  - This study is aimed at assessing the short-term effects of muscular fatigue on
      the sensorimotor areas organization in the left and right hemispheres.
      Magnetoencephalographic (MEG) and electromyographic (EMG) activities were
      simultaneously recorded during the execution of a non-fatiguing motor task,
      performed before and after a task known to induce muscle fatigue (Fatigue).
      Coherence between cerebral and muscular rhythms as well as cerebral and muscular
      rhythms spectral densities were estimated during this non-fatiguing task and at
      rest. The MEG-EMG coherence in the beta band (13-32 Hz) was higher after than
      before Fatigue. The background activity reduction during contraction with respect
      to rest (i.e. the cerebral reactivity) was less evident after than before Fatigue
      in the gamma (33-45 Hz) and beta bands. When differentiating subjects on the base
      of Fatigue endurance times, while a huge inter-subject variability was found, an
      evident intra-subject similarity was observed for left and right arms, suggesting
      that resistance to fatigue is more an individual ability than a motor skill
      differentiated for the dominant and non-dominant side. In conclusion, signs of a
      more selective neural recruitment, more coupled with muscular activity, appeared
      as short-term effects of muscular fatigue in primary sensorimotor cortical areas.
      Evidence suggested that the reduction of cortical recruitment and the increased
      cortico-muscular coupling are distinct mechanisms.

PMID- 16604319
TI  - Eccentric eye and head positions in darkness induce deviation from the intended
      path.
AB  - Head and gaze are aligned with the actual path during locomotion. Before a turn
      is made, gaze changes in the direction of the planned trajectory. We investigated
      whether eccentric horizontal head and/or eye position without vision causes
      deviations from the intended straight path. Twenty blindfolded healthy volunteers
      were asked to walk toward a previously seen target 10 m straight ahead. Various
      combinations of head and eye positions were tested (eye-in-head gaze straight
      ahead or 35 degrees left or right with head straight ahead or 70 degrees left or
      right). Head rotation to the left caused a gait deviation to the right (3.7
      degrees ) and head rotation to the right caused a deviation to the left (2.7
      degrees ; F(2,40) = 34.966; P < 0.00001). Eye position also showed a tendency to
      cause gait deviations opposite in direction to gaze, which was, however, not
      significant. Deviations from the intended straight path were largest with head
      rotation and eyes straight ahead (gaze 70 degrees off target) or eyes opposite to
      head rotation (gaze 35 degrees off target). Notably, when lateral eye deviation
      added to head rotation (gaze 105 degrees off target), i.e., gaze is directed
      backward, mean deviations decreased (2.3 degrees to the right and 1.2 degrees to
      the left). Thus, we show that (1) eccentric head positions induce direction
      specific gait deviations that are independent of concurrent environmental visual
      information, and (2) that gait deviations are contraversive to eye-head gaze
      rather than ipsiversive as reported by others for visually controlled locomotion.
      The direction of deviation may reflect the compensation of an expected or
      perceived deviation in the direction of gaze.

PMID- 16604320
TI  - There are differences in cerebral activation between females in distinct
      menstrual phases during viewing of erotic stimuli: A fMRI study.
AB  - There is evidence that men experience more sexual arousal than women but also
      that women in mid-luteal phase experience more sexual arousal than women outside
      this phase. Recently, a few functional brain imaging studies have tackled the
      issue of gender differences as pertaining to reactions to erotica. The question
      of whether or not gender differences in reactions to erotica are maintained with
      women in different phases has not yet been answered from a functional brain
      imaging perspective. In order to examine this issue, functional MRI was performed
      in 22 male and 22 female volunteers. Subjects viewed erotic film excerpts
      alternating with emotionally neutral excerpts in a standard block-design
      paradigm. Arousal to erotic stimuli was evaluated using standard rating scales
      after scanning. Two-sample t-test with uncorrected P < 0.001 values for a priori
      determined region of interests involved in processing of erotic stimuli and with
      corrected P < 0.05 revealed gender differences: Comparing women in mid-luteal
      phase and during their menses, superior activation was revealed for women in mid
      luteal phase in the anterior cingulate, left insula, and orbitofrontal cortex. A
      superior activation for men was found in the left thalamus, the bilateral
      amygdala, the anterior cingulate, the bilateral orbitofrontal, bilateral
      parahippocampal, and insular regions, which were maintained at a corrected P in
      the amygdala, the insula, and thalamus. There were no areas of significant
      superior activation for women neither in mid-luteal phase nor during their
      menses. Our results indicate that there are differences between women in the two
      cycle times in cerebral activity during viewing of erotic stimuli. Furthermore,
      gender differences with women in mid-luteal phases are similar to those in
      females outside the mid-luteal phase.

PMID- 16604321
TI  - The effects of vitamin E on penicillin-induced epileptiform activity in rats.
AB  - Epilepsy is a disorder characterized by recurrent seizures, which can increase
      the content of reactive oxygen in the brain. Active oxygen free radical
      scavengers such as ascorbic acid or alpha-tocopherol (vitamin E) might prevent
      epilepsy. A variety of animal seizure models exist which help to document the
      effects of vitamin E and specify its action. In this study, we have evaluated
      dose-dependent effect of alpha-tocopherol on penicillin-induced epileptiform
      activity, analyzed by electrocorticogram (ECoG). The epileptiform activity was
      induced by microinjection of penicillin into the left sensorimotor cortex. Thirty
      minutes after penicillin injection, 100, 300, or 500 mg/kg of alpha-tocopherol
      was administrated intramuscularly (i.m.). alpha-Tocopherol (100, 300, or 500
      mg/kg) alone did not significantly change the spike amplitudes in non-penicillin
      pretreated control animals. alpha-Tocopherol of 300, or 500 mg/kg significantly
      decreased the frequency of epileptiform activity in the penicillin-pretreated
      animals. The low dose of alpha-tocopherol (100 mg/kg) did not significantly
      change either amplitude or frequency of epileptiform activity. alpha-Tocopherol
      of 500 mg/kg i.m. was the most effective dose in changing of frequency on
      penicillin-induced epileptiform activity. The anti-convulsant effects of alpha
      tocopherol appeared 80, 60, 30 min after alpha-tocopherol injection in 300, 500,
      and 3 day vitamin E supplemented groups. These data indicate that alpha
      tocopherol decreases the frequency of penicillin-induced epileptic activity.

PMID- 16604322
TI  - Is the body-coil at 3 Tesla feasible for the MRI evaluation of the painful knee?
      A comparative study.
AB  - The purpose of this study was to compare the in-built body coil of the 3.0-Tesla
      (T) scanner with a dedicated surface coil of a 1.5 T system regarding knee
      imaging. We performed an intraindividual prospective clinical trial on 17
      patients with knee pain using magnetic resonance imaging (MRI) at 1.5 and 3.0 T
      systems equipped with identical gradient systems. Proton-density-weighted turbo
      spin echo sequences with the same spatial resolution and comparable contrast
      parameters were used. A quantitative measurement of signal to noise ratio (SNR),
      relative contrast (RC) and contrast to noise ratio (CNR) between muscle and bone
      marrow was performed, followed by a qualitative assessment of anatomic/pathologic
      structures and the extent of artefacts. At 3.0 T, 30 lesions (91%) compared to 33
      lesions at 1.5 T were detected. The SNR/CNR/RC were moderately reduced at 3.0 T
      versus 1.5 T (muscle 42 vs 47 and bone 83 vs 112/46 vs 69/0.33 vs 0.43). Motion
      artefacts from the pulsating popliteal artery were significantly increased at 3.0
      T. A visible and measurable signal loss occurred at 3.0 T using the built-in body
      coil compared with the dedicated 1.5 T knee coil, but nearly all clinically
      important information could be obtained.

PMID- 16604323
TI  - Quantitative assessment of selective in-plane shielding of tissues in computed
      tomography through evaluation of absorbed dose and image quality.
AB  - This study aimed at assessment of efficacy of selective in-plane shielding in
      adults by quantitative evaluation of the achieved dose reduction and image
      quality. Commercially available accessories for in-plane shielding of the eye
      lens, thyroid and breast, and an anthropomorphic phantom were used for the
      evaluation of absorbed dose and image quality. Organ dose and total energy
      imparted were assessed by means of a Monte Carlo technique taking into account
      tube voltage, tube current, and scanner type. Image quality was quantified as
      noise in soft tissue. Application of the lens shield reduced dose to the lens by
      27% and to the brain by 1%. The thyroid shield reduced thyroid dose by 26%; the
      breast shield reduced dose to the breasts by 30% and to the lungs by 15%. Total
      energy imparted (unshielded/shielded) was 88/86 mJ for computed tomography (CT)
      brain, 64/60 mJ for CT cervical spine, and 289/260 mJ for CT chest scanning. An
      increase in image noise could be observed in the ranges were bismuth shielding
      was applied. The observed reduction of organ dose and total energy imparted could
      be achieved more efficiently by a reduction of tube current. The application of
      in-plane selective shielding is therefore discouraged.

PMID- 16604325
TI  - [E-learning in the education and training of physicians. Methods, results,
      evaluation].
AB  - E-learning has been established in the education and training of physicians in
      various types: linear sequential and hyper-textual forms of multimedia
      presentations and texts, tutorial systems and simulations. Case-based e-learning
      systems are of special importance in medicine because they allow for mediation of
      process and practical knowledge by presentation of authentic medical cases in a
      simulated environment. The integration into the medical education and advanced
      professional training is crucial for the long-term success of e-learning; in case
      based systems this can be accomplished by blended learning approaches which
      combine elements of traditional teaching with e-learning. Learning management
      systems (LMS) support integration of traditional teaching and e-learning by
      serving as an organizational platform for content of teaching. Further, they
      provide means of communication for trainers and trainees, authoring tools,
      interactive components, course management and role-based sharing concept. The
      dissemination of e-learning can be fostered by attention to requirements and user
      analysis, early adoption to organizational structures, curricular integration and
      continuous cooperation with students. Summarized, didactic and organizational
      aspects determine the success of our own e-learning offers as well as they
      influence the general further development of e-learning more than technical
      features.

PMID- 16604326
TI  - [The system of continuing professional education of medical doctors in Austria.
      Structure, guidelines and quality management].
AB  - This article describes the system of continuing medical education in Austria.
      Pursuant to section sign 49 para.1* of the Austrian Medical Law 1998/Amendment
      2001, Austrian doctors are under the obligation to participate in continuing
      professional education according to the guidelines of the Austrian Medical
      Chamber. The Austrian doctors see themselves as members of an independent
      profession. The Austrian system of continuing (physician) professional education
      developed continuously, for one, based on the principle of self-responsibility of
      licensed doctors and for the other, on the responsibility for self-administration
      of the medical profession. The participation in CPD or CME events, which are
      quality assured by a given set of rules, is documented by a time-limited diploma
      issued by the Austrian Medical Chamber. The recognition system comprises CPD-CME
      events in Austria as well as abroad, literature study under specific rules
      including an assessment system and the use of electronic media. The CPD-CME
      guidelines are updated annually by the Austrian Medical Chamber. The permanent
      maintenance and administration of the CPD-CME Programme of the Austrian Medical
      Chamber (Diplom-Fortbildungs-Programm, DFP), was handed over to the Austrian
      Academy of Physicians, which is under the obligation to report to its founding
      body, the Austrian Medical Chamber.

PMID- 16604327
TI  - [Online continuing medical education based on national disease management
      guidelines. The e-learning platform leitlinien-wissen.de].
AB  - Effective translation of relevant knowledge into clinical practice is essential
      for modern health care systems. National Disease Management Guidelines (NDMG) are
      considered relevant instruments to support this transfer. To implement NDMG
      Internet-based continuing medical education (CME), modules and online case-based
      learning objects were designed and published. To ensure high quality the contents
      are based on NDMG and subjected to multi-step review processes. Presentation on
      the web was realized through a modified content management system. To obtain a
      CME certificate, completing an online questionnaire using a four-point Likert
      scale was mandatory. Between June 2003 and April 2005, 3,105 physicians were
      registered and used the platform: 95% of the physicians expressed positive
      feedback in the evaluation questionnaire, and 35% actually used the corresponding
      NDMG in practice. This prompted the development of interactive medical case-based
      learning objects as a second learning pathway. An Internet platform for CME
      including case-based learning objects can be a helpful tool to assure the
      provision of scientific knowledge for patient care.

PMID- 16604329
TI  - [Quantitative determination of thermosensitivity after mandibular sagittal split
      osteotomy].
AB  - BACKGROUND: To determine the temperature- and pain thresholds of patients (n=20)
      who had undergone mandibular sagittal split osteotomy (MSSO), we developed a
      specific thermal probe to evaluate the neurosensory disturbances of the inferior
      alveolar nerve under prospective study conditions. METHODS: Measurements were
      performed prior to surgery and postoperatively up to 6 months. Thermal probe test
      results were compared to the results of the usual two-point discrimination test
      and the sharp/blunt test. Furthermore we took the subjective neurosensory
      perception of each patient into account. RESULTS: With focus on our newly
      developed thermal probe and under comparison with the preoperative results, the
      postoperative neurosensory tests revealed increased thresholds of up to 12.7
      degrees C. Between 3 and 6 months postoperatively, quantitative resensitization
      could be evaluated. In contrast, the usual testing methods were not accurate
      enough to give valuable significant data within 3 and 6 months postoperatively.
      Our evaluation could also show that after 6 months thermal thresholds were up 1.5
      degrees C as compared with the preoperative status. CONCLUSION: Base on our data
      we conclude that the newly developed thermal probe is accurate to determine
      neurosensory disturbances of the alveolar inferior nerve after sagittal split
      osteotomy. As compared with the more common testing methods, an advantage of our
      contemporary measurement device is the quantitative analysis of nerval function.

PMID- 16604328
TI  - [Osteosynthesis in facial bones: silicon nitride ceramic as material].
AB  - BACKGROUND: The favorable properties of silicon nitride (Si3N4) ceramic, such as
      high stability and biocompatibility suggest its biomedical use as an implant
      material. The aim of this study was to test its suitability for osteosynthesis.
      MATERIALS AND METHODS: A Si3N4 prototype minifixation system was manufactured and
      implanted for osteosynthesis of artificial frontal bone defects in three
      minipigs. After 3 months, histological sections, CT and MRI scans were obtained.
      Finite element modeling (FEM) was used to simulate stresses and strains on Si3N4
      miniplates and screws to calculate survival probabilities. RESULTS: Si3N4
      miniplates and screws showed satisfactory intraoperative workability. There was
      no implant loss, displacement or fracture. Bone healing was complete in all
      animals and formation of new bone was observed in direct contact to the implants.
      CONCLUSIONS: Si3N4 ceramic showed a good biocompatibility outcome both in vitro
      and in vivo. This ceramic may serve as biomaterial for osteosynthesis, e.g. of
      the midface including reconstruction of the floor of the orbit and the skull
      base. Advantages compared to titanium are no risk of implantation to bone with
      mucosal attachment, no need for explantation, no interference with radiological
      imaging.

PMID- 16604330
TI  - [Organ-preserving treatment in inoperable patients with primary oral and
      oropharyngeal carcinoma: chances and limitations].
AB  - INTRODUCTION: The aim of this study was to demonstrate the chances of
      nonoperative therapy in those patients from an unselected population suffering
      from primary previously untreated squamous cell carcinomas of the oral cavity and
      the oropharynx who did not seem to be operable. PATIENTS AND METHODS: Following
      interdisciplinary counseling and extensive individual discussion, 72 (21%) of 340
      consecutive patients (1997-2004) did not or did not reasonably seem to be
      operable; three other patients with stage II disease refused surgery. Of the
      inoperable patients, 95%suffered from far-advanced stage IV disease, 8% had
      distant metastases, 14% had synchronous malignancies, 9% were aged over 85 years
      combined with advanced malignant disease, and nearly 50% were limited in their
      activity or were even bedridden. Depending on fitness and tumor extent, three
      therapy regimens were used: intra-arterial (i.a.) high-dose chemotherapy with
      systemic antagonization for palliation, induction with this i.a. high-dose
      chemotherapy followed by additional radiotherapy, and induction with the i.a.
      high-dose chemotherapy followed by additional radiochemotherapy. RESULTS: Thirty
      two patients were treated with i.a. chemotherapy alone for palliation with few
      acute side effects. The response rate was 34%, and a further growth of the tumour
      could be inhibited in 49%. The 1- and 2-year survival rates were 21 and 14%,
      respectively. The three patients who refused surgery experienced complete
      clinical remission and survived 8, 6, and 2 years, respectively, to date. Twenty
      three patients were fit enough to receive additional radiotherapy, and 17 an
      additional radiochemotherapy. Of the patients, 22% had to cut short additional
      radiotherapy and 47% had to discontinue concomitant chemotherapy. The 1- and 2
      year survival rates were 41 and 25%, respectively; 14 of these irradiated
      patients experienced long-lasting complete clinical remission >2 years.
      CONCLUSION: About 20% of the patients classified as inoperable could achieve long
      lasting remission. Viewed with caution, sex (male), performance state (ECOG) <3,
      and positive response to i.a. chemotherapy could be regarded as predictors for
      therapeutic success. The combination of i.a. chemotherapy and radiochemotherapy
      seemed to be most successful. Conversely, the therapies offered could not achieve
      a substantial improvement of survival in 80% of patients classified as
      inoperable; the most successful therapy combination could be offered to merely
      23% of patients as classified inoperable due to reduced general condition. The
      i.a. high-dose chemotherapy has to be regarded as a well tolerated and effective
      palliation. This descriptive analysis must be followed by specific studies to
      establish clinical treatment recommendations.

PMID- 16604331
TI  - Clinical quiz: mycotic aneurysm of the right common iliac artery.

PMID- 16604334
TI  - Effects of clay turbidity and density of pikeperch (Sander lucioperca) larvae on
      predation by perch (Perca fluviatilis).
AB  - Increased turbidity reduces visibility in the water column, which can negatively
      affect vision-oriented fish and their ability to detect prey. Young fish could
      consequently benefit from high turbidity levels that can provide a protective
      cover, reducing predation pressure. Perch (Perca fluviatilis) are commonly found
      in littoral zones of temperate lakes and coastal areas of the Baltic Sea.
      Pikeperch (Sander lucioperca) spawn in these areas, so perch is a potential
      predator for pikeperch larvae. We conducted laboratory experiments to test the
      predation of perch on pikeperch larvae at different turbidity levels (5-85
      nephelometric turbidity units), densities of pikeperch larvae (2-21 individuals
      l(-1)) and volumes of water (10-45 l). The logistic regression showed that the
      probability of larvae eaten depended significantly on turbidity and volume of
      water in the bags, while density of larvae was not significant. However, because
      container size is known to affect predation, the data was divided into two groups
      based on water volume (10-20 and 25-45 l) to reduce the effects of container
      size. In either group, probability of predation did not significantly depend on
      volume, whereas turbidity was significant in both groups, while density was
      significant in larger water volumes. Thus, high turbidity impaired perch
      predation and protected pikeperch larvae from perch predation. Because density of
      larvae was also a significant factor affecting predation of perch, the dispersal
      of pikeperch larvae from spawning areas should also increase the survival of
      larvae.

PMID- 16604333
TI  - SGK1-dependent cardiac CTGF formation and fibrosis following DOCA treatment.
AB  - The mineralocorticoids aldosterone and deoxycorticosterone acetate (DOCA)
      stimulate renal tubular salt reabsorption, increase salt appetite, induce
      extracellular volume expansion, and elevate blood pressure. Cardiac effects of
      mineralocorticoids include stimulation of matrix protein deposition leading to
      cardiac fibrosis, which is at least partially due to the direct action of the
      hormones on cardiac cells. The signaling mechanisms mediating mineralocorticoid
      induced cardiac fibrosis have so far remained elusive. Mineralocorticoids have
      been shown to upregulate the serum- and glucocorticoid-inducible kinase 1 (SGK1),
      which participates in the effects of mineralocorticoids on renal tubular Na+
      reabsorption and salt appetite. To explore the involvement of SGK1 in the
      pathogenesis of mineralocorticoid-induced cardiac fibrosis, SGK1 knockout mice
      (sgk1-/-) and wild-type littermates (sgk1+/+) were implanted a 21-day-release 50
      mg DOCA pellet and supplied with 1% NaCl in drinking water for 18 days. This
      DOCA/high-salt treatment increased blood pressure in both genotypes but led to
      significant cardiac fibrosis only in sgk1+/+ but not in sgk1-/- mice. According
      to real-time polymerase chain reaction and Western blotting, DOCA/high-salt
      treatment enhanced transcript levels and protein expression of cardiac connective
      tissue growth factor (CTGF) only in sgk1+/+ but not in sgk1-/- mice. Furthermore,
      DOCA (10 microM) upregulated CTGF expression and enhanced CTGF promoter activity
      in lung fibroblasts isolated from sgk1+/+ but not from sgk1-/- mice, an effect
      involving spironolactone-sensitive mineralocorticoid receptors and activation of
      nuclear factor-kappaB (NFkappaB). Our results suggest that SGK1 plays a decisive
      role in mineralocorticoid-induced CTGF expression and cardiac fibrosis.

PMID- 16604335
TI  - Dietary characterization of the hominoid Khoratpithecus (Miocene of Thailand):
      evidence from dental topographic and microwear texture analyses.
AB  - The genus Khoratpithecus, a hominoid thought to be related to the orangutan
      lineage, is represented by two known fossil species K. chiangmuanensis and K.
      piriyai. Both were discovered in Southeast Asia (Thailand) and are dated to the
      Middle and Late Miocene, respectively. In this study, dental topographic and
      microwear texture analyses were used to examine molars from both of these
      species, with the goal of understanding their dietary preferences. Although
      sample sizes are small for Khoratpithecus, available data are compared to that
      collected for extant apes. Environmental evidence, such as botanical remains and
      sedimentological data, is also considered for comparisons with dietary
      reconstruction. Results from dental topographic analysis suggest that the two
      fossil species were better adapted to a diet of fruits than to one of leaves,
      much like the living orangutan or chimpanzee. Results from microwear texture
      analysis further support this, suggesting that Khoratpithecus preferred soft
      fruits to hard fruits or seeds. And finally, the botanical and sedimentological
      evidence point to environments for Khoratpithecus that would have been compatible
      with a fruit-eating species. Given the small sample sizes available for analysis,
      however, definitive judgments are not yet possible at this time.

PMID- 16604336
TI  - Introgression of genomic components from Chinese Brassica rapa contributes to
      widening the genetic diversity in rapeseed (B. napus L.), with emphasis on the
      evolution of Chinese rapeseed.
AB  - In spite of its short history of being an oil crop in China, the Chinese semi
      winter rapeseed (Brassica napus L., 2n = 38, AACC) has been improved rapidly by
      intentional introgression of genomic components from Chinese B. rapa (2n = 20,
      AA). As a result, the Chinese semi-winter rapeseed has diversified genetically
      from the spring and winter rapeseed grown in the other regions such as Europe and
      North America. The objectives of this study were to investigate the roles of the
      introgression of the genomic components from the Chinese B. rapa in widening the
      genetic diversity of rapeseed and to verify the role of this introgression in the
      evolution of the Chinese rapeseed. Ten lines of the new type of rapeseed, which
      were produced by introgression of Chinese B. rapa to Chinese normal rapeseed,
      were compared for genetic diversity using amplified fragment length polymorphism
      (AFLP) with three groups of 35 lines of the normal rapeseed, including 9 semi
      winter rapeseed lines from China, 9 winter rapeseed lines from Europe and 17
      spring rapeseed lines from Northern Europe, Canada and Australia. Analysis of 799
      polymorphic fragments revealed that within the groups, the new type rapeseed had
      the highest genetic diversity, followed by the semi-winter normal rapeseed from
      China. Spring and winter rapeseed had the lowest genetic diversity. Among the
      groups, the new type rapeseed group had the largest average genetic distance to
      the other three groups. Principal component analysis and cluster analysis,
      however, could not separate the new type rapeseed group from Chinese normal
      rapeseed group. Our data suggested that the introgression of Chinese B. rapa
      could significantly diversify the genetic basis of the rapeseed and play an
      important role in the evolution of Chinese rapeseed. The use of new genetic
      variation for the exploitation of heterosis in Brassica hybrid breeding is
      discussed.

PMID- 16604332
TI  - Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy.
AB  - Excessive body iron or iron overload occurs under conditions such as primary
      (hereditary) hemochromatosis and secondary iron overload (hemosiderosis), which
      are reaching epidemic levels worldwide. Primary hemochromatosis is the most
      common genetic disorder with an allele frequency greater than 10% in individuals
      of European ancestry, while hemosiderosis is less common but associated with a
      much higher morbidity and mortality. Iron overload leads to iron deposition in
      many tissues especially the liver, brain, heart and endocrine tissues. Elevated
      cardiac iron leads to diastolic dysfunction, arrhythmias and dilated
      cardiomyopathy, and is the primary determinant of survival in patients with
      secondary iron overload as well as a leading cause of morbidity and mortality in
      primary hemochromatosis patients. In addition, iron-induced cardiac injury plays
      a role in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion
      injury, Friedreich ataxia and neurodegenerative diseases. Patients with iron
      overload also routinely suffer from a range of endocrinopathies, including
      diabetes mellitus and anterior pituitary dysfunction. Despite clear connections
      between elevated iron and clinical disease, iron transport remains poorly
      understood. While low-capacity divalent metal and transferrin-bound transporters
      are critical under normal physiological conditions, L-type Ca2+ channels (LTCC)
      are high-capacity pathways of ferrous iron (Fe2+) uptake into cardiomyocytes
      especially under iron overload conditions. Fe2+ uptake through L-type Ca2+
      channels may also be crucial in other excitable cells such as pancreatic beta
      cells, anterior pituitary cells and neurons. Consequently, LTCC blockers
      represent a potential new therapy to reduce the toxic effects of excess iron.

PMID- 16604337
TI  - Construction of a watermelon BAC library and identification of SSRs anchored to
      melon or Arabidopsis genomes.
AB  - A bacterial artificial chromosome (BAC) library was constructed for watermelon
      (Citrullus lanatus (Thunb.) Matsum. & Nakai var. lanatus) with an average insert
      size of 106 kb, providing 21 haploid genome equivalents. The library was used to
      identify BAC clones that are anchored to probes evenly distributed on the genomes
      of melon or Arabidopsis. Twenty eight probes (representing 66% of the tested
      probes) from melon and 30 probes (65%) from Arabidopsis identified positive BAC
      clones. Two methods were implemented to identify SSRs from the positively
      hybridizing BAC clones. First, analysis of BAC end sequences revealed 37 SSRs.
      For the second method, pooled DNA of BACs identified by the melon probes was used
      to develop a shotgun library. The library was then screened with synthetic SSR
      oligonucleotides by hybridization. Sequence analysis of positively hybridizing
      shotgun clones revealed 142 different SSRs. Thirty eight SSRs were characterized
      using three watermelon cultivars, five plant introduction (PI) accessions of C.
      lanatus var lanatus and four PIs of C. lanatus var citroides. Of these, 36 (95%)
      were found to be polymorphic with up to six alleles per marker. Polymorphism
      information content values for polymorphic markers varied between 0.22 and 0.79
      with an average of 0.53. The methods described herein will be valuable for the
      construction of a watermelon linkage map with SSRs evenly distributed on its
      genome that is anchored to the genomes of melon and Arabidopsis.

PMID- 16604338
TI  - Toxicokinetics of bisphenol A in pregnant DA/Han rats after single i.v.
      application.
AB  - Bisphenol A (BPA) is an important chemical in the production of epoxy resins and
      polycarbonate plastics, and basic monomers which are used for a variety of
      applications. Consumer exposure to BPA may be possible from migration of BPA from
      dental sealants or from polycarbonate or epoxy-lined food and drink containers.
      BPA is known to act as weak estrogen mimic in rodents, and there is a concern of
      adverse endocrine effects, especially from prenatal exposure to this potential
      'endocrine disruptor'. To address this concern, we have studied the disposition
      and transplacental transfer of BPA in pregnant DA/Han rats on day 18 of
      gestation. The BPA concentrations were determined by GC/MS analysis in maternal
      blood, maternal organs (liver, kidney, uterus), placenta and fetuses (fetal liver
      and residual tissues) at different time-points (5-360 min) after intravenous
      administration of 10 mg BPA/kg body weight. Total BPA (aglycone and conjugates)
      was analyzed in all tissue samples after enzymatic hydrolysis and liquid/liquid
      extraction; in maternal plasma, total BPA and BPA aglycone were analyzed in
      parallel samples (with/without hydrolysis). Soon (5 min) after the i.v. injection
      a mean total BPA concentration of 3.8 microg/ml was found in maternal plasma; it
      declined in the first 2 h to 0.7 microg/ml. Early after injection, the majority
      of circulating BPA (almost 80%) was still in the aglycone form, but, metabolism
      by phase II enzymes decreased the BPA aglycone concentration to 0.3 microg/ml
      after 2 h. Despite this efficient conjugation, BPA was rapidly distributed in the
      organism: In well perfused organs peak concentrations for total BPA were attained
      20-30 min after intravenous administration, with mean values of about 9.7
      microg/g in maternal liver, 8.6 microg/g in kidneys, and 6.2 microg/g in the
      uterus. The peak values in other tissues were lower, with 4.0 microg/g for
      placenta, 3.3 microg/g for fetal liver, and 2.4 microg/g for residual fetus
      homogenate. The BPA levels in all tissues thereafter declined more or less in
      parallel with those in maternal blood. The rather similar concentration time
      course in placenta and fetal liver indicates that BPA is readily transferred
      across the placenta of DA/Han rats to the fetus. Our data on BPA disposition in
      DA/Han rats are discussed in the context of other kinetic studies with BPA in
      pregnant rats, and in relation to the previous results from our laboratory (Degen
      et al. Arch Toxicol 76:23-29, 2002a, b, c) demonstrating comparable
      transplacental transfer of daidzein, a phytoestrogen that accounts for a
      significant portion of total human exposure to potential endocrine disruptors.

PMID- 16604342
TI  - Adsorptive stripping voltammetric determination of netilmicin in the presence of
      formaldehyde.
AB  - A linear sweep adsorptive stripping voltammetric method for the determination of
      netilmicin in the presence of formaldehyde has been proposed for the first time.
      In the presence of 3.0 x 10(-3) g ml(-1) formaldehyde, netilmicin exhibits a
      sensitive cathodic peak at -1.30 V (vs. the saturated calomel electrode, SCE) in
      a medium of Britton-Robinson buffer (pH 8.7) with a scan rate of 100 mV s(-1)
      after a preconcentration period of 120 s at -1.10 V (vs. SCE). The peak current
      showed a linear dependence on the netilmicin concentration over the range 4.2 x
      10(-9)-1.0 x 10(-7) g ml(-1). The achieved limits of detection and quantitation
      were 1.0 x 10(-10) and 3.3 x 10(-10) g ml(-1) netilmicin, respectively. It was
      deduced from the experiments that the amine-aldehyde condensation product formed
      between netilmicin and formaldehyde is mainly responsible for the appearance of
      the peak. The electrochemical behavior of netilmicin in the presence of
      formaldehyde has been studied. The method was applied to the direct determination
      of netilmicin in injectable formulations and spiked human urine and serum
      samples.

PMID- 16604339
TI  - Isobolographic analysis of interactions between loreclezole and conventional
      antiepileptic drugs in the mouse maximal electroshock-induced seizure model.
AB  - This study examined the interaction characteristics between loreclezole (LCZ) and
      various conventional antiepileptic drugs (phenytoin--PHT, carbamazepine--CBZ,
      valproate--VPA and phenobarbital--PB) in the mouse maximal electroshock (MES)
      induced seizure model using isobolographic analysis. Drug-related adverse effects
      were ascertained by use of the chimney test (motor impairment) and the step
      through passive avoidance task (learning and retrieval). It was observed that the
      combination of LCZ with VPA or PB, at the fixed ratio of 1:1, was supra-additive
      (synergistic) and the combination of LCZ with CBZ, at all fixed ratios tested
      (1:3, 1:1 and 3:1), was supra-additive against electroconvulsions. The remaining
      combinations evaluated, i.e., LCZ with PB or VPA at fixed ratios of 1:3 and 3:1,
      as well as all fixed-ratio combinations between LCZ and PHT, were additive in the
      MES test in mice. Pharmacokinetic characterization revealed that LCZ
      significantly increased both free plasma and brain concentrations of CBZ and PHT,
      but was without effect on PB. Moreover, a bi-directional pharmacokinetic
      interaction between LCZ and VPA was observed in that while LCZ increased free
      plasma, but not total brain VPA concentrations, VPA increased the total brain,
      but not free plasma LCZ concentrations. Adverse-effect testing revealed that for
      all antiepileptic drug combinations neither motor performance nor long-term
      memory was altered. Of the drug combinations investigated, only that of LCZ and
      PB at the fixed ratio of 1:1 was not associated with any pharmacokinetic
      interactions, and thus it may be concluded that the supra-additive (synergistic)
      isobolographic interaction was pharmacodynamic in nature. Furthermore, the fact
      that LCZ and PB have similar mechanisms of action would suggest that drugs with
      similar mechanisms of action may provide rational polytherapy regimens.

PMID- 16604343
TI  - High-throughput bioanalysis with simultaneous acquisition of metabolic route data
      using ultra performance liquid chromatography coupled with time-of-flight mass
      spectrometry.
AB  - The capability of ultra performance liquid chromatography coupled with time-of
      flight mass spectrometry (UPLC/TOFMS) in the high-throughput quantitative
      analysis of a drug candidate in plasma has been investigated. Data obtained were
      compared with results from conventional analysis by high-performance liquid
      chromatography with tandem mass spectrometric detection on a triple quadrupole
      instrument (HPLC/MS/MS). The accuracies and precisions of the two approaches were
      comparable. The UPLC/TOFMS system displayed excellent robustness over the course
      of 276 injections of protein-precipitated plasma samples. With the
      instrumentation used, the limits of detection and quantification were
      approximately five-fold higher with UPLC/TOFMS than for HPLC/MS/MS. Nevertheless,
      the UPLC/TOFMS system proved adequate to quantify plasma concentrations of a drug
      molecule administered orally to rats at a pharmacologically relevant dose of 4
      mg/kg. As well as providing quantitative data on the test compound, it was also
      possible to extract data for eight different metabolites, including several
      isomeric species (three +O and three +2O) from the UPLC/TOFMS data sets, using an
      analytical method with a 2.5-minute run time. Selectivity for the test compound
      and its metabolites was derived from the accurate mass capabilities of the TOF
      instrument, and no MS method development was required.

PMID- 16604344
TI  - Medicine-related problems resulting in emergency department visits.
AB  - OBJECTIVE: Our aim was to estimate the prevalence of medicine-related problems,
      understood as negative clinical outcomes, that result in hospital emergency
      department (ED) visits and to establish relationships among risk factors and the
      appearance of pharmacotherapy negative outcomes. METHODS: Methods A stratified
      two-stage probabilistic sampling approach was used which consisted of stratified
      random sampling of patients visiting the ED followed up by interviews. A
      systematic appraisal tool was used to identify pharmacotherapy negative outcomes
      within the framework of the information gathered. Bivariate and multivariate
      analyses were carried out. Cost per process was estimated. RESULTS: The
      prevalence of pharmacotherapy negative outcomes producing ED visits was 33.17%
      (95%CI: 31.09-35.25). These negative outcomes could be divided into three
      categories: ineffectiveness (19.76%; 95%CI: 17.92-21.60), necessity/use (10.52%;
      95%CI: 9.48-11.56), and lack of safety (2.89%). About 73% (95%IC: 70.03-76.23) of
      the negative outcomes were considered to be preventable. Average cost per
      negative outcome was 329.5 euros (95%CI: 185.4-473.5). Factors associated with
      the appearance of negative outcomes were age, number of medicines taken, and the
      combined effect of both of these factors. Compared with those participants
      younger than 18 years, patients between 45 and 64 years of age presented an odds
      ratio (OR) of 2.52 (95%CI: 1.1-5.78), while those older than 65 years had an OR
      of 3.63 (95%CI: 1.27-10.35). Compared with people not using medicine(s), patients
      using one to two different medicines presented with an OR = 19.91 (95%CI: 8.28
      47.87), and those using more than three medicines had an OR = 22.71 (95%CI: 3.05
      69.26). Finally, compared with patients younger than 18 years and not using
      medicines, patients aged 45-64 years taking three or more different medicines
      presented with an OR = 64.07, while those older than 65 years taking three or
      more medicines presented with an OR = 31.50. CONCLUSION: The prevalence of
      negative clinical outcomes was 33%, of which more than 73% of these were
      preventable. Factors associated with their appearance were age, number of
      medicines, and their combined effect.

PMID- 16604345
TI  - Lymphatic mapping to tailor selective lymphadenectomy in cN0 tongue carcinoma:
      beyond the sentinel node concept.
AB  - PURPOSE: Cervical lymph node status is the most important pathological
      determinant of prognosis and decision making in head and neck squamous cell
      carcinoma (SCC). The aim of this study was to demonstrate that lymphoscintigraphy
      (LS) can supply a complete map of the lymphatic drainage before surgery, allowing
      planning of the type of intervention and serving to guide lymphadenectomy.
      METHODS: The study population comprised 14 patients with T2-4 SCCs of the tongue
      and clinically negative lymph nodes in the neck (cN0) who were scheduled to
      undergo tumour resection and selective level I-IV neck dissection extended to
      level V. LS was performed in all patients following the injection of (99m)Tc
      colloidal sulphide in three aliquots around the primary lesion. Dynamic, static
      and tomographic images of the head and neck were acquired. The operative
      specimens were subjected to lymphoscintigraphic evaluation. Preoperative and
      postoperative imaging results were compared with the pathological findings. All
      nodes were examined using haematoxylin-eosin staining. RESULTS: Preoperative LS
      was successful in all patients. Preferential pathways of lymphatic drainage were
      identified: level II of the neck was the most common lymphatic drainage pattern,
      followed by levels IV and III. Contralateral drainage occurred in 11 patients and
      in two of them metastatic nodes were found on the contralateral side. Metastases
      were observed only in radioactive lymph nodes. CONCLUSION: LS is able to supply a
      complete map of the lymphatic drainage before surgery, making it possible to
      tailor selective neck dissection to each individual patient based on the results
      of preoperative mapping, thereby sparing healthy lymphatic tissue and reducing
      surgery-related morbidity.

PMID- 16604346
TI  - Differentiation of tumour and inflammation: characterisation of [methyl
      3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human
      tumour and inflammatory cells.
AB  - PURPOSE: Previous studies suggest that radiolabelled amino acids could be
      superior to FDG in differentiating tumour and inflammation. Therefore the aim of
      this study was to investigate the uptake of FET and MET in human tumour and
      inflammatory cells and to investigate their uptake kinetics. METHODS: For uptake
      studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic
      studies were performed at variable concentrations of FET and MET. Competitive
      inhibition studies were done with BCH, MeAIB and L: -serine. RESULTS: All
      inflammatory cells incorporated more MET than the tumour cells. The uptake of
      FET, in contrast, was significantly lower in all inflammatory cells than in the
      tumour cells. In tumour cells the uptake of MET was about five times the uptake
      of FET. The competitive inhibitors reduced uptake of both tracers to 20-40% in
      tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET
      and FET transport was saturable in all cells except macrophages and followed a
      Michaelis-Menten kinetic. Highest capacity (V (max)) and affinity (K (m)) for the
      uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake
      were highest in the DHL-4 cells. CONCLUSION: In contrast to MET, FET accumulated
      to a significantly greater extent in tumour cells than in inflammatory cells. The
      marked differences between tumour and inflammatory cells concerning FET and MET
      uptake suggest that FET and MET are substrates of different subtypes of the L
      system.

PMID- 16604347
TI  - Raynaud's syndrome: comparison of late and early onset forms using hand perfusion
      scintigraphy.
AB  - Primary Raynaud's disease is generally a disease of younger females; however,
      there are cases where symptoms present over the age of 40. These cases are
      described as late onset. In our current prospective study we compared the
      characteristics of early and late onset types of primary Raynaud's in 127
      patients. In addition to the collection of medical records, we performed
      capillary-microscopy and hand perfusion scintigraphy using Tc-99 m DTPA to
      evaluate the microcirculation of each patient's fingers. Regarding the spectrum
      of the capillary-microscopic findings, we did not find any significant difference
      between the early and late onset forms. However, in hand perfusion examinations
      done using Tc-99 m DTPA, we measured a significantly lower finger/palm ratio
      (FPR) in the early onset group of patients. We also observed a correlation
      between the duration of the disease and the FPR, as well as between the age and
      FPR. Longer disease duration resulted in a significantly lower FPR. On the basis
      of our results, we believe that late onset Raynaud's should be treated as a
      separate entity. Due to its different characteristics found on examination and
      follow-up of our patients, functional hand perfusion examination should be
      recommended independently of the age-related characteristics of the disease.

PMID- 16604348
TI  - The effect of beta-bungarotoxin, or geniculate ganglion lesion on taste bud
      development in the chick embryo.
AB  - Chick taste bud (gemmal) primordia normally appear on embryonic day (E) 16 and
      incipient immature, spherical-shaped buds at E17. In ovo injection of beta
      bungarotoxin at E12 resulted in a complete absence of taste buds in lower beak
      and palatal epithelium at developmental ages E17 and E21. However, putative
      gemmal primordia (solitary clear cells; small, cell groupings) remained, lying
      adjacent to salivary gland duct openings as seen in normal chick gemmal
      development. Oral epithelium was immunonegative to neural cell adhesion molecule
      (NCAM) suggesting gemmal primordia are nerve-independent. Some NCAM
      immunoreactivity was evident in autonomic ganglion-like cells and nerve fibers in
      connective tissue. After unilateral geniculate ganglion/otocyst excision on E2.5,
      at developmental ages E18 and posthatching day 1, approximately 12% of surviving
      ipsilateral geniculate ganglion cells sustained approximately 54% of the
      unoperated gemmal counts. After E18, proportional stages of differentiation in
      surviving developing buds probably reflect their degree of innervation, as well
      as rate of differentiation. Irrespective of the degree of geniculate ganglion
      damage, the proportion of surviving buds can be sustained at the same
      differentiated bud stage as on the unoperated side, or may differentiate to a
      later bud stage, consistent with the thesis that bud maturation, maintenance, and
      survival are nerve-dependent.

PMID- 16604349
TI  - The regeneration capacity of the flatworm Macrostomum lignano--on repeated
      regeneration, rejuvenation, and the minimal size needed for regeneration.
AB  - The lion's share of studies on regeneration in Plathelminthes (flatworms) has
      been so far carried out on a derived taxon of rhabditophorans, the freshwater
      planarians (Tricladida), and has shown this group's outstanding regeneration
      capabilities in detail. Sharing a likely totipotent stem cell system, many other
      flatworm taxa are capable of regeneration as well. In this paper, we present the
      regeneration capacity of Macrostomum lignano, a representative of the
      Macrostomorpha, the basal-most taxon of rhabditophoran flatworms and one of the
      most basal extant bilaterian protostomes. Amputated or incised transversally,
      obliquely, and longitudinally at various cutting levels, M. lignano is able to
      regenerate the anterior-most body part (the rostrum) and any part posterior of
      the pharynx, but cannot regenerate a head. Repeated regeneration was observed for
      29 successive amputations over a period of almost 12 months. Besides adults, also
      first-day hatchlings and older juveniles were shown to regenerate after
      transversal cutting. The minimum number of cells required for regeneration in
      adults (with a total of 25,000 cells) is 4,000, including 160 neoblasts. In
      hatchlings only 1,500 cells, including 50 neoblasts, are needed for regeneration.
      The life span of untreated M. lignano was determined to be about 10 months.

PMID- 16604350
TI  - Genome scans and gene expression microarrays converge to identify gene regulatory
      loci relevant in schizophrenia.
AB  - Multiple linkage regions have been reported in schizophrenia, and some appear to
      harbor susceptibility genes that are differentially expressed in postmortem brain
      tissue derived from unrelated individuals. We combined traditional genome-wide
      linkage analysis in a multiplex family with lymphocytic genome-wide expression
      analysis. A genome scan suggested linkage to a chromosome 4q marker (D4S1530, LOD
      2.17, theta = 0) using a dominant model. Haplotype analysis using flanking
      microsatellite markers delineated a 14 Mb region that cosegregated with all those
      affected. Subsequent genome-wide scan with SNP genotypes supported the evidence
      of linkage to 4q33-35.1 (LOD = 2.39) using a dominant model. Genome-wide
      microarray analysis of five affected and five unaffected family members
      identified two differentially expressed genes within the haplotype AGA and GALNT7
      (aspartylglucosaminidase and UDP-N-acetyl-alpha-D-galactosamine: polypeptide N
      acetylgalactosaminyltransferase 7) with nominal significance; however, these
      genes did not remain significant following analysis of covariance. We carried out
      genome-wide linkage analyses between the quantitative expression phenotype and
      genetic markers. AGA expression levels showed suggestive linkage to multiple
      markers in the haplotype (maximum LOD = 2.37) but to no other genomic region.
      GALNT7 expression levels showed linkage to regulatory loci at 4q28.1 (maximum LOD
      = 3.15) and in the haplotype region at 4q33-35.1 (maximum LOD = 2.37). ADH1B
      (alcohol dehydrogenase IB) was linked to loci at 4q21-q23 (maximum LOD = 3.08)
      and haplotype region at 4q33-35.1 (maximum LOD = 2.27). Seven differentially
      expressed genes were validated with RT-PCR. Three genes in the 4q33-35.1
      haplotype region were also differentially expressed in schizophrenia in
      postmortem dorsolateral prefrontal cortex: AGA, HMGB2, and SCRG1. These results
      indicate that combining differential gene expression with linkage analysis may
      help in identifying candidate genes and potential regulatory sites. Moreover,
      they also replicate recent findings of complex trans- and cis- regulation of
      genes.

PMID- 16604352
TI  - Unmet needs of cancer survivors: supportive care's new challenge.

PMID- 16604353
TI  - Dorsal root ganglionectomy for pseudotumor of the L3 dorsal root ganglion: a rare
      case and a rare treatment.
AB  - Dorsal root ganglia are oval enlargements on the dorsal nerve roots and contain
      the cell bodies of sensory neurons. Asymmetry of dorsal root ganglia may occur
      naturally, yet natural occurrence of gigantic dorsal root ganglion (DRG) is rare.
      The patient was 61-year-old woman who presented with atypical symptoms like
      neuropathic pain and urinary distention. Neuroimaging has shown left L3-4 far
      lateral disc herniation and a gigantic L3 DRG. At surgery, the dural sheath of
      the ganglion had to be opened and a firm, yellow-colored abnormal tissue was
      exposed. The abnormal tissue considered to be a tumor of neural origin was gross
      totally excised and the patient's symptoms ceased immediately after surgery.
      Histopathological examination of the specimen revealed nothing more than normal
      DRG morphology. At 4 months postoperatively, the patient is well with mild L3
      hyperesthesia and hyperalgesia. Dural sheath opening in neurosurgery is not a
      routine practice. The sheath may need to be opened when surgeon suspects of a
      tumor, a free disc fragment and any inflammation within the ganglion. Operative
      morphology of a severely edematous but non-tumoral (pseudotumor) ganglion has not
      previously been documented.

PMID- 16604351
TI  - Cancer chemotherapy-induced diarrhoea and constipation: mechanisms of damage and
      prevention strategies.
AB  - BACKGROUND: Diarrhoea and constipation are common toxicities of chemotherapy, and
      both are poorly understood. They are manifestations of alimentary mucositis, a
      condition which affects the entire gastrointestinal tract. DISCUSSION: The
      absolute percentage of patients that have diarrhoea or constipation as a result
      of their treatment has yet to be fully defined, although general estimates place
      10% of patients with advanced cancer as being afflicted. Although there has been
      some major progress in recent years with understanding the mechanisms of oral and
      small intestinal mucositis, diarrhoea and constipation have received very little
      attention. Although diarrhoea is a well-recognised side-effect of both
      chemotherapy and radiotherapy, very little research has been conducted on the
      mechanisms behind diarrhoea or its treatment. Much of the information in the
      published literature is based on clinical observations with very little basic
      science existing. Constipation is not as well recognised and very little is known
      about its mechanisms. OBJECTIVES: This review will examine in detail the
      potentially complex pathogenesis of post-chemotherapy diarrhoea in both animal
      models and the clinical setting. Furthermore, it will explore what is known about
      chemotherapy-induced constipation. It will then outline an evidence-based pathway
      for the investigation and treatment of post-chemotherapy diarrhoea and
      constipation.

PMID- 16604355
TI  - Anterior retropharyngeal fixation C1-2 for stabilization of atlantoaxial
      instabilities: study of feasibility, technical description and preliminary
      results.
AB  - Posterior transarticular screw fixation C1-2 with the Magerl technique is a
      challenging procedure for stabilization of atlantoaxial instabilities. Although
      its high primary stability favoured it to sublaminar wire-based techniques, the
      close merging of the vertebral artery (VA) and its violation during screw passage
      inside the axis emphasizes its potential risk. Also, posterior approach to the
      upper cervical spine produces extensive, as well as traumatic soft-tissue
      stripping. In comparison, anterior transarticular screw fixation C1-2 is an
      atraumatic technique, but has been neglected in the literature, even though
      promising results are published and lectured to date. In 2004, anterior screw
      fixation C1-2 was introduced in our department for the treatment of atlantoaxial
      instabilities. As it showed convincing results, its general anatomic feasibility
      was worked up. The distance between mid-sagittal line of C2 and medial border of
      the VA groove resembles the most important anatomic landmark in anterior
      transarticular screw fixation C1-2. Therefore, CT based measurements on 42
      healthy specimens without pathology of the cervical spine were performed. Our
      data are compiled in an extended collection of anatomic landmarks relevant for
      anterior transarticular screw fixation C1-2. Based on anatomic findings, the
      technique and its feasibility in daily clinical work is depicted and discussed on
      our preliminary results in seven patients.

PMID- 16604354
TI  - Electrical stimulation therapies for spinal fusions: current concepts.
AB  - Electrical stimulation therapies have been used for more than 30 years to enhance
      spinal fusions. Although their positive effects on spinal fusions have been
      widely reported, the mechanisms of action of the technologies were only recently
      identified. Three types of technologies are available clinically: direct current,
      capacitive coupling, and inductive coupling. The latter is the basis of pulsed
      electromagnetic fields and combined magnetic fields. This review summarizes the
      current concepts on the mechanisms of action, animal and clinical studies, and
      cost justification for the use of electrical stimulation for spinal fusions.
      Scientific studies support the validity of electrical stimulation treatments. The
      mechanisms of action of each of the three electrical stimulation therapies are
      different. New data demonstrates that the upregulation of several growth factors
      may be responsible for the clinical success seen with the use of such
      technologies.

PMID- 16604356
TI  - Catalysis of regioselective reduction of NAD+ by ruthenium(II) arene complexes
      under biologically relevant conditions.
AB  - Ruthenium(II) arene anticancer complexes [(eta6-arene)Ru(en)Cl]PF6 (arene is
      hexamethylbenzene, p-cymene, indan; en is ethylenediamine) can catalyse
      regioselective reduction of NAD+ by formate in water to form 1,4-NADH, at pD 7.2,
      37 degrees C, and in the presence of air. The catalytic activity is markedly
      dependent on the arene, with the hexamethylbenzene (hmb) complex showing the
      highest activity. For [(eta 6-hmb)Ru(en)Cl]PF6, the rate of reaction is
      independent of NAD+ concentration and shows saturation kinetics with respect to
      formate concentration. A Km value of 58 mM and a turnover frequency at saturation
      of 1.46 h(-1) were observed. Removal of chloride and performing the reaction
      under argon led to higher reaction rates. Lung cancer cells (A549) were found to
      be remarkably tolerant to formate even at millimolar concentrations. The
      possibility of using ruthenium arene complexes coadministered with formate as
      catalytic drugs is discussed.

PMID- 16604357
TI  - DNA microarray analysis of anaerobic Methanosarcina barkeri reveals responses to
      heat shock and air exposure.
AB  - Methanosarcina barkeri is a methanogenic archaeon that can digest cellulose and
      other polysaccharides to produce methane. It can only grow under strictly anoxic
      conditions, but which can survive air exposure. To obtain further knowledge of
      cellular changes occurring in M. barkeri in response to air exposure and other
      environmental stresses, we constructed the first oligonucleotide microarray for
      M. barkeri and used it to investigate the global transcriptomic responses of M.
      barkeri to air exposure and heat shock at 45 degrees C for 1 h. The results
      showed that various house-keeping genes, such as genes involved in DNA
      replication recombination and repair, energy production and conversion, and
      protein turnover were regulated by environmental stimuli. In response to air
      exposure, up-regulation of a large number of transposase encoding genes was
      observed. However, no differential expression of genes encoding superoxide
      dismutase, catalase, nonspecific peroxidases or thioredoxin reductase was
      observed in response to air exposure, implying that no significant level of
      reactive oxygen species has been formed under air exposure. In response to heat
      shock, both Hsp70 (DnaK-DnaJ-GrpE chaperone system) the Hsp60 (GroEL) systems
      were up-regulated, suggesting that they may play an important role in protein
      biogenesis in M. barkeri during heat stress.

PMID- 16604358
TI  - Interferon-gamma potentiates endoplasmic reticulum stress-induced death by
      reducing pancreatic beta cell defence mechanisms.
AB  - AIMS/HYPOTHESIS: A tight control of endoplasmic reticulum homeostasis is crucial
      for beta cell function and survival. We recently described that IL-1beta plus IFN
      gamma deplete endoplasmic reticulum Ca2+ stores in beta cells, leading to
      endoplasmic reticulum stress and apoptosis. IL-1beta alone induced endoplasmic
      reticulum stress but failed to induce beta cell death, while IFN-gamma alone
      neither caused endoplasmic reticulum stress nor induced beta cell death. This
      suggests that IFN-gamma aggravates endoplasmic reticulum stress induced by IL
      1beta, eventually triggering apoptosis. Here we tested this hypothesis and the
      mechanisms involved, by investigating the effects of IFN-gamma on endoplasmic
      reticulum-stress-induced beta cell apoptosis caused by a specific blocker of the
      sarcoendoplasmic-reticulum pump Ca2+-ATPase (SERCA). MATERIALS AND METHODS: INS
      1E cells or beta cells were pretreated with IFN-gamma and then exposed to the
      SERCA blocker cyclopiazonic acid (CPA) for induction of endoplasmic reticulum
      stress. Cell death was evaluated by Hoechst 342 and propidium iodide staining.
      Expression of genes related to endoplasmic reticulum stress was determined by
      real-time RT-PCR, while activation of the endoplasmic reticulum stress response
      was determined by analysing X-box binding protein-1 (Xbp1) splicing and using a
      reporter construct containing five copies of the unfolded protein response
      element (UPRE). RESULTS: CPA induces endoplasmic reticulum stress and apoptosis
      in insulin-producing cells. Pretreatment with IFN-gamma decreased the basal level
      of spliced Xbp1 mRNA, the basal and CPA-induced activity of the UPRE reporter,
      and the mRNA expression of several endoplasmic reticulum chaperones (Bip, Grp94
      and Orp 150) and Sec61a. Furthermore, CPA-induced Chop mRNA expression and beta
      cell apoptosis were potentiated in cells that had been pretreated with IFN-gamma.
      CONCLUSIONS/INTERPRETATION: CPA-induced endoplasmic reticulum stress and
      apoptosis is enhanced in IFN-gamma-treated beta cells. These effects are mediated
      via downregulation of the expression of genes involved in beta cell defence
      against endoplasmic reticulum stress.

PMID- 16604359
TI  - Mid-term results of arthroscopic reconstruction in chronic posterior cruciate
      ligament instability.
AB  - The purpose of this study was to evaluate the clinical results of arthroscopic
      single bundle posterior cruciate ligament (PCL) reconstruction in patients with
      chronic PCL instability not responding to conservative treatment. 18 patients
      were available for follow-up with an average elapsed time of 3 years between
      onset of injury and surgery and an average duration of 3.3 years between
      reconstruction and evaluation. The clinical results were investigated using the
      IKDC form, the Tegner rating system, a subjective evaluation, and the VAS for
      pain rating. The presence of femoral degenerative changes correlated strongly to
      the elapsed time between injury and operation (P<0.05). Before surgery all
      patients were graded D (severely abnormal) using the IKDC evaluation form. The
      final IKDC score at follow-up resulted in grade A (normal) in five patients
      (28%), grade B (nearly normal) in eight patients (44%), grade C (abnormal) in
      four patients (22%) and grade D (severely abnormal) in one patient (6%). The VAS
      score for pain rating revealed very few complaints of pain and it demonstrated a
      strong correlation between the subjective evaluation and the Tegner rating score
      (P<0.01). Evaluation of the Tegner score resulted in a significant improvement
      after surgery when compared to the situation prior to operation (P<0.01).
      Although there still is some controversy on the indication for treatment of PCL
      injury, we conclude on the basis of our findings that arthroscopic reconstruction
      of symptomatic chronic PCL instability, not responding to conservative therapy,
      can be greatly beneficial.

PMID- 16604360
TI  - Lipids as renewable resources: current state of chemical and biotechnological
      conversion and diversification.
AB  - Oils and fats are the most important renewable raw materials of the chemical
      industry. They make available fatty acids in such purity that they may be used
      for chemical conversions and for the synthesis of chemically pure compounds.
      Oleic acid (1) from "new sunflower," linoleic acid (2) from soybean, linolenic
      acid (3) from linseed, erucic acid (4) from rape seed, and ricinoleic acid (5)
      from castor oil are most important for chemical transformations offering in
      addition to the carboxy group one or more C-C-double bonds. New plant oils
      containing fatty acids with new and interesting functionalities such as
      petroselinic acid (6) from Coriandrum sativum, calendic acid (7) from Calendula
      officinalis, alpha-eleostearic acid (8) from tung oil, santalbic acid (9) from
      Santalum album (Linn.), and vernolic acid (10) from Vernonia galamensis are
      becoming industrially available. The basic oleochemicals are free fatty acids,
      methyl esters, fatty alcohols, and fatty amines as well as glycerol as a by
      product. Their interesting new industrial applications are the usage as
      environmentally friendly industrial fluids and lubricants, insulating fluid for
      electric utilities such as transformers and additive to asphalt. Modern methods
      of synthetic organic chemistry including enzymatic and microbial transformations
      were applied extensively to fatty compounds for the selective functionalization
      of the alkyl chain. Syntheses of long-chain diacids, omega-hydroxy fatty acids,
      and omega-unsaturated fatty acids as base chemicals derived from vegetable oils
      were developed. Interesting applications were opened by the epoxidation of C-C
      double bonds giving the possibility of photochemically initiated cationic curing
      and access to polyetherpolyols. Enantiomerically pure fatty acids as part of the
      chiral pool of nature can be used for the synthesis of nonracemic building
      blocks.

PMID- 16604361
TI  - Video-endoscopy and digital image analysis of the nasal valve area.
AB  - The aim of this study was to evaluate the benefit of digital image analysis of
      video-endoscopic images of the valve area to study changes in cross-sections of
      the nasal valve area before and after nasal surgery. Fifty patients scheduled for
      septoplasty or septorhinoplasty were included. Successful recordings of the valve
      area and digitally calculated cross-sections of the nasal valve area served as
      main outcome measures. First, various endoscopes (rigid 0 degrees - and 25
      degrees -endoscopes and fibreoptic 0 degrees -endoscope) were tested and video
      endoscopy was standardised in 39 patients. Second, preoperative and postoperative
      images of the nasal valve area in 11 patients with obstruction of the nasal valve
      area were digitally analysed and compared. In these patients, a significant
      widening of the valve area could be shown postoperatively. We conclude that
      digital image analysis of the nasal valve area can be helpful in the measurement
      of cross-sections of the nasal valve area before and after nasal surgical
      procedures in selected patients.

PMID- 16604362
TI  - Perforation of the pulmonary artery by a bronchial wall stent.
AB  - Implantation of stents into the bronchial walls is a newly developed method to
      treat lung emphysema, which is now being tested clinically. During this
      procedure, a bronchoscope carrying a Doppler ultrasonography head is placed into
      a segmental bronchus and the blood vessels running in parallel to the bronchus
      are localized. Once a safe location without blood vessels is found, the bronchial
      wall is perforated and a stent is placed within the wall to improve the
      expiratory volume of these "bypasses" to the adjacent lung parenchyma. We
      observed a fatal complication with this method in a 60-year-old man. The
      bronchial wall and the pulmonary artery were perforated by one of the stents
      inducing massive bleeding, which could not be stopped. The patient died due to
      aspiration of blood in combination with massive loss of blood. The general risk
      to perforate the pulmonary artery during this procedure cannot be estimated from
      this single observation but should be considered regarding the legal and clinical
      aspects.

PMID- 16604363
TI  - Mother-child exclusion due to paternal uniparental disomy 6.
AB  - In a mother-child pair, false exclusions in markers on chromosome 6 have been
      observed. The genetic incompatibilities have been caused by paternal uniparental
      disomy. The consequences of such cases for investigations of parentage are
      discussed.

PMID- 16604364
TI  - Gunshot-related transport of micro-organisms from the skin of the entrance region
      into the bullet path.
AB  - The skin defect of a gunshot entrance wound is caused by the retrograde and
      anterograde displacement of skin particles. In the present study, we investigated
      whether gunshots to bacterially contaminated skin are associated with the
      transport of micro-organisms into the bullet path. The shots were fired into
      composite models of pig skin and gelatin blocks. The outer surface of the skin
      was covered with a thin layer of a defined bacterial suspension [green
      fluorescent protein-labelled Escherichia coli in the preliminary test and
      Staphylococcus epidermidis, DSM 1798, in the main test series]. After the
      bacterially contaminated fluid had dried, test shots were fired from a distance
      of 5 and 10 m using calibre .38 Special cartridges with different bullet types
      (round nose, truncated cone, hollow point and flat nose). Subsequent
      bacteriological analyses showed that all the bullet tracks in the gelatin serving
      as tissue simulant contained displaced micro-organisms from the skin surface. The
      results are presented and discussed with reference to the transport of skin
      particles into the depth of the wound track.

PMID- 16604365
TI  - Employment and disability for work in patients with COPD: a cross-sectional study
      among Dutch patients.
AB  - OBJECTIVES: The aim was to gain insight into work experiences and problems of
      subjects with chronic obstructive pulmonary disease (COPD) to develop more
      effective guidelines for preventing work disability and work loss. METHODS: A
      total of 617 patients aged 45-60, recruited from pulmonary outpatient clinics and
      general practices, completed a questionnaire on (respiratory) health and work
      history. RESULTS: Of the patients 43% were female, 52% were employed and more
      than half were less educated. Comorbidity was present in 52% of the study group.
      Of those who stopped working (N=260), 36% stopped before the onset of COPD, 39%
      stopped because of COPD and 25%, although having COPD, had other reasons to stop.
      Of the patients with a work history 39% had an invalidity benefit: 21% of the
      working and 60% of the non-working patients. For one-third of these patients COPD
      was not the reason for having an invalidity benefit. For 56% of those who had a
      benefit because of COPD, comorbidity contributed to work disability. No
      difference in current smoking habit was seen between working patients and non
      working patients. Yet, non-working patients were more often smokers at the moment
      they stopped working. Furthermore, former smokers who still worked stopped
      smoking at a younger age than former smokers who stopped working. Compared with
      workers and independent of smoking habit, former workers were more exposed to
      dust/irritants, had their work(place) less frequently modified and had more
      unfavourable (social) work experiences. CONCLUSION: For employees with COPD, work
      loss is often multi-factorial. Comorbidity is often present and an important
      cause for work loss. Therefore occupational health guidance has to take other
      interfering (health) factors than COPD into consideration as well. In preventing
      work disability, work(place) adjustment merits more attention.

PMID- 16604367
TI  - Purinergic modulation of synaptic signalling at the neuromuscular junction.
AB  - Purines have physiologically important functions throughout the nervous system.
      In both the central (CNS) and peripheral nervous systems (PNS), purines in the
      form of adenosine triphosphate and adenosine can play a number of roles in
      neuronal activation and inhibition. In addition, purines are known to be
      important for glial cell signaling in both the CNS and PNS. In the PNS, the
      neuromuscular junction (NMJ) is an excellent model for studying simple synaptic
      interactions. It is well suited to investigations of neuron-glia interactions
      because synaptic properties are well defined and perisynaptic Schwann cells
      (PSCs), glial cells at the NMJ, dynamically interact with the pre- and
      postsynaptic elements. At the NMJ, purines are critical for presynaptic
      modulation but also for neuron-glia interactions. Purines signal to PSCs through
      metabotropic and ionotropic receptors and activation of these receptors can have
      both modulatory and activating functions. This review will discuss recent
      developments in our understanding of purinergic modulation of the NMJ with an
      emphasis on the involvement of purines in neuron-glia interactions at this
      synapse.

PMID- 16604366
TI  - Recording, analysis, and function of dendritic voltage-gated channels.
AB  - Ever since the publication of the Hamill et al. [Hamill et al., Pflugers Arch,
      391:85-100, 1981] paper and the following increase in popularity of acute brain
      slice preparations, there has been a large increase in the volume of publications
      investigating voltage-gated channels in the central nervous system using the
      patch-clamp technique. In the preceding decade, investigations of voltage-gated
      channels have moved out of the somatic region into dendrites providing much
      needed information about dendritic voltage-gated channels. In this study, we
      review some aspects related to the investigation of voltage-gated ion channels in
      dendrites: recording, analysis, and function.

PMID- 16604368
TI  - Pitfalls when examining gap junction hemichannels: interference from volume
      regulated anion channels.
AB  - Human HeLa cells transfected with mouse connexin45 were used to explore the
      experimental conditions suitable to measure currents carried by gap junction
      hemichannels. Experiments were performed with a voltage-clamp technique and whole
      cell recording. Lowering [Ca(2+)](o) from 2 mM to 20 nM evoked an extra current,
      I (m), putatively carried by Cx45 hemichannels. However, the variability of I (m)
      (size, voltage sensitivity, kinetics) suggested the involvement of other
      channels. The finding that growth medium in the incubator increased the
      osmolarity with time implied that volume-regulated anion channels (VRAC) may
      participate. This assumption was reinforced by the following observations. On the
      one hand, keeping [Ca(2+)](o) normal while the osmolarity of the extracellular
      solution was reduced from 310 to 290 mOsm yielded a current characteristic of
      VRAC; I (VRAC) activated/deactivated at negative/positive voltage, giving rise to
      the conductance functions g (VRAC,inst)=f(V (m)) (inst: instantaneous; V (m):
      membrane potential) and g (VRAC,ss)=f(V (m)) (ss: steady state). Moreover, it was
      reversibly inhibited by mibefradil, a Cl(-)channel blocker (binding constant K
      (d)=38 microM, Hill coefficient n=12), but not by the gap junction channel
      blocker 18alpha-glycyrrhetinic acid. On the other hand, minimizing the osmotic
      imbalance while [Ca(2+)](o) was reduced led to a current typical for Cx45
      hemichannels; I (hc) activated/deactivated at positive/negative voltage.
      Furthermore, it was reversibly inhibited by 18alpha-glycyrrhetinic acid or
      palmitoleic acid, but not by mibefradil. Computations based on g (VRAC,ss)=f(V
      (m)) and g (hc,ss)=f(V (m)) indicated that the concomitant operation of both
      currents results in a bell-shaped conductance-voltage relationship. The
      functional implications of the data presented are discussed. Conceivably, VRAC
      and hemichannels are involved in a common signaling pathway.

PMID- 16604370
TI  - Size correction: comparing morphological traits among populations and
      environments.
AB  - Morphological relationships change with overall body size and body size often
      varies among populations. Therefore, quantitative analyses of individual traits
      from organisms in different populations or environments (e.g., in studies of
      phenotypic plasticity) often adjust for differences in body size to isolate
      changes in allometry. Most studies of among population variation in morphology
      either (1) use analysis of covariance (ANCOVA) with a univariate measure of body
      size as the covariate, or (2) compare residuals from ordinary least squares
      regression of each trait against body size or the first principal component of
      the pooled data (shearing). However, both approaches are problematic. ANCOVA
      depends on assumptions (small variance in the covariate) that are frequently
      violated in this context. Residuals analysis assumes that scaling relationships
      within groups are equal, but this assumption is rarely tested. Furthermore,
      scaling relationships obtained from pooled data typically mischaracterize within
      group scaling relationships. We discuss potential biases imposed by the
      application of ANCOVA and residuals analysis for quantifying morphological
      differences, and elaborate and demonstrate a more effective alternative: common
      principal components analysis combined with Burnaby's back-projection method.

PMID- 16604369
TI  - ABCC6 and pseudoxanthoma elasticum.
AB  - ABCC6 belongs to the adenosine triphosphate-binding cassette (ABC) gene subfamily
      C. This protein family is involved in a large variety of physiological processes,
      such as signal transduction, protein secretion, drug and antibiotic resistance,
      and antigen presentation [Kool et al. (1999) 59:175-182; Borst and Elferink
      (2002) 71:537-592]. ABCC6 is primarily and highly expressed in the liver and
      kidney [Kool et al. (1999) 59:175-182; Bergen et al. (2000) 25:228-2231]. The
      precise physiological function and natural substrate(s) transported by ABCC6 are
      unknown, but the protein may be involved in active transport of intracellular
      compounds to the extracellular environment [Kool et al. (1999) 59:175-182]
      [Scheffer et al. (2002) 82:515-518]. Recently, it was shown that loss of function
      mutations in ABCC6 cause pseudoxanthoma elasticum (PXE) [Bergen et al. (2000)
      25:228-2231; Le Saux et al. (2000) 25:223-227]. PXE is an autosomal recessively
      inherited multi-organ disorder [Goodman et al. (1963) 42:297-334; Lebwohl et al.
      (1994) 30:103-107]. PXE is primarily associated with the accumulation of
      mineralized and fragmented elastic fibers of the connective tissue in the skin
      [Neldner (1988) 6:1-159], Bruch's membrane in the retina [Hu et al. (2003) 48:424
      438], and vessel walls [Kornet et al. (2004) 30:1041-1048]. PXE patients usually
      have skin lesions and breaks in Bruch's membrane of the retina (angioid streaks).
      Also, a variety of cardiovascular complications has been observed [Hu et al.
      (2003) 48:424-438]. Recently, a mouse model for PXE was created by targeted
      disruption of Abcc6 [Gorgels et al. (2005) 14:1763-1773; Klement et al. (2005)
      25:8299-8310], which may be useful to elucidate the precise function of Abcc6 and
      to develop experimental therapies.

PMID- 16604372
TI  - Pediatric C1q nephropathy and incidental proteinuria.

PMID- 16604373
TI  - Accumulation of poly(ADP-ribose) polymerase inhibitors in children with chronic
      renal failure.
AB  - Nicotinamide, N-methyl-2-pyridone-5-carboxamide (Met2PY) and N-methyl-4-pyridone
      3-carboxamide (Met4PY) are biological metabolites of the intracellular coenzyme
      nicotinamide adenine dinucleotide (NAD) that can potentially inhibit poly(ADP
      ribose) polymerase 1 (PARP-1; DNA repair enzyme). Our research was aimed at
      establishing whether chronic renal failure (CRF) in children leads to the
      elevation of plasma NAD metabolites sufficient to inhibit PARP-1 activity.
      Nicotinamide, Met2PY and Met4PY plasma and erythrocyte concentrations were
      measured in 25 children with CRF and in 19 healthy children. The effect of these
      NAD metabolites on PARP-1 activity was studied in vitro. We found that plasma
      concentration of all NAD metabolites (nicotinamide, Met2PY, Met4PY) in children
      with CRF could reach the concentration of 2, 30 and 10 microM as compared to 0.2,
      1 and 0.5 microM, respectively, in healthy children. The concentration of
      nicotinamide metabolites correlated positively with plasma creatinine
      concentration and negatively with creatinine clearance in children with CRF. We
      found that Met2PY, Met4PY and nicotinamide inhibited in vitro PARP-1 activity
      with IC50 values of 2.1, 0.18 and 0.12 mM, respectively. Our data indicate that
      NAD metabolites accumulate in plasma of children with CRF and their combined
      effect could lead to the inhibition of PARP-1 activity. NAD metabolites could be
      particularly harmful in children due to higher DNA turnover than in adults.

PMID- 16604374
TI  - Central neurocytoma: a novel appraisal of a polymorphic pathology. Our experience
      and a review of the literature.
AB  - Central neurocytoma should be considered in the differential diagnosis of
      intraventricular tumours. The records of 20 patients operated on between 1975 and
      2000 for central neurocytoma were retrospectively reviewed, and the histological
      gradings and clinical outcomes were compared. On the basis of our previous cases,
      in the latter five of this series, the following therapeutic protocol was
      adopted. In those cases in which total removal was achieved, no further treatment
      was given if the MIB-1 index was <4%; vice versa, if it was >4%, a course of
      conformational radiotherapy was delivered. In subtotally removed cases,
      radiosurgery with linac was also performed (median dose 20 Gy) as well as
      conformational radiotherapy whenever there was a recurrence of the lesion (median
      dose 45 Gy). In cases in which there was only partial cytoreduction,
      conformational radiotherapy was administered with the adjunct of polychemotherapy
      if the MIB-1 was >4%. Twenty patients were surgically treated: 11 men and nine
      women, with an average age of 26 years (range 17 years to 42 years).Total,
      subtotal and partial removals were achieved in, respectively, ten, three and
      seven cases. At average follow-up of 7 years, 16 patients had been cured, had
      significantly improved or were at least stable [Karnofsky performance status
      score (KPS)] >70 or more)]. On the other hand, four patients had worsened; of
      these, two had died and two had a KPS=50 and an unfavourable prognosis. The
      presence of histological atypia has proved to be a significantly negative risk
      factor for survival (P=0.02) while an MIB score >4% was significantly correlated
      with an unfavourable outcome (death or worsening of neurological status). The
      "atypical" neurocytoma seems to be a distinct entity, with a less favourable
      prognosis and a higher tendency to recur.

PMID- 16604375
TI  - Production of marker-free transgenic Nierembergia caerulea using MAT vector
      system.
AB  - Agrobacterium tumefaciens strain EHA105 harboring an ipt-type MAT vector,
      pNPI132, was used to produce morphologically normal transgenic Nierembergia
      caerulea cv. Mont Blanc employing ipt gene as the selectable marker gene. beta
      glucuronidase (GUS) gene was used as model gene of interest. The MAT vector
      system is a positive selection system that gives the advantage of regeneration to
      the transgenic cells without killing the non-transgenic cells. Infected explants
      were cultured on hormone- and antibiotic-free MS medium, and 65% of the
      regenerated shoots developed ipt shooty phenotype-morphologically abnormal
      shoots, within approximately 3 months after co-cultivation. Twenty
      morphologically normal shoots were produced from 12 transgenic ipt shoots 7
      months after co-cultivation. The normal shoots rooted well on hormone-free MS
      medium. Ninety percent of the normal shoots were ipt (-), GUS(+) and excision(+)
      as determined by PCR and Southern blot analyses. These results indicate that ipt
      type MAT vector system can be used successfully in Nierembergia to produce marker
      free transgenic plants without using phytohormones and selective chemical agents.

PMID- 16604376
TI  - Radiofrequency-ablation of unresectable primary and secondary liver tumors:
      results in 88 patients.
AB  - BACKGROUND AND AIMS: Radiofrequency-ablation (RFA) is increasingly used for
      destruction of unresectable primary and secondary liver tumors. We report our
      experience in the use of RFA for the management of unresectable hepatic
      malignancies. PATIENTS AND METHODS: Between February 2000 and December 2004 we
      have undertaken 120 RFA procedures to ablate 426 unresectable primary or
      metastatic liver tumors in 88 patients. RFA was performed via laparotomy (n=68),
      laparoscopy (n=9) or a percutaneous approach (n=43). Primary liver cancer was
      treated in seven patients (8%) and metastatic liver tumors were treated in 81
      patients (92%). All patients were followed to assess complications, treatment
      response and recurrence of malignant disease. RESULTS: Procedure-related
      complication rate was low (3.4%). During a mean follow-up of 21.2 months, 15
      patients had local tumor progression (17%), 21 patients (23.9%) had new malignant
      disease and 27 patients (30.7%) died from intervention-unrelated complications of
      their malignant disease. Additional liver lesions were identified in 27 (35%) of
      77 cases by intraoperative ultrasound. Thirty-six patients received simultaneous
      resection and RFA. CONCLUSION: RFA is a safe, well-tolerated and effective
      treatment for patients with unresectable primary and secondary liver
      malignancies.

PMID- 16604378
TI  - Depression, suicidal behavior and insight in adolescents with schizophrenia.
AB  - OBJECTIVES: To investigate the interrelationships between depressive symptoms of
      adolescent schizophrenia, post-psychotic depression (PPD), negative signs,
      suicidal behavior and insights into the disease. METHODS: Three groups of 16
      adolescent inpatients were assessed with regard to: Schizophrenia alone,
      schizophrenia with PPD and major depressive disorder (MDD). The following
      measures were used: DSM IV diagnostic criteria, the Calgary Depression Scale for
      Schizophrenia (CDSS), the PANSS (Positive and Negative Signs of Schizophrenia
      Scale), (BDI) Beck Depression Inventory, (CCL) Cognitive Check List, (HS)
      Hopelessness Scale, (SRS) Suicide Risk Scale, (CSPS) Child Suicide Potential
      Scale and the (SAUMD) Scale to Assess Unawareness of Mental Disorder. RESULTS:
      Compared with MDD adolescents, PPD adolescents showed few somatic and behavioral
      symptoms of depression but had equally severe cognitive and affective depressive
      symptomatology. Suicide risk scores and actual suicidal behavior was prominent in
      PPD adolescents. A positive and significant correlation was found between PPD
      symptoms, suicide risk and awareness of disease (insight). Negative symptoms of
      schizophrenia could be distinguished from PPD symptoms and there was a negative
      correlation between blunted affect and PPD scores. CONCLUSIONS: PPD can be
      diagnosed in adolescent schizophrenia. The symptom pattern is different from MDD,
      therefore, there may be cause to modify DSM IV provisional criteria for this
      condition. Adolescents with schizophrenia who have insight into their illness are
      at higher risk for suicidal behavior and the development of PPD.

PMID- 16604377
TI  - The effect of birth-weight with genetic susceptibility on depressive symptoms in
      childhood and adolescence.
AB  - Low birth-weight has been associated with depression and related outcomes in
      adults, and with problem behaviours in children. This study aimed to examine the
      association between low birth-weight for gestation and depressive symptoms in
      children and adolescents and to examine whether the relationship is moderated by
      genetic risk for depression. An epidemiological, genetically sensitive design was
      used including 2,046 twins aged 8-17 years (1,023 families). Data were obtained
      by parental report and analysed using regression analysis. A small but
      significant association between birth-weight for gestation and early depressive
      symptoms was observed. The unit increase in depressive symptoms per unit decrease
      in birth-weight for gestation was greater for individuals at genetic or familial
      risk for depression. For low birth-weight children, genetic risk for depression
      moderated the influence of birth-weight for gestation in predicting early
      depressive symptoms. Birth-weight for gestation is moderated by genetic and
      familial risk for depression in influencing early depression symptoms. These
      observations have clinical implications in that the impact of being small for
      gestational age on depressive symptoms is greater in children at familial/genetic
      risk although the association between birth weight and depression does not imply
      causality.

PMID- 16604379
TI  - Does pervasive developmental disorder protect children and adolescents against
      drug and alcohol use?
AB  - AIM: The aim of this paper is (1) to compare the rates of reported drug and/or
      alcohol use (DAU) in treatment seeking adolescents with Pervasive Developmental
      Disorders (PDD), and those with other psychiatric diagnoses (psychiatric
      controls) seen in tertiary child and adolescent mental health services and (2) to
      explore the relationship of psychopathology, environmental stressors, and social
      communication difficulties to DAU. METHOD: Data from the chart review of children
      and adolescents aged between 12 and 18 years with psychiatric diagnosis seen in
      tertiary child and adolescent mental health services between 1992 and 2001
      (n=1484) was used to investigate the relationship between DAU, psychopathology,
      environmental stressors and items related to social communication. RESULTS: A
      total of 97 subjects (7%) met criteria for PDD. Subjects with PDD report
      significantly lower DAU than psychiatric controls, 3% vs. 17% respectively
      (P<0.000). Factors reflecting PDD such as speech and language difficulties,
      developmental difficulties, discordant peer relationships in adolescents are
      negatively associated with DAU, while conduct problems, affective symptoms,
      inadequate parental supervision or control have positive association with DAU.
      DAU was present in PDD only when comorbid with Attention Deficit Hyperactivity
      Disorder (ADHD). CONCLUSION: Adolescents with speech and language difficulties,
      developmental difficulties and discordant peer relationships, all reflecting PDD,
      are less likely to have DAU.

PMID- 16604380
TI  - Tear film break-up time evaluated by real-time Hartmann-Shack wavefront sensing.
AB  - PURPOSE: To develop a novel method for measuring tear break-up time (BUT) by
      continuously measuring higher order wavefront aberrations using a Hartmann-Shack
      (H-S) aberrometer. METHODS: Wavefront aberrations up to the sixth order for a 4
      mm pupil were measured in six eyes of six normal subjects using an H-S
      aberrometer. The aberrometry was performed once every second for up to 50 s under
      topical anesthesia. The sequence of the points was divided into two stages, and
      the BUT was defined as the wavefront border of the stages (WFBUT). The WFBUT was
      compared with the BUT by the conventional fluorescein method (FLBUT) or by the
      disruption of placid-ring images (PLBUT). RESULTS: In three eyes, the WFBUT
      (average, 10.9 +/- 1.1 s) was shorter than the PLBUT (average, 17.5 +/- 2.5 s),
      while in the other three eyes the WFBUT (average, 21.5 +/- 2.2 s) was longer than
      PLBUT (average, 8.1 +/- 2.2 s). The FLBUT was shorter than WFBUT or PLBUT in most
      cases. CONCLUSIONS: The tear break-up time measured by H-S aberrometer may be
      used as a practical measure of tear break-up.

PMID- 16604381
TI  - Effects of the matrix metalloproteinase inhibitor GM6001 on the destruction and
      alteration of epithelial basement membrane during the healing of post-alkali burn
      in rabbit cornea.
AB  - PURPOSE: To examine the alteration in structure and matrix composition of
      epithelial basement membrane (BM) during the healing of alkali-burned rabbit
      cornea, and the roles of matrix metalloproteinases (MMPs) in these alterations.
      METHODS: The central cornea of one eye of 78 albino rabbits was exposed to 1 N
      NaOH for 180 s under general and topical anesthesia and allowed to heal with or
      without subconjunctival injection of GM6001 (an MMP inhibitor). Cryosections of
      affected corneas were observed by H&E staining, immunohistochemistry for type IV
      collagen subtypes, or in situ zymography for detection of localization of MMP
      activity. RESULTS: Uninjured corneal epithelial BM exhibited alpha5 (IV)
      immunoreactivity, but lacked the alpha1/alpha2-immunoreactivity of collagen IV.
      Epithelial BM in healing burned cornea transiently exhibited alpha1/alpha2
      immunoreactivity. Examination by in situ zymography showed an upregulation of MMP
      activity in the regenerated central epithelium and anterior stroma of the burned
      corneas at days 7 and 14. GM6001 suppressed degradation of alpha5-containing
      epithelial BM in vivo and also in organ culture. CONCLUSIONS: Epithelial BM was
      degraded by endogenous MMPs during healing following an alkali burn in rabbit
      cornea. GM6001 had an inhibitory effect on the degradation of the epithelial
      basement membrane in burned cornea in vivo.

PMID- 16604382
TI  - Incidence of a latanoprost-induced increase in iris pigmentation in Japanese
      eyes.
AB  - PURPOSE: To prospectively determine the incidence of a latanoprost-induced
      increase in iris pigmentation in Japanese brown iris eyes by identifying changes
      in iris pigmentation on a series of iris color photographs. METHODS: In a cohort
      study, we prospectively and consecutively enrolled 104 patients (104 eyes) with
      primary open-angle glaucoma or normal-tension glaucoma who began treatment with
      latanoprost eye drops for the first time. None of the enrolled patients had a
      history of previous intraocular surgery or laser surgery. Patients comprised 51
      men and 53 women. Their ages ranged from 23 to 80 years (mean +/- SD, 63.8 +/-
      10.4 years). Before and every 3 months after starting latanoprost treatment, iris
      photographs were taken using a slit-lamp biomicroscope with an attached camera.
      To identify an increase in iris pigmentation, seven glaucoma specialists
      independently read the series of photographs. If five of the seven observers
      agreed that iris pigmentation had increased, we determined that the iris
      pigmentation had increased from the time the previous photograph was taken. Ten
      normal volunteers served as controls, and photographs of their eyes were used in
      the evaluation of iris pigmentation. The Kaplan-Meier life table analysis was
      adopted to evaluate the incidence of increase in iris pigmentation during
      treatment with latanoprost. RESULTS: The Kaplan-Meier life table analysis
      indicated that the incidence of increased iris pigmentation at 3, 6, 9, 12, and
      15 months after the start of latanoprost treatment was 16.3%, 34.2%, 49.5%,
      58.2%, and 58.2%, respectively. CONCLUSIONS: Latanoprost instillation for at
      least 1 year induced increased iris pigmentation in approximately 50% of the
      treated Japanese eyes, which is a considerably higher percentage than that
      reported in Caucasians.

PMID- 16604383
TI  - Lacrimal gland choristoma of the ciliary body.
AB  - BACKGROUND: Lacrimal gland choristoma manifesting in the ciliary body is quite
      rare. We report a case of lacrimal gland choristoma manifesting in the ciliary
      body, coupled with orbital cellulites, in an infant. CASE: A 10-month-old female
      infant with swelling and tenderness of the right upper eyelid. OBSERVATIONS: The
      results of ophthalmic examinations of the patient were consistent with orbital
      cellulitis. During the funduscopic examination, a fleshy mass was incidentally
      detected at the superotemporal portion of the ciliary body in the right eye. A
      local resection of the lesion was carried out. The results of a pathologic
      examination showed lacrimal gland choristoma of the ciliary body that was
      accompanied by an epithelia-lined cyst. The patient has had no hypotonia or
      enlargement of the lesion for 1 year after surgery. CONCLUSION: Lacrimal gland
      choristoma should be included in the differential diagnosis of a ciliary body
      mass in pediatric patients.

PMID- 16604384
TI  - Systemic T cell response to Toxoplasma gondii antigen in patients with ocular
      toxoplasmosis.
AB  - PURPOSE: Analysis of systemic cellular response to Toxoplasma antigen in patients
      with ocular toxoplasmosis. METHODS: Activated (CD25(+)) T cells were detected by
      flow cytometry after a 7-day culture of whole blood from patients with ocular (n
      = 16) or asymptomatic (n = 14) toxoplasmosis, and controls (n = 10), in the
      presence of soluble Toxoplasma antigen (ST-Ag). Interferon (IFN)-gamma,
      interleukin (IL) 4, and IL-10 were measured in culture supernatants by enzyme
      linked immunosorbent assay. RESULTS: Higher percentages of CD25(+) T cells were
      detected in ST-Ag-activated cultures from Toxoplasma-infected patients, with or
      without ocular lesions (37.0 +/- 19.1% or 41.1 +/- 19.3%, respectively) than from
      controls (3.2 +/- 1.2%) (P < 0.0001). Differences were not statistically
      significant between asymptomatic and ocular toxoplasmosis (P > 0.4) or among
      congenital, acquired, and undetermined ocular toxoplasmosis (P > 0.2). Higher
      levels of IFN-gamma were detected in ST-Ag-stimulated blood cultures from
      infected patients than in those from controls (P < 0.0001), with no difference
      between patients with asymptomatic or ocular toxoplasmosis (P > 0.05). IL-10 was
      detected only in activated culture supernatants from three patients with ocular
      toxoplasmosis and two patients with asymptomatic toxoplasmosis. IL-4 was never
      produced in ST-Ag-activated cultures. CONCLUSIONS: Systemic cellular response to
      ST-Ag does not differ between the patients with ocular and asymptomatic
      toxoplasmosis with regard to activation markers and type 1 cytokine production.

PMID- 16604385
TI  - A microperimeter that provides fixation pattern and retinal sensitivity
      measurement.
AB  - PURPOSE: To investigate a microperimeter (MP-1) that can independently measure
      fixation status and microperimetry of retinal threshold sensitivity by comparing
      the results obtained by the MP-1 with those obtained by scotometry using scanning
      laser ophthalmoscopy (SLO). METHODS: Fourteen patients (15 eyes) with a macular
      disorder were examined by the MP-1 fixation test, MP-1 microperimetry, and SLO
      scotometry. The scotoma size seen in MP-1 microperimetry was compared with that
      observed in SLO scotometry. The location of the preferred retinal locus (PRL) and
      the fixation stability, which were obtained from the fixation test in MP-1, were
      also compared with those obtained in SLO scotometry. RESULTS: The scotoma size,
      which was not seen with 0 dB in MP-1 microperimetry, was larger than that in SLO
      scotometry in 8 of the 15 eyes. Retinal threshold sensitivity decreases were
      found using MP-1 microperimetry within a sensitive area of SLO scotometry in all
      eyes. The PRL in the MP-1 fixation test and in SLO scotometry agreed in all eyes.
      Fixation stability in the MP-1 fixation test significantly correlated with that
      in SLO scotometry (P = 0.0192). CONCLUSIONS: The results of MP-1 microperimetry
      do not completely agree with those of SLO scotometry owing to the difference in
      stimulus intensity. The MP-1 fixation test is useful for measuring PRL and
      fixation stability in a short time. MP-1 might be helpful to evaluate the foveal
      function in patients with macular disorders without severely damaged macular
      function.

PMID- 16604386
TI  - Expression of pigment epithelium-derived factor and vascular endothelial growth
      factor in fibrovascular membranes from patients with proliferative diabetic
      retinopathy.
AB  - PURPOSE: The expression of pigment epithelium-derived factor (PEDF), a strong
      inhibitor of angiogenesis, has not been examined in human ocular fibrovascular
      membranes, to the best of our knowledge. The purpose of this study was to
      determine whether PEDF is expressed in the fibrovascular membranes in eyes of
      patients with proliferative diabetic retinopathy (PDR), and to compare the
      expression of PEDF with that of vascular endothelial growth factor (VEGF).
      METHODS: The expression of PEDF and VEGF in the fibrovascular membranes excised
      during vitreous surgery in eight cases of PDR was determined by
      immunohistochemistry. RESULTS: VEGF was strongly expressed in the endothelial
      cells of newly formed vessels in the fibrovascular membranes. In contrast, PEDF
      was weakly expressed in the endothelial cells and was prominently expressed in
      the extracellular matrix and fibrous tissue surrounding the new vessels.
      CONCLUSIONS: Our results suggest that PEDF, along with VEGF, may modulate the
      formation of fibrovascular membranes in patients with PDR.

PMID- 16604387
TI  - Expression of c-Jun and Bcl-2 family proteins in apoptotic photoreceptors of RCS
      rats.
AB  - PURPOSE: To determine if c-Jun and Bcl-2 family proteins play a role in
      photoreceptor apoptosis in Royal College of Surgeons (RCS) rats. METHODS: RCS and
      Sprague-Dawley rats were used. Cryosections of retinas harvested at various
      postnatal periods were immunostained with antibodies against c-Jun, Bcl-2, and
      Bax. Double staining with TdT-dUTP nick-end labeling (TUNEL) or propidium iodide
      (PI) and antibodies was also done. To study the time course of gene and protein
      expression, semiquantitative reverse transcriptase-polymerase chain reaction (RT
      PCR) and immunoblotting analyses were carried out. RESULTS: TUNEL-positive
      photoreceptors of RCS rats were stained strongly with antibodies against c-Jun
      and Bax. The number of immunoreactive cells increased on days 21 and 28 after
      birth (P21 and P28) and decreased on P45. Semiquantitative RT-PCR analysis showed
      that mRNAs for c-Jun and Bax were upregulated at P21 and P28, but those for Bcl-2
      were unchanged. On immunoblotting, a 43-kDa band was revealed by the anti-c-Jun
      antibody and a 21-kDa band, by the anti-Bax antibody. Protein expression of c-Jun
      and Bax were increased at both P21 and P28. The temporal profiles of
      immunoreactivity, protein expression, and mRNA expression were similar.
      CONCLUSION: c-Jun and Bax may play a role in photoreceptor apoptosis in RCS rats.

PMID- 16604388
TI  - Mitochondrial DNA mutations with Leber's hereditary optic neuropathy in Japanese
      patients with open-angle glaucoma.
AB  - PURPOSE: Abnormal optic disc excavations are found in patients with Leber's
      hereditary optic neuropathy (LHON). The purpose of this study was to determine
      whether heteroplasmy for the major three LHON mutations or for the rare LHON
      mutations are risk factors for open-angle glaucoma. METHODS: Blood samples from
      835 Japanese subjects were screened with the Invader assay for ten LHON
      associated mutations: three major mutations (G3460A, G11778A, T14484C) and seven
      rare mutations (T9101C, G9804A, C14482A, C14482G, G14459A, T14498C, and A14510G).
      Of the 835 subjects, 241 were patients with primary open-angle glaucoma (POAG),
      310 were patients with normal-tension glaucoma (NTG), and 284 were healthy
      controls. RESULTS: Five POAG patients and three NTG patients had one of five
      mutations, C9099A, T9101G, T9101C, G9804A, or G11778A, but none of these patients
      had LHON. The C9099A (Ile191Met) and T9101G (Ile192Ser) mutations were novel and
      identified within the probes by lack of signal in the assay. Two patients with
      the G11778A mutation showed heteroplasmy, with 15% mutant mtDNA in the male
      patient and 80% in the female patient. The remaining LHON-associated mutations
      were not detected in any of the subjects. A case-control study did not show a
      significant difference (P = 0.099): eight potentially disease-associated variants
      in 551 patients versus zero variants in the 284 controls. CONCLUSIONS: Rare LHON
      associated mitochondrial DNA mutations were found in Japanese patients with open
      angle glaucoma (OAG). However, whether mitochondrial DNA mutations are risk
      factors for OAG is still open to question.

PMID- 16604389
TI  - Intraoperative quantification using finger force for involutional blepharoptosis
      without postoperative lagophthalmos.
AB  - PURPOSE: To report intraoperative quantification using finger force for
      involutional blepharoptosis, which helps in the prevention of postoperative
      lagophthalmos. METHODS: We carried out levator resection on 20 involutional
      blepharoptic eyelids. Fissure height was examined intraoperatively to evaluate
      the extent of resection. If a patient presented more than 3 mm of lagophthalmos
      in voluntary eyelid closure but could fully open the eye, we forcibly closed the
      eyelid, using a finger, after voluntary eyelid closure. If more than 3 mm of
      lagophthalmos was still observed after forced eyelid closure, we corrected eyelid
      tension until lagophthalmos became less than 2 mm. RESULTS: Six of the ten
      patients (20 eyelids) presented with full eyelid opening but more than 3 mm of
      lagophthalmos in voluntary eyelid closure. After the upper eyelids were forcibly
      lowered, all six eyelids showed less than 2 mm of lagophthalmos. There were no
      cases of lagophthalmos 1 month postoperatively. CONCLUSIONS: Additional finger
      force makes precise quantification of blepharoptosis surgery possible and
      prevents postoperative lagophthalmos.

PMID- 16604390
TI  - Endoscopy-guided transcaruncular Jones tube intubation without
      dacryocystorhinostomy.
AB  - PURPOSE: To evaluate the functional surgical success, complications, and degree
      of satisfaction after endoscopy-guided transcaruncular Jones tube intubation
      without dacryocystorhinostomy (DCR). METHODS: A pair of Westcott scissors was
      passed into the nose from the side of the caruncle, and the lacrimal bone was
      penetrated between the lacrimal sac and the nasal mucosa. After the proper length
      of Jones tube was decided, the tube was inserted into the nasal cavity and fixed
      at the caruncle with nonabsorbable suture material. This procedure was done
      without DCR. We retrospectively reviewed the 60 patients (70 eyes) with
      canalicular obstruction who underwent Jones tube intubation in this manner.
      RESULTS: The overall success rate was 91.4%. The length of Jones tube used ranged
      from 16 to 30 mm. Retrograde air blowing into the eye via the Jones tube was the
      most common complaint (25 of 70 eyes). Complications of this technique included
      tube problems (25.7%), in particular, downward displacement (22.9%), which was
      corrected easily in the outpatient clinic, and extrusion. Other complications
      were frequent inflammation and conjunctival growth over the tube opening.
      CONCLUSIONS: Endoscopy-guided Jones tube intubation without DCR is a simple and
      useful procedure for correcting canalicular obstruction.

PMID- 16604391
TI  - Relationship between corneal aberrations and contrast sensitivity after hyperopic
      laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the relationship between corneal aberrations and contrast
      sensitivity (CS) after hyperopic laser in situ keratomileusis (H-LASIK). METHODS:
      In 13 patients (13 eyes) who underwent H-LASIK, we measured CS and corneal
      topography preoperatively and at 1 year postoperatively. Photopic and scotopic CS
      values were measured at 3, 6, and 12 cycles/degree (cpd) using an MCT-8000
      contrast tester. Corneal aberrations were determined from the data on corneal
      topography using CTView. The corneal high-order aberrations were defined as the
      sum of the third- and fourth-order aberrations in the 4-mm zone and the sum of
      the third- to sixth-order aberrations in the 6-mm-zone. RESULTS: Under scotopic
      conditions at 12 cpd, the changes in CS significantly correlated with changes in
      the corneal aberrations. Scotopic CS was significantly deteriorated by glare, but
      photopic CS was not significantly changed. H-LASIK induced a significant increase
      in corneal aberrations that positively correlated with the amount of correction,
      regardless of the improvement in logMAR corrected visual acuity. LogMAR corrected
      visual acuity did not significantly correlate with corneal aberrations.
      Furthermore, decentration significantly correlated with the changes in the 6-mm
      zone corneal aberrations. CONCLUSIONS: In eyes after H-LASIK, the changes in
      scotopic CS significantly correlated with those in the corneal aberrations, which
      might have resulted from decentration or ablation profiles in H-LASIK and a
      relatively small optical zone. Further studies will be needed to validate this
      relationship.

PMID- 16604392
TI  - Latanoprost nonresponders with open-angle glaucoma in the Japanese population.
AB  - PURPOSE: As some patients show little response to latanoprost, one of the most
      powerful topical glaucoma medications, we investigated the incidence and clinical
      profiles of latanoprost nonresponders (LNR) in the Japanese population. METHODS:
      We examined 62 glaucoma patients (62 eyes) who had received only latanoprost for
      more than 3 months. Their mean age was 63.8 +/- 1.8 years; the mean observation
      period was 9.7 +/- 0.4 months. At 1, 3, 6, and 12 months, their intraocular
      pressure (IOP) was measured, and the IOP reduction rate (RR) and the rate of LNR,
      defined as RR of 10% or less, were calculated. We statistically analyzed clinical
      factors involved in the LNR status of our study population. RESULTS: At 1, 3, 6,
      and 12 months, RR was 20.1 +/- 2.0%, 18.8 +/- 2.3%, 21.1 +/- 2.8%, and 23.0 +/-
      2.6%, respectively. At the same time points, the LNR incidence was 23.1%, 28.1%,
      23.5%, and 31.8%, respectively, and significantly higher in patients whose
      baseline IOP was less than 15 mmHg. Patient sex and age and the glaucoma type
      played no significant role in the LNR status. CONCLUSIONS: The incidence of LNR
      in the Japanese population, including normal-tension glaucoma (NTG) patients, is
      higher than among European or American patients. Only low baseline IOP was a
      significant clinical factor among LNR.

PMID- 16604393
TI  - Visual field defect after radial optic neurotomy for central retinal vein
      occlusion.
AB  - PURPOSE: To evaluate visual field defects after radial optic neurotomy (RON) in
      eyes with central retinal vein occlusion (CRVO). METHODS: Eight patients (eight
      eyes) underwent RON for macular edema associated with CRVO. Goldmann perimetry
      was performed on each patient both before and after surgery. RESULTS:
      Postoperative Goldmann perimetry showed a temporally located wedge-shaped visual
      field defect consistent with neural damage secondary to RON in seven eyes (88%).
      After surgery, the visual field decreased from preoperative values by 7% at 3
      months (P = 0.30) and by 21% at 12 months (P = 0.0023). Although three patients
      (38%) were aware of the postoperative visual field defect, only one patient (13%)
      considered this defect to be a visual disability. CONCLUSIONS: After RON, most
      patients showed a postoperative defect in the temporal visual field consistent
      with the incision to the optic disk. However, this visual field defect appears to
      be well tolerated by most patients.

PMID- 16604394
TI  - Photodynamic therapy in macular diseases of asian populations: when East meets
      West.
AB  - PURPOSE: We reviewed the indications, safety, and efficacy of photodynamic
      therapy with verteporfin in various macular diseases and vasculopathies, which
      are common in Asian populations, and compared the outcomes of photodynamic
      therapy in Asian patients with the outcomes in Caucasian patients. METHODS:
      Relevant clinical and laboratory original articles, case reports, and review
      articles that have been published in the literature between January 1999 and
      October 2004 were searched in Medline. The potential differences in the response
      to photodynamic therapy between Asian and Caucasian patients were evaluated.
      Articles in foreign languages with English abstracts were included. RESULTS:
      Macular diseases commonly seen in Asian populations, including choroidal
      neovascularization (CNV) of age-related macular degeneration, secondary to
      pathologic myopia or from an idiopathic cause, and choroidal vasculopathies such
      as central serous chorioretinopathy and polypoidal choroidal vasculopathy were
      included in the review. The results were tabulated and the differences with
      Caucasian populations were compared and highlighted. CONCLUSION: Photodynamic
      therapy has been found to be an effective and noninvasive treatment for various
      subfoveal CNV and choroidal vasculopathies of the macula. Diverse behavior in
      different ethnic groups is observed.

PMID- 16604395
TI  - Low conversion rate to multiple sclerosis in idiopathic optic neuritis patients
      in Taiwan.
AB  - PURPOSE: To investigate the clinical characteristics of patients with idiopathic
      optic neuritis (ON) in Taiwan and to assess the conversion rate to multiple
      sclerosis (MS) in these patients. METHODS: We studied the medical records of a
      total of 109 patients with a clinical diagnosis of idiopathic ON treated in the
      Taipei Veterans General Hospital during the period from January 1986 to May 2003.
      Clinical characteristics, management, and disease courses were retrospectively
      reviewed. Our main focus was on the development of multiple sclerosis after an ON
      attack. Univariate and multivariate analyses were used to evaluate the risk
      indicators for MS conversion. RESULTS: The patients (58 women, 51 men) had a mean
      age of 41.2 years at onset. ON was retrobulbar in 46.8% of the patients.
      Management with or without pulse therapy did not affect the final visual outcome.
      Female sex, retrobulbar type ON, recurrent cases, elevated cerebrospinal fluid
      (CSF) IgG index, and central nervous system (CNS) imaging abnormalities were
      identified as risk indicators for the development of MS (P < 0.05). The 2-year
      cumulative probability of developing MS was 5.92%, and the 5-year cumulative
      probability was 14.28%. The conversion rate to MS did not differ among treatment
      groups. CONCLUSIONS: Idiopathic ON patients in Taiwan have an older age at onset
      and a higher percentage of optic disc edema than reported in previous literature.
      The characteristic features of ON patients associated with a high risk of
      developing MS are female sex, retrobulbar type ON, CNS imaging abnormalities,
      elevated CSF IgG index, and recurrence. Idiopathic ON patients in Taiwan display
      a significantly lower conversion rate to MS.

PMID- 16604396
TI  - External ophthalmomyiasis infestation.

PMID- 16604397
TI  - Secondary unilateral glaucoma and neuroretinitis: atypical manifestation of cat
      scratch disease.

PMID- 16604398
TI  - Null ABCA4 gene mutations found in Japanese patients with panretinal
      degeneration.

PMID- 16604399
TI  - A case of idiopathic retinal vasculitis, aneurysm, and neuroretinitis effectively
      treated by steroid pulse therapy.

PMID- 16604400
TI  - Diagnosis of atypical choroidal malignant melanoma using N-isopropyl-p-[123I]
      iodoamphetamine single photon emission computed tomography.

PMID- 16604401
TI  - Porous polyethylene implants in orbital floor reconstruction.

PMID- 16604402
TI  - Primary intraosseous orbital hemangioma of the lacrimal bone.

PMID- 16604403
TI  - Bilateral renal vein thrombosis secondary to membraneous glomerulonephritis:
      successful treatment with thrombolytic therapy.
AB  - Renal vein thrombosis (RVT) is a rare phenomenon. Bilateral RVT is even less
      common. RVT has been reported as idiopathic or in association with puerperium,
      hypercoagulable states, membraneous glomerulonephritis (MGn), renal
      transplantation, malignancy, and renal vein instrumentation or trauma. Due to its
      rarity, the literature describing RVT consists mainly of isolated case reports
      and there are no consistent recommendations regarding diagnosis and treatment of
      this vascular emergency. We present a case of bilateral RVT associated with MGn.
      A 45-year-old man complaining of nonspecific abdominal pain of 2 days' duration
      was found to have bilateral RVT upon computed tomographic evaluation. He was
      successfully treated with emergent endovascular mechanical thrombectomy in
      conjunction with chemical thrombolysis and subsequently therapeutically
      anticoagulated. A renal biopsy demonstrated MGn, and the patient was placed on an
      appropriate medical regimen. He is well approximately 18 months later, with
      preserved renal function. Despite a multitude of potential causative mechanisms,
      all RVT patients should undergo a thorough workup for underlying hypercoagulable
      disorder and underlying benign or malignant renal causes. Treatment is aimed at
      prompt relief of venous obstruction and preservation of renal parenchymal
      function. Interventional radiological procedures, including thrombolysis and
      thrombectomy, have proven to be valuable in the treatment of RVT. Surgical
      options include thrombectomy and nephrectomy.

PMID- 16604404
TI  - A simple DSA method to detect air contamination during CO2 venous studies.
AB  - The use of CO2 as a contrast agent has increased significantly for visualization
      of the central veins, inferior vena cava, and portal vein. The most serious
      complication associated with CO2 studies is air contamination. We evaluated a
      simple digital subtraction angiogram (DSA) method to detect air contamination
      during CO2 venous studies. After injections of 5, 10, and 20 cm3 of CO2 and 5 cm3
      of air into the inferior vena cavas of five domestic swine in the left lateral
      decubitus position, a DSA was performed using the cross-table lateral projection
      to visualize the gases trapped in the right atrium. The time to complete
      dissolution of CO2 at increased doses was compared to that of air. Vital signs
      were observed during and after CO2 or air injection. In all animals, DSA showed
      the trapped gas outlining the wall of the right atrium. Five cubic centimeters of
      CO2 was cleared from the right atrium in an average of 46 sec (21-60 sec),
      whereas 5 cm3 of air remained visible over 5 min. Ascending doses of CO2
      increased the time of dissolution to 54 sec (47-67 sec) for 10 cm3 and 70 sec (45
      90 sec) for 45 cm3. Vital signs remained stable during the study. Using DSA, CO2
      can be distinguished from air by demonstrating rapid absorption of the former,
      thus allowing detection of air contamination during CO2 venous studies. If the
      gases trapped in the right atrium remain visible 90 sec after the injection, air
      contamination should be suspected.

PMID- 16604405
TI  - Percutaneous vertebroplasty in a broken vertebral titanium implant (titanium mesh
      cage).
AB  - We report the case of a percutaneous consolidation of a broken vertebral implant
      (Surgical Titanium Mesh Implants; DePuy Spine, Raynham, MA, USA) by
      vertebroplasty. Four years after anterior spondylectomy with cage implantation
      and stabilization with posterior instrumentation, the patient was admitted for
      excruciating back pain. Radiographs showed fracture of the cage, screw, and rod.
      An anterior surgical approach was deemed difficult and a percutaneous injection
      of polymethyl methacrylate into the cage was performed following posterior
      instrumentation replacement. This seems to be an interesting alternative to the
      classical anterior surgical approach, which is often difficult in postoperative
      conditions.

PMID- 16604406
TI  - Iatrogenic iliac artery rupture: emergency management by longer stent-graft on a
      shorter balloon.
AB  - Rupture of an iliac artery during percutaneous transluminal coronary angioplasty
      is a rare but potentially devastating complication. We report a case of
      iatrogenic external iliac artery rupture that was successfully treated by
      temporary balloon occlusion followed by endovascular stent graft placement in an
      unusual manner. Limited availability of the hardware necessitated the use of a
      longer bare stent graft mounted on a relatively shorter balloon.

PMID- 16604407
TI  - Potential air contamination during CO2 angiography using a hand-held syringe:
      theoretical considerations and gas chromatography.
AB  - PURPOSE: To assess air contamination in the hand-held syringes currently used for
      CO2 delivery and to determine whether there is an association between their
      position and the rate of air contamination. METHODS: Assessment of air
      contamination in the syringe (20 ml) included theoretical modeling, mathematical
      calculation, and gas chromatography (GC). The model was used with Fick's first
      law to calculate the diffusion of CO2 and the amount of air contamination. For GC
      studies, the syringes were placed in the upright, horizontal, and inverted
      positions and gas samples were obtained after 5, 10, 20, 30, and 60 min. All
      trials with each position for each sampling time were performed five times.
      RESULTS: The amounts of air contamination with time calculated mathematically
      were 5-10% less than those of GC. With the diffusivity of air-CO2 at 0.1599
      cm2/sec (9.594 cm2/min), air contamination was calculated to be 60% at 60 min.
      With GC air contamination was 13% at 5 min, 31% at 20 min, 43% at 30 min, and 68%
      at 60 min. There was no difference in air contamination between the different
      syringe positions. CONCLUSION: Air contamination occurs in hand-held syringes
      filled with CO2 when they are open to the ambient air. The amounts of air
      contamination over time are similar among syringes placed in the upright,
      horizontal, and inverted positions.

PMID- 16604408
TI  - An unusual aneurysm of the main pulmonary artery presenting as acute coronary
      syndrome.
AB  - A 70-year old man presented with retrosternal chest pain. His electrocardiogram
      showed nonspecific T wave changes. Cardiac-specific troponin I (cTnI) was
      elevated. His condition was managed as acute coronary syndrome, following which
      he had two minor episodes of hemoptysis. A CT pulmonary angiogram showed no
      evidence of pulmonary embolism, but a large mass lesion was seen in the
      mediastinum. Echocardiography and cardiac MRI demonstrated a large solid mass,
      arising from the right ventricular outflow tract and causing compression of the
      main pulmonary artery (MPA). The differential diagnosis included pericardial and
      myocardial tumors and clotted aneurysm of the MPA. At surgery, a clotted
      aneurysmal sac was identified originating from the MPA and the defect was healed.
      Aneurysms of the MPA are rare. They most commonly present with dyspnea and chest
      pain. Compression of surrounding structures produces protean manifestations. A
      high index of suspicion coupled with imaging modalities establishes the
      diagnosis. Blunt trauma to the chest, at the time of an accident 4 years
      previously, may explain this aneurysm. The patient's presentation with chest pain
      was probably due to compression and/or stretching of surrounding structures.
      Coronary artery compression simulating acute coronary syndrome has been
      documented in the literature. The rise in cTnI may have been due to right
      ventricular strain, as a result of right ventricular outflow obstruction by the
      aneurysm. This has not been reported previously in the literature. The saccular
      morphology and narrow neck of the aneurysm predisposed to stagnation leading to
      clotting of the lumen and healing of the tear, which caused the diagnostic
      difficulty.

PMID- 16604409
TI  - Right ventricular migration of a recovery IVC filter's fractured wire with
      subsequent pericardial tamponade.
AB  - A Recovery filter (C.R. Bard, Tempe, AZ, USA) is a device for pulmonary embolism
      prophylaxis. There have been few case reports involving the migration of this
      particular filter or of a broken wire migrating to the heart. We report a case of
      right ventricular migration of a fractured wire from this filter in a patient who
      subsequently developed pericardial tamponade and required open heart surgery to
      extract the fractured wire. We discuss the current US Food and Drug
      Administration (FDA)-approved nonpermanent inferior vena cava filters and their
      reported complications. These complications can be life-threatening and may
      require immediate surgical intervention.

PMID- 16604410
TI  - Use of stent grafts for infected mycotic aneurysms.

PMID- 16604411
TI  - Postprocedural aspiration test to predict adequacy of dialysis following tunneled
      catheter placement.
AB  - The objective of the study was to determine if a timed aspiration technique with
      a 20-ml syringe can be used to predict adequacy of blood flow in tunneled
      dialysis catheters. Sixteen patients referred for de novo placement or
      manipulation of failing tunneled hemodialysis catheters had the time it takes to
      fill a 20-ml syringe with the plunger fully withdrawn measured to the nearest
      tenth of a second. These measurements were correlated with flow rates recorded in
      dialysis just prior to (if failed catheter) and in the following dialysis session
      with adequacy determined as at least 300 ml/min. Syringe-filling time (22
      catheters in 16 patients) was plotted against adequacy of dialysis. The mean time
      to fill a 20-ml syringe was 2.2 sec, with a range of 1.0-4.7 sec. The mean time
      to fill syringes for catheters with adequate dialysis was 1.7 +/- 0.5 sec, and
      for inadequate catheters, it was 2.8 +/- 0.8 sec. These differences are
      statistically significant (p < 0.001). Using a filling time of greater than or
      equal to 2 sec as a threshold gives the highest sensitivity (100%) for predicting
      inadequate dialysis while maintaining high specificity (75%). To achieve a
      specificity of 100%, a 3-sec cutoff would be necessary, but would lead to a
      sensitivity of only 20%. A simple and objective aspiration technique can be
      performed at the time of tunneled dialysis catheter placement/manipulation to
      reasonably predict adequacy of subsequent dialysis.

PMID- 16604412
TI  - CT-guided percutaneous thrombin injection for treatment of an inferior
      pancreaticoduodenal artery pseudoaneurysm.
AB  - We present a case of an inferior pancreaticoduodenal artery pseudoaneurysm
      treated by computed tomography (CT)-guided percutaneous injection of thrombin. As
      far as we are aware, we present the first documented case of successful long-term
      (9 months) follow-up with no evidence of recurrence.

PMID- 16604413
TI  - Life-threatening hematuria requiring transcatheter embolization following
      radiofrequency ablation of renal cell carcinoma.
AB  - Radiofrequency ablation is increasingly being acknowledged as a valid treatment
      for renal cell carcinoma in patients in whom definitive curative resection is
      deemed either undesirable or unsafe. A number of published series have shown the
      technique to have encouraging results and relatively low complication rates. In
      this article, we report a case of delayed life-threatening hematuria requiring
      transcatheter embolization of a bleeding intrarenal artery in a patient who had
      undergone imaging-guided radiofrequency ablation of a 3 cm renal cell carcinoma.
      To our knowledge, such a complication has not been reported previously.

PMID- 16604414
TI  - Descending tumor thrombus from renal cell carcinoma metastases with SVC syndrome.
AB  - We describe a case of renal cell carcinoma metastases to the thyroid gland
      invading local veins and extending to the neck veins causing superior vena cava
      (SVC) syndrome.

PMID- 16604415
TI  - A proteomic approach towards the analysis of salt tolerance in Rhizobium etli and
      Sinorhizobium meliloti strains.
AB  - Soluble proteins from the salt-tolerant Rhizobium etli strain EBRI 26 were
      separated by two-dimensional (2D) gel electrophoresis and visualised by Commassie
      staining. Six proteins are highly expressed after induction by 4% NaCl compared
      to the non-salt-stressed cells. These proteins have pI between 5 and 5.5 and
      masses of approximately 22, 25, 40, 65, 70, and 95 kDa. These proteins were
      analysed by Matrix-assisted laser adsorption ionization time of flight (MALDI
      TOF) after digestion with trypsin. Despite having very good peptide mass
      fingerprint data, these proteins could not be identified, because the genome
      sequence of R. etli is not yet published. In a second approach, soluble proteins
      from salt-induced or non-salt-induced cultures from R. etli strain EBRI 26 were
      separately labelled with different fluorescent cyano-dyes prior to 2D difference
      in gel electrophoresis. Results revealed that 49 proteins are differentially
      expressed after the addition of sodium chloride. Fourteen proteins are
      overexpressed and 35 were downregulated. The genome of Sinorhizobium meliloti, a
      closely related species to R. etli, has been published. Similar experiments using
      Sinorhizobium meliloti strain 2011 identified four overexpressed and six
      downregulated proteins. Among the overexpressed protein is a carboxynospermidin
      decarboxylase, which plays an important role in the biosynthesis of spermidin
      (polyamine). The enzyme catalase is among the downregulated proteins. These
      proteins may play a role in salt tolerance.

PMID- 16604416
TI  - Degradation of plasticizer di-n-butylphthalate by Delftia sp. TBKNP-05.
AB  - Bacterial strain Delftia sp. TBKNP-05, isolated by para-hydroxybenzoate
      enrichment technique, is capable of degrading di-n-butylphthalate (DBP) as a sole
      source of carbon and energy. Analysis of intermediates by thin-layer
      chromatography and high-performance liquid chromatography indicated the presence
      of monobutylphthalate (MBP), phthalate (PA), and protocatechuate (PCA). The
      washed cells grown on DBP and PA showed appreciable oxidation of DBP, MBP, PA,
      and PCA. The enzyme activities in cell-free extracts of Delftia sp. TBKNP-05
      exhibited the presence of DBP esterase, MBP esterase, PA-dioxygenase, and PCA 4,5
      dioxygenase. The PCA is metabolized by meta-cleavage pathway, leading to further
      mineralization of the compound in this bacterium.

PMID- 16604417
TI  - Ammonium toxicity in bacteria.
AB  - Although an excellent nitrogen source for most bacteria, ammonium was-in analogy
      to plant and animal systems-assumed be detrimental to bacteria when present in
      high concentrations. In this study, we examined the effect of molar ammonium
      concentrations on different model bacteria, namely, Corynebacterium glutamicum,
      Escherichia coli, and Bacillus subtilis. The studied bacteria are highly
      resistant to ammonium. When growth was impaired upon addition of molar (NH4)2SO4
      concentrations, this was not caused by an ammonium-specific effect but was due to
      an enhanced osmolarity or increased ionic strength of the medium. Therefore, it
      was concluded that ammonium is not detrimental to C. glutamicum and other
      bacteria even when present in molar concentrations.

PMID- 16604418
TI  - Plant growth-promoting Pseudomonas sp. Strains reduce natural occurrence of
      anthracnose in soybean (Glycine max L.) in central Himalayan region.
AB  - Biological control is an accepted important component of current plant disease
      management strategies. Introduction of bacterized seeds carrying bacterial
      isolates with proven growth-promotion capabilities and antagonistic
      characteristics offer a valid alternative to chemical protectants. Root
      colonization of disease-susceptible (PS 1024) and moderately resistant (PS1042)
      varieties of soyabean (Glycine Max L) by fluorescent pseudomonad (FLPs) strains
      GRP3, PEn-4, PRS1, and WRS-24 was studied in relation to natural occurrence of
      anthracnose caused by Colletotrichum dematium (Pers Ex Fr.) Grove. Rhizoplane
      population of FLPs was maintained at a critical level (5.3 cfu) up to 30 days of
      plant growth, followed by a steep decline. Indigenous FLPs population, however,
      remained nearly unchanged (3.0 to 2.4 log g(-1) root) between 30 days and 75 days
      of plant growth. The relative FLPs population in rhizosphere was lower than that
      in rhizoplane. Although intervarietal difference was observed, the root/shoot
      length remained unaffected. Compared to nonbacterized control, dry root weight
      was improved by FLPs treatment. Severity of foliar anthracnose was reduced
      significantly after FLPs treatment in the variety PS 1042. Because the point of
      FLPs treatment (seed bacterization) was away from the site of disease appearance
      (leaf), operation of induced systemic resistance in strains PEn-4 and GRP3
      appears imminent.

PMID- 16604419
TI  - Diverse UV-B resistance of culturable bacterial community from high-altitude
      wetland water.
AB  - Isolation of most ultraviolet B (UV-B)-resistant culturable bacteria that occur
      in the habitat of Laguna Azul, a high-altitude wetland [4554 m above sea level
      (asl)] from the Northwestern Argentinean Andes, was carried out by culture-based
      methods. Water from this environment was exposed to UV-B radiation under
      laboratory conditions during 36 h, at an irradiance of 4.94 W/m2. It was found
      that the total number of bacteria in water samples decreased; however, most of
      the community survived long-term irradiation (312 nm) (53.3 kJ/m2). The
      percentage of bacteria belonging to dominant species did not vary significantly,
      depending on the number of UV irradiation doses. The most resistant microbes in
      the culturable community were Gram-positive pigmented species (Bacillus
      megaterium [endospores and/or vegetative cells], Staphylococcus saprophyticus,
      and Nocardia sp.). Only one Gram-negative bacterium could be cultivated
      (Acinetobacter johnsonii). Nocardia sp. that survived doses of 3201 kJ/m2 were
      the most resistant bacteria to UV-B treatment. This study is the first report on
      UV-B resistance of a microbial community isolated from high-altitude extreme
      environments, and proposes a method for direct isolation of UV-B-resistant
      bacteria from extreme irradiated environments.

PMID- 16604420
TI  - Production of alkaline lipase by Corynebacterium paurometabolum, MTCC 6841
      isolated from Lake Naukuchiatal, Uttaranchal State, India.
AB  - A moderately psychrophilic bacterium Corynebacterium paurometabolum MTCC 6841
      (gram positive, short rod type) producing extracellular alkaline lipase was
      isolated from Lake Naukuchiatal, Uttaranchal, India. The bacterium was able to
      grow within a broad range of pH (5-10). Soyabean oil and olive oil served as the
      best carbon sources for lipase production. The bacterium preferred inorganic
      nitrogenous compounds, NaNO3 and KNO3, over organic nitrogenous compound for its
      growth. Maximum lipase production occurred at 25 degrees C and 8.5 pH. The enzyme
      activity was found to be maximum at the same values of temperature and pH. The
      enzyme was reasonably stable in the presence of various organic solvents. No
      significant effect of Ca+, Cu++, Fe++, Na+, K+, Mg++, Mn+, NH4+, Co++ ions over
      enzyme activity was detected. Treatment with EDTA reduced the activity to nearly
      one half.

PMID- 16604421
TI  - Anti-fibrotic effects of thalidomide on hepatic stellate cells and
      dimethylnitrosamine-intoxicated rats.
AB  - Tumor necrosis factor-alpha (TNF-alpha) plays a central role in cellular
      necrosis, apoptosis, organ failure, tissue damage, inflammation and fibrosis.
      These processes, occurring in liver injury, may lead to cirrhosis. Thalidomide,
      alpha-N-phthalidoglutarimide, (C(13)H(10)N(2))(4), has been shown to have
      immunomodulatory and anti-inflammatory properties, possibly mediated through its
      anti-TNF-alpha effect. In this study, we investigated the in vitro and in vivo
      effects of thalidomide on hepatic fibrosis. A cell line of rat hepatic stellate
      cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1)
      or TNF-alpha. The inhibitory effects of thalidomide on the NFkappaB signaling
      cascade and fibrosis markers including alpha-smooth muscle actin (alpha-SMA) and
      collagen, were assessed. An in vivo therapeutic study was conducted in
      dimethylnitrosamine (DMN)-treated rats, which were randomly assigned to 1 of 4
      groups: vehicle (0.7% carboxyl methyl cellulose, CMC), thalidomide (40 mg/kg),
      thalidomide (200 mg/kg), or silymarin (50 mg/kg), each given by gavage twice
      daily for 3 weeks starting after 1 week of DMN administration. Thalidomide (100
      800 nM) concentration-dependently inhibited NFkappaB transcriptional activity
      induced by TNF-alpha, including IKKalpha expression and IkappaBalpha
      phosphorylation in HSC-T6 cells. In addition, thalidomide also suppressed TGF
      beta1-induced alpha-SMA expression and collagen deposition in HSC-T6 cells.
      Fibrosis scores of livers from DMN-treated rats receiving high dose of
      thalidomide (0.89 +/- 0.20) were significantly reduced in comparison with those
      of DMN-treated rats receiving vehicle (1.56 +/- 0.18). Hepatic collagen contents
      of DMN rats were also significantly reduced by either thalidomide or silymarin
      treatment. Immunohistochemical double staining results showed that alpha-SMA- and
      NFkappaB-positive cells were decreased in the livers from DMN rats receiving
      either thalidomide or silymarin treatment. In addition, real-time PCR analysis
      indicated that hepatic mRNA expressions of TGF-beta1, alpha-SMA, collagen
      1alpha2, TNF-alpha and iNOS genes were attenuated by thalidomide treatment. In
      conclusion, our results showed that thalidomide inhibited activation of HSC-T6
      cells by TNF-alpha and ameliorated liver fibrosis in DMN-intoxicated rats.

PMID- 16604422
TI  - Assessment of the effects of increased relaxation dispersion data on the
      extraction of 3-site exchange parameters characterizing the unfolding of an SH3
      domain.
AB  - Recently a suite of six CPMG relaxation dispersion experiments has been described
      for quantifying millisecond time-scale exchange processes in proteins. The
      methodology has been applied to study the folding reaction of a G48M Fyn SH3
      domain mutant that exchanges between the native state, and low populated unfolded
      and intermediate states. A complex non-linear global optimization protocol allows
      extraction of the kinetics and thermodynamics of the 3-site exchange process from
      the experimental data, as well as reconstruction of the amide group chemical
      shifts of the excited states. We show here, through a series of Monte-Carlo
      simulations on various synthetic data sets, that the 3-site exchange parameters
      extracted for this system on the basis of (15)N single-quantum (SQ) dispersion
      profiles exclusively, recorded at a single temperature, are significantly in
      error. While a temperature dependent (15)N study improves the robustness of
      extracted parameters, as does a combined analysis of (15)N and (1)H SQ data sets
      measured at a single temperature, the best agreement is observed in cases where
      the full complement of six dispersion profiles per residue is analyzed.

PMID- 16604423
TI  - Rapid determination of protein solubility and stability conditions for NMR
      studies using incomplete factorial design.
AB  - Sample preparation constitutes a crucial and limiting step in structural studies
      of proteins by NMR. The determination of the solubility and stability (SAS)
      conditions of biomolecules at millimolar concentrations stays today empirical and
      hence time- and material-consuming. Only few studies have been recently done in
      this field and they have highlighted the interest of using crystallogenesis tools
      to optimise sample conditions. In this study, we have adapted a method based on
      incomplete factorial design and making use of crystallisation plates to quantify
      the influence of physico-chemical parameters such as buffer pH and salts on
      protein SAS. A description of the experimental set up and an evaluation of the
      method are given by case studies on two functional domains from the bacterial
      regulatory protein LicT as well as two other proteins. Using this method, we
      could rapidly determine optimised conditions for extracting soluble proteins from
      bacterial cells and for preparing purified protein samples sufficiently
      concentrated and stable for NMR characterisation. The drastic reduction in the
      time and number of experiments required for searching protein SAS conditions
      makes this method particularly well-adapted for a systematic investigation on a
      large range of physico-chemical parameters.

PMID- 16604424
TI  - Comparison of different torsion angle approaches for NMR structure determination.
AB  - A new procedure for NMR structure determination, based on the Internal Coordinate
      Molecular Dynamics (ICMD) approach, is presented. The method finds biopolymer
      conformations that satisfy usual NMR-derived restraints by using high temperature
      dynamics in torsion angle space. A variable target function algorithm gradually
      increases the number of NOE-based restraints applied, with the treatment of
      ambiguous and floating restraints included. This soft procedure allows combining
      artificially high temperature with a general purpose force-field including
      Coulombic and Lennard-Jones non-bonded interactions, which improves the quality
      of the ensemble of conformations obtained in the gas-phase. The new method is
      compared to existing algorithms by using the structures of eight ribosomal
      proteins earlier obtained with state-of-the-art procedures and included into the
      RECOORD database [Nederveen, A., Doreleijers, J., Vranken, W., Miller, Z.,
      Spronk, C., Nabuurs, S., Guntert, P., Livny, M., Markley, M., Nilges, M., Ulrich,
      E., Kaptein, R. and Bonvin, A.M. (2005) Proteins, 59, 662-672]. For the majority
      of tested proteins, the ICMD algorithm shows similar convergence and somewhat
      better quality Z scores for the phi, psi distributions. The new method is more
      computationally demanding although the overall load is reasonable.

PMID- 16604425
TI  - Utilization of methyl proton resonances in cross-saturation measurement for
      determining the interfaces of large protein-protein complexes.
AB  - Cross-saturation experiments allow the identification of the contact residues of
      large protein complexes (MW>50 K) more rigorously than conventional NMR
      approaches which involve chemical shift perturbations and hydrogen-deuterium
      exchange experiments [Takahashi et al. (2000) Nat. Struct. Biol., 7, 220-223]. In
      the amide proton-based cross-saturation experiment, the combined use of high
      deuteration levels for non-exchangeable protons of the ligand protein and a
      solvent with a low concentration of (1)H(2)O greatly enhanced the selectivity of
      the intermolecular cross-saturation phenomenon. Unfortunately, experimental
      limitations caused losses in sensitivity. Furthermore, since main chain amide
      protons are not generally exposed to solvent, the efficiency of the saturation
      transfer directed to the main chain amide protons is not very high. Here we
      propose an alternative cross-saturation experiment which utilizes the methyl
      protons of the side chains of the ligand protein. Owing to the fast internal
      rotation along the methyl axis, we theoretically and experimentally demonstrated
      the enhanced efficiency of this approach. The methyl-utilizing cross-saturation
      experiment has clear advantages in sensitivity and saturation transfer efficiency
      over the amide proton-based approach.

PMID- 16604427
TI  - Solution structure of the FK506-binding domain of human FKBP38.

PMID- 16604426
TI  - PR-CALC: a program for the reconstruction of NMR spectra from projections.
AB  - Projection-reconstruction NMR (PR-NMR) has attracted growing attention as a
      method for collecting multidimensional NMR data rapidly. The PR-NMR procedure
      involves measuring lower-dimensional projections of a higher-dimensional
      spectrum, which are then used for the mathematical reconstruction of the full
      spectrum. We describe here the program PR-CALC, for the reconstruction of NMR
      spectra from projection data. This program implements a number of reconstruction
      algorithms, highly optimized to achieve maximal performance, and manages the
      reconstruction process automatically, producing either full spectra or subsets,
      such as regions or slices, as requested. The ability to obtain subsets allows
      large spectra to be analyzed by reconstructing and examining only those subsets
      containing peaks, offering considerable savings in processing time and storage
      space. PR-CALC is straightforward to use, and integrates directly into the
      conventional pipeline for data processing and analysis. It was written in
      standard C+ + and should run on any platform. The organization is flexible, and
      permits easy extension of capabilities, as well as reuse in new software. PR-CALC
      should facilitate the widespread utilization of PR-NMR in biomedical research.

PMID- 16604428
TI  - Solution structure of the first SRC homology 3 domain of human Nck2.

PMID- 16604429
TI  - Effects of a school-based drug abuse prevention program for adolescents on HIV
      risk behavior in young adulthood.
AB  - Early onset of substance use among adolescents has been found to be associated
      with later risky sexual behaviors. This study examined long-term follow-up data
      from a large randomized school-based drug prevention trial to (1) investigate the
      long-term impact of the prevention program on drug use and sexual behaviors that
      put one at elevated risk for HIV infection; and (2) use growth modeling
      procedures to examine potential mechanisms of intervention effects. Self-report
      survey data were collected from students in the 7th grade, prior to the
      intervention in 1985, and in grades 8, 9, 10, and 12. Participants in the
      intervention condition received a 30-session drug prevention program in 7th
      through 9th grades. Follow-up surveys were completed by 2042 young adults (mean
      age = 24) in 1998. As young adults, participants were considered to be engaging
      in high-risk behavior for HIV infection if they reported having multiple sex
      partners, having intercourse when drunk or very high, and recent high-risk
      substance use. The intervention had a direct protective effect on HIV risk
      behavior in the overall sample in young adulthood. Furthermore, among
      participants receiving 60% or more of the prevention program, analyses showed
      that the intervention significantly reduced growth in alcohol and marijuana
      intoxication over the course of adolescence, which in turn was associated with a
      reduction in later HIV risk behavior. The behavioral effects of competence
      enhancement drug prevention programs can extend to risk behaviors including those
      that put one at risk for HIV infection.

PMID- 16604431
TI  - Singlet oxygen quantum yield determination for a fluorene-based two-photon
      photosensitizer.
AB  - The quantum yield, Phi(Delta), of singlet oxygen generation under two-photon
      excitation has been determined for a fluorene derivative. A photochemical method
      was developed using 1,3-diphenylisobenzofuran (DPBF), a chemical quencher of 1O2,
      and 2-(9,9-didecyl-7-nitrofluoren-2-yl)benzothiazole (1) as a two-photon
      photosensitizer (PS). The photochemical kinetics of the quencher was measured by
      two different fluorescence methods. Fluorene 1 exhibited relatively high singlet
      oxygen quantum yield, Phi(Delta) approximately 0.4 +/- 0.1, and had a two-photon
      absorption cross-section of 28 +/- 5 GM. Thus, 1 may have potential for use as a
      two-photon PS in the near-IR spectral region for biomedical applications.

PMID- 16604435
TI  - Comparative study of neuropsychological correlates in schizophrenia with onset in
      childhood, adolescence and adulthood.
AB  - Childhood onset schizophrenia (COS) patients have marked neuropsychological
      deficits in areas of attention, working memory and executive functions. Similar
      deficits have been found in studies on Adolescent onset (AdOS) and Adult onset
      schizophrenia (AOS). In this study we compared the neuropsychological profile of
      COS with AdOS and AOS to test the hypothesis that earlier the onset greater is
      the severity of illness and greater are the neuropsychological deficits. A sample
      of 15 patients of COS was compared with 20 patients each of AdOS and AOS group.
      Assessment of neuropsychological profile was done using standard
      neuropsychological battery for Indian population. Nahor Benson Test and Bender
      Visual Motor Gestalt Test were used to assess perceptuomotor functioning. COS
      patients showed significantly greater deficits on scales of IQ, memory and
      perceptuomotor skills as compared to AdOS that in turn had greater deficits than
      AOS. The persistence of differences across the three groups inspite of
      controlling for education and age suggest that these deficits may have been
      present even before the onset of illness and was not the result of poor academic
      achievements. These findings also point towards a brain damage in schizophrenia
      that occurs on a continuum of severity with COS being the most virulent, AOS
      being the least and AdOS falling in between these two extremes.

PMID- 16604436
TI  - Home treatment for children and adolescents with psychiatric disorders.
AB  - The study examines the effectiveness of home treatment in 70 children and
      adolescents (aged 6-17 years) with heterogeneous psychiatric disorders. Home
      treatment was offered to parents/children as an alternative to inpatient
      treatment (no randomized group assignment). Interventions were carried out by
      psychiatric nurses (n = 38) and medical students (n = 32) under the supervision
      of experienced child psychiatrists. Assessment of treatment effects was based on
      a structured parent interview and parents', children's and therapists' ratings of
      various aspects of psychosocial functioning. Pre- or post-treatment comparisons
      indicate significant improvement of psychiatric symptoms, severity of the
      disorder, and psychosocial adjustment after three months of home-based
      interventions. Outcome of behavioral interventions carried out by experienced
      nurses was superior, compared to treatment effects achieved by advanced medical
      students. Post-treatment comparison of home-based (n = 70) and inpatient-based (n
      = 35) treatment effects suggests that inpatient treatment all in all was more
      effective. At one-year follow-up, however, the effects of home treatment were
      maintained in a higher number of patients, compared to the stability of effects
      seen after psychiatric hospitalization. Thus, home treatment appears to be an
      effective treatment setting. Motivation and compliance of patient and parents,
      and high skills of the therapists are key ingredients for the success of a home
      based treatment program.

PMID- 16604437
TI  - Suicidal ideation, deliberate self-harm behaviour and suicide attempts among
      adolescent outpatients with depressive mood disorders and comorbid axis I
      disorders.
AB  - OBJECTIVE: We aimed to analyse and compare prevalence and associated clinical
      features of suicidal ideation, self-harm behaviour with no suicidal intent and
      suicide attempts among adolescent outpatients with depressive mood disorders with
      or without comorbidity. METHOD: A sample of 218 consecutive adolescent
      outpatients aged 13-19 years with depressive mood disorders was interviewed using
      K-SADS-PL for DSM-IV Axis I diagnoses. They filled out self-report questionnaires
      assessing depressive and anxiety symptoms. Suicidal behaviour was assessed by K
      SADS-PL suicidality items. RESULTS: Half of the subjects reported suicidal
      ideation or behaviour. There was no difference in prevalence of suicidal
      behaviour between non-comorbid and comorbid mood disorder groups. Multivariate
      logistic regression analyses produced the following associations: (1) suicidal
      ideation with self-reported depressive symptoms and poor psychosocial
      functioning, (2) deliberate self-harm behaviour with younger age and poor
      psychosocial functioning, and (3) suicide attempts with self-reported depressive
      symptoms and poor psychosocial functioning. CONCLUSIONS: Depressed mood
      disorders, whether comorbid or not, are associated with suicidal ideation and
      suicide attempts. Diagnostic assessment should be supplemented by self-report
      methods when assessing suicidal behaviour in depressed adolescents.

PMID- 16604438
TI  - NECA at reperfusion limits infarction and inhibits formation of the mitochondrial
      permeability transition pore by activating p70S6 kinase.
AB  - The A1/A2 adenosine agonist 5'-(N-ethylcarboxamido) adenosine (NECA) limits
      infarction when administered at reperfusion. The present study investigated
      whether p70S6 kinase is involved in this anti-infarct effect. Adult rat
      ventricular myocytes were isolated and incubated in tetramethylrhodamine ethyl
      ester (TMRE, 100 nM), which causes cells to fluoresce in proportion to their
      mitochondrial membrane potential. A reduction in TMRE fluorescence serves as an
      indicator of collapse of the mitochondrial transmembrane potential. Cells were
      subjected to H2O2 (200 microM), which like ischemia induces loss of mitochondrial
      membrane potential. Fluorescence was measured every 3 min and to facilitate
      quantification membrane potential was arbitrarily considered as collapsed when
      fluorescence reached less than 60% of the starting value. Adding NECA (1 mM) to
      the cells prolonged the time to fluorescence loss (48.0+/-3.2 min in the NECA
      group versus 29.5+/-2.2 min in untreated cells, P<0.001) and the mTOR/p70S6
      kinase inhibitor rapamycin (5 nM) abolished this protection (31.3+/-3.4 min).
      Since cyclosporine A offered similar protection, mitochondrial permeability
      transition pore formation is a likely cause of the H2O2-induced loss of
      potential. The direct GSK-3beta inhibitor SB216763 (3 microM) also prolonged the
      time to fluorescence loss (49.2+/-2.1 min, P<0.001 versus control), and its
      protection could not be blocked by rapamycin (42.2+/-2.3 min, P<0.001 versus
      control). NECA treatment (100 nM) of intact isolated rabbit hearts at reperfusion
      after 30 min of regional ischemia decreased infarct size from 33.0+/-3.8% of the
      risk zone in control hearts to 11.8+/-2.0% (P<0.001), and rapamycin blocked this
      NECA-induced protection (38.3+/-3.7%). A comparable protective effect was seen
      for SB216763 (1 microM) with infarct size reduction to 13.5+/-2.3% (P<0.001).
      NECA treatment (200 nM) of intact rabbit hearts at reperfusion also resulted in
      phosphorylation of p70S6 kinase more than that seen in untreated hearts. This
      NECA-induced phosphorylation was blocked by rapamycin. These experiments reveal a
      critical role for p70S6 kinase in the signaling pathway of NECA's
      cardioprotection at reperfusion.

PMID- 16604439
TI  - LAMP-2 deficient mice show depressed cardiac contractile function without
      significant changes in calcium handling.
AB  - OBJECTIVE: Mutations in the highly glycosylated lysosome associated membrane
      protein-2 (LAMP-2) cause, as recently shown, familial Danon disease with mental
      retardation, mild myopathy and fatal cardiomyopathy. Extent and basis of the
      contractile dysfunction is not completely understood. METHODS: In LAMP-2
      deficient mice, we investigated cardiac function in vivo using Doppler
      echocardiography and contractile function in vitro in isolated myocardial
      trabeculae. RESULTS: LAMP-2 deficient mice displayed reduced ejection fraction
      (EF) (58.9+/-3.4 vs. 80.7+/-5.1%, P<0.05) and reduced cardiac output (8.3+/-3.1
      vs. 14.7+/-3.6 ml/min, P<0.05) as compared to wild-type controls. Isolated
      multicellular muscle preparations from LAMP-2 deficient mice confirmed depressed
      force development (3.2+/-0.6 vs. 8.4+/-0.9 mN/mm2, P<0.01). All groups showed
      similar force-frequency behaviour when normalised to baseline force. Post-rest
      potentiation was significantly depressed at intervals>15 s in LAMP-2 deficient
      mice (P<0.05). Although attenuated in absolute force development, the normalised
      inotropic response to increased calcium and beta-adrenoreceptor stimulation was
      unaltered. Electron microscopic analysis revealed autophagic vacuoles in LAMP-2
      deficient cardiomyocytes. Protein analysis showed unaltered levels of SERCA2a,
      calsequestrin and phospholamban. CONCLUSIONS: Cardiac contractile function in
      LAMP-2 deficient mice as a model for Danon disease is significantly attenuated.
      The occurrence of autophagic vacuoles in LAMP-2 deficient myocytes is likely to
      be causal for the depressed contractile function resulting in an attenuated
      cardiac pump reserve.

PMID- 16604440
TI  - Atrial natriuretic peptide administered just prior to reperfusion limits
      infarction in rabbit hearts.
AB  - We investigated whether atrial natriuretic peptide (ANP) given just prior to
      reperfusion reduces infarction in rabbit hearts and whether protection is related
      to activation of protein kinase G (PKG). Isolated rabbit hearts were subjected to
      a 30-min period of regional ischemia; treated hearts received a 20-min infusion
      of ANP (0.1 microM) starting 5 min before 2 h of reperfusion. ANP infusion
      decreased infarction from 31.5+/-2.4% of the risk zone in untreated hearts to
      12.5+/-2.0% (P<0.001). To explore mechanisms of protection ischemic hearts were
      treated simultaneously with ANP and isatin, a blocker of the natriuretic peptide
      receptor, shortly before reperfusion. ANP's protective effect was aborted (36.8+/
      2.9% infarction). There is no acceptable blocker of protein kinase G that can be
      used in intact organs. However, 8-(4-chlorophenylthio)-guanosine 3', 5'-cyclic
      monophosphate (10 microM), a cell-permeable cGMP analog that directly activates
      PKG, was infused from 5 min before to 15 min after reperfusion. The PKG activator
      mimicked ANP's protection with only 18.2+/-3.6% infarction (P<0.001). 5-Hydroxyde
      canoate (5-HD), a putative mitochondrial KATP channel (mKATP) inhibitor,
      abrogated ANP's protection (34.4+/-2.6% infarction). Unexpectedly, 1H
      [1,2,4]oxadiazole- [4,3-a]quinoxalin-1-one (ODQ), a blocker of soluble guanylyl
      cyclase also prevented ANP's infarct-sparing effect. It is unclear whether this
      observation implicated participation of soluble guanylyl cyclase in the mechanism
      or simply a lack of selectivity of ODQ. Finally the reperfusion injury salvage
      kinases (RISK), phosphatidylinositol 3-kinase and extracellular signal-regulated
      kinase, were implicated in ANP's mechanism since either wortmannin or PD98059
      infused at reperfusion prevented ANP's infarct-sparing effect. ANP administered
      just prior to reperfusion protects hearts against infarction, likely by
      activation of PKG, opening of mKATP, and stimulation of downstream kinases.

PMID- 16604441
TI  - Isolation and characterization of SATB2, a novel AT-rich DNA binding protein
      expressed in development- and cell-specific manner in the rat brain.
AB  - AT-rich DNA elements play an important role in regulating cell-specific gene
      expression. One of the AT-rich DNA binding proteins, SATB1 is a novel type of
      transcription factor that regulates gene expression in the hematopoietic lineage
      through chromatin modification. Using DNA-affinity purification followed by mass
      spectrometry we identified and isolated a related protein, SATB2 from the
      developing rat cerebral cortex. SATB2 shows homology to SATB1 and the rat protein
      is practically identical to the mouse and human SATB2. Using competitive EMSA, we
      show that recombinant SATB2 protein binds with high affinity and specificity to
      AT-rich dsDNA. Using RT-PCR, Western analysis and immunohistochemistry we
      demonstrate that SATB2 expression is restricted to a subset of postmitotic,
      differentiating neurons in the rat neocortex at ages E16 and P4. We suggest that
      similar to its homologue SATB1, SATB2 is also involved in regulating gene
      expression through altering chromatin structure in differentiating cortical
      neurons.

PMID- 16604442
TI  - Variations in two gene sequences of Citrus tristeza virus after host passage.
AB  - We estimated genetic variation in two groups of Citrus tristeza virus (CTV)
      isolates: one of them (isolates T385, T317, T318 and T305) derived from a Spanish
      source by successive host passages, and the other (isolates T388 and T390),
      obtained after aphid transmission of a Japanese source. The population structure
      of these isolates had been characterized by single-strand conformation
      polymorphism analysis of genes p18 and p20. The nucleotide sequences of
      representative haplotypes of each isolate and gene were used to estimate genetic
      diversity within and between isolates and to evaluate genetic differentiation
      between populations. Phylogenetic analysis of p18 and p20 sequence variants
      showed two main groups: one them included variants predominant in the severe
      isolates (T318, T305 and T388), and the other comprised variants present in both
      mild (T385, T317) and severe isolates. Most sequence variants of isolate T390
      were not associated to these groups. In some isolates, within-isolate diversity
      was higher than diversity with other isolates because their population contained
      distantly related sequence variants, some of which were genetically close to
      variants predominant in the second isolate. Isolates T388 and T390 were
      genetically different for the two genes, as estimated by the F statistic.
      Furthermore, genetic differentiation between T385 and T317, T318 and T305
      increased after each host passage. Our results suggest that aphid transmission
      and host passage may significantly alter the composition of CTV populations and
      thus be an important factor in their evolution.

PMID- 16604443
TI  - Molecular characterization of HE, M, and E genes of winter dysentery bovine
      coronavirus circulated in Korea during 2002-2003.
AB  - The different bovine coronavirus (BCoV) strains or isolates exhibited various
      degrees of substitutions, resulting in altered antigenicity and pathogenicity of
      the virus. In the previous our study, we demonstrated that the spike glycoprotein
      gene of Korean winter dysentery (WD) BCoV had a genetic property of both enteric
      (EBCV) and respiratory BCoV (RBCV) and were significantly distinct from the
      ancestral enteric strains. In the present study, therefore, we analyzed the other
      structure genes, the hemagglutinin/esterase (HE) protein, the transmembrane (M)
      protein and the small membrane (E) protein to characterize 10 WD BCoV circulated
      in Korea during 2002-2003 and compared the nucleotide and deduced amino acid
      sequences with the other known BCoV. Phylogenetic analysis indicated that the HE
      gene among BCoV could be divided into three groups. The first group included only
      RBCV, while the second group contained calf diarrhea BCoV, RBCV, WD and EBCV,
      respectively. The third group possessed only all Korean WD strains which were
      more homologous to each other and were sharply distinct from the other known
      BCoV, suggesting Korean WD strains had evolutionary distinct pathway. In
      contrast, the relative conservation of the M and E proteins of BCoV including
      Korean WD strains and the other coronaviruses suggested that structural
      constraints on these proteins are rigid, resulting in more limited evolution of
      these proteins. In addition, BCoV and human coronavirus HCV-OC43 contained four
      potential O-glycosylation sites in the M gene. However, the M gene sequence of
      both BCoV and HCV-OC43 might not contain a signal peptide, suggesting the M
      protein might be unlikely to be exposed to the O-glycosylation machinery in vivo.

PMID- 16604444
TI  - Determination of the 5'- and 3'-terminal sequences completes the sequences of the
      two double-stranded RNAs of Penicillium stoloniferum virus S.
AB  - The two genomic segments of Penicillium Stoloniferum virus S (PsV-S), a member of
      the Partitiviridae, were recently sequenced and published. We independantly
      sequenced PsV-S and showed that the original sequence was missing nucleotides at
      both the 5' and 3' termini of both segments. We determined the correct sequence
      in three independent experiments and found the segments to be 1753 bp (encoding
      the RNA-dependant RNA polymerase) and 1581 bp (encoding the Capsid Protein).
      Homology was shown between the 5' and 3' ends of PsV-S and other members of the
      Partitiviridae.

PMID- 16604445
TI  - Molecular characterization of foot-and-mouth disease virus in Hong Kong during
      2001-2002.
AB  - Most of the molecular epidemiological studies of foot-and-mouth disease virus
      (FMDV) are based on comparison of VP1 gene sequence. In this report, The
      nucleotide sequences of the VP1 coding region of FMDV type O strains O/HKN/3/01,
      O/HKN/5/01, O/HKN/12/01, O/HKN/7/02 and O/HKN/10/02, isolated from the disease
      outbreak that occurred in Hong Kong Special Administrative Region (Hong Kong SAR)
      of China during 2001-2002, were determined and compared with the sequences of
      other FMDVs. The results revealed that the VP1 gene of the five isolates had the
      same nucleotide (nt) sequences (639 nt), coding for 213 amino acids, and no
      changes were found either at the critical amino acid sites 144 (Val), 148 (Leu),
      154 (Lys) and 208 (Pro) within the VP1 protein epitope (amino acids 140-160, 200
      213), or in the amino acids 145-147 comprising the arginine-glycine-aspartic acid
      (RGD) sequence that is involved in the adsorption of virus to host cell. Analysis
      of the VP1 gene nucleotide sequence revealed that the five isolates examined were
      most closely related to FMDVs found in Hong Kong from 1991 to 1999 and Taiwan in
      1997. Furthermore, although the critical amino acids on the antigen epitope of
      the prevalent Hong Kong isolates and the serotype O vaccine strain,
      O1/Manisa/Turkey/69, showed relative conservativeness, they were distantly
      related genetically, which showed that there existed variation between the
      prevalent Hong Kong FMDV strains and the vaccine strain.

PMID- 16604446
TI  - A gene similar to the human hyaluronan-mediated motility receptor (RHAMM) gene is
      upregulated during Porcine Circovirus type 2 infection.
AB  - Little is known on the cellular events triggered by the Porcine Circovirus type 2
      (PCV2) in Porcine Multisystemic Wasting Syndrome (PMWS). The differential display
      reverse-transcription PCR (DDRT-PCR) was used to identify cellular target
      molecules in lymph node tissue that were regulated in PMWS. Comparative profile
      analysis of a pool of lymph node tissues from PMWS and healthy animals showed
      that some transcripts were up-regulated in PMWS. Bacterial recombinant clones
      containing up-regulated transcripts were analyzed by reverse dot blot. Clones
      showing enhanced hybridization when probed with cDNAs from PMWS animals were
      sequenced and compared to existing databases. Two of the differentially regulated
      transcripts displayed homology with human genes such as an RNA splicing factor
      and hyaluronan-mediated motility receptor (RHAMM). Clones encoding theses genes
      were subsequently used as probes to analyze their expression pattern in PK15
      cells persistently infected with PCV2. Northern blot analyzes indicated that
      these transcripts were up-regulated in these cells as observed in infected lymph
      node tissue from PMWS cases. A role for the up-regulation of the RHAMM gene is
      proposed.

PMID- 16604447
TI  - Association of two membrane proteins encoded by herpes simplex virus type 2, UL11
      and UL56.
AB  - Herpes simplex virus (HSV) acquires envelope by budding into trans-Golgi network
      (TGN)-derived vesicles. Previous studies showed that the UL11 gene product
      enables efficient virion envelopment and export from infected cells and is
      incorporated into virions as tegument protein. At its N-terminus, UL11 is dually
      acylated by myristoic and palmitoic acids. Fatty acylation of UL11 provides both
      membrane binding strength and Golgi-targeting specificity. We show here that UL11
      interacts with UL56 protein, a tail-anchored type II membrane protein encoded by
      HSV, which associated with the Golgi apparatus and cytoplasmic vesicles. We
      previously showed that UL56 is involved in vesicular transport in infected cells.
      The UL11-UL56 complex localized to the perinuclear region of the cytoplasm in
      infected cells. Fatty acylation of UL11 was important for the formation of the
      UL11-UL56 protein complex. Taken together, our results identify a novel
      interaction between two HSV proteins facilitated by mutual interactions with
      Golgi-derived vesicles.

PMID- 16604448
TI  - Characterization of the sigmaC-encoding gene from musocvy duck reovirus.
AB  - The sigmaC-encoding gene of two muscovy duck reovirus (DRV) S14 and C4 strains
      were cloned and completely sequenced. The open reading frame (ORF) comprised 810
      bp and encoded 269 amino acids with a predicated molecular mass of 29.5 kDa.
      Expressed sigmaC fusion protein in Escherichia coli BL21 strain could be detected
      by Western blotting under duck anti-reovirus polyclonal serum. There are two
      large gap insertions at the N-terminal part of the DRV sigmaC when necessary to
      optimize the alignment of the amino acid sequences of the DRV sigmaC had a
      heptapeptide repeat and leucine zipper patterns structurally related to ARV
      sigmaC. All DRVs grouped into one specified genogroup within Orthoreoviruses
      genus subgroup II. The degree of differences between the S14/C4 and ARV was only
      23-24%, and 21-22%, respectively, at both the nucleotide and deduced amino acid
      levels, suggested that DRVs are quite different from ARVs and should give a
      precise classification for DRVs in Orthoreovirus genus.

PMID- 16604449
TI  - Molecular analysis of Korean isolate of barley yellow mosaic virus.
AB  - The complete sequences of both RNAs of an isolate of barley yellow mosaic virus
      (BaYMV) from Haenam, Korea, were determined. RNA1 is 7639 nucleotides long
      [excluding the 3'-poly(A)], and codes for a 270 kDa polyprotein of 2411 amino
      acids which contains the capsid protein (CP) at the C terminus and seven putative
      non-structural proteins. RNA2 is 3582 nucleotides long and codes for a
      polyprotein of 890 amino acids, which contains a 28 kDa putative proteinase (P1)
      and a 73 kDa polypeptide (P2). The whole sequences of Korean isolate (BaYMV-K)
      closely resembled those of an isolate from Japan (BaYMV-J) (99.6 identical
      nucleotides for RNA1; 99.4 for RNA2) and china (BaYMV-C) (96.7 and 96.2%,
      respectively) than from Germany (BaYMV-G) (93.6 and 90.4%, respectively). The
      greatest differences between the BaYMV-K and BaYMV-J isolates were in the 3'-NCRs
      of RNA1 and 5' NCRs of RNA2 and there were also some other regions of difference
      in Nib Pro (RNA1) and P1 (RNA2). Further, the phylogenetic analysis of CP region
      showed that Asian and European isolates formed distinct clusters. However,
      molecular variations between isolates could not be linked to earlier results
      showing differences in cultivar response.

PMID- 16604451
TI  - Phylogenetic analysis of Turkey astroviruses reveals evidence of recombination.
AB  - Sequence data was obtained from the capsid (ORF-2) and the polymerase (ORF-lb)
      genes of 23 turkey astrovirus (TAstV) isolates collected from commercial turkey
      flocks around the United States between 2003 and 2004. A high level of genetic
      variation was observed among the isolates, particularly in the capsid gene, where
      nucleotide sequence identity among them was as low as 69%. Isolates collected on
      the same farm, on the same day, but from different houses could have as little as
      72% identity between their capsid gene sequences when compared. Phylogenetic
      analysis of the capsid gene revealed no clear assortment by geographic region or
      isolation date. The polymerase gene was more conserved with between 86 and 99%
      nucleotide identity and did assort in a geographic manner. Based on differing
      topologies of the capsid and polymerase gene phylogenetic trees, TAstV appears to
      undergo recombination.

PMID- 16604450
TI  - Searching for a new putative cryptic virus in Pinus sylvestris L.
AB  - Double-stranded RNAs (dsRNAs) were detected in different pine populations in
      Germany and Hungary. Two dsRNA species of 1.5 and 1.58 kbp, respectively,
      persisted in the same trees for at least 2 years and their presence was not
      associated with any symptoms. The dsRNAs were found to sediment in the VLP (virus
      like particles) fraction and to be protected by protein(s) against RNase A
      digestion at low salt. cDNA cloning and sequencing of the smaller segment
      (dsRNA2) led to the identification of a putative RNA-dependent RNA-polymerase
      (RdRp) containing the GDD, as well as three other, conserved motifs. Sequence
      comparison with different RNA viruses and phylogenetic analysis indicates that
      the putative RdRp from pine shows highest similarity to the homologous proteins
      of Beet cryptic virus 3 and of a cryptic virus of Pyrus pyrifolia. On the basis
      of these results we suggest that the 1.5 and 1.58 kbp dsRNAs in P. sylvestris may
      represent the genomic segments of a new plant cryptic virus, Cryptoviruses have
      not yet been reported to occur in Gymnosperms.

PMID- 16604452
TI  - The role of pp38 in regulation of Marek's disease virus bi-directional promoter
      between pp38 and 1.8-kb mRNA.
AB  - Marek's disease virus (MDV) contains a bi-directional promoters located between
      pp38 gene and 1.8-kb mRNA in the long inverted repeat region of the viral genome.
      The involvement of pp38 gene in up-regulating the activity of these promoters was
      analyzed by transient expression of chloramphenicol acetyltransferase (CAT)
      reporter gene. Two CAT reporter plasmids, pP(pp38)-CAT and pP(1.8-kb)-CAT, were
      constructed to express CAT under the control of the bi-directional promoter in
      both orientations. These plasmids were transfected into chicken embryonic
      fibroblast (CEF), infected with rMd5 and pp38 deleted rMd5 (rMd5/Deltapp38),
      respectively. No CAT activity was detected in uninfected CEF as expected. CAT
      activities in rMd5/Deltapp38 virus infected CEF (rMd5/Deltapp38-CEF) were 3.5
      fold lower using pP(pp38)-CAT and 12-fold lower using pP(1.8-kb)-CAT than those
      of the parental rMd5 infected CEF (rMd5-CEF). The significantly lower promoter
      activity in the pp38 deletion virus suggests that pp38 can regulate the activity
      of the bi-directional promoters, especially in the direction of 1.8-kb mRNA
      family. Co-transfection of pp38-expressing plasmid (pcDNA-pp38) into
      rMd5/Deltapp38-CEF significantly increased the activity of the bi-directional
      promoters using either pP(pp38)-CAT or pP(1.8-kb)-CAT. DNA mobility shift assay
      showed a binding of the 73-bp sequence of the bi-directional promoter with rMd5
      CEF but not with rMd5/Deltapp38-CEF or uninfected CEF lysates. However,
      rMd5/Deltapp38-CEF lysates could bind the same 73-bp promoter sequence when co
      transfected with pp38-expressing plasmid (pcDNA-pp38). All these data taken
      together suggest pp38 plays an important role in regulating the transcriptional
      activity of the bi-directional promoter.

PMID- 16604453
TI  - Genomic analysis of recombinant sabin clinical isolates.
AB  - Recombination in Poliovirus vaccine strains is a very frequent phenomenon. In
      this report 23 polio/Sabin strains isolated from healthy vaccinees or from VAPP
      patients after OPV administration, were investigated in order to identify
      recombination sites from 2C to 3D regions of the poliovirus genome. RT-PCR,
      followed by Restriction Fragment Length Polymorphism (RFLP) screening analysis
      were applied in four distant genomic regions (5' UTR, VP1, 2C and 3C-3D) in order
      to detect any putative recombinant. The detected recombinants were sequenced from
      2C to the end of the genome (3' UTR) and the exact recombination sites were
      determined with computational analysis. Five of the 23 isolated strains were
      recombinant in one genomic region, two of them in 2C, isolates EP16:S3/S2,
      EP23:S3/S1, two in 3D isolates EP6:S2/S1, EP12:S2/S1 and one in 3A isolate
      EP9:S2/Sl. Point mutations were found in strains EP3, EP6, EP9 and EP12.
      Recombination specific types and sites re-occurrence along with point mutations
      are discussed concerning the polioviruses evolution.

PMID- 16604454
TI  - Herpesvirus papio 2 (HVP2): sequence analysis of the unique short (US) region.

PMID- 16604455
TI  - Metabolic engineering of plants to produce very long-chain polyunsaturated fatty
      acids.
AB  - Very long-chain polyunsaturated fatty acids (VLCPUFAs) are essential for human
      health and well-being. However, the current sources of these valuable compounds
      are limited and may not be sustainable in the long term. Recently, considerable
      progress has been made in identifying genes involved in the biosynthesis of
      VLCPUFAs. The co-expression of these genes in model systems such as plant embryos
      or yeast provided many valuable insights into the mechanisms of VLCPUFA
      synthesis. The recent successful reconstitution of pathways leading to the
      synthesis of arachidonic acid, eicosapentaenoic acid and finally docosahexaenoic
      acid in oil-seed plants indicates the feasibility of using transgenic crops as
      alternative sources of VLCPUFAs. The various approaches used to attain these
      results and the specific constraints associated with each approach are discussed.

PMID- 16604456
TI  - Number and accuracy of T-DNA insertions in transgenic banana (Musa spp.) plants
      characterized by an improved anchored PCR technique.
AB  - Nineteen transgenic banana plants, produced via Agrobacterium-mediated
      transformation, were analyzed for the integration of T-DNA border regions using
      an improved anchored PCR technique. The method described is a relatively fast,
      three-step procedure (restriction digestion of genomic DNA, ligation of
      'vectorette'-type adaptors, and a single round of suppression PCR) for the
      amplification of specific T-DNA border-containing genomic fragments. Most
      transgenic plants carried a low number of inserts and the method was suitable for
      a detailed characterization of the integration events, including T-DNA border
      integrity as well as the insertion of non-T-DNA vector sequences, which occurred
      in 26% of the plants. Furthermore, the particular band pattern generated by four
      enzyme/primer combinations for each individual plant served as a fingerprint,
      allowing the identification of plants representing identical transformation
      events. Genomic Southern hybridization and nucleotide sequence analysis of
      amplification products confirmed the data obtained by anchored PCR. Sequencing of
      seven right or left border junction regions revealed different T-DNA processing
      events for each plant, indicating a relatively low frequency of precisely nicked
      T-DNA integration among the plants studied.

PMID- 16604457
TI  - Human CD14 expressed in seeds of transgenic tobacco displays similar proteolytic
      resistance and bioactivity with its mammalian-produced counterpart.
AB  - Human CD14 plays an important role in innate immunity by being the key receptor
      of lipopolysaccharide found on Gram-negative bacteria. The recently discovered
      widespread localization of CD14 in secretions and mucosal surfaces reveals its
      extensive anti-microbial properties and numerous potential medical applications.
      To produce active recombinant human CD14 (rhCD14) for massive distribution,
      transgenic tobacco plants were successfully generated to express rhCD14 in the
      seed endosperm under the control of two versions (1.8 kb and 5.1 kb) of the rice
      glutelin Gt-1 promoter. Plant-made rhCD14 proteins reached a concentration of 16
      microg/g of seeds and showed stability, proteolytic resistance to pepsin
      digestion and ability to induce the release of pro-inflammatory IL-6 and IL-8
      cytokines in presence of LPS. The expression of plant rhCD14 in tobacco seeds
      constitutes a promising low-cost and abundant supply of this immune protein to
      further investigate its roles in, impacts on and potential medical applications
      for the innate immune system.

PMID- 16604459
TI  - Consequences of transferring three sorghum genes for secondary metabolite
      (cyanogenic glucoside) biosynthesis to grapevine hairy roots.
AB  - A multigenic trait (biosynthesis of the secondary metabolite, dhurrin cyanogenic
      glucoside) was engineered de novo in grapevine (Vitis vinifera L.). This follows
      a recent report of transfer of the same trait to Arabidopsis (Arabidopsis
      thaliana) using three genetic sequences from sorghum (Sorghum bicolor): two
      cytochrome P450-encoding cDNAs (CYP79A1 and CYP71E1) and a UDPG
      glucosyltransferase-encoding cDNA (sbHMNGT). Here we describe the two-step
      process involving whole plant transformation followed by hairy root
      transformation, which was used to transfer the same three sorghum sequences to
      grapevine. Transgenic grapevine hairy root lines that accumulated transcript from
      none, one (sbHMNGT), two (CYP79A1 and CYP71E1) or all three transgenes were
      recovered and characterisation of these lines provided information about the
      requirements for dhurrin biosynthesis in grapevine. Only lines that accumulated
      transcripts from all three transgenes had significantly elevated cyanide
      potential (up to the equivalent of about 100 mg HCN kg(-1) fresh weight), and
      levels were highly variable. One dhurrin-positive line was tested and found to
      release cyanide upon maceration and can therefore be considered 'cyanogenic'. In
      in vitro dual co-culture of this cyanogenic hairy root line or an acyanogenic
      line with the specialist root-sucking, gall-forming, aphid-like insect, grapevine
      phylloxera (Daktulosphaira vitifoliae, Fitch), there was no evidence for
      protection of the cyanogenic plant tissue from infestation by the insect.
      Consistently high levels of dhurrin accumulation may be required for this to
      occur. The possibility that endogenous grapevine gene expression is modulated in
      response to engineered dhurrin biosynthesis was investigated using microarray
      analysis of 1225 grapevine ESTs, but differences in patterns of gene expression
      associated with dhurrin-positive and dhurrin-negative phenotypes were not
      identified.

PMID- 16604458
TI  - Antisense expression of a NBS-LRR sequence in sunflower (Helianthus annuus L.)
      and tobacco (Nicotiana tabacum L.): evidence for a dual role in plant development
      and fungal resistance.
AB  - A partial sunflower cDNA clone, PLFOR48, segregating with a resistance marker to
      Plasmopara halstedii, the causal agent of downy mildew, has been cloned from the
      mildew resistant sunflower line, RHA 266. PLFOR48 encodes a putative protein with
      a nucleotide-binding site and a leucine-rich repeat domain, showing significant
      homology with previously cloned resistance genes belonging to the TIR-NBS-LRR
      family. Southern blot analysis of non-transgenic sunflower suggests that PLFOR48
      is part of a multigenic family. The potential role of PLFOR48 sequence in
      sunflower resistance to mildew was studied, by assessing loss of function, using
      expression of the antisense cDNA in RHA 266 sunflower line. Quite unexpectedly,
      transgenic sunflower lines displayed severe developmental abnormalities, and in
      particular, on the main meristems of homozygote T2 progeny, thus hampering any
      further challenge inoculation with Plasmopara halstedii. The presence of
      homologous sequences to PLFOR48 in Nicotiana tabacum var Samsun NN, as
      demonstrated by Southern blotting, drove us to consider tobacco as an additional
      model to investigate the potential role of this sequence in fungal resistance.
      Expression of the same antisense cDNA in transgenic tobacco lines gave rise to
      higher degree of susceptibility to Phytophthora parasitica, as well as to severe
      alterations in seed development. These results suggest that PLFOR48 and
      homologous sequences could be involved in both regulating developmental pathways
      and controlling resistance to fungal pathogens.

PMID- 16604460
TI  - Examination of the biological effects of high anionic peroxidase production in
      tobacco plants grown under field conditions. I. Insect pest damage.
AB  - At least 25 wild type and high peroxidase tobacco Nicotiana tabacum L. plants
      were examined semiweekly over several weeks for pest insect distribution and
      damage in a 2 year field study. Incidence and/or severity of naturally occurring
      caterpillar damage (dingy cutworm (Feltia ducens Walker), black cutworm (Agrotis
      ipsilon (Hufnagel), tobacco hornworm (Manduca sexta L.), and false tobacco
      budworm (= corn earworm Helicoverpa zea (Boddie)) was significantly reduced at
      several sample dates for high peroxidase vs. wild type plants. These results
      parallel those of prior laboratory studies with caterpillars. The number of adult
      whiteflies (Trialeurodes vaporariorum (Westwood) per plant was significantly
      reduced on high peroxidase compared to wild type plants on most sample dates in
      both years. The number of plants with leaves containing >100 aphids (primarily
      Myzus persicae Sulzer) per leaf on high peroxidase plants was significantly lower
      that on wild type plants after an equivalent invasion period in both years. A
      significantly higher proportion of aphids were found dead on leaf five of high
      peroxidase compared to wild type plants at most sample dates in both years. These
      results indicate that high peroxidase plants have resistance to a wide range of
      insects, implicating this enzyme as a broad range resistance mechanism.

PMID- 16604462
TI  - Assessment of real-time PCR based methods for quantification of pollen-mediated
      gene flow from GM to conventional maize in a field study.
AB  - Maize is one of the main crops worldwide and an increasing number of genetically
      modified (GM) maize varieties are cultivated and commercialized in many countries
      in parallel to conventional crops. Given the labeling rules established e.g. in
      the European Union and the necessary coexistence between GM and non-GM crops, it
      is important to determine the extent of pollen dissemination from transgenic
      maize to other cultivars under field conditions. The most widely used methods for
      quantitative detection of GMO are based on real-time PCR, which implies the
      results are expressed in genome percentages (in contrast to seed or grain
      percentages). Our objective was to assess the accuracy of real-time PCR based
      assays to accurately quantify the contents of transgenic grains in non-GM fields
      in comparison with the real cross-fertilization rate as determined by
      phenotypical analysis. We performed this study in a region where both GM and
      conventional maize are normally cultivated and used the predominant transgenic
      maize Mon810 in combination with a conventional maize variety which displays the
      characteristic of white grains (therefore allowing cross-pollination
      quantification as percentage of yellow grains). Our results indicated an
      excellent correlation between real-time PCR results and number of cross
      fertilized grains at Mon810 levels of 0.1-10%. In contrast, Mon810 percentage
      estimated by weight of grains produced less accurate results. Finally, we present
      and discuss the pattern of pollen-mediated gene flow from GM to conventional
      maize in an example case under field conditions.

PMID- 16604461
TI  - Efficient and stable transformation of Lactuca sativa L. cv. Cisco (lettuce)
      plastids.
AB  - Transgenic plastids offer unique advantages in plant biotechnology, including
      high-level foreign protein expression. However, broad application of plastid
      genome engineering in biotechnology has been largely hampered by the lack of
      plastid transformation systems for major crops. Here we describe the development
      of a plastid transformation system for lettuce, Lactuca sativa L. cv. Cisco. The
      transforming DNA carries a spectinomycin-resistance gene (aadA) under the control
      of lettuce chloroplast regulatory expression elements, flanked by two adjacent
      lettuce plastid genome sequences allowing its targeted insertion between the rbcL
      and accD genes. On average, we obtained 1 transplastomic lettuce plant per
      bombardment. We show that lettuce leaf chloroplasts can express transgene-encoded
      GFP to approximately 36% of the total soluble protein. All transplastomic T0
      plants were fertile and the T1 progeny uniformly showed stability of the
      transgene in the chloroplast genome. This system will open up new possibilities
      for the efficient production of edible vaccines, pharmaceuticals, and antibodies
      in plants.

PMID- 16604463
TI  - Production of transgenic-clone pigs by the combination of ICSI-mediated gene
      transfer with somatic cell nuclear transfer.
AB  - The objective of this study was to examine whether the ICSI-mediated gene
      transfer method using in vitro matured oocytes and frozen sperm head could
      actually produce transgenic pigs. We also aimed at examining whether transgenic
      pigs can be cloned from somatic cells of a transgenic pig generated by the ICSI
      mediated method. A bicistronic gene constituted of the human albumin (hALB) and
      enhanced green fluorescent protein (EGFP) genes was introduced into pig oocytes
      by the ICSI-mediated method. Transfer of 702 embryos produced by the ICSI
      mediated method into five gilts resulted in 4 pregnancies. When three of the
      recipients, which had received total 312 of the embryos were autopsied, 32
      including 1 transgenic fetuses were obtained. One of the recipients gave birth to
      three live piglets including one transgenic pig, showing a strong green
      fluorescence in the eyeballs, oral mucous membrane and subcutaneous tissues.
      Fluorescent microscopy revealed uniform GFP expression in all cell lines
      established from kidney, lung and muscle of the founder transgenic pig obtained.
      Nuclear transfer of these cells resulted in stable in vitro development of cloned
      embryos into the blastocyst stage, ranging from 12.9 to 19.8%. When 767 of the
      nuclear transfer embryos were transferred to 5 recipients, all became pregnant
      and gave birth to a total of six live transgenic-clones. The transgene copy
      number and integrity in the founder pig were maintained in the primary culture
      cells established from the founder as well as in the clones produced from these
      cells. Our study demonstrates that the ICSI-mediated gene transfer is an
      efficient and practical method to produce transgenic pigs, using frozen sperm
      heads and in vitro matured oocytes. It was also shown that combination of ICSI
      mediated transgenesis and nuclear transfer is a feasible technology of great
      potential in transgenic pig production.

PMID- 16604464
TI  - Urokinase-type plasminogen activator mRNA is expressed in normal developing teeth
      and leads to abnormal incisor enamel in alpha MUPA transgenic mice.
AB  - The urokinase-type plasminogen activator (uPA) is a secreted, inducible serine
      protease implicated in extracellular proteolysis and tissue remodeling. Here we
      detected uPA mRNA through in situ hybridization in developing molar and incisor
      teeth of normal mice at multiple sites of the cap and bell developmental stages.
      The mRNA was confined to epithelial cells, however, was undetectable in
      ameloblasts or their progenitor preameloblasts and the inner enamel epithelium.
      Furthermore, mice of five lines of previously described alphaMUPA transgenic
      mice, carrying a transgene consisting of the uPA cDNA linked downstream from the
      alphaA-crystallin promoter, overexpressed uPA mRNA in the same epithelial sites.
      In addition, alphaMUPA mice showed remarkably high levels of uPA mRNA in
      ameloblasts, however, exclusively in two specific sites late in incisor
      development. First, at the late secretory stage, but only on sides of the
      ameloblast layer. Second, in a limited zone of ameloblasts near the incisal end,
      coinciding with a striking morphological change of the ameloblast layer and the
      enamel matrix. In adult alphaMUPA mice, the incisor teeth displayed discoloration
      and tip fragility, and reduction of the outer enamel as determined by scanning
      electron microscopy. These results suggest that balanced uPA activity could play
      a role in normal tooth development. The alphaMUPA tooth phenotype demonstrates a
      remarkable sensitivity to excessive extracellular proteolysis at the incisor
      maturation stage of amelogenesis.

PMID- 16604465
TI  - Unexpected rescue of alpha-synuclein and multimerin1 deletion in C57BL/6JOlaHsd
      mice by beta-adducin knockout.
AB  - Uniform genetic background of inbred mouse strains is essential in experiments
      with genetically modified mice. In order to assess Add2 (beta-adducin) function,
      its null mutation was produced in embryonic stem cells derived from 129Sv mouse
      and the subsequently obtained mouse mutants were backcrossed for 6 generations
      with C57BL/6JOlaHsd strain. Comparison of brain proteins between mutated and
      control animals by two-dimensional gels linked to mass spectroscopy analysis
      showed expression of Snca (alpha-synuclein) in the mutated animals, but
      unexpectedly not in the control C57BL/6JOlaHsd mice. Comparison between
      C57BL/6JOlaHsd and C57BL/6NCrl mice confirmed the presence of a deletion
      encompassing Snca and in addition Mmrn1 (multimerin1) loci in C57BL/6JOlaHsd
      strain. The segregation of mutated Add2 together with an adjacent part of the
      chromosome 6 derived from 129Sv mice, rescued the loss of these two genes in
      knockout mice on C57BL/6JOlaHsd background. The fact that Add2 knockout was
      compared with the C57BL/6JOlaHsd mouse strain, which is actually a double
      knockout of Snca and Mmrn1 emphasizes a need for information provided by
      commercial suppliers and of exact denominations of substrains used in research.

PMID- 16604466
TI  - Accurate determination of zygosity in transgenic rice by real-time PCR does not
      require standard curves or efficiency correction.
AB  - A number of quantitative, real-time PCR methods have been developed for
      determining transgene copy numbers in plants. Here, we demonstrate that the Roche
      LightCycler system can be used to determine the zygosity of transgenic lines
      without the use of standard curves or efficiency correction calculations. We have
      developed a duplex PCR assay which permits the determination of zygosity,
      relative to a calibrator sample, in transgenic rice lines containing the gene for
      a viral glycoprotein. Our data demonstrate that unambiguous 2-fold discrimination
      of copy number can be attained by calculating relative copy number using the
      threshold crossing point (Ct) calculated by the LightCycler software combined
      with delta delta Ct calculations, provided that the appropriate calibrator sample
      is included in each run. The method presented here is rapid, sensitive, robust
      and easy to optimise.

PMID- 16604468
TI  - BKCa channels activating at resting potential without calcium in LNCaP prostate
      cancer cells.
AB  - Large-conductance Ca2+-dependent K+ (BK(Ca)) channels are activated by
      intracellular Ca2+ and membrane depolarization in an allosteric manner. We
      investigated the pharmacological and biophysical characteristics of a BK(Ca)-type
      K+ channel in androgen-dependent LNCaP (lymph node carcinoma of the prostate)
      cells with novel functional properties, here termed BK(L). K+ selectivity, high
      conductance, activation by Mg2+ or NS1619, and inhibition by paxilline and
      penitrem A largely resembled the properties of recombinant BK(Ca) channels.
      However, unlike conventional BK(Ca) channels, BK(L) channels activated in the
      absence of free cytosolic Ca2+ at physiological membrane potentials; the half
      maximal activation voltage was shifted by about -100 mV compared with BK(Ca)
      channels. Half-maximal Ca2+-dependent activation was observed at 0.4 microM: for
      BK(L) (at -20 mV) and at 4.1 microM: for BK(Ca) channels (at +50 mV).
      Heterologous expression of hSlo1 in LNCaP cells increased the BK(L) conductance.
      Expression of hSlo-beta1 in LNCaP cells shifted voltage-dependent activation to
      values between that of BK(L) and BK(Ca) channels and reduced the slope of the P
      (open) (open probability)-voltage curve. We propose that LNCaP cells harbor a so
      far unknown type of BK(Ca) subunit, which is responsible for the BK(L) phenotype
      in a dominant manner. BK(L)-like channels are also expressed in the human breast
      cancer cell line T47D. In addition, functional expression of BK(L) in LNCaP cells
      is regulated by serum-derived factors, however not by androgens.

PMID- 16604469
TI  - Structure of fully hydrated fluid phase lipid bilayers with monounsaturated
      chains.
AB  - Quantitative structures are obtained at 30 degrees C for the fully hydrated fluid
      phases of palmitoyloleoylphosphatidylcholine (POPC), with a double bond on the sn
      2 hydrocarbon chain, and for dierucoylphosphatidylcholine (di22:1PC), with a
      double bond on each hydrocarbon chain. The form factors F(qz) for both lipids are
      obtained using a combination of three methods. (1) Volumetric measurements
      provide F(0). (2) X-ray scattering from extruded unilamellar vesicles provides
      /F(qz)/ for low q(z). (3) Diffuse X-ray scattering from oriented stacks of
      bilayers provides /F(qz)/ for high q(z). Also, data using method (2) are added to
      our recent data for dioleoylphosphatidylcholine (DOPC) using methods (1) and (3);
      the new DOPC data agree very well with the recent data and with (4) our older
      data obtained using a liquid crystallographic X-ray method. We used hybrid
      electron density models to obtain structural results from these form factors. The
      result for area per lipid (A) for DOPC 72.4 +/- 0.5 A(2) agrees well with our
      earlier publications, and we find A = 69.3 +/- 0.5 A2 for di22:1PC and A = 68.3
      +/- 1.5 A2 for POPC. We obtain the values for five different average thicknesses:
      hydrophobic, steric, head-head, phosphate-phosphate and Luzzati. Comparison of
      the results for these three lipids and for our recent
      dimyristoylphosphatidylcholine (DMPC) determination provides quantitative
      measures of the effect of unsaturation on bilayer structure. Our results suggest
      that lipids with one monounsaturated chain have quantitative bilayer structures
      closer to lipids with two monounsaturated chains than to lipids with two
      completely saturated chains.

PMID- 16604470
TI  - The glycine residues G551 and G1349 within the ATP-binding cassette signature
      motifs play critical roles in the activation and inhibition of cystic fibrosis
      transmembrane conductance regulator channels by phloxine B.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) protein contains a
      canonical ATP-binding cassette (ABC) signature motif, LSGGQ, in nucleotide
      binding domain 1 (NBD1) and a degenerate LSHGH in NBD2. Here, we studied the
      contribution of the conserved residues G551 and G1349 to the pharmacological
      modulation of CFTR chloride channels by phloxine B using iodide efflux and whole
      cell patch clamp experiments performed on the following green fluorescent protein
      (GFP)-tagged CFTR: wild-type, delF508, G551D, G1349D, and G551D/G1349D double
      mutant. We found that phloxine B stimulates and inhibits channel activity of wild
      type CFTR (Ks = 3.2 +/- 1.6 microM: , Ki = 38 +/- 1.4 microM: ) and delF508 CFTR
      (Ks = 3 +/- 1.8 microM: , Ki = 33 +/- 1 microM: ). However, CFTR channels with
      the LSGDQ mutated motif (mutation G551D) are activated (Ks = 2 +/- 1.13 microM: )
      but not inhibited by phloxine B. Conversely, CFTR channels with the LSHDH mutated
      motif (mutation G1349D) are inhibited (Ki = 40 +/- 1.01 microM: ) but not
      activated by phloxine B. Finally, the double mutant G551D/G1349D CFTR failed to
      respond not only to phloxine B stimulation but also to phloxine B inhibition,
      confirming the importance of both amino acid locations. Similar results were
      obtained with genistein, and kinetic parameters were determined to compare the
      pharmacological effects of both agents. These data show that G551 and G1349
      control the inhibition and activation of CFTR by these agents, suggesting
      functional nonequivalence of the signature motifs of NBD in the ABC transporter
      CFTR.

PMID- 16604472
TI  - A surgical indication in incurable breast cancer.

PMID- 16604471
TI  - The activation pathway of the volume-sensitive organic osmolyte channel in
      Xenopus laevis oocytes expressing skate anion exchanger 1 (AE1).
AB  - When swollen, skate red blood cells increase permeability and allow efflux of a
      number of solutes, including taurine. Hypoosmosis-induced taurine permeability
      appears to involve the red cell anion exchanger. However, three isoforms have
      been cloned from these cells. Therefore, to determine the ability of the
      individual isoform skate anion exchanger 1 (skAE1) to mediate hypoosmosis-induced
      taurine permeability as well as associated regulatory events, skAE1 was expressed
      in Xenopus oocytes. This study focused on investigating the role of tyrosine
      kinases and lipid rafts in the regulation of the channel. The results showed that
      tyrosine kinase inhibitors and lipid raft-disrupting agents inhibited the volume
      sensitive organic osmolyte channel while protein tyrosine phosphatase inhibitors
      activated the channel in oocytes expressing skAE1. To study the role of lipid
      rafts in the activation of the volume-sensitive organic osmolyte channel, the
      cellular localization of skAE1 was investigated. Also, the role of tyrosine
      kinases was investigated by examining the tyrosine phosphorylation state of
      skAE1. Hypoosmotic stress induced mobilization of skAE1 into light membranes and
      the cell surface as well as tyrosine phosphorylation of skAE1. These events are
      involved in the activation of the volume-sensitive organic osmolyte channel in
      Xenopus oocytes expressing skAE1.

PMID- 16604473
TI  - Colorectal cancer screening and surveillance: current standards and future
      trends.
AB  - Its prevalence, long premalignant course, and favorable response to early
      intervention make colorectal cancer an ideal target for screening regimens. The
      success of these regimens depends on accurate assessment of risk factors, patient
      compliance with scheduled visits and tests, and physician knowledge of screening
      strategies. We review the current recommendations for colorectal cancer screening
      in general and at-risk populations, comment on surveillance methods in high-risk
      patients, and examine current trends that will likely influence screening
      regimens in the future.

PMID- 16604474
TI  - Clinicopathologic characteristics and surgical outcomes of mucinous gastric
      carcinoma.
AB  - BACKGROUND: The clinicopathologic characteristics of mucinous gastric carcinoma
      (MGC), an uncommon subtype of gastric carcinoma, were examined by comparing 45
      MGC and 1255 non-MGC (NGC) cases. METHODS: Of 1300 gastric cancer patients, 1184
      (early, n=568; advanced, n=616) underwent potentially curative or palliative
      resection. Age, sex, tumor location, tumor diameter, macroscopic appearance,
      depth of invasion, lymph node metastasis, lymphatic invasion, and venous invasion
      were monitored. RESULTS: In all registered patients, MGC patients'
      characteristics were as follows: advanced-stage disease (P=.0293),
      macroscopically ill-defined tumors (P=.0051), deeper invasion (P=.0046), and more
      lymph node involvement (P=.0008). Although there were no significant differences
      between curatively resected MGC and NGC advanced-cancer patients, in curatively
      resected early-cancer patients, depth of invasion (P=.0060) and lymphatic
      invasion (P=.0374) were significantly different. Survival time in all registered
      patients was shorter for MGC patients (P=.0489). Survival of curatively resected
      advanced and early gastric cancer patients was not significantly different. Age,
      macroscopic appearance, tumor diameter, depth of invasion, lymph node metastasis,
      and curability, but not histological type, were independent prognostic factors in
      all registered patients. Histological type also did not influence prognosis after
      curative resection. MGC patients had significantly more metastatic lymph nodes
      and lymphatic and venous invasion. Survival was significantly different (P=.0450)
      between all patients with undifferentiated and differentiated MGC, but not in
      curatively resected patients. CONCLUSIONS: MGC patients' poor prognosis
      correlates with advanced disease at diagnosis. Therapeutic and follow-up plans
      after curative resected MGC and NGC should remain the same, possibly with
      alterations according to the former's histological subtype.

PMID- 16604475
TI  - Prognostic significance of residual breast disease and axillary node involvement
      for patients who had primary induction chemotherapy for advanced breast cancer.
AB  - BACKGROUND: We performed this study to determine the prognostic significance of
      clinical tumor size, pathologic measurement of residual tumor, and number of
      positive axillary nodes in the surgical specimen relative to overall survival for
      patients who underwent primary induction chemotherapy for advanced breast cancer.
      METHODS: Data, collected prospectively between 1997 and 2002, included clinical
      tumor-node-metastasis stage, age at diagnosis, hormone receptor status, type of
      preoperative chemotherapy, histological type, surgical procedure, pathologic
      measurement in centimeters of residual breast tumor, and the number of positive
      axillary nodes in the surgical specimen. Univariable correlates of residual
      breast disease were assessed by using the chi2 test. Recursive partitioning
      analysis was used to determine the prognostic significance of clinical tumor
      size, residual tumor size, and pathologic node involvement relative to overall
      survival. Survival was estimated by using the method of Kaplan and Meier and
      compared by using the log-rank test. A P value of <.05 was considered
      significant. RESULTS: Data were available for 85 patients with advanced breast
      cancer. Although univariable analysis identified increasing age, clinically
      involved axillary nodes, and a higher clinical tumor-node-metastasis stage as
      predictors of an increased risk of residual disease, recursive partitioning
      analysis identified more than three involved axillary nodes in the surgical
      specimen, with or without any measurable residual breast disease, as the most
      significant predictor of decreased survival (P<.001). CONCLUSIONS: Pathologic
      axillary node involvement was the most significant predictor of decreased
      survival for patients who had undergone primary induction chemotherapy for
      advanced breast cancer.

PMID- 16604476
TI  - Melanoma patients with positive sentinel nodes who did not undergo completion
      lymphadenectomy: a multi-institutional study.
AB  - BACKGROUND: Completion lymph node dissection (CLND) is considered the standard of
      care in melanoma patients found to have sentinel lymph node (SLN) metastasis.
      However, the therapeutic utility of CLND is not known. The natural history of
      patients with positive SLNs who do not undergo CLND is undefined. This multi
      institutional study was undertaken to characterize patterns of failure and
      survival rates in these patients and to compare results with those of positive
      SLN patients who underwent CLND. METHODS: Surgeons from 16 centers contributed
      data on 134 positive-SLN patients who did not undergo CLND. SLN biopsy was
      performed by using each institution's established protocols. Patients were
      followed up for recurrence and survival. RESULTS: In this study population, the
      median age was 59 years, and 62% were male. The median tumor thickness was 2.6
      mm, 77% of tumors had invasion to Clark level IV/V, and 33% of lesions were
      ulcerated. The primary melanoma was located on the extremities, trunk, and
      head/neck in 45%, 43%, and 12%, respectively. The median follow-up was 20 months.
      The median time to recurrence was 11 months. Nodal recurrence was a component of
      the first site of recurrence in 20 patients (15%). Nodal recurrence-free survival
      was statistically insignificantly worse than that seen in a contemporary cohort
      of patients who underwent CLND. Disease-specific survival for positive-SLN
      patients who did not undergo CLND was 80% at 36 months, which was not
      significantly different from that of patients who underwent CLND. CONCLUSIONS:
      This study underscores the importance of ongoing prospective randomized trials in
      determining the therapeutic value of CLND after positive SLN biopsy in melanoma
      patients.

PMID- 16604477
TI  - Biased distribution of single nucleotide polymorphisms (SNPs) in porcine Toll
      like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes.
AB  - Toll-like receptors (TLRs) recognize various microbial components and induce
      immune responses. Polymorphisms in TLRs may influence their recognition of
      pathogen-derived molecules; swine TLRs are predicted to be associated with
      responses to infectious diseases such as pneumonia. In this study, we searched
      for single nucleotide polymorphisms (SNPs) in the coding sequences of porcine
      TLR1, TLR2, TLR4, TLR5, and TLR6 genes in 96 pigs from 11 breeds and elucidated
      21, 11, 7, 13, and 11 SNPs, respectively, which caused amino acid substitutions
      in the respective TLRs. Distribution of these nonsynonymous SNPs was biased; many
      were located in the leucine-rich repeats, particularly in TLR1. These data
      demonstrated that the heterogeneity of TLR genes was preserved in various porcine
      breeds despite intensive breeding that was carried out for livestock improvement.
      It suggests that the heterogeneity in TLR genes is advantageous in increasing the
      possibility of survival in porcine populations.

PMID- 16604478
TI  - Study on the genetic mutations of 17 alpha-hydroxylase/17,20-lyase deficiency in
      Chinese patients.
AB  - OBJECTIVE: To investigate the CYP17A1 gene mutations in Chinese patients with 17
      alpha-hydroxylase/17, 20-lyase deficiency. METHODS: Clinical data were
      retrospectively analyzed. The CYP17A1 gene mutations were detected in 5 cases
      with 17 alpha-hydroxylase/17, 20-lyase deficiency and their relatives. The
      genomic DNA of the patients was isolated from whole blood. Seven pairs of primers
      were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene.
      The amplified PCR products were purified by agarose gel and then directly
      sequenced. In order to confirm the DNA sequences of different alleles, some
      fragments were inserted into pMD 18-T vector and then sequenced. Sequencing
      results were compared to the established human CYP17A1 sequence. RESULTS:
      Briefly, we found 2 kinds of compound mutations, of which were: (1) 6436-6438(TAC
      ->AA), causing amino acid Y329K, 418X; (2) 6531-6532(GC-->A), causing amino acid
      L361F, 418X. Among the five cases, four were homozygous for 6436-6438(TAC-->AA),
      whereas one was compound heterozygous for 6436-6438(TAC-->AA)/6531-6532(GC-->A).
      The clinical characteristics of 5 cases were all completely combined defects of
      17 alpha-hydroxylase/17, 20-lyase, and they all carried two alleles of CYP17A1
      gene mutations that all shifted the reading frame and resulted in truncated
      protein which lack of the activity center site of P450C17, of which corresponding
      with their clinical feature. CONCLUSION: Nine alleles have the mutation of 6436
      6438(TAC-->AA), accounting for 90% of total alleles (9/10). That suggests this
      kind of mutation may have racial specificity. More study should be done to have
      better understanding of the function of the truncated P450C17 enzymes.

PMID- 16604479
TI  - Association of bone metabolism related genes polymorphisms with the effect of
      raloxifene hydrochloride on bone mineral density and bone turnover markers in
      postmenopausal women with osteoporosis.
AB  - OBJECTIVE: To investigate the association of bone metabolism related genes
      polymorphisms with the effect of raloxifene hydrochloride(RLX) on bone mineral
      density (BMD) and bone turnover markers in postmenopausal women with
      osteoporosis. METHODS: A total of 68 unrelated postmenopausal women with
      osteoporosis of Han ethnicity aged 47-74 years were randomly divided into 2
      groups of 34 women: RLX group (60 mg were given daily for 12 months) and placebo
      group. BMD and bone turnover markers were measured at baseline, 6 and 12 months
      after treatment. The polymorphisms of Xba I and Pvu II sites in estrogen receptor
      1 gene(ESR1), Ras I site in ESR2 gene, and start codon (Fok I) and CDX2 binding
      sites in vitamin D receptor gene (VDR) were analyzed. RESULTS: A total of 58
      patients completed 12 months of study period. By the end of study, the increased
      percentage of BMD in lumbar spine 2-4 (L2-4), total hip, and trochanter were
      found significantly different between RLX group and placebo group(P<0.05), and
      the decreased percentage of C-telopeptide and osteocalcin were significantly
      different between the two groups (P<0.01). The BMD of total hip and trochanter of
      women with FF genotypes of VDR Fok I site were decreased by 1.98%+/-4.86% and
      2.26%+/-4.73% respectively in the RLX group, but those of women with Ff/ff
      genotypes were increased by 2.52%+/-2.75% and 2.74 %+/-2.97%,
      respectively(P<0.05). Moreover, the total hip BMD of women with PP/Pp genotypes
      of ESR1 Pvu II site was increased by 2.12%+/-2.78%, and of women with pp genotype
      it was decreased by 1.34%+/-3.73%(P<0.05). However, no significant association
      was observed of the polymorphisms of five sites with the changes of BMD and bone
      turnover markers in the placebo group. CONCLUSION: The effect of RLX on BMD in
      postmenopausal women with osteoporosis is regulated by the polymorphisms of Fok I
      of VDR gene and Pvu II of ESR1 gene. The study is valuable to select this drug
      according to genotype of patients in clinical.

PMID- 16604480
TI  - Two novel missense mutations of GATA4 gene in Chinese patients with sporadic
      congenital heart defects.
AB  - OBJECTIVE: To identify mutations in GATA4 gene in Chinese patients with sporadic
      congenital heart defects (CHD). METHODS: Single stranded conformation
      polymorphism (SSCP) analysis was performed to screen for mutations in all six
      exons and exon-intron boundaries of GATA4 in 31 individuals with CHD. Direct DNA
      sequencing was used to identify the specific mutations. RESULTS: Two novel
      missense mutations, V267M in exon 4, V380M in exon 6, and one polymorphism in
      intron 6 of GATA4 were identified. CONCLUSION: The above identified two novel
      GATA4 mutations associated with CHD in Chinese patients. This suggests that the
      transcription factor GATA4 may play an important role in cardiogenesis.

PMID- 16604481
TI  - Cloning and sequencing of junction fragment with exons 45-54 deletion of
      dystrophin gene.
AB  - OBJECTIVE: To study the mechanisms of dystrophin gene deletion, the junction
      fragment with exons 45-54 deletion were cloned and sequenced. METHODS: A Duchenne
      muscular dystrophy (DMD) patient with exons 45-54 deletion has been substantiated
      by PCR amplification of the exons. Then we used a PCR-based genome-walking method
      for localizing the breakpoints in introns 44 and 54. At last, 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 breakpoints in
      introns 45 and 54. The sequencing result of the deletion-junction fragment was
      compared with the normal intronic sequences. RESULTS: A total of 2716 bp sequence
      containing the junction fragment was obtained. The 5' breakpoint was located in
      LINE/L1 element of intron 44 and close to a matrix attachment region (MAR). The
      3' breakpoint was located in the minor potential MAR with topoisomerase II
      cleavage sites around. Beside the 3' breakpoint there was a 6 bp palindromic
      sequence. A 4 bp microhomologous sequence (AGAG) was in the joint of the deletion
      junction fragment. CONCLUSION: The nonhomologous recombination caused by L1
      repeated element, topoisomerase II cleavage sites, MARs and the nonhomologous end
      joining of microhomologous sequence may be the important factors in this huge
      gene fragment deletion.

PMID- 16604482
TI  - Gene expression patterns in gastric cancer.
AB  - OBJECTIVE: To identify gene expression patterns in distinct stages of intestinal
      type gastric cancer(GC). METHODS: Gene expression patterns of distinct stages of
      intestinal-type GC samples from 3 patients were compared with cDNA microarray,
      which contained 576 genes. There were 506 target genes, which included 51 genes
      identified from our previous experiment with suppression subtractive
      hybridization(SSH) and other 455 genes chosen for their important roles in
      cancers. Hierarchical clustering was performed to clarify genes in association
      with distinct stages of GC. RESULTS: One hundred and eighty-one differentially
      expressed genes with average Cy5:Cy3 ratios higher than 2.0 or lower than 0.5 in
      at least one stage of GC were identified by cDNA microarray. Among them, 48 genes
      were up-regulated and 133 down-regulated. Hierarchical clustering analysis
      separated the differentially expressed genes in different stages of GC into 5
      main characteristic groups. Some important differentially expressed genes in
      different stages of GC were identified, such as SEC23IP, LIPF, ES(BQ291520),
      SLC5A1, PG(encoding similar to pepsin A precursor), CXCR4, DICER1, SH3GL2, and
      IGF2R. CONCLUSION: The differentially expressed gene patterns and some important
      genes were identified, which might be useful in further study on carcinogenesis,
      progression and metastasis of intestinal-type GC.

PMID- 16604483
TI  - [A mutation 1633-26(C-->A) in EXT1 gene causes multiple exostoses].
AB  - OBJECTIVE: To study the gene mutation in a patient with multiple exostoses,
      identify the disease-causing gene mutation. METHODS: Polymerase chain reaction
      and DNA sequencing were used to screen the EXT1 or EXT2 gene mutation, while
      mismatch primer amplification and restriction endonuclease digestion were
      performed to confirm the mutation. RESULTS: By DNA sequencing, a mutation in the
      seventh intron was detected and located at 26 bp of 3' splice site upstream in
      EXT1 gene, which was unreported before. Mismatch primer amplification and
      restriction fragment length polymorphism analysis suggested that this mutation
      was not detected in the normal control. CONCLUSION: The mutation 1633-26(C-->A)
      may be the disease-causing mutation in this patient with multiple exostoses.

PMID- 16604484
TI  - [A comparative research on RHD gene structures of Chinese Han and Uigur
      population].
AB  - OBJECTIVE: To research comparatively on the RHD gene structures in unrelated RhD
      negative individuals of Chinese Uigur and Han population. METHODS: The upstream,
      downstream, hybrid box and 10 exons of RHD gene were detected with sequence
      specific primer-PCR technique. RESULTS: The results showed the genotypes of RhD
      negative individuals to have the significant difference between Chinese Uigur and
      Han population, that 94.44% Uigur individuals were with RHD(-)/RHD(-) genotype
      but just 61.40% Han population were with this genotype(94.44% versus 61.40%,
      P<0.01); 2.78% Uigur individuals were with RHD(+)/RHD(-) genotype but 34.21% Han
      population were with this genotype(2.78% versus 34.21%, P<0.01). However, there
      was significantly no RHD(+)/RHD(+) genotype difference between Chinese Uigur and
      Han population(2.78% versus 4.39%, P>0.05). In 78 cases of RhD negative Chinese
      Hans with single RHD gene, of which the RHD gene structure showed that 53(67.95%)
      cases were RHD(1-10) allele(of 53 RHD(1-10) alleles, 14 alleles were
      unexpressed); 15(19.23%) were RHD-CE(2-9)-D(2) allele; 5(6.41%) cases were RHD
      CE(2-7)-D(2) allele; 2(2.56%) were similar to RHD-CE(3-6)D allele; 1(1.28%) case
      was RHD-CE(5-6)-D allele; and 2(2.56%) were RHD-CE(6)-D or point mutation
      respectively. Of 2 RhD negative Chinese Uigurs with RhD(-)/RHD(+) genotype, one
      carried RHD(1-10) allele, another carried RHD-CE(2-9)-D(2) allele. CONCLUSION:
      The most frequently unexpressed RHD alleles were RHD-CE(2-9)-D(2), RHD(1-10) and
      RHD-CE(2-7)-D(2) respectively in Chinese Han population who carried single RHD
      allele with RHD(-) phenotype and RHD(+) genotype. It showed the confluent
      character of RH gene in Chinese Han and Uigur population that there existed
      unexpressed RHD-CE(2-9)-D(2) allele in Chinese Uigur nationality, which was
      infrequent in Chinese Uigur population but frequent in Chinese Han population.

PMID- 16604485
TI  - [HLA-A site genotyping on single blastomeres is studied by nest-PCR-SSP method].
AB  - OBJECTIVE: To assess the accuracy and reliability of the nest-PCR-sequence
      specific primer(SSP) method in HLA-A site genotyping of single blastomeres
      retrieved from human pre-implantation embryos. METHODS: By nest PCR on HLA-A exon
      2, the success rate of first-round amplification was estimated for single
      blastomeres. Based on the first-round amplification, the HLA-A genotype of every
      single blastomeres was analyzed by commercially available PCR-SSP kits. RESULTS:
      The amplification of HLA-A exon 2 were performed to 120 blasotmeres retrieved
      from in vitro fertilization(IVF) surplus embryos donated by 10 couples. The
      average success rate of family 1-5 and 6-10 was 78.2%(43/55) and 93.8%(61/65),
      respectively. And 86.7%(104/120) in total. Eighty blastomeres were further tested
      by nest-PCR-SSP, among which 11 blastomeres failed to HLA-A exon 2 amplification
      and then failed to genotyping while the other 69 blastomeres succeed in HLA-A
      exon 2 amplification and succeed in genotyping. Except for 6 blastomeres that
      were uncertain for allele lost because of parents' homozygosity, the left 63
      blastomeres had accurate HLA genotyping. Among these 63 blastomeres, 59
      blastomeres had genotypes confirmed from their parents(93.6%), 3 blastomeres lost
      one of parents' alleles(4.8%), and only one blastomere had two more than parents'
      alleles(1.6%). CONCLUSION: The above research results indicated that based on the
      successful first round amplification of single blastomeres, nest-PCR-SSP strategy
      offers a convenient and reliable option for HLA genotyping on single blastomeres,
      which is a key process in pre-selecting HLA-identical sibling for allogeneic cord
      blood cell transplantation.

PMID- 16604486
TI  - [Sequencing the Rhesus boxes and determining the homozygosity of RHD gene in Han
      Chinese with RhD negative].
AB  - OBJECTIVE: To analyze the sequences of Rhesus boxes of RhD gene, and explore the
      genetic mechanism of RhD negative phenotype in Chinese Han population. Meanwhile
      the PCR product of Rhesus boxes is analyzed for determining RHD gene
      homozygosity. METHODS: DNA of 74 RhD negative samples were firstly analyzed with
      multiplex PCR-sequence specific primer(SSP). The further analysis was given to
      Rhesus boxes specific sequencing and RHD gene homozygosity determined by PCR
      restriction fragment length polymorphism(RFLP) analysis to Rhesus boxes. RESULTS:
      In DNA samples of 74 RhD negative individuals, 46 samples(62%) showed the absence
      and homozygous negative of RHD gene; 22 samples(30%) all showed the existence of
      RHD specific exons, of which 19 were RHD gene heterozygous and 3 were homozygous;
      regardless of PCR-RFLP analysis showing no RHD specific exons, but further
      analysis of RHD specific PCR revealed one RHD gene, at least RHD gene exon 1 and
      10 existing in 5 DNA samples(7%); 1 sample(1%) was lacking RHD exon 6 although
      the multiplex PCR showed the RHD gene to be positive. Analyzing the hybrid Rhesus
      box of 27 RhD negative samples revealed the Han Chinese population to have the
      same DNA sequence of hybrid Rhesus box as Caucasians. CONCLUSION: The RHD gene
      deletion is the main molecular mechanism of causing RhD negative formed in Han
      Chinese population, who have had the RHD gene deletion taken place within the
      defined breakpoint region as Caucasians.

PMID- 16604487
TI  - [Investigating the correlation between polymorphisms with couple sharing rate of
      TAP gene and hypertensive disorder complicating pregnancy].
AB  - OBJECTIVE: To investigate and clarify whether the genetic susceptibility to women
      with hypertensive disorder complicating pregnancy or pre-eclampsia is associated
      with polymorphisms and couple sharing rate of transporter associate with antigen
      processing genes(TAP). METHODS: One hundred and two severe pre-eclampsia women
      and their spouses served as study group, and 200 normal pregnant women and their
      spouses were selected as control group. All pregnant women were primipara with
      single fetus. Genomic DNA was extracted from 2 mL cubital venous blood. We used
      the amplification refractory mutation system polymerase chain reaction(ARMS-PCR)
      to characterize TAP gene locus 333, 637, 379, 565, 665. RESULTS: We observed
      eleven TAP haplotypes. There were four kinds of haplotypes(1A-1D) existing in
      TAP1, and seven kinds of haplotypes(2A-2G) existing in TAP2. The gene frequencies
      of TAP2B(Chi2=9.19, P<0.01, RR=4.18) and TAP2F(Chi2=5.34, P<0.05, RR=4.63) of
      patient group with pre-eclampsia were significantly higher as compared with
      control group. The analyses of some TAP haplotypes such as TAP1B(Chi2=4.87,
      P<0.05, RR=3.14), TAP1C(Chi2=5.42, P<0.05, RR=4.90), TAP2B(Chi2=9.65, P<0.01,
      RR=5.39) showed that the couple sharing rate of pre-eclampsia women and their
      spouses had statistically a highly significant increase in comparison with that
      of controls. CONCLUSION: Our data suggest that the presence of TAP2B or TAP2F
      haplotypes should be considered as a risk increased to pregnant women being
      susceptible to hypertensive disorder complicating pregnancy; and also the
      elevated couple sharing rates of TAP1B, TAP1C and TAP2B genes will increase the
      opportunity or possibility of pregnant women suffering from pre-eclampsia
      disease.

PMID- 16604488
TI  - [The research on the correlation between eotaxin-3 gene polymorphisms and
      allergic asthma].
AB  - OBJECTIVE: To study in the linkage between eotaxin-3 gene polymorphisms and
      allergic asthma susceptivity, blood plasma IgE or peripheral blood eosinophil in
      adult population of Han nationality from Hubei province of China. METHODS:
      Polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP),
      tetra-primer PCR technique and restriction analysis were applied to identify the
      single nucleotide polymorphism. RESULTS: The allele frequency of eotaxin-3 +2497
      G, total levels of plasma IgE and peripheral blood eosinophil counts revealed the
      significant difference between control and allergic asthma group, that the P
      value was 0.011, 0.021 or 0.029 respectively. The allele frequency of eotaxin-3
      +77 T and total levels of plasma IgE showed to have no significant difference
      between control and allergic asthma group, that the P value was 0.824 and 0.473
      respectively. However, the peripheral blood eosinophil counts was significantly
      different between control and allergic asthma group, and the P value was 0.044.
      CONCLUSION: Single nucleotide polymorphism of eotaxin-3 +2497 is associated with
      the asthma susceptibility, peripheral eosinophil counts and total levels of
      plasma IgE in adult population from Hubei province, and polymorphism of +77 is
      associated with peripheral eosinophil counts.

PMID- 16604489
TI  - [Study on molecular genetic structure of Ael blood subgroup].
AB  - OBJECTIVE: To study the ABO allele molecular characteristics of Ael blood
      subgroup. METHODS: Five individuals of diagnosed as Ael blood subgroup were
      subjected to PCR amplify ABO alleles using four pairs of sequence-specific
      primers. Exon 6 and exon 7 at ABO locus of all samples were sequenced. An
      individual with AelB phenotype was chosen for further analysis of transcript
      structure of ABO gene. RESULTS: Sequence analysis indicated one Ael phenotype
      sample with reported Ael01 allele, one Ael phenotype sample with an Ael05 allele,
      and two AelB and one Ael individuals did not contain referred A allele, but
      contain O01 or O02 allele with 261G deletion. CONCLUSION: Molecular bases for the
      Ael have highly polymorphism. The mechanism responsible for the express weak A
      antigen of O allele with 261G deletion awaits to be elucidated.

PMID- 16604490
TI  - [A progress toward research on alternative splicing of genes in tumor cells].
AB  - Alternative splicing of pre-mRNA is an important mechanism for regulating gene
      function at the post-transcription level and for producing proteomic diversity in
      higher eukaryotes. The alternative splicing is regulated by the interaction
      between diverse cis-acting elements and trans-acting factors. Alternative
      splicing events of oncogenes, tumor suppressor genes and metastasis suppressor
      genes are associated with the initiation and development of human neoplasms. The
      protein isoforms sourced from alternative splicing take part in regulating the
      gene transcription, cell cycle, apoptosis of cells, and playing a role in tumor
      growth. It is possible for molecular therapy to target directly isoforms of
      protein produced by alternative splicing or to interfere with the process of
      alternative splicing.

PMID- 16604491
TI  - [Effect of R264C polymorphism in CYP19A1 gene on BRCA1/2-negative hereditary
      breast cancer from Shanghai population of China].
AB  - OBJECTIVE: Aromatase, encoded by CYP19A1, play an important role in estrogens
      biosynthesis from androgens. The present study is to investigate effect of R264C
      single nucleotide polymorphism in CYP19A1 gene on genetic susceptibility for
      hereditary breast cancer without BRCA1/2 mutant. METHODS: One hundred and
      fourteen BRCA1/2 -negative hereditary breast cancer patients from independent
      families and 121 age-matched healthy control subjects were analyzed. Genotype
      analysis was performed through polymerase chain reaction (PCR) and then DNA
      direct sequencing. The odd-ratios (OR) and 95% confidence intervals (CI) were
      calculated by unconditional Logistic regression model. RESULTS: The frequency of
      R264C single nucleotide polymorphism CC, CT and TT genotype in case group and
      controls was 84(77.8%), 22(20.4%), 2(1.8%) and 87(77.7%), 24(21.4%), 1(0.9%),
      respectively. CT genotype (OR=1.16, 95%CI: 0.53-2.55) and TT genotype (OR=1.44,
      95%CI: 0.12-17.15) did not confer a significantly increased risk for breast
      cancer. No significant association was found between T allele and susceptibility
      for breast cancer under analysis according to menopausal status and body mass
      index. CONCLUSION: R264C polymorphism in CYP19A1 gene is not a candidate locus
      for low penetrance breast cancer susceptibility in Shanghai group of Chinese
      population and not recommended in clinical genetic test. Homozygous T allele of
      R264C is not common in Shanghai group of Chinese population.

PMID- 16604492
TI  - [Detecting the polymorphism of methylenetetrahydrofolate reductase gene by
      denaturing high performance liquid chromatography].
AB  - OBJECTIVE: To establish a method for detecting the polymorphism of
      methylenetetrahydrofolate reductase gene (MTHFR). METHODS: The MTHFR was
      amplified, and the amplified products were detected by denaturing high
      performance liquid chromatography (DHPLC), and the amplified MTHFR was confirmed
      by sequencing and restriction enzyme digesting. RESULTS: A total of 334
      individuals of Han people in southern China were recruited in our study, and
      their polymorphisms of MTHFR were detected. The accurate rate of the DHPLC
      method, that was very sensitive with 100% detection rate available, was over 99%.
      The frequencies of CC, CT and TT genotypes were 56.9%, 38.3% and 4.8%
      individually, and the frequencies of T and C alleles were 23.95% and 76.05%
      individually. CONCLUSION: The DHPLC method can detect polymorphism of MTHFR
      rapidly, effectively and economically. And there is the existence of different
      MTHFR polymorphisms in area and race.

PMID- 16604493
TI  - [The expression of mutation p53 gene from circulating cancer cells of peripheral
      blood and the clinical significance in detecting the patients with colorectal
      cancer].
AB  - OBJECTIVE: To study the clinical significance of detecting p53 gene mutation
      expression in colorectal cancer cells of peripheral blood. METHODS: Flow
      cytometry (FCM) was used to detect p53 gene mutation expression in peripheral
      blood cancer cells of 128 patients with colorectal cancer. Experimental data were
      analyzed by SPSS (v.11.0) software. RESULTS: The lymph node metastasis showed the
      significant difference statistically (P<0.01) between p53 positive and negative
      expression in the colorectal cancer patients. The mutation p53 expression
      associated with existing histological differentiation (r=0.8476, P<0.05). A lymph
      node metastasis difference was observed between left and right colorectal cancers
      of mutation p53 positive expression. CONCLUSION: Detecting the mutation p53
      expression in cancer cells of peripheral blood might be helpful to the early
      diagnosis of colorectal cancer.

PMID- 16604494
TI  - [Cloning to rule out 10 candidate genes located in chromosome 12q24 for Charcot
      Marie-Tooth disease type 2L].
AB  - OBJECTIVE: To clone the disease-causing genes possibly existing in 6.8 cM
      distance between microsatellite markers D12S1720 and D12S1611 in chromosome 12q24
      for Charcot-Marie-Tooth disease type 2L (CMT2L). METHODS: Ten positional and
      functional candidate genes were chosen among all known genes in this locus region
      by bioinformatics inqury. Mutation detection was performed by sequencing the
      exons and intron-exon junctions of the candidate genes. RESULTS: Eleven sequence
      variations, that included 5 heterozygous and 6 homozygous variations, were
      detected in the exons and flanking areas of the 10 candidate genes. All the
      variations showed no co-segregation with disease phenotype. CONCLUSION: Ten
      candidate genes(TAOK3, RAB35, RPLP0, PXN, RNF10, RHOF, VPS33A, RSN, DENR, RNP24)
      were ruled out as the disease-causing gene for CMT2L. Ten single nucleotide
      polymorphisms (SNP) were reported for the first time.

PMID- 16604495
TI  - [Gene mutation analysis of a Chinese family with osteogenesis imperfecta].
AB  - OBJECTIVE: To study the gene mutation of collagen, type I, alpha 1 (COL1A1)
      associated with the clinical characterization of a Chinese family with type I
      osteogenesis imperfecta (OI). METHODS: Polymerase chain reaction, DNA sequencing
      and restriction endonuclaese analysis were used to check all the members in the
      family with OI and 50 normal control people for detecting the mutation of COL1A1
      gene. RESULTS: A 2461G>A (G821S) mutation was found and identified in COL1A1 gene
      of OI patients, to whom the individual clinical characterization was displayed,
      however. And the other members in the family with OI and the control did not have
      such gene mutation as 2461G>A. CONCLUSION: The mutation of COL1A1 gene is one of
      the OI etiologic causes in China. There is no simple universal linkage between
      such gene changes and OI phenotype, but which not only involved in the OI
      genotype but the genetic background as well.

PMID- 16604496
TI  - [A study on K469E polymorphism of ICAM1 gene and ICAM1 plasma level in patients
      with coronary heart disease].
AB  - OBJECTIVE: To study the linkage between K469E polymorphism of intercellular
      adhesion molecule 1(ICAM1) gene with ICAM1 plasma level and coronary heart
      disease (CHD) in Han population of China. METHODS: One hundred and sixty-four
      controls without CHD and 160 patients with CHD were enrolled in our study. By
      nested PCR with allele-specific oligonucleotide primers, all patients and
      controls were genotyped for the ICAM1 polymorphism. And the ICAM1 plasma level
      was measured by ELISA. RESULTS: In the patients with CHD, both K allele frequency
      and the plasma level of ICAM1 were higher than those in control (P<0.05). The
      individual with K allele had higher plasma level of ICAM1 than that without K
      allele (344.34+/-128.59 microg/L vs 303.54+/-108.74 microg/L, P=0.008). K allele
      enhanced the risk of CHD (P<0.01, OR=2.158, 95%CI: 1.250-3.727). There was the K
      allele cooperation with smoking in influencing the risk of CHD. CONCLUSION: There
      is the polymorphism of ICAM1 K469E gene in Han population of China, and the K
      allele may be a genetic factor influencing the risk of CHD.

PMID- 16604497
TI  - [The research on associating the single nucleotide polymorphism of CTLA-4 gene
      promoter region with idiopathic dilated cardiomyopathy].
AB  - OBJECTIVE: To investigate the expression of cytotoxic T lymphocyte associated
      antigen-4 (CTLA-4) in patients with idiopathic dilated cardiomyopathy (IDC) and
      to explore genetic susceptibility to IDC caused possibly by single nucleotide
      polymorphism (SNP) of CTLA-4 gene promoter. METHODS: PCR-restriction fragment
      length polymorphism techniques were used to analyze the SNPs of CTLA-4 gene at
      position -1772, -1661 and -318 in the promoter region. Serum sCTLA-4, IFN-gamma
      and IL-4 were tested by ELISA. RESULTS: sCTLA-4 levels of IDC patients were
      associated with the haplotype and genotype. Patients with -1772 TC genotype or 
      1772 TC -1661 AA, -1772 TC -1661 AG haplotypes had higher sCTLA-4 levels than
      patients with other haplotypes did. The frequency of -1772 TC genotype was
      significantly high in patients with low ejection factor(EF) values. Whereas the
      frequencies of -1661 G allele and -1661 GG genotype were lower in IDC patients.
      Levels of IL-4 were increased in IDC group. CONCLUSION: Patients with IDC have an
      aberrant expression of the CTLA-4 products, and the -1772 C/T and -1661 A/G
      polymorphisms. The two SNPs may function as genetic markers for disease
      susceptibility.

PMID- 16604498
TI  - [A linkage between beta-fibrinogen gene -148C/T polymorphism and cerebral
      infarction].
AB  - OBJECTIVE: To study the linkage between -148C/T polymorphism of beta-fibrinogen
      gene and plasma fibrinogen levels in patients with acute cerebral infarction.
      METHODS: One hundred and fifty-one patients with cerebral infarction and 101
      healthy individuals were enrolled in this trial. The beta-fibrinogen gene -148C/T
      polymorphism was analyzed by PCR-restriction fragment length polymorphism, and
      plasma fibrinogen levels were obtained from prothrombin time assay. RESULTS:
      Plasma fibrinogen levels of patients were significantly higher than those of
      controls (P<0.01). In both groups, T allele carriers had higher plasma fibrinogen
      levels than other those did (P<0.01); and the fibrinogen level difference was
      still significant if both groups was based on their sex (P<0.05). Divided by age,
      each group of the study cases has significant difference between two genotypes
      (P<0.05). T -148 allele frequency of the middle age case in study group was
      higher than that in control group (P<0.05). CONCLUSION: High plasma fibrinogen
      level is a risk factor to cerebral infarction. Plasma fibrinogen level is
      affected by -148C/T polymorphism of beta-fibrinogen gene. With or without other
      risk factors and environmental factors affecting, T allele increases plasma
      fibrinogen level and may be a heritable risk factor to cerebral infarction.

PMID- 16604499
TI  - [The correlation between ICAM-1 gene K469E polymorphism and coronary heart
      disease].
AB  - OBJECTIVE: To investigate the correlation between intercellular adhesion
      molecule1 (ICAM1) gene K469E polymorphism and coronary heart disease(CHD) in Han
      Chinese population. METHODS: Using the methods of polymerase chain reaction
      restrictive fragment length polymorphism (PCR-RFLP), 173 CHD patients and 141
      controls were analyzed for the polymorphism, genotype and allele distribution of
      ICAM1 gene K469E. RESULTS: The distribution of ICAM1 genotypes was in Hardy
      Weinberg equilibrium. The frequency of KK genotype in CHD group was significantly
      higher than that in control (64.2% vs 48.9%, P<0.01). Similarly, the frequency of
      K allele in CHD group was significantly higher than that in control (79.2% vs
      69.9%, P<0.01). With Logistic Regression Analysis ruling out the influences of
      age, gender and other CHD risk factor, the homozygous individual with KK genotype
      was 2.35 folds of KE or EE genotype one suffering from CHD (OR: 2.35, 95%CI: 1.03
      5.36, P<0.05). CONCLUSION: ICAM1 gene K469E polymorphism is associated with CHD
      risk of Han Chinese population, the K allele may serve as a genetic risk factor
      of coronary heart disease.

PMID- 16604500
TI  - [An evaluation for the function and significance concerned to alterations of P16
      3D structure with gene mutation in esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the clinicopathologic significance of P16 3D structure
      alterations in human esophageal squamous cell carcinoma(ESCC) so as to open a new
      approach for the research on clinical prevention and treatment of ESCC. METHODS:
      All three techniques of polymerase chain reaction-single strand comformation
      polymorphism (PCR-SSCP), DNA sequencing and computerized three-dimensional
      protein-modeling were applied to analyze and determine the gene mutations and the
      computerized 3D changes of P16 protein molecule. RESULTS: The p16 gene
      abnormality were detected from thirty-three cases of sixty-nine ESCC, among which
      twenty-six cases of ESCC showed the alterations of amino acid residues located
      within the P16 functional domains (classified as group M2), but other seven cases
      displayed the amino acid changes happened to beyond the domains and far from the
      p16-CDK4/6 binding site (defined as group M1). The statistical analysis revealed
      that the significant differences in lymph node metastasis, distance metastasis
      and stage of clinical were found between M2 and M1 groups (P<0.05). However no
      significant difference in sex, age, invasion depth of tumor was observed
      (P>0.05). CONCLUSION: The mutations of p16 gene will alter the P16 protein
      structure. The four ankyrin repeats are the critical regions of P16 protein. The
      abnormalities in the ankyrin repeats will seriously alter the 3D structure and
      the activity of P16 protein, with resulting in lymph node metastasis, distance
      metastasis, and clinically advanced stage. The above results render an authentic
      criterion to the selection of the clinical cases with high risk of metastasis.

PMID- 16604501
TI  - [A modified cytogenetic study for multiple myeloma].
AB  - OBJECTIVE: To evaluate the effect of modified culture method used to cytogenetic
      analysis and the clinically significance of chromosomal abnormalities to multiple
      myeloma (MM). METHODS: Mononuclear cells were isolated from bone marrow aspirate
      of 20 MM patients; and then cultured for 3 days without any cytokines, and 6 days
      in the presence of IL-6 (10 ng/mL) and GM-CSF (30 ng/mL) before RHG banding
      analysis; the remained part of aspirates were treated directly. Eight cases of
      iron deficiency anemia were taken as control. RESULTS: The experiment was failure
      in 2 cases because of blood clot, and another 2 cases could be analyzed only by
      direct method due to inadequate cells. The karyotype abnormalities were found
      from 4 cases of 16 available patients. Of them, three cases had complex
      karyotypes. The abnormalities were detected after 6 days culture with addition of
      cytokines. No abnormalities were detected from those groups of directly analysis
      and 3 day culture. Meantime, the clinical data showed that the patients with
      cytogenetic abnormalities were in stage III, and had a high percentage of MM
      cells (25%-56%) in their bone marrow, and also poor responses to prior
      chemotherapy. No cytogenetic abnormalities were found from control individuals in
      all groups. CONCLUSION: Extended culture in the presence of cytokines could
      improve the efficiency of cytogenetic analysis to MM. Complex karyotype was
      common cytogenetic abnormalities in MM patients with poor response to
      chemotherapy.

PMID- 16604502
TI  - [The genetic polymorphism of 9 short tandem repeat loci in Yi ethnic group of
      Yunnan in China].
AB  - OBJECTIVE: To study the short teadem repeat(STR) genetics structure of a Chinese
      Yunnan Yi racial group. METHODS: Genetic distributions for nine STR loci were
      determined based on STR gene scan marked by fluorescence. RESULTS: Sixty-nine
      alleles and 164 kinds of genotypes were detected and identified from 84 unrelated
      Yi racial individuals. The corresponding gene and genotype frequencies were in
      0.0060-0.5060 or 0.0119-0.4167 respectively. The expected and observed genotype
      frequencies of nine STR loci were in accordance with the Hardy-Weinberg
      equilibrium(P>0.05). The statistical analyses of nine STR loci showed that PIC
      was distributed in 0.5804-0.8777, H was in 0.6507-0.8002, DP was in 0.7976
      0.9558, EPP was in 0.5207-0.8386, except TPOX and THO1 loci. CONCLUSION: Above
      research data enrich the Chinese genetic database, and play an important role in
      Chinese genetic study and in forensic application.

PMID- 16604503
TI  - [Distribution of HLA-A, -B allele and haplotype polymorphism in the Tu
      nationality of Hubei province in China].
AB  - OBJECTIVE: To investigate the genetic diversity in Chinese populations. And HLA
      A, -B alleles and haplotypes of 190 unrelated healthy individuals of Tu
      nationality from Wufeng county Hubei province were identified for the associated
      studies of HLA gene polymorphism and disease. METHODS: The high-resolution typing
      methods--sequence-based typing(SBT) was used to define the most polymorphism of
      exons 2 and 3 of the HLA-A, -B locus alleles. The allele and haplotype
      frequencies were calculated by maximum likelihood estimation with Arlequin
      software. RESULTS: HLA-A, -B alleles were found to be in Hardy-Weinberg
      equilibrium(P>0.05). A total of 26 HLA-A and 41 HLA-B alleles were detected. The
      most frequent alleles were A*0201(0.16053), A*110101(0.14737),
      A*24020101(0.14211), B*4001(0.14737), B*4601(0.13947), followed by
      A*0207(0.08947), A*0206(0.08158), B*1301(0.07632), B*5801(0.08947),
      B*1501(0.09737). The frequencies of following alleles to be A*330301(0.05526),
      B*1502(0.05526), B*3501(0.05263) were all higher than 0.05. The extensive HLA-A-B
      haplotypes were observed, and the most common haplotypes were A*0202
      B*4001(0.04196), A*0201-B*4601(0.03625). CONCLUSION: In the present study, we
      first analyzed the HLA-A, B gene typing with SBT, all of these results will be
      the basic and reference data for Tu race, and also will have the applications
      available to trace the population migration, clinical organ transplantation,
      disease-associated study, HLA genetic feature and forensic identification.

PMID- 16604504
TI  - [Haplotypes of four single nucleotide polymorphisms in caspase-8, -10 genes in
      Han nationality of Zhejiang province in China].
AB  - OBJECTIVE: To investigate single nucleotide polymorphisms (SNPs) and the
      distribution of their haplotypes in caspase-8, -10 genes in Zhejiang Han
      nationality in China. METHODS: PCR, denaturing high-performance liquid
      chromatography (DHPLC) and DNA sequencing were used to detect the SNPs in the 2nd
      5th exons of caspase-10 gene, the 8th-10th exons of caspase-8 and their flanking
      sequences. Expectation Maximization (EM) algorithm was used for haplotype
      frequencies analysis and pairwise linkage disequilibrium (LD) test. RESULTS: (1)
      Two SNPs, A2823G and A12799G, were identified in caspase-10 gene, located in exon
      2 and exon 5 respectively. A12799G was newly found with low informativeness.
      Three SNPs were identified in caspase-8 gene; A43466G, G51484A and G52951A were
      located in exon 8, exon 9 and intron 9, respectively. They do not change the
      primary structure of the encoded protein. (2) Linkage equilibrium was observed
      between A2823G in caspase-10 gene and the three sites in caspase-8 gene. A43466G
      and G52951A, and G51484A and G52951A in caspase-8 gene were also in linkage
      equilibrium. Their coefficients of disequilibrium were near 0. Whereas strong
      linkage disequilibrium was observed between A43466G and G51484A, because its
      coefficient of disequilibrium was near 1. (3) A total of 11 haplotypes were
      estimated within A2823G in caspase-10 gene and three sites in caspase-8 gene. A
      2823/A-43466/G-51484/G-52951 was the main haplotype with a frequency of 0.3811. A
      2823/A-43466/G-51484/A-52951 was the second haplotype with a frequency of 0.2536.
      The polymorphism information content of their haplotypes was 0.7106. CONCLUSION:
      The SNPs of caspase-8, -10 genes in Han Chinese of Zhejiang could be parsed into
      at least three different haplotype blocks. The polymorphism information content
      can be improved by using haplotype analysis of several SNPs.

PMID- 16604505
TI  - [Fifteen short tandem repeat polymorphisms in Han race of North China].
AB  - OBJECTIVE: To research on the genetic polymorphism distributions of 15 short
      tandem repeat (STR) loci in Han race of North China and the genetic data of
      population genetics. METHODS: The capillary electrophoresis and five-color
      fluorescent multi-amplifying were applied to detect the genotypes of 15 STR loci
      in 597 unrelated Chinese Han individuals. RESULTS: No significant deviation from
      the Hardy-Weinberg Equilibrium was observed. High polymorphism was detected in
      the loci. Statistical analysis was carried out to obtain some parameters of
      forensic medicine. The heterozygosity of 15 loci was above 0.62. The values of
      discrimination power (DP) at 15 STRs ranged from 0.802 to 0.967. The values of
      excluding probability of paternity (EP) ranged from 0.320 to 0.697. The values of
      probability matching (Pm) ranged from 0.033 to 0.198. The fifteen loci showed an
      accumulated total discrimination power (TDP) more than 0.999999, a cumulative
      excluding probability of paternity (CEP) as 0.99999571, and total probability
      matching to be 8.93 x 10(-18). CONCLUSION: The data indicated that detecting
      combined 15 STRs is sensitive and reliable, and can be used to forensic and
      individual identification cases in Chinese group.

PMID- 16604506
TI  - [Polymorphisms of seven short tandem repeat loci: D1S2142, D1S3733, D2S1774,
      D3S2459, D21S1409, D21S1437 and D21S2055 of Chinese Han population in Chengdu].
AB  - OBJECTIVE: To obtain the data in polymorphism distribution of the seven short
      tandem repeat (STR) loci: D1S2142, D1S3733, D2S1774, D3S2459, D21S1409, D21S1437
      and D21S2055 of Chinese Han population in Chengdu, and evaluate the polymorphism
      data usefulness to the forensic science. METHODS: PCR, polyacrylamide gel
      electrophoresis (PAGE) and silver staining techniques were used to analyze the
      DNA samples from unrelated individuals of Chinese Han ethnic group in Chengdu.
      RESULTS: Eleven alleles and twenty-three genotypes were observed in D1S2142.
      Eight alleles and nineteen genotypes were observed in D1S3733. Eight alleles and
      fifteen genotypes were observed in D2S1774. Seven alleles and nineteen genotypes
      were observed in D3S2459. Six alleles and twelve genotypes were observed in
      D21S1409. Nine alleles and twenty-six genotypes were observed in D21S1437. Twenty
      alleles and seventy-seven genotypes were observed in D21S2055. The genotype
      distributions of the seven STR loci showed no deviation from the Hardy-Weinberg
      equilibrium. The parentage testing of 50 cases revealed an autosomal codominant
      inheritances and no mutations happened to seven STR loci. CONCLUSION: These data
      indicate that D1S2142, D1S3733, D2S1774, D3S2459, D21S1409, D21S1437 and D21S2055
      have good polymorphism, with high probability of exclusion and probability of
      discrimination power as well as being loci available as the candidate genetic
      markers to forensic parentage testing and personal identification.

PMID- 16604507
TI  - [Genetic polymorphisms of Penta D and E loci in Korean racial Chinese of Yanbian
      area in China].
AB  - OBJECTIVE: To analyze genetic polymorphisms of Penta D and E loci in Korean
      racial Chinese of Yanbian area. METHODS: One hundred unrelated individuals of
      Korean racial Chinese were analyzed by methods of PCR and restriction fragment
      length polymorphism. RESULTS: Eight alleles and 22 genotypes were observed from
      Penata D locus, and 16 alleles and 35 genotypes were observed from Penta E locus.
      CONCLUSION: The distribution of two locus genotypes in Korean racial Chinese of
      Yanbian area met Hardy-Weinberg equilibrium. And the obtained data can be used to
      individual identity, paternity testing and the study of Korean ethnic group of
      Chinese population.

PMID- 16604508
TI  - [Polymorphism of vitamin D receptor gene Fok I in Mongolian population of China].
AB  - OBJECTIVE: To investigate the polymorphism distribution of vitamin D receptor
      (VDR) gene Fok I in Mongolian population of China. METHODS: Polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to
      analyze three genotypes FF, Ff and ff in the start codon of VDR gene (Fok I) in
      unrelated normal healthy Mongolian individuals of China. RESULTS: In the
      population, we obtained the allelic frequencies of 57% and 43% for (F) and (f)
      allele and the percentage of genotypes FF, Ff and ff to be 31%, 52%, and 17%
      respectively. CONCLUSION: The polymorphism frequency and distribution of this VDR
      gene Fok I in Mongolian population of China exhibit its own characteristics.

PMID- 16604509
TI  - [With genechip technique to investigate HLA-DQB1 gene polymorphisms in south and
      north regions of China].
AB  - OBJECTIVE: To research and compare HLA-DQB1 gene frequency(GF) and polymorphism
      distribution between south and north population of Chinese in China. METHODS:
      Combining PCR-sequence specific primers(SSP) and sequence specific
      oligonucleotide probe(SSOP) techniques and DNA Microarray Kit for HLA-DQB1 Low
      Res Genotyping from Shenzhen Yi-Shengtang Biological LTD. Co. was used to type
      HLA-DQB1 gene polymorphisms of 700 individuals living in south China and 320
      individuals in north China. RESULTS: We inspected 10 alleles of HLA-DQB1 and got
      a series of comprehensive and accurate statistic data. CONCLUSION: It is tested
      that HLA-DQB1*02, 05, 0601, 0602, 0603 gene frequencies are different
      obviously(P<0.05) between south and north Chinese. And those data will be useful
      to kinds of research associated with disease relevant and anthropology research.

PMID- 16604510
TI  - [Analysis of HLA-DRB1 allele polymorphism in the Fujian Han nationality
      population of China].
AB  - OBJECTIVE: To investigate the HLA-DRB1 allele polymorphism in Fujian Han
      nationality population. METHODS: Six hundred and twenty individual samples
      collected from unrelated Fujian Han population were subjected to genotyping using
      oligonucleotide microarray technique. And the allele frequencies of HLA-DRB1 were
      calculated and compared with other populations. RESULTS: Fourteen HLA-DRB1
      alleles of Fujian Han population were detected. The gene frequencies ordered from
      high to low were HLA-DRB1*9, 12, 15, 4, 8 respectively. CONCLUSION: The HLA-DRB1
      distribution of Fujian Han population shares some genetic characters with
      southern Chinese Han populations, but these characters differ from northern
      Chinese populations.

PMID- 16604511
TI  - Quantitative analysis of allele imbalance supports atypical ductal hyperplasia
      lesions as direct breast cancer precursors.
AB  - It remains unclear whether hyperplastic breast lesions, especially with atypia,
      are cancer precursors or markers of increased cancer risk. Quantified comparisons
      of genomic alterations in coexisting lesions could address this question.
      Therefore, we examined allele imbalance (AI), also known as loss of
      heterozygosity (LOH), at 20 microsatellite markers on nine chromosome arms, in
      DNA from 106 samples microdissected from 17 randomly selected cancer-containing
      breast specimens: 13 simple (DH) and 45 atypical ductal hyperplastic (ADH)
      lesions, 30 in situ (DCIS) and 18 invasive ductal carcinomas (IDC). Data were
      analysed using regression models and generalized estimating equations. We found
      that AI increased as histology became more aberrant and varied with histology
      across the chromosome arms (p<0.0001). ADH had more AIs on 1q (p=0.03) and 16q
      (p=0.02) and fewer AIs on 17p (p=0.06) and 17q (p<0.0001) than on other arms. In
      cancers, AIs remained high on 1q and 16q, and became frequent on 17p and 17q.
      Concordance between AIs in ADHs and cancers exceeded the 50% expected if the
      lesions were separate clones in 16/20 (80%) ADHs (p=0.05), from 9/11 (82%) cases
      (p=0.03), and involved 41/51 (80%) evaluable markers (p=0.05). The occurrence of
      any AI in ADH predicted greater AI (p=0.009) and possibly lower grade (p=0.05) in
      coexisting cancers. Nevertheless, ADHs were not genetically identical to cancers
      or to each other. We found AIs discordant between ADHs and cancers (always on 1q
      and 16q), AIs unique to ADH (usually on 11q) and some genetic heterogeneity among
      coexisting ADHs. We conclude that ADH lesions are genetically advanced, with
      frequent alterations on 1q and 16q, and are often direct cancer precursors. Their
      global genetic characteristics predict features of cancers in the same breast.
      Nevertheless, the genetic heterogeneity detected suggests that hyperplasias and
      cancers may arise on a field at generalized increased cancer risk.

PMID- 16604512
TI  - Brachyury and chordoma: the chondroid-chordoid dilemma resolved?
AB  - Chordoma, and its relationship to the notochord, has intrigued many researchers
      over the last two centuries. In particular, the morphological overlap with
      cartilaginous tumours is striking, and developmental biology has shown a tight
      relationship between cartilage and the notochord. This is reflected in the
      expression of common genes in chordoid and chondroid tumours. Wide gene
      expression analyses have led to the identification of key molecules that might
      play a crucial role in the pathogenesis of chordoma. Brachyury, a key factor in
      notochord fate, is significantly differentially expressed in chordoma. This not
      only gives insight into the histogenesis of this tumour but may also point
      towards new diagnostic tools in the differential diagnosis between chordoid and
      chondroid tumours.

PMID- 16604513
TI  - Royal crown-shaped electride Li3-N3-Be containing two superatoms: new knowledge
      on aromaticity.
AB  - The structure and aromaticity of a royal crown-shaped molecule Li(3)-N(3)-Be are
      studied at the CCSD(T)/aug-cc-pVDZ level. This molecule is a charge-separated
      system and can be denoted as Li(3) (2+)N(3) (3-)Be(+). It is found that the Li(3)
      (2+) ring exhibits aromaticity mainly because the Li(3) (2+) ring can share the
      pi-electron with the N(3) (-3) ring. The 4n+2 electron counter rule can be
      satisfied for the Li(3) (2+) subunit if the shared pi valence electron of N(3) (3
      ) subunit is also taken into account. This new knowledge on aromaticity of a ring
      from the interactions between subunits is revealed first time in this paper.
      Li(3)-N(3)-Be can be also regarded as a molecule containing two superatoms (Li(3)
      and N(3)), which may be named as a "superomolecule." Li(3)-N(3)-Be is a new metal
      nonmetal-metal type sandwich complex. The N(3) (3-) trianion in the middle
      repulses the electron clouds of the two metal subunits (mainly to the Li(3)
      superatom) to generate an excess electron, and thus Li(3)-N(3)-Be is also an
      electride. This phenomenon of the repulsion results in: (a) the HOMO energy level
      increased, (b) the electron cloud in HOMO distended, (c) the area of the negative
      NICS value extended, and (d) the VIE value lowered. So the superomolecule Li(3)
      N(3)-Be is not only a new metal-nonmetal-metal type sandwich complex but also a
      new type electride, which comes from the interaction between the alkali superatom
      (Li(3)) and the nonmetal superatom (N(3)).

PMID- 16604514
TI  - The polarizable continuum model (PCM) interfaced with the fragment molecular
      orbital method (FMO).
AB  - The polarizable continuum model (PCM) for the description of solvent effects is
      combined with the fragment molecular orbital (FMO) method at several levels of
      theory, using a many-body expansion of the electron density and the corresponding
      electrostatic potential, thereby determining solute (FMO)-solvent (PCM)
      interactions. The resulting method, denoted FMO/PCM, is applied to a set of model
      systems, including alpha-helices and beta-strands of alanine consisting of 10,
      20, and 40 residues and their mutants to charged arginine and glutamate residues.
      The FMO/PCM error in reproducing the PCM solvation energy for a full system is
      found to be below 1 kcal/mol in all cases if a two-body expansion of the electron
      density is used in the PCM potential calculation and two residues are assigned to
      each fragment. The scaling of the FMO/PCM method is demonstrated to be nearly
      linear at all levels for polyalanine systems. A study of the relative stabilities
      of alpha-helices and beta-strands is performed, and the magnitude of the
      contributing factors is determined. The method is applied to three proteins
      consisting of 20, 129, and 245 residues, and the solvation energy and
      computational efficiency are discussed.

PMID- 16604516
TI  - Nucleoplasmin facilitates reprogramming and in vivo development of bovine nuclear
      transfer embryos.
AB  - Successful cloning by somatic cell nuclear transfer (NT) involves an oocyte
      driven transition in gene expression from an inherited somatic pattern, to an
      embryonic form, during early development. This reprogramming of gene expression
      is thought to require the remodeling of somatic chromatin and as such, faulty
      and/or incomplete chromatin remodeling may contribute to the aberrant gene
      expression and abnormal development observed in NT embryos. We used a novel
      approach to supplement the oocyte with chromatin remodeling factors and
      determined the impact of these molecules on gene expression and development of
      bovine NT embryos. Nucleoplasmin (NPL) or polyglutamic acid (PGA) was injected
      into bovine oocytes at different concentrations, either before (pre-NT) or after
      (post-NT) NT. Pre-implantation embryos were then transferred to bovine recipients
      to assess in vivo development. Microinjection of remodeling factors resulted in
      apparent differences in the rate of blastocyst development and in pregnancy
      initiation rates in both NPL- and PGA-injected embryos, and these differences
      were dependent on factor concentration and/or the time of injection. Post-NT NPL
      injected embryos that produced the highest rate of pregnancy also demonstrated
      differentially expressed genes relative to pre-NT NPL embryos and control NT
      embryos, both of which had lower pregnancy rates. Over 200 genes were upregulated
      following post-NT NPL injection. Several of these genes were previously shown to
      be downregulated in NT embryos when compared to bovine IVF embryos. These data
      suggest that addition of chromatin remodeling factors to the oocyte may improve
      development of NT embryos by facilitating reprogramming of the somatic nucleus.

PMID- 16604517
TI  - Global gene expression profiles associated with retinoic acid-induced
      differentiation of embryonal carcinoma cells.
AB  - We have evaluated the effects of retinoic acid (RA) treatment of F9 embryonal
      carcinoma (EC) cells, which induces differentiation into primitive endoderm, on
      gene expression patterns. F9 cells were exposed to RA in culture, and global
      expression patterns were examined with cDNA-based microarrays at early (8 hr) and
      later times (24 hr) after exposure. Of the 1,176 known transcripts examined, we
      identified 57 genes (4.8%) that were responsive to RA at 8 and/or 24 hr: 35 were
      induced, 20 were repressed, and 2 were differentially regulated at these time
      points. To determine if our results were dependent on the array technology
      employed, we also evaluated the response to RA at 24 hr with oligonucleotide
      based arrays. With these more dense arrays (12,488 genes), we identified an
      additional 353 RA-regulated genes (2.8%): 173 were upregulated and 180 were
      downregulated. Thus, a total of 410 genes regulated by RA were identified with
      roughly equivalent numbers induced or repressed. Although the expression of many
      genes found on both array platforms was consistent, the results for some genes
      were disparate. Quantitative PCR studies on a subset of these genes supported the
      results obtained with the cDNA arrays. Our results confirmed the regulation of
      several known RA-responsive genes and we also identified a number of genes not
      previously known to be RA-responsive. Those novel genes that were induced
      presumably contribute to the cellular processes required for a shift from
      proliferation to differentiation, whereas those new genes that were downregulated
      may possibly contribute to the maintenance of cell proliferation.

PMID- 16604518
TI  - Generation of a mouse with conditionally activated signaling through the BMP
      receptor, ALK2.
AB  - BMP signaling plays pleiotropic roles in various tissues. Transgenic mouse lines
      that overexpress BMP signaling in a tissue-specific manner would be beneficial;
      however, production of each tissue-specific transgenic mouse line is labor
      intensive. Here, using a Cre-loxP system, we generated a conditionally
      overexpressing mouse line for BMP signaling through the type I receptor ALK2
      (alternatively known as AVCRI, ActRI, or ActRIA). By mating this line with Cre
      expression mouse lines, Cre-mediated recombination removes an intervening floxed
      lacZ expression cassette and thereby permits the expression of a constitutively
      active form of Alk2 (caAlk2) driven by a ubiquitous promoter, CAG. Tissue
      specificity of Cre recombination was monitored by a bicistronically expressed
      EGFP following Alk2 cDNA. Increased BMP signaling was confirmed by ectopic
      phosphorylation of SMAD1/5/8 in the areas where Cre recombination had occurred.
      The conditional overexpression system described here provides versatility in
      investigating gene functions in a tissue-specific manner without having to
      generate independent tissue-specific transgenic lines.

PMID- 16604519
TI  - A new "Logicle" display method avoids deceptive effects of logarithmic scaling
      for low signals and compensated data.
AB  - BACKGROUND: In immunofluorescence measurements and most other flow cytometry
      applications, fluorescence signals of interest can range down to essentially
      zero. After fluorescence compensation, some cell populations will have low means
      and include events with negative data values. Logarithmic presentation has been
      very useful in providing informative displays of wide-ranging flow cytometry
      data, but it fails to adequately display cell populations with low means and high
      variances and, in particular, offers no way to include negative data values. This
      has led to a great deal of difficulty in interpreting and understanding flow
      cytometry data, has often resulted in incorrect delineation of cell populations,
      and has led many people to question the correctness of compensation computations
      that were, in fact, correct. RESULTS: We identified a set of criteria for
      creating data visualization methods that accommodate the scaling difficulties
      presented by flow cytometry data. On the basis of these, we developed a new data
      visualization method that provides important advantages over linear or
      logarithmic scaling for display of flow cytometry data, a scaling we refer to as
      "Logicle" scaling. Logicle functions represent a particular generalization of the
      hyperbolic sine function with one more adjustable parameter than linear or
      logarithmic functions. Finally, we developed methods for objectively and
      automatically selecting an appropriate value for this parameter. CONCLUSIONS: The
      Logicle display method provides more complete, appropriate, and readily
      interpretable representations of data that includes populations with low-to-zero
      means, including distributions resulting from fluorescence compensation
      procedures, than can be produced using either logarithmic or linear displays. The
      method includes a specific algorithm for evaluating actual data distributions and
      deriving parameters of the Logicle scaling function appropriate for optimal
      display of that data. It is critical to note that Logicle visualization does not
      change the data values or the descriptive statistics computed from them.

PMID- 16604520
TI  - Comparison of CID spectra of singly charged polypeptide antibiotic precursor ions
      obtained by positive-ion vacuum MALDI IT/RTOF and TOF/RTOF, AP-MALDI-IT and ESI
      IT mass spectrometry.
AB  - Various classes of polypeptide antibiotics, including blocked linear peptides
      (gramicidin D), side-chain-cyclized peptides (bacitracin, viomycin, capreomycin),
      side-chain-cyclized depsipeptides (virginiamycin S), real cyclic peptides
      (tyrocidin, gramcidin S) and side-chain-cyclized lipopeptides (polymyxin B and E,
      amfomycin), were investigated by low-energy collision induced dissociation (LE
      CID) as well as high-energy CID (HE-CID). Ion trap (IT) based instruments with
      different desorption/ionization techniques such as electrospray ionization (ESI),
      atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) and
      vacuum MALDI (vMALDI) as well as a vMALDI-time-of-flight (TOF)/curved field
      reflectron instrument fitted with a gas collision cell were used. For optimum
      comparability of data from different IT instruments, the CID conditions were
      standardized and only singly charged precursor ions were considered.
      Additionally, HE-CID data obtained from the TOF-based instrument were acquired
      and compared with LE-CID data from ITs. Major differences between trap-based and
      TOF-based CID data are that the latter data set lacks abundant additional loss of
      small neutrals (e.g. ammonia, water) but contains product ions down to the
      immonium-ion-type region, thereby allowing the detection of even single amino
      acid (even unusual amino acids) substitutions. For several polypeptide
      antibiotics, mass spectrometric as well as tandem mass spectrometric data are
      shown and discussed for the first time, and some yet undescribed minor components
      are also reported. De novo sequencing of unusually linked minor components of
      (e.g. cyclic) polypeptides is practically impossible without knowledge of the
      exact structure and fragmentation behavior of the major components. Finally, the
      described standardized CID condition constitutes a basic prerequisite for
      creating a searchable, annotated MS(n)-database of bioactive compounds. The
      applied desorption/ionization techniques showed no significant influence on the
      type of product ions (neglecting relative abundances of product ions formed)
      observed, and therefore the type of analyzer connected with the CID process
      mainly determines the type of fragment ions.

PMID- 16604521
TI  - Sodium butyrate-treated embryonic stem cells yield hepatocyte-like cells
      expressing a glycolytic phenotype.
AB  - Embryonic stem cells serve as a promising technology to obtain specific cell
      types for a number of biomedical applications. Because traditional techniques,
      such as embryoid body formation result in a wide array of differentiated cells
      such as hepatic, neuronal, and cardiac lineages, strategies have been utilized
      which favor cell-specific differentiation to generate more uniformity. In the
      present study, we have investigated the use of sodium butyrate in a monolayer
      culture configuration to mediate hepatocyte differentiation of murine embryonic
      stem cells. Several functional assays used to characterize hepatocyte function
      (viz. urea secretion, intracellular albumin content, cytokeratin 18, and glycogen
      staining) were used to analyze the differentiating cell population, suggesting
      the presence of an enriched population of hepatocyte-like cells. Since mature
      hepatocytes mediate energy metabolism predominantly through oxidative means as
      opposed to hepatocyte precursors, which are primarily glycolytic, we have
      performed a kinetic analysis of glycolytic and functional capacity to
      characterize the differentiated cells. In conjunction with mitochondrial mass and
      activity measurements, we show that Na-butyrate-mediated differentiated cells
      mediate energy metabolism predominantly through glycolysis. This metabolic and
      mitochondrial characterization can assist in evaluating stem cell differentiation
      and may prove useful in identifying key regulatory molecules in mediating further
      differentiation.

PMID- 16604522
TI  - Fabrication of endothelialized tube in collagen gel as starting point for self
      developing capillary-like network to construct three-dimensional organs in vitro.
AB  - A possible strategy for creating three-dimensional (3D) tissue-engineered organs
      in vitro with similar volumes to the primary organs is to develop a capillary
      network throughout the constructs to provide sufficient oxygenation and nutrition
      to the cells composing them. Here, we propose a novel approach for the creation
      of a capillary-like network in vitro, based on the spontaneous tube-forming
      activity of vascular endothelial cells (ECs) in collagen gel. We fabricated a
      linear tube of 500 microm in diameter, the inner surface of which was filled with
      bovine carotid artery vascular endothelial cells (BECs), in type I collagen gel
      as a starting point for the formation of a capillary-like network. The BECs
      exposed to a medium containing vascular endothelial growth factor (VEGF) migrated
      into the ambient gel around the tube. After 2 weeks of VEGF exposure, the
      distance of the migration into the ambient gel in the radial direction of the
      tube reached approximately 800 microm. Cross-sections of capillary-like
      structures composed of the migrating BECs, with a lumen-like interior space, were
      observed in slices of the gel around the tube stained with hematoxylin-eosin
      (H&E). These results demonstrate that this approach using a pre-established tube,
      which is composed of ECs, as a starting point for a self-developing capillary
      like network is potentially useful for constructing 3D organs in vitro.

PMID- 16604525
TI  - Comparative proteomic analysis to study molecular events during gonad development
      in mice.
AB  - Sex determination represents a critical bifurcation in the road of embryonic
      development. It is based on a finely regulated network of gene activity, as well
      as protein-protein interactions and activation or silencing of signaling
      pathways. Despite the identification of a number of critical genes, many aspects
      of the molecular cascade that drives the differentiation of the embryonic gonad
      into either a testis or an ovary remain poorly understood. To identify new
      proteins involved in this cascade, we employed two-dimensional gel
      electrophoresis and mass spectrometry to compare the protein expression profiles
      of fetal mouse testes and ovaries. Three proteins, hnRPA1, TRA1, and HSC71, were
      found to be expressed in a male-specific manner and this expression was confirmed
      by real-time reverse transcriptase polymerase chain reaction (RT-PCR) and in situ
      hybridization. Moreover, HSC71 was found to be hyperphosphorylated in male
      compared to female gonads, emphasizing the advantage of the proteomic approach in
      allowing the detection of posttranslational modifications.

PMID- 16604526
TI  - Transgenic mouse for conditional, tissue-specific Cox-2 overexpression.
AB  - We constructed a cyclooxygenase-2 (Cox-2) conditional overexpression transgenic
      mouse (Cox-2 COE). The transgene contains a CAG promoter driving the Cox-2 and
      humanized Renilla luciferase (hRL) coding regions, linked by an internal
      ribosomal entry site. The promoter is followed by a loxP-flanked sequence
      containing enhanced green fluorescent protein (EGFP), a neomycin selection
      cassette, and a transcriptional/translational STOP sequence. In the presence of
      Cre recombinase the loxP-flanked sequence is excised. Cox-2/hRL expression can be
      monitored repeatedly and noninvasively in vivo by imaging hRL activity. To
      demonstrate conditional Cox-2 and hRL expression, a nonreplicating adenovirus
      carrying Cre recombinase (Ad.CMV.Cre) was injected intravenously; hepatic Cox-2
      expression and hRL signal were elevated. Cox-2 COE embryonic fibroblasts express
      both Cox-2 and hRL following Ad.CMV.Cre infection. PGE(2) production is also
      increased following Ad.CMV.Cre infection of Cox-2 COE embryo fibroblasts. Cox-2
      COE mice should be valuable for the study of Cox-2 overexpression in
      cardiovascular disease, acute and chronic inflammatory responses,
      neurodegenerative diseases, and cancer.

PMID- 16604527
TI  - Inhibin alpha-iCre mice: Cre deleter lines for the gonads, pituitary, and
      adrenal.
AB  - To expand our knowledge of reproductive function, Cre lines to conditionally
      knockout essential genes in the mouse gonads were generated. Three transgenic
      lines of inhibin-alpha-iCre mice were designed by fusing the mouse inhibin-alpha
      promoter with a codon-improved Cre recombinase (iCre). alpha-iCre-line-3
      expressed high levels of Cre in Sertoli and Leydig cells of the testis and low
      levels in other tissues, making line 3 an appropriate deleter line for genes
      expressed in somatic cells of the testis. In contrast, alpha-iCre-line-1
      expressed high levels of Cre in granulosa and theca cells of the ovary and very
      low levels in other tissues, making line 1 a suitable deleter line for genes
      expressed in somatic cells of the ovary. A third line, alpha-iCre-line-2, had low
      levels of Cre in the gonads but high levels in anterior pituitary and adrenal
      medulla. These lines could be useful to understand reproduction and other
      processes by establishing conditional knockout mouse models.

PMID- 16604528
TI  - In vivo imaging and differential localization of lipid-modified GFP-variant
      fusions in embryonic stem cells and mice.
AB  - The visualization of live cell behaviors operating in situ combined with the
      power of mouse genetics represents a major step toward understanding the
      mechanisms regulating embryonic development, homeostasis, and disease progression
      in mammals. The availability of genetically encoded fluorescent protein
      reporters, combined with improved optical imaging modalities, have led to
      advances in our ability to examine cells in vivo. We developed a series of lipid
      modified fluorescent protein fusions that are targeted to and label the secretory
      pathway and the plasma membrane, and that are amenable for use in mice. Here we
      report the generation of two strains of mice, each expressing a spectrally
      distinct lipid-modified GFP-variant fluorescent protein fusion. The CAG::GFP-GPI
      strain exhibited widespread expression of a glycosylphosphatidylinositol-tagged
      green fluorescent protein (GFP) fusion, while the CAG::myr-Venus strain exhibited
      widespread expression of a myristoyl-Venus yellow fluorescent protein fusion.
      Imaging of live transgenic embryonic stem (ES) cells, either live or fixed
      embryos and postnatal tissues demonstrated that glycosylphosphatidyl inositol-
      and myristoyl-tagged GFP-variant fusion proteins are targeted to and serve as
      markers of the plasma membrane. Moreover, our data suggest that these two lipid
      modified protein fusions are dynamically targeted both to overlapping as well as
      distinct lipid-enriched compartments within cells. These transgenic strains not
      only represent high-contrast reporters of cell morphology and plasma membrane
      dynamics, but also may be used as in vivo sensors of lipid localization.
      Furthermore, combining these reporters with the study of mouse mutants will be a
      step forward in understanding the inter- and intracellular behaviors underlying
      morphogenesis in both normal and mutant contexts.

PMID- 16604529
TI  - Changes in the natural history of nonsmall cell lung cancer (NSCLC)--comparison
      of outcomes and characteristics in patients with advanced NSCLC entered in
      Eastern Cooperative Oncology Group trials before and after 1990.
AB  - BACKGROUND: Demographic factors and treatment regimens were evaluated in relation
      to differences in outcome between patients with advanced nonsmall cell lung
      cancer (NSCLC) who were diagnosed and treated on Eastern Cooperative Oncology
      Group Phase II and III trials from 1981 to 1990 and from 1991 to 2000. METHODS:
      In this retrospective analysis, 6 advanced NSCLC trials were identified between
      1981 and 1990, and 3 trials were identified after 1990. Patient characteristics
      (n = 3398 patients) and other clinical outcomes were analyzed, including
      progression-free survival (PFS) and overall survival (OS). RESULTS: Patients who
      entered on trials after 1990 more likely were women, received a cisplatin
      containing regimen, had a performance status of 0 or 1, had Stage IIIB (vs. Stage
      IV) disease, had tumors with adenocarcinoma histology, had weight loss < or =
      10%, and had pulmonary-only metastases (although more total metastases and brain
      metastases) compared with patients who were diagnosed before 1990. OS was longer
      post-1990 than pre-1990 (8.2 months vs. 5.8 months pre-1990), and PFS was longer
      post-1990 (3.5 months vs. 2.6 months pre-1990; P<.001 for both). In addition, the
      median interval from the date of disease progression to death increased by nearly
      62% in the later decade. CONCLUSIONS: Improved survival in more recent NSCLC
      trials was explained in part by the enrollment of patients with more favorable
      prognostic factors. A change in the natural history of the disease was reflected
      by some of these changes, including increased numbers of women with the disease
      and changes in the patterns of metastases. Changes in eligibility criteria also
      accounted for some improvements in prognostic factors and improved second line
      therapies in the later decade. Thus, the survival improvements are likely to be
      multifactorial, with improved therapies also playing a major role.

PMID- 16604530
TI  - A unique device for controlled electrospinning.
AB  - The purpose of this research was to develop a system for controlled
      electrospinning of fibro-porous scaffolds for tissue engineering applications and
      to use this system to assess mesh architecture sensitivity to manufacturing
      parameters. The intent was to achieve scaffolds with well-controlled fiber
      diameters and inter-fiber spacing. To accomplish these objectives, a custom,
      closed-loop controlled, electrospinning system was built. The system was unique
      in that it had a collection surface that was independent of the electrodes. The
      system allowed independent manipulation and analysis of a number of manufacturing
      parameters: distance between the electrodes, distance from the nozzle to the
      collection surface, applied voltage, temperature of the melt, collection surface
      dielectric strength, and collection surface area. Morphological analysis of
      fabricated meshes showed that all test parameters significantly affected fiber
      diameter and inter-fiber spacing. Further, contrary to what is generally accepted
      in the electrospinning literature, voltage and temperature (inversely related to
      viscosity) were not the most significant parameters. Features of the collection
      surface, including dielectric strength and surface area, were more significant.
      This dominance is, in part, a reflection of the unique electrospinning system
      used. The collection surface, which was not connected to either of the
      electrodes, substantially altered the electric field between the electrodes.
      Using the developed controlled electrospinning system, thermoplastic polyurethane
      meshes with fiber diameters ranging from 5 to 18 microm with variability less
      than 1.8% were made; inter-fiber spacing ranged from 4 to 90 microm with
      variability less than 20.2%. The system has potential use in biomedical
      applications where meshes with controlled fiber diameter and inter-fiber spacing
      are of interest.

PMID- 16604531
TI  - Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates
      cell proliferation through CD147.
AB  - BACKGROUND: Although overexpression of cyclophilin A (CypA) is associated with
      several types of cancer, its role in pancreatic cancer has not been studied. In
      this study the expression of CypA and its receptor CD147 on pancreatic cancer was
      determined as well as the effect of exogenous CypA on pancreatic cancer cell
      proliferation. METHODS: The expression of CypA and CD147 in human pancreatic
      cancer cell lines and tissues was determined with real-time reverse transcriptase
      polymerase chain reaction (RT-PCR), Western blot, and immunostaining. Cell
      proliferation in response to CypA was performed by [3H]thymidine incorporation
      assay. Phosphorylation of MAPK and cytokine secretion profiles in pancreatic
      cancer cells were determined by using the Bio-Plex phosphoprotein assay and
      cytokine assay. RESULTS: Pancreatic cancer cell lines expressed significantly
      higher levels of CypA and CD147 than normal human pancreatic ductal epithelium
      (HPDE) cells. Expression of CypA and CD147 was also substantially higher in human
      pancreatic adenocarcinoma tissues than those in normal pancreatic tissues.
      Addition of exogenous CypA significantly stimulated pancreatic cancer cell
      proliferation in a dose-dependent manner and this effect was effectively blocked
      by pretreatment with anti-CD147 antibody. In addition, CypA activated ERK1/2 and
      p38 MAPK signaling pathways and increased the secretion of 2 key cytokines IL-5
      and IL-17 in Panc-1 cells. CONCLUSIONS: The expression of CypA and CD147 was
      significantly increased in both pancreatic cancer cell lines and tissues.
      Exogenous CypA promotes pancreatic cancer cell growth, which may be mediated
      through the interaction with CD147 and the activation of ERK1/2 and p38 MAPKs.

PMID- 16604532
TI  - Silicon-substituted hydroxyapatite thin films: effect of annealing temperature on
      coating stability and bioactivity.
AB  - The effect of annealing temperature on the physicochemical and biological
      characteristics of magnetron cosputtered silicon-substituted hydroxyapatite
      (SiHA) thin coatings was studied. Annealing is required to transform as-sputtered
      amorphous films into crystalline coatings. A nanocrystalline, single-phase
      apatite structure was achieved for coatings heated to 600 or 700 degrees C and,
      with increasing annealing temperature, the crystallite size increased. Small
      crystallites were found to be more soluble in the physiological environment but,
      at the same time, were able to induce early formation of a new apatite layer. A
      human osteoblast-like (HOB) cell model was used to evaluate the performance of
      these annealed SiHA coatings. HOB cells attached and grew well on coatings and,
      after 42 days in culture, a mineralization process was observed to be taking
      place, with evidence of calcium phosphate minerals throughout the extracellular
      matrix. Our findings indicated that an annealing temperature of 600 degrees C is
      sufficient to achieve crystalline SiHA coatings and exhibiting good chemical
      stability and bioactivity.

PMID- 16604533
TI  - Glutathione-S-transferase-green fluorescent protein fusion protein reveals slow
      dissociation from high site density beads and measures free GSH.
AB  - BACKGROUND: Glutathione, a ubiquitous tripeptide, is an important cellular
      constituent, and measurement of reduced and oxidized glutathione is a measure of
      the redox state of cells. Glutathione-S-transferase (GST) fusion proteins bind
      naturally to beads derivatized with glutathione, and elution of such bead-bound
      fusion proteins with buffer containing millimolar glutathione is a commonly used
      method of protein purification. Many protein-protein interactions have been
      established by using GST fusion proteins and measuring binding of fusion protein
      binding partners by GST pulldown assays, usually monitored by Western blot
      methodology. METHODS: Dextran beads suitable for flow cytometry were derivatized
      with glutathione. A fusion protein of GST and green fluorescent protein was used
      to define kinetic and equilibrium binding characteristics of GST fusion proteins
      to glutathione beads. Free glutathione competes with this binding, and this
      competition was used to measure free glutathione concentration. RESULTS: A 10
      microl assay can measure 5 microl of 20 microM glutathione (100 pmol glutathione)
      in 2 h by flow cytometry. This concentration is two orders of magnitude lower
      than cellular glutathione concentrations, and three orders of magnitude lower
      than affinity chromatography eluates. One important result is that by generating
      high site density, the GST fusion proteins can be constrained to the surface of
      one bead without hopping to the next bead in multiplex assays. CONCLUSIONS:
      Glutathione in cellular lysates and GST-fusion protein affinity chromatography
      eluates can be measured by flow cytometry. Many interactions between GST fusion
      proteins and their fluorescent binding partners should be quantifiable by flow
      cytometry. Although a system may have the disadvantage that it has a low affinity
      and a correspondingly quick off-rate in solution, it may remain on beads if the
      site density can be increased to offer a slow apparent off rate.

PMID- 16604534
TI  - Division of the male rat rhabdosphincter into structurally and functionally
      differentiated parts.
AB  - In order to understand the structure-function relationship in the male rat
      rhabdosphincter, the 3D structure of the striated muscle and associated dense
      connective tissue was reconstructed from representative serial sections cut from
      the proximal urethra harboring the muscle. The 3D structure was correlated with
      electromyography (EMG) of the rhabdosphincter, urodynamic parameters (bladder
      pressure and flow rate), and longitudinal contraction force of the proximal
      urethra. The muscular component of the rhabdosphincter consisted of a homogeneous
      population of the fast-twitch-type fibers. In the cranial part, striated muscle
      formed a complete ring encircling the urethra, deferent ducts, and ducts from
      seminal vesicles and prostatic lobes. Toward the middle part, the amount of
      densely packed connective tissue lacking type III collagen increased anteriorly
      and posteriorly and penetrated the muscular ring that became divided first
      posteriorly and then anteriorly into two symmetrical halves. In the caudal part,
      a thin midsagittal dense connective tissue septum remained posteriorly. EMG
      recordings suggested that the rhabdosphincter muscle was functionally divided
      into two parts. Unlike the cranial and middle parts, the caudal part did not show
      the first depolarization peak. It appears that rapid oscillatory oblique-to
      circular muscular contractions proceeding in craniocaudal direction in the
      cranial and middle part draw the anterior wall supported by arch-like dense
      connective tissue closer to the posterior wall supported by a more rigid
      rhomboidal raphe. Longitudinal contractions of the urethra are possibly evoked
      from the proximal and caudal parts of rhabdosphincter. These could lead to
      simultaneous increase in urethral pressure ensuring rapid urine flow rate. The
      caudal part could augment the opening of urethral lumen during oscillatory
      voiding.

PMID- 16604535
TI  - Superquenching as a detector for microsphere-based flow cytometric assays.
AB  - BACKGROUND: Fluorescent conjugated polymers display high fluorescence quantum
      yields and enhanced sensitivity to quenching (superquenching) by oppositely
      charged quenchers through energy or electron transfer. Fluorescent polymers and
      their quenchers are used in bead-based biosensor applications where the polymers
      are coated on particles. In this work, we investigate a detection method that
      utilizes superquenching on microspheres, which can be used for flow cytometric
      assays. METHODS: Microspheres were coated with the fluorescent cationic
      polyelectrolyte poly(p-phenylene-ethynylene) (PPE), and its superquenching by
      9,10-anthraquinone-2,6-disulfonic acid (AQS) was examined by fluorometric methods
      in presence and in absence of a barrier to superquenching in the form of an
      anionic lipid bilayer. RESULTS: Flow cytometry detected superquenching of PPE on
      microspheres (MS-PPE) by AQS where high levels of reduction in fluorescence were
      observed. Adding different concentrations of AQS to MS-PPE yielded a Stern-Volmer
      quenching constant of 0.8x10(6) M-1. While forming an anionic lipid bilayer
      around the MS-PPE acted as a barrier to superquenching by AQS, disrupting the
      lipid bilayer allowed superquenching to take place. CONCLUSIONS: The sensitivity
      of flow cytometry in detecting fluorescence of microspheres and the amplified
      quenching sensitivity of fluorescent conjugated polymers both offer advantages
      over other fluorometric methods and conventional quenching detection. This study
      used superquenching of fluorescent polymers as a new tool in flow cytometry, thus
      combining the advantages offered by both method and detector. In addition, we
      employed the formation and the disruption of a supported lipid bilayer in
      mediating superquenching to offer new biosensing applications.

PMID- 16604536
TI  - Multiplex analysis of circulating cytokines in the sera of patients with
      different clinical forms of visceral leishmaniasis.
AB  - BACKGROUND: The clinical spectrum of visceral leishmaniasis (VL), a chronic
      intracellular parasitic disease, ranges from a subclinical, asymptomatic
      infection to severe clinical disease (kala-azar). In experimental leishmaniasis,
      mice that have a Th1 response to infection tend to have limited disease while a
      Th2 response is associated with disease progression. Humans with VL most often
      have mixed rather than polarized responses. However, most clinical studies have
      used methods that require a relatively large sample volume, thus limiting their
      scope. Measuring multiple cytokine levels in blood samples using a multiplexed
      microsphere assay (MMA) may be useful to further evaluate the Th1/Th2 paradigm in
      humans. METHODS: Bangladeshi individuals (n=120) living in an area endemic for VL
      were categorized into one of the five clinical categories. Sera from these
      individuals were measured for levels of IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL
      12, IFN-gamma, and TNF-alpha by multiplexed microsphere cytokine immunoassay.
      RESULTS: Circulating IL-8, IL-10, and IL-12 differed significantly among the
      clinical groups. Persons with kala-azar demonstrated the highest median levels of
      IL-8 and IL-10 but lower median levels of IL-12. CONCLUSIONS: The MMA for
      cytokines is an extremely time-and sample-efficient method for characterizing
      circulating cytokine levels in visceral leishmaniasis patients.

PMID- 16604539
TI  - Effect of microsphere binding site density on the apparent affinity of an
      interaction partner.
AB  - BACKGROUND: Flow cytometric microsphere-based binding assays can be used to
      measure molecular interactions with high sensitivity. We have used multiplexed
      microsphere technology to explore the effect that binding site density has on the
      apparent affinity of a soluble interaction partner. METHODS: The interaction of a
      nuclear receptor, peroxisome proliferator-activated receptor gamma ligand binding
      domain (PPARgamma LBD), with a synthetic peptide derived from a nuclear receptor
      coactivator protein, PPARgamma coactivator-1 alpha (PGC-1alpha), is the
      interacting system being studied. The density of this peptide coupled to
      fluorescently unique microsphere populations is varied by co-incubating the
      biotinylated peptide and avidin-coated microsphere populations with increasing
      the amounts of free D-biotin. The discrete-density peptide-coupled microsphere
      populations are combined to conduct a multiplexed binding experiment with Alexa
      532-labeled PPARgamma LBD, in the absence or presence of a small molecule ligand.
      RESULTS: As the immobilized binding site density of PGC-1alpha peptide on
      fluorescent microspheres is increased the measured apparent affinity for
      PPARgamma LBD is increased. CONCLUSIONS: The density of binding sites immobilized
      to a surface has a pronounced effect on the apparent affinity for soluble binding
      partners. By controlling and varying the binding site density it is possible to
      increase the sensitivity of an interaction assay. In multiplexed assay formats it
      should be possible to normalize intrinsically unequal binding interactions by
      individually optimizing the binding site density of the immobilized interaction
      partner. However, to quantitatively measure intrinsic affinities of molecular
      interactions, low binding site densities are required and multivalent reagents
      must be avoided.

PMID- 16604538
TI  - Microsphere-based protease assays and screening application for lethal factor and
      factor Xa.
AB  - BACKGROUND: Proteases regulate many biological pathways in humans and are
      components of several bacterial toxins. Protease studies and development of
      protease inhibitors do not follow a single established methodology and are mostly
      protease specific. METHODS: We have created recombinant fusion proteins
      consisting of a biotinylated attachment sequence linked to a GFP via a protease
      cleavage site to develop a multiplexable microsphere-based protease assay system.
      Using the proteases lethal factor and factor Xa, we performed kinetic experiments
      to determine optimal conditions for inhibitor screens and detect known inhibitors
      using the HyperCyt flow cytometry system. RESULTS: We have demonstrated specific
      cleavage of lethal factor and factor Xa substrates, optimized screening
      conditions for these substrates, shown specific inhibition of the proteases, and
      demonstrated high throughput detection of these inhibitors. CONCLUSIONS: The
      assay developed here is adaptable to any site-specific protease, compatible with
      high throughput flow cytometry systems, and multiplexable. Coupled with flow
      cytometry, which provides continuous time resolution and intrinsic resolution of
      free vs. bound fluorophores, this assay will be useful for high throughput
      screening of protease inhibitors in general and could simplify assays designed to
      determine protease mechanism.

PMID- 16604540
TI  - Simultaneous detection of porcine proinflammatory cytokines using multiplex flow
      cytometry by the xMAP technology.
AB  - BACKGROUND: Multiplex flow cytometry is in widespread use for detection of
      cytokines in human samples. However, no report on the measurement of porcine
      cytokines using this method has previously been published. We report on the
      detection of the porcine proinflammatory cytokines TNF-alpha, IL-8, and IL-1beta
      by the xMap-assay for multiplex flow cytometry. METHODS: Commercially available
      antibodies to porcine cytokines were used as capture antibodies by attaching them
      to goat anti-mouse IgG coated microspheres with different fluorescent signatures.
      By the use of biotinylated detection antibodies and SAv-PE the amount of
      cytokines bound to the spheres were measured. Experiments were performed to
      determine the limits of detection and the amount of crossreactivity in buffer,
      serum, and plasma, using spiking with recombinant porcine cytokines. RESULTS: The
      limit of detection ranged from 0.18 to 12 ng/ml. Generally, the detection limit
      was higher in serum and plasma, than in buffer. No crossreactivity between
      reagents was found. CONCLUSIONS: Porcine proinflammatory cytokines can be
      detected utilizing this method with satisfactory detection limits, and no
      crossreaction between the reagents involved.

PMID- 16604537
TI  - Multiplexed and microparticle-based analyses: quantitative tools for the large
      scale analysis of biological systems.
AB  - While the term flow cytometry refers to the measurement of cells, the approach of
      making sensitive multiparameter optical measurements in a flowing sample stream
      is a very general analytical approach. The past few years have seen an explosion
      in the application of flow cytometry technology for molecular analysis and
      measurements using microparticles as solid supports. While microsphere-based
      molecular analyses using flow cytometry date back three decades, the need for
      highly parallel quantitative molecular measurements that has arisen from various
      genomic and proteomic advances has driven the development in particle encoding
      technology to enable highly multiplexed assays. Multiplexed particle-based
      immunoassays are now common place, and new assays to study genes, protein
      function, and molecular assembly. Numerous efforts are underway to extend the
      multiplexing capabilities of microparticle-based assays through new approaches to
      particle encoding and analyte reporting. The impact of these developments will be
      seen in the basic research and clinical laboratories, as well as in drug
      development.

PMID- 16604541
TI  - Multiplexed flow cytometric analyses of pro- and anti-inflammatory cytokines in
      the culture media of oxysterol-treated human monocytic cells and in the sera of
      atherosclerotic patients.
AB  - BACKGROUND: Some oxysterols are identified in atheromatous plaques and in plasma
      of atherosclerotic patients. We asked whether they might modulate cytokine
      secretion on human monocytic cells. In healthy and atherosclerotic subjects, we
      also investigated the relationships between circulating levels of C-reactive
      protein (CRP), conventional markers of hyperlipidemia, some oxysterols (7beta
      hydroxycholesterol, 7-ketocholesterol, and 25-hydroxycholesterol), and various
      cytokines. METHODS: Different flow cytometric bead-based assays were used to
      quantify some cytokines (IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL
      12, IL-13, IL-17, G-CSF, GM-CSF, IFN-gamma, MCP-1, MIP-1beta, or TNF-alpha) in
      the culture media of oxysterol-treated U937 and THP-1 cells, and in the sera of
      healthy and atherosclerotic subjects. CRP and markers of hyperlipidemia were
      determined with routine analytical methods. Oxysterols were quantified by gas
      chromatography/mass spectrometry. Flow cytometric and biochemical methods were
      used to measure IL-8 mRNA levels, intracellular IL-8 content, and protein
      phosphorylation in the mitogenic extracellular kinase/extracellular signal
      regulated kinase1/2 (MEK/ERK1/2) signaling pathway. RESULTS: All oxysterols
      investigated are potent in vitro inducers of MCP-1, MIP-1beta, TNF-alpha, and/or
      IL-8 secretion, the latter involving the MEK/ERK1/2 cell signaling pathway. In
      healthy and atherosclerotic subjects, no relationships were found between
      cytokines (IL-8, IL-1beta, IL-6, IL-10, TNF-alpha, IL-12, and MCP-1), CRP,
      conventional markers of hyperlipidemia, and oxysterols. However, in patients with
      arterial disorders of the lower limbs, small but statistically significant
      differences in the circulating levels of CRP, TNF-alpha, and IL-10 were observed
      comparatively to healthy subjects and according to the atherosclerotic stage
      considered. CONCLUSIONS: Flow cytometric bead-based assays are well adapted to
      measure variations of cytokine secretion in the culture media of oxysterol
      treated cells and in the sera of healthy and atherosclerotic subjects. They
      underline the in vitro proinflammatory properties of oxysterols and may permit to
      distinguish healthy and atherosclerotic subjects, as well as various
      atherosclerotic stages.

PMID- 16604542
TI  - Role of the osteoclast in cranial suture waveform patterning.
AB  - This study investigates the role of bone resorption in defining interdigitations
      characteristic of cranial suture waveform. Male mice from the CD-1 (ICR)
      background were analyzed at six age groups (n = 5 mice per group) in order to
      study the ontogenetic changes of osteoclast counts using tartrate-resistant acid
      phosphatase-stained histological sections of sagittal sutures. Additionally, the
      complexity of suture lines were measured ectocranially from the same age groups
      (n = 5 per group) using image capture and fractal geometry (ruler dimension
      method). The results suggest that osteoclast resorption is a contributor to
      suture patterning. Specifically, osteoclasts show the greatest activity along
      concave suture regions at 42 and 84 days (Kruskal-Wallis test statistic = 14.9; P
      < or = 0.01). This coincides with significant increases incrementally in suture
      complexity as measured with fractal dimension at 42 and 84 days of age (ANOVA F
      statistic = 19.84; P < or = 0.001). In congruence with these data, mice given
      osteoclast-depleting injections of alendronate show a decrease in sagittal suture
      complexity. Data from this experiment indicate a positive relationship between
      suture complexity and osteoclast count (P < 0.01; r = 76%). Increases in suture
      complexity and osteoclast activity occur after peak rates of cranial width growth
      and coincide with weaning and the transition to a hard chow diet. These data
      demonstrate osteoclasts along the bone margin of the cranial suture and also
      indicate that sutures attain their complex shape at the same age when osteoclast
      number is highest along concave suture margins, underscoring the role of
      osteoclasts in generating the suture waveform pattern.

PMID- 16604543
TI  - Cytology of pancreatic acinar cell carcinoma.
AB  - Acinar cell carcinoma (ACC) of the pancreas is extremely uncommon and its
      cytologic features have rarely been described. We describe the cytologic features
      of cases we have seen, review the literature regarding its cytologic features and
      discuss the pitfalls that may be encountered and the use of immunohistochemistry
      for its diagnosis. We searched our databases for all cases of histologically
      confirmed pancreatic ACC which had undergone prior fine needle aspiration (FNA)
      of the primary pancreatic lesion. The clinical histories, radiographic and
      sonographic findings, cytologic features, original cytologic diagnoses, and final
      histologic diagnoses were reviewed. Four cases of pancreatic ACC were found that
      had undergone FNA prior to histologic confirmation of the diagnoses. They were
      from 2 men and 2 women aged 50-75 yr. All masses were in the head of the
      pancreas, 2 had apparent peri-pancreatic adenopathy and 1 had an apparent liver
      metastasis. On review, all 4 had had diagnostic material on cytology samples.
      Original cytologic diagnoses included "acinar cell carcinoma," "pancreatic
      endocrine tumor," "favor neuroendocrine tumor, low-grade" and "non-diagnostic
      specimen." The cytologic features included small to moderate-sized loose groups
      with numerous single cells, prominent acinar formation, little anisonucleosis and
      prominent nucleoli. The cytologic features showed significant overlap with those
      of pancreatic endocrine tumors.

PMID- 16604544
TI  - Ascaris lumbricoides eggs in vaginal wet smear.

PMID- 16604546
TI  - Infarcted intraductal papilloma of the breast: cytologic features with stage of
      infarction.
AB  - Fine-needle aspiration cytology (FNAC) is being employed with increasing
      frequency for the pre-operative diagnostic workup of breast lesions. Although
      most cases show morphologic features very characteristic of specific entities,
      rare lesions with infarcted breast can cause problems in interpretation. We
      present cytologic findings in seven cases of an infarcted intraductal papilloma
      of the breast (IDPB) that was diagnosed by FNAC, and we also report the
      correlation of cytological features and stages of infarcted IDPB. In the early
      stage of infarction, numerous degenerative cells and necrotic debris were
      demonstrated. Isolated degenerative cells showed columnar, spindle, polygonal and
      fiber-like cells, with coagulated and smudged nuclei. Ghost cells were also seen.
      Extensive necrosis was demonstrated with a few sheets of ductal cells in the mid
      stage of infarction. In the late stage of infarction, clusters of fibroblasts,
      ductal cells and necrotic debris were found. Knowledge of the characteristic
      cytologic pattern in different stages of infarcted IDPB may be helpful to suggest
      the probable pre-operative diagnosis of those lesions. Familiarity with this
      entity is important in preventing misdiagnosis of malignancy.

PMID- 16604548
TI  - Worst case scenario: carcinoma of unknown origin.

PMID- 16604549
TI  - Endocervical curetting vs. endocervical brushing as case finding methods.
AB  - This paper focuses on the performance of endocervical curettage (ECC) and
      intensive endocervical brushing (ECB) (comprising two or more brushings of the
      endocervix with liquid-based cytology and cell-block examination) in the course
      of colposcopic examination for abnormal gynecological cytology. To assess their
      relative effectiveness in disease detection, we reviewed the outcomes of 1,824
      colposcopic biopsy collections from women who had an index cytology diagnosis of
      LSIL or higher. Our intent was to gauge the relative success of ECC and ECB as
      case-finding procedures in relation to (1) the original cytological diagnosis and
      (2) the highest (most abnormal) histological diagnosis of the colposcopy study.
      Our purpose was to determine whether ECB could effectively replace ECC. One
      thousand five hundred and seven cases of LSILs or higher cases included an ECC
      along with two or more colposcopic biopsies and 317 cases included an ECB. ECBs
      were collected into a liquid fixative and processed as both cytology and cell
      block specimens; whereas, ECCs were processed according to standard histological
      techniques. We found that intensive ECB recapitulates the highest diagnosis of
      the colposcopy study about 5-8 times as often as that of ECC. Moreover, when
      calculating the proportion of positive outcomes, we found that cases examined
      with biopsy and ECC discovered fewer women with CIN 2 or higher among both LSIL
      and HSIL index cytologies as compared with those of cases examined with biopsy
      and ECB (9.2% vs. 16.8% for LSIL and 63.7% vs. 72.2% for HSIL cases); and, more
      negative outcomes were seen among women evaluated with biopsy plus ECC than those
      with biopsy plus ECB (11.3% vs. 8.1% for LSIL and 4.7% vs. 1.4% for HSIL cases).
      Our findings suggest that the colposcopic study is optimized when it is performed
      in conjunction with ECB as opposed to ECC, and that intensive ECB may be superior
      to ECC.

PMID- 16604550
TI  - Cytological features of prostatic intraepithelial neoplasia.
AB  - Fine-needle aspiration cytology (FNAC) is an acknowledged method for diagnosing
      prostate cancer. False-positive results are uncommon, but concerns have been
      raised that prostatic intraepithelial neoplasia (PIN) could be misinterpreted as
      carcinoma. Therefore, we attempted to describe cytological features of PIN. Cells
      were scraped from macroscopically normal areas of 177 radical prostatectomy
      specimens, smeared and Giemsa-stained. Histological slides from these areas were
      reviewed, and 17 samples with high-grade PIN and with no invasive cancer were
      selected. Smears from 17 invasive cancers were used for comparison. Cancer showed
      high cellularity and dissociation, while PIN smears only contained a few clusters
      of atypical cells. Pronounced nuclear atypia, prominent or multiple nucleoli and
      mucin were more common in cancer, while cytoplasmic granules, crystalloids and
      cluster size did not distinguish between PIN and cancer. In conclusion, PIN
      should not be diagnosed by FNAC alone. However, a highly cellular smear with
      pronounced atypia seems to preclude PIN.

PMID- 16604551
TI  - Is bacterial vaginosis associated with squamous intraepithelial lesion of the
      uterine cervix?
AB  - The objective of this study was to analyze the association between bacterial
      vaginosis (BV) and squamous intraepithelial lesion (SIL). Pap smears were
      analyzed to verify the presence of BV and SIL. One hundred and ten women with SIL
      comprised the study group, while 110 women with no cytological abnormalities
      served as controls. BV was similarly present in women of both groups: 18% of
      women with SIL and 12% of women without SIL. Results were also similar when the
      grade of SIL was taken into consideration. BV was detected in 16% of women with
      low-grade SIL and in 12% of women in the control group, while a higher rate of BV
      (33%) was found among women with high-grade SIL in comparison to the controls
      (12%). This difference, however, was not statistically significant. BV tended to
      be more common among women with high-grade SIL than in women with no cytological
      abnormalities.

PMID- 16604552
TI  - Can hamartoma of the breast be distinguished from fibroadenoma using fine-needle
      aspiration cytology?
AB  - In an attempt to determine if it is possible to distinguish hamartoma of the
      breast from fibroadenoma using fine-needle aspiration cytology, we reviewed the
      cytological slides of 13 histopathologically confirmed cases of hamartoma of the
      breast and compared them with the cytological features of 13 histologically
      confirmed fibroadenomas. In each case, we studied the epithelial and stromal
      features. Cytologic characteristics were retrospectively evaluated in a
      semiquantitative manner. In conclusion, the finding of intact lobular units and a
      relative paucity of stroma may suggest the diagnosis of hamartoma.

PMID- 16604553
TI  - Does Hurthle cell lesion/neoplasm predict malignancy more than follicular
      lesion/neoplasm on thyroid fine-needle aspiration?
AB  - Thyroid fine-needle aspiration (FNA) is a standard procedure for the clinical
      triage of thyroid nodules. The diagnosis of an adequately sampled thyroid FNA is
      generally grouped into three categories: benign, malignant, and indeterminate.
      The latter group usually includes follicular neoplasm, follicular lesion, and
      sometimes a more specific diagnosis such as Hurthle cell neoplasm or follicular
      lesion/neoplasm with Hurthle cell change. Whether a FNA diagnosis of Hurthle cell
      lesion/neoplasm (HLN) denotes a worse clinical outcome than follicular
      lesion/neoplasm (FLN) remains controversial. A cohort of 303 thyroid FNA cases
      with follow-up thyroidectomy in our institutes was identified, with the follow-up
      excision diagnosis compared to the FNA diagnosis in order to address this issue.
      Of this cohort, 87 cases had an FNA diagnosis of HLN while 216 cases had a
      diagnosis of FLN. Upon excision, the FNA diagnosis of HLN group had 14 cases of
      goiter/nodular hyperplasia (16%), 46 cases of adenoma (12 follicular adenoma
      (14%) and 34 cases of Hurthle cell adenoma (39%)), and 27 cases of carcinoma
      (31%, 12 papillary carcinoma and 15 Hurthle cell carcinoma). The FLN group had 74
      cases of goiter/nodular hyperplasia (34.3%), 8 cases of Hashimoto thyroiditis
      (3.7%), 73 cases of follicular adenoma (33.8%), one case of granular cell tumor,
      and 60 cases of carcinoma (27.8%, 46 papillary carcinoma, 12 follicular
      carcinoma, and 1 Hurthle cell carcinoma and 1 parathyroid carcinoma) upon
      excision. There is no significant difference in predicting cancer between the two
      cytology diagnosis groups (HLN versus FLN, 31% versus 27.8%, P = 0.5771). When
      sorting all the cases by the surgical diagnosis, while comparable for age at
      diagnosis, the cancer group having the higher proportion of male patients than
      the non-cancer group (28.7% versus 16.7%, P = 0.0259). Hurthle cell carcinoma
      patients are typically older than patients with other cancer diagnoses (59 versus
      44, P = 0.0077). Our results suggest that an FNA diagnosis of HLN does not
      predict more malignancy than FLN. Males and older patients with a HLN FNA
      diagnosis carry a higher risk of Hurthle cell carcinoma upon thyroidectomy.

PMID- 16604554
TI  - Liesegang rings in renal cyst fluid.

PMID- 16604555
TI  - Fine-needle aspiration cytology of thymic basaloid carcinoma: case studies and
      review of the literature.
AB  - We report the features in fine-needle aspiration biopsy (FNAB) of thymic basaloid
      carcinomas. This is a rare neoplasm, of which there are only three documented in
      our hospital files. To the best of our knowledge, this is the first fine-needle
      aspiration (FNA) report on basaloid carcinoma of the thymus. This is a tumor in
      which the FNA diagnosis is difficult and the differential diagnosis is broad. We
      describe the cytologic features encountered in the three cases, and
      immunohistochemical and ultrastructural findings so as to raise awareness of this
      entity in the differential diagnosis of thymic neoplasms on FNABs. The cases
      studied included three male patients, aged 73, 65, and 50, who presented with
      anterior mediastinal masses, with no primary tumor elsewhere. FNAB was performed
      on two cases, followed by thymectomy. One case, additionally, had metastasis to a
      cervical lymph node, and the other two were associated with thymic cysts. The
      diagnoses on all three cases were thymic basaloid carcinoma.

PMID- 16604556
TI  - Dysbacteriosis and squamous (pre)neoplasia of immigrants and Dutch women as
      established in population-based cervical screening.
AB  - We examined the statistical relationships between dysbacteriosis and
      (pre)neoplasia related to age and ethnicity from the cervical screening of almost
      half a million smears. Data from 445,080 smears were coded according to KOPAC
      (the Dutch national cervical smear coding system) with nine grades. Prevalence
      per 100,000 smears and relative risks (RR) were calculated for dysbacteriosis and
      for squamous abnormalities. Patients were stratified by their probable country of
      origin. Dutch women had an RR of 0.92 for dysbacteriosis. Surinamese women had
      the highest RR for dysbacteriosis (RR = 2.36) and Moroccan women had the lowest
      (RR = 1.00). The same trends were seen for the risks of squamous abnormalities.
      The data for Turkish women follow the patterns of those for Surinamese women. The
      RR of dysbacteriosis is highest at 50 yr (1.28) and lowest at 35 yr (0.86). When
      dysbacteriotic and non-dysbacteriotic smears were compared, dysbacteriosis was
      observed more frequently in smears with squamous abnormalities (4.1% vs. 2.2%).
      Dysbacteriosis may warrant more intensive cytological surveillance and changes in
      lifestyle.

PMID- 16604557
TI  - Tigroid background in fine-needle aspiration cytology of clear cell sarcoma.
AB  - Clear-Cell Sarcoma (CCS) is a rare malignant soft tissue tumor of young adults
      that often metastasizes to the lymph nodes. The fine needle aspirate cytology
      (FNAC) findings of CCS have been described previously and it is included in the
      cytological category of polygonal soft tissue tumors. We describe the cytology of
      a case of CCS, with emphasis on the so called "tigroid background." Though this
      tigroid background is a nonspecific feature and has been described in various
      other tumors, to the best of our knowledge, it has not been described in CCS.
      This feature may be useful in the recognition of CCS.

PMID- 16604558
TI  - FNA of pilomatrixoma: smear vs. cell block.

PMID- 16604559
TI  - Serous effusions in malignant lymphomas: a review.
AB  - Serous effusions are a common complication of lymphomas. Although the frequency
      of pleural effusion is 20-30% in non-Hodgkin's lymphoma (NHL) and Hodgkin's
      disease (HD), the involvement of peritoneal and pericardial cavities is uncommon.
      Among lymphoma subtypes, T-cell neoplasms, especially the lymphoblastic
      lymphomas, more frequently involve the serous fluids. The thoracic duct
      obstruction and impaired lymphatic drainage appear to be the primary mechanism
      for pathogenesis of pleural effusion in HD and direct pleural infiltration is the
      predominant cause in NHL. There is wide variation in rate of positive cytologic
      findings of NHL in pleural effusion (22.2-94.1%). Cytologic features of specific
      lymphoma subtypes such as lymphoblastic lymphoma, follicular center cell
      lymphoma, including Burkitt-type lymphoma, marginal zone lymphoma, MALT lymphoma,
      and anaplastic large-cell lymphoma, etc., have been described in the literature.
      The differential diagnostic problems of lymphomas in serous effusions include
      reactive lymphocytoses, early involvement by lymphomatous process, small round
      cell tumors (SRCT), and presence of look-alike of Reed-Sternberg cells. To
      overcome these difficulties, various ancillary studies, including
      immunocytochemistry (ICC), morphometry, flow cytometry (FCM), and
      cytogenetics/molecular genetics (PCR, in-situ hybridization, and Southern
      blotting), have been performed on effusion specimens. ICC not only distinguishes
      lymphomas from reactive lymphocytoses and SRCTs, it significantly modifies the
      morphologic diagnosis to achieve a better classification of lymphomas. Combined
      morphology and immunophenotyping by FCM, has a sensitivity as well as specificity
      of 100%. Morphometry also distinguishes reactive lymphocytoses from malignant
      lymphoma with a high degree of sensitivity (>85%) and specificity (>95%).
      Limitations of individual ancillary techniques can be overcome by using multiple
      parameters. Although lymphomas rarely present as serous effusions without the
      involvement of other thoracic and extrathoracic sites, a small group of lymphomas
      called primary effusion lymphomas (PEL) exhibit exclusive or dominant involvement
      of serous cavities, without a detectable solid tumor mass. This body cavity based
      lymphoma (BCBL) is a distinct clinicopathologic entity and is found predominantly
      in AIDS patients with preexisting Kaposi sarcoma. In the absence of obstructive
      or infiltrative tumor mass, its pathogenesis has been attributed to stimulation
      by vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF),
      leading to vascular leakage. Cytomorphologically, PEL is usually a large-cell
      lymphoma, which appears to bridge features of large-cell immunoblastic and
      anaplastic large-cell lymphoma (ALCL). Most of these cases comprise a unique
      subgroup of B-cell lymphoma, with features of both high-grade anaplastic and B
      immunoblastic lymphoma, but T-cell and/or natural killer cell immunophenotypes
      are described. Its association with various viral DNAs has been studied in detail
      by molecular techniques. Pleural effusion due to lymphomas, either primary or
      otherwise, is considered as one of the factors adversely influencing overall
      survival. The presence of pleural effusion at the time of presentation is not
      only associated with extremely poor outcome of lymphomas, it is also a predictor
      of disease relapse after chemotherapy and decreased survival. When the patients
      of lymphomatous pleural effusions with and without mediastinal mass present in
      respiratory distress, thoracocentesis is the initial diagnostic and therapeutic
      choice in these patients. In such situations, cytology along with ancillary
      studies not only gives a quick diagnosis of lymphoma, but also offers
      prognostically significant information such as classification of lymphomas, its
      grade and immunophenotype, and presence/absence of viral DNAs and tumor lysis
      syndrome.

PMID- 16604560
TI  - Alternaria spp. in the Pap test of a 25 year-old woman.

PMID- 16604561
TI  - Amiodarone lung toxicity in a cardiac transplant candidate initially diagnosed by
      fine-needle aspiration: cytologic, histologic, and electronmicroscopic findings.
AB  - A cardiac transplant candidate with ischemic cardiomyopathy developed bilateral
      small parenchymal opacities in lower lobes of the lung. A fine-needle aspiration
      (FNA) was performed that revealed changes characteristic of amiodarone toxicity.
      Subsequently performed lung biopsies and electron microscopic studies confirmed
      the initial FNA diagnosis. The patient has been successfully transplanted with
      marked improvement in his clinical findings. This is the first case of amiodarone
      lung toxicity where the diagnosis was initially suggested based on the FNA
      findings. We also describe the clinical, cytological, histological, and electron
      microscopic (EM) findings of amiodarone-related pulmonary toxicity and provide a
      review of the literature.

PMID- 16604562
TI  - Sexual dimorphism in digit length ratios in two lizard species.
AB  - Sexual dimorphism in digit length ratios has been reported for humans, a few
      other mammals, and two bird species. This dimorphism is thought to arise via an
      interaction between the prenatal exposure of the embryo to sex hormones and the
      Hox genes, which are highly conserved among vertebrates and control the
      development of both the appendices, including fingers and toes, and the
      urogenital system. In this study, we report on sexual dimorphism in 2D:3D, 2D:4D,
      and 3D:4D contralateral ratios of the forelimbs in two species of oviparous
      lizards, the common wall lizard (Podarcis muralis) and the tree skink (Mabuya
      planifrons), as measured on museum specimens. We found that male P. muralis had a
      larger 2D:4D ratio on both sides and larger 2D:3D ratio on the left side than
      females, whereas in M. planifrons, males had lower 2D:3D ratios than females on
      the left side. The two species show opposite patterns of sexual dimorphism in
      body size, males being larger than females in P. muralis, and the reverse in M.
      planifrons, suggesting that interspecific variation of sex differences in digit
      ratios could be associated with sex-specific growth trajectories. There was a
      limited evidence for directional asymmetry in digit ratios. Therefore, our
      findings provide the first evidence that digit ratios are sexually dimorphic in
      any reptile species and are consistent with the idea that the genetic link
      between limb development and the urogenital system had been established with the
      evolution of the earliest terrestrial tetrapods. Importantly, many lizard species
      with genetic sex determination, including the ones we studied, are oviparous and
      may represent valuable animal models for experimental tests of the association
      between prenatal exposure to androgens or estrogens and digit ratios.

PMID- 16604564
TI  - Risk of invasive breast carcinoma among women diagnosed with ductal carcinoma in
      situ and lobular carcinoma in situ, 1988-2001.
AB  - BACKGROUND: Incidence rates of ductal carcinoma in situ (DCIS) and lobular
      carcinoma in situ (LCIS) have been rising, but little is known about which
      patients will develop invasive breast cancer or what types of tumors these
      patients may develop. METHODS: By using Surveillance, Epidemiology and End
      Results (SEER) data, the authors evaluated how types of invasive breast cancers
      diagnosed among 37,692 DCIS and 4490 LCIS patients differed and how clinical
      characteristics influenced subsequent breast cancer risk. RESULTS: Among DCIS
      patients, incidence rates of ipsilateral and contralateral invasive breast cancer
      were 5.4/1000 person-years and 4.5/1000 person-years, respectively; and among
      LCIS patients, incidence rates were 7.3/1000 person-years and 5.2/1000 person
      years, respectively. LCIS patients were 5.3-fold more likely than DCIS patients
      to develop invasive lobular carcinomas. Women whose DCIS had comedo histologic
      features or was poorly differentiated had 1.4-fold and 2.0-fold elevations in
      ipsilateral invasive breast cancer risk. Furthermore, among DCIS patients, 20-49
      year-olds and black women and Hispanic white women had 1.6, 2.7, and 2.3-fold
      elevated risks of Stage III/IV breast cancer compared with 50-59 year-olds and
      non-Hispanic whites, respectively. CONCLUSIONS: Screening young DCIS patients
      more frequently and improving the follow-up care of blacks and Hispanic whites
      with DCIS may reduce their risk of advanced-stage breast cancer. In addition,
      LCIS may be a precursor rather than just an ambiguous risk factor for invasive
      breast cancer, and, therefore, localized treatment for LCIS may be warranted.
      Given that incidence rates of DCIS and LCIS have been rising, investigations of
      these tumors should be continued to better understand their etiology and
      appropriate clinical management.

PMID- 16604563
TI  - Assessment of health-related quality of life in children with cancer: consistency
      and agreement between parent and child reports.
AB  - BACKGROUND: In pediatric settings, measures of health-related quality of life
      (HRQL) are often obtained by proxy, especially from parents, but the correlation
      between parental report and patient report has not been clearly established. In
      the current study, the authors examined the agreement between child and parent
      reports of HRQL in children with cancer (both those receiving treatment and those
      off treatment) and healthy controls. METHODS: Two groups of children with cancer
      who differed with regard to treatment status (n = 199) and a group of healthy
      control children (n = 108) were assessed using a standardized measure of HRQL.
      Both children and parents reported on the child's HRQL using parallel forms of
      the Children's Health Questionnaire. RESULTS: Significant parent-child
      correlations were found for all 10 HRQL scales, and these correlations were
      higher in the cancer groups compared with controls. Parents in the cancer groups
      tended to underestimate the HRQL of their children compared with the child
      report, although there were no significant parent-child mean differences in the
      group of patients who were off treatment and only 2 significant differences in
      the group of children receiving treatment. In contrast, parents in the control
      group tended to overestimate the HRQL of their children, and the parent-child
      differences were found to be larger, achieving statistical significance on 8 of
      10 scales. CONCLUSIONS: Parents and children tend to report comparable child HRQL
      outcomes, and this is particularly true in oncology populations. In cases in
      which the child is either too young or too ill to provide a self-report, parent
      reported HRQL can be viewed as a reliable substitute.

PMID- 16604565
TI  - Improved survival and chemotherapy response among patients with AIDS-related non
      Hodgkin's lymphoma receiving highly active antiretroviral therapy.
AB  - Highly active antiretroviral therapy (HAART) became available in the US in 1996.
      Using the population-based cancer registry, we identified 233 patients with AIDS
      related systemic NHL diagnosed in San Diego or Orange County in 1994-1999, of
      whom 137 were diagnosed 1996-1999. We performed Kaplan-Meier analyses to compare
      survival between patients who received HAART at NHL diagnosis or thereafter
      versus untreated patients and Cox proportional hazard models for adjusted
      survival. We used logistic regression to determine if concomitant HAART changed
      the probability of complete response to chemotherapy and the Mann-Whitney U-test
      to compare the median number of chemotherapy cycles between patients who received
      HAART during chemotherapy versus those who did not. Among patients diagnosed with
      NHL in 1996-1999, 40 (29%) were taking HAART at NHL diagnosis. The median
      survival was three months among patients who did not receive HAART versus 16
      months among HAART-treated patients. HAART, chemotherapy, high performance
      status, and NHL stage < IV were associated with improved survival. Concomitant
      HAART, completion of > or = 6 chemotherapy cycles, and NHL stage < IV were
      associated with complete response to chemotherapy. The median number of
      chemotherapy cycles was five among patients who received HAART concomitant with
      chemotherapy versus three among untreated patients. We conclude that HAART should
      be initiated or continued after NHL diagnosis, including during the period of
      chemotherapy administration.

PMID- 16604566
TI  - The efficient direct synthesis of N,O-acetal compounds as key intermediates of
      discorhabdin A: oxidative fragmentation reaction of alpha-amino acids or beta
      amino alcohols by using hypervalent iodine(III) reagents.
AB  - Hypervalent iodine(III) reagents are readily available, easy to handle, and have
      a low toxicity and similar reactivities to those of heavy metal reagents, and
      hence they are used for various oxidative reactions. The oxidative cleavage of
      alkynes or carbonyl compounds by using bis(trifluoroacetoxy)iodo(III)
      pentafluorobenzene (C(6)F(5)I(OCOCF(3))(2)) has been reported. Herein, the
      efficient direct synthesis of N,O-acetal compounds as key intermediates of
      discorhabdin A, by the oxidative fragmentation reaction of alpha-amino acids or
      beta-amino alcohols by using C(6)F(5)I(OCOCF(3))(2), is described.

PMID- 16604567
TI  - Assembly of nanotubes of poly(4-vinylpyridine) and poly(acrylic acid) through
      hydrogen bonding.
AB  - Nanotubes of poly(4-vinylpyridine) (PVP) and poly(acrylic acid) (PAA) were
      fabricated by hydrogen bonding based on layer-by-layer (LbL) assembly. The
      uniform and flexible tubular structures were characterized by scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM). FTIR and X-ray
      photoelectron spectroscopy (XPS) measurements confirm the formation of hydrogen
      bonds in the assembled nanotubes. PAA can be released from the assembled PAA/PVP
      nanotubes in a basic aqueous solution to give the walls of the tubes a porous
      structure. Such assembled nanotubes can be considered as carriers for catalysts
      or drugs, especially in aqueous solution against capillary force.

PMID- 16604568
TI  - How high the spin? Allowed and forbidden spin states in transition-metal
      chemistry.

PMID- 16604570
TI  - Highly diastereoselective silyl-modified sakurai multicomponent reaction.

PMID- 16604569
TI  - Surfactant-modulated switching of molecular transport in nanometer-sized pores of
      membrane gates.

PMID- 16604571
TI  - Electrode surface ratio optimization for thermal performance in 3-D
      dielectrophoretic single-cell traps.
AB  - We present a systematic numerical analysis of the thermal properties of
      dielectrophoretic single-cell traps. The influence of the thermal conductivity of
      the wall material is investigated, as well as the influence of the electrical
      conductivity of the liquid and the applied potential. We also explore the effect
      of the electrode geometry on the thermal properties of the trap. We show that
      substrates with thermal conductivities smaller than 100 W/mK can affect
      significantly the temperature increase inside the traps. Our results also show,
      for the first time, that for flat electrodes there is an optimum electrode to
      trap surface area ratio for which the ratio of temperature increase in the liquid
      to dielectrophoretic force on a particle can be minimized. This result will be
      useful in the future development of optimized dielectrophoretic traps.

PMID- 16604572
TI  - Enhancement of the StreptoTag method for isolation of endogenously expressed
      proteins with complex RNA binding targets.
AB  - StreptoTag is a novel affinity chromatography-based method for the isolation of
      high- and low-affinity RNA binding proteins. Originally it was shown possible to
      isolate recombinant protein from yeast or bacterial extracts using small,
      specific, well-characterised RNA binding targets. Here we show that using an
      enhanced aptamer it is not only possible to efficiently immobilise large, highly
      structured RNA binding targets onto the streptomycin columns but also that the
      StreptoTag method can be used for the isolation and purification of endogenously
      expressed regulatory proteins, with relatively low abundance, from eukaryotic
      extracts. As an example for this we uncover the identity of a karyophilic
      cellular protein which specifically binds to an area within the large, highly
      folded structure that characterises the mRNA from the unique 3' region (U3) of
      the mouse mammary tumour virus (MMTV) long terminal repeat (LTR). Hence, this
      method is now suitable for the quick and efficient isolation and identification
      of novel RNA binding proteins such as regulatory factors.

PMID- 16604573
TI  - Radical cation formation in characterization of novel C3-symmetric disks and
      their precursors by matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry.
AB  - Four C3-symmetrical tris(dipeptide) disks and their precursors were characterized
      using matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI TOF MS). The C3-symmetrical disks were based on a benzene
      1,3,5-triscarboxamide core extended by oligopeptides with trialkoxyanilide tails.
      The results indicate that MALDI TOF MS is a powerful and straightforward
      analytical technique for characterizing C3-symmetrical disks and their
      precursors. Clear (pseudo)-molecular ion peaks could readily be identified. It is
      remarkable that strong radical ion signals were observed for all the compounds,
      including the anilines that were expected to be protonated prior to laser
      irradiation using acidic MALDI matrixes. Possible mechanisms for radical ion
      formation were investigated with the employment of radical scavengers, with
      various matrixes and with direct laser desorption/ionization (LDI). Most likely
      the radicals are formed by losing one electron from the aniline nitrogen and
      stabilized by conjugation through the phenyl ring. It appears that direct
      photo/thermal ionization of analytes is an important route for the radical ion
      formation of the compounds with trialkoxy aniline/anilide groups.

PMID- 16604574
TI  - Formal gas-phase polar [4 + 1+] cycloaddition of ionized methylene to alpha
      dicarbonyl compounds: synthesis of 2-unsubstituted 1,3-dioxoles.
AB  - Ion/molecule reactions of +CH2OCH2. with alpha-dicarbonyl compounds were
      performed via pentaquadrupole mass spectrometry. Besides the previously known [3+
      + 2] 1,3-cycloaddition reaction that forms cyclic 1,3-dioxonium ions, an
      unprecedented reaction proceeding formally by [4 + 1+] cycloaddition of ionized
      methylene (CH2+.) to the alpha-dicarbonyl compounds occurs competitively, leading
      to the gas-phase synthesis of several ionized 2-unsubstituted 1,3-dioxoles. This
      novel cycloaddition reaction may therefore be added to the set of methods
      available for the synthesis of 1,3-dioxoles.

PMID- 16604575
TI  - Bench partners.

PMID- 16604576
TI  - What's holding you back?

PMID- 16604577
TI  - The effects of the Roche AMPLICOR HIV-1 MONITOR UltraSensitive Test versions 1.0
      and 1.5 viral load assays and plasma collection tube type on determination of
      response to antiretroviral therapy and the inappropriateness of cross-study
      comparisons.
AB  - BACKGROUND: Because there are limited head-to-head data comparing antiretroviral
      combinations, physicians are tempted to rely on cross-trial comparisons to
      evaluate the relative efficacy of HIV drugs. However, a variety of factors can
      confound these comparisons, resulting in misleading or invalid conclusions.
      OBJECTIVES: To compare and evaluate the use of: (i) versions 1.0 and 1.5 of the
      Roche AMPLICOR HIV-1 MONITOR UltraSensitive assay, and (ii)
      ethylenediaminetetraacetic acid (EDTA) and plasma preparation (PPT) tubes on the
      proportion of HIV-infected patients who would be classified as virological
      responders in a multinational clinical trial. STUDY DESIGN: The study utilized
      was a randomized, double-blind trial comparing the efficacy and safety of
      atazanavir with efavirenz, each in combination with fixed-dose
      zidovudine/lamivudine, in antiretroviral-naive patients. To evaluate the effect
      of monitor kit version, paired plasma samples from 634 patients at week 48 were
      analyzed using both versions 1.0 and 1.5 of the monitor kit. To evaluate the
      effect of collection tube type, paired plasma samples collected from 584 patients
      at week 52 using both EDTA and PPT tubes were assayed. Patients were classified
      as responders if HIV-1 RNA levels were below a pre-determined level of
      quantification (LOQ), both 400 and 50 copies/ml. RESULTS AND CONCLUSIONS:
      Substantially higher HIV-1 RNA levels were observed with monitor kit version 1.5,
      resulting in lower response rates. The version 1.0 monitor kit resulted in a 7%
      increase in patients classified as responders at the LOQ of 400 copies/ml and a
      13% increase at the LOQ of 50 copies/ml. Consistently higher response rates (11%
      higher at the LOQ of 400 copies/ml and 34% higher at the LOQ of 50 copies/ml)
      were also observed when samples were collected in EDTA tubes compared with PPT
      tubes. Differences in monitor kit sensitivity and plasma collection procedures
      are key factors in study results and suggest caution when performing cross-study
      comparisons.

PMID- 16604578
TI  - Comments on "can stress cause depression?" b H.M. van Praag. Progress in Neuro
      psychopharmacology and Biological Psychiatry 28, 2004, 891-907.

PMID- 16604580
TI  - Evaluating education effectiveness.

PMID- 16604579
TI  - Development of biological filter as tertiary treatment for effective nitrogen
      removal: Biological filter for tertiary treatment.
AB  - A biological filtration process applicable to tertiary treatment of sewage for
      effective nitrogen removal was developed. It consisted of a nitrification filter
      (Filter 1) and/or a polishing filter with anoxic and oxic parts (Filter 2). A
      pilot plant set at a municipal sewage treatment plant was operated for 525 d with
      feed of real sewage. The maximum apparent nitrification rate in Filter 1 in
      winter was 0.54 kg N/m3- filter-bed d. In Filter 2, the maximum denitrification
      capacity was 4 kg N/m3 filter-bed d) in winter. SS was stably removed and high
      transparency water was obtained. The target water quality (SS, BOD, and T-N5
      mg/L) was accomplished in winter with the LV of 202 m/d in Filter 2, which
      corresponds to 0.24 h of HRT. These results proved that this process is compact,
      stable, convenient to install, and cost effective to build and operate as
      tertiary treatment to remove nitrogen effectively.

PMID- 16604581
TI  - Lymphocytes: not useless after all.
AB  - Half a century ago, an immunologist named N. Avrion Mitchison showed that
      lymphocytes--then thought to be useless--triggered tumor rejection in mice.

PMID- 16604582
TI  - Prostate stem cell antigen (PSCA) expression in human prostate cancer tissues:
      implications for prostate carcinogenesis and progression of prostate cancer.

PMID- 16604583
TI  - Getting teams to talk: learning to improve OR communications.

PMID- 16604584
TI  - Characteristics of high-energy neutrons estimated using the radioactive
      spallation products of Au at the 500-MeV neutron irradiation facility of KENS.
AB  - We carried out a shielding experiment of high-energy neutrons, generated from a
      tungsten target bombarded with primary 500-MeV protons at KENS, which penetrated
      through a concrete shield in the zero-degree direction. We propose a new method
      to evaluate the spectra of high-energy neutrons ranging from 8 to 500 MeV. Au
      foils were set in a concrete shield, and the reaction rates for 13 radionuclides
      produced by the spallation reactions on the Au targets were measured by
      radiochemical techniques. The experimental results were compared with those
      obtained by the MARS14 Monte-Carlo code. A good agreement (between them) was
      found for energies beyond 100 MeV. The profile of the neutron spectrum, ranging
      from 8 to 500 MeV, does not depend on the thickness of the concrete shield.

PMID- 16604585
TI  - Benchmark studies of induced radioactivity produced in LHC materials, Part I:
      Specific activities.
AB  - Samples of materials which will be used in the LHC machine for shielding and
      construction components were irradiated in the stray radiation field of the CERN
      EU high-energy reference field facility. After irradiation, the specific
      activities induced in the various samples were analysed with a high-precision
      gamma spectrometer at various cooling times, allowing identification of isotopes
      with a wide range of half-lives. Furthermore, the irradiation experiment was
      simulated in detail with the FLUKA Monte Carlo code. A comparison of measured and
      calculated specific activities shows good agreement, supporting the use of FLUKA
      for estimating the level of induced activity in the LHC.

PMID- 16604586
TI  - Benchmark studies of induced radioactivity produced in LHC materials, Part II:
      Remanent dose rates.
AB  - A new method to estimate remanent dose rates, to be used with the Monte Carlo
      code FLUKA, was benchmarked against measurements from an experiment that was
      performed at the CERN-EU high-energy reference field facility. An extensive
      collection of samples of different materials were placed downstream of, and
      laterally to, a copper target, intercepting a positively charged mixed hadron
      beam with a momentum of 120 GeV c(-1). Emphasis was put on the reduction of
      uncertainties by taking measures such as careful monitoring of the irradiation
      parameters, using different instruments to measure dose rates, adopting detailed
      elemental analyses of the irradiated materials and making detailed simulations of
      the irradiation experiment. The measured and calculated dose rates are in good
      agreement.

PMID- 16604587
TI  - Induced radioactivity in the forward shielding and semiconductor tracker of the
      ATLAS detector.
AB  - The radioactivity induced in the forward shielding, copper collimator and
      semiconductor tracker modules of the ATLAS detector has been studied. The ATLAS
      detector is a long-term experiment which, during operation, will require to have
      service and access to all of its parts and components. The radioactivity induced
      in the forward shielding was calculated by Monte Carlo methods based on GEANT3
      software tool. The results show that the equivalent dose rates on the outer
      surface of the forward shielding are very low (at most 0.038 microSv h(-1)). On
      the other hand, the equivalent dose rates are significantly higher on the inner
      surface of the forward shielding (up to 661 microSv h(-1)) and, especially, at
      the copper collimator close to the beampipe (up to 60 mSv h(-1)). The
      radioactivity induced in the semiconductor tracker modules was studied
      experimentally. The module was activated by neutrons in a training nuclear
      reactor and the delayed gamma ray spectra were measured. From these measurements,
      the equivalent dose rate on the surface of the semiconductor tracker module was
      estimated to be < 100 microSv h(-1) after 100 d of Large Hadron Collider (LHC)
      operation and 10 d of cooling.

PMID- 16604588
TI  - Development of a connection-method calculation utility for the DORT-TORT code.
AB  - A code package has been developed to utilise connection-method calculation for
      both 2-D and 3-D SN codes, DORT-TORT, extending further the capabilities of
      DORSET/TORSET. It also includes support utilities to make input preparation
      easier. Potential uses of the method are, for example, to allow the coupling of
      one problem to the end of another by transforming output fluxes of the former
      into an external source term for the latter. For evaluating the code's
      applicability in a more specific way, the coupling calculation has been performed
      using a two-leg duct-streaming problem with a 14 MeV neutron source. The RZ-RZ
      (DORT) result shows good overall agreement with the reference MCNP4B result.
      However, it is also found that the result is influenced by the dimension of the
      calculation region and that some transformation error has occurred. For
      evaluating the 3-D transformation, full preparation of first collision source is
      required for TORT.

PMID- 16604589
TI  - Radioactivity evaluation for the KSTAR tokamak.
AB  - The deuterium-deuterium (D-D) reaction in the KSTAR (Korea Superconducting
      Tokamak Advanced Research) tokamak generates neutrons with a peak yield of 2.5 x
      10(16) s(-1) through a pulse operation of 300 s. Since the structure material of
      the tokamak is irradiated with neutrons, this environment will restrict work
      around and inside the tokamak from a radiation protection physics point of view
      after shutdown. Identification of neutron-produced radionuclides and evaluation
      of absorbed dose in the structure material are needed to develop a guiding
      principle for radiation protection. The activation level was evaluated by MCNP4C2
      and an inventory code, FISPACT. The absorbed dose in the working area decreased
      by 4.26 x 10(-4) mrem h(-1) in the inner vessel 1.5 d after shutdown.
      Furthermore, tritium strongly contributes to the contamination in the graphite
      tile. The amount of tritium produced by neutrons was 3.03 x 10(6) Bq kg(-1) in
      the carbon graphite of a plasma-facing wall.

PMID- 16604590
TI  - Shielding design of the ITER NBI duct for nuclear and bremsstrahlung radiation.
AB  - Three-dimensional Monte Carlo shielding analyses are conducted on the ITER
      Neutral Beam Injection (NBI) duct for the nuclear and bremsstrahlung radiation.
      The detailed distribution is evaluated about the nuclear heating rate and surface
      heat load of the NBI duct wall by the neutron and photon transport calculation.
      The analytical representations of these nuclear responses are established as a
      function of the distance from the blanket surface. It is clarified that these
      representations are different between the duct wall facing the plasma and that
      hidden from the plasma, and also between the duct wall in the blanket region and
      that in the vacuum vessel region. These results are very useful for the shielding
      design of the NBI duct wall in the nuclear fusion reactor.

PMID- 16604591
TI  - Neutron and photon shielding benchmark calculations by MCNP on the LR-0
      experimental facility.
AB  - In the framework of the REDOS project, the space-energy distribution of the
      neutron and photon flux has been calculated over the pressure vessel simulator
      thickness of the LR-0 experimental reactor, Rez, Czech Republic. The results
      calculated by the Monte Carlo code MCNP4C are compared with the measurements
      performed in the Nuclear Research Institute, Rez. The spectra have been measured
      at the barrel, in front of, inside and behind the pressure vessel in different
      configurations. The neutron measurements were performed in the energy range 0.1
      10 MeV. This work has been done in the frame of the 5th Frame Work Programme of
      the European Community 1998-2002.

PMID- 16604592
TI  - Calculation with MCNP of capture photon flux in VVER-1000 experimental reactor.
AB  - The aim of this study is to obtain by Monte Carlo method the high energy photon
      flux due to neutron capture in the internals and vessel layers of the
      experimental reactor LR-0 located in REZ, Czech Republic, and loaded with VVER
      1000 fuel. The calclated neutron, photon and photon to neutron flux ratio are
      compared with experimental measurements performed with a multi-parameter stilbene
      detector. The results show clear underestimation of photon flux in downcomer and
      some overestimation at vessel surface and 1/4 thickness but a good fitting for
      deeper points in vessel.

PMID- 16604593
TI  - Multiple solar particle event dose time profile predictions using Bayesian
      inference.
AB  - The prediction of solar particle event occurrence and the resulting effects on
      humans and electronics continues to be a mission and/or life-threatening concern
      for the National Aeronautics and Space Administration and military and commercial
      satellite operators. While the frequency of events generally follows the solar
      cycle, individual event occurrence is sporadic and the prediction of resulting
      effects prior to the event onset is difficult. In one approach to space weather
      prediction, the forecaster begins to make predictions after the onset of an
      event. Previous work proved the efficacy of a forecasting methodology that used
      Bayesian inference and dose and/or dose rate information obtained early after the
      onset of an event to make predictions of dose and dose rate time profiles out to
      120 h beyond onset. The previous work, however, was restricted to predictions for
      single-event solar particle events. Some of the largest recorded events,
      including the October 1989 and August 1972 events, were actually multiple events.
      In this study, we present an analysis of nine large events, some single and some
      multiple. This work ties together particle flux and fluence data with dose rate
      and dose calculations in an effort to develop a criterion for characterising an
      event as multiple and thus, generalising the Bayesian methodology to allow
      predictions for all events. Dose time profile predictions are made for the four
      separate events that made up the October 1989 event.

PMID- 16604594
TI  - Benchmarking of MCNPX with the experimental measurements of high-energy helium
      ions in HIMAC facility.
AB  - The main aim of this study is the qualfication of MCNPX code by using the
      experimental information obtained at HIMAC facility on the bombardment of
      different materials with He ions accelerated to 100 and 180 MeV/nucleon. The flux
      of secondary neutrons at different angles relative to ion direction is calculated
      and compared with published experimental data. Main findings are the reasonable
      modelling of the high-energy part of the secondary neutrons at forward angles and
      the code fail for the low-energy part.

PMID- 16604595
TI  - Comparison of high-energy trapped particle environments at the Earth and Jupiter.
AB  - The 'Van Allen belts' of the trapped energetic particles in the Earth's
      magnetosphere were discovered by the Explorer I satellite in 1958. In addition,
      in 1959, it was observed that UHF radio emissions from Jupiter probably had a
      similar source--the Jovian radiation belts. In this paper, the global
      characteristics of these two planets' trapped radiation environments and
      respective magnetospheres are compared and state-of-the-art models used to
      generate estimates of the high-energy electron (> or = 100 keV) and proton (> or
      = 1 MeV) populations--the dominant radiation particles in these environments. The
      models used are the AP8/AE8 series for the Earth and the Divine-Garrett/GIRE
      model for Jupiter. To illustrate the relative magnitude of radiation effects at
      each planet, radiation transport calculations were performed to compute the total
      ionising dose levels at the geosynchronous orbit for the Earth and at Europa
      (Jupiter's 4th largest moon) for Jupiter. The results show that the dose rates
      are -0.1 krad(Si) d(-1) at the geosynchronous orbit and -30 krad(Si) d((-1) at
      Europa for a 2.5 mm spherical shell aluminium shield--a factor of -300 between
      the two planets.

PMID- 16604596
TI  - Simulation of germanium detector calibration using the Monte Carlo method:
      comparison between point and surface source models.
AB  - Simulation of detector calibration using the Monte Carlo method is very
      convenient. The computational calibration procedure using the MCNP code was
      validated by comparing results of the simulation with laboratory measurements.
      The standard source used for this validation was a disc-shaped filter where
      fission and activation products were deposited. Some discrepancies between the
      MCNP results and laboratory measurements were attributed to the point source
      model adopted. In this paper, the standard source has been simulated using both
      point and surface source models. Results from both models are compared with each
      other as well as with experimental measurements. Two variables, namely, the
      collimator diameter and detector-source distance have been considered in the
      comparison analysis. The disc model is seen to be a better model as expected.
      However, the point source model is good for large collimator diameter and also
      when the distance from detector to source increases, although for smaller sizes
      of the collimator and lower distances a surface source model is necessary.

PMID- 16604597
TI  - A new low-energy bremsstrahlung generator for GEANT4.
AB  - The 2BN bremsstrahlung cross section is a well-adapted distribution to describe
      the radiative processes at low-electron kinetic energy (E(k) < 500 keV). In this
      work a method to implement this distribution in a Monte Carlo generator is
      developed.

PMID- 16604598
TI  - MCNP simulation of a Theratron 780 radiotherapy unit.
AB  - A Theratron 780 (MDS Nordion) 60Co radiotherapy unit has been simulated with the
      Monte Carlo code MCNP. The unit has been realistically modelled: the cylindrical
      source capsule and its housing, the rectangular collimator system, both the
      primary and secondary jaws and the air gaps between the components. Different
      collimator openings, ranging from 5 x 5 cm2 to 20 x 20 cm2 (narrow and broad
      beams) at a source-surface distance equal to 80 cm have been used during the
      study. In the present work, we have calculated spectra as a function of field
      size. A study of the variation of the electron contamination of the 60Co beam has
      also been performed.

PMID- 16604599
TI  - Monte Carlo estimation of the dose and heating of cobalt adjuster rods irradiated
      in the CANDU 6 reactor core.
AB  - The present work is a part of a more complex project related to the replacement
      of the original stainless steel adjuster rods with cobalt assemblies in the CANDU
      6 reactor core. The 60Co produced by 59Co irradiation could be used extensively
      in medicine and industry. The paper will mainly describe some of the reactor
      physics and safety requirements that must be carried into practice for the Co
      adjuster rods. The computations related to the neutronic equivalence of the
      stainless steel adjusters with the Co adjuster assemblies, as well as the
      estimations of the activity and heating of the irradiated cobalt rods, are
      performed using the Monte Carlo codes MCNP5 and MONTEBURNS 2.1. The activity
      values are used to evaluate the dose at the surface of the device designed to
      transport the cobalt adjusters.

PMID- 16604601
TI  - Characterisation of a neutron beam available at the RPI using a set of Bonner
      spheres.
AB  - The use of Bonner spheres to characterise radiation fields is abundantly
      documented in the literature. This study, carried out using the state-of-the-art
      Monte Carlo code MCNPX and the deconvolution program MAXED, aims to characterise
      the RPI epithermal neutron beam using of a set of Bonner spheres of different
      radii surrounding a 3He detector. The energy range of interest in this study
      covers from thermal to 10 MeV. This purely computational study aims to assess the
      feasibility of using the method previously mentioned to improve the knowledge of
      the energy and intensity characteristics of the epithermal beam.

PMID- 16604600
TI  - Calculation of the store house worker dose in a lost wax foundry using MCNP-4C.
AB  - Lost wax casting is an industrial process which permits the transmutation into
      metal of models made in wax. The wax model is covered with a silicaceous shell of
      the required thickness and once this shell is built the set is heated and wax
      melted. Liquid metal is then cast into the shell replacing the wax. When the
      metal is cool, the shell is broken away in order to recover the metallic piece.
      In this process zircon sands are used for the preparation of the silicaceous
      shell. These sands have varying concentrations of natural radionuclides: 238U,
      232Th and 235U together with their progenics. The zircon sand is distributed in
      bags of 50 kg, and 30 bags are on a pallet, weighing 1,500 kg. The pallets with
      the bags have dimensions 80 cm x 120 cm x 80 cm, and constitute the radiation
      source in this case. The only pathway of exposure to workers in the store house
      is external radiation. In this case there is no dust because the bags are closed
      and covered by plastic, the store house has a good ventilation rate and so radon
      accumulation is not possible. The workers do not touch with their hands the bags
      and consequently skin contamination will not take place. In this study all
      situations of external irradiation to the workers have been considered;
      transportation of the pallets from vehicle to store house, lifting the pallets to
      the shelf, resting of the stock on the shelf, getting down the pallets, and
      carrying the pallets to production area. Using MCNP-4C exposure situations have
      been simulated, considering that the source has a homogeneous composition, the
      minimum stock in the store house is constituted by 7 pallets, and the several
      distances between pallets and workers when they are at work. The photons flux
      obtained by MCNP-4C is multiplied by the conversion factor of Flux to Kerma for
      air by conversion factor to Effective Dose by Kerma unit, and by the number of
      emitted photons. Those conversion factors are obtained of ICRP 74 table 1 and
      table 17 respectively. This is the way to obtain a function giving dose rate
      around the source.

PMID- 16604602
TI  - Efficient heterogeneous execution of Monte Carlo shielding calculations on a
      Beowulf cluster.
AB  - Recent work has been done in using a high-performance 'Beowulf' cluster computer
      system for the efficient distribution of Monte Carlo shielding calculations. This
      has enabled the rapid solution of complex shielding problems at low cost and with
      greater modularity and scalability than traditional platforms. The work has shown
      that a simple approach to distributing the workload is as efficient as using more
      traditional techniques such as PVM (Parallel Virtual Machine). In addition, when
      used in an operational setting this technique is fairer with the use of resources
      than traditional methods, in that it does not tie up a single computing resource
      but instead shares the capacity with other tasks. These developments in computing
      technology have enabled shielding problems to be solved that would have taken an
      unacceptably long time to run on traditional platforms. This paper discusses the
      BNFL Beowulf cluster and a number of tests that have recently been run to
      demonstrate the efficiency of the asynchronous technique in running the MCBEND
      program. The BNFL Beowulf currently consists of 84 standard PCs running RedHat
      Linux. Current performance of the machine has been estimated to be between 40 and
      100 Gflop s(-1). When the whole system is employed on one problem up to four
      million particles can be tracked per second. There are plans to review its size
      in line with future business needs.

PMID- 16604603
TI  - Mars14 Monte Carlo simulation for the shielding studies of the J-PARC 3 GeV ring.
AB  - MARS14 Monte Carlo simulations were performed for collimation and shielding
      studies of the J-PARC 3 GeV synchrotron ring. The beam line module locations in
      the 348.3 m ring and the curved tunnel sections were described by the 'MAD-MARS
      beam line builder' tool. A 400 MeV proton beam loss distribution, calculated with
      the STRUCT code, was used as a 4 kW source term in the collimator region, with 1
      kW source terms in the injection and extraction regions at 400 MeV and 3 GeV,
      respectively. Deep penetration calculations were carried out with good statistics
      using a newly developed three-dimensional multi-layer technique. Prompt dose-rate
      distributions were calculated inside and outside the concrete and soil shield up
      to the ground level. Using the calculation results obtained thus, an effective
      shielding design was made.

PMID- 16604604
TI  - Shielding calculations for a 100 MeV 30 mA proton beam.
AB  - The Study and Production of Exotic Species (SPES) project employs a 100 MeV, 30
      mA proton beam that strikes a primary target. The resulting high-energy neutron
      flux impinges on a secondary target of depleted uranium to produce, through
      fission, beams of short-lived, neutron-rich nuclei. This paper deals with some of
      the preliminary shielding calculations for the bunker. Monte Carlo is employed
      with MCNPX and, because of the deep penetrations involved, the in-house variance
      reduction optimiser, the direct statistical approach. The calculations exhibited
      a number of typical features that are addressed and discussed.

PMID- 16604605
TI  - Radioprotection calculations for MEGAPIE.
AB  - The MEGAwatt PIlot Experiment (MEGAPIE) liquid lead-bismuth spallation neutron
      source will commence operation in 2006 at the SINQ facility of the Paul Scherrer
      Institut. Such an innovative system presents radioprotection concerns peculiar to
      a liquid spallation target. Several radioprotection issues have been addressed
      and studied by means of the Monte Carlo transport code, FLUKA. The dose rates in
      the room above the target, where personnel access may be needed at times, from
      the activated lead-bismuth and from the volatile species produced were
      calculated. Results indicate that the dose rate level is of the order of 40 mSv
      h(-1) 2 h after shutdown, but it can be reduced below the mSv h(-1) level with
      slight modifications to the shielding. Neutron spectra and dose rates from
      neutron transport, of interest for possible damage to radiation sensitive
      components, have also been calculated.

PMID- 16604606
TI  - Recent enhancements to the MARS15 code.
AB  - The MARS code is under continuous development and has recently undergone
      substantial improvements that further increase its reliability and predictive
      power in numerous shielding, accelerator, detector and space applications. The
      major developments and new features of the MARS15 (2004) version described in
      this paper concern an extended list of elementary particles and arbitrary heavy
      ions and their interaction cross sections, inclusive and exclusive nuclear event
      generators, module for modelling particle electromagnetic interactions, enhanced
      geometry and histogramming options, improved MAD-MARS Beam Line Builder, enhanced
      graphical user interface and an MPI-based parallelisation of the code.

PMID- 16604607
TI  - Towards a heavy-ion transport capability in the MARS15 code.
AB  - In order to meet the challenges of new accelerator and space projects and further
      improve modelling of radiation effects in microscopic objects, heavy-ion
      interaction and transport physics have been recently incorporated into the MARS15
      Monte Carlo code. A brief description of new modules is given in comparison with
      experimental data.

PMID- 16604608
TI  - MCNP5 for proton radiography.
AB  - The developmental version of MCNP5 has recently been extended to provide for
      continuous-energy transport of high-energy protons. This enhancement involves the
      incorporation of several significant new physics models into the code. Multiple
      Coulomb scattering is treated with an advanced model that takes account of
      projectile and nuclear target form factors. In the next version, this model will
      provide a coupled sampling of both angular deflection and collisional energy
      loss, including straggling. The proton elastic scattering model is also new,
      based on recent theoretical work. Charged particle transport in the presence of
      magnetic fields is accomplished either by using transfer maps from the COSY
      INFINITY code (in void regions) or by using an algorithm adapted from the MARS
      code (in void regions or in scattering materials). Work is underway to validate
      and implement the latest versions of the Cascade-Exciton Model and the Los Alamos
      Quark-Gluon String Model, which will process inelastic nuclear interactions and
      generate secondary particles.

PMID- 16604610
TI  - NASA Space Radiation Transport Code Development Consortium.
AB  - Recently, NASA established a consortium involving the University of Tennessee
      (lead institution), the University of Houston, Roanoke College and various
      government and national laboratories, to accelerate the development of a standard
      set of radiation transport computer codes for NASA human exploration
      applications. This effort involves further improvements of the Monte Carlo codes
      HETC and FLUKA and the deterministic code HZETRN, including developing nuclear
      reaction databases necessary to extend the Monte Carlo codes to carry out heavy
      ion transport, and extending HZETRN to three dimensions. The improved codes will
      be validated by comparing predictions with measured laboratory transport data,
      provided by an experimental measurements consortium, and measurements in the
      upper atmosphere on the balloon-borne Deep Space Test Bed (DSTB). In this paper,
      we present an overview of the consortium members and the current status and
      future plans of consortium efforts to meet the research goals and objectives of
      this extensive undertaking.

PMID- 16604609
TI  - The application of FLUKA to dosimetry and radiation therapy.
AB  - The FLUKA Monte Carlo code has been evolving over the last several decades and is
      now widely used for radiation shielding calculations. In order to facilitate the
      use of FLUKA in dosimetry and therapy applications, supporting software has been
      developed to allow the direct conversion of the output files from standard CT
      scans directly into a voxel geometry for transport within FLUKA. Since the CT
      scan information essentially contains only the electron density information over
      the scanned volume, one needs the specific compositions for each voxel
      individually. We present here the results of a simple algorithm to assign tissues
      in the human body to one of four categories: soft-tissue, hard-bone, trabecular
      bone and porous-lung. In addition, we explore the problem of the pathlength
      distributions in porous media such as trabecular bone. A mechanism will be
      implemented within FLUKA to allow for variable multipal fixed density materials
      to accommodate the pathlength distributions discovered.

PMID- 16604611
TI  - Shielding and fragmentation studies.
AB  - Radiation dosimetry for manned spaced missions depends on the ability to
      adequately describe the process of high-energy ion transport through many
      materials. Since the types of possible nuclear interactions are many and complex,
      transport models are used which depend upon a reliable source of experimental
      data. To expand the heavy ion database used in the models we have been measuring
      charge-changing cross sections and fragment production cross sections from heavy
      ion interactions in various elementa targets. These include materials flown on
      space missions such as carbon and aluminium, as well as those important in
      radiation dosimetry such as hydrogen, nitrogen and water. Measuring heavy-ion
      fragmentation through these targets also gives us the ability to determine the
      effectiveness of new materials proposed for shielding such as graphite composites
      and polyethylene hybrids. Measurement without a target present gives an
      indication of the level of contamination of the primary beam, which is also
      important in radiobiology experiments.

PMID- 16604612
TI  - Neutron production from 200-500 MeV proton interaction with spacecraft materials.
AB  - We report on detailed energy spectra of neutron production > 14 MeV from
      collisions of 200-500 MeV protons with combinations of aluminium, graphite and
      polyethylene. Comparisons of normalised neutron spectra are made with respect to
      incident proton energy, angle of neutron production and material. In general,
      carbon (graphite) or polyethylene (by itself or in combination with aluminium)
      reduce secondary neutron production > 14 MeV relative to the production from
      interactions in aluminium.

PMID- 16604613
TI  - SPE dose prediction using locally weighted regression.
AB  - When astronauts are outside Earth's protective magnetosphere, they are subject to
      large radiation doses resulting from solar particle events. The total dose
      received from a major solar particle event in deep space could cause severe
      radiation poisoning. The dose is usually received over a 20-40 h time interval
      but the event's effects may be reduced with an early warning system. This paper
      presents a method to predict the total dose early in the event. It uses a locally
      weighted regression model, which is easier to train, and provides predictions as
      accurate as the neural network models that were used previously.

PMID- 16604614
TI  - HETC radiation transport code development for cosmic ray shielding applications
      in space.
AB  - In order to facilitate three-dimensional analyses of space radiation shielding
      scenarios for future space missions, the Monte Carlo radiation transport code
      HETC is being extended to include transport of energetic heavy ions, such as are
      found in the galactic cosmic ray spectrum in space. Recently, an event generator
      capable of providing nuclear interaction data for use in HETC was developed and
      incorporated into the code. The event generator predicts the interaction product
      yields and production angles and energies using nuclear models and Monte Carlo
      techniques. Testing and validation of the extended transport code has begun. In
      this work, the current status of code modifications, which enable energetic heavy
      ions and their nuclear reaction products to be transported through thick
      shielding, are described. Also, initial results of code testing against available
      laboratory beam data for energetic heavy ions interacting in thick targets are
      presented.

PMID- 16604615
TI  - Overview of secondary neutron production relevant to shielding in space.
AB  - An overview of experimental secondary neutron measurements relevant to space
      related activities is presented. Stopping target yields and cross section
      measurements conducted at particle accelerators using heavy ions with energies >
      100 MeV per nucleon are discussed.

PMID- 16604616
TI  - The 12B counter: an active dosemeter for high-energy neutrons.
AB  - High-energy accelerators can produce strong time-structured radiation fields.
      Such dose shots are generated at linear machines with low duty cycles as well as
      at circular machines when complete fills are instantaneously lost. The main dose
      component behind thick shielding is due to high-energy neutrons occurring at that
      time structure. Dosemeters based on Geiger-Mueller tubes or proportional counters
      fail here completely. The 12B counter, a novel dosemeter made of a plastic
      scintillator using carbon activation for event-like exposure, has been
      introduced. High-energy neutrons activate the carbon nuclei by three inelastic
      reactions. The decay patterns with half-lives between 20 ms and 20 min can be
      exploited depending on the time structure of the radiation field. The response of
      the 12B counter was measured along with some other dosemeters, both active and
      passive, in the radiation field behind the lateral concrete shielding of a 7.5
      GeV proton transfer line.

PMID- 16604617
TI  - Developing instruments for measurement of plutonium activity in the environmental
      samples in the case of radiation accident.
AB  - According to the Russian norms, the permissible specific activity of 239Pu in the
      air and water are the lowest. Still the problem of low (compared to permissible)
      Pu activity measurement for environmental samples arises, for instance, in the
      case of radiation accident during transportation or storage of excess weapons
      grade plutonium transferred to the civil sphere of utilisation. The base method
      of Pu activity measurement is alpha spectrometry by using silicon detector. A new
      model of alpha spectrometer, based on silicon surface-barrier detector with
      background level less than 1-3 pulses per day has been developed. A simple
      unfolding method for the determination of Pu activity of samples with various
      thickness based on alpha spectrum measurement has been also developed. L-X photon
      detection is also used for reducing the measurement threshold of Pu activity
      determination. A method based on detecting L-X photons of Pu, excited by X rays
      and beta particles, is applied for further reducing the threshold.

PMID- 16604618
TI  - Energy and angular anisotropy optimisation of a p-type diode for in vivo
      dosimetry in photon-beam radiotherapy.
AB  - We present simulation work using the Monte Carlo code MCNPX that shows that there
      is a possibility of improving the silicon p-type diode as a radiation dosemeter,
      by altering the construction of the diode. Altering the diode die thickness can
      reduce the inherent angular anisotropy of the diode, with little effect on its
      energy response. Conversely, the contact material and geometry have a large
      impact on the energy response with little effect on the inherent angular
      anisotropy. By correct choice of contact material, the typical over-response -100
      keV relative to the response at 60Co energy can be reduced from approximately 20
      to 4. It is expected that further enhancements may be made with different
      geometries and materials.

PMID- 16604619
TI  - New method of voxel phantom creation: application for whole-body counting
      calibration and perspectives in individual internal dose assessment.
AB  - The purpose of this work is to present an innovative approach for the creation
      and application of voxel phantoms associated with the Monte Carlo calculation
      (MCNP) for the calibration of whole-body counting systems dedicated to the
      measurement of fission and activation products. The new method is based on a
      graphical user interface called 'OEDIPE' that allows to simulate a whole
      measurement process using all measurement parameters, the final goal being to
      approach a numerical calibration of the facilities. The creation of voxel
      phantoms and validation of the method are presented in this paper using the IGOR
      phantom. Finally, the efficiency of the method is discussed, in particular, with
      the perspective of validating IGOR as a suitable human-equivalent phantom and for
      the assessment of uncertainties in dose estimation due to the inhomogeneous
      distribution of activity in the body, correlated to the bio-kinetic behaviour of
      the radionuclides.

PMID- 16604620
TI  - Modelling of composite neutron scintillators.
AB  - Composite neutron scintillators consisting of neutron-insensitive fluorescent
      dopant particles (e.g. ZnS:Ag) embedded in a matrix material containing isotopes
      with high neutron cross sections that emit energetic charged particles (e.g. 6Li)
      are a popular method for neutron detection in a variety of applications. The size
      and volume doping fraction of the fluorescent dopant particles and the densities
      of both dopant particles and the matrix material determine the characteristics of
      the pulse-height spectrum of emitted light and the probability that capture of a
      neutron will result in scintillation. In this work, we characterise the effects
      of these parameters for ZnS:Ag particles in a lithiated glass matrix using a
      Monte Carlo simulation of composite neutron detectors that we have constructed.

PMID- 16604621
TI  - Characterisation of ionisation chambers for a mixed radiation field and
      investigation of their suitability as radiation monitors for the LHC.
AB  - Monitoring of the radiation environment is one of the key tasks in operating a
      high-energy accelerator such as the Large Hadron Collider (LHC). The radiation
      fields consist of neutrons, charged hadrons as well as photons and electrons with
      energy spectra extending from those of thermal neutrons up to several hundreds of
      GeV. The requirements for measuring the dose equivalent in such a field are
      different from standard uses and it is thus necessary to investigate the response
      of monitoring devices thoroughly before the implementation of a monitoring system
      can be conducted. For the LHC, it is currently foreseen to install argon- and
      hydrogen-filled high-pressure ionisation chambers as radiation monitors of mixed
      fields. So far their response to these fields was poorly understood and,
      therefore, further investigation was necessary to prove that they can serve their
      function well enough. In this study, ionisation chambers of type IG5 (Centronic
      Ltd) were characterised by simulating their response functions by means of
      detailed FLUKA calculations as well as by calibration measurements for photons
      and neutrons at fixed energies. The latter results were used to obtain a better
      understanding and validation of the FLUKA simulations. Tests were also conducted
      at the CERF facility at CERN in order to compare the results with simulations of
      the response in a mixed radiation field. It is demonstrated that these detectors
      can be characterised sufficiently enough to serve their function as radiation
      monitors for the LHC.

PMID- 16604622
TI  - Measurements of the response functions of a large size NE213 organic liquid
      scintillator for neutrons up to 800 MeV.
AB  - The response functions of 25.4 cm (length) x 25.4 cm (diameter) NE213 organic
      liquid scintillator have been measured for neutrons in the energy range from 20
      to 800 MeV at the Heavy-Ion Medical Accelerator in Chiba (HIMAC) and at the
      Research Center for Nuclear Physics (RCNP) of Osaka University. At HIMAC, white
      (continuous) energy spectrum neutrons were produced by the 400 MeV per nucleon
      carbon ion bombardment on a thick graphite target, whose energy spectrum has
      already been measured by Kurosawa et al., [Nucl. Sci. Eng. 132, 30 (1999)] and
      the response functions of the time-of-flight-gated monoenergetic neutrons in a
      wide energy range from 20 to 800 MeV were simultaneously measured. At RCNP, the
      quasi-monoenergetic neutrons were produced via 7Li(p,n)7Be reaction by 250 MeV
      proton beam bombardment on a thin 7Li target, and the TOF-gated 245 MeV peak
      neutrons were measured. The absolute peak neutron yield was obtained by the
      measurement of 478 keV gamma rays from the 7Be nuclei produced in a Li target.
      The measured results show that the response functions for monoenergetic neutrons
      < 250 MeV have a recoil proton plateau and an edge around the maximum light
      output, which increases with increasing incident neutron energy, on the other
      hand > 250 MeV, the plateau and the edge become unclear because the proton range
      becomes longer than the detector size and the escaping protons increase. It can
      be found that the efficiency of the 24.5 cm (diameter) x 25.4 cm (length) NE213
      for the 250 MeV neutrons is -10 times larger than the 12.7 cm (length) x 12.7 cm
      (diameter) NE213, which is widely used as a neutron spectrometer.

PMID- 16604623
TI  - Performance of a neutron spectrometer based on a PIN diode.
AB  - The neutron spectrometer discussed in this work consists of a PIN diode coupled
      with a polyethylene converter. Neutrons are detected through the energy deposited
      by recoil-protons in silicon. The maximum detectable energy is -6 MeV and is
      imposed by the thickness of the fully depleted layer (300 microm for the present
      device). The minimum detectable energy which can be assessed with pulse-shape
      discrimination (PSD) is -0.9 MeV. PSD is performed with a crossover method and
      setting the diode in the 'reverse-injection' configuration (i.e. with the N+
      layer adjacent to the converter). This configuration provides longer collection
      times for the electron-hole pairs generated by the recoil-protons. The limited
      interval of detectable energies restricts the application of this spectrometer to
      low-energy neutron fields, such as the ones which can be produced at facilities
      hosting low-energy ion accelerators. The capacity to reproduce continuous neutron
      spectra was investigated by optimising the electronic chain for pulse-shape
      discrimination. In particular, the spectrometer was irradiated with neutrons that
      were generated by striking a thick beryllium target with protons of several
      energies and the measured spectra were compared with data taken from the
      literature.

PMID- 16604624
TI  - Simulations of the mean chord length of a multi-element TEPC irradiated by
      monoenergetic neutrons.
AB  - In recent years IRSN has developed tissue-equivalent proportional counters
      (TEPCs) for neutron monitoring. A detector with a multi-element geometry was
      studied for personal dosimetry purposes. The determination of the personal dose
      equivalent using a multi-element TEPC requires to calculate the mean chord length
      of the charged particles in the counter gas. This paper presents the results of
      the simulations using the MCNPX code and explains the influence of the gas
      parameters on the mean chord length and the consequences on the dose equivalent
      response.

PMID- 16604625
TI  - Dose calculation system for remotely supporting radiotherapy.
AB  - The dose calculation system IMAGINE is being developed keeping in mind remotely
      supporting external radiation therapy using photon beams. The system is expected
      to provide an accurate picture of the dose distribution in a patient body, using
      a Monte Carlo calculation that employs precise models of the patient body and
      irradiation head. The dose calculation will be performed utilising super-parallel
      computing at the dose calculation centre, which is equipped with the ITBL
      computer, and the calculated results will be transferred through a network. The
      system is intended to support the quality assurance of current, widely carried
      out radiotherapy and, further, to promote the prevalence of advanced
      radiotherapy. Prototypes of the modules constituting the system have already been
      constructed and used to obtain basic data that are necessary in order to decide
      on the concrete design of the system. The final system will be completed in 2007.

PMID- 16604626
TI  - Development of a simple method to evaluate medical staff radiation dose and its
      application to a software system supporting PET facility operation.
AB  - In recent years, positron-emitting labelled radiopharmaceuticals have come to be
      used in conjunction with positron emission tomography (PET) in various clinical
      diagnoses. Radiation exposure of the medical staff is a key issue in the design
      of PET facilities intended to handle large numbers of persons for PET diagnosis.
      As a first step, the radiation dose to individuals who received
      radiopharmaceuticals was calculated using a mathematical phantom model and the
      EGS4 electromagnetic cascade Monte Carlo code and MCNP Monte Carlo code. Dose
      rate behind a lead shield was also calculated for various lead thicknesses. The
      radiation dose distribution around a syringe containing a positron emitter was
      calculated. The calculated dose distributions were fitted to polynomial
      equations. These calculations were evaluated against measurements. The second
      step was to evaluate medical staff dose at a specified time by superimposing dose
      distribution from each person who received radioisotopes taking into account
      radioactive decay. In this way, we developed software to support PET facility
      operation, namely, planning, prediction, control of medical staff dose and
      facility operation. This system was also designed to schedule daily
      radiopharmaceuticals production and to manage radioactive wastes by taking decay
      time into account.

PMID- 16604627
TI  - MINERVA: a multi-modality plugin-based radiation therapy treatment planning
      system.
AB  - Researchers at the INEEL, MSU, LLNL and UCD have undertaken development of
      MINERVA, a patient-centric, multi-modal, radiation treatment planning system,
      which can be used for planning and analysing several radiotherapy modalities,
      either singly or combined, using common treatment planning tools. It employs an
      integrated, lightweight plugin architecture to accommodate multi-modal treatment
      planning using standard interface components. The design also facilitates the
      future integration of improved planning technologies. The code is being developed
      with the Java programming language for interoperability. The MINERVA design
      includes the image processing, model definition and data analysis modules with a
      central module to coordinate communication and data transfer. Dose calculation is
      performed by source and transport plugin modules, which communicate either
      directly through the database or through MINERVA's openly published, extensible
      markup language (XML)-based application programmer's interface (API). All
      internal data are managed by a database management system and can be exported to
      other applications or new installations through the API data formats. A full
      computation path has been established for molecular-targeted radiotherapy
      treatment planning, with additional treatment modalities presently under
      development.

PMID- 16604629
TI  - Design tools for proton therapy nozzles based on the double-scattering foil
      technique.
AB  - Proton therapy has been increasing over the past several years, with several new
      treatment facilities being built in Europe, Japan and the United States. In this
      work, analytical and Monte Carlo tools were combined to model the passively
      scattered neurosurgery treatment beamline of the Harvard Cyclotron Laboratory
      (Cambridge, MA). The predicted three-dimensional dose distributions agree with
      actual measurements to within 0.1 mm for all quantities considered in central
      axis depth-dose curve and to within 2.1 mm for all quantities considered in the
      absorbed dose cross-field profile. The predicted neutron dose equivalent per
      therapeutic absorbed dose, H/D, was calculated at various locations representing
      clinically significant anatomical sites. Under typical treatment conditions, the
      average ratio of predicted-to-measured H/D is 1.8 in the gonadal region (50 cm
      from isocentre) and 3.4 in the thyroid region (21 cm from isocentre). The global
      ratio of predicted-to-measured H/D is 2.6.

PMID- 16604628
TI  - Clear-PEM: a dedicated PET camera for improved breast cancer detection.
AB  - Positron emission mammography (PEM) can offer a non-invasive method for the
      diagnosis of breast cancer. Metabolic images from PEM using 18F-fluoro-deoxy
      glucose, contain unique information not available from conventional morphologic
      imaging techniques like X-ray radiography. In this work, the concept of Clear
      PEM, the system presently developed in the frame of the Crystal Clear
      Collaboration at CERN, is described. Clear-PEM will be a dedicated scanner,
      offering better perspectives in terms of position resolution and detection
      sensitivity.

PMID- 16604631
TI  - A reassessment of Galileo radiation exposures in the Jupiter magnetosphere.
AB  - Earlier particle experiments in the 1970s on Pioneer-10 and -11 and Voyager-1 and
      -2 provided Jupiter flyby particle data, which were used by Divine and Garrett to
      develop the first Jupiter trapped radiation environment model. This model was
      used to establish a baseline radiation effects design limit for the Galileo
      onboard electronics. Recently, Garrett et al. have developed an updated Galileo
      Interim Radiation Environment (GIRE) model based on Galileo electron data. In
      this paper, we have used the GIRE model to reassess the computed radiation
      exposures and dose effects for Galileo. The 34-orbit 'as flown' Galileo
      trajectory data and the updated GIRE model were used to compute the electron and
      proton spectra for each of the 34 orbits. The total ionisation doses of electrons
      and protons have been computed based on a parametric shielding configuration, and
      these results are compared with previously published results.

PMID- 16604630
TI  - Absorbed dose rate estimation for protons, leptons and helium observed with AMS01
      experiment in low earth orbit during STS-91 mission.
AB  - The Alpha Magnetic Spectrometer (AMS01), a high-sensitivity particle
      spectrometer, was successfully flown for 10 d in June 1998 (STS91) in the orbit
      of the International Space Station (51.7 degrees, -380 km). A high-statistics
      dataset of galactic cosmic rays were measured as a function of geomagnetic
      latitude, including the primary protons, leptons and helium as well as the
      trapped and quasi-trapped proton and lepton components. In this paper, the
      absorbed dose rate owing to the protons, leptons and helium are presented and
      compared with measurements made by other instruments flown on the same mission.

PMID- 16604632
TI  - Modelling radiation loads to detectors in a SNAP mission.
AB  - In order to investigate the degradation of optical detectors of the Supernova
      Acceleration Project (SNAP) space mission because of irradiation, a three
      dimensional model of the satellite has been developed. A realistic radiation
      environment at the satellite orbit, including both galactic cosmic rays and
      cosmic ray trapped in radiation belts, has been taken into account. The modelling
      has been performed with the MARS14 Monte Carlo code. In a current design, the
      main contribution to dose accumulated in the photo-detectors is shown to be due
      to trapped protons. The contribution of primary alpha particles is estimated.
      Predicted performance degradation for the photodetector for a four-year space
      mission is 40% and this can be reduced further by means of shielding
      optimisation.

PMID- 16604633
TI  - Some recent measurements onboard spacecraft with passive detector.
AB  - Several passive detectors were used to estimate dosimetry and microdosimetry
      characteristics of radiation field onboard spacecraft, namely: thermoluminescent
      detectors (TLDs), mainly to appreciate the contribution of radiation with low
      linear energy transfer (LET); Si diode, to try to establish the contribution of
      fast neutrons; an LET spectrometer based on the chemically etched
      polyallyldiglycolcarbonate etched track detectors (PADC-TEDs). Detectors have
      been exposed onboard MIR and International Space Station (ISS) since 1997, they
      were also used during the MESSAGE 2 biological experiment, October 2003. The
      results are presented, analysed and discussed. Particular attention is devoted to
      the possibility of estimating neutron contribution based on data obtained with
      PADC-TED spectrometer of LET.

PMID- 16604634
TI  - SPE dose prediction using locally weighted regression.
AB  - When astronauts are outside earth's protective magnetosphere, they are subject to
      large radiation doses resulting from solar particle events (SPEs). The total dose
      received from a major SPE in deep space could cause severe radiation poisoning.
      The dose is usually received over a 20-40 h time interval but the event's effects
      may be mitigated with an early warning system. This paper presents a method to
      predict the total dose early in the event. It uses a locally weighted regression
      model, which is easier to train and provides predictions as accurate as neural
      network models previously used.

PMID- 16604635
TI  - Ford Motor Company NDE facility shielding design.
AB  - Ford Motor Company proposed the construction of a large non-destructive
      evaluation laboratory for radiography of automotive power train components. The
      authors were commissioned to design the shielding and to survey the completed
      facility for compliance with radiation doses for occupationally and non
      occupationally exposed personnel. The two X-ray sources are Varian Linatron 3000
      accelerators operating at 9-11 MV. One performs computed tomography of automotive
      transmissions, while the other does real-time radiography of operating engines
      and transmissions. The shield thickness for the primary barrier and all secondary
      barriers were determined by point-kernel techniques. Point-kernel techniques did
      not work well for skyshine calculations and locations where multiple sources
      (e.g. tube head leakage and various scatter fields) impacted doses. Shielding for
      these areas was determined using transport calculations. A number of MCNP
      [Briesmeister, J. F. MCNPCA general Monte Carlo N-particle transport code version
      4B. Los Alamos National Laboratory Manual (1997)] calculations focused on
      skyshine estimates and the office areas. Measurements on the operational facility
      confirmed the shielding calculations.

PMID- 16604636
TI  - Radiation safety impact for top-up operation at the NSRRC.
AB  - Radiation safety impact for the upcoming top-up operation at the National
      Synchrotron Radiation Research Center (NSRRC) has been investigated with emphasis
      on the consequence of injection efficiency. Keeping the storage ring at high
      stored current by frequent injections, the top-up operation will inevitably
      increase the radiation dose compared with that in the present decay mode,
      especially when the injection efficiency is low. In addition, significantly high
      level of radiation could stream through the ratchet wall openings during top-up
      injections while shutters are open. Therefore, a series of radiation safety
      analyses including calculations and measurements have been carried out to assess
      the feasibility of this mode on the prospective radiation protection. The paper
      summarises the evaluation and the corresponding action plans for radiation
      safety.

PMID- 16604637
TI  - Calculations of neutron shielding data for 10-100 MeV proton accelerators.
AB  - The characteristics of neutron sources and their attenuation in concrete were
      investigated in detail for protons with energies ranging from 10 to 100 MeV
      striking on target materials of C, N, Al, Fe, Cu and W. A two-step approach was
      adopted: thick-target double-differential neutron yields were first calculated
      from the (p, xn) cross sections recommended in the ICRU Report 63; further,
      transport simulations of those neutrons in concrete were performed by using the
      FLUKA Monte Carlo code. The purpose of this study is to provide reasonably
      accurate parameters for shielding design for 10-100 MeV proton accelerators.
      Source terms and the corresponding attenuation lengths in concrete for several
      target materials are given as a function of proton energies and neutron emission
      angles.

PMID- 16604638
TI  - Radiation streaming experiment through a labyrinth of the 12 GeV proton
      accelerator facility at KEK(2)--TLD REM-counter method.
AB  - The doses of radiation streaming through a labyrinth were measured using
      thermoluminescence dosemeters (TLDs) and neutron moderators for TLDs at the
      neutrino beam line of the 12 GeV proton accelerator facility of High Energy
      Accelerator Research Organization (KEK). The calculated doses using the Monte
      Carlo code, MCNPX basically agreed with the experimental results. However,
      unexpectedly, the calculated neutron doses were smaller than the measured ones
      along the upstream side of the labyrinth.

PMID- 16604640
TI  - Shielding design calculations for beam dump facility of KOMAC.
AB  - A project to construct the Korea Multi-purpose Accelerator Complex (KOMAC) is
      currently underway targeting a high-intensity proton beam with an average current
      of 4.8 mA. As for the first stage of construction, a 20 MeV linac is planned to
      be built by 2007 and additional DTL sections will be added to increase the proton
      energy to 100 MeV by 2012. In this paper, preliminary shielding estimates, such
      as the evaluation of the gamma ray and neutron dose rate around the beam dump,
      have been carried out with the three-dimensional (3-D) Monte Carlo transport code
      MCNPX in order to determine the shielding requirements. The tentative flux
      calculations using the 3-D deterministic code KATRIN, which can handle a coupled
      charged-neutral particle transport, were also performed and their results were
      compared with the MCNPX calculations.

PMID- 16604639
TI  - Shielding analysis at the upper section of the accelerator-driven system.
AB  - The proton beam duct of the accelerator-driven system (ADS) acts as a streaming
      path for spallation neutrons and photons and causes the activation of the magnets
      and other devices above the subcritical core. We have performed a streaming
      analysis at the upper section of the lead-bismuth target/cooled ADS (800 MWth).
      MCNPX was used to calculate the radiation dose from streamed neutrons and photons
      through the beam duct. For the secondary photon production calculation, cross
      sections for several actinides were substituted with plutonium because of the
      lack of gamma production cross section. From the results of this analysis, the
      neutron dose from the beam duct is seen to be about 20 orders higher than that of
      the bulk shield. The magnets and shield plug are heavily irradiated by streaming
      neutrons according to the DCHAIN-SP analysis.

PMID- 16604641
TI  - An improved photo-absorption cross section model for the physics models regime in
      MCNPX.
AB  - The photo-nuclear physics model capabilities utilising the CEM2k model
      implemented in the MCNPX code were improved > 100 MeV photon energy by basing the
      photon transport on experimental photo-absorption cross sections of nuclides
      rather than on free nucleon cross sections. Below 100 MeV, the photo-nuclear
      physics model now uses isotope-specific giant dipole resonance (GDR) photo
      absorption cross sections that are provided to the code in a parameterised form
      on a data file. Adjustments of the photo-fission cross sections were implemented
      to match the BOFOD evaluated data through a CEM2k internal parameter. The physics
      models with these improvements are better equipped to supplement the tabulated
      data based photo-nuclear MCNPX capability for isotopes with missing tabulated
      data evaluations especially in the GDR region, and has improved its predictive
      power at energies above the GDR resonances.

PMID- 16604643
TI  - Evaluation of induced radioactivity in structural material of Toshiba Training
      Reactor 'TTR1'.
AB  - A decommissioning programme for the Toshiba Training Reactor (TTR1), a swimming
      pool type reactor used for reactor physics experiments and material irradiation,
      was started in August 2001. As a part of the programme, induced radioactivity in
      structural material was evaluated using neutron flux data obtained with the three
      dimensional Sn code TORT. Induced activity was calculated with the isotope
      generation code ORIGEN-79 using activation cross section data created from multi
      group library based on JENDL-3. The obtained results for radioactivities such as
      60Co, 65Zn, 54Mn and 152Eu were compared with measured ones, and the present
      calculational method was confirmed to have enough accuracy.

PMID- 16604642
TI  - Modelling of activation processes for GR-280 graphite at Ignalina NPP.
AB  - Ignalina Nuclear Power Plant (INPP) operates two RBMK-1500 water-cooled graphite
      moderated channel-type power reactors. The total mass of graphite in the cores of
      both units at INPP is about 3600 tons. Modelling of activation processes in the
      reactor's structural materials is necessary for decommissioning planning, because
      large amounts of activated structural materials (graphite, stainless steel,
      concrete, etc.) should be managed as radioactive waste. Knowledge of radiological
      characteristics and a radioactive inventory of irradiated materials are essential
      in planning of the decommissioning processes. The purpose of this work was to
      perform conservative neutron activation analysis for decommissioning purposes of
      INPP. ORIGEN computer code was used for the calculations. Activity levels were
      calculated for different nuclides present in the graphite and estimates were made
      how these activity levels depend on irradiation time, neutron flux value and
      other parameters. Obtained results were compared with the data available from
      other investigations for GR-280 graphite.

PMID- 16604644
TI  - Activation calculations for the target of a spallation ultra-cold neutron source
      at PSI.
AB  - A spallation ultra-cold neutron source--UCN source--is scheduled to start
      operation at PSI in 2006 using up to 2 mA 590 MeV protons from the ring
      cyclotron. It will be operated in a pulsed mode with an average current of 20
      microA. For safe maintenance, during operation as well as handling, transport and
      storage of the UCN target assembly after its lifespan, detailed knowledge about
      the activation induced by the impinging protons and secondary radiation fields is
      required. The Monte Carlo transport code MCNPX was coupled with the European
      Activation System--EASY--to calculate the residual nuclide production in the UCN
      target assembly. The nuclide inventory is finally used to design the shielded
      exchange flask that is needed to safely remove and transport the UCN target
      assembly after its lifespan to a hotcell for dismantling.

PMID- 16604645
TI  - Comparison of thermal neutron distributions within shield materials obtained by
      experiments, SN and Monte Carlo code calculations.
AB  - Benchmark experiments of thermal neutron distributions within the shield
      materials, graphite pile and pure water, were performed by using 252Cf fission
      neutrons and gold foil activation detectors, and, to these results, the estimates
      obtained by using the discrete ordinate code ANISN and the Monte Carlo code MCNP5
      with two different cross-section libraries, ENDF/B-VI and the Japanese new
      version of JENDL-3.3, were compared. The results revealed that the MCNP5
      calculations with the two libraries closely agree with the experiments and that
      there are slight differences between the MCNP5 and the ANISN calculations. The
      differences are caused mainly by the overestimation of the thermal neutron
      absorption cross sections constructed in NJOY99. The ANISN calculations with the
      modified absorption cross sections reproduced the results of the MCNP5 fairly
      well.

PMID- 16604646
TI  - Activation analysis and first occupational dose rates estimates for the Laser
      Megajoule facility.
AB  - A three-dimensional neutronic modelling of the LMJ facility has been performed.
      The Monte Carlo transport code TRIPOLI is used to obtain the neutron spectra
      required for the inventory code FISPACT. Nodal activation responses and time
      dependent decay gamma spectra are produced and used as source terms for further
      treatment by TRIPOLI for a range of engineering and safety assessments. It is
      shown that three-dimensional neutronic and nodal activation can be performed in a
      convenient way and the results obtained by this procedure will serve as a data
      base for design and S&E analysis.

PMID- 16604647
TI  - On the theory and simulation of multiple Coulomb scattering of heavy-charged
      particles.
AB  - The Moliere theory of multiple Coulomb scattering is modified to take into
      account the difference between processes of scattering off atomic nuclei and
      electrons. A simple analytical expression for angular distribution of charged
      particles passing through a thick absorber is found. It does not assume any
      special form for a differential scattering cross section and has a wider range of
      applicability than a gaussian approximation. A well-known method to simulate
      multiple Coulomb scatterings is based on treating 'soft' and 'hard' collisions
      differently. An angular deflection in a large number of 'soft' collisions is
      sampled using the proposed distribution function, a small number of 'hard'
      collision are simulated directly. A boundary between 'hard' and 'soft' collisions
      is defined, providing a precise sampling of a scattering angle (1% level) and a
      small number of 'hard' collisions. A corresponding simulating module takes into
      account projectile and nucleus charged distributions and exact kinematics of a
      projectile-electron interaction.

PMID- 16604648
TI  - Parallelising the MARS15 code with MPI for shielding applications.
AB  - The MARS15 Monte Carlo code capabilities to deal with time-consuming deep
      penetration shielding problems and other computationally tough tasks in
      accelerator, detector and shielding applications, have been enhanced by a
      parallel processing option. It has been developed, implemented and tested on the
      Fermilab Accelerator Division Linux cluster and network of Sun workstations. The
      code uses a message passing interface MPI. It is scalable and demonstrates good
      performance. The general architecture of the code, specific uses of message
      passing and effects of a scheduling on the performance and fault tolerance are
      described.

PMID- 16604649
TI  - Simulation of secondary particle production and absorbed dose to tissue in light
      ion beams.
AB  - During radiation therapy with an ion beam, the production of secondary particles
      like neutrons, protons and heavier ions contribute to the dose delivered to
      tumour and healthy tissues outside the treated volume. Also, the secondary
      particles leaving the patient are of interest for radiation background around the
      ion-therapy facility. Calculations of secondary particle production and the dose
      absorbed by water, soft tissue and a multi-material phantom simulating the
      heterogeneous media of the patient body were performed for protons, helium,
      lithium and carbon ions in the energy range up to 400 MeV u(-1). The Monte Carlo
      code SHIELD-HIT for transport of protons and light ions in tissue-like media was
      used in these studies. The neutron ambient dose-equivalent, H*(10), was
      determined for neutrons leaving the water phantom irradiated with different light
      ion beams. The comparison of calculated secondary particle production in the
      water and PMMA phantoms irradiated with helium and carbon ions shows satisfactory
      agreement with experimental data.

PMID- 16604650
TI  - Magnetic field tracking with MCNP5.
AB  - With the introduction of continuous-energy heavy charged particle transport in
      MCNP5, the need for tracking charged particles in a magnetic field becomes
      increasingly important. Two methods for including magnetic field effects on
      charged particles are included in the proton transport version of the code. The
      first technique utilises transfer maps produced by the beam dynamics simulation
      and analysis code COSY INFINITY. This method is fast and accurate; however, its
      use is limited to void cells only and to ensembles of particles with a fairly
      small energy spread. The second technique, particle ray tracing, is based on an
      algorithm adopted from the MARS transport code. This method can be applied to
      both void and material cells and is valid over a very large range of particle
      energies. Results from tracking particles in a quadrupole 'identity lens' using
      the two techniques are compared.

PMID- 16604651
TI  - Radiation exposure measurement onboard civil aircraft.
AB  - The active dosemeter DOSTEL based on two silicon planar detectors was flown on
      civil aircraft flights to study the radiation exposure of air crew members. The
      altitude and latitude dependence of count and dose rates as well as long-term
      variations are measured. After calibration of the DOSTEL response against
      measurements of a TEPC instrument, total dose-equivalent values for various
      flights are compared with H*(10) calculations by EPCARD yielding a ratio of 1.02
      +/- 0.09 (standard variation).

PMID- 16604652
TI  - Aircrew dosimetry by means of experimental measurements and calculations: results
      obtained during the year 2003.
AB  - The results of measurements performed during the year 2003 onboard aircraft,
      mostly during regular commercial flights of the Czech Airlines (CSA) are
      presented. The studies were performed during more than 30 individual flights,
      several dosemeters and equipments were used for both neutron and non-neutron
      components of the onboard radiation field. CSA colleagues submitted us for all
      flights with navigation data necessary for the calculation of onboard aircraft
      crew exposure with transport codes EPCARD and CARI. Direct readings of
      experimental equipments were corrected on the base of the calibration in CERN
      high-energy radiation fields. A reasonable agreement of measured and calculated
      data was observed. During one of the flights, a very deep Forbush decrease
      occurred. The experimental results confronted with calculation permitted to
      obtain new view on the influence of such events on aircraft crew exposure.

PMID- 16604653
TI  - Aircrew dosimetry using the Predictive Code for Aircrew Radiation Exposure
      (PCAIRE).
AB  - During 2003, a portable instrument suite was used to conduct cosmic radiation
      measurements on 49 jet-altitude flights, which brings the total number of in
      flight measurements by this research group to over 160 flights since 1999. From
      previous measurements, correlations have been developed to allow for the
      interpolation of the dose-equivalent rate for any global position, altitude and
      date. The result was a Predictive Code for Aircrew Radiation Exposure (PCAIRE),
      which has since been improved. This version of the PCAIRE has been validated
      against the integral route dose measurements made at commercial aircraft
      altitudes during the 49 flights. On most flights, the code gave predictions that
      agreed to the measured data (within +/- 25%), providing confidence in the use of
      PCAIRE to predict aircrew exposure to galactic cosmic radiation. An empirical
      correlation, based on ground-level neutron monitoring data, has also been
      developed for the estimation of aircrew exposure from solar energetic particle
      (SEP) events. This model has been used to determine the significance of SEP
      exposure on a theoretical jet altitude flight during GLE 42.

PMID- 16604654
TI  - FLUKA simulation of TEPC response to cosmic radiation.
AB  - The aircrew exposure to cosmic radiation can be assessed by calculation with
      codes validated by measurements. However, the relationship between doses in the
      free atmosphere, as calculated by the codes and from results of measurements
      performed within the aircraft, is still unclear. The response of a tissue
      equivalent proportional counter (TEPC) has already been simulated successfully by
      the Monte Carlo transport code FLUKA. Absorbed dose rate and ambient dose
      equivalent rate distributions as functions of lineal energy have been simulated
      for several reference sources and mixed radiation fields. The agreement between
      simulation and measurements has been well demonstrated. In order to evaluate the
      influence of aircraft structures on aircrew exposure assessment, the response of
      TEPC in the free atmosphere and on-board is now simulated. The calculated results
      are discussed and compared with other calculations and measurements.

PMID- 16604655
TI  - A mathematical model of aircraft for evaluating the effects of shielding
      structure on aircrew exposure.
AB  - To investigate the influence of the aircraft structures and contents on the
      exposure of aircrew to the galactic component of cosmic rays, a mathematical
      model of an aeroplane has been developed. The irradiation of the mathematical
      model in the cosmic ray environment has been simulated using the Monte Carlo
      transport code FLUKA. Effective dose andambient dose-equivalent rates have been
      determined inside the aircraft at several locations along the fuselage at a
      typicaI civil aviation altitude. A significant effect of the shielding of
      aircraft structures has been observed on the ambient dose-equivalent rates, while
      the impact on the effective dose rates seems to be minor. Care should be taken in
      positioning the detectors onboard when the measurements are aimed at validating
      the codes.

PMID- 16604656
TI  - Application of the heliocentric potential to aircraft dosimetry.
AB  - The heliocentric potential is the result of a steady-state solution to the
      diffusion equation of cosmic rays through the solar wind. The counting rate of
      any high-latitude, ground-level neutron monitor can be used to determine this
      potential, which will return cosmic ray spectra in real time. These spectra are
      routinely used to determine the radiation dose rate to which air crew are exposed
      during the precise hours of a flight, including the effects of quick decreases
      and Forbush decreases. Further, it has been used in an effort to calculate the
      radiation dose rate to air crew during an energetic solar particle event, as the
      cosmic ray background before the event must be determined. An alternate approach
      is to use the deceleration potential, which assumes a significant time-dependence
      of cosmic rays through the heliosphere. However, the theory behind it does not
      account for the behaviour of ground-level neutron monitors.

PMID- 16604657
TI  - A cargo inspection system based on pulsed fast neutron analysis (PFNA).
AB  - A cargo inspection system based on pulsed fast neutron analysis (PFNA) is to be
      used at a border crossing to detect explosives and contraband hidden in trucks
      and cargo containers. Neutrons are produced by the interaction of deuterons in a
      deuterium target mounted on a moveable scan arm. The collimated pulsed fast
      neutron beam is used to determine the location and composition of objects in a
      cargo container. The neutrons produce secondary gamma rays that are
      characteristic of the object's elemental composition. The cargo inspection system
      building consists of an accelerator room and an inspection tunnel. The
      accelerator room is shielded and houses the injector, accelerator and the neutron
      production gas target. The inspection tunnel is partially shielded. The truck or
      container to be inspected will be moved through the inspection tunnel by a
      conveyor system. The facility and radiation source terms considered in the
      shielding design are described.

PMID- 16604658
TI  - An airport cargo inspection system based on X-ray and thermal neutron analysis
      (TNA).
AB  - A cargo inspection system incorporating a high-resolution X-ray imaging system
      with a material-specific detection system based on Ancore Corporation's patented
      thermal neutron analysis (TNA) technology can detect bulk quantities of
      explosives and drugs concealed in trucks or cargo containers. The TNA process
      utilises a 252Cf neutron source surrounded by a moderator. The neutron
      interactions with the inspected object result in strong and unique gamma-ray
      signals from nitrogen, which is a key ingredient in modern high explosives, and
      from chlorinated drugs. The TNA computer analyses the gamma-ray signals and
      automatically determines the presence of explosives or drugs. The radiation
      source terms and shielding design of the facility are described. For the X-ray
      generator, the primary beam, leakage radiation, and scattered primary and leakage
      radiation were considered. For the TNA, the primary neutrons and tunnel scattered
      neutrons as well as the neutron-capture gamma rays were considered.

PMID- 16604659
TI  - Evaluation of the dose rate distribution for an air-type 60Co irradiation
      facility.
AB  - The dose rate distributions in the 29,000-Ci 60Co irradiation facility in
      National Tsing Hua University were investigated by measurements and calculations.
      The dose rate measurements were performed using radiochromic dye films and an
      Exradin A2 ion chamber mounted on a PC-controlled motorised vertical translation
      stage. The calculations were made by using the three-dimensional point kernel
      code QAD-CGGP with detailed source composition and geometry modelling. The
      scattered gamma rays from the walls of the irradiation cell were also evaluated
      by using the Monte Carlo code MCNP.

PMID- 16604660
TI  - A very low-background gamma-ray counting facility in the Baradello underground
      laboratory.
AB  - An underground station for the measurement of low-level radioactivity is in
      operation in Northern Italy in the town of Como under the Baradello hill. The
      rock cover is -300 m water equivalent. This paper reports about the preliminary
      measurements carried out to characterise the site of the Baradello hill and the
      installation of a high-purity Ge detector with a radio-pure copper shielding.
      Features and levels of the achieved background are reported and discussed, in
      comparison with other above ground and underground low-radioactivity stations.
      Sensitivities to radioactivity in typical environmental matrices are evaluated,
      confirming the very low-gamma background attained in the laboratory.

PMID- 16604661
TI  - Locating liquid and gas interfaces behind a steel hull: a neutron backscatter
      tool in action.
AB  - Monte Carlo simulations were performed to prove that a neutron backscatter tool
      can detect liquid (hydrocarbon or water) and gas levels behind steel casings,
      even when used under water. Consequently such a tool can be applied to the
      detection of fluid levels in wrecked vessels, which is important for
      environmentally safe retrieval of oil in these vessels. These simulations enable
      the efficient optimisation of the experimental conditions, without having to
      resort to expensive mock-ups.

PMID- 16604662
TI  - Measurements of radiation fields around high-energy proton accelerators.
AB  - Monitoring of ionising radiation around high-energy particle accelerators is a
      difficult task due to the complexity of the radiation field, which is made up of
      neutrons, charged hadrons, muons, photons and electrons, with energy spectra
      extending over a wide energy range. The dose-equivalent outside a thick shield is
      mainly owing to neutrons, with some contribution from photons and, to a minor
      extent, the other particles. Neutron dosimetry and spectrometry are thus of
      primary importance to correctly evaluate the exposure of personnel. This paper
      reviews the relevant techniques and instrumentation employed for monitoring
      radiation fields around high-energy proton accelerators, with particular emphasis
      on the recent development to increase the response of neutron measuring devices >
      20 MeV. Rem-counters, pressurised ionisation chambers, superheated emulsions,
      tissue-equivalent proportional counters and Bonner sphere spectrometers are
      discussed.

PMID- 16604663
TI  - Space radiation measurements on-board ISS--the DOSMAP experiment.
AB  - The experiment 'Dosimetric Mapping' conducted as part of the science program of
      NASA's Human Research Facility (HRF) between March and August 2001 was designed
      to measure integrated total absorbed doses (ionising radiation and neutrons),
      heavy ion fluxes and its energy, mass and linear energy transfer (LET) spectra,
      time-dependent count rates of charged particles and their corresponding dose
      rates at different locations inside the US Lab at the International Space
      Station. Owing to the variety of particles and energies, a dosimetry package
      consisting of thermoluminescence dosemeter (TLD) chips and nuclear track
      detectors with and without converters (NTDPs), a silicon dosimetry telescope
      (DOSTEL), four mobile silicon detector units (MDUs) and a TLD reader unit (PILLE)
      with 12 TLD bulbs as dosemeters was used. Dose rates of the ionising part of the
      radiation field measured with TLD bulbs applying the PILLE readout system at
      different locations varied between 153 and 231 microGy d(-1). The dose rate
      received by the active devices fits excellent to the TLD measurements and is
      significantly lower compared with measurements for the Shuttle (STS) to MIR
      missions. The comparison of the absorbed doses from passive and active devices
      showed an agreement within +/- 10%. The DOSTEL measurements in the HRF location
      yielded a mean dose equivalent rate of 535 microSv d(-1). DOSTEL measurements
      were also obtained during the Solar Particle Event on 15 April 2001.

PMID- 16604664
TI  - Simulation and measurements of the response of an air ionisation chamber exposed
      to a mixed high-energy radiation field.
AB  - CERN's radiation protection group operates a network of simple and robust
      ionisation chambers that are installed inside CERN's accelerator tunnels. These
      ionisation chambers are used for the remote reading of ambient dose rate
      equivalents inside the machines during beam-off periods. This Radiation
      Protection Monitor for dose rates due to Induced Radioactivity ('PMI', trade
      name: PTW, Type 34031) is a non-confined air ionisation plastic chamber which is
      operated under atmospheric pressure. Besides its current field of operation it is
      planned to extend the use of this detector in the Large Hadron Collider to
      measure radiation under beam operation conditions to obtain an indication of the
      machine performance. Until now, studies of the PMI detector have been limited to
      the response to photons. In order to evaluate its response to other radiation
      components, this chamber type was tested at CERF, the high-energy reference field
      facility at CERN. Six PMI detectors were installed around a copper target being
      irradiated by a mixed hadron beam with a momentum of 120 GeV c(-1). Each of the
      chosen detector positions was defined by a different radiation field, varying in
      type and energy of the incident particles. For all positions, detailed
      measurements and FLUKA simulations of the detector response were performed. This
      paper presents the promising comparison between the measurements and simulations
      and analyses the influence of the different particle types on the resulting
      detector response.

PMID- 16604665
TI  - Adaptive response by single cell radiation hits--implications for nuclear
      workers.
AB  - Several radiobiology mechanisms show an ability of cells to activate protective
      mechanisms against the deleterious effects of ionizing radiations. The most
      interesting with respect to possible health benefits to humans is the phenomenon
      of adaptive response (AR). Fundamentally AR must be shown to be operative at very
      low doses and dose rates experienced during human radiation environment
      activities. A microdosimetric model is presented which, by the use of Poisson
      cell nucleus hit accumulation, enables examination of the single hit range of
      radiation exposure where the AR radio-protection is first activated. It is found,
      with the model, that single charged particle tract specific energy hits to the
      nucleus can activate AR. Both in vitro and in vivo data reported here indicated
      that AR may provide a reduction in cancer-causing DNA damage, from both radiation
      and spontaneous events, for nuclear workers and general public diagnostic
      treatments.

PMID- 16604666
TI  - Application of a sitting MIRD phantom for effective dose calculations.
AB  - In typical realistic scenarios, dose factors due to 60Co contaminated steel, used
      in consumer products, cannot be approximated by standard exposure geometries. It
      is then necessary to calculate the effective dose using an appropriate
      anthropomorphic phantom. MCNP calculations were performed using a MIRD human
      model in two settings. In the first, a male office worker is sitting in a chair
      containing contaminated steel, surrounded by contaminated furniture. In the
      second, a male driver is seated inside an automobile, the steel of which is
      uniformly contaminated. To accurately calculate the dose to lower body organs,
      especially the gonads, it was essential to modify the MIRD model to simulate two
      sitting postures: chair and driving position. The phantom modifications are
      described, and the results of the calculations are presented. In the case of the
      automobile scenarios, results are compared to those obtained using an isotropic
      fluence-to-dose conversion function.

PMID- 16604668
TI  - Characterisation of radionuclides formed by high-energy neutron irradiation.
AB  - The physicochemical properties of radionuclides suspended in the air are
      important parameters in order to evaluate internal doses due to the inhalation of
      the airborne radionuclides and to develop the air-monitoring system in high
      energy proton accelerator facilities. This study focuses on the property of
      radioactive airborne chlorine (38Cl and 39Cl) and sulphur (38S) produced in Ar
      gas by irradiation with high-energy neutrons. As a result of the irradiation of a
      mixture of Ar gas and dry air, 38Cl and 39Cl existed as non-acidic gas and 38S
      was present as acidic gas. Furthermore, it has been found that in the high-energy
      neutron irradiation of aerosol containing Ar gas, the higher the amount of
      radioactive aerosols, the lower will be the amount of radioactive acidic gas.

PMID- 16604667
TI  - Modelling of the mammographic exposure conditions for radiological detriment
      study in the Valencian Breast Cancer Screening Programme.
AB  - Breast screening programmes are the best weapon to fight against breast cancer.
      Nevertheless, despite the benefits, this practice supposes a radiological risk
      that cannot be forgotten. In order to calculate breast glandular doses, different
      MCNP-4C2 models have been developed, simulating the exposure conditions.
      Radiological detriments have been transported from the population under study in
      the UNSCEAR 2000 to the Valencian Community, obtaining the detection-induced
      cancer ratio (DICR) for this population.

PMID- 16604669
TI  - Modelling of neutron survey instrument performance and experimental validation of
      those calculated response data.
AB  - Three moderator-type neutron survey instruments have been modelled for energy and
      angle dependence of the response, in greater detail than before. These response
      data have been verified by comparison with published experimental measurements
      and measurements made specifically for this project. Influences on the instrument
      response have also been investigated. These have included its mode-of-use and
      perturbations caused by variations in the instrument manufacture. The
      implications of these new response data have been assessed by an extensive
      programme of folding the responses with workplace energy distributions.

PMID- 16604671
TI  - Interim storage of spent and disused sealed sources: optimisation of external
      dose distribution in waste grids using the MCNPX code.
AB  - Radioactive sealed sources are in use worldwide in different fields of
      application. When no further use is foreseen for these sources, they become spent
      or disused sealed sources and are subject to a specific waste management scheme.
      Portugal does have a Radioactive Waste Interim Storage Facility where spent or
      disused sealed sources are conditioned in a cement matrix inside concrete drums
      and following the geometrical disposition of a grid. The gamma dose values around
      each grid depend on the drum's enclosed activity and radionuclides considered, as
      well as on the drums distribution in the various layers of the grid. This work
      proposes a method based on the Monte Carlo simulation using the MCNPX code to
      estimate the best drum arrangement through the optimisation of dose distribution
      in a grid. Measured dose rate values at 1 m distance from the surface of the
      chosen optimised grid were used to validate the corresponding computational grid
      model.

PMID- 16604670
TI  - ISFSI site boundary radiation dose rate analyses.
AB  - Across the globe nuclear utilities are in the process of designing and analysing
      Independent Spent Fuel Storage Installations (ISFSI) for the purpose of above
      ground spent-fuel storage primarily to mitigate the filling of spent-fuel pools.
      Using a conjoining of discrete ordinates transport theory (DORT) and Monte Carlo
      (MCNP) techniques, an ISFSI was analysed to determine neutron and photon dose
      rates for a generic overpack, and ISFSI pad configuration and design at distances
      ranging from 1 to -1700 m from the ISFSI array. The calculated dose rates are
      used to address the requirements of 10CFR72.104, which provides limits to be
      enforced for the protection of the public by the NRC in regard to ISFSI
      facilities. For this overpack, dose rates decrease by three orders of magnitude
      through the first 200 m moving away from the ISFSI. In addition, the
      contributions from different source terms changes over distance. It can be
      observed that although side photons provide the majority of dose rate in this
      calculation, scattered photons and side neutrons take on more importance as the
      distance from the ISFSI is increased.

PMID- 16604672
TI  - Modelling of the shielding capabilities of the existing solid radioactive waste
      storages at Ignalina NPP.
AB  - There is only one nuclear power plant in Lithuania--Ignalina NPP (INPP). The INPP
      operates two similar units with design electrical power of 1500 MW. The units
      were commissioned in 1983 and 1987 respectively. From the beginning of the INPP
      operation all generated solid radioactive waste was collected and stored at the
      Soviet type solid radwaste facility located at INPP site. The INPP solid radwaste
      storage facility consists of four buildings, namely building No. 155, No. 155/1,
      No. 157 and No. 157/1. The buildings of the INPP solid radwaste storage facility
      are reinforced concrete structures above ground. State Nuclear Safety
      Inspectorate (VATESI) has specified that particular safety analysis must be
      performed for existing radioactive waste storage facilities of the INPP. As part
      of the safety analysis, shielding capabilities of the walls and roofs of these
      buildings were analysed. This paper presents radiation shielding analysis of the
      buildings No. 157 and No. 157/1 that are still in operation. The buildings No.
      155 and No. 155/1 are already filled up with the waste and no additional waste
      loading is expected.

PMID- 16604673
TI  - Calculation of absorbed dose around a facility for disposing of low activity
      natural radioactive waste (C3-dump).
AB  - A C3-dump is a facility for disposing of low activity natural radioactive waste
      containing the uranium series 238U, the thorium series 232Th and 40K. Only the
      external radiation owing to gamma rays, X-rays and annihilation photons is
      considered in this study. For two situations--the semi-infinite slab and the
      tourist geometry--the conversion coefficients from specific activity to air kerma
      rate at 1 m above the relevant level are calculated. In the first situation the
      waste material is in contact with the air but in the tourist geometry it is
      covered with a 1.35 m thick layer. For the calculations, the Monte Carlo
      radiation transport code MCNP is used. The yield and photon energy for each
      radionuclide are according to the database of Oak Ridge National Laboratory. For
      the tourist situation, the depth-dose distribution through the covering layer is
      calculated and extrapolated to determine the exit dose.

PMID- 16604674
TI  - MYRRHA, a Pb-Bi experimental ADS: specific approach to radiation protection
      aspects.
AB  - Since 1998, SCK*CEN, in partnership with IBA s.a. and many European research
      laboratories, is designing a multipurpose accelerator driven system (ADS) for
      Research and Development (R&D) applications-MYRRHA-and is conducting an
      associated R&D support programme. MYRRHA is an ADS under development at Mol in
      Belgium and is aiming to serve as a basis for the European experimental ADS to
      provide protons and neutrons for various R&D applications. It consists of a
      proton accelerator delivering a 350 MeV x 5 mA proton beam to a liquid Pb-Bi
      spallation target that in turn couples to a Pb-Bi cooled, subcritical fast core.
      In the first stage, the project focuses mainly on demonstration of the ADS
      concept, safety research on sub-critical systems and nuclear waste transmutation
      studies. In a later stage, the device will also be dedicated to research on
      structural materials, nuclear fuel, liquid metal technology and associated
      aspects, and on sub-critical reactor physics. Subsequently, it will be used for
      research on applications such as radioisotope production. A first preliminary
      conceptual design file of MYRRHA was completed by the end of 2001 and has been
      reviewed by an International Technical Guidance Committee, which concluded that
      there are no show stoppers in the project and even though some topics such as the
      safety studies and the fuel qualification need to be addressed more deeply before
      concluding it. In this paper, we are reporting on the state-of-the art of the
      MYRRHA project at the beginning of 2004 and in particular on the radiation
      shielding assessment and the radiation protection particular aspects through a
      remote handling operation approach in order to minimise the personnel exposure to
      radiation.

PMID- 16604675
TI  - The PDS-XADS reference accelerator and its radioprotection issues.
AB  - At the start-up of the FP5 project PDS-XADS, the main initial specifications for
      the accelerator system (e.g. beam energy, beam intensity, beam profile, their
      stability and the accelerator availability and reliability) have been defined by
      Working Package 1 (WP1), 'Global Coherence', in connection with the other WPs of
      the project. From this, WP3 ('The Accelerator') has assessed the main
      requirements and the corresponding technical answers. A reference solution, based
      on a linear superconducting accelerator with its associated doubly achromatic
      beam line has been worked out to some detail. For high reliability, the proposed
      design is intrinsically fault tolerant, relying on highly modular 'de-rated'
      components associated with a fast digital feedback system. The proposed solution
      also appears to be robust in terms of operational aspects like maintenance and
      radioprotection. A programme for the remaining R&D required has been elaborated
      and is proposed within the FP6 project EUROTRANS.

PMID- 16604676
TI  - Investigation of radiation fields outside the Sub-critical Assembly in Dubna.
AB  - The radiation fields outside the planned experimental Sub-critical Assembly in
      Dubna (SAD) have been studied in order to provide a basis for the design of the
      concrete shielding that cover the reactor core. The effective doses around the
      reactor, induced by leakage of neutrons and photons through the shielding, have
      been determined for a shielding thickness varying from 100 to 200 cm. It was
      shown that the neutron flux and the effective dose is higher above the shielding
      than at the side of it, owing to the higher fraction of high-energy spallation
      neutrons emitted in the direction of the incident beam protons. At the top, the
      effective dose was found to be -150 microSv s(-1) for a concrete thickness of 100
      cm, while -2.5 microSv s(-1) for a concrete thickness of 200 cm. It was also
      shown that the high-energy neutrons (> 10 MeV), which are created in the proton
      induced spallation interactions in the target, contribute for the major part of
      the effective doses outside the reactor.

PMID- 16604677
TI  - 106Ru/106Rh plaque and proton radiotherapy for ocular melanoma: a comparative
      dosimetric study.
AB  - The objective of this study was to perform comparative dosimetric studies of both
      106Ru/106Rh plaque brachytherapy and external beam proton therapy proposed for
      ocular treatments at the University of Texas M. D. Anderson Cancer Center,
      Houston, TX, USA. These modalities were also compared with traditional 125I
      plaque brachytherapy. Using a standardised eye model with a representative ocular
      melanoma tumour, the relative dose distributions within the tumour and
      surrounding tissue were calculated using the Monte Carlo code MCNPX. Published
      absorbed dose distributions benchmarked the Monte Carlo models. Results indicate
      that the proton beam provided superior dose uniformity within the tumour volume,
      whereas the dose distribution from 106Ru/106Rh was more heterogeneous. Relative
      to 125I COMS plaque, both 106Ru/106Rh and protons have shown more confined dose
      distributions to the tumour volume in this situation, thus sparing other critical
      ocular structures. For protons, it has been shown that only doses lower than the
      maximum dose are delivered outside the tumour volume. Depending on the clinical
      situation, this may aid in the sparing of critical structures located in the
      sclera and optic disc boundary. The Monte Carlo model's statistical uncertainties
      of the mean dose estimates for the 106Ru/106Rh plaque and proton beam were 3 and
      2.5%, respectively.

PMID- 16604679
TI  - The microdosimetry of boron neutron capture therapy in a randomised ellipsoidal
      cell geometry.
AB  - Two reactions deliver the majority of local dose in boron neutron capture
      therapy. The ionised particles (protons, alpha particles and lithium nuclei)
      produced in the two reactions, 10B(n,alpha,gamma)7Li and 14N(n,p)14O, have short
      ranges that are less than -14 microm (which is on the order of the diameter of a
      typical human cell). The ionised particles are heavy and are in the 2+ charge
      state in the case of the boron reactions. These heavy 2+ ions will do significant
      damage to molecules near their tracks. Thus, the distribution of nitrogen and, in
      particular, of boron determines the spatial characteristics of the radiation
      field. Since the distribution of nitrogen is nearly homogeneous in the brain and
      is not easily altered for the purpose of radiotherapy, the spatial variation in
      the radiation dose is due mainly to the spatial distribution of boron. This
      implies that the spatial distribution of boron determines the microscopic energy
      deposition and therefore the spatial characteristics of the microscopic dose. The
      microscopic dose from the (n,alpha) and (n,p) reactions has been examined in
      detail and, as averred, the proton dose is relatively homogeneous except for
      statistical variability. The statistical variability in essence adds a false
      spatial variability that would not be seen if a large number of histories were
      performed. Since the majority of spatial variability occurs in the boron
      distribution, the (n,p) reaction can be suppressed to better understand the
      spatial distribution effects on the microscopic dose. Programs have been written
      in FORTRAN using Monte Carlo techniques to model ellipsoidal cells that are
      either randomly sized and located in the region of interest or are arranged in a
      face centred cubic array and are identical except for the location of the nuclei,
      which may be random. It is shown that closely packed prolate ellipsoidal cells
      with a large eccentricity in one dimension will receive a larger nuclear dose
      than cells that are more sparsely packed. This demonstrates that the boron
      content of a cell and its nucleus can have a significant impact upon the dose to
      neighbouring cells. The local boron distribution in a region of interest can be
      shown to affect the macrodosimetric dose, with possible implications for clinical
      outcomes.

PMID- 16604678
TI  - Comparison of treatment planning dose calculations with measurements and Monte
      Carlo calculations in a RANDO phantom.
AB  - Solid tumours are often treated with external beams of photons generated by
      Bremsstrahlung radiation. These beams are shaped and filtered to optimise the
      dose to specific regions defined by the treatment plans, which may involve
      irradiations from multiple angles. It is important that doses to healthy tissue
      do not exceed tolerance doses and that the dose to the tumour is maximised. To
      accomplish these objectives, commercially available 3-D treatment planning
      software is used to calculate doses to healthy tissue and to the tumour. It is
      generally believed that these commercial software packages calculate doses
      through the patient to within a few per cent. In order to examine this claim,
      dose calculations obtained from ADAC software for external beam treatment to the
      pelvic region of a RANDO phantom are compared with 37 thermoluminescence
      dosemeters placed into several slices of a RANDO phantom. The phantom was
      irradiated to obtain a prescription dose of 180 cGy at the tumour location. Data
      from homogeneous regions agree within several per cent with results obtained from
      ADAC software, whereas this comparison is less favourable in regions of
      heterogeneity. Results from Monte Carlo calculations in a homogeneous phantom are
      comparable to results from ADAC treatment planning software.

PMID- 16604680
TI  - Filter, collimator and moderating material to achieve boron neutron capture
      enhanced fast neutron therapy.
AB  - The combination of fast neutron therapy and boron neutron capture therapy is
      currently being studied as a possible treatment for some radio-resistant brain
      tumours. In an attempt to design a boron-enhanced fast neutron therapy beam for
      the Fermilab Fast Neutron Therapy Facility, the use of moderating material
      surrounding the patient's head has been investigated. Graphite, polyethylene,
      water and heavy water were studied as moderating materials, using MCNP. The use
      of tungsten, iron, lead and bismuth as materials for a small filter and
      collimator near the patient's head was investigated. Calculations showed that a
      filter and collimator made of tungsten with a graphite moderator was capable of
      producing a dose enhancement of 17.3 +/- 0.6% for a 100 microg g(-1) loading of
      10B for a 5.6 cm diameter beam while delivering 1.5 Gy in 7 min.

PMID- 16604681
TI  - Monte Carlo optimisation of a BNCT facility for treating brain gliomas at the
      TAPIRO reactor.
AB  - An epithermal boron neutron capture therapy facility for treating brain gliomas
      is currently under construction at the 5 kW fast-flux reactor TAPIRO located at
      ENEA, Casaccia, near Rome. In this work, the sensitivity of the results to the
      boron concentrations in healthy tissue and tumour is investigated and the change
      in beam quality on modifying the moderator thickness (within design limits) is
      studied. The Monte Carlo codes MCNP and MCNPX were used together with the DSA in
      house variance reduction patch. Both usual free beam parameters and the in
      phantom treatment planning figures-of-merit have been calculated in a realistic
      anthropomorphic phantom ('ADAM').

PMID- 16604682
TI  - An inverse method for radiation transport.
AB  - Adjoint functions have been used with forward functions to compute gradients in
      implicit (iterative) solution methods for inverse problems in optical tomography,
      geoscience, thermal science and other fields, but only once has this approach
      been used for inverse solutions to the Boltzmann transport equation. In this
      paper, this approach is used to develop an inverse method that requires only
      angle-independent flux measurements, rather than angle-dependent measurements as
      was done previously. The method is applied to a simplified form of the transport
      equation that does not include scattering. The resulting procedure uses measured
      values of gamma-ray fluxes of discrete, characteristic energies to determine
      interface locations in a multilayer shield. The method was implemented with a
      Newton-Raphson optimisation algorithm and it worked very well in numerical 1-D
      spherical test cases. A more sophisticated optimisation method would better
      exploit the potential of the inverse method.

PMID- 16604683
TI  - Monte Carlo modelling of a simple accident dosemeter.
AB  - A simple dosemeter made of a sulphur tablet, bare and cadmium-covered indium
      foils and a cadmium-covered copper foil has been modelled using MCNP5. Studies of
      the model without phantoms or other confounding factors have shown that the cross
      sections and fluence-to-dose factors generated by the Monte Carlo method agree
      with those generated by analytic expressions for the high-energy component. In
      this study, the effect of location on phantoms is studied and an extension of
      this study to low and intermediate energies is done. The activities expected from
      exposure to four critical assemblies on phantom is calculated and compared with
      observations.

PMID- 16604684
TI  - An iterative method for calculating gamma-ray build-up factors in multi-layer
      shields.
AB  - Point kernel codes that simulate gamma-ray transport often use build-up factors
      to take scattered photons into account. This study introduces a new method, for
      computing multi-layer shield build-up factors. This method, based on an empirical
      formula for calculating double-layer shield build-up factors, is iterative. For
      an N-layer shield, each iteration of the method treats the first and the second
      layer of the shield. It replaces these layers by a single equivalent layer
      composed of an appropriate material and, hence, it turns the N-layer shield into
      an (N - 1)-layer shield. In order to determine the equivalent layer of an
      appropriate material, a neural network approach is developed: some neural
      networks trained on a large set of various configurations provide the equivalent
      material for any double-layer configuration. The method is implemented into
      MERCURE-6.3 straight-line attenuation code and is validated by comparison between
      MERCURE-6.3 results and reference data for one-dimensional geometries. Reference
      data obtained from transport calculations performed using the Sn transport code
      TWODANT. The comparisons prove the accuracy and sturdiness of the method.

PMID- 16604685
TI  - Performance of the improved version of monte Carlo code A3MCNP for large-scale
      shielding problems.
AB  - A3MCNP (Automatic Adjoint Accelerated MCNP) is a revised version of the MCNP
      Monte Carlo code, which automatically prepares variance reduction parameters for
      the CADIS (Consistent Adjoint Driven Importance Sampling) methodology. Using a
      deterministic 'importance' (or adjoint) function, CADIS performs source and
      transport biasing within the weight-window technique. The current version of
      A3MCNP uses the three-dimensional (3-D) Sn transport TORT code to determine a 3-D
      importance function distribution. Based on simulation of several real-life
      problems, it is demonstrated that A3MCNP provides precise calculation results
      with a remarkably short computation time by using the proper and objective
      variance reduction parameters. However, since the first version of A3MCNP
      provided only a point source configuration option for large-scale shielding
      problems, such as spent-fuel transport casks, a large amount of memory may be
      necessary to store enough points to properly represent the source. Hence, we have
      developed an improved version of A3MCNP (referred to as A3MCNPV) which has a
      volumetric source configuration option. This paper describes the successful use
      of A3MCNPV for a concrete cask neutron and gamma-ray shielding problem, and a PWR
      dosimetry problem.

PMID- 16604686
TI  - Implementation of variance-reduction techniques for Monte Carlo nuclear logging
      calculations with neutron sources.
AB  - Monte Carlo simulations for nuclear logging applications are considered to be
      highly demanding transport problems. In this paper, the implementation of weight
      window variance reduction schemes in a 'manual' fashion to improve the efficiency
      of calculations for a neutron logging tool is presented. The simulations were
      conducted using MCNP to assess the sensitivity of neutron and gamma flux to the
      saturation of soil with fresh and salty water and oil. The weight-windows were
      optimised to enhance the precision in characteristic gamma-ray windows for carbon
      oxygen logging and sigma logging. An analysis is under way to incorporate quartz
      sediments and other oil substances. Future tasks include the assessment of
      advanced Monte Carlo estimators and optimisation of capture gamma-ray sampling
      techniques to enhance the variance reduction in nuclear logging calculations.

PMID- 16604687
TI  - Effective biasing schemes for duct streaming problems.
AB  - The effective use of biasing for the Monte Carlo solution of a void streaming
      problem is essential to obtaining a reasonable result in a reasonable amount of
      time. Most general purpose Monte Carlo shielding codes allow for the user to
      select the particular biasing techniques best oriented to the particular problem
      of interest. The biasing strategy for void streaming problems many times differs
      from that of a deep penetration problem. The key in void streaming is to bias
      particles into the streaming path, whereas in deep penetration problems the
      biasing is aimed at forcing particles through the shield. Until recently, the
      biasing scheme in the SCALE SAS4 shielding module was considered inadequate for
      void streaming problems due to the assumed one-dimensional nature of the
      automated bias prescription. A modified approach to the automated biasing in SAS4
      has allowed for significant gains to be realised in the use of the code for void
      streaming problems. This paper applies the modified SAS4 procedures to a spent
      fuel storage cask model with vent ports. The results of the SAS4 analysis are
      compared with those of the ADVANTG methodology, which is an accelerated version
      of MCNP. Various options available for the implementation of the SAS4 methodology
      are reviewed and recommendations offered.

PMID- 16604688
TI  - Automated variance reduction for MCNP using deterministic methods.
AB  - In order to reduce the user's time and the computer time needed to solve deep
      penetration problems, an automated variance reduction capability has been
      developed for the MCNP Monte Carlo transport code. This new variance reduction
      capability developed for MCNP5 employs the PARTISN multigroup discrete ordinates
      code to generate mesh-based weight windows. The technique of using deterministic
      methods to generate importance maps has been widely used to increase the
      efficiency of deep penetration Monte Carlo calculations. The application of this
      method in MCNP uses the existing mesh-based weight window feature to translate
      the MCNP geometry into geometry suitable for PARTISN. The adjoint flux, which is
      calculated with PARTISN, is used to generate mesh-based weight windows for MCNP.
      Additionally, the MCNP source energy spectrum can be biased based on the adjoint
      energy spectrum at the source location. This method can also use angle-dependent
      weight windows.

PMID- 16604689
TI  - TORT/MCNP coupling method for the calculation of neutron flux around a core of
      BWR.
AB  - For the analysis of BWR neutronics performance, accurate data are required for
      neutron flux distribution over the In-Reactor Pressure Vessel equipments taking
      into account the detailed geometrical arrangement. The TORT code can calculate
      neutron flux around a core of BWR in a three-dimensional geometry model, but has
      difficulties in fine geometrical modelling and lacks huge computer resource. On
      the other hand, the MCNP code enables the calculation of the neutron flux with a
      detailed geometry model, but requires very long sampling time to give enough
      number of particles. Therefore, a TORT/MCNP coupling method has been developed to
      eliminate the two problems mentioned above in each code. In this method, the TORT
      code calculates angular flux distribution on the core surface and the MCNP code
      calculates neutron spectrum at the points of interest using the flux
      distribution. The coupling method will be used as the DOT-DOMINO-MORSE code
      system. This TORT/MCNP coupling method was applied to calculate the neutron flux
      at points where induced radioactivity data were measured for 54Mn and 60Co and
      the radioactivity calculations based on the neutron flux obtained from the above
      method were compared with the measured data.

PMID- 16604690
TI  - Declassification of radioactive liquid wastes generated in radio immune assay
      [corrected] (RIA) laboratories.
AB  - Radioactive liquid wastes of low-medium activity level are generated in radio
      immune assay (RIA) laboratories, which are also potentially infectious because of
      the pathogens from patient blood. The most common way of managing these wastes
      consists of a temporal storage, for partial radioactivity decay, followed by
      management by an authorised company. The object of this work is to study the
      viability of treating radioactive liquid wastes coming from RIA using membrane
      techniques in order to reduce their volume, which would mean an improvement from
      the radiological point of view and a decrease in management costs. This paper
      describes the results of some experiments carried out with RIA real wastes, by
      means of processes such as ultrafiltration and reverse osmosis. It has been
      proved that waste volume can be significantly reduced, obtaining a treated liquid
      that is free of pathogens and organic matter and with an activity level around
      the environmental background.

PMID- 16604691
TI  - Estimate of radiation damage to low-level electronics of the RF system in the LHC
      cavities arising from beam gas collisions.
AB  - Monte Carlo simulations have been performed to estimate the radiation damage
      induced by high-energy hadrons in the digital electronics of the RF low-level
      systems in the LHC cavities. High-energy hadrons are generated when the proton
      beams interact with the residual gas. The contributions from various elements
      vacuum chambers, cryogenic cavities, wideband pickups and cryomodule beam tubes
      have been considered individually, with each contribution depending on the gas
      composition and density. The probability of displacement damage and single event
      effects (mainly single event upsets) is derived for the LHC start-up conditions.

PMID- 16604692
TI  - A comparison of skyshine computational methods.
AB  - A variety of methods employing radiation transport and point-kernel codes have
      been used to model two skyshine problems. The first problem is a 1 MeV point
      source of photons on the surface of the earth inside a 2 m tall and 1 m radius
      silo having black walls. The skyshine radiation downfield from the point source
      was estimated with and without a 30-cm-thick concrete lid on the silo. The second
      benchmark problem is to estimate the skyshine radiation downfield from 12
      cylindrical canisters emplaced in a low-level radioactive waste trench. The
      canisters are filled with ion-exchange resin with a representative radionuclide
      loading, largely 60Co, 134Cs and 137Cs. The solution methods include use of the
      MCNP code to solve the problem by directly employing variance reduction
      techniques, the single-scatter point kernel code GGG-GP, the QADMOD-GP point
      kernel code, the COHORT Monte Carlo code, the NAC International version of the
      SKYSHINE-III code, the KSU hybrid method and the associated KSU skyshine codes.

PMID- 16604693
TI  - Skyshine analysis using energy and angular dependent dose-contribution fluxes
      obtained from air-over-ground adjoint calculation.
AB  - A generalised and convenient skyshine dose analysis method has been developed
      based on forward-adjoint folding technique. In the method, the air penetration
      data were prepared by performing an adjoint DOT3.5 calculation with cylindrical
      air-over-ground geometry having an adjoint point source (importance of unit flux
      to dose rate at detection point) in the centre. The accuracy of the present
      method was certified by comparing with DOT3.5 forward calculation. The adjoint
      flux data can be used as generalised radiation skyshine data for all sorts of
      nuclear facilities. Moreover, the present method supplies plenty of energy
      angular dependent contribution flux data, which will be useful for detailed
      shielding design of facilities.

PMID- 16604694
TI  - The skyshine benchmark experiment revisited.
AB  - With the coming renaissance of nuclear power, heralded by new nuclear power plant
      construction in Finland, the issue of qualifying modern tools for calculation
      becomes prominent. Among the calculations required may be the determination of
      radiation levels outside the plant owing to skyshine. For example, knowledge of
      the degree of accuracy in the calculation of gamma skyshine through the turbine
      hall roof of a BWR plant is important. Modern survey programs which can calculate
      skyshine dose rates tend to be qualified only by verification with the results of
      Monte Carlo calculations. However, in the past, exacting experimental work has
      been performed in the field for gamma skyshine, notably the benchmark work in
      1981 by Shultis and co-workers, which considered not just the open source case
      but also the effects of placing a concrete roof above the source enclosure. The
      latter case is a better reflection of reality as safety considerations nearly
      always require the source to be shielded in some way, usually by substantial
      walls but by a thinner roof. One of the tools developed since that time, which
      can both calculate skyshine radiation and accurately model the geometrical set-up
      of an experiment, is the code RANKERN, which is used by Framatome ANP and other
      organisations for general shielding design work. The following description
      concerns the use of this code to re-address the experimental results from 1981.
      This then provides a realistic gauge to validate, but also to set limits on, the
      program for future gamma skyshine applications within the applicable licensing
      procedures for all users of the code.

PMID- 16604695
TI  - Experiment and analyses for 14 MeV neutron streaming through a dogleg duct.
AB  - There are several vacant channels for diagnosis, RF heating and so on through the
      shielding structure in fusion reactors. Some of them consist of dogleg ducts,
      through which neutrons stream in a complex manner. An experiment was conducted
      with the Fusion Neutronics Source (FNS) facility at JAERI to study the behaviour
      of neutrons in the duct and assess the reliability of calculation methods for the
      design of fusion reactors such as ITER. The assembly was an iron slab 180 cm in
      thickness with a doubly bent duct 30 x 30 cm2 in cross section. The experiment
      was analysed using a simple design code for radiation streaming, DUCT-III, and
      the Monte Carlo code MCNP. The results indicate that the simple design code is
      reliable enough to be used for shielding design analyses as well as the Monte
      Carlo method, which showed excellent agreement between calculated and measured
      values.

PMID- 16604696
TI  - Simulation of medical electron linac bremsstrahlung beam transport in typical
      shielding materials.
AB  - The Monte Carlo N-particle code MCNP version 4C3 was used to investigate the
      backscattering and transmission of high-energy photons in concrete, iron and lead
      at deep penetration. A typical bremsstrahlung beam from a 24 MV linac was used,
      and the transmission up to 15 mean-free paths was studied. Broad beam slab
      geometry was used. Estimates of the transmission in terms of absorbed dose to
      tissue ratio and air kerma ratio were performed for the primary and secondary
      components of the transmitted beam in the three materials. The tissue dose and
      air kerma buildup factors were calculated and fitted to Berger's equation.
      Finally, the differential dose albedo values for common reflected angles were
      determined.

PMID- 16604697
TI  - Arrangement of high-energy neutron irradiation field and shielding experiment
      using 4 m concrete at KENS.
AB  - An irradiation field of high-energy neutrons produced in the forward direction
      from a thick tungsten target bombarded by 500 MeV protons was arranged at the
      KENS spallation neutron source facility. In this facility, shielding experiment
      was performed with an ordinary concrete shield of 4 m thickness assembled in the
      irradiation room, 2.5 m downstream from the target centre. Activation detectors
      of bismuth, aluminium, indium and gold were inserted into eight slots inside the
      shield and attenuations of neutron reaction rates were obtained by measurements
      of gamma-rays from the activation detectors. A MARS14 Monte Carlo simulation was
      also performed down to thermal energy, and comparisons between the calculations
      and measurements show agreements within a factor of 3. This neutron field is
      useful for studies of shielding, activation and radiation damage of materials for
      high-energy neutrons, and experimental data are useful to check the accuracies of
      the transmission and activation calculation codes.

PMID- 16604698
TI  - Radiation shielding and dosimetry experiments updates in the SINBAD database.
AB  - The Shielding Integral Benchmark Archive Database (SINBAD) is an internationally
      established set of radiation shielding and dosimetry data related to experiments
      relevant in reactor shielding, fusion blanket neutronics and accelerator
      shielding. In addition to the characterisation of the radiation source, it
      describes shielding materials and instrumentation and the relevant detectors. The
      experimental results, be it dose or reaction rates, or unfolded spectra, are
      presented in tabular ASCII form that can easily be exported to different computer
      environments for further use. Most sets in SINBAD also contain the computer model
      used for the interpretation of the experiment and, where available, results from
      uncertainty analysis. This is an international effort between the Organization
      for Economic Cooperation and Development, Nuclear Energy Agency Data Bank
      (http://www.nea.fr/html/databank/) (OECD/NEA Data Bank) and Oak Ridge National
      Laboratory, Radiation Safety Information Computational Center (http://www
      rsicc.ornl.gov/rsic.html) (ORNL/RSICC). Cooperation from many organisations,
      authors and benchmark analysts have helped SINBAD become a 'living database'--one
      which involves continuous information updates, preservation and additions of
      nuclear benchmarks in the areas of fusion, fission and accelerator science and
      engineering. This paper focuses on the increased comprehensiveness of experiments
      that have been carried out in recent years and the validation of computer code
      and cross section library using these experiments.

PMID- 16604699
TI  - MCNP simulation to optimise in-pile and shielding parts of the Portuguese SANS
      instrument.
AB  - A Small Angle Neutron Scattering instrument is being installed at one end of the
      tangential beam tube of the Portuguese Research Reactor. The instrument is fed
      using a neutron scatterer positioned in the middle of the beam tube. The
      scatterer consists of circulating H2O contained in a hollow disc of Al. The in
      pile shielding components and the shielding installed around the neutron selector
      have been the object of an MCNP simulation study. The quantities calculated were
      the neutron and gamma-ray fluxes in different positions, the energy deposited in
      the material by the neutron and gamma-ray fields, the material activation
      resulting from the neutron field and radiation doses at the exit wall of the
      shutter and around the shielding. The MCNP results are presented and compared
      with results of an analytical approach and with experimental data collected after
      installation.

PMID- 16604700
TI  - The shielding design process--new plants to decommissioning.
AB  - BNFL have over 25 years experience of designing nuclear plant for the whole-fuel
      cycle. In the UK, a Nuclear Decommissioning Authority (NDA) is to be set up to
      ensure that Britain's nuclear legacy is cleaned up safely, securely and cost
      effectively. The resulting challenges and opportunities for shielding design will
      be substantial as the shielding design process was originally devised for the
      design of new plants. Although its underlying principles are equally applicable
      to decommissioning and remediation of old plants, there are many aspects of
      detailed application that need to adapt to this radically different operating
      environment. The paper describes both the common issues and the different
      challenges of shielding design at different operational phases. Sample
      applications will be presented of both new plant and decommissioning projects
      that illustrate not only the robust nature of the processes being used, but also
      how they lead to cost-effective solutions making a substantive and appropriate
      contribution to radiological protection goals.

PMID- 16604701
TI  - Concrete waterproofing in nuclear industry.
AB  - One of the main points of aggregate safety during the transportation and storage
      of radioactive materials is to supply waterproofing for all constructions having
      direct contact with radiating substances and providing strength, seismic
      shielding etc. This is the problem with all waterside structures in nuclear
      industry and concrete installations in the treatment and storage of radioactive
      materials. In this connection, the problem of developing efficient techniques
      both for the repair of operating constructions and the waterproofing of new
      objects of the specified assignment is genuine. Various techniques of concrete
      waterproofing are widely applied in the world today. However, in conditions of
      radiation many of these techniques can bring not a profit but irreparable damage
      of durability and reliability of a concrete construction; for instance, when
      waterproofing materials contain organic constituents, polymers etc. Application
      of new technology or materials in basic construction elements requires in-depth
      analysis and thorough testing. The price of an error might be very large. A
      comparative analysis shows that one of the most promising types of waterproofing
      materials for radiation loaded concrete constructions is "integral capillary
      systems" (ICS). The tests on radiation, thermal and strength stability of ICS and
      ICS-treated concrete samples were initiated and fulfilled in RFNC-VNIITF. The
      main result is--ICS applying is increasing of waterproofing and strength
      properties of concrete in conditions of readiation The paper is devoted to
      describing the research strategy, the tests and their results and also to
      planning of new tests.

PMID- 16604702
TI  - Modelling of radiation field around spent fuel container.
AB  - Operation of nuclear reactors leads to the production of spent nuclear fuel
      (SNF). There are two basic strategies of SNF management: ultimate disposal of SNF
      in geological formations and recycle or repeated utilisation of reprocessed SNF.
      In both options, there is an urgent necessity to study radiation properties of
      SNF. Information about SNF radiation properties is required at all stages of SNF
      management. In order to reach more effective utilisation of nuclear materials,
      new fuel cycles are under development based on uranium-plutonium, uranium-thorium
      and some other types of nuclear fuel. These promising types of nuclear fuel are
      characterised by quite different radiation properties at all the stages of
      nuclear fuel cycle (NFC) listed above. So, comparative analysis is required for
      radiation properties of different nuclear fuel types at different NFC stages. The
      results presented here were obtained from the numerical analysis of the radiation
      field around transport containers of different SNF types and in SNF storage. The
      calculations are carried out with the application of the computer code packages
      SCALE-4.3 and MCNP-4C. Comparison of the dose parameters obtained for different
      models of the transport container with experimental data allowed us to make
      certain conclusions about the errors of numerical results caused by the
      approximate geometrical description of the transport container.

PMID- 16604703
TI  - Neutron cross section measurements at ORELA for improved nuclear data and their
      application.
AB  - To support the Nuclear Criticality Safety Program, the Oak Ridge Electron Linear
      Accelerator (ORELA) has been used to measure the total and capture neutron cross
      sections of several nuclides in the energy range from 100 eV to -600 keV.
      Concerns about the use of existing cross section data in nuclear criticality
      calculations have been a prime motivator for the new cross-section measurements.
      Our new capture cross sections of aluminium, silicon, chlorine, fluorine and
      potassium in the energy range from 100 eV to 600 keV are substantially different
      from the cross sections in evaluated nuclear data files of ENDF/B-VI and JENDL
      3.2.

PMID- 16604704
TI  - Development of a quantum molecular dynamic (QMD) model to describe fission and
      fragment production.
AB  - In this paper is presented the development of a QMD model for the description of
      the spallation reaction at energies from a few MeV to a few hundred MeV. The QMD
      model is developed using a new evaporation-fission model, the generalised
      evaporation model (GEM2). The spectrum of particles and residual nuclide mass and
      charge distributions in reactions of protons and neutrons with heavy targets
      (238U, 208Pb, 207Pb and 2206Pb) has been calculated using the QMD+GEM2 model.

PMID- 16604705
TI  - Theoretical simulation of residual nuclide products in 208,207,206Pb, NATPb and
      209Bi (P,X) reactions at intermediate and high energies.
AB  - The independent and cumulative measured yields of residual products in thin lead
      and bismuth targets irradiated with 0.04-2.6 GeV protons are compared with
      results by the LAHET, CEM03, LAQGSM03, INCL+ABLA, CASCADE and YIELDX codes, in
      order to evaluate the predictive power of the codes in this energy region. We
      found that the predictive power of the tested codes is different but is
      satisfactory for most of the nuclides in the spallation region, though none of
      the codes agree well with the data in the whole-mass region of product nuclides
      and all should be improved further. On the whole, the predictive power of all
      codes for the data in the fission and fragmentation product regions and,
      especially, at the borders between spallation and fission and between fission and
      fragmentation regions is much worse than in the spallation region; therefore,
      development of better evaporation/fission/fragmentation models is of first
      priority.

PMID- 16604706
TI  - A system for the calculation and visualisation of radiation field for maintenance
      support in nuclear power plants.
AB  - A system has been developed to improve the efficiency of maintenance work while
      decreasing the radiation exposure of maintenance personnel in nuclear power
      plants. The input data for dose rate calculation are automatically generated by
      using computer-aided design data. Changes for the input data corresponding to the
      progress of maintenance work, such as installation of a radiation shield and
      removal of a component, are easily input interactively on a graphical user
      interface (GUI). A new method was proposed which searches the sets of source and
      detector points between which gamma-ray attenuation is changed by the component
      movement. The calculation is performed only for the changed sets, so that the
      change of the three-dimensional dose rate distribution is calculated rapidly
      according to the work progress. The dose rate distribution and the radiation
      exposure of maintenance personnel are displayed three-dimensionally in colour
      with plant components and pipes on the GUI.

PMID- 16604707
TI  - GENII-LIN: a new object-oriented interface for the GENII code.
AB  - GENII-LIN is a new object-oriented interface for GENII, a well-known analysis
      tool for the health impact evaluation of accidental or chronic release of
      radionuclides to the environment. GENII-LIN has been developed under the Linux
      OS, chosen because it is a stable, reliable and open source. The suite codes that
      constitute the original GENII simulation kernel have been re-implemented and
      built, using the G77, the Fortran 77 module of the GCC collection. The code
      modules and the flow of data among them are at present fully controlled by a
      management interface written in C++, which is the core of the package. GENII-LIN
      comes with a new graphical user interface (GUI), built using the QT libraries by
      Trolltech. Through the wizard-like GUI, the user has full control over the code
      and can easily handle both the input and the output files.

PMID- 16604708
TI  - Radiopharmaceuticals for targeted radiotherapy.
AB  - This work intends to find specific radiopharmaceuticals for cancer therapy based
      on beta (153Sm and 166Ho) or Auger (99Tc(m)) emitter radionuclides, using cyclic
      and acyclic polyamines as bifunctional chelators. These chelators are designed to
      allow the binding of a tumour seeking biomolecule and/or a DNA intercalator. The
      cyclic amines, such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid,
      1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid and 1,4,7,10
      tetraazacyclotridecane-1,4,7,10-tetraacetic acid, were radiolabelled with 153Sm
      and 166Ho. The radiochemical and biological behaviour of the resulting complexes
      were evaluated in order to assess their potential as building blocks for the
      attachment of selected biomolecules, with the aim of further applying them for
      the development of specific therapeutic radiopharmaceuticals. Novel
      pyrazolyldiamines, bearing a DNA intercalating anthracenyl fragment, were also
      explored to synthesize radioactive complexes with the fac-[99Tc(m)(CO)]3]+
      moiety. The identity of these 99Tc(m) tricarbonyl complexes was confirmed by high
      performance liquid chromatography comparison with rhenium congeners fully
      characterized. By including a DNA intercalator into the chelator framework, we
      expect to induce more efficient and selective damage to the DNA of cancer cells
      by the action of the short-range Auger electrons emitted by 99Tc(m).

PMID- 16604709
TI  - Preliminary design of a Gd-NCT neutron beam based on compact D-T neutron source.
AB  - Gadolinium has been recently proposed, as neutron capture agent in NCT (Neutron
      Capture Therapy), due to both the nuclide high neutron capture cross section, and
      the remarkable selective uptake inside tumour tissue that Gd-loaded compounds,
      can provide. When a neutron external source is supplied, different Gd nuclear
      reactions, and the generated Auger electrons in particular, cause a high local
      energy deposition, which results in a tumour cell inactivation. Preliminary micro
      as well as macrodosimetric Monte Carlo computational investigations show that
      the tumour-to-healthy tissue biological damage ratio is in close relation to the
      neutron beam energy spectrum. The results points out that the optimum neutron
      spectrum, to be used for Gd-NCT, seems to lie in the 1 to 10 keV energy range. In
      order to 'tailor' such spectra, an original, accelerator-driven, neutron source
      and spectrum shaping assembly for hospital-based Gd-NCT are presented and
      preliminary results are reported.

PMID- 16604710
TI  - Neutron and photon fields in the BNCT room with closed beam shutters.
AB  - The epithermal neutron beam at the LVR-15 reactor was designed for the Boron
      Neutron Capture Therapy (BNCT) of cancers, but it has also been used for material
      testing. In the case where the beam is closed with two designed shutters, there
      is still an indispensable background in the irradiation room, which limits the
      movement of persons during patient positioning before exposure or during the
      preparation of the samples. Because the epithermal filter of the beam was
      designed in a former thermal column, as a multi-layer system, it was suspected
      that both fast neutrons and photons penetrated the filter shielding into the
      room. The purpose of this study was to determine the causes of potential faulty
      shielding and to estimate the doses to persons who perform the irradiation
      experiments and/or exposure of patients. The quality of the shielding was
      evaluated from two-dimensional measurements of both neutron and photon
      distribution on the surface of the beam shutter. During the measurement both the
      shutters of the epithermal beam were closed and the reactor was operated at the
      nominal power of 9 MW. This experimental arrangement is similar to the conditions
      that exist when either the irradiation experiments or the exposure of patients is
      performed in this room. The neutron space distribution was measured using a
      Bonner sphere of phi 76.2 mm diameter with an LiI(TI) scintillation detector of
      phi 4 x 8 mm. A small Geiger-Muller tube was used for the measurement of photon
      distribution. The detectors were placed on a three-dimensional positioning
      equipment controlled by a computer, which enabled automatic measurement with 1 cm
      mesh step. Results of the measurement show that the background profile in the
      irradiation room has reasonable maximum only at the beam aperture.

PMID- 16604711
TI  - Effective dose evaluation for chest and abdomen X-ray tests.
AB  - The radiation doses resulting from diagnostic X-ray examinations are routinely
      measured in terms of entrance skin exposure (ESE). In this study, for the purpose
      of radiation protection, the radiation doses received from chest and abdomen X
      ray tests were evaluated in terms of equivalent dose and effective dose. The dose
      calculations were conducted by using the MCNP Monte Carlo code and an adult
      hermaphrodite mathematical phantom. The effects of both operating high voltage
      and projection geometry on the effective dose were investigated. The absolute
      values of the effective doses may be provided from the national average ESE.

PMID- 16604712
TI  - A comparative study of computer assisted assessment of image quality index for
      mammographic phantom images.
AB  - Mammographic phantom images are usually used to study the quality of images
      obtained by dedicated mammographic equipment. The digital image treatment
      techniques allow us to carry out an automatic analysis of the phantom image. In
      this work, some techniques of digital image processing are applied to compute a
      specific image quality index (IQI) for a mammographic phantom, namely CIRS model
      11A version SP01. The algorithm designed analyses the phantom image by means of
      automatic detection of the number of microcalcifications, and the image
      resolution as the number of line pairs per millimetre. Then, the IQI is
      calculated from a scoring system. The manner in which the functioning conditions
      (kV and mAs) of the mammographic equipment and the preprocessing denoising method
      of the digital image affect the results for the IQI are also studied.

PMID- 16604713
TI  - Results of radiation protection programmes on mammography.
AB  - In this paper, we present the results of mammography quality control tests
      related to the work with Portuguese mammography equipment, either in conventional
      or in digital mammography computed radiography, showing the main differences in
      the tested equipments. Quality control in mammography is a very special area of
      quality control in radiology, which demands relatively high knowledge on physics.
      Digital imaging is changing the standards of the radiographic imaging. Regarding
      mammography, this is yet a controversial issue owing to some limitations of the
      digital detectors, like the resolution for instance. A complete set of results
      regarding radiation protection of the patients submitted to mammography diagnosis
      is presented. A discussion of the quality image parameters and its interpretation
      in conventional and digital mammography is presented. In conclusion, we present a
      sample of results that can be considered as characteristics of mammography
      equipment in Portugal.

PMID- 16604714
TI  - Assessment of mammography spectra using compton spectrometry techniques.
AB  - The quality control of mammography units is necessary to reduce the dose imparted
      to women as much as possible. An accurate characterisation of the primary X-ray
      spectra is very useful for this purpose. Primary spectra can be obtained using
      Compton spectrometry techniques. In this work, a commercial spectrometer used to
      characterise a mammography X-ray tube has been simulated using the Monte Carlo
      method by means of the MCNP code. Using the developed model, a Response matrix is
      obtained. Owing to the fact that this matrix is ill-conditioned, the inversion is
      not a simple process. This problem has been solved using the truncated singular
      value decomposition method. Results obtained when this methodology was applied
      have been compared with theoretical X-ray spectra.

PMID- 16604715
TI  - Dosimetric comparison of Monte Carlo codes (EGS4, MCNP, MCNPX) considering
      external and internal exposures of the Zubal phantom to electron and photon
      sources.
AB  - This paper aims at comparing dosimetric assessments performed with three Monte
      Carlo codes: EGS4, MCNP4c2 and MCNPX2.5e, using a realistic voxel phantom, namely
      the Zubal phantom, in two configurations of exposure. The first one deals with an
      external irradiation corresponding to the example of a radiological accident. The
      results are obtained using the EGS4 and the MCNP4c2 codes and expressed in terms
      of the mean absorbed dose (in Gy per source particle) for brain, lungs, liver and
      spleen. The second one deals with an internal exposure corresponding to the
      treatment of a medullary thyroid cancer by 131I-labelled radiopharmaceutical. The
      results are obtained by EGS4 and MCNPX2.5e and compared in terms of S-values
      (expressed in mGy per kBq and per hour) for liver, kidney, whole body and
      thyroid. The results of these two studies are presented and differences between
      the codes are analysed and discussed.

PMID- 16604716
TI  - Study of fragment yields, fission and neutron production in lead targets induced
      by intermediate energy protons.
AB  - A review of the experiments on neutron production in thin and thick lead targets
      and those involving fission reactions and nuclear fragment emission from various
      targets performed with proton beams from the Dubna synchrophasotron is given. Two
      different experimental methods, TOF and SSNTD, were used in the measurements. A
      dependence of the results on proton energy and target type is discussed.

PMID- 16604717
TI  - Comparison between calculation and measured data on secondary neutron energy
      spectra by heavy ion reactions from different thick targets.
AB  - Measured neutron energy fluences from high-energy heavy ion reactions through
      targets several centimeters to several hundred centimeters thick were compared
      with calculations made using the recently developed general-purpose particle and
      heavy ion transport code system (PHITS). It was confirmed that the PHITS
      represented neutron production by heavy ion reactions and neutron transport in
      thick shielding with good overall accuracy.

PMID- 16604718
TI  - Analysis of induced radionuclides in low-activation concrete (limestone concrete)
      using the 12 GeV proton synchrotron accelerator facility at KEK.
AB  - 22Na is one of the long-lived radionuclides induced in shielding concrete of a
      beam-line tunnel of a high-energy particle accelerator facility and poses a
      problem of radiation wastes at the decommissioning of the facility. In order to
      estimate the 22Na concentration induced in shielding concrete, chemical reagents
      such as NaHCO3, MgO, Al203, SiO2 and CaCO3 were irradiated at several locations
      in the beam-line tunnel of the 12 GeV proton synchrotron accelerator at KEK, and
      the 22Na concentrations induced in those chemical reagents were measured. Low
      activation concrete made up of limestone aggregates was also irradiated by
      secondary particles in the beam-line tunnel and the long-lived radionuclide, such
      as 22Na, concentrations induced in the concrete were measured. It was confirmed
      that 22Na concentrations induced in Mg, Al, Si and Ca were lower than that in Na,
      and that 22Na concentrations induced in the low-activation concrete was lower
      than those induced in ordinary concrete made up of sandstone aggregates.

PMID- 16604719
TI  - Angular distribution measurements of photo-neutron yields produced by 2.0 GeV
      electrons incident on thick targets.
AB  - A study of differential photo-neutron yields by irradiation with 2 GeV electrons
      has been carried out. In this extension of a previous study in which measurements
      were made at an angle of 90 degrees relative to incident electrons, the
      differential photo-neutron yield was obtained at two other angles, 48 degrees and
      140 degrees, to study its angular characteristics. Photo-neutron spectra were
      measured using a pulsed beam time-of-flight method and a BC418 plastic
      scintillator. The reliable range of neutron energy measurement was 8-250 MeV. The
      neutron spectra were measured for 10 Xo-thick Cu, Sn, W and Pb targets. The
      angular distribution characteristics, together with the previous results for 90
      degrees, are presented in the study. The experimental results are compared with
      Monte Carlo calculation results. The yields predicted by MCNPX 2.5 tend to
      underestimate the measured ones. The same trend holds for the comparison results
      using the EGS4 and PICA3 codes.

PMID- 16604720
TI  - Comparison of synchrotron radiation calculations between analytical codes (STAC8,
      photon) and Monte Carlo codes (FLUKA, EGS4).
AB  - STAC8 is a significant improvement upon its predecessor PHOTON and is a valuable
      analytical code for quick and conservative beamline shielding designs for
      synchrotron radiation (SR) facilities. In order to check the applicability,
      accuracy and limitations of STAC8, studies were conducted to compare the results
      of STAC8 with those of PHOTON with calculations using the FLUKA and EGS4 Monte
      Carlo codes. Doses and spectra for scattered SR in a few beam-target-shield
      geometries were calculated, with and without photon linear polarisation effects.
      Areas for expanding the STAC8 capabilities, for example, features of the mirror
      reflected lights and double-Compton light calculations and the use of
      monochromatic light have been identified. Some of these features have been
      implemented and benchmarked against Monte Carlo calculations. Reasonable
      agreements were found between the STAC8 and Monte Carlo calculations.

PMID- 16604721
TI  - Neutron analysis of spent fuel storage installation using parallel computing and
      advance discrete ordinates and Monte Carlo techniques.
AB  - In the United States, the Nuclear Waste Policy Act of 1982 mandated centralised
      storage of spent nuclear fuel by 1988. However, the Yucca Mountain project is
      currently scheduled to start accepting spent nuclear fuel in 2010. Since many
      nuclear power plants were only designed for -10 y of spent fuel pool storage, >
      35 plants have been forced into alternate means of spent fuel storage. In order
      to continue operation and make room in spent fuel pools, nuclear generators are
      turning towards independent spent fuel storage installations (ISFSIs). Typical
      vertical concrete ISFSIs are -6.1 m high and 3.3 m in diameter. The inherently
      large system, and the presence of thick concrete shields result in difficulties
      for both Monte Carlo (MC) and discrete ordinates (SN) calculations. MC
      calculations require significant variance reduction and multiple runs to obtain a
      detailed dose distribution. SN models need a large number of spatial meshes to
      accurately model the geometry and high quadrature orders to reduce ray effects,
      therefore, requiring significant amounts of computer memory and time. The use of
      various differencing schemes is needed to account for radial heterogeneity in
      material cross sections and densities. Two P3, S12, discrete ordinate, PENTRAN
      (parallel environment neutral-particle TRANsport) models were analysed and
      different MC models compared. A multigroup MCNP model was developed for direct
      comparison to the SN models. The biased A3MCNP (automated adjoint accelerated
      MCNP) and unbiased (MCNP) continuous energy MC models were developed to assess
      the adequacy of the CASK multigroup (22 neutron, 18 gamma) cross sections. The
      PENTRAN SN results are in close agreement (5%) with the multigroup MC results;
      however, they differ by -20-30% from the continuous-energy MC predictions. This
      large difference can be attributed to the expected difference between multigroup
      and continuous energy cross sections, and the fact that the CASK library is based
      on the old ENDF/B-II library. Both MC and SN calculations were run in parallel on
      a BEOWULF PC-cluster (eight processors). Timing results indicate that the SN
      calculation yielded a detailed dose distribution at over 318,426 points in -164
      h. Unbiased continuous energy MC required 214 h to calculate dose rates with a 1%
      relative error in only 18 regions on the surface of the cask. The biased A3MCNP
      calculations yields dose rates with -0.8% relative error in only 2.5 h on one
      processor. This study demonstrates that a parallel code, such as the 3-D parallel
      SN transport code, PENTRAN can solve a complex large problem, such as the storage
      cask, accurately and efficiently. Moreover, this calculation was performed on a
      relatively inexpensive PC-cluster. Possible inadequacies of the CASK cross
      section library still need to be evaluated.

PMID- 16604722
TI  - Comparison of measured and calculated dose rates for the Castor HAW 20/28 CG.
AB  - In January 2003 neutron and gamma dose rate measurements at a CASTOR HAW 20/28 CG
      were performed by the Bundesamt fur Strahlenschutz at Gorleben. First, commercial
      dose rate measurement devices were used, then spectral measurements with a Bonner
      sphere system were made to verify the results. Axial and circumferential dose
      rate profiles were measured near the cask surface and spectral measurements were
      performed for some locations. A shielding analysis of the cask was performed with
      the MCNP Monte Carlo Code with ENDF/B-VI cross section libraries. The cask was
      modelled 'as built', i.e. with its real inventory, dimensions and material
      densities and with the same configuration and position as in the storage
      facility. The average C/E-ratios are 1.3 for neutron dose rates and 1.4 for gamma
      dose rates. Both the measured and calculated dose rates show the same qualitative
      trends in the axial and circumferential direction. The spectral measurements show
      a variation in the spectra across the cask surface. This correlates with the
      variation found in the C/E-ratios. At cask midheight good agreement between the
      Bonner sphere system and the commercial device (LB 6411) is found with a 7% lower
      derived H*(10) dose rate from the Bonner sphere system.

PMID- 16604723
TI  - Fuzzy-probabilistic model for risk assessment of radioactive material railway
      transportation.
AB  - Transportation of radioactive materials is obviously accompanied by a certain
      risk. A model for risk assessment of emergency situations and terrorist attacks
      may be useful for choosing possible routes and for comparing the various defence
      strategies. In particular, risk assessment is crucial for safe transportation of
      excess weapons-grade plutonium arising from the removal of plutonium from
      military employment. A fuzzy-probabilistic model for risk assessment of railway
      transportation has been developed taking into account the different natures of
      risk-affecting parameters (probabilistic and not probabilistic but fuzzy). Fuzzy
      set theory methods as well as standard methods of probability theory have been
      used for quantitative risk assessment. Information-preserving transformations are
      applied to realise the correct aggregation of probabilistic and fuzzy parameters.
      Estimations have also been made of the inhalation doses resulting from possible
      accidents during plutonium transportation. The obtained data show the scale of
      possible consequences that may arise from plutonium transportation accidents.

PMID- 16604724
TI  - Transmutation of actinides in power reactors.
AB  - Power reactors can be used for partial short-term transmutation of radwaste. This
      transmutation is beneficial in terms of subsequent storage conditions for spent
      fuel in long-term storage facilities. CANDU-type reactors can transmute the main
      minor actinides from two or three reactors of the VVER-1000 type. A VVER-1000
      type reactor can operate in a self-service mode with transmutation of its own
      actinides.

PMID- 16604725
TI  - Characterizing warfare in red teaming.
AB  - Red teaming is the process of studying a problem by anticipating adversary
      behaviors. When done in simulations, the behavior space is divided into two
      groups; one controlled by the red team which represents the set of adversary
      behaviors or bad guys, while the other is controlled by the blue team which
      represents the set of defenders or good guys. Through red teaming, analysts can
      learn about the future by forward prediction of scenarios. More recently, defense
      has been looking at evolutionary computation methods in red teaming. The fitness
      function in these systems is highly stochastic, where a single configuration can
      result in multiple different outcomes. Operational, tactical and strategic
      decisions can be made based on the findings of the evolutionary method in use.
      Therefore, there is an urgent need for understanding the nature of these problems
      and the role of the stochastic fitness to gain insight into the possible
      performance of different methods. This paper presents a first attempt at
      characterizing the search space difficulties in red teaming to shed light on the
      expected performance of the evolutionary method in stochastic environments.

PMID- 16604726
TI  - Findings of scientific misconduct.

PMID- 16604727
TI  - Contraception counts: ranking state efforts.
AB  - (1) California ranks first among states in efforts to help women avoid unintended
      pregnancy, followed by Alaska, South Carolina, Alabama and New York. (2) The
      states that rank the lowest are Nebraska, North Dakota, Indiana, Ohio and Utah.
      (3) The states that made the most progress between 1994 and 2001 are Alaska,
      Louisiana, South Carolina, Oregon and California.

PMID- 16604728
TI  - Eplerenone: new drug. Recent myocardial infarction with heart failure: a
      spironolactone me too.
AB  - (1) Heart failure is diagnosed on the basis of both clinical symptoms and
      evaluation of cardiac function (preferably measured by echocardiography). Left
      ventricular dysfunction is defined as a left ventricular ejection fraction (LVEF)
      below 40%. The drugs of choice for chronic heart failure are certain angiotensin
      converting-enzyme (ACE) inhibitors, some diuretics, some betablockers, and
      spironolactone. In one trial, spironolactone greatly reduced mortality at 24
      months (35%, compared with 46% on placebo, p <0.001). (2) Eplerenone, a
      spironolactone derivative, is marketed for the treatment of left ventricular
      dysfunction in heart failure patients with recent myocardial infarction. (3) The
      EPHESUS study, a double-blind, placebo-controlled trial involving 6632 patients,
      showed a significant reduction in the overall mortality rate among patients with
      heart failure and recent myocardial infarction treated with eplerenone for 16
      months (16.7% versus 14.4%; p = 0.008). This improvement was mainly due to a
      reduction in mortality during the first month of treatment. Eplerenone has not
      been compared with spironolactone, although the latter was known to be effective
      before the EPHESUS trial was conducted. (4) Severe hyperkalemia is frequent with
      eplerenone, occurring in 5.5% of patients. The risk of hyperkalaemia increases
      with renal failure and co-administration of potassium-sparing diuretics, ACE
      inhibitors, angiotensin II receptor antagonists and nonsteroidal antiinflammatory
      drugs. (5) In the short term, the incidence of gynecomastia in patients taking
      eplerenone seems to be low. (6) In patients who develop heart failure after
      myocardial infarction, an indirect comparison of available data favours
      spironolactone over eplerenone (better efficacy, lower risk of hyperkalemia). (7)
      In France, treatment with eplerenone is about 9 times more expensive than
      spironolactone. (8) Spironolactone remains the treatment of choice for patients
      with heart failure and incapacitating dyspnea despite ACE inhibitor and diuretic
      therapy. Eplerenone may possibly be useful for patients who have non severe heart
      failure after recent myocardial infarction.

PMID- 16604729
TI  - Ethinylestradiol + etonogestrel contraceptive vaginal ring: new drug. Possibly
      useful in some situations.
AB  - (1) The standard hormonal contraception consists of a combined oral contraceptive
      containing about 30 micrograms of ethinylestradiol and a well-evaluated and
      widely used progestin such as levonorgestrel or norethisterone. (2) A vaginal
      ring delivering about 120 micrograms of etonogestrel and 15 micrograms of
      ethinylestradiol daily for 3 consecutive weeks per cycle, which is then removed
      for one week, is now marketed in France as a contraceptive. Etonogestrel, a
      desogestrel metabolite, is classified as a 'third-generation' progestin. (3) On
      the basis of 2 non-comparative trials involving a total of 2322 women, the
      vaginal ring's contraceptive efficacy, as measured by the Pearl index, is about 1
      per 100 woman-years, a value similar to that of other available combined hormonal
      contraceptives. (4) In total, 41% and 29.6% of women withdrew early from each of
      the two trials. In the two trials combined, 15.6% of women withdrew due to
      adverse events. (5) A comparative trial versus oral ethinylestradiol +
      levonorgestrel showed no difference in adherence rates, and similar Pearl index
      scores. (6) The most frequent adverse effects, occurring in about 20% of women
      using the vaginal ring, were gynecological disorders (vaginitis, leukorrhea or
      local discomfort). The other adverse effects were those common to all hormonal
      contraceptives. (7) The thromboembolic risk of etonogestrel, when administered in
      a contraceptive ring, has not been evaluated. (8) In practice, the standard
      hormonal contraceptive remains a combined oral contraceptive containing about 30
      micrograms of ethinylestradiol plus a well-evaluated progestin such as
      levonorgestrel or norethisterone. The vaginal ring offers no advantage in terms
      of efficacy, adverse effects or adherence. However, it is an additional effective
      contraceptive and may be preferred by some women, at least temporarily, in
      certain situations.

PMID- 16604730
TI  - Latin America's abortion battles: advocates for women's rights sense progress in
      the ongoing battle for better reproductive health care services.

PMID- 16604731
TI  - Giving women room to exhale: listening to women who have had abortions.

PMID- 16604732
TI  - Prescriptions denied: pharmacy clauses have become the latest battleground in the
      provision of safe and legal medical services.

PMID- 16604733
TI  - Respecting women's rights and fetal value: reflections on the question of fetal
      anesthesia.

PMID- 16604734
TI  - An inconceivable argument: does a law ensuring equal access to prescription drugs
      mean that the Catholic hierarchy will become morally complicit in "immoral acts"?

PMID- 16604735
TI  - The plaintiff as person: cause lawyering, human subject research, and the secret
      agent problem.

PMID- 16604737
TI  - [Patient information. Inactive HBV-carrier].

PMID- 16604736
TI  - Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe
      hepatitis.
AB  - (1) When patients with Parkinson's disease who are taking levodopa develop motor
      fluctuations that do not respond to dose adjustments, the standard treatment is
      the addition of bromocriptine, a dopaminergic agonist. Evaluation of entacapone
      fails to show whether the risk-benefit balance of this catechol-O
      methyltransferase (COMT) inhibitor is at least as favourable as that of
      bromocriptine. (2) Tolcapone, another COMT inhibitor, is back on the French
      market after being withdrawn because of serious hepatic effects. The summary of
      product characteristics (SPC) specifies that tolcapone must only be used when
      entacapone treatment fails or is poorly tolerated. (3) Renewal of marketing
      authorisation was based on one clinical trial in which about half the patients
      were probably not resistant to entacapone. No difference in efficacy was found
      between tolcapone and entacapone. There is no firm evidence that tolcapone is
      effective in a significant number of patients in whom entacapone fails. (4)
      Placebo-controlled trials show that first-line treatment with tolcapone 100 mg to
      200 mg 3 times a day reduces the duration of motor freezing ("off") periods, but
      the global impact of tolcapone on parkinsonism appears to be limited. (5)
      Unblinded randomised controlled trials have failed to show that tolcapone is more
      effective than bromocriptine or pergolide. There are no trials assessing the use
      of tolcapone in combination with dopamine agonists. (6) Adverse effects were
      frequent during clinical trials. They were mainly neurological and
      gastrointestinal, and differed from those associated with bromocriptine. In 1988,
      shortly after worldwide marketing of tolcapone, 3 cases of fatal fulminant
      hepatitis were reported among about 60 000 patients who had taken this drug. Some
      countries, including European Union member states, withdrew marketing
      authorisation. Other countries, including the United States, left tolcapone on
      the market but required stringent monitoring of liver function. Due to a lack of
      transparency on the part of both the manufacturer and the health authorities, we
      do not know if these measures reduced the risk of severe hepatitis. In the trial
      versus entacapone, one of the 75 patients treated with tolcapone 300 mg/day had
      an abnormal increase in serum transaminase activity. (7) In practice, tolcapone
      has a negative risk-benefit balance.

PMID- 16604738
TI  - Porfimer: new drug. Endobrachyesophagus: encouraging preliminary results.
AB  - (1) Patients with endobrachyesophagus (Barrett's oesophagus) and high-grade
      dysplasia are at high risk of developing adenocarcinoma within 3 to 7 years.
      Esophagectomy carries a risk of major morbidity and mortality. Local treatments
      (photocoagulation and endoscopic mucosectomy) are currently under evaluation. (2)
      Marketing authorisation has been granted for a photodynamic treatment based on
      intravenous porfimer injection and laser illumination of the lesion. (3) In a
      randomised trial comparing porfimer photodynamic therapy plus omeprazole with
      omeprazole alone, 208 patients were monitored for at least 2 years. There was no
      difference in mortality between the groups. Thirteen percent of patients on
      combination treatment developed adenocarcinoma (stage not specified), compared to
      29% of patients treated with omeprazole alone (p = 0.006). Nearly half the
      patients had symptoms of photosensitization, and 38% had oesophageal contraction
      requiring at least 1 dilation session. (4) In practice, despite some encouraging
      results, we do not know if photodynamic therapy based on porfimer reduces the
      long-term risk of recurrence, invasive carcinoma, or major surgery. However,
      there is a risk of serious adverse effects. Porfimer photodynamic therapy needs
      to be compared with other endoscopic interventions.

PMID- 16604739
TI  - Lindane: serious neurological effects.
AB  - (1) Cutaneous application of lindane carries a risk of systemic adverse effects,
      including serious neurological disorders. Lindane is readily absorbed through the
      skin, especially damaged skin and in children. (2) In practice, lindane has no
      place in the treatment of either lice or scabies.

PMID- 16604740
TI  - [Goya, Fortuny, Van Gogh, Portinari: lead poisoning in painters across three
      centuries].
AB  - Patobiographic data of four brilliant painters who lived in three different
      centuries (Goya [XVIII], Fortuny and Van Gogh [XIX] and Portinari [XX]), were
      examined in search for a suspected lead poisoning. It is concluded that Goya's
      disease and deafness was probably caused by lead poisoning. Fortuny's death was
      probably precipitated by this illness in conjunction with malaria. This diagnosis
      is more problematic in Van Gogh and only a monograph favouring this was found.
      Portinari certainly suffered from lead poisoning and that finally caused his
      death. This source of the possible poisoning could be the high lead content of
      their paintings.

PMID- 16604741
TI  - Adverse effects of amiodarone: even after the end of treatment.
AB  - (1) Amiodarone, an antiarrhythmic agent, carries a risk of potentially serious
      pulmonary, cardiac, hepatic, thyroid, ocular, peripheral neurological and
      cutaneous (photosensitivity) adverse effects. (2) The average plasma elimination
      half-life of amiodarone is about 50 days. (3) In practice, patients receiving
      amiodarone must be carefully monitored, both during treatment and for at least
      three months (up to one year) after treatment is withdrawn.

PMID- 16604742
TI  - Consumer advertising of psychiatric medications biases the public against
      nonpharmacological treatment.
AB  - In the United States, antidepressant medications are heavily promoted through
      direct-to-consumer advertising, which is regulated by the Food and Drug
      Administration (FDA). Advertisements for selective serotonin reuptake inhibitors
      frequently contain information inconsistent with the scientific evidence on the
      treatment of depression with antidepressants. The information presented serves to
      promote the use of antidepressants by biasing the public against
      nonpharmacological treatment of depression. While the FDA enforces regulations
      requiring fair and balanced presentation when comparing one medication to
      another, there appears to be no action taken against pharmaceutical companies
      that distort scientific evidence in order to disparage nonmedical approaches to
      depression.

PMID- 16604743
TI  - Catholic refusals of immunization: such actions are often unjustified.

PMID- 16604744
TI  - Phytotherapy: rarely mentioned spontaneously.
AB  - (1) In a German study, very few patients informed their healthcare providers that
      they were taking St John's wort. (2) St John's wort is an enzyme inducer and can
      therefore accelerate the elimination of many drugs, including vitamin K
      antagonists, hormonal contraceptives and immunosuppressants. This leads to a
      potential loss of efficacy of these drugs when taken in combination with St
      John's wort. On the other hand, there may be a risk of overdose when St John's
      wort is withdrawn. (3) In practice, patients must be carefully questioned about
      all treatments they are taking, including herbal products they do not consider
      worth mentioning.

PMID- 16604745
TI  - Why secular humanism is wrong about assisted suicide.

PMID- 16604746
TI  - The case against euthanasia and physician-assisted suicide.

PMID- 16604747
TI  - The case for physician-assisted suicide.

PMID- 16604748
TI  - Buprenorphine replacement therapy: a confirmed benefit.
AB  - (1) The aim of replacement therapy for heroin addiction is to suppress craving
      for other opiates and to prevent opiate withdrawal symptoms. (2) In France,
      methadone was the first drug to be licensed for this use, in 1995, with very
      strict prescribing and dispensing conditions. Buprenorphine was approved in 1996,
      and was subject to less restrictive conditions. (3) In 2003 in France, an
      estimated 80 000 people were receiving replacement therapy with buprenorphine and
      14 000 with methadone. (4) A meta-analysis of 13 comparative trials involving a
      total of 2544 patients showed that buprenorphine 6 to 12 mg initially reduced
      both opiate and benzodiazepine use, whereas doses of 2 to 4 mg had no marked
      impact on heroin use. This meta-analysis concluded that buprenorphine and
      methadone had similar efficacy in clinical trials in which the dose was adjusted
      to outcome. There were more dropouts with buprenorphine than with methadone. A
      daily dose of 16 mg appeared to be roughly equivalent to 60 mg/day methadone. (5)
      France appears to be the only country to have relied primarily on buprenorphine
      as replacement therapy for heroin addiction. This has been the case in France
      since 1996. The frequency of heroin overdose has fallen markedly in France since
      1996, possibly due in part to the availability of replacement therapies. Overall
      mortality among drug users has also declined, but this is largely due to more
      effective treatment of HIV infection. (6) In France, a two-year cohort study of
      patients treated with buprenorphine and a survey conducted during the first year
      of buprenorphine replacement were funded by the manufacturer, Schering-Plough.
      The results showed that more than two-thirds of patients remained on treatment,
      and that, overall, the patients' general condition improved. (7) Opioid-like
      adverse effects are infrequent under normal conditions of use. There are reports
      of cases of hepatitis in patients taking buprenorphine, with or without a
      benzodiazepine. Attribution to buprenorphine is unclear, however, due to the lack
      of appropriate analyses. (8) Some of the key adverse effects occur during misuse:
      buprenorphine tablets are often injected, especially during the first few months
      of treatment (sometimes for more than two years). Injection carries a risk of
      infections; other potential long-term effects are poorly understood. Compared
      with methadone users, and regardless of the substances involved, buprenorphine
      users appear more likely to self-inject. (9) The consequences of sniffing crushed
      buprenorphine tablets have not been studied. (10) Deaths have been reported
      following buprenorphine overdose, but they appear to be less frequent than with
      methadone (0.2 and 0.7 deaths per 1000 users, respectively in 1998). (11)
      Approaches designed to help patients stop self-injecting have not been tested in
      comparative trials. Prescriptions of methadone syrup or an injection opiate may
      be worth trying when all other measures fail.

PMID- 16604749
TI  - Ethical issues in genetic testing.
AB  - Genetic testing is becoming ever more prevalent in the post-genome project
      practice of medicine. Subsequently, genetic testing for disorders lacking any
      therapeutic interventions is also becoming more prevalent. This article will
      examine some of the ethical challenges raised by our ability to know but not to
      cure.

PMID- 16604750
TI  - Health charities, unethical research and organizational integrity.
AB  - Organizations, particularly Catholic hospitals, schools and social service
      agencies, should re-examine their relationships to health and medical charities
      promoting unethical research such as human embryonic stem cell research and
      therapeutic cloning. Part 6 of the Ethical and Religious Directives provides a
      helpful framework for ethical analysis and action.

PMID- 16604751
TI  - Why the brain is the organ of the future.

PMID- 16604752
TI  - [Asthma, nonspecific bronchial hyperreactivity. Asking knowledgable experts].

PMID- 16604753
TI  - Pediatric asthma and development of atopy.

PMID- 16604754
TI  - Predictive genetic testing of minors.

PMID- 16604755
TI  - Rendering complex scenes for psychophysics using RADIANCE: how accurate can you
      get?
AB  - Rendering packages are used by visual psychophysicists to produce complex stimuli
      for their experiments, tacitly assuming that the simulation results accurately
      reflect the light-surface interactions of a real scene. RADIANCE is a physically
      based, freely available, and commonly used rendering software. We validated the
      calculation accuracy of this package by comparing simulation results with
      measurements from real scenes. RADIANCE recovers color gradients well but the
      results are shifted in color space. Currently, there is no better simulation
      alternative for achieving physical accuracy than by combining a spectral
      rendering method with RADIANCE.

PMID- 16604756
TI  - Impact of Zernike-fit error on simulated high- and low-contrast acuity in
      keratoconus: implications for using Zernike-based corrections.
AB  - This study examines the extent to which a Zernike-based optical correction can
      restore acuity in keratoconus as a function of disease severity and contrast
      level. Increasingly complete Zernike corrections in the presence of Zernike-fit
      error were simulated. Acuity for keratoconic eyes with <60 D maximum corneal
      power reached 20/13 with a fifth-order Zernike correction under high-contrast
      conditions and exhibited a loss of 0.1 logMAR (minimum angle of resolution) (from
      20/32 to 20/40) for low-contrast conditions. Acuity for keratoconic eyes with >60
      D maximum corneal power approached 20/13 with sixth-tenth-order corrections under
      high-contrast conditions but did not return to similar levels with a tenth-order
      correction for low-contrast conditions. The results suggest that fit error
      affects visual performance for more difficult tasks and that restoring high
      contrast acuity (20/16 or better) using a fifth-order Zernike correction is not
      limited by Zernike=fit error for over 88% of keratoconus cases.

PMID- 16604757
TI  - Interocular high-order corneal wavefront aberration symmetry.
AB  - The interocular symmetry of the high-order corneal wavefront aberration (WA) in a
      population of myopic eyes was analyzed before and after photorefractive
      keratectomy (PRK). The preoperative and one-year postoperative corneal aberration
      data (from third to seventh Zernike orders) for 4- and 7-mm pupils from right and
      left eyes were averaged after correcting for the effects of enantiomorphism to
      test for mirror symmetry. Also, the mean corneal point-spread function (PSF) for
      right and left eyes was calculated. Preoperatively, a moderate and high degree of
      correlation in the high-order corneal WA between eyes was found for 4- and 7-mm
      pupils, respectively. Myopic PRK did not significantly change the interocular
      symmetry of corneal high-order aberrations. No discernible differences in the
      orientation PSF between eyes were observed one year after surgery in comparison
      with the preoperative state over the two analyzed pupils.

PMID- 16604758
TI  - Complex source description of focal regions.
AB  - Closed-form solutions of the two-dimensional homogeneous wave equation are
      presented that provide focal-region descriptions corresponding to a converging
      bundle of rays. The solutions do have evanescent wave content and can be
      described as a source-sink pair or particle-antiparticle pair, collocated in
      complex space, with the complex location being critical in the determination of
      beam shape and focal region size. The wave solutions are not plagued by
      singularities, have a finite energy, and have a limitation on how small the focal
      size can get, with a penalty for limiting small spot sizes in the form of
      impractically high associated reactive energy. The electric-field-defined spot
      size limiting value is 0.35lambda x 0.35lambda, which is about 38% of the
      Poynting-vector-defined minimum spot size (0.8lambda x 0.4lambda) and corresponds
      to a condition related to the maximum possible beam angle. A multiple set of
      solutions is introduced, and the elementary solutions are used to produce new
      solutions via superposition, resulting in fields with chiral character or with
      increased depth of focus. We do not claim generality, as the size of focal
      regions exhibited by the closed-form solutions has a lower bound and hence is not
      able to account for Pendry's "ideal lens" scenario.

PMID- 16604759
TI  - Compact laser radar and three-dimensional camera.
AB  - A novel three-dimensional (3D) camera is capable of providing high-precision 3D
      images in real time. The camera uses a diode laser to illuminate the scene, a
      shuttered solid-state charge-coupled device (CCD) sensor, and a simple phase
      detection technique based on the sensor shutter. The amplitude of the reflected
      signal carries the luminance information, while the phase of the signal carries
      range information. The system output is coded as a video signal. This camera
      offers significant advantages over existing technology. The precision in range is
      dependent only on phase shift and laser power and theoretically is far superior
      to existing time-of-flight laser radar systems. Other advantages are reduced size
      and simplicity and compact and inexpensive construction. We built a prototype
      that produced high-resolution images in range the (z) and x-y.

PMID- 16604760
TI  - Aspects of signal-dependent noise characterization.
AB  - An automated method is presented for analyzing signal-dependent noise. Signal
      dependent noise is present in many types of data-acquisition processes and has
      been investigated by other researchers with various methods. Regardless of the
      noise analysis methods, often the starting point is based on a particular signal
      dependent noise model, which also forms the basis for our study. The approach
      determines whether the estimated noise variance is dependent on the signal by
      approximating the functional relation within the constraints of the assumed
      signal-noise model. The method relies on the Fourier attributes of the signal and
      noise and uses the wavelet expansion for separating these components. The
      technique does not rely on the underlying noise and signal probability
      distributions. Two-dimensional simulations as well as mammography data are used
      to illustrate the merits of the approach.

PMID- 16604761
TI  - Optical transfer function of three-dimensional display systems.
AB  - I investigate the optical transfer function of three-dimensional display systems.
      Moreover, I obtain an average sampled modulation transfer function describing
      discrete, sampled display systems and show that in the proper limit of
      geometrical optics it is equivalent to the shift-invariant optical transfer
      function. I apply the theory to describe holographic stereograms and discuss the
      effects of amplitude and phase filters on the optical resolution.

PMID- 16604762
TI  - Incorporating mask topography edge diffraction in photolithography simulations.
AB  - In deep ultraviolet lithography simulations, conventional application of
      Kirchhoff's boundary conditions on the mask surface provides the so-called "thin
      mask" approximation of the object field. Current subwavelength lithographic
      operation, however, places a serious limitation on this approximation, which
      fails to account for the topographical, or "thick-mask," effects. In this paper,
      a new simulation model is proposed that is theoretically founded on the well
      established physical theory of diffraction. This model relies on the key result
      that diffraction effects can be interpreted as an intrinsic edge property, and
      modeled with just two fixed parameters: width and transmission coefficient of a
      locally determined boundary layer applied to each chrome edge. The proposed model
      accurately accounts for thick-mask effects of the fields on the mask, greatly
      improving the accuracy of aerial image simulations in photolithography, while
      maintaining a reasonable computational cost.

PMID- 16604763
TI  - Self-Fourier functions and self-Fourier operators.
AB  - The concept of self-Fourier functions, i.e., functions that equal their Fourier
      transform, is almost always associated with specific functions, the most well
      known being the Gaussian and the Dirac delta comb. We show that there exists an
      infinite number of distinct families of these functions, and we provide an
      algorithm for both generating and characterizing their distinct classes. This
      formalism allows us to show the existence of these families of functions without
      actually evaluating any Fourier or other transform-type integrals, a task often
      challenging and frequently not even possible.

PMID- 16604764
TI  - Coincidence subwavelength fractional Fourier transform.
AB  - The coincidence subwavelength fractional Fourier transforms (FRTs) with entangled
      photon pairs and incoherent light radiation are introduced as an extension of the
      recently introduced coincidence FRT. Optical systems for implementing the
      coincidence subwavelength FRTs are designed. The width of the coincidence
      subwavelength FRT pattern is two times narrower than the width of the coincidence
      FRT. The coincidence subwavelength FRT with partially coherent light radiation is
      also studied numerically. Differences between the coincidence subwavelength FRT
      with entangled photon pairs and that with incoherent light radiation are
      discussed.

PMID- 16604765
TI  - Simulation of two-dimensional Kerr photonic crystals via fast Fourier
      factorization.
AB  - We present an adaptation of the fast Fourier factorization method to the
      simulation of two-dimensional (2D) photonic crystals with a third-order
      nonlinearity. The algorithm and its performance are detailed and illustrated via
      the simulation of a Kerr 2D photonic crystal. A change in the transmission
      spectrum at high intensity is observed. We explain why the change does not reduce
      to a translation (redshift) but rather consists in a deformation and why one side
      of the bandgap is more suited to a switching application than the other one.

PMID- 16604766
TI  - Pulse compression beyond the Fourier-transform limit.
AB  - Theories of a technique for compression of an ultrashort femtosecond laser pulse
      beyond its Fourier-transform limit based on the pulse shaping technique are
      proposed. The technique is called superresolution in time domain (STD). Global
      optimization theories for the design of a mask to modulate the spectrum of an
      input pulse to obtain a STD output pulse are proposed. Several design examples
      illustrate the feasibility of STD. Some fundamental limits of STD are also
      provided.

PMID- 16604767
TI  - Nonparaxial scalar treatment of sinusoidal phase gratings.
AB  - Scalar diffraction theory is frequently considered inadequate for predicting
      diffraction efficiencies for grating applications where lambda/d>0.1. It has also
      been stated that scalar theory imposes energy upon the evanescent diffracted
      orders. These notions, as well as several other common misconceptions, are driven
      more by an unnecessary paraxial approximation in the traditional Fourier
      treatment of scalar diffraction theory than by the scalar limitation. By scaling
      the spatial variables by the wavelength, we have previously shown that diffracted
      radiance is shift invariant in direction cosine space. Thus simple Fourier
      techniques can now be used to predict a variety of wide-angle (nonparaxial)
      diffraction grating effects. These include (1) the redistribution of energy from
      the evanescent orders to the propagating ones, (2) the angular broadening (and
      apparent shifting) of wide-angle diffracted orders, and (3) nonparaxial
      diffraction efficiencies predicted with an accuracy usually thought to require
      rigorous electromagnetic theory.

PMID- 16604768
TI  - Boundaryless finite-difference method for three-dimensional beam propagation.
AB  - A two-dimensional optical field paraxial propagation scheme, in Cartesian and
      cylindrical coordinate systems, is proposed. This is achieved by extending the
      method originally proposed by Ladouceur [Opt. Lett. 21, 4 (1996)] for
      boundaryless beam propagation to two-dimensional optical wave fields. With this
      formulation the arbitrary choice of physical window size is avoided by mapping
      the infinite transverse dimensions into a finite-size domain with an appropriate
      change of variables, thus avoiding the energy loss through the artificial
      physical boundary that is usually required for the absorbing or the transparent
      boundary approach.

PMID- 16604769
TI  - Numerical calculation of a converging vector electromagnetic wave diffracted by
      an aperture by using Borgnis potentials. I. General theory.
AB  - A method is proposed, on the basis of the vector electromagnetic theory, for the
      numerical calculation of the diffraction of a converging electromagnetic wave by
      a circular aperture by using Borgnis potentials as auxiliary functions. The
      diffraction problem of vector electromagnetic fields is simplified greatly by
      solving the scalar Borgnis potentials. The diffractive field is calculated on the
      basis of the boundary integral equation, taking into consideration the
      contribution of the field variables on the diffraction screen surface, which is
      ignored in the Kirchhoff assumption. An example is given to show the
      effectiveness and suitability of this method and the distinctiveness of the
      diffractive fields caused by the vector characteristics of the electromagnetic
      fields.

PMID- 16604770
TI  - Spatially varying optical and acoustic property reconstruction using finite
      element-based photoacoustic tomography.
AB  - A finite-element reconstruction algorithm for simultaneous reconstruction of both
      optical and acoustic properties of heterogeneous media is presented. The
      algorithm is based on the Helmholtz-like photoacoustic wave equation in the
      frequency domain. A dual meshing scheme is described and an adjoint sensitivity
      method is adopted for efficient inverse computation. The algorithm is implemented
      with the second-order absorbing boundary conditions and with a multireceiving and
      multifrequency strategy. The algorithm is evaluated using simulated data under
      various practical cases including different noise levels, varied range of
      receiving frequency, different contrast levels between the heterogeneity and
      background region, and multiple targets. The effect of acoustic heterogeneity on
      conventional pure optical absorption reconstruction is also studied.

PMID- 16604771
TI  - Formulation of correlations for general-type beams in atmospheric turbulence.
AB  - Log-amplitude and phase correlations of general-type beams are formulated in
      atmospheric turbulence. A general beam is described as the superposition of many
      sets of multimode contents, each mode being off-axis Hermite-Gaussian. Since the
      Rytov solution is utilized, the formulas are valid in the weakly turbulent
      regime. The results are presented in integral forms that should be numerically
      evaluated for the specific beam type of interest. Our general beam results
      correctly reduce to the existing solutions for the correlations of limiting-case
      beams such as higher-order single-mode, multimode, off-axis Hermite-Gaussian,
      Hermite-sinusoidal-Gaussian, higher-order-annular, flat-topped-Gaussian, and thus
      naturally fundamental mode, plane, and spherical waves. Scintillation index and
      phase fluctuations in atmospheric optical links employing such special beams will
      be examined in future using the results reported here.

PMID- 16604772
TI  - Colorimetric method for phase evaluation.
AB  - Measurements of very small phase changes in optical measurement techniques are
      usually performed with interferometric methods that are based on evaluation of
      interference patterns, which correspond to a phase change of the investigated
      wave field. If values of the phase change are small, it is difficult to determine
      accurately the phase values, and one needs very expensive measurement systems. We
      present a simple method for evaluation of small phase variations that uses the
      interference of polychromatic light. The phase change affects the color of the
      interference pattern, and the color of the interference pattern corresponds to a
      specific phase change that can be evaluated using colorimetric analysis. We
      describe and analyze our colorimetric phase evaluation method. The proposed
      method offers accurate results, and it may be suitable for practical utilization
      in the optical industry.

PMID- 16604773
TI  - Efficient deconvolution of noisy periodic interference signals.
AB  - The interference signal formed by combining two coherent light beams carries
      information on the path difference between the beams. When the path difference is
      a periodic function of time, as, for example, when one beam is reflected from a
      vibrating surface and the other from a fixed surface, the interference signal is
      periodic with the same period as the vibrating surface. Bessel functions provide
      an elegant and efficient means for deconvoluting such periodic interference
      signals, thus making it possible to obtain the displacement of the moving surface
      with nanometer resolution. Here we describe the mathematical basis for the signal
      deconvolution and employ this technique to obtain the amplitude of miniature
      capillary waves on water as a test case.

PMID- 16604774
TI  - Electromagnetic field computation in semiconductor laser resonators.
AB  - An electromagnetic method based on rigorous diffraction theory of gratings is
      applied to the analysis of fields in semiconductor laser cavities. The method is
      based on the Fourier modal method; it is fully rigorous for infinitely periodic
      resonators and highly accurate for single resonators when absorbing boundary
      conditions are applied. Fundamental-mode intracavity and near-field distributions
      are evaluated for some selected geometries, and resonance frequencies are
      predicted.

PMID- 16604775
TI  - Analysis of eigenfields in the axicon-based Bessel-Gauss resonator by the
      transfer-matrix method.
AB  - The axicon-based-Bessel-Gauss resonator (ABGR) has been proposed for the
      production of Bessel-Gauss beams. To analyze eigenfields of the ABGR with a plane
      or spherical output coupler, we present and demonstrate the transfer-matrix
      method. Since the method is slow to converge to eigenmodes of the ABGR by use of
      the Fox and Li iterative algorithm, in this paper the Huygens-Fresnel diffraction
      integral equations associated with ray matrices are converted into finite-sum
      matrix equations, and mode-fields and corresponding losses are described as
      eigenvectors and eigenvalues of a transfer matrix according to the self
      reproducing principle of the laser field. By solving the transfer matrix for
      eigenvectors and eigenvalues, we obtain field distributions and losses of the
      dominant eigenmodes. Moreover, eigenfields across arbitrary interfaces between
      the axicon and the output coupler, and the propagation of output beams, are
      simulated by using the fast-Fourier transform (FFT). The calculation results
      reveal that because of the ABGR's poor transverse mode discrimination the ABGR
      should be improved to produce good-quality Bessel-Gauss beams.

PMID- 16604776
TI  - Controllable elliptical dark-hollow beams.
AB  - A new (to our knowledge) kind of light beam called the controllable elliptical
      dark-hollow beam (CEDHB), is introduced to describe dark-hollow beams with
      axially rotational asymmetry by using the tensor method. The propagation formulas
      of CEDHBs through paraxial aligned and misaligned nonsymmetrical optical systems
      are derived through vector integration. With the derived formulas, the
      propagation properties of CEDHBs in free-space propagation and through a
      misaligned thin lens are studied graphically. The CEDHBs provide a convenient
      model to describe and treat dark-hollow beams with axially rotational asymmetry
      and can be used conveniently to analyze atoms manipulated with a dark-hollow
      beam.

PMID- 16604777
TI  - Optical path difference in a plane-parallel uniaxial plate.
AB  - The flux of energy given by the Poynting vector Se and the kt-wave vector normal
      to the geometrical wavefront for the extraordinary ray propagating through
      uniaxial crystals can be evaluated by using the theory developed by Avendano
      Alejo et al. [J. Opt. Soc. Am. A 19, 1668 (2002)] and Avendano-Alejo and
      Stavroudis [J. Opt. Soc. Am. A 19, 1674 (2002)]. We give here the equations
      necessary to evaluate the general dispersion angle Se x kt. Additionally we
      define two new dispersion angles, Se x A and kt x A, where A is the crystal axis
      vector. With these new dispersion angles we evaluate the optical path length
      traversed by the extraordinary ray in a plane-parallel uniaxial plate when the
      crystal axis lies in the plane of incidence.

PMID- 16604778
TI  - Joint spatial-directional localization features of wave fields focused at a
      complex point.
AB  - A systematic study of the joint spatial-directional localization features of
      monochromatic wave fields focused at a complex point is presented, on the basis
      of recently introduced measures of spatial and directional spread for wide-angle
      wave fields. Such features are compared with those of a class of fields defined
      to achieve the theoretical minimum product of these spread measures. It is found
      that the two classes of fields are remarkably similar.

PMID- 16604779
TI  - Changes in the spectrum, in the spectral degree of polarization, and in the
      spectral degree of coherence of a partially coherent beam propagating through a
      gradient-index fiber.
AB  - Expressions are derived for the cross-spectral density matrix of an
      electromagnetic Gaussian Schell-model beam propagating through a paraxial ABCD
      system. Using the recently developed unified theory of coherence and polarization
      of electromagnetic beams and the ABCD matrix for gradient-index fibers, we study
      the changes of the spectral density, of the spectral degree of polarization, and
      of the spectral degree of coherence of such a beam as it travels through the
      fiber. Effects of material dispersion are also considered.

PMID- 16604780
TI  - Classification of dispersion equations for homogeneous, dielectric-magnetic,
      uniaxial materials.
AB  - The geometric representation at a fixed frequency of the wave vector (or
      dispersion) surface omega(k) for lossless, homogeneous, dielectric-magnetic
      uniaxial materials is explored for the case when the elements of the relative
      permittivity and permeability tensors of the material can have any sign.
      Electromagnetic plane waves propagating inside the material can exhibit
      dispersion surfaces in the form of ellipsoids of revolution, hyperboloids of one
      sheet, or hyperboloids of two sheets. Furthermore, depending on the relative
      orientation of the optic axis, the intersections of these surfaces with fixed
      planes of propagation can be circles, ellipses, hyperbolas, or straight lines.
      The understanding obtained is used to study the reflection and refraction of
      electromagnetic plane waves due to a planar interface with an isotropic medium.

PMID- 16604781
TI  - Focusing concave lens using photonic crystals with magnetic materials.
AB  - The guided modes lying in the upper gap-edge band in the photonic band structure
      of photonic crystals have negative values of refractive index. This feature
      generates many interesting optical phenomena, and some spectacular photonic
      devices such as focusing slabs have been developed. We report the design of a
      photonic-crystal, planoconcave lens for focusing incident parallel light, and
      theoretically analyze the chromatic aberrations for TM and TE modes. In addition
      to dielectric photonic crystals, the chromatic aberration of a magnetic photonic
      crystal planoconcave lens was investigated because the magnetic permeability may
      also contribute to the periodic index contrast in photonic crystals, especially
      at long wavelengths. A significant difference was found in the chromatic
      aberration for a TM mode propagating in a dielectric than in a magnetic photonic
      crystal planoconcave lens.

PMID- 16604782
TI  - Phase shifts in frustrated total internal reflection and optical tunneling by an
      embedded low-index thin film.
AB  - Simple and explicit expressions for the phase shifts that p- and s-polarized
      light experience in frustrated total internal reflection (FTIR) and optical
      tunneling by an embedded low-index thin film are obtained. The differential phase
      shifts in reflection and transmission deltar, deltat are found to be identical,
      and the associated ellipsometric parameters psir, psit are governed by a simple
      relation, independent of film thickness. When the Fresnel interface reflection
      phase shifts for the p and s polarizations or their average are quarter-wave, the
      corresponding overall reflection phase shifts introduced by the embedded layer
      are also quarter-wave for all values of film thickness. In the limit of zero film
      thickness (i.e., for an ultrathin embedded layer), the reflection phase shifts
      are also quarter-wave independent of polarization (p or s) or angle of incidence
      (except at grazing incidence). Finally, variable-angle FTIR ellipsometry is shown
      to be a sensitive technique for measuring the thickness of thin uniform air gaps
      between transparent bulk media.

PMID- 16604783
TI  - Theory of spectroscopic devices.
AB  - A fundamental formalism featuring the common working principle of different
      spectroscopic devices is introduced. General formulas for angular dispersion,
      free spectral range, and spectral resolution are deduced from both the impulse
      response function and the spatial transmission function of the device, based on
      the assumption that these functions can be written up as the product of a finite
      width, real-aperture function, and a complex periodic function. The method will
      also be shown to work in specific cases.

PMID- 16604786
TI  - [The builder of rural health centers. Interview by Catherine Maisonneuve].

PMID- 16604790
TI  - [The patient's record, contents and rules of good practice].

PMID- 16604791
TI  - [Nursing surveillance during antitubercular drug treatment].

PMID- 16604792
TI  - [Wound healing in a humid milieu].

PMID- 16604793
TI  - [Hydroclean active: an absorbent irrigated dressing for infected wounds!].

PMID- 16604794
TI  - [Conditions for the emergence of a scientific and professional nursing
      discipline].

PMID- 16604795
TI  - [Supportive care in oncology].

PMID- 16604796
TI  - [What is supportive care?].

PMID- 16604797
TI  - [Coordination of external care, an original supportive care component at the
      Gustave Roussy Institute].

PMID- 16604798
TI  - [Nursing care in the supportive care service].

PMID- 16604799
TI  - [Nursing consultation, the central link in supportive care organization].

PMID- 16604800
TI  - [Regional approach in oncology supportive care].

PMID- 16604801
TI  - [A health network for optimal management].

PMID- 16604802
TI  - [Supportive care in oncology. Bibliography].

PMID- 16604803
TI  - [Difficulties in executing supportive care in community health nursing...].

PMID- 16604804
TI  - [2/10 Training in the Eneis study 2004].

PMID- 16604805
TI  - [Analgesic drugs. 1/4. Evaluation and therapeutic management of pain].

PMID- 16604807
TI  - [Arteriopathy and diabetes, some major risks].

PMID- 16604808
TI  - [Arteriopathy in the diabetic, role of the podiatrist].

PMID- 16604809
TI  - [An original educational tool for gestational diabetes].

PMID- 16604810
TI  - [Retinopathy, a major cause of blindness in the adult diabetic].

PMID- 16604811
TI  - [Diabetic retinopathy, nursing care].

PMID- 16604812
TI  - [Insulin in the diabetic heart patient, only the glycemic results count].

PMID- 16604813
TI  - [Education of the diabetic patient after a cardiac event].

PMID- 16604814
TI  - [Renal insufficiency in the diabetic patient, prevention before everything else].

PMID- 16604815
TI  - [Renal insufficiency and diabetes, dietetic management].

PMID- 16604816
TI  - [Coaching patients in compliance].

PMID- 16604817
TI  - [Improving compliance, the psychologist's point of view].

PMID- 16604818
TI  - Safety and tolerability of a 'refrigeration-free' formulation of interferon beta
      1b--results of a double-blind, multicentre, comparative study in patients with
      relapsing-remitting or secondary progressive multiple sclerosis.
AB  - The original glucose-based formulation of Betaferon/Betaseron (interferon beta
      1b) requires refrigerated storage. A refrigeration-free formulation of interferon
      beta-1b, based on mannitol, is stable at room temperature for up to 2 years, and
      offers a greater degree of flexibility for patients with multiple sclerosis (MS).
      We compared the safety and tolerability of the two formulations in a 24-week,
      randomized, double-blind, parallel group, Phase IV clinical study conducted in
      303 patients with MS. Patients received the glucose formulation (IFNbeta-1b-G)
      for 8 weeks, and were then randomized to receive either IFNbeta-1b-G or the
      refrigeration-free formulation (IFNbeta-1b-M) for a further 8 weeks. On
      completion of the double-blind phase, all patients received IFNbeta-1b-M for an 8
      week follow-up period. The primary outcome measure was the proportion of
      injection sites that developed reactions per patient during the double-blind
      period. In addition, a range of secondary outcomes relating to these reactions
      was also assessed. The difference in the proportion of injection-site reactions
      between the two groups was not statistically significant (59% IFNbeta-1b-G versus
      60% IFNbeta-1b-M). There were no statistically significant differences observed
      between the two treatment groups in any of the secondary tolerability endpoints.
      The results from this study demonstrate that the tolerability and safety profiles
      of both formulations are extremely good, and that the refrigeration-free
      formulation of interferon beta-1b is comparable with that of the original glucose
      formulation.

PMID- 16604819
TI  - The significance of carotid artery plaques in the detection of coronary artery
      disease in asymptomatic type 2 diabetic patients.
AB  - This study aimed to evaluate whether there was any association between carotid
      artery ultrasound parameters and the results of stress myocardial single photon
      emission computed tomography (SPECT) and coronarography in 126 asymptomatic type
      2 diabetic patients. Thirty-three (26%) patients had an abnormal SPECT result, 33
      (26%) had an intermediate result and 60 (48%) had a normal result. Carotid
      ultrasound demonstrated a significant association between an abnormal SPECT
      result and the presence of atheroma plaques and reduced distensibility of the
      common carotid artery, but there was no association with intima-media thickness
      (IMT). In 38 diabetic patients who agreed to be examined with selective
      coronarography, significant coronary stenosis (at least one stenosis > or = 70%)
      was diagnosed in 22 (58%) patients. A significant association was demonstrated
      between significant coronary stenosis and the presence of atheroma plaques;
      however, there was no association between stenosis and reduced distensibility of
      the common carotid artery or IMT.

PMID- 16604820
TI  - Electrophysiological abnormalities in type 2 diabetic patients with reduced
      levels of insulin-like growth factor I.
AB  - This cross-sectional study investigated electrophysiological abnormalities in
      type 2 diabetics with normal and reduced insulin-like growth factor I (IGF-I)
      levels. Sixty patients and 20 non-diabetic controls were included in the study.
      The fasting serum glucose was measured and IGF-I levels were determined by
      radioimmunoassay in all patients. Nerve conduction tests were performed in all
      the study participants on the ulnar nerve and lower extremities. Compared with
      the controls, all the patients showed a reduction in the peak amplitude of the
      motor response, 58% showed a reduction in the motor conduction velocity and 55%
      showed a reduction in the sensory conduction velocity. There was no statistically
      significant correlation between the electrophysiological changes and the glucose
      or IGF-I levels. In conclusion, there does not appear to be a correlation between
      serum glucose or IGF-I levels and electrophysiological abnormalities in patients
      with type 2 diabetes mellitus.

PMID- 16604821
TI  - Non-verbal communication method based on a biochemical marker for people with
      severe motor and intellectual disabilities.
AB  - This study evaluated a novel non-verbal communication method for people with
      severe motor and intellectual disabilities (SMID) based on a biochemical marker,
      salivary amylase. The physical and psychological status of 10 people with SMID
      was quantitatively evaluated using a hand-held salivary amylase activity monitor.
      Each patient needed daily gastric and/or bronchial tube exchanges and these
      medical procedures were thought to cause severe distress and pain. Salivary
      amylase activity and heart rate were simultaneously measured during 32 medical
      procedures. The medical procedures resulted in a significant mean increase for
      individuals of 70% in salivary amylase activity. The increase in salivary amylase
      activity was more than four-fold that observed for heart rate. The structural
      equation modelling analysis also demonstrated a significant correlation between
      pain and salivary amylase activity. Our data indicate that salivary amylase
      activity might be used as a non-verbal method of assessing pain in people with
      SMID.

PMID- 16604822
TI  - Evaluation of epoetin alpha (rHuEPO) and darbepoetin alpha (DARB) on human burst
      colony formation (BFU-E) in culture.
AB  - The erythropoietic effect of recombinant human erythropoietin, epoetin alpha
      (rHuEPO), in promoting the growth of erythroid burst-forming units (BFU-E) was
      compared with darbepoetin alpha (DARB), a rHuEPO analogue obtained by site
      directed mutagenesis. Human bone marrow cells derived from healthy donors were
      cultured with different concentrations of rHuEPO or DARB for 12 - 21 days and BFU
      E were counted using an inverted microscope. The EC50 of rHuEPO was about 10-fold
      lower than DARB and the size of the colonies was significantly larger in rHuEPO
      containing cultures using comparable concentrations. The maximum number of
      colonies obtained in some rHuEPO-containing cultures was also higher than for
      DARB. The number of colonies in DARB-containing cultures was increased, in part,
      by the addition of low concentrations of rHuEPO, but not by DARB, even at high
      concentrations. We conclude that DARB is not as effective as rHuEPO in supporting
      the in vitro growth of human BFU-E.

PMID- 16604823
TI  - Decreased immunoreactive maspin expression in intermediate thickness and thick
      primary melanoma lesions.
AB  - Maspin is a member of the serpin family of protease inhibitors. It is a 42 kDa
      cytoplasmic protein that is reported to have tumour suppressor activity. The loss
      of maspin gene expression is correlated with increased invasiveness and the risk
      of metastases in breast cancer. We studied maspin expression in primary melanoma
      lesions obtained from 76 patients. Immunostaining of 5 pm sections for maspin
      expression was obtained using the citrate antigen retrieval method. The extent of
      immunostaining was scored by recording the proportion of immunoreactive cells and
      the intensity of immunostaining. Our results demonstrated that maspin expression
      was down-regulated in intermediate thickness and thick melanoma lesions compared
      with thin lesions. These results suggest that loss of maspin expression might
      play a role in melanoma progression, invasion and metastatic dissemination.
      Further studies are needed to clarify the clinicopathological significance of
      maspin expression in melanoma.

PMID- 16604824
TI  - Effects of selective brain cooling in patients with severe traumatic brain
      injury: a preliminary study.
AB  - We prospectively investigated non-invasive selective brain cooling (SBC) in
      patients with severe traumatic brain injury. Sixty-six in-patients were
      randomized into three groups. In one group, brain temperature was maintained at
      33 - 35 degrees C by cooling the head and neck (SBC); in a second group, mild
      systemic hypothermia (MSH; rectal temperature 33 - 35 degrees C) was produced
      with a cooling blanket; and a control group was not exposed to hypothermia.
      Natural rewarming began after 3 days. Mean intracranial pressure 24, 48 or 72 h
      after injury was significantly lower in the SBC group than in the control group.
      Mean serum superoxide dismutase levels on Days 3 and 7 after injury in the SBC
      and MSH groups were significantly higher than in the control group. The
      percentage of patients with a good neurological outcome 2 years after injury was
      72.7%, 57.1% and 34.8% in the SBC, MSH and control groups, respectively.
      Complications were managed without severe sequelae. Non-invasive SBC was safe and
      effective.

PMID- 16604825
TI  - The 5-hydroxytryptamine2A receptor antagonist sarpogrelate hydrochloride inhibits
      acute platelet aggregation in injured endothelium.
AB  - In this study, the effect of sarpogrelate hydrochloride, a 5-hydroxytryptamine2A
      receptor antagonist, on platelet aggregation at the site of injured carotid
      artery endothelium was examined. The rat common carotid artery was clamped for 30
      min to induce endothelial injury. Sarpogrelate hydrochloride was administered
      before and after the injury, and the effects were compared with those in rats
      receiving sham operation only and those receiving clipping injury but no
      sarpogrelate hydrochloride. The animals were killed 24 h after the procedure. The
      common carotid artery was examined by scanning electron microscopy and stained
      immunochemically for factor VIII. Sarpogrelate hydrochloride treatment was
      associated with reduced aggregation of platelets on electron microscopy and lower
      expression of factor VIII at the injured intima. Sarpogrelate hydrochloride has
      an inhibitory effect on platelet aggregation at the intima in the acute stage
      after injury, suggesting that this drug may be used to prevent early ischaemic
      complications after surgical or endovascular arterial intervention.

PMID- 16604826
TI  - Comparison of letrozole and clomiphene citrate in women with polycystic ovaries
      undergoing ovarian stimulation.
AB  - Letrozole was compared with clomiphene citrate (CC) as a first-line treatment for
      ovulation induction in women with polycystic ovaries (PCOs). A total of 106 women
      with primary infertility and a diagnosis of PCOs were randomized to receive
      either 100 mg CC (n = 55) or 2.5 mg letrozole (n = 51) daily for 5 days. Human
      chorionic gonadotrophin (hCG) at a dose of 10000 IU was administered when at
      least one follicle with a mean diameter > or = 18 mm was observed using
      transvaginal ultrasound. The number of mature follicles was significantly lower,
      but endometrial thickness and ovulation and pregnancy rates were significantly
      higher in the letrozole group than in the CC group. In conclusion, letrozole is
      associated with a higher pregnancy rate than CC in PCO patients and may have a
      role as a first-line treatment for anovulatory patients with PCOs.

PMID- 16604827
TI  - Comparison between high and low molecular weight hyaluronates in knee
      osteoarthritis patients: open-label, randomized, multicentre clinical trial.
AB  - Efficacy and safety of high and low molecular weight hyaluronates in knee
      osteoarthritis patients were compared in a randomized, open-label trial. Patients
      in the high molecular weight hyaluronate group were treated once weekly for 3
      weeks and in the low molecular weight group once weekly for 5 weeks. We evaluated
      weight-bearing pain, degree of flexion, swelling and knee tenderness; frequency
      and amount of rescue medication; patient and investigator global assessment of
      pain, and safety over 12 weeks after final injection of study medication.
      Significant improvements in pain and WOMAC-Likert scores were observed in both
      groups, but not between groups. Knee joint pain improvement was noted in both
      groups by patients and investigators during follow-up. Close correlation was
      observed between patient- and investigator-reported data. There was no
      significant difference in side-effects between the groups. In conclusion, the
      efficacy and safety of high and low molecular weight hyaluronate are similar.

PMID- 16604828
TI  - Oral lactoferrin in HIV-1 vertically infected children: an observational follow
      up of plasma viral load and immune parameters.
AB  - Lactoferrin (LF) is a mammalian iron-binding glycoprotein with antiviral effects.
      This preliminary study evaluated 6 months' LF (3 g/day, orally) treatment in 22
      human immunodeficiency virus type 1 (HIV-1) vertically infected children. Plasma
      viral load and CD4+ cell counts were assessed every 3 months; before, during and
      after LF administration. No significant changes were observed during the pre
      treatment period. By 6 months, mean (+/- SD) plasma viral load (log10) declined
      from 4.54 (+/- 0.65) to 4.28 (+/- 0.60); median percentage CD4+ cell count
      increased from 21.5% to 24.5%. Two months after treatment discontinuation, mean
      plasma viral load did not differ significantly from baseline or month 6 levels,
      but the percentage CD4+ cell count remained significantly higher than the
      baseline value. LF plus antiretroviral (ARV) therapy was more effective at
      increasing CD4+ cell count than LF alone. None of the patients showed any new HIV
      1-related symptoms at follow-up. LF might be a useful addition to ARV therapy,
      but further large-scale studies are required.

PMID- 16604829
TI  - Post-operative infection by pathogenic micro-organisms in the oral cavity of
      patients with prostatic carcinoma.
AB  - The aim of this study was to analyse the change in the oral cavity microflora of
      14 patients who had undergone a radical prostatectomy for prostatic carcinoma.
      The detection of micro-organisms in the oral cavity was compared before and after
      the surgical procedure. Post-operative infection, defined as those patients who
      had increased Candida species counts and/or pathogenic bacteria only at the post
      operative examination, was observed in 10 patients. Six patients showed increased
      Candida species counts at the post-operative examination compared with the pre
      operative examination. In five patients, pathogenic bacterial species were
      detected at the post-operative examination but not at the pre-operative
      examination. One patient had detectable pathogenic bacterial species only at the
      post-operative examination along with increased Candida species counts. Our
      findings suggest that pre-operative oral hygiene to remove bacterial and Candida
      species from patients who are scheduled for surgical procedures is important for
      satisfactory clinical outcomes.

PMID- 16604830
TI  - Durable molecular complete remission induced by low-dose imatinib plus low-dose
      interferon alpha in a patient with chronic myelogenous leukaemia.
AB  - A 50-year-old male was diagnosed with chronic myelogenous leukaemia (CML) in
      chronic phase in March 2000. He was treated initially with hydroxyurea,
      administered orally. This was changed to interferon alpha (IFN) 5 million units
      (5 MIU) subcutaneously daily in May 2000; complete cytogenetic response was
      achieved 11 months later. IFN dosage was reduced to 5 MIU, alternate days, in
      June 2001 and a cytogenetic relapse occurred 3 months later. Since April 2002, he
      has received IFN 5 MIU three times weekly in combination with imatinib 200
      mg/day. The Philadelphia chromosome disappeared from his peripheral blood cells
      in July 2002 and a complete molecular response was achieved in January 2003.
      Serial molecular studies between January 2004 and January 2005 showed no
      detectable major BCR/ABL chimeric transcript. Grade 2 neutropenia and grade 1 non
      haematological adverse effects have been observed. This case report suggests the
      combination of low-dose imatinib and IFN would be tolerable and effective for CML
      patients in chronic phase.

PMID- 16604831
TI  - A rare case of recurrent alpha-fetoprotein-producing gastric cancer without re
      elevation of serum AFP.
AB  - We report an extremely rare case of recurrent alpha-fetoprotein (AFP)-producing
      gastric cancer without re-elevation of serum AFP. The patient was a 78-year-old
      woman with AFP-producing gastric cancer, a rare type of gastric adenocarcinoma. A
      Borrmann III gastric tumour was surgically resected and AFP-producing gastric
      cancer was diagnosed based on high levels of serum AFP (705.44 ng/ml) and
      immunohistochemical examination of the tumour. The serum AFP level decreased to
      the normal range after resection without any sign of recurrence by imaging, but
      the patient developed local recurrence of the cancer and died 13 months after
      surgery. No re-elevation of serum AFP levels was observed after recurrence.
      Although serum AFP levels are believed to be useful for follow-up in the post
      operative period, the possibility that serum AFP levels do not always correlate
      with the extent of the cancer should be kept in mind.

PMID- 16604832
TI  - Painful neuropathy with trigeminal nerve involvement in type 2 diabetes.
AB  - After several years of treatment for type 2 diabetes mellitus, a 69-year-old
      Japanese man developed an acute painful neuropathy, characterized by bilateral
      causalgia and dysaesthesia in his cheeks and around his eyes, typically 30 min to
      3 h after meals. As his glycaemic control deteriorated, his haemoglobin (Hb) A1c
      level gradually increased from 7 - 8% to 10.3% and his symptoms became more
      severe. The pain radiated out along the distribution of the ophthalmic and
      maxillary divisions of the trigeminal nerve. The patient was treated with insulin
      therapy and his HbA1c level decreased from 10.3% to 6.8% within 7 months. Five
      months after initiating insulin therapy, his symptoms showed a dramatic
      improvement. This was a very unusual case of bilateral acute painful neuropathy
      that involved the ophthalmic and maxillary divisions of the trigeminal nerve, and
      in which aggravation of the symptoms clearly related to poor glycaemic control.

PMID- 16604833
TI  - Serum galectin-3 in advanced melanoma patients: a hypothesis on a possible role
      in melanoma progression and inflammation.

PMID- 16604834
TI  - A public health evaluation of recreational water impairment.
AB  - Water quality objectives for body contact recreation (REC-1) in Newport Bay, CA
      are not being attained. To evaluate the health implications of this non
      attainment, a comprehensive health-based investigation was designed and
      implemented. Bacterial indicator data indicate that exceedances of the water
      quality objectives are temporally sporadic, geographically limited and most
      commonly occur during the time of the year and/or in areas of the bay where the
      REC-1 use is low or non-existent. A disease transmission model produced simulated
      risk estimates for recreation in the Bay that were below levels considered
      tolerable by the US EPA (median estimate 0.9 illnesses per 1,000 recreation
      events). Control measures to reduce pathogen loading to Newport Bay are predicted
      to reduce risk by an additional 16% to 50%. The results of this study indicate
      that interpreting the public health implications of fecal indicator data in
      recreational water may require a more rigorous approach than is currently used.

PMID- 16604835
TI  - Bushfires and tank rainwater quality: a cause for concern?
AB  - In early 2003, after a prolonged drought period, extensive bushfires occurred in
      the east of Victoria affecting 1.5 million hectares of land. At the time, smoke
      and ash from bushfires, settling on roofs, contained pollutants that could
      potentially contaminate rainwater collected and stored in tanks for domestic use.
      The major concerns include polycyclic aromatic hydrocarbons (PAHs) from
      incomplete combustion of organic matter and arsenic from burnt copper chrome
      arsenate (CCA) treated wood. An increase in microbial contamination through
      altered nutrient levels was also hypothesised. A pilot study of 49 rainwater tank
      owners was undertaken in north-east Victoria. A rainwater tank sample was taken
      and analysed for a variety of parameters including organic compounds,
      microbiological indicators, metals, nutrients and physico-chemical parameters. A
      survey was administered concurrently. A number of results were outside the
      Australian Drinking Water Guideline (ADWG) values for metals and microbiological
      indicator organisms, but not for any tested organic compounds. PAHs and arsenic
      are unlikely to be elevated in rainwater tanks as a result of bushfires, but
      cadmium may be of concern.

PMID- 16604836
TI  - Neurosensory effects of chronic exposure to arsenic via drinking water in Inner
      Mongolia: I. Signs, symptoms and pinprick testing.
AB  - This study was designed to assess the effects of exposure to arsenic in drinking
      water on neurosensory function. A questionnaire including neurological signs and
      symptoms and a brief neurological exam consisting of pinprick testing of the arms
      and legs and knee-jerk test were administered to 321 residents of the Bamen
      region of Inner Mongolia, China. Arsenic in water was measured by hydride
      generation atomic fluorescence. Participants were divided into three exposure
      groups--low (non-detectible-20), medium (100-300) and high (400-700 microg/I)
      arsenic. Significant group differences were observed in pinprick scores for all
      four limbs. Results indicate that arsenic alters pinprick (pain) thresholds at
      well-water concentrations as low as 400 microg/l, well below the 1000 microg/l
      threshold for neurological effect specified by NRC (1999). Regression models
      suggest that a 50% increase in pinprick score is associated with a 71-159 ppb
      increase in arsenic concentration.

PMID- 16604837
TI  - Neurosensory effects of chronic exposure to arsenic via drinking water in Inner
      Mongolia: II. Vibrotactile and visual function.
AB  - This study was designed to assess the effects of exposure to arsenic in drinking
      water on visual and vibrotactile function in residents of the Bamen region of
      Inner Mongolia, China. Arsenic was measured by hydride generation atomic
      fluorescence. 321 participants were divided into three exposure groups- low (non
      detectable-20), medium (100-300) and high (400-700 microg/l) arsenic in drinking
      water (AsW). Three visual tests were administered: acuity, contrast sensitivity
      and color discrimination (Lanthony's Desaturated 15 Hue Test). Vibration
      thresholds were measured with a vibrothesiometer. Vibration thresholds were
      significantly elevated in the high exposure group compared to other groups.
      Further analysis using a spline regression model suggested that the threshold for
      vibratory effects is between 150-170 microg/l AsW. These findings provide the
      first evidence that chronic exposure to arsenic in drinking water impairs
      vibrotactile thresholds. The results also indicate that arsenic affects
      neurological function well below the 1000 microg/I concentration reported by NRC
      (1999). No evidence of arsenic-related effects on visual function was found.

PMID- 16604838
TI  - Quantitative microbial risk assessment to estimate health risks attributable to
      water supply: can the technique be applied in developing countries with limited
      data?
AB  - In the 3rd edition of its Guidelines for Drinking-Water Quality (2004) (GDWQ) the
      World Health Organization (WHO) promotes the use of risk assessment coupled with
      risk management for the control of water safety in drinking water supplies.
      Quantitative microbial risk assessment (QMRA) provides a tool for estimating the
      disease-burden from pathogenic microorganisms in water using information about
      the distribution and occurrence of the pathogen or an appropriate surrogate. This
      information may then be used to inform decisions about appropriate management of
      the water supply system. Although QMRA has been used to estimate disease burden
      from water supplies in developed countries, the method has not been evaluated in
      developing countries where relevant data may be scarce. In this paper, we
      describe a simplified risk assessment procedure to calculate the disease burden
      from three reference pathogens--pathogenic Escherichia coli, Cryptosporidium
      parvum and rotavirus--in water supplies in Kampala, Uganda. The study shows how
      QMRA can be used in countries with limited data, and that the outcome can provide
      valuable information for the management of water supplies.

PMID- 16604839
TI  - Detection of Salmonella spp. in water using magnetic capture hybridization
      combined with PCR or real-time PCR.
AB  - The removal of target DNA by magnetic capture hybridization (MCH) from
      constituents inhibitory to amplification by polymerase chain reaction (PCR) was
      evaluated using Salmonella as the test pathogen. Hybrids were subjected to both
      conventional and quantitative real-time PCR (qPCR). When PCR inhibitors commonly
      found in water were added to the reaction, MCH-PCR increased the detection
      sensitivity on the order of 8 to 2,000-fold compared with the system using only
      PCR. To determine the selectivity of MCH for target DNA (Salmonella), different
      amounts of non-target DNA (Escherichia coli) were added to the qPCR reaction. The
      highest non-target DNA concentration interfered with the amplification by qPCR
      alone, while MCH-qPCR was unaffected. Average recovery of Salmonella DNA by MCH
      qPCR was 31% using optimized buffers, washing solutions and enzymatic digestion.
      A recovery function was proposed in order to calculate the real cell number based
      on the measured value. Preliminary testing confirmed the suitability of this
      method for analysis of natural waters.

PMID- 16604840
TI  - Effects of large-scale poultry farms on aquatic microbial communities: a
      molecular investigation.
AB  - The effects of large-scale poultry production operations on water quality and
      human health are largely unknown. Poultry litter is frequently applied as
      fertilizer to agricultural lands adjacent to large poultry farms. Run-off from
      the land introduces a variety of stressors into the surface waters including
      nutrients, antimicrobials and pathogenic bacteria. The Delaware, Maryland and
      Virginia (Delmarva) Peninsula has the highest concentration of broiler chickens
      per farm acre in the United States and provides an ideal location for studying
      the effects of stressors from poultry farms. We investigated potential effects by
      characterizing shifts in the structure of aquatic bacterial communities. DNA was
      isolated from microorganisms in water samples from streams and rivers at varying
      distances from, or having different frequencies of, litter applications.
      Fingerprints of 16S rDNA amplicons from bacteria in water samples collected
      during late summer 2001 to late spring 2002 were produced by denaturing gradient
      gel electrophoresis (DGGE). A statistical analysis of multiple fingerprints from
      each sampling location demonstrated that each site harboured a bacterial
      community significantly different from the communities at other sites. Similarly,
      the bacterial communities from each sampling time differed significantly from
      communities at other sampling times. Most importantly, a competitive, library
      based analysis showed time of sampling (month) had a greater effect on community
      structure than did location.

PMID- 16604842
TI  - A study of the efficacy of various home filtration substrates in the removal of
      microcystin-LR from drinking water.
AB  - This study was conducted to determine whether common water filtration and
      purification systems bought by consumers and used in the home would remove
      cyanotoxins from water. Commonly used universal filter housings and filter sizes
      were utilized to identify filter media that may be effective in the removal of
      microcystin-LR in deionized water. Results suggest that the efficacy of home
      filtration devices in removing microcystin-LR varies considerably with the type
      of device being used. Carbon filters successfully removed microcystin-LR allowing
      only 0.05-0.3% of the toxin load to pass through the filter. On the other hand,
      pleated paper and string wound filters allowed > 90% of microcystin-LR present in
      the sample to pass through the filters. Theoretically, the use of carbon home
      filtration devices tested in this study may provide protection against human
      exposure to cyanotoxin in addition to protection provided by water treatment
      methodologies utilized in water treatment facilities. Further studies need to be
      done to assess the efficacy of home filtration devices for various cyanotoxins
      and for other filtering conditions such as increased toxin load, the presence of
      other contaminants in drinking water, and the repetitive use of the same filter
      over longer time intervals.

PMID- 16604841
TI  - Association of Cryptosporidium with bovine faecal particles and implications for
      risk reduction by settling within water supply reservoirs.
AB  - Artificial cow pats were seeded with Cryptosporidium oocysts and subjected to a
      simulated rainfall event. The runoff from the faecal pat was collected and
      different particle size fractions were collected within settling columns by
      exploiting the size-dependent settling velocities. Particle size and
      Cryptosporidium concentration distribution at 10 cm below the surface was
      measured at regular intervals over 24 h. Initially a large proportion of the
      total volume of particles belonged to the larger size classes (> 17 microm).
      However, throughout the course of the experiment, there was a sequential loss of
      the larger size classes from the sampling depth and a predominance of smaller
      particles (< 17 microm). The Cryptosporidium concentration at 10 cm depth did not
      change throughout the experiment. In the second experiment samples were taken
      from different depths within the settling column. Initially 26% of particles were
      in the size range 124-492 microm. However, as these large particles settled there
      was an enrichment at 30 cm after one hour (36.5-49.3%). There was a concomitant
      enrichment of smaller particles near the surface after 1 h and 24 h. For Pat 1
      there was no difference in Cryptosporidium concentration with depth after 1 h and
      24 h. In Pat 2 there was a difference in concentration between the surface and 30
      cm after 24 h. However, this could be explained by the settling velocity of a
      single oocyst. The results suggested that oocysts are not associated with large
      particles, but exist in faecal runoff as single oocysts and hence have a low (0.1
      m(d-1)) settling velocity. The implications of this low settling velocity on
      Cryptosporidium risk reduction within water supply reservoirs was investigated
      through the application of a three-dimensional model of oocyst fate and transport
      to a moderately sized reservoir (26 GL). The model indicated that the role of
      settling on oocyst concentration reduction within the water column is between one
      and three orders of magnitude less than that caused by advection and dilution,
      depending on the strength of hydrodynamic forcing.

PMID- 16604843
TI  - Variation of microorganism concentrations in urban stormwater runoff with land
      use and seasons.
AB  - Stormwater runoff samples were collected from outfalls draining small municipal
      separate storm sewer systems. The samples were collected from three different
      land use areas based on local designation (high-density residential, low-density
      residential and landscaped commercial). The concentrations of microorganisms in
      the stormwater runoff were found to be similar in magnitude to, but less variable
      than, those reported in the stormwater National Pollutant Discharge Elimination
      System (NPDES) database. Microorganism concentrations from high-density
      residential areas were higher than those associated with low-density residential
      and landscaped commercial areas. Since the outfalls were free of sanitary
      wastewater cross-connections, the major sources of microorganisms to the
      stormwater runoff were most likely from the feces of domestic animals and
      wildlife. Concentrations of microorganisms were significantly affected by the
      season during which the samples were collected. The lowest concentrations were
      observed during winter except for Staphylococcus aureus. The Pearson correlation
      coefficients among different indicators showed weak linear relationships and the
      relationships were statistically significant. However, the relationships between
      indicators and pathogens were poorly correlated and were not statistically
      significant, suggesting the use of indicators as evidence of the presence of
      pathogens is not appropriate. Further, the correlation between the concentration
      of the traditionally monitored indicators (total coliforms and fecal coliforms)
      and the suggested substitutes (enterococci and E. coli) is weak, but
      statistically significant, suggesting that historical time series will be only a
      qualitative indicator of impaired waters under the revised criteria for
      recreational water quality by the US EPA.

PMID- 16604844
TI  - Drinking water consumption patterns of residents in a Canadian community.
AB  - A cross-sectional survey using computer-assisted telephone interviewing was
      performed to assess the drinking water consumption patterns in a Canadian
      community, and to examine the associations between these patterns and various
      demographic characteristics. The median amount of water consumed daily was four
      250 ml servings (1.01), although responses were highly variable (0 to 8.01).
      Bottled water consumption was common, and represented the primary source of
      drinking water for approximately 27% of respondents. Approximately 49% of
      households used water treatment devices to treat their tap water. The observed
      associations between some demographic characteristics and drinking water
      consumption patterns indicated potential differences in risk of exposure to
      waterborne hazards in the population. Our results lend support to the federal
      review of the bottled water regulations currently in progress in Canada.
      Additionally, they may lend support to a provincial/territorial government review
      of bottled water regulations, and both federal and provincial/territorial level
      reviews of the water treatment device industry. Further investigation of the use
      of alternative water sources and the perceptions of drinking water in Canada is
      also needed to better understand, and subsequently address, concerns among
      Canadians.

PMID- 16604845
TI  - Optimization of regenerated bone char for fluoride removal in drinking water: a
      case study in Tanzania.
AB  - This paper presents findings of a study on optimization and application of the
      regenerated bone char media for the defluoridation of drinking water in Tanzania
      where more than 30% of all water sources have fluoride concentrations above the
      1.50 mg/I which is recommended by the World Heath Organization (WHO). In this
      study, regeneration temperature, regeneration duration, contact time, regenerated
      bone char dosage and particle size were investigated. Results indicate that the
      highest fluoride removal and adsorption capacity were 70.64% and 0.75 mg-F/g-bc,
      respectively, for a sample with bone char material that was regenerated at 500
      degrees C. In this study the optimum burning duration was found to be 120 min,
      which resulted in residual fluoride that varied from a maximum value of 17.43
      mg/I for a 2 min contact time to a minimum value of 8.53 mg/I for a contact time
      of 180 min. This study further indicated that the smallest size of regenerated
      bone char media (0.5-1.0 mm diameter) had the highest defluoridation capacity,
      with residual fluoride which varied from 17.82 mg/I at 2 min contact time to
      11.26 mg/I at 120 min contact time. In terms of dosage of the regenerated bone
      char media it was established that the optimum dosage was 25g of bone char media
      with a grain size of 0.50-1.0 mm. This had a fluoride removal capacity of 0.55 mg
      F/g-BC. Column filter experiments indicated that regenerated bone media is
      capable of removing fluoride from dinking water to meet both WHO and Tanzania
      recommended values.

PMID- 16604846
TI  - Decentralization and health care in the former Yugoslav Republic of Macedonia.
AB  - Since its independence in 1991, the Republic of Macedonia became a highly
      centralized state, with most relevant decisions taken at the central level in
      Skopje, resembling the highly centralized system, which once characterized Former
      Yugoslavia. As agreed in the Framework Agreement, which ended six months of
      internal conflict, the Macedonian Government will decentralize public services
      delivery, including social protection, health, education, and infrastructure over
      the course of the next few years. Within health care, it is argued that by
      placing policy-making authority and operating control closer to the client,
      decentralization will reduce some of the inequities in service provision and
      inefficiencies present within the current centrally controlled system. In
      principle, local voters will have more information on the price and quality of
      services, thereby increasing competition in the sector and strengthening the
      private sector. The emphasis on market incentives resulting in greater efficiency
      and better management of health care institutions is viewed as one of the
      benefits of privatization. Critics of decentralization and the subsequent
      privatization of public services fear it may result in an erosion of quality and
      consistency across regions, leaving some regions, cities, villages and
      potentially vulnerable groups worse off than others. The paper argues that if the
      institutional weaknesses in Macedonia have not been addressed, decentralisation
      could result in further excluding the rural population from health care
      provision. Similarly, the need for a clear delineation of responsibilities and
      functions among different levels and institutions is outlined.

PMID- 16604847
TI  - Regional group purchasing of vaccines: review of the Pan American Health
      Organization EPI revolving fund and the Gulf Cooperation Council group purchasing
      program.
AB  - This paper reviews the key design features, accomplishments of and lessons
      learned from two regional group procurement mechanisms dealing with vaccines that
      have been in operation for more than 25 years. The Pan American Health
      Organization (PAHO) EPI Revolving Fund purchases vaccines and immunization
      supplies on behalf of more than 35 countries in the Latin American and Caribbean
      region. Based on a 'central contracting' model, the program handles most aspects
      of procurement-from tendering to contracting with and paying producers--using a
      common fund to pay producers before being reimbursed by countries once goods are
      received in-country. The Gulf Cooperation Council (GCC) Group Purchasing Program
      among seven Persian Gulf States issues joint tenders for vaccines, as well as
      drugs and other medical goods. Through this 'group contracting' program,
      countries are responsible for contracting with and paying producers on their own,
      once the group has selected winning bids. Both programs have experienced
      substantial growth in the past two decades and are considered to have contributed
      to or accelerated achievements of immunization programs in both regions,
      including the introduction of new vaccines. The paper identifies several features
      of both programs--both those designed to attract country participation and those
      designed to ensure the programs' financial viability--which help explain their
      success and longevity.

PMID- 16604848
TI  - Will more inputs improve the delivery of health services? Analysis of district
      vaccination coverage in Pakistan.
AB  - In order to determine whether physical resources or technical inputs can make a
      difference to the delivery of health services, we carried out a study that
      examined the large variation in district level vaccination coverage in Pakistan.
      Vaccination coverage was assessed by district-wise cluster surveys and the
      predictor variables were collected from census data and from a survey of 99
      district health offices. Information was collected on basic supplies, physical
      infrastructure, management, training, socio-economic variables, and a variety of
      other indicators. Univariate and multivariate analyses were carried out. A model
      including female literacy rate, TV ownership, and provincial dummies explained
      48% of the variation in DTP3 coverage. Very few of the other variables examined
      were significantly correlated to coverage. Possible explanatory variables like
      adequacy of syringe and vaccine supply, the number of vaccinators per capita,
      recent training of managers, frequency of supervision, availability of micro
      plans, and turnover of managers were not correlated with coverage. While the
      Government of Pakistan has ensured that many physical resources and technical
      inputs have been provided to the district health offices, this does not appear
      able to explain the relatively low overall coverage or the variation between
      districts. Bolder initiatives and innovations are likely needed to improve
      delivery of basic health services.

PMID- 16604849
TI  - Developing management systems with cross-cultural fit: assessing international
      differences in operational systems.
AB  - Experiences in the Yunnan Maternal and Child Health Project, a 6-year CAN 6
      million dollars bilateral initiative implemented in 10 counties (population 2.4
      million) in Yunnan, China, are used to illustrate management approaches that
      successfully bridge cross-cultural differences in operational systems between
      donor and recipient countries. Donor institutions, local implementing agencies,
      and partner executing organizations each operate within specific assumptions
      about how governance structures, financial and administrative systems, human
      resource infrastructure, communications systems, and monitoring and reporting
      mechanisms function. These 'system domains' vary across cultures and countries,
      and become more evident as projects deal with capacity constraints, concerns
      about accountability, and rapid socioeconomic and political change during
      implementation. Management teams must be able to identify areas of poor fit among
      operational systems and respond appropriately. An assessment tool is offered,
      which management partners can use, as a basis for joint reflections on potential
      risks, identification of mitigation strategies, and establishing operational
      systems that are a fit for the funder as well as for partner agencies responsible
      for executing the project.

PMID- 16604850
TI  - Integration and collaboration in public health--a conceptual framework.
AB  - With the increasing differentiation of organisations involved in the pursuit of
      public health, there is also a growing need for inter-organisational integration.
      Starting from the concepts of differentiation and integration, this article is
      attempting a theoretical reconstruction based on published research on inter
      organisational integration in public health and related welfare services.
      Different forms of integration are defined and related to each other in a
      conceptual framework, which is in itself an integration of different theoretical
      perspectives. According to this framework, integration in the field of public
      health requires inter-organisational collaboration across different sectors of
      the society. Such intersectoral collaboration can be organised mainly in the form
      of multidisciplinary teams across the boundaries of different organisations and
      sectors. Such an organisation is fragile and volatile, however, which means that
      it needs a lot of management support in order to survive.

PMID- 16604851
TI  - Calling the plays.

PMID- 16604852
TI  - A few more points on chronobiology.

PMID- 16604853
TI  - Doctoring the old-fashioned way.

PMID- 16604854
TI  - Getting quick to serve the sick.

PMID- 16604855
TI  - Faith and practice.

PMID- 16604857
TI  - Warning bumps can direct us to better care.

PMID- 16604856
TI  - Big push.

PMID- 16604858
TI  - Juice, the new cookie.

PMID- 16604860
TI  - Minimalist.

PMID- 16604859
TI  - When the pain won't go away.

PMID- 16604861
TI  - Retooling family medicine.

PMID- 16604862
TI  - A pandemic of fear.

PMID- 16604863
TI  - Avian flu is coming!

PMID- 16604864
TI  - The crisis in primary care.

PMID- 16604865
TI  - Enhancing the role of internal medicine subspecialty societies in defining
      quality of care.

PMID- 16604866
TI  - Factors influencing patients' choice of primary medical doctors.
AB  - This study investigated factors that influence adult patients' choice of primary
      care physicians and aimed to determine whether patients know the difference
      between internal medicine and family medicine. One thousand patients who had seen
      their primary care physician in either the family medicine or internal medicine
      department at Mayo Clinic in 2001 were sent a questionnaire to determine 1) the
      factors that influenced their choice of physician and 2) their knowledge of the
      characteristics of both specialties. Forty-six percent of the patients responded.
      Patients most often cited the doctor's "Approach to patient care" and
      "Interpersonal skills/communication" as affecting their choice of physician.
      Results also showed patient knowledge of the difference between family medicine
      and internal medicine was poor. The authors conclude that patients must be
      educated about the differences in the training of and care provided by different
      types of primary care physicians.

PMID- 16604867
TI  - The Minnesota Medical Home Learning Collaborative: a step to improving care for
      Minnesota's children with special health care needs.
AB  - Minnesota's Medical Home Learning Collaborative is now starting its third year of
      operation. This article discusses the concept of medical home, the rationale for
      its use, and the progress and challenges encountered so far in the 11 clinics
      that have participated in the collaborative since it began and the five that
      joined this past September.

PMID- 16604868
TI  - House calls.

PMID- 16604869
TI  - [Rheumatic diseases and infections].

PMID- 16604870
TI  - [Septic arthritis].
AB  - Septic arthritis is a medical emergency that may be associated with significant
      mortality (10-15%) and morbidity (25-50%), in case of delayed management. When
      septic arthritis is suspected, arthrocentesis and culture of the synovial fluid
      are the gold standard. The absence of fever, rigors, leukocytosis or elevated
      erythrocyte sedimentation rate does not exclude the diagnosis of septic
      arthritis. Age, chronic arthropathy, or arthroplasty are particularly associated
      with increased morbidity. Therapy consists in antibiotics, joint immobilisation
      (maximum 3 days) and medical drainage, in case of persisting joint effusion.

PMID- 16604871
TI  - [Infectious spondylodiscitis: the surgical approach].
AB  - Introduction of antibiotics in the last century and recent progress in surgical
      techniques have significantly reduced mortality and morbidity rates of
      spondylodiscitis. However, when unrecognized, it can have catastrophic
      consequences for the patient. Antibiotic drugs remain the cornerstone of
      treatment, and surgery is to be discussed in general as a last resource in case
      of acute neurologic deficit or severe sagittal or frontal spinal imbalance.
      Metallic implants are not absolutely contraindicated in surgical treatment of
      spondylodiscitis and relapse of infection has been reported to be rare. In case
      of severe mechanical instability and neurologic deficit, they even are
      indispensable and complications can be avoided by accurately identifying the germ
      and by treating infection with the adequate antibiotic beforehand.

PMID- 16604872
TI  - [Infectious spondylodiscitis: the rheumatologist's point of view].
AB  - Infectious spondylodiscitis is increasingly prevalent in the elderly population.
      Despite modern imagery techniques, time between onset of symptoms and diagnosis
      is still important and directly affects mortality rate. The systematic use of red
      flags for back pain patients should be able to improve this situation. In case of
      clinical and radiological suspicion of infectious spondylodiscitis, every effort
      should be directed toward the characterization of the bacteria before the
      introduction of antibiotics. Most of the time conservative treatment with
      antibiotics and bracing is appropriate but in selected cases a surgical procedure
      is advised, specifically in case of severe motor deficit or in the presence of
      non-tuberculosis abscess.

PMID- 16604873
TI  - [Reactive arthritis].
AB  - Reactive arthritis is a disease closely related to the presence of the HLA-B27
      antigen and characterized by sterile joint inflammation secondary to infection.
      Arthritis is only one of the clinical manifestations of this systemic disease.
      Its diagnosis rests on history, clinical examination and various serologies. The
      prognosis is generally good, but recurrences are frequent, in particular in HLA
      B27 positive patients. Treatment is mainly symptomatic, and antibiotics should be
      prescribed only in the event of an active infection. A 3 months course of
      antibiotics could be beneficial on the long-term evolution in HLA-B27 positive
      patients, but this practice deserves to be confirmed by additional randomized
      controlled studies.

PMID- 16604874
TI  - [Lyme borreliosis: from the erythema migrans to Lyme arthritis].
AB  - An outbreak of arthritis (Lyme arthritis) initiated the research leading to the
      description of the Lyme disease in the years 1977-78 as a multisystemic tick
      borne disease. Five years later the spirochete responsible for Lyme disease is
      discovered and will be named Borrelia burgdorferi, in honor to its discoverer, Dr
      Willy Burgdorfer. Presently in Europe, 6 Borrelia species have been described and
      current knowledge on epidemiology is reported here. Practical advises for the
      diagnostic of Lyme arthritis are proposed.

PMID- 16604875
TI  - [Viral arthritis].
AB  - Viral arthritis are very frequent and usually self limited to a few weeks. The
      most common pathophysiological mechanism is immune complexes deposit and not a
      direct invasion of the synovium. The typical clinical presentation is a
      peripheral and symmetrical polyarthritis, undistinguishable from other
      inflammatory arthritis. If virtually any virus can cause arthritis, it seems
      reasonable to limit investigations to the demonstration of the few viruses for
      which the therapy would be modified, namely hepatitis viruses and HIV. Serology
      remains the most common method to establish the diagnosis. From a therapeutic
      point of view, there is no specific treatment. Simple symptomatic measurements
      are sufficient.

PMID- 16604876
TI  - [Infectious risks of immunomodulating therapies in rheumatology].
AB  - Corticosteroids and cytotoxic drugs form the conventional immunomodulators in
      rheumatology. This therapeutic arsenal has recently been widened by TNF-alpha
      antagonists and other anti-cytokines. If rheumatoid arthritis is itself
      associated with infections, immunomodulating therapies further increase the risk
      of infection, especially when used in combination therapies. Among conventional
      therapies, corticosteroids are associated with the highest risk for both common
      bacterial and opportunistic infections. Infliximab is the TNF-alpha antagonist
      associated with the highest risk of infection. Its use has been particularly
      associated with cases of severe tuberculosis. All patients at risk for
      tuberculosis, treated with corticosteroids or TNF-alpha antagonists, should
      therefore receive an adequate prophylaxis.

PMID- 16604878
TI  - [Acupuncture and medications of equal efficacy for migraine].

PMID- 16604877
TI  - [Abdominal pain, indigestion and eosinophilia].
AB  - A 56 years old swiss man suffers of recurrent abdominal cramps with episodes of
      diarrhea and profuse expectorations. The routine laboratory shows principally a
      massive eosinophilia and elevated IgE in peripheral blood. After excluding the
      most frequent causes of eosinophilia, further laboratory investigations shows
      increased levels antinuclear and anti-SSA antibodies, elevated IgG4, increased
      pancreatic amylase and intestinal eosinophilia. We consider two etiologies: the
      hypereosinophilic syndrome, diagnostic of exclusion, and the autoimmune
      pancreatitis. Although we have not sufficient arguments in favour of an
      autoimmune pancreatitis, these two entities present some similar points.

PMID- 16604879
TI  - [When genetics play with fate: a conference with Boris Cyrulnik].

PMID- 16604880
TI  - [The Island of Rugen: dogs are on a leash and cats are indoors].

PMID- 16604882
TI  - [Breaking bad news].

PMID- 16604881
TI  - [Michel Servet (1511-1553), a Spanish physician in Geneva].

PMID- 16604883
TI  - Traumatic brain injury and the goals of care.

PMID- 16604884
TI  - Do researchers learn to practice misbehavior?

PMID- 16604885
TI  - The debate over liberal eugenics.

PMID- 16604886
TI  - The debate over liberal eugenics.

PMID- 16604887
TI  - The debate over liberal eugenics.

PMID- 16604888
TI  - Not DEA'd yet: Gonzales v. Oregon.

PMID- 16604889
TI  - The elephant in the room.

PMID- 16604890
TI  - Federal executive power and communicable disease control: CDC quarantine
      regulations.

PMID- 16604891
TI  - No method, thus madness?

PMID- 16604892
TI  - Competent refusal of nursing care.

PMID- 16604893
TI  - Magic eggs and the frontier of stem cell science.

PMID- 16604894
TI  - Sex, politics, and morality at the FDA: reflections on the Plan B decision.

PMID- 16604895
TI  - The rights of "Unborn children" and the value of pregnant women.

PMID- 16604896
TI  - Traumatic brain injury and the goals of care. The ordeal of reminding.

PMID- 16604897
TI  - What does vulnerability mean?

PMID- 16604899
TI  - Would my story get me a kidney?

PMID- 16604900
TI  - Evidence-based management reconsidered.
AB  - Reports of medical mistakes have splashed across newspapers and magazines in the
      United States. At the same time, instances of overuse, underuse, and misuse of
      management tactics and strategies receive far less attention. The sense of
      urgency associated with improving the quality of medical care does not exist with
      respect to improving the quality of management decision making. A more evidence
      based approach would improve the competence of the decision-makers and their
      motivation to use more scientific methods when making a decision. The authors of
      this article consider a study of 68 U.S. health services managers that found a
      low level of evidence-based management behaviors. From the findings, four
      strategies are suggested to increase health systems managers' use of research
      evidence to improve decision making: focusing evidence-based decision making on
      strategically important issues, developing committees and other structures to
      diffuse management research throughout the organization, building a management
      culture that values research, and training managers in the competencies required
      to apply research evidence to health services management decisions. To aid the
      manager in understanding and applying an evidenced-based approach to decision
      making, the article provides practical tools, techniques, and resources for
      immediate use.

PMID- 16604901
TI  - Promoting evidence-based management.

PMID- 16604902
TI  - Toward the evolution of a newly skilled managerial class for healthcare
      organizations.

PMID- 16604905
TI  - [Children want to feel comfortable in their skin].

PMID- 16604903
TI  - Making evidence-based management usable in practice.
AB  - I applaud doctors Kovner and Rundall for attempting to address the critical
      management principle of evidence-based management, but encourage them to further
      study why this principle has not been used more extensively in healthcare
      organizations. The lack of application calls for new and creative approaches to
      developing evidence-based management research and for increasing the availability
      to healthcare managers. The process to access the research must not be
      excessively time-consuming or difficult if it is going to be integrated into the
      day-to-day culture of organizations. Healthcare needs to focus on how to
      integrate evidence-based management into the culture of healthcare organizations.

PMID- 16604906
TI  - [The typical patient is an eight-to-ten year-old. Interview by Margrit Bachl].

PMID- 16604907
TI  - [When laughter becomes therapeutic].

PMID- 16604908
TI  - [More transparency through individual nursing plans].

PMID- 16604909
TI  - [Launching private trade high schools].

PMID- 16604910
TI  - [Needs and harm done by intense care situations].

PMID- 16604911
TI  - [On the question of agreement].

PMID- 16604912
TI  - [Nurses write their work plans on their own].

PMID- 16604914
TI  - [Albanian nurses on the arrival of autonomy].

PMID- 16604913
TI  - [The school where one can live well].

PMID- 16604915
TI  - [Paradox on the visibility and quality of nursing].

PMID- 16604917
TI  - [A necessary clarification].

PMID- 16604916
TI  - [A precious aid in delicate situations].

PMID- 16604918
TI  - ["I am passionate about work and a prepared life"].

PMID- 16604919
TI  - [My own "Paul and Clemence"].

PMID- 16604920
TI  - [Pay attention to schools].

PMID- 16604921
TI  - ["The patient himself is the key].

PMID- 16604923
TI  - Introducing an ROI model for pharmacy services.

PMID- 16604922
TI  - States feel less inclined to issue coverage mandates.

PMID- 16604924
TI  - When should bad behavior become a covered disease?

PMID- 16604925
TI  - Higher salaries go to clinical executives who hold business degrees (except MPH).

PMID- 16604926
TI  - Deciding factor.

PMID- 16604927
TI  - New tools to detect fraud rely on discovering patterns.

PMID- 16604928
TI  - It's time for CMS to release physician Medicare claim information.

PMID- 16604929
TI  - Leveling the field for docs and plans. Interview by Patrick Mullen.

PMID- 16604930
TI  - Tiers reach new heights under Part D.

PMID- 16604931
TI  - Four or more tiers common among PDPs and MA-PD plans.

PMID- 16604932
TI  - Sharp strategy needed with new treatment options for PAH.

PMID- 16604933
TI  - Major companies behind push for quality measures.

PMID- 16604934
TI  - Health care spending to grow at current rate through 2015.

PMID- 16604935
TI  - From hierarchies to networks of professionals.

PMID- 16604936
TI  - A conversation with President Alfonso Perna.

PMID- 16604937
TI  - After endo, what supports the crown?
AB  - There are two causes of common failures in posts and implants: retention and
      stress distribution. Implants that were smooth metal cylinders have today become
      threaded metal cylinders. By using one additional hand-operated instrument, the
      thread cutter and an additional five minutes of time, a rigid, threaded, metal
      post can be placed in the root canal to support the remaining coronal dentine.
      The tooth can frequently be rebuilt as a single unit or a bridge abutment to last
      for as long as the bone supports the root. To thread or not to thread, was that
      the question?

PMID- 16604938
TI  - Glandular odontogenic cyst. Report of two cases and review of the literature.
AB  - In 1992, the World Heath Organization recognized a new type of cyst called
      glandular odontogenic cyst (GOC). Clinically, GOC usually presents as a painless,
      slow-growing swelling. The radiographic appearance is that of a large,
      multiloculated, well-defined radiolucency. GOC tends to affect the anterior
      mandible. The dental profession must be aware of the clinical significance of
      this lesion. The aggressive nature of the lesion has been reported and at least
      25% to 55% recur following curettage. If not treated on time, extensive surgery
      and alteration of function may result. Two new cases are reported.

PMID- 16604939
TI  - A new appliance for forced eruption.
AB  - The purpose of these case reports is to introduce an innovative orthodontic
      appliance to effect forced eruption. This device is useful when attempting to
      erupt teeth in the esthetic zone with minimal effect on adjacent teeth. It is
      especially indicated for adjacent teeth with esthetic restorations. The appliance
      is easy to fabricate, cost-effective and very useful in forced eruption efforts
      for the "non-restorable" tooth.

PMID- 16604940
TI  - Predictable root recession coverage.
AB  - Gingival recession, exposure of the tooth's root, is undesirable and, in many
      situations, contrary to normal physiology. Today's root coverage is predictable.
      With the use of an acellular dermal matrix membrane (Fasciablast), we can achieve
      a new blood supply and predictable coverage, with no second surgical procedure.
      Youth, esthetics and physiology are restored.

PMID- 16604941
TI  - Simplifying endodontics with EndoSequence rotary instrumentation.
AB  - Endodontics has begun to take advantage of the scientific improvements touching
      other aspects of dental care. Precision instrumentation allows the practitioner
      to develop better instrumented canals, making obturation easier and more
      predictable. Treatment predictability from precision-based instrumentation has
      allowed a leap forward in how we provide endodontic therapy.

PMID- 16604942
TI  - The Medical Reserve Corps. an opportunity for dentists to serve.
AB  - The response to the events of Sept. 11, 2001, relied on local resources and
      personnel. Aware of how important their contribution could be, many people are
      now inspired to volunteer during times of crisis. The Medical Reserve Corps is a
      community-based volunteer network of health professionals that trains to respond
      to large-scale emergencies.

PMID- 16604943
TI  - The CARE study and cardiovascular calcification.
AB  - Cardiovascular disease (CVD) remains the major mortality risk in dialysis
      patients, accounting for almost 50 percent of deaths. Risk is related to the
      increased prevalence of traditional risk factors for CVD and to the contribution
      of abnormalities in mineral metabolism as well as cardiovascular calcification.
      Hyperphosphatemia invariably is present among patients with end-stage renal
      disease and is becoming an increasingly important clinical entity. In addition to
      its role in the pathogenesis of secondary hyperparathyroidism, elevated serum
      phosphorus increases the mortality risk among these patients. The
      pathophysiologic mechanisms by which persistent hyperphosphatemia enhances
      mortality risk in dialysis patients are not yet completely understood. Given that
      inadequate control of serum phosphorus contributes to elevated calcium-phosphorus
      (Ca x P) product, hyperphosphatemia may play a key role in cardiovascular
      calcification. The National Kidney Foundation's Kidney Disease Outcomes Quality
      Initiative (K/DOQI) "Clinical Practice Guidelines for Bone Metabolism and Disease
      in Chronic Kidney Disease" recommends more stringent levels for controlling serum
      phosphorus and Ca x P product to improve patients' quality of life and longevity.
      Several studies, including the CARE study, have shown that calcium acetate is
      more cost-effective than sevelamer as a phosphate binder. Although concern has
      been raised about its purported link to cardiovascular calcification, the author
      demonstrates in this review that calcium acetate can be used effectively with
      doses of elemental calcium that meet the K/DOQI guidelines.

PMID- 16604944
TI  - Controversies in the management of hyperphosphatemia in patients with end-stage
      renal disease.

PMID- 16604946
TI  - [Toxocara canis -- the hazard in the sandbox?].

PMID- 16604945
TI  - [The regenerating heart -- hope for children with congenital heart defects].

PMID- 16604947
TI  - [Nursing of a child with heart disease and intra-aortic balloon pump].

PMID- 16604948
TI  - [Composition and care of baby skin].

PMID- 16604949
TI  - [Support of the parents of very premature newborn infants].

PMID- 16604951
TI  - [Competition and survival strategies of birth clinics].

PMID- 16604950
TI  - [Pregnancy and tumor diseases--new perspectives of the modern reproduction
      medicine].

PMID- 16604952
TI  - [Happy Birthday betaCare].

PMID- 16604953
TI  - [Researchers' team demonstrates existence of the "sixth sense"].

PMID- 16604954
TI  - [Sweetening agent aspartame as carcinogen?].

PMID- 16604955
TI  - Interventional radiology of the portal venous circulation.

PMID- 16604956
TI  - Volumetric computed tomography.

PMID- 16604957
TI  - Magnetic resonance imaging in the assessment of cystic pancreatic lesions:
      differentiation of benign and malignant lesion status.
AB  - PURPOSE: To characterize cystic pancreatic lesions and tumors with magnetic
      resonance imaging (MRI), and to assess the value of morphological criteria in
      differentiating pseudocysts versus cystic tumors and benign versus malignant
      cystic tumors. MATERIAL AND METHODS: Twenty-three patients with cystic pancreatic
      tumors or lesions underwent plain and contrast-material-enhanced MRI, including
      magnetic resonance cholangiopancreatography (MRCP). The MR findings were
      characterized and analyzed by two readers, and the role of various imaging
      criteria and combinations thereof for final lesion assignment were assessed.
      Final diagnoses were obtained from the results of open surgery (n = 19) and/or
      biopsy (n = 4). RESULTS: Final diagnoses included cystic tumors (n = 11) and
      pseudocysts (n = 12). The lesions were located in the head (56%) and body or tail
      (44%). Lesion diameters ranged from 7 to 50 mm. Various lesion contrast
      enhancement patterns were observed for both benign and malignant lesions. Serous
      cystadenomas were located in the head, they were lobulated, and had wall
      diameters < or = 2 mm; with the combination of these characteristics all patients
      with serous cystadenoma could be identified, whereas in no other patient was this
      constellation observed. CONCLUSION: MRI facilitated the diagnosis of serous
      cystadenomas, although no definite morphologic criterion for the differentiation
      between pseudocysts and mucinous cystadenomas was identified. In consideration of
      the substantial therapeutic consequences, either diagnostics in unclear cystic
      pancreatic lesions should comprise cyst fluid analysis if necessary, or eligible
      patients should be referred for surgical resection.

PMID- 16604958
TI  - Portal vein stenosis and occlusion stenting after liver transplantation in two
      adults.
AB  - We report two cases of percutaneous transhepatic stenting of the portal vein to
      treat stenosis and occlusion disclosed 5 and 18 months, respectively, after
      orthotopic liver transplantation in two adult patients. If long-term patency is
      satisfactory, this technique should allow long-term management of portal vein
      stenosis and occlusion without the use of thrombolysis.

PMID- 16604959
TI  - Computed tomography imaging of vena cava filter complications: a pictorial
      review.
AB  - Caval filters are widely used in the prevention of pulmonary embolism. Filters
      have proved to be effective, but the complication rate is not negligible.
      Computed tomography (CT) provides a complete evaluation of the filter, including
      both caval and extracaval complications. In this review, we describe the normal
      CT aspect of cava filters, the classification of complications and their CT
      findings. Technical considerations for adequate CT imaging are also highlighted.

PMID- 16604960
TI  - Interventional procedures involving portal vein circulation: a review.
AB  - Rapid development of diagnostic radiological methods during recent decades has
      been followed by development of new interventional procedures involving portal
      circulation. The majority of these interventions were developed for treatment of
      patients with symptoms secondary to portal hypertension (PH). Interventions
      involving portal vein circulation have an established position in the treatment
      of PH and other diseases, and further development of these methods can be
      expected.

PMID- 16604961
TI  - Brachytherapy technique for abdominal wall metastases of colorectal cancer:
      ultrasound-guided insertion of applicator needle and a skin preservation method.
AB  - PURPOSE: To report a technique of interstitial brachytherapy for the treatment of
      subcutaneous metastatic abdominal wall tumors. MATERIAL AND METHODS: We developed
      a brachytherapy technique consisting of ultrasound-guided insertion of applicator
      needles to avoid the organs at risk, such as intestines, and saline injection
      into the subcutaneous tissue between the tumor and the skin to decrease the skin
      dose. We encountered three patients with painful metastases from rectal carcinoma
      in the abdominal wall refractory to external radiotherapy. They were subjected to
      this brachytherapy with a single dose of 20 Gy. RESULTS: The procedure was safely
      achieved in all three patients. Long-lasting pain reduction and tumor shrinkage
      was obtained without early or late complications. CONCLUSION: This interstitial
      brachytherapy technique seems to be feasible in the treatment of metastatic
      abdominal wall tumors.

PMID- 16604962
TI  - Liver abscess associated with hepatic artery pseudoaneurysm with arteriovenous
      fistula: imaging and interventional management.
AB  - Hepatic artery pseudoaneurysm is an infrequently encountered entity that is
      usually seen secondary to trauma or surgical procedures. The clinical
      presentation is often due to complications such as massive intrahepatic or
      intraperitoneal bleeding as a result of rupture of the pseudoaneurysm into the
      biliary tree or peritoneal cavity, respectively. Hepatic artery pseudoaneurysm,
      associated with a liver abscess, has very rarely been described in the
      literature. We present the imaging features of a case of liver abscess associated
      with a hepatic artery pseudoaneurysm and complicated by rupture and formation of
      an arteriovenous fistula. The case was successfully managed by percutaneous
      endovascular embolization. The association between a hepatic artery
      pseudoaneurysm and a liver abscess must not be overlooked, bearing in mind the
      potentially fatal associated complications which can be averted or treated by
      timely intervention.

PMID- 16604963
TI  - Primary cardiac Burkett's type lymphoma: transthoracic echocardiography,
      multidetector computed tomography and magnetic resonance findings.
AB  - Although primary cardiac lymphoma is an extremely rare disease and is associated
      with high mortality, it is treatable when diagnosed appropriately. We describe
      the transthoracic echocardiography, 16-row multidetector computed tomography (16
      MDCT) and magnetic resonance findings of primary cardiac lymphoma in an
      immunocompromised patient and review of the literature.

PMID- 16604964
TI  - Standardized volume rendering for magnetic resonance angiography measurements in
      the abdominal aorta.
AB  - PURPOSE: To compare three methods for standardizing volume rendering technique
      (VRT) protocols by studying aortic diameter measurements in magnetic resonance
      angiography (MRA) datasets. MATERIAL AND METHODS: Datasets from 20 patients
      previously examined with gadolinium-enhanced MRA and with digital subtraction
      angiography (DSA) for abdominal aortic aneurysm were retrospectively evaluated by
      three independent readers. The MRA datasets were viewed using VRT with three
      different standardized transfer functions: the percentile method (Pc-VRT), the
      maximum-likelihood method (ML-VRT), and the partial range histogram method (PRH
      VRT). The aortic diameters obtained with these three methods were compared with
      freely chosen VRT parameters (F-VRT) and with maximum intensity projection (MIP)
      concerning inter-reader variability and agreement with the reference method DSA.
      RESULTS: F-VRT parameters and PRH-VRT gave significantly higher diameter values
      than DSA, whereas Pc-VRT gave significantly lower values than DSA. The highest
      interobserver variability was found for F-VRT parameters and MIP, and the lowest
      for Pc-VRT and PRH-VRT. All standardized VRT methods were significantly superior
      to both MIP and F-VRT in this respect. The agreement with DSA was best for PRH
      VRT, which was the only method with a mean error below 1 mm and which also had
      the narrowest limits of agreement (95% of cases between 2.1 mm below and 3.1 mm
      above DSA). CONCLUSION: All the standardized VRT methods compare favorably with
      MIP and VRT with freely selected parameters as regards interobserver variability.
      The partial range histogram method, although systematically overestimating vessel
      diameters, gives results closest to those of DSA.

PMID- 16604965
TI  - Assessment of organ radiation dose associated with uterine artery embolization.
AB  - PURPOSE: To evaluate the radiation dose to the skin, uterus, and ovaries during
      uterine artery embolization. MATERIAL AND METHODS: Guided uterine artery
      embolization for leiomyomata and two types of X-ray equipment with different dose
      levels were utilized during fluoroscopy in 20 women (ages ranging from 32 to 52
      years, body weights from 55 to 68 kg). The first 13 women were treated using a
      non-pulsed system A, with 3.3 mm Al filtering and, for simplicity, a fixed peak
      voltage 80 kV. During treatment of the other 7 women, a pulsed system B with 5.4
      mm Al filtering and an identical fixed voltage was used. The dose area product
      (DAP) was recorded. The vaginal dose of the first 13 patients and the peak skin
      dose of all patients were measured with thermoluminescent dosimeters (TLDs). TLDs
      were placed in the posterior vaginal fornix and on the skin at the beam entrance
      site. The uterine and ovarian doses were estimated based on the measured skin
      doses, normalized depth dose, and organ depth values. The effective dose (Deff)
      was estimated based on the observed DAP values. The measured vaginal doses and
      the corresponding estimated uterine doses were compared statistically, as were
      the DAP values from systems A and B. RESULTS: For system A, the mean fluoroscopic
      time was 20.9 min (range 12.7-31.1), and for system B 35.9 min (range 16.4-55.4).
      The mean numbers of angiographic exposures for systems A and B were 82 (range 30
      164) and 37 (range 20-72), respectively. The mean peak skin dose for system A was
      601.5 mGy (range 279-1030) and for system B 453 mGy (range 257-875). The mean DAP
      for system A was 88.6 Gycm2 (range 41.4-161.0) and for system B 52.5 Gy-cm2
      (range 20.1-107.9). Statistical analysis showed a significant difference between
      the DAP values, the DAP for system B being the lower one. The mean estimated
      effective doses from systems A and B were 32 mSv (range 15.1-58.4) and 22 mSv
      (range 9-46), respectively. The mean estimated maximum uterine and ovarian doses
      using system A were 81 mGy (range 30-247) and 85 mGy (range 24-207-),
      respectively; when using system B, the respective doses were 101 mGy (range 45
      12) and 105 mGy (range 31-246). The measured vaginal doses had a mean value of
      52.5 mGy (range 12-124). Statistical analysis revealed a significant difference
      between the estimated uterine doses and the measured vaginal doses. CONCLUSION: A
      significant difference was found between the estimated uterine doses and the
      corresponding measured vaginal doses. This has to be kept in mind when using
      vaginal doses as a substitute for the uterine dose. There was also a significant
      difference between the DAP values from systems A and B. System B, with pulsed
      fluoroscopy and greater filtration, gave the lower exposure. The maximum skin
      dose indicates that skin injuries are unlikely to occur. The ovarian doses are
      also below the threshold for temporary or permanent sterility. The stochastic
      risk for radiation-induced cancer and genetic injury to the patient's future
      children is not considered as substantial.

PMID- 16604966
TI  - Volumetric coronary angiography using the 256-detector row computed tomography
      scanner: comparison in vivo and in vitro with porcine models.
AB  - PURPOSE: To investigate the feasibility of volumetric cine imaging in human
      cardiac studies by comparing in vivo and in vitro coronary angiography using a
      256-detector row computed tomography (CT) without ECG gating. MATERIAL AND
      METHODS: The left and right coronary arteries of two domestic pigs were scanned
      in vivo and in vitro in cine mode using the 256-detector row CT. The device
      scanned approximately 100 mm in the cranio-caudal direction with one rotation,
      with a slice thickness of 0.5 mm. RESULTS: The coronary arteries could be
      observed to the third-degree branches in vitro, but could be visualized clearly
      only to the proximal portion (first-degree or second-degree branches) in vivo.
      CONCLUSION: Application of cardiac volumetric cine imaging with 256-detector row
      CT may be a promising means of obtaining diagnostic information and has potential
      for adoption to human studies.

PMID- 16604967
TI  - Effect of saline pushing after contrast material injection in abdominal
      multidetector computed tomography with the use of different iodine
      concentrations.
AB  - PURPOSE: To investigate whether saline pushing after contrast material improves
      hepatic vascular and parenchymal enhancement, and to determine whether this
      technique permits decreased contrast material concentration. MATERIAL AND
      METHODS: 120 patients who underwent hepatic multidetector computed tomography
      were divided randomly into four groups (Groups A-D): receiving 100 ml of contrast
      material (300 mgI/ml) only (A) or with 50 ml of saline solution (B); or 100 ml of
      contrast material (350 mgI/ml) only (C) or with 50 ml of saline solution (D).
      Computed tomography (CT) values of the aorta in the arterial phase, the portal
      vein in the portal venous inflow phase, and the liver in the hepatic phase were
      measured. Visualization of the hepatic artery and the portal vein by 3D CT
      angiography was evaluated as well. RESULTS: Although the enhancement values of
      the aorta were not improved significantly with saline pushing, they continued at
      a high level to the latter slices with saline pushing. The enhancement value of
      the portal vein increased significantly and CT portography was improved with
      saline pushing. The enhancement value of the liver was not improved significantly
      using saline pushing. In a comparison between groups B and C, the enhancement
      values of the aorta and portal vein and the visualization of CT arteriography and
      portography were not statistically different. CONCLUSION: The saline pushing
      technique can contribute to a decrease in contrast material concentration for 3D
      CT arteriography and portography.

PMID- 16604968
TI  - Apparent diffusion coefficient maps of pediatric mass lesions with free-breathing
      diffusion-weighted magnetic resonance: feasibility study.
AB  - PURPOSE: To assess the technical feasibility of apparent diffusion coefficient
      (ADC) mapping based on free-breathing diffusion-weighted magnetic resonance (DW
      MR) outside the CNS in children. MATERIAL AND METHODS: Twelve children with mass
      lesions of varied histopathology were scanned with short-tau inversion recovery
      (STIR), contrast-enhanced T1-weighted (CE-T1W), and diffusion-weighted (b=0, 500
      and 1000 s/mm2) sequences. ADC maps were calculated. Lesion-to-background signal
      intensity ratios were measured and compared between STIR/CE-T1W/ADC overall
      (Friedman test) and between viable embryonal tumors and other lesions (Kruskal
      Wallis test). RESULTS: ADC maps clearly depicted all lesions. Lesion-to
      background signal intensity ratios of STIR (median 3.7), CE-T1W (median 1.4), and
      ADC (median 1.6) showed no overall difference (chi-square=3.846; P=0.146), and
      there was no difference between viable embryonal tumors and other lesions within
      STIR/CE-T1W/ADC (chi-square 1.118/0.669/<0.001; P=0.290/0.414/1.000,
      respectively). CONCLUSION: ADC mapping is feasible in free-breathing imaging of
      pediatric mass lesions outside the CNS using standard clinical equipment.

PMID- 16604969
TI  - Magnetic resonance imaging findings of basal cell adenoma in Curschmann-Steinert
      myotonic dystrophy.
AB  - Myotonic dystrophy Curschmann Steinert is a common hereditary disorder that in
      some cases can be combined with cutaneous tumors, which is an association that is
      rarely described in the literature. We present the magnetic resonance imaging in
      the unusual combination of a patient with known myotonic dystrophy and recurrent
      basal cell tumor.

PMID- 16604970
TI  - Diffusion magnetic resonance imaging may provide prognostic information in
      osmotic demyelination syndrome: report of a case.
AB  - Hyponatremia and its rapid correction may cause osmotic demyelination syndrome
      (ODS) with damage to the pontine and extrapontine areas of the brain. The damage
      may become persistent or may regress and disappear during follow-up. We describe
      the case of a 35-year-old woman with chronic renal failure who was admitted to
      the emergency department with profound hyponatremia which was corrected rapidly
      after hemodialysis treatment. During follow-up, she developed quadriparesis and
      dysartria. Magnetic resonance imaging (MRI) demonstrated abnormalities
      characteristic of ODS in the pons as well as the basal ganglia with increased
      signal intensity on T2 and diffusion-weighted (DW) MRI and low apparent diffusion
      coefficient (ADC) values. After the sixth day, her clinical status improved
      progressively. Control MRI revealed rapid normalization of the ADC values during
      the first week and month parallel to the clinical improvement. However, the
      hyperintensities on T2-weighted images persisted. Four months later the MRI
      findings were completely normal. The close relationship between the ADC
      abnormality and the clinical status suggests that DW-MRI may be useful in
      predicting the prognosis of ODS.

PMID- 16604971
TI  - Magnetic resonance renography findings and their clinical associations in
      nephropathia epidemica.
AB  - PURPOSE: To evaluate, with magnetic resonance renography (MRR), the dynamics of
      renal function in patients with nephropathia epidemica (NE) and to correlate the
      findings with the clinical course of NE. MATERIAL AND METHODS: MRR was performed
      on 20 hospitalized NE patients during the acute phase of the disease. A repeat
      MRR study was done 5-8 months later. Primary and repeat MRR studies were compared
      and functional findings evaluated. RESULTS: The uptake slope of the contrast
      enhancement curve was abnormal in the primary study in 14 patients, maximum level
      of enhancement in 11, decreasing slope of contrast enhancement curve in 14, and
      signal drop at time in 10 patients when the primary and repeat studies were
      compared. The greater change in the uptake slope of contrast enhancement, maximum
      level of enhancement, decreasing slope of enhancement, and signal drop at time
      between primary and repeat MRR studies evinced a mild association with the
      severity of clinical renal insufficiency and fluid volume overload. CONCLUSION:
      Measurable functional MRR findings were recorded in 14/20 NE patients. The
      severity of the findings was mildly associated with the degree of clinical renal
      insufficiency and fluid volume overload.

PMID- 16604972
TI  - Complete androgen insensitivity syndrome: report of a case with solitary pelvic
      kidney.
AB  - Complete androgen insensitivity syndrome, commonly known as the testicular
      feminization syndrome, is characterized by a 46, XY karyotype, bilateral testes,
      absent or hypoplastic Wolffian ducts, and female-appearing external genitalia
      with diminished axillary and pubic hair development. Although initial diagnosis
      in the child is difficult, the syndrome must be suspected after puberty if
      primary amenorrhea is present. Coexistence of genital defects with urologic
      abnormalities is expected in these cases because of close embryologic origin.
      However, unilateral renal agenesis with pelvic ectopia of the contralateral
      kidney does not seem so common. We report a case of testicular feminization
      syndrome with a solitary kidney located in bony pelvis on the left side.

PMID- 16604973
TI  - Computed tomography features of spontaneously perforated pyometra: a case report.
AB  - Spontaneous perforation of pyometra is an extremely rare emergent gynecologic
      disease. We report a 73-year-old woman with a spontaneously perforated pyometra
      presenting with acute abdomen in the emergency department. A dedicated computed
      tomography examination of the abdominal and pelvic regions revealed the
      diagnosis. The patient recovered well after surgical intervention and antibiotic
      treatment.

PMID- 16604974
TI  - An ethicist's commentary on the case of the academic veterinarian who returns to
      private practice.

PMID- 16604975
TI  - Diagnostic ophthalmology.

PMID- 16604976
TI  - Fostering a strong veterinary infrastructure for Canada: one practitioner's
      experience with bovine export certification.

PMID- 16604977
TI  - Primary orbital melanoma without ocular involvement in a Balinese cat.
AB  - A 6.5-year-old spayed female Balinese cat was diagnosed with a large and locally
      invasive primary orbital melanoma, without ocular involvement or detectable
      metastatic disease. Advanced imaging and immunohistochemical studies helped in
      obtaining the diagnosis. Because of advanced unresectable disease and ensuing
      poor quality of life, the cat was euthanized.

PMID- 16604978
TI  - Mycoplasma haemolamae infection in a 4-day-old cria: support for in utero
      transmission by use of a polymerase chain reaction assay.
AB  - Blood smear examination in a 4-day-old alpaca revealed massive erythrocyte
      parasitism by Mycoplasma haemolamae. Blood collected from both the nonparasitemic
      dam and the cria were positive for M. haemolamae by polymerase chain reaction
      (PCR) analysis. These findings suggest in utero transmission of M. haemolamae in
      camelids, even when the dam is not parasitemic.

PMID- 16604979
TI  - Analysis of a practice management computer software program for owner compliance
      with recall reminders.
AB  - The purpose of this study was to describe clients' level of compliance with
      reminders that are computer generated and to identify factors associated with
      owner response to a recall. Client response to a recall notice revealed that
      clients responded to reminders for vaccination about 3 times less often than for
      the other recall codes combined (dental procedures, laboratory tests, medical
      progress examinations, and neutering). These results suggest that veterinarians
      need to move away from annual vaccination reminders and toward the promotion of
      preventive veterinary services, such as annual wellness examinations, screening
      laboratory testing, and routine dental procedures. Once a practice has committed
      to and set up the required computer systems to promote preventive veterinary
      care, the stage is set for the implementation and monitoring of recommendations
      and reminders. This type of practice philosophy and marketing coincides perfectly
      with an approach to maximizing compliance in all aspects of veterinary medicine.

PMID- 16604980
TI  - Racing prognosis of horses following surgically repaired olecranon fractures.
AB  - Olecranon fracture is a common orthopedic problem in juvenile horses. Prognosis
      for complete fracture healing when various methods of internal fixation are used
      is good; however, the impact of olecranon fracture stabilization on the
      likelihood that foals will start on a racecourse is unknown. Medical records of
      foals undergoing internal fixation for an olecranon fracture were reviewed. The
      dam's foaling records were obtained and lifetime racing records were then
      retrieved for both the affected foals and 1 of their siblings. Twenty-two of 24
      repaired fractures healed completely, subsequently, 16 of the foals started in at
      least 1 race. Statistical calculations suggest that when compared with their
      siblings, the occurrence of olecranon factures requiring internal fixation in
      juvenile racehorses will not significantly reduce the likelihood that they will
      race; however, the siblings had significantly more lifetime race starts and
      higher career earnings.

PMID- 16604981
TI  - Ventricular septal defects in cattle: a retrospective study of 25 cases.
AB  - Clinical and complementary examination, pathological findings, and outcome were
      reviewed for 25 heifers diagnosed with ventricular septal defect (VSD). Age at
      presentation ranged from 36 h to 21 mo. The most common reasons for consultation
      were chronic respiratory problems (11 cases; 44%) or assessment of heart murmur
      (5 cases; 20%). A pansystolic murmur on the right thoracic side was audible in 20
      cases (80%). Pneumonia that interfered with adequate cardiac auscultation was
      found in 15 calves (60%). Echocardiography was useful in establishing the final
      diagnosis of VSD (sensitivity of 94%). Prognosis was poor: only 10 calves were
      discharged and no heifer out of the 6 cases for which follow-up information was
      available had a productive life in the herd. Inadequate reproductive performance
      was owners' most common complaint (4 of 6 heifers).

PMID- 16604982
TI  - Update on antimicrobial susceptibilities of bacterial isolates from canine and
      feline otitis externa.
AB  - The in vitro susceptibility of a total of 1819 bacterial isolates from canine and
      103 isolates from feline otitis externa cases to 13 antimicrobial drugs over a 5
      year period was evaluated. Among topically used drugs, 90% of isolates were
      susceptible to gentamicin. Susceptibility of Pseudomonas aeruginosa to gentamicin
      was 85%, and to polymyxin B 100%. For isolates other than the Pseudomonas sp.,
      susceptibility was highest to amoxicillin-clavulanic acid.

PMID- 16604983
TI  - A case of salinomycin intoxication in turkeys.
AB  - A flock of 4287 heavy hybrid turkey hens were accidentally fed broiler premix
      containing salinomycin sodium and suffered a 34.5% death loss. Measures taken to
      ensure food safety for the remaining flock and consumer food safety included feed
      record studies, on-farm veterinary consultation, diagnostic laboratory studies,
      and CgFARAD and CFIA consultation. The remaining turkeys were processed 3 weeks
      after the initial toxicosis with no evidence of lesions that would render the
      product unfit for human consumption.

PMID- 16604984
TI  - Guttural pouch mycosis in a 6-month-old filly.
AB  - A 6-month-old filly was presented with unilateral epistaxis. Based on clinical
      signs, endoscopic examination, and postmortem examination, guttural pouch mycosis
      was diagnosed. The young age of the filly and the fact that this was the 2nd
      diagnosis of guttural pouch mycosis on this farm was unusual.

PMID- 16604985
TI  - Radiation therapy for canine mast cell tumors.

PMID- 16604986
TI  - Lack of animal welfare assessment regarding trans-vaginal spaying of heifers.

PMID- 16604987
TI  - Managing inventory costs.

PMID- 16604988
TI  - Urology for the practitioner. Living up to the best tradition of our medical
      profession.

PMID- 16604989
TI  - Vesicoureteral reflux: diagnosis and management.
AB  - Vesicoureteral reflux is the retrograde passage of urine from the bladder into
      the ureter and kidneys during voiding. This commonly-treated entity is frequently
      managed by different disciplines that include Urology, Nephrology and Pediatrics.
      The pathophysiology of vesicoureteral reflux seems to be related to the valve
      mechanism of the ureterovesical junction. Abnormal location of the ureteral
      orifice is implicated in the short ureteral tunnel which in turn compromised the
      flap-valve mechanism. The grading of reflux is important since management depends
      on the severity according to a five grade system. At present, medical management
      using antibiotic prophylaxis has become well established for managing patients
      with low-grade reflux (grades I-III). Moderate reflux (grade III-IV) could be
      managed by surgery in case of breakthrough infections. Recommendations regarding
      the diagnosis and medical management remain complex and are continuously
      evolving. More frequently than not, treating pediatricians and urologists would
      have to make decisions by individualizing each patient and considering the
      likelihood that patient's reflux will resolve.

PMID- 16604990
TI  - The workup of microscopic and gross hematuria.
AB  - Based on the American Urological Association best practice policy statement, the
      workup of microscopic hematuria is summarized in the above algorithm (Fig. 1).
      The presence of gross hematuria is always an indication for prompt full
      investigation.

PMID- 16604991
TI  - Current imaging of solid renal masses.
AB  - More than 40% of solid renal masses are incidentally discovered by ultrasound
      examinations. Computed tomography (CT) remains the cornerstone investigation for
      characterization and assessment of the extent of renal tumors, it is
      complementary to ultrasound. MR imaging is an adjunctive method reserved as a
      problem-solving technique for indeterminate masses by ultrasound and CT. PET-CT
      has a great potential role in the staging of renal cancer.

PMID- 16604992
TI  - Novel concepts in the treatment of localized renal cell carcinoma.
AB  - The understanding of renal cell carcinoma has undergone significant advances in
      the past several years. These have included advances in imaging procedures and
      surgical approaches, allowing for more precise staging, and individualized
      approaches to therapy. Furthermore, there has been an increase in the diagnosis
      of incidental tumors and currently the majority of RCCs are incidentally
      diagnosed on routing imaging procedures. In this manuscript, we review the
      surgical options for renal cell carcinoma with specific emphasis on the algorithm
      for approaching these tumors, in order to ensure maximal cancer specific
      survival, without threatening the overall renal function.

PMID- 16604993
TI  - Update on Wilms' tumor in children.
AB  - Although rare, Wilms' tumor is the most common primary renal malignancy in
      children and is associated with a number of congenital anomalies and documented
      syndromes. Appropriate laboratory, radiologic and pathologic investigations are
      necessary components of the evaluation of children with suspected Wilms' tumor.
      This provides accurate diagnosis and subsequent staging; information which is
      essential to generate a multidisciplinary treatment plan utilizing surgery,
      chemotherapy and radiotherapy. Patients treated for Wilms' tumor as children must
      continue to be monitored for possible long-term sequelae as adults including
      secondary malignancies as well as treatment-related toxicity.

PMID- 16604994
TI  - Nonseminomatous testicular cancer.
AB  - Testicular cancer is the most common solid malignancy in young men between the
      ages of 20 and 40 years. Its incidence is increasing worldwide. The success
      achieved in its treatment has not been seen in any other cancer. This
      communication will present some of the controversies in the management of
      nonseminomatous germ cell tumors, the changes that were introduced over the last
      two decades to decrease the toxicity from treatment and will discuss the most up
      to-date treatment of every clinical stage of the disease.

PMID- 16604995
TI  - Prostate cancer: diagnostic and therapeutic strategies with emphasis on the role
      of PSA.
AB  - Prostate cancer is the most common cancer in man and the second most common cause
      of death. The disease is uniquely heterogeneous, and includes tumors with
      moderate or full differentiation that could progress rather slowly, and tumors
      with poor differentiation that could have a rapid growth and extensive spread
      beyond the confines of the prostate. In the latter group of patients, and if they
      are not treated, the cancer becomes incurable and the long-term survival is
      compromised. The commonly accepted strategy among urologists at present is aimed
      at early detection of prostate cancer in order to provide curative local therapy.
      The recognition of prostate specific antigen (PSA) as a serum marker specific for
      prostate cancer has made this strategy possible. We herein provide an overview on
      the contemporary diagnostic and therapeutic strategies for prostate cancer, with
      emphasis on the role of prostate PSA. We also discuss the therapeutic options for
      localized disease.

PMID- 16604996
TI  - Role of dietary modification and vitamins in prostate cancer.
AB  - Prostate cancer incidence and nutrition are closely connected and show large food
      related differences. Lowest cancer incidence in Asian countries is observed under
      low-calorie, soy-based food. Mediterranean nutrition has cancer protective
      components (fruit, vegetables, oil, seafood). The highest cancer incidence in the
      United States goes along with high-calorie food, red meat and fat ingestion.
      Changes in lifestyle and nutrition can influence the cancer risk. Dietary
      supplements and vitamins are in wide use and part of a complementary and
      alternative medicine.

PMID- 16604997
TI  - Superficial bladder cancer epidemiology, diagnosis and management.

PMID- 16604998
TI  - Surgical adrenal diseases.
AB  - There are four adrenal disorders in which surgery is the treatment of choice:
      pheochromocytoma, Cushing's syndrome due to ACTH-independent adrenal disease
      (adenoma, carcinoma or autonomous hyperplasia), primary aldosteronism due to an
      adrenal adenoma and some adrenal non-functional "incidentilomas". In all four
      categories, the optimal result of surgical intervention depends on the following
      factors: 1. Definitive diagnosis by accurate biochemical assessment of the
      functional status of the adrenal lesion. 2. Precise localization of the lesion
      using simple routine as well as advanced imaging techniques. 3. Adequate
      preoperative preparation and intraoperative monitoring. 4. Close immediate and
      long-term postoperative follow-up. In this review, the above factors are briefly
      summarized for each of the four disorders. A small proportion of adrenal lesions
      requiring surgery are bilateral and in such situations, special intra- and
      postoperative care should take into consideration the need for appropriate gluco
      corticoid and mineralo-corticoid replacement. The advent of laparoscopic surgery
      has served to reduce the postoperative morbidity of adrenal surgery and is
      becoming increasingly the procedure of choice except for large lesions (> 8 cm in
      diameter).

PMID- 16604999
TI  - Dermatology for the urologist.
AB  - Dermatoses of the male genital area are widely diverse clinically and
      etiologically. Both dermatologists and urologists are involved in diagnosing and
      treating those dermatoses. This article will focus mainly on the important or
      commonly encountered entities classified according to their etiology as
      infectious, inflammatory, autoimmune, vascular, nervoid or other.

PMID- 16605000
TI  - [Science of nutrition: past, present, future].
AB  - The article describes the history of development of science of nutrition in
      Russia, the history of creating and development of Institute of Nutrition RAMS.

PMID- 16605001
TI  - [Resistant starches. Part 1. General description and physiologic aspects].
AB  - This paper the recent data related to useful nutritional properties of resistant
      starches which combine the functional features of food fibers and prebiotics. The
      low glycaemic index of resistant starches, as well as their specific way of
      metabolism in gastrointestinal tract resulting in production of short-chain fatty
      acids in large intestine is discussed. The potential medicinal and prophylactic
      benefits of resistant starches to some disasters are described. The important
      value of resistant starches in nutrition.

PMID- 16605002
TI  - [Fat and content of yakutan horse fat tissue].
AB  - The gas chromatography method the fat acid content of the young Yakut horse meat
      fat tissue lipids was studied in relation to the age group, various parts of the
      body and anatomic topographic location of the fat/It was determined that the of
      sixth-month young horse is the source of the PUFA omega-3 that allows to
      recommend horse meat as a dietary product for atherosclerosis prevention. By
      medial chain fat content the lipids of the 6 month young horses are close to the
      lipids of milk fat.

PMID- 16605004
TI  - [Result of anthropometric investigation of patients with obesity and
      cardiovascular pathology].
AB  - Examinations of patients with obesity and cardiovascular pathology were taken
      using anthropometric method. Specialities of their actual diet were taken into
      account, using computer program based on frequency method. As a result, new data
      has been obtained, which shows that a violation in diet has an effect on
      anthropometric status of patients.

PMID- 16605003
TI  - [Modelling of arterial hypertension, biochemical fat and carbohydrate metabolism
      index in laboratory animals at simultaneous injecting insulin and cholesterol].
AB  - We studied status of arterial hypertension, biochemical fat and carbohydrate
      metabolism index in blood in male rabbits as a result of hyperchlesterolemia and
      hyperinsulinemia. We found that, chronic injection of insulin to rabbits with
      high serum cholesterol can increase level of arterial blood pressure.

PMID- 16605005
TI  - [Sanitary-bacteriologal examination of liquids in Tbilisi].
AB  - Sanitary and Hygiene examination of light drinks such are: kvass, beer, fruit,
      mineral and other drinks, juices and none standardized drinks in Tbilisi in 2000
      2004 showed that this products typically, mostly produced by small commercial
      enterprises, are typically produced out of sanitary-epidemiological and sanitary
      hygiene norms and regulations. Working out of sufficient control-monitoring
      mechanism will improve the situation.

PMID- 16605006
TI  - [Epidemiological research of the nutrition men of Kabardino-Balkaria: social
      economic and medical aspects, national peculiarities].
AB  - The epidemiological research of the nutrition status and the prevalance of the
      main risk factors of cardiovascular deseases among men aged 35-60 was held in
      Kabardino-Balkaria. The comporative analyse of consumption of the main groups of
      foods in the families of the men with different level of income and treatment of
      nutrients, energy and micronutrients. The results showd the connection between
      the studied parameters and economical status of the examined men. The necessity
      of development of nutrition support in low-income people and teaching the whole
      population principles of healthy nutrition with the consideration of regional and
      national peculiarities of KBR was shown.

PMID- 16605007
TI  - [Study of natural stability microorganism of polycomponent starter for the milk
      product to ten antibiotics].
AB  - Microorganism natural stability of three different starters to ten antibiotics
      was studied. The establishment, At was defined that polycomponent starter on the
      base of lacto- and bifidobacteria has the most stability to antibiotics. The use
      of this starter in the production of milk products will allow to have strongly
      pronounced therapeutic effect and to enlarge the range of probiotic milk products
      for people of different age.

PMID- 16605008
TI  - [Status and prospects of development of legislative base for food supplements
      turnover in some countries].
AB  - The articles contains the results of modern legislative base, regulating food
      supplements turnover in the USA, some European contries, as well as passed by
      European Parliament.

PMID- 16605009
TI  - [Functional meat food in atherosclerosis prevention].
AB  - Diet is effective method of atherosclerosis prevention. Traditional meet food
      consists the high cholesterol level. It was shown that cholesterol level is
      considerable low in new functional meet food. Such food-stuff may be use for the
      atherosclerosis prevention.

PMID- 16605010
TI  - [The use of flavolignans of "Silybum marianum (L.) Gaertn." to create a new fat
      product--fortified butter].
AB  - The results of study on substantiating the possibilities of the use of
      flavolignans of Silybum marianum (L.) Gaertn. with a purpose to create a new fat
      product--butter fortified by an "Liguid extract Silybum marianum (L.) Gaertn."
      are being discussed. Slowdown of peroxidation process is revealed in fortified
      butter in comparison with ordinary butter. With the help of spectrometry method
      higher content of flavolignans was deteeted in fortified butter (converting to
      silibin--the main component of "Liguid Exstract Silybum marianum (L) Gaertn"),
      what allows to speak about increase of its potential therapeutic effect.

PMID- 16605011
TI  - Parathion degradation and toxicity reduction in solar photocatalysis and
      photolysis.
AB  - The solar photocatalytic degradation of methyl parathion was investigated using a
      circulating TiO2/solar light reactor. Under solar photocatalysis condition,
      parathion was more effectively degraded than solar photolysis and TiO2-only
      conditions. With solar photocatalysis, 20 mg/L of parathion was completely
      degraded within 60 min with a TOC decrease of 63% after 150 min. The main ionic
      byproducts during photocatalysis recovered from parathion degradation were mainly
      as NO3-, NO2- and NH4+, 80% of the sulphur as SO4(2-), and 5% of phosphorus as
      PO4(3-). The organic intermediates 4-nitrophenol and methyl paraoxon were also
      identified, and these were further degraded in solar photocatalytic condition.
      Two different bioassays (Vibrio fischeri and Daphnia magna) were used to test the
      acute toxicity of solutions treated by solar photocatalysis and photolysis. The
      Microtox test using V. fischeri showed that the toxicity expressed as EC50 (%)
      value increased from 5.5% to >82% in solar photocatalysis, indicating that the
      treated solution is non-toxic, but only increased from 4.9 to 20.5% after 150 min
      in solar photolysis. The acute toxicity test using D. magna showed that EC50 (%)
      increased from 0.05 to 1.08% under solar photocatalysis, but only increased to
      0.12% after 150 min with solar photolysis, indicating the solution is still
      toxic. The pattern of toxicity reduction parallels the decrease in TOC and the
      parathion concentrations.

PMID- 16605012
TI  - Use of immobilised bacteria for the wastewater treatment--examples from the sugar
      industry.
AB  - This work focuses on the implementation of high performance systems to the
      wastewater treatment of sugar factories. For this purpose, systems with
      immobilised bacteria were studied. For the hydrolysis of organic matter and
      denitrification, fluidized bed reactors were used. The nitrification was studied
      with an airlift reactor system. Both hydrolysis and nitrogen elimination were
      investigated on laboratory and pilot scales in sugar factories. Although with
      porous materials higher biomass concentrations are attainable for the hydrolysis
      (up to 55 kg/m3), for economical reasons sand was used (22.5 kg/m3) for the pilot
      scale-study. With a pilot-scale reactor (volume 1 m3) the maximum sucrose
      conversion rate achieved with sand in the first campaign was 52 kg/(m3 d). For
      the nitrogen elimination on the pilot scale, a system with denitrification and
      nitrification was combined. The highest performance for the nitrification
      (reactor volume: 0.68 m3) with pumice as support material was 1.2 kg NH4-N/(m3
      d), limiting the whole system. The denitrification rate (reactor volume: 0.12 m3)
      was four times higher (3.5-5 kg NO3-N/(m3 d). Rules of the modelling of the
      system are discussed.

PMID- 16605013
TI  - Pretreatment and biotreatment of saline industrial wastewaters.
AB  - Wastewater from an Akzo Nobel production site contains more than 50 g/l total
      dissolved salts, mainly chlorides and sulphates, and is currently being treated
      after 10-20 x dilution. Biological treatment of undiluted or less diluted
      wastewater is very desirable for environmental and economic reasons.
      Possibilities were investigated in laboratory scale reactors to treat this highly
      saline and high strength wastewater aerobically, either after long adaptation or
      after removing part of the salts by a pretreatment. Adaptation and selection from
      mixed activated sludge populations took approximately 40 days to finally achieve
      a COD removal in aerobic treatment of 55-65% at two times dilution (11-16 g/l
      chloride and 5-7 g/l sulphate). Undiluted wastewater was not treatable. A higher
      removal percentage (> 80%) was possible at the original high salt concentration
      only when the sludge load was limited to approximately 0.4-0.5 kg COD/kg
      sludge/day. A longer adaptation time was required. Nanofiltration (NF) and
      crystallization could be used as a pretreatment to remove and recover up to 80%
      of the sulphate in the form of crystallized Glauber salt. Recovery strongly
      depended on the sulphate and chloride concentration in the NF concentrate and on
      crystallization temperature. The salt (sulphate) reduction through the NF
      improved the removal efficiency of a consecutive biotreatment only at a
      relatively low chloride level, demonstrating that the combination of
      nanofiltration-crystallization-aerobic biodegradation is less feasible for very
      saline wastewaters. Anaerobic pretreatment of saline waters turned out to be
      rather sensitive to high salinities. Only wastewater diluted to 10 g/l chloride
      could be treated well: sulphate concentration decreased by 80% and COD by 40%.
      Removal efficiencies of the combined anaerobic-aerobic treatment were
      approximately 80-85%, proving that this was a feasible route for 2-3 x diluted
      wastewater. The study has shown that several alternatives are available for
      treatment of the very saline wastewaters at a much lower degree of dilution than
      currently practiced.

PMID- 16605014
TI  - On-site treatment of high-strength alcohol distillery wastewater by a pilot-scale
      thermophilic multi-staged UASB (MS-UASB) reactor.
AB  - A pilot-scale multi-staged UASB (MS-UASB) reactor with a working volume of 2.5 m3
      was operated for thermophilic (55 degrees C) treatment of an alcohol distillery
      wastewater for a period of over 600 days. The reactor steadily achieved a super
      high rate COD removal, that is, 60 kgCOD m(-3) d(-1) with over 80% COD removal.
      However, when higher organic loading rates were further imposed upon the reactor,
      that is, above 90 kgCOD m(-3) d(-1) for barely-based alcohol distillery
      wastewater (ADWW) and above 100 kgCOD m(-3) d(-1) for sweet potato-based ADWW,
      the reactor performance somewhat deteriorated to 60 and 70% COD removal,
      respectively. Methanogenic activity (MA) of the retained sludge in the
      thermophilic MS-UASB reactor was assessed along the time course of continuous run
      by serum-vial test using different substrates as a vial sole substrate. With the
      elapsed time of continuous run, hydrogen-utilizing MA, acetate-utilizing MA and
      propionate-fed MA increased at maximum of 13.2, 1.95 and 0.263 kgCOD kgVSS(-1) d(
      1), respectively, indicating that propionate-fed MA attained only 1/50 of
      hydrogen-utilizing MA and 1/7 of acetate-utilizing MA. Since the ADWW applied
      herewith is a typical seasonal campaign wastewater, the influence of shut-down
      upon the decline in sludge MA was also investigated. Hydrogen-utilizing MA and
      acetate-utilizing MA decreased slightly by 3/4, during a month of non-feeding
      period, whereas propionate-fed MA were decreased significantly by 1/5. Relatively
      low values of propionate-fed MA and its vulnerability to adverse conditions
      suggests that the propionate degradation step is the most critical bottleneck of
      overall anaerobic degradation of organic matters under thermophilic condition.

PMID- 16605015
TI  - Membrane bioreactors in industrial wastewater treatment--European experiences,
      examples and trends.
AB  - In wastewater treatment, micro- and ultra-filtration membranes are used for the
      separation of the activated sludge (biomass) from the treated water. This offers
      the advantages of a complete removal of solids and bacteria, as well as most of
      the viruses, namely those attached to the suspended solids. Compared to the
      conventional activated sludge process (CAS) this technology allows a much higher
      biomass concentration (MLSS) whereby the reactor volume and the footprint
      decreases. With increasing MLSS, the viscosity of the sludge increases, which
      leads to reduced oxygen transfer rates. Depending on the type of membrane and
      membrane module, the pre-treatment has to be more sophisticated to prevent
      clogging and sludging of the modules. Due to fouling and scaling, the flux
      through the membranes will decrease with time. The decrease depends on the water
      quality as well as on the measurements taken to minimize fouling. Mainly, three
      strategies are available: lowering the flux, increasing the "crossflow" and
      cleaning of the membranes. Different strategies including backwash and chemical
      cleaning "in situ", "on air" and "ex situ" can be applied. It has been proven
      more effective to apply preventive regular cleaning. Besides the energy demand
      for oxygen supply--which is typically in the range of 0.3 kWh/m3 for municipal
      wastewater--the energy for fouling prevention is substantial. Immersed membranes
      need approximately 0.4 to 1 kWh/m3 for the coarse bubble aeration, whereas
      tubular modules require 1 to 4 kWh/m3 pump energy. For proper design of
      industrial wastewater treatment, the verification of applicability and the
      development of adequate cleaning strategies, it is a precondition to run pilot
      tests for a sufficient period of time with the wastewater to be treated. More
      than 100 industrial wastewater treatment membrane bioreactors (MBR) are in
      operation in Europe. Data of three case studies for a sewage sludge dewatering
      plant in UK (12,000 m3/d), a plant for the treatment of pharmaceutical wastewater
      in Germany (3600 m3/d), as well for revamping of an chemical WWTP >2000 m3/d in
      Italy, are given. MBRs will be used in future wherever high quality effluent is
      required, because of a sensitive receiving water body or due to the fact of water
      reuse as process water. MBRs are a perfect pre-treatment in industrial
      applications when further treatment with nanofiltration or reverse osmosis is
      considered. The technique is advanced and can be applied both in municipal and
      industrial wastewater treatment. Higher operational costs must be balanced by
      superior effluent quality.

PMID- 16605016
TI  - Responsible development of nanotechnologies for water and wastewater treatment.
AB  - Emerging technologies, including nanotechnologies, affect the social, economic,
      and environmental dimensions of our world, often in ways that are entirely
      unanticipated. There is considerable effort underway to explore uses of
      nanomaterials in applications such as membrane separations, catalysis,
      adsorption, and analysis with the goal of better protecting environmental
      quality. Along with the growth of a nanochemistry industry there is also the need
      to consider impacts of nanomaterials on environment and human health.

PMID- 16605017
TI  - Development of MBR with reduced operational and maintenance costs.
AB  - To reduce MBR O&M costs, a new MBR process that conducts efficient simultaneous
      biological nitrogen and phosphorus removal (BNR) was developed. In the
      development of this process, various approaches were taken, including reduction
      of power demand, chemical consumption and sludge disposal costs. To address power
      demand reductions, air supply requirements for membrane cleaning were reduced.
      The process adopted an improved membrane that requires less air for cleaning than
      conventional membranes. It also introduced cyclic aeration, which alternately
      supplies washing air to the two series of membrane units. Adoption of biological
      phosphorus removal eliminated chemical costs for phosphorus removal and
      contributed to the reduction of sludge disposal costs. By combining these
      technologies, compared to conventional MBR processes, an approximately 27%
      reduction in O&M costs was achieved.

PMID- 16605018
TI  - Performance of membrane bioreactors used for the treatment of wastewater from the
      chemical and textile industries.
AB  - Within the scope of the study, nine waste waters from the chemical and textile
      industries were treated in bench-scale (laboratory scale) and small-scale (pilot
      scale) membrane bioreactors. Depending on wastewater characteristics, the
      resulting performance varied significantly. It was observed that MBR
      effectiveness was determined primarily by the degree of biodegradability of the
      wastewater. In the course of several months of operation, no significant changes
      associated with the complete retention of the biomass by the membranes were
      observed. In some cases, it was possible to improve effluent quality by using
      smaller molecular separation sizes. The flux performance of the membrane modules
      was dependent on wastewater composition. Occasionally, non-degradable
      macromolecular substances concentrated in the bioreactor, resulting in strongly
      reduced filterability and flow performance of the membrane modules, consequently
      also reducing the economic viability of the process. The results demonstrate that
      wastewater-specific pilot tests are absolutely necessary, in particular if the
      technology is to be used for new applications.

PMID- 16605019
TI  - Domestic wastewater treatment with a small-scale membrane bioreactor.
AB  - A small-scale membrane plant for treating the domestic wastewater of a four
      person household is presented. The membrane bioreactor has been in operation for
      6 months and achieves elimination rates of 90, 95 and 80% for total organic
      carbon, chemical oxygen demand and total nitrogen, respectively. Only a small
      amount sludge is produced. The permeate is reused for flushing toilets and has a
      yellowish colour. After investigations of the effluent quality, decolourisation
      of the permeate, energy efficiency and control strategies in the first year,
      urine will be treated separately in an automated precipitation reactor where
      struvite is produced to improve the overall phosphate removal of the plant.

PMID- 16605020
TI  - Modelling of wastewater treatment plants--how far shall we go with sophisticated
      modelling tools?
AB  - Several levels of complexity are available for modelling of wastewater treatment
      plants. Modelling local effects rely on computational fluid dynamics (CFD)
      approaches whereas activated sludge models (ASM) represent the global
      methodology. By applying both modelling approaches to pilot plant and full scale
      systems, this paper evaluates the value of each method and especially their
      potential combination. Model structure identification for ASM is discussed based
      on a full-scale closed loop oxidation ditch modelling. It is illustrated how and
      for what circumstances information obtained via CFD (computational fluid
      dynamics) analysis, residence time distribution (RTD) and other experimental
      means can be used. Furthermore, CFD analysis of the multiphase flow mechanisms is
      employed to obtain a correct description of the oxygenation capacity of the
      system studied, including an easy implementation of this information in the
      classical ASM modelling (e.g. oxygen transfer). The combination of CFD and
      activated sludge modelling of wastewater treatment processes is applied to three
      reactor configurations, a perfectly mixed reactor, a pilot scale activated sludge
      basin (ASB) and a real scale ASB. The application of the biological models to the
      CFD model is validated against experimentation for the pilot scale ASB and
      against a classical global ASM model response. A first step in the evaluation of
      the potential of the combined CFD-ASM model is performed using a full scale
      oxidation ditch system as testing scenario.

PMID- 16605021
TI  - Modification of ASM3 for the determination of biomass adsorption/storage capacity
      in bulking sludge control.
AB  - The selector activated sludge (SAS) systems are known to prevent excessive growth
      of filamentous microorganisms responsible for bulking sludge, but these systems
      were hardly ever modelled. This study aimed to develop a model capable of
      predicting rapid substrate removal in the SAS systems. For this purpose, the
      Activated Sludge Model No. 3 (ASM3) was extended with three processes
      (adsorption, direct growth on the adsorbed substrate under aerobic or anoxic
      conditions). The modified ASM3 was tested against the results of batch
      experiments with the biomass originating from two full-scale SAS systems in
      Germany. The endogenous biomass was mixed with various readily biodegradable
      substrates (acetate, peptone, glucose and wastewater) and the utilisation of
      substrate (expresses as COD) and oxygen uptake rates (OURs) were measured during
      the experiments. In general, model predictions fitted to the experimental data,
      but a considerable number of kinetic (5) and stoichiometric (2) parameters needed
      to be adjusted during model calibration. The simulation results revealed that
      storage was generally a dominating process compared to direct growth in terms of
      the adsorbed substrate utilisation. The contribution of storage ranged from 65
      71% (Plant A) and 69-92% (Plant B).

PMID- 16605022
TI  - Development and exploitation of a multipurpose CFD tool for optimisation of
      microbial reaction and sludge flow.
AB  - A numerical analysis technique for optimisation of microbial reaction and sludge
      flow has been developed in this study. The technique is based on the 3D
      multiphase Navier-Stokes solver with turbulence models. In order to make
      numerical analyses of the total processes in wastewater treatment plants
      possible, four numerical models, the microbial reaction model, a sludge settling
      model, oxygen mass transfer model from coarse bubbles, and a model from fine
      bubbles, are added to the solver. All parameters included in those models are
      calibrated in accordance with experimental results, and good agreements between
      calculated results and experimental results are found. Finally, this study shows
      that the numerical technique can be used to optimise wastewater treatment plants
      with an example of the operational optimisation of an intermittent agitation in
      anoxic reactors by coarse bubbles. With a proper appreciation of its limit and
      advantages, the exploitation of the CFD efficiently leads us to the right
      direction even though it is not quantitatively perfect.

PMID- 16605023
TI  - Activated sludge modelling: past, present and future.
AB  - Model complexity in activated sludge modelling has increased over 30 years in
      parallel with the computational power of computers. Today, the complexity of
      biokinetics has reached a practical limit. Future advances may be in the
      direction of enhanced spacial resolution (CFD, single organisms) respectively, in
      repetitive computations (MC simulation, parameter identification). Further model
      development may be in niches such as population dynamics, micropollutants, etc.

PMID- 16605024
TI  - Plant-wide control: dream, necessity or reality?
AB  - Instrumentation, control and automation (ICA) are key technologies in modern
      water and wastewater systems. Despite the variability of the influents the system
      outputs have to be satisfactory. Economic realities and new water directives
      encourage the application of ICA to make a maximum use of plant and other storage
      capacities. The final goal of protecting the environmental resources necessitates
      an integrated view of several interdependent systems, including the collection,
      transport and treatment processes. In this integrating development ICA will be a
      decisive technology.

PMID- 16605025
TI  - Phosphorus removal and recovery from wastewater by tobermorite-seeded
      crystallisation of calcium phosphate.
AB  - Investigations were focused on the development of a technology for phosphorus (P)
      recovery straight from wastewater. Facing the finiteness of the natural resources
      of this essential nutrient, the declared goal must be the sustainable use of
      available phosphorus sinks such as wastewater treatment plants (WWTP) for the
      generation of P rock substitutes. A feasible method for simultaneous elimination
      and recovery of phosphorus from wastewater proved to be the P-RoC process - the
      phosphorus recovery from wastewater by induced crystallisation of calcium
      phosphate, applying tobermorite-rich waste compounds of the construction
      industry. The experiments were performed in fixed bed-, stirred- and expanded bed
      reactors in laboratory--as well as in pilot-scale experiments. The efficiency and
      longevity of the P-RoC process was determined by the supply of Ca ions and the
      initial P concentration. Total P (P-tot) contents in the generated
      crystallisation products of up to 13% P-tot (30% P2O5) were achieved.
      Mineralogical investigations proved the formation of a hydroxy-apatite-(HAP)-like
      coating onto the seed material's surface. Reuse options for the generated
      crystallisation products, such as substitute for phosphate rock or as new
      fertiliser, were assessed.

PMID- 16605026
TI  - Treatment of source-separated urine by a combination of bipolar electrodialysis
      and a gas transfer membrane.
AB  - Urine contains nutrients which can be applied usefully as a fertiliser in
      agriculture, but the relatively high pH can lead to ammonia evaporation.
      Electrodialysis with bipolar membranes was combined with an additional mass
      transfer unit in order to render a product containing ammonium and phosphate at a
      low pH. In one case, the additional mass transfer unit consisted of bubble
      columns placed in acid and basic concentrate streams, connected with a
      circulating gas phase. In the other case, the unit consisted of a gas-filled
      (hydrophobic) membrane placed in between the circulating acid and basic
      concentrate streams. The results showed that ammonia was transferred through the
      gas phase, but also carbonate, which is present in stored urine originating from
      the hydrolysis of urea. Although the pH in the product stream decreases
      initially, it rises above pH 7 at longer operation times. This pH increase can be
      attributed to a combination of proton compensating effects. The use of ammonia
      selective membranes for the transfer into the acid concentrate could provide a
      solution to generate an ammonium phosphate product at low pH and high recoveries.

PMID- 16605027
TI  - High-rate nitrification using aerobic granular sludge.
AB  - The performance of nitrifying granules, which had been produced in an aerobic
      upflow fluidised bed (AUFB) reactor, was investigated in various types of ammonia
      containing wastewaters. When pure oxygen was supplied to the AUFB reactor with a
      synthetic wastewater containing a high concentration of ammonia (500 g-N/m3), the
      ammonia removal rate reached 16.7 kg-N/m3/day with a sustained ammonia removal
      efficiency of more than 80%. The nitrifying granules possessing a high settling
      ability could be retained with a high density (approximately 10,000 g-MLSS/m3) in
      a continuous stirring tank reactor (CSTR) even under a short hydraulic retention
      time (44 min), which enabled a high-rate and stable nitrification for an
      inorganic wastewater containing low concentrations of ammonia (50 g-N/m3).
      Moreover, the nitrifying granules exhibited sufficient performance in the
      nitrification of real industrial wastewater containing high concentrations of
      ammonia (1000-1400 g-N/m3) and salinity (1.2-2.2%), which was discharged from
      metal-refinery processes. When the nitrifying granules were used in cooperation
      with activated sludge to treat domestic wastewater containing organic pollutants
      as well as ammonia, they fully contributed to nitrification even though a part of
      activated sludge adhered onto the granule surfaces to form biofilms. These
      results show the wide applicability of nitrifying granules to various cases in
      the nitrification step of wastewater treatment plants.

PMID- 16605028
TI  - Where is biological nutrient removal going now?
AB  - With more than 30 years of experience multiple options exist for removal of
      nitrogen and phosphorus from wastewater. Communities that were exempt from
      nutrient removal for many years must now comply with imposed nutrient limits, and
      in areas where technology-based nutrient limits have been in place communities
      are now faced with more stringent mass-based limits that are becoming more
      difficult to meet as their populations increase. Recent efforts in the industry
      have been focused on getting more out of existing plants, or in many cases where
      land is not available, in intensifying existing processes to increase capacity
      and/or level of treatment. This paper will discuss some of these methods and the
      general direction in which biological nutrient removal is developing to address
      these new challenges.

PMID- 16605029
TI  - Low effluent nutrient technologies for wastewater treatment.
AB  - The USEPA (2001) water quality nutrient criteria will have a significant impact
      on water pollution control industry due to stringent N and P requirements. This
      paper presents an update of findings on successful total N (TN) and total P (TP)
      technologies being implemented at existing wastewater treatment plants (WWTP) to
      achieve low TN and TP effluents and some key challenges in achieving lower
      levels. Plants consistently achieving <5 mg TN/L and < 0.5 mg TP/L were
      identified from a worldwide literature search and plant data collection.
      Technology gaps and research needs to improve successful technologies to achieve
      very low TN and TP effluents are summarised in this paper. The dissolved and
      colloidal organic N have been identified as major challenges in achieving very
      low levels of TN. Technical and economic challenges to achieve very low TP
      effluents include alkalinity deficiency, high chemical usage, high sludge
      production and lack of sufficient influent BOD for biological P uptake.

PMID- 16605030
TI  - Membrane chemical reactor (MCR) combining photocatalysis and microfiltration for
      grey water treatment.
AB  - Urban water recycling is now becoming an important issue where water resources
      are becoming scarce. This paper looks at reusing grey water; the preference is
      treatment processes based on biological systems to remove the dissolved organic
      content. Here, an alternative process, photocatalysis is discussed as it is an
      attractive technology that could be well-suited for treating the recalcitrant
      organic compounds found in grey water. The photocatalytic process oxidises
      organic reactants at a catalyst surface in the presence of ultraviolet light.
      Given enough exposure time, organic compounds will be oxidized into CO2 and
      water. The best contact is achieved in a slurry reactor but a second step to
      separate and recover the catalyst is need. This paper discusses a new membrane
      chemical reactor (MCR) combining photocatalysis and microfiltration for grey
      water treatment.

PMID- 16605031
TI  - Leachate detoxification by combination of biological and TiO2-photocatalytic
      processes.
AB  - Landfill leachates are a problematic wastewater due to their variable
      concentration, volume changing in time and presence of refractory and hazardous
      components. In this paper, the results of a new approach to photocatalysis
      assisted by biological process for the detoxification of stabilised landfill
      leachate are presented. The biologically pre-treated leachate still contained a
      significant amount of non-biodegradable COD and TOC amounting to 500 and 200
      mg/L, respectively. The 300 min of photocatalytic treatment (UVC/TiO2) brought
      about a significant decrease in more than 80% refractory organics remaining in
      leachate. The effect of pH and catalyst loading on mineralisation, colour removal
      rate and biodegradability (BOD/COD) improvement in the photoreactor were
      discussed. The bio-accessibility of formed photocatalytic oxidation intermediates
      was confirmed by oxygen uptake rate (OUR) measurements. Consequently, a part of
      COD was successfully removed in post-biological treatment.

PMID- 16605032
TI  - Model-based evaluation of struvite recovery from an in-line stripper in a BNR
      process (BCFS).
AB  - Phosphate removal and recovery can be combined in BNR processes. This may be
      realised by struvite precipitation from the supernatant of the sludge in
      anaerobic compartments. This can be beneficial for either improving bio-P removal
      effluent quality or lowering the influent COD/P ratio required for bio-P removal.
      For this reason, a patented BNR process, BCFS, was developed and applied in The
      Netherlands. Several questions relating to P-recovery and behaviour of the system
      remain unclear and need to be ascertained. For this purpose, a modelling
      technique was employed in this study. With the help of a previous developed model
      describing carbon oxidation and nutrient removal, three cases were fully
      simulated. The simulations demonstrated that there was an optimal stripping flow
      rate and P-recovery would increase in costs and bio-P activity might be
      negatively affected due to decreased bio-P efficiency if this value was exceeded.
      The simulations indicated that the minimal COD(biod)/P ratio required for the
      effluent standard (1 g P/m3) could be lowered from 20 to 10 with 36% of P
      recovery. A simulation with dynamic inflow revealed that the dynamic influent
      loads affected slightly the anaerobic supernatant phosphate concentration but the
      effluent phosphate concentration would not be affected with regular P-recovery.

PMID- 16605033
TI  - Copper and zinc removal from roof runoff: from research to full-scale adsorber
      systems.
AB  - Large, uncoated copper and zinc roofs cause environmental problems if their
      runoff is infiltrated into the underground or discharged into receiving waters.
      Since source control is not always feasible, barrier systems for efficient copper
      and zinc removal are recommended in Switzerland. During the last few years,
      research carried out in order to test the performance of GIH-calcite adsorber
      filters as a barrier system. Adsorption and mass transport processes were
      assessed and described in a mathematical model. However, this model is not
      suitable for practical design, because it does not give explicit access to design
      parameters such as adsorber diameter and adsorber bed depth. Therefore, for e.g.
      engineers, an easy to use design guideline for GIH-calcite adsorber systems was
      developed, mainly based on the mathematical model. The core of this guideline is
      the design of the depth of the GIH-calcite adsorber layer. The depth is
      calculated by adding up the GIH depth for sorption equilibrium and the depth for
      the mass transfer zone (MTZ). Additionally, the arrangement of other adsorber
      system components such as particle separation and retention volume was considered
      in the guideline. Investigations of a full-scale adsorber confirm the successful
      application of this newly developed design guideline for the application of GIH
      calcite adsorber systems in practice.

PMID- 16605034
TI  - Combining UASB and the "fourth generation" down-flow hanging sponge reactor for
      municipal wastewater treatment.
AB  - A "fourth generation" down-flow hanging sponge (DHS) Reactor has been developed
      and proposed as an improved variant of post-treatment system for UASB treating
      domestic wastewater. This paper evaluates the potential of the proposed
      combination of UASB and DHS as a sewage treatment system, especially for
      developing countries. A pilot-scale UASB (1.15 m3) and DHS (0.38 m3; volume of
      sponge) was installed in a municipal sewage treatment site and constantly
      monitored for 2 years. UASB was operated at an HRT of 6 h corresponding to an
      organic load of 2.15 kg-COD/m3 per day. Subsequently, the organic load in DHS was
      2.35 kg-COD/m3 per day, operated at an HRT of 2 h. Organic removal by the whole
      system was satisfactory, accomplishing 96% of unfiltered BOD removal and 91% of
      unfiltered COD removal. However, nitrification decreased from 56% during the
      startup period to 28% afterwards. Investigation on DHS sludge was made by
      quantifying it and evaluating oxygen uptake rates with various substrates.
      Average concentration of trapped biomass was 26 g-VSS/L of sponge volume,
      increasing the SRT of the system to 100-125 d. Removal of coliforms obtained was
      3-4 log10 with the final count of 10(3) to 10(4) MPN/100 ml in DHS effluent.

PMID- 16605035
TI  - The membrane biofilm reactor: the natural partnership of membranes and biofilm.
AB  - Many exciting new technologies for water-quality control combine microbiological
      processes with adsorption, advanced oxidation, a membrane or an electrode to
      improve performance, address emerging contaminants or capture renewable energy.
      An excellent example is the H2-based membrane biofilm reactor (MBfR), which
      delivers H2 gas to a biofilm that naturally accumulates on the outer surface of a
      bubbleless membrane. Autotrophic bacteria in the biofilm oxidise the H2 and use
      the electrons to reduce NO3-, CIO4- and other oxidised contaminants. This natural
      partnership of membranes and biofilm makes it possible to gain many cost,
      performance and simplicity advantages from using H2 as the electron donor for
      microbially catalysed reductions. The MBfR has been demonstrated for
      denitrification in drinking water; reduction of perchlorate in groundwater;
      reduction of selenate, chromate, trichloroethene and other emerging contaminants;
      advanced N removal in wastewater treatment and autotrophic total-N removal.

PMID- 16605036
TI  - Integration of sulphate reduction, autotrophic denitrification and nitrification
      to achieve low-cost excess sludge minimisation for Hong Kong sewage.
AB  - An integrated anaerobic-aerobic treatment system of sulphate-laden wastewater was
      proposed here to achieve low sludge production, low energy consumption and
      effective sulphide control. Before integrating the whole system, the feasibility
      of autotrophic denitrification utilising dissolved sulphide produced during
      anaerobic treatment of sulphate rich wastewater was studied here. An upflow
      anaerobic sludge blanket reactor was operated to treat sulphate-rich synthetic
      wastewater (TOC=100 mg/L and sulphate=500 mg/L) and its effluent with dissolved
      sulphide and external nitrate solution were fed into an anoxic biofilter. The
      anaerobic reactor was able to remove 77-85% of TOC at HRT of 3 h and produce 70
      90 mg S/L sulphide in dissolved form for the subsequent denitrification. The
      performance of anoxic reactor was stable, and the anoxic reactor could remove 30
      mg N/L nitrate at HRT of 2 h through autotrophic denitrification. Furthermore,
      sulphur balance for the anoxic filter showed that more than 90% of the removed
      sulphide was actually oxidised into sulphate, thereby there was no accumulation
      of sulphur particles in the filter bed. The net sludge productions were
      approximately 0.15 to 0.18 g VSS/g COD in the anaerobic reactor and 0.22 to 0.31
      g VSS/g NO3- -N in the anoxic reactor. The findings in this study will be helpful
      in developing the integrated treatment system to achieve low-cost excess sludge
      minimisation.

PMID- 16605037
TI  - Production of porous carbonaceous adsorbent from physical activation of sewage
      sludge: application to wastewater treatment.
AB  - With an objective of production of carbonaceous sorbent for industrial effluent
      treatment, physical activation by steam of biological sludge collected from the
      municipal wastewater treatment plant of Nantes (France) was studied and optimised
      using experimental design. Thus, this activation process consists of a
      carbonisation under N2 atmosphere at 600 degrees C for 1 h, followed by a thermal
      oxidation using steam (760 degrees C, 0.5 h, 2.5 L/Umin). The global mass yield
      of the process is equal to 38%. The thermal treatment allows a specific surface
      area of up to 225 m2/g to be reached, the porous structure being composed of both
      micropores and mesopores. The content of acidic surface groups is 0.71 mEq/g
      whereas that of basic surface groups is 0.55 mEq/g. The adsorption properties of
      the sorbent made from sludge are estimated with regard to various pollutants
      representative of industrial pollution of wastewaters and compared with those of
      commercial activated carbon. Whereas the adsorption capacities of organic
      micropollutants are quite low because of proportionality to the microporosity,
      the important mesoporosity of the sorbent leads to interesting properties for
      macromolecules removal from aqueous solutions, such as dyes (q(m) = 175-200
      mg/g). Furthermore, the surface functional groups and Ca2+ ions within the
      materials allow high copper ion adsorption capacities of 140 mg/g to be obtained.
      Finally, a techno-economic approach shows that the sludge activation process
      seems to be economically competitive with regard to incineration.

PMID- 16605038
TI  - High-solids centrifuge is a boon and a curse for managing anaerobically digested
      biosolids.
AB  - High-solids centrifugation can reduce the cost of managing or disposing of
      anaerobically digested biosolids. High-solids centrifuges can increase relative
      cake solids by as much as 5% DS compared with other dewatering devices, such as
      belt filter presses, with a resulting 15-20% reduction in overall mass of hauled
      biosolids. Cost reductions can be similar (15-20%) or more, depending on the type
      of disposal or management involved. For example, the additional removal of water
      from the cake increases the energy content in the biosolids, thereby facilitating
      incineration or heat drying processes. For land application, the benefits are
      more mixed. As explained in this paper, increases in biosolids odours associated
      with high-solids centrifuges may increase digestion requirements and may compel
      producers to transport biosolids to more remote, distant sites, potentially
      increasing transportation costs. High-solids centrifuges shear anaerobically
      digested biosolids. The shear results in a net increase in labile protein, an
      odour precursor. Additionally, high-solids centrifugation also results in the
      inhibition of methanogenesis, a major mechanism for degradation of organosulphur
      odours. Therefore, the risks and benefits should both be weighed when considering
      high-solids centrifuges for land application of anaerobically digested biosolids.

PMID- 16605039
TI  - Anaerobic digestion with partial ozonation minimises greenhouse gas emission from
      sludge treatment and disposal.
AB  - A novel anaerobic digestion process combined with partial ozonation on digested
      sludge was demonstrated for improving sludge digestion and biogas recovery by
      full-scale testing for 2 years and its performance was compared with a
      simultaneously operated conventional anaerobic digestion process. The novel
      process requires two essential modifications, which are ozonation for enhancing
      the biological degradability of sludge organics and concentrating of solids in
      the digester through a solid/liquid separation for extension of SRT. These
      modifications resulted in high VSS degradation efficiency of ca. 88%, as much as
      1.3 times of methane production and more than 70% reduction in dewatered sludge
      cake production. Based on the performance, its energy demands and contribution
      for minimisation of greenhouse gas emission was evaluated throughout an entire
      study of sludge treatment and disposal schemes in a municipality for 130,000 p.e.
      The analysis indicated that the novel process with power generation from biogas
      would lead to minimal greenhouse gas emission because the extra energy production
      from the scheme was expected to cover all of the energy demand for the plant
      operation, and the remarkable reduction in dewatered sludge cake volumes makes it
      possible to reduce N2O discharge and consumption of fossil fuel in the subsequent
      sludge incineration processes.

PMID- 16605040
TI  - Measurement implications when developing and implementing interventions.

PMID- 16605041
TI  - Psychometric evaluation of the Shared Care Instrument in a sample of home health
      care family dyads.
AB  - Researchers have studied negative effects of caregiving on a family caregiver;
      however, less is known about positive aspects of exchanging assistance for both
      members of a family caregiving dyad. In a previous naturalistic inquiry the
      author indentified a basis for studying caregiving interactions was a construct
      called shared care. The three components of shared care identified in the
      naturalistic inquiry were communication, decision making, and reciprocity. The
      Shared Care Instrument (SCI) was developed to measure the construct. The purpose
      of this study was to assess the psychometric properties of the SCI, and to assess
      its construct and criterion-related validity, A sample of home care family dyads
      (110 patients and 109 family members) returned usable survey questionnaires.
      Results indicated the Cronbach's alphas for the patient group for the SCI
      subscales ranged from .78 to .84, and .77 to .79 for family members. Factor
      analysis supported the underlying theoretical basis and factor structure of the
      SCI. Criterion-related validity was also supported. Therefore, the results of
      this study provide initial evidence for the reliability and validity of the SCI
      for use with family caregiving dyads. The findings support the need for
      additional testing of the SCI.

PMID- 16605042
TI  - Development and validation of the Emotional Intimacy Scale.
AB  - Although many measures have been developed to capture elements of social support,
      only a few include an assessment of emotional intimacy. Emotional intimacy
      involves a perception of closeness to another that allows sharing of personal
      feelings, accompanied by expectations of understanding, affirmation, and
      demonstrations of caring. The 5-item Emotional Intimacy Scale (EIS) was developed
      to assess the emotional intimacy component in one close relationship. A sample of
      90 women with rheumatoid arthritis was used to assess the reliability and
      validity of the scale. Internal consistency and test-retest reliability for a 6
      week period were .88 and .85, respectively. To assess construct validity,
      significant, positive correlations were obtained between the EIS and measures of
      social support, self-efficacy, perceived health competence, reappraisal coping
      behaviors, life satisfaction, and positive affect. Significant negative
      correlations were obtained between the EIS and perceived stress levels,
      helplessness, negative pain coping behaviors, pain, and fatigue. In support of
      criterion-related validity, the EIS predicted outcomes from an intervention
      program. To further assess criterion-related validity, scores on the EIS and
      helplessness predicted scores on two indicators of psychological well-being that
      measured positive affect and life satisfaction. The EIS is a brief measure of
      emotional intimacy with good psychometric properties.

PMID- 16605043
TI  - Need for population specific validation of a portable metabolic testing system: a
      case of sedentary pregnant women.
AB  - Commercially available portable metabolic systems have been validated with
      samples of young, healthy, and well-fit subjects, but use of these systems with a
      special population, such as healthy but sedentary pregnant women, requires a
      unique set of considerations. These include a woman's limited testing time
      necessary for fetal safety, relatively low oxygen consumption, and the unique
      physiology of pregnancy (woman, the placenta, and the fetus). The purpose of this
      study was to validate a portable metabolic testing system (VO2000) with healthy
      sedentary pregnant women. A total of 9 sedentary pregnant women who averaged 30
      years of age (SD=3), 93 kg (SD=19) weight, 163 cm (SD=7) height, and at 19 weeks'
      gestation (SD=5) volunteered to participate. Submaximum fitness tests using the
      Cornell protocol were conducted once with two systems (VO2000 and CPX/D, a
      reference) simultaneously, and then subsequently twice with one system (VO2000).
      The VO2000 consistently overestimated VO2 measurement, compared to the same
      manufacturer's reference system, by 4.4 +/- 3.6 (SD) ml/kg/min, and when VO2000
      was used twice, the mean difference was statistically significant (1.0 +/- 1.8
      [SD] ml/kg/min; t(45) = 3.9, p < .001). The results of the study show that
      although VO2000 is an established and validated portable metabolic system for
      measurement on adult males and females who are relatively well fit, this portable
      system consistently overestimates VO2 readings for pregnant women compared to
      standard full-size system. Measurements, when repeated, were not consistent.

PMID- 16605044
TI  - Commitment to Health Scale.
AB  - The Commitment to Health Scale (CHS) was developed to predict likelihood of
      clients being able to permanently adopt new health-promoting behaviors.
      Commitment is based on the association between starting new health behaviors and
      long-term performance of those behaviors. The CHS evolved from an examination of
      Prochaska and DiClemente's Stages of Change Algorithm, Decisional Balance Scale,
      and Strong and Weak Principle (Velicer, Rossi, Prochaska, & DiClemente, 1996).
      Scale items were assessed by classical and Rasch measurement methods. The
      research was performed in three separate studies at various locations in the
      United States and included approximately 1100 subjects. A new unidimensional
      variable was identified called Commitment to Health. Internal consistency
      reliability of the scale was .94 (Cronbach's alpha). External validity and
      reliability were assessed based on expected and observed ordering and between
      known groups. Scale scores predicted self-reported health behaviors and body mass
      index.

PMID- 16605045
TI  - Cultural factors and medication compliance in Chinese immigrants who are taking
      antihypertensive medications: instrument development.
AB  - Chinese immigrants in the United States have a moderate to high prevalence of
      hypertension, but little is known about antihypertensive medication compliance in
      Chinese immigrants. This study presents some first-generation measures of
      antihypertensive medication compliance in a sample of Chinese immigrants. A
      literature review and two qualitative pilot studies were conducted to generate
      culturally sensitive instruments. Items were developed to assess cultural factors
      and medication compliance in Chinese immigrants receiving antihypertensive
      medications. Cultural factors included measures of cultural health perception of
      hypertension, health perceptions of Chinese herbs, health perceptions of Western
      medications, beneficial self-care behaviors, and social support. Four medication
      compliance scales were developed. The applicability of these scales was tested in
      a Chinese immigrant population (n=200). Cronbach's alpha for the cultural factors
      scales ranged from .57 to .91. Two of the medication compliance scales had
      Cronbach's alphas above .60. Results showed that most of the scales are
      applicable and acceptable in a Chinese immigrant population and had good
      reliability. However, further testing with a larger sample in other regions of
      the country is indicated.

PMID- 16605046
TI  - Local therapy, systemic benefit: challenging the paradigm of biological
      predeterminism.
AB  - This paper briefly reviews the historical evolution of paradigms that have been
      purported to characterise the clinical behaviour of breast cancer, with the
      intention of guiding treatment approaches. Results from randomised clinical
      trials and the explosion of knowledge in the area of cancer biology have
      discredited the monolithic paradigms that had dominated thinking about breast
      cancer in the past. Contemporary notions of breast cancer biology recognise that,
      although some cancers disseminate well before becoming clinically detectable,
      acquisition of a metastatic phenotype can occur at any point (or not at all) in
      the local evolution of the tumour. As a consequence, both systemic and timely
      local--regional therapies can be expected to influence disease dissemination and
      patient survival. This is consistent with results observed in clinical trials,
      overviews of which indicate that prevention of four local recurrences will, on
      the average, prevent one death from breast cancer. Optimisation of local-regional
      treatment is an important goal in breast cancer management.

PMID- 16605047
TI  - Radiobiology of breast cancer.
AB  - Advances in molecular and cellular biology are transforming our understanding of
      breast cancer and promise the same for radiotherapy over the next few years. At
      the clinical level, the molecular basis of fractionation dependency and other
      tumour and normal tissue responses are likely to become clearer. More
      importantly, they will become useful in the clinic, where molecular
      characterisation of the patient and tumour will start to determine therapeutic
      options. Although many of the fundamental processes are only amenable to study in
      laboratory systems, the power of array-based technologies makes it possibly to
      address highly relevant questions in the clinic, using functional imaging and/or
      tissue biopsies. To help clinical oncologists exploit these opportunities in
      translational research, some aspects of the molecular and cellular basis of
      radiotherapy are described below in their relation to breast cancer.

PMID- 16605048
TI  - Radiotherapy for ductal carcinoma in situ.
AB  - AIMS: The introduction of breast screening mammography has led to an increase in
      the diagnosis of ductal carcinoma in situ (DCIS). Mastectomy gives high rates of
      local control. However, most cases are suitable for local excision. The aim of
      this article is to review the role of radiotherapy in the treatment of DCIS after
      breast conserving surgery. MATERIAL AND METHODS: A review of the literature
      relating to radiotherapy and DCIS RESULTS: The published trials show that
      adjuvant radiotherapy after breast conserving surgery halves the ipsilateral
      recurrence rates of DCIS and invasive cancer. No subgroups have been reliably
      identified that do not benefit from adjuvant radiotherapy. Risk factors for
      recurrence are discussed. DISCUSSION: All patients with DCIS have potential
      benefit to gain from adjuvant radiotherapy. However, radiotherapy also has
      adverse effects and represents over-treatment from many women. Support should be
      given to current trials which are assessing endocrine treatment of DCIS, and
      whether radiotherapy can reasonably be omitted in lower risk disease.

PMID- 16605049
TI  - Postmastectomy radiotherapy.
AB  - Radiotherapy given after mastectomy (PMRT) will reduce the risk of local
      recurrence by about two-thirds. The absolute benefit will depend on the risk of
      local recurrence, which will depend on pathological characteristics (tumour size,
      nodal status, etc.) but also the type and extent of the surgery. The overall
      effect of radiotherapy on survival has changed with time. Improved local control
      reduces the risk of dying from breast caner, presumably by preventing secondary
      dissemination from recurrent disease. Older radiotherapy techniques were
      associated with an excess risk of cardiovascular death, which counterbalanced the
      improvement in survival seen with better local control. More recent studies show
      that modern radiotherapy techniques can improve local control and avoid cardiac
      morbidity. PMRT remains an important component of the management of patients with
      breast cancer.

PMID- 16605050
TI  - When may adjuvant radiotherapy be avoided in operable breast cancer?
AB  - Randomised trials in which the omission of radiotherapy has been tested after
      breast-conserving surgery, with or without adjuvant systemic therapy, show a
      significant four- to five-fold reduction in local recurrence. As yet, no subgroup
      of women managed by breast-conserving surgery has been identified from whom
      radiotherapy can be withheld. Few randomised data have been published on the
      effect of omission of radiotherapy on local control, quality of life and costs,
      particularly in older women for whom the risk of local recurrence is generally
      lower. Ongoing trials are evaluating the role of radiotherapy in this population
      of low risk, older women. Adjuvant radiotherapy after breast-conserving surgery
      or mastectomy significantly reduces the incidence of local recurrence. In women
      who have had a mastectomy at high risk of recurrence (> 20% risk of recurrence at
      10 years), adjuvant radiotherapy improves survival if combined with adjuvant
      systemic therapy. Among women with T3 tumours, and those with four or more
      involved axillary nodes treated by mastectomy, postoperative radiotherapy is the
      standard of care. For women at intermediate risk of recurrence (i.e. <15% 10-year
      risk of recurrence after surgery and systemic therapy alone), with one to three
      involved nodes or node negative with other risk factors, the role of radiotherapy
      is unclear. Clinical trials to assess the role of postmastectomy radiotherapy
      (PMRT) in this setting are needed. For pT1-2, pNO tumours without other risk
      factors, there is no evidence at present that PMRT is needed.

PMID- 16605051
TI  - Treatment planning challenges in breast irradiation: the ideal and the practical.
AB  - Radiotherapy has recently undergone some interesting developments, with the
      introduction of new technology and techniques in many departments. Arguably, with
      this comes an increase in the expectation of its capability. The treatment site
      that continues to represent most of the workload in our departments is breast. We
      should consider how relevant these contemporary changes are in the treatment of
      breast cancer. In this paper, we review some of the challenges in planning breast
      treatments and how they may be addressed with contemporary radiotherapy
      techniques.

PMID- 16605052
TI  - Placing the boost in breast-conservation radiotherapy: A review of the role,
      indications and techniques for breast-boost radiotherapy.
AB  - Randomised trials have established that the addition of a boost dose of
      radiotherapy to the lumpectomy site after whole-breast adjuvant radiotherapy
      further improves local control achieved by whole-breast radiotherapy alone. The
      absolute size of this benefit varies according to the baseline risk of local
      recurrence. Age is the strongest predictor of benefit. Below the age of 40 years,
      the absolute benefit of a boost seems to be substantial, and there are no clearly
      identified groups unlikely to benefit. Above the age of 50 years, the benefit is
      small, and several additional risk factors for local failure would need to be
      present to merit boost treatment. These may include tumour size, high grade, high
      mitotic rate, lymphovascular invasion, extensive and high grade associated with
      intraduct carcinoma, receptor-positive tumours when avoidance of anti-oestrogen
      therapy is desired or receptor-negative tumours. Other independent reasonable
      indications for the use of a boost would be positive margins where further
      surgery is not indicated. If a boost is indicated, a variety of techniques may be
      used and toxicity and cosmetic results remain highly acceptable. Overall, there
      seems to be no substantial differences in boost technique results; however,
      interstitial techniques may have advantages for deeper targets compared with
      electrons. Irrespective of technique, accurate localisation will maximise the
      benefit of a boost. Surgical clips are strongly recommended to facilitate
      localisation.

PMID- 16605053
TI  - Breast-conserving surgery with intra-operative radiotherapy: the right approach
      for the 21st century?
AB  - Wide local excision followed by external beam radiation therapy (EBRT) to the
      whole breast has become the standard of care for most patients with localised
      'early' breast cancer in the UK, Europe, and the USA. Local relapse rates are
      low, and overall survival figures have improved during the past decade, with the
      advent of more effective systemic endocrine- and chemo-therapy. A policy of EBRT
      for every patient undergoing breast conserving surgery (BCS) is however
      associated with a number of practical difficulties, acute radiation side effects
      and longer term toxicity, all of which detract from the obvious benefits of EBRT.
      In addition, with a disease as common as early breast cancer and a treatment
      programme typically requiring sophisticated radiation planning and many fractions
      of treatment, the policy of BCS plus EBRT has enormous resource implications
      within departments of oncology, greatly contributing to lengthy pre-treatment
      delays. For all these reasons, we and others have developed an increasing
      interest in techniques of partial breast irradiation, with an emphasis in our own
      Department on the emerging technique of intra-operative radiotherapy (IORT),
      which we initially employed as a boost to the tumour bed for use in conjunction
      with EBRT to the whole breast. To test the possibility of replacing the whole of
      the EBRT 3-6 week programme by a single application of IORT at the time of
      surgery, we and others have commenced a large scale prospectively randomised
      clinical trail in selected patients. Nine international centres are currently
      participating, and 350 patients have now been randomised to receive either IORT
      as part of the initial surgical excision or conventional EBRT with a pragmatic
      dose policy according to the preference of the contributing centre. The majority
      of patients undergoing IORT receive this at the time of initial surgery but it is
      also permissible within the trial programme to randomise suitable patients after
      the excised specimen has been histologically examined, thus avoiding any
      unsuitable patients - for example, those with a lobular carcinoma. These patients
      will be stratified and assessed separately from the 'pre-pathology' group, whose
      surgery and IORT is completed within a single session; if the latter patients are
      found to have unfavourable histology we have the facility, within the trial, to
      add EBRT. The trial is ongoing and our early experience has been encouraging. We
      have also recently assessed the long term local failure rate in patients offered
      IORT as a tumour bed boost, in conjunction with conventional EBRT. This
      methodology will also be the subject of a future randomised clinical trial.

PMID- 16605054
TI  - Complications of breast-cancer radiotherapy.
AB  - Although the beneficial effect of postoperative radiotherapy for breast cancer is
      well documented, this treatment may be related to a number of complications,
      which may affect patient quality of life and possibly survival. Among significant
      long-term irradiation sequelae are cardiac and lung damage, lymphoedema, brachial
      plexopathy, impaired shoulder mobility and second malignancies. The risk of these
      complications, particularly high with old, suboptimal irradiation techniques, has
      decreased with the introduction of modern technologies. In this paper, we review
      the contemporary knowledge on the toxicity of breast-cancer radiotherapy and
      discuss possible preventive measures.

PMID- 16605055
TI  - Cardiac risks of breast-cancer radiotherapy: a contemporary view.
AB  - For some time, there has been compelling evidence both from randomised-controlled
      trials and from observational studies, that some of the breast-cancer
      radiotherapy regimens used in the past have led to increased risk of mortality
      from heart disease. There is also some evidence that the more recent regimens
      used in the USA are associated with lower risks than previous ones, but it is not
      clear whether current regimens are free from cardiac risk, especially in the
      light of recent evidence from the survivors of the bombings of Hiroshima and
      Nagasaki, in whom a clear relationship was observed between the risk of mortality
      from heart disease and radiation dose for doses in the range 0-4 Gy. Mortality
      from radiation-induced heart disease usually occurs at least a decade after
      irradiation. Symptomatic heart disease might have a much shorter induction
      period, but little information about it is available at present. Subclinical
      vascular abnormalities have been observed within months of irradiation, via
      myocardial perfusion imaging studies, but little is known about the relationship
      between these and later overt heart disease. At present, few data relate heart
      dose and other specific characteristics of breast radiotherapy to cardiac
      outcome. Further information on these topics is needed to enable estimation of
      the cardiac risk, that is likely to arise from radiotherapy regimens in current
      use and from those being considered for future use. Such knowledge would
      facilitate radiotherapy treatment planning and enable a reduction in cardiac risk
      while maintaining the known benefit in terms of breast cancer mortality.

PMID- 16605056
TI  - Delaying radiotherapy for the delivery of adjuvant chemotherapy in the combined
      modality treatment of early breast cancer: is it disadvantageous and could
      combined treatment be the answer?
AB  - Women with early stage breast cancer are increasingly being treated with both
      adjuvant chemotherapy and radiotherapy. The optimal sequence of these two
      treatment modalities is yet to be defined. It remains controversial whether
      delaying radiotherapy in order to deliver chemotherapy compromises local disease
      control and survival. Consequently, clinical practice in the UK is divided, with
      a number of different combination schedules being used in an effort to bring
      forward the start of radiotherapy. In practice, however, any benefit in local
      control must be balanced against a potential increase in toxicity. A review of
      the current literature on the effect of radiotherapy delay is presented, together
      with data on the toxicity of combined chemo-radiotherapy schedules and recent
      data from clinical trials designed to determine the optimal sequencing of
      chemotherapy and radiotherapy.

PMID- 16605057
TI  - Radiotherapy and genetic predisposition to breast cancer.
AB  - Cancer genetics is becoming increasingly integrated into oncological care;
      particularly in breast cancer management. The recognition of monogenic breast
      cancer predisposition syndromes, such as BRCA, is critical as there is also a
      risk of other cancers in addition to a markedly elevated risk of contralateral
      breast cancer. In individuals with breast cancer due to some predisposition
      genes, radiation should be avoided, e.g. the ATM and TP53 genes, but there is
      still controversy as to whether radiation should be used in BRCA1/2 mutation
      carriers and more follow-up is needed. There are some radiation-sensitive genetic
      conditions where, if breast cancer occurs (as it may occur in any individual, not
      necessarily due to an increased risk associated with the condition), radiation
      should be avoided. These conditions are often associated with dysmorphic
      features. If such features are noticed then the advice of a geneticist should be
      sought urgently prior to giving radiation.

PMID- 16605058
TI  - Moving to a high-tech approach to the irradiation of early breast cancer: is it
      possible to balance efficacy, morbidity and resource use?
AB  - There is substantial evidence documenting the potential morbidity associated with
      radiotherapy in early breast cancer. An appraisal of current standard radiation
      practice is therefore necessary, given that women are surviving longer, have an
      improved quality of life, and are overcoming subsequent side-effects caused by
      postoperative irradiation. New technology allows the application of more complex
      approaches. This discussion paper considers some of the benefits of the
      widespread use of new complex approaches, such as intensity-modulated
      radiotherapy (IMRT) in the light of staffing and equipment shortfalls, and
      possible consequences on waiting times for treatment. The discussion is
      considered under the following themes: (1) which women with breast cancer benefit
      from complex treatment approaches? (2) What is the role of treatment accuracy in
      limiting morbidity? And (3) what is the potential effect of complex breast
      irradiation approaches on service delivery? In the UK, and globally, many
      departments are struggling to meet waiting-time guidelines. The use of more
      complex approaches for breast irradiation may increase this difficulty. However,
      a number of simple technical changes can be used to enhance efficacy and reduce
      levels of normal tissue morbidity. A sub-set of women who are at greatest risk
      from normal tissue morbidity or reduced cosmesis should be accurately defined in
      order to allow departments to plan their treatment strategies with optimal use of
      resources.

PMID- 16605059
TI  - [Nurses in private practice in France].
AB  - In the French health care system, most nurses work in hospitals as salaried, but
      a number are also salaried in health centers or operate in their private offices.
      About 48,000 are private practitioners, they provide nearly all the ambulatory
      nursing care to the population. A survey undertaken in early 2004 shows that on
      the average, their weekly working time is 40 hours: 10 hours are devoted to
      injections, 9 to dressings, 17 to nursing care and 4 to other activities. Out of
      10 nurses in private practice, 3 think that their workload is too heavy.
      Moreover, 19% declare that they are willing to leave private practice over the 3
      coming years. If all the individual plans become reality, more that 9000 private
      nurses would disappear during the coming years from a workforce of 48,000:2900
      would retire, 2700 would become salaried in hospitals, 3200 would take up an
      other job and 400 would become temporary workers in interim companies. Will the
      tasks they let be carried out by their remaining colleagues? No doubt that this
      will not be the case only 7% of the surveyed professionals declare that they are
      willing to increase their workload. As nurses shortage in French hospitals is
      evident nowadays, it seems that shortage in ambulatory care is unavoidable. The
      surveyed nurses point out 3 important difficulties they are encountering. One
      nurse out of 4 complain about the heavy administrative procedures i.e. the
      numerous and complex forms they have to fill out. One out of 6 complains about
      the lack of locum tenets. Furthermore, one out of 15 are in favour of suppressing
      the official "Nursing Care Approach" which was promoted recently, precisely to
      highlight the importance of their professional work.

PMID- 16605060
TI  - [Physiotherapists in private practice in France].
AB  - In France, most of the physiotherapists providing ambulatory care are in private
      practice: they are paid on a fee-for-service basis by the patients who are
      reimbursed by the Sickness Insurance Fund. A survey on a sample of 2000 (out of
      40,000) private practitioners was undertaken in early 2004. As concerns their
      workload, only 4% think that it is "not sufficient" whereas 66% estimate it
      "certainly sufficient". Such a feature is noteworthy, as private practitioners
      are most often fearful of lack of work. In the coming years, one physiotherapist
      out of 10 envisages to increase his workload, whereas 27% are in favour of a
      reduction. Furthermore, the survey shows that more than one third of private
      physiotherapists plan to offer to patients services which are not listed in the
      contractual agreement document signed by their profession and the Sickness
      Insurance Fund. The trend is most noticeable among the young practitioners. As
      the feeling of medical doctors shortage is currently widespread in France, the
      public debates are focused on the issue of task delegation. After the survey, 54%
      private physiotherapists are in favour of task delegation, 24% have an opposite
      opinion and 22% do not express a clear-cut position. However, an in-depth
      analysis of the written answers to the question shows that a large majority do
      not accept to replace medical doctors for performing the tasks which are of a
      subordinate level, are not significant or are time-consuming (e.g. filling out
      the administrative forms). The question of vocabulary is fundamental in the
      matter. Moreover, a process of task delegation implies that certain tasks carried
      out by an overburdened profession are transferred to an other profession less
      heavily surcharged. Is it the case of French private physiotherapists whose two
      thirds declare that "their workload is certainly sufficient"?

PMID- 16605061
TI  - First report of Litomosa spp. (Nematoda: Filarioidea) from Malagasy bats; review
      of the genus and relationships between species.
AB  - The presence of the filarial genus Litomosa in Malagasy bats is demonstrated by
      the finding of L. goodmani n. sp. from Miniopterus gleni and Litomosa sp. (male
      unknown) from M. manavi, both in the Special Reserve of Ankarana. These materials
      are compared to the 22 Litomosa species, including two Indian species originally
      placed in the genus Litomosoides, L. fotedari (Gupta and Trivedi, 1989) n. comb.
      and L. tewarii (Gupta and Trivedi, 1989) n. comb., and the new taxon L. seurati
      n. sp. (= L. beaucournui Bain, 1966 pro parte), type-host Rhinolophus ferrum
      equinum, Algeria, distinguished by the narrow area rugosa and the female caudal
      extremity with two conspicuous points, instead of several small ones. The
      Malagasy material belongs to a group of species close to the type, L. filaria,
      which have a male area rugosa composed of cuticular bosses and microfilariae
      folded within the sheath, and which are parasitic in Vespertilionidae,
      Hipposideridae and Rhinolophidae from Africa and Europe. The two Malagasy species
      resemble L. seurati n. sp., L. beshkovi Jancev, 1971, L. chiropterum Ortlepp,
      1932, L. adami Petit, 1980 and L. ottavianii Lagrange et Bettini, 1948, with the
      enlarged third segment of the buccal capsule. L. goodmani n. sp. is distinct with
      its small size and female caudal extremity with a single point, which is
      suppressed in old mature worms; the females of Litomosa sp. have two conical
      points. Relationships among Litomosa species appear to be dependent upon both the
      chiropteran host groups and the geographical region.

PMID- 16605062
TI  - [Phlebotomine sandflies (Diptera: Psychodidae) of French Guiana. I--Description
      of the male of Lutzomyia (Trichopygomyia) depaquiti n. sp].
AB  - Description of a new tropical species of French Guiana: Lutzomyia
      (Trichopygomyia) depaquiti. The principal character is the aedeagus morphology
      that presents lateral expansions like a marine anchor. An other particularity is
      centered on the complex paramere with a lateral lobe. Holotype is deposited at
      the National Museum of Natural History of Paris.

PMID- 16605063
TI  - Isolation of Leishmania (Viannia) braziliensis from Lutzomyia spinicrassa
      (species group Verrucarum) Morales Osorno Mesa, Osorno and Hoyos 1969, in the
      Venezuelan Andean region.
AB  - Natural infection with Leishmania spp. in phlebotomine sandflies was searched for
      during a longitudinal study carried out from July 1997 to July 1998 in the
      village Catarnica, Municipality Independencia, Tachira State. This hamlet is an
      old endemic focus of cutaneous leishmaniasis in the Venezuelan Andean region,
      which lies close to the Colombian border at 1,300 m a.s.l., in an agricultural
      area mainly used for cultivating coffee. Phlebotomine sandflies were collected
      using Shannon traps placed in the peridomestic habitat from 19:00 to 21:00 hs.
      Males were stored in alcohol 70 % while females were kept in Nunc vials with 10 %
      DMSO and cryopreserved in liquid nitrogen for subsequent dissection and
      identification. The most abundant anthropophilic species was Lutzomyia
      spinicrassa with 3,032 males and 4,290 females (85.4%). Among 1,633 (38%) females
      of Lu. spinicrassa dissected, 26 11.6%) were infected with promastigotes, while
      no natural infection was found in 209 females of other species. The flagellates
      were identified as Leishmania braziliensis braziliensis using PCR with species
      specific primers derived from nuclear DNA and hybridization using species
      specific probe labelled with digoxigenin. This parasite had been previously
      isolated from patients with cutaneous leishmaniasis from the same area. These
      results show Lu. spinicrassa as a new proven vector of Leishmania braziliensis in
      the Andean region of Venezuela.

PMID- 16605064
TI  - Phlebotominae (Diptera: Psychodidae) of human leishmaniosis sites in Tunisia.
AB  - In order to identify the phlebotomine sandfly populations in Tunisian
      leishmaniosis foci, an entomological survey was carried out through three
      entomological seasons (2002-2003-2004) in 19 visceral and cutaneous leishmaniosis
      areas, located in six bioclimatic zones. Sandfly collections were based on light
      and sticky traps placed around human leishmaniosis cases. 8,722 phlebotomine
      sandflies belonging to 12 species were collected. The dominance of subgenus
      Larroussius species in northern foci, Phlebotomus papatasi in south-western foci
      and their co-dominance in the centre of the country is in accordance with the
      distribution of Leishmania infantum and L. major in Tunisia. The low density
      found in the historical zoonotic cutaneous leishmaniosis focus of Metlaoui in the
      south-west may indicate the high competence of the local populations. Studied
      phlebotomine settlements have showed a low specific diversity in most of the
      studied sites. In L. infantum areas, the dominant species were respectively: P.
      perfiliewi in the cutaneous leishmaniosis site of the humid bioclimatic stage, P.
      perniciosus in the cutaneous and visceral leishmaniosis foci of semi-arid and
      arid bioclimatic stages and P. longicuspis in the visceral leishmaniosis focus of
      saharan bioclimate. In the zoonotic cutaneous leishmaniosis foci, P. papatasi was
      a dominant species. In the well-known south-eastern foci of cutaneous
      leishmaniosis due to L. killicki, P. sergenti was a dominant species with P.
      perniciosus. In the central emerging foci of L. killicki, P. perniciosus was a
      dominant species in some sites whereas it was very rare in others. In these
      sites, the subgenus Paraphlebotomus was always present with a higher abundance of
      P. alexandri than P. sergenti.

PMID- 16605065
TI  - [African Program for Onchocerciasis Control (APOC): Onchocerca volvulus
      transmission by Simulium damnosum s. l. in two regions of the Central African
      Republic].
AB  - Entomological baseline data were collected in the villages of Zinga and Boali
      Falls in Central African Republic (CAR) in view of the long term impact
      assessment of community-directed treatment with ivermectin (CDTI). Morphological
      determinations revealed that flies caught in both sites belong to the sub-group
      Sou/Sq. In Boali, the nuisance was relatively high with biting rates averaging
      243 bites/man/day, with a parous rate of 61.6% and a crude annual transmission
      potential (ATP) of 8,259 infective larvae/man/year; and the average number of
      infective larvae per 1,000 parous flies was 177. In Zinga, the mean biting rate
      was 191 bites/man/day, with a parous rate of 51.6%, a crude ATP of 3,422, and 86
      infective larvae per 1,000 porous flies. In conclusion, the vectorial capacity
      and the entomological indices recorded are characteristic of high onchocerciasis
      transmission zones. However, some of the infective larvae found, maybe of animal
      origin, need identification to better determine the real level of endemicity.

PMID- 16605066
TI  - [Lamellodiscus sanfilippoi n. sp. (Monogenea, Diplectanidae) parasite from the
      gills of Diplodus sargus (Teleostei, Sparidae) in Mediterranean Sea].
AB  - Lamellodiscus sanfilippoi n. sp. takes place, among the other species of
      Lamellodiscus, in the "ergensi" sub-group (Amine et Euzet, 2005) characterized by
      the morphology of the dorsal lateral bars of the haptor. This sub-group
      comprises, in the Mediterranean, L. ergensi Euzet and Oliver, 1966, L. kechemirae
      Amine and Euzet, 2005, L. tomentosus Amine and Euzet, 2005, all parasite of
      Diplodus sargus, and L. baeri Oliver, 1974 parasite of Pagrus pagrus. L.
      sanfilippoi can be distinguished from the previous species by the morphology and
      size of the dorsal lateral bars. The new species is close to Lamellodiscus
      furcillatus Kritsky, Jimenez-Ruiz and Sey, 2000, a parasite of Diplodus noct in
      the Persian Gulf, but differs by the size of the haptoral sclerotised pieces and
      the morphology of the male copulatory apparatus. Lamellodiscus gussevi Sanfilippo
      (1978) et Lamellodiscus abbreviatus Sanfilippo (1978) are considered as nomina
      nuda.

PMID- 16605067
TI  - Growth-promoting effect on iron-sulfur proteins on axenic cultures of Entamoeba
      dispar.
AB  - A growth-promoting factor (GPF) that promotes the growth of Entamoeba dispar
      under axenic culture conditions was found in fractions of mitochondria (Mt),
      hydrogenosomes (Hg) and chloroplasts (Cp) obtained from cells of six different
      protozoan, mammalian and plant species. We were able to extract the GPF from the
      Cp-rich leaf cells of a plant (spiderwort: Commelina communis L.) in an acetone
      soluble fraction as a complex of chlorophyll with low molecular weight proteins
      (molecular weight [MW] approximately 4,600). We also found that on treatment with
      0.6% complexes of 2-mercapthoethanol (2ME), complexes of chlorophyll-a with iron
      sulphur (Fe-S) proteins (e.g., ferredoxins [Fd] from spinach and Clostridium
      pasteurianum) and noncomplex rubredoxin (Rd) from C. posteurianum have a growth
      promoting effect on E. dispar. These findings suggest that E. dispar may lack a
      sufficient quantity of some essential components of Fe-S proteins, such as Fe-S
      center.

PMID- 16605068
TI  - Serratospiculosis in falcons from Kuwait: incidence, pathogenicity and treatment
      with melarsomine and ivermectin.
AB  - The aims of this study were to determine the incidence of the filarial avian
      nematode Serratospiculum seurati in falcons from Kuwait, report clinical signs
      and find an effective therapy. Naturally occurring S. seurati infestation was
      diagnosed in 149 (8.7%) out of 1,706 captive falcons examined between May 2003
      and April 2005, and 140 of these were treated with melarsomine at dosage of 0.25
      mg/kg injected intramuscularly for two days, and ivermectin, injected once at the
      dose of 1 mg/kg, 10 days later. Infestation was reportedly symptomatic in 107
      (71.8%) and non-symptomatic in 42 (28.2%) falcons. Signs reported more often were
      dyspnoea (58.8%), reduced speed and strength in flight (56%), weight loss
      (38.3%), anorexia/poor appetite (22.4%) and lethargy (16.8%). After
      administration of melarsomine, signs disappeared within 1-10 days in symptomatic
      birds and improvement of flight performances was noted in non-symptomatic birds.
      Dead adult parasites were ejected in 22 cases. Embryonated eggs were not detected
      in coproscopic checks made 10 and 40 days after the end of therapy, in
      association with lasting clinical remission. The main conclusion is that
      Serratospiculum seurati is overall pathogenic for birds of prey in the Middle
      East and that melarsomine + ivermectin can be an effective protocol of therapy
      eliminating both clinical signs and parasites.

PMID- 16605069
TI  - Clinical and laboratory aspects of a trichinellosis outbreak in Izmir, Turkey.
AB  - Epidemiological, clinical and laboratory data were collected during an outbreak
      of trichinellosis, which occurred in Izmir, Turkey, between January and March
      2004. The source of the infection was raw meatballs made with a mixture of
      uncooked beef and pork. Of 474 persons who were admitted at the Ataturk Training
      and Research Hospital during this period with a history of raw meatball
      consumption, the diagnosis of trichinellosis was confirmed for 154 (32.5%, 87
      males and 67 females; mean age 31 years, range 6-67 years). Among persons with a
      confirmed diagnosis, 79% had myalgia, 77% weakness and malaise, 63% arthralgia,
      40% jaw pain, 68% fever, 63% periorbital and/or facial oedema, 49% oedema at the
      trunk and limb, 42% abdominal pain, 40% nausea and vomiting, 28% diarrhoea, 23%
      subconjunctival haemorrhage, 25% macular or petechial rash, 4% subungual
      haemorrhage, 15% cardiac complaints and 0.2% neurological complaints. Nine
      patients (5.8%) were hospitalised due to severe myalgia (n = 2), high fever (n =
      3), neurological manifestations (n = 1), thrombophlebitis (n = 2) and palmar
      erythema (n = 1). Eosinophilia was present in 88% of the confirmed cases at the
      admission. Elevated levels of serum creatine phosphokinase, lactic dehydrogenase
      and aspartate aminotransferase were detected in 72%, 70% and 16% of the confirmed
      cases, respectively. The seroconversion occurred in most of the infected people
      between the 4th and 6th weeks after the infection. All of the confirmed cases
      were treated with mebendazole. People with severe symptoms were treated also with
      prednisolone (60 mg/day for three days) and those with a moderately severe
      clinical pattern received a non-steroid anti-inflammatory drug (naproxen sodium,
      550 mg/day). All confirmed cases recovered without any clinical sequela.

PMID- 16605071
TI  - The chromosomes of Rodentolepis nana (Siebold, 1852) Spasskii, 1954 obtained from
      naturally infected mice conventionally maintained in a Braziuan laboratory animal
      house.
AB  - The karyotype of Rodentolepis nana obtained from mice in Rio de Janeiro, Brazil,
      was described. The diploid chromosome number obtained by the division of
      embryonic cells was 2n = 12. The first and the third pairs presented subterminal
      centromeres and the other pairs were all acrocentric. The studied species
      differed in chromosome morphology when compared to previous description by
      Mutafova and Gergova (1994) in Bulgaria, suggesting an intraspecific variation.

PMID- 16605070
TI  - Comparative evaluation of antibody positive titer by ELISA and IFA in Theileria
      annulata vaccinated cattle in Iran.
AB  - An enzyme linked immunosorbent assay (ELISA) was used to evaluate antibody
      positive titer in vaccinated and non-vaccinated cattle using schizont infected
      myeloid cells as an antigen. The result was compared with indirect fluorescent
      antibody level in the same animals. For this study 116 milking cows, 95
      vaccinated and 21 non-vaccinated, were bleeded in order to prepare sera. They
      were tested with both ELISA and IFA tests. 94 sera had positive antibody titer
      and 22 sera were negative through ELISA test but, with IFA test, only 89 sera
      showed positive antibody titer and 27 were negative. Thereby, it was concluded
      that the sensitivity and specificity of ELISA test in comparison with IFA test
      was 95.5% and 66.6% respectively. This study generally indicated that ELISA could
      be an effective test for sero-epidemiological investigations of bovine tropical
      theileriosis, and it is considered to be valid as an additional test to
      distinguish the vaccinated from the non vaccinated cattle in order to schedule
      vaccination programs.

PMID- 16605072
TI  - Low malaria morbidity in a cohort of Senegalese children with free access to
      health structures.
AB  - We report the impact of the free access to health facilities on malaria morbidity
      in children from two to 15 years old, during a malaria transmission season in
      Niakhar, Senegal. Between July and December 2002, 227 malaria attacks occured in
      566 children. Only one case of severe malaria was observed and no death has been
      reported. Our results demonstrate furthermore that easier access to health
      facilities and to early treatment is playing a key role in malaria control.

PMID- 16605073
TI  - The tick Ixodes granulatus infests Rattus rattus populating a small island
      offshore of Singapore.
AB  - The ixodid tick Ixodes granulosus Supino 1897 was found infesting Rattus rattus
      in Semakau island, one of the small offshore islands fringing Singapore to the
      south. None of the examined R. rattus from the other islands fringing Singapore,
      or from Singapore island were found infested. Ixodes granulatus occurs, however,
      on Singapore island on Rattus annandalei, resident of undisturbed forested
      habitats. We speculate that invading black rats in Semakau replaced autochthonous
      sylvatic rodent population and contracted their associate tick population.

PMID- 16605074
TI  - Presence of Tunga trimamillata (Insecta, Siphonaptera) in Peru.

PMID- 16605075
TI  - First report of Leishmania (L) killicki Rioux, Lanotte & Pratlong, 1986 in Libya.

PMID- 16605076
TI  - Comparison of ethylammonium formate to methanol as a mobile-phase modifier for
      reversed-phase liquid chromatography.
AB  - Ethylammonium formate (EAF), (C2H5NH3+HCO2-), is a room-temperature ionic liquid
      that has a polarity similar to that of methanol (MeOH) or acetonitrile. The
      separation at 1 mL/min of a test mixture of vitamins or phenols on a polystyrene
      divinylbenzene column using either an EAF- or MeOH-water mobile phase is similar
      in terms of both resolution and analysis time. Because the viscosity of EAF is
      higher than that of MeOH, the plate count for phenol at room temperature is lower
      by about a factor of 1.1-1.4 depending on the flow rate. However, van Deemter
      plots show that this loss in plate count at 1 mL/min can be recovered and
      improved from 1500 to 2400 plates by working at a slightly elevated temperature
      of 55 degrees C. A slower flow rate such as 0.8 mL/min can also substantially
      improve the plate count as compared to 1-1.5 mL/min. Log P (octanol partition
      coefficient) versus log k' data for a variety of neutral test solutes are again
      similar whether EAF or MeOH is used as the organic modifier. Resolution of
      certain peak pairs such as 2,4-dinitrophenol/2,4,6-trinitrophenol and p
      aminobenzoate/benzoate is enhanced using EAF as compared to MeOH. One advantage
      of EAF is that control of retention of solutes such as water-soluble vitamins
      under totally aqueous mobile phase conditions is environmentally preferable for
      quality control applications. In addition, EAF seems to be a milder mobile-phase
      modifier than MeOH for certain proteins such as lysozyme.

PMID- 16605077
TI  - Analysis of kanamycin A in human plasma and in oral dosage form by derivatization
      with 1-naphthyl isothiocyanate and high-performance liquid chromatography.
AB  - A simple and sensitive HPLC method has been developed for trace determination of
      kanamycin A by derivatization. Plasma proteins are precipitated by acetonitrile
      and chemical derivatization is performed on the supernatant containing kanamycin
      A with 1-naphthyl isothiocyanate in pyridine at 70 degrees C. After the
      derivatization reaction, a methylamine/acetonitrile solution was added to the
      reaction mixture to eliminate the excess of derivatizing agent and shorten the
      analysis time. The resulting derivative was separated using a Lichrocart
      Purospher STAR RP-18e column and water/methanol (33:67, v/v) as a mobile phase
      (detection at 230 nm). Optimization conditions for the derivatization of
      kanamycin A were investigated by HPLC. The linear range for the quantitation of
      kanamycin A in spiked plasma was over 1.2-40 microg/mL; the detection limit
      (signal to noise ratio = 3; injection volume, 10 microL) was about 0.3 microg/mL.
      The relative standard deviation was less than 2.9% for intra-day assay (n = 6)
      and inter-day assay (n = 6) and relative recoveries were found to be greater than
      98%. Preliminary application of the method for monitoring kanamycin A in humans
      upon intramuscular injection of the injection product demonstrated the usefulness
      of the assay for clinical studies. The proposed method can also be used to
      analyze the compound in pharmaceutical formulations.

PMID- 16605078
TI  - Microwave- and ultrasound-assisted extraction of vanillin and its quantification
      by high-performance liquid chromatography in Vanilla planifolia.
AB  - Microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE) and
      conventional extraction of vanillin and its quantification by HPLC in pods of
      Vanilla planifolia is described. A range of nonpolar to polar solvents were used
      for the extraction of vanillin employing MAE, UAE and conventional methods.
      Various extraction parameters such as nature of the solvent, solvent volume, time
      of irradiation, microwave and ultrasound energy inputs were optimized. HPLC was
      performed on RP ODS column (4.6 mm ID x 250 mm, 5 microm, Waters), a photodiode
      array detector (Waters 2996) using gradient solvent system of ACN and ortho
      phosphoric acid in water (0.001:99.999 v/v) at 25 degrees C. Regression equation
      revealed a linear relationship (r2 > 0.9998) between the mass of vanillin
      injected and the peak areas. The detection limit (S/N = 3) and limit of
      quantification (S/N = 10) were 0.65 and 1.2 microg/g, respectively. Recovery was
      achieved in the range 98.5-99.6% for vanillin. Maximum yield of vanilla extract
      (29.81, 29.068 and 14.31% by conventional extraction, MAE and UAE, respectively)
      was found in a mixture of ethanol/water (40:60 v/v). Dehydrated ethanolic extract
      showed the highest amount of vanillin (1.8, 1.25 and 0.99% by MAE, conventional
      extraction and UAE, respectively).

PMID- 16605079
TI  - Simple and sensitive high-performance liquid chromatography method for the
      quantitation of indinavir in rat plasma and central nervous system.
AB  - A simple and sensitive RP-HPLC method using UV detection (215 nm) was developed
      for the determination of indinavir concentrations in rat plasma, cerebrospinal
      fluid (CSF), and brain tissue homogenates. Biological samples were processed
      using a combination of acid pretreatment and liquid-liquid extraction with
      verapamil used as the internal standard. This method produced a linear response
      throughout the indinavir concentration range of 0.05-30 microM in plasma and 0.05
      2.5 microM in CSF and brain with a LOD of 12.5 nM for plasma and CSF, and 6.25 nM
      for brain homogenate. Due to its high sensitivity, this assay is particularly
      useful for the quantitative determination of indinavir concentrations in brain
      and CSF.

PMID- 16605080
TI  - Simultaneous determination of paclitaxel and a new P-glycoprotein inhibitor HM
      30181 in rat plasma by liquid chromatography with tandem mass spectrometry.
AB  - An LC-MS/MS method for the simultaneous determination of a new P-glycoprotein
      inhibitor 4-oxo-4H-chromene-2-carboxylic acid [2-(2-(4-[2-(6,7-dimethoxy-3,4
      dihydro-1H-isoquinolin-2-yl)-ethyl]-phenyl)-2H-tetrazol-5-yl)-4,5-dimethoxy
      phenyl]-amide (HM-30181) and a P-glycoprotein substrate paclitaxel in rat plasma
      was developed to simultaneously evaluate the pharmacokinetics of paclitaxel and
      HM-30181 in the rats. HM-30181, paclitaxel, HM-30059 (internal standard (I.S.)
      for HM-30181), and docetaxel (I.S. for paclitaxel) were extracted from rat plasma
      with methyl-tert-butyl ether and analyzed on an Atlantis C18 column (5 microm,
      2.1 x 100 mm) with the mobile phase of ACN/10 mM ammonium formate (75:25 v/v).
      The analytes were detected using an ESI MS/MS in the multiple reaction monitoring
      (MRM) mode. The standard curves for HM-30181 and paclitaxel in plasma were linear
      (r > 0.999) over the concentration range of 2.0-500 ng/mL with a weighting of
      1/concentration2. The method showed a satisfactory sensitivity (2 ng/mL using 50
      microL plasma), precision (CV: < or = 6.6%), accuracy (relative error: -6.3 to
      2.0%), and selectivity. This method was successfully applied to the
      pharmacokinetic study of HM-30181 and paclitaxel in rat plasma after oral
      coadministration of paclitaxel and HM-30181 to male Sprague- Dawley rats.

PMID- 16605081
TI  - 2,6-Dimethyl-4-quinolinecarboxylic acid N-hydroxysuccinimide ester: a fluorogenic
      hydrophilic derivatizing reagent for liquid chromatographic analysis of aliphatic
      amines.
AB  - The use of a fluorogenic, hydrophilic, and amine-reactive reagent, 2,6-dimethyl-4
      quinolinecarboxylic acid N-hydroxysuccinimide ester (DMQC-OSu) has been
      investigated in the procolumn derivatization for the LC separation of aliphatic
      amines. In pH 8.0 aqueous medium, DMQC-OSu reacted with amines at 50 degrees C
      within 20 min to form highly fluorescent carboxamides and the excess reagent
      hydrolyzed to the corresponding carboxylic acid. The separation of representative
      amine derivatives with DMQC-OSu has been performed using a C18 column with the
      fluorescence detection at 326/409 nm. The detection limits reached nanomolar
      level. The proposed method has been applied to the analysis of real samples with
      recoveries of 94-108%. Compared with other succinimidyl esters used in the
      derivatization of amino compounds, DMQC-OSu and its hydrolysate had negligible
      fluorescence (phi(fl) = 0.09 and 0.02, respectively), which implied that small
      peaks appeared in chromatograms and slight interference was introduced to the
      determination.

PMID- 16605082
TI  - Development and validation of HPLC methods for the analysis of phenethylamine and
      indoloquinazoline alkaloids in Evodia species.
AB  - The aim of this study was to evaluate the chromatographic performance of a PEG
      stationary phase, in comparison with those of C18 columns, for the HPLC analysis
      of phenethylamine ((+/-)-synephrine) and indoloquinazoline (rutaecarpine and
      evodiamine) alkaloids in methanolic extracts of fruits of Evodia rutaecarpa
      (Juss.) Benth. and E. rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang
      (i.e., E. officinalis Dode) (Rutaceae family). The method was validated and
      showed good linearity, precision, accuracy, sensitivity, and specificity. The
      highest content of both phenethylamine and indoloquinazoline alkaloids was found
      in methanolic fruit extracts of E. rutaecarpa, and it was closely related to the
      degree of maturity. E. officinalis fruits displayed low amounts of both types of
      alkaloids. Furthermore, an enantioselective HPLC method for the enantioseparation
      of (+/-)-synephrine from Evodia fruits was applied, by using a protein-based
      chiral stationary phase with cellobiohydrolase (CBH) as the chiral selector
      (Chiral-CBH). Isolation of synephrine from Evodia aqueous fruit extracts was
      carried out by strong cation-exchange SPE. The results of the application of the
      method to the analysis of Evodia samples showed that (-)-synephrine was the main
      component while (+)-synephrine was present in low concentration.

PMID- 16605083
TI  - Determination of telmisartan in rat tissues by in-tube solid-phase
      microextraction coupled to high performance liquid chromatography.
AB  - A poly(methacrylic acid-ethylene glycol dimethacrylate, MAA-EGDMA) monolithic
      capillary was used for the direct and on-line extraction of telmisartan from
      Sprague-Dawley rat tissue (heart, kidney, and liver) homogenates. Under optimized
      conditions, the tissue homogenates were simply diluted with a mixture of
      phosphate buffer (pH 2)/ACN (90:8 v/v), and then injected for extraction only
      after centrifugation and filtration. Coupled to HPLC with fluorescence detection,
      the method was linear over the range of 1.25-1500 ng/g for telmisartan in heart
      and kidney, 12.5-15 000 ng/g in liver with correlation coefficients over 0.9992.
      The detection limits were found to be in the range from 0.24 to 1.8 ng/g. RSDs
      for intra- and inter-day ranged from 1.2 to 8.1%. The determination of
      telmisartan in treated rat tissues was achieved by using the proposed method.

PMID- 16605084
TI  - A preparative isolation and purification of arctigenin and matairesinol from
      Forsythia koreana by centrifugal partition chromatography.
AB  - Centrifugal partition chromatography was applied to separate arctigenin and
      matairesinol from Forsythia koreana extract with a two-phase solvent system
      composed of n-hexane-ethyl acetate-methanol-water (5:5:5:5 v/v). Using this
      method, arctigenin and matairesinol were successfully separated from partially
      purified F. koreana extracts in only one step. The purities of isolated compounds
      were determined to be over 90% by HPLC analysis.

PMID- 16605085
TI  - Determination of major carotenoids in vegetables by capillary
      electrochromatography.
AB  - A simple and rapid method for the isocratic separation and determination of
      carotenoids (carotenes and xanthophylls) in vegetables by CEC is described. The
      capillary column (100 microm ID, 25 cm effective length) was packed with 3 microm
      Hypersil ODS particles. The optimized mobile phase contained 60% ACN, 35% THF and
      5% of a 5 mM Tris aqueous buffer of pH 8. beta-Carotene, lycopene and lutein were
      separated with efficiencies of 66 000-128 000 plates/m within a short time (less
      than 12 min for the last peak eluted, 13/13'-cis-beta-carotene). An excellent
      resolution of the three carotenoids, as well as partial resolution of their
      geometrical isomers, was achieved. Application to the determination of the
      analytes in carrot, tomato, spinach and corn was demonstrated.

PMID- 16605086
TI  - Microemulsion electrokinetic chromatography for separation and analysis of
      curcuminoids in turmeric samples.
AB  - Microemulsion EKC (MEEKC) was developed for quantitative analysis of
      curcuminoids, such as curcumin (C), demethoxycurcumin (D), and bis
      demethoxycurcumin (B). MEEKC separation of curcuminoids was optimized, and a
      change in resolution was explained using a modified equation for resolution in
      MEEKC without electroosmosis. The suitable MEEKC conditions for separation of
      curcuminoids were obtained to be the microemulsion buffer containing 50 mM
      phosphate buffer at pH 2.5, 1.1% v/v n-octane as oil droplets, 180 mM SDS as
      surfactant, 890 mM 1-butanol as cosurfactant, and 25% v/v 2-propanol as organic
      cosolvent; applied voltage of -15 kV; and separation temperature 25 degrees C.
      Achieved baseline resolution of C:D and D:B was obtained with R(s) -2.4 and
      analysis time within 18 min. In addition, high accuracy and precision of the
      method were obtained. This MEEKC method was used for quantitative determination
      of individual curcuminoids in medicinal turmeric capsules and powdered turmeric
      used as coloring additive in food, with simple sample preparation such as solvent
      extraction, dilution, and filtration, and without cleaning up by SPE.

PMID- 16605087
TI  - Indirect laser-induced fluorescence detection of diuretics separated by capillary
      electrophoresis.
AB  - Indirect LIF detection was applied to the detection of four acidic diuretics
      separated by CZE. Semiconductor laser was employed to provide the stable
      excitation of 473 nm. With an optimized electrophoretic buffer system which
      contained 5 mM of triethylamine, 0.1 microM of fluorescein, and 5% of n-butanol,
      fast separation of four diuretics (ethacrynic acid, chlorthalidone,
      bendroflumethiazide, and bumetanide) can be performed within 3 min with the
      detection limits of 0.2-2 microg/mL. The impacts of buffer components including
      the concentrations of the electrolytes, fluorescence probe, and the organic
      additives were demonstrated. The method was applied for the detection of
      diuretics in urine. As an alternative way for the fast analysis of diuretics,
      this indirect detection method provided the technical support for future
      microchip performances, in which diuretics may be detected in the microchip by
      the common LIF detector without derivatization.

PMID- 16605088
TI  - Oscillatory transverse electric field enhances protein resolution and capacity of
      size-exclusion chromatography.
AB  - Protein separations by a novel size-exclusion electrochromatography (SEEC) are
      presented. The present SEEC, denoted as pSEEC, was established with an
      oscillatory low-voltage electric field perpendicular to the mobile-phase
      streamline. Retention experiments with different proteins indicated that the
      influence of electric field strength on the partition coefficient is different
      for different proteins as well as for the same protein under different mobile
      phase conditions. These results of protein retention led to the experimental
      design of protein separations with binary mixtures of BSA and immunoglobulin G
      (IgG), myoglobin (Myo) and lysozyme (Lys), as well as ovalbumin (Oval) and Myo.
      The separation results for the binary protein systems sufficiently exhibited the
      applicability of the pSEEC for various separations in terms of their molecular
      weights (MWs) as well as pIs. For example, it was possible to separate the gel
      excluded proteins (BSA/IgG) as well as gel-permeable and similar-molecular-weight
      proteins (Myo/Lys) by the pSEEC. Moreover, in the cases of Oval/ Myo, which could
      be partially separated by size-exclusion chromatography, the use of the pSEEC
      greatly improved the resolution and the separation became possible at high sample
      loading. The results indicate that the pSEEC technology is promising for
      preparative protein separations.

PMID- 16605089
TI  - Semipreparative-scale gas-chromatographic separation of filbertone enantiomers.
AB  - The enantioselectivity of heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl
      beta-CD) toward racemic filbertone (E-5-methyl-hep-2-en-4-one) was studied by
      performing the chiral separation on a capillary column, a thick-film wide-bore
      column and a semipreparative column. The semipreparative enantioseparation of
      filbertone was achieved at 80 degrees C by using a packed column providing (R)-
      and (S)-enantiomers of filbertone with ee 90 and 96%, respectively. The isolated
      enantiomers (approximately 250 microg each, ee = 90-96%) may be used for studies
      on the relationship of chirality and biological activity by olfactory screening
      and toxicological studies.

PMID- 16605090
TI  - Fast capillary GC using a low thermal mass column oven for the determination of
      residual solvents in pharmaceuticals.
AB  - A low thermal mass column oven was used for fast capillary GC analysis (high
      throughput) of residual solvents in pharmaceutical products. A dedicated
      capillary column, 20 m L x 180 microm ID x 1 microm DB-624 was programmed from 35
      degrees C (30 s) to 150 degrees C at 100 degrees C/min and to 250 degrees C (30
      s) at 200 degrees C/min, resulting in a total GC cycle time of less than 4 min.
      Complete separation of a target 20-component mixture was achieved, while method
      performance in terms of repeatability, sensitivity, and linearity was maintained
      in comparison to the generic method currently applied in our laboratories.

PMID- 16605091
TI  - Isolation and purification of canthaxanthin from the microalga Chlorella
      zofingiensis by high-speed counter-current chromatography.
AB  - Certain microalgae are considered to be a potential source of canthaxanthin,
      which possesses strong antioxidant and anticancer activities. A high-speed
      counter-current chromatography (HSCCC) method was developed for the separation
      and purification of canthaxanthin from the microalga Chlorella zofingiensis. The
      crude canthaxanthin was obtained by extraction with organic solvents after the
      microalgal sample had been saponified. Preparative HSCCC, with a two-phase
      solvent system composed of n-hexane-ethanol-water (10:9:1 v/v), was successfully
      performed yielding canthaxanthin at 98.7% purity from 150 mg of the crude extract
      (2.1% canthaxanthin) in a one-step separation. The recovery of canthaxanthin was
      92.3%. This was the first report that canthaxanthin was successfully separated
      and purified from microalgae.

PMID- 16605092
TI  - Assay for the simultaneous determination of guanidinoacetic acid, creatinine and
      creatine in plasma and urine by capillary electrophoresis UV-detection.
AB  - Guanidinoacetic acid (GAA) measurement has recently become of great interest for
      the diagnosis of creatine (Cn) metabolism disorders, and research calls for rapid
      and inexpensive methods for its detection in plasma and urine in order to assess
      a large number of patients. We propose a new assay for the measurement of GAA by
      a simple CZE UV-detection without previous sample derivatization. Plasma samples
      were filtered by Microcon-10 microconcentrators and directly injected into the
      capillary, while for urine specimens a simple water dilution before injection was
      needed. A baseline separation was obtained in less than 8 min using a 60.2 cm x
      75 microm uncoated silica capillary, 75 mmol/L Tris-phosphate buffer pH 2.25 at
      15 degrees C. The performance of the developed method was assessed by measuring
      plasma creatinine and Cn in 32 normal subjects and comparing the data obtained by
      the new method with those found with the previous CE assay. Our new method seems
      to be an inexpensive, fast and specific tool to assess a large number of patients
      both in clinical and in research laboratories.

PMID- 16605093
TI  - The Kansas Health Education Training Center: caring for the underserved.
AB  - The State of Kansas was awarded Health Education Training Centers (HETC)
      DHHS/HRSA, BrHPr Federal funds for the first time in 2002 through 2005. The three
      year grant award was under the leadership of the Nurse-Midwifery Education
      faculty of the University of Kansas (KU) School of Nursing. Federal objectives
      included: 1. To facilitate interdisciplinary clinical training for health
      professions students from nursing, medicine, and allied health at targeted
      underserved communities. 2. To deliver culturally appropriate health care
      information to underprivileged populations at targeted underserved communities.
      3. To conduct continuing education activities for community health workers and
      health professionals serving vulnerable urban and rural populations. 4. To
      recruit and mentor high school students from disadvantaged populations to pursue
      health professions. This three-year state-wide program addressed access to
      quality health care for underprivileged and underserved populations in select
      communities to improve health status, through community-based care that is
      culturally competent, multidisciplinary, sensitive to needs of special
      populations and augmented by health professions students. This article provides a
      review of two selected community-based interventions in Sedgwick and Wyandotte
      counties (addressing BrHPr federal objectives one and two) implemented to enhance
      care for immigrant pregnant women and underserved patients diagnosed with
      diabetes, respectively. Also included is a review of literature related to the
      efficacy and utilization of community based health workers (CHWs) in caring for
      vulnerable populations.

PMID- 16605094
TI  - Patient care survey of Kansas registered nurses.

PMID- 16605095
TI  - Culex neavei Theobald, as a possible transmitter of Hepatozoon matruhensis to the
      Egyptian snake Psammophis schokari.
AB  - Stained smears of Culex neavei females infected with Hepattozoon matruhensis from
      Psammophis schokari and kept at 20 +/- 1 degrees C showed the complete
      developmental stages of the parasite. However, no detection of sporozoites was
      monitored when females were kept at 30 +/- 1 degrees C. A successful infection of
      P. schokari was carried out in the laboratory by C. neavei bites. The effect of
      infection on the mosquito longevity was insignificant (p>0.05) under low
      temperature and highly significant (p<0.001) under high temperature. The
      mortality rate was slightly affected at 20 +/- 1 degrees C, but greatly affected
      at 30 +/- 1 degrees C.

PMID- 16605096
TI  - Detection of protozoal parasites in the stools of diarrhoeic patients using
      different techniques.
AB  - A total of 300 children were selected. A total of 180 apparently healthy children
      were selected. Each child was given a numerical number and subjected to a medical
      questionnaire. The rate of infection by the enteric protozoa detected by the four
      techniques revealed that G. lamblia reached 11.0% by concentration-sedimentation
      method, 10.3% by Sheather's concentration method and 7.0% (cysts) and 1.7%
      (vegetative) by direct wet smear. E. histolytica was 3.3% & 3.7% by the two
      concentration methods respectively. By direct wet smear 2.3% (cysts) and 0.7%
      (vegetative) were detected. E. coli was 7.3% & 7.0% by the two concentration
      methods respectively. By the direct wet smear 5.0% (cyst) and 0.3% (vegetative)
      were detected. Modified Zeihl-Nelsen stain demonstrated 9 cases of C. parvum
      (3.0%). Mallory and Iron haematoxylin gave the good characterristic colour for G.
      lamblia, E. histolytica, and E. coli followed by Trichrome. It was worthy to
      mention that direct smear method detected the low infections' percentage of all
      the intestinal target parasites in comparison with the four staining techniques.

PMID- 16605097
TI  - Cytogenetic studies of Calliphora vicina and Lucilia sericata (Diptera:
      Calliphoridae) from northwestern Egypt.
AB  - The blow fly, Calliphora vicina (Robineau-Desvoidy, 1830) and the green bottle
      fly, Lucilia sericata (Meigen, 1826) were collected from the north coast of
      Egypt. The karyotype of both flies was characterized by cytotaxonomical methods,
      including chromosome number, shape, relative length, arm ratio, centromeric index
      and designation. To quantify relative chromosome length, the percent of total
      haploid autosomal complement length (%TACL) for each autosome was calculated. The
      deploid number of chromosomes, of both flies, is 2n=12 where females have XX and
      males have XY sex determination mechanism. C. vicina have four metacentric
      autosomal pairs, with variable arm ratios, and one submetacentric pair. Both X &
      Y chromosomes are metacentric whereas X chromosome is the longest chromosome in
      the designation. The karyotype of L. sericata is characterized by the first
      autosome which is somewhat longer than all other chromosomes (%TACL=27.02). The
      autosomes of L. sericata are four metacentric pairs and one submetacentric pair.
      X & Y chromosomes are metacentric & submetacentric, respectively.

PMID- 16605098
TI  - Influence of amphibian and reptile on the feeding preference, longevity and
      reproductive capacity of Egyptian Culex (Culex) pipiens Linneaus (Diptera
      Culicidae).
AB  - Using Bufo regularis and ten reptile species as hosts for Culex pipiens under
      laboratory conditions revealed a great effect on feeding preference as a
      significant long feeding periods together with a significant reduction in the
      blood meal ratios were recorded. Female mosquitoes offered the experimental
      animals showed a short life span with different significant levels. A
      recognizable reduction in the reproductive fitness of Cx. pipiens females was
      recorded. Delayed oviposition and low ICI values was obtained. The percentage of
      egg hatching was not affected by the experimental animals.

PMID- 16605099
TI  - The clinical picture of hepatitis C virus as a concomitant infection with
      fascioliasis.
AB  - Hepatitis C and human fascioliasis are two of the most important public health
      problems locally and internationally. Each one has its own complications
      regarding spreading to man, clinical picture, laboratory and serologic diagnosis,
      treatment and prevention. Concomitant human infection with both magnified the
      complications. Clinically, both diseases (HCV and fascioliasis) have their own
      broad signs and symptoms. In concomitant infection, the clinical pictures of both
      showed some variations. The most common feature in fascioliasis and HCV patients
      was easy fatigability in 78.6% and the lowest was 7.18% for each of tympanic
      abdomen, tender colon, tender right upper quadrant, itching, arthritis, epi
      gastric pain, and right quadrant pain. The eosinophilia % ranged from 5-24 and
      the haemoglobin ranged from 7-11.1 gm/dl. In patients with fascioliasis alone,
      the most come feature was pallor in 96.15% and the lowest was 3.85% for each of
      splenomegaly, ascites and itching. Eosinophilia % ranged from 1 to 22 and
      haemoglobin ranged from 6-12 gm/dl. In general, the double infection with both
      HCV and fascioliasis magnified the laboratory and clinical pictures of such
      patients.

PMID- 16605100
TI  - Patients with gastrointestinal complains due to enteric parasites, with reference
      to Entamoeba histolytica/dispar as dected by ELISA E. histolytica adhesion in
      stool.
AB  - A total of 210 patients with gastrointestinal troubles, of both sex and a mean
      age of 32 +/- 6.1 years, selected from the outpatient's clinics of Al-Azhar
      University Hospitals. 115 (54.76%) had dysentery, 95 (45.23%) did not have
      dysentery, 15 (14%) suffered flatulence, 20 (9.52%) had epi-gastric pain, 19
      (9.05%) had vague abdominal pain, 5 vomiting (5.2%) and 10 (4.9%) had fever. Two
      symptoms were in 29 (13.81%) patients and three symptoms in 12 (5.71%). Of the
      210 patients, 20 (9.9%) had helminthes infection, 121 (57.6%) had intestinal
      protozoa and 69 (32.9%) had no parasitic infection. Of these parasite-free
      patients, 16 had Shigella sp. and nine had Campylobacter sp. Of the patients with
      intestinal protozoa, 34 (16.2%) had E. histolytica/dispar by stool examination of
      stained smears. By using ELISA for detection of E. histolytica adhesion in stool
      samples of 115 with diarrhea only 18 had true E. histolytica infection and of 3
      without diarrhea only one had E. histolytica infection. Mean-while, ELISA did not
      cross-reacted E. coli, Giardia lamblia, Cryptosporidium parvum, Endolimax nana or
      Blastocystis hominis. So, ELISA for detection of E. histolytica adhesion in stool
      samples was more specific than microscopy and safe direction to the E.
      histolytica treatment. Apart from intestinal protozoan and bacteria, helminthes
      were seen in stool analysis. These were Schistosoma mansoni (0.95%), Capillaria
      sp. (0.95%), Enterobius vermicularis (1.90%) macroscopically, Hymenolepis nana
      (4.3%) and Ascaris lumbricoides (1.43%).

PMID- 16605101
TI  - Effect of some immunomodulators on the host-parasite system in experimental
      Hymenolepiasis nana.
AB  - Mice experimentally infected with H. nana and injected with immunosuppressant
      {cyclophosphamide (Cp) and lead nitrate (Ln)} showed significant increase in
      infection intensity, significant decrease in intestinal mast cell count,
      dissemination of larvae to the liver, toxic hepatitis and absence of specific
      serum IgG. Cyclophosphamide caused morphological abnormallities in adult worms,
      prolongation of patent period and more severe villous changes. Immuno-stimulants
      represented by Levamisol (Lv) and gamma interferon (IFN-alpha) caused significant
      decrease in infection intensity, significant shortening of patent period and
      early improvement of histopathological changes. Immunostimulants, particularly
      IFN-alpha, were highly effective in counteracting hyperinfection seen with immuno
      suppression. The study confirmed the deleterious effects of immunosuppression on
      hymenolepiasis and suggested a beneficial role for immunotherapy for
      immunosuppressed patients.

PMID- 16605102
TI  - A preliminary pilot survey (Culex pipiens), Sharkia Governorate, Egypt.
AB  - Sixteen different ecological areas in Sharkia Governorate were surveyed for adult
      Culex pipiens. The prevalence was investigated among 160 houses of 2800
      individuals and their surrounding outdoors. The collected adults were 41488 from
      October 2003 to November 2004. The collection rates were higher in the rural
      areas than urban ones. Mosquitoes were common all the year round except January,
      February and March, with peaks in summer and autumn than in spring and winter.
      Larvae in descending order were Cx. pipiens the predominant larva followed by Ae.
      caspius, Culiseta sp. and then Cx. pusillus. Cx. pipiens was described as the
      most common larva.

PMID- 16605103
TI  - Studies on rodents role as reservoir hosts of leishmaniasis with specical
      reference to their ectoparasites in Suez Governorate.
AB  - The distribution of rodents was studied in three different habitats. Seven rodent
      species were identified: Rattus norvegicus, R. alexandrinus, R. frugivorous, Mus
      musculus, Acomys russatus, Meriones sacramenti and Gerbillus pyramidum. The
      species distribution varied with the habitat type. The highest density of rodents
      was in July and August and the lowest one was in January. However, some species
      were collected all the year round. The rodents were investigated for the endo-
      and ecto-parasites. No Leishmania parasites were found. The ectoparasites were:
      Xenopsylla cheopis, Leptopsylla segnis and Ctenocephalides felis, Polyplax
      spinulos, Hyalomma dromedarii (nymph) and Echinolaelaps echidninus and
      Hemolaelaps glassgowi. Ecto-parasites were on rodents all year-round in domestic
      habitat and peridomestic habitats. In wild one, ecto-parasites activity was from
      March to December. The rodents' role as reservoir for L. major was experimentally
      studied. Rodents inoculated with L. major together with hamster and BALB-c mice
      developed cutaneous lesions. The active lesions, the rodents' ecological habitats
      and the presence of insect-vector may pave the way to an epidemic zoonotic
      leishmaniasis role.

PMID- 16605104
TI  - Cryptosporidiosis among children in Tripoli.

PMID- 16605105
TI  - Present situation of house dust mites in Dakahlia Governorate, Egypt.
AB  - House dust mites are common inhalant allergens, which can precipitate atopic
      disease episodes. The present study revealed presence of four mites. These are
      Dermatophagoides farinae, D. pteronyssinus, Acheles gracilis and Ornithonyssus
      bacoti. Population densities of different live adult mites were investigated in
      different house habitats. In urban houses, pyroglyphid mites were the predominant
      in bedrooms and D. farinae was the most abundant. A. gracilis was more abundant
      in living rooms followed by D. farinae then D. pteronyssinus. A. gracilis was the
      most prevalent in kitchens. While in rural houses, O. bacoti was the most
      abundant species followed by pyroglyphid mites. Since Dermatophagoides species
      and A. gracilis were present in numbers high enough to allow their ecological
      consideration, their seasonal abundance in urban bed-rooms was investigated and
      revealed that both D. farinae and D. pteronyssinus have two peaks of abundance,
      one slightly higher in spring and the second in autumn. A. gracilis has two peaks
      but the higher occurred in autumn and the second in spring.

PMID- 16605106
TI  - Ecology, biology and susceptibility of Phlebotomus papatasi to Leishmania
      experimental infection in Suez Governorate.
AB  - Zoonotic cutaneous leishmaniasis (ZCL) is endemic in Sinai Peninsula. The sand
      fly and reservoirs were investigated in Suez G., since new settlements and land
      reclamation programs are ongoing. The results showed that Phlebotomus papatasi
      reached its highest density in September. The successfully colonized P. papatasi
      facilitated its biology and competence study. An autogenous trait was proven
      within P. papatasi population indicating its ability to survive and breed during
      adverse conditions. The vector competence was carried out under laboratory
      condition through feeding on lesion of a L. major experimentally infected hamster
      and by membrane feeding technique. Both hamsters and BALB-c mice inoculated with
      L. major developed ZCL lesions.

PMID- 16605107
TI  - Molecular identity of the electrophoretic pattern and the major cross-reacting
      immunogens of Toxoplasma gondii (RH strain) and Neospora caninum.
AB  - The complex electrophoretic profile of the antigenic components of Toxoplasma
      gondii and Neospora caninum was studied. T. gondii (RH strain) trophozoite's
      antigens were resolved by gel electrophoresis under denaturating condition.
      Resolved polypeptides were tested by immunoblotting against hyper-immune serum
      prepared in Boscat rabbits. Immunoblot analysis revealed 6 reactive bands, which
      are 158, 111, 102, 86, 55 and 33 kDa, out of 10 antigenic bands of the parasite.
      Concerning N. caninum trophozoite's antigens, immunoblot analysis revealed 5
      reactive bands, which are 159, 119, 106, 97 & 39 kDa, out of 8 antigenic bands of
      the parasite. Cross reactivity trials between the 2 parasites explore 3 cross
      reactive bands, indicating high antigenic similarity in between.

PMID- 16605108
TI  - An ultrastructural study on Desportesius invaginatus (Nematoda, Acuariidae) from
      Ardeola ibis ibis in Egypt.
AB  - The present study is undertaken to describe the ultrastructure of Desportesius
      invaginatus (Nematoda, Acuariidae) for the first time in Egypt showing details
      that were not clearly defined before. This nematode is found in the
      proventriculus of Ardeola ibis ibis. The latter is known in Egypt as "Abu Erdan"
      and it is a very common and useful bird to Egyptian farmers. The pathogenecity of
      this nematode within their host was observed. The presence of such high number of
      worms raised the curiosity of the present author to see if they had the potential
      to cause any harm to such economically important birds to Egyptian farmers.

PMID- 16605109
TI  - The adjuvant effects of IL-12 and BCG on autoclaved Leishmania major vaccine in
      experimental cutaneous leishmaniasis.
AB  - Cutaneous leishmaniasis is a universal disease causing skin ulceration and
      deformity. A reliable vaccine remains to be a possible practical means of
      control. The amastigotes multiply intracellulary in macrophages provoking a cell
      mediated type of immune response. IL-12 is the central cytokine of CMI. It is
      produced by sensitized macrophages, stimulates both Th1 and NK cells to secrete
      IFN-gamma which in turn activates the intracellular killing of Leishmania in
      macrophages via increased oxygen radicals. This work aimed mainly at studying the
      adjuvant effect of IL-12 on autoclaved L. major (ALM) vaccine, compared to that
      of BCG in L. major infection. The material included five groups of Swiss albino
      mice; the test group infected after receiving ALM+IL-12, a non-infected control
      group, and three other control groups infected after receiving ALM+BCG, IL-12
      alone and BCG alone L. major was cultured to provide promastigotes for vaccine
      and infection. The measured parameters included the lesion size, type and
      progress; the parasite density and the level of IFN-gamma in serum. The results
      showed that the best protection against challenge infection was obtained by ALM +
      IL-12 followed by ALM + BCG. The former is recommended for use as a vaccine with
      regards to its proved efficacy and known safety.

PMID- 16605110
TI  - INF-gamma, IL-5 and IgE profiles in chronic schistosomiasis mansoni Egyptian
      patients with or without hepatitis C infection.
AB  - The immune response against clinical forms of chronic schistosomiasis mansoni
      patients with or without HCV infection was evaluated by assays the serum levels
      of IFN-gamma and IL-5 for estimate the cell mediated immunity and IgE level to
      estimate the humoral immunity. This study included three patient groups. G.I
      included 25 patients with intestinal schistosomiasis, G.II included 15 patients
      with hepatosplenic schistosomiasis and G.III included 40 patients hepatosplenic
      schistosomiasis co-infected with HCV. Control G.IV included 15 healthy persons
      with matched age and sex. The intestinal group had high IFN-gamma (92%), normal
      level of IL-5 and IgE. The immune response was mainly 100% Th-1 response. The
      hepatosplenic patients had high IFN-gamma (26.7%), IL-5 (86.7%) and IgE (73.3%).
      The immune response was 73.4% Th-0, 13.3% Th-1 and 13.3% Th-2. The co-infected
      group had high IFN-gamma (62.7%), IL-5 (100%) and IgE (92.5%). The immune
      response was 62.5% Th-0 and 37.5% Th-2 immunity. The shift to Th-0 and Th-2
      immunity as well as associated depression of Th-1 in mixed group of patients may
      be playing a role in the persistence and severity of both diseases. Such immunity
      defects add to decrease challenge against HCV clearance.

PMID- 16605111
TI  - Parasitological, hematological and ultrastructural study of the effect of COX-2
      inhibitor, pyocyanin pigment and praziquantel, on S. mansoni infected mice.
AB  - The effect of cyclooxygenase-2 (COX-2) inhibitor, such (as meloxicam, and
      pyocyanin pigment of Pseudomonas aeruginosa) with and without praziquantel (PZQ)
      on worms, ova count, bone marrow and blood cells in 7 groups of Schistosoma
      mansoni infected mice was studied. The results revealed significant decrease of
      worm burden and ova count in all treated groups as compared to the infected
      untreated group, while those with combined treatment of PZQ and meloxicam or
      pyocyanin showed complete eradication of the worm with the highest reduction in
      the tissue egg load. EM showed extensive swelling and vesiculation of the
      tegument, completely implanted spines that overlie degenerated muscle layer were
      obvious in groups treated with either meloxicam or pyocyanin. Hematological study
      revealed significant increase (P<0.05) of total leucocytic count of PZQ treated
      group while that treated with either meloxicam or pyocyanin showed significant
      decrease (P<0.05), but in combination of PZQ with meloxicam or pyocyanin no
      significant difference as compared to the infected untreated group. The
      neutrophil was the main cell affected in groups treated with neither meloxicam
      nor pyocyanin alone with significant decrease (P<0.05), but with significant
      increase (P<0.05) in combination with PZQ as compared to the infected untreated
      group. Those treated with PZQ plus meloxicam showed significant increase as
      compared to that plus pyocyanin. Eosinophil count showed significant decrease
      (P<0.05) in all treated groups as compared to the infected untreated group.
      Inverse correlation between serum level of sFas and peripheral neutrophil count
      was detected. Ultrastructural study of the bone marrow explained the results as
      groups treated with meloxicam revealed dissociation between nuclear and
      cytoplasmic development in the neutophils with cytoplasm maintaining primitive
      appearance despite maturation of the nucleus, that is manifested by the
      persistent production of immature granules and the still orientation of Golgi
      cternae and the centriole around the nucleus. Groups treated with pyocyanin
      pigment revealed many abnormalities in neutophils as hypogranularity or early
      apoptotic morphology changes as intense perinuclear chromatin aggregation or
      nucleus fragmentation. In peripheral blood apoptotic morphology changes was
      detected in both groups treated with meloxicam or pyocyanin while most of cells
      of mice treated with PZQ were in an active state. Consequently, it is preferable
      to give meloxicam with PZQ for a short period of time (less side-effect) to
      eradicate S. mansoni worm completely but with continuous observation of the
      peripheral neutrophil count and function.

PMID- 16605112
TI  - Clinical significance of aflatoxin, mutant P53 gene and sIL-2 receptor in liver
      cirrhosis and hepatocellular carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) varies widely worldwide. Chronic
      infection with hepatitis B virus (HBV) and exposure to aflatoxins in foodstuffs
      are the main risk factors. AAG to AGT transversion at codon 249 of the P53 gene
      arg-ser (249ser) has been identified as a hotspot, reflecting DNA damage caused
      by aflatoxin B1 metabolites in HCC. Because HBV infection is often endemic in
      high aflatoxin exposure areas, it is still not clear whether HBV acts as a con
      founder or as a synergistic partner in the development of the 249ser P53
      mutation. Serum levels of soluble interleukin 2 receptor (sIL-2R) correlated with
      the progression of liver cirrhosis independently of its etiology. This fact may
      reflect the stimulation of T-lymphocytes, monocytes and macrophages in liver
      cirrhosis. The inter-relationship among aflatoxin exposure, HBV & HCV infections,
      P53 & sIL-2R in patients with liver cirrhosis and hepatocellular carcinoma was
      studied. The results revealed significant increase in serum levels of mutant P53,
      sIL-2R and aflatoxin B1 in patients with cirrhosis and those with HCC compared to
      the controls. HCC patients showed levels of all the three parameters
      significantly higher than both cirrhotics and controls (P<0.001). Correlations
      were found between serum aflatoxin B1, mutant P53 and sIL-2R in HCC group. The
      results were discussed.

PMID- 16605113
TI  - Laboratory studies on the possibility of Culex (Culex) pipiens l. to harbour and
      transmit Hepatozoon matruhensis to the Egyptian snake Psammophis schokari.
AB  - A successful experimental infection of Psammophis schokari snake with Hepatozoon
      matruhensis through Culex (Culex) pipiens bites was carried out under laboratory
      condition of 20 +/- 1 degrees C and 60-70 % R.H. The period monitored for
      gametocyte maturation ranged from 38 to 42 days while the recorded prepatent
      period ranged from 28 to 35 days. The effect of infection was nonsignificant on
      longevity, incubation period and percenttage of egg hatching (P>0.05). Meanwhile
      a significant increase (P<0.05) in the preoviposition period together with a
      significant reduction (P<0.001) in the number of eggs deposited of infected
      females were recorded.

PMID- 16605114
TI  - Studies on some biological aspects of Culex pipiens and Culex quinquefasciatus
      (Diptera: Culicidae) infected with Hepatozoon sp. harboured by the Saudian lizard
      Uromastyx microlepis.
AB  - Laboratory observations revealed that both C. pipiens and C. quinquefasciatus
      could harbour the parasitic Hepatozoon, while only Cx. pipiens succeeded to
      induce infection to the recipient lizard Uromastyx microlepis. A significant
      reduction in egg production together with a significant increase in the pre
      oviposition period of C. pipiens was recorded. Incubation period and percentage
      of egg hatching showed no significant changes. Infection had no effect on the
      reproductive fitness of C. quinquefasciatus. Haematin excretion was normally
      distributed for all both species. No size difference was recorded between
      infected and uninfected ones. Infection did not affect longevity.

PMID- 16605115
TI  - Some parasitic flukes infecting farm animals in Al-Santa Center, Gharbia
      Governorate, Egypt.
AB  - A total of 213 farm animals in the vicinity of Al-Santa Center (73 cattle, 90
      buffaloes and 50 sheep) were coprologic examined for natural infection with
      trematod-parasites. The results showed that cattle were infected with Fasciola sp
      (21.8%) and Paramphistomum sp. (7.3%), buffaloes were infected with Fasciola sp.
      (17.7%) and Paramphistomum sp. (10%), while sheep were infected with Fasciola sp.
      (30%), D. dendriticum (5%) and Paramphistomum sp. (4%). The three animal species
      were treated for paramphistomiasis with a total dose of 1800, 6000 and 7500 mgm
      of Oleo-resin solution of Commiphora molmol (dose of 6 ml of 10gm% equal to 2
      Mirazid. The cure was 100% in sheep 80% in cattle and 44.4% in buffaloes. High
      dose for both cattle and buffaloes to reach 100% cure rate was not tried.

PMID- 16605116
TI  - Study on human ophthalmomyiasis externa caused by Oestrus ovis larva, in Sirte
      Libya: parasite features, clinical presentation and management.
AB  - Oestrus ovis larva is by far the commonest cause of human ophthalmomyiasis. The
      larva usually limits it's activity to the conjunctiva and cornea, but,
      penetration of the eye is a potential complication. Misdiagnosis is common and
      the condition of acute catarrhal conjunctivitis is ascribed to other causes. The
      study included 20 patients referred to university hospital of Sirte, Libya.
      Results showed that the condition was more common among adult male shepherds and
      farmers in rural areas. Important criteria for diagnosis were; sudden mobile
      foreign body sensation with abrupt itching and lacrimation occurring in endemic
      area, in warm months even without history of fly strike. Effective treatment
      consisted of mechanical removal of the larva by the cotton swap mounting
      technique which resulted in rapid improvement. Suffocation of residual larvae was
      mediated by use of liberal amounts of topical antibiotics. Slit lamp examination
      of larva showed that it was small, translucent, avoid the light beam and easily
      overlooked. Detailed microscopic examination of larval surface structures
      revealed a multi-component attachment apparatus consisting of oral hooks, inter
      segmental spines, caudal spines and a multi-layered spiny thoracic complex
      described for the first time. These injurious structures are believed to be
      responsible through inflicting direct mechanical damage for the observed
      haemorrhage, ulceration or even the potential invasion, as these changes were
      more obvious in neglected cases. So, early diagnosis and treatment are essential
      to avoid complications.

PMID- 16605117
TI  - House dust mites and allergic manifestations among some children in Dammam, Saudi
      Arabia.
AB  - The house dust mites is (=HDM) still one of the many causes of allergy,
      particularly atopic dermatitis. In the houses of children who were suffering
      allergic manifestations as atopic dermatitis, respiratory allergy, bronchitis,
      skin rash and fever. Double manifestations with fever were reported in four
      children. In the present study, two types of mites were recovered,
      Dermatophagoides farinae and Ornithonyssus bacoti. The immunoglobulins (G., M.,
      A. & E) as well as complements (C3 & C4) were measured in the patients and cross
      matched controls. The complements did not show any significant difference among
      patients and controls. Elevation was detected in IgG and IgM, but not in IgA.
      However, high significant elevation was in IgE. The results were discussed on the
      light of regional work.

PMID- 16605118
TI  - Salivary gland composition of some Old World vector sand fly.
AB  - The saliva of blood feeding arthropods has a variety of substances that are
      responsible for blood meal success. The composition and the influence of sand fly
      saliva vary considerably between species and even between populations of
      different geographical origin. In Old-World sand flies (Phlebotomus sp.)
      differences in protein components of the salivary gland homogenate were
      demonstrated between species and between colonies of the same species. We
      compared protein components in the salivary glands of sand flies vectors from
      different species and origins. The salivary gland homogenate (SGH) of laboratory
      reared Egyptian phlebotomine sand flies, P. papatasi, P. sergenti and P.
      langeroni Sinai and El-Agamy strains respectively were compared with Spanish
      naturally caught P. perniciosus and P. ariasi, which were collected from a farm
      20 km southwest of Barcelona. Polyacrylamide gel electrophoresis (PAGE) (SDS
      PAGE) was done for compareson. The electrophoresis profiles of SGH differed
      between all tested species. From 8-14 prominent proteins bands with molecular
      masses ranging from 8-70 kDa were visualized by Commassie blue gel code staining
      in each SGH. So, saliva composition varied between species and sub-species, and
      increased between different sub-genera and geographical areas. The data are
      important for the characterization of salivary proteins.

PMID- 16605119
TI  - Examination of urine for bacteria and parasites among elder persons in the rural
      area, in Dammam District.
AB  - The asymptomatic bacteria and parasites in urines were studied in elder persons
      living in the rural areas of Dammam District. Complete history taking, clinical
      examination, urine analysis and culture, blood glucose level and haemoglobins in
      gm were performed for 43 elders of both sexes. The bacteria detected in urine in
      a descending order were Klebsiella sp. Staphyloccocus sp., Escherichia coli and
      Pseudomonas sp. The parasites detected were only Trichomonas vaginalis in three
      diabetic females. No doubt, regular urine examination is a must for the elders in
      rural areas.

PMID- 16605120
TI  - Effect of Commiphora molmol on adults, egg masses and egg-deposition of
      Biomphalaria arabica under laboratory conditions.
AB  - Commiphora molmol (Myrrh) has molluscicidal effect on Biomphalaria arabica snails
      at low concentration (40 ppm) after 48 hours exposure. The number of dead-snails
      increased with increasing the time of exposure. One day-old egg masses were more
      susceptible (death 100% with 80ppm) to the ovicidal effect of C. molmol than the
      five-day old ones (Death 95% with 80ppm). However, the eggs were more resistant
      to the C. molmol effect than the adult snails, embryogenesis began to stop at 20
      ppm and eggs were all killed at 60 & 80 ppm. B. arabica fecundity decreased at 1
      ppm. Based on safety to man and animals, C. molmol is recommended as a safe
      molluscidide.

PMID- 16605121
TI  - Influence of photon beam irradiation on Lymnaea natalensis snails infected with
      Fasciola gigantica.
AB  - Lymnaea natalensis is the intermediate host of Fasciola gigantica in Egypt. The
      effect of photon beam irradiation on the ability of the laboratory reared L.
      natalensis to support the larval development of F. gigantica has been studied.
      120 snails were divided into two groups: The control infected non irradiated
      group (GI) and the experimental infected irradiated group (GII). The later group
      was subdivided into two subgroups: GIIa: snails irradiated before infection and
      GIIb: snails irradiated after infection. Photon beam irradiation had non
      significant effect on the survival rate between the all groups at the 30th day
      post infection. The life span, the number of infected snails and the length of
      the shedding period were significantly decreased in the two irradiated subgroups
      than the control group. The effect was more obvious on GIIb without significant
      difference. The number of metacercariae significantly decreased in the 2
      irradiated subgroups than the control one. Also, it was significantly decreased
      in GIIb when compared with GIIa. So, photon beam irradiation has a great role on
      retarding larval development of F. gigantica inside the snail. This opens the way
      to a new strategy for fascioliasis control of in Egypt.

PMID- 16605122
TI  - Efficacy of Trigonella foenum-graecum (fenugreek) on third stage larvae and adult
      fecundity of Musca domestica.
AB  - The insecticidal efficacy of Trigonella foenum-graecum (fenugreek) on the 3rd
      stage larvae of Musca domestica and adult fecundity was evaluated under
      controlled laboratory conditions. The concentrations from 25% to 100% completely
      killed the larvae. 5%, 2% and 1% caused mortality percent of 44.4, 33.3 and 22.2
      respectively. Less concentration of fenugreek was not tried. On the other hand,
      the fecundity of the emerged adults was 20%, Zero% and 28.6%. On the other hand,
      only one control larva died and the nine emerged adults were fertile. So,
      fenugreek at low concentration not only has a larvicidal action against house fly
      larvae but also affected the adult fecundity.

PMID- 16605123
TI  - Immunomodulation of pulmonary and hepatic granulomatous response in mice
      immunized with purified lung-stage schistosomulae antigen.
AB  - The present objective was to investigate the possible effect of immunization
      protocol against Schistosoma mansoni infection using purified lung-stage
      schistosomulae antigen. Two experimental models (lung & liver) were used, each of
      3 groups (Gs): Immunized G. (10 mice) infected control G. (10 mice) and normal
      control G. (10 mice). Hundred microg of purified schistosomulae antigen followed
      by two booster doses each of 50 microg antigen and at one week interval were
      injected intraperitoneally into Swiss albino mice three days prior to intravenous
      injection of 3000 viable S. mansoni eggs (lung model) or to exposure to 100
      cercariae (hepatic model). Mice were sacrificed 16 days post-injection (lung
      model) and 8 weeks post-infection (hepatic model). Various parasitological
      parameters, histopathological assessments and immunological parameters were
      studied. The data revealed that immunization with purified lung-stage
      schistosomulae antigen induces protective effect against S. mansoni infection.
      The marked reduction in worm burden, egg load, granuloma diameter and collagen
      content were accompanied by increased percentage of degenerated ova and
      amelioration of the associated pathological changes in pulmonary and hepatic
      tissue. Increased levels of specific immunoglobulins particularly IgG & IgM and
      decreased ratio of T cell subsets (CD4+/CD8+) in granulomas of both models were
      also noticed.

PMID- 16605124
TI  - Application of adult worm and lung-stage antigens to immunize against Schistosoma
      mansoni using cytokines as adjuvants.
AB  - Different Schistosoma mansoni antigens; adult worm antigen (SWAP) and lung-stage
      antigen (SLAP) together with different cytokine adjuvants (Interferon-gamma and
      Interleukin-4) were used to immunize mice against. S. mansoni. Immunization
      program was directed towards the production of an intense immune response
      together with balanced T-helper1 and T-helper2 immune responses. The goal of
      immunization was not only to protect from infection but also to modulate the
      pathology inflicted by the parasite. Parameters like adult load, egg counts, anti
      Schistosoma antibody titers and liver pathology were used to evaluate the
      different immunization scheme. SLAP antigen has proven to be a better antigen not
      only in protection but also in pathology modulation. SLAP plus IFN-gamma as an
      adjuvant was the best immunization regimen with almost 50% protection and a
      remarkable resolving of parasite pathology. Unexpectedly, IL-4 had a weak but
      observed adjuvant protective effect. The results is a step in the path for a
      Schistosoma vaccine that guides the immune system towards a balanced response
      targeting the pathology induced by the parasite rather than the parasite itself.

PMID- 16605125
TI  - MITF and SgIGSF: an essential transcription factor and its target adhesion
      molecule for development and survival of mast cells.
AB  - MITF transcription factor is not produced in mutant mice of WBB6F1-Mitf(mi
      vga9/Mitf(mi-vga9). When bone marrow cells of normal WBB6F1-+/+ micewere
      transplanted to the irradiated WBB6F1-KitW/KitW-v mice, which are genetically
      mast cell deficient, erythrocytes, neutrophils, macrophages, B cells and T cells
      of the donor origin developed in the recipients. On the other hand, when bone
      marrow cells of WBB6F1-Mitf(mi-vga9/Mitf(mi-vga9) mice were transplanted to
      similarly irradiated WBB6F1-KitW/KitW-v mice, erythrocytes, neutrophils,
      macrophages, B cells and T cells of the donor origin developed but mast cells
      never appeared. To identify the targets of MITF, we elaborated a subtracted cDNA
      library between cultured mast cells (CMCs) derived from +/+ mice and CMCs from
      MITF mutant mice. We obtained a clone encoding SgIGSF, which was expressed on the
      adhesion surface of +/+ CMCs attaching to fibroblasts. CMCs of WBB6F1-Mitf(mi
      vga9/ Mitf(mi-vga9) mice did not express SgIGSF, did not attach to fibroblasts
      and did not survive in the peritoneal cavity of WBB6F1-KitW/KitW-v mice. When
      MITF or SgIGSF cDNA was transfected to WBB6F1-Mitf(mi-vga9/Mitf(mi-vga9) CMCs,
      they attached to fibroblasts and showed an improved survival in the peritoneal
      cavity of WBB6F1-KitW/KitW-v mice. MITF and SgIGSF appeared essential for the
      development and survival of mast cells in tissues of adult WBB6F1-KitW/KitW-v
      mice.

PMID- 16605127
TI  - The role of Src family kinases in mast cell effector function.
AB  - Src family protein tyrosine kinases (SrcPTK) play a central role in
      immunoglobulin E (IgE)-mediated activation of mast cells. Functional coupling of
      the high-affinity IgE receptor (FcepsilonRI) is initiated by the SrcPTK family
      member, Lyn, through an antigen aggregation-dependent transphosphorylation.
      Because Lyn is the 'initiating' kinase, an essential role in mast cell effector
      function was conferred. Recent studies challenge this view. Evidence
      demonstrating that Lyn kinase is dispensable for mast cell degranulation is now
      available. In contrast, another SrcPTK family member, Fyn, is required for
      degranulation and cytokine production. New studies, on mast cells expressing
      FcepsilonRIbeta ITAM mutants, show that the loss of Lyn interaction with
      FcepsilonRI has only a modest inhibitory effect on mast cell degranulation and an
      enhancing effect on lymphokine production, although many of the biochemical
      signals (including FcepsilonRI phosphorylation) were significantly impaired. In
      vivo studies on Lyn-null mice also demonstrated that this kinase is a negative
      regulator of IgE production and anaphylaxis, whereas Fyn kinase is required for
      anaphylaxis but not for IgE production. Collectively, these studies argue that
      sustained Lyn kinase activity negatively regulates mast cell responses. This
      suggests the possible existence of Lyn polymorphisms that may contribute in
      allergic disease.

PMID- 16605126
TI  - Immune sensitization in the skin is enhanced by antigen-independent effects of
      IgE on mast cells.
AB  - Contact sensitivity responses require both effective immune sensitization
      following cutaneous exposure to chemical haptens and antigen-specific elicitation
      of inflammation upon subsequent hapten challenge. We have observed that that
      antigen-independent effects of immunoglobulin E (IgE) antibodies promote immune
      sensitization to haptens in the skin. Contact sensitivity is markedly impaired in
      IgE-/- mice but can be restored by either transfer of sensitized cells from wild
      type mice or administration of hapten-irrelevant IgE before sensitization.
      Moreover, IgE-/- mice exhibit impairment in the emigration of dendritic cells
      from the epidermis after hapten exposure. Monomeric IgE has been reported to
      influence mast cell function. We observe diminished contact sensitivity in mice
      lacking FcepsilonRI or mast cells, and mRNA for several mast cell-associated
      genes is reduced in IgE-/- vs. wild-type skin after hapten exposure. We propose
      that levels of IgE normally present in mice favour immune sensitization via
      antigen-independent effects on mast cells.

PMID- 16605128
TI  - RasGRP4 in mast cell signalling and disease susceptibility.
AB  - The nucleotide sequences of the mouse, rat and human cDNAs and genes that encode
      the fourth member of the Ras guanine nucleotide releasing protein (RasGRP) family
      of signalling proteins have been deduced. RasGRP4 is a mast cell-restricted,
      cation-dependent, guanine nucleotide exchange factor (GEF). It is also a
      diacylglycerol (DAG)/phorbol ester receptor that plays a prominent role in
      dictating which protease and eicosanoid mediators are expressed in rodent and
      human mast cell lines. RasGRP4 appears to act downstream of the tyrosine kinase
      receptor c-Kt/CD117 and upstream of the basic-helix-loop-helix-leucine zipper
      transcription factor MITE Allelic variants of RasGRP4 have been identified, as
      have functionally different isoforms that are the result of variable splicing of
      its gene. Earlier gene-linkage studies revealed a site on chromosome 7A3-B1 that
      controls intrinsic airway reactivity to methacholine in backcrossed C3H/HeJ and
      A/J mice. The 18-exon mouse RasGRP4 gene resides on chromosome 7A3-B1, and recent
      studies revealed that the mast cells developed from the hyporesponsive C3H/HeJ
      mouse strain preferentially produce a defective isoform of RasGRP4. These and
      other data suggest that RasGRP4 is of critical importance in mast cell
      development and that the expression of abnormal isoforms of the protein can lead
      to mast cell dysfunction.

PMID- 16605129
TI  - Regulation of mast cell secretory response to the type I Fcepsilon receptor:
      inhibitory elements and desensitization.
AB  - While the current understanding of the stimulus-response coupling networks
      triggered by the multi-chain immune-recognition receptors (MIRRs) has markedly
      advanced, knowledge of its control mechanisms is only emerging. Regulation of the
      secretory response of mast cells to the stimulus provided by the type I Fcepsilon
      receptor (FcepsilonRI) is our topic of interest. Several mast cell membrane
      receptors capable of inhibiting both immediate and late responses have so far
      been identified. However, their ligands and mechanism(s) of operation are only
      partly known. Moreover, desensitization of mast cells' response to the
      FcepsilonRI, a well-known and widespread control process of many neural or
      hormone receptors, is hardly understood in this case. In this brief report we
      describe results of recent experiments in which we studied both of these aspects
      of mast cells' response to the FcepsilonRI stimulus by an inhibitory receptor
      MAFA, as well as those where we have established that these cells are susceptible
      to physiological modes of FcepsilonRI desensitization caused by prolonged
      exposure to sub-threshold concentrations of FcepsilonRI clustering agents.

PMID- 16605130
TI  - IgE regulation of mast cell survival and function.
AB  - Traditionally, it is thought that IgE binding to mast cells via the high-affinity
      receptor (FcepsilonRI) is simply a passive 'sensitization' step prior to
      activation by receptor aggregation or cross-linking with multivalent antigen or
      other cross-linking agents. However, in addition to receptor up-regulation,
      recent studies have shown that monomeric IgE can induce survival and other
      activation events including increased histamine content, degranulation,
      leukotriene release, receptor internalization, adhesion, migration and DNA
      synthesis. Various IgE molecules exhibit a vast spectrum of heterogeneity: the
      highly cytokinergic (HC) group of IgEs at an extreme end of the spectrum can
      induce survival and other activation events very efficiently, whereas poorly
      cytokinergic (PC) IgEs at the other end can do so less efficiently. All the IgEs
      tested appear to be capable of inducing receptor aggregation with HC IgEs having
      a higher capacity to do so than PC IgEs. HC IgEs can promote the production and
      secretion of various cytokines including the one(s) that can sustain survival in
      an autocrine and paracrine mechanism. Consistent with receptor aggregation
      induced by monomeric IgE, other means of receptor aggregation, e.g. IgE+antigen
      and IgE+anti-IgE, can also induce survival and other events in unique ranges of
      stimulation intensity.

PMID- 16605131
TI  - RabGEF1, a negative regulator of Ras signalling, mast cell activation and skin
      inflammation.
AB  - Mast cell activation induced by the aggregation of FcepsilonRI with IgE and
      antigen is mediated through the activation of multiple protein kinase cascades.
      This process induces mast cells to undergo degranulation, to synthesize and
      release lipid mediators, and to secrete multiple cytokines, chemokines and growth
      factors. We found that RabGEF1 (Rabex-5) binds to Ras and negatively regulates
      Ras activation and downstream effector pathways during FcepsilonRI-dependent
      mouse mast cell activation. Mast cells derived from RabGEF1-deficient mice
      exhibit significantly enhanced levels of degranulation, release of lipid
      mediators and secretion of cytokines in response to FcepsilonRI aggregation.
      RabGEF1 knockout mice have increased perinatal mortality and the mice that do
      survive develop severe skin inflammation and increased numbers of mast cells in
      the dermis, some of which exhibit morphological evidence of degranulation. These
      mice also show elevated concentrations of serum histamine and IgE. Thus, RabGEF1
      is a negative regulator of Ras signalling and FcepsilonRI-dependent mast cell
      activation in vitro, and a lack of RabGEF1 results in the development of elevated
      numbers of mast cells in the skin and severe skin inflammation in vivo.

PMID- 16605132
TI  - Role of CC chemokines and their receptors in multiple aspects of mast cell
      biology: comparative protein profiling of FcepsilonRI- and/or CCR1-engaged mast
      cells using protein chip technology.
AB  - Apart from the FcepsilonRI-mediated mechanism, mast cells are activated by
      chemokines. Evidence has accumulated indicating that there is cross-talk between
      the FcepsilonRI-mediated signalling pathway and CC chemokine receptor (CCR)
      mediated signalling pathways in mast cells. We have found that costimulation with
      IgE/antigen and CC chemokine ligand 3 (CCL3) enhances degranulation but inhibits
      chemotaxis of rat basophilic leukaemia (RBL)-2H3 cells expressing human CCR1 (RBL
      CCR1 cells). We hypothesize that this signalling cross-talk in mast cells may
      play important roles in the orchestration and focusing of the allergic response.
      In this study, we have sought information about global protein networks either
      enhanced or inhibited following cross-talk between the FcepsilonRI-mediated and
      CCR-mediated signalling pathways in mast cells. We believe this information may
      be useful for providing an understanding of mast cell function and in the
      establishment of new anti-inflammatory drugs for allergic diseases. Proteomics is
      a promising tool for studying protein profiles within biological samples and
      facilitates an understanding of the complex responses of an organism to a
      stimulus. Here, we show comparative data of protein profiles derived from
      FcepsilonRI-engaged and/or CCR1-engaged RBL-CCR1 cells using protein chip array
      technology, a proteomic technology. We also discuss our view of the role of CC
      chemokines and CCRs in regulating multiple aspects of mast cell biology.

PMID- 16605133
TI  - The role of phosphoinositide-3-kinase in mast cell homing to the gastrointestinal
      tract.
AB  - Phosphoinositide-3-kinases (PI3Ks) are a family of lipid kinases essential in a
      variety of physiological reactions. A series of gene-targeted mice lacking
      different PI3Ks and related molecules has enabled us to understand their in vivo
      roles, particularly those of class IA members. Studies on knockout mice lacking
      class IA PI3Ks and knock-in mice expressing mutant forms of enzymes have revealed
      the importance of this class of PI3Ks in mast cell development in the
      gastrointestinal tract. Here we studied the role of the p85a regulatory subunit,
      the most abundantly expressed regulatory subunit of class IA PI3Ks, using p85a
      knockout mice. Development of mast cells in the gastrointestinal tract but not in
      the skin was severely impaired in mice lacking the p85a regulatory subunit. Stem
      cell factor (SCF)-mediated signalling functions including proliferative response
      and chemotactic activities were both impaired in p85a knockout mast cells, likely
      due to the mast cell deficiency. Mastocytosis upon Strongyloides veneZuelensis
      infection was also impaired in p85alpha knockout mice. Reconstitution with Th2
      conditioned but not untreated bone marrow-derived mast cells (BMMCs) restored
      anti-bacterial immunity, indicating the importance of Th2 response in addition to
      the recruitment of mast cells in the control of nematode infection.

PMID- 16605134
TI  - The mast cell and the cysteinyl leukotrienes.
AB  - The mast cell has been a fundamental focus for nearly half a century in the
      effort to understand the biology of the cysteinyl leukotrienes (cysLTs). My
      initial interest in the cysLTs, once termed the slow reacting substance of
      anaphylaxis (SRS-A), was based on the findings of others that this activity was
      elaborated by lung tissue and constricted bronchial smooth muscle in the presence
      of an antihistamine. We now know that leukotriene C4 (LTC4) is formed when
      arachidonic acid is cleaved from membrane phospholipids, and metabolized to an
      epoxide intermediate, LTA4 that in turn is conjugated to reduced glutathione by
      an integral membrane protein, LTC4 synthase. The LTC4 is exported in an energy
      dependent step and subjected to extracellular cleavage of the glutamic acid and
      then the glycine to provide LTD4 and LTE4, respectively. Mice with targeted
      disruption of the LTC4S gene are partially protected against plasma leakage
      elicited in the ear by adaptive immune mast cell activation or in the peritoneal
      cavity by microbial carbohydrate stimulation of the macrophages. Such mice are
      also partially protected against pulmonary fibrosis after intratracheal
      administration of bleomycin. A strain with targeted disruption of the CysLT1
      receptor gene is protected against the pathobiological insults that augment
      microvascular permeability, whereas a strain with targeted disruption of the
      CysLT2 receptor gene is protected against pulmonary fibrosis. Thus, the
      expression of these receptors on endothelium, smooth muscle and cells of the
      haematopoietic lineage such as mast cells, macrophages, and granulocytes extends
      the possible role of this lipid mediator pathway to both acute and chronic
      inflammation.

PMID- 16605135
TI  - Regulation of gene expression in mast cells: micro-rNA expression and chromatin
      structural analysis of cytokine genes.
AB  - Despite deriving from two different compartments of the immune system (myeloid
      and lymphoid respectively), Th2 cells and mast cells produce the same panel of
      cytokines, interleukin (IL)4, IL5 and IL13. We have compared the chromatin
      structure of the RAD50/IL13/IL4 locus in Th2 cells and mast cells. Th2 and mast
      cells display strong overlap in their patterns of DNase I hypersensitivity
      throughout this locus, except that the first intron of the IL13 gene (MCHS) is
      DNase I hypersensitive only in mast cells and the conserved non-coding sequence
      (CNS)-1 in the IL4/IL13 intergenic region is DNase I hypersensitive only in Th2
      cells (explaining why cytokine expression is impaired in Th2 cells but not in
      mast cells of CNS-1-deleted mice). We have also examined the role of micro-RNAs
      (miRNAs) in the development and activation of mast cells and T cells. miRNAs are
      21- to 25-nucleotide small RNAs that regulate gene expression
      posttranscriptionally by targeting protein-coding mRNAs. Using oligonucleotide
      arrays to analyse miRNA expression in murine T cells and mast cells, we have
      identified distinctive cell type-specific patterns of miRNA expression as well as
      changes related to differentiation and cell activation. We are studying the
      biological functions of selected miRNAs.

PMID- 16605136
TI  - The involvement of Bcl-2 in mast cell apoptosis.
AB  - Apoptosis or programmed cell death plays an important role in a wide variety of
      physiological processes. Apoptosis is regulated by proteins of the Bcl-2 family
      consisting of both anti-apoptotic and pro-apoptotic factors. The direct
      involvement of the Bcl-2 protein family in the process of mast cell apoptosis has
      not been clarified. We have used a single-chain antibody (scFv) raised against
      Bcl-2 derived from human phage-display antibody library. The addition of TAT
      sequence, which is responsible for translocation through the membrane, endows the
      anti-Bcl-2-scFv with the ability to penetrate living cells. The association of
      anti-Bcl-2-scFv-TAT with intracellular Bcl-2 leads to neutralization of Bcl-2 and
      eradication of its anti-apoptotic activity in two types of mast cells and in a
      human breast cancer cell line. Moreover, we found by mass spectrometry and co
      immunoprecipitation assay that heat shock protein 90b (Hsp90b) forms a complex
      with Bcl-2 in mast cells. Thus, understanding the network of interactions between
      Bcl-2 and non-Bcl-2 family members might help in development of more specific
      drugs and cancer therapy.

PMID- 16605137
TI  - Mast cells in autoantibody responses and arthritis.
AB  - A pathogenic role for autoantibodies, immune complexes and mast cells has long
      been hypothesized in rheumatoid arthritis (RA). Recent studies demonstrating
      novel RA-associated autoantibodies and the efficacy of B cell-directed therapy
      have led to a renewed interest in the role of humoral immunity in RA. Mouse
      models of arthritis have provided further support for a direct pathogenic role of
      autoantibodies in the development of synovial inflammation. Interestingly, in
      antibody-mediated K/BxN serum transfer arthritis, mast cells have now been
      identified as a critical cellular mediator of autoantibody-driven joint
      inflammation. Here, we focus on the role of autoantibodies and mast cells in
      murine and human inflammatory arthritis.

PMID- 16605138
TI  - MASTering the immune response: mast cells in autoimmunity.
AB  - Mast cells are established participants in allergic disease and in protection
      against extracellular parasites. Recently, it has become apparent that mast cells
      exert many profound effects on a variety of both innate and adaptive immune
      responses. Using mast cell-deficient WBB6F1/J-kitW/kitWv (W/Wv) mice, we have
      demonstrated that mast cells are critical for severe disease in a murine model of
      multiple sclerosis, experimental allergic encephalomyelitis (EAE). Reconstitution
      of the mast cell population in the periphery, but not the CNS, restores EAE
      severity. Mast cells exert their effects at both the inductive and effector
      phases of disease. EAE is mediated by autoreactive T cells that enter the CNS and
      initiate inflammatory responses, leading to demyelination within the spinal cord
      and brain. Although there are no intrinsic defects in W/Wv-derived T cells, both
      CD4+ and CD8+ autoreactive T cell responses are attenuated during early disease
      in W/Wv mice. Thus mast cells are essential for the optimal priming of
      autoreactive T cells. The entry of encephalitogenic T cells into the CNS is
      compromised in these mice as well. The effects on early T cell responses are due,
      in part, to the reduced percentage of activated dendritic cells in the lymph
      nodes of W/Wv mice after disease induction compared with wild-type mice. The
      finding that mast cells can alter T cell responses in EAE has much broader
      implications for understanding the impact of these cells on all T cell-mediated
      responses.

PMID- 16605139
TI  - Mastocytosis.
AB  - Systemic mast cell disorders in most instances appear to be clonal disorders of
      the mast cell and its progenitor. Symptoms result from a pathological release of
      mast cell mediators and a destructive mast cell infiltration. Cutaneous
      mastocytosis is most frequently seen in children and may regress. Systemic
      mastocytosis (SM) is a persistent disease. A somatic c-kit mutation at codon 816
      is often detectable in haematopoietic cells. The clinical course of mastocytosis
      is variable, ranging from indolent to aggressive. Five categories of disease are
      recognized: Indolent SM, aggressive SM, SM with associated clonal haematological
      non-mast cell-lineage disease (AHNMD) and mast cell leukaemia (MCL). In SM-AHNMD,
      additional genetic abnormalities have been reported. Patients with cutaneous or
      indolent systemic disease are treated symptomatically. Patients with aggressive
      disease are candidates for cytoreductive therapy. The use of 'Kit-targeting'
      tyrosine kinase inhibitors are best selected following a mutational analysis of c
      kit. For instance, the D816V mutation appears to be associated with relative
      resistance against imatinib. However, imatinib has been used with success in
      patients with SM-hypereosinophilic syndrome (HES) and the FIPL1/PDGFRA fusion
      gene and in a patient with mastocytosis with a mutation outside of codon 816. The
      value of bone marrow transplantation remains under investigation.

PMID- 16605140
TI  - Nurses fearful of 'right-to-die' law.

PMID- 16605142
TI  - Boosting the image.

PMID- 16605143
TI  - Everybody's business. Interview by Emma Vere-Jones.

PMID- 16605144
TI  - Implementing the role of the community matron.
AB  - About 17.5 million people in the UK are living with a long-term condition. Part
      of the government strategy to improve outcomes for these people was to introduce
      the role of the community matron. This article builds on previous research by
      examining the community matron role across nine PCTs.

PMID- 16605145
TI  - Removal of chest drains.

PMID- 16605146
TI  - The diagnosis of brainstem death and its implications.
AB  - The concept of brainstem death is relatively new and has been developed in
      response to advances in medical treatment such as mechanical ventilation. The
      idea that it is the same as death of the whole person has been tested in medical
      research and legally, which has provided evidence to support the withdrawal of
      advanced medical treatment and for discussion of organ donation.

PMID- 16605147
TI  - Acute epiglottitis.

PMID- 16605148
TI  - Auditing possible side-effects of atypical antipsychotics.
AB  - This article describes how a tool for auditing the side-effects of atypical
      antipsychotic medication was developed. This was then used to audit case notes
      revealing that care practices were towards the worst practice end of the
      continuum. This article considers the wider implications of this for care and
      education.

PMID- 16605149
TI  - Nystatin.

PMID- 16605150
TI  - Exploring staff nurses' views on professional development.
AB  - AIM: The aim of this study is to explore senior staff nurses' experiences of
      continuing professional development. METHOD: A hermeneutic phenomenological
      methodology was used with a purposive sample of five participants. RESULTS: Four
      key themes were identified: the experience is about being opportunistic; the
      experience is about keeping up to date with ongoing advances in nursing practice;
      the experience is about experiential learning and meeting the demands of the
      informant's current role. CONCLUSION: CPD enabled the nurses who took part in
      this study to keep up to date with nursing practice. It also illustrates that
      engaging with this system of skills enhancement helps to reduce work-related
      stress among nurses, thereby providing further opportunities to enhance
      confidence and competence as well as developing a workforce that is 'fit for
      practice' and 'fit for purpose'.

PMID- 16605151
TI  - Nurse-led triage in general practice.

PMID- 16605152
TI  - Chlamydia screening: making a case for including men.

PMID- 16605153
TI  - Diagnosis and management of lymphoedema.

PMID- 16605154
TI  - What makes the perfect mentor?

PMID- 16605155
TI  - Caring for young adults with dementia. Interview by Victoria Hoban.

PMID- 16605156
TI  - Mouse models to study the pathogenesis and control of bovine mastitis. A review.
AB  - Mastitis is a major infectious disease affecting high yielding cows in dairy
      herds. Because of its economic impact and due to the animal welfare policy, the
      pathogenesis of this intramammary infection was studied extensively over the past
      50 years. Still, the costs associated with the use of dairy cows for mastitis
      research constitute a major drawback. As an alternative, a mouse model of
      experimentally induced mastitis was developed some decades ago. This model has
      been increasingly used as it appears to be very suited for studying ruminant
      mastitis due to similarities between mice and cows. The various techniques for
      inducing mastitis in mice as well as the different pathogens and initial inoculum
      doses used are also compared in this review. Moreover, recent findings concerning
      the administration of antimicrobial and immunomodulatory agents are discussed. In
      addition, information is provided on the most novel approaches for the study of
      mastitis including the use of mutant pathogen strains and transgenic mice.

PMID- 16605157
TI  - Frequency-specific electric response audiometry (ERA) and its clinical
      application in the diagnosis of hearing defects in the dog.
AB  - Reference values were established for frequency-specific electric response
      audiometry (ERA) in dogs on the basis of the results of ERA examinations of 200
      animals with normal hearing. Air-conducting acoustic tubes with foam stoppers
      were used in the determination of the following: the latencies of waves I, III
      and V; interpeak latencies (IPL) I-III, III-V and I-V; amplitudes I and V; and
      the amplitude difference I-V. A frequency-specific stimulus (tone pip) was used
      for frequency-specific examination (1 to 4 kHz) over the entire frequency range
      indicated. These reference values were then used for the clinical examination of
      50 dogs with hearing defects. A frequency-specific ERA was conducted and the
      results evaluated. These findings made it possible to draw objective conclusions
      about the degree, type and site of the hearing defects. Frequency-specific
      electric response audiometry was shown to be an important diagnostic tool for the
      detection of partial high- and low-frequency hearing loss and for the
      characterisation of hearing defects of otological, otoneurological and
      neurological origin.

PMID- 16605158
TI  - Veterinary dairy herd health management in Europe: constraints and perspectives.
AB  - The nature of veterinary work in dairy health management in Europe has changed
      over the past years and will change even more dramatically in the near future.
      The consumers and the media show increasing concern about animal welfare, safety
      of products of animal origin and traceability of animal products. Farmers in
      Europe have to produce under strict, often expensive and laborious regulations,
      while still commercially competing with farmers outside the EU and not subject to
      the same rules. Veterinarians should adapt their knowledge and skills to the new
      challenges and developments of the dairy sector. Dairy farmers nowadays ask for
      support in areas that go beyond clinical activities: environmental protection,
      welfare, nutrition, grassland management, economics and business management.
      Bovine practitioners should be able to advise in many different areas and
      subjects--that is the challenge to our profession. Veterinary education with
      regards to cattle health management should start with individual animal clinical
      work, which constitutes the basis of herd health advisory programmes. The bovine
      practitioner should then look beyond that and regard the herd as the unit. Each
      diseased cow or group of cows should be detected early enough to avoid financial
      losses or such losses should be prevented altogether by detecting and managing
      risk factors contributing to disease occurrence. Herd health and production
      management programmes represent the first level to optimise dairy farm
      performance. Expansions to that should further be considered, comprising both
      animal health and welfare issues, as well as food safety and public health
      issues. The latter could be addressed by quality risk management programmes
      following the HACCP-principles. Cattle veterinarians should follow recent
      developments and invest in new skills and knowledge in order to maintain their
      usefulness to the modern dairy farmer. Finally we are convinced that the cattle
      practitioner should evolve into this direction, otherwise the veterinarian as we
      know him will miss the train in the next years.

PMID- 16605159
TI  - An outbreak of leptospirosis in seals (Phoca vitulina) in captivity.
AB  - An outbreak of leptospirosis in seals (Phoca vitulina) in captivity is described.
      In a zoo in The Netherlands 5 adult seals died within 12 days. At necropsy all
      animals showed signs of acute septicaemia, consistent with acute leptospirosis.
      Serological examination of one animal was positive for antibodies against
      Leptospira interrogans serovar Icterohaemorrhagiae and the serologically closely
      related serovar Copenhageni. Polymerase chain reaction was positive in one other
      animal. 8 nutria (Myocastor coypus) were examined, serologically, through
      bacteriological culture and PCR. 81,8% (9/11) were serologically positive for
      Leptospira. The seals and nutria were housed in the same water system.

PMID- 16605160
TI  - Evaluation of toxic and genotoxic effects of low-level 137Cs ionising radiation
      on plants.
AB  - The aim of this study was to evaluate the impact of low internal exposure to
      137Cs on L. sativum meristem cells and Tradescantia stamen hair cells. It also
      compared the impact of 137Cs internal and external irradiation of similar level
      on the plant seed germination and root growth. Compared to control, the tested
      internal (0.0007 mGy to 0.7 mGy) and external (0.04 mGy to 5.5 mGy) 137Cs
      ionising radiation doses stimulated the elongation of L. sativum roots by 11% to
      12% and 24% to 33%, respectively. Internal 137Cs exposure (0.0003 mGy to 0.5 mGy)
      for 14 days caused 1.2% to 1.6% of somatic mutations and 19% to 87% of non-viable
      stamen hair in Tradescantia.

PMID- 16605161
TI  - Chemical and radiological profile of the coal ash landfill in Kastel Gomilica.
AB  - The objective of this study was to determine the chemical, radiological and
      leaching properties of slag and ash produced by a thermoelectric unit of a former
      factory Adriavinil and deposited in the area of Kasktel Gomilica near Split,
      Croatia. A total of 33 samples were analysed. The bioavailable fraction of the
      slag and ash was estimated using different leaching tests. The waste material was
      characterized by a high activity of naturally occurring radionuclides 238U, 235U
      and 226Ra and by elevated concentrations of heavy metals. The concentrations of
      most heavy metals were three to four times as high as in the common soil. Uranium
      slag and ash concentration was almost 40 times higher than in control soil. More
      than 37% of the total U could be removed from the slag and ash with the sea
      water.

PMID- 16605162
TI  - Study of plutonium migration and/or accumulation in soil under field and
      laboratory conditions.
AB  - This study investigated the dependence of Pu3+ and Pu4+ vertical distribution on
      the soil characteristics in soddy and forest soil. Soil samples were analysed for
      organic matter and pH. Special columns with contaminated (239Pu) soil surface
      were kept for 326 days under field conditions. The analysis of the contaminated
      soil layers (5 cm each, totalling 20 cm) showed that 81% of 239Pu4+, 44% of
      239Pu3+ and 82% of 239Pu4+, 61% of 239Pu3+ were accumulated in the 0-5 cm layer
      of soddy and forest soil. Sequential extraction of the soddy soil 30 days after
      surface contamination with 239Pu, 137Cs and 90Sr showed the following differences
      in radionuclide distribution: the largest amount of 239Pu (60%) and 137Cs (70%)
      were extracted from the residual fraction while 90Sr in this fraction reached
      only about 10%. This suggests that organic substances and some inorganic
      compounds, which usually are the main components of the residual fraction, affect
      the retention and migration of plutonium in the soil.

PMID- 16605163
TI  - Distribution of hydrogen, oxygen and carbon isotopes in the atmosphere of Croatia
      and Slovenia.
AB  - Monitoring of isotope distribution in the atmosphere included isotopes 2H, 3H and
      18O in precipitation, and 13C and 14C in atmospheric CO2. This paper presents the
      results of atmospheric monitoring over Croatia and Slovenia overt the last few
      years. Monthly precipitations in Zagreb and Ljubljana had been collected since
      1976 and 1981, respectively. Between 2000 and 2003 monitoring also included seven
      stations along the Adriatic coast. Tritium activity in precipitation shows
      seasonal variations that were most pronounced inland (at the continental stations
      Zagreb and Ljubljana) and were the smallest in the south Adriatic (Komiza and
      Dubrovnik). Mean annual tritium activity decreases from the north to the south
      Adriatic coast. Seasonal variations in delta2H and delta18O in precipitation
      follow the temperature variations at the sampling stations. Atmospheric CO2 was
      collected in Zagreb and Plitvice as a composite monthly sample. Both delta14C and
      delta13C showed seasonal variations. The mean annual 14C activities in Zagreb had
      been decreasing after the peak reached in the 1960s, and for the last three years
      the mean 14C activity (delta14C) remained about 30 per thousand.

PMID- 16605164
TI  - Evaluation of cytogenetic damage in nuclear medicine personnel occupationally
      exposed to low-level ionising radiation.
AB  - The aim of this study was to provide data on genetic hazards associated with
      occupational exposure to low doses of ionising radiation in nuclear medicine
      departments. The DNA damage in peripheral blood lymphocytes of medical staff was
      assessed using the chromosome aberration test. Altogether 120 subjects (60
      exposed and 60 controls) participated in the study. The exposed subjects showed
      significantly higher frequencies of chromosome aberrations than controls.
      Significant inter-individual differences in DNA damage within the exposed
      population indicate different genome sensitivity. Age and sex were not
      confounding factors, while smoking increased DNA damage only in control subjects.
      This study suggests that chronic exposure to low doses of ionising radiation in
      nuclear medicine departments causes cytogenetic damage. For this reason, exposed
      medical personnel should minimise radiation exposure wherever possible. Our
      results also point to the significance of biological indicators, which provide
      information about the actual risk for the radiation-exposed individuals.

PMID- 16605165
TI  - Public exposure to 226Ra in drinking water.
AB  - This paper presents a new method for calculating the effective dose of 226Ra
      regularly ingested with drinking water over a long period of time. The method is
      based on the assessment of cumulated 226Ra activity in the fraction retained in
      the whole body at time t (in days) after intake [so called m(t) value]. For
      modelling, simulation, and visualisation of the continuous intake of 226Ra by
      drinking water, we used the Simulink program package integrated with the Matlab.
      The dose assessment was performed for 226Ra activities of 5 mBq L(-1), 50 mBq L(
      1), 1000 mBq L(-1) and 5000 mBq L(-1). The results suggest that 226Ra activities
      above 1000 mBq L(-1) produce effective doses which are below the recommended
      maximum. However, the potential effect of 226Ra activities of this extent is
      still unknown in children.

PMID- 16605167
TI  - Non-ionising radiation human exposure assessment near telecommunication devices
      in Croatia.
AB  - This paper gives an overview of the regulatory acts in non-ionising radiation in
      the world, with a special emphasis on basic guidelines issued by the
      International Commission on Non-Ionizing Radiation Protection (ICNIRP). ICNIRP
      Guidelines are implemented in many countries worldwide. Croatia has also
      implemented them indirectly through the European Recommendation 1999/519/EC. The
      Croatian regulatory acts include the Non-lonising Radiation Protection Act,
      Ordinance on Electromagnetic Fields (EMF) Protection, and the Ordinance on Basic
      Requirements for Devices which produce Optical Radiation and Measures for Optical
      Radiation Protection. Dosimetry and densitometry are compliant with relevant
      international and European standards. The paper presents an example of
      densitometric human exposure assessment in complex indoor exposure conditions. In
      spite of a high number of indoor and outdoor sources and the "worst-case exposure
      assessment", the results are within the limits defined by the Croatian EMF
      Ordinance.

PMID- 16605166
TI  - [Radioactivity monitoring of steel processing in Croatian steel mills and
      foundries].
AB  - The last twenty years have seen a number of cases of radioactive pollution in
      metallurgical industry. Therefore many metal producers have implemented
      systematic monitoring of radioactivity in their production processes, especially
      in steel processing, steel being the most applied construction material with the
      annual world output of over billion tonnes. Learning from the experience of the
      best known steel producers in Europe and the world Croatian steel mills have
      introduced radioactivity surveillance and control systems for radioactive
      elements in steel scrap, semi-finished and finished products. This paper argues
      in favour of radioactivity surveillance and control systems in steel and steel
      castings production in Croatia, and describes current systems and solutions
      available. Since we lack our own standards and regulations to control both
      domestic and imported steel scrap, semi-finished products (crude steel, hot and
      cold rolled strip) and finished products, we need to start implementing
      radioactivity surveillance and control systems in our steel and steel castings
      production applying the current international recommendations and guidelines,
      until we build up our own monitoring system and adopt legislation on the national
      level. This paper gives an overview of the basic types of radioactivity
      surveillance and control systems, the most frequent requirements to be met, as
      well as of the measurement and information flow in their application in steel and
      steel castings production.

PMID- 16605168
TI  - Fluorescence in situ hybridisation in detecting chromosome aberrations caused by
      occupational exposure to ionising radiation.
AB  - For more than two decades, chromosome aberration analysis has been used in
      biomonitoring of occupational and environmental exposure to ionising radiation.
      Chromosome aberration analysis is a method used to detect unstable aberrations in
      the lymphocytes of irradiated personnel. In turn, stable chromosome aberrations
      that arise some time after exposure are detected using the multicolour
      fluorescence in situ hybridisation. This is a technique which dyes each pair of
      chromosomes with different colour. Due to the dynamics of unstable aberration
      formation, chromosome aberration analysis is more suitable for genome damage
      assessment of recent exposures. On the other hand, fluorescence in situ
      hybridisation gives information on chromosome instability caused by long-time
      occupational exposure to ionising radiation. Considering the high cost of
      fluorescence in situ hybridisation and the uncertainty of the result, it should
      be used in biodosimetry only when it is absolutely necessary.

PMID- 16605169
TI  - Ellen R. Grass Lecture: Rapid EEG analysis for intensive care decisions in status
      epilepticus.
AB  - Nonconvulsive status epilepticus in intensive care units (ICUs) is common and
      increases the risk of death. Nonconvulsive status epilepticus treatment delays
      are associated with poor patient outcomes. Continuous EEG or EEG-video monitoring
      is used in ICU settings to diagnose subtle seizures and nonconvulsive status
      epilepticus among at-risk populations including patients with closed head
      injuries and altered consciousness, stroke, subarachnoid hemorrhage, neonates at
      risk for sepsis or hypoxic-ischemic encephalopathy, and children who have
      undergone surgery for congenital heart disease. However expert EEG
      interpretation, currently required for accurate diagnosis, often lags behind the
      real-time recordings by hours or even longer. At most hospitals the numbers of at
      risk patients in intensive care units far exceeds the capacity of the available
      EEG equipment and personnel to perform and interpret EEGs. Seizure-detection
      software, compressed EEG spectral arrays, and near real-time remote EEG
      interpretation have brought us closer to the goal of real-time analysis of EEG
      for intensive care decisions, but even at major tertiary referral centers the
      vast majority of at-risk ICU patients do not undergo EEG monitoring. Additional
      technological advances, innovative use of EEG technologists and ICU personnel,
      and clinical trials of new EEG monitoring technology and associated clinical
      outcomes are needed to achieve the goal of optimal use of EEG data for intensive
      care decisions.

PMID- 16605170
TI  - Basic anatomy and physiology of sleep.
AB  - This paper seeks to give a basic look at the structure and physiology of those
      aspects of the nervous and respiratory systems most involved with the cycles of
      sleep. The brain is examined from the hindbrain (the medulla and the pons) to the
      midbrain up through the forebrain (the diencephalon and the telencephalon). Also
      noted are structures that may have a role in sleep and wake cycles, such as the
      reticular activating system, the red nucleus, basal ganglia, pineal gland, and
      the like. The respiratory system's structure and physiology is discussed in broad
      terms. Some of the other factors involved with the generation of slow wave sleep
      and rapid eye movement sleep are also briefly discussed including
      neurotransmitters, hormones, and circadian rhythms. The origins of some of the
      terms used are provided to help facilitate learning.

PMID- 16605171
TI  - Reflex seizures and reflex epilepsy.
AB  - Reflex seizures are evoked by a specific afferent stimulus or by activity of the
      patient and are divided into those characterized by generalized seizures and
      those principally manifested by focal seizures. Reflex epilepsies are syndromes
      in which all epileptic seizures are precipitated by sensory stimuli. Three
      categories of reflex seizures encountered clinically include pure reflex
      epilepsies, reflex seizures that occur in generalized or focal epilepsy syndromes
      that are also associated with spontaneous seizures, and isolated reflex seizures
      occurring in situations that do not necessarily require a diagnosis of epilepsy.
      Generalized reflex seizures are precipitated by visual light stimulation,
      thinking, and decision making. These seizures usually respond to valproate
      treatment. Numerous triggers can induce focal reflex seizures. The triggers
      include reading, writing, other language functions, startle, somatosensory
      stimulation, proprioception, auditory stimuli, immersion in hot water, eating,
      and vestibular stimulation. The classification and characteristics of reflex
      seizures and epilepsies are described in this review. Findings on EEG and
      advanced neuroimaging in the reflex seizures and epilepsies, treatment and
      preventive options, and animal models and mechanisms are also discussed.

PMID- 16605172
TI  - Do you think you have what it takes to set up a long-term video monitoring unit?
AB  - The single most important factor when setting up a long-term video monitoring
      unit is research. Research all vendors by traveling to other sites and calling
      other facilities. Considerations with equipment include the server, acquisition
      units, review units, cameras, software, and monitors as well as other factors
      including Health Insurance Portability and Accountability Act (HIPAA) compliance.
      Research customer support including both field and telephone support. Involve
      your Clinical Engineering Department in your investigations. Be sure to obtain
      warranty information. Researching placement of the equipment is essential.
      Communication with numerous groups is vital. Administration, engineers, clinical
      engineering, physicians, infection control, environmental services, house
      supervisors, security, and all involved parties should be involved in the
      planning.

PMID- 16605173
TI  - Waveform window #4.

PMID- 16605175
TI  - An ominous flu season.

PMID- 16605174
TI  - End innovators and pioneers: Theda Sannit.

PMID- 16605176
TI  - Street-smart safety management.

PMID- 16605177
TI  - Outdoor air damper use in hot and humid climates.

PMID- 16605178
TI  - A politically incorrect guide to protecting your employees.

PMID- 16605179
TI  - How to buy welding safety equipment.

PMID- 16605180
TI  - A guide to LOTO's eight critical elements.

PMID- 16605181
TI  - Safe excavation work essentials.

PMID- 16605182
TI  - Know your netting.

PMID- 16605183
TI  - After the fall: why fall protection isn't always enough.

PMID- 16605184
TI  - In-house advantages.

PMID- 16605185
TI  - Try this recipe for eye and face compliance.

PMID- 16605186
TI  - Disaster roles and responsibilities for safety managers.

PMID- 16605187
TI  - Confined space entry, Part 2.

PMID- 16605188
TI  - The authors and "authors".

PMID- 16605189
TI  - Early complications following radical surgical treatment of patients with gastric
      adenocarcinoma.

PMID- 16605190
TI  - [Early complications following radical surgical treatment of patients with
      gastric adenocarcinoma].
AB  - BACKGROUND/AIM: Surgical treatment of patients with gastric adenocarcinoma means
      the total excision of a tumor and the pathways of its spreading with the risk of
      operational complications as low as possible. The aim of this study was to
      evaluate the type and frequency of early postoperative complications and
      mortality after a radical surgical treatment of patients with gastric
      adenocarcinoma. METHODS: Complication rates and postoperative mortality were
      studied in 70 consecutive patients in whom a radical surgical procedure,
      gastrectomy (total or subtotal) with D2 lymphadenectomy, was performed. In the
      early postoperative period, the frequencies of general and specific complications
      were detected. The frequencies of complications were compared between the groups
      of patients according to the defined clinical, operative and pathohistological
      paramethers. RESULTS: The overall morbidity and mortality rates were 27.14% and
      5.71%, respectively Pancreatic fistula in five, and pleural effusion in three
      patients were the most frequently registered complications. Three of four deaths
      occured in patients older than 70 years, with the stage III and IV of the
      disease, and in all of them total gastrectomy with splenectomy was performed. A
      statistically significant difference (p < 0.05) in complication rates was found
      between the groups of patients with and without splenectomy and with the tumors >
      5 cm and < or = 5 cm. CONCLUSION: Radical surgical treatment of patients with
      gastric adenocarcinoma might be done with an acceptable morbidity and mortality
      if it is performed by the surgeons with the experience in D2 lymphadenectomy
      technique. A diameter of the tumor > 5 cm, and splenectomy, and/or
      splenopancreatectomy are the most important risk factors for the occurrence of
      complications and modifications of D2 lymphadenectomy technique with limited
      indications for splenic and/or pancreas resection can improve treatment results.
      An individual approach and the appropriate selection of the surgical procedure
      are necessary in patients older than 70 years.

PMID- 16605191
TI  - [Endophthalmitis in war and peace penetrating eye injuries].
AB  - BACKGROUND/AIM: Nowadays, eye injuries are a leading cause of one-eye disease or
      blindness worldwide. The aim of this study was to comparatively analyze the
      frequency of endophthalmitis following war and peace eye injuries. METHODS: All
      the patients went throught the detailed ophthalmologic examinations, prophylactic
      antibiotic treatment, and pars plana vitrectomies (VPP), or other required
      surgical interventions. RESULTS: Inside the period from 1991 to 1998, 647
      patients with eye injuries were hospitalized, out of which 500 with penetrating
      eye injuries. In the period 1999-2004, 611 patients with eye injuries, were
      treated, out of which 297 had penetrating eye injuries. Out of 500 patients with
      war penetrating eye injuries, in 286 of the cases intrabulbar foreign bodies
      (IFB) were detected. The signs of endophthalmitis were observed in 26 eyes (5.2%)
      at admission. Out of totally 297 peace penetrating eye injuries, 196 (66%) were
      IBF. In 25 eyes (8.4%) endophthalmitis was observed. CONCLUSION: In our study,
      the frequency of posttraumatic endophthalmitis following penetrating war eye
      injuries was relatively low, even lower than the frequency of endophthalmitis
      following peace eye injuries.

PMID- 16605192
TI  - Microprocessor-controlled vs. "dump-freezing"platelet and lymphocyte
      cryopreservation: a quantitative and qualitative comparative study.
AB  - BACKGROUND/AIM: Thermodynamical and cryobiological parameters responsible for
      cell damages during cryopreservation (cryoinjuries) have not yet been completely
      explained. Thus, freezing procedures should be revised, exactly optimized to
      obtain an enhanced structural and functional recovery of frozen-thawed cells. The
      aim of this study was to compare microprocessor-controlled (controlled-rate) with
      the compensation of the released fusion heat and "dump-freezing" (uncontrolled
      rate) of the platelet and lymphocyte cryopreservation efficacy. METHODS: Platelet
      quantitative recovery (post-thaw vs. unfrozen cell count), viability (using
      hypotonic shock response--HSR), morphological score (PMS), ultrastructural
      (electron microscopy) properties and expression of different surface antigens
      were investigated. In lymphocyte setting, cell recovery and viability (using
      trypan blue exclusion test) as well as functionality (by plant mitogens) were
      determined. Controlled-rate freezing and uncontrolled-rate cryopreservation were
      combined with 6% (platelets) and 10% (lymphocytes) dimethyl sulfoxide (DMSO).
      RESULTS: Platelet recovery and functionality were superior in the controlled-rate
      system. The majority of surface antigen expression was reduced in both freezing
      groups vs. unfrozen cells, but GP140/CD62p was significantly higher in controlled
      rate vs. uncontrolled-rate setting. Controlled-rate freezing resulted with better
      lymphocyte recovery and viability (trypan blue-negative cell percentage). In
      mitogen-induced lymphocyte proliferative response no significant intergroup
      difference (controlled-rate vs. uncontrolled-rate) were found. CONCLUSION: The
      data obtained in this study showned the dependence of cell response on the
      cryopreservation type. Controlled-rate freezing provided a superior platelet
      quantitative and functional recovery. Lymphocyte recovery and viability were
      better in the controlled-rate group, although only a minor intergroup difference
      for cell proliferative response was obtained.

PMID- 16605193
TI  - [Analysis of the use and adverse effects of non-steroidal anti-inflammatory
      drugs: a pilot study].
AB  - BACKGROUND/AIM: The use and adverse effects of non-steroidal anti-inflammatory
      drugs (NSAIDs) in outpatients with rheumatic diseases has not yet been studied
      enough. The aim of this study was to evaluate the data about the efficacy and
      safety of NSAIDs obtained from the questionnaires submitted to the outpatients
      receiving these drugs. METHODS: The patients who had been prescribed any of
      NSAIDs whithin the period from June to September, 2004 were included in the
      study. The answers obtained from the questionnaires were statistically analyzed
      by means of chi2-test. RESULTS: At the time of the study, 150 patients had been
      prescribed ibuprofen or some other NSAID. Out of the total number of dispensed
      questionnaires (n = 150), only 45 (30%) were shown to be correctly filled-in.
      Their analysis showed that 64.4% of the patients had suffered from rheumatic
      diseases for more than five years, and had regularly used NSAIDs. The average age
      of these patients was about 70 years, and the number of females was double as
      high as that of the males. The most frequently used NSAIDs were diclofenac and
      ibuprofen (46.14%, and 23.24%, respectively). According to the answers given by
      the patients, the most often adverse reactions were gastric complaints such as
      nausea (11.1%), and stomach pain (8.9%). Due to this, the majority of the
      patients (64.4%) used some of the antiulcer drugs, most often ranitidine (31.1%).
      CONCLUSION: The results of this pilot study revealed that among the outpatients
      suffering from rheumatic diseases, the number of females was double as high as
      the number of males, that these patients were of the mean age of 70 years, and
      that their diseases lasted longer than five years. Gastric complains such as
      nausea and gastric pain of mild intensity were the most often adverse effects of
      NSAIDs reported by our patients. It could be the consequence of the predominant
      use of diclofenac and ibuprofen, NSAIDs with mild to moderate ulcerogenic
      potential, as well as the concomitant use of H2-receptor antagonists.

PMID- 16605194
TI  - Characteristics of decision-making process during prescribing in general
      practice.
AB  - BACKGROUND/AIM: The process of precribing decision-making by general
      practitioners requires numerous consultations in order to obtain maximal effects,
      minimal risks, and cost-effectiveness with the full appreciation of a patient's
      right to choose. The aim of our study was to describe the process of decision
      making by general practitioners who decide on the treatment for an individual
      patient, and to relate the scope and nature of this process to the quality of the
      outcome of the decision. METHODS: The study involved 53 general practitioners who
      worked in the Health Center, Kragujevac at the time of investigation (September
      December 2002.). General practitioners made prescribing decisions, thinking
      aloud, for five patients with urinary tract infections (n = 2), or stomach
      complaints (n = 3). The resulting 265 transcripts were analyzed to determine the
      scope and nature of the decision-making processes. Differences in prescribing
      were related to the case or the practitioners' working experience, and to their
      educational background. RESULTS: Our results showed that the more years of
      practice the practitioners had the less treatments they prescribed, and the less
      additional aspects before prescribing they considered. The doctors with less
      experience, in most of the cases, considered the core aspects, while those with
      more experience more often considered the contextual and habitual aspects.
      Educational background of the general practitioners, and the type of a considered
      disease, had an influence on the decision-making process. The most optimal method
      for decision-making (marked as type F) was mostly used by the practitioners with
      the least experience, while the those with more experience mainly made their
      decisions in the ways considered the least acceptable. The optimal method for
      decision-making process does not necessarily provide the optimal therapy, so the
      least acceptable decision-making might not result in an inappropriate treatment.
      CONCLUSIONS: The observed prescribing decisions were mostly in disagreement with
      the Good Clinical Practice. Our study pointed out the need for the obligatory
      continuation of medical education of general practitioners in decision-making
      process during prescribing.

PMID- 16605195
TI  - [Prognostic significance of sinus deceleration during dobutamine stress
      echocardiography test following acute myocardial infarction].
AB  - BACKGROUND/AIM: Chronotropic incompetence during exercise stress testing after
      acute myocardial infarction is an indicator of ischemia or impaired left
      ventricular function. On the other side, infusion of dobutamine leads to a
      typical dose-dependent increase in heart rate. The aim of this study was to
      evaluate of paradoxical sinus deceleration during dobutamine stress
      echocardiography (DSE), as the sign of ischemia and impaired left ventricular
      function, or the consequence of infarction localization, and the estimation of
      prognostic significance after acute myocardial infarction. METHODS: Our
      investigation comprised 81 patients hospitalized because of the acute myocardial
      infarction, and all of them had uncomplicated infarction. Fifty five patients
      were treated with thrombolytic therapy (67.9%); 53 patients (65.4%) had anterior
      myocardial infarction, and 28 patients (34.6%) had inferoposterior localization
      of myocardial infarction. After 10-12 days all of them underwent dobutamine
      stress echocardiography examination. During the next 3-6 months, the patients
      underwent coronary angiography. The average follow-up period was 36 +/- 22
      months. RESULTS: A decrease in heart rate occurred at the dobutamine doses
      increasing from 15-40mcg/kg/min in 9 (11.1%) of the patients, in 1 patient with
      an anterior localization and in 8 patients with an inferoposterior localization.
      The decrease was sudden in 4 (44.4%), and gradual in 5 (55.6%) of the patients.
      In 3 patients (33.3%) junction rhythm was developed, and in 2 patients (22.2%) AV
      block II-III. Only in 2 of them, there was a worsening of regional function
      during a high dose dobutamine infusion, but 7 of them showed an improvement
      during a low dose. In 7 (77.8%) of the patients there was a simultaneous decrease
      in blood pressure. Coronary angiographic examination showed that in 4 (44.4%) of
      the patients there was a significant coronary artery disease and they underwent
      the revascularisation procedure. During the follow up period, there was not any
      significant arrhythmic disorder in that group of the patients or repeated
      hospitalization because of postinfarction angina, re-infarction, or heart
      failure. CONCLUSION: We could conclude that paradoxical sinus deceleration is not
      only an indicator of a significant coronary artery disease and "bad left
      ventricle". It also may occur as a consequence of vasodepressor reflex (Bezold
      Jarisch), even after acute myocardial infarction, withont influencing a long-term
      prognosis.

PMID- 16605196
TI  - [Impact of various luting cements on the fixed dentures bonding strength].
AB  - BACKGROUND/AIM: Various luting cements are used to fix dental crowns to prepared
      teeth, and should provide an adhesive bond to the tooth structure giving reliable
      retention. The aim of this study was to establish in vitro which type of the
      tested luting cement provided the strongest adhesive bond of the prepared teeth
      to the fixed denture. METHODS: Testing was carried out on the sample of 100
      intact human premolars extracted for orthodontic reasons. The preparation of the
      teeth was performed by a heavy-duty machine. The surfaces of the prepared teeth
      were mathematically calculated. Dental crowns from the Nickel-Chromium-Molybenum
      (Ni-Cr-Mo) alloy were made in a standard fashion, and fixed to prepared teeth
      (two samples of each group) with 5 different types of luting cements. The
      strength of force applyed to separate the cast crowns from the prepared teeth was
      measured by an electronic dynamometer, after 7 days. RESULTS: The obtained
      results revealed the connection between the type of luting cement and the values
      of retention power. The best adhesive bond under the constant convergence angle
      of the prepared teeth was provided by the resin cement. CONCLUSION: When choosing
      a luting cement for fixing dental crowns to prepared teeth, the advantage should
      be given to the resin cement in case the glassionomers are not available.

PMID- 16605197
TI  - [Distraction osteogenesis in the treatment of facial and mandibular deformities].

PMID- 16605198
TI  - [Intracranial menigioma manifested after delivery in a patient with Hodgkin's
      disease].
AB  - BACKGROUND: Intracranial meningioma is rerely reported in the patients treated
      for Hodgkin's disease (HD), known to mainly occur in the area of radiation
      therapy. CASE REPORT: A 26-year-old woman with HD, and intracranial meningioma
      following the delivery, was presented. As we knew, a similar case had not been
      reported in the literature before. Three years prior the surgery for intracranial
      tumor, the patient had been started to be treated for HD of neoplasm stage I (NS
      I) type, by the use of the standard (bleomycin, etoposide, doxorubicin,
      cyclophosphamide, vincristine, procarbazine, prednisone) BEA-COPP protocol. The
      remission of HD, achieved after 7 cycles, persisted over a 27-month-period up to
      the delivery. Within this period, the patient was without neurologic disorder,
      but with the obvious psychotic behavior, for which the patient was treated with
      haloperidol. Two days following the normal delivery, during the acute disorder of
      the consciousness, intracranial tumor was found. A complete bilateral meningioma
      (11.7 x 8.3 x 8.1 cm) of the frontal parietal zone was removed. CONCLUSION: there
      were no reliable signs of the use of an intensive hemotherapy in the reported
      case (alkylating cytostatics and topoisomerases inhibitors) which might have
      caused the proliferation of a benign solid tumor. The pregnancy was supposed to
      be the possible second risk factor for causing the growth of a meningioma. On the
      basis of the significant psychic disorders before the pregnancy, as well as upon
      the size of the operated on tumor, we concluded that the occurrence of
      intracranial meningioma could be regarded the parallel neoplastic disease or the
      second primary tumor.

PMID- 16605199
TI  - [Cervical lymphodenopathy--a single presentation of sarcoidosis?].
AB  - BACKGROUND: Sarcoidosis is a chronic inflammatory disease, commonly found in
      lungs and hilar lymph nodes, but multiple organs could be involved. The diagnosis
      is based on specific pathohistology which should be always combined with
      clinical, radiological and laboratory findings. CASE REPORT: A patient initially
      presented with pneumonia, and treated with antibiotics, but with the general
      symptoms that persisted despite radiological resolution of lung infiltration was
      reported. The further diagnostic procedures revealed the presence of sarcoid
      granulomas in cervical lymph nodes. The peripheral lymph nodes are often affected
      in the early course of the disease, but it is difficult to distinguish if the
      illness is a sarcoid reaction to lung infection or a acute onset of sarcoidosis.
      CONCLUSION: The detection of sarcoid granulomas in cervical lymph nodes should be
      precisely analyzed for the presence of sarcoidal changes in other tissues,
      primarily in the lungs tissue. Early diagnosis of lung sarcoidosis is
      significant, especially in the light of the fact that the latest studies point
      out that the prednisone therapy, started immediately after the diagnosis has been
      made, renders positive effects also in asympthomatic patients in II and III phase
      of the disease.

PMID- 16605200
TI  - [Association of Helicobacter pylori infection with nodular antritis and
      follicular gastritis].
AB  - INTRODUCTION: Helicobacter pylori (H. pylori) infection is known to be the must
      common cause of chronic gastritis having some endoscopic and pathologic
      characteristies as determinated by the Sydney System for Gastritis
      Classification. The aim of our case report was to point out the relationship
      between an endoscopic finding of nodular antritis and the presence of H. pylori
      infection and active chronic gastritis. CASE REPORT: Our patient underwent upper
      gastrointestinal endoscopy for dyspeptic complaints and was diagnosed as having
      nodular antritis, but also underwent urease test and hystopathologic examination
      of antral mucosa, to determine the presence and density of H. pylori infection
      and the presence and severity of gastritis. After a course of anti H. pylori
      treatment, dyspepsia improved and new biopsy specimens obtained two months and
      six months afterwards revealed no pathological findings. CONCLUSION: The case
      report supported the association of H. pylori infection of lymphoid follicles
      with nodular gastric mucosis.

PMID- 16605201
TI  - [War and peace. Part 2--Peace: peace and humanitarian organizations and Nobel
      Peace Prize].

PMID- 16605202
TI  - [Cytokines and rheumatoid arthritis].

PMID- 16605203
TI  - Clearing up the confusion with Healthy Kids Dental.

PMID- 16605204
TI  - Who owns patient records in a professional corporation?

PMID- 16605205
TI  - How to hire an office manager.

PMID- 16605206
TI  - Creating your referral policy.

PMID- 16605207
TI  - Why the difference in which benefits carriers cover?

PMID- 16605208
TI  - Oral pathology quiz #16: radiolucent lesion in the anterior maxilla.

PMID- 16605209
TI  - Ask yourself: is your practice profitable enough?

PMID- 16605210
TI  - Dental PAC: preventive care for your practice.

PMID- 16605211
TI  - Bisphosphonates: a potential threat to your patients.

PMID- 16605213
TI  - Living out a dental mission.

PMID- 16605212
TI  - Health literacy: an introduction to the literature.
AB  - Adult literacy is inextricably linked with adults' understanding of educational
      and informational materials concerning their health. Approximately 90 million
      American adults are functionally illiterate or have only marginal reading skills.
      This article describe the impact of poor literacy skills on patient health and
      the scope of the challenges to health literacy. The author also describes simple
      steps which dentists can undertake to identify patients with poor literacy skills
      and methods which may help improve educational programs for those patients.

PMID- 16605215
TI  - Advocacy.

PMID- 16605214
TI  - Bottled water: don't sweat it.

PMID- 16605216
TI  - Interview with Richard J. Umbdenstock, CHE, executive vice president, Providence
      Health & Services. Interview by Kyle L Grazier.

PMID- 16605217
TI  - Paying for efficiency.

PMID- 16605218
TI  - Business knowledge and skills.

PMID- 16605219
TI  - Do not go gentle: intractable value differences in hospices.
AB  - As hospices have evolved and grown, from small community-based cottage
      institutions to larger and more complex healthcare providers, they have begun to
      acquire staff with characteristics that are significantly different from those of
      their founding members. Because the timeline of the modern hospice movement is so
      short, many still have founding members at work, and institutions find themselves
      employing people with diverse aspirations and motivations. Such value differences
      would normally be a sufficient basis for conflict in most organizations. In the
      particular context of hospices, and perhaps other healthcare institutions, such
      conflict often goes underground, as each protagonist tries to live up to its
      image of what is appropriate. This narrative research, based in five New Zealand
      hospices, explores the problem of hidden but unresolved tensions and suggests
      some possible avenues for management involvement.

PMID- 16605220
TI  - The nursing shortage: is it really about image?
AB  - A poor public "image" of the nurse is believed to contribute to nurse shortages.
      We surveyed more than 3,000 college students in science and math courses in a
      seven-county region of California's Central Valley to assess their perceptions of
      a career as a nurse in relation to a career as a physical therapist, a high
      school teacher, or a physician. Students generally had favorable perceptions of
      nursing, with two-thirds agreeing that nursing has good income potential, job
      security, and interesting work. However, nursing lagged behind the other
      occupations in perceptions of independence at work and was more likely to be
      perceived as a "women's" occupation. Our findings suggest that these college
      students have generally gotten the message that nursing is a financially
      rewarding and desirable career, although they also perceive nursing to be less
      attractive on some important occupational characteristics such as job
      independence. Unless nursing training capacity expands substantially, the
      projected nurse shortage will occur. With continued aggressive marketing of
      nursing as a career, there is a risk of engendering a backlash from prospective
      students frustrated in their effort to find a slot in a nursing training program.
      Much work remains to be done to alter the image of nursing as a women's
      occupation and to transform the work environment of nurses to make a career in
      nursing more attractive.

PMID- 16605221
TI  - Community orientation, strategic flexibility, and financial performance in
      hospitals.
AB  - The objective of this study was to examine how community orientation and
      strategic flexibility affect accounting measures of financial performance in
      acute care hospitals. This cross-sectional study used organizational data from
      the American Hospital Association, environmental data from the Area Resource
      File, and financial data from the Healthcare Cost Report Information System. We
      tested our hypotheses on 1,779 hospitals using OLS regression models that
      controlled for organizational and environmental factors that might affect
      financial performance. The community orientation of a hospital had a negative
      impact on its short-term financial performance. However, the strategic
      flexibility of a hospital with regard to structure and resources was
      significantly and positively associated with hospital performance. Our findings
      are important to healthcare managers. Specifically, although a community
      orientation is thought to be essential for improving the health of populations,
      the healthcare market may lack clarity concerning the wants and needs of patients
      and payers to such a degree that this orientation does not result in improved
      short-term financial performance. In contrast, when a hospital maintains
      flexibility in its resource allocations and organizational structure, it can meet
      changing needs and uncertainties and thereby enhance financial performance.

PMID- 16605222
TI  - Exploring strategies for reducing hospital errors.
AB  - The purpose of this study is to explore current strategies for reducing errors at
      U.S. hospitals. Reports by the Institute of Medicine highlight concerns about the
      staggering number of medical errors that occur in the U.S. healthcare system.
      These reports have exerted considerable pressure on hospitals to establish
      programs that reduce errors and improve patient safety. A previous research study
      identifies seven critical strategies for reducing hospital errors based on a case
      study of four Chicago-area hospitals. These strategies include (1) partnership
      with stakeholders, (2) reporting errors free of blame, (3) open discussion of
      errors, (4) cultural shift, (5) education and training, (6) statistical analysis
      of data, and (7) system redesign. This article reports the results of our
      nationwide survey of 525 hospitals. We examined the perceptions of healthcare
      quality directors about the importance of these seven patient safety strategies,
      the factors that act as barriers, the level of adoption of these strategies, and
      the benefits resulting from implementation of these strategies. Our results
      indicate that a considerable gap exists between current hospital practices and
      the perceived importance of various approaches to improving patient safety.
      Results of our regression analysis reveal that internal organizational barriers
      are associated with a larger gap between perceived importance and actual
      implementation. Moreover, the regression analysis also reveals that smaller gaps
      are associated with better error outcomes such as reduction in the frequency and
      severity of errors. The findings provide specific directions for enhancing
      patient safety programs at hospitals in the future.

PMID- 16605223
TI  - Improving OB/GYN physician coverage through a redesigned call system.

PMID- 16605225
TI  - Step change.

PMID- 16605226
TI  - The whole story.
AB  - Community matrons have a dual role in the care of people with long-term
      conditions: nursing and co-ordination. The aim is to manage patient care so that
      hospital admissions can be reduced, especially those that result from a crisis.
      Community matrons make detailed assessments of their patients' health and social
      care needs. They work across traditional boundaries, such as secondary care and
      social services. Medication management is part of their remit. Patients are
      visited and reviewed regularly.

PMID- 16605227
TI  - Caring about the costs.
AB  - In his second article on payment by results (PbR), David Newbold considers the
      system's benefits and pitfalls and how nurses and nursing could be affected.

PMID- 16605228
TI  - How to hit the right notes.

PMID- 16605229
TI  - Consumed by an addiction.

PMID- 16605230
TI  - Going cold turkey.

PMID- 16605231
TI  - Nurse prescribing in mental health.
AB  - This article presents a suggested clinical management plan for a community
      psychiatric nurse who is prescribing for older adults with mental health needs.
      The scope of the clinical management plan and the attendant professional and
      legal responsibilities are discussed. An antidepressant medication review is used
      to illustrate mental health prescribing decisions.

PMID- 16605232
TI  - Identifying discharge practice training needs.
AB  - A training needs analysis tool was developed to identify nurses' discharge
      training needs and to improve discharge practice. The tool includes 49 elements
      of discharge practice subdivided into four areas: corporate, operational,
      clinical and nurse-led discharge. The tool was disseminated to 15 wards on two
      hospital sites with assistance from the practice development team. Analysis of
      discharge training is important to assess discharge training needs and to
      identify staff who may assist with training.

PMID- 16605233
TI  - Dysphagia management for progressive neurological conditions.
AB  - This article discusses some of the issues surrounding dysphagia management for
      patients with progressive neurological conditions. It is important that health
      professionals are aware of the available options and that they consider patients'
      wishes to meet their nutritional needs.

PMID- 16605234
TI  - Promoting a healthy diet for older people in the community.
AB  - The promotion of a healthy diet for older people is integral to optimum health
      and effective care. The constituents of a healthy diet are examined and the
      causes and effects of malnutrition explored. This will help nurses to understand
      and undertake effective nutritional assessment for patients in the community.

PMID- 16605235
TI  - Bowel care in spinal patients.

PMID- 16605236
TI  - On course to a new career.

PMID- 16605237
TI  - Buying for results.

PMID- 16605238
TI  - Blooming best.

PMID- 16605239
TI  - Hydration and packing along the folding pathway of SH3 domains by pressure
      dependent NMR.
AB  - The volumetric properties associated with protein folding transitions reflect
      changes in protein packing and hydration of the states that participate in the
      folding reaction. Here, NMR spin relaxation techniques are employed to probe the
      folding-unfolding kinetics of two SH3 domains as a function of pressure so that
      the changes in partial molar volumes along the folding pathway can be measured.
      The two domains fold with rates that differ by approximately 3 orders of
      magnitude, so their folding dynamics must be probed using different NMR
      relaxation experiments. In the case of the drkN SH3 domain that folds via a two
      state mechanism on a time scale of seconds, nitrogen magnetization exchange
      spectroscopy is employed, while for the G48M mutant of the Fyn SH3 domain where
      the folding occurs on the millisecond time scale (three-step reaction),
      relaxation dispersion experiments are utilized. The NMR methodology is extremely
      sensitive to even small changes in equilibrium and rate constants, so reliable
      estimates of partial molar volumes can be obtained using low pressures (1-120
      bar), thus minimizing perturbations to any of the states along the folding
      reaction coordinate. The volumetric data that were obtained are consistent with a
      similar folding mechanism for both SH3 domains, involving early chain compaction
      to states that are at least partially hydrated. This work emphasizes the role of
      NMR spin relaxation in studying dynamic processes over a wide range of time
      scales.

PMID- 16605240
TI  - Inactivation of N-acyl phosphatidylethanolamine phospholipase D reveals multiple
      mechanisms for the biosynthesis of endocannabinoids.
AB  - N-Acyl ethanolamines (NAEs) constitute a large and diverse class of signaling
      lipids that includes the endogenous cannabinoid anandamide. Like other lipid
      transmitters, NAEs are thought to be biosynthesized and degraded on-demand rather
      than being stored in vesicles prior to signaling. The identification of enzymes
      involved in NAE metabolism is therefore imperative to achieve a complete
      understanding of this lipid signaling system and control it for potential
      therapeutic gain. Recently, an N-acyl phosphatidylethanolamine phospholipase D
      (NAPE-PLD) was identified as a candidate enzyme involved in the biosynthesis of
      NAEs. Here, we describe the generation and characterization of mice with a
      targeted disruption in the NAPE-PLD gene [NAPE-PLD(-/-) mice]. Brain tissue from
      NAPE-PLD(-/-) mice showed more than a 5-fold reduction in the calcium-dependent
      conversion of NAPEs to NAEs bearing both saturated and polyunsaturated N-acyl
      chains. However, only the former group of NAEs was decreased in level in NAPE
      PLD(-/-) brains, and these reductions were most dramatic for NAEs bearing very
      long acyl chains (>or=C20). Further studies identified a calcium-independent PLD
      activity in brains from NAPE-PLD(-/-) mice that accepted multiple NAPEs as
      substrates, including the anandamide precursor C20:4 NAPE. The illumination of
      distinct enzymatic pathways for the biosynthesis of long chain saturated and
      polyunsaturated NAEs suggests a strategy to control the activity of specific
      subsets of these lipids without globally affecting the function of the NAE family
      as a whole.

PMID- 16605241
TI  - Inhibition of amyloid fibril formation and cytotoxicity by hydroxyindole
      derivatives.
AB  - Gaining insight into the mechanism of amyloid fibril formation, the hallmark of
      multiple degenerative syndromes of unrelated origin, and exploring novel
      directions of inhibition are crucial for preventing disease development. Specific
      interactions between aromatic moieties were suggested to have a key role in the
      recognition and self-assembly processes leading to the formation of amyloid
      fibrils by several amyloidogenic polypeptides, including the beta-amyloid
      polypeptide associated with Alzheimer's disease. Our finding of the high-affinity
      molecular recognition and intense amyloidogenic potential of tryptophan
      containing peptide fragments led to the hypothesis that screening for indole
      derivatives might lead to the identification of potential inhibitors of amyloid
      formation. Such inhibitors could mediate specific recognition processes without
      allowing further growth of the well-ordered amyloid chain. Using fluorescence
      spectroscopy, atomic force microscopy, and electron microscopy to screen 29
      indole derivatives, we identified three potent inhibitors: indole-3-carbinol
      (I3C), 3-hydroxyindole (3HI), and 4-hydroxyindole (4HI). The latter, a simple low
      molecular weight aromatic compound, was the most effective, completely abrogating
      not only the formation of aggregated structures by Abeta but also the cytotoxic
      activity of aggregated Abeta toward cultured cells. The results of this study
      provide further experimental support for the paradigm of amyloid inhibition by
      heteroaromatic interaction and point to indole derivatives as a simple molecular
      platform for the development of novel fibrillization inhibitors.

PMID- 16605242
TI  - Fluorophore-assisted light inactivation of calmodulin involves singlet-oxygen
      mediated cross-linking and methionine oxidation.
AB  - Fluorophore-assisted light inactivation (FALI) permits the targeted inactivation
      of tagged proteins and, when used with cell-permeable multiuse affinity probes
      (MAPs), offers important advantages in identifying physiological function,
      because targeted protein inactivation is possible with spatial and temporal
      control. However, reliable applications of FALI, also known as chromophore
      assisted light inactivation (CALI) with fluorescein derivatives, have been
      limited by lack of mechanistic information regarding target protein sensitivity.
      To permit the rational inactivation of targeted proteins, we have identified the
      oxidizing species and the susceptibility of specific amino acids to modification
      using the calcium regulatory protein calmodulin (CaM) that, like many essential
      proteins, regulates signal transduction through the reversible association with a
      large number of target proteins. Following the covalent and rigid attachment of
      4',5'-bis(1,3,2-dithioarsolan-2-yl)fluorescein (FlAsH) to helix A, we have
      identified light-dependent oxidative modifications of endogenous methionines to
      their corresponding methionine sulfoxides. Initial rates of methionine oxidation
      correlate with surface accessibility and are insensitive to the distance between
      the bound fluorophore and individual methionines, which vary between
      approximately 7 and 40 A. In addition, we observed a loss of histidines, as well
      as zero-length cross-linking with binding partners corresponding to the CaM
      binding sites of smooth myosin light chain kinase and ryanodine receptor. Our
      results provide a rationale for proteomic screens using FALI to inhibit the
      function of many signaling proteins, which, like CaM, commonly present
      methionines at binding interfaces.

PMID- 16605243
TI  - Structure and interactions of the helical and U-box domains of CHIP, the C
      terminus of HSP70 interacting protein.
AB  - The heat-shock proteins Hsp70 and Hsp90 play a crucial role in regulating protein
      quality control both by refolding and by preventing the aggregation of misfolded
      proteins. It has recently been shown that Hsp70 and Hsp90 act not only in protein
      refolding but also cooperate with the C terminus of Hsp70 interacting protein
      (CHIP), a multidomain ubiquitin ligase, to mediate the degradation of unfolded
      proteins. We present the crystal structure of the helical linker domain and U-box
      domain of zebrafish CHIP (DrCHIP-HU). The structure of DrCHIP-HU shows a
      symmetric homodimer. The conformation of the helical linker domains and the
      relative positions of the helical and U-box domains differ substantially in
      DrCHIP-HU from those in a recently published structure of an asymmetric dimer of
      mammalian (mouse) CHIP. We used an in vitro ubiquitination assay to identify
      residues, located on two long loops and a central alpha helix of the CHIP U-box
      domain, that are important for interacting with the ubiquitin-conjugating enzyme
      UbcH5b. In addition, we used NMR spectroscopy to define a complementary
      interaction surface located on the N-terminal alpha helix and the L4 and L7 loops
      of UbcH5b. Our results provide insights into conformational variability in the
      domain arrangement of CHIP and into U-box-mediated recruitment of UbcH5b for the
      ubiquitination of Hsp70 and Hsp90 substrates.

PMID- 16605244
TI  - Alpha2A- and alpha2C-adrenergic receptors form homo- and heterodimers: the
      heterodimeric state impairs agonist-promoted GRK phosphorylation and beta
      arrestin recruitment.
AB  - Dimerization of seven transmembrane-spanning receptors diversifies their
      pharmacologic and physiologic properties. The alpha(2)-adrenergic receptor
      (alpha(2)AR) subtypes A and C are both expressed on presynaptic nerves and act to
      inhibit norepinephrine release via negative feedback. However, in vivo and in
      vitro studies examining the roles of the two individual alpha(2A)- and
      alpha(2C)AR subtypes are not readily reconciled. We tested the hypothesis that
      the receptors form homo- and heterodimers and that the alpha(2A)-alpha(2C)
      heterodimer has unique properties. SDS-PAGE of epitope-tagged receptors revealed
      potential oligomers including dimers. BRET of live HEK-293 cells transfected with
      the subtypes fused to Rluc or YFP revealed that both subtypes form dimers and the
      heterodimer. A lower BRET(50) for the alpha(2A)-alpha(2C) heterodimer (0.79 +/-
      0.20) compared to that of the alpha(2A) or alpha(2C) homodimer (2.331 +/- 0.44 or
      3.67 +/- 0.69, respectively) suggests that when both subtypes are expressed,
      there is a greater likelihood that the two receptors will form the heterodimer
      than homodimers. Co-immunoprecipitation studies confirmed homo- and heterodimer
      formation. The presence of the alpha(2C)AR within the heterodimer resulted in a
      marked reduction in the level of GRK2-mediated alpha(2A)AR phosphorylation, which
      was accompanied by a qualitative attenuation of beta-arrestin recruitment.
      Signaling of the alpha(2A)-alpha(2C) heterodimer to the beta-arrestin-dependent
      activation of Akt was decreased compared to that of the alpha(2A)AR homodimer,
      while p44/p42 MAP kinase activation was unaffected. Thus, the alpha(2C)AR alters
      alpha(2A)AR signaling by forming oligomers, and these complexes, which appear to
      be preferred over the homodimers, should be considered a functional signaling
      unit in cells in which both subtypes are expressed.

PMID- 16605245
TI  - Redox thermodynamics of the ferric-ferrous couple of wild-type synechocystis KatG
      and KatG(Y249F).
AB  - Crystal structures and mass spectrometric analyses of catalase-peroxidases
      (KatGs) from different organisms revealed the existence of a peculiar distal Met
      Tyr-Trp cross-link. The adduct appears to be important for the catalase but not
      the peroxidase activity of bifunctional KatG. To examine the effect of the adduct
      on enzyme redox properties and functions, we have determined the thermodynamics
      of ferric reduction for wild-type KatG and KatG(Y249F), whose tyrosine-to
      phenylalanine mutation prevents cross-link formation. At 25 degrees C and pH 7.0,
      the reduction potential of wild-type KatG is found to be -226 +/- 10 mV,
      remarkably lower than the published literature values. The reduction potential of
      KatG(Y249F) is very similar (-222 +/- 10 mV), but variable temperature
      experiments revealed compensatory differences in reduction enthalpies and
      entropies. In both proteins, the oxidized state is enthalpically stabilized over
      the reduced state, but entropy is lost on reduction, which is in strong contrast
      to horseradish peroxidase, which also features a much more pronounced enthalpic
      stabilization of the ferriheme. With both proteins, the midpoint potential
      increased linearly with decreasing pH. We discuss whether the observed redox
      thermodynamics reflects the differences in structure and function between
      bifunctional KatG and monofunctional peroxidases.

PMID- 16605246
TI  - Functional role of the "aromatic cage" in human monoamine oxidase B: structures
      and catalytic properties of Tyr435 mutant proteins.
AB  - Current structural results of several flavin-dependent amine oxidizing enzymes
      including human monoamine oxidases A and B (MAO A and MAO B) show aromatic amino
      acid residues oriented approximately perpendicular to the flavin ring, suggesting
      a functional role in catalysis. In the case of human MAO B, two tyrosyl residues
      (Y398 and Y435) are found in the substrate binding site on the re face of the
      covalent flavin ring [Binda et al. (2002) J. Biol. Chem. 277, 23973-23976]. To
      probe the functional significance of this structure, Tyr435 in MAO B was mutated
      with the amino acids Phe, His, Leu, or Trp, the mutant proteins expressed in
      Pichia pastoris, and purified to homogeneity. Each mutant protein contains
      covalent FAD and exhibits a high level of catalytic functionality. No major
      alterations in active site structures are detected on comparison of their
      respective crystal structures with that of WT enzyme. The relative k(cat)/K(m)
      values for each mutant enzyme show Y435 > Y435F = Y435L = Y435H > Y435W. A
      similar behavior is also observed with the membrane-bound forms of MAO A and MAO
      B (MAO A Y444 mutant enzymes are found to be unstable on membrane extraction). p
      Nitrobenzylamine is found to be a poor substrate while p-nitrophenethylamine is
      found to be a good substrate for all WT and mutant forms of MAO B. Analysis of
      these kinetic and structural data suggests the function of the "aromatic cage" in
      MAO to include a steric role in substrate binding and access to the flavin
      coenzyme and to increase the nucleophilicity of the substrate amine moiety. These
      results are consistent with a proposed polar nucleophilic mechanism for catalytic
      amine oxidation.

PMID- 16605247
TI  - Computational and mutational analysis of human glutaredoxin (thioltransferase):
      probing the molecular basis of the low pKa of cysteine 22 and its role in
      catalysis.
AB  - Human glutaredoxin (GRx), also known as thioltransferase, is a 12 kDa thiol
      disulfide oxidoreductase that is highly selective for reduction of glutathione
      containing mixed disulfides. The apparent pK(a) for the active site Cys22 residue
      is approximately 3.5. Previously we observed that the catalytic enhancement by
      glutaredoxin could be ascribed fully to the difference between the pK(a) of its
      Cys22 thiol moiety and the pK(a) of the product thiol, each acting as a leaving
      group in the enzymatic and nonenzymatic reactions, respectively [Srinivasan et
      al. (1997), Biochemistry 36, 3199-3206]. Continuum electrostatic calculations
      suggest that the low pK(a) of Cys22 results primarily from stabilization of the
      thiolate anion by a specific ion-pairing with the positively charged Lys19
      residue, although hydrogen bonding interactions with Thr21 also appear to
      contribute. Variants of Lys19 were considered to further assess the predicted
      role of Lys19 on the pK(a) of Cys22. The variants K19Q and K19L were generated by
      molecular modeling, and the pK(a) value for Cys22 was calculated for each
      variant. For K19Q, the predicted Cys22 pK(a) is 7.3, while the predicted value is
      8.3 for K19L. The effects of the mutations on the interaction energy between the
      adducted glutathionyl moiety and GRx were roughly estimated from the van der
      Waals and electrostatic energies between the glutathionyl moiety and proximal
      protein residues in a mixed disulfide adduct of GRx and glutathione, i.e., the
      GRx-SSG intermediate. The values for the K19 mutants differed by only a small
      amount compared to those for the wild type enzyme intermediate. Together, the
      computational analysis predicted that the mutant enzymes would have markedly
      reduced catalytic rates while retaining the glutathionyl specificity displayed by
      the wild type enzyme. Accordingly, we constructed and characterized the K19L and
      K19Q mutants of two forms of the GRx enzyme. Each of the mutants retained
      glutathionyl specificity as predicted and displayed diminution in activity, but
      the decreases in activity were not to the extent predicted by the theoretical
      calculations. Changes in the respective Cys22-thiol pK(a) values of the mutant
      enzymes, as shown by pH profiles for iodoacetamide inactivation of the respective
      enzymes, clearly revealed that the K19-C22 ion pair cannot fully account for the
      low pK(a) of the Cys22 thiol. Additional contributions to stabilization of the
      Cys22 thiolate are likely donated by Thr21 and the N-terminal partial positive
      charge of the neighboring alpha-helix.

PMID- 16605248
TI  - Oligosaccharide binding in family 8 glycosidases: crystal structures of active
      site mutants of the beta-1,4-xylanase pXyl from Pseudoaltermonas haloplanktis
      TAH3a in complex with substrate and product.
AB  - The structures of inactive mutants D144A and E78Q of the glycoside hydrolase
      family 8 (GH-8) endo-beta-1,4-d-xylanase (pXyl) from the Antarctic bacterium
      Pseudoalteromonas haloplanktis TAH3a in complex with its substrate xylopentaose
      (at 1.95 A resolution) and product xylotriose (at 1.9 A resolution) have been
      determined by X-ray crystallography. A detailed comparative analysis of these
      with the apo-enzyme and with other GH-8 structures indicates an induced fit
      mechanism upon ligand binding whereby a number of conformational changes and, in
      particular, a repositioning of the proton donor into a more catalytically
      competent position occurs. This has also allowed for the description of protein
      ligand interactions in this enzyme and for the demarcation of subsites -3 to +3.
      An in-depth analysis of each of these subsites gives an insight into the
      structure-function relationship of this enzyme and the basis of xylose/glucose
      discrimination in family 8 glycoside hydrolases. Furthermore, the structure of
      the -1/+1 subsite spanning complex reveals that the substrate is distorted from
      its ground state conformation. Indeed, structural analysis and in silico docking
      studies indicate that substrate hydrolysis in GH-8 members is preceded by a
      conformational change, away from the substrate ground-state chair conformation,
      to a pretransition state local minimum (2)S(O) conformation.

PMID- 16605249
TI  - Structural perturbations in the Ala --> Val polymorphism of
      methylenetetrahydrofolate reductase: how binding of folates may protect against
      inactivation.
AB  - In human methylenetetrahydrofolate reductase (MTHFR) the Ala222Val (677C-->T)
      polymorphism encodes a heat-labile gene product that is associated with elevated
      levels of homocysteine and possibly with risk for cardiovascular disease.
      Generation of the equivalent Ala to Val mutation in Escherichia coli MTHFR, which
      is 30% identical to the catalytic domain of the human enzyme, creates a protein
      with enhanced thermolability. In both human and E. coli MTHFR, the A --> V
      mutation increases the rate of dissociation of FAD, and in both enzymes, loss of
      FAD is linked to changes in quaternary structure [Yamada, K., Chen, Z., Rozen,
      R., and Matthews, R. G. (2001) Proc. Natl. Acad. Sci. U.S.A. 98, 14853-14858;
      Guenther, B. D., Sheppard, C. A., Tran, P., Rozen, R., Matthews, R. G., and
      Ludwig, M. L. (1999) Nat. Struct. Biol. 6, 359-365]. Folates have been shown to
      protect both human and bacterial enzymes from loss of FAD. Despite its effect on
      affinity for FAD, the A --> V mutation is located at the bottom of the
      (betaalpha)(8) barrel of the catalytic domain in a position that does not contact
      the bound FAD prosthetic group. Here we report the structures of the Ala177Val
      mutant of E. coli MTHFR and of its complex with the 5,10-dideazafolate analogue,
      LY309887, and suggest mechanisms by which the mutation may perturb FAD binding.
      Helix alpha5, which immediately precedes the loop bearing the mutation, carries
      several residues that interact with FAD, including Asn168, Arg171, and Lys172. In
      the structures of the mutant enzyme this helix is displaced, perturbing protein
      FAD interactions. In the complex with LY309887, the pterin-like ring of the
      analogue stacks against the si face of the flavin and is secured by hydrogen
      bonds to residues Gln183 and Asp120 that adjoin this face. The direct
      interactions of bound folate with the cofactor provide one mechanism for linkage
      between binding of FAD and folate binding that could account in part for the
      protective action of folates. Conformation changes induced by folate binding may
      also suppress dissociation of FAD.

PMID- 16605250
TI  - Structure-function relationships in human glutathione-dependent formaldehyde
      dehydrogenase. Role of Glu-67 and Arg-368 in the catalytic mechanism.
AB  - The active-site zinc in human glutathione-dependent formaldehyde dehydrogenase
      (FDH) undergoes coenzyme-induced displacement and transient coordination to a
      highly conserved glutamate residue (Glu-67) during the catalytic cycle. The role
      of this transient coordination of the active-site zinc to Glu-67 in the FDH
      catalytic cycle and the associated coenzyme interactions were investigated by
      studying enzymes in which Glu-67 and Arg-368 were substituted with Leu.
      Structures of FDH.adenosine 5'-diphosphate ribose (ADP-ribose) and E67L.NAD(H)
      binary complexes were determined. Steady-state kinetics, isotope effects, and
      presteady-state analysis of the E67L enzyme show that Glu-67 is critical for
      capturing the substrates for catalysis. The catalytic efficiency (V/K(m)) of the
      E67L enzyme in reactions involving S-nitrosoglutathione (GSNO), S
      hydroxymethylglutathione (HMGSH) and 12-hydroxydodecanoic acid (12-HDDA) were 25
      000-, 3000-, and 180-fold lower, respectively, than for the wild-type enzyme. The
      large decrease in the efficiency of capturing GSNO and HMGSH by the E67L enzyme
      results mainly because of the impaired binding of these substrates to the mutant
      enzyme. In the case of 12-HDDA, a decrease in the rate of hydride transfer is the
      major factor responsible for the reduction in the efficiency of its capture for
      catalysis by the E67L enzyme. Binding of the coenzyme is not affected by the Glu
      67 substitution. A partial displacement of the active-site zinc in the FDH.ADP
      ribose binary complex indicates that the disruption of the interaction between
      Glu-67 and Arg-368 is involved in the displacement of active-site zinc. Kinetic
      studies with the R368L enzyme show that the predominant role of Arg-368 is in the
      binding of the coenzyme. An isomerization of the ternary complex before hydride
      transfer is detected in the kinetic pathway of HMGSH. Steps involved in the
      binding of the coenzyme to the FDH active site are also discerned from the unique
      conformation of the coenzyme in one of the subunits of the E67L.NAD(H) binary
      complex.

PMID- 16605251
TI  - Inhibitory antibodies to human angiotensin-converting enzyme: fine epitope
      mapping and mechanism of action.
AB  - Angiotensin I-converting enzyme (ACE), a key enzyme in cardiovascular
      pathophysiology, consists of two homologous domains (N and C), each bearing a Zn
      dependent active site. We modeled the 3D-structure of the ACE N-domain using
      known structures of the C-domain of human ACE and the ACE homologue, ACE2, as
      templates. Two monoclonal antibodies (mAb), 3A5 and i2H5, developed against the
      human N-domain of ACE, demonstrated anticatalytic activity. N-domain modeling and
      mutagenesis of 21 amino acid residues allowed us to define the epitopes for these
      mAbs. Their epitopes partially overlap: amino acid residues K407, E403, Y521,
      E522, G523, P524, D529 are present in both epitopes. Mutation of 4 amino acid
      residues within the 3A5 epitope, N203E, R550A, D558L, and K557Q, increased the
      apparent binding of mAb 3A5 with the mutated N-domain 3-fold in plate
      precipitation assay, but abolished the inhibitory potency of this mAb. Moreover,
      mutation D558L dramatically decreased 3A5-induced ACE shedding from the surface
      of CHO cells expressing human somatic ACE. The inhibition of N-domain activity by
      mAbs 3A5 and i2H5 obeys similar kinetics. Both mAbs can bind to the free enzyme
      and enzyme-substrate complex, forming E.mAb and E.S.mAb complexes, respectively;
      however, only complex E.S can form a product. Kinetic analysis indicates that
      both mAbs bind better with the ACE N-domain in the presence of a substrate,
      which, in turn, implies that binding of a substrate causes conformational
      adjustments in the N-domain structure. Independent experiments with ELISA
      demonstrated better binding of mAbs 3A5 and i2H5 in the presence of the inhibitor
      lisinopril as well. This effect can be attributed to better binding of both mAbs
      with the "closed" conformation of ACE, therefore, disturbing the hinge-bending
      movement of the enzyme, which is necessary for catalysis.

PMID- 16605252
TI  - Identification of the binding region of the [2Fe-2S] ferredoxin in stearoyl-acyl
      carrier protein desaturase: insight into the catalytic complex and mechanism of
      action.
AB  - Stearoyl-acyl carrier protein desaturase (Delta9D) catalyzes the O(2) and 2e(-)
      dependent desaturation of stearoyl-acyl carrier protein (18:0-ACP) to yield
      oleoyl-ACP (18:1-ACP). The 2e(-) are provided by essential interactions with
      reduced plant-type [2Fe-2S] ferredoxin (Fd). We have investigated the protein
      protein interface involved in the Fd-Delta9D complex by the use of chemical cross
      linking, site-directed mutagenesis, steady-state kinetic approaches, and
      molecular docking studies. The treatment of the different proteins with 1-ethyl-3
      (3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide revealed that
      carboxylate residues from Fd and lysine residues from Delta9D contribute to cross
      linking. The single substitutions of K60A, K56A, and K230A on Delta9D decreased
      the k(cat)/K(M) for Fd by 4-, 22-, and 2400-fold, respectively, as compared to wt
      Delta9D and a K41A substitution. The double substitution K56A/K60A decreased the
      k(cat)/K(M) for Fd by 250-fold, whereas the triple mutation K56A/K60A/K230A
      decreased the k(cat)/K(M) for Fd by at least 700 000-fold. These results strongly
      implicate the triad of K56, K60, and K230 of Delta9D in the formation of a
      catalytic complex with Fd. Molecular docking studies indicate that electrostatic
      interactions between K56 and K60 and the carboxylate groups on Fd may situate the
      [2Fe-2S] cluster of Fd closer to W62, a surface residue that is structurally
      conserved in both ribonucleotide reductase and mycobacterial putative acyl-ACP
      desaturase DesA2. Owing to the considerably larger effects on catalysis, K230
      appears to have other contributions to catalysis arising from its positioning in
      helix 7 and its close spatial location to the diiron center ligands E229 and
      H232. These results are considered in the light of the presently available models
      for Fd-mediated electron transfer in Delta9D and other protein-protein complexes.

PMID- 16605253
TI  - Temperature-dependent interactions between photoactivated pharaonis
      phoborhodopsin and its transducer.
AB  - Pharaonis phoborhodopsin (ppR, also called pharaonis sensory rhodopsin II, psRII)
      is a receptor for negative phototaxis in Natronomonas pharaonis. In membranes, it
      forms a 2:2 complex with its transducer protein pHtrII, and the association is
      weakened by 2 orders of magnitude in the M intermediate (ppR(M)). Such a change
      is believed to correspond to the transfer of the light signal to pHtrII. A
      previous Fourier transform infrared (FTIR) study observed hydrogen-bonding
      alteration of Asn74 in pHtrII in the M state, suggesting a light-signaling
      pathway from the receptor to the transducer [Furutani, Y., Kamada, K., Sudo, Y.,
      Shimono, K., Kamo, N., and Kandori, H. (2005) Biochemistry 44, 2909-2915]. In
      this paper, we measure temperature dependence of the ppR(M) minus ppR spectra in
      the absence and presence of pHtrII at 250-293 K. Significant temperature
      dependence was observed for the amide-I vibrations of helices only for the
      ppR/pHtrII complex, where the amplitude of amide-I vibrations was reduced at room
      temperature. (13)C-Labeling of ppR or pHtrII revealed that such spectral changes
      of helices originate from ppR and not pHtrII. The hydrogen-bonding alteration of
      Asn74 in pHtrII was temperature-independent, implying that the observed helical
      structural perturbation in ppR takes place in different region. On the other
      hand, temperature-dependent structural changes of helices were diminished for the
      complex of ppR with the G83C and G83F mutants of pHtrII. Gly83 is believed to
      connect the transmembrane helix and cytosolic linker region in a flexible kink
      near the membrane surface of pHtrII, and its replacement by Cys or Phe abolishes
      the photosensory function. The present study provides direct experimental
      evidence that Gly83 plays an important structural role in the activation
      processes of the ppR/pHtrII complex. A molecular mechanism of protein structural
      changes in the ppR/pHtrII complex is discussed on the basis of the present FTIR
      results.

PMID- 16605254
TI  - Structural and functional characterization of the TgDRE multidomain protein, a
      DNA repair enzyme from Toxoplasma gondii.
AB  - The parasite Toxoplasma gondii expresses a 55 kDa protein or TgDRE that belongs
      to a novel family of proteins characterized by the presence of three domains, a
      human splicing factor 45-like motif (SF), a glycine-rich motif (G-patch), and a
      RNA recognition motif (RRM). The two latter domains are mainly known as RNA
      binding domains, and their presence in TgDRE, whose partial DNA repair function
      was demonstrated, suggests that the protein could also be involved in the RNA
      metabolism. In this work, we characterized the structure and function of the
      different domains by using single or multidomain proteins to define their
      putative role. The SF45-like domain has a helical conformation and is involved in
      the oligomerization of the protein. The G-patch domain, mainly unstructured on
      its own as well as in the presence of the SF upstream and RRM downstream domains,
      is able to bind small RNA oligonucleotides. We also report the structure
      determination of the RRM domain from the NMR data. It adopts a classical
      betaalphabetabetaalphabeta topology consisting of a four-stranded beta sheet
      packed against two alpha helices but does not present the key residues for the
      RNA interaction. In contrast, our analysis shows that the RRM of TgDRE is not
      only unable to bind small RNA oligonucleotides but it also shares the protein
      protein interaction characteristics with two unusual RRMs of the U2AF
      heterodimeric splicing factor. The presence of both RNA- and protein-binding
      domains seems to indicate that TgDRE could also be involved in RNA metabolism.

PMID- 16605255
TI  - Escherichia coli Hfq binds A18 and DsrA domain II with similar 2:1 Hfq6/RNA
      stoichiometry using different surface sites.
AB  - Hfq is a RNA-binding protein in Escherichia coli that plays an essential role in
      post-transcriptional regulation of mRNAs by facilitating pairing of noncoding
      RNAs (ncRNAs) to mRNA target sites. Recent work has provided evidence that E.
      coli Hfq has two distinct RNA-binding surfaces. In this study, a comparative
      sequence-structure analysis of hfq genes in bacterial genomes was employed to
      identify conserved residues that may be involved in binding RNA. A covariance of
      residue properties at neighboring positions 12 and 39 and conserved surface
      residues with high propensities at binding sites of RNA-binding proteins
      suggested several sites for Hfq-RNA interactions. On the basis of these
      predictions, eight mutant Hfq proteins were produced and their interactions were
      examined with the 38 nucleotide (nt) domain II of DsrA ncRNA (DsrA(DII)) and
      A(18) by a gel-mobility shift assay, fluorescence anisotropy, and fluorescence
      quenching. Mutations on the proximal surface of Hfq had a small affect on Hfq
      binding to A(18) (<or=2-fold), while the mutations Y25A and K31A on the distal
      surface decreased affinity to A(18) by 100-fold in solution. Mutations F39A and
      R16A on the proximal surface reduced affinity to DsrA(DII) by 6-8-fold, while
      other mutations on the distal or proximal surfaces affected affinity to DsrA(DII)
      by <or=2-fold using the gel-mobility shift assay. The F39A/L12F double mutation
      partially regained the affinity for DsrA(DII) lost by the F39A mutation. The
      latter observation is consistent with the implied importance of an aromatic
      residue at position 12 or 39 suggested by the sequence covariance. Titration
      experiments indicate a 2:1 Hfq(6)/RNA stoichiometry for the strong binding
      complexes of Hfq with either A(18) or DsrA(DII) and suggests that RNA-induced
      dimer formation of Hfq(6) is a common feature of Hfq-RNA interactions.

PMID- 16605256
TI  - Influence of phylogeny on posttranscriptional modification of rRNA in
      thermophilic prokaryotes: the complete modification map of 16S rRNA of Thermus
      thermophilus.
AB  - Posttranscriptional modification in RNA generally serves to fine-tune and
      regulate RNA structure and, in many cases, is relatively conserved and
      phylogenetically distinct. We report the complete modification map for SSU rRNA
      from Thermus thermophilus, determined primarily by HPLC/electrospray ionization
      MS-based methods. Thermus modification levels are significantly lower, and
      structures at the nucleoside level are very different from those of the archaeal
      thermophile Sulfolobus solfataricus growing in the same temperature range [Noon,
      K. R., et al. (1998) J. Bacteriol. 180, 2883-2888]. The Thermus modification map
      is unexpectedly similar to that of Escherichia coli (11 modified sites), with
      which it shares identity in 8 of the 14 modifications. Unlike the heavily
      methylated Sulfolobus SSU RNA, Thermus contains a single ribose-methylated
      residue, N(4),2'-O-dimethylcytidine-1402, suggesting that O-2'-ribose methylation
      in this bacterial thermophile plays a reduced role in thermostabilization
      compared with the thermophilic archaea. Adjacent pseudouridine residues were
      found in the single-stranded 3' tail of Thermus 16S rRNA at residues 1540 and
      1541 (E. coli numbering) in the anti-Shine-Dalgarno mRNA binding sequence. The
      present results provide an example of the potential of LC/MS for extensive
      modification mapping in large RNAs.

PMID- 16605257
TI  - Thermal unfolding of plastocyanin from the mesophilic cyanobacterium
      Synechocystis sp. PCC 6803 and comparison with its thermophilic counterpart from
      Phormidium laminosum.
AB  - The thermal unfolding of plastocyanin from the mesophilic cyanobacterium
      Synechocystis is described herein, and the results are compared with those
      obtained for the homologous thermophilic protein from Phormidium laminosum. The
      thermal unfolding is irreversible under all the conditions that were
      investigated. Plastocyanin from the thermophilic organism, both in the native
      state and in the apoprotein form, proved to be more thermostable than its
      mesophilic counterpart under all experimental conditions. Synechocystis reduced
      plastocyanin has been shown to be more stable than the oxidized species, both
      with respect to the required temperature for protein unfolding and with respect
      to the kinetics of the process. This behavior contrasts with that observed for
      Phormidium plastocyanin, in which the oxidized form is the more stable one. The
      unfolding pH dependence and kinetic studies indicate that around physiological
      pH, the most kinetically stable form is also the one more resistant to
      temperature variations, suggesting a close compromise between function and
      stability. Molecular dynamics simulations suggest that Phormidium and
      Synechocystis plastocyanins follow different unfolding pathways that affect
      different protein areas and which could be responsible for the observed
      dissimilar thermal resistance.

PMID- 16605258
TI  - Presenilin-dependent gamma-secretase on plasma membrane and endosomes is
      functionally distinct.
AB  - The presenilin (PS)/gamma-secretase complex, which contains not only PS but also
      Aph-1, PEN-2, and nicastrin, mediates proteolysis of the transmembrane domain of
      beta-amyloid protein precursor (betaAPP). Intramembrane proteolysis occurs at the
      interface between the membrane and cytosol (epsilon-site) and near the middle of
      the transmembrane domain (gamma-site), generating the betaAPP intracellular
      domain (AICD) and Alzheimer disease-associated Abeta, respectively. Both cleavage
      sites exhibit some diversity. Changes in the precision of gamma-cleavage, which
      potentially results in secretion of pathogenic Abeta42, have been intensively
      studied, while those of epsilon-cleavage have not. Although a number of PS
      associated factors have been identified, it is unclear whether any of them
      physiologically regulate the precision of cleavage by PS/gamma-secretase.
      Moreover, there is currently no clear evidence of whether PS/gamma-secretase
      function differs according to the subcellular site. Here, we show that
      endocytosis affects the precision of PS-dependent epsilon-cleavage in cell
      culture. Relative production of longer AICDepsilon49 increases on the plasma
      membrane, whereas that of shorter AICDepsilon51 increases on endosomes; however,
      this occurs without a concomitant major change in the precision of cleavage at
      gamma-sites. Moreover, very similar changes in the precision of epsilon-cleavage
      are induced by alteration of the pH. Our findings demonstrate that the precision
      of epsilon-cleavage by PS/gamma-secretase changes depending upon the conditions
      and the subcellular location. These results suggest that the precision of
      cleavage by the PS/gamma-secretase complex may be physiologically regulated by
      the subcellular location and conditions.

PMID- 16605259
TI  - Caged vanilloid ligands for activation of TRPV1 receptors by 1- and 2-photon
      excitation.
AB  - Nociceptive neurons in the peripheral nervous system detect noxious stimuli and
      report the information to the central nervous system. Most nociceptive neurons
      express the vanilloid receptor, TRPV1, a nonselective cation channel gated by
      vanilloid ligands such as capsaicin, the pungent essence of chili peppers. Here,
      we report the synthesis and biological application of two caged vanilloids:
      biologically inert precursors that, when photolyzed, release bioactive vanilloid
      ligands. The two caged vanilloids, Nb-VNA and Nv-VNA, are photoreleased with
      quantum efficiency of 0.13 and 0.041, respectively. Under flash photolysis
      conditions, photorelease of Nb-VNA and Nv-VNA is 95% complete in approximately 40
      micros and approximately 125 micros, respectively. Through 1-photon excitation
      with ultraviolet light (360 nm), or 2-photon excitation with red light (720 nm),
      the caged vanilloids can be photoreleased in situ to activate TRPV1 receptors on
      nociceptive neurons. The consequent increase in intracellular free Ca(2+)
      concentration ([Ca(2+)](i)) can be visualized by laser-scanning confocal imaging
      of neurons loaded with the fluorescent Ca(2+) indicator, fluo-3. Stimulation
      results from TRPV1 receptor activation, because the response is blocked by
      capsazepine, a selective TRPV1 antagonist. In Ca(2+)-free extracellular medium,
      photoreleased vanilloid can still elevate [Ca(2+)](i), which suggests that TRPV1
      receptors also reside on endomembranes in neurons and can mediate Ca(2+) release
      from intracellular stores. Notably, whole-cell voltage clamp measurements showed
      that flash photorelease of vanilloid can activate TRPV1 channels in <4 ms at 22
      degrees C. In combination with 1- or 2-photon excitation, caged vanilloids are a
      powerful tool for probing morphologically distinct structures of nociceptive
      sensory neurons with high spatial and temporal precision.

PMID- 16605260
TI  - Dimerization specificity of adult and neonatal chicken skeletal muscle myosin
      heavy chain rods.
AB  - The dimerization specificity of the recombinantly expressed and purified rod
      domain of adult and neonatal chicken myosin heavy chain was analyzed using metal
      chelation chromatography. Our results indicate that full-length adult and
      neonatal rods preferentially formed homodimers when renatured from an equimolar
      mixture of the two isoforms denatured in guanidine hydrochloride. The
      contribution made toward the dimerization specificity by subdomains of the rod
      has been addressed by making a chimeric protein consisting of the subfragment 2
      (S2) region of the adult isoform and the light meromyosin region of the neonatal
      isoform. The proportion of heterodimers formed in exchange experiments between
      the chimera and the neonatal and adult rods rose with increase in the sequence
      homology between the two exchanging proteins. This suggests that multiple regions
      of the rod domain of chicken MyHC including S2 can contribute toward dimerization
      specificity.

PMID- 16605261
TI  - T7 RNA polymerase-induced bending of promoter DNA is coupled to DNA opening.
AB  - To initiate transcription, T7 RNA polymerase (RNAP) forms a specific complex with
      its promoter DNA and melts several base pairs near the initiation site to form an
      open complex. Previous gel electrophoresis studies have indicated that the
      promoter DNA in the initiation complex is bent [Ujvari, A., and Martin, C. T.
      (2000) J. Mol. Biol. 295, 1173-1184]. Here we use fluorescence resonance energy
      transfer (FRET) to investigate the conformation of promoter DNA in the closed and
      open complexes of T7 RNAP. We have used steady state and time-resolved
      fluorescence approaches to measure the FRET efficiency in a doubly dye-labeled
      duplex promoter and in a premelted bubble promoter. Changes in the FRET
      efficiency and hence the DNA end-to-end distance changes are small when the
      duplex promoter forms a complex with T7 RNAP. On the other hand, FRET changes are
      relatively larger when the bubble promoter binds T7 RNAP or when initiating
      nucleotides are added to the duplex promoter-T7 RNAP complex. The shortening of
      DNA end-to-end distances is indicative of DNA bending in the bubble DNA complex
      and in the duplex promoter complex with the initiating nucleotides. Our results
      are consistent with the model in which in the absence of initiating nucleotides
      there is a distribution of closed and open complexes, and the promoter DNA is
      bent slightly by <40 degrees in the closed complex but bent more sharply by 86
      degrees in the open complex. The energetics of DNA bending suggests that a
      significant part of the available free energy from promoter and polymerase
      interactions is utilized in DNA bending and/or untwisting. We propose that
      promoter opening occurs spontaneously upon DNA bending and/or untwisting as free
      energy is gained through interactions of the melted promoter with the T7 RNAP
      active site.

PMID- 16605263
TI  - Activation of individual alphaIIbbeta3 integrin molecules by disruption of
      transmembrane domain interactions in the absence of clustering.
AB  - We used laser tweezers-based force spectroscopy to measure the binding strength
      between fibrinogen molecules covalently bound to latex beads and either wild-type
      alphaIIbbeta3 molecules or alphaIIbbeta3 molecules containing the transmembrane
      domain mutations beta3 G708N or alphaIIb G972N expressed on Chinese hamster ovary
      cells. As we demonstrated previously for alphaIIbbeta3 on agonist-stimulated
      platelets and for purified alphaIIbbeta3 molecules incubated with Mn(2+), two
      regimes of rupture forces were present when wild-type alphaIIbbeta3 was activated
      by the monoclonal antibody PT25-2: rupture forces of 20-60 pN with an
      exponentially decreasing probability of detection and rupture forces in the range
      of 60-150 pN with a maximum at approximately 70-80 pN. Both rupture force regimes
      were specific for fibrinogen binding to the activated conformation of
      alphaIIbbeta3 because they were inhibited by alphaIIbbeta3-specific antagonists.
      Identical rupture force regimes were present constitutively when cells expressing
      the alphaIIb and beta3 transmembrane domain mutants were studied, confirming that
      these mutations induced an active alphaIIbbeta3 conformation. Moreover, there
      were no significant differences in the yield strength of the low-to-moderate and
      strong force regimes when alphaIIbbeta3 was activated by PT25-2 or the
      transmembrane domain mutations, implying that there was no fundamental difference
      in the way these forms of activated alphaIIbbeta3 interacted with fibrinogen.
      Thus, the two-step pathway of the interaction of alphaIIbbeta3 with fibrinogen we
      have identified appears to be a fundamental property of the high-affinity state
      of alphaIIbbeta3 and is identical regardless of whether this affinity state is
      achieved by intracellular, extracellular, or membrane-associated events.

PMID- 16605262
TI  - Rapid binding of T7 RNA polymerase is followed by simultaneous bending and
      opening of the promoter DNA.
AB  - To form a functional open complex, bacteriophage T7 RNA polymerase (RNAP) binds
      to its promoter DNA and induces DNA bending and opening. The objective of this
      study was to elucidate the temporal coupling in DNA binding, bending, and opening
      processes that occur during initiation. For this purpose, we conducted a combined
      measurement of stopped-flow fluorescence anisotropy, fluorescence resonance
      energy transfer (FRET), and 2-aminopurine fluorescence. Stopped-flow anisotropy
      measurements provided direct evidence of an intermediate resulting from rapid
      binding of the promoter to T7 RNA polymerase. Stopped-flow FRET measurements
      showed that promoter bending occurred at a rate constant that was slower than the
      initial DNA binding rate constant, indicating that the initial complex was not
      significantly bent. Similarly, stopped-flow 2-aminopurine fluorescence changes
      showed that promoter opening occurred at a rate constant that was slower than the
      initial DNA binding rate constant, indicating that the initial complex was not
      significantly melted. The indistinguishable observed rate constants of FRET and 2
      aminopurine fluorescence changes indicate that DNA bending and opening processes
      are temporally coupled and these DNA conformational changes take place after the
      DNA binding step. The results in this paper are consistent with the mechanism in
      which the initial binding of T7 RNAP to the promoter results in a closed complex,
      which is then converted into an open complex in which the promoter is both
      sharply bent and melted.

PMID- 16605264
TI  - Effects of mutagenesis of W343 in human annexin A6 isoform 1 on its interaction
      with GTP: nucleotide-induced oligomer formation and ion channel activity.
AB  - Accumulated experimental evidence suggests that annexin A6 (AnxA6) is involved in
      ion transport in various tissues. Such a biological function is related either to
      the modulation of ion transport systems by AnxA6 or to the ion channel activity
      of the protein. While AnxA6 channel activity at low pH seems to be associated
      with a large conformational transition in the protein, the mechanism of GTP
      induced ion channel formation remains obscure. This activity is not accompanied
      by changes in protein structure. The existence of a domain binding the phosphate
      groups of GTP in AnxA6 [Bandorowicz-Pikula, J., Kirilenko, A., van Deursen, R.,
      Golczak, M., Kuhnel, M., Lancelin, J. M., Pikula, S., and Buchet, R. (2003)
      Biochemistry 42, 9137-9146] may provide some clues about the molecular mechanisms
      of GTP-induced ion channel formation. In addition, we observed that one of the
      AnxA6 tryptophan residues, W192 or W343, may be involved in GTP binding.
      Therefore, we created several site-directed mutants of AnxA6 in which selected
      amino acid residues within a consensus sequence of a putative nucleotide-binding
      domain of AnxA6 were replaced with other amino acid residues without affecting
      the overall structure of protein as examined by circular dichroism and infrared
      spectroscopies. Their properties were analyzed and compared to those of the
      native protein. In contrast to mutant W192S and wild-type annexin, mutant W343S
      neither bound GTP nor exhibited GTP-induced ion channel activity. In addition, we
      detected the likely formation of AnxA6 trimers in the presence of GTP. The
      ability of mutant W343S to form trimers was significantly impaired. Our findings
      suggest that W343 participates in the formation of AnxA6 trimers. We hypothesize
      that such trimers could lead to a functional unit of the GTP-induced ion channels
      formed by the annexin molecules.

PMID- 16605265
TI  - Rhodopsin photointermediates in two-dimensional crystals at physiological
      temperatures.
AB  - Bovine rhodopsin photointermediates formed in two-dimensional (2D) rhodopsin
      crystal suspensions were studied by measuring the time-dependent absorbance
      changes produced after excitation with 7 ns laser pulses at 15, 25, and 35
      degrees C. The crystalline environment favored the Meta I(480) photointermediate,
      with its formation from Lumi beginning faster than it does in rhodopsin membrane
      suspensions at 35 degrees C and its decay to a 380 nm absorbing species being
      less complete than it is in the native membrane at all temperatures. Measurements
      performed at pH 5.5 in 2D crystals showed that the 380 nm absorbing product of
      Meta I(480) decay did not display the anomalous pH dependence characteristic of
      classical Meta II in the native disk membrane. Crystal suspensions bleached at 35
      degrees C and quenched to 19 degrees C showed that a rapid equilibrium existed on
      the approximately 1 s time scale, which suggests that the unprotonated
      predecessor of Meta II in the native membrane environment (sometimes called
      MII(a)) forms in 2D rhodopsin crystals but that the non-Schiff base proton uptake
      completing classical Meta II formation is blocked there. Thus, the 380 nm
      absorbance arises from an on-pathway intermediate in GPCR activation and does not
      result from early Schiff base hydrolysis. Kinetic modeling of the time-resolved
      absorbance data of the 2D crystals was generally consistent with such a
      mechanism, but details of kinetic spectral changes and the fact that the
      residuals of exponential fits were not as good as are obtained for rhodopsin in
      the native membrane suggested the photoexcited samples were heterogeneous.
      Variable fractional bleach due to the random orientation of linearly dichroic
      crystals relative to the linearly polarized laser was explored as a cause of
      heterogeneity but was found unlikely to fully account for it. The fact that the
      380 nm product of photoexcitation of rhodopsin 2D crystals is on the
      physiological pathway of receptor activation suggests that determination of its
      structure would be of interest.

PMID- 16605266
TI  - Albumin binding to FcRn: distinct from the FcRn-IgG interaction.
AB  - The MHC-related Fc receptor for IgG (FcRn) protects albumin and IgG from
      degradation by binding both proteins with high affinity at low pH in the acid
      endosome and diverting both from a lysosomal pathway, returning them to the
      extracellular compartment. Immunoblotting and surface plasmon resonance studies
      show that both IgG and albumin bind noncooperatively to distinct sites on FcRn,
      that the affinity of FcRn for albumin decreases approximately 200-fold from
      acidic to neutral pH, and that the FcRn-albumin interaction shows rapid
      association and dissociation kinetics. Isothermal titration calorimetry shows
      that albumin binds FcRn with a 1:1 stoichiometry and the interaction has
      hydrophobic features as evidenced by a large positive change in entropy upon
      binding. Our results suggest that the FcRn-albumin interaction has unique
      features distinct from FcRn-IgG binding despite the overall similarity in the pH
      dependent binding mechanism by which both ligands are protected from degradation.

PMID- 16605267
TI  - The disulfide bridge in the head domain of rhodobacter sphaeroides cytochrome c1
      is needed to maintain its structural integrity.
AB  - Cytochrome c(1) of Rhodobacter sphaeroides ubiquinol-cytochrome c oxidoreductase
      contains several insertions and deletions that distinguish it from the complex of
      other higher organisms. Additionally, this bacterial cytochrome c(1) contains two
      nonconserved cysteines, C145 and C169, with the latter included in the second
      long insertion located upstream of the sixth heme ligand, M185. The orientation
      of the insertions and the state of these non-heme binding cysteines remain
      unknown. Mutating one or both cysteines is found to have comparable effects on
      the functionality of the cytochrome bc(1) complex. Mutants show an electron
      transfer activity decreased to a rate that is still high enough to support
      delayed photosynthetic growth. The mutated cytochrome c(1) has a decreased E(m)
      without any alteration in the heme ligation environment since none of the mutants
      binds carbon monoxide. The low E(m) is believed to be caused by a structural
      modification in the head domain of cytochrome c(1). Analysis of the mutants
      reveals that the two cysteines form a disulfide bridge. Cleavage of cytochrome
      c(1) between the two cysteines followed by gel electrophoresis shows two
      fragments only under reducing conditions, confirming the existence of a disulfide
      bridge. The disulfide bridge is essential in maintaining the structural integrity
      of cytochrome c(1) and thus the functionality of the cytochrome bc(1) complex.

PMID- 16605269
TI  - Properties of the cysteine residues and the iron-sulfur cluster of the
      assimilatory 5'-adenylyl sulfate reductase from Enteromorpha intestinalis.
AB  - The 5'-adenylyl sulfate (APS) reductase from the marine macrophytic green alga
      Enteromorpha intestinalis uses reduced glutathione as the electron donor for the
      reduction of APS to 5'-AMP and sulfite. The E. intestinalis enzyme (EiAPR) is
      composed of a reductase domain and a glutaredoxin-like C-terminal domain. The
      enzyme contains a single [4Fe-4S] cluster as its sole prosthetic group. Three of
      the enzyme's eight cysteine residues (Cys166, Cys257, and Cys260) serve as
      ligands to the iron-sulfur cluster. Site-directed mutagenesis experiments and
      resonance Raman spectroscopy are consistent with the presence of a cluster in
      which only three of the four ligands to the cluster irons contributed by the
      protein are cysteine residues. Site-directed mutagenesis experiments suggest that
      the thiol group of Cys250, a residue found only in algal APS reductases, is not
      an absolute requirement for activity. The other four cysteines that do not serve
      as cluster ligands, all of which are required for activity, are involved in the
      formation of two redox-active disulfide/dithiol couples. The couple involving
      Cys342 and Cys345 has an E(m) value at pH 7.0 of -140 mV, and the one involving
      Cys165 and Cys285 has an E(m) value at pH 7.0 of -290 mV. The C-terminal portion
      of EiAPR, expressed separately, exhibits the cystine reductase activity
      characteristic of glutaredoxins. It is proposed that the Cys342-Cys345 disulfide
      provides the site for entry of electrons from reduced glutathione and that the
      Cys166-Cys285 disulfide may serve as a structural element that is essential for
      keeping the enzyme in the catalytically active conformation.

PMID- 16605268
TI  - Peroxidase activity and structural transitions of cytochrome c bound to
      cardiolipin-containing membranes.
AB  - During apoptosis, cytochrome c (cyt c) is released from intermembrane space of
      mitochondria into the cytosol where it triggers the caspase-dependent machinery.
      We discovered that cyt c plays another critical role in early apoptosis as a
      cardiolipin (CL)-specific oxygenase to produce CL hydroperoxides required for
      release of pro-apoptotic factors [Kagan, V. E., et al. (2005) Nat. Chem. Biol. 1,
      223-232]. We quantitatively characterized the activation of peroxidase activity
      of cyt c by CL and hydrogen peroxide. At low ionic strength and high CL/cyt c
      ratios, peroxidase activity of the CL/cyt c complex was increased >50 times. This
      catalytic activity correlated with partial unfolding of cyt c monitored by
      Trp(59) fluorescence and absorbance at 695 nm (Fe-S(Met(80)) band). The
      peroxidase activity increase preceded the loss of protein tertiary structure.
      Monounsaturated tetraoleoyl-CL (TOCL) induced peroxidase activity and unfolding
      of cyt c more effectively than saturated tetramyristoyl-CL (TMCL). TOCL/cyt c
      complex was found more resistant to dissociation by high salt concentration.
      These findings suggest that electrostatic CL/cyt c interactions are central to
      the initiation of the peroxidase activity, while hydrophobic interactions are
      involved when cyt c's tertiary structure is lost. In the presence of CL, cyt c
      peroxidase activity is activated at lower H(2)O(2) concentrations than for
      isolated cyt c molecules. This suggests that redistribution of CL in the
      mitochondrial membranes combined with increased production of H(2)O(2) can switch
      on the peroxidase activity of cyt c and CL oxidation in mitochondria-a required
      step in execution of apoptosis.

PMID- 16605270
TI  - Direct detection and kinetic analysis of covalent intermediate formation in the 4
      amino-4-deoxychorismate synthase catalyzed reaction.
AB  - Chorismate-utilizing enzymes catalyze diverse reactions, providing critical
      physiological functions unique to plants, bacteria, fungi, and some parasites.
      Their absence in animals makes them excellent targets for antimicrobials and
      herbicides. 4-Amino-4-deoxychorismate synthase (ADCS) catalyzes the first step in
      folate biosynthsis and shares a common core mechanism with isochorismate synthase
      (IS) and anthranilate synthase (AS), in which nucleophile addition at C2
      initiates these reactions. Evidence was presented previously [He, Z., Stigers
      Lavoie, K. D., Bartlett, P. A., and Toney, M. D. (2004) J. Am. Chem. Soc. 126,
      2378-2385] that K274 is the nucleophile in ADCS, implying formation of a covalent
      intermediate. Herein, we report the direct detection of this covalent
      intermediate formed in ADCS-catalyzed reactions by ESI-MS. Difference spectra
      show the covalent intermediate has an absorption maximum at 310 nm. This was used
      to study the pre-steady-state kinetics of covalent intermediate formation under
      various conditions. Additionally, E258 in ADCS was shown to be critical to
      formation of the covalent intermediate by acting as a general acid catalyst for
      loss of the C4 hydroxyl group. The E258A/D mutants both exhibit very low
      activity. Acetate is a poor chemical rescue agent for E258D but an excellent one
      for E258A, with a 20000-fold and 3000-fold rate increase for Gln-dependent and
      NH(4)(+)-dependent activities, respectively. Lastly, A213 in IS (structurally
      homologous to K274 in ADCS) was changed to lysine in an attempt to convert IS to
      an ADCS-like enzyme. HPLC studies support the formation of a covalent
      intermediate with this mutant.

PMID- 16605271
TI  - Regulation of the activity and fatty acid specificity of lecithin-cholesterol
      acyltransferase by sphingomyelin and its metabolites, ceramide and ceramide
      phosphate.
AB  - Sphingomyelin (SM), the second most abundant phospholipid in plasma lipoproteins,
      was previously shown to be a physiological inhibitor of the lecithin-cholesterol
      acyltransferase (LCAT) reaction. In this study, we investigated the effects of
      its metabolites, ceramide and ceramide phosphate, on the activity and fatty acid
      specificity of LCAT in vitro. Treatment of SM-containing substrate with SMase C,
      which hydrolyzes SM to ceramide, abolished the inhibitory effect of SM, whereas
      treatment with SMase D, which hydrolyzes it to ceramide phosphate, increased the
      level of inhibition. Although incorporation of ceramide into the substrate in the
      absence of SM activated the LCAT reaction only modestly, its co-incorporation
      with SM neutralized the inhibitory effect of SM. Ceramide phosphate, on the other
      hand, inhibited the LCAT reaction more strongly than SM. The effects of the
      sphingolipids on the phospholipase A and cholesterol esterification reactions of
      the enzyme were similar, indicating that they regulate the binding of
      phosphatidylcholine (PC) to the active site, rather than the esterification step.
      Incorporation of ceramide into the substrate stimulated the synthesis of
      unsaturated cholesteryl esters at the expense of saturated esters. However, these
      effects on fatty acid specificity disappeared when the PC substrates were
      incorporated into an inert diether PC matrix, suggesting that ceramide increases
      the availability of polyunsaturated PCs to the enzyme by altering the
      macromolecular structure of the substrate particle. Since the plasma ceramide
      levels are increased during inflammation, these results indicate that the
      activity and fatty acid specificity of LCAT may be altered during the
      inflammatory response.

PMID- 16605272
TI  - Examination of the premelting transition of DNA A-tracts using a fluorescent
      adenosine analogue.
AB  - The fluorescent adenosine analogue 4-amino-8-(2-deoxy-beta-d-ribofuranosyl)-5'-O
      dimethoxytrityl-6-methyl-7(8H)-pteridone (6MAP) has been used to perform residue
      specific analyses of DNA A-tracts during the premelting transition. DNA A-tracts,
      which exhibit sequence-induced curvature, adopt a B-DNA conformation as a
      function of increasing temperature. Fluorescence melting curves indicate that
      6MAP is a more sensitive reporter of the premelting transition than UV absorption
      spectroscopy. Further, residue specific fluorescence analyses of A-tract and
      control duplexes reveal that some of the conformational changes associated with
      the premelting transition occur within A-tract regions. Analyses of the
      energetics of the premelting transition indicate that ApA steps make a larger
      enthalpic contribution to the premelting transition than ApT steps. To explore
      the effect of cations on the premelting transition, fluorescence melts were
      performed in the presence of NH(4)(+), Mg(2+), and low (0.05 M) and high (0.5 M)
      concentrations of Na(+). These studies show that the fluorescence intensity
      changes associated with the premelting transition are sensitive to cation type
      and concentration and are larger and more pronounced in the presence of 0.5 M
      Na(+), NH(4)(+), and Mg(2+). Incorporation of 6MAP into longer duplexes
      containing phased A-tracts shows that the local environment of adenosines in
      phased A-tracts is similar to that of individual A-tracts. Fluorescence quenching
      results indicate that ApA and ApT steps within A-tracts are less solvent exposed
      than their counterparts in control sequence isomers, possibly because of the
      narrowed minor groove of A-tract sequences.

PMID- 16605273
TI  - Replication of an oxidized abasic site in Escherichia coli by a dNTP-stabilized
      misalignment mechanism that reads upstream and downstream nucleotides.
AB  - Abasic sites (AP) and oxidized abasic lesions are often referred to as
      noninstructive lesions because they cannot participate in Watson-Crick base
      pairing. The aptness of the term noninstructive for describing AP site
      replication has been called into question by recent investigations in E. coli
      using single-stranded shuttle vectors. These studies revealed that the
      replication of templates containing AP sites or the oxidized abasic lesions
      resulting from C1'- (L) and C4'-oxidation (C4-AP) are distinct from one another,
      suggesting that structural features other than Watson-Crick hydrogen bonds
      contribute to controlling replication. The first description of the replication
      of the abasic site resulting from formal C2'-oxidation (C2-AP) is presented here.
      Full-length and single-nucleotide deletion products are observed when templates
      containing C2-AP are replicated in E. coli. Single nucleotide deletion formation
      is largely dependent upon the concerted effort of pol II and pol IV, whereas pol
      V suppresses frameshift product formation. Pol V utilizes the A-rule when
      bypassing C2-AP. In contrast, pol II and pol IV utilize a dNTP-stabilized
      misalignment mechanism to read the upstream and downstream nucleotides when
      bypassing C2-AP. This is the first example in which the identity of the 3'
      adjacent nucleotide is read during the replication of a DNA lesion. The results
      raise further questions as to whether abasic lesions are noninstructive lesions.
      We suggest that abasic site bypass is affected by the local biopolymer structure
      in addition to the structure of the lesion.

PMID- 16605274
TI  - Interrelationships of glycosylation and aggregation kinetics for Peniophora lycii
      phytase.
AB  - The kinetics of thermally induced aggregation of the glycoprotein Peniophora
      lycii phytase (Phy) and a deglycosylated form (dgPhy) was studied by dynamic
      (DLS) and static (SLS) light scattering. This provided a detailed insight into
      the time course of the formation of small aggregates ( approximately 10-100
      molecules) of the enzyme. The thermodynamic stability of the two forms was also
      investigated using scanning calorimetry (DSC). It was found that the glycans
      strongly promoted kinetic stability (i.e., reduced the rate of irreversible
      denaturation) while leaving the equilibrium denaturation temperature, T(d),
      defined by DSC, largely unaltered. At pH 4.5-5.0, for example, dgPhy aggregated
      approximately 200 times faster than Phy, even though the difference in T(d) was
      only 1-3 degrees C. To elucidate the mechanism by which the glycans promote
      kinetic stability, we measured the effect of ionic strength and temperature on
      the aggregation rate. Also, the second virial coefficients (B(22)) for the two
      forms were measured by SLS. These results showed that the aggregation rate of Phy
      scaled with the concentration of thermally denatured protein. This suggested
      first-order kinetics with respect to the concentration of the thermally denatured
      state. A similar but less pronounced correlation was found for dgPhy, and it was
      suggested that while the aggregation process for the deglycosylated form is
      dominated by denatured protein, it also involves a smaller contribution from
      associating molecules in the native state. The measurements of B(22) revealed
      that dgPhy had slightly higher values than Phy. This suggests that dgPhy
      interacts more favorably with the buffer than Phy and hence rules out strong
      hydration of the glycans as the origin of their effect on the kinetic stability.
      On the basis of this and the effects of pH and ionic strength, we suggest that
      the inhibition of aggregation is more likely to depend on steric hindrance of the
      glycans in the aggregated form of the protein.

PMID- 16605275
TI  - The intrinsically unstructured domain of PC4 modulates the activity of the
      structured core through inter- and intramolecular interactions.
AB  - Proteins frequently contain unstructured regions apart from a functionally
      important and well-conserved structured domain. Functional and structural aspects
      for these regions are frequently less clear. The general human positive cofactor
      4 (PC4), has such a domain organization and can interact with various DNA
      substrates, transcriptional activators, and basal transcription factors. While
      essential for the cofactor function, structural and functional knowledge about
      these interactions is limited. Using biochemical, nuclear magnetic resonance
      (NMR), and docking experiments, we show that the carboxy-terminal structured core
      domain (PC4ctd) is required and sufficient for binding to single-stranded DNA
      (ssDNA), double-stranded DNA (dsDNA), and the herpes simplex virion protein 16
      (VP16) activation domain (VP16ad). We determined the interaction surfaces within
      PC4 and showed that VP16 and DNA binding are mutually exclusive. Although the
      amino-terminal domain of PC4 (PC4ntd) alone is devoid of any bioactivity, it
      increases the interaction with VP16ad. While it decreases the ssDNA-binding and
      DNA-unwinding activity, it does not influence dsDNA binding. Structural
      characterization of this domain showed that it is highly flexible and mostly
      unstructured both in the free form and in the complex. NMR titration experiments
      using various protein and DNA substrates of the individual domains and the full
      length PC4 revealed local conformational or environmental changes in both the
      structured and unstructured subdomains, which are interpreted to be caused by
      inter- and intramolecular interactions. We propose that the unstructured PC4ntd
      regulates the PC4 cofactor function by specific interactions with the activator
      and through modulation and/or shielding of the interaction surface in the
      structured core of PC4ctd.

PMID- 16605277
TI  - Rationing of drugs for rare diseases.

PMID- 16605279
TI  - The burden of age-related macular degeneration.
AB  - As age-related macular degeneration (AMD) becomes more prevalent as a result of
      longer life expectancy and the number of elderly people worldwide, it will become
      increasingly important to understand its potential health and economic impact for
      appropriate healthcare planning. This review identified published literature on
      costs and resource use associated with AMD. Despite the increasing prevalence of
      AMD, the worldwide burden of illness is unknown. Several studies of direct
      medical costs, both those associated with ophthalmic care and those associated
      with other care, have been conducted and have identified increased medical care
      associated with AMD. Direct non-medical costs include the cost for vision aids;
      while these costs may be substantial, they are difficult to quantify as no
      comprehensive sources track the distribution or use of vision aids. Because AMD
      is uncommon among people of working age, there is less concern regarding the
      impact of indirect (workplace) costs among AMD patients. However, indirect costs
      are incurred by caregivers who leave the workforce early or change their work
      patterns in order to provide assistance to AMD patients; the magnitude of
      caregiver-related costs is unknown. The cost effectiveness of some interventions
      for AMD has been explored. Supplementation with zinc and antioxidants for non
      exudative (dry) AMD has been shown to result in an acceptable cost per QALY and
      is considered cost effective. Studies suggest that laser photocoagulation is cost
      effective but that photodynamic therapy with verteporfin appears to be cost
      effective only among patients with good visual acuity at baseline or when models
      extend longer than 5 years. Further research is needed to integrate the
      information on various components of AMD-related costs into a comprehensive
      burden of illness estimate and to evaluate basic utility assumptions in existing
      models.

PMID- 16605280
TI  - Economic and developmental considerations for pharmacogenomic technology.
AB  - The pharmaceutical industry's core business is the innovation, development and
      marketing of new drugs. Pharmacogenetic (PG) testing and technology has the
      potential to increase a drug's value in many ways. A critical issue for the
      industry is whether products in development should be teamed with genetic tests
      that could segment the total population into responders and non-responders. In
      this paper we use a cost-effectiveness framework to model the strategic decision
      making considerations by pharmaceutical manufacturers as they relate to drug
      development and the new technology of PG (the science of using genetic markers to
      predict drug response). In a simple, static, one-period model we consider three
      drug development strategies: a drug is exclusively developed and marketed to
      patients with a particular genetic marker; no distinguishing among patients based
      on the expression of a genetic marker is made (traditional approach); and a
      strategy whereby a drug is marketed to patients both with and without the genetic
      marker but there is price discrimination between the two subpopulations. We
      developed three main principles: revenues under a strategy targeting only the
      responder subpopulation will never generate more revenue than that which could
      have been obtained under a traditional approach; total revenues under a targeted
      PG strategy will be less than that under a traditional approach but higher than a
      naive [corrected] view would believe them to be; and a traditional [corrected]
      approach will earn the same total revenues as a price discrimination strategy,
      assuming no intermarket arbitrage. While these principles relate to the singular
      (and quite narrow) consideration of drug revenues, they may nevertheless
      partially explain why PG is not being used as widely as was predicted several
      years ago when the technology first became available, especially in terms of
      pharmaceutical manufacturer-developed tests.

PMID- 16605281
TI  - Optimal assignment of treatments to health states using a Markov decision model:
      an introduction to basic concepts.
AB  - Assessing the cost effectiveness of a new health intervention often requires
      modelling to estimate the impact of the intervention on cost, survival and
      quality of life over the lifetime of a cohort of patients. Markov modelling is a
      methodology that is commonly employed to estimate these long-term costs and
      benefits. As commonly used, these models assume that the patients continue to get
      the treatments assigned regardless of the change in health states. In this paper,
      we describe an extension to the Markov modelling approach, called Markov decision
      modelling. Such a model starts with a set of health states and treatments and
      optimally assigns treatments to each of the health states. A Markov decision
      model can be used to identify the optimal treatment strategy not just for the
      initial disease state, but also as the disease state changes over time. We
      present a dynamic programming approach to identifying the optimal assignment of
      treatments, and illustrate this methodology using an example. The Markov decision
      modelling approach provides an efficient way of identifying optimal assignment of
      treatments to health states, but, like the standard Markov model, may be of
      limited use when probabilities of future events depend on past history in a
      complex fashion. Even with its limitations, Markov decision models offer an
      opportunity for health economists to inform healthcare decision-makers on how to
      modify current treatment pathways to incorporate new treatments as they become
      available.

PMID- 16605282
TI  - Good practice guidelines for decision-analytic modelling in health technology
      assessment: a review and consolidation of quality assessment.
AB  - The use of decision-analytic modelling for the purpose of health technology
      assessment (HTA) has increased dramatically in recent years. Several guidelines
      for best practice have emerged in the literature; however, there is no agreed
      standard for what constitutes a 'good model' or how models should be formally
      assessed. The objective of this paper is to identify, review and consolidate
      existing guidelines on the use of decision-analytic modelling for the purpose of
      HTA and to develop a consistent framework against which the quality of models may
      be assessed. The review and resultant framework are summarised under the three
      key themes of Structure, Data and Consistency. 'Structural' aspects relate to the
      scope and mathematical structure of the model including the strategies under
      evaluation. Issues covered under the general heading of 'Data' include data
      identification methods and how uncertainty should be addressed. 'Consistency'
      relates to the overall quality of the model. The review of existing guidelines
      showed that although authors may provide a consistent message regarding some
      aspects of modelling, such as the need for transparency, they are contradictory
      in other areas. Particular areas of disagreement are how data should be
      incorporated into models and how uncertainty should be assessed. For the purpose
      of evaluation, the resultant framework is applied to a decision-analytic model
      developed as part of an appraisal for the National Institute for Health and
      Clinical Excellence (NICE) in the UK. As a further assessment, the review based
      on the framework is compared with an assessment provided by an independent
      experienced modeller not using the framework. It is hoped that the framework
      developed here may form part of the appraisals process for assessment bodies such
      as NICE and decision models submitted to peer review journals. However, given the
      speed with which decision-modelling methodology advances, there is a need for its
      continual update.

PMID- 16605283
TI  - Post-exposure influenza prophylaxis with oseltamivir: cost effectiveness and cost
      utility in families in the UK.
AB  - OBJECTIVES: To assess the cost effectiveness and cost utility of preventing post
      exposure influenza infection using the neuraminidase inhibitor oseltamivir from a
      healthcare payer's perspective in the UK. METHODS: A simulation model was
      developed, based on clinical trial results and published data, to predict
      morbidity and mortality due to influenza and to compare oseltamivir post-exposure
      prophylaxis (PEP) with no prophylaxis within families with members aged >or=13
      years. Two scenarios were tested:1. Comparison of patients receiving PEP versus
      patients not receiving PEP and not being treated with oseltamivir should they
      become infected. 2. Comparison of patients receiving PEP versus patients not
      receiving PEP but being treated with oseltamivir should they become infected. The
      model was run with an attack rate in household contacts of 8% for the base case,
      with higher rates (up to 30%, representing pandemic conditions) tested in
      sensitivity analyses. A societal perspective and other key parameters were tested
      in sensitivity analysis. The year of costing was 2002. The time span for the
      model was up to 1 year (including one influenza season), but loss of life was
      included in the QALY calculation and based on expected life expectancy. RESULTS:
      PEP with oseltamivir results in reduced morbidity (i.e. fewer influenza cases)
      and associated reductions in complications, hospitalisations and mortality due to
      influenza. When comparing oseltamivir PEP with no prophylaxis for contact attack
      rates of 8%, 12% and 30%, the mean costs per QALY gained for scenario one were
      estimated at 29,938 pounds, 18,697 pounds and 5403 pounds, respectively; the mean
      costs per case avoided were 467 pounds, 293 pounds and 84 pounds, respectively.
      The corresponding results for scenario two were 52,202 pounds, 31,610 pounds and
      9688 pounds per QALY gained. CONCLUSIONS: PEP with oseltamivir is likely to be a
      cost-effective strategy for family contacts in the UK from a healthcare payer
      perspective when influenza-like illness contact attack rates are 8% or higher and
      the only treatment given is 'usual care'.

PMID- 16605284
TI  - A cost-utility analysis of losartan versus atenolol in the treatment of
      hypertension with left ventricular hypertrophy.
AB  - INTRODUCTION: The LIFE (Losartan Intervention For Endpoint reduction in
      hypertension) study demonstrated a 13% relative risk reduction in the primary
      composite endpoint (myocardial infarction, stroke or death) for patients with
      hypertension and electrocardiographically diagnosed left ventricular hypertrophy
      (LVH) treated with losartan compared with atenolol. Losartan recipients also had
      a 25% relative risk reduction for stroke compared with atenolol recipients.
      Incorporating the results found in the LIFE study into an economic model, an
      incremental cost-effectiveness analysis was performed comparing losartan with
      atenolol in the treatment of 67-year old patients with hypertension and LVH.
      METHODS: A Markov state transition model, based on published results of the LIFE
      trial (mean follow-up of 4.8 years), was utilised to extrapolate the outcomes
      observed in this trial to the patients' lifetime. Utility estimates for the
      associated health states were obtained from various published sources. Lifetime
      treatment costs were calculated adopting a societal perspective. Both costs and
      benefits were discounted and incremental cost-effectiveness ratios (ICERs) were
      estimated. One-way and probabilistic sensitivity analyses were performed.
      RESULTS: The estimated ICER for losartan versus atenolol was 1337 Canadian
      dollars per QALY gained (1 Canadian dollar =0.75 US dollars, 2002 values). This
      ICER was robust to extensive sensitivity analysis, demonstrating a 95%
      probability that the ICER would be <20,000 Canadian dollars per QALY gained.
      CONCLUSION: From a Canadian societal perspective, losartan appears to be a cost
      effective alternative to atenolol in patients with hypertension and LVH. The
      estimated ICERs, including the sensitivity analyses, were within the range of
      cost-effectiveness ratios for various currently funded interventions and drugs in
      developed countries.

PMID- 16605285
TI  - Productivity costs in health-state valuations : does explicit instruction matter?
AB  - BACKGROUND: There has been considerable debate on whether productivity costs
      should be captured in the numerator or the denominator of the cost-effectiveness
      ratio. That debate cannot be resolved on the basis of theoretical arguments alone
      because the final choice also depends on what is incorporated in health-state
      valuations by respondents and how this influences outcomes. At the moment, little
      is known about whether the effects of ill health on income are included in health
      state valuations, and how instructions on including or excluding the effects on
      income influence health-state valuations. AIM: To conduct an empirical study of
      health-state valuations to test: (i) whether or not respondents spontaneously
      include the effect of ill health on income and leisure time; (ii) the impact on
      the valuation of inclusion (or exclusion) of such effects; and (iii) the
      influence of explicit instructions on this matter. METHODS: Three questionnaires
      were developed and administered to the general public. Health-state valuations
      were conducted by visual analogue scale scoring of three health states of
      differing severity taken from the EQ-5D. Version 1 had no directions regarding
      inclusion/exclusion of effects of ill health on income. Those respondents who
      spontaneously included effects on income were subsequently asked to value the
      same three health states again, excluding these effects. Version 2 had explicit
      instructions to incorporate the effects on income. Version 3 stated that income
      was assumed to not change as a result of ill health. Respondents for versions 2
      and 3 were also questioned about inclusion of effects on leisure time. RESULTS:
      Giving explicit instructions on the incorporation or exclusion of effects of ill
      health on income did not lead to significant differences in subsequent health
      state valuations. In the absence of instruction, 36% of respondents included and
      64% excluded effects on income, but the health-state valuations of the two groups
      were not significantly different. Eighty-four percent of respondents included the
      effects of ill health on leisure activities, and again this had no significant
      impact on the resulting health-state valuations. CONCLUSIONS: It appears that
      neither spontaneous differences in incorporation of effects on income, nor
      explicit instructions will yield significantly different health-state valuations.
      This may suggest that QALY measures are insensitive to concerns regarding effects
      on income even when these are (explicitly) incorporated, and these effects may
      therefore be best placed on the cost side of the cost-effectiveness ratio.

PMID- 16605286
TI  - Quality-of-life valuations of advanced breast cancer by New Zealand women.

PMID- 16605288
TI  - Cutaneous manifestations of internal malignancy: diagnosis and management.
AB  - An association between systemic malignancy and cutaneous manifestations has long
      been recognized. The cutaneous features that can occur are numerous and
      heterogeneous, and many different etiologic mechanisms are represented - from
      direct tumor invasion of skin or distant metastases to a wide variety of
      inflammatory dermatoses that may occur as paraneoplastic phenomena. In addition,
      there are a number of inherited syndromes that carry an increased risk of
      cutaneous as well as internal malignancies. While some of these inherited
      syndromes and paraneoplastic phenomena are exceedingly rare, all clinicians will
      be aware of the common cutaneous manifestations of advanced malignant disease
      such as generalized xerosis and pruritus. This review classifies these wide
      ranging cutaneous manifestations of internal malignancy into five basic groups
      and provides practical advice regarding diagnosis and screening of patients who
      initially present with a cutaneous complaint. Also included is up-to-date
      information on two rapidly expanding and exciting areas of research that are
      likely to have far-reaching clinical implications: (i) clarification of
      underlying humoral mechanisms, for example, in the malignant carcinoid syndrome;
      and (ii) identification of an increasing number of specific genetic defects that
      confer a susceptibility to malignancy.Increased clinician awareness regarding the
      associations between these lesions and internal malignancy or inherited syndromes
      will facilitate screening and early diagnosis.

PMID- 16605289
TI  - Receptor-selective retinoids for psoriasis: focus on tazarotene.
AB  - Topical and oral retinoids have been successfully used in antipsoriatic therapy
      over the last 50 years. Development of more selective agents has led to an
      improved efficacy and safety profile. The first topical receptor-selective
      retinoid to be approved for the treatment of plaque psoriasis is tazarotene.
      Topical tazarotene displays an onset of action and efficacy similar to those of
      other established antipsoriatic agents. Common adverse events of this agent such
      as pruritus, burning, local skin irritation, and erythema are limited to the skin
      and generally mild or moderate in severity. Although effective as monotherapy,
      evidence is accumulating that combining topical tazarotene with other established
      antipsoriatic therapies results in enhanced efficacy and reduced adverse events.
      In particular, concomitant use of topical tazarotene with a mid-potency or high
      potency corticosteroid in the treatment of psoriatic plaques enhances efficacy
      and reduces the risk of corticosteroid-induced skin atrophy. Combination of
      phototherapy with tazarotene accelerates the clinical response and diminishes the
      cumulative UVB or psoralen plus UVA (PUVA) exposure load. Recently, an oral form
      of tazarotene has been developed. The results of completed phase III clinical
      trials of this agent indicate a beneficial effect in moderate to severe plaque
      psoriasis. Adverse events are generally of mild severity, and most of those
      observed, such as cheilitis and dry skin, are typical of hypervitaminosis A. Of
      note, oral tazarotene appears not to be associated with other adverse events that
      are typical of oral retinoids, including hypertriglyceridemia and
      hypercholesterolemia. However, since head-to-head trials with acitretin (the only
      retinoid currently approved for systemic therapy) have not been conducted, it is
      unclear whether tazarotene is any safer or more effective than acitretin.
      Moreover, the major drawback of oral tazarotene is teratogenicity, which may
      limit its use in female patients. Further studies evaluating long-term clinical
      outcomes with oral tazarotene and its use in combination therapies are awaited.

PMID- 16605290
TI  - Assessing quality of life in patients with acne vulgaris: implications for
      treatment.
AB  - Diagnosing acne is easy. However, treatment must be adapted to the type and
      severity of acne, and must also take into account the impact of acne on patients'
      quality of life. As there is not always a correlation between the severity of
      acne and its impact on quality of life, it can be helpful for the dermatologist
      to use a quality of life scale to determine the psychological impact of acne on
      patients. Either global scales or specific scales for acne can be used. This
      article reviews the different scales used for evaluation of quality of life in
      patients with acne.Consideration of specific scales suggests that the Acne
      Disability Index/Cardiff Acne Disability Index is the easiest scale to use in
      routine dermatology practice. The Acne Quality of Life scale is particularly
      useful for evaluating anxiety and depression. The Acne-Specific Quality of Life
      questionnaire has been mainly validated in adult acne. The Assessment of the
      Psychological and Social Effects of Acne scale has yet to be validated. Clinical
      trials indicate that use of global and specific scales together has complementary
      benefits. In the management of acne, evaluation of quality of life may help to
      detect depression in teenagers. It may also help to enhance adherence to
      treatment, which is a crucial factor for success. Finally, there are now
      validated quality of life scales that are easy to use during patient
      consultations (taking <2 minutes to complete) by clinicians wishing to evaluate
      quality of life in patients with acne.

PMID- 16605291
TI  - Techniques for soft tissue augmentation: an 'a to z'.
AB  - As society continues to seek the most opportune means to preserve youthful looks,
      an interest in filling substances has been reawakened. This is partly because the
      upper third of the face can now be successfully treated as a result of the
      development and recent US FDA approval of botulinum toxin (Botox). Patients
      seeking cosmetic improvement need no longer resort to invasive procedures that
      require down-time for the upper third of the face, and they are consequently
      seeking similar results for the lower two-thirds of the face. Filling agents have
      filled this void. This article discusses current techniques for soft tissue
      augmentation, including fat transfer and bovine collagen injections, which enable
      doctors to provide their patients with highly satisfactory results using
      minimally invasive procedures. Included in this review are an overview of the
      history of soft tissue augmentation and a brief prospectus of where this field of
      dermatology is headed in the future. Many of the currently available fillers are
      listed with a description of their most popular uses, possible adverse effects,
      manufacturers, and countries of use. Information regarding injection techniques
      and results from the most recent studies help to make this paper a useful source
      of information for experienced and novice injectors alike.

PMID- 16605292
TI  - Safety, efficacy, and dosage of 1% pimecrolimus cream for the treatment of atopic
      dermatitis in daily practice.
AB  - INTRODUCTION: Although several controlled clinical trials have demonstrated the
      efficacy and good tolerability of 1% pimecrolimus cream for the treatment of
      atopic dermatitis, the results of these trials may not apply to real-life usage.
      The objective of this study was to evaluate the safety and efficacy of a
      pimecrolimus-based regimen in daily practice. METHODS: This was a 6-month, open
      label, multicenter study in 947 patients aged >or=3 months with atopic dermatitis
      of all severities. The investigators incorporated 1% pimecrolimus cream into
      patients' standard treatment protocols on the basis of their clinical diagnosis.
      Use of topical corticosteroids was allowed at the discretion of the physician.
      Safety and tolerability were evaluated by monitoring adverse events. Efficacy was
      evaluated by recording changes in the Investigators' Global Assessment scores and
      pruritus scores at each visit. RESULTS: No clinically unexpected adverse events
      were reported. The discontinuation rate for adverse events was 2.3%. The disease
      improvement rate was 53.7% at week 1 and 66.9% at week 24. The pimecrolimus-based
      regimen was particularly effective for the treatment of lesions involving the
      face (improvement rate: 61.9% at week 1 and 76.7% at week 24). The greatest
      therapeutic response was experienced by pediatric patients with mild or moderate
      disease. Nonetheless, 64% and 65% of infants and children, respectively, with
      severe/very severe facial disease at baseline were clear/almost clear of signs of
      atopic dermatitis on their face at week 24. In patients aged <18 years, most of
      the improvement occurred within the first week of treatment, while in adults a
      progressive improvement was observed over the entire study period. Worsening of
      disease by the end of the study occurred in 9.5% of patients and was most
      frequent in adults (12.6%). The discontinuation rate for unsatisfactory
      therapeutic effect was 4.8%. The mean number of treatment days was 135.6 (SD
      53.2). The mean drug consumption (non-US centers only) was 4.2 g per treatment
      day. Drug consumption decreased over time as disease improved. In total, 47% of
      patients who completed the study never used topical corticosteroids over 6
      months. CONCLUSION: In daily practice, incorporation of 1% pimecrolimus cream
      into patients' standard treatment regimen is well tolerated and improves atopic
      dermatitis in approximately two-thirds of patients. Disease improvement is
      particularly evident on the face. The greatest therapeutic response is
      experienced by pediatric patients with mild or moderate disease. In these
      patients, most of the improvement is observed within 1 week from the start of
      treatment.

PMID- 16605293
TI  - Cost effectiveness of management of mild-to-moderate atopic dermatitis with 1%
      pimecrolimus cream in children and adolescents 2-17 years of age.
AB  - INTRODUCTION: Atopic dermatitis (AD) has the potential to cause a long-term
      economic impact on patients, their families, and the healthcare system.
      OBJECTIVE: To determine if 1% pimecrolimus cream is cost-effective in treating
      mild-to-moderate AD in patients 2-17 years of age. METHODS: Data on the efficacy
      of AD management with 1% pimecrolimus cream (Elidel, Novartis Pharma GmbH, Wehr,
      Germany) were obtained from a 12-month, randomized, double-blind, multinational,
      controlled clinical trial comparing pimecrolimus and conventional therapy. Markov
      modeling was used for the economic model, based on: (i) Investigator's Global
      Assessment scores assessed at each visit during the clinical trial; (ii)
      estimated costs for medication and physician visits for each level of disease
      severity; and (iii) utility values for each level of disease severity. The
      perspective was that of a third-party payer. RESULTS: In 2004 US dollars, the
      incremental cost-effectiveness of 1% pimecrolimus cream was 38,231 US dollars per
      quality-adjusted life year (QALY) gained compared with conventional therapy.
      Sensitivity analyses showed a range of 27,299 US dollarsto 63,457 US dollars per
      QALY gained. CONCLUSION: With an incremental cost-effectiveness ratio of <50,000
      US dollars per QALY gained, 1% pimecrolimus cream offers a cost-effective
      therapeutic option in the management of AD.

PMID- 16605294
TI  - Rosacea fulminans in pregnancy: case report and review of the literature.
AB  - Rosacea fulminans is a rare disease of unknown cause which occurs exclusively in
      women years after adolescence. Although the etiology is unknown, immunologic,
      hormonal, and vascular factors have been suggested. When rosacea fulminans occurs
      during pregnancy and in women taking oral contraceptive pills, hormonal factors
      may be a trigger. Rosacea fulminans is localized specifically to the face, with
      the chin, cheeks, and forehead bearing the brunt of the attack. A dull red,
      cyanotic erythema of all involved facial areas, extending beyond the inflammatory
      nodules, is typical. We present the case of a 31-year-old pregnant woman who had
      rosacea fulminans during the first trimester of her second pregnancy. She had
      multiple erythematous papules, pustules, nodules, and purulent discharging cysts
      on the face. Conventional therapeutic approaches with systemic corticosteroids
      were associated with clear improvement within 2 months, and subsequently only
      0.75% metronidazole topical cream was used during the second trimester.

PMID- 16605295
TI  - Don't let transitional care fall through the cracks.

PMID- 16605296
TI  - Destroyed toenail with ill-defined crusted plaque.

PMID- 16605297
TI  - Partial remission. A common outcome in older adults treated for major depression.
AB  - Major depression can affect up to 10% of older adults in clinical samples.
      Longitudinal studies of older adults with major depression report that a
      significant proportion of patients do not fully recover. Partial remission or
      symptoms of major depression that do not meet criteria for major depression, is
      predicted by 1) clinical factors, such higher number of symptoms at diagnosis,
      presence of comorbid dysthymia, and health problems; 2) social variables, such as
      high levels of perceived stress and low levels of perceived social support; and
      3) perceived health/well-being variables, such as limitations in mobility or
      instrumental activities of daily living, poorer self-perceived health, finding
      life not satisfying, and looking back over life and finding it unhappy. Treatment
      options include antidepressants (alone or in combination) and psychotherapy.

PMID- 16605298
TI  - Health promotion in older adults. Promoting successful aging in primary care
      settings.
AB  - The ultimate objective of the successful aging paradigm is to improve the quality
      of life among the elderly. Although the aging process is currently immutable,
      primary care providers can modify the pathology and mitigate the expression of
      disease through prevention and treatment. Avoiding disease and disability,
      maintaining mental function and maintaining physical function are cornerstones of
      this approach. Recommendations about eating right, eating less, and exercising
      more are to make , but they are not easy to adopt for geriatric patients. Our
      elderly patients need far more physician mentoring and guidance in order to
      attain the goal of a healthier and higher quality of life that is implied by
      strategies for successful aging.

PMID- 16605299
TI  - Hypopituitarism in older adults. The report of five cases with different
      presentations.
AB  - Patients with hypopituitarism may present with myriad signs and symptoms which
      result from reduced secretion of one or more pituitary hormones. Severe
      hyponatremia and hypoglycemia are rare, but potentially life threatening
      presenting clinical features of hypopituitarism. As these abnormalities are
      completely restored with replacement therapy and patients are often undiagnosed
      until admission, a high clinical suspicion is necessary to diagnose a patient
      with hypopituitarism. We present five cases, each exhibiting rare symptoms of
      hypopituitarism--severe hyponatremia, hypoglycemia and osteoporosis--as the only
      presenting feature; these cases illustrate that hypopituitarism must be
      considered in the differential diagnosis of these abnormalities, especially in
      older patients.

PMID- 16605300
TI  - The effect of alpha+-thalassaemia on the incidence of malaria and other diseases
      in children living on the coast of Kenya.
AB  - BACKGROUND: The alpha-thalassaemias are the commonest genetic disorders of
      humans. It is generally believed that this high frequency reflects selection
      through a survival advantage against death from malaria; nevertheless, the
      epidemiological description of the relationships between alpha-thalassaemia,
      malaria, and other common causes of child mortality remains incomplete. METHODS
      AND FINDINGS: We studied the alpha+-thalassaemia-specific incidence of malaria
      and other common childhood diseases in two cohorts of children living on the
      coast of Kenya. We found no associations between alpha+-thalassaemia and the
      prevalence of symptomless Plasmodium falciparum parasitaemia, the incidence of
      uncomplicated P. falciparum disease, or parasite densities during mild or severe
      malaria episodes. However, we found significant negative associations between
      alpha+-thalassaemia and the incidence rates of severe malaria and severe anaemia
      (haemoglobin concentration < 50 g/l). The strongest associations were for severe
      malaria anaemia (> 10,000 P. falciparum parasites/mul) and severe nonmalaria
      anaemia; the incidence rate ratios and 95% confidence intervals (CIs) for alpha+
      thalassaemia heterozygotes and homozygotes combined compared to normal children
      were, for severe malaria anaemia, 0.33 (95% CI, 0.15,0.73; p = 0.006), and for
      severe nonmalaria anaemia, 0.26 (95% CI, 0.09,0.77; p = 0.015). CONCLUSIONS: Our
      observations suggest, first that selection for alpha+-thalassaemia might be
      mediated by a specific effect against severe anaemia, an observation that may
      lead to fresh insights into the aetiology of this important condition. Second,
      although alpha+-thalassaemia is strongly protective against severe and fatal
      malaria, its effects are not detectable at the level of any other malaria
      outcome; this result provides a cautionary example for studies aimed at testing
      malaria interventions or identifying new malaria-protective genes.

PMID- 16605301
TI  - Unresponsiveness to Glucantime treatment in Iranian cutaneous leishmaniasis due
      to drug-resistant Leishmania tropica parasites.
AB  - BACKGROUND: Recent circumstantial evidence suggests that an increasing number of
      Iranian patients with cutaneous leishmaniasis are unresponsive to meglumine
      antimoniate (Glucantime), the first line of treatment in Iran. This study was
      designed to determine whether the clinical responses (healing, or non-healing)
      were correlated with the susceptibility of Leishmania parasites to Glucantime.
      METHODS AND FINDINGS: In vitro susceptibility testing was first performed on 185
      isolated parasites in the intracellular mouse peritoneal macrophage model. A
      strong correlation between the clinical outcome and the in vitro effective
      concentration 50% (EC50) values was observed. Parasites derived from patients
      with non-healing lesions had EC50 values at least 4-fold higher than parasites
      derived from lesions of healing patients. A selection of these strains was typed
      at the molecular level by pulsed-field gels and by sequencing the pteridine
      reductase 1 (PTR1) gene. These techniques indicated that 28 out of 31 selected
      strains were Leishmania tropica and that three were Leishmania major. The L.
      major isolates were part of a distinct pulsed-field group, and the L. tropica
      isolates could be classified in three related additional pulsed-field groups. For
      each pulsed-field karyotype, we selected sensitive and resistant parasites in
      which we transfected the firefly luciferase marker to assess further the in vitro
      susceptibility of field isolates in the monocyte cell line THP1. These
      determinations confirmed unequivocally that patients with non-healing lesions
      were infected with L. tropica parasites resistant to Glucantime. Additional
      characterization of the resistant isolates showed that resistance is stable and
      can be reversed by buthionine sulfoximine, an inhibitor of glutathione
      biosynthesis. CONCLUSIONS: To the authors' knowledge, this is the first report of
      proven resistant parasites contributing to treatment failure for cutaneous
      leishmaniasis and shows that primary Glucantime-resistant L. tropica field
      isolates are now frequent in Iran.

PMID- 16605302
TI  - Cynomolgus macaque as an animal model for severe acute respiratory syndrome.
AB  - BACKGROUND: The emergence of severe acute respiratory syndrome (SARS) in 2002 and
      2003 affected global health and caused major economic disruption. Adequate animal
      models are required to study the underlying pathogenesis of SARS-associated
      coronavirus (SARS-CoV) infection and to develop effective vaccines and
      therapeutics. We report the first findings of measurable clinical disease in
      nonhuman primates (NHPs) infected with SARS-CoV. METHODS AND FINDINGS: In order
      to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we
      infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected
      in the nares and bronchus, group II in the nares and conjunctiva, and group III
      intravenously. Nonhuman primates in groups I and II developed mild to moderate
      symptomatic illness. All NHPs demonstrated evidence of viral replication and
      developed neutralizing antibodies. Chest radiographs from several animals in
      groups I and II revealed unifocal or multifocal pneumonia that peaked between
      days 8 and 10 postinfection. Clinical laboratory tests were not significantly
      changed. Overall, inoculation by a mucosal route produced more prominent disease
      than did intravenous inoculation. Half of the group I animals were infected with
      a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain.
      This infectious clone produced disease indistinguishable from wild-type Urbani
      strain. CONCLUSIONS: SARS-CoV infection of cynomolgus macaques did not reproduce
      the severe illness seen in the majority of adult human cases of SARS; however,
      our results suggest similarities to the milder syndrome of SARS-CoV infection
      characteristically seen in young children.

PMID- 16605303
TI  - Echolocating bats use a nearly time-optimal strategy to intercept prey.
AB  - Acquisition of food in many animal species depends on the pursuit and capture of
      moving prey. Among modern humans, the pursuit and interception of moving targets
      plays a central role in a variety of sports, such as tennis, football, Frisbee,
      and baseball. Studies of target pursuit in animals, ranging from dragonflies to
      fish and dogs to humans, have suggested that they all use a constant bearing (CB)
      strategy to pursue prey or other moving targets. CB is best known as the
      interception strategy employed by baseball outfielders to catch ballistic fly
      balls. CB is a time-optimal solution to catch targets moving along a straight
      line, or in a predictable fashion--such as a ballistic baseball, or a piece of
      food sinking in water. Many animals, however, have to capture prey that may make
      evasive and unpredictable maneuvers. Is CB an optimum solution to pursuing
      erratically moving targets? Do animals faced with such erratic prey also use CB?
      In this paper, we address these questions by studying prey capture in an
      insectivorous echolocating bat. Echolocating bats rely on sonar to pursue and
      capture flying insects. The bat's prey may emerge from foliage for a brief time,
      fly in erratic three-dimensional paths before returning to cover. Bats typically
      take less than one second to detect, localize and capture such insects. We used
      high speed stereo infra-red videography to study the three dimensional flight
      paths of the big brown bat, Eptesicus fuscus, as it chased erratically moving
      insects in a dark laboratory flight room. We quantified the bat's complex pursuit
      trajectories using a simple delay differential equation. Our analysis of the
      pursuit trajectories suggests that bats use a constant absolute target direction
      strategy during pursuit. We show mathematically that, unlike CB, this approach
      minimizes the time it takes for a pursuer to intercept an unpredictably moving
      target. Interestingly, the bat's behavior is similar to the interception strategy
      implemented in some guided missiles. We suggest that the time-optimal strategy
      adopted by the bat is in response to the evolutionary pressures of having to
      capture erratic and fast moving insects.

PMID- 16605305
TI  - Scientific illiteracy and the partisan takeover of biology.

PMID- 16605304
TI  - Parallel thalamic pathways for whisking and touch signals in the rat.
AB  - In active sensation, sensory information is acquired via movements of sensory
      organs; rats move their whiskers repetitively to scan the environment, thus
      detecting, localizing, and identifying objects. Sensory information, in turn,
      affects future motor movements. How this motor-sensory-motor functional loop is
      implemented across anatomical loops of the whisker system is not yet known. While
      inducing artificial whisking in anesthetized rats, we recorded the activity of
      individual neurons from three thalamic nuclei of the whisker system, each
      belonging to a different major afferent pathway: paralemniscal, extralemniscal (a
      recently discovered pathway), or lemniscal. We found that different sensory
      signals related to active touch are conveyed separately via the thalamus by these
      three parallel afferent pathways. The paralemniscal pathway conveys sensor motion
      (whisking) signals, the extralemniscal conveys contact (touch) signals, and the
      lemniscal pathway conveys combined whisking-touch signals. This functional
      segregation of anatomical pathways raises the possibility that different sensory
      motor processes, such as those related to motion control, object localization,
      and object identification, are implemented along different motor-sensory-motor
      loops.

PMID- 16605306
TI  - A model of the ventral visual system based on temporal stability and local
      memory.
AB  - The cerebral cortex is a remarkably homogeneous structure suggesting a rather
      generic computational machinery. Indeed, under a variety of conditions, functions
      attributed to specialized areas can be supported by other regions. However, a
      host of studies have laid out an ever more detailed map of functional cortical
      areas. This leaves us with the puzzle of whether different cortical areas are
      intrinsically specialized, or whether they differ mostly by their position in the
      processing hierarchy and their inputs but apply the same computational
      principles. Here we show that the computational principle of optimal stability of
      sensory representations combined with local memory gives rise to a hierarchy of
      processing stages resembling the ventral visual pathway when it is exposed to
      continuous natural stimuli. Early processing stages show receptive fields similar
      to those observed in the primary visual cortex. Subsequent stages are selective
      for increasingly complex configurations of local features, as observed in higher
      visual areas. The last stage of the model displays place fields as observed in
      entorhinal cortex and hippocampus. The results suggest that functionally
      heterogeneous cortical areas can be generated by only a few computational
      principles and highlight the importance of the variability of the input signals
      in forming functional specialization.

PMID- 16605308
TI  - Development projects to improve maternal and child health: assessing the impact.

PMID- 16605309
TI  - Protection against prenatal alcohol-induced damage.

PMID- 16605307
TI  - Neocortical connectivity during episodic memory formation.
AB  - During the formation of new episodic memories, a rich array of perceptual
      information is bound together for long-term storage. However, the brain
      mechanisms by which sensory representations (such as colors, objects, or
      individuals) are selected for episodic encoding are currently unknown. We
      describe a functional magnetic resonance imaging experiment in which participants
      encoded the association between two classes of visual stimuli that elicit
      selective responses in the extrastriate visual cortex (faces and houses). Using
      connectivity analyses, we show that correlation in the hemodynamic signal between
      face- and place-sensitive voxels and the left dorsolateral prefrontal cortex is a
      reliable predictor of successful face-house binding. These data support the view
      that during episodic encoding, "top-down" control signals originating in the
      prefrontal cortex help determine which perceptual information is fated to be
      bound into the new episodic memory trace.

PMID- 16605310
TI  - Current and universal scaling in anomalous transport.
AB  - Anomalous transport in tilted periodic potentials is investigated within the
      framework of the fractional Fokker-Planck dynamics and the underlying continuous
      time random walk. The analytical solution for the stationary, anomalous current
      is obtained in closed form. We derive a universal scaling law for anomalous
      diffusion occurring in tilted periodic potentials. This scaling relation is
      corroborated with precise numerical studies covering wide parameter regimes and
      different shapes for the periodic potential, being either symmetric or
      ratchetlike.

PMID- 16605311
TI  - Solvation forces between colloidal nanoparticles: directed alignment.
AB  - We study the solvation forces between colloidal nanoparticles in Lennard-Jones
      liquids using molecular-dynamics simulations. We find that due to the interplay
      between solvent ordering and surface structure, the solvation forces between two
      nanoparticles can vary between attraction and repulsion as the particles are
      rotated relative to one another at a fixed separation. These solvent-mediated
      forces tend to align the nanoparticles so that they rotate to approach one
      another in a solution via preferred pathways. This directed alignment could play
      a role in the assembly of macromolecules and nanoparticles in solution.

PMID- 16605312
TI  - Complex viscosity behavior and cluster formation in attractive colloidal systems.
AB  - The increase in viscosity that is observed in attractive colloidal systems by
      varying the temperature or the volume fraction can be related to the formation of
      structures due to particle aggregation. In particular we have studied the
      nontrivial dependence of the viscosity from the temperature and the volume
      fraction in the copolymer-micellar system L64. The comparison of the experimental
      data with the results of numerical simulations in a simple model for gelation
      phenomena suggests that this intriguing behavior can be explained in terms of
      cluster formation and that this picture can be quite generally extended to other
      attractive colloidal systems.

PMID- 16605313
TI  - Dynamic signature for the equilibrium percolation threshold of attractive
      colloidal fluids.
AB  - Short-time self-diffusivities, D(S)S, are computed for attractive colloidal
      fluids with van der Waals potentials to identify their percolation threshold and
      a previously unexplained dynamic transition. Our results show a discontinuous
      change in the slope of D(S)S vs temperature as the percolation threshold is
      crossed. Because D(S)S depends only on multibody hydrodynamic interactions, the
      percolation threshold of attractive colloidal fluids is shown to correspond to a
      transition in a dynamic property consistent with the linear viscoelastic
      measurements of Woutersen et al., J. Chem. Phys. 101, 542 (1994).

PMID- 16605314
TI  - Critical behavior of the specific heat in glass formers.
AB  - We show numeric evidence that, at low enough temperatures, the potential energy
      density of a glass-forming liquid fluctuates over length scales much larger than
      the interaction range. We focus on the behavior of translationally invariant
      quantities. The growing correlation length is unveiled by studying the finite
      size effects. In the thermodynamic limit, the specific heat and the relaxation
      time diverge as a power law. Both features point towards the existence of a
      critical point in the metastable supercooled liquid phase.

PMID- 16605315
TI  - Predicting nonpolymeric materials structure with real-space self-consistent field
      theory.
AB  - Polymer self-consistent field theory of the Edwards-Helfand kind is the state-of
      the-art method for predicting the morphologies of block copolymer materials. The
      methodology of block copolymer self-consistent field theory is transported to
      classical density functional theory such that a wide range of self-consistent
      field theory tools can be applied to completely nonpolymeric materials, such as
      liquid crystal, molecular, or colloidal systems. This allows for the prediction
      of structure in nonpolymeric condensed matter systems without any prior knowledge
      of the possible phases, using calculations that take a fraction of the time
      needed for simulations. The approach is applied to a simple interaction site
      density functional theory representing adsorbed nitrogen molecules, and plastic
      crystal as well as herringbone phases are found in the phase diagram.

PMID- 16605316
TI  - Dynamical perspective of the freezing transition of a suspension of hard spheres
      from the velocity autocorrelation function.
AB  - The velocity autocorrelation function of concentrated colloidal fluids of hard
      sphere particles, measured by dynamic light scattering, decays to the
      experimental noise floor from below. The decay follows a stretched exponential
      function of delay time for the colloidal fluid in thermodynamic equilibrium, and
      a power law for the nonequilibrium, undercooled colloidal fluid. Consideration of
      this difference between the two states points to a possible dynamical mechanism
      of freezing.

PMID- 16605317
TI  - Spatially resolved small-angle neutron scattering in the 1-2 plane: a study of
      shear-induced phase-separating wormlike micelles.
AB  - The shear-induced microstructure of a shear-induced phase separating (SIPS)
      wormlike micellar solution is measured by combining small-angle neutron
      scattering with a shear cell capable of gap-resolved measurement in the 1-2
      (velocity-velocity gradient) plane. Quantitative results show evidence for shear
      induced microphase separation accompanied by shear banding. The results suggest
      both concentration fluctuations and gradients in segmental alignment occurring
      during SIPS.

PMID- 16605318
TI  - Colloidal interactions in nematic fluids.
AB  - Microscopic theory is used to obtain effective interactions between colloidal
      particles in nematic fluids subjected to an external orienting field. It is shown
      that the field can dramatically change the effective intercolloidal interactions
      without altering the symmetry of the director configuration around a single
      particle. Our calculations suggest that a rich variety of colloidal structures
      can be promoted by varying the external field.

PMID- 16605319
TI  - Orientational ordering of solutes in confined nematic solvents: a possible way to
      probe director distributions.
AB  - We propose a method to study the director distribution in a nematic liquid
      crystal confined in a slab geometry. It is based on the measurement, by NMR
      spectroscopy, of the Saupe ordering matrices of a collection of biaxial solute
      molecules dissolved in the confined nematic liquid crystal of interest. Due to
      the combined action of the surface anchoring and magnetic field interactions, the
      director is generally not uniformly aligned within the cell. Consequently, the
      resulting Saupe ordering matrices may be considered as weighted sums of the
      corresponding Saupe ordering matrices measured in the bulk nematic phase, and
      modulated by the director distribution. The determined Saupe ordering matrices
      may then be taken as the set of data in a fitting process where the fitting
      function, whose form is deduced from molecular mean field and continuum theories,
      is dependent on the director distribution; the angle that the director forms with
      the plain surfaces and the corresponding derivative at the surfaces are taken as
      fitting parameters. The methodology is preliminarily tested on the virtual
      nematic phase formed by the Lebwohl-Lasher lattice model, confined between two
      plain surfaces favoring planar anchoring, and where a number of model cuboidal
      solutes has been dissolved. We comment on the implemention of the method when
      applied to real experimental systems.

PMID- 16605320
TI  - Substrate specificity of peptide adsorption: a model study.
AB  - Applying the contact density chain-growth algorithm to lattice heteropolymers, we
      identify the conformational transitions of a nongrafted hydrophobic-polar
      heteropolymer with 103 residues in the vicinity of a polar, a hydrophobic, and a
      uniformly attractive substrate. Introducing only two system parameters, the
      numbers of surface contacts and intrinsic hydrophobic contacts, respectively, we
      obtain surprisingly complex temperature and solvent dependent, substrate-specific
      pseudophase diagrams.

PMID- 16605321
TI  - Stochastic models for tumoral growth.
AB  - Strong experimental evidence has indicated that tumor growth belongs to the
      molecular beam epitaxy universality class. This type of growth is characterized
      by the constraint of cell proliferation to the tumor border and the surface
      diffusion of cells at the growing edge. Tumor growth is thus conceived as a
      competition for space between the tumor and the host, and cell diffusion at the
      tumor border is an optimal strategy adopted for minimizing the pressure and
      helping tumor development. Two stochastic partial differential equations are
      reported in this paper in order to correctly model the physical properties of
      tumoral growth in (1 + 1) and (2 + 1) dimensions. The advantage of these models
      is that they reproduce the correct geometry of the tumor and are defined in terms
      of polar variables. An analysis of these models allows us to quantitatively
      estimate the response of the tumor to an unfavorable perturbation during growth.

PMID- 16605322
TI  - Long-range interactions and evolutionary stability in a predator-prey system.
AB  - Evolving ecosystems often are dominated by spatially local dynamics, but many
      also include long-range transport that mixes spatially separated groups. The
      existence of such mixing may be of critical importance since research shows
      spatial separation may be responsible for long-term stability of predator-prey
      systems. Complete mixing results in rapid global extinction, while spatial
      systems achive long term stability due to an inhomogeneous spatial pattern of
      local extinctions. We consider the robustness of a generic evolving predator-prey
      or host-pathogen model to long-range mixing and find a transition to global
      extinction at nontrivial values implying that even if significant mixing already
      exists, a small amount of additional mixing may cause extinction. Our results are
      relevant to the global mixing of species due to human intervention and to global
      transport of infectious disease.

PMID- 16605323
TI  - Ghost stochastic resonance with distributed inputs in pulse-coupled electronic
      neurons.
AB  - We study experimentally the phenomenon of ghost stochastic resonance in pulse
      coupled excitable systems, for input signals distributed among different
      elements. Specifically, two excitable electronic circuits are driven by different
      sinusoidal signals that produce periodic spikes at distinct frequencies. Their
      outputs are sent to a third circuit that processes these spiking signals and is
      additionally perturbed by noise. When the input signals are harmonics of a
      certain fundamental (that is not present in the inputs) the processing circuit
      exhibits, for an optimal amount of noise, a resonant response at the frequency of
      the missing fundamental (ghost frequency). In contrast with the standard case in
      which the signals being directly integrated are sinusoidal, this behavior relies
      here on a coincidence-detection mechanism. When the input signals are
      homogeneously shifted in frequency, the processing circuit responds with pulse
      packages composed of spikes at a frequency that depends linearly on the frequency
      shift. Expressions for the dependence of the package period and duration on the
      frequency shift and spike width, respectively, are obtained. These results
      provide an experimental verification of a recently proposed mechanism of binaural
      pitch perception.

PMID- 16605324
TI  - Achieving optimal rectification using underdamped rocked ratchets.
AB  - An underdamped rocked ratchet operated at very low temperatures and damping is
      shown: (i) to be capable of rectifying the ac input signal more efficiently than
      in the overdamped regime; (ii) to be insensitive to the initial conditions, at
      variance with noiseless, or deterministic, ratchets; and (iii) to be
      characterized by a wide damping "window," where its efficiency is appreciable
      also for weak input amplitudes. All these properties are rather robust,
      irrespective of the wave form of the drive and the ratchet potential. Our results
      relate to recent experiments on current-biased annular Josephson junctions and
      also on rectifiers of magnetic flux quanta in superconductors.

PMID- 16605325
TI  - Mathematical basis for a general theory of Laplacian transport towards irregular
      interfaces.
AB  - The theory of Laplacian transport towards and across irregular surfaces is
      reformulated in terms of the Dirichlet-to-Neumann operator and its spectral
      characteristics. This permits us to obtain an exact equivalent circuit for the
      impedance of a working interface of arbitrary shape. The important result is that
      only very few eigenmodes of this operator do govern the entire response of a
      macroscopic system. This property drastically simplifies the understanding of
      irregular or prefractal interfaces. The results can be applied in
      electrochemistry, physiology and chemical engineering, fields where exchange
      processes across surfaces with complex geometry are ubiquitous.

PMID- 16605326
TI  - Space-fractional advection-diffusion and reflective boundary condition.
AB  - Anomalous diffusive transport arises in a large diversity of disordered media.
      Stochastic formulations in terms of continuous time random walks (CTRWs) with
      transition probability densities showing space- and/or time-diverging moments
      were developed to account for anomalous behaviors. A broad class of CTRWs was
      shown to correspond, on the macroscopic scale, to advection-diffusion equations
      involving derivatives of noninteger order. In particular, CTRWs with Levy
      distribution of jumps and finite mean waiting time lead to a space-fractional
      equation that accounts for superdiffusion and involves a nonlocal integral
      differential operator. Within this framework, we analyze the evolution of
      particles performing symmetric Levy flights with respect to a fluid moving at
      uniform speed . The particles are restricted to a semi-infinite domain limited by
      a reflective barrier. We show that the introduction of the boundary condition
      induces a modification in the kernel of the nonlocal operator. Thus, the
      macroscopic space-fractional advection-diffusion equation obtained is different
      from that in an infinite medium.

PMID- 16605327
TI  - Linear stability of the cylindrical Couette flow of a rarefied gas.
AB  - A rarefied gas between two coaxial circular cylinders of infinite length,
      rotating with different angular velocities and kept at a common temperature, is
      considered. The stability of the circumferentially as well as axially uniform
      flow (cylindrical Couette flow) for circumferentially uniform small disturbances
      is investigated on the basis of kinetic theory. The linear-stability analysis is
      performed using the Bhatnagar-Gross-Krook model of the Boltzmann equation and the
      diffuse reflection condition on the cylinders. The maximum growth rate of the
      disturbances is determined numerically by solving the initial and boundary value
      problem for the disturbances for relatively small Knudsen numbers and wide ranges
      of angular velocities of the cylinders. As a result, the parameter range where
      the cylindrical Couette flow is unstable is clarified. The result is compared
      with the corresponding result based on the continuum model of the compressible
      Navier-Stokes type. A comparison is also made with the result of a direct
      numerical analysis of the original Boltzmann system, obtained by the direct
      simulation Monte Carlo method in previous papers as well as in the present study.

PMID- 16605328
TI  - Fluctuating magnetic moments in liquid metals.
AB  - We reanalyze literature data on neutron scattering by liquid metals and show that
      there is an additional broad (in energy) quasielastic mode present that is absent
      in x-ray scattering. This mode cannot be accounted for by the standard coherent
      and incoherent scattering mechanisms. We argue that this mode indicates that
      nonmagnetic liquid metals possess a magnetic moment which fluctuates on a
      picosecond time scale. This time scale is the same as the time scale of the cage
      diffusion process in which an ion rattles around in the cage formed by its
      neighbors. We find that these fluctuating magnetic moments are present in liquid
      Hg, Al, Ga, and Pb and possibly also in the alkali metals.

PMID- 16605329
TI  - Dynamics of a tracer granular particle as a nonequilibrium Markov process.
AB  - The dynamics of a tracer particle in a stationary driven granular gas is
      investigated. We show how to transform the linear Boltzmann equation, describing
      the dynamics of the tracer into a master equation for a continuous Markov
      process. The transition rates depend on the stationary velocity distribution of
      the gas. When the gas has a Gaussian velocity probability distribution function
      (PDF), the stationary velocity PDF of the tracer is Gaussian with a lower
      temperature and satisfies detailed balance for any value of the restitution
      coefficient alpha. As soon as the velocity PDF of the gas departs from the
      Gaussian form, detailed balance is violated. This nonequilibrium state can be
      characterized in terms of a Lebowitz-Spohn action functional W(tau) defined over
      trajectories of time duration tau. We discuss the properties of this functional
      and of a similar functional W(tau), which differs from the first for a term that
      is nonextensive in time. On the one hand, we show that in numerical experiments
      (i.e., at finite times tau), the two functionals have different fluctuations and
      W always satisfies an Evans-Searles-like symmetry. On the other hand, we cannot
      observe the verification of the Lebowitz-Spohn-Gallavotti-Cohen (LS-GC) relation,
      which is expected for W(tau) at very large times tau. We give an argument for the
      possible failure of the LS-GC relation in this situation. We also suggest
      practical recipes for measuring W(tau) and W(tau) in experiments.

PMID- 16605330
TI  - Chapman-Enskog expansion about nonequilibrium states with application to the
      sheared granular fluid.
AB  - The Chapman-Enskog method of solution of kinetic equations, such as the Boltzmann
      equation, is based on an expansion in gradients of the deviations of the
      hydrodynamic fields from a uniform reference state (e.g., local equilibrium).
      This paper presents an extension of the method so as to allow for expansions
      about arbitrary, far-from-equilibrium reference states. The primary result is a
      set of hydrodynamic equations for studying variations from the arbitrary
      reference state which, unlike the usual Navier-Stokes hydrodynamics, does not
      restrict the reference state in any way. The method is illustrated by application
      to a sheared granular gas which cannot be studied using the usual Navier-Stokes
      hydrodynamics.

PMID- 16605331
TI  - Probability distribution of residence times of grains in models of rice piles.
AB  - We study the probability distribution of residence time of a grain at a site, and
      its total residence time inside a pile, in different rice pile models. The tails
      of these distributions are dominated by the grains that get deeply buried in the
      pile. We show that, for a pile of size L, the probabilities that the residence
      time at a site or the total residence time is greater than t, both decay as
      1/t(ln t)x for L(omega) << t << exp(L(gamma)) where gamma is an exponent > or =
      1, and values of x and omega in the two cases are different. In the Oslo rice
      pile model we find that the probability of the residence time T(i) at a site i
      being greater than or equal to t is a nonmonotonic function of L for a fixed t
      and does not obey simple scaling. For model in d dimensions, we show that the
      probability of minimum slope configuration in the steady state, for large L,
      varies as exp(-kappaL(d+2)) where kappa is a constant, and hence gamma=d+2.

PMID- 16605332
TI  - Transport coefficients for an inelastic gas around uniform shear flow: linear
      stability analysis.
AB  - The inelastic Boltzmann equation for a granular gas is applied to spatially
      inhomogeneous states close to uniform shear flow. A normal solution is obtained
      via a Chapman-Enskog-like expansion around a local shear flow distribution. The
      heat and momentum fluxes are determined to first order in the deviations of the
      hydrodynamic field gradients from their values in the reference state. The
      corresponding transport coefficients are determined from a set of coupled linear
      integral equations which are approximately solved by using a kinetic model of the
      Boltzmann equation. The main new ingredient in this expansion is that the
      reference state f(0) (zeroth-order approximation) retains all the hydrodynamic
      orders in the shear rate. In addition, since the collisional cooling cannot be
      compensated locally for viscous heating, the distribution f(0) depends on time
      through its dependence on temperature. This means that in general, for a given
      degree of inelasticity, the complete nonlinear dependence of the transport
      coefficients on the shear rate requires analysis of the unsteady hydrodynamic
      behavior. To simplify the analysis, the steady-state conditions have been
      considered here in order to perform a linear stability analysis of the
      hydrodynamic equations with respect to the uniform shear flow state. Conditions
      for instabilities at long wavelengths are identified and discussed.

PMID- 16605333
TI  - Diagram of the aging dynamics in laponite suspensions at low ionic strength.
AB  - We measure the dynamic structure factor (DSF) of probe particles embedded in an
      aging laponite suspension quenched by cessation of shear and the associated
      relaxation time tau as a function of wave vector q and aging time t(w). The
      different q dependences measured in the successive exponential and full aging
      regimes, respectively, tau approximately q(-2) and tau approximately q(-1.25),
      yield a weak positive q dependence for the aging time t(wc) corresponding to the
      crossover between the two regimes. This implies that the full aging behavior is
      first seen when investigating large length scales in the aging suspension. We
      propose a qualitative diagram of the aging dynamics and discuss the features of
      the DSF of the probes and of the matrix in the two aging regimes. Consistently
      with the idea that the full aging regime is first observed when probing large
      length scales, t(wc) is markedly shorter when the motion of the probes is tracked
      instead of the collective fluctuations of concentration in the matrix. The
      exponential aging regime is most probably related to the liquid-glass transition
      induced by the cessation of shear rather than to the aging of a glass.

PMID- 16605334
TI  - Agglomeration of oppositely charged particles in nonpolar liquids.
AB  - We study the aggregation of insulating electrically charged spheres suspended in
      a nonpolar liquid. Regarding the van der Waals interaction as an irreversible
      sticking force, we are especially interested in the charge distribution after
      aggregation. Solving the special case of two oppositely charged particles
      exactly, it is shown that the surface charges either recombine or form a residual
      dipole, depending on the initial condition. The theoretical findings are compared
      to numerical results from Monte Carlo simulations.

PMID- 16605335
TI  - Volume terms for charged colloids: a grand-canonical treatment.
AB  - We present a study of thermodynamic properties of suspensions of charged colloids
      on the basis of linear Poisson-Boltzmann theory. We calculate the effective
      Hamiltonian of the colloids by integrating out the ionic degrees of freedom grand
      canonically. This procedure not only yields the well-known pairwise screened
      Coulomb interaction between the colloids, but also additional volume terms that
      affect the phase behavior and the thermodynamic properties, such as the osmotic
      pressure. These calculations are greatly facilitated by the grand-canonical
      character of our treatment of the ions and allow for relatively fast computations
      compared to earlier studies in the canonical ensemble. Moreover, the present
      derivation of the volume terms are relatively simple, make a direct connection
      with Donnan equilibrium, yield an explicit expression for the effective screening
      constant, and allow for extensions to include, for instance, nonlinear effects.

PMID- 16605336
TI  - Segregation in multicomponent ceramic colloids during drying of droplets.
AB  - Studies of drying of colloidal droplets focus on unary particle systems. We
      report here the drying of binary and ternary powder suspensions. When
      multicomponent ceramic suspensions are deposited in the form of small drops (5
      microl), particle segregation can occur on drying so that the upper surface of
      the powder residue does not match that of the bulk composition. We show that the
      segregation effect and the shape of the droplet residues are both related to the
      participation of particles in two types of flow during drying; radial flow toward
      the rim where the three-phase boundary becomes locked by a pile up of particles
      and secondly, recirculation flows in the remaining liquid driven by Marangoni
      stresses. Methods to control both shape and segregation are described. The
      phenomenon described is general and independent of the method of preparing the
      drops but the motivation is to obtain uniform drop shape and composition in thick
      film ceramic libraries in combinatorial ink-jet printing.

PMID- 16605337
TI  - Interaction between two inhomogeneously charged parallel surfaces in the strong
      coupling regime.
AB  - The counterion density profile and pressure between two inhomogenously charged
      parallel plates are analyzed analytically and numerically in the strong-coupling
      regime. Point charges are used and the surface charges are immobile. It is found
      that when the surface charge distribution is inhomogeneous, the charge coupling
      effect becomes stronger, the counterion spatial distribution is more localized
      toward the plate surfaces, and, thus, the pressure between two plates becomes
      lower than in the case when the surface charge distribution is homogeneous.

PMID- 16605339
TI  - Structure of an amphiphilic lattice gas, and its relationship to microclustering
      of methanol in water.
AB  - We present a lattice gas model to show that a system of amphiphilic molecules in
      solution forms clusters without phase separating. This is designed to be the
      simplest possible model that captures the essence of the so-called
      microclustering observed both experimentally and by molecular-dynamics computer
      simulation of methanol in water. The Hamiltonian contains no adjustable
      parameters, yet exhibits surprisingly complex behavior as a function of
      temperature and concentration. By studying the specific heat, we reveal three
      phase boundaries-between a low-temperature phase comprising straight bilayers,
      intermediate phases exhibiting twisted bilayer and clustering, and a high
      temperature phase, which is essentially gas-like. None of the observed phases
      correspond to the crystalization or phase separation expected of a simple
      mixture; instead, they correspond to loss of different types of entropy.

PMID- 16605338
TI  - Shear-induced discontinuous and continuous topological transitions in a
      hyperswollen membrane system.
AB  - Here we demonstrate that both discontinuous and continuous transition between the
      sponge and lamellar phase can be induced by steady shear flow for a hyperswollen
      membrane system. The discontinuous nature of the transition is revealed by a
      distinct hysteresis in the rheological behavior between shear-rate increasing and
      decreasing measurements at a constant temperature. This discontinuity becomes
      weaker with an increase in the shear rate and temperature, and the transition
      eventually becomes a continuous one without any hysteresis. We also found another
      shear-induced transition in a one-phase lamellar region. The dynamic phase
      diagram in a nonequilibrium steady state under shear is constructed for the
      sponge-lamellar transition as well as another transition in a stable lamellar
      phase. Possible physical mechanisms for these shear-induced transitions are
      discussed.

PMID- 16605340
TI  - Dynamics of an active magnetic particle in a rotating magnetic field.
AB  - The motion of an active (self-propelling) particle with a permanent magnetic
      moment under the action of a rotating magnetic field is considered. We show that
      below a critical frequency of the external field the trajectory of a particle is
      a circle. For frequencies slightly above the critical point the particle moves on
      an approximately circular trajectory and from time to time jumps to another
      region of space. Symmetry of the particle trajectory depends on the
      commensurability of the field period and the period of the orientational motion
      of the particle. We also show how our results can be used to study the properties
      of naturally occurring active magnetic particles, so-called magnetotactic
      bacteria.

PMID- 16605341
TI  - Ginzburg-Landau theory of solvation in polar fluids: Ion distribution around an
      interface.
AB  - We present a Ginzburg-Landau theory of solvation of ions in polar binary
      mixtures. The solvation free energy arising from the ion-dipole interaction can
      strongly depend on the composition and the ion species. Most crucial in phase
      separation is then the difference in the solvation free energy between the two
      phases, which is the origin of the Galvani potential difference known in
      electrochemistry. We also take into account an image potential acting on each
      ion, which arises from inhomogeneity in the dielectric constant and is important
      close to an interface at very small ion densities. Including these solvation and
      image interactions, we calculate the ion distributions and the electric potential
      around an interface with finite thickness. In particular, on approaching the
      critical point, the ion density difference between the two phases becomes milder.
      The critical temperature itself is much shifted even by a small amount of ions.
      We examine the surface tension in the presence of ions in various cases.

PMID- 16605342
TI  - Dynamic fluctuations of dipolar semiflexible filaments.
AB  - On the basis of the model of a flexible magnetic filament, the characteristics of
      their thermal fluctuations are considered. The crossover of the time dependence
      of the mean quadratic displacement from t(3/4) to t(1/2) at the magnetic field
      increase is found. Two characteristic mechanisms of the magnetization relaxation
      time distribution--straightening of the thermal undulations and excitation of the
      bending modes of the free ends under the action of an ac magnetic field--are
      described. In both cases, the characteristic scaling law omega(-3/4) of the
      magnetic susceptibility in a high-frequency range is found.

PMID- 16605343
TI  - Phase separation in an exactly solvable model binary solution with three-body
      interactions and intermolecular bonding.
AB  - A model is presented in which the bonds of a honeycomb lattice are covered by
      rodlike molecules of types AA and BB, molecular ends near a common site having
      both three-body interactions and orientation-dependent bonding between two A
      molecular ends and between an A and a B molecular end. Phase diagrams
      corresponding to the separation into AA-rich and BB-rich phases are calculated
      exactly. Depending on the relative strengths of the interactions, one of several
      qualitatively different types of phase diagrams can result, including diagrams
      containing phenomena such as a double critical point or two separate asymmetric
      closed loops. The model is essentially a limiting case of a previously considered
      ternary solution model, and it is equivalent to a two-component system of
      interacting A and B molecules on the sites of a kagome lattice.

PMID- 16605344
TI  - Interfacial properties of liquid-vapor interfaces with planar, spherical, and
      cylindrical geometries in mean field.
AB  - Following the route of the stress tensor we study the free energy of a fluid
      liquid-vapor interface in the van der Waals approximation for planar, cylindrical
      and spherical interfaces. By performing a systematic expansion in powers of the
      inverse of the curvature radii, and appropriately defining the Gibbs dividing
      surface, we find unambiguous expressions for the surface tension, the spontaneous
      curvature, the bending rigidity and the Gaussian rigidity.

PMID- 16605345
TI  - Residual stability of sessile droplets with negative line tension.
AB  - We study the local stability of a sessile droplet with nonvanishing line tension
      along the contact line, where three phases are in equilibrium. We confirm Widom's
      results [J. Phys. Chem. 99, 2803 (1995)] on the local stability of a droplet with
      positive line tension in a larger class of perturbations. When the line tension
      is negative, we prove that the restricted class of perturbations employed by
      Widom fails to capture the instability of equilibria. A notion of residual
      stability is introduced, which makes quantitative the condition under which
      equilibrium of droplets with negative line tension are likely to be observed.

PMID- 16605346
TI  - Theoretical analysis of the vapor-liquid-solid mechanism of nanowire growth
      during molecular beam epitaxy.
AB  - A theoretical model of nanowire formation by the vapor-liquid-solid mechanism
      during molecular beam epitaxy and related growth techniques is presented. The
      model unifies the conventional adsorption-induced model, the diffusion-induced
      model, and the model of nucleation-mediated growth on the liquid-solid interface.
      The concentration of deposit atoms in the liquid alloy, the nanowire diameter,
      and all other characteristics of the growth process are treated dynamically as
      functions of the growth time. The model provides theoretical length-diameter
      dependences of nanowires and the dependence of the nanowire length on the
      technologically controlled growth conditions, such as the surface temperature and
      the deposition thickness. In particular, it is shown that the length-diameter
      curves of nanowires might convert from decreasing to increasing at a certain
      critical diameter and that the nanowires taper when their length becomes
      comparable with the adatom diffusion length on the sidewalls. The theoretical
      dependence of the nanowire morphology on its lateral size and length and on the
      surface temperature are compared to the available experimental data obtained
      recently for Si and nanowires.

PMID- 16605347
TI  - Model of a liquid nanofilm on a solid substrate based on the van der Waals
      concept of capillarity.
AB  - Van der Waals attractive forces drastically change the material properties of
      thin liquid layers several nanometers when in contact with a solid. At this
      scale, the fluid is no longer homogeneous. Moreover, it has properties which are
      analogous to those of solids. In particular, in equilibrium the stress tensor is
      no longer spherical. For such fluids, we use a long-wave approximation to derive
      the evolution of a liquid nanofilm on a substrate. We establish that the driving
      pressure in the nanofilm should be associated with the mean value of the
      component of the pressure tensor tangential to the liquid interface (along the
      substrate). Finally, we derive the equation for nanofilm dynamics by using a mass
      conservation formulation. This is not a conventional, conservative equation for
      the position of the free surface normally used in the theory of thick films where
      the density is homogeneous, but rather a conservative equation for the liquid
      mass. The equation turns out to be a nonlinear parabolic equation with a
      diffusion coefficient of a "good" sign.

PMID- 16605348
TI  - Scaling in the crossover from random to correlated growth.
AB  - In systems where deposition rates are high compared to diffusion, desorption, and
      other mechanisms that generate correlations, a crossover from random to
      correlated growth of surface roughness is expected at a characteristic time t0.
      This crossover is analyzed in lattice models via scaling arguments, with support
      from simulation results presented here and in other works. We argue that the
      amplitudes of the saturation roughness and of the saturation time t(x) scale as
      t0(1/2) and t0, respectively. For models with lateral aggregation, which
      typically are in the Kardar-Parisi-Zhang (KPZ) class, we show that t0
      approximately p(-1), where p is the probability of the correlated aggregation
      mechanism to take place. However, t0 approximately p(-2) is obtained in solid-on
      solid models with single-particle deposition attempts. This group includes models
      in various universality classes, with numerical examples being provided in the
      Edwards-Wilkinson (EW), KPZ, and Villain-Lai-Das Sarma (nonlinear molecular-beam
      epitaxy) classes. Most applications are for two-component models in which random
      deposition, with probability 1-p, competes with a correlated aggregation process
      with probability p. However, our approach can be extended to other systems with
      the same crossover, such as the generalized restricted solid-on-solid model with
      maximum height difference S, for large S. Moreover, the scaling approach applies
      to all dimensions. In the particular case of one-dimensional KPZ processes with
      this crossover, we show that t0 approximately nu(-1) and nu approximately
      lambda(2/3), where nu and lambda are the coefficients of the linear and nonlinear
      terms of the associated KPZ equations. The applicability of previous results to
      models in the EW and KPZ classes is discussed.

PMID- 16605349
TI  - Excess nonspecific Coulomb ion adsorption at the metal electrode/electrolyte
      solution interface: role of the surface layer.
AB  - Excess ion adsorption gamma induced by the polarization image forces in the
      system of a metal electrode/symmetric electrolyte solution separated by an
      insulating interlayer has been calculated. The adopted theoretical scheme
      involves the Coulomb Green's function in a three-layer system with sharp
      interfaces and specular reflection at them. The influence of the spatial
      dispersion of the dielectric permittivities epsilon(i)(k) in all the three media
      on the image force energy W(im) and the adsorption gamma has been analyzed, where
      k is the wave vector. A comparison with the classical model, where
      epsilon(i)=const, has been carried out. It has been shown that both the Debye
      Huckel ion screening and the spatial dispersion of the solvent contribution
      epsilon(solv)(k) to the overall dielectric function epsilon(el)(k) of the
      electrolyte solution lead to the qualitative difference with the results for the
      classical model. In particular, in a wide range of ion concentrations n0 a thin
      interlayer L > or = 5-10 angstroms effectively screens out the attractive
      influence of the metallic electrode, so that the net Coulomb adsorption may
      become repulsive. The approach and the results obtained qualitatively describe
      two physically different situations. Specifically, the introduced interlayer
      corresponds either to the dense near-electrode (inner) electrolyte layer or to
      the intentionally deposited control coating of arbitrary thickness.

PMID- 16605350
TI  - Structure of nematic liquid crystalline elastomers under uniaxial deformation.
AB  - We have used in situ x-ray diffraction and calorimetry to study liquid
      crystalline elastomers prepared using a one-step photopolymerization method. We
      used suspended weights to stretch free-standing crystalline elastomer films. With
      the mechanical stress parallel to the initial director, we observed a gradual
      nematic to isotropic transition with increasing temperature. The thermal
      evolution of the nematic order parameter on cooling, together with the
      observation of isotropic-nematic coexistence over a broad temperature range,
      suggests that the heterogeneity in the samples introduces a distribution of
      transition temperatures. With the mechanical stress perpendicular to the initial
      director, we observed both uniform director rotation and stripe formation,
      depending on the details of sample preparation.

PMID- 16605351
TI  - Photoinduced circular anisotropy in a photochromic W-shaped-molecule-doped
      polymeric liquid crystal film.
AB  - Photoinduced circular anisotropy has been demonstrated in thin films of a main
      chain polymeric liquid crystal (PLC) system doped with photochromic W-shaped
      molecules containing two azobenzene groups by irradiating with circularly
      polarized light (CPL). Reversible photoinduced circular dichroism (CD) was
      observed with sign relevant to the handedness of the CPL. The experimentally
      observed CD spectra were analyzed using the DeVoe polarizability model associated
      with the coupled oscillator method. We also propose a mechanism for the
      photoinduced circular anisotropy in our system; nucleating the W-shaped molecules
      with preferential twisted conformation by CPL irradiation, and triggering the
      local formation of a chiral structure in the W-shaped-molecule-doped main-chain
      PLC medium.

PMID- 16605352
TI  - Simulation of phase separation of polymer-liquid-crystal mixtures and the effect
      of confining external surfaces.
AB  - A Monte Carlo simulation is performed on a lattice model of a binary mixture of
      nematogenic liquids and polymers to study the main aspects of phase separation
      including the influence of external surfaces. The system was investigated at
      various temperatures, concentrations, and degrees of polymerization. The results
      seem to fit well within Flory-Huggins theory predictions. It is also shown that
      in some cases the anisotropy plays an important role in structure formation. The
      influence of the external surfaces on the condensation of one of the phases was
      studied on systems that experience the separation by nucleation and growth. It
      has been noticed that the surfaces that prefer nematogenic molecules act as
      better condensation nuclei, especially if they are ordered.

PMID- 16605353
TI  - Light-induced chaotic rotations in nematic liquid crystals.
AB  - Various nonlinear rotation regimes are observed in an optically excited nematic
      liquid-crystal film under boundary conditions (for the light and material) that
      are invariant by rotation. The excitation light is circularly polarized, the
      intensity profile is circularly symmetric, and the beam diameter at the sample
      location is a few times smaller than the cell thickness. A transition to chaos
      via quasiperiodicity is identified when the light intensity is taken as the
      control parameter. Transverse nonlocal effects are suggested to be the cause of
      the observed dynamics, and a simple model consisting of a collection of coupled
      rotators is developed to provide a qualitative explanation.

PMID- 16605354
TI  - Laser trapping of low refractive index colloids in a nematic liquid crystal.
AB  - We describe and analyze laser trapping of small colloidal particles in a nematic
      liquid crystal, where the index of refraction of colloids is smaller compared to
      the indices of the liquid crystal. Two mechanisms are identified that are
      responsible for this anomalous trapping: (i) below the optical Freedericksz
      transition, the trapping is due to the anisotropic dielectric interaction of the
      polarized light with the inhomogeneous director field around the colloid, (ii)
      above the optical Freedericksz transition, the optical trapping is accompanied by
      the elasticity-mediated interaction between the optically distorted region of a
      liquid crystal and the colloid. In the majority of the experiments, the trapping
      above the Freedericksz transition is highly anisotropic. Qualitative agreement is
      found with a numerical analysis, considering the nematic director elastic
      distortion, dielectric director-light field coupling and optical repulsion due to
      low refraction index colloid in high index surroundings.

PMID- 16605355
TI  - Spatial distribution of polyelectrolyte and counterions in nanocapsules: a
      computer simulation study.
AB  - We study a spatial distribution of polyelectrolyte chains and counterions inside
      nanometer-size capsules by means of molecular dynamics simulation on the level of
      a colloidal model in which polyelectrolyte coils are modeled as soft charged
      spheres. The capsule shell is treated as a semipermeable membrane, impermeable
      for the polyelectrolyte chains, but allowing free diffusion of solvent molecules
      and counterions. As a result, counterions leak out from the capsule immersed into
      a fluid of low ionic strength. This counterion leakage leads to a formation of
      characteristic polyelectrolyte density profiles with the central plateau and
      large peaks at the wall. We show that a nonuniform distribution of the inner
      polyelectrolyte depends on the capsule radius, surface charge, concentration of
      encapsulated polyelectrolyte, and the volume fraction of capsules.

PMID- 16605356
TI  - Theoretical analysis of destabilization resonances in time-delayed stochastic
      second-order dynamical systems and some implications for human motor control.
AB  - A linear stochastic delay differential equation of second order is studied that
      can be regarded as a Kramers model with time delay. An analytical expression for
      the stationary probability density is derived in terms of a Gaussian
      distribution. In particular, the variance as a function of the time delay is
      computed analytically for several parameter regimes. Strikingly, in the parameter
      regime close to the parameter regime in which the deterministic system exhibits
      Hopf bifurcations, we find that the variance as a function of the time delay
      exhibits a sequence of pronounced peaks. These peaks are interpreted as delay
      induced destabilization resonances arising from oscillatory ghost instabilities.
      On the basis of the obtained theoretical findings, reinterpretations of previous
      human motor control studies and predictions for future human motor control
      studies are provided.

PMID- 16605357
TI  - Voltage dependence of the carrier-mediated ion transport.
AB  - With regards to the common features of carrier-mediated transport, voltage
      dependence was studied, using an asymmetric, six-state model. Our study shows
      that for an ion exchanger, transporting one kind of ion via exchange with another
      kind, the ion flux as a function of the membrane potential shows a sigmoidal
      curve with a shallow slope, saturation behavior, and possibly a negative slope.
      These features are mainly due to the transport of ions with charges of the same
      sign in the opposite direction. Membrane potential depolarization can facilitate
      only one transport and hinder another. As a result, the ion flux cannot increase
      dramatically and has an upper limitation because the exchanging rate depends on
      competition of the two inversely voltage-dependent transport processes. In
      contrast, for unidirectional ion transporters, the ion flux will monotonically
      increase as a function of the membrane potential. Both the maximum ion flux and
      the voltage sensitivity are much higher than those of the ion exchanger.

PMID- 16605358
TI  - Meshless membrane model based on the moving least-squares method.
AB  - A meshless particle-based membrane model is proposed. The particles possess no
      internal degree of freedom and interact via a potential, which has three
      different contributions: a short-range repulsive pair potential, an attractive
      multibody potential, and a curvature potential based on the moving least-squares
      method. Brownian dynamics simulations are employed to demonstrate that the
      particles self-assemble into a membrane and to study equilibrium properties, such
      as bending rigidity, surface tension, line tension, and diffusion constant. The
      bending rigidity and line tension are shown to depend on different potential
      parameters and can therefore be varied independently. The finite-size effects of
      nearly planar membranes are investigated. This model is well suited to study the
      membrane dynamics with topological changes.

PMID- 16605359
TI  - Min-protein oscillations in Escherichia coli with spontaneous formation of two
      stranded filaments in a three-dimensional stochastic reaction-diffusion model.
AB  - We introduce a three-dimensional stochastic reaction-diffusion model to describe
      MinD/MinE dynamical structures in Escherichia coli. This model spontaneously
      generates pole-to-pole oscillations of the membrane-associated MinD proteins,
      MinE ring, as well as filaments of the membrane-associated MinD proteins.
      Experimental data suggest MinD filaments are two-stranded. In order to model them
      we assume that each membrane-associated MinD protein can form up to three bonds
      with adjacent membrane-associated MinD molecules and that MinE induced hydrolysis
      strongly depends on the number of bonds MinD has established.

PMID- 16605360
TI  - Single-molecule unzippering experiments on DNA and Peyrard-Bishop-Dauxois model.
AB  - In this paper, we rely on a nonlinear Peyrard-Bishop-Dauxois (PBD) model. This
      mechanical model explains DNA dynamics assuming only transversal oscillations of
      nucleotides. The potential energy for the hydrogen bonds, connecting AT or CG
      base pairs, is modeled by a Morse potential. This potential is characterized by
      the depth D and the inverse width a of the Morse potential well. We discuss one
      type of single molecule manipulation experiments, which we call unzippering
      experiments. It is explained that the highest values of two essential parameters
      of the PBD model, the parameters D and a, can be determined according to the
      results of those experiments. This statement is supported by theoretical
      calculations. We show that the inverse width of the Morse potential well a has
      been overestimated so far. The smallest value for this parameter is determined
      according to the PBD model, which means that a rather narrow interval can be
      assumed. Also, we give an idea how to determine the optimal value of the
      parameter a.

PMID- 16605361
TI  - Effects of distributed transmission speeds on propagating activity in neural
      populations.
AB  - Motivated by experimental evidence, a distribution of axonal transmission speeds
      is introduced into a standard field model of neural populations. The resulting
      field dynamics is analytically studied by a systematic investigation of the
      stability and bifurcations of equilibrium solutions. Using a perturbation
      approach, the effect of distributed speeds on bifurcations of equilibria are
      determined for general connectivity and speed distributions. In addition, a
      nonlinear analysis of traveling fronts is given. It is shown that the variance of
      the speed distribution affects the frequency of bifurcating periodic solutions
      and the phase speed of traveling waves. Moreover, a new effect is discovered
      where the introduction of axonal speed distributions leads to the maximization of
      the traveling front speed.

PMID- 16605362
TI  - Fronts with continuous waiting-time distributions: theory and application to
      virus infections.
AB  - We generalize to arbitrary waiting-time distributions some results which were
      previously derived for discrete distributions. We show that for any two waiting
      time distributions with the same mean delay time, that with higher dispersion
      will lead to a faster front. Experimental data on the speed of virus infections
      in a plaque are correctly explained by the theoretical predictions using a
      Gaussian delay-time distribution, which is more realistic for this system than
      the Dirac delta distribution considered previously [J. Fort and V. Mendez, Phys.
      Rev. Lett. 89, 178101 (2002)].

PMID- 16605363
TI  - Standing waves in the FitzHugh-Nagumo model of cardiac electrical activity.
AB  - When excitable media are submitted to appropriate time dependent boundary
      conditions, a standing wavelike pattern can be observed in the system, as shown
      in recent experiments. In the present analysis, the physical mechanism explaining
      the occurrence of such space-time patterns is shown to be a competition between
      Ohmic diffusion and an action potential propagation across the system, coupled
      with the existence of refractory states for excitable media.

PMID- 16605364
TI  - Energetics of rotational gating mechanisms of an ion channel induced by membrane
      deformation.
AB  - We consider the gating mechanisms of an ion channel which has a conical structure
      for a closed state and a cylindrical or a bottleneck structure for an open state
      depending on the gating mechanisms. Applying the simplified continuum model of
      the membrane in the presence of a strong hydrophobic interaction between the
      channel proteins and the nearby lipid molecules of the membrane, we obtain energy
      differences between closed and open states for two known and one newly proposed
      rotational gating mechanism. We compare the energetics of three gating mechanisms
      and find out the most favorable mechanism under the given biological conditions
      such as hydrophobic mismatch, spontaneous curvature of a monolayer, and membrane
      moduli in our approach. Our results show that spontaneous curvature plays more
      important role in these gating mechanisms than surface tension does. Introducing
      spontaneous curvature to the inner or outer layer of the membrane affects the
      gating mechanism. We also discuss an effect of membrane thickness change due to
      the channel's conformational transition during gating.

PMID- 16605365
TI  - Lag synchrony measures dynamical processes underlying progression of seizure
      states.
AB  - We investigate the dynamics of bursting behavior in an intact hippocampal
      preparation using causal entropy, an adaptive measure of lag synchrony. This
      analysis, together with a heuristic model of coupled bursting networks, separates
      experimentally observed bursting dynamics into two dynamical regimes, when
      bursting is driven by (1) the intranetwork dynamics of a single region, or (2)
      internetwork feedback between spatially disjoint neural populations. Our results
      suggest that the abrupt transition between these two states heralds the gradual
      desynchronization of bursting activity. These results illustrate how
      superficially homogeneous behavior across loosely coupled networks may harbor
      hidden, but robust, dynamical processes.

PMID- 16605366
TI  - Orientation of optically trapped nonspherical birefringent particles.
AB  - While the alignment and rotation of microparticles in optical traps have received
      increased attention recently, one of the earliest examples has been almost
      totally neglected--the alignment of particles relative to the beam axis, as
      opposed to about the beam axis. However, since the alignment torques determine
      how particles align in a trap, they are directly relevant to practical
      applications. Lysozyme crystals are an ideal model system to study factors
      determining the orientation of nonspherical birefringent particles in a trap.
      Both their size and their aspect ratio can be controlled by the growth
      parameters, and their regular shape makes computational modeling feasible. We
      show that both external (shape) and internal (birefringence) anisotropy
      contribute to the alignment torque. Three-dimensionally trapped elongated objects
      either align with their long axis parallel or perpendicular to the beam axis
      depending on their size. The shape-dependent torque can exceed the torque due to
      birefringence, and can align negative uniaxial particles with their optic axis
      parallel to the electric field, allowing an application of optical torque about
      the beam axis.

PMID- 16605368
TI  - Self-organized packs selection in predator-prey ecosystems.
AB  - We present a lattice model of a system of predators of five kinds, competing for
      prey. The predators are grouped in packs and characterized by two parameters-the
      energy spent on hunting and energy gained by the kill. The success of hunting
      depends on the actual competition among predators found near a prey. We determine
      via Monte Carlo simulations the numbers of predators of each kind as a function
      of time and the distribution of the size of their packs. We show that the ratio
      of the energy spent by the competing predators determines their fate. The energy
      gain plays only a secondary role. We show also that the system self-organizes
      itself into groups of predators living in well defined packs, which size depends
      on the energy spent. The most preferred size dependence on the energy spent
      follows a very simple power law. We present also a mean-field-type approach to
      the problem and we discuss the differences in the results obtained by the two
      methods, showing in particular, that the simulation approach produces more
      reliable results.

PMID- 16605367
TI  - Hybrid grammar-based approach to nonlinear dynamical system identification from
      biological time series.
AB  - We introduce a grammar-based hybrid approach to reverse engineering nonlinear
      ordinary differential equation models from observed time series. This hybrid
      approach combines a genetic algorithm to search the space of model architectures
      with a Kalman filter to estimate the model parameters. Domain-specific knowledge
      is used in a context-free grammar to restrict the search space for the functional
      form of the target model. We find that the hybrid approach outperforms a pure
      evolutionary algorithm method, and we observe features in the evolution of the
      dynamical models that correspond with the emergence of favorable model
      components. We apply the hybrid method to both artificially generated time series
      and experimentally observed protein levels from subjects who received the
      smallpox vaccine. From the observed data, we infer a cytokine protein interaction
      network for an individual's response to the smallpox vaccine.

PMID- 16605369
TI  - Structural origin of the colored reflections from the black-billed magpie
      feathers.
AB  - The structural origin of the weak iridescence on some of the dark feathers of the
      black-billed magpie, Pica pica (Corvidae), is found in the structure of the
      ribbon-shaped barbules. The cortex of these barbules contains cylindrical holes
      distributed as the nodes of an hexagonal lattice in the hard layer cross section.
      The cortex optical properties are described starting from a photonic-crystal film
      theory. The yellowish-green coloration of the bird's tail can be explained by the
      appearance of a reflection band related to the photonic-crystal lowest-lying gap.
      The bluish reflections from the wings are produced by a more complicated
      mechanism, involving the presence of a cortex second gap."

PMID- 16605370
TI  - Comparative all-atomic study of unfolding pathways for proteins chymotrypsin
      inhibitor 2 and barnase.
AB  - The features of transition states and intermediates are important in the study on
      protein folding. However, transition states and intermediates could not be
      obviously identified from trajectories obtained by dynamic simulations. In this
      work, a different method to identify and characterize the transition states and
      intermediates by combining the root mean square deviation of C(alpha) atoms and
      the similarity factor Q to the native state is proposed. The unfolding processes
      based on all-atomic simulations for proteins chymotrypsin inhibitor 2 and barnase
      are studied, and the related transition states and intermediates are identified
      by observing an unfolding factor U = 1-F. Comparisons between the conformational
      cluster analysis and experimental results are also made. The various analyses on
      the unfolding behaviors indicate that our method can well define the transition
      states and intermediates, and the factor U (or F) can be used as a reaction
      coordinate of the folding and unfolding process. It is also found that three
      state folding proteins might experience more complicated pathways and have more
      rugged energy landscapes than two-state folding proteins.

PMID- 16605372
TI  - Comprehensive study of pattern formation in relaxational systems.
AB  - We present a comprehensive study of pattern formation in single-field
      relaxational systems with field-dependent coefficients. A modulated mean-field
      theory leads to a form amenable to analysis via the geometric architecture
      developed in our earlier work for systems that exhibit phase transitions between
      global steady states [Phys. Rev. E 69, 011102 (2004)]. We demonstrate that the
      phase diagrams for these systems are entirely determined by a few geometric
      properties of the field-dependent relaxational coefficient and the local
      potential. Numerical simulations support the theoretical predictions.

PMID- 16605371
TI  - Ab initio study of alanine polypeptide chain twisting.
AB  - We have investigated the potential energy surfaces for alanine chains consisting
      of three and six amino acids. For these molecules we have calculated potential
      energy surfaces as a function of the Ramachandran angles and , which are widely
      used for the characterization of the polypeptide chains. These particular degrees
      of freedom are essential for the characterization of the proteins folding
      process. Calculations have been carried out within the ab initio theoretical
      framework based on the density functional theory and accounting for all the
      electrons in the system. We have determined stable conformations and calculated
      the energy barriers for transitions between them. Using a thermodynamic approach,
      we have estimated the times of characteristic transitions between these
      conformations. The results of our calculations have been compared with those
      obtained by other theoretical methods and with the available experimental data
      extracted from the Protein Data Base. This comparison demonstrates a reasonable
      correspondence of the most prominent minima on the calculated potential energy
      surfaces to the experimentally measured angles and for alanine chains appearing
      in native proteins. We have also investigated the influence of the secondary
      structure of polypeptide chains on the formation of the potential energy
      landscape. This analysis has been performed for the sheet and the helix
      conformations of chains of six amino acids.

PMID- 16605373
TI  - Chain dynamics and power-law distance fluctuations of single-molecule systems.
AB  - Chain-dynamics-induced distance fluctuations between any two points in a finite
      chain with or without cross links are investigated. This model leads to three
      regimes of temporal behavior for distance autocorrelation: (i) initial flat time
      dependence, (ii) t(-alpha) power law, and (iii) long-time exponential decay. For
      an ideal Rouse chain with frequency-independent friction, alpha = 1/2. The span
      of the characteristic power-law behavior of a long chain could be reduced
      significantly with the presence of cross links.

PMID- 16605374
TI  - Experimental and theoretical study of vibrational resonance in a bistable system
      with asymmetry.
AB  - We present a theoretical and experimental study of the phenomenon of vibrational
      resonance in a bistable vertical cavity surface emitting laser with asymmetrical
      double-well quasipotential. Several relations, found analytically, are compared
      with the experimental and numerical results. Additionally, we investigate the
      effect of additive noise.

PMID- 16605375
TI  - Heterogeneity-related dynamics in isotropic n-pentylcyanobiphenyl.
AB  - The evolution of the dielectric relaxation time tau(T) and its strong electric
      field related counterpart tau(fluct).(T) in the isotropic phase of rodlike liquid
      crystalline n-pentylcyanobiphenyl (5CB) is discussed. For the tau(fluct).(T) a
      strong pretransitional increase on approaching the virtual critical point located
      at deltaT = 1.1 K below isotropic nematic clearing temperature T(IN) is shown.
      The linearized derivative analysis applied to test the evolution of tau(T)
      revealed a sequence of Vogel-Fulcher-Tammann based dynamical domains, for which
      the fragility increases enormously on approaching T(IN). The similar analysis
      focused on testing the "critical" mode-coupling theory behavior showed superior
      features of such description. A strong asymmetric broadening of the dielectric
      loss curves is also discussed.

PMID- 16605376
TI  - Stochastic model in the Kardar-Parisi-Zhang universality class with minimal
      finite size effects.
AB  - We introduce a solid-on-solid lattice model for growth with conditional
      evaporation. A measure of finite size effects is obtained by observing the time
      invariance of distribution of local height fluctuations. The model parameters are
      chosen so that the change in the distribution in time is minimum. On a one
      dimensional substrate the results obtained from the model for the roughness
      exponent from three different methods are same as predicted for the Kardar-Parisi
      Zhang equation. One of the unique features of the model is that as obtained from
      the structure factor S(k,t) for the one-dimensional substrate growth exactly
      matches the predicted value of 0.5 within statistical errors. The model can be
      defined in any dimensions. We have obtained results for this model on two- and
      three-dimensional substrates.

PMID- 16605377
TI  - Superposition of many independent spike trains is generally not a Poisson
      process.
AB  - We study the sum of many independent spike trains and ask whether the resulting
      spike train has Poisson statistics or not. It is shown that for a non-Poissonian
      statistics of the single spike train, the resulting sum of spikes has exponential
      interspike interval (ISI) distributions, vanishing the ISI correlation at a
      finite lag but exhibits exactly the same power spectrum as the original spike
      train does. This paradox is resolved by considering what happens to ISI
      correlations in the limit of an infinite number of superposed trains.
      Implications of our findings for stochastic models in the neurosciences are
      briefly discussed.

PMID- 16605378
TI  - Statistics of cycles in large networks.
AB  - The occurrence of self-avoiding closed paths (cycles) in networks is studied
      under varying rules of wiring. As a main result, we find that the dependence
      between network size and typical cycle length is algebraic, (h) proportional to
      Nalpha, with distinct values of for different wiring rules. The Barabasi-Albert
      model has alpha=1. Different preferential and nonpreferential attachment rules
      and the growing Internet graph yield alpha<1. Computation of the statistics of
      cycles at arbitrary length is made possible by the introduction of an efficient
      sampling algorithm.

PMID- 16605379
TI  - Anomalous kinetics of attractive A + B-->0 reactions.
AB  - We investigate the kinetics of the A + B-->0 reaction with the attractive
      interaction between opposite species in one spatial dimension. The attractive
      interaction leads to isotropic diffusions inside segregated single species
      domains, and accelerates the reactions of opposite species at the domain
      boundaries. At equal initial densities of and , we analytically and numerically
      show that the density of particles (rho), the size of domains (l), the distance
      between the closest neighbor of same species (lAA), and the distance between
      adjacent opposite species (lAB) scale in time as rho approximately t(-1/3), lAA
      approximately t(1/3), and l approximately lAB approximately lAB(2/3),
      respectively. These dynamical exponents define critical behavior distinguished
      from the class of uniformly driven systems of hard-core particles.

PMID- 16605380
TI  - Scale-free networks emerging from weighted random graphs.
AB  - We study Erdos-Renyi random graphs with random weights associated with each link.
      We generate a "supernode network" by merging all nodes connected by links having
      weights below the percolation threshold (percolation clusters) into a single
      node. We show that this network is scale-free, i.e., the degree distribution is
      P(k) approximately k(-lambda) with lambda=2.5. Our results imply that the minimum
      spanning tree in random graphs is composed of percolation clusters, which are
      interconnected by a set of links that create a scale-free tree with lambda=2.5.
      We suggest that optimization causes the percolation threshold to emerge
      spontaneously, thus creating naturally a scale-free supernode network. We discuss
      the possibility that this phenomenon is related to the evolution of several real
      world scale-free networks.

PMID- 16605381
TI  - Analysis of the ordering transition of hard disks through the Mayer cluster
      expansion.
AB  - The available virial coefficients for the two-dimensional hard-disks model are
      transformed into a matrix representation of the thermodynamic potentials, which
      allows for an accurate description of the whole fluid phase, up to the phase
      transition. We find that the fluid phase terminates at the transition point,
      implying a second-order phase transition in accordance with the Kosterlitz
      Thouless-Halperin-Nelson-Young scenario of a transition into a hexatic phase. The
      density and pressure at the transition are calculated from the available first
      ten virial coefficients, and are found to be in excellent agreement with recent
      Monte-Carlo calculations. Finally, we calculate the equation of state in the
      critical region.

PMID- 16605382
TI  - Crossover from the pair contact process with diffusion to directed percolation.
AB  - Crossover behaviors from the pair contact process with diffusion (PCPD) and the
      driven PCPD (DPCPD) to the directed percolation (DP) are studied in one dimension
      by introducing a single particle annihilation and/or branching dynamics. The
      crossover exponents phi are estimated numerically as 1/phi approximately 0.58 +/-
      0.03 for the PCPD and 1/phi approximately 0.49+/-0.02 for the DPCPD.
      Nontriviality of the PCPD crossover exponent strongly supports the non-DP nature
      of the PCPD critical scaling, which is further evidenced by the anomalous
      critical amplitude scaling near the PCPD point. In addition, we find that the
      DPCPD crossover is consistent with the mean field prediction of the tricritical
      DP class as expected.

PMID- 16605383
TI  - Self-organized criticality and absorbing states: lessons from the Ising model.
AB  - We investigate a suggested path to self-organized criticality. Originally, this
      path was devised to "generate criticality" in systems displaying an absorbing
      state phase transition, but nothing in its definition forbids the mechanism to be
      used in any other continuous phase transition. We used the Ising model as well as
      the Manna model to demonstrate how the finite-size scaling exponents depend on
      the tuning of driving and dissipation rates with system size. Our findings limit
      the explanatory power of the mechanism as it is to nonuniversal critical
      behavior, suggesting that the explanation of self-organized criticality in terms
      of absorbing-state phase transitions is incomplete.

PMID- 16605384
TI  - Quantum lubrication: suppression of friction in a first-principles four-stroke
      heat engine.
AB  - A quantum model of a heat engine resembling the Otto cycle is employed to explore
      strategies to suppress frictional losses. These losses are caused by the
      inability of the engine's working medium to follow adiabatically the change in
      the Hamiltonian during the expansion and compression stages. By adding external
      noise to the engine frictional losses can be suppressed.

PMID- 16605385
TI  - Experimental steady pattern formation in reaction-diffusion-advection systems.
AB  - We present here experimental evidence of a mechanism of a steady-chemical pattern
      formation called "flow-and-diffusion structures" (FDS). Experiments were
      performed using the photosensitive chlorine dioxide-iodine-malonic acid reaction,
      where the differential diffusion can be chemically controlled. Using the analogy
      between an advection boundary and a moving boundary, we obtain the formation of
      spatially periodic steady patterns, which matches all the previously theoretical
      predictions for FDS patterns. Numerical simulations are also reported in
      agreement with the experimental results.

PMID- 16605386
TI  - Wave-vector resonance in a nonlinear multiwavespeed chaotic billiard.
AB  - Nonlinear coupling between eigenmodes of a system leads to spectral energy
      redistribution. For multiwavespeed chaotic billiards, the average coupling
      strength can exhibit sharp discontinuities as a function of frequency related to
      wave-vector coincidences between constituent waves of different wavespeeds. The
      phenomenon is investigated numerically for an ensemble of two-dimensional square
      two-wavespeed billiards with rough boundaries and quadratic nonlinearity
      representative of elastodynamic waves. Results of direct numerical simulations
      are compared with theoretical predictions.

PMID- 16605387
TI  - Hexagonal convection patterns in atomistically simulated fluids.
AB  - Molecular dynamics simulation has been used to model pattern formation in three
      dimensional Rayleigh-Benard convection at the discrete-particle level. Two
      examples are considered, one in which an almost perfect array of hexagonally
      shaped convection rolls appears, the other a much narrower system that forms a
      set of linear rolls; both pattern types are familiar from experiment. The nature
      of the flow within the convection cells and quantitative aspects of the
      development of the hexagonal planform based on automated polygon subdivision are
      analyzed. Despite the microscopic scale of the system, relatively large
      simulations with several million particles and integration time steps are
      involved.

PMID- 16605388
TI  - Clustering of randomly advected low-inertia particles: a solvable model.
AB  - Measurements and simulations indicate that the particle-pair radial distribution
      function in isotropic turbulence is a power law in a range of length scales below
      the Kolmogorov scale for Stokes number St<<1. In this range, the exponent is
      proportional to St1St2 for unlike particles (1 and 2) in a bidispersion, hence
      St2 for a monodispersion. Here, this result is derived from a model of particle
      response to random advection. The analysis generalizes a geometrical
      interpretation of clustering to polydispersions and suggests an economical Monte
      Carlo simulation method.

PMID- 16605389
TI  - Nonlinear development of stimulated Raman scattering from electrostatic modes
      excited by self-consistent non-Maxwellian velocity distributions.
AB  - The parametric coupling involving backward stimulated scattering of a laser and
      electron beam acoustic modes (BAM) is described as observed in particle-in-cell
      (PIC) simulations. The BAM modes evolve from Langmuir waves (LW) as the electron
      velocity distribution is nonlinearly modified to be non-Maxwellian by backward
      stimulated Raman scattering (BSRS). With a marginal damping rate, BAM can be
      easily excited and allow an extended chirping in frequency to occur as later SRS
      pulses encounter modified distributions. Coincident with the emergence of this
      non-Maxwellian distribution is a rapid increase in BSRS reflectivities with laser
      intensities. Both the reflectivity scaling with laser intensity and the observed
      spectral features from PIC simulations are consistent with recent Trident
      experiments.

PMID- 16605390
TI  - Three-dimensional spatiotemporal optical solitons in nonlocal nonlinear media.
AB  - We demonstrate the existence of stable three-dimensional spatiotemporal solitons
      (STSs) in media with a nonlocal cubic nonlinearity. Fundamental (nonspinning)
      STSs forming one-parameter families are stable if their propagation constant
      exceeds a certain critical value that is inversely proportional to the range of
      nonlocality of nonlinear response. All spinning three-dimensional STSs are found
      to be unstable.

PMID- 16605391
TI  - Persistence and the random bond Ising model in two dimensions.
AB  - We study the zero-temperature persistence phenomenon in the random bond +/-J
      Ising model on a square lattice via extensive numerical simulations. We find
      strong evidence for "blocking" regardless of the amount disorder present in the
      system. The fraction of spins which never flips displays interesting
      nonmonotonic, double-humped behavior as the concentration of ferromagnetic bonds
      is varied from zero to one. The peak is identified with the onset of the zero
      temperature spin glass transition in the model. The residual persistence is found
      to decay algebraically and the persistence exponent theta(p) approximately = 0.9
      over the range 0.1< or =p< or =0.9. Our results are completely consistent with
      the result of Gandolfi, Newman, and Stein for infinite systems that this model
      has "mixed" behavior, namely positive fractions of spins that flip finitely and
      infinitely often, respectively. [Gandolfi, Newman and Stein, Commun. Math. Phys.
      214, 373 (2000).].

PMID- 16605392
TI  - Numerical method for solving stochastic differential equations with dichotomous
      noise.
AB  - We propose a numerical method for solving stochastic differential equations with
      dichotomous Markov noise. The numerical scheme is formulated such that (i) the
      stochastic formula used follows the Stratonovich-Taylor form over the entire
      range of noise correlation times, including the Gaussian white noise limit; and
      (ii) the method is readily applicable to dynamical systems driven by arbitrary
      types of noise, provided there exists a way to describe the random increment of
      the stochastic process expressed in the Stratonovich-Taylor form. We further
      propose a simplified Taylor scheme that significantly reduces the computation
      time, while still satisfying the moment properties up to the required order. The
      accuracies and efficiencies of the proposed algorithms are validated by applying
      the schemes to two prototypical model systems that possess analytical solutions.

PMID- 16605393
TI  - Nonextensive models for earthquakes.
AB  - We have revisited the fragment-asperity interaction model recently introduced by
      Sotolongo-Costa and Posadas [Phy. Rev. Lett. 92, 048501 (2004)] by considering a
      different definition for mean values in the context of Tsallis nonextensive
      statistics and introducing a scale between the earthquake energy and the size of
      fragment epsilon proportional to r3. The energy-distribution function (EDF)
      deduced in our approach is considerably different from the one obtained in the
      above reference. We have also tested the viability of this EDF with data from two
      different catalogs (in three different areas), namely, the NEIC and the Bulletin
      Seismic of the Revista Brasileira de Geofisica. Although both approaches provide
      very similar values for the nonextensive parameter , other physical quantities,
      e.g., energy density, differ considerably by several orders of magnitude.

PMID- 16605394
TI  - Ring structures and mean first passage time in networks.
AB  - In this paper we address the problem of the calculation of the mean first passage
      time on generic graphs. We focus in particular on the mean first passage time on
      a node for a random walker starting from a generic, unknown, node x. We introduce
      an approximate scheme of calculation which maps the original process in a Markov
      process in the space of the so-called rings, described by a transition matrix of
      size O(ln N/ln (k) x ln N/ln (k)), where is the size of the graph and (k) the
      average degree in the graph. In this way one has a drastic reduction of degrees
      of freedom with respect to the size of the transition matrix of the original
      process, corresponding to an extremely low computational cost. We first apply the
      method to the Erdos-Renyi random graphs for which the method allows for almost
      perfect agreement with numerical simulations. Then we extend the approach to the
      Barabasi-Albert graph, as an example of scale-free graph, for which one obtains
      excellent results. Finally we test the method with two real-world graphs,
      Internet and a network of the brain, for which we obtain accurate results.

PMID- 16605395
TI  - Critical line of an n-component cubic model.
AB  - We consider a special case of the -component cubic model on the square lattice,
      for which an expansion exists in Ising-type graphs. We construct a transfer
      matrix and perform a finite-size-scaling analysis to determine the critical
      points for several values of . Furthermore we determine several universal
      quantities, including three critical exponents. For , these results agree well
      with the theoretical predictions for the critical branch. This model is also a
      special case of the model of Domany and Riedel. It appears that the self-dual
      plane of the latter model contains the exactly known critical points of the and 2
      cubic models. For this reason we have checked whether this is also the case for .
      However, this possibility is excluded by our numerical results.

PMID- 16605396
TI  - Generalized canonical ensembles and ensemble equivalence.
AB  - This paper is a companion piece to our previous work [J. Stat. Phys. 119, 1283
      (2005)], which introduced a generalized canonical ensemble obtained by
      multiplying the usual Boltzmann weight factor of the canonical ensemble with an
      exponential factor involving a continuous function of the Hamiltonian . We
      provide here a simplified introduction to our previous work, focusing now on a
      number of physical rather than mathematical aspects of the generalized canonical
      ensemble. The main result discussed is that, for suitable choices of , the
      generalized canonical ensemble reproduces, in the thermodynamic limit, all the
      microcanonical equilibrium properties of the many-body system represented by even
      if this system has a nonconcave microcanonical entropy function. This is
      something that in general the standard canonical ensemble cannot achieve. Thus a
      virtue of the generalized canonical ensemble is that it can often be made
      equivalent to the microcanonical ensemble in cases in which the canonical
      ensemble cannot. The case of quadratic functions is discussed in detail; it leads
      to the so-called Gaussian ensemble.

PMID- 16605397
TI  - Motion of a random walker in a quenched power law correlated velocity field.
AB  - We study the motion of a random walker in one longitudinal and transverse
      dimensions with a quenched power law correlated velocity field in the
      longitudinal direction. The model is a modification of the Matheron-de Marsily
      model, with long-range velocity correlation. For a velocity correlation function,
      dependent on transverse coordinates as , we analytically calculate the two-time
      correlation function of the coordinate. We find that the motion of the coordinate
      is a fractional Brownian motion (FBM), with a Hurst exponent . From this and
      known properties of FBM, we calculate the disorder averaged persistence
      probability of up to time . We also find the lines in the parameter space of and
      along which there is marginal behavior. We present results of simulations which
      support our analytical calculation.

PMID- 16605398
TI  - Bump formation in a binary attractor neural network.
AB  - The conditions for the formation of local bumps in the activity of binary
      attractor neural networks with spatially dependent connectivity are investigated.
      We show that these formations are observed when asymmetry between the activity
      during the retrieval and learning is imposed. An analytical approximation for the
      order parameters is derived. The corresponding phase diagram shows a relatively
      large and stable region where this effect is observed, although critical storage
      and information capacities drastically decrease inside that region. We
      demonstrate that the stability of the network, when starting from the bump
      formation, is larger than the stability when starting even from the whole
      pattern. Finally, we show a very good agreement between the analytical results
      and the simulations performed for different topologies of the network.

PMID- 16605399
TI  - Probabilistic dynamics of some jump-diffusion systems.
AB  - Some exact solutions to the forward Chapman-Kolmogorov equation are derived for
      processes driven by both Gaussian and compound Poisson (shot) noise. The combined
      action of these two forms of white noise is analyzed in transient and equilibrium
      conditions for different jump distributions and additive Gaussian noise. Steady
      state distributions with power-law tails are obtained for exponentially
      distributed jumps and multiplicative linear Gaussian noise. Two applications are
      discussed: namely, the virtual waiting-time or Takacs process including Gaussian
      oscillations and a simplified model of soil moisture dynamics, in which rainfall
      is modeled as a compound Poisson process and fluctuations in potential
      evapotranspiration are Gaussian.

PMID- 16605400
TI  - Molecular heat pump.
AB  - We propose a molecular device that pumps heat against a thermal gradient. The
      system consists of a molecular element connecting two thermal reservoirs that are
      characterized by different spectral properties. The pumping action is achieved by
      applying an external force that periodically modulates molecular levels. This
      modulation affects periodic oscillations of the internal temperature of the
      molecule and the strength of its coupling to each reservoir resulting in a net
      heat flow in the desired direction. The heat flow is examined in the slow and
      fast modulation limits and for different modulation wave forms, thus making it
      possible to optimize the device performance.

PMID- 16605401
TI  - Onsager-Casimir reciprocal relations based on the Boltzmann equation and gas
      surface interaction: single gas.
AB  - The approach to the nonequilibrium thermodynamics based on the Boltzmann equation
      and gas-surface interaction law proposed in previous papers [F. Sharipov, Physica
      A 203, 457 (1994); 209, 457 (1994)] is generalized considering kinetic
      coefficients, which are neither odd nor even with respect to time reversal. It is
      proved that the reciprocity of the gas-gas and gas-surface interactions is a
      necessary and sufficient condition to derive the symmetry of the Onsager matrix.
      As an example of the generalized theory, the thermal slip coefficients are
      related to the heat flux vector appearing in the isothermal shear gas flow in a
      semi-infinite space, i.e., both viscous and thermal slip coefficients can be
      calculated simultaneously, solving a unique kinetic coefficient.

PMID- 16605402
TI  - Traffic dynamics based on local routing protocol on a scale-free network.
AB  - We propose a packet routing strategy with a tunable parameter based on the local
      structural information of a scale-free network. As free traffic flow on the
      communication networks is key to their normal and efficient functioning, we focus
      on the network capacity that can be measured by the critical point of phase
      transition from free flow to congestion. Simulations show that the maximal
      capacity corresponds to alpha= -1 in the case of identical nodes' delivering
      ability. To explain this, we investigate the number of packets of each node
      depending on its degree in the free flow state and observe the power law
      behavior. Other dynamic properties including average packets traveling time and
      traffic load are also studied. Inspiringly, our results indicate that some
      fundamental relationships exist between the dynamics of synchronization and
      traffic on the scale-free networks.

PMID- 16605403
TI  - Periodical survival or decay of traveling impulse in a model of a one-dimensional
      reaction-diffusion system.
AB  - A two-variable model of a one-dimensional (1D), open, excitable reaction
      diffusion system describing space-time evolutions of traveling impulses is
      investigated. It is shown that depending on the size of the system, the traveling
      impulse can survive or decay. Continuous increase of the size of the system
      causes periodical repetitions of surviving and decay of the impulse. The
      qualitative properties of the model, which allow us to expect the phenomenon, are
      described. Numerical solutions confirm this expectation. The chemical reaction
      scheme is realistic and may be a stimulus for seeking the phenomenon in
      experiments.

PMID- 16605404
TI  - Nonlinear model dynamics for closed-system, constrained, maximal-entropy
      generation relaxation by energy redistribution.
AB  - We discuss a nonlinear model for relaxation by energy redistribution within an
      isolated, closed system composed of noninteracting identical particles with
      energy levels with . The time-dependent occupation probabilities are assumed to
      obey the nonlinear rate equations where and are functionals of the 's that
      maintain invariant the mean energy and the normalization condition . The entropy
      is a nondecreasing function of time until the initially nonzero occupation
      probabilities reach a Boltzmann-like canonical distribution over the occupied
      energy eigenstates. Initially zero occupation probabilities, instead, remain zero
      at all times. The solutions of the rate equations are unique and well defined for
      arbitrary initial conditions and for all times. The existence and uniqueness both
      forward and backward in time allows the reconstruction of the ancestral or
      primordial lowest entropy state. By casting the rate equations in terms not of
      the 's but of their positive square roots , they unfold from the assumption that
      time evolution is at all times along the local direction of steepest entropy
      ascent or, equivalently, of maximal entropy generation. These rate equations have
      the same mathematical structure and basic features as the nonlinear dynamical
      equation proposed in a series of papers ending with G. P. Beretta, Found. Phys.
      17, 365 (1987) and recently rediscovered by S. Gheorghiu-Svirschevski [Phys. Rev.
      A 63, 022105 (2001);63, 054102 (2001)]. Numerical results illustrate the features
      of the dynamics and the differences from the rate equations recently considered
      for the same problem by M. Lemanska and Z. Jaeger [Physica D 170, 72 (2002)]. We
      also interpret the functionals and as nonequilibrium generalizations of the
      thermodynamic-equilibrium Massieu characteristic function and inverse
      temperature, respectively.

PMID- 16605405
TI  - Physical realizability of small-world networks.
AB  - Supplementing a lattice with long-range connections effectively models small
      world networks characterized by a high local and global interconnectedness
      observed in systems ranging from society to the brain. If the links have a wiring
      cost associated with their length l, the corresponding distribution q(l) plays a
      crucial role. Uniform length distributions have received the most attention
      despite indications that q(l) approximately l(-alpha) exists-e.g., for integrated
      circuits, the Internet, and cortical networks. While length distributions of this
      type were previously examined in the context of navigability, we here discuss for
      such systems the emergence and physical realizability of small-world topology.
      Our simple argument allows us to understand under which condition and at what
      expense a small world results.

PMID- 16605406
TI  - Power-law distributions from additive preferential redistributions.
AB  - We introduce a nongrowth model that generates the power-law distribution with the
      Zipf exponent. There are elements, each of which is characterized by a quantity,
      and at each time step these quantities are redistributed through binary random
      interactions with a simple additive preferential rule, while the sum of
      quantities is conserved. The situation described by this model is similar to
      those of closed -particle systems when conservative two-body collisions are only
      allowed. We obtain stationary distributions of these quantities both analytically
      and numerically while varying parameters of the model, and find that the model
      exhibits the scaling behavior for some parameter ranges. Unlike well-known growth
      models, this alternative mechanism generates the power-law distribution when the
      growth is not expected and the dynamics of the system is based on interactions
      between elements. This model can be applied to some examples such as personal
      wealths, city sizes, and the generation of scale-free networks when only rewiring
      is allowed.

PMID- 16605407
TI  - Topological nonconnectivity threshold in long-range spin systems.
AB  - We demonstrate the existence of a topological disconnection threshold, recently
      found by Borgonovi [J. Stat. Phys. 116, 1435 (2004)], for generic 1-d anisotropic
      Heisenberg models interacting with an interparticle potential R(-alpha) when
      0<alpha<1(here R is the distance among spins). We also show that alpha if is
      greater than the embedding dimension then the ratio between the disconnected
      energy region and the total energy region goes to zero when the number of spins
      becomes very large. On the other hand, numerical simulations in d=2,3 for the
      long-range case support the conclusion that such a ratio remains finite for large
      N values. The disconnection threshold can thus be thought of as a distinctive
      property of anisotropic long-range interacting systems.

PMID- 16605408
TI  - Scaling and memory of intraday volatility return intervals in stock markets.
AB  - We study the return interval tau between price volatilities that are above a
      certain threshold q for 31 intraday data sets, including the Standard and Poor's
      500 index and the 30 stocks that form the Dow Jones Industrial index. For
      different threshold q, the probability density function Pq(tau)scales with the
      mean interval tau as [Formula: see text], similar to that found in daily
      volatilities. Since the intraday records have significantly more data points
      compared to the daily records, we could probe for much higher thresholds and
      still obtain good statistics. We find that the scaling function f(x)is consistent
      for all 31 intraday data sets in various time resolutions, and the function is
      well-approximated by the stretched exponential, f(x) similar to e(-ax)(gamma),
      with gamma=0.38+/-0.05 and a=3.9+/-0.5, which indicates the existence of
      correlations. We analyze the conditional probability distribution Pq(tau/tau0)
      for tau following a certain interval tau0, and find Pq(tau/tau0) depends on tau0,
      which demonstrates memory in intraday return intervals. Also, we find that the
      mean conditional interval (tau/tau0) increases with tau0, consistent with the
      memory found for Pq(tau/tau0). Moreover, we find that return interval records, in
      addition to having short-term correlations as demonstrated by Pq(tau/tau0), have
      long-term correlations with correlation exponents similar to that of volatility
      records.

PMID- 16605409
TI  - Properties of attractors of canalyzing random Boolean networks.
AB  - We study critical random Boolean networks with two inputs per node that contain
      only canalyzing functions. We present a phenomenological theory that explains how
      a frozen core of nodes that are frozen on all attractors arises. This theory
      leads to an intuitive understanding of the system's dynamics as it demonstrates
      the analogy between standard random Boolean networks and networks with canalyzing
      functions only. It reproduces correctly the scaling of the number of nonfrozen
      nodes with system size. We then investigate numerically attractor lengths and
      numbers, and explain the findings in terms of the properties of relevant
      components. In particular we show that canalyzing networks can contain very long
      attractors, albeit they occur less often than in standard networks.

PMID- 16605410
TI  - Averaged time evolution of rough surfaces.
AB  - We propose a method of extracting an approximated evolution equation of
      distribution of height fluctuations for a class of discrete growth models of
      rough surfaces where the behavior of local slopes can be described by a Markov
      process. Using the Markov property of the fluctuating field, the evolution
      equation is obtained as a map describing the time evolution averaged over
      possible growth paths. Applying the method to a -dimensional restricted solid-on
      solid model, we obtain a map with finite degrees of freedom. The obtained map
      describes well the averaged evolution of surfaces.

PMID- 16605411
TI  - Vertex similarity in networks.
AB  - We consider methods for quantifying the similarity of vertices in networks. We
      propose a measure of similarity based on the concept that two vertices are
      similar if their immediate neighbors in the network are themselves similar. This
      leads to a self-consistent matrix formulation of similarity that can be evaluated
      iteratively using only a knowledge of the adjacency matrix of the network. We
      test our similarity measure on computer-generated networks for which the expected
      results are known, and on a number of real-world networks.

PMID- 16605412
TI  - Fluctuation theorem for constrained equilibrium systems.
AB  - We discuss the fluctuation properties of equilibrium chaotic systems with
      constraints such as isokinetic and Nose-Hoover thermostats. Although the dynamics
      of these systems does not typically preserve phase-space volumes, the average
      phase-space contraction rate vanishes, so that the stationary states are smooth.
      Nevertheless, finite-time averages of the phase-space contraction rate have
      nontrivial fluctuations which we show satisfy a simple version of the Gallavotti
      Cohen fluctuation theorem, complementary to the usual fluctuation theorem for
      nonequilibrium stationary states and appropriate to constrained equilibrium
      states. Moreover, we show that these fluctuations are distributed according to a
      Gaussian curve for long enough times. Three different systems are considered
      here: namely, (i) a fluid composed of particles interacting with Lennard-Jones
      potentials, (ii) a harmonic oscillator with Nose-Hoover thermostatting, and (iii)
      a simple hyperbolic two-dimensional map.

PMID- 16605413
TI  - Finite-connectivity spin-glass phase diagrams and low-density parity check codes.
AB  - We obtain phase diagrams of regular and irregular finite-connectivity spin
      glasses. Contact is first established between properties of the phase diagram and
      the performance of low-density parity check (LDPC) codes within the replica
      symmetric (RS) ansatz. We then study the location of the dynamical and critical
      transition points of these systems within the one step replica symmetry breaking
      theory (RSB), extending similar calculations that have been performed in the past
      for the Bethe spin-glass problem. We observe that the location of the dynamical
      transition line does change within the RSB theory, in comparison with the results
      obtained in the RS case. For LDPC decoding of messages transmitted over the
      binary erasure channel we find, at zero temperature and rate , an RS critical
      transition point at while the critical RSB transition point is located at , to be
      compared with the corresponding Shannon bound . For the binary symmetric channel
      we show that the low temperature reentrant behavior of the dynamical transition
      line, observed within the RS ansatz, changes its location when the RSB ansatz is
      employed; the dynamical transition point occurs at higher values of the channel
      noise. Possible practical implications to improve the performance of the state-of
      the-art error correcting codes are discussed.

PMID- 16605414
TI  - Finite driving rate and anisotropy effects in landslide modeling.
AB  - In order to characterize landslide frequency-size distributions and individuate
      hazard scenarios and their possible precursors, we investigate a cellular
      automaton where the effects of a finite driving rate and the anisotropy are taken
      into account. The model is able to reproduce observed features of landslide
      events, such as power-law distributions, as experimentally reported. We analyze
      the key role of the driving rate and show that, as it is increased, a crossover
      from power-law to non-power-law behaviors occurs. Finally, a systematic
      investigation of the model on varying its anisotropy factors is performed and the
      full diagram of its dynamical behaviors is presented.

PMID- 16605415
TI  - Basic properties of a three-dimensional spring-block model with long-range stress
      transfer.
AB  - Spring-block models have been very useful for understanding slip complexity of
      earthquakes. So far, however, they have been restricted to one or two dimensions
      or simple nearest-neighbor stress transfer. Here, we set up a three-dimensional
      spring-block model with long-range stress transfer and, in a second step,
      implement several simplifications to realize a considerable gain in computational
      efficiency. Qualitatively, the two versions do not differ and we use the fast
      version to investigate basic properties of the model and to compare to the Olami
      Feder Christensen (OFC) model. The spatial distribution of hypocenters is found
      to be scale free. At the end of a simulation of events 10(7), it takes a value of
      D2 approximately = 1.8+/-0.1. At this point, however, the spatial slip
      organization is not stationary yet and the fractal dimension still grows
      slightly. This does not affect respective frequency size statistics, though,
      which exhibit a clear power law with a characteristic cutoff that depends on the
      grid size. The statistics appear smoother than in the OFC model and lack the kink
      between events of size 1 and 2. In addition, strong periodicities of large events
      as in the OFC model do not occur in our model. In stark contrast to the OFC
      model, results remain the same if periodic boundaries are used. Another
      significant difference is the stableness of results against imposed disorder.
      Contrary to the OFC model, results do not change if threshold values are randomly
      distributed in an interval of +/-10% around the mean value. Concluding, the model
      that we propose shares the main properties of the OFC model, but outreaches the
      latter in being stable in a larger set of configurations.

PMID- 16605416
TI  - Master singular behavior from correlation length measurements for seven one
      component fluids near their gas-liquid critical point.
AB  - We present the master (i.e., unique) behavior of the correlation length, as a
      function of the thermal field along the critical isochore, asymptotically close
      to the gas-liquid critical point of xenon, krypton, argon, helium-3, sulfur
      hexafluoride, carbon dioxide, and heavy water. It is remarkable that this unicity
      extends to the correction-to-scaling terms. The critical parameter set, which
      contains all the needed information to reveal the master behavior, is composed of
      four thermodynamic coordinates of the critical point and one adjustable parameter
      which accounts for quantum effects in the helium-3 case. We use a scale
      dilatation method applied to the relevant physical variables of the one-component
      fluid subclass, in analogy with the basic hypothesis of the renormalization
      theory. This master behavior for the correlation length satisfies hyperscaling.
      We finally estimate the thermal field extent where the critical crossover of the
      singular thermodynamic and correlation functions deviates from the theoretical
      crossover function obtained from field theory.

PMID- 16605417
TI  - Critical and tricritical singularities of the three-dimensional random-bond Potts
      model for large.
AB  - We study the effect of varying strength delta of bond randomness on the phase
      transition of the three-dimensional Potts model for large q. The cooperative
      behavior of the system is determined by large correlated domains in which the
      spins point in the same direction. These domains have a finite extent in the
      disordered phase. In the ordered phase there is a percolating cluster of
      correlated spins. For a sufficiently large disorder delta>deltat this percolating
      cluster coexists with a percolating cluster of noncorrelated spins. Such a
      coexistence is only possible in more than two dimensions. We argue and check
      numerically that deltat is the tricritical disorder, which separates the first-
      and second-order transition regimes. The tricritical exponents are estimated as
      betat/vt=0.10(2) and vt=0.67(4). We claim these exponents are q independent for
      sufficiently large q. In the second-order transition regime the critical
      exponents betat/vt=0.60(2) and vt=0.73(1) are independent of the strength of
      disorder.

PMID- 16605418
TI  - Thermodynamics of entropy-driven phase transformations.
AB  - Thermodynamic properties of one-dimensional lattice models exhibiting entropy
      driven phase transformations are discussed in quantum and classical regimes.
      Motivated by the multistability of compounds exhibiting photoinduced phase
      transitions, we consider systems with asymmetric, double, and triple well on-site
      potential. One finds that among a variety of regimes, quantum versus classical,
      discrete versus continuum, a key feature is asymmetry distinguished as a "shift"
      type and "shape" type in limiting cases. The behavior of the specific heat
      indicates one phase transformation in a "shift" type and a sequence of two phase
      transformations in "shape"-type systems. Future analysis in higher dimensions
      should allow us to identify which of these entropy-driven phase transformations
      would evolve into phase transitions of the first order.

PMID- 16605419
TI  - Dissipative process under a boundary perturbation.
AB  - A dissipative process in systems subjected to a boundary perturbation is analyzed
      on the basis of quantum mechanics. We show that the response of the system to the
      perturbation can be expressed in terms of the first-passage time defined
      appropriately by quantum mechanics. In other words, the first-passage-time
      distribution plays the role of the response function in the linear response
      theory. We apply this formalism to the one-dimensional Anderson model in which a
      current is introduced at one end of the system and the other is connected to an
      absorbing wall. We find that the frequency-dependent oscillations of the
      susceptibility reflect the narrowness of the first-passage-time distribution in
      disordered systems.

PMID- 16605420
TI  - Periodicity and growth in a lattice gas with dynamical geometry.
AB  - We study a one-dimensional lattice gas "dynamical geometry model" in which local
      reversible interactions of counter-rotating groups of particles on a ring can
      create or destroy lattice sites. We exhibit many periodic orbits and show that
      all other solutions have asymptotically growing lattice length in both directions
      of time. We explain why the length grows as squareroot of t in all cases
      examined. We completely solve the dynamics for small numbers of particles with
      arbitrary initial conditions.

PMID- 16605422
TI  - Energy dissipation and violation of the fluctuation-response relation in
      nonequilibrium Langevin systems.
AB  - The fluctuation-response relation is a fundamental relation that is applicable to
      systems near equilibrium. On the other hand, when a system is driven far from
      equilibrium, this relation is violated in general because the detailed-balance
      condition is not satisfied in nonequilibrium systems. Even in this case, it has
      been found that for a class of Langevin equations, there exists an equality
      between the extent of violation of the fluctuation-response relation in the
      nonequilibrium steady state and the rate of energy dissipation from the system
      into the environment [T. Harada and S.-i. Sasa, Phys. Rev. Lett. 95, 130602
      (2005)]. Since this equality involves only experimentally measurable quantities,
      it serves as a proposition to determine experimentally whether the system can be
      described by a Langevin equation. Furthermore, the contribution of each degree of
      freedom to the rate of energy dissipation can be determined based on this
      equality. In this paper, we present a comprehensive description on this equality,
      and provide a detailed derivation for various types of models including many-body
      systems, Brownian motor models, time-dependent systems, and systems with multiple
      heat reservoirs.

PMID- 16605421
TI  - Scale invariance in road networks.
AB  - We study the topological and geographic structure of the national road networks
      of the United States, England, and Denmark. By transforming these networks into
      their dual representation, where roads are vertices and an edge connects two
      vertices if the corresponding roads ever intersect, we show that they exhibit
      both topological and geographic scale invariance. That is, we show that for
      sufficiently large geographic areas, the dual degree distribution follows a power
      law with exponent 2.2< or = alpha < or =2.4, and that journeys, regardless of
      their length, have a largely identical structure. To explain these properties, we
      introduce and analyze a simple fractal model of road placement that reproduces
      the observed structure, and suggests a testable connection between the scaling
      exponent and the fractal dimensions governing the placement of roads and
      intersections.

PMID- 16605423
TI  - Time-dependent properties of a simplified Fermi-Ulam accelerator model.
AB  - The chaotic low-energy region of a simplified Fermi-Ulam accelerator model is
      investigated numerically to determine the average energy and number of collisions
      as functions of time. We find that these properties exhibit scaling when the
      oscillation amplitude of the moving wall is small. Following a transient regime,
      the average energy increases in time, reaches a maximum and then shows a
      surprising slow decay.

PMID- 16605424
TI  - Synchronization universality classes and stability of smooth coupled map
      lattices.
AB  - We study two problems related to spatially extended systems: the dynamical
      stability and the universality classes of the replica synchronization transition.
      We use a simple model of one-dimensional coupled map lattices and show that
      chaotic behavior implies that the synchronization transition belongs to the
      multiplicative noise universality class, while stable chaos implies that the
      synchronization transition belongs to the directed percolation universality
      class.

PMID- 16605425
TI  - Coarse-graining of cellular automata, emergence, and the predictability of
      complex systems.
AB  - We study the predictability of emergent phenomena in complex systems. Using
      nearest-neighbor, one-dimensional cellular automata (CA) as an example, we show
      how to construct local coarse-grained descriptions of CA in all classes of
      Wolfram's classification. The resulting coarse-grained CA that we construct are
      capable of emulating the large-scale behavior of the original systems without
      accounting for small-scale details. Several CA that can be coarse-grained by this
      construction are known to be universal Turing machines; they can emulate any CA
      or other computing devices and are therefore undecidable. We thus show that
      because in practice one only seeks coarse-grained information, complex physical
      systems can be predictable and even decidable at some level of description. The
      renormalization group flows that we construct induce a hierarchy of CA rules.
      This hierarchy agrees well with apparent rule complexity and is therefore a good
      candidate for a complexity measure and a classification method. Finally we argue
      that the large-scale dynamics of CA can be very simple, at least when measured by
      the Kolmogorov complexity of the large-scale update rule, and moreover exhibits a
      novel scaling law. We show that because of this large-scale simplicity, the
      probability of finding a coarse-grained description of CA approaches unity as one
      goes to increasingly coarser scales. We interpret this large-scale simplicity as
      a pattern formation mechanism in which large-scale patterns are forced upon the
      system by the simplicity of the rules that govern the large-scale dynamics.

PMID- 16605426
TI  - 1/f noise and very high spectral rigidity.
AB  - It was recently pointed out that the spectral fluctuations of quantum systems are
      formally analogous to discrete time series, and therefore their structure can be
      characterized by the power spectrum of the signal. Moreover, it is found that the
      power spectrum of chaotic spectra displays a 1/f behavior, while that of regular
      systems follows a 1/f2 law. This analogy provides a link between the concepts of
      spectral rigidity and antipersistence. Trying to get a deeper understanding of
      this relationship, we have studied the correlation structure of spectra with high
      spectral rigidity. Using an appropriate family of random Hamiltonians, we
      increase the spectral rigidity up to hindering completely the spectral
      fluctuations. Analyzing the long range correlation structure a neat power law 1/f
      has been found for all the spectra, along the whole process. Therefore, 1/f noise
      is the characteristic fingerprint of a transition that, preserving the scale-free
      correlation structure, hinders completely the fluctuations of the spectrum.

PMID- 16605427
TI  - Occurrence of normal and anomalous diffusion in polygonal billiard channels.
AB  - From extensive numerical simulations, we find that periodic polygonal billiard
      channels with angles which are irrational multiples of pi generically exhibit
      normal diffusion (linear growth of the mean squared displacement) when they have
      a finite horizon, i.e., when no particle can travel arbitrarily far without
      colliding. For the infinite horizon case we present numerical tests showing that
      the mean squared displacement instead grows asymptotically as t ln t. When the
      unit cell contains accessible parallel scatterers, however, we always find
      anomalous super-diffusion, i.e., power-law growth with an exponent larger than .
      This behavior cannot be accounted for quantitatively by a simple continuous-time
      random walk model. Instead, we argue that anomalous diffusion correlates with the
      existence of families of propagating periodic orbits. Finally we show that when a
      configuration with parallel scatterers is approached there is a crossover from
      normal to anomalous diffusion, with the diffusion coefficient exhibiting a power
      law divergence.

PMID- 16605428
TI  - General quantum resonances of the kicked particle.
AB  - The quantum resonances (QRs) of the kicked particle are studied in a most general
      framework by also considering arbitrary periodic kicking potentials. It is shown
      that QR can arise, in general, for any rational value of the Bloch quasimomentum.
      This is illustrated in the case of the main QRs for arbitrary potentials. In this
      case, which is shown to be precisely described by the linear kicked rotor, exact
      formulas are derived for the diffusion coefficients determining the asymptotic
      evolution of the average kinetic energy of either an incoherent mixture of plane
      waves or a general wave packet. The momentum probability distribution is exactly
      calculated and studied for a two-harmonic potential. It clearly exhibits
      additional resonant values of the quasimomentum and it is robust under small
      deviations from QR.

PMID- 16605429
TI  - Stickiness in Hamiltonian systems: from sharply divided to hierarchical phase
      space.
AB  - We investigate the dynamics of chaotic trajectories in simple yet physically
      important Hamiltonian systems with nonhierarchical borders between regular and
      chaotic regions with positive measures. We show that the stickiness to the border
      of the regular regions in systems with such a sharply divided phase space occurs
      through one-parameter families of marginally unstable periodic orbits and is
      characterized by an exponent gamma=2 for the asymptotic power-law decay of the
      distribution of recurrence times. Generic perturbations lead to systems with
      hierarchical phase space, where the stickiness is apparently enhanced due to the
      presence of infinitely many regular islands and Cantori. In this case, we show
      that the distribution of recurrence times can be composed of a sum of
      exponentials or a sum of power laws, depending on the relative contribution of
      the primary and secondary structures of the hierarchy. Numerical verification of
      our main results are provided for area-preserving maps, mushroom billiards, and
      the newly defined magnetic mushroom billiards.

PMID- 16605430
TI  - Detecting synchronization of self-sustained oscillators by external driving with
      varying frequency.
AB  - We propose a method for detecting the presence of a synchronization of a self
      sustained oscillator by external driving with linearly varying frequency. The
      method is based on a continuous wavelet transform of the signals of the self
      sustained oscillator and external force and allows one to distinguish the case of
      true synchronization from the case of spurious synchronization caused by linear
      mixing of the signals. We apply the method to a driven van der Pol oscillator and
      to experimental data of human heart rate variability and respiration.

PMID- 16605431
TI  - X-wave solutions of complex Ginzburg-Landau equations.
AB  - A solution in the form of X-wave patterns of the complex Ginzburg-Landau equation
      with a harmonic background inhomogeneity is obtained. The pattern can be
      attributed to the effects of the harmonic potential and the boundary
      configuration and size. By varying the harmonic of the background potential, the
      competition among three types of wave patterns: spiral, X, and target, is
      investigated by following the evolution of the Fourier modes.

PMID- 16605432
TI  - Electric field induced instabilities: waves and stationary patterns.
AB  - We examine a prototypical ionic reaction-diffusion system involving the well
      known iodate-arsenous acid reaction in an electric field at a constant current
      density. By taking into consideration of the spatial inhomogeneities in electric
      field intensity and charge density due to ionic migration and diffusion using
      charge balance condition, we look for the different instability regions in the
      appropriate parameter space. We show that the model admits of both absolute and
      convective instability resulting in the development of propagating waves and also
      stationary spatial patterns at times.

PMID- 16605433
TI  - Drift of particles in self-similar systems and its Liouvillian interpretation.
AB  - We study the dynamics of classical particles in different classes of spatially
      extended self-similar systems, consisting of (i) a self-similar Lorentz billiard
      channel, (ii) a self-similar graph, and (iii) a master equation. In all three
      systems, the particles typically drift at constant velocity and spread
      ballistically. These transport properties are analyzed in terms of the spectral
      properties of the operator evolving the probability densities. For systems (i)
      and (ii), we explain the drift from the properties of the Pollicott-Ruelle
      resonance spectrum and corresponding eigenvectors.

PMID- 16605434
TI  - Robust synchronization in fiber laser arrays.
AB  - Synchronization of coupled fiber lasers has been reported in recent experiments
      [Bruesselbach, Opt. Lett. 30, 1339 (2005); Minden, Proc. SPIE 5335, 89 (2004)].
      While these results may lead to dramatic advances in laser technology, the
      mechanism by which these lasers synchronize is not understood. We analyze a
      recently proposed [Rogers, IEEE J. Quantum Electron. 41, 767 (2005)] iterated map
      model of fiber laser arrays to explore this phenomenon. In particular, we look at
      synchronous solutions of the maps when the gain fields are constant. Determining
      the stability of these solutions is analytically tractable for a number of
      different coupling schemes. We find that in the most symmetric physical
      configurations the most symmetric solution is either unstable or stable over
      insufficient parameter range to be practical. In contrast, a lower symmetry
      configuration yields surprisingly robust coherence. This coherence persists
      beyond the pumping threshold for which the gain fields become time dependent.

PMID- 16605435
TI  - Power spectrum characterization of the Anderson transition.
AB  - We examine the power spectrum of the energy level fluctuations of a family of
      critical power-law random banded matrices whose spectral properties are similar
      to those of a disordered conductor at the Anderson transition. It is shown
      analytically and numerically that at the Anderson transition the power spectrum
      presents 1/f2 noise for small frequencies but 1/f noise for larger frequencies.
      The analysis of the region between these two power-law limits gives an accurate
      estimation of the Thouless energy of the system. Finally we discuss in what
      circumstances these findings may be relevant in the case of nonrandom
      Hamiltonians.

PMID- 16605436
TI  - Detecting and characterizing phase synchronization in nonstationary dynamical
      systems.
AB  - We propose a general framework for detecting and characterizing phase
      synchronization from noisy, nonstationary time series. For detection, we propose
      to use the average phase-synchronization time and show that it is extremely
      sensitive to parameter changes near the onset of phase synchronization. To
      characterize the degree of temporal phase synchronization, we suggest to monitor
      the evolution of phase diffusion from a moving time window and argue that this
      measure is practically useful as it can be enhanced by increasing the size of the
      window. While desynchronization events can be caused by either a lack of
      sufficient deterministic coupling or noise, we demonstrate that the time scales
      associated with the two mechanisms are quite different. In particular, noise
      induced desynchronization events tend to occur on much shorter time scales. This
      allows for the effect of noise on phase synchronization to be corrected in a
      practically doable manner. We perform a control study to substantiate these
      findings by constructing and investigating a prototype model of nonstationary
      dynamical system that consists of coupled chaotic oscillators with time-varying
      coupling parameter.

PMID- 16605437
TI  - Spatiotemporal consequences of relaxation time scales in threshold-coupled
      systems.
AB  - We study a class of models incorporating threshold-activated coupling on a
      lattice of chaotic elements. In such systems, the relaxation time allowed between
      chaotic updates determines the intrinsic driving rate due to the local chaos, and
      we show that there exists an inverse cascade from fixed spatial profiles to
      spatiotemporal chaos, as the relaxation time grows shorter. We analyze how this
      spectrum of spatiotemporal transitions arises from the competing time scales of
      the local chaos and the propagation of coupling.

PMID- 16605438
TI  - Noise-memory induced excitability and pattern formation in oscillatory neural
      models.
AB  - We report a noise-memory induced phase transition in an array of oscillatory
      neural systems, which leads to the suppression of synchronous oscillations and
      restoration of excitable dynamics. This phenomenon is caused by the systematic
      contributions of temporally correlated parametric noise, i.e., possessing a
      memory, which stabilizes a deterministically unstable fixed point. Changing the
      noise correlation time, a reentrant phase transition to noise-induced
      excitability is observed in a globally coupled array. Since noise-induced
      excitability implies the restoration of the ability to transmit information,
      associated spatiotemporal patterns are observed afterwards. Furthermore, an
      analytic approach to predict the systematic effects of exponentially correlated
      noise is presented and its results are compared with the simulations.

PMID- 16605439
TI  - Canard orbits in Fabry-Perot cavities induced by radiation pressure and
      photothermal effects.
AB  - A theoretical study of a high-finesse Fabry-Perot cavity considering radiation
      pressure and photothermal displacement is reported. We show that the competition
      between these two effects induces a different kind of dynamic behavior in such a
      system, consisting of canard orbits and excitability. The transition between the
      excitable regime and the canard oscillations, occurring through a supercritical
      Hopf bifurcation, appears in an order compatible with the van der Pol-FitzHugh
      Nagumo equations. Besides its interest as a study of general nonlinear dynamics,
      the characterization of the effects described is critical for high sensitivity
      interferometric displacement measurements as those employed for gravitational
      waves detection.

PMID- 16605440
TI  - Nonlocal coupling can prevent the collapse of spatiotemporal chaos.
AB  - Spatiotemporal chaos on a regular ring network of excitable Gray-Scott dynamical
      elements is transient. We find that the addition of very few nonlocal network
      connections drastically changes the average lifetime of spatiotemporal chaos. In
      the presence of a single shortcut local interface formation delays the collapse
      of spatiotemporal chaos. This competes with a reduced average characteristic path
      length that advances the collapse process. Two added shortcuts can prevent the
      collapse of spatiotemporal chaos by causing an asymptotic local collapse.

PMID- 16605441
TI  - Observation of chaotic itinerancy in the light and carrier dynamics of a
      semiconductor laser with optical feedback.
AB  - We report a direct experimental observation of chaotic itinerancy in simultaneous
      measurements of the light intensity and voltage fluctuations of a laser diode
      exhibiting low-frequency fluctuations. The distribution of trajectories leading
      up to (following) an intensity dropout is computed from the experiment and
      reveals the presence of itinerant mechanisms before (after) dropout initiation. A
      phase space reconstruction of the trajectory for the optimal path of motion
      illustrates sudden shifts between low-dimensional attractor ruins and is shown to
      correspond to simulations of the laser intensity and carrier number.

PMID- 16605442
TI  - Noise-stabilized random attractor.
AB  - A two-dimensional flow model is introduced with deterministic behavior consisting
      of bursts that become successively larger, with longer interburst time intervals
      between them. The system is symmetric in one variable and there are bursts on
      either side of , separated by the presence of an invariant manifold at . In the
      presence of arbitrarily small additive noise in the direction, the successive
      bursts have bounded amplitudes and interburst intervals. This system with noise
      is proposed as a model for edge-localized modes in tokamaks. With noise, the
      bursts can switch from positive to negative and vice versa. The probability
      distribution of burst heights and interburst periods is studied, as is the
      dependence of the statistics on the noise variance. The modification of this
      behavior as the symmetry in is broken is studied, showing qualitatively similar
      behavior if the symmetry breaking is small enough. Experimental observations of a
      nonlinear circuit governed by the same equations are presented, showing good
      agreement.

PMID- 16605443
TI  - Stiff three-frequency orbit of the hydrogen atom.
AB  - We study a stiff quasiperiodic orbit of the electromagnetic two-body problem of
      Dirac's electrodynamics of point charges. The delay equations of motion are
      expanded about circular orbits to obtain the variational equations up to
      nonlinear terms. The three-frequency orbit involves two harmonic modes of the
      variational dynamics with a period of the order of the time for light to travel
      the interparticle distance. In the atomic magnitude, these harmonic modes have a
      frequency that is fast compared with the circular rotation. The quasiperiodic
      orbit has three frequencies: the frequency of circular rotation (slow) and the
      two fast frequencies of two mutually orthogonal harmonic modes. Poynting's
      theorem gives a mechanism for a beat of the mutually orthogonal fast modes to
      cancel the radiation of the unperturbed circular motion by interference. The
      nonradiation condition for this destructive interference is that the two fast
      frequencies beat at the circular frequency. The resonant orbits have magnitudes
      in qualitative and quantitative agreement with quantum electrodynamics (QED), as
      follows: (i) the orbital angular momenta are integer multiples of Planck's
      constant to a good approximation, (ii) the orbital frequencies agree with a
      corresponding emission line of QED within a few percent on average, (iii) the
      orbital frequencies are given by a difference of two linear eigenvalues, viz.,
      the frequencies of the mutually orthogonal fast modes, and (iv) the angular
      momentum of gyration of the variational motion about a resonant circular orbit is
      of the order of Planck's constant.

PMID- 16605444
TI  - Weak-link synchronization.
AB  - We describe a mutual synchronization mechanism observed in a model of fiber laser
      arrays. Though suboptimal in terms of total coherent power, the weak-link
      synchronized state is far more robust than the in-phase state of a uniformly
      pumped array, with respect to parameter mismatch among the individual elements.
      We find similar dynamical behavior in a more general system of coupled
      oscillators where the amplitude dynamics is crucial.

PMID- 16605445
TI  - Stability of wave-packet dynamics under perturbations.
AB  - We introduce a method to investigate the stability of wave-packet dynamics under
      perturbations of the Hamiltonian. Our approach relies on semiclassical
      approximations, but is nonperturbative. Two separate contributions to the quantum
      fidelity are identified: one factor derives from the dispersion of the wave
      packets, whereas the other factor is determined by the separation of a trajectory
      of the perturbed classical system away from a corresponding unperturbed
      trajectory. We furthermore estimate both contributions in terms of classical
      Lyapunov exponents and find a decay of fidelity that is, generically, at least
      exponential, but may also be doubly exponential. The latter case is shown to be
      realized for inverted harmonic oscillators.

PMID- 16605446
TI  - Destruction of spiral waves in chaotic media.
AB  - Spiral-wave breakup in strongly chaotic media with nonphase-coherent chaotic
      attractors is investigated. Spiral-wave dynamics is studied for the Rossler
      reaction diffusion equation as the local attractor changes from a phase-coherent
      to a funnel form. Stable spiral waves with an Archimedean structure are observed
      to persist even when the local chaotic attractor has a funnel form. The
      destruction of funnel spiral waves in strongly chaotic media is induced by the
      strong phase disturbance of the local nonlinear chaotic dynamics, which breaks
      the stable Archimedean spiral structure and globally destroys the spatial
      pattern.

PMID- 16605447
TI  - Self-organized propagation patterns from dynamic self-assembly in monolayers.
AB  - Propagation of localized orientational waves, as imaged by Brewster angle
      microscopy, is induced by low intensity linearly polarized light inside
      axisymmetric smectic-C confined domains in a photosensitive molecular thin film
      at the air/water interface (Langmuir monolayer). Results from numerical
      simulations of a model that couples photoreorientational effects and long-range
      elastic forces are presented. Differences are stressed between our scenario and
      the paradigmatic wave phenomena in excitable chemical media.

PMID- 16605448
TI  - Lattice-Boltzmann method for simulating spherical bubbles with no tangential
      stress boundary conditions.
AB  - A lattice-Boltzmann boundary rule has been developed to recover the slip boundary
      condition at a liquid-gas interface. This rule enables one to use a single
      component lattice-Boltzmann model to simulate bubbly flows where bubbles are
      nearly spherical and coalescence is prohibited. Numerical tests showed this
      method to be robust and accurate in simulating both steady and unsteady flows
      around spherical bubbles in the Reynolds number range 0<Re<30.

PMID- 16605449
TI  - Finite-size effects on open chaotic advection.
AB  - We study the effects of finite-sizeness on small, neutrally buoyant, spherical
      particles advected by open chaotic flows. We show that, when observed in the
      configuration or physical space, the advected finite-size particles disperse
      about the unstable manifold of the chaotic saddle that governs the passive
      advection. Using a discrete-time system for the dynamics, we obtain an expression
      predicting the dispersion of the finite-size particles in terms of their Stokes
      parameter at the onset of the finite-size induced dispersion. We test our theory
      in a system derived from a flow and find remarkable agreement between our
      expression and the numerically measured dispersion.

PMID- 16605450
TI  - Asymptotic freedom, non-Gaussian perturbation theory, and the application of
      renormalization group theory to isotropic turbulence.
AB  - A model equation with an extended range of asymptotic freedom is used as the
      basis of a non-Gaussian perturbation expansion in powers of the control parameter
      of the conditional average. Re-expansion in the local Reynolds number allows the
      systematic rederivation of an earlier, heuristic theory [W. D. McComb and A. G.
      Watt, Phys. Rev. Lett. 65, 3281 (1990)].

PMID- 16605451
TI  - Vortex core dynamics and singularity formations in incompressible Richtmyer
      Meshkov instability.
AB  - Motion of a fluid interface in Richtmyer-Meshkov instability is examined as a
      vortex sheet with the use of Birkhoff-Rott equation. This equation coupled with
      an evolution equation of the strength of the vortex sheet can describe all
      inviscid and incompressible fluid instabilities, i.e., Kelvin-Helmholtz, Rayleigh
      Taylor, and Richtmyer-Meshkov instabilities, when Atwood numbers and initial
      distribution of vorticities are given. With these equations, detailed motion of a
      vortex core in the Richtmyer-Meshkov instability is investigated. For the Kelvin
      Helmholtz and Rayleigh-Taylor instabilities, it is known that the curvature of a
      vortex sheet diverges at a finite time t=tc. This fact indicates that the
      solution loses its analyticity at tc. We show that the singularity formation also
      occurs in the Richtmyer-Meshkov instability and at the same time, accumulation of
      vorticity to some points where singularities are formed develops to the roll-up
      of a sheet when the sheet is regularized. We investigate motion of these
      accumulation points, i.e., vortex cores, and present that their trajectories and
      the strengths depend on the Atwood numbers.

PMID- 16605452
TI  - Effective permeability of porous media containing branching channel networks.
AB  - We study the effective permeability of two-dimensional binary systems
      characterized by a network of branching channels embedded in a uniform matrix
      material. Channels are assigned a higher permeability than the surrounding matrix
      and, therefore, serve as preferential pathways for fluid migration. The channel
      networks are constructed using a nonlooping invasion percolation model. We
      perform extensive numerical flow simulations to determine the effective
      permeability tensor of channel-matrix systems with broadly varying network
      properties. These computed effective permeabilities are then used to
      systematically investigate the factors that control the permeability upscaling
      process. The upscaling framework adopted for this study is based on spatial power
      averaging. We determine the scaling behavior of the averaging exponent omega by
      analyzing its dependence on three characteristic properties of the channel-matrix
      system: (i) the channel-matrix permeability contrast; (ii) the fractal dimension
      of the channel network, df; and (iii) the average tortuosity of spanning paths on
      the network backbone, tau. The behavior of and the corresponding component of
      effective permeability in each principal direction (parallel and perpendicular to
      the network-spanning direction) are compared. The permeability anisotropy ratio
      is shown to be a clear function of key system properties.

PMID- 16605453
TI  - Cluster evolution in steady-state two-phase flow in porous media.
AB  - We report numerical studies of the cluster development of two-phase flow in a
      steady-state environment of porous media. This is done by including biperiodic
      boundary conditions in a two-dimensional flow simulator. Initial transients of
      wetting and nonwetting phases that evolve before steady state has occurred,
      undergo a crossover where every initial pattern is broken up. For flow dominated
      by capillary effects with capillary numbers in order of 10(-5), we find that
      around a critical saturation of nonwetting fluid the nonwetting clusters of size
      have a power-law distribution ns similar to s(-tau)with the exponent tau=1.92+/
      0.04 for large clusters. This is a lower value than the result for ordinary
      percolation. We also present scaling relation and time evolution of the structure
      and global pressure.

PMID- 16605454
TI  - Instability of creeping flow past a deformable wall: the role of depth-dependent
      modulus.
AB  - Linear stability analysis is carried out to examine the effect of a depth
      dependent modulus on the stability of creeping flow of a Newtonian fluid past an
      incompressible and impermeable linear elastic solid. Two different systems are
      considered: (i) Couette flow past a solid with a continuously varying modulus,
      and (ii) Couette flow past two adjacent solids with different thicknesses and
      moduli. For the first system, we find that between two configurations having the
      same average modulus, the more stable configuration is the one that has the
      higher modulus at the interface. In the case of two different configurations
      having the same interfacial modulus and the same average modulus, the more stable
      configuration is the one that has the higher modulus right below the interface.
      For the second system, we find that stability depends in a non-monotonic way on
      the modulus ratio (top modulus to bottom modulus) of the two solids. If the
      thickness of the top solid is less than a critical value, then increasing the
      modulus ratio initially causes the system to be less stable. Since this critical
      thickness decreases as the modulus ratio increases, increasing the modulus ratio
      beyond a certain point causes the system to be more stable. An analysis of the
      solid-solid interfacial boundary conditions suggests that the relationship
      between the stiffness of the top solid and the stability of the system is due to
      a jump in the base-state displacement gradient at the interface which creates a
      net perturbation displacement.

PMID- 16605455
TI  - Energy flux fluctuations in a finite volume of turbulent flow.
AB  - The flux of turbulent kinetic energy from large to small spatial scales is
      measured in a small domain of varying size . The probability distribution
      function of the flux is obtained using a time-local version of Kolmogorov four
      fifths law. The measurements, made at a moderate Reynolds number, show frequent
      events where the flux is backscattered from small to large scales, their
      frequency increasing as is decreased. The observations are corroborated by a
      numerical simulation based on the motion of many particles and on an explicit
      form of the eddy damping.

PMID- 16605456
TI  - Similarity-based constitutive relations for local mass fluxes in incompressible
      mixing layers.
AB  - The local concentrations of the two fluids within a mixing layer produced by an
      interfacial instability are determined by their individual continuity equations.
      Solution of these equations requires constitutive relations for the local mass
      fluxes of the two fluids. We derive explicit analytical expressions for these
      fluxes in planar incompressible mixing layers characterized by a single integral
      length scale h(t), which is presumed to be provided by a suitable mix or
      turbulence model. Elementary scaling arguments imply that in mixing layers of
      this type, the mean volume fraction profile alpha(x,t) depends on x and t only
      through the similarity variable s=x/h(t). The continuity equations determine
      alpha(s) in terms of the mass fluxes. We invert this relationship to obtain
      constitutive relations for the mass fluxes in terms of an arbitrary given
      alpha(s) obtained from experiment or direct numerical simulation. These relations
      can then be employed in more complicated situations (e.g., problems lacking
      spatial symmetry) in which the volume fraction is not known a priori. The
      resulting mass fluxes are not inherently diffusional in character, but can be
      transformed into an alternative equivalent diffusional form that may be
      advantageous for computational purposes. These results are further generalized to
      the case in which the light and heavy regions of the mixing layer exhibit
      different piecewise self-similar scaling behavior characterized by two
      independent integral length scales h1(t) h2(t) and that depend differently on
      time. The validity and practical utility of the formulation are confirmed by a
      test calculation.

PMID- 16605457
TI  - Static configurations and nonlinear waves in rotating nonuniform self-gravitating
      fluids.
AB  - The equilibrium states and low-frequency waves in rotating nonuniform self
      gravitating fluids are studied. The effect of a central object is included. Two
      dimensional static configurations accounting for self-gravity, external gravity,
      and nonuniform rotation are considered for three models connecting the pressure
      with the mass density: thermodynamic equilibrium, polytropic pressure, and
      constant mass density. Explicit analytical solutions for equilibrium have been
      found in some cases. The low-frequency waves arising due to the vertical and
      horizontal fluid inhomogeneities are considered in the linear and nonlinear
      regimes. The relationship between the background pressure and mass density is
      supposed to be arbitrary in the wave analysis. It is shown that the waves
      considered can be unstable in the cases of polytropic pressure and constant mass
      density. The additional nonlinear term proportional to the product of the
      pressure and mass density perturbations, which is usually omitted, is kept in our
      nonlinear equations. There have been found conditions for this term to be
      important. Stationary nonlinear wave equations having solutions in the form of
      coherent vortex structures are obtained in a general form. The importance of
      involving real static configurations in the consideration of wave perturbations
      is emphasized.

PMID- 16605458
TI  - Convective nature of the planimetric instability in meandering river dynamics.
AB  - The convective nature of the linear instability of meandering river dynamics is
      analytically demonstrated and the corresponding Green's function is derived. The
      wave packet due to impulsive disturbance migrates along a river either downstream
      or upstream, depending on the subresonant or superresonant conditions. The
      influence of the parameters that govern the meandering process is shown and the
      role of the fluid dynamic detail used to describe the morphodynamic problem is
      discussed. A numerical simulation of the river planimetry is also developed.

PMID- 16605459
TI  - Effects of target plasma electron-electron collisions on correlated motion of
      fragmented protons.
AB  - The objective of the present work is to examined the effects of plasma target
      electron-electron collisions on H2 + protons traversing it. Specifically, the
      target is deuterium in a plasma state with temperature Te=10 eV and density
      n=10(23) cm(-3), and proton velocities are vp=vth, vp=2vth, and vp=3vth, where
      vth is the electron thermal velocity of the target plasma. Proton interactions
      with plasma electrons are treated by means of the dielectric formalism. The
      interactions among close protons through plasma electronic medium are called
      vicinage forces. It is checked that these forces always screen the Coulomb
      explosions of the two fragmented protons from the same H2 + ion decreasing their
      relative distance. They also align the interproton vector along the motion
      direction, and increase the energy loss of the two protons at early dwell times
      while for longer times the energy loss tends to the value of two isolated
      protons. Nevertheless, vicinage forces and effects are modified by the target
      electron collisions. These collisions enhance the calculated self-stopping and
      vicinage forces over the collisionless results. Regarding proton correlated
      motion, when these collisions are included, the interproton vector along the
      motion direction overaligns at slower proton velocities (vp=vth) and misaligns
      for faster ones (vp=2vth, vp=3vth). They also contribute to a great extend to
      increase the energy loss of the fragmented H2 + ion. This later effect is more
      significant in reducing projectile velocity.

PMID- 16605460
TI  - Improvement of electron beam quality in optical injection schemes using negative
      plasma density gradients.
AB  - Enhanced electron trapping using plasma density down-ramps as a method for
      improving the performance of laser injection schemes is proposed and analyzed. A
      decrease in density implies an increase in plasma wavelength, which can shift a
      relativistic electron from the defocusing to the focusing region of the
      accelerating wakefield, and a decrease in wake phase velocity, which lowers the
      trapping threshold. The specific method of two-pulse colliding pulse injector is
      examined in detail using a three-dimensional test particle tracking code. A
      density down-ramp with a change of density on the order of tens of percent over
      distances greater than the plasma wavelength leads to an enhancement of charge by
      two orders in magnitude or more, up to the limits imposed by beam loading. The
      accelerated bunches are ultrashort (fraction of the plasma wavelength--e.g.,
      approximately 5 fs), high charge ( > 20 pC at modest injection laser intensity
      approximately 10(17) W/cm(2)), with a relative energy spread of a few percent at
      a mean energy of approximately 25 MeV, and a normalized root-mean-square
      emittance of the order of 0.5 mm mrad.

PMID- 16605461
TI  - Ordered spatial structures of dust grains in the thermal plasma.
AB  - The thermal complex plasma of atmospheric pressure, containing the grains of
      condensed phase, has been studied. It has been demonstrated that the existence of
      the space charge areas around the dust grains leads to the inhomogeneous
      ionization of the plasma and the occurrence of the fluxes of nonequilibrium
      charge carriers. These fluxes change the pressure of the gas on the grain
      surfaces and define the forces that force the grains to move towards the zone of
      maximum ionization perturbation of the plasma. It has been shown that the
      combined operation of the electrical forces and the forces of the interface
      pressure leads to the formation of the ordered structures, corresponding to the
      balance of forces. The results of computer simulation, corresponding to the
      experimental data, are given.

PMID- 16605462
TI  - Diffusion of test particles in stochastic magnetic fields for small Kubo numbers.
AB  - Motion of charged particles in a collisional plasma with stochastic magnetic
      field lines is investigated on the basis of the so-called A-Langevin equation.
      Compared to the previously used A-Langevin model, here finite Larmor radius
      effects are taken into account. The A-Langevin equation is solved under the
      assumption that the Lagrangian correlation function for the magnetic field
      fluctuations is related to the Eulerian correlation function (in Gaussian form)
      via the Corrsin approximation. The latter is justified for small Kubo numbers.
      The velocity correlation function, being averaged with respect to the stochastic
      variables including collisions, leads to an implicit differential equation for
      the mean square displacement. From the latter, different transport regimes,
      including the well-known Rechester-Rosenbluth diffusion coefficient, are derived.
      Finite Larmor radius contributions show a decrease of the diffusion coefficient
      compared to the guiding center limit. The case of small (or vanishing) mean
      fields is also discussed.

PMID- 16605463
TI  - Detailed modeling of hydrocarbon nanoparticle nucleation in acetylene discharges.
AB  - The initial stage of nanoparticle formation and growth in radiofrequency
      acetylene (C2H2) plasmas is investigated by means of a self-consistent one
      dimensional fluid model. A detailed chemical kinetic scheme, containing electron
      impact, ion-neutral, and neutral-neutral reactions, has been developed in order
      to predict the underlying dust growth mechanisms and the most important dust
      precursors. The model considers 41 different species (neutrals, radicals, ions,
      and electrons) describing hydrocarbons (CnHm)containing up to 12 carbon atoms.
      Possible routes for particle growth are discussed. Both positive and negative ion
      reaction pathways are considered, as consecutive anion- and cation-molecule
      reactions seem to lead to a fast build up of the carbon skeleton.

PMID- 16605464
TI  - Analysis of Smith-Purcell free-electron lasers.
AB  - We present an analysis of the beam dynamics in a Smith-Purcell free-electron
      laser (FEL). In this system, an electron beam interacts resonantly with a
      copropagating surface electromagnetic mode near the grating surface. The surface
      mode arises as a singularity in the frequency dependence of the reflection
      matrix. Since the surface mode is confined very close to the grating surface, the
      interaction is significant only if the electrons are moving very close to the
      grating surface. The group velocity of the surface mode resonantly interacting
      with a low-energy electron beam is in the direction opposite to the electron
      beam. The Smith-Purcell FEL is therefore a backward wave oscillator in which, if
      the beam current exceeds a certain threshold known as start current, the optical
      intensity grows to saturation even if no mirrors are employed for feedback. We
      derive the coupled Maxwell-Lorentz equations for describing the interaction
      between the surface mode and the electron beam, starting from the slowly varying
      approximation and the singularity in the reflection matrix. In the linear regime,
      we derive an analytic expression for the start current and calculate the growth
      rate of optical power in time. The analysis is extended to the nonlinear regime
      by performing a one-dimensional time-dependent numerical simulation. Results of
      our numerical calculation compare well with the analytic calculation in the
      linear regime and show saturation behavior in the nonlinear regime. We find that
      a significant amount of power grows in the surface mode due to this interaction.
      Several ways to outcouple this power to freely propagating modes are discussed.

PMID- 16605465
TI  - Two-dimensional solitons in the Gross-Pitaevskii equation with spatially
      modulated nonlinearity.
AB  - We introduce a dynamical model of a Bose-Einstein condensate based on the two
      dimensional Gross-Pitaevskii equation, in which the nonlinear coefficient is a
      function of radius. The model describes a situation with spatial modulation of
      the negative atomic scattering length, via the Feshbach resonance controlled by a
      properly shaped magnetic of optical field. We focus on the configuration with the
      nonlinear coefficient different from zero in a circle or annulus, including the
      case of a narrow ring. Two-dimensional axisymmetric solitons are found in a
      numerical form, and also by means of a variational approximation; for an
      infinitely narrow ring, the soliton is found in an exact form (in the latter
      case, exact solitons are also found in a two-component model). A stability region
      for the solitons is identified by means of numerical and analytical methods. In
      particular, if the nonlinearity is supported on the annulus, the upper stability
      border is determined by azimuthal perturbations; the stability region disappears
      if the ratio of the inner and outer radii of the annulus exceeds a critical value
      . The model gives rise to bistability, as the stationary solitons coexist with
      stable axisymmetric breathers, whose stability region extends to higher values of
      the norm than that of the static solitons. The collapse threshold strongly
      increases with the radius of the inner hole of the annulus. Vortex solitons are
      found too, but they are unstable.

PMID- 16605466
TI  - Spectral density of polychromatic electromagnetic waves.
AB  - We investigate theoretically how the vectorial nature of polychromatic
      electromagnetic fields results in polarization components with different spectral
      characteristics, thus leading to redshifts, blueshifts, and spectral
      distributions with multiple peaks. We discuss how these effects can be used to
      design spatially localized spectra with tailored spectral densities.

PMID- 16605467
TI  - Exact solutions of the derivative nonlinear Schrodinger equation for a nonlinear
      transmission line.
AB  - We consider the derivative nonlinear Schrodinger equation with constant potential
      as a model for wave propagation on a discrete nonlinear transmission line. This
      equation can be derived in the small amplitude and long wavelength limit using
      the standard reductive perturbation method and complex expansion. We construct
      some exact soliton and elliptic solutions of the mentioned equation by
      perturbation of its Stokes wave solutions. We find that for some values of the
      coefficients of the equation and for some parameters of solutions, the graphical
      representations show some kinds of symmetries such as mirror symmetry and
      rotational symmetry.

PMID- 16605468
TI  - Soliton collisions with shape change by intensity redistribution in mixed coupled
      nonlinear Schrodinger equations.
AB  - A different kind of shape changing (intensity redistribution) collision with
      potential application to signal amplification is identified in the integrable 
      coupled nonlinear Schrodinger (CNLS) equations with mixed signs of focusing- and
      defocusing-type nonlinearity coefficients. The corresponding soliton solutions
      for the N=2 case are obtained by using Hirota's bilinearization method. The
      distinguishing feature of the mixed sign CNLS equations is that the soliton
      solutions can both be singular and regular. Although the general soliton solution
      admits singularities we present parametric conditions for which nonsingular
      soliton propagation can occur. The multisoliton solutions and a generalization of
      the results to the multicomponent case with arbitrary N are also presented. An
      appealing feature of soliton collision in the present case is that all the
      components of a soliton can simultaneously enhance their amplitudes, which can
      lead to a different kind of amplification process without induced noise.

PMID- 16605469
TI  - Fresnel equations and the refractive index of active media.
AB  - A class of realizable active media exists for which the refractive index cannot
      be defined as an analytic function in the upper half-plane of complex frequency.
      The conventional definition of the refractive index based on analyticity is
      modified such that it is valid for active media in general, and associated
      Fresnel equations are proved. In certain active media, the presence of a
      "backward" wave, for which both phase velocity and Poynting's vector point
      towards the excitation source, is demonstrated.

PMID- 16605470
TI  - Energy and momentum of light in dielectric media.
AB  - The conservation of energy, linear momentum, and angular momentum of the
      electromagnetic field in linear dielectric media with arbitrary dispersion and
      absorption is studied in the framework of an auxiliary field approach in which
      the electric and magnetic fields are complemented by a material field. This
      material field depends on a continuous variable omega, and describes harmonic
      motions of the charges with eigen frequency omega. It carries an electric dipole
      moment and couples as such to the electric field. The equations of motion of the
      model are equivalent to Maxwell's equations in an arbitrary dispersive and
      absorbing dielectric and imply that several quantities are conserved. These
      quantities may be interpreted as the energy, momentum, and angular momentum of
      the total system, and can be viewed as the sum of the corresponding quantities of
      the field and matter subsystems. The total momentum turns out to be equal to the
      Minkowski momentum plus a dispersive contribution. The total energy and total
      momentum of a wave packet both travel with the group velocity, while the ratio of
      total momentum and total energy is given by the phase velocity.

PMID- 16605471
TI  - Adiabatic passage of light in coupled optical waveguides.
AB  - Adiabatic passage of light in coupled optical waveguides with a curved axis is
      theoretically investigated and shown to bear a close connection with coherent
      population transfer among quantum states of atoms and molecules. In particular,
      the optical analog of stimulated Raman adiabatic passage can be realized in a
      three-waveguide optical directional coupler.

PMID- 16605472
TI  - Localized modes and phonon scattering of a lattice kink.
AB  - We consider a discrete sine-Gordon equation with a phase shift. We analyze the
      stability of a lattice kappa kink which is the ground state of the system. The
      dependence of the localized mode frequency of a kappa kink on the topological
      charge is analyzed numerically and analytically. We show that there is a certain
      range of parameter values for the coupling constant and the phase shift for an
      internal mode to exist. A semianalytical calculation on the existence of an
      internal mode of a fractional kink is presented using the characteristic that a
      long wavelength phonon is perfectly transmitted at the appearance of an internal
      mode. We also briefly discuss another type of fractional kink that exists for any
      value of coupling constant. This fractional kink is stable in the weak coupling
      limit but unstable in the opposite one.

PMID- 16605473
TI  - Defect solitons in photonic lattices.
AB  - Nonlinear defect modes (defect solitons) and their stability in one-dimensional
      photonic lattices with focusing saturable nonlinearity are investigated. It is
      shown that defect solitons bifurcate out from every infinitesimal linear defect
      mode. Low-power defect solitons are linearly stable in lower bandgaps but
      unstable in higher bandgaps. At higher powers, defect solitons become unstable in
      attractive defects, but can remain stable in repulsive defects. Furthermore, for
      high-power solitons in attractive defects, we found a type of Vakhitov-Kolokolov
      (VK) instability which is different from the usual VK instability based on the
      sign of the slope in the power curve. Lastly, we demonstrate that in each
      bandgap, in addition to defect solitons which bifurcate from linear defect modes,
      there is also an infinite family of other defect solitons which can be stable in
      certain parameter regimes.

PMID- 16605474
TI  - Tunability of solitary wave properties in one-dimensional strongly nonlinear
      phononic crystals.
AB  - One-dimensional strongly nonlinear phononic crystals were assembled from chains
      of PTFE (polytetrafluoroethylene) and stainless-steel spheres with gauges
      installed inside the beads. Trains of strongly nonlinear solitary waves were
      excited by impacts. A significant modification of the signal shape and an
      increase of solitary wave speed up to two times (at the same magnitude of dynamic
      contact force) were achieved through a noncontact magnetically induced
      precompression of the chains. The data for the PTFE based chains are presented
      for the first time and the data for the stainless-steel beads chains are extended
      into a range of maximum dynamic forces more than one order of magnitude lower
      than previously reported. Experimental results agreed reasonably well with the
      long-wave approximation and numerical calculations based on the Hertz interaction
      law for particles interactions.

PMID- 16605475
TI  - Propagation of mechanical waves in a one-dimensional nonlinear disordered
      lattice.
AB  - The propagation of transverse waves along a string loaded by masses, each of them
      being fixed to a spring with a quadratic nonlinearity, is studied. After
      presenting the nonlinear model and stating the equation of propagation into a
      lattice with discrete nonlinearities and disorder, we propose a perturbation
      approach to wave propagation in a nonlinear lattice using the Green's function
      formalism. We show how the nonlinearity acts on the propagation into a disordered
      lattice. In the low-frequency approximation, an analytical expression of the
      boundary between the propagative regime and the evanescent one is found.
      Numerical results are compared to the analytical results and phase diagrams are
      proposed in the ordered and disordered cases. A behavior of the transmission
      coefficient is found, on an empirical basis, as a function of the length of the
      lattice and the localization length in the nonlinear case. Finally, a dynamic
      approach is developed and the ordered and disordered cases are addressed. This
      method is based on a finite difference equation and allows the construction of
      the Poincare section describing the propagation of the wave into the lattice.
      This approach distinguishes between the properties of propagation in the lattice
      in a propagative regime and in an evanescent one.

PMID- 16605476
TI  - Strongly nonlinear wave dynamics in a chain of polymer coated beads.
AB  - Strongly nonlinear phononic crystals were assembled from a chain of Parylene-C
      coated steel spheres in a polytetrafluoroethylene holder. This system exhibits
      strongly nonlinear properties and extends the range of materials supporting sonic
      vacuum-type behavior. The combination of a high density core and a soft (low
      elastic modulus) coating ensures a relatively low velocity of wave propagation.
      The bead contact interaction caused by the deformation of the Parylene coating
      can be described by classical nonlinear elastic Hertz theory with an effective
      value of the elastic modulus equal to 15 GPa for the contact interaction.
      Strongly nonlinear solitary waves excited by impacts were investigated
      experimentally and compared to chains composed of uniform steel beads. Fracture
      of the polymer coating was detected under relatively large pulse amplitude.

PMID- 16605477
TI  - Statistical mechanics of histories: a cluster Monte Carlo algorithm.
AB  - We present an efficient computational approach to sample the histories of
      nonlinear stochastic processes. This framework builds upon recent work on casting
      a d-dimensional stochastic dynamical system into a (d+1)-dimensional equilibrium
      system using the path-integral approach. We introduce a cluster algorithm that
      efficiently samples histories and discuss how to include measurements that are
      available into the estimate of the histories. This allows our approach to be
      applicable to the simulation of rare events and to optimal state and parameter
      estimation. We demonstrate the utility of this approach for Phi4 Langevin
      dynamics in two spatial dimensions where our algorithm improves sampling
      efficiency up to an order of magnitude.

PMID- 16605478
TI  - Deconstructing the energy landscape: constraint-based algorithms for folding
      heteropolymers.
AB  - We apply the computational methodology of phase retrieval to the problem of
      folding heteropolymers. The ground state fold of the polymer is defined by the
      intersection of two sets in the configuration space of its constituent monomers:
      a geometrical chain constraint and a threshold constraint on the contact energy.
      A dynamical system is then defined in terms of the projections to these
      constraint sets, such that its fixed points solve the set intersection problem.
      We present results for two off-lattice hydrophobic-polar models: one with only
      rotameric degrees of freedom, and one proposed by Stillinger [Phys. Rev. E 48,
      1469 (1993)] with flexible bond angles. Our phase retrieval inspired algorithm is
      competitive with more established algorithms and even finds lower-energy folds
      for one of the longer polymer chains.

PMID- 16605479
TI  - Construction of an extended invariant for an arbitrary ordinary differential
      equation with its development in a numerical integration algorithm.
AB  - For an arbitrary ordinary differential equation (ODE), a scheme for constructing
      an extended ODE endowed with a time-invariant function is here proposed. This
      scheme enables us to examine the accuracy of the numerical integration of an ODE
      that may itself have had no invariant. These quantities are constructed by
      referring to the Nose-Hoover molecular dynamics equation and its related
      conserved quantity. By applying this procedure to several molecular dynamics
      equations, the conventional conserved quantity individually defined in each
      dynamics can be reproduced in a uniform, generalized way; our concept allows a
      transparent outlook underlying these quantities and ideas. Developing the
      technique, for a certain class of ODEs we construct a numerical integrator that
      is not only explicit and symmetric, but preserves a unit Jacobian for a suitably
      defined extended ODE, which also provides an invariant. Our concept is thus to
      simply build a divergence-free extended ODE whose solution is just a lift-up of
      the original ODE, and to constitute an efficient integrator that preserves the
      phase-space volume on the extended system. We present precise discussions about
      the general mathematical properties of the integrator and provide specific
      conditions that should be incorporated for practical applications.

PMID- 16605480
TI  - Lattice Boltzmann method for incompressible flows with large pressure gradients.
AB  - Conventional lattice Boltzmann Bhatnagar-Gross-Krook (LBGK) models can simulate
      incompressible flows correctly only if the Mach number M and the density
      variation deltarho are negligibly small. However, the equation of state p=RTrho
      resulting from the conventional models limits their application to incompressible
      flows with a rather small pressure gradient. In this paper, based on the Enskog
      equation, we propose a finite difference lattice BGK model for isothermal
      incompressible flows with the resulting equation of state and transport
      properties suitable for nonideal fluids. We validated this model by simulating
      the plane Poiseuille flow, the two dimensional Womersley flow, and the backward
      facing step flow and found that the numerical results obtained by the proposed
      model are more accurate than those by the conventional LBGK models when the
      pressure gradient imposed on the flows increases.

PMID- 16605481
TI  - Complete characterization of fourth-order symplectic integrators with extended
      linear coefficients.
AB  - The structure of symplectic integrators up to fourth order can be completely and
      analytically understood when the factorization (split) coefficients are related
      linearly but with a uniform nonlinear proportional factor. The analytic form of
      these extended-linear symplectic integrators greatly simplified proofs of their
      general properties and allowed easy construction of both forward and nonforward
      fourth-order algorithms with an arbitrary number of operators. Most fourth-order
      forward integrators can now be derived analytically from this extended-linear
      formulation without the use of symbolic algebra.

PMID- 16605482
TI  - Remedy for the fermion sign problem in the diffusion Monte Carlo method for few
      fermions with antisymmetric diffusion process.
AB  - We suggest an exact approach to help remedy the fermion sign problem in diffusion
      quantum Monte Carlo simulations. The approach is based on an explicit suppression
      of symmetric modes in the Schrodinger equation by means of a modified stochastic
      diffusion process (antisymmetric diffusion process). We introduce this algorithm
      and illustrate it on potential models in one dimension (1D) and show that there
      it solves the fermion sign problem exactly and converges to the lowest
      antisymmetric state of the system. Then, we discuss extensions of this approach
      to many-dimensional systems on examples of quantum oscillator in 2D-20D and a toy
      model of three and four fermions on harmonic strings in 2D and 3D. We show that
      in all these cases our method shows a performance comparable to that of a fixed
      node approximation with an exact node.

PMID- 16605483
TI  - Hysteretic nonequilibrium Ising-Bloch transition.
AB  - We show that a parametrically driven cubic-quintic complex Ginzburg-Landau
      equation exhibits a hysteretic nonequilibrium Ising-Bloch transition for large
      enough quintic nonlinearity. These results help to understand the recent
      experimental observation of this phenomenon [A. Esteban-Martin, Phys. Rev. Lett.
      94, 223903 (2005)].

PMID- 16605484
TI  - Astonishing life of a coalescing drop on a free surface.
AB  - We report an interesting feature in the consecutive steps of coalescing of a
      drop, which is called a cascade of partial coalescence. It is observed that as
      the secondary drop gets smaller, it bounces higher. We show that the capillary
      force is the main driving force for this phenomenon. By using ultra-high-speed
      video, it is revealed that the capillary force at the pinch off pulls the drop to
      the planar interface. The drop bounces off the interface and moves upward until
      it reaches the maximum height. A theory is developed that includes the capillary
      and gravitational forces and predicts this process.

PMID- 16605485
TI  - Existence of solitons in infinite lattice.
AB  - We consider necessary conditions for existence of optical solitons in one
      dimensional nonlinear periodic layered array. We show analytically that in the
      array with the cubic-quintic nonlinearity bistable solitons are possible whereas
      for the Kerr nonlinearity they never exist. We investigate asymptotic behavior of
      the soliton amplitude at infinity. With help of the asymptotic a numerical
      algorithm for searching the solitons may be developed so that finding a soliton
      on finite interval is simultaneously the numerical proof of its existence on
      infinite interval.

PMID- 16605486
TI  - Comment on "temperature dependence of the Casimir effect".
AB  - Recently, Brevik [Phys. Rev. E, 71, 056101 (2005)] adduced arguments against the
      traditional approach to the thermal Casimir force between real metals and in
      favor of one of the alternative approaches. The latter assume zero contribution
      from the transverse electric mode at zero frequency in qualitative disagreement
      with unity as given by the thermal quantum field theory for ideal metals. Those
      authors claim that their approach is consistent with experiments as well as with
      thermodynamics. We demonstrate that these conclusions are incorrect. We show
      specifically that their results are contradicted by four recent experiments and
      also violate the third law of thermodynamics (the Nernst heat theorem).

PMID- 16605487
TI  - Comment on "effect of a polarized hydrogen target on the polarization of a stored
      proton beam".
AB  - Meyer [Phys. Rev. E 50, 1485 (1994)] analyzed the filtering mechanism of
      polarizing a stored beam by scattering from an internal polarized target. We
      noticed in Meyer's derivation of Eq. (4) of that paper that he had added a new
      twist to an old argument [W. Bruckner, Physics with Antiprotons at LEAR in the
      ACOL Era: Proceedings of the Third LEAR Workshop, Tignes, Savoie, France, January
      19-26, 1985 (Editions Frontieres, Gif-sur-Yvette, France, 1985), p. 245] by
      allowing some particles that are spin flipped to be kept in the beam. We show
      that this invalidates the old result and leads to a more complicated expression
      for the buildup of polarization.

PMID- 16605488
TI  - Comment on "stable and unstable vector dark solitons of coupled nonlinear
      Schrodinger equation: application to two-component Bose-Einstein condensates.
AB  - In a recent paper, V. A. Brazhnyi and V. V. Konoto [Phys. Rev. E 72, 026616
      (2005)] investigated the dynamics of vector dark solitons in two-component Bose
      Einstein condensates. In the small amplitude limit, they deduced a coupled
      Korteweg-de Vries equation from the coupled Gross-Pitaevskii equations. They
      found that two branches of (slow and fast) dark solitons corresponding to the two
      branches of the sound waves exist. The slow solitons, corresponding to the lower
      branch of the acoustic wave, appear to be unstable and transform during the
      evolution into the stable fast solitons (corresponding to the upper branch of the
      dispersion law). However, our discussion shows that these results are incorrect.

PMID- 16605489
TI  - Dynamics, dynamic soft elasticity, and rheology of smectic-C elastomers.
AB  - We present a theory for the low-frequency, long-wavelength dynamics of soft
      smectic-C elastomers with locked-in smectic layers. Our theory, which goes beyond
      pure hydrodynamics, predicts a dynamic soft elasticity of these elastomers and
      allows us to calculate the storage and loss moduli relevant for rheology
      experiments as well as the mode structure.

PMID- 16605490
TI  - Surfactant-induced nematic wetting layer at a thermotropic liquid crystal/water
      interface.
AB  - An ellipsometric study of the interface between a thermotropic liquid crystal and
      water near the nematic-isotropic phase transition of the liquid crystal is
      presented. At temperatures above the transition, a nematic wetting layer appears
      at the interface if the water phase contains a surfactant inducing a homeotropic
      alignment of the nematic phase. The detailed behavior is significantly influenced
      by the concentration of the surfactant. The results can be described by a Landau
      model of nematic wetting in which the surfactant concentration tunes the
      magnitude of an ordering interface potential.

PMID- 16605491
TI  - Critical behavior at the isotropic-to-nematic phase transition in a bent-core
      liquid crystal.
AB  - Magnetic birefringence and dynamic light scattering measurements of orientational
      order parameter fluctuations at the isotropic-nematic phase transition of a bent
      core liquid crystal reveal a pretransitional temperature dependence consistent
      with the standard Landau-deGennes mean field theory. However, as follows: the
      transition in the bent-core compound is more weakly first order (TNI-T*
      approximately 0.4 degrees C), the leading Landau coefficient is approximately 30
      times lower, the viscosity associated with nematic order fluctuations is
      approximately 10 times higher, and the density change is approximately 10 times
      lower, than typically observed in calamitic (rod-shaped) liquid crystals. One
      consistent explanation for these anomalies is an optically isotropic phase
      composed of microscopic complexes or "clusters" of bent-core molecules.

PMID- 16605492
TI  - Reversal of bacterial locomotion at an obstacle.
AB  - Recent experiments have shown large-scale dynamic coherence in suspensions of the
      bacterium B. subtilis, characterized by quorum polarity, collective parallel
      swimming of cells. To probe mechanisms leading to this, we study the response of
      individual cells to steric stress, and find that they can reverse swimming
      direction at spatial constrictions without turning the cell body. The
      consequences of this propensity to flip the flagella are quantified by
      measurements of the inward and outward swimming velocities, whose asymptotic
      values far from the constriction show near perfect symmetry, implying that
      "forwards" and "backwards" are dynamically indistinguishable, as with E. coli.

PMID- 16605493
TI  - Intermediate phase in DNA melting.
AB  - We predict a temperature-driven phase transition of DNA below the melting
      transition. The additional, intermediate phase exists for repetitive sequences,
      when the two strands have different lengths. In this phase, the excess bases of
      the longer strand are completely absorbed as bulge loops inside the helical
      region. When the temperature is lowered, the excess bases desorb into overhanging
      ends, resulting in a contour length change. This continuous transition is in many
      aspects analogous to Bose-Einstein condensation. When the sequence is weakly
      disordered, the contour length changes discontinuously with temperature.

PMID- 16605494
TI  - Universality in two-dimensional cellular structures evolving by cell division and
      disappearance.
AB  - The dynamics of two-dimensional cellular networks is written in terms of coupled
      population equations, which describe how the population of s-sided cells is
      affected by cell division and disappearance. In these equations the effect of the
      rest of the foam on the disappearing or dividing cell is treated as a local mean
      field. Under not too restrictive conditions, the equilibrium distribution P(s) of
      cells satisfies a linear difference equation of order two or higher. The
      population equations are asymptotically integrable. The asymptotic integrability
      implies a "universal" distribution P(s) approximately Cs-kZs for large values of
      s, which is also the Boltzmann distribution associated with the maximum entropy
      inference. Asymptotic integrability of the population equations is absent in a
      global mean-field approximation. The importance of short-range topological
      information to control the evolution of foams is thus confirmed.

PMID- 16605495
TI  - Reaction-subdiffusion equations.
AB  - To analyze possible generalizations of reaction-diffusion schemes for the case of
      subdiffusion we discuss a simple monomolecular conversion A --> B. We derive the
      corresponding kinetic equations for the local and concentrations. Their form is
      rather unusual: The parameters of the reaction influence the diffusion term in
      the equation for a component A, a consequence of the non-Markovian nature of
      subdiffusion. The equation for the product contains a term which depends on the
      concentration of A at all previous times. Our discussion shows that reaction
      subdiffusion equations may not resemble the corresponding reaction-diffusion ones
      and are not obtained by a trivial change of the diffusion operator for a
      subdiffusion one.

PMID- 16605496
TI  - Time-dependent diffusion in a random correlated potential.
AB  - Diffusive behavior of a particle in a two-dimensional random correlated potential
      with Gaussian distribution and exponential correlation is investigated via
      Langevin simulation. Our results show that superdiffusion appears only in the
      early period of the time of evolution and there does not exist an intermediate
      time for the occurrence of the whole issue from subdiffusion to superdiffusion.
      Whether the asymptotic situation of the particle could be arrived before the
      simulation stops is strongly influenced by the finite-size effect of the random
      correlated potential simulated. By applying the random correlated potential to
      the decay of a metastable system, we find that the escape rate of a particle is
      decreased by hill effect of the random potential.

PMID- 16605497
TI  - Kardar-Parisi-Zhang equation in the weak noise limit: pattern formation and upper
      critical dimension.
AB  - We extend the previously developed nonperturbative weak noise scheme, applied to
      the noisy Burgers equation in one dimension, to the Kardar-Parisi-Zhang equation
      for a growing interface in arbitrary dimensions. By means of the Cole-Hopf
      transformation we show that the growth morphology can be interpreted in terms of
      dynamically evolving textures of localized growth modes with superimposed
      diffusive modes. In the Cole-Hopf representation the growth modes are static
      solutions to the diffusion equation and the nonlinear Schrodinger equation,
      subsequently boosted to finite velocity by a Galilei transformation. We discuss
      the dynamics of the pattern formation and, briefly, the superimposed linear
      modes. Implementing the stochastic interpretation we discuss kinetic transitions
      and in particular the preliminary scaling properties pertaining to the pair mode
      or dipole sector. In the dipole sector we obtain the Hurst exponent H=(3-d)/(4-d)
      or dynamic exponent Zdip(4-d)/(3-d) for the random walk of growth modes. Below
      d=3 the dipole growth modes show anomalous diffusion, above d=3 the dipole growth
      modes freeze. Finally, applying Derrick's theorem based on constrained
      minimization we show that the upper critical dimension is d=4 in the sense that
      growth modes cease to exist above this dimension.

PMID- 16605498
TI  - Quantum diffusion in biased washboard potentials: strong friction limit.
AB  - Diffusive transport properties of a quantum Brownian particle moving in a tilted
      spatially periodic potential and strongly interacting with a thermostat are
      explored. Apart from the average stationary velocity, we foremost investigate the
      diffusive behavior by evaluating the effective diffusion coefficient together
      with the corresponding Peclet number. Corrections due to quantum effects, such as
      quantum tunneling and quantum fluctuations, are shown to substantially enhance
      the effectiveness of diffusive transport if only the thermostat temperature
      resides within an appropriate interval of intermediate values.

PMID- 16605499
TI  - Exactly solvable disordered sphere-packing model in arbitrary-dimensional
      Euclidean spaces.
AB  - We introduce a generalization of the well-known random sequential addition (RSA)
      process for hard spheres in d-dimensional Euclidean space Rd. We show that all of
      the n-particle correlation functions of this nonequilibrium model, in a certain
      limit called the "ghost" RSA packing, can be obtained analytically for all
      allowable densities and in any dimension. This represents the first exactly
      solvable disordered sphere-packing model in an arbitrary dimension. The fact that
      the maximal density phi (infinity)=1/2d of the ghost RSA packing implies that
      there may be disordered sphere packings in sufficiently high d whose density
      exceeds Minkowski's lower bound for Bravais lattices, the dominant asymptotic
      term of which is 1/2d. Indeed, we report on a conjectural lower bound on the
      density whose asymptotic behavior is controlled by 2-(0.778,65...)d , thus
      providing the putative exponential improvement on Minkowski's 100-year-old bound.
      Our results suggest that the densest packings in sufficiently high dimensions may
      be disordered rather than periodic, implying the existence of disordered
      classical ground states for some continuous potentials.

PMID- 16605500
TI  - Potential energy landscape and finite-state models of array-enhanced stochastic
      resonance.
AB  - Noise and coupling can optimize the response of arrays of nonlinear elements to
      periodic signals. We analyze such array-enhanced stochastic resonance (AESR)
      using finite-state transition rate models. We simply derive the transition rate
      matrices from the underlying potential energy function of the corresponding
      Langevin problem. Our implementation exploits Floquet theory and provides useful
      theoretical and numerical tools. Our framework both facilitates analysis and
      elucidates the mechanism of AESR. In particular, we show how sublinear coupling
      diminishes AESR, but superlinear coupling enhances it.

PMID- 16605501
TI  - First passage time densities in resonate-and-fire models.
AB  - Motivated by the dynamics of resonant neurons we discuss the properties of the
      first passage time (FPT) densities for non-Markovian differentiable random
      processes. We start from an exact expression for the FPT density in terms of an
      infinite series of integrals over joint densities of level crossings, and
      consider different approximations based on truncation or on approximate summation
      of this series. Thus the first few terms of the series give good approximations
      for the FPT density on short times. For rapidly decaying correlations the
      decoupling approximations perform well in the whole time domain. As an example we
      consider resonate-and-fire neurons representing stochastic underdamped or
      moderately damped harmonic oscillators driven by white Gaussian or by Ornstein
      Uhlenbeck noise. We show that approximations reproduce all qualitatively
      different structures of the FPT densities: from monomodal to multimodal densities
      with decaying peaks. The approximations work for the systems of whatever
      dimension and are especially effective for the processes with narrow spectral
      density, exactly when Markovian approximations fail.

PMID- 16605502
TI  - Alignment of rods and partition of integers.
AB  - We study dynamical ordering of rods. In this process, rod alignment via pairwise
      interactions competes with diffusive wiggling. Under strong diffusion, the system
      is disordered, but at weak diffusion, the system is ordered. We present an exact
      steady-state solution for the nonlinear and nonlocal kinetic theory of this
      process. We find the Fourier transform as a function of the order parameter, and
      show that Fourier modes decay exponentially with the wave number. We also obtain
      the order parameter in terms of the diffusion constant. This solution is obtained
      using iterated partitions of the integer numbers.

PMID- 16605503
TI  - Fundamental-measure density functional theory study of the crystal-melt interface
      of the hard sphere system.
AB  - Two versions of the fundamental measure density functionals together with a new
      interfacial density profile parametrization were used to study the hard-sphere
      crystal-melt interface in the framework of the fundamental measure density
      functional theory. The equilibrium interfacial density profiles and interfacial
      free energies were found as a result of minimization of grand canonical potential
      of system with respect to parameters of density profile. We found that the
      average interfacial free energy is about 0.78, which is in reasonable agreement
      with simulation results.

PMID- 16605504
TI  - Dynamic properties in a family of competitive growing models.
AB  - The properties of a wide variety of growing models, generically called X-RD,
      involving the deposition of particles according to competitive processes, such
      that a particle is attached to the aggregate with probability p following the
      mechanisms of a generic model X that provides the correlations and at random
      [random deposition (RD)] with probability (1-p), are studied by means of
      numerical simulations and analytic developments. The study comprises the
      following X models: Ballistic deposition, random deposition with surface
      relaxation, Das Sarma-Tamboronea, Kim-Kosterlitz, Lai-Das Sarma, Wolf-Villain,
      large curvature, and three additional models that are variants of the ballistic
      deposition model. It is shown that after a growing regime, the interface width
      becomes saturated at a crossover time (tx2) that, by fixing the sample size,
      scales with p according to tx2(p) proportional variant p-y (P>0), where is an
      exponent. Also, the interface width at saturation (Wsat) scales as Wsat(p)
      proportional variant p-delta (p>0), where delta is another exponent. It is proved
      that, in any dimension, the exponents delta and y obey the following
      relationship: delta=y beta RD, where beta RD=1/2 is the growing exponent for RD.
      Furthermore, both exponents exhibit universality in the p --> 0 limit. By mapping
      the behavior of the average height difference of two neighboring sites in
      discrete models of type X-RD and two kinds of random walks, we have determined
      the exact value of the exponent delta. When the height difference between two
      neighbouring sites corresponds to a random walk that after walking <n> steps
      returns to a distance from its initial position that is proportional to the
      maximum distance reached (random walk of type A), one has delta=1/2. On the other
      hand, when the height difference between two neighboring sites corresponds to a
      random walk that after <n> steps moves <l> steps towards the initial position
      (random walk of type B), one has delta=1. Finally, by linking four well
      established universality classes (namely Edwards-Wilkinson, Kardar-Parisi-Zhang,
      linear [molecular beam epitaxy (MBE)] and nonlinear MBE) with the properties of
      type A and B of random walks, eight different stochastic equations for all the
      competitive models studied are derived.

PMID- 16605505
TI  - Single file diffusion in macroscopic Wigner rings.
AB  - The single file diffusion in a circular channel of millimetric charged balls is
      studied. The evolution in time of the mean square displacement is shown to be
      subdiffusive, but slower than the powerlike t1/2 behavior observed in circular
      colloidal systems or predicted in one-dimensional infinite systems.

PMID- 16605506
TI  - Superdiffusion in a honeycomb billiard.
AB  - We investigate particle transport in the honeycomb billiard which consists of
      connected channels placed on the edges of a honeycomb structure. The spreading of
      particles is superdiffusive due to the existence of ballistic trajectories which
      we term perfect paths. Simulations give a time exponent of 1.72 for the mean
      square displacement and a starlike, i.e., anisotropic, particle distribution. We
      present an analytical treatment based on the formalism of continuous-time random
      walks and explain the anisotropic distribution under the assumption that the
      perfect paths follow the directions of the six lattice axes. Furthermore, we
      derive a relation between the time exponent and the exponent of the distribution
      function for trajectories close to a perfect path. In billiards with randomly
      distributed channels, conventional diffusion is always observed in the long-time
      limit, although for small disorder transient superdiffusional behavior exists.
      Our simulation results are again supported by an analytical analysis.

PMID- 16605507
TI  - Entropy of seismic electric signals: analysis in natural time under time
      reversal.
AB  - Electric signals have been recently recorded at the Earth's surface with
      amplitudes appreciably larger than those hitherto reported. Their entropy in
      natural time is smaller than that of a "uniform" distribution. The same holds for
      their entropy upon time reversal. Such a behavior, which is also found by
      numerical simulations in fractional Brownian motion time series and in an on-off
      intermittency model, stems from infinitely ranged long range temporal
      correlations and hence these signals are probably seismic electric signal
      activities (critical dynamics). This classification is strikingly confirmed since
      three strong nearby earthquakes occurred (which is an extremely unusual fact)
      after the original submission of the present paper. The entropy fluctuations are
      found to increase upon approaching bursting, which is reminiscent of the behavior
      identifying sudden cardiac death individuals when analyzing their
      electrocardiograms.

PMID- 16605508
TI  - Persistent random walk on a site-disordered one-dimensional lattice: photon
      subdiffusion.
AB  - We study the persistent random walk of photons on a one-dimensional lattice of
      random transmittances. Transmittances at different sites are assumed independent,
      distributed according to a given probability density f(t). Depending on the
      behavior of f(t) near t=0, diffusive and subdiffusive transports are predicted by
      the disorder expansion of the mean square-displacement and the effective medium
      approximation. Monte Carlo simulations confirm the anomalous diffusion of
      photons. To observe photon subdiffusion experimentally, we suggest a dielectric
      film stack for realization of a distribution f(t).

PMID- 16605509
TI  - Macro- and microdefinitions of fragility of hydrogen-bonded glass-forming
      liquids.
AB  - In the present paper, the nature of the fragility of liquids with a developed H
      bond network is investigated. It is shown that the effective activation energy of
      the shear viscosity eta and the fragility parameter defined as m=d log
      eta/d(Tg/T)|t=t+g are immediately connected with the average number nH(T) of the
      H-bond per molecule. The consistency of the macroscopic (m) and the microscopic
      [M=d(u(2)(0)/<u(-->2)>loc)/d(Tg/T)|T=T+8, where <u-->2>loc=<u-->2>anharm - <u-
      >2>harm] definitions of the fragility is established.

PMID- 16605510
TI  - Calculations of accommodation coefficients for diatomic molecular gases.
AB  - A theoretical study of energy and momentum accommodation coefficients and reduced
      force coefficients for molecular gases exchanging energy with surfaces has been
      carried out. The theoretical model uses classical mechanics for describing
      translational and rotational motions while internal molecular vibrational modes
      are treated quantum mechanically. Calculations for diatomic molecular gases are
      compared with recent measurements using hypersonic beams of N2 incident on SiO2
      layers deposited on Kapton substrates. The theory gives good qualitative
      predictions of the behavior of the various accommodation coefficients as
      functions of the available experimentally controllable parameters such as
      incident translational energy, incident beam angle, molecular and surface masses,
      and surface temperature. Quantitative comparisons with measurements for energy
      and normal momentum accommodation indicate that these experiments can be used to
      obtain basic physical information about the molecule-surface interaction such as
      the physisorption potential well depth and the extent of surface roughness.

PMID- 16605511
TI  - Hydrodynamic profiles for an impurity in an open vibrated granular gas.
AB  - The hydrodynamic state of an impurity immersed in a low density granular gas is
      analyzed. Explicit expressions for the temperature and density fields of the
      impurity in terms of the hydrodynamic fields of the gas are derived. It is shown
      that the ratio between the temperatures of the two components, measuring the
      departure from the energy equipartition, only depends on the mechanical
      properties of the particles, being therefore constant in the bulk of the system.
      This ratio plays an important role in determining the density profile of the
      intruder and its position with respect to the gas, since it determines the sign
      of the pressure diffusion coefficient. The theoretical predictions are compared
      with molecular dynamics simulation results for the particular case of the steady
      state of an open vibrated granular system in the absence of macroscopic fluxes,
      and a satisfactory agreement is found.

PMID- 16605512
TI  - Continuum approach to wide shear zones in quasistatic granular matter.
AB  - Slow and dense granular flows often exhibit narrow shear bands, making them ill
      suited for a continuum description. However, smooth granular flows have been
      shown to occur in specific geometries such as linear shear in the absence of
      gravity, slow inclined plane flows and, recently, flows in split-bottom Couette
      geometries. The wide shear regions in these systems should be amenable to a
      continuum description, and the theoretical challenge lies in finding constitutive
      relations between the internal stresses and the flow field. We propose a set of
      testable constitutive assumptions, including rate independence, and investigate
      the additional restrictions on the constitutive relations imposed by the flow
      geometries. The wide shear layers in the highly symmetric linear shear and
      inclined plane flows are consistent with the simple constitutive assumption that,
      in analogy with solid friction, the effective-friction coefficient (ratio between
      shear and normal stresses) is a constant. However, this standard picture of
      granular flows is shown to be inconsistent with flows in the less symmetric split
      bottom geometry--here the effective friction coefficient must vary throughout the
      shear zone, or else the shear zone localizes. We suggest that a subtle dependence
      of the effective-friction coefficient on the orientation of the sliding layers
      with respect to the bulk force is crucial for the understanding of slow granular
      flows.

PMID- 16605513
TI  - Abrupt transition in a sandpile model.
AB  - We present a fixed energy sandpile model which, by increasing the initial energy,
      undergoes, at the level of individual configurations, a discontinuous transition.
      The model is obtained by modifying the toppling procedure in the Bak-Tang
      Wiesenfeld (BTW) [Phys. Rev. Lett. 59, 381 (1987); Phys. Rev. A 38, 364 (1988)]
      rules: the energy transfer from a toppling site takes place only to neighboring
      sites with less energy (negative gradient constraint) and with a time ordering
      (asynchronous). The model is minimal in the sense that removing either of the two
      above-mentioned constraints (negative gradient or time ordering) the abrupt
      transition goes over to a continuous transition as in the usual BTW case.
      Therefore, the proposed model offers a unique possibility to explore at the
      microscopic level the basic mechanisms underlying discontinuous transitions.

PMID- 16605514
TI  - Surface roughness effects in granular matter: influence on angle of repose and
      the absence of segregation.
AB  - We investigate the effect of nanoscale variations in the surface roughness of
      individual particles on macroscale granular flow characteristics. Experiments
      were conducted in circular rotating tumblers with smooth and rough 2 and 3 mm
      steel particles. The smooth beads had a rms surface roughness of approximately 30
      to 60 nm; rough beads had a surface roughness of approximately 240 to 350 nm. The
      dynamic angle of repose for rough particles increased by 10 degrees to 25 degrees
      over that of smooth particles over a wide range of rotation speeds. Even though
      surface roughness affects the angle of repose, we were unable to detect any
      segregation of bidisperse mixtures of rough and smooth particles in the radial
      direction in two-dimensional (2D) tumblers. Furthermore, no axial banding
      segregation occurred in 3D tumblers, both cylindrical and spherical. For mixtures
      of smooth and rough particles, the angle of repose increased monotonically with
      increasing concentration of rough particles. Particle dynamics simulations
      verified that the dependence of the angle of repose on the concentration of rough
      particles can be directly related to the coefficient of friction of the
      particles. Simulations over a broad range of friction parameters failed to induce
      segregation solely from differences in the angle of repose. These results
      indicate that nanoscale surface roughness can affect the flowability and angle of
      repose of granular matter without driving demixing of the bulk granular material.

PMID- 16605515
TI  - Segregation of large granules from close-packed cluster of small granules due to
      buoyancy.
AB  - Segregation of large granules in a vibrofluidized granular bed with inhomogeneous
      granular number density distribution is studied by an event-driven algorithm.
      Simulation results show that the mean vertical position of large granules
      decreases with the increase of the density ration of the large granules to the
      small ones. This conclusion is consistent with the explanation that the net
      pressure due to the small surrounding particle impacts balances the large
      granular weight, and indict that the upward movement of the large granules is
      driven by the buoyancy. The values of temperature, density, and pressure of the
      systems are also computed by changing the conditions such as heating temperature
      on the bottom and restitution coefficient of particles. These results indicate
      that the segregation of large granules also happen in the systems with density
      inversion or even close-packed cluster of particles floating on a low-density
      fluid, due to the buoyancy. An equation of state is proposed to explain the
      buoyancy.

PMID- 16605516
TI  - Jamming of three-dimensional prolate granular materials.
AB  - We have found that the ability of long thin rods to jam into a solidlike state in
      response to a local perturbation depends upon both the particle aspect ratio and
      the container size. The dynamic phase diagram in this parameter space reveals a
      broad transition region separating granular stick-slip and solidlike behavior. In
      this transition region the pile displays both solid and stick-slip behavior. We
      measure the force on a small object pulled through the pile, and find the
      fluctuation spectra to have power law tails with an exponent characteristic of
      the region. The exponent varies from beta=-2 in the stick-slip region to beta=-1
      in the solid region. These values reflect the different origins--granular
      rearrangements vs dry friction--of the fluctuations. Finally, the packing
      fraction shows only a slight dependence on container size, but depends on aspect
      ratio in a manner predicted by mean-field theory and implies an aspect-ratio
      independent contact number of <c>=5.25 +/- 0.03.

PMID- 16605517
TI  - Use of a void network model to correlate porosity, mercury porosimetry, thin
      section, absolute permeability, and NMR relaxation time data for sandstone rocks.
AB  - The Pore-Cor void network model is used to construct stochastic realizations of
      the void structures of five sandstone samples of varying lithography. A close
      match was achieved to experimental porosity and mercury intrusion curves. The
      samples were resin impregnated and the fragments of voids revealed in thin
      sections photographed by backscatter electron microscopy at two magnifications.
      The sizes of these pore fragments matched those derived from a simulated
      microtoming of the network model much more closely than the sizes derived from
      the traditional capillary bundle approximation. Absolute permeabilities of the
      network were calculated by finding the flow capacity of the entire flow network,
      based on parametrized Navier Stokes equations with Klinkenberg correction,
      applied to each pore-throat-pore arc. A match to the experimental trend was
      obtained, although the network model considerably underestimated the experimental
      values. The results were also compared with the semiempirical equations of
      Thomson et al. and Kozeny and Carmen modified to accept thin section image
      analysis. Finally, the simulated pore and throat size distributions were compared
      to proton NMR transverse (T2) spin-echo relaxation times. Although the shapes of
      the distributions differed markedly, the mean values trended together. The
      capillary bundle approximation, however, gave a poor match to the NMR data.

PMID- 16605518
TI  - Impact of boundaries on velocity profiles in bubble rafts.
AB  - Under conditions of sufficiently slow flow, foams, colloids, granular matter, and
      various pastes have been observed to exhibit shear localization, i.e., regions of
      flow coexisting with regions of solidlike behavior. The details of such shear
      localization can vary depending on the system being studied. A number of the
      systems of interest are confined so as to be quasi two-dimensional, and an
      important issue in these systems is the role of the confining boundaries. For
      foams, three basic systems have been studied with very different boundary
      conditions: Hele-Shaw cells (bubbles confined between two solid plates); bubble
      rafts (a single layer of bubbles freely floating on a surface of water); and
      confined bubble rafts (bubbles confined between the surface of water below and a
      glass plate on top). Often, it is assumed that the impact of the boundaries is
      not significant in the "quasistatic limit," i.e., when externally imposed rates
      of strain are sufficiently smaller than internal kinematic relaxation times. In
      this paper, we directly test this assumption for rates of strain ranging from 10(
      3) to 10(-2) s(-1). This corresponds to the quoted rate of strain that had been
      used in a number of previous experiments. It is found that the top plate
      dramatically alters both the velocity profile and the distribution of nonlinear
      rearrangements, even at these slow rates of strain. When a top is present, the
      flow is localized to a narrow band near the wall, and without a top, there is
      flow throughout the system.

PMID- 16605519
TI  - Computer simulation of electrical conductivity of colloidal dispersions during
      aggregation.
AB  - The computation approach to the simulation of electrical conductivity of
      colloidal dispersions during aggregation is considered. We use the two
      dimensional diffusion-limited aggregation model with multiple-seed growth. The
      particles execute a random walk, but lose their mobility after contact with the
      growing clusters or seeds. The two parameters that control the aggregation are
      the initial concentration of free particles in the system p and the concentration
      of seeds psi. The case of psi=1, when all the particles are the immobile seeds,
      corresponds with the usual random percolation problem. The other limiting case of
      psi=0, when all the particles walk randomly, corresponds to the dynamical
      percolation problem. The calculation of electrical conductivity and cluster
      analysis were done with the help of the algorithms of Frank-Lobb and Hoshen
      Kopelman. It is shown that the percolation concentration phi c decreases from
      0.5927 at psi=1 to 0 at psi --> 0. Scaling analysis was applied to study
      exponents of correlation length v and of conductivity t. For all psi>0 this model
      shows universal behavior of classical 2d random percolation with v approximately
      t approximately 4/3. The electrical conductivity sigma of the system increases
      during aggregation reaching up to a maximum at the final stage. The concentration
      dependence of conductivity sigma(phi) obeys the general effective medium equation
      with apparent exponent ta(psi) that exceeds t. The kinetics of electrical
      conductivity changes during the aggregation is discussed. In the range of
      concentration Pc(phi)<p<0.9527 the time of percolation cluster formation pi c
      decreases with increasing phi.

PMID- 16605520
TI  - Double-peaked impact force of very soft gel balls.
AB  - We measure the time change of the contact force F(t) during the impact between
      very soft gel balls and a rigid substrate. For low-impact velocities Vi, F(t) is
      single-peak functions as intuitively expected; and the relation between Vi and
      the peak value Fm [of F(t)] obeys the prediction of the standard theory for the
      impact in the linear elastic regime (i.e., the Hertz theory). On the other hand,
      for large Vi, where the gel ball deforms into thin pancakelike shapes, F(t)
      becomes double-peak functions. We compare the data of F(t) for large Vi with a
      prediction of a model proposed in our previous study [Tanaka, Europhys. J. E 18,
      95 (2005)]. The model can quantitatively reproduce the experimental Fm - Vi
      relation, and shows that the double-peak behavior of F(t) is a consequence of the
      expanding deformation of the pancake-shaped gel, i.e., spreading motion parallel
      to the substrate.

PMID- 16605521
TI  - Simple models of complex aggregation: vesicle formation by soft repulsive spheres
      with dipolelike interactions.
AB  - Structural and thermodynamic properties of spherical particles carrying classical
      spins are investigated by Monte Carlo simulations. The potential energy is the
      sum of short range, purely repulsive pair contributions, and spin-spin
      interactions. These last are of the dipole-dipole form, with however, a crucial
      change of sign. At low density and high temperature the system is a homogeneous
      fluid of weakly interacting particles and short range spin correlations. With
      decreasing temperature particles condense into an equilibrium population of free
      floating vesicles. The comparison with the electrostatic case, giving rise to
      predominantly one-dimensional aggregates under similar conditions, is discussed.
      In both cases condensation is a continuous transformation, provided the isotropic
      part of the interatomic potential is purely repulsive. At low temperature the
      model allows us to investigate thermal and mechanical properties of membranes. At
      intermediate temperatures it provides a simple model to investigate equilibrium
      polymerization in a system giving rise to predominantly two-dimensional
      aggregates.

PMID- 16605522
TI  - Duality and similarity properties of the effective permittivity of two
      dimensional heterogeneous medium with inclusion of fractal geometry.
AB  - We report a systematic finite-difference time-domain study on the dielectric
      properties of two-dimensional lossless heterostructures with inclusion of
      deterministic fractal geometry (Koch's snowflake, Sierpinski's square and
      triangle) constrained to sit in a circumscribed circle, for a wide range of
      surface fractions. In all the configurations investigated, we observed (i) a
      strong deviation of the surface fraction dependence of the effective permittivity
      based on Maxwell Garnett analysis, and (ii) a permittivity change with reduced
      perimeter according to a similarity transformation, at least for the first three
      iterations of the fractal pattern. We show that the results of our numerical
      analysis disagree with expectations from the duality (phase interchange)
      relation, and explain this as being due to the intrinsic complexity of the
      morphology which requires a multipolar approach to correctly describe the
      microstructure features of these heterostructures.

PMID- 16605523
TI  - Ellipsometric light scattering for the characterization of thin layers on
      dispersed colloidal particles.
AB  - The thin interface layer on colloids in a liquid can be characterized by applying
      nulling ellipsometry to a scattering experiment. Close to 90 degrees scattering
      angle the ellipsometric quantities tan(Psi) and Delta of particles smaller than
      the wavelength behave like at the Brewster angle of reflection ellipsometry. The
      minimum of tan(Psi) and the slope of Delta depend on thickness and refractive
      index of the layer, while the location of the minimum is sensitive to the
      refractive index of the particle. As an example, the swelling of a
      thermosensitive layer on colloidal particles has been determined from
      measurements at two wavelengths.

PMID- 16605524
TI  - Scattering for mixtures of hard spheres: comparison of total scattering
      intensities with model.
AB  - The angular dependence of the intensity of x-rays scattered from binary and
      ternary hard sphere mixtures is investigated and compared to the predictions of
      two scattering models. Mixture ratio and total volume fraction dependent effects
      are investigated for size ratios equal to 0.51 and 0.22. Comparisons of model
      predictions with experimental results indicate the significant impact of the role
      of particle size distributions in interpreting the angular dependence of the
      scattering at wave vectors probing density fluctuations intermediate between the
      sizes of the particles in the mixture.

PMID- 16605525
TI  - Dynamic effects on nonlinear alternating current responses in electrorheological
      fluids.
AB  - By using a perturbation approach, we investigate dynamic effects on nonlinear
      alternating current (ac) responses in electrorheological (ER) fluids under an ac
      or direct current electric field. We show that the dynamic effect due to a shear
      flow, which exerts a torque on ER particles and thus leads to the rotation of the
      particles about their centers, plays a significant role in the responses. Our
      results can be well interpreted in the dielectric dispersion spectral
      representation, and they offer a convenient method to determine the relaxation
      time and rotation velocity of ER particles by measuring the nonlinear ac
      responses.

PMID- 16605526
TI  - Low-frequency dynamical heterogeneity in simulated amorphous Ni0.5Zr0.5 below its
      glass temperature: correlations with cage volume and local order fluctuations.
AB  - From molecular dynamics simulations results are reported concerning correlations
      between low-frequency (lf) heterogeneous dynamics in simulated Ni0.5Zr0.5 melts
      at 700, 760, and 810 K, which means around the Kauzmann temperature of the model,
      TK approximately 750 K. A method is presented to separate lf dynamics, reflecting
      the slow relaxation dynamics in the vitrifying melt, and high-frequency (hf)
      dynamics, characteristic of the thermal fluctuations at the considered
      temperatures. By means of a suitable quantitative measure of the distribution of
      heterogeneous lf dynamics in space and time, correlation parameters are evaluated
      between the spatial distribution of lf dynamics and structural inhomogeneities in
      the thermodynamically homogeneous melt. Relevant correlations are found between
      lf dynamics and some involved structure quantities such as the cage volume around
      Ni atoms, Omega Ni, or the Theta Ni parameter which reflects the geometry of the
      nearest-neighbor cage around Ni atoms. Further, at 810 K there is a weak
      correlation between heterogeneous dynamics and fluctuations of the mean potential
      energy per atom and a comparable weak anticorrelation with the particle density
      and Ni-atom density inhomogeneities, where these three correlations decrease with
      decreasing temperature. The present results indicate the existence of long-living
      regions of enhanced Omega Ni in the structure, which may act as regions of
      preferential initiation of irreversible lf dynamics and slow relaxation.

PMID- 16605527
TI  - Symmetry, equivalence, and molecular self-assembly.
AB  - Molecular self-assembly at equilibrium is fundamental to the fields of biological
      self-organization, the development of novel environmentally responsive polymeric
      materials, and nanofabrication. Our approach to understanding the principles
      governing this process is inspired by existing models and measurements for the
      self-assembly of actin, tubulin, and the ubiquitous icosahedral shell structures
      of viral capsids. We introduce a family of simple potentials that give rise to
      the self-assembly of linear polymeric, random surface ("membrane"), tubular
      ("nanotube"), and hollow icosahedral structures that are similar in many respects
      to their biological counterparts. The potentials involve equivalent particles and
      an interplay between directional (dipolar, multipolar) and short-range (van der
      Waals) interactions. Specifically, we find that the dipolar potential, having a
      continuous rotational symmetry about the dipolar axis, gives rise to chain
      formation, while particles with multipolar potentials, having discrete rotational
      symmetries (square quadrupole or triangular ring of dipoles or "hexapole"), lead
      to the self-assembly of open sheet, nanotube, and hollow icosahedral geometries.
      These changes in the geometry of self-assembly are accompanied by significant
      changes in the kinetics of the organization.

PMID- 16605528
TI  - Stress response and structural transitions in sheared gyroidal and lamellar
      amphiphilic mesophases: Lattice-Boltzmann simulations.
AB  - We report on the stress response of gyroidal and lamellar amphiphilic mesophases
      to steady shear simulated using a bottom-up lattice-Boltzmann model for
      amphiphilic fluids and sliding periodic (Lees-Edwards) boundary conditions. We
      study the gyroid per se (above the sponge-gyroid transition, of high
      crystallinity) and the molten gyroid (within such a transition, of shorter-range
      order). We find that both mesophases exhibit shear thinning, more pronounced and
      at lower strain rates for the molten gyroid. At late times after the onset of
      shear, the skeleton of the crystalline gyroid becomes a structure of
      interconnected irregular tubes and toroidal rings, mostly oriented along the
      velocity ramp imposed by the shear, in contradistinction with free-energy
      Langevin-diffusion studies which yield a much simpler structure of disentangled
      tubes. We also compare the shear stress and deformation of lamellar mesophases
      with and without amphiphile when subjected to the same shear flow applied normal
      to the lamellae. We find that the presence of amphiphile allows (a) the shear
      stress at late times to be higher than in the case without amphiphile, and (b)
      the formation of rich patterns on the sheared interface, characterized by
      alternating regions of high and low curvature.

PMID- 16605529
TI  - Simulated structural and thermal properties of glassy and liquid germania.
AB  - Structural, dynamical, and thermal properties of germanium dioxide are
      investigated with classical molecular dynamics simulations from the amorphous to
      the liquid state. Pair correlation functions and coordination numbers are
      computed under pressure change and show the progressive conversion of the
      tetrahedral network into an octahedral network, in agreement with experiments.
      The thermodynamical behavior of the liquid is investigated by means of an
      equation of state that allows a precise estimation of the compressibility. At low
      temperature, the diffusion constant D shows an Arrhenius law that progressively
      deviates when the temperature is increased. The overall comparison with simulated
      silica permits finally to outline not only the differences in the physical
      behavior of these two similar systems but also to stress the limitation of the
      employed germania potential.

PMID- 16605530
TI  - Modeling of droplet breakup in a microfluidic T-shaped junction with a phase
      field model.
AB  - A phase-field method is applied to the modeling of flow and breakup of droplets
      in a T-shaped junction in the hydrodynamic regime where capillary and viscous
      stresses dominate over inertial forces, which is characteristic of microfluidic
      devices. The transport equations are solved numerically in the three-dimensional
      geometry, and the dependence of the droplet breakup on the flow rates, surface
      tension and viscosities of the two components is investigated in detail. The
      model reproduces quite accurately the phase diagram observed in experiments
      performed with immiscible fluids. The critical capillary number for droplet
      breakup depends on the viscosity contrast, with a trend which is analogous to
      that observed for individual isolated droplets in hyperbolic flow.

PMID- 16605531
TI  - Step dynamics on vicinal surfaces using discrete interface models.
AB  - Fluctuations of a single step on a vicinal surface are investigated using a
      discrete model designed to go further in capturing atomistic effects than usually
      achieved with continuum models. Variants of the model to incorporate the
      following three types of adatom dynamics are studied: attachment-detachment;
      periphery (step-edge) diffusion; and terrace diffusion. The dynamic exponent z is
      determined for each type as well as crossover functions joining three distinct
      scaling regimes.

PMID- 16605532
TI  - Roughening and inclination of competition interfaces.
AB  - We study the competition interface between two clusters growing over a random
      vacant sector of the plane in a simple setup which allows us to perform formal
      computations and obtain analytical solutions. We demonstrate that a phase
      transition occurs for the asymptotic inclination of this interface when the final
      macroscopic shape goes from curved to noncurved. In the first case it is random
      while in the second one it is deterministic. We also show that the flat case
      (stationary growth) is a critical point for the fluctuations: for curved and flat
      final profiles the fluctuations are in the Kardar-Parisi-Zhang (KPZ) scale (2/3);
      for noncurve final profile the fluctuations are in the same scale of the
      fluctuations of the initial conditions, which in our model are Gaussian (1/2).

PMID- 16605533
TI  - Tessellation of a stripe.
AB  - This paper describes enumeration of a class of topologically distinct periodic
      divisions of a stripe. Optimization of the geometry of these periodic tilings-
      optimization that yields minimum total perimeter of the tiles--gives a set of
      physically plausible periodic structures of monodisperse, two-dimensional foams
      bounded by two parallel walls. Evaluation of the minimum total perimeters of the
      lattices that we enumerated suggests two possible lower bounds for the mean
      perimeter of tiles forming periodic coverings of a stripe.

PMID- 16605534
TI  - Spinodal decomposition in thin films: molecular-dynamics simulations of a binary
      Lennard-Jones fluid mixture.
AB  - We use molecular dynamics (MD) to simulate an unstable homogeneous mixture of
      binary fluids (AB), confined in a slit pore of width D. The pore walls are
      assumed to be flat and structureless and attract one component of the mixture (A)
      with the same strength. The pairwise interactions between the particles are
      modeled by the Lennard-Jones potential, with symmetric parameters that lead to a
      miscibility gap in the bulk. In the thin-film geometry, an interesting interplay
      occurs between surface enrichment and phase separation. We study the evolution of
      a mixture with equal amounts of A and B, which is rendered unstable by a
      temperature quench. We find that A-rich surface enrichment layers form quickly
      during the early stages of the evolution, causing a depletion of A in the inner
      regions of the film. These surface-directed concentration profiles propagate from
      the walls towards the center of the film, resulting in a transient layered
      structure. This layered state breaks up into a columnar state, which is
      characterized by the lateral coarsening of cylindrical domains. The qualitative
      features of this process resemble results from previous studies of diffusive
      Ginzburg-Landau-type models [S. K. Das, S. Puri, J. Horbach, and K. Binder, Phys.
      Rev. E 72, 061603 (2005)], but quantitative aspects differ markedly. The relation
      to spinodal decomposition in a strictly two-dimensional geometry is also
      discussed.

PMID- 16605535
TI  - Transport theory at the nanoscale. I. Surface waves.
AB  - Small scale particle motion is the cause of dynamic roughening and plays a role
      during film growth. To study surface waves on the molecular level, a continuum
      approach is used that links atomic and macroscopic dynamics though a Fokker
      Planck equation for the distribution of particle trajectories. The dynamic
      equation for the density interfacial profile includes inertia terms indispensable
      for high frequency fluctuations. For wave vectors below the critical value, an
      initial periodic deformation of the surface on the order of the density
      correlation length simply decays with time. Above the critical wave vector,
      collective periodic motion is induced in the interface. A picture of short lived,
      localized high frequency wavelets emerges with contributions from acoustic,
      capillary, and elastic surface modes.

PMID- 16605536
TI  - Transport theory at the nanoscale. II. Interface dynamics for film growth.
AB  - Conditions for surface nucleation and growth of a film are determined in a
      diffuse interface model. A method is given, derived from a Fokker-Planck equation
      for the nonequilibrium particle distribution, which links atomic and mesoscopic
      events in a rheological description similar to the classical continuum theory of
      fluid flow. Film nucleation and growth are modeled by the spatially inhomogeneous
      continuous evolution of the instantaneous density profile which measures the
      average number of particles or molecules at given time and position. It is shown
      how an alteration in the distribution of particles in the vicinity of the
      boundary between parent and product phases induces transient film growth and
      damped vibrations at the surface. The method is general but as an illustration,
      the condensation of a simple classical fluid on cooling is considered in detail.

PMID- 16605537
TI  - Statistical mechanics of nucleation: incorporating translational and rotational
      free energy into thermodynamics of a microdroplet.
AB  - Motivated by the original Lothe-Pound prescription, we derive a formula for the
      replacement partition function that is suitable for vapor to liquid phase
      nucleation in terms of the classical phase integral. The resulting expression was
      evaluated for truncated and shifted Lennard-Jones fluids by means of computer
      simulation. The corresponding Lothe-Pound correction factor, which is to multiply
      the classical expression for the nucleation rate, decreases significantly with
      increasing temperature and decreasing cluster size, and is in the range of 10(9)
      10(13) for the temperatures and the cluster sizes we studied. This is somewhat
      smaller than the original estimate of 10(17) by Lothe and Pound.

PMID- 16605538
TI  - Breath figure templated self-assembly of porous diblock copolymer films.
AB  - Porous polyethylene oxide-b-polyfluorooctylmethacrylate (PEO-b-PFOMA) diblock
      copolymer films were drop cast onto substrates from Freon (1,1,2
      trichlorotrifluoroethane) in a humid atmosphere. The pores in the films exhibit
      long range hexagonal order in some cases, depending on the PFOMA-to-PEO molecular
      weight ratio. Films with the best ordered pores were formed with PFOMA-to-PEO
      ratios of 70 kDa:2 kDa. The pores in the polymer films derive from water droplets
      that condense as Freon evaporates. The polymer stabilizes the water droplets, or
      "breath figures," which act as an immiscible template that molds the porous film.
      Increased polymer hydrophobicity reduces the water wettability of the air/Freon
      interface, which in turn decreases water droplet nucleation, thus influencing the
      final pore size and spatial order in the polymer films. We describe how water
      droplet nucleation influences the final pore size and packing order in the
      polymer films.

PMID- 16605539
TI  - Diffusive atomistic dynamics of edge dislocations in two dimensions.
AB  - The fundamental dislocation processes of glide, climb, and annihilation are
      studied on diffusive time scales within the framework of a continuum field
      theory, the phase field crystal model. Glide and climb are examined for single
      edge dislocations subjected to shear and compressive strain, respectively, in a
      two-dimensional hexagonal lattice. It is shown that the natural features of these
      processes are reproduced without any explicit consideration of elasticity theory
      or ad hoc construction of microscopic Peierls potentials. Particular attention is
      paid to the Peierls barrier for dislocation glide or climb and the ensuing
      dynamic behavior as functions of strain rate, temperature, and dislocation
      density. It is shown that the dynamics are accurately described by simple viscous
      motion equations for an overdamped point mass, where the dislocation mobility is
      the only adjustable parameter. The critical distance for the annihilation of two
      edge dislocations as a function of separation angle is also presented.

PMID- 16605540
TI  - Evolution of light-induced anchoring in dye-doped nematics: experiment and model.
AB  - A series of experiments was carried out to describe the evolution of light
      induced anchoring in dye-doped nematic liquid crystals (LCs) at irradiation with
      polarized light. The experiments included cells filled with a pure pentyl
      cyanobiphenyl (5CB) and containing a layer of azo dye deposited on an aligning
      film, as well as cells filled with azo dye doped 5CB, which allowed us to
      distinguish the role of "surface" and "bulk" dye molecules in the evolution of
      light-induced anchoring. Modifications of the spectra of spontaneously adsorbed
      dye molecules under illumination enabled us to assert that light-induced
      desorption is a mechanism responsible for producing an easy orientation axis in a
      dark-adsorbed layer. We found that the evolution of light-induced anchoring
      involves a competition between light-induced desorption and adsorption of the dye
      molecules on the aligning surface, and the final anchoring is determined by the
      total light irradiation dose. These data allowed introducing a theoretical model
      of light-induced anchoring of dye-doped nematic LCs that quantitatively described
      the experimental results and portrayed the whole evolution of the dye-doped LC
      cell at irradiation.

PMID- 16605541
TI  - Casimir interaction in smectic-A liquid crystals caused by coupled fluctuations
      of positional and orientational order.
AB  - A theoretical study of the Casimir interaction in smectic-A systems, considering
      fluctuations of both types of smectic ordering--positional and orientational-
      including the coupling between them, is presented. Two model systems with plan
      parallel geometry are studied: homeotropic cell and free-standing film. At large
      thicknesses of the system the behavior of the Casimir force is found to be
      primarily determined by positional fluctuations, whereas at small thicknesses
      also the orientational degrees of freedom greatly contribute to the interaction.
      The influence of different coupling strengths between orientational and
      positional order is presented. The dependence of the Casimir force on the
      director anchoring and surface-tension parameters is studied. The possibilities
      of experimental detection of the interaction are discussed.

PMID- 16605542
TI  - Physical mechanism for in-plane molecular orientation in polymer-dispersed
      ferroelectric liquid crystals.
AB  - The physical mechanism of liquid crystal (LC) alignment in ferroelectric LC (FLC)
      droplets dispersed in a photocurable polymer matrix was studied. The
      orientational ordering of both FLC molecules and the polymer matrix was induced
      by a rubbed polyimide alignment layer. There existed an optimum FLC droplet size
      for the production of uniformly oriented molecules and smectic layers for maximum
      electro-optic modulation. The alignment quality was critically dependent on the
      droplet size, shape, the helical pitch, and the phase transition sequence of the
      FLCs. The molecular structure formed inside the FLC droplets resulted from a
      delicate balance between the elastic energy stored in a restricted geometry and
      surface interactions at the FLC-polymer interface.

PMID- 16605543
TI  - Polar order in columnar phase made of polycatenar bent-core molecules.
AB  - Columnar phases made of polycatenar molecules with bent-shaped mesogenic cores
      are studied. The polar order in this system is associated with the change of the
      column building blocks from flat disks (Colh phase) into cones (Colh PA phase),
      which allows for axial polarization of the columns. The nature of the Colh and
      Colh PA phase transition changes from first order for short homologues to
      continuous for the longest one. This can be attributed to decreasing
      intercolumnar interactions due to broadening of the columnar scaffold made of
      partially melted terminal alkyl chains. Decrease of intercolumnar interactions is
      also responsible for a strong increase of the pretransitional fluctuations in the
      Colh phase. The mesophase observed for the longest homologues is reminiscent of
      the relaxor phase observed for solid crystals.

PMID- 16605544
TI  - Complete breakdown of the Debye model of rotational relaxation near the isotropic
      nematic phase boundary: effects of intermolecular correlations in orientational
      dynamics.
AB  - The Debye-Stokes-Einstein (DSE) model of rotational diffusion predicts that the
      orientational correlation times tau l vary as [l(l+1)]-1, where l is the rank of
      the orientational time correlation function (given in terms of the Legendre
      polynomial of rank l). One often finds significant deviation from this
      prediction, in either direction. In supercooled molecular liquids where the ratio
      tau 1/tau 2 falls considerably below 3 (the Debye limit), one usually invokes a
      jump diffusion model to explain the approach of the ratio tau 1/tau 2 to unity.
      Here we show in a computer simulation study of a standard model system for
      thermotropic liquid crystals that this ratio becomes much less than unity as the
      isotropic-nematic phase boundary is approached from the isotropic side.
      Simultaneously, the ratio tau 2/eta, eta, being the shear viscosity of the
      liquid, becomes much larger than the hydrodynamic value near the I-N transition.
      We also analyze the breakdown of the Debye model of rotational diffusion in
      ratios of higher order orientational correlation times. We show that the
      breakdown of the DSE model is due to the growth of orientational pair correlation
      and provide a mode coupling theory analysis to explain the results.

PMID- 16605545
TI  - Spontaneous shears in smectic elastomers.
AB  - We model the spontaneous elastic shear deformations of smectic elastomers as they
      make the thermal transition between the A and C phases. Tilt of the director is
      accompanied by shear. Unlike nematic elastomers where spontaneous elongation is
      associated with changes in the magnitude of order, spontaneous distortion in
      smectics is instead shear and is associated with rotation of the director of the
      underlying nematic order. The effect of the multistage cross-linking associated
      with creating monodomain elastomers is taken into account. The angle of molecular
      tilt and the angle associated with spontaneous shear deformation are not simply
      related.

PMID- 16605546
TI  - Soft-stiff regime crossover for an aerosil network dispersed in liquid crystals.
AB  - Hydrophilic and hydrophobic aerosil particles immersed in S-(+)-[4-(2
      methylbutyl) phenyl 4-n-octylbiphenyl-4-carboxylate] or [p-(n-decyloxy)
      benzylidene-p-amino-(2-methylbutyl) cinnamate] compound have been studied by
      employing x-ray diffraction. The aerosil-induced relative layer compression Delta
      d has been measured in the smectic A phase as a function of aerosil concentration
      x. Delta d(x) is shown to sensitively monitor the intermediate-rigid transition
      of the adaptive aerosil network. The dominant mechanism leading to the Delta d(x)
      profiles is the global establishment of the aerosil-induced molecular tilt in the
      smectic A phase.

PMID- 16605547
TI  - Hydrodynamics of polar liquid crystals.
AB  - Starting from a microscopic definition of an alignment vector proportional to the
      polarization, we discuss the hydrodynamics of polar liquid crystals with local C
      infinity v symmetry. The free energy for polar liquid crystals differs from that
      of nematic liquid crystals (D infinity h) in that it contains terms violating the
      n --> -n symmetry. First we show that these Z2-odd terms induce a general splay
      instability of a uniform polarized state in a range of parameters. Next we use
      the general Poisson-bracket formalism to derive the hydrodynamic equations of the
      system in the polarized state. The structure of the linear hydrodynamic modes
      confirms the existence of the splay instability.

PMID- 16605548
TI  - Surface segregation of conformationally asymmetric polymer blends.
AB  - We have generalized the Edwards' method of collective description of dense
      polymer systems in terms of effective potentials to polymer blends in the
      presence of a surface. With this method we have studied conformationally
      asymmetric athermic polymer blends in the presence of a hard wall to the first
      order in effective potentials. For polymers with the same gyration radius Rg but
      different statistical segment lengths lA and lB the excess concentration of
      stiffer polymers at the surface is derived as delta rho A(z=0) approximately (lB
      2 - lA-2)ln(R2g/l2c), where lc is a local length below of which the
      incompressibility of the polymer blend is violated. For polymer blends differing
      only in degrees of polymerization the shorter polymer enriches the wall.

PMID- 16605549
TI  - Viscoelasticity of aqueous telechelic poly(ethylene oxide) solutions: relaxation
      and structure.
AB  - We present a rheology study of associating polymers. The associating polymers are
      telechelic, composed of a water-soluble backbone (polyethylene oxide) terminated
      by hydrophobic moieties (C16H33). In aqueous solutions, these polymers self
      assemble to form micellar structures. Above a critical concentration,
      approximately 1 wt % of polymer, bridging between the micelles forms a transient
      network. Traditionally, the viscoelastic response of these polymeric solutions
      has been described using the Maxwell model. In this work we measure the
      viscoelastic properties over an extended frequency range (0.01-6000 Hz) using
      microrheology, and show that at high frequencies the rheology behaves as the
      square root of the oscillation frequency. To fit the data, we use a combination
      of the Maxwell model and the Rouse model. The Maxwell model accounts for the
      hydrophobic associations between the polymeric micelles, and the Rouse model
      accounts for the microscopic dynamics of the individual micelles.

PMID- 16605550
TI  - Free volume of an epoxy resin and its relation to structural relaxation: evidence
      from positron lifetime and pressure-volume-temperature experiments.
AB  - The microstructure of the free volume and its temperature dependence in the epoxy
      resin diglycidyl ether of bisphenol-A (DGEBA) have been examined using positron
      annihilation lifetime spectroscopy (PALS, 80-350K, 10(-5) Pa) and pressure-volume
      temperature (PVT, 293-470 K, 0.1-200MPa) experiments. Employing the Simha
      Somcynsky lattice-hole theory (S-S eos), the excess (hole) free volume fraction h
      and the specific free and occupied volumes, Vf=hV and Vocc=(1-h)V, were
      estimated. From the PALS spectra analyzed with the new routine LT9.0 the hole
      size distribution, its mean, <Vh>, and mean dispersion, sigma h, were calculated.
      <Vh> varies from 35 130 A3. From a comparison of <Vh>with V and Vf, the specific
      hole number N'h was estimated to be independent of the temperature [Nh(300
      K)=N'h/V=0.65 nm-3]. From comparison with reported dielectric and viscosity
      measurements, we found that the structural relaxation slows down faster than the
      shrinkage of the hole free volume Vf would predict on the basis of the free
      volume theory. Our results indicate that the structural relaxation in DGEBA
      operates via the free-volume mechanism only when liquidlike clusters of cells of
      the S-S lattice appear which contain a local free volume of approximately 1.5 or
      more empty S-S cells. The same conclusion follows from the pressure dependency of
      the structural relaxation and Vf. It is shown that PALS mirrors thermal volume
      fluctuations on a subnanometer scale via the dispersion in the ortho-positronium
      lifetimes. Using a fluctuation approach, the temperature dependency of the
      characteristic length of dynamic heterogeneity, xi, is estimated to vary from
      xi=1.9 nm at Tg to 1.0 nm at T/Tg>1.2. A model was proposed which relates the
      spatial structure of the free volume as concluded from PALS to the known mobility
      pattern of the dynamic glass transition at low (cooperative alpha-relaxation) and
      high (alpha-relaxation) temperatures. We discuss possible reasons for the
      differences between the results of our method and the conclusion from dynamic
      heat capacity.

PMID- 16605551
TI  - Random isotropic structures and possible glass transitions in diblock copolymer
      melts.
AB  - We study the microstructural glass transition in diblock-copolymer melts using a
      thermodynamic replica approach. Our approach performs an expansion in terms of
      the natural smallness parameter--the inverse of the scaled degree of
      polymerization N--which allows us to systematically study the approach to mean
      field behavior as the degree of polymerization increases. We find that in the
      limit of infinite chain length, both the onset of glassiness and the
      vitrification transition (Kauzmann temperature) collapse to the mean-field
      spinodal, suggesting that the spinodal can be regarded as the mean-field
      signature for glass transitions in this class of microphase-separating system. We
      also study the order-disorder transition (ODT) within the same theoretical
      framework; in particular, we include the leading-order fluctuation corrections
      due to the cubic interaction in the coarse-grained Hamiltonian, which has been
      ignored in previous studies of the ODT in block copolymers. We find that the
      cubic term stabilizes both the ordered (body-centered-cubic) phase and the glassy
      state relative to the disordered phase. In melts of symmetric copolymers the
      glass transition always occurs after the order-disorder transition (below the ODT
      temperature), but for asymmetric copolymers, it is possible for the glass
      transition to precede the ordering transition.

PMID- 16605552
TI  - Microrheological characterization of anisotropic materials.
AB  - We describe the measurement of anisotropic viscoelastic moduli in complex soft
      materials, such as biopolymer gels, via video particle tracking microrheology of
      colloid tracer particles. The use of a correlation tensor to find the axes of
      maximum anisotropy without prior knowledge, and hence the mechanical director, is
      described. The moduli of an aligned DNA gel are reported, as an application of
      the technique; this may have implications for high DNA concentrations in vivo. We
      also discuss the errors in microrheological measurement, and describe the use of
      frequency space filtering to improve displacement resolution, and hence probe
      these typically high modulus materials.

PMID- 16605553
TI  - Topology of pseudoknotted homopolymers.
AB  - We consider the folding of a self-avoiding homopolymer on a lattice, with
      saturating hydrogen bond interactions. Our goal is to numerically evaluate the
      statistical distribution of the topological genus of pseudoknotted
      configurations. The genus has been recently proposed for classifying pseudoknots
      (and their topological complexity) in the context of RNA folding. We compare our
      results on the distribution of the genus of pseudoknots, with the theoretical
      predictions of an existing combinatorial model for an infinitely flexible and
      stretchable homopolymer. We thus obtain that steric and geometric constraints
      considerably limit the topological complexity of pseudoknotted configurations, as
      it occurs for instance in real RNA molecules. We also analyze the scaling
      properties at large homopolymer length, and the genus distributions above and
      below the critical temperature between the swollen phase and the compact-globule
      phase, both in two and three dimensions.

PMID- 16605554
TI  - Dynamic functional tuning of nonlinear cortical networks.
AB  - The mammalian neocortex is a highly complex and nonlinear dynamic system. One of
      its most prominent features is an omnipresent spontaneous neuronal activity. Here
      the possible functional role of this global background for cognitive flexibility
      is studied in a prototypic mean-field model area. It is demonstrated that the
      level of global background current efficiently controls the stimulus-response
      threshold and the stability and properties of short-term memory states. Moreover,
      it can dynamically gate arbitrary cortical subnetworks, when applied to parts of
      the area as a weak bias signal. These results suggest a central functional role
      of the level of background activation: the dynamic functional tuning of
      neocortical circuits.

PMID- 16605555
TI  - Structure of DNA-CTAB-hexanol complexes.
AB  - We have probed structures of the complexes formed by DNA with the cationic
      surfactant cetyltrimethylammonium bromide in the presence of the cosurfactant
      hexanol, using small angle x-ray diffraction techniques. They are found to
      exhibit a hexagonal-->lamellar-->hexagonal transition with increasing hexanol
      content. Quantitative analysis of the diffraction data shows that the complexes
      formed at low hexanol concentrations have an intercalated hexagonal (HI)
      structure, whereas those formed at higher hexanol content have an inverted
      hexagonal (HII) structure.

PMID- 16605556
TI  - Health status and resonance in a model for living organisms under periodic stress
      and healing.
AB  - We apply the dynamic model for failures to a living organism under periodic
      stress and study how the health status of the organism evolves. It is found that
      without healing, the average fraction of intact cells decays either stepwise to
      zero or to a constant value far from zero, depending on the peak value of the
      periodic stress. As the parameter measuring the healing probability is raised
      from zero, the fraction exhibits oscillating behavior, reminiscent of periodic
      synchronization. The power spectrum at the stress frequency at first increases
      with the healing parameter, then decreases, which may be called healing
      resonance. We also study the time evolution of the system in the case that the
      healing parameter varies periodically with time and observe a transition from the
      unhealthy state to the healthy one as the healing frequency increases. This
      suggests how to adjust the frequency of medical treatment to the optimum.

PMID- 16605557
TI  - Generalized theory of semiflexible polymers.
AB  - DNA bending on length scales shorter than a persistence length plays an integral
      role in the translation of genetic information from DNA to cellular function.
      Quantitative experimental studies of these biological systems have led to a
      renewed interest in the polymer mechanics relevant for describing the
      conformational free energy of DNA bending induced by protein-DNA complexes.
      Recent experimental results from DNA cyclization studies have cast doubt on the
      applicability of the canonical semiflexible polymer theory, the wormlike chain
      (WLC) model, to DNA bending on biologically relevant length scales. This paper
      develops a theory of the chain statistics of a class of generalized semiflexible
      polymer models. Our focus is on the theoretical development of these models and
      the calculation of experimental observables. To illustrate our methods, we focus
      on a specific, illustrative model of DNA bending. We show that the WLC model
      generically describes the long-length-scale chain statistics of semiflexible
      polymers, as predicted by renormalization group arguments. In particular, we show
      that either the WLC or our present model adequately describes force-extension,
      solution scattering, and long-contour-length cyclization experiments, regardless
      of the details of DNA bend elasticity. In contrast, experiments sensitive to
      short-length-scale chain behavior can in principle reveal dramatic departures
      from the linear elastic behavior assumed in the WLC model. We demonstrate this
      explicitly by showing that our toy model can reproduce the anomalously large
      short-contour-length cyclization factors recently measured by Cloutier and Widom.
      Finally, we discuss the applicability of these models to DNA chain statistics in
      the context of future experiments.

PMID- 16605558
TI  - Instability of synchronized motion in nonlocally coupled neural oscillators.
AB  - We study nonlocally coupled Hodgkin-Huxley equations with excitatory and
      inhibitory synaptic coupling. We investigate the linear stability of the
      synchronized solution, and find numerically various nonuniform oscillatory states
      such as chimera states, wavy states, clustering states, and spatiotemporal chaos
      as a result of the instability.

PMID- 16605559
TI  - Role of inhibitory feedback for information processing in thalamocortical
      circuits.
AB  - The information transfer in the thalamus is blocked dynamically during sleep, in
      conjunction with the occurrence of spindle waves. In order to describe the
      dynamic mechanisms which control the sensory transfer of information, it is
      necessary to have a qualitative model for the response properties of thalamic
      neurons. As the theoretical understanding of the mechanism remains incomplete, we
      analyze two modeling approaches for a recent experiment by Le Masson et al.
      [Nature (London) 417, 854 (2002)] on the thalamocortical loop. We use a
      conductance based model in order to motivate an extension of the Hindmarsh-Rose
      model, which mimics experimental observations of Le Masson et al. Typically,
      thalamic neurons possess two different firing modes, depending on their membrane
      potential. At depolarized potentials, the cells fire in a single spike mode and
      relay synaptic inputs in a one-to-one manner to the cortex. If the cell gets
      hyperpolarized, T-type calcium currents generate burst-mode firing which leads to
      a decrease in the spike transfer. In thalamocortical circuits, the cell membrane
      gets hyperpolarized by recurrent inhibitory feedback loops. In the case of
      reciprocally coupled excitatory and inhibitory neurons, inhibitory feedback leads
      to metastable self-sustained oscillations, which mask the incoming input, and
      thereby reduce the information transfer significantly.

PMID- 16605560
TI  - Connectivity and expression in protein networks: proteins in a complex are
      uniformly expressed.
AB  - We explore the interplay between the protein-protein interactions network and the
      expression of the interacting proteins. It is shown that interacting proteins are
      expressed in significantly more similar cellular concentrations. This is largely
      due to interacting pairs which are part of protein complexes. We solve a generic
      model of complex formation and show explicitly that complexes form most
      efficiently when their members have roughly the same concentrations. Therefore,
      the observed similarity in interacting protein concentrations could be attributed
      to optimization for efficiency of complex formation.

PMID- 16605561
TI  - Correlated transition between two activity states of neurons.
AB  - In order to understand the dynamical properties of a neural network, it is
      important to characterize the relation between spike trains of two neurons in the
      network. In this study, we show that in some neuron pairs in inferior temporal
      cortices of macaque monkeys, spike trains of a pair are described by a two
      dimensional Poisson process whose means are modulated by a common two-state
      Markov process. The common two-state Markov process describes a correlated state
      transition between firing and nonfiring states of the constituent neurons of the
      pair.

PMID- 16605562
TI  - Condensation of DNA-actin polyelectrolyte mixtures driven by ions of different
      valences.
AB  - Multivalent ions can induce condensation of like-charged polyelectrolytes into
      compact states, a process that requires different ion valences for different
      polyelectrolyte species. In this work we examine the condensation behavior in
      binary anionic polyelectrolyte mixtures consisting of DNA coils and F-actin rods
      in the presence of monovalent, divalent, and trivalent ions. As expected,
      monovalent ions do not condense either component and divalent ions selectively
      condense F-actin rods out of the polyelectrolyte mixture. For trivalent ions,
      however, we observe a microphase separation between the two polyelectrolytes into
      coexisting finite-sized F-actin bundles and DNA toroids. Further, by increasing
      the DNA volume fraction in the mixture, condensed F-actin bundles can be
      completely destabilized, leading to only DNA condensation within the mixture. We
      examine a number of possible causes and propose a model based on polyelectrolyte
      competition for ions.

PMID- 16605563
TI  - Network growth models and genetic regulatory networks.
AB  - We study a class of growth algorithms for directed graphs that are candidate
      models for the evolution of genetic regulatory networks. The algorithms involve
      partial duplication of nodes and their links, together with the innovation of new
      links, allowing for the possibility that input and output links from a newly
      created node may have different probabilities of survival. We find some
      counterintuitive trends as the parameters are varied, including the broadening of
      the in-degree distribution when the probability for retaining input links is
      decreased. We also find that both the scaling of transcription factors with
      genome size and the measured degree distributions for genes in yeast can be
      reproduced by the growth algorithm if and only if a special seed is used to
      initiate the process.

PMID- 16605564
TI  - Periodic and aperiodic traveling pulses in population dynamics: an example from
      the occurrence of epidemic infections.
AB  - The dynamics of the occurrence of the dengue hemorrhagic fever in the 72
      provinces of Thailand is investigated by performing a proper orthogonal
      decomposition (POD) on spatiotemporal data. Using this technique, we are able to
      identify and select the contribution of different modes, selected according to
      the energy content, to the evolution of the epidemic during 14 years. We found
      that the phenomenon is characterized by periodic cycles of yearly occurrence
      characterized by spatial scales of about 420 km. Superimposed on this basic mode,
      POD analysis is able to reveal the presence of high-energetic aperiodic traveling
      pulses of the epidemic, which extend spatially for about 510 km from Bangkok.

PMID- 16605565
TI  - Noise-driven switching between limit cycles and adaptability in a small
      dimensional excitable network with balanced coupling.
AB  - We study a system of globally coupled FitzHugh-Nagumo equations. Each unit is
      either excitatory or inhibitory. If the numbers of units of both types are in a
      specific ratio, we observe the presence of multistable oscillatory states with
      different excitation or firing rates. In the presence of noise, there is noise
      driven switching between these states and the resultant firing pattern is long
      range correlated. The choice between higher and lower frequency oscillations
      depends on the input, which results in increasing adaptability of the system's
      output to the periodic input.

PMID- 16605567
TI  - Full q-space analysis of x-ray scattering of multilamellar membranes at liquid
      solid interfaces.
AB  - A method for analyzing the x-ray scattering of a stack of phospholipid membranes
      at the solid-liquid interface in excess water is presented. It is argued that
      bilayers near the substrate fluctuate less significantly than the ones away from
      it and, therefore, make a larger contribution to the specular reflection at the
      low index Bragg peaks. But the diffuse scattering due to thermal fluctuations
      corrupts the Bragg peaks at high angles so that the specular contribution is not
      clearly observable. In the midst the specular reflection and the diffuse
      scattering cannot be separated easily and must be analyzed simultaneously. The
      height-difference correlation function derived from a modified Caille theory
      enables one to simulate the longitudinal and the transverse scans in the same
      theoretical framework to yield more reliable structural parameters. The
      theoretical apparatus is successfully applied to the experimental data on DOPC
      membranes.

PMID- 16605566
TI  - Cross-correlation of instantaneous phase increments in pressure-flow
      fluctuations: applications to cerebral autoregulation.
AB  - We investigate the relationship between the blood flow velocities (BFV) in the
      middle cerebral arteries and beat-to-beat blood pressure (BP) recorded from a
      finger in healthy and post-stroke subjects during the quasisteady state after
      perturbation for four different physiologic conditions: supine rest, head-up
      tilt, hyperventilation, and CO2 rebreathing in upright position. To evaluate
      whether instantaneous BP changes in the steady state are coupled with
      instantaneous changes in the BFV, we compare dynamical patterns in the
      instantaneous phases of these signals, obtained from the Hilbert transform, as a
      function of time. We find that in post-stroke subjects the instantaneous phase
      increments of BP and BFV exhibit well-pronounced patterns that remain stable in
      time for all four physiologic conditions, while in healthy subjects these
      patterns are different, less pronounced, and more variable. We propose an
      approach based on the cross-correlation of the instantaneous phase increments to
      quantify the coupling between BP and BFV signals. We find that the maximum
      correlation strength is different for the two groups and for the different
      conditions. For healthy subjects the amplitude of the cross-correlation between
      the instantaneous phase increments of BP and BFV is small and attenuates within 3
      5 heartbeats. In contrast, for post-stroke subjects, this amplitude is
      significantly larger and cross-correlations persist up to 20 heartbeats. Further,
      we show that the instantaneous phase increments of BP and BFV are cross
      correlated even within a single heartbeat cycle. We compare the results of our
      approach with three complementary methods: direct BP-BFV cross-correlation,
      transfer function analysis, and phase synchronization analysis. Our findings
      provide insight into the mechanism of cerebral vascular control in healthy
      subjects, suggesting that this control mechanism may involve rapid adjustments
      (within a heartbeat) of the cerebral vessels, so that BFV remains steady in
      response to changes in peripheral BP.

PMID- 16605568
TI  - Pattern formation in a gene network model with boundary shape dependence.
AB  - A fundamental task in developmental biology is to identify the mechanisms which
      drive morphogenesis. Traditionally pattern formation have been modeled mainly
      using Turing-type mechanisms, where complex patterns arise by symmetry breaking.
      However, there is a growing experimental evidence that the influence of signals
      derived from surrounding tissues can contribute to the patterning processes. In
      this paper, we show that the interplay between the shape of surrounding tissues
      and a hierarchically organized gene regulatory network can be able to induce
      stable complex patterns. The rise of these patterns depends strongly on the shape
      of the surrounding tissues.

PMID- 16605569
TI  - Budded membrane microdomains as tension regulators.
AB  - We propose a mechanism by which changes of the mechanical tension of a composite
      lipid membrane are buffered by the invagination of membrane domains. We show that
      domain invagination, driven by differences in chemical composition, is a first
      order transition controlled by membrane tension. The invaginated domains play the
      role of a membrane reservoir, exchanging area with the main membrane, and impose
      an equilibrium tension entirely controlled by their mechanical properties. The
      dynamical response of the reservoir reflects the tension-dependent kinetics of
      the domain shape transition, so that the tension of such a composite membrane is
      inherently transient and dynamical. The implications of this phenomenon for the
      mechanical properties of the membranes of living cells, where invaginated
      membrane domains are known to exist, are discussed.

PMID- 16605570
TI  - Modeling DNA loops using the theory of elasticity.
AB  - An elastic rod model of a protein-bound DNA loop is adapted for application in
      multi-scale simulations of protein-DNA complexes. The classical Kirchhoff system
      of equations which describes the equilibrium structure of the elastic loop is
      modified to account for the intrinsic twist and curvature, anisotropic bending
      properties, and electrostatic charge of DNA. The effects of bending anisotropy
      and electrostatics are studied for the DNA loop clamped by the lac repressor
      protein. For two possible lengths of the loop, several topologically different
      conformations are predicted and extensively analyzed over the broad range of
      model parameters describing DNA bending and electrostatic properties. The scope
      and applications of the model in already accomplished and in future multi-scale
      studies of protein-DNA complexes are discussed.

PMID- 16605571
TI  - Clustering of protein structures using hydrophobic free energy and solvent
      accessibility of proteins.
AB  - The hydrophobic free energy and solvent accessibility of amino acids are used to
      study the relationship between the primary structure and structural
      classification of large proteins. A measure representation and a Z curve
      representation of protein sequences are proposed. Fractal analysis of the measure
      and Z curve representations of proteins and multifractal analysis of their
      hydrophobic free energy and solvent accessibility sequences indicate that the
      protein sequences possess correlations and multifractal scaling. The parameters
      from the fractal and multifractal analyses on these sequences are used to
      construct some parameter spaces. Each protein is represented by a point in these
      spaces. A method is proposed to distinguish and cluster proteins from the alpha,
      beta, alpha + beta, and alpha/beta structural classes in these parameter spaces.
      Fisher's linear discriminant algorithm is used to give a quantitative assessment
      of our clustering on the selected proteins. Numerical results indicate that the
      discriminant accuracies are satisfactory. In particular, they reach 94.12% and
      88.89% in separating proteins from {alpha, alpha + beta, alpha/beta} proteins in
      a three-dimensional space.

PMID- 16605572
TI  - Geometry of proteins: hydrogen bonding, sterics, and marginally compact tubes.
AB  - The functionality of proteins is governed by their structure in the native state.
      Protein structures are made up of emergent building blocks of helices and almost
      planar sheets. A simple coarse-grained geometrical model of a flexible tube
      barely subject to compaction provides a unified framework for understanding the
      common character of globular proteins. We argue that a recent critique of the
      tube idea is not well founded.

PMID- 16605573
TI  - Dynamic transitions in coupled motor proteins.
AB  - The effect of interactions on dynamics of coupled motor proteins is investigated
      theoretically. A simple stochastic discrete model, which allows one to calculate
      explicitly the dynamic properties, is developed. It is shown that there are two
      dynamic regimes, depending on the interaction between the particles. For strong
      interactions the motor proteins move as one tight cluster, while for weak
      interactions there is no correlation in the motion of the proteins, and the
      particle separation increases steadily with time. The boundary between the two
      regimes is specified by a critical interaction that has a nonzero value only for
      the coupling of the asymmetric motor proteins, and it depends on the temperature
      and transition rates. At the critical interaction there is a change in slope for
      the mean velocities and a discontinuity in the dispersions of the motor proteins
      as a function of interactions.

PMID- 16605574
TI  - Opening of a weak link in a semiflexible ring polymer.
AB  - The dynamics of contact formation between different parts of a long chain
      molecule is of considerable interest in biology. The related processes of opening
      of a loop or closing to form a loop also are of considerable interest and have
      attracted the attention of experimentalists/theorists. For closing, results are
      available in the completely flexible limit. However, this limit is not realized
      in many cases. Recently, there have been investigations for the semiflexible case
      too. We develop an approach, which leads to an easy description of the dynamics,
      incorporating semiflexibility rigorously into account. With this approach, the
      dynamics of a semiflexible polymer ring formed by a weak bond between the two
      ends can be modeled as the escape of a particle over a barrier in a
      multidimensional potential energy surface. We then calculate the rate of opening
      using a multidimensional transition state theory. Effects of friction on the rate
      are also taken into account using the standard coupling to a bath of harmonic
      oscillators. We find that for shorter chains (i.e., semiflexible), the rate of
      opening is strongly length dependent and is well described by the equation
      A(L/lp)v exp(Blp/L), with L as the length, and lp as the persistence length, A, B
      as the constants, and v approximately 1.2.

PMID- 16605575
TI  - Application of random matrix theory to microarray data for discovering functional
      gene modules.
AB  - We show that spectral fluctuation of coexpression correlation matrices of yeast
      gene microarray profiles follows the description of the Gaussian orthogonal
      ensemble (GOE) of the random matrix theory (RMT) and removal of small values of
      the correlation coefficients results in a transition from the GOE statistics to
      the Poisson statistics of the RMT. This transition is directly related to the
      structural change of the gene expression network from a global network to a
      network of isolated modules.

PMID- 16605577
TI  - Non-Markovian Fokker-Planck equation: solutions and first passage time
      distribution.
AB  - We investigate the solutions and first passage time distribution for an anomalous
      diffusion process governed by a generalized non-Markovian Fokker-Planck equation.
      In our analysis, we also consider the presence of external forces and absorbent
      (source) terms. In addition, we show that a rich class of diffusive processes,
      including normal and anomalous ones, can be obtained from the solutions found
      here.

PMID- 16605576
TI  - Single molecule study of DNA conductivity in aqueous environment.
AB  - The dc electrical conductivity of double stranded DNA is investigated
      experimentally. Single DNA molecules are manipulated with subpiconewton force and
      deposited on gold nanoelectrodes by optical traps. The DNA is modified at its
      ends for specific bead attachments and along the chain to favor charge transfer
      between the DNA base pair stack and the electrodes. For an electrode separation
      of 70 nm we find, in aqueous environment, electrical resistances above 100 G
      Omega indicating that even for weak stretching the double helix is almost
      insulating at this length scale.

PMID- 16605578
TI  - Molecular dynamics simulations of ballistic annihilation.
AB  - Using event-driven molecular dynamics we study one- and two-dimensional ballistic
      annihilation. We estimate exponents xi and gamma, which describe the long-time
      decay of the number of particles [n(t) approximately t-xi] and of their typical
      velocity [v(t) approximately t-gamma]. To a good accuracy our results confirm the
      scaling relation xi+gamma=1. In the two-dimensional case our results are in good
      agreement with those obtained from Boltzmann kinetic theory.

PMID- 16605579
TI  - Structural corrections to Stokes-Einstein relation for liquid metals near
      freezing.
AB  - Using recent progress relating the self-diffusion coefficient to excess entropy,
      structural corrections to the Stokes-Einstein relation are proposed for liquid
      metals near the melting temperature.

PMID- 16605580
TI  - de Gennes slowing in a liquid metal revisited: a neutron spin-echo study.
AB  - In liquids the decay of density fluctuations shows a slowing down at the
      structure factor maximum, which is well known as de Gennes narrowing. Molecular
      dynamics simulations of the liquid metal rubidium and mode coupling theory
      suggested that this process can be described by a two-step relaxation function.
      We have probed these predictions with inelastic neutron scattering using the spin
      echo technique to measure the dynamics directly in the time domain. The dynamics
      of liquid rubidium was investigated near the melting point at times beyond the
      fast contribution. The resulting intermediate-scattering function is in
      remarkable agreement with predicted values from the mode coupling calculations.

PMID- 16605581
TI  - Dynamics of capillary condensation in aerogels.
AB  - Dynamics of capillary condensation of liquid 4He in various density silica
      aerogels was investigated systematically. Interfaces were clearly visible when
      bulk liquid was rapidly sucked into the aerogel. Time evolution of the interface
      positions was consistent with the Washburn model and their effective pore radii
      were obtained. Condensation was a single step in a dense aerogel and two steps in
      a low density aerogel. Crossover between the two types of condensation was
      observed in an intermediate density aerogel. Variety of the dynamics may be the
      manifestation of the fractal nature of aerogels which had a wide range of
      distribution of pore radii.

PMID- 16605582
TI  - Phase transitions of semiflexible hard-sphere chain liquids.
AB  - We present a density-functional theory for describing liquid-crystalline phase
      transitions in a fluid of semiflexible hard-sphere chain molecules based on the
      Onsager second-virial approximation for the free energy. Key ingredients of this
      theory are the generation of semiflexible chain conformations and calculation of
      the pair excluded volume and excluded area using a single-chain Monte Carlo
      enumeration method. First, we investigate the isotropic-nematic phase transition.
      Next, the theory is extended to account for a smectic-A phase by a bifurcation
      analysis around the nematic solution. The perturbation is calculated using a
      lowest-order Fourier series representation.

PMID- 16605583
TI  - Width of percolation transition in complex networks.
AB  - It is known that the critical probability for the percolation transition is not a
      sharp threshold. Actually it is a region of nonzero width Deltap(c) for systems
      of finite size. Here we present evidence that for complex networks Deltap(c)
      approximately p(c)/l, where l approximately Nnu(opt), where is the average length
      of the percolation cluster, and N is the number of nodes in the network. For
      Erdos-Renyi graphs nu(opt)=1/3, while for scale-free networks with a degree
      distribution P(k) approximately k(-lambda) and 3<lambda<4, nu(opt)=(lambda
      3)/(lambda-1) . We show analytically and numerically that the survivability
      S(p,l), which is the probability of a cluster to survive l chemical shells at
      probability p, behaves near criticality as S(p,l)=S(p(c),l)exp[(p-p(c))l/p(c)].
      Thus for probabilities inside the region |p-p(c)|<p(c)/l the behavior of the
      system is indistinguishable from that of the critical point.

PMID- 16605584
TI  - Fluctuation theorem applied to the Nose-Hoover thermostated Lorentz gas.
AB  - We present numerical evidence supporting the validity of the Gallavotti-Cohen
      fluctuation theorem applied to the driven Lorentz gas with Nose-Hoover
      thermostating. It is moreover argued that the asymptotic form of the fluctuation
      formula is independent of the amplitude of the driving force in the limit where
      it is small.

PMID- 16605585
TI  - Information propagation on modular networks.
AB  - Networks with a community (or modular) structure underlie many social and
      biological phenomena. In such a network individuals tend to form sparsely linked
      local communities, each having dense internal connections. We investigate the
      dynamics of information propagation on modular networks by using a three-state
      epidemic model with a unit spreading rate (i.e., the probability for a
      susceptible individual to be "infected" with the information is one). We find a
      surprising, resonancelike phenomenon: the information lifetime on the network can
      be maximized by the number of modules. The result can be useful for optimizing or
      controlling information spread on social or biological networks.

PMID- 16605586
TI  - Crossovers in scale-free networks on geographical space.
AB  - Complex networks are characterized by several topological properties: degree
      distribution, clustering coefficient, average shortest path length, etc. Using a
      simple model to generate scale-free networks embedded on geographical space, we
      analyze the relationship between topological properties of the network and
      attributes (fitness and location) of the vertices in the network. We find there
      are two crossovers for varying the scaling exponent of the fitness distribution.

PMID- 16605587
TI  - Field-induced Berezinskii-Kosterlitz-Thouless transition and string-density
      plateau in the anisotropic triangular antiferromagnetic Ising model.
AB  - The field-induced Berezinskii-Kosterlitz-Thouless (BKT) transition in the ground
      state of the triangular antiferromagnetic Ising model is studied by the level
      spectroscopy method. We analyze dimensions of operators around the BKT line, and
      estimate the BKT point H(c) approximately equal to 0.5229 +/-0.001, which is
      followed by the level-consistency check to demonstrate the accuracy of our
      estimate. Further we investigate the anisotropic case to clarify the stability of
      the field-induced string-density plateau against an incommensurate liquid state
      by the density-matrix renormalization-group method.

PMID- 16605588
TI  - Second-order variation in elastic fields of a tensile planar crack with a curved
      front.
AB  - We derive the second-order variation in the local static stress intensity factor
      of a tensile crack with a curved front. We then discuss the relevance of this
      result to the stability analysis of such fronts, and propose an equation of
      motion of planar crack fronts in heterogeneous media that contains two main
      ingredients--irreversibility of the propagation of the crack front and nonlinear
      effects.

PMID- 16605589
TI  - Spectral statistics in an open parametric billiard system.
AB  - We present experimental results on the eigenfrequency statistics of a
      superconducting, chaotic microwave billiard containing a rotatable obstacle.
      Deviations of the spectral fluctuations from predictions based on Gaussian
      orthogonal ensembles of random matrices are found. They are explained by treating
      the billiard as an open scattering system in which microwave power is coupled in
      and out via antennas. To study the interaction of the quantum (or wave) system
      with its environment, a highly sensitive parametric correlator is used.

PMID- 16605590
TI  - Exponentially growing solutions in homogeneous Rayleigh-Benard convection.
AB  - It is shown that homogeneous Rayleigh-Benard flow, i.e., Rayleigh-Benard
      turbulence with periodic boundary conditions in all directions and a volume
      forcing of the temperature field by a mean gradient, has a family of exact,
      exponentially growing, separable solutions of the full nonlinear system of
      equations. These solutions are clearly manifest in numerical simulations above a
      computable critical value of the Rayleigh number. In our numerical simulations
      they are subject to secondary numerical noise and resolution dependent
      instabilities that limit their growth to produce statistically steady turbulent
      transport.

PMID- 16605591
TI  - Omnidirectional total reflection for liquid surface waves propagating over a
      bottom with one-dimensional periodic undulations.
AB  - We study theoretically the propagation of liquid surface waves over a bottom with
      one-dimensional (1D) periodic undulations. We find a general criterion for
      omnidirectional total reflection in such a system. Numerical simulations based on
      a transfer matrix method demonstrate unambiguously the existence of
      omnidirectional total reflection for liquid surface waves propagating over a
      bottom with 1D periodic undulations.

PMID- 16605592
TI  - Formation of density waves in traffic flow through intersecting roads.
AB  - The formation of density waves in two intersecting roads, with a traffic circle
      at the intersection, is studied. It is found that, depending on the traffic
      densities in the two roads, density waves can form in the traffic circle and in
      one or both of the roads. Depending on the expression chosen for the optimal
      velocity, either the congestion moves entirely to the traffic circle or the
      congestion becomes confined to the traffic circle and a part of the road
      approaching the traffic circle.

PMID- 16605593
TI  - Geographical effects on cascading breakdowns of scale-free networks.
AB  - Cascading breakdowns of real networks have resulted in severe accidents in recent
      years. In this paper, we study the effects of geographical structure on the
      cascading phenomena of load-carrying scale-free networks. Our essential finding
      is that when networks are more geographically constrained, i.e., more locally
      interconnected, they tend to have larger cascading breakdowns. Explanations are
      provided in terms of the effects of cycles and the distributions of betweenness
      over degrees.

PMID- 16605594
TI  - Stochastic energetics of quantum transport.
AB  - We examine the stochastic energetics of directed quantum transport due to
      rectification of nonequilibrium thermal fluctuations. We calculate the quantum
      efficiency of a ratchet device both in presence and absence of an external load
      to characterize two quantifiers of efficiency. It has been shown that the quantum
      current as well as efficiency in absence of load (Stokes efficiency) is higher as
      compared to classical current and efficiency, respectively, at low temperature.
      The conventional efficiency of the device in presence of load on the other hand
      is higher for a classical system in contrast to its classical counterpart. The
      maximum conventional efficiency being independent of the nature of the bath and
      the potential remains the same for classical and quantum systems.

PMID- 16605595
TI  - Automatic filters for the detection of coherent structure in spatiotemporal
      systems.
AB  - Most current methods for identifying coherent structures in spatially extended
      systems rely on prior information about the form which those structures take.
      Here we present two approaches to automatically filter the changing
      configurations of spatial dynamical systems and extract coherent structures. One,
      local sensitivity filtering, is a modification of the local Lyapunov exponent
      approach suitable to cellular automata and other discrete spatial systems. The
      other, local statistical complexity filtering, calculates the amount of
      information needed for optimal prediction of the system's behavior in the
      vicinity of a given point. By examining the changing spatiotemporal distributions
      of these quantities, we can find the coherent structures in a variety of pattern
      forming cellular automata, without needing to guess or postulate the form of that
      structure. We apply both filters to elementary and cyclical cellular automata
      (ECA and CCA) and find that they readily identify particles, domains, and other
      more complicated structures. We compare the results from ECA with earlier ones
      based upon the theory of formal languages and the results from CCA with a more
      traditional approach based on an order parameter and free energy. While
      sensitivity and statistical complexity are equally adept at uncovering structure,
      they are based on different system properties (dynamical and probabilistic,
      respectively) and provide complementary information.

PMID- 16605596
TI  - Growth model for complex networks with hierarchical and modular structures.
AB  - A hierarchical and modular network model is suggested by adding a growth rule
      along with the preferential attachment (PA) rule into Motter's modeling
      procedure. The proposed model has an increasing number of vertices but a fixed
      number of modules and hierarchical levels. The vertices form lowest-level modules
      which in turn constitute higher-level modules hierarchically. The creation of
      connections between two vertices in a single module or in two different modules
      of the same level obeys the PA rule. The structural characteristics of this model
      are investigated analytically and numerically. The results show that the degree
      distribution, the module size distribution, and the clustering function of the
      model possess a power-law property which is similar to that in many real-world
      networks. The model is then used to predict the growth trends of real-world
      networks with modular and hierarchical structures. By comparing this model with
      those real-world networks, an interesting conclusion is found: that many real
      world networks are in their early stages of development, and when the growth time
      is large enough, the modules and levels of the networks will be ultimately
      merged.

PMID- 16605597
TI  - Incorporating inertia into multiagent systems.
AB  - We consider a model that demonstrates the crucial role of inertia and stickiness
      in multiagent systems, based on the minority game. The inertia of an agent is
      introduced into the game model by allowing agents to apply hypothesis testing
      when choosing their best strategies, thereby reducing their reactivity toward
      changes in the environment. We find by extensive numerical simulations that our
      game shows a remarkable improvement of global cooperation throughout the whole
      phase space. In other words, the maladaptation behavior due to over-reaction of
      agents is removed. These agents are also shown to be advantageous over the
      standard ones, which are sometimes too sensitive to attain a fair success rate.
      We also calculate analytically the minimum amount of inertia needed to achieve
      the above improvement. Our calculation is consistent with the numerical
      simulation results. Finally, we review some related works in the field that show
      similar behaviors and compare them to our work.

PMID- 16605598
TI  - Effects of network structure and routing strategy on network capacity.
AB  - The capacity of maximum end-to-end traffic flow the network is able to handle
      without overloading is an important index for network performance in real
      communication systems. In this paper, we estimate the variations of network
      capacity under different routing strategies for three different topologies.
      Simulation results reveal that the capacity depends on the underlying network
      structure and the capacity increases as the network becomes more homogeneous. It
      is also observed that the network capacity is greatly enhanced when the new
      traffic awareness routing strategy is adopted in each network structure.

PMID- 16605599
TI  - Defect-free global minima in Thomson's problem of charges on a sphere.
AB  - Given unit points charges on the surface of a unit conducting sphere, what
      configuration of charges minimizes the Coulombic energy SigmaN i>(j=1)1/r(ij)?
      Due to an exponential rise in good local minima, finding global minima for this
      problem, or even approaches to do so has proven extremely difficult. For
      N=10(h2+hk+k2)+2 recent theoretical work based on elasticity theory, and
      subsequent numerical work has shown, that for N approximately same or greater
      than 500-1000, adding dislocation defects to a symmetric icosadeltahedral lattice
      lowers the energy. Here we show that in fact this approach holds for all N, and
      we give a complete or near complete catalogue of defect free global minima.

PMID- 16605600
TI  - Crack-cluster distributions in the random fuse model.
AB  - Using large-scale numerical simulations and extensive sampling, we analyze the
      scaling properties of the crack-cluster distribution and the largest crack
      cluster distribution at the peak load. The simulations are performed using both
      two-dimensional and three-dimensional random fuse models. The numerical results
      indicate that in contrast with the randomly diluted networks (percolation
      disorder), the crack-cluster distribution in the random fuse model at the peak
      load follows neither a power law nor an exponential distribution. The largest
      crack-cluster distribution at the peak load follows a lognormal distribution, and
      this is discussed in the context of whether there exists a relationship between
      the largest crack-cluster size distribution at peak load and the fracture
      strength distribution. Contrary to popular belief, we find that the fracture
      strength and the largest crack-cluster size at the peak load are uncorrelated.
      Indeed, quite often, the final spanning crack is formed not due to the
      propagation of the largest crack at the peak load, but instead due to coalescence
      of smaller cracks.

PMID- 16605601
TI  - From simple to complex networks: inherent structures, barriers, and valleys in
      the context of spin glasses.
AB  - Given discrete degrees of freedom (spins) on a graph interacting via an energy
      function, what can be said about the energy local minima and associated inherent
      structures? Using the lid algorithm in the context of a spin glass energy
      function, we investigate the properties of the energy landscape for a variety of
      graph topologies. First, we find that the multiplicity N(s) of the inherent
      structures generically has a log-normal distribution. In addition, the large
      volume limit of ln <N(s)>/<ln N(s)> differs from unity, except for the
      Sherrington-Kirkpatrick model. Second, we find simple scaling laws for the growth
      of the height of the energy barrier between the two degenerate ground states and
      the size of the associated valleys. For finite connectivity models, changing the
      topology of the underlying graph does not modify qualitatively the energy
      landscape, but at the quantitative level the models can differ substantially.

PMID- 16605602
TI  - Exact kinetics of sol-gel transition in a coagulating mixture.
AB  - The formation of a gel in a two component disperse system wherein binary
      coagulation governs the temporal changes to particle composition spectra is
      studied under the assumption that the coagulation kernel is proportional to
      m1n2+m2n1, with m,n being the numbers of monomers of the first and the second
      component in the coalescing pair of particles. This model is shown to reveal the
      sol-gel transition, i.e., the formation of one giant cluster with the mass
      comparable to the total mass of the whole system. This paper reports on the exact
      solution of this model within the Marcus-Lushnikov stochastic scheme. The
      evolution equation for the generating functional of the probability to find in
      the system a given set of occupation numbers (the numbers of particles containing
      m and n monomers of each component) at time t is formulated and solved exactly.
      The expression for the particle composition spectrum is derived and analyzed in
      the thermodynamic limit. It is shown that after a critical time a giant single
      particle (the gel) appears. The time evolution of its composition is found.
      Special attention is given to the transition point, where the gel is appearing.
      The time dependencies of the gel composition, the number concentration, and the
      second moments of the particle composition spectrum are found.

PMID- 16605603
TI  - Flocking regimes in a simple lattice model.
AB  - We study a one-dimensional lattice flocking model incorporating all three of the
      flocking criteria proposed by Reynolds [Computer Graphics 21, 4 (1987)]:
      alignment, centering, and separation. The model generalizes that introduced by O.
      J. O'Loan and M. R. Evans [J. Phys. A. 32, L99 (1999)]. We motivate the dynamical
      rules by microscopic sampling considerations. The model exhibits various flocking
      regimes: the alternating flock, the homogeneous flock, and dipole structures. We
      investigate these regimes numerically and within a continuum mean-field theory.

PMID- 16605604
TI  - Equilibrium correlations in charged fluids coupled to the radiation field.
AB  - We provide an exact microscopic statistical treatment of particle and field
      correlations in a system of quantum charges in equilibrium with a classical
      radiation field. Using the Feynman-Kac-Ito representation of the Gibbs weight,
      the system of particles is mapped onto a collection of random charged wires. The
      field degrees of freedom can be integrated out, providing an effective pairwise
      magnetic potential. We then calculate the contribution of the transverse field
      coupling to the large-distance particle correlations. The asymptotics of the
      field correlations in the plasma are also exactly determined.

PMID- 16605605
TI  - Multifractal analysis of evolving noise associated with unstable plastic flow.
AB  - Plastic flow instability attracts increasing interest as a self-organization
      phenomenon showing various dynamical regimes, including deterministic chaos and
      self-organized criticality. The analysis of the associated nonrandom noise-
      drastic jumps of the mechanical stress--however, confronts the variation of the
      noise average parameters due to the evolution of the dislocation microstructure.
      The present paper examines some limitations of the multifractal approach to the
      study of the evolving noise. The applicability of the multifractal analysis to
      practical situations is proven using the example of discontinuous deformation
      curves observed under conditions of the Portevin-Le Chatelier effect in an A1Mg
      alloy, as well as model signals generated by stretching multifractal Cantor sets.
      It is found that the smooth trends in the stress serration parameters may narrow
      the range of the scale invariant behavior associated with the multifractal
      structure, but do not essentially mask it.

PMID- 16605606
TI  - Influence of polydispersity on the critical parameters of an effective-potential
      model for asymmetric hard-sphere mixtures.
AB  - We report a Monte Carlo simulation study of the properties of highly asymmetric
      binary hard-sphere mixtures. This system is treated within an effective fluid
      approximation in which the large particles interact through a depletion potential
      [R. Roth, Phys. Rev. E 62 5360 (2000)] designed to capture the effects of a
      virtual sea of small particles. We generalize this depletion potential to include
      the effects of explicit size dispersity in the large particles and consider the
      case in which the particle diameters are distributed according to a Schulz form
      having a degree of polydispersity 14%. The resulting alteration (with respect to
      the monodisperse limit) of the metastable fluid-fluid critical point parameters
      is determined for two values of the ratio of the diameters of the small and large
      particles: q(triple bond)sigma(s)/(-)sigma(b)=0.1 and q=0.05. We find that the
      inclusion of polydispersity moves the critical point to lower reservoir volume
      fractions of the small particles and high volume fractions of the large ones. The
      estimated critical point parameters are found to be in good agreement with those
      predicted by a generalized corresponding states argument which provides a link to
      the known critical adhesion parameter of the adhesive hard-sphere model. Finite
      size scaling estimates of the cluster percolation line in the one phase fluid
      region indicate that inclusion of polydispersity moves the critical point deeper
      into the percolating regime. This suggests that phase separation is more likely
      to be preempted by dynamical arrest in polydisperse systems.

PMID- 16605607
TI  - Nonequilibrium phase transitions and finite-size scaling in weighted scale-free
      networks.
AB  - We consider nonequilibrium phase transitions, such as epidemic spreading, in
      weighted scale-free networks, in which highly connected nodes have a relatively
      smaller ability to transfer infection. We solve the dynamical mean-field
      equations and discuss finite-size scaling theory. The theoretical predictions are
      confronted with the results of large scale Monte Carlo simulations on the
      weighted Barabasi-Albert network. Local scaling exponents are found different at
      a typical site and at a node with very large connectivity.

PMID- 16605608
TI  - Growth of order in an anisotropic Swift-Hohenberg model.
AB  - We have studied the ordering kinetics of a two-dimensional anisotropic Swift
      Hohenberg (SH) model numerically. The defect structure for this model is simpler
      than for the isotropic SH model. One finds only dislocations in the aligned
      ordering striped system. The motion of these point defects is strongly influenced
      by the anisotropic nature of the system. We developed accurate numerical methods
      for following the trajectories of dislocations. This allows us to carry out a
      detailed statistical analysis of the dynamics of the dislocations. The average
      speeds for the motion of the dislocations in the two orthogonal directions obey
      power laws in time with different amplitudes but the same exponents. The position
      and velocity distribution functions are only weakly anisotropic.

PMID- 16605609
TI  - Random walks with shrinking steps: first-passage characteristics.
AB  - We study the mean first-passage time of a one-dimensional random walker with step
      sizes decaying exponentially in discrete time. That is step sizes go like
      lambda(n) with lambda< or =1. We also present, for pedagogical purposes, a
      continuum system with a diffusion constant decaying exponentially in continuous
      time. Qualitatively both systems are alike in their global properties. However,
      the discrete case shows very rich mathematical structure, depending on the value
      of the shrinking parameter, such as self-repetitive and fractal-like structure
      for the first-passage characteristics. The results we present show that the most
      important quantitative behavior of the discrete case is that the support of the
      distribution function evolves in time in a rather complicated way in contrast to
      the time independent lattice structure of the ordinary random walker. We also
      show that there are critical values of lambda defined by the equation lambda(K) +
      2lambda(P)-2=0 with {K,N}[formula: see text] where the mean first-passage time
      undergoes transitions.

PMID- 16605610
TI  - Coherence and correlations in multitime quantum measurements of stochastic
      quantum trajectories.
AB  - Quantum effects on multitime distributions and correlation functions of single
      objects, stemming from both the dynamics and repeated measurements, are
      calculated for a driven harmonic system using a superoperator generating
      functional formalism. Marked differences between multipoint observables
      associated with classical and quantum measurements are identified. The effects of
      quantum collapse and measurement resolution are discussed.

PMID- 16605611
TI  - Anomalous diffusion for overdamped particles driven by cross-correlated white
      noise sources.
AB  - We study the statistical properties of overdamped particles driven by two cross
      correlated multiplicative Gaussian white noises in a time-dependent environment.
      Using the Langevin and Fokker-Planck approaches, we derive the exact probability
      distribution function for the particle positions, calculate its moments, and find
      their corresponding long-time, asymptotic behaviors. The generally anomalous
      diffusive regimes of the particles are classified, and their dependence on the
      friction coefficient and the characteristics of the noises is analyzed in detail.
      The asymptotic predictions are confirmed by exact solutions for two examples.

PMID- 16605612
TI  - Genetic attack on neural cryptography.
AB  - Different scaling properties for the complexity of bidirectional synchronization
      and unidirectional learning are essential for the security of neural
      cryptography. Incrementing the synaptic depth of the networks increases the
      synchronization time only polynomially, but the success of the geometric attack
      is reduced exponentially and it clearly fails in the limit of infinite synaptic
      depth. This method is improved by adding a genetic algorithm, which selects the
      fittest neural networks. The probability of a successful genetic attack is
      calculated for different model parameters using numerical simulations. The
      results show that scaling laws observed in the case of other attacks hold for the
      improved algorithm, too. The number of networks needed for an effective attack
      grows exponentially with increasing synaptic depth. In addition, finite-size
      effects caused by Hebbian and anti-Hebbian learning are analyzed. These learning
      rules converge to the random walk rule if the synaptic depth is small compared to
      the square root of the system size.

PMID- 16605613
TI  - Quantum-classical transition of photon-Carnot engine induced by quantum
      decoherence.
AB  - We study the physical implementation of the photon-Carnot engine (PCE) based on
      the cavity quantum electrodynamics system [M. O. Scully, M. Suhail Zubairy, G. S.
      Agarwal, and H. Walther, Science 299, 862 (2003)]. Here we analyze two
      decoherence mechanisms for the more practical systems of PCE, the dissipation of
      photon field, and the pure dephasing of the input atoms. As a result we find that
      (i) the PCE can work well to some extent even in the existence of the cavity loss
      (photon dissipation) and (ii) the short-time atomic dephasing, which can destroy
      the PCE, is a fatal problem to be overcome.

PMID- 16605614
TI  - Structure of peer-to-peer social networks.
AB  - This paper presents a statistical analysis of the structure of peer-to-peer (P2P)
      social networks that captures social associations of distributed peers in
      resource sharing. Peer social networks appear to be mainly composed of pure
      resource providers that guarantee high resource availability and reliability of
      P2P systems. The major peers that both provide and request resources are only a
      small fraction. The connectivity between peers, including undirected, directed
      (out and in) and weighted connections, is scale-free and the social networks of
      all peers and major peers are small world networks. The analysis also confirms
      that peer social networks show in general disassortative correlations, except
      that active providers are connected between each other and by active requesters.
      The study presented in this paper gives a better understanding of peer
      relationships in resource sharing, which may help a better design of future P2P
      networks and open the path to the study of transport processes on top of real P2P
      topologies.

PMID- 16605615
TI  - Multiple phases in stochastic dynamics: geometry and probabilities.
AB  - Stochastic dynamics is generated by a matrix of transition probabilities. Certain
      eigenvectors of this matrix provide observables, and when these are plotted in
      the appropriate multidimensional space the phases (in the sense of phase
      transitions) of the underlying system become manifest as extremal points. This
      geometrical construction, which we call an observable representation of state
      space, can allow hierarchical structure to be observed. It also provides a method
      for the calculation of the probability that an initial points ends in one or
      another asymptotic state.

PMID- 16605616
TI  - Centrality measures in spatial networks of urban streets.
AB  - We study centrality in urban street patterns of different world cities
      represented as networks in geographical space. The results indicate that a
      spatial analysis based on a set of four centrality indices allows an extended
      visualization and characterization of the city structure. A hierarchical
      clustering analysis based on the distributions of centrality has a certain
      capacity to distinguish different classes of cities. In particular, self
      organized cities exhibit scale-free properties similar to those found in
      nonspatial networks, while planned cities do not.

PMID- 16605617
TI  - Nonequilibrium thermodynamics for open systems.
AB  - We develop the general equation for the nonequilibrium reversible-irreversible
      coupling (GENERIC) framework of nonequilibrium thermodynamics for open systems. A
      clear distinction between bulk and boundary contributions to the Poisson and
      dissipative brackets employed to generate reversible and irreversible
      contributions to time evolution from energy and entropy allows us to formulate
      the bulk equations as well as the exchange and interaction with the environment
      directly. The full brackets keep all the structure and hence the predictive power
      of the original GENERIC for isolated systems. The straightforward procedure is
      illustrated for hydrodynamics of open systems. Boltzmann's kinetic equation is
      discussed as a further example. In the Appendix, the thermodynamic treatment of
      surface excess variables at walls and their role in boundary conditions for the
      bulk variables is exemplified for a diffusion cell.

PMID- 16605618
TI  - Modeling bursts and heavy tails in human dynamics.
AB  - The dynamics of many social, technological and economic phenomena are driven by
      individual human actions, turning the quantitative understanding of human
      behavior into a central question of modern science. Current models of human
      dynamics, used from risk assessment to communications, assume that human actions
      are randomly distributed in time and thus well approximated by Poisson processes.
      Here we provide direct evidence that for five human activity patterns, such as
      email and letter based communications, web browsing, library visits and stock
      trading, the timing of individual human actions follow non-Poisson statistics,
      characterized by bursts of rapidly occurring events separated by long periods of
      inactivity. We show that the bursty nature of human behavior is a consequence of
      a decision based queuing process: when individuals execute tasks based on some
      perceived priority, the timing of the tasks will be heavy tailed, most tasks
      being rapidly executed, while a few experiencing very long waiting times. In
      contrast, priority blind execution is well approximated by uniform interevent
      statistics. We discuss two queuing models that capture human activity. The first
      model assumes that there are no limitations on the number of tasks an individual
      can handle at any time, predicting that the waiting time of the individual tasks
      follow a heavy tailed distribution P(tau(w)) approximately tau(w)(-alpha) with
      alpha=3/2. The second model imposes limitations on the queue length, resulting in
      a heavy tailed waiting time distribution characterized by alpha=1. We provide
      empirical evidence supporting the relevance of these two models to human activity
      patterns, showing that while emails, web browsing and library visitation display
      alpha=1, the surface mail based communication belongs to the alpha=3/2
      universality class. Finally, we discuss possible extension of the proposed
      queuing models and outline some future challenges in exploring the statistical
      mechanics of human dynamics.

PMID- 16605619
TI  - Optimal paths in strong and weak disorder: a unified approach.
AB  - We present a unified scaling theory for the optimal path connecting opposite
      edges of a disordered lattice of size L. Each bond of the lattice is assigned a
      cost exp(ar), where r is a uniformly distributed random variable and a is
      disorder strength. The optimal path minimizes the sum of the costs of the bonds
      along the path. We argue that for L>>a(nu) , where nu is the correlation exponent
      of percolation, the path becomes equivalent to a directed polymer on an effective
      lattice consisting of blobs of size xi=a(nu). It is self-affined and
      characterized by the roughness exponent of directed polymers chi. For L<<a(nu),
      or on the length scales below the blob size xi, the path behaves as an optimal
      path in the strong disorder limit. It has a self-similar fractal shape with
      fractal dimension d(opt). We derived the scaling relations for the length of the
      path, its transversal displacement, the average cost and its fluctuation. We test
      our scaling theoretical predictions by numerical simulations on a square lattice.

PMID- 16605620
TI  - Modeling cross correlations within a many-assets market.
AB  - A simple model for simulating cross correlations of a many-assets market is
      discussed. Correlations between assets are initially considered within the
      context of the well-known one-factor model, in which a driving term common to all
      stocks is present. The results are compared to those of real market data
      corresponding to a set of 445 stocks taken from the Standard and Poors 500 index.
      The model is further extended by introducing a stochastic volatility within each
      time series using an autoregressive scheme. This artificial market reproduces the
      empirically observed fat tails in the distribution function of logarithmic price
      variations and, more important, leads to additional cross correlations between
      the time series, in better agreement with the real market behavior.

PMID- 16605621
TI  - Critical behavior of an even-offspringed branching and annihilating random-walk
      cellular automaton with spatial disorder.
AB  - A stochastic cellular automaton exhibiting a parity-conserving class transition
      has been investigated in the presence of quenched spatial disorder by large-scale
      simulations. Numerical evidence has been found that weak disorder causes
      irrelevant perturbation for the universal behavior of the transition and the
      absorbing phase of this model. This opens up the possibility for experimental
      observation of the critical behavior of a nonequilibrium phase transition to
      absorbing state. For very strong disorder the model breaks up into blocks with
      exponential-size distribution and continuously changing critical exponents are
      observed. For strong disorder the randomly distributed diffusion walls introduce
      another transition within the inactive phase of the model, in which residual
      particles survive the extinction. The critical dynamical behavior of this
      transition has been explored.

PMID- 16605622
TI  - Critical exponents for the restricted sandpile.
AB  - I report large-scale Monte Carlo studies of a one-dimensional height-restricted
      stochastic sandpile using the quasistationary simulation method. Results for
      systems of up to 50 000 sites yield estimates for critical exponents that differ
      significantly from those obtained using smaller systems, but are consistent with
      recent predictions derived from a Langevin equation for stochastic sandpiles
      [Ramasco, Phys. Rev. E 69, 045105(R) (2004)]. This suggests that apparent
      violations of universality in one-dimensional sandpiles are due to strong
      corrections to scaling and finite-size effects.

PMID- 16605623
TI  - Network of European Union-funded collaborative research and development projects.
AB  - We describe collaboration networks consisting of research projects funded by the
      European Union (EU) and the organizations involved in those projects. The
      networks are substantial in terms of size, complexity, and potential impact on
      research policies and national economies in the EU. In empirical determinations
      of the network properties, we observe characteristics similar to those of other
      collaboration networks, including scale-free degree distributions, small
      diameter, and high clustering. We present some plausible models for the formation
      and structure of networks with the observed properties.

PMID- 16605624
TI  - Nonlinear dynamics in one dimension: a criterion for coarsening and its temporal
      law.
AB  - We develop a general criterion about coarsening for some classes of nonlinear
      evolution equations describing one-dimensional pattern-forming systems. This
      criterion allows one to discriminate between the situation where a coarsening
      process takes place and the one where the wavelength is fixed in the course of
      time. An intermediate scenario may occur, namely "interrupted coarsening." The
      power of the criterion on which a brief account has been given [Politi and
      Misbah, Phys. Rev. Lett. 92, 090601 (2004)], and which we extend here to more
      general equations, lies in the fact that the statement about the occurrence of
      coarsening, or selection of a length scale, can be made by only inspecting the
      behavior of the branch of steady state periodic solutions. The criterion states
      that coarsening occurs if lambda'(A)>0 while a length scale selection prevails if
      lambda'(A)<0, where lambda is the wavelength of the pattern and A is the
      amplitude of the profile (prime refers to differentiation). This criterion is
      established thanks to the analysis of the phase diffusion equation of the
      pattern. We connect the phase diffusion coefficient D(lambda) (which carries a
      kinetic information) to lambda'(A), which refers to a pure steady state property.
      The relationship between kinetics and the behavior of the branch of steady state
      solutions is established fully analytically. Another important and new result
      which emerges here is that the exploitation of the phase diffusion coefficient
      enables us to determine in a rather straightforward manner the dynamical
      coarsening exponent. Our calculation, based on the idea that |D(lambda)|
      approximately lambda2/t, is exemplified on several nonlinear equations, showing
      that the exact exponent is captured. We are not aware of another method that so
      systematically provides the coarsening exponent. Contrary to many situations
      where the one-dimensional character has proven essential for the derivation of
      the coarsening exponent, this idea can be used, in principle, at any dimension.
      Some speculations about the extension of the present results are outlined.

PMID- 16605625
TI  - Spacing distributions for point processes on a regular fractal.
AB  - The homogeneous Poisson point process in Rd (denoted by Pd) is a basic model of
      stochastic geometry and modern statistical physics. Using ideas from fractal
      geometry, geometrical statistics, and random matrix theory, we introduce the
      model of random points on a self-similar fractal as a model of intermediate
      statistics, in the sense that the interpoint spacing statistics of the model are
      intermediate between those of P1 and P2 when the fractal dimension is in between
      1 and 2, and intermediate between those of P2 and P3 when the fractal dimension
      is in between 2 and 3, and so on. We also introduce the idea of using a
      continuous family of such models to interpolate between P1 and P2 and thereby
      effectuate crossover transitions between P1 statistics and P2 statistics. We
      first derive the kth-nearest-neighbor spacing distribution for the general model,
      and then study the interpoint spacing statistics of several realizations of the
      model involving Sierpinski fractals in R2 and R3. We also study a realization of
      a continuous interpolation between P1 and P2, in particular a continuous
      interpolation between a point process on a line and a point process on a plane
      filling curve, using the continuous family of self-similar Koch curves in R2. In
      the latter study, we specifically analyze the second-nearest-neighbor interpoint
      spacing statistics, which undergo a crossover transition between semi-Poisson and
      Ginibre statistics.

PMID- 16605626
TI  - Spectral statistics in noninteracting many-particle systems.
AB  - It is widely accepted that the statistical properties of energy level spectra
      provide an essential characterization of quantum chaos. Indeed, the spectral
      fluctuations of many different systems like quantum billiards, atoms, or atomic
      nuclei have been studied. However, noninteracting many-body systems have received
      little attention, since it is assumed that they must exhibit Poisson-like
      fluctuations. Apart from a heuristic argument of Bloch, there are neither
      systematic numerical calculations nor a rigorous derivation of this fact. Here we
      present a rigorous study of the spectral fluctuations of noninteracting identical
      particles moving freely in a mean field emphasizing the evolution with the number
      of particles N as well as with the energy. Our results are conclusive. For N > or
      =2 the spectra of these systems exhibit Poisson fluctuations provided that we
      consider sufficiently high excitation energies. Nevertheless, when the mean field
      is chaotic there exists a critical energy scale L(c); beyond this scale, the
      fluctuations deviate from the Poisson statistics as a reminiscence of the
      statistical properties of the mean field.

PMID- 16605627
TI  - Coherent regimes of mutually coupled Chua's circuits.
AB  - We study the dynamical regimes that emerge from the strong coupling between two
      Chua's circuits with parameters mismatch. For the region around the perfect
      synchronous state we show how to combine parameter diversity and coupling in
      order to robustly and precisely target a desired regime. This target process
      allows us to obtain regimes that may lie outside parameter ranges accessible for
      any isolated circuit. The results are obtained by following a recently developed
      theoretical technique, the order parameter expansion, and are verified both by
      numerical simulations and on electronic circuits. The theoretical results
      indicate that the same predictable change in the collective dynamics can be
      obtained for large populations of strongly coupled circuits with parameter
      mismatches.

PMID- 16605628
TI  - Parametric invariant random matrix model and the emergence of multifractality.
AB  - We propose a random matrix modeling for the parametric evolution of eigenstates.
      The model is inspired by a large class of quantized chaotic systems. Its unique
      feature is having parametric invariance while still possessing the
      nonperturbative breakdown that had been discussed by Wigner 50 years ago. Of
      particular interest is the emergence of an additional crossover to
      multifractality.

PMID- 16605630
TI  - Geometric framework for phase synchronization in coupled noisy nonlinear systems.
AB  - A geometric approach is introduced for understanding the phenomenon of phase
      synchronization in coupled nonlinear systems in the presence of additive noise.
      We show that the emergence of cooperative behavior through a change of stability
      via a Hopf bifurcation entails the spontaneous appearance of a gauge structure in
      the system, arising from the evolution of the slow dynamics, but induced by the
      fast variables. The conditions for the oscillators to be synchronised in phase
      are obtained. The role of weak noise appears to be to drive the system towards a
      more synchronized behavior. Our analysis provides a framework to explain recent
      experimental observations on noise-induced phase synchronization in coupled
      nonlinear systems.

PMID- 16605629
TI  - Synchronization by reactive coupling and nonlinear frequency pulling.
AB  - We present a detailed analysis of a model for the synchronization of nonlinear
      oscillators due to reactive coupling and nonlinear frequency pulling. We study
      the model for the mean field case of all-to-all coupling, deriving results for
      the initial onset of synchronization as the coupling or nonlinearity increase,
      and conditions for the existence of the completely synchronized state when all
      the oscillators evolve with the same frequency. Explicit results are derived for
      the Lorentzian, triangular, and top-hat distributions of oscillator frequencies.
      Numerical simulations are used to construct complete phase diagrams for these
      distributions.

PMID- 16605631
TI  - Survival probability time distribution in dielectric cavities.
AB  - We study the survival probability time distribution (SPTD) in dielectric
      cavities. In a circular dielectric cavity the SPTD has an algebraic long time
      behavior, approximately t(-2) in both the TM and TE cases, but shows different
      short time behaviors due to the existence of the Brewster angle in the TE case
      where the short time behavior is exponential. The SPTD for a stadium-shaped
      cavity decays exponentially, and the exponent shows a relation of gamma
      approximately n(-2), n is the refractive index, and the proportional coefficient
      is obtained from a simple model of the steady probability distribution. We also
      discuss the SPTD for a quadrupolar deformed cavity and show that the long time
      behavior can be algebraic or exponential depending on the location of islands.

PMID- 16605632
TI  - Dynamics of strongly localized Lyapunov vectors in many-hard-disk systems.
AB  - The dynamics of the localized region of the Lyapunov vector for the largest
      Lyapunov exponent is discussed in quasi-one-dimensional hard-disk systems at low
      density. We introduce a hopping rate to quantitatively describe the movement of
      the localized region of the Lyapunov vector, and show that it is a decreasing
      function of the hopping distance, implying a spatial correlation of the localized
      regions. This behavior is explained quantitatively by a brick accumulation model
      derived from hard-disk dynamics in the low density limit, in which hopping of the
      localized Lyapunov vector is represented as the movement of the highest brick
      position. We also give an analytical expression for the hopping rate, which is
      obtained as a sum of probability distributions for brick height configurations
      between two separated highest brick sites. The results of these simple models are
      in good agreement with the simulation results for hard-disk systems.

PMID- 16605633
TI  - Persistence of chaos in a time-delayed-feedback controlled Duffing system.
AB  - This paper concerns global phase structures of a time-delayed-feedback controlled
      two-well Duffing system. The remains of a global stretch and fold structure along
      an unstable manifold, which develops from an unstable fixed point in function
      space, reveals that the global chaotic dynamics is inherited from the original
      system by the controlled system. The remains of the original chaotic dynamics
      causes a highly complicated domain of attraction for target orbits and a long
      chaotic transient before convergence.

PMID- 16605634
TI  - Semi-Poisson statistics in quantum chaos.
AB  - We investigate the quantum properties of a nonrandom Hamiltonian with a steplike
      singularity. It is shown that the eigenfunctions are multifractals and, in a
      certain range of parameters, the level statistics is described exactly by semi
      Poisson statistics (SP) typical of pseudointegrable systems. It is also shown
      that our results are universal, namely, they depend exclusively on the presence
      of the steplike singularity and are not modified by smooth perturbations of the
      potential or the addition of a magnetic flux. Although the quantum properties of
      our system are similar to those of a disordered conductor at the Anderson
      transition, we report important quantitative differences in both the level
      statistics and the multifractal dimensions controlling the transition. Finally,
      the study of quantum transport properties suggests that the classical singularity
      induces quantum anomalous diffusion. We discuss how these findings may be
      experimentally corroborated by using ultracold atoms techniques.

PMID- 16605635
TI  - Modified Bayesian approach for the reconstruction of dynamical systems from time
      series.
AB  - Some recent papers were concerned with applicability of the Bayesian
      (statistical) approach to reconstruction of dynamic systems (DS) from
      experimental data. A significant merit of the approach is its universality. But,
      being correct in terms of meeting conditions of the underlying theorem, the
      Bayesian approach to reconstruction of DS is hard to realize in the most
      interesting case of noisy chaotic time series (TS). In this work we consider a
      modification of the Bayesian approach that can be used for reconstruction of DS
      from noisy TS. We demonstrate efficiency of the modified approach for solution of
      two types of problems: (1) finding values of parameters of a known DS by noisy
      TS; (2) classification of modes of behavior of such a DS by short TS with
      pronounced noise.

PMID- 16605636
TI  - Scaling and universality in transition to synchronous chaos with local-global
      interactions.
AB  - We study the coupled-map lattice model with both local and global couplings. We
      find necessary conditions for observing synchronous chaos and investigate the
      transition to synchronization as a dynamic phase transition. We discover that
      this transition, if continuous, shows scaling and universal behavior with the
      dynamic exponent z = 2. We also define and illustrate an interesting quantity
      similar to persistence at critical point.

PMID- 16605637
TI  - Experimental synchronization of spatiotemporal chaos in nonlinear optics.
AB  - We demonstrate that a unidirectional coupling between a pattern forming system
      and its replica induces complete synchronization of the slave to the master
      system onto a spatiotemporal chaotic state.

PMID- 16605638
TI  - Collective dynamics in coupled maps on a lattice with quenched disorder.
AB  - It is investigated how a spatial quenched disorder modifies the dynamics of
      coupled map lattices. The disorder is introduced via the presence or absence of
      coupling terms among lattice sites. Two nonlinear maps have been considered
      embodying two paradigmatic dynamics. The Miller and Huse map can be associated
      with an Ising-type dynamics, whereas the logistic coupled maps is a prototype of
      a nontrivial collective dynamics. Various indicators quantifying the overall
      behavior, demonstrates that even a small amount of spatial disorder is capable to
      alter the dynamics found for purely ordered cases.

PMID- 16605639
TI  - Delayed feedback control of the Lorenz system: an analytical treatment at a
      subcritical Hopf bifurcation.
AB  - We develop an analytical approach for the delayed feedback control of the Lorenz
      system close to a subcritical Hopf bifurcation. The periodic orbits arising at
      this bifurcation have no torsion and cannot be stabilized by a conventional
      delayed feedback control technique. We utilize a modification based on an
      unstable delayed feedback controller. The analytical approach employs the center
      manifold theory and the near identity transformation. We derive the
      characteristic equation for the Floquet exponents of the controlled orbit in an
      analytical form and obtain simple expressions for the threshold of stability as
      well as for an optimal value of the control gain. The analytical results are
      supported by numerical analysis of the original system of nonlinear differential
      difference equations.

PMID- 16605640
TI  - Stability analysis of dynamical regimes in nonlinear systems with discrete
      symmetries.
AB  - We present a theorem that allows one to simplify the linear stability analysis of
      periodic and quasiperiodic nonlinear regimes in N-particle mechanical systems
      with different kinds of discrete symmetry. This theorem suggests a decomposition
      of the linearized system arising in the standard stability analysis into a number
      of subsystems whose dimensions can be considerably less than the dimension of the
      full system. As an example of such a simplification, we discuss the stability of
      bushes of modes (invariant manifolds) for the Fermi-Pasta-Ulam chains and prove
      another theorem about the maximal dimension of the above-mentioned subsystems.

PMID- 16605641
TI  - Geometry-induced pulse instability in microdesigned catalysts: the effect of
      boundary curvature.
AB  - We explore the effect of boundary curvature on the instability of reactive pulses
      in the catalytic oxidation of on microdesigned Pt catalysts. Using ring-shaped
      domains of various radii, we find that the pulses disappear (decollate from the
      inert boundary) at a turning point bifurcation, and we trace this boundary in
      both physical and geometrical parameter space. These computations corroborate
      experimental observations of pulse decollation.

PMID- 16605642
TI  - Entrainment of coupled oscillators on regular networks by pacemakers.
AB  - We study Kuramoto oscillators, driven by one pacemaker, on d-dimensional regular
      topologies with nearest neighbor interactions. We derive the analytical
      expressions for the common frequency in the case of phase-locked motion and for
      the critical frequency of the pacemaker, placed at an arbitrary position in the
      lattice, so that above the critical frequency no phase-locked motion is possible.
      We show that the mere change in topology from an open chain to a ring induces
      synchronization for a certain range of pacemaker frequencies and couplings, while
      keeping the other parameters fixed. Moreover, we demonstrate numerically that the
      critical frequency of the pacemaker decreases as a power of the linear size of
      the lattice with an exponent equal to the dimension of the system. This leads in
      particular to the conclusion that for infinite-dimensional topologies the
      critical frequency for having entrainment decreases exponentially with increasing
      size of the system, or, more generally, with increasing depth of the network,
      that is, the average distance of the oscillators from the pacemaker.

PMID- 16605643
TI  - Guiding chemical pulses through geometry: Y junctions.
AB  - We study computationally and experimentally the propagation of chemical pulses in
      complex geometries. The reaction of interest, CO oxidation, takes place on single
      crystal Pt(110) surfaces that are microlithographically patterned; they are also
      addressable through a focused laser beam, manipulated through galvanometer
      mirrors, capable of locally altering the crystal temperature and thus affecting
      pulse propagation. We focus on sudden changes in the domain shape (corners in a Y
      junction geometry) that can affect the pulse dynamics; we also show how brief,
      localized temperature perturbations can be used to control reactive pulse
      propagation. The computational results are corroborated through experimental
      studies in which the pulses are visualized using reflection anisotropy
      microscopy.

PMID- 16605644
TI  - Spirals and vortex lattices in quasi-self-imaging divide-by-three optical
      parametric oscillators.
AB  - A linear stability analysis is derived in self-imaging cavities for which the
      conditions for large Fresnel number are stated. In cases of both Fabry-Perot and
      ring cavities a Hopf bifurcation is predicted at finite transverse wave number.
      The self-imaging Fabry-Perot resonator operates as a longitudinal multimode
      cavity that invalidates the mean-field model. Above the bifurcation threshold,
      either vortex lattices, spirals, or targets occur, depending on the Fresnel
      number, the input intensity, and the mistunings. The time and spatial
      characteristics have different scales in the case of a self-imaging ring cavity,
      but the same sort of patterns are reported.

PMID- 16605645
TI  - Dynamic regimes of buoyancy-affected two-phase flow in unconsolidated porous
      media.
AB  - The invasion and subsequent flow of a nonwetting fluid (NWF) in a three
      dimensional, unconsolidated porous medium saturated with a wetting fluid of
      higher density and viscosity have been studied experimentally using a light
      transmission technique. Distinct dynamic regimes have been found for different
      relative magnitudes of viscous, capillary, and gravity forces. It is shown that
      the ratio of viscous and hydrostatic pressure gradients can be used as a relevant
      dimensionless number K for the characterization of the different flow regimes.
      For low values of K, the invasion is characterized by the migration and
      fragmentation of isolated clusters of the NWF resulting from the prevalence of
      gravity and capillary forces. At high values of K, the dominance of viscous and
      gravity forces leads to an anisotropic fingerlike invasion. When the invasion
      stops after the breakthrough of the NWF at the open upper boundary, the invasion
      structure retracts under the influence of gravity and transforms into stable
      vertical channels. It is shown that the stability of these channels is the result
      of a balance between hydrostatic and viscous pressure gradients.

PMID- 16605646
TI  - Measuring the transverse magnetization of rotating ferrofluids.
AB  - We report on measurements of the transverse magnetization of a ferrofluid
      rotating as a rigid body in a constant magnetic field, H0, applied perpendicular
      to the axis of rotation. The rotation of the fluid leads to a nonequilibrium
      situation, where the ferrofluid magnetization M and the magnetic field within the
      sample, H, are no longer parallel to each other. The off-axis magnetization
      perpendicular to H0 is measured as a function of both the applied magnetic field
      H0 and the angular frequency Omega. The latter ranges from a few hertz to
      frequencies well above a characteristic inverse Brownian relaxation time. Our
      experimental results strongly indicate that the transverse magnetization is
      caused only by a small fraction of the colloidal ferromagnetic particles. The
      effect of the polydispersity of the ferrofluid is discussed. Experimental results
      are compared to predictions based on several theoretical models. A single-time
      relaxation approach for the so-called effective field and a field-dependent Debye
      relaxation of M yield reasonably good shapes of the curves of transverse
      magnetization vs Omega. However, like the other models, they overestimate their
      magnitudes.

PMID- 16605647
TI  - Stretching and tilting of material lines in turbulence: the effect of strain and
      vorticity.
AB  - The Lagrangian evolution of infinitesimal material lines is investigated
      experimentally through three dimensional particle tracking velocimetry (3D-PTV)
      in quasihomogeneous turbulence with the Taylor microscale Reynolds number
      Re(lambda)=50. Through 3D-PTV we access the full tensor of velocity derivatives
      du(i)/dx(j) along particle trajectories, which is necessary to monitor the
      Lagrangian evolution of infinitesimal material lines l. By integrating the effect
      on l of (i) the tensor du(i)/dx(j), (ii) its symmetric part s(ij), (iii) its
      antisymmetric part r(ij), along particle trajectories, we study the evolution of
      three sets of material lines driven by a genuine turbulent flow, by "strain
      only," or by "vorticity only," respectively. We observe that, statistically,
      vorticity reduces the stretching rate l(i)l(j)s(ij)/l2, altering (by tilting
      material lines) the preferential orientation between l and the first (stretching)
      eigenvector lambda1 of the rate of strain tensor. In contrast, s(ij), in
      "absence" of vorticity, significantly contributes to both tilting and stretching,
      resulting in an enhanced stretching rate compared to the case of material lines
      driven by the full tensor du(i)/dx(j). The same trend is observed for the
      deformation of material volumes.

PMID- 16605648
TI  - Pore-network study of the mechanisms of foam generation in porous media.
AB  - Understanding the role of pore-level mechanisms is essential to the mechanistic
      modeling and simulation of foam processes in porous media. Three different pore
      level events can lead to foam formation: snapoff, leave behind, and lamella
      division. The initial state of the porous medium (fully saturated with liquid or
      already partially drained), as surfactant is introduced, also affects the
      different foam-generation mechanisms. Bubbles created by any of these mechanisms
      cause the formation of new bubbles by snapoff and leave behind as gas drains
      liquid-saturated pores. Lamellae are stranded unless the pressure gradient is
      sufficient to mobilize those that have been created. To appreciate the roles of
      these mechanisms, their interaction at the pore-network level was studied. We
      report an extensive pore-network study that incorporates the above pore-level
      mechanisms, as foam is created by drainage or by the continuous injection of gas
      and liquid in porous media. Pore networks with up to 10 000 pores are considered.
      The study explores the roles of the pore-level events, and by implication, the
      appropriate form of the foam-generation function for mechanistic foam simulation.
      Results are compared with previous studies. In particular, the network
      simulations reconcile an apparent contradiction in the foam-generation model of
      Rossen and Gauglitz [AIChE J. 36, 1176 (1990)], and identify how foam is created
      near the inlet of the porous medium when lamella division controls foam
      generation. In the process, we also identify a new mechanism of snap-off and foam
      generation near the inlet of the medium.

PMID- 16605649
TI  - Geodesic network method for flows between two rough surfaces in contact.
AB  - A discrete network method based on previous asymptotic analysis for computing
      fluid flows between confined rough surfaces is proposed. This random
      heterogeneous geodesic network method could be either applied to surfaces
      described by a continuous random field or finely discretized on a regular grid.
      This method tackles the difficult problem of fluid transport between rough
      surfaces in close contact. We describe the principle of the method as well as
      detail its numerical implementation and performances. Macroscopic conductances
      are computed and analyzed far from the geometrical percolation threshold.
      Numerical results are successfully compared with the effective medium
      approximation, the application of which is also studied analytically.

PMID- 16605650
TI  - Bubble behavior in a Taylor vortex.
AB  - We present a study on the behavior of air bubbles captured in a Taylor vortex
      formed in the annulus between two concentric cylinders. It is found that small
      bubbles stay either at certain locations near the vortex cores or in the outflow
      regions along the inner cylinder. If bubbles of the same size are introduced, a
      variety of bubble structures (such as ring, chain, cluster, etc.) appear due to
      different mechanisms. For bubbles of nonuniform size, orbit crossing of small and
      large bubbles is observed. Droplets and particles can also be captured in Taylor
      vortices, and these exhibit certain unique features.

PMID- 16605651
TI  - Wavelet multiresolution analysis of the three vorticity components in a turbulent
      far wake.
AB  - The main objective of the present study is to examine the characteristics of the
      vortical structures in a turbulent far wake using the wavelet multiresolution
      technique by decomposing the vorticity into a number of orthogonal wavelet
      components based on different central frequencies. The three vorticity components
      were measured simultaneously using an eight-wire probe at three Reynolds numbers,
      namely 2000, 4000, and 6000. It is found that the dominant contributions to the
      vorticity variances are from the intermediate and relatively small-scale
      structures. The contributions from the large and intermediate-scale structures to
      the vorticity variances decrease with the increase of Reynolds number. The
      contributions from the small-scale structures to all three vorticity variances
      jump significantly when Reynolds number is changed from 2000 to 4000, which is
      connected to previous observations in the near wake that there is a significant
      increase in the generation of small-scale structures once the Reynolds number
      reaches about 5000. This result reinforces the conception that turbulence
      "remembers" its origin.

PMID- 16605652
TI  - Drag reduction by compressible bubbles.
AB  - Drag reduction by bubbles in stationary turbulent flows is sensitive to the
      compressibility of the bubbles. Without this dynamical effect the bubbles only
      renormalize the fluid density and viscosity, an effect that by itself can only
      lead to a small percentage of drag reduction. We show in this paper that the
      dynamics of bubbles and their effect on the compressibility of the mixture can
      lead to a much higher drag reduction.

PMID- 16605653
TI  - Stretching of a confined ferrofluid: influence of viscous stresses and magnetic
      field.
AB  - An analytical investigation is presented for the stretch flow of a viscous
      Newtonian ferrofluid highly confined between parallel plates. We focus on the
      development of interfacial instabilities when the upper plate is lifted at a
      described rate, under the action of an applied magnetic field. We derive the mode
      coupling differential equation for the interface perturbation amplitudes and
      study both linear and nonlinear flow regimes. In contrast to the great majority
      of works in stretch flow we take into account stresses originated from velocity
      gradients normal to the ferrofluid interface. The impact of such normal stresses
      is accounted for through a modified Young-Laplace pressure jump interfacial
      boundary condition, which also includes the contribution from magnetic normal
      traction. We study how the stability properties of the interface and the shape of
      the emerging patterns respond to the combined action of normal stresses and
      magnetic field, both in the presence and absence of surface tension. We show that
      the inclusion of normal viscous stresses introduces a pertinent dependence on the
      initial aspect ratio, indicating that the number of fingers formed would be
      overestimated if such stresses are not taken into account. At early linear stages
      it is found that such stresses regularize the system, acting as an effective
      interfacial tension. At weakly nonlinear stages we verified that normal stresses
      reduce finger competition, which can be completely suppressed with the assistance
      of an azimuthal magnetic field. We have also found that the magnetic normal
      traction introduces a purely nonlinear contribution to the problem, revealing the
      key role played by the magnetic susceptibility in the control of finger
      competition.

PMID- 16605654
TI  - Multiscale character of the nonlinear coherent dynamics in the Rayleigh-Taylor
      instability.
AB  - We report nonlinear solutions for a system of conservation laws describing the
      dynamics of the large-scale coherent structure of bubbles and spikes in the
      Rayleigh-Taylor instability (RTI) for fluids with a finite density ratio. Three
      dimensional flows are considered with general type of symmetry in the plane
      normal to the direction of gravity. The nonlocal properties of the interface
      evolution are accounted for on the basis of group theory. It is shown that
      isotropic coherent structures are stable. For anisotropic structures, secondary
      instabilities develop with the growth rate determined by the density ratio. For
      stable structures, the curvature and velocity of the nonlinear bubble have
      nontrivial dependencies on the density ratio, yet their mutual dependence on one
      another has an invariant form independent of the density ratio. The process of
      bubble merge is not considered. Based on the obtained results we argue that the
      large-scale coherent dynamics in RTI has a multiscale character and is governed
      by two length scales: the period of the coherent structure and the bubble (spike)
      position.

PMID- 16605655
TI  - Topological mixing with ghost rods.
AB  - Topological chaos relies on the periodic motion of obstacles in a two-dimensional
      flow in order to form nontrivial braids. This motion generates exponential
      stretching of material lines, and hence efficient mixing. Boyland, Aref, and
      Stremler [J. Fluid Mech. 403, 277 (2000)] have studied a specific periodic motion
      of rods that exhibits topological chaos in a viscous fluid. We show that it is
      possible to extend their work to cases where the motion of the stirring rods is
      topologically trivial by considering the dynamics of special periodic points that
      we call "ghost rods", because they play a similar role to stirring rods. The
      ghost rods framework provides a new technique for quantifying chaos and gives
      insight into the mechanisms that produce chaos and mixing. Numerical simulations
      for Stokes flow support our results.

PMID- 16605656
TI  - Supercritical fluids in porous composite materials: direction-dependent flow
      properties.
AB  - The results of extensive nonequilibrium molecular dynamics simulations of flow
      and transport of a pure fluid, as well as a binary fluid mixture, through a
      porous material composed of a macropore, a mesopore, and a nanopore, in the
      presence of an external pressure gradient, are reported. We find that under
      supercritical conditions, unusual phenomena occur that give rise to direction
      dependent and pressure-dependent permeabilities for the fluids' components. The
      results, which are also in agreement with a continuum formulation of the problem,
      indicate that the composite nature of the material, coupled with condensation,
      give rise to the direction-dependent permeabilities. Therefore, modeling flow and
      transport of fluids, in the supercritical regime, in porous materials with the
      type of morphology considered in this paper (such as supported porous membranes)
      would require using effective permeabilities that depend on both the external
      pressure drop and the direction along which it is applied to the materials.

PMID- 16605657
TI  - Equilibrium theory of coherent vortex and zonal jet formation in a system of
      nonlinear Rossby waves.
AB  - The problem of coherent vortex and zonal jet formation in a system of oceanic or
      planetary nonlinear Rossby waves is considered from the point of view of the late
      time steady state achieved by free decay of a given initial state. Statistical
      equilibrium equations respecting all conservation laws are constructed for a
      broad class of models, generalizing those derived previously for two-dimensional
      inviscid Euler flow. Jetlike solutions are ubiquitous, with large coherent
      vortices existing only when there is a background flow whose velocity locally
      cancels the beta effect.

PMID- 16605658
TI  - Light-induced deformation and instability of a liquid interface. I. Statics.
AB  - We study in detail the deformations of a liquid-liquid interface induced by the
      electromagnetic radiation pressure of a focused cw laser beam. Using a simple
      linear model of static equilibrium of the interface under the effect of radiation
      pressure, buoyancy, and Laplace pressure, we explain the observed hump height
      variations for any value of the optical Bond number Bo=(omega0/lc)2 (lc is the
      capillary length and omega0 is the waist of the beam) in the regime of weak
      deformations and show that the deformations are independent of the direction of
      propagation of the laser. By increasing the beam power, we observe an instability
      of the interface leading to the formation of a long jet when the laser propagates
      from the more refringent phase to the less refringent one. We propose that the
      total internal reflection of the incident light on the highly deformed interface
      could be at the origin of this instability. Using a nonlinear model of static
      equilibrium of the interface taking account of the angular dependance of
      radiation pressure, we explain the measured beam power threshold of the
      instability P, as well as the shape of the interface deformations observed at
      large waists just below the instability onset. According to this model, the
      instability should occur when the interface slope reaches the angle of total
      reflection, theta(TR). We find experimentally that, just below the instability
      threshold, the maximum incidence angle along the interface, theta(imax), is
      significantly smaller than theta(TR) and that our nonlinear model does not
      present any instability up to theta(imax)=theta(TR). Thus, although the proposed
      instability model correctly predicts the instability threshold P, it fails to
      describe the actual instability mechanism. We finally discuss possible additional
      effects that could explain the instability.

PMID- 16605659
TI  - Light-induced deformation and instability of a liquid interface. II. Dynamics.
AB  - We study the dynamics of the deformation of a soft liquid-liquid interface by the
      optical radiation pressure of a focused cw Gaussian laser beam. We measured the
      temporal evolution of both the hump height and the hump curvature by direct
      observation and by detecting the focusing effect of the hump acting as a lens.
      Extending the results of Yoshitake [J. Appl. Phys. 97, 024901 (2005)] to the case
      of liquid-liquid interfaces and to the Bo approximately =1 regime
      [Bo=(omega0/lc)2, , where omega0 is the beam waist and lc the capillary length],
      we show that, in the Bo<<1 and Bo approximately =1 ranges, the small-amplitude
      deformations are correctly described by a linear hydrodynamic theory predicting
      an overdamped dynamics. We also study the dynamics of the large-amplitude
      interface deformations at the onset of optohydrodynamic instability [Phys. Rev.
      Lett. 90, 144503 (2003)]. Using a simple, phenomenological model for the
      nonlinear evolution of the hump height, we interpret the observed interface
      dynamics at the instability onset as the signature of an imperfect subcritical
      instability.

PMID- 16605660
TI  - Lattice-Boltzmann modeling of dissolution phenomena.
AB  - In this work, we present a lattice-Boltzmann model for the simulation of complex
      dissolution phenomena. We design boundary conditions to impose a fixed
      concentration or a surface flux for use in multicomponent lattice-Boltzmann
      models. These conditions can be applied to simulate complex reactive flow
      phenomena, e.g., in porous media. By combining the boundary conditions with a
      volume-of-fluid description of solid structures, the application area of the
      presented model is extended toward complex dissolution phenomena. The boundary
      conditions and the dissolution model are validated using benchmark problems with
      analytical solutions. The agreement is good in all tested cases.

PMID- 16605661
TI  - Amplitude modulation and relaxation-oscillation of counterpropagating rolls
      within a broken-symmetry laser-induced electroconvection strip.
AB  - We report a liquid-crystal pattern-formation experiment in which we break the
      lateral (translational) symmetry of a nematic medium with a laser-induced thermal
      gradient. The work is motivated by an improved measurement (reported here) of the
      temperature dependence of the electroconvection threshold voltage in planar
      nematic 4-methoxybenzylidene-4-butylaniline. In contrast with other broken
      symmetry-pattern studies that report a uniform drift, we observe a strip of
      counterpropagating rolls that collide at a sink point, and a strong temporally
      periodic amplitude modulation within a width of 3-4 rolls about the sink point.
      The time dependence of the amplitude at a fixed position is periodic but displays
      a nonsinusoidal relaxation-oscillation profile. After reporting experimental
      results based on spacetime contours and wave number profiles, along with a
      measurement of the change in the drift frequency with applied voltage at a fixed
      control parameter, we propose some potential guidelines for a theoretical model
      based on saddle-point solutions for Eckhaus-unstable states and coupled complex
      Ginzburg-Landau equations.

PMID- 16605662
TI  - Static and dynamic conductivity of warm dense matter within a density-functional
      approach: application to aluminum and gold.
AB  - The conductivity sigma(omega) of dense Al and Au plasmas is considered where all
      the needed inputs are obtained from density-functional theory (DFT). These
      calculations involve a self-consistent determination of (i) the equation of state
      and the ionization balance, (ii) evaluation of the ion-ion and ion-electron pair
      distribution functions, (iii) determination of the scattering amplitudes, and
      finally the conductivity. We present results for Al and Au for compressions 0.1
      2.0, and in the temperature range T=0.1-10 eV. Excellent agreement with recent
      first-principles calculations using multi-ion density-functional molecular
      dynamics is obtained where the data fields overlap. We review first-principles
      approaches to the optical conductivity, including many-body perturbation theory,
      molecular-dynamics evaluations, and simplified time-dependent DFT. The
      modification to the Drude conductivity in the presence of shallow bound states in
      typical Al plasmas is examined and numerical results are given at the level of
      the Fermi Golden Rule and an approximate time-dependent DFT.

PMID- 16605663
TI  - Negative ion behavior in single- and dual-frequency plasma etching reactors:
      particle-in-cell/Monte Carlo collision study.
AB  - Particle-in-cell/Monte Carlo simulations are used to simulate the trajectories
      and energies of randomly sampled F- and CF-(3) ions in capacitively coupled radio
      frequency discharges, in order to clarify the movement of the negative ions in
      the sheaths and plasma in both single- and dual-frequency regimes, as well as in
      symmetric and asymmetric discharges. In the single-frequency reactor both types
      of negative ions are confined in the plasma and the main loss mechanism is
      recombination with positive ions. In the dual-frequency reactor under certain
      operating conditions when the sheaths are wide and the bulk plasma is narrow the
      light F- ions move across from one sheath to the other, and they can even be lost
      at the electrodes. The main loss mechanisms are then electron detachment and
      absorption at the electrodes. The much heavier CF-(3) ions are still confined in
      the bulk and represent the major negative charge. In an asymmetric discharge the
      electric field in the sheath to the smaller (powered) electrode is much stronger
      than that in the sheath to the grounded electrode. Consequently, the F- ions
      reach mainly the grounded electrode.

PMID- 16605664
TI  - Transitions to spatiotemporal chaos and turbulence of flute instabilities in a
      magnetized plasma.
AB  - The spatiotemporal transition scenario of flute instabilities from a regular to a
      turbulent state is experimentally investigated in the plasma column of a
      thermionic discharge. The same transition scenario, i.e., the Ruelle-Takens route
      to turbulence, is found for both the Kelvin-Helmholtz and the Rayleigh-Taylor
      instabilities. It is demonstrated that the transition can be more or less smooth,
      according to the discharge mode. In both cases, a strong radial dependence is
      observed, which is linked to the velocity shear layer in the case of the Kelvin
      Helmholtz instability.

PMID- 16605665
TI  - Parametric instability in the formation of plasma waveguides.
AB  - Plasma waveguides generated by focusing a moderate intensity laser into neutral
      gas with an axicon lens can be unstable to the generation of axial modulations in
      the channel parameters. A model is proposed in which the modulations are due to
      the nonlinear coupling between the axicon field and a scattered mode in the
      evolving channel. Good agreement is found with experimental measurements of these
      modulations.

PMID- 16605666
TI  - Be I isoelectronic ions embedded in hot plasma.
AB  - The influence of plasma screening on the 2s(2 1)S0-->2s2p(3)p(0)1
      intercombination and the 2s(2 1)S0-->2s2p(1)p(0)1 allowed transitions is
      investigated theoretically for several ions along the isoelectronic sequence (C
      III, N IV, O V, Si XI, Fe XXIII, and Mo XXXIX). For the case of a weakly coupled
      hot plasma, multiconfiguration Dirac-Fock computations have been carried out for
      these ions by considering a (time averaged) Debye-Huckel potential for both the
      "electron-nucleus" and "electron-electron" interaction. The plasma screening is
      found to enlarge the 2s(2 1)S0-->2s2p(3)p(0)1 excitation energy uniformly along
      the Be I isoelectronic sequence, leading to an increasing blueshift of this
      intercombination line as the nuclear charge is increased. For the 2s(2 1)S0-
      >2s2p(1)p(0)1 resonance line, in contrast, the transition energy is either
      blueshifted or redshifted in dependence of the screening parameter and owing to a
      cancellation of the plasma screening on the electron-nucleus and electron
      electron interaction. This interplay of the (external) plasma screening with the
      internal interactions in the berylliumlike ions leads, for instance, to a shift
      of the resonance transition from red to blue in going from O V to Si XI ions.
      Apart from the screening effects on the transition energies, we also investigate
      their influence on the oscillator strengths and emission rates along the Be I
      isoelectronic sequence.

PMID- 16605667
TI  - Particle-in-cell Monte Carlo simulations of an extreme ultraviolet radiation
      driven plasma.
AB  - A self-consistent kinetic particle-in-cell model has been developed to describe a
      radiation driven plasma. Collisions between charged species and the neutral
      background are represented statistically by Monte Carlo collisions. The weakly
      ionized plasma is formed when extreme ultraviolet radiation coming from a pulsed
      discharge photoionizes a low pressure argon gas. The presence of a plasma close
      to optical components is potentially dangerous in case the ions that are
      accelerated in the plasma sheath gain enough energy to sputter the optics. The
      simulations predict the plasma parameters and notably the energy at which ions
      impact on the plasma boundaries. Finally, sputter rates are estimated on the
      basis of two sputtering models.

PMID- 16605668
TI  - Observation of strong correlation between quasimonoenergetic electron beam
      generation by laser wakefield and laser guiding inside a preplasma cavity.
AB  - We use a one-shot measurement technique to study effects of laser prepulses on
      the electron laser wakefield acceleration driven by relativistically intense
      laser pulses (lambda=790 nm, 11 TW, 37 fs) in dense helium gas jets. A
      quasimonoenergetic electron bunch with an energy peak approximately 11.5
      MeV[DeltaE/E approximately 10% (FWHM)] and with a narrow-cone angle (0.04pi mm
      mrad) of ejection is detected at a plasma density of 8 x 10(19) cm(-3). A strong
      correlation between the generation of monoenergetic electrons and optical guiding
      of the pulse in a thin channel produced by picosecond laser prepulses is
      observed. This generation mechanism is well corroborated by two-dimensional
      particle-in-cell simulations.

PMID- 16605669
TI  - Single-cycle high-intensity electromagnetic pulse generation in the interaction
      of a plasma wakefield with regular nonlinear structures.
AB  - The interaction of regular nonlinear structures (such as subcycle solitons,
      electron vortices, and wake Langmuir waves) with a strong wake wave in a
      collisionless plasma can be exploited in order to produce ultrashort
      electromagnetic pulses. The electromagnetic field of the nonlinear structure is
      partially reflected by the electron density modulations of the incident wake wave
      and a single-cycle high-intensity electromagnetic pulse is formed. Due to the
      Doppler effect the length of this pulse is much shorter than that of the
      nonlinear structure. This process is illustrated with two-dimensional particle-in
      cell simulations. The considered laser-plasma interaction regimes can be achieved
      in present day experiments and can be used for plasma diagnostics.

PMID- 16605670
TI  - Real-time study of fast-electron transport inside dense hot plasmas.
AB  - We offer a method to study transport of fast electrons in dense hot media. The
      technique relies on temporal profiling of the laser induced magnetic fields and
      offers a unique capability to map the hot electron currents and their
      neutralization (or lack of it) by the return currents in the plasma. We report
      direct quantitative measurements of strong electric inhibition in insulators and
      turbulence induced anomalous stopping of hot electrons in conductors. The present
      technique can prove extremely important from the point of view of fast ignition
      scheme, which relies on the penetration of fast electrons into the fusion core.

PMID- 16605671
TI  - Experimental demonstration of the Rayleigh acoustic viscous boundary layer
      theory.
AB  - Amplitude and phase velocity measurements on the laminar oscillatory viscous
      boundary layer produced by acoustic waves are presented. The measurements were
      carried out in acoustic standing waves in air with frequencies of 68.5 and 114.5
      Hz using laser Doppler anemometry and particle image velocimetry. The results
      obtained by these two techniques are in good agreement with the predictions made
      by the Rayleigh viscous boundary layer theory and confirm the existence of a
      local maximum of the velocity amplitude and its expected location.

PMID- 16605672
TI  - Decreased group velocity in compositionally graded films.
AB  - A theoretical formalism is presented that describes the group velocity of
      electromagnetic signals in compositionally graded films. The theory is first
      based on effective medium approximation or the Maxwell-Garnett approximation to
      obtain the equivalent dielectric function in a z slice. Then the effective
      dielectric tensor of the graded film is directly determined, and the group
      velocities for ordinary and extraordinary waves in the film are derived. It is
      found that the group velocity is sensitively dependent on the graded profile. For
      a power-law graded profile f(x)=ax(m), increasing m results in the decreased
      extraordinary group velocity. Such a decreased tendency becomes significant when
      the incident angle increases. Therefore the group velocity in compositionally
      graded films can be effectively decreased by our suitable adjustment of the total
      volume fraction, the graded profile, and the incident angle. As a result, the
      compositionally graded films may serve as candidate material for realizing small
      group velocity.

PMID- 16605673
TI  - Large enhancement of interface second-harmonic generation near the zero-n(-) gap
      of a negative-index Bragg grating.
AB  - We predict a large enhancement of interface second-harmonic generation near the
      zero-n(-) gap of a Bragg grating made of alternating layers of negative- and
      positive-index materials. Field localization and coherent oscillations of the
      nonlinear dipoles located at the structure's interfaces conspire to yield
      conversion efficiencies at least an order of magnitude greater than those
      achievable in the same length of nonlinear, phase-matched bulk material. These
      findings thus point to a new class of second-harmonic-generation devices made of
      standard centrosymmetric materials.

PMID- 16605674
TI  - Spatial correlation functions of inhomogeneous random electromagnetic fields.
AB  - We analyze the influence of an infinite planar perfectly conducting surface on
      the spatial correlation functions of a random quasimonochromatic classical
      electromagnetic vector field, based on a TE/TM decomposition of an angular
      spectrum of random plane waves. The presence of the surface causes the
      correlation to depend on both the absolute and relative locations of the field
      points (inhomogeneous correlation). Known asymptotic results for statistically
      homogeneous random free fields are retrieved as special cases. The analytical
      results are illustrated with computations for separations that are either
      perpendicular or parallel to the surface. The correlation distance for any field
      component exhibits a damped oscillatory dependency on the local center point. A
      geometric interpretation in terms of fluctuations of correlation cells is given.

PMID- 16605675
TI  - Analysis of surface plasmon modes and band structures for plasmonic crystals in
      one and two dimensions.
AB  - In this study, we employ the interfacial operator approach to compute surface
      plasmon modes as well as band structures (including longitudinal modes) for
      plasmonic crystals in one and two dimensions. In particular, we consider the free
      electron model for the metal. It is shown that the localized feature of surface
      plasmon modes can be resolved near the interface by introducing interfacial
      variables. For a one-dimensional array of metal, convergence of two branches of
      surface plasmon modes is studied by varying the filling fraction of the metal.
      For two-dimensional metallic structures, band flattening, band broadening, and
      plasmonic band gaps are observed and discussed. The highly degenerate nature and
      infinite number of surface plasmon modes can be explained by employing the
      Rayleigh quotient for the TE modes. The cutoff behavior in the TM modes is made
      clear by considering the energy density of the electromagnetic fields. The
      transverse electric fields, surface charges, and polarization currents are
      visualized to help understand various properties of surface plasmon modes.
      Moreover, the effect of plasma frequency and the transition from dispersive
      metals to perfect conductors are also explored. Finally, the contribution of
      Drude damping is considered by perturbation analysis.

PMID- 16605676
TI  - Photonic band mixing in linear chains of optically coupled microspheres.
AB  - The paper deals with optical excitations arising in a one-dimensional chain of
      identical spheres due to optical coupling of whispering gallery modes (WGM). The
      band structure of these excitations depends significantly on the intermixing
      between WGMs characterized by different values of angular quantum number, l. We
      develop a general theory of the photonic band structure of these excitations
      taking these effects into account and applied it to several cases of recent
      experimental interest. In the case of bands originating from WGMs with the
      angular quantum number of the same parity, the calculated dispersion laws are in
      good qualitative agreement with recent experiment results. Bands resulting from
      hybridization of excitations resulting from whispering gallery modes with
      different parity of l exhibits anomalous dispersion properties characterized by a
      gap in the allowed values of wave numbers and divergence of group velocity.

PMID- 16605677
TI  - Generalized nonlinear Schrodinger equation and ultraslow optical solitons in a
      cold four-state atomic system.
AB  - We investigate the influence of high-order dispersion and nonlinearity on the
      propagation of ultraslow optical solitons in a lifetime broadened four-state
      atomic system under a Raman excitation. Using a standard method of multiple
      scales we derive a generalized nonlinear Schrodinger equation and show that for
      realistic physical parameters and at the pulse duration of 10(-6)s, the effects
      of third-order linear dispersion, nonlinear dispersion, and delay in nonlinear
      refractive index can be significant and may not be considered as perturbations.
      We provide exact soliton solutions for the generalized nonlinear Schrodinger
      equation and demonstrate that optical solitons obtained may still have ultraslow
      propagating velocity. Numerical simulations on the stability and interaction of
      these ultraslow optical solitons in the presence of linear and differential
      absorptions are also presented.

PMID- 16605678
TI  - Solitons in the Salerno model with competing nonlinearities.
AB  - We consider a lattice equation (Salerno model) combining onsite self-focusing and
      intersite self-defocusing cubic terms, which may describe a Bose-Einstein
      condensate of dipolar atoms trapped in a strong periodic potential. In the
      continuum approximation, the model gives rise to solitons in a finite band of
      frequencies, with sechlike solitons near one edge, and an exact peakon solution
      at the other. A similar family of solitons is found in the discrete system,
      including a peakon; beyond the peakon, the family continues in the form of
      cuspons. Stability of the lattice solitons is explored through computation of
      eigenvalues for small perturbations, and by direct simulations. A small part of
      the family is unstable (in that case, the discrete solitons transform into robust
      pulsonic excitations); both peakons and cuspons are stable. The Vakhitov
      Kolokolov criterion precisely explains the stability of regular solitons and
      peakons, but does not apply to cuspons. In-phase and out-of-phase bound states of
      solitons are also constructed. They exchange their stability at a point where the
      bound solitons are peakons. Mobile solitons, composed of a moving core and
      background, exist up to a critical value of the strength of the self-defocusing
      intersite nonlinearity. Colliding solitons always merge into a single pulse.

PMID- 16605679
TI  - Magnetic plasmon resonance.
AB  - It is demonstrated that metallic horseshoe-shaped (also referred to as u-shaped)
      nanostructures can exhibit a magnetic resonance in the optical spectral range.
      This magnetic plasmon resonance is distinct from the purely geometric LC
      resonance occurring in perfectly conducting split rings because the plasmonic
      nature of the metal plays the dominant role. Similarly to the electrical surface
      plasmon resonance, the magnetic plasmon resonance is determined primarily by the
      metal properties and nanostructure geometry rather than by the ratio of the
      wavelength and the structure's size. Magnetic plasmon resonance occurs in
      nanostructures much smaller in size than the optical wavelength. Electromagnetic
      properties of periodically assembled horseshoe-shaped nanostructures are
      investigated, and the close proximity of the electrical and magnetic plasmon
      resonances is exploited in designing a negative index metamaterial. Close to the
      magnetic plasmon resonance frequency both magnetic permeability mu and electric
      permittivity epsilon can become negative, paving the way for the development of
      subwavelength negative index materials in the optical range.

PMID- 16605680
TI  - Transport and localization amongst coupled substructures.
AB  - The dynamics of the transport of the mean-square diffuse wave amplitude among
      coupled substructures is examined. Applications include coupled quantum dots,
      reverberation rooms, and chaotic billiards. A self-consistent theory is found to
      predict classical diffusive behavior at strong coupling, but to predict
      localization when coupling times are comparable to or greater than Heisenberg
      times. Predictions are compared to an exact result, to the Vollhardt-Wolfle self
      consistent theory for multiply scattering continua, and to direct numerical
      simulations.

PMID- 16605681
TI  - Generalization of the deflection angle in the classical scattering of particles.
AB  - Current conventions define the deflection angle associated with the classical
      elastic scattering of particles in terms of the system's position vector. This is
      not consistent with the definition of the scattering angle, a function of the
      momentum vector. A definition of the deflection angle which resolves this
      inconsistency is introduced and developed for the case of an arbitrary potential
      in two dimensions. It is shown that the generalized deflection angle reduces to
      that of Cross [J. Chem. Phys. 49, 609 (1967)] when angular momentum is conserved.
      An efficient algorithm for the calculation of the generalized deflection angle is
      given and its utility in the analysis of collision dynamics is demonstrated with
      a numerical example.

PMID- 16605682
TI  - Method to determine cutoff frequencies for acoustic waves propagating in
      nonisothermal media.
AB  - A method to determine cutoff frequencies for linear acoustic waves propagating in
      nonisothermal media is introduced. The developed method is based on wave variable
      transformations that lead to Klein-Gordon equations, and the oscillation theorem
      is applied to obtain the turning point frequencies. Physical arguments are used
      to justify the choice of the largest turning point frequency as the cutoff
      frequency. The method is used to derive the cutoff frequencies in nonisothermal
      media modeled by exponential and power law temperature gradients, for which the
      cutoffs cannot be obtained based on known analytical solutions. An interesting
      result is that the acoustic cutoff frequencies calculated by the method are local
      quantities that vary in the media, and that their specific values at a given
      height determine the frequency that acoustic waves must have in order to be
      propagating at this height. To extend this physical interpretation of the
      acoustic cutoff frequency to nonisothermal media of arbitrary temperature
      gradients, a generalized version of the method applicable to these media is also
      presented.

PMID- 16605683
TI  - Frequency-selective absorption characteristics of a metal surface with embedded
      dielectric microspheres.
AB  - The coupling of the resonances of spherical particles embedded near the surface
      of a metal and the surface plasmon is investigated by calculations using a
      multiple scattering formalism. The system we considered is a periodic array of
      glass spheres buried just beneath the surface of an Ag substrate. The calculated
      absorption spectra show features that can be traced to the resonance frequency of
      the microsphere cavity or the surface mode of the metal. In general, the
      absorption peaks for both the cavity and the surface mode are relatively weak
      when their resonance frequencies are far from each other. However, if the system
      is designed such that the cavitylike mode and the surface mode have almost the
      same frequency, the coupling of the resonances will lead to enhanced frequency
      selective absorption. Such systems can be employed to modify or control thermal
      emission.

PMID- 16605684
TI  - Nonlocal description of X waves in quadratic nonlinear materials.
AB  - We study localized light bullets and X waves in quadratic media and show how the
      notion of nonlocality can provide an alternative simple physical picture of both
      types of multidimensional nonlinear waves. For X waves we show that a local
      cascading limit in terms of a nonlinear Schrodinger equation does not exist-one
      needs to use the nonlocal description, because the nonlocal response function
      does not converge toward a function. Also, we use the nonlocal theory to show
      that the coupling to the second harmonic is able to generate an X shape in the
      fundamental field despite having anomalous dispersion, in contrast to the
      predictions of the cascading limit.

PMID- 16605685
TI  - Two-dimensional solitons in saturable media with a quasi-one-dimensional lattice
      potential.
AB  - We study families of solitons in a two-dimensional model of the light
      transmission through a photorefractive medium equipped with a (quasi-)one
      dimensional photonic lattice. The soliton families are bounded from below by
      finite minimum values of the peak and total power. Narrow solitons have a single
      maximum, while broader ones feature side lobes. Stability of the solitons is
      checked by direct simulations. The solitons can be set in motion across the
      lattice (actually, made tilted in the spatial domain), provided that the
      respective boost parameter does not exceed a critical value. Collisions between
      moving solitons are studied too. Collisions destroy the solitons, unless their
      velocities are sufficiently small. In the latter case, the colliding solitons
      merge into a single stable pulse.

PMID- 16605686
TI  - Method of images in optical discrete systems.
AB  - We show that optical wave propagation in discrete boundary geometries can be
      effectively analyzed using the method of images. Such semi-infinite and finite
      discrete systems include, for example, waveguide arrays as well as coupled
      resonator optical waveguides. In the linear domain, the diffraction properties of
      one- and two-dimensional bounded array structures are considered in detail. The
      possibility of using the method of images to numerically investigate nonlinear
      semi-infinite lattices is also discussed.

PMID- 16605687
TI  - Modulation instability in nonlinear negative-index material.
AB  - We investigate modulation instability (MI) in negative-index material (NIM) with
      a Kerr nonlinear polarization based on a derived (3+1)-dimensional nonlinear
      Schrodinger equation for ultrashort pulse propagation. By a standard linear
      stability analysis, we obtain the expression for instability gain, which unifies
      the temporal, spatial, and spatiotemporal MI. It is shown that negative
      refraction not only brings some new features to MI, but also makes MI possible in
      ordinary material in which it is otherwise impossible. For example, spatial MI
      can occur in the defocusing regime, while it only occurs in the focusing regime
      in ordinary material. Spatiotemporal MI can appear in NIM in the case of
      anomalous dispersion and defocusing nonlinearity, while it cannot appear in
      ordinary material in the same case. We believe that the difference between the MI
      in NIM and in ordinary material is due to the fact that negative refraction
      reverses the sign of the diffraction term, with the signs of dispersion and
      nonlinearity unchanged. The most notable property of MI in NIM is that it can be
      manipulated by engineering the self-steepening effect by choosing the size of
      split-ring resonator circuit elements. To sum up the MI in ordinary material and
      in NIM, MI may occur for all the combinations of dispersion and nonlinearity.

PMID- 16605688
TI  - q-breathers in Fermi-Pasta-Ulam chains: existence, localization, and stability.
AB  - The Fermi-Pasta-Ulam (FPU) problem consists of the nonequipartition of energy
      among normal modes of a weakly anharmonic atomic chain model. In the harmonic
      limit, each normal mode corresponds to a periodic orbit in phase space and is
      characterized by its wave number q. We continue normal modes from the harmonic
      limit into the FPU parameter regime and obtain persistence of these periodic
      orbits, termed here q-breathers (QB). They are characterized by time periodicity,
      exponential localization in the q-space of normal modes, and linear stability up
      to a size-dependent threshold amplitude. Trajectories computed in the original
      FPU setting are perturbations around these exact QB solutions. The QB concept is
      applicable to other nonlinear lattices as well.

PMID- 16605689
TI  - Multiple scattering: the key to unravel the subwavelength world from the far
      field pattern of a scattered wave.
AB  - For more than a century the possibility of imaging the structure of a medium with
      diffracting wave fields has been limited by the tradeoff between resolution and
      imaging depth. While long wavelengths can penetrate deep into a medium, the
      resolution limit precludes the possibility of observing subwavelength structures.
      Near-field microscopy has recently demonstrated that the resolution limit can be
      overcome by bringing a probing sensor within one wavelength distance from the
      surface to be imaged. This paper extends the scope of near-field microscopy to
      the reconstruction of subwavelength structures from measurements performed in the
      far-field. It is shown that the distortion undergone by a wave field as it
      travels through an inhomogeneous medium and the subsequent generation of local
      evanescent fields encode subwavelength information in the far-field due to
      multiple scattering within the medium. This argument is proved theoretically and
      supported by a limited view experiment performed with elastic waves in which an
      image with a resolution better than a third of the wavelength is achieved.

PMID- 16605690
TI  - Retroreflective effect on a right angle left-handed media prism.
AB  - A different retroreflective effect which parallels that encountered with dihedral
      corner reflectors is found in the scattering response of a penetrable left-handed
      media epsilon= mu= -1 right angle prism. More significantly, no diffraction from
      the vertex is found to exist and hence no field singularity for the right angle
      wedge. Although the results are illustrated with microwaves, the concept finds
      applications in optics, acoustics, elasticity, and other media characterized by
      negative index wave propagation.

PMID- 16605691
TI  - Dynamical models for dissipative localized waves of the complex Ginzburg-Landau
      equation.
AB  - Finite-dimensional dynamical models for solitons of the cubic-quintic complex
      Ginzburg-Landau equation (CGLE) are derived. The models describe the evolution of
      the pulse parameters, such as the maximum amplitude, pulse width, and chirp. A
      clear correspondence between attractors of the finite-dimensional dynamical
      systems and localized waves of the continuous dissipative system is demonstrated.
      It is shown that stationary solitons of the CGLE correspond to fixed points,
      while pulsating solitons are associated with stable limit cycles. The models show
      that a transformation from a stationary soliton to a pulsating soliton is the
      result of a Hopf bifurcation in the reduced dynamical system. The appearance of
      moving fronts (kinks) in the CGLE is related to the loss of stability of the
      limit cycles. Bifurcation boundaries and pulse behavior in the regions between
      the boundaries, for a wide range of system parameters, are found from analysis of
      the reduced dynamical models. We also provide a comparison between various models
      and their correspondence to the exact results.

PMID- 16605692
TI  - Periodic orbits of the ensemble of Sinai-Arnold cat maps and pseudorandom number
      generation.
AB  - We propose methods for constructing high-quality pseudorandom number generators
      (RNGs) based on an ensemble of hyperbolic automorphisms of the unit two
      dimensional torus (Sinai-Arnold map or cat map) while keeping a part of the
      information hidden. The single cat map provides the random properties expected
      from a good RNG and is hence an appropriate building block for an RNG, although
      unnecessary correlations are always present in practice. We show that introducing
      hidden variables and introducing rotation in the RNG output, accompanied with the
      proper initialization, dramatically suppress these correlations. We analyze the
      mechanisms of the single-cat-map correlations analytically and show how to
      diminish them. We generalize the Percival-Vivaldi theory in the case of the
      ensemble of maps, find the period of the proposed RNG analytically, and also
      analyze its properties. We present efficient practical realizations for the RNGs
      and check our predictions numerically. We also test our RNGs using the known
      stringent batteries of statistical tests and find that the statistical properties
      of our best generators are not worse than those of other best modern generators.

PMID- 16605693
TI  - Wang-Landau Monte Carlo simulation of the Blume-Capel model.
AB  - We carry out a study of the two-dimensional Blume-Capel model using the Wang
      Landau Monte Carlo method which estimates the density of states g(E) directly.
      This work validates the applicability of this method to multiparametric systems,
      since only one computer run is needed for all range of macroscopic parameters
      (temperature, anisotropy, etc.). The location of the tricritical point is
      determined as kBTt/J=0.609(3), Dt/J=1.966(2), and is in excellent agreement with
      previous estimates. The free energy and the entropy, which are not directly
      accessible by conventional Monte Carlo simulations, are obtained simply using
      g(E).

PMID- 16605694
TI  - Equation-free dynamic renormalization of a Kardar-Parisi-Zhang-type equation.
AB  - In the context of equation-free computation, we devise and implement a procedure
      for using short-time direct simulations of a Kardar-Parisi-Zhang-(KPZ-) type
      equation to calculate the self-similar solution for its ensemble averaged
      correlation function. The method involves "lifting" from candidate pair
      correlation functions to consistent realization ensembles, short bursts of KPZ
      type evolution, and appropriate rescaling of the resulting averaged pair
      correlation functions. Both the self-similar shapes and their similarity
      exponents are obtained at a computational cost significantly reduced to that
      required to reach saturation in such systems.

PMID- 16605695
TI  - Computation of uniform wave forms using complex rays.
AB  - Complex rays and polynomial phase functions are used to numerically solve the
      Helmholtz equation in a realistic two-dimensional smoothly varying heterogeneous
      velocity model with multiple adjacent cusp caustics. Together these two methods
      allow the determination of global uniformly asymptotic solutions in the presence
      of arbitrarily many caustics. Two algorithms are introduced to this end: a two
      point ray tracing algorithm for complex rays and a perturbation method for
      constructing polynomial phase functions. Model representation in complex space is
      performed via discrete cosine transform analysis. Geometrical and uniformly
      asymptotic solutions are computed for a linear layer test model as well as a
      velocity model from Yucca Mountain.

PMID- 16605696
TI  - Simulation of liquid penetration in paper.
AB  - Capillary penetration of a wetting liquid in a microtomographic image of paper
      board, whose linear dimension was close to the average length of wood fibers, was
      simulated by the lattice-Boltzmann method. In spite of the size of the system not
      being large with respect to the size of structural inhomogeneities in the sample,
      for unidirectional penetration the simulated behavior was described well by that
      of the Lucas-Washburn equation, while for radial penetration a radial capillary
      equation described the behavior. In both cases the average penetration depth of
      the liquid front as a function of time followed a power law over many orders of
      magnitude. Capillary penetration of small droplets of liquid was also simulated
      in the same three-dimensional image of paper. In this case the simulation results
      could be described by a generalized form of the radial-penetration equation.

PMID- 16605697
TI  - Testing and tuning symplectic integrators for the hybrid Monte Carlo algorithm in
      lattice QCD.
AB  - We examine a new second-order integrator recently found by Omelyan et al. The
      integration error of the new integrator measured in the root mean square of the
      energy difference, <DeltaH2>1/2, is about 10 times smaller than that of the
      standard second-order leapfrog (2LF) integrator. As a result, the step size of
      the new integrator can be made about three times larger. Taking into account a
      factor 2 increase in cost, the new integrator is about 50% more efficient than
      the 2LF integrator. Integrating over positions first, then momenta, is slightly
      more advantageous than the reverse. Further parameter tuning is possible. We find
      that the optimal parameter for the new integrator is slightly different from the
      value obtained by Omelyan et al, and depends on the simulation parameters. This
      integrator could also be advantageous for the Trotter-Suzuki decomposition in
      quantum Monte Carlo.

PMID- 16605698
TI  - Constrained surrogate time series with preservation of the mean and variance
      structure.
AB  - A method is presented for generating surrogates that are constrained realizations
      of a time series but which preserve the local mean and variance of the original
      signal. The method is based on the popular iterated amplitude adjusted Fourier
      transform method but makes use of a wavelet transform to constrain behavior in
      the time domain. Using this method it is possible to test for local changes in
      the nonlinear properties of the signal. We present an example for a change in
      Hurst exponent in a time series produced by fractional Brownian motion.

PMID- 16605699
TI  - Parallel solver for the time-dependent linear and nonlinear Schrodinger equation.
AB  - A solution of the time-dependent Schrodinger equation is required in a variety of
      problems in physics and chemistry. These include atoms and molecules in time
      dependent electromagnetic fields, time-dependent approaches to atomic collision
      problems, and describing the behavior of materials subjected to internal and
      external forces. We describe an approach in which the finite-element discrete
      variable representation (FEDVR) is combined with the real-space product (RSP)
      algorithm to generate an efficient and highly accurate method for the solution of
      the time-dependent linear and nonlinear Schrodinger equation. The FEDVR provides
      a highly accurate spatial representation using a minimum number of grid points
      while the RSP algorithm propagates the wave function in operations per time step.
      Parallelization of the method is transparent and is implemented here by
      distributing one or two spatial dimensions across the available processors,
      within the message-passing-interface scheme. The complete formalism and a number
      of three-dimensional examples are given; its high accuracy and efficacy are
      illustrated by a comparison with the usual finite-difference method.

PMID- 16605700
TI  - Role of boundary conditions in dynamic studies of nuclear giant resonances and
      collisions.
AB  - Absorbing boundary conditions are often employed in time-dependent mean-field
      calculations to cope with the problem of emitted particles which would otherwise
      return back onto the system and falsify the dynamical evolution. We scrutinize
      two widely used methods, imaginary potentials and gradual attenuation by a mask
      function. To that end, we consider breathing oscillations of a nucleus computed
      on a radial one-dimensional grid in coordinate space. The most critical test case
      is the computation of resonance spectra in the (linear) domain of small amplitude
      motion. Absorbing bounds turn out to provide a reliable alternative to fully
      fledged continuum random phase approximation (RPA) calculations, although rather
      large absorbing bounds are required to simulate reliably well continuum
      conditions. We also investigate the computation of observables in the nonlinear
      domain. This regime turns out to be less demanding. Smaller absorbing margin
      suffice to achieve the wanted absorption effect.

PMID- 16605701
TI  - Better synchronizability predicted by crossed double cycle.
AB  - In this Brief Report, we propose a network model named crossed double cycles,
      which are completely symmetrical and can be considered as the extensions of
      nearest-neighboring lattices. The synchronizability, measured by eigenratio R,
      can be sharply enhanced by adjusting the only parameter, the crossed length m.
      The eigenratio R is shown very sensitive to the average distance L, and the
      smaller average distance will lead to better synchronizability. Furthermore, we
      find that, in a wide interval, the eigenratio R approximately obeys a power-law
      form as R approximately L(1.5).

PMID- 16605702
TI  - Inhomogeneous substructures hidden in random networks.
AB  - We study the structure of the load-based spanning tree (LST) that carries the
      maximum weight of the Erdos-Renyi (ER) random network. The weight of an edge is
      given by the edge-betweenness centrality, the effective number of shortest paths
      through the edge. We find that the LSTs present very inhomogeneous structures in
      contrast to the homogeneous structures of the original networks. Moreover, it
      turns out that the structure of the LST changes dramatically as the edge density
      of an ER network increases, from scale free with a cutoff, scale free, to a
      starlike topology. These would not be possible if the weights are randomly
      distributed, which implies that topology of the shortest path is correlated in
      spite of the homogeneous topology of the random network.

PMID- 16605703
TI  - Chaos edges of z-logistic maps: connection between the relaxation and sensitivity
      entropic indices.
AB  - Chaos thresholds of the z-logistic maps x(t+1)=1-a|xt|(z) (z>1; t=0,1,2,...) are
      numerically analyzed at accumulation points of cycles 2, 3, and 5 (three
      different cycles 5). We verify that the nonextensive q-generalization of a Pesin
      like identity is preserved through averaging over the entire phase space. More
      precisely, we computationally verify lim(t-->infinity) [formula-see text], where
      the entropy S(q) [formula-see text], the sensitivity to the initial conditions
      xi(triple bond)lim(Deltax(0)-->0)Deltax(t)/Deltax(0), and ln(q)x(triple bond)(x(1
      q-1/(1-q)(ln(1)x=ln x). The entropic index [formula-see text], and the
      coefficient [formula-see text] depend on both z and the cycle. We also study the
      relaxation that occurs if we start with an ensemble of initial conditions
      homogeneously occupying the entire phase space. The associated Lebesgue measure
      asymptotically decreases as 1/t(1/q(rel)-1)(q(rel>1). These results (i)
      illustrate the connection (conjectured by one of us) between sensitivity and
      relaxation entropic indices, namely, [formula-see text], where the positive
      numbers Alpha(n), alpha(n) depend on the cycle; (ii) exhibit an unexpected
      scaling, namely, [formula-see text].

PMID- 16605704
TI  - Driving convection in a fluid layer by a temperature gradient or a heat current.
AB  - Bifurcation properties, stability behavior, dynamics, and the heat transfer of
      convection in a horizontal fluid layer that is driven away from thermal
      equilibrium by imposing a vertical temperature difference are compared with those
      resulting from imposing a heat current. Similarities and differences are
      elucidated. In particular various paradigmatic backwards bifurcating convection
      structures that occur, e.g., in binary fluid mixtures are determined numerically
      for the two different driving mechanisms. Conditions are given under which
      current driven convection is stable when temperature driven convection is
      unstable.

PMID- 16605705
TI  - Frequency response in surface-potential driven electrohydrodynamics.
AB  - Using a Fourier approach we offer a general solution to calculations of slip
      velocity within the circuit description of the electrohydrodynamics in a binary
      electrolyte confined by a plane surface with a modulated surface potential. We
      consider the case with a spatially constant intrinsic surface capacitance where
      the net flow rate is, in general, zero while harmonic rolls as well as time
      averaged vortexlike components may exist depending on the spatial symmetry and
      extension of the surface potential. In general, the system displays a resonance
      behavior at a frequency corresponding to the inverse time of the system.
      Different surface potentials share the common feature that the resonance
      frequency is inversely proportional to the characteristic length scale of the
      surface potential. For the asymptotic frequency dependence above resonance we
      find a omega(-2) power law for surface potentials with either an even or an odd
      symmetry. Below resonance we also find a power law omega(alpha) with alpha being
      positive and dependent of the properties of the surface potential. Comparing a
      tanh potential and a sech potential we qualitatively find the same slip velocity,
      but for the below-resonance frequency response the two potentials display
      different power-law asymptotics with alpha=1 and alpha approximately 2,
      respectively.

PMID- 16605706
TI  - Ultrashort solitons and kinetic effects in nonlinear metamaterials.
AB  - We present a stability analysis of a modified nonlinear Schrodinger equation
      describing the propagation of ultrashort pulses in negative refractive index
      media. Moreover, using methods of quantum statistics, we derive a kinetic
      equation for the pulses, making it possible to analyze and describe partial
      coherence in metamaterials. It is shown that a unique short pulse soliton, which
      is found analytically, can propagate in the medium.

PMID- 16605707
TI  - Thermostat with a local heat-bath coupling for exact energy conservation in
      dissipative particle dynamics.
AB  - We present a Markov process which models particle hydrodynamics with conservation
      of the first three momenta. This is achieved by extending the [Peters, Europhys.
      Lett. 66, 311 (2004)] and [Lowe, Europhys. Lett. 47, 145 (1999)] method to
      incorporate energy conservation. The equivalence of the energy conserving Peters
      method and dissipative particle dynamics with energy conservation (DPDE) in the
      limit of a vanishing time step is shown. Simple numerical experiments clearly
      demonstrate the applicability of the methods. This overcomes current limitations
      of DPDE in the study of complex fluids in the (N,V,E) ensemble.

PMID- 16605708
TI  - Comment on "Periodic phase synchronization in coupled chaotic oscillators".
AB  - Kye [Phys. Rev. E 68, 025201 (2003)] have recently claimed that, before the onset
      of chaotic phase synchronization in coupled phase coherent oscillators, there
      exists a temporally coherent state called periodic phase synchronization (PPS).
      Here we give evidence that some of their numerical calculations are flawed, while
      we provide theoretical arguments that indicate that PPS is not to be expected
      generically in this type of systems.

PMID- 16605710
TI  - Poisson transition rates from time-domain measurements with a finite bandwidth.
AB  - In time-domain measurements of a Poisson two-level system, the observed
      transition rates are always smaller than those of the actual system, a general
      consequence of a finite measurement bandwidth in an experiment. This
      underestimation of the rates is significant even when the measurement and
      detection apparatus are 10 times faster than the process under study. We derive
      here a quantitative form for this correction, using a straightforward state
      transition model that includes the detection apparatus, and provide a method for
      determining a system's actual transition rates from bandwidth-limited
      measurements. We support our results with computer simulations and experimental
      data from time-domain measurements of quasiparticle tunneling in a single-Cooper
      pair transistor.

PMID- 16605711
TI  - Pseudopotential analog for zero-range photoassociation and Feshbach resonance.
AB  - A zero-range approach to atom-molecule coupling is developed in analogy to the
      Fermi-Huang pseudopotential approach to collisions. It is shown by explicit
      comparison to an exactly solvable finite-range model that replacing the molecular
      bound-state wave function with a regularized delta function can reproduce the
      exact scattering amplitude in the long-wavelength limit. Using this approach, we
      find an analytical solution to the two-channel Feshbach resonance problem for two
      atoms in a spherical harmonic trap, highlighting the strong dependence of the
      effective scattering length and bare-molecule population on the atom-molecule
      coupling strength.

PMID- 16605712
TI  - Lateral Casimir force beyond the proximity-force approximation.
AB  - We argue that the appropriate variable to study a nontrivial geometry dependence
      of the Casimir force is the lateral component of the Casimir force, which we
      evaluate between two corrugated metallic plates outside the validity of the
      proximity-force approximation. The metallic plates are described by the plasma
      model, with arbitrary values for the plasma wavelength, the plate separation, and
      the corrugation period, the corrugation amplitude remaining the smallest length
      scale. Our analysis shows that in realistic experimental situations the proximity
      force approximation overestimates the force by up to 30%.

PMID- 16605713
TI  - Quantum interference enforced by time-energy complementarity.
AB  - The interplay of the concepts of complementarity and interference in the time
      energy domain are studied. In particular, we theoretically investigate the
      fluorescence light from a J = 1/2 to J= 1/2 transition that is driven by a
      monochromatic laser field. We find that the spectrum of resonance fluorescence
      exhibits a signature of vacuum-mediated interference effects, whereas the total
      intensity is not affected by interference. We demonstrate that this result is a
      consequence of the principle of complementarity, applied to time and energy.
      Since the considered level scheme can be found, e.g., in (198)Hg(+) ions, our
      model system turns out to be an ideal candidate to provide evidence for as yet
      experimentally unconfirmed vacuum-induced atomic coherences.

PMID- 16605714
TI  - Motion of an electron from a point source in parallel electric and magnetic
      fields.
AB  - Negative ions undergoing near-threshold photodetachment in a weak laser field
      provide an almost pointlike, isotropic source of low-energy electrons. External
      fields exert forces on the emitted coherent electron wave and direct its motion.
      Here, we examine the spatial distribution of photodetached electrons in uniform,
      parallel electric and magnetic fields. The interplay of the electric and magnetic
      forces leads to a surprising intricate shape of the refracted electron wave, and
      multiple interfering trajectories generate complex fringe patterns in the matter
      wave. The exact quantum solution is best understood in terms of the classical
      electron motion.

PMID- 16605715
TI  - Preserving quantum states using inverting pulses: a super-Zeno effect.
AB  - We construct an algorithm for suppressing the transitions of a quantum mechanical
      system, initially prepared in a subspace P of the full Hilbert space of the
      system, to outside this subspace by subjecting it to a sequence of unequally
      spaced short-duration pulses. Each pulse multiplies the amplitude of the vectors
      in the subspace by -1. The number of pulses required by the algorithm to limit
      the leakage probability to epsilon in time increases as T exp[square root
      log(T(2)/epsilon)], compared to T(2)epsilon(-1) in the standard quantum Zeno
      effect.

PMID- 16605716
TI  - Charge-fluctuation-induced dephasing of exchange-coupled spin qubits.
AB  - Exchange-coupled spin qubits in semiconductor nanostructures are shown to be
      vulnerable to dephasing caused by charge noise invariably present in the
      semiconductor environment. This decoherence of exchange gate by environmental
      charge fluctuations arises from the fundamental Coulombic nature of the
      Heisenberg coupling and presents a serious challenge to the scalability of the
      widely studied exchange gate solid state spin quantum computer architectures. We
      estimate dephasing times for coupled spin qubits in a wide range (from 1 ns up to
      >1 micros) depending on the exchange coupling strength and its sensitivity to
      charge fluctuations.

PMID- 16605717
TI  - Entanglement persistency of multiphoton entangled states.
AB  - We experimentally demonstrate the entanglement persistency when losing photons in
      three- and four-photon polarization-entangled states. The entanglement properties
      of the mixed states obtained from multiphoton spontaneous parametric down
      conversion are studied via witness and positive partial transpose approaches.
      Together with a quantification of the bipartite entanglement such analysis
      enables intuitive understanding of novel multiparty quantum communication
      protocols.

PMID- 16605718
TI  - Entanglement entropy of fermions in any dimension and the Widom conjecture.
AB  - We show that entanglement entropy of free fermions scales faster than area law,
      as opposed to the scaling L(d-1) for the harmonic lattice, for example. We also
      suggest and provide evidence in support of an explicit formula for the
      entanglement entropy of free fermions in any dimension d, S approximately
      c(deltagamma, deltaomega)L(d-1) logL as the size of a subsystem L-->infinity,
      where deltagamma is the Fermi surface and is the boundary of the region in real
      space. The expression for the constant c(deltagamma, deltaomega) is based on a
      conjecture due to Widom. We prove that a similar expression holds for the
      particle number fluctuations and use it to prove a two sided estimate on the
      entropy S.

PMID- 16605719
TI  - Normal heat conduction in a chain with a weak interparticle anharmonic potential.
AB  - We analytically study heat conduction in a chain with an interparticle
      interaction V(x)= lambda[1-cos(x)] and harmonic on-site potential. We start with
      each site of the system connected to a Langevin heat bath, and investigate the
      case of small coupling for the interior sites in order to understand the behavior
      of the system with thermal reservoirs at the boundaries only. We study, in a
      perturbative analysis, the heat current in the steady state of the one
      dimensional system with a weak interparticle potential. We obtain an expression
      for the thermal conductivity, compare the low and high temperature regimes, and
      show that, as we turn off the couplings with the interior heat baths, there is a
      "phase transition": Fourier's law holds only at high temperatures.

PMID- 16605720
TI  - Optimal estimates of free energies from multistate nonequilibrium work data.
AB  - We derive the optimal estimates of the free energies of an arbitrary number of
      thermodynamic states from nonequilibrium work measurements; the work data are
      collected from forward and reverse switching processes and obey a fluctuation
      theorem. The maximum likelihood formulation properly reweights all pathways
      contributing to a free energy difference and is directly applicable to
      simulations and experiments. We demonstrate dramatic gains in efficiency by
      combining the analysis with parallel tempering simulations for alchemical
      mutations of model amino acids.

PMID- 16605721
TI  - Boundary effects in the critical scaling of entanglement entropy in 1D systems.
AB  - We present exact diagonalization and density matrix renormalization group results
      for the entanglement entropy of critical spin-1/2 XXZ chains. We find that open
      boundary conditions induce an alternating term in both the energy density and the
      entanglement entropy which are approximately proportional, decaying away from the
      boundary with a power law. The power varies with anisotropy along the critical
      line and is corrected by a logarithmic factor, which we calculate analytically,
      at the isotropic point. A heuristic resonating valence bond explanation is
      suggested.

PMID- 16605722
TI  - Angular-momentum--mass inequality for axisymmetric black holes.
AB  - The inequality square root J <or=m is proved for vacuum, asymptotically flat,
      maximal, and axisymmetric data close to extreme Kerr data. The physical
      significance of this inequality and its relation to the standard picture of the
      gravitational collapse are discussed.

PMID- 16605723
TI  - Measurement of the K0 charge radius and a CP-violating asymmetry and a search for
      CP-violating E1 direct photon emission in the rare decay KL--> pi+ pi- e+ e-.
AB  - Using the complete KTeV data set of 5,241 candidate K(L)--> pi(+) pi(-) e(+) e(-)
      decays (including an estimated background of 204 +/- 14 events), we have measured
      the coupling g(CR)= 0.163 +/- 0.0149(stat) +/- 0.023(syst) of the CP conserving
      charge radius process and from it determined a K(0) charge radius of <r(2)(K(0))>
      = [-0.077 +/- 0.007(stat) +/- 0.011(syst)]fm(2). We have determined a first
      experimental upper limit of 0.04 (90% C.L.) /g(e1)/ / /g(M1)/ of the couplings
      for the E1 and M1 direct photon emission processes. We also report the
      measurement of /g(M1)/ including a vector form factor /g(M1)/(1 +
      (a(1)/a(2))/((M(2)(p)-(M(2)(k))= 2M(K)E(gamma*)), where vector /g(M1)/= 1.11+/-
      0.12(stat) +/- 0.08(syst) and a(1)/a(2) = [-0.744 +/- 0.027(stat) +/-
      0.032(syst)] GeV(2)/c(2). Finally, a CP-violating asymmetry of [13.6 +/-
      1.4(stat) +/- 1.5(syst)]% in the CP and T odd angle phi between the decay planes
      of the e(+) e(-) and pi(+) pi(-) pairs in the K(L) center of mass is reported.

PMID- 16605725
TI  - Anticharmed pentaquark from B decays.
AB  - We explore the possibility of observing the anticharmed pentaquark state from the
      theta(c)npi(+) decay of B mesons produced in B-factory experiments. We first show
      that the observed branching ratio of the B(+) to lambda(-)(c)p pi(+), as well as
      its open histograms, can be remarkably well explained by assuming that the decay
      proceeds first through the pi(+) D(0) (or D(*0)) decay, and then through the
      subsequent decay of the virtual D(0) or D(*0) mesons to lambda(-)(c)p. We then
      note that the theta(c)can be similarly produced when the virtual D(0) or D(*0)
      decay into an antinucleon and a theta(c). Combining the present theoretical
      estimates for the ratio g(DNlambda(c))/g(DNtheta(c)) approximately 13 and
      g(D*Ntheta(c)) approximately 1/3g(DNtheta(c)), we find that the anticharmed
      pentaquark theta(c), which was predicted to be bound by several model
      calculations, can be produced via B(+)--> theta(c)npi(+), and be observed from
      the B-factory experiments through the weak decay of theta(c)--> pK(+) pi(-) pi(
      ).

PMID- 16605724
TI  - Search for the invisible decay of neutrons with KamLAND.
AB  - The Kamioka Liquid scintillator Anti-Neutrino Detector is used in a search for
      single neutron or two-neutron intranuclear disappearance that would produce holes
      in the -shell energy level of (12)C nuclei. Such holes could be created as a
      result of nucleon decay into invisible modes (inv), e.g., n--> 3v or nn--> 2v.
      The deexcitation of the corresponding daughter nucleus results in a sequence of
      space and time-correlated events observable in the liquid scintillator detector.
      We report on new limits for one- and two-neutron disappearance: tau(n--> inv) >
      5.8 x 10(29) years and tau (nn--> inv) > 1.4 x 10(30) years at 90% C.L. These
      results represent an improvement of factors of approximately 3 and >10(4) and
      over previous experiments.

PMID- 16605727
TI  - Nuclear magnetic moment of the 57Cu ground state.
AB  - The nuclear magnetic moment of the ground state of (57)Cu(Iota(pi) = 3/2(-),
      T(1/2) = 196.3 ms) has been measured to be /mu((57)Cu)/ = (2.00 +/- 0.05)mu(N)
      using the beta-NMR technique. Together with the known magnetic moment of the
      mirror partner (57)Ni, the spin expectation value was extracted as
      <Sigmasigma(z)> = -0.078 +/- 0.13. This is the heaviest isospin mirror T = 1/2
      pair above the (40)Ca region for which both ground state magnetic moments have
      been determined. The discrepancy between the present results and shell-model
      calculations in the full f p shell giving mu((57)Cu) approximately 2.4mu(N) and
      <Sigmasigma(z)> approximately 0.5 implies significant shell breaking at (56)Ni
      with the neutron number N = 28.

PMID- 16605728
TI  - Observation of three-dimensional long-range order in small ion coulomb crystals
      in an rf trap.
AB  - Three-dimensional long-range ordered structures in smaller and near-spherically
      symmetric Coulomb crystals of (40)Ca(+) ions confined in a linear rf Paul trap
      have been observed when the number of ions exceeds approximately 1,000 ions. This
      result is unexpected from ground state molecular dynamics (MD) simulations, but
      found to be in agreement with MD simulations of metastable ion configurations.
      Previously, three-dimensional long-range ordered structures have only been
      reported in Penning traps in systems of approximately 50,000 ions or more.

PMID- 16605729
TI  - Quantum state measurement using coherent transients.
AB  - We present the principle and experimental demonstration of time resolved quantum
      state holography. The quantum state of an excited state interacting with an
      ultrashort chirped laser pulse is measured during this interaction. This has been
      obtained by manipulating coherent transients created by the interaction of
      femtosecond shaped pulses and rubidium atoms.

PMID- 16605730
TI  - Hyperpolarizability effects in a Sr optical lattice clock.
AB  - We report the observation of a higher-order frequency shift due to the trapping
      field in a (87)Sr optical lattice clock. We show that, at the magic wavelength of
      the lattice, where the first-order term cancels, the higher-order shift will not
      constitute a limitation to the fractional accuracy of the clock at a level of 10(
      18). This result is achieved by operating the clock at very high trapping
      intensity up to 400 kW/cm(2) and by a specific study of the effect of the two two
      photon transitions near the magic wavelength.

PMID- 16605731
TI  - Detecting correlation functions of ultracold atoms through fourier sampling of
      time-of-flight images.
AB  - We propose a detection method for ultracold atoms which allows reconstruction of
      the full one-particle and two-particle correlation functions from the
      measurements. The method is based on Fourier sampling of the time-of-flight
      images through two consecutive impulsive Raman pulses. For applications of this
      method, we discuss a few examples, including detection of phase separation
      between superfluid and Mott insulators, various types of spin or superfluid
      orders, entanglement, exotic or fluctuating orders.

PMID- 16605732
TI  - Experimental and quantum dynamical study on an asymmetric insertion reaction:
      state-to-state dynamics of O(1D) + HD(1Sigmag+, v' = 0, j' = 0)-->OH(Pi, v", N")
      + D(2S).
AB  - Quantum-state-resolved differential cross sections of the O((1)D) + HD --> OH + D
      reaction at the collision energy of 7.11 kJ/mol has been determined
      experimentally and theoretically. The results of the time-dependent wave-packet
      calculations are overall in good agreement with the crossed beam scattering data,
      providing a benchmark example of an asymmetric insertion reaction at the state-to
      state scattering level. The good agreement between experiment and theory suggests
      that the underlying ground potential energy surface is generally correct and that
      the nonadiabatic effect involving the electronic excited pathway is apparently
      small in this system.

PMID- 16605733
TI  - Switching control of spontaneous emission by polarized atoms in two-dimensional
      photonic crystals.
AB  - We calculate the lifetime distribution function of an assembly of polarized atoms
      in two-dimensional (2D) photonic crystals (PCs) at different polarization
      orientations of atomic dipole moments. We reveal a switching effect of atomic
      spontaneous emission (SE) and find a significant change of atomic lifetime, up to
      a factor of 33, by tuning the polarized orientation of the atoms. These
      observations suggest that the tuning of the polarized orientation of atoms
      provides a new way for the effective control of atomic SE processes in 2D PCs.

PMID- 16605734
TI  - Dynamical multistability induced by radiation pressure in high-finesse
      micromechanical optical cavities.
AB  - We analyze the nonlinear dynamics of a high-finesse optical cavity in which one
      mirror is mounted on a flexible mechanical element. We find that this system is
      governed by an array of dynamical attractors, which arise from phase locking
      between the mechanical oscillations of the mirror and the ringing of the light
      intensity in the cavity. We develop an analytical theory to map out the diagram
      of attractors in parameter space, derive the slow amplitude dynamics of the
      system, including thermal fluctuations, and suggest a scheme for exploiting the
      dynamical multistability in the measurement of small displacements.

PMID- 16605735
TI  - Spontaneous emission suppression via quantum path interference in coupled
      microcavities.
AB  - We examine theoretically the spontaneous emission rate in optical microstructures
      with cavity resonances that overlap in both position and frequency. Using
      projection techniques, we show that the spontaneous emission in such structures
      can be accurately described by the direct emission and quantum path interference
      of emission into a few discrete resonant modes, even though the exact infinite
      dimensional problem involves a coupling to the continuum of radiation states.
      Moreover, we obtain an efficient numerical time-domain method for determining the
      spontaneous emission rate that incorporates these effects, including the
      suppression of spontaneous emission into some modes.

PMID- 16605736
TI  - Control of electrical alternans in canine cardiac purkinje fibers.
AB  - Alternation in the duration of consecutive cardiac action potentials (electrical
      alternans) may precipitate conduction block and the onset of arrhythmias.
      Consequently, suppression of alternans using properly timed premature stimuli may
      be antiarrhythmic. To determine the extent to which alternans control can be
      achieved in cardiac tissue, isolated canine Purkinje fibers were paced from one
      end using a feedback control method. Spatially uniform control of alternans was
      possible when alternans amplitude was small. However, control became attenuated
      spatially as alternans amplitude increased. The amplitude variation along the
      cable was well described by a theoretically expected standing wave profile that
      corresponds to the first quantized mode of the one-dimensional Helmholtz
      equation. These results confirm the wavelike nature of alternans and may have
      important implications for their control using electrical stimuli.

PMID- 16605737
TI  - Time reversal of ultrasound through a phononic crystal.
AB  - In this Letter, we experimentally investigate time reversal focusing through a
      phononic crystal consisting of a periodic square arrangement of steel rods in
      water. An acoustic pulse is transmitted through the medium, received at a
      transducer array, time reversed and backpropagated. Both spatial focusing and
      time compression are studied and compared with those obtained through an
      equivalent disordered medium. With the phononic crystal, we do not observe the
      "hyperfocusing effect" that is typical of time reversal through disordered
      samples.

PMID- 16605738
TI  - Self-propelled particles with soft-core interactions: patterns, stability, and
      collapse.
AB  - Understanding collective properties of driven particle systems is significant for
      naturally occurring aggregates and because the knowledge gained can be used as
      building blocks for the design of artificial ones. We model self-propelling
      biological or artificial individuals interacting through pairwise attractive and
      repulsive forces. For the first time, we are able to predict stability and
      morphology of organization starting from the shape of the two-body interaction.
      We present a coherent theory, based on fundamental statistical mechanics, for all
      possible phases of collective motion.

PMID- 16605739
TI  - Rayleigh-Taylor instability for immiscible fluids of arbitrary viscosities: a
      magnetic levitation investigation and theoretical model.
AB  - A magnetic field gradient was used to draw down a low density paramagnetic fluid
      below a more dense fluid in a Hele-Shaw cell. On turning off the field a Rayleigh
      Taylor instability was observed in situ, and the growth of the most unstable wave
      vector was measured versus time. A theory for the instability that permits
      different viscosities for two immiscible fluids was developed, and good agreement
      was found with the experimental results. The technique of magnetic levitation
      promises to broaden significantly the accessible parameter space of gravitational
      interfacial instability experiments.

PMID- 16605740
TI  - Nonlinear dynamics of an interface between shear bands.
AB  - We study numerically the nonlinear dynamics of a shear banding interface in two
      dimensional planar shear flow, within the nonlocal Johnson-Segalman model.
      Consistent with a recent linear stability analysis, we find that an initially
      flat interface is unstable with respect to small undulations for a sufficiently
      small ratio of the interfacial width l to cell length L(x). The instability
      saturates in finite amplitude interfacial fluctuations. For decreasing l/L(x)
      these undergo a nonequilibrium transition from simple traveling interfacial waves
      with constant average wall stress, to periodically rippling waves with a periodic
      stress response. When multiple shear bands are present we find erratic
      interfacial dynamics and a stress response suggesting low dimensional chaos.

PMID- 16605726
TI  - Measurement of the dipion mass spectrum in decays.
AB  - We measure the dipion mass spectrum in X(3872)--> J/psipi(+) pi(-) decays using
      360 pb(-1) of pp collisions at square root s= 1.96 TeV collected with the CDF II
      detector. The spectrum is fit with predictions for odd C-parity ((3)S(1),
      (1)P(1), and (3)D(J)) charmonia decaying to J/psipi(+) pi(-), as well as even C
      parity states in which the pions are from rho(0) decay. The latter case also
      encompasses exotic interpretations, such as a D(0)D(*0) molecule. Only the
      (3)S(1) and J/psirho hypotheses are compatible with our data. Since (3)S(1) is
      untenable on other grounds, decay via J/psirho is favored, which implies C= +1
      for the X(3872). Models for J/psi - rho different angular momenta L are
      considered. Flexibility in the models, especially the introduction of rho - omega
      interference, enables good descriptions of our data for both L = 0 and 1.

PMID- 16605741
TI  - Laser ion-acceleration scaling laws seen in multiparametric particle-in-cell
      simulations.
AB  - The ion acceleration driven by a laser pulse at intensity I= 10(20)-10(22)
      W/cm(2) x (microm/lambda)(2) from a double layer target is investigated with
      multiparametric particle-in-cell simulations. For targets with a wide range of
      thickness l and density n(e), at a given intensity, the highest ion energy gain
      occurs at certain electron areal density of the target sigma = n(e)l, which is
      proportional to the square root of intensity. In the case of thin targets and
      optimal laser pulse duration, the ion maximum energy scales as the square root of
      the laser pulse power. When the radiation pressure of the laser field becomes
      dominant, the ion maximum energy becomes proportional to the laser pulse energy.

PMID- 16605743
TI  - Observation of collective modes of ultracold plasmas.
AB  - Applying a radio-frequency electric field to an expanding ultracold neutral
      plasma leads to the observation of as many as six peaks in the emission of
      electrons from the plasma. These are identified as collective modes of the plasma
      and are in qualitative agreement with a model of Tonks-Dattner resonances,
      electron sound waves propagating in a finite-sized, inhomogeneous plasma. Such
      modes may provide an accurate method to determine the time-dependent electron
      temperature.

PMID- 16605742
TI  - Space-charge effects in the current-filamentation or Weibel instability.
AB  - We consider how an unmagnetized plasma responds to an incoming flux of energetic
      electrons. We assume a return current is present and allow for the incoming
      electrons to have a different transverse temperature than the return current. To
      analyze this configuration we present a nonrelativistic theory of the current
      filamentation or Weibel instability for rigorously current-neutral and
      nonseparable distribution functions, f(0)(p(x), p(y), p(z)) is not equal to
      f(x)(p(x))f(y)(p(y))f(z)(p(z)). We find that such distribution functions lead to
      lower growth rates because of space-charge forces that arise when the forward
      going electrons pinch to a lesser degree than the colder, backward-flowing
      electrons. We verify the growth rate, range of unstable wave numbers, and the
      formation of the density filaments using particle-in-cell simulations.

PMID- 16605744
TI  - Generation of quasimonoenergetic electron bunches with 80-fs laser pulses.
AB  - Highly collimated, quasimonoenergetic multi-MeV electron bunches were generated
      by the interaction of tightly focused, 80-fs laser pulses in a high-pressure gas
      jet. These monoenergetic bunches are characteristic of wakefield acceleration in
      the highly nonlinear wave breaking regime, which was previously thought to be
      accessible only by much shorter laser pulses in thinner plasmas. In our
      experiment, the initially long laser pulse was modified in underdense plasma to
      match the necessary conditions. This picture is confirmed by semianalytical
      scaling laws and 3D particle-in-cell simulations. Our results show that laser
      plasma interaction can drive itself towards this type of laser wakefield
      acceleration even if the initial laser and plasma parameters are outside the
      required regime.

PMID- 16605745
TI  - Self-organized-criticality model consistent with statistical properties of edge
      turbulence in a fusion plasma.
AB  - The statistical properties of the intermittent signal generated by a recent model
      for self-organized criticality are examined. A successful comparison is made with
      previously published results of the equivalent quantities measured in the
      electrostatic turbulence at the edge of a fusion plasma. This result
      reestablishes self-organized criticality as a potential paradigm for transport in
      magnetic fusion devices, overriding shortcomings pointed out in earlier works [E.
      Spada, Phys. Rev. Lett. 86, 3032 (2001)10.1103/PhysRevLett.86.3032; V. Antoni,
      Phys. Rev. Lett. 87, 045001 (2001)10.1103/PhysRevLett.87.045001].

PMID- 16605746
TI  - Multitude of core-localized shear Alfven waves in a high-temperature fusion
      plasma.
AB  - Evidence is presented for a multitude of discrete frequency Alfven waves in the
      core of magnetically confined high-temperature fusion plasmas. Multiple
      diagnostic instruments confirm wave excitation over a wide spatial range from the
      device size at the longest wavelengths down to the thermal ion Larmor radius. At
      the shortest scales, the poloidal wavelengths are comparable to the scale length
      of electrostatic drift wave turbulence. Theoretical analysis confirms a dominant
      interaction of the modes with particles in the thermal ion distribution traveling
      well below the Alfven velocity.

PMID- 16605747
TI  - Analysis of bifurcation phenomena in the electron internal transport barrier in
      the large helical device.
AB  - The electron internal transport barrier (eITB) formation in the Large Helical
      Device (LHD) is studied with the transport code TOTAL and a GyroBohm-like model.
      The reduction of anomalous transport by the E x B shear has been introduced by
      means of the factor [1 + (tauomega(ExB))(gamma)](-1). Simulation results show a
      clear critical transition between plasma regimes with rather flat electron
      temperature profiles (non-) to a steeped one (with eITB) when average density is
      low enough. With the aim of studying the eITB formation as a phase transition
      phenomenon, the electron average density is taken as the control parameter and
      the E x B shearing rate as the order parameter. Results show how the eITB
      formation in LHD is compatible with a continuum phase transition with critical
      exponent beta = 0.40.

PMID- 16605748
TI  - Three-dimensional magnetic structures generated by the development of the
      filamentation (Weibel) instability in the relativistic regime.
AB  - We present three-dimensional, fully relativistic, fluid simulations of the
      dynamics of inhomogeneous counter streaming beams with the aim of understanding
      the magnetic structures that can be expected to form as a consequence of the
      development of the so-called Weibel instability. Ringlike structures in the
      transverse direction are generated as a consequence of the development of a
      spatially resonant mode. We describe the structures generated by beams of equal
      initial density and velocity and by a fast, less dense beam compensated by a
      slower, denser beam. We consider these two cases as schematic models of a laser
      produced beam propagating in a plasma with nearly equal density and in a plasma
      much denser than the injected beam.

PMID- 16605749
TI  - Evolution of discharge structure in capacitive radio-frequency atmospheric
      microplasmas.
AB  - Conventional radio-frequency (rf) nonthermal atmospheric plasmas are generated in
      a millimeter gap. In this Letter, we present a self-consistent numerical study of
      rf atmospheric microplasmas in a submillimeter gap comparable to their sheath
      thickness. It is shown that the narrow electrode gap deforms the discharge
      structure, ultimately removing the bulk-plasma region and disabling electron
      trapping. Significantly, these properties permit rf atmospheric microplasmas to
      operate at very high current densities thus simultaneously achieving higher
      stability and greater chemical reactivity.

PMID- 16605750
TI  - Superdiffusion and viscoelastic vortex flows in a two-dimensional complex plasma.
AB  - Viscoelastic vortical fluid motion in a strongly coupled particle system has been
      observed experimentally. Optical tracking of particle motion in a complex plasma
      monolayer reveals high grain mobility and large scale vortex flows coexistent
      with partial preservation of the global hexagonal lattice structure. The
      transport of particles is superdiffusive and ascribed to Levy statistics on short
      time scales and to memory effects on the longer scales influenced by cooperative
      motion. At these longer time scales, the transport is governed by vortex flows
      covering a wide spectrum of temporal and spatial scales.

PMID- 16605751
TI  - Superglass phase of 4He.
AB  - We study different solid phases of 4He, by means of path integral Monte Carlo
      simulations based on a recently developed worm algorithm. Our study includes
      simulations that start off from a high- gas phase, which is then "quenched" down
      to T = 0.2 K. The low-T properties of the system crucially depend on the initial
      state. While an ideal hcp crystal is a clear-cut insulator, the disordered system
      freezes into a superglass, i.e., a metastable amorphous solid featuring off
      diagonal long-range order and superfluidity.

PMID- 16605752
TI  - Off-diagonal long-range order in solid 4He.
AB  - Measurements of the moment of inertia by Kim and Chan have found that solid (4)He
      acts like a supersolid at low temperatures. To understand the order in solid
      4(He), we have used path integral Monte Carlo simulations to calculate the off
      diagonal long-range order (ODLRO) [equivalent to Bose-Einstein condensation
      (BEC)]. We do not find ODLRO in a defect-free hcp crystal of (4)He at the melting
      density. We discuss these results in relation to proposed quantum solid trial
      functions. We conclude that the solid (4)He wave function has correlations which
      suppress both vacancies and BEC.

PMID- 16605753
TI  - Excitations in correlated superfluids near a continuous transition into a
      supersolid.
AB  - We study a superfluid on a lattice close to a transition into a supersolid phase
      and show that a uniform superflow in the homogeneous superfluid can drive the
      roton gap to zero. This leads to supersolid order around the vortex core in the
      superfluid, with the size of the modulated pattern around the core being related
      to the bulk superfluid density and roton gap. We also study the electronic
      tunneling density of states for a uniform superconductor near a phase transition
      into a supersolid phase. Implications are considered for strongly correlated
      superconductors.

PMID- 16605754
TI  - Pressure-driven flow of solid helium.
AB  - The recent torsional oscillator results of Kim and Chan show an anomalous mass
      decoupling, interpreted by the authors as a supersolid phase transition, in solid
      (4)He. We have used a piezoelectrically driven diaphragm to study the flow of
      solid helium through an array of capillaries. Our measurements showed no
      indication of low temperature flow, placing stringent restrictions on supersolid
      flow in response to a pressure difference. The average flow speed at low
      temperatures was less than 1.2 x 10(-14) m/s, corresponding to a supersolid
      velocity at least 7 orders of magnitude smaller than the critical velocities
      inferred from the torsional oscillator measurements.

PMID- 16605755
TI  - Accurate equation of state of AlPdMn up to 35 GPa and pressure effect on the
      frozen-in phason strain.
AB  - Angle-dispersive monochromatic x-ray diffraction spectra from a perfect single
      grain AlPdMn quasicrystal have been obtained under hydrostatic pressure in a
      diamond anvil cell up to 35 GPa. More than 50 Bragg peaks with sharpness
      comparable to that at ambient conditions were observed up to the maximum
      pressure, indexed and used to measure the hypercubic 6D lattice parameter,
      providing the most accurate determination of the equation of state in this
      pressure range to date. Within the instrumental resolution, the absence of
      broadening of the diffraction peaks indicates the absence of structural
      transition and/or unusual configurational entropy change expected from previous
      studies through pressure-induced amorphization or phason defects.

PMID- 16605756
TI  - Hyper-Raman scattering from vitreous boron oxide: coherent enhancement of the
      boson peak.
AB  - Hyper-Raman scattering spectra of vitreous B(2)O(3) are compared to Raman
      scattering ones. Particular attention is given to the low-frequency boson peak
      which relates to out-of-plane rigid librations of planar structural units, mostly
      boroxols. While the Raman strength can be accounted for by the motions of single
      units, the hyper-Raman signal exhibits a unequaled enhancement due to coherent
      librations of several boroxols. This important distinction is explained by the
      different symmetry properties of the polarizability and hyperpolarizability
      tensors of the structural units.

PMID- 16605757
TI  - Softening caused by profuse shear banding in a bulk metallic glass.
AB  - By controlling the specimen aspect ratio and strain rate, compressive strains as
      high as 80% were obtained in an otherwise brittle metallic glass. Physical and
      mechanical properties were measured after deformation, and a systematic strain
      induced softening was observed which contrasts sharply with the hardening
      typically observed in crystalline metals. If the deformed glass is treated as a
      composite of hard amorphous grains surrounded by soft shear-band boundaries,
      analogous to nanocrystalline materials that exhibit inverse Hall-Petch behavior,
      the correct functional form for the dependence of hardness on shear-band spacing
      is obtained. Deformation-induced softening leads naturally to shear localization
      and brittle fracture.

PMID- 16605758
TI  - Transition to a virtually incompressible oxide phase at a shock pressure of 120
      GPa (1.2 Mbar): Gd3Ga5O12.
AB  - Cubic, single-crystal, transparent Gd(3)Ga(5)O(12) has a density of 7.10 g/cm(3),
      a Hugoniot elastic limit of 30 GPa, and undergoes a continuous phase transition
      from 65 GPa to a quasi-incompressible (QI) phase at 120 GPa. Only diamond has a
      larger Hugoniot elastic limit. The QI phase of is more incompressible than
      diamond from 170 to 260 GPa. Electrical conductivity measurements indicate the QI
      phase has a band gap of 3.1 eV. Gd(3)Ga(5)O(12) can be used to obtain
      substantially higher pressures and lower temperatures in metallic fluid hydrogen
      than was achieved previously by shock reverberation between Al(2)O(3) disks.

PMID- 16605759
TI  - Atomic and electronic structures of carbon nanotubes on Si(001) stepped surfaces.
AB  - We report first-principles total-energy calculations that provide energetics and
      electronic structures of adsorbed carbon nanotubes (CNTs) on stepped Si(001)
      surfaces. We find that adsorption energies strongly depend on the directions of
      CNTs, and that there are several metastable adsorption sites both on terraces and
      near step edges. We also find that the electronic structure of adsorbed metallic
      CNTs becomes semiconducting or remains metallic, depending on the adsorption
      site. Charge redistribution upon adsorption is prominent mainly at the CNT
      surface interface.

PMID- 16605760
TI  - Two scenarios for colloidal phase transitions.
AB  - A two-dimensional assembly of charged colloidal particles induced by an
      alternating electric field was studied in real space by means of digital video
      microscopy. Phase transitions occur from a highly ordered colloidal monolayer to
      an isotropic suspension by changing the field strength or frequency (in the
      appropriate range). In particular, it is found that the strength-dependent phase
      transition is an infinite-order phase transition, in contrast with the frequency
      dependent phase transition, which is a second-order phase transition.

PMID- 16605761
TI  - Pressure-induced phase transitions in the Cd-Yb periodic approximant to a
      quasicrystal.
AB  - The phase study of a Cd-Yb 1/1 approximant crystal over a wide pressure and
      temperature range is crucial for the comparison study between periodic and
      quasiperiodic crystals. The Cd(4) tetrahedra, the most inner part of the atomic
      clusters, exhibited various structural ordering in the orientation sensitive to
      pressure and temperature. Five ordered phases appeared in a P-T span up to 5.2
      GPa and down to 10 K. The propagation direction of ordering alternated from [110]
      to <111> to at about 1.0 GPa and again to [110] at 3.5-4.3 GPa. The primarily
      ordered phases that appeared by cooling to 210-250 K between 1.0-5.2 GPa further
      transformed to finely ordered ones at 120-155 K. Besides the original short-range
      type interaction, a long-range type interaction was likely developed under
      pressure to lead to the primary ordering of Cd(4) tetrahedra. Coexistence of
      these interactions is responsible for the complicated phase behavior.

PMID- 16605762
TI  - Single atomic contact adhesion and dissipation in dynamic force microscopy.
AB  - By combining dynamic force microscopy experiments and first-principles
      calculations, we have studied the adhesion associated with a single atomic
      contact between a nanoasperity--the tip apex--and a semiconductor surface--the
      Ge(111)-c(2 x 8). The nanoasperity's termination has been atomically
      characterized by extensive comparisons of the measured short-range force at
      specific sites with the chemical forces calculated using many atomic models that
      vary in structure, composition, and relative orientation with respect to the
      surface. This thorough characterization has allowed us to explain the dissipation
      signal observed in atomic-resolution images and force spectroscopic measurements,
      as well as to identify a dissipation channel and the associated atomic processes.

PMID- 16605763
TI  - Self-ordering of a Ge island single layer induced by Si overgrowth.
AB  - We provide a direct experimental proof and the related modeling of the role
      played by Si overgrowth in promoting the lateral ordering of Ge islands grown by
      chemical vapor deposition on Si(001). The deposition of silicon induces a shape
      transformation, from domes to truncated pyramids with a larger base, generating
      an array of closely spaced interacting islands. By modeling, we show that the
      resulting gradient in the chemical potential across the island should be the
      driving force for a selective flow of both Ge and Si atoms at the surface and, in
      turn, to a real motion of the dots, favoring the lateral order.

PMID- 16605764
TI  - Superior regularity in erosion patterns by planar subsurface channeling.
AB  - The onset of pattern formation through exposure of Pt(111) with 5 keV Ar(+) ions
      at grazing incidence has been studied at 550 K by scanning tunneling microscopy
      and is supplemented by molecular-dynamics simulations of single ion impacts. A
      consistent description of pattern formation in terms of atomic scale mechanisms
      is given. Most surprisingly, pattern formation depends crucially on the angle of
      incidence of the ions. As soon as this angle allows subsurface channeling of the
      ions, pattern regularity and alignment with respect to the ion beam greatly
      improves. These effects are traced back to the positionally aligned formation of
      vacancy islands through the damage created by the ions at dechanneling locations.

PMID- 16605765
TI  - Origin of p(2 x 1) phase on Si(001) by noncontact atomic force microscopy at 5 k.
AB  - The controversial issue of the origin of the p(2 x 1) reconstruction of the
      Si(001) surface observed in recent low temperature scanning tunneling microscopy
      experiments is clarified here using 5 K noncontact atomic force microscopy. The
      c(4 x 2) phase is observed at separations corresponding to weak tip-surface
      interactions, confirming that it is the ground state of the surface. At larger
      frequency shifts the p(2 x 1) phase of symmetric dimers is observed. By studying
      the interaction of a reactive Si tip with the c(4 x 2) Si(001) surface using an
      ab initio method, we find that the observed change in the surface reconstruction
      is an apparent effect caused by tip induced dimer flipping resulting in a
      modification of the surface structure and appearance of the p(2 x 1) phase in the
      image. Using an appropriate scanning protocol, one can manipulate the surface
      reconstruction at will, which has significance in nanotechnology.

PMID- 16605766
TI  - Influence of quantum size effects on island coarsening.
AB  - Surface x-ray scattering and scanning-tunneling microscopy experiments reveal
      novel coarsening behavior of Pb nanocrystals grown on Si(111)-(7 x 7). It is
      found that quantum size effects lead to the breakdown of the classical Gibbs
      Thomson analysis. This is manifested by the lack of scaling of the island
      densities. In addition, island decay times tau are orders of magnitude faster
      than expected from the classical analysis and have an unusual dependence on the
      growth flux F (i.e., tau is approximately 1/F). As a result, a highly
      monodispersed 7-layer island height distribution is found after coarsening if the
      islands are grown at high rather than low flux rates. These results have
      important implications, especially at low temperatures, for the controlled growth
      and self-organization of nanostructures.

PMID- 16605767
TI  - Iron oxidation, interfacial expansion, and buckling at the Fe/NiO(001) interface.
AB  - In order to provide a structural basis for a physical understanding of exchange
      bias in metal/magnetic-oxide interfaces, we have determined the structure of the
      Fe/NiO(001) interface by means of x-ray absorption spectroscopy and ab initio
      density functional theory calculations. A Fe-Ni alloyed phase on top of an
      interfacial FeO planar layer is formed. The FeO layer exhibits a 7% expanded
      interlayer distance and a 0.3 A buckling; its presence is predicted to increase
      the spin magnetic moment of the interface Fe atoms by 0.6 mu(B), compared to the
      ideally abrupt interface.

PMID- 16605768
TI  - Helical liquid and the edge of quantum spin Hall systems.
AB  - The edge states of the recently proposed quantum spin Hall systems constitute a
      new symmetry class of one-dimensional liquids dubbed the "helical liquid," where
      the spin orientation is determined by the direction of electron motion. We prove
      a no-go theorem which states that a helical liquid with an odd number of
      components cannot be constructed in a purely 1D lattice system. In a helical
      liquid with an odd number of components, a uniform gap in the ground state can
      appear when the time-reversal symmetry is spontaneously broken by interactions.
      On the other hand, a correlated two-particle backscattering term by an impurity
      can become relevant while keeping the time-reversal invariance.

PMID- 16605769
TI  - Energy dispersion of 4f-derived emissions in photoelectron spectra of the heavy
      fermion compound YbIr2Si2.
AB  - Angle-resolved photoemission spectra of the heavy-fermion system YbIr(2)Si(2) are
      reported that reveal strong momentum (k) dependent splittings of the 4f(13) bulk
      and surface emissions around the expected intersection points of the 4f final
      states with valence bands in the Brillouin zone. The obtained dispersion is
      explained in terms of a simplified periodic Anderson model by a k dependence of
      the electron hopping matrix element disregarding clearly interpretation in terms
      of a single-impurity model.

PMID- 16605770
TI  - Photoinduced transient stark spectroscopy in organic semiconductors: a method for
      charge mobility determination in the picosecond regime.
AB  - Subpicosecond photoinduced Stark spectroscopy experiments are carried out for
      measuring charge carrier mobility in organic semiconductors. The technique is
      demonstrated in state-of-art devices based on methanofullerene. The transient
      mobility of photogenerated charge carriers is measured in the picosecond time
      domain. Electric field dependent mobility is observed from the earliest time
      scales. In addition, two distinct transport regimes are revealed: a short-lived
      state, approximately 10 ps, of high mobility and a transient towards the trap
      limited transport, associated with the mesoscopic structure of the medium.

PMID- 16605771
TI  - Using qubits to measure fidelity in mesoscopic systems.
AB  - We point out the similarities in the definition of the "fidelity" of a quantum
      system and the generating function determining the full counting statistics of
      charge transport through a quantum wire and suggest to use flux or charge qubits
      for their measurement. As an application we use the notion of fidelity within a
      first-quantized formalism in order to derive new results and insights on the
      generating function of the full counting statistics.

PMID- 16605772
TI  - Quantum spin Hall effect.
AB  - The quantum Hall liquid is a novel state of matter with profound emergent
      properties such as fractional charge and statistics. The existence of the quantum
      Hall effect requires breaking of the time reversal symmetry caused by an external
      magnetic field. In this work, we predict a quantized spin Hall effect in the
      absence of any magnetic field, where the intrinsic spin Hall conductance is
      quantized in units of 2(e/4pi). The degenerate quantum Landau levels are created
      by the spin-orbit coupling in conventional semiconductors in the presence of a
      strain gradient. This new state of matter has many profound correlated properties
      described by a topological field theory.

PMID- 16605773
TI  - Mesoscopic resonating valence bond system on a triple dot.
AB  - We theoretically introduce a mesoscopic pendulum from a triple dot. The pendulum
      is fastened through a singly occupied dot (spin qubit). Two other strongly
      capacitively coupled islands form a double-dot charge qubit with one electron in
      excess oscillating between the two low-energy charge states (1,0) and (0,1). The
      triple dot is placed between two superconducting leads. Under realistic
      conditions, the main proximity effect stems from the injection of resonating
      singlet (valence) bonds on the triple dot. This gives rise to a Josephson current
      that is charge- and spin-dependent and, as a consequence, exhibits a distinct
      resonance as a function of the superconducting phase difference.

PMID- 16605774
TI  - Tuning the electrical conductivity of nanotube-encapsulated metallocene wires.
AB  - We analyze a new family of carbon nanotube-based molecular wires, formed by
      encapsulating metallocene molecules inside the nanotubes. Our simulations, which
      are based on a combination of nonequilibrium Green function techniques and
      density functional theory, indicate that these wires can be engineered to exhibit
      desirable magnetotransport effects for use in spintronics devices. The proposed
      structures should also be resilient to room-temperature fluctuations, and are
      expected to have a high yield.

PMID- 16605775
TI  - Intrinsic and extrinsic effects in the temperature-dependent photoluminescence of
      semiconducting carbon nanotubes.
AB  - The temperature dependence of the band gap of semiconducting carbon nanotubes was
      measured for ten different nanotube species. The unprecedented effectiveness in
      avoiding the effect of external strain, or any other effects originating from the
      surrounding environment, lead to an accurate measurement of the band gap
      temperature dependence, giving fundamental insight into the nanotube electron
      phonon interaction. Small but reproducible energy shifts of the emission lines
      with temperature were observed, showing a moderate chirality dependence, well in
      agreement with recent theoretical calculations. In addition to the energy shift,
      a substantial narrowing of the emission lines was also observed. The removal of
      the temperature shift of the band gap allows the precise measurement of the
      effect of external strain on carbon nanotubes in different environments.

PMID- 16605776
TI  - Parametric control of a superconducting flux qubit.
AB  - Parametric control of a superconducting flux qubit has been achieved by using two
      frequency microwave pulses. We have observed Rabi oscillations stemming from
      parametric transitions between the qubit states when the sum of the two microwave
      frequencies or the difference between them matches the qubit Larmor frequency. We
      have also observed multiphoton Rabi oscillations corresponding to one- to four
      photon resonances by applying single-frequency microwave pulses. The parametric
      control demonstrated in this work widens the frequency range of microwaves for
      controlling the qubit and offers a high quality testing ground for exploring
      nonlinear quantum phenomena of macroscopically distinct states.

PMID- 16605777
TI  - Non-fermi liquid and pairing in electron-doped cuprates.
AB  - We study the normal state and pairing instability in electron-doped cuprates in a
      model with long-ranged antiferromagnetic spin fluctuations close to an
      antiferromagnetic quantum-critical point. We show that the fermionic self-energy
      has a non-Fermi-liquid form leading to peculiar frequency dependencies of the
      conductivity and the Raman response. We solve the pairing problem and demonstrate
      that T(c) is determined by the curvature of the Fermi surface, and the pairing
      gap delta (kappa, omega) is strongly nonmonotonic along the Fermi surface. The
      normal state frequency dependencies, the value of T(c) is approximately 10 K, and
      the kappa dependence of the gap agree with the experiment.

PMID- 16605778
TI  - Doping controlled superconductor-insulator transition in Bi2Sr2
      xLaxCaCu2O8+delta.
AB  - We show that the doping-controlled superconductor-insulator transition (SIT) in a
      high critical temperature cuprate system (Bi(2)Sr(2-x)La(x)CaCu(2)O(8+delta))
      exhibits a fundamentally different behavior than is expected from conventional
      SIT. At the critical doping, the sheet resistance seems to diverge in the zero
      temperature limit. Above the critical doping, the transport is universally scaled
      by a two-component conductance model. Below, it continuously evolves from weakly
      to strongly insulating behavior. The two-component conductance model suggests
      that a collective electronic phase-separation mechanism may be responsible for
      this unconventional SIT behavior.

PMID- 16605779
TI  - Charge transfer between a superconductor and a hopping insulator.
AB  - We develop a theory of the low-temperature charge transfer between a
      superconductor and a hopping insulator. We show that the charge transfer is
      governed by the coherent two-electron-Cooper pair conversion process time
      reversal reflection, where electrons tunnel into a superconductor from the
      localized states in the hopping insulator located near the interface, and
      calculate the corresponding interface resistance. A specific feature of this
      problem is the interplay between the time-reversal reflection at the interface
      and transport through the percolation cluster. To allow for this interplay, we
      have generalized the connectivity criterion of the percolation theory to include
      surface effects. We show that the time-reversal interface resistance is
      accessible experimentally, and that in mesoscopic structures it can exceed the
      bulk hopping resistance.

PMID- 16605780
TI  - Collapse of the magnetic gap of cuprate superconductors within a three-band model
      of resonant inelastic x-ray scattering.
AB  - We present a three-band Hubbard Hamiltonian and the associated Cu Kappa-edge
      resonant inelastic x-ray scattering (RIXS) spectra for electron- and hole-doped
      cuprates over a wide range of energy and momentum transfers. By comparing
      computed spectra for the unfilled case with the corresponding results for 15%
      electron or hole doping at two different values of the effective Hubbard
      parameter , generic signatures of the collapse of the magnetic gap and the
      characteristic momentum dependencies and evolution of the spectra with doping are
      identified. Available RIXS data support the gap collapse scenario for electron
      doped cuprates, but the situation in hole-doped systems is found to be less
      clear.

PMID- 16605781
TI  - Nondispersive fermi arcs and the absence of charge ordering in the pseudogap
      phase of Bi2Sr2CaCu2O8+delta.
AB  - The autocorrelation of angle resolved photoemission data from the high
      temperature superconductor Bi(2)Sr(2)CaCu(2)O(8+delta) shows distinct peaks in
      momentum space which disperse with binding energy in the superconducting state,
      but not in the pseudogap phase. Although it is tempting to attribute a
      nondispersive behavior in momentum space to charge ordering, a deconstruction of
      the autocorrelation reveals that the nondispersive peaks arise from the tips of
      the Fermi arcs, which themselves do not change with binding energy.

PMID- 16605782
TI  - Experimental proof of a structural origin for the shadow fermi surface of
      Bi2Sr2CaCu2O8+delta.
AB  - By combining surprising new results from a full polarization analysis of nodal
      angle-resolved photoemission data from pristine and modulation-free
      Bi(2)Sr(2)CaCu(2)O(8+delta) with structural information from LEED and ab initio
      one-step photoemission simulations, we prove that the shadow Fermi surface in
      these systems is of structural origin, being due to orthorhombic distortions from
      tetragonal symmetry present both in surface and bulk. Consequently, one of the
      longest standing open issues in the investigation of the Fermi surface of these
      widely studied systems finally meets its resolution.

PMID- 16605783
TI  - Experimental evidence of s-wave superconductivity in bulk CaC6.
AB  - The temperature dependence of the in-plane magnetic penetration depth,
      lambda(ab)(T), has been measured in a c-axis oriented polycrystalline CaC(6) bulk
      sample using a high-resolution mutual inductance technique. A clear exponential
      behavior of lambda(ab)(T) has been observed at low temperatures, strongly
      suggesting isotropic s-wave pairing. Data fit using the standard BCS theory
      yields lambda(ab)(0) = (720 +/- 80) A and delta(0) = (1.79 +/- 0.08) meV. The
      ratio 2delta(0)/k(B)T(c) = (3.6 +/- 0.2) gives indication for a weakly coupled
      superconductor.

PMID- 16605784
TI  - NMR study of the magnetic and metal-insulator transitions in Na0.5CoO2: a nesting
      scenario.
AB  - Co and Na NMR are used to probe the local susceptibility and charge state of the
      two Co sites of the Na-ordered orthorhombic Na(0.5)CoO(2). Above T(N) = 86 K,
      both sites display a similar T dependence of the spin shift, suggesting that
      there is no charge segregation into Co(3+) and Co(4+) sites. Below T(N), the
      magnetic long range commensurate order found is only slightly affected by the
      metal-insulator transition at T(MIT) = 51 K. Furthermore, the electric field
      gradient at the Co site does not change at these transitions, indicating the
      absence of charge ordering. All these observations can be explained by successive
      spin-density wave induced by two nestings of the Fermi surface specific to the x
      = 0.5 Na ordering.

PMID- 16605785
TI  - Observation of a half step magnetization in the {Cu3}-type triangular spin ring.
AB  - We report pulsed field magnetization and ESR experiments on a {Cu3} nanomagnet,
      where antiferromagnetically coupled Cu(2+) (S = 1/2) ions form a slightly
      distorted triangle. The remarkable feature is the observation of a half step
      magnetization, hysteresis loops, and an asymmetric magnetization between a
      positive and a negative field in a fast sweeping external field. This is
      attributed to an adiabatic change of magnetization. The energy levels determined
      by ESR unveil that the different mixing nature of a spin chirality of a total S =
      1/2 Kramers doublet by virtue of Dzyaloshinskii-Moriya interactions is decisive
      for inducing half step magnetization.

PMID- 16605786
TI  - Magnetism without magnetic ions: percolation, exchange, and formation energies of
      magnetism-promoting intrinsic defects in CaO.
AB  - We investigate theoretically the prospects of ferromagnetism being induced by
      cation vacancies in nonmagnetic oxides. A single Ca vacancy V(0)(Ca) has a
      magnetic moment due to its open-shell structure but the ferromagnetic interaction
      between two vacancies extends only to four neighbors or less. To achieve magnetic
      percolation on a fcc lattice with such an interaction range one needs a minimum
      of 4.9% vacancies, or a concentration 1.8 x 10(21) cm(-3). Total-energy
      calculations for CaO show, however, that due to the high vacancy formation energy
      even under the most favorable growth conditions one can not obtain more than
      0.003% or 10(18) cm(-3) vacancies at equilibrium, showing that a nonequilibrium
      vacancy-enhancement factor of 10(3) is needed to achieve magnetism in such
      systems.

PMID- 16605787
TI  - Dynamical electric and magnetic metamaterial response at terahertz frequencies.
AB  - Utilizing terahertz time domain spectroscopy, we have characterized the
      electromagnetic response of a planar array of split ring resonators (SRRs)
      fabricated upon a high resistivity GaAs substrate. The measured frequency
      dependent magnetic and electric resonances are in excellent agreement with theory
      and simulation. For two polarizations, the SRRs yield a negative electric
      response (epsilon < 0). We demonstrate, for the first time, dynamical control of
      the electrical response of the SRRs through photoexcitation of free carriers in
      the substrate. An excited carrier density of approximately 4 x 10(16) cm(-3) is
      sufficient to short the gap of the SRRs, thereby turning off the electric
      resonance, demonstrating the potential of such structures as terahertz switches.
      Because of the universality of metamaterial response over many decades of
      frequency, these results have implications for other regions of the
      electromagnetic spectrum.

PMID- 16605788
TI  - Nested fermi surface and electronic instability in Ca3Ru2O7.
AB  - High-resolution angular resolved photoemission data reveal well-defined
      quasiparticle bands of unusually low weight, emerging in line with the metallic
      phase of Ca(3)Ru(2)O(7) below approximately 30 K . At the bulk structural phase
      transition temperature of 48 K, we find clear evidence for an electronic
      instability, gapping large parts of the underlying Fermi surface that appears to
      be nested. Metallic pockets are found to survive in the small, non-nested
      sections, constituting a low-temperature Fermi surface with 2 orders of magnitude
      smaller volume than in all other metallic ruthenates. The Fermi velocities and
      volumes of these pockets are in agreement with the results of complementary
      quantum oscillation measurements on the same crystal batches.

PMID- 16605789
TI  - Propulsion of ripples on glass by ion bombardment.
AB  - The propulsion of surface ripples on SiO(2) by an ion beam was investigated by in
      situ electron microscopy. The observed propagation of the ripples contradicts
      existing models for ion-beam-induced ripple development. A new model based on the
      Navier-Stokes relations for viscous flow in a thin layer is introduced. It
      includes inhomogeneous viscous flow, driven by spatial variations in the
      deposition of the energy of the ion beam. The model explains the observed
      reversed propagation. The hitherto unknown propulsion mechanism is important for
      understanding nanoscale pattern formation by ion bombardment.

PMID- 16605790
TI  - Ionic polarizability of conductive metal oxides and critical thickness for
      ferroelectricity in BaTiO3.
AB  - We report a first-principles investigation of ultrathin BaTiO(3) films with
      SrRuO(3) electrodes. We find that the ionic relaxations in the metal-oxide
      electrode play a crucial role in stabilizing the ferroelectric phase. Comparison
      with frozen-phonon calculations shows that the degree of softness of the SrRuO(3)
      lattice has an essential impact on the screening of ferroelectric polarization in
      BaTiO(3). The critical thickness for ferroelectricity in BaTiO(3) is found to be
      1.2 nm. The results of our calculations provide a possible explanation for the
      beneficial impact of oxide electrodes on the switching and dielectric properties
      of ferroelectric capacitors.

PMID- 16605791
TI  - Segment distributions of end-tethered polymers in a good solvent.
AB  - We use confocal fluorescence microscopy to study the conformation of single DNA
      molecules end-tethered to a solid substrate. The segment distribution rho(z)
      measured for chains with contour lengths 15.4 microm <or= L <or= 59.4 microm as a
      function of the distance from the substrate can be scaled onto a master curve
      depending only on the scaled distance z/R(g), in quantitative agreement with
      theoretical predictions for end-tethered polymers in a good solvent. The scaling
      of the radius of gyration R(g) approximately L(0.57+/-0.05) shows the presence of
      excluded-volume interactions between the charged DNA segments. Independent
      measurements of R(g) from end-segment distributions are in good agreement with
      values obtained from the segment distributions and provide evidence that the
      radius of gyration of end-tethered chains in a good solvent is identical to that
      of the free chain.

PMID- 16605792
TI  - Dynamics of chain molecules in disordered materials.
AB  - The dynamic behavior of hard chains in disordered materials composed of fixed
      hard spheres is studied using discontinuous molecular dynamics simulations. The
      matrix induces entanglements in the chain fluid, i.e., for high matrix densities
      the diffusion coefficient D scales with the chain length N as D is approximately
      N(-2). At high matrix densities the rotational relaxation time becomes very large
      but the translational diffusion is not affected significantly; i.e., the chains
      display a dynamic heterogeneity reminiscent of probe diffusion in supercooled
      liquids and glasses. We show that this is because some chains are trapped, and
      move via a hopping mechanism. There are no signatures of this dynamic
      heterogeneity in the matrix static structure, however, which is identical to that
      of a hard-sphere liquid.

PMID- 16605793
TI  - Intrinsic rates and activation free energies from single-molecule pulling
      experiments.
AB  - We present a unified framework for extracting kinetic information from single
      molecule pulling experiments at constant force or constant pulling speed. Our
      procedure provides estimates of not only (i) the intrinsic rate coefficient and
      (ii) the location of the transition state but also (iii) the free energy of
      activation. By analyzing simulated data, we show that the resulting rates of
      force-induced rupture are significantly more reliable than those obtained by the
      widely used approach based on Bell's formula. We consider the uniqueness of the
      extracted kinetic information and suggest guidelines to avoid over-interpretation
      of experiments.

PMID- 16605794
TI  - Dynamics of structural transformations between lamellar and inverse bicontinuous
      cubic lyotropic phases.
AB  - The liquid crystalline lamellar (L(alpha)) to double-diamond inverse bicontinuous
      cubic (Q(D)(pi)) phase transition for the amphiphile monoelaidin in excess water
      exhibits a remarkable sequence of structural transformations for pressure or
      temperature jumps. Our data imply that the transition dynamics depends on a
      coupling between changes in molecular shape and the geometrical and topological
      constraints of domain size. We propose a qualitative model for this coupling
      based on theories of membrane fusion via stalks and existing knowledge of the
      structure and energetics of bicontinuous cubic phases.

PMID- 16605795
TI  - Intermittency route to rheochaos in wormlike micelles with flow-concentration
      coupling.
AB  - We show experimentally that the route to chaos is via intermittency in a shear
      thinning wormlike micellar system of cetyltrimethylammonium tosylate, where the
      strength of flow-concentration coupling is tuned by the addition of salt sodium
      chloride. A Poincare first return map of the time series and the probability
      distribution of laminar lengths between burst events shows that our data is
      consistent with type-II intermittency. The coupling of flow to concentration
      fluctuations is evidenced by the "butterfly" intensity pattern in small angle
      light scattering (SALS) measurements performed simultaneously with the
      rheological measurements. The scattered depolarized intensity in SALS, sensitive
      to orientational order fluctuations, shows the same time dependence (like
      intermittency) as that of shear stress.

PMID- 16605796
TI  - Proactive robustness control of heterogeneously loaded networks.
AB  - A proactive measure to increase the robustness of heterogeneously loaded networks
      against cascades of overload failures is proposed. It is based on load-dependent
      weights. Compared to simple hop weights, respective shortest flow paths turn a
      previously heterogeneous load distribution into a more homogeneous one for the
      nodes and links of the network. The use of these flow paths increases the
      networks robustness and at the same time reduces the investment costs into the
      networks capacity layout. These findings are of relevance for critical
      infrastructures like communication and transportation networks.

PMID- 16605797
TI  - Comment on "earthquakes descaled: on waiting time distributions and scaling
      laws".

PMID- 16605799
TI  - Quantum atom optics with fermions from molecular dissociation.
AB  - We study a fermionic atom optics counterpart of parametric down-conversion with
      photons. This can be realized through dissociation of a Bose-Einstein condensate
      of molecular dimers consisting of fermionic atoms. We present a theoretical model
      describing the quantum dynamics of dissociation and find analytic solutions for
      mode occupancies and atomic pair correlations, valid in the short time limit. The
      solutions are used to identify upper bounds for the correlation functions, which
      are applicable to any fermionic system and correspond to ideal particle number
      difference squeezing.

PMID- 16605800
TI  - Multimode uncertainty relations and separability of continuous variable states.
AB  - A multimode uncertainty relation (generalizing the Robertson-Schrodinger
      relation) is derived as a necessary constraint on the second moments of n pairs
      of canonical operators. In turn, necessary conditions for the separability of
      multimode continuous variable states under (m+n)-mode bipartitions are derived
      from the uncertainty relation. These conditions are proven to be necessary and
      sufficient for (1+n)-mode Gaussian states and for (m+n)-mode bisymmetric Gaussian
      states.

PMID- 16605801
TI  - Strongly interacting Fermi gases with density imbalance.
AB  - We consider density-imbalanced Fermi gases of atoms in the strongly interacting,
      i.e., unitarity, regime. The Bogoliubov-de Gennes equations for a trapped
      superfluid are solved. They take into account the finite size of the system, as
      well as give rise to both phase separation and Fulde-Ferrel-Larkin-Ovchinnikov
      type oscillations in the order parameter. We show how radio-frequency
      spectroscopy reflects the phase separation, and can provide direct evidence of
      the FFLO-type oscillations via observing the nodes of the order parameter.

PMID- 16605802
TI  - Topological entanglement entropy.
AB  - We formulate a universal characterization of the many-particle quantum
      entanglement in the ground state of a topologically ordered two-dimensional
      medium with a mass gap. We consider a disk in the plane, with a smooth boundary
      of length L, large compared to the correlation length. In the ground state, by
      tracing out all degrees of freedom in the exterior of the disk, we obtain a
      marginal density operator rho for the degrees of freedom in the interior. The von
      Neumann entropy of rho, a measure of the entanglement of the interior and
      exterior variables, has the form S(rho) = alphaL - gamma + ..., where the
      ellipsis represents terms that vanish in the limit L --> infinity. We show that -
      gamma is a universal constant characterizing a global feature of the entanglement
      in the ground state. Using topological quantum field theory methods, we derive a
      formula for gamma in terms of properties of the superselection sectors of the
      medium.

PMID- 16605803
TI  - Detecting topological order in a ground state wave function.
AB  - A large class of topological orders can be understood and classified using the
      string-net condensation picture. These topological orders can be characterized by
      a set of data (N, di, F(lmn)(ijk), delta(ijk). We describe a way to detect this
      kind of topological order using only the ground state wave function. The method
      involves computing a quantity called the "topological entropy" which directly
      measures the total quantum dimension D= Sum(id2i).

PMID- 16605804
TI  - Experimental observation of optical rotation generated in vacuum by a magnetic
      field.
AB  - We report the experimental observation of a light polarization rotation in vacuum
      in the presence of a transverse magnetic field. Assuming that data distribution
      is Gaussian, the average measured rotation is (3.9 +/- 0.5) x 10(-12) rad/pass,
      at 5 T with 44 000 passes through a 1 m long magnet, with lambda = 1064 nm. The
      relevance of this result in terms of the existence of a light, neutral, spin-zero
      particle is discussed.

PMID- 16605805
TI  - Photon regeneration from pseudoscalars at X-ray laser facilities.
AB  - Recently, the PVLAS Collaboration reported an anomalously large rotation of the
      polarization of light in the presence of a magnetic field in vacuum. As a
      possible explanation, they consider the existence of a light spin-zero particle
      coupled to two photons. We propose here a method of independently testing this
      result using a high-energy photon regeneration experiment (the x-ray analogue of
      "invisible light shining through walls") using the synchrotron x rays from a free
      electron laser. With such an experiment the region of parameter space implied by
      PVLAS could be probed in a matter of minutes.

PMID- 16605806
TI  - Experimental synchronization of independent entangled photon sources.
AB  - We report the generation of independent entangled photon pairs from two
      synchronized but mutually incoherent laser sources. The quality of
      synchronization is confirmed by observing a violation of Bell's inequality with
      3.2 standard deviations in an entanglement swapping experiment. The techniques
      developed in our experiment are not only important for realistic linear optical
      quantum-information processing, but also enable new tests of local realism.

PMID- 16605807
TI  - Tunable Tsallis distributions in dissipative optical lattices.
AB  - We demonstrated experimentally that the momentum distribution of cold atoms in
      dissipative optical lattices is a Tsallis distribution. The parameters of the
      distribution can be continuously varied by changing the parameters of the optical
      potential. In particular, by changing the depth of the optical lattice, it is
      possible to change the momentum distribution from Gaussian, at deep potentials,
      to a power-law tail distribution at shallow optical potentials.

PMID- 16605808
TI  - Accurate evolutions of orbiting black-hole binaries without excision.
AB  - We present a new algorithm for evolving orbiting black-hole binaries that does
      not require excision or a corotating shift. Our algorithm is based on a novel
      technique to handle the singular puncture conformal factor. This system, based on
      the Baumgarte-Shapiro-Shibata-Nakamura formulation of Einstein's equations, when
      used with a "precollapsed" initial lapse, is nonsingular at the start of the
      evolution and remains nonsingular and stable provided that a good choice is made
      for the gauge. As a test case, we use this technique to fully evolve orbiting
      black-hole binaries from near the innermost stable circular orbit regime. We show
      fourth-order convergence of waveforms and compute the radiated gravitational
      energy and angular momentum from the plunge. These results are in good agreement
      with those predicted by the Lazarus approach.

PMID- 16605809
TI  - Gravitational-wave extraction from an inspiraling configuration of merging black
      holes.
AB  - We present new ideas for evolving black holes through a computational grid
      without excision, which enable accurate and stable evolutions of binary black
      hole systems with the accurate determination of gravitational waveforms directly
      from the wave zone region. Rather than excising the black hole interiors, our
      approach follows the "puncture" treatment of black holes, but utilizing a new
      gauge condition which allows the black holes to move successfully through the
      computational domain. We apply these techniques to an inspiraling binary,
      modeling the radiation generated during the final plunge and ringdown. We
      demonstrate convergence of the waveforms and good conservation of mass-energy,
      with just over 3% of the system's mass converted to gravitational radiation.

PMID- 16605810
TI  - Inflationary predictions for scalar and tensor fluctuations reconsidered.
AB  - We reconsider the predictions of inflation for the spectral index of scalar
      (energy density) fluctuations (ns) and the tensor/scalar ratio (r) using a
      discrete, model-independent measure of the degree of fine-tuning required to
      obtain a given combination of (ns, r ). We find that, except for cases with
      numerous unnecessary degrees of fine-tuning, ns is less than 0.98, measurably
      different from exact Harrison-Zel'dovich. Furthermore, if ns >or= 0.95, in accord
      with current measurements, the tensor/scalar ratio satisfies r >or= 10(-2), a
      range that should be detectable in proposed cosmic microwave background
      polarization experiments and direct gravitational wave searches.

PMID- 16605811
TI  - Radiative decays and the nature of heavy quarkonia.
AB  - We argue that the photon spectra in radiative decays of various heavy quarkonium
      states provide important information on their nature. If two of these states are
      in the strong coupling regime, we are able to produce a parameter-free model
      independent formula, which holds at next-to-leading order and includes both
      direct and fragmentation contributions. When the formula is checked against
      recent CLEO data it favors Y(2S) and Y(3S) in the strong coupling regime and
      disfavors Y(1S) in it.

PMID- 16605812
TI  - Photoabsorption on 4He with a realistic nuclear force.
AB  - The 4He total photoabsorption cross section is calculated with the realistic
      nucleon-nucleon potential Argonne V18 and the three-nucleon force (3NF) Urbana
      IX. Final state interaction is included rigorously via the Lorentz integral
      transform method. A rather pronounced giant resonance with peak cross sections of
      3.0 (3.2) mb is obtained with (without) the 3NF. Above 50 MeV strong 3NF effects,
      up to 35%, are present. Good agreement with experiment is found close to
      threshold. A comparison in the giant resonance region is inconclusive, since data
      do not show a unique picture.

PMID- 16605813
TI  - Efimov effect in nuclear three-body resonance decays.
AB  - We investigate the effects of the nearly fulfilled Efimov conditions on the
      properties of three-body resonances. Using the hyper-spheric adiabatic expansion
      method we compute energy distributions of fragments in a three-body decay of a
      nuclear resonance. As a realistic example we investigate the 1- state in the halo
      nucleus 11Li within a three-body model 9Li + n +n model. Characteristic features
      appear as sharp peaks in the energy distributions. Their origin, as in the Efimov
      effect, is in the large two-body s-wave scattering lengths between the pairs of
      fragments.

PMID- 16605814
TI  - Risk of misinterpretation of nearly degenerate pair bands as chiral partners in
      nuclei.
AB  - The experimental information on the observed nearly degenerate bands in the N =
      75 isotones, in particular 134Pr and 136Pm, which are often considered as the
      best candidates for chiral bands, is critically analyzed. Most properties of the
      bands, in particular, the recently measured branching ratios and lifetimes, are
      in clear disagreement with the interpretation of the two bands as chiral bands.
      For I =14-18 in 134Pr, where the observed energies are almost degenerate, we have
      obtained a value of 2.0(4) for the ratio of the transition quadrupole moments of
      the two bands, which implies a considerable difference in the nuclear shape
      associated with the two bands. The insufficiency of the near-degeneracy criterion
      to trace nuclear chirality is emphasized.

PMID- 16605815
TI  - Probing shell structure and shape changes in neutron-rich sulfur isotopes through
      transient-field g-factor measurements on fast radioactive beams of 38S and 40S.
AB  - The shell structure underlying shape changes in neutron-rich nuclei near N = 28
      has been investigated by a novel application of the transient-field technique to
      measure the first-excited-state g factors in 38S and 40S produced as fast
      radioactive beams. There is a fine balance between proton and neutron
      contributions to the magnetic moments in both nuclei. The g factor of deformed
      40S does not resemble that of a conventional collective nucleus because spin
      contributions are more important than usual.

PMID- 16605816
TI  - Hindrance of heavy-ion fusion due to nuclear incompressibility.
AB  - We propose a new mechanism to explain the unexpected steep falloff of fusion
      cross sections at energies far below the Coulomb barrier. The saturation
      properties of nuclear matter are causing a hindrance to large overlap of the
      reacting nuclei and consequently a sensitive change of the nuclear potential
      inside the barrier. We report in this Letter a good agreement with the data of
      coupled-channels calculation for the 64Ni + 64Ni combination using the double
      folding potential with Michigan-3-Yukawa-Reid effective N - N forces supplemented
      with a repulsive core that reproduces the nuclear incompressibility for total
      overlap.

PMID- 16605817
TI  - Efficient approach to time-dependent density-functional perturbation theory for
      optical spectroscopy.
AB  - Using a superoperator formulation of linearized time-dependent density-functional
      theory, the dynamical polarizability of a system of interacting electrons is
      represented by a matrix continued fraction whose coefficients can be obtained
      from the nonsymmetric block-Lanczos method. The resulting algorithm, which is
      particularly convenient when large basis sets are used, allows for the
      calculation of the full spectrum of a system with a computational workload only a
      few times larger than needed for static polarizabilities within time-independent
      density-functional perturbation theory. The method is demonstrated with
      calculation of the spectrum of benzene, and prospects for its application to the
      large-scale calculation of optical spectra are discussed.

PMID- 16605818
TI  - Enhancement and quenching of single-molecule fluorescence.
AB  - We present an experimental and theoretical study of the fluorescence rate of a
      single molecule as a function of its distance to a laser-irradiated gold
      nanoparticle. The local field enhancement leads to an increased excitation rate
      whereas nonradiative energy transfer to the particle leads to a decrease of the
      quantum yield (quenching). Because of these competing effects, previous
      experiments showed either fluorescence enhancement or fluorescence quenching. By
      varying the distance between molecule and particle we show the first experimental
      measurement demonstrating the continuous transition from fluorescence enhancement
      to fluorescence quenching. This transition cannot be explained by treating the
      particle as a polarizable sphere in the dipole approximation.

PMID- 16605819
TI  - Absorption spectra of quantum aggregates interacting via long-range forces.
AB  - We present a simple formula by which the shape of the absorption spectrum of an
      aggregate of quantum "monomers" (cold atoms, molecules, quantum dots,
      nanoparticles, etc.) interacting via dipole-dipole forces can be calculated from
      the averaged spectrum of the quantum monomer itself. Spectral broadening, due to
      a wide variety of causes, is included explicitly so that the formula is
      applicable not only to the idealization of a discrete spectrum but also to the
      practical situation of a continuously broadened spectrum. In simple cases,
      analytic results are obtained showing the strong dependence of the aggregate
      spectrum on the precise nature of the broadening of the quantum monomer spectrum.
      The formula is compared with results of exact diagonalization of model aggregate
      Hamiltonians and with experiment.

PMID- 16605820
TI  - Structural transformations and melting in neon clusters: quantum versus classical
      mechanics.
AB  - The extraordinary complexity of Lennard-Jones (LJ) clusters, which exhibit
      numerous structures and "phases" when their size or temperature is varied,
      presents a great challenge for accurate numerical simulations, even without
      accounting for quantum effects. To study the latter, we utilize the variational
      Gaussian wave packet method in conjunction with the exchange Monte Carlo sampling
      technique. We show that the quantum nature of neon clusters has a substantial
      effect on their size-temperature "phase diagrams," particularly the critical
      parameters of certain structural transformations. We also give a numerical
      confirmation that none of the nonicosahedral structures observed for some
      classical LJ clusters are favorable in the quantum case.

PMID- 16605821
TI  - Quasi-intrinsic angular momentum and the measurement of its spectrum.
AB  - We introduce the concept of quasi-intrinsic angular momentum to denote fields for
      which the mean value of the angular momentum is unaltered by a lateral shift of
      the rotation axis but the spectrum changes. This property is exemplified by the
      orbital angular momentum of a beam of light about its propagation direction. We
      propose an interferometric experiment to measure efficiently the exact angular
      momentum spectrum and variance for light beams with any arbitrary spatial
      distribution.

PMID- 16605822
TI  - Enhanced soliton transport in quasiperiodic lattices with introduced
      aperiodicity.
AB  - We study linear transmission and nonlinear soliton transport through
      quasiperiodic structures, where the lattice profiles are described by multiple
      modulation frequencies. We show that resonant scattering at mixed-frequency
      resonances limits transmission efficiency of localized wave packets, leading to
      radiation and possible trapping of solitons. We obtain an explicit analytical
      expression for optimal quasiperiodic lattice profiles, where additional aperiodic
      modulations suppress mixed-frequency resonances, resulting in dramatic
      enhancement of soliton mobility. Our results can be applied to the design of
      photonic waveguide structures, and arrays of magnetic micro-traps for atomic Bose
      Einstein condensates.

PMID- 16605823
TI  - Stable optical trapping based on optical binding forces.
AB  - Various trapping configurations have been realized so far, either based on the
      scattering force or the gradient force. In this Letter, we propose a new trapping
      regime based on the equilibrium between a scattering force and optical binding
      forces only. The trap is realized from the interaction between a single plane
      wave and a series of fixed small particles, and is efficient at trapping multiple
      free particles. The effects are demonstrated analytically upon computing the
      exact scattering from a collection of cylindrical particles and calculating the
      Lorentz force on each free particle via the Maxwell stress tensor.

PMID- 16605824
TI  - Spatiotemporal chaos: the microscopic perspective.
AB  - Extended nonequilibrium systems can be studied in the framework of field theory
      or from the dynamical systems perspective. Here we report numerical evidence that
      the sum of a well-defined number of instantaneous Lyapunov exponents for the
      complex Ginzburg-Landau equation is given by a simple function of the space
      average of the square of the macroscopic field. This relationship follows from an
      explicit formula for the time-dependent values of almost all the exponents.

PMID- 16605825
TI  - Synchronization reveals topological scales in complex networks.
AB  - We study the relationship between topological scales and dynamic time scales in
      complex networks. The analysis is based on the full dynamics towards
      synchronization of a system of coupled oscillators. In the synchronization
      process, modular structures corresponding to well-defined communities of nodes
      emerge in different time scales, ordered in a hierarchical way. The analysis also
      provides a useful connection between synchronization dynamics, complex networks
      topology, and spectral graph analysis.

PMID- 16605826
TI  - Viscosity destabilizes sonoluminescing bubbles.
AB  - In single-bubble sonoluminescence (SBSL) microbubbles are trapped in a standing
      sound wave, typically in water or water-glycerol mixtures. However, in viscous
      liquids such as glycol, methylformamide, or sulphuric acid it is not possible to
      trap the bubble in a stable position. This is very peculiar as larger viscosity
      normally stabilizes the dynamics. Suslick and co-workers call this new mysterious
      state of SBSL "moving-SBSL." We identify the history force (a force nonlocal in
      time) as the origin of this destabilization and show that the instability is
      parametric. A force balance model quantitatively accounts for the observed
      quasiperiodic bubble trajectories.

PMID- 16605827
TI  - Folding of viscous threads in diverging microchannels.
AB  - We study the folding instability of a viscous thread surrounded by a less viscous
      miscible liquid flowing from a square to a diverging microchannel. Because of the
      change in the flow introduced by the diverging channel, the viscous thread
      minimizes viscous dissipation by oscillating to form bends rather than by simply
      dilating. The folding frequency and the thread diameter can be related to the
      volume flow rates and thus to the characteristic shear rate. Diffusive mixing at
      the boundary of the thread can significantly modify the folding flow
      morphologies. This microfluidic system enables us to control the bending of the
      thread and to enhance mixing between liquids having significantly different
      viscosities.

PMID- 16605828
TI  - Nanoscale fluid flows in the vicinity of patterned surfaces.
AB  - Molecular dynamics simulations of dense and rarefied fluids comprising small
      chain molecules in chemically patterned nanochannels predict a novel switching
      from Poiseuille to plug flow along the channel. We also demonstrate behavior akin
      to the lotus effect for a nanodrop on a chemically patterned substrate. Our
      results show that one can control and exploit the behavior of fluids at the
      nanoscale using chemical patterning.

PMID- 16605829
TI  - Multifractal dimension of Lagrangian turbulence.
AB  - We report experimental measurements of the Lagrangian multifractal dimension
      spectrum in an intensely turbulent laboratory water flow by the optical tracking
      of tracer particles. The Legendre transform of the measured spectrum is compared
      with measurements of the scaling exponents of the Lagrangian velocity structure
      functions, and excellent agreement between the two measurements is found, in
      support of the multifractal picture of turbulence. These measurements are
      compared with three model dimension spectra. When the nonexistence of structure
      functions of order less than -1 is accounted for, the models are shown to agree
      well with the measured spectrum.

PMID- 16605830
TI  - Efficient propagation of polarization from laser photons to positrons through
      compton scattering and electron-positron pair creation.
AB  - We have demonstrated for the first time the production of highly polarized short
      pulse positrons with a finite energy spread in accordance with a new scheme that
      consists of two-quantum processes, such as inverse Compton scattering and
      electron-positron pair creation. Using a circularly polarized laser beam of 532
      nm scattered off a high-quality, 1.28 GeV electron beam, we have obtained
      polarized positrons with an intensity of 2 x 10(4) e+ /bunch. The magnitude of
      positron polarization has been determined to be 73 +/- 15(stat) +/- 19(syst)% by
      means of a newly designed positron polarimeter.

PMID- 16605831
TI  - Measurement of the interaction force among particles in three-dimensional plasma
      clusters.
AB  - The interaction forces between particles have been studied in a 3D plasma cluster
      under weak external confinement. A suitable combination of dc and rf applied to a
      small electrode provided gravity compensation, uniform over dimensions much
      larger than the cluster itself. The forces acting on the particles could be
      reconstructed due to unique three-dimensional diagnostics, which allow us to
      obtain coordinates and velocities of all the particles simultaneously. The
      measurements yield a maximum (external) confinement force of 1.4 x 10(-15)N and
      interparticle force that is repulsive at short distances and attractive at larger
      distances, with a maximum attractive force of 2.4 X 10(-14)N at particle
      separation 195 microm.

PMID- 16605832
TI  - Spectrum of magnetohydrodynamic turbulence.
AB  - We propose a phenomenological theory of strong incompressible magnetohydrodynamic
      turbulence in the presence of a strong large-scale external magnetic field. We
      argue that in the inertial range of scales, magnetic-field and velocity-field
      fluctuations tend to align the directions of their polarizations. However, the
      perfect alignment cannot be reached; it is precluded by the presence of a
      constant energy flux over scales. As a consequence, the directions of shear
      Alfven fluid and magnetic-field fluctuations at each scale lambda become
      effectively aligned within the angle phi(lambda) proportional to lambda (1/4),
      which leads to scale-dependent depletion of the nonlinear interaction and to the
      field-perpendicular energy spectrum E(k(perpendicular)) proportional to
      k(perpendicular)(-3/2). Our results may be universal, i.e., independent of the
      external magnetic field, since small-scale fluctuations locally experience a
      strong field produced by large-scale eddies.

PMID- 16605833
TI  - Streamers in the JIPP T-llU tokamak plasmas.
AB  - It is shown that the low-density Ohmically heated tokamak plasmas have
      streamerlike eddies at the outer region at normalized minor radius of about 0.7
      and high-frequency zonal flows of large amplitudes in the core. The amplitudes of
      the eddies ePhi/kT(e) and n(e)/n(e) are of order of 0.5, similar to that of blobs
      in the tokamak plasma boundary. The waveforms are featured by pulses of complex
      shape with sharp fronts, similar to the results of streamer simulations by Garbet
      et al.. The time constant of the fronts is also in agreement with the simulation.
      The radial span of the eddies is estimated to be much larger than the poloidal
      span.

PMID- 16605834
TI  - Early out-of-equilibrium beam-plasma evolution.
AB  - We solve analytically the out-of-equilibrium initial stage that follows the
      injection of a radially finite electron beam into a plasma at rest and test it
      against particle-in-cell simulations. For initial large beam edge gradients and
      not too large beam radius, compared to the electron skin depth, the electron beam
      is shown to evolve into a ring structure. For low enough transverse temperatures,
      the filamentation instability eventually proceeds and saturates when transverse
      isotropy is reached. The analysis accounts for the variety of very recent
      experimental beam transverse observations.

PMID- 16605835
TI  - Test of thermal transport models through dynamic overpressure stabilization of
      ablation-front perturbation growth in laser-driven CH foils.
AB  - Heat-flow-induced dynamic overpressure at the perturbed ablation front of an
      inertial confinement fusion target can stabilize the ablative Richtmyer-Meshkov
      like instability and mitigate the subsequent ablative Rayleigh-Taylor (RT)
      instability. A series of experiments was performed on the OMEGA laser to quantify
      the dynamic overpressure stabilization during the shock transit. Analysis of the
      experimental data using hydrocode simulations shows that the observed oscillatory
      evolution of the ablation-front perturbations depends on Dc, the size of the
      thermal conduction zone, and the fluid velocity in the blowoff region Vb1 that
      are sensitive to the thermal transport model used. We show that the simulations
      match the experiment well when the time dependence of the heat-flux inhibition is
      taken into account using a recently developed nonlocal heat-transport model [V.
      N. Goncharov et al., Phys. Plasmas 13, 012702 (2006)].

PMID- 16605836
TI  - Inductive and electrostatic acceleration in relativistic jet-plasma interactions.
AB  - We report on the observation of rapid particle acceleration in numerical
      simulations of relativistic jet-plasma interactions and discuss the underlying
      mechanisms. The dynamics of a charge-neutral, narrow, electron-positron jet
      propagating through an unmagnetized electron-ion plasma was investigated using a
      three-dimensional, electromagnetic, particle-in-cell computer code. The
      interaction excited magnetic filamentation as well as electrostatic plasma
      instabilities. In some cases, the longitudinal electric fields generated
      inductively and electrostatically reached the cold plasma-wave-breaking limit,
      and the longitudinal momentum of about half the positrons increased by 50% with a
      maximum gain exceeding a factor of 2 during the simulation period. Particle
      acceleration via these mechanisms occurred when the criteria for Weibel
      instability were satisfied.

PMID- 16605837
TI  - Novel bidecahedral morphology in gold nanoparticles frozen from liquid.
AB  - A bidecahedral morphology in which two truncated decahedral structures share two
      tetrahedral units, involving two types of symmetric-tilt grain boundaries, is
      observed as a novel and rare morphology of gold nanoparticles frozen from liquid
      in free space. This low-symmetry polyhedral morphology with eight multiply
      twinned domains is intermediate between the icosahedral and decahedral motifs.

PMID- 16605838
TI  - Lattice dynamics of molybdenum at high pressure.
AB  - We have determined the lattice dynamics of molybdenum at high pressure to 37 GPa
      using high-resolution inelastic x-ray scattering. Over the investigated pressure
      range, we find a significant decrease in the H-point phonon anomaly. We also
      present calculations based on density functional theory that accurately predict
      this pressure dependence. Based on these results, we infer that the likely
      explanation for the H-point anomaly in molybdenum is strong electron-phonon
      coupling, which decreases upon compression due to the shift of the Fermi level
      with respect to the relevant electronic bands.

PMID- 16605839
TI  - New growth mode through decorated twin boundaries.
AB  - Scanning tunneling microscopy and low energy electron diffraction were used to
      investigate the growth of partly twinned Ir thin films on Ir(111). A transition
      from the expected layer-by-layer to a defect dominated growth mode with a fixed
      lateral length scale and increasing roughness is observed. During growth, the
      majority of the film is stably transformed to twinned stacking. This transition
      is initiated by the energetic avoidance of the formation of intrinsic stacking
      faults compared to two independent twin faults. The atomistic details of the
      defect kinetics are outlined.

PMID- 16605840
TI  - First-principles calculations of vibrational lifetimes and decay channels:
      hydrogen-related modes in Si.
AB  - The vibrational lifetimes and decay channels of local vibrational modes are
      calculated from first principles at various temperatures. Our method can be used
      to predict the temperature dependence of the lifetime of any normal mode in any
      crystal. We focus here on the stretch modes of H2*, H+(BC), and VH x HV in Si.
      The frequencies are almost identical, but the lifetimes vary from 4 to 295 ps.
      The calculations correctly predict the lifetimes for T > 50 K and illustrate the
      critical importance of pseudolocal modes in the decay processes of high-frequency
      local vibrational modes.

PMID- 16605841
TI  - Acoustic pulse echoes probed with time-resolved X-ray triple-crystal
      diffractometry.
AB  - Acoustic pulse echoes generated by femtosecond laser irradiation were detected
      using time-resolved x-ray triple-crystal diffractometry. The determined time
      dependent longitudinal strain component for pulse echoes in silicon and gallium
      arsenide plates showed that the polarity of the strain pulse was dependent on the
      optically induced initial stress, and that the bipolar pulse waveform was
      gradually deformed and broadened in the course of propagation. The three
      dimensional wave front distortion of pulse echoes was shown simply as the pulse
      duration broadening, which was consistent with a boundary roughness for an
      unpolished plate.

PMID- 16605842
TI  - Scaling relations for logarithmic corrections.
AB  - Multiplicative logarithmic corrections to scaling are frequently encountered in
      the critical behavior of certain statistical-mechanical systems. Here, a Lee-Yang
      zero approach is used to systematically analyze the exponents of such logarithms
      and to propose scaling relations between them. These proposed relations are then
      confronted with a variety of results from the literature.

PMID- 16605843
TI  - Direct identification of critical clusters in chemical vapor deposition.
AB  - The kinetics of heteroepitaxial island nucleation on the Si(111) surface during
      ultrahigh vacuum chemical vapor deposition with the precursor GeH4 was studied by
      scanning tunneling microscopy. The results can be described within the framework
      of rate-equation based nucleation theory, modified by an additional energetic
      barrier for the attachment of adatoms at steps. This barrier results from the
      passivation of steps by dissociation products from the GeH4 precursor. A critical
      nucleus size of 9 atoms is derived. Scanning tunneling microscopy images provide
      direct evidence for the existence of stable clusters consisting of 10 atoms and
      allow the unequivocal identification of their structure.

PMID- 16605844
TI  - Two-site entropy and quantum phase transitions in low-dimensional models.
AB  - We propose a new approach to study quantum phase transitions in low-dimensional
      lattice models. It is based on studying the von Neumann entropy of two
      neighboring central sites in a long chain. It is demonstrated that the procedure
      works equally well for fermionic and spin models, and the two-site entropy is a
      better indicator of quantum phase transition than calculating gaps, order
      parameters, or the single-site entropy. The method is especially convenient when
      the density-matrix renormalization-group algorithm is used.

PMID- 16605845
TI  - Subgap collective tunneling and its staircase structure in charge density waves.
AB  - Tunneling spectra of chain materials NbSe3 and TaS3 were studied in nanoscale
      mesa devices. Current-voltage I-V characteristics related to all charge density
      waves (CDWs) reveal universal spectra within the normally forbidden region of low
      V, below the electronic CDW gap 2Delta. The tunneling always demonstrates a
      threshold Vt approximately 0.2Delta, followed, for both CDWs in NbSe3, by a
      staircase fine structure. T dependencies of Vt(T) and Delta(T) scale together for
      each CDW, while the low T values Vt(0) correlate with the CDWs' transition
      temperatures Tp. Fine structures of CDWs perfectly coincide when scaled along
      V/Delta. The results evidence the sequential entering of CDW vortices
      (dislocations) in the junction area with the tunneling current concentrated in
      their cores. The subgap tunneling proceeds via the phase channel: coherent phase
      slips at neighboring chains.

PMID- 16605846
TI  - Mott-Anderson transition controlled by a magnetic field in pyrochlore molybdate.
AB  - The pyrochlore molybdate Gd2MO2O7 locates near the phase boundary between the
      ferromagnetic-metallic and the spin-glass insulating state. This metal-insulator
      transition is governed on a large energy scale by the electron-correlation
      effect, while the geometrical frustration causes the random potential. The
      magnetic field can tune the randomness of the potential and control, under a
      suitable pressure, the continuous Mott-Anderson transition precisely. The
      critical exponent (mu = 1.04 +/- 0.1) of the Mott-Anderson transition has been
      determined for this ferromagnetic orbital-degenerate electron system.

PMID- 16605847
TI  - Critical phenomena and the quantum critical point of ferromagnetic Zr(1-x)NbxZn2.
AB  - We present a study of the magnetic properties of Zr(1-x)NbxZn2, using an Arrott
      plot analysis of the magnetization. The Curie temperature Tc is suppressed to
      zero temperature for Nb concentration xc = 0.083+/-0.002, while the spontaneous
      moment vanishes linearly with Tc as predicted by the Stoner theory. The initial
      susceptibility chi displays critical behavior for x <or= xc , with a critical
      exponent which smoothly crosses over from the mean field to the quantum critical
      value. For high temperatures and x <or= xc, and for low temperatures and x >or=
      xc we find that chi(-1) = chi0(-1) + aT(4/3), where chi0(-1) vanishes as x-->xc.
      The resulting magnetic phase diagram shows that the quantum critical behavior
      extends over the widest range of temperatures for x=xc, and demonstrates how a
      finite transition temperature ferromagnet is transformed into a paramagnet, via a
      quantum critical point.

PMID- 16605848
TI  - Orbital ordering in LaMnO3 : electron-electron versus electron-lattice
      interactions.
AB  - The relative importance of electron-lattice (e-l) and electron-electron (e-e)
      interactions in ordering orbitals in LaMnO3 is systematically examined within the
      local-density approximation + Hubbard U approximation of density functional
      theory. A realistic effective Hamiltonian is derived from novel Wannier state
      analysis of the electronic structure. Surprisingly, e-l interaction
      (approximately or = 0.9 eV) alone is found insufficient to stabilize the orbital
      ordered state. On the other hand, e-e interaction (approximately or = 1.7 eV) not
      only induces orbital ordering, but also greatly facilitates the Jahn-Teller
      distortion via enhanced localization. Further experimental means to quantify the
      competition between these two mechanisms are proposed.

PMID- 16605849
TI  - Experimental investigation of the breakdown of the Onsager-Casimir relations.
AB  - We use magnetoconductance fluctuation measurements of phase-coherent
      semiconductor billiards to quantify the contributions to the nonlinear electric
      conductance that are asymmetric under reversal of magnetic field. We find that
      the average asymmetric contribution is linear in magnetic field (for magnetic
      flux much larger than 1 flux quantum) and that its magnitude depends on billiard
      geometry. In addition, we find an unexpected asymmetry in the power spectrum of
      the magnetoconductance with respect to reversal of magnetic field and bias
      voltage.

PMID- 16605850
TI  - Electron states in a lattice of Au nanoparticles: the role of strain and
      functionalization.
AB  - We make use of first-principles calculations to study the effects of
      functionalization and compression on the electronic properties of 2D lattices of
      Au nanoparticles. We consider Au38 particles capped by methylthiol molecules and
      possibly functionalized by the dithiolated conjugated molecules
      benzenedimethanethiol and benzenedicarbothialdehyde. We find that the
      nonfunctionalized lattices are insulating, with negligible band dispersions even
      for a compression of 20% of the lattice constant. Distinct behaviors of the
      dispersion of the lowest conduction band as a function of compression are
      predicted for functionalized lattices: The band dispersion of the
      benzenedimethanethiol-functionalized lattice increases considerably with
      compression, while that of the benzenedicarbothialdehyde-functionalized lattice
      decreases.

PMID- 16605851
TI  - Pressure dependence of the Fulde-Ferrell-Larkin-Ovchinnikov state in CeCoIn5.
AB  - Pressure studies of the thermodynamics of CeCoIn5 under magnetic fields H
      parallel to c and H parallel to ab have been made up to P = 1.34 GPa. We recorded
      the signature of the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state for all
      pressures when H parallel to ab. Also remarkably, the FFLO regime suddenly
      expands for P = 1.34 GPa. With the help of a microscopic theory for d-wave
      superconductivity, we have extracted the gyromagnetic ratio g and the Fermi
      velocities nu(a) and nu(c). Our study is the first evidence for the existence of
      the FFLO state away from the influence of the antiferromagnetic fluctuations. We
      find a close parallel between the T-P phase diagram of CeCoIn5 and the T-x phase
      diagram of the high-Tc cuprates, where x is the hole concentration.

PMID- 16605853
TI  - Phase coexistence and resistivity near the ferromagnetic transition of
      manganites.
AB  - Pairing of oxygen holes into heavy bipolarons in the paramagnetic phase and their
      magnetic pair breaking in the ferromagnetic phase (the so-called current-carrier
      density collapse) has accounted for the first-order ferromagnetic-phase
      transition, colossal magnetoresistance, isotope effect, and pseudogap in doped
      manganites. Here we propose an explanation of the phase coexistence and describe
      the magnetization and resistivity of manganites near the ferromagnetic transition
      in the framework of the current-carrier density collapse. The present
      quantitative description of resistivity is obtained without any fitting
      parameters, by using the experimental resistivities far away from the transition
      and the experimental magnetization, and is essentially model-independent.

PMID- 16605852
TI  - Superconductivity in a molecular metal cluster compound.
AB  - Compelling evidence for band-type conductivity and even bulk superconductivity
      below Tc approximately 8 K has been found in (69,71)Ga NMR experiments in
      crystalline ordered, giant Ga84 cluster compounds. This material appears to
      represent the first realization of a theoretical model proposed by Friedel in
      1992 for superconductivity in ordered arrays of weakly coupled, identical metal
      nanoparticles.

PMID- 16605854
TI  - Kinks, nodal bilayer splitting, and interband scattering in YBa2Cu3O(6+x).
AB  - We apply the new-generation angle-resolved photoemission spectroscopy methodology
      to the most widely studied cuprate superconductor YBa2Cu3O(6+x). Considering the
      nodal direction, we found noticeable renormalization effects known as kinks both
      in the quasiparticle dispersion and scattering rate, the bilayer splitting, and
      evidence for strong interband scattering--all the characteristic features of the
      nodal quasiparticles detected earlier in Bi2Sr2CaCu2O(8+delta). The typical
      energy scale and the doping dependence of the kinks clearly point to their
      intimate relation with the spin-1 resonance seen in the neutron scattering
      experiments. Our findings strongly suggest a universality of the electron
      dynamics in the bilayer superconducting cuprates and a dominating role of the
      spin fluctuations in the formation of the quasiparticles along the nodal
      direction.

PMID- 16605855
TI  - 0-pi transitions in Josephson junctions with antiferromagnetic interlayers.
AB  - We show that the dc Josephson current through superconductor-antiferromagnet
      superconductor (S-AF-S) junctions manifests a remarkable atomic-scale dependence
      on the interlayer thickness. At low temperatures the junction is either a 0 or pi
      junction depending on whether the AF interlayer consists of an even or odd number
      of atomic layers. This is associated with different symmetries of the AF
      interlayers in the two cases. In the junction with odd AF interlayers an
      additional pi- 0 transition can take place as a function of temperature. This
      originates from the interplay of spin-split Andreev bound states. Experimental
      implications of these theoretical findings are discussed.

PMID- 16605856
TI  - Local tunneling spectroscopy as a signature of the Fulde-Ferrell-Larkin
      Ovchinnikov state in s- and d-wave superconductors.
AB  - The Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) states for two-dimensional s- and d
      wave superconductors (s- and d-SCs) are self-consistently studied under an in
      plane magnetic field. While the stripe solution of the order parameter is found
      to have lower free energy in s-SCs, a square lattice solution appears to be
      energetically more favorable in the case of d-SCs. At certain symmetric sites, we
      find that the features in the local density of states (LDOS) can be ascribed to
      two types of bound states. We also show that the LDOS maps for d-SCs exhibit bias
      energy-dependent checkerboard patterns. These characteristics can serve as
      signatures of the FFLO states.

PMID- 16605857
TI  - Charge and magnetization inhomogeneities in diluted magnetic semiconductors.
AB  - It is predicted that III-V diluted magnetic semiconductors can exhibit stripelike
      modulations of magnetization and carrier concentration. This inhomogeneity
      results from the strong dependence of the magnetization on the carrier
      concentration. Within Landau theory, a characteristic temperature T* below the
      Curie temperature is found so that below T* the equilibrium magnetization shows
      modulations, which are strongly anharmonic. The wavelength and amplitude of the
      modulation rise for decreasing temperature, starting from zero at T*. Above T*,
      the equilibrium state is homogeneous, but the coupling between charge and
      magnetization leads to the appearance of an electrically charged layer in domain
      walls.

PMID- 16605858
TI  - Instanton analysis of hysteresis in the three-dimensional random-field Ising
      model.
AB  - We study the magnetic hysteresis in the random-field Ising model in 3D. We
      discuss the disorder dependence of the coercive field Hc, and obtain an
      analytical description of the smooth part of the hysteresis below and above Hc,
      by identifying the disorder configurations (instantons) that are the most
      probable to trigger local avalanches. We estimate the critical disorder strength
      at which the hysteresis curve becomes continuous. From an instanton analysis at
      zero field we obtain a description of local two-level systems in the
      ferromagnetic phase.

PMID- 16605859
TI  - Motional-narrowing-type dephasing of electron and hole spins of itinerant
      excitons in magnetically doped II-VI bulk semiconductors.
AB  - Time-resolved optical spin-quantum-beat measurements performed on magnetically
      doped II-VI bulk semiconductors reveal an increase of the electron spin dephasing
      time with rising temperature typical for motional narrowing. With the dephasing
      being notably faster than in undoped II-VI semiconductors, the magnetic dopants
      must play a key role, modifying the known dephasing mechanisms and introducing
      new ones. Focusing on the latter, we theoretically explore the spin dephasing
      channel arising from magnetization fluctuations sampled by the itinerant
      excitons. This mechanism suffices to explain quantitatively the results of our
      time-resolved Faraday-rotation experiments on optically excited Cd(1-x)Mn(x)Te
      which we present here as a function of magnetic field, temperature and manganese
      dopant density. In addition to electron spin-quantum beats, some of our
      experiments reveal hole spin beats as well.

PMID- 16605860
TI  - Enhancing exchange bias with diluted antiferromagnets.
AB  - The exchange bias H(E) of coupled polycrystalline films of antiferromagnetic CoO
      and ferromagnetic Co was significantly enhanced by the systematic substitution of
      nonmagnetic Mg for Co in CoO. Samples in which either Co or Co(1-x)Mg(x)O were
      deposited first were investigated at temperatures from 10 to 300 K. With Co(1
      x)Mg(x)O on the bottom, the increased interfacial uncompensated spin density of
      the single antiferromagnetic domain Co(1x)Mg(x)O crystallites produced the
      enhanced H(E). With Co on the bottom, a thin interfacial oxide layer was
      primarily responsible for the strongly increased H(E).

PMID- 16605861
TI  - Magnetization plateaus induced by a coupling to the lattice.
AB  - We present a novel mechanism for the appearance of magnetization plateaus in
      quasi-one-dimensional quantum spin systems, which is induced by the coupling to
      the underlying lattice. We investigate in detail a simple model of a frustrated
      spin-1/2 Heisenberg chain coupled to adiabatic phonons under an external magnetic
      field, but the present mechanism is expected to be more general. Using field
      theoretic methods complemented by extensive density matrix renormalization group
      techniques, we show that magnetization plateaus at nontrivial rational values of
      the magnetization can be stabilized by the lattice coupling. We suggest that such
      a scenario could be relevant for some low dimensional frustrated spin-Peierls
      compounds.

PMID- 16605862
TI  - Localized excitation in the hybridization gap in YbAl3.
AB  - The intermediate valence compound YbAl3 exhibits a broad magnetic excitation in
      the inelastic neutron scattering spectrum with characteristic energy E1
      approximately 50 meV, equal to the Kondo energy (T(K) approximately 600-700 K).
      In the low temperature (T < T(coh) approximately 40 K) Fermi liquid state,
      however, a new peak in the scattering occurs at E2 approximately 33 meV, which
      lies in the hybridization gap that exists in this compound. We report inelastic
      neutron scattering results for a single-crystal sample. The scattering at
      energies near E1 qualitatively has the momentum (Q) dependence expected for
      interband scattering across the indirect gap. The scattering near E2 has a very
      different Q dependence: it is a weak function of Q over a large fraction of the
      Brillouin zone and is smallest near (1/2,1/2, 1/2). A possibility is that the
      peak at E2 arises from a spatially localized excitation in the hybridization gap.

PMID- 16605863
TI  - Angle-dependent x-ray magnetic circular dichroism from (Ga,Mn)As: anisotropy and
      identification of hybridized states.
AB  - Remarkably anisotropic Mn L2,3 x-ray magnetic circular dichroism spectra from the
      ferromagnetic semiconductor (Ga,Mn)As are reported. States with cubic and
      uniaxial symmetry are distinguished by careful analysis of the angle dependence
      of the spectra. The multiplet structures with cubic symmetry are qualitatively
      reproduced by calculations for an atomiclike d5 configuration in tetrahedral
      environment, and show zero anisotropy in the orbital and spin moments within the
      experimental uncertainty. However, hybridization with the host valence bands is
      reflected by the presence of a preedge feature with a uniaxial anisotropy and a
      marked dependence on the hole density.

PMID- 16605864
TI  - Berry phase, topology, and degeneracies in quantum nanomagnets.
AB  - A topological theory of the diabolical points (degeneracies) of quantum magnets
      is presented. Diabolical points are characterized by their diabolicity index, for
      which topological sum rules are derived. The paradox of the missing diabolical
      points for Fe8 molecular magnets is clarified. A new method is also developed to
      provide a simple interpretation, in terms of destructive interferences due to the
      Berry phase, of the complete set of diabolical points found in biaxial systems
      such as Fe8.

PMID- 16605865
TI  - Universal distribution of Kondo temperatures in dirty metals.
AB  - Kondo screening of diluted magnetic impurities in a disordered host is studied
      analytically and numerically in one, two, and three dimensions. It is shown that
      in the T(K) --> 0 limit the distribution of Kondo temperatures has a universal
      form P(T(K)) approximately T(K) (-a) that holds in the insulating phase and
      persists in the metallic phase close to the metal-insulator transition. Moreover,
      the exponent depends only on the dimensionality. The most important consequence
      of this result is that the T dependence of thermodynamic properties is smooth
      across the metal-insulator transition in three dimensional systems.

PMID- 16605866
TI  - Evidence of large magnetostructural effects in austenitic stainless steels.
AB  - The surprisingly low magnetic transition temperatures in austenitic stainless
      steels indicate that in these Fe-based alloys magnetic disorder might be present
      at room temperature. Using a first-principles approach, we have obtained a
      theoretical description of the stacking fault energy in Fe(100-c-n)Cr(c)Ni(n)
      alloys as a function of composition and temperature. Comparison of our results
      with experimental databases provides a strong evidence for large magnetic
      fluctuations in these materials. We demonstrate that the effects of alloying
      additions on the structural properties of steels contain a dominant magnetic
      contribution, which stabilizes the most common austenitic steels at normal
      service conditions.

PMID- 16605867
TI  - Spin and orbital quantization of electronic states as origins of second harmonic
      generation in semiconductors.
AB  - Basically different mechanisms of optical second harmonic generation (SHG) in
      semiconductors, induced by an external magnetic field H, have been identified
      experimentally by studying the diluted magnetic semiconductor (Cd,Mn)Te. For
      paramagnetic (Cd,Mn)Te the SHG response is governed by spin quantization of
      electronic states, in contrast with diamagnetic CdTe with its dominating orbital
      quantization. The mechanisms can be identified by the distinct magnetic field
      dependence of the SHG intensity which scales with the spin splitting in the
      paramagnetic case as compared to the H2 dependence observed for the diamagnetic
      case.

PMID- 16605868
TI  - Efficient single-photon sources based on low-density quantum dots in photonic
      crystal nanocavities.
AB  - An efficient single-photon source based on low-density InGaAs quantum dots in a
      photonic-crystal nanocavity is demonstrated. The single-photon source features
      the effects of a photonic band gap, yielding a single-mode spontaneous emission
      coupling efficiency as high as beta = 92% and a linear polarization degree up to
      p = 95%. This appealing performance makes it well suited for practical
      implementation of polarization-encoded schemes in quantum cryptography.

PMID- 16605869
TI  - Terahertz radiation by an ultrafast spontaneous polarization modulation of
      multiferroic BiFeO3 thin films.
AB  - Terahertz (THz) radiation has been observed from multiferroic BiFeO3 thin films
      via ultrafast modulation of spontaneous polarization upon carrier excitation with
      illumination of femtosecond laser pulses. The radiated THz pulses from BiFeO3
      thin films were clarified to directly reflect the spontaneous polarization state,
      giving rise to a memory effect in a unique style and enabling THz radiation even
      at zero-bias electric field. On the basis of our findings, we demonstrate
      potential approaches to ferroelectric nonvolatile random access memory with
      nondestructive readability and ferroelectric domain imaging microscopy using THz
      radiation as a sensitive probe.

PMID- 16605870
TI  - Influence of copolymer interface orientation on the optical emission of polymeric
      semiconductor heterojunctions.
AB  - We have examined the Coulombic interactions at the interface in a blend of two
      copolymers with intramolecular charge-transfer character and optimized band
      offsets for photoinduced charge generation. The combination of both time-resolved
      measurements of photoluminescence, and quantum-chemical modeling of the
      heterojunction allows us to show that relative orientation across the
      heterojunction can lead to either a repulsive barrier ( approximately 65 meV) or
      an attractive interaction which can enhance the charge-transfer processes. We
      conclude that polymer orientation at the heterojunction can be as important as
      energy-band offsets in determining the dynamics of charge separation and optical
      emission.

PMID- 16605871
TI  - Polarization dependence of L- and M-edge resonant inelastic X-ray scattering in
      transition-metal compounds.
AB  - The resonant inelastic x-ray scattering (RIXS) cross section at the L and M edges
      of transition-metal compounds is studied using an effective scattering operator.
      The intensities of the elastic peak and for spin-flip processes are derived. It
      is shown how the polarization dependence can be used to select transitions.
      Comparisons are made with experiment. A detailed analysis of the polarization and
      angular dependence of L- and M-edge RIXS for divalent copper compounds, such as
      the high-Tc superconductors, is given.

PMID- 16605872
TI  - Observation of electron gas cooling in free sodium clusters.
AB  - Free size-selected Na+(n) (n = 16-250) clusters have been studied by femtosecond
      pump-probe photoelectron and photofragmentation spectroscopy. Thermal electron
      emission from the hot electron gas was used to monitor the energy transfer from
      the electronic system to lattice vibrations. The electron-phonon coupling
      constants determined for the different sizes can be described by the radius
      dependent function g(R) = (2.3 + 114 A2/R2) X 10(16) W/m3K. No strong quantum
      size effect was observed even for the smallest cluster size.

PMID- 16605873
TI  - Core precession and global modes in granular bulk flow.
AB  - We report a novel transition to core precession for granular flows in a split
      bottomed shear cell. This transition is related to a qualitative change in the 3D
      flow structure: For shallow layers of granular material, the shear zones
      emanating from the split reach the free surface, while for deep layers the shear
      zones meet below the surface, causing precession. The surface velocities reflect
      this transition by a change of symmetry. As a function of layer depth, we find
      that three qualitatively different smooth and robust granular flows can be
      created in this simple shearing geometry.

PMID- 16605874
TI  - Brownian forces in sheared granular matter.
AB  - We present results from a series of experiments on a granular medium sheared in a
      Couette geometry and show that their statistical properties can be computed in a
      quantitative way from the assumption that the resultant from the set of forces
      acting in the system performs a Brownian motion. The same assumption has been
      utilized, with success, to describe other phenomena, such as the Barkhausen
      effect in ferromagnets, and so the scheme suggests itself as a more general
      description of a wider class of driven instabilities.

PMID- 16605875
TI  - Hydrodynamic damping of membrane thermal fluctuations near surfaces imaged by
      fluorescence interference microscopy.
AB  - Hydrodynamic coupling between closely apposed lipid bilayer membranes can
      substantially slow the time scale of thermal fluctuations. These effects could
      dominate the kinetics of macromolecular interactions at membrane interfaces, and
      may exert important influences over the interactions between living cells. Here,
      we study a reconstituted membrane system consisting of two planar bilayers with
      average separation distances of 30-60 nm. This spacing range is comparable to
      that of natural intercellular junctions. Using real-time fluorescence
      interference contrast imaging, spatial and temporal characteristics of the
      thermal fluctuation spectra are monitored simultaneously. Strong hydrodynamic
      damping of the fluctuation time scale is observed whereas fluctuation spatial
      dimensions are unaltered by proximity to another surface. These observations
      provide experimental confirmation of recent theoretical models.

PMID- 16605876
TI  - Single molecule unzipping of coiled coils: sequence resolved stability profiles.
AB  - We use a high resolution atomic force microscopy technique to mechanically unzip
      and rezip single coiled-coil proteins. This allows us to read off the complete
      stability profile of the protein turn by turn. We investigated three coiled coils
      with different length as well as a point mutation and find force fluctuations
      between 9 and 15 pN that can be directly related to the amino-acid sequences. An
      equilibrium model previously applied to DNA fully describes the mechanical
      unzipping process including free-energy contributions of the individual turns and
      seed formation energy.

PMID- 16605877
TI  - Dynamics of polymer translocation through nanopores: theory meets experiment.
AB  - The dynamics of translocation of polymer molecules through nanopores is
      investigated via molecular dynamics. We find that an off-lattice minimalist model
      of the system is sufficient to reproduce quantitatively all the experimentally
      observed trends and scaling behavior. Specifically, simulations show (i) two
      translocation regimes depending on the ratio of pore and polymer length, (ii) two
      different regimes for the probability of translocation depending on applied
      voltage, (iii) an exponential dependence of translocation velocity upon applied
      voltage, and (iv) an exponential decrease of the translocation time with
      temperature. We also propose a simple theoretical explanation of each of the
      observed trends within a free energy landscape framework.

PMID- 16605878
TI  - Microrheology probes length scale dependent rheology.
AB  - We exploit the power of microrheology to measure the viscoelasticity of entangled
      F-actin solutions at different length scales from 1 to 100 microm over a wide
      frequency range. We compare the behavior of single probe-particle motion to that
      of the correlated motion of two particles. By varying the average length of the
      filaments, we identify fluctuations that dissipate diffusively over the filament
      length. These provide an important relaxation mechanism of the elasticity between
      0.1 and 30 rad/sec.

PMID- 16605879
TI  - Condensation transition in DNA-polyaminoamide dendrimer fibers studied using
      optical tweezers.
AB  - When mixed together, DNA and polyaminoamide dendrimers form fibers that condense
      into a compact structure. We use optical tweezers to pull condensed fibers and
      investigate the decondensation transition by measuring force-extension curves
      (FECs). A characteristic force plateau (around 10 pN) and hysteresis between the
      pulling and relaxation cycles are observed for different dendrimer sizes,
      indicating the existence of a first-order transition between two phases
      (condensed and extended) of the fiber. Upon salt variation FECs change noticeably
      confirming that electrostatic forces drive the condensation transition. We
      propose a simple model for the decondensing transition that qualitatively
      reproduces the FECs and which is confirmed by atomic force microscopy images.

PMID- 16605880
TI  - Overembedding method for modeling nonstationary systems.
AB  - We propose a general overembedding method for modeling and prediction of
      nonstationary systems. It basically enlarges the standard time-delay-embedding
      space by inclusion of the (unknown) slow driving signal, which is estimated
      simultaneously with the intrinsic stationary dynamics. Our method can be
      implemented with any modeling tool. Using, in particular, artificial neural
      networks, its application to both synthetic and real-world time series shows that
      it is highly efficient, leading to much more accurate results and longer
      prediction horizons than other existing overembedding methods in the literature.

PMID- 16605881
TI  - Comment on "Destructive effect of disorder and bias voltage on interface
      resonance transmission in symmetric tunnel junctions".

PMID- 16605883
TI  - Comment on "Multiple bosonic mode coupling in the electron self-energy of (La(2
      x)Srx)CuO4".

PMID- 16605885
TI  - Wang-Landau algorithm for continuous models and joint density of states.
AB  - We present a modified Wang-Landau algorithm for models with continuous degrees of
      freedom. We demonstrate this algorithm with the calculation of the joint density
      of states of ferromagnet Heisenberg models and a model polymer chain. The joint
      density of states contains more information than the density of states of a
      single variable-energy, but is also much more time consuming to calculate. We
      present strategies to significantly speed up this calculation for large systems
      over a large range of energy and order parameter.

PMID- 16605886
TI  - Spontaneous-emission rate in microcavities: application to two-dimensional
      photonic crystals.
AB  - We present a simple, efficient procedure to compute the spontaneous-emission rate
      from short-time finite-difference time-domain (FDTD) data of the electromagnetic
      field energy in microcavities of arbitrary geometry. As an illustration, we apply
      this procedure to two-dimensional photonic crystals. For comparison, we calculate
      the local radiative density of states employing an unconditionally stable FDTD
      method, that is without solving the eigenvalue problem and integrating over the
      (first) Brillouin zone. We demonstrate that both methods yield the same
      predictions about the enhancement or suppression of the spontaneous-emission rate
      by photonic crystals.

PMID- 16605887
TI  - Definition and relevance of nonequilibrium intensive thermodynamic parameters.
AB  - We show that intensive thermodynamic parameters associated to additive conserved
      quantities can be naturally defined from a statistical approach in far-from
      equilibrium steady-state systems, under few assumptions, and without any detailed
      balance requirement. It may apply, e.g., to dissipative systems such as granular
      gases where volume or mass is still conserved or to systems with periodic
      boundary conditions where fluxes of conserved quantities are present. We
      emphasize the usefulness of this concept to characterize the coexistence of
      different nonequilibrium phases and discuss the influence of the contact between
      two different systems, in relation with measurement issues.

PMID- 16605888
TI  - Statistical mechanical derivation of Jarzynski's identity for thermostated non
      Hamiltonian dynamics.
AB  - The recent Jarzynski identity (JI) relates thermodynamic free energy differences
      to nonequilibrium work averages. Several proofs of the JI have been provided on
      the thermodynamic level. They rely on assumptions such as equivalence of
      ensembles in the thermodynamic limit or weakly coupled infinite heat baths.
      However, the JI is widely applied to computer simulations involving finite
      numbers of particles, whose equations of motion are strongly coupled to a few
      extra degrees of freedom modeling a thermostat. In this case, the above
      assumptions are no longer valid. We propose a statistical mechanical approach to
      the JI solely based on the specific equations of motion, without any further
      assumption. We provide a detailed derivation for the non-Hamiltonian Nose-Hoover
      dynamics, which is routinely used in computer simulations to produce canonical
      sampling.

PMID- 16605889
TI  - Direct evaluation of large-deviation functions.
AB  - We introduce a numerical procedure to evaluate directly the probabilities of
      large deviations of physical quantities, such as current or density, that are
      local in time. The large-deviation functions are given in terms of the typical
      properties of a modified dynamics, and since they no longer involve rare events,
      can be evaluated efficiently and over a wider ranges of values. We illustrate the
      method with the current fluctuations of the Totally Asymmetric Exclusion Process
      and with the work distribution of a driven Lorentz gas.

PMID- 16605890
TI  - Microfabricated quadrupole ion trap for mass spectrometer applications.
AB  - An array of miniaturized cylindrical quadrupole ion traps, with a radius of 20
      microm, is fabricated using silicon micromachining using phosphorus doped
      polysilicon and silicon dioxide for the purpose of creating a mass spectrometer
      on a chip. We have operated the array for mass-selective ion ejection and mass
      analysis using Xe ions at a pressure of 10(-4). The scaling rules for the ion
      trap in relation to operating pressure, voltage, and frequency are examined.

PMID- 16605891
TI  - Accurate evolution of orbiting binary black holes.
AB  - We present a detailed analysis of binary black hole evolutions in the last orbit
      and demonstrate consistent and convergent results for the trajectories of the
      individual bodies. The gauge choice can significantly affect the overall accuracy
      of the evolution. It is possible to reconcile certain gauge-dependent
      discrepancies by examining the convergence limit. We illustrate these results
      using an initial data set recently evolved by Brugmann et al. [Phys. Rev. Lett.
      92, 211101 (2004)10.1103/PhysRevLett.92.211101]. For our highest resolution and
      most accurate gauge, we estimate the duration of this data set's last orbit to be
      approximately 59MADM.

PMID- 16605892
TI  - Nonequilibrium thermodynamics of spacetime.
AB  - It has previously been shown that the Einstein equation can be derived from the
      requirement that the Clausius relation dS=deltaQ/T hold for all local
      acceleration horizons through each spacetime point, where is one-quarter the
      horizon area change in Planck units and deltaQ and T are the energy flux across
      the horizon and the Unruh temperature seen by an accelerating observer just
      inside the horizon. Here we show that a curvature correction to the entropy that
      is polynomial in the Ricci scalar requires a nonequilibrium treatment. The
      corresponding field equation is derived from the entropy balance relation
      dS=deltaQ/T+diS, where diS is a bulk viscosity entropy production term that we
      determine by imposing energy-momentum conservation. Entropy production can also
      be included in pure Einstein theory by allowing for shear viscosity of the
      horizon.

PMID- 16605893
TI  - Temperature of the inflaton and duration of inflation from Wilkinson microwave
      anisotropy probe data.
AB  - If the initial state of the inflaton field is taken to have a thermal
      distribution instead of the conventional zero particle vacuum state then the
      curvature power spectrum gets modified by a temperature dependent factor such
      that the fluctuation spectrum of the microwave background radiation is enhanced
      at larger angles. We compare this modified cosmic microwave background spectrum
      with Wilkinson microwave anisotropy probe data to obtain an upper bound on the
      temperature of the inflaton at the time our current horizon crossed the horizon
      during inflation. We further conclude that there must be additional -foldings of
      inflation beyond what is needed to solve the horizon problem.

PMID- 16605894
TI  - Parity doubling and SU(2)LxSU(2)R restoration in the hadron spectrum.
AB  - We construct the most general nonlinear representation of chiral SU(2)LxSU(2)R
      broken down spontaneously to the isospin SU(2), on a pair of hadrons of same spin
      and isospin and opposite parity. We show that any such representation is
      equivalent, through a hadron field transformation, to two irreducible
      representations on two hadrons of opposite parity with different masses and axial
      vector couplings. This implies that chiral symmetry realized in the Nambu
      Goldstone mode does not predict the existence of degenerate multiplets of hadrons
      of opposite parity nor any relations between their couplings or masses.

PMID- 16605895
TI  - Supersymmetric standard model from the heterotic string.
AB  - We present a [FORMULA: SEE TEXT] orbifold compactification of the E8xE8 heterotic
      string which leads to the (supersymmetric) standard model gauge group and matter
      content. The quarks and leptons appear as three 16-plets of SO(10), whereas the
      Higgs fields do not form complete SO(10) multiplets. The model has large vacuum
      degeneracy. For generic vacua, no exotic states appear at low energies and the
      model is consistent with gauge coupling unification. The top quark Yukawa
      coupling arises from gauge interactions and is of the order of the gauge
      couplings, whereas the other Yukawa couplings are suppressed.

PMID- 16605897
TI  - Distinguishing between Dirac and Majorana neutrinos with two-particle
      interferometry.
AB  - Two-particle interferometry, a second-order interference effect, is explored as
      another possible tool to distinguish between massive Dirac and Majorana
      neutrinos. A simple theoretical framework is discussed in the context of several
      gedanken experiments. The method can in principle provide both the mass scale and
      the quantum nature of the neutrino for a certain class of incoherent left-handed
      source currents.

PMID- 16605896
TI  - Experimental limits on weak annihilation contributions to decays.
AB  - We present the first experimental limits on high-q2 contributions to charmless
      semileptonic decays of the form expected from the weak annihilation (WA) decay
      mechanism. Such contributions could bias determinations of /Vub/ from inclusive
      measurements of B-->Xulupsilon. Using a wide range of models based on available
      theoretical input we set a limit of GammaWA/Gammab-->u<7.4% (90% confidence
      level) on the WA fraction, and assess the impact on previous inclusive
      determinations of /Vub/.

PMID- 16605899
TI  - Stabilization of nuclear isovector valence-shell excitations.
AB  - Excited states in 138Ce have been studied via the 12C(138Ce, 138Ce*) Coulomb
      excitation reaction at 480 MeV. Relative cross sections have been determined from
      the gamma-ray yields observed with Gammasphere. The E2 and M1 strength
      distributions between the lowest six 2+ states up to 2.7 MeV enables us to
      identify the 2(4)+ state in 138Ce as the dominant fragment of the one-phonon
      2(1,ms)+ mixed-symmetry state. Mixing between this level and a nearby isoscalar
      state is observed and is more than 4 times larger than in the neighboring isotone
      136Ba. This is direct evidence that the stability of mixed-symmetry states
      strongly depends on the underlying subshell structure.

PMID- 16605900
TI  - Electrodynamic trapping of spinless neutral atoms with an atom chip.
AB  - Three-dimensional electrodynamic trapping of neutral atoms has been demonstrated.
      By applying time-varying inhomogeneous electric fields with micron-sized
      electrodes, nearly 10(2) strontium atoms in the 1S0 state have been trapped with
      a lifetime of 80 ms. In order to design the electrodes, we numerically analyzed
      the electric field and simulated atomic trajectories in the trap, which showed
      reasonable agreement with the experiment.

PMID- 16605901
TI  - Threshold electron-impact ionization mechanism for hydrogen atoms.
AB  - The near-threshold evolution of electron-impact ionization of hydrogen is
      revealed with measurements of the angular and energy correlations of the outgoing
      electrons down to 0.05 eV. The single-, double-, and triple-differential cross
      sections in the perpendicular plane are measured simultaneously using a dual
      wedge-and-strip detector on a single-toroidal energy analyzer, avoiding many
      experimental problems. The experimental and calculated data are in excellent
      agreement, within the experimental precision of +/-10%, and provide further
      evidence that the accurate solution of the Schrodinger equation provides a
      complete description of the reaction dynamics of near-threshold ionization.

PMID- 16605902
TI  - Controlling collisions of ultracold atoms with dc electric fields.
AB  - It is demonstrated that elastic collisions of ultracold atoms forming a
      heteronuclear collision complex can be manipulated by laboratory practicable dc
      electric fields. The mechanism of electric field control is based on the
      interaction of the instantaneous dipole moment of the collision pair with
      external electric fields. It is shown that this interaction is dramatically
      enhanced in the presence of a p-wave shape or Feshbach scattering resonance near
      the collision threshold, which leads to novel electric-field-induced Feshbach
      resonances.

PMID- 16605903
TI  - Nonlinear resonance absorption in the laser-cluster interaction.
AB  - Rare-gas or metal clusters are known to absorb laser energy very efficiently.
      Upon cluster expansion, the Mie plasma frequency may become equal to the laser
      frequency. This linear resonance has been well studied both experimentally and
      theoretically employing pump probe schemes. In this work, we focus on the few
      cycle regime or the early stage of the cluster dynamics, where linear resonance
      is not met but, nevertheless, efficient absorption of laser energy persists. By
      retrieving time-dependent oscillator frequencies from particle-in-cell simulation
      results, we show that nonlinear resonance is the dominant mechanism behind outer
      ionization and energy absorption in near infrared laser-driven clusters.

PMID- 16605904
TI  - Experimental realization of an on-chip all-optical analogue to
      electromagnetically induced transparency.
AB  - We provide the first experimental observation of structure tuning of the
      electromagnetically induced transparency-like spectrum in integrated on-chip
      optical resonator systems. The system consists of coupled silicon ring resonators
      with 10 microm diameter on silicon, where the coherent interference between the
      two coupled resonators is tuned. We measured a transparency-resonance mode with a
      quality factor of 11,800.

PMID- 16605905
TI  - Two level metal vapor lasers with thermal creation of population inversion.
AB  - We present a new technique for direct conversion of thermal energy into coherent
      radiation. The near-surface layer of evaporated excited atoms of rare earth
      metals is proposed to be used as a converter. There is an inverted population in
      this layer. Operation principles of two level lasers on the transitions to the
      ground state using Eu are considered. The fact of detachment of Sm atoms in the
      excited 4f(N-1)5d6s2 state during the thermal evaporation process has been proved
      experimentally.

PMID- 16605906
TI  - Coherent thermal antenna using a photonic crystal slab.
AB  - We show that a photonic crystal film can emit coherent thermal radiation. We
      demonstrate the key role of leaky waves existing at the air-photonic crystal
      interface. The frequency and direction of emission depend on the lattice
      parameters. This paves the way towards the design of coherent infrared antennas.

PMID- 16605907
TI  - Spectral redshift in harmonic generation from plasma dynamics in the laser focus.
AB  - High-precision spectral measurements on the 9th harmonic generated in xenon gas
      are compared with calculations of the plasma dynamics resulting from multiphoton
      ionization in the laser focus. For the regime of 300 ps pulses and above
      saturation intensities a novel mechanism producing redshifts in the harmonics is
      uncovered and explained. Ions play a double role: the nonlinear susceptibility of
      the ions is decisive for the harmonic intensity, while their mutual repulsion and
      the associated increase of the index of refraction is identified as the cause of
      the redshift.

PMID- 16605908
TI  - Synchronization of oscillating reactions in an extended fluid system.
AB  - We present experiments on the synchronization of a dynamical, chemical process in
      an extended, flowing, fluid system. The oscillatory Belousov-Zhabotinsky chemical
      reaction is the process studied, and the flow is an annular chain of
      counterrotating vortices. Azimuthal motion of the vortices is controlled
      externally, enabling us to vary the type of transport. We find that oscillations
      of the Belousov-Zhabotinsky reaction synchronize throughout the extended fluid
      system only if transport in the flow is superdiffusive, with tracers in the flow
      undergoing rapid, distant jumps called Levy flights.

PMID- 16605909
TI  - Singular jets and bubbles in drop impact.
AB  - We show that when water droplets gently impact on a hydrophobic surface, the
      droplet shoots out a violent jet, the velocity of which can be up to 40 times the
      drop impact speed. As a function of the impact velocity, two different
      hydrodynamic singularities are found that correspond to the collapse of the air
      cavity formed by the deformation of the drop at impact. It is the collapse that
      subsequently leads to the jet formation. We show that the divergence of the jet
      velocity can be understood using simple scaling arguments. In addition, we find
      that very large air bubbles can remain trapped in the drops. The surprising
      occurrence of the bubbles for low-speed impact is connected with the nature of
      the singularities, and can have important consequences for drop deposition, e.g.,
      in ink-jet printing.

PMID- 16605910
TI  - Properties of steady states in turbulent axisymmetric flows.
AB  - We experimentally study the properties of mean and most probable velocity fields
      in a turbulent von Karman flow. These fields are found to be described by two
      families of functions, as predicted by a recent statistical mechanics study of 3D
      axisymmetric flows. We show that these functions depend on the viscosity and on
      the forcing. Furthermore, when the Reynolds number is increased, we exhibit a
      tendency for Beltramization of the flow, i.e., a velocity-vorticity alignment.
      This result provides a first experimental evidence of nonlinearity depletion in
      nonhomogeneous nonisotropic turbulent flow.

PMID- 16605911
TI  - Chaotic advection and targeted mixing.
AB  - The advection of passive tracers in an oscillating vortex chain is investigated.
      It is shown that by adding a suitable perturbation to the ideal flow, the induced
      chaotic advection exhibits two remarkable properties which do not hold in the
      case of a generic perturbation: Particles remain trapped within a specific domain
      bounded by two oscillating barriers (suppression of chaotic transport along the
      channel), and the stochastic sea seems to cover this whole bounded domain
      (enhancement of mixing within the rolls).

PMID- 16605912
TI  - Bubbling in unbounded coflowing liquids.
AB  - An investigation of the stability of low density and viscosity fluid jets and
      spouts in unbounded coflowing liquids is presented. A full parametrical analysis
      from low to high Weber and Reynolds numbers shows that the presence of any fluid
      of finite density and viscosity inside the hollow jet elicits a transition from
      an absolute to a convective instability at a finite value of the Weber number,
      for any value of the Reynolds number. Below that critical value of the Weber
      number, the absolute character of the instability leads to local breakup, and
      consequently to local bubbling. Experimental data support our model.

PMID- 16605913
TI  - Superradiant spin-flip radiative emission of a spin-polarized free-electron beam.
AB  - Radiative emission from the magnetic moments of the spins of an electron beam has
      never been observed directly, because it is fundamentally much weaker than the
      electric charge emission. We show that the detectivity of spin-flip and combined
      spin-flip-cyclotron-resonance-emission radiation can be substantially enhanced by
      operating with ultrashort spin-polarized electron beam bunches under conditions
      of superradiant (coherent) emission. The proposed superradiant spin-flip
      radiative emission scheme can be used for noninvasive diagnostics of polarized
      electron or positron beams. Such beams are of relevance in important scattering
      experiments off nucleons in nuclear physics and off magnetic targets in condensed
      matter physics.

PMID- 16605914
TI  - Heating of ions by Alfven waves via nonresonant interactions.
AB  - Finite-amplitude intrinsic Alfven waves exist pervasively in astrophysical and
      solar-terrestrial environment. It is generally believed that linear wave-particle
      resonant interaction between thermal protons and Alfven waves is ineffective when
      the proton beta is low. However, this Letter demonstrates that the ions can be
      heated by Alfven waves via nonresonant nonlinear interaction. Contrary to the
      customary expectation, it is found that the lower the plasma beta value, the more
      effective is the heating process. It is also shown that the ion temperature
      increase is more prominent along perpendicular direction.

PMID- 16605915
TI  - Study of ultraintense laser-produced fast-electron propagation and filamentation
      in insulator and metal foil targets by optical emission diagnostics.
AB  - The transport of an intense electron beam produced by ultrahigh intensity laser
      pulses through metals and insulators has been studied by high resolution imaging
      of the optical emission from the targets. In metals, the emission is mainly due
      to coherent transition radiation, while in plastic, it is due to the Cerenkov
      effect and it is orders of magnitude larger. It is also observed that in the case
      of insulators the fast-electron beam undergoes strong filamentation and the
      number of filaments increases with the target thickness. This filamented behavior
      in insulators is due to the instability of the ionization front related to the
      electric field ionization process. The filamentary structures characteristic
      growth rate and characteristic transversal scale are in agreement with analytical
      predictions.

PMID- 16605916
TI  - A modified fermi model for wave-particle interactions in plasmas.
AB  - Wave-particle interactions in plasmas are investigated through a nonlinear map
      that describes elastic collisions between an ensemble of particles and two
      barriers. The amplitude of the barriers, proportional to the energy of the wave,
      can increase or decrease due to the sequence of stochastic collisions. After an
      initial exponential decrease, the nonlinear strong trapping regime is
      characterized by low-frequency oscillations of the amplitude of the barriers
      around a certain saturation value. This is a transitory phenomenon stemming from
      the dynamical approach towards equilibrium in the wave-particle conservative
      system.

PMID- 16605898
TI  - Measurement of the inclusive jet cross section using the kT algorithm in pp
      collisions at (square root s)=1.96 TeV.
AB  - We report on a measurement of the inclusive jet production cross section as a
      function of the jet transverse momentum in pp collisions at (square root s)=1.96
      TeV using data collected with the upgraded Collider Detector at Fermilab in run
      II, corresponding to an integrated luminosity of 385 pb-1. The measurement is
      carried out for jets with rapidity 0.1</yjet/<0.7 and transverse momentum in the
      range 54<pjetT<700 GeV/c. Next-to-leading order perturbative QCD predictions are
      in good agreement with the measured cross section after the necessary
      nonperturbative parton-to-hadron corrections are included.

PMID- 16605917
TI  - Coherent wake emission of high-order harmonics from overdense plasmas.
AB  - We present a new mechanism for high-order harmonic generation by reflection of a
      laser beam from an overdense plasma, efficient even at moderate laser intensities
      (down to Igamma2 approximately 4x10(15) W cm-2 microm2). In this mechanism, a
      transient phase matching between the electromagnetic field and plasma
      oscillations within a density gradient leads to the emission of harmonics up to
      the plasma frequency. These plasma oscillations are periodically excited in the
      wake of attosecond electron bunches which sweep across the density gradient. This
      process leads to a train of unevenly spaced chirped attosecond pulses and, hence,
      to broadened and chirped harmonics. This last effect is confirmed experimentally.

PMID- 16605918
TI  - Spontaneous formation of closed-field torus equilibrium via current jump observed
      in an electron-cyclotron-heated plasma.
AB  - Spontaneous current jump resulting in the formation of closed field equilibrium
      has been observed in electron-cyclotron-heated toroidal plasmas under steady
      external fields composed of a toroidal field and a relatively weak vertical field
      in the low aspect ratio torus experiment device. This bridges the gap between the
      open field equilibrium maintained by a pressure-driven current in the external
      field and the closed field equilibrium at a larger current. Experimental results
      and theoretical analyses suggest a current jump model that is based on the
      asymmetric electron confinement along the field line appearing upon simultaneous
      transitions of field topology and equilibrium.

PMID- 16605920
TI  - Start-up scenario in gyrotrons with a nonstationary microwave-field structure.
AB  - Megawatt class gyrotrons operate in very high-order modes. Therefore, control of
      a gyrotron oscillator's start-up is important for excitation of the desired mode
      in the presence of the many undesired modes. Analysis of such scenario using the
      self-consistent code MAGY [M. Botton, IEEE Trans. Plasma Sci. 26, 882
      (1998)10.1109/27.700860] reveals that during start-up not only mode amplitudes
      vary in time, but also their axial structure can be time dependent. Simulations
      done for a 1.5 MW gyrotron show that the excitation of a single operating mode
      can exhibit a sort of intermittency when, first, it is excited as a mode whose
      axial structure extends outside the interaction cavity, then it ceases and then
      reappears as a mode mostly localized in the cavity. This phenomenon makes it
      necessary to analyze start-up scenarios in such gyrotrons with the use of codes
      that account for the possible evolution of field profiles.

PMID- 16605921
TI  - Surface specific heat of 3He and Andreev bound states.
AB  - High resolution measurements of the specific heat of liquid 3He in the presence
      of a silver surface have been performed at temperatures near the superfluid
      transition in the pressure range of 1-29 bar. The surface contribution to the
      heat capacity is identified with Andreev bound states of quasiparticles that have
      a range of half a coherence length.

PMID- 16605919
TI  - Slow transition of energy transport in high-temperature plasmas.
AB  - A new slow transition process for energy transport in magnetically confined
      plasmas is reported. The slow transition is characterized by the change between
      two metastable transport conditions characterized by a weak and a strong electron
      temperature (Te) dependence of normalized heat flux. These two branches are found
      to merge at the critical gradient. In metastable transport, the derivative of
      normalized heat flux to the Te gradient, [EQUATION: SEE TEXT], is positive, while
      it becomes negative during the transition phase. The time for the transition
      increases as the normalized Te gradient is increased and exceeds the transport
      time scale characterized by the global energy confinement time.

PMID- 16605922
TI  - Formation of a new dynamical mode in -uranium observed by inelastic x-ray and
      neutron scattering.
AB  - Phonon dispersion curves were obtained from inelastic x-ray and neutron
      scattering measurements on alpha-uranium single crystals at temperatures from 298
      to 573 K. Both measurements showed a softening and an abrupt loss of intensity in
      the longitudinal optic branch along [00zeta] above 450 K. Above the same
      temperature a new dynamical mode of comparable intensity emerges along the
      [01zeta] zone boundary with energy near the top of the phonon spectrum. The new
      mode forms without a structural transition but coincides with an anomaly in the
      mechanical deformation behavior. We argue that the mode is an intrinsically
      localized vibration and formed as a result of a strong electron-phonon
      interaction.

PMID- 16605923
TI  - Interplay between structure and magnetism in Mo12S9I9 nanowires.
AB  - We investigate the equilibrium geometry and electronic structure of Mo12S9I9
      nanowires using ab initio density functional calculations. The skeleton of these
      unusually stable nanowires consists of rigid, functionalized Mo octahedra,
      connected by flexible, bistable sulfur bridges. This structural flexibility
      translates into a capability to stretch up to approximately 20% at almost no
      energy cost. The nanowires change from conductors to narrow-gap magnetic
      semiconductors in one of their structural isomers.

PMID- 16605924
TI  - Dislocation patterns and the similitude principle: 2.5D mesoscale simulations.
AB  - During plastic flow of crystalline solids, dislocations self-organize in the form
      of patterns, with a wavelength that is inversely proportional to stress. After
      four decades of investigations, the origin of this property is still under
      discussion. We show that dislocation patterns verifying the principle of
      similitude can be obtained from dynamics simulations of double slip. These
      patterns are formed in the presence of long- and short-range interactions, but
      they are not significantly modified when only short-range interactions are
      present. This new insight into dislocation patterning phenomena has important
      implications regarding current models.

PMID- 16605925
TI  - Real-time observation of structural and orientational transitions during growth
      of organic thin films.
AB  - We study kinetically controlled orientational and structural transitions of
      molecular thin films during growth in situ and in real time, using
      diindenoperylene (DIP) as an example. By time-resolved surface-sensitive x-ray
      scattering (out of plane and in plane), we follow the organic molecular beam
      deposition of DIP on silicon oxide, on stepped sapphire, and on rubrene as an
      organic model surface. We identify transitions for the few-monolayer (ML) regime,
      as well as for thick (several 10's of ML) films. We show that the differences in
      the interaction of DIP with the substrate change the thickness as well as
      temperature range of the transitions, which include (transient) strain, subtle
      changes of the orientation, as well as complete reorientation. These effects
      should be considered rather general features of the growth of organics, which,
      with its orientational degrees of freedom, is qualitatively different from growth
      of inorganics.

PMID- 16605926
TI  - Evidence for p-type doping of InN.
AB  - The first evidence of successful p-type doping of InN is presented. It is shown
      that InN:Mg films consist of a p-type bulk region with a thin n-type inversion
      layer at the surface that prevents electrical contact to the bulk. Capacitance
      voltage measurements indicate a net concentration of ionized acceptors below the 
      type surface. Irradiation with 2 MeV He+ ions is used to convert the bulk of
      InN:Mg from p to n-type, at which point photoluminescence is recovered. The
      conversion is well explained by a model assuming two parallel conducting layers
      (the surface and the bulk) in the films.

PMID- 16605927
TI  - Changes in the Burgers vector of perfect dislocation loops without contact with
      the external dislocations.
AB  - We report the observations of a new type of changing process in the Burgers
      vector of dislocations by in situ transmission electron microscopy. Small
      interstitial-type perfect dislocation loops in bcc iron with diameters less than
      approximately 50 nm are transformed from a 1/2<111> loop to another 1/2<111> one
      or an energetically unfavorable <100> one; furthermore, a <100> loop is
      transformed to a 1/2<111> one. These transformations occurred on high-energy
      electron irradiation or simple heating without contact with external
      dislocations. The origin of these phenomena is discussed.

PMID- 16605928
TI  - Quantum nature of the sign preference in ion-induced nucleation.
AB  - Observed first in Wilson's pioneering experiments in the cloud chamber, the sign
      preference has remained a mystery for more than a century. We investigate the
      sign preference using a quantum approach and show that this puzzling phenomenon
      is essentially quantum in nature. It is shown that the effect of the chemical
      identity of the core ion is controlled by the electronic structure of the core
      ion through the influence on the intermolecular bonding energies during the
      initial steps of cluster formation. Our results demonstrate the superiority of
      the quantum approach and indicate fundamental problems of conventional ion
      induced nucleation theories, in which the electronic structure of the core ion is
      either ignored or not treated rigorously.

PMID- 16605929
TI  - Orientation dependence of strained-Ge surface energies near (001): role of dimer
      vacancy lines and their interactions with steps.
AB  - Recent experiments and calculations have highlighted the important role of
      surface-energy (gamma) anisotropy in governing island formation in the Ge/Si(001)
      system. To further elucidate the factors determining this anisotropy, we perform
      atomistic and continuum calculations of the orientation dependence of gamma for
      strained-Ge surfaces near (001), accounting for the presence of dimer-vacancy
      lines (DVLs). The net effect of DVLs is found to be a substantial reduction in
      the magnitude of the slope of gamma vs orientation angle, relative to the highly
      negative value derived for non-DVL, dimer-reconstructed, strained-Ge(001)
      surfaces. The present results thus point to an important role of DVLs in
      stabilizing the (001) surface orientation of a strained-Ge wetting layer.

PMID- 16605930
TI  - Experimental determination of the helium-metal interaction potential by
      interferometry of nanostructured surfaces.
AB  - We present a direct experimental comparison of the helium-surface interaction
      potential for two unreconstructed metal surfaces. We analyze phase shifts in
      helium atom scattering from a nanostructured bimetallic surface to yield the
      relative shape and position of an adsorbate's potential with respect to the
      reference defined by the substrate. In our prototype system, submonolayer growth
      of Ni on Cu(100), the He-Ni/Cu(100) potential has an attractive well that is
      1.6+/-0.4 meV shallower, and a repulsive wall 0.11+/-0.03 A closer to the ion
      cores, compared to the He-Cu(100) potential. Our observations provide a ready
      test of state-of-the-art theoretical calculations.

PMID- 16605931
TI  - Observation of a Mott insulating ground state for Sn/Ge(111) at low temperature.
AB  - We report an investigation on the properties of 0.33 ML of Sn on Ge(111) at
      temperatures down to 5 K. Low-energy electron diffraction and scanning tunneling
      microscopy show that the (3x3) phase formed at approximately 200 K, reverts to a
      new ((square root 3)x(square root 3))R30 degrees phase below 30 K. The vertical
      distortion characteristic of the (3x3) phase is lost across the phase transition,
      which is fully reversible. Angle-resolved photoemission experiments show that,
      concomitantly with the structural phase transition, a metal-insulator phase
      transition takes place. The ((square root 3)x(square root 3))R30 degrees ground
      state is interpreted as the formation of a Mott insulator for a narrow half
      filled band in a two-dimensional triangular lattice.

PMID- 16605932
TI  - Excitons in boron nitride nanotubes: dimensionality effects.
AB  - We show that the optical absorption spectra of boron nitride (BN) nanotubes are
      dominated by strongly bound excitons. Our first-principles calculations indicate
      that the binding energy for the first and dominant excitonic peak depends
      sensitively on the dimensionality of the system, varying from 0.7 eV in bulk
      hexagonal BN via 2.1 eV in the single sheet of BN to more than 3 eV in the
      hypothetical (2, 2) tube. The strongly localized nature of this exciton dictates
      the fast convergence of its binding energy with increasing tube diameter towards
      the sheet value. The absolute position of the first excitonic peak is almost
      independent of the tube radius and system dimensionality. This provides an
      explanation for the observed "optical gap" constancy for different tubes and bulk
      hexagonal BN.

PMID- 16605933
TI  - Excitons and many-electron effects in the optical response of single-walled boron
      nitride nanotubes.
AB  - We report first-principles calculations of the effects of quasiparticle self
      energy and electron-hole interaction on the optical properties of single-walled
      boron nitride nanotubes. Excitonic effects are shown to be even more important in
      BN nanotubes than in carbon nanotubes. Electron-hole interactions give rise to
      complexes of bright (and dark) excitons, which qualitatively alter the optical
      response. Excitons with a binding energy larger than 2 eV are found in the BN
      nanotubes. Moreover, unlike the carbon nanotubes, theory predicts that these
      exciton states are comprised of coherent supposition of transitions from several
      different subband pairs, giving rise to novel behaviors.

PMID- 16605934
TI  - Sublimation of atomic layers from a chromium surface.
AB  - We employ low-energy electron microscopy to study the kinetics of thermal
      etching, or sublimation, of Cr(001) at approximately 1100 K. Atomic layers are
      removed from the surface by spontaneous nucleation and growth of two-dimensional
      vacancy islands, by rotation of spiral steps, and by island decay. The growth
      rates of vacancy islands and the rotation frequencies of double spirals are
      measured as a function of temperature, and the results are correlated with
      activation barriers of surface processes. Mass transport between the surface and
      bulk is shown to be unimportant.

PMID- 16605935
TI  - Inverse Anderson transition caused by flatbands.
AB  - We propose a new disorder-induced insulator-metal transition of one-electron
      states, which may be called the "inverse Anderson transition." We first make a
      highly degenerated localized states by constructing a three-dimensional periodic
      system possessing only flat dispersion relations. When we introduce a disorder
      into it, a finite-size scaling of the level statistics shows two clear
      (localization-delocalization and delocalization-localization) transitions for a
      wide range of the energy, with increasing the degree of disorder. These
      transitions are confirmed also by finding the system-size-independent
      characteristic of the wave function.

PMID- 16605936
TI  - Bound states in a two-dimensional short range potential induced by the spin-orbit
      interaction.
AB  - We have discovered an unexpected and surprising fact: a 2D axially symmetric
      short-range potential contains an infinite number of the levels of negative
      energy if one takes into account the spin-orbit (SO) interaction. For a shallow
      well (meU0R2/h2<<1, where me is the effective mass and U0 and R are the depth and
      the radius of the well, respectively) and weak SO coupling (/alpha/meR/h<<1,
      where alpha is the SO coupling constant) exactly one twofold degenerate bound
      state exists for each value of the half-integer moment j=m+1/2, and the
      corresponding binding energy Em extremely rapidly decreases with increasing m.

PMID- 16605937
TI  - Electric-field effect on the angle-dependent magnetotransport properties of quasi
      one-dimensional conductors.
AB  - We report a novel electric field effect on angular dependent magnetotransport in
      quasi-one-dimensional layered conductors with a pair of sheetlike Fermi surfaces.
      Under tilted magnetic fields and additional interlayer electric fields,
      semiclassical electron orbits on two Fermi sheets become periodic at different
      magnetic field orientations. This causes double splitting of the Lebed's
      commensurability resonance in interlayer transport, and the amount of splitting
      allows us to estimate the Fermi velocity directly. We have successfully
      demonstrated this effect in the organic conductor alpha-(BEDT-TTF)2KHg(SCN)4.

PMID- 16605938
TI  - Magnetic field symmetry and phase rigidity of the nonlinear conductance in a
      ring.
AB  - We have performed nonlinear transport measurements as a function of a
      perpendicular magnetic field in a semiconductor Aharonov-Bohm ring connected to
      two leads. While the voltage-symmetric part of the conductance is symmetric in
      the magnetic field, the voltage-antisymmetric part of the conductance is not
      symmetric. These symmetry relations are compatible with the scattering theory for
      nonlinear mesoscopic transport. The observed asymmetry can be tuned continuously
      by changing the gate voltages near the arms of the ring, showing that the phase
      of the nonlinear conductance in a two-terminal interferometer is not rigid, in
      contrast with the case for the linear conductance.

PMID- 16605939
TI  - Surface criticality and multifractality at localization transitions.
AB  - We develop the concept of surface multifractality for localization-delocalization
      (LD) transitions in disordered electronic systems. We point out that the critical
      behavior of various observables related to wave functions near a boundary at a LD
      transition is different from that in the bulk. We illustrate this point with a
      calculation of boundary critical and multifractal behavior at the 2D spin quantum
      Hall transition and in a 2D metal at scales below the localization length.

PMID- 16605940
TI  - Drastic reduction of shot noise in semiconductor superlattices.
AB  - We have found experimentally that the shot noise of the tunneling current I
      through an undoped semiconductor superlattice is reduced with respect to the
      Poissonian noise value 2eI, and that the noise approaches 1/3 of that value in
      superlattices whose quantum wells are strongly coupled. On the other hand, when
      the coupling is weak or when a strong electric field is applied to the
      superlattice, the noise becomes Poissonian. Although our results are
      qualitatively consistent with existing theories for one-dimensional multibarrier
      structures, the theories cannot account for the dependence of the noise on
      superlattice parameters that we have observed.

PMID- 16605941
TI  - Interaction effects and pseudogap in two-dimensional lateral tunnel junctions.
AB  - Tunneling characteristics of a two-dimensional lateral tunnel junction are
      reported. A pseudogap on the order of Coulomb energy is detected in the tunneling
      density of states (TDOS) when two identical two-dimensional electron systems are
      laterally separated by a thin energy barrier. The Coulombic pseudogap remains
      robust well into the quantum Hall regime until it is overshadowed by the
      cyclotron gap in the TDOS. The pseudogap is modified by the in-plane magnetic
      field, demonstrating a nontrivial effect of the in-plane magnetic field on the
      electron-electron interaction.

PMID- 16605942
TI  - Half-integer filling-factor states in quantum dots.
AB  - The emergence of half-integer filling-factor states, such as upsilon=5/2 and 7/2,
      is found in quantum dots by using numerical many-electron methods. These states
      have interesting similarities and differences with their counterstates found in
      the two-dimensional electron gas. The upsilon=1/2 states in quantum dots are
      shown to have high overlaps with the composite fermion states. The lower overlap
      of the Pfaffian state indicates that electrons might not be paired in quantum dot
      geometry. The predicted upsilon=5/2 state has a high spin polarization, which may
      have an impact on the spin transport through quantum dot devices.

PMID- 16605943
TI  - Excitation spectrum of two correlated electrons in a lateral quantum dot with
      negligible Zeeman splitting.
AB  - The excitation spectrum of a two-electron quantum dot is investigated by
      tunneling spectroscopy in conjunction with theoretical calculations. The dot made
      from a material with negligible Zeeman splitting has a moderate spatial
      anisotropy leading to a splitting of the two lowest triplet states at zero
      magnetic field. In addition to the well-known triplet excitation at zero magnetic
      field, two additional excited states are found at finite magnetic field. The
      lower one is identified as the second excited singlet state on the basis of an
      avoided crossing with the first excited singlet state at finite fields. The
      measured spectra are in remarkable agreement with exact-diagonalization
      calculations. The results prove the significance of electron correlations and
      suggest the formation of a state with Wigner-molecular properties at low magnetic
      fields.

PMID- 16605944
TI  - Detection of the electron spin resonance of two-dimensional electrons at large
      wave vectors.
AB  - We have investigated the electron spin resonance at nonzero wave vector in GaAs
      single quantum wells by combining the virtues of high frequency surface acoustic
      wave generation to produce excitations with large wave numbers with a sensitive
      optical scheme to detect resonant absorption. The observed large deviations from
      the single particle Zeeman energy are attributed to the exchange interaction. The
      enhancement of the electronic g* factor is, however, substantially smaller
      compared with theoretical predictions for spin waves when adopting a bare Coulomb
      interaction potential.

PMID- 16605945
TI  - Experimental demonstration of an oscillator stabilized Josephson flux qubit.
AB  - We experimentally demonstrate the use of a superconducting transmission line,
      shorted at both ends, to stabilize the operation of a tunable flux qubit. Using
      harmonic-oscillator stabilization and pulsed dc operation, we have observed
      Larmor oscillations with a single shot visibility of 90%. In another qubit, the
      visibility was 60% and there was no measurable visibility reduction after 35 ns.

PMID- 16605946
TI  - Spin proximity effect in ultrathin superconducting Be-Au bilayers.
AB  - We present a detailed study of the effects of interface spin-orbit coupling on
      the critical field behavior of ultrathin superconducting Be/Au bilayers. Parallel
      field measurements were made in bilayers with Be thicknesses in the range of d=2
      30 nm and Au coverages of 0.5 nm. Though the Au had little effect on the
      superconducting gap, it produced profound changes in the spin states of the
      system. In particular, the parallel critical field exceeded the Clogston limit by
      an order of magnitude in the thinnest films studied. In addition, the parallel
      critical field unexpectedly scaled as [FORMULA: SEE TEXT], suggesting that the
      spin-orbit coupling energy was proportional to Delta0/d2. Tilted field
      measurements showed that, contrary to recent theory, the interface spin-orbit
      coupling induces a large in-plane superconducting susceptibility but only a very
      small transverse susceptibility.

PMID- 16605947
TI  - High-contrast dispersive readout of a superconducting flux qubit using a
      nonlinear resonator.
AB  - We demonstrate high-contrast state detection of a superconducting flux qubit.
      Detection is realized by probing the microwave transmission of a nonlinear
      resonator, based on a SQUID. Depending on the driving strength of the resonator,
      the detector can be operated in the monostable or the bistable mode. The bistable
      operation combines high-sensitivity with intrinsic latching. The measured
      contrast of Rabi oscillations is as high as 87%; of the missing 13%, only 3% of
      the loss of contrast is unaccounted for. Experiments involving two consecutive
      detection pulses are consistent with preparation of the qubit state by the first
      measurement.

PMID- 16605948
TI  - Nonuniform self-organized dynamical states in superconductors with periodic
      pinning.
AB  - We consider magnetic flux moving in superconductors with periodic pinning arrays.
      We show that sample heating by moving vortices produces negative differential
      resistivity (NDR) of both N and S type (i.e., N- and S-shaped) in the voltage
      current characteristic (VI curve). The uniform flux flow state is unstable in the
      NDR region of the VI curve. Domain structures appear during the NDR part of the
      VI curve of an N type, while a filamentary instability is observed for the NDR of
      an S type. The simultaneous existence of the NDR of both types gives rise to the
      appearance of striking self-organized (both stationary and nonstationary) two
      dimensional dynamical structures.

PMID- 16605949
TI  - Impurity-induced local magnetism and density of states in the superconducting
      state of YBa2Cu3O7.
AB  - 17O NMR is used to probe the local influence of nonmagnetic Zn and magnetic Ni
      impurities in the superconducting state of optimally doped high TC YBa2Cu3O7. Zn
      and Ni induce a staggered paramagnetic polarization, similar to that evidenced
      above TC, with a typical extension xi=3 cell units for Zn and xi>or=3 for Ni. In
      addition, Zn is observed to induce a local density of states near the Fermi
      energy in its neighborhood, which also decays over about 3 cell units. Its
      magnitude decreases sharply with increasing temperature. This allows direct
      comparison with the STM observations done in BiSCCO.

PMID- 16605950
TI  - Vacuum Rabi oscillations in a macroscopic superconducting qubit oscillator
      system.
AB  - We have observed the coherent exchange of a single energy quantum between a flux
      qubit and a superconducting LC circuit acting as a quantum harmonic oscillator.
      The exchange of an energy quantum is known as the vacuum Rabi oscillation: the
      qubit is oscillating between the excited state and the ground state and the
      oscillator between the vacuum state and the first excited state. We also show
      that we can detect the state of the oscillator with the qubit and thereby
      obtained evidence of level quantization of the LC circuit. Our results support
      the idea of using oscillators as couplers of solid-state qubits.

PMID- 16605951
TI  - Epitaxial stabilization of ferromagnetism in the nanophase of FeGe.
AB  - Epitaxial nanocrystals of FeGe have been stabilized on Ge(111). The nanocrystals
      assume a quasi-one-dimensional shape as they grow exclusively along the <110>
      direction of the Ge(111) substrate, culminating in a compressed monoclinic
      modification of FeGe. Whereas monoclinic FeGe is antiferromagnetic in the bulk,
      the nanowires are surprisingly strong ferromagnets below approximately 200 K with
      an average magnetic moment of 0.8 microB per Fe atom. Density functional
      calculations indicate an unusual stabilization mechanism for the observed
      ferromagnetism: lattice compression destabilizes the antiferromagnetic Peierls
      like ground state observed in the bulk while increased p-d hybridization
      suppresses the magnetic moments and stabilizes ferromagnetism.

PMID- 16605952
TI  - Spin dynamics and magnetic order in magnetically frustrated Tb2Sn2O7.
AB  - We report a study of the geometrically frustrated magnetic material Tb2Sn2O7 by
      the positive muon-spin relaxation technique. No signature of a static
      magnetically ordered state is detected while neutron magnetic reflections are
      observed in agreement with a published report. This is explained by the dynamical
      nature of the ground state of Tb2Sn2O7: the Tb3+ magnetic moment characteristic
      fluctuation time is approximately 10(-10) s. The strong effect of the magnetic
      field on the muon-spin-lattice relaxation rate at low fields indicates a large
      field-induced increase of the magnetic density of states of the collective
      excitations at low energy.

PMID- 16605953
TI  - Efficient magnetization reversal with noisy currents.
AB  - We propose to accelerate reversal of the ferromagnetic order parameter in spin
      valves by electronic noise. By solving the stochastic equations of motion we show
      that the current-induced magnetization switching time is drastically reduced by a
      modest level of externally generated current (voltage) noise. This also leads to
      a significantly lower power consumption for the switching process.

PMID- 16605954
TI  - Controlling the spin polarization of nanostructures on magnetic substrates.
AB  - It is shown that, by utilizing spin-selective quantum interference, the spin
      polarization of nanostructures deposited on a magnetic substrate with a surface
      state can be strongly modulated locally and energetically by an appropriate
      structural design. This finding is deduced from state-of-the-art ab initio
      calculations and interpreted within an analytical model. We present results for
      hexagonal Cu corrals and mesoscopic triangular Co islands on Co-covered Cu(111).
      These systems are experimentally feasible, and the effect should be detectable
      with current technology.

PMID- 16605955
TI  - Nanometer linear focusing of hard x rays by a multilayer Laue lens.
AB  - We report on a type of linear zone plate for nanometer-scale focusing of hard x
      rays, a multilayer Laue lens (MLL), produced by sectioning a multilayer and
      illuminating it in Laue diffraction geometry. Because of its large optical depth,
      a MLL spans the diffraction regimes applicable to a thin Fresnel zone plate and a
      crystal. Coupled wave theory calculations indicate that focusing to 5 nm or
      smaller with high efficiency should be possible. Partial MLL structures with
      outermost zone widths as small as 10 nm have been fabricated and tested with 19.5
      keV synchrotron radiation. Focal sizes as small as 30 nm with efficiencies up to
      44% are measured.

PMID- 16605956
TI  - Experimental evidence of zero forward scattering by magnetic spheres.
AB  - Magnetically induced diffraction patterns by micron sized magnetic spheres
      dispersed in a ferrofluid disappear at a certain critical magnetic field. This
      critical field is found to depend on the concentration of the ferrofluid and on
      the volume of the magnetic spheres. We attribute this effect to the zero forward
      scattering by magnetic spheres as predicted by Kerker, Wang, and Giles [J. Opt.
      Soc. Am. 73, 765 (1983)]. We suggest that such a dispersion can be used to study
      the optical analogues of localization of electrons in condensed matter, the Hall
      effect, and the anisotropic diffusion, etc. The combination of the micron sized
      magnetic spheres and the ferrofluid will also be useful to design magnetically
      tunable photonic devices.

PMID- 16605957
TI  - Temperature dependence of the optical transition energies of carbon nanotubes:
      the role of electron-phonon coupling and thermal expansion.
AB  - Tunable Raman spectroscopy is used to measure the optical transition energies Eii
      of individual single wall carbon nanotubes. Eii is observed to shift down in
      energy by as much as 50 meV, from -160 to 300 degrees C, in contrast with
      previous measurements performed on nanotubes in alternate environments, which
      show upshifts and downshifts in Eii with temperature. We determine that electron
      phonon coupling explains our experimental observations of nanotubes suspended in
      air, neglecting thermal expansion. In contrast, for nanotubes in surfactant or in
      bundles, thermal expansion of the nanotubes' environment exerts a nonisotropic
      pressure on the nanotube that dominates over the effect of electron-phonon
      coupling.

PMID- 16605958
TI  - Self-tuned quantum dot gain in photonic crystal lasers.
AB  - We demonstrate that very few (2-4) quantum dots as a gain medium are sufficient
      to realize a photonic-crystal laser based on a high-quality nanocavity. Photon
      correlation measurements show a transition from a thermal to a coherent light
      state proving that lasing action occurs at ultralow thresholds. Observation of
      lasing is unexpected since the cavity mode is in general not resonant with the
      discrete quantum dot states and emission at those frequencies is suppressed. In
      this situation, the quasicontinuous quantum dot states become crucial since they
      provide an energy-transfer channel into the lasing mode, effectively leading to a
      self-tuned resonance for the gain medium.

PMID- 16605959
TI  - Stabilization of monodomain polarization in ultrathin PbTiO3 films.
AB  - Using in situ high-resolution synchrotron x-ray scattering, the Curie temperature
      TC has been determined for ultrathin c-axis epitaxial PbTiO3 films on conducting
      substrates (SrRuO3 on SrTiO3), with surfaces exposed to a controlled vapor
      environment. The suppression of TC was relatively small, even for the thinnest
      film (1.2 nm). We observe that 180 degrees stripe domains do not form, indicating
      that the depolarizing field is compensated by free charge at both interfaces.
      This is confirmed by ab initio calculations that find polar ground states in the
      presence of ionic adsorbates.

PMID- 16605960
TI  - Polar domains in lead titanate films under tensile strain.
AB  - Thin films of PbTiO3, a classical ferroelectric, have been grown under tensile
      strain on single-crystal substrates of DyScO3. The films, of only 5 nm thickness,
      grow fully coherent with the substrate, as evidenced by synchrotron x-ray
      diffraction. A mapping of the reciprocal space reveals intensity modulations
      (satellites) due to regularly spaced polar domains in which the polarization
      appears rotated away from the substrate normal, characterizing a low-symmetry
      phase not observed in the bulk material. This could have important practical
      implications since these phases are known to be responsible for ultrahigh
      piezoelectric responses in complex systems.

PMID- 16605961
TI  - Scale dependence of branching in arterial and bronchial trees.
AB  - Although models of branching in arterial and bronchial trees often predict a
      dependence of bifurcation parameters on the scale of the bifurcating vessels,
      direct verification of this dependence by comparison with data is uncommon. We
      compare measurements of bifurcation parameters of airways and arterial trees of
      different mammals as a function of scale to general features predicted by
      theoretical models based on minimization of pumping power and network volume. We
      find that the size dependence is more complex than existing theories based solely
      on energy and volume minimization explain, and suggest additional factors that
      may govern the branching at different scales.

PMID- 16605962
TI  - Inference of DNA sequences from mechanical unzipping: an ideal-case study.
AB  - The performances of Bayesian inference to predict the sequence of DNA molecules
      from fixed-force unzipping experiments are investigated. We show that the
      probability of misprediction decreases exponentially with the amount of collected
      data. The decay rate is calculated as a function of biochemical parameters
      (binding free energies), the sequence content, the applied force, the elastic
      properties of a DNA single strand, and time resolution.

PMID- 16605963
TI  - Ion complexation: a route to enhanced block copolymer alignment with electric
      fields.
AB  - We investigate the enhanced alignment of lamellar microdomains under an electric
      field by addition of lithium chloride (LiCl) into polystyrene-block-poly(methyl
      methacrylate) (PS-b-PMMA) copolymers. A significant increase of dielectric
      contrast resulting from the formation of lithium-PMMA complexes markedly reduces
      the critical electric field strength required to overcome the preferential
      interactions of one block with the substrate, providing a route to achieve the
      complete alignment of microdomains in block copolymer thin films.

PMID- 16605964
TI  - Multiscale coarse graining of diblock copolymer self-assembly: from monomers to
      ordered micelles.
AB  - Starting from a microscopic lattice model, we investigate clustering,
      micellization, and micelle ordering in semidilute solutions of AB diblock
      copolymers in a selective solvent. To bridge the gap in length scales, from
      monomers to ordered micellar structures, we implement a two-step coarse-graining
      strategy, whereby the AB copolymers are mapped onto ultrasoft dumbells with
      monomer-averaged effective interactions between the centers of mass of the
      blocks. Monte Carlo simulations of this coarse-grained model yield clear-cut
      evidence for self-assembly into micelles with a mean aggregation number n
      approximately 100 beyond a critical concentration. At a slightly higher
      concentration the micelles spontaneously undergo a disorder-order transition to a
      cubic phase. We determine the effective potential between these micelles from
      first principles.

PMID- 16605965
TI  - Clustering of polarity reversals of the geomagnetic field.
AB  - Often in nature the temporal distribution of inhomogeneous stochastic point
      processes can be modeled as a realization of renewal Poisson processes with a
      variable rate. Here we investigate one of the classical examples, namely, the
      temporal distribution of polarity reversals of the geomagnetic field. In spite of
      the commonly used underlying hypothesis, we show that this process strongly
      departs from a Poisson statistics, the origin of this failure stemming from the
      presence of temporal clustering. We find that a Levy statistics is able to
      reproduce paleomagnetic data, thus suggesting the presence of long-range
      correlations in the underlying dynamo process.

PMID- 16605966
TI  - BEC-BCS crossover in "magnetized" Feshbach-resonantly paired superfluids.
AB  - We map out the detuning-magnetization phase diagram for a magnetized (unequal
      number of atoms in two pairing hyperfine states) gas of fermionic atoms
      interacting via an s-wave Feshbach resonance (FR). The phase diagram is dominated
      by the coexistence of a magnetized normal gas and a singlet-paired superfluid
      with the latter exhibiting a BCS-Bose Einstein condensate crossover with reduced
      FR detuning. On the BCS side of strongly overlapping Cooper pairs, a sliver of
      finite-momentum paired Fulde-Ferrell-Larkin-Ovchinnikov magnetized phase
      intervenes between the phase-separated and normal states. In contrast, for large
      negative detuning a uniform, polarized superfluid, that is, a coherent mixture of
      singlet Bose-Einstein-condensed molecules and fully magnetized single-species
      Fermi sea, is a stable ground state.

PMID- 16605967
TI  - Qubit assisted probing of coherence between mesoscopic states of an apparatus.
AB  - I present a general scheme through which the evidence of a superposition
      involving distinct states of a mesoscopic system can be probed. The scheme relies
      on a single qubit being coupled to a mesoscopic harmonic oscillator in such a way
      that it can be used to both prepare and probe a superposition of states of the
      oscillator. Two potentially realizable implementations, one with a single flux
      qubit coupled to an LC circuit, and the other with a single ion-trap qubit
      coupled to the collective motion of several ions, are proposed.

PMID- 16605968
TI  - Driving defect modes of Bose-Einstein condensates in optical lattices.
AB  - We present an approximate analytical theory and direct numerical computation of
      defect modes of a Bose-Einstein condensate loaded in an optical lattice and
      subject to an additional localized (defect) potential. Some of the modes are
      found to be remarkably stable and can be driven along the lattice by means of a
      defect moving following a steplike function defined by the period of Josephson
      oscillations and the macroscopic stability of the atoms.

PMID- 16605969
TI  - Critical temperature of a trapped Bose gas: comparison of theory and experiment.
AB  - We apply the projected Gross-Pitaevskii equation (PGPE) formalism to the
      experimental problem of the shift in critical temperature Tc of a harmonically
      confined Bose gas as reported in Gerbier et al., Phys. Rev. Lett. 92, 030405
      (2004). The PGPE method includes critical fluctuations and we find the results
      differ from various mean-field theories, and are in best agreement with
      experimental data. To unequivocally observe beyond mean-field effects, however,
      the experimental precision must either improve by an order of magnitude, or
      consider more strongly interacting systems. This is the first application of a
      classical field method to make quantitative comparison with experiment.

PMID- 16605970
TI  - Bose-Einstein condensates in rotating lattices.
AB  - Strongly interacting bosons in a two-dimensional rotating square lattice are
      investigated via a modified Bose-Hubbard Hamiltonian. Such a system corresponds
      to a rotating lattice potential imprinted on a trapped Bose-Einstein condensate.
      Second-order quantum phase transitions between states of different symmetries are
      observed at discrete rotation rates. For the square lattice we study, there are
      four possible ground-state symmetries.

PMID- 16605971
TI  - Generic Bell inequalities for multipartite arbitrary dimensional systems.
AB  - We present generic Bell inequalities for multipartite arbitrary dimensional
      systems. The inequalities that any local realistic theory must obey are violated
      by quantum mechanics for even dimensional systems. A large set of variants are
      shown to naturally emerge from the generic Bell inequalities. We discuss
      particular variants of Bell inequalities that are violated for all the systems
      including odd dimensional systems.

PMID- 16605972
TI  - Macroscopic thermal entanglement due to radiation pressure.
AB  - Can entanglement and the quantum behavior in physical systems survive at
      arbitrary high temperatures? In this Letter we show that this is the case for a
      electromagnetic field mode in an optical cavity with a movable mirror in a
      thermal state. We also identify two different dynamical regimes of generation of
      entanglement separated by a critical coupling strength.

PMID- 16605973
TI  - Measuring nonlinear functionals of quantum harmonic oscillator states.
AB  - Using only linear interactions and a local parity measurement we show how
      entanglement can be detected between two harmonic oscillators. The scheme
      generalizes to measure both linear and nonlinear functionals of an arbitrary
      oscillator state. This leads to many applications including purity tests,
      eigenvalue estimation, entropy, and distance measures--all without the need for
      nonlinear interactions or complete state reconstruction. Remarkably, experimental
      realization of the proposed scheme is already within the reach of current
      technology with linear optics.

PMID- 16605974
TI  - Teleportation and dense coding with genuine multipartite entanglement.
AB  - We present an explicit protocol E0 for faithfully teleporting an arbitrary two
      qubit state via a genuine four-qubit entangled state. By construction, our four
      partite state is not reducible to a pair of Bell states. Its properties are
      compared and contrasted with those of the four-party Greenberger-Horne-Zeilinger
      and W states. We also give a dense coding scheme D0 involving our state as a
      shared resource of entanglement. Both D0 and E0 indicate that our four-qubit
      state is a likely candidate for the genuine four-partite analogue to a Bell
      state.

PMID- 16605975
TI  - Time-optimal quantum evolution.
AB  - We present a general framework for finding the time-optimal evolution and the
      optimal Hamiltonian for a quantum system with a given set of initial and final
      states. Our formulation is based on the variational principle and is analogous to
      that for the brachistochrone in classical mechanics. We reduce the problem to a
      formal equation for the Hamiltonian which depends on certain constraint functions
      specifying the range of available Hamiltonians. For some simple examples of the
      constraints, we explicitly find the optimal solutions.

PMID- 16605976
TI  - Demonstration of quantum telecloning of optical coherent states.
AB  - We demonstrate unconditional telecloning for the first time. In particular, we
      symmetrically and unconditionally teleclone coherent states of light from one
      sender to two receivers, achieving a fidelity for each clone of F = 0.58 +/-
      0.01, which surpasses the classical limit. This is a manipulation of a new type
      of multipartite entanglement whose nature is neither purely bipartite nor purely
      tripartite.

PMID- 16605977
TI  - Fractionalization, topological order, and quasiparticle statistics.
AB  - We argue, based on general principles, that topological order is essential to
      realize fractionalization in gapped insulating phases in dimensions d > or = 2.
      In d = 2 with genus g, we derive the existence of the minimum topological
      degeneracy q(g) if the charge is fractionalized in units of 1/q, irrespective of
      microscopic model or effective theory. Furthermore, if the quasiparticle is
      either boson or fermion, it must be at least q(2g).

PMID- 16605978
TI  - Cold atom clock test of Lorentz invariance in the matter sector.
AB  - We report on a new experiment that tests for a violation of Lorentz invariance
      (LI), by searching for a dependence of atomic transition frequencies on the
      orientation of the spin of the involved states (Hughes-Drever type experiment).
      The atomic frequencies are measured using a laser cooled 133Cs atomic fountain
      clock, operating on a particular combination of Zeeman substates. We analyze the
      results within the framework of the Lorentz violating standard model extension
      (SME), where our experiment is sensitive to a largely unexplored region of the
      SME parameter space, corresponding to first measurements of four proton
      parameters and improvements by 11 and 13 orders of magnitude on the determination
      of four others. In spite of the attained uncertainties, and of having extended
      the search into a new region of the SME, we still find no indication of LI
      violation.

PMID- 16605979
TI  - Cosmology with massive neutrinos coupled to dark energy.
AB  - Cosmological consequences of a coupling between massive neutrinos and dark energy
      are investigated. In such models, the neutrino mass is a function of a scalar
      field, which plays the role of dark energy. The evolution of the background and
      cosmological perturbations are discussed. We find that mass-varying neutrinos can
      leave a significant imprint on the anisotropies in the cosmic microwave
      background and even lead to a reduction of power on large angular scales.

PMID- 16605980
TI  - Almost certain escape from black holes in final state projection models.
AB  - Recent models of the black-hole final state suggest that quantum information can
      escape from a black hole by a process akin to teleportation. These models rely on
      a controversial process called final-state projection. This Letter discusses the
      self-consistency of the final-state projection hypothesis and investigates escape
      from black holes for arbitrary final states and for generic interactions between
      matter and Hawking radiation. Quantum information escapes with fidelity
      approximately = (8/3pi)2: only half a bit of quantum information is lost on
      average, independent of the number of bits that escape from the hole.

PMID- 16605981
TI  - Testing for w < -1 in the solar system.
AB  - In scalar-tensor theories of gravity, the equation of state of dark energy, w,
      can become smaller than -1 without violating any energy condition. The value of w
      today is tied to the level of deviations from general relativity which, in turn,
      is constrained by solar system and pulsars timing experiments. The conditions on
      these local constraints for w to be significantly less than -1 are established.
      It is demonstrated that this requires us to consider theories that differ from
      the Jordan-Fierz-Brans-Dicke theory and that involve either a steep coupling
      function or a steep potential. It is also shown how a robust measurement of w
      could probe scalar-tensor theories.

PMID- 16605982
TI  - Observable N-N oscillation in high scale seesaw models.
AB  - We discuss a realistic high scale (nu(B-L) approximately 10(12) GeV)
      supersymmetric seesaw model based on the gauge group SU(2)L x SU(2)R x SU(4)c
      where neutron-antineutron oscillation can be in the observable range. This is
      contrary to the naive dimensional arguments which say that tau(N-N) is
      proportional to nu(B-L)5 and should therefore be unobservable for seesaw scale
      nu(B-L) > or = 10(5) GeV. Two reasons for this enhancement are (i) accidental
      symmetries which keep some of the diquark Higgs masses at the weak scale and (ii)
      a new supersymmetric contribution from a lower dimensional operator. The net
      result is that tau(N-N) is proportional to nu(B-L)2 nu(wk)3 rather than nu(B-L)5.
      The model also can explain the origin of matter via the leptogenesis mechanism
      and predicts light diquark states which can be produced at LHC.

PMID- 16605983
TI  - Duality in left-right symmetric seesaw mechanism.
AB  - We consider type I + II seesaw mechanism, where the exchanges of both right
      handed neutrinos and isotriplet Higgs bosons contribute to the neutrino mass.
      Working in the left-right symmetric framework and assuming the mass matrix of
      light neutrinos m(v) and the Dirac-type Yukawa couplings to be known, we find the
      triplet Yukawa coupling matrix f, which carries the information about the masses
      and mixing of the right-handed neutrinos. We show that in this case there exists
      a duality: for any solution f, there is a dual solution [symbol: see text] =
      m(v)/nu(L) - f, where nu(L) is the vacuum expectation value of the triplet Higgs
      boson. Thus, unlike in pure type I (II) seesaw, there is no unique allowed
      structure for the matrix f. For n lepton generations the number of solutions is
      2(n). We develop an exact analytic method of solving the seesaw nonlinear matrix
      equation for f.

PMID- 16605985
TI  - Exclusive measurement of the nonmesonic weak decay of the lambda(5)He
      hypernucleus.
AB  - We performed a coincidence measurement of two nucleons emitted from the
      nonmesonic weak decay of lambda(5)He formed via the 6Li(pi+, K+) reaction. The
      energies of the two nucleons and the pair number distributions in the opening
      angle between them were measured. In both np and nn pairs, we observed a clean
      back-to-back correlation coming from the two-body weak reactions of lambda p -->
      np and lambda n --> nn, respectively. The ratio of the nucleon pair numbers was
      N(nn)/N(np) = 0.45 +/- 0.11(stat) +/- 0.03(syst) in the kinematic region of cos
      theta(NN) < -0.8. Since each decay mode was exclusively detected, the measured
      ratio should be close to the ratio of gamma(lambda p --> np)/gamma(lambda n -->
      nn). The ratio is consistent with recent theoretical calculations based on the
      heavy meson and/or direct-quark exchange picture.

PMID- 16605986
TI  - Collective non-Abelian instabilities in a melting color glass condensate.
AB  - We present first results for (3 + 1)D simulations of SU(2) Yang-Mills equations
      for matter expanding into the vacuum after a heavy ion collision. Violations of
      boost invariance cause a non-Abelian Weibel instability leading soft modes to
      grow with proper time tau as exp(gamma square root(g2 mu tau)), where g2 mu is a
      scale arising from the saturation of gluons in the nuclear wave function. The
      scale for the growth rate gamma is set by a plasmon mass, defined as omega(pl) =
      kappa0 square root(g2 mu/tau)), generated dynamically in the collision. We
      compare the numerical ratio gamma/kappa0 to the corresponding value predicted by
      the hard thermal loop formalism for anisotropic plasmas.

PMID- 16605987
TI  - Strangeness condensation by expanding about the fixed point of the Harada
      Yamawaki vector manifestation.
AB  - Building on, and extending, the result of a higher-order in-medium chiral
      perturbation theory combined with renormalization group arguments and a variety
      of observations of the vector manifestation of Harada-Yamawaki hidden local
      symmetry theory, we obtain a surprisingly simple description of kaon condensation
      by fluctuating around the "vector manifestation" fixed point identified to be the
      chiral restoration point. Our development establishes that strangeness
      condensation takes place at approximately 3n0 where n0 is nuclear matter density.
      This result depends only on the renormalization-group (RG) behavior of the vector
      interactions, other effects involved in fluctuating about the bare vacuum in so
      many previous calculations being irrelevant in the RG about the fixed point. Our
      results have major effects on the collapse of neutron stars into black holes.

PMID- 16605988
TI  - Fast ground state manipulation of neutral atoms in microscopic optical traps.
AB  - We demonstrate Rabi flopping at MHz rates between ground hyperfine states of
      neutral 87Rb atoms that are trapped in two micron sized optical traps. Using
      tightly focused laser beams we demonstrate high fidelity, site specific Rabi
      rotations with cross talk on neighboring sites separated by 8 microm at the level
      of 10(-3). Ramsey spectroscopy is used to measure a dephasing time of 870 micros,
      which is approximately 5000 longer than the time for a pi/2 pulse.

PMID- 16605989
TI  - Chirped attosecond photoelectron spectroscopy.
AB  - We study analytically the photoionization of a coherent superposition of
      electronic states and show that chirped pulses can measure attosecond time scale
      electron dynamics just as effectively as transform-limited attosecond pulses of
      the same bandwidth. The chirped pulse with a frequency-dependent phase creates
      the interfering photoelectron amplitudes that measure the electron dynamics. We
      show that at a given pump-probe time delay the differential asymmetry oscillates
      as a function of photoelectron energy. Our results suggest that the important
      parameter for attosecond science is not the pulse duration, but the bandwidth of
      phased radiation.

PMID- 16605990
TI  - Fluorescence emission of excited hydrogen atoms after core excitation of water
      vapor.
AB  - The Balmer emission from atomic hydrogen has been recorded across the resonances
      at the oxygen K edge of the water molecule using synchrotron radiation
      excitation. The emission is observed to be strongest at excitations to Rydberg
      resonances. The observations are interpreted using a qualitative model for the
      dynamics of the core-to-Rydberg excited molecule. The model links the quantum
      state of the core-excited water molecule via resonant Auger decay and subsequent
      dissociation to the state of the fluorescing hydrogen atom.

PMID- 16605984
TI  - Eta' photoproduction on the proton for photon energies from 1.527 to 2.227 GeV.
AB  - Differential cross sections for the reaction gamma p --> eta' p have been
      measured with the CLAS spectrometer and a tagged photon beam with energies from
      1.527 to 2.227 GeV. The results reported here possess much greater accuracy than
      previous measurements. Analyses of these data suggest for the first time the
      coupling of the eta'N channel to both the S11(1535) and P11(1710) resonances,
      known to couple strongly to the etaN channel in photoproduction on the proton,
      and the importance of J = 3/2 resonances in the process.

PMID- 16605991
TI  - Measurement of the decay rate of the negative ion of positronium (Ps-).
AB  - A new determination of the decay rate of the negative ion of positronium (Ps-),
      using a beam-foil method and a stripping-based detection technique, is reported.
      The measured result of gamma = 2.089(15) ns(-1) is a factor of 6 more precise
      than the previous experimental value of gamma = 2.09(9) ns(-1), and is in
      excellent agreement with the theoretical value of gamma = 2.086(6) ns(-1).

PMID- 16605992
TI  - Harmonic entanglement with second-order nonlinearity.
AB  - We investigate the second-order nonlinear interaction as a means to generate
      entanglement between fields of differing wavelengths and show that perfect
      entanglement can, in principle, be produced between the fundamental and second
      harmonic fields in these processes. Neither pure second-harmonic generation nor
      parametric oscillation optimally produce entanglement; such optimal entanglement
      is rather produced by an intermediate process.

PMID- 16605993
TI  - Can two-photon correlation of chaotic light be considered as correlation of
      intensity fluctuations?
AB  - Two-photon correlation phenomena, including the historical experiment of Hanbury
      Brown and Twiss, may have to be described quantum mechanically, regardless of
      whether the source of radiation is classical or quantum. Supporting this point,
      we present a ghost imaging type of second-order spatial correlation experiment of
      chaotic light to show that the classical understanding based on the concept of
      statistical intensity fluctuations does not give a correct interpretation for the
      observation. From a practical point of view, this experiment demonstrates the
      possibility of having high contrast lensless two-photon imaging with chaotic
      light, suggesting imaging applications for radiations for which no effective lens
      is available.

PMID- 16605994
TI  - Strong-field atomic phase matching.
AB  - We interpret a learning-control experiment with the goal of optimizing
      multiphoton population transfer in atomic sodium in the strong-field limit.
      Despite multiple experimental constraints, a learning algorithm discovers optimal
      pulses that can be understood in terms of a simple dynamic picture of the atom
      field interaction. We show that the shaped pulses counteract the dynamic Stark
      induced stimulated emission that would otherwise impede the efficient use of a pi
      pulse to invert a multiphoton transition.

PMID- 16605995
TI  - Observation of discrete surface solitons.
AB  - We report the first observation of discrete optical surface solitons at the
      interface between a nonlinear self-focusing waveguide lattice and a continuous
      medium. The effect of power on the localization process of these optical self
      trapped states at the edge of an AlGaAs waveguide array is investigated in
      detail. Our experimental results are in good agreement with theoretical
      predictions.

PMID- 16605996
TI  - Nonlinear magneto-optical Bragg gratings.
AB  - In magneto-optical gratings the magnetic dipolar coupling superimposed on the
      electric dipolar one introduces nonreciprocity and spectral discrimination
      between circular polarization states, measured by a Zeeman-like splitting of the
      photonic Bragg resonances. In a nonlinear regime the degree of nonreciprocity is
      modified by the photoinduced interplay of these splittings and their Stark-like
      shifts. We predict novel magneto-optical modulation schemes for switching between
      orthogonal circular polarization states of transmission or reflection operated by
      means of an intense linearly polarized optical pulse train.

PMID- 16605997
TI  - Conductivity and permittivity of two-dimensional metallic photonic crystals.
AB  - Two-dimensional metallic photonic crystals with different filling factors were
      manufactured and investigated by broadband terahertz spectroscopy. This technique
      allowed an independent determination of conductivity and dielectric permittivity
      in an extremely large dynamic range. Nearly ideal plasmonic behavior is observed
      for all compositions. Transmittance maxima are observed close to the plasma
      frequency and attributed to the longitudinal resonance. The plasmon frequencies
      agree well with existing calculations, while damping effects are underestimated
      by almost 1 order of magnitude.

PMID- 16605998
TI  - Observation of the critical regime near Anderson localization of light.
AB  - The transition from diffusive transport to localization of waves should occur for
      any type of classical or quantum wave in any media as long as the wavelength
      becomes comparable to the transport mean free path l*. The signatures of
      localization and those of absorption, or bound states, can, however, be similar,
      such that an unequivocal proof of the existence of wave localization in
      disordered bulk materials is still lacking. Here we present time resolved
      measurements of light transport through strongly scattering samples with kl*
      values as low as 2.5. In transmission, we observe deviations from diffusion which
      cannot be explained by absorption, sample geometry, or reduction in transport
      velocity. Furthermore, the deviations from classical diffusion increase strongly
      with decreasing l* as expected for a phase transition. This constitutes an
      experimental realization of the critical regime in the approach to Anderson
      localization.

PMID- 16605999
TI  - Delaying transition to turbulence by a passive mechanism.
AB  - Reducing skin friction is important in nature and in many technological
      applications. This reduction may be achieved by reducing stresses in turbulent
      boundary layers, for instance tailoring biomimetic rough skins. Here we take a
      second approach consisting of keeping the boundary layer laminar as long as
      possible by forcing small optimal perturbations. Because of the highly non-normal
      nature of the underlying linearized operator, these perturbations are highly
      amplified and able to modify the mean velocity profiles at leading order. We
      report results of wind-tunnel experiments in which we implement this concept by
      using suitably designed roughness elements placed on the skin to enforce nearly
      optimal perturbations. We show that by using this passive control technique it is
      possible to sensibly delay transition to turbulence.

PMID- 16606000
TI  - Coherent THz synchrotron radiation from a storage ring with high-frequency RF
      system.
AB  - The generation of brilliant, stable, and broadband coherent synchrotron radiation
      (CSR) in electron storage rings depends strongly on ring rf system properties
      such as frequency and gap voltage. We have observed intense coherent radiation at
      frequencies approaching the THz regime produced by the MIT-Bates South Hall Ring,
      which employs a high-frequency S-band rf system. The measured CSR spectral
      intensity enhancement with 2 mA stored current was up to 10,000 times above
      background for wave numbers near 3 cm(-1). The measurements also uncovered strong
      beam instabilities that must be suppressed if such a very high rf frequency
      electron storage ring is to become a viable coherent THz source.

PMID- 16606001
TI  - Intermediate nonlinear evolution of the Parker instability: formation of
      convection-induced discontinuities and absence of finite-time singularities.
AB  - Direct numerical simulations of the line-tied Parker (or magnetic Rayleigh
      Taylor) instability, based on the fully compressible ideal magnetohydrodynamic
      equations, are presented. In the intermediate nonlinear phase, the instability
      continues to grow exponentially in time and the plasma tends to develop
      convection-induced discontinuities in the form of shocklike coherent structures.
      No evidence of finite-time singularities is seen.

PMID- 16606002
TI  - Electric field in a double layer and the imparted momentum.
AB  - It is shown that the net momentum delivered by the large electric field inside a
      one-dimensional double layer is zero. This is demonstrated through an analysis of
      the momentum balance in the double layer at the boundary between the ionosphere
      and the aurora cavity. For the recently observed double layer in a current-free
      plasma expanding along a divergent magnetic field, an analysis of the evolution
      of the radially averaged variables shows that the increase of plasma thrust
      results from the magnetic-field pressure balancing the plasma pressure in the
      direction of acceleration, rather than from electrostatic pressure.

PMID- 16606003
TI  - Liquid-state properties of a one-component plasma.
AB  - As a consequence of strong collective behavior, the microscopic dynamics of the
      one-component plasma (OCP) differs significantly from that of ordinary liquids.
      We show that, when particle caging dominates, the OCP transport coefficients
      nevertheless satisfy universal laws satisfied by dense ordinary fluids: the
      Stokes-Einstein relation, the Arrhenius law of viscosity, and several excess
      entropy scaling relations. These results extend to long-range interaction
      potentials, the unifying description of atomic transport in condensed matter.

PMID- 16606004
TI  - Anisotropic system of quasiparticles in superfluid helium.
AB  - The thermodynamic properties of anisotropic quasiparticle systems of He II are
      considered for all degrees of anisotropy. It is shown that the thermodynamic
      functions of a strongly anisotropic phonon-roton system are mainly determined by
      rotons at all temperatures. Analytical expressions for the roton thermodynamic
      functions are obtained for all degrees of anisotropy. The maximum anisotropy is
      limited by the criterion for thermodynamic stability, which is here derived for
      the whole temperature range.

PMID- 16606005
TI  - Breaking of chiral symmetry and spontaneous rotation in a spinor Bose-Einstein
      condensate.
AB  - We show that a spin-1 Bose-Einstein condensate with ferromagnetic interactions
      spontaneously generates a topological spin texture, in which the m = +/- 1
      components of the magnetic sublevels form vortices with opposite circulations.
      This phenomenon originates from an interplay between ferromagnetic interactions
      and spin conservation.

PMID- 16606006
TI  - Stability of quantum breathers.
AB  - Using two methods we show that a quantized discrete breather in a 1D lattice is
      stable. One method uses path integrals and compares correlations for a (linear)
      local mode with those of the quantum breather. The other takes a local mode as
      the zeroth order system relative to which numerical, cutoff-insensitive
      diagonalization of the Hamiltonian is performed.

PMID- 16606007
TI  - Shock-induced structural phase transition, plasticity, and brittle cracks in
      aluminum nitride ceramic.
AB  - Atomistic mechanisms of fracture accompanying structural phase transformation
      (SPT) in AlN ceramic under hypervelocity impact are investigated using a 209 x
      10(6) atom molecular-dynamics simulation. The shock wave generated by the impact
      splits into an elastic wave and a slower SPT wave that transforms the wurtzite
      structure into the rocksalt phase. The interaction between the reflected elastic
      wave and the SPT wave front generates nanovoids and dislocations into the
      wurtzite phase. Nanovoids coalesce into mode I cracks while dislocations give
      rise to kink bands and mode II cracking.

PMID- 16606008
TI  - Anomalous latent heat in nonequilibrium phase transitions.
AB  - We study first-order phase transitions in a two-temperature system, where due to
      the time-scale separation all the basic thermodynamical quantities (free energy,
      entropy, etc.) are well defined. The sign of the latent heat is found to be
      counterintuitive: it is positive when going from the phase where the temperatures
      and the entropy are higher to the one where these quantities are lower. The
      effect exists only out of equilibrium and requires conflicting interactions. It
      is displayed on a lattice gas model of ferromagnetically interacting spin-1/2
      particles.

PMID- 16606009
TI  - Glassy behavior of light.
AB  - We study the nonlinear dynamics of a multimode random laser using the methods of
      statistical physics of disordered systems. A replica-symmetry breaking phase
      transition is predicted as a function of the pump intensity. We thus show that
      light propagating in a random nonlinear medium displays glassy behavior; i.e.,
      the photon gas has a multitude of metastable states and a nonvanishing
      complexity, corresponding to mode-locking processes in random lasers. The present
      work reveals the existence of new physical phenomena, and demonstrates how
      nonlinear optics and random lasers can be a benchmark for the modern theory of
      complex systems and glasses.

PMID- 16606010
TI  - Anomalous ion accelerated bulk diffusion of interstitial nitrogen.
AB  - Interstitial N diffusion under low energy (approximately 700 eV) Ar+ bombardment
      at 673 K in ion beam nitrided austenitic stainless steel is investigated. Ar+ ion
      bombardment increases the N mobility in depths far beyond the ion penetration
      depth, resulting in an increased broadening of the N depth profile as a function
      of Ar+ flux. This effect cannot be explained by any established mechanism of
      radiation-enhanced diffusion. An explanation based on quasiparticle-enhanced
      mobility is proposed.

PMID- 16606011
TI  - Large slip of aqueous liquid flow over a nanoengineered superhydrophobic surface.
AB  - While many recent studies have confirmed the existence of liquid slip over
      certain solid surfaces, there has not been a deliberate effort to design and
      fabricate a surface that would maximize the slip under practical conditions.
      Here, we have engineered a nanostructured superhydrophobic surface that minimizes
      the liquid-solid contact area so that the liquid flows predominantly over a layer
      of air. Measured through a cone-and-plate rheometer system, the surface has
      demonstrated dramatic slip effects: a slip length of approximately 20 microm for
      water flow and approximately 50 microm for 30 wt % glycerin. The essential
      geometrical characteristics lie with the nanoposts populated on the surface: tall
      and slender (i.e., needlelike) profile and submicron periodicity (i.e., pitch).

PMID- 16606012
TI  - Less strain energy despite fewer misfit dislocations: the impact of ordering.
AB  - The average strain state of Ge films grown on Si(111) by surfactant mediated
      epitaxy has been compared to the ordering of the interfacial misfit dislocation
      network. Surprisingly, a smaller degree of average lattice relaxation was found
      in films grown at higher temperature. On the other hand, these films exhibit a
      better ordered dislocation network. This effect energetically compensates the
      higher strain at higher growth temperature, leading to the conclusion that, apart
      from the formation of misfit dislocations, their ordering represents an important
      channel for lattice-strain energy relaxation.

PMID- 16606013
TI  - Graphitic nanofilms as precursors to wurtzite films: theory.
AB  - Periodic ab initio density functional calculations on ultrathin films of AlN,
      BeO, GaN, SiC, ZnO, and ZnS demonstrate the stabilization of thicker films
      terminating with the polar {0001} surface via charge transfer and metallization
      of the surface layers. In contrast thinner films remove the dipole by adopting a
      graphiticlike structure in which the atoms are threefold coordinate. This
      structure is thermodynamically the most favorable for these thinner films.
      Implications for the crystal growth of wurtzite materials are discussed.

PMID- 16606014
TI  - Critical adsorption of polyelectrolytes onto charged spherical colloids.
AB  - The adsorption of a flexible polyelectrolyte in a salt solution onto an
      oppositely charged spherical surface is investigated. An analytical solution is
      derived, which is valid for any sphere radius and consistently recovers the
      result of a planar surface in the limit of large sphere radii, by substituting
      the Debye-Huckel potential via the Hulthen potential. Expressions for critical
      quantities such as the critical radius and the critical surface charge density
      are provide. A comparison of our theoretical results with experiments and
      computer simulations yields remarkable good agreement.

PMID- 16606015
TI  - Self-assembly of gradient concentric rings via solvent evaporation from a
      capillary bridge.
AB  - A drop of solution containing nonvolatile solute is allowed to evaporate from a
      sphere-on-flat geometry. Left behind is a striking pattern of gradient concentric
      rings with unprecedented regularity. The center-to-center distance between
      adjacent rings, lambda(C-C), and the height of the ring, h(d), are strongly
      affected by the concentration of the solution and the properties of the solvent.
      The nature of the formation of regular gradient ring patterns during the course
      of irreversible solvent evaporation is revealed through theoretical calculations
      based on the mass conservation of the solution.

PMID- 16606016
TI  - Molecular recoiling in polymer thin film dewetting.
AB  - The molecular recoiling force stemming from nonequilibrium chain conformation was
      found to play a very important role in the dewetting stability of polymer thin
      films. Correct measurements and inclusion of this molecular force into
      thermodynamic consideration are crucial for analyzing dewetting phenomena and
      nanoscale polymer chain physics. This force was measured using a simple method
      based on contour relaxation at the incipient dewetting holes. The recoiling
      stress was found to increase dramatically with molecular weight and decreasing
      film thickness. The corresponding forces were calculated to be in the range from
      9.0 to 28.2 mN/m, too large to be neglected when compared to the dispersive
      forces (approximately 10 mN/m) commonly operative in thin polymer films.

PMID- 16606017
TI  - Transition metal oxides: extra thermodynamic stability as thin films.
AB  - The oxides of many transition metals wet their own metal surface. The adhesion
      energy at this interface (E(adh,ox/m)) provides extra stabilization, which lowers
      the O2 pressure required for oxide stability as a thin film below that required
      for bulk-oxide stability by the factor exp[(2gamma(g/ox) -
      E(adh,ox/m))/(tN(ox)RT)], where gamma(g/ox) is the surface energy of the oxide, t
      is the oxide film thickness, and N(ox) is the oxygen concentration in the bulk
      oxide (moles O2 per volume). For oxide films only approximately 1 nm thick, this
      correction can be many orders of magnitude. This may extend to other compounds.

PMID- 16606018
TI  - Formation and splitting of paired hydroxyl groups on reduced TiO2(110).
AB  - A combination of high-resolution scanning tunneling microscopy and density
      functional theory is utilized to study the interaction of water with the reduced
      TiO2(110)-(1 x 1) surface. As the direct product of water dissociation in oxygen
      vacancies, paired hydroxyl groups are formed. These pairs are immobile and stable
      unless they interact with adsorbed water molecules. As a result of these
      interactions, protons are transferred to adjacent oxygen rows, thereby forming
      single hydroxyl groups. Additionally, we show that hydroxyl groups facilitate the
      diffusion of water molecules over the oxygen rows.

PMID- 16606020
TI  - The alpha-gamma transition of cerium is entropy driven.
AB  - We emphasize, on the basis of experimental data and theoretical calculations,
      that the entropic stabilization of the gamma phase is the main driving force of
      the alpha-gamma transition of cerium in a wide temperature range below the
      critical point. Using a formulation of the total energy as a functional of the
      local density and of the f-orbital local Green's functions, we perform dynamical
      mean-field theory calculations within a new implementation based on the multiple
      linear muffin tin orbital (LMTO) method, which allows us to include semicore
      states. Our results are consistent with the experimental energy differences and
      with the qualitative picture of an entropy-driven transition, while also
      confirming the appearance of a stabilization energy of the alpha phase as the
      quasiparticle Kondo resonance develops.

PMID- 16606019
TI  - Controlling planar and vertical ordering in three-dimensional (In,Ga)As quantum
      dot lattices by GaAs surface orientation.
AB  - Anisotropic surface diffusion and strain are used to explain the formation of
      three-dimensional (In,Ga)As quantum dot lattices. The diffusion characteristics
      of the surface, coupled with the elastic anisotropy of the matrix, provides an
      excellent opportunity to influence the dot positions. In particular, quantum dots
      that are laterally organized into long chains or chessboard two-dimensional
      arrays vertically organized with strict vertical ordering or vertical ordering
      that is inclined to the sample surface normal are accurately predicted and
      observed.

PMID- 16606021
TI  - Probing semiconductor gap states with resonant tunneling.
AB  - Tunneling transport through the depletion layer under a GaAs {110} surface is
      studied with a low temperature scanning tunneling microscope (STM). The observed
      negative differential conductivity is due to a resonant enhancement of the
      tunneling probability through the depletion layer mediated by individual shallow
      acceptors. The STM experiment probes, for appropriate bias voltages, evanescent
      states in the GaAs band gap. Energetically and spatially resolved spectra show
      that the pronounced anisotropic contrast pattern of shallow acceptors occurs
      exclusively for this specific transport channel. Our findings suggest that the
      complex band structure causes the observed anisotropies connected with the zinc
      blende symmetry.

PMID- 16606022
TI  - Exact transformation for spin-charge separation of spin-1/2 fermions without
      constraints.
AB  - We demonstrate an exact local transformation which maps a purely Fermionic many
      body system to a system of spinful bosons and spinless fermions, demonstrating a
      possible path to a non-Fermi-liquid state. We apply this to the half-filled
      Hubbard model and show how the transformation maps the ordinary spin half
      Fermionic degrees of freedom exactly and without introducing Hilbert space
      constraints to a chargelike quasicharge fermion and a spinlike quasispin Boson
      while preserving all the symmetries of the model. We present approximate
      solutions with localized charge which emerge naturally from the Hubbard model in
      this form. Our results strongly suggest that charge tends to remain localized for
      large values of the Hubbard U.

PMID- 16606023
TI  - Thermodynamics and excitations of condensed polaritons in disordered
      microcavities.
AB  - We study the thermodynamic condensation of microcavity polaritons using a
      realistic model of disorder in semiconductor quantum wells. This approach
      correctly describes the polariton inhomogeneous broadening in the low density
      limit, and treats scattering by disorder to all orders in the condensed regime.
      While the weak disorder changes the thermodynamic properties of the transition
      little, the effects of disorder in the condensed state are prominent in the
      excitations and can be seen in resonant Rayleigh scattering.

PMID- 16606024
TI  - Consistency in formulation of spin current and torque associated with a variance
      of angular momentum.
AB  - Based on the Noether's theorem, we develop systematically and rigorously the spin
      dependent formulation of the conservation laws. The effect of the electronic
      polarization due to the spin-orbit coupling is included in the Maxwell equations.
      The polarization is related to the antisymmetric components of spin current, and
      it provides a possibility to measure the spin current directly. The variances of
      spin and orbit angular momentum currents imply a torque on the "electric dipole"
      associated with the moving electron. The dependencies of the torque on the
      polarization and the force on the motions of spin-polarized electrons in a two
      dimensional electron gas with the Rashba spin-orbit coupling are discussed.

PMID- 16606025
TI  - Tunneling and nonuniversality in continuum percolation systems.
AB  - The values obtained experimentally for the conductivity critical exponent in
      numerous percolation systems, in which the interparticle conduction is by
      tunneling, were found to be in the range of t0 and about t0 + 10, where t0 is the
      universal conductivity exponent. These latter values are, however, considerably
      smaller than those predicted by the available "one-dimensional"-like theory of
      tunneling percolation. In this Letter, we show that this long-standing
      discrepancy can be resolved by considering the more realistic "three-dimensional"
      model and the limited proximity to the percolation threshold in all the many
      available experimental studies.

PMID- 16606026
TI  - Dynamics of localized spins coupled to the conduction electrons with charge and
      spin currents.
AB  - The dynamics of the localized spins coupled to the conduction electrons is
      studied theoretically in the wide range of magnitudes of the charge and spin
      currents including the regime which has never been explored but is now possible
      in terms of the pure spin-current injection methods, e.g., the spin Hall effect
      and spin battery. The equations of motion for the two-spin system are
      investigated in detail, and its phase diagram of the dynamics is presented. It is
      found that the dynamics depends sensitively upon the relative magnitudes of the
      charge and spin currents; i.e., it shows steady state, periodic motion, and even
      chaotic behavior. The extension to the multispin system and its implications
      including a possible "spin-current detector" are also discussed.

PMID- 16606027
TI  - Charging mechanisms of trapped element-selectively excited nanoparticles exposed
      to soft x rays.
AB  - Charging mechanisms of trapped, element-selectively excited free SiO2
      nanoparticles by soft x rays are reported. The absolute charge state of the
      particles is measured and the electron emission probability is derived. Changes
      in electron emission processes as a function of photon energy and particle charge
      are obtained from the charging current. This allows us to distinguish
      contributions from primary photoelectrons, Auger electrons, and secondary
      electrons. Processes leading to no change in charge state after absorption of x
      ray photons are identified. O 1s-excited SiO2 particles of low charge state
      indicate that the charging current follows the inner-shell absorption. In
      contrast, highly charged SiO2 nanoparticles are efficiently charged by resonant
      Auger processes, whereas direct photoemission and normal Auger processes do not
      contribute to changes in particle charge. These results are discussed in terms of
      an electrostatic model.

PMID- 16606028
TI  - Transport properties of strongly correlated electrons in quantum dots studied
      with a simple circuit model.
AB  - Numerical calculations are shown to reproduce the main results of recent
      experiments involving nonlocal spin control in quantum dots [Craig, Science 304,
      565 (2004).]. In particular, the experimentally reported zero-bias-peak splitting
      is clearly observed in our studies. To understand these results, a simple
      "circuit model" is introduced and shown to qualitatively describe the
      experiments. The main idea is that the splitting originates in a Fano
      antiresonance, which is caused by having one quantum dot side connected in
      relation to the current's path. This scenario provides an explanation of the
      results of Craig et al. that is an alternative to the RKKY proposal, also
      addressed here.

PMID- 16606029
TI  - Two-electron linear intersubband light absorption in a biased quantum well.
AB  - We point out a novel manifestation of many-body correlations in the linear
      optical response of electrons confined in a quantum well. Namely, we demonstrate
      that along with the conventional absorption peak at a frequency omega close to
      the intersubband energy delta, there exists an additional peak at frequency h
      omega approximately = 2delta. This new peak is solely due to electron-electron
      interactions, and can be understood as excitation of two electrons by a single
      photon. The actual peak line shape is comprised of a sharp feature, due to
      excitation of pairs of intersubband plasmons, on top of a broader band due to
      absorption by two single-particle excitations. The two-plasmon contribution
      allows us to infer intersubband plasmon dispersion from linear absorption
      experiments.

PMID- 16606030
TI  - Semiclassical theory of chaotic conductors.
AB  - We calculate the Landauer conductance through chaotic ballistic devices in the
      semiclassical limit, to all orders in the inverse number of scattering channels
      without and with a magnetic field. Families of pairs of entrance-to-exit
      trajectories contribute, similarly to the pairs of periodic orbits making up the
      small-time expansion of the spectral form factor of chaotic dynamics. As a clue
      to the exact result we find that close self-encounters slightly hinder the escape
      of trajectories into leads. Our result explains why the energy-averaged
      conductance of individual chaotic cavities, with disorder or "clean," agrees with
      predictions of random-matrix theory.

PMID- 16606031
TI  - Interplay of spin and charge channels in zero-dimensional systems.
AB  - We study the interplay of charge and spin (zero-mode) channels in quantum dots.
      The latter affects the former in the form of a distinct signature on the
      differential conductance. We also obtain both longitudinal and transverse spin
      susceptibilities. All these observables, underlain by spin fluctuations, become
      accentuated as one approaches the Stoner instability. The nonperturbative effects
      of zero-mode interaction are described in terms of the propagation of gauge
      bosons associated with charge [U(1)] and spin [SU(2)] fluctuations in the dot,
      while transverse spin fluctuations are analyzed perturbatively.

PMID- 16606032
TI  - Parity of the pairing bosons in a high-temperature Pb-Bi2Sr2CaCu2O8 bilayer
      superconductor by angle-resolved photoemission spectroscopy.
AB  - We report the observation of a novel effect in the bilayer Pb-Bi2Sr2CaCu2O8 (Pb
      Bi2212) high-T(c) superconductor by means of angle-resolved photoemission with
      circularly polarized excitation. Different scattering rates, determined as a
      function of energy separately for the bonding and antibonding copper-oxygen
      bands, strongly imply that the dominating scattering channel is odd with respect
      to layer exchange within a bilayer. This is inconsistent with a phonon-mediated
      scattering and favors the participation of the odd collective spin excitations in
      the scattering mechanism in near-nodal regions of the k space, suggesting a
      magnetic nature of the pairing mediator.

PMID- 16606033
TI  - Nernst effect and disorder in the normal state of high-T(c) cuprates.
AB  - We have studied the influence of disorder induced by electron irradiation on the
      Nernst effect in optimally and underdoped YBa2Cu3O(7-delta) single crystals. The
      fluctuation regime above T(c) expands significantly with disorder, indicating
      that the T(c) decrease is partly due to the induced loss of phase coherence. In
      pure crystals the temperature extension of the Nernst signal is found to be
      narrow whatever the hole doping, contrary to data reported in the low-T(c)
      cuprate families. Our results show that the presence of intrinsic disorder can
      explain the enhanced range of the Nernst signal found in the pseudogap phase of
      the latter compounds.

PMID- 16606034
TI  - Controllable coupling between flux qubits.
AB  - We propose an experimentally realizable method to control the coupling between
      two flux qubits. In our proposal, the bias fluxes are always fixed for these two
      inductively coupled qubits. The detuning of these two qubits can be initially
      chosen to be sufficiently large, so that their initial interbit coupling is
      almost negligible. When a variable frequency or time-dependent magnetic flux
      (TDMF) is applied to one of the qubits, a well-chosen frequency of the TDMF can
      be used to compensate the initial detuning and to couple two qubits. This
      proposed method avoids fast changes of either qubit frequencies or the amplitudes
      of the bias magnetic fluxes through the qubit loops, and also offers a remarkable
      way to implement any logic gate, as well as tomographically measure flux qubit
      states.

PMID- 16606035
TI  - Field- and pressure-induced phases in Sr4Ru3O10: a spectroscopic investigation.
AB  - We have investigated the magnetic-field- and pressure-induced structural and
      magnetic phases of the triple-layer ruthenate Sr4Ru3O10. Magnetic-field-induced
      changes in the phonon spectra reveal dramatic spin-reorientation transitions and
      strong magnetoelastic coupling in this material. Further, we are able to deduce
      key magnetoelastic coupling parameters, and evidence that the magnetic moments
      are localized on the Ru sites. Additionally, pressure-dependent Raman
      measurements at different temperatures reveal an anomalous negative Gruneisen
      parameter associated with the B(1g) mode (approximately 380 cm(-1)) at low
      temperatures (T < 75 K), which can be explained consistently with the field
      dependent Raman data.

PMID- 16606036
TI  - Elastic scattering susceptibility of the high temperature superconductor
      Bi2Sr2CaCu2O(8+delta): a comparison between real and momentum space photoemission
      spectroscopies.
AB  - The joint density of states of Bi2Sr2CaCu2O(8+delta) is calculated by evaluating
      the autocorrelation of the single particle spectral function A(k, omega) measured
      from angle resolved photoemission spectroscopy (ARPES). These results are
      compared with Fourier transformed (FT) conductance modulations measured by
      scanning tunneling microscopy (STM). Good agreement between the two experimental
      probes is found for two different doping values examined. In addition, by
      comparing the FT-STM results to the autocorrelated ARPES spectra with different
      photon polarization, new insight on the form of the STM matrix elements is
      obtained. This shines new light on unsolved mysteries in the tunneling data.

PMID- 16606037
TI  - Exchange bias training effect in coupled all ferromagnetic bilayer structures.
AB  - Exchange coupled bilayers of soft and hard ferromagnetic thin films show
      remarkable analogies to conventional antiferromagnetic/ferromagnetic exchange
      bias heterostructures. Not only do all these ferromagnetic bilayers exhibit a
      tunable exchange bias effect, they also show a distinct training behavior upon
      cycling the soft layer through consecutive hysteresis loops. In contrast with
      conventional exchange bias systems, such all ferromagnetic bilayer structures
      allow the observation of training induced changes in the bias-setting
      hardmagnetic layer by means of simple magnetometry. Our experiments show
      unambiguously that the exchange bias training effect is driven by deviations from
      equilibrium in the pinning layer. A comparison of our experimental data with
      predictions from a theory based upon triggered relaxation phenomena shows
      excellent agreement.

PMID- 16606038
TI  - Transport in almost integrable models: perturbed Heisenberg chains.
AB  - The heat conductivity kappa(T) of integrable models, like the one-dimensional
      spin-1/2 nearest-neighbor Heisenberg model, is infinite even at finite
      temperatures as a consequence of the conservation laws associated with
      integrability. Small perturbations lead to finite but large transport
      coefficients which we calculate perturbatively using exact diagonalization and
      moment expansions. We show that there are two different classes of perturbations.
      While an interchain coupling of strength J(perpendicular) leads to kappa(T)
      proportional to 1/J(perpendicular)2 as expected from simple golden-rule
      arguments, we obtain a much larger kappa(T) proportional to 1/J'4 for a weak next
      nearest-neighbor interaction J'. This can be explained by a new approximate
      conservation law of the J-J' Heisenberg chain.

PMID- 16606039
TI  - Electronic structure of charge- and spin-controlled Sr(1-(x+y))La(x+y)Ti(1
      x)Cr(x)O3.
AB  - We present the electronic structure of Sr(1-(x+y))La(x+y)Ti(1-x)Cr(x)O3
      investigated by high-resolution photoemission spectroscopy. In the vicinity of
      the Fermi level, it was found that the electronic structure was composed of a Cr
      3d local state with the t(2g)3 configuration and a Ti 3d itinerant state. The
      energy levels of these Cr and Ti 3d states are well interpreted by the difference
      of the charge-transfer energy of both ions. The spectral weight of the Cr 3d
      state is completely proportional to the spin concentration x irrespective of the
      carrier concentration y, indicating that the spin density can be controlled by x
      as desired. In contrast, the spectral weight of the Ti 3d state is not
      proportional to y, depending on the amount of Cr doping.

PMID- 16606040
TI  - Effect of spin-orbit interaction on a magnetic impurity in the vicinity of a
      surface.
AB  - We propose a new mechanism for surface-induced magnetic anisotropy to explain the
      thickness dependence of the Kondo resistivity of thin films of dilute magnetic
      alloys. The surface anisotropy energy, generated by spin-orbit coupling on the
      magnetic impurity itself, is an oscillating function of the distance d from the
      surface and decays as 1/d2. Numerical estimates based on simple models suggest
      that this mechanism, unlike its alternatives, gives rise to an effect of the
      desired order of magnitude.

PMID- 16606041
TI  - Magnetic vortex core dynamics in cylindrical ferromagnetic dots.
AB  - We report direct imaging by means of x-ray photoemission electron microscopy of
      the dynamics of magnetic vortices confined in micron-sized circular permalloy
      dots that are 30 nm thick. The vortex core positions oscillate on a 10 ns time
      scale in a self-induced magnetostatic potential well after the in-plane magnetic
      field is turned off. The measured oscillation frequencies as a function of the
      aspect ratio of the dots are in agreement with theoretical calculations presented
      for the same geometry.

PMID- 16606042
TI  - Direct observation of exchange bias related uncompensated spins at the CoO/Cu
      interface.
AB  - Magnetization-induced optical second harmonic generation (MSHG) from the exchange
      biased CoO/Cu-(X)/Fe multilayer shows the presence of pinned uncompensated spins
      at the CoO/Cu interface. For increasing Cu spacer thickness, the exchange bias
      measured via the hysteresis loop shift diminishes and disappears at X = 3.5 nm,
      while the MSHG signal still shows a strong magnetic contribution from the CoO
      interface. This indicates that the magnetic interaction between Fe and CoO layers
      is sufficiently strong to induce order in the antiferromagnetic layer even at a
      spacer thickness for which there is no observable hysteresis loop shift.

PMID- 16606043
TI  - Training effect in an exchange bias system: the role of interfacial domain walls.
AB  - Polarized neutron reflectivity (PNR) is used to obtain the magnetic depth profile
      of an antiferromagnetically coupled ferrimagnetic/ferrimagnetic bilayer,
      Gd40Fe60/Tb12Fe88. This system shows a transition from positive to negative
      exchange bias field H(E) as the cooling field H(cf) is increased from small to
      large positive value. It also exhibits training behavior upon field cycling which
      affects H(E) and the coercive field H(C). From the PNR measurements at room
      temperature and at 15 K, we confirm that the magnetic configuration inside the
      TbFe layer is frozen when the sample is cooled in various H(cf). The thickness
      and pitch of the magnetic twist inside the TbFe layer depend on H(cf) and give
      rise to the observed differences in the bias field. Irreversible reorganization
      of the TbFe magnetization at the interface occurs upon GdFe magnetization
      reversal and is found to explain the training effect as well as the overall
      reduction in coercivity.

PMID- 16606044
TI  - Mapping the Monte Carlo scheme to Langevin dynamics: a Fokker-Planck approach.
AB  - We propose a general method of using the Fokker-Planck equation (FPE) to link the
      Monte Carlo (MC) and the Langevin micromagnetic schemes. We derive the drift and
      diffusion FPE terms corresponding to the MC method and show that it is
      analytically equivalent to the stochastic Landau-Lifshitz-Gilbert (LLG) equation
      of Langevin-based micromagnetics. Subsequent results such as the time
      quantification factor for the Metropolis MC method can be rigorously derived from
      this mapping equivalence. The validity of the mapping is shown by the close
      numerical convergence between the MC method and the LLG equation for the case of
      a single magnetic particle as well as interacting arrays of particles. We also
      find that our Metropolis MC method is accurate for a large range of damping
      factors alpha, unlike previous time-quantified MC methods which break down at low
      alpha, where precessional motion dominates.

PMID- 16606045
TI  - Stimulated emission from the biexciton in a single self-assembled II-VI quantum
      dot.
AB  - Using two-photon excitation, stimulated emission from the biexciton state in a
      single CdSe/ZnSe quantum dot is observed in a two-pulse configuration. We
      directly time resolve the emission-absorption characteristics and verify the
      potential for laser action. By setting the polarization of the stimulation pulse,
      the recombination path of the biexciton and, by this, the state of the photons
      emitted in the decay cascade is controlled. We elaborate also the coherent
      response and address entanglement and disentanglement of the exciton-biexciton
      system.

PMID- 16606046
TI  - Resonant inelastic x-ray scattering at the oxygen K resonance of NiO: nonlocal
      charge transfer and double-singlet excitations.
AB  - We report high-resolution polarization-dependent resonant inelastic x-ray
      scattering (RIXS) at the O K resonance of NiO showing a rich excitation spectrum.
      We perform multisite Ni6O19 cluster model calculations, revealing that solid
      state effects are substantial. We identify a nonlocal charge transfer excitation
      at 4-5 eV and double-singlet creation at 1.75 eV, both exhibiting significant
      scattering geometry dependence. Apart from an intense band of local charge
      transfer excitations (above 5 eV) also dd excitations at 1 eV are observed.
      Finally, we point out that O K RIXS of correlated metal oxides allows a
      quantitative and consistent determination of the charge transfer energy delta and
      the Hund coupling energy J(H).

PMID- 16606047
TI  - Ferroelectricity in spiral magnets.
AB  - It was recently observed that the ferroelectrics showing the strongest
      sensitivity to an applied magnetic field are spiral magnets. We present a
      phenomenological theory of inhomogeneous ferroelectric magnets, which describes
      their thermodynamics and magnetic field behavior, e.g., dielectric susceptibility
      anomalies at magnetic transitions and sudden flops of electric polarization in an
      applied magnetic field. We show that electric polarization can also be induced at
      domain walls and that magnetic vortices carry electric charge.

PMID- 16606048
TI  - Optical pump-probe measurements of local nuclear spin coherence in semiconductor
      quantum wells.
AB  - We demonstrate local manipulation and detection of nuclear spin coherence in
      semiconductor quantum wells by an optical pump-probe technique combined with
      pulse rf NMR. The Larmor precession of photoexcited electron spins is monitored
      by time-resolved Kerr rotation (TRKR) as a measure of nuclear magnetic field.
      Under the irradiation of resonant pulsed rf magnetic fields, Rabi oscillations of
      nuclear spins are traced by TRKR signals. The intrinsic coherence time evaluated
      by a spin-echo technique reveals the dependence on the orientation of the
      magnetic field with respect to the crystalline axis as expected by the nearest
      neighbor dipole-dipole interaction.

PMID- 16606049
TI  - Structure of dense liquid water by neutron scattering to 6.5 GPa and 670 K.
AB  - We present a neutron diffraction study of liquid water to 6.5 GPa and 670 K. From
      the measured structure factors we determine radial and angular distributions. It
      is shown that with increasing density water approaches a local structure common
      to a simple liquid while distorting only a little the tetrahedral first-neighbor
      coordination imposed by hydrogen bonds that remain intact.

PMID- 16606050
TI  - Electric-field-induced chirality flipping in smectic liquid crystals: the role of
      anisotropic viscosity.
AB  - We demonstrate the homogeneous and permanent reversal of the chirality of a
      condensed phase by an applied electric field. Tilted chiral smectic layers
      exhibit a coupled polarization density and molecular orientation fields which
      reorient about the layer normal as couple of fixed handedness in response to
      small applied electric fields. Experiments on some bent-core smectics show that
      above a threshold field the induced rotation can occur instead about the
      molecular long axis and that, as a result, the handedness of the phase can be
      flipped. The effect is quantitatively described by a nonequilibrium dissipative
      model of chiral smectic dynamics with anisotropic rotational viscosities.

PMID- 16606051
TI  - Propulsion with a rotating elastic nanorod.
AB  - The dynamics of a rotating elastic filament is investigated using Stokesian
      simulations. The filament, straight and tilted with respect to its rotation axis
      for small driving torques, undergoes at a critical torque a strongly
      discontinuous shape bifurcation to a helical state. It induces a substantial
      forward propulsion whatever the sense of rotation: a nanomechanical force
      rectification device is established.

PMID- 16606052
TI  - Observation of bistability and hysteresis in optical binding of two dielectric
      spheres.
AB  - Using a dual-beam fiber optic trap, we have experimentally observed bistability
      and hysteresis in the equilibrium separations of a pair of optically bound
      dielectric spheres in one dimension. These observations are in agreement with our
      coupled system model in which the dielectric spheres modify the field
      propagation, and the field self-consistently determines the optical forces on the
      spheres. Our results reveal hitherto unsuspected complexity in the coupled light
      sphere system.

PMID- 16606053
TI  - Detecting electronic coherence in excited-state electron transfer in fluorinated
      benzenes.
AB  - Photoinduced electron transfer (ET) in heavily fluorinated benzenes in solution
      has been studied with broadband transient absorption spectroscopy. Spectrally
      resolved kinetics exhibit oscillations with amplitude up to 70% of the signal.
      The oscillation frequency is specific for each probe; in addition, for
      pentafluorobenzene it markedly depends on solvent, being 86 cm(-1) in hexane and
      94 cm(-1) in acetonitrile. We argue that the observed behavior is not related to
      vibrational coherences, but originate from coherent electronic motion between an
      optically excited and an ET state.

PMID- 16606054
TI  - Logarithmic chain-exchange kinetics of diblock copolymer micelles.
AB  - We present a study of equilibrium chain-exchange kinetics of a well-defined model
      system for starlike polymeric micelles. The results show that the kinetics
      follows a logarithmic time dependence. The same feature has been confirmed for
      two other micellar systems. This is in sharp contrast to theoretical predictions
      and hints towards strongly coupled chain dynamics within the micellar cores
      induced by geometrical constraints.

PMID- 16606055
TI  - Criticality and phase transition in stock-price fluctuations.
AB  - We analyze the behavior of the U.S. S&P 500 index from 1984 to 1995, and
      characterize the non-Gaussian probability density functions (PDF) of the log
      returns. The temporal dependence of fat tails in the PDF of a ten-minute log
      return shows a gradual, systematic increase in the probability of the appearance
      of large increments on approaching black Monday in October 1987, reminiscent of
      parameter tuning towards criticality. On the occurrence of the black Monday
      crash, this culminates in an abrupt transition of the scale dependence of the non
      Gaussian PDF towards scale-invariance characteristic of critical behavior. These
      facts suggest the need for revisiting the turbulent cascade paradigm recently
      proposed for modeling the underlying dynamics of the financial index, to account
      for time varying-phase transitionlike and scale invariant-critical-like behavior.

PMID- 16606056
TI  - Universal behavior of optimal paths in weighted networks with general disorder.
AB  - We study the statistics of the optimal path in both random and scale-free
      networks, where weights are taken from a general distribution P(w). We find that
      different types of disorder lead to the same universal behavior. Specifically, we
      find that a single parameter (S defined as AL(-1/v) for d-dimensional lattices,
      and S defined as AN(-1/3) for random networks) determines the distributions of
      the optimal path length, including both strong and weak disorder regimes. Here v
      is the percolation connectivity exponent, and A depends on the percolation
      threshold and P(w). We show that for a uniform P(w), Poisson or Gaussian, the
      crossover from weak to strong does not occur, and only weak disorder exists.

PMID- 16606057
TI  - Comment on "Novel public key encryption technique based on multiple chaotic
      systems".

PMID- 16606058
TI  - Comment on "Explanation of the inverse Doppler effect observed in nonlinear
      transmission lines".

PMID- 16606060
TI  - Comment on "Signature of a chemical bond in the conductance between two metal
      surfaces".

PMID- 16606062
TI  - Maximum confidence quantum measurements.
AB  - We consider the problem of discriminating between states of a specified set with
      maximum confidence. For a set of linearly independent states unambiguous
      discrimination is possible if we allow for the possibility of an inconclusive
      result. For linearly dependent sets an analogous measurement is one which allows
      us to be as confident as possible that when a given state is identified on the
      basis of the measurement result, it is indeed the correct state.

PMID- 16606063
TI  - Beyond linear response spectroscopy of ultracold fermi gases.
AB  - We study rf spectroscopy of ultracold Fermi gas by going beyond the linear
      response in the field-matter interaction. Higher order perturbation theory allows
      virtual processes and energy conservation beyond the single-particle level. We
      formulate an effective higher order theory, which agrees quantitatively with
      experiments on the pairing gap and is consistent with the absence of the mean
      field shift in the spin-flip experiment.

PMID- 16606064
TI  - Semiclassical propagator of the Wigner function.
AB  - Propagation of the Wigner function is studied on two levels of semiclassical
      propagation: one based on the Van Vleck propagator, the other on phase-space path
      integration. Leading quantum corrections to the classical Liouville propagator
      take the form of a time-dependent quantum spot. Its oscillatory structure depends
      on whether the underlying classical flow is elliptic or hyperbolic. It can be
      interpreted as the result of interference of a pair of classical trajectories,
      indicating how quantum coherences are to be propagated semiclassically in phase
      space. The phase-space path-integral approach allows for a finer resolution of
      the quantum spot in terms of Airy functions.

PMID- 16606065
TI  - Beam quality of a nonideal atom laser.
AB  - We study the propagation of a noninteracting atom laser distorted by the strong
      lensing effect of the Bose-Einstein condensate (BEC) from which it is outcoupled.
      We observe a transverse structure containing caustics that vary with the density
      within the residing BEC. Using the WKB approximation, Fresnel-Kirchhoff integral
      formalism, and ABCD matrices, we are able to describe analytically the atom-laser
      propagation. This allows us to characterize the quality of the nonideal atom
      laser beam by a generalized M2 factor defined in analogy to photon lasers.
      Finally we measure this quality factor for different lensing effects.

PMID- 16606066
TI  - Quantum key distribution based on arbitrarily weak distillable entangled states.
AB  - States with private correlations but little or no distillable entanglement were
      recently reported. Here, we consider the secure distribution of such states,
      i.e., the situation when an adversary gives two parties such states and they have
      to verify privacy. We present a protocol which enables the parties to extract
      from such untrusted states an arbitrarily long and secure key, even though the
      amount of distillable entanglement of the untrusted states can be arbitrarily
      small.

PMID- 16606067
TI  - Experimental quantum key distribution with decoy states.
AB  - To increase dramatically the distance and the secure key generation rate of
      quantum key distribution (QKD), the idea of quantum decoys--signals of different
      intensities--has recently been proposed. Here, we present the first experimental
      implementation of decoy state QKD. By making simple modifications to a commercial
      quantum key distribution system, we show that a secure key generation rate of 165
      bit/s, which is 1/4 of the theoretical limit, can be obtained over 15 km of a
      telecommunication fiber. We also show that with the same experimental parameters,
      not even a single bit of secure key can be extracted with a non-decoy-state
      protocol. Compared to building single photon sources, decoy state QKD is a much
      simpler method for increasing the distance and key generation rate of
      unconditionally secure QKD.

PMID- 16606068
TI  - Topological quantum computing with only one mobile quasiparticle.
AB  - In a topological quantum computer, universal quantum computation is performed by
      dragging quasiparticle excitations of certain two dimensional systems around each
      other to form braids of their world lines in 2 + 1 dimensional space-time. In
      this Letter we show that any such quantum computation that can be done by
      braiding n identical quasiparticles can also be done by moving a single
      quasiparticle around n - 1 other identical quasiparticles whose positions remain
      fixed.

PMID- 16606069
TI  - Fault-tolerant quantum communication based on solid-state photon emitters.
AB  - We describe a novel protocol for a quantum repeater that enables long-distance
      quantum communication through realistic, lossy photonic channels. Contrary to
      previous proposals, our protocol incorporates active purification of arbitrary
      errors at each step of the protocol using only two qubits at each repeater
      station. Because of these minimal physical requirements, the present protocol can
      be realized in simple physical systems such as solid-state single photon
      emitters. As an example, we show how nitrogen-vacancy color centers in diamond
      can be used to implement the protocol, using the nuclear and electronic spin to
      form the two qubits.

PMID- 16606070
TI  - Worm algorithm for continuous-space path integral monte carlo simulations.
AB  - We present a new approach to path integral Monte Carlo (PIMC) simulations based
      on the worm algorithm, originally developed for lattice models and extended here
      to continuous-space many-body systems. The scheme allows for efficient
      computation of thermodynamic properties, including winding numbers and off
      diagonal correlations, for systems of much greater size than that accessible to
      conventional PIMC simulations. As an illustrative application of the method, we
      simulate the superfluid transition of 4He in two dimensions.

PMID- 16606071
TI  - Smoothing of depinning transitions for directed polymers with quenched disorder.
AB  - We consider disordered models of pinning of directed polymers on a defect line,
      including (1 + 1)-dimensional interface wetting models, disordered Poland
      Scheraga models of DNA denaturation, and other (1 + d)-dimensional polymers in
      interaction with columnar defects. We consider also random copolymers at a
      selective interface. These models are known to have a (de)pinning transition at
      some critical line in the phase diagram. In this work we prove that, as soon as
      disorder is present, the transition is at least of second order: the free energy
      is differentiable at the critical line, and the order parameter (contact
      fraction) vanishes continuously at the transition. On the other hand, it is known
      that the corresponding nondisordered models can have a first order (de)pinning
      transition, with a jump in the order parameter. Our results confirm predictions
      based on the Harris criterion.

PMID- 16606072
TI  - Thermodynamics of a colloidal particle in a time-dependent nonharmonic potential.
AB  - We study the motion of an overdamped colloidal particle in a time-dependent
      nonharmonic potential. We demonstrate the first lawlike balance between applied
      work, exchanged heat, and internal energy on the level of a single trajectory.
      The observed distribution of applied work is distinctly non-Gaussian in good
      agreement with numerical calculations. Both the Jarzynski relation and a detailed
      fluctuation theorem are verified with good accuracy.

PMID- 16606073
TI  - Cosmological solutions in a spontaneously broken gauge theory.
AB  - We consider solutions of the Yang-Mills-Higgs system coupled to gravity in
      asymptotically de Sitter space-time. The basic features of two classes of
      solutions are discussed, one of them corresponding to magnetic monopoles, the
      other one to sphalerons. We find that although the total mass within the
      cosmological horizon of these configurations is finite, their mass evaluated at
      timelike infinity generically diverges for most values of the cosmological
      constant. Also, no solutions exist in the absence of a Higgs potential.

PMID- 16606074
TI  - Black hole particle emission in higher-dimensional spacetimes.
AB  - In models with extra dimensions, a black hole evaporates both in the bulk and on
      the visible brane, where standard model fields live. The exact emissivities of
      each particle species are needed to determine how the black hole decay proceeds.
      We compute and discuss the absorption cross sections, the relative emissivities,
      and the total power output of all known fields in the evaporation phase. Graviton
      emissivity is highly enhanced as the spacetime dimensionality increases.
      Therefore, a black hole loses a significant fraction of its mass in the bulk.
      This result has important consequences for the phenomenology of black holes in
      models with extra dimensions and black hole detection in particle colliders.

PMID- 16606075
TI  - Leptogenesis from spin-gravity coupling following inflation.
AB  - The energy levels of the left- and the right-handed neutrinos are split in the
      background of gravitational waves generated during inflation, which, in presence
      of lepton-number-violating interactions, gives rise to a net lepton asymmetry at
      equilibrium. Lepton number violation is achieved by the same dimension five
      operator which gives rise to neutrino masses after electroweak symmetry breaking.
      A net baryon asymmetry of the same magnitude can be generated from this lepton
      asymmetry by electroweak sphaleron processes.

PMID- 16606076
TI  - Precision microstate counting of small black rings.
AB  - We examine certain two-charge supersymmetric states with spin in five-dimensional
      string theories which can be viewed as small black rings when the gravitational
      coupling is large. Using the 4D-5D connection, these small black rings correspond
      to four-dimensional nonspinning small black holes. Using this correspondence, we
      compute the degeneracy of the microstates of the small black rings exactly and
      show that it is in precise agreement with the macroscopic degeneracy to all
      orders in an asymptotic expansion. Furthermore, we analyze the five-dimensional
      small black ring geometry and show qualitatively that the Regge bound arises from
      the requirement that closed timelike curves be absent.

PMID- 16606077
TI  - In-medium effects on phase space distributions of antikaons measured in proton
      nucleus collisions.
AB  - Differential production cross sections of K+/- mesons have been measured in p + C
      and p + Au collisions at 1.6, 2.5, and 3.5 GeV proton beam energy. At beam
      energies close to the production threshold, the K- multiplicity is strongly
      enhanced with respect to proton-proton collisions. According to microscopic
      transport calculations, this enhancement is caused by two effects: the
      strangeness exchange reaction NY --> K- NN and an attractive in-medium K- N
      potential at saturation density.

PMID- 16606078
TI  - Systematics of proton emission.
AB  - A very simple formula is presented that relates the logarithm of the half-life,
      corrected by the centrifugal barrier, with the Coulomb parameter in proton decay
      processes. The corresponding experimental data lie on two straight lines which
      appear as a result of a sudden change in the nuclear shape marking two regions of
      deformation independently of the angular momentum of the outgoing proton. This
      feature provides a powerful tool to assign experimentally quantum numbers in
      proton emitters.

PMID- 16606079
TI  - Predicting narrow states in the spectrum of a nucleus beyond the proton drip
      line.
AB  - Properties of particle-unstable nuclei lying beyond the proton drip line can be
      ascertained by considering the (usually known) properties of its mirror neutron
      rich system. We have used a multichannel algebraic scattering theory to map the
      known properties of the neutron-14C system to those of the proton-14O one from
      which we deduce that the particle-unstable 15F will have a spectrum of two low
      lying broad resonances of positive parity and, at higher excitation, three narrow
      negative-parity ones. A key feature is to use coupling to Pauli-hindered states
      in the target.

PMID- 16606080
TI  - Exact solution of the isovector neutron-proton pairing Hamiltonian.
AB  - The complete exact solution of the T = 1 neutron-proton pairing Hamiltonian is
      presented in the context of the SO(5) Richardson-Gaudin model with nondegenerate
      single-particle levels and including isospin symmetry-breaking terms. The power
      of the method is illustrated with a numerical calculation for for 64Ge for a pf +
      g9/2 model space which is out of reach of modern shell-model codes.

PMID- 16606081
TI  - Molecular frame photoelectron emission in the presence of autoionizing
      resonances.
AB  - We have measured the angular distribution of valence-shell photoelectrons excited
      by circularly polarized light from fixed-in-space N2O molecules, near to and on
      top of resonances due to Rydberg states embedded in the ionization continuum. The
      sign of the circular dichroism for ionization into the N2O+ (B2Pi, (1pi)-1) state
      is reversed on top of the lowest dominant resonances. Measured angular
      distributions are well predicted by state-of-the-art multichannel configuration
      interaction calculations. The change in sign of the circular dichroism at the
      peak of the resonance is the result of a rapid change in the phases of resonant
      dipole matrix elements by a factor of 2pi as the energy is scanned across the
      resonance.

PMID- 16606082
TI  - Coherent population transfer in an atom by multiphoton adiabatic rapid passage.
AB  - Coherent population transfer in an atom using a sequence of adiabatic rapid
      passages through single-photon resonances is well-known, but it requires that the
      frequency sweep match the changing frequencies of the atomic transitions. The
      same population transfer can be effected via a single multiphoton adiabatic rapid
      passage, which requires only a small frequency sweep, if it is possible to select
      the desired multiphoton transition from the many possible transitions. Here we
      report the observation of population transfer between Rydberg states by high
      order multiphoton adiabatic rapid passage.

PMID- 16606083
TI  - Observation of multichannel collisions of cold metastable calcium atoms.
AB  - Recent theoretical work indicates that collisions between metastable alkaline
      earth atoms (AEAs) in the presence of external magnetic fields should be largely
      determined by partial waves with large angular momenta even at very low
      temperatures. Unusually large inelastic collision cross sections were predicted
      and doubts have been raised regarding the feasibility of evaporative cooling of
      metastable AEAs in magnetic traps. Here we present experimental data for
      40Ca[4s4p]3 P2 clearly confirming the asserted multichannel character of the
      collision mechanism. While elastic cross sections are found to be similar to the
      predicted values, inelastic cross sections exceed the calculations by an order of
      magnitude. Our results substantiate the expectation of inefficient evaporative
      cooling.

PMID- 16606084
TI  - Attosecond pump probe: exploring ultrafast electron motion inside an atom.
AB  - The attosecond pump probe, in close analogy to the standard femtosecond probing
      technique, has been proposed and theoretically demonstrated with its application
      to explore ultrafast electron motions inside atoms. We have performed realistic
      modeling for the full dynamics of both the femtosecond pumping and the attosecond
      probing processes. Our simulations have illustrated that an ultrashort
      oscillation period of 2.0 fs can be mapped out for a wave packet in low-lying
      excited states of the helium atom. This opens the prospect of a wealth of similar
      pump probe experiments to examine ultrafast electronic or atomic motions.

PMID- 16606085
TI  - Asymptotics of the dispersion interaction: analytic benchmarks for van der Waals
      energy functionals.
AB  - We show that the usual sum of R-6 contributions from elements separated by
      distance R can give qualitatively wrong results for the electromagnetically
      nonretarded van der Waals interaction between nonoverlapping bodies. This occurs
      for anisotropic nanostructures that have a zero electronic energy gap, such as
      metallic nanotubes or nanowires, and nanolayered systems including metals and
      graphene planes. In all these cases our analytic microscopic calculations give an
      interaction falling off with a power of separation different from the
      conventional value. We discuss implications for van der Waals energy functionals.
      The new nanotube interaction might be directly observable at submicron
      separations.

PMID- 16606086
TI  - Simple method for obtaining electron scattering phase shifts from energies of an
      atom in a cavity.
AB  - We present a simple method for obtaining elastic scattering phase shifts and
      cross sections from precise ab initio many-body perturbation theory energies of
      atoms in variable cavities. This method does not require calculations of wave
      functions of continuum states, can be generalized to many atoms and ions, and is
      extremely convenient because existing codes developed for energy calculations can
      be used without modification. The high precision of the method and close
      agreement with experiment are illustrated on examples of e-Ar and e-Kr
      scattering. Correlations as well as relativistic corrections are systematically
      considered.

PMID- 16606087
TI  - Ortho-para transition rate in mu-molecular hydrogen and the proton's induced
      pseudoscalar coupling gp.
AB  - We report a measurement of the ortho-para transition rate in the p mu p molecule.
      The experiment was conducted at TRIUMF via the measurement of the time dependence
      of the 5.2 MeV neutrons from muon capture in liquid hydrogen. The measurement
      yielded an ortho-para rate Lambda op = (11.1 +/- 1.7 +/-(0.9)(0.6)) x 10(4) s(
      1), which is substantially larger than the earlier result of Bardin et al. The
      result has striking implications for the proton's induced pseudoscalar coupling
      g(p), changing the value of g(p) obtained from the most precise ordinary muon
      capture measurement from 10.6 +/- 2.7 to 0.8 +/- 2.8, and from the sole radiative
      muon capture measurement from 12.2 +/- 1.1 to 10.6 +/- 1.2, bringing the latter
      result closer to theoretical predictions.

PMID- 16606088
TI  - Quantum theory of light and noise polarization in nonlinear optics.
AB  - We present a consistent quantum theory of the electromagnetic field in
      nonlinearly responding causal media, with special emphasis on Chi(2) media.
      Starting from QED in linearly responding causal media, we develop a method to
      construct the cubic Hamiltonian expressed in terms of the complex nonlinear
      susceptibility in a quantum mechanically consistent way. In particular, we show
      that the method yields the nonlinear noise polarization, which together with the
      linear one is responsible for intrinsic quantum decoherence.

PMID- 16606089
TI  - Surface gap solitons.
AB  - We put forward the existence of surface gap solitons at the interface between
      uniform media and an optical lattice with defocusing nonlinearity. Such new type
      of solitons forms when the incident and reflected waves at the interface of the
      lattice experience Bragg scattering, and feature a combination of the unique
      properties of both surface waves and gap solitons. We discover that gap surface
      solitons exist only when the lattice depth exceeds a threshold value, that they
      can be made completely stable, and that they can form stable bound states.

PMID- 16606090
TI  - Experimental study of coherence vortices: local properties of phase singularities
      in a spatial coherence function.
AB  - By controlling the irradiance of an extended quasimonochromatic, spatially
      incoherent source, an optical field is generated that exhibits spatial coherence
      with phase singularities, called coherence vortices. A simple optical geometry
      for direct visualization of coherence vortices is proposed, and the local
      properties and the spatial evolution of coherence vortex are experimentally
      investigated. To our knowledge, this is the first direct and quantitative
      experimental measurement of a generic coherence vortex.

PMID- 16606091
TI  - Conservation of angular momentum, transverse shift, and spin Hall effect in
      reflection and refraction of an electromagnetic wave packet.
AB  - We present a solution to the problem of reflection and refraction of a polarized
      Gaussian beam on the interface between two transparent media. The transverse
      shifts of the beams' centers of gravity are calculated. They always satisfy the
      total angular momentum conservation law for beams, but, in general, do not
      satisfy the conservation laws for individual photons as a consequence of the lack
      of the "which path" information in a two-channel wave scattering. The field
      structure for the reflected and refracted beams is analyzed. In the scattering of
      a linearly polarized beam, photons of opposite helicities are accumulated at the
      opposite edges of the beam: this is the spin Hall effect for photons, which can
      be registered in the cross-polarized component of the scattered beam.

PMID- 16606092
TI  - Waveguide arrays as plasmonic metamaterials: transmission below cutoff.
AB  - Since the work of Ebbesen et al. [Nature (London) 391, 667 (1998)], there has
      been immense interest in the optical properties of subwavelength holes in metal
      layers. While the enhanced transmission observed is generally associated with
      surface plasmon polaritons (SPPs), theoretical predictions suggest a similar
      response with perfectly conducting materials. However, Pendry et al. [Science
      305, 847 (2004)] proposed that, if textured on a subwavelength scale, even
      perfect conductors support surface modes. Here, using microwave radiation
      incident upon an array of metal waveguides, we observe peaks in the
      transmissivity below cutoff and confirm the crucial role of these SPP-like modes
      in the mechanism responsible.

PMID- 16606093
TI  - Optically tunable photonic stop bands in homogeneous absorbing media.
AB  - Resonantly absorbing media supporting electromagnetically induced transparency
      may give rise to specific periodic patterns where a light probe is found to
      experience a fully developed photonic band gap yet with negligible absorption
      everywhere. In ultracold atomic samples the gap is found to arise from spatial
      regions where Autler-Townes splitting and electromagnetically induced
      transparency alternate with one another and detailed calculations show that
      accurate and efficient coherent optical control of the gap can be accomplished.
      The remarkable experimental simplicity of the control scheme would ease quantum
      nonlinear optics applications.

PMID- 16606094
TI  - Three-step model for high-harmonic generation in many-electron systems.
AB  - The three-step model (TSM) of high-harmonic generation (HHG) is generalized to
      atomic and molecular many-electron systems. Using many-body perturbation theory,
      corrections to the standard TSM due to exchange and electron-electron
      correlations are derived. It is shown that canonical Hartree-Fock orbitals
      represent the most appropriate set of one-electron states for calculating the HHG
      spectrum. To zeroth order in many-body perturbation theory, a HHG experiment
      allows direct access, in general, to a combination of occupied Hartree-Fock
      orbitals rather than to the highest occupied molecular orbital by itself.

PMID- 16606095
TI  - All-angle negative refraction for surface plasmon waves using a metal-dielectric
      metal structure.
AB  - We show that a metal-dielectric-metal structure can function as a negative
      refraction lens for surface plasmon waves on a metal surface. The structure is
      uniform with respect to a plane of incidence and operates at the optical
      frequency range. Using three-dimensional finite-difference time-domain
      simulations, we demonstrate the imaging operation of the structure with realistic
      material parameters including dispersions and losses. Our design should
      facilitate the demonstration of many novel effects associated with negative
      refraction on chip at optical wavelength ranges. In addition, this structure
      provides a new way of controlling the propagation of surface plasmons, which are
      important for nanoscale manipulation of optical waves.

PMID- 16606096
TI  - Universal features of hydrodynamic Lyapunov modes in extended systems with
      continuous symmetries.
AB  - Numerical and analytical evidence is presented to show that hydrodynamic Lyapunov
      modes (HLMs) do exist in lattices of coupled Hamiltonian and dissipative maps.
      More importantly, we find that HLMs in these two classes of systems are different
      with respect to their spatial structure and their dynamical behavior. To be
      concrete, the corresponding dispersion relations of Lyapunov exponent versus wave
      number are characterized by lambda approximately k and lambda approximately k2,
      respectively. The HLMs in Hamiltonian systems are propagating, whereas those of
      dissipative systems show only diffusive motion. Extensive numerical simulations
      of various systems confirm that the existence of HLMs is a very general feature
      of extended dynamical systems with continuous symmetries and that the above
      mentioned differences between the two classes of systems are universal in large
      extent.

PMID- 16606097
TI  - Defect chaos and bursts: hexagonal rotating convection and the complex Ginzburg
      Landau equation.
AB  - We employ numerical computations of the full Navier-Stokes equations to
      investigate non-Boussinesq convection in a rotating system using water as the
      working fluid. We identify two regimes. For weak non-Boussinesq effects the Hopf
      bifurcation from steady to oscillating (whirling) hexagons is supercritical and
      typical states exhibit defect chaos that is systematically described by the cubic
      complex Ginzburg-Landau equation. For stronger non-Boussinesq effects the Hopf
      bifurcation becomes subcritical and the oscillations exhibit localized chaotic
      bursting, which is modeled by a quintic complex Ginzburg-Landau equation.

PMID- 16606098
TI  - Structural properties of screened Coulomb balls.
AB  - Small three-dimensional strongly coupled charged particles in a spherical
      confinement potential arrange themselves in a nested shell structure. By means of
      experiments, computer simulations, and theoretical analysis, the sensitivity of
      their structural properties to the type of interparticle forces is explored.
      While the normalized shell radii are found to be independent of shielding, the
      shell occupation numbers are sensitive to screening and are quantitatively
      explained by an isotropic Yukawa model.

PMID- 16606099
TI  - Anisotropic turbulent spectra in the terrestrial magnetosheath as seen by the
      cluster spacecraft.
AB  - Here we report the first three-dimensional spatial spectrum of the low frequency
      magnetic turbulence obtained from the four Cluster spacecraft in the terrestrial
      magnetosheath close to the magnetopause. We show that the turbulence is
      compressible and dominated by mirror structures, its energy is injected at a
      large scale kp approximately 0.3 (l approximately 2000 km) via a mirror
      instability well predicted by linear theory, and cascades nonlinearly and
      unexpectedly up to kp approximately 3.5 (l approximately 150 km), revealing a new
      power law in the inertial range not predicted by any turbulence theory, and its
      strong anisotropy is controlled by the static magnetic field and the magnetopause
      normal.

PMID- 16606100
TI  - Ion viscous heating in a magnetohydrodynamically unstable Z pinch at over 2 x
      10(9) Kelvin.
AB  - Pulsed power driven metallic wire-array Z pinches are the most powerful and
      efficient laboratory x-ray sources. Furthermore, under certain conditions the
      soft x-ray energy radiated in a 5 ns pulse at stagnation can exceed the estimated
      kinetic energy of the radial implosion phase by a factor of 3 to 4. A theoretical
      model is developed here to explain this, allowing the rapid conversion of
      magnetic energy to a very high ion temperature plasma through the generation of
      fine scale, fast-growing m = 0 interchange MHD instabilities at stagnation. These
      saturate nonlinearly and provide associated ion viscous heating. Next the ion
      energy is transferred by equipartition to the electrons and thus to soft x-ray
      radiation. Recent time-resolved iron spectra at Sandia confirm an ion temperature
      Ti of over 200 keV (2 x 10(9) degrees), as predicted by theory. These are
      believed to be record temperatures for a magnetically confined plasma.

PMID- 16606101
TI  - Screening and attraction of dust particles in plasmas.
AB  - The potential around a dust particle in a plasma is found using the collisional
      hydrodynamic equations of dusty plasmas, taking into account ion-dust and ion
      neutral collisions and considering the plasma source proportional to the dust
      density. The linear screening is strongly influenced by the collisions and can
      substantially differ from Debye screening. Attraction of negatively charged dust
      particles can occur due to overscreening by the ion fluxes in the presence of
      friction forces.

PMID- 16606102
TI  - Coherent control of THz wave generation in ambient air.
AB  - Our study of THz wave generation in the pulsed laser induced air plasma with
      individually controlled phase, polarization, and amplitude of the optical
      fundamental wave (omega) and its second harmonic (2omega) indicates that the
      third-order nonlinear optical process mixing the omega and 2omega beams in the
      ionized plasma is the main mechanism of the efficient THz wave generation. The
      polarity and the strength of the emitted THz field are completely controlled by
      the relative phase between the omega and 2omega waves. The measured THz field
      amplitude is proportional to the pulse energy of the fundamental beam and to the
      square root of the pulse energy of the second-harmonic beam once the total
      optical pulse energy exceeds the plasma formation threshold. The optimal THz
      field is achieved when all waves (omega, 2omega, and THz waves) are at the same
      polarization in the four-wave-mixing process.

PMID- 16606103
TI  - Orientational defects in ice Ih: an interpretation of electrical conductivity
      measurements.
AB  - We present a first-principles study of the structure and energetics of Bjerrum
      defects in ice Ih and compare the results to experimental electrical conductivity
      data. While the DFT result for the activation energy is in good agreement with
      experiment, we find that its two components have quite different values. Aside
      from providing new insight into the fundamental parameters of the microscopic
      electrical theory of ice, our results suggest the activity of traps in doped ice
      in the temperature regime typically assumed to be controlled by the free
      migration of L defects.

PMID- 16606104
TI  - Adiabatic shear failure and dynamic stored energy of cold work.
AB  - Dynamic testing of statically predeformed specimens of magnesium (AM50) shows
      that the failure strain increases with the level of prestrain. Interrupted and
      other dynamic tests show that the temperature rise prior to localization has only
      a minor influence on adiabatic shear band (ASB) formation. For all the tests, the
      dynamic deformation energy until ASB formation is found to be relatively
      constant, indicating that ASB is dependent almost solely on dynamic deformation
      processes, with quasistatic and thermal effects prior to localization being very
      marginal. We suggest the concept of a constant dynamic mechanical energy
      (toughness) as a quantitative criterion for ASB formation--this concept being
      related physically to the dynamic stored energy of cold work. All in all, the
      tests indicate that ASB failure is more dependent on energy considerations that
      on strain criteria, as has been considered until now.

PMID- 16606105
TI  - Strain rate induced crystallization in bulk metallic glass-forming liquid.
AB  - We report on the solidification of Au49, Ag5.5, Pd2.3, Cu26.9, Si16.3 bulk
      metallic glass under various strain rates. Using a copper mold casting technique
      with a low strain rate during solidification, this alloy is capable of forming
      glassy rods of at least 5 mm in diameter. Surprisingly, when the liquid alloy is
      splat cooled at much higher cooling rates and large strain rates, the solidified
      alloy is no longer fully amorphous. Our finding suggests that the large strain
      rate during splat cooling induces crystallization. The pronounced difference in
      crystallization behavior cannot be explained by the previously observed strain
      rate effect on viscosity alone. A strain rate induced phase separation process is
      suggested as one of the explanations for this crystallization behavior. The
      strain-rate-dependent critical cooling rate must be considered in order to assess
      the intrinsic glass forming ability of metallic liquid.

PMID- 16606106
TI  - In Situ HREM observation of crystalline-to-gas transition in nanometer-sized Ag
      particles.
AB  - Sublimation of silver atoms from a nanometer-sized silver particle, namely, the
      crystalline-to-gas transition, has been directly observed by high resolution
      electron microscopy. Remarkable sublimation of silver atoms took place at 950 K
      from an approximately 9-nm-sized crystalline silver particle on the graphite
      substrate. The sublimation continued until the whole silver particle disappeared.
      No melting of the particle occurred during this process. The height-to-width
      ratio of a nanometer-sized silver particle on graphite at 950 K was about 0.65,
      and the ratio did not change so much during the sublimation-induced shrinkage of
      the particle.

PMID- 16606107
TI  - Size dependence of Young's modulus in ZnO nanowires.
AB  - We report a size dependence of Young's modulus in [0001] oriented ZnO nanowires
      (NWs) with diameters ranging from 17 to 550 nm for the first time. The measured
      modulus for NWs with diameters smaller than about 120 nm is increasing
      dramatically with the decreasing diameters, and is significantly higher than that
      of the larger ones whose modulus tends to that of bulk ZnO. A core-shell
      composite NW model in terms of the surface stiffening effect correlated with
      significant bond length contractions occurred near the {1010} free surfaces
      (which extend several layers deep into the bulk and fade off slowly) is proposed
      to explore the origin of the size dependence, and present experimental result is
      well explained. Furthermore, it is possible to estimate the size-related elastic
      properties of GaN nanotubes and relative nanostructures by using this model.

PMID- 16606108
TI  - Carbon ad-dimer defects in carbon nanotubes.
AB  - The adsorption of carbon dimers on carbon nanotubes leads to a rich spectrum of
      structures and electronic structure modifications. Barriers for the formation of
      carbon dimer induced defects are calculated and found to be considerably lower
      than those for the Stone-Wales defect. The electronic states introduced by the ad
      dimers depend on defect structure and tube type and size. Multiple carbon ad
      dimers provide a route to structural engineering of patterned tubes that may be
      of interest for nanoelectronics.

PMID- 16606109
TI  - Shape of a wave front in a heterogenous medium.
AB  - Wave propagation in a heterogeneous medium, characterized by a distribution of
      local elastic moduli, is studied. Both acoustic and elastic waves are considered,
      as are spatially random and power-law correlated distributions of the elastic
      moduli with nondecaying correlations. Three models--a continuum scalar model, and
      two discrete models--are utilized. Numerical simulations indicate the existence,
      at all times, of the relation, alpha = H, where alpha is the roughness exponent
      of the wave front in the medium, and H is the Hurst exponent that characterizes
      the spatial correlations in the distribution of the local elastic moduli. Hence,
      a direct relation between the static morphology of an inhomogeneous correlated
      medium and its dynamical properties is established. In contrast, for a wave front
      in random media, alpha = 0 (logarithmic growth) at short times, followed by a
      crossover to the classical value, alpha = 1/2, at long times.

PMID- 16606110
TI  - Thermodynamic equilibrium of water and ice at room temperature under an electric
      field in unbounded media.
AB  - Based on thermodynamical considerations, we show that water and ice in an
      unbounded medium can coexist as different phases at room temperature under the
      effect of the variable (frequency of about 10(5) Hz) electric field of about 4 x
      10(5) V/cm. The latter value is much weaker than that theoretically predicted for
      alignment of water dipoles (>10(7) V/cm), but somewhat greater than the
      experimental data (2-8) x 10(4) V/cm, which have been obtained recently for
      freezing of water confined between solid walls separated by only a few molecular
      diameters.

PMID- 16606111
TI  - Pattern formation and glassy phase in the phi4 theory with a screened
      electrostatic repulsion.
AB  - We study analytically the structural properties of a system with a short-range
      attraction and a competing long-range screened repulsion. This model contains the
      essential features of the effective interaction potential among charged colloids
      in polymeric solutions and provides novel insights on the equilibrium phase
      diagram of these systems. Within the self-consistent Hartree approximation and by
      using a replica approach, we show that varying the parameters of the repulsive
      potential and the temperature yields a phase coexistence, a lamellar, and a
      glassy phase. Our results strongly suggest that the cluster phase observed in
      charged colloids might be the signature of an underlying equilibrium lamellar
      phase, hidden on experimental time scales.

PMID- 16606112
TI  - Spontaneous 2D accumulation of charged Be dopants in GaAs p-n superlattices.
AB  - In a classical view, abrupt dopant profiles in semiconductors tend to be smoothed
      out by diffusion due to concentration gradients and repulsive screened Coulomb
      interactions between the charged dopants. We demonstrate, however, using cross
      sectional scanning tunneling microscopy and secondary ion mass spectroscopy, that
      charged Be dopant atoms in GaAs p-n superlattices spontaneously accumulate and
      form two-dimensional dopant layers. These are stabilized by reduced repulsive
      screened Coulomb interactions between the charged dopants arising from the two
      dimensional quantum mechanical confinement of charge carriers.

PMID- 16606113
TI  - Long range substrate mediated mass transport on metal surfaces induced by adatom
      clusters.
AB  - Mass transport at surfaces can proceed either (i) by hopping diffusion of atoms
      on top of the surface from one site to another or (ii) by propagation of small
      displacements from one atom to the next within the topmost atomic layer. In the
      latter case, a long range substrate mediated mass transport has been postulated
      but never observed explicitly. Experimental and theoretical evidence is shown
      here for the occurrence of such a mechanism on the reconstructed Au(111) surface,
      where the movement is shown to be well described by a soliton.

PMID- 16606114
TI  - Pinning frequencies of the collective modes in alpha-uranium.
AB  - Uranium is the only known element that features a charge-density wave (CDW) and
      superconductivity. We report a comparison of the specific heat of single-crystal
      and polycrystalline alpha-uranium. In the single crystal we find excess
      contributions to the heat capacity at 41 K, 38 K, and 23 K, with a Debye
      temperature ThetaD = 265 K. In the polycrystalline sample the heat capacity curve
      is thermally broadened (ThetaD = 184 K), but no excess heat capacity was
      observed. The excess heat capacity Cphi (taken as the difference between the
      single-crystal and polycrystal heat capacities) is well described in terms of
      collective-mode excitations above their respective pinning frequencies. This
      attribution is represented by a modified Debye spectrum with two cutoff
      frequencies, a pinning frequency V0 for the pinned CDW (due to grain boundaries
      in the polycrystal), and a normal Debye acoustic frequency occurring in the
      single crystal.

PMID- 16606115
TI  - Bulk- and surface-sensitive high-resolution photoemission study of two mott
      hubbard systems: SrVO3 and CaVO3.
AB  - We study the electronic structure of Mott-Hubbard systems SrVO3 and CaVO3 with
      bulk and surface-sensitive high-resolution photoemission spectroscopy, using a
      vacuum ultraviolet laser, synchrotron radiation, and a discharge lamp (hv = 7-21
      eV). A systematic suppression of the density of states (DOS) within approximately
      0.2 eV of the Fermi level (EF) is found on decreasing photon energy, i.e., on
      increasing bulk sensitivity. The coherent band in SrVO3 and CaVO3 is shown to
      consist of surface and bulk-derived features, separated in energy. The stronger
      distortion on surface of CaVO3 compared to SrVO3 leads to a higher surface
      metallicity in the coherent DOS at EF, consistent with recent theory.

PMID- 16606116
TI  - Electron transport in a multichannel one-dimensional conductor: molybdenum
      selenide nanowires.
AB  - We have measured electron transport in small bundles of identical conducting
      molybdenum selenide nanowires where the number of weakly interacting one
      dimensional chains ranges from 1 to 300. The linear conductance and current in
      these nanowires exhibit a power-law dependence on temperature and bias voltage,
      respectively. The exponents governing these power laws decrease as the number of
      conducting channels increase. These exponents can be related to the electron
      electron interaction parameter for transport in multichannel 1D systems with a
      few defects.

PMID- 16606117
TI  - Electron conductive three-dimensional polymer of cuboidal C60.
AB  - Single crystals of three-dimensional (3D) C60 polymer were prepared by the
      topotactic conversion of two-dimensional (2D) C60 polymer single crystals at a
      pressure of 15 GPa at 600 degrees C. The x-ray single crystal study revealed that
      the 3D C60 polymer crystallized in a body centered orthorhombic space group Immm,
      and spherical C60 monomer units were substantially deformed to rectangular
      parallelepiped (cuboidal) shapes, each unit being bonded to eight cuboidal C60
      neighbors via [3 + 3] cycloaddition. The 3D C60 polymer was electron conductive,
      in contrast with the nonconductive behavior of 2D polymers.

PMID- 16606118
TI  - Delocalization in weakly coupled disordered wires: application to conjugated
      polymers.
AB  - It is well known that even for minimal disorder one-dimensional wires are
      insulators: all 1D electron states are localized. Here, the influence of
      interwire coupling on delocalization of 1D states is examined. Based on
      perturbation theoretic arguments for the formation of 3D states in coupled wires
      and subsequent scaling analysis, practical expressions for the microscopic
      conditions of electronic delocalization and coherent conductivity of coupled 1D
      wires are obtained. The model quantitatively explains the temperature dependent
      dc conductivity in conducting polymers at both sides of the metal-insulator
      transition and links the experimental data to microscopic material parameters.

PMID- 16606119
TI  - Proper definition of spin current in spin-orbit coupled systems.
AB  - The conventional definition of spin current is incomplete and unphysical in
      describing spin transport in systems with spin-orbit coupling. A proper and
      measurable spin current is established in this study, which fits well into the
      standard framework of near-equilibrium transport theory and has the desirable
      property to vanish in insulators with localized orbitals. Experimental
      implications of our theory are discussed.

PMID- 16606120
TI  - Counting statistics of single electron transport in a quantum dot.
AB  - We have measured the full counting statistics of current fluctuations in a
      semiconductor quantum dot (QD) by real-time detection of single electron
      tunneling with a quantum point contact. This method gives direct access to the
      distribution function of current fluctuations. Suppression of the second moment
      (related to the shot noise) and the third moment (related to the asymmetry of the
      distribution) in a tunable semiconductor QD is demonstrated experimentally. With
      this method we demonstrate the ability to measure very low current and noise
      levels.

PMID- 16606121
TI  - Competing periodicities in fractionally filled one-dimensional bands.
AB  - We present a variable temperature scanning tunneling microscopy and spectroscopy
      study of the Si(553)-Au atomic chain reconstruction. This quasi-one-dimensional
      system undergoes at least two charge density wave (CDW) transitions, which can be
      attributed to electronic instabilities in the fractionally filled 1D bands of the
      high-symmetry phase. Upon cooling, Si(553)-Au first undergoes a single-band
      Peierls distortion, resulting in period doubling along the chains. This Peierls
      state is ultimately overcome by a competing x3 CDW, which is accompanied by a x2
      periodicity in between the chains. These locked-in periodicities indicate small
      charge transfer between the nearly 1/2-filled and 1/4-filled bands. The presence
      and the mobility of atomic-scale dislocations in the x3 CDW state indicates the
      possibility of manipulating phase solitons carrying a (spin, charge) of (1/2, +/-
      e/3) or (0, +/-2e/3).

PMID- 16606122
TI  - Contact dependence of carrier injection in carbon nanotubes: an ab initio study.
AB  - We combine ab initio density functional theory with transport calculations to
      provide a microscopic basis for distinguishing between good and poor metal
      contacts to nanotubes. Comparing Ti and Pd as examples of different contact
      metals, we trace back the observed superiority of Pd to the nature of the metal
      nanotube hybridization. Based on large scale Landauer transport calculations, we
      suggest that the optimum metal-nanotube contact combines a weak hybridization
      with a large contact length between the metal and the nanotube.

PMID- 16606123
TI  - Conductance oscillations in squashed carbon nanotubes.
AB  - We report measurements on the radial electromechanical properties of single
      walled carbon nanotubes. By measuring the conductance of the nanotube, we show
      that a gap is opened while squashing the nanotubes and that during the
      deformation stages we observe at least two open-close cycles of the gap. We
      employ a novel experimental setup where an atomic force microscope tip is used
      both as an electrode and to induce radial deformations. In contrast with prior
      experiments reported, this technique allows direct probing of the local
      electronic structure of carbon nanotubes as they are radially deformed.

PMID- 16606124
TI  - Direct observation of the Aharonov-Casher phase.
AB  - Ring structures fabricated from HgTe/HgCdTe quantum wells have been used to study
      Aharonov-Bohm type conductance oscillations as a function of Rashba spin-orbit
      splitting strength. We observe nonmonotonic phase changes indicating that an
      additional phase factor modifies the electron wave function. We associate these
      observations with the Aharonov-Casher effect. This is confirmed by comparison
      with numerical calculations of the magnetoconductance for a multichannel ring
      structure within the Landauer-Buttiker formalism.

PMID- 16606125
TI  - Intervalley gap anomaly of two-dimensional electrons in silicon.
AB  - We report here a systematic study of the energy gaps at the odd-integer quantum
      Hall states nu = 3 and 5 under tilted magnetic (B) fields in a high quality Si
      two-dimensional electron system. Out of the coincidence region, the valley
      splitting is independent of the in-plane fields. However, the nu = 3 valley gap
      differs by about a factor of 3 (Deltav approximately 0.4 vs 1.2 K) on different
      sides of the coincidence. More surprisingly, instead of reducing to zero, the
      energy gaps at nu = 3 and 5 rise rapidly when approaching the coincidence angles.
      We believe that such an anomaly is related to strong couplings of the nearly
      degenerate Landau levels.

PMID- 16606127
TI  - Spin-wave contribution to the nuclear spin-lattice relaxation in triplet
      superconductors.
AB  - We discuss collective spin-wave excitations in triplet superconductors with an
      easy axis anisotropy for the order parameter. Using a microscopic model for
      interacting electrons, we estimate the frequency of such excitations in Bechgaard
      salts and ruthenate superconductors to be 1 and 20 GHz, respectively. We
      introduce an effective bosonic model to describe spin-wave excitations and
      calculate their contribution to the nuclear spin-lattice relaxation rate. We find
      that, in the experimentally relevant regime of temperatures, this mechanism leads
      to the power law scaling of 1/T1 with temperature. For two- and three-dimensional
      systems, the scaling exponents are 3 and 5, respectively. We discuss experimental
      manifestations of the spin-wave mechanism of the nuclear spin-lattice relaxation.

PMID- 16606126
TI  - Enhancement of the critical current density of YBa2Cu3Ox superconductors under
      hydrostatic pressure.
AB  - The dependence of the critical current density Jc on hydrostatic pressure to 0.6
      GPa is determined for a single 25 degrees [001]-tilt grain boundary in a
      bicrystalline ring of nearly optimally doped melt-textured YBa2Cu3Ox. Jc is found
      to increase rapidly under pressure at +20%/GPa. A new diagnostic method is
      introduced (pressure-induced Jc relaxation) which reveals a sizable concentration
      of vacant oxygen sites in the grain boundary region. Completely filling such
      sites with oxygen anions should lead to significant enhancements in Jc.

PMID- 16606128
TI  - Observation of the crossover from two-gap to single-gap superconductivity through
      specific heat measurements in neutron-irradiated MgB2.
AB  - We report specific heat measurements on neutron-irradiated MgB2 samples, for
      which the critical temperature is lowered to 8.7 K, but the superconducting
      transition remains extremely sharp, indicative of a defect structure extremely
      homogeneous. Our results evidence the presence of two superconducting gaps in the
      temperature range above 21 K, while single-gap superconductivity is well
      established as a bulk property, not associated with local disorder fluctuations,
      when Tc decreases to 11 K.

PMID- 16606129
TI  - Lightly doped La2-xSrxCuO4 as a Lifshitz helimagnet.
AB  - We study the static magnetic correlations in lightly doped La2-xSrxCuO4 within
      the framework of a dipolar frustration model for a canted antiferromagnet. We
      show that the stability of the canted Neel state for x < 2% is due to the
      Dzyaloshinskii-Moriya and XY anisotropies. For higher doping, the ground state is
      unstable towards a helicoidal magnetic phase, where the transverse components of
      the staggered magnetization rotate in a plane perpendicular to the orthorhombic b
      axis. Our theory reconciles, for the first time, the incommensurate peaks
      observed in elastic neutron scattering with Raman and magnetic susceptibility
      experiments in La2-xSrxCuO4 .

PMID- 16606130
TI  - Direct observation of vortex shells and magic numbers in mesoscopic
      superconducting disks.
AB  - We have studied vortex configurations in mesoscopic superconducting disks using
      the Bitter decoration technique. For a broad range of vorticities L the circular
      geometry is found to lead to the formation of concentric shells of vortices. From
      images obtained on disks of different sizes in a range of magnetic fields we
      traced the evolution of vortex states and identified stable and metastable
      configurations of interacting vortices. Furthermore, the analysis of shell
      filling with increasing L allowed us to identify magic numbers corresponding to
      the appearance of consecutive new shells.

PMID- 16606131
TI  - Polarized resonant inelastic x-ray scattering as an ultrafine probe of excited
      States of La2CuO4.
AB  - X-ray absorption is the standard method to probe the unoccupied density of states
      at a given edge. Here we show that polarized resonant inelastic x-ray scattering
      in La2CuO4 at the Cu L edge is extremely sensitive to the environment of the Cu
      atom and the fine structure in the Cu 4p density of states. Combined ab initio
      and many-body cluster calculations, used for the first time in such a context,
      show remarkable agreement with experiment. In particular, we identify a nonlocal
      effect, namely, a transition to off-site Cu 3d states.

PMID- 16606133
TI  - Magnetization reversal in a novel gradient nanomaterial.
AB  - The deposition of Co/Pd multilayer films onto self-assembled particle arrays with
      particle sizes down to 50 nm leads to pronounced curvature-induced physical
      properties. Unlike in classical nanosystems, the so-formed single caps on top of
      the spherical particles exhibit a radial symmetric anisotropy orientation across
      their surface. Its impact on the magnetization reversal process was analyzed
      experimentally for different particle sizes and compared to micromagnetic
      simulations, offering new opportunities in the functionalization of magnetic
      nanostructures.

PMID- 16606132
TI  - Unified description of bulk and interface-enhanced spin pumping.
AB  - We describe a mechanism for generating nonequilibrium electron-spin accumulation
      in semiconductors or metals by rf magnetic field pumping. With a semiclassical
      model we show that a rotating applied magnetic field (or the processing
      magnetization inside a weak ferromagnet) generates a dc spin accumulation. For
      bulk systems this spin accumulation is in general given by a small fraction of h
      omega, where omega is the rotation or precession frequency. With the addition of
      a neighboring, field-free region, and allowing for the diffusion of spins across
      the interface, the spin accumulation is dramatically enhanced towards h omega
      near the interface. The interface-enhanced spin accumulation obtained within our
      bulk-oriented model is surprisingly similar to predictions based on interface
      scattering theory [A. Brataas, Phys. Rev. B 66, 060404(R) (2002)].

PMID- 16606134
TI  - Anomalous Hall effect in La0.7Sr0.3MnO3/SrTiO3 superlattices: hopping transport
      and a probe of dimensionality.
AB  - The anomalous Hall effect (AHE) in La0.7Sr0.3MnO3/SrTiO3 (LSMO/STO) superlattices
      was analyzed using theories of the Berry phase effect. The temperature-dependent
      anomalous Hall coefficient Rs is found to be expressed by -Rs = Rs0
      exp[(T/T0)1.5], where Rs0 is a prefactor and T0 is in units of kelvin, and is
      explained by the carrier-hopping mechanism. In addition, a scaling analysis for
      the Hall resistivity as a function of magnetization supports the scenario of the
      Berry phase effects. Furthermore, a shifting extremum of Hall resistivity in
      LSMO/STO superlattices is observed and regarded as a probe of dimensionality in
      quasi-two-dimensional systems.

PMID- 16606135
TI  - Bose-Einstein condensation of S = 1 nickel spin degrees of freedom in NiCl2
      4SC(NH2)2.
AB  - It has recently been suggested that the organic compound NiCl2-4SC(NH2)2 (DTN)
      undergoes field-induced Bose-Einstein condensation (BEC) of the Ni spin degrees
      of freedom. The Ni S = 1 spins exhibit three-dimensional XY antiferromagnetism
      above a critical field H(c1) approximately 2 T. The spin fluid can be described
      as a gas of hard-core bosons where the field-induced antiferromagnetic transition
      corresponds to Bose-Einstein condensation. We have determined the spin
      Hamiltonian of DTN using inelastic neutron diffraction measurements, and we have
      studied the high-field phase diagram by means of specific heat and magnetocaloric
      effect measurements. Our results show that the field-temperature phase boundary
      approaches a power-law H - H(c1) proportional variant T(alpha)(c) near the
      quantum critical point, with an exponent that is consistent with the 3D BEC
      universal value of alpha = 1.5.

PMID- 16606136
TI  - Phase separation in the itinerant metamagnetic transition of Sr4Ru3O10.
AB  - We have investigated the electronic transport properties of the triple-layered
      ruthenate Sr4Ru3O10. We observed surprising anomalous features near its itinerant
      metamagnetic transition, including ultrasharp magnetoresistivity steps, a
      nonmetallic temperature dependence in resistivity for upward field sweeps, and a
      resistivity drop in temperature dependence for downward field sweeps. These
      features suggest that the metamagnetic transition of Sr4Ru3O10 occurs via an
      electronic phase separation process with magnetic domain formation.

PMID- 16606137
TI  - Scaling of geometric phases close to the quantum phase transition in the XY spin
      chain.
AB  - We show that the geometric phase of the ground state in the XY model obeys
      scaling behavior in the vicinity of a quantum phase transition. In particular we
      find that the geometric phase is nonanalytical and its derivative with respect to
      the field strength diverges at the critical magnetic field. Furthermore, the
      universality in the critical properties of the geometric phase in a family of
      models is verified. In addition, since the quantum phase transition occurs at a
      level crossing or avoided level crossing and these level structures can be
      captured by the Berry curvature, the established relation between the geometric
      phase and quantum phase transitions is not a specific property of the XY model,
      but a very general result of many-body systems.

PMID- 16606138
TI  - Evidence for a new magnetic field scale in CeCoIn5.
AB  - The Nernst coefficient of displays two distinct anomalies in magnetic field. The
      feature detected at Hk approximately 23 T is similar to what is observed in
      CeRu2Si2 at Hm = 7.8 T where a metamagnetic transition occurs. In CeCoIn5, new
      frequencies are observed in de Haas-van Alphen oscillations when the field
      exceeds 23 T where the Dingle temperature decreases by about 30%. Based on the
      Nernst coefficient anomalies, the magnetic phase diagram of CeCoIn5 is revised.

PMID- 16606139
TI  - Field emission tip as a nanometer source of free electron femtosecond pulses.
AB  - We report a source of free electron pulses based on a field emission tip
      irradiated by a low-power femtosecond laser. The electron pulses are shorter than
      70 fs and originate from a tip with an emission area diameter down to 2 nm.
      Depending on the operating regime we observe either photofield emission or
      optical field emission with up to 200 electrons per pulse at a repetition rate of
      1 GHz. This pulsed electron emitter, triggered by a femtosecond oscillator, could
      serve as an efficient source for time-resolved electron interferometry, for time
      resolved nanometric imaging and for synchrotrons.

PMID- 16606140
TI  - Optical sum-frequency emission from langmuir-blodgett films of variable
      thickness: effects of the substrate and polar orientation of fatty acids in the
      films.
AB  - The nonlinear optical response arising from a model multilayer structure, i.e.,
      Langmuir-Blodgett (LB) films comprised of different numbers of per-protonated (H)
      and per-deuterated (D) fatty acid layers on solid substrates, has been evaluated
      by sum-frequency generation (SFG) spectroscopy. The SFG signals depend
      significantly on the absolute polar orientation of the fatty acids in the
      individual layers and on the nonlinear optical response of the substrate. The SFG
      spectra on gold and fused quartz substrates demonstrate a totally different
      dependence on the number of the contributing H layers, which it is possible to
      analyze quantitatively. The results provide important information for
      understanding the origin of the nonlinear optical responses from ordered systems
      composed of multiple interfaces and therefore for extracting exact structural
      information about each interface from the observed SFG signals.

PMID- 16606141
TI  - Optical modes in semiconductor microtube ring resonators.
AB  - We demonstrate optical modes in InGaAs/GaAs microtubes acting as optical ring
      resonators. Self-supporting microtubes were fabricated by optical lithography and
      wet-etching processes utilizing the self-rolling mechanism of strained bilayers.
      The optical modes were probed by the photoluminescence of InAs quantum dots
      embedded in the tube's wall. In this novel microtube ring resonator we find a
      spectrum of sharp modes. They are in very good agreement with the theoretical
      results for a closed thin dielectric waveguide.

PMID- 16606142
TI  - The frozen state in the liquid phase of side-chain liquid-crystal polymers.
AB  - Quenched isotropic melts of side-chain liquid-crystal polymers reveal
      surprisingly an anisotropic polymer conformation. This small-angle neutron
      scattering (SANS) result is consistent with the identification of a macroscopic,
      solidlike response in the isotropic phase. Both experiments (rheology and SANS)
      indicate that the polymer system appears frozen on millimeter length scales and
      at the time scales of the observation. This result implies that the flow behavior
      is not the terminal behavior and that cross-links or entanglements are not a
      necessary condition to provide elasticity in melts.

PMID- 16606143
TI  - Glassy conformations in wrinkled membranes.
AB  - Partially polymerized membranes display a striking mechanical transition at low
      temperature known as the wrinkling transition. Fluorescence and scanning electron
      microscopy as well as profile measurements using an atomic force microscope
      revealed the existence of three degrees of wrinkling depending on the degree of
      the membrane polymerization. At low polymerization the membrane undergoes a
      cascade of wrinkling to form a folded phase with a characteristic exponent eta
      equal to 3, at intermediate polymerization, the membrane is in an intermediate
      wrinkled phase (similar to the crumpling of an elastic sheet) with eta
      approximately 2.5, while at high polymerization the membrane undergoes an abrupt
      "compaction" to the wrinkled-rough phase with eta approximately 2.

PMID- 16606144
TI  - Continuum theory of retroviral capsids.
AB  - We present a self-assembly phase diagram for the shape of retroviral capsids,
      based on continuum elasticity theory. The spontaneous curvature of the capsid
      proteins drives a weakly first-order transition from spherical to
      spherocylindrical shapes. The conical capsid shape which characterizes the HIV-1
      retrovirus is never stable under unconstrained energy minimization. Only under
      conditions of fixed volume and/or fixed spanning length can the conical shape be
      a minimum energy structure. Our results indicate that, unlike the capsids of
      small viruses, retrovirus capsids are not uniquely determined by the molecular
      structure of the constituent proteins but depend in an essential way on physical
      constraints present during assembly.

PMID- 16606146
TI  - Functional modes of proteins are among the most robust.
AB  - It is shown that a small subset of modes which are likely to be involved in
      protein functional motions of large amplitude can be determined by retaining the
      most robust normal modes obtained using different protein models. This result
      should prove helpful in the context of several applications proposed recently,
      like for solving difficult molecular replacement problems or for fitting atomic
      structures into low-resolution electron density maps. It may also pave the way
      for the development of methods allowing us to predict such motions accurately.

PMID- 16606145
TI  - Effective potentials for folding proteins.
AB  - A coarse-grained off-lattice model that is not biased in any way to the native
      state is proposed to fold proteins. To predict the native structure in a
      reasonable time, the model has included the essential effects of water in an
      effective potential. Two new ingredients, the dipole-dipole interaction and the
      local hydrophobic interaction, are introduced and are shown to be as crucial as
      the hydrogen bonding. The model allows successful folding of the wild-type
      sequence of protein G and may have provided important hints to the study of
      protein folding.

PMID- 16606147
TI  - Mean chain length of adsorbed supramolecular polymers.
AB  - We present a theoretical study of reversible supramolecular polymers near an
      adsorbing surface. Mean chain lengths for free and adsorbed supramolecular
      polymers were calculated for a broad range of concentrations. As far as we know,
      this is the first report that describes a regime where the mean chain length
      decreases with increasing monomer concentration. It is shown that this anomalous
      behavior is caused by a change of the structure of the adsorbed layer.

PMID- 16606148
TI  - Surface wave assisted self-assembly of multidomain magnetic structures.
AB  - An ensemble of magnetic microparticles at the liquid surface displays novel
      snakelike self-assembled structures induced by an alternating magnetic field. We
      demonstrate that these structures are directly related to surface waves in the
      liquid generated by the collective response of magnetic microparticles to the
      alternating magnetic field. The segments of the "snake" exhibit long-range
      antiferromagnetic ordering, while each segment is composed of ferromagnetically
      aligned chains of microparticles. The structures exhibit magnetic hysteretic
      behavior with respect to an external in-plane magnetic field and logarithmic
      relaxation of the remanent magnetic moment.

PMID- 16606149
TI  - Comment on "Quantum key distribution with blind polarization bases".

PMID- 16606151
TI  - Comment on "Magnetism in atomic-size palladium contacts and nanowires".

PMID- 16606153
TI  - Comment on "Dissociation of O2 at Al(111): the role of spin selection rules".

PMID- 16606155
TI  - Effective theory of excitations in a Feshbach-resonant superfluid.
AB  - A strongly interacting Fermi gas, such as that of cold atoms operative near a
      Feshbach resonance, is difficult to study by perturbative many-body theory to go
      beyond mean-field approximation. Here I develop an effective field theory for the
      resonant superfluid based on broken symmetry. The theory retains both fermionic
      quasiparticles and superfluid phonons, the interaction between them being derived
      nonperturbatively. The theory converges and can be improved order by order, in a
      manner governed by a low energy expansion rather than by a coupling constant. I
      apply the effective theory to calculate the specific heat and discuss the theory
      with a recent heat capacity experiment.

PMID- 16606156
TI  - Direct experimental evidence of free-fermion antibunching.
AB  - Fermion antibunching was observed on a beam of free noninteracting neutrons. A
      monochromatic beam of thermal neutrons was first split by a graphite single
      crystal, then fed to two detectors, displaying a reduced coincidence rate. The
      result is a fermionic complement to the Hanbury Brown and Twiss effect for
      photons.

PMID- 16606157
TI  - Casimir Interaction between a plate and a cylinder.
AB  - We find the exact Casimir force between a plate and a cylinder, a geometry
      intermediate between parallel plates, where the force is known exactly, and the
      plate sphere, where it is known at large separations. The force has an
      unexpectedly weak decay approximately L/[H3 ln(H/R)] at large plate-cylinder
      separations H (L and R are the cylinder length and radius), due to transverse
      magnetic modes. Path integral quantization with a partial wave expansion
      additionally gives a qualitative difference for the density of states of electric
      and magnetic modes, and corrections at finite temperatures.

PMID- 16606158
TI  - Bosonization, pairing, and superconductivity of the fermionic Tonks-Girardeau
      gas.
AB  - We determine some exact static and time-dependent properties of the fermionic
      Tonks-Girardeau (FTG) gas, a spin-aligned one-dimensional Fermi gas with
      infinitely strongly attractive zero-range odd-wave interactions. We show that its
      two-particle reduced density matrix exhibits superconductive off-diagonal long
      range order, and on a ring an FTG gas with an even number of atoms has a highly
      degenerate ground state with quantization of Coriolis rotational flux and high
      sensitivity to rotation and to external fields and accelerations. For a gas
      initially under harmonic confinement, we show that during an expansion the
      momentum distribution undergoes a "dynamical bosonization," approaching that of
      an ideal Bose gas without violating the Pauli exclusion principle.

PMID- 16606159
TI  - Einstein-de Haas effect in dipolar Bose-Einstein condensates.
AB  - The general properties of the order parameter for a dipolar spinor Bose-Einstein
      condensate are discussed based on symmetries of interactions. An initially spin
      polarized dipolar condensate is shown to dynamically generate a nonsingular
      vortex via spin-orbit interactions--a phenomenon reminiscent of the Einstein-de
      Haas effect in ferromagnets.

PMID- 16606160
TI  - Entanglement reciprocation between qubits and continuous variables.
AB  - We investigate how entanglement can be transferred between qubits and continuous
      variable (CV) systems. We find that one ebit borne in maximally entangled qubits
      can be fully transferred to two CV systems which are initially prepared in a pure
      separable Gaussian field with high excitation. We show that it is possible to
      retrieve the entanglement back to qubits from the entangled CV systems. The
      deposition of multiple ebits from qubits to the initially separable CV systems is
      also pointed out. We show that the entanglement transfer and retrieval are done
      at a quasisteady state.

PMID- 16606161
TI  - Extremality of Gaussian quantum states.
AB  - We investigate Gaussian quantum states in view of their exceptional role within
      the space of all continuous variables states. A general method for deriving
      extremality results is provided and applied to entanglement measures, secret key
      distillation and the classical capacity of bosonic quantum channels. We prove
      that for every given covariance matrix the distillable secret key rate and the
      entanglement, if measured appropriately, are minimized by Gaussian states. This
      result leads to a clearer picture of the validity of frequently made Gaussian
      approximations. Moreover, it implies that Gaussian encodings are optimal for the
      transmission of classical information through bosonic channels, if the capacity
      is additive.

PMID- 16606162
TI  - D = 5 Einstein-Maxwell-Chern-Simons black holes.
AB  - Five-dimensional Einstein-Maxwell-Chern-Simons theory with a Chern-Simons
      coefficient lambda = 1 has supersymmetric black holes with a vanishing horizon
      angular velocity but finite angular momentum. Here supersymmetry is associated
      with a borderline between stability and instability, since for lambda > 1 a
      rotational instability arises, where counterrotating black holes appear, whose
      horizon rotates in the opposite sense to the angular momentum. For lambda > 2
      black holes are no longer uniquely characterized by their global charges, and
      rotating black holes with vanishing angular momentum appear.

PMID- 16606163
TI  - Leptogenesis from gravity waves in models of inflation.
AB  - We present a new mechanism for creating the observed cosmic matter-antimatter
      asymmetry which satisfies all three Sakharov conditions from one common thread,
      gravitational waves. We generate lepton number through the gravitational anomaly
      in the lepton number current. The source term comes from elliptically polarized
      gravity waves that are produced during inflation if the inflaton field contains a
      CP-odd component. The amount of matter asymmetry generated in our model can be of
      realistic size for the parameters within the range of some inflationary scenarios
      and grand unified theories.

PMID- 16606164
TI  - Locking information in black holes.
AB  - We show that a central presumption in the debate over black-hole information loss
      is incorrect. Ensuring that information not escape during evaporation does not
      require that it all remain trapped until the final stage of the process. Using
      the recent quantum information-theoretic result of locking, we show that the
      amount of information that must remain can be very small, even as the amount
      already radiated is negligible. Information need not be additive: A small system
      can lock a large amount of information, making it inaccessible. Only if the set
      of initial states is restricted can information leak.

PMID- 16606165
TI  - J-- glueballs and a low odderon intercept.
AB  - We report an odderon Regge trajectory emerging from a field theoretical Coulomb
      gauge QCD model for the odd signature J(PC) (P = C = -1) glueball states. The
      trajectory intercept is clearly smaller than the Pomeron and even the omega
      trajectory's intercept which provides an explanation for the nonobservation of
      the odderon in high energy scattering data. To further support this result we
      compare to glueball lattice data and also perform calculations with an
      alternative model based upon an exact Hamiltonian diagonalization for three
      constituent gluons.

PMID- 16606166
TI  - Topological mass generation in four dimensions.
AB  - We show that in a large class of physically interesting systems the mass
      generation phenomenon can be understood in terms of topological structures,
      without requiring a detailed knowledge of the underlying dynamics. This is first
      demonstrated by showing that Schwinger's mechanism for mass generation relies on
      topological structures of a two-dimensional gauge theory. In the same manner,
      corresponding four-dimensional topological entities give rise to topological mass
      generation in four dimensions. This formulation offers a unified topological
      description of some seemingly unrelated phenomena, such as two-dimensional
      superconductivity, and the generation of eta' and axion masses by QCD, and
      possibly by gravity.

PMID- 16606167
TI  - Neutron-mirror-neutron oscillations: how fast might they be?
AB  - We discuss the phenomenological implications of the neutron (n) oscillation into
      the mirror neutron (n'), a hypothetical particle exactly degenerate in mass with
      the neutron but sterile to normal matter. We show that the present experimental
      data allow a maximal n-n' oscillation in vacuum with a characteristic time tau
      much shorter than the neutron lifetime, in fact as small as 1 sec. This
      phenomenon may manifest in neutron disappearance and regeneration experiments
      perfectly accessible to present experimental capabilities and may also have
      interesting astrophysical consequences, in particular, for the propagation of
      ultra high energy cosmic rays.

PMID- 16606170
TI  - Probing small parton densities in ultraperipheral A A and pA collisions at the
      CERN large Hadron Collider.
AB  - We calculate photoproduction rates for several hard processes in ultraperipheral
      proton-lead and lead-lead collisions at the CERN Large Hadron Collider (LHC) with
      square root of sNN = 8.8 and 5.5 TeV, respectively, which could be triggered in
      the large LHC detectors. We use ATLAS as an example. The lead ion is treated as a
      source of (coherently produced) photons with energies and intensities greater
      than those of equivalent ep collisions at the DESY collider HERA. We find very
      large rates for both inclusive and diffractive production that will extend the
      HERA x range by nearly an order of magnitude for similar virtualities. We
      demonstrate that it is possible to reach the kinematic regime where nonlinear
      effects are larger than at HERA.

PMID- 16606168
TI  - New measurements of Cabibbo-suppressed decays of mesons with the CLEO-c detector.
AB  - Using of data collected with the CLEO-c detector, we report on first observations
      and measurements of Cabibbo-suppressed decays of D mesons in the following six
      decay modes: pi+ pi- pi0 pi0, pi+ pi+ pi- pi- pi0, pi+ pi0 pi0, pi+ pi+ pi- pi0,
      eta pi0, and omega pi+ pi-. Improved branching fraction measurements in eight
      other multipion decay modes are also presented. The measured D --> pi pi rates
      allow us to extract the ratio of isospin amplitudes A(DeltaI = (3/2) / A(DeltaI =
      (1/2)) = 0.420 +/- 0.014(stat) +/- 0.016(syst) and the strong phase shift of
      delta1 = (86.4 +/- 2.8 +/- 3.3) degrees, which is quite large and now more
      precisely determined.

PMID- 16606172
TI  - Observation of a chi(c2)' candidate in gamma gamma --> DD production at belle.
AB  - We report on a search for new resonant states in the process gamma gamma --> DD.
      A candidate C-even charmonium state is observed in the vicinity of 3.93 GeV/c2.
      The production rate and the angular distribution in the gamma gamma center-of
      mass frame suggest that this state is the previously unobserved chi(c2)', the
      2(3)P2 charmonium state.

PMID- 16606175
TI  - Magnetic field-induced spectroscopy of forbidden optical transitions with
      application to lattice-based optical atomic clocks.
AB  - We develop a method of spectroscopy that uses a weak static magnetic field to
      enable direct optical excitation of forbidden electric-dipole transitions that
      are otherwise prohibitively weak. The power of this scheme is demonstrated using
      the important application of optical atomic clocks based on neutral atoms
      confined to an optical lattice. The simple experimental implementation of this
      method--a single clock laser combined with a dc magnetic field--relaxes stringent
      requirements in current lattice-based clocks (e.g., magnetic field shielding and
      light polarization), and could therefore expedite the realization of the
      extraordinary performance level predicted for these clocks. We estimate that a
      clock using alkaline-earth-like atoms such as Yb could achieve a fractional
      frequency uncertainty of well below 10(-17) for the metrologically preferred even
      isotopes.

PMID- 16606173
TI  - Observation of psi(3770) --> pi pi J/psi and measurement of Gamma ee[psi(2S)].
AB  - We observe signals for the decays psi(3770) --> XJ/psi from data acquired with
      the CLEO detector operating at the CESR e+ e- collider with square root of s =
      3773 MeV. We measure the following branching fractions Beta(psi(3770) --> XJ/psi
      and significances: (189 +/- 20 +/- 20) x 10(-5) (11.6sigma) for X = pi+ pi-, (80
      +/- 25 +/- 16) x 10(-5) (3.4sigma) for X = pi0 pi0, and (87 +/- 33 +/- 22) x 10(
      5) (3.5sigma) for X = eta, where the errors are statistical and systematic,
      respectively. The radiative return process e+ e- --> gamma psi(2S) populates the
      same event sample and is used to measure Gamma ee[psi(2S)] = (2.54 +/- 0.03 +/-
      0.11) keV.

PMID- 16606176
TI  - Direct excitation of the forbidden clock transition in neutral 174Yb atoms
      confined to an optical lattice.
AB  - We report direct single-laser excitation of the strictly forbidden (6s2)1S0 <-->
      (6s6p)3P0 clock transition in 174Yb atoms confined to a 1D optical lattice. A
      small (approximately 1.2 mT) static magnetic field was used to induce a nonzero
      electric dipole transition probability between the clock states at 578.42 nm.
      Narrow resonance linewidths of 20 Hz (FWHM) with high contrast were observed,
      demonstrating a resonance quality factor of 2.6 x 10(13). The previously unknown
      ac Stark shift-canceling (magic) wavelength was determined to be 759.35 +/- 0.02
      nm. This method for using the metrologically superior even isotope can be easily
      implemented in current Yb and Sr lattice clocks and can create new clock
      possibilities in other alkaline-earth-like atoms such as Mg and Ca.

PMID- 16606177
TI  - Limits to the polarization for spin-exchange optical pumping of 3He.
AB  - Based on measurements of the temperature dependence of 3He relaxation in a wide
      range of spin-exchange optical pumping cells, we report evidence for a previously
      unrecognized surface relaxation process. The relaxation rate was found to be
      linearly proportional to the alkali-metal density with a slope that exceeds the
      spin-exchange rate, which limits the polarization for current applications,
      including neutron spin filters, polarized targets, and polarized gas magnetic
      resonance imaging. We find that the magnitude of this excess relaxation can vary
      widely between cells, and that the variation is larger for cells of higher
      surface to volume ratio. We have observed 3He polarization as high as 81%, but
      further improvements require understanding the origin of this relaxation.

PMID- 16606179
TI  - Using high-power lasers for detection of elastic photon-photon scattering.
AB  - The properties of four-wave interaction via the nonlinear quantum vacuum is
      investigated. The effect of the quantum vacuum is to generate photons with new
      frequencies and wave vectors, due to elastic photon-photon scattering. An
      expression for the number of generated photons is derived, and using state-of-the
      art laser data it is found that the number of photons can reach detectable
      levels. In particular, the prospect of using the high-repetition Astra Gemini
      system at the Rutherford Appleton Laboratory is discussed. The problem of noise
      sources is reviewed, and it is found that the noise level can be reduced well
      below the signal level. Thus, detection of elastic photon-photon scattering may
      for the first time be achieved.

PMID- 16606180
TI  - Conclusive evidence of an attosecond pulse train observed with the mode-resolved
      autocorrelation technique.
AB  - We report on the direct observation of an attosecond pulse train with a mode
      resolved autocorrelation technique. The chirp among the three harmonic fields is
      specified by analyzing two-photon above-threshold ionization spectra of
      electrons, resulting in a pulse duration that should be shorter than 450 as,
      which is, to our knowledge, the first determination of the chirp in the
      attosecond pulse train with an autocorrelation technique. These results will open
      the way to full characterization of an attosecond pulse train with its envelope.

PMID- 16606178
TI  - Filtering out photonic Fock states.
AB  - Unprecedented optical nonlinearities can be generated probabilistically in simple
      linear-optical networks conditioned on specific measurement outcomes. We describe
      a highly controllable quantum filter for photon number states, which takes
      advantage of such a measurement-induced amplitude nonlinearity. The basis for
      this filter is multiphoton nonclassical interference which we demonstrate for one
      and two-photon states over a wide range of beam splitter reflectivities.
      Specifically, we show that the transmission probability, conditional on a
      specific measurement outcome, can be larger for a two-photon state than a one
      photon state; this is not possible with linear optics alone.

PMID- 16606181
TI  - Generation and weak beam control of two-dimensional multicolored arrays in a
      quadratic nonlinear medium.
AB  - We report on the first experimental observation of 2D multicolored transverse
      arrays in a quadratic nonlinear medium under the pump of two crossly overlapped
      femtosecond beams. The 2D reproducible patterns are caused by cascaded
      noncollinear quadratic nonlinear couplings between the input pulses and quadratic
      spatial solitons originated from spatial breakup of one of the input beams with
      spatial ellipticity. A seed supercontinuum pulse is then diffracted and amplified
      with phase preservation, resulting in the formation of up-converted multicolor 2D
      transverse arrays. By seeding with weak second harmonic pulses, the 2D
      multicolored transverse patterns are suppressed due to weak beam control of the
      induced quadratic spatial solitons.

PMID- 16606183
TI  - Observation of discrete solitons and soliton rotation in optically induced
      periodic ring lattices.
AB  - We report the first experimental demonstration of ring-shaped photonic lattices
      by optical induction and the formation of discrete solitons in such radially
      symmetric lattices. The transition from discrete diffraction to single-channel
      guidance or nonlinear self-trapping of a probe beam is achieved by fine-tuning
      the lattice potential or the focusing nonlinearity. In addition to solitons
      trapped in the lattice center and in different lattice rings, we demonstrate
      controlled soliton rotation in the Bessel-like ring lattices.

PMID- 16606174
TI  - Measurement of two- and three-nucleon short-range correlation probabilities in
      nuclei.
AB  - The ratios of inclusive electron scattering cross sections of 4He, 12C, and 56Fe
      to 3He have been measured at 1 < xB <. At Q2 > 1.4 GeV2, the ratios exhibit two
      separate plateaus, at 1.5 < xB < 2 and at xB > 2.25. This pattern is predicted by
      models that include 2- and 3-nucleon short-range correlations (SRC). Relative to
      A = 3, the per-nucleon probabilities of 3-nucleon SRC are 2.3, 3.1, and 4.4 times
      larger for A = 4, 12, and 56. This is the first measurement of 3-nucleon SRC
      probabilities in nuclei.

PMID- 16606184
TI  - Self-optimization of optical confinement in an ultraviolet photonic crystal slab
      laser.
AB  - We studied numerically and experimentally the effects of structural disorder on
      the performance of ultraviolet photonic crystal slab lasers. Optical gain
      selectively amplifies the high-quality modes of the passive system. For these
      modes, the in-plane and out-of-plane leakage rates may be automatically balanced
      in the presence of disorder. The spontaneous optimization of in-plane and out-of
      plane confinement of light in a photonic crystal slab may lead to a reduction of
      the lasing threshold.

PMID- 16606182
TI  - Dynamical control: comparison of map and continuous-flow approaches.
AB  - Continuous and pulsed forms of control of a multistable system are compared
      directly, both theoretically and numerically, taking as an example the switching
      of a periodically driven class-B laser between its stable and unstable pulsing
      regimes. It is shown that continuous control is the more energy efficient. This
      result is illuminated by making use of the close correspondence that exists
      between the problems of energy-optimal control and the stability of a steady
      state.

PMID- 16606185
TI  - High-rayleigh-number convection in a vertical channel.
AB  - We measure the relation between convective heat flux and temperature gradient in
      a vertical channel filled with water, the average vertical mass flux being zero.
      Compared to the classical Rayleigh-Benard case, this situation has the advantage
      of avoiding plates and, thus, their neighborhood, in which is usually
      concentrated most of the temperature gradient. Consequently, inertial processes
      should control the convection, with poor influence of the viscosity. This idea
      gives a good account of our observations, if we consider that a natural vertical
      length, different from the channel width, appears. Our results also suggest that
      heat fluxes can be deduced from velocity measurements in free convective flows.
      This confers to our results a wide range of applications.

PMID- 16606186
TI  - Physical mechanism of the two-dimensional inverse energy cascade.
AB  - We study the physical mechanisms of the two-dimensional inverse energy cascade
      using theory, numerics, and experiment. Kraichnan's prediction of a -5/3 spectrum
      with constant, negative energy flux is verified in our simulations of 2D Navier
      Stokes equations. We observe a similar but shorter range of inverse cascade in
      laboratory experiments. Our theory predicts, and the data confirm, that inverse
      cascade results mainly from turbulent stress proportional to small-scale strain
      rotated by 45 degrees. This "skew-Newtonian" stress is explained by the
      elongation and thinning of small-scale vortices by large-scale strain which
      weakens their velocity and transfers their energy upscale.

PMID- 16606187
TI  - Microevaporators for kinetic exploration of phase diagrams.
AB  - We use pervaporation-based microfluidic devices to concentrate species in aqueous
      solutions with spatial and temporal control of the process. Using experiments and
      modeling, we quantitatively describe the advection-diffusion behavior of the
      concentration field of various solutions (electrolytes, colloids, etc.) and
      demonstrate the potential of these devices as universal tools for the kinetic
      exploration of the phases and textures that form upon concentration.

PMID- 16606188
TI  - Consistent theory of turbulent transport in two-dimensional magnetohydrodynamics.
AB  - A theory of turbulent transport is presented in two-dimensional
      magnetohydrodynamics with background shear and magnetic fields. We provide
      theoretical predictions for the transport of magnetic flux, momentum, and
      particles and turbulent intensities, which show stronger reduction compared with
      the hydrodynamic case, with different dependences on shearing rate, magnetic
      field, and values of viscosity, Ohmic diffusion, and particle diffusivity. In
      particular, particle transport is more severely suppressed than momentum
      transport, effectively leading to a more efficient momentum transport. The role
      of magnetic fields in quenching transport without altering the amplitude of flow
      velocity and in inhibiting the generation of shear flows is elucidated.
      Implications of the results are discussed.

PMID- 16606189
TI  - Harmonic lasing in a free-electron-laser amplifier.
AB  - A method is demonstrated that allows a planar wiggler high-gain Free-Electron
      Laser (FEL) amplifier to lase so that the interaction with an odd harmonic of the
      radiation field dominates that of the fundamental. This harmonic lasing of the
      FEL is achieved by disrupting the electron interaction with the usually dominant
      fundamental while allowing that of a harmonic interaction to evolve unhindered.
      The disruption is achieved by a series of relative phase changes between the
      electrons and the ponderomotive potentials of both the fundamental and harmonic
      fields. Such phase changes are relatively easy to implement and some current FEL
      designs would require little or no structural modification to test the scheme.

PMID- 16606190
TI  - Transient electrostatic fields and related energetic proton generation with a
      plasma fiber.
AB  - We observe a hollow structure and a fine ring in the proton images from a
      petawatt scale laser interaction with a "cone-fiber" target. The protons related
      to the hollow structure are accelerated from the cone-tip surface and deflected
      later by a radial electric field surrounding the fiber. Those associated with the
      fine ring are accelerated from the fiber surface by this radial electric field.
      This field is found to decay exponentially within 3 ps from about 5 x 10(12) V/m.
      Two-dimensional particle-in-cell simulations produce similar proton angular
      distributions.

PMID- 16606191
TI  - Impurity pinch from a ratchet process.
AB  - A ratchet-type average velocity is shown to appear for test particles moving in a
      stochastic potential and a magnetic field that is space dependent. This is a
      possible explanation for impurity behavior in tokamak plasmas.

PMID- 16606192
TI  - Production of dense plasmas with sub-10-fs laser pulses.
AB  - Close to solid state density plasmas with peak electron temperatures of about 190
      eV have been generated with sub-10-fs laser pulses incident on solid targets.
      Extreme ultraviolet (XUV) spectroscopy is used to investigate the K shell
      emission from the plasma. In the spectra, a series limit for the H- and He-like
      resonance lines becomes evident which is explained by pressure ionization in the
      dense plasma. The spectra are consistent with computer simulations calculating
      the XUV emission and the expansion of the plasma.

PMID- 16606193
TI  - An exact magnetic-moment invariant of charged-particle gyromotion.
AB  - For the motion of a charged particle in a uniform, time-dependent axial magnetic
      field B(t)e(z), it is shown that there is an exact magnetic-moment invariant of
      the particle dynamics M, to which the adiabatic magnetic-moment invariant mu =
      mv2 perpendicular/2B is asymptotic when the time scale of the magnetic field
      variation is much slower than the gyroperiod. The connection between the exact
      invariant M and the adiabatic invariant mu enables us to characterize in detail
      the robustness of the adiabatic magnetic-moment invariant mu.

PMID- 16606194
TI  - Vortex multiplication in applied flow: A precursor to superfluid turbulence.
AB  - A surface-mediated process is identified in 3He-B which generates vortices at a
      roughly constant rate. It precedes a faster form of turbulence where intervortex
      interactions dominate. This precursor becomes observable when vortex loops are
      introduced in low-velocity rotating flow at sufficiently low mutual friction
      dissipation at temperatures below 0.5Tc. Our measurements indicate that the
      formation of new loops is associated with a single vortex interacting in the
      applied flow with the sample boundary. Numerical calculations show that the
      single-vortex instability arises when a helical Kelvin wave expands from a
      reconnection kink at the wall and then intersects again with the wall.

PMID- 16606195
TI  - Hardness of covalent and ionic crystals: first-principle calculations.
AB  - A new concept, the strength of bond, and a new form expressing the hardness of
      covalent and ionic crystals are presented. Hardness is expressed by means of
      quantities inherently coupled to the atomistic structure of matter, and,
      therefore, hardness can be determined by first-principles calculations. Good
      agreement between theory and experiment is observed in the range of 2 orders of
      magnitude. It is shown that a lower coordination number of atoms results in
      higher hardness, contrary to common opinion presented in general literature.

PMID- 16606169
TI  - Search for Higgs bosons decaying to bb and produced in association with W bosons
      in pp collisions at square root of s = 1.96 TeV.
AB  - We present a search for Higgs bosons decaying into bb and produced in association
      with W bosons in pp collisions at square root of s = 1.96 TeV. This search uses
      320 pb(-1) of the data set accumulated by the upgraded Collider Detector at
      Fermilab. Events are selected that have a high-transverse momentum electron or
      muon, missing transverse energy, and two jets, at least one of which is
      consistent with the hadronization of a b quark. Both the number of events and the
      dijet mass distribution are consistent with standard model background
      expectations, and we set 95% confidence level upper limits on the production
      cross section times branching ratio for the Higgs boson or any new particle with
      similar decay kinematics. These upper limits range from 10 pb for mH = 110 GeV/c2
      to 3 pb for mH = 150 GeV/c2.

PMID- 16606197
TI  - Nonlinear ripple dynamics on amorphous surfaces patterned by ion beam sputtering.
AB  - Erosion by ion-beam sputtering (IBS) of amorphous targets at off-normal incidence
      frequently produces a (nanometric) rippled surface pattern, strongly resembling
      macroscopic ripples on aeolian sand dunes. A suitable generalization of continuum
      descriptions of the latter allows us to describe theoretically for the first time
      the main nonlinear features of ripple dynamics by IBS, namely, wavelength
      coarsening and nonuniform translation velocity, that agree with similar results
      in experiments and discrete models. These properties are seen to be the
      anisotropic counterparts of in-plane ordering and (interrupted) pattern
      coarsening in IBS experiments on rotating substrates and at normal incidence.

PMID- 16606196
TI  - Nonequilibrium steady states in sheared binary fluids.
AB  - We simulate by lattice Boltzmann the steady shearing of a binary fluid mixture
      undergoing phase separation with full hydrodynamics in two dimensions. Contrary
      to some theoretical scenarios, a dynamical steady state is attained with finite
      domain lengths L(x,y) in the directions (x,y) of velocity and velocity gradient.
      Apparent scaling exponents are estimated as Lx approximately gamma (-2/3) and Ly
      approximately gamma(-3/4). We discuss the relative roles of diffusivity and
      hydrodynamics in attaining steady state.

PMID- 16606171
TI  - Evidence for the exclusive decay B(c)+- --> J/psi pi+- and measurement of the
      mass of the B(c)+- meson.
AB  - We report the first evidence for a fully reconstructed decay mode of the B(c)+-
      meson in the channel B(c)+- --> J/psi pi+-, with J/psi --> mu+ mu-. The analysis
      is based on an integrated luminosity of 360 pb(-1) in pp collisions at 1.96 TeV
      center of mass energy collected by the Collider Detector at Fermilab. We observe
      14.6 +/- 4.6 signal events with a background of 7.1 +/- 0.9 events, and a fit to
      the J/psi pi+-mass spectrum yields a B(c)+- mass of 6285.7 +/- 5.3(stat) +/-
      1.2(syst) MeV/c2. The probability of a peak of this magnitude occurring by random
      fluctuation in the search region is estimated as 0.012%.

PMID- 16606198
TI  - Orientation of ordered structures of cytosine and cytidine -monophosphate
      adsorbed at Au(110)/liquid interfaces.
AB  - It is demonstrated using reflection anisotropy spectroscopy that the adsorption
      of cytosine and cytidine -monophosphate at the Au(110) 1 x 2/electrolyte
      interface gives rise to ordered structures in which the base is oriented vertical
      to the surface and parallel to the [110] axis of the Au(110) plane.

PMID- 16606199
TI  - High-resolution resonance measurements of the physisorption interaction.
AB  - Narrow selective adsorption resonances, with line widths given by the natural
      lifetime of the intermediate resonance state, have been observed directly in the
      angular distributions of Ne nozzle beams diffracted from a 20 K Cu(110) surface.
      Using beams of 20Ne and 22Ne isotopes we show that this high-resolution mode of
      resonance detection permits, even in a case of a small isotope effect, unique
      assignment of bound level sequences compatible with a single gas-surface
      potential curve.

PMID- 16606200
TI  - Bimodal growth of Au on SrTiO3(001).
AB  - We have investigated the vapor phase growth of Au on SrTiO3(001)-(2 x 1)
      substrates by UHV scanning tunneling microscopy. Submonolayer (ML) coverages
      below 300 degrees C wet the surface as disordered metastable 2D islands. Beyond
      0.75 ML fcc nanocrystals with a (111) interface are nucleated and ripen by
      dewetting the surrounding layer. Some multiply twinned fivefold symmetric
      clusters are also created. Above 400 degrees C dewetting occurs for all coverages
      and the surface is only populated by nanocrystals and fivefold clusters. A planar
      ground state configuration for small Au clusters and a higher interface energy
      for crystals than for wetted 2D ML films explains these results.

PMID- 16606201
TI  - Oscillatory dissipation of a simple confined liquid.
AB  - We present a sensitive measurement of the dissipation and the effective viscosity
      of a simple confined liquid (octamethylcyclotetrasiloxane) using an atomic force
      microscope. The experimental data show that the damping and the effective
      viscosity increase and present oscillations as the gap between the cantilever tip
      and the surface is diminished. To our knowledge, the damping and the viscosity
      modulation are reported here with such good accuracy for the first time. Such an
      experimental result is different from what has been reported earlier where only a
      continuous increase of the damping and the viscosity are observed.

PMID- 16606202
TI  - Self-assembled nanofold network formation on layered crystal surfaces during
      metal intercalation.
AB  - We study the formation of planar network nanostructures, which develop during
      metal deposition on initially smooth surfaces of layered compounds. Using in situ
      low-energy electron microscopy for dynamic observation and high-resolution
      transmission electron microscopy for structure analysis, we have observed the
      rapid formation of hexagonal networks of linear "nanofolds" with prismatic
      cavities on top of layered VSe2 crystals. Their formation results from relaxation
      of compressive strains which build up during Cu intercalation into a thin surface
      layer.

PMID- 16606203
TI  - Self-localization of composite spin-lattice polarons.
AB  - Self-localization of holes in the Holstein t-J model is studied in the adiabatic
      limit using exact diagonalization and the retraceable path approximation. It is
      shown that the critical electron-phonon coupling lambda c decreases with
      increasing J and that this behavior is determined mainly by the incoherent rather
      than by the coherent motion of the hole. The obtained spin correlation functions
      in the localized region can be understood within a percolation picture where
      antiferromagnetic order can persist up to a substantial hole doping. These
      results restrict the possibility of self-localization of holes in lightly doped
      cuprates.

PMID- 16606204
TI  - Giant anisotropy of Zeeman splitting of quantum confined acceptors in Si/Ge.
AB  - Shallow acceptor levels in Si/Ge/Si quantum well heterostructures are
      characterized by resonant-tunneling spectroscopy in the presence of high magnetic
      fields. In a perpendicular magnetic field we observe a linear Zeeman splitting of
      the acceptor levels. In an in-plane field, on the other hand, the Zeeman
      splitting is strongly suppressed. This anisotropic Zeeman splitting is shown to
      be a consequence of the huge light-hole--heavy-hole splitting caused by a large
      biaxial strain and a strong quantum confinement in the Ge quantum well.

PMID- 16606205
TI  - Can Competition between the crystal field and the Kondo effect cause non-Fermi
      liquid-like behavior?
AB  - The recently reported unusual behavior of the static and dynamical magnetic
      susceptibility as well as the specific heat in Ce(1-x)La(x)Ni9Ge4 has raised the
      question of a possible non-Fermi-liquid ground state in this material. We argue
      that for a consistent physical picture the crystal-field splitting of two low
      lying magnetic doublets of the Ce 4f-shell must be taken into account.
      Furthermore, we show that for a splitting of the order of the low temperature
      scale T* of the system a crossover behavior between an SU(4) and an SU(2) Kondo
      effect is found. The screening of the two doublets occurs on different
      temperature scales leading to a different behavior of the magnetic susceptibility
      and the specific heat at low temperatures. The experimentally accessible
      temperature regime down to 50 mK still lies in the extended crossover regime into
      a strong-coupling Fermi-liquid fixed point.

PMID- 16606206
TI  - Ab initio prediction of conduction band spin splitting in zinc blende
      semiconductors.
AB  - We use a recently developed self-consistent GW approximation to present
      systematic ab initio calculations of the conduction band spin splitting in III-V
      and II-VI zinc blende semiconductors. The spin-orbit interaction is taken into
      account as a perturbation to the scalar relativistic Hamiltonian. These are the
      first calculations of conduction band spin splittings based on a quasiparticle
      approach; and because the self-consistent GW scheme accurately reproduces the
      relevant band parameters, it is expected to be a reliable predictor of spin
      splittings. The results are compared to the few available experimental data and a
      previous calculation based on a model one-particle potential. We also briefly
      address the widely used k x p parametrization in the context of these results.

PMID- 16606207
TI  - Spontaneous formation of vanadium "molecules" in a geometrically frustrated
      crystal: AlV2O4.
AB  - We investigated the charge-ordered (CO) state in spinel AlV2O4 by electron
      diffraction, synchrotron x-ray diffraction, and magnetic measurements. It was
      found that the CO structure appearing below 700 K is characterized by the
      formation of V clusters (heptamers), each of which is consisting of 7 vanadium
      atoms and is in a spin-singlet state as a total. Theoretical consideration
      indicates that this unique molecularlike V heptamer is stabilized by a strong
      bonding of vanadium t(2g) orbitals.

PMID- 16606208
TI  - Doped spin liquid: Luttinger sum rule and low temperature order.
AB  - We analyze a model of two-leg Hubbard ladders weakly coupled by interladder
      tunneling. At half filling a semimetallic state with small Fermi pockets is
      induced beyond a threshold tunneling strength. The sign changes in the single
      electron Green's function relevant for the Luttinger sum rule now take place at
      surfaces with both zeros and infinities with important consequences for the
      interpretation of angle-resolved photoemission spectroscopy experiments. Residual
      interactions between electron and holelike quasiparticles cause a transition to
      long range order at low temperatures. The theory can be extended to small doping
      leading to superconducting order.

PMID- 16606209
TI  - Charge-transport regime of crystalline organic semiconductors: diffusion limited
      by thermal off-diagonal electronic disorder.
AB  - We propose that the electron transport in crystalline organic semiconductors at
      room temperature (RT) is neither polaronic nor a combination of thermally
      activated hopping and polaronic transport, as previously thought. Thermal
      molecular motions cause large fluctuations in the intermolecular transfer
      integrals that, in turn, localize the charge carrier. This effect destroys the
      translational symmetry of the electronic Hamiltonian and makes the band
      description inadequate for RT organic crystals. We used a one-dimensional
      semiclassical model to compute the (temperature dependent) charge carrier
      mobility in the presence of thermal fluctuations of the electronic Hamiltonian.
      This transport mechanism explains several contrasting experimental observations
      pointing sometimes to a delocalized "bandlike" transport and sometimes to the
      existence of strongly localized charge carriers.

PMID- 16606210
TI  - Microwave-induced dephasing in one-dimensional metal wires.
AB  - We report on the effect of monochromatic microwave (MW) radiation on the weak
      localization corrections to the conductivity of quasi-one-dimensional silver
      wires. Because of the improved electron cooling in the wires, the MW-induced
      dephasing is observed without a concomitant overheating of electrons over wide
      ranges of the MW power P(MW) and frequency f. The observed dependences of the
      conductivity and MW-induced dephasing rate on P(MW) and f are in agreement with
      the theory by Altshuler, Aronov, and Khmelnitsky [Solid State Commun. 39, 619
      (1981)]. Our results suggest that in the low-temperature experiments with 1D
      wires, saturation of the temperature dependence of the dephasing time can be
      caused by an MW electromagnetic noise with a sub-pW power.

PMID- 16606211
TI  - Resonant intrinsic spin hall effect in p-type GaAs quantum well structure.
AB  - We study intrinsic spin Hall effect in p-type GaAs quantum well structure
      described by Luttinger Hamiltonian and a Rashba spin-orbit coupling arising from
      the structural inversion symmetry breaking. The Rashba term induces an energy
      level crossing in the lowest heavy hole subband, which gives rise to a resonant
      spin Hall conductance. The resonance may be used to identify the intrinsic spin
      Hall effect in experiments.

PMID- 16606212
TI  - Full counting statistics for a single-electron transistor: nonequilibrium effects
      at intermediate conductance.
AB  - We evaluate the current distribution for a single-electron transistor with
      intermediate strength tunnel conductance. Using the Schwinger-Keldysh approach
      and the drone (Majorana) fermion representation, we account for the
      renormalization of system parameters. Nonequilibrium effects induce a lifetime
      broadening of the charge-state levels, which suppress large current fluctuations.

PMID- 16606213
TI  - Local pressure-induced metallization of a semiconducting carbon nanotube in a
      crossed junction.
AB  - The electronic and vibrational density of states of a semiconducting carbon
      nanotube in a crossed junction was investigated by elastic and inelastic scanning
      tunneling spectroscopy. The strong radial compression of the nanotube at the
      junction induces local metallization spatially confined to a few nanometers. The
      local electronic modifications are correlated with the observed changes in the
      radial breathing and G band phonon modes, which react very sensitively to local
      mechanical deformation. In addition, the experiments reveal the crucial
      contribution of the image charges to the contact potential at nanotube-metal
      interfaces.

PMID- 16606214
TI  - Landau-level degeneracy and quantum Hall effect in a graphite bilayer.
AB  - We derive an effective two-dimensional Hamiltonian to describe the low-energy
      electronic excitations of a graphite bilayer, which correspond to chiral
      quasiparticles with a parabolic dispersion exhibiting Berry phase 2pi. Its high
      magnetic-field Landau-level spectrum consists of almost equidistant groups of
      fourfold degenerate states at finite energy and eight zero-energy states. This
      can be translated into the Hall conductivity dependence on carrier density,
      sigma(xy)(N), which exhibits plateaus at integer values of 4e2/h and has a double
      8e2/h step between the hole and electron gases across zero density, in contrast
      to (4n + 2)e2/h sequencing in a monolayer.

PMID- 16606215
TI  - Uniform mixing of high-Tc superconductivity and antiferromagnetism on a single
      CuO2 plane of a Hg-based five-layered cuprate.
AB  - We report a site selective Cu-NMR study on underdoped Hg-based five-layered high
      Tc cuprate HgBa2Ca4CU5O(12+delta) with a Tc = 72 K. Antiferromagnetism (AFM) has
      been found to take place at T(N) = 290 K, exhibiting a large antiferromagnetic
      moment of 0.67-0.69 microB at three inner planes (IP). This value is comparable
      to the values reported for nondoped cuprates, suggesting that the IP may be in a
      nearly nondoped regime. Most surprisingly, the AFM order is also detected with
      M(AFM)(OP) = 0.1 microB even at two outer planes (OP) that are responsible for
      the onset of superconductivity (SC). The high-Tc SC at Tc = 72 K can uniformly
      coexist on a microscopic level with the AFM at OP's. This is the first
      microscopic evidence for the uniform mixed phase of AFM and SC on a single CuO2
      plane in a simple environment without any vortex lattice and/or stripe order.

PMID- 16606216
TI  - Nucleation and collapse of the superconducting phase in type-I superconducting
      films.
AB  - The phase transition between the intermediate and normal states in type-I
      superconducting films is investigated using magneto-optical imaging. Magnetic
      hysteresis with different transition fields for collapse and nucleation of
      superconducting domains is found. This is accompanied by topological hysteresis
      characterized by the collapse of circular domains and the appearance of lamellar
      domains. Magnetic hysteresis is shown to arise from supercooled and superheated
      states. Domain-shape instability resulting from long-range magnetic interaction
      accounts well for topological hysteresis.

PMID- 16606217
TI  - First-order metal-insulator transitions in manganites: are they universal?
AB  - Conductivity data for La(2-2x)Sr(1+2xMn2O7 (x = 0.6) show a first-order
      transition from an orbital- or charge-ordered insulator to a metal as the
      temperature falls below approximately 160 K. The change in conductivity is 100
      times larger than that seen previously in any single-phase manganite in zero
      field. The metallic low-temperature state is similar to x = 0.58, but x = 0.58
      shows no evidence of orbital or charge order. This result supports a conclusion
      that strongly coupled magnetic-conductive transitions are first order.

PMID- 16606218
TI  - Unified picture of ferromagnetism, quasi-long-range order, and criticality in
      random-field models.
AB  - By applying the recently developed nonperturbative functional renormalization
      group (FRG) approach, we study the interplay between ferromagnetism, quasi-long
      range order (QLRO), and criticality in the d-dimensional random-field O(N) model
      in the whole (N, d) diagram. Even though the "dimensional reduction" property
      breaks down below some critical line, the topology of the phase diagram is found
      similar to that of the pure O(N) model, with, however, no equivalent of the
      Kosterlitz-Thouless transition. In addition, we obtain that QLRO, namely, a
      topologically ordered "Bragg glass" phase, is absent in the 3-dimensional random
      field XY model. The nonperturbative results are supplemented by a perturbative
      FRG analysis to two loops around d = 4.

PMID- 16606219
TI  - Magnon decay in gapped quantum spin systems.
AB  - In the continuum O(3) sigma-model description of gapped spin systems, S = 1
      magnons can only decay into three lower energy magnons. We argue that the
      symmetry of the quantum spin Hamiltonian often allows decay into two magnons, and
      compute this decay rate in model systems. Two-magnon decay is present in Haldane
      gap S = 1 spin chains, even though it cannot be induced by any allowed term
      written in powers and gradients of the sigma-model field. We compare our results
      with recent measurements of Stone et al. on a two-dimensional spin system.

PMID- 16606220
TI  - Metallic spin-liquid behavior of the geometrically frustrated Kondo lattice.
AB  - Strongly frustrated magnetism of the metallic pyrochlore oxide Pr2Ir2O7 has been
      revealed by single crystal study. While Pr 4f moments have an antiferromagnetic
      RKKY interaction energy scale of /T*/ = 20 K mediated by Ir 5d-conduction
      electrons, no magnetic long-range order is found except for partial spin freezing
      at 120 mK. Instead, the Kondo effect, including a lnT dependence in the
      resistivity, emerges and leads to a partial screening of the moments below /T*/.
      Our results indicate that the underscreened moments show spin-liquid behavior
      below a renormalized correlation scale of 1.7 K.

PMID- 16606221
TI  - Origin of ferromagnetism and its pressure and doping dependence in Tl2Mn2O7.
AB  - Using the Nth order muffin-tin obital downfolding technique, we investigate the
      origin of ferromagnetism in pyrochlore Tl2Mn2O7. It is found to be driven by a
      hybridization induced spin polarization of delocalized charge carriers derived
      from Tl-s and O-p states. The mean-field estimate of the ferromagnetic transition
      temperature Tc estimated using computed exchange integrals are found to be in
      good agreement with measurements. We find an enhancement of Tc for moderate
      doping with nonmagnetic Sb and a suppression of Tc upon application of pressure,
      both in agreement with experimental findings.

PMID- 16606222
TI  - Electron dynamics of silicon surface states: second-harmonic hole burning on
      Si(111)-(7 x 7).
AB  - We report the first all-optical study of homogeneous linewidths of surface
      excitations by the spectral-hole-burning technique with surface-specific second
      harmonic generation as a probe. Measurement of transient spectral holes induced
      by a 100 fs pump pulse in excitations of the surface dangling-bond states of
      Si(111)-(7 x 7) led to a pump-fluence-dependent homogeneous linewidth as broad as
      approximately 100 meV or a dephasing time as short as 15 fs. The hole-burning
      spectra also revealed a strong coupling between the localized dangling-bond
      states and the associated surface phonon mode at 570 cm(-1). Carrier-carrier
      scattering was responsible for the linear dependence of the dephasing rate on
      pump fluence, and the carrier screening effect appeared to be weak.

PMID- 16606223
TI  - Density matrix tomography through sequential coherent optical rotations of an
      exciton qubit in a single quantum dot.
AB  - We demonstrate single qubit density matrix tomography in a single semiconductor
      quantum dot system through consecutive phase sensitive rotations of the qubit via
      ultrafast coherent optical excitations. The result is important for quantifying
      gate operations in quantum information processing in the quantum dot systems as
      well as demonstrating consecutive arbitrary qubit rotations.

PMID- 16606224
TI  - Mechanisms of high-order perturbative photoemission from Cu(001).
AB  - We observed high-order 2- to 4-photon photoemission and above threshold
      photoemission (ATP) processes with 3.07 eV light from the Cu(001) surface. The
      intensity of 3-photon photoemission via excitation through the n = 1 image
      potential state significantly exceeded that of the 2-photon process. The ATP
      occurs either via single photon transitions from the image potential resonances
      above the vacuum level or by multiphoton transitions from image potential states
      below the vacuum level. The experimental ratio of the m- to (m + 1)-photon
      process yields is sensitive to the electronic band structure of the solid.

PMID- 16606226
TI  - Coupling hydrophobicity, dispersion, and electrostatics in continuum solvent
      models.
AB  - An implicit solvent model is presented that couples hydrophobic, dispersion, and
      electrostatic solvation energies by minimizing the system Gibbs free energy with
      respect to the solvent volume exclusion function. The solvent accessible surface
      is the output of the theory. The method is illustrated with the solvation of
      simple solutes on different length scales and captures the sensitivity of
      hydration to the particular form of the solute-solvent interactions in agreement
      with recent computer simulations.

PMID- 16606227
TI  - Light scattering and phase behavior of lysozyme-poly(ethylene glycol) mixtures.
AB  - Measurements of liquid-liquid phase transition temperatures (cloud points) of
      mixtures of a protein (lysozyme) and a polymer, poly(ethylene glycol) (PEG) show
      that the addition of low molecular weight PEG stabilizes the mixture whereas high
      molecular weight PEG was destabilizing. We demonstrate that this behavior is
      inconsistent with an entropic lysozyme-PEG depletion interaction and suggest that
      an energetic lysozyme-PEG attraction is responsible. In order to independently
      characterize the lysozyme-PEG interactions, light scattering experiments on the
      same mixtures were performed to measure second and third virial coefficients.
      These measurements indicate that PEG induces repulsion between lysozyme
      molecules, contrary to the depletion prediction. Furthermore, it is shown that
      third virial terms must be included in the mixture's free energy in order to
      qualitatively capture our data.

PMID- 16606228
TI  - Anomalous vibrational dispersion in holographically trapped colloidal arrays.
AB  - Colloidal spheres localized in an array of harmonic wells form a thermally
      excited, viscously damped dynamical system capable of supporting propagating
      elastic waves. Experimentally realized with micrometer-scale polystyrene spheres
      localized in a line of holographic optical traps, the hydrodynamically coupled
      array's behavior is quantitatively explained by a model based on the Oseen
      superposition approximation. The spheres' purely dissipative coupling is
      predicted to mediate a crossover to a regime of underdamped propagating elastic
      waves with uniformly negative group velocities that has yet to be verified
      experimentally.

PMID- 16606229
TI  - Stress-dependent elasticity of composite actin networks as a model for cell
      behavior.
AB  - Networks of filamentous actin cross-linked with the actin-binding protein filamin
      A exhibit remarkable strain stiffening leading to an increase in differential
      elastic modulus by several orders of magnitude over the linear value. The
      variation of the frequency dependence of the differential elastic and loss moduli
      as a function of prestress is consistent with that observed in living cells,
      suggesting that cell elasticity is always measured in the nonlinear regime, and
      that prestress is an essential control parameter.

PMID- 16606230
TI  - Interface instability in shear-banding flow.
AB  - We report on the spatiotemporal dynamics of the interface in shear-banding flow
      of a wormlike micellar system (cetyltrimethylammonium bromide and sodium nitrate
      in water) during a start-up experiment. Using the scattering properties of the
      induced structures, we demonstrate the existence of an instability of the
      interface between bands along the vorticity direction. Different regimes of
      spatiotemporal dynamics of the interface are identified along the stress plateau.
      We build a model based on the flow symmetry which qualitatively describes the
      observed patterns.

PMID- 16606231
TI  - Optimal cell approach to osmotic properties of finite stiff-chain
      polyelectrolytes.
AB  - We propose a self-consistent geometry optimized cell model approach to study
      osmotic properties of stiff-chain polyelectrolyte solutions. In contrast with the
      usual monotonic Poisson-Boltzmann prediction, the cell model predicts the correct
      nonmonotonic dependence of the osmotic coefficient on concentration. A lower
      degree of polymerization is found to reduce significantly the counterion
      condensation in a typical dilute strong polyelectrolyte. The results agree
      quantitatively with simulations of a corresponding many-body bulk system up to a
      dense semidilute regime.

PMID- 16606232
TI  - Cyclic motion of a grafted polymer under shear flow.
AB  - The long-time dynamics of a single end-tethered chain under shear flow are
      studied using molecular and Brownian dynamics simulations of a flexible polymer.
      As observed in previous experiments with tethered DNA [Phys. Rev. Lett. 84, 4769
      (2000)], under a flow sheared at constant rate the chain performs a cyclic
      motion. But, contrary to what has been previously suggested, a well-defined
      characteristic period exists and it is clearly revealed in the cross spectra of
      the chain extension along flow and gradient directions. The main cycling time
      scales like the time needed to stretch the polymer by convection, being about 10
      times the relaxation time of the chain in flow. This coherent recursive motion
      introduces long memory in the fluid and suggests resonance effects under periodic
      external forcing.

PMID- 16606233
TI  - Transmission electron microscopy imaging of individual functional groups of
      fullerene derivatives.
AB  - Mobility and reactivity of the functionalized fullerenes with pyrrolidine (C60
      C3NH7) incorporated in single-wall carbon nanotubes were examined by high
      resolution transmission electron microscopy. An individual functional group
      attached to each fullerene cage is unambiguously visualized. This provides a
      direct evidence for the functionalized structure on a single-molecular basis. A
      rotational motion of the incorporated molecules tends to occur during the
      observation and, consequently, each fullerene molecule is likely to stand facing
      its functionalized group towards the nanotube wall. A fine structure analysis of
      electron energy-loss spectra for the nitrogen K(1s) edge shows a considerable
      change in the nitrogen chemical state and suggests a strong tube-fullerene
      interaction.

PMID- 16606235
TI  - Volume-exclusion effects in tethered-particle experiments: bead size matters.
AB  - We give a theoretical analysis of bead motion in tethered-particle experiments, a
      single-molecule technique that has been used to explore the dynamics of a variety
      of macromolecules of biological interest. Our analysis reveals that the proximity
      of the tethered bead to a nearby surface gives rise to a volume-exclusion effect,
      resulting in an entropic stretching-force on the molecule that changes its
      statistical properties. In addition, volume exclusion brings about intriguing
      scaling relations between key observables (statistical moments of the bead) and
      parameters such as bead size and contour length of the molecule. We present
      analytic and numerical results for these effects in both flexible and
      semiflexible tethers. Finally, our results give a precise, experimentally
      testable prediction for the probability distribution of the bead center measured
      from the polymer attachment point.

PMID- 16606236
TI  - Cochlea's graded curvature effect on low frequency waves.
AB  - In the ear, sound waves are processed by a membrane of graded mechanical
      properties that resides in the fluid-filled spiral cochlea. The role of stiffness
      grading as a Fourier analyzer is well known, but the role of the curvature has
      remained elusive. Here, we report that increasing curvature redistributes wave
      energy density towards the cochlea's outer wall, affecting the shape of waves
      propagating on the membrane, particularly in the region where low frequency
      sounds are processed.

PMID- 16606237
TI  - System of mobile agents to model social networks.
AB  - We propose a model of mobile agents to construct social networks, based on a
      system of moving particles by keeping track of the collisions during their
      permanence in the system. We reproduce not only the degree distribution,
      clustering coefficient, and shortest path length of a large database of empirical
      friendship networks recently collected, but also some features related with their
      community structure. The model is completely characterized by the collision rate,
      and above a critical collision rate we find the emergence of a giant cluster in
      the universality class of two-dimensional percolation. Moreover, we propose
      possible schemes to reproduce other networks of particular social contacts,
      namely, sexual contacts.

PMID- 16606238
TI  - Comment on "Instability and entanglement of the ground state of the Dicke model".

PMID- 16606240
TI  - Comment on "Yield of singlet excitons in organic light-emitting devices: a double
      modulation photoluminescence-detected magnetic resonance study".

PMID- 16606242
TI  - Comment on "Intrinsic low temperature paramagnetism in B-DNA".

PMID- 16606244
TI  - Probing number squeezing of ultracold atoms across the superfluid-Mott insulator
      transition.
AB  - The evolution of on-site number fluctuations of ultracold atoms in optical
      lattices is experimentally investigated by monitoring the suppression of spin
      changing collisions across the superfluid-Mott insulator transition. For low atom
      numbers, corresponding to an average filling factor close to unity, large on-site
      number fluctuations are necessary for spin-changing collisions to occur. The
      continuous suppression of spin-changing collisions is thus direct evidence for
      the emergence of number-squeezed states. In the Mott insulator regime, we find
      that spin-changing collisions are suppressed until a threshold atom number,
      consistent with the number where a Mott plateau with doubly occupied sites is
      expected to form.

PMID- 16606245
TI  - Entangled photon holes.
AB  - Most experimental demonstrations of entanglement require nonclassical states and
      correlated measurements of single-photon detection events. It is shown here that
      entanglement can produce a large decrease in the rate of two-photon absorption
      for a classical input state that can be observed using classical detectors. These
      effects can be interpreted as being due to the creation of entangled photon holes
      that are somewhat analogous to the holes of semiconductor theory.

PMID- 16606246
TI  - Vortices in superfluid fermi gases through the BEC to BCS crossover.
AB  - We have analyzed a single vortex at T=0 in a 3D superfluid atomic Fermi gas
      across a Feshbach resonance. On the BCS side, the order parameter varies on two
      scales: k(F)(-1)and the coherence length xi, while only variation on the scale of
      xi is seen away from the BCS limit. The circulating current has a peak value jmax
      which is a nonmonotonic function of 1/k(F)a(s) implying a maximum critical
      velocity approximately v(F) at unitarity. The number of fermionic bound states in
      the core decreases as we move from the BCS to the BEC regime. Remarkably, a bound
      state branch persists even on the BEC side reflecting the composite nature of
      bosonic molecules.

PMID- 16606247
TI  - Spin 1/2 fermions in the unitary regime: a superfluid of a new type.
AB  - We study, in a fully nonperturbative calculation, a dilute system of spin 1/2
      interacting fermions, characterized by an infinite scattering length at finite
      temperatures. Various thermodynamic properties and the condensate fraction are
      calculated and we also determine the critical temperature for the superfluid
      normal phase transition in this regime. The thermodynamic behavior appears as a
      rather surprising and unexpected melange of fermionic and bosonic features. The
      thermal response of a spin 1/2 fermion at the BCS-BEC crossover should be
      classified as that of a new type of superfluid.

PMID- 16606248
TI  - Quantum key distribution with higher-order alphabets using spatially encoded
      qudits.
AB  - We present a proof of principle demonstration of a quantum key distribution
      scheme in higher-order -dimensional alphabets using spatial degrees of freedom of
      photons. Our implementation allows for the transmission of 4.56 bits per sifted
      photon, while providing improved security: an intercept-resend attack on all
      photons would induce an average error rate of 0.47. Using our system, it should
      be possible to send more than a byte of information per sifted photon.

PMID- 16606249
TI  - Equilibrium free energies from nonequilibrium metadynamics.
AB  - In this Letter we propose a new formalism to map history-dependent metadynamics
      in a Markovian process. We apply this formalism to model Langevin dynamics and
      determine the equilibrium distribution of a collection of simulations. We
      demonstrate that the reconstructed free energy is an unbiased estimate of the
      underlying free energy and analytically derive an expression for the error. The
      present results can be applied to other history-dependent stochastic processes,
      such as Wang-Landau sampling.

PMID- 16606250
TI  - New critical frontiers for the potts and percolation models.
AB  - We obtain the critical threshold for a host of Potts and percolation models on
      lattices having a structure which permits a duality consideration. The
      consideration generalizes the recently obtained thresholds of Scullard and Ziff
      for bond and site percolation on the martini and related lattices to the Potts
      model and to other lattices.

PMID- 16606251
TI  - Supernova neutrino nucleosynthesis of light elements with neutrino oscillations.
AB  - Light element synthesis in supernovae through neutrino-nucleus interactions,
      i.e., the v process, is affected by neutrino oscillations in the supernova
      environment. There is a resonance of 13-mixing in the O/C layer, which increases
      the rates of charged-current -process reactions in the outer He-rich layer. The
      yields of 7Li and 11B increase by about a factor of 1.9 and 1.3, respectively,
      for a normal mass hierarchy and an adiabatic 13-mixing resonance, compared to
      those without neutrino oscillations. In the case of an inverted mass hierarchy
      and a nonadiabatic 13-mixing resonance, the increase in the 7Li and 11B yields is
      much smaller. Observations of the 7Li/11B ratio in stars showing signs of
      supernova enrichment could thus provide a unique test of neutrino oscillations
      and constrain their parameters and the mass hierarchy.

PMID- 16606252
TI  - Relic keV sterile neutrinos and reionization.
AB  - A sterile neutrino with a mass of several keV can account for cosmological dark
      matter, as well as explain the observed velocities of pulsars. We show that x
      rays produced by the decays of these relic sterile neutrinos can boost the
      production of molecular hydrogen, which can speed up the cooling of gas and the
      early star formation, which can, in turn, lead to a reionization of the Universe
      at a high enough redshift to be consistent with the Wilkinson Microwave
      Anisotropy Probe results.

PMID- 16606253
TI  - Flavor- and CP-violating physics from new supersymmetric thresholds.
AB  - Treating the minimal supersymmetric standard model as an effective theory, we
      study the implications of having dimension-five operators in the superpotential
      for flavor- and CP-violating processes, exploiting the linear decoupling of
      observable effects with respect to the new threshold scale c. We show that the
      assumption of weak-scale supersymmetry, when combined with the stringent limits
      on electric dipole moments and lepton-flavor-violating processes, provides
      sensitivity to Lambda as high as 10(7)-10(9) GeV (and up to 10(17) GeV through
      the theta term), while the next generation of experiments could directly probe
      the high-energy scales suggested by neutrino physics.

PMID- 16606254
TI  - Next-to-leading-order QCD correction to e(+)e(-)-->J/psi+eta(c) at sqrt[s]=10.6
      GeV.
AB  - One of the most challenging open problems in heavy quarkonium physics is the
      double charm production in e+e- annihilation at B factories. The measured cross
      section of e+e- --> J/psi + eta(c) is much larger than leading order (LO)
      theoretical predictions. With the nonrelativistic QCD factorization formalism, we
      calculate the next-to-leading order (NLO) QCD correction to this process. Taking
      all one loop self-energy, triangle, box, and pentagon diagrams into account, and
      factoring the Coulomb-singular term into the cc bound state wave function, we get
      an ultraviolet and infrared finite correction to the cross section of e+e- -->
      J/psi + eta(c) at sqrt[s] = 10:6 GeV. We find that the NLO QCD correction can
      substantially enhance the cross section with a K factor (the ratio of NLO to LO)
      of about 1.8-2.1; hence, it greatly reduces the large discrepancy between theory
      and experiment.

PMID- 16606257
TI  - Experimental signature of medium modifications for rho and omega mesons in the 12
      GeV p+A reactions.
AB  - The invariant mass spectra of e+e- pairs produced in 12 GeV proton-induced
      nuclear reactions are measured at the KEK Proton Synchrotron. On the low-mass
      side of the meson peak, a significant enhancement over the known hadronic sources
      has been observed. The mass spectra, including the excess, are well reproduced by
      a model that takes into account the density dependence of the vector meson mass
      modification, as theoretically predicted.

PMID- 16606255
TI  - Measurement of sigma(e+e- -->psi(3770)-->hadrons) at Ec.m.=3773 MeV.
AB  - We measure the cross section for e+e- -->psi(3770) -->hadrons at Ec.m.=3773 MeV
      to be (6.38+/-0.08(+0.41)(-0.30) nb using the CLEO detector at the CESR e+e-
      collider. The difference between this and the e+e- -->psi(3770) -->DD cross
      section at the same energy is found to be (-0.01+/-0.08(+0.41)(-0.30) nb. With
      the observed total cross section, we extract Gamma(ee)(psi(3770))=(0.204+/
      0.003(+0.041)(-0.027) keV. Uncertainties shown are statistical and systematic,
      respectively.

PMID- 16606258
TI  - 58Ni: an unpaired band crossing at new heights of angular momentum for rotating
      nuclei.
AB  - High-spin states in 58Ni have been investigated by means of the fusion
      evaporation reaction 28Si(32S, 2p)58Ni at 130 MeV beam energy. Discrete-energy
      levels are observed in 58Ni at record-breaking 42 MeV excitation energy and
      angular momenta in excess of 30h. The states form regular rotational bands with
      unprecedented high rotational frequencies. A comparison with configuration
      dependent cranked Nilsson-Strutinsky calculations reveals an exceptional two-band
      crossing scenario, the interaction strength of which is strongly shape dependent.

PMID- 16606259
TI  - Detection of the 1pe series of doubly excited helium states below N=2 via the
      stark effect.
AB  - The Stark effect on the doubly excited states of helium below the N=2 threshold
      has been studied by vacuum ultraviolet fluorescence yield spectroscopy. Two new
      series of states are observed at moderate fields (<10 kV/cm), and assigned to the
      previously unobserved even 1pe series, and a group of 1De series. The 1Se states
      are observed indirectly via their mixing with nearby 1 po states. The
      observations at moderate field contradict theoretical predictions that field
      strengths about an order of magnitude greater are necessary to observe the Stark
      effect on He doubly excited states at low quantum numbers.

PMID- 16606256
TI  - Dielectron widths of the Gamma(1S,2S,3S) resonances.
AB  - We determine the dielectron widths of the Gamma(1S), Gamma(2S), and Gamma(3S)
      resonances with better than 2% precision by integrating the cross section of e+e-
      -->Gamma over the e+e- center-of-mass energy. Using e+e- energy scans of the
      Gamma resonances at the Cornell Electron Storage Ring and measuring Gamma
      production with the CLEO detector, we find dielectron widths of 1.252+/
      0.004(sigma(stat))+/-0.019(sigma(syst)) keV, 0.581+/-0.004+/-0.009 keV, and
      0.413+/-0.004+/-0.006 keV for the Gamma(1S), Gamma(2S), and Gamma(3S),
      respectively.

PMID- 16606260
TI  - Real-time observation of phase-controlled molecular wave-packet interference.
AB  - The quantum interference of two molecular wave packets has been precisely
      controlled in the B electronic state of the I2 molecule by using a pair of fs
      laser pulses whose relative phase is locked within the attosecond time scale and
      its real-time evolution has been observed by another fs laser pulse. It is
      clearly observed that the temporal evolution changes drastically as a function of
      the relative phase between the locked pulses, allowing us to read both amplitude
      and phase information stored in the wave functions of the molecular ensemble.

PMID- 16606261
TI  - State to state to state dynamics of the D+H2 -->HD+H reaction: control of
      transition-state pathways via reagent orientation.
AB  - The influence of reagent rotation on the dynamics of the D+H2 -->HD+H reaction is
      studied. The state-resolved differential cross section is measured using the
      Rydberg-atom scheme in a crossed beam experiment. It is found that the H2
      rotation has a strong influence on the results. This effect was traced to the
      selection of the quantum bottleneck states through reagent orientation, thus
      suggesting a novel strategy to control the transition-state pathways in direct
      chemical reactions.

PMID- 16606262
TI  - Effect of superradiance on transport of diffusing photons in cold atomic gases.
AB  - We show that in atomic gases cooperative effects like superradiance and
      subradiance lead to a potential between two atoms that decays like 1/r. In the
      case of superradiance, this potential is attractive for close enough atoms and
      can be interpreted as a coherent mesoscopic effect. The contribution of
      superradiant pairs to multiple scattering properties of a dilute gas, such as
      photon elastic mean free path and group velocity, is significantly different from
      that of independent atoms. We discuss the conditions under which these effects
      may be observed and compare our results to recent experiments on photon transport
      in cold atomic gases.

PMID- 16606263
TI  - Acoustically induced transparency in optically dense resonance medium.
AB  - It is shown that mechanical vibration (acoustical oscillation) of a solid medium
      along the propagation of multifrequency laser radiation enables one to control
      the resonant absorption. There exists an optimal spectral structure of the
      incident field dependent on vibration amplitude as well as the number and
      intensity of the frequency components that provides the full resonant
      transparency. A mechanism of the transparency is discussed. Transparency of this
      kind is shown to appear also via adiabatic modulation of the atomic transition
      frequency by an external microwave field.

PMID- 16606264
TI  - Observation of sub-poisson photon statistics in the cavity-QED microlaser.
AB  - We have measured the second-order correlation function of the cavity-QED
      microlaser output and observed a transition from photon bunching to antibunching
      with increasing average number of intracavity atoms. The observed correlation
      times and the transition from super- to sub-Poisson photon statistics can be well
      described by gain-loss feedback or enhanced-reduced restoring action against
      fluctuations in photon number in the context of a quantum microlaser theory and a
      photon rate equation picture. However, the theory predicts a degree of
      antibunching several times larger than that observed, which may indicate the
      inadequacy of its treatment of atomic velocity distributions.

PMID- 16606265
TI  - Quantum telecommunication based on atomic cascade transitions.
AB  - A quantum repeater at telecommunications wavelengths with long-lived atomic
      memory is proposed, and its critical elements are experimentally demonstrated
      using a cold atomic ensemble. Via atomic cascade emission, an entangled pair of
      1.53 microm and 780 nm photons is generated. The former is ideal for long
      distance quantum communication, and the latter is naturally suited for mapping to
      a long-lived atomic memory. Together with our previous demonstration of photonic
      to-atomic qubit conversion, both of the essential elements for the proposed
      telecommunications quantum repeater have now been realized.

PMID- 16606266
TI  - Nonadiabatic dynamics of the electromagnetic field and charge carriers in high-Q
      photonic crystal resonators.
AB  - We address, both experimentally and theoretically, phase and amplitude dynamics
      of the electromagnetic field in a two-dimensional photonic crystal when
      femtosecond pulses are injected. We demonstrate that the usual adiabatic
      approximation underlying the dynamics of field and carriers in a semiconductor
      resonator is no longer valid, since in general the photon lifetime cannot be
      neglected with respect to the carrier recombination lifetime. Parameter regions
      where adiabaticity is broken are shown, and the ubiquity of the observed
      dynamical scenario in the new generation of active photonic microresonators is
      predicted.

PMID- 16606267
TI  - Pattern stabilization through parameter alternation in a nonlinear optical
      system.
AB  - We report the first experimental realization of pattern formation in a spatially
      extended nonlinear system when the system is alternated between two states,
      neither of which exhibits patterning. Dynamical equations modeling the system are
      used for both numerical simulations and a weakly nonlinear analysis of the
      patterned states. The simulations show excellent agreement with the experiment.
      The nonlinear analysis provides an explanation of the patterning under
      alternation and accurately predicts both the observed dependence of the
      patterning on the frequency of alternation and the measured spatial frequencies
      of the patterns.

PMID- 16606268
TI  - Decay of turbulence in pipe flow.
AB  - A novel experiment has been devised which provides direct evidence for critical
      point behavior in the longstanding problem of the transition to turbulence in a
      pipe. The novelty lies in the quenching of turbulence by reducing the Reynolds
      number and observing the decay of disordered motion. Divergence of the time
      scales implies underlying deterministic dynamics which are analogous to those
      found in boundary crises in dynamical systems. A modulated wave packet emerges
      from the long term transients and this coherent state provides evidence for
      connections with recent theoretical developments.

PMID- 16606269
TI  - Tomography of injection and acceleration of monoenergetic electrons in a laser
      wakefield accelerator.
AB  - A tomographic diagnosis method was developed to systematically resolve the
      injection and acceleration processes of a monoenergetic electron beam in a laser
      wakefield accelerator. It was found that all the monoenergetic electrons are
      injected at the same location in the plasma column and accelerated from 5 to 55
      MeV energy in 200 microm distance. This is a direct measurement of the real
      acceleration gradient in a laser-wakefield accelerator, and the experimental data
      are consistent with the model of transverse wave breaking and beam loading for
      monoenergetic electron injection.

PMID- 16606270
TI  - Probing internal transport barriers with heat pulses in JET.
AB  - The first electron temperature modulation experiments in plasmas characterized by
      strong and long-lasting electron and ion internal transport barriers (ITB) have
      been performed in JET using ion cyclotron resonance heating in mode conversion
      scheme. The ITB is shown to be a well localized narrow layer with low heat
      diffusivity, characterized by subcritical transport and loss of stiffness. In
      addition, results from cold pulse propagation experiments suggest a second order
      transition process for ITB formation.

PMID- 16606271
TI  - Direction of impurity pinch and auxiliary heating in tokamak plasmas.
AB  - A mechanism of particle pinch for trace impurities in tokamak plasmas, arising
      from the effect of parallel velocity fluctuations in the presence of a turbulent
      electrostatic potential, is identified analytically by means of a reduced fluid
      model and verified numerically with a gyrokinetic code for the first time. The
      direction of such a pinch reverses as a function of the direction of rotation of
      the turbulence in agreement with the impurity pinch reversal observed in some
      experiments when moving from dominant auxiliary ion heating to dominant auxiliary
      electron heating.

PMID- 16606272
TI  - Whistler modes with wave magnetic fields exceeding the ambient field.
AB  - Whistler-mode wave packets with fields exceeding the ambient dc magnetic field
      have been excited in a large, high electron-beta plasma. The waves are induced
      with a loop antenna with dipole moment either along or opposite to the dc field.
      In the latter case the excited wave packets have the topology of a spheromak but
      are propagating in the whistler mode along and opposite to the dc magnetic field.
      Field-reversed configurations with net zero helicity have also been produced. The
      electron magnetohydrodynamics fields are force free, have wave energy density
      exceeding the particle energy density, and propagate stably at subelectron
      thermal velocities through a nearly uniform stationary ion density background.

PMID- 16606273
TI  - Measurement of a long electronic spin relaxation time of cesium atoms in
      superfluid helium.
AB  - The longitudinal electronic spin relaxation time of Cs atoms optically polarized
      in superfluid helium (He II, 1.5 K) has been measured with special care to cope
      with a serious decrease in the number of Cs atoms in the observation region. This
      decrease, mainly caused by helium convection in introducing the atoms into He II
      by laser sputtering, was significantly reduced using a new atom implantation
      method. Combined with a careful correction for the number of atoms, we have
      determined the relaxation time to be 2.24(19) s or longer, roughly twice as long
      as that in solid He.

PMID- 16606274
TI  - Experimental realization of the fuse model of crack formation.
AB  - In this work, we present an experimental investigation of the fuse model. Our
      main goal was to study the influence of the disorder on the fracture process. The
      experimental apparatus used consisted of an L x L square lattice with fuses
      placed on each bond of the lattice. Two types of materials were used as fuses:
      copper and steel wool wires. The lattice composed only of copper wires varied
      from a weakly disordered system to a strongly disordered one. The lattice formed
      only by steel wool wires corresponded to a strongly disordered one. The
      experimental procedure consisted of applying a potential difference V to the
      lattice and measuring the respective current I. The characteristic function I(V)
      obtained was investigated in order to find the scaling law dependence of the
      voltage and the current on the system size L when the disorder was changed. Our
      results show that the scaling laws are only verified for the disordered regime.

PMID- 16606275
TI  - Determining the structure of phosphorus in phase IV.
AB  - We explore the unknown structure of phosphorus in phase IV (P-IV phase) based on
      first-principles calculations using the metadynamics simulation method. Starting
      from the simple cubic structure, we find a new modulated structure of the
      monoclinic lattice. The modulation is crucial to the stability of the structure.
      Through refining the structure further by changing the modulation period, we find
      the structure whose x-ray powder diffraction pattern is in best agreement with
      the experimental pattern. We expect that the modulation period of the structure
      in the P-IV phase is very close to that found in this study and probably
      incommensurate.

PMID- 16606276
TI  - Mesoscale theory of grains and cells: crystal plasticity and coarsening.
AB  - Crystals with spatial variations in their axes naturally evolve into cells or
      grains separated by sharp walls. At high temperatures, polycrystalline grains
      form from the melt and coarsen with time: the dislocations can both climb and
      glide. At low temperatures under shear the dislocations (which allow only glide)
      form into cell structures. We present here a mesoscale theory of dislocation
      motion. It provides a quantitative description of deformation and rotation,
      grounded in a microscopic order parameter field exhibiting the topologically
      conserved quantities. The topological current of the Nye dislocation density
      tensor is derived from a microscopic theory of glide driven by Peach-Koehler
      forces between dislocations using a simple closure approximation. The resulting
      theory is shown to form sharp dislocation walls in finite time, both with and
      without dislocation climb.

PMID- 16606277
TI  - Salt permeation and exclusion in hydroxylated and functionalized silica pores.
AB  - We use combined ab initio molecular dynamics (AIMD), grand canonical Monte Carlo,
      and molecular dynamics techniques to study the effect of pore surface chemistry
      and confinement on the permeation of salt into silica nanopore arrays filled with
      water. AIMD shows that 11.6 A diameter hydroxylated silica pores are relatively
      stable in water, whereas amine groups on functionalized pore surfaces abstract
      silanol protons, turning into NH3+. Free energy calculations using an ab initio
      parametrized force field show that the hydroxylated pores strongly attract Na+
      and repel Cl- ions. Pores lined with NH3+ have the reverse surface charge
      polarity. Finally, studies of ions in carbon nanotubes suggest that hydration of
      Cl- is more strongly frustrated by pure confinement effects than Na+.

PMID- 16606278
TI  - Multiparadigm modeling of dynamical crack propagation in silicon using a reactive
      force field.
AB  - We report a study of dynamic cracking in a silicon single crystal in which the
      ReaxFF reactive force field is used for several thousand atoms near the crack
      tip, while more than 100,000 atoms are described with a nonreactive force field.
      ReaxFF is completely derived from quantum mechanical calculations of simple
      silicon systems without any empirical parameters. Our results reproduce
      experimental observations of fracture in silicon including changes in crack
      dynamics for different crack orientations.

PMID- 16606279
TI  - Thermodynamic glass transition in finite dimensions.
AB  - Using an effective potential method, a replica formulism is set up for describing
      supercooled liquids near their glass transition. The resulting potential is
      equivalent to that for an Ising spin glass in a magnetic field. Results taken
      from the droplet picture of spin glasses are then used to provide an explanation
      of the main features of fragile glasses.

PMID- 16606280
TI  - Inelastic spectroscopy identification of STM-induced benzene dehydrogenation.
AB  - Inelastic electron tunneling spectroscopy (IETS) performed with the scanning
      tunneling microscope (STM) has been deemed as the ultimate tool for identifying
      chemicals on the atomic scale. However, IETS-based chemical analysis is error
      prone due to the numerous degrees of freedom of chemisorbed molecular systems.
      First-principles simulations of IETS are presented that, by quantitative
      comparison with the experimental spectra, permit one to determine the final
      products of an STM-induced reaction on chemisorbed benzene. Our simulations
      reveal that IETS possesses an enhanced sensitivity to atomic structure as
      compared to topographic imaging due to both its energy and space resolution.

PMID- 16606281
TI  - Multidimensional effects on dissociation of N2 on Ru(0001).
AB  - The applicability of the Born-Oppenheimer approximation to molecule-metal surface
      reactions is presently a topic of intense debate. We have performed classical
      trajectory calculations on a prototype activated dissociation reaction, of N2 on
      Ru(0001), using a potential energy surface based on density functional theory.
      The computed reaction probabilities are in good agreement with molecular beam
      experiments. Comparison to previous calculations shows that the rotation of N2
      and its motion along the surface affect the reactivity of N2 much more than
      nonadiabatic effects.

PMID- 16606282
TI  - Diffusion dynamics during the nucleation and growth of Ge/Si nanostructures on
      Si(111).
AB  - We report a low energy electron microscopy study of the relation between self
      organized Ge/Si(111)nanostructures and their local environment. By comparison
      with Monte Carlo simulations, three-dimensional islands are shown to display a
      substantial tendency towards self-ordering. This tendency may result from the
      diffusive nature of the nucleation processes. The size of individual
      nanostructures does not significantly correlate with the distance between
      neighboring islands. Thus energetic factors are thought to govern the competition
      among coexisting nanostructures to capture the deposited mass.

PMID- 16606283
TI  - Magic structures and quantum conductance of silver nanowires.
AB  - We investigate the pathway of thinning process for transient [110] nanowires
      (NWs) of Ag. The result is in good agreement with experimental observations. An
      unambiguous identification of the structure of a NW requires at least two views
      along different directions. In the cases where two views of different NW
      structures are practically the same for very thin NWs which pose experimental
      difficulty due to small signal-to-noise ratio, our theoretical analysis helps
      distinguish these structures. On the basis of conductance (G) calculations vis-a
      vis the structure of transient NWs, the puzzling experimental observation of
      fractionally quantized G values is explained by considering the existence of
      mixed structures for thin wires.

PMID- 16606284
TI  - Diameter-independent kinetics in the vapor-liquid-solid growth of Si nanowires.
AB  - We examine individual Si nanowires grown by the vapor-liquid-solid mechanism,
      using real-time in situ ultra high vacuum transmission electron microscopy. By
      directly observing Au-catalyzed growth of Si wires from disilane, we show that
      the growth rate is independent of wire diameter, contrary to the expected
      behavior. Our measurements show that the unique rate-limiting step here is the
      irreversible, kinetically limited, dissociative adsorption of disilane directly
      on the catalyst surface. We also identify a novel dependence of growth rate on
      wire taper.

PMID- 16606285
TI  - Statistical estimation of atomic positions from exit wave reconstruction with a
      precision in the picometer range.
AB  - The local structure of Bi4W2/3Mn1/3O8Cl is determined using quantitative
      transmission electron microscopy. The electron exit wave, which is closely
      related to the projected crystal potential, is reconstructed and used as a
      starting point for statistical parameter estimation. This method allows us to
      refine all atomic positions on a local scale, including those of the light atoms,
      with a precision in the picometer range. Using this method one is no longer
      restricted to the information limit of the electron microscope. Our results are
      in good agreement with x-ray powder diffraction data demonstrating the
      reliability of the method. Moreover, it will be shown that local effects can be
      interpreted using this approach.

PMID- 16606286
TI  - Observation of surface layering in a nonmetallic liquid.
AB  - Oscillatory density profiles (layers) have previously been observed at the free
      surfaces of liquid metals but not in other isotropic liquids. We have used x-ray
      reflectivity to study a molecular liquid, tetrakis(2-ethylhexoxy)silane. When
      cooled to T/Tc approximately 0.25 (well above the freezing point for this
      liquid), density oscillations appear at the surface. Lateral order within the
      layers is liquidlike. Our results confirm theoretical predictions that a surface
      layered state will appear even in dielectric liquids at sufficiently low
      temperatures, if not preempted by freezing.

PMID- 16606287
TI  - Charge-orbital ordering and Verwey transition in magnetite measured by resonant
      soft X-ray scattering.
AB  - We report experimental evidence for the charge-orbital ordering in magnetite
      below the Verwey transition temperature T(V). Measurements of O K-edge resonant x
      ray scattering on magnetite reveal that the O 2p states in the vicinity of the
      Fermi level exhibit a charge-orbital ordering along the c axis with a spatial
      periodicity of the doubled lattice parameter of the undistorted cubic phase. Such
      a charge-orbital ordering vanishes abruptly above T(V) and exhibits a thermal
      hysteresis, correlating closely with the Verwey transition in magnetite.

PMID- 16606288
TI  - In-chain tunneling through charge-density-wave nanoconstrictions and break
      junctions.
AB  - We have fabricated longitudinal nanoconstrictions in the charge-density wave
      conductor (CDW) NbSe3 using a focused ion beam and using a mechanically
      controlled break-junction technique. Conductance peaks are observed below the
      TP1=145 K and TP2=59 K CDW transitions, which correspond closely with previous
      values of the full CDW gaps 2Delta1 and 2Delta2 obtained from photoemission.
      These results can be explained by assuming CDW-CDW tunneling in the presence of
      an energy gap corrugation epsilon2 comparable to Delta2, which eliminates
      expected peaks at +/-|Delta1+Delta2|. The nanometer length scales our experiments
      imply indicate that an alternative explanation based on tunneling through back-to
      back CDW-normal-conductor junctions is unlikely.

PMID- 16606289
TI  - Charge and spin ordering in insulating Na0.5CoO2: effects of correlation and
      symmetry.
AB  - Ab initio band theory including correlations due to intra-atomic repulsion is
      applied to study charge disproportionation and charge and spin ordering in
      insulating Na0.5CoO2. Various ordering patterns (zigzag and two striped) for four
      Co supercells are analyzed before focusing on the observed "out-of-phase stripe"
      pattern of antiferromagnetic Co4+ spins along charge-ordered stripes. This
      pattern relieves frustration and shows distinct analogies with the cuprate
      layers: a bipartite lattice of antialigned spins, with axes at 90degrees angles.
      Substantial distinctions with cuprates are also discussed, including the tiny gap
      of a new variant of "charge-transfer" type within the Co 3d system.

PMID- 16606290
TI  - Velocity of domain-wall motion induced by electrical current in the ferromagnetic
      semiconductor (Ga,Mn)As.
AB  - Current-induced domain-wall motion with velocity spanning over 5 orders of
      magnitude up to 22 m/s has been observed by the magneto-optical Kerr effect in
      (Ga,Mn)As with perpendicular magnetic anisotropy. The data are employed to verify
      theories of spin transfer by the Slonczewski-like mechanism as well as by the
      torque resulting from spin-flip transitions in the domain-wall region. Evidence
      for domain-wall creep at low currents is found.

PMID- 16606291
TI  - Domain-wall resistance in ferromagnetic (Ga,Mn)As.
AB  - A series of microstructures designed to pin domain walls (DWs) in (Ga,Mn)As with
      perpendicular magnetic anisotropy has been employed to determine extrinsic and
      intrinsic contributions to DW resistance. The former is explained quantitatively
      as resulting from a polarity change in the Hall electric field at DW. The latter
      is 1 order of magnitude greater than a term brought about by anisotropic
      magnetoresistance and is shown to be consistent with disorder-induced mistracking
      of the carrier spins subject to spatially varying magnetization.

PMID- 16606292
TI  - Spin relaxation by transient monopolar and bipolar optical orientation.
AB  - We have used two-color time-resolved spectroscopy to measure the relaxation of
      electron spin polarizations in a bulk semiconductor. The circularly polarized
      pump beam induces a polarization either by direct excitation from the valence
      band, or by free-carrier (Drude) absorption when tuned to an energy below the
      band gap. We find that the spin relaxation time, measured with picosecond time
      resolution by resonant induced Faraday rotation in both cases, increases in the
      presence of photogenerated holes. In the case of the material chosen, n-InSb, the
      increase was from 14 to 38 ps.

PMID- 16606293
TI  - Quantum tunneling detection of two-photon and two-electron processes.
AB  - We analyze the operation of a quantum tunneling detector coupled to a coherent
      conductor. We demonstrate that, in a certain energy range, the output of the
      detector is determined by two-photon processes, two-interacting-electron
      processes, and the interference of the two. We show how the individual
      contributions of these processes can be resolved in experiments.

PMID- 16606294
TI  - Quantum control of donor electrons at the Si-SiO2 interface.
AB  - Prospects for the quantum control of electrons in the silicon quantum computer
      architecture are considered theoretically. In particular, we investigate the
      feasibility of shuttling donor-bound electrons between the impurity in the bulk
      and the Si-SiO2 interface by tuning an external electric field. We calculate the
      shuttling time to range from subpicoseconds to nanoseconds depending on the
      distance (approximately 10-50 nm) of the donor from the interface. Our results
      establish that quantum control in such nanostructure architectures could, in
      principle, be achieved.

PMID- 16606295
TI  - Rectification mechanism in diblock oligomer molecular diodes.
AB  - We investigated a mechanism of rectification in diblock oligomer diode molecules
      that have recently been synthesized and showed a pronounced asymmetry in the
      measured I-V spectrum. The observed rectification effect is due to the resonant
      nature of electron transfer in the system and the localization properties of
      bound state wave functions of resonant states of the tunneling electron
      interacting with an asymmetric molecule in an electric field. The asymmetry of
      the tunneling wave function is enhanced or weakened depending on the polarity of
      the applied bias. The conceptually new theoretical approach, the Green's function
      theory of sub-barrier scattering, is able to provide a physically transparent
      explanation of this rectification effect based on the concept of the bound state
      spectrum of a tunneling electron. The theory predicts the characteristic features
      of the I-V spectrum in qualitative agreement with experiment.

PMID- 16606296
TI  - Effective Kondo model for a trimer on a metallic surface.
AB  - I consider a Hubbard-Anderson model which describes localized orbitals in three
      different atoms hybridized both among themselves and with a continuum of extended
      states. Using a generalized Schrieffer-Wolf transformation, I derive an effective
      Kondo model for the interaction between the doublet ground state of the isolated
      trimer and the extended states. For an isoceles trimer with distances a, l, l
      between the atoms, the Kondo temperature is very small for l<a and has a maximum
      for finite l>a when a is small. The results agree with experiments for a Cr
      trimer on Au(111).

PMID- 16606297
TI  - Raising Bi-O bands above the Fermi energy level of hole-doped Bi2Sr2CaCu2O8+delta
      and other cuprate superconductors.
AB  - The Fermi surface (FS) of Bi2Sr2CaCu2O8+delta (Bi2212) predicted by band theory
      displays Bi-related pockets around the (pi, 0) point, which have never been
      observed experimentally. We show that when the effects of hole doping either by
      substituting Pb for Bi or by adding excess O in Bi2212 are included, the Bi-O
      bands are lifted above the Fermi energy (E(F)) and the resulting first-principles
      FS is in remarkable accord with measurements. With decreasing hole doping the Bi
      O bands drop below and the system self-dopes below a critical hole concentration.
      Computations on other Bi- as well as Tl- and Hg-based compounds indicate that
      lifting of the cation-derived band with hole doping is a general property of the
      electronic structures of the cuprates.

PMID- 16606298
TI  - Effects of edge boundaries on Josephson vortices in finite-size layered high-Tc
      superconductors.
AB  - In order to systematically explain the in-plane size effects for the periodical
      dependence of the Josephson-vortex-flow resistance on the magnetic field, we
      numerically explore static lattice structures of Josephson vortices in layered
      high-Tc superconductors with finite in-plane sizes from sub-microm to more than
      10 microm by simulating slow quenching processes from high temperature under the
      magnetic field. The numerical results reveal that in sub-microm size the
      rectangular lattice is a widely spread major structure in H-T diagram and the
      triangular lattice is a minor one which emerges only around the specific magnetic
      field supplying n(phi)0 per one junction area. These results suggest that sub
      microm size layered high-Tc superconductors are promising for future device
      applications.

PMID- 16606299
TI  - Hysteresis and noise from electronic nematicity in high-temperature
      superconductors.
AB  - An electron nematic is a translationally invariant state which spontaneously
      breaks the discrete rotational symmetry of a host crystal. In a clean square
      lattice, the electron nematic has two preferred orientations, while dopant
      disorder favors one or the other orientations locally. In this way, the electron
      nematic in a host crystal maps to the random field Ising model. Since the
      electron nematic has anisotropic conductivity, we associate each Ising
      configuration with a resistor network and use what is known about the random
      field Ising model to predict new ways to test for local electronic nematic order
      (nematicity) using noise and hysteresis. In particular, we have uncovered a
      remarkably robust linear relation between the orientational order and the
      resistance anisotropy which holds over a wide range of circumstances.

PMID- 16606300
TI  - Andreev states near short-ranged pairing potential impurities.
AB  - We study Andreev states near atomic scale modulations in the pairing potential in
      both s- and d-wave superconductors with short coherence lengths. For a moderate
      reduction of the local gap, the states exist only close to the gap edge. If one
      allows for local sign changes of the order parameter, however, resonances can
      occur at energies close to the Fermi level. The local density of states (LDOS)
      around such pairing potential defects strongly resembles the patterns observed by
      tunneling measurements around Zn impurities in Bi2Sr2CaCu2O8+x (BSCCO). We
      discuss how this phase impurity model of the Zn LDOS pattern can be distinguished
      from other proposals experimentally.

PMID- 16606301
TI  - Relaxation and persistent oscillations of the order parameter in fermionic
      condensates.
AB  - We determine the limiting dynamics of a fermionic condensate following a sudden
      perturbation for various initial conditions. Possible initial states of the
      condensate fall into two classes. In the first case, the order parameter
      asymptotes to a constant value. The approach to a constant is oscillatory with an
      inverse square root decay. This happens, e.g., when the strength of pairing is
      abruptly changed while the system is in the paired ground state and more
      generally for any nonequilibrium state that is in the same class as the ground
      state. In the second case, the order parameter exhibits persistent oscillations
      with several frequencies. This is realized for nonequilibrium states that belong
      to the same class as excited stationary states.

PMID- 16606302
TI  - Tunneling spectroscopy and vortex imaging in boron-doped diamond.
AB  - We present the first scanning tunneling spectroscopy study of single-crystalline
      boron-doped diamond. The measurements were performed below 100 mK with a low
      temperature scanning tunneling microscope. The tunneling density of states
      displays a clear superconducting gap. The temperature evolution of the order
      parameter follows the weak-coupling BCS law with Delta(0)/kBTc approximately
      1.74. Vortex imaging at low magnetic field also reveals localized states inside
      the vortex core that are unexpected for such a dirty superconductor.

PMID- 16606303
TI  - Anomalous Josephson effect in p-wave dirty junctions.
AB  - The Josephson effect in p-wave superconductor/diffusive normal metal/p-wave
      superconductor junctions is studied theoretically. Amplitudes of Josephson
      currents are several orders of magnitude larger than those in s-wave junctions.
      Current-phase (J-phi) relations in low temperatures are close to those in
      ballistic junctions such as J proportional to sin(phi/2) and J proportional to
      phi even in the presence of random impurity potentials. A cooperative effect
      between the midgap Andreev resonant states and the proximity effect causes such
      anomalous properties and is a character of the spin-triplet superconductor
      junctions.

PMID- 16606304
TI  - Nearly free electrons in the layered oxide superconductor Ag5Pb2O6.
AB  - We present first measurements of quantum oscillations in the layered oxide
      superconductor Ag5Pb2O6. From a detailed angular and temperature dependent study
      of the de Haas-van Alphen effect we determine the electronic structure and
      demonstrate that the electron masses are very light, m* approximately 1.2me. The
      Fermi surface we observe is essentially that expected of nearly free electrons-
      establishing Ag5Pb2O6 as the first known example of a monovalent, nearly free
      electron superconductor at ambient pressure.

PMID- 16606305
TI  - Non-Gaussian low-frequency noise as a source of qubit decoherence.
AB  - We study decoherence in a qubit with the distance between the two levels affected
      by random flips of bistable fluctuators. For the case of a single fluctuator we
      evaluate explicitly an exact expression for the phase-memory decay in the echo
      experiment with a resonant ac excitation. The echo signal as a function of time
      shows a sequence of plateaus. The position and the height of the plateaus can be
      used to extract the fluctuator switching rate gamma and its coupling strength v.
      At small times the logarithm of the echo signal is proportional to t3. The
      plateaus disappear when the decoherence is induced by many fluctuators. In this
      case the echo signal depends on the distribution of the fluctuators parameters.
      According to our analysis, the results significantly deviate from those obtained
      in the Gaussian model as soon as v greater than or approximately equal gamma.

PMID- 16606306
TI  - Low temperature charge and orbital textures in La0.875Sr0.125MnO3.
AB  - By using nuclear magnetic resonance techniques we show that for T<30 K the
      La0.875Sr0.125MnO3 compound displays a nonuniform charge distribution, comprised
      of two interconnected Mn ion subsystems with different spin, orbital, and charge
      couplings. The NMR results agree very well with the two spin wave stiffness
      constants observed at small q values in the spin wave dispersion curves [Phys.
      Rev. B 67, 214430 (2003)]. This picture is probably related to a yet undetermined
      charge and orbital superstructure occurring in the ferromagnetic insulating state
      of the La0.875Sr0.125MnO3 compound.

PMID- 16606307
TI  - Collinear to spiral spin transformation without changing the modulation
      wavelength upon ferroelectric transition in Tb1-xDyxMnO3.
AB  - Lattice modulation and magnetic structures in magnetoelectric compounds Tb1
      xDyxMnO3 have been studied around the ferroelectric (FE) Curie temperature TC by
      x-ray and neutron diffraction. Temperature-independent modulation vectors through
      TC are observed for the compounds with 0.50 <or=x<or=0.68. This indicates that
      ferroelectricity with a polarization (P) along the c axis in the RMnO3 series
      cannot be ascribed to such an incommensurate-commensurate transition of an
      antiferromagnetic order as was previously anticipated. A neutron diffraction
      study with x=0.59 shows that the FE transition is accompanied by the
      transformation of the Mn-spin alignment from sinusoidal (collinear)
      antiferromagnetism into a transverse-spiral structure. The observed spiral
      structure below TC is expected to produce P along the c axis with the "inverse"
      Dzialoshinski-Moriya interaction, which is consistent with observation.

PMID- 16606308
TI  - Electronic structure and bulk spin-valve behavior in Ca3Ru2O7.
AB  - Density functional calculations of the fermiology and magnetic properties of
      Ca3Ru2O7 reveal an unusual state: a bulk spin valve. The ground state consists of
      nearly half-metallic bilayers stacked antiferromagnetically with a weak coupling.
      Out of plane transport is very strongly suppressed by the antiferromagnetic
      alignment, which can be destroyed in favor of ferromagnetism at low energy cost.
      Furthermore, the spin transport in the ferromagnetic state is highly unusual;
      opposite sign spin polarizations are found for currents in plane and out of
      plane.

PMID- 16606309
TI  - Dynamics of magnetic domain wall motion after nucleation: dependence on the wall
      energy.
AB  - The dynamics of magnetic domain wall motion in the FeNi layer of a FeNi/Al2O3/Co
      trilayer has been investigated by a combination of x-ray magnetic circular
      dichroism, photoelectron emission microscopy, and a stroboscopic pump-probe
      technique. The nucleation of domains and subsequent expansion by domain wall
      motion in the FeNi layer during nanosecond-long magnetic field pulses was
      observed in the viscous regime up to the Walker limit field. We attribute an
      observed delay of domain expansion to the influence of the domain wall energy
      that acts against the domain expansion and that plays an important role when
      domains are small.

PMID- 16606310
TI  - Exactly solvable model for isospin S=3/2 fermionic atoms on an optical lattice.
AB  - We propose an exact solution of a model describing a low energy behavior of cold
      isospin S=3/2 fermionic atoms on a one-dimensional optical lattice. Depending on
      the band filling the effective field theory has a form of a deformed Gross-Neveu
      model with either O(7)x Z2 (half filling) or U(1) x O(5) x Z2 symmetry.

PMID- 16606311
TI  - Ground states and defect energies of the two-dimensional XY spin glass from a
      quasiexact algorithm.
AB  - We employ a novel algorithm using a quasiexact embedded-cluster matching
      technique as minimization method within a genetic algorithm to reliably obtain
      numerically exact ground states of the Edwards-Anderson XY spin-glass model with
      bimodal coupling distribution for square lattices of up to 28 x 28 spins.
      Contrary to previous conjectures, the ground state of each disorder replica is
      nondegenerate up to a global O(2) rotation. The scaling of spin and chiral defect
      energies induced by applying several different sets of boundary conditions
      exhibits strong crossover effects. This suggests that previous calculations have
      yielded results far from the asymptotic regime. The novel algorithm and the
      aspect-ratio scaling technique consistently give theta(s)=-0.308(30) and
      theta(c)=-0.114(16) for the spin and chiral stiffness exponents, respectively.

PMID- 16606312
TI  - Quantum effects in a half-polarized pyrochlore antiferromagnet.
AB  - We study quantum effects in a spin-3/2 antiferromagnet on the pyrochlore lattice
      in an external magnetic field, focusing on the vicinity of a plateau in the
      magnetization at half the saturation value, observed in CdCr2O4 and HgCr2O4. Our
      theory, based on quantum fluctuations, predicts the existence of a symmetry
      broken state on the plateau, even with only nearest-neighbor microscopic
      exchange. This symmetry-broken state consists of a particular arrangement of
      spins polarized parallel and antiparallel to the field in a 3:1 ratio on each
      tetrahedron. It quadruples the lattice unit cell, and reduces the space group
      from Fd3m to P4(3)32. We also predict that for fields just above the plateau, the
      low-temperature phase has transverse spin order, describable as a Bose-Einstein
      condensate of magnons. Other comparisons to and suggestions for experiments are
      discussed.

PMID- 16606313
TI  - Squeezing visible light waves into a 3-nm-thick and 55-nm-long plasmon cavity.
AB  - We demonstrate controlled squeezing of visible light waves into nanometer-sized
      optical cavities. The light is perpendicularly confined in a few-nanometer-thick
      SiO2 film sandwiched between Au claddings in the form of surface plasmon
      polaritons and exhibits Fabry-Perot resonances in a longitudinal direction. As
      the thickness of the dielectric core is reduced, the plasmon wavelength becomes
      shorter; then a smaller cavity is realized. A dispersion relation down to a
      surface plasmon wavelength of 51 nm for a red light, which is less than 8% of the
      free-space wavelength, was experimentally observed. Any obvious breakdowns of the
      macroscopic electromagnetics based on continuous dielectric media were not
      disclosed for 3-nm-thick cores.

PMID- 16606314
TI  - Non-Poissonian exciton populations in semiconductor nanocrystals via carrier
      multiplication.
AB  - We analyze distributions of exciton populations in PbSe nanocrystal (NC)
      ensembles as a function of excitation wavelength. For photon energies that result
      in carrier multiplication, these distributions are non-Poissonian and are
      characterized by two dominant exciton multiplicities that are determined by the
      ratio of photon energy to NC energy gap. For certain photon energies, we produce
      photoexcited NC ensembles with a nearly pure single multiplicity that can be
      tuned from 1 to 7. This result can find applications ranging from lasing and
      nonlinear optics to photovoltaics and photocatalysis.

PMID- 16606315
TI  - Ferroelectricity induced by acentric spin-density waves in YMn2O5.
AB  - The commensurate and incommensurate magnetic structures of the magnetoelectric
      system YMn2O5, as determined from neutron diffraction, were found to be spin
      density waves lacking a global center of symmetry. We propose a model, based on a
      simple magnetoelastic coupling to the lattice, which enables us to predict the
      polarization based entirely on the observed magnetic structure. Our data
      accurately reproduce the temperature dependence of the spontaneous polarization,
      particularly its sign reversal at the commensurate-incommensurate transition.

PMID- 16606316
TI  - Optical and resonant X-ray diffraction studies confirm a SmC*FI2-SmC* liquid
      crystal phase sequence reversal.
AB  - Employing both null transmission ellipsometry and resonant x-ray diffraction, we
      confirmed the SmC*FI2-SmC* phase sequence reversal in one liquid crystal compound
      and specially prepared binary mixtures. This phase sequence reversal was
      predicted by two recent theoretical advances. Moreover, the temperature range for
      the SmC*FI2 phase increases significantly in the mixture suggesting that such a
      phase sequence may exist in other compounds.

PMID- 16606317
TI  - Sheared force networks: anisotropies, yielding, and geometry.
AB  - A scenario for the yielding of granular matter is presented by considering the
      ensemble of force networks for a given contact network and applied shear stress
      tau. As tau is increased, the probability distribution of contact forces becomes
      highly anisotropic, the difference between average contact forces along minor and
      major axes grows, and the allowed networks span a shrinking subspace of all force
      networks. Eventually, contacts start to break, and at the maximal shear stress
      the packing becomes effectively isostatic. The size of the allowed subspace
      exhibits simple scaling properties, which lead to a prediction for the yield
      stress for packings of an arbitrary contact number.

PMID- 16606318
TI  - Phase diagram of a ternary mixture of cholesterol and saturated and unsaturated
      lipids calculated from a microscopic model.
AB  - We employ a molecular model to study a ternary mixture of saturated lipid, with
      tails of 16 carbons, a monounsaturated lipid with tails of 18 carbons, and
      cholesterol. The model, solved within mean-field theory, produces several forms
      of phase diagrams depending upon the relative strengths of interactions, but only
      one that shows the coexistence of two liquid phases observed in experiment. The
      lipids in the phase rich in cholesterol are more ordered than those in the other.
      The binary cholesterol, saturated lipid system also exhibits liquid, liquid
      coexistence.

PMID- 16606319
TI  - Physical nature of bacterial cytoplasm.
AB  - We track the motion of individual fluorescently labeled mRNA molecules inside
      live E. coli cells. We find that the motion is subdiffusive, with an exponent
      that is robust to physiological changes, including the disruption of cytoskeletal
      elements. By modifying the parameters of the RNA molecule and the bacterial cell,
      we are able to examine the possible mechanisms that can lead to this unique type
      of motion, especially the effect of macromolecular crowding. We also examine the
      implications of anomalous diffusion on the kinetics of bacterial gene regulation,
      in particular, how transcription factors find their DNA targets.

PMID- 16606321
TI  - Nonequilibrium ribbon model of twisted scroll waves.
AB  - We formulate a reduced model to analyze the motion of the core of a twisted
      scroll wave. The model is first shown to provide a simple description of the
      onset and nonlinear evolution of the helical state appearing in the sproing
      bifurcation of scroll waves. It then serves to examine the experimentally studied
      case of a medium with spatially varying excitability. The model shows the role of
      sproing in this more complex setting and highlights the differences between the
      convective and absolute sproing instabilities.

PMID- 16606320
TI  - Neuronal growth: a bistable stochastic process.
AB  - The fundamentally stochastic nature of neuronal growth has hardly been addressed
      in neuroscience. We report on the stochastic fluctuations of a neuronal growth
      cone's leading edge movement, the basic step in neuronal growth. Describing the
      edge movement as a stochastic bistable process leads to an isotropic noise
      parameter that is successfully used to test the model. An analysis of growth cone
      motility confirms the model, and predicts that linear changes of the bistable
      potential, as known from stochastic filtering, result in directed growth cone
      translocation.

PMID- 16606322
TI  - Adhesion-induced DNA naturation.
AB  - DNA adsorption and naturation is modeled via two interacting flexible
      homopolymers coupled to a solid surface. DNA denatures if the entropy gain for
      unbinding the two strands overcomes the loss of binding energy. When adsorbed to
      a surface, the entropy gain is smaller than in the bulk, leading to a stronger
      binding and, upon neglecting self-avoidance, absence of a denatured phase. Now
      consider conditions where the binding potentials are too weak for naturation, and
      the surface potential too weak to adsorb single strands. In a variational
      approach it is shown that their combined action may lead to a naturated adsorbed
      phase. Conditions for the absence of naturation and adsorption are derived too.
      The phase diagram is constructed qualitatively.

PMID- 16606323
TI  - Quasiperiodic events in an earthquake model.
AB  - We introduce a modification of the Olami-Feder-Christensen earthquake model
      [Phys. Rev. Lett. 68, 1244 (1992)10.1103/PhysRevLett.68.1244] in order to improve
      the resemblence with the Burridge-Knopoff mechanical model and with possible
      laboratory experiments. A constant and finite force continually drives the
      system, resulting in instantaneous relaxations. Dynamical disorder is added to
      the thresholds following a narrow distribution. We find quasiperiodic behavior in
      the avalanche time series with a period proportional to the degree of dissipation
      of the system. Periodicity is not as robust as criticality when the threshold
      force distribution widens, or when an increasing noise is introduced in the
      values of the dissipation.

PMID- 16606324
TI  - Controlled irradiative formation of penitentes.
AB  - Spike-shaped structures are produced by light-driven ablation in very different
      contexts. Penitentes 1-4 m high are common on Andean glaciers, where their
      formation changes glacier dynamics and hydrology. Laser ablation can produce
      cones 10-100 microm high with a variety of proposed applications in materials
      science. We report the first laboratory generation of centimeter-scale snow and
      ice penitentes. Systematically varying conditions allows identification of the
      parameters controlling the formation of ablation structures. We demonstrate that
      penitente initiation and coarsening require cold temperatures, so that ablation
      leads to sublimation. Once penitentes have formed, further growth of height can
      occur by melting. The penitentes initially appear as small structures (3 mm high)
      and grow by coarsening to 1-5 cm high. Our results are an important step towards
      understanding ablation morphologies.

PMID- 16606325
TI  - Dynamics of networking agents competing for high centrality and low degree.
AB  - We model a system of networking agents that seek to optimize their centrality in
      the network while keeping their cost, the number of connections they are
      participating in, low. Unlike other game-theory based models for network
      evolution, the success of the agents is related only to their position in the
      network. The agents use strategies based on local information to improve their
      chance of success. Both the evolution of strategies and network structure are
      investigated. We find a dramatic time evolution with cascades of strategy change
      accompanied by a change in network structure. On average the network self
      organizes to a state close to the transition between a fragmented state and a
      state with a giant component. Furthermore, with increasing system size both the
      average degree and the level of fragmentation decreases.

PMID- 16606326
TI  - Comment on "Superlubricity: a paradox about confined fluids resolved".

PMID- 16606328
TI  - Comment on "Berry phase correction to electron density of states in solids".

PMID- 16606330
TI  - Chronic oxidative stress and cancer: mechanisms, biomarkers and prevention.
      Proceedings of an international conference. October 23-26, 2005. Heidelberg,
      Germany.

PMID- 16606331
TI  - Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on
      alcohol and oxidative stress.
AB  - Hepatocellular cancer is the fifth most frequent cancer in men and the eighth in
      women worldwide. Established risk factors are chronic hepatitis B and C
      infection, chronic heavy alcohol consumption, obesity and type 2 diabetes,
      tobacco use, use of oral contraceptives, and aflatoxin-contaminated food. Almost
      90% of all hepatocellular carcinomas develop in cirrhotic livers. In Western
      countries, attributable risks are highest for cirrhosis due to chronic alcohol
      abuse and viral hepatitis B and C infection. Among those with alcoholic
      cirrhosis, the annual incidence of hepatocellular cancer is 1-2%. An important
      mechanism implicated in alcohol-related hepatocarcinogenesis is oxidative stress
      from alcohol metabolism, inflammation, and increased iron storage. Ethanol
      induced cytochrome P-450 2E1 produces various reactive oxygen species, leading to
      the formation of lipid peroxides such as 4-hydroxy-nonenal. Furthermore, alcohol
      impairs the antioxidant defense system, resulting in mitochondrial damage and
      apoptosis. Chronic alcohol exposure elicits hepatocyte hyperregeneration due to
      the activation of survival factors and interference with retinoid metabolism.
      Direct DNA damage results from acetaldehyde, which can bind to DNA, inhibit DNA
      repair systems, and lead to the formation of carcinogenic exocyclic DNA etheno
      adducts. Finally, chronic alcohol abuse interferes with methyl group transfer and
      may thereby alter gene expression.

PMID- 16606332
TI  - Does Helicobacter pylori cause gastric cancer via oxidative stress?
AB  - Epidemiologic evidence strongly supports a causal role for Helicobacter pylori in
      gastric carcinogenesis. The infection was recognized as a Class I human
      carcinogen by the International Agency for Research on Cancer in 1994. The
      bacterium does not induce carcinogenesis by itself. The present scientific
      consensus is that the bacterial oncogenic role is mediated by the chronic active
      inflammation it elicits in the gastric mucosa. Although the ultimate basic
      mechanism of carcinogenesis is unknown, strongly suggestive evidence points to
      oxidative stress as having a pivotal role in the process. This review discusses
      some of the evidence accumulated so far to support such a role. Numerous avenues
      of research are open and represent an intriguing challenge to the scientific
      community.

PMID- 16606333
TI  - Oxidative and nitrative DNA damage in animals and patients with inflammatory
      diseases in relation to inflammation-related carcinogenesis.
AB  - Infection and chronic inflammation are proposed to contribute to carcinogenesis
      through inflammation-related mechanisms. Infection with hepatitis C virus,
      Helicobacter pylori and the liver fluke, Opisthorchis viverrini (OV), are
      important risk factors for hepatocellular carcinoma (HCC), gastric cancer and
      cholangiocarcinoma, respectively. Inflammatory bowel diseases (IBDs) and oral
      diseases, such as oral lichen planus (OLP) and leukoplakia, are associated with
      colon carcinogenesis and oral squamous cell carcinoma (OSCC), respectively. We
      performed a double immunofluorescence labeling study and found that nitrative and
      oxidative DNA lesion products, 8-nitroguanine and 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG), were formed and inducible nitric oxide synthase (iNOS)
      was expressed in epithelial cells and inflammatory cells at the site of
      carcinogenesis in humans and animal models. Antibacterial, antiviral and
      antiparasitic drugs dramatically diminished the formation of these DNA lesion
      markers and iNOS expression. These results suggest that oxidative and nitrative
      DNA damage occurs at the sites of carcinogenesis, regardless of etiology.
      Therefore, it is considered that excessive amounts of reactive nitrogen species
      produced via iNOS during chronic inflammation may play a key role in
      carcinogenesis by causing DNA damage. On the basis of our results, we propose
      that 8-nitroguanine is a promising biomarker to evaluate the potential risk of
      inflammation-mediated carcinogenesis.

PMID- 16606334
TI  - Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids.
AB  - Genomes and their precursor nucleotides are highly exposed to reactive oxygen
      species, which are generated both as byproducts of oxygen respiration or
      molecular executors in the host defense, and by environmental exposure to
      ionizing radiation and chemicals. To counteract such oxidative damage in nucleic
      acids, mammalian cells are equipped with three distinct enzymes. MTH1 protein
      hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-2'
      deoxyguanosine triphosphate and 2-hydroxy-2'-deoxyadenosine triphosphate (2-OH
      dATP), to the corresponding monophosphates. We observed increased susceptibility
      to spontaneous carcinogenesis in MTH1-null mice, which exhibit an increased
      occurrence of A:T-->C:G and G:C-->T:A transversion mutations. 8-Oxoguanine (8
      oxoG) DNA glycosylase, encoded by the OGG1 gene, and adenine DNA glycosylase,
      encoded by the MUTYH gene, are responsible for the suppression of G:C to T:A
      transversions caused by the accumulation of 8-oxoG in the genome. Deficiency of
      these enzymes leads to increased tumorigenesis in the lung and intestinal tract
      in mice, respectively. MUTYH deficiency may also increase G:C to T:A
      transversions through the misincorporation of 2-OH-dATP, especially in the
      intestinal tract, since MUTYH can excise 2-hydroxyadenine opposite guanine in
      genomic DNA and the repair activity is selectively impaired by a mutation found
      in patients with autosomal recessive colorectal adenomatous polyposis.

PMID- 16606335
TI  - Concomitant suppression of hyperlipidemia and intestinal polyp formation by
      increasing lipoprotein lipase activity in Apc-deficient mice.
AB  - Epidemiologically, a high-fat diet is associated with the risk of colon cancer.
      In addition, serum levels of triglycerides (TGs) and cholesterol have been
      demonstrated to be positively associated with colon carcinogenesis. We recently
      found that an age-dependent hyperlipidemic state (high serum TG levels) exists in
      Apc-deficient mice, an animal model for human familial adenomatous polyposis. The
      mRNA levels of lipoprotein lipase (LPL), which catalyzes TG hydrolysis, were
      shown to be downregulated in the liver and intestines of mice. Moreover,
      treatment with a peroxisome proliferator-activated receptor (PPAR) alpha agonist,
      bezafibrate, or a PPARgamma agonist, pioglitazone, suppressed both hyperlipidemia
      and intestinal polyp formation in the mice, with induction of LPL mRNA. PPARalpha
      and PPARgamma agonists are reported to exert anti-proliferative and pro-apoptotic
      effects in cancer cells. One compound that also increases LPL expression levels
      but does not possess PPAR agnostic activity is NO-1886. When given at 400 or 800
      ppm in the diet, it suppresses both hyperlipidemia and intestinal polyp formation
      in Apc-deficient mice, with elevation of LPL mRNA. In conclusion, a decrease in
      serum lipid levels by increasing LPL activity may contribute to a reduction in
      intestinal polyp formation with Apc deficiency. PPARalpha and PPARgamma agonists,
      as well as NO-1886, could be useful as chemopreventive agents for colon cancer.

PMID- 16606336
TI  - Cancer-preventive anti-oxidants that attenuate free radical generation by
      inflammatory cells.
AB  - Active inflammatory leukocytes are a major endogenous source of reactive oxygen
      and nitrogen oxide species (RONS). We have recently established novel bioassay
      systems, in which either phorbol ester-stimulated, differentiated HL-60 human
      leukemia cells or lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages
      were co-cultured with AS52 Chinese hamster ovary cells. Extensive screening of
      extracts from Asian vegetables and fruits led to the identification of 1'
      acetoxychavicol acetate (ACA), auraptene, nobiletin, and zerumbone, all of which
      were found to be highly anti-mutagenic in the above co-culture systems.
      Pretreatment of RAW264.7 macrophages with LPS led to the activation of mitogen
      activated protein kinases (MAPKs) and Akt, together with the degradation of
      IkappaB-alpha protein, and the resultant activation of the AP-1, NF-kappaB, and
      CREB transcription factors. ACA abrogated ERK1/2 and JNK1/2, but not p38
      activation, as well as the activation and transcriptional activation of NF-kappaB
      and CREB, whereas nobiletin allowed phosphorylation of these MAPKs, while it
      suppressed AP-1, NF-kappaB, and CREB activation. Interestingly, zerumbone did not
      have any effects on the latter transcription factors, although it did attenuate
      iNOS mRNA expression. In addition, auraptene suppressed iNOS protein production,
      but not mRNA expression, implying that it targets the translation step. Our model
      systems may be useful for identifying potentially anti-carcinogenic inhibitors of
      RONS generation.

PMID- 16606337
TI  - Evidence for attenuated cellular 8-oxo-7,8-dihydro-2'-deoxyguanosine removal in
      cancer patients.
AB  - Measurement of the products of oxidatively damaged DNA in urine is a frequently
      used means by which oxidative stress may be assessed non-invasively. We believe
      that urinary DNA lesions, in addition to being biomarkers of oxidative stress,
      can potentially provide more specific information, for example, a reflection of
      repair activity. We used high-performance liquid chromatography prepurification,
      with gas chromatography-mass spectrometry (LC-GC-MS) and ELISA to the analysis of
      a number of oxidative [e.g., 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo
      7,8-dihydro-guanine, 5-(hydroxymethyl)uracil], non-oxidative (cyclobutane thymine
      dimers) and oligomeric DNA products in urine. We analysed spot urine samples from
      20 healthy subjects, and 20 age- and sex-matched cancer patients. Mononuclear
      cell DNA 8-oxodG levels were assessed by LC-EC. The data support our proposal
      that urinary DNA lesion products are predominantly derived from DNA repair.
      Furthermore, analysis of DNA and urinary 8-oxodG in cancer patients and controls
      suggested reduced repair activity towards this lesion marker in these patients.

PMID- 16606338
TI  - The roles of ATP in the dynamics of the actin filaments of the cytoskeleton.
AB  - In contrast to the actin filaments of muscle, which are stabilized by special
      proteins, actin filaments of the cytoskeleton are highly dynamic. In vitro
      observations at room temperature have led to the conclusion that the hydrolysis
      of ATP, which accompanies the polymerization of ATP-containing monomers,
      destabilizes the filaments of the actin skeleton. Many functions of this
      skeleton, such as signal transduction, the anchoring of cell adhesion complexes,
      and the transfer and generation of pulling forces, can obviously only be
      adequately performed by stable filaments. Here it is assumed that, at room
      temperature, the interaction of ADP-containing monomers is impaired by complexed
      water molecules that partly shield the binding surfaces. The possibility that, at
      higher temperatures, the interaction of the monomers is strong enough to prevent
      spontaneous filament depolymerization is explored. Using mechanical models that
      take into account binding forces and energies, the polymerization cycle expected
      under these conditions is described. It is shown that ATP serves primarily to
      prevent incorrect binding of the incoming monomer to the end of the filament
      ('adjusted fit'). In addition, it provides the free energy needed for disassembly
      of the expected stable filaments.

PMID- 16606339
TI  - Chiral distinction between the enantiomers of bicyclic alcohols by UDP
      glucuronosyltransferases 2B7 and 2B17.
AB  - The stereoselective binding and transformation of optically pure bicyclic
      alcohols by human UDP-glucuronosyltransferases from subfamily 2B were
      investigated. The enantiomers of 1-indanol, 1-tetralol, and 1-benzosuberol were
      synthesized by asymmetric Corey-Bakshi-Shibata reduction and subjected to
      glucuronidation assays. The alcohols studied were primarily glucuronidated by
      UGT2B7 and UGT2B17. The catalytic transformation by UGT2B17 was highly
      stereoselective, favoring conjugation of the (R)-enantiomers. UGT2B7, on the
      other hand, did not exhibit stereoselectivity toward 1-benzosuberol, the best
      substrate in this series. To assess binding affinities to the enzymes, the six
      different compounds were tested for their efficiency as inhibitors of either
      UGT2B7 or UGT2B17. The results of the latter analyses indicated that the
      affinities of both enantiomers of each pair towards UGT2B7 and UGT2B17 were of
      the same order of magnitude. Therefore, the findings of this study suggest that
      the spatial arrangement of the hydroxy group plays an important role in the
      glucuronic acid transfer reaction, but not necessarily in substrate binding to
      the UGTs.

PMID- 16606340
TI  - A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism
      on expression, activity, intracellular localisation and insight into the
      regulatory mechanisms.
AB  - The immunoproteasome subunit low molecular weight protein 2 (LMP2) codon 60
      polymorphism has been associated with autoimmune diseases. It has also been
      demonstrated to influence susceptibility to TNF-alpha-induced apoptosis in blood
      cells and proteasome activity in aged human brain. In the present study, an in
      silico model of immunoproteasome was used to examine the effect of the R60H
      polymorphism in the LMP2 subunit. The investigation of immunoproteasome
      expression, activity and intracellular localisation in an in vitro cellular
      model, namely lymphoblastoid cell lines, showed no major variations in
      functionality and amount, while a significant difference in antibody affinity was
      apparent. These data were integrated with previous results obtained in different
      tissues and combined with a structural model of the LMP2 polymorphism.
      Accordingly, we identified three prospective mechanisms that could explain the
      biological data for the polymorphism, such as modulation of the binding affinity
      of a putative non-catalytic modifier site on the external surface of the
      immunoproteasome core, or the modification of any channel between alpha and beta
      rings.

PMID- 16606342
TI  - Comparative proteomic analysis of neoplastic and non-neoplastic germ cell tissue.
AB  - A comparative proteomic analysis of neoplastic versus non-neoplastic seminoma
      identified glutathione S-transferase M3 as a differentially expressed protein.
      This expression difference could also be observed at the mRNA level, implying
      neoplasm-associated alterations in transcriptional or post-transcriptional
      mechanisms.

PMID- 16606341
TI  - Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet
      function.
AB  - Kinins are potent vasoactive peptides generated in blood and tissues by the
      kallikrein serine proteases. Two distinct kinin receptors have been described,
      one constitutive (subtype B2) and one inducible (subtype B1), and many
      physiological functions have been attributed to these receptors, including
      glucose homeostasis and control of vascular permeability. In this study we show
      that mice lacking the kinin B1 receptor (B1-/- mice) have lower fasting plasma
      glucose concentrations but exhibit higher glycemia after feeding when compared to
      wild-type mice. B1-/- mice also present pancreas abnormalities, characterized by
      fewer pancreatic islets and lower insulin content, which leads to hypoinsulinemia
      and reduced insulin release after a glucose load. Nevertheless, an insulin
      tolerance test indicated higher sensitivity in B1-/- mice. In line with this
      phenotype, pancreatic vascular permeability was shown to be reduced in B1
      receptor-ablated mice. The B1 agonist desArg9bradykinin injected intravenously
      can induce the release of insulin into serum, and this effect was not observed in
      the B1-/- mice or in isolated islets. Our data demonstrate the importance of the
      kinin B1 receptor in the control of pancreatic vascular homeostasis and insulin
      release, highlighting a new role for this receptor in the pathogenesis of
      diabetes and related diseases.

PMID- 16606343
TI  - BID, an interaction partner of protein kinase CK2alpha.
AB  - Recombinant murine BID protein was used as an in vitro substrate for the CK2
      holoenzyme and the catalytic CK2alpha subunit. The results obtained show that BID
      can only serve as a substrate for the catalytic CK2alpha subunit. Phosphorylation
      of BID using the CK2 holoenzyme was only possible in the presence of polylysine,
      supporting the notion that BID behaves similarly to calmodulin. Co
      immunoprecipitation of BID and CK2 subunits revealed that BID is preferentially
      associated with the CK2alpha subunit. Enzyme kinetic analyses yielded a Km value
      for BID that is a level of magnitude lower than that measured for casein and the
      synthetic peptide, suggesting more specific and tight binding of BID to CK2alpha.
      In contrast are the Vmax values observed, with a significantly higher
      phosphorylation rate measured for casein and the synthetic peptide than for BID.
      When BID was phosphorylated by polylysine-stimulated CK2 holoenzyme prior to
      caspase-8 cleavage, the formation of tC-BID was reduced in comparison to
      treatment with caspase-8 in the absence of protein kinase. Mass spectrometric
      analysis of BID phosphorylated by CK2alpha before and after cleavage with caspase
      8 showed phosphorylation of residues Thr58 and Ser76.

PMID- 16606344
TI  - Monomeric and dimeric GDF-5 show equal type I receptor binding and
      oligomerization capability and have the same biological activity.
AB  - Growth and differentiation factor 5 (GDF-5) is a homodimeric protein stabilized
      by a single disulfide bridge between cysteine 465 in the respective monomers, as
      well as by three intramolecular cysteine bridges within each subunit. A mature
      recombinant human GDF-5 variant with cysteine 465 replaced by alanine (rhGDF-5
      C465A) was expressed in E. coli, purified to homogeneity, and chemically
      renatured. Biochemical analysis showed that this procedure eliminated the sole
      interchain disulfide bond. Surprisingly, the monomeric variant of rhGDF-5 is as
      potent in vitro as the dimeric form. This could be confirmed by alkaline
      phosphatase assays and Smad reporter gene activation. Furthermore, dimeric and
      monomeric rhGDF-5 show comparable binding to their specific type I receptor,
      BRIb. Studies on living cells showed that both the dimeric and monomeric rhGDF-5
      induce homomeric BRIb and heteromeric BRIb/BRII oligomers. Our results suggest
      that rhGDF-5 C465A has the same biological activity as rhGDF-5 with respect to
      binding to, oligomerization of and signaling through the BMP receptor type Ib.

PMID- 16606345
TI  - Novel ketomethylene inhibitors of angiotensin I-converting enzyme (ACE):
      inhibition and molecular modelling.
AB  - Inhibition of angiotensin I-converting enzyme (ACE) has become an effective
      strategy in the treatment of hypertension and cardiovascular disease. Keto-ACE, a
      previously described C-domain selective ACE inhibitor, was used as the basis for
      the design, synthesis and molecular modelling of a series of novel ketomethylene
      derivatives for which ACE inhibition profiles and structural characterisation are
      reported. Ki determinations indicated that the introduction of a bulky aromatic
      tryptophan at the P2' position of keto-ACE significantly increased selectivity
      for the C-domain, while an aliphatic P2 Boc group conferred N-domain selectivity.
      These data were supported by the potential energies of the compounds docked with
      the C- and N-domains of ACE.

PMID- 16606346
TI  - Identification of trypsin I as a candidate for influenza A virus and Sendai virus
      envelope glycoprotein processing protease in rat brain.
AB  - Extracellular cleavage of virus envelope fusion glycoprotein hemagglutinin (HA0)
      by host trypsin-like proteases is a prerequisite for the infectivity and
      pathogenicity of human influenza A viruses and Sendai virus. The common epidemic
      influenza A viruses are pneumotropic, but occasionally cause encephalopathy or
      encephalitis, although the HA0 processing enzyme in the brain has not been
      identified. In searching for the brain processing proteases, we identified a
      processing enzyme in rat brain that was inducible by infection with these
      viruses. The purified enzyme exhibited an apparent molecular mass of
      approximately 22 kDa on SDS-PAGE and the N-terminal amino acid sequence was
      consistent with that of rat pancreatic trypsin I. Its substrate specificities and
      inhibition profiles were the same as those of pancreatic trypsin I. In situ
      hybridization and immunohistochemical studies on trypsin I distribution revealed
      heavy deposits in the brain capillaries, particularly in the allocortex, as well
      as in clustered neuronal cells of the hippocampus. The purified enzyme
      efficiently processed the HA0 of human influenza A virus and the fusion
      glycoprotein precursor of Sendai virus. Our results suggest that trypsin I in the
      brain potentiates virus multiplication in the pathogenesis and progression of
      influenza-associated encephalopathy or encephalitis.

PMID- 16606347
TI  - A fluorescence assay for rapid detection of ligand binding affinity to HIV-1
      gp41.
AB  - The fusion-active conformation of the envelope protein gp41 of HIV-1 consists of
      an N-terminal trimeric alpha-helical coiled-coil domain and three anti-parallel C
      terminal helices that fold down the grooves of the coiled-coil to form a six
      helix bundle. Disruption of the six-helix bundle is considered to be a key
      component of an effective non-peptide fusion inhibitor. In the current study, a
      fluorescence resonance energy transfer (FRET) experiment for the detection of
      inhibitor binding to the gp41 N-peptide coiled-coil of HIV-1 was performed,
      utilizing peptide inhibitors derived from the gp41 C-terminal helical region. The
      FRET acceptor is a 31-residue N-peptide containing a known deep hydrophobic
      pocket, stabilized into a trimer by ferrous ion ligation. The FRET donor is a 16
      18-residue fluorophore-labeled C-peptide, designed to test the specificity of the
      N-C interaction. Low microM dissociation constants were observed, correlated to
      the correct sequence and helical propensity of the C-peptides. Competitive
      inhibition was demonstrated using the assay, allowing for rank ordering of
      peptide inhibitors according to their affinity in the 1-20 microM range. The
      assay was conducted by measuring fluorescence intensity in 384-well plates. The
      rapid detection of inhibitor binding may permit identification of novel drug
      classes from a library.

PMID- 16606349
TI  - Functional correlates of anal canal anatomy: puborectalis muscle and anal canal
      pressure.
AB  - BACKGROUND: Resting and squeeze pressures in the anal canal are thought to
      reflect the contributions of the internal anal sphincter (IAS) and the external
      anal sphincter (EAS) respectively. Role of the puborectalis muscle (PRM) in the
      genesis of anal canal pressure is not known. OBJECTIVES: To determine the
      functional correlates of anal canal anatomy. METHODS: Seventeen asymptomatic
      nulliparous women were studied using simultaneous 3D ultrasound images and
      manometry of the anal canal. Ultrasound images were recorded using a transducer
      placed at the vaginal introitus and pressures were recorded with a side-hole
      manometry catheter using a station (every 5 mm) pull-through technique. Pressures
      were recorded at rest and during voluntary squeeze. RESULTS: Anal canal high
      pressure zone was 39 +/- 1 mm in length. The IAS, EAS, and PRM were clearly
      visualized in the ultrasound images. EAS was located in the distal (length 19 +/-
      1 mm) and PRM in the proximal part (length 18 +/- 1 mm) of the anal canal. The
      station pull-through technique revealed increases in pressure with voluntary
      squeeze in the proximal as well as distal parts of the anal canal. Proximal anal
      canal pressure, located in the PRM zone, showed greater circumferential asymmetry
      than the distal anal canal pressure, located in the EAS zone. CONCLUSIONS: (1)
      PRM contributes to the squeeze pressure in the proximal part of the anal canal
      and EAS to the distal anal canal. (2) PRM squeeze-related increase in anal canal
      pressure might be important in the anal continence mechanism.

PMID- 16606348
TI  - Role of pyruvate dehydrogenase kinase isoenzyme 4 (PDHK4) in glucose homoeostasis
      during starvation.
AB  - The PDC (pyruvate dehydrogenase complex) is strongly inhibited by phosphorylation
      during starvation to conserve substrates for gluconeogenesis. The role of PDHK4
      (pyruvate dehydrogenase kinase isoenzyme 4) in regulation of PDC by this
      mechanism was investigated with PDHK4-/- mice (homozygous PDHK4 knockout mice).
      Starvation lowers blood glucose more in mice lacking PDHK4 than in wild-type
      mice. The activity state of PDC (percentage dephosphorylated and active) is
      greater in kidney, gastrocnemius muscle, diaphragm and heart but not in the liver
      of starved PDHK4-/- mice. Intermediates of the gluconeogenic pathway are lower in
      concentration in the liver of starved PDHK4-/- mice, consistent with a lower rate
      of gluconeogenesis due to a substrate supply limitation. The concentration of
      gluconeogenic substrates is lower in the blood of starved PDHK4-/- mice,
      consistent with reduced formation in peripheral tissues. Isolated diaphragms from
      starved PDHK4-/- mice accumulate less lactate and pyruvate because of a faster
      rate of pyruvate oxidation and a reduced rate of glycolysis. BCAAs (branched
      chain amino acids) are higher in the blood in starved PDHK4-/- mice, consistent
      with lower blood alanine levels and the importance of BCAAs as a source of amino
      groups for alanine formation. Non-esterified fatty acids are also elevated more
      in the blood of starved PDHK4-/- mice, consistent with lower rates of fatty acid
      oxidation due to increased rates of glucose and pyruvate oxidation due to greater
      PDC activity. Up-regulation of PDHK4 in tissues other than the liver is clearly
      important during starvation for regulation of PDC activity and glucose
      homoeostasis.

PMID- 16606350
TI  - A strong association between down-regulation of HLA-DR expression and the late
      mortality in patients with severe acute pancreatitis.
AB  - OBJECTIVES: There is no reliable parameter to predict the late mortality of
      patients with severe acute pancreatitis though it is an important issue. Recently
      a proposed parameter for "immunoparalysis," a down-regulation of Human Leukocytes
      Antigens-DR (HLA-DR) expression on monocytes, had been detected in patients with
      severe but not mild acute pancreatitis. However, the relationship between this
      parameter and late mortality of acute pancreatitis is still unclear. Therefore,
      we conducted this study in order to elucidate this issue. METHODS: Twenty-five
      patients of severe acute pancreatitis admitted to Chang-Gung Memorial Hospital
      were successively enrolled during the period of 1999-2002. The HLA-DR expression,
      and serum levels of interleukin-10 (IL-10) and tumor necrosis factor-alpha (TNF
      alpha) at different time points were measured. The HLA-DR expression was
      evaluated by flow cytometry and the levels of IL-10 and TNF-alpha were measured
      by ELISA. RESULTS: In our series, there were 7 (28%) late mortality cases out of
      25 patients with severe acute pancreatitis. When analyzing the serial change of
      HLA-DR expression, it is clear that in survival group the HLA-DR expression was
      gradually up-regulated and in late mortality group it was persistently down
      regulated (p < 0.001). When comparing with other parameters like Acute
      Physiological and Chronic Health Evaluation II and Ranson's score by Cox hazards
      model, the HLA-DR expression on 10th day (HLA-DR-10) gave the only statistically
      significant correlation with late mortality (p = 0.001). Furthermore, HLA-DR10 is
      also a good predictor for late mortality when analyzed by receiver-operating
      characteristics (ROC) curves with 0.944 area under ROC (AUROC) value. The optimal
      cutoff value of HLA-DR on 10th day for predicting late mortality was 52.3% with
      94.4% sensitivity and 85.7% specificity. As for the serum levels of TNF-alpha and
      IL-10, there were significant persistently higher levels in late mortality group
      than in survival group (p < 0.05). Furthermore, these monocytes from severe acute
      pancreatitis were with partial restoration of HLA-DR expression but with normal
      TNF-alpha and IL-10 secretion ability when stimulated in vitro with LPS.
      CONCLUSIONS: In severe acute pancreatitis, there was a strong association between
      the persistent down-regulation of HLA-DR expression and the late mortality.
      Furthermore, a cutoff value of 52.3% of HLA-DR expressed monocytes on the 10th
      hospitalization day is a good predictor for late mortality in patients with
      severe acute pancreatitis.

PMID- 16606351
TI  - Factors associated with the development of intestinal strictures or obstructions
      in patients with Crohn's disease.
AB  - OBJECTIVE: Theoretical concern exists that rapid luminal healing in Crohn's
      disease (CD) with therapies like infliximab increases the risk of intestinal
      stenosis, stricture, or obstruction (SSOs). METHODS: Data were analyzed from the
      ongoing observational TREAT (the Crohn's Therapy, Resource, Evaluation, and
      Assessment Tool) Registry and ACCENT I (A Crohn's Disease Clinical Trial
      Evaluating Infliximab in a New Long-Term Treatment Regimen) study. Investigators
      reported SSOs as adverse events or serious adverse events. RESULTS: In TREAT,
      SSOs occurred at a significantly higher rate in patients treated with infliximab
      compared with patients who received other treatments only (1.95 events/100
      patient-years vs 0.99 events/100 patient-years; p < 0.001). Using multivariable
      analyses, however, infliximab therapy was not associated with SSO development. CD
      severity at the time of event onset (hazard ratio (HR) = 2.35, 95% confidence
      internal (CI) 1.35-4.09); CD duration (HR = 1.02, 95% CI 1.00-1.04); ileal
      disease (HR = 1.56, 95% CI 1.04-2.36); and new corticosteroid use (HR = 2.85, 95%
      CI 1.23-6.57) were associated with SSOs. In ACCENT I, no increase in SSOs was
      reported in patients who received infliximab maintenance therapy compared with
      those who received episodic therapy, despite higher median cumulative infliximab
      exposure. Additionally, there was no increase in SSO development with rapid
      mucosal healing (healing at week 10). CONCLUSIONS: Although unadjusted analyses
      suggested that patients who received infliximab were twice as likely to develop
      SSOs, multivariable analysis adjusting for other factors demonstrated that only
      disease duration, disease severity, ileal disease, and new corticosteroid use
      were significantly associated with SSO development.

PMID- 16606352
TI  - Incidence of ischemic colitis and serious complications of constipation among
      patients using alosetron: systematic review of clinical trials and post-marketing
      surveillance data.
AB  - BACKGROUND: Ischemic colitis and serious complications of constipation have been
      reported in association with the use of alosetron, which is approved for women
      with severe diarrhea-predominant IBS who have failed conventional therapies. This
      systematic review calculated the incidence of these adverse events in alosetron
      using patients in clinical trials and post-marketing surveillance. METHODS: A
      panel of experts in epidemiology and functional bowel disorders reviewed clinical
      trial report forms and FDA MedWatch forms of each reported case of ischemic
      colitis or serious complications of constipation. Experts were blinded about
      whether patients used alosetron or placebo. Using pre-specified criteria, experts
      rated the likelihood of an accurate diagnosis and an association between
      medication use and adverse events. Cases that were not consistent with the
      reported diagnosis or not possibly associated with medication use were eliminated
      from calculation of incidence rates of adverse events. RESULTS: Pooled data from
      clinical trials indicate an increased rate of ischemic colitis among alosetron
      using patients compared to placebo-using patients (0.15%vs 0.0%, respectively, p
      = 0.03), but there was no significant difference in the rate of serious
      complications of constipation. All (19/19) alosetron-using patients with ischemic
      colitis had reversible colitis without long-term sequelae. Based on post
      marketing surveillance data, the post-adjudication rate of ischemic colitis is
      1.1 per 1,000 patient-years of alosetron use and the rate of serious
      complications of constipation is 0.66 per 1,000 patient-years of alosetron use.
      CONCLUSION: The incidence of ischemic colitis and serious complications of
      constipation is very low and is rarely associated with long-term sequelae or
      serious morbidity.

PMID- 16606353
TI  - Oligodendrocyte excitotoxicity determined by local glutamate accumulation and
      mitochondrial function.
AB  - Developing oligodendrocytes (OL precursors, pre-OLs) express alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype glutamate receptors
      (AMPARs) and are highly vulnerable to hypoxic-ischemic or oxygen-glucose
      deprivation (OGD)-induced excitotoxic injury, yet the mechanisms of injury remain
      unclear. Here we investigated the role of glutamate accumulation and
      mitochondrial function in OGD-induced pre-OL toxicity in vitro. Bulk glutamate
      concentration in the culture medium did not increase during OGD and OGD
      conditioned medium did not transfer toxicity to naive cells. Facilitation of
      glutamate diffusion by constant agitation of the culture reduced, while
      inhibition of glutamate diffusion by increasing medium viscosity with dextran
      enhanced, OGD-induced pre-OL injury. Depletion of extracellular glutamate by the
      glutamate scavenging system, glutamate-pyruvate transaminase plus pyruvate,
      attenuated pre-OL injury during OGD. Together these data suggest that local
      glutamate accumulation is critical for OGD toxicity. Interestingly, under
      normoxic conditions, addition of glutamate to pre-OLs did not cause receptor
      mediated toxicity, but the toxicity could be unmasked by mitochondrial impairment
      with mitochondrial toxins. Furthermore, OGD caused mitochondrial potential
      collapse that was independent of AMPAR activation, and OGD toxicity was enhanced
      by mitochondrial toxins. These data demonstrate that pre-OL excitotoxicity is
      exacerbated by mitochondrial dysfunction during OGD. Overall, our results
      indicate that OGD-induced pre-OL injury is a novel form of excitotoxicity caused
      by the combination of local glutamate accumulation that occurs without an
      increase in bulk glutamate concentration and mitochondrial dysfunction.
      Therapeutic strategies targeting local glutamate concentration and mitochondrial
      injury during hypoxia-ischemia may be relevant to human disorders associated with
      pre-OL excitotoxicity.

PMID- 16606354
TI  - Functional analysis of a mammalian odorant receptor subfamily.
AB  - Phylogenetic analysis groups mammalian odorant receptors into two broad classes
      and numerous subfamilies. These subfamilies are proposed to reflect functional
      organization. Testing this idea requires an assay allowing detailed functional
      characterization of odorant receptors. Here we show that a variety of Class I and
      Class II mouse odorant receptors can be functionally expressed in Xenopus laevis
      oocytes. Receptor constructs included the N-terminal 20 residues of human
      rhodopsin and were co-expressed with Galphaolf and the cystic fibrosis
      transmembrane regulator to allow electrophysiological measurement of receptor
      responses. For most mouse odorant receptors tested, these conditions were
      sufficient for functional expression. Co-expression of accessory proteins was
      required to allow functional surface expression of some mouse odorant receptors.
      We used this assay to examine the receptive ranges of all members of the mouse
      odorant receptor 42 (MOR42) subfamily. MOR42-1 responded to dicarboxylic acids,
      preferring a 10-12 carbon chain length. MOR42-2 responded to monocarboxylic acids
      (7-10 carbons). MOR42-3 responded to dicarboxylic acids (8-10 carbons) and
      monocarboxylic acids (10-12 carbons). Thus, the receptive range of each receptor
      was unique. However, overlap between the individual receptive ranges suggests
      that the members of this subfamily form one contiguous subfamily receptive range,
      suggesting that odorant receptor subfamilies do constitute functional units.

PMID- 16606355
TI  - Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO,
      a new agonist radiotracer for imaging the high-affinity state of D2 receptors in
      vivo using positron emission tomography.
AB  - [11C]-(+)-PHNO (4-propyl-9-hydroxynaphthoxazine) is a new agonist radioligand
      that provides a unique opportunity to measure the high-affinity states of the D2
      receptors (D2-high) using positron emission tomography (PET). Here we report on
      the distribution, displaceablity, specificity and modeling of [11C]-(+)-PHNO and
      compare it with the well characterized antagonist D2 radioligand,
      [11C]raclopride, in cat. [11C]-(+)-PHNO displayed high uptake in striatum with a
      mean striatal binding potential (BP) of 3.95 +/- 0.85. Pre-treatment with
      specific D1 (SCH23390), D2 (raclopride, haloperidol) and D3 receptor (SB-277011)
      antagonists indicated that [11C]-(+)-PHNO binding in striatum is specific to D2
      receptors. Within-subject comparisons showed that [11C]-(+)-PHNO BP in striatum
      was almost 2.5-fold higher than that measured with [11C]-(-)-NPA ([11C]-(-)-N
      propyl-norapomorphine). Comparison of the dose-effect of amphetamine (0.1, 0.5
      and 2 mg/kg; i.v.) showed that [11C]-(+)-PHNO was more sensitive to the dopamine
      releasing effect of amphetamine than [11C]raclopride. Amphetamine induced up to
      83 +/- 4% inhibition of [11C]-(+)-PHNO BP and only up to 56 +/- 8% inhibition of
      [11C]raclopride BP. Scatchard analyses of [11C]-(+)-PHNO and [11C]raclopride
      bindings in two cats showed that the Bmax obtained with the agonist (29.6 and
      32.9 pmol/mL) equalled that obtained with the antagonist (30.6 and 33.4 pmol/mL).
      The high penetration of [11C]-(+)-PHNO in brain, its high signal-to-noise ratio,
      its favorable in vivo kinetics and its high sensitivity to amphetamine shows that
      [11C]-(+)-PHNO has highly suitable characteristics for probing the D2-high with
      PET.

PMID- 16606357
TI  - Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in
      developing and adult mouse brain.
AB  - The c-Jun N-terminal kinase (JNK) is one of the three major mitogen-activated
      protein kinases (MAPKs) playing key roles in various cellular processes in
      response to both extracellular and intracellular stimuli. JNK/SAPK-associated
      protein 1 (JSAP1 also referred to as JIP3) is a JNK-associated scaffold that
      controls the specificity and efficiency of JNK signaling cascades. Here we
      studied its expression in mouse brains. JSAP1 mRNA was expressed in developing
      and adult brains, showing spatial patterns similar to JNK1-3 mRNAs. In embryos,
      JSAP1 immunolabeling was intense for progenitor cells in the ventricular zone
      throughout the brain and in the external granular layer of the cerebellum, and
      for neurons and glial cells differentiating in the mantle zone. In adults, JSAP1
      was distributed in various neurons and Bergmann glia, with higher levels in
      striatal cholinergic interneurons, telencephalic parvalbumin-positive
      interneurons and cerebellar Purkinje cells. In these neurons, JSAP1 was observed
      as tiny particulate staining in spines, dendrites, perikarya and axons, where it
      was often associated with the smooth endoplasmic reticulum (sER) and cell
      membrane. Immunoblots revealed enriched distribution in the microsomal fraction
      and cytosolic fraction. Therefore, the characteristic cellular expression and
      subcellular distribution of JSAP1 might be beneficial for cells to efficiently
      link external stimuli to the JNK MAPK pathway and other intracellular
      machineries.

PMID- 16606358
TI  - Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing
      synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid receptor.
AB  - A class of scaffolding protein containing the post-synaptic density-95/Dlg/ZO-1
      (PDZ) domain is thought to be involved in synaptic trafficking of alpha-amino-3
      hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors during development.
      To clarify the molecular mechanism of AMPA receptor trafficking, we performed a
      yeast two-hybrid screening system using the cytoplasmic tail of the GluR1 subunit
      of AMPA receptor as a bait and identified a synaptic molecule, Shank3/ProSAP2, as
      a GluR1 subunit-interacting molecule. Shank3 is a PDZ domain-containing
      multidomain protein and is predominantly expressed in developing neurons. Using
      the glutathione S-transferase pull-down assay and immunoprecipitation technique
      we demonstrated that the GluR1 subunit directly binds to the PDZ domain of Shank3
      via its carboxyl terminal PDZ-binding motif. We raised anti-Shank3 antibody to
      investigate the expression of Shank3 in cortical neurons. The pattern of Shank3
      immunoreactivity was strikingly punctate, mainly observed in the spines, and
      closely matched the pattern of post-synaptic density-95 immunoreactivity,
      indicating that Shank3 is colocalized with post-synaptic density-95 in the same
      spines. When Shank3 and the GluR1 subunit were overexpressed in primary cortical
      neurons, they were also colocalized in the spines. Taken together with the
      biochemical interaction of Shank3 with the GluR1 subunit, these results suggest
      that Shank3 is an important molecule that interacts with GluR1 AMPA receptor at
      synaptic sites of developing neurons.

PMID- 16606359
TI  - Activation of 5-lipoxygenase after oxygen-glucose deprivation is partly mediated
      via NMDA receptor in rat cortical neurons.
AB  - 5-Lipoxygenase (5-LOX) is the enzyme metabolizing arachidonic acid to produce pro
      inflammatory leukotrienes. We have reported that 5-LOX is translocated to the
      nuclear envelope after ischemic-like injury in PC12 cells. In the present study,
      we determined whether 5-LOX is activated (translocation and production of
      leukotrienes) after oxygen-glucose deprivation (OGD) in primary rat cortical
      neurons; if so, whether this activation is mediated by NMDA receptor. After OGD,
      5-LOX was translocated to the nuclear envelope as detected by immunoblotting,
      immunostaining and green fluorescent protein-5-LOX transfection. 5-LOX
      metabolites, cysteinyl-leukotrienes (CysLTs) but not leukotriene B4, in the
      culture media were increased 0.5-1.5 h after recovery. Similarly, NMDA (100
      microm) also induced 5-LOX translocation, and increased the production of CysLTs
      during 0.5-1 h NMDA exposure. Both OGD and NMDA reduced neuron viability. NMDA
      receptor antagonist MK-801 inhibited almost all the responses to OGD and NMDA;
      whereas 5-LOX activating protein inhibitor MK-886 and 5-LOX inhibitor caffeic
      acid inhibited the reduction of neuron viability and the production of CysLTs,
      but did not affect 5-LOX translocation. From these results, we conclude that OGD
      can activate 5-LOX in primary rat cortical neurons, and that this activation may
      be partly mediated via activating NMDA receptor.

PMID- 16606360
TI  - Neprilysin activity and expression are controlled by nicastrin.
AB  - We recently demonstrated that the presenilin-dependent gamma-secretase complex
      regulates the expression and activity of neprilysin, one of the main enzymes that
      degrade the amyloid beta-peptide (Abeta) which accumulates in Alzheimer's
      disease. Here, we examined the influence of endogenous nicastrin (NCT), a member
      of the gamma-secretase complex, on neprilysin physiology. We show that nicastrin
      deficiency drastically lowers neprilysin expression, membrane-bound activity and
      mRNA levels, but it did not modulate the expression of two other putative Abeta
      cleaving enzymes, endothelin-converting enzyme and insulin-degrading enzyme.
      Furthermore, we show that nicastrin restores neprilysin activity and expression
      in nicastrin-deficient, but not presenilin-deficient fibroblasts, indicating that
      the control of neprilysin necessitates the complete gamma-secretase complex
      harbouring its four reported components. Finally, we show that NCT expression
      peaked 24 h after NCT cDNA transfection of wild-type and NCT-/- fibroblasts,
      while neprilysin expression drastically increased only after 36 h and was maximal
      at 48 h. This delayed effect on neprilysin expression correlates well with our
      demonstration of an indirect gamma-secretase-dependent modulation of neprilysin
      at its transcriptional level.

PMID- 16606361
TI  - Interaction between the vesicular glutamate transporter type 1 and endophilin A1,
      a protein essential for endocytosis.
AB  - In the nerve terminal, neurotransmitter is actively packaged into synaptic
      vesicles before its release by Ca2+-dependent exocytosis. The three vesicular
      glutamate transporters (VGLUT1, -2 and -3) are highly conserved proteins that
      display similar bioenergetic and pharmacological properties but are expressed in
      different brain areas. We used the divergent C-terminus of VGLUT1 as a bait in a
      yeast two-hybrid screen to identify and map the interaction between a proline
      rich domain of VGLUT1 and the Src homology domain 3 (SH3) domain of endophilin.
      We further confirmed this interaction by using different glutathione-S
      transferase-endophilin fusion proteins to pull down VGLUT1 from rat brain
      extracts. The expression profiles of the two genes and proteins were compared on
      rat brain sections, showing that endophilin is most highly expressed in regions
      and cells expressing VGLUT1. Double immunofluorescence in the rat cerebellum
      shows that most VGLUT1-positive terminals co-express endophilin, whereas VGLUT2
      expressing terminals are often devoid of endophilin. However, neither VGLUT1
      transport activity, endophilin enzymatic activity nor VGLUT1 synaptic targeting
      were altered by this interaction. Overall, the discovery of endophilin as a
      partner for VGLUT1 in nerve terminals strongly suggests the existence of
      functional differences between VGLUT1 and -2 terminals in their abilities to
      replenish vesicle pools.

PMID- 16606362
TI  - Caspase-dependent alteration of the ADP/ATP translocator triggers the
      mitochondrial permeability transition which is not required for the low-potassium
      dependent apoptosis of cerebellar granule cells.
AB  - We investigated ADP/ATP exchange mediated by the adenine nucleotide translocator
      and opening of the mitochondrial permeability transition pore in homogenates from
      cerebellar granule cells en route to apoptosis induced by low potassium. We
      showed that, in the first 3 h of apoptosis, when maximum cytochrome c release had
      already occurred, adenine nucleotide translocator function was impaired owing to
      the action of reactive oxygen species, but no permeability transition pore
      opening occurred. Over 3-8 h of apoptosis, the permeability transition pore
      progressively opened, owing to caspase action, and further ADP/ATP translocator
      impairment occurred. The kinetics of transport and permeability transition pore
      opening were inversely correlated, both in the absence and presence of inhibitors
      of antioxidant and proteolytic systems. We conclude that, en route to apoptosis,
      alteration of the adenine nucleotide translocator occurs, resulting in
      permeability transition pore opening. This process depends on the action of
      caspase on pore component(s) other than the ADP/ATP translocator, because no
      change in either amount or molecular weight of the latter protein was noted
      during apoptosis, as measured by western blotting. Cell death occurs via
      apoptosis in the presence of cyclosporin A, the permeability transition pore
      inhibitor, thus showing that permeability transition pore opening, not needed for
      cytochrome c release, is also unnecessary for apoptosis to occur.

PMID- 16606363
TI  - Hyperdopaminergia and altered locomotor activity in GABAB1-deficient mice.
AB  - GABAB1-/- mice, which are devoid of functional GABAB receptors, consistently
      exhibit marked hyperlocomotion when exposed to a novel environment. Telemetry
      recordings now revealed that, in a familiar environment, GABAB1-/- mice display
      an altered pattern of circadian activity but no hyperlocomotion. This indicates
      that hyperlocomotion is only triggered when GABAB1-/- mice are aroused by
      novelty. In microdialysis experiments, GABAB1-/- mice exhibited a 2-fold
      increased extracellular level of dopamine in the striatum. Following D
      amphetamine administration, GABAB1-/- mice released less dopamine than wild-type
      mice, indicative of a reduced cytoplasmic dopamine pool. The hyperdopaminergic
      state of GABAB1-/- mice is accompanied by molecular changes, including reduced
      levels of tyrosine hydroxylase mRNA, D1 receptor binding-sites and Ser40
      phosphorylation of tyrosine hydroxylase. Tyrosine hydroxylase activity, tissue
      dopamine content and dopamine metabolism do not appear to be measurably altered.
      Pharmacological and electrophysiological experiments support that the
      hyperdopaminergic state of GABAB1-/- mice is not severe enough to inactivate
      dopamine D2 receptors and to disrupt D2-mediated feedback inhibition of tyrosine
      hydroxylase activity. The data support that loss of GABAB activity results in a
      sustained moderate hyperdopaminergic state, which is phenotypically revealed by
      contextual hyperlocomotor activity. Importantly, the presence of an inhibitory
      GABA tone on the dopaminergic system mediated by GABAB receptors provides an
      opportunity for therapeutic intervention.

PMID- 16606364
TI  - Apolipoprotein A-I increases association of cytosolic cholesterol and caveolin-1
      with microtubule cytoskeletons in rat astrocytes.
AB  - Apolipoprotein (apo) A-I induces rapid translocation of protein kinase Calpha and
      phospholipase Cgamma, and slow translocation of caveolin-1 and newly synthesized
      cholesterol to the cytosolic lipid-protein particle (CLPP) fraction in rat
      astrocytes. In order to understand the function of CLPP, we investigated the
      interaction with cytoskeletons of CLPP-related proteins such as caveolin-1 and
      protein kinase Calpha and of CLPP-related lipids in rat astrocytes. Under the
      conditions that microtubules were depolymerized, association of cytosolic
      caveolin-1 with protein kinase Calpha and alpha-tubulin was enhanced when the
      cells were treated with apoA-I for 5 min. This association was suppressed by a
      scaffolding domain-peptide of caveolin-1. Association with the microtubule-like
      filaments of cytosolic lipids, caveolin-1 and protein kinase Calpha was also
      increased by the apoA-I treatment and inhibited by the scaffolding domain
      peptide. Paclitaxel (taxol), a compound to stabilize microtubules, suppressed the
      apoA-I-mediated intracellular translocation and release from the cells of the de
      novo synthesized cholesterol and phospholipid. The findings suggested that the
      association of CLPP with microtubules is mediated by a scaffolding domain of
      caveolin-1, induced by apoA-I and involved in regulation of intracellular
      cholesterol trafficking for assembly of cellular lipids to apoA-I-high-density
      lipoprotein (HDL).

PMID- 16606365
TI  - Nuclear factor-I regulates glial fibrillary acidic protein gene expression in
      astrocytes differentiated from cortical precursor cells.
AB  - The elucidation of the transcriptional mechanisms that regulate glial fibrillary
      acidic protein (GFAP) gene expression is important for the understanding of the
      molecular mechanisms that control astrocyte differentiation during brain
      development. We investigated regulatory elements located in a proximal region of
      the GFAP promoter, important for expression in cortical precursor cells
      differentiating into astrocytes. One of these elements recognizes transcription
      factors of the nuclear factor-I family (NFI). We found that, in primary cultures
      of cortical cells, NFI occupies the GFAP promoter prior to the induction of
      astrocyte differentiation. In the developing cerebral cortex, the onset of
      expression of NFI coincides chronologically with the beginning of
      astrocytogenesis. Mutational analysis of the GFAP gene and transfections in
      primary cortical precursors show that inhibition of binding of NFI to the GFAP
      promoter results in decreased levels of transcriptional activity and is required
      for the synergistic stimulation of the GFAP promoter by the astrogenic agents,
      pituitary adenylate cyclase-activating polypeptide and ciliary neurotrophic
      factor, which in combination enhance astrocyte differentiation to generate
      astrocytes with longer processes. Thus, NFI appears to be an important factor for
      the integration of astrogenic stimuli in the developing central nervous system.

PMID- 16606366
TI  - Plasma membrane ion permeability induced by mutant alpha-synuclein contributes to
      the degeneration of neural cells.
AB  - Mutations in alpha-synuclein cause some cases of familial Parkinson's disease
      (PD), but the mechanism by which alpha-synuclein promotes degeneration of
      dopamine-producing neurons is unknown. We report that human neural cells
      expressing mutant alpha-synuclein (A30P and A53T) have higher plasma membrane ion
      permeability. The higher ion permeability caused by mutant alpha-synuclein would
      be because of relatively large pores through which most cations can pass non
      selectively. Both the basal level of [Ca2+]i and the Ca2+ response to membrane
      depolarization are greater in cells expressing mutant alpha-synuclein. The
      membrane permeable Ca2+ chelator BAPTA-AM significantly protected the cells
      against oxidative stress, whereas neither L-type (nifedipine) nor N-type (omega
      conotoxin-GVIA) Ca2+ channel blockers protected the cells. These findings suggest
      that the high membrane ion permeability caused by mutant alpha-synuclein may
      contribute to the degeneration of neurons in PD.

PMID- 16606367
TI  - NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate,
      aspartate and GABA levels in the dorsal hippocampus following fluid percussion
      injury in the rat.
AB  - Traumatic brain injury (TBI) produces a rapid and excessive elevation in
      extracellular glutamate that induces excitotoxic brain cell death. The peptide
      neurotransmitter N-acetylaspartylglutamate (NAAG) is reported to suppress
      neurotransmitter release through selective activation of presynaptic group II
      metabotropic glutamate receptors. Therefore, strategies to elevate levels of NAAG
      following brain injury could reduce excessive glutamate release associated with
      TBI. We hypothesized that the NAAG peptidase inhibitor, ZJ-43 would elevate
      extracellular NAAG levels and reduce extracellular levels of amino acid
      neurotransmitters following TBI by a group II metabotropic glutamate receptor
      (mGluR)-mediated mechanism. Dialysate levels of NAAG, glutamate, aspartate and
      GABA from the dorsal hippocampus were elevated after TBI as measured by in vivo
      microdialysis. Dialysate levels of NAAG were higher and remained elevated in the
      ZJ-43 treated group (50 mg/kg, i.p.) compared with control. ZJ-43 treatment also
      reduced the rise of dialysate glutamate, aspartate, and GABA levels. Co
      administration of the group II mGluR antagonist, LY341495 (1 mg/kg, i.p.)
      partially blocked the effects of ZJ-43 on dialysate glutamate and GABA,
      suggesting that NAAG effects are mediated through mGluR activation. The results
      are consistent with the hypothesis that inhibition of NAAG peptidase may reduce
      excitotoxic events associated with TBI.

PMID- 16606368
TI  - N-acetylglucosaminyltranferase VB expression enhances beta1 integrin- dependent
      PC12 neurite outgrowth on laminin and collagen.
AB  - N-acetylglucosaminyltransferase VB (GnT-VB, -IX) is a newly discovered
      glycosyltransferase expressed exclusively in high levels in neuronal tissue
      during early development. Its homolog, GnT-V, is expressed in many tissues and
      modulates cell-cell and cell-matrix adhesion. The ability of GnT-VB to regulate
      cell-matrix interactions was initially investigated using the rat
      pheochromocytoma PC12 neurite outgrowth model. PC12 cells stably transfected with
      GnT-VB consistently showed an enhanced rate of nerve growth factor (NGF)-induced
      neurite outgrowth on collagen and laminin substrates. Levels of TrkA receptor
      phosphorylation and downstream ERK activation induced by NGF were not influenced
      by GnT-VB expression. No significant difference was observed in the rate of
      neurite outgrowth when cells were cultured on non-coated culture dishes,
      indicating that integrin-ECM interaction is required for the stimulatory effects.
      Neurite outgrowth induced by manganese-dependent activation of beta1 integrin on
      collagen and laminin substrates, however, showed a significant increase in
      neurite length for the PC12/GnT-VB cells, compared with control cells, suggesting
      that the enhancement is most likely mediated by alteration of beta1 integrin-ECM
      interaction by GnT-VB. These results demonstrate that GnT-VB expression can
      modulate the rate of neurite outgrowth by affecting beta1 integrin-ECM
      interaction.

PMID- 16606369
TI  - Pseudophosphorylation of tau at serine 422 inhibits caspase cleavage: in vitro
      evidence and implications for tangle formation in vivo.
AB  - The tangles of Alzheimer's disease (AD) are comprised of the tau protein
      displaying numerous alterations, including phosphorylation at serine 422 (S422)
      and truncation at aspartic acid 421 (D421). Truncation at the latter site appears
      to result from activation of caspases, a class of proteases that cleave
      specifically at aspartic acid residues. It has been proposed that phosphorylation
      at or near caspase cleavage sites could regulate the ability of the protease to
      cleave at those sites. Here, we use tau pseudophosphorylated at S422 (S422E) to
      examine the effects of tau phosphorylation on its cleavage by caspase 3. We find
      that S422E tau is more resistant to proteolysis by caspase 3 than non
      pseudophosphorylated tau. Additionally, we use antibodies directed against the
      phosphorylation site and against the truncation epitope to assess the presence of
      these epitopes in neurofibrillary tangles in the aged human brain. We show that
      phosphorylation precedes truncation during tangle maturation. Moreover, the
      distribution of the two epitopes suggests that a significant length of time
      (perhaps as much as two decades) elapses between S422 phosphorylation and
      cleavage at D421. We further conclude that tau phosphorylation at S422 may be a
      protective mechanism that inhibits cleavage in vivo.

PMID- 16606370
TI  - The metabolism of C-glucose by neurons and astrocytes in brain subregions
      following focal cerebral ischemia in rats.
AB  - To provide insights into the effects of temporary focal ischemia on the function
      of neurons and astrocytes in vivo, we measured the incorporation of radiolabel
      from [U-14C]glucose into both glutamate and glutamine in brain subregions at 1 h
      of reperfusion following occlusion of the middle cerebral artery for 2 or 3 h.
      Under the experimental conditions used, 14C-glutamate is mainly produced in
      neurons whereas 14C-glutamine is generated in astrocytes from 14C-glutamate of
      both neuronal and astrocytic origin. Radiolabel incorporation into both amino
      acids was greatly decreased. The change in 14C-glutamate accumulation provides
      strong evidence for substantial reductions in neuronal glucose metabolism. The
      resulting decrease in delivery of 14C-glutamate from the neurons to astrocytes
      was probably also the major contributor to the change in 14C-glutamine content.
      These alterations probably result in part from a marked depression of glycolytic
      activity in the neurons, as suggested by previous studies assessing deoxyglucose
      utilization. Alterations in 14C-glucose metabolism were not restricted to tissue
      that would subsequently become infarcted. Thus, these changes did not inevitably
      lead to death of the affected cells. The ATP : ADP ratio and phosphocreatine
      content were essentially preserved during recirculation following 2 h of ischemia
      and showed at most only moderate losses in some subregions following 3 h of
      ischemia. This retention of energy reserves despite the decreases in 14C-glucose
      metabolism in neurons suggests that energy needs were substantially reduced in
      the post-ischemic brain. Marked increases in tissue lactate accumulation during
      recirculation, particularly following 3 h of ischemia, provided evidence that
      impaired pyruvate oxidation probably also contributed to the altered 14C-glucose
      metabolism. These findings indicate the presence of complex changes in energy
      metabolism that are likely to greatly influence the responses of neurons and
      astrocytes to temporary focal ischemia.

PMID- 16606371
TI  - Nitric oxide impairs mitochondrial movement in cortical neurons during hypoxia.
AB  - Cortical nitric oxide (NO) production increases during hypoxia/ischemia in the
      immature brain and is associated with both neurotoxicity and mitochondrial
      dysfunction. Mitochondrial redistribution within the cell is critical to normal
      neuronal function, however, the effects of hypoxia on mitochondrial dynamics are
      not known. This study tested the hypothesis that hypoxia impairs mitochondrial
      movement via NO-mediated pathways. Fluorescently labeled mitochondria were
      studied using time-lapse digital video microscopy in cultured cortical neurons
      exposed either to hypoxia/re-oxygenation or to diethyleneamine/nitric oxide
      adduct, DETA-NO (100-500 microm). Two NO synthase inhibitors, were used to
      determine NO specificity. Mitochondrial mean velocity, the percentage of movement
      (i.e. the time spent moving) and mitochondrial morphology were analyzed. Exposure
      to hypoxia reduced mitochondrial movement to 10.4 +/- 1.3% at 0 h and 7.4 +/-
      1.7% at 1 h of re-oxygenation, versus 25.6 +/- 1.4% in controls (p < 0.05). Mean
      mitochondrial velocity (microm s(-1)) decreased from 0.374 +/- 0.01 in controls
      to 0.146 +/- 0.01 at 0 h and 0.177 +/- 0.02 at 1 h of re-oxygenation (p < 0.001).
      Exposure to DETA-NO resulted in a significant decrease in mean mitochondrial
      velocity at all tested time points. Treatment with NG-nitro-L-arginine methyl
      ester (L-NAME) prevented the hypoxia-induced decrease in mitochondrial movement
      at 0 h (30.1 +/- 1.6%) and at 1 h (26.1 +/- 9%) of re-oxygenation. Exposure to
      either hypoxia/re-oxygenation or NO also resulted in the rapid decrease in
      mitochondrial size. Both hypoxia and NO exposure result in impaired mitochondrial
      movement and morphology in cultured cortical neurons. As the effect of hypoxia on
      mitochondrial movement and morphology can be partially prevented by a nitric
      oxide synthase (NOS) inhibitor, these data suggest that an NO-mediated pathway is
      at least partially involved.

PMID- 16606372
TI  - Inhibition of protein synthesis by activation of NMDA receptors in cultured
      retinal cells: a new mechanism for the regulation of nitric oxide production.
AB  - The synthesis of nitric oxide (NO) is limited by the intracellular availability
      of L-arginine. Here we show that stimulation of NMDA receptors promotes an
      increase of intracellular L-arginine which supports an increase in the production
      of NO. Although L-[3H]arginine uptake measured in cultured chick retina cells
      incubated in the presence of cycloheximide (CHX, a protein synthesis inhibitor)
      was inhibited approximately 75% at equilibrium, quantitative thin-layer
      chromatography analysis showed that free intracellular L-[3H]arginine was six
      times higher in CHX-treated than in control cultures. Extracellular L
      [3H]citrulline levels increased threefold in CHX-treated groups, an effect
      blocked by NG-nitro-L-arginine, a NO synthase (NOS) inhibitor. NMDA promoted a
      40% increase of free intracellular L-[3H]arginine in control cultures, an effect
      blocked by the NMDA antagonist 2-amino 5-phosphonovaleric acid. In parallel, NMDA
      promoted a reduction of 40-50% in the incorporation of 35[S]methionine or L
      [3H]arginine into proteins. Western blot analysis revealed that NMDA stimulates
      the phosphorylation of eukaryotic elongation factor 2 (eEF2, a factor involved in
      protein translation), an effect inhibited by (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine maleate (MK801). In conclusion, we have shown
      that the stimulation of NMDA receptors promotes an inhibition of protein
      synthesis and a consequent increase of an intracellular L-arginine pool available
      for the synthesis of NO. This effect seems to be mediated by activation of eEF2
      kinase, a calcium/calmodulin-dependent enzyme which specifically phosphorylates
      and blocks eEF2. The results raise the possibility that NMDA receptor activation
      stimulates two different calmodulin-dependent enzymes (eEF2 kinase and NOS)
      reinforcing local NO production by increasing precursor availability together
      with NOS catalytic activity.

PMID- 16606373
TI  - Direct evidence for spinal cord microglia in the development of a neuropathic
      pain-like state in mice.
AB  - The present study was undertaken to further investigate the role of glial cells
      in the development of the neuropathic pain-like state induced by sciatic nerve
      ligation in mice. At 7 days after sciatic nerve ligation, the immunoreactivities
      (IRs) of the specific astrocyte marker glial fibrillary acidic protein (GFAP) and
      the specific microglial marker OX-42, but not the specific oligodendrocyte marker
      O4, were increased on the ipsilateral side of the spinal cord dorsal horn in
      nerve-ligated mice compared with that on the contralateral side. Furthermore, a
      single intrathecal injection of activated spinal cord microglia, but not
      astrocytes, caused thermal hyperalgesia in naive mice. Furthermore, 5-bromo-2'
      deoxyuridine (BrdU)-positive cells on the ipsilateral dorsal horn of the spinal
      cord were significantly increased at 7 days after nerve ligation and were highly
      co-localized with another microglia marker, ionized calcium-binding adaptor
      molecule 1 (Iba1), but neither with GFAP nor a specific neural nuclei marker,
      NeuN, in the spinal dorsal horn of nerve-ligated mice. The present data strongly
      support the idea that spinal cord astrocytes and microglia are activated under
      the neuropathic pain-like state, and that the proliferated and activated
      microglia directly contribute to the development of a neuropathic pain-like state
      in mice.

PMID- 16606374
TI  - An unusual cause of chronic cough. Foreign body aspiration.
AB  - Foreign body aspiration (FBA) is a serious medical problem, causing thousands of
      deaths nationally each year. Clinical presentations range from acute suffocation
      and death to chronic and subtle respiratory symptoms. Although FBA is more common
      in children, adult patients are also at risk. We present a classic case of FBA in
      an adult male with a history of alcohol abuse and chronic cough.

PMID- 16606376
TI  - Abdominal pain from a thoracic epidural abscess.
AB  - Spinal epidural abscesses are difficult to diagnose and are associated with high
      morbidity and mortality. A 61-year-old Chinese woman fell and was admitted 5 days
      later with constant epigastric pain and constipation. Clinical examination was
      initially normal. Five days after admission, she developed urinary retention and
      mild lower limb weakness, progressing overnight to paraplegia. Clinical
      examination was consistent with a thoracic myelopathy. Neuroimaging showed a
      paracentral fluid collection compressing the thoracic cord at T8 level. Emergent
      neurosurgical intervention revealed an epidural abscess, which was drained. She
      responded to a 9-week course of antibiotics and recovered fully. Radicular pain
      from thoracic pathology can mimic intraabdominal pathology, and a high index of
      suspicion and prompt surgical intervention are essential to avoid the potentially
      devastating consequences of delayed recognition of epidural abscesses.

PMID- 16606375
TI  - Worsening of asthma with systemic corticosteroids. A case report and review of
      literature.
AB  - Despite widespread use for treatment of asthma and allergies, glucocorticoids may
      cause allergic reactions, even anaphylaxis. The incidence of adverse reactions to
      systemic glucocorticoids is 0.3%. The most commonly reported corticosteroids
      causing anaphylaxis like reactions are hydrocortisone, prednisone, and
      methylprednisolone. Most authors agree that allergic reactions to systemic
      corticosteroids are possibly immunoglobulin E mediated. We report a patient with
      asthma, aspirin allergy, and nasal polyps who developed bronchospasm following
      the administration of intravenous methylprednisolone sodium succinate during an
      acute asthmatic attack. We discuss the differential diagnosis of worsening asthma
      despite adequate treatment, and suggest corticosteroid-induced bronchospasm in
      our patient. Corticosteroid-induced bronchospasm should be considered when
      asthmatics fail to improve, or frankly deteriorate with systemic corticosteroid
      therapy, particularly when a history of aspirin allergy is present. TEACHING
      POINT: Know the differential diagnosis for worsening of asthma despite adequate
      treatment. Consider corticosteroid-induced bronchospasm when asthmatics fail to
      improve, or frankly deteriorate with systemic corticosteroid therapy.
      Corticosteroid-induced bronchospasm is more commonly seen in asthmatics with a
      history of aspirin allergy.

PMID- 16606377
TI  - Association of postoperative complications with hospital costs and length of stay
      in a tertiary care center.
AB  - BACKGROUND: Postoperative complications are a significant source of morbidity and
      mortality. There are limited studies, however, assessing the impact of common
      postoperative complications on health care resource utilization. OBJECTIVE: To
      assess the association of clinically important postoperative complications with
      total hospital costs and length of stay (LOS) in patients undergoing noncardiac
      surgery. METHODS: We determined total hospital costs and LOS in all patients
      admitted to a single tertiary care center between July 1, 1996 and March 31, 1998
      using a detailed administrative hospital discharge database. Total hospital costs
      and LOS were adjusted for preoperative and surgical characteristics. RESULTS: Of
      7,457 patients who underwent noncardiac surgery, 6.9% developed at least 1 of the
      postoperative complications. These complications increased hospital costs by 78%
      (95% confidence interval [CI]: 68% to 90%) and LOS by 114% (95% CI: 100% to 130%)
      after adjustment for patient preoperative and surgical characteristics.
      Postoperative pneumonia was the most common complication (3%) and was associated
      with a 55% increase in hospital costs (95% CI: 42% to 69%) and an 89% increase in
      LOS (95% CI: 70% to 109%). CONCLUSIONS: Postoperative complications consume
      considerable health care resources. Initiatives targeting prevention of these
      events could significantly reduce overall costs of care and improve patient
      quality of care.

PMID- 16606378
TI  - Brief report: Influenza vaccination and health care workers in the United States.
AB  - OBJECTIVE: To determine influenza vaccination rates among U.S. health care
      workers (HCWs) by demographic and occupational categories. DESIGN AND
      PARTICIPANTS: We analyzed data from the 2000 National Health Interview Survey
      (NHIS). Weighted multivariable analyses were used to evaluate the association
      between HCW occupation and other variables potentially related to receipt of
      influenza vaccination. HCWs were categorized based on standard occupational
      classifications as health-diagnosing professions, health-assessing professions,
      health aides, health technicians; or health administrators. MAIN INDEPENDENT
      VARIABLES: Demographic characteristics and occupation category. MAIN OUTCOME
      VARIABLES: Receipt of influenza vaccination within 12 months of survey. ANALYSIS:
      Descriptive statistics and weighted multivariable logistic regression. RESULTS:
      There were 1,651 HCWs in the final sample. The overall influenza vaccination rate
      for HCWs was 38%. After weighted multivariable analyses, HCWs who were under 50
      (odds ratio [OR] 0.67%, 95% confidence interval [CI]: 0.50 to 0.89, compared with
      HCWs 50 to 64), black (OR 0.57 95% CI: 0.42, 0.78, compared with white HCWs), or
      were health aides (OR 0.73%, 95% CI: 0.51, 1.04, compared with health care
      administrators and administrative support staff) had lower odds of having been
      vaccinated against influenza. CONCLUSIONS: The overall influenza vaccination rate
      among HCWs in the United States is low. Workers who are under 50, black, or
      health aides have the lowest rates of vaccinations. Interventions seeking to
      improve HCW vaccination rates may need to target these specific subgroups.

PMID- 16606379
TI  - Brief report: Failure of an electronic medical record tool to improve pain
      assessment documentation.
AB  - OBJECTIVE: To comply with pain management standards, Bellevue Hospital in New
      York City implemented a mandatory computerized pain assessment screen (PAS) in
      its electronic medical record (EMR) system for every outpatient encounter. We
      assessed provider acceptance of the instrument and examined whether the
      intervention led to increased documentation of pain-related diagnoses or
      inquiries. DESIGN: Cross-sectional survey; a pre- and posthistorically controlled
      observational study. SUBJECTS AND MEASUREMENTS: The utility of the computerized
      tool to medicine housestaff and attendings was assessed by an anonymous survey.
      We conducted an electronic chart review comparing all adult primary care patient
      encounters over a 2-day period 6 months prior to implementation of the PAS and on
      2 days 6 months after its implementation. RESULTS: Forty-seven percent of survey
      respondents felt that the computerized assessment tool was "somewhat difficult"
      or "very difficult" to use. The majority of respondents (79%) felt the tool did
      not change their pain assessment practice. Of 265 preintervention patients and
      364 postintervention patients seen in the clinic, 42% and 37% had pain-related
      diagnoses, respectively (P=.29). Pain inquiry by the physician was noted for 49%
      of preintervention patients and 44% of the postintervention patients (P=.26). In
      55% of postintervention encounters, there was discordance between the pain
      documentation using the PAS tool and the free text section of the medical note.
      CONCLUSION: A mandatory computerized pain assessment tool did not lead to an
      increase in pain-related diagnoses and may have hindered the documentation of
      pain assessment because of the perceived burden of using the application.

PMID- 16606384
TI  - Computer-assisted technology: not if, not when, but how. A systematic review of
      interactive computer-assisted technology in diabetes care.

PMID- 16606385
TI  - The relevance of cultural distance between patients and physicians to racial
      disparities in health care.

PMID- 16606386
TI  - Primary prevention of heart failure in cardiac pacing.

PMID- 16606387
TI  - Assessment of atrial regional wall motion using strain Doppler imaging during
      biatrial pacing in the bradycardia-tachycardia syndrome.
AB  - INTRODUCTION: Biatrial pacing is expected to have preventive effects on atrial
      fibrillation. METHODS: We evaluated atrial regional wall motion by strain Doppler
      imaging (SDI) in 6 patients (62.5 +/- 11.3 [SD] years), who suffered from atrial
      fibrillation, with an implanted biatrial pacemaker. SDI was performed and atrial
      regional wall motion was estimated during biatrial (BiA) and right atrial
      appendage (RAA) pacing. RESULTS: There was no significant difference in the
      interval from the pacing spike to the peak strain of the atrium in the lateral
      right atrium (LRA) between BiA and RAA pacing. However, there was a significant
      difference in the septal atrium (SA) between BiA and RAA pacing (225.0 +/- 19.9
      vs 267.2 +/- 15.7 ms, P < 0.0001) and in the lateral left atrium (LLA) between
      BiA and RAA pacing (216.7 +/- 21.6 vs 275.0 +/- 16.2 ms, P < 0.0001). There were
      significant differences in the time difference of peak strain between BiA and RAA
      pacing in each atrial segment (LRA-AS: 2.2 +/- 5.9 vs 45.0 +/- 11.9 ms, P =
      0.0016, SA-LLA: -8.3 +/- 5.5 vs 7.8 +/- 2.7 ms, P < 0.0011, LRA-LLA: -6.1 +/- 3.9
      vs 52.8 +/- 13.2 ms, P = 0.0002). There was no significant difference in the
      interval from the pacing spike to the inflection point of atrial strain (S-I) of
      LRA. However, there were significant differences in S-I of SA (83.9 +/- 24.1 vs
      129.9 +/- 30.6 ms, P = 0.0086) and LLA (102.2 +/- 37.9 vs 166.1 +/- 13.4 ms, P =
      0.0028). CONCLUSION: BiA pacing improved the synchronicity of regional wall
      motion of both atrium.

PMID- 16606388
TI  - Long-term performance of active-fixation pacing leads: a prospective study.
AB  - BACKGROUND: Despite the increasingly widespread use of active-fixation leads,
      long-term clinical follow-up of pacing lead outcomes is lacking. The aim was to
      analyze pacing parameters over a 2-year follow-up. We performed a prospective
      observational study of consecutive new pacemaker implants using the 1488T St.
      Jude (100) and the Medtronic 5076 (100) active-fixation leads. Detailed analysis
      of pacing parameters was collected at implant, day 1, and 1, 3, 6, 12, 18, and 24
      months. METHODS AND RESULTS: One hundred patients underwent implantation of 100
      dual-chamber pacemakers. Initial pacing parameters in the ventricle were
      threshold 0.7 +/- 0.2 V, R wave 12.0 +/- 6.5 mV, and impedance 879 +/- 224 Omega.
      Threshold increased significantly from day 1 (0.7 +/- 0.2 V) to month 1 (0.9 +/-
      0.6 V, P < 0.01) and remained stable over the long term. Four of the 100 patients
      had a threshold >2 V (mean 3.3 +/- 0.9 V) all between day 1 and month 3. For all
      patients, R wave remained stable, but impedance declined significantly from day 1
      (879 +/- 184 Omega) to month 1 (677 +/- 122 Omega, P < 0.01). There were no
      ventricular lead complications. Initial pacing parameters in the atrium were
      threshold 0.9 +/- 0.3 V, P wave 3.3 +/- 2.4 mV, and impedance 606 +/- 144 Omega.
      Threshold remained stable over the long-term follow-up. One of 100 patients had a
      rise in threshold >2 V (2.2 V) between day 1 and month 1. No patients underwent
      lead repositioning. Sensing and impedance remained stable over the long term.
      Patient follow-up was completed in 94% (6 unrelated deaths). There was an 8%
      incidence of atrial fibrillation. CONCLUSION: Active-fixation leads are generally
      associated with stable long-term pacing parameters.

PMID- 16606389
TI  - Transvenous pacemaker lead removal is safe and effective even in large
      vegetations: an analysis of 53 cases of pacemaker lead endocarditis.
AB  - BACKGROUND: The aim of this study was to investigate whether transvenous lead
      removal is safe and effective in patients with lead vegetations greater than 1 cm
      in size. METHODS: From 1991 to 2005, a total of 53 patients underwent pacemaker
      or ICD lead removal for vegetations. Transvenous lead removal using locking
      stylets and sheaths was performed in 30 patients (56.6%) and was found to be
      effective in 29 of those patients. In 1 patient, due to rupture of the lead, open
      heart removal of the ventricular lead remnant and tricuspid valve repair had to
      be performed due to persistent infection. In 23 of these patients,
      transesophageal echocardiography (TEE) verified vegetations greater than 1 cm in
      size. The remaining patients underwent primary lead removal using sternotomy and
      extracorporeal circulation (ECC). Pacemaker pocket infection was found in 16
      patients (55.2%) of the transvenous study group and in 11 patients (45.8%) of the
      ECC group (P = 0.72). RESULTS: Perioperative mortality was 5.7% (3 patients); all
      of them underwent primary ECC removal and had severe endocarditis of the
      tricuspid valve. None of the patients who underwent transvenous lead removal died
      and there were no further complications such as pericardial tamponade or major
      pulmonary embolism requiring further interventions, even in patients
      demonstrating large vegetations. CONCLUSIONS: This study demonstrates that
      transvenous lead removal is a safe and highly effective procedure for the removal
      of infected pacemaker and ICD leads, even in patients with large vegetations.
      Embolism to the lung proceeds mainly without further complications; however,
      patients with vegetations that might obstruct a main stem of the pulmonary artery
      should undergo ECC removal.

PMID- 16606390
TI  - Reduction of right ventricular pacing in patients with dual-chamber ICDs.
AB  - BACKGROUND: Unnecessary right ventricular (RV) pacing in patients with
      implantable cardioverter defibrillators (ICD) may adversely affect heart failure
      morbidity and total mortality. Inhibition of Unnecessary RV Pacing with AV Search
      Hysteresis in ICDs (INTRINSIC RV) is a prospective, multicenter, randomized trial
      evaluating outcomes in ICD recipients programmed to single-chamber pacing (VVI)
      versus dual-chamber (DDDR) pacing with AV search hysteresis (AVSH). METHODS:
      Patients underwent ICD implant (for standard indications). The ICD was programmed
      to DDDR with AVSH regardless of any need for pacing. Rate-adaptive pacing was set
      at 60-130 ppm with dynamic AV delay from 200 to 90 ms. AVSH was programmed to
      search every 32 intervals and extend the AV delay by 50%. One week post-implant
      patients with ICDs were interrogated to assess the percentage of RV pacing with
      the expectation that most would have <20% RV pacing and would be randomized into
      INTRINSIC RV. Early analysis showed that targets for randomization were not met.
      AVSH parameters were modified under a protocol amendment to increase AV delay
      extension to 100%. We report findings related to this programming change based
      upon analyses of (nonrandomized) data pre- and post-amendment. RESULTS: Twenty
      one percent of patients (n = 314) were enrolled pre-amendment and 79% (n = 1,216)
      were enrolled post-amendment. The mean percentage of RV pacing at the 1-week
      visit was 41.4 +/- 29.6% pre-amendment and 14.7 +/- 22.6% post-amendment (P <
      0.0001). The proportion of patients eligible for randomization (RV pacing <20% at
      the 1-week visit) was 31.2% pre-amendment and 76.8% post-amendment (P < 0.0001).
      CONCLUSION: AVSH can dramatically reduce the percentage of RV pacing among ICD
      recipients.

PMID- 16606391
TI  - Continuous template collection and updating for electrogram morphology
      discrimination in implantable cardioverter defibrillators.
AB  - INTRODUCTION: Electrogram morphology analysis improves discrimination of
      supraventricular tachycardias (SVTs) from ventricular tachycardias (VTs) in
      implantable cardioverter defibrillators (ICDs), but electrogram morphology may
      change with lead maturation, drugs, or disease progression. We report the
      clinical performance of an automatic algorithm that creates and updates templates
      from non-paced, slow rhythm and continuously checks the quality of the template
      used for arrhythmia discrimination. METHODS AND RESULTS: We studied this
      algorithm in 193 patients with single-chamber ICDs (Marquis VR, Medtronic Inc.,
      Minneapolis, MN, USA). Of the 112 patients who completed 6-month follow-up, 99.1%
      of the patients had > or =1 automatic template created. Match scores between
      template and ongoing rhythm are computed using Haar Wavelets. Of the 435
      automatic templates evaluated at follow-up, 423 (97.2%) had a median match score
      > or =70%. Intrinsic rhythm at 1 month had significantly higher match scores (P <
      0.001) with automatic templates (90.3 +/- 7.0%) than with manual templates (85.7
      +/- 10.9%) generated at pre-hospital discharge (PHD). The percentage of
      appropriately rejected SVTs was slightly higher with the automatic template
      (280/339 episodes) than with the manual template at PHD (272/339 episodes) while
      the Wavelet detection of VT was the same (218/220 episodes). CONCLUSIONS: In
      patients receiving ICDs, the automatic templates were successfully created during
      a 6-month follow-up period, and consistently matched the patients' intrinsic
      rhythm at the nominal match threshold. Both early (<1 month postimplant) and late
      (1- to 3-month follow-up period) changes in electrogram morphology were
      identified, confirming the need for automatic template updating.

PMID- 16606392
TI  - Antiinflammatory effects of cardiac resynchronization therapy in patients with
      chronic heart failure.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) pacing has been proposed as
      an additional treatment to medical therapy to improve heart failure patients with
      left ventricular asynchrony. The aim of this study was to evaluate the influence
      of CRT treatment on proinflammatory cytokines in patients with heart failure.
      METHODS: Twenty patients, with a mean age 64 +/- 2 years, with severe chronic
      heart failure NYHA class II-IV (mean ejection fraction 25 +/- 2%), were included
      in the study. Patients were treated with CRT pacing, after failure of optimal
      therapy. Blood samples were taken at baseline, 3 months after pacing therapy, and
      after a subsequent 3-month period of no pacing for the assessment of
      proinflammatory cytokines TNF-alpha and its receptors (sTNFR-I, sTNFR-II), IL-6,
      adhesion molecules sICAM-1 and sVCAM-1, and the apoptotic indices sFas and sFas
      Ligand. RESULTS: Levels of TNF-alpha, sTNFR-I, and sTNFR-II were reduced at the
      end of 3 months of CRT therapy and further reduced at the end of the no pacing
      period (P < 0.05, compared to baseline). Levels of IL-6 also declined after 3
      months of CRT pacing (from 8.9 +/- 2.5 pg/mL to 4.7 +/- 1.3 pg/mL, P < 0.05) and
      this was maintained during the no pacing period (3.9 +/- 1.1 pg/mL P < 0.05
      compared to baseline). The adhesion molecule sICAM-1 levels also reduced (from
      265 +/- 17 ng/mL to 235 +/- 12, P < 0.05) after 3 months of CRT pacing and
      remained unchanged at the end of the no pacing period (219 +/- 12 ng/mL, P < 0.05
      compared to baseline values). CONCLUSION: Major proinflammatory cytokines and the
      adhesion molecule sICAM-1 are reduced with CRT therapy and this effect is
      maintained for at least 3 months after discontinuation of pacing.

PMID- 16606393
TI  - X-ray dose reduction in fluoroscopically guided electrophysiology procedures.
AB  - This study assessed the efficacy of a new dose reduction regime in
      fluoroscopically guided electrophysiology (EP) procedures, which included
      diagnostic electrophysiological investigations, radiofrequency ablation, and
      biventricular pacing. A modified dose regime for fluoroscopy was implemented in
      one of our cardiac electrophysiology laboratories. The x-ray system was
      programmed with a hierarchy of three fluoroscopy doses, and therefore image
      quality and settings. The default (lowest) dose mode was not expected to be
      suitable for all patient sizes or for the entirety of all procedures. Staff
      raised the dose level in a stepped manner as and when required to optimize the
      imaging requirements of the procedure. Phantom studies indicated that the low
      dose mode provided adequate image quality for visualizing EP catheters, while
      significantly lowering patient skin dose. In 52 clinical cases, questionnaires
      were used to assess the subjective clinical image quality. The mean image quality
      score for the low dose setting was rated between "adequate" and "good." The
      fluoroscopy dose level was raised from the lowest level for 6% of the total
      fluoroscopy time. Procedural Dose Area Product (DAP) meter readings were analyzed
      for patients prior to (n = 85) and after (n = 150) the implementation of the low
      dose regime and showed an overall reduction in DAP rate of 74%. The hierarchical
      dose regime proved to be acceptable in routine clinical practice for EP
      procedures, leading to significant reductions in patient doses.

PMID- 16606394
TI  - Simple diagnosis of limb-lead reversals by predictable changes in QRS axis.
AB  - BACKGROUND: Limb-lead reversals (LLRs) remain clinically problematic. Because the
      frontal QRS axis is derived from an equilateral Einthoven triangle and LLRs
      either rotate (180 degrees horizontally (mirror-image (M)) and/or 120 degrees
      vertically (clockwise (C)/counterclockwise (CC)) or distort the triangle (by
      forcing a bipolar lead to record across the lower extremities (LE) where
      electrical potentials approach zero (zero-potential lead)), we hypothesize that
      LLR axes changes from a baseline value (n) are predictable. METHODS: Three
      hundred and sixty ECGs with all 24 limb-lead combinations from 15 individuals
      were analyzed. Predicted and actual QRS axes were compared using linear
      regression. RESULTS: Twenty-four lead combinations produced only 12 (11 abnormal)
      ECG patterns and diagnosis depended upon identifying upper extremity (UE) cable
      configurations. Predicted formulas for rotation-type LLR axes (M, C, CC, MC, and
      MCC) were 180 - n, n - 120, n + 120, 300 - n, and 60 - n, respectively.
      Corresponding mean differences between predicted and actual values were 4 +/- 5
      degrees , 4 +/- 2 degrees , 7 +/- 10 degrees , 5 +/- 7 degrees , and 3 +/- 4
      degrees (all r = 0.99 - 1.00, P < 0.0001). The predicted formula for distortion
      type LLR axes is (zero-potential lead axis) +/- 90 degrees . Actual mean values
      for zero-potential lead I, II, and III were 90 +/- 7 degrees or 266 +/- 17
      degrees , -31 +/- 6 degrees or 148 +/- 14 degrees , and 26 +/- 14 degrees or 209
      +/- 9 degrees , respectively. The mean difference between predicted and actual
      values for all LLRs was 5 +/- 8 degrees (r = 1.00, P < 0.0001). CONCLUSIONS: LLR
      axes are predictable within an average of 5 degrees . This might help
      differentiate an acute axis shift due to an LLR from serious medical conditions
      that may require treatment.

PMID- 16606395
TI  - Comparison of the healing mechanisms of myocardial lesions induced by dry
      radiofrequency and microwave epicardial ablation.
AB  - BACKGROUND: Histological assessment of the evolution of lesions induced on a
      pig's left atrium by microwave (MW) epicardial applications and comparison with
      dry radiofrequency (RF) lesions. METHODS: MW (40 W, 40 seconds) and dry RF (80
      degrees C, 2 minutes) were epicardially applied on nine pigs' left atrium.
      Samples were procured following application (n = 2), at day 3 (n = 2), day 7 (n =
      2), day 14 (n = 2), and at 1 month (n = 1). They were fixed in formalin, embedded
      in paraffin, sectioned (2 mu), stained with histochemical dyes, immunomarked, and
      histologically analyzed. RESULTS: Histological features of acute stage MW lesion
      are interstitial hemorrhage, adipose, and muscular tissues' coagulation necrosis,
      thrombosis of myocardial interstitium small vessels at damaged and optically
      undamaged areas, epicardial coronary branches, and endocardial parietal
      thrombosis. Day 3-lymphohistiocytic infiltration (lysosyme+) highlights lesion
      limits. Day 7-lymphohistiocytic infiltration increases, multi-nucleated giant
      cells appear surrounding/fagocyting necrotic tissue. Neovessels and scarce
      myofibroblasts appear. Lesion edges are now better defined. Day 14
      myofibroblastic proliferation (actin++, vimentin+) creates "young" scar tissue,
      as in "healing by second intention." Lesions are deeper and wider than appeared
      at acute stage. One month-dense fibrous tissue scar appears. Endothelial cells
      covering endocardium are morphologically intact. RF lesions are histologically
      identical to MW's, although no vessel thrombosis was identified at acute
      optically undamaged areas and cytomorphologic elements emerge at later stages in
      the healing process. CONCLUSIONS: (1) Microwave scars are deeper and wider than
      the lesions observed at the acute stage. (2) Evolution of microwave lesions is
      faster and induces broader scars than dry radiofrequency. (3) Scar formation
      (both energies) is "healing by second intention." (4) Endocardial thrombosis may
      occur despite morphologically intact endothelium.

PMID- 16606396
TI  - Atrial linear lesions: feasibility using cryoablation.
AB  - BACKGROUND: Long linear lesions are created in the left atrium to modify the
      atrial substrate, thereby curing atrial fibrillation. The creation of long linear
      left atrial lesions using radiofrequency (RF) ablation is time consuming and
      difficult. Furthermore, it might result in significant complications.
      Cryoablation might overcome some of the disadvantages of RF ablation. Therefore,
      the aim of our study was to assess whether the creation of a long linear lesion
      is possible using cryotherapy. METHODS: A right atrial septal linear lesion was
      created in six pigs (median weight: 50 kg; range: 40-60 kg). The ablation
      procedure was performed with a 7-F Freezor cryocatheter. The nonfluoroscopic
      mapping system LocaLisa was used as a navigation tool. At each point, freezing
      was maintained at the lowest attainable temperature (-75 degrees C) for 4
      minutes. The CARTO system was used for the evaluation of the linear lesions.
      Furthermore, all animals were sacrificed immediately after the ablation procedure
      and a postmortem examination of the lesions was performed. Additionally, an
      analysis of the amplitudes of the intracardiac electrograms registered via the
      ablation catheter was performed before and after the ablation procedure. RESULTS:
      A right atrial septal linear lesion could be created successfully in all six
      pigs. For the performance of this ablation line, a median number of 16
      cryoapplications (range, 11-26) was necessary. The amplitudes of the intracardiac
      electrograms registered via the ablation catheter decreased significantly after
      ablation. The CARTO bipolar voltage map revealed very low potentials along the
      ablation line and showed a sharply demarcated ablation area at the septum in all
      pigs. Further analysis of the CARTO map revealed an incomplete conduction block
      in all cases. Most of the pigs had a small gap close to the fossa ovalis. The
      postmortem examination of 2,3,5-triphenyl-tetrazolium chloride-stained specimens
      showed sharply demarcated lesions without any ulcerations. There were no major
      complications during the procedure. CONCLUSIONS: The creation of long linear
      lesions using cryoablation is feasible and safe. Lesion characteristics are
      different and more favorable than those created by RF. However, the aim of
      creating a transmural lesion and a complete conduction block remains an unsolved
      problem even with current cryoablation techniques. Nevertheless, growing
      experience and technical improvements might overcome some of the current
      limitations of this new technique.

PMID- 16606397
TI  - Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial
      fibrillation.
AB  - Early (EAD) and delayed (DAD) afterdepolarizations-induced triggered activity is
      capable of initiating and maintaining cardiac arrhythmias. EAD-induced triggered
      responses are traditionally thought to be involved in the generation of
      ventricular arrhythmias under long QT conditions and are precipitated by
      bradycardia or long pauses. In contrast, DAD-induced triggered activity commonly
      underlies arrhythmias precipitated by tachycardia. Spontaneous release of calcium
      from the sarcoplasmic reticulum (SR) secondary to cellular calcium overload
      induces DADs and some forms of EADs. Recent studies from our laboratory have
      uncovered a novel mechanism giving rise to triggered activity, termed "late-phase
      3 EAD," which combines properties of both EAD and DAD, but has its own unique
      character. Late-phase 3 EAD-induced triggered extrasystoles represent a new
      concept of arrhythmogenesis in which abbreviated repolarization permits "normal
      SR calcium release" to induce an EAD-mediated closely coupled triggered response,
      particularly under conditions permitting intracellular calcium loading. This
      review briefly describes the mechanisms and properties of late-phase 3 EADs, how
      they differ from conventional EADs and DADs, as well as their role in the
      initiation of cardiac arrhythmias, such as atrial fibrillation.

PMID- 16606398
TI  - Wide QRS complex tachycardia in a patient with a minute ventilation rate
      responsive pacemaker.

PMID- 16606399
TI  - The deleterious consequences of right ventricular apical pacing: time to seek
      alternate site pacing.
AB  - BACKGROUND: The purpose of this article is to critically review the data
      accumulated to date from studies evaluating the hemodynamic and clinical effects
      of right ventricular apical pacing during conventional permanent cardiac pacing.
      The data from studies comparing the effects of right ventricular apical pacing
      and alternate site ventricular pacing are also reviewed. METHODS: We conducted a
      MEDLINE and journal search of English-language reports published in the last
      decade and searched relevant papers. RESULTS: Although intraventricular
      conduction delay in the form of left bundle branch block (LBBB) has traditionally
      been viewed as an electrophysiologic abnormality, it has now become abundantly
      clear that it has profound hemodynamic effects due to ventricular dyssynchrony,
      especially in patients with heart failure. These deleterious effects can be
      significantly ameliorated by cardiac resynchronization therapy effected by
      biventricular or left ventricular pacing. However, not only is spontaneous LBBB
      harmful, but the iatrogenic variety produced by right ventricular apical pacing
      in patients with permanent pacemakers may be equally deleterious. In this review
      new evidence from recent studies is presented, which strongly suggests a harmful
      effect of our long-standing practice of producing an iatrogenic LBBB by
      conventional right ventricular apical pacing in patients receiving permanent
      pacemakers. This emerging strong new evidence about the adverse hemodynamic and
      clinical effects of right ventricular apical pacing would dictate a reassessment
      of our traditional approach to permanent cardiac pacing and direct our attention
      to alternate sites of pacing, such as the left ventricle and/or the right
      ventricular outflow tract or septum, if not for all patients, at least for those
      with left ventricular dysfunction. Indeed, current convincing data on alternate
      site ventricular pacing are encouraging and this approach should be actively
      pursued and further investigated in future studies. CONCLUSIONS: Not only is
      spontaneous permanent LBBB harmful to our patients, but the iatrogenic variety
      produced by right ventricular apical pacing during conventional permanent pacing
      may also be deleterious to some patients. The compelling evidence presented
      herein cannot be ignored; it may dictate a change of attitude toward right
      ventricular apical pacing directing our attention to alternate sites of
      ventricular pacing and avoidance of the right ventricular apex.

PMID- 16606400
TI  - A death in Venice.

PMID- 16606401
TI  - Syncopal high-degree AV block treated with catheter RF ablation without pacemaker
      implantation.
AB  - A 23-year-old-female patient had undergone a very successful gastric banding
      surgery to treat obesity. Six months later she began to present recurrent syncope
      due to very frequent, intermittent high-degree AV block referred to as pacemaker
      implantation. The electrophysiological study showed impaired AV nodal conduction
      but the His-Purkinje conduction was preserved. Partial catheter radiofrequency
      ablation of the cardiac autonomic nervous system guided by spectral endocardial
      mapping (cardioneuroablation) was performed. The electrophysiological parameters
      were normalized. Holter recordings were normal and the patient was asymptomatic
      with normal life without pacemaker implantation in a follow-up 21 months later.

PMID- 16606402
TI  - Inducible atrioventricular nodal reentrant echo behind organic 2:1 infra-hisian
      block during sinus rhythm.
AB  - A 77-year-old male patient with an intermittent 2:1 infra-Hisian block during
      sinus rhythm was presented with dizziness and near-syncope. During
      electrophysiological (EP) study, dual atrioventricular (AV) nodal pathways and
      retrograde fast pathway were easily induced by atrial and ventricular programmed
      stimulation, respectively. A typical slow-fast AV nodal reentrant echo beat also
      could be demonstrated by single atrial extrastimulation. Atrioventricular nodal
      reentrant tachycardia (AVNRT) can occasionally exhibit 2:1 AV block. Conversely,
      AV nodal reentry property had been rarely reported behind 2:1 infra-Hisian block.
      The EP presentation from this case may support the notion that tissues below the
      His are not part of the reentrant circuit of AVNRT.

PMID- 16606403
TI  - Monomorphic ventricular tachycardia induced by cardiac resynchronization therapy
      in patient with severe nonischemic dilated cardiomyopathy.
AB  - We report the case of a patient with severe nonischemic dilated cardiomyopathy in
      whom cardiac resynchronization therapy (CRT) was the source of incessant, drug
      resistant, monomorphic ventricular tachycardia (VT). VT recurrences were only
      resolutive with inactivation of CRT and reactivation of CRT reproduced VT
      occurrence. The possible pathophysiology of the VT and the potential ventricular
      proarrhythmic risk related to CRT are discussed. This report points out clearly
      that CRT can induce ventricular arrhythmias and suggests the need for CRT
      systematically associated with a defibrillation system.

PMID- 16606404
TI  - Cavotricuspid isthmus catheter ablation across an inferior vena cava filter.
AB  - Patients who suffer from recurrent thromboembolic events often receive an
      inferior vena cava (IVC) filter. There are few data available regarding treatment
      of this patient population with catheterization interventions, especially
      catheter ablation. We report a case of cavotricuspid isthmus catheter ablation
      across an IVC filter.

PMID- 16606405
TI  - A biventricular ICD system with biventricular defibrillation.
AB  - We describe the case of a 59-year-old gentleman with severe dilated
      cardiomyopathy requiring implantation of a dual-chamber biventricular implantable
      cardioverter-defibrillator (ICD). High defibrillation thresholds (DFT) were
      encountered at implant with an inadequate defibrillation safety margin. Testing
      of all possible shock vectors/polarities with and without the SVC coil and
      optimization of the distal RV coil position all proved inadequate. A satisfactory
      defibrillation safety margin was achieved following placement of a second lead in
      the coronary sinus to enable biventricular defibrillation. This case highlights
      an additional strategy for combating high DFTs and is an option even in dual
      chamber biventricular ICD systems.

PMID- 16606407
TI  - Right ventricular anodal capture during left ventricular stimulation in CRT
      implantable cardioverter defibrillators (ICD).

PMID- 16606409
TI  - Association of HLA subtype DRB10407 in Colombian patients with actinic prurigo.
AB  - BACKGROUND: Human leukocyte antigen (HLA) DRB1*0407 had been associated with
      actinic prurigo in different populations. This class II HLA-DR subtype had not
      been studied in Colombia. OBJECTIVE: The objective of this study was to establish
      whether there was an association of actinic prurigo with HLA DR in a Colombian
      population. MATERIALS AND METHODS: Forty patients with a clinical diagnosis of
      actinic prurigo and 40 healthy subjects, paired by age, sex and birthplace, were
      studied. HLA typing for HLA DRB1 and DRB1*04, if necessary, was performed by the
      PCR-SSP method using blood samples. RESULTS: A high frequency of HLA DRB1*0407
      was found in the patients (97.5% vs. 30%; P<0.00001). The allelic frequency of
      HLA DRB1*0407 was 63.8% in the case group, and 14.5% in the controls (P<0.00001).
      In the control group, there was a higher frequency of the alleles DRB1*01 (14.5%
      vs. 1.25%; P=0.0027) and DRB1*13 (23.7% vs. 2.5%; P=0.00013). LIMITATIONS: The
      small number of controls does not allow us to drive conclusions about other HLA
      alleles. CONCLUSIONS: HLA subtype DRB1*0407, found in actinic prurigo patients in
      studies conducted in England, Scotland, Ireland and Mexico, was also associated
      in Colombian patients. This finding, concordant in patients from different ethnic
      groups, could be helpful in the diagnosis of this disease and probably important
      in its pathogenesis. DRB1*01 and DRB1*13 alleles were more frequent in controls
      than in patients; we do not know whether they play any role in the resistance to
      the disease.

PMID- 16606410
TI  - Reduction of the UV burden to indoor tanners through new exposure schedules: a
      pilot study.
AB  - BACKGROUND: The development of new pigmentation (tan) in human skin after UV
      exposure requires several days. Once it is developed, the tan can last for weeks.
      Current recommendations for tanning exposure schedules in the USA (FDA Letter to
      Manufacturers: Policy on maximum timer interval and exposure schedule for
      sunlamps, August 21, 1986) allow exposures three times per week for the
      development of a tan, and one to two times per week for maintenance exposures.
      However, this policy is often interpreted in the indoor tanning industry as
      allowing three exposures per week on a continuous basis. We believe that the
      reduction of the recommended cumulative dose to indoor tanners should be
      explored. Two approaches for achieving this are (1) decreasing the number of
      exposures and (2) increasing the time interval between exposures. To explore such
      changes, we conducted a pilot study. METHODS: The pilot study involved three
      exposure schedules (evaluated on each of six subjects) that evolved throughout
      the course of the study. Digital photography, visual assessment and diffuse
      reflectance spectrometry were used to assess skin color changes. The six pilot
      subjects were studied for 8-18 weeks. The changes in skin color obtained through
      the use of the different exposure schedules were compared with changes reported
      by Caswell (Caswell M, The kinetics of the tanning response to tanning bed
      exposures, Photodermatol Photoimmunol Photomed 2000: 16: 10-14) who used
      schedules based on current recommendations. RESULTS: Two out of the three
      experimental schedules produced tans comparable with those reported by Caswell.
      In these two schedules, cumulative doses were a factor of 2-3 below doses from
      current schedules. CONCLUSION: The UV burden to indoor tanners can be
      substantially reduced without compromising the cosmetic effect. These results
      need to be confirmed in a larger study.

PMID- 16606411
TI  - Biological effects of simulated ultraviolet daylight: a new approach to
      investigate daily photoprotection.
AB  - BACKGROUND: The irradiance of standard ultraviolet daylight (UV-DL) is
      representative of most frequently encountered UV exposure conditions and
      simulators of UV-DL can now be used to properly investigate the biological
      effects of a non-extreme UV radiation. One of the characteristics of the
      simulated UV-DL used in this study is its dUVA to dUVB irradiance ratio, which
      amounts to 24, instead of close to 10, for the simulated zenithal UV radiation
      (UV-SSR). PURPOSE/METHODS: The aim of our study was to compare photobiological
      effects induced, in human skin, by acute and semi-chronic exposure to simulated
      UV-DL with those induced by UV-SSR. RESULTS: Differences between UV doses needed
      to induce given biological effects after exposure to simulated UV-DL compared
      with UV-SSR indicate that the spectral distribution of the UV spectrum is of
      primary importance with regard to biological endpoints in the epidermis (SBC,
      p53, thymine dimers, Langerhans cells, and melanocyte alterations, etc.) and in
      the dermis (collagen, tenascin, etc.). Significant biological damage was noticed
      after 19 cumulative exposures to 0.5 minimum erythemal dose (MED) of UV-DL over 4
      weeks. 0.5 MED of UV-DL corresponds to 1/9 of the daily typical dose received in
      Paris in April, emphasizing the need for an efficient daily UV protection.
      CONCLUSION: Simulated UV daylight is a relevant new tool for daily
      photoprotection studies.

PMID- 16606412
TI  - Biological effect of far-infrared therapy on increasing skin microcirculation in
      rats.
AB  - BACKGROUND/PURPOSE: Insufficient microcirculation of skin leads to acute and
      chronic tissue ischemia in cases of trauma, reconstructive surgery, diabetes
      mellitus and peripheral arterial occlusive disease. The autonomic nervous system
      and nitric oxide (NO) play important roles in maintaining blood perfusion of the
      skin. Far-infrared (FIR) therapy provides low energy of light emitted from an
      artificial radiator and has been used to treat many vascular-related disorders.
      Nevertheless, the mechanisms through which FIR works remain unclear. The present
      study aims to test the hypothesis that the effect of FIR is through increasing
      skin microcirculation by a mechanism other than its thermal effect. METHODS:
      Sixty rats were used in the present study. A WS TY301 FIR emitter was placed 20
      cm above the rats. Skin temperature and blood flow were continuously measured by
      a K-type thermocouple. Under laboratory control, the abdominal skin temperature
      steadily increased from 38-39 degrees C, and was kept at constant temperature.
      Skin microcirculation was measured with a continuous laser Doppler flowmeter.
      RESULTS: There was no significant change of skin blood flow during FIR treatment.
      Skin blood flow increased significantly soon after the removal of the FIR
      emitter. The stimulating effect on skin blood flow was more significant in the
      rats treated with FIR for 45 min and could be sustained as long as 60 min. These
      findings suggested a non-thermic biological effect of FIR on skin
      microcirculation. The promotive effect of FIR on increasing skin blood flow was
      not influenced by pretreatment of APP (atropine, propranolol and phentolamine),
      but was suppressed by pretreatment with NG-nitro-L-arginine methyl ester (an
      endothelial nitric oxide synthase inhibitor). CONCLUSION: In conclusion, FIR
      therapy exerts a NO-related biological effect to increase skin microcirculation
      in rats. This might bring into perspective the clinical application of FIR to
      treat ischemic disease by augmenting L-arginine/NO pathway.

PMID- 16606413
TI  - Polymorphic light eruption may be associated with cigarette smoking and alcohol
      consumption.
AB  - BACKGROUND: Although the genetic influence on polymorphic light eruption (PLE) is
      well established, the role of lifestyle factors is less well defined. METHODS: A
      retrospective case-control study was conducted that included 74 PLE patients and
      102 controls. Each participant was interviewed about demographic, disease and
      lifestyle characteristics such as smoking, alcohol consumption and use of
      medications. Multivariate logistic regression models were used to calculate
      adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Compared
      with the controls, patients with PLE were significantly more likely to be younger
      females (P<0.05). Univariate analysis did not show a significant association
      between any of the smoking-related questions and PLE. However, after adjusting
      for gender and drinking alcohol, patients with PLE were significantly more likely
      to smoke 15 cigarettes or more daily [adjusted OR=4.06 (95% CI=1.19, 13.80)
      compared with 0 daily cigarettes] than controls. Participants who consumed six or
      more drinks a week were less likely to have PLE [adjusted OR=0.24 (95% CI=0.07,
      0.80)]. In contrast, women who used oral anticonceptives for a longer period were
      four-fold more likely to have PLE [adjusted OR=4.74 (95% CI=1.33, 16.86)].
      CONCLUSION: Several lifestyle factors may be associated with PLE, but further
      studies are warranted to confirm these retrospective findings.

PMID- 16606414
TI  - Compliance and data reliability in sun exposure studies with diaries and
      personal, electronic UV dosimeters.
AB  - BACKGROUND/PURPOSE: Skin cancer risk estimations are based on sun exposure data.
      However, the reliability of collected data in personal ultraviolet (UV)
      dosimeters studies has not previously been validated. We aimed at investigating
      the data reliability and subject compliance in a study of sun exposure behaviour
      among 407 subjects (age range, 4-68 years) during 54 943 days based on time
      stamped personal UV dosimeter readings and diary records. METHODS: By comparing
      diary records and UV dosimeter readings on a daily basis, we investigated subject
      compliance, total sun exposure record, reasons for non-responding along with
      rates of diary completing errors. Efforts to improve compliance were described.
      RESULTS: The subject compliance rate was median 93.5% (percent days where the
      diary was completed and the UV dosimeter was worn). The total sun exposure record
      rate was median 84.1% (percent of participation days with both UV dosimeter and
      diary records and where the UV dosimeter was worn). Children, adolescents and
      golfers had lower sun exposure record rates than the rest of the groups (P<0.05).
      No significant difference was found between males and females (P=0.15). The 17
      non-responders were 10 children, three adolescents, one sun worshipper, two
      golfers and one gardener. Correctable diary completing mistakes were found in
      3.1% of the days. Children made more completing mistakes than adults (P=0.001).
      The average estimated error rate was 3.3% and was higher for children (6.3%) and
      adolescents (3.6%) than the adult groups (2.4%). CONCLUSION: High subject
      compliance rate and data reliability were obtained because the investigators were
      service minded but persistent, offering dosimeter maintenance service within 24 h
      and scrutinized data for errors and mistakes.

PMID- 16606415
TI  - Experimental evaluation of cyadox phototoxicity to Balb/c mouse skin.
AB  - BACKGROUND: Cyadox is a veterinary drug mainly used as an effective antimicrobial
      promoter in animal husbandry. It was reported that the other quinoxaline-1,4
      dioxide compounds had phototoxicity, but only few data are reported on
      phototoxicity of cyadox. This study was performed to evaluate the phototoxicity
      of cyadox on skin. METHODS: Eighty mice were equally divided into eight groups.
      Five groups with ultraviolet A (UVA) irradiation for 2 h (21 J/cm2) were
      administered at doses of 0, 10, 50, 200 mg/kg cyadox and 50 mg/kg olaquindox,
      respectively, and others as controls without irradiation administered at doses of
      0, 200 mg/kg cyadox and 50 mg/kg olaquindox, respectively. Drugs were
      administered by gavage once daily with a suspension in 0.8% carboxymethyl
      cellulose for consecutive 4 days. After administration, a recovery period of 7
      days was arranged. Histopathological examination of auricular skin was performed
      on days 5 and 12. Measurement of auricular thickness, gross pathology and
      erythema score were conducted once daily. RESULTS: Cyadox groups (200, 50 and 10
      mg/kg) with irradiation had erythema and oedema of auricular skin with dose
      response relationship, which gradually convalesced after dosing and irradiation
      ceased. Severe erythema, oedema and necrosis of auricles were observed on
      olaquindox group with irradiation. CONCLUSION: The phototoxicity of cyadox was
      mild and reversible, which demonstrated a good safety profile of cyadox in terms
      of phototoxicity.

PMID- 16606416
TI  - Characteristics of 5-aminolaevulinic acid-induced protoporphyrin IX fluorescence
      in human skin in vivo.
AB  - BACKGROUND/PURPOSE: Topical photodynamic therapy (PDT) is increasingly being used
      to treat skin cancers. Knowledge of the detailed characteristics of 5
      aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence in
      diseased and normal skin is incomplete. Understanding the characteristics of PpIX
      fluorescence in normal skin may facilitate optimization of PDT regimes while
      minimizing side effects in the surrounding normal skin. We investigated the
      characteristics of ALA-induced PpIX fluorescence in normal skin. METHODS: ALA was
      applied to the arm, back and leg skin of 21 healthy volunteers for 1-6 h, and
      PpIX fluorescence was measured for up to 24 h after ALA application using a
      fluorescent spectrometer. The effect of tape stripping on fluorescence was also
      examined. RESULTS: Considerable inter-subject variation was observed in the time
      to reach peak PpIX fluorescence. Intra-subject variation in the time to peak
      fluorescence was dependent on ALA application time. Six hours after ALA
      application, no significant difference was observed in the degree of fluorescence
      achieved irrespective of ALA application times ranging between 1 and 6 h. PpIX
      fluorescence was reduced on the leg and increased by tape stripping. CONCLUSIONS:
      Marked inter- and intra-subject variation in ALA-induced PpIX fluorescence occurs
      in normal human skin. ALA application time, body site and the state of the
      stratum corneum are all determinants of PpIX fluorescence within subjects and
      these factors need to be taken into account in optimization of PDT regimes.

PMID- 16606417
TI  - Photolocalized purpura during ciprofloxacin therapy.
AB  - Photosensitivity reactions reported with ciprofloxacin mimic those of sunburn,
      with erythema and edema in the milder forms, and painful blistering with
      subsequent peeling when severe. Purpuric eruptions during treatment with
      ciprofloxacin have been rarely reported. We describe a 30-year-old man who was
      given a 15-day course with ciprofloxacin 500 mg twice a day for a prostatitis.
      Coinciding with sun exposure, he developed a purpuric, pruriginous eruption on
      his lower extremities, consisting of erythematous, petechial lesions located on
      the anterior aspect of his thighs and legs, clearly delimited by his bathing
      suit. The lesions cleared completely after the discontinuation of the drug and
      treatment with topical clobetasol. The acute reaction observed in our patient
      differed from a classical sunburn, consisting of confluent petechias, strictly
      limited to sunlight-exposed areas, and accompanied by pruritus. Photoexposed
      purpuric eruptions should be considered as another side effect of ciprofloxacin
      therapy in addition to phosensitivity rashes.

PMID- 16606418
TI  - Population health improvement and rural hospital balanced scorecards.

PMID- 16606419
TI  - Emergency Medical Services and the federal government's evolving role: what rural
      and frontier Emergency Medical Services advocates should know.

PMID- 16606420
TI  - Expected annual emergency miles per ambulance: an indicator for measuring
      availability of Emergency Medical Services resources.
AB  - CONTEXT: To ensure equitable access to prehospital care, as recommended by the
      Rural and Frontier Emergency Medical Services (EMS) Agenda for the Future,
      policymakers will need a uniform measure of EMS infrastructure. PURPOSE AND
      METHODS: This paper proposes a county-level indicator of EMS resource
      availability that takes into consideration existing EMS resources (ambulances),
      population health and demographics, and geographic factors. The indicator, the
      EXpected annual emergency miles per AMBulance (EXAMB), provides a basis for
      comparing ambulance availability across counties within states. A method for
      calculating the EXAMB indicator is demonstrated using data from 5 states.
      FINDINGS: The EXAMB indicator was negatively correlated with ambulance
      availability per 100,000 population in 4 of the 5 states in the study. The
      indicator was positively correlated with rurality in 3 states. In Mississippi,
      South Carolina, and Wyoming, whole-county health professional shortage areas had
      median EXAMB values 45%-81% higher than those of the non-health professional
      shortage areas counties. CONCLUSIONS: Future research should explore the
      relationship of the EXAMB to EMS outcomes, with the ultimate goal of developing a
      nationally recognized indicator of "adequate" EMS resource availability.

PMID- 16606421
TI  - Prevalence and trends in smoking: a national rural study.
AB  - CONTEXT: Cigarette smoking is the leading preventable cause of death in the
      United States. PURPOSE: To estimate the prevalence of and recent trends in
      smoking among adults by type of rural location and by state. METHODS: Random
      digit telephone survey of adults aged 18 years or older who participated in the
      Behavioral Risk Factor Surveillance System in 1994-1996 (n = 342,055) and 2000
      2001 (n = 385,384). The main outcome measure was current cigarette smoking,
      defined as persons who smoke every day or some days, while nonsmokers were those
      who smoke not at all or reported never having smoked as many as 100 cigarettes.
      FINDINGS: The prevalence of smoking changed little from the mid-1990s; in 2000
      2001, it was 22.0% in urban areas, 24.9% in rural adjacent areas, 24.0% in large
      rural nonadjacent areas, and 24.9% in small rural nonadjacent areas. For rural
      locations combined, smoking prevalence was not below the 12% goal of Healthy
      People 2010 for any state, although the 12.5% prevalence in rural Utah approached
      this target. Prevalence was > or = 28% for rural residents of Kentucky, Ohio, and
      Indiana. Since the mid-1990s, the prevalence of smoking for rural respondents
      decreased by more than 2 percentage points in 6 states: California, Connecticut,
      Maryland, North Carolina, Tennessee, and Utah. However, it increased by 2
      percentage points or more in 10 states: Alabama, Delaware, Georgia,
      Massachusetts, Michigan, Mississippi, New Hampshire, Oklahoma, South Carolina,
      and Texas. CONCLUSIONS: Smoking remains a refractory public health problem.
      Better ways to curb smoking in rural America are needed.

PMID- 16606422
TI  - Antitobacco media awareness of rural youth compared to suburban and urban youth
      in Indiana.
AB  - PURPOSE: This study examined the awareness and impact of antitobacco media
      messages among rural, suburban, and urban youth. METHOD: Self-administered
      questionnaires were received from 1,622, 1,059, and 1,177 middle school (sixth,
      seventh, and eighth grade) students in rural, suburban, and urban locations,
      respectively. Logistic regression compared media awareness and impact among the
      groups, controlling for grade, gender, race, and smoking behavior. RESULTS:
      Compared to rural youth, suburban youth were more likely to recall media messages
      about the dangerous health effects of tobacco use (odds ratio [OR] = 1.94) and
      have their personal choice to use tobacco affected by the messages (OR = 1.85).
      Suburban and urban youth more often recalled antitobacco messages (OR = 2.00 and
      2.15), reported that the messages made them think about the dangers of tobacco
      use (OR = 2.02 and 1.47), believed that these ads prevent youth from initiating
      tobacco use (OR = 3.21 and 1.46) and stop youth from using tobacco (OR = 2.25 and
      1.47), and recalled seeing specific campaign television ads (OR = 3.72 and 3.57).
      Urban youth were more likely to recall specific campaign messages on the radio
      (OR = 1.58). Neither suburban nor urban youth differed from the rural youth on
      whether the campaign-specific radio and television ads made them think about not
      using tobacco. CONCLUSIONS: The results support the need for targeting
      antitobacco media announcements to youth, based on their residence.

PMID- 16606423
TI  - Rural-urban differences in colon cancer risk in blacks and whites: the North
      Carolina Colon Cancer Study.
AB  - CONTEXT: Geographic and racial variations in cancer incidence have been observed.
      Studies of colorectal carcinoma indicate a higher incidence and mortality rate
      for blacks than for whites in the United States. PURPOSE: We evaluated the effect
      of rural versus urban residence on colon cancer risk and stage of disease at
      diagnosis in blacks and whites. METHODS: Interviews were conducted with 558 colon
      cancer cases and 952 controls enrolled in the North Carolina Colon Cancer Study,
      a population-based case-control study of blacks and whites residing in 33
      contiguous counties. FINDINGS: Residence in a rural area was associated with
      increased colon cancer risk (odds ratio, 1.4; 95% confidence interval, 1.1-1.8).
      This association was no longer significant after controlling for recent use of
      colorectal cancer screening tests (odds ratio, 1.2; 95% confidence interval, 0.9
      1.6). Risk estimates were not modified by race nor were they markedly different
      for extent of disease at diagnosis. However, colorectal cancer screening rates
      were lower for blacks than for whites. CONCLUSION: Our findings suggest that
      rural blacks and whites are at increased risk of colon cancer regardless of stage
      of disease at diagnosis than their urban counterparts; this relationship may be
      mediated by screening behavior.

PMID- 16606424
TI  - Psychosocial differences between whites and African Americans living with
      HIV/AIDS in rural areas of 13 US states.
AB  - CONTEXT: Acquired immunodeficiency syndrome (AIDS) prevalence rates are
      increasing rapidly in rural areas of the United States. As rural African
      Americans are increasingly affected by human immunodeficiency virus (HIV), it is
      important to identify psychosocial factors unique to this group so that AIDS
      mental health interventions can be culturally contextualized to meet their unique
      needs. PURPOSE: The current study characterized psychosocial functioning in 43
      rural African Americans living with HIV/AIDS and compared their levels of
      functioning to those of 196 HIV-infected rural white persons. METHODS: All
      participants were recruited through AIDS service organizations in 13 US states.
      Surveys were completed as part of a preintervention phase of a randomized
      clinical trial evaluating 2 mental health interventions for HIV-infected rural
      persons. FINDINGS: Compared to their white counterparts, fewer African Americans
      had progressed to AIDS. African American participants also reported higher levels
      of coping self-efficacy, more support from family members, and marginally fewer
      depressive symptoms, and they engaged in more active coping. African Americans
      who had greater HIV disease severity also received less support from family
      members and experienced more loneliness. CONCLUSIONS: Study findings caution that
      rural African Americans and whites living with HIV disease should not be
      considered a homogeneous group.

PMID- 16606425
TI  - Geographic access to health care for rural Medicare beneficiaries.
AB  - CONTEXT: Patients in rural areas may use less medical care than those living in
      urban areas. This could be due to differences in travel distance and time and a
      utilization of a different mix of generalists and specialists for their care.
      PURPOSE: To compare the travel times, distances, and physician specialty mix of
      all Medicare patients living in Alaska, Idaho, North Carolina, South Carolina,
      and Washington. METHODS: Retrospective design, using 1998 Medicare billing data.
      Travel time was determined by computing the road distance between 2 population
      centroids: the patient's and the provider's zone improvement plan codes.
      FINDINGS: There were 2,220,841 patients and 39,780 providers in the cohort,
      including 6,405 (16.1%) generalists, 24,772 (62.3%) specialists, and 8,603
      (21.6%) nonphysician providers. There were 20,693,828 patient visits during the
      study. The median overall 1-way travel distance and time was 7.7 miles
      (interquartile range 1.9-18.7 miles) and 11.7 minutes (interquartile range 3.0
      25.7 minutes). The patients in rural areas needed to travel 2 to 3 times farther
      to see medical and surgical specialists than those living in urban areas. Rural
      residents with heart disease, cancer, depression, or needing complex cardiac
      procedures or cancer treatment traveled the farthest. Increasing rurality was
      also related to decreased visits to specialists and an increasing reliance on
      generalists. CONCLUSIONS: Residents of rural areas have increased travel distance
      and time compared to their urban counterparts. This is particularly true for
      rural residents with specific diagnoses or those undergoing specific procedures.
      Our results suggest that most rural residents do not rely on urban areas for much
      of their care.

PMID- 16606426
TI  - Variations in health insurance coverage for rural and urban nonelderly adult
      residents of Florida, Indiana, and Kansas.
AB  - CONTEXT: Evidence exists for differences in health insurance coverage among
      states, but less is known about variations across different kinds of communities
      within states. PURPOSE: This article assesses the role of residential setting
      (metropolitan county, rural adjacent, and rural nonadjacent) in health insurance
      coverage for adult residents, under age 65, using data from large-scale surveys
      collected in 3 diverse states (Florida, Indiana, and Kansas). METHODS:
      Descriptive statistics are provided, and logistic regression models are used to
      examine the relationship between uninsurance status and residential settings
      while controlling for personal characteristics. Adjusted uninsurance rates by
      residential settings are presented for each state. FINDINGS: Residential settings
      are significantly associated with uninsurance status in 2 of the 3 states we
      examined. We find that adult Floridians of rural adjacent counties are more
      likely to be uninsured than those in urban counties, but, for Indiana residents,
      uninsurance status is comparable between urban and rural adjacent residents.
      Rural nonadjacent Indiana residents are more likely to be uninsured compared to
      those in urban counties. The insurance status of adult Kansans does not vary
      across residential settings. CONCLUSION: Residential settings are significantly
      associated with being uninsured, but the significance of this link between
      residential locations and uninsurance status varies from state to state.

PMID- 16606427
TI  - Characteristics of registered nurses in rural versus urban areas: implications
      for strategies to alleviate nursing shortages in the United States.
AB  - METHODS: This study compares characteristics of rural and urban registered nurses
      (RNs) in the United States using data from the 2000 National Sample Survey of
      Registered Nurses. RNs in 3 types of rural areas are examined using the rural
      urban commuting area taxonomy. FINDINGS: Rural and urban RNs are similar in age
      and sex; nonwhites and Hispanics are underrepresented in both groups. Rural RNs
      have less nursing education, are less likely to work in hospitals, and are more
      likely to work full time and in public/community health than urban RNs. The more
      rural an RN's residence, the more likely he/she commutes to another area for work
      and the lower salary he/she receives. CONCLUSIONS: Strategies to reduce nurse
      shortages should consider differences in education, work patterns, and commuting
      behavior among rural and urban RNs. Solutions for rural areas require
      understanding of the impact of the workplace on these behaviors.

PMID- 16606428
TI  - Technology, job satisfaction, and retention: rural mental health practitioners.
AB  - CONTEXT: Job satisfaction as it relates to retention of mental health
      professionals is a major problem in rural areas. Several authors have suggested
      that technology can positively influence job satisfaction and thus improve
      retention. OBJECTIVES: This study examined technology use and technology
      expertise in relationship to job satisfaction. It is based on a theoretical
      framework that asserts as technology use increases, communication among providers
      and access to educational and consultative resources increase as well, resulting
      in a boost in professional support and a reduction in isolation. METHODS: Surveys
      were sent to 320 providers in rural southeast Ohio; 163 returned usable surveys.
      FINDINGS: There was a statistically significant relationship between the
      combination of technology use and expertise and job satisfaction. Use alone,
      however, was not significant. Despite the fact that over 90% of respondents had
      access to both a computer and the Internet, just 45% used technology to
      communicate with peers and nearly 96% indicated that they never or rarely used
      the Internet for educational programs. CONCLUSIONS: The results challenge the
      assertion that technology plays a major role in job satisfaction and rural
      retention since access and perceived expertise did not guarantee technology
      usage. Decisions to stay or leave a rural practice involve a complex array of
      factors. Technology, with its ability to link providers to resources outside the
      geographic bounds of an individual's practice, may play a role, but since its
      adoption can be costly in both time and money, future studies need to determine
      its place in the retention model.

PMID- 16606429
TI  - Physical activity among rural older adults with diabetes.
AB  - PURPOSE: This analysis describes physical activity levels and factors associated
      with physical activity in an ethnically diverse (African American, Native
      American, white) sample of rural older adults with diabetes. METHOD: Data were
      collected using a population-based, cross-sectional stratified random sample
      survey of 701 community-dwelling elders with diabetes completed in 2 rural North
      Carolina counties. Outcome measures were as follows: first, physical activity in
      the past year, and second, days physically active in the prior week (0-7).
      Potential correlates included personal and health characteristics and were
      evaluated for statistical significance using logistic regression models.
      FINDINGS: About half (52.5%) of the participants stated that they had engaged in
      physical activity in the past year. Among those, 42.5% stated that they had no
      days with at least 30 minutes of continuous physical activity in the prior week,
      while 21.5% reported daily physical activity. Common activities were walking and
      housework. Correlates of physical activity in the past year and days active in
      the prior week included measures of physical health and mobility. CONCLUSIONS:
      Physical activity in this ethnically diverse sample of rural elders with diabetes
      is limited. Effort must be invested to increase physical activity in these
      groups.

PMID- 16606430
TI  - Perspectives on health among adult users of illicit stimulant drugs in rural
      Ohio.
AB  - CONTEXT: Although the nonmedical use of stimulant drugs such as cocaine and
      methamphetamine is increasingly common in many rural areas of the United States,
      little is known about the health beliefs of people who use these drugs. PURPOSE:
      This research describes illicit stimulant drug users' views on health and health
      related concepts that may affect their utilization of health care services.
      METHODS: A respondent-driven sampling plan was used to recruit 249 not-in
      treatment, nonmedical stimulant drug users who were residing in 3 rural counties
      in west central Ohio. A structured questionnaire administered by trained
      interviewers was used to collect information on a range of topics, including
      current drug use, self-reported health status, perceived need for substance abuse
      treatment, and beliefs about health and health services. FINDINGS: Participants
      reported using a wide variety of drugs nonmedically, some by injection. Alcohol
      and marijuana were the most commonly used drugs in the 30 days prior to the
      interview. Powder cocaine was used by 72.3% of the sample, crack by 68.3%, and
      methamphetamine by 29.7%. Fair or poor health status was reported by 41.3% of the
      participants. Only 20.9% of the sample felt they needed drug abuse treatment.
      Less than one third of the sample reported that they would feel comfortable
      talking to a physician about their drug use, and 65.1% said they preferred taking
      care of their problems without getting professional help. CONCLUSIONS: Stimulant
      drug users in rural Ohio are involved with a range of substances and hold health
      beliefs that may impede health services utilization.

PMID- 16606431
TI  - Planning and providing end-of-life care in rural areas.
AB  - CONTEXT: Approximately 20% of North Americans and 25% of Europeans reside in
      rural areas. Planning and providing end-of-life (EOL) care in rural areas
      presents some unique challenges. PURPOSE: In order to understand these
      challenges, and other important issues or circumstances, a literature search was
      conducted to assess the state of science on rural EOL care. METHODS: The
      following databases were searched for articles published from 1988 through 2003:
      EMBASE, Medline, CINAHL, AHMED, Psychinfo, ERIC, HealthStar, Sociological
      Abstracts, and Cochrane. All articles were systematically reviewed. FINDINGS:
      Thirty-six research articles were identified. Only 1 randomized controlled trial
      was located. Most research was single site, small sample, and
      exploratory/descriptive in design. Four distinct foci in this body of research
      were noted: (1) identifying and describing differences between urban and rural
      EOL care; (2) exploring rural EOL care; (3) assessing the EOL needs and wishes of
      terminally ill or dying persons, their family members, and health care
      professionals in rural areas; and (4) exploring EOL education for rural EOL care
      providers. CONCLUSIONS: Although rural EOL care research is not extensive, the
      existing literature is helpful for realizing the importance of EOL care in rural
      communities, as well as for conceptualizing and planning EOL care in rural
      communities. One of the chief considerations for rural EOL care is that dying at
      home is a common wish, with home-based nursing care a key factor for this to
      become a reality. Another chief consideration is ensuring all rural health care
      professionals are both prepared for and supported while delivering EOL care.

PMID- 16606432
TI  - Family perspectives on pathways to mental health care for children and youth in
      rural communities.
AB  - CONTEXT: There is insufficient literature documenting the mental health
      experiences and needs of rural communities, and a lack of focus on children in
      particular. This is of concern given that up to 20% of children and youth suffer
      from a diagnosable mental health problem. PURPOSE: This study examines issues of
      access to mental health care for children and youth in rural communities from the
      family perspective. METHODS: In-depth interviews were conducted in rural Ontario,
      Canada, with 30 parents of children aged 3-17 who had been diagnosed with
      emotional and behavioral disorders. FINDINGS: Interview data indicate 3 overall
      thematic areas that describe the main barriers and facilitators to care. These
      include personal, systemic, and environmental factors. Family members are
      constantly negotiating ongoing tension, struggle, and contradiction vis-a-vis
      their attempts to access and provide mental health care. Most factors identified
      as barriers are also, under different circumstances, facilitators. Analysis
      clustered around the contrasts, contradictions, and paradoxes present throughout
      the interviews. CONCLUSIONS: The route to mental health care for children in
      rural communities is complex, dynamic, and nonlinear, with multiple roadblocks.
      Although faced with multiple roadblocks, there are also several factors that help
      minimize these barriers.

PMID- 16606433
TI  - The characteristics of successful family physicians in rural Nebraska: a
      qualitative study of physician interviews.
AB  - CONTEXT: In studying physician shortage issues, few studies have utilized
      individual interviews, allowing rural physicians to voice their own stories.
      PURPOSE: To explore rural physicians' unique characteristics affecting their
      decisions and satisfactions with practice in a rural area. METHODS: A qualitative
      interview study with 11 Nebraska family physicians practicing in rural (frontier)
      areas. FINDINGS: Previous experience and preference for a rural lifestyle, desire
      for autonomy, a wide scope of practice, and close relationships with patients
      defined those physicians choosing rural practice.

PMID- 16606434
TI  - Epidemiology studies in critical care.
AB  - Epidemiology studies are an essential part of clinical research, often forming
      the foundation for studies ranked more highly in the hierarchy of evidence-based
      medicine. Studies of sepsis to date have been conducted on local, regional,
      national and international scales, with the majority conducted in the past 5
      years. Longitudinal epidemiology studies convey an important additional aspect of
      the healthcare burden from disease, and may additionally serve to compare the
      effectiveness and efficiency of healthcare systems, to examine specific patient
      care strategies and to perform quality control analyses.

PMID- 16606435
TI  - Percutaneous dilatational tracheostomy versus surgical tracheostomy in critically
      ill patients: a systematic review and meta-analysis.
AB  - INTRODUCTION: Tracheostomy is one of the more commonly performed procedures in
      critically ill patients yet the optimal method of performing tracheostomies in
      this population remains to be established. The aim of this study was to
      systematically review and quantitatively synthesize all randomized clinical
      trials (RCTs), comparing elective percutaneous dilatational tracheostomy (PDT)
      and surgical tracheostomy (ST) in adult critically ill patients with regards to
      major short and long term outcomes. METHODS: MEDLINE, EMBASE, CINAHL and the
      Cochrane Controlled Clinical Trials Register databases were searched to identify
      relevant studies. Additionally, bibliographies and selected conference
      proceedings were reviewed, and experts in the field and manufacturers of two PDT
      kits were contacted. Randomized clinical trials comparing any method of elective
      PDT to ST that included critically ill adults and reported at least one
      clinically relevant outcome were included. Data extracted included trial
      characteristics, measures of study validity, and clinically relevant outcomes.
      RESULTS: Seventeen RCTs involving 1,212 patients were included. Most PDTs used a
      multiple dilator technique and were performed in the intensive care unit (ICU).
      The pooled odds ratio (OR) for wound infection was 0.28 (95% confidence interval
      (CI), 0.16 to 0.49, p < 0.0005), indicating a significant reduction with PDT
      compared to ST. Overall, PDT was equivalent to ST for bleeding, major peri
      procedural and long-term complications; however, subgroup analysis suggested PDT
      resulted in a lower incidence of bleeding (OR = 0.29 (95% CI 0.12 to 0.75, p =
      0.01)) and death (OR = 0.71 (95% CI 0.50 to 1.0, p = 0.05)) when the STs were
      performed in the operating theatre. CONCLUSION: PDT reduces the overall incidence
      of wound infection and may further reduce clinical relevant bleeding and
      mortality when compared with ST performed in the operating theatre. PDT,
      performed in the ICU, should be considered the procedure of choice for performing
      elective tracheostomies in critically ill adult patients.

PMID- 16606436
TI  - Oxygenation effect of interventional lung assist in a lavage model of acute lung
      injury: a prospective experimental study.
AB  - INTRODUCTION: The aim of the study was to test the hypothesis that a pumpless
      arteriovenous extracorporeal membrane oxygenator (interventional lung assist
      (ILA)) does not significantly improve oxygenation in a lavage model of acute lung
      injury. METHODS: The study was designed as a prospective experimental study. The
      experiments were performed on seven pigs (48-60 kg body weight). The pigs were
      anesthetized and mechanically ventilated. Both femoral arteries and one femoral
      vein were cannulated and connected with ILA. Acute lung injury was induced by
      repeated bronchoalveolar lavage until the arterial partial pressure of O2 was
      lower than 100 Torr for at least 30 minutes during ventilation with 100% O2.
      RESULTS: ILA was applied with different blood flow rates through either one or
      both femoral arteries. Measurements were repeated at different degrees of
      pulmonary gas exchange impairment with the pulmonary venous admixture ranging
      from 35.0% to 70.6%. The mean (+/- standard deviation) blood flow through ILA was
      15.5 (+/- 3.9)% and 21.7 (+/- 4.9)% of cardiac output with one and both arteries
      open, respectively. ILA significantly increased the arterial partial pressure of
      O2 from 64 (+/- 13) Torr to 71 (+/- 14) Torr and 74 (+/- 17) Torr with blood flow
      through one and both femoral arteries, respectively. O2 delivery through ILA
      increased with extracorporeal shunt flow (36 (+/- 14) ml O2/min versus 47 (+/-
      17) ml O2/min) and reduced arterialization of the inlet blood. Pulmonary artery
      pressures were significantly reduced when ILA was in operation. CONCLUSION:
      Oxygenation is increased by ILA in severe lung injury. This effect is significant
      but small. The results indicate that the ILA use may not be justified if the
      improvement of oxygenation is the primary therapy goal.

PMID- 16606437
TI  - The use of moderate hypothermia during cardiac surgery is associated with
      repression of tumour necrosis factor-alpha via inhibition of activating protein
      1: an experimental study.
AB  - INTRODUCTION: The use of moderate hypothermia during experimental cardiac surgery
      is associated with decreased expression of tumour necrosis factor (TNF)-alpha in
      myocardium and with myocardial protection. In order to identify the cellular
      mechanisms that lead to that repression, we investigated the effect of
      hypothermia during cardiac surgery on both main signalling pathways involved in
      systemic inflammation, namely the nuclear factor-kappaB (NF-kappaB) and
      activating protein-1 pathways. METHOD: Twelve female pigs were randomly subjected
      to standardized cardiopulmonary bypass with moderate hypothermia or normothermia
      (temperature 28 degrees C and 37 degrees C, respectively; six pigs in each
      group). Myocardial probes were sampled from the right ventricle before, during
      and 6 hours after bypass. We detected mRNA encoding TNF-alpha by competitive RT
      PCR and measured protein levels of TNF-alpha, inducible nitric oxide synthase and
      cyclo-oxygenase-2 by Western blotting. Finally, we assessed the activation of NF
      kappaB and activating protein-1, as well as phosphorylation of p38 mitogen
      activated protein kinase by electrophoretic mobility shift assay with super shift
      and/or Western blot. RESULTS: During and after cardiac surgery, animals subjected
      to hypothermia exhibited lower expression of TNF-alpha and cyclo-oxygenase-2 but
      not of inducible nitric oxide synthase. This was associated with lower activation
      of p38 mitogen-activated protein kinase and of its downstream effector activating
      protein-1 in hypothermic animals. In contrast, NF-kappaB activity was no
      different between groups. CONCLUSION: These findings indicate that the repression
      of TNF-alpha associated with moderate hypothermia during cardiac surgery is
      associated with inhibition of the mitogen-activated protein kinase p38/activating
      protein-1 pathway and not with inhibition of NF-kappaB. The use of moderate
      hypothermia during cardiac surgery may mitigate the perioperative systemic
      inflammatory response and its complications.

PMID- 16606438
TI  - HER4 in breast cancer: comparison of antibodies against intra- and extra-cellular
      domains of HER4.
AB  - INTRODUCTION: We have previously linked HER4 expression with increased survival
      in breast cancer. However, other reports have associated HER4 with adverse
      prognostic significance. One possible explanation for the conflicting reports may
      be that these results are antibody dependent. The HER4 protein is enzymatically
      cleaved, which may alter the function of its intracellular domain (ICD). We have
      therefore compared the staining patterns of antibodies against its intracellular
      and extracellular domains using tissue microarray technology. METHODS:
      Immunohistochemistry was performed and evaluated on tumours from 402 tamoxifen
      treated oestrogen receptor positive patients. The HFR1 antibody recognises the
      ICD of HER4 and thus recognises both the intact receptor and the cleaved ICD. The
      H4.77.16 clone recognises an extracellular domain of HER4 and thus detects the
      full length receptor only. RESULTS: Both antibodies demonstrated nuclear,
      cytoplasmic and membranous staining. Concordance between the membrane staining
      patterns was high (88.44%, kappa 0.426). The HFR1 antibody, however, demonstrated
      generally higher levels of cytoplasmic staining (concordance 74.77%, kappa
      0.351). The antibodies demonstrated very different patterns of nuclear staining.
      Over 60% of patients stained with the H4.77.16 had no nuclear staining whereas
      the vast majority showed staining with the HFR1 antibody (concordance 40.12%,
      kappa 0.051). Neither antibody demonstrated relationships between membranous or
      cytoplasmic HER4 staining and survival, although associations were seen with
      known poor prognostic markers. Cases with H4.77.16-determined nuclear staining
      had significantly poorer survival outcomes. CONCLUSION: The difference in antigen
      site may explain the different staining patterns we have seen with respect to
      location; with each antibody appearing to select for distinct compartments. Thus,
      HFR1 may select for cytoplasmic and nuclear HER4 ICD, whilst H4.77.16 selects for
      membranous HER4 and/or HER4 being recycled in cytoplasm or nucleus. This ability
      to distinguish between site and function of HER4 and its fragments is
      particularly important, with recent evidence highlighting the different functions
      of nuclear and mitochondrial HER4.

PMID- 16606440
TI  - Severe heat stroke with multiple organ dysfunction.

PMID- 16606439
TI  - Genes regulated by estrogen in breast tumor cells in vitro are similarly
      regulated in vivo in tumor xenografts and human breast tumors.
AB  - BACKGROUND: Estrogen plays a central role in breast cancer pathogenesis. Although
      many studies have characterized the estrogen regulation of genes using in vitro
      cell culture models by global mRNA expression profiling, it is not clear whether
      these genes are similarly regulated in vivo or how they might be coordinately
      expressed in primary human tumors. RESULTS: We generated DNA microarray-based
      gene expression profiles from three estrogen receptor alpha (ERalpha)-positive
      breast cancer cell lines stimulated by 17beta-estradiol (E2) in vitro over a time
      course, as well as from MCF-7 cells grown as xenografts in ovariectomized athymic
      nude mice with E2 supplementation and after its withdrawal. When the patterns of
      genes regulated by E2 in vitro were compared to those obtained from xenografts,
      we found a remarkable overlap (over 40%) of genes regulated by E2 in both
      contexts. These patterns were compared to those obtained from published clinical
      data sets. We show that, as a group, E2-regulated genes from our preclinical
      models were co-expressed with ERalpha in a panel of ERalpha+ breast tumor mRNA
      profiles, when corrections were made for patient age, as well as with
      progesterone receptor. Furthermore, the E2-regulated genes were significantly
      enriched for transcriptional targets of the myc oncogene and were found to be
      coordinately expressed with Myc in human tumors. CONCLUSION: Our results provide
      significant validation of a widely used in vitro model of estrogen signaling as
      being pathologically relevant to breast cancers in vivo.

PMID- 16606441
TI  - Voluntary activation failure is detectable in some myositis patients with
      persisting quadriceps femoris weakness: an observational study.
AB  - This cross-sectional, observational study was undertaken to examine whether
      voluntary activation failure could contribute to the persisting weakness observed
      in some patients with treated idiopathic inflammatory myositis. In 20 patients
      with myositis of more than six months' duration (5 males, 15 females; mean [+/- 1
      SD] age 53 11 years) and 102 normal subjects (44 males, 58 females; mean age 32 8
      years), isometric maximum voluntary contractions (MVCs) of the dominant
      quadriceps femoris (QF) were quantified. Absolute MVC results of normal subjects
      and patients were then normalised with respect to lean body mass (force per units
      of lean body mass), giving a result in Newtons per kilogram. Based on mass
      normalised force data of normal subjects, patients were arbitrarily stratified
      into "weak" and "not weak" subgroups. During further MVC attempts, the "twitch
      interpolation" technique was used to assess whether the QF voluntary activation
      of patients was complete. This technique relies on the fact that, because muscle
      activation is incomplete during submaximal voluntary contractions, electrical
      stimulation of the muscle can induce force increments superimposed on the
      submaximal voluntary force being generated. No between-gender differences were
      seen in the mass-normalised MVC results of healthy subjects, so the gender
      combined results of 6.6 (1.5) N/kg were used for patient stratification. No
      between-gender difference was found for mass-normalised MVCs in patients: males
      5.4 (3.2) and females 3.0 (1.7) N/kg (p > 0.05). Mass-normalised MVCs of male
      patients were as great as those of normal subjects (p > 0.05), but mass
      normalised MVCs of female patients were significantly smaller than those of the
      normal subjects (p < 0.001). Only one of the six "not weak" patients exhibited
      interpolated twitches during electrical stimulation, but six of the 14 "weak"
      patients did, the biggest twitches being seen in the weakest patient. That
      interpolated twitches can be induced in some myositis patients with ongoing QF
      weakness during supposed MVCs clearly suggests that voluntary activation failure
      does contribute to QF weakness in those patients.

PMID- 16606442
TI  - The in vivo expression of actin/salt-resistant hyperactive DNase I inhibits the
      development of anti-ssDNA and anti-histone autoantibodies in a murine model of
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is characterised by the production of
      autoantibodies against ubiquitous antigens, especially nuclear components.
      Evidence makes it clear that the development of these autoantibodies is an
      antigen-driven process and that immune complexes involving DNA-containing
      antigens play a key role in the disease process. In rodents, DNase I is the major
      endonuclease present in saliva, urine and plasma, where it catalyses the
      hydrolysis of DNA, and impaired DNase function has been implicated in the
      pathogenesis of SLE. In this study we have evaluated the effects of transgenic
      over-expression of murine DNase I endonucleases in vivo in a mouse model of
      lupus. We generated transgenic mice having T-cells that express either wild-type
      DNase I (wt.DNase I) or a mutant DNase I (ash.DNase I), engineered for three new
      properties - resistance to inhibition by G-actin, resistance to inhibition by
      physiological saline and hyperactivity compared to wild type. By crossing these
      transgenic mice with a murine strain that develops SLE we found that, compared to
      control non-transgenic littermates or wt.DNase I transgenic mice, the ash.DNase I
      mutant provided significant protection from the development of anti-single
      stranded DNA and anti-histone antibodies, but not of renal disease. In summary,
      this is the first study in vivo to directly test the effects of long-term
      increased expression of DNase I on the development of SLE. Our results are in
      line with previous reports on the possible clinical benefits of recombinant DNase
      I treatment in SLE, and extend them further to the use of engineered DNase I
      variants with increased activity and resistance to physiological inhibitors.

PMID- 16606443
TI  - Comparative analysis of Saccharomyces cerevisiae WW domains and their interacting
      proteins.
AB  - BACKGROUND: The WW domain is found in a large number of eukaryotic proteins
      implicated in a variety of cellular processes. WW domains bind proline-rich
      protein and peptide ligands, but the protein interaction partners of many WW
      domain-containing proteins in Saccharomyces cerevisiae are largely unknown.
      RESULTS: We used protein microarray technology to generate a protein interaction
      map for 12 of the 13 WW domains present in proteins of the yeast S. cerevisiae.
      We observed 587 interactions between these 12 domains and 207 proteins, most of
      which have not previously been described. We analyzed the representation of
      functional annotations within the network, identifying enrichments for proteins
      with peroxisomal localization, as well as for proteins involved in protein
      turnover and cofactor biosynthesis. We compared orthologs of the interacting
      proteins to identify conserved motifs known to mediate WW domain interactions,
      and found substantial evidence for the structural conservation of such binding
      motifs throughout the yeast lineages. The comparative approach also revealed that
      several of the WW domain-containing proteins themselves have evolutionarily
      conserved WW domain binding sites, suggesting a functional role for inter- or
      intramolecular association between proteins that harbor WW domains. On the basis
      of these results, we propose a model for the tuning of interactions between WW
      domains and their protein interaction partners. CONCLUSION: Protein microarrays
      provide an appealing alternative to existing techniques for the construction of
      protein interaction networks. Here we built a network composed of WW domain
      protein interactions that illuminates novel features of WW domain-containing
      proteins and their protein interaction partners.

PMID- 16606444
TI  - Shift working and risk of lipid disorders: a cross-sectional study.
AB  - BACKGROUND: previous studies have indicated on association between shift work and
      lipid profile disturbances. Lipid profile disturbances could be due to internal
      desynchronization. The aim of this study was to analyze whether there is
      relationship between shift work and serum lipids, fasting blood glucose and
      hypertension. RESULTS: A total of 424 rail road workers between the ages of 21
      and 64 years in this study filled out a questionnaire, and total cholesterol,
      triglyceride and HDL-C concentration were measured after 12-hours fasting.
      Association between shift work and biochemical variables and blood pressure were
      measured. The X2 and fisher's exact test was used for comparing the qualitative
      variables and for quantitative variables with normal distribution we used the
      parametric tests. Odds ratio (OR) with the 95% confidence interval (95% CI) was
      used for comparing the proportions of risk variables.Sub-populations in this
      study were consisting of 158 (37.3%) shift workers and 266 (62.7%) day workers.
      High levels of total cholesterol (> 200 mg/dl) and LDL-cholesterol (> 130 mg/dl)
      were significantly more prevalent in nearly all groups of shift workers
      irrespective of age. But there is no differences in the serum levels of
      triglyceride, HDL-C, fasting blood glucose and blood pressure between shift
      workers and day workers.Adjusted Odd's ratio for the effect of shift working on
      high serum total cholesterol and LDL-C level were 2.11(95%CI: 1.33-3.36) and
      1.76(95%CI: 1.09-2.83), respectively. CONCLUSION: This study showed that high
      serum total cholesterol and LDL-C level were more common in shift workers than in
      day workers. This finding persisted after adjustment was made for age and food
      type. But there was no difference in the prevalence of HDL-C, triglyceride,
      fasting blood glucose and hypertension between shift working and day working. It
      was concluded that shift work is a risk factor for lipid profile disturbances.

PMID- 16606445
TI  - Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative
      and neoplastic liver.
AB  - BACKGROUND: Epigenetic changes during ageing and their relationship with cancer
      are under the focus of intense research. RASSF1A and NORE1A are novel genes
      acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A
      has not been previously investigated in the human liver, recent reports have
      suggested that RASSF1A is frequently epigenetically methylated not only in HCC
      but also in the cirrhotic liver. METHODS: To address whether epigenetic changes
      take place in connection to age and/or to the underlying disease, we investigated
      RASSF1A and NORE1A gene promoter methylation by conventional methylation specific
      PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring
      regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia), dysplastic
      (large regenerative, low and high grade dysplastic nodules) and neoplastic
      (hepatocellular adenoma and carcinoma) growths. RESULTS: In the hepatitic liver
      (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC) we found widespread
      RASSF1A gene promoter methylation with a methylation index that increased from
      regenerative conditions (cirrhosis) to hepatocellular nodules (p < 0.01) to HCC
      (p < 0.001). In the non-hepatitic liver a consistent pattern of gene methylation
      was also found in both lesional (focal nodular hyperplasia and hepatocellular
      adenoma) and non-lesional tissue. Specifically, hepatocellular adenomas (HA)
      showed a methylation index significantly higher than that detected in focal
      nodular hyperplasia (FNH) (p < 0.01) and in non-lesional tissue (p < 0.001). In
      non-lesional liver also the methylation index gradually increased by ageing (p =
      0.002), suggesting a progressive spreading of methylated cells over time. As
      opposed to RASSF1A gene promoter methylation, NORE1A gene was never found
      epigenetically alterated in both hepatitic and non-hepatitic liver. CONCLUSION:
      We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A
      gene is increasingly methylated, that this condition takes place as an age
      related phenomenon and that the early setting and spreading over time of an
      epigenetically methylated hepatocyte subpopulation, might be related to liver
      tumorigenesis.

PMID- 16606446
TI  - Recursive SVM feature selection and sample classification for mass-spectrometry
      and microarray data.
AB  - BACKGROUND: Like microarray-based investigations, high-throughput proteomics
      techniques require machine learning algorithms to identify biomarkers that are
      informative for biological classification problems. Feature selection and
      classification algorithms need to be robust to noise and outliers in the data.
      RESULTS: We developed a recursive support vector machine (R-SVM) algorithm to
      select important genes/biomarkers for the classification of noisy data. We
      compared its performance to a similar, state-of-the-art method (SVM recursive
      feature elimination or SVM-RFE), paying special attention to the ability of
      recovering the true informative genes/biomarkers and the robustness to outliers
      in the data. Simulation experiments show that a 5%- approximately 20% improvement
      over SVM-RFE can be achieved regard to these properties. The SVM-based methods
      are also compared with a conventional univariate method and their respective
      strengths and weaknesses are discussed. R-SVM was applied to two sets of SELDI
      TOF-MS proteomics data, one from a human breast cancer study and the other from a
      study on rat liver cirrhosis. Important biomarkers found by the algorithm were
      validated by follow-up biological experiments. CONCLUSION: The proposed R-SVM
      method is suitable for analyzing noisy high-throughput proteomics and microarray
      data and it outperforms SVM-RFE in the robustness to noise and in the ability to
      recover informative features. The multivariate SVM-based method outperforms the
      univariate method in the classification performance, but univariate methods can
      reveal more of the differentially expressed features especially when there are
      correlations between the features.

PMID- 16606447
TI  - Detection of Norovirus genogroup I and II by multiplex real-time RT- PCR using a
      3'-minor groove binder-DNA probe.
AB  - BACKGROUND: Due to an increasing number of norovirus infections in the last years
      rapid, specific, and sensitive diagnostic tools are needed. Reverse transcriptase
      polymerase chain reactions (RT-PCR) have become the methods of choice. To
      minimize the working time and the risk of carryover contamination during the
      multi-step procedure of PCR the multiplex real-time RT-PCR for the simultaneous
      detection of genogroup I (GI) and II (GII) offers advantages for the handling of
      large amounts of clinical specimens. METHODS: We have developed and evaluated a
      multiplex one-tube RT-PCR using a combination of optimized GI and GII specific
      primers located in the junction between ORF1 and ORF2 of the norovirus genome.
      For the detection of GI samples, a 3'-minor groove binder-DNA probe (GI-MGB
      probe) were designed and used for the multiplex real-time PCR. RESULTS:
      Comparable results to those of our in-house nested PCR and monoplex real-time-PCR
      were only obtained using the GI specific MGB-probe. The MGB-probe forms extremely
      stable duplexes with single-stranded DNA targets, which enabled us to design a
      shorter probe (length 15 nucleotides) hybridizing to a more conserved part of the
      GI sequences. 97% of 100 previously norovirus positive specimens (tested by
      nested PCR and/or monoplex real-time PCR) were detected by the multiplex real
      time PCR. A broad dynamic range from 2 x 10(1) to 2 x 10(7) genomic equivalents
      per assay using plasmid DNA standards for GI and GII were obtained and viral
      loads between 2.5 x 10(2) and 2 x 10(12) copies per ml stool suspension were
      detected. CONCLUSION: The one-tube multiplex RT real-time PCR using a minor
      groove binder-DNA probe for GI is a fast, specific, sensitive and cost-effective
      tool for the detection of norovirus infections in both mass outbreaks and
      sporadic cases and may have also applications in food and environmental testing.

PMID- 16606448
TI  - Disability weights for comorbidity and their influence on health-adjusted life
      expectancy.
AB  - BACKGROUND: Comorbidity complicates estimations of health-adjusted life
      expectancy (HALE) using disease prevalences and disability weights from Burden of
      Disease studies. Usually, the exact amount of comorbidity is unknown and no
      disability weights are defined for comorbidity. METHODS: Using data of the Dutch
      national burden of disease study, the effects of different methods to adjust for
      comorbidity on HALE calculations are estimated. The default multiplicative
      adjustment method to define disability weights for comorbidity is compared to
      HALE estimates without adjustment for comorbidity and to HALE estimates in which
      the amount of disability in patients with multiple diseases is solely determined
      by the disease that leads to most disability (the maximum adjustment method). To
      estimate the amount of comorbidity, independence between diseases is assumed.
      RESULTS: Compared to the multiplicative adjustment method, the maximum adjustment
      method lowers HALE estimates by 1.2 years for males and 1.9 years for females.
      Compared to no adjustment, a multiplicative adjustment lowers HALE estimates by
      1.0 years for males and 1.4 years for females. CONCLUSION: The differences in
      HALE caused by the different adjustment methods demonstrate that adjusting for
      comorbidity in HALE calculations is an important topic that needs more attention.
      More empirical research is needed to develop a more general theory as to how
      comorbidity influences disability.

PMID- 16606449
TI  - Correlation analysis of two-dimensional gel electrophoretic protein patterns and
      biological variables.
AB  - BACKGROUND: Two-dimensional gel electrophoresis (2DE) is a powerful technique to
      examine post-translational modifications of complexly modulated proteins.
      Currently, spot detection is a necessary step to assess relations between spots
      and biological variables. This often proves time consuming and difficult when
      working with non-perfect gels. We developed an analysis technique to measure
      correlation between 2DE images and biological variables on a pixel by pixel
      basis. After image alignment and normalization, the biological parameters and
      pixel values are replaced by their specific rank. These rank adjusted images and
      parameters are then put into a standard linear Pearson correlation and further
      tested for significance and variance. RESULTS: We validated this technique on a
      set of simulated 2DE images, which revealed also correct working under the
      presence of normalization factors. This was followed by an analysis of p53 2DE
      immunoblots from cancer cells, known to have unique signaling networks. Since p53
      is altered through these signaling networks, we expected to find correlations
      between the cancer type (acute lymphoblastic leukemia and acute myeloid leukemia)
      and the p53 profiles. A second correlation analysis revealed a more complex
      relation between the differentiation stage in acute myeloid leukemia and p53
      protein isoforms. CONCLUSION: The presented analysis method measures relations
      between 2DE images and external variables without requiring spot detection,
      thereby enabling the exploration of biosignatures of complex signaling networks
      in biological systems.

PMID- 16606450
TI  - Expression of Toll-like receptor 2 is up-regulated in monocytes from patients
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by
      pulmonary and systemic inflammation which flare-up during episodes of acute
      exacerbation (AECOPD). Given the role of Toll-like receptors (TLRs) in the
      induction of inflammatory responses we investigated the involvement of TLRs in
      COPD pathogenesis. METHODS: The expression of TLR-2, TLR-4 and CD14 in monocytes
      was analyzed by flow cytometry. To study the functional responses of these
      receptors, monocytes were stimulated with peptidoglycan or lipopolysaccharide and
      the amounts of TNFalpha and IL-6 secreted were determined by ELISA. RESULTS: We
      found that the expression of TLR-2 was up-regulated in peripheral blood monocytes
      from COPD patients, either clinically stable or during AECOPD, as compared to
      never smokers or smokers with normal lung function. Upon stimulation with TLR-2
      ligand monocytes from COPD patients secreted increased amounts of cytokines than
      similarly stimulated monocytes from never smokers and smokers. In contrast, the
      expressions of TLR-4 and CD14 were not significantly different between groups,
      and the response to lipopolysaccharide (a TLR-4 ligand) stimulation was not
      significantly different either. At discharge from hospital TLR-2 expression was
      down-regulated in peripheral blood monocytes from AECOPD patients. This could be
      due to the treatment with systemic steroids because, in vitro, steroids down
      regulated TLR-2 expression in a dose-dependent manner. Finally, we demonstrated
      that IL-6, whose plasma levels are elevated in patients, up-regulated in vitro
      TLR-2 expression in monocytes from never smokers. CONCLUSION: Our results reveal
      abnormalities in TLRs expression in COPD patients and highlight its potential
      relationship with systemic inflammation in these patients.

PMID- 16606451
TI  - Contributions of androgen and estrogen to fetal programming of ovarian
      dysfunction.
AB  - In female mammals, including humans, deviations from normal androgenic or
      estrogenic exposure during fetal development are detrimental to subsequent adult
      ovarian function. Androgen deficiency, without accompanying estrogen deficit, has
      little apparent impact on ovarian development. Fetal estrogen deficiency, on the
      other hand, results in impaired oocyte and follicle development, immature and
      abnormal adult ovaries, and excessive ovarian stimulation from endogenous
      gonadotropins ultimately generating hemorrhagic follicles. Complete estrogen
      deficiency lasting into adulthood results in partial ovarian masculinization.
      Fetal androgen excess, on the other hand, mediated either by direct androgen
      action or following androgen aromatization to estrogen, reprograms ovarian
      development and reproductive neuroendocrinology to mimic that found in women with
      polycystic ovary syndrome: enlarged, polyfollicular, hyperandrogenic, anovulatory
      ovaries with accompanying LH hypersecretion. Oocyte developmental competence is
      also compromised. Insulin is implicated in the mechanism of both anovulation and
      deficient oocyte development. Fetal estrogen excess induces somewhat similar
      disruption of adult ovarian function to fetal androgen excess. Understanding the
      quality of the fetal female sex steroid hormone environment is thus becoming
      increasingly important in improving our knowledge of mechanisms underlying a
      variety of female reproductive pathologies.

PMID- 16606453
TI  - Accuracy and completeness of mortality data in the Department of Veterans
      Affairs.
AB  - BACKGROUND: One of the national mortality databases in the U.S. is the
      Beneficiary Identification and Record Locator Subsystem (BIRLS) Death File that
      contains death dates of those who have received any benefits from the Department
      of Veterans Affairs (VA). The completeness of this database was shown to vary
      widely from cohort to cohort in previous studies. Three other sources of death
      dates are available in the VA that can complement the BIRLS Death File. The
      objective of this study is to evaluate the completeness and accuracy of death
      dates in the four sources available in the VA and to examine whether these four
      sources can be combined into a database with improved completeness and accuracy.
      METHODS: A random sample of 3,000 was drawn from 8.3 million veterans who
      received benefits from the VA between 1997 and 1999 and were alive on January 1,
      1999 according to at least one source. Death dates found in BIRLS Death File,
      Medical SAS Inpatient Datasets, Medicare Vital Status, and Social Security
      Administration (SSA) Death Master File were compared with dates obtained from the
      National Death Index. A combined dataset from these sources was also compared
      with National Death Index dates. RESULTS: Compared with the National Death Index,
      sensitivity (or the percentage of death dates correctly recorded in a source) was
      77.4% for BIRLS Death File, 12.0% for Medical SAS Inpatient Datasets, 83.2% for
      Medicare Vital Status, and 92.1% for SSA Death Master File. Over 95% of death
      dates in these sources agreed exactly with dates from the National Death Index.
      Death dates in the combined dataset demonstrated 98.3% sensitivity and 97.6%
      exact agreement with dates from the National Death Index. CONCLUSION: The BIRLS
      Death File is not an adequate source of mortality data for the VA population due
      to incompleteness. When the four sources of mortality data are carefully
      combined, the resulting dataset can provide more timely data for death
      ascertainment than the National Death Index and has comparable accuracy and
      completeness.

PMID- 16606452
TI  - Effect of repaglinide on endothelial dysfunction during a glucose tolerance test
      in subjects with impaired glucose tolerance.
AB  - BACKGROUND: Impaired glucose tolerance (IGT) is associated with increased
      cardiovascular risk. The pathophysiological mechanisms linking post-challenge
      hyperglycemia to accelerated atherosclerosis, however remain to be elucidated.
      METHODS: A prospective, open, randomised, cross-over study was performed to
      investigate the effect of 2 mg repaglinide on hyperglycemia and endothelial
      function during an oral glucose tolerance test (75 g glucose) in 12 subjects with
      diagnosed IGT. Blood samples for determination of plasma glucose were drawn
      fasting, 1 and 2 hours after glucose ingestion. Endothelial function was assessed
      by measuring flow-mediated dilatation (FMD) of the brachial artery with high
      resolution ultrasound. RESULTS: Administration of repaglinide resulted in a
      significant reduction of plasma glucose at 2 hours (172.8+/-48.4 vs. 138.3+/-41.2
      mg/dl; p < 0.001). The flow-mediated dilatation (FMD) 2 hours after the glucose
      load was significantly reduced in comparison to fasting in the control group
      (6.21+/-2.69 vs. 7.98+/-2.24 %; p = 0.028), whereas after theadministration of
      repaglinide the FMD was not significantly different to fasting values (7.24+/
      2.57 vs. 8.18+/-2.93 %; p = n.s.). Linear and logistic regression analysis
      revealed that only the change of glucose was significantly correlated to the
      change of FMD observed (p < 0.001). Regression analysis after grouping for
      treatment and time confirmed the strong negative association of the changes of
      plasma glucose and FMD and indicate that the effect of repaglinide observed is
      based on the reduction glycemia. CONCLUSION: In subjects with IGT, the
      endothelial dysfunction observed after a glucose challenge is related to the
      extent of hyperglycemia. Reduction of hyperglycemia by repaglinide reduces
      endothelial dysfunction in a glucose dependent manner.

PMID- 16606454
TI  - Post-traumatic stress disorder following patient assaults among staff members of
      mental health hospitals: a prospective longitudinal study.
AB  - BACKGROUND: Violence by patients against staff members in mental health
      institutions has become an important challenge. Violent attacks may not only
      cause bodily injuries but can also have posttraumatic consequences with high
      rates of stress for mental health staff. This study prospectively assessed
      posttraumatic stress disorder (PTSD) in employees who were severely assaulted by
      patients in nine German state mental health institutions. METHODS: During the
      study period of six months 46 assaulted staff members were reported. Each staff
      member was interviewed three times after the violent incident, using the Impact
      of Event Scale-Revised (IES-R), a widely used PTSD research tool, as well as the
      Posttraumatic Stress Disorder Checklist--Civilian (PCL-C). RESULTS: In the
      baseline assessment following an assault by a patient, eight subjects (17%) met
      the criteria for PTSD. After two and six months, three and four subjects
      respectively still met diagnosis criteria. CONCLUSION: A small minority of
      assaulted employees suffer from PTSD for several months after a patient assault.

PMID- 16606455
TI  - Diagnostic accuracy of the Eurotest for dementia: a naturalistic, multicenter
      phase II study.
AB  - BACKGROUND: Available screening tests for dementia are of limited usefulness
      because they are influenced by the patient's culture and educational level. The
      Eurotest, an instrument based on the knowledge and handling of money, was
      designed to overcome these limitations. The objective of this study was to
      evaluate the diagnostic accuracy of the Eurotest in identifying dementia in
      customary clinical practice. METHODS: A cross-sectional, multi-center,
      naturalistic phase II study was conducted. The Eurotest was administered to
      consecutive patients, older than 60 years, in general neurology clinics. The
      patients' condition was classified as dementia or no dementia according to DSM-IV
      diagnostic criteria. We calculated sensitivity (Sn), specificity (Sp) and area
      under the ROC curves (aROC) with 95% confidence intervals. The influence of
      social and educational factors on scores was evaluated with multiple linear
      regression analysis, and the influence of these factors on diagnostic accuracy
      was evaluated with logistic regression. RESULTS: Sixteen neurologists recruited a
      total of 516 participants: 101 with dementia, 380 without dementia, and 35 who
      were excluded. Of the 481 participants who took the Eurotest, 38.7% were totally
      or functionally illiterate and 45.5% had received no formal education. Mean time
      needed to administer the test was 8.2+/-2.0 minutes. The best cut-off point was
      20/21, with Sn = 0.91 (0.84-0.96), Sp = 0.82 (0.77-0.85), and aROC = 0.93 (0.91
      0.95). Neither the scores on the Eurotest nor its diagnostic accuracy were
      influenced by social or educational factors. CONCLUSION: This naturalistic and
      pragmatic study shows that the Eurotest is a rapid, simple and useful screening
      instrument, which is free from educational influences, and has appropriate
      internal and external validity.

PMID- 16606456
TI  - Co-utilization of L-arabinose and D-xylose by laboratory and industrial
      Saccharomyces cerevisiae strains.
AB  - BACKGROUND: Fermentation of lignocellulosic biomass is an attractive alternative
      for the production of bioethanol. Traditionally, the yeast Saccharomyces
      cerevisiae is used in industrial ethanol fermentations. However, S. cerevisiae is
      naturally not able to ferment the pentose sugars D-xylose and L-arabinose, which
      are present in high amounts in lignocellulosic raw materials. RESULTS: We
      describe the engineering of laboratory and industrial S. cerevisiae strains to co
      ferment the pentose sugars D-xylose and L-arabinose. Introduction of a fungal
      xylose and a bacterial arabinose pathway resulted in strains able to grow on both
      pentose sugars. Introduction of a xylose pathway into an arabinose-fermenting
      laboratory strain resulted in nearly complete conversion of arabinose into
      arabitol due to the L-arabinose reductase activity of the xylose reductase. The
      industrial strain displayed lower arabitol yield and increased ethanol yield from
      xylose and arabinose. CONCLUSION: Our work demonstrates simultaneous co
      utilization of xylose and arabinose in recombinant strains of S. cerevisiae. In
      addition, the co-utilization of arabinose together with xylose significantly
      reduced formation of the by-product xylitol, which contributed to improved
      ethanol production.

PMID- 16606457
TI  - Utility of BRAF V600E mutation detection in cytologically indeterminate thyroid
      nodules.
AB  - BACKGROUND: Fine needle aspiration (FNA) is widely utilized for evaluation of
      patients with thyroid nodules. However, approximately 30% are indeterminate for
      malignancy. Recently, a mutation in the BRAF gene has been reported to be the
      most common genetic event in papillary thyroid carcinoma (PTC). In this
      retrospective study, we assessed the utility of BRAF V600E mutation detection for
      refining indeterminate preoperative cytologic diagnoses in patients with PTC.
      METHODS: Archival indeterminate thyroid FNAs and corresponding formalin-fixed,
      paraffin-embedded (FFPE) surgical samples with PTC were identified in our patient
      files. DNA extracted from slide scape lysates and 5 mum FFPE sections were
      evaluated for the BRAF V600E mutation using LightCycler PCR and fluorescent
      melting curve analysis (LCPCR). Amplification products that showed deviation from
      the wild-type genomic DNA melting peak, discordant FNA and FFPE matched pairs,
      and all benign control samples, underwent direct DNA sequencing. RESULTS: A total
      of 19 indeterminate thyroid FNAs demonstrating PTC on FFPE surgical samples were
      included in the study. Using BRAF mutation analysis, the preoperative diagnosis
      of PTC was confirmed in 3/19 (15.8%) FNA samples that could not be conclusively
      diagnosed on cytology alone. However, 9/19 (47.4%) FFPE tissue samples were
      positive for the V600E mutation. Of the discordant pairs, 5/6 FNAs contained less
      than 50% tumor cells. CONCLUSION: When used with indeterminate FNA samples, BRAF
      mutation analysis may be a useful adjunct technique for confirming the diagnosis
      of malignancy in an otherwise equivocal case. However, overall tumor cell content
      of some archival FNA smear slides is a limiting factor for mutation detection.

PMID- 16606458
TI  - Percutaneous septal ablation for left mid-ventricular obstructive hypertrophic
      cardiomyopathy: a case report.
AB  - BACKGROUND: Mid-ventricular obstructive hypertrophic cardiomyopathy (MVOHC) is a
      rare type of cardiomyopathy. The diagnosis is based on the hourglass appearance
      on the left ventriculogram and the presence of pressure gradient between apical
      and basal chamber of the ventriculum on the hemodynamic assessment. CASE
      PRESENTATION: The present case represents successful percutaneous treatment with
      septal ablation to patient with MVOHC associated with systolic anterior motion of
      the mitral valve and obstruction at both the mid-ventricular and outflow levels.
      CONCLUSION: Alcohol septal ablation has been proposed as less invasive
      alternatives to surgery in patients with MVOHC.

PMID- 16606459
TI  - Leptin and adiponectin in relation to body fat percentage, waist to hip ratio and
      the apoB/apoA1 ratio in Asian Indian and Caucasian men and women.
AB  - BACKGROUND: Asian Indian immigrants have an increased risk for developing
      cardiovascular disease (CVD); however, there is very little data examining how
      the adipokines leptin and adiponectin relate to CVD risk factors such as body fat
      percentage (BF%), waist to hip ratio (WHR) and the apoB/apoA1 ratio in Asian
      Indian men and women living in Canada. SUBJECTS AND METHODS: A cross-sectional
      study comparing leptin, adiponectin, lipoproteins and anthropometric parameters
      in Asian Indian men and women to Caucasian men and women (4 groups).
      Anthropometric data (BMI, BF%, WHR), circulating lipids (apoA1, apoB, total
      cholesterol, and HDL-cholesterol), leptin and adiponectin were measured. RESULTS:
      Asian Indian men and women had higher leptin and lower adiponectin concentrations
      then Caucasian men and women, respectively. Leptin (positively) and adiponectin
      (negatively) correlated with anthropometric parameters and lipoproteins in all
      four groups. Using stepwise forward multiple regression, a model including TC/HDL
      C ratio, WHR, BF%, hip circumference and waist circumference predicted 74.2% of
      leptin concentration in men. In women, apoB, BF%, waist circumference and age
      predicted 77.5% of leptin concentration. Adiponectin concentrations in men were
      predicted (30.2%) by HDL-C, total cholesterol, hip circumference and BF% while in
      women 41.2% of adiponectin concentration was predicted by the apoB/apoA1 ratio,
      WHR and age. CONCLUSION: As is evident from our data, there is a strong
      relationship between leptin, adiponectin, and abdominal obesity with increased
      CVD risk, as assessed by the apoB/apoA1 ratio. Dysregulation of these parameters
      may account for the increased risk of CVD in Asian Indians.

PMID- 16606460
TI  - QPath: a method for querying pathways in a protein-protein interaction network.
AB  - BACKGROUND: Sequence comparison is one of the most prominent tools in biological
      research, and is instrumental in studying gene function and evolution. The rapid
      development of high-throughput technologies for measuring protein interactions
      calls for extending this fundamental operation to the level of pathways in
      protein networks. RESULTS: We present a comprehensive framework for protein
      network searches using pathway queries. Given a linear query pathway and a
      network of interest, our algorithm, QPath, efficiently searches the network for
      homologous pathways, allowing both insertions and deletions of proteins in the
      identified pathways. Matched pathways are automatically scored according to their
      variation from the query pathway in terms of the protein insertions and deletions
      they employ, the sequence similarity of their constituent proteins to the query
      proteins, and the reliability of their constituent interactions. We applied QPath
      to systematically infer protein pathways in fly using an extensive collection of
      271 putative pathways from yeast. QPath identified 69 conserved pathways whose
      members were both functionally enriched and coherently expressed. The resulting
      pathways tended to preserve the function of the original query pathways, allowing
      us to derive a first annotated map of conserved protein pathways in fly.
      CONCLUSION: Pathway homology searches using QPath provide a powerful approach for
      identifying biologically significant pathways and inferring their function. The
      growing amounts of protein interactions in public databases underscore the
      importance of our network querying framework for mining protein network data.

PMID- 16606461
TI  - Perioperative intraperitoneal chemotherapy for peritoneal surface malignancy.
AB  - The treatment of peritoneal surface malignancy mainly focuses on diffuse
      malignant peritoneal mesothelioma, pseudomyxoma peritonei from appendiceal
      cancer, and peritoneal dissemination from gastrointestinal and ovarian cancers.
      Cancer progression causes peritoneal implants to be distributed throughout the
      abdominopelvic cavity. These nodules plus the ascitic fluid result in abdominal
      distension. As the disease progresses, these tumors cause intestinal obstruction
      leading to debilitating symptoms and a greatly impaired quality of life. In the
      past, the prognosis of patients with peritoneal surface malignancy was regarded
      dismal and cure was not an option. Recently, cytoreductive surgery combined with
      perioperative intraperitoneal chemotherapy has shown an improved survival in
      selected patients with this disease. To date, multiple different treatment
      regimens of perioperative intraperitoneal chemotherapy have been used. This
      review focuses on the perioperative intraperitoneal chemotherapy currently in use
      in conjunction with cytoreductive surgery for the treatment of peritoneal surface
      malignancy at the Washington Cancer Institute.

PMID- 16606463
TI  - Impact of methylphenidate formulation on treatment patterns and hospitalizations:
      a retrospective analysis.
AB  - BACKGROUND: While stimulant therapy has been shown to be effective in the
      treatment of attention-deficit/hyperactivity disorder (ADHD), there is less
      information concerning differences between alternative stimulant medications. The
      purpose of this study is to examine how different formulations of methylphenidate
      (MPH) affect treatment patterns and hospitalizations. METHODS: From a large
      claims database we retrospectively identified individuals age 6 or older who were
      diagnosed with ADHD and who received either once daily, extended-release oral
      system methylphenidate (OROS MPH) (e.g., Concerta) or three-times daily immediate
      release generic methylphenidate (TID MPH). There were 5,939 individuals included
      in the analysis--4,785 who initiated therapy with OROS MPH and 1,154 who
      initiated therapy with TID MPH. We used Analyses of Covariance (ANCOVAs) to
      examine differences in treatment patterns between individuals who initiated
      therapy on OROS MPH and those who initiated therapy on TID MPH. We used logistic
      and negative binomial multivariate regressions to examine the probability of
      being hospitalized and the hospital length of stay. RESULTS: Controlling for
      demographic characteristics, patient general health status, and comorbid
      diagnoses, significantly fewer individuals who initiated therapy with OROS MPH
      had a 15-day gap in therapy (85% vs. 97%, p < 0.0001 or a 30-day gap in therapy
      (77% vs. 95%, p < 0.0001) or switched to another ADHD medication (27% vs. 68%, p
      < 0.0001). Individuals who initiated therapy with OROS MPH stayed on therapy
      significantly longer (199 vs. 108 mean days, p < 0.0001) and more individuals
      received medication for 90% (24% vs. 5%, p < 0.0001), 80% (29% vs. 7%, p <
      0.0001), or 75% (30% vs. 7%, p < 0.0001) of the days during the first year post
      initiation of therapy. Individuals who initiated therapy on OROS MPH were also
      significantly less likely to be hospitalized (odds ratio = 0.67, p = 0.0454) and
      stayed, on average, 0.69 fewer days in the hospital (p = 0.0035). CONCLUSION:
      Results demonstrate that among individuals diagnosed with ADHD who receive either
      OROS MPH or TID MPH, the use of OROS MPH is associated with fewer gaps in
      medication, less switches in medication, and more days on intent-to-treat
      therapy. In addition, use of OROS MPH compared to TID MPH was associated with
      improved outcomes, as measured by the reduced use of hospitalizations.

PMID- 16606462
TI  - Prevalence of metabolic syndrome-related disorders in a large adult population in
      Turkey.
AB  - BACKGROUND: There are few existing large population studies on the epidemiology
      of metabolic syndrome-related disorders of Turkey. The purpose of this study was
      to assess the prevalence of metabolic syndrome-related disorders in the Turkish
      adult population, to address sex, age, educational and geographical differences,
      and to examine blood pressure, body mass index, fasting blood glucose and serum
      lipids in Turkey. METHODS: This study was executed under the population study
      "The Healthy Nutrition for Healthy Heart Study" conducted between December 2000
      and December 2002 by the Health Ministry of Turkey. Overall, 15,468 Caucasian
      inhabitants aged over 30 were recruited in 14 centers in the seven main different
      regions of Turkey. The data were analyzed with the Students' t, ANOVA or Chi
      Square tests. RESULTS: Overall, more than one-third (35.08 %) of the participants
      was obese. The hypertensive people ratio in the population was 13.66 %, while
      these ratios for DM and metabolic syndrome were 4.16 % and 17.91 %, respectively.
      The prevalence of hypertension, metabolic syndrome and obesity were higher in
      females than males, whereas diabetes mellitus was higher in males than females.
      The prevalence of metabolic syndrome and related disorders were found to be
      significantly different across educational attainments for both men and women.
      The prevalence of hypertension increased with age, while it was remarkable that
      in the age group of 60-69 years, prevalence of diabetes mellitus and metabolic
      syndrome reached a peak value and than decreased. For obesity, the peak
      prevalence occurred in the 50-59 year old group. The prevalence of metabolic
      syndrome and related disorders were found to be significantly different according
      to geographical region. CONCLUSION: In conclusion, high prevalence of obesity and
      metabolic syndrome, particularly among women, is one of the major public health
      problems in Turkey. Interestingly, obesity prevalence is relatively high, but the
      prevalence of hypertension and hypercholesterolemia is relatively low in Turkish
      people. Future studies may focus on elucidating the reasons behind this
      controversy. Our findings may be helpful in formulating public health policy and
      prevention strategies on future health in Turkey.

PMID- 16606464
TI  - Mycobacterium haemophilum osteomyelitis: case report and review of the
      literature.
AB  - BACKGROUND: Mycobacterium haemophilum is a slow-growing, fastidious, iron
      requiring microorganism that, relative to other non-tuberculous mycobacterial
      species, has rarely been documented as a cause of human infection. This
      microorganism appears to be acquired via environmental exposure although its
      natural habitat and mode of acquisition are unknown. It has primarily been
      implicated as a cause of ulcerating cutaneous or subcutaneous nodular skin
      lesions, particularly in immunocompromised patients, although infections at
      extracutaneous sites have also been described. Osteomyelitis, while rarely
      documented, appears to be an important complication of infection with M.
      haemophilum in these patients. CASE PRESENTATION: We describe a unique case of
      culture-confirmed M. haemophilum osteomyelitis in an adult woman with
      polycythemia vera and review the world literature on bone infections due to this
      organism. CONCLUSION: Mycobacterium haemophilum is an important but infrequently
      encountered cause of osteomyelitis in immunocompromised patients, often requiring
      months to years of medical therapy, with or without surgery, to effect a clinical
      cure.

PMID- 16606465
TI  - Primary care patients reporting concerns about their gambling frequently have
      other co-occurring lifestyle and mental health issues.
AB  - BACKGROUND: Problem gambling often goes undetected by family physicians but may
      be associated with stress-related medical problems as well as mental disorders
      and substance abuse. Family physicians are often first in line to identify these
      problems and to provide a proper referral. The aim of this study was to compare a
      group of primary care patients who identified concerns with their gambling
      behavior with the total population of screened patients in relation to co
      morbidity of other lifestyle risk factors or mental health issues. METHODS: This
      is a cross sectional study comparing patients identified as worrying about their
      gambling behavior with the total screened patient population for co morbidity.
      The setting was 51 urban and rural New Zealand practices. Participants were
      consecutive adult patients per practice (N = 2,536) who completed a brief multi
      item tool screening primary care patients for lifestyle risk factors and mental
      health problems (smoking, alcohol and drug misuse, problem gambling, depression,
      anxiety, abuse, anger). Data analysis used descriptive statistics and non
      parametric binomial tests with adjusting for clustering by practitioner using
      STATA survey analysis. RESULTS: Approximately 3/100 (3%) answered yes to the
      gambling question. Those worried about gambling more likely to be male OR 1.85
      (95% CI 1.1 to 3.1). Increasing age reduced likelihood of gambling concerns -
      logistic regression for complex survey data OR = 0.99 (CI 95% 0.97 to 0.99) p =
      0.04 for each year older. Patients concerned about gambling were significantly
      more likely (all p < 0.0001) to have concerns about their smoking, use of
      recreational drugs, and alcohol. Similarly there were more likely to indicate
      problems with depression, anxiety and anger control. No significant relationship
      with gambling worries was found for abuse, physical inactivity or weight
      concerns. Patients expressing concerns about gambling were significantly more
      likely to want help with smoking, other drug use, depression and anxiety.
      CONCLUSION: Our questionnaire identifies patients who express a need for help
      with gambling and other lifestyle and mental health issues. Screening for
      gambling in primary care has the potential to identify individuals with multiple
      co-occurring disorders.

PMID- 16606466
TI  - A computer-based medical record system and personal digital assistants to assess
      and follow patients with respiratory tract infections visiting a rural Kenyan
      health centre.
AB  - BACKGROUND: Clinical research can be facilitated by the use of informatics tools.
      We used an existing electronic medical record (EMR) system and personal data
      assistants (PDAs) to assess the characteristics and outcomes of patients with
      acute respiratory illnesses (ARIs) visiting a Kenyan rural health center.
      METHODS: We modified the existing EMR to include details on patients with ARIs.
      The EMR database was then used to identify patients with ARIs who were
      prospectively followed up by a research assistant who rode a bicycle to patients'
      homes and entered data into a PDA. RESULTS: A total of 2986 clinic visits for
      2009 adult patients with respiratory infections were registered in the database
      between August 2002 and January 2005; 433 patients were selected for outcome
      assessments. These patients were followed up in the villages and assessed at 7
      and 30 days later. Complete follow-up data were obtained on 381 patients (88%)
      and merged with data from the enrollment visit's electronic medical records and
      subsequent health center visits to assess duration of illness and complications.
      Symptoms improved at 7 and 30 days, but a substantial minority of patients had
      persistent symptoms. Eleven percent of patients sought additional care for their
      respiratory infection. CONCLUSION: EMRs and PDA are useful tools for performing
      prospective clinical research in resource constrained developing countries.

PMID- 16606467
TI  - NAC and DTT promote TGF-beta1 monomer formation: demonstration of competitive
      binding.
AB  - TGF-Beta plays an important role in the genesis and progression of pulmonary
      fibrosis. We sought to determine the role of mononuclear phagocytes in the
      activation of TGF-beta and found that freshly isolated peripheral blood monocytes
      spontaneously released TGF-beta. Stimulating these monocytes with GM-CSF or LPS,
      but not MCSF, augmented the activation of TGF-beta. In human monocytes, the free
      thiol compounds DTT and NAC decreased the activity of TGF-beta, without affecting
      TGF-beta mRNA transcription. Both NAC and DTT lessened the biological activity of
      recombinant active TGF-beta in a cell-free system. We found that NAC and DTT
      reduced dimeric active TGF-beta from a 25 kDa protein to 12.5 kDa inactive
      monomer. This conversion was reversed using the oxidizing agent diamide. Diamide
      also restored biological activity to NAC or DTT-treated TGF-beta. Reduction of
      TGF-beta to monomers could competitively inhibit active dimeric TGF-beta and
      block intracellular signaling events. Our observations suggest that modulation of
      the oxidative state of TGF-beta may be a novel therapeutic approach for patients
      with pulmonary fibrosis.

PMID- 16606468
TI  - Epidemiology of recreational exposure to freshwater cyanobacteria--an
      international prospective cohort study.
AB  - BACKGROUND: Case studies and anecdotal reports have documented a range of acute
      illnesses associated with exposure to cyanobacteria and their toxins in
      recreational waters. The epidemiological data to date are limited; we sought to
      improve on the design of some previously conducted studies in order to facilitate
      revision and refinement of guidelines for exposure to cyanobacteria in
      recreational waters. METHODS: A prospective cohort study was conducted to
      investigate the incidence of acute symptoms in individuals exposed, through
      recreational activities, to low (cell surface area < 2.4 mm2/mL), medium (2.4
      12.0 mm2/mL) and high (> 12.0 mm2/mL) levels of cyanobacteria in lakes and rivers
      in southeast Queensland, the central coast area of New South Wales, and northeast
      and central Florida. Multivariable logistic regression analyses were employed;
      models adjusted for region, age, smoking, prior history of asthma, hay fever or
      skin disease (eczema or dermatitis) and clustering by household. RESULTS: Of
      individuals approached, 3,595 met the eligibility criteria, 3,193 (89%) agreed to
      participate and 1,331 (37%) completed both the questionnaire and follow-up
      interview. Respiratory symptoms were 2.1 (95%CI: 1.1-4.0) times more likely to be
      reported by subjects exposed to high levels of cyanobacteria than by those
      exposed to low levels. Similarly, when grouping all reported symptoms,
      individuals exposed to high levels of cyanobacteria were 1.7 (95%CI: 1.0-2.8)
      times more likely to report symptoms than their low-level cyanobacteria-exposed
      counterparts. CONCLUSION: A significant increase in reporting of minor self
      limiting symptoms, particularly respiratory symptoms, was associated with
      exposure to higher levels of cyanobacteria of mixed genera. We suggest that
      exposure to cyanobacteria based on total cell surface area above 12 mm2/mL could
      result in increased incidence of symptoms. The potential for severe, life
      threatening cyanobacteria-related illness is likely to be greater in recreational
      waters that have significant levels of cyanobacterial toxins, so future
      epidemiological investigations should be directed towards recreational exposure
      to cyanotoxins.

PMID- 16606469
TI  - ModuleFinder and CoReg: alternative tools for linking gene expression modules
      with promoter sequences motifs to uncover gene regulation mechanisms in plants.
AB  - BACKGROUND: Uncovering the key sequence elements in gene promoters that regulate
      the expression of plant genomes is a huge task that will require a series of
      complementary methods for prediction, substantial innovations in experimental
      validation and a much greater understanding of the role of combinatorial control
      in the regulation of plant gene expression. RESULTS: To add to this larger
      process and to provide alternatives to existing prediction methods, we have
      developed several tools in the statistical package R. ModuleFinder identifies
      sets of genes and treatments that we have found to form valuable sets for
      analysis of the mechanisms underlying gene co-expression. CoReg then links the
      hierarchical clustering of these co-expressed sets with frequency tables of
      promoter elements. These promoter elements can be drawn from known elements or
      all possible combinations of nucleotides in an element of various lengths. These
      sets of promoter elements represent putative cis-acting regulatory elements
      common to sets of co-expressed genes and can be prioritised for experimental
      testing. We have used these new tools to analyze the response of transcripts for
      nuclear genes encoding mitochondrial proteins in Arabidopsis to a range of
      chemical stresses. ModuleFinder provided a subset of co-expressed gene modules
      that are more logically related to biological functions than did subsets derived
      from traditional hierarchical clustering techniques. Importantly ModuleFinder
      linked responses in transcripts for electron transport chain components, carbon
      metabolism enzymes and solute transporter proteins. CoReg identified several
      promoter motifs that helped to explain the patterns of expression observed.
      CONCLUSION: ModuleFinder identifies sets of genes and treatments that form useful
      sets for analysis of the mechanisms behind co-expression. CoReg links the
      clustering tree of expression-based relationships in these sets with frequency
      tables of promoter elements. These sets of promoter elements represent putative
      cis-acting regulatory elements for sets of genes, and can then be tested
      experimentally. We consider these tools, both built on an open source software
      product to provide valuable, alternative tools for the prioritisation of promoter
      elements for experimental analysis.

PMID- 16606470
TI  - Differential activation of inflammatory pathways in A549 type II pneumocytes by
      Streptococcus pneumoniae strains with different adherence properties.
AB  - BACKGROUND: Adherence of Streptococcus pneumoniae bacteria to lung cells is a
      first step in the progression from asymptomatic carriage to pneumonia. Adherence
      abilities vary widely among S. pneumoniae patient isolates. In this study, the
      binding properties of S. pneumoniae isolates and the effects of binding on
      activation of the Nuclear Factor-Kappa-B (NFkappaB) pathway and cytokine
      secretion by type II pneumocytes were measured. METHODS: Mechanisms of high- and
      low-binding S. pneumoniae adherence to A549 cells were investigated by blocking
      putative receptors on bacteria and host cells with antibody and by eluting
      choline-binding proteins off of bacterial surfaces. NFkappaB activation was
      measured by western blot and immunocytochemistry and cytokine secretion was
      detected by a protein array. RESULTS: This study shows that S. pneumoniae
      isolates from pneumonia patients (n = 298) can vary by as much as 1000-fold in
      their ability to bind to human lung epithelial cells. This difference resulted in
      differential activation of the NFkappaB pathway. High-, but not low-binding S.
      pneumoniae used Choline-binding protein A (CbpA) to bind to complement component
      C3 on epithelial cell surfaces. Interleukin-8 (IL-8) was the only cytokine
      secreted by cells treated with either low- or high-binding S. pneumoniae.
      CONCLUSION: These results indicate that S. pneumoniae clinical isolates are not
      homogeneous in their interaction with host epithelial cells. The differential
      activation of host cells by high- and low-binding S. pneumoniae strains could
      have implications for the treatment of pneumococcal pneumonia and for vaccine
      development.

PMID- 16606471
TI  - Minimally invasive 'step-up approach' versus maximal necrosectomy in patients
      with acute necrotising pancreatitis (PANTER trial): design and rationale of a
      randomised controlled multicenter trial [ISRCTN13975868].
AB  - BACKGROUND: The initial treatment of acute necrotizing pancreatitis is
      conservative. Intervention is indicated in patients with (suspected) infected
      necrotizing pancreatitis. In the Netherlands, the standard intervention is
      necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In
      recent years several minimally invasive strategies have been introduced. So far,
      these strategies have never been compared in a randomised controlled trial. The
      PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived
      to yield the evidence needed for a considered policy decision. METHODS/DESIGN: 88
      patients with (suspected) infected necrotizing pancreatitis will be randomly
      allocated to either group A) minimally invasive 'step-up approach' starting with
      drainage followed, if necessary, by videoscopic assisted retroperitoneal
      debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both
      procedures are followed by CPL. Patients will be recruited from 20 hospitals,
      including all Dutch university medical centres, over a 3-year period. The primary
      endpoint is the proportion of patients suffering from postoperative major
      morbidity and mortality. Secondary endpoints are complications, new onset sepsis,
      length of hospital and intensive care stay, quality of life and total (direct and
      indirect) costs. To demonstrate that the 'step-up approach' can reduce the major
      morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total
      sample size of 88 patients was calculated. DISCUSSION: The PANTER-study is a
      randomised controlled trial that will provide evidence on the merits of a
      minimally invasive 'step-up approach' in patients with (suspected) infected
      necrotizing pancreatitis.

PMID- 16606472
TI  - WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian
      carcinoma: an immunohistochemical study.
AB  - BACKGROUND: WT1 is a tumor suppressor gene responsible for Wilms' tumor. WT1
      reactivity is limited to ovarian serous carcinomas. Recent studies have shown
      that WT1 plays an important role in the progression of disease and indicates a
      poorer prognosis of human malignancies such as acute myeloid leukemia and breast
      cancer. The aims of this study were to determine the survival and recurrence-free
      survival of women with advanced serous epithelial ovarian carcinoma in relation
      to WT1 gene expression. METHODS: The study accrued women over an 18-year period,
      from 1987-2004. During the study period, 163 patients were diagnosed with
      advanced serous epithelial ovarian carcinoma and had undergone complete post
      operative chemotherapy, but the final study group comprised 99 patients. The
      records of these women were reviewed and the paraffin-embedded tissue of these
      women stained with WT1 immunostaining. Survival analysis was performed using
      Kaplan-Meier and Cox regression methods. RESULTS: Fifty patients showed WT1
      staining and forty-nine did not. Five-year survival of non-staining and staining
      groups were 39.4% and 10.7% (p < 0.00005); five-year recurrence-free survival of
      these groups were 29.8% and < or = 7.5% (p < 0.00005), respectively. For survival
      the HR of WT1 staining, adjusted for residual tumor and chemotherapy response,
      was 1.98 (95% CI 1.28-3.79), and for recurrence-free survival the HR was 3.36
      (95% CI 1.60-7.03). The HR for recurrence-free survival was not confounded by any
      other variables. CONCLUSION: This study suggests that expression of WT1 gene may
      be indicative of an unfavorable prognosis in patients with advanced serous
      epithelial ovarian carcinoma.

PMID- 16606473
TI  - Doxycycline plus streptomycin versus ciprofloxacin plus rifampicin in spinal
      brucellosis [ISRCTN31053647].
AB  - BACKGROUND: The optimal treatment regimen and duration of the therapy is still
      controversial in spinal brucellosis. The aim of this study is to compare the
      efficacy, adverse drug reactions, complications and cost of ciprofloxacin plus
      rifampicin versus doxycycline plus streptomycin in the treatment of spinal
      brucellosis. METHODS: The patients diagnosed as spinal brucellosis between
      January 2002 to December 2004 were enrolled into the study. Patients were
      enrolled into the two antimicrobial therapy groups (doxycycline plus streptomycin
      vs. ciprofloxacin plus rifampicin) consecutively. For the cost analysis of the
      two regimens, only the cost of antibiotic therapy was analysed for each patient.
      RESULTS: During the study period, 31 patients with spinal brucellosis were
      enrolled into the two antimicrobial therapy groups. Fifteen patients were
      included in doxycycline plus streptomycin group and 16 patients were included in
      ciprofloxacin plus rifampicin group. Forty-two levels of spinal column were
      involved in 31 patients. The most common affected site was lumbar spine (n = 32,
      76%) and involvement level was not different in two groups. Despite the
      disadvantages (older age, more prevalent operation and abscess formation before
      the therapy) of the patients in the ciprofloxacin plus rifampicin group, the
      duration of the therapy (median 12 weeks in both groups) and clinical response
      were not different from the doxycycline plus streptomycin. The cost of
      ciprofloxacin plus rifampicin therapy was 1.2 fold higher than the cost of
      doxycycline plus streptomycin therapy. CONCLUSION: Classical regimen (doxycycline
      plus streptomycin), with the appropriate duration (at least 12 weeks), is still
      the first line antibiotics and alternative therapies should be considered when
      adverse drug reactions were observed.

PMID- 16606474
TI  - The impact of an hematocrit of 20% during normothermic cardiopulmonary bypass for
      elective low risk coronary artery bypass graft surgery on oxygen delivery and
      clinical outcome--a randomized controlled study [ISRCTN35655335].
AB  - INTRODUCTION: Cardiopulmonary bypass (CPB) induces hemodilutional anemia, which
      frequently requires the transfusion of blood products. The objective of this
      study was to evaluate oxygen delivery and consumption and clinical outcome in low
      risk patients who were allocated to an hematocrit (Hct) of 20% versus 25% during
      normothermic CPB for elective coronary artery bypass graft (CABG) surgery.
      METHODS: This study was a prospective, randomized and controlled trial. Patients
      were subjected to normothermic CPB (35 to 36 degrees C) and were observed until
      discharge from the intensive care unit (ICU). Outcome measures were calculated
      whole body oxygen delivery, oxygen consumption and clinical outcome. A
      nonparametric multivariate analysis of variance for repeated measurements and
      small sample sizes was performed. RESULTS: In a total of 54 patients (25% Hct, n
      = 28; 20% Hct, n = 26), calculated oxygen delivery (p = 0.11), oxygen consumption
      (p = 0.06) and blood lactate (p = 0.60) were not significantly different between
      groups. Clinical outcomes were not different between groups. CONCLUSION: These
      data indicate that an Hct of 20% during normothermic CPB maintained calculated
      whole body oxygen delivery above a critical level after elective CABG surgery in
      low risk patients. The question of whether a transfusion trigger in excess of 20%
      Hct during normothermic CPB is still supported requires a larger prospective and
      randomized trial.

PMID- 16606475
TI  - Long-term outcomes and clinical predictors of hospital mortality in very long
      stay intensive care unit patients: a cohort study.
AB  - INTRODUCTION: Little information is available on prognosis and outcomes of very
      long stay intensive care unit (ICU) patients. The purpose of this study was to
      identify long-term outcomes after hospital discharge and readily available
      clinical predictors of hospital mortality for patients requiring prolonged care
      in the ICU. METHOD: Clinical data were collected from consecutive patients
      requiring at least 30 days of ICU care admitted over 3 calendar years (2001 to
      2003) to a medical/surgical ICU in a university-affiliated tertiary care centre.
      RESULTS: A total of 182 patients met the inclusion criteria, with a mean age of
      63 years, median ICU stay of 48.5 days (interquartile range 36-78 days) and ICU
      mortality of 32%. They accounted for 8% of total admissions and 48% of total
      occupied beds. Of these patients, 42% died in hospital, 44% returned to their
      previous place of residence, and 14% were transferred to long-term care
      institutions. By 6 months after hospital discharge a further 8% of the patients
      had died, 40% remained at their previous place of residence, and 10% were in long
      term care. Predictors of hospital mortality, identified using multivariate
      logistic regression, included age (odds ratio [OR] 1.45 per additional decade,
      95% confidence interval [CI] 1.10-1.91), any immunosuppression (OR 5.2, 95% CI
      1.7-15.5), mechanical ventilation for longer than 90 days (OR 4.0, 95% CI 1.3
      12.0), treatment with inotropes or vasopressors for more than 3 days at or after
      day 30 in the ICU (OR 7.1, 95% CI 2.6-19.3), and acute renal failure requiring
      dialysis at or after day 30 in the ICU (OR 6.3, 95% CI 2.0-19.7). CONCLUSION:
      Patients with very long stays in the ICU appear to have a reasonable chance of
      survival, with most survivors in our cohort residing at their previous place of
      residence 6 months after hospital discharge. Prolonged requirement for life
      support therapies (ventilation, vasoactive agents, or acute dialysis) and a
      limited number of pre-existing co-morbidities (immunosuppression and, to a lesser
      extent, patient age) were predictors of increased hospital mortality. These
      predictors may assist in clinical decision making for this resource intensive
      patient population, and their reproducibility in other very long stay patient
      populations should be explored.

PMID- 16606476
TI  - The value of monitoring outcomes should be measured by the appropriateness of the
      response.
AB  - Real-time monitoring of outcomes is becoming increasingly feasible in health
      care, and with it the hope of early detection of problems and the ability to tell
      whether interventions are having their desired effect. The next step should be to
      try to demonstrate that the reports of such monitoring systems lead to reasonable
      responses and valid inferences about causality, and that we are not chasing red
      herrings.

PMID- 16606477
TI  - How similar are fluid cognition and general intelligence? A developmental
      neuroscience perspective on fluid cognition as an aspect of human cognitive
      ability.
AB  - This target article considers the relation of fluid cognitive functioning to
      general intelligence. A neurobiological model differentiating working
      memory/executive function cognitive processes of the prefrontal cortex from
      aspects of psychometrically defined general intelligence is presented. Work
      examining the rise in mean intelligence-test performance between normative
      cohorts, the neuropsychology and neuroscience of cognitive function in typically
      and atypically developing human populations, and stress, brain development, and
      corticolimbic connectivity in human and nonhuman animal models is reviewed and
      found to provide evidence of mechanisms through which early experience affects
      the development of an aspect of cognition closely related to, but distinct from,
      general intelligence. Particular emphasis is placed on the role of emotion in
      fluid cognition and on research indicating fluid cognitive deficits associated
      with early hippocampal pathology and with dysregulation of the hypothalamic
      pituitary-adrenal axis stress-response system. Findings are seen to be consistent
      with the idea of an independent fluid cognitive construct and to assist with the
      interpretation of findings from the study of early compensatory education for
      children facing psychosocial adversity and from behavior genetic research on
      intelligence. It is concluded that ongoing development of neurobiologically
      grounded measures of fluid cognitive skills appropriate for young children will
      play a key role in understanding early mental development and the adaptive
      success to which it is related, particularly for young children facing social and
      economic disadvantage. Specifically, in the evaluation of the efficacy of
      compensatory education efforts such as Head Start and the readiness for school of
      children from diverse backgrounds, it is important to distinguish fluid cognition
      from psychometrically defined general intelligence.

PMID- 16606498
TI  - Money as tool, money as drug: the biological psychology of a strong incentive.
AB  - Why are people interested in money? Specifically, what could be the biological
      basis for the extraordinary incentive and reinforcing power of money, which seems
      to be unique to the human species? We identify two ways in which a commodity
      which is of no biological significance in itself can become a strong motivator.
      The first is if it is used as a tool, and by a metaphorical extension this is
      often applied to money: it is used instrumentally, in order to obtain
      biologically relevant incentives. Second, substances can be strong motivators
      because they imitate the action of natural incentives but do not produce the
      fitness gains for which those incentives are instinctively sought. The classic
      examples of this process are psychoactive drugs, but we argue that the drug
      concept can also be extended metaphorically to provide an account of money
      motivation. From a review of theoretical and empirical literature about money, we
      conclude that (i) there are a number of phenomena that cannot be accounted for by
      a pure Tool Theory of money motivation; (ii) supplementing Tool Theory with a
      Drug Theory enables the anomalous phenomena to be explained; and (iii) the human
      instincts that, according to a Drug Theory, money parasitizes include trading
      (derived from reciprocal altruism) and object play.

PMID- 16606523
TI  - Cricotracheal separation: a review and a case with bilateral recovery of
      recurrent laryngeal nerve function.
AB  - Cricotracheal separation (CTS) is an uncommon injury, with a high index of
      suspicion required to establish the diagnosis. Computerized tomography (CT) plays
      a role in diagnosis but cannot necessarily be relied upon. Bilateral recurrent
      laryngeal nerve (RLN) palsies are usually associated with this type of injury. We
      recently treated a patient with CTS in whom one RLN was intact from the time of
      the injury and the other nerve recovered within three months. Computed tomography
      was inconclusive. Early open repair of the injury and frequent follow-up
      examinations led to successful decannulation after six weeks and excellent short
      term voice and airway outcomes. A detailed discussion of this unusual case is
      followed by a review of the current literature on CTS, with particular emphasis
      on significant management dilemmas and controversies. Clinical suspicion remains
      more sensitive than investigations in diagnosing CTS. Permanent bilateral RLN
      palsies are not inevitable following these injuries.

PMID- 16606525
TI  - [Research and practice of antibiotic strategies for controlling and avoiding
      bacterial resistance].

PMID- 16606526
TI  - [How to evaluate the clinical significance of causative organism culture and drug
      susceptibility test for a clinician].

PMID- 16606527
TI  - [How to achieve the global protection of traditional Chinese medicine].

PMID- 16606528
TI  - [Changes of antimicrobial resistance among clinical isolates of Escherichia coil
      in Shanghai 1990-2004].
AB  - OBJECTIVE: To investigate the trend of resistance to antimicrobial agents among
      clinical isolates of Escherichia coli 1990-2004. METHODS: Agar diffusion test was
      used to analyze the changes of drug susceptibility of 33,495 strains of E. coli
      isolated from 11 hospitals in Shanghai to 21 antimicrobial agents 1990-2004.
      RESULTS: The resistance rates of 33,495 E.coli isolates to 21 antimicrobial
      agents mostly increased 1990-2004. The resistance rates to ampicillin and
      piperacillin increased from 69% and 30% to 85% and 71.4% respectively. The
      resistance rates to cephalosporins, except ceftazidime and cefepime, all
      increased, e. g., the resistance rates to cefazolin (24.0%-->48.3%), cefuroxime
      (18.0%-->45.7%), and cefaclor (33.3%-->46.8%), especially that to cefotaxime
      (6.0%-->35.2%). The resistance rate to fluoroquinolones increased from 11.0% to
      55.4%. The resistance rate to gentamicin increased from 44.0% to 54.0%. The
      resistance rates to tetracycline, chloramphenicol, SMZ/TMP remained at high
      levels. However, ceftazidime, cefepime, imipenem, amikacin, beta-lactams/beta
      lactamase inhibitors, and nitrofurantoin remained active against the E.coli
      isolates. The detectable rate of extended-spectrum beta-lactamase-producing
      strains in E. coli increased from 14.7% to 36.5%. CONCLUSION: The trend of
      resistance of E. coli to commonly used antimicrobials was upward 1990-2004.

PMID- 16606529
TI  - [Molecular mechanism of multiple-drug and pan-drug resistance among Acinetobacter
      species].
AB  - OBJECTIVE: To investigate the molecular mechanism of multiple-drug and pan-drug
      resistance among Acinetobacter species. METHODS: Non-repetitive 90 carbapenem
      resistant strains of Acinetobacter species were collected in Beijing, Guangzhou,
      and Fuzhou 1999-2004. The homology of the isolates was determined by both pulsed
      field gel electrophoresis and randomly amplified polymorphic DNA typing. Seven
      representative clones were selected from the 90 strains of Acinetobacter isolated
      from different hospitals to be used for further study. Analytical isoelectric
      focusing was used to measure the isoelectric point of the beta-lactamase. Plasmid
      DNA was extracted and purified Genes of different beta-lactamase, including
      bla(TEM--), bla(SHV-), bla(PER-), blaI(MP-), bla(VIM-), and bla(OXA-) genes, in
      these clone strains were amplified and sequenced. PCR was used to analyze the
      integrons. RESULTS: The P clone strain isolated during an outbreak of pan-drug
      resistant Acinetobacter species in Peking Union Medical College Hospital 2004 was
      not susceptible to most common antimicrobial agents tested. The 7 representative
      clones produced multiple beta-lactamases: TEM-1, high-level AmpC, SHV-type, OXA
      23 carbapenemase and IMP-8 and metalloenzyme respectively. One clone produced PER
      1 enzyme. These 7 clone strains were resistant to most beta-lactams (including
      carbapenems), erythromycin, chloramphenicol, and rifampin. Two clone strains were
      susceptible to cefoperazone/sulbactam and amikacin while 4 clone strains
      susceptible to levofloxacin. All of the 7 clones were susceptible to minocycline
      and colistin. Five different integrons were found, harboring the genes mediating
      the resistance to aminoglycosides, rifampin, chloramphenicol, and carbapenems
      (bla(IMP-8)). CONCLUSION: The molecular bases of multiple-drug or pan-drug
      resistance in Acinetobacter species include production of OXA-23 carbapenemase or
      IMP type metalloenzyme and integrons with different resistance gene cassettes.
      Pan-drug-resistant Acinetobacter species are susceptible to old antimicrobials
      agents, such as colistin and minocycline.

PMID- 16606530
TI  - [Indications of arterial switch operation for complex congenital heart defect
      with severe pulmonary hypertension and ventriculoarterial discordant connection].
AB  - OBJECTIVE: To summarize the experience in arterial switch operation (ASO) for
      complex congenital heart defect (CHD) with severe pulmonary hypertension (PH) and
      ventriculoarterial discordant connection in children older than 6 months.
      METHODS: Twenty-three consecutive pediatric patients suffering from severe CHD,
      such as transposition of great arteries (TGA), Taussing-Bing anomaly, etc, with
      moderate to severe PH, 15 male and 8 female, aged 7-84 months, with the body
      weight of 4.5-20.0 kg, pulmonary pressure of 24.0-80.0 mm Hg, and pulmonary
      resistance of 49.2-1261.9 dyn.s.cm(-5), and with different complication such as
      left ventricular outflow tract obstruction (3 cases), subpulmonary membrane (1
      case), and subaortic membrane (1 case), underwent ASO under general anesthesia
      and extracorporeal circulation with low temperature (18 degrees C-22 degrees C)
      and low volume blood flow (50 ml.kg(-1).min(-1)). The complicated anomalies were
      corrected simultaneously. Nitric oxide and alpha-blocker were used to the
      children with PH during the peri-operational period. RESULTS: Twenty children
      survived, and were cured and discharged with an obvious improvement of heart
      function, only one of which had sequel of coma due to cerebral anoxia. After
      operation the pulmonary pressure decreased to 23 mm Hg +/- 9 mm Hg, significantly
      lower than that before operation (P = 0.000). Physical activities increased
      obviously. Three children died post-operatively of the reasons un-related to the
      pre-operative PH and pulmonary arterial resistance, with a mortality of 13.04%.
      Follow-up of 14 +/- 8 months showed no death and complication. CONCLUSION: ASO
      can still realize satisfactory early results for the children older than 6 months
      suffering from complex CHD with moderate to severe PH and ventriculoarterial
      discordant connection provided they are in a rather good condition without severe
      cyanosis (SaO(2) > 60%) and with the pulmonary arterial resistance being
      acceptable (pressure of right atrium < 1000 dyn.s.cm(-5)).

PMID- 16606531
TI  - [Expression of non-T cell derived cytokines in acute rejection after heart
      transplantation: experiment with mouse model].
AB  - OBJECTIVE: To investigate the expression of non-T cell derived cytokines in acute
      rejection after heart transplantation. METHODS: The hearts of 26 C57BL/6 mice
      were transplanted into the abdominal cavities of 26 Balb/c mice (acute rejection
      group). The hearts of 26 Balb/c mice were transplanted into the abdominal
      cavities of another 26 Balb/c mice (syngeneic control group). After the
      operation, heart beat was felt with finger at the abdomen every day to determine
      the survival of the transplanted heart. One, three, five, and seven days after
      the operation the transplanted hearts were taken out from 5 mice in each group
      respectively to undergo microscopy. RT-PCR was used to detect the mRNA expression
      of these cytokines: interleukin (IL)-2, IL-15, tumor necrosis factor (TNF)-alpha,
      and interferon (IFN)-gamma. Western blotting was used to detect the protein
      expression of these cytokines. Six mice in each group, totally 12, were used to
      observe the survival time of transplanted heart. RESULTS: The mice of the control
      group recovered more rapidly in comparison with the nice of the acute rejection
      group. The survival times of the transplanted hearts of the control group were
      all longer than 100 days, significantly longer than those of the acute rejection
      group (7-9 days, P < 0.01). No sign of acute rejection was found in the hearts of
      the control group, and significant lymphocyte infiltration was seen in the
      myocardium of the acute rejection group 3-7 days after the operation. In the
      control group, no mRNA expression of IL-2 and IFN-was seen at any time-point, and
      IL-15 mRNA and TNF-alpha mRNA were expressed at low level at any time-point.
      However, in the acute rejection group the mRNA expression of IL-2, TNF-alpha, and
      IL-15 could be detected since the first day post-operatively and peaked on the
      day 5, but the mRNA expression of IFN-gamma could be detected and peaked only on
      the 5 th post-operative day. The mRNA expression levels of these 4 cytokines at
      any time point of the acute rejection group were all significantly higher than
      those of the control group (P < 0.01 or P < 0.05). The proteins of the 4
      cytokines were all expressed at low level at any time point in the control group.
      However, in the acute rejection group the protein expression levels of IL-15 and
      IL-2 began to increase since the third day after operation and the protein
      expression levels of TNF-alpha and IFN-gamma began to increase since the first
      day after operation. CONCLUSION: Many cytokines, including T cell derived and non
      T cell derived cytokines, are involved in the pathogenesis of acute rejection
      after allogeneic organ transplantation.

PMID- 16606532
TI  - [Mechanism of relaxation mediated by nitric oxide on human lower esophageal
      sphincter].
AB  - OBJECTIVE: To explore the mechanism of relaxation mediated by nitric oxide on the
      human lower esophageal sphincter (LES), and compare the difference in relaxation
      response between clasp fibers and sling fibers. METHODS: 32 LES specimens were
      obtained from 32 patients with high-positioned carcinoma of the mid-esophagus, 12
      males and 16 females, aged 55.9 +/- 9.3, during operation. The clasp fibers and
      sling fibers were isolated and suspended in perfusion tough. Electric field
      stimulation (EFS) was applied to the clasp and sling fibers in vitro. Nitric
      oxide synthase (NOS) inhibitor L-NNA, NOS substrate L-arginine, neurotoxin
      tetrodotoxin (TTX), and atropine were added respectively to observe their effects
      on the clasp and sling fibers under EFS. Sodium nitroprusside was added on the
      two kinds of smooth muscle stripes to observe its influence as well. RESULTS: EFS
      induced frequency-dependent relaxation to clasp fibers and some of sling fibers,
      which was inhibited by L-NNA in a concentration-dependent manner and was reversed
      by L-arginine partially. Maximal relaxation in clasp fibers and sling fibers was
      observed at 512 Hz and 16 Hz respectively. The higher amplitude relaxation was
      induced in the sling fibers at lower stimulus frequencies (< 32 Hz). Conversely,
      the same response was induced in the clasp fibers at higher stimulus frequencies
      (> 64 Hz). Meanwhile, off-contraction was induced by EFS in some sling fibers and
      clasp fibers. In some sling fibers, contraction was induced by EFS which was
      inhibited by atropine. Maximal contraction in these fibers was observed at 128
      Hz. TTX abolished the effect of EFS on both clasp and sling fibers, which was
      considered neurogenic. Sodium nitroprusside elicited the similar response to EFS.
      CONCLUSIONS: Relaxation of clasp and sling fibers is related to L-NNA, TTX, and
      sodium nitroprusside, and can be mediated by nitric oxide. Lower stimulus
      frequencies induce higher amplitude relaxation to sling fibers, and conversely,
      higher stimulus frequencies induce higher amplitude relaxation to clasp fibers.
      EFS induces contraction response in some sling fibers.

PMID- 16606533
TI  - [The role of CD4+ CD25+ regulatory T cells in the pathogenesis of asthma in
      children].
AB  - OBJECTIVE: To investigate the role of CD4(+)CD25(+) regulatory T cells (Tr cells)
      in the pathogenesis of asthma in children. METHODS: Peripheral blood samples were
      collected from 20 pediatric patients with asthma, 10 male and 10 female, aged 7
      (3-12), and 20 healthy children, 10 male and 10 female, aged 6.5 (2-11).
      Lymphocytes were isolated. Flow cytometry was used to examine the percentages of
      CD4(+)CD25(+) regulatory T cells, IL-10 secreting CD4(+)CD25(+) regulatory T
      cells (CD4(+)CD25(+)-IL-10), and transforming growth factor (TGF)-beta secreting
      CD4(+)CD25(+) regulatory T cells (CD4(+)CD25(+)-TGF-beta). RT-PCR and real-time
      PCR were used to detect the mRNA expression of suppressor of cytokine signal 1
      (SOSC1) and Foxp3. RESULTS: The percentages of CD4(+)CD25(+) regulatory T cells
      of the asthma children was 6.51% +/- 1.94%, significantly lower than that of the
      healthy children (11.96% +/- 2.30%, P < 0.01); the percentage of CD4(+)CD25(+)-IL
      10 of the asthma children was 1.46% +/- 0.35%, significantly lower than that of
      the healthy children (5.65% +/- 1.70%, P < 0.01); and the percentage of
      CD4(+)CD25(+)-TGF-beta of the asthma children was 1.24% +/- 0.21%, significantly
      lower than that t of the healthy children (4.23% +/- 1.65%, P < 0.01). The Foxp3
      mRNA expression of the asthma children was 0.12 +/- 0.05, significantly lower
      than that of the healthy children (1.71 +/- 0.58, P < 0.01); and the SOCS1 mRNA
      expression of the asthma children was 0.38 +/- 0.19, significantly lower than
      that of the healthy children (1.51 +/- 0.41, P < 0.01). CONCLUSION: The decrease
      of CD4(+)CD25(+) regulatory T cells may be involved in the pathogenesis of
      asthma. The decreased mRNA expression of Foxp3 and SOCS1 may be associated with
      the aberrant development of CD4(+)CD25(+) regulatory T cells.

PMID- 16606534
TI  - [Etiology, diagnosis and management of spontaneous per renal hemorrhage].
AB  - OBJECTIVE: To investigate the etiology, diagnosis, and management of spontaneous
      perirenal hemorrhage (SPH). METHODS: The clinical data of 35 patients, 10 males
      and 12 females, aged 35.9 (12-77), with the diagnosis of SPH, without history of
      trauma, anticoagulant use, dialysis, and renal transplantation, were analyzed.
      RESULTS: The underlying disease of SPH included angiomyolipoma (18 cases), renal
      cell carcinoma (7 cases), kidney cyst (2 cases), renal artery aneurysm (3 cases),
      rupture of renal artery aneurysm accompanied with pregnancy (2 cases), renal
      pheochromocytoma (3 cases 2 of which accompanied with pregnancy), congenital
      stricture of pelvic ureter junction (1 case), and liver cancer (1 case). The most
      common underlying diseases were nephrogenic (96%) with angiomyolipoma ranking
      first (54%) followed by renal cell carcinoma (21%). The underlying diseases were
      diagnosed correctly in 23 cases (69%). CT helped in diagnosis of 34 cases.
      Surgery was performed on most of the cases. CONCLUSION: The most common causes of
      SPH is renal neoplasms more than 50% of which are benign. Renal artery aneurysm
      and pheochromocytoma tend to rupture during pregnancy. CT is the first method of
      choice in diagnosis.

PMID- 16606535
TI  - [Laparoscopic aid in upper urinary reconstructive operation].
AB  - OBJECTIVE: To evaluate the efficacy and feasibility of laparoscopic aid in upper
      urinary reconstructive operation. METHODS: Fifty-eight patients with
      ureteropelvic junction obstruction, 5 patients with upper ureter polypous, 2
      patients with upper ureter stenosis, and 13 patients with upper ureter lithiasis
      underwent upper urinary reconstructive operation with laparoscopic aid described
      as follows:an incision 1 cm long was made, a 10 mm trocar and a 30 degrees
      laparoscope were wt in, the part with lesion was isolated and resected, and then
      pyeloplasty or end-to-end anastomosis of ureter was performed. RESULTS: The mean
      operative time was 33 minutes (25-45 minutes). The mean blood loss was 20 ml (15
      25 ml). Complications such as urinary leakage and infection were observed. The
      double J stent was removed at 1 month after the operation. Follow-up for 3 to 15
      months in 20 cases showed alleviation of hydronephrosis. CONCLUSION: An effective
      and safe method with less wound and operative time, combination of laparoscopic
      aid and open surgery in upper urinary reconstructive operation helps avoid
      difficult laparoscopic operation, does not increase trauma of the abdominal wall,
      and is worth promoting clinically.

PMID- 16606537
TI  - [Application of hydroxyapatite in micro-otosurgery: experiment with guinea pigs
      and clinical application].
AB  - OBJECTIVE: To investigate the feasibility of hydroxyapatite (HA) middle ear
      prostheses in otosurgery. METHODS: In the animal experiment HA prostheses were
      put in the bilateral bullae of the ears of 12 healthy white guinea pigs (totally
      24 ears). Three guinea pigs were killed every month 1-4 months later.
      Morphological examination and electron microscopy were conducted to observe
      grafts. In the clinical experiment HA prostheses was used in ossiculoplasty in 31
      cases, reconstruction of posterior wall of external auditory canal in 5 cases,
      and mastoid obliteration in 11 cases. RESULTS: The HA prostheses taken out from
      23 ears of the guinea pigs were with normal and complete structure, and clear
      margin in gross anatomy and microscopically. Only one ear suffered infection.
      Follow-up or the patients for 1-4 years showed excellent healing of the operated
      parts and an improvement of hearing threshold by about 16 dBHL. CONCLUSION:
      Hydroxyapatite with excellent physical and chemical properties and biological
      tolerance HA is a good material in ossiculoplasty, canaloplasty, mastoid
      obliteration, and other otological operations.

PMID- 16606538
TI  - [Adjustment of dose-response relationship of industrial impulse noise induced
      high frequency hearing loss with different exchange rate].
AB  - OBJECTIVE: To explore a new method to evaluate the dose-response relationship
      between the noise exposure and prevalence of noise induced high frequency hearing
      loss. METHODS: Physical examination and questionnaire survey were conducted among
      32 mechanical workers, 12 males and 20 females, aged 35.1 +/- 7.2, exposed to
      industrial impulse noise (impulse noise group), and 163 textile workers, 82 males
      and 81 females, aged 31.5 +/- 8.7, exposed continuous noise (continuous noise
      group). SH-126 dosimeter was used to measure the A weighted equal sound level in
      continuous eight working hours (L(Aeq.8h)) so as to evaluate the individual noise
      exposure. Cumulative noise exposure (CNE) was calculated with the values of
      L(Aeq.8h) and noise working year adjusted by different exchange rates (ERs) for
      each worker. Hearing threshold was measured by audiometer with routine method and
      adjusted by age and gender according to GBZ49-2002. High frequency hearing loss
      was diagnosed based on the GBZ49-2002 for each worker. RESULTS: According to the
      equal energy rule, with the ER = 3 the CNE of the impulse noise group was [103.2
      dB (A).year +/- 4.2dB (A).year], significantly lower than that of the continuous
      noise group [110.6 +/- 6.0 dB (A).year, P < 0.05]. With the ER = 5.5, the CNE of
      the impulse noise group was 110.3 +/- 6.6 dB (A).year, not significantly
      different from that of the continuous noise group [110.6 +/- 6.0 dB (A).year].
      The high frequency hearing loss prevalence of the impulse noise group was 68.8%,
      not significantly different that of the continuous noise group (65%, P > 0.05).
      Trend chi square test showed significant differences in the relationship between
      CNE and hearing loss prevalence among the impulse noise group with the ER = 3,
      the impulse noise group with the ER = 5.5, and continuous noise group (all P <
      0.01). With the ER = 3, the high frequency hearing loss prevalence of the impulse
      noise group with the CNE of 100-104 dB (A).year was 76.9%, significant higher
      than that of the continuous noise group (30.4%, P < 0.05); and the high frequency
      hearing loss prevalence of the impulse noise group with the CNE of 105-108 dB
      (A).year was 90.9%, significantly higher than that of the continuous noise group
      (50.0%, P < 0.05). With the ER = 5.5, there was no difference in the prevalence
      of high frequency hearing loss between the continuous noise group and impulse
      noise group. Logistic regression model showed that with the ER = 3, the dose
      response curve of the impulse noise group presented a left shift and with a slope
      sharper than that of the continuous noise group. With the ER increasing the dose
      response curve of the impulse noise group showed a right shift and with a
      gradually lowering slope. When the ER equaled to 6 in the impulse noise group and
      equaled to 3 in the continuous noise group, the two dose-response curves were
      almost superposed. CONCLUSION: Impulse noise causes more serious damage in
      causing high frequency hearing loss than continuous noise according to equal
      energy rule. Increasing the ER value in the impulse noise group adjusts the dose
      response curve to be close to that of the continuous noise group.

PMID- 16606539
TI  - [Management and risk factors of recurrent gestational trophoblastic tumor].
AB  - OBJECTIVE: To analyze the management, prognosis and prognostic risk factors of
      recurrent gestational trophoblastic tumor (GTT). METHODS: One thousand one
      hundred and thirty GTT patients, aged 29 +/- 6, were hospitalized and treated and
      901 of them got complete remission (CR). Among these CR patients, 31 suffered
      relapsed. The clinical data of these 31 cases were analyzed retrospectively.
      RESULTS: Thirty-one patients suffered 15.3 months (6-72 months) after the
      cessation of treatment with an overall recurrence rate of 3.4% (31/901). Four of
      the 31 patients suffered relapse repeatedly (totally seven times), resulting in
      an overall re-recurrence rate of 22.6% (7/31). Twenty-five of the 31 patients
      were re-hospitalized and received treatment. Eighteen of them got complete
      remission (CR), 3 got partial remission (PR), and 4 died of progress of the
      disease (PD). The major adverse prognostic risk factors included: clinical stage
      (P < 0.05), an interval of more than 12 months from the antecedent pregnancy to
      chemotherapy (OR = 3.170, P < 0.05), declination of beta-hCG level back to normal
      titer after more than seven courses of chemotherapy (OR = 4.775, P < 0.05), and
      less than two courses of consolidation chemotherapy (OR = 0.441, P < 0.05).
      CONCLUSION: More attention should be given to those GTT patients with adverse
      prognostic risk factors. Multi-drug and multiple route chemotherapy and/or
      combined surgical intervention can be used to improve the cure rate and lower the
      re-recurrence rate of the GTT recurrent patients.

PMID- 16606540
TI  - [Expression of alpha-tubulin and gamma-tubulin in premalignant lesion and
      carcinoma of breast and the significance thereof].
AB  - OBJECTIVE: To investigate the expression of alpha-tubulin and gamma-tubulin, 2
      kinds of centrosome proteins, in premalignant lesion and carcinoma of breast and
      the significance thereof. METHODS: Forty specimens of premalignant lesions of
      breast, 40 specimens of infiltrating ductal carcinoma of breast, 40 specimens of
      intraductal carcinoma (IDC), and 30 specimens of normal breast tissues were
      obtained during operation. Immunohistochemistry was used to analyze the protein
      expression of alpha-tubulin and gamma-tubulin, and the percentages of ki67
      positive cells. Western blotting was used to examine the mRNA expression of alpha
      tubulin and gamma-tubulin. RESULTS: The protein and mRNA expression values of
      alpha-tubulin and gamma-tubulin in breast carcinoma were higher than those in the
      premalignant lesions and normal breast tissues with significant differences
      between the premalignant lesions and normal breast torques and without
      significant differences between infiltrating ductal carcinoma of breast and IDC.
      The ki67 positive rates of the infiltrating ductal carcinoma of breast group, IDC
      group, premalignant lesion group, and normal breast tissues group were 16.0%,
      37.0%, 53.6%, and 67.8% (P = 0.001). A positive correlation existed between the
      expression of alpha-tubulin and the expression of gamma-tubulin in the same case
      and the same group (all P = 0.00) and there was no significant correlation
      between the expression of alpha-tubulin and the expression of gamma-tubulin in
      the same case and the same group (all P > 0.05). Both the expression of alpha
      tubulin and the expression of gamma-tubulin were significantly associated with
      the prognosis. CONCLUSIONS: Centrosome protein is one of the distinct phenotypes
      of breast cancer cells. Aberration of centrosome proteins may be used to screen
      high risk cases of breast carcinoma and to estimate the prognosis.

PMID- 16606541
TI  - [Screening of a sub-clone of human breast cancer cells with high metastasis
      potential].
AB  - OBJECTIVE: To screen a sub-clone of human breast cancer cell of the MCF-7 line
      with high metastasis potential. METHODS: Human breast cancer cells of the MCF-7
      line were injected subcutaneously into 10 severe combined immunodeficiency (SCID)
      mice. Sixty-eight days after the mice were killed and their lungs were taken out.
      Primary cell culture was conducted. When the cells were passed on to the third
      generation a sub-clone was screened from the lung tissue and termed LM-MCF-7.
      Microscopy was performed on the lung tissues. The growth curve was drawn. Flow
      cytometry was used to examine the cell cycle. Chromosome analysis was done.
      Immunohistochemistry was used to detect the expression of breast cancer specific
      antigen CAI5-3. Western blotting was used to detect the protein expression of the
      protein associated with tumor metastasis: nm23 (a metastasis-suppressing gene),
      myosin light chain kinase (MLCK, a kinase related to cell movement), survivin,
      bcl-2 and p27 (a gene related to cell cycle). LM-MCF-7 cells were injected into
      other SCID mice and these mice were killed 30 days later to observe the
      metastasis of cancer so as to detect the tumorigenic ability of the LM-MCF-7
      cells. RESULTS: When the cells from the mouse lung tissues were passed on to the
      third generation a sub-clone with high metastasis potential was screened and
      termed LM-MCF-7. The morphology of the new cell line was typically epithelioid.
      Flow cytometry showed that the DNA relatively contents were 53.40% of the LM-MCF
      7 cells were in the G(0)/G(1) phase, a lower percentage than that of the MCF-7
      cells, and 17.10% in the S phase and 23.20% in the G(2+)M phase, both percentages
      higher than those of the MCF-7 cells. The proliferating time of the LM-MCF-7 cell
      population was about 20 +/- 14 hours, much shorter than that of the parent strain
      cells. The chromosomes of the LM-MCF-7 cells, numbering 16-123, showed the
      morphology characteristic c of human chromosomes. The marker of human breast
      cancer CA15-3 was detected in both MCF-7 and LM-MCF-7 cells. The protein
      expression of nm23 and p27 was down-regulated, but the protein expression of
      MLCK, bcl-2 and survivin was up-regulated in LM-MCF-7 cells in comparison with
      those in MCF-7 cells. The tumorigenesis rate of LM-MCF-7 cells was 100% (5/5),
      with a latent period of 5.0 +/- 0.0 d, and the tumor metastasized to lung,
      kidney, spleen, bone marrow, lymph node and heart. CONCLUSION: A human breast
      cancer line, LM-MCF-7 cell line, with high metastasis potential has been derived
      from the human breast cancer cells of MCF-7 line.

PMID- 16606544
TI  - Controversies in food allergy.

PMID- 16606545
TI  - Cow's milk protein allergy. A multi-centre study: clinical and epidemiological
      aspects.
AB  - BACKGROUND: Due to the age when it becomes apparent and the treatment needed,
      cow's milk proteins (CMP) allergy requires an accurate diagnosis to avoid
      labelling infants falsely as allergic and subjecting them to unnecessary diets.
      The objective of this multi-centre study carried out at the Allergy Units of 14
      Children's Hospitals was to discover the epidemiological, clinical and
      evolutionary characteristics of cow's milk protein allergy (CMPA). METHODS AND
      RESULTS: Infants suspected of CMPA who attended allergy clinics at the hospitals
      taking part during the study period were studied and a detailed clinical history
      was collected on all of them. Prick tests were done with cow's milk and its
      proteins and specific IgE anti-bodies were determined by means of CAP with the
      same allergens as the Prick test. The challenge test with cow's milk was carried
      out unless contraindicated by the diagnostic protocol. Two different challenge
      regimens were used: one of them carried out in 3 days and the other in one day.
      409 infants with suspected CMPA were included and the diagnostic challenge test
      was performed on 286 patients (70 %) and not carried out on 123, as it was not
      indicated according to the protocol. IgE-mediated allergy was confirmed in 234
      infants (58 %) and in 15 (4 %) non-IgE-mediated hypersensitivity was diagnosed.
      The two challenge regimens were equally secure. The average age when the reaction
      to cow's milk formula took place was 3.5 months (10 days-10 months). The symptoms
      appeared in the first week of introduction in 95 % of cases and appeared in 60 %
      with the first feeding with the formula. The most frequent clinical signs were
      cutaneous in 94 % of cases and the majority of cases appeared within 30 minutes
      of the feed. 99 % had been breast fed and 44 % had received some cow's milk
      supplement during the lactation period. Sensitization to egg not given in the
      feed was noted in 30 % and to beef in 29 %, being well tolerated in all of these.
      CONCLUSIONS: Carrying out an appropriate diagnostic protocol in infants attending
      for suspected CMPA allows allergy to be ruled out in a high percentage of cases.

PMID- 16606547
TI  - Allergy to pine processionary caterpillar (Thaumetopoea pityocampa) in children.
AB  - Contact with pine processionary caterpillar (Thaumetopoea pityocampa) induces
      dermatitis usually located in exposed areas through a toxic-irritative mechanism.
      Over the last few years an immediate hypersensitivity mechanism have mainly been
      demonstrated in adult patients. However, there are few studies carried out in
      children. OBJECTIVE: To evaluate a group of 16 children who experienced allergic
      reactions after exposure to pine processionary caterpillar. PATIENTS AND METHODS:
      All patients underwent allergy testing through skin prick test. Serum specific
      IgE determination was performed by EAST technique. The molecular mass of the IgE 
      binding bands was studied by SDS-PAGE Immunoblotting. RESULTS: Skin prick test
      with the caterpillar extract was positive in all patients. Specific IgE was
      positive (higher than 0.35 kU/L) in 15 patients' sera. Western blotting showed
      several IgE-binding bands with molecular mass values ranging from 17.5 to 168
      kDa. Electrophoretic mobility of some of the relevant allergens was related to
      the conditions of sample preparation (reduced or non-reduced). CONCLUSIONS: The
      results of this study demonstrate the existence of an allergic IgE-mediated
      mechanism caused by pine processionary caterpillar proteins. Airborne urticating
      hairs of this animal should be considered as seasonal inhalant allergen, which is
      able to induce allergic pathologies in children who frequent pine areas.

PMID- 16606546
TI  - Effectiveness of nebulized furosemide added to nebulized salbutamol in children
      with acute asthma.
AB  - BACKGROUND: Nebulized furosemide has been shown to be protective against
      bronchoconstricting stimuli. METHODS: To investigate whether inhaled furosemide
      would exhibit an additional therapeutic effect in children with acute asthma we
      performed a double-blind, placebo-controlled study in which patients with acute
      asthma attack were randomized to receive either nebulized salbutamol (0.15 mg/kg)
      plus nebulized furosemide (10 mg/m(2)) or nebulized salbutamol (0.15 mg/kg) plus
      nebulized saline as placebo. In all patients, clinical asthma scores (CAS) were
      determined before and after drug administration. Peak expiratory flow rates
      (PEFR) were measured by a peak flow meter. RESULTS: CAS and PEFR improved in both
      groups with nebulized salbutamol treatment. The CAS changed from 3.56 +/- 2.13 to
      2.06 +/- 1.84 (p = 0.0001) in the study group and from 4.44 +/- 2.63 to 2.56 +/-
      1.86 (p = 0.0003) in the control group. PEFR increased from 177.50 +/- 65.88 to
      221.88 +/- 66.05 L/min in the first group (p = 0.0001) and from 183.13 +/- 51.73
      to 218.13 +/- 60.25 in the second group (p = 0.0001). CONCLUSION: Adding
      nebulized furosemide to nebulized salbutamol in pediatric patients experiencing
      an acute asthma attack did not produce greater improvement in clinical (p =
      0.3829) or spirometric (p = 0.3839) parameters than nebulized salbutamol alone.

PMID- 16606548
TI  - Immunochemical comparison of the allergenic potency of spores and mycelium of
      Cladosporium cladosporioides extracts by a nitrocellulose electroblotting
      technique.
AB  - BACKGROUND: The lack of well standardized or characterized extracts that contain
      the relevant allergens of the appropriate fungus is resulting in a high
      heterogeneity of the commercial preparation. MATERIAL AND METHODS: Immunochemical
      detection of the allergens composition of spore and mycelium of C.
      cladosporioides was studied by electroblotting using sera from Cladosporium
      allergic patients and 125 I- anti- human IgE. A MW range of allergens between 16
      to 88 KDa was identified. The most important with a MW of 16, 20,30, 39, 43, 50,
      60 and 88 KDa. RESULTS: The allergenic composition of spore and mycelium looked
      very similar. However, partial or total inhibition of the serum with a conidial
      or mycelial extract demonstrated that the total concentration of allergens
      (particulary 20 and 60 KDa molecules) was higher in the conidium than in the
      mycelium. CONCLUSIONS: These results indicated that conidium and mycelium
      contained the same allergenic determinants but at different concentration in the
      two propagule. Results with 50 % inhibited sera demonstrated also that the total
      concentration of allergens was higher in the conidium than in the mycelium.

PMID- 16606549
TI  - Hypersensitivity reactions to metronidazole.
AB  - BACKGROUND: Hypersensitivity reactions to metronidazole are infrequently
      described. However, we believe that such reactions are increasing due to growing
      use of the drug for the treatment of amebiasis and anaerobe infections combined
      with other antibiotics. The present study assesses the need for oral provocation
      in patients with probable hypersensitivity reactions to metronidazole. METHODS:
      We performed cutaneous prick tests with spiramycin and metronidazole as well as
      epicutaneous tests with metronidazole at different concentrations in four
      patients with cutaneous reactions to Rhodogil (metronidazole plus spiramicyn).
      Controlled oral challenges were then carried out with placebo using erythromycin,
      spiramycin and metronidazole except in the last patient due to a positive prick
      test. RESULTS: Only one patient showed a positive metronidazole prick test. The
      epicutaneous tests were negative. All patients tolerated erythromycin and
      spiramycin up to therapeutic doses. Oral provocation with metronidazole proved
      positive, the first patient presenting a delayed exanthema and the other two
      early erythema and itching. CONCLUSIONS: We present four cases of cutaneous
      exanthemas caused by metronidazole (two early and two delayed) and probably
      mediated by an immune mechanism which we have only been able to demonstrate in
      one case. Taking into account the low sensitivity of the cutaneous tests (prick
      tests and epicutaneous tests), oral provocation must be considered the "gold
      standard" for establishing the diagnosis in many cases of hypersensitivity
      reactions to metronidazole.

PMID- 16606550
TI  - Home gardening may be a risk factor for contact dermatitis to Alstroemeria.
AB  - BACKGROUND: Occupational allergy among florists and people who work in cut flower
      production of Alstroemeria cultivars (Peruvian lily or Inca lily) has been
      previously reported. The allergen involved in sensitization is tulipalin A (alpha
      methylene-gamma-butyrolactone). CASE REPORT: We describe the case of a 65-year
      old woman who developed severe dermatitis on her right thumb, index and middle
      fingers and less severe dermatitis on her left palm and front of forearm with
      occasional itching of the neck and face after taking up home gardening
      activities, including cutting flowers such as Alstroemeria. METHODS: The patient
      and three healthy individuals were submitted to epicutaneous tests with the
      European standard series, the plant series, and stem portions of three suspected
      ornamental plants (Alstroemeria, Lilium and Zantedeschia), garlic, and onion.
      RESULTS: Patch tests performed in our patient, revealed an extreme reaction (+ +
      +) to Alstroemeria and alpha-methylene-gamma-butyrolactone, a strong reaction (+
      +) to propolis and wood tar mix, a weak reaction (+) to balsam of Peru, an
      irritant reaction to garlic and negative results to diallyl disulfide and the
      other components investigated. Patch tests performed in the healthy individuals
      revealed negative. CONCLUSIONS: We stress the importance of Alstroemeria as a
      cause of allergic contact dermatitis not only in workers involved in the flower
      trade, but also in other people that come into contact with this plant in their
      leisure activities.

PMID- 16606551
TI  - Erythema multiforme to amoxicillin with concurrent infection by Epstein-Barr
      virus.
AB  - BACKGROUND: The incidence of rashes following the intake of aminopenicillins
      during an acute episode of infectious mononucleosis is high, but severe cutaneous
      reactions as erythema multiforme or Stevens-Johnson syndrome are rare
      manifestations in childhood. MATERIAL AND METHODS: We report the case of a 7 year
      old girl that developed a generalized purpuric rash with target shaped areas, 9
      days after starting treatment with amoxicillin-clavulanic acid. Laboratory
      investigation revealed a significant increase of Epstein Barr virus (EBV)
      specific IgM antibody. After skin biopse she was diagnosed as erythema multiforme
      syndrome. Prick, intradermal and patch tests were performed with
      penicilloylpolylysine, minor determinant mixture, benzylpenicillin, ampicillin,
      amoxicillin, cefazoline and cefotaxime, the 24 hours reading was positive for
      aminopenicillins. Patch tests were also positive only for aminopenicillins, other
      betalactams were negative. CONCLUSIONS: The interaction between an infectious
      agent (EBV) and amoxicillin could precipitate the severe skin reaction. Patch
      test and delayed intradermal reading with amoxicilllin were an useful tool for
      the diagnosis of the etiological agent in this reaction. The negative response to
      other beta-lactams, suggests that the aminobenzyl group of the side chain of
      amoxicillin plays a predominant role in this reaction.

PMID- 16606552
TI  - Eosinophilic esophagitis.
AB  - BACKGROUND: Esophagitis is an increasingly diagnosed disease. Patients with
      gastroesophagic reflux, dysphagia, vomiting or abdominal pain, with a torpid
      response to the treatment, could be suffering from it. MATERIAL AND METHODS: A 37
      year-old male patient with background of gastroesophagic reflux and dysphagia for
      solids since 2002, self-limited diarrhea episodes and intolerance to alcoholic
      drinks due to epigastric pain. Skin prick tests, specific IgE, histamine release
      test and basophil activation test were carried out. RESULTS: Skin prick test to
      the usual allergens with negative result; prick-prick tests to egg white and
      yolk, milk and apple with positive result to egg white; total serum IgE within
      normal levels, specific IgE to egg white with positive result; histamine release
      test (HRT) and basophil activation test (BAT) with positive result to egg white
      and yolk. CONCLUSION: The patient was diagnosed eosinophilic esophagitis. The
      commercial food extracts have a great variability in their allergenic
      composition, which could result in false negative results in the prick test.
      Prick-prick with the natural food is a more sensitive technique than prick in the
      diagnosis of food allergy. There are other useful in vitro techniques, apart from
      specific IgE, in the diagnosis of food allergy. In our case, an exclusion diet of
      the involved food was more effective than other treatments for remission of the
      symptoms.

PMID- 16606554
TI  - [Efficacy of control measures to prevent MRSA transmission in health
      institutions. An up-dated view].

PMID- 16606555
TI  - [Control of methicillin-resistant Staphylococcus aureus in Spanish hospitals. A
      survey from the MRSA 2003 GEIH/GEMARA/REIPI project].
AB  - INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the
      main nosocomial pathogens. The incidence of MRSA infections is increasing in
      Spain. The objective of this study was to investigate the measures used for
      surveillance and control of MRSA in a sample of Spanish hospitals. METHODS: A
      questionnaire survey was done, including data on the incidence of MRSA
      infection/colonization for 2002, the microbiological methods used to study S.
      aureus susceptibility, and the use of control measures based on published
      guidelines. RESULTS: Sixty-one hospitals with a catchment population of 16
      million inhabitants participated. Automatic methods were most frequently used for
      routine susceptibility testing. The median incidence was 0.45 cases/100
      admissions; this data could be obtained from only 70% of the centers. In 59%, the
      incidence was indicative of high transmission. Isolation precautions were
      indicated for all patients with MRSA in 95% of the hospitals; screening of
      carriers among patients was performed in 18% to 72%, depending on the
      circumstances. Health care workers from at least one unit had been screened in
      52% of the hospitals during 2002. Mupirocin was used for the treatment of 90% of
      colonized persons. CONCLUSION: There is considerable variation in the application
      of control measures in the hospitals surveyed. National guidelines with
      recommendations for MRSA control are needed in Spain.

PMID- 16606556
TI  - [Prosthetic joint infection: a prospective study in five Catalonian hospitals].
AB  - BACKGROUND: Prosthetic joint infections are a cause of increasing morbidity and
      medical expenditure. OBJECTIVES: To determine the incidence and the clinical and
      the epidemiological characteristics of knee and hip prosthetic infections (PI) in
      patients undergoing elective surgery in five Catalonian hospitals. To determine
      the predictive factors of PI. METHODS: A total of 425 patients operated on
      between 8 January and 8 July 2001 were prospectively followed for a period of two
      years. The cumulative incidence, incidence rate and effect measures were
      determined. Logistic regression was used to identify variables associated with
      PI. RESULTS: Average age was 71 years and 63.1% were women. Antibiotic
      prophylaxis with cefazolin was given to 44.7% of the patients, with a mean
      duration of two days. Prophylaxis was administered during anesthesia induction in
      75.6% of the patients. Among the total, 63.4% of the patients were ASA 2.
      Microbiological confirmation was obtained in all the infected patients;
      Staphylococcus epidermidis was found in 58%. Fourteen PI were diagnosed, 71%
      during the first 3 months, with a cumulative incidence of 3.29% and a 3-month
      incidence rate of 63 patients/10,000 patients/month. Diabetes mellitus was the
      only variable related to PI in the multivariate analysis: 3.18, 95% CI (1.1-9.9).
      CONCLUSIONS: The cumulative incidence of PI was slightly higher than that seen in
      other studies. Variations were observed in the antibiotic used for prophylaxis,
      and the place where it was administered. PI occurred 3.18 times more frequently
      in diabetic patients.

PMID- 16606557
TI  - [Cytomegalovirus detection in blood and bronchoalveolar lavage, and prophylaxis
      or preemptive treatment with ganciclovir in children with allogeneic stem cell
      transplantation].
AB  - INTRODUCTION: Cytomegalovirus disease is one of the complications of allogeneic
      stem cell transplantation (SCT). The objective of this study was to determine the
      frequency of CMV infection and CMV disease in children undergoing allogeneic SCT,
      and in whom antigenemia and bronchoalveolar lavage (BAL) were performed for early
      detection of CMV infection. METHODS: A total of 59 consecutive children who
      underwent allogeneic-identical, related SCT were prospectively evaluated. The
      patients were classified into: group 1 (low risk), donor and recipient CMV
      seronegative; group 2 (intermediate risk), donor and/or recipient CMV
      seropositive; and group 3 (high risk), recipient with acute graft-versus-host
      disease (GVHD) resistant to steroid therapy. Weekly antigenemia was carried out
      in all the patients until day 1100. In antigenemia-negative patients in group 2,
      BAL was performed on day 145. Patients in groups 1 and 2 with positive
      antigenemia or BAL received ganciclovir until day 1100. In group-3 children,
      ganciclovir was given until GVHD was controlled. RESULTS: The frequency of CMV
      infection and CMV disease was 45% and 1.5%, respectively. Testing for CMV in BAL
      in group-2 patients increased the frequency of early diagnosis by 10%.
      Ganciclovir was administered to 57% of the patients in this study. CONCLUSION: As
      compared to other series, a lower frequency of CMV disease and a reduction in
      ganciclovir use were observed with this strategy.

PMID- 16606558
TI  - [Laboratory Network within the Polio Eradication Initiative (1998-2003): six
      years of surveillance for acute flaccid paralysis in Spain].
AB  - INTRODUCTION: Worldwide poliomyelitis eradication was proposed in 1988 by the
      World Health Organization (WHO), based on reaching and maintaining high
      vaccination coverage and on implementing effective poliovirus infection
      surveillance systems. METHODS: In Spain the surveillance system focuses on active
      searching for acute flaccid paralysis cases through a nine-laboratory network,
      coordinated by the National Poliovirus Laboratory (NPL) in the National Center of
      Microbiology, and supported by Autonomous Community epidemiologists.
      Additionally, the Network sends enterovirus isolation data from other syndromes.
      The Laboratory Network is responsible for the primary virological study, while
      the NPL characterizes all polioviruses and the most epidemiologically relevant
      non-polio enteroviruses. RESULTS: A total of 54,533 samples were studied during
      the six-year period, and enteroviruses were detected in 9%. All the polioviruses
      isolated (n = 196), were characterized as Sabin-like (poliovirus vaccine), and
      among the non-polio enteroviruses, the most frequent was Echovirus 30. A total of
      3% of the samples studied corresponded to the 268 acute flaccid paralysis cases
      or their contacts. DISCUSSION: According to the results and the WHO virological
      classification, Spain can be considered polio-free. However, the geographic
      situation of our country may facilitate the introduction of wild polioviruses
      that can give rise to imported poliomyelitis. Hence, the laboratory network
      should actively continue to participate in all the proposed WHO strategies,
      particularly maintenance of the poliomyelitis eradication infrastructures, and
      continuing monitoring and vaccination.

PMID- 16606559
TI  - [Pyomyositis: retrospective review in a third-level hospital in the north of
      Spain].
AB  - OBJECTIVE: To describe the clinical, radiological and microbiological features of
      a series of patients diagnosed with pyomyositis in a tertiary care university
      affiliated center over a 12-year period. PATIENTS AND METHODS: The medical
      records of all patients diagnosed with pyomyositis between January 1992 and
      December 2003 were reviewed. The charts were retrieved from the hospital
      database. Data were extracted according to a standardized protocol and included
      clinical, radiological, laboratory and microbiological parameters. RESULTS: A
      total of 54 patients (mean age, 50 years, 61% men) had pyomyositis. The most
      frequent predisposing factors were diabetes mellitus (22%) and traumatic injury
      (20%), followed by neoplasms (9%). Primary pyomyositis was diagnosed in 25
      patients (55%), and a contiguous source of infection was detected in the
      remainder, with skin infection being the most frequent (40%). The most common
      presentation was isolated inflammatory signs with or without other symptoms
      (94%). Isolated fever was documented in only one patient. Ultrasonography was the
      most common diagnostic procedure performed (32%), followed by CT scanning (18%).
      Forty-five patients underwent a drainage procedure combined with antibiotic
      therapy. Pyomyositis was monomicrobial in 20 cases, and polymicrobial in 12. The
      most frequent pathogen was Staphylococcus aureus followed by coagulase-negative
      staphylococci (6 cases). Sepsis developed in 4 patients, and recurrence was
      observed in 8 (15%). Mortality was 10% (5 patients). CONCLUSIONS: Pyomyositis is
      a relatively uncommon infection in temperate climates, and is often considered
      late in the diagnostic workup. Physicians should bear this disease in mind to
      avoid diagnostic delays and initiate prompt therapy, in order to improve the
      prognosis of these patients.

PMID- 16606560
TI  - [Staphylococcus aureus infections: new challenges from an old pathogen].
AB  - Staphylococcus aureus is a versatile organism with several virulent
      characteristics and resistance mechanisms at its disposal. It is also a
      significant cause of a wide range of infectious diseases in humans. S. aureus
      often causes life-threatening deep seated infections like bacteremia,
      endocarditis and pneumonia. While traditionally confined mostly to the hospital
      setting, methicillin-resistant S. aureus (MRSA) is now rapidly becoming rampant
      in the community. Community-acquired MRSA is particularly significant because of
      its potential for unchecked spread within households and its propensity for
      causing serious skin and pulmonary infections. Because of the unfavorable outcome
      of many MRSA infections with the standard glycopeptide therapy, new antimicrobial
      agents belonging to various classes have been introduced and have been evaluated
      in clinical trials for their efficacy in treating resistant staphylococcal
      infections. A number of preventive strategies have also been suggested to contain
      the spread of such infections. In this review, we address the recent changes in
      the epidemiology of S. aureus and their impact on the clinical manifestations and
      management of serious infections. We also discuss new treatment modalities for
      MRSA infections and emphasize the importance of preventive approaches.

PMID- 16606561
TI  - [Microbiological diagnosis of viral hepatitis].
AB  - Hepatitis of viral aetiology caused by hepatotropic virus (A, E, B, D and C)
      represents an important work load for the clinical virology laboratory. Most of
      the diagnostic is based upon detection in serum and plasma samples of different
      serological and virological markers, which correlates with different infection
      stages. In chronic infection by HBV and HCV is necessary to perform diagnostic by
      molecular methods as well as antigen detection in sequential samples along the
      course of the disease taking into account that a reliable storage must be
      provided for stability of structural components of the virus. Recent knowledge
      about mutations variants in some of the virus may alter the validity of
      particular markers.

PMID- 16606562
TI  - [Subcutaneous lesion in a renal transplant recipient].

PMID- 16606563
TI  - [Parasitosis in an Ecuadorian girl].

PMID- 16606564
TI  - [A 56-year-old woman with pain and crepitations in the left lower limb].

PMID- 16606565
TI  - [Cryptococcal meningitis in HIV-negative patients].

PMID- 16606566
TI  - [Comparison of growth and loss of viability of Streptococcus pneumoniae in FAN
      aerobic or BACTEC Plus aerobic culture bottles].

PMID- 16606567
TI  - [Thyroid alterations following treatment with pegylated interferon and ribavirin:
      differences between HIV-coinfected and non-coinfected patients].

PMID- 16606568
TI  - [Medical errors in pediatrics and neonatology. A new multidisciplinary approach
      is required].

PMID- 16606569
TI  - [Medication prescription and transcription errors in a neonatal unit].
AB  - BACKGROUND: Medication errors occur because of pitfalls in one or more of the
      steps involved in the process of drug administration and should be considered as
      system errors. They should never be considered as human errors with assignment of
      responsibility. Rather, their causes should be analyzed to prevent repetition.
      The ultimate aim should be to improve working procedures to avoid these errors.
      PATIENTS AND METHODS: A total of 122 prescriptions were prospectively analyzed,
      along with their corresponding transcription to the nursing notes. Their
      legibility, dose, units, route of administration, and administration interval
      were evaluated. Units per kilogram of body weight and the use of generic names
      were also recorded. RESULTS: Prescription errors were detected in 35.2 % of the
      prescriptions reviewed. The most frequent errors were related to dosing (16.4 %).
      Analysis of the quality of the prescriptions revealed that 61.5 % of the drugs
      were prescribed by their generic name, but only 4.1 % specified the dose per
      kilogram of body weight. Errors were detected in 21.3 % of transcriptions, the
      most frequent being the absence of the administration route (7.4 %). The generic
      name was used in 57.4 % of the transcriptions. CONCLUSIONS: In the busy and
      complex environment of neonatal units, medication errors can be frequent.
      However, most of these errors are trivial and do not harm patients. Medication
      errors are indicators of the quality of the healthcare provided. Therefore, their
      detection and systematic analysis of their causes can contribute to their
      systematic prevention, thus improving the healthcare delivery process.

PMID- 16606570
TI  - [Diode laser therapy in retinopathy of prematurity: more than a decade of
      experience].
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is one of the most important causes
      of blindness in childhood. The introduction of diode laser has represented a
      significant advance in its treatment. The aim of the present study was to
      evaluate our results in the treatment of this entity after more than a decade of
      experience. PATIENTS AND METHODS: One hundred eighty-two eyes in 92 premature
      infants with ROP treated with diode laser in the Hospital Universitario Miguel
      Servet from 1992 to 2003 were studied. The characteristics of the population
      (gestational age, birth weight, sex, stage and affected zone) and treatment
      outcomes were analyzed. The change in the criteria indicating this treatment was
      also analyzed. RESULTS: In the treated population, mean gestational age (27.9
      weeks) and birth weight (1015.9 g) were similar to those in other published
      studies. A favorable outcome was achieved in 169 of the 182 cases (92.8 %). The
      change in criteria increased the proportion of favorable outcomes to 96.1 %.
      DISCUSSION: Diode laser therapy is currently the treatment of choice in ROP. This
      treatment, based on guidelines for earlier intervention, provide greater efficacy
      without increasing morbidity.

PMID- 16606571
TI  - [Procalcitonin for the diagnosis of neonatal sepsis of vertical transmission].
AB  - OBJECTIVE: To evaluate procalcitonin (PCT) as a diagnostic marker of neonatal
      sepsis of vertical transmission and to compare the results of PCT with those of
      the most widely used laboratory tests for sepsis. PATIENTS AND METHODS: A
      prospective study was conducted in 136 blood samples from 69 newborn infants
      admitted to a neonatal department. PCT, C-reactive protein (CRP), leukocyte
      count, and the immature-to-total neutrophil ratio (I/T ratio) were measured. The
      PCT reference range of controls from 0 to 72 hours of life was constructed, and
      the diagnostic efficiency of the tests was calculated, with their 95 % confidence
      intervals (95 % CI). RESULTS: This study included 35 controls, 24 neonates with
      noninfectious disorders, and 10 neonates with sepsis (5 with culture-proven
      sepsis). PCT, CRP, and the I/T ratio discriminated septic from nonseptic
      patients. Their areas under the ROC curve were 0.696 (p = 0.009), 0.735 (p =
      0.002), and 0.703 (p = 0.006), respectively, with no statistically significant
      differences. The accuracy of PCT, CRP, and leukocyte count improved after 24
      hours of life with areas under the ROC curve of 0.813 (p = 0.007), 0.826 (p =
      0.005), and 0.841 (p = 0.003), respectively. Overall, PCT detected vertically
      transmitted sepsis with a sensitivity of 68.4 % (95 % CI: 46.0 %-84.6 %),
      specificity of 82.4 % (95 % CI: 72.2 %-89.4 %), positive likelihood ratio of 3.89
      (95 % CI: 2.18 %-6.96 %), and negative likelihood ratio of 0.38 (95 % CI: 0.19 %
      0.76 %), similar to those of CRP. CONCLUSIONS: PCT may be a useful marker for the
      diagnosis of vertically transmitted sepsis. Studies with larger sample sizes are
      required to establish the accuracy of PCT.

PMID- 16606572
TI  - [Procalcitonin for the diagnosis of nosocomial neonatal sepsis].
AB  - BACKGROUND: Nosocomial sepsis is a major problem in neonatal units. Because the
      clinical signs are nonspecific, highly reliable diagnostic markers are required
      to guide diagnosis. The aim of this study was to evaluate the utility of
      procalcitonin (PCT) as a diagnostic marker for nosocomial neonatal sepsis, and to
      compare the results of PCT with those of the most widely used laboratory tests
      for sepsis. PATIENTS AND METHODS: Twenty neonates with nosocomial sepsis and 20
      controls aged 4-30 days were included in a prospective study performed in a
      neonatal intensive care unit. PCT, C-reactive protein (CRP), leukocyte count, and
      the immature-to-total neutrophil ratio (I/T ratio) were measured at onset of
      signs of infection. The sensitivity, specificity, and likelihood ratio for a
      positive (LR+) and a negative (LR-) result were calculated. RESULTS: PCT, CRP,
      and the I/T ratio discriminated septic from nonseptic patients. Their areas under
      the ROC curve were 0.849, 0.880, and 0.884, respectively, with no statistically
      significant differences. Optimal cut-off values were: PCT > or = 0.65 ng/ml
      (sensitivity 85 %, specificity 80 %, LR 1 4.25, LR- 0.19), PCR > or = 5 .g/ml
      (sensitivity 80 %, specificity 95 %, LR 1 16, LR- 0.21), and I/T > or = 0.03
      (sensitivity 90 %, specificity 75 %, LR 1 3.6, LR- 0.13). CONCLUSIONS: PCT may be
      a useful marker for the diagnosis of nosocomial neonatal sepsis. Studies with
      larger samples are required to compare the accuracy of PCT with that of other
      markers of sepsis.

PMID- 16606573
TI  - [Middle latency auditory evoked potentials in critical care children: preliminary
      study].
AB  - BACKGROUND: Middle latency auditory evoked potentials (MLAEP) reflect changes in
      electroencephalogram waves after an auditory signal and represent the earliest
      cortical response to acoustic stimulus. They are therefore used to measure
      variations in the level of consciousness. MLEAP have been used to measure the
      depth of anesthesia during surgical procedures, but experience in critical care
      patients is very limited. OBJECTIVE: To analyze the utility of MLAEP for
      monitoring the level of sedation in critically ill children. METHODS: Level of
      consciousness was monitored through MLAEP by placing special headphones and three
      sensors situated in the frontal and preauricular regions. Simultaneously, the
      level of sedation was measured using the COMFORT scale and the Bispectral Index
      (BIS) in distinct clinical situations. RESULTS: We studied six critically ill
      children in whom MLAEP helped us to evaluate the level of consciousness: light
      sedation, natural sleep, deep sedation, sedation in a paralyzed child, and brain
      death. MLAEP showed a good correlation with the COMFORT scale and BIS in light
      and deep sedation and were effective in the early detection of brain death in one
      patient. In the paralyzed patient, MLAEP was able to detect undersedation. In one
      patient, a pacemaker interfered with the MLAEP signal. CONCLUSIONS: MLAEP can be
      useful in evaluating the level of consciousness and sedation in critically ill
      children. Further studies with larger samples are required to analyze the
      limitations and reproducibility of this type of monitoring in children of
      different ages.

PMID- 16606574
TI  - [Idiopathic short stature: definition and treatment].
AB  - Short stature is the leading cause of consultation in Pediatric Endocrinology.
      Decreased growth velocity and abnormally short height are characteristic of
      several different nosologic entities. Some are well characterized, while others
      correspond to what is known as idiopathic short stature (ISS). ISS includes
      children who grow less than 2 SD of the mean height values corresponding to their
      peers of similar age and the same sex, in whom the known causes of short stature
      have been ruled out. The diagnosis of ISS does not include children who only
      present a constitutional delay in growth and development. Several clinical trials
      have demonstrated the efficacy of growth hormone (rhGH) treatment in achieving
      catch-up growth in these children. Therefore, ISS should be kept in mind in the
      diagnosis of patients with short stature and abnormal growth patterns, who may
      benefit from rhGH treatment.

PMID- 16606575
TI  - [Consensus on the treatment of asthma in pediatrics].

PMID- 16606577
TI  - [D-lactic acidosis in an 11-year-old patient with short bowel syndrome].
AB  - The short bowel syndrome is the result of a congenital or acquired loss of a
      large part of the small intestine. The most frequent causes of surgical resection
      of the intestine in infants are arterial or venous thrombosis, intestinal
      volvulus, necrotizing enterocolitis, and Crohn's disease. Symptoms include
      nutrient and electrolyte malabsorption, steatorrhea and diarrhea, which can
      result in failure to thrive. The consequences of extensive small bowel resections
      consist of nutritional deficiencies, gastric acid hypersecretion,
      nephrolithiasis, cholelithiasis and lactic acidosis. Of these, D-lactic acidosis
      is an infrequent but important complication because of the symptoms that it can
      produce. D-lactic acid in the human organism is generated by intestinal bacteria,
      D-lactate ingestion, or endogenous production in the methyl glycoxylase pathway.
      Neurological symptoms such as somnolence, ataxia or altered behavior in a patient
      with short bowel syndrome should make us think of D-lactic acidosis caused by
      bacterial overgrowth. We present the case of an 11-year-old boy with short bowel
      syndrome secondary to multiple resections during the postnatal period who was
      admitted to hospital for episodes of confusion and altered behavior. The
      diagnosis was lactic acidosis. Outcome was favorable due to prompt instauration
      of treatment.

PMID- 16606576
TI  - [Arterial stroke after birth trauma].
AB  - Perinatal arterial stroke is a significant cause of neurological deficit,
      including mental retardation, delayed motor development, epilepsy, and severe
      cognitive impairment. Most strokes occur in term neonates, due to thromboembolism
      from an intracranial or extracranial vessel associated with a risk factor such as
      asphyxia at birth and heart, hematological or infectious diseases. An association
      with instrumental delivery has not been clearly demonstrated, although several
      cases have been described in the literature. The incidence of stroke in the
      perinatal period is estimated to be 1/4000 term neonates per year. We describe
      three new cases of stroke in term neonates with instrumental delivery and
      describe the etiopathogenesis, diagnosis and outcome of this entity.

PMID- 16606578
TI  - [Progressive primary tuberculosis with endobronchial involvement. Benefits of
      multislice helical computed tomography].
AB  - OBJECTIVES: To assess computed tomography (CT) imaging findings in progressive
      primary tuberculosis and to determine the use of the multislice images obtained.
      PATIENTS AND METHODS: We report the case of a 37-day-old infant admitted to
      hospital because of persistent fever despite antimicrobial therapy. Thoracic X
      ray and multislice helical CT (CT Light speed i1.6 GE) were performed with 3
      dimensional and virtual endoscopy reconstructions. RESULTS: CT showed mediastinal
      and hilar necrotic lymph nodes, pulmonary parenchymal involvement with miliary
      pattern, and multiple cavitated consolidations. Endobronchial involvement was
      clearly visualized by virtual endoscopy and was confirmed by fiberoptic
      bronchoscopy. CONCLUSIONS: Virtual endoscopy is a new, less invasive alternative
      radiological technique to fiberoptic bronchoscopy that may influence the
      management of patients with tuberculosis with endobronchial involvement.

PMID- 16606579
TI  - [Shock and digestive symptoms in a neonate: a severe presentation of allergy to
      cow's milk proteins].

PMID- 16606580
TI  - [Hypochondroplasia due to the N540K mutation].

PMID- 16606581
TI  - [Drug administration in newborns. Is clinical experience enough?].

PMID- 16606582
TI  - [Hypertrophic lichen planus in childhood].

PMID- 16606583
TI  - [Lichen sclerosus with genital and extragenital lesions].

PMID- 16606584
TI  - [Abdominal mass and eosinophilia in an Ethiopian boy].

PMID- 16606585
TI  - Epidemiology of skin diseases in Europe.

PMID- 16606586
TI  - The skin and its diseases: an overview.

PMID- 16606587
TI  - [Bioinformatic analysis of adenoma-normal mucosa SSH library of colon].
AB  - We established a colonic adenoma-normal mucosa suppressive subtraction
      hybridization (SSH) library in 1999. In this study, we wanted to explore the
      expression profile of all candidate genes in this library. We developed an EST
      pipeline which contained two in-house software packages, nucleic acid analytical
      software and GetUni. The nucleic acid analytical software, an integrator of the
      universal bioinformatics tools including phred, phd2fasta, cross_match,
      repeatmasker and blast2.0, can blast sequences of differential clones with the
      downloaded non-redundant nucleotide (NR) database. GetUni can cluster these NR
      sequences into Unigene via matching with the downloaded Homo Sapiens UniGene
      database. Sixty-two candidate genes in A-N library were obtained via the high
      throughput automatic gene expression bioinformatics pipeline. Gene Ontology
      online analysis revealed that ribosome genes and immunity-regulating genes were
      the two most common categories in the KEGG or Biocarta Pathway. We also detected
      the expression of 2 genes with highest hits, Reg4 and FAM46A, by semi
      quantitative RT-PCR. Both genes were up-regulated in 10 or 9 out of 10 adenomas
      in comparison with the paired normal mucosa, respectively. The candidate genes in
      A-N library would be of great significance in disclosing the molecular mechanism
      underlying in colonic adenoma initiation and progression.

PMID- 16606588
TI  - [Meta-analysis of the association of the LRP C766T polymorphism with the risk of
      Alzheimer's disease].
AB  - A C-to-T polymorphism in exon 3 of the low density lipoprotein receptor-related
      protein 1 (LPR-1) gene has been implicated as a risk factor for Alzheimer's
      disease (AD). The authors performed a meta-analysis to investigate the
      association between the C766T polymorphism in the LPR-1 gene and the risk for AD.
      Nineteen references were retrieved through Medline, Cochran Library and CBM
      search from 1997 to 2004. Similar search strategies were applied to each of these
      databases. Studies which were eligible for the meta-analysis should meet the
      following inclusion criteria: presentation of original data and a cross-sectional
      design, AD as the outcome of interest, an odds ratio (or enough information to
      calculate it) reported to quantify the association between the frequencies of
      genotypes and/or alleles of LPR-1 gene C766T polymorphism and the risk for AD.
      All analyses were performed with Review Manager 4.2. A total of 3,560 AD patients
      and 3,476 control subjects were analyzed according to the random effect model
      because some between-study heterogeneity was found (P<0.01). The combined data
      statistics revealed that there was no statistical difference (test for overall
      effect: Z=1.74, P=0.08, OR=1.17, 95% CI: 0.98-1.39; Z=1.31, P=0.19, OR=1.11, 95%
      CI: 0.95-1.31) in the frequencies of allele and genotype between the AD patients
      and the controls. The meta-analysis showed that the LPR-1 polymorphism was not a
      major risk factor for AD, although a small effect of the polymorphism for AD risk
      could not be excluded.

PMID- 16606589
TI  - [Gene frequency of 5 genetic characters in 6 nationalities in southern Guizhou].
AB  - The gene frequency of 5 characters was reported in Buyi, Miao, Shui, Maonan,
      Dong, and Han nationalities in southern Guizhou, and analyzed for statistical
      significance among these nationalities. The results showed that: (1) For Hair
      forms and Nasal profile, the frequency of the dominant gene was lower than that
      of theirs recessive gene, but the opposite was true for Nostril forms. (2) Among
      different nationalities, the difference of gene frequency of Mongoloid fold,
      Nasal profile, Hair forms and Eye fold of the upper eyelid was quite significant,
      which was followed by that of Nostril forms.

PMID- 16606590
TI  - [An association study between paranoid schizophrenia and four genes involved in
      dopamine metabolism].
AB  - Schizophrenia is a complex disease caused by interactions among multiple genes.
      Reports of one of its susceptibility genes, ethyltracatechol-O-mnsferase (COMT)
      have been conflicting. In the present study on paranoid schizophrenia, we have
      performed a multilocus association study to analyze the interactions among 4
      genes that are involved in dopamine metabolism. Result supports the hypothesis
      that COMT-136-BclI regulates Val108/158Met. When the genotype of the former is
      CC, Met (A) is the genotype of susceptibility allele Val108/158Met; and when the
      genotype of the former is GG, Val (G) is the genotype of susceptibility allele
      Val108/158Met. This new hypothesis may explain the conflicting results about
      Val108/158Met (COMT) obtained by single-locus analyses. It also illustrates that
      multilocus analysis is necessary for the research of complex diseases.

PMID- 16606591
TI  - [Genetic diversity of seven miniature pig breeds (strains) analyzed by using
      microsatellite markers].
AB  - Twenty-seven microsatellite markers recommended by the Food and Agriculture
      Organization (FAO) and the International Society for Animal Genetics (ISAG) were
      used to analyze the genetic diversities of 7 Chinese native miniature pig
      breeds/strains (Jiuyang Xiang Pig, Jianbai Xiang Pig, Congjiang Xiang Pig,
      Huanjiang Xiang Pig, Black Xiang Pig, Wuzhishan Pig, and Diannan Small Ear Pig)
      and 3 western pig breeds (Duroc, Large White, and Landrace). The results indicate
      that there exists, in general, a high degree of genetic variability within the 7
      miniature pig breeds. However, the genetic variability in Jiuyang Xiang Pig,
      Jianbai Xiang Pig, Huanjiang Xiang Pig, and Congjiang Xiang Pig (average PICs
      being 0.61-0.64) was significantly lower than that in the other three miniature
      pig breeds (average PICs being 0.60-0.84). The genetic divergence among Jiuyang,
      Jianbai, Huanjiang, and Congjiang was very small (Nei's standard genetic
      distances being 0.12-0.22), but it was large between them and the other three
      miniature pig breeds (Nei's standard genetic distances being 1.61-1.96), and even
      larger between them and the three foreign breeds (Nei's standard genetic
      distances being 1.99-3.30). Cluster analysis reveals three obvious clusters for
      the 10 breeds: Jiuyang, Jianbai, Huanjiang, and Congjiang are in one cluster, the
      other three miniature pig breeds in the other, and the three foreign breeds in
      the third. These results are consistent with the geography distribution and
      origin of these breeds.

PMID- 16606592
TI  - [Analysis of SNPs in exons 2 and 3 of the leptin gene in wild boar, swine and
      hybrid swine].
AB  - Leptin is a 167-amino acid hormone mainly expressed in the fat tissue. It serves
      as an important regulator of energy uptake and consumption through action on the
      hypothalamus. Herein single nucleotide polymorphisms (SNPs) were detected in
      exons 2 and 3 of the Leptin gene in wild boar, swine and half-bred swine by PCR
      SSCP. Cloning and sequencing of homozygous fragments revealed the following
      variations in the coding region: a silent T to C transversion at nucleotide 214;
      CG to GC at nucleotides 364 and 365, which converts Arg to Ala; a silent G to A
      transversion at nucleotide 426; a T insertion at nucleotide 451 resulting in
      frameshift; and a G to T transversion at nucleotide 462.

PMID- 16606593
TI  - [Linkage analysis of five genes in pigs using radiation hybrid clone panel].
AB  - RH (radiation hybrid) has proved to be an effective method in constructing human
      genome maps (including ESTs, STSs and microsatellites). In this study, based on
      the information of five human genes (FMR1, IDS, FATE, BGN, F8A) on the X
      chromosome, the linkage relationship of these five genes in pigs were analyzed by
      a panel of 96 radiation hybrid cell lines. The results showed that FMR1, IDS,
      FATE, BGN, F8A were in the same linkage group, when LOD was set at 4. When LOD
      was set at 5, FMR1 and IDS were in the one group, FATE and BGN in the other
      group, and F8A was in a group by itself.

PMID- 16606594
TI  - [Analysis of mitochondrial 12S rRNA gene polymorphism in cattle].
AB  - The mitochondrial DNA 12S rRNA in seven Chinese local yellow cattle breeds, one
      cultivated breed and three imported breeds was studied by single-strand
      conformation polymorphism (SSCP). Three haplotypes (I, II , III) were detected,
      with haplotype I found only in one cattle of the Jinnan breed. Haplotype II did
      not appear in the foreign cattle breeds and low in Chinese-Simmental breed but
      was rich in Chinese local breeds. Haplotype III had the widest distribution and
      was present in ten cattle breeds. The average polymorphism information content
      (PIC) for Chinese cattle between 0.232-0.423 was modest, which suggested relative
      abundance of genetic resources for the Chinese native cattle.

PMID- 16606595
TI  - [Biological characteristics of the 5' regulatory region of FSHR gene in sheep].
AB  - The 5' transcriptional promoter regulation region of FSHR gene was cloned and
      analyzed in Little-tailed Han sheep, Tan sheep and Australian Merino sheep.
      Comparison of 15 transcriptional regulatory elements in the FSHR gene showed no
      difference in the regulatory region of FSHR gene among the three breeds. The
      results showed no association between sheep breeds and 5' transcriptional
      promoter regulation region and eliminated the possibility that the mutation of
      transcriptional regulation region can affect the transcription of FSHR gene in
      sheep.

PMID- 16606596
TI  - [Population genetics of Rhinopithecus bieti: a study of the mitochondrial control
      region].
AB  - Yunnan snub-nose monkey (Rhinopithecus bieti) is a famous endangered primate in
      China. So far, however, studies on its population genetics based on DNA sequences
      are not available. In this paper, the whole mitochondria control region of the
      samples from Weixi, Yunan Province as well as the whole cytochrome b gene in some
      individuals were sequenced. A deep divergence was observed within the Weixi
      population, which was confirmed after excluding the possibility of it being a
      nuclear pseudogene. Nonetheless, if the effects of population structure and
      migration are considered, the true level of polymorphism of the Weixi population
      may be not as high as observed.

PMID- 16606597
TI  - [Cloning and sequence analysis of a novel member of the rab gene family from
      Euplotes octocarinatus].
AB  - Rab proteins belong to a subfamily of small GTP-binding proteins of the Ras
      superfamily, which play an important role in intracellular vesicular traffic. In
      this study, a rab gene was obtained from Euplotes octocarinatus by polymerase
      chain reaction (PCR) and RT-PCR. The rab gene from macronucleic DNA was 884 bp in
      length, including non-coding regions and telomeric sequences at both ends. The
      rab gene from micronuclear DNA (723 bp), lacking of internal eliminated
      sequences, was identical to rab gene from macronuclear DNA. RT-PCR showed that
      the opening reading frame of the rab gene was 663 bp long. The rab gene from
      macronuclear DNA contained an intron of 60 bp at the position from 153 bp to 212
      bp of macronuclear DNA. The rab gene had two in-frame TGAs encoding for cysteine
      in Euplotes octocarinatus. The rab gene used TAG as stop codon, which was the
      first report in Euplotes octocarinatus. The result of BLAST in NCBI demonstrates
      that the Rab shares a homology of 49-52% at the amino acid level with Rab1
      proteins from a number of other eukaryote, which suggesting that the Rab is a
      Rab1 homolog. The rab gene was therefore designated Eo-rab-1N (GenBank accession
      number: DQ105562). The evolution of Eo-rab-1N was analyzed using phylogenetic
      tree of amino acids sequences of Rab1 obtained from GenBank.

PMID- 16606598
TI  - [Molecular cloning and expression analysis of a SUPERMAN-like zinc finger protein
      gene in upland cotton].
AB  - The zinc finger proteins belong to the largest family of regulatory transcription
      factors, which play an important role in growth and development in animal and
      plant systems. SUPERMAN-like zinc finger protein gene has only one "finger like"
      motif. A pair of degenerate primers was designed according to the conserved
      regions, and 3 kinds of EST of this family were isolated from cotton through RT
      PCR. The full length of one SUPERMAN-like zinc finger protein also has been
      acquired. The entire coding region is 744 bp and encodes a polypeptide of 248
      amino acids with 40% homology to RBE protein of Arabidopsis deposited in the
      GenBank. This gene was designated as GZFP. It has the conserved zinc finger
      domain and the leucine rich region at the carboxyl terminus but no intron in the
      coding region. GZFP also has the plant nuclear localization signal. GZFP shows a
      more expression pattern in floral buds, ovaries, petals and roots than in phloem,
      xylem, fibers, leaves and seeds of cotton by RT-PCR, although it has a very low
      detection level and there is not any homologous ESTs found in the GenBank.
      Analysis of the 5' flanking sequence shows there are several regulatory elements
      responsible for pollen and root expression, four core sites required for binding
      of Dof proteins and four light-regulated elements.

PMID- 16606599
TI  - [PCR-RFLP analysis on Roegneria, Elymus, Hystrix and Kengyilia in Triticeae
      (Poaceae)].
AB  - PCR-RFLP of Plasmon on 23 species of Roegneria, Elymus, Hystrix and Kengyilia and
      1 outgroup (Triticum aestivum L.) was carried out. The segments amplified with 3
      cpDNA and 3 mtDNA universal primers were digested by 15 restriction
      endonucleases. Among 329 bands produced, 304 were polymorphic (92.4%). PCR-RFLP
      results showed that polymorphisms existed between the four genera and between the
      species in Roegneria, Elymus, Hystrix and Kengyilia, and genetic similarity
      coefficient was high. Roegneria grandis, R. aristiglumis, R. elytrigioides, R.
      alashanica and R. magnicaespes were grouped, while R. caucasica, R. ciliaris, R.
      amurensis and R. japonensis clustered together. Species of Kengyilia clustered
      independently. Five species of Elymus, 3 of Hystrix and Roegneria kamoji grouped
      together. The results suggested Kengyilia was a valid genus. As more cytological
      and molecular data are available, the taxonomic status of Roegneria, Elymus and
      Hystrix will be recognized.

PMID- 16606600
TI  - [Analysis on the major gene and polygene mixed inheritance of lycopene content in
      fresh consumptive tomato fruit].
AB  - Two cultivars significantly different in lycopene content were used for the study
      of inheritance pattern of lycopene content in fresh consumptive tomato fruit.
      Combination analysis of six generations proved that a major gene plus additive
      dominance-epistasis polygenes dominate the inheritance of lycopene in fresh
      consumption tomato. The major gene heritability in B1, B2 and F2 was 6.85%,
      34.78% and 58.33%, respectively, and the polygene heritability was 58.48%, 30.69%
      and 0, correspondingly.

PMID- 16606601
TI  - [Cloning of alpha-bungarotoxin gene and its prokaryotic expression as a non
      fusion protein].
AB  - On the basis of the reported amino acid sequence of alpha-bungarotoxin (alpha
      BGT), DNA sequence of alpha-BGT was deduced and fourteen partially complementary
      oligonucleotides were designed and synthesized. A plasmid carrying the coding
      region of alpha-BGT was obtained by primer extension, PCR and ligation with pMD
      18-T. The target fragment was digested with Xba I and EcoR I, recovered and
      ligated with pET28a(+). The resultant expression vector was transformed into BL21
      (DE3), BL21 (DE3) Codon plus, and BL21 (DE3) plysS, respectively. Recombinant
      alpha-BGT was expressed in BL21 (DE3) and was analyzed by 15% Tris/tricine SDS
      PAGE. The result showed that the recombinant protein, mostly found in inclusion
      bodies, accounted for 11.98% of the total bacterial lysate. The expression
      capacity could be increased to 16.28% by optimizing expression conditions.
      Western blotting results showed that the expressed protein had similar
      immunogenicity with the natural alpha-BGT protein purified from the venom of
      Krait Bungarus spp. In vivo toxicity assay of purified and renatured proteins in
      mice showed that LD50 was about 1.28 microg/g.

PMID- 16606602
TI  - [Computational analysis of signal peptide-dependent secreted protein in
      Caenorthaditis elegans ws123].
AB  - The internet-based softwares SignalP v3.0, TargetP v1.01, big-PI predictor and
      TMHMM v2.0 were combined to predict the signal peptides and the signal peptide
      dependent secreted proteins from the 19,855 ORFs in Caenorthaditis elegans ws123
      genome. 1,990 proteins were predicted to be secreted and to contain signal
      peptides among 19,855 proteins, among which 1,936 have SignalPase I signal
      peptide (containing 41 with RR-motif signal peptide), 53 have SignalPase II
      signal peptide and one has SignalPase IV signal peptide. The signal peptides of
      742 secreted proteins include only H-domain and C-domain, but no typical N
      domain; the signal peptides of other 1,248 secreted proteins include all three
      domains. Although the amino acids constitution of the SignalPase I signal
      peptides were similar in general between Caenorthaditis elegans and prokaryote,
      there were apparently small differences, and the amino acid composition of
      Caenorthaditis elegans are more diverse and less conserved. But there are
      distinct differences on the amino acid composition of SignalPase II signal
      peptides. The signal peptides of Caenorthaditis elegans were more diverse than
      unicellular eukaryotic organism. The signal peptides of a few proteins were
      exactly the same. We used the BLAST 2 SEQUENECES aligning method to compare the
      homology among the secreted proteins with the same signal peptides. The alignment
      results indicated that the genes sharing the same signal peptide sequences were
      homologous to each other and were likely to have arisen from gene duplication.

PMID- 16606603
TI  - [Comparison of different transformation methods for Monascus sp].
AB  - In order to facilitate the producer of polyketide pathway, four different
      transformation methods were tested and compared in an attempt to develop the
      genetic transformation system of Monascus sp. Using vector pBC-Hygro, the fungus
      was transformed to be hygromycin B-resistant, by conventional transformation as
      well as electroporation based on protoplast, electroporation based on germinated
      conidia, and restriction enzyme-mediated integration (REMI). Electroporation
      based on germinated conidia was found to be inappropriate for transforming
      Monascus sp. due to a low transformation frequency. The conventional
      transformation and electroporation technique based on protoplasts were thought
      not to be fit for transforming Monascus sp., due to a low stability of
      transformants though they yielded up to 135 transformants and 125 transformants
      per microgrammol/Lol/Le DNA, respectively. Transformant number was increased by
      20-fold by REMI (2,500 transformants per microgrammol/Lol/Le DNA) and 70%-75% of
      them were stable. REMI technique would be very beneficial to the establishment of
      the genetic transformation system of Monascus sp.

PMID- 16606604
TI  - [Myopia and genetics].
AB  - The physiological manifestation of myopia is error of refraction. The incidence
      of myopia in Asian population is increasing much more rapidly compared with
      several decades ago. Most of the people in the relatively developed Chinese
      cities are developing or have developed myopia. Recently, researches reported six
      loci related to myopia. Viewing from the modern civilization and development of
      China, the sharp increase of the size of the population with myopia and the
      unbalanced change could not be explained only by gene mutation or any model of
      Mendelian inheritance. The comparison of the disparity of the economic and
      educational levels between in urban and rural areas showed that the onset of
      myopia might be influenced by both environmental and genetic factors. Special
      attention should be paid to myopia now to prevent severe physical problem in the
      Chinese urban population.

PMID- 16606605
TI  - [Histone variants and histone exchange].
AB  - Histones, as the basic components of nucleosome, are essential to chromatin
      structure and function. To adapt to various states of chromatin, corresponding
      histone variants are incorporated in nucleosome, and certain modifications also
      occur on the variants' tails. These variants change the conformation and
      stability of nucleosome to facilitate transcriptional activation or deactivation,
      DNA repairing, heterochromatin formation, and others. During histone exchange,
      chromatin remodeling complex facilitates histone variant deposition into
      nucleosome, and different variants have diverse deposition pathways. Recently,
      research on histone variants is not only a new hotspot in epigenetics, but also a
      new annotation of "histone code". In addition, histone exchange reveals new
      changing mechanism of DNA-histone interaction.

PMID- 16606606
TI  - [Progress of functional study on MRX related genes].
AB  - X-linked nonspecific mental retardation (MRX) related genes are a group of
      extensively studied genes whose mutation or deletion results in simple phenotypes
      of generalized or specific cognitive impairment in patients, such as, low
      intelligence and poor social adaptability. Studying the biological and cognitive
      functions of MRX related genes means much not only to the discovery of the
      genetic basis for non-specific MR, but also to the exploration into a new field
      of research about the molecular basis of human cognitive function. This paper
      summarizes recent progress on MRX studies, the current status and the prospect of
      this field.

PMID- 16606607
TI  - [Progress in the study on conditional male sterility in plants by genetic
      engineering].
AB  - Conditional (reversible) male sterile line in plants would be fertile under
      special conditions, and thus could be used as two-line to produce hybrid seeds.
      This paper described the strategies for creating conditional male sterile line
      and correspondingly restoring it. Some related problems about the issue were
      commented on. In addition, this review also predicted the prospects of the study
      on conditional male sterility.

PMID- 16606608
TI  - Transcriptional regulation of the Xenopus laevis Stromelysin-3 gene by thyroid
      hormone is mediated by a DNA element in the first intron.
AB  - The matrix metalloproteinase (MMP) stromelysin-3 (ST3) (MMP11) was first isolated
      as a breast cancer-associated gene and is expressed in diverse human carcinomas
      and various developmental processes involving apoptosis. The Xenopus laevis ST3
      is highly up-regulated by thyroid hormone (T3) during amphibian metamorphosis,
      and its expression is spatially and temporally correlated with apoptosis in
      different tissues. Furthermore, it has been shown in vivo and in organ cultures
      to play a critical role in regulating T3-induced epithelial cell death during
      intestinal metamorphosis. Earlier studies suggest that ST3 is a direct T3
      response gene, although a thyroid hormone response element (TRE) was not found in
      the initial analysis of the ST3 promoter. Here, we have identified a strong TRE
      consisting of two nearly perfect direct repeats of the consensus nuclear hormone
      receptor binding element AGGTCA separated by 4 bp in the first intron of the
      Xenopus ST3 gene. We show that the heterodimers of T3 receptor (TR) and 9-cis
      retinoic acid receptor bind to the TRE both in vitro and in vivo in the context
      of chromatin. Furthermore, T3 induces strong activation of the promoter through
      the intronic TRE. Interestingly, although the unliganded TR/9-cis-retinoic acid
      receptor was able to recruit corepressors to the promoter, it had little
      repressive effect on the promoter in vivo. These results suggest that the
      intronic TRE mediates the inductive effect of T3 and that promoter context plays
      an important role in gene repression by unliganded TR.

PMID- 16606609
TI  - Mechanism of cholesterol transfer from the Niemann-Pick type C2 protein to model
      membranes supports a role in lysosomal cholesterol transport.
AB  - Cells acquire cholesterol either by de novo synthesis in the endoplasmic
      reticulum or by internalization of cholesterol-containing lipoproteins,
      particularly low density lipoprotein (LDL), via receptor-mediated endocytosis.
      The inherited disorder Niemann-Pick type C (NPC), in which abnormal LDL
      cholesterol trafficking from the endo/lysosomal compartment leads to substantial
      cholesterol and glycolipid accumulation in lysosomes, is caused by defects in
      either of two genes that encode for proteins designated as NPC1 and NPC2. NPC2 is
      a small intralysosomal protein that has been characterized biochemically as a
      cholesterol binding protein. We determined the rate and mechanism by which NPC2
      delivers cholesterol to model phospholipid membranes. A fluorescence dequenching
      assay was used to monitor the kinetics of cholesterol transfer from the protein
      to membranes. The endogenous tryptophan fluorescence of the NPC2 was quenched
      upon binding of cholesterol, and the subsequent addition of acceptor vesicles
      resulted in dequenching of the tryptophan signal, enabling the monitoring of
      cholesterol transfer to membranes. The rates of cholesterol transfer were
      evaluated as a function of acceptor vesicle concentration, acceptor vesicle
      phospholipid headgroup composition, and aqueous phase properties. The results
      suggest that NPC2 rapidly transports cholesterol to phospholipid vesicles via a
      collisional mechanism which involves a direct interaction with the acceptor
      membrane. Transfer of cholesterol to membranes is faster in an acidic environment
      and is greatly enhanced by the presence of the unique lysosomal/late endosomal
      phospholipid lyso-bisphosphatidic acid (LBPA) (also known as bismonoacylglycerol
      phosphate). Finally, we found that the rate of transfer of cholesterol from
      vesicles to NPC2 was dramatically increased by the presence of lyso
      bisphosphatidic acid in the donor vesicles. These results support a role for the
      NPC2 protein in the egress of LDL derived cholesterol out of the
      endosomal/lysosomal compartment.

PMID- 16606610
TI  - Estrogen receptor alpha mediates 17alpha-ethynylestradiol causing hepatotoxicity.
AB  - Estrogens are known to cause hepatotoxicity such as intrahepatic cholestasis in
      susceptible women during pregnancy, after administration of oral contraceptives,
      or during postmenopausal replacement therapy. Enterohepatic nuclear receptors
      including farnesoid X receptor (FXR), pregnane X receptor (PXR), and constitutive
      active/androstane receptor (CAR) are important in maintaining bile acid
      homeostasis and protecting the liver from bile acid toxicity. However, no nuclear
      receptor has been implicated in the mechanism for estrogen-induced
      hepatotoxicity. Here Era(-/-), Erb(-/-), Fxr(-/-), Pxr(-/-), and Car(-/-) mice
      were employed to show that Era(-/-) mice were resistant to synthetic estrogen
      17alpha-ethynylestradiol (EE2)-induced hepatotoxicity as indicated by the fact
      that the EE2-treated Era(-/-) mice developed none of the hepatotoxic phenotypes
      such as hepatomegaly, elevation in serum bile acids, increase of alkaline
      phosphatase activity, liver degeneration, and inflammation. Upon EE2 treatment,
      estrogen receptor alpha (ERalpha) repressed the expression of bile acid and
      cholesterol transporters (bile salt export pump (BSEP), Na(+)/taurocholate
      cotransporting polypeptide (NTCP), OATP1, OATP2, ABCG5, and ABCG8) in the liver.
      Consistently, biliary secretions of both bile acids and cholesterol were markedly
      decreased in EE2-treated wild-type mice but not in the EE2-treated Era(-/-) mice.
      In addition, ERalpha up-regulated the expression of CYP7B1 and down-regulated the
      CYP7A1 and CYP8B1, shifting bile acid synthesis toward the acidic pathway to
      increase the serum level of beta-muricholic acid. ERbeta, FXR, PXR, and CAR were
      not involved in regulating the expression of bile acid transporter and
      biosynthesis enzyme genes following EE2 exposure. Taken together, these results
      suggest that ERalpha-mediated repression of hepatic transporters and alterations
      of bile acid biosynthesis may contribute to development of the EE2-induced
      hepatotoxicity.

PMID- 16606611
TI  - Differential binding of erythroid Krupple-like factor to embryonic/fetal globin
      gene promoters during development.
AB  - The competition model for beta-like globin gene switching during development
      predicts that differential binding of transcription factors to globin gene
      promoters and/or proximal enhancers regulate the competitive interactions of
      globin gene family members with the powerful locus control region (LCR). Direct
      interactions of individual genes with the LCR are essential for high level
      expression in erythroid cells. In this paper, we have demonstrated, by chromatin
      immunoprecipitation, that erythroid-Krupple-like factor (EKLF) binds to
      embryonic/fetal globin gene promoters in primitive (but not in definitive)
      erythroid cells. EKLF binds strongly to adult globin gene promoters and to LCR
      sequences HS4, HS3, HS2, and HS1 in both primitive and definitive erythroid
      cells. Trimethylation of histone H3K4 and H3K27 at the embryonic/fetal and adult
      globin gene promoters is equivalent in definitive cells; therefore, the
      differential binding of EKLF to these promoters does not appear to result from
      changes in chromatin configuration. Interestingly, the level of EKLF in
      definitive cells is 3-fold higher than the level in primitive cells. These
      results suggest that temporal-specific changes in EKLF abundance result in
      differential binding of this essential erythroid transcription factor to
      embryonic/fetal globin gene promoters during development and that these changes
      in EKLF binding specificity mediate the competitive interactions of globin gene
      family members with the LCR.

PMID- 16606612
TI  - Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis
      associated protein TRPML1.
AB  - Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder
      characterized by severe neurodegeneration, achlorhydria, and visual impairments
      such as corneal opacity and strabismus. The disease arises due to mutations in a
      group 2 transient receptor potential (TRP)-related cation channel, TRPML1.
      Mammals encode two additional TRPML proteins named TRPML2 and TRPML3. Information
      regarding the propensity of these proteins to multimerize, their subcellular
      distribution and mechanisms that regulate their trafficking are limited. Here we
      demonstrate that TRPMLs interact to form homo- and heteromultimers. Moreover, the
      presence of either TRPML1 or TRPML2 specifically influences the spatial
      distribution of TRPML3. TRPML1 and TRPML2 homomultimers are lysosomal proteins,
      whereas TRPML3 homomultimers are in the endoplasmic reticulum. However, TRPML3
      localizes to lysosomes when coexpressed with either TRPML1 or TRPML2 and is
      comparably mislocalized when lysosomal targeting of TRPML1 and TRPML2 is
      disrupted. Conversely, TRPML3 does not cause retention of TRPML1 or TRPML2 in the
      endoplasmic reticulum. These data demonstrate that there is a hierarchy
      controlling the subcellular distributions of the TRPMLs such that TRPML1 and
      TRPML2 dictate the localization of TRPML3 and not vice versa.

PMID- 16606613
TI  - One single in-frame AUG codon is responsible for a diversity of subcellular
      localizations of glutaredoxin 2 in Saccharomyces cerevisiae.
AB  - Glutaredoxins belong to a family of small proteins with glutathione-dependent
      disulfide oxidoreductase activity involved in cellular defense against oxidative
      stress. The product of the yeast GRX2 gene is a protein that is localized both in
      the cytosol and mitochondria. To throw light onto the mechanism responsible for
      the dual subcellular distribution of Grx2 we analyzed mutant constructs
      containing different targeting information. By altering amino acid residues
      around the two in-frame translation initiation start sites of the GRX2 gene, we
      could demonstrate that the cytosolic isoform of Grx2 was synthesized from the
      second AUG, lacking an N-terminal extension. Translation from the first AUG
      resulted in a long isoform carrying a mitochondrial targeting presequence. The
      mitochondrial targeting properties of the presequence and the influence of the
      mature part of Grx2 were analyzed by the characterization of the import kinetics
      of specific fusion proteins. Import of the mitochondrial isoform is relatively
      inefficient and results in the accumulation of a substantial amount of
      unprocessed form in the mitochondrial outer membrane. Substitution of Met(35),
      the second translation start site, to Val resulted in an exclusive targeting to
      the mitochondrial matrix. Our results show that a plethora of Grx2 subcellular
      localizations could spread its antioxidant functions all over the cell, but one
      single A to G [corrected] mutation converts Grx2 into a typical protein of the
      mitochondrial matrix. The "A" denotes adenine, rather than alanine, and the "G"
      refers to guanine, not glycine [corrected]

PMID- 16606614
TI  - Transcriptional profiling reveals novel markers of liver fibrogenesis: gremlin
      and insulin-like growth factor-binding proteins.
AB  - Activated hepatic stellate cells (HSC) that transdifferentiate to myofibroblasts
      in the injured liver are responsible for scar formation that leads to fibrosis
      and eventually cirrhosis. To investigate the gene expression profile during
      different stages of this process, we performed serial analysis of gene
      expression, representing a quantitative and qualitative description of all
      expressed genes. Stellate cells were isolated from human livers and cultured.
      Serial analysis of gene expression was performed on RNA isolated from quiescent,
      activated, and transdifferentiated HSC. Comparison of the three resulting
      transcriptomes showed that less than 5% of all genes changed significantly in
      expression. Established markers of liver fibrosis showed enhanced expression in
      accordance with the transdifferentiation process. In addition, induction was seen
      for several genes not yet recognized to be involved in liver fibrosis, such as
      insulin-like growth factor-binding proteins (IGFBP) and antagonists of bone
      morphogenic proteins: follistatin and gremlin. The induction of these genes was
      validated in vivo in mice developing liver fibrosis. The expression of IGFBPs and
      gremlin was measurable in the livers of these mice, whereas it was low or
      undetectable in control mice without liver fibrosis. Since gremlin modulates the
      activity of bone morphogenic growth factors, it may represent a novel pathway and
      a target for therapeutic intervention and together with IGFBPs it could be a
      specific marker of liver fibrosis. In conclusion, the comparison of the three
      transcriptomes of (activated) stellate cells reveals novel genes involved in
      fibrogenesis and provides an appreciation of the sequence and timing of the
      fibrotic process in liver.

PMID- 16606615
TI  - Analysis of nucleosome repositioning by yeast ISWI and Chd1 chromatin remodeling
      complexes.
AB  - ISWI proteins form the catalytic core of a subset of ATP-dependent chromatin
      remodeling activities in eukaryotes from yeast to man. Many of these complexes
      have been found to reposition nucleosomes but with different directionalities. We
      find that the yeast Isw1a, Isw2, and Chd1 enzymes preferentially move nucleosomes
      toward more central locations on short DNA fragments whereas Isw1b does not.
      Importantly, the inherent positioning properties of the DNA play an important
      role in determining where nucleosomes are relocated to by all of these enzymes.
      However, a key difference is that the Isw1a, Isw2, and Chd1 enzymes are unable to
      move nucleosomes to positions closer than 15 bp from a DNA end, whereas Isw1b
      can. We also find that there is a correlation between the inability of enzymes to
      move nucleosomes close to DNA ends and the preferential binding to nucleosomes
      bearing linker DNA. These observations suggest that the accessibility of linker
      DNA together with the positioning properties of the underlying DNA play important
      roles in determining the outcome of remodeling by these enzymes.

PMID- 16606616
TI  - Regulation of NR1/NR2C N-methyl-D-aspartate (NMDA) receptors by phosphorylation.
AB  - NR2C-containing N-methyl-D-aspartate (NMDA) receptors are highly expressed in
      cerebellar granule cells where they mediate the majority of current in the adult.
      NMDA receptors composed of NR1/NR2C exhibit a low conductance and reduced
      sensitivity to Mg(2+), compared with the more commonly studied NR2A- and NR2B
      containing receptors. Despite these interesting features, very little is known
      about the regulation of NR2C function. Here we investigate the role of
      phosphorylation of NR2C in regulating NMDA receptor trafficking and ion channel
      properties. We identify a phosphorylation site, serine 1244 (Ser(1244)), near the
      extreme COOH terminus of NR2C, which is phosphorylated by both cAMP-dependent
      protein kinase and protein kinase C. This residue is located adjacent to the
      consensus PDZ ligand, a region that regulates protein-protein interactions and
      receptor trafficking in NR2A and NR2B. We show that Ser(1244) on NR2C is
      phosphorylated in vitro, in heterologous cells, and in neurons. Moreover, we
      demonstrate for the first time that NR2C interacts with the PSD-95 family of PDZ
      domain-containing proteins but that phosphorylation of Ser(1244) does not
      influence this PDZ interaction. Furthermore, Ser(1244) phosphorylation does not
      regulate surface expression of NR1/NR2C receptors. However, we find that this
      site does regulate the kinetics of the ion channel: a phosphomimetic mutation at
      Ser(1244) accelerates both the rise and decay of NMDA-evoked currents in excised
      patches from HEK-293 cells. Therefore, phosphorylation of Ser(1244) does not
      regulate trafficking but unexpectedly affects ion channel function, suggesting
      that phosphorylation of Ser(1244) on NR2C may be important in defining the
      functional properties of NMDA receptor-mediated currents in the cerebellum.

PMID- 16606617
TI  - Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand
      dependent coactivator for retinoic acid receptor.
AB  - Additional sex comb-like 1 (ASXL1, 170 kDa), a mammalian homolog of Drosophila
      ASX, was identified as a protein that interacts with retinoic acid receptor (RAR)
      in the presence of retinoic acid (RA). Systematic binding assays showed that the
      C-terminal nuclear receptor box (LVMQLL) of ASXL1 and the activation function-2
      activation domain (AF-2 AD) core of the RAR are critical for ligand-dependent
      interaction. The interaction was confirmed using in vitro glutathione S
      transferase pulldown and in vivo immunoprecipitation (IP) assays. Confocal
      microscopy revealed that ASXL1 localizes in the nucleus. In addition to the
      intrinsic transactivation function of ASXL1, its cotransfection together with an
      RA-responsive luciferase reporter increased the RAR activity. This ASXL1 activity
      appears to be mediated through the functional cooperation with SRC-1, as shown by
      GST pulldown, IP, chromatin IP, and transcription assays. In the presence of
      ASXL1, more acetylated histone H3 was accumulated on the RA-responsive promoter
      in response to RA. Finally, stable expression of ASXL1 increased the expression
      of endogenous RA-regulated genes and enhanced the antiproliferative potential of
      RA. Overall, these results suggest that ASXL1 is a novel coactivator of RAR that
      cooperates with SRC-1 and implicates it as a potential antitumor target of RA in
      RA-resistant cancer cells.

PMID- 16606618
TI  - Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in
      the hippocampus.
AB  - DNA (cytosine-5) methylation represents one of the most widely used mechanisms of
      enduring cellular memory. Stable patterns of DNA methylation are established
      during development, resulting in creation of persisting cellular phenotypes.
      There is growing evidence that the nervous system has co-opted a number of
      cellular mechanisms used during development to subserve the formation of long
      term memory. In this study, we examined the role DNA (cytosine-5)
      methyltransferase (DNMT) activity might play in regulating the induction of
      synaptic plasticity. We found that the DNA within promoters for reelin and brain
      derived neurotrophic factor, genes implicated in the induction of synaptic
      plasticity in the adult hippocampus, exhibited rapid and dramatic changes in
      cytosine methylation when DNMT activity was inhibited. Moreover, zebularine and 5
      aza-2-deoxycytidine, inhibitors of DNMT activity, blocked the induction of long
      term potentiation at Schaffer collateral synapses. Activation of protein kinase C
      in the hippocampus decreased reelin promoter methylation and increased DNMT3A
      gene expression. Interestingly, DNMT activity is required for protein kinase C
      induced increases in histone H3 acetylation. Considered together, these results
      suggest that DNMT activity is dynamically regulated in the adult nervous system
      and that DNMT may play a role in regulating the induction of synaptic plasticity
      in the mature CNS.

PMID- 16606619
TI  - Subcellular localization and structural function of endogenous phosphorylated
      phosphatidylinositol 4-kinase (PI4K92).
AB  - Anti-phosphopeptide antibodies were raised against phosphatidylinositol 4-kinase
      (PI4K92) phosphorylation sites (Suer, S., Sickmann, A., Meyer, H. E., Herberg, F.
      W., and Heilmeyer, L. M. Jr. (2001) Eur. J. Biochem. 268, 2099-2106).
      Characterization proved three of them (anti-pSer-294, anti-pSer-496, and anti
      pThr-504 antibody) to be highly specific, recognizing solely PI4K92
      phosphorylated at these sites, respectively. Indirect immunofluorescence reveals
      that PI4K92 phosphorylated on Ser-294 localizes exclusively at the Golgi. The
      enzyme phosphorylated on Ser-496 and Thr-504 is detected in nuclear speckles.
      Phosphorylation of Ser-294 on PI4K92 increases the lipid kinase activity and thus
      serves better in maintaining Golgi function and morphology (compare Hausser, A.,
      Storz, P., Martens, S., Link, G., Toker, A., and Pfizenmaier, K. (2005) Nat. Cell
      Biol. 7, 880-886). Microinjection of anti-pSer-496, but not of anti-pSer-294 or
      anti-pThr-504 antibody, into the cytoplasm or into the nucleus of HS68 cells
      leads to development of hotspots, probably representing aggregated PI4K92, and in
      later stages, cells become apoptotic and finally die. The association of
      phosphorylated PI4K92 with nuclear speckles is dynamic and follows the
      morphological alteration of speckles upon inhibition of mRNA transcription with
      alpha-amanitin. Overexpressed PI4K92 phosphorylated on Ser-294 is not transported
      to the nucleus, and that phosphorylated on Ser-496 is found in the nucleus and
      mislocalized at the Golgi complex. We conclude that nuclear phosphatidylinositol
      4-phosphate, and consequently, synthesis of polyphosphoinositides are required
      for a correct nuclear function.

PMID- 16606620
TI  - Constitutive receptor-independent low density lipoprotein uptake and cholesterol
      accumulation by macrophages differentiated from human monocytes with macrophage
      colony-stimulating factor (M-CSF).
AB  - Recently, we have shown that macrophage uptake of low density lipoprotein (LDL)
      and cholesterol accumulation can occur by nonreceptor mediated fluid-phase
      macropinocytosis when macrophages are differentiated from human monocytes in
      human serum and the macrophages are activated by stimulation of protein kinase C
      (Kruth, H. S., Jones, N. L., Huang, W., Zhao, B., Ishii, I., Chang, J., Combs, C.
      A., Malide, D., and Zhang, W. Y. (2005) J. Biol. Chem. 280, 2352-2360).
      Differentiation of human monocytes in human serum produces a distinct macrophage
      phenotype. In this study, we examined the effect on LDL uptake of an alternative
      macrophage differentiation phenotype. Differentiation of macrophages from human
      monocytes in fetal bovine serum with macrophage-colony-stimulating factor (M-CSF)
      produced a macrophage phenotype demonstrating constitutive fluid-phase uptake of
      native LDL leading to macrophage cholesterol accumulation. Fluid-phase
      endocytosis of LDL by M-CSF human macrophages showed non-saturable uptake of LDL
      that did not down-regulate over 48 h. LDL uptake was mediated by continuous actin
      dependent macropinocytosis of LDL by these M-CSF-differentiated macrophages. M
      CSF is a cytokine present within atherosclerotic lesions. Thus, macropinocytosis
      of LDL by macrophages differentiated from monocytes under the influence of M-CSF
      is a plausible mechanism to account for macrophage foam cell formation in
      atherosclerotic lesions. This mechanism of macrophage foam cell formation does
      not depend on LDL modification or macrophage receptors.

PMID- 16606621
TI  - A protein in crude cytosol regulates glucose-6-phosphatase activity in crude
      microsomes to regulate group size in Dictyostelium.
AB  - Dictyostelium discoideum form groups of approximately 2 x 10(4) cells. The group
      size is regulated in part by a negative feedback pathway mediated by a secreted
      multipolypeptide complex called counting factor (CF). The CF signal transduction
      pathway involves CF-repressing internal glucose levels by increasing the K(m) of
      glucose-6-phosphatase. Little is known about how this enzyme is regulated.
      Glucose-6-phosphatase is associated with microsomes in both Dictyostelium and
      mammals. We find that the activity of glucose-6-phosphatase in crude microsomes
      from cells with high, normal, or low CF activity had a negative correlation with
      the amount of CF present in these cell lines. In crude cytosols (supernatants
      from ultracentrifugation of cell lysates), the glucose-6-phosphatase activity had
      a positive correlation with CF accumulation. The crude cytosols were further
      fractionated into a fraction containing molecules greater than 10 kDa (S>10K) and
      molecules less than 10 KDa (S<10K). S>10K from wild-type cells strongly repressed
      the activity of glucose-6-phosphatase in wild-type microsomes, whereas S>10K from
      countin(-) cells (cells with low CF activity) significantly increased the
      activity of glucose-6-phosphatase in wild-type microsomes by decreasing K(m). The
      regulatory activities in the wild-type and countin(-) S>10Ks are heat-labile and
      protease-sensitive, suggesting that they are proteins. S<10K from both wild-type
      and countin(-) cells did not significantly change glucose-6-phosphatase activity.
      Together, the data suggest that, as a part of a pathway modulating multicellular
      group size, CF regulates one or more proteins greater than 10 KDa in crude
      cytosol that affect microsome-associated glucose-6-phosphatase activity.

PMID- 16606622
TI  - hSnm1B is a novel telomere-associated protein.
AB  - Artemis, a member of the beta-CASP family, has been implicated in the regulation
      of both telomere stability and length. Prompted by this, we examined whether the
      other two putative DNA-binding members of this family, hSnm1A and hSnm1B, may
      associate with telomeres. hSnm1A was found to not interact with the telomere.
      Conversely, hSnm1B was found to associate with telomeres in vivo by both
      immunofluorescence and chromatin immunoprecipitation. Furthermore, the C terminus
      of hSnm1B was shown to interact with the TRF homology domain of TRF2 indicating
      that hSnm1B is likely recruited to the telomere via interaction with the double
      stranded telomere-binding protein TRF2.

PMID- 16606623
TI  - Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription
      of extracellular matrix-related genes and collagen accumulation in osteoblastic
      cells.
AB  - Vitamin K2 is a critical nutrient required for blood coagulation. It also plays a
      key role in bone homeostasis and is a clinically effective therapeutic agent for
      osteoporosis. We previously demonstrated that vitamin K2 is a transcriptional
      regulator of bone marker genes in osteoblastic cells and that it may potentiate
      bone formation by activating the steroid and xenobiotic receptor, SXR. To explore
      the SXR-mediated vitamin K2 signaling network in bone homeostasis, we identified
      genes up-regulated by both vitamin K2 and the prototypical SXR ligand,
      rifampicin, in osteoblastic cells using oligonucleotide microarray analysis and
      quantitative reverse transcription-PCR. Fourteen genes were up-regulated by both
      ligands. Among these, tsukushi, matrilin-2, and CD14 antigen were shown to be
      primary SXR target genes. Moreover, collagen accumulation in osteoblastic MG63
      cells was enhanced by vitamin K2 treatment. Gain- and loss-of-function analyses
      showed that the small leucine-rich proteoglycan, tsukushi, contributes to vitamin
      K2-mediated enhancement of collagen accumulation. Our results suggest a new
      function for vitamin K2 in bone formation as a transcriptional regulator of
      extracellular matrix-related genes, that are involved in the collagen assembly.

PMID- 16606624
TI  - Mitochondrial localization and putative signaling function of sucrose synthase in
      maize.
AB  - In many organisms, an increasing number of proteins seem to play two or more
      unrelated roles. Here we report that maize sucrose synthase (SUS) is distributed
      in organelles not involved in sucrose metabolism and may have novel roles beyond
      sucrose degradation. Bioinformatics analysis predicts that among the three maize
      SUS isoforms, SH1 protein has a putative mitochondrial targeting peptide (mTP).
      We validated this prediction by the immunodetection of SUS in mitochondria.
      Analysis with isoform-specific antisera revealed that both SH1 and SUS1 are
      represented in mitochondria, although the latter lacks a canonical mTP. The SUS2
      isoform is not detectable in mitochondria, despite its presence in the cytosol.
      In maize primary roots, the mitochondrion-associated SUS (mtSUS; which includes
      SH1 and SUS1) is present mostly in the root tip, indicating tissue-specific
      regulation of SUS compartmentation. Unlike the glycolytic enzymes that occur
      attached to the outside of mitochondria, SH1 and SUS1 are intramitochondrial. The
      low abundance of SUS in mitochondria, its high Km value for sucrose, and the lack
      of sucrose in mitochondria suggest that mtSUS plays a non-sucrolytic role. Co
      immunoprecipitation studies indicate that SUS interacts with the voltage
      dependent anion channel in an isoform-specific and anoxia-enhanced manner and may
      be involved in the regulation of solute fluxes into and out of mitochondria. In
      several plant species, at least one of the SUS proteins possesses a putative mTP,
      indicating the conservation of the noncatalytic function across plant species.
      Taken together, these observations suggest that SUS has a novel noncatalytic
      function in plant cells.

PMID- 16606625
TI  - A structure-based approach to retinoid X receptor-alpha inhibition.
AB  - In this paper we describe a structure-based approach designed to identify novel
      ligands for retinoid X receptor-alpha (RXRalpha). By using a virtual approach
      based on a modified scoring function, we have selected 200 potential candidates
      on the basis of their predicted ability of docking into the ligand-binding site
      of the target. Subsequent experimental verification of the compounds in in vitro
      and cell-based assays led to the identification of a number of novel high
      affinity ligands for RXRalpha. The compounds are capable of displacing 9-cis
      retinoic acid with IC(50) values in the 10 nm and 5 mum range and exhibit marked
      antagonistic activity in cellular assays. The inhibitory scaffolds discovered
      with this method form the basis for the development of novel RXRalpha ligands
      with potential therapeutic properties.

PMID- 16606626
TI  - Redox balance mechanisms in Schistosoma mansoni rely on peroxiredoxins and
      albumin and implicate peroxiredoxins as novel drug targets.
AB  - Schistosoma mansoni, a causative agent of schistosomiasis, resides in the hepatic
      portal circulation of their human host up to 30 years without being eliminated by
      the host immune attack. Production of an antioxidant "firewall," which would
      neutralize the oxidative assault generated by host immune defenses, is one
      proposed survival mechanism of the parasite. Schistosomes lack catalase, the main
      H2O2-neutralizing enzyme of many organisms, and their glutathione peroxidases are
      in the phospholipid class with poor reactivity toward H2O2. Evidence implicates
      peroxiredoxins (Prx) as providing the main enzymatic activity to reduce H2O2 in
      the parasite. Quantitative monitoring of Prx mRNAs during parasite life cycle
      indicated that Prx proteins are differentially expressed, with highest expression
      occurring in adult stages (oxidative resistant stages). Incubation of
      schistosomula with Prx1 double-stranded RNA knocked down total Prx enzymatic
      activity and resulted in lowered survival of cultured parasites compared with
      controls demonstrating that Prx are essential parasite proteins. These results
      represent the first report of lethal gene silencing in Schistosoma. Investigation
      of downstream effects of Prx silencing revealed an abrupt increase of lipid
      peroxides and the generation of several oxidized proteins. Using mass
      spectrometry, parasite albumin and actin were identified as the main oxidized
      proteins. Gene expression analysis showed that schistosome albumin was induced by
      oxidative stress. This study highlights Prx proteins as essential parasite
      proteins and potential new targets for anti-schistosome drug development and
      albumin as a novel, sacrificial oxidant scavenging protein in parasite redox
      regulation.

PMID- 16606627
TI  - The substrate radical of Escherichia coli oxygen-independent coproporphyrinogen
      III oxidase HemN.
AB  - During porphyrin biosynthesis the oxygen-independent coproporphyrinogen III
      oxidase (HemN) catalyzes the oxidative decarboxylation of the propionate side
      chains of rings A and B of coproporphyrinogen III to form protoporphyrinogen IX.
      The enzyme utilizes a 5'-deoxyadenosyl radical to initiate the decarboxylation
      reaction, and it has been proposed that this occurs by stereo-specific
      abstraction of the pro-S-hydrogen atom at the beta-position of the propionate
      side chains leading to a substrate radical. Here we provide EPR-spectroscopic
      evidence for intermediacy of the latter radical by observation of an organic
      radical EPR signal in reduced HemN upon addition of S-adenosyl-L-methionine and
      the substrate coproporphyrinogen III. This signal (g(av) = 2.0029) shows a
      complex pattern of well resolved hyperfine splittings from at least five
      different hydrogen atoms. The radical was characterized using regiospecifically
      labeled (deuterium or 15N) coproporphyrinogen III molecules. They had been
      generated from a multienzyme mixture and served as efficient substrates. Reaction
      of HemN with coproporphyrinogen III, perdeuterated except for the methyl groups,
      led to the complete loss of resolved proton hyperfine splittings. Substrates in
      which the hydrogens at both alpha- and beta-positions, or only at the beta
      positions of the propionate side chains, or those of the methylene bridges, were
      deuterated showed that there is coupling with hydrogens at the alpha-, beta-, and
      methylene bridge positions. Deuterium or 15N labeling of the pyrrole nitrogens
      without labeling the side chains only led to a slight sharpening of the radical
      signal. Together, these observations clearly identified the radical signal as
      substrate-derived and indicated that, upon abstraction of the pro-S-hydrogen atom
      at the beta-position of the propionate side chain by the 5'-deoxyadenosyl
      radical, a comparatively stable delocalized substrate radical intermediate is
      formed in the absence of electron acceptors. The observed hyperfine constants and
      g values show that this coproporphyrinogenyl radical is allylic and encompasses
      carbon atoms 3', 3, and 4.

PMID- 16606628
TI  - The role of the family in child and adolescent posttraumatic stress following
      attendance at an emergency department.
AB  - OBJECTIVE: To evaluate the role of family factors in posttraumatic stress
      symptomatology (PTSS) in children and adolescents who have attended an emergency
      department following assaults or motor vehicle accident. METHODS: Children and
      their parents completed self-report questionnaires and semistructured interviews
      relating to their psychopathology and cognitive styles at 2-4 weeks and 6 months
      after trauma. RESULTS: Parental depression was correlated with child PTSS at each
      assessment point. Less consistent findings were observed for family functioning.
      Parental endorsement of worry was a correlate of child PTSS at each assessment
      and a mediator between parental depression and child PTSS. CONCLUSIONS: A role
      for family factors, in particular parental depression and parental endorsement of
      worry, in the development of child PTSS is supported. Weaknesses of the study are
      discussed, and suggestions for future research are given.

PMID- 16606629
TI  - Screening for preschool posttraumatic stress disorder with the Child Behavior
      Checklist.
AB  - OBJECTIVE: To examine the psychometric properties and utility of a Child Behavior
      Checklist-Posttraumatic Stress Disorder (CBCL-PTSD) Scale to screen for
      posttraumatic stress disorder (PTSD) in traumatized preschool children. METHOD:
      Data for this study were drawn from a study of young child trauma and consisted
      of 62 traumatized children, 23 months through 6 years of age. The children's
      mothers were interviewed about PTSD symptoms and then completed the Child
      Behavior Checklist (CBCL). RESULTS: The modified CBCL-PTSD correlated highly with
      the number of PTSD symptoms from the interview (r = 0.66). The CBCL-PTSD scale
      predicted PTSD symptoms above and beyond the internalizing and externalizing
      scales of the CBCL. A cutoff score of nine on this scale possessed the best
      sensitivity and specificity in classifying those traumatized children who met
      diagnostic criteria for PTSD. CONCLUSION: The modified CBCL-PTSD scale could be a
      useful cost-effective tool to screen for PTSD in traumatized, preschool-age
      children.

PMID- 16606630
TI  - Polymorphisms in genes involved in GH1 release and their association with breast
      cancer risk.
AB  - The regulation of growth hormone 1 (GH1) and insulin-like-growth factor-1 (IGF-1)
      release is under the influence of three pituitary hormones [growth hormone
      releasing hormone (GHRH), ghrelin (GHRL) and somatostatin (SST)], which act in an
      autocrine/paracrine fashion in the breast. By binding to their respective
      receptors, they control cell proliferation, differentiation and apoptosis in a
      GH1/IGF-1-dependent manner. We investigated single nucleotide polymorphisms
      (SNPs) in the GHRH, GHRHR, GHRL, GHSR, SST and SSTR2 gene regions in a Polish and
      a German cohort of 798 breast cancer cases and 1011 controls. Our study revealed
      an association of a novel TC repeat polymorphism in the SST promoter with a
      decreased breast cancer risk in the Polish study population [odds ratio (OR),
      0.65; 95% confidence interval (CI), 0.44-0.96]. The closely linked SNP IVS1 A+46G
      showed the same trend. For both polymorphisms the association was stronger in
      women above the age of 50 (OR, 0.33; 95% CI, 0.14-0.76 and OR, 0.39; 95% CI, 0.18
      0.87, respectively). The protective effect of these polymorphisms was confirmed
      in a haplotype analysis among women above 50 years of age and carrying the two
      variant alleles (OR, 0.37; 95% CI, 0.17-0.80). In the independent German
      population, we observed slightly decreased ORs among women above the age of 50
      years. In the SSTR2 gene, carriers of the promoter 21/21 TG repeat genotype were
      at a decreased breast cancer risk (OR, 0.62; 95% CI, 0.41-0.94) compared to
      carriers of the other genotypes in the Polish population. Furthermore, we
      identified a protective effect of the GHRHR C-261T SNP in both populations (joint
      analysis CT+TT versus CC: OR, 0.80; 95% CI, 0.65-0.99). This effect was carried
      by a haplotype containing the protective allele. Thus, our study concludes a
      possible protective influence of distinct polymorphisms in genes involved in GH1
      release on breast cancer risk.

PMID- 16606631
TI  - Carcinogenesis and apoptosis: paradigms and paradoxes.
AB  - Apoptosis is a physiological process of cell elimination, which is important for
      both maintenance of cellular homeostasis, and cell proliferation and
      differentiation. Disturbances in the cell death process might lead to
      uncontrolled cell growth and to tumor formation. In addition, proper function of
      the apoptotic machinery is critical for tumor susceptibility to treatment. Many
      pro-apoptotic and anti-apoptotic genes have been cloned and their significance
      for the proper function of the apoptotic pathways carefully investigated.
      However, the precise role of these genes and their products in cancer development
      is less clear. Here, we will discuss some of the current paradigms and paradoxes
      concerning the involvement of apoptotic genes in carcinogenesis.

PMID- 16606632
TI  - Diverse effects of zinc on NF-kappaB and AP-1 transcription factors: implications
      for prostate cancer progression.
AB  - Nuclear factor-kappaB (NF-kappaB) and AP-1 nuclear transcriptional factors
      regulate expression of multiple genes involved in tumor growth, metastasis and
      angiogenesis; however, the relative contribution of each factor to cancer
      initiation and progression has not been established. Prostate carcinogenesis
      involves transformation of normal zinc-accumulating epithelial cells to malignant
      cells that do not accumulate zinc. Whereas activation of both NF-kappaB and AP-1
      has been implicated in prostate cancer development and growth, we tested the
      relative effects of zinc supplementation on these important transcriptional
      factors. Herein, we demonstrate that physiological levels of zinc inhibit NF
      kappaB but augment activities of AP-1 in DU-145 and PC-3 human prostate cancer
      cells. Additionally, we show that chelation of zinc with membrane-permeable zinc
      chelator, N,N,N',N',-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) abolishes
      this effect. We further propose a potential mechanism for this observation by
      demonstrating that zinc supplementation induces phosphorylation of the members of
      three major MAPK subfamilies regulating AP-1 and NF-kappaB activation (ERK 1/2,
      JNK and p38) while blocking TNF-alpha-mediated degradation of the inhibitory
      subunit I kappa B alpha and nuclear translocation of RelA in prostate cancer
      cells. VEGF, IL-6, IL-8 and MMP-9 are major pro-angiogenic and pro-metastatic
      molecules whose promoter regions contain binding sites for both NF-kappaB and AP
      1. These cytokines have been associated with negative prognostic features in
      prostate cancer. We demonstrate that treatment of human prostate cancer cell
      lines with zinc reduces expression of VEGF, IL-6, IL-8 and MMP-9. We further show
      that zinc reduces expression of intercellular adhesion molecule-1 and
      functionally suppresses tumor cell invasiveness and adhesion. Therefore, the
      ability of zinc supplementation to inhibit NF-kappaB supercedes zinc-mediated
      activation of AP-1 family members. Upregulation of intracellular zinc levels may
      have important implications for inhibiting the angiogenic and metastatic
      potentials of malignant cells, predominantly through suppression of NF-kappaB
      signaling.

PMID- 16606633
TI  - The function of peroxiredoxins in plant organelle redox metabolism.
AB  - In 1996, cDNA sequences referred to as plant peroxiredoxins (Prx), i.e. a 1-Cys
      Prx and a 2-Cys Prx, were reported from barley. Ten years of research have
      advanced our understanding of plant Prx as thiol-based peroxide reductases with a
      broad substrate specificity, ranging from hydrogen peroxide to alkyl
      hydroperoxides and peroxinitrite. Prx have several features in common. (i) They
      are abundant proteins that are routinely detected in proteomics approaches. (ii)
      They interact with proteins such as glutaredoxins, thioredoxins, and cyclophilins
      as reductants, but also non-dithiol-disulphide exchange proteins. By work with
      transgenic plants, their activity was shown to (iii) affect metabolic integrity,
      (iv) protect DNA from damage in vitro and as shown here in vivo, and (v) modulate
      intracellular signalling related to reactive oxygen species and reactive nitrogen
      species. (vi) In all organisms Prx are encoded by small gene families that are of
      particular complexity in higher plants. A comparison of the Prx gene families in
      rice and Arabidopsis thaliana supports previous suggestions on Prx function in
      specific subcellular and metabolic context. (vii) Prx gene expression and
      activity are subjected to complex regulation realized by an integration of
      various signalling pathways. 2-Cys Prx expression depends on redox signals,
      abscisic acid, and protein kinase cascades. Besides these general properties, the
      chloroplast Prx have acquired specific roles in the context of photosynthesis.
      The thioredoxin-dependent peroxidase activity can be measured in crude plant
      extracts and contributes significantly to the overall H(2)O(2) detoxification
      capacity. Thus organellar Prx proteins enable an alternative water-water cycle
      for detoxification of photochemically produced H(2)O(2), which acts independently
      from the ascorbate-dependent Asada-Halliwell-Foyer cycle. 2-Cys Prx and Prx Q
      associate with thylakoid membrane components. The mitochondrial PrxII F is
      essential for root growth under stress. Following a more general introduction,
      the paper summarizes present knowledge on plant organellar Prx, addressing Prx in
      signalling, and also suggests some lines for future research.

PMID- 16606634
TI  - Identification of new gene expression regulators specifically expressed during
      plant seed maturation.
AB  - A cDNA-AFLP approach on Linum usitatissimum (flax) was used to identify genes
      specifically expressed during the seed maturation process. Among the 20,000 cDNA
      AFLP tags produced, 486 were selected for their seed-specific expression during
      maturation. When compared with the publicly available databases, half of them
      presented some significant similarity with known plant sequences. The results
      obtained confirmed the accuracy of the approach as numerous genes previously
      described as being expressed exclusively in plant seeds were identified in this
      screen. The focus was on sequences similar to plant regulators involved in the
      control of gene expression, either at the transcriptional, post-transcriptional,
      or post-translational levels. Using a real-time RT-PCR approach, seed-specific
      expression kinetics were confirmed for 13 of these regulators that were never
      characterized for being expressed during seed maturation. Among these, a flax
      gene of the non-LEC1-like HAP3 family and a flax MYB factor were shown to be
      expressed in specialized tissues of flax embryo using an in situ hybridization
      approach. By expression kinetic comparison between these flax genes and their
      Arabidopsis counterparts, it was found that the new HAP3 gene should be related
      to a ubiquitous seed maturation mechanism, while a new MYB factor appears to be
      related to a more seed-specific maturation mechanism. These results demonstrate
      the utility of the flax database in not only identifying new genes expressed
      during seed maturation but also in being able to highlight the distinction
      between conserved and non-conserved seed maturation mechanisms.

PMID- 16606635
TI  - Production of the cryptic EefABC efflux pump in Enterobacter aerogenes
      chloramphenicol-resistant mutants.
AB  - OBJECTIVES: AcrAB-TolC is the major tripartite multidrug efflux pump in
      Enterobacter aerogenes while EefABC is a cryptic efflux system. This study was
      conducted to identify and characterize E. aerogenes mutants producing the EefABC
      efflux pump. METHODS: Four spontaneous chloramphenicol-resistant (CMR) mutants
      were isolated. The expression level of the eefABC promoter and the production of
      the EefA and B proteins were analysed in the mutants. Antibiotic susceptibilities
      were compared for wild-type and mutant strains. Efflux activity was investigated
      using an efflux pump inhibitor. RESULTS: The activation of the eefABC promoter
      was detected in four CMR mutants. These mutants showed increased resistance to
      erythromycin and ticarcillin, but not to fluoroquinolones, ketolides and
      detergents. Two additional efflux proteins were detected in the mutants. The CMR
      mutants bear no mutation in hns, which encodes a repressor of eefABC. No
      alteration of porin expression, a phenotype observed in marA or ramA multidrug
      resistant mutants, was detected in the mutants. CONCLUSIONS: These observations
      suggest that eefABC activation can occur in vitro independently of the H-NS, MarA
      or RamA global regulators.

PMID- 16606636
TI  - Lopinavir/ritonavir exposure in treatment-naive HIV-infected children following
      twice or once daily administration.
AB  - OBJECTIVES: Lopinavir/ritonavir is approved for treatment of HIV-infected
      children at a dosage regimen of 230/57.5 mg/m(2) twice daily. However, once daily
      administration could increase convenience and patient adherence. Our study aimed
      at evaluating whether inhibitory concentrations are maintained in plasma
      following administration of lopinavir/ritonavir once daily. PATIENTS AND METHODS:
      Lopinavir/ritonavir was administered at the standard twice daily regimen to 21
      HIV-infected children, as a component of their antiretroviral treatment.
      Following at least 1 month of administration, seven patients received a dose of
      460/115 mg/m(2) once daily for three consecutive days. After the third dose of
      once daily administration, blood samples were drawn at the following times: 0
      (pre-dose), 1, 2 and 4 h following administration. The pre-dose (C(min)) and the
      peak (C(max)) concentrations were compared with the values obtained following
      twice daily administration in all the study patients. RESULTS: Median
      (interquartile range) C(min) with the once daily regimen was 1.59 (0.77-6.85)
      mg/L versus 7.90 (5.45-9.77) mg/L with the twice daily regimen (P < 0.05). C(min)
      was considered inhibitory for wild-type virus (>1.0 mg/L) in four out of seven
      patients. C(max) did not differ significantly between the once daily and twice
      daily regimens. CONCLUSIONS: Our small pilot study suggests that
      lopinavir/ritonavir once daily may be a suitable regimen for antiretroviral-naive
      children. However, due to the high interindividual variability and low
      concentrations in some patients, therapeutic drug monitoring may be necessary to
      ensure that concentrations are adequate to inhibit viral replication. A formal
      clinical study of lopinavir/ritonavir once daily in treatment-naive children is
      warranted.

PMID- 16606637
TI  - Key questions in antiretroviral therapy: Italian Consensus Workshop (2005).
AB  - A panel of leading Italian specialists in infectious diseases, virologists and
      immunologists met in Rome in 2005 to review critical data and discuss
      recommendations for each of the key questions in antiretroviral therapy today:
      When to start treatment? How to start? When to switch? What to switch to? Whether
      to stop or not to stop treatment, and how? The method of a nominal group meeting
      was used and recommendations were graded for their strength and quality using a
      system based on the one adopted by the Infectious Diseases Society of America.
      Main conclusions are summarized and critically discussed in this consensus
      statement, as well as some of the most recent data supporting these
      recommendations are provided.

PMID- 16606638
TI  - The 'balance intervention' for promoting caloric compensatory behaviours in
      response to overeating: a formative evaluation.
AB  - To help people prevent weight gain, the Netherlands Nutrition Centre initiated
      the 'balance intervention', which promotes moderation of food intake and/or
      increased physical activity in response to occasions of overeating. The aim of
      this study was to determine whether intervention materials were appreciated,
      encouraged information seeking and increased motivation and caloric compensatory
      behaviours. A three-group randomized trial with pre-intervention measures (n =
      963, response 86%) and post-intervention measures (n = 857) using electronic
      questionnaires was conducted among participants aged 25-40 years, recruited from
      an Internet research panel. The first group received a printed brochure and
      electronic newsletters (print group), the second group was exposed to radio
      advertisements (radio group) and the third group was the control group. Multiple
      regression analyses were used to investigate the impact of the materials on self
      reported prevalence of overeating, attitudes, perceived behavioural control,
      intentions and compensatory behaviours. At follow-up, we found significantly more
      positive attitudes, intentions and dietary action in the print and radio groups.
      However, participants who received the radio advertisement had a significantly
      lower perceived behavioural control. No effects were found on the prevalence of
      overeating. The results indicate that the intervention materials have potential
      for increasing people's attitudes, motivation and self-reported behaviour
      actions, with a possible negative side-effect on perceived behavioural control.

PMID- 16606639
TI  - Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive
      appendix tissue samples from a retrospective prevalence study.
AB  - OBJECTIVE: To perform prion protein gene (PRNP) codon 129 analysis in DNA
      extracted from appendix tissue samples that had tested positive for disease
      associated prion protein. DESIGN: Reanalysis of positive cases identified in a
      retrospective anonymised unlinked prevalence study of variant Creutzfeldt-Jakob
      disease (vCJD) in the United Kingdom. STUDY SAMPLES: Three positive appendix
      tissue samples out of 12,674 samples of appendix and tonsil tested for disease
      associated prion protein. The patients from whom these samples were obtained were
      aged 20-29 years at the time of surgery, which took place in 1996-9. SETTING:
      Pathology departments in two tertiary centres in England and Scotland. RESULTS:
      Adequate DNA was available for analysis in two of the three specimens, both of
      which were homozygous for valine at codon 129 in the PRNP. CONCLUSIONS: This is
      the first indication that the valine homozygous subgroup at codon 129 in the PRNP
      is susceptible to vCJD infection. All tested clinical cases of vCJD have so far
      occurred in the methionine homozygous subgroup, and a single case of probable
      iatrogenic vCJD infection has been identified in one patient who was a
      methionine/valine heterozygote at this genetic locus. People infected with vCJD
      with a valine homozygous codon 129 PRNP genotype may have a prolonged incubation
      period, during which horizontal spread of the infection could occur either from
      blood donations or from contaminated surgical instruments used on these
      individuals during the asymptomatic phase of the illness.

PMID- 16606640
TI  - Interobserver agreement and intraobserver reproducibility of embryo quality
      assessments.
AB  - BACKGROUND: The objective of this investigation was to determine the inter- and
      intraobserver agreement when assessing embryo quality. METHODS: This
      investigation included 4002 cleaved embryos from 7535 oocytes retrieved in 688
      patients undergoing IVF cycles in a multicentre trial. Embryos were evaluated
      locally at the inverted microscope at 28, 44 and 68 h (+/-1 h) post-insemination.
      Digital images of the embryos were assessed centrally by three blinded
      embryologists. To assess reproducibility, 215 randomly selected cleaved embryos
      from 33 patients were re-evaluated by the three central embryologists. RESULTS:
      The interobserver agreement among the central embryologists (using the same
      method of evaluation; 2D images) was good for classification of top-quality
      embryos (kappa 0.71-0.73), excellent for classification of normally developed
      embryos (kappa 0.83-0.86) and good-excellent for classification of transferable
      embryos (kappa 0.78-0.82). The interobserver agreement between local and
      consolidated central assessment (different methods of evaluation, inverted
      microscopy versus 2D images) was good for all three embryo classifications (kappa
      0.64-0.79). The intraobserver reproducibility for all three overall embryo
      classifications was excellent for the consolidated central assessment (kappa 0.80
      0.91). CONCLUSION: Embryo quality can be determined with a good degree of
      interobserver agreement independently of the method of evaluation. Embryologists
      classify embryos with excellent intraobserver reproducibility.

PMID- 16606641
TI  - Retinoids during the in vitro transition from bovine morula to blastocyst.
AB  - BACKGROUND: The conversion of retinol (ROH) to retinoic acid (RA) is crucial
      during development but has been not studied during blastocyst formation. METHODS
      AND RESULTS: In vitro-produced bovine morulae were treated for 24 h with citral
      (which inhibits the synthesis of RA from ROH), citral + all trans retinoic acid
      (ATRA), ATRA or no additives. Citral interfered with blastocyst development,
      whereas exogenous RA had no effect. RA, however, reversed the effect of citral on
      development and stimulated cell proliferation. Neither citral nor RA changed the
      apoptotic index, but RA triggered an increase in the apoptotic frequency of the
      inner cell mass. Citral and RA reduced the necrotic index. Na/K-ATPase alpha1
      subunit mRNA concentrations (analysed by real-time PCR) increased after hatching
      and showed dependence on retinoid activity, but no evidence was found of any
      retinoid effect on p53 expression. Nevertheless, the p53 mRNA concentration
      increased in response to proliferation in hatched blastocysts. CONCLUSION: The
      preimplantation bovine embryo metabolizes endogenous ROH to RA, which
      participates in important cell processes. The true extent of the influence of RA
      is unknown, although the modulation of retinoid metabolism seems to be a means of
      increasing cell proliferation. This knowledge might be used to improve embryo
      quality and the efficiency of stem cell derivation.

PMID- 16606642
TI  - A.R.T. and history, 1678-1978.
AB  - Louise Brown, the first baby conceived after IVF, was born on 25 July 1978 and
      turned 27 last year. From one perspective, her birth can be seen as the
      culmination of 300 years of medical and scientific investigation aimed at
      understanding the fascinating process of reproduction. This essay was written as
      a tribute to mark the unique contribution to assisted reproductive technology
      (ART) which resulted from the collaboration of a scientist, Bob Edwards, and a
      clinician, Patrick Steptoe, who pioneered the successful clinical use of IVF.
      This article was not intended to be a conventional history of science, but
      instead has primarily focused on those early discoveries which in the author's
      opinion were critical to our current understanding of mammalian reproduction.
      There are some digressions and many omissions necessitated by attempting to cover
      300 years in a relatively short essay. In particular, there is no mention of
      endocrinology because this area has been covered in numerous reviews and books.
      The main sources of historical information for this article were the
      authoritative books of Professor Cole (1930), Dr Elizabeth Gasking (1967),
      Professor John Farley (1982), Dr Fielding H. Garrison (1929) and the
      Philosophical Transactions of The Royal Society or Letters collated from the
      latter.

PMID- 16606643
TI  - Prenatal exposure to 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p'-DDE) in
      relation to child growth.
AB  - OBJECTIVE: To examine the relation between prenatal 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethylene (p,p'-DDE) exposure (a metabolite of the insecticide DDT)
      and child growth during the first 7 years of life. Design Prospective cohort
      study. Participants 1,712 children born between 1959 and 1966 with measured p,p'
      DDE concentrations in their mother's serum samples from pregnancy. Setting
      Multicenter US Collaborative Perinatal Project (CPP). RESULTS: The highest
      prenatal concentrations of p,p'-DDE (>or=60 microg/l), as compared with the
      lowest (<15 microg/l), were associated with decreased height at age 1 year
      [adjusted coefficient (SE) = -0.72 cm (0.37), n = 1,540], 4 years [-1.14 cm
      (0.56), n = 1,289], and 7 years [-2.19 (0.46), n = 1,371]. Among subjects in
      lower categories of exposure no association was observed. CONCLUSIONS: The
      findings suggest that high prenatal exposure to p,p'-DDE decreases height in
      children. Impaired growth may be a general indicator of toxicity and suggests
      that specific organ systems (e.g. endocrine) could be affected.

PMID- 16606644
TI  - No signs of immunoactivation in the cerebrospinal fluid during treatment with
      infliximab.
AB  - Neuroinflammatory (demyelinating) disease is a rare but feared complication of
      treatment with anti-tumour necrosis factor (TNF)alpha in patients with
      polyarthritis. In this study, blood and cerebrospinal fluid markers of
      inflammation were analysed in 10 people with polyarthritis before and during
      treatment with infliximab. An increased systemic expression of interferon
      (IFN)gamma was detected. Systemic administration of IFNgamma is known to
      exacerbate multiple sclerosis. However, the present study failed to detect signs
      of inflammation in the cerebrospinal fluid samples-that is, pleocytosis,
      oligoclonal immunoglobulin G bands, increased expression of IFNgamma, TNFalpha or
      interleukin 10, or increased levels of nitric oxide oxidation products. Our
      initial hypothesis, that the few cases of clinical neuroinflammatory disorders
      observed during treatment of polyarthritis with anti-TNFalpha represent the
      extreme end of a commonly occurring minor intrathecal immune activation, which in
      most cases does not give any overt neurological dysfunction, was not supported.
      Induction of systemic IFNgamma production may still be relevant in
      neuroinflammation associated with treatment with anti-TNFalpha.

PMID- 16606645
TI  - Polymorphism at position +896 of the toll-like receptor 4 gene interferes with
      rapid response to treatment in rheumatoid arthritis.
AB  - The aim of this study was to determine whether the +896 A-->G substitution of the
      Toll-like receptor 4 (TLR4) gene, causing the Asp299-->Gly change in the
      extracellular domain of TLR4, influences treatment response in recent-onset
      rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from
      the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were
      treated either with only one disease-modifying antirheumatic drug (DMARD) with or
      without prednisolone (single group), or with three DMARDs and prednisolone
      (combination group). Patients homozygotic for the wild-type +896A allele were
      compared with those having the polymorphic G allele in terms of early clinical
      response (at 6 months) by the 28-joint Disease Activity Score (DAS28). 1 of 20
      (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with
      TLR4 +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in
      remission (p = 0.001). DAS28 of the single group with TLR4 +896AG or GG was
      higher than with AA (p = 0.019). In the combination group, remission rates and
      DAS28 values were comparable between the genotypes. The polymorphic TLR4 +896G
      allele may impair treatment response to single DMARD treatment in recent-onset
      rheumatoid arthritis.

PMID- 16606646
TI  - Efficacy of sulfasalazine in patients with inflammatory back pain due to
      undifferentiated spondyloarthritis and early ankylosing spondylitis: a
      multicentre randomised controlled trial.
AB  - OBJECTIVES: To assess the effect of sulfasalazine (SSZ) on inflammatory back pain
      (IBP) due to active undifferentiated spondyloarthritis (uSpA) or ankylosing
      spondylitis in patients with symptom duration <5 years. METHODS: Patients with
      IBP and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >3 from 12
      centres were randomly assigned to 24 weeks' treatment with SSZ 2 g/day or
      placebo. The primary outcome variable was the change in BASDAI over 6 months.
      Secondary outcomes included measures of spinal pain, physical function and
      inflammation. RESULTS: 230 patients (50% men, age range 18-64 years, 67% human
      leucocyte antigen B27 positive) were treated with either SSZ 2x1 g/day or placebo
      for 6 months. Enthesitis was found in 50%, and peripheral arthritis in 47% of the
      patients. The mean (SD) BASDAI dropped markedly in both groups: by 3.7 (2.7) and
      3.8 (2.4), respectively, as did most secondary outcome measures. No noticeable
      difference in treatment was observed between groups. Patients with IBP and no
      peripheral arthritis had significantly (p = 0.03) more benefit with SSZ (BASDAI
      5.1 (1.3) to 2.8 (2.3)) than with placebo (5.2 (1.6) to 3.8 (2.4)). Spinal pain
      (p = 0.03) and morning stiffness (p = 0.05) improved with SSZ in these patients,
      but other secondary outcomes were not markedly different. CONCLUSION: SSZ was no
      better than placebo for the treatment of the signs and symptoms of uSpA; however,
      SSZ was more effective than placebo in the subgroup of patients with IBP and no
      peripheral arthritis.

PMID- 16606647
TI  - Familial Mediterranean fever (FMF) and beyond: a new horizon. Fourth
      International Congress on the Systemic Autoinflammatory Diseases held in
      Bethesda, USA, 6-10 November 2005.
AB  - Autoinflammatory diseases are characterised by seemingly unprovoked inflammation.
      They can be categorised as: hereditary (monogenic) autoinflammatory diseases,
      complex (polygenic/multifactorial) autoinflammatory diseases, and diseases where
      the course is affected by mutations in the defined autoinflammatory disease
      genes. Identification of the inflammatory pathways involved has opened up new
      areas of research which have implications for the treatment of these disorders
      and the pathogenesis of common inflammatory diseases.

PMID- 16606648
TI  - The Met66 allele of the functional Val66Met polymorphism in the brain-derived
      neurotrophic factor gene confers protection against neurocognitive dysfunction in
      systemic lupus erythematosus.
AB  - BACKGROUND: A common functional polymorphism of the brain-derived neurotrophic
      factor gene (BDNF Val66Met) was previously associated with diminished episodic
      memory performance in healthy people. As cognitive function is commonly impaired
      in patients with systemic lupus erythematosus (SLE), the association of the BDNF
      Val66Met with neurocognitive function was studied. OBJECTIVE: To study the
      association of the BDNF Val66Met with neurocognitive function in a cohort of
      patients with SLE. METHODS: Cognitive function was assessed in 59 patients with
      SLE with no previous or current central nervous system involvement. Cognitive
      tests were grouped into five domains (memory, attention/executive function,
      visuospatial skills, motor function and psychomotor speed) and used to obtain
      domain Z scores, reflecting the difference between averaged scores of performance
      on individual tests and published norms in each domain. Genotyping was carried
      out using a 5'-nuclease assay with 99.9% accuracy. Unpaired t test was used to
      assess the relationship between genotypes and cognitive function, whereas the
      effect of possible confounders was assessed in a multivariate analysis. RESULTS:
      Patients carrying the Met66 allele scored significantly higher on psychomotor,
      attention/executive and motor function tests, resulting in significantly higher
      domain Z scores for the psychomotor (p = 0.005) and motor (p = 0.002) domains.
      CONCLUSIONS: The BDNF Met66 allele was associated with better cognitive
      functioning in the psychomotor and motor domains, even after controlling for
      differences in ethnicity, sex, depression status and prednisone treatment. These
      data suggest that the BDNF Met66 allele confers protection against the decline of
      motor and psychomotor cognitive functions in patients with longstanding SLE.

PMID- 16606649
TI  - Diagnostic and predictive value of anti-cyclic citrullinated protein antibodies
      in rheumatoid arthritis: a systematic literature review.
AB  - OBJECTIVE: To evaluate the two generations of anti-cyclic citrullinated protein
      (CCP) antibodies as a diagnostic marker of rheumatoid arthritis (RA) and as a
      predictor of future development of RA in healthy subjects and in patients with
      early undifferentiated arthritis. METHODS: A systematic analysis of the
      literature published between 1999 and February 2006 was conducted. Data were
      collected on the sensitivity and specificity of the two generations of anti-CCP
      antibodies for diagnosing RA and predicting future development of the disease.
      RESULTS: Among 107 studies initially identified, 68 had interpretable data and
      were analysed. Diagnostic properties were assessed in 58 studies: mean (SD)
      sensitivity was 53 (10)% (range 41-68) and 68 (15)% (range 39-94) for anti-CCP1
      and anti-CCP2, respectively; mean (SD) specificity was 96 (3)% (range 90-99) and
      95 (5)% (range 81-100) for anti-CCP1 and anti-CCP2, respectively. Predictive
      properties were assessed in 14 studies; odds ratio (95% confidence interval) of
      anti-CCP1 and anti-CCP2 for the future development of RA were 20 (14 to 31) and
      25 (18 to 35), respectively, among patients with early undifferentiated arthritis
      and 64.5 (8.5 to 489) and 28 (8 to 95), respectively, among healthy subjects.
      CONCLUSION: Sensitivity of the second generation of anti-CCP is close to that of
      rheumatoid factor, with a higher specificity, for distinguishing RA from other
      rheumatic diseases. Moreover, anti-CCP antibodies appear to be highly predictive
      of the future development of RA in both healthy subjects and patients with
      undifferentiated arthritis.

PMID- 16606650
TI  - Enrichment of CD4+ CD25high T cell population in patients with systemic lupus
      erythematosus treated with glucocorticoids.
AB  - OBJECTIVES: To characterise and quantify the CD4+ CD25+ T cell population in
      patients with systemic lupus erythematosus (SLE) and to detect the possible
      influence of treatments and clinical manifestations. METHODS: Characterisation of
      CD25(low) and CD25(high) CD4+ T cells from healthy controls and from patients
      with SLE was carried out using flow cytometry, analysing the expression of
      activation and differentiation markers. The percentage of both circulating cell
      subsets was determined in 56 controls and 110 unselected patients with SLE. Data
      were related to treatment during the past 3 months and to various clinical
      manifestations. RESULTS: CD4+ CD25(high) lymphocytes from controls expressed low
      levels of CD69, CD154 or CD30, but also expressed glucocorticoid-induced tumour
      necrosis factor receptor, high levels of intracellular cytotoxin T lymphocyte
      associated antigen 4, CD45RO and diminished amounts of CD4, all of which are
      phenotypic characteristics of natural regulatory T cells. CD4+ CD25(low) cells,
      on the other hand, expressed the highest levels of activation markers, indicating
      that they represent recently activated effector cells. Similarly, analysis of
      cells from patients with SLE showed the same two phenotypically distinguishable
      CD4+ CD25(low) and CD4+ CD25(high) populations, although both expressed slightly
      increased levels of activation markers. Quantitative analysis showed a
      considerably raised percentage of CD25(low) and, especially, CD25(high) cells in
      patients with SLE compared with controls. This increment was unrelated to
      clinical manifestations, but correlated with glucocorticoid treatment. Patients
      treated with glucocorticoids presented raised levels of CD25(high) cells, whereas
      untreated patients and those with anti-malarial or immunosuppressive drugs had
      levels similar to those in controls. CONCLUSIONS: The percentage of CD4+
      CD25(high) cells was not altered in non-steroid-treated patients, whereas
      glucocorticoid treatment increased their frequency in patients with SLE.

PMID- 16606651
TI  - Etanercept and sulfasalazine, alone and combined, in patients with active
      rheumatoid arthritis despite receiving sulfasalazine: a double-blind comparison.
AB  - OBJECTIVE: To compare the efficacy and safety of etanercept and sulfasalazine,
      alone and in combination, in patients with active rheumatoid arthritis despite
      sulfasalazine treatment. METHODS: A double-blind, randomised study in adult
      patients with active rheumatoid arthritis despite stable sulfasalazine (2-3
      g/day) treatment. The primary end point was a 20% response by the American
      College of Rheumatology (ACR) criteria at 24 weeks. RESULTS: At baseline, the
      three treatment groups (sulfasalazine, n = 50; etanercept, n = 103; etanercept
      and sulfasalazine, n = 101) were comparable for demographic variables and disease
      activity. Lack of efficacy was the primary reason for discontinuation
      (sulfasalazine, n = 12; etanercept, n = 1; etanercept and sulfasalazine, n = 4;
      p<0.001). Significantly more patients receiving etanercept, alone or in
      combination (74% for each), achieved ACR 20 responses at 24 weeks than those
      receiving sulfasalazine (28%; p<0.01). Similarly, more patients in the etanercept
      groups achieved ACR 50 and ACR 70 responses than those in the sulfasalazine group
      (p<0.01). In the groups receiving etanercept, significant differences in the ACR
      core components were observed by week 2 compared with those receiving
      sulfasalazine alone (p<0.01). The incidences of several common adverse events
      (headache, nausea, asthenia) were lower with etanercept alone than with the
      combination (p<0.05), but infections and injection site reactions were higher
      with etanercept alone (p<0.05). The safety profiles of both etanercept treatment
      groups were comparable with previous experience of etanercept. CONCLUSIONS: For
      all efficacy variables assessed, etanercept alone or in combination with
      sulfasalazine resulted in substantial and similar improvement in disease activity
      from baseline to week 24 compared with sulfasalazine alone in patients with
      active rheumatoid arthritis despite their sulfasalazine treatment. All three
      treatments were generally well tolerated.

PMID- 16606652
TI  - Long-term outcome in polymyositis and dermatomyositis.
AB  - BACKGROUND: Although polymyositis and dermatomyositis are regarded as treatable
      disorders, prognosis is not well known, as in the literature long-term outcome
      and prognostic factors vary widely. AIM: To analyse the prognostic outcome
      factors in polymyositis and adult dermatomyositis. METHODS: We determined
      mortality, clinical outcome (muscle strength, disability, persistent use of drugs
      and quality of life) and disease course and analysed prognostic outcome factors.
      RESULTS: Disease-related death occurred in at least 10% of the patients, mainly
      because of associated cancer and pulmonary complications. Re-examination of 110
      patients after a median follow-up of 5 years showed that 20% remained in
      remission and were off drugs, whereas 80% had a polycyclic or chronic continuous
      course. The cumulative risk of incident connective tissue disorder in patients
      with myositis was significantly increased. 65% of the patients had normal
      strength at follow-up, 34% had no or slight disability, and 16% had normal
      physical sickness impact profile scores. Muscle weakness was associated with
      higher age (odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3 to 10.3).
      Disability was associated with male sex (OR 3.1; 95% CI 1.2 to 7.9). 41% of the
      patients with a favourable clinical outcome were still using drugs. Jo-1
      antibodies predicted the persistent use of drugs (OR 4.4, 95% CI 1.3 to 15.0).
      CONCLUSIONS: Dermatomyositis and polymyositis are serious diseases with a disease
      related mortality of at least 10%. In the long term, myositis has a major effect
      on perceived disability and quality of life, despite the regained muscle
      strength.

PMID- 16606653
TI  - Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor
      activator of the NFkappaB ligand serum levels during treatment with infliximab in
      patients with rheumatoid arthritis.
AB  - OBJECTIVES: To examine whether treatment with anti-tumour necrosis factor (TNF)
      alpha prevents loss of bone mineral density (BMD) at the spine and hip
      (generalised) and in the hands (local) of patients with rheumatoid arthritis, and
      to study the changes in markers of bone metabolism, including receptor activator
      of the NFkappaB ligand (RANKL) and osteoprotegerin (OPG), during anti-TNF
      treatment. PATIENTS AND METHODS: 102 patients with active rheumatoid arthritis,
      who were treated with infliximab during 1 year, were included in this open cohort
      study. The BMD of the spine and hip (dual x ray absorptiometry) and hands dual x
      ray radiogrammetry was measured before the start of treatment and after 1 year.
      Changes in osteocalcin formation, beta-isomerised carboxy terminal telopeptide of
      type 1 collagen (beta-CTx, resorption), RANKL and OPG were determined at 0, 14,
      30 and 46 weeks. RESULTS: The BMD of the spine and hip was unchanged during
      treatment with infliximab, whereas BMD of the hand decreased significantly by
      0.8% (p<0.01). The BMD of the hip in patients with a good European League Against
      Rheumatism response showed a favourable change compared with patients not
      achieving such a response. Serum beta-CTx and RANKL were both considerably
      decreased compared with baseline at all time points. The decrease in beta-CTx was
      associated with the decrease in Disease Activity Score of 28 joints and C
      reactive protein during the 0-14 weeks interval. CONCLUSION: In patients with
      rheumatoid arthritis treated with infliximab, spine and hip bone loss is
      arrested, whereas metacarpal cortical hand bone loss is not stopped. The outcome
      of the study also supports a relationship between clinical response, in terms of
      reduced inflammatory activity, and changes in bone loss of the spine, hip and
      hands.

PMID- 16606654
TI  - Angiographically proven coronary artery disease in scleroderma.
AB  - OBJECTIVE: It has been suggested that macrovascular disease is more common in
      patients with scleroderma (SSc). We investigated the prevalence of coronary
      artery disease (CAD) in SSc using coronary angiography. METHODS: Coronary
      angiography was performed in 172 patients with SSc and suspected CAD to examine
      the prevalence of significant CAD. The prevalence of CAD was estimated in the
      whole group and also according to age, gender and type of symptoms (typical
      angina, atypical angina and non-anginal pain or breathlessness). Standardized
      prevalence ratios (SPRs) were calculated in each symptomatic group in order to
      compare CAD rates amongst our observed population with those predicted using the
      Diamond and Forrester (D & F) probability analysis. This analysis provides an
      estimate of the probability of CAD based on gender, age and symptoms in subjects
      aged between 30-69 yrs. RESULTS: The observed prevalence of CAD in the whole
      population was 22% (38/172); 17% (6/36) in males and 23% (32/136) in females. A
      total of 41 patients were excluded because they were outside the age range for D
      & F analysis. Compared with the reference population, the SPRs for CAD in the
      three SSc groups were: 47% (95% CI 21.7-89.9) in the typical angina group (22
      patients), 50% (95% CI 13.6-128) in the atypical angina group (22 patients) and
      93% (95% CI 49.4-158.8) in the non-anginal pain or breathlessness group (87
      patients). CONCLUSION: The prevalence of CAD in patients with SSc is similar and
      not greater to that expected in individuals without SSc.

PMID- 16606655
TI  - Acetaminophen, like conventional NSAIDs, may reduce synovitis in osteoarthritic
      knees.
AB  - OBJECTIVE: To determine the extent to which treatment of patients with
      symptomatic knee osteoarthritis (OA) with non-steroidal anti-inflammatory drugs
      (NSAIDs) and acetaminophen (ACET) reduces total effusion volume and synovial
      tissue volume, as quantified by magnetic resonance imaging (MRI). METHODS:
      Sequential pilot studies used subjects whose knee OA was treated with NSAIDs
      (n=10) or with ACET <or=4 g/day (n=20), respectively. After a five half-lives
      washout of their pain medication, the OA knee with the higher pain score >or=15
      of 25 on the Western Ontario and McMaster Universities' pain scale underwent l.5T
      MRI. Effusion was quantified in axial short tau inversion recovery images; to
      measure synovial tissue volume, fat-suppressed T1-weighted axial images were
      obtained 3 min after i.v. injection of gadolinium contrast. After the initial MRI
      examination, patients resumed their customary pain medications until the severity
      of knee pain returned to baseline, when pain was again measured and the MRI was
      repeated. RESULTS: Pain severity after washout was similar in subjects taking
      ACET and NSAIDs. Reinstitution of ACET resulted in a 50% decrease in the mean of
      pain scores (P=1.7 x 10(-12)) that was comparable with that seen after the
      reinstitution of NSAID (49%, P=6.0 x 10(-7)). The mean total effusion volume
      measured during the flare of knee pain induced by the withdrawal of the two drugs
      was comparable (ACET 16.9 ml, NSAID 16.2 ml; P=0.884). Significant decreases in
      mean total effusion volume were observed after reinstitution of both ACET (-4.5
      ml, P=0.009) and NSAID (-3.3 ml, P=0.013); the difference between drugs was not
      significant. Analyses of synovial volume yielded similar results. CONCLUSION:
      While uncontrolled and derived from small samples, these data suggest that ACET
      may have a significant anti-inflammatory effect in patients with knee OA,
      comparable with that achieved with NSAIDs, possibly through an effect on
      neurogenic inflammation. Joint pain is the clinical feature of OA that most often
      leads the affected individual to seek medical attention. Because many patients
      with OA improve symptomatically with the use of NSAIDs, it has been widely
      assumed that the pain of OA is due to synovial inflammation. However, the origins
      of OA pain are numerous and may vary from patient to patient and, within the same
      subject, from visit to visit. Although the articular cartilage is usually the
      site of the most obvious pathological changes in this disease, it is aneural and,
      therefore, is not the source of joint pain. However, in addition to the synovium,
      the subchondral bone, joint capsule, osteophytes, menisci, ligaments,
      periarticular tendons, entheses and bursae all contain nociceptive nerve endings,
      stimulation of which by chemical or physical mediators may be a basis for OA
      pain.

PMID- 16606656
TI  - EURADOS 2005 Annual Meeting and Scientific Symposium on Progress in Radiation
      Protection Dosimetry and Dosimetry for Medical Applications.

PMID- 16606658
TI  - New Al2O3:C,Mg crystals for radiophotoluminescent dosimetry and optical imaging.
AB  - Optical and dosimetric properties of a new radiophotoluminescent material based
      on aluminum oxide doped with carbon and magnesium (Al2O3:C,Mg) and having
      aggregate oxygen vacancy defects are presented. The Al2O3:C,Mg crystals are
      characterized by several new optical absorption and emission bands. It is
      suggested that the main optical properties of this material are due to the
      formation of aggregate defects composed of two oxygen vacancies and two Mg
      impurity atoms. Radiation-induced optical absorption bands are centered at 335
      and 620 nm and produce fluorescent emission at 750 nm with a 75 +/- 5 ns
      lifetime. The dose measurements are performed by illumination of the Al2O3:C,Mg
      crystal with 335 nm or 650 nm light and by measuring the intensity of the 750 nm
      fluorescence. The detector material is insensitive to room light before and after
      the irradiation and the traps are stable up to 600 degrees C. A dose measurement
      range between 5 mGy and 200 Gy, suitable for therapeutic radiology applications,
      was demonstrated. The short luminescent lifetime and nondestructive readout is
      favorable for imaging applications.

PMID- 16606659
TI  - In situ long-term monitoring system for radioactive contaminants.
AB  - A long-term in situ subsurface instrument for monitoring radioactive contaminant
      plumes, as an alternative to soil analysis, is described. A portable, laser-based
      reader optically stimulates luminescence from sensors, each containing an Al2O3:C
      dosemeter. The sensors, designed for placement at various subsurface locations
      around a waste site, are allowed to accumulate dose for a predetermined time that
      is based on the instrument's minimum detectable dose (MDD). The reader is then
      attached to the sensor by fibre optic cable to read the accumulated dose; an
      increase above natural background levels indicating the presence of leaked
      radioactivity. Based on an MDD of 5 microGy, it is shown that the sensor can
      measure soil concentrations of 1.85 Bq cm(-3) after an exposure time of 50 h for
      137Cs and 67 h for 90Sr/90Y. Discrimination between beta and gamma radiation is
      possible using an end cap placed over one of the two paired sensors, allowing
      simultaneous measurement of 137Cs and 90Sr/90Y in a mixed field. The monitor
      system represents a substantial improvement over quarterly soil sampling because
      of a greatly increased measurement frequency and the ability to perform
      measurements reproducibly.

PMID- 16606660
TI  - Dose distribution in the Russian Segment of the International Space Station.
AB  - Absorbed dose and average linear energy transfer (LET) were assessed by means of
      (7)LiF:Mg,Ti (TLD-700) thermoluminescent (TL) detectors for different panels on
      board the Russian Segment of the International Space Station in the timeframe
      between March and November 2002 (233 d). A technique is presented to correct the
      measured absorbed dose values for TL efficiency in the radiation climate on-board
      the spacecraft. Average LET is determined from the high-temperature TL emission
      in the TLD-700 glow curve and used as a parameter in the TL efficiency
      correction. Depending on the shielding distribution, the efficiency-corrected
      absorbed dose varies between 154 +/- 5 microGy d(-1) in panel no. 327 (core block
      ceiling) and 191 +/- 3 microGy d(-1) in panel no. 110 (core block central axis,
      floor). The experimental data are compared with the model calculations by using
      detailed shielding distributions and orbit parameters as inputs.

PMID- 16606661
TI  - EX vivo ESR measurements associated with Monte Carlo calculations for accident
      dosimetry: application to the 2001 Georgian accident.
AB  - Electron spin resonance (ESR) spectroscopy and the Monte Carlo (MC) technique
      were jointly applied to the physical dose reconstruction of the accident that
      occurred on 2 December 2001 in Georgia. Three people were exposed to two very
      high-activity (2.6 x 10(15) Bq) 90Sr sources. Following this exposure, the two
      most seriously affected victims exhibited severe radiological injuries localised
      in the back as well as a haematopoietic syndrome. The information concerning the
      circumstances of the accident in terms of sequences of irradiation and the
      exposure time was not clearly established. The physical dose reconstruction of
      the accident was performed for one victim, treated in France, using both MC
      simulations and ESR measurements made on one vertebra and two rib samples removed
      from the victim for medical reasons. The complementary nature of the two tools
      made it possible to estimate the dose distribution within the body with
      reasonable accuracy and helped to develop the treatment strategy.

PMID- 16606662
TI  - External dosimetry in the aftermath of a radiological terrorist event.
AB  - This paper reviews external dosimetry in emergency preparedness planning for a
      potential terrorist release of radioactive material in a densely populated area.
      The radiation dose received by response workers and members of the public is
      needed to understand health risks. The existing framework for dosimetry of
      routinely occupationally exposed workers is not directly applicable to all
      emergency workers who would respond to a radiological terrorist event. Emergency
      preparedness plans incorporate various old and new dosimetry technologies,
      including quartz fibre electrets, electronic dosemeters, personnel badges and
      wallet cards. Environmental monitoring and dose calculations are the usual
      methods for determining public dose. However, during the late-phase response,
      after removable contamination has been eliminated, it may be easier and more
      straightforward to provide individual dosimetry for members of the public who may
      be moving through a city with varying contamination areas. Doing so could allow
      resumption of normal activities earlier and promote confidence in reusing the
      site.

PMID- 16606663
TI  - Improvements in CVD diamond properties for radiotherapy dosimetry.
AB  - The goal of this work was to compare the behaviour of a chemical vapour deposited
      (CVD) diamond sample, grown at the University of Florence using a local
      procedure, with that of a commercial CVD diamond. The comparison was performed
      exposing both systems to 25 MV photons and measuring the current response during
      irradiation. Properties of dosimetric interest such as stability of response,
      dose rate dependence and rise time were investigated. After a preliminary study,
      which evidenced better performances of the commercial device with respect to the
      local CVD diamond, the latter was irradiated with a high fluence of fast
      neutrons. As a result of the neutron treatment, the quality of the CVD home-made
      diamond has been improved to match with that of the commercial dosemeter.

PMID- 16606664
TI  - Physiological pathway of differentiation of hematopoietic stem cell population
      into mural cells.
AB  - Endothelial cells (ECs), which are a major component of blood vessels, have been
      reported to develop in adulthood from hematopoietic cell populations, especially
      those of the monocyte lineage. Here we show that mural cells (MCs), another
      component of blood vessels, develop physiologically during embryogenesis from a
      hematopoietic stem cell (HSC) population, based on the in vitro culture of HSCs
      and histological examination of acute myeloid leukemia 1 mutant embryos, which
      lack HSCs. As in the embryo, HSCs in adult bone marrow differentiate into
      CD45+CD11b+ cells before differentiating into MCs. Moreover, CD45+CD11b+ cells
      are composed of two populations, CD11bhigh and CD11blow cells, both of which can
      differentiate into MCs as well as ECs. Interestingly, in a murine ischemia model,
      MCs and ECs derived from the CD11blow population had a long-term potential to
      contribute to the formation of newly developed blood vessels in vivo compared
      with the CD11high population, which could not. Moreover, injection of the
      CD11bhigh population induced leaky blood vessels, but the CD11blow population did
      not. With respect to the permeability of vessels, we found that angiopoietin 1,
      which is a ligand for Tie2 receptor tyrosine kinase expressed on ECs and is
      suggested to induce cell adhesion between ECs and MCs, is produced by the
      CD11blow population and plays a critical role in the formation of nonleaky
      vessels. These observations suggested that the CD11low cell population serves as
      a good source of cells for in vivo blood vessel regeneration.

PMID- 16606665
TI  - Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells.
AB  - The role of innate immune recognition by intestinal epithelial cells (IECs) in
      vivo is ill-defined. Here, we used highly enriched primary IECs to analyze Toll
      like receptor (TLR) signaling and mechanisms that prevent inappropriate
      stimulation by the colonizing microflora. Although the lipopolysaccharide (LPS)
      receptor complex TLR4/MD-2 was present in fetal, neonatal, and adult IECs, LPS
      induced nuclear factor kappaB (NF-kappaB) activation and chemokine (macrophage
      inflammatory protein 2 [MIP-2]) secretion was only detected in fetal IECs. Fetal
      intestinal macrophages, in contrast, were constitutively nonresponsive to LPS.
      Acquisition of LPS resistance was paralleled by a spontaneous activation of IECs
      shortly after birth as illustrated by phosphorylation of IkappaB-alpha and
      nuclear translocation of NF-kappaB p65 in situ as well as transcriptional
      activation of MIP-2. Importantly, the spontaneous IEC activation occurred in
      vaginally born mice but not in neonates delivered by Caesarean section or in TLR4
      deficient mice, which together with local endotoxin measurements identified LPS
      as stimulatory agent. The postnatal loss of LPS responsiveness of IECs was
      associated with a posttranscriptional down-regulation of the interleukin 1
      receptor-associated kinase 1, which was essential for epithelial TLR4 signaling
      in vitro. Thus, unlike intestinal macrophages, IECs acquire TLR tolerance
      immediately after birth by exposure to exogenous endotoxin to facilitate
      microbial colonization and the development of a stable intestinal host-microbe
      homeostasis.

PMID- 16606666
TI  - B7-H4 expression identifies a novel suppressive macrophage population in human
      ovarian carcinoma.
AB  - Tumor-associated macrophages are a prominent component of ovarian cancer stroma
      and contribute to tumor progression. B7-H4 is a recently identified B7 family
      molecule. We show that primary ovarian tumor cells express intracellular B7-H4,
      whereas a fraction of tumor macrophages expresses surface B7-H4. B7-H4+ tumor
      macrophages, but not primary ovarian tumor cells, suppress tumor-associated
      antigen-specific T cell immunity. Blocking B7-H4-, but not arginase-, inducible
      nitric oxide synthase or B7-H1 restored the T cell stimulating capacity of the
      macrophages and contributes to tumor regression in vivo. Interleukin (IL)-6 and
      IL-10 are found in high concentrations in the tumor microenvironment. These
      cytokines stimulate macrophage B7-H4 expression. In contrast,
      granulocyte/macrophage colony-stimulating factor and IL-4, which are limited in
      the tumor microenvironment, inhibit B7-H4 expression. Ectopic expression of B7-H4
      makes normal macrophages suppressive. Thus, B7-H4+ tumor macrophages constitute a
      novel suppressor cell population in ovarian cancer. B7-H4 expression represents a
      critical checkpoint in determining host responses to dysfunctional cytokines in
      ovarian cancer. Blocking B7-H4 or depleting B7-H4+ tumor macrophages may
      represent novel strategies to enhance T cell tumor immunity in cancer.

PMID- 16606667
TI  - Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic
      inflammation in the gastrointestinal tract.
AB  - The cytokine interleukin (IL) 25 has been implicated in the initiation of type 2
      immunity by driving the expression of type 2 cytokines such as IL-5 and IL-13,
      although its role in the regulation of immunity and infection-induced
      inflammation is unknown. Here, we identify a dual function for IL-25: first, in
      promoting type 2 cytokine-dependent immunity to gastrointestinal helminth
      infection and, second, in limiting proinflammatory cytokine production and
      chronic intestinal inflammation. Treatment of genetically susceptible mice with
      exogenous IL-25 promoted type 2 cytokine responses and immunity to Trichuris. IL
      25 was constitutively expressed by CD4+ and CD8+ T cells in the gut of mouse
      strains that are resistant to Trichuris, and IL-25-deficient mice on a
      genetically resistant background failed to develop a type 2 immune response or
      eradicate infection. Furthermore, chronically infected IL-25(-/-) mice developed
      severe infection-induced intestinal inflammation associated with heightened
      expression of interferon-gamma and IL-17, identifying a role for IL-25 in
      limiting pathologic inflammation at mucosal sites. Therefore, IL-25 is not only a
      critical mediator of type 2 immunity, but is also required for the regulation of
      inflammation in the gastrointestinal tract.

PMID- 16606668
TI  - Identification of an interleukin (IL)-25-dependent cell population that provides
      IL-4, IL-5, and IL-13 at the onset of helminth expulsion.
AB  - Type 2 immunity, which involves coordinated regulation of innate and adaptive
      immune responses, can protect against helminth parasite infection, but may lead
      to allergy and asthma after inappropriate activation. We demonstrate that il25(-/
      ) mice display inefficient Nippostrongylus brasiliensis expulsion and delayed
      cytokine production by T helper 2 cells. We further establish a key role for
      interleukin (IL)-25 in regulating a novel population of IL-4-, IL-5-, IL-13
      producing non-B/non-T (NBNT), c-kit+, FcepsilonR1- cells during helminth
      infection. A deficit in this population in il25(-/-) mice correlates with
      inefficient N. brasiliensis expulsion. In contrast, administration of recombinant
      IL-25 in vivo induces the appearance of NBNT, c-kit+, FcepsilonR1- cells and
      leads to rapid worm expulsion that is T and B cell independent, but type 2
      cytokine dependent. We demonstrate that these IL-25-regulated cells appear
      rapidly in the draining lymph nodes, implicating them as a source of type 2
      cytokines during initiation of worm expulsion.

PMID- 16606669
TI  - Cytosolic recognition of flagellin by mouse macrophages restricts Legionella
      pneumophila infection.
AB  - To restrict infection by Legionella pneumophila, mouse macrophages require Naip5,
      a member of the nucleotide-binding oligomerization domain leucine-rich repeat
      family of pattern recognition receptors, which detect cytoplasmic microbial
      products. We report that mouse macrophages restricted L. pneumophila replication
      and initiated a proinflammatory program of cell death when flagellin contaminated
      their cytosol. Nuclear condensation, membrane permeability, and interleukin-1beta
      secretion were triggered by type IV secretion-competent bacteria that encode
      flagellin. The macrophage response to L. pneumophila was independent of Toll-like
      receptor signaling but correlated with Naip5 function and required caspase 1
      activity. The L. pneumophila type IV secretion system provided only pore-forming
      activity because listeriolysin O of Listeria monocytogenes could substitute for
      its contribution. Flagellin monomers appeared to trigger the macrophage response
      from perforated phagosomes: once heated to disassemble filaments, flagellin
      triggered cell death but native flagellar preparations did not. Flagellin made L.
      pneumophila vulnerable to innate immune mechanisms because Naip5+ macrophages
      restricted the growth of virulent microbes, but flagellin mutants replicated
      freely. Likewise, after intratracheal inoculation of Naip5+ mice, the yield of L.
      pneumophila in the lungs declined, whereas the burden of flagellin mutants
      increased. Accordingly, macrophages respond to cytosolic flagellin by a mechanism
      that requires Naip5 and caspase 1 to restrict bacterial replication and release
      proinflammatory cytokines that control L. pneumophila infection.

PMID- 16606670
TI  - Tissue expression of PD-L1 mediates peripheral T cell tolerance.
AB  - Programmed death 1 (PD-1), an inhibitory receptor expressed on activated
      lymphocytes, regulates tolerance and autoimmunity. PD-1 has two ligands: PD-1
      ligand 1 (PD-L1), which is expressed broadly on hematopoietic and parenchymal
      cells, including pancreatic islet cells; and PD-L2, which is restricted to
      macrophages and dendritic cells. To investigate whether PD-L1 and PD-L2 have
      synergistic or unique roles in regulating T cell activation and tolerance, we
      generated mice lacking PD-L1 and PD-L2 (PD-L1/PD-L2(-/-) mice) and compared them
      to mice lacking either PD-L. PD-L1 and PD-L2 have overlapping functions in
      inhibiting interleukin-2 and interferon-gamma production during T cell
      activation. However, PD-L1 has a unique and critical role in controlling self
      reactive T cells in the pancreas. Our studies with bone marrow chimeras
      demonstrate that PD-L1/PD-L2 expression only on antigen-presenting cells is
      insufficient to prevent the early onset diabetes that develops in PD-L1/PD-L2(-/
      ) non-obese diabetic mice. PD-L1 expression in islets protects against
      immunopathology after transplantation of syngeneic islets into diabetic
      recipients. PD-L1 inhibits pathogenic self-reactive CD4+ T cell-mediated tissue
      destruction and effector cytokine production. These data provide evidence that PD
      L1 expression on parenchymal cells rather than hematopoietic cells protects
      against autoimmune diabetes and point to a novel role for PD-1-PD-L1 interactions
      in mediating tissue tolerance.

PMID- 16606671
TI  - Endogenous factors enhance HIV infection of tissue naive CD4 T cells by
      stimulating high molecular mass APOBEC3G complex formation.
AB  - Human immunodeficiency virus (HIV) can infect resting CD4 T cells residing in
      lymphoid tissues but not those circulating in peripheral blood. The molecular
      mechanisms producing this difference remain unknown. We explored the potential
      role of the tissue microenvironment and its influence on the action of the
      antiviral factor APOBEC3G (A3G) in regulating permissivity to HIV infection. We
      found that endogenous IL-2 and -15 play a key role in rendering resident naive
      CD4 T cells susceptible to HIV infection. Infection of memory CD4 T cells also
      requires endogenous soluble factors, but not IL-2 or -15. A3G is found in a high
      molecular mass complex in HIV infection-permissive, tissue-resident naive CD4 T
      cells but resides in a low molecular mass form in nonpermissive, blood-derived
      naive CD4 T cells. Upon treatment with endogenous soluble factors, these cells
      become permissive for HIV infection, as low molecular mass A3G is induced to
      assemble into high molecular mass complexes. These findings suggest that in
      lymphoid tissues, endogenous soluble factors, likely including IL-2 and -15 and
      others, stimulate the formation of high molecular mass A3G complexes in tissue
      resident naive CD4 T cells, thereby relieving the potent postentry restriction
      block for HIV infection conferred by low molecular mass A3G.

PMID- 16606672
TI  - Regulation of osteoclast function and bone mass by RAGE.
AB  - The receptor for advanced glycation end products (RAGE) is a member of the
      immunoglobulin superfamily that has multiple ligands and is implicated in the
      pathogenesis of various diseases, including diabetic complications,
      neurodegenerative disorders, and inflammatory responses. However, the role of
      RAGE in normal physiology is largely undefined. Here, we present evidence for a
      role of RAGE in osteoclast maturation and function, which has consequences for
      bone remodeling. Mice lacking RAGE had increased bone mass and bone mineral
      density and decreased bone resorptive activity in vivo. In vitro-differentiated
      RAGE-deficient osteoclasts exhibited disrupted actin ring and sealing zone
      structures, impaired maturation, and reduced bone resorptive activity. Impaired
      signaling downstream of alphavbeta3 integrin was observed in RAGE(-/-) bone
      marrow macrophages and precursors of OCs. These results demonstrate a role for
      RAGE in osteoclast actin cytoskeletal reorganization, adhesion, and function, and
      suggest that the osteosclerotic-like phenotype observed in RAGE knockout mice is
      due to a defect in osteoclast function.

PMID- 16606673
TI  - Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is
      independent of free radical scavenging.
AB  - Oxidative stress is implicated in atherogenesis, yet most clinical trials with
      antioxidants, particularly vitamin E, have failed to protect against
      atherosclerotic diseases. A striking exception is probucol, which retards
      atherosclerosis in carotid arteries and restenosis of coronary arteries after
      angioplasty. Because probucol has in vitro cellular-protective effects
      independent of inhibiting lipid oxidation, we investigated the mode of action of
      probucol in vivo. We used three models of vascular disease: apolipoprotein E
      deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model
      of restenosis; and carotid injury in obese Zucker rats, a model of type 2
      diabetes. Unexpectedly, we observed that the phenol moieties of probucol were
      insufficient, whereas its sulphur atoms were required for protection. Probucol
      and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue,
      protected via cell-specific effects on inhibiting macrophage accumulation,
      stimulating reendothelialization, and inhibiting vascular smooth muscle cell
      proliferation. These processes were mediated via induction of heme oxygenase-1
      (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the
      molecular target of probucol. They indicate 2-electron rather than radical (1
      electron) oxidants as important contributors to atherogenesis, and point to novel
      lead compounds for therapeutic intervention against atherosclerotic diseases.

PMID- 16606674
TI  - Loss of SOCS3 in T helper cells resulted in reduced immune responses and
      hyperproduction of interleukin 10 and transforming growth factor-beta 1.
AB  - Suppressor of cytokine signaling (SOCS)3 is a major negative feedback regulator
      of signal transducer and activator of transcription (STAT)3-activating cytokines.
      Transgenic mouse studies indicate that high levels of SOCS3 in T cells result in
      type 2 T helper cell (Th2) skewing and lead to hypersensitivity to allergic
      diseases. To define the physiological roles of SOCS3 in T cells, we generated T
      cell-specific SOCS3 conditional knockout mice. We found that the mice lacking
      SOCS3 in T cells showed reduced immune responses not only to ovalbumin-induced
      airway hyperresponsiveness but also to Leishmania major infection. In vitro,
      SOCS3-deficient CD4+ T cells produced more transforming growth factor (TGF)-beta1
      and interleukin (IL)-10, but less IL-4 than control T cells, suggesting
      preferential Th3-like differentiation. We found that STAT3 positively regulates
      TGF-beta1 promoter activity depending on the potential STAT3 binding sites.
      Furthermore, chromatin immunoprecipitation assay revealed that more STAT3 was
      recruited to the TGF-beta1 promoter in SOCS3-deficient T cells than in control T
      cells. The activated STAT3 enhanced TGF-beta1 and IL-10 expression in T cells,
      whereas the dominant-negative form of STAT3 suppressed these. From these
      findings, we propose that SOCS3 regulates the production of the immunoregulatory
      cytokines TGF-beta1 and IL-10 through modulating STAT3 activation.

PMID- 16606675
TI  - Evidence for discrete stages of human natural killer cell differentiation in
      vivo.
AB  - Human natural killer (NK) cells originate from CD34(+) hematopoietic progenitor
      cells, but the discrete stages of NK cell differentiation in vivo have not been
      elucidated. We identify and functionally characterize, from human lymph nodes and
      tonsils, four NK cell developmental intermediates spanning the continuum of
      differentiation from a CD34(+) NK cell progenitor to a functionally mature NK
      cell. Analyses of each intermediate stage for CD34, CD117, and CD94 cell surface
      expression, lineage differentiation potentials, capacity for cytokine production
      and natural cytotoxicity, and ETS-1, GATA-3, and T-BET expression provide
      evidence for a new model of human NK cell differentiation in secondary lymphoid
      tissues.

PMID- 16606676
TI  - Antigen recognition strength regulates the choice between extrafollicular plasma
      cell and germinal center B cell differentiation.
AB  - B cells responding to T-dependent antigen either differentiate rapidly into
      extrafollicular plasma cells or enter germinal centers and undergo somatic
      hypermutation and affinity maturation. However, the physiological cues that
      direct B cell differentiation down one pathway versus the other are unknown. Here
      we show that the strength of the initial interaction between B cell receptor
      (BCR) and antigen is a primary determinant of this decision. B cells expressing a
      defined BCR specificity for hen egg lysozyme (HEL) were challenged with sheep red
      blood cell conjugates of a series of recombinant mutant HEL proteins engineered
      to bind this BCR over a 10,000-fold affinity range. Decreasing either initial BCR
      affinity or antigen density was found to selectively remove the extrafollicular
      plasma cell response but leave the germinal center response intact. Moreover,
      analysis of competing B cells revealed that high affinity specificities are more
      prevalent in the extrafollicular plasma cell versus the germinal center B cell
      response. Thus, the effectiveness of early T-dependent antibody responses is
      optimized by preferentially steering B cells reactive against either high
      affinity or abundant epitopes toward extrafollicular plasma cell differentiation.
      Conversely, responding clones with weaker antigen reactivity are primarily
      directed to germinal centers where they undergo affinity maturation.

PMID- 16606677
TI  - Lipoprotein oxidation in cardiovascular disease: chief culprit or innocent
      bystander?
AB  - Oxidation of low-density lipoprotein (LDL) is thought to contribute to
      atherosclerosis and cardiovascular disease. Consistent with this idea, the
      antioxidant drug probucol reduces the risk of restenosis, a form of
      cardiovascular disease, in humans. However, a new study now suggests that the
      protective effect of probucol depends not on its ability to inhibit lipid
      oxidation, but on its ability to induce the stress-induced antiinflammatory
      enzyme heme oxygenase (HO)-1. This might explain why other antioxidants, such as
      vitamin E, fail to prevent cardiovascular disease in humans.

PMID- 16606678
TI  - New battlefields for costimulation.
AB  - Costimulation regulates the activation of naive T cells as they first encounter
      antigens in the secondary lymphoid organs. But recently characterized
      costimulatory molecules of the B7 family appear to have roles beyond initial T
      cell activation. New evidence shows that negative costimulators expressed by
      tumors and normal tissues afford local protection from T cell-mediated attack.

PMID- 16606679
TI  - Helper T cell differentiation enters a new era: le roi est mort; vive le roi!
AB  - In the dark ages of T cell biology, we considered two fates for differentiated
      CD4+ T cells: T helper (Th)1 and Th2 cells. Now we know that the reality is much
      more complex and interesting. The newest Th cell subset produces the cytokine IL
      17. New evidence shows that the IL-17-related cytokine IL-25 is essential for Th2
      responses in two infectious disease models.

PMID- 16606680
TI  - Herpes simplex virus central nervous system relapse during treatment of infantile
      spasms with corticotropin.
AB  - Here we report an infant who had herpes simplex virus (HSV) encephalitis and
      sustained severe bilateral damage to the posterior frontal lobes, postcentral
      gyri, and the thalami despite intravenous acyclovir treatment. At 7 months of
      age, the patient developed infantile spasms and was treated with corticotropin
      injections. After 10 days of corticotropin treatment, she developed lethargy,
      fever, and opisthotonic posturing. Her cerebrospinal fluid again was positive for
      HSV DNA, indicating recurrent HSV encephalitis, and repeat MRI revealed new
      lesions of the right frontal, parietal, temporal, and occipital lobes.
      Immunosuppression by corticotropin may have led to the reactivation of the HSV
      encephalitis. Corticotropin should be relatively contraindicated for use when a
      patient has a history of HSV infection, or intravenous acyclovir should be
      administered concurrently.

PMID- 16606681
TI  - Pneumonia and empyema caused by penicillin-resistant Neisseria meningitidis: a
      case report and literature review.
AB  - Pneumonia is an uncommon manifestation of Neisseria meningitidis infection, and
      empyema is rarely reported. Uniform penicillin susceptibility has been assumed
      for meningococcal infections for many years, but decreased penicillin
      susceptibility has been recognized recently with increasing frequency.
      Breakpoints to define different categories of susceptibility were published
      recently by the Clinical and Laboratory Standards Institute. We report the case
      of a teenage girl with sepsis and extensive bilateral pneumonia with empyema
      caused by an N meningitidis isolate that was resistant to penicillin. Her
      protracted clinical course suggested that penicillin resistance contributed to
      her delayed recovery. Our experience with this patient suggests that
      susceptibility testing should be performed in every case of N meningitidis
      isolation, and treatment with a third-generation cephalosporin should be provided
      until the susceptibility results are known. Clinical suspicion of N meningitidis
      as a possible cause of respiratory symptoms accompanied by hypotension, even in
      the absence of a rash, may aid in diagnosis and therefore in the treatment and
      provision of prophylaxis to contacts of patients with meningococcal disease.

PMID- 16606682
TI  - Reduction in neonatal mortality in Chile between 1990 and 2000.
AB  - OBJECTIVE: Our objective with this article was to describe the declining trend in
      neonatal mortality in Chile between 1990 and 2000 and examine potential causal
      factors. METHODS: Descriptive analysis of data that were provided by the Chilean
      Ministry of Health on all approximately 2,900,000 births occurred in Chile
      between 1990 and 2000. Total neonatal mortality rates (<28 days), and birth
      weight-specific and gestational age-specific mortality rates from 1990 to 2000
      were analyzed by year. Public health interventions that were implemented during
      the 1990s were reviewed to assess their potential influence on the observed
      trends in neonatal mortality. RESULTS: The neonatal mortality rate between 1990
      and 2000 decreased from 8.3 to 5.7 per 1000 live births. This decline was not
      associated with decreases in the proportion of low birth weight and preterm
      infants but rather with declines in birth weight-specific and gestational age
      specific mortality rates. Examination of the trends in birth weight-specific and
      gestational age-specific mortality rates showed that a marked proportional
      decrease in mortality rates was achieved among infants who weighed <1500 g and
      were delivered before 32 weeks. It is plausible, both biologically and
      temporally, that the observed trends in the reduction in birth weight-specific
      and gestational age-specific mortality rates are associated with the introduction
      of specific sector-wide interventions that aim to improve newborn care in very
      preterm and low birth weight infants. CONCLUSIONS: Important reductions in
      newborn mortality in developing countries are possible with the implementation of
      effective neonatal care interventions.

PMID- 16606683
TI  - Improved scoring of functional groups from gene expression data by decorrelating
      GO graph structure.
AB  - MOTIVATION: The result of a typical microarray experiment is a long list of genes
      with corresponding expression measurements. This list is only the starting point
      for a meaningful biological interpretation. Modern methods identify relevant
      biological processes or functions from gene expression data by scoring the
      statistical significance of predefined functional gene groups, e.g. based on Gene
      Ontology (GO). We develop methods that increase the explanatory power of this
      approach by integrating knowledge about relationships between the GO terms into
      the calculation of the statistical significance. RESULTS: We present two novel
      algorithms that improve GO group scoring using the underlying GO graph topology.
      The algorithms are evaluated on real and simulated gene expression data. We show
      that both methods eliminate local dependencies between GO terms and point to
      relevant areas in the GO graph that remain undetected with state-of-the-art
      algorithms for scoring functional terms. A simulation study demonstrates that the
      new methods exhibit a higher level of detecting relevant biological terms than
      competing methods.

PMID- 16606684
TI  - Analysis assistant for single-molecule force spectroscopy data on membrane
      proteins--MPTV.
AB  - Force-distance (F-D) curves of single membrane proteins reveal information on
      inter- and intramolecular interactions occurring within a protein and between
      proteins. However, the analysis of single-molecule force spectroscopy data is a
      time consuming and complex process requiring objective criteria. In most cases
      the user requires additional information to interpret F-D curves. Therefore we
      developed a software assistant representing the force or molecular interaction
      pattern and the topology or the 3D structure of the membrane protein. This
      representation establishes a basis for detailed interpretation of the protein
      structure and its underlying molecular interactions. Various integrated
      bioinformatic features further assist in the interpretation of measured and
      assigned molecular interactions that determine membrane protein folding,
      structure, stability and function. Web queries and programs about the topology
      are directly linked. Motifs, helix types, representation of Venn diagrams and the
      complete functionality of the program Jmol belong to it. AVAILABILITY: The
      program MPTV is freely available from the website at
      http://www.bioforscher.de/mptv.htm/.

PMID- 16606685
TI  - ArrayCluster: an analytic tool for clustering, data visualization and module
      finder on gene expression profiles.
AB  - SUMMARY: One of the significant challenges in gene expression analysis is to find
      unknown subtypes of several diseases at the molecular levels. This task can be
      addressed by grouping gene expression patterns of the collected samples on the
      basis of a large number of genes. Application of commonly used clustering methods
      to such a dataset however are likely to fail owing to over-learning, because the
      number of samples to be grouped is much smaller than the data dimension which is
      equal to the number of genes involved in the dataset. To overcome such
      difficulty, we developed a novel model-based clustering method, referred to as
      the mixed factors analysis. The ArrayCluster is a freely available software to
      perform the mixed factors analysis. It provides us some analytic tools for
      clustering DNA microarray experiments, data visualization and an automatic
      detector for module transcriptional of genes that are relevant to the calibrated
      molecular subtypes and so on.

PMID- 16606686
TI  - AuberGene--a sensitive genome alignment tool.
AB  - MOTIVATION: The accumulation of genome sequences will only accelerate in the
      coming years. We aim to use this abundance of data to improve the quality of
      genomic alignments and devise a method which is capable of detecting regions
      evolving under weak or no evolutionary constraints. RESULTS: We describe a genome
      alignment program AuberGene, which explores the idea of transitivity of local
      alignments. Assessment of the program was done based on a 2 Mbp genomic region
      containing the CFTR gene of 13 species. In this region, we can identify 53% of
      human sequence sharing common ancestry with mouse, as compared with 44% found
      using the usual pairwise alignment. Between human and tetraodon 93 orthologous
      exons are found, as compared with 77 detected by the pairwise human-tetraodon
      comparison. AuberGene allows the user to (1) identify distant, previously
      undetected, conserved orthogonal regions such as ORFs or regulatory regions; (2)
      identify neutrally evolving regions in related species which are often overlooked
      by other alignment programs; (3) recognize false orthologous genomic regions. The
      increased sensitivity of the method is not obtained at the cost of reduced
      specificity. Our results suggest that, over the CFTR region, human shares 10%
      more sequence with mouse than previously thought ( approximately 50%, instead of
      40% found with the pairwise alignment).

PMID- 16606687
TI  - Coupling modes and stoichiometry of Cl-/HCO3- exchange by slc26a3 and slc26a6.
AB  - The SLC26 transporters are a family of mostly luminal Cl- and HCO3- transporters.
      The transport mechanism and the Cl-/HCO3- stoichiometry are not known for any
      member of the family. To address these questions, we simultaneously measured the
      HCO3- and Cl- fluxes and the current or membrane potential of slc26a3 and slc26a6
      expressed in Xenopus laevis oocytes and the current of the transporters expressed
      in human embryonic kidney 293 cells. slc26a3 mediates a coupled 2Cl-/1HCO3-
      exchanger. The membrane potential modulated the apparent affinity for
      extracellular Cl- of Cl-/HCO3- exchange by slc26a3. Interestingly, the
      replacement of Cl- with NO3- or SCN- uncoupled the transport, with large NO3- and
      SCN- currents and low HCO3- transport. An apparent uncoupled current was also
      developed during the incubation of slc26a3-expressing oocytes in HCO3--buffered
      Cl--free media. These findings were used to develop a turnover cycle for Cl- and
      HCO3- transport by slc26a3. Cl- and HCO3- flux measurements revealed that slc26a6
      mediates a 1Cl-/2HCO3- exchange. Accordingly, holding the membrane potential at
      40 and -100 mV accelerated and inhibited, respectively, Cl--mediated HCO3-
      influx, and holding the membrane potential at -100 mV increased HCO3--mediated Cl
      influx. These findings indicate that slc26a6 functions as a coupled 1Cl-/2HCO3-
      exchanger. The significance of isoform-specific Cl- and HCO3- transport
      stoichiometry by slc26a3 and slc26a6 is discussed in the context of diseases of
      epithelial Cl- absorption and HCO3- secretion.

PMID- 16606688
TI  - Access of quaternary ammonium blockers to the internal pore of cyclic nucleotide
      gated channels: implications for the location of the gate.
AB  - Cyclic nucleotide-gated (CNG) channels play important roles in the transduction
      of visual and olfactory information by sensing changes in the intracellular
      concentration of cyclic nucleotides. We have investigated the interactions
      between intracellularly applied quaternary ammonium (QA) ions and the alpha
      subunit of rod cyclic nucleotide-gated channels. We have used a family of alkyl
      triethylammonium derivatives in which the length of one chain is altered. These
      QA derivatives blocked the permeation pathway of CNG channels in a concentration-
      and voltage-dependent manner. For QA compounds with tails longer than six
      methylene groups, increasing the length of the chain resulted in higher apparent
      affinities of approximately 1.2 RT per methylene group added, which is consistent
      with the presence of a hydrophobic pocket within the intracellular mouth of the
      channel that serves as part of the receptor binding site. At the single channel
      level, decyltriethyl ammonium (C10-TEA) ions did not change the unitary
      conductance but they did reduce the apparent mean open time, suggesting that the
      blocker binds to open channels. We provide four lines of evidence suggesting that
      QA ions can also bind to closed channels: (1) the extent of C10-TEA blockade at
      subsaturating [cGMP] was larger than at saturating agonist concentration, (2)
      under saturating concentrations of cGMP, cIMP, or cAMP, blockade levels were
      inversely correlated with the maximal probability of opening achieved by each
      agonist, (3) in the closed state, MTS reagents of comparable sizes to QA ions
      were able to modify V391C in the inner vestibule of the channel, and (4) in the
      closed state, C10-TEA was able to slow the Cd2+ inhibition observed in V391C
      channels. These results are in stark contrast to the well-established QA blockade
      mechanism in Kv channels, where these compounds can only access the inner
      vestibule in the open state because the gate that opens and closes the channel is
      located cytoplasmically with respect to the binding site of QA ions. Therefore,
      in the context of Kv channels, our observations suggest that the regions involved
      in opening and closing the permeation pathways in these two types of channels are
      different.

PMID- 16606689
TI  - The polyamine binding site in inward rectifier K+ channels.
AB  - Strongly inwardly rectifying potassium channels exhibit potent and steeply
      voltage-dependent block by intracellular polyamines. To locate the polyamine
      binding site, we have examined the effects of polyamine blockade on the rate of
      MTSEA modification of cysteine residues strategically substituted in the pore of
      a strongly rectifying Kir channel (Kir6.2[N160D]). Spermine only protected
      cysteines substituted at a deep location in the pore, between the "rectification
      controller" residue (N160D in Kir6.2, D172 in Kir2.1) and the selectivity filter,
      against MTSEA modification. In contrast, blockade with a longer synthetic
      polyamine (CGC-11179) also protected cysteines substituted at sites closer to the
      cytoplasmic entrance of the channel. Modification of a cysteine at the entrance
      to the inner cavity (169C) was unaffected by either spermine or CGC-11179, and
      spermine was clearly "locked" into the inner cavity (i.e., exhibited a
      dramatically slower exit rate) following modification of this residue. These data
      provide physical constraints on the spermine binding site, demonstrating that
      spermine stably binds at a deep site beyond the "rectification controller"
      residue, near the extracellular entrance to the channel.

PMID- 16606690
TI  - A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin
      remodeling.
AB  - Protein degradation, chromatin remodeling, and membrane trafficking are
      critically regulated by ubiquitylation. The presence of several coexisting
      ubiquitin-dependent processes, each of crucial importance to the cell, is
      remarkable. This brings up questions on how the usage of this versatile regulator
      is negotiated between the different cellular processes. During proteotoxic
      stress, the accumulation of ubiquitylated substrates coincides with the depletion
      of ubiquitylated histone H2A and chromatin remodeling. We show that this
      redistribution of ubiquitin during proteotoxic stress is a direct consequence of
      competition for the limited pool of free ubiquitin. Thus, the ubiquitin cycle
      couples various ubiquitin-dependent processes because of a rate-limiting pool of
      free ubiquitin. We propose that this ubiquitin equilibrium may allow cells to
      sense proteotoxic stress in a genome-wide fashion.

PMID- 16606691
TI  - Drosophila melanogaster Scramblases modulate synaptic transmission.
AB  - Scramblases are a family of single-pass plasma membrane proteins, identified by
      their purported ability to scramble phospholipids across the two layers of plasma
      membrane isolated from platelets and red blood cells. However, their true in vivo
      role has yet to be elucidated. We report the generation and isolation of null
      mutants of two Scramblases identified in Drosophila melanogaster. We demonstrate
      that flies lacking either or both of these Scramblases are not compromised in
      vivo in processes requiring scrambling of phospholipids. Instead, we show that D.
      melanogaster lacking both Scramblases have more vesicles and display enhanced
      recruitment from a reserve pool of vesicles and increased neurotransmitter
      secretion at the larval neuromuscular synapses. These defects are corrected by
      the introduction of a genomic copy of the Scramb 1 gene. The lack of phenotypes
      related to failure of scrambling and the neurophysiological analysis lead us to
      propose that Scramblases play a modulatory role in the process of
      neurotransmission.

PMID- 16606692
TI  - Lamina-associated polypeptide 2alpha regulates cell cycle progression and
      differentiation via the retinoblastoma-E2F pathway.
AB  - Lamina-associated polypeptide (LAP) 2alpha is a nonmembrane-bound LAP2 isoform
      that forms complexes with nucleoplasmic A-type lamins. In this study, we show
      that the overexpression of LAP2alpha in fibroblasts reduced proliferation and
      delayed entry into the cell cycle from a G0 arrest. In contrast, stable down
      regulation of LAP2alpha by RNA interference accelerated proliferation and
      interfered with cell cycle exit upon serum starvation. The LAP2alpha-linked cell
      cycle phenotype is mediated by the retinoblastoma (Rb) protein because the
      LAP2alpha COOH terminus directly bound Rb, and overexpressed LAP2alpha inhibited
      E2F/Rb-dependent reporter gene activity in G1 phase in an Rb-dependent manner.
      Furthermore, LAP2alpha associated with promoter sequences in endogenous E2F/Rb
      dependent target genes in vivo and negatively affected their expression. In
      addition, the expression of LAP2alpha in proliferating preadipocytes caused the
      accumulation of hypophosphorylated Rb, which is reminiscent of noncycling cells,
      and initiated partial differentiation into adipocytes. The effects of LAP2alpha
      on cell cycle progression and differentiation may be highly relevant for the cell
      and tissue-specific phenotypes observed in laminopathic diseases.

PMID- 16606694
TI  - Formation of a WIP-, WASp-, actin-, and myosin IIA-containing multiprotein
      complex in activated NK cells and its alteration by KIR inhibitory signaling.
AB  - The tumor natural killer (NK) cell line YTS was used to examine the cytoskeletal
      rearrangements required for cytolysis. A multiprotein complex weighing
      approximately 1.3 mD and consisting of WASp-interacting protein (WIP), Wiskott
      Aldrich syndrome protein (WASp), actin, and myosin IIA that formed during NK cell
      activation was identified. After induction of an inhibitory signal, the
      recruitment of actin and myosin IIA to a constitutive WIP-WASp complex was
      greatly decreased. Both actin and myosin IIA were recruited to WIP in the absence
      of WASp. This recruitment correlated with increased WIP phosphorylation, which
      was mediated by PKCtheta. Furthermore, the disruption of WIP expression by WIP
      RNA interference prevented the formation of this protein complex and led to
      almost complete inhibition of cytotoxic activity. Thus, the multiprotein complex
      is important for NK cell function, killer cell immunoglobulin-like receptor
      inhibitory signaling affects proteins involved in cytoskeletal rearrangements,
      and WIP plays a central role in the formation of the complex and in the
      regulation of NK cell activity.

PMID- 16606693
TI  - Internalization is required for proper Wingless signaling in Drosophila
      melanogaster.
AB  - The Wnt-Wingless (Wg) pathway regulates development through precisely controlled
      signaling. In this study, we show that intracellular trafficking regulates Wg
      signaling levels. In Drosophila melanogaster cells stimulated with Wg media,
      dynamin or Rab5 knockdown causes reduced Super8XTOPflash activity, suggesting
      that internalization and endosomal transport facilitate Wg signaling. In the
      wing, impaired dynamin function reduces Wg transcription. However, when Wg
      production is unaffected, extracellular Wg levels are increased. Despite this,
      target gene expression is reduced, indicating that internalization is also
      required for efficient Wg signaling in vivo. When endosomal transport is
      impaired, Wg signaling is similarly reduced. Conversely, the expression of Wg
      targets is enhanced by increased transport to endosomes or decreased hepatocyte
      growth factor-regulated tyrosine kinase substrate- mediated transport from
      endosomes. This increased signaling correlates with greater colocalized Wg,
      Arrow, and Dishevelled on endosomes. As these data indicate that endosomal
      transport promotes Wg signaling, our findings suggest that the regulation of
      endocytosis is a novel mechanism through which Wg signaling levels are
      determined.

PMID- 16606695
TI  - Cytotoxic T lymphocyte-induced killing in the absence of granzymes A and B is
      unique and distinct from both apoptosis and perforin-dependent lysis.
AB  - Cytotoxic T lymphocyte (CTL)-induced death triggered by the granule exocytosis
      pathway involves the perforin-dependent delivery of granzymes to the target cell.
      Gene targeting has shown that perforin is essential for this process; however,
      CTL deficient in the key granzymes A and B maintain the ability to kill their
      targets by granule exocytosis. It is not clear how granzyme AB(-/-) CTLs kill
      their targets, although it has been proposed that this occurs through perforin
      induced lysis. We found that purified granzyme B or CTLs from wild-type mice
      induced classic apoptotic cell death. Perforin-induced lysis was far more rapid
      and involved the formation of large plasma membrane protrusions. Cell death
      induced by granzyme AB(-/-) CTLs shared similar kinetics and morphological
      characteristics to apoptosis but followed a distinct series of molecular events.
      Therefore, CTLs from granzyme AB(-/-) mice induce target cell death by a unique
      mechanism that is distinct from both perforin lysis and apoptosis.

PMID- 16606696
TI  - Jodocus Lommius's Little Golden Book and the history of diagnostic semeiology.
AB  - This paper traces the nature and fortunes of Lommius' Medicinal Observations of
      1560, its relationship to ancient authors, its two-and-a-half centuries of fame,
      and its fall. Originating as an accessible manual of diagnosis for municipal
      authorities, it emphasized the observable aspects of illness and downplayed the
      role of humors and hidden causes. As a result, it both heralded and served the
      trend to symptom-based nosology. Eventually, as disease concepts shifted from
      symptoms to organs, Lommius was eclipsed by the next epistemic fashion:
      positivistic organicism. The multiple editions of this work invite us to
      reconsider the sustained influence of ancient writers, including Celsus, in
      medical pedagogy and semeiology, as well as the timing and location of the
      development of nosological concepts of disease. Class considerations and the
      proclivities of twentieth-century scholarship contributed to the obscurity of
      this book in our time.

PMID- 16606697
TI  - Integrated analysis of regulatory and metabolic networks reveals novel regulatory
      mechanisms in Saccharomyces cerevisiae.
AB  - We describe the use of model-driven analysis of multiple data types relevant to
      transcriptional regulation of metabolism to discover novel regulatory mechanisms
      in Saccharomyces cerevisiae. We have reconstructed the nutrient-controlled
      transcriptional regulatory network controlling metabolism in S. cerevisiae
      consisting of 55 transcription factors regulating 750 metabolic genes, based on
      information in the primary literature. This reconstructed regulatory network
      coupled with an existing genome-scale metabolic network model allows in silico
      prediction of growth phenotypes of regulatory gene deletions as well as gene
      expression profiles. We compared model predictions of gene expression changes in
      response to genetic and environmental perturbations to experimental data to
      identify potential novel targets for transcription factors. We then identified
      regulatory cascades connecting transcription factors to the potential targets
      through a systematic model expansion strategy using published genome-wide
      chromatin immunoprecipitation and binding-site-motif data sets. Finally, we show
      the ability of an integrated metabolic and regulatory network model to predict
      growth phenotypes of transcription factor knockout strains. These studies
      illustrate the potential of model-driven data integration to systematically
      discover novel components and interactions in regulatory and metabolic networks
      in eukaryotic cells.

PMID- 16606698
TI  - Conservation and functional significance of gene topology in the genome of
      Caenorhabditis elegans.
AB  - We have systematically examined the correlation between transcriptional
      expression pattern and the physical layout of gene pairs in the genome of
      Caenorhabditis elegans using a public tissue-specific SAGE library data set. We
      find a strong positive correlation in the expression patterns of neighboring gene
      pairs that are close together and transcribed in the same direction as well as
      for neighboring pairs that are located on opposing strands and transcribed in
      divergent directions. Coupling between members of nonoverlapping neighboring gene
      pairs is independent of operons and decreases to background levels as the
      distance increases beyond 10 kb. These findings suggest the existence of regional
      transcriptional domains in the C. elegans genome. In contrast, genes that are on
      opposing strands and transcribed in convergent directions are less
      transcriptionally coupled than the genome-wide background, suggesting a mutual
      inhibition mechanism. We have also examined the conservation and functional
      consequences of extreme cases of topological entanglement in the C. elegans
      genome, in which two or more genes physically overlap in their UTRs or coding
      regions. We have found that overlapping gene pairs are more conserved and are
      enriched in essential genes and genes that cause various defined phenotypes
      revealed by RNAi trials. SAGE analysis indicates that genes that are on the same
      strand, physically overlap, and transcript at the same directions are very highly
      correlated in gene expression, while overlapping gene pairs in which one member
      of the pair resides within an intron of the other are weakly, if at all, coupled,
      similar to convergent overlapping genes.

PMID- 16606699
TI  - Large-scale identification of protein-protein interaction of Escherichia coli K
      12.
AB  - Protein-protein interactions play key roles in protein function and the
      structural organization of a cell. A thorough description of these interactions
      should facilitate elucidation of cellular activities, targeted-drug design, and
      whole cell engineering. A large-scale comprehensive pull-down assay was performed
      using a His-tagged Escherichia coli ORF clone library. Of 4339 bait proteins
      tested, partners were found for 2667, including 779 of unknown function. Proteins
      copurifying with hexahistidine-tagged baits on a Ni2+-NTA column were identified
      by MALDI-TOF MS (matrix-assisted laser desorption ionization time of flight mass
      spectrometry). An extended analysis of these interacting networks by
      bioinformatics and experimentation should provide new insights and novel
      strategies for E. coli systems biology.

PMID- 16606700
TI  - Probing genomic diversity and evolution of Escherichia coli O157 by single
      nucleotide polymorphisms.
AB  - Infections by Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) are the
      predominant cause of bloody diarrhea and hemolytic uremic syndrome in the United
      States. In silico comparison of the two complete STEC O157 genomes (Sakai and
      EDL933) revealed a strikingly high level of sequence identity in orthologous
      protein-coding genes, limiting the use of nucleotide sequences to study the
      evolution and epidemiology of this bacterial pathogen. To systematically examine
      single nucleotide polymorphisms (SNPs) at a genome scale, we designed comparative
      genome sequencing microarrays and analyzed 1199 chromosomal genes (a total of
      1,167,948 bp) and 92,721 bp of the large virulence plasmid (pO157) of eleven
      outbreak-associated STEC O157 strains. We discovered 906 SNPs in 523 chromosomal
      genes and observed a high level of DNA polymorphisms among the pO157 plasmids.
      Based on a uniform rate of synonymous substitution for Escherichia coli and
      Salmonella enterica (4.7x10(-9) per site per year), we estimate that the most
      recent common ancestor of the contemporary beta-glucuronidase-negative, non
      sorbitolfermenting STEC O157 strains existed ca. 40 thousand years ago. The
      phylogeny of the STEC O157 strains based on the informative synonymous SNPs was
      compared to the maximum parsimony trees inferred from pulsed-field gel
      electrophoresis and multilocus variable numbers of tandem repeats analysis. The
      topological discrepancies indicate that, in contrast to the synonymous mutations,
      parts of STEC O157 genomes have evolved through different mechanisms with highly
      variable divergence rates. The SNP loci reported here will provide useful genetic
      markers for developing high-throughput methods for fine-resolution genotyping of
      STEC O157. Functional characterization of nucleotide polymorphisms should shed
      new insights on the evolution, epidemiology, and pathogenesis of STEC O157 and
      related pathogens.

PMID- 16606701
TI  - Haplotype variation in structure and expression of a gene cluster associated with
      a quantitative trait locus for improved yield in rice.
AB  - By constructing nearly isogenic lines (NILs) that differ only at a single
      quantitative trait locus (QTL), we fine-mapped the yield-improving QTL qGY2-1 to
      a 102.9-kb region on rice chromosome 2. Comparison analysis of the genomic
      sequences in the mapped QTL region between the donor (Dongxiang wild rice, Oryza
      rufipogon Griff.) and recurrent (Guichao2, Oryza sativa ssp. indica) parents used
      for the development of NILs identified the haplotypes of a leucine-rich repeat
      receptor kinase gene cluster, which showed extensive allelic variation. The
      sequences between genes in the cluster had a very high rate of divergence. More
      importantly, the genes themselves also differed between two haplotypes: Only 92%
      identity was observed for one allele, and another allele was found to have
      completely lost its allelic counterpart in Guichao2. The other six shared genes
      all showed >98% identity, and four of these exhibited obvious regulatory
      variation. The same haplotype segments also differed in length (43.9-kb in
      Guichao2 vs. 52.6-kb in Dongxiang wild rice). Such extensive sequence variation
      was also observed between orthologous regions of indica (cv. 93-11) and japonica
      (cv. Nipponbare) subspecies of Oryza sativa. Different rates of sequence
      divergence within the cluster have resulted in haplotype variability in 13 rice
      accessions. We also detected allelic expression variation in this gene cluster,
      in which some genes gave unequal expression of alleles in hybrids. These allelic
      variations in structure and expression suggest that the leucine-rich repeat
      receptor kinase gene cluster identified in our study should be a particularly
      good candidate for the source of the yield QTL.

PMID- 16606702
TI  - A comprehensive catalog of human KRAB-associated zinc finger genes: insights into
      the evolutionary history of a large family of transcriptional repressors.
AB  - Kruppel-type zinc finger (ZNF) motifs are prevalent components of transcription
      factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor
      domain is attached to a tandem array of DNA-binding zinc-finger motifs, are
      specific to tetrapod vertebrates and represent the largest class of ZNF proteins
      in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched
      the genome sequence for key motifs and then constructed and manually curated gene
      models incorporating those sequences. The resulting gene catalog contains 423
      KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether
      predict at least 742 structurally distinct proteins. Active rounds of segmental
      duplication, involving single genes or larger regions and including both tandem
      and distributed duplication events, have driven the expansion of this mammalian
      gene family. Comparisons between the human genes and ZNF loci mined from the
      draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes
      that are conserved in mammals but also highlighted a substantial level of lineage
      specific change; at least 136 KRAB-ZNF coding genes are primate specific,
      including many recent duplicates. KRAB-ZNF genes are widely expressed and
      clustered genes are typically not coregulated, indicating that paralogs have
      evolved to fill roles in many different biological processes. To facilitate
      further study, we have developed a Web-based public resource with access to gene
      models, sequences, and other data, including visualization tools to provide
      genomic context and interaction with other public data sets.

PMID- 16606703
TI  - Evolutionary expansion and divergence in the ZNF91 subfamily of primate-specific
      zinc finger genes.
AB  - Most genes are conserved in mammals, but certain gene families have acquired
      large numbers of lineage-specific loci through repeated rounds of gene
      duplication, divergence, and loss that have continued in each mammalian group.
      One such family encodes KRAB-zinc finger (KRAB-ZNF) proteins, which function as
      transcriptional repressors. One particular subfamily of KRAB-ZNF genes, including
      ZNF91, has expanded specifically in primates to comprise more than 110 loci in
      the human genome. Genes of the ZNF91 subfamily reside in large gene clusters near
      centromeric regions of human chromosomes 19 and 7 with smaller clusters or
      isolated copies in other locations. Phylogenetic analysis indicates that many of
      these genes arose before the split between the New and Old World monkeys, but the
      ZNF91 subfamily has continued to expand and diversify throughout the evolution of
      apes and humans. Paralogous loci are distinguished by divergence within their
      zinc finger arrays, indicating selection for proteins with different regulatory
      targets. In addition, many loci produce multiple alternatively spliced
      transcripts encoding proteins that may serve separate and perhaps even opposing
      regulatory roles because of the modular motif structure of KRAB-ZNF genes. The
      tissue-specific expression patterns and rapid structural divergence of ZNF91
      subfamily genes suggest a role in determining gene expression differences between
      species and the evolution of novel primate traits.

PMID- 16606705
TI  - Unbiased location analysis of E2F1-binding sites suggests a widespread role for
      E2F1 in the human genome.
AB  - The E2F family of transcription factors regulates basic cellular processes. Here,
      we take an unbiased approach towards identifying E2F1 target genes by examining
      localization of E2F1-binding sites using high-density oligonucleotide tiling
      arrays. To begin, we developed a statistically-based methodology for analysis of
      ChIP-chip data obtained from arrays that represent 30 Mb of the human genome.
      Using this methodology, we identified regions bound by E2F1, MYC, and RNA
      Polymerase II (POLR2A). We found a large number of binding sites for all three
      factors; extrapolation suggests there may be approximately 20,000-30,000 E2F1-
      and MYC-binding sites and approximately 12,000-17,000 active promoters in HeLa
      cells. In contrast to our results for MYC, we find that the majority of E2F1
      binding sites (>80%) are located in core promoters and that 50% of the sites
      overlap transcription starts. Only a small fraction of E2F1 sites possess the
      canonical binding motif. Surprisingly, we found that approximately 30% of genes
      in the 30-Mb region possessed an E2F1 binding site in a core promoter and E2F1
      was bound near to 83% of POLR2A-bound sites. To determine if these results were
      representative of the entire human genome, we performed ChIP-chip analyses of
      approximately 24,000 promoters and confirmed that greater than 20% of the
      promoters were bound by E2F1. Our results suggest that E2F1 is recruited to
      promoters via a method distinct from recognition of the known consensus site and
      point toward a new understanding of E2F1 as a factor that contributes to the
      regulation of a large fraction of human genes.

PMID- 16606704
TI  - Genome-wide computational prediction of transcriptional regulatory modules
      reveals new insights into human gene expression.
AB  - The identification of regulatory regions is one of the most important and
      challenging problems toward the functional annotation of the human genome. In
      higher eukaryotes, transcription-factor (TF) binding sites are often organized in
      clusters called cis-regulatory modules (CRM). While the prediction of individual
      TF-binding sites is a notoriously difficult problem, CRM prediction has proven to
      be somewhat more reliable. Starting from a set of predicted binding sites for
      more than 200 TF families documented in Transfac, we describe an algorithm
      relying on the principle that CRMs generally contain several phylogenetically
      conserved binding sites for a few different TFs. The method allows the prediction
      of more than 118,000 CRMs within the human genome. A subset of these is shown to
      be bound in vivo by TFs using ChIP-chip. Their analysis reveals, among other
      things, that CRM density varies widely across the genome, with CRM-rich regions
      often being located near genes encoding transcription factors involved in
      development. Predicted CRMs show a surprising enrichment near the 3' end of genes
      and in regions far from genes. We document the tendency for certain TFs to bind
      modules located in specific regions with respect to their target genes and
      identify TFs likely to be involved in tissue-specific regulation. The set of
      predicted CRMs, which is made available as a public database called PReMod
      (http://genomequebec.mcgill.ca/PReMod), will help analyze regulatory mechanisms
      in specific biological systems.

PMID- 16606706
TI  - A preliminary comparative analysis of primate segmental duplications shows
      elevated substitution rates and a great-ape expansion of intrachromosomal
      duplications.
AB  - Compared with other sequenced animal genomes, human segmental duplications appear
      larger, more interspersed, and disproportionately represented as high-sequence
      identity alignments. Global sequence divergence estimates of human duplications
      have suggested an expansion relatively recently during hominoid evolution. Based
      on primate comparative sequence analysis of 37 unique duplication-transition
      regions, we establish a molecular clock for their divergence that shows a
      significant increase in their effective substitution rate when compared with
      unique genomic sequence. Fluorescent in situ hybridization (FISH) analyses from
      1053 random nonhuman primate BACs indicate that great-ape species have been
      enriched for interspersed segmental duplications compared with representative Old
      World and New World monkeys. These findings support computational analyses that
      show a 12-fold excess of recent (>98%) intrachromosomal duplications when
      compared with duplications between nonhomologous chromosomes. These architectural
      shifts in genomic structure and elevated substitution rates have important
      implications for the emergence of new genes, gene-expression differences, and
      structural variation among humans and great apes.

PMID- 16606708
TI  - ADSA Foundation Scholar Award: Implementing waste solutions for dairy and
      livestock farms.
AB  - Water quality in the United States is threatened by contamination with nutrients,
      primarily nitrogen (N) and phosphorus (P). Animal manure can be a valuable
      resource for farmers, providing nutrients, improving soil structure, and
      increasing vegetative cover to reduce erosion potential. At the same time,
      application of manure nutrients in excess of crop requirements can result in
      environmental contamination. Concentrated animal agriculture has been identified
      as a significant source of nutrient contamination of surface water, nitrogen
      contamination of groundwater, and ammonia emission. Areas facing the dilemma of
      an economically important livestock industry concentrated in an environmentally
      sensitive area have few options. If agricultural practices continue as they have
      in the past, despite the significant changes in agricultural intensity and
      changing environmental conditions, continued damage to water resources and a loss
      of fishing and recreational activity are inevitable. If agricultural productivity
      is reduced, however, the maintenance of a stable farm economy, a viable rural
      economy, and a reliable domestic food supply are seriously threatened. The
      identification and implementation of solutions to the generation of excess manure
      in confined animal feeding operations are necessary to enable such agricultural
      operations to thrive in environmentally sensitive areas such as the Chesapeake
      Bay Watershed. This paper will review an innovative collaborative approach to the
      development of a manure and litter solutions strategy by a diverse array of
      potential problem-solvers.

PMID- 16606709
TI  - Use of chitosan for selective removal of beta-lactoglobulin from whey.
AB  - A method is described for selective removal of undenatured beta-lactoglobulin
      from cheese whey based on interactions between whey proteins and chitosan. Whey
      was previously clarified at pH 4.5 with addition of chitosan (25 mg/100 mL), and
      selective removal of beta-lactoglobulin was studied in the pH interval 4.6 to
      6.5. Addition of chitosan caused selective precipitation of beta-lactoglobulin
      that increased with pH. The content of beta-lactoglobulin in whey decreased as
      the amount of chitosan added was increased. At pH 6.2, addition of 1.9 to 3.0
      mg/mL of chitosan led to complete removal of beta-lactoglobulin, whereas at least
      80% of the rest of whey proteins remained in solution. The production of cheese
      whey without beta-lactoglobulin could help to expand the applications of dairy by
      products in food processing, and to isolate hypoallergenic whey protein
      concentrates.

PMID- 16606710
TI  - Effects of a Lactobacillus casei synbiotic on serum lipoprotein, intestinal
      microflora, and organic acids in rats.
AB  - The main aim of this study was to evaluate the effectiveness of 3 synbiotic
      diets: 1) containing Lactobacillus casei ASCC 292 and fructooligosaccharides (LF
      diet); 2) containing L. casei ASCC 292 and maltodextrin (LM diet); and 3)
      containing L. casei ASCC 292, fructooligosaccharide, and maltodextrin (LFM diet)
      to reduce serum cholesterol in male Wistar rats. The effect of the synbiotic
      diets on intestinal microflora, concentration of organic acids, and the
      possibility of translocation of lactobacilli were also investigated. The LFM diet
      lowered serum total cholesterol and triglyceride levels, whereas the LM diet
      increased serum high-density lipoprotein cholesterol level. However, synbiotic
      diets did not contribute to a change in low-density lipoprotein cholesterol level
      compared with the control diet. There was a decrease in the population of
      staphylococci, bacteroides, Escherichia coli, and total coliforms in most bowel
      regions with the LFM diet compared with the control (which did not contain any
      synbiotic). In general, the LFM diet contributed to a higher concentration of
      lactic acid that may have contributed to the decrease in the population of
      pathogenic microorganisms compared with the control. Fructooligosaccharide was
      the preferred substrate for production of acetic acid. Results from this study
      showed that the synbiotic diet that contained L. casei ASCC 292,
      fructooligosaccharide, and maltodextrin beneficially altered cholesterol levels
      and produced a healthier bowel microbial population without translocation of
      lactobacilli to other organs.

PMID- 16606711
TI  - Increasing the protein content of ice cream.
AB  - Vanilla ice cream was made with a mix composition of 10.5% milk fat, 10.5% milk
      SNF, 12% beet sugar, and 4% corn syrup solids. None of the batches made contained
      stabilizer or emulsifier. The control (treatment 1) contained 3.78% protein.
      Treatments 2 and 5 contained 30% more protein, treatments 3 and 6 contained 60%
      more protein, and treatments 4 and 7 contained 90% more protein compared with
      treatment 1 by addition of whey protein concentrate or milk protein concentrate
      powders, respectively. In all treatments, levels of milk fat, milk SNF, beet
      sugar, and corn syrup solids were kept constant at 37% total solids. Mix protein
      content for treatment 1 was 3.78%, treatment 2 was 4.90%, treatment 5 was 4.91%,
      treatments 3 and 6 were 6.05%, and treatments 4 and 7 were 7.18%. This
      represented a 29.89, 60.05, 89.95, 29.63, 60.05, and 89.95% increase in protein
      for treatment 2 through treatment 7 compared with treatment 1, respectively. Milk
      protein level influenced ice crystal size; with increased protein, the ice
      crystal size was favorably reduced in treatments 2, 4, and 5 and was similar in
      treatments 3, 6, and 7 compared with treatment 1. At 1 wk postmanufacture,
      overall texture acceptance for all treatments was more desirable compared with
      treatment 1. When evaluating all parameters, treatment 2 with added whey protein
      concentrate and treatments 5 and 6 with added milk protein concentrate were
      similar or improved compared with treatment 1. It is possible to produce
      acceptable ice cream with higher levels of protein.

PMID- 16606712
TI  - Rapid determination of Swiss cheese composition by Fourier transform
      infrared/attenuated total reflectance spectroscopy.
AB  - There is a need for rapid and simple techniques that can be used to predict the
      quality of cheese. The aim of this research was to develop a simple and rapid
      screening tool for monitoring Swiss cheese composition by using Fourier transform
      infrared spectroscopy. Twenty Swiss cheese samples from different manufacturers
      and degree of maturity were evaluated. Direct measurements of Swiss cheese slices
      (approximately 0.5 g) were made using a MIRacle 3-reflection diamond attenuated
      total reflectance (ATR) accessory. Reference methods for moisture (vacuum oven),
      protein content (Kjeldahl), and fat (Babcock) were used. Calibration models were
      developed based on a cross-validated (leave-one-out approach) partial least
      squares regression. The information-rich infrared spectral range for Swiss cheese
      samples was from 3,000 to 2,800 cm(-1) and 1,800 to 900 cm(-1). The performance
      statistics for cross-validated models gave estimates for standard error of cross
      validation of 0.45, 0.25, and 0.21% for moisture, protein, and fat respectively,
      and correlation coefficients r > 0.96. Furthermore, the ATR infrared protocol
      allowed for the classification of cheeses according to manufacturer and aging
      based on unique spectral information, especially of carbonyl groups, probably due
      to their distinctive lipid composition. Attenuated total reflectance infrared
      spectroscopy allowed for the rapid (approximately 3-min analysis time) and
      accurate analysis of the composition of Swiss cheese. This technique could
      contribute to the development of simple and rapid protocols for monitoring
      complex biochemical changes, and predicting the final quality of the cheese.

PMID- 16606713
TI  - A survey of extractable persistent organochlorine pollutants in Chinese
      commercial yogurt.
AB  - Eighteen Chinese commercial brands of yogurt were collected from supermarkets
      from December 2002 to April 2003, for characterization of organochlorine
      pesticides (OCP) and polychlorinated biphenyls (PCB). Besides monitoring OCP and
      PCB by gas chromatography, the levels of extractable persistent organochlorine
      (EPOCl; i.e., sulfuric acid-resistant EPOCl) were also determined by instrumental
      neutron activation analysis. The results indicated that the contamination pattern
      of the selected OCP and PCB were in the order of dichlorodiphenyltrichloroethanes
      (DDT) approximately hexachlorocyclohexanes (HCH) >> aldrin > or = chlordanes > or
      = heptachlor epoxide and 4-6 chlorinated biphenyls (CB) >> 7-10 CB, respectively.
      Furthermore, beta-HCH, and 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene were
      the predominant isomers of HCH and DDT residues in yogurt, and PCB with 4,4'- and
      2,3,5- substitution patterns were the predominant congeners of PCB residues.
      Also, the results indicated that the mean level of total chlorine in the
      identified organochlorine species was below 4% of EPOCl in yogurt, which implied
      that more than 96% of EPOCl measured in yogurt samples could not be accounted for
      by selected OCP and PCB.

PMID- 16606714
TI  - Interaction of brine concentration, brine temperature, and presalting on salt
      penetration in Ragusano cheese.
AB  - Thirty-one 3.6-kg blocks of Ragusano cheese were made on each of 6 different days
      (in different weeks) starting with a different batch of milk on each day. On d 1,
      3, and 5, the cheeses were not presalted and on d 2, 4, and 6, all cheeses were
      presalted (PS). One of the 31 blocks of cheese was selected at random for
      analysis before brine salting (i.e., on d 0). The remaining 30 blocks were
      randomly divided into 2 groups of 15 blocks each; one group was placed in 18%
      brine (18%B) and the other group was placed in saturated brine (SB). For the 15
      blocks within each of the 2 brine concentrations (BC), 5 blocks were placed in a
      brine tank at 12 degrees C, 5 at 15 degrees C, and 5 at 18 degrees C, and
      submerged for 24 d. The research objective was to determine the combined impacts
      (i.e., interactions) of PS the curd before stretching, BC (SB vs. 18%B), and
      brine temperature (BT; 12, 15, and 18 degrees C) on salt uptake, moisture
      content, and yield of Ragusano cheese. Although BC, BT, and PS each had their own
      separate impacts on salt uptake, there was little interaction of these effects on
      salt uptake when they were used in combination. The PS most quickly delivered
      salt to the interior of the cheese and was the most effective approach to salting
      for controlling early gas formation. There were strong separate impacts of BC,
      BT, and PS on cheese moisture content, moisture loss, and net weight loss, with
      BC having the largest separate impact on these parameters. Reducing BT reduced
      salt content and increased moisture, but the effects were small. The more
      important effect of reduced BT was to reduce growth of gas forming bacteria. The
      18%B produced higher moisture, and less moisture and weight loss than SB. The
      effect of interactions of BC, BT, and PS on moisture loss and net weight loss
      were small. To achieve the maximum benefit from the various approaches to salting
      for controlling early gas formation in Ragusano cheese, PS combined with slightly
      lower BT (i.e., 15 degrees C instead of 18 degrees C) should be used. Although
      using 18%B instead of SB did increase salt uptake, the point at which improved
      salt uptake occurred due to use of 18%B did not provide benefit in prevention of
      early gas formation, as reported separately. However, use of 18%B instead of SB
      provided a 9.98% increase in cheese yield due to reduced moisture loss during
      brining; this would be very attractive to cheese makers. The increase in yield
      needs to be balanced against the risk of growth of undesirable bacteria in the
      18%B and the creation of another cheese quality defect.

PMID- 16606715
TI  - Probiotic cheese production using Lactobacillus casei cells immobilized on fruit
      pieces.
AB  - Lactobacillus casei cells were immobilized on fruit (apple and pear) pieces and
      the immobilized biocatalysts were used separately as adjuncts in probiotic cheese
      making. In parallel, cheese with free L. casei cells and cheese only from
      renneted milk were prepared. The produced cheeses were ripened at 4 to 6 degrees
      C and the effect of salting and ripening time on lactose, lactic acid, ethanol
      concentration, pH, and lactic acid bacteria viable counts were investigated. Fat,
      protein, and moisture contents were in the range of usual levels of commercial
      cheeses. Reactivation in whey of L. casei cells immobilized on fruit pieces after
      7 mo of ripening showed a higher rate of pH decrease and lower final pH value
      compared with reactivation of samples withdrawn from the remaining mass of the
      cheese without fruit pieces, from cheese with free L. casei, and rennet cheese.
      Preliminary sensory evaluation revealed the fruity taste of the cheeses
      containing immobilized L. casei cells on fruit pieces. Commercial Feta cheese was
      characterized by a more sour taste, whereas no significant differences concerning
      cheese flavor were reported by the panel between cheese containing free L. casei
      and rennet cheese. Salted cheeses scored similar values to commercial Feta
      cheese, whereas unsalted cheese scores were significantly lower, but still
      acceptable to the sensory panelists.

PMID- 16606716
TI  - Nonstarter lactic acid bacteria biofilms and calcium lactate crystals in Cheddar
      cheese.
AB  - A sanitized cheese plant was swabbed for the presence of nonstarter lactic acid
      bacteria (NSLAB) biofilms. Swabs were analyzed to determine the sources and
      microorganisms responsible for contamination. In pilot plant experiments, cheese
      vats filled with standard cheese milk (lactose:protein = 1.47) and ultrafiltered
      cheese milk (lactose:protein = 1.23) were inoculated with Lactococcus lactis ssp.
      cremoris starter culture (8 log cfu/mL) with or without Lactobacillus curvatus or
      Pediococci acidilactici as adjunct cultures (2 log cfu/mL). Cheddar cheeses were
      aged at 7.2 or 10 degrees C for 168 d. The raw milk silo, ultrafiltration unit,
      cheddaring belt, and cheese tower had NSLAB biofilms ranging from 2 to 4 log
      cfu/100 cm2. The population of Lb. curvatus reached 8 log cfu/g, whereas P.
      acidilactici reached 7 log cfu/g of experimental Cheddar cheese in 14 d. Higher
      NSLAB counts were observed in the first 14 d of aging in cheese stored at 10
      degrees C compared with that stored at 7.2 degrees C. However, microbial counts
      decreased more quickly in Cheddar cheeses aged at 10 degrees C compared with 7.2
      degrees C after 28 d. In cheeses without specific adjunct cultures (Lb. curvatus
      or P. acidilactici), calcium lactate crystals were not observed within 168 d.
      However, crystals were observed after only 56 d in cheeses containing Lb.
      curvatus, which also had increased concentration of D(-)-lactic acid compared
      with control cheeses. Our research shows that low levels of contamination with
      certain NSLAB can result in calcium lactate crystals, regardless of
      lactose:protein ratio.

PMID- 16606717
TI  - Leptin does not act directly on mammary epithelial cells in prepubertal dairy
      heifers.
AB  - The mammary gland of prepubertal dairy heifers consists of parenchyma expanding
      into the stroma, a matrix of connective and adipose tissue. High planes of
      nutrition increase stromal mass, but inhibit growth of parenchyma. The parenchyma
      consists of epithelial cells proliferating in response to growth factors such as
      insulin like growth factor-I (IGF-I). These observations have led to the
      hypothesis that elevated planes of nutrition increase leptin production, which in
      turn inhibits IGF-I-mediated epithelial cell proliferation. To assess this
      possibility, heifers were offered planes of nutrition sustaining average daily
      gains of 715 g/d (normal; NP) or 1,202 g/d (high; HP) from 42 d of age until
      slaughter at 240 kg. At slaughter, HP heifers had 2-fold greater plasma leptin
      concentration and 3-fold greater leptin mRNA abundance in mammary stroma and
      parenchyma. To assess the causal nature between leptin and parenchymal
      development, the induction of signaling events and functional responses in the
      MAC-T cell line and in primary mammary epithelial cells by leptin was examined.
      Leptin did not induce phosphorylation of signal transducers and activators of
      transcription (STAT)3, STAT5, extracellular signal-regulated kinase (ERK1/2), or
      AKT/Protein kinase B. Consistent with its inability to signal, leptin did not
      alter basal- or IGF-I-stimulated thymidine incorporation or increase suppressors
      of cytokine signaling 3 (SOCS3) expression in these cells. Transcripts
      corresponding to the short leptin receptor form were present in mammary tissue,
      but those corresponding to the long signaling form were not detected in either
      mammary tissue or cells. In conclusion, elevated planes of nutrition increase
      leptin synthesis in mammary stroma, but leptin does not act directly on bovine
      mammary epithelial cells.

PMID- 16606718
TI  - Effect of milking frequency and diet on milk production, energy balance, and
      reproduction in dairy cows.
AB  - The objective of this study was to determine the effects of reduced milking
      frequency and increased dietary energy density in early lactation on milk
      production, energy balance, and subsequent fertility. Sixty-six spring-calving,
      multiparous Holstein-Friesian cows were assigned to 1 of 3 treatment groups: once
      daily milking on a standard diet (1xST); 3-times daily milking on a standard diet
      (3xST); and 3-times daily milking on a high-energy diet. Treatments were imposed
      for the first 28 d of lactation, after which all groups were milked twice daily
      and fed the standard diet. During the treatment period, the 1xST cows had 19.6%
      lower milk yield and higher milk fat and milk protein concentrations (15.7 and
      10.2%, respectively) compared with 3xST. Dry matter (DM) intake was similar
      between 1xST and 3xST during the treatment period (12.64 vs. 13.25 kg/ d; SED =
      0.82). Daily energy balance was less negative for 1xST compared with 3xST during
      wk 1 to 3 of lactation [-3.92 vs. -5.30 unite fourragere lait (UFL)/d; SED =
      0.65; 1 UFL is equal to the net energy for lactation of 1 kg of standard air-dry
      barley]. During the treatment period, the cows on the high-energy diet had 17%
      higher milk yield, higher DM intake (15.5 vs. 13.9 kg/d; SED = 0.71), and similar
      energy balance (-4.45 vs. -4.35 UFL/d; SED = 0.65) compared to 3xST. Diet had no
      significant effect on any of the fertility variables measured. The interval to
      first ovulation was shorter for 1xST than 3xST (18.3d vs. 28.6d; SED = 1.76). In
      conclusion, once-daily milking in early lactation may promote earlier resumption
      of ovarian cyclicity, mediated through improved nutritional status.

PMID- 16606719
TI  - Acute phase proteins in bovine milk in an experimental model of Staphylococcus
      aureus subclinical mastitis.
AB  - The objectives were to establish the origin of 2 acute phase proteins in milk
      during subclinical bovine mastitis and to characterize the relationship between
      those proteins in milk and blood. Haptoglobin (Hp) and mammary-associated serum
      amyloid A (M-SAA3) appear in milk during mastitis, whereas Hp and serum amyloid A
      increase in serum during mastitis. The concentrations of these proteins were
      determined in an experimental model using a field strain of Staphylococcus aureus
      to induce subclinical mastitis in dairy cows. The expression of mRNA coding for
      these proteins was assessed and the presence of M-SAA3 in mammary tissues was
      determined using immunocytochemistry. Increases of M-SAA3 and Hp in milk occurred
      within 12 h of Staphylococcus aureus infusion, with peak concentrations occurring
      3 d after infusion of the bacteria. The increase of acute phase proteins in milk
      (15 h) preceded the increase in serum concentrations of both proteins (24 h).
      Expression of mRNA for M-SAA3 and Hp increased in both mammary and hepatic
      tissues 48 h after infusion of the mammary glands. In mammary tissue, the
      increase of M-SAA3 mRNA was greater than the increase in Hp mRNA expression,
      whereas in hepatic tissue, the increase in M-SAA3 mRNA was less than that for Hp
      mRNA. Immunocytochemistry demonstrated that M-SAA3 protein was present within
      secretory epithelial cells at significantly higher levels in infected mammary
      glands than in control tissues. These proteins, which have host defense and
      antibacterial activities, may play a significant role in the early response to
      invasion of mammary tissues by pathogenic bacteria.

PMID- 16606720
TI  - Comparison of two strategies for systemic antibiotic treatment of dairy cows with
      retained fetal membranes: preventive vs. selective treatment.
AB  - The objective of this study was to evaluate the efficacy of a blanket systemic
      preventive treatment (PT) of cows having retained fetal membranes (RFM) with 1
      mg/kg of ceftiofur administered the first day after calving regardless of their
      body temperature. This strategy was compared with a selective treatment (ST)
      strategy in which only cows having RFM and a rectal temperature > or = 39.5
      degrees C within 10 d postpartum received ceftiofur. Cows that retained their
      fetal membranes for at least 24 h after calving were allocated to 2 groups.
      Rectal temperature was measured daily for 10 d postpartum. Sixty PT cows having
      RFM received a daily ceftiofur (1 mg/kg of body weight) treatment, administered
      subcutaneously during the first 3 d after diagnosis of RFM. If rectal temperature
      was > or = 39.5 degrees C after 3 daily treatments, cows received ceftiofur for 2
      more days. Therapy in 53 ST cows was based on selective administration of
      ceftiofur to cows having fever during the first 10 d postpartum. Treatment was
      conducted for 3 to 5 consecutive days as described for PT cows, beginning on the
      first day of fever. In both groups, manual removal of the placenta was not
      attempted and antibiotic drugs were not administered into the uterus. For every
      cow having RFM enrolled in PT or ST, 1 cow without RFM that had calved on the
      same day was enrolled in a healthy control group (n = 113). All cows received two
      25-mg doses of PGF(2alpha): 1 dose between 18 and 24 d and 1 dose between 32 and
      38 d postpartum. The PT did not reduce the proportion of cows experiencing fever
      during 10 d postpartum compared with ST cows (71.7 vs. 69.8%). Results were
      compared using logistic regression models and survival analyses. The artificial
      insemination submission rate between 42 and 62 d postpartum was greater in PT
      (41.2 vs. 20.8 vs. 24.5%), but total conception rate was less in ST and control
      cows, respectively (25.0 vs. 38.9 vs. 36.2%). In this trial, a preventive
      systemic antibiotic treatment of all cows having RFM was not superior to a
      selective antibiotic treatment of cows only in case of fever.

PMID- 16606721
TI  - Risk factors for reduced locomotion in dairy cattle on nineteen farms in The
      Netherlands.
AB  - A 3-point locomotion scoring system was used that incorporated the position of
      the back of cows while standing and when walking to investigate risk factors for
      elevated locomotion scores of 1,450 dairy cows on 19 farms in The Netherlands.
      Each of the farms was visited twice in an 18-mo period from February 2003 to July
      2004. At each visit, all milking and dry cows were scored for locomotion by a
      single observer. Two multivariable regression models were constructed to identify
      factors associated with elevated mean locomotion score (increased abnormality)
      and the percentage of cows with the highest score (score 3). Risk factors for
      increased locomotion score were having a hoof-trimming stall with foot-lifting
      apparatus compared with not having such apparatus (increase in locomotion score =
      0.15), presence of a footbath at the parlor exit or other site compared with not
      having a footbath on the farm (increase in locomotion score = 0.17 and 0.19,
      respectively), not providing supplemental vitamins and minerals to lactating cows
      compared with supplementing animals (increase in locomotion score = 0.17) and
      feeding corn silage to heifers compared with not doing so (increase in locomotion
      score = 0.10). The results provide a framework for hypotheses for future
      investigations of risk factors for high locomotion scores.

PMID- 16606723
TI  - A conjugated linoleic acid supplement containing trans-10, cis-12 reduces milk
      fat synthesis in lactating sheep.
AB  - The efficacy of conjugated linoleic acid (CLA) supplements containing trans-10,
      cis-12 for reducing milk fat synthesis has been well documented in dairy cows,
      but studies with other ruminant species are less convincing, and there have been
      no investigations of this in sheep. Therefore, the current study was designed to
      determine whether trans-10, cis-12 CLA would inhibit milk fat synthesis in sheep.
      Twenty multiparous ewes in early lactation were paired and randomly allocated to
      2 treatments: grass hay plus concentrate either unsupplemented (control) or
      supplemented with lipid-encapsulated CLA to provide 2.4 g/d of trans-10, cis-12
      CLA. The CLA dose was based on published responses of dairy cows extrapolated to
      ewes on a metabolic body weight basis. The experimental design was a 2-period
      crossover with 10-d treatment periods separated by a 10-d interval. Compared with
      the control, CLA supplementation reduced milk fat content from 6.4 to 4.9% and
      reduced fat yield from 95 to 80 g/d. The CLA treatment also increased milk yield
      from 1,471 to 1,611 g/d and increased protein yield from 68 to 73 g/d. Milk
      protein content and DMI were unaffected by treatment. The reduction in milk fat
      yield was due to decreases in both de novo fatty acid synthesis and uptake of
      preformed fatty acids. Milk fat content of trans-10, cis-12 CLA was < 0.01 and
      0.12 g/100 g of fatty acids for the control and CLA treatments, respectively. The
      transfer efficiency of trans-10, cis-12 CLA from the dietary supplement into milk
      fat was 3.8%. Results of the present study demonstrate that a CLA supplement
      containing trans-10, cis-12 CLA reduces milk fat synthesis in lactating sheep in
      a manner similar to dairy cows when fed at an equivalent dose (metabolic body
      weight basis). Furthermore, the nutrients spared by the reduction in milk fat
      coincided with an increase in milk and milk protein yield.

PMID- 16606722
TI  - Endoscopic examination and tissue sampling of the bovine teat and udder cistern.
AB  - The aim of this study was to evaluate the application of an endoscopic technique
      to investigate the teat and udder cisterns of the bovine mammary gland, and to
      biopsy tissues within the cisterns. An anesthetic protocol for application in
      standing animals was designed, using a combination of general and local
      anesthesia. Individual quarter milk production (QMP), quarter somatic cell count
      (SCC), and occurrence of new intramammary infection were assessed after
      application of the technique, and possible applications for biopsies collected
      were investigated. Bovine teat and gland cistern lining could be visualized and
      small biopsy samples could be collected. The collected biopsy samples were
      successfully used in histological-histopathological examination and PCR analysis.
      To study the impact of endoscopy on QMP, milk SCC, and bacteriology, endoscopic
      examination of 12 low SCC (<200,000 cells/ mL) quarters was performed in 8
      different first- and second-lactation cows. Immediately following endoscopy, 8
      quarters received antibiotic treatment, whereas 4 quarters remained untreated.
      During a 15-d follow-up, no new intramammary infection could be observed in the
      endoscopically treated quarters. For QMP, no significant interaction between time
      and treatment could be observed throughout the 15-d follow-up period. Quarter SCC
      did not differ among treatments (control, endoscopy with antibiotics, and
      endoscopy without antibiotics). In conclusion, the endoscopic technique is
      suitable for examination and tissue biopsy collection of the bovine mammary gland
      cisterns without major interference with QMP and quarter SCC.

PMID- 16606724
TI  - Prevention of fatty liver in transition dairy cows by subcutaneous injections of
      glucagon.
AB  - The main objective of this study was to test the extent to which injecting
      glucagon subcutaneously for 14 d beginning at d 2 postpartum would prevent fatty
      liver development in transition dairy cows. Twenty-four multiparous Holstein cows
      were fed 6 kg of cracked corn in addition to their standard diet during the last
      30 d of a dry period to induce postpartum development of fatty liver. Glucagon at
      either 7.5 or 15 mg/d or saline (control) was injected subcutaneously 3 times
      daily for 14 d beginning at d 2 postpartum. Glucagon at 15 mg/ d prevented liver
      triacylglycerol accumulation in postpartum dairy cows. Glucagon at 7.5 mg/d
      showed potential for fatty liver prevention. Glucagon increased concentration of
      plasma glucose and insulin and decreased plasma nonesterified fatty acid
      concentrations. No effects of glucagon were detected on plasma beta
      hydroxybutyrate concentrations. Glucagon affected neither feed intake nor milk
      production. Moreover, milk composition was not altered by glucagon. Milk urea N
      concentrations decreased, and plasma urea N concentrations tended to decrease
      during glucagon administration, indicating that glucagon may improve protein use.
      Liver glycogen concentrations were not affected by glucagon. No significant
      differences in body condition scores were detected among treatments throughout
      the study. These results indicate that subcutaneous glucagon injections can
      prevent fatty liver in transition dairy cows without causing major production and
      metabolite disturbances.

PMID- 16606725
TI  - Evaluation of net energy expenditures of dairy cows according to body weight
      changes over a full lactation.
AB  - Equations that predict daily dry matter intake (DMI) of a lactating cow could be
      evaluated by comparing the predicted accumulation of energy in body weight (BW)
      over the course of lactation with the observed BW evolution. However, to do so
      requires that first the energy balance calculations from observed DMI are
      evaluated. The purpose of the work reported here was to determine the degree of
      deviation of predicted from observed BW, according to net energy for lactation
      (NE(L)) balance calculated from weekly observations of DMI, BW, and fat-corrected
      milk production in 21 sets of full-lactation data, and to determine an
      appropriate correction of the NE(L) bias for subsequent DMI prediction
      evaluations. When the National Research Council maintenance equation 0.08 x
      BW(kg)(0.75) was used in energy balance calculation, BW was overpredicted with an
      increasing difference between the cumulative predicted BW and observed BW as
      lactation progressed. Placing all the error of BW prediction into maintenance
      energy expenditures resulted in a best-fit equation of 0.096 +/- 0.003 Mcal/kg of
      BW(0.75). A time-dependent equation was also developed, in which weekly
      maintenance expenditures were determined as the NE(L) expenditure to yield a zero
      NE(L) balance and could be described by a second-order polynomial equation
      related to week of lactation (WOL) where maintenance NE(L) = [-0.0227(+/- 0.0098)
      x WOL2 + 1.352(+/- 0.456) x WOL + 78.09(+/- 4.92) Mcal/kg of BW(0.75)] x 10(-3).
      Average maintenance energy expenditure at the onset of lactation was
      approximately 0.08 Mcal/kg of BW(0.75), and this value increased to a plateau at
      wk 15 of lactation of approximately 0.098 Mcal/kg of BW(0.75). Standard
      deviations between data sets of weekly maintenance parameter estimates throughout
      lactation were large but consistent at approximately 25% of the mean. Revision of
      the maintenance energy expenditure estimate substantially improved BW prediction
      by the energy balance model. On average, the 0.096 Mcal of NE(L)/kg of BW(0.75)
      equation resulted in the best BW predictions, although substantial variation
      existed around this value.

PMID- 16606726
TI  - Prediction of dry matter intake throughout lactation in a dynamic model of dairy
      cow performance.
AB  - In the dynamic modeling of dairy cow performance over a full lactation, the
      difference between net energy intake and net energy used for maintenance, growth,
      and output in milk accumulates in body reserves. A simple dynamic model of net
      energy balance was constructed to select, out of some common dry matter intake
      (DMI) prediction equations, the one that resulted in a minimum cumulative bias in
      body energy deposition. Dry matter intake was predicted using the Cornell Net
      Carbohydrate and Protein System, Agricultural Research Council, or National
      Research Council (NRC) DMI equations from body weight (BW) and predicted fat
      corrected milk yield. The instantaneous BW of cows at progressive weeks of
      lactation was simulated as the numerical integral of the BW change obtained from
      the predicted net energy balance. Predicted DMI and BW from each DMI equation,
      using either of 2 equations to describe maintenance energy expenditures, were
      compared statistically against observed data from 21 herd average published full
      lactation data sets. All DMI equations underpredicted BW and DMI, but the NRC DMI
      equation resulted in the minimum cumulative error in predicted BW and DMI. As a
      general solution to prevent predicted BW from deviating substantially over time
      from the observed BW, a lipostatic feedback mechanism was integrated into the NRC
      DMI equation as a 2-parameter linear function of the relative size of simulated
      body reserves and week of lactation. Residual sum of squares was reduced on
      average by 52% for BW predictions and by 41% for DMI predictions by inclusion of
      the negative feedback with parameters taken from the average of all 21 least
      squares fits. Similarly, root mean square prediction error (%) was reduced by 30%
      on average for BW predictions and by 23% for DMI predictions. Inclusion of a
      feedback of energy reserves onto predicted DMI, simulating lipostatic regulation
      of BW, solved the problem of final BW deviation within a dynamic model and
      improved its DMI prediction to a satisfactory level.

PMID- 16606727
TI  - NutriDense corn grain and corn silage for dairy cows.
AB  - Twenty multiparous Holstein cows, 4 of them surgically fitted with ruminal
      cannulas, were used in a replicated 4 x 4 Latin square to compare the effects of
      whole-plant silage and grain produced from NutriDense (ND), leafy NutriDense
      (LND), or a conventional yellow dent (YD) hybrid on ruminal fermentation, total
      tract nutrient digestibility, and performance of lactating dairy cows. On a DM
      basis, diets contained 30.6% corn silage and 27.7% corn grain provided from the 3
      hybrids according to the following combinations: 1) YD grain and YD silage, 2) YD
      grain and LND silage, 3) ND grain and YD silage, and 4) ND grain and LND silage.
      The average concentrations of crude protein, neutral and acid detergent fiber,
      and ether extract of LND silage and ND grain were higher, but the contents of
      nonfibrous carbohydrates and starch were lower than those of their YD
      counterparts. Although DM intake was similar among treatments, feeding ND grain,
      LND silage, or both reduced the intakes of nonfibrous carbohydrates and starch
      but increased the intake of ether extract. Apparent digestibility of starch in
      the total tract was highest for the diet that contained LND silage and YD grain,
      whereas the amount and percentage of ether extract that were apparently digested
      in the total tract was increased and tended to be increased, respectively, by the
      addition of ND grain, LND silage, or both to the diets. Ruminal fermentation
      parameters were unaffected by treatments except for the concentration of ammonia
      nitrogen in the ruminal fluid, which tended to be increased by the feeding of ND
      grain, LND silage, or both. Production of milk, crude and true protein, fat,
      lactose, and total solids did not differ among diets. Concentration of milk urea
      nitrogen increased when the ND grain, LND silage, or both were fed to the cows.
      Results indicate that ND grain and LND silage were similar to the conventional
      grain and silage for the feeding of lactating dairy cows.

PMID- 16606728
TI  - Effect of total mixed ration composition on fermentation and efficiency of
      ruminal microbial crude protein synthesis in vitro.
AB  - The goal of this study was to identify dietary factors that affect fermentation
      and efficiency of microbial crude protein (CP(M)) synthesis in the rumen in
      vitro. We used 16 total mixed, dairy cow rations with known digestibilities that
      varied in ingredient composition and nutrient content. Each ration was incubated
      in a Rusitec (n = 3) for 15 d, and fermentation of different fractions was
      assessed. Observed extents of fermentation in 24 h were 35 to 47% for organic
      matter, 25 to 60% for crude protein, 3 to 28% for neutral detergent fiber, and 31
      to 45% for gross energy. Organic matter fermentation depended on the content of
      crude protein and neutral detergent fiber in the ration. We studied net synthesis
      of CP(M) using an 15N dilution technique and found that 7 d of continuous 15N
      application are needed to achieve an 15N enrichment plateau in the N of isolated
      microbes in this type of study. The efficiency of CP(M) synthesis was 141 to 286
      g/kg of fermented organic matter or 4.9 to 11.1 g/MJ of metabolizable energy, and
      these ranges agree with those found in the literature. Multiple regressions to
      predict the efficiency of CP(M) synthesis by diet data showed that crude protein
      was the only dietary chemical fraction that had a significant effect. Fat content
      and the inclusion rate of corn silage in the ration also tended to improve
      efficiency. We suggest that microbial need for preformed amino acids may explain
      the crude protein effect. A large part of the variation in efficiency of
      microbial activity still remains unexplained.

PMID- 16606729
TI  - Effect of total mixed ration composition on amino acid profiles of different
      fractions of ruminal microbes in vitro.
AB  - The objective was to study the variation in the amino acid profile of microbial
      fractions obtained after feeding 16 total mixed rations for dairy cows in a
      Rusitec. Each ration was incubated for 15 d in 3-fold replicate. The rations
      showed high variation in the inclusion level of different ingredients and the
      content of proximal nutrients, fiber fractions, and energy. Three microbial
      fractions were isolated by centrifugation. The reference microbes (RM) were
      isolated from the liquid effluent of vessels between d 7 and 15 of incubation.
      Solid-associated microbes (SAM) were detached with methylcellulose from feed
      residues after incubation, and liquid-associated microbes (LAM) were obtained
      from the liquid content of the vessel. Both SAM and LAM were obtained only once
      for each vessel at the end of the incubation period. Across all rations,
      significant differences were found between RM, LAM, and SAM in amino acid
      concentration for some, but not all, amino acids. Within each microbial fraction,
      significant differences in the content of amino acids were found between rations.
      Multiple linear regression analysis did not show that the content of a certain
      nutrient or the inclusion rate of single feedstuffs could be used to predict the
      amino acid profile of microbial protein with an adequate level of accuracy.
      Further studies are necessary before the supply of individual microbial amino
      acids to the cows' duodenum can be modeled and predicted in dependence of diet
      data.

PMID- 16606730
TI  - Variation of milk citrate with stage of lactation and de novo fatty acid
      synthesis in dairy cows.
AB  - Citrate is a normal constituent of milk that affects milk-processing
      characteristics. It is an intermediate in the tricarboxylic acid cycle and plays
      an indirect role in fat synthesis by providing reducing equivalents in the form
      of NADPH. The objective of this study was to investigate variation in citrate
      with stage of lactation and de novo fatty acid synthesis, without confounding
      dietary effects. Twenty-four cows were fed the same diet, and milk citrate and
      fatty acids were determined over a 10-d period. Eight cows were in early
      lactation [13 +/- 1.8 d in milk (DIM; mean +/-standard error], 8 in midlactation
      (130 +/-4.6 DIM), and 8 in late lactation (283 +/-3.4 DIM). For cows in early,
      mid, and late lactation, milk yield was 34.4, 34.4, and 21.4 L/d [standard error
      of difference (SED) 1.78]; milk fat was 50.4, 40.3, and 41.4 g/L (3.68); milk
      citrate was 11.3, 9.7, and 10.1 mmol/L (0.64); the ratio of 4-14 C:18-20 C fatty
      acids was 0.9, 1.3, and 1.2 (0.07). Activity of the fatty acid synthase enzyme
      system (EC 2.3.1.85) was calculated as acetate used for chain elongation (ACE);
      ACE (mol/d) for cows in early, mid, and late lactation, was 7.3, 11.1, and 8.1
      (SED 1.05). For individual cows, citrate (mmol/L) = 14.3 -0.44 xACE (r2 = 0.58).
      We propose that ACE provides a more accurate indication of synthase activity than
      do fatty acid ratios or yields. This study confirms the hypothesis that variation
      in milk citrate with stage of lactation is related to de novo synthesis of fatty
      acids and that the relationship is independent of diet and milk yield.

PMID- 16606731
TI  - Effects of methionine and lysine on fermentation in vitro and in vivo, nutrient
      flow to the intestine, and milk production.
AB  - Three experiments were conducted to investigate the feasibility of using
      crystalline methionine and lysine as protein supplements for lactating Holstein
      cows. In the first experiment, Met (dl-methionine) and Lys (l-lysine-HCl) were
      added to diets used in continuous culture bioreactors to estimate optimal
      concentrations for use in subsequent in vivo experiments. The second experiment
      measured ruminal fermentation and nutrient flow to the small intestine when Met
      and Lys were top-dressed on diets fed to nonlactating cows. The third experiment
      measured lactation performance when Met and Lys were added to diets fed to late
      lactation cows. Providing 0.29 and 2.27% of dry matter as Met and Lys,
      respectively, provided the largest improvement in fermentation in vitro and these
      concentrations were used in subsequent experiments. When Met and Lys were top
      dressed on diets fed to nonlactating cows, no changes in total tract N digestion
      were observed. No changes in microbial protein production or ruminal fermentation
      were observed. Adding Met and Lys did not change production or efficiency of
      production of milk or milk components by late lactation cows. These data indicate
      that providing supplemental Met and Lys during late lactation does not
      significantly improve the protein status of the cow and therefore may not improve
      milk production.

PMID- 16606732
TI  - Effect of ruminally protected methionine on splanchnic metabolism of amino acids
      in lactating dairy cows.
AB  - The effect of ruminally protected Met (RPM) on splanchnic metabolism was measured
      in 3 primiparous and 3 multiparous Holstein cows. Doses of RPM (0, 36, and 72
      g/d) were tested in a replicated 3 x 3 Latin square design, over 3 consecutive 14
      d experimental periods. A mixed ration was fed in 12 equal meals per d (average
      dry matter intake: 17.5 +/- 0.08 kg/d). Indwelling catheters were surgically
      implanted in the mesenteric artery and the portal and hepatic veins for blood
      collection, as well as in 2 distal branches of the mesenteric vein for infusion
      of p-aminohippurate to determine blood flow. On d 14 of each period, a temporary
      catheter was inserted into a mammary vein and 6 hourly blood samples were
      collected to determine plasma concentrations of metabolites, hormones, and their
      respective fluxes across the splanchnic bed and mammary glands. Yields of milk
      (32.8, 32.0, and 32.9 +/- 0.92 kg/d) and protein (1,028, 1,053, and 1,075 +/-
      28.7 g/d) were unaffected by level of RPM. However, the true protein content in
      milk from primiparous cows increased linearly (2.92, 3.09, and 3.34 +/- 0.077%).
      The addition of RPM linearly increased the net flux of Met across the portal
      drained viscera, which resulted in increased arterial Met concentrations (25, 29,
      and 40 +/- 1.1 microM). Although it had no significant effect on net portal and
      hepatic fluxes of other essential amino acids, RPM resulted in a linear increase
      in the total splanchnic output of Ile, Leu, Phe, and Thr. These results suggest
      that feeding RPM triggered a homeostatic response resulting in less utilization
      of certain essential amino acids through the gastrointestinal tract and liver.
      Net mammary uptake of Met did not change with the addition of RPM. However,
      mammary extraction of Met decreased in a linear fashion in response to increased
      arterial inflow.

PMID- 16606733
TI  - Effect of amount and ruminal degradability of soybean meal protein on performance
      of lactating dairy cows.
AB  - Twenty-eight Holstein cows (4 with ruminal cannulas) were blocked by days in milk
      into 7 groups and then randomly assigned to 1 of 7 balanced 4 x 4 Latin square
      diet sequences. The diets contained [dry matter (DM) basis] 20% alfalfa silage,
      35% corn silage, and 45% concentrate mainly from high-moisture corn and soybean
      meal. Diets differed in crude protein (CP) content and source of protein
      supplement: diet A) 15.6% CP, 3.7% solvent-extracted soybean meal (SSBM), 4.5%
      expeller soybean meal (ESBM); diet B) 16.6% CP, 9.6% SSBM, 0% ESBM; diet C) 16.6%
      CP, 4.6% SSBM, 5.9% ESBM; and diet D) 17.6% CP, 11.7% SSBM, 0% ESBM. Each
      experimental period consisted of 14 d for adaptation plus 14 d for collection of
      production data. Sampling of ruminal digesta and spot sampling of blood, feces,
      and urine was done on d 26 and 27 of each period. Planned contrasts compared
      included diet A vs. diet B, diet B vs. diet C, and diet B vs. diet D. There were
      no effects of diet on most of the production traits measured. However, milk yield
      tended to be higher for diet B vs. A. Trends were also detected for higher DM
      intake and weight gain and lower milk yield/DM intake in cows fed diet D vs. diet
      B. Milk lactose content was higher on diets A and C than on B. Ruminal NH3 was
      higher on diet D vs. B, but other ruminal metabolites, apparent nutrient
      digestibility, and estimated bacterial CP synthesis did not differ across diets.
      Blood and milk urea-N were higher on diets C and D than on B; milk urea-N was
      higher on diet B than on A. Increasing dietary CP from 16.6% (diet B) to 17.6%
      (diet D) increased urinary N excretion by 54 g/d and reduced apparent N
      efficiency (milk N/N intake) by 2.5 percentage units, without altering yield.
      Under the conditions of this trial, milk production was not improved by feeding
      rumen-undegraded protein from ESBM or greater amounts of rumen-degraded protein
      from SSBM. Feeding more than 16.6% CP depressed N efficiency.

PMID- 16606734
TI  - Effect of corn silage hybrid and metabolizable protein supply on nitrogen
      metabolism of lactating dairy cows.
AB  - This experiment was conducted to determine the effects of corn silage hybrid and
      supply of metabolizable protein (MP) on manure excretion and N metabolism by
      lactating dairy cows. Eight Holstein cows in midlactation (replicated 4 x 4 Latin
      square with 21-d periods) were fed 1 of 4 treatments, arranged factorially. Diets
      contained 55% corn silage made from a dual-purpose hybrid or a brown midrib (BMR)
      hybrid, and 45% concentrate that contained either a low or high concentration of
      rumen undegradable protein (altered by the addition of fish meal and treated
      soybean meal). Crude protein averaged 14.0 and 17.5% and supply of MP averaged
      2,360 and 2,990 g/d for the low and high MP treatments (not affected by hybrid).
      Increasing supply of MP greatly increased urine output and tended to increase
      total manure output, whereas diets with BMR silage tended to reduce manure
      output. Increased MP supply increased daily excretion of manure N by 25% (465 vs.
      374 g/d), fecal N by 27 g, and urinary N by 64 g. When the effect of N intake was
      removed, cows fed BMR silage excreted about 15 g/d less N via manure than cows
      fed the other silage. Rumen ammonia, volatile fatty acid concentrations, and pH
      were not affected by treatment. Dry matter intake (overall mean = 24.9 kg/d)
      tended to be increased with increased MP but was not affected by hybrid. Milk
      production for cows fed BMR was higher than for cows fed the dual-purpose hybrid
      (36.9 vs. 35.3 kg/d), but because of changes in fat concentration, yield of
      energy-corrected milk was not affected by treatment. The only interaction
      observed was increased yield of milk protein when BMR silage was combined with
      increased supply of MP.

PMID- 16606735
TI  - Developmental changes in the kinetics of glucose and urea in Holstein calves.
AB  - Because weaning is the point when the nutrient composition of feed changes for
      the neonatal ruminant, the present experiment was conducted to assess the
      developmental changes in the kinetics of glucose and urea over this period, using
      stable isotopes of glucose and urea, at 4, 13, and 24 wk in calves. Plasma
      concentrations of nonesterified fatty acids, amino-N, urea-N, and insulin-like
      growth factor-I increased, but that of growth hormone decreased with age. The
      plasma glucose concentration increased at 13 wk of age and thereafter decreased
      at 24 wk of age. The glucose irreversible loss and recycling rates were
      significantly higher at 4 wk of age than at 13 and 24 wk of age. On the other
      hand, the irreversible loss and recycling rates of urea, as well as the urea pool
      size, were higher at 24 wk of age than at 4 and 13 wk. It is concluded that
      weaning at 6 wk is the pivotal time for the alteration of glucose kinetics.
      However, the aging process, but not weaning, is important for changes in the
      kinetics of urea in calves.

PMID- 16606736
TI  - Modeling small-scale dairy farms in central Mexico using multi-criteria
      programming.
AB  - Milk supply from Mexican dairy farms does not meet demand and small-scale farms
      can contribute toward closing the gap. Two multi-criteria programming techniques,
      goal programming and compromise programming, were used in a study of small-scale
      dairy farms in central Mexico. To build the goal and compromise programming
      models, 4 ordinary linear programming models were also developed, which had
      objective functions to maximize metabolizable energy for milk production, to
      maximize margin of income over feed costs, to maximize metabolizable protein for
      milk production, and to minimize purchased feedstuffs. Neither multi-criteria
      approach was significantly better than the other; however, by applying both
      models it was possible to perform a more comprehensive analysis of these small
      scale dairy systems. The multi-criteria programming models affirm findings from
      previous work and suggest that a forage strategy based on alfalfa, ryegrass, and
      corn silage would meet nutrient requirements of the herd. Both models suggested
      that there is an economic advantage in rescheduling the calving season to the
      second and third calendar quarters to better synchronize higher demand for
      nutrients with the period of high forage availability.

PMID- 16606737
TI  - Short communication: Canola meal as a substitute for cottonseed meal in diet of
      midlactation Holsteins.
AB  - The growing demand by humans for monounsaturated vegetable oils has provided
      canola meal (CM) for use in dairy diets because it possesses an excellent
      nitrogen profile for rumen microbes. Six midlactation cows were used in a
      replicated 3 x 3 Latin square design with 3 periods of 20 d each. Treatments
      included diets with 1) CM, 2) 50% CM + 50% cottonseed meal (CSM), and 3) CSM.
      Total crude protein (CP), nonprotein nitrogen, and rapidly degradable true
      protein (% of CP) were greater in CM than in CSM. The neutral and acid detergent
      fibers, slowly degradable true protein, and unavailable CP were lower in CM than
      in CSM. Daily feeding of 3.4 kg of CM instead of 5.6 kg of CSM enhanced milk
      percentage of protein and SNF, and improved total tract digestibility of dry
      matter and CP. Therefore, CM offers an economical substitute for CSM in
      midlactation diets when commercial access, cost, and quality of CSM are variable.

PMID- 16606738
TI  - Effects of replacing grass silage with barley silage in dairy cow diets.
AB  - This study examined the effects of gradually replacing grass silage with whole
      crop barley silage on feed intake, ruminal and total tract digestibility, and
      milk yield in lactating dairy cows. Four dairy cows in early lactation, equipped
      with rumen cannulas, were fed 4 diets over four 21-d periods. The diets consisted
      of 4 forage mixtures of grass silage and whole-crop barley silage supplemented
      with 8.9 kg/d of concentrates [dry matter (DM) basis]. The proportion of barley
      silage in the forage was adjusted to 0, 0.20, 0.40, and 0.60 kg/ kg of DM.
      Ruminal nutrient metabolism was measured on the basis of digesta flow entering
      the omasal canal. Ammonia concentrations and volatile fatty acid profiles were
      determined in the rumen fluid. Ruminal digestion and passage kinetics were
      assessed by the rumen evacuation technique. Replacement of grass silage with
      barley silage had no effect on DM, digestible organic matter, or neutral
      detergent fiber (NDF) intake, but starch intake increased, whereas nitrogen and
      digestible NDF (dNDF) intake decreased. Increases in the proportion of barley
      silage linearly decreased milk yield, and the molar proportion of acetate in the
      rumen, and increased that of propionate, butyrate, and valerate. Decreases in
      milk yield due to inclusion of barley silage were attributed to decreases in diet
      digestibility and nutrient supply to the animal. Barley silage linearly decreased
      organic matter digestibility in the total tract and NDF and dNDF digestibility in
      the rumen and the total tract, and decreased nonammonia N flow entering the
      omasal canal. No significant differences between diets were noted in the
      digestion rate of dNDF or passage rate of indigestible NDF from the rumen.
      Decreases in organic matter and NDF digestibility were attributed to the higher
      indigestible NDF concentration of barley silage compared with that of grass
      silage and to the smaller pool size of dNDF in the rumen.

PMID- 16606739
TI  - Supplementation of 1% L-glutamine to milk replacer does not overcome the growth
      depression in calves caused by soy protein concentrate.
AB  - Glutamine, an important fuel and biosynthetic precursor in intestinal epithelial
      cells, helps maintain intestinal integrity and function when supplemented to the
      diet of many species. The hypothesis tested here was that glutamine
      supplementation would overcome the decreased average daily gain (ADG) and altered
      intestinal morphology caused by milk replacer containing soy protein concentrate
      (SPC). Holstein calves (9 male and 1 freemartin female per treatment) were
      assigned to diets of 1) all-milk-protein (from whey proteins) milk replacer, 2)
      milk replacer with 60% milk protein replacement from SPC, and 3) SPC milk
      replacer as in diet 2 plus 1% (dry basis) l-glutamine. Milk replacers were
      reconstituted to 12.5% solids and were fed at 10% of body weight from d 3 to 10
      of age, and at 12% of body weight (adjusted weekly) from d 10 through 4 wk of
      age. No dry feed (starter) was fed, but water was freely available. Glutamine was
      added at each feeding to reconstituted milk replacer. Five calves from each
      treatment were slaughtered at the end of wk 4 for measurements of intestinal
      morphology. The ADG was greater for calves fed the all-milk control than for
      those fed SPC; glutamine did not improve ADG (0.344, 0.281, and 0.282 kg/d for
      diets 1 to 3, respectively). Intake of protein was adequate for all groups and
      did not explain the lower growth for calves fed SPC. Villus height and crypt
      depth did not differ among treatments in the duodenum. In the jejunum, villus
      height (713, 506, and 464 mum, for diets 1 to 3, respectively) and crypt depth
      (300, 209, and 229 mum, respectively) were greater for calves fed all milk
      protein than for either SPC group. In the ileum, villus height was greater for
      calves fed all milk than for either soy group (532, 458, and 456 mum), whereas
      crypt depth tended to be greater (352, 301, and 383 mum for diets 1 to 3,
      respectively), and the villus to crypt ratio was lower for calves supplemented
      with glutamine than for those fed SPC alone. Urea N concentration in plasma was
      greater for calves supplemented with glutamine than for those fed SPC alone,
      indicating that glutamine was at least partially catabolized. Supplemental l
      glutamine did not improve growth or intestinal morphology of calves fed milk
      replacer containing SPC.

PMID- 16606740
TI  - Effect of dietary crude protein concentration on ruminal nitrogen metabolism in
      lactating dairy cows.
AB  - Ten lactating Holstein cows fitted with ruminal cannulas that were part of a
      larger feeding trial were blocked by days in milk into 2 groups and then randomly
      assigned to 1 of 2 incomplete 5 x 5 Latin squares. Diets contained [dry matter
      (DM) basis] 25% alfalfa silage, 25% corn silage, and 50% concentrate. Rolled high
      moisture shelled corn was replaced with solvent-extracted soybean meal to
      increase crude protein (CP) from 13.5% to 15.0, 16.5, 17.9, and 19.4% of DM. Each
      of the 4 experimental periods lasted 28 d with data and sample collection
      performed during the last 8 d. Digesta samples were collected from the omasum to
      quantify the ruminal outflow of different N fractions. Intake of DM was not
      affected but showed a quadratic trend with maxima of 23.9 kg/d at 16.5% CP.
      Ruminal outflow of total bacterial nonammonia N (NAN) was not different among
      diets but a significant linear effect of dietary CP was detected for this
      variable. Bacterial efficiency (g of total bacterial NAN flow/kg of organic
      matter truly digested in the rumen) and omasal flows of dietary NAN and total NAN
      also showed positive linear responses to dietary CP. Total NAN flow increased
      from 574 g/d at 13.5% CP to 688 g/d at 16.5% CP but did not increase further with
      the feeding of more CP. Under the conditions of this study, 16.5% of dietary CP
      appeared to be sufficient for maximal ruminal outflow of total bacterial NAN and
      total NAN.

PMID- 16606741
TI  - Effect of dietary crude protein concentration on milk production and nitrogen
      utilization in lactating dairy cows.
AB  - Forty lactating Holstein cows, including 10 with ruminal cannulas, were blocked
      by days in milk into 8 groups and then randomly assigned to 1 of 8 incomplete 5 x
      5 Latin squares to assess the effects of 5 levels of dietary crude protein (CP)
      on milk production and N use. Diets contained 25% alfalfa silage, 25% corn
      silage, and 50% concentrate, on a dry matter (DM) basis. Rolled high-moisture
      shelled corn was replaced with solvent-extracted soybean meal to increase CP from
      13.5 to 15.0, 16.5, 17.9, and 19.4% of DM. Each of the 4 experimental periods
      lasted 28 d, with 14 d for adaptation and 14 d for data collection. Spot sampling
      of ruminal digesta, blood, urine, and feces was conducted on d 21 of each period.
      Intake of DM was not affected by diet but milk fat content as well as ruminal
      acetate, NH3, and branched-chain volatile fatty acids, urinary allantoin, and
      blood and milk urea all increased linearly with increasing CP. Milk and protein
      yield showed trends for quadratic responses to dietary CP and were, respectively,
      38.3 and 1.18 kg/d at 16.5% CP. As a proportion of N intake, urinary N excretion
      increased from 23.8 to 36.2%, whereas N secreted in milk decreased from 36.5 to
      25.4%, as dietary protein increased from 13.5 to 19.4%. Under the conditions of
      this study, yield of milk and protein were not increased by feeding more than
      16.5% CP. The linear increase in urinary N excretion resulted from a sharp
      decline in N efficiency as dietary CP content increased.

PMID- 16606742
TI  - Dry period length to maximize production across adjacent lactations and lifetime
      production.
AB  - The primary objectives of this research were to determine the dry period lengths
      that maximize production across adjacent lactations and also dry period length
      that maximizes lifetime yield. Effect of days dry (DD) after lactations 1 through
      3 were determined separately for both adjacent lactation sums and lifetime yield.
      Field data, collected through the Dairy Herd Improvement Association, on US
      Holstein cows first calving between January 1997 and January 2004 were utilized.
      Lifetime records were restricted to cows first calving no later than December
      1999. Actual lactation yields, in contrast to standardized records, were used to
      calculate lactation sums and lifetime records. Herds were required to be on test
      for the entire period to avoid partial records. Another important edit was that
      actual calving dates had to agree with expected calving dates, based on reported
      days open, within 10 d. This edit ensured that the producer knew, at least at one
      point in time, when the cow was going to calve. Cow effects were corrected for in
      both the adjacent lactation and lifetime analyses. The minimum DD to maximize
      production across adjacent lactations depended on parity. For yield across first
      and second lactations, there was little loss in production with a minimum of 40
      to 45 DD. Longer dry periods (55 to 65 DD) were required after second and third
      lactations however, presumably due to the lower persistency of second and later
      lactation cows. Lifetime production was maximized by 40 to 50 DD after first
      lactation and 30 to 40 DD after second and later lactations. Fewer DD were
      required to maximize lifetime yield than adjacent lactation yield because cows
      with fewer DD also had more lifetime days in milk. Although dry periods of 30 to
      40 d can be used after second and later lactations without cost in lifetime
      yield, their benefit to lifetime production is minimal. Dry periods shorter than
      30 d or longer than 70 d are costly to lifetime yield and should be avoided. Dry
      periods longer than 80 d are even more costly than dry periods less than 30 d.

PMID- 16606743
TI  - Short communication: Comparison of protocols to estimate twenty-four-hour fat and
      protein percentages for herds with a robotic milking system.
AB  - Currently, different protocols are used in various countries to estimate the 24-h
      fat and protein percentages for dairy cows that are milked with an automatic
      milking system. These protocols include estimating 24-h fat and protein
      percentages from 1) single samples from all animals in the herd; 2) single
      samples of fat adjusted for covariates and single samples of protein unadjusted
      for covariates; or 3) all samples (adjusted and unadjusted) collected on test
      days where test days vary in length from 10 to 18 h. The accuracy of estimated
      component percentages in predicting observed percentages was determined via
      agreement analysis for four protocols. Analysis of the data suggests collecting
      all samples (unadjusted for covariates) during a sampling period of at least 16 h
      on test day to be the most accurate protocol when estimating 24-h fat and protein
      percentages in herds with automatic milking systems.

PMID- 16606744
TI  - Benefits of cooperation between breeding programs in the presence of genotype by
      environment interaction.
AB  - Dairy cattle breeding programs and dairy farmers are selecting sires and dams
      across environments. Genotype x environment interaction (G x E) limits the
      possibilities for cooperation between breeding programs operating in different
      environments. The objectives of this study were 2-fold: 1) to investigate the
      effects of heritability, selection intensity, number of progeny per bull, and
      size of breeding programs on possibilities for cooperation between dairy cattle
      breeding programs in the short and long term in the presence of G x E, and 2) to
      quantify the effect of such cooperation on genetic gain. A dairy cattle situation
      with 2 breeding programs operating in 2 environments was simulated using a
      deterministic pseudo-BLUP selection index model. Long-term cooperation between
      the 2 breeding programs was possible in the presence of G x E, when the genetic
      correlation was higher than 0.80 to 0.90, resulting in up to 15% extra genetic
      gain. In addition, in the initial generations of selection, the breeding programs
      could benefit from mutually selecting sires and dams from each other when the
      genetic correlation was as low as 0.40 to 0.60. With more intense selection,
      breeding programs were less likely to benefit from cooperation with breeding
      programs in other environments. Heritability and number of progeny per bull had
      little effect on possibilities for cooperation, unless the heritabilities and the
      number of progeny per bull were extremely different in the 2 environments. Small
      breeding programs benefited more from cooperation than did large breeding
      programs, and benefits were possible even at lower values (i.e., <0.80) of the
      genetic correlation. Possibilities for cooperation across environments would
      affect the optimal design of dairy cattle breeding programs considering genetic
      gain, inbreeding, and costs.

PMID- 16606745
TI  - Optimization of dairy cattle breeding programs for different environments with
      genotype by environment interaction.
AB  - Dairy cattle breeding organizations tend to sell semen to breeders operating in
      different environments and genotype x environment interaction may play a role.
      The objective of this study was to investigate optimization of dairy cattle
      breeding programs for 2 environments with genotype x environment interaction.
      Breeding strategies differed in 1) including 1 or 2 environments in the breeding
      goal, 2) running either 1 or 2 breeding programs, and 3) progeny testing bulls in
      1 or 2 environments. Breeding strategies were evaluated on average genetic gain
      of both environments, which was predicted by using a pseudo-BLUP selection index
      model. When both environments were equally important and the genetic correlation
      was higher than 0.61, the highest average genetic gain was achieved with a single
      breeding program with progeny-testing all bulls in both environments. When the
      genetic correlation was lower than 0.61, it was optimal to have 2 environment
      specific breeding programs progeny-testing an equal number of bulls in their own
      environment only. Breeding strategies differed by 2 to 12% in average genetic
      gain, when the genetic correlation ranged between 0.50 and 1.00. Ranking of
      breeding strategies, based on the highest average genetic gain, was relatively
      insensitive to heritability, number of progeny per bull, and the relative
      importance of both environments, but was very sensitive to selection intensity.
      With more intense selection, running 2 environment-specific breeding programs was
      optimal for genetic correlations up to 0.70-0.80, but this strategy was less
      appropriate for situations where 1 of the 2 environments had a relative
      importance less than 10 to 20%. Results of this study can be used as guidelines
      to optimize breeding programs when breeding dairy cattle for different parts of
      the world.

PMID- 16606746
TI  - Association of the OLR1 gene with milk composition in Holstein dairy cattle.
AB  - Oxidized low-density lipoprotein receptor (OLR1) is the major protein that binds,
      internalizes, and degrades oxidized low-density lipoprotein. The role of OLR1 in
      lipid metabolism and the results of previous whole-genome scan studies prompted
      the investigation of OLR1 as a candidate gene affecting milk composition traits.
      Direct cDNA and genomic sequencing of OLR1 revealed 2 single nucleotide
      polymorphisms (SNP) in exon 4, 5 SNP in intron 4, and 1 in the 3' untranslated
      region (UTR). Four intragenic haplotypes comprising SNP positions 7,160, 7,161,
      7,278, 7,381, 7,409, 7,438, 7,512, and 8,232 were inferred. Haplotype analysis
      showed that one of the haplotypes was associated with a significant increase in
      fat yield and fat percentage. Single SNP analysis showed that allele C of SNP
      8,232 (in the 3'-UTR) had significant effects on fat yield and fat percentage,
      whereas SNP 7,160 and 7,161 (in exon 4) had no significant effects. Both single
      SNP and haplotype analyses indicate that SNP 8,232 in the 3'-UTR is associated
      with milk fat yield and percentage and it may be in linkage disequilibrium with
      the functional polymorphism. To provide support for the hypothesis that SNP 8,232
      is responsible for OLR1 expression, OLR1 expression levels in individuals bearing
      different genotypes were assessed. It was found that OLR1 expression was reduced
      in genotype AA individuals compared with CC and AC individuals, suggesting that A
      at position 8,232 may be the nucleotide causing decreased OLR1 expression. The 3'
      UTR polymorphism found in this study might control translation or stability of
      OLR1 mRNA.

PMID- 16606747
TI  - Short communication: A milk trait-associated polymorphism in the bovine growth
      hormone receptor gene does not affect receptor signaling.
AB  - Growth hormone (GH), also known as somatotropin, stimulates milk production in
      cows. At the tissue level, the action of GH is mediated by the GH receptor (GHR)
      and the receptor-activated intracellular signaling pathway involving Janus kinase
      2 (JAK2) and signal transducer and activator of transcription 5 (STAT5). A T/A
      nucleotide variation in exon 8 of the bovine GHR gene, resulting in a
      phenylalanine to tyrosine change in the transmembrane domain of the GHR protein,
      has been reported to be associated with a major effect on milk yield in cows. The
      objective of this study was to determine whether the 2 versions of GHR differ in
      mediating GH-induced STAT5 activation of gene expression. We created cDNA
      expression plasmids for the 2 versions of GHR and cotransfected each of them with
      a STAT5 expression plasmid and a luciferase reporter gene construct containing
      STAT5 binding sites into 2 different cell lines. Treatment of the transfected
      cells with various concentrations of GH triggered a dose-dependent increase in
      luciferase activity. However, the GH-induced luciferase activity was not
      different between the 2 GHR expression plasmids, indicating that the 2 GHR forms
      did not differ in mediating GH-induced STAT5 activation of gene expression. Thus,
      if the T/A polymorphism in exon 8 of the GHR gene has a causative effect on milk
      production, this effect is unlikely to be mediated by the JAK2-STAT5 pathway, the
      currently known major signaling pathway from the growth hormone receptor.

PMID- 16606748
TI  - Genetic correlations between milk production and health and fertility depending
      on herd environment.
AB  - High milk production in dairy cattle can have negative side effects on health and
      fertility traits. This paper explores the genetic relationship of milk yield with
      health and fertility depending on herd environment. A total of 71,720 lactations
      from heifers calving in 1997 to 1999 in the Netherlands were analyzed. Herd
      environment was described by 4 principal components: intensity, average
      fertility, farm size, and relative performance indicating whether herds had good
      (poor) health and fertility despite a high (low) production. Fertility was
      evaluated by days to first service and number of inseminations (NINS); somatic
      cell score was used as a measure of udder health. Data were analyzed with a
      multitrait reaction norm model. Genetic correlation within traits across
      environments ranged from 0.84 to unity. Genetic correlations of the 3 traits with
      milk yield were antagonistic but varied over environments. Genetic correlation of
      milk yield with days to first service varied from 0.30 in small herds to 0.48 in
      herds with low average fertility. Correlations with NINS varied from 0.18 in
      large herds to 0.64 in high fertility herds, and with somatic cell score from
      0.25 in herds with a high fertility relative to production to 0.47 in herds with
      a relative low fertility. Selection in environments of average value resulted in
      different predicted responses over environments. For example, selection for a
      decrease of NINS of 0.1 in an average production environment decreased milk yield
      by 35 kg in low production herds, but by 178 kg in high production herds.

PMID- 16606749
TI  - Genetic and phenotypic relationships among locomotion type traits, profit,
      production, longevity, and fertility in Spanish dairy cows.
AB  - The phenotypic and genetic relationships of 3 locomotion traits with profit,
      production, longevity, and fertility traits were studied to determine the
      importance of locomotion traits for dairy producers. Two data sets including
      official milk records and type classification scores of 62,293 cows, and
      reproductive records of 24,561 cows from the Basque and Navarra Autonomous
      Regions were analyzed. Higher scores for feet and legs (FL), foot angle (FA), and
      rear legs set (RLS) were positively related to production and functional traits,
      whereas fertility was not significantly affected. The cows that scored the
      highest for FL were $213/yr more profitable, produced 575 kg more milk per year,
      and remained in the herd for 307 more functional days than the cows scoring the
      lowest. Feet and legs was the trait most genetically correlated to profit,
      although a low value (0.10) was obtained, whereas RLS was the trait most
      correlated to milk production (0.12). Genetic correlations among FL, FA, RLS, and
      longevity traits (from -0.10 to 0.05) were low. Quadratic curves were the best
      fit for both profit and functional herd life for EBV of each of the 3 locomotion
      traits. Further studies dealing with profitability and lameness, instead of using
      conformation traits, could be performed directly if a larger data pool of
      lameness was routinely recorded.

PMID- 16606750
TI  - Influence of prion protein genotypes on milk production traits in Spanish Churra
      sheep.
AB  - The aim of this work was to analyze the possible relationships between milk
      production traits and prion protein genotypes in Spanish Churra sheep. For this
      purpose, 2 analyses were carried out. First, an association study was performed
      of the prion protein genotypes of 12,533 Churra ewes and their milk yield,
      protein percentage, fat percentage, and somatic cell score as phenotypes,
      followed by a quantitative trait loci screening on the chromosome where the prion
      protein gene was located in this population. The latter analysis was carried out
      using 8 genetic markers (7 microsatellites and the prion protein genotypes)
      spanning ovine chromosome 13 using a daughter design. Regarding genotype
      frequencies, the most frequent allele was ARQ (75.90%), which linked with a high
      susceptibility to scrapie, followed by the resistant haplotype, ARR (18.16 %).
      The frequency of the most susceptible allele, VRQ, was around 1%. No evidence of
      association or linkage between prion protein genotypes and milk traits has been
      detected in Churra sheep. These results indicate that increasing the ARR
      frequency in Churra population will not have an adverse effect on selection for
      milk traits included in the breeding objectives. However, the low allele
      frequencies for ARR should be considered in the initial stages to prevent
      possible bottlenecks in future genetic progress.

PMID- 16606751
TI  - Estimation of genetic correlations among countries in international dairy sire
      evaluations with structural models.
AB  - The increase in the number of participating countries and the lack of genetic
      ties between some countries has lead to statistical and computational
      difficulties in estimating the genetic (co)variance matrix needed for
      international sire evaluation of milk yield and other traits. Structural models
      have been proposed to reduce the number of parameters to estimate by exploiting
      patterns in the genetic correlation matrix. Genetic correlations between
      countries are described as a simple function of unspecified country
      characteristics that can be mapped in a space of limited dimensions. Two link
      functions equal to the exponential of minus the Euclidian distance between the
      coordinates of two countries and the exponential of minus the square of this
      Euclidian distance were used for the study on international simulated and field
      data. On simulated data, it was shown that structural models might allow an
      easier estimation of genetic correlations close to the border of the parameter
      space. This is not always possible with an unstructured model. On milk yield
      data, genetic correlations obtained from 22 countries for structural models based
      on 2 and 7 dimensions, respectively, were analyzed. Only a structural model with
      a large number of axes gave reasonable estimates of genetic correlations compared
      with correlations obtained for an unstructured model: 76.7% of correlations
      deviated by less than 0.030. Such a model reduces the number of parameters from
      231 genetic correlations to 126 coordinates. On foot angle data, large deviations
      were observed between genetic correlations estimated with an unstructured model
      and correlations estimated with a structural model, regardless of the number of
      axes taken into account.

PMID- 16606752
TI  - Genetic variation of Mycobacterium avium ssp. paratuberculosis infection in US
      Holsteins.
AB  - The objective of this study was to estimate genetic variability of Mycobacterium
      avium ssp. paratuberculosis infection in US Holsteins. Blood and fecal samples
      were collected primarily from daughters of 12 bulls in their second or third
      lactation. Routine disease testing of the sires documented that they were not
      infected. Herds without a "suspect" or positive ELISA (sample/positive ratio > or
      = 0.10) or positive fecal culture test were deleted from the data set. The
      remaining 4,603 cows from 238 herds and 46 sires were used to estimate
      heritability of M. paratuberculosis infection. Heritability was estimated with 3
      Johne's disease diagnostic tests: 1) fecal culture alone, 2) serum antibody ELISA
      alone, and 3) both tests (combined) with a positive animal defined as all animals
      with either a positive fecal culture or ELISA test. Four statistical models were
      used to estimate heritability: 1) linear (ELISA), 2) threshold (fecal culture and
      combined), 3) ordered threshold (ELISA), and 4) bivariate linear-threshold (ELISA
      fecal culture). A sire model and Bayesian approach using Markov chain Monte Carlo
      methods were used in each case. Heritability of infection based on the fecal
      culture test was 0.153 [posterior standard deviation (PSD) = 0.115]. Heritability
      with the ELISA was 0.159 (PSD = 0.090) with a linear model and 0.091 (PSD =
      0.053) with an ordered threshold model. Heritability of the combined tests was
      0.102 (PSD = 0.066). Heritability estimates of fecal culture and ELISA with the
      bivariate model varied slightly from estimates obtained with the univariate
      models (0.125 and 0.183, respectively), with a corresponding increase in
      precision (PSD = 0.096 and 0.082, respectively). This study demonstrates that
      exploitable genetic variation exists in dairy cattle for M. paratuberculosis
      infection susceptibility.

PMID- 16606753
TI  - The accuracy of seven mathematical functions in modeling dairy cattle lactation
      curves based on test-day records from varying sample schemes.
AB  - Daily milk yield over the course of the lactation follows a curvilinear pattern,
      so a suitable function is required to model this curve. In this study, 7
      functions (Wood, Wilmink, Ali and Schaeffer, cubic splines, and 3 Legendre
      polynomials) were used to model the lactation curve at the phenotypic level,
      using both daily observations and data from commonly used recording schemes. The
      number of observations per lactation varied from 4 to 11. Several criteria based
      on the analysis of the real error were used to compare models. The performance of
      models showed few discrepancies in the comparison criteria when daily or 4-weekly
      (with first test at days in milk 8) data by lactation were used. The performance
      of the Wood, Wilmink, and Ali and Schaeffer models were highly affected by the
      reduction of the sample dimension. The results of this work support the idea that
      the performance of these models depends on the sample properties but also shows
      considerable variation within the sampling groups.

PMID- 16606754
TI  - Adoption of security systems by dairy farms to address bioterrorist threats in
      the intermountain United States.
AB  - Data generated from a survey of western dairy farms was used to determine the
      characteristics of dairy farmers who have undertaken to improve security measures
      on their farms during the past 2 or 3 yr. The findings suggest that decisions to
      improve on-farm security are influenced by the producer's awareness of how to
      develop a security policy, and by the size of the dairy operation. The results
      also support the notion that farms may be vulnerable to bioterrorist attacks
      because most farmers do not believe it is important to establish on-farm security
      policies.

PMID- 16606755
TI  - Prediction of nitrogen excretion in dairy farms located in north Florida: a
      comparison of three models.
AB  - The increasing N concentrations in surface and groundwater in north Florida
      emphasize the need to identify sources of N loss and ways to reduce them. The
      amount of N excretion produced by dairy farms and deposited into the Suwannee
      River agro-ecosystem is being heavily scrutinized by regulatory agencies because
      it is believed to contribute significantly to the high N concentrations in water.
      Models developed by Van Horn and the USDA-Natural Resource and Conservation
      Service are used to estimate N balances on dairy farms. This study explores ways
      to improve these estimates by using dynamic simulation of N excretion over time.
      The Livestock Dynamic North Florida Dairy Farm model (LiDyNoFlo), which was
      created for this purpose, is described. The amount of N excretion on a dairy farm
      depends on crude protein in the diet, milk production, the presence of mature
      bulls and heifers, and seasonality of production. The LiDyNoFlo considered more
      variables than earlier models, and estimates of N excretion differed from those
      of other models. Comparisons consistently showed the LiDyNoFlo predictions of N
      excretion were between those predicted by the Van Horn model (upper end) and the
      Natural Resource and Conservation Service model (lower end). The LiDyNoFlo
      predicted that a 1,000-cow operation produced 324 kg of N excretion/d in February
      and 307 kg of N excretion/d in August because of seasonal milk production and
      herd dynamics. Seasonal differences in N excretion are important because they
      determine the opportunity for N recycling in the crop fields such that total N
      losses into the Suwannee River agro-ecosystem may be minimized.

PMID- 16606756
TI  - Development and daily management of an explicit strategy of nonuse of
      antimicrobial drugs in twelve Danish organic dairy herds.
AB  - Promotion of animal health and well-being at the individual animal and herd level
      is an important goal in organic farming. At the same time, chemical products
      affecting the natural balance among living organisms are prohibited in all areas
      of the organic farm. From an animal welfare point of view, however, no animal
      must suffer. Therefore, veterinary drugs are allowed under the European Union's
      regulations for organic farming, despite the fact that they are powerful cell
      toxins affecting both pathogenic and necessary bacteria, and as such in organic
      terminology, are regarded as "chemical" or "artificial" products. In this
      article, we present and discuss interviews with 12 Danish organic dairy producers
      who claim that minimized use or nonuse of antimicrobial drugs is an explicit
      goal. The dairy producers were at different levels with regard to reduced
      antimicrobial treatment. An explicit strategy of no antimicrobial treatments is
      based primarily on a long-term effort to improve herd health, and secondarily, on
      finding alternative treatments for diseased animals. Improved hygiene, outdoor
      access, use of nursing cows, and blinding of chronic mastitis quarters were the
      main techniques in developing a strategy of not using antimicrobial treatments in
      the herd by dairy producers. Producers' perception of disease changed from
      something unavoidable to a disturbing break in the daily rhythm that often could
      have been avoided. Change toward a nonantimicrobial strategy was gradual and
      stepwise. All dairy producers in this study desired to preserve the possibility
      of using antimicrobial drugs in emergencies.

PMID- 16606757
TI  - A systems comparison of once- versus twice-daily milking of pastured dairy cows.
AB  - The objective of this study was to compare the effect of milking frequency (once
      vs. twice-daily milking) and breed (Holstein-Friesians vs. Jerseys) on milk and
      milk solids (MS; milk fat + milk protein), yield per cow, milk composition,
      somatic cell count and lactation length; cow body weight, body condition score,
      and reproductive performance over a 4-yr period. Total cow numbers in each herd
      were 30, 35, 36, and 42 for Holstein-Friesians milked once or twice daily, and
      Jerseys milked once or twice daily, respectively. Forty hectares of pasture were
      subdivided into 4 smaller pastures of 10 ha each. Stocking rates for the once
      daily herds were 16.7% greater than the twice-daily herd in their respective
      breed. An increased stocking rate was chosen to achieve equal milk and MS per ha
      from the 2 milking frequencies. Annual milk, fat, protein, and lactose yields per
      cow were less for once-daily than for twice-daily milking. Interactions were
      detected between milking frequency and breed for annual milk, fat, protein, and
      lactose yields per cow, because Jerseys were relatively less affected by once
      daily than by twice-daily milking than Holstein-Friesians. Holstein-Friesian cows
      milked once daily produced 31.2% less milk and 29.4% less MS per cow than their
      twice-daily counterparts. In contrast, Jersey cows milked once daily produced
      22.1% less milk and 19.9% less MS per cow than their twice-daily counterparts.
      Milk per ha was 17.7 and 9% less for the once-daily Holstein-Friesians and once
      daily Jersey herds, respectively, compared with their twice-daily counterparts,
      because the greater stocking rate for the once-daily herds did not fully
      compensate for the milk loss per cow. Milking once daily increased somatic cell
      count throughout the year in both breeds. Cows milked once daily conceived 3 d
      earlier, took 5 d less from calving to conception, and needed 11% fewer
      controlled internal drug release devices than those milked twice daily. Milking
      once daily is a viable milking option for New Zealand farmers who are prepared to
      trade-off loss of MS income for increased time to accomplish other non-milking
      activities.

PMID- 16606758
TI  - Epstein-Barr virus and multiple sclerosis: evidence of association from a
      prospective study with long-term follow-up.
AB  - OBJECTIVE: To determine whether serum titers of anti-Epstein-Barr virus (EBV)
      antibodies are elevated in blood specimens collected up to 30 years prior to
      onset of multiple sclerosis (MS). METHODS: Individuals with MS were identified
      among members of the Kaiser Permanente Northern California health plan who
      participated in the multiphasic examinations administered between 1965 and 1974.
      Stored serum samples were used to compare anti-EBV antibody titers in 42
      individuals who developed MS with age-matched and sex-matched controls. RESULTS:
      The geometric mean titers of antibodies to the Epstein-Barr nuclear antigen
      (EBNA) complex and its component EBNA-1 were significantly higher in the MS cases
      when compared with matched controls. The relative risk of MS associated with a 4
      fold increase in antibody titers was 2.1 (95% confidence interval, 1.1-3.8) for
      the EBNA complex and 1.8 (95% confidence interval, 1.1-2.9) for EBNA-1.
      Elevations of antibody titers to the EBNA complex and EBNA-1 among MS cases first
      occurred between 15 to 20 years before the onset of symptoms and persisted
      thereafter. CONCLUSION: The elevation of anti-EBV titers is probably an early
      event in the pathogenesis of MS and is unlikely to be the result of an aspecific
      immune dysregulation.

PMID- 16606759
TI  - Frontotemporal lobar degeneration with motor neuron disease: a clinical and
      pathological spectrum.

PMID- 16606760
TI  - Effects of anticonvulsant drugs on life span.
AB  - Aging is characterized by widespread degenerative changes in tissue morphology
      and function and an increase in the incidence of human diseases such as cancer,
      stroke, and Alzheimer disease. Findings from recent genetic studies suggest that
      molecular mechanisms that influence life span are evolutionarily conserved, and
      interventions that extend the life span of model organisms such as worms and
      flies are likely to have similar effects on vertebrates such as humans. However,
      little progress has been made in identifying drugs that delay aging. We
      identified 3 pharmacologic compounds, ethosuximide, trimethadione, and 3,3
      diethyl-2-pyrrolidinone, that extend lifespan and delay age-related degenerative
      changes in the nematode worm Caenorhabditis elegans. All 3 compounds are
      anticonvulsants that modulate neural activity in vertebrates, and ethosuximide
      and trimethadione are used to treat absence seizures in humans. We discuss
      existing evidence that these drugs might also delay vertebrate aging and suggest
      experiments that could test this hypothesis. Genetic and cell ablation studies
      conducted with model organisms have demonstrated connections between the nervous
      system and aging. Our studies provide additional support for the hypothesis that
      neural activity plays a role in lifespan determination, since ethosuximide and
      trimethadione regulated neuromuscular activity in nematodes. Our findings suggest
      that the lifespan extending activity of these compounds is related to the
      anticonvulsant activity, implicating neural activity in the regulation of aging.
      We also discuss models that explain how the nervous system influences lifespan.

PMID- 16606761
TI  - Emerging pharmacotherapies for Creutzfeldt-Jakob disease.
AB  - Only a few years ago, pharmacotherapy of Creutzfeldt-Jakob disease was
      inconceivable. The enigmatic prion agent causing Creutzfeldt-Jakob disease,
      consisting solely of a misfolded conformational isoform, the scrapie prion
      protein, of the normal cellular prion protein was considered hard to treat by
      routine drug development. However, huge progress has been achieved in recent
      years, demonstrating principal reversibility of the neuropathological features
      and protection from clinical symptoms in animal models and introducing potential
      pharmaceutical agents. Among the most promising ones, antibodies have been shown
      to be protective against prion disease and heterocyclic small-molecule compounds
      have been proposed as antiprion lead compounds, initiating clinical trials.

PMID- 16606762
TI  - Clinically undetected motor neuron disease in pathologically proven
      frontotemporal lobar degeneration with motor neuron disease.
AB  - BACKGROUND: Frontotemporal lobar degeneration with motor neuron disease (FTLD
      MND) is a pathological entity characterized by motor neuron degeneration and
      frontotemporal lobar degeneration. The ability to detect the clinical signs of
      dementia and motor neuron disease in pathologically confirmed FTLD-MND has not
      been assessed. OBJECTIVES: To determine if all cases of pathologically confirmed
      FTLD-MND have clinical evidence of frontotemporal dementia and motor neuron
      disease, and to determine the possible reasons for misdiagnosis. METHOD: Review
      of historical records and semiquantitative analysis of the motor and extramotor
      pathological findings of all cases of pathologically confirmed FTLD-MND. RESULTS:
      From a total of 17 cases of pathologically confirmed FTLD-MND, all had clinical
      evidence of frontotemporal dementia, while only 10 (59%) had clinical evidence of
      motor neuron disease. Semiquantitative analysis of motor and extramotor
      pathological findings revealed a spectrum of pathological changes underlying FTLD
      MND. Hippocampal sclerosis, predominantly of the subiculum, was a significantly
      more frequent occurrence in the cases without clinical evidence of motor neuron
      disease (P<.01). In addition, neuronal loss, gliosis, and corticospinal tract
      degeneration were less severe in the other 3 cases without clinical evidence of
      motor neuron disease. CONCLUSIONS: Clinical diagnostic sensitivity for the
      elements of FTLD-MND is modest and may be affected by the fact that FTLD-MND
      represents a spectrum of pathological findings, rather than a single homogeneous
      entity. Detection of signs of clinical motor neuron disease is also difficult
      when motor neuron degeneration is mild and in patients with hippocampal
      sclerosis.

PMID- 16606763
TI  - Treatment of Wilson disease with ammonium tetrathiomolybdate: IV. Comparison of
      tetrathiomolybdate and trientine in a double-blind study of treatment of the
      neurologic presentation of Wilson disease.
AB  - OBJECTIVE: To compare tetrathiomolybdate and trientine in treating patients with
      the neurologic presentation of Wilson disease for the frequency of neurologic
      worsening, adverse effects, and degree of neurologic recovery. DESIGN: A
      randomized, double-blind, controlled, 2-arm study of 48 patients with the
      neurologic presentation of Wilson disease. Patients either received 500 mg of
      trientine hydrochloride 2 times per day or 20 mg of tetrathiomolybdate 3 times
      per day with meals and 20 mg 3 times per day between meals for 8 weeks. All
      patients received 50 mg of zinc 2 times per day. Patients were hospitalized for 8
      weeks, with neurologic and speech function assessed weekly; discharged taking 50
      mg of zinc 3 times per day, and returned annually for follow-up. SETTING: A
      university hospital referral setting. PATIENTS: Primarily newly diagnosed
      patients with Wilson disease presenting with neurologic symptoms who had not been
      treated longer than 4 weeks with an anticopper drug. INTERVENTION: Treatment with
      either trientine plus zinc or tetrathiomolybdate plus zinc. MAIN OUTCOME
      MEASURES: Neurologic function was assessed by semiquantitative neurologic and
      speech examinations. Drug adverse events were evaluated by blood cell counts and
      biochemical measures. RESULTS: Six of 23 patients in the trientine arm and 1 of
      25 patients in the tetrathiomolybdate arm underwent neurologic deterioration
      (P<.05). Three patients receiving tetrathiomolybdate had adverse effects of
      anemia and/or leukopenia, and 4 had further transaminase elevations. One patient
      receiving trientine had an adverse effect of anemia. Four patients receiving
      trientine died during follow-up, 3 having shown initial neurologic deterioration.
      Neurologic and speech recovery during a 3-year follow-up period were quite good.
      CONCLUSION: Tetrathiomolybdate is a better choice than trientine for preserving
      neurologic function in patients who present with neurologic disease.

PMID- 16606764
TI  - Protracted ictal confusion in elderly patients.
AB  - BACKGROUND: Ictal confusion, particularly if protracted, often presents a
      diagnostic challenge. OBJECTIVES: To define protracted ictal confusion in elderly
      patients and to characterize its features and outcome. DESIGN: Case series.
      SETTING: Neurology outpatient and emergency departments at 2 tertiary care
      centers. PATIENTS: Consecutive series of 22 ambulatory patients with acute ictal
      confusion. MAIN OUTCOME MEASURES: Duration of ictal confusion was correlated with
      age and lesions noted on cerebral images and videoelectroencephalographic
      studies. RESULTS: The ictal basis underlying confusion was not recognized for up
      to 5 days in 22 patients (mean +/- SD age, 70 +/- 8.5 years). Twenty patients had
      partial complex status epilepticus, and 2 patients had newly diagnosed primary
      generalized status epilepticus. Motor movements were not present in either group,
      although reduced mood states and ictal neglect were noted in some patients.
      Fifteen patients had previous episodes (2-10) of protracted ictal confusion. Once
      identified, treatment reversed confusion, and eventually patients were discharged
      to home, although a few patients sustained persistent reduction in baseline
      cognition. CONCLUSIONS: Protracted ictal confusion is often not considered in the
      ambulatory elderly patient, with resulting delay in diagnosis.
      Electroencephalographic and videoelectroencephalographic studies performed while
      the patient is experiencing symptoms are crucial to early diagnosis and timely
      management.

PMID- 16606765
TI  - Correlation of global N-acetyl aspartate with cognitive impairment in multiple
      sclerosis.
AB  - BACKGROUND: Whole-brain N-acetyl aspartate (NAA), a measure of neuronal function,
      can be assessed by multislice echo-planar spectroscopic imaging. OBJECTIVE: To
      test the hypothesis that the global brain NAA/creatine (Cr) ratio is a better
      predictor of cognitive dysfunction in multiple sclerosis than conventional
      magnetic resonance imaging measures. DESIGN: Survey. SETTING: Research-oriented
      hospitals. PATIENTS: Twenty patients, 16 women and 4 men (mean age, 36 years),
      with early relapsing-remitting multiple sclerosis (mean Expanded Disability
      Status Scale score, 2.5). MAIN OUTCOME MEASURES: Correlation between the global
      NAA/Cr ratio and a cognitive dysfunction factor comprising 16 measures from an
      extensive neuropsychological test battery that best distinguished patients with
      multiple sclerosis from healthy control subjects. RESULTS: A significant partial
      correlation between the global NAA/Cr ratio and the cognitive dysfunction factor
      was found (partial r = 0.62, P = .01), and 9 cognitively impaired patients had
      significantly lower global NAA/Cr ratios than 11 unimpaired patients (P = .04).
      No significant correlations were found between the cognitive dysfunction factor
      and conventional magnetic resonance imaging measures (ie, brain parenchymal
      fraction and lesion volume). CONCLUSIONS: Multislice echo-planar spectroscopic
      imaging provides global metabolic measures that distinguish between cognitively
      impaired and unimpaired patients with multiple sclerosis and correlate with a
      global cognitive measure. Standardization of the technique is needed, and larger
      scale studies that include healthy controls are suggested.

PMID- 16606766
TI  - Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer
      disease.
AB  - BACKGROUND: Immunoreactivity for several chemokines and for their related
      receptors has been demonstrated in resident cells of the central nervous system,
      and the up-regulation of some of them is associated with pathological changes
      found in Alzheimer disease (AD). OBJECTIVE: To determine interferon-gamma
      inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and
      interleukin 8 (IL-8) levels in cerebrospinal fluid (CSF) from subjects with
      amnestic mild cognitive impairment (MCI) and patients with AD as compared with
      age-matched controls. PATIENTS: Thirty-eight subjects with amnestic MCI, 36
      patients with AD, and 41 age-matched subjects with noninflammatory affections of
      the nervous system. DESIGN: Evaluation of CSF chemokine production at time of
      diagnosis of MCI and AD; correlation with clinical and personal data.
      Longitudinal evaluation of subjects with MCI until conversion to AD. RESULTS:
      Cerebrospinal fluid IP-10 concentration was significantly increased in patients
      with MCI and mild AD but not in patients with severe AD (Mini-Mental State
      Examination score <15), whereas MCP-1 and IL-8 levels were increased in patients
      with MCI and all patients with AD. A significant positive correlation between
      Mini-Mental State Examination score and CSF IP-10 or MCP-1 concentration was
      observed in patients with AD. No correlation between IP-10 levels and age was
      found, whereas MCP-1 and IL-8 levels correlated positively with age. Out of 38
      subjects with MCI, 19 developed AD within a 1- to 3-year follow-up. CONCLUSIONS:
      The presence of inflammatory molecules is likely to be a very early event in AD
      pathogenesis, even preceding the clinical onset of the disease, as demonstrated
      by subjects with MCI who developed AD over time. Interferon-gamma-inducible
      protein 10 is specifically increased in MCI and seems to decrease with the
      progression of AD, whereas MCP-1 and IL-8 are up-regulated also in late stages of
      the disease, suggesting a role in phases in which neurodegeneration is prevalent.

PMID- 16606767
TI  - Case-control study of the parkin gene in early-onset Parkinson disease.
AB  - BACKGROUND: Mutations in parkin are estimated to account for as much as 50% of
      familial Parkinson disease (PD) and 18% of sporadic PD. Single heterozygous
      mutations in parkin in both familial and sporadic cases may also increase
      susceptibility to PD. To our knowledge, all previous studies have been restricted
      to PD cases; this is the first study to systematically screen the parkin coding
      regions and exon deletions and duplications in controls. OBJECTIVE: To determine
      the frequency and spectrum of parkin variants in early-onset PD cases (aged < or
      =50 years) and controls participating in a familial aggregation study. PATIENTS
      AND METHODS: We sequenced the parkin gene in 101 cases and 105 controls. All
      cases and controls were also screened for exon deletions and duplications by
      semiquantitative multiplex polymerase chain reaction. RESULTS: Thirteen (12.9%
      [95% confidence interval, 7%-21%]) of the 101 cases had a previously described
      parkin mutation: 1 was homozygous, 11 were heterozygous, and 1 was a compound
      heterozygote. The mutations Arg42Pro (exon 2) and Arg275Trp (exon 7) were
      recurrent. The previously reported synonymous substitution Leu261Leu (c.884A>G)
      was identified in 4 (3.9%) of 101 cases and 2 (2%) of 105 controls (P = .44).
      Excluding the synonymous substitution Leu261Leu (heterozygotes), 10 (9.9% [95%
      confidence interval, 4.6%-17.5%]) carried mutations. CONCLUSIONS: The frequency
      of mutations among cases that were not selected based on family history of PD is
      similar to what has previously been reported in sporadic PD. The similar
      frequency of Leu261Leu in cases and controls suggests it is a normal variant
      rather than a disease-associated mutation. We confirmed that heterozygous parkin
      mutations may increase susceptibility for early-onset PD.

PMID- 16606768
TI  - Cerebellar ataxia with spasmodic cough: a new form of dominant ataxia.
AB  - BACKGROUND: Although mentioned in most series, "pure" autosomal dominant
      cerebellar ataxias, except spinocerebellar ataxia type 6, are difficult to
      differentiate on clinical grounds. OBJECTIVE: To describe Portuguese families
      with a peculiar pure form of dominant ataxia that, to our knowledge, has never
      been documented before and in which cerebellar signs are preceded by spasmodic
      cough. PATIENTS: Through a population-based survey of hereditary ataxias in
      Portugal, we identified 19 patients in 6 families with this particular disorder.
      RESULTS: The majority of patients had a pure late-onset ataxia with a benign
      evolution. In all of the families, attacks of spasmodic coughing preceded ataxia
      for 1 to 3 decades and were a reliable marker of the disease. In Portugal, this
      form of ataxia accounts for 2.7% of all of the dominant ataxias. CONCLUSIONS: The
      families that we describe shared some relevant clinical and imagiological
      features with spinocerebellar ataxia type 5 and the recently described
      spinocerebellar ataxia type 20, allelic to spinocerebellar ataxia type 5.
      Spinocerebellar ataxia types 5 and 20 could be different phenotypic expressions
      of the same molecular disorder. The association of a dominant ataxia with
      spasmodic cough is rare but probably underdiagnosed.

PMID- 16606769
TI  - Can selection of rapidly progressing patients shorten clinical trials in
      amyotrophic lateral sclerosis?
AB  - BACKGROUND: The marked variability in progression of amyotrophic lateral
      sclerosis (ALS) requires large numbers of patients to detect a significant effect
      in current clinical trial designs. OBJECTIVE: To test the utility of a lead-in
      period to assess rate of progression so that patients with rapidly progressive
      ALS can be selected for subsequent clinical trials. DESIGN: Prospective study.
      SETTING: The ALS Center, University of Lisbon, Lisbon, Portugal. PATIENTS: Fifty
      seven consecutively recruited patients assessed at diagnosis and 3 months later
      (end of lead-in period). INTERVENTIONS: Change in ALS Functional Rating Scale
      (ALS-FRS) score was analyzed to establish a statistically significant cutoff
      point to define patients with rapid (group 1) or slow (group 2) progression.
      Patients from both groups were reexamined 1 and 3 months after the lead-in
      period. MAIN OUTCOME MEASURES: Changes in ALS-FRS score, motor unit number
      estimation, and neurophysiologic index, and resultant grouping of patients
      according to rate of progression at 1 and 3 months. RESULTS: Both the 80th
      percentile and 2 SDs above the mean of the change in ALS-FRS score identified the
      same patients. Twelve patients showed rapid progression (group 1) and 45 showed
      slow progression (group 2). One month after the lead-in period there was a
      significant reduction in ALS-FRS score, motor unit number estimation, and
      neurophysiologic index in group 1, and after 3 months all these measurements
      changed significantly in both groups. CONCLUSIONS: This strategy of selecting
      patients with rapidly progressing ALS for inclusion in exploratory, short phase
      II clinical trials offers substantial savings in costs and time, and could
      accelerate the process of testing potentially useful drugs for the treatment of
      ALS.

PMID- 16606770
TI  - Brain response to one's own name in vegetative state, minimally conscious state,
      and locked-in syndrome.
AB  - BACKGROUND: A major challenge in the management of severely brain-injured
      patients with altered states of consciousness is to estimate their residual
      perception of the environment. OBJECTIVE: To investigate the integrity of
      detection of one's own name in patients in a behaviorally well-documented
      vegetative state (VS), patients in a minimally conscious state (MCS), and
      patients with locked-in syndrome. DESIGN: We recorded the auditory evoked
      potentials to the patient's own name and to 7 other equiprobable first names in
      15 brain-damaged patients. RESULTS: A P3 component was observed in response to
      the patient's name in all patients with locked-in syndrome, in all MCS patients,
      and in 3 of 5 patients in a VS. P3 latency was significantly (P<.05) delayed for
      MCS and VS patients compared with healthy volunteers. CONCLUSIONS: These results
      suggest that partially preserved semantic processing could be observed in
      noncommunicative brain-damaged patients, notably for the detection of salient
      stimuli, such as the subject's own name. This function seems delayed in MCS and
      (if present) in VS patients. More important, a P3 response does not necessarily
      reflect conscious perception and cannot be used to differentiate VS from MCS
      patients.

PMID- 16606771
TI  - Stroke and memory performance in elderly persons without dementia.
AB  - BACKGROUND: There are conflicting data showing that stroke is associated with a
      higher risk of dementia and a more severe decline in persons with cognitive
      impairment. However, it remains unclear if cerebrovascular disease is directly
      related to cognitive decline in the absence of cognitive impairment or dementia.
      OBJECTIVE: To examine the association between stroke and changes in cognitive
      function over time in elderly persons without dementia at baseline. DESIGN: The
      results of neuropsychological tests from several intervals over a 5-year period
      were clustered into domains of memory, abstract/visuospatial, and language in
      1271 elderly persons without dementia or cognitive decline. Stroke was related to
      the slope of performance in each cognitive domain using generalized estimating
      equations. RESULTS: Memory performance declined over time, while
      abstract/visuospatial and language performance remained stable during the study
      period. Stroke was associated with a more rapid decline in memory performance,
      while there was no association between stroke and decline in
      abstract/visuospatial or language performance. The association between stroke and
      decline in memory performance was strongest for men and for persons without an
      APOEepsilon4 allele. A significant association between stroke and decline in
      abstract/visuospatial performance was also observed for persons without the
      APOEepsilon4 allele. CONCLUSION: A history of stroke is related to a progressive
      decline in memory and abstract/visuospatial performance, especially among men and
      those without an APOEepsilon4 allele.

PMID- 16606772
TI  - Phenotypic commonalities in familial and sporadic Parkinson disease.
AB  - BACKGROUND: Parkinson disease (PD) is a clinically well-documented
      neurodegenerative disorder. However, the mechanism or mechanisms of its
      phenotypic expressions are still unknown. OBJECTIVE: To compare phenotypes by
      examining demographic and clinical features of patients with familial PD and
      sporadic PD and with or without a family history of PD. DESIGN: Historical review
      of patients with sporadic PD in clinic-based samples and individual patients
      diagnosed with PD from families whose linkage to mutations or loci has been
      identified. SETTING: Movement disorder clinic in a referral center. PATIENTS: A
      total of 1277 patients with sporadic PD and 40 patients with familial PD. MAIN
      OUTCOME MEASURES: Clinical features, including distribution by sex, initial motor
      symptom, location of initial motor symptom, and frequency of asymmetric motor
      symptoms. RESULTS: Despite different etiologic backgrounds, both familial and
      sporadic PD exhibited several interesting commonalities, including a higher
      incidence in men, tremor as the initial motor symptom (predominantly involving
      the upper extremities), and asymmetric parkinsonism during disease course.
      CONCLUSIONS: The increased incidence of parkinsonism in men with familial PD
      suggests that the sex disparity is more likely the result of a protective effect
      against development of PD in women than of an increased risk in men that is
      associated with environmental factors. Phenotypic similarity among familial and
      sporadic PD indicates that a similar topographic distribution of the
      nigrostriatal lesion exists in patients with either form of PD regardless of
      apparent genetic influence.

PMID- 16606773
TI  - Motor score of the Unified Parkinson Disease Rating Scale as a good predictor of
      Lewy body-associated neuronal loss in the substantia nigra.
AB  - BACKGROUND: How well the motor symptoms assessed by the motor section of the
      Unified Parkinson Disease Rating Scale (UPDRS3) reflect the neuronal loss
      observed in the substantia nigra is not known. OBJECTIVE: To study the
      relationships among the motor symptoms assessed by the UPDRS3, Lewy body
      associated neuronal loss in the substantia nigra, and duration of disease.
      DESIGN: Longitudinal, prospective, clinicopathological study. SETTING: Long-term
      care facility of a university hospital. PATIENTS: Eighteen elderly patients with
      a parkinsonian syndrome, studied prospectively but selected post mortem on the
      basis of the presence of Lewy bodies, and 5 age-matched control subjects.
      METHODS: One map of a section of the substantia nigra, indicating the location of
      all the nucleolated neuronal profiles, was drawn for each case. Neuronal density
      was estimated using a tessellation method. The relationship between time and
      neuronal loss and between neuronal loss and motor symptoms (assessed by the
      UPDRS3) was studied by means of regression analysis, using linear and exponential
      models. RESULTS: The neuronal density was linearly linked with the UPDRS3 score
      (r = -0.83 [P<.001]). Each point added to the UPDRS3 score corresponded to an
      estimated loss of 25 neurons/mm(3). The density of neuronal profiles in the
      substantia nigra decreased exponentially with time (r = -0.73 [P<.001]).
      Extrapolation of the curve suggested a presymptomatic phase of 5 years.
      CONCLUSION: The UPDRS3 score is linearly linked to neuronal density, which, in
      Lewy body diseases, decreases exponentially with time at a similar pace in this
      series of elderly patients and in the younger patients described in the
      literature.

PMID- 16606774
TI  - Devic disease with brainstem lesions.
AB  - We describe a patient who suffered from an unusually severe form of neuromyelitis
      optica with a hyperacute time-course evolution requiring mechanical ventilation
      within 3 days. The patient died after 72 days and autopsy showed major spinal
      cord, optic nerve, and brainstem necrosis, and multifocal necrotic lesions on the
      cerebellum and cerebral white matter.

PMID- 16606775
TI  - Cerebellar ataxia with progressive improvement.
AB  - BACKGROUND: Nonprogressive cerebellar ataxias are characterized by a persistent,
      nonprogressive ataxia associated with cognitive impairment. Cerebellar hypoplasia
      on imaging is variable but is not predictive of the degree of ataxia or cognitive
      impairment. OBJECTIVE: To describe a family with a nonprogressive cerebellar
      ataxia associated with cognitive and motor impairments that improve with age.
      DESIGN: Genetic study in a family with nonprogressive cerebellar ataxia. Clinical
      and imaging features are also described. SETTING: Community hospital. PATIENTS:
      Both parents and 3 children from an affected family. MAIN OUTCOME MEASURES:
      Clinical features, magnetic resonance imaging findings, and genetic findings.
      RESULTS: A genome-wide single nucleotide polymorphism screen did not show clear
      linkage to known spinocerebellar ataxia loci, in particular spinocerebellar
      ataxia type 15. Repeat spinocerebellar ataxia loci expansions were excluded.
      Magnetic resonance images of all affected individuals demonstrated cerebellar
      vermian abnormalities. CONCLUSIONS: These findings suggest that nonprogressive
      cerebellar ataxia is genetically heterogeneous and, when associated with gradual
      improvement in cognition and motor skills, likely represents a separate, distinct
      clinical entity.

PMID- 16606776
TI  - Visual hallucinations during visual recovery after central retinal artery
      occlusion.
AB  - BACKGROUND: Charles Bonnet syndrome is characterized by complex, formed visual
      hallucinations that occur in patients without psychiatric disorders. To the best
      of our knowledge, it has not been described following central retinal artery
      occlusion. OBJECTIVE: To describe 2 patients who experienced formed visual
      hallucinations characteristic of Charles Bonnet syndrome after sudden, severe
      visual loss precipitated by central retinal artery occlusion. PATIENTS: Two
      patients, aged 77 and 63 years respectively, experienced sudden deterioration of
      vision following central retinal artery occlusion. Formed visual hallucinations
      occurred in patient 1 six days later and in patient 2 two days later. RESULTS:
      The hallucinations appeared both within and at the borders of the patients'
      residual intact visual fields. They occurred during periods when the patients
      experienced partial visual recovery associated with enlargement of their visual
      fields. The visual recovery and hallucinations both ceased at the same time.
      CONCLUSIONS: We propose that the hallucinations are likely the result of
      deafferentation and their occurrence during visual recovery suggests that they
      are a correlate of visual system plasticity.

PMID- 16606777
TI  - Pure autonomic failure with altered dopamine transporter imaging.

PMID- 16606778
TI  - A head bulge.

PMID- 16606779
TI  - Multiple gas-forming brain microabscesses due to Klebsiella pneumoniae.

PMID- 16606780
TI  - Not every patient with multiple sclerosis should be treated at time of diagnosis.

PMID- 16606782
TI  - Early multiple sclerosis: to treat or not to treat?

PMID- 16606781
TI  - Most patients with multiple sclerosis or a clinically isolated demyelinating
      syndrome should be treated at the time of diagnosis.

PMID- 16606783
TI  - The rise and fall of borax as an antiepileptic drug.
AB  - Five hundred eighty-six patients with epilepsy were treated with borax (hydrated
      sodium tetraborate) between 1912 and 1948 at the Kolonien Filadelfia Epilepsy
      Hospital, Dianalund, Denmark. A rough estimation shows that less than 5%
      experienced a more than 50% reduction in the total number of seizures. Charts
      were reviewed to find a connection between the concept of Bacillus epilepticus
      (1916) and the so-called renaissance of borax treatment described in 1923, and to
      find an explanation for the popularity of this seemingly ineffective
      antiepileptic drug.

PMID- 16606784
TI  - Internuclear ophthalmoplegia.

PMID- 16606785
TI  - Interferon beta-1a treatment and African Americans.

PMID- 16606787
TI  - Defending eponyms.

PMID- 16606786
TI  - Delusions and hallucinations in Alzheimer disease.

PMID- 16606788
TI  - Role of endogenous Fas (CD95/Apo-1) ligand in balloon-induced apoptosis,
      inflammation, and neointima formation.
AB  - BACKGROUND: Fas (CD95/Apo-1) ligand (FasL)-induced apoptosis in Fas-bearing cells
      is critically involved in modulating immune reactions and tissue repair.
      Apoptosis has also been described after mechanical vascular injury such as
      percutaneous coronary intervention. However, the relevance of cell death in this
      context of vascular repair remains unknown. METHODS AND RESULTS: To determine
      whether FasL-induced apoptosis is causally related to neointimal lesion
      formation, we subjected FasL-deficient (generalized lymphoproliferative disorder
      [gld], C57BL/6J) and corresponding wild-type (WT) mice to carotid balloon
      distension injury, which induces marked endothelial denudation and medial cell
      death. FasL expression in WT mice was induced in injured vessels compared with
      untreated arteries (P<0.05; n=5). Conversely, absence of functional FasL in gld
      mice decreased medial and intimal apoptosis (terminal deoxynucleotidyltransferase
      mediated dUTP nick end labeling [TUNEL] index) at 1 hour and 7 days after balloon
      injury (P<0.05; n=6). In addition, peritoneal macrophages isolated from gld mice
      showed no apoptosis and enhanced migration (P<0.05; n=4). In parallel, we
      observed increased balloon-induced macrophage infiltrations (anti-CD68) in
      injured arteries of FasL-deficient animals (P<0.05; n=6). Together with enhanced
      proliferation (bromodeoxyuridine index; P<0.05), these events resulted in a
      further increase in medial and neointimal cells (P<0.01; n=8) with thickened
      neointima in gld mice (intima/media ratio, x3.8 of WT; P<0.01). CONCLUSIONS: Our
      data identify proapoptotic and antiinflammatory effects of endogenous FasL as
      important factors in the process of neointimal lesion formation after balloon
      injury. Moreover, they suggest that activation of FasL may decrease neointimal
      thickening after percutaneous coronary intervention.

PMID- 16606789
TI  - A tailored approach to catheter ablation of paroxysmal atrial fibrillation.
AB  - BACKGROUND: Because the genesis of atrial fibrillation (AF) is multifactorial and
      variable, an ablation strategy that involves pulmonary vein isolation and/or a
      particular set of ablation lines may not be equally effective or efficient in all
      patients with AF. A tailored strategy that targets initiators and drivers of AF
      is a possible alternative to a standardized lesion set. METHODS AND RESULTS:
      Catheter ablation was performed in 153 consecutive patients (mean age, 56+/-11
      years) with symptomatic paroxysmal AF with the use of an 8-mm tip radiofrequency
      ablation catheter. The esophagus was visualized with barium. The pulmonary veins
      and left atrium were mapped during spontaneous or induced AF. Arrhythmogenic
      pulmonary veins were isolated or encircled. If AF was still present or inducible,
      complex electrograms in the left atrium, coronary sinus, and superior vena cava
      were targeted for ablation. The end point of ablation was absence of frequent
      atrial ectopy and spontaneous AF during isoproterenol infusion and
      noninducibility of AF. Routine energy applications near the esophagus were
      avoided. During follow-up, left atrial flutter developed in 19% of patients and
      was still present in 10% at >12 weeks of follow-up. A repeat ablation procedure
      was performed in 18% of patients. During a mean follow-up of 11+/-4 months, 77%
      of patients were free from AF and/or atrial flutter without antiarrhythmic drug
      therapy. Pericardial tamponade or transient neurological events occurred in 2% of
      procedures. CONCLUSIONS: A tailored ablation strategy that only targets triggers
      and drivers of AF is feasible and eliminates paroxysmal AF in approximately 80%
      of patients.

PMID- 16606790
TI  - Proarrhythmic potential of mesenchymal stem cell transplantation revealed in an
      in vitro coculture model.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are bone marrow stromal cells that are
      in phase 1 clinical studies of cellular cardiomyoplasty. However, the
      electrophysiological effects of MSC transplantation have not been studied.
      Although improvement of ventricular function would represent a positive outcome
      of MSC transplantation, focal application of stem cells has the potential
      downside of creating inhomogeneities that may predispose the heart to reentrant
      arrhythmias. In the present study we use an MSC and neonatal rat ventricular
      myocyte (NRVM) coculture system to investigate potential proarrhythmic
      consequences of MSC transplantation into the heart. METHODS AND RESULTS: Human
      MSCs were cocultured with NRVMs in ratios of 1:99, 1:9, and 1:4 and optically
      mapped. We found that conduction velocity was decreased in cocultures compared
      with controls, but action potential duration (APD80) was not affected. Reentrant
      arrhythmias were induced in 86% of cocultures containing 10% and 20% MSCs (n=36)
      but not in controls (n=7) or cocultures containing only 1% MSCs (n=4).
      Immunostaining, Western blot, and dye transfer revealed the presence of
      functional gap junctions involving MSCs. CONCLUSIONS: Our results suggest that
      mixtures of MSCs and NRVMs can produce an arrhythmogenic substrate. The mechanism
      of reentry is probably increased tissue heterogeneity resulting from electric
      coupling of inexcitable MSCs with myocytes.

PMID- 16606791
TI  - Cross talk between endothelial and smooth muscle cells in pulmonary hypertension:
      critical role for serotonin-induced smooth muscle hyperplasia.
AB  - BACKGROUND: The mechanism of pulmonary artery smooth muscle cell (PA-SMC)
      hyperplasia in idiopathic pulmonary artery hypertension (iPH) may involve both an
      inherent characteristic of PA-SMCs and abnormal control by external stimuli. We
      investigated the role of pulmonary microvascular endothelial cells (P-ECs) in
      controlling PA-SMC growth. METHODS AND RESULTS: Serum-free medium of quiescent P
      ECs elicited marked PA-SMC proliferation, and this effect was greater with P-ECs
      from patients with iPH than from control subjects and greater with PA-SMCs from
      these patients than from control subjects. Fluoxetine, which inhibits serotonin
      induced mitogenesis by blocking the serotonin transporter, and p
      chlorophenylalanine, which inhibits serotonin synthesis by blocking tryptophan
      hydroxylase (TPH), caused a similar 60% reduction in the growth-promoting effect
      of P-EC media, whereas endothelin receptor blockers had no effect. Assays of TPH
      activity in P-EC medium based on p-chlorophenylalanine-sensitive 5
      hydroxytryptophan accumulation or serotonin determination indicated serotonin
      synthesis by P-ECs and an increase in this TPH-dependent process in iPH.
      Expression of the tph1 gene encoding the peripheral form of the TPH enzyme was
      increased in lungs and P-ECs from patients with iPH. Lung TPH1 immunostaining was
      confined to the pulmonary vessel intima. CONCLUSIONS: P-ECs produce paracrine
      factors governing PA-SMC growth. Serotonin, the main P-EC-derived growth factor,
      is overproduced in iPH and contributes to PA-SMC hyperplasia.

PMID- 16606792
TI  - Heparins increase endothelial nitric oxide bioavailability by liberating vessel
      immobilized myeloperoxidase.
AB  - BACKGROUND: Neutrophils and monocytes are centrally linked to vascular
      inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as
      an important mechanistic participant in impaired vasomotor function. MPO binds to
      and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and
      MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of
      endothelium-derived nitric oxide (NO) and impairment of endothelial function in
      animal models. In the present study, we investigated whether heparin mobilizes
      MPO from vascular compartments in humans and defined whether this translates into
      increased vascular NO bioavailability and function. METHODS AND RESULTS: Plasma
      MPO levels before and after heparin administration were assessed by ELISA in 109
      patients undergoing coronary angiography. Whereas baseline plasma MPO levels did
      not differ between patients with or without angiographically detectable coronary
      artery disease (CAD), the increase in MPO plasma content on bolus heparin
      administration was higher in patients with CAD (P=0.01). Heparin treatment also
      improved endothelial NO bioavailability, as evidenced by flow-mediated dilation
      (P<0.01) and by acetylcholine-induced changes in forearm blood flow (P<0.01). The
      extent of heparin-induced MPO release was correlated with improvement in
      endothelial function (r=0.69, P<0.01). Moreover, and consistent with this tenet,
      ex vivo heparin treatment of extracellular matrix proteins, cultured endothelial
      cells, and saphenous vein graft specimens from CAD patients decreased MPO burden.
      CONCLUSIONS: Mobilization of vessel-associated MPO may represent an important
      mechanism by which heparins exert antiinflammatory effects and increase vascular
      NO bioavailability. These data add to the growing body of evidence for a causal
      role of MPO in compromised vascular NO signaling in humans.

PMID- 16606793
TI  - Retrospective determination of the area at risk for reperfused acute myocardial
      infarction with T2-weighted cardiac magnetic resonance imaging: histopathological
      and displacement encoding with stimulated echoes (DENSE) functional validations.
AB  - BACKGROUND: The aim of this study was to determine whether edema imaging by T2
      weighted cardiac magnetic resonance (CMR) imaging could retrospectively delineate
      the area at risk in reperfused myocardial infarction. We hypothesized that the
      size of the area at risk during a transient occlusion would be similar to the T2
      weighted hyperintense region observed 2 days later, that the T2-weighted
      hyperintense myocardium would show partial functional recovery after 2 months,
      and that the T2 abnormality would resolve over 2 months. METHODS AND RESULTS:
      Seventeen dogs underwent a 90-minute coronary artery occlusion, followed by
      reperfusion. The area at risk, as measured with microspheres (9 animals), was
      comparable to the size of the hyperintense zone on T2-weighted images 2 days
      later (43.4+/-3.3% versus 43.0+/-3.4% of the left ventricle; P=NS), and the 2
      measures correlated (R=0.84). The infarcted zone was significantly smaller
      (23.1+/-3.7; both P<0.001). To test whether the hyperintense myocardium would
      exhibit partial functional recovery over time, 8 animals were imaged on day 2 and
      2 months later. Systolic strain was mapped with displacement encoding with
      stimulated echoes. Edema, as detected by a hyperintense zone on T2-weighted
      images, resolved, and regional radial systolic strain partially improved from
      4.9+/-0.7 to 13.1+/-1.5 (P=0.001) over 2 months. CONCLUSIONS: These findings are
      consistent with the premise that the T2 abnormality depicts the area at risk, a
      zone of reversibly and irreversibly injured myocardium associated with reperfused
      subendocardial infarctions. The persistence of postischemic edema allows T2
      weighted CMR to delineate the area at risk 2 days after reperfused myocardial
      infarction.

PMID- 16606794
TI  - Images in cardiovascular medicine. Atypical transient left ventricular ballooning
      without involvement of apical segment.

PMID- 16606795
TI  - Images in cardiovascular medicine. Coronary artery spasm.

PMID- 16606796
TI  - Images in cardiovascular medicine. Recovery of left ventricular systolic function
      after biventricular resynchronization pacing in a child with repaired tetralogy
      of Fallot and severe biventricular dysfunction.

PMID- 16606797
TI  - Letter regarding article by Imazio et al, "colchicine in addition to conventional
      therapy for acute pericarditis".

PMID- 16606798
TI  - Cachexia and cardiology.

PMID- 16606799
TI  - Dobutamine stress echocardiography in patients with low-gradient aortic stenosis.

PMID- 16606800
TI  - Understanding coronary blood flow: the wave of the future.

PMID- 16606801
TI  - Contrast-induced nephropathy: a clinical and evidence-based approach.

PMID- 16606802
TI  - Diurnal blood pressure changes in stroke subtypes.

PMID- 16606805
TI  - Aldosterone and large artery vessels.

PMID- 16606806
TI  - The role of fibrates in a statin world.

PMID- 16606807
TI  - Antiarrhythmic drugs for maintaining sinus rhythm after cardioversion of atrial
      fibrillation: a systematic review of randomized controlled trials.
AB  - BACKGROUND: A variety of antiarrhythmic drugs have been used to prevent
      recurrence of atrial fibrillation after conversion to sinus rhythm. We performed
      a systematic review to determine the effect of long-term treatment with those
      drugs on death, embolisms, adverse effects, and atrial fibrillation recurrence.
      METHODS: We searched MEDLINE, EMBASE, the Cochrane Library (all up to May 2005),
      and the reference lists of retrieved articles. We included randomized controlled
      trials that compared any antiarrhythmic against control (placebo or no treatment)
      or another antiarrhythmic, for more than 6 months. Postoperative atrial
      fibrillation was excluded. Two evaluators independently reviewed the retrieved
      studies and extracted all data. Disagreements were resolved by discussion. All
      results were calculated at 1 year of follow-up. RESULTS: Forty-four trials were
      included, with a total of 11 322 patients. Several class IA (disopyramide
      phosphate, quinidine sulfate), class IC (flecainide acetate, propafenone
      hydrochloride), and class III (amiodarone, dofetilide, sotalol hydrochloride)
      drugs significantly reduced recurrence of atrial fibrillation (number needed to
      treat, 2-9), but all increased withdrawals due to adverse effects (number needed
      to harm [NNH], 9-27) and all but amiodarone and propafenone increased
      proarrhythmia (NNH, 17-119). Class IA drugs, pooled, were associated with
      increased mortality compared with controls (Peto odds ratio, 2.39; 95% confidence
      interval, 1.03-5.59; P = .04; NNH, 109). No other antiarrhythmic showed a
      significant effect on mortality compared with controls. We could not analyze
      other outcomes because data were lacking. CONCLUSION: Class IA, IC, and III drugs
      are effective in maintaining sinus rhythm but increase adverse effects, and class
      IA drugs may increase mortality.

PMID- 16606808
TI  - Risk of recurrent venous thromboembolism in patients with common thrombophilia: a
      systematic review.
AB  - The 2 most common genetic polymorphisms that predispose to a first episode of
      venous thromboembolism (VTE) are factor V Leiden (FVL) and prothrombin G20210A.
      However, the effect of these polymorphisms on the risk of recurrent VTE is
      unclear. We performed a meta-analysis to obtain best estimates of the relative
      risk of recurrent VTE associated with these genetic polymorphisms. Electronic and
      manual searches were used to identify cohort studies of patients with a first
      episode of VTE that reported the incidence of objectively confirmed recurrence
      following discontinuation of anticoagulation among those with or without
      heterozygous FVL or prothrombin G20210A polymorphism. Thirteen reports fulfilled
      our criteria for inclusion. Pooled results from 10 studies involving 3104
      patients with first-ever VTE revealed that FVL was present in 21.4% of patients
      (95% confidence interval [CI], 20%-23%) and associated with an increased odds of
      recurrent VTE of 1.41 (95% CI, 1.14-1.75; P = .08 for heterogeneity). Pooled
      results from 9 studies involving 2903 patients with first-ever VTE revealed that
      prothrombin G20210A was present in 9.7% of patients (95% CI, 9%-11%) and
      associated with an increased odds of recurrent VTE of 1.72 (95% CI, 1.27-2.31; P
      = .19). The estimated population-attributable risk of recurrence for FVL was 9.0%
      (95% CI, 4.5%-13.2%) and for prothrombin G20210A was 6.7% (95% CI, 3.4%-9.9%).
      Heterozygous FVL and prothrombin G20210A are each associated with a significantly
      increased risk of recurrent VTE after a first event, but the magnitude of the
      increase in risk is modest and by itself is unlikely to merit extended-duration
      anticoagulation. These data call into question the cost-effectiveness of routine
      testing for these common inherited thrombophilic polymorphisms among patients
      with a first episode of VTE.

PMID- 16606809
TI  - Attenuation of progression of insulin resistance in patients with coronary artery
      disease by bezafibrate.
AB  - BACKGROUND: Development of insulin resistance (IR) may be important in the
      pathogenesis of both metabolic syndrome and type 2 diabetes mellitus. Few data
      are available regarding the short-term efficacy of the peroxisome proliferator
      activated receptor ligand bezafibrate on IR, and its long-term effect is unknown.
      The present analysis aimed to investigate the effect of bezafibrate on IR in
      patients with coronary artery disease enrolled in the Bezafibrate Infarction
      Prevention Study. METHODS: Metabolic and inflammatory parameters were analyzed
      from stored frozen plasma samples obtained from patients who completed a 2-year,
      randomized, double-blind, placebo-controlled study. The homeostatic indexes of IR
      (HOMA-IRs) were calculated according to the homeostasis model of assessment.
      RESULTS: Both the patients taking bezafibrate (n = 1262) and those taking placebo
      (n = 1242) displayed similar baseline characteristics. The HOMA-IRs significantly
      correlated at baseline and during follow-up with glucose (r = 0.35 and 0.31,
      respectively) and triglycerides (r = 0.16 and 0.19, respectively). In a subgroup
      of 351 patients with diabetes, HOMA-IR at baseline was 88% higher than in their
      counterparts with normal glucose levels (P<.001). In the placebo group, during
      follow-up there was a significant 34.4% rise in HOMA-IR. In contrast, in the
      bezafibrate group there was only a nonsignificant 6.6% change in HOMA-IR. The
      intergroup differences in percentage changes of HOMA-IR were in favor of
      bezafibrate (P<.001). CONCLUSIONS: In patients with coronary artery disease
      enrolled in our study, as represented by the placebo group, HOMA-IR increased
      over time. During the 2 years of the follow-up, bezafibrate significantly
      attenuated this process.

PMID- 16606810
TI  - Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of
      the Helsinki Heart Study.
AB  - BACKGROUND: The Helsinki Heart Study was a double-blind, placebo-controlled
      primary prevention trial among 4081 dyslipidemic middle-aged men to test the
      efficacy of gemfibrozil in the prevention of coronary heart disease (CHD). After
      the 5-year trial, the participants were notified of their treatment group and
      invited to continue or start gemfibrozil therapy free of charge through 1995.
      Approximately two thirds of participants in both groups chose gemfibrozil
      therapy. In this 18-year follow-up through 2000, we compared the CHD, cancer, and
      all-cause mortality among subjects in the original gemfibrozil (OG) group (n =
      2046) with those in the original placebo (OP) group (n = 2035). METHODS: To
      provide an overview of the absolute risks in the 2 treatment groups as well as
      risk differences between them, we calculated crude mortality rates and presented
      Kaplan-Meier plots of survival with log-rank tests. We also estimated the
      relative risks (RRs) using Cox proportional hazards models with and without
      covariates. RESULTS: During the follow-up until 1995, subjects in the OG group
      had a 32% lower RR of CHD mortality (P = .03) compared with those in the OP
      group, and when followed up until 2000, the RR was 23% lower (P = .05). Overall,
      there were no differences in all-cause or cancer mortality. However, those in the
      OG group with both body mass index and triglyceride level in the highest tertiles
      had a 71% lower RR of CHD mortality (P<.001), a 33% lower RR of all-cause
      mortality (P = .03), and a 36% lower RR of cancer mortality (P = .22) compared
      with those in the OP group. CONCLUSION: Long-term mortality follow-up showed that
      patients with dyslipidemia benefited from beginning treatment with gemfibrozil
      early, especially if their dyslipidemia entailed factors related to the metabolic
      syndrome.

PMID- 16606811
TI  - Terminal sedation and euthanasia: a comparison of clinical practices.
AB  - BACKGROUND: An important issue in the debate about terminal sedation is the
      extent to which it differs from euthanasia. We studied clinical differences and
      similarities between both practices in the Netherlands. METHODS: Personal
      interviews were held with a nationwide stratified sample of 410 physicians
      (response rate, 85%) about the most recent cases in which they used terminal
      sedation, defined as administering drugs to keep the patient continuously in deep
      sedation or coma until death without giving artificial nutrition or hydration (n
      = 211), or performed euthanasia, defined as administering a lethal drug at the
      request of a patient with the explicit intention to hasten death (n = 123). We
      compared characteristics of the patients, the decision-making process, and
      medical care of both practices. RESULTS: Terminal sedation and euthanasia both
      mostly concerned patients with cancer. Patients receiving terminal sedation were
      more often anxious (37%) and confused (24%) than patients receiving euthanasia
      (15% and 2%, respectively). Euthanasia requests were typically related to loss of
      dignity and a sense of suffering without improving, whereas requesting terminal
      sedation was more often related to severe pain. Physicians applying terminal
      sedation estimated that the patient's life had been shortened by more than 1 week
      in 27% of cases, compared with 73% in euthanasia cases. CONCLUSIONS: Terminal
      sedation and euthanasia both are often applied to address severe suffering in
      terminally ill patients. However, terminal sedation is typically used to address
      severe physical and psychological suffering in dying patients, whereas perceived
      loss of dignity during the last phase of life is a major problem for patients
      requesting euthanasia.

PMID- 16606812
TI  - Adoption of patient-centered care practices by physicians: results from a
      national survey.
AB  - BACKGROUND: Little is known about the extent to which primary care physicians
      (PCPs) practice patient-centered care, 1 of the Institute of Medicine's 6
      dimensions of quality. This article describes the adoption of patient-centered
      practice attributes by PCPs. METHODS: Mail survey; nationally representative
      physician sample of 1837 physicians in practice at least 3 years postresidency.
      RESULTS: Eighty-three percent of PCPs surveyed are in favor of sharing of medical
      records with patients. Most physicians (87%) support team-based care. But, only
      16% of PCPs communicate with their patients via e-mail; only 36% get feedback
      from their patients. Seventy-four percent of PCPs still experience problems with
      availability of patients' medical records or test results; less than 50% have
      adopted patient reminder systems. Thirty-three percent of physicians practicing
      in groups of 50 or more have adopted 6 to 11 of the 11 patient-centered care
      practices targeted in the survey compared with 14% of solo physicians.
      CONCLUSION: Although some patient-centered care practices have been adopted by
      most PCPs, other practices have not yet been adopted as broadly, especially those
      targeting coordination, team-based care, and support from appropriate information
      systems.

PMID- 16606813
TI  - A prospective study of female hormone use and breast cancer among black women.
AB  - BACKGROUND: Epidemiologic studies, largely of white women, have found that recent
      long-term female hormone use, particularly use of estrogen with progestin, is
      associated with an increased risk of breast cancer. Some studies suggest that the
      increase is greater among leaner women. Our aim was to assess the relation of
      female hormone use to incidence of breast cancer in black women, with attention
      to differences in effect according to body mass index. METHODS: Data on female
      hormone use, breast cancer risk factors, and the occurrence of breast cancer were
      collected through biennial questionnaires from 1995 through 2003 in the Black
      Women's Health Study, a follow-up study of US black women. During 182 629 person
      years of follow-up of 32 559 women 40 years or older, 615 cases of breast cancer
      were reported. RESULTS: The incidence rate ratio for breast cancer in women
      recently using female hormone supplements relative to those who had never used
      female hormones, with control for confounding factors, increased with duration of
      use and was 1.58 (95% confidence interval [CI], 1.12-2.23) for 10 or more years
      of use; the incidence rate ratios were 1.41 (95% CI, 0.95-2.10) for 10 or more
      years of use of estrogen alone, and 1.45 (95% CI, 0.94-2.23) for 5 or more years
      of use of estrogen with progestin. The association of breast cancer with female
      hormone use was stronger among leaner women (body mass index [calculated as
      weight in kilograms divided by the square of height in meters] <25) than among
      heavier women. Among the leaner women who recently used female hormone
      supplements for durations of 10 or more years, the incidence rate ratio was 3.08
      (95% CI, 1.70-5.56); the corresponding estimates among women with body mass
      indexes of 25 to 29 and 30 or greater were 1.43 and 0.91, respectively, and
      neither was statistically significant. CONCLUSION: These results based on data
      from US black women strengthen the evidence that use of estrogen alone and
      estrogen with progestin increases the risk of breast cancer and that the
      association is stronger among leaner women.

PMID- 16606814
TI  - Early ambulation after hip fracture: effects on function and mortality.
AB  - BACKGROUND: Few studies have examined the relationship between inpatient bed rest
      and functional outcomes. We examined how immobility is associated with function
      and mortality in patients with hip fracture. METHODS: We conducted a prospective
      cohort study of 532 patients 50 years and older, who were treated with surgery
      after hip fracture in 4 hospitals in New York. We collected information from
      hospital visits, medical records, and interviews. "Days of immobility" was
      defined as days until the patient moved out of bed beyond a chair. Follow-up was
      obtained on function (using the Functional Independence Measure) at 2 and 6
      months and on survival at 6 months. RESULTS: Patients with hip fracture
      experienced an average of 5.2 days of immobility. Compared with patients with a
      longer duration of immobility (ie, at the 90th percentile) in adjusted analyses,
      patients at the 10th percentile of immobility had lower 6-month mortality (-5.4%;
      95% confidence interval [CI], -10.9% to -1.0%) and better Functional Independence
      Measure score for locomotion (0.99 points; 95% CI, 0.3 to 1.7 points, with higher
      values indicating better function), but there was no significant difference in
      locomotion by 6 months (0.58 points; 95% CI, -0.3 to 1.4 points). The adverse
      association of immobility was strongest in patients using personal assistance or
      supervision with locomotion at baseline (difference in 6-month mortality between
      the 90th and 10th percentile of immobility was -17.1% [P = .004] for this group
      and only 1.2% [P = .38] for patients independent in locomotion at baseline).
      CONCLUSION: In patients with hip fracture, delay in getting the patient out of
      bed is associated with poor function at 2 months and worsened 6-month survival.

PMID- 16606815
TI  - Venous thrombosis and conjugated equine estrogen in women without a uterus.
AB  - BACKGROUND: Postmenopausal hormone therapy has been associated with a 2- to 3
      fold increased risk of venous thromboembolism (VT) (including deep vein
      thrombosis and pulmonary embolism) in observational studies and secondary
      prevention clinical trials. Clinical trial data on the effects of estrogen alone
      on VT are limited. METHODS: The Women's Health Initiative estrogen trial enrolled
      10 739 women aged 50 to 79 years without a uterus. Participants were randomly
      assigned to receive conjugated equine estrogen (0.625 mg/d) or placebo. RESULTS:
      During a mean of 7.1 years, VT occurred in 111 women randomly assigned to receive
      estrogen (3.0 per 1000 person-years) and 86 randomly assigned to receive placebo
      (2.2 per 1000 person-years; hazard ratio, 1.32; 95% confidence interval, 0.99
      1.75). Deep venous thrombosis was reported in 85 women randomly assigned to
      receive estrogen (2.3 per 1000 person-years) and 59 randomly assigned to receive
      placebo (1.5 per 1000 person-years; hazard ratio, 1.47; 95% confidence interval,
      1.06-2.06). The VT risk was highest in the first 2 years. There were no
      significant interactions between estrogen use and age, body mass index, or most
      other VT risk factors. Comparison of Women's Health Initiative VT findings for
      estrogen and previous Women's Health Initiative findings for estrogen plus
      progestin showed that the hazard ratios for estrogen plus progestin were
      significantly higher than those for estrogen alone (P = .03), even after
      adjusting for VT risk factors. CONCLUSION: An early increased VT risk is
      associated with use of estrogen, especially within the first 2 years, but this
      risk increase is less than that for estrogen plus progestin.

PMID- 16606816
TI  - Hyponatremia and long-term mortality in survivors of acute ST-elevation
      myocardial infarction.
AB  - BACKGROUND: Hyponatremia, a marker of neurohormonal activation, is a common
      electrolyte disorder among patients with acute ST-elevation myocardial
      infarction. The long-term prognostic value of hyponatremia during the acute phase
      of infarction is not known. METHODS: We studied 978 patients with acute ST
      elevation myocardial infarction and without a history of heart failure who
      survived the index event. During the hospital stay, sodium levels were obtained
      on admission and at 24, 48, and 72 hours. The median duration of follow-up after
      hospital discharge was 31 months (range, 9-61 months). RESULTS: Hyponatremia,
      defined as a mean serum sodium level less than 136 mEq/L, was present during
      admission in 108 patients (11.0%). In a multivariable Cox proportional hazards
      model adjusting for other potential clinical predictors of mortality and for left
      ventricular ejection fraction, hyponatremia during admission remained an
      independent predictor of postdischarge death (hazard ratio [HR], 2.0; 95%
      confidence interval [CI], 1.3-3.2; P = .002). Hyponatremia during admission was
      also independently associated with postdischarge readmission for heart failure
      (HR, 1.6; 95% CI, 1.1-2.6; P = .04). When serum sodium level was used as a
      continuous variable, the adjusted HR for death or heart failure was 1.12 for
      every 1-mEq/L decrease (95% CI, 1.07-1.18; P<.001). CONCLUSION: Hyponatremia in
      the early phase of ST-elevation myocardial infarction is a predictor of long-term
      mortality and admission for heart failure after hospital discharge, independent
      of other clinical predictors of adverse outcome and left ventricular ejection
      fraction.

PMID- 16606817
TI  - Angiotensin-converting enzyme inhibitors in patients with coronary artery disease
      and absence of heart failure or left ventricular systolic dysfunction: an
      overview of long-term randomized controlled trials.
AB  - BACKGROUND: Results of randomized trials of angiotensin-converting enzyme
      inhibitors in patients with coronary artery disease (CAD) and preserved left
      ventricular function are conflicting. We undertook this study to determine
      whether long-term prescription of angiotensin-converting enzyme inhibitors
      decreases major cardiovascular events and mortality in patients who have CAD and
      no evidence of left ventricular systolic dysfunction. METHODS: We searched
      MEDLINE, EMBASE, and IPA databases, the Cochrane Controlled Trials Register (1990
      2004), and reports from scientific meetings (2003-2004), and we reviewed
      secondary sources. Search terms included angiotensin-converting enzyme
      inhibitors, coronary artery disease, randomi(s)zed controlled trials, clinical
      trials, and myocardial infarction. Eligible studies included randomized
      controlled trials in patients who had CAD and no heart failure or left
      ventricular dysfunction, with follow-up omicronf 2 years or longer. Of 1146
      publications screened, 7 met our selection criteria and included a total of 33
      960 patients followed up for a mean of 4.4 years. RESULTS: Five trials included
      only patients with documented CAD. One trial included patients with documented
      CAD (80%) or patients who had diabetes mellitus and 1 or more additional risk
      factors, and another trial included patients who had CAD, a history of transient
      ischemic attack, or intermittent claudication. Treatment with angiotensin
      converting enzyme inhibitors decreased overall mortality (odds ratio, 0.86; 95%
      confidence interval, 0.79-0.93), cardiovascular mortality (odds ratio, 0.81; 95%
      confidence interval, 0.73-0.90), myocardial infarction (odds ratio, 0.82; 95%
      confidence interval, 0.75-0.89), and stroke (odds ratio, 0.77; 95% confidence
      interval, 0.66-0.88). Other end points, including resuscitation after cardiac
      arrest, myocardial revascularization, and hospitalization because of heart
      failure, were also reduced. CONCLUSION: Angiotensin-converting enzyme inhibitors
      reduce total mortality and major cardiovascular end points in patients who have
      CAD and no left ventricular systolic dysfunction or heart failure.

PMID- 16606818
TI  - Differing effects of antihypertensive drugs on the incidence of diabetes mellitus
      among patients with hypertensive kidney disease.
AB  - BACKGROUND: The African American Study of Kidney Disease and Hypertension was a
      multicenter trial of African Americans with hypertensive kidney disease
      randomized to an angiotensin-converting enzyme inhibitor (ramipril), a beta
      blocker (metoprolol succinate), or a calcium channel blocker (amlodipine
      besylate). We compared the incidence of type 2 diabetes mellitus (DM) and the
      composite outcome of impaired fasting glucose or DM (IFG/DM) for the African
      American Study of Kidney Disease and Hypertension interventions. METHODS: Cox
      regression models were used to evaluate (post hoc) the association of the
      randomized interventions and the relative risk (RR) of DM and IFG/DM and to
      assess the RR of DM and IFG/DM by several prerandomization characteristics.
      RESULTS: Among 1017 participants, 147 (14.5%) developed DM; 333 (42.9%) of 776
      participants developed IFG/DM. Respective DM event rates were 2.8%, 4.4%, and
      4.5% per patient-year in the ramipril-, amlodipine-, and metoprolol-treated
      groups. The RRs of DM with ramipril treatment were 0.53 (P = .001) compared with
      metoprolol treatment and 0.49 (P = .003) compared with amlodipine treatment.
      Respective IFG/DM event rates were 11.3%, 13.3%, and 15.8% per patient-year in
      the ramipril-, amlodipine-, and metoprolol-treated groups. The RRs of IFG/DM with
      ramipril treatment were 0.64 (P<.001) compared with metoprolol treatment and 0.76
      (P = .09) compared with amlodipine treatment. The RRs of DM and IFG/DM with
      amlodipine treatment compared with metoprolol treatment were 1.07 (P = .76) and
      0.84 (P = .26), respectively. CONCLUSION: Ramipril treatment was associated with
      a significantly lower risk of DM in African Americans with hypertensive kidney
      disease than amlodipine or metoprolol treatment.

PMID- 16606819
TI  - Clopidogrel to treat patients with non-ST-segment elevation acute coronary
      syndromes after hospital discharge.
AB  - BACKGROUND: Clopidogrel added to aspirin improved outcomes after hospitalization
      in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) in
      the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial,
      regardless of in-hospital treatment approach. The American College of
      Cardiology/American Heart Association (ACC/AHA) Guidelines for treating NSTE ACS
      thus recommend prescribing clopidogrel plus aspirin at discharge for all
      patients, not just for those undergoing percutaneous coronary intervention (PCI).
      METHODS: We studied 61 052 patients with high-risk NSTE ACS (defined as the
      presence of positive cardiac markers and/or ischemic ST-segment changes) from
      January 2002 through December 2003 at 461 US hospitals participating in the
      CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress
      Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) Quality
      Improvement Initiative. We evaluated temporal trends of clopidogrel use at
      discharge since the ACC/AHA 2002 Guidelines update and examined variables
      associated with clopidogrel use in patients who did not undergo PCI. RESULTS: A
      total of 34 319 patients (56.2%) received clopidogrel when they were discharged
      from the hospital. Among patients who did not undergo PCI, variables associated
      with receiving clopidogrel at discharge included prior PCI, coronary artery
      bypass grafting (CABG), stroke, or myocardial infarction; hypercholesterolemia;
      elevated cardiac markers; and cardiology inpatient care. By late 2003, 96.3% of
      patients who underwent PCI received clopidogrel at discharge, compared with 42.8%
      of patients who did not undergo cardiac catheterization and 23.5% of the patients
      who underwent CABG, although clopidogrel prescription at discharge increased in
      each of these treatment groups from 2002 to 2003. CONCLUSION: Since release of
      the ACC/AHA Guidelines recommendations for treatment of NSTE ACS, prescription of
      clopidogrel at hospital discharge in patients with NSTE ACS who are treated with
      medical therapy alone and in those who undergo CABG has increased, but most of
      these patients still do not receive clopidogrel at discharge.

PMID- 16606820
TI  - Action on racial disparity in hypertension control.

PMID- 16606821
TI  - Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol
      homeostasis.
AB  - Insig-1 and Insig-2 are closely related proteins of the endoplasmic reticulum
      (ER) that mediate feedback control of cholesterol synthesis by sterol-dependent
      binding to the following two membrane proteins: the escort protein Scap, thus
      preventing proteolytic processing of sterol regulatory element-binding proteins;
      and the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl CoA reductase,
      thus inducing the ubiquitination and ER-associated degradation of the enzyme.
      Here, we report that the conserved Asp-205 in Insig-1, which abuts the fourth
      transmembrane helix at the cytosolic side of the ER membrane, is essential for
      its dual function. When Asp-205 was mutated to alanine, the mutant Insig-1 lost
      the ability to bind to Scap and, thus, was unable to suppress the cleavage of
      sterol regulatory element-binding proteins. The mutant Insig-1 was ineffective
      also in accelerating sterol-stimulated degradation of 3-hydroxy-3-methylglutaryl
      CoA reductase. Alanine substitution of the corresponding aspartic acid in Insig-2
      produced the same dual defects. These studies identify a single amino acid
      residue that is crucial for the function of Insig proteins in regulating
      cholesterol homeostasis in mammalian cells.

PMID- 16606822
TI  - Multiple sclerosis may disrupt endocannabinoid brain protection mechanism.

PMID- 16606823
TI  - Partnering between monomers of cyclooxygenase-2 homodimers.
AB  - Prostaglandin endoperoxide H synthases (PGHSs) 1 and 2 convert arachidonic acid
      to prostaglandin H2 in the committed step of prostanoid biosynthesis. These
      enzymes are pharmacological targets of nonsteroidal antiinflammatory drugs and
      cyclooxygenase (COX) 2 inhibitors. Although PGHSs function as homodimers and each
      monomer has its own COX and peroxidase active sites, the question of whether
      there is cross-talk between monomers has remained unresolved. Here we describe
      two heterodimers in which a native subunit of human PGHS-2 has been coupled to a
      subunit having a defect within the COX active site at some distance from the
      dimer interface. Native/G533A PGHS-2, a heterodimer with a COX-inactive subunit,
      had the same specific COX activity as the native homodimer. Native/R120Q PGHS-2,
      a heterodimer in which both subunits can oxygenate arachidonic acid but in which
      the R120Q subunit cannot bind the COX inhibitor flurbiprofen, was inhibited by
      flurbiprofen to about the same extent as native PGHS-2. These results imply that
      native PGHS-2 exhibits half-of-sites reactivity. Isothermal titration calorimetry
      established that only one monomer of the native PGHS-2 homodimer binds
      flurbiprofen tightly. In short, binding of ligand to the COX site of one monomer
      alters its companion monomer so that it is unable to bind substrate or inhibitor.
      We conclude that PGHS monomers comprising a dimer, although identical in the
      resting enzyme, differ from one another during catalysis. The nonfunctioning
      subunit may provide structural support enabling its partner monomer to catalyze
      the COX reaction. This subunit complementarity may prove to be characteristic of
      other dimeric enzymes having tightly associated monomers.

PMID- 16606824
TI  - Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo.
AB  - Targeted uptake of therapeutic nanoparticles in a cell-, tissue-, or disease
      specific manner represents a potentially powerful technology. Using prostate
      cancer as a model, we report docetaxel (Dtxl)-encapsulated nanoparticles
      formulated with biocompatible and biodegradable poly(D,L-lactic-co-glycolic acid)
      block-poly(ethylene glycol) (PLGA-b-PEG) copolymer and surface functionalized
      with the A10 2'-fluoropyrimidine RNA aptamers that recognize the extracellular
      domain of the prostate-specific membrane antigen (PSMA), a well characterized
      antigen expressed on the surface of prostate cancer cells. These Dtxl
      encapsulated nanoparticle-aptamer bioconjugates (Dtxl-NP-Apt) bind to the PSMA
      protein expressed on the surface of LNCaP prostate epithelial cells and get taken
      up by these cells resulting in significantly enhanced in vitro cellular toxicity
      as compared with nontargeted nanoparticles that lack the PSMA aptamer (Dtxl-NP)
      (P < 0.0004). The Dtxl-NP-Apt bioconjugates also exhibit remarkable efficacy and
      reduced toxicity as measured by mean body weight loss (BWL) in vivo [body weight
      loss of 7.7 +/- 4% vs. 18 +/- 5% for Dtxl-NP-Apt vs. Dtxl-NP at nadir,
      respectively (mean +/- SD); n = 7]. After a single intratumoral injection of Dtxl
      NP-Apt bioconjugates, complete tumor reduction was observed in five of seven
      LNCaP xenograft nude mice (initial tumor volume of approximately 300 mm3), and
      100% of these animals survived our 109-day study. In contrast, two of seven mice
      in the Dtxl-NP group had complete tumor reduction with 109-day survivability of
      only 57%. Dtxl alone had a survivability of only 14%. Saline and nanoparticles
      without drug were similarly nonefficacious. This report demonstrates the
      potential utility of nanoparticle-aptamer bioconjugates for a therapeutic
      application.

PMID- 16606825
TI  - Nanoindentation studies of full and empty viral capsids and the effects of capsid
      protein mutations on elasticity and strength.
AB  - The elastic properties of capsids of the cowpea chlorotic mottle virus have been
      examined at pH 4.8 by nanoindentation measurements with an atomic force
      microscope. Studies have been carried out on WT capsids, both empty and
      containing the RNA genome, and on full capsids of a salt-stable mutant and empty
      capsids of the subE mutant. Full capsids resisted indentation more than empty
      capsids, but all of the capsids were highly elastic. There was an initial
      reversible linear regime that persisted up to indentations varying between 20%
      and 30% of the diameter and applied forces of 0.6-1.0 nN; it was followed by a
      steep drop in force that is associated with irreversible deformation. A single
      point mutation in the capsid protein increased the capsid stiffness. The
      experiments are compared with calculations by finite element analysis of the
      deformation of a homogeneous elastic thick shell. These calculations capture the
      features of the reversible indentation region and allow Young's moduli and
      relative strengths to be estimated for the empty capsids.

PMID- 16606826
TI  - Impaired neurogenesis and cardiovascular development in mice lacking the E3
      ubiquitin ligases UBR1 and UBR2 of the N-end rule pathway.
AB  - The N-end rule relates the in vivo half-life of a protein to the identity of its
      N-terminal residue. A subset of degradation signals recognized by the N-end rule
      pathway comprises the signals, called N-degrons, whose determinants include
      destabilizing N-terminal residues. Our previous work identified a family of at
      least four mammalian E3 ubiquitin ligases, including UBR1 and UBR2, that share
      the UBR box and recognize N-degrons. These E3 enzymes mediate the multifunctional
      N-end rule pathway, but their individual roles are just beginning to emerge.
      Mutations of UBR1 in humans are the cause of Johanson-Blizzard syndrome. UBR1 and
      UBR2 are 46% identical and appear to be indistinguishable in their recognition of
      N-degrons. UBR1-/- mice are viable but have defects that include pancreatic
      insufficiency, similarly to UBR1-/- human patients with Johanson-Blizzard
      syndrome. UBR2-/- mice are inviable in some strain backgrounds and are defective
      in male meiosis. To examine functional relationships between UBR1 and UBR2, we
      constructed mouse strains lacking both of these E3s. We report here that UBR1-/
      UBR2-/- embryos die at midgestation, with defects in neurogenesis and
      cardiovascular development. These defects included reduced proliferation as well
      as precocious migration and differentiation of neural progenitor cells. The
      expression of regulators such as D-type cyclins and Notch1 was also altered in
      UBR1-/-UBR2-/- embryos. We conclude that the functions of UBR1 and UBR2 are
      significantly divergent, in part because of differences in their expression
      patterns and possibly also because of differences in their recognition of protein
      substrates that contain degradation signals other than N-degrons.

PMID- 16606827
TI  - The tomato FT ortholog triggers systemic signals that regulate growth and
      flowering and substitute for diverse environmental stimuli.
AB  - The systemic model for floral induction, dubbed florigen, was conceived in
      photoperiod-sensitive plants but implies, in its ultimate form, a graft
      transmissible signal that, although activated by different stimuli in different
      flowering systems, is common to all plants. We show that SFT (SINGLE-FLOWER
      TRUSS), the tomato ortholog of FLOWERING LOCUS T (FT), induces flowering in day
      neutral tomato and tobacco plants and is encoded by SFT. sft tomato mutant plants
      are late-flowering, with altered architecture and flower morphology. SFT
      dependent graft-transmissible signals complement all developmental defects in sft
      plants and substitute for long-day stimuli in Arabidopsis, short-day stimuli in
      Maryland Mammoth tobacco, and light-dose requirements in tomato uniflora mutant
      plants. The absence of donor SFT RNA from flowering receptor shoots and the
      localization of the protein in leaf nuclei implicate florigen-like messages in
      tomato as a downstream pathway triggered by cell-autonomous SFT RNA transcripts.
      Flowering in tomato is synonymous with termination of the shoot apical meristems,
      and systemic SFT messages attenuate the growth of apical meristems before and
      independent of floral production. Floral enhancement by systemic SFT signals is
      therefore one pleiotropic effect of FT orthologs.

PMID- 16606828
TI  - The mechanism of M.HhaI DNA C5 cytosine methyltransferase enzyme: a quantum
      mechanics/molecular mechanics approach.
AB  - The mechanism of DNA cytosine-5-methylation catalyzed by the bacterial M.HhaI
      enzyme has been considered as a stepwise nucleophilic addition of Cys-81-S- to
      cytosine C6 followed by C5 nucleophilic replacement of the methyl of S-adenosyl-L
      methionine to produce 5-methyl-6-Cys-81-S-5,6-dihydrocytosine. In this study, we
      show that the reaction is concerted from a series of energy calculations by using
      the quantum mechanical/molecular mechanical hybrid method. Deprotonation of 5
      methyl-6-Cys-81-S-5,6-dihydrocytosine and expulsion of Cys-81-S- provides the
      product DNA 5-methylcytosine. A required base catalyst for this deprotonation is
      not available as a member of the active site structure. A water channel between
      the active site and bulk water allows entrance of solvent to the active site.
      Hydroxide at 10(-7) mole fraction (pH = 7) is shown to be sufficient for the
      required catalysis. We also show that Glu-119-CO2H can divert the reaction by
      protonating cytosine N3 when Cys-81-S- attacks cytosine, to form the 6-Cys-81-S-3
      hydrocytosine. The reactants and 6-Cys-81-S-3-hydrocytosine product are in rapid
      equilibrium, and this explains the observed hydrogen exchange of cytosine with
      solvent.

PMID- 16606829
TI  - An impending water crisis in Canada's western prairie provinces.
AB  - Canada is usually considered to be a country with abundant freshwater, but in its
      western prairie provinces (WPP), an area 1/5 the size of Europe, freshwater is
      scarce. European settlement of the WPP did not begin until the late 19th and
      early 20th centuries. Fortuitously, the period since European settlement appears
      to have been the wettest century of the past two millennia. The frequent, long
      periods of drought that characterized earlier centuries of the past two millennia
      were largely absent in the 20th century. Here, we show that climate warming and
      human modifications to catchments have already significantly reduced the flows of
      major rivers of the WPP during the summer months, when human demand and in-stream
      flow needs are greatest. We predict that in the near future climate warming, via
      its effects on glaciers, snowpacks, and evaporation, will combine with cyclic
      drought and rapidly increasing human activity in the WPP to cause a crisis in
      water quantity and quality with far-reaching implications.

PMID- 16606830
TI  - Activation and repolarization of the normal human heart under complete
      physiological conditions.
AB  - Knowledge of normal human cardiac excitation stems from isolated heart or
      intraoperative mapping studies under nonphysiological conditions. Here, we use a
      noninvasive imaging modality (electrocardiographic imaging) to study normal
      activation and repolarization in intact unanesthetized healthy adults under
      complete physiological conditions. Epicardial potentials, electrograms, and
      isochrones were noninvasively reconstructed. The normal electrophysiological
      sequence during activation and repolarization was imaged in seven healthy
      subjects (four males and three females). Electrocardiographic imaging depicted
      salient features of normal ventricular activation, including timing and location
      of the earliest right ventricular (RV) epicardial breakthrough in the anterior
      paraseptal region, subsequent RV and left ventricular (LV) breakthroughs, apex-to
      base activation of posterior LV, and late activation of LV base or RV outflow
      tract. The repolarization sequence was unaffected by the activation sequence,
      supporting the hypothesis that in normal hearts, local action potential duration
      (APD) determines local repolarization time. Mean activation recovery interval
      (ARI), reflecting local APD, was in the typical human APD range (235 ms). Mean LV
      apex-to-base ARI dispersion was 42 ms. Average LV ARI exceeded RV ARI by 32 ms.
      Atrial images showed activation spreading from the sinus node to the rest of the
      atria, ending at the left atrial appendage. This study provides previously
      undescribed characterization of human cardiac activation and repolarization under
      normal physiological conditions. A common sequence of activation was identified,
      with interindividual differences in specific patterns. The repolarization
      sequence was determined by local repolarization properties rather than by the
      activation sequence, and significant dispersion of repolarization was observed
      between RV and LV and from apex to base.

PMID- 16606831
TI  - Toll-like receptor 4 plays a crucial role in the immune-adrenal response to
      systemic inflammatory response syndrome.
AB  - Sepsis and septic shock are leading killers in the noncoronary intensive care
      unit, and they remain worldwide health concerns. The initial host defense against
      bacterial infections involves Toll-like receptors (TLRs), which detect and
      respond to microbial ligands. In addition, a coordinated response of the adrenal
      and immune systems is crucial for survival during severe inflammation.
      Previously, we demonstrated a link between the innate immune system and the
      endocrine stress response involving TLR-2. Like TLR-2, TLR-4 is also expressed in
      human and mouse adrenals. In the present work, by using a low dose of LPS to
      mimic systemic inflammatory response syndrome, we have revealed marked cellular
      alterations in adrenocortical tissue and an impaired adrenal corticosterone
      response in TLR-4-/- mice. Our findings demonstrate that TLR-4 is a key mediator
      in the crosstalks between the innate immune system and the endocrine stress
      response. Furthermore, TLR polymorphisms could contribute to the underlying
      mechanisms of impaired adrenal stress response in patients with bacterial sepsis.

PMID- 16606832
TI  - CD24 is expressed by myofiber synaptic nuclei and regulates synaptic
      transmission.
AB  - The genes encoding several synaptic proteins, including acetylcholine receptors,
      acetylcholinesterase, and the muscle-specific kinase, MuSK, are expressed
      selectively by a small number of myofiber nuclei positioned near the synaptic
      site. Genetic analysis of mutant mice suggests that additional genes, expressed
      selectively by synaptic nuclei, might encode muscle-derived retrograde signals
      that regulate the differentiation of motor axon terminals. To identify candidate
      retrograde signals, we used a microarray screen to identify genes that are
      preferentially expressed in the synaptic region of muscle, and we analyzed one
      such gene, CD24, further. We show that CD24, which encodes a small, variably and
      highly glycosylated, glycosylphosphatidylinositol (GPI)-linked protein, is
      expressed preferentially by myofiber synaptic nuclei in embryonic and adult
      muscle, and that CD24 expression is restricted to the central region of muscle
      independent of innervation. Moreover, we show that CD24 has a role in presynaptic
      differentiation, because synaptic transmission is depressed and fails entirely,
      in a cyclical manner, after repetitive stimulation of motor axons in CD24 mutant
      mice. These deficits in synaptic transmission, which are accompanied by aberrant
      stimulus-dependent uptake of AM1-43 from axons, indicate that CD24 is required
      for normal presynaptic maturation and function. Because CD24 is also expressed in
      some neurons, additional experiments will be required to determine whether pre-
      or postsynaptic CD24 mediates these effects on presynaptic development and
      function.

PMID- 16606833
TI  - Identification of small molecules that induce apoptosis in a Myc-dependent manner
      and inhibit Myc-driven transformation.
AB  - The Myc transcription factor plays a central role in the regulation of cell cycle
      progression, apoptosis, angiogenesis, and cellular transformation. Myc is a
      potent oncoprotein that is deregulated in a wide variety of human tumors and is
      therefore an attractive target for novel cancer therapies. Using a cellular
      screening approach, we have identified low-molecular-weight compounds, Myc
      pathway response agents (MYRAs), that induce apoptosis in a c-Myc-dependent
      manner and inhibit Myc-driven cellular transformation. MYRA-A inhibits Myc
      transactivation and interferes with the DNA-binding activity of Myc family
      proteins but has no effect on the E-box-binding protein USF. In contrast, MYRA-B
      induces Myc-dependent apoptosis without affecting Myc transactivation or Myc/Max
      DNA binding. Our data show that cellular screening assays can be a powerful
      strategy for the identification of candidate substances that modulate the Myc
      pathway. These compounds can be useful tools for studying Myc function and may
      also be of therapeutic potential as leads for drug development.

PMID- 16606834
TI  - mGluR2 acts through inhibitory Galpha subunits to regulate transmission and long
      term plasticity at hippocampal mossy fiber-CA3 synapses.
AB  - Presynaptic inhibitory G protein-coupled receptors play a critical role in
      regulating transmission at a number of synapses in the central and peripheral
      nervous system. We generated transgenic mice that express a constitutively active
      form of an inhibitory Galpha subunit to examine the molecular mechanisms
      underlying the actions of one such receptor, metabotropic glutamate receptor
      (mGluR) 2, at mossy fiber-CA3 synapses in the hippocampus. mGluR2 participates in
      at least three types of mossy fiber synaptic plasticity, (i) transient
      suppression of synaptic transmission, (ii) long-term depression (LTD), and (iii)
      inhibition of long-term potentiation (LTP), and we find that inhibitory Galpha
      signaling is sufficient to account for the actions of mGluR2 in each. The fact
      that constitutively active Galphai2 occludes the transient suppression of
      synaptic transmission by mGluR2, while enhancing LTD, suggests further that these
      two forms of plasticity are expressed via different mechanisms. In addition, the
      LTP deficit observed in constitutively active Galphai2-expressing mice suggests
      that mGluR2 activation may serve as a metaplastic switch to permit the induction
      of LTD by inhibiting LTP.

PMID- 16606835
TI  - Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate
      strongly correlated early genes in human endothelial cells.
AB  - Cysteinyl leukotrienes (cysLT), i.e., LTC4, LTD4, and LTE4, are lipid mediators
      derived from the 5-lipoxygenase pathway, and the cysLT receptors cysLT1-R/cysLT2
      R mediate inflammatory tissue reactions. Although endothelial cells (ECs)
      predominantly express cysLT2-Rs, their role in vascular biology remains to be
      fully understood. To delineate cysLT2-R actions, we stimulated human umbilical
      vein EC with LTD4 and determined early induced genes. We also compared LTD4
      effects with those induced by thrombin that binds to protease-activated receptor
      (PAR)-1. Stringent filters yielded 37 cysLT2-R- and 34 PAR-1-up-regulated genes
      (>2.5-fold stimulation). Most LTD4-regulated genes were also induced by thrombin.
      Moreover, LTD4 plus thrombin augmented gene expression when compared with each
      agonist alone. Strongly induced genes were studied in detail: Early growth
      response (EGR) and nuclear receptor subfamily 4 group A transcription factors; E
      selectin; CXC ligand 2; IL-8; a disintegrin-like and metalloprotease (reprolysin
      type) with thrombospondin type 1 motif 1 (ADAMTS1); Down syndrome critical region
      gene 1 (DSCR1); tissue factor (TF); and cyclooxygenase 2. Transcripts peaked at
      approximately 60 min, were unaffected by a cysLT1-R antagonist, and were
      superinduced by cycloheximide. The EC phenotype was markedly altered: LTD4
      induced de novo synthesis of EGR1 protein and EGR1 localized in the nucleus; LTD4
      up-regulated IL-8 formation and secretion; and LTD4 raised TF protein and TF
      dependent EC procoagulant activity. These data show that cysLT2-R activation
      results in a proinflammatory EC phenotype. Because LTD4 and thrombin are likely
      to be formed concomitantly in vivo, cysLT2-R and PAR-1 may cooperate to augment
      vascular injury.

PMID- 16606837
TI  - An astonishing 60 years: the legacy of Hiroshima.

PMID- 16606836
TI  - Mutations in fibroblast growth factor receptor 1 cause both Kallmann syndrome and
      normosmic idiopathic hypogonadotropic hypogonadism.
AB  - Mutations in KAL1 and FGFR1 cause Kallmann syndrome (KS), whereas mutations in
      the GNRHR and GPR54 genes cause idiopathic hypogonadotropic hypogonadism with
      normal olfaction (nIHH). Mixed pedigrees containing both KS and nIHH have also
      been described; however, the genetic cause of these rare cases is unknown. We
      examined the FGFR1 gene in seven nIHH subjects who either belonged to a mixed
      pedigree (n = 5) or who had associated midline defects (n = 2). Heterozygous
      FGFR1 mutations were found in three of seven unrelated nIHH probands with normal
      MRI of the olfactory system: (i) G237S in an nIHH female and a KS brother; (ii)
      (P722H and N724K) in an nIHH male missing two teeth and his mother with isolated
      hyposmia; and (iii) Q680X in a nIHH male with cleft lip/palate and missing teeth,
      his brother with nIHH, and his father with delayed puberty. We show that these
      mutations lead to receptor loss-of-function. The Q680X leads to an inactive
      FGFR1, which lacks a major portion of the tyrosine kinase domain (TKD). The G237S
      mutation inhibits proper folding of D2 of the FGFR1 and likely leads to the loss
      of cell-surface expression of FGFR1. In contrast, the (P722H and N724K) double
      mutation causes structural perturbations in TKD, reducing the catalytic activity
      of TKD. We conclude that loss-of-function mutations in FGFR1 cause nIHH with
      normal MRI of the olfactory system. These mutations also account for some of the
      mixed pedigrees, thus challenging the current idea that KS and nIHH are distinct
      entities.

PMID- 16606838
TI  - Phenotypically distinct B cell development pathways map to the three B cell
      lineages in the mouse.
AB  - A recent article by Montecino-Rodriguez et al. [Montecino-Rodriguez, E.,
      Leathers, H. & Dorshkind, K. (2006) Nat. Immunol.7, 293-301] has distinguished
      the early progenitors for B-1 cells, which principally develop in neonates, from
      early progenitors for B-2 cells, which principally develop in adult bone marrow.
      Here we introduce syndecan-1 (CD138) and MHC class II (I-A) as markers of early B
      cell development [Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D. &
      Hayakawa, K. (1991) J. Exp. Med. 173, 1213-1225; Hardy fractions B-D] and show
      that the expression of these markers distinguishes the predominant B cell
      development pathway in neonates from the corresponding predominant pathway in
      adults (both progenitors are present but differently represented in each case).
      We show that pre-B cells (Hardy fraction D) in the predominant adult pathway
      express high levels of CD138 and intermediate levels of I-A, whereas the
      corresponding pre-B cells in the pathway that predominates in neonates do not
      express either of these markers. As expected, because most of the pre-B cells in
      adults express CD138, we find that sorted CD138+ adult pre-B cells differentiate
      to IgM+ B cells in vitro. Sorted CD138- pre-B cells from neonates, the majority
      subset at this age, also mature to IgM+ cells (without passing through a CD138+
      stage). Importantly, our studies here confirm the differential representation of
      adult and neonatal progenitor populations and further demonstrate that CD138
      expression subdivides the adult CD19+, B220-6B2-/low population shown to contain
      B-1 progenitors in a way consistent with the predominance of B-1b progenitors in
      adults. Thus, CD138 expression provides a key route to distinguishing early B
      cell development pathway for what now are clearly three B cell lineages.

PMID- 16606839
TI  - Nanomechanical measurements of the sequence-dependent folding landscapes of
      single nucleic acid hairpins.
AB  - Nucleic acid hairpins provide a powerful model system for probing the formation
      of secondary structure. We report a systematic study of the kinetics and
      thermodynamics of the folding transition for individual DNA hairpins of varying
      stem length, loop length, and stem GC content. Folding was induced mechanically
      in a high-resolution optical trap using a unique force clamp arrangement with
      fast response times. We measured 20 different hairpin sequences with quasi-random
      stem sequences that were 6-30 bp long, polythymidine loops that were 3-30 nt
      long, and stem GC content that ranged from 0% to 100%. For all hairpins studied,
      folding and unfolding were characterized by a single transition. From the force
      dependence of these rates, we determined the position and height of the energy
      barrier, finding that the transition state for duplex formation involves the
      formation of 1-2 bp next to the loop. By measuring unfolding energies spanning
      one order of magnitude, transition rates covering six orders of magnitude, and
      hairpin opening distances with subnanometer precision, our results define the
      essential features of the energy landscape for folding. We find quantitative
      agreement over the entire range of measurements with a hybrid landscape model
      that combines thermodynamic nearest-neighbor free energies and nanomechanical DNA
      stretching energies.

PMID- 16606841
TI  - Resting B cells as a transfer vehicle for Epstein-Barr virus infection of
      epithelial cells.
AB  - Epstein-Barr virus (EBV), an orally transmitted herpesvirus, efficiently targets
      B lymphocytes through binding of the viral envelope glycoprotein gp350 to the
      complement receptor CD21. How the virus accesses epithelial cells is less well
      understood, because such cells are largely resistant to infection with cell-free
      virus in vitro. Here, we show that, after binding to primary B cells, most
      Epstein-Barr virions are not internalized but remain on the B cell surface and
      from there can transfer efficiently to CD21-negative epithelial cells, increasing
      epithelial infection by 10(3)- to 10(4)-fold compared with cell-free virus.
      Transfer infection is associated with the formation of B cell-epithelial
      conjugates with gp350/CD21 complexes focused at the intercellular synapse;
      transfer involves the gp85 and gp110 viral glycoproteins but is independent of
      gp42, the HLA class II ligand that is essential for B cell entry. Therefore,
      through efficient binding to the B cell surface, EBV has developed a means of
      simultaneously accessing both lymphoid and epithelial compartments; in
      particular, infection of pharyngeal epithelium by orally transmitted virus
      becomes independent of initial virus replication in the B cell system.

PMID- 16606840
TI  - Signaling mediated by the dopamine D2 receptor potentiates circadian regulation
      by CLOCK:BMAL1.
AB  - Environmental cues modulate a variety of intracellular pathways whose signaling
      is integrated by the molecular mechanism that constitutes the circadian clock.
      Although the essential gears of the circadian machinery have been elucidated,
      very little is known about the signaling systems regulating it. Here, we report
      that signaling mediated by the dopamine D2 receptor (D2R) enhances the
      transcriptional capacity of the CLOCK:BMAL1 complex. This effect involves the
      mitogen-activated protein kinase transduction cascade and is associated with a
      D2R-induced increase in the recruiting and phosphorylation of the transcriptional
      coactivator cAMP-responsive element-binding protein (CREB) binding protein.
      Importantly, CLOCK:BMAL1-dependent activation and light-inducibility of mPer1
      gene transcription is drastically dampened in retinas of D2R-null mice. Because
      dopamine is the major catecholamine in the retina, central for the neural
      adaptation to light, our findings establish a physiological link among photic
      input, dopamine signaling, and the molecular clock machinery.

PMID- 16606842
TI  - Hsp70 chaperones accelerate protein translocation and the unfolding of stable
      protein aggregates by entropic pulling.
AB  - Hsp70s are highly conserved ATPase molecular chaperones mediating the correct
      folding of de novo synthesized proteins, the translocation of proteins across
      membranes, the disassembly of some native protein oligomers, and the active
      unfolding and disassembly of stress-induced protein aggregates. Here, we bring
      thermodynamic arguments and biochemical evidences for a unifying mechanism named
      entropic pulling, based on entropy loss due to excluded-volume effects, by which
      Hsp70 molecules can convert the energy of ATP hydrolysis into a force capable of
      accelerating the local unfolding of various protein substrates and, thus, perform
      disparate cellular functions. By means of entropic pulling, individual Hsp70
      molecules can accelerate unfolding and pulling of translocating polypeptides into
      mitochondria in the absence of a molecular fulcrum, thus settling former
      contradictions between the power-stroke and the Brownian ratchet models for Hsp70
      mediated protein translocation across membranes. Moreover, in a very different
      context devoid of membrane and components of the import pore, the same physical
      principles apply to the forceful unfolding, solubilization, and assisted native
      refolding of stable protein aggregates by individual Hsp70 molecules, thus
      providing a mechanism for Hsp70-mediated protein disaggregation.

PMID- 16606843
TI  - Making the gradient: thyroid hormone regulates cone opsin expression in the
      developing mouse retina.
AB  - Most mammals have two types of cone photoreceptors, which contain either medium
      wavelength (M) or short wavelength (S) opsin. The number and spatial organization
      of cone types varies dramatically among species, presumably to fine-tune the
      retina for different visual environments. In the mouse, S- and M-opsin are
      expressed in an opposing dorsal-ventral gradient. We previously reported that
      cone opsin patterning requires thyroid hormone beta2, a nuclear hormone receptor
      that regulates transcription in conjunction with its ligand, thyroid hormone
      (TH). Here we show that exogenous TH inhibits S-opsin expression, but activates M
      opsin expression. Binding of endogenous TH to TRbeta2 is required to inhibit S
      opsin and to activate M-opsin. TH is symmetrically distributed in the retina at
      birth as S-opsin expression begins, but becomes elevated in the dorsal retina at
      the time of M-opsin onset (postnatal day 10). Our results show that TH is a
      critical regulator of both S-opsin and M-opsin, and suggest that a TH gradient
      may play a role in establishing the gradient of M-opsin. These results also
      suggest that the ratio and patterning of cone types may be determined by TH
      availability during retinal development.

PMID- 16606844
TI  - Breakpoint structure reveals the unique origin of an interspecific chromosomal
      inversion (2La) in the Anopheles gambiae complex.
AB  - Paracentric chromosomal inversions are major architects of organismal evolution
      and have been associated with adaptations relevant to malaria transmission in
      anopheline mosquitoes. The processes responsible for their origin and
      maintenance, still poorly understood, can be illuminated by analysis of inversion
      breakpoint sequences. Here, we report the breakpoint structure of chromosomal
      inversion 2La from the principal malaria vector Anopheles gambiae and its
      relatives in the A. gambiae complex. The distal and proximal breakpoints of the
      standard (2L+a) arrangement contain gene duplications: full-length genes and
      their truncated copies at opposite ends. Intact genes without pseudogene copies
      in the alternative arrangement (2La) imply that 2L+a is derived and was viable
      despite damage to genes, because duplication preserved gene function. A unique
      origin for the interspecific 2La inversion was challenged previously by indirect
      genetic evidence, but breakpoint sequences determined from members of the A.
      gambiae complex strongly suggest their descent from a single event. The derived
      position of 2L+a, long considered ancestral in this medically important group,
      has significant implications for the phylogenetic history and the evolution of
      vectorial capacity in the A. gambiae complex.

PMID- 16606845
TI  - Bone marrow-derived cells fuse with normal and transformed intestinal stem cells.
AB  - Transplanted adult bone marrow-derived cells (BMDCs) have been shown to adopt the
      phenotype and function of several nonhematopoietic cell lineages and promote
      tumorigenesis. Beyond its cancer enhancing potential, cell fusion has recently
      emerged as an explanation of how BMDCs regenerate diseased heptocytes, contribute
      to Purkinje neurons and skeletal and cardiac muscle cells, and participate in
      skin and heart regeneration. Although bone marrow-derived epithelial cells also
      have been observed in the intestine, fusion as a mechanism has not been
      investigated. Here, we show that transplanted BMDCs fuse with both normal and
      neoplastic intestinal epithelium. Long-term repopulation by donor-derived cells
      was detected in all principal intestinal epithelial lineages including
      enterocytes, goblet cells, Paneth cells, and enteroendocrine cells, suggesting
      that the fusion partners of the BMDCs are long-lived intestinal progenitors or
      stem cells. Fusion of BMDCs with neoplastic epithelium did not result in tumor
      initiation. Our findings suggest an unexpected role for BMDCs in both
      regeneration and tumorigenesis of the intestine.

PMID- 16606846
TI  - Evidence for C-H cleavage by an iron-superoxide complex in the glycol cleavage
      reaction catalyzed by myo-inositol oxygenase.
AB  - myo-Inositol oxygenase (MIOX) activates O2 at a mixed-valent nonheme
      diiron(II/III) cluster to effect oxidation of its cyclohexan-(1,2,3,4,5,6-hexa)
      ol substrate [myo-inositol (MI)] by four electrons to d-glucuronate. Abstraction
      of hydrogen from C1 by a formally (superoxo)diiron(III/III) intermediate was
      previously proposed. Use of deuterium-labeled substrate, 1,2,3,4,5,6-[2H]6-MI (D6
      MI), has now permitted initial characterization of the C-H-cleaving intermediate.
      The MIOX.1,2,3,4,5,6-[2H]6-MI complex reacts rapidly and reversibly with O2 to
      form an intermediate, G, with a g = (2.05, 1.98, 1.90) EPR signal. The rhombic g
      tensor and observed hyperfine coupling to 57Fe are rationalized in terms of a
      (superoxo)diiron(III/III) structure with coordination of the superoxide to a
      single iron. G decays to H, the intermediate previously detected in the reaction
      with unlabeled substrate. This step is associated with a kinetic isotope effect
      of > or =5, showing that the superoxide-level complex does indeed cleave a C-H(D)
      bond of MI.

PMID- 16606847
TI  - Global traffic and disease vector dispersal.
AB  - The expansion of global air travel and seaborne trade overcomes geographic
      barriers to insect disease vectors, enabling them to move great distances in
      short periods of time. Here we apply a coupled human-environment framework to
      describe the historical spread of Aedes albopictus, a competent mosquito vector
      of 22 arboviruses in the laboratory. We contrast this dispersal with the
      relatively unchanged distribution of Anopheles gambiae and examine possible
      future movements of this malaria vector. We use a comprehensive database of
      international ship and aircraft traffic movements, combined with climatic
      information, to remap the global transportation network in terms of disease
      vector suitability and accessibility. The expansion of the range of Ae.
      albopictus proved to be surprisingly predictable using this combination of
      climate and traffic data. Traffic volumes were more than twice as high on
      shipping routes running from the historical distribution of Ae. albopictus to
      ports where it has established in comparison with routes to climatically similar
      ports where it has yet to invade. In contrast, An. gambiae has rarely spread from
      Africa, which we suggest is partly due to the low volume of sea traffic from the
      continent and, until very recently, a European destination for most flights.

PMID- 16606848
TI  - A Dirichlet process model for detecting positive selection in protein-coding DNA
      sequences.
AB  - Most methods for detecting Darwinian natural selection at the molecular level
      rely on estimating the rates or numbers of nonsynonymous and synonymous changes
      in an alignment of protein-coding DNA sequences. In some of these methods, the
      nonsynonymous rate of substitution is allowed to vary across the sequence,
      permitting the identification of single amino acid positions that are under
      positive natural selection. However, it is unclear which probability distribution
      should be used to describe how the nonsynonymous rate of substitution varies
      across the sequence. One widely used solution is to model variation in the
      nonsynonymous rate across the sequence as a mixture of several discrete or
      continuous probability distributions. Unfortunately, there is little population
      genetics theory to inform us of the appropriate probability distribution for
      among-site variation in the nonsynonymous rate of substitution. Here, we describe
      an approach to modeling variation in the nonsynonymous rate of substitution by
      using a Dirichlet process mixture model. The Dirichlet process allows there to be
      a countably infinite number of nonsynonymous rate classes and is very flexible in
      accommodating different potential distributions for the nonsynonymous rate of
      substitution. We implemented the model in a fully Bayesian approach, with all
      parameters of the model considered as random variables.

PMID- 16606849
TI  - DNA motifs in human and mouse proximal promoters predict tissue-specific
      expression.
AB  - Comprehensive identification of cis-regulatory elements is necessary for
      accurately reconstructing gene regulatory networks. We studied proximal promoters
      of human and mouse genes with differential expression across 56 terminally
      differentiated tissues. Using in silico techniques to discover, evaluate, and
      model interactions among sequence elements, we systematically identified
      regulatory modules that distinguish elevated from inhibited expression in the
      corresponding transcripts. We used these putative regulatory modules to construct
      a single predictive model for each of the 56 tissues. These predictors
      distinguish tissue-specific elevated from inhibited expression with statistical
      significance in 80% of the tissues (45 of 56). The predictors also reveal synergy
      between cis-regulatory modules and explain large-scale tissue-specific
      differential expression. For testis and liver, the predictors include
      computationally predicted motifs. For most other tissues, the predictors reveal
      synergy between experimentally verified motifs and indicate genes that are
      regulated by similar tissue-specific machinery. The identification in proximal
      promoters of cis-regulatory modules with tissue-specific activity lays the
      groundwork for complete characterization and deciphering of cis-regulatory DNA
      code in mammalian genomes.

PMID- 16606851
TI  - Tropical drying trends in global warming models and observations.
AB  - Anthropogenic changes in tropical rainfall are evaluated in a multimodel ensemble
      of global warming simulations. Major discrepancies on the spatial distribution of
      these precipitation changes remain in the latest-generation models analyzed here.
      Despite this uncertainty, we find a number of measures, both global and local, on
      which reasonable agreement is obtained, notably for the regions of drying trend
      (negative precipitation anomalies). Models agree on the overall amplitude of the
      precipitation decreases that occur at the margins of the convective zones, with
      percent error bars of magnitude similar to those for the tropical warming.
      Similar agreement is found on a precipitation climate sensitivity defined here
      and on differential moisture increase inside and outside convection zones, a step
      in a hypothesized causal path leading to precipitation changes. A measure of
      local intermodel agreement on significant trends indicates consistent predictions
      for particular regions. Observed rainfall trends in several data sets show a
      significant summer drying trend in a main region of intermodel agreement: the
      Caribbean/Central-American region.

PMID- 16606850
TI  - Absence of the transcription factor CCAAT enhancer binding protein alpha results
      in loss of myeloid identity in bcr/abl-induced malignancy.
AB  - The lineage-determining transcription factor CCAAT enhancer binding protein alpha
      (C/EBPalpha) is required for myeloid differentiation. Decreased function or
      expression of C/EBPalpha is often found in human acute myeloid leukemia. However,
      the precise impact of C/EBPalpha deficiency on the maturation arrest in
      leukemogenesis is not well understood. To address this question, we used a murine
      transplantation model of a bcr/abl-induced myeloproliferative disease. The
      expression of bcr/abl in C/EBPalphapos fetal liver cells led to a chronic myeloid
      leukemia-like disease. Surprisingly, bcr/abl-expressing C/EBPalpha-/- fetal liver
      cells failed to induce a myeloid disease in transplanted mice, but caused a
      fatal, transplantable erythroleukemia instead. Accordingly, increased expression
      of the transcription factors SCL and GATA-1 in hematopoietic precursor cells of
      C/EBPalpha-/-R01-EY-11298 ) fetal livers was found. The mechanism for the lineage
      shift from myeloid to erythroid leukemia was studied in a bcr/abl-positive cell
      line. Consistent with findings of the transplant model, expression of C/EBPalpha
      and GATA-1 was inversely correlated. Id1, an inhibitor of erythroid
      differentiation, was identified as a critical direct target of C/EBPalpha. Down
      regulation of Id1 by RNA interference impaired C/EBPalpha-induced granulocytic
      differentiation. Taken together, our study provides evidence that myeloid lineage
      identity of malignant hematopoietic progenitor cells requires the residual
      expression of C/EBPalpha.

PMID- 16606852
TI  - Optimal vortex formation as an index of cardiac health.
AB  - Heart disease remains a leading cause of death worldwide. Previous research has
      indicated that the dynamics of the cardiac left ventricle (LV) during diastolic
      filling may play a critical role in dictating overall cardiac health. Hence,
      numerous studies have aimed to predict and evaluate global cardiac health based
      on quantitative parameters describing LV function. However, the inherent
      complexity of LV diastole, in its electrical, muscular, and hemodynamic
      processes, has prevented the development of tools to accurately predict and
      diagnose heart failure at early stages, when corrective measures are most
      effective. In this work, it is demonstrated that major aspects of cardiac
      function are reflected uniquely and sensitively in the optimization of vortex
      formation in the blood flow during early diastole, as measured by a dimensionless
      numerical index. This index of optimal vortex formation correlates well with
      existing measures of cardiac health such as the LV ejection fraction. However,
      unlike existing measures, this previously undescribed index does not require
      patient-specific information to determine numerical index values corresponding to
      normal function. A study of normal and pathological cardiac health in human
      subjects demonstrates the ability of this global index to distinguish disease
      states by a straightforward analysis of noninvasive LV measurements.

PMID- 16606853
TI  - Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase,
      as a Bardet-Biedl syndrome gene (BBS11).
AB  - The identification of mutations in genes that cause human diseases has largely
      been accomplished through the use of positional cloning, which relies on linkage
      mapping. In studies of rare diseases, the resolution of linkage mapping is
      limited by the number of available meioses and informative marker density. One
      recent advance is the development of high-density SNP microarrays for genotyping.
      The SNP arrays overcome low marker informativity by using a large number of
      markers to achieve greater coverage at finer resolution. We used SNP microarray
      genotyping for homozygosity mapping in a small consanguineous Israeli Bedouin
      family with autosomal recessive Bardet-Biedl syndrome (BBS; obesity, pigmentary
      retinopathy, polydactyly, hypogonadism, renal and cardiac abnormalities, and
      cognitive impairment) in which previous linkage studies using short tandem repeat
      polymorphisms failed to identify a disease locus. SNP genotyping revealed a
      homozygous candidate region. Mutation analysis in the region of homozygosity
      identified a conserved homozygous missense mutation in the TRIM32 gene, a gene
      coding for an E3 ubiquitin ligase. Functional analysis of this gene in zebrafish
      and expression correlation analyses among other BBS genes in an expression
      quantitative trait loci data set demonstrate that TRIM32 is a BBS gene. This
      study shows the value of high-density SNP genotyping for homozygosity mapping and
      the use of expression correlation data for evaluation of candidate genes and
      identifies the proteasome degradation pathway as a pathway involved in BBS.

PMID- 16606854
TI  - The molecular basis for differential dioxin sensitivity in birds: role of the
      aryl hydrocarbon receptor.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related halogenated aromatic
      hydrocarbons (HAHs) are highly toxic to most vertebrate animals, but there are
      dramatic differences in sensitivity among species and strains. Aquatic birds
      including the common tern (Sterna hirundo) are highly exposed to HAHs in the
      environment, but are up to 250-fold less sensitive to these compounds than the
      typical avian model, the domestic chicken (Gallus gallus). The mechanism of HAH
      toxicity involves altered gene expression subsequent to activation of the aryl
      hydrocarbon receptor (AHR), a basic helix-loop-helix-PAS transcription factor.
      AHR polymorphisms underlie mouse strain differences in sensitivity to HAHs and
      polynuclear aromatic hydrocarbons, but the role of the AHR in species differences
      in HAH sensitivity is not well understood. Here, we show that although chicken
      and tern AHRs both exhibit specific binding of [3H]TCDD, the tern AHR has a lower
      binding affinity and exhibits a reduced ability to support TCDD-dependent
      transactivation as compared to AHRs from chicken or mouse. We further show
      through use of chimeric AHR proteins and site-directed mutagenesis that the
      difference between the chicken and tern AHRs resides in the ligand-binding domain
      and that two amino acids (Val-325 and Ala-381) are responsible for the reduced
      activity of the tern AHR. Other avian species with reduced sensitivity to HAHs
      also possess these residues. These studies provide a molecular understanding of
      species differences in sensitivity to dioxin-like compounds and suggest an
      approach to using the AHR as a marker of dioxin susceptibility in wildlife.

PMID- 16606855
TI  - Discontinuities in ecological data.

PMID- 16606856
TI  - Genes for susceptibility to violence lurk in the brain.

PMID- 16606857
TI  - Betti numbers of holomorphic symplectic quotients via arithmetic Fourier
      transform.
AB  - A Fourier transform technique is introduced for counting the number of solutions
      of holomorphic moment map equations over a finite field. This technique in turn
      gives information on Betti numbers of holomorphic symplectic quotients. As a
      consequence, simple unified proofs are obtained for formulas of Poincare
      polynomials of toric hyperkahler varieties (recovering results of Bielawski
      Dancer and Hausel-Sturmfels), Poincare polynomials of Hilbert schemes of points
      and twisted Atiyah-Drinfeld-Hitchin-Manin (ADHM) spaces of instantons on C2
      (recovering results of Nakajima-Yoshioka), and Poincare polynomials of all
      Nakajima quiver varieties. As an application, a proof of a conjecture of Kac on
      the number of absolutely indecomposable representations of a quiver is announced.

PMID- 16606858
TI  - Picrotoxin-like channel blockers of GABAA receptors.

PMID- 16606859
TI  - Heart failure: statins for all?

PMID- 16606860
TI  - Is calcium the key for the assessment of progression/regression of coronary
      artery disease?
AB  - Coronary calcium scoring has become a common test for cardiovascular risk
      stratification.

PMID- 16606861
TI  - The role of vasodilators in the prevention and treatment of no-reflow following
      percutaneous coronary intervention.
AB  - The routine use of vasodilators in patients with acute coronary syndromes or
      other groups undergoing percutaneous coronary intervention (PCI) cannot be
      recommended at present. However, in the event of no-reflow occurring following
      PCI, intracoronary adenosine or verapamil should be administered.

PMID- 16606862
TI  - Evaluation of restenosis and extent of coronary artery disease in patients with
      previous percutaneous coronary interventions by dobutamine stress real-time
      myocardial contrast perfusion imaging.
AB  - OBJECTIVES: To assess the accuracy of real-time myocardial contrast perfusion
      imaging (MCPI) for the diagnosis of restenosis and extent of coronary artery
      disease (CAD) in patients with previous percutaneous coronary intervention (PCI).
      METHODS: 56 patients were studied 1.9 (SD 1.4) years after PCI. They underwent
      MCPI with commercially available ultrasound contrast agents (Optison or Definity)
      at rest and at peak dobutamine-atropine stress. Coronary angiography was
      performed within one month. Significant CAD was defined as >or= 50% stenosis in
      >or= 1 major epicardial coronary artery. Significant restenosis was defined as
      >or= 50% stenosis in a coronary segment with previous intervention. RESULTS:
      Reversible perfusion abnormalities were detected in 40 of 43 patients with
      significant CAD and in 4 of 13 patients without (overall sensitivity 93%, 95% CI
      85% to 99%; specificity 69%, 95% CI 44% to 94%; and accuracy 88%, 95% CI 79% to
      96%). Significant restenosis in >or= 1 coronary artery with previous PCI was
      detected in 38 (68%) patients. Reversible perfusion abnormalities were present in
      35 of them (sensitivity 92%, 95% CI 84% to 99%). Reversible perfusion
      abnormalities were detected in >or= 2 vascular distributions in 20 of 28 patients
      with multivessel CAD and in 3 of 28 patients without (sensitivity 71%, 95% CI 55%
      to 88%; specificity 89%, 95% CI 78% to 99%; and accuracy 80%, 95% CI 70% to 91%).
      Restenosis was detected in 41 coronary arteries. Sensitivity of MCPI for regional
      diagnosis of restenosis was 73% (95% CI 60% to 87%), specificity was 75% (95% CI
      60% to 90%), and accuracy was 74% (95% CI 64% to 84%). CONCLUSION: Dobutamine
      stress MCPI is a useful technique for the evaluation of restenosis and extent of
      CAD after PCI.

PMID- 16606863
TI  - Beneficial effects of abciximab in patients with primary percutaneous
      intervention for acute ST segment elevation myocardial infarction in clinical
      practice.
AB  - OBJECTIVES: To assess the safety and effectiveness of abciximab in patients with
      ST elevation myocardial infarction (STEMI) treated with primary percutaneous
      coronary intervention (PCI) in clinical practice. METHODS: Data were analysed of
      2184 consecutive patients treated with primary PCI for acute STEMI and either
      concomitant abciximab or no glycoprotein IIb/IIIa inhibitor (control group), who
      were prospectively enrolled in the Acute Coronary Syndromes (ACOS) registry
      between July 2000 and November 2002. RESULTS: Patients who were treated with
      abciximab were younger than the control group, and fewer of them had a history of
      stroke/transient ischaemic attack and systemic hypertension, but more of them had
      three-vessel coronary artery disease and cardiogenic shock. Cumulated mid-term
      survival for patients treated with abciximab was significantly higher than in the
      control group (91% v 79%, log rank p < 0.05, median observational time 375 days,
      range 12-34 months). The Cox proportional hazards model of mid-term mortality
      after admission with adjustment for baseline characteristics showed that
      mortality was significantly lower in the abciximab group than in the control
      group (hazard ratio 0.68, 95% confidence interval 0.49 to 0.95). Whereas overall
      there was no difference in bleeding complications, patients older than 75 years
      had more major bleeding events with abciximab (12.5% v 3.4%, p = 0.03).
      CONCLUSION: In clinical practice adjunctive treatment with abciximab in patients
      with primary PCI for acute STEMI was associated with a reduction in mid-term
      mortality. The subgroup of patients older than 75 years who were treated with
      abciximab had more major bleeding complications.

PMID- 16606864
TI  - Delayed hyperenhancement in magnetic resonance imaging of left ventricular
      hypertrophy caused by aortic stenosis and hypertrophic cardiomyopathy:
      visualisation of focal fibrosis.
AB  - OBJECTIVE: To compare the extent and distribution of focal fibrosis by gadolinium
      contrast-enhanced magnetic resonance imaging (MRI; delayed hyperenhancement) in
      severe left ventricular (LV) hypertrophy in patients with pressure overload
      caused by aortic stenosis (AS) and with genetically determined hypertrophic
      cardiomyopathy (HCM). METHODS: 44 patients with symptomatic valvular AS (n = 22)
      and HCM (n = 22) were studied. Cine images were acquired with fast imaging with
      steady-state precession (trueFISP) on a 1.5 T scanner (Sonata, Siemens Medical
      Solutions). Gadolinium contrast-enhanced MRI was performed with a segmented
      inversion-recovery sequence. The location, extent and enhancement pattern of
      hyperenhanced myocardium was analysed in a 12-segment model. RESULTS: Mean LV
      mass was 238.6 (SD 75.3) g in AS and 205.4 (SD 80.5) g in HCM (p = 0.17).
      Hyperenhancement was observed in 27% of patients with AS and in 73% of patients
      with HCM (p < 0.01). In AS, hyperenhancement was observed in 60% of patients with
      a maximum diastolic wall thickness >or= 18 mm, whereas no patient with a maximum
      diastolic wall thickness < 18 mm had hyperenhancement (p < 0.05). Patients with
      hyperenhancement had more severe AS than patients without hyperenhancement
      (aortic valve area 0.80 (0.09) cm(2)v 0.99 (0.3) cm(2), p < 0.05; maximum
      gradient 98 (22) mm Hg v 74 (24) mm Hg, p < 0.05). In HCM, hyperenhancement was
      predominant in the anteroseptal regions and patients with hyperenhancement had
      higher end diastolic (125.4 (36.9) ml v 98.8 (16.9) ml, p < 0.05) and end
      systolic volumes (38.9 (18.2) ml v 25.2 (1.7) ml, p < 0.05). The volume of
      hyperenhancement (percentage of total LV myocardium), where present, was lower in
      AS than in HCM (4.3 (1.9)% v 8.6 (7.4)%, p< 0.05). Hyperenhancement was observed
      in 4.5 (3.1) and 4.6 (2.7) segments in AS and HCM, respectively (p = 0.93), and
      the enhancement pattern was mostly patchy with multiple foci. CONCLUSIONS: Focal
      scarring can be observed in severe LV hypertrophy caused by AS and HCM, and
      correlates with the severity of LV remodelling. However, focal scarring is
      significantly less prevalent in adaptive LV hypertrophy caused by AS than in
      genetically determined HCM.

PMID- 16606865
TI  - Relationship between myocardial perfusion and dysfunction in diabetic
      cardiomyopathy: a study of quantitative contrast echocardiography and strain rate
      imaging.
AB  - OBJECTIVE: To use quantitative myocardial contrast echocardiography (MCE) and
      strain rate imaging (SRI) to assess the role of microvascular disease in
      subclinical diabetic cardiomyopathy. METHODS: Stress MCE and SRI were performed
      in 48 patients (22 with type II diabetes mellitus (DM) and 26 controls), all with
      normal left ventricular systolic function and no obstructive coronary disease by
      quantitative coronary angiography. Real-time MCE was acquired in three apical
      views at rest and after combined dipyridamole-exercise stress. Myocardial blood
      flow (MBF) was quantified in the 10 mid- and apical cardiac segments at rest and
      after stress. Resting peak systolic strain rate (SR) and peak systolic strain
      (epsilon) were calculated in the same 10 myocardial segments. RESULTS: The DM and
      control groups were matched for age, sex and other risk factors, including
      hypertension. The DM group had higher body mass index and left ventricular mass
      index. Quantitative SRI analysis was possible in all patients and quantitative
      MCE in 46 (96%). The mean epsilon, SR and MBF reserve were all significantly
      lower in the DM group than in controls, with diabetes the only independent
      predictor of each parameter. No correlation was seen between MBF and SR (r = 
      0.01, p = 0.54) or between MBF and epsilon (r = -0.20, p = 0.20). CONCLUSIONS:
      Quantitative MCE shows that patients with diabetes but no evidence of obstructive
      coronary artery disease have impaired MBF reserve, but abnormal transmural flow
      and subclinical longitudinal myocardial dysfunction are not related.

PMID- 16606866
TI  - APOE alleles are not associated with calcific aortic stenosis.
AB  - OBJECTIVES: To analyse the association of APOE alleles with aortic stenosis (AS)
      in a large study population. METHODS: Patients with AS (n = 538) and a control
      group of the same age without heart disease (n = 536) were recruited. Left heart
      catheterisation was performed and mean gradient, aortic valve area, presence of
      stenotic coronary artery disease (CAD) and cardiovascular risk factors
      (hypercholesterolaemia, hypertension, smoking, diabetes mellitus and family
      history of CAD) were assessed. The frequency of the APOE major alleles e2, e3 and
      e4 was assessed by genotyping the polymorphisms APOE334 and APOE472 with a 5'
      exonuclease assay (TaqMan). RESULTS: Mean gradient across the aortic valve in
      cases was 50 (SD 20) mm Hg corresponding to a mean aortic valve area of 0.84 (SD
      0.34) cm(2). 270 patients with AS had stenotic CAD. Among patients with AS, the
      prevalence of hypercholesterolaemia (64% v 40%, p < 0.001), smoking (43% v 27%, p
      < 0.001), diabetes (27% v 17%, p < 0.01), family history of CAD (30% v 21%, p </=
      0.05), and male sex (65% v 44%, p < 0.001) was higher in those with than in those
      without CAD. The frequency of the major alleles was not different between cases
      and controls (APOE e2: 104 (19.3%) v 94 (17.5%); APOE e3: 319 (59.3%) v 332
      (61.9%); APOE e4: 115 (21.3%) v 110 (20.5%); all p > 0.10). CONCLUSION: APOE e4
      is not associated with AS, reflecting the different genetic backgrounds of CAD
      and AS.

PMID- 16606867
TI  - Effect of aggressive risk factor modification on cardiac events and myocardial
      ischaemia in patients with chronic kidney disease.
AB  - OBJECTIVE: To examine whether aggressive risk factor modification in chronic
      kidney disease (CKD) can limit the development of new ischaemia or reduce cardiac
      events. METHODS: Patients with CKD were randomly assigned to either an aggressive
      risk factor modification strategy (targeted treatment of hypertension,
      dyslipidaemia, homocysteine, haemoglobin and phosphate) or standard care. An
      intention to treat analysis was performed on 152 patients who had baseline
      dobutamine stress echocardiography (DSE), including 107 who had follow-up DSE.
      Biochemical parameters, cardiac risk factors and investigations (ECG, two
      dimensional echocardiography) were recorded at baseline. New ischaemia was
      classed as new or worsening stress wall motion abnormality between follow-up and
      baseline DSE. Patients were followed up for the development of new ischaemia or
      cardiac death, acute coronary syndrome and non-fatal myocardial infarction over
      1.8 years. RESULTS: The development of new ischaemia was common but not different
      between the standard and aggressively treated groups (15 (21%) v 18 (23%), p =
      0.8). Independent predictors of new ischaemia were older age, abnormal ECG,
      higher systolic blood pressure and lower serum high density lipoprotein
      cholesterol, but not treatment arm. The standard and aggressively treated groups
      did not differ in cardiac event rate (10% v 13%, p = 0.6) or all-cause mortality
      (10% v 19%, p = 0.2). In patients with an abnormal baseline DSE (non-diagnostic,
      scar or ischaemia), the event rate was similar (22% v 20%, p = 0.9). CONCLUSION:
      Aggressive risk factor modification in CKD does not limit the development of new
      ischaemia or reduce cardiac events in patients with an abnormal DSE.

PMID- 16606868
TI  - Artificial control of gene expression in mammalian cells by modulating RNA
      interference through aptamer-small molecule interaction.
AB  - Recent studies have uncovered extensive presence and functions of small noncoding
      RNAs in gene regulation in eukaryotes. In particular, RNA interference (RNAi) has
      been the subject of significant investigations for its unique role in post
      transcriptional gene regulation and utility as a tool for artificial gene
      knockdown. Here, we describe a novel strategy for post-transcriptional gene
      regulation in mammalian cells in which RNAi is specifically modulated through RNA
      aptamer-small molecule interaction. Incorporation of an RNA aptamer for
      theophylline in the loop region of a short hairpin RNA (shRNA) designed to
      silence fluorescent reporter genes led to dose-dependent inhibition of RNAi by
      theophylline. shRNA cleavage experiments using recombinant Dicer demonstrated
      that theophylline inhibited cleavage of an aptamer-fused shRNA by Dicer in vitro.
      Inhibition of siRNA production by theophylline was also observed in vivo. The
      results presented here provide the first evidence of specific RNA-small molecule
      interaction affecting RNAi, and a novel strategy to regulate mammalian gene
      expression by small molecules without engineered proteins.

PMID- 16606869
TI  - Idiopathic macular telangiectasia.
AB  - OBJECTIVES: To review the frequency and nature of idiopathic macular
      telangiectasia and to classify the disorders based on new clinical and imaging
      observations. METHODS: A combined retrospective and prospective analysis of newly
      diagnosed patients seen over a period of 3 years. Patients were identified based
      on the Gass-Blodi classification and were studied with biomicroscopy, fluorescein
      angiography, and optical coherence tomography. RESULTS: Ten patients associated
      with aneurysmal telangiectasia (Gass-Blodi group 1) and 26 patients with
      perifoveal telangiectasia (Gass-Blodi group 2) were recruited. None with
      occlusive telangiectasia (Gass-Blodi group 3) were identified. New observations
      based on clinical, fluorescein angiographic, and optical coherence tomographic
      findings were made. CONCLUSIONS: Our series was similar to that in the Gass-Blodi
      study in terms of frequency. New observations in groups 1 and 2 have expanded our
      knowledge of the clinical spectrum of these disorders. A simplified
      classification termed idiopathic macular telangiectasia with 2 distinct types
      (type I, or aneurysmal telangiectasia, and type II, or perifoveal telangiectasia)
      was proposed to produce a better understanding of the entities and to enhance
      teaching and research. The third type, occlusive telangiectasia, has been omitted
      from our classification based on its rarity and presence of capillary
      nonperfusion rather than macular telangiectasia as the primary abnormality.

PMID- 16606870
TI  - Altered expression of neurotransmitter receptors and neuromediators in vernal
      keratoconjunctivitis.
AB  - BACKGROUND: There is growing evidence that autonomic innervation is involved in
      the pathogenesis of mucus hypersecretion, goblet cell hyperplasia, and
      conjunctival hyperreactivity. OBJECTIVE: To determine the expression of
      neurotransmitters and neurotransmitter receptors in vernal keratoconjunctivitis
      (VKC) tissues to evaluate whether neurogenic inflammation plays a role in this
      ocular atopic-related disorder. METHODS: Biopsy specimens of upper tarsal
      conjunctiva from 8 VKC patients with active inflammation and from 4 healthy
      subjects were processed for immunohistochemistry using anti-M1, anti-M2, and anti
      M3 muscarinic receptors; beta1-adrenergic receptor; vasoactive intestinal
      peptide; nerve growth factor; and protein gene product 9.5, a marker of nerve
      fibers. RESULTS: In the conjunctival epithelium of VKC patients, M1 muscarinic
      receptor, nerve growth factor, and protein gene product 9.5 expression were
      decreased, whereas M2 and M3 muscarinic receptors and beta1-adrenergic receptor
      were irregularly distributed, compared with control subjects. Neurotransmitter
      receptors and vasoactive intestinal peptide expression were increased in the
      substantia propria-localized infiltrate of VKC compared with healthy tissue.
      Nerve growth factor and protein gene product 9.5 staining was also enhanced in
      the conjunctival stroma of VKC vs healthy conjunctiva. CONCLUSIONS: The inflamed
      conjunctiva of VKC patients demonstrated an obvious alteration in muscarinic and
      beta1-adrenergic receptor, vasoactive intestinal peptide, protein gene product
      9.5, and nerve growth factor expression. These results substantiate the
      involvement of an autonomic dysfunction in the pathogenesis of VKC.

PMID- 16606871
TI  - Effect of central corneal thickness, corneal curvature, and axial length on
      applanation tonometry.
AB  - OBJECTIVE: To evaluate the effect of central corneal thickness (CCT), corneal
      curvature, and axial length on applanation tonometry in an in vivo study.
      METHODS: In a masked, prospective clinical trial, we examined 125 eyes of 125
      patients scheduled for cataract surgery. Corneal curvature was measured by means
      of keratometry and axial length by A-scan ultrasonography. By cannulating the
      anterior chamber before surgery, intraocular pressure (IOP) was set to 20, 35,
      and 50 mm Hg in a closed system by means of a water column. After measuring
      thickness, the IOP was measured with an applanation tonometer. Pearson product
      moment correlations and multiple linear regression analyses were performed, and
      significance levels were evaluated by the paired, 2-tailed t test. RESULTS: The
      difference between measured and real IOP was significantly dependent (P < .001)
      on CCT. The associations between IOP and corneal curvature or IOP and axial
      length were not statistically significant (P = .31). The association between IOP
      reading and CCT is shown in the "Dresdner correction table," which illustrates an
      approximately 1-mm Hg correction for every 25-microm deviation from a CCT of 550
      microm. The correction values were positive as thickness decreased and negative
      as thickness increased. CONCLUSIONS: Central corneal thickness significantly
      affects IOP readings obtained by applanation tonometry according to the Goldmann
      principle. A correction of IOP readings by considering CCT according to the
      Dresdner correction table might be helpful for determining an accurate IOP value.

PMID- 16606872
TI  - In vitro fluoroquinolone resistance in staphylococcal endophthalmitis isolates.
AB  - OBJECTIVE: To evaluate the in vitro susceptibility and cross-resistance of
      gatifloxacin and moxifloxacin vs older fluoroquinolones among coagulase-negative
      staphylococci recovered from patients with clinical endophthalmitis. METHODS: A
      combination of E tests and disk diffusion methods was used to determine in vitro
      susceptibility and cross-resistance for 111 coagulase-negative staphylococci
      isolates recovered during a 15-year period (January 1, 1990, to December 31,
      2004) against 5 fluoroquinolones. RESULTS: In vitro susceptibilities (percentage
      sensitive) in descending order were as follows: gatifloxacin, 74.5%;
      moxifloxacin, 72.1%; levofloxacin, 69.3%; ciprofloxacin, 65.6%, and ofloxacin,
      60.4%. More than 65% of the coagulase-negative staphylococci resistant to
      ciprofloxacin (n = 38) demonstrated in vitro cross-resistance to gatifloxacin (25
      [65.8%] of 38) and moxifloxacin (27 [71.1%] of 38). During the initial 5 years
      (January 1, 1990, to December 31, 1994), 96.6% of the coagulase-negative
      staphylococci were sensitive to gatifloxacin and moxifloxacin, with minimal
      inhibitory concentration required to inhibit or kill 90% of the isolates of 0.19
      microg/mL and 0.12 microg/mL, respectively. During the last 5-year period
      (January 1, 2000, to December 31, 2004), the percentage of sensitive coagulase
      negative staphylococci declined to 65.4% for gatifloxacin and moxifloxacin
      (P=.02). Minimal inhibitory concentration required to inhibit or kill 90% of the
      isolates was 32 microg/mL or greater for both drugs. CONCLUSIONS: Gatifloxacin
      and moxifloxacin demonstrated an in vitro efficacy of less than 80% for coagulase
      negative staphylococci endophthalmitis in the present study. Ciprofloxacin
      resistance may serve as a surrogate for concurrent in vitro resistance for
      gatifloxacin and moxifloxacin. Resistance increased significantly during the last
      5 years. Declining in vitro susceptibility to gatifloxacin and moxifloxacin may
      have important implications for the prevention and treatment of postoperative
      endophthalmitis.

PMID- 16606873
TI  - Sequenced combined intravitreal triamcinolone and indocyanine green angiography
      guided photodynamic therapy for retinal angiomatous proliferation.
AB  - OBJECTIVE: To study sequenced combined therapy using intravitreal triamcinolone
      acetonide followed by photodynamic therapy for the treatment of retinal
      angiomatous proliferation. METHODS: Patients newly diagnosed as having retinal
      angiomatous proliferation underwent intravitreal triamcinolone injection to
      reduce intraretinal and subretinal exudation, followed 7 to 14 days later by
      indocyanine green angiography-guided photodynamic therapy with verteporfin.
      Complete ocular examination, fluorescein angiography, indocyanine green
      angiography, and optical coherence tomography were performed at baseline and at
      standard intervals thereafter. RESULTS: Twenty-seven eyes of 26 patients
      underwent this sequenced combined treatment and were followed up for 12 months.
      The triamcinolone injection reduced the cystoid edema before photodynamic
      therapy. Complete resolution of the angiographic leakage was achieved in 89% of
      eyes. Visual acuity improved in 37% and was stable in 52% of eyes. Eight eyes
      developed recurrent leakage after 3 to 11 months. Complete resolution of leakage
      was observed after subsequent treatment. CONCLUSIONS: This sequenced combined
      treatment in patients with retinal angiomatous proliferation was effective in
      reducing or eliminating the edema, achieving rapid regression of
      neovascularization, and stabilizing or improving visual acuity. To our knowledge,
      no study to date has achieved such promising results in the management of retinal
      angiomatous proliferation. A randomized clinical trial is under way to compare
      sequential and simultaneous combined therapy.

PMID- 16606874
TI  - Multiple evanescent white dot syndrome.
AB  - OBJECTIVES: To study the clinical and angiographic features of lesions in a case
      series of multiple evanescent white dot syndrome (MEWDS), to describe a newly
      recognized clinical variation of the disorder, and to gain insight into its
      pathophysiological nature. METHODS: Five patients with MEWDS (selected based on
      angiographic manifestations of the disorder) were examined using slitlamp
      biomicroscopy and studied using fluorescein angiography and indocyanine green
      angiography. RESULTS: All 5 patients exhibited the newly recognized angiographic
      features termed dots and spots, which varied in size and location in the fundus.
      Small dots were in the inner retina or at the level of the retinal pigment
      epithelium, and larger spots were more external in the subpigment epithelial
      area. All patients exhibited other characteristics typical of MEWDS, including
      field loss and foveal granularity. CONCLUSIONS: In this case series of MEWDS, a
      clinical variant consisting of dual-layered lesions with specific features on
      clinical examination, fluorescein angiography, and indocyanine green angiography
      was identified. On late indocyanine green angiography, these lesions produced
      highly specific findings of small hypofluorescent lesions overlying larger
      hypofluorescent lesions. Based on the angiographic findings, it seems as if MEWDS
      is a chorioretinopathy with varying degrees of retinal and choroidal involvement.

PMID- 16606875
TI  - Extended follow-up of small melanocytic choroidal tumors treated with
      transpupillary thermotherapy.
AB  - OBJECTIVE: To report our longer-term follow-up observations in patients with
      small choroidal melanomas primarily treated with transpupillary thermotherapy
      (TTT). METHODS: In this noncomparative interventional case series, 40 patients
      with small melanocytic tumors of the choroid (thickness <3.5 mm) underwent TTT.
      Follow-up examinations including ophthalmoscopy, ultrasonography, and fundus
      photography were conducted at 24 to 48 hours, 2 to 6 weeks, and 6-month intervals
      after treatment. RESULTS: Forty patients (mean age, 58 years) with small
      melanocytic tumors underwent TTT. Mean follow-up in all patients was 42 months.
      In most cases TTT resulted in tumor regression. Thirty-one (77.5%) of 40 tumors
      did not recur after initial treatment with TTT. In 5 (12.5%) of 40 tumors with
      initial basal diameters ranging from 4 x 2.75 mm to 7.5 x 6 mm and a mean initial
      thickness of 2.0 mm, edge recurrences developed, which were satisfactorily
      treated with additional TTT (4 cases) or cryotherapy (1 case). The mean interval
      between initial TTT and recurrence in this subgroup was 15 months (range, 7-22
      months). Of 36 eyes that were successfully treated with TTT or cryotherapy, 26
      eyes (72%) had posttreatment visual acuity better than or equal to pretreatment
      visual acuity. Four (10%) of 40 tumors were not controlled with TTT and
      eventually required brachytherapy (n = 1), proton radiation (n = 1), or
      enucleation (n = 2). The initial basal diameters of these tumors ranged from 7.5
      x 7.5 mm to 9 x 7.5 mm, with a mean initial thickness of 2.6 mm. The mean
      interval between treatment and determination of treatment failure was 22 months
      (range, 7-30 months). CONCLUSIONS: Transpupillary thermotherapy resulted in tumor
      regression of most small melanocytic choroidal tumors. Tumor edge recurrences
      were successfully treated with additional TTT in most cases. Four tumors required
      irradiation or enucleation because of treatment failures with TTT. Transpupillary
      thermotherapy as a stand-alone therapy is insufficient for some small choroidal
      melanomas.

PMID- 16606876
TI  - The Pediatric Vision Screener III: detection of strabismus in children.
AB  - OBJECTIVE: To evaluate the clinical performance of the Pediatric Vision Screener
      (PVS) in children in a pediatric ophthalmology office setting. METHODS: Seventy
      seven subjects between 2 and 18 years of age received gold-standard orthoptic
      examinations and were classified as at risk for amblyopia if strabismus or
      anisometropia (>1.50 diopters) was present. Strabismus was subclassified as
      variable or constant. The subjects were then tested with the PVS, which produced
      a pass or refer recommendation based on a binocularity score. The PVS also
      produced a yield score to indicate the subject's interest in the target.
      Sensitivity and specificity for amblyopia risk detection were calculated.
      RESULTS: Binocularity as determined by the PVS was greater than 65% for all
      controls and less than 20% for all subjects with constant strabismus.
      Binocularity ranged from 0% to 52% in subjects with variable strabismus. All
      subjects with anisometropia and no strabismus had binocularity scores less than
      10%. CONCLUSIONS: The PVS identified strabismus, when present, in all subjects
      and identified 3 subjects with anisometropia as well. The PVS shows potential to
      address a lack of screening instrumentation appropriate for use with preschool
      aged children.

PMID- 16606877
TI  - Staining ability and biocompatibility of brilliant blue G: preclinical study of
      brilliant blue G as an adjunct for capsular staining.
AB  - OBJECTIVE: To evaluate the effectiveness and biocompatibility of brilliant blue G
      (BBG) for capsular visualization for continuous curvilinear capsulorrhexis.
      METHODS: The capsular staining ability of BBG was evaluated at graded
      concentrations of 10.0, 1.0, 0.5, 0.25, 0.1, and 0.01 mg/mL in enucleated pig's
      eyes. The biocompatibility of BBG was assessed in rat's eyes for 2 months. The
      eyes were analyzed using light, fluorescence, transmission electron, and scanning
      electron microscopy. TUNEL (terminal deoxynucleotidyl transferase-mediated biotin
      deoxyuridine triphosphate nick-end labeling) was used to detect apoptotic cells,
      and endothelial cell counts were analyzed using scanning electron microscopy. The
      results were compared using indocyanine green and trypan blue. RESULTS: The BBG
      improved capsular visualization, and a complete capsulorrhexis could be
      performed. In the rat model, no apparent toxic effect was observed using
      biomicroscopy during 2 months. Histologically, BBG showed satisfactory
      biocompatibility. Apoptotic cell death of the endothelial cells was detected in
      only the trypan blue group. In contrast to BBG, indocyanine green and trypan blue
      showed degeneration of corneal endothelial cells using transmission and scanning
      electron microscopy. CONCLUSION: The BBG contributed to better capsular
      visualization and caused no apparent complications to the corneal
      endothelium.Clinical Relevance The BBG is effective and safe capsular staining
      for continuous curvilinear capsulorrhexis.

PMID- 16606878
TI  - Minocycline delays death of retinal ganglion cells in experimental glaucoma and
      after optic nerve transection.
AB  - OBJECTIVE: To evaluate the effect of minocycline hydrochloride on the survival of
      retinal ganglion cells (RGCs) in glaucomatous rat eyes and rat eyes after optic
      nerve transection (ONT). METHODS: The effect of intraperitoneal injections of
      minocycline at dosages of 15 mg/kg per day, 22 mg/kg per day, and 45 mg/kg per
      day was evaluated and compared with saline in ONT (n = 174) and experimental
      glaucoma (n = 51). RESULTS: The mean +/- SEM survival rate of RGCs 1 week after
      ONT was significantly higher with minocycline at dosages of 15 mg/kg per day (36%
      +/- 3%; n = 9; P = .04), 22 mg/kg per day (44% +/- 2%; n = 15; P = .001), and 45
      mg/kg per day (39% +/- 3%; n = 10; P = .008) compared with saline (29% +/- 2%; n
      = 28). Minocycline at a dosage of 22 mg/kg per day was also significantly
      neuroprotective compared with saline 2 weeks after ONT (mean +/- SEM survival
      rate, 5% +/- 1% vs 3% +/- 0.4%, respectively; n = 20 [10 rats in each group]; P =
      .03). In experimental glaucoma, the mean +/- SEM percentage of RGCs after 4 weeks
      was 84% +/- 4% in the minocycline group (n = 15) compared with 65% +/- 4% in the
      saline group (n = 18) (P = .003). Apoptosis of RGCs was significantly delayed by
      minocycline 4 days and 1 week after ONT. CONCLUSION: Minocycline significantly
      enhances the survival of RGCs after ONT and in experimental glaucoma by delaying
      the apoptosis pathway. CLINICAL RELEVANCE: The safety record of minocycline and
      its ability to penetrate the blood-brain barrier suggest that this drug is a
      promising neuroprotective drug for optic nerve injuries.

PMID- 16606879
TI  - Prevalence of age-related maculopathy in older Europeans: the European Eye Study
      (EUREYE).
AB  - OBJECTIVE: To estimate the prevalence of age-related maculopathy in an older
      population from 7 European countries. METHODS: Randomly sampled people 65 years
      and older were invited to an eye examination in centers across 7 European
      countries (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain).
      Fundus images of each eye were graded at a single reading center. Prevalence
      rates were calculated for stage of age-related maculopathy with 95% confidence
      intervals (CIs) estimated for clustered data. RESULTS: Of 5040 participants (45%
      response rate), 4753 (2128 men and 2625 women) had gradable fundus images. The
      prevalences were grade 0, 47.59% (95% CI, 43.53%-51.65%); grade 1, 36.48% (95%
      CI, 32.66%-40.30%); grade 2, 10.14% (95% CI, 8.92% to 11.37%); grade 3, 2.46%
      (95% CI, 1.79%-3.13%); and grade 4 (age-related macular degeneration [AMD]),
      3.32% (95% CI, 2.52%-4.13%) and large drusen only (> or = 125 microm), 15.41%
      (95% CI, 13.61%-17.21%). The prevalence of geographic atrophic AMD was 1.2% (95%
      CI, 0.8%-1.7%) and of neovascular AMD, 2.3% (95% CI, 1.7%-2.9%). The prevalence
      of bilateral AMD was 1.4% (95% CI, 1.0%-1.8%). CONCLUSION: Age-specific
      prevalences of age-related maculopathy in the European Eye Study (EUREYE) are
      similar to other population-based studies in Western populations.

PMID- 16606881
TI  - Laser suture lysis through thick blebs using the Blumenthal lens.

PMID- 16606880
TI  - Cognitive impairment in the Age-Related Eye Disease Study: AREDS report no. 16.
AB  - OBJECTIVE: To investigate potential associations between cognitive function
      and/or impairment and age-related macular degeneration (AMD) and visual
      impairment in the Age-Related Eye Disease Study (AREDS). METHODS: The AREDS is an
      11-center natural history study of AMD and age-related cataract. The AREDS
      Cognitive Function Battery was administered to 2946 participants. The battery
      consists of 6 neuropsychological tests measuring performance in several cognitive
      domains. The Dunnett multiple comparison test was used to identify differences by
      AMD and visual acuity severity. The relationship with cognitive impairment was
      also assessed using logistic regression. RESULTS: Mean scores of instruments in
      the AREDS Cognitive Function Battery declined with increased macular
      abnormalities and reduced visual acuity. After adjustment for age, sex, race,
      education, smoking status, diabetes mellitus, hypertension, and depression,
      increased macular abnormalities (trend P value <.05) reduced mean cognitive
      function scores as measured by the Modified Mini-Mental State Examination and the
      Wechsler Logical Memory Scale. Reduced vision was found to be associated with
      reduced mean cognitive function scores as measured by the Modified Mini-Mental
      State Examination and letter and verbal fluency tasks. Persons with vision worse
      than 20/40 OU were more likely to be cognitively impaired (Modified Mini-Mental
      State Examination score <80) (odds ratio, 2.88 [95% confidence interval, 1.75
      4.76]) compared with persons with visual acuity of 20/40 or better OU.
      CONCLUSION: These data suggest a possible association of advanced AMD and visual
      acuity with cognitive impairment in older persons.

PMID- 16606882
TI  - Temporary eyelid closure applique.
AB  - Tarsorrhaphy is used for the treatment of severe ocular surface disorders and for
      damage from ocular exposure. The temporary tarsorrhaphy has been shown to aid in
      the healing of corneal epithelial defects. A variety of temporary techniques have
      been suggested that allow eyelid closure not only to enable epithelial healing
      but also to allow access to the eye. We describe a temporary eyelid closure
      applique, similar to the Stamler eyelid splint, that provides nearly complete
      closure of the eyelid that will last for days. The technique is inexpensive, can
      be applied by a family member with minimal training, and can be used in almost
      any setting.

PMID- 16606883
TI  - Modification of a soft contact lens for use during irrigation and aspiration in
      the penetrating keratoplasty triple procedure.
AB  - The purpose of the present study was to design and test a new soft contact lens
      with 2 holes for improvement of both visibility and the rate of lens cortex
      aspiration during cataract surgery using the penetrating keratoplasty triple
      procedure. Two groups of 9 age-matched patients underwent the penetrating
      keratoplasty triple procedure with or without the newly designed contact lens.
      The use of the new soft contact lens reduced the time required for irrigation and
      aspiration of the lens cortex from 183.8 +/- 92.2 to 121.2 +/- 27.9 seconds
      (P<.05); the total operative and open-sky times also significantly decreased. In
      addition, use of the lens greatly improved visibility of the surgical field
      during cataract extraction. The newly designed soft contact lens thus improves
      management of the lens cortex during the penetrating keratoplasty triple
      procedure.

PMID- 16606884
TI  - Ophthalmologic findings in Cornelia de Lange syndrome: a genotype-phenotype
      correlation study.
AB  - OBJECTIVE: To evaluate individuals with Cornelia de Lange syndrome previously
      screened for mutations in the NIPBL gene for genotype-phenotype correlations with
      regard to severity of ophthalmologic findings. METHODS: Fifty-four patients with
      Cornelia de Lange syndrome (26 mutation positive and 28 mutation negative) with
      varying extent and severity of ophthalmologic findings participated in the study.
      We conducted a retrospective analysis of ophthalmologic data obtained through
      survey responses and medical records. The severity of nasolacrimal duct
      obstruction, myopia, ptosis, and strabismus was classified. The severity of eye
      findings was compared relative to the presence vs the absence of mutations in the
      coding region of NIPBL and relative to mutations predicted to result in a
      truncated protein (nonsense and frameshift mutations) vs missense mutations.
      Fisher exact test was used to determine the significance of these correlations.
      RESULTS: A trend toward increased ptosis severity was found among individuals
      with truncating (nonsense and frameshift) mutations compared with individuals
      with missense mutations (P = .07). CONCLUSION: NIPBL may be directly involved in
      ptosis pathogenesis. CLINICAL RELEVANCE: Elucidating the pathogenetic mechanisms
      of ophthalmologic morbidities in patients with de Lange syndrome may lead to more
      effective treatment.

PMID- 16606885
TI  - Perspectives on verteporfin therapy combined with intravitreal corticosteroids.

PMID- 16606886
TI  - Should corticosteroids be considered as part of the standard care with
      photodynamic therapy?

PMID- 16606887
TI  - Macular telangiectasia: a simplified classification.

PMID- 16606888
TI  - Complement factor H and macular degeneration: the genome yields an important
      clue.

PMID- 16606889
TI  - Green cataract.
AB  - The green cataract seen in the 16th to 18th centuries was reinterpreted in the
      19th century (on the basis of pathological examinations) to be a greenish color
      of the light returning through the pupil in an eye with absolute glaucoma and not
      due to a greenish discoloration of a cataract. Were the older observers in error?
      It seems unlikely. This article presents photographs of true green cataracts--ie,
      opaque lenses of greenish color--from my own practice; a published photograph of
      a green cataract; and histopathological documentation of the cause, iron (blood
      pigment).

PMID- 16606890
TI  - Epibulbar seeding at the site of a transvitreal fine-needle aspiration biopsy.

PMID- 16606891
TI  - Two cases of Reis-Bucklers corneal dystrophy (granular corneal dystrophy type
      III) caused by spontaneous mutations in the TGFBI gene.

PMID- 16606892
TI  - Corneal graft folds: a complication of deep lamellar endothelial keratoplasty.

PMID- 16606893
TI  - Pineal cyst simulating pinealoblastoma in 11 children with retinoblastoma.

PMID- 16606894
TI  - Photodynamic therapy for exudative hamartoma in tuberous sclerosis.

PMID- 16606895
TI  - Systemic sarcoidosis manifested as unilateral eyelid retraction.

PMID- 16606896
TI  - Anti-inflammatory fibrosis suppression in threatened trabeculectomy bleb failure.

PMID- 16606897
TI  - We can aim at better results in coming years.

PMID- 16606898
TI  - The ophthalmologist or the optometrist as surgeon.

PMID- 16606899
TI  - Complications of anterior chamber fixation of posterior chamber intraocular
      lenses.

PMID- 16606900
TI  - Observed growth in small melanocytic choroidal tumors.

PMID- 16606901
TI  - Ocular brucellosis vs Vogt-Koyanagi-Harada syndrome.

PMID- 16606902
TI  - Experimental implantation and long-term testing of an intraocular vision aid in
      rabbits.

PMID- 16606903
TI  - Mature teratoma of the lateral ventricle in adulthood: preoperative CT and MRI
      diagnosis.

PMID- 16606904
TI  - Human African trypanosomiasis: in and out of Africa.

PMID- 16606905
TI  - Risks, benefits, and consent in the age of gene therapy.

PMID- 16606906
TI  - Practice Parameters for Parkinson disease: signposts for clinical research.

PMID- 16606907
TI  - Practice Parameter: diagnosis and prognosis of new onset Parkinson disease (an
      evidence-based review): report of the Quality Standards Subcommittee of the
      American Academy of Neurology.
AB  - OBJECTIVE: To define key issues in the diagnosis of Parkinson disease (PD), to
      define features influencing progression, and to make evidence-based
      recommendations. Two clinical questions were identified: 1) Which clinical
      features and diagnostic modalities distinguish PD from other parkinsonian
      syndromes? 2) Which clinical features predict rate of disease progression?
      METHODS: Systematic review of the literature was completed. Articles were
      classified according to a four-tiered level of evidence scheme. Recommendations
      were based on the evidence. RESULTS AND CONCLUSIONS: 1. Early falls, poor
      response to levodopa, symmetry of motor manifestations, lack of tremor, and early
      autonomic dysfunction are probably useful in distinguishing other parkinsonian
      syndromes from Parkinson disease (PD). 2. Levodopa or apomorphine challenge and
      olfactory testing are probably useful in distinguishing PD from other
      parkinsonian syndromes. 3. Predictive factors for more rapid motor progression,
      nursing home placement, and shorter survival time include older age at onset of
      PD, associated comorbidities, presentation with rigidity and bradykinesia, and
      decreased dopamine responsiveness. Future research into methods for earlier and
      more accurate diagnosis of the disease and identification and clarification of
      predictive factors of rapid disease progression is warranted.

PMID- 16606908
TI  - Practice Parameter: neuroprotective strategies and alternative therapies for
      Parkinson disease (an evidence-based review): report of the Quality Standards
      Subcommittee of the American Academy of Neurology.
AB  - OBJECTIVE: To define key issues in the management of Parkinson disease (PD)
      relating to neuroprotective strategies and alternative treatments, and to make
      evidence-based treatment recommendations. METHODS: Two clinical questions were
      identified. 1) In a patient diagnosed with PD, are there any therapies that can
      slow disease progression? 2) Are there any nonstandard pharmacologic or
      nonpharmacologic therapies that have been shown to improve motor function in PD?
      Articles were classified according to a four-tiered level of evidence scheme.
      Recommendations were based on the evidence. RESULTS AND CONCLUSIONS: 1. Levodopa
      does not appear to accelerate disease progression. 2. No treatment has been shown
      to be neuroprotective. 3. There is no evidence that vitamin or food additives can
      improve motor function in PD. 4. Exercise may be helpful in improving motor
      function. 5. Speech therapy may be helpful in improving speech volume. 6. No
      manual therapy has been shown to be helpful in the treatment of motor symptoms,
      although studies in this area are limited. Further studies using a rigorous
      scientific method are needed to determine efficacy of alternative therapies.

PMID- 16606909
TI  - Practice Parameter: treatment of Parkinson disease with motor fluctuations and
      dyskinesia (an evidence-based review): report of the Quality Standards
      Subcommittee of the American Academy of Neurology.
AB  - OBJECTIVE: To make evidence-based treatment recommendations for the medical and
      surgical treatment of patients with Parkinson disease (PD) with levodopa-induced
      motor fluctuations and dyskinesia. To that end, five questions were addressed. 1.
      Which medications reduce off time? 2. What is the relative efficacy of
      medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does
      deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus
      interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off
      time, dyskinesia, and antiparkinsonian medication usage and improve motor
      function? 5. Which factors predict improvement after DBS? METHODS: A 10-member
      committee including movement disorder specialists and general neurologists
      evaluated the available evidence based on a structured literature review
      including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004.
      RESULTS, CONCLUSIONS, AND RECOMMENDATIONS: 1. Entacapone and rasagiline should be
      offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and
      tolcapone should be considered to reduce off time (Level B). Apomorphine,
      cabergoline, and selegiline may be considered to reduce off time (Level C). 2.
      The available evidence does not establish superiority of one medicine over
      another in reducing off time (Level B). Sustained release carbidopa/levodopa and
      bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may
      be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the
      STN may be considered to improve motor function and reduce off time, dyskinesia,
      and medication usage (Level C). There is insufficient evidence to support or
      refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing
      off time, dyskinesia, or medication usage, or to improve motor function. 5.
      Preoperative response to levodopa predicts better outcome after DBS of the STN
      (Level B).

PMID- 16606910
TI  - Practice Parameter: evaluation and treatment of depression, psychosis, and
      dementia in Parkinson disease (an evidence-based review): report of the Quality
      Standards Subcommittee of the American Academy of Neurology.
AB  - OBJECTIVE: To make evidence-based treatment recommendations for patients with
      Parkinson disease (PD) with dementia, depression, and psychosis based on these
      questions: 1) What tools are effective to screen for depression, psychosis, and
      dementia in PD? 2) What are effective treatments for depression and psychosis in
      PD? 3) What are effective treatments for PD dementia or dementia with Lewy bodies
      (DLB)? METHODS: A nine-member multispecialty committee evaluated available
      evidence from a structured literature review using MEDLINE, and the Cochrane
      Database of Health and Psychosocial Instruments from 1966 to 2004. Additional
      articles were identified by panel members. RESULTS: The Beck Depression Inventory
      I, Hamilton Depression Rating Scale, and Montgomery Asberg Depression Rating
      Scale should be considered to screen for depression in PD (Level B). The Mini
      Mental State Examination and the Cambridge Cognitive Examination should be
      considered to screen for dementia in PD (Level B). Amitriptyline may be
      considered to treat depression in PD without dementia (Level C). For psychosis in
      PD, clozapine should be considered (Level B), quetiapine may be considered (Level
      C), but olanzapine should not be considered (Level B). Donepezil or rivastigmine
      should be considered for dementia in PD (Level B) and rivastigmine should be
      considered for DLB (Level B). CONCLUSIONS: Screening tools are available for
      depression and dementia in patients with PD, but more specific validated tools
      are needed. There are no widely used, validated tools for psychosis screening in
      Parkinson disease (PD). Clozapine successfully treats psychosis in PD.
      Cholinesterase inhibitors are effective treatments for dementia in PD, but
      improvement is modest and motor side effects may occur.

PMID- 16606911
TI  - Does the arousal system contribute to near death experience?
AB  - The neurophysiologic basis of near death experience (NDE) is unknown. Clinical
      observations suggest that REM state intrusion contributes to NDE. Support for the
      hypothesis follows five lines of evidence: REM intrusion during wakefulness is a
      frequent normal occurrence, REM intrusion underlies other clinical conditions,
      NDE elements can be explained by REM intrusion, cardiorespiratory afferents evoke
      REM intrusion, and persons with an NDE may have an arousal system predisposing to
      REM intrusion. To investigate a predisposition to REM intrusion, the life-time
      prevalence of REM intrusion was studied in 55 NDE subjects and compared with that
      in age/gender-matched control subjects. Sleep paralysis as well as sleep-related
      visual and auditory hallucinations were substantially more common in subjects
      with an NDE. These findings anticipate that under circumstances of peril, an NDE
      is more likely in those with previous REM intrusion. REM intrusion could promote
      subjective aspects of NDE and often associated syncope. Suppression of an
      activated locus ceruleus could be central to an arousal system predisposed to REM
      intrusion and NDE.

PMID- 16606912
TI  - The association of CAG repeat length with clinical progression in Huntington
      disease.
AB  - OBJECTIVE: To determine whether the rate of clinical progression in Huntington
      disease (HD) is influenced by the size of the CAG expansion. METHODS: The dataset
      consisted of 3,402 examinations of 512 subjects seen through the Baltimore
      Huntington's Disease Center. Subjects were seen for a mean of 6.64 visits, with
      mean follow-up of 6.74 years. Subjects were administered the Quantified
      Neurological Examination, with its subsets the Motor Impairment and Chorea
      Scores, the Mini-Mental State Examination, and the HD Activities of Daily Living
      (ADL) Scale. RESULTS: In an analysis based on the Random Effects Model, CAG
      length was significantly associated with the rate of progression of all measures
      except chorea and ADL. There was a significant interaction term between CAG
      length and disease duration for all measures except chorea. Further graphical
      exploration of the data supported these linear models and suggested that subjects
      at the low end of the expanded CAG repeat range may experience a more benign late
      course. CONCLUSIONS: CAG repeat length has a small effect on rate of progression
      that may be clinically important over time. Individuals with the shortest
      expansions appear to have the best prognosis. These effects of the CAG length may
      be relevant in the analysis of clinical trials.

PMID- 16606913
TI  - Clinical features associated with costs in early AD: baseline data from the
      Predictors Study.
AB  - BACKGROUND: Few studies on cost of caring for patients with Alzheimer disease
      (AD) have simultaneously considered multiple dimensions of disease costs and
      detailed clinical characteristics. OBJECTIVE: To estimate empirically the
      incremental effects of patients' clinical characteristics on disease costs.
      METHODS: Data are derived from the baseline visit of 180 patients in the
      Predictors Study, a large, multicenter cohort of patients with probable AD
      followed from early stages of the disease. All patients initially lived at home,
      in retirement homes, or in assisted living facilities. Costs of direct medical
      care included hospitalizations, outpatient treatment and procedures, assistive
      devices, and medications. Costs of direct nonmedical care included home health
      aides, respite care, and adult day care. Indirect costs were measured by
      caregiving time. Patients' clinical characteristics included cognitive status,
      functional capacity, psychotic symptoms, behavioral problems, depressive
      symptoms, extrapyramidal signs, comorbidities, and duration of illness. RESULTS:
      A 1-point increase in the Blessed Dementia Rating Scale score was associated with
      a $1,411 increase in direct medical costs and a $2,718 increase in unpaid
      caregiving costs. Direct medical costs also were $3,777 higher among subjects
      with depressive symptoms than among those who were not depressed. CONCLUSIONS:
      Medical care costs and unpaid caregiving costs relate differently to patients'
      clinical characteristics. Poorer functional status is associated with higher
      medical care costs and unpaid caregiving costs. Interventions may be particularly
      useful if targeted in the areas of basic and instrumental activities of daily
      living.

PMID- 16606914
TI  - Altered brain white matter integrity in healthy carriers of the APOE epsilon4
      allele: a risk for AD?
AB  - BACKGROUND: Previous research has shown that polymorphisms of apolipoprotein E
      (APOE) represent genetic risk factors for dementia and for cognitive impairment
      in the elderly. The neural mechanisms by which these genetic variations influence
      behavioral performance or clinical severity are not well understood. METHODS: The
      authors used diffusion tensor imaging to investigate ultrastructural properties
      in brain white matter to detect pathologic processes that modify tissue
      integrity. Sixty participants were included in the study of which 30 were
      homozygous for the APOE epsilon3 allele, 10 were homozygous for the APOE epsilon4
      allele, and 20 had the APOE epsilon34 allele combination. All individuals were
      non-demented, and the groups were matched on demographic variables and cognitive
      performance. RESULTS: The results showed a decline in fractional anisotropy, a
      marker for white matter integrity, in the posterior corpus callosum of epsilon4
      carriers compared to non-carriers. Additional sites of altered white matter
      integrity included the medial temporal lobe. CONCLUSIONS: Although the mechanism
      underlying vulnerability of white matter tracts in APOE epsilon4 carriers is
      still unknown, these findings suggest that increased genetic risk for developing
      Alzheimer disease is associated with changes in microscopic white matter
      integrity well before the onset of dementia.

PMID- 16606915
TI  - Syncope in migraine: the population-based CAMERA study.
AB  - OBJECTIVE: To examine the association between migraine and syncope-related
      autonomic nervous system (ANS) symptoms. METHODS: A population-based study among
      migraineurs with and without aura (n = 323) and control subjects (n = 153) was
      conducted. A systematic questionnaire and cardiovascular measurements during
      rest, while standing, and after venipuncture addressed the prevalence of syncope,
      orthostatic intolerance, orthostatic hypotension (OH), and the postural
      tachycardia syndrome (POTS) in migraineurs and control subjects. RESULTS: The
      lifetime prevalence of syncope in all participants was 41%, more often in women
      (45 vs 32%; p = 0.02). Compared with control subjects, migraineurs had a higher
      lifetime prevalence of syncope (46 vs 31%; p = 0.001), frequent syncope (five or
      more attacks) (13 vs 5%; p = 0.02), and orthostatic intolerance (32 vs 12%; p <
      0.001). There was no association between ANS symptoms and the severity of
      migraine or migraine subtype. Cardiovascular measurements and the prevalence of
      POTS and OH did not differ significantly between migraineurs and control
      subjects. CONCLUSION: This population-based study demonstrated an elevated
      prevalence of syncope and orthostatic intolerance in migraineurs without clear
      interictal signs of autonomic nervous system dysfunction.

PMID- 16606916
TI  - Postoperative seizures after extratemporal resections and hemispherectomy in
      pediatric epilepsy.
AB  - OBJECTIVES: To estimate frequency and risk factors for acute postoperative
      seizures (APOS) within the first week after extratemporal cortical resection
      (ETR) and hemispherectomy (HS) in children and to assess the predictive value of
      APOS on long-term seizure outcome in this group. METHODS: The authors conducted a
      retrospective analysis of children (< 18 years), who underwent ETR or HS for
      intractable epilepsy between 1995 and 2002. APOS features and seizure outcome
      after ETR or HS were obtained at 6, 12, and 24 months. Univariate logistic
      regression was used for risk factors of APOS and life table analysis and log rank
      tests for seizure outcome at 0 to 6, 6 to 12, and 12 to 24 months. RESULTS: Of
      132 patients, 34 (26%) had APOS. APOS were more frequent after ETR (26/71) than
      HS (8/61) (p < 0.01). APOS, irrespective of their timing, number, semiology, or
      other perioperative complications, were an independent predictor of poor
      postoperative seizure outcome at 2 years (p < 0.001). The estimated odds of
      postoperative Engel class I outcome in the APOS vs non-APOS categories was 0.27
      (73% less likely) for 0- to 6-month, 0.22 (78% less likely) for 6- to 12-month,
      and 0.13 (87% less likely) for the 12- to 24-month intervals. CONCLUSIONS: Acute
      postoperative seizures (APOS) occur in 26% children, and the risk is higher after
      extratemporal cortical resection than hemispherectomy. APOS predict a poor
      postoperative seizure outcome at 6, 12, and 24 months. This study is useful for
      counseling families after epilepsy surgery. It also suggests that APOS may not be
      discounted as "benign" in research studies that evaluate seizure outcomes after
      epilepsy surgery.

PMID- 16606917
TI  - Novel truncating and missense mutations of the KCC3 gene associated with
      Andermann syndrome.
AB  - BACKGROUND: Andermann syndrome (OMIM 218000) is an autosomal recessive motor
      sensory neuropathy associated with developmental and neurodegenerative defects.
      The cerebral MRI reveals a variable degree of agenesis of the corpus callosum.
      Recently, truncating mutations of the KCC3 gene (also known as SLC12A6) have been
      associated with Andermann syndrome. METHODS: The authors assessed clinically and
      genetically three isolated cases from Germany and Turkey with symptoms consistent
      with Andermann syndrome. RESULTS: The authors detected four novel mutations
      within the KCC3 gene in their patients: two different truncating mutations in the
      first patient, a homozygous truncating mutation in the second, and a homozygous
      missense mutation in the third patient. In contrast to the classic phenotype of
      the Andermann syndrome linked to truncating KCC3 mutations the phenotype and the
      course of the disease linked to the missense mutation appeared to be different
      (i.e., showing additional features like diffuse and widespread white matter
      abnormalities). CONCLUSIONS: Not only truncating but also missense mutations of
      the KCC3 gene are associated with Andermann syndrome. Different types of KCC3
      mutations may determine different clinical phenotypes.

PMID- 16606918
TI  - Widespread and intense BOLD changes during brief focal electrographic seizures.
AB  - BACKGROUND: Combined recording of EEG and fMRI has shown changes in blood
      oxygenation level dependent (BOLD) signal during focal interictal epileptic
      spikes. Due to difficult assessment of seizures inside the scanner little is
      known about BOLD changes during seizures. OBJECTIVES: To describe BOLD changes
      related to brief focal electrographic seizures in a patient with right temporo
      parietal gray matter nodular heterotopia. METHODS: The patient underwent two EEG
      fMRI sessions during which several focal seizures were recorded. EEG was acquired
      continuously during scanning and seizure timing was used for statistical
      analysis. Functional maps were thresholded to disclose positive (activation) and
      negative (deactivation) BOLD changes. RESULTS: Twenty-five focal electrographic
      seizures were analyzed, consisting of runs of polyspikes lasting 2 to 6 s in the
      right temporal region. Activation included a large volume, involving the
      heterotopia and the abnormal temporo-parietal cortex overlying the nodule, with a
      clear maximum over the angular gyrus. Deactivation was bilateral and maximum in
      the occipital regions. The hemodynamic response function showed a return to
      baseline of the BOLD signal 30 s after seizure end. CONCLUSIONS: The brief focal
      seizures resulted in high amplitude and widespread blood oxygenation level
      dependent (BOLD) responses taking 30 s to return to baseline. This suggests that
      such brief events could have important behavioral consequences despite absent
      overt manifestations. A clear focal BOLD peak was found at some distance from the
      main EEG discharge, raising the possibility that the seizure could have started
      in a region that did not generate a visible EEG change despite its superficial
      location.

PMID- 16606919
TI  - Multiple sclerosis frequency in Israel's diverse populations.
AB  - BACKGROUND: Israel has served for almost half a century as a site for
      epidemiologic studies of multiple sclerosis (MS). Its small geographic size, well
      equipped, accessible, and subsidized health facilities, trained physicians,
      detailed census data, and a National MS Register, maintained since 1960, offer
      advantages for accurate determinations of MS frequency in its diverse
      populations. METHOD: The authors calculated age-specific prevalence of MS in
      Israeli-born Jewish inhabitants, immigrant Jews from Europe/America and from
      North Africa/Asia, Israeli-born Christian and Moslem Arabs, Druze, and Bedouins.
      RESULTS: Prevalence rate of MS per 10(5) population on June 30, 2000, for each of
      these groups in the order listed was 61.6, 53.7, and 27.9 for the Jewish groups
      and 35.3, 14.7, 10.9, and 17.3 for the non-Jewish groups. Three tiers in MS
      prevalence were apparent. The highest rates were in Israeli-born Jews and in
      Jewish immigrants from Europe/America (significantly higher in the former than
      the latter). Jewish immigrants from African/Asian countries and Christian Arabs
      had intermediate MS rates (significantly lower than in the first two groups but
      not significantly different from each other). Moslem Arabs, Druze, and Bedouins
      had the lowest rates of MS (significantly lower than in the intermediate group
      but not significantly different from each other). CONCLUSION: Diverse ethnic
      groups living in the same geographic area may have significantly different
      frequencies of MS.

PMID- 16606920
TI  - Global and regional volume changes in the brains of patients with
      phenylketonuria.
AB  - BACKGROUND: Although phenylketonuria is a treatable disease, patients with late
      or nonoptimal phenylalanine-restricted diet may experience brain damage. The
      authors used tridimensional MRI and a voxelwise analysis method to investigate
      possible volume changes in the brain parenchyma of patients with phenylketonuria.
      METHODS: The authors assessed 27 treated patients (mean age +/- SD, 20 +/- 7
      years) and 27 matched control subjects. Global tissue volumes were compared, and
      statistical parametric maps of between-group regional volume differences were
      obtained for gray and white matter. Anatomic data were correlated with relevant
      clinical and biochemical variables. RESULTS: Patients with phenylketonuria showed
      smaller gray matter volumes that were associated with lower IQ and older age at
      diagnosis. Voxel-based maps revealed that significant gray matter volume
      reduction occurred in motor and premotor cortex and thalamus. A relative increase
      in gray matter volume was observed in the ventral part of the striatum. The
      authors found no group differences for global white matter measurements. Higher
      recent phenylalanine levels, however, were associated with larger global white
      matter volume in early-treated patients. Voxel-based maps showed a relative
      volume reduction in periventricular white matter and a relative increase in the
      region of the internal capsule, extending to the adjacent thalamus and striatum.
      CONCLUSIONS: Treated patients may show significant gray and white matter volume
      changes related to the duration and strict observation of dietary treatment.
      Further studies are needed to investigate whether the presence of neurologic
      symptoms may be explained by specific anatomic alterations.

PMID- 16606921
TI  - Click-evoked vestibulo-ocular reflex: stimulus-response properties in superior
      canal dehiscence.
AB  - BACKGROUND: An enlarged, low-threshold click-evoked vestibulo-ocular reflex (VOR)
      can be averaged from the vertical electro-oculogram in a superior canal
      dehiscence (SCD), a temporal bone defect between the superior semicircular canal
      and middle cranial fossa. OBJECTIVE: To determine the origin and quantitative
      stimulus-response properties of the click-evoked VOR. METHODS: Three-dimensional,
      binocular eye movements evoked by air-conducted 100-microsecond clicks (110 dB
      normal hearing level, 145 dB sound pressure level, 2 Hz) were measured with dual
      search coils in 11 healthy subjects and 19 patients with SCD confirmed by CT
      imaging. Thresholds were established by decrementing loudness from 110 dB to 70
      dB in 10-dB steps. Eye rotation axis of click-evoked VOR computed by vector
      analysis was referenced to known semicircular canal planes. Response
      characteristics were investigated with regard to enhancement using trains of
      three to seven clicks with 1-millisecond interclick intervals, visual fixation,
      head orientation, click polarity, and stimulation frequency (2 to 15 Hz).
      RESULTS: In subjects and SCD patients, click-evoked VOR comprised upward,
      contraversive-torsional eye rotations with onset latency of approximately 9
      milliseconds. Its eye rotation axis aligned with the superior canal axis,
      suggesting activation of superior canal receptors. In subjects, the amplitude was
      less than 0.01 degrees, and the magnitude was less than 3 degrees/second; in SCD,
      the amplitude was up to 60 times larger at 0.66 degrees, and its magnitude was
      between 5 and 92 degrees/second, with a threshold 10 to 40 dB below normal (110
      dB). The click-evoked VOR magnitude was enhanced approximately 2.5 times with
      trains of five clicks but was unaffected by head orientation, visual fixation,
      click polarity, and stimulation frequency up to 10 Hz; it was also present on the
      surface electro-oculogram. CONCLUSION: In superior canal dehiscence, clicks
      evoked a high-magnitude, low-threshold, 9-millisecond-latency vestibulo-ocular
      reflex that aligns with the superior canal, suggesting superior canal receptor
      hypersensitivity to sound.

PMID- 16606922
TI  - Motor system inhibition in dopa-responsive dystonia and its modulation by
      treatment.
AB  - Dopa-responsive dystonia (DRD) causes dystonia-parkinsonism, which is abolished
      by levodopa. The authors assessed short intracortical inhibition and
      facilitation, silent period, blink reflex recovery cycle, and reciprocal
      inhibition in seven patients with DRD on and off treatment. Short intracortical
      inhibition and blink reflex recovery cycle were reduced, but increased with
      treatment. Silent period was normal on and off treatment. Third phase of
      reciprocal inhibition was reduced on and off treatment. A discrete pattern of
      motor inhibitory dysfunction occurs in DRD.

PMID- 16606923
TI  - Changes in forearm reciprocal inhibition following pallidal stimulation for
      dystonia.
AB  - The authors recorded forearm H reflex reciprocal inhibition and clinical outcome
      in eight patients with primary torsion dystonia before and 1, 3, and 6 months
      after pallidal deep brain stimulation (DBS). There was progressive increase in
      reciprocal inhibition after surgery, which correlated with clinical improvement.
      The authors conclude that pallidal DBS for dystonia results in functional
      reorganization of the nervous system, which includes a long-term increase in
      spinal inhibition.

PMID- 16606924
TI  - Lethal African trypanosomiasis in a traveler: MRI and neuropathology.
AB  - The authors report a case of human African trypanosomiasis with CNS involvement
      caused by Trypanosoma brucei rhodesiense in a 52-year-old woman, which relapsed
      after melarsoprol treatment. After a second regimen, she developed a severe toxic
      polyneuropathy, progressing to coma and eventually death. MRI revealed rapidly
      progressive multiple white matter lesions as well as damage of the central gray
      matter and cortex. The autopsy results confirmed the diagnosis of human African
      trypanosomiasis.

PMID- 16606925
TI  - Nonsteroidal anti-inflammatory drugs and the incidence of Parkinson disease.
AB  - Animal and epidemiologic studies suggest that nonsteroidal anti-inflammatory
      drugs (NSAIDs) decrease the incidence of Parkinson disease (PD). The authors
      studied 1,258 PD cases and 6,638 controls from the General Practice Research
      Database. The odds ratios (95% CI) for ever vs never use were 0.93 (0.80 to 1.08)
      for nonaspirin NSAIDs, 1.29 (1.05 to 1.58) for aspirin, and 1.16 (1.00 to 1.35)
      for acetaminophen. Nonaspirin NSAID use was associated with a higher risk in
      women and a lower risk in men.

PMID- 16606926
TI  - Epilepsia partialis continua of the abdominal muscles with transient MRI
      abnormalities.

PMID- 16606927
TI  - Alpha-synuclein pathology in the spinal cords of neurologically asymptomatic aged
      individuals.
AB  - The authors assessed the frequency of spinal cord alpha-synuclein pathology in
      neurologically asymptomatic individuals older than 60 years of age (N = 106).
      Using alpha-synuclein immunohistochemistry, nine cases (8%) had incidental Lewy
      neurites in the intermediolateral column and at least some alpha-synuclein
      pathology in the dorsal motor nucleus of the vagus, locus ceruleus, and central
      raphe nucleus. Sparse alpha-synuclein pathology was also detected in the
      substantia nigra, basal forebrain, amygdala, or cortex in all but two cases.

PMID- 16606928
TI  - Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic
      exon.
AB  - The authors describe a Japanese autosomal recessive spastic ataxia of Charlevoix
      Saguenay (ARSACS) patient with a compound heterozygous mutation (32627
      32636delACACTGTTAC and 31760delT) in a new exon of the SACS gene. The new exons
      upstream of the gigantic one should be analyzed when a case is clinically
      compatible with ARSACS, even without any mutation in the gigantic exon.

PMID- 16606929
TI  - Prolonged but reversible migraine-like episodes long after cranial irradiation.
AB  - The authors describe three patients with prolonged but reversible episodes of
      severe headaches and focal neurologic deficits developing years after irradiation
      for cranial neoplasms. Despite extensive evaluations, etiology of episodes in
      these three and eight other previously reported patients remains undetermined.
      Whether they all have the same condition is uncertain. Although some had cortical
      gadolinium enhancement on MRI, all 11 patients returned to baseline over hours to
      weeks.

PMID- 16606930
TI  - Opioidergic changes in the pineal gland and hypothalamus in cluster headache: a
      ligand PET study.
AB  - Using PET with the opioidergic ligand [11C]diprenorphine, the authors demonstrate
      decreased tracer binding in the pineal gland of cluster headache patients vs
      healthy volunteers. Opioid receptor availability in the hypothalamus and
      cingulate cortex depended on the duration of the headache disorder. Therefore,
      the pathophysiology of cluster headache may relate to opioidergic dysfunction in
      circuitries generating the biologic clock.

PMID- 16606931
TI  - Infectious mononucleosis and unilateral tongue writhing.

PMID- 16606932
TI  - In vivo cholinergic circuit evaluation in frontotemporal and Alzheimer dementias.
AB  - The test of short latency afferent inhibition (SAI) of the motor cortex is
      helpful in demonstrating dysfunction of central cholinergic circuits in Alzheimer
      disease (AD). The authors evaluated SAI in 20 patients with frontotemporal
      dementia (FTD) and compared data with those from 20 patients with AD and 20
      controls. SAI was normal in FTD, whereas it was reduced in AD. SAI may represent
      an additional tool to discriminate FTD from AD.

PMID- 16606933
TI  - Lariat branch point mutation in the dysferlin gene with mild limb-girdle muscular
      dystrophy.
AB  - The authors report a genotype-phenotype correlation in a limb-girdle muscular
      dystrophy 2B family. Two severely affected sisters were homozygous for a
      dysferlin null mutation. Their mildly affected compound heterozygous mother
      harbored, in addition to one null allele, an in-frame exon-skipping allele caused
      by a novel lariat branch point mutation. The dysferlin molecule arising from the
      latter allele appeared to partially complement the null mutation, likely
      accounting for the mother's mild phenotype.

PMID- 16606934
TI  - Randomized controlled phase II trial of glatiramer acetate in ALS.
AB  - The authors conducted a randomized controlled trial to test the safety and
      immunology of glatiramer acetate in ALS. Twenty treated patients were randomly
      assigned to daily or biweekly injections. Ten control patients were selected from
      another trial and followed up concurrently. Injection reactions were the only
      common adverse event (p = 0.01). Treated patients showed enhanced lymphocyte
      proliferation (p = 0.02). The safety profile and immune effects support
      conducting larger trials of dose selection and efficacy.

PMID- 16606935
TI  - Cerebral vasculopathy with aneurysm formation in HIV-infected young adults.

PMID- 16606936
TI  - Neurolisteriosis presenting as cervical myelitis in an immunocompetent patient.

PMID- 16606937
TI  - Delayed amnesic syndrome after riluzole autointoxication in Huntington disease.

PMID- 16606938
TI  - Hanging leg syndrome: combined bilateral femoral and sciatic neuropathies.

PMID- 16606939
TI  - Bilateral cerebellar infarction caused by dominant medial posterior inferior
      cerebellar artery.

PMID- 16606940
TI  - The dedicated doctor.

PMID- 16606941
TI  - Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes,
      and phenotypes.

PMID- 16606942
TI  - The impact of standardized stroke orders on adherence to best practices.

PMID- 16606943
TI  - Quantitative proton MRS of Pelizaeus-Merzbacher disease: evidence of dys- and
      hypomyelination.

PMID- 16606944
TI  - Effect of genetic modifiers on cerebral lesions in Fabry disease.

PMID- 16606945
TI  - Women in neurology.

PMID- 16606946
TI  - MRI-guided, open trial of abciximab for ischemic stroke within a 3- to 24-hour
      window.

PMID- 16606947
TI  - Quebec's proposed wait time guarantees.

PMID- 16606948
TI  - Alberta's hybrid public- private "third way".

PMID- 16606949
TI  - Quebec included in CaRMS match.

PMID- 16606950
TI  - BC to reform health care.

PMID- 16606951
TI  - Manitoba pharmacists' association clarifies Plan B regulations.

PMID- 16606952
TI  - Happy doctors? Satisfaction with professional life.

PMID- 16606954
TI  - Prioritizing and stopping prescription medicines.

PMID- 16606955
TI  - An unusual case of endocarditis.

PMID- 16606956
TI  - Does pioglitazone prevent macrovascular events in patients with type 2 diabetes?

PMID- 16606957
TI  - A case of recurrent meningitis.

PMID- 16606958
TI  - Chagas disease: hidden affliction and visible neglect.

PMID- 16606959
TI  - The costs of planned cesarean versus planned vaginal birth in the Term Breech
      Trial.
AB  - BACKGROUND: The Term Breech Trial compared the safety of planned cesarean and
      planned vaginal birth for breech presentations at term. The combined outcome of
      perinatal or neonatal death and serious neonatal morbidity was found to be
      significantly lower among babies delivered by planned cesarean section. In this
      study we conducted a cost analysis of the 2 approaches to breech presentations at
      delivery. METHODS: We used a third-party-payer (i.e., Ministry of Health)
      perspective. We included all costs for physician services and all hospital
      related costs incurred by both the mother and the infant. We collected health
      care utilization and outcomes for all study participants during the trial. We
      used only the utilization data from countries with low national rates of
      perinatal death (< or = 20/1000). Seven hospitals across Canada (4 teaching and 3
      community centres) were selected for unit cost calculations. RESULTS: The
      estimated mean cost of a planned cesarean was significantly lower than that of a
      planned vaginal birth (7165 dollars v. 8042 dollars per mother and infant; mean
      difference -877 dollars, 95% credible interval -1286 dollars to -473 dollars).
      The estimated mean cost of a planned cesarean was lower than that of a planned
      vaginal birth for both women having a first birth (7255 dollars v. 8440 dollars)
      and women having had at least one prior birth (7071 dollars v. 7559 dollars).
      Although the treatment effect was largest in the subgroup of women having their
      first child, there was no statistically significant interaction between treatment
      and parity since the 95% credible intervals for difference in treatment effects
      between parity equalling zero and parity of one or greater all include zero.
      INTERPRETATION: Planned cesarean section was found to be less costly than planned
      vaginal birth for the singleton fetus in a breech presentation at term in the
      Term Breech Trial.

PMID- 16606960
TI  - The economic case for planned cesarean section for breech presentation at term.

PMID- 16606961
TI  - Do manufacturers of brand-name drugs engage in price competition? An analysis of
      introductory prices.

PMID- 16606963
TI  - One size fits all?

PMID- 16606962
TI  - Heterozygous familial hypercholesterolemia: an underrecognized cause of early
      cardiovascular disease.
AB  - Heterozygous familial hypercholesterolemia (HeFH) is a monogenic disorder that
      affects about 1 in 500 people, with a higher prevalence in certain subpopulations
      such as people of Quebecois, Christian Lebanese and Dutch South Afrikaner
      extraction. HeFH is characterized by cholesterol deposits affecting the corneas,
      eyelids and extensor tendons; elevated plasma concentrations of low-density
      lipoprotein (LDL) cholesterol; and accelerated vascular disease, especially
      coronary artery disease (CAD). Although HeFH is genetically heterogeneous, it is
      most often caused by heterozygous mutations in the LDLR gene encoding the LDL
      receptor. We describe a man who was diagnosed with HeFH after he had a myocardial
      infarction at 33 years of age. By DNA sequence analysis, he was found to have a
      heterozygous splicing mutation in his LDLR gene. This discovery expanded the
      growing mutational spectrum in patients with HeFH in Ontario. Given that HeFH is
      a treatable cause of early vascular disease, it is important that this condition
      be recognized, diagnosed and treated in affected patients; but as yet, there is
      no consensus on the best approach. Diagnostic criteria based on family history
      and clinical presentation have been proposed for patients with suspected HeFH.
      Biochemical or molecular screening might be considered to detect new cases of
      HeFH in populations with a relatively high HeFH prevalence and a relatively small
      number of possible causative mutations. So far, however, the most cost-effective
      and efficient systematic strategy to detect previously undiagnosed cases of HeFH
      is still cascade testing: clinical and biochemical screening of close relatives
      of the proband patient diagnosed with HeFH. Pharmacologic treatment of HeFH is
      cost-effective.

PMID- 16606964
TI  - Science and journalism: never the two shall meet?

PMID- 16606965
TI  - Science and journalism: never the two shall meet?

PMID- 16606968
TI  - Ginseng enhances the effectiveness of DHEA.

PMID- 16606969
TI  - Sentinel lymph node histopathology in breast cancer: minimal disease versus
      artifact.

PMID- 16606970
TI  - Axillary sentinel lymph nodes can be falsely positive due to iatrogenic
      displacement and transport of benign epithelial cells in patients with breast
      carcinoma.
AB  - PURPOSE: Immunohistochemical (IHC) staining for cytokeratins (CK) is common
      practice in evaluating sentinel lymph nodes (SLNs) in patients with breast
      carcinoma. IHC positivity typically indicates metastasis. SLN procedures are
      increasingly common in patients with pure intraductal carcinoma (DCIS).
      Iatrogenic epithelial cell displacement and benign transport of breast epithelial
      cells into axillary lymph nodes are recently described phenomena. We report 25
      cases in which these factors probably resulted in benign epithelial cells in
      axillary SLNs (ie, false positivity). METHODS: We reviewed 25 cases of CK
      positive SLNs in which the epithelial cells had histologic and IHC
      characteristics different from their respective patients' underlying breast
      carcinomas. RESULTS: In all cases, the cytologic features of the epithelial cells
      in the SLNs were benign, and 22 matched those of corresponding intraductal
      papillomas that were involved by or were separate from the DCIS in the original
      cores or surgical biopsies. Fifteen cases were pure DCIS; most invasive tumors
      were smaller than 1.0 cm. In six carcinomas (DCIS) showing strong Her-2/neu
      staining, the corresponding epithelial cells in the SLNs were negative. In 13
      tumors that were strongly and uniformly positive for estrogen receptor (ER), the
      cytokeratin-positive cells in the SLNs were negative for ER. Nineteen cases
      showed benign epithelial cell displacement at the biopsy site. CONCLUSION:
      Epithelial cells in SLNs may result from transport of displaced cells, usually
      originating in intraductal papillomas. Positive immunohistochemical results in
      SLNs should be interpreted with extreme caution to avoid automatically concluding
      that such cells represent metastasis. Sentinel lymph nodes in breast carcinoma
      can be falsely positive.

PMID- 16606971
TI  - Bortezomib therapy in patients with relapsed or refractory lymphoma: potential
      correlation of in vitro sensitivity and tumor necrosis factor alpha response with
      clinical activity.
AB  - PURPOSE: To determine the efficacy of bortezomib in patients with lymphoid
      malignancy, correlating clinical response with effect on plasma cytokines and in
      vitro activity in primary cultures. PATIENTS AND METHODS: Patients received
      bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11 of a 3-week cycle. Plasma tumor
      necrosis factor alpha (TNF-alpha) and interleukin-6 were measured before each
      treatment, and bortezomib activity was examined in patient samples grown in
      primary culture. RESULTS: Fifty-one patients received a total of 193 cycles of
      treatment. Twenty-four patients had mantle cell lymphoma (MCL), 13 had follicular
      lymphoma (FL), six had lymphoplasmacytic lymphoma, six had Hodgkin's disease
      (HD), and one each had diffuse large B-cell lymphoma and adult T-cell
      leukemia/lymphoma. Patients were heavily pretreated with a median of four
      previous therapies. Significant grade 3 to 4 toxicities were thrombocytopenia (n
      = 22), fatigue (n = 10), and peripheral neuropathy (n = 3). Seven patients with
      MCL responded to treatment (one complete response, six partial responses [PRs];
      overall response rate, 29%). Two patients with FL achieved a late PR 3 months
      after discontinuing therapy. Two patients with Waldenstrom's macroglobulinemia
      and one patient with HD achieved a PR. MCL primary cultures demonstrated greater
      sensitivity to bortezomib than FL (median 50% effective concentration for
      viability, 209 nmol/L v 1,311 nmol/L, respectively; P = .07), which correlated
      with clinical response. A median reduction in plasma TNF-alpha of 98% was
      observed in six patients with MCL who responded to bortezomib compared with a
      reduction of 38% in six nonresponders (P = .07). CONCLUSION: Bortezomib
      demonstrates encouraging efficacy in MCL in heavily pretreated individuals.
      Response was associated with a reduction in plasma TNF-alpha and in vitro
      sensitivity in a small number of patients.

PMID- 16606972
TI  - Sequential preoperative or postoperative docetaxel added to preoperative
      doxorubicin plus cyclophosphamide for operable breast cancer:National Surgical
      Adjuvant Breast and Bowel Project Protocol B-27.
AB  - PURPOSE: This study was designed to determine the effect of adding docetaxel (T)
      to preoperative doxorubicin and cyclophosphamide (AC) on breast cancer response
      rates and disease-free survival (DFS) and overall survival (OS). PATIENTS AND
      METHODS: Women with operable breast cancer (N = 2,411) were randomly assigned to
      receive preoperative AC followed by surgery, AC followed by T and surgery, or AC
      followed by surgery and then T. Tamoxifen was initiated concurrently with
      chemotherapy. Median time on study for 2,404 patients with follow-up was 77.9
      months. RESULTS: Addition of T to AC did not significantly impact DFS or OS.
      There were trends toward improved DFS with addition of T. The addition of T
      reduced the incidence of local recurrences as first events (P = .0034).
      Preoperative T, but not postoperative T, significantly improved DFS in patients
      who had a clinical partial response after AC (hazard ratio [HR] = 0.71; 95% CI,
      0.55 to 0.91; P = .007). Pathologic complete response, which was doubled by
      addition of preoperative T, was a significant predictor of OS regardless of
      treatment (HR = 0.33; 95% CI, 0.23 to 0.47; P < .0001). Pathologic nodal status
      after chemotherapy was a significant predictor of OS (P < .0001). CONCLUSION: The
      addition of preoperative or postoperative T after preoperative AC did not
      significantly affect OS, slightly improved DFS, and decreased the incidence of
      local recurrences. The sample size of this study was not sufficient to yield
      significance for the moderate DFS improvement. Concurrent use of tamoxifen may
      have limited the impact of adding T.

PMID- 16606973
TI  - Habitat targeting for controlling aquatic stages of malaria vectors in Africa.

PMID- 16606976
TI  - The synergism of N,N-diethyl-m-toluamide (DEET) effects by a carbamate is a novel
      and new observation.

PMID- 16606977
TI  - Experimentally infected human body lice (pediculus humanus humanus) as vectors of
      Rickettsia rickettsii and Rickettsia conorii in a rabbit model.
AB  - The human body louse, the natural vector of Rickettsia prowazekii, is able to
      experimentally transmit the normally flea-borne rickettsia R. typhi, suggesting
      that the relationships between the body louse and rickettsiae are not specific.
      We used our experimental infection model to test the ability of body lice to
      transmit two prevalent tick-borne rickettsiae. Each of two rabbits was made
      bacteremic by injecting intravenously 2 x 10(6) plaque-forming units of either R.
      rickettsii or R. conorii. Four hundred body lice were infected by feeding on the
      bacteremic rabbit and were compared with 400 uninfected lice. Each louse group
      was fed once a day on a separate seronegative rabbit. The survival of infected
      lice was not different from that of uninfected controls. Lice remained infected
      for their lifespan, excreted R. rickettsii and R. conorii in their feces, but did
      not transmit the infection to their progeny. The nurse rabbit of uninfected lice
      remained asymptomatic and seronegative. Those rabbits used to feed infected lice
      developed bacteremia and seroconverted. Although the body louse is not a known
      vector of spotted fevers, it was able in our study to acquire, maintain, and
      transmit both R. rickettsii and R. conorii.

PMID- 16606978
TI  - Experimental infection of human body lice with Acinetobacter baumannii.
AB  - The human body louse is currently recognized as a vector of Rickettsia
      prowazekii, Borrelia recurrentis, and Bartonella quintana. Previous studies have
      reported the isolation of Acinetobacter baumannii from the body lice of homeless
      patients. To study how the body louse acquires A. baumannii, we infected a rabbit
      by infusing 2 x 10(6) colony-forming units of the louse strain of A. baumannii.
      Two hundred body lice were infected by feeding on the bacteremic rabbit and
      compared with 200 uninfected lice and two groups of 200 lice feeding on rabbits
      infected either with another strain of A. baumannii or A. lwoffii. Each louse
      group received maintenance feedings once a day on another seronegative rabbit.
      Body lice that fed on rabbits infused with each Acinetobacter species
      demonstrated a generalized infection. The body lice did not transmit their
      infection to the nurse rabbit by bite while feeding or to their progeny (eggs and
      larvae). The lice excreted living Acinetobacter species within their feces. Only
      the louse strain of A. baumannii was pathogenic for the body louse. An increased
      mortality rate was observed between the second and third days post-infection;
      however, they remained infected for their lifespan.

PMID- 16606979
TI  - First molecular detection of Rickettsia felis in fleas from Algeria.
AB  - Fleas collected in Algeria in the district of Oran between July and September
      2003 were tested by polymerase chain reaction for the presence of Rickettsia spp.
      DNA using primers amplifying gltA and OmpA genes. Two gltA sequences identical to
      those of an emerging pathogen, Rickettsia felis, were detected including i) R.
      felis California 2 in Ctenocephalides canis from rodents and ii) R. felis RF2125
      in Archeopsylla erinacei from hedgehogs.

PMID- 16606980
TI  - Prevalence of and factors associated with Helicobacter pylori infection in
      children in the north of Vietnam.
AB  - The study aimed at evaluating the seroprevalence of and sociodemographic, health,
      lifestyle, and environmental hygiene conditions associated with Helicobacter
      pylori infection in Vietnamese children. Data from 824 children, aged from 6
      months to 15 years and gastrointestinal symptom free when consulted, admitted to
      a university hospital, were collected using a structured questionnaire and ELISA
      test for H. pylori infection. The data were examined using univariate and
      multivariate analyses. H. pylori seroprevalence was 34.0%. Age groups from 3 to 6
      years and older than 6, and number of offspring were positively and independently
      associated with H. pylori seropositivity [adjusted OR (95% CI): 2.9 (1.5-5.5);
      1.9 (1.1-3.1) and 1.8 (1.1-2.6), respectively]. Breastfeeding more than 6 months
      was negatively and independently associated with H. pylori seropositivity
      [adjusted OR (95% CI): 0.5 (0.3-0.9)]. Mother's age, history of allergy, gastro
      duodenal disease history in the past, initiating collective life before 6 years,
      sharing bed with parents and time of bed sharing with parents > 24 months were
      positively but not independently associated with H. pylori seropositivity. None
      of the other environmental or lifestyle conditions examined was associated with
      H. pylori infection. Our results support person-to-person transmission and the
      role of sociodemographic factors in H. pylori infection.

PMID- 16606981
TI  - Epidemiology and clinical aspects of enteric fever in Israel.
AB  - Enteric fever decreased in Israel in the last 50 years, but its current
      epidemiology is unknown. In a nationwide study, we evaluated all cases of enteric
      fever from 1995 to 2003. On hundred thirty-six cases met the case definition.
      During the period studied, the incidence of enteric fever decreased from 0.42 to
      0.23/100,000. A total of 57.4% of the cases were acquired abroad. The incidence
      of endemic enteric fever was 2.7 times higher in Arabs than in Jews. In Arabs,
      Salmonella Typhi was the causative agent in all cases, and almost all cases were
      endemic. In Jews, most cases were imported, with a decrease in imported S. typhi,
      cases and an increase in imported S. Paratyphi A cases. Salmonella Paratyphi B
      was endemic, and restricted to the Jewish population. The reasons for the
      difference in causative agents along ethnic lines need further evaluation. A more
      efficient vaccine for travelers that includes S. Paratyphi A is needed.

PMID- 16606982
TI  - Polymerase chain reaction and molecular genotyping to monitor parasitological
      response to anti-malarial chemotherapy in the Peruvian Amazon.
AB  - Over the past decade, anti-malarial drug resistance has rapidly become a major
      public health problem in the Peruvian Amazon. This study compared polymerase
      chain reaction (PCR) to light microscopy for diagnosing and monitoring the
      parasitological response of malaria patients to anti-malarial chemotherapy in the
      Peruvian Amazon region of Iquitos. Typing of P. falciparum using MSP1, MSP2, and
      glutamine-rich protein distinguished among infecting parasites. Most (73%) P.
      falciparum patients were parasitologically resistant to sulfadoxine-pyrimethamine
      (RI = 10, RII = 1). Sensitivity of microscopy was lower than PCR (69% for P.
      vivax and 78% for P. falciparum), but parasite clearance times were comparable
      between microscopy and PCR. PCR sensitively and specifically detected mixed
      infections and low-level parasitemia indicative of drug resistance, making this
      approach of practical use for the control of malaria at the public health level.
      Genotyping malaria parasites will be useful to distinguish drug failure from new
      infections in clinical trials of anti-malarial drugs in the Peruvian Amazon
      region.

PMID- 16606984
TI  - Malaria control in Henan Province, People's Republic of China.
AB  - We analyzed malaria prevalence and evaluated the effect of malaria control
      measures in Henan Province, People's Republic of China between 1993 and 2004.
      Data relating to malaria epidemics, malaria control measures and their effects,
      and vector surveillance between 1993 and 2004 were collected and analyzed. Mean
      malaria incidence during this period was 2.96/100,000. After integrated vector
      control measures and appropriate treatment of malaria cases were carried out, the
      number of malaria cases in Henan Province decreased from 4,815 in 2000 to 2,112
      in 2004. The parasite-positive rate and the density of Anopheles anthropophagus
      were also reduced. Malaria control measures were effective and malaria incidence
      decreased in Henan. However, there are still more cases in this province than in
      1992. Local malaria outbreaks and epidemics have occurred in areas where
      Anopheles anthropophagus and An. sinensis are present. Thus, malaria control
      measures should be strengthened.

PMID- 16606983
TI  - Low multiplication rates of African Plasmodium falciparum isolates and lack of
      association of multiplication rate and red blood cell selectivity with malaria
      virulence.
AB  - Two potential malaria virulence factors, parasite multiplication rate (PMR) and
      red blood cell selectivity (measured as selectivity index [SI]), were assessed in
      Plasmodium falciparum clinical isolates from Mali and Kenya. At both sites, PMRs
      were low (Kenya median = 2.2, n = 33; Mali median = 2.6, n = 61) and did not
      differ significantly between uncomplicated and severe malaria cases. Malian
      isolates from hyperparasitemic patients had significantly lower PMRs (median =
      1.8, n = 19) than other Malian isolates (uncomplicated malaria median = 3.1, n =
      23; severe malaria median = 2.8, n = 19; P = 0.03, by Kruskal-Wallis test).
      Selective invasion occurred at both sites (Kenya geometric mean SI = 1.9, n = 98;
      Mali geometric mean SI = 1.6, n = 104), and there was no significant association
      between the SI and malaria severity. Therefore, in contrast to previous results
      from Thailand, we found no association of PMR and SI with malaria severity in
      African children. This raises the possibility of differences in the mechanisms of
      malaria virulence between sub-Saharan Africa and Asia.

PMID- 16606985
TI  - Diagnosis of malaria by magnetic deposition microscopy.
AB  - Although malaria contributes to a significant public health burden, malaria
      diagnosis relies heavily on either non-specific clinical symptoms or blood smear
      microscopy methods developed in the 1930s. These approaches severely misrepresent
      the number of infected individuals and the reservoir of parasites in malaria
      endemic communities and undermine efforts to control disease. Limitations of
      conventional microscopy-based diagnosis center on time required to examine
      slides, time required to attain expertise sufficient to diagnose infection
      accurately, and attrition from the limited number of existing malaria microscopy
      experts. Earlier studies described magnetic properties of Plasmodium falciparum
      but did not refine methods to diagnosis infection by all four human malaria
      parasite species. Here, following specific technical procedures, we show that it
      is possible to concentrate all four human malaria parasite species, at least 40
      fold, on microscope slides using very inexpensive magnets through an approach
      termed magnetic deposition microscopy. This approach delivered greater
      sensitivity than a thick smear preparation while maintaining the clarity of a
      thin smear to simplify species-specific diagnosis. Because the magnetic force
      necessary to concentrate parasites on the slide is focused at a precise position
      relative to the magnet surface, it is possible to examine a specific region of
      the slide for parasitized cells and avoid the time-consuming process of scanning
      the entire slide surface. These results provide insight regarding new strategies
      for performing malaria blood smear microscopy.

PMID- 16606986
TI  - Association of FCgamma receptor IIA (CD32) polymorphism with malarial anemia and
      high-density parasitemia in infants and young children.
AB  - Protective immunity against Plasmodium falciparum is partially mediated through
      binding of malaria-specific IgG antibodies to Fcgamma receptors. Polymorphic
      variability in Fcgamma RIIa (H/R-131) is associated with differential binding of
      IgG subtypes and malaria disease outcomes. However, the role of Fcgamma RIIa-131
      variability in conditioning susceptibility to severe malarial anemia, the primary
      manifestation of severe malaria in holoendemic P. falciparum transmission areas,
      is largely undefined. Thus, Fcgamma RIIa-H131R polymorphism was investigated in
      493 children who came to a hospital with acute malaria. Variation in Fcgamma RIIa
      131 was not significantly associated with severe malarial anemia (hemoglobin [Hb]
      < 6.0 g/dL) or malaria anemia (Hb < 8.0 g/dL). However, relative to the
      heterozygous genotype, homozygotes for the R131 alleles were protected against
      high-density parasitemia (>or= 10,000 parasites/microL; odds ratio [OR] = 0.58,
      95% confidence interval [CI] = 0.37-0.92, P = 0.02), while homozygotes for the
      H131 alleles were mildly protective (OR = 0.71, 95% CI = 0.45-1.13, P = 0.14).
      Additional multivariate analyses showed that infection with human
      immunodeficiency virus type 1 did not influence the associations between
      FcgammaRIIa-H131R polymorphism and malaria disease outcomes. Genotypic results
      presented here parallel data illustrating that parasite density is unrelated to
      the severity of anemia in children with acute malaria. Thus, although
      homozygosity for the R131 allele protects against high-density parasitemia,
      FcgammaRIIa-131 polymorphism does not protect against malaria anemia.

PMID- 16606988
TI  - Stability of interferon-gamma and interleukin-10 responses to Plasmodium
      falciparum liver stage antigen-1 and thrombospondin-related adhesive protein in
      residents of a malaria holoendemic area.
AB  - The stability of anti-malarial immunity will influence the interpretation of
      immunologic endpoints during malaria vaccine trials conducted in endemic areas.
      Therefore, we evaluated cytokine responses to Plasmodium falciparum liver stage
      antigen-1 (LSA-1) and thrombospondin-related adhesive protein (TRAP) by Kenyans
      from a holoendemic area at a 9-month interval. The proportion of adults with
      interferon-gamma (IFN-gamma) responses to 9-mer LSA-1 peptides was similar at
      both time-points, whereas responses from children decreased (P < 0.05). Response
      to the longer, 23-mer LSA-1 peptide was variable, decreasing in adults and
      children over time (P < 0.02 and P < 0.001, respectively). The proportion of
      children with IFN-gamma responses to either antigen at the second time-point was
      significantly lower than that of adults, yet more adults responded to 9-mer TRAP
      peptides (P < 0.02). In contrast, the proportion of interleukin-10 responses to
      LSA-1 and TRAP was similar at both time-points for both age groups. Most
      noteworthy was that even when the repeat cross-sectional frequency of cytokine
      responses was the same, these responses were not generated by the same
      individuals. This suggests that cytokine responses to LSA-1 and TRAP are
      transient under natural exposure conditions.

PMID- 16606987
TI  - Frequencies of peripheral blood myeloid cells in healthy Kenyan children with
      alpha+ thalassemia and the sickle cell trait.
AB  - The high frequencies of both alpha+ thalassemia and the sickle cell trait
      (hemoglobin AS [HbAS]) found in many tropical populations are thought to reflect
      selection pressure from Plasmodium falciparum malaria. For HbAS, but not for
      alpha+ thalassemia, protection appears to be mediated by the enhanced phagocytic
      clearance of ring-infected erythrocytes. We have investigated the genotype
      specific distributions of peripheral blood leukocyte populations in two groups of
      children living on the coast of Kenya: a group of healthy P. falciparum parasite
      negative children sampled at cross-sectional survey during a period of low
      malaria transmission, and a group of children attending the hospital with acute
      malaria. We report distinctive distributions of peripheral blood myeloid
      dendritic cells and monocytes in children with alpha+ thalassemia and HbAS during
      healthy periods and disease, and suggest ways in which these might relate to the
      mechanisms of protection afforded by these conditions.

PMID- 16606989
TI  - Varicella zoster virus meningitis complicating sodium stibogluconate treatment
      for cutaneous leishmaniasis.
AB  - Sodium stibogluconate (Pentostam(R); GlaxoSmithKline) is a pentavalent antimonial
      compound used in the treatment of leishmaniasis, which has an association with
      reactivation of varicella zoster virus (VZV). We report the first known case of
      an immunocompetent adult who developed VZV aseptic meningitis and dermatomal
      herpes zoster during treatment with sodium stibogluconate.

PMID- 16606990
TI  - Short report: cloning of the Babesia gibsoni cytochrome B gene and isolation of
      three single nucleotide polymorphisms from parasites present after atovaquone
      treatment.
AB  - We determined the nucleotide sequence of the Babesia gibsoni cytochrome b (cytb)
      gene. DNA was extracted from B. gibsoni isolated from Aomori Prefecture, Japan,
      and 1,288 basepairs of the cytb gene, including 1,071 basepairs of the open
      reading frame, were sequenced. The cytb gene of B. gibsoni obtained from three
      dogs that had been experimentally infected with B. gibsoni and treated with
      atovaquone was also sequenced. The B. gibsoni cytb gene obtained from all three
      atovaquone-treated dogs contained a single polymorphism resulting in an amino
      acid change in one of the putative ubiquinone-binding sites of Plasmodium
      falciparum. This polymorphism was homologous to mutations in other apicomplexan
      protozoa that exhibit resistance to atovaquone. Two other single polymorphisms
      were identified in parasites isolated from two of the dogs. These results
      indicate that single nucleotide polymorphisms in the sequence for mitochondrial
      cytb gene may be associated with decreased susceptibility of Babesia species to
      atovaquone.

PMID- 16606991
TI  - Short report: cysticercosis in an Egyptian mummy of the late Ptolemaic period.
AB  - We describe here an ancient case of cysticercosis that was discovered in an
      Egyptian mummy of a young woman of about 20 years of age who lived in the late
      Ptolemaic period (second to first centuries b.c.). On removal of the stomach and
      its rehydration, a cystic lesion in the stomach wall was observed by naked eye.
      Microscopical examination of sections of this lesion revealed a cystic structure,
      with a wall, with numerous projecting eversions, a characteristic feature of the
      larval stage (cysticercus) of the human tapeworm Taenia solium (or "pig
      tapeworm"). Immunohistochemical testing with serum from a T. solium-infected
      human confirmed the identity of the cyst. This finding is the oldest on record of
      the antiquity of this zoonotic parasite. This observation also confirms that, in
      Hellenistic Egypt, the farming of swine, along with man an intermediate host of
      this parasite, was present, and supports other archeological evidence.

PMID- 16606992
TI  - Risk factors for death in acquired immunodeficiency syndrome-associated
      disseminated histoplasmosis.
AB  - We performed a retrospective study of 164 human immunodeficiency virus (HIV)
      infected patients with disseminated histoplasmosis to identify the risk factors
      for death. Death occurred in 32% of the cases. Univariate analysis identified the
      following risk factors: diarrhea (odds ratio [OR] = 3.9, P = 0.001), neurologic
      manifestations (OR = 5.8, ; P = 0.001), hemoglobin level < 8.0g/dL (OR = 2.7, P =
      0.004), urea level 2 times the normal upper limit (OR = 5.0, P < 0.001),
      creatinine level > 1.5 mg/dL (OR = 2.9, P = 0.005), aspartate aminotransferase
      (AST) level > 2.5 times the normal upper limit (OR = 3.1, P = 0.01), respiratory
      insufficiency (OR = 9.7, P < 0.001), sepsis (OR = 20.2, P < 0.001), and acute
      renal failure (OR = 2.5, P = 0.011). A hemoglobin level < 8.0 g/dL (OR = 3.8, P =
      0.008), an AST level >or= 2.5 times the normal limit (OR = 1.0, P = 0.007), acute
      renal failure (OR = 2.96, P = 0.015), and respiratory insufficiency (OR = 12.2, P
      = 0.01) were independent risk factors for death.

PMID- 16606993
TI  - Association between tuberculosis and diabetes in the Mexican border and non
      border regions of Texas.
AB  - The association between tuberculosis and underlying risk factors was evaluated in
      Texas patients hospitalized in the 15 counties along the Mexico border within the
      remaining non-border counties. A case control analysis of the hospital discharge
      dataset from the Texas Health Care Information Council was performed for the
      years 1999-2001. A discharge diagnosis of tuberculosis identified cases (N =
      4,915). Deep venous thrombosis, pulmonary embolism, and acute appendicitis
      conditions identified controls (N = 70,808). Risk factors associated with
      tuberculosis were identified by logistic regression. Diabetes patients were
      almost twice as likely to have tuberculosis after adjusting by sex, age, and
      race/ethnicity. The association was strong for the population in the Texas border
      region, where there are higher incidence rates of tuberculosis (odds ratio
      [OR](adj) = 1.82; 95% CI = 1.57-2.12) compared with non-border counties (OR(adj)
      = 1.51; 95% CI = 1.36-1.67).

PMID- 16606994
TI  - Short report: dual infections with Puumala virus and Leptospira interrogans
      serovar lora in a bank vole (Clethrionomys glareolus).
AB  - Leptospirosis and hemorrhagic fever with renal syndrome are public health
      problems in Croatia. Diagnosis and epidemiology of these diseases are complicated
      because these two diseases are sympatric in certain areas. We describe a natural
      dual infection of Puumala virus and a leptospire in a bank vole (Clethrionomys
      glareolus).

PMID- 16606995
TI  - A modest model explains the distribution and abundance of Borrelia burgdorferi
      strains.
AB  - The distribution and abundance of Borrelia burgdorferi, including human Lyme
      disease strains, is a function of its interactions with vertebrate species. We
      present a mathematical model describing important ecologic interactions affecting
      the distribution and abundance of B. burgdorferi strains, marked by the allele at
      the outer surface protein C locus, in Ixodes scapularis ticks, the principal
      vector. The frequency of each strain in ticks can be explained by the vertebrate
      species composition, the density of each vertebrate species, the number of ticks
      that feed on individuals of each species, and the rate at which those ticks
      acquire different strains. The model results are consistent with empirical data
      collected in a major Lyme disease focus in New England. An applicable extension
      of these results would be to predict the proportion of ticks carrying human
      infectious strains of B. burgdorferi from disease host densities and thus predict
      the local risk of contracting Lyme disease.

PMID- 16606996
TI  - Human Campylobacter-associated enteritis on the Caribbean island of Barbados.
AB  - A longitudinal study of the incidence of Campylobacter enteritis in Barbados was
      undertaken from January 2000 to August 2003. Diarrheal stools received by the
      central public health laboratory were cultured for Campylobacter. The number of
      reported Campylobacter cases exceeded those of Shigella but were less than those
      of Salmonella, and increased steadily with each year. Isolates from stools were
      mainly C. jejuni (63.6%) and C. coli (31.8%). The highest isolation rate was
      found in children 1-4 years of age (40.8%), followed by infants less than 1 year
      of age (16.9%) and those 5-9 years of age (11.3%). The number of reported cases
      was higher in March, from June to August, and in November and December. There was
      no correlation between incidence and either rainfall, temperature, or humidity.
      Further epidemiologic investigation of this disease is needed to evaluate risk
      factors for Campylobacter infection and determine routes of transmission in
      Barbados.

PMID- 16606997
TI  - Wound botulism acquired in the Amazonian rain forest of Ecuador.
AB  - Wound botulism results from colonization of a contaminated wound by Clostridium
      botulinum and the anaerobic in situ production of a potent neurotoxin. Between
      1943, when wound botulism was first recognized, and 1990, 47 laboratory-confirmed
      cases, mostly trauma-associated, were reported in the United States. Since 1990,
      wound botulism associated with injection drug use emerged as the leading cause of
      wound botulism in the United States; 210 of 217 cases reported to the Centers for
      Disease Control and Prevention between 1990 and 2002 were associated with drug
      injection. Despite the worldwide distribution of Clostridium botulinum spores,
      wound botulism has been reported only twice outside the United States, Europe,
      and Australia. However, wound botulism may go undiagnosed and untreated in many
      countries. We report two cases, both with type A toxin, from the Ecuadorian rain
      forest. Prompt clinical recognition, supportive care, and administration of
      trivalent equine botulinum antitoxin were life-saving.

PMID- 16606998
TI  - Predicting density of Ixodes pacificus nymphs in dense woodlands in Mendocino
      County, California, based on geographic information systems and remote sensing
      versus field-derived data.
AB  - Ixodes pacificus nymphs are the primary vectors to humans of Borrelia
      burgdorferi, the etiologic agent of Lyme disease, in California. We used a
      supervised classification model, based on remote sensing (RS) data from multi
      seasonal Landsat TM 5 images, to identify the key habitat in Mendocino County
      where humans are exposed to I. pacificus nymphs (woodlands carpeted with leaf
      litter). The model, based on the normalized difference vegetation index (NDVI),
      brightness, and wetness, separated the nymphal risk habitat (52.6% of the county)
      from other habitat types with > 93% user and producer accuracies. Next, we
      determined the density of questing nymphs in 62 woodland-leaf areas located
      throughout Mendocino County and created forward-stepwise regression models
      explaining the variation in nymphal density based on traits attainable by a lay
      person in the field (e.g., tree species present, deer signs; r(2) = 0.43, P <
      0.0001), or geographic information systems (GIS)/RS-based environmental data
      (r(2) = 0.50, P < 0.0001). The GIS/RS model, using July NDVI, November greenness,
      a coastal influence category, May solar insolation, November hours of sunlight,
      and dominant hydrologic grouping as input variables, was 22% more accurate in
      predicting nymphal density at 16 validation sites (r(2) = 0.72) than the field
      derived data model (r(2) = 0.50). The habitat classification and GIS/RS models
      were combined to create a continuous nymphal density surface for the entirety of
      Mendocino County. This risk surface showed that 11.9% of the county was
      classified as habitat posing at least moderate risk of human exposure to nymphs
      (> 6.4 nymphs per 100 m(2)). Furthermore, high-risk areas (> 10.5 nymphs per 100
      m(2); 1.7% of the county) tended to cluster in the central interior and most
      heavily populated region of Mendocino County, but were rare in the proximity of
      coastal population centers.

PMID- 16606999
TI  - Genetic differentiation between the BAMAKO and SAVANNA chromosomal forms of
      Anopheles gambiae as indicated by amplified fragment length polymorphism
      analysis.
AB  - The main vector of malaria in sub-Saharan Africa, Anopheles gambiae, is
      subdivided into five chromosomal forms. Three of them (i.e., BAMAKO, SAVANNA, and
      MOPTI) are found in sympatry in Mali, where MOPTI can be distinguished from the
      other two forms based on differences in the ribosomal DNA locus. However, no
      molecular markers are available to distinguish BAMAKO from SAVANNA. We examined
      the banding patterns of 139 amplified fragment length polymorphism primer
      combinations in an attempt to identify diagnostic differences between SAVANNA and
      BAMAKO. Despite screening > 10,000 bands, no diagnostic differences were found.
      However, additional AFLP analyses indicated that BAMAKO is genetically
      differentiated from SAVANNA, with a significant Phi(st) value of 0.072. This
      could indicate that gene flow between these forms is restricted in at least some
      portion of the genome and the lack of identifiable fixed differences between the
      two forms is probably due to their recent origin.

PMID- 16607000
TI  - PCR-based assay to survey for knockdown resistance to pyrethroid acaricides in
      human scabies mites (Sarcoptes scabiei var hominis).
AB  - Permethrin, in the form of a topical cream, is being increasingly used for
      community-based programs to control endemic scabies. The development of
      resistance has reduced the use of pyrethroids for the control of many arthropods
      of economic and health importance. The best recognized form of pyrethroid
      resistance, known as knockdown resistance or kdr, has been linked to specific
      mutations in the target of these agents, the para-homologous voltage-sensitive
      sodium channel gene (Vssc). To develop tools to study resistance to pyrethroid
      acaricides, we cloned 3711 and 6151 bp, respectively, of cDNA and genomic
      fragments of the Vssc gene from scabies mite, Sarcoptes scabiei. The sequence
      encompasses the major polymorphic amino acid residues associated with pyrethroid
      resistance. A polymerase chain reaction-based strategy has been developed that
      enables genotyping individual scabies mites. This will facilitate early detection
      and monitoring of pyrethroid resistance in scabies mite populations under drug
      selection pressure.

PMID- 16607001
TI  - A new high-performance PCR diagnostic for the detection of pyrethroid knockdown
      resistance kdr in Anopheles gambiae.
AB  - Monitoring the spread of the knockdown resistance allele kdr in areas of
      extensive pyrethroid use is critical to vector-control projects. Currently
      available methods for detecting kdr from DNA samples are characterized by poor
      amplification, time-consuming steps, and primers that exhibit frequent null
      alleles. We describe a new PCR diagnostic that uses fluorescent primers based on
      conserved priming sites and enables simple detection of the kdr allele on a
      sequencer. Using samples from a West African Anopheles gambiae population, we
      show that the new PCR yielded significantly higher rates of amplification and
      more accurate estimates of kdr frequency. The method works equally well for the
      leucine to phenylalanine substitution found in West Africa and the East African
      leucine to serine substitution.

PMID- 16607002
TI  - Determinants of vector specificity of o'nyong nyong and chikungunya viruses in
      Anopheles and Aedes mosquitoes.
AB  - The alphaviruses o'nyong nyong virus (ONNV) and chikungunya virus (CHIKV) provide
      a unique system to study the viral genes involved in vector specificity. ONNV
      infects both anopheline and culicine mosquitoes, whereas CHIKV infects only
      culicine mosquitoes. In this study, chimeric viruses were constructed that
      contained genes from both ONNV and CHIKV. These chimeras and previously described
      full-length infectious clones of ONNV and CHIKV were evaluated in Anopheles
      gambiae and Aedes aegypti mosquitoes. Virus derived from the infectious clones of
      ONNV and CHIKV retained the vector specificity of the parental viruses. All six
      of the chimeras were found to infect Ae. aegypti mosquitoes at high rates but
      only the chimera containing viral genes encoding all of the structural proteins
      of ONNV was able to infect An. gambiae mosquitoes. These data indicate that all
      of the viral structural proteins are necessary for ONNV to infect An. gambiae
      mosquitoes.

PMID- 16607003
TI  - Pathogenesis of West Nile virus infection in dogs treated with glucocorticoids.
AB  - Control and glucocorticoid-treated dogs were infected with West Nile virus (WNV)
      through the bites of infected mosquitoes to study the effect of a commonly used
      immunomodulator on the magnitude and duration of viremia and on development of
      clinical disease. All dogs became viremic after challenge. The peak viremia and
      integrated magnitude of viremia were approximately 40 and 50 times higher,
      respectively, in the five dogs treated with methyl-prednisolone for 1 month
      compared with untreated dogs. None of the five control or treated dogs developed
      signs of clinical disease, nor was histopathologic evidence of neuroinvasion
      observed in any case. Neutralizing antibodies to WNV were produced in all dogs,
      with no apparent effect of glucocorticoid treatment. Considering the dramatic
      effect of glucocorticoid treatment on magnitude of viremia, it is likely that
      this therapy had suppressive effects on some aspect of innate immunity or T cell
      function.

PMID- 16607004
TI  - Molecular epidemiology of human immunodeficiency virus-infected individuals in
      Medellin, Colombia.
AB  - To study the molecular epidemiology of human immunodeficiency virus type 1 (HIV
      1) strains in Medellin, Colombia, 115 HIV-1-positive individuals who were
      recruited from an HIV outpatient hospital (Universitario San Vicente de Paul)
      during the period from July 2001 to January 2002 were genotyped. All samples were
      analyzed by envelope heteroduplex mobility assay and found to be subtype B.
      Twenty-four samples were randomly selected for sequencing of the protease and the
      reverse transcriptase regions; all isolates were found to be subtype B.
      Phylogenetic analysis of seven nearly full-length genomes showed that all samples
      were subtype B. This study shows that the HIV epidemic in Colombia continues to
      be dominated by the subtype B virus. The predominance of subtype B genotypes of
      HIV-1 strains in Medellin resembles what is seen in the nearby countries of Peru,
      Ecuador, and Venezuela.

PMID- 16607005
TI  - Human and mosquito infections by dengue viruses during and after epidemics in a
      dengue-endemic region of Colombia.
AB  - We conducted a study in a dengue-endemic area of Colombia to evaluate the
      dynamics of transmission of dengue viruses during and after epidemics.
      Information was simultaneously gathered about occurrence of infection in humans
      and mosquitoes every three months in four cities with endemic transmission. Viral
      isolation was confirmed in 6.7% of the persons and most were asymptomatic. Adult
      mosquito and larvae house indexes were not found associated with increased burden
      of disease. The only entomologic indicator related to dengue infection in humans
      was the pooled infection rate of mosquitoes. Aedes aegypti infection rates showed
      significant differences between the epidemic (10.68, 95% confidence interval [CI]
      = 7.04-15.62) and after epidemic periods of the study (6.15, 95% CI = 3.46
      10.19). In addition, Ae. albopictus were also infected with dengue viruses.
      Increases in mosquito infection rates were associated with increases in human
      infection rates in the following trimester.

PMID- 16607006
TI  - Volume replacement in infants with dengue hemorrhagic fever/dengue shock
      syndrome.
AB  - Volume replacement was studied prospectively in 208 infants with dengue
      hemorrhagic fever/dengue shock syndrome (DHF/DSS). The mean volume of intravenous
      fluid used was 110.4 mL/kg administered over a mean period of 25.8 hours. The
      mean volumes of intravenous fluid replacement in infants with DSS was
      significantly higher than in those with non-shock DHF (129.8 mL/kg versus 102.1
      mL/kg; P = 0.001). Patients with DSS had significantly higher proportional
      requirements for dextran and blood transfusions than non-shock infants. Recurrent
      shock, prolonged shock, and acute respiratory failure were recorded in 8, 6, and
      13 patients, respectively. Four patients with DSS died of severe complications.
      Intravenous fluid replacement with special care to avoid fluid overload requires
      careful attention to established indications for use of colloidal solutions and
      blood transfusions. To improve case fatality rates, special efforts need to be
      directed to infants with DHF/DSS accompanied by severe complications.

PMID- 16607007
TI  - Dengue knowledge and practices and their impact on Aedes aegypti populations in
      Kamphaeng Phet, Thailand.
AB  - A knowledge, attitude, and practice (KAP) survey and an extensive entomologic
      survey were conducted in two sub-districts of Kamphaeng Phet province, Thailand,
      to test the hypothesis that correct dengue knowledge and practice reduce dengue
      vector populations. We found a negative association between respondents'
      knowledge of preventive measures and the number of unprotected containers in and
      around their houses. Knowledge of development sites was positively associated
      with unprotected containers. No relationships existed between knowledge of dengue
      and adult mosquito reduction practices. A higher number of unprotected containers
      increased the likelihood of the house being infested with one or more adult Aedes
      aegypti. Surprisingly, houses of respondents that used mosquito coils or had
      screening on doors and windows were significantly more likely to be infested
      (odds ratio =2.0) with adult Ae. aegypti. We conclude that there is a direct link
      between knowledge on dengue prevention and container protection practices,
      whereas measures against adult mosquitoes are used only when people experience a
      mosquito nuisance problem.

PMID- 16607008
TI  - Talking to themselves: autoregulation and quorum sensing in fungi.

PMID- 16607009
TI  - Regulatory domains of Snf1-activating kinases determine pathway specificity.
AB  - In Saccharomyces cerevisiae, the Snf1 kinase can be activated by any one of three
      upstream kinases, Sak1, Tos3, or Elm1. All three Snf1-activating kinases contain
      serine/threonine kinase domains near their N termini and large C-terminal domains
      with little sequence conservation and previously unknown function. Deletion of
      the C-terminal domains of Sak1 and Tos3 greatly reduces their ability to activate
      the Snf1 pathway. In contrast, deletion of the Elm1 C-terminal domain has no
      effect on Snf1 signaling but abrogates the ability of Elm1 to participate in the
      morphogenetic-checkpoint signaling pathway. Thus, the C-terminal domains of Sak1,
      Tos3, and Elm1 help to determine pathway specificity. Additional deletion mutants
      of the Sak1 kinase revealed that the N terminus of the protein is essential for
      Snf1 signaling. The deletion of 43 amino acids from within the N terminus of Sak1
      (residues 87 to 129) completely blocks Snf1 signaling and activation loop
      phosphorylation in vivo. The Sak1 kinase domain (lacking both N-terminal and C
      terminal domains) is catalytically active and specific in vitro but is unable to
      promote Snf1 signaling in vivo when expressed at normal levels. Our studies
      indicate that the kinase domains of the Snf1-activating kinases are not
      sufficient by themselves for their proper function and that the nonconserved N
      terminal and C-terminal domains are critical for the biological activities of
      these kinases.

PMID- 16607010
TI  - Composition-modified matrices improve identification of homologs of saccharomyces
      cerevisiae low-complexity glycoproteins.
AB  - Yeast glycoproteins are representative of low-complexity sequences, those
      sequences rich in a few types of amino acids. Low-complexity protein sequences
      comprise more than 10% of the proteome but are poorly aligned by existing
      methods. Under default conditions, BLAST and FASTA use the scoring matrix
      BLOSUM62, which is optimized for sequences with diverse amino acid compositions.
      Because low-complexity sequences are rich in a few amino acids, these tools tend
      to align the most common residues in nonhomologous positions, thereby generating
      anomalously high scores, deviations from the expected extreme value distribution,
      and small e values. This anomalous scoring prevents BLOSUM62-based BLAST and
      FASTA from identifying correct homologs for proteins with low-complexity
      sequences, including Saccharomyces cerevisiae wall proteins. We have devised and
      empirically tested scoring matrices that compensate for the overrepresentation of
      some amino acids in any query sequence in different ways. These matrices were
      tested for sensitivity in finding true homologs, discrimination against
      nonhomologous and random sequences, conformance to the extreme value
      distribution, and accuracy of e values. Of the tested matrices, the two best
      matrices (called E and gtQ) gave reliable alignments in BLAST and FASTA searches,
      identified a consistent set of paralogs of the yeast cell wall test set proteins,
      and improved the consistency of secondary structure predictions for cell wall
      proteins.

PMID- 16607011
TI  - Conserved fungal genes as potential targets for broad-spectrum antifungal drug
      discovery.
AB  - The discovery of novel classes of antifungal drugs depends to a certain extent on
      the identification of new, unexplored targets that are essential for growth of
      fungal pathogens. Likewise, the broad-spectrum capacity of future antifungals
      requires the target gene(s) to be conserved among key fungal pathogens. Using a
      genome comparison (or concordance) tool, we identified 240 conserved genes as
      candidates for potential antifungal targets in 10 fungal genomes. To facilitate
      the identification of essential genes in Candida albicans, we developed a
      repressible C. albicans MET3 (CaMET3) promoter system capable of evaluating gene
      essentiality on a genome-wide scale. The CaMET3 promoter was found to be highly
      amenable to controlled gene expression, a prerequisite for use in target-based
      whole-cell screening. When the expression of the known antifungal target C.
      albicans ERG1 was reduced via down-regulation of the CaMET3 promoter, the CaERG1
      conditional mutant strain became hypersensitive, specifically to its inhibitor,
      terbinafine. Furthermore, parallel screening against a small compound library
      using the CaERG1 conditional mutant under normal and repressed conditions
      uncovered several hypersensitive compound hits. This work therefore demonstrates
      a streamlined process for proceeding from selection and validation of candidate
      antifungal targets to screening for specific inhibitors.

PMID- 16607012
TI  - Low genetic variation and no detectable population structure in aspergillus
      fumigatus compared to closely related Neosartorya species.
AB  - Aspergillus fumigatus is an anamorphic euascomycete mold with a ubiquitous
      presence worldwide. Despite intensive work to understand its success as a
      pathogen infecting immunosuppressed patients, the population dynamics and recent
      evolutionary history of A. fumigatus remain understudied. We examined patterns of
      genetic variation at three intergenic loci for 70 natural isolates from Europe,
      North America, South America, Asia, Africa, and Australia. The same loci were
      used to analyze within-population genetic variation for 33 isolates obtained from
      five geographic locations. Neither data set detected evidence of population
      differentiation or found any association between the genetic and geographic
      distances among these isolates. No evidence for genetic differentiation within
      the two A. fumigatus mating types was detected. The genetic diversity of A.
      fumigatus, contrasted with that of its close teleomorphic relatives, Neosartorya
      fischeri and Neosartorya spinosa, is remarkably low.

PMID- 16607013
TI  - The C-module DNA-binding factor mediates expression of the dictyostelium
      aggregation-specific adenylyl cyclase ACA.
AB  - Aggregation of Dictyostelium discoideum amoebae into multicellular structures is
      organized by cyclic AMP (cAMP), which acts as a chemoattractant, as a second
      messenger, and as a morphogen. Aggregation of D. discoideum cells depends on the
      expression of adenylyl cyclase ACA, which provides extracellular cAMP for signal
      relay and intracellular cAMP for the induction of genes required at multicellular
      stages. We have identified a DNA-binding activity specific for a highly A+T
      enriched motif in the upstream region of the ACA-encoding gene, acaA. The factor
      shows DNA-binding characteristics very similar to those of C-module-binding
      factor (CbfA). Although CbfA was originally identified as a putative regulator of
      the activity of D. discoideum retrotransposon TRE5-A, it also was found to be
      essential for aggregation of D. discoideum cells. The identified DNA-binding
      activity was absent in mutant cells depleted of CbfA, and CbfA could be
      precipitated using an acaA promoter fragment. We propose that CbfA binds to the
      acaA promoter to provide a basal transcription activity that is required for
      induction of ACA expression after the onset of D. discoideum development.

PMID- 16607014
TI  - Acanthamoeba castellanii promotion of in vitro survival and transmission of
      coxsackie b3 viruses.
AB  - This work was undertaken to determine whether Acanthamoeba could play a role in
      the survival and transmission of coxsackieviruses and focused on in vitro
      interactions between Acanthamoeba castellanii and coxsackie B3 viruses (CVB-3).
      Residual virus titer evaluations and immunofluorescence experiments revealed a
      remarkable CVB-3 adsorption on amoeba surfaces and accumulation inside cells. The
      survival of viruses was independent of the dynamics of amoeba replication and
      encystment. In addition, our results indicated that virus-infected amoebas can
      release infectious viruses during interaction with human macrophages. On the
      basis of these data, Acanthamoeba appears to be a potential promoter of the
      survival of coxsackieviruses and their transmission to human hosts.

PMID- 16607015
TI  - High-mobility-group box nuclear factors of Plasmodium falciparum.
AB  - In eukaryotes, the high-mobility-group (HMG) nuclear factors are highly conserved
      throughout evolution and are divided into three families, including HGMB,
      characterized by an HMG box domain. Some HMGB factors are DNA structure specific
      and preferentially interact with distorted DNA sequences, trigger DNA bending,
      and hence facilitate the binding of nucleoprotein complexes that in turn activate
      or repress transcription. In Plasmodium falciparum, two HMGB factors were
      predicted: PfHMGB1 and PfHMGB2. They are small proteins, under 100 amino acids
      long, encompassing a characteristic HMG box domain closely related to box B of
      metazoan factors, which comprises two HMG box domains, A and B, in tandem.
      Computational analyses supported the conclusion that the Plasmodium proteins were
      genuine architectural HMGB factors, and in vitro analyses performed with both
      recombinant proteins established that they were able to interact with distorted
      DNA structures and bend linear DNA with different affinities. These proteins were
      detected in both asexual- and gametocyte-stage cells in Western blotting
      experiments and mainly in the parasite nuclei. PfHMGB1 is preferentially
      expressed in asexual erythrocytic stages and PfHMGB2 in gametocytes, in good
      correlation with transcript levels of expression. Finally, immunofluorescence
      studies revealed differential subcellular localizations: both factors were
      observed in the nucleus of asexual- and sexual-stage cells, and PfHMGB2 was also
      detected in the cytoplasm of gametocytes. In conclusion, in light of differences
      in their levels of expression, subcellular localizations, and capacities for
      binding and bending DNA, these factors are likely to play nonredundant roles in
      transcriptional regulation of Plasmodium development in erythrocytes.

PMID- 16607016
TI  - Ras GTPase-activating protein gap1 of the homobasidiomycete Schizophyllum commune
      regulates hyphal growth orientation and sexual development.
AB  - The white rot fungus Schizophyllum commune is used for the analysis of mating and
      sexual development in homobasidiomycete fungi. In this study, we isolated the
      gene gap1 encoding a GTPase-activating protein for Ras. Disruption of gap1 should
      therefore lead to strains accumulating Ras in its activated, GTP-bound state and
      to constitutive Ras signaling. Haploid Deltagap1 monokaryons of different mating
      types did not show alterations in mating behavior in the four different mating
      interactions possible in fungi expressing a tetrapolar mating type system.
      Instead, the growth rate in Deltagap1 monokaryons was reduced by ca. 25% and ca.
      50% in homozygous Deltagap1/Deltagap1 dikaryons. Monokaryons, as well as
      homozygous dikaryons, carrying the disrupted gap1 alleles exhibited a
      disorientated growth pattern. Dikaryons showed a strong phenotype during clamp
      formation since hook cells failed to fuse with the peg beside them. Instead, the
      dikaryotic character of the hyphae was rescued by fusion of the hooks with nearby
      developing branches. Deltagap1/Deltagap1 dikaryons formed increased numbers of
      fruitbody primordia, whereas the amount of fruitbodies was not raised. Mature
      fruitbodies formed no or abnormal gills. No production of spores could be
      observed. The results suggest Ras involvement in growth, clamp formation, and
      fruitbody development.

PMID- 16607017
TI  - Flagellar motility contributes to cytokinesis in Trypanosoma brucei and is
      modulated by an evolutionarily conserved dynein regulatory system.
AB  - The flagellum of Trypanosoma brucei is a multifunctional organelle with critical
      roles in motility and other aspects of the trypanosome life cycle. Trypanin is a
      flagellar protein required for directional cell motility, but its molecular
      function is unknown. Recently, a trypanin homologue in Chlamydomonas reinhardtii
      was reported to be part of a dynein regulatory complex (DRC) that transmits
      regulatory signals from central pair microtubules and radial spokes to axonemal
      dynein. DRC genes were identified as extragenic suppressors of central pair
      and/or radial spoke mutations. We used RNA interference to ablate expression of
      radial spoke (RSP3) and central pair (PF16) components individually or in
      combination with trypanin. Both rsp3 and pf16 single knockdown mutants are
      immotile, with severely defective flagellar beat. In the case of rsp3, this loss
      of motility is correlated with the loss of radial spokes, while in the case of
      pf16 the loss of motility correlates with an aberrant orientation of the central
      pair microtubules within the axoneme. Genetic interaction between trypanin and
      PF16 is demonstrated by the finding that loss of trypanin suppresses the pf16
      beat defect, indicating that the DRC represents an evolutionarily conserved
      strategy for dynein regulation. Surprisingly, we discovered that four independent
      mutants with an impaired flagellar beat all fail in the final stage of
      cytokinesis, indicating that flagellar motility is necessary for normal cell
      division in T. brucei. These findings present the first evidence that flagellar
      beating is important for cell division and open the opportunity to exploit
      enzymatic activities that drive flagellar beat as drug targets for the treatment
      of African sleeping sickness.

PMID- 16607018
TI  - Endoplasmic reticulum-associated degradation is required for cold adaptation and
      regulation of sterol biosynthesis in the yeast Saccharomyces cerevisiae.
AB  - Endoplasmic reticulum-associated degradation (ERAD) mediates the turnover of
      short-lived and misfolded proteins in the ER membrane or lumen. In spite of its
      important role, only subtle growth phenotypes have been associated with defects
      in ERAD. We have discovered that the ERAD proteins Ubc7 (Qri8), Cue1, and Doa10
      (Ssm4) are required for growth of yeast that express high levels of the sterol
      biosynthetic enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR).
      Interestingly, the observed growth defect was exacerbated at low temperatures,
      producing an HMGR-dependent cold sensitivity. Yeast strains lacking UBC7, CUE1,
      or DOA10 also assembled aberrant karmellae (ordered arrays of membranes
      surrounding the nucleus that assemble when HMGR is expressed at high levels).
      However, rather than reflecting the accumulation of abnormal karmellae, the cold
      sensitivity of these ERAD mutants was due to increased HMGR catalytic activity.
      Mutations that compromise proteasomal function also resulted in cold-sensitive
      growth of yeast with elevated HMGR, suggesting that improper degradation of ERAD
      targets might be responsible for the observed cold-sensitive phenotype. However,
      the essential ERAD targets were not the yeast HMGR enzymes themselves. The sterol
      metabolite profile of ubc7Delta cells was altered relative to that of wild-type
      cells. Since sterol levels are known to regulate membrane fluidity, the viability
      of ERAD mutants expressing normal levels of HMGR was examined at low
      temperatures. Cells lacking UBC7, CUE1, or DOA10 were cold sensitive, suggesting
      that these ERAD proteins have a role in cold adaptation, perhaps through effects
      on sterol biosynthesis.

PMID- 16607019
TI  - Phosphoinositide 5-phosphatase Fig 4p is required for both acute rise and
      subsequent fall in stress-induced phosphatidylinositol 3,5-bisphosphate levels.
AB  - Phosphoinositide lipids regulate complex events via the recruitment of proteins
      to a specialized region of the membrane at a specific time. Precise control of
      both the synthesis and turnover of phosphoinositide lipids is integral to
      membrane trafficking, signal transduction, and cytoskeletal rearrangements.
      Little is known about the acute regulation of the levels of these signaling
      lipids. When Saccharomyces cerevisiae cells are treated with hyperosmotic medium
      the levels of phosphatidylinositol 3,5-bisphosphate (PI3,5P(2)) increase 20-fold.
      Here we show that this 20-fold increase is rapid and occurs within 5 min.
      Surprisingly, these elevated levels are transient. Fifteen minutes following
      hyperosmotic shock they decrease at a rapid rate, even though the cells remain in
      hyperosmotic medium. In parallel with the rapid increase in the levels of
      PI3,5P(2), vacuole volume decreases rapidly. Furthermore, concomitant with a
      return to basal levels of PI3,5P(2) vacuole volume is restored. We show that Fig
      4p, consistent with its proposed role as a PI3,5P(2) 5-phosphatase, is required
      in vivo for this rapid return to basal levels of PI3,5P(2). Surprisingly, we find
      that Fig 4p is also required for the hyperosmotic shock-induced increase in
      PI3,5P(2) levels. These findings demonstrate that following hyperosmotic shock,
      large, transient changes occur in the levels of PI3,5P(2) and further suggest
      that Fig 4p is important in regulating both the acute rise and subsequent fall in
      PI3,5P(2) levels.

PMID- 16607020
TI  - Targeted gene silencing in the model mushroom Coprinopsis cinerea (Coprinus
      cinereus) by expression of homologous hairpin RNAs.
AB  - The ink cap Coprinopsis cinerea is a model organism for studying fruiting body
      (mushroom) formation in homobasidiomycetes. Mutant screens and expression studies
      have implicated a number of genes in this developmental process. Functional
      analysis of these genes, however, is hampered by the lack of reliable reverse
      genetics tools for C. cinerea. Here, we report the applicability of gene
      targeting by RNA silencing for this organism. Efficient silencing of both an
      introduced GFP expression cassette and the endogenous cgl1 and cgl2 isogenes was
      achieved by expression of homologous hairpin RNAs. In latter case, silencing was
      the result of a hairpin construct containing solely cgl2 sequences, demonstrating
      the possibility of simultaneous silencing of whole gene families by a single
      construct. Expression of the hairpin RNAs reduced the mRNA levels of the target
      genes by at least 90%, as determined by quantitative real-time PCR. The reduced
      mRNA levels were accompanied by cytosine methylation of transcribed and
      nontranscribed DNA at both silencing and target loci in the case of constitutive
      high-level expression of the hairpin RNA but not in the case of transient
      expression. These results suggest the presence of both posttranscriptional and
      transcriptional gene silencing mechanisms in C. cinerea and demonstrate the
      applicability of targeted gene silencing as a powerful reverse genetics approach
      in this organism.

PMID- 16607021
TI  - Activation of zoosporogenesis-specific genes in Phytophthora infestans involves a
      7-nucleotide promoter motif and cold-induced membrane rigidity.
AB  - Infections of plants by the oomycete Phytophthora infestans typically result from
      zoospores, which develop from sporangia at cold temperatures. To help understand
      the relevant cold-induced signaling pathway, factors regulating the transcription
      of the zoosporogenesis-specific NIF (nuclear LIM-interactor-interacting factor)
      gene family were examined. Sequences required for inducing PinifC3 were
      identified by analyzing truncated and mutated promoters using the beta
      glucuronidase reporter in stable transformants. A 7-nucleotide (nt) sequence
      located 139 bases upstream of the major transcription start point (GGACGAG)
      proved essential for the induction of PinifC3 when sporangia were shifted from
      ambient to cold temperatures. The motif, named the cold box, also conferred cold
      inducibility to a promoter normally activated only during sexual development. An
      identical motif was detected in the two other zoosporogenesis-specific NIF genes
      from P. infestans and three Phytophthora sojae orthologues, and a closely related
      sequence was found in Phytophthora ramorum orthologues. The 7-nt motif was also
      found in the promoters of other zoosporogenesis-induced genes. The presence of a
      cold box-interacting protein in nuclear extracts of P. infestans sporangia was
      demonstrated using electrophoretic mobility shift assays. Furthermore, zoospore
      release and cold box-regulated transcription were stimulated by the membrane
      rigidizer dimethyl sulfoxide and inhibited by the membrane fluidizer benzyl
      alcohol. The data therefore delineate a pathway in which sporangia perceive cold
      temperatures through membrane rigidity, which activates signals that drive both
      zoosporogenesis and cold-box-mediated transcription.

PMID- 16607022
TI  - Cell division of Giardia intestinalis: flagellar developmental cycle involves
      transformation and exchange of flagella between mastigonts of a diplomonad cell.
AB  - Giardia intestinalis is a binucleated diplomonad possessing four pairs of
      flagella of distinct location and function. Its pathogenic potential depends on
      the integrity of a complex microtubular cytoskeleton that undergoes a profound
      but poorly understood reorganization during cell division. We examined the cell
      division of G. intestinalis with the aid of light and electron microscopy and
      immunofluorescence methods and present here new observations on the
      reorganization of the flagellar apparatus in the dividing Giardia. Our results
      demonstrated the presence of a flagellar maturation process during which the
      flagella migrate, assume different position, and transform to different flagellar
      types in progeny until their maturation is completed. For each newly assembled
      flagellum it takes three cell cycles to become mature. The mature flagellum of
      Giardia is the caudal one that possesses a privileged basal body at which the
      microtubules of the adhesive disk nucleate. In contrast to generally accepted
      assumption that each of the two diplomonad mastigonts develops separately, we
      found that they are developmentally linked, exchanging their cytoskeletal
      components at the early phase of mitosis. The presence of the flagellar
      maturation process in a metamonad protist Giardia suggests that the basal body or
      centriole maturation is a universal phenomenon that may represent one of the core
      processes in a eukaryotic cell.

PMID- 16607023
TI  - Specific effects of ribosome-tethered molecular chaperones on programmed -1
      ribosomal frameshifting.
AB  - The ribosome-associated molecular chaperone complexes RAC (Ssz1p/Zuo1p) and
      Ssb1p/Ssb2p expose a link between protein folding and translation. Disruption of
      the conserved nascent peptide-associated complex results in cell growth and
      translation fidelity defects. To better understand the consequences of deletion
      of either RAC or Ssb1p/2p, experiments relating to cell growth and programmed
      ribosomal frameshifting (PRF) were assayed. Genetic analyses revealed that
      deletion of Ssb1p/Ssb2p or of Ssz1p/Zuo1p resulted in specific inhibition of -1
      PRF and defects in Killer virus maintenance, while no effects were observed on +1
      PRF. These factors may provide a new set of targets to exploit against viruses
      that use -1 PRF. Quantitative measurements of growth profiles of isogenic wild
      type and mutant cells showed that translational inhibitors exacerbate underlying
      growth defects in these mutants. Previous studies have identified -1 PRF signals
      in yeast chromosomal genes and have demonstrated an inverse relationship between 
      1 PRF efficiency and mRNA stability. Analysis of published DNA microarray
      experiments reveals conditions under which Ssb1, Ssb2, Ssz1, and Zuo1 transcript
      levels are regulated independently of those of genes encoding ribosomal proteins.
      Thus, the findings presented here suggest that these trans-acting factors could
      be used by cells to posttranscriptionally regulate gene expression through -1
      PRF.

PMID- 16607024
TI  - The highly conserved family of Tetrahymena thermophila chromosome breakage
      elements contains an invariant 10-base-pair core.
AB  - As a typical ciliate, Tetrahymena thermophila is a unicellular eukaryote that
      exhibits nuclear dimorphism: each cell contains a diploid, germ line micronucleus
      (MICN) and a polyploid, somatic macronucleus (MACN). During conjugation, when a
      new MACN differentiates from a mitotic descendant of the diploid fertilization
      nucleus, the five MICN chromosomes are site-specifically fragmented into 250 to
      300 MACN chromosomes. The classic chromosome breakage sequence (CBS) is a 15-bp
      element (TAAACCAACCTCTTT) reported to be necessary and sufficient for chromosome
      breakage. To determine whether a CBS is present at every site of chromosome
      fragmentation and to assess the range of sequence variation tolerated, 31 CBSs
      were isolated without preconception as to the sequence of the chromosome breakage
      element. Additional CBS-related sequences were identified in the whole-genome
      sequence by their similarities to the classic CBS. Forty CBS elements behaved as
      authentic chromosome breakage sites. The CBS nucleotide sequence is more diverse
      than previously thought: nearly half of the CBS elements identified by unbiased
      methods have a variant of the classic CBS. Only an internal 10-bp core is
      completely conserved, but the entire 15-bp chromosome breakage sequence shows
      significant sequence conservation. Our results suggest that any one member of the
      CBS family provides a necessary and sufficient cis element for chromosome
      breakage. No chromosome breakage element totally unrelated to the classic CBS
      element was found; such elements, if they exist at all, must be rare.

PMID- 16607025
TI  - Giardia lamblia attachment force is insensitive to surface treatments.
AB  - Giardia lamblia cell populations show 90% detachment from glass under normal
      forces of 2.43+/-0.33 nN applied by centrifugation. Detachment forces were not
      significantly different for cells attached to positively charged, hydrophobic, or
      inert surfaces than for cells attached to plain glass. The insensitivity of
      attachment force to surface treatment is consistent with a suction-based
      mechanism of attachment.

PMID- 16607026
TI  - Cardiolipin in hydrogenosomes: evidence of symbiotic origin.
AB  - Hydrogenosomes are found in organisms that lack typical mitochondria. Cardiolipin
      is a phospholipid located exclusively in bacterial membranes and the inner
      membrane of mitochondria. Here we show, by cell fractionation, thin-layer
      chromatography, high-pressure liquid chromatography, and matrix-assisted laser
      desorption ionization-time of flight mass spectrometry that hydrogenosomes of
      Tritrichomonas foetus, a cattle vaginal parasite, contain cardiolipin, which is
      strong evidence for its endosymbiotic origin.

PMID- 16607027
TI  - Abiotic stress in rice. An "omic" approach.

PMID- 16607028
TI  - MEKHLA, a novel domain with similarity to PAS domains, is fused to plant
      homeodomain-leucine zipper III proteins.
AB  - Homeodomain (HD) proteins play important roles in the development of plants,
      fungi, and animals. Here we identify a novel domain, MEKHLA, in the C terminus of
      HD-Leu zipper (HD-ZIP) III plant HD proteins that shares similarity with a group
      of bacterial proteins and a protein from the green alga Chlamydomonas
      reinhardtii. The group of bacterial MEKHLA proteins is found in cyanobacteria and
      other bacteria often found associated with plants. Phylogenetic analysis suggests
      that a MEKHLA protein transferred, possibly from a cyanobacterium or an early
      chloroplast, into the nuclear genome of an early plant in a first step, and
      attached itself to the C terminus of an HD-ZIP IV homeobox gene in a second step.
      Further position-specific iterated-BLAST searches with the bacterial MEKHLA
      proteins revealed a subregion within the MEKHLA domain that shares significant
      similarity with the PAS domain. The PAS domain is a sensory module found in many
      proteins through all kingdoms of life. It is involved in light, oxygen, and redox
      potential sensation. The fact that HD-ZIP III proteins are transcription factors
      that have this sensory domain attached to their C terminus uncovers a potential
      new signaling pathway in plants.

PMID- 16607029
TI  - Integrating membrane transport with male gametophyte development and function
      through transcriptomics.
AB  - Male fertility depends on the proper development of the male gametophyte,
      successful pollen germination, tube growth, and delivery of the sperm cells to
      the ovule. Previous studies have shown that nutrients like boron, and ion
      gradients or currents of Ca2+, H+, and K+ are critical for pollen tube growth.
      However, the molecular identities of transporters mediating these fluxes are
      mostly unknown. As a first step to integrate transport with pollen development
      and function, a genome-wide analysis of transporter genes expressed in the male
      gametophyte at four developmental stages was conducted. Approximately 1,269 genes
      encoding classified transporters were collected from the Arabidopsis (Arabidopsis
      thaliana) genome. Of 757 transporter genes expressed in pollen, 16% or 124 genes,
      including AHA6, CNGC18, TIP1.3, and CHX08, are specifically or preferentially
      expressed relative to sporophytic tissues. Some genes are highly expressed in
      microspores and bicellular pollen (COPT3, STP2, OPT9), while others are activated
      only in tricellular or mature pollen (STP11, LHT7). Analyses of entire gene
      families showed that a subset of genes, including those expressed in sporophytic
      tissues, was developmentally regulated during pollen maturation. Early and late
      expression patterns revealed by transcriptome analysis are supported by
      promoter::beta-glucuronidase analyses of CHX genes and by other methods. Recent
      genetic studies based on a few transporters, including plasma membrane H+ pump
      AHA3, Ca2+ pump ACA9, and K+ channel SPIK, further support the expression
      patterns and the inferred functions revealed by our analyses. Thus, revealing the
      distinct expression patterns of specific transporters and unknown polytopic
      proteins during microgametogenesis provides new insights for strategic mutant
      analyses necessary to integrate the roles of transporters and potential receptors
      with male gametophyte development.

PMID- 16607032
TI  - Use of bacterial quorum-sensing components to regulate gene expression in plants.
AB  - We describe an efficient inducible system to regulate gene expression in plants
      based on quorum-sensing components found in Gram-negative bacteria such as
      Agrobacterium tumefaciens. These bacteria monitor their own population density by
      utilizing members of the N-acyl homoserine lactone family as inducers and a
      transcriptional activator as its receptor. In our study, we utilize the
      components from A. tumefaciens (i.e. 3-oxooctanyl-l-homoserine lactone [OOHL])
      synthesized by the TraI protein and its receptor, TraR. When OOHL binds to TraR,
      it recognizes its specific cis-element, the tra box. We translationally fused the
      eukaryotic VP16 activation domain to the N terminus of TraR. In the presence of
      OOHL, the chimeric VP16:TraR transcriptional regulator induces reporter gene
      expression in moss (Physcomitrella patens), barley (Hordeum vulgare), and carrot
      (Daucus carota) cells, as well as in transgenic Arabidopsis (Arabidopsis
      thaliana) seedlings. The inducible system shows a low level of reporter gene
      expression in the absence of the inducer. Foliar application and a floating-leaf
      assay in the presence of the inducer shows a 30- and 200-fold induction,
      respectively. Induction by foliar application of the inducer to whole seedlings
      is achieved within 8 h. The VP16:TraR activator also shows specificity for
      binding to its cognate inducer, OOHL. Based on microarray analyses, endogenous
      gene expression is not significantly affected due to overexpression of the TraR
      protein or presence of OOHL in either wild-type or lactone-inducible transgenic
      plants.

PMID- 16607034
TI  - Serum amyloid A generates high density lipoprotein with cellular lipid in an
      ABCA1- or ABCA7-dependent manner.
AB  - Serum amyloid A (SAA) is an amphiphilic helical protein that is found associated
      with plasma HDL in various pathological conditions, such as acute or chronic
      inflammation. Cellular lipid release and generation of HDL by this protein were
      investigated, in comparison with the reactions by apolipoprotein A-I (apoA-I) and
      several types of cells that appear with various specific profiles of cholesterol
      and phospholipid release. SAA mediated cellular lipid release from these cells
      with the same profile as apoA-I. Upregulation of cellular ABCA1 protein by liver
      X receptor/retinoid X receptor agonists resulted in an increase of cellular lipid
      release by apoA-I and SAA. SAA reacted with the HEK293-derived clones that stably
      express human ABCA1 (293/2c) or ABCA7 (293/6c) to generate cholesterol-containing
      HDL in a similar manner to apoA-I. Dibutyryl cyclic AMP and phorbol 12-myristate
      13-acetate, which differentiate apoA-I-mediated cellular lipid release between
      293/2c and 293/6c, also exhibited the same differential effects on the SAA
      mediated reactions. No evidence was found for the ABCA1/ABCA7-independent lipid
      release by SAA. Characterization of physicochemical properties of the HDL
      revealed that SAA-generated HDL particles had higher density, larger diameter,
      and slower electrophoretic mobility than those generated by apoA-I. These results
      demonstrate that SAA generates cholesterol-containing HDL directly with cellular
      lipid and that the reaction is mediated by ABCA1 and ABCA7.

PMID- 16607036
TI  - Comprehensive molecular phylogeny of the sub-family Dipterocarpoideae
      (Dipterocarpaceae) based on chloroplast DNA sequences.
AB  - Dipterocarpoideae, the largest sub-family of well-known plant family
      Dipterocarpaceae, dominates in South Asian rain forests. Although several
      previous studies addressed the phylogeny of the Dipterocarpaceae family,
      relationships among many of its genera from the Dipterocarpoideae sub-family are
      still not well understood. In particular, little is known about the relationships
      of the genera Vateriopsis, Stemonoporus, Vateria and inconsistence remains
      between phylogenetic results and taxonomic classifications of Shorea and Hopea
      species. We studied molecular phylogeny of the sub-family Dipterocarpoideae using
      the trnL-trnF spacer, trnL intron and the matK gene sequences of chloroplast DNA
      (cpDNA). This study is the first comprehensive phylogeny reconstruction for the
      sub-family Dipterocarpoideae based on cpDNA, as it includes most genera (14) and
      a large number of species (79) with most species endemic to Sri Lanka, as well as
      one species from Seychelles and one species from the genus Monotes from
      Madagascar. Phylogenetic trees were constructed using the Neighbor Joining (NJ)
      and Maximum Likelihood (ML) methods using combined set of sequences including all
      three cpDNA regions. The topologies of the NJ and ML trees were to a certain
      extent, consistent with the current taxonomy of Dipterocarpoideae based on
      morphology and with previous molecular phylogenies based on cpDNA. Furthermore,
      our results provided new evidence regarding the relationships of the following
      genera: Vateriopsis and Stemonoporus and about the validity of the previous
      morphology based classifications of Shorea species. In addition, the topology of
      our trees was consistent with the classification of Shorea species proposed by
      Maury (1978), Maury-Lechon (1979) and Symington (1943). Finally, our results
      provided evidence for the affinity of the genus Monotes to Asian
      Dipterocarpoideae rather than to Tiliaceae and indicated that it is a good
      candidate for outgroup species for future studies of the former sub-family.

PMID- 16607035
TI  - Interplay between lipoproteins and bee venom phospholipase A2 in relation to
      their anti-Plasmodium toxicity.
AB  - We previously showed that the in vitro intraerythrocytic development of the
      malarial agent Plasmodium falciparum is strongly inhibited by secreted
      phospholipases A(2) (sPLA(2)s) from animal venoms. Inhibition is dependent on
      enzymatic activity and requires the presence of serum lipoproteins in the
      parasite culture medium. To evaluate the potential involvement of host
      lipoproteins and sPLA(2)s in malaria, we investigated the interactions between
      bee venom phospholipase A(2) (bvPLA(2)), human triglyceride-rich lipoproteins,
      and infected erythrocytes. Even at high enzyme concentration (100x IC(50)),
      bvPLA(2) binding to Plasmodium-infected or normal erythrocytes was not detected.
      On the contrary, tight association with lipoproteins was observed through the
      formation of buoyant bvPLA(2)/lipoprotein complexes. Direct involvement of the
      hydrolysis lipid products in toxicity was demonstrated. Arachidonic acid (C20:4),
      linoleic acid (C18:2), and, to a lesser extent, docosahexaenoic acid (C22:6)
      appeared as the main actors in toxicity. Minimal oxidation of lipoproteins
      enhanced toxicity of the lipolyzed particles and induced their interaction with
      infected or normal erythrocytes. Fresh or oxidized lipolyzed lipoproteins induced
      the parasite degeneration without host cell membrane disruption, ruling out a
      possible membranolytic action of fatty acids or peroxidation products in the
      death process. In conclusion, our data enlighten on the capability of secreted
      PLA(2)s to exert cytotoxicity via the extracellular generation of toxic lipids,
      and raise the question of whether such mechanisms could be at play in
      pathophysiological situations such as malaria.

PMID- 16607030
TI  - Partial shotgun sequencing of the Boechera stricta genome reveals extensive
      microsynteny and promoter conservation with Arabidopsis.
AB  - Comparative genomics provides insight into the evolutionary dynamics that shape
      discrete sequences as well as whole genomes. To advance comparative genomics
      within the Brassicaceae, we have end sequenced 23,136 medium-sized insert clones
      from Boechera stricta, a wild relative of Arabidopsis (Arabidopsis thaliana). A
      significant proportion of these sequences, 18,797, are nonredundant and display
      highly significant similarity (BLASTn e-value < or = 10(-30)) to low copy number
      Arabidopsis genomic regions, including more than 9,000 annotated coding
      sequences. We have used this dataset to identify orthologous gene pairs in the
      two species and to perform a global comparison of DNA regions 5' to annotated
      coding regions. On average, the 500 nucleotides upstream to coding sequences
      display 71.4% identity between the two species. In a similar analysis, 61.4%
      identity was observed between 5' noncoding sequences of Brassica oleracea and
      Arabidopsis, indicating that regulatory regions are not as diverged among these
      lineages as previously anticipated. By mapping the B. stricta end sequences onto
      the Arabidopsis genome, we have identified nearly 2,000 conserved blocks of
      microsynteny (bracketing 26% of the Arabidopsis genome). A comparison of fully
      sequenced B. stricta inserts to their homologous Arabidopsis genomic regions
      indicates that indel polymorphisms >5 kb contribute substantially to the genome
      size difference observed between the two species. Further, we demonstrate that
      microsynteny inferred from end-sequence data can be applied to the rapid
      identification and cloning of genomic regions of interest from nonmodel species.
      These results suggest that among diploid relatives of Arabidopsis, small- to
      medium-scale shotgun sequencing approaches can provide rapid and cost-effective
      benefits to evolutionary and/or functional comparative genomic frameworks.

PMID- 16607037
TI  - WFL, a wheat FLORICAULA/LEAFY ortholog, is associated with spikelet formation as
      lateral branch of the inflorescence meristem.
AB  - FLORICAULA (FLO) of Antirrhinum and LEAFY (LFY) of Arabidopsis encode plant
      specific transcription factors, which are necessary and sufficient to specify
      floral meristem identity. We isolated WFL, a wheat FLO/LFY ortholog, and analyzed
      its expression pattern. RT-PCR analysis indicated that WFL is expressed
      predominantly in young spike. The WFL expression pattern during reproductive
      development was analyzed in more detail by using in situ hybridization technique.
      WFL transcripts were observed in all layers of the young spike excepting spikelet
      initiation sites as axillary meristem. In the double-ridge stage, WFL transcripts
      were localized in the lower ridge but were absent in the upper ridge, where
      spikelet meristem initiates. The WFL expression pattern indicated that WFL is
      associated with spikelet formation rather than floral meristem identity in wheat.
      As development of floret proceeds, the WFL transcripts were detectable in the
      developing palea, but not in other floral organs, suggesting that WFL may play a
      novel role in developing palea in the wheat floret.

PMID- 16607038
TI  - Complete nucleotide sequence of the A+T-rich region of Drosophila mauritiana
      mitochondrial DNA.
AB  - We determined the complete nucleotide sequence of the A+T-rich region of the maII
      type of mtDNA in D. mauritiana. The nucleotide sequence was found to contain
      3,206 bp. Three types of conserved element, i.e., type I element, type II
      element, and T-stretch, were included in this sequence, as reported for D.
      melanogaster. Comparison between the two species revealed that the type I
      elements were less conserved than the type II elements. However, each of these
      type I elements contained a G-stretch within a loop of a putative stem-loop
      forming sequence, which has also been observed in D. melanogaster. Moreover, in
      both type I and type II repeat arrays, the elements closest to the T-stretch
      diverged the most, due to nucleotide substitution and/or the insertion of short
      repeats. Sequence comparison of the two complete sequences of the A+T-rich region
      of D. melanogaster and the maII type of D. mauritiana, as well as comparison of
      partial sequences in other types of mtDNA within the melanogaster complex,
      suggested that the A+T-rich region in this complex has been maintained by
      concerted evolution after the duplication of two types of element, i.e., type I
      and type II.

PMID- 16607039
TI  - The mitochondrial genome of spotted green pufferfish Tetraodon nigroviridis
      (Teleostei: Tetraodontiformes) and divergence time estimation among model
      organisms in fishes.
AB  - We determined the whole mitochondrial genome sequence for spotted green
      pufferfish, Tetraodon nigroviridis (Teleostei: Tetraodontiformes). The genome
      (16,488 bp) contained 37 genes (two ribosomal RNA genes, 22 transfer RNA genes,
      and 13 protein-coding genes) plus control region as found in other vertebrates,
      with the gene order identical to that of typical vertebrates. The sequence was
      used to estimate phylogenetic relationships and divergence times among major
      lineages of fishes, including representative model organisms in fishes. We
      employed partitioned Bayesian approaches for these two analyses using two
      datasets that comprised concatenated amino acid sequences from 12 protein-coding
      genes (excluding the ND6 gene) and concatenated nucleotide sequences from the 12
      protein-coding genes (without 3rd codon positions), 22 transfer RNA genes, and
      two ribosomal RNA genes. The resultant trees from the two datasets were well
      resolved and largely congruent with those from previous studies, with spotted
      green pufferfish being placed in a reasonable phylogenetic position. The
      approximate divergence times between spotted green pufferfish and model organisms
      in fishes were 85 million years ago (MYA) vs. torafugu, 183 MYA vs. three-spined
      stickleback, 191 MYA vs. medaka, and 324 MYA vs. zebrafish, all of which were
      about twice as old as the divergence times estimated by their earliest
      occurrences in fossil records.

PMID- 16607031
TI  - A comparative genomics strategy for targeted discovery of single-nucleotide
      polymorphisms and conserved-noncoding sequences in orphan crops.
AB  - Completed genome sequences provide templates for the design of genome analysis
      tools in orphan species lacking sequence information. To demonstrate this
      principle, we designed 384 PCR primer pairs to conserved exonic regions flanking
      introns, using Sorghum/Pennisetum expressed sequence tag alignments to the Oryza
      genome. Conserved-intron scanning primers (CISPs) amplified single-copy loci at
      37% to 80% success rates in taxa that sample much of the approximately 50-million
      years of Poaceae divergence. While the conserved nature of exons fostered cross
      taxon amplification, the lesser evolutionary constraints on introns enhanced
      single-nucleotide polymorphism detection. For example, in eight rice (Oryza
      sativa) genotypes, polymorphism averaged 12.1 per kb in introns but only 3.6 per
      kb in exons. Curiously, among 124 CISPs evaluated across Oryza, Sorghum,
      Pennisetum, Cynodon, Eragrostis, Zea, Triticum, and Hordeum, 23 (18.5%) seemed to
      be subject to rigid intron size constraints that were independent of per
      nucleotide DNA sequence variation. Furthermore, we identified 487 conserved
      noncoding sequence motifs in 129 CISP loci. A large CISP set (6,062 primer pairs,
      amplifying introns from 1,676 genes) designed using an automated pipeline showed
      generally higher abundance in recombinogenic than in nonrecombinogenic regions of
      the rice genome, thus providing relatively even distribution along genetic maps.
      CISPs are an effective means to explore poorly characterized genomes for both DNA
      polymorphism and noncoding sequence conservation on a genome-wide or candidate
      gene basis, and also provide anchor points for comparative genomics across a
      diverse range of species.

PMID- 16607040
TI  - RECS1 deficiency in mice induces susceptibility to cystic medial degeneration.
AB  - RECS1 is a novel shear stress-responsive gene that encodes a protein putatively
      forming seven-span transmembrane domains. We reports here that mouse RECS1
      (mRECS1) transcripts is detected in most tissues except for thymus, spleen and
      testis. The putative cytoplasmic N-terminus of mRECS1 has a high content of
      proline (23%) and glycine (12%) residues, contains one PPXY motif, multiple PXXP
      motifs and one overlapping P(T/S)AP and PPXY motif (P(T/S)APPXY). The PPXY motif
      lies within one potential PEST sequence (PEST score: +7.65). We prepared anti
      RECS1 polyclonal antibody and found by western blot analysis that the mRECS1
      protein in the lung and aorta was detected as a 34.4 kDa band. However, one
      shifted 58 kDa band or three shifted bands (48, 69, 82 kDa) were detected in the
      heart or the liver, respectively. Since northern blot detected only one species
      of mRECS1 mRNA in heart and liver tissues, as well as other tissues
      (approximately 2.2 kb), these differences in molecular weight seem to be due to
      posttranslational modification. Biochemical fractionation and RECS1-GFP fusion
      protein revealed that RECS1 localizes at the endosomal/lysosomal membranes in the
      cytoplasm. To understand the function of RECS1 in the body, we made RECS1
      knockout (KO) mice and found that RECS1 KO mice (older than 14 months) are prone
      to cystic medial degeneration (CMD). Taken together, we conclude that RECS1 is an
      endosomal/lysosomal membrane protein which plays protective roles in vascular
      remodeling.

PMID- 16607041
TI  - DjlA negatively regulates the Rcs signal transduction system in Escherichia coli.
AB  - The Rcs signal transduction system of Escherichia coli regulating capsular
      polysaccharide synthesis (cps) genes is activated by overexpression of the djlA
      gene encoding a cytoplasmic membrane-anchored DnaJ-like protein. However, by
      monitoring the expression of a cpsB'-lac fusion in pgsA- and mdoH-null mutants in
      which the Rcs system is activated, we found that the Rcs activity was further
      increased by deletion of djlA and decreased by low-level extrachromosomal
      expression of djlA. Furthermore, deletion of djlA in a wild-type strain led to
      small but significant increase of the basal-level activity of the Rcs system.
      These results demonstrate that DjlA functions as a negative regulator of the Rcs
      system unless abnormally overproduced.

PMID- 16607042
TI  - Anther-specific genes, which expressed through microsporogenesis, are temporally
      and spatially regulated in model legume, Lotus japonicus.
AB  - Pollen germination and pollen tube elongation are important for pollination and
      fertilization in higher plants. To date, several pollen-specific genes have been
      isolated and characterized. However, there is little information about the
      precise spatial and temporal expression pattern of pollen-specific genes in
      higher plants. In our previous study, we identified 132 anther-specific genes in
      the model legume Lotus japonicus by using cDNA microarray analysis, though their
      precise expression sites in the anther tissues were not determined. In this
      study, by using in situ hybridization experiments, we determined the spatial and
      temporal expression sites of 46 anther-specific genes (ca. 35%), which were
      derived from two groups, cluster I-a and cluster II-a, according to flower
      developmental stages. In the case of the genes grouped into cluster I-a, thirteen
      clones were characterized. The specific hybridized signals were varied among the
      clones, and were observed in tapetum cells, microspores, and anther walls at the
      early developmental stage of anther tissues. In the case of the genes classified
      into cluster II-a, we used thirty three different cDNA clones encoding primary
      and secondary metabolism-related proteins, cell wall reconstruction-related
      proteins, actin reorganization-related proteins, and sugar transport-related
      proteins, etc., as a probe. Interestingly, all genes in these thirty three clones
      examined were specifically expressed in the bicellular pollen grains, though the
      signal intensity was varied among clones. From the data of the cluster II-a
      genes, the mRNAs related to pollen germination and pollen tube elongation were
      specifically transcribed and preserved in mature pollen grains.

PMID- 16607043
TI  - Comparative analysis of the S-intergenic region in class-II S haplotypes of self
      incompatible Brassica rapa (syn. campestris).
AB  - In the Brassica self-incompatibility (SI) system, a pollen determinant, SP11, is
      involved in dominance/recessive relationships in pollen SI phenotypes. In order
      to gain some insights into the genomic structure around the SP11 and the
      mechanisms that give dominance/recessive relationships, we characterized the
      genomic region containing SP11 and SRK genes in three pollen recessive class-II S
      haplotypes. The direction of transcription of S genes was completely conserved
      among class-II S haplotypes. However, the region between SP11 and SRK (S
      intergenic region) was highly polymorphic without short repetitive sequences. In
      addition, we found a sequence similarity between the short repetitive sequence
      and 5'-upstream region of SP11. This sequence similarity was found to be
      potentially related to the expression of dominance relationships through the
      change of chromatin structure.

PMID- 16607044
TI  - Poststenting axial redistribution of atherosclerotic plaque into the reference
      segments and lumen reduction at the stent edge: a volumetric intravascular
      ultrasound study.
AB  - Lumen enlargement during coronary stenting results from vessel expansion and
      axial redistribution of atheromatous plaque along the stented segment and
      proximal and distal reference segments. Plaque burden predicts stenosis at the
      stent edge. The aim of this study was to investigate the fate of shifted plaque
      with special reference to whether or not plaque shift (PSh) correlates with late
      lumen reduction. This is a prospective study conducted on 54 consecutive patients
      who underwent bare metal stenting. In all stent edges (108 edges), PSh volume was
      measured as postintervention plaque-media volume (PMV) minus preintervention PMV.
      Changes in lumen volume (DeltaLV), vessel volume (DeltaVV), and PMV (DeltaPMV)
      were measured by serial intravascular ultrasound (IVUS) examination. After
      stenting, PSh was detected in 81.5% of proximal edges versus 72.2% of distal
      edges (P = 0.36). It correlated significantly with DeltaVV (r = 0.34, P = 0.002),
      and inversely with DeltaLV (r = 0.32, P = 0.003). However, at 6-month follow-up,
      it did not correlate with DeltaLV (r = -0.03, P = 0.8), DeltaVV (r = 0.1, P =
      0.6), or DeltaPMV (r = 0.1, P = 0.4). Furthermore, DeltaLV correlated more
      strongly with DeltaVV (r = 0.62, P < 0.00001) than with DeltaPMV (r = -0.39, P =
      0.001). By multivariate analysis, PSh area was an independent predictor of the
      postintervention change in lumen area (partial eta squared 0.21, P = 0.01), but
      not the follow-up change. Two patients (3.7%) developed proximal edge stenosis
      with no evident PSh after stenting. Thus, axial redistribution of atheromatous
      plaque into the reference segments was frequently encountered after stenting.
      Although PSh correlated with the immediate reduction in stent edge lumen volume,
      it did not correlate with the late lumen reduction.

PMID- 16607045
TI  - Effects of angiotensin-converting enzyme inhibitors or an angiotensin receptor
      blocker in combination with aspirin and cilostazol on in-stent restenosis.
AB  - It remains to be determined whether adding an angiotensin-converting enzyme
      inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) to antiplatelet
      therapy has a therapeutic benefit on in-stent restenosis. After successful
      coronary stenting, 165 patients (167 lesions) were randomly assigned to a basal
      (aspirin 162 mg + cilostazol 200 mg/day), ACEI (basal treatment + quinapril 10 mg
      or perindopril 4 mg/day), or ARB (basal treatment + losartan 50 mg/day) treatment
      group. Quantitative coronary angiography was performed before, immediately
      following, and 6 months after stenting. Follow-up coronary angiography was
      completed in 126 patients (128 lesions). Restenosis rates tended to be higher
      (12, 26, and 12% for the basal, ACEI, and ARB groups, respectively), and target
      lesion revascularization rates were higher in the ACEI group than in the other
      groups (9, 23,* and 5%, respectively, *P < 0.05 versus basal group). Moreover,
      late lumen loss was higher in the ACEI group than in the basal group (0.60 +/-
      0.55, 0.98 +/- 0.61* and 0.73 +/- 0.64 mm in the basal, ACEI, and ARB groups,
      respectively). The combinations of an ACEI or ARB with aspirin and cilostazol are
      ineffective for the prevention of in-stent restenosis, and an ACEI may even
      promote intimal proliferation after stent implantation.

PMID- 16607046
TI  - Is single or double aortic clamping safer in terms of cerebral outcome during
      coronary bypass surgery?
AB  - The purpose of the present study was to investigate retrospectively which aortic
      clamping technique, the single clamp technique (SCT) or double clamping technique
      (DCT), is safer in terms of cerebral functions in patients who have undergone
      coronary bypass surgery. We evaluated 1100 patients who underwent coronary artery
      bypass graft surgery at our institute from 1998 to 2004. The two groups, SCT (n =
      550, 50%) and DCT (n = 550, 50%), were comparable with respect to smoking,
      hypertension, hypercholesterolemia, diabetes mellitus, chronic obstructive
      pulmonary disease, peripheral arterial disease, history of neurological events,
      creatinine levels, and existence of a carotid lesion. No significant differences
      between the SCT and DCT groups were observed in terms of cardiac and cerebral
      complications perioperatively and postoperatively. Both single and double
      clamping techniques have advantages and disadvantages in patients undergoing
      coronary bypass surgery.

PMID- 16607047
TI  - Relationship between the mismatch of 123I-BMIPP and 201Tl myocardial single
      photon emission computed tomography and autonomic nervous system activity in
      patients with acute myocardial infarction.
AB  - The purpose of this study was to elucidate the relationship between the mismatch
      of thallium-201(Tl) and iodine-123-beta-methyl-iodophenyl-pentadecanoic acid
      (BMIPP) myocardial single-photon emission computed tomography (SPECT) and
      autonomic nervous system activity in myocardial infarction (MI) patients. The
      subjects were 40 patients (34 males, 6 females) who underwent examinations by
      123I-BMIPP and 201Tl myocardial SPECT imaging and 24-hour Holter monitoring
      within a 3-day period 3 weeks after the onset of their first MI. R-R intervals
      were analyzed every hour over a period of 24 hours by fast Fourier transformation
      (FFT). High frequency (HF) and low frequency (LF) were defined as markers of
      cardiac vagal activity in the former and the LF/HF ratio as sympathetic activity.
      Greater or more extensive decreases in the BMIPP image than that in the Tl image
      were defined as a positive mismatch. Patients were divided into positive and
      negative mismatch groups of 20 patients each. There were no significant
      differences between the 2 groups in age, sex, site of infarction, max CK
      (creatine kinase), max CK-MB, or left ventricular ejection fraction. The
      incidences of clinical signs suggesting residual myocardial ischemia were
      significantly greater in the positive than in the negative mismatch group (P <
      0.05). The mean values for HF over the entire 24-hour period and over the 5-hour
      nocturnal period (0-5 AM) in the positive mismatch group were both significantly
      lower than those in the negative mismatch group (P < 0.001 in both groups). The
      24-hour mean HF and mean nighttime HF in patients with signs of residual ischemia
      were both significantly lower than in those without signs of residual ischemia in
      the positive mismatch group (P < 0.05 in both groups). The mean LF/HF ratio for
      both the entire 24-hour and the nocturnal period in the positive mismatch group
      were significantly higher than those in the negative mismatch group (P < 0.001, P
      < 0.05, respectively). The daily profile of hourly HF measurements was
      significantly lower in the positive mismatch group than in the negative mismatch
      group (P < 0.02). The mean values of HF for 24-hour and 5-hour periods were
      significantly lower in patients with signs of residual ischemia in the positive
      mismatch group than in those with signs of residual ischemia in the negative
      mismatch group (P < 0.01, P < 0.02, respectively). There were no significant
      differences between the patients with signs of residual ischemia in the negative
      mismatch group and those without signs of residual ischemia in the positive and
      negative mismatch group with regard to the mean values of HF and the LF/HF ratio
      measured every hour for 24 hours and 5 hours. It is concluded from the present
      study that the findings of a mismatch on 123I-BMIPP and 201Tl myocardial SPECT 3
      weeks after a first acute myocardial infarction with uncomplicated moderate or
      severe heart failure and decreased heart rate variability are related to residual
      myocardial ischemia. A combined assessment of heart rate variability in 24-hour
      Holter ECG monitoring and perfusion-metabolism mismatch in 123I-BMIPP and 201Tl
      myocardial SPECT is useful for determining residual myocardial ischemia in the
      follow-up of those with acute myocardial infarction.

PMID- 16607048
TI  - Age differences in the delivery of cardiac management to women versus men with
      acute myocardial infarction: an evaluation of the TAMIS-II data.
AB  - It is of concern that women are more likely to undergo fewer diagnostic tests and
      receive less treatment for acute myocardial infarction (AMI) than men. Our
      retrospective Tokai Acute Myocardial Infarction Study (TAMIS) indicated that
      there were gender differences according to age groups; however, the exact nature
      of these gender differences remains unclear. Therefore, using data from TAMIS-II,
      we studied the influence of gender on the delivery of cardiac management
      according to 2 age groups (< 65, >or= 65). TAMIS-II is a prospective study of all
      consecutive patients admitted to the 15 acute care hospitals in the Tokai region
      with the diagnosis of AMI from 2001 to 2003. A total of 169 younger women, 1246
      younger men, 616 older women, and 1240 older men were included. Data on patient
      demographics, in-hospital course, comorbid conditions, electrocardiography (ECG),
      ultrasound-echocardiogram (UCG), treadmill test (TMT), coronary angiography
      (CAG), percutaneous coronary intervention (PCI), coronary artery bypass grafts
      (CABG), intra-aortic balloon pump (IABP), mechanical ventilation, and in-hospital
      or discharge medications (thrombolytics, vasopressors, aspirin, beta-blockers,
      angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, nitrates)
      were collected. After controlling for these baseline variables, only lipid
      lowering therapy tended to be more frequent in women than in men among the
      elderly (OR 1.55, 95%CI 1.00-2.38). The results from this Japanese chart review
      study, derived from detailed clinical data, indicated that the delivery pattern
      of cardiac management for female and male AMI patients during hospitalization and
      at discharge was very similar among the younger and older populations.

PMID- 16607049
TI  - Can segmental pulmonary vein ablation reduce the recurrence of atrial
      fibrillation when using a higher RF power, larger tip electrode catheter, and
      additional RF deliveries?: the limitations of point-by-point RF ablation.
AB  - The aim of this study was to investigate whether segmental ostial catheter
      ablation (SOCA) designed to prevent the electrical connections (ECs) between the
      left atrium and pulmonary veins (PVs) might help increase the efficacy of SOCA in
      paroxysmal atrial fibrillation (PAF). PV mapping and successful SOCA were
      performed with a basket catheter in 108 consecutive patients with PAF.
      Radiofrequency energy was delivered using a maximum output of 30 W with a 4 mm
      tip catheter (group I; 47) or 40 W with an 8 mm tip catheter (group II; 61). Only
      in the group II patients were additional radiofrequency deliveries to the
      specific sites where the ECs tended to recover performed after successful SOCA.
      After the first procedure, PAF recurred in 47% of the group I patients and 32% of
      the group II patients. In all 27 patients who underwent repeat procedures, EC
      recoveries were observed more frequently in group I than in group II (69% versus
      49%; P < 0.05). After multiple procedures, there was more freedom from PAF in
      group II (84%) than in group I (66%) (P < 0.05). SOCA with a higher RF power,
      larger tip catheter, and additional RF deliveries could achieve a more effective
      SOCA.

PMID- 16607050
TI  - Predictive impact of the inducibility of ventricular fibrillation in patients
      with Brugada-type ECG.
AB  - The natural history of asymptomatic individuals with a Brugada-type
      electrocardiogram (ECG) is still controversial. In this study, we evaluated
      ventricular fibrillation (VF) inducibility in Brugada-type ECG patients and
      compared it with other risk factors to clarify the significance of these data on
      their prognosis. The study population consisted of 38 patients who presented with
      a typical ST-segment elevation in the precordial leads and underwent an
      electrophysiological study (EPS). The patients were divided into 3 groups; group
      A: patients with spontaneous ventricular fibrillation (VF) (n = 5), group B:
      patients without clinical VF but with inducible VF in EPS (n = 16), and group C:
      patients with neither clinical nor inducible VF (n = 17). The clinical features,
      diagnostic results, and prognosis were compared among these groups. During the
      follow-up period of 26 +/- 19 months, 2/5 (group A), 1/16 (group B), and 0/17
      (group C) patients suffered fatal arrhythmic events. None of the clinical
      features showed any significant difference, although the incidence of positive
      results in a drug challenge test was higher in groups A and B than in group C (P
      < 0.05). On the other hand, VF inducibility was higher in patients with positive
      results in the drug challenge test than in patients with negative results (59%
      versus 13%; P < 0.05). No VF episodes were observed in patients without VF
      induction, although one was observed in 1 of 16 patients with VF induction in
      asymptomatic Brugada syndrome. The drug challenge test appears to be useful for
      predicting VF inducibility even though it is a noninvasive test.

PMID- 16607051
TI  - Multivariate analysis for operative mortality in obstructive prosthetic valve
      dysfunction due to pannus and thrombus formation.
AB  - The objective of the present study was to investigate the risk factors for early
      hospital mortality in reoperations performed for obstructive prosthetic valve
      dysfunction. Between January 1994 and April 2005, 63 patients underwent
      reoperation for obstructive prosthetic valve dysfunction. The mean age of the
      patients was 40.3 +/- 12.8 years. The mitral valve was replaced in 47 (74.6%)
      patients, the aortic valve in 6 (9.5%) patients, and both valves in 10 (15.9%)
      patients. Forty-three (68.2%) patients underwent emergency reoperations. Early
      hospital mortality occurred in 13 (20.6%) patients. The ethiology of the valve
      dysfunction was pannus formation in 45 (71.4%) patients and thrombus formation in
      18 (28.6%). Pannus and thrombus were localized at the atrial side of the
      prosthetic valve in 15 (23.9%) patients, at the ventricular side in 13 (20.6%),
      and at both sides in 35 (55.5%). Inadequate anticoagulation was diagnosed in 28
      of 63 (44.4%) patients. The mean INR level in these 28 patients was 1.43 +/-
      0.24. In multivariate analysis, the only risk factor for early hospital mortality
      was left ventricular ejection fraction (P = 0.015; Odds: 0.000, 95% CI: 0.000
      0.043). It is concluded reoperations for prosthetic valve dysfunction have a high
      mortality rate. This study revealed that left ventricular dysfunction is the
      major determinant of surgical mortality in patients requiring reoperation for
      valve dysfunction due to pannus or thrombus.

PMID- 16607052
TI  - Focalized contractile impairment at hypertrophied myocardium proven in
      consideration of wall stress in patients with hypertrophic cardiomyopathy.
AB  - In hypertrophic cardiomyopathy (HCM) a hyperkinetic state is sometimes observed
      in spite of impaired systolic function in the hypertrophied myocardium. The aim
      of the present study was to determine the mechanism of this paradox. Seventeen
      patients with HCM and 10 normal subjects underwent cine magnetic resonance (MR)
      imaging to measure percent systolic wall thickening and percent fractional
      shortening. The ratio of systolic radial wall stress of the LV at the
      hypertrophied myocardium over that at the nonhypertrophied myocardium was
      evaluated to describe the focal advantageous condition for wall thickening. The
      ratio was 0.66 +/- 0.36 at the start of contraction and 0.78 +/- 0.31 at early
      systole, indicating consistently smaller radial wall stress at the hypertrophied
      myocardium. Although the condition for contraction was favorable (a ratio less
      than 1.00), percent systolic wall thickening at the hypertrophied myocardium
      (23.0 +/- 11.8%) was smaller than that at the nonhypertrophied myocardium (70.5
      +/- 32.3%). Smaller end-diastolic dimension (HCM group; 45.2 +/- 4.2 mm,
      reference group; 48.9 +/- 4.1 mm, P = 0.04) with a statistically identical value
      of systolic decrease in intraventricular dimension (HCM group; 19.7 +/- 3.9 mm,
      reference group; 18.9 +/- 3.2 mm, P = 0.60) yielded high percent fractional
      shortening in patients with HCM (43.5 +/- 7.6%). Although contractile impairment
      was proven at the hypertrophied region with low radial wall stress in the HCM
      group, the smaller end-diastolic dimension in this group resulted in high percent
      fractional shortening.

PMID- 16607053
TI  - A simplified clinical model to predict pulmonary embolism in patients with acute
      dyspnea.
AB  - The objective of the present study was to develop a simple clinical model for
      predicting pulmonary embolism (PE) in patients with acute dyspnea in the
      emergency room. PATIENTS AND MEASUREMENTS: We enrolled 56 patients diagnosed with
      PE, and 92 consecutive patients without PE, all of whom presented with acute
      dyspnea in the emergency room. Primary emergency-room physicians assessed the
      initial evaluation and interpretation of various laboratory findings. Some
      significantly independent predictors of PE were identified and integrated into a
      clinical model of pretest probability: low (< 30%), intermediate (>or= 30%, <or=
      70%), and high (> 70%). After setting up the model, another 40 patients (16 with
      PE, 24 without PE) were tested using the pretest model. Clinical variables
      associated with an increased likelihood of PE were being female and having
      unilateral low-leg edema, a high alveolar-arterial oxygen gradient, a clear chest
      x-ray, and electrocardiographic findings of right ventricular strain. Variables
      associated with a decreased likelihood of PE were cough, chest tightness, and
      unclear breath sounds. Our clinical model predicted that 95% of patients with PE
      had a high or low probability of PE. The positive predictive value for high
      probability was 94.1% and the negative predictive value for low probability was
      94.4%. In the tested group, the positive predictive value for high probability
      was 92.9%. The negative predictive value for low probability was 91.3%. This
      simple and easily available prediction model was useful for estimating the
      pretest probability of PE in patients with acute dyspnea.

PMID- 16607054
TI  - Analysis of factors affecting willingness to pay for cardiovascular disease
      related medical services.
AB  - Recently, application of the contingent valuation method (CVM) to health care is
      increasing to measure the willingness to pay (WTP) for specific medical services.
      In this study, we measured WTP for the outpatient treatment of hypertension and
      inpatient treatment of myocardial infarction (MI) in Japan's healthcare system,
      using CVM via an Internet questionnaire survey in 547 citizens aged 40 to 49
      years. WTP was measured with the payment cards method from an ex post consumer
      based perspective. The payment vehicle was out-of-pocket copayment under public
      medical insurance. The participants were asked their preferences with respect to
      medical institutions, and 3 comprehensive characteristics were extracted from the
      requested information by principal component analysis. Categorical regression was
      performed to analyze the factors affecting WTP. The mean WTP for hypertension
      treatment was 75.03 dollars/month, and that for the treatment of MI was 8,928.70
      dollars (1 dollar = 105 Japanese yen). WTP for hypertension treatment was
      significantly high in married males and the group without symptoms, but was not
      associated with income. WTP for the treatment of MI was significantly high in the
      high-income group, married males, and the group with symptoms. Among the 3
      principle components, "objective evaluation" was significantly associated with
      WTP for the treatment of MI. As for serious diseases such as MI, the income
      associated differences in WTP suggest the necessity for reinforcement of the
      safety net for the low-income group. Although asymptomatic, hypertension requires
      continuous treatment. For such diseases, uniformly low copayment should be
      established irrespective of annual income.

PMID- 16607055
TI  - Different effects of propranolol, phenylephrine, and saline volume loading on
      catecholamine-induced left ventricular outflow tract obstruction in acute
      coronary syndrome.
AB  - Hemodynamic deterioration due to left ventricular outflow tract (LVOT)
      obstruction can occur during catecholamine infusion in patients with acute
      coronary syndrome (ACS). The purpose of the present study was to compare the
      utility of propranolol, phenylephrine infusion, and rapid saline loading for
      reversal of dobutamine-induced LVOT obstruction in a canine model of ACS. ACS was
      induced via left anterior descending artery ligation in 21 open-chest
      anesthetized dogs, and LVOT obstruction, defined as an LVOT gradient > 30 mmHg,
      was induced by dobutamine infusion (20 to 40 microg/kg/min). Subsequently, the
      effects of propranolol infusion (0.7 to 1.0 microg/kg/min, n = 8), phenylephrine
      infusion (10 to 200 microg/kg/min, n = 7), and saline loading (200 to 400 mL/hr,
      n = 6) were assessed by serial hemodynamic measurements. All interventions
      produced significant and comparable improvements in the LVOT pressure gradient
      (propranolol: 60 +/- 16 to 15 +/- 12; phenylephrine: 68 +/- 15 to 12 +/- 10;
      saline loading: 58 +/- 18 to 22 +/- 10 mmHg; P < 0.001 for baseline versus
      postintervention; P = NS for comparison between interventions). Phenylephrine
      produced the greatest elevation in aortic pressure (propranolol: +15 +/- 13;
      phenylephrine: +51 +/- 36; saline loading: +15 +/- 15 mmHg; P < 0.05), while
      saline loading produced the greatest increase in cardiac output (propranolol:
      +0.05 +/- 0.12; phenylephrine: +0.28 +/- 0.37; saline loading: +0.73 +/- 0.48
      L/min; P < 0.05). Propranolol was the only intervention that produced a
      significant decrease in diastolic pulmonary artery pressure (16 +/- 5 to 11 +/- 3
      mmHg, P < 0.05). Propranolol, phenylephrine infusion, and saline volume loading
      were similarly effective in reversing dobutamine-induced LVOT obstruction in this
      canine model of ACS. However, each intervention produced different hemodynamic
      effects with potentially different clinical indications.

PMID- 16607056
TI  - Specificity of vascular reactivity and remodeling after repeated endothelial
      injury in a swine model.
AB  - We investigated the difference in vascular responses and remodeling between
      coronary and iliac arteries after repeated endothelial denudation. Endothelial
      denudation of the left anterior descending coronary artery (LAD) and the right
      common iliac artery (RIA) was repeated 4 times twice a month using a Fogarty
      catheter in 21 pigs. Vascular responses to vasoactive drugs were evaluated as %
      luminal diameter changes on contrast angiography 2 weeks after the last
      denudation. Corresponding nondenuded sites, ie, the left circumflex coronary
      artery (LCX) and the left common iliac artery (LIA), were used as references.
      Acetylcholine (1 microg/kg) did not constrict the LCX (0 +/- 1%) and the LAD (1
      +/- 1%, P < 0.05), whereas it constricted the RIA (20 +/- 6%) but not the LIA (-3
      +/- 3%, P < 0.01). Alternatively, serotonin (10 microg/kg) constricted the LAD
      strikingly (88 +/- 5%, P < 0.01 versus LCX and RIA), as well as the RIA (35 +/-
      10%, P < 0.05 versus LIA). Vasodilator responses to substance P and isosorbide
      dinitrate were not different after injury in both arteries. The intima-to-media
      ratio and adventitia-to-media ratio of the relevant site in cross section of
      tissue sample from LAD were greater than those from LCX, and were more prominent
      than those from RIA. The results show that vascular tone regulation after the
      endothelial injury and vascular remodeling might be altered in a vessel-specific
      manner.

PMID- 16607057
TI  - Usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography in a
      patient with Takayasu's arteritis associated with antiphospholipid syndrome.
AB  - A 36-year-old woman was admitted for recurring chest pain and hemoptysis. Blood
      pressure in the right and left arms was equal, and no murmurs or bruits were
      heard. Body temperature was normal on admission and remained within the normal
      range during the hospital stay. C-reactive protein was slightly elevated (2.3
      mg/dL) and lupus anticoagulant was positive. Angiography showed no abnormality of
      the aorta or its branches, but the left pulmonary artery showed occlusion at the
      proximal portion. Computed tomography (CT) revealed segmental wall thickening of
      the thoracic aorta. Fluorine-18-fluorodeoxyglucose positron emission tomography
      (18FDG PET) showed high uptake in the proximal portion of the left pulmonary
      artery and in the thoracic aorta with wall thickening on CT. Based on these
      findings, a diagnosis of Takayasu's arteritis associated with antiphospholipid
      syndrome was made and high-dose steroid therapy (prednisolone 30 mg/day) was
      started. Two months later, the C-reactive protein level had decreased from 2.3
      mg/dL to 1.1 mg/dL, and both the focal wall thickening and (18)FDG uptake of the
      thoracic aorta were decreased. 18FDG PET was useful for evaluating the efficacy
      of the steroid therapy in addition to making a diagnosis of Takayasu's arteritis
      associated with antiphospholipid syndrome.

PMID- 16607058
TI  - Beraprost sodium-induced hypotension in two patients after cardiac surgery.
AB  - Two episodes of hypotension caused by oral beraprost sodium administration
      following cardiac surgery are described. The first case was a 67-year-old female
      who underwent concomitant surgery for mitral valve replacement, tricuspid
      annuloplasty, and a radiofrequency maze procedure for atrial fibrillation. The
      second case was a 45-year-old female who underwent 4-vessel coronary artery
      bypass grafting associated with endarterectomy in the right coronary artery.
      Beraprost sodium was administered for the treatment of residual pulmonary
      hypertension in the first case, and was initiated as an antiplatelet agent
      following coronary endarterectomy in the second case. Hypotension occurred at
      approximately one hour after beraprost sodium administration in both cases.
      Careful observation to prevent this adverse effect is critical after the
      administration of beraprost sodium, especially in patients who have undergone
      cardiac surgery.

PMID- 16607059
TI  - New method of tracing blood hemoglobin concentration to hematocrit ratio for
      monitoring plasma dilution and osmotic origin shifts in blood.
AB  - Blood hemoglobin concentration and hematocrit are probably the most widely used
      parameters for outpatient and inpatient examination. In addition to their
      inherent significance for evaluation of blood viscosity and oxygen carrying
      capacity, these parameters are traditionally used as tracers of plasma dilution.
      Blood test derived results are conventionally recorded on multiple pages in
      patient's medical records making dynamical investigations tedious and time
      consuming. In addition, research results describing plasma dilution by means of
      hemoglobin or hematocrit are presented in a clinically unpractical way. A new
      method, referred to as HBS Graphics (patent pending--USA serial # 60/712809) is
      introduced for the first time in this article. This method of evaluation of
      dynamical hemoglobin concentration, hematocrit and mean corpuscular hemoglobin
      concentration value deploys interfering parameter shifts for the evaluation of
      plasma dilution in relation to osmotic dynamics. The HBS Graphics complements two
      coordinate systems--hemoglobin concentration and hematocrit--with incorporated
      mean corpuscular hemoglobin concentration value specific trends referred to as
      radiating lines. Isosmotic plasma dilution and erythrocyte volume shifts follow
      radiating lines, while osmotic shifts induce intertrend shifts. This article also
      reviews other methods of tracing plasma dilution by means of blood hemoglobin
      concentration and hematocrit dynamics.

PMID- 16607060
TI  - Changes in quality of life after esophageal resections for carcinoma.
AB  - OBJECTIVE: To evaluate the changes of the quality of life after the surgery for
      esophageal carcinoma and to find out whether these changes are influenced by the
      extent of the resection and lymphadenectomy. PATIENTS AND METHODS: A total of 49
      patients in whom esophageal carcinoma had been resected with curative intent and
      who stayed disease-free for at least twelve months after the surgery were
      studied. Twenty-four patients (48.9%) underwent two-field lymphadenectomy and
      intrathoracic esophagogastric anastomosis (group T), while in another twenty-five
      patients three-field lymphadenectomy and cervical esophagogastric anastomosis
      were performed (group C). To determine the impact of surgery quality of life was
      assessed in each patient just before the surgery, on the day of the discharge and
      at three-month intervals until the end of the first postoperative year. The
      quality of life was measured by means of European Organization for Research and
      Treatment of Cancer Quality of Life Questionnaire Version 3.0. RESULTS: Compared
      with the preoperative assessment quality of life had decreased at discharge but
      was restored within 3-12 months. The emotional functioning had increased just
      after the surgery. Significant differences between groups C and T were found in
      global health, physical, and role functioning scales. CONCLUSIONS: Majority of
      the aspects of quality of life deteriorated after the radical surgery for
      esophageal carcinoma and regained the preoperative level before the end of the
      first postoperative year. Major surgical procedure (three-field lymphadenectomy
      and cervical esophagogastric anastomosis) gives some disadvantages in physical,
      social and role functioning during the first six postoperative months.

PMID- 16607061
TI  - Clinical effectiveness of dentin sealer in treating dental root sensitivity
      following periodontal surgery.
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of a
      commercially available light-cured, resin-based dentin sealer in the treatment of
      postoperative sensitivity of roots with gingival recession of different extent.
      MATERIALS AND METHODS: The study was a case control, randomized, blind design. A
      total of 62 patients with the presence of chronic periodontitis, who required
      periodontal surgery, participated in this study. All recipients underwent flap
      operation. After the periodontal surgery 641 teeth were selected for the study.
      The pain intensity was determined by using visual analogue scale (VAS). The
      extent of gingival recession was measured using William's periodontal probe.
      After recording the initial baseline VAS scores, the patients were randomly
      divided into two groups according to the materials used in the study. The resin
      based dentin sealer in the test group was applied following the manufacture's
      recommendations. Water was used in the control (placebo) group. Hypersensitivity
      measurements on VAS were repeated 5 minutes, 7 and 30 days after the application
      of the materials. RESULTS: It was observed that the efficacy of the desensitizing
      material differed from placebo. The dentin sealer effectively reduced the root
      sensitivity. The statistically significant (p<0.001) decrease in the intensity of
      root sensitivity after the application of materials was noted in test and control
      groups. However, the difference in the reduction of pain intensity between the
      groups was significant and remained such throughout the study period. The root
      sensitivity on the day 7 and 30 in both groups showed little change compared to
      the measurements made right after the application of the materials. No
      significant difference in measurements of pain intensity in the presence of
      different extent of gingival recession was noted in none of the groups.
      CONCLUSION: The results of the study showed that dentin sealer used provided
      quick and effective reduction in root sensitivity after the surgery and its
      desensitizing effect lasted beyond 30 days.

PMID- 16607062
TI  - Analysis of odontogenic cysts of the jaws.
AB  - In this study 850 cases of odontogenic cysts of the jaws, treated in Kaunas
      University of Medicine Hospital during the period of 1986-2004, were analyzed in
      order to evaluate the incidence of these cysts and other aspects of clinical and
      therapeutic interest such as their clinical features, changes they caused in the
      facial and mandible structures, and the teeth that had caused the pathology. Case
      histories of 455 men and 395 women had been analyzed. The age of the patients
      varied from 4 to 87 years, with the average of 35.8. More than half of the
      diagnosed cysts (63%) were present in the maxilla, 37% of them--in the mandible.
      The common complaints of the patients were bump, swelling, pain, discharge
      leaking from the fistula or alveolus after tooth extraction, increased teeth
      mobility, paresthesia; changes in the maxillofacial system - intraoral or facial
      asymmetry, inflated bone with sensation of an egg shell cracking revealed under
      palpation, swelling at the mucofacial fold, mobile teeth and fistula. While
      comparing the causative groups of antagonistic teeth in the maxilla and mandible,
      we found the proportion to be (in order from the right to the left): molars--1:1,
      premolars 1.3:1, fore teeth--3.3:1, fore teeth 3.8:1, premolars 1.2:1, molars
      0.7:1. Odontogenic cysts may be present in both sexes; maxillary cysts are 1.5
      times as frequent as mandibular cysts. The pathology may equally affect both
      sides of jaws, most cysts being diagnosed in the maxillary fore teeth area from
      tooth 13 to tooth 23. The following pairs of changes in maxillofacial system are
      frequently present: inflated body of bone or alveolus--increased mobility of
      teeth; the formed fistula--swelling at the mucofacial fold, swelling at the
      mucofacial fold--pain. The applied treatment of cysts was surgical--cystotomy or
      cystectomy.

PMID- 16607063
TI  - Changes in serum electrolyte levels and their influence on the incidence of
      atrial fibrillation after coronary artery bypass grafting surgery.
AB  - OBJECTIVE: Our study was designed to assess the incidence of atrial fibrillation,
      changes of serum electrolyte concentrations following coronary artery bypass
      grafting surgery. MATERIAL AND METHODS: After approval of Kaunas Region Ethics
      Committee for Biomedical Research and written informed consent of the patients
      the data of 82 patients undergoing elective coronary artery bypass grafting
      surgery in Kaunas Heart Center, Clinic of Cardiac Surgery, during the period of
      2004-2005 were analyzed. Serum potassium, sodium, ionized magnesium, ionized
      calcium, chloride and phosphate levels were measured before cardiopulmonary
      bypass, on arrival to intensive care unit and 18-20 hours after the surgery.
      Cardiac rhythm was monitored throughout the study. All patients were divided into
      two groups. Group I (n=22) included patients with postoperative atrial
      fibrillation. Group II (n=60) included patients, who remained in sinus rhythm
      after the surgery. RESULTS: The overall incidence of atrial fibrillation was
      26.83%. The patients in group I were significantly older than in group II
      (68.27+/-6.09 and 64.20+/-9.32 years, respectively; p=0.025). Immediately after
      the surgery serum chloride concentration was higher in group I comparing to group
      II (111.91+/-4.48 and 105.17+/-5.73 mmol/l, respectively; p<0.001). Serum
      phosphate level was lower in group I (0.98+/-0.15 and 1.09+/-0.19 mmol/l,
      respectively; p=0.013). At 18-20 hours after the surgery in the group I ionized
      calcium was lower comparing to group II (0.97+/-0.06 and 1.00+/-0.05 mmol/l,
      respectively; p=0.021). Serum phosphate level was lower in group I also (0.81+/
      0.16 and 0.99+/-0.20 mmol/l, respectively; p<0.001). CONCLUSIONS: 1. The
      incidence of atrial fibrillation after coronary artery bypass surgery remains
      relatively high (26.83%). 2. Serum electrolyte concentration after coronary
      artery bypass grafting varies within normal ranges. 3. Patients with
      postoperative atrial fibrillation had higher chloride and lower phosphate
      concentration immediately after surgery and lower ionized calcium and phosphate
      level 18-20 hours after the surgery.

PMID- 16607064
TI  - [Multiple endocrine neoplasia type 2A].
AB  - Multiple endocrine neoplasia (MEN) type 2A, or Sipple syndrome, is a rare
      autosomal dominantly inherited syndrome, which is characterized as combination of
      medullary thyroid carcinoma, pheochromocytoma, primary hyperparathyroidism,
      sometimes with rarer inherited disorders like Hirschsprung disease and cutaneous
      lichen amyloidosis. Syndrome is caused by germinative mutations in c-ret
      protooncogene, which are typical for different MEN 2 syndromes. We report a
      clinical case of MEN 2A. A 43-year-old female patient was operated on for
      pheochromocytoma 7 years after diagnosis and treatment of spread medullary
      thyroid carcinoma. This is the most common combination of MEN 2A tumors.
      Diagnosis was based upon clinical data, tumors combinations and analysis of
      inherited endocrine pathology in first-line relatives. This syndrome has already
      been diagnosed in Lithuania, but in the last decade after determining the genetic
      basis of MEN 2 and applying modern genetic examinations in clinical praxis, the
      strategy of diagnostics and prophylaxis of this syndrome has changed and survival
      prognosis for patients with this syndrome has improved. Conception of
      pathogenesis and clinical features of MEN 2A syndrome, genetic selection of
      inheritors of this syndrome is one more step in early cancer diagnosis, which
      allows to use cancer prevention measures in time, to apply effective treatment
      and improve patients' prognosis. Reporting this clinical case of MEN 2A we aimed
      to pay attention of general practitioners to this rare, but in Lithuania
      diagnosed too, syndrome and its clinic, diagnostic, and treatment features.

PMID- 16607065
TI  - Seasonal differences in activities of rabbit liver tRNA and aminoacyl-tRNA
      synthetases specific for valine and arginine under myocardial ischemia.
AB  - The objective of this study was to examine the acceptor activities of tRNA for
      amino acids, valine and arginine, and the activities of the corresponding
      aminoacyl-tRNA synthetases of normal rabbit liver and 6, 12 and 24 h after
      experimental myocardial ischemia in different seasons of the year. MATERIAL AND
      METHODS: Male rabbits (2.5-3.5 kg) were used. Acute myocardial ischemia was
      induced by occlusion of the left anterior descending coronary artery. tRNA and
      aminoacyl-tRNA synthetases were isolated from control rabbit liver and 6, 12 and
      24 h after experimental myocardial ischemia in autumn (September and October) and
      winter (December and January). The acceptor activity of tRNA and the activity of
      valyl- and arginyl-tRNA synthetases were determined using 14C-labeled amino
      acids, valine and arginine. RESULTS: The results showed that acceptor activity of
      rabbit liver tRNA for valine and arginine under 6, 12 and 24 h experimental
      myocardial ischemia in autumn was higher by 24-35% than in winter. Activities of
      rabbit liver valyl- and arginyl-tRNA synthetases under 6, 12 and 24 h
      experimental myocardial ischemia in autumn were lower by 15-32% than in winter.
      No differences in the activity of tRNA and aminoacyl-tRNA synthetases between
      control groups of both seasons were observed. CONCLUSIONS: The experimental data
      suggest that acceptor activity of rabbit liver tRNA for valine and arginine and
      activity of valyl- and arginyl-tRNA synthetases under 6, 12 and 24 h experimental
      myocardial ischemia are different in autumn and winter. The decrease of acceptor
      activity of tRNA for valine and arginine after experimental myocardial ischemia
      correlates with an increase in the activity of valyl- and arginyl-tRNA
      synthetases both in autumn and winter. It may be part of the compensatory
      mechanism of the cell to keep synthesis of protein in a normal range under
      extreme conditions.

PMID- 16607066
TI  - Opinion of patients on accessibility of primary health care centers in Siauliai
      region.
AB  - This article presents the data about the accessibility of primary health care in
      Siauliai region and about factors related to the patients' perceived access to
      primary care. The survey was carried out in June 2004, in the context of a joint
      project of Kaunas University of Medicine and NIVEL, the Netherlands Institute of
      Health services research. Patients, treated in private and public health care
      centers in Siauliai region, took part in this survey. The majority of patients
      are positive about territorial accessibility of primary health care, indicating
      that it is easy to get to primary health care centers. Patients expressed a high
      level of satisfaction with the behavior of reception desk personnel. However,
      they are more critical about waiting time for the general practitioner's
      consultation: every third noted that they had to wait for far too long. The
      majority of respondents pointed out that general practitioners rooms and waiting
      corridors are convenient and comfortable, and that general practitioners have
      sufficient medical equipment. Most of the patients are very well informed and
      satisfied with the opening hours of primary health care centers. The main factors
      related to the patients' evaluations of primary health care accessibility were
      living place of patients and type of ownership of health care center. Patients
      living in the towns were less likely to evaluate the accessibility of primary
      health care centers positively, compared to those living in the city of Siauliai.
      Patients receiving health care services in private centers were much more
      positive about access to services than those receiving services in public
      centers.

PMID- 16607067
TI  - Monthly number of newborns and environmental physical activity.
AB  - In the last decades many studies have demonstrated the cosmophysical influences
      on human homeostasis. The aim of the study was to explore links between
      environmental physical activity--solar, geomagnetic, cosmic ray--and monthly
      number of newborns in general and, separately, for each gender. MATERIAL AND
      METHODS: The distribution of newborns' number (n=286,963) over 96 months in the
      Republic of Lithuania from 1995 to 2002 was compared with the monthly
      cosmophysical indices nine months before the month of delivery. For the
      comparison of gender ratio, other 52,289 newborns at the same time were studied
      in a big Israeli hospital. Pearson's correlation coefficients and their
      probabilities between the newborns' number and cosmophysical indices were
      established. RESULTS: A strong and significant inverse correlation of monthly
      newborns' number with monthly solar activity indices (r=-0.72, p<0.0001) and
      similar, but positive, with cosmic ray activity was shown (r=0.67, p<0.0001).
      CONCLUSIONS: The monthly number of newborns of both genders is strongly and
      significantly related to the level of monthly cosmic ray and, inverse, to solar
      activity indices nine months before the month of delivery. Geomagnetic activity
      was not significantly related to the monthly number of newborns. The subject and
      mechanism of these relationships needs further investigation.

PMID- 16607068
TI  - [Tendencies on ability related to competence education when realizing
      undergraduate public health study system].
AB  - The aim of this paper is to reveal tendencies on competence and ability education
      when realizing undergraduate public health study program in the interaction
      context of traditional and modern higher education features. Competence is
      implementation of qualification or the ability to act, conditioned by
      individual's knowledge, skills, motives, personal characteristics, and values.
      The integrated competence is necessary for the change of the internal and
      external work conditions; it is based on the integrity of behavior and knowledge
      that conditions the essential change of activity. The holistic competence is
      necessary for a new work development and the transfer of qualification to new
      situations; it is conditioned by holistic approach toward education. When
      researching undergraduate public health study program in the context of
      traditional and modern higher education features at Kaunas University of
      Medicine, the following problems were stated: insufficient qualities of student's
      self-analysis, self-directed learning and formation of communication skills;
      insufficient communication of teachers and students during study process; limited
      possibilities team work with representatives of other professions when solving
      problems of public health improvement.

PMID- 16607070
TI  - [Pathophysiology of acute spinal cord injury].
AB  - Spinal cord injury is one of the most devastating of all traumatic conditions
      that can be encountered by patients. Over the past years much research has been
      performed on elucidating the mechanisms of spinal cord injury. Experimental and
      clinical studies have suggested that acute spinal cord injury is a two-step
      process involving primary and secondary mechanisms. Primary injury of the spinal
      cord refers to the initial mechanical damage due to local deformation of the
      spine. Direct compression and damage of neural elements and blood vessels by
      fractured and displaced bone fragments or disc material occur after mechanical
      trauma. The secondary mechanism is initiated by the primary injury. The secondary
      mechanism includes a cascade of biochemical and cellular processes, such as
      electrolyte abnormalities, formation free radicals, vascular ischemia, edema,
      posttraumatic inflammatory reaction, apoptosis or genetically programmed cell
      death and another processes. This review describes the pathophysiology of acute
      spinal cord injury. Knowledge of the pathophysiology of the acute spinal cord
      injury is crucial for successful management of the patients with these injuries.

PMID- 16607071
TI  - The association between homocysteine and myocardial infarction is independent of
      age, sex, blood pressure, cholesterol, smoking and markers of inflammation: the
      Glasgow Myocardial Infarction Study.
AB  - Homocysteine is associated with both myocardial infarction and arterial wall
      inflammation. To establish whether homocysteine is associated with myocardial
      infarction after adjusting for age, sex, the major cardiovascular risk factors
      and inflammatory risk predictors (fibrinogen, C-reactive protein and interleukin
      6). A case-control study, using 364 myocardial infarction cases drawn from the
      north Glasgow MONICA study, 3-9 months after their event, and 383 controls drawn
      from the general population of the same geographical area. The odds ratio for
      myocardial infarction increased progressively across the four quarters of the
      homocysteine distribution, after adjusting for only age and sex or for the full
      adjustment (age, sex, smoking, systolic blood pressure, total cholesterol,
      fibrinogen, C-reactive protein and interleukin-6). The odds ratios produced by
      the two adjustments were similar. Comparing the top quarter with the bottom
      quarter of homocysteine, the odds ratio was 2.21 (95% confidence interval: 1.30
      3.76) after the full adjustment. The odds ratio for a 5 micromol/l increase in
      homocysteine was 1.12 (95% confidence interval: 1.01-1.24) after the full
      adjustment. CONCLUSION: This study suggests that homocysteine has an effect on
      cardiovascular risk over and above that of inflammatory markers and the major
      cardiovascular risk factors.

PMID- 16607072
TI  - Use of a new enzyme-linked immunosorbent assay for the detection of type 2N von
      Willebrand disease and its prevalence in an Indian population.
AB  - von Willebrand disease (VWD) is caused by qualitative or quantitative defects, or
      both, of the von Willebrand factor, a multimeric, high-molecular-weight
      glycoprotein. Type 2N VWD differs from other subtypes in that it shows normal
      primary haemostasis as all the routine tests performed for the diagnosis of VWD
      are normal. They present with defective coagulation, due to a moderate or severe
      deficiency of factor VIII, and consequently often they are misdiagnosed as either
      mild haemophilia A or type 1 VWD. Thus the actual prevalence of this subtype is
      not known in many of the populations. The differential diagnosis of this subtype
      is mainly based on the in-vitro capacity of plasma von Willebrand factor to bind
      exogenous factor VIII by immunoassay. However, most of the routine laboratories
      in developing countries do not have the testing facilities for type 2N VWD,
      mainly because of the cost of the reagents involved and the complexity of various
      assays reported. We report here the prevalence of type 2N VWD in an Indian
      population by developing a simple, not too expensive, user-friendly enzyme-linked
      immunosorbent assay technique and compared it with the reported technique of the
      factor VIII binding assay. Nine out of 97 VWD patients (10%) were found to be
      type 2N VWD using both the reported assay and the in-house ELISA; thus indicating
      that the prevalence of type 2N VWD is high in our population. The simple ELISA
      technique described here should be available in all routine laboratories in
      developing countries.

PMID- 16607073
TI  - Single nucleotide polymorphisms and haplotypes of protein C and protein S genes
      in the Thai population.
AB  - Protein C (PC) and protein S (PS) play key roles in an anticoagulant pathway in
      order to control the haemostatic system. We identified single nucleotide
      polymorphisms (SNPs) and/or haplotypes in the promotor and exons of the whole PC
      and PS genes and in the 3'-untranslated region of the PS gene in 55 Thai
      individuals. The PC gene revealed 10 haplotypes. One synonymous SNP at 2196 was
      found in the normal Thai population with a minor allele frequency of 4.90%. One
      homozygous mutation in exon 7, R147W, co-segregated with the synonymous SNP 2196
      (homozygote) of the PC gene, resulting in decreased PC activity and antigenic
      levels. The PS gene revealed three haplotypes with two frequent dimorphisms in
      exon 15 and the 3'-untranslated region. The most frequent haplotype in the PS
      gene was H3 (wild type). There was no correlation between the haplotypes of PC
      and PS genes with functional and antigenic levels of PC and PS.

PMID- 16607074
TI  - Lack of significant effect of low doses of aspirin on the concentrations of C
      reactive protein in a group of individuals with atherothrombotic risk factors and
      vascular events.
AB  - Atherothrombosis is associated with the presence of a microinflammatory response,
      usually monitored by the use of C-reactive protein (CRP) measurements. In the
      Physician Health Study it was suggested that individuals who benefit most from
      the treatment are those who have enhanced concentrations of this biomarker. The
      possibility was suggested that one of the mechanisms of action of aspirin in
      thrombotic prevention is through its anti-inflammatory properties in terms of
      reducing the concentration of CRP. We conducted a regression analysis in a cohort
      of 3888 apparently healthy individuals and those with atherothrombotic risk
      factors and vascular events, 370 of whom were under the treatment of low doses
      (<or= 325 mg/day) of aspirin. The significant determinants of CRP concentrations
      included body mass index, oral contraceptives, hormonal replacement therapy,
      gender, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, triglycerides, physical activity, age, smoking status and the
      presence of diabetes mellitus but not the use of low dose of aspirin. We conclude
      that the use of low doses (<or= 325 mg/day) of aspirin does not have a
      significant role in the modulation of CRP concentrations in apparently healthy
      individuals and those with atherothrombotic risk factors and vascular events. The
      anti-atherothrombotic activity of this drug is probably not mediated through a
      significant reduction of the concentration of this protein.

PMID- 16607075
TI  - Risk of recurrent venous thrombosis in patients with G20210A mutation in the
      prothrombin gene or factor V Leiden mutation.
AB  - The impact of the G20210A prothrombin mutation, factor V Leiden and 677T mutation
      of methylene tetrahydrofalate reductase (MTHFR) in recurrent deep venous
      thrombosis (DVT) is not so clear. We have prospectively monitored 259 patients
      following a first episode of DVT in order to determine which factors influence
      the development of a recurrent event. Several clinical and biological factors
      together with the genetic polymorphisms of factor V Leiden, G20210A prothrombin
      and 677T MTHFR were assessed. During a median follow-up of 786 patient-years, 27
      patients (14%) developed one objective episode of recurrent venous thrombosis.
      The carriers of a double defect, homozygous or double heterozygous for factor V
      Leiden and G20210A, had an increased risk after a first episode of DVT, while
      patients who were isolated heterozygous for factor V Leiden or G20210 had a risk
      of recurrent DVT similar to patients who had neither mutation (annual incidence
      of 12.1, 3.1, 2.9 and 2.8%). The 677T MTHFR mutation alone or combined with
      hyperhomocysteinemia was not associated with an increased risk of recurrent
      events. The development of proximal DVT (P=0.01) and the presence of a double
      defect (P=0.01) were the only two risk factors independently associated with a
      high recurrence ratio in the multivariate analysis. Thus, the annual incidence of
      DVT recurrence in patients without any of these two risk factors was only 0.6%
      (95% confidence interval, 0.2-0.9). We have identified a group of patients with
      DVT but at very low risk of re-thrombosis in whom an extended secondary
      thromboprophylaxis should be carefully considered.

PMID- 16607076
TI  - The effect of N-acetylcysteine on blood coagulation and platelet function in
      patients undergoing open repair of abdominal aortic aneurysm.
AB  - N-acetylcysteine (NAC) may offer renal and hepatic protection during surgery, but
      in experimental studies it has been shown to impair coagulation. Since very
      little is known about the effects of NAC on blood coagulation in surgical
      patients, we studied its effects during abdominal aortic reconstruction. NAC (a
      bolus of 150 mg/kg followed by a continuous 24-h infusion of 150 mg/kg) or the
      same volume of placebo was given intravenously, in a randomized double-blinded
      fashion, to 20 patients undergoing abdominal aortic aneurysm repair. The
      haematocrit, platelet count, prothrombin time, thromboelastometry, and platelet
      aggregation were studied during and after surgery. Total blood loss was also
      measured. The median (25th-75th percentiles) decrease of the prothrombin time
      value was 33.0% (30-37%) after NAC treatment and 6.5% (4-8%) after placebo
      (P<0.001). Postoperative prothrombin time values remained lower in the patients
      receiving NAC. In thromboelastometry tracings the coagulation time was more
      prolonged after the bolus of NAC (P=0.02). Platelet aggregation induced with
      adenosine diphosphate decreased after NAC but not after placebo. Low prothrombin
      time values before and after bolus infusions were associated with increased blood
      loss (P=0.008 and P=0.015, respectively). NAC has anticoagulant and platelet
      inhibiting properties in patients undergoing major vascular surgery. This
      abnormal haemostatic activity should be considered when NAC is administered to
      patients with increased bleeding risk.

PMID- 16607077
TI  - Interleukin-6 -174 G/C promoter polymorphism and effects of fenofibrate and
      simvastatin on inflammatory markers in hypercholesterolemic patients.
AB  - To evaluate whether the interleukin-6 (IL-6) -174 G/C polymorphism might alter
      the effects of micronized fenofibrate or simvastatin therapy on inflammatory
      markers, we measured IL-6, C-reactive protein, CD40 ligand, adhesion molecules, P
      selectin and monocyte chemoattractant protein-1 in hypercholesterolemic patients
      both before and after a 30-day treatment. Serum IL-6 levels were significantly
      higher in patients with the GC or CC genotypes (P=0.04). The presence of the C
      allele was associated with greater absolute reduction of IL-6 levels (P=0.04)
      following fenofibrate treatment. There was no significant association between the
      -174 G/C IL-6 polymorphism and the effects of simvastatin treatment. A
      relationship between the -174 G/C IL-6 polymorphism and the anti-inflammatory
      action of fenofibrate reported might be useful in the optimization of the
      treatment regimen in patients receiving this class of drugs.

PMID- 16607078
TI  - Cold storage of citrated whole blood induces drastic time-dependent losses in
      factor VIII and von Willebrand factor: potential for misdiagnosis of haemophilia
      and von Willebrand disease.
AB  - This study investigates the effect of pre-analytic storage conditions on the
      laboratory evaluation of von Willebrand disease (VWD) and haemophilia. Samples
      from healthy controls and patients with VWD were stored as whole blood and as
      separated plasma, both at room temperature and on crushed ice, for two different
      time periods (3 or 6 h). In samples from healthy individuals (n=10) and in
      patients with suspected type 1 VWD (n=10), storage of whole blood on ice caused a
      drastic time-dependent decrease in von Willebrand factor (VWF):ristocetin
      cofactor activity, in VWF:antigen activity and factor VIII activity (mean+/-SD)
      to 35+/-18, 55+/-23 and 53+/-15% of baseline levels after 6 h storage,
      respectively. Patients with type 2 VWD and non-detectable VWF:ristocetin cofactor
      activity did not demonstrate such drastic cold-induced losses in VWF and factor
      VIII levels. Storage of plasma caused only minor changes in VWF levels. The cold
      induced loss in VWF might thus depend on the presence of platelets and of high
      molecular weight VWF. Chilling of platelets induces a clustering of the
      glycoprotein Ib subunit. We therefore hypothesize that cold-induced loss in VWF
      might be due to a cold-promoted binding of VWF to glycoprotein VWF receptor Ib
      alpha. These results suggest a serious potential for misdiagnosis of haemophilia
      or VWD due to inappropriate pre-analytical handling of blood.

PMID- 16607079
TI  - Unchanged global fibrinolytic capacity during the course of hematopoietic stem
      cell transplantation.
AB  - Hemostatic changes due to vascular endothelial damage are seen during the course
      of hematopoietic stem cell transplantation (HSCT). The fibrinolytic response to
      ongoing hemostatic activation in HSCT remains to be elucidated. Global
      fibrinolytic capacity (GFC) is a novel method, which reflects the amount of
      generated D-dimer when fibrinolysis of a freeze-dried fibrin clot is stopped by
      introducing aprotinin. GFC is sensitive to all the factors involved in the
      process of fibrinolysis. The aim of this study was to serially assess GFC at
      certain critical time points (days -1, +7, +14, +21 prior to and following stem
      cell infusion) during the course of HSCT. The study group comprised 16 patients
      with hematological malignancies (11 women, five men; median age 32+/-9 years) in
      whom HSCT had been performed. Thirty healthy adults (21 women, nine men; median
      age 31+/-7 years) served as controls. In this study, global fibrinolytic
      response, as reflected by GFC, was unchanged despite ongoing hemostatic
      activation, as indicated by D-dimer, moreover GFC remained stable, despite the
      development of thrombocytopenia associated with HSCT prior to platelet
      engraftment. Our results indicate that a global fibrinolytic response was
      impaired as a compensatory response to endothelial activation and to other
      hemostatic changes seen in HSCT. Further studies in larger HSCT populations are
      warranted to better understand the implications of these findings.

PMID- 16607080
TI  - Nucleotide changes around the splicing acceptor of intron 24 in the factor VIII
      gene and its impact on splicing.
AB  - Nucleotide 6724 of the factor VIII gene harbors a polymorphism of low frequency.
      A report from Taiwan claimed that 97.9% of the 83 alleles examined were of the A
      nucleotide at this position, which is quite different to the data from Western
      populations. Furthermore, this nucleotide is the start of exon 25, located in
      juxtaposition to the splicing acceptor of intron 24. We wonder if the nucleotide
      change at this location might have any effect on the splicing process of pre
      mRNA. Using genomic DNA with direct sequencing of the polymerase chain reaction
      amplified intron 24/exon 25 junction site, we found that 59 of the 60 patient
      samples were of the GTG sequence at nucleotides 6724-6726. The polymorphism is
      similar between populations in Taiwan and Western countries. The sequence of
      intron 24 around the splicing acceptor was always TCCAACTCTATTGCCCTCAG (-20 to 
      1), except for one hemophiliac patient who had a mutation in which the absolute
      consensus AG doublet of the intron 24 splicing acceptor changed to the AA
      dinucleotide. Owing to the mutation, exon 24 was erroneously spliced to exon 26,
      and exon 25 was skipped. This finding further testifies to the importance of the
      invariant AG dinucleotide in the example of the factor VIII gene.

PMID- 16607081
TI  - Massive pulmonary embolism with cardiac arrest after an intracardiac
      electrophysiological study: a strong case for venous thromboprophylaxis.
AB  - A 47-year-old woman was referred to our hospital for an intracardiac
      electrophysiological study. The procedure was complicated by cardiac arrest due
      to massive pulmonary embolism, which only successfully resolved after the
      administration of a thrombolytic agent. This case suggests that there is a real
      risk of venous thromboembolism in certain patients during electrophysiological
      studies. Therefore, a consensus should be reached concerning the prevention of
      venous thromboembolism during these procedures.

PMID- 16607082
TI  - Hepatic vein thrombosis leading to fulminant hepatic failure in a case of acute
      non-promyelocytic myelogenous leukemia.
AB  - Budd-Chiari syndrome is a rare disease due to occlusion of the hepatic veins
      often presenting with acute liver failure. Common causes of Budd-Chiari syndrome
      are chronic myeloproliferative disorders, while acute leukemia has been
      associated with hepatic vein thrombosis in only two cases in the literature to
      date. We report a case of Budd-Chiari syndrome complicating a non-promyelocytic
      acute myelogenous leukemia leading to fulminant hepatic failure.

PMID- 16607083
TI  - Novel fibrinogen mutation (gamma 313 Ser-->Asn) associated with
      hypofibrinogenemia in two unrelated families.
AB  - Congenital hypofibrinogenemia is a rare disorder caused by a number of different
      mutations in the fibrinogen genes. The aim of the study was the elucidation of
      molecular defects in two unrelated families with hypofibrinogenemia. DNA samples
      from the patients were screened for mutations in the fibrinogen genes by direct
      sequencing of polymerase chain reaction-amplified gene segments. Isolated plasma
      fibrinogen was studied by sodium dodecyl sulfate electrophoresis and electrospray
      ionization mass spectrometry in order to detect variant polypeptides. Fibrin
      polymerization was analyzed both in plasma and using purified fibrinogen samples.
      A novel mutation in the FGG gene (G7590A) was found in all patients from the two
      families with hypofibrinogenemia. This mutation causes the amino acid exchange
      313 Ser-->Asn in the gamma chain. When plasma fibrinogen from a heterozygous
      individual was analyzed for the presence of variant gamma chains by reverse-phase
      high-performance liquid chromatography and electrospray ionization mass
      spectrometry, only normal gamma chains could be detected. The molecular defect
      affecting an evolutionary highly conserved amino acid residue in human fibrinogen
      interferes with plasma expression of the variant molecules and is causative for
      the observed hypofibrinogenemic phenotype.

PMID- 16607084
TI  - Identification of five novel mutations in the factor XI gene (F11) of patients
      with factor XI deficiency.
AB  - Factor XI (FXI) deficiency is an inherited autosomal recessive disorder
      associated with bleeding of variable severity. However, many cases of dominant
      disease transmission have been recently described. This disorder is rare in the
      general population, whereas it is commonly found in individuals of Ashkenazi
      Jewish ancestry. This study reports the molecular genetic analysis of FXI
      deficiencies in 11 unrelated families of different origin. Five novel mutations
      have been identified. Severe FXI deficiency of two unrelated patients resulted
      from two novel mutations: one deletion (960-961delGT) in exon 9 predicting a
      frameshift, and a Ser-4Leu mutation located in the signal peptide. In addition,
      three novel missense mutations associated with partial FXI deficiency have been
      identified: Cys122Tyr, Glu297Lys and Glu579Lys.

PMID- 16607085
TI  - Elastic modulus-based thrombelastographic quantification of plasma clot
      fibrinolysis with progressive plasminogen activation.
AB  - Thrombelastographic detection of fibrinolysis has been critical in the
      identification and treatment of coagulopathy in many perioperative settings.
      However, the fibrinolytic assessments have been at best non-parametric, amplitude
      based determinations (e.g. estimated % lysis, clot lysis time or clot lysis
      rate). Recognizing this limitation, a methodology was developed to measure the
      onset, speed and extent of clot disintegration by changes in elastic modulus
      derived from the amplitude. Using this approach, our goal was to characterize the
      clot disintegration kinetics of progressive plasminogen activation with tissue
      plasminogen activator (tPA) and to determine the extent of inhibition of
      fibrinolysis mediated by tPA with aprotinin and activated factor XIII. While the
      estimated % lysis and clot lysis time were significantly affected by tPA (0-300
      U/ml), elastic modulus-based analyses in a more activity-specific fashion
      demonstrated significantly decreased onset, increased rate and increased extent
      of fibrinolysis. Furthermore, aprotinin was found to inhibit the onset, rate and
      extent of fibrinolysis in an activity-dependent fashion, whereas activated factor
      XIII was noted to enhance the speed of onset of clot growth and delay the onset
      of fibrinolysis. In summary, our results serve as the rational basis to utilize
      this elastic modulus-based approach to quantify the extent of fibrinolysis in
      clinical and laboratory settings, as well as potentially guiding antifibrinolytic
      therapy.

PMID- 16607086
TI  - Basilar artery dolichoectasia with partial thrombosis.

PMID- 16607087
TI  - Venous and arterial thrombosis following administration of intravenous
      immunoglobulins.

PMID- 16607088
TI  - Plasma D-dimer variation following elective orthopedic surgery.

PMID- 16607089
TI  - Observational studies and clinical trials of menopausal hormone therapy: can they
      both be right?

PMID- 16607090
TI  - What do we think about cognition and menopause?

PMID- 16607091
TI  - Potential importance of early initiation of hormone therapy for cognitive
      benefit.

PMID- 16607092
TI  - Is testosterone or estradiol the hormone of desire? A novel study of the effects
      of testosterone treatment and aromatase inhibition in postmenopausal women.

PMID- 16607093
TI  - Prevalence of hypoactive sexual desire disorder in postmenopausal women: results
      from the WISHeS Trial.

PMID- 16607094
TI  - Increased longevity in older users of postmenopausal estrogen therapy: the
      Leisure World Cohort Study.
AB  - OBJECTIVE: To examine the effect of postmenopausal estrogen therapy (ET),
      including duration and recency of use, on all-cause mortality in older women.
      DESIGN: As part of a prospective cohort study of residents of a California
      retirement community begun in the early 1980s, Leisure World Cohort women (median
      age, 73 y) completed a postal health survey including details on ET use and were
      followed up for 22 years (1981-2003). Age- and multivariate-adjusted risk ratios
      (RR) and 95% CIs were calculated using proportional hazard regression. RESULTS:
      Of the 8,801 women, 6,626 died during follow-up (median age, 88 y). ET users had
      an age-adjusted mortality rate of 52.9 per 1,000 person-years compared with 56.5
      among lifetime nonusers (RR = 0.91; 95% CI, 0.87-0.96). Risk of death decreased
      with both increasing duration of ET and decreasing years since last use (P for
      trend <0.001). The risk was lowest among long-term (> or =15 y) users (RR = 0.83;
      95% CI, 0.74-0.93 for 15-19 y and RR = 0.87; 95% CI, 0.80-0.94 for 20+ y). For
      long-term users, the age-adjusted mortality rate was 50.4 per 1,000 person-years.
      Lower-dose users (< or =0.625 mg) had a slightly better survival rate than higher
      dose users (RR = 0.84; 95% CI, 0.78-0.91 vs RR = 0.91; 95% CI, 0.83-0.97). Risk
      did not differ by route of administration (P = 0.56). Further adjustment for
      potential confounders had little effect on the observed RRs for ET. CONCLUSION:
      Long-term ET is associated with lower all-cause mortality in older women.

PMID- 16607095
TI  - Cognitive function across the life course and the menopausal transition in a
      British birth cohort.
AB  - OBJECTIVE: Despite biological plausibility, relationships between menopause and
      cognitive function are inconsistent. We investigated whether menopause status and
      menopause age were associated with general cognitive ability, verbal memory, and
      visual search speed and concentration in a large cohort of women while
      considering vasomotor and psychological symptoms, previous childhood and adult
      measures of cognitive function, lifetime socioeconomic circumstances, educational
      attainment, lifestyle factors, and chronic diseases. DESIGN: A nationally
      representative British cohort of 1261 women born in March 1946 and all aged 53
      years at cognitive testing, with prospective information on previous cognitive
      function, menopausal characteristics, and potential confounders. RESULTS: There
      was only weak evidence of the effect of natural menopause on cognitive function
      and no evidence of any effects of hormone therapy use or hysterectomy status.
      There was a trend across the phases of the natural menopausal transition (pre-,
      peri-, and postmenopause) for the National Adult Reading Test (P = 0.005) and
      search speed and concentration (P = 0.042), with postmenopausal women having the
      lowest cognitive function, but there was no trend in verbal memory. Variation in
      vasomotor and psychological symptoms did not explain these trends. In
      postmenopausal women, there was a positive trend across menopause age for verbal
      memory (P = 0.004) and a weak positive trend for the National Adult Reading Test
      (P = 0.052), with women who reached menopause later having higher cognitive
      function. Previous cognitive function generally explained the associations, which
      were further weakened by adjusting for socioeconomic and educational confounders.
      One exception was the association between the natural menopause transition and
      search speed and concentration, which remained after adjustment for these
      factors. CONCLUSION: Menopause adversely affects cognitive function, but this
      effect may be largely explained by premenopausal cognitive function. These
      findings suggest that common environmental or genetic factors, operating through
      long-term or lifelong hormonal mechanisms, may influence the timing of natural
      menopause and lifetime cognitive function.

PMID- 16607096
TI  - Hormone therapy, timing of initiation, and cognition in women aged older than 60
      years: the REMEMBER pilot study.
AB  - OBJECTIVE: The aim of this pilot study was to assess any trends related to the
      timing of initiation, and duration, of hormone therapy (HT) use on cognitive
      function to facilitate the design and power calculations for a future large
      cohort study entitled Research into Memory, Brain function and Estrogen
      Replacement (REMEMBER). DESIGN: A total of 428 women aged older than 60 years
      were recruited from a computer-generated random selection of Adelaide households.
      Demographic and lifestyle characteristics, and HT use history were recorded and
      confirmed. The Center for Epidemiological Studies-Depression score was used to
      assess mood. Cognitive tests were administered measuring global cognition (Mini
      Mental State Examination), attention and concentration (Trail Making Test Parts A
      and B), verbal learning and memory (Consortium to Establish a Registry for
      Alzheimer's Disease [CERAD] word list immediate and delayed recall), and verbal
      expression (letter fluency [FAS], category fluency [Animals], and the Boston
      Naming Test [short form]). Analyses were adjusted for age, education, mood, body
      mass index, smoking, alcohol intake, and history of cerebrovascular disease. HT
      use was defined as the use of systemic HT for at least 1 year. Early initiation
      of HT use was defined as commencement of HT before age 56 years for women with a
      uterus and ovaries, or within 5 years of a hysterectomy and bilateral
      oophorectomy. Late initiation of HT use was defined as HT commencing after these
      times. RESULTS: Early initiators of HT performed better than late initiators on
      the Mini-Mental State Examination (P = 0.04) and were faster than never users on
      the Trail Making Test Part A (P = 0.02). Women aged 70-79 years who initiated HT
      early performed better on the FAS test than never users (P = 0.0008). Late
      initiators performed worse than never users on the Mini-Mental State Examination
      (P = 0.09), and on the FAS test in the 60-69 year (P = 0.06) and 80 years and
      older (P = 0.095) age groups. However, late initiators performed better than
      never users on the FAS test in the 70-79 year age group (P = 0.015). HT users of
      less than 11 years (P = 0.09), HT users of more than 11 years (P = 0.04), and
      estrogen-only users (P = 0.024) performed faster than never users on the Trail
      Making Test Part A. Combined estrogen plus progestin users performed better than
      never users on the Boston Naming Test short form (P = 0.07). CONCLUSIONS: For
      some cognitive domains, early initiation of HT from around menopause may be
      beneficial, and initiation of HT in late menopause may be detrimental. The timing
      of the initiation of HT seems critical. To fully test these hypotheses and to
      further examine these trends by route and type of HT regimen in this population,
      a study size of 2,500 women would be required.

PMID- 16607097
TI  - Effects of aromatase inhibition on sexual function and well-being in
      postmenopausal women treated with testosterone: a randomized, placebo-controlled
      trial.
AB  - OBJECTIVE: The extent to which aromatization of testosterone (T) to estradiol is
      required for the observed effects of testosterone therapy on sexual function and
      well-being are not known. Therefore, the authors investigated the effects of
      aromatase enzyme inhibition on sexual function, well-being, and mood in estrogen-
      and T-replete postmenopausal women in a double-blind, randomized, placebo
      controlled study. DESIGN: Postmenopausal women using transdermal estrogen therapy
      for at least 8 weeks and reporting low sexual satisfaction (score <42 for the
      Sabbatsberg Sexual Self-rating Scale [SSS]) with a total T value of less than 1.2
      nmol/L were treated with 400 muL of a 0.5% T gel (total dose 2 mg) and were
      randomly assigned to receive treatment with either 2.5 mg/day of letrozole or an
      identical placebo tablet. Women were assessed at baseline (week -2) and at 0, 4,
      8, and 16 weeks. Sexual function was assessed with the SSS, well-being was
      assessed with the Psychological General Well-being Index, and mood was assessed
      with the Beck Depression Inventory at 0 and 16 weeks. Eighty-one women were
      screened, 76 were randomly assigned to a treatment group, and 30 in each group
      completed the study. Because this was a mechanistic study, only the 60 women who
      completed the study per protocol were included in the final analysis. RESULTS:
      Total T and calculated free T increased from baseline in both groups, with no
      difference between groups. At 16 weeks, estradiol, sex hormone-binding globulin,
      fasting lipids, lipoprotein(a), and C-reactive protein did not differ from
      baseline or between groups. Significant increases in total Sabbatsberg Sexual
      Self-rating Scale scores, total Psychological General Well-being Index scores,
      and a reduction in Beck Depression Inventory scores from baseline to 16 weeks was
      seen for both treatment groups, with no effect of treatment allocation. No
      adverse treatment effects were reported. CONCLUSIONS: Increases in total and free
      T in the physiologic range in postmenopausal women were associated with improved
      sexual satisfaction, well-being, and mood. In this study, aromatase inhibition
      did not influence any of these outcomes. Short-term transdermal T therapy did not
      modify fasting lipids, lipoprotein(a), or C-reactive protein.

PMID- 16607098
TI  - Hypoactive sexual desire disorder in postmenopausal women: US results from the
      Women's International Study of Health and Sexuality (WISHeS).
AB  - OBJECTIVE: To determine the prevalence of hypoactive sexual desire disorder
      (HSDD) among US women by reproductive status and age and to explore the
      correlates of sexually related distress. DESIGN: The Women's International Study
      on Health and Sexuality questionnaire was mailed to a national sample of US women
      in 2000. The survey included validated questionnaires: the Short Form-36, which
      measures overall health status; the Profile of Female Sexual Function, which
      assesses sexual desire; and the Personal Distress Scale, which measures distress
      caused by low desire. Four groups of women were studied: surgically
      postmenopausal, aged 20 to 49 years and 50 to 70 years; premenopausal, aged 20 to
      49 years; and naturally postmenopausal, aged 50 to 70 years. Clinically derived
      cutoff Profile of Female Sexual Function and Personal Distress Scale scores were
      used to classify women with HSDD and determine its prevalence. The relations
      between sexual desire and frequency of sexual activity or relationship
      satisfaction were assessed. Overall health status of HSDD women and women with
      normal desire were compared. RESULTS: The prevalence of HSDD ranged from 9% in
      naturally postmenopausal women to 26% in younger surgically postmenopausal women.
      The prevalence of HSDD was significantly greater among surgically postmenopausal
      women, aged 20 to 49 years, than premenopausal women of similar age, whereas
      there were no significant differences in the prevalence between surgically
      postmenopausal women, aged 50 to 70 years, and naturally postmenopausal women.
      For many women, HSDD was associated with emotional and psychological distress as
      well as significantly lower sexual and partner satisfaction. HSDD was also
      associated with significant decrements in general health status, including
      aspects of mental and physical health. CONCLUSIONS: HSDD is prevalent among women
      at all reproductive stages, with younger surgically postmenopausal women at
      greater risk, and is associated with a less active sex life and decreased sexual
      and relationship satisfaction.

PMID- 16607099
TI  - Effect of tibolone administration on central and peripheral levels of
      allopregnanolone and beta-endorphin in female rats.
AB  - OBJECTIVE: We evaluated the effects of tibolone oral administration on
      neuroendocrine function by investigating the modulation exerted by tibolone
      administration on allopregnanolone and central and peripheral beta-endorphin
      (beta-EP) levels in ovariectomized rats. DESIGN: Female Wistar rats (N = 64) were
      included: 48 rats were ovariectomized, 8 cycling rats were included as controls,
      and 8 cycling rats were treated with placebo. The ovariectomized animals were
      divided into six groups: untreated rats and those that received 14-day oral
      treatment with either placebo, estradiol valerate (E2V) 0.05 mg/kg/d, or tibolone
      (0.1, 0.5, or 2 mg/kg/d. beta-EP levels were assessed in the frontal lobe,
      parietal lobe, hippocampus, hypothalamus, anterior pituitary, neurointermediate
      pituitary, and plasma, whereas allopregnanolone levels were measured in the
      frontal lobe, parietal lobe, hippocampus, hypothalamus, anterior pituitary,
      adrenal glands, and serum. RESULTS: The administration of tibolone (0.5 and 2
      mg/kg/d) in ovariectomized rats induces a significant increase of
      allopregnanolone in the frontal lobe, parietal lobe, hippocampus, hypothalamus,
      whereas in serum a significant increase of allopregnanolone occurs only with the
      dose of 2 mg/kg/d, a significant decrease in allopregnanolone levels occurs in
      the adrenal glands. No changes occurred in the anterior pituitary. Tibolone doses
      of 0.5 and 2 mg/kg/d induced a significant increase in beta-EP content in the
      frontal lobe, hypothalamus, and neurointermediate lobe; and, at doses of 2
      mg/kg/d, in the parietal lobe, anterior pituitary, and plasma, without changes in
      the hippocampus. Compared with E2V, 0.5 mg/kg/d tibolone showed a similar effect
      on allopregnanolone and beta-EP in most brain regions. CONCLUSIONS: Tibolone
      administration affects beta-EP and allopregnanolone levels, playing a role as a
      neuroendocrine modulator.

PMID- 16607100
TI  - Endogenous androgen levels and well-being: differences between premenopausal and
      postmenopausal women.
AB  - OBJECTIVE: We investigated whether there is a relationship between androgens
      levels and well-being in pre- and postmenopausal women. DESIGN: We randomly
      recruited 1423 women aged 18 to 75 years from the community via the electoral
      roll. Each provided a morning blood sample and completed the Psychological
      General Well Being Index questionnaire on the same day. Women were excluded if
      they took medication for any psychiatric illness, had abnormal thyroid function,
      or had documented polycystic ovarian syndrome. Analysis was by linear regression
      for well-being, including demographic and lifestyle variables as well as serum
      levels of androgens. RESULTS: We included 1224 women in the analysis. Being
      partnered was positively associated with well-being in premenopausal women. In
      postmenopausal women, well-being was positively related to age and exercising,
      whereas smoking, obesity, and postmenopausal hormone therapy use were each
      negatively associated with well-being. None of the measured androgens (total and
      free testosterone, dehydroepiandrosterone sulfate, and androstenedione) made an
      independent contribution to well-being in postmenopausal women (n = 603).
      However, for premenopausal women (n = 621), levels of dehydroepiandrosterone
      sulfate were independently and positively associated with the domain score for
      vitality. CONCLUSIONS: Our findings do not support an important independent role
      for androgens as determinants of well-being in postmenopausal women. That
      dehydroepiandrosterone sulfate alone is associated with greater vitality in
      premenopausal women is of interest but requires further evaluation as an a priori
      hypothesis in another study.

PMID- 16607101
TI  - Estradiol and phytoestrogens differently influence the rodent postmenopausal
      mammary gland.
AB  - OBJECTIVE: In the following study, we investigated treatment-related changes in
      mammary gland histomorphology and structure after the administration of soy to
      adult virgin ovariectomized (OVX) female rats. Additionally, mammary receptor
      regulation was extensively evaluated by immunohistochemical analysis, and tissue
      proliferative activity analyzed by cell nuclear proliferating antigen expression
      (Ki67). DESIGN: OVX rats were treated, for 6 weeks, with either the vehicle, the
      soy extract (SSE 100 mg/kg/d PO), or 17beta-estradiol (0.5 mg/kg/d PO); a sham
      control group (SHAM) was also included in the study. When killed, mammary glands
      were collected and subsequently processed for light microscopy or
      immunohistochemistry. Immunoreactivity was quantified by a scoring system that
      took into account both the percentage of positive cells and the intensity of the
      staining. RESULTS: The 17beta-estradiol--treated rats had stimulated mammary
      glands compared with OVX rats, with an average lobulo-alveolar development not
      different from the SHAM controls. Only a partial regression of the glandular
      atrophy was observed in OVX rats receiving 100 mg/kg/d SSE, with a histological
      appearance between that of the OVX and SHAM controls. No significant changes were
      observed among experimental groups in the median ERalpha scores of the epithelial
      compartment (score of 3 in all groups); in the stromal compartment, a tendency
      toward decreased expression was seen with 17beta-estradiol rats compared with OVX
      controls (scores of 2 and 5, respectively). A significant reduction in ERbeta
      immunostaining was observed in the mammary glands of SSE-treated rats, in both
      epithelium and stroma (scores of 4 and 3, respectively), compared with those of
      OVX controls (score of 8 in both compartments). The ERbeta receptor status was
      not significantly affected by 17beta-estradiol. Compared with OVX rats (score of
      1), PR expression was up-regulated by 17beta-estradiol (score of 6), whereas an
      ovariectomy-like pattern was observed after the administration of SSE (score of
      0). Ki67 immunoreactivity in the epithelium and stroma was increased by the
      administration of 17beta-estradiol (scores of 4 and 5, respectively) and was
      unchanged after SSE treatment (scores of 0 and 2, respectively), compared with
      OVX controls (scores of 1 and 2, respectively). CONCLUSIONS: The differences
      observed in the histological pattern, hormonal receptor status regulation, and
      Ki67 modulation suggest a different role for phytoestrogens and 17beta-estradiol
      in postmenopausal rodent mammary glands.

PMID- 16607102
TI  - Medroxyprogesterone acetate inhibits the cardioprotective effect of estrogen in
      experimental ischemia-reperfusion injury.
AB  - OBJECTIVE: Results from recent clinical trials of estrogen and progestogen
      therapy (EPT) suggest that some progestogens may interfere with the
      cardiovascular benefits of estrogen (E). The aim of this study was to investigate
      whether medroxyprogesterone acetate (MPA) modifies the protective effect of E in
      experimental ischemia-reperfusion (IR) injury in vivo and in vitro in the rat.
      DESIGN: Ovariectomized female Wistar rats (250-280 g, n = 61) received E, MPA, E
      and MPA, or placebo subcutaneously. Fourteen days later, hearts were isolated and
      perfused with Krebs Henseleit for in vitro experiments or left in situ for in
      vivo experiments. In both cases, the left coronary artery was occluded for 45
      minutes, followed by 2 hours of reperfusion. RESULTS: In vivo E significantly
      reduced the necrotic zone of reperfused hearts (21.8% +/- 1.7% of area at risk)
      compared with placebo (42.8% +/- 4.8% area at risk; P < 0.05). This protection
      was reversed by co-administration of MPA with E (necrotic zone 38.2% +/- 6.1%
      area at risk). The influence of E on neutrophil infiltration was demonstrated by
      its ability to reduce myocardial myeloperoxidase activity (0.2 +/- 0.1 U/g
      tissue) relative to placebo (1.3 +/- 0.5 U/g tissue; P < 0.05). Myocardial
      myeloperoxidase activity was significantly increased to 1.1 +/- 0.3 U/g tissue in
      rats receiving E and MPA. However, MPA also reversed the protective effect of E
      in neutrophil-free buffer-perfused hearts, suggesting that additional mechanisms
      are involved. CONCLUSION: In this study, we showed that the administration of MPA
      can inhibit the effects of E that lead to protection of the myocardium from
      reperfusion injury and that this involves both neutrophil-dependent and
      neutrophil-independent mechanisms.

PMID- 16607103
TI  - Exercise training attenuates cardiovascular adverse remodeling in adult
      ovariectomized spontaneously hypertensive rats.
AB  - OBJECTIVE: To study the combined effects of ovariectomy and regular exercise
      training on hypertension and on cardiac and aortic remodeling in spontaneously
      hypertensive rats (SHR). DESIGN: Three-month-old female spontaneously
      hypertensive rats (SHR) were ovariectomized (ovx) or were left intact (int) and
      divided in four groups (n = 7): sedentary (sed-ovx), exercise-trained (ex-ovx),
      sedentary intact (sed-int), and exercise-trained intact (ex-int). The exercise
      protocol was performed on a motor treadmill for 13 weeks. Blood pressure (BP),
      left ventricular myocardium and aortic wall were studied by light microscopy and
      stereology. RESULTS: Exercise-trained SHR showed a BP reduction of more than 15%
      compared with the matched sedentary SHR (sed-int: 210 +/- 5 mm Hg, sed-ovx: 225
      +/- 4 mm Hg, ex-int: 178 +/- 2 mm Hg, ex-ovx: 180 +/- 3 mm Hg, P < 0.001).
      Ovariectomy caused adverse cardiac and aortic wall remodeling, including
      cardiomyocyte hypertrophy, myocardial interstitial reparative fibrosis and
      vascularization impairment with loss of cardiomyocytes, and aortic tunica media
      hypertrophy. Exercise training showed beneficial effects, mainly reduced BP,
      decreased cardiac hypertrophy due to hypertension, and increased myocardial
      vascularization. Ovariectomy accelerated cardiomyocyte loss in SHR while exercise
      training offset this process. Exercise training was the main factor influencing
      the improvement of intramyocardial arteries length density and significantly
      reduced the aortic wall thickness and increased the density of smooth muscle cell
      nuclei per tunica media unit area. CONCLUSIONS: In ovariectomized SHR, exercise
      training exerts beneficial effects diminishing adverse cardiac and aortic wall
      remodeling, mainly by reducing interstitial myocardial fibrosis, improving
      myocardial vascularization, and sustaining the number of cardiomyocytes.

PMID- 16607104
TI  - Serum cholesterol efflux potential in postmenopausal women treated with isolated
      isoflavones.
AB  - OBJECTIVE: Based on the low cardiovascular risk in Asian populations,
      phytoestrogens are believed to provide vascular benefits. To elucidate the
      mechanisms behind the possible cardiovascular effects of phytoestrogens, we
      evaluated reverse cholesterol transport by assessing the capacity of serum to
      promote cholesterol efflux in postmenopausal women treated with isolated
      isoflavones. DESIGN: Thirty postmenopausal women were treated in a randomized,
      placebo-controlled, crossover trial with isoflavones or placebo for 3 months
      interrupted by a 2-month washout period. Serum samples were collected before and
      after each treatment period, and the cholesterol efflux potential was
      investigated by using H-cholesterol--labeled Fu5AH cells in culture. RESULTS:
      Serum promoted 20.2% +/- 3.0% and 19.9% +/- 3.4% (mean +/- SD) cholesterol efflux
      after isoflavonoid treatment and after placebo treatment, respectively. Thus, the
      isoflavone treatment did not affect serum cholesterol efflux. We also studied
      separately women who produced high concentrations of the isoflavone metabolite
      equol into serum because some studies suggest that equol could exert favorable
      vascular effects. However, there was no difference in serum cholesterol efflux
      capacity between the equol producers (n = 15) and non-equol producers (n = 15).
      CONCLUSIONS: In conclusion, isoflavone treatment did not affect serum cholesterol
      efflux potential in postmenopausal women. Based on our findings, isolated
      isoflavones do not provide vascular benefits by improving cholesterol efflux.

PMID- 16607105
TI  - Diet, activity, and other lifestyle risk factors for forearm fracture in
      postmenopausal women in China: a case-control study.
AB  - OBJECTIVE: Forearm fractures are a major cause of disability in postmenopausal
      women, but the risk factors have not been previously studied in China and the
      results from Western studies may not be applicable to the Chinese population. The
      aim of this study was to determine whether calcium intake, activity level,
      lifestyle, and other factors are associated with risk of forearm fracture among
      Chinese postmenopausal women. DESIGN: In this case-control study, the authors
      used a structured questionnaire to assess potential risk factors in 209
      postmenopausal women 50 to 70 years old with new forearm fractures identified in
      eight hospitals in Chengdu and in age and location of residence-matched control
      subjects randomly selected from the community. RESULTS: Adjusted odds ratios (95%
      CIs) were as follows: each quintile increase in current energy intake 0.46 (0.36,
      0.60); fifth quintile energy-adjusted current calcium intake versus lowest
      quintile, 0.17 (0.06, 0.47); eating bean products when 30 to 49 years old, 0.15
      (0.05, 0.47); eating meat, 0.13 (0.02, 0.74) and eating pork ribs, 0.37 (0.17,
      0.83) when 16 to 29 years old; greater past activity, 0.78 (0.68, 0.89) and
      present activity, 0.84 (0.74-0.96); greater height (per centimeter), 1.12 (1.06,
      1.20); each year irregular menses before menopause, 1.25 (1.04, 1.49); each floor
      of residence, 1.71 (1.38, 2.12); and prior fracture in first- or second-degree
      relatives, 2.74 (1.08, 6.92). CONCLUSION: Some risk factors for forearm fractures
      were similar to those described in white women, whereas others were specific to
      this ethnic setting, and would need to be considered in future preventive
      programs.

PMID- 16607106
TI  - Recent reversal of trends in hormone therapy use in a European population.
AB  - OBJECTIVE: The impact of the Women's Health Initiative (WHI) randomized trial
      results published in July 2002 indicating that hormone therapy (HT) is
      potentially harmful for the heart and the mammary gland of naturally
      postmenopausal women was assessed for the first time in a European population.
      DESIGN: This study continuously monitored HT use from 1994 through 2003 in a
      population-based random sample of 5,758 women aged 35 to 74 years residing in
      Geneva (city and canton), Switzerland, yielding 1,938 naturally postmenopausal
      women with an intact uterus and 206 artificially postmenopausal women. Women in
      the former subgroup weighed substantially less than their WHI trial counterparts
      but were not otherwise at lower risk for cardiovascular disease. RESULTS: Among
      the naturally postmenopausal women with an intact uterus, current HT use
      increased from 29% to 46% (P < 0.0001) through July 2002 and then decreased
      abruptly to 31% in 2003. Current HT use remained stable (range, 38%-46%; trend P
      = 0.92) among the artificially postmenopausal women. CONCLUSIONS: Successive
      annual increases from 1994 through 2001 in the prevalence of current HT use by
      postmenopausal women living in Geneva were dramatically reversed to the level in
      1994 just after the results of the WHI trial were published, but only for
      naturally postmenopausal women with an intact uterus. Approximately one in three
      of the latter women who stopped using HT may also have lost its beneficial
      effects on bone health.

PMID- 16607107
TI  - Age at natural menopause and factors associated with menopause state among Puerto
      Rican women aged 40-59 years, living in Puerto Rico.
AB  - OBJECTIVE: The timing of menopause is associated with multiple health outcomes in
      female populations including all-cause mortality, heart disease, breast cancer,
      and osteoporosis. Although research suggests that age at menopause varies in
      different ethnic groups, data on age at menopause among Hispanic women are
      limited. DESIGN: The present cross-sectional study estimates age at natural
      menopause among a sample of 1,272 Puerto Rican women aged 40 to 59 years who
      participated in health fairs held in 22 municipalities of Puerto Rico between May
      2000 and November 2001. Cox proportional hazard regression analysis was used to
      characterize age at natural menopause and its association with relevant
      covariates. RESULTS: The overall adjusted median age at natural menopause was
      51.3 years. Current employment (hazard ratio = 0.75, 95% CI: 0.59-0.95) and
      parity of two or three children as compared with having no children or one child
      (hazard ratio = 0.73, 95% CI: 0.54-0.98) were associated with a later menopause.
      CONCLUSIONS: This study provides a robust estimate of age at menopause for Puerto
      Rican women, which is similar to overall estimates previously reported for US
      populations, but higher than estimates for other Hispanic populations. Our
      results confirm attributes associated with age at menopause and provide
      information relevant to understanding the potential chronic disease burden of
      Puerto Rican women as they age.

PMID- 16607108
TI  - Attitudes of Korean clinicians to postmenopausal hormone therapy after the
      Women's Health Initiative study.
AB  - OBJECTIVE: To assess the attitudes of Korean physicians toward hormone therapy
      (HT) after publication of the Women's Health Initiative (WHI) study. DESIGN: Self
      administered questionnaires, consisting of 22 items, were sent by mail to the
      members of the Korean Society of Menopause. RESULTS: More than 95% of Korean
      physicians were aware of the WHI study. The HT prescription rate decreased by 16%
      after publication of the WHI report; approximately half of the physicians who
      continued prescribing HT changed their prescriptions. The largest decreases
      occurred in regimens using conjugated equine estrogens and medroxyprogesterone
      acetate, for which prescriptions of sequential and continuous-combined regimens
      decreased by 20.7% and 22.7%, respectively. In contrast, the prescription rate
      for tibolone increased by 3.6%. Approximately 30% of physicians changed from
      standard to low doses, and 67.8% shortened the duration of HT. After publication
      of the WHI report, the main reasons for not prescribing or discontinuing HT were
      patient refusal and increased risk of cardiovascular disease, rather than breast
      cancer risk. After publication of the WHI report, the number of physicians who
      prescribed alternative or complementary medicines increased, the rate of HT
      prescription for the prevention of osteoporosis decreased, and the number of
      postmenopausal outpatients decreased. CONCLUSIONS: Despite the results of the WHI
      report, most Korean physicians who participated in this study continued
      prescribing HT; however, approximately half of those who continued prescribing HT
      changed their prescriptions. The greatest change occurred in regimens using
      conjugated equine estrogens and medroxyprogesterone acetate.

PMID- 16607109
TI  - Effects of ultralow-dose transdermal estradiol on postmenopausal symptoms in
      women aged 60 to 80 years.
AB  - OBJECTIVE: To investigate the effect of ultralow-dose transdermal estradiol on
      postmenopausal symptoms and side effects in a cohort of largely asymptomatic
      postmenopausal women aged 60 to 80 years. DESIGN: This secondary analysis used
      data from the UltraLow-dose Transdermal estRogen Assessment trial, a randomized,
      placebo-controlled, double-blind trial in postmenopausal women to determine the
      skeletal effects and safety of ultralow-dose transdermal estradiol. Four hundred
      seventeen postmenopausal women, aged 60 to 80 years, were randomly assigned to
      receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo
      (n = 209). Participants were queried at each clinic visit about postmenopausal
      symptoms and side effects purported to be associated with estrogen therapy using
      a standardized questionnaire. RESULTS: At baseline, 16% of women reported hot
      flashes, 32% reported vaginal dryness, and 35% reported trouble sleeping. Women
      who received ultralow-dose estradiol were no more likely to report improvement of
      hot flashes, vaginal dryness, or sleep difficulties than those who received
      placebo. Treatment with ultralow-dose estradiol did not cause breast tenderness,
      uterine bleeding, or other symptoms often attributed to estrogen, but vaginal
      discharge was more common in women who received estradiol compared with those who
      received placebo. CONCLUSION: In this population of older, largely asymptomatic
      women, ultralow-dose transdermal estradiol did not improve postmenopausal
      symptoms and did not cause side effects other than vaginal discharge. Further
      study is needed to determine whether this dose of transdermal estradiol is
      effective in treating symptoms of postmenopause in younger, more symptomatic
      women.

PMID- 16607110
TI  - Postmenopausal hormone therapy: new questions and the case for new clinical
      trials.
AB  - Observational studies suggest that postmenopausal hormone therapy (HT) prevents
      coronary heart disease, whereas randomized clinical trials have not confirmed a
      cardioprotective effect. Although observational studies may have overestimated
      the coronary benefit conferred by postmenopausal hormone use, there are other
      plausible explanations for the apparent discrepancy between previous results and
      the less favorable findings from clinical trials such as the large Women's Health
      Initiative. There is now a critical mass of data to support the hypothesis that
      age or time since menopause may importantly influence the benefit-risk ratio
      associated with HT, especially with respect to cardiovascular outcomes, and that
      the method of administration, dose, and formulation of exogenous hormones may
      also be relevant. Although the weight of the evidence indicates that older women
      and those with subclinical or overt coronary heart disease should not take HT,
      estrogen remains the most effective treatment currently available for vasomotor
      symptoms, and its effects on the development of coronary disease in newly
      postmenopausal women remain unclear. Moreover, effects of HT on quality of life
      and cognitive function in recently postmenopausal women merit further study.
      These unresolved clinical issues provide the rationale for the design of the
      Kronos Early Estrogen Prevention Study, a 5-year randomized trial that will
      evaluate the effectiveness of low-dose oral estrogen and transdermal estradiol in
      preventing progression of atherosclerosis in recently postmenopausal women.

PMID- 16607111
TI  - Low-dose estrogen therapy for prevention of osteoporosis: working our way back to
      monotherapy.
AB  - The risks of low bone mineral density, osteoporosis and fractures, are major
      concerns in postmenopausal women. Although postmenopausal hormone therapy is
      effective for reducing these risks, safety issues have been raised by the results
      of studies such as the Women's Health Initiative. Although there are
      scientifically valid reasons to be wary of the general applicability of the
      Women's Health Initiative findings, the study has underscored the continuing need
      for research into new forms of menopausal hormone therapy. Low-dose transdermal
      estrogen monotherapy can preserve bone density while relieving vasomotor
      symptoms. Transdermal administration may offer advantages, including lack of
      first-pass liver metabolism, which permits the use of lower doses and avoids a
      negative impact on the lipid profile. Moreover, a recently published 2-year study
      of ultra-low-dose transdermal estrogen monotherapy in an older population similar
      to that of the WHI reported significant increases in bone mineral density,
      accompanied by significant reductions in markers of bone turnover, with no
      increased risk of endometrial hyperplasia or other side effects. Additional
      studies are warranted to shed further light on the possible benefits of low-dose
      estrogen monotherapy for the prevention of bone loss in postmenopausal women.

PMID- 16607112
TI  - Monitoring reproductive aging in a 5-year prospective study: aggregate and
      individual changes in steroid hormones and menstrual cycle lengths with age.

PMID- 16607114
TI  - Nutritive blood flow as an essential element supporting muscle anabolism.
AB  - PURPOSE OF REVIEW: Much of the recent literature concerning hormonal effects on
      muscle assumes that full perfusion occurs at all times such that nutrient and
      hormone delivery is complete. New methods to measure the extent of nutritive
      blood flow in muscle show that this is not the case and that anabolic hormones
      such as insulin increase nutritive flow and that other agents that increase bulk
      flow have little effect. This review examines the latest developments concerning
      insulin action to increase nutritive perfusion of muscle and agents that interact
      with this effect and which could potentially modulate anabolism. RECENT FINDINGS:
      We examine recent attempts to define the anatomical nature of non-nutritive flow
      route in muscle, the quick onset of insulin action to recruit nutritive blood
      flow at doses lower than that which activates glucose uptake and bulk blood flow,
      actions of the inflammatory cytokine tumour necrosis factor alpha TNFalpha to
      oppose physiologic insulin action, interfibrillar fat depots that grow on the non
      nutritive vasculature of muscle and underpin a 'vascrine hypothesis', and drugs
      that reduce insulin resistance by ameliorating vascular dysfunction. SUMMARY:
      Recognition that nutrient and hormone delivery to muscle is controlled by
      microvascular perfusion and not necessarily by bulk blood flow is the key issue.

PMID- 16607115
TI  - Redox regulation in anabolic and catabolic processes.
AB  - PURPOSE OF REVIEW: Muscle wasting as it typically occurs in old age and in
      certain diseases is poorly understood. This review summarizes recent findings
      suggesting a role for redox-sensitive signaling cascades in catabolic processes.
      RECENT FINDINGS: The redox-sensitive transcription factors nuclear factor kappaB
      and activator protein 1 facilitate ubiquitin-proteasome-dependent proteolysis.
      Nuclear factor kappaB also plays a role in induced expression of tumor necrosis
      factor alpha and other inflammatory cytokines that have been implicated in
      catabolic processes. The activities of nuclear factor kappaB and activator
      protein 1 are stimulated not only by hydrogen peroxide, which is produced in
      tissues by regulated enzymatic processes, but also by an oxidative shift in thiol
      disulfide redox status. The oxidative shift that is typically seen in old age and
      certain catabolic conditions may thus play a causative role in catabolic
      processes. Another prominent case in point is insulin-independent 'basal' insulin
      receptor kinase activity, which is strongly enhanced by hydrogen peroxide or by
      an oxidative shift in redox status. The insulin receptor signaling cascade
      induces anabolic and anticatabolic effects, but its abnormal upregulation under
      starving conditions potentially compromises glucose and amino acid homeostasis.
      In genetic animal studies, impairment of insulin receptor signaling was shown to
      increase life span. SUMMARY: These findings may provide a rationale for cysteine
      supplementation in catabolic conditions.

PMID- 16607116
TI  - Anticatabolic properties of melanocortin-4 receptor antagonists.
AB  - PURPOSE OF REVIEW: Health problems related to weight regulation are increasingly
      common in the USA and around the world. Although obesity and associated
      complications garner the most attention in the media, clinical problems at the
      opposite end of the spectrum, such as involuntary disease-associated weight loss
      or cachexia, are equally devastating. This review focuses on the role of the
      central melanocortin system in body weight regulation, and specifically on the
      anticatabolic properties of antagonists of the melanocortin-4 receptor. RECENT
      FINDINGS: Over the past several years, the central melanocortin system has
      emerged as a major contributor to the body weight regulatory system in both
      animals and humans. In particular, the melanocortin-4 receptor, its endogenous
      agonist alpha-melanocyte stimulating hormone, and its endogenous antagonist
      agouti-related protein have been shown to be vital to the maintenance of normal
      body weight in both genetic and physiologic experiments. This system is now the
      target of multiple drug discovery endeavors, as the search continues for
      effective treatments for both obesity and cachexia. Several investigators have
      recently shown that selective synthetic antagonists of the melanocortin-4
      receptor can prevent or attenuate the development of cachexia in animal models of
      acute and chronic disease. SUMMARY: An understanding of the biology of weight
      regulation, including both appetite regulation and energy metabolism, is vital if
      we are to unravel the etiology of and develop effective treatment for obesity and
      cachexia. The data reviewed here supporting a role for melanocortin-4 receptor
      antagonists in the treatment of catabolism represent an important advance in this
      field.

PMID- 16607117
TI  - Glutamine: the first clinically relevant pharmacological regulator of heat shock
      protein expression?
AB  - PURPOSE OF REVIEW: It is well known that enhanced heat shock protein expression
      protects organisms against morbidity and mortality following experimental
      injury/illness. Presently, chemical/gene therapy based laboratory methods of
      enhancing heat shock protein expression are impractical for clinical application.
      Our laboratory has shown glutamine enhances heat shock protein expression
      following models of experimental illness/injury. The purpose of this review is to
      examine recent data supporting the use of glutamine as a clinically relevant
      enhancer of heat shock protein expression. RECENT FINDINGS: Recent studies
      indicate glutamine induces heat shock protein-70, HO-1 (heat shock protein-32),
      and heat shock protein-27 in models of illness/injury. Enhanced expression of
      heat shock proteins correlates with improved outcome in these models. Further, in
      vitro data reveal glutamine enhances DNA binding of heat shock factor-1 (heat
      shock protein transcription factor) to its promoter. Finally, recently published
      pilot data show that glutamine enhances serum heat shock protein-70 expression in
      critically ill patients and this enhanced expression correlates with improved
      outcome. SUMMARY: Currently, extensive data support glutamine as a gene level
      regulator of heat shock protein expression. Glutamine depletion, following
      critical illness/injury, is likely to lead to a state in which organisms are
      unable to induce heat shock proteins appropriately. Further, pharmacologic
      supplementation of glutamine potentiates the heat shock protein response prior to
      and following a stress. Pharmacologic trials utilizing glutamine to enhance heat
      shock proteins in humans are indicated.

PMID- 16607118
TI  - Gene therapy with anabolic growth factors to prevent muscle atrophy.
AB  - PURPOSE OF REVIEW: Many situations cause muscle atrophy. When severe, muscle
      atrophy is associated with an increase in morbidity and mortality. This loss of
      muscle mass is thought to be due to an imbalance between catabolic and anabolic
      pathways, resulting in an increase of muscle protein proteolysis and in a
      decrease in protein synthesis. Changes in muscle levels of muscle growth factors
      are thought to play a major role in this imbalance. Despite recent better
      understanding of the metabolic and molecular derangements leading to muscle
      wasting, therapy of muscle atrophy still has a poor success rate. RECENT
      FINDINGS: The recent demonstration that changes in local growth factors, such as
      insulin-like growth factor-I and myostatin, occur during muscle atrophy has
      stimulated research interest to prevent muscle mass loss by delivering these
      growth factors or their inhibitors into the muscle. During the last few years,
      several advances in the field of muscle gene transfer, using electroporation or
      recombinant adeno-associated viral vectors, have opened novel therapeutic ways to
      deliver growth factors able to counteract the loss of muscle mass. SUMMARY:
      Preventing decrease of insulin-like growth factor-I muscle, or inhibiting
      myostatin action by local genes over-expression, may provide a clinically
      relevant avenue for the preservation, attenuation or reversal of disease-related
      muscle loss.

PMID- 16607119
TI  - Anabolic potential and regulation of the skeletal muscle satellite cell
      populations.
AB  - PURPOSE OF REVIEW: Satellite cells are required for muscle regeneration to occur
      properly. An understanding of the mechanisms that increase their number is
      important for potential therapeutic use in a variety of muscle disorders. RECENT
      FINDINGS: This article reviews the state of knowledge regarding mechanisms and
      factors involved in regulating the satellite cell population. An overview of the
      soluble factors intrinsic to the regulation of the activation, proliferation and
      differentiation of satellite cells is presented. We also highlight our current
      knowledge of satellite cell specification that provides a potential basis for
      increasing satellite cell numbers by manipulating different cell types. Finally,
      summarizing our current knowledge of satellite cell self-renewal offers insight
      for possible avenues to increase the supply of satellite cells. SUMMARY: Multiple
      approaches for increasing the number and activity of satellite cells will lead to
      treatments for muscular diseases. For example, in muscular dystrophy the
      exhaustion of satellite cells is the principal cause of death.

PMID- 16607121
TI  - Antimicrobial effects of arginine and nitrogen oxides and their potential role in
      sepsis.

PMID- 16607122
TI  - Practicalities of selenium supplementation in critically ill patients.
AB  - PURPOSE OF REVIEW: To review the reason for and clinical effects of selenium
      supplementation in critically ill patients. RECENT FINDINGS: Selenium-dependent
      enzymes and selenoprotein P regulate immune and endothelial cell function.
      Obviously not the anorganic compounds of selenium but the activity of selenium
      dependent enzymes is the most important factor modulating the immune system and
      the clinical outcome of patients. Despite low selenium levels in severely ill
      patients and low glutathione peroxidase activity associated with the extent of
      multiorgan dysfunction, only a few trials have investigated the effect of
      selenium supplementation on clinical outcome. A metaanalysis did not reveal a
      statistically significant survival rate with selenium supplementation, but
      suggested a dose-dependent trend. The recently completed multicentre trial on
      high-dose selenium supplementation in septic patients also did not reveal a
      significant overall reduction in mortality. SUMMARY: The available evidence
      suggests that selenoproteins play an important role in the immunomodulation of
      critically ill patients and a sodium selenite supplementation upregulates these
      selenoenzymes. The intervention trials with sodium selenite performed to date are
      small and therefore only a tendency in reduction of morbidity and mortality could
      be demonstrated. Larger trials are necessary to show the supposed benefits and
      risks of selenite supplementation in critically ill patients.

PMID- 16607120
TI  - Angiotensin II as candidate of cardiac cachexia.
AB  - PURPOSE OF REVIEW: Congestive heart failure is increasing in prevalence and
      represents a major public health problem. The syndrome of advanced heart failure
      often includes muscle wasting, commonly termed cardiac cachexia, which is a
      predictor of poor outcome. Mechanisms of cardiac cachexia are poorly understood,
      but there is recent evidence that increased angiotensin II, interacting with the
      insulin-like growth factor-1 system, plays an important role. RECENT FINDINGS: In
      animals, angiotensin II produces weight loss through a pressor-independent
      mechanism, accompanied by decreased levels of circulating and skeletal muscle
      insulin-like growth factor-1 and increased mRNA levels of the ubiquitin ligases
      atrogin-1 and Muscle RING finger-1 in skeletal muscle. Reduced insulin-like
      growth factor-1 action in muscle leads to increased proteolysis, through the
      ubiquitin-proteasome pathway, and increased apoptosis. These changes are blocked
      by muscle-specific expression of insulin-like growth factor-1, likely to be via
      the Akt/mTOR/p70S6K signaling pathway. SUMMARY: The link between insulin-like
      growth factor-1, the ubiquitin-proteasome pathway, and angiotensin II effects has
      widespread clinical implications for the understanding of mechanisms of catabolic
      conditions. Therapeutic interventions targeting cross-talk mechanisms between
      angiotensin II and insulin-like growth factor-1 effects could provide new
      approaches for the treatment of muscle wasting.

PMID- 16607123
TI  - Recent developments in aluminium contamination of products used in parenteral
      nutrition.
AB  - PURPOSE OF REVIEW: This review evaluates recent developments concerning aluminium
      contamination of products used in the preparation of parenteral nutrition
      solutions and the failure of the pharmaceutical industry to respond to these
      concerns. The difficulty in meeting the intent of the recent US Food and Drug
      Administration mandate to reduce aluminium exposure with currently available
      parenteral nutrition additives is addressed. This review also summarizes the
      issues associated with aluminium toxicity, the patient populations at risk,
      treatment options, and compounding considerations. RECENT FINDINGS:
      Unfortunately, the published literature detailing the toxicities seen from
      aluminium exposure in the parenteral nutrition patient are primarily limited to
      those published in the 1980s and 1990s. Recent publications refer back to these
      classic papers and discuss the challenges that practitioners face when trying to
      apply the recommendations of the recently implemented Food and Drug
      Administration mandate with outdated literature. Few studies have been published
      to validate those earlier findings. SUMMARY: The issues surrounding aluminium
      toxicity are real and must be addressed. In order to make meaningful changes in
      clinical practice, low aluminium parenteral nutrition additives are needed and
      studies must be conducted using currently available products. It remains a
      challenge to optimize nutritional intake from parenteral nutrition and at the
      same time reduce aluminium exposure.

PMID- 16607124
TI  - Indirect calorimetry: methodology, instruments and clinical application.
AB  - PURPOSE OF REVIEW: This review aims to identify the basic methods for accurately
      measuring a patient's energy expenditure in clinical nutrition practice by
      indirect calorimetry, and the impact upon a disease state of applying the results
      obtained. RECENT FINDINGS: The open-circuit method is the most widely used in the
      majority of classical instruments for measuring energy consumption. Advances in
      gas exchange measurement have made this technique readily and precisely available
      at the bedside. Nevertheless, it is important to understand its intricate primary
      methodology for safe and correct application. The stress and activity factors
      should be carefully and specifically applied, and the respiratory quotient
      abandoned, for tailoring a patient's daily nutrition regimens. Caloric
      expenditure measured by indirect calorimetry coupled with the doubly labeled
      water technique introduced the concept of physical activity energy expenditure,
      which added to resting energy expenditure results in total daily energy
      expenditure. Compact modular and handheld devices have been introduced into the
      market, together with similar technology for evaluating exercise energy
      expenditure, making utilization easier, safer and precise. In the critically ill
      population, which is exposed to medical and surgical interventions, indirect
      calorimetry has greatly changed the practice of caloric administration,
      significantly reducing the total daily amount. SUMMARY: In conclusion, one has to
      be careful when choosing devices, and understanding and clinically applying the
      results obtained by indirect calorimetry, bearing in mind that measured resting
      energy expenditure should be the daily caloric goal in order to diminish clinical
      morbidity.

PMID- 16607125
TI  - Evaluation of intestinal trophism: review of current methods and techniques.
AB  - PURPOSE OF REVIEW: This review aims to cover the methods and techniques currently
      used by researchers to evaluate intestinal trophism. RECENT FINDINGS: Although
      subjected to criticisms, conventional gut trophism evaluation by both
      morphological and histological parameters continues to be largely reported. The
      metaphase arrest technique and the detection of H-tymidine have been used less
      frequently in recent years due to increasing interest in the immunohistochemical
      methods such as 5-bromo-2'deoxy-uridine, Ki-67, and proliferating cell nuclear
      antigen. Along with common techniques for the evaluation of intestinal trophism,
      the combination of methods that includes a measurement of cell proliferation and
      an apoptotic index in the same study are most valuable and are increasing in the
      current literature. SUMMARY: Evaluation of intestinal trophism is an important
      issue for both clinical and experimental nutritional studies. The
      immunohistochemical techniques are the gold standard to access cell
      proliferation. Evaluation of proliferation and apoptosis at the same time may
      offer a more reliable evaluation of the actual status of gut trophism.

PMID- 16607126
TI  - Indications and limitations of the use of subjective global assessment in
      clinical practice: an update.
AB  - PURPOSE OF REVIEW: Subjective global assessment is a clinical tool for assessing
      nutritional status that merges alterations in body composition and physiological
      function. Although it was first described almost two decades ago, many studies
      using this method have been published during the past few years. This review
      describes recent findings from such studies. RECENT FINDINGS: Subjective global
      assessment has proved to be a good nutritional assessment and prognostic
      indicator in several clinical situations. Agreement between subjective global
      assessment and newer screening methods is not always acceptable, and it has not
      been validated with respect to clinical outcome. Some modifications have been
      suggested that may increase the sensitivity of subjective global assessment as a
      screening tool. A scored version of subjective global assessment for cancer
      patients is now being validated for use in other patient groups. This could
      increase its utility in nutritional intervention studies if it can be
      demonstrated that subtle changes in nutritional status are reflected by numerical
      scores in patient-generated subjective global assessment. SUMMARY: Subjective
      global assessment represents a good option for assessing nutritional status in
      various clinical situations. As a screening tool, it better identifies
      established malnutrition than nutritional risk but its sensitivity is suboptimal.
      The scored version of subjective global assessment may have advantages and extend
      the usefulness of this tool even further.

PMID- 16607127
TI  - Organization of managed clinical networking for home parenteral nutrition.
AB  - PURPOSE OF REVIEW: Home parenteral nutrition (HPN) is an established treatment
      for intestinal failure, and organization of HPN is variable throughout the UK and
      Europe. Managed clinical networking is the single most important feature of the
      UK National Health Service strategy for acute services in Scotland and has the
      potential to improve the management of HPN patients. This review addresses the
      role of managed clinical networking in HPN and compares outcome data between
      centres. RECENT FINDINGS: The Scottish HPN Managed Clinical Network has published
      the main body of the current literature supporting the concept of managed
      clinical networking in this context. The Network is responsible for the
      organization and quality assurance of HPN provision in Scotland, and has been
      established for 5 years. It has captured significant patient data for the purpose
      of clinical audit and illustrates that this is an effective model for the
      management of this patient population. SUMMARY: This review provides advice for
      other areas wishing to improve equity of access, and to smooth the patient
      journey between primary, secondary and tertiary health care in the context of
      artificial nutrition support.

PMID- 16607129
TI  - Experimental evidence for early nutritional programming of later health in
      animals.
AB  - PURPOSE OF REVIEW: The developmental origins of adult disease represent a
      burgeoning area of research for which it has been suggested that up to 50% of the
      current incidence of later adult disease may be explained or even alleviated.
      Therefore, it is not surprising that there has been a substantial increase in the
      number of publications on this subject. In this review, some of the most
      important recent publications will be highlighted, particularly those focusing on
      the consequences for later cardiovascular control and obesity. RECENT FINDINGS:
      The review will consider the extent to which both increased and decreased
      maternal nutrient intake in relevant animal models can result in offspring that
      are at greater risk of later disease, and will indicate the potential mechanisms
      involved. Particular focus will be given to effects on glucocorticoids, potential
      epigenetic effects, and the extent to which male or female offspring may be
      differentially programmed. In addition, the potential for nutritional or
      endocrine interventions during lactation in order to overcome these adverse
      outcomes will be covered. SUMMARY: Inappropriate growth during pregnancy,
      lactation and/or childhood can result in individuals whose risk of later
      cardiovascular disease is greatly increased. By considering the critical
      importance of the maternal diet from before conception through to lactation,
      there is a clear potential to substantially improve the health of all children
      and adults.

PMID- 16607130
TI  - Diet of lactating women and allergic reactions in their infants.
AB  - PURPOSE OF REVIEW: To evaluate whether the diet of lactating women modulates the
      development of allergic disease in their children. RECENT FINDINGS: Although
      maternal avoidance of common food protein allergens was previously recommended
      for lactating women with infants predisposed to allergic disease, recent expert
      reviews have concluded that there is no strong evidence to support this position.
      A recent well-controlled study, using egg as an allergen, confirmed that the
      appearance of food proteins in human milk is common, but this can be highly
      variable between women even after consuming the same challenge (dose) food. On
      the other hand, preliminary data suggest that increasing dietary n-3 fatty acids
      may offer protection from the development of some childhood allergies. A recent
      animal study offers mechanistic support, indicating that perinatal diets high in
      n-3 fatty acids can induce oral neonatal tolerance more effectively compared with
      diets predominating in n-6 fatty acids. SUMMARY: Current data do not support the
      use of maternal antigen-avoidance diets during lactation as a strategy to prevent
      childhood allergies. Controlled trials are required to evaluate the efficacy of
      maternal dietary n-3 fatty acid interventions in preventing allergic disease in
      at-risk infants.

PMID- 16607131
TI  - Breast feeding and future health.
AB  - PURPOSE OF REVIEW: This review discusses the long-term health effects of breast
      feeding, based on the most relevant publications from the second half of 2004 and
      2005. RECENT FINDINGS: The positive effect of breast feeding on later cognitive
      function continues to be the most consistent and important effect. Also, breast
      feeding is likely to protect against some immune-related diseases later in life,
      such as type 1 diabetes, coeliac disease, inflammatory bowel diseases and perhaps
      cancer. The evidence for an effect on allergic disease continues to be
      inconclusive. Furthermore, breast feeding seems to be associated with a lower
      blood pressure and serum cholesterol, but there is no clear association with
      cardiovascular disease or death. Most new studies and meta-analyses show a
      protective effect against later obesity, but this seems to be small. A new
      hypothesis suggests that breast feeding programmes the insulin-like growth factor
      axis and results in higher growth velocity later in childhood. SUMMARY: Evidence
      is increasing that breast feeding, beyond its well-established beneficial effects
      during the breast-feeding period, also confers long-term benefits. These effects
      are not strong at the individual level, but are likely to be of importance at the
      population level. Since the majority of the studies are observational, however,
      it is difficult to prove causality.

PMID- 16607132
TI  - Causes and consequences of inadequate substrate supply to pediatric ICU patients.
AB  - PURPOSE OF REVIEW: The prevalence of malnutrition among children admitted to a
      pediatric intensive care unit is still high. Assessment of nutrient supply is
      essential in the care of critically ill children because inadequate nutrition can
      increase morbidity and mortality. This review covers the causes and consequences
      of inadequate nutrient supply to critically ill children. RECENT FINDINGS: A
      major factor contributing to the cause of inadequate nutrient supply is the
      difficulty in estimating nutritional needs of the individual child. Reasonable
      values for energy expenditure can be derived from prediction formulae but
      measuring energy expenditure by indirect calorimetry is useful in selected cases.
      Furthermore, under-prescription and inadequate delivery of nutrients caused by
      fluid volume restriction, procedural interruptions or cessation because of
      gastrointestinal intolerance or mechanical problems cause additional nutritional
      deficits. As routine nutritional assessment is lacking in many pediatric
      intensive care units, the ability to monitor the adequacy of nutritional support
      is poor. SUMMARY: In the majority of children admitted to a pediatric intensive
      care unit, nutritional problems--both underfeeding and overfeeding--occur during
      admission due to poor estimation of nutritional needs, under-prescribing and
      problems in the delivery of the nutrients. Recommendations are made in order to
      prevent inadequate nutritional supply and its potentially harmful consequences in
      critically ill children.

PMID- 16607133
TI  - Short bowel syndrome and intestinal transplantation in children.
AB  - PURPOSE OF REVIEW: This review summarizes recent knowledge and clinical practice
      for pediatric patients suffering extensive intestinal resection causing short
      bowel syndrome. This condition requires the use of parenteral nutrition, as long
      as intestinal failure persists, and may be, in some selected cases, an indication
      for intestinal transplantation. RECENT FINDINGS: Biological evaluation of
      intestinal failure is becoming possible with the use of plasma citrulline as a
      marker of intestinal mass. Few epidemiological data are available; some indicate
      an increased incidence of short bowel syndrome-related gastroschisis and
      persistent high incidence of necrotizing enterocolitis. Morbidity and mortality
      data in pediatric patients with short bowel syndrome are limited, while long-term
      outcome is better documented from recently reported cohorts. Non-transplant
      surgery is one of the best options for patients with unadapted short bowel
      syndrome. Isolated liver transplantation may be avoided. The use of trophic
      factors for enhancing mucosal hyperplasia still remains disappointing. SUMMARY:
      The management should include therapies adapted to each stage of intestinal
      failure, based on a multidisciplinary approach in centers involving pediatric
      surgery, pediatric gastroenterology, parenteral nutrition expertise, home
      parenteral nutrition program, and liver-intestinal transplantation experience. If
      managed appropriately, the prognosis of short bowel syndrome is excellent, with
      limited indications for intestinal and/or liver transplantation. Timing for
      patient referral in specialized centers remains an issue.

PMID- 16607134
TI  - Enteral feeding in inflammatory bowel disease.
AB  - PURPOSE OF REVIEW: Treatment algorithms for inflammatory bowel disease are
      changing rapidly. Increased and earlier use of immunomodulatory drugs and
      availability of biologic agents have reduced dependence on corticosteroids and
      made mucosal healing a realistic goal. It is timely to debate the role of enteral
      nutrition in this evolving therapeutic armamentarium for Crohn's disease, and to
      examine the mechanisms of its anti-inflammatory effects in light of current
      understanding of disease pathogenesis. RECENT FINDINGS: Clinical studies have
      suggested that response to enteral nutrition is associated with decreased mucosal
      inflammation in Crohn's disease, that isolated Crohn's colitis is less responsive
      and that exclusive enteral nutrition is required. Basic research has demonstrated
      that lipids in the intestinal lumen can alter signalling of the mucosal immune
      system by intestinal epithelial cells. Exclusive enteral nutrition is associated
      with alteration of enteric microflora. SUMMARY: Enteral nutrition is an
      efficacious treatment of active inflammation involving the ileum; recent-onset
      disease may be particularly responsive. The significance of effects on enteric
      flora deserves further exploration in view of the importance of microbes to
      disease pathogenesis.

PMID- 16607135
TI  - Parenteral lipid emulsions in paediatrics.
AB  - PURPOSE OF REVIEW: Lipid emulsions are crucial for providing essential fatty
      acids and energy in infants and children requiring parenteral nutrition. There is
      ongoing debate about the optimal composition of lipid emulsions and the optimal
      timing for introducing lipids to the parenteral nutrition of premature infants in
      order to enhance the benefits and to minimize the risk of complications. RECENT
      FINDINGS: Several studies have investigated the effects of early compared with
      late administration of lipid emulsions. A meta-analysis demonstrated that early
      introduction of lipid emulsions does not improve short-term growth or prevent
      morbidity and mortality in preterm infants. On the other hand, early introduction
      of lipid emulsions was not shown to increase the risk of complications. A number
      of studies have investigated the effects of different fatty acid compositions in
      lipid emulsions on peroxidation. In-vitro findings suggest that lipid
      peroxidation is related to the polyunsaturated fatty acid content and inversely
      related to the alpha-tocopherol/polyunsaturated fatty acid ratio of the fat
      emulsion. The composition of lipid emulsions has also been shown to influence
      fatty acid metabolism. A mixture of medium-chain and long-chain triglycerides
      seems to enhance the incorporation of essential fatty acids and long-chain
      polyunsaturated fatty acids into circulating lipids when compared with an
      emulsion containing only long-chain triglycerides. SUMMARY: Although the
      composition of lipid emulsions has been demonstrated to influence peroxidation
      and fatty acid metabolism, outcome studies are needed to confirm advantageous
      effects.

PMID- 16607136
TI  - Current world literature. Anabolic and catabolic signals.

PMID- 16607138
TI  - Identification of risk factors for stone recurrence after endoscopic treatment of
      bile duct stones.
AB  - Recurrence of bile duct stones after endoscopic stone removal has been reported
      ranging from 4 to 24%. The risk of late complications such as stone recurrence is
      an important issue, especially for relatively young, otherwise healthy, patients
      with many years of future exposure time. The risk factors true recurrence of bile
      duct stones after endoscopic sphincterotomy (EST) and stone clearance are
      suboptimally defined. If patients at significant risk for stone recurrence could
      be identified, closer follow-up, earlier intervention, and possible preventive
      measures could theoretically decrease stone recurrence and late complications.
      The majority of patients with common bile duct stone who have EST and stone
      clearance will have no further biliary events during the remainder of their life.
      Whether identifying risk factors for recurrence can improve outcomes by
      prophylactic treatments or earlier interventions needs further prospective study.

PMID- 16607139
TI  - "My patients are the sickest".
AB  - People with symptoms of the irritable bowel syndrome represent a broad spectrum
      with respect to severity of symptoms. Only a minority of them seek medical help
      and thereby become patients. The more severe are the symptoms that are
      experienced, the lower are the quality of life ratings, but patients will be more
      prone to participate in enquiries. This makes it very difficult to gain a
      representative picture of quality of life in irritable bowel syndrome.

PMID- 16607140
TI  - Risk factors for symptomatic stone recurrence after transpapillary laser
      lithotripsy for difficult bile duct stones using a laser with a stone recognition
      system.
AB  - BACKGROUND: Laser-induced shock-wave lithotripsy (LISL) is successfully used for
      the treatment of difficult bile duct stones. The aim of this study was to assess
      the long-term risk for a symptomatic bile duct stone recurrence after LISL and to
      detect risk factors predicting recurrence. METHODS: Between 1993 and 2001, 80
      patients with difficult bile duct stones were successfully treated by
      intracorporeal LISL through the papilla of Vater. Seventy-one of these patients
      [median age, 65.8 years; 51 women (71.8%)] were followed for a median (range)
      period of 58 (1-114) months. RESULTS: Eleven patients (15.5%) had a symptomatic
      stone recurrence. The median (range) period between laser lithotripsy and
      recurrence was 40 (5-85) months. The presence of a bile duct stenosis (P=0.032)
      and a body-mass index below 25 (P=0.025) were significantly associated with an
      increased risk for stone recurrence. A gallbladder in situ, the presence of
      gallbladder stones, dilation of the bile duct, or a peripapillary diverticulum
      was not associated with stone recurrence. CONCLUSIONS: The presence of a bile
      duct stenosis is significantly related to bile duct stone recurrence after
      treatment with LISL. The impact of the body mass index on stone recurrence is
      interesting. The gallbladder status did not predict stone recurrence in our
      study.

PMID- 16607141
TI  - Quality of life of patients with irritable bowel syndrome is low compared to
      others with chronic diseases.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent functional
      gastrointestinal dysmotility disorder. This study aimed to estimate the burden of
      illness of a Dutch population of community dwelling patients suffering from IBS.
      METHODS: Patients identified at community pharmacies, using mebeverine as a proxy
      for IBS, were administered a questionnaire regarding (1) the Rome II criteria for
      IBS, (2) predominant type of stool during complaints, (3) severity of symptoms
      (abdominal pain and discomfort), (4) generic and disease-specific quality of
      life, (5) current health status (utilities), and (6) loss of productivity.
      RESULTS: Three hundred and seventy-five users of mebeverine were identified of
      which 169 patients met the Rome II criteria for IBS, and were included in the
      study. More than half (58%) of the IBS patients reported severe abdominal pain
      and complaints. Generic and disease-specific quality of life outcomes showed
      impairment on all dimensions. Current health status in IBS patients, calculated
      on the basis of the EQ-5D VAS, was perceived on 62% of full health (95% CI, 60
      66%). A calculation of health status in these patients based on the SF-6D
      algorithm showed a comparable score of 0.67 (1 is full health; 95% CI, 0.65
      0.68). The loss in productivity of IBS patients was 1.8 days (95% CI, 1.1-2.5)
      per month. CONCLUSIONS: This study confirmed that the burden of illness of IBS in
      the Netherlands is substantial. IBS patients treated with mebeverine experienced
      low quality of life and suffered from severe pain. Based on these results, more
      attention for the diagnosis and treatment of IBS seems to be justified.

PMID- 16607142
TI  - The toxicity of high molecular weight glutenin subunits of wheat to patients with
      coeliac disease.
AB  - OBJECTIVES: The ability of the gliadin fraction of wheat gluten to exacerbate
      coeliac disease is well documented. We investigated the possible toxicity of high
      molecular weight glutenin subunits (HMW-GS) in coeliac disease in vitro using
      gluten-sensitive T cells, and in vivo with challenge studies in patient
      volunteers. METHODS: A mixture of four HMW-GS was chemically separated from wheat
      flour and checked for purity by HPLC, SDS-PAGE and ELISA. T-cell lines, grown up
      from small intestinal biopsies from coeliac patients (n=17), were tested for
      their reactivity to HMW-GS. Adults with coeliac disease and who were on a gluten
      free diet (n=3) underwent in-vivo challenges with HMW-GS. Duodenal biopsies,
      taken prior to the challenge and at intervals up to 6 h afterwards, were assessed
      for morphology, intra-epithelial lymphocyte count, and interleukin 15 (IL-15)
      expression, by immunohistochemistry. RESULTS: T-cell lines from 11 of 17 patients
      were stimulated by HMW-GS. There was a significant change in small intestinal
      morphology 4 h after commencing infusions with HMW-GS in all three subjects. For
      example villus height to crypt depth ratios were reduced in the three patients
      from 3.0+/-0.5 to 1.29+/-0.2, 2.53+/-0.7 to 0.81+/-0.6 and 3.0+/-0.7 to 1.85+/
      0.3, P<0.0001 in all cases. There was increased expression of IL-15 in the small
      intestine from 2 h after the HMW-GS challenges. CONCLUSION: Mixed HMW-GS
      stimulate T-cell lines from some coeliac patients and exacerbate coeliac disease
      in vivo, inducing expression, within 2 h, of IL-15. This suggests an innate
      immune response to these proteins.

PMID- 16607143
TI  - Diagnostic accuracy of coeliac serological tests: a prospective study.
AB  - OBJECTIVE: The best way to test serologically for coeliac disease (CD) remains
      controversial, with endomysial (EMA), transglutaminase (TTG), and gliadin
      antibodies (AGA) being assessed in various combinations with no apparent
      standardization. The objective of this study was to evaluate whether TTG-IgA+/
      TTG-IgG could be used as a replacement for endomysial antibodies as a reliable
      screen for CD in patients presenting to a major Australian tertiary referral
      hospital for assessment of symptoms consistent with CD. METHODS: Individuals
      referred for gastroscopic assessment of possible CD were prospectively evaluated
      by duodenal biopsy assessment. The following diagnostic methods were compared:
      dual-isotype transglutaminase (TTG-dual), combined-isotype transglutaminase (TTG
      IgA+G), TTG-IgA, combined-isotype gliadin antibodies (AGA-IgA+G), AGA-IgA, and
      endomysial antibody assays. Clinical performance characteristics (sensitivity,
      specificity, area under the curve for receiver-operating characteristic analysis;
      AUROC) were assessed for all kits. RESULTS: The correlation between
      transglutaminase kits was generally good, with the best transglutaminase kit
      demonstrating high correlation (r=0.86) with endomysial antibodies. A comparison
      of different types of endomysial antibody assays displayed variable diagnostic
      performance (sensitivity 61.90-68.42%; specificity 80.00-98.57%; AUROC 0.71
      0.83). Sensitivity (90.48-92.31%), specificity (80.77-82.89%) and AUROC values
      (0.92-0.94) for dual-isotype transglutaminase kits displayed narrow ranges. AGA
      assays were less sensitive (AGA-IgA: 42.31-46.15%; AGA-IgG: 61.54%) and less
      specific (AGA-IgA: 85.09-87.73%; AGA-IgG: 82.46-84.09%). Dual-isotype
      transglutaminase testing was diagnostically equivalent to transglutaminase-IgA
      (AUROC 0.92 versus 0.91, P=0.33). CONCLUSIONS: Our study suggests that
      transglutaminase screening (using the IgA+/-IgG isotype) is a sensitive and
      specific alternative to endomysial antibody testing in the serological assessment
      of CD. On the basis of our findings, AGA antibody testing no longer appears to be
      an essential part of the diagnostic strategy for adult CD.

PMID- 16607144
TI  - Longitudinal follow-up examination of antigliadin antibody positive children and
      adults.
AB  - BACKGROUND: We previously investigated the prevalence of asymptomatic celiac
      disease in 3004 healthy children and 4313 adult blood donors by screening for IgA
      and IgG class antigliadin antibodies (AGA) and IgA class anti-endomysial
      antibodies (EmA). In none of the 162 exclusive AGA-positive adults and in only
      one of the 117 exclusive AGA-positive children could celiac disease be diagnosed.
      We followed up AGA-positive individuals in respect of the significance of the
      AGA. METHODS: All AGA-positive children and adults were invited for a follow-up
      clinical examination and laboratory investigations including AGA-IgA, AGA-IgG and
      EmA. Celiac disease-specific antibodies were also determined in stool samples.
      RESULTS: Sixty-nine adults and 47 children returned for follow-up. In 26 (37.7%)
      cases of the 69 adults formerly tested AGA-positive, AGA were still detectable
      after an average period of 3.7 years. In 21 (44.7%) cases of 47 formerly AGA
      positive children, AGA were still detectable after an average period of 4.3
      years. None of the 69 adults and 47 children showed seroconversion to EmA. There
      were no significant abnormalities in the laboratory results or any clinical signs
      of enteropathy. The appearance of fecal and serum antibodies was compared in 112
      subjects but no correlation between fecal and serum antigliadin antibodies was
      found. CONCLUSIONS: In both studied populations of adults and children, AGA
      disappeared in more than 50% of the cases. The appearance of AGA has to be
      interpreted as a non-specific immunomodulation phenomenon, confirming the low
      specificity of AGA as a serologic marker for celiac disease.

PMID- 16607145
TI  - Colonic propulsive and postprandial motor activity in patients with ulcerative
      colitis in remission.
AB  - BACKGROUND: Although it is known that colon motility is abnormal in ulcerative
      colitis, data are still scarce with regard to the underlying mechanisms. Recent
      evidence suggests that the propulsive activity is highly increased during the
      active phase of the disease, probably contributing to the diarrhoea. However,
      data are even scarcer in the quiescent phase of the disease. AIMS: To assess the
      colonic high-amplitude and low-amplitude propulsive activity and the colonic
      motor response to eating in patients with ulcerative colitis in remission.
      PATIENTS AND METHODS: Fourteen patients were recruited, all with the disease in
      remission as documented by clinical and endoscopic criteria. Twenty-four hour
      manometric recordings were obtained in these patients, and compared to those of
      16 healthy controls. RESULTS: The high-amplitude propagated contractions were
      similar in both groups (5.8+/-2.6 events in ulcerative colitis patients and 5.5+/
      0.8 in controls (P=0.13)), whereas patients tended to display a higher number of
      low-amplitude propagated events (134.4+/-34 vs. 60.9+/-16 in controls (P=0.058)).
      No differences were found in the colonic motor response to eating between
      patients and controls. CONCLUSIONS: Colonic propulsive activity in ulcerative
      colitis in remission is almost normal, even though the low-amplitude propagated
      activity tends to be similar to that observed in patients with the irritable
      bowel syndrome, thus possibly contributing to the persistence of abdominal
      symptoms in a subgroup of patients.

PMID- 16607146
TI  - Evaluation of triple and quadruple Helicobacter pylori eradication therapies in
      Iranian children: a randomized clinical trial.
AB  - BACKGROUND: Clinical trials in children concerning Helicobacter pylori
      eradication treatments are scarce. The purpose of this study was to assess the
      efficacy of proton pump inhibitor (PPI)-based triple therapy using PPI,
      amoxicillin and clarithromycin in Iranian children. We also evaluated the
      efficacy of quadruple therapy with PPI, metronidazole, amoxicilin and bismuth
      citrate in Iranian children. METHODS: This was a randomized clinical trial
      performed in Emam Khomeini Hospital between 2003 and 2004. Patients with
      confirmed H. pylori infection by histology were divided into two groups in a
      randomized 1:1 scheme: the triple regimen group (omeprazole, clarithromycin and
      amoxicillin for 10 days) and the quadruple regimen group (omeprazole,
      amoxicillin, metronidazole and bismuth citrate for 10 days). The eradication was
      assessed by the C-urea breath test 4 weeks after the end of treatment and
      analyzed by per-protocol and intention-to-treat approaches. RESULTS: One hundred
      and twenty-two patients (mean age 12.36+/-3.06 years) were entered into the
      study. Only 100 patients completed the study (50 patients in each regimen group).
      The eradication rates by triple therapy were 92% and 75.5% for the "per-protocol"
      and "intention-to-treat" approaches, respectively. In the quadruple regimen
      group, the eradication rates were 84% by the per-protocol approach and 68.8% in
      the intention-to-treat approach. Symptom responses to therapy were reported in
      all patients with successful eradication (88% of all patients). CONCLUSION: With
      regard to recent recommendations, we also suggest PPI, amoxicillin and
      clarithromycin triple therapy as a first-line eradication treatment, and
      quadruple therapies as a second-line option, in Iranian children.

PMID- 16607147
TI  - Long-term outcomes after Helicobacter pylori eradication with second-line,
      bismuth-containing quadruple therapy in Korea.
AB  - OBJECTIVES: To determine the long-term outcomes in terms of Helicobacter pylori
      and ulcer recurrence after second-line eradication with bismuth-containing
      quadruple regimens in Korea. METHODS: Sixty-seven patients with peptic ulcer
      disease after successful eradication using second-line quadruple therapies were
      prospectively followed up 1 month after treatment and then every 6 months or when
      dyspeptic symptoms reappeared to ascertain H. pylori and ulcer status. RESULTS:
      Three patients were lost during follow-up. The median duration of follow-up of
      the remaining 64 patients was 26.8 months. H. pylori recurrence occurred in 11 of
      these 64 patients (17.2%), giving a calculated reinfection rate of 6.0% per
      patient-year. Only one of the 11 patients was reinfected by 12 months after
      treatment completion. Four of 11 patients (36.4%) who became reinfected
      experienced peptic ulcer recurrence, but none of 53 patients who were not
      reinfected experienced recurrence. No evidence was obtained to indicate that the
      reinfection rate depended on the age, sex, ulcer location, or eradication
      regimens. The relapse of dyspeptic symptoms was the only factor predictive of H.
      pylori recurrence. CONCLUSION: This study suggests that the recurrence rate of H.
      pylori at 1 year after second-line, bismuth-containing quadruple therapy is low,
      but the annual reinfection rate is as high as 6%. Surveillance for H. pylori
      reinfection facilitating peptic ulcer recurrence may be warranted even after a
      second eradication, especially when dyspeptic symptoms reappear in Korea.

PMID- 16607148
TI  - Does alpha1-antitrypsin phenotype PiMZ increase the risk of fibrosis in liver
      disease due to hepatitis C virus infection?
AB  - BACKGROUND: The factors influencing the development of hepatic fibrosis, a key
      factor in determining outcome, are incompletely understood in hepatitis C. It has
      been suggested that the heterozygous Z mutation of the alpha1-antitrypsin gene
      (PiMZ) predisposes to more severe liver damage when infected by the hepatitis C
      virus. This retrospective cross-sectional study was designed to compare the
      prevalence of PiMZ in hepatitis C patients with different degrees of fibrosis.
      PATIENTS AND METHODS: One hundred and forty-one patients from the Trent Hepatitis
      C Study Group's database were selected for study. Forty-six had no fibrosis on
      liver biopsy, 53 had cirrhosis and 42 had intermediate fibrosis. The alpha1
      antitrypsin phenotype was determined by isoelectric focusing. RESULTS: There was
      no significant difference between the prevalence of PiMZ in the three groups-
      there was just one patient in each group. Comparing those with no fibrosis with
      those with cirrhosis, the odds ratio was 0.87 (95% confidence interval, 0.05-14).
      CONCLUSION: Our results do not support the hypothesis that the presence of the
      PiMZ phenotype predisposes to more severe fibrosis in patients with hepatitis C.

PMID- 16607149
TI  - Clinical significance of serum procalcitonin levels in patients with acute or
      chronic liver disease.
AB  - OBJECTIVE: To evaluate the diagnostic value of serum procalcitonin levels in
      patients with acute or chronic liver disease, with or without bacterial
      infections and to correlate the results with the clinical outcome and the
      laboratory findings for these patients. METHODS: One hundred and six consecutive
      hospitalized patients with liver disease were evaluated for procalcitonin levels
      on admission. Fifteen of them (14.2%) had acute alcoholic hepatitis on cirrhotic
      background (group A), 20 (18.9%) had alcoholic cirrhosis without hepatitis and/or
      bacterial infection (group B), 16 (15.1%) had decompensated cirrhosis with proved
      bacterial infection (group C), 42 (39.6%) had uncomplicated viral hepatitis
      related cirrhosis (group D) and 13 (12.3%) had acute icteric viral hepatitis
      (group E). Serum procalcitonin levels were measured using an immunoluminometric
      assay. Statistical analysis was based on Student's t-test and the non-parametric
      Kruskall-Wallis test (P<0.05). RESULTS: Serum procalcitonin levels were
      significantly higher in cirrhotic patients with bacterial infection (9.80+/-16.80
      ng/ml) than in those without bacterial infection (0.21+/-0.13 ng/ml, P=0.001),
      whereas they were within normal range (<0.5 ng/ml) in all patients with
      uncomplicated cirrhosis, irrespective of the cause of cirrhosis. Seven of 15
      group A patients (46.2%) and 4/13 group E patients (30.8%), all of them
      cirrhotics, had procalcitonin levels higher than 0.5 ng/ml on admission, without
      established bacterial infection. CONCLUSION: Serum procalcitonin levels remain
      below the threshold of 0.5 ng/ml in all patients with uncomplicated cirrhosis,
      irrespective of the cause of the disease, while they are significantly elevated
      when bacterial infection complicates the course of the disease. A significant
      proportion of patients with acute alcoholic hepatitis on a cirrhotic background
      as well as of patients with acute on chronic viral hepatitis, without bacterial
      infection, exhibit serum procalcitonin levels above 0.5 ng/ml, suggesting that
      this cut-off value is probably not enough to discriminate between patients with
      or without bacterial infection within these subgroups of patients with liver
      disease.

PMID- 16607150
TI  - High incidence of fermentation in the digestive tract in patients with reflux
      oesophagitis.
AB  - OBJECTIVES: Because bacteria represent the sole source of gut hydrogen (H2) and
      methane (CH4), fasting breath H2 and CH4 gases have been used as markers of
      colonic fermentation. The presence of carbohydrates in the colonic lumen inhibits
      gastric and pancreatic secretions, and also influences lower oesophageal
      sphincter function in gastro-oesophageal reflux disease. MATERIALS AND METHODS:
      Studies were performed in 793 consecutive patients undergoing
      oesophagogastroscopy (270 men and 523 women, aged 19-85 years). A fasting breath
      sample (20 ml) was collected before endoscopy. At endoscopy, we intubated the
      stomach without inflation by air, and 20 ml of intragastric gas was collected
      through the biopsy channel. Next, the tip of the endoscope was inserted into the
      second portion of the duodenum without inflation by air, and 20 ml of
      intraduodenal gas was collected. H2 and CH4 concentrations of each sample were
      measured by gas chromatography. RESULTS: Reflux oesophagitis was found in 147 of
      the 793 patients. The mean values of the H2 and/or CH4 levels of samples taken
      from the stomach, duodenum and exhaled air were higher in patients with reflux
      oesophagitis than those without reflux oesophagitis. High H2 and/or CH4 levels
      were more frequently found in patients with reflux oesophagitis. CONCLUSIONS: We
      concluded that the presence of fermentation in the digestive tract was considered
      to be a risk factor for developing reflux oesophagitis.

PMID- 16607151
TI  - Primary pancreatic Burkitt's lymphoma mimicking carcinoma with obstructive
      jaundice and very high CA19-9.
AB  - Primary pancreatic lymphoma is a rare neoplasm. We report the case of a 49-year
      old man who presented with biliary obstruction due to a neoplasm involving the
      pancreatic head. Initial computed tomography revealed a suspicious periampullary
      mass. Consequently, magnetic resonance imaging was performed 16 days later,
      showing a relatively clearly defined and homogeneous signal mass in the
      pancreatic head with biliary dilatation on enhanced study. In combination with
      high tumour marker associated antigen CA19-9 levels (1872 and 2110 U/ml), these
      findings were highly suggestive of a pancreatic carcinoma. He underwent Whipple's
      procedure. Examination of the surgical specimen revealed a Burkitt's lymphoma.
      This case demonstrates that lymphoma can present with features mimicking
      pancreatic head carcinoma on imaging, clinical and laboratory studies. Neither
      clinical nor imaging nor laboratory methods indicate correct diagnosis, but a
      relatively clearly defined and homogeneous mass should prompt the physician to
      include lymphoma in a differential diagnosis of a pancreatic mass.

PMID- 16607152
TI  - Herpes simplex virus type 1 colitis in a patient with common variable
      immunodeficiency syndrome.
AB  - We report on a case of herpes simplex virus (HSV) type 1 colitis in a 69-year-old
      patient with common variable immunodeficiency syndrome. A treatment with
      polyvalent immunoglobulins was discontinued in April 2001. In March 2004 she
      developed chronic diarrhoea related to rectosigmoidal and caecal ulcerations. In
      November 2004, HSV was recovered in tissue culture from colonic biopsies.
      Valaciclovir was then started, leading the patient to clinical remission at day
      4, and continued for a 6-week course (without any secondary antiviral
      prophylaxis). Colonic biopsies were negative for HSV by tissue culture and PCR
      within 3 weeks of antiviral treatment. Intravenous polyvalent immunoglobulin
      infusions were readministered within the third week of antiviral treatment. She
      has declared no clinical event since this period. Three months after the
      antiviral treatment was achieved, a rectosigmoidoscopy showed an ad-integrum
      macroscopic and histological mucosal healing whereas PCR was negative for HSV in
      the colonic tissue. As a large proportion of patients with common variable
      immunodeficiency syndrome present not only as a humoral immunodeficiency but also
      as a defect in the cellular immunity compartment (with T-cell deficits), HSV, as
      well as cytomegalovirus, should be investigated in patients with common variable
      immunodeficiency syndrome presenting colitis.

PMID- 16607153
TI  - Refractory bleeding from portal hypertensive gastropathy: a further novel role
      for thalidomide therapy?
AB  - Bleeding from portal hypertensive gastropathy (PHG) can pose a therapeutic
      challenge. Thalidomide, which selectively inhibits tumour necrosis factor-alpha
      production by enhancing messenger RNA degradation, has been shown to reduce
      portal venous pressure in cirrhotic and non-cirrhotic portal hypertension.
      Thalidomide is also a potent inhibitor of angiogenesis. We describe a case of
      intractable bleeding from PHG secondary to extrahepatic portal vein obstruction
      due to malignancy, which was managed successfully by thalidomide, thus obviating
      the need for major surgery. Although the use of thalidomide for treatment of
      severe intestinal bleeding has been described previously, this is the first case
      report, to our knowledge, describing its efficacy in bleeding secondary to PHG.
      We discuss the possible therapeutic mechanisms for thalidomide in PHG.

PMID- 16607154
TI  - Transjugular intrahepatic portosystemic shunt for the treatment of portal
      hypertension secondary to non-cirrhotic perisinusoidal hepatic fibrosis.
AB  - Non-cirrhotic perisinusoidal hepatic fibrosis is a process of imprecise
      pathogenesis involving collagenization of the space of Disse. Exposure to
      chemicals, auto-immunity, thrombophilia and/or infections are suspected primary
      agents. Here, we present the case of a patient who developed severe portal
      hypertension with histological features suggesting a non-cirrhotic perisinusoidal
      hepatic fibrosis. A 52-year-old man was hospitalized for oesophageal variceal
      haemorrhage. Liver cirrhosis or portal vein thrombosis were absent as attested by
      laboratory tests, duplex sonography, computed tomography scan and histological
      examination of a liver biopsy specimen. Presinusoidal portal hypertension was
      suggested by a normal wedge-free hepatic vein gradient. Only electron microscopy
      examination of a liver biopsy specimen could disclose perisinusoidal fibrosis.
      This was most probably secondary to a combined chemotherapy received 4 years
      earlier for non-Hodgkin large-cell lymphoma. As variceal ligation failed to
      control oesophageal varices while liver function tests were normal, a
      transjugular intrahepatic portosystemic shunt (TIPS) was performed. This
      dramatically improved the signs of portal hypertension. This case illustrates the
      use of TIPS in the treatment of portal hypertension secondary to non-cirrhotic
      perisinusoidal fibrosis.

PMID- 16607155
TI  - Nodular regenerative hyperplasia: a reversible entity associated with
      azathioprine therapy.
AB  - Azathioprine represents an effective and widely used immunosuppressant; however,
      there are increasing concerns about the hepatotoxicity of thiopurines because of
      an entity called "nodular regenerative hyperplasia" (NRH) observed in patients
      treated with 6-thioguanine. In line with this hypothesis, we report and comment
      on a patient with inflammatory bowel disease (IBD) diagnosed with NRH as a
      reversible but potentially serious hepatotoxic side-effect of azathioprine. Our
      report strengthens the importance of further safety studies to evaluate the
      aetiology and prevalence of NRH in IBD patients before general conclusions on the
      use of thiopurines can be drawn. Physicians caring for IBD patients need to be
      alert to this rare but serious complication.

PMID- 16607156
TI  - McKittrick-Wheelock syndrome: a rare cause of diarrhoea.
AB  - McKittrick-Wheelock syndrome is a rare disorder caused by fluid and electrolyte
      hypersecretion from a rectal tumour. The most frequently reported tumours are
      villous adenomas. Dehydration with severe hyponatremia, hypokalemia, metabolic
      acidosis, acute renal failure and watery diarrhoea is typical. The authors
      present a case of McKittrick-Wheelock syndrome caused by rectal adenocarcinoma.

PMID- 16607157
TI  - Acquired intestinal lymphangiectasia successfully treated with a low-fat and
      medium-chain triacylglycerol-enriched diet in a patient with liver
      transplantation.
AB  - Intestinal lymphangiectasia is defined as a dilatation of small bowel lymphatic
      capillaries and a loss of lymph into the bowel lumen. Clinically it is
      characterized by hypoproteinaemia and oedema. We present here a case of protein
      losing enteropathy due to intestinal lymphangiectasia after liver transplantation
      in a 57-year-old man who was transplanted for hepatitis C virus. Four years after
      liver transplantation, the patient developed hypoalbuminaemia and ascites
      associated with recurrence of cirrhosis. The sudden fall in serum albumin led us
      to look for a cause of reduction other than or in addition to cirrhosis. Duodenal
      biopsies showed tall villi with dilated lymphatic vessels and widening of the
      villi caused by oedema, demonstrating intestinal lymphangiectasia. In this case a
      low-fat diet supplemented with medium-chain triacylglycerols achieved an early
      clinical improvement with increased serum albumin levels and ascites
      disappearance. Intestinal lymphangiectasia should be suspected in liver
      transplanted patients developing hypoproteinaemia and hypoalbuminaemia after the
      recurrence of cirrhosis.

PMID- 16607158
TI  - Neurological symptoms suggestive of demyelination in Crohn's disease after
      infliximab therapy.
AB  - Anti-TNFalpha drugs are currently used in the treatment of patients with Crohn's
      disease. Studies have reported neurological side effects occurring after anti
      TNFalpha treatment, including infliximab-induced complications.

PMID- 16607159
TI  - The significance of ileocolonic lymphoid nodular hyperplasia in children with
      autistic spectrum disorder.

PMID- 16607161
TI  - Noni juice protects the liver.

PMID- 16607166
TI  - RSO Interview with Marcum Martz. Interview by Rene Michel.

PMID- 16607163
TI  - Prevalence of prolonged prothrombin time in children with coeliac disease.

PMID- 16607167
TI  - The story behind the story, or there's lemonade in the water cooler today.

PMID- 16607168
TI  - ATE evolution: becoming your resource.
AB  - The Health Physics Society (HPS) Web site was created in 1996 to further the HPS
      mission of promoting communication among people who conduct radiation safety
      activities; to encourage scientific, professional, and public education; and to
      disseminate sound scientific information. In 1999, a new feature called "Ask the
      Experts" (ATE) was added allowing individuals from around the world to pose
      questions concerning radiological protection. With the help of four editors, 20
      topic editors, and 125 subject experts, nearly 5,000 questions have been
      answered. Response to questions submitted is rapid with the topic editor
      corresponding directly with the questioner. Most responses involve only one
      interaction although there may be follow-up interactions to fully resolve issues
      in the questioner's mind. Experts must provide prompt, valuable, and sound
      scientific answers in an easy-to-understand manner. The ATE feature is the most
      popular on the HPS Web site. With a current average of three questions submitted
      each day (including weekends), it became increasingly difficult for a person
      browsing the Web site to find information among the many posted questions and
      answers. Because of this difficulty, some questions were being asked repeatedly.
      It was decided to redesign the ATE feature to make the process of finding
      information easier. Answer categories were merged, eliminated, added, or reduced
      in size. "Frequently Asked Questions" (FAQs) or information sheets were
      developed. As a result, 36 categories became 25, and 18 FAQs, 22 information
      sheets, and 8 reference sheets were created to provide useful information
      resources for HPS members, radiation safety professionals, and the public.

PMID- 16607169
TI  - A primer on the requirements for select agents and toxins used in biomedical and
      agricultural research applications.
AB  - A basic overview of the U.S. Department of Health and Human Services and U.S.
      Department of Agriculture List of Regulated Select Agents and Toxins used in
      biomedical and agricultural research, as controlled by the Centers for Disease
      Control and Prevention, is presented. The objective of the primer is to introduce
      to the health physics community a brief history, discuss basic terminology,
      review current legislation, and describe rules and regulations for the
      possession, use, and transfer of select agents and toxins. As with many
      institutions facing staff and budget restrictions, there is increased frequency
      of health physics professionals being designated the Responsible Official. This
      summary is necessary since radiolabeled select agents and toxins are being
      utilized in research applications and require oversight by the health physicist.

PMID- 16607170
TI  - An analysis of 20 years of radiation-related health care complaints in Texas for
      the purposes of quality improvement.
AB  - In an effort to reveal the possible underlying causes of radiation-related health
      care complaints in the State of Texas, complaint data were evaluated using
      historical Texas Department of Health-Bureau of Radiation Control (TDH-BRC)
      reports. A major aim of the study was to generate a summary of the most commonly
      reported complaints that might be generalized to health care providers using
      sources of radiation across Texas. A generalizable list of common complaints
      would be a valuable tool for education and prevention programs, serving to
      possibly reduce the overall incidence of radiation-related medical complaints.
      Descriptive text summary reports of complaints were obtained from the TDH-BRC for
      the 20-y period inclusive of 1981 to 2001. The information was systematically
      coded into a computerized database. During the 20-y period of study, 481 health
      care-related complaints were identified, with approximately 74% consisting of
      claims of an "uncredentialed technician" (39%), "overexposure" (21%), or
      "regulatory violation" (14%). The most common categories of complaints imply some
      patient understanding or knowledge of the credentialing requirements of workers,
      the applicable dose limits, or the regulatory requirements associated with
      medical procedures. Since it is unlikely that an average patient would be aware
      of such issues, the findings suggest the complaints are not actually indications
      of the inappropriate uses of radiation, but are rather based on the patient's
      broader perception of services rendered. Most of the complaints levied during the
      period of study were done so anonymously (58%) and were levied against a generic
      facility (61%) rather than a specific technician (5%), doctor (4%), or student
      (1%). Approximately 61% of the complaints resulted in the issuance of a notice of
      violation upon investigation by the TDH-BRC, but the available data did not
      permit definitive linkage between the initial complaint and the violation issued.
      Taken in aggregate, the analysis suggests that improved communications between
      health care providers and the patients they serve could possibly serve to prevent
      future complaints. Although the analysis was limited to the data from a single
      state, the results may be of use to quality assurance programs on a broader scale
      because of the objective identification of likely common issues. Possible options
      for improving the means of systematically collecting initial compliant data in
      the future are also discussed.

PMID- 16607171
TI  - A review of educational philosophies as applied to radiation safety training at
      medical institutions.
AB  - This paper examines the educational philosophy of radiation safety education
      programs at medical institutions. The regulatory mandates for radiation safety
      training have traditionally emphasized competency-based training. This emphasis
      led to the adoption of a behaviorist philosophy that requires predetermined
      responses to certain situations. The behaviorist approach determines the roles of
      teacher and learner as well as the methods to be used. This paper examines these
      roles and methods and the influence of a highly regulated environment on the
      adoption of the behaviorist model. The paper also suggests that other educational
      philosophies, such as the progressive philosophy, should be examined to provide a
      rich foundation for improving the educational experience and outcomes.

PMID- 16607172
TI  - Simulating gaseous 131I distribution in a silver zeolite cartridge using sodium
      iodide solution.
AB  - 131I is one of the most significant gaseous fission products in a nuclear power
      plant. Because of its high volatility at room temperature, iodine can be easily
      inhaled by radiation workers following release of radioiodine into the
      atmosphere. The thyroid gland is the critical organ for iodine uptake and is
      subject to radioiodine carcinogenesis. Hence, monitoring systems are provided in
      nuclear power plants to sample and evaluate ambient air for gaseous radioiodine
      content. Due to a highly preferential retention efficiency for iodine gas
      compared to noble gases, silver zeolite cartridges are typically used in nuclear
      power plants to adsorb gaseous iodine for sampling purposes. To obtain accurate
      measurements, preparation of a proper calibration standard to simulate the
      gaseous radioiodine distribution in the cartridge is essential. This project
      developed a silver zeolite cartridge calibration standard that uses sodium iodide
      solution to simulate gaseous iodine distribution. This calibration standard
      appears to satisfactorily simulate the gaseous radioiodine distribution in the
      silver zeolite cartridge.

PMID- 16607173
TI  - Neutron-based sterilization of anthrax contamination.
AB  - With the anthrax threat becoming a reality, it is very important to have an
      effective way to sterilize areas contaminated by anthrax. Anthrax spores are the
      dormant form of the anthrax bacteria. They can germinate in tissues, producing
      new bacteria that release lethal toxins. Neutrons can be a powerful tool in our
      defense against anthrax contamination. Neutrons are elementary particles that
      have no charge, which allows them to be very penetrating, killing the anthrax
      spores on the surface and inside the containers. So neutrons have an advantage
      over other forms of radiation if deep penetration is required to kill biological
      organisms. A Cf neutron source allows for a low cost method of decontamination.
      It emits most neutrons in the 100 keV to 2 MeV energy regions, and a neutron in
      this energy region is 20 times more deadly than electrons or gamma rays in
      killing anthrax spores. If we just consider the first neutron collision with
      anthrax spores and that all the anthrax spores will not survive at the dose level
      above 2.0 x 10 Gy, our calculations show that a 0.5-g Cf neutron source within 20
      min can generate 1.11 x 10 m fluence neutrons, which is good enough to kill the
      anthrax spores on the sample. An experimental confirmation of the above results
      may prove that to achieve 1.11 x 10 m fluence neutrons on the anthrax spore
      sample, the neutron irradiation time may be reduced dramatically or the Cf
      neutron source reduced to 0.1 g level or even less. The aim of this paper is to
      evaluate a feasible way to sterilize the anthrax contamination by using a Cf
      neutron source. Presently, we are mainly concentrating on the theoretical
      estimation of neutron fluence to see if the Cf neutron source can deliver enough
      neutron irradiation dose to kill the anthrax spores. Our future work will focus
      on experimental confirmation and Monte Carlo simulation by using Geant4 or MCNP
      codes. At that time, we will consider the effects of the real experimental setup,
      the shielding materials, the exact chemical components, and the biological
      structures of anthrax spores. We also need to consider the ways of carrying the
      anthrax spores, and this includes surface contamination, inside an envelope, or
      hidden in sealed metal containers and luggage.

PMID- 16607174
TI  - A comprehensive dose reconstruction methodology for former rocketdyne/atomics
      international radiation workers.
AB  - Incomplete radiation exposure histories, inadequate treatment of internally
      deposited radionuclides, and failure to account for neutron exposures can be
      important uncertainties in epidemiologic studies of radiation workers. Organ
      specific doses from lifetime occupational exposures and radionuclide intakes were
      estimated for an epidemiologic study of 5,801 Rocketdyne/Atomics International
      (AI) radiation workers engaged in nuclear technologies between 1948 and 1999. The
      entire workforce of 46,970 Rocketdyne/AI employees was identified from 35,042
      Kardex work histories cards, 26,136 electronic personnel listings, and 14,189
      radiation folders containing individual exposure histories. To obtain prior and
      subsequent occupational exposure information, the roster of all workers was
      matched against nationwide dosimetry files from the Department of Energy, the
      Nuclear Regulatory Commission, the Landauer dosimetry company, the U.S. Army, and
      the U.S. Air Force. Dosimetry files of other worker studies were also accessed.
      Computation of organ doses from radionuclide intakes was complicated by the
      diversity of bioassay data collected over a 40-y period (urine and fecal samples,
      lung counts, whole-body counts, nasal smears, and wound and incident reports) and
      the variety of radionuclides with documented intake including isotopes of
      uranium, plutonium, americium, calcium, cesium, cerium, zirconium, thorium,
      polonium, promethium, iodine, zinc, strontium, and hydrogen (tritium). Over
      30,000 individual bioassay measurements, recorded on 11 different bioassay forms,
      were abstracted. The bioassay data were evaluated using ICRP biokinetic models
      recommended in current or upcoming ICRP documents (modified for one inhaled
      material to reflect site-specific information) to estimate annual doses for 16
      organs or tissues taking into account time of exposure, type of radionuclide, and
      excretion patterns. Detailed internal exposure scenarios were developed and
      annual internal doses were derived on a case-by-case basis for workers with
      committed equivalent doses indicated by screening criteria to be greater than 10
      mSv to the organ with the highest internal dose. Overall, 5,801 workers were
      monitored for radiation at Rocketdyne/AI: 5,743 for external exposure and 2,232
      for internal intakes of radionuclides; 41,169 workers were not monitored for
      radiation. The mean cumulative external dose based on Rocketdyne/AI records alone
      was 10.0 mSv, and the dose distribution was highly skewed with most workers
      experiencing low cumulative doses and only a few with high doses (maximum 500
      mSv). Only 45 workers received greater than 200 mSv while employed at
      Rocketdyne/AI. However, nearly 32% (or 1,833) of the Rocketdyne/AI workers had
      been monitored for radiation at other nuclear facilities and incorporation of
      these doses increased the mean dose to 13.5 mSv (maximum 1,005 mSv) and the
      number of workers with >200 mSv to 69. For a small number of workers (n=292),
      lung doses from internal radionuclide intakes were relatively high (mean 106 mSv;
      maximum 3,560 mSv) and increased the overall population mean dose to 19.0 mSv and
      the number of workers with lung dose>200 mSv to 109. Nearly 10% of the radiation
      workers (584) were monitored for neutron exposures (mean 1.2 mSv) at
      Rocketdyne/AI, and another 2% were monitored for neutron exposures elsewhere.
      Interestingly, 1,477 workers not monitored for radiation at Rocketdyne/AI (3.6%)
      were found to have worn dosimeters at other nuclear facilities (mean external
      dose of 2.6 mSv, maximum 188 mSv). Without considering all sources of
      occupational exposure, an incorrect characterization of worker exposure would
      have occurred with the potential to bias epidemiologic results. For these
      pioneering workers in the nuclear industry, 26.5% of their total occupational
      dose (collective dose) was received at other facilities both prior to and after
      employment at Rocketdyne/AI. In addition, a small number of workers monitored for
      internal radionuclides contributed disproportionately to the number of workers
      with high lung doses. Although nearly 12% of radiation workers had been monitored
      for neutron exposures during their career, the cumulative dose levels were small
      in comparison with other external and internal exposure. Risk estimates based on
      nuclear worker data must be interpreted cautiously if internally deposited
      radionuclides and occupational doses received elsewhere are not considered.

PMID- 16607175
TI  - Cancer mortality among populations residing in counties near the Hanford site,
      1950-2000.
AB  - A descriptive epidemiologic study of cancer mortality among residents of counties
      near the Hanford nuclear facility site in Richland, Washington, was conducted.
      Between 1944 and 1957, radioactive 131I was released into the environment from
      the Hanford site. Cancer mortality from 1950 through 2000 was evaluated in four
      counties with the highest estimated exposure to 131I and compared with the cancer
      mortality experience in five demographically similar counties in Washington State
      with minimal 131I exposure. Overall, cancer rates in the study counties were
      slightly below those in the comparison counties [relative risk (RR) 0.95; 95%
      confidence interval (CI) 0.93-0.97], due mainly to a low risk for lung cancer (RR
      0.89; 95% CI 0.85-0.93). Thyroid cancer (n=33; RR 0.84; 95% CI 0.56-1.26), female
      breast cancer (n=1,233; RR 0.99; 95% CI 0.92-1.06), leukemia other than chronic
      lymphocytic leukemia (n=492; RR 0.95; 95% CI 0.85-1.06), and childhood leukemia
      (n=71; RR=1.06; 95% CI 0.78-1.43) were not significantly increased in the exposed
      counties. Furthermore, there was no evidence that the cancer death rates over
      time differed between study and comparison counties. Patterns over time of
      thyroid cancer in particular were similar for exposure and comparison counties.
      Although based on a geographic correlation design, these data suggest that living
      near the Hanford site has not increased cancer rates.

PMID- 16607176
TI  - Ecological half-time and effective dose from chernobyl debris and from nuclear
      weapons fallout of 137Cs as measured in different Swedish populations.
AB  - The fallout in Sweden of radiocesium from nuclear weapons tests during the 1960's
      (137Cs) and from the Chernobyl accident in 1986 (134Cs and 137Cs) has transferred
      to humans through different ecological pathways. Data from whole-body burden
      measurements of 134Cs, 137Cs, and 40K in various Swedish populations between 1964
      and 2002 have been compiled. This database enables an evaluation of the temporal
      and geographical dependence of the transfer of radiocesium from ground deposition
      to humans and the associated absorbed dose. The body burdens of 137Cs gradually
      decrease after the peak values reached in 1965 from nuclear weapons fallout and
      in 1987 from the Chernobyl fallout, but at a varying rate depending on the
      population. Assuming a dual exponential decrease, a short-term component of
      typically 1-2 y and a long-term component of 5-10 y are found in urban
      populations in Sweden. Among reindeer herders and hunters the effective
      ecological half-time is mono-exponential with a half-time of 5-7 y. The estimated
      time-integrated effective dose to an individual during a period of 50 y from the
      Chernobyl fallout is, on average, approximately 10 mSv for reindeer herders,
      which is 10-100 times higher than the estimated dose received by urban
      populations in the three major Swedish urban areas (Malmo, Goteborg, and
      Stockholm).

PMID- 16607177
TI  - Americium in the beagle dog: biokinetic and dosimetric model.
AB  - A biokinetic model of the systemic distribution of americium in the beagle dog is
      presented. The model is based on a previous biokinetic model of plutonium. The
      data sets used for the development of the model were the measurements of excreted
      activity (urine and feces) and organ burdens (skeleton, liver, and other soft
      tissues) for different levels of initial injected activity. In developing the
      model, the compartmental structure of the skeleton of the plutonium model was
      adopted, and only the numerical values of parameters were adapted. The model well
      describes the fractions of americium in the skeleton, liver, and soft tissues and
      the total fraction excreted in urine and feces. The tuning of the liver clearance
      parameter provides a realistic description of the change in the partitioning
      between liver and skeleton for different injection levels. The most significant
      features of the biokinetics and dosimetry of americium and plutonium in beagles
      are compared. The total fractions of the clearance to the skeleton and the liver
      are roughly equal to the value for plutonium, but the partitioning of americium
      between these organs is reversed with respect to the partitioning of plutonium.
      241Am doses to liver and skeleton are similar to 239Pu doses, owing to some
      counteracting factors. For the highest injection level, the liver mass is
      dependent on the time post injection. For the skeletal tissues, the dose to the
      cortical endosteum by far exceeds the dose to the trabecular endosteum and the
      red marrow. The model provides the basis for statistical survival analyses and
      risk estimates.

PMID- 16607178
TI  - Physical models and limits of radionuclides for decorative building materials.
AB  - In the past, the external exposure dose model for soil (the soil's physical
      model) was used to calculate the doses of decorative building materials because
      there was no materials model. In this paper, physical models are proposed to
      calculate the absorbed dose rates in air from decorative building materials by
      Monte Carlo simulation with the EGSnrc code. The physical models of this paper
      greatly differ from physical models for soil. The good agreement between
      simulations and measured absorbed dose rate in indoor air indicates that the
      results obtained by the Monte Carlo simulations are realistic. The absorbed dose
      rates in air calculated by physical models for soil are much higher than the
      measured dose rates. According to the reports of UNSCEAR 2000 and ICRP 1999, the
      limits of radionuclides in some kinds of decorative building materials were
      deduced by using the physical models for materials presented in our work. The
      limits of every kind of decorative building material from our work are different.

PMID- 16607179
TI  - Retinal injury thresholds for blue wavelength lasers.
AB  - The interaction mechanism leading to laser-induced retinal alteration can be
      thermal or non-thermal, depending upon the wavelength of the laser radiation and
      the duration of the exposure. To investigate the effect of exposure duration on
      the interaction mechanism, retinal injury thresholds in the rhesus monkey were
      experimentally measured for exposure to laser radiation at wavelengths of 441.6,
      457.9, 476.5, and 496.5 nm. Exposure durations were 0.1, 1, 5, 16, and 100 s; and
      1/e retinal irradiance diameters were 50, 125, and 327 microm. Tissue response
      was observed via ophthalmoscope 1 h and 48 h post exposure. Thermal and non
      thermal damage thresholds were obtained depending upon the exposure duration.
      These threshold data are in agreement with data previously reported in the
      literature for 100-s duration exposures, but differences were noted for shorter
      exposures. The current study yielded an estimated injury threshold for 1-s
      duration, 327-microm retinal irradiance diameter exposures at 441.6 nm, which is
      an order of magnitude higher than that previously reported. This study provides
      evidence that laser-induced retinal damage is primarily induced via thermal
      mechanisms for exposures shorter than 5 s in duration. Arguments are presented
      that support an amendment of the thermal hazard function, R(lambda).

PMID- 16607180
TI  - Modeling radiological dose in non-human species: principles, computerization, and
      application.
AB  - Due to the increasing interest in environmental protection against ionizing
      radiation on the international scene, the need for operational tools for
      radiological environmental risk assessment is becoming critical. Within this
      framework, this paper puts forward a fast and user-friendly computerized method
      to allow the transformation from exposure (expressed in Bq per unit of mass or
      volume) to dose (i.e., the energy deposited in the organism, expressed in Gy)
      received from any radionuclide by any non-human species, for a unit of time and a
      unit of "concentration" of radionuclide in the radiation source. The calculation
      principles used to determine this dose coefficient, expressed in Gy/unit of time
      per Bq/unit of volume or mass, are described for gamma, beta, and alpha
      radiation. Both internal and external exposure situations are considered. The
      domain of validity of the proposed model is specified, as is the way in which it
      has been computerized. The paper concludes by verifying the numerical accuracy of
      the tool and making initial comparisons between results from the described method
      and those developed at the European level.

PMID- 16607181
TI  - Determination of natural and depleted uranium in urine at the ppt level: an
      interlaboratory analytical exercise.
AB  - An analytical exercise was initiated in order to determine those procedures with
      the capability to measure total uranium and uranium (238U/235U) isotopic ratios
      in urine samples containing >0.02 microg U kg-1 urine. A host laboratory prepared
      six identical sets of twelve synthetic urine samples containing total uranium in
      the range of 25 to 770 ng U kg-1 urine and with 238U/235U isotopic ratios ranging
      from 138 (100% NU) to 215 (51% DU). Sets of samples were shipped to five testing
      laboratories (four based in Canada and one based in Europe). Each laboratory
      utilized one of the following analytical techniques: sector field inductively
      coupled plasma mass spectrometry (ICP-SF-MS), quadrupole inductively coupled
      plasma mass spectrometry (ICP-Q-MS), thermal ionization mass spectrometry (TIMS),
      and instrumental/delayed neutron activation analysis (I/DNAA), in their analyses.

PMID- 16607187
TI  - Occupational exposure to pesticides and pregnancy outcomes in gardeners and
      farmers: a study within the Danish National Birth Cohort.
AB  - OBJECTIVE: We conducted a follow-up study to examine whether exposure to
      pesticides during pregnancy had an adverse effect on pregnancy outcomes among
      Danish gardeners and farmers. METHODS: Using data from the National Birth Cohort
      in Denmark, we identified 226 pregnancies of gardeners and 214 pregnancies of
      farmers during 1997 through 2003. Work activities and exposure to pesticides were
      reported in an interview (around 16 weeks of gestation). Totally, 62,164 other
      workers in the cohort served as a reference group. Pregnancy outcomes were
      obtained by linkage to the national registers. Cox regression was applied to
      analyze late fetal loss and congenital malformations, and logistic regression was
      used to analyze preterm birth and small for gestational age. RESULTS: There were
      no significant differences in the studied pregnancy outcomes between gardeners or
      farmers and all other workers, except for an increased risk of very preterm birth
      for gardeners and a favorable birth weight for farmers. With the exception of
      biologic approach used in gardening, neither work activities nor exposure to
      pesticides showed a significant increased risk of adverse birth outcomes among
      gardeners or farmers. CONCLUSIONS: Our data suggest little effect of occupational
      exposures to pesticides on pregnancy outcomes among gardeners or farmers in
      Denmark. The results may not apply to other countries.

PMID- 16607188
TI  - pH increase observed in exhaled breath condensate from welding fume exposure.
AB  - OBJECTIVES: We sought to investigate changes in exhaled breath condensate (EBC)
      pH in healthy workers exposed to welding fumes. METHODS: Fourteen exposed
      participants (median age 39 years, 5 smokers) and 8 nonexposed controls (median
      age 44 years, 1 smoker) were monitored at an apprentice welding school. Exposure
      to fine particulate matter less than 2.5 microm (PM2.5) was assessed using
      cyclone samplers. EBC samples were collected at baseline and at the end of the
      work shift. EBC samples were deaerated using argon and pH values were measured
      using standard pH microelectrodes. RESULTS: Mean +/- SEM PM2.5 levels were 1.17
      +/- 0.18 mg/m for exposed subjects and 0.03 +/- 0.01 mg/m for controls. Baseline
      median (range) EBC pH values for the control and exposed group were similar (P =
      0.86), 7.21 (4.91 to 8.26), and 7.39 (4.85 to 7.79), respectively. The exposed
      subjects had a small-but-marginally significant (P = 0.07) pre- to post-work
      shift increase in pH of 0.28, whereas the control group showed a minimal increase
      of only 0.03 (P = 0.56). Compared with the control group, the exposed group had a
      median cross-shift pH increase of 0.25 (P = 0.49). CONCLUSIONS: The aerosolized
      fine particulate matter contained in metal fumes may be associated with an acute
      increase in EBC pH values. Further study is necessary to investigate the acute
      rise in EBC pH after acute exposure to welding fume.

PMID- 16607189
TI  - How much work-related injury and illness is missed by the current national
      surveillance system?
AB  - OBJECTIVE: We sought to estimate the undercount in the existing national
      surveillance system of occupational injuries and illnesses. METHODS: Adhering to
      the strict confidentiality rules of the U.S. Bureau of Labor Statistics, we
      matched the companies and individuals who reported work-related injuries and
      illnesses to the Bureau in 1999, 2000, and 2001 in Michigan with companies and
      individuals reported in four other Michigan data bases, workers' compensation,
      OSHA Annual Survey, OSHA Integrated Management Information System, and the
      Occupational Disease Report. We performed capture-recapture analysis to estimate
      the number of cases missed by the combined systems. RESULTS: We calculated that
      the current national surveillance system did not include 61% and with capture
      recapture analysis up to 68% of the work-related injuries and illnesses that
      occurred annually in Michigan. This was true for injuries alone, 60% and 67%, and
      illnesses alone 66% and 69%, respectively. CONCLUSIONS: The current national
      system for work-related injuries and illnesses markedly underestimates the
      magnitude of these conditions. A more comprehensive system, such as the one
      developed for traumatic workplace fatalities, that is not solely dependent on
      employer based data sources is needed to better guide decision-making and
      evaluation of public health programs to reduce work-related conditions.

PMID- 16607190
TI  - Training pathways for occupational medicine.
AB  - OBJECTIVE: Consider the funding, organization, and applicant pool for
      occupational medicine residency training positions concerns in the United States.
      METHODS: Postgraduate training models are compared for responsiveness to
      competence and workforce needs, including traditional residency, nontraditional
      residency, postdoctoral fellowship, extended courses, multiple certificate
      preparation, continuing medical education, "executive MPH," and implicit
      education (learning from consultants in the course of practice). RESULTS:
      Educational models differ in comprehensiveness, crossdisciplinary experience,
      socialization to core professional values, financial requirements, accessibility
      to physicians currently in practice, potential number of trainees, and short- and
      long-term impact on training outcomes. CONCLUSION: There are tradeoffs between
      the benefits of comprehensive program standards and the benefit of facilitated
      training access by reducing barriers or requirements. Recognizing and
      understanding assumptions about training in our discipline may inform future
      choices.

PMID- 16607191
TI  - Lung cancer development in primary smelter workers: a nested case-referent study.
AB  - OBJECTIVE: The objective of this study was to study the impact of work-related
      exposure to mainly arsenic and lead versus smoking in primary smelter workers
      developing lung cancer. METHODS: In a cohort of 3979 primary smelter workers, 46
      subjects had contracted respiratory malignancies. They were compared with 141 age
      matched male referents by conditional logistic regression analysis. RESULTS:
      Cases showed a significantly higher smoking rate as compared with referents: odds
      ratio (OR) = 4.0; 95% confidence interval (CI) = 1.6-10.1; P = 0.003. When
      restricted to smokers (33 cases, 63 referents), the cumulative air arsenic
      exposure index, but not the lead exposure indices, was significantly higher among
      the cases: OR = 1.07; 95% CI = 1.02-1.11; P = 0.005. CONCLUSIONS: Cumulative
      arsenic exposure and smoking were identified as risk factors for the development
      of lung cancer; lead exposure, however, was not.

PMID- 16607192
TI  - Further development and validation of the Occupational Fatigue Exhaustion
      Recovery (OFER) scale.
AB  - OBJECTIVE: Refinement of the Occupational Fatigue Exhaustion Recovery (OFER)
      scale. METHOD: The responses of 510 nurses to the OFER scale, two of whose scales
      contained additional items, were examined with CFA and regression analyses.
      RESULTS: Analyses of the expanded pool of items identified three subscales of 5
      items each for the renamed OFER15 scale. The subscales have high internal
      reliability (>.84), face, construct and discriminant validity. SEM analysis
      confirmed the role of recovery in mediating the relationship between acute and
      chronic fatigue measured with the OFER15 scale. SIGNIFICANCE: The OFER15 measure
      is a parsimonious scale with robust psychometric properties whose subscales
      distinguish well between acute fatigue states and chronic fatigue traits. The
      intershift recovery subscale is unique among published fatigue scales. The OFER15
      is suggested as a valuable new instrument for the researchers in the work-related
      fatigue area, and also as screening instrument in Primary Care.

PMID- 16607193
TI  - Occupational sun exposure and mycosis fungoides: a European multicenter case
      control study.
AB  - OBJECTIVE: We sought to study the association between occupational sun exposure
      and mycosis fungoides (MF), a peripheral T-cell lymphoma. SUBJECTS AND METHODS: A
      European multicenter case-control study including seven rare cases (one being MF)
      was conducted between 1995 and 1997. From the 118 accepted cases, 104 were
      interviewed, of which 76 were definite cases. Population controls were selected
      randomly from the regions of case ascertainment. Information based on
      occupational experiences was coded according to industry types. A job exposure
      matrix was created according to the expected exposure to sunlight. RESULTS: Once
      exposures to aromatic halogenated hydrocarbons were eliminated (odds ratio = 2.3;
      95% confidence interval = 0.9-6.2), a high MF risk was associated with exposures
      to solar radiation. CONCLUSION: It would appear that workers exposed to sunlight
      have a higher risk of MF. However, this factor is not the only one involved.

PMID- 16607194
TI  - Electrocardiographic abnormality for workers exposed to carbon disulfide at a
      viscose rayon plant.
AB  - OBJECTIVE: This study investigated electrocardiography (ECG) manifestations for
      male workers with carbon disulfide exposure at rayon manufacturing plants.
      METHODS: A total of 251 men in the exposure group and 226 administrative clerks
      in the reference group received physical examinations and completed
      questionnaires. RESULTS: The prevalence of ECG abnormalities was much higher in
      the carbon disulfide exposure group (25.9%, n = 65) than in the reference group
      (2.7%, n = 6), with an odds ratio (OR) of 12.8 (95% confidence interval [CI] =
      5.4-30.2). The foremen were at the highest risk of abnormal ECG (OR = 20.6, 95%
      CI = 6.5-65.2), followed by filament-spinning workers (OR = 14.2, 95% CI = 5.7
      35.3), viscose-manufacturing workers (OR = 11.3, 95% CI = 4.3-30.1), and carbon
      disulfide-manufacturing workers (OR = 8.1, 95% CI = 2.7-25.6). The multivariate
      logistic regression analysis based on cumulative exposure index also showed a
      dose-response relationship with the exposure, and the risk of ECG abnormality
      could be initiated at the exposure history of 31 to 57 year-ppm with an OR of 7.2
      (95% CI = 1.5-36.7). CONCLUSIONS: In general, the ECG abnormalities observed in
      workers at the permissible exposure level of carbon disulfide implicate the
      importance of environmental control of the chemical and of workers' education in
      exposure prevention at work.

PMID- 16607195
TI  - Case-by-case assessment of adult-onset asthma attributable to occupational
      exposures among members of a health maintenance organization.
AB  - OBJECTIVE: In a general population of employed persons with health insurance,
      what proportion of adult-onset asthma is caused by occupational exposures?
      METHOD: We conducted a 2-year prospective study to identify adult-onset asthma
      among health maintenance organization (HMO) members. Telephone interviews
      regarding occupational exposures, symptoms, medication use, and triggers were
      used to assess likelihood of work-related asthma for each case. Weighted
      estimating equations were used to adjust the proportion of asthma attributable to
      workplace exposures for factors associated with interview participation. RESULTS:
      Overall, 29% (95% confidence interval, 25-34%) of adult-onset asthma was
      attributable to workplace exposures; 26% (21-30%) and 22% (18-27%) of cases had
      asthma attributable to occupational irritant and sensitizer exposures,
      respectively. CONCLUSIONS: Occupational exposures, including irritants, are
      important causes of adult-onset asthma.

PMID- 16607196
TI  - Agent Orange, dioxins, and other chemicals of concern in Vietnam: update 2006.
AB  - OBJECTIVE: The objective of this study was to find sites in Vietnam where there
      was human exposure from Agent Orange herbicide sprayed between 1962 and 1971, as
      determined by congener-specific measurement of dioxins, including 2,3,7,8
      tetrachlorodibenzodioxin (TCDD), the dioxin that contaminated Agent Orange, in
      blood. METHODS: Blood was collected from residents of eight heavily sprayed
      regions in the south of Vietnam and analyzed for TCDD and in some cases the
      dioxin-like dibenzofurans and dioxin-like PCBs. RESULTS: Six of the eight newly
      studied sites did not show substantial or any elevated TCDD in blood. Marked
      elevation of TCDD in Vietnamese blood was found in one new location with a
      suggestion of slightly elevated TCDD in a second location. CONCLUSIONS: In newly
      studied locations in Vietnam, we found some persons with elevation of TCDD
      consistent with exposure to dioxin from Agent Orange. In our previous studies, we
      found PCBs, PCDDs, and PCDFs as well as pesticides in human milk, blood, or in
      food. Health effects from Agent Orange need to be differentiated from effects
      caused by chemicals other than TCDD from Agent Orange.

PMID- 16607197
TI  - NC-stat as a screening tool for carpal tunnel syndrome in industrial workers.
AB  - OBJECTIVE: The initial purpose of this study was to establish a normal data set
      for median nerve studies in industrial workers using NC-stat technology. METHODS:
      Sixteen hundred ninety-five persons applying for employment at a single heavy
      industry plant without symptoms of carpal tunnel syndrome (CTS) were studied.
      RESULTS: Values for median distal motor latency (DML), amplitude, and F-waves
      were recorded in the dominant limbs. The DML was 3.81 +/- 0.57 milliseconds, with
      a 95% cut-off value of 4.75 milliseconds. Amplitude of the compound muscle action
      potential was 0.95 +/- 0.46 mV, reflecting the use of volume conduction by this
      technology. Most of the workers who were characterized as having borderline,
      prolonged, or very prolonged distal motor latencies according to NeuroMetrix
      automated report actually fell below the 95% cut-off of this independent data
      analysis. CONCLUSION: NC-stat technology using DML appears to be no more
      sensitive or specific than a traditionally performed DML for the diagnosis of
      CTS. Until recently promoted sensory studies using NC-stat technology are better
      defined, this technology cannot be recommended for screening or diagnosis of CTS
      in an industrial population.

PMID- 16607198
TI  - Differences in workers' compensation disability and impairment ratings under old
      and new California law.
AB  - BACKGROUND: California's workers' compensation law experienced an historic change
      on January 1, 2005. Previous methods used to rate permanent disability were
      replaced by new methods to rate permanent impairment. We sought to estimate the
      difference in ratings under the old and new law. METHODS: We obtained 218 reports
      on injured workers from attorneys who represented injured workers. A disability
      expert rated disability and 15 physicians rated impairment. RESULTS: Average
      percentage point ratings for impairment under the 2005 law were approximately one
      third the size of ratings for disability under the old law. This estimate showed
      little variation across demographic groups, physician-evaluators, or injured body
      part. CONCLUSION: Because cash benefits are keyed to impairment ratings, benefits
      for permanently disabled workers may decrease as much as 60% under the new law.

PMID- 16607199
TI  - Lung cancer mortality in the German chromate industry, 1958 to 1998.
AB  - OBJECTIVES: We conducted a mortality study of two German chromate production
      facilities and evaluated possible dose-response relationships between hexavalent
      chromium exposure and lung cancer. METHODS: Mortality was followed-up through
      1998 and limited to those employed since each plant converted to a no-lime
      production process. More than 12,000 urinalysis results of chromium levels were
      available, as was smoking information. RESULTS: All-cause mortality indicated a
      healthy worker effect (standardized mortality ratio [SMR] = 0.80, 95% confidence
      interval [CI] = 0.67-0.96); however, lung cancers appeared to be increased (SMR =
      1.48, 95% CI = 0.93-2.25). No clear dose-response was found in stratified
      analyses by duration of employment and time since hire. On the basis of urinary
      chromium data, lung cancer risk was elevated only in the highest exposure group
      (SMR = 2.09, 95% CI = 1.08-3.65). CONCLUSIONS: These data suggest a possible
      threshold effect of occupational hexavalent chromium exposure on lung cancer.

PMID- 16607200
TI  - Ethical considerations in testing workers for the -Glu69 marker of genetic
      susceptibility to chronic beryllium disease.
AB  - OBJECTIVE: The most compelling real-world example of genetic testing for
      susceptibility to a workplace exposure involves those industries that process or
      fabricate beryllium. We examined ethical issues associated with testing for
      susceptibility to chronic beryllium disease. METHODS: Using ethical and clinical
      criteria, we examined voluntary employer-sponsored testing programs in which
      individual results are reported directly to workers in a confidential manner.
      RESULTS: Under reasonable assumptions, the longitudinal positive predictive value
      of the HLA-DPB1-Glu69 marker of susceptibility to beryllium disease is 12%.
      Interpretive challenges further limit the utility of the test and may
      inadvertently suggest a false sense of safety among workers. Concerns about
      confidential participation and pressures to be tested also must be addressed.
      CONCLUSIONS: Difficulties surrounding the interpretation of the HLA-DPB1-Glu69
      marker, lack of assurance regarding the protection of worker confidentiality, and
      the potential lowering of social barriers to the implementation of mandatory
      worker screening combine to make testing beryllium workers inappropriate at this
      time.

PMID- 16607203
TI  - Making time for professional development.

PMID- 16607205
TI  - A lesson in the passage of laws.

PMID- 16607204
TI  - A case of acute drug-induced hepatitis.

PMID- 16607206
TI  - Dispensing pharmaceutical samples: a few reminders.

PMID- 16607207
TI  - Treatment strategies for low back pain relief.

PMID- 16607209
TI  - A physical activity Rx for the hypertensive patient.

PMID- 16607211
TI  - Counsel your patients about contraceptive options.

PMID- 16607212
TI  - When a headache is really a brain tumor.

PMID- 16607213
TI  - Ramelteon (rozerem) a novel approach for insomnia treatment.

PMID- 16607218
TI  - Guide to care for patients. Back pain.

PMID- 16607229
TI  - Continuous nebulized albuterol attenuates acute lung injury in an ovine model of
      combined burn and smoke inhalation.
AB  - OBJECTIVE: Albuterol, due to its bronchodilatory and anti-inflammatory effects,
      is given via continuous nebulization in children with severe asthma. Combined
      burn and smoke inhalation injury frequently results in acute lung injury due to a
      combination of airway obstruction and inflammation. We hypothesized that
      albuterol administered via continuous nebulization would mitigate acute lung
      injury after smoke inhalation injury and burn. DESIGN: Randomized prospective
      animal model. SUBJECTS: Twenty adult female sheep (mean weight, 33.1+/-0.9 kg).
      INTERVENTIONS: Adult ewes were subjected to a 40% body surface area third-degree
      flame burn and smoke inhalation injury after tracheostomy. Sheep were allocated
      to a) sham group, b) saline continuous nebulization group, c) 20 mg of albuterol
      continuous nebulization group, or d) 40 mg of albuterol continuous nebulization
      group (n=5 animals per group). All groups received intravenous lactated Ringer's
      solution at 4 mL.kg-1.%burn(-1).24 hrs-1 for resuscitation and were equally
      mechanically ventilated throughout the 48-hr study period. Pulmonary and cardiac
      function, lung lymph flow, bronchial obstruction score, and wet/dry lung weights
      were recorded. RESULTS: Compared with saline and control groups, the albuterol
      groups had lower pause and peak inspiratory pressures, decreased pulmonary
      transvascular fluid flux, a significantly higher Pao2/Fio2 ratio, and decreased
      shunt fraction at 48 hrs postinjury. The wet-to-dry lung weight ratio and
      bronchial obstruction scores were lower for sheep receiving albuterol.
      CONCLUSIONS: Continuous nebulization of albuterol improves pulmonary function via
      improved airway clearance and decreased fluid flux in a combined burn/smoke
      inhalation injury model.

PMID- 16607230
TI  - Elevated serum levels of S-100beta protein and neuron-specific enolase are
      associated with brain injury in patients with severe sepsis and septic shock.
AB  - OBJECTIVE: We investigated whether serum levels of neuron-specific enolase (NSE)
      and S-100beta protein could be used to evaluate cerebral injury and to predict
      outcome in severe sepsis and severe septic shock. DESIGN: Prospective study.
      SETTING: University hospital. PATIENTS AND MEASUREMENTS: In 170 consecutively
      enrolled patients with severe sepsis and septic shock, serum S-100beta and NSE
      were measured daily during four consecutive days after intensive care unit
      admission. Admission Glasgow Coma Scale before sedation and daily Sequential
      Organ Failure Assessment scores were recorded in all patients. Acute
      encephalopathy was defined as either a state of agitation, confusion,
      irritability, and convulsions (type A) or characterized by somnolence, stupor,
      and coma (type B) and persistently observed during 72 hrs after withdrawing
      sedation. When clinically indicated, contrast computed tomography or magnetic
      resonance imaging were performed to evaluate brain injury. MAIN RESULTS: S
      100beta and NSE increased in, respectively, 72 (42%) and 90 (53%) patients. High
      biomarker levels were associated with the maximum Sequential Organ Failure
      Assessment scores (p = .001), and the highest values were found in patients who
      died early, within 4 days of inclusion (p = .005). Low consciousness
      encephalopathy type B was more frequently observed in patients with elevated S
      100beta (p = .004). S-100beta levels of >or=4 microg/L were associated with
      severe brain ischemia or hemorrhage, and values of <2 microg/L were found in
      patients with diffuse cerebral embolic infarction lesions. High S-100beta levels
      were associated with higher intensive care unit mortality (p = .04) and
      represented the strongest independent predictor of intensive care unit survival,
      whereas NSE and the Glasgow Coma Scale failed to predict fatal outcome.
      CONCLUSIONS: S-100beta and NSE are frequently increased and associated with brain
      injury in patients with severe sepsis and septic shock. S-100beta levels more
      closely reflected severe encephalopathy and type of brain lesions than NSE and
      the Glasgow Coma Scale.

PMID- 16607232
TI  - Pulmonary artery catheter use is associated with reduced mortality in severely
      injured patients: a National Trauma Data Bank analysis of 53,312 patients.
AB  - OBJECTIVE: To evaluate the association between pulmonary artery catheter (PAC)
      use and mortality in a large cohort of injured patients. We hypothesized that PAC
      use is associated with improved survival in critically injured trauma patients.
      DESIGN: Retrospective database analysis. SETTING: A total of 268 level 1 trauma
      centers from across the United States. PATIENTS: A total of 53,312 patients
      admitted to the intensive care units of the trauma centers participating in the
      National Trauma Data Bank maintained by the American College of Surgeons.
      MEASUREMENTS AND MAIN RESULTS: The National Trauma Data Bank was queried to
      identify patients aged 16-90 yrs with complete data on base deficit, and Injury
      Severity Score (n=53,312). Patients were initially divided into two groups: those
      managed with a PAC (n=1,933) and those managed without a PAC (n=51,379). Chi
      square and Student's t-test analysis were utilized to explore group differences
      in mortality. In a second analysis, groups were stratified by base deficit,
      Injury Severity Score, and age to further explore the influence of injury
      severity on PAC use and mortality. In addition, a logistic regression model was
      developed to assess the relationship between PAC use and mortality after
      adjusting for differences in age, mechanism, injury severity, injury pattern, and
      co-morbidities. Overall, patients managed with a PAC were older (45.8+/-21.3
      yrs), had higher Injury Severity Score (28.4+/-13.5), worse base deficit (-5.2+/
      6.5), and increased mortality (PAC, 29.7%; no PAC, 9.8%; p<.001). However, after
      stratification for injury severity, PAC use was associated with a survival
      benefit in four subgroups of patients. Each of these groups had advanced age or
      increased injury severity. Specifically, patients aged 61-90 yrs, with arrival
      base deficit worse than -11 and Injury Severity Score of 25-75, had a decrease in
      the risk of death with PAC use (odds ratio, 0.33; 95% confidence interval, 0.17
      0.62). Three additional groups had a similar decrease in the risk of death with
      PAC use: odds ratio, 0.60 (95% confidence interval, 0.43-0.83), 0.82 (95%
      confidence interval, 0.44-1.52), and 0.63 (95% confidence interval, 0.40-0.98).
      Logistic regression analysis demonstrated a decreased mortality when a PAC was
      used in the management of patients with the following severe injury
      characteristics: Injury Severity Score of 25-75, base deficit of less than -11,
      or age of 61-90 yrs (odds ratio, 0.593; 95% confidence interval, 0.437-0.805).
      CONCLUSIONS: Trauma patients managed with a PAC are more severely injured and
      have a higher mortality. However, severely injured patients (Injury Severity
      Score, 25-75) who arrive in severe shock, and older patients, have an associated
      survival benefit when managed with a PAC. This is the first study to demonstrate
      a benefit of PAC use in trauma patients.

PMID- 16607231
TI  - Effect of blood transfusion on outcome after major burn injury: a multicenter
      study.
AB  - OBJECTIVE: To delineate blood transfusion practices and outcomes in patients with
      major burn injury. CONTEXT: Patients with major burn injury frequently require
      multiple blood transfusions; however, the effect of blood transfusion after major
      burn injury has had limited study. DESIGN: Multicenter retrospective cohort
      analysis. SETTING: Regional burn centers throughout the United States and Canada.
      PATIENT POPULATION: Patients admitted to a participating burn center from January
      1 through December 31, 2002, with acute burn injuries of >or=20% total body
      surface area. OUTCOMES MEASURED: Outcome measurements included mortality, number
      of infections, length of stay, units of blood transfused in and out of the
      operating room, number of operations, and anticoagulant use. RESULTS: A total of
      21 burn centers contributed data on 666 patients; 79% of patients survived and
      received a mean of 14 units of packed red blood cells during their
      hospitalization. Mortality was related to patient age, total body surface area
      burn, inhalation injury, number of units of blood transfused outside the
      operating room, and total number of transfusions. The number of infections per
      patient increased with each unit of blood transfused (odds ratio, 1.13; p<.001).
      Patients on anticoagulation during hospitalization received more blood than
      patients not on anticoagulation (16.3+/-1.5 vs. 12.3+/-1.5, p<.001). CONCLUSIONS:
      The number of transfusions received was associated with mortality and infectious
      episodes in patients with major burns even after factoring for indices of burn
      severity. The utilization of blood products in the treatment of major burn injury
      should be reserved for patients with a demonstrated physiologic need.

PMID- 16607233
TI  - Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in
      critically ill patients: results of a randomized, double-blind, placebo
      controlled trial.
AB  - OBJECTIVE: To describe the erythropoietin pharmacokinetic profile after once
      weekly epoetin alfa treatment in critically ill patients. Secondary objectives
      were to compare pharmacodynamic and safety profiles between active treatment and
      placebo in these patients. DESIGN: Randomized, double-blind, placebo-controlled
      study. SETTING: Medical, surgical, or mixed medical/surgical intensive care
      units. PATIENTS: A total of 73 anemic critically ill adults with an expected stay
      of >3 days and a hematocrit value of <38%. INTERVENTIONS: Patients were
      randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once
      weekly (n=48) or matching placebo (n=25) for up to 4 wks. MEASUREMENTS AND MAIN
      RESULTS: Serum erythropoietin concentration and hematologic variables (percentage
      reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts)
      were measured, and area under the serum concentration-time curve from time 0 to
      the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0
      Tlast) for these three variables was determined. Mean serum erythropoietin
      concentrations in placebo patients were slightly higher than typical physiologic
      levels of erythropoietin in healthy subjects, although not appropriate for the
      degree of anemia in these patients. Overall, exposure of endogenous
      erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20%
      of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline
      hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in
      hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the
      epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher
      with epoetin alfa than with placebo and was related to the AUC of erythropoietin.
      There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between
      epoetin alfa and placebo groups, which was most likely due to bleeding and
      transfusion events. Epoetin alfa was safe and well tolerated, with a rate of
      treatment-emergent complications similar to that seen with placebo. CONCLUSION:
      Epoetin alfa, once weekly, augmented the erythropoietic response in critically
      ill patients as indicated by the increased erythropoietin levels and larger
      AUC(RETI)0-Tlast in treated patients.

PMID- 16607234
TI  - Critical care of the bariatric patient.
AB  - OBJECTIVE: To synthesize the current literature on care of obese, critically ill,
      and bariatric surgical patients. DATA SOURCE: A MEDLINE/PubMed search from 1966
      to August 2005 was conducted using the search terms obesity, bariatric surgery,
      and critical illness, and a search of the Cochrane Library was also conducted.
      DATA EXTRACTION AND SYNTHESIS: An increase in both the prevalence of obesity and
      the number of bariatric procedures performed has resulted in an increased number
      of obese and, specifically, bariatric surgical patients who require intensive
      care unit care. Obesity is a chronic inflammatory state with resultant effects on
      immune, metabolic, respiratory, cardiovascular, gastrointestinal, hematologic,
      and renal function. Principles of care of the critically ill obese patient are
      reviewed and then applied to critically ill bariatric surgical patients.
      Pharmacotherapy, vascular access, and the presentation and management of both
      pressure-induced rhabdomyolysis and anastomotic failure after bariatric surgery
      are also reviewed. CONCLUSIONS: Obesity causes a range of pathologic effects on
      all major organ systems. Knowledge of these effects and issues specific to the
      intensive care unit care of bariatric patients can help to predict and manage
      complications in this population.

PMID- 16607235
TI  - Morbidity and mortality risk associated with red blood cell and blood-component
      transfusion in isolated coronary artery bypass grafting.
AB  - OBJECTIVE: Our objective was to quantify incremental risk associated with
      transfusion of packed red blood cells and other blood components on morbidity
      after coronary artery bypass grafting. DESIGN: The study design was an
      observational cohort study. SETTING: This investigation took place at a large
      tertiary care referral center. PATIENTS: A total of 11,963 patients who underwent
      isolated coronary artery bypass from January 1, 1995, through July 1, 2002.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 11,963 patients who
      underwent isolated coronary artery bypass grafting, 5,814 (48.6%) were
      transfused. Risk-adjusted probability of developing in-hospital mortality and
      morbidity as a function of red blood cell and blood-component transfusion was
      modeled using logistic regression. Transfusion of red blood cells was associated
      with a risk-adjusted increased risk for every postoperative morbid event:
      mortality (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.67-1.87;
      p<.0001), renal failure (OR, 2.06; 95% CI, 1.87-2.27; p<.0001), prolonged
      ventilatory support (OR, 1.79; 95% CI, 1.72-1.86; p<.0001), serious infection
      (OR, 1.76; 95% CI, 1.68-1.84; p<.0001), cardiac complications (OR, 1.55; 95% CI,
      1.47-1.63; p<.0001), and neurologic events (OR, 1.37; 95% CI, 1.30-1.44;
      p<.0001). CONCLUSIONS: Perioperative red blood cell transfusion is the single
      factor most reliably associated with increased risk of postoperative morbid
      events after isolated coronary artery bypass grafting. Each unit of red cells
      transfused is associated with incrementally increased risk for adverse outcome.

PMID- 16607236
TI  - Activated partial thromboplastin time waveform analysis: a new tool to detect
      infection?
AB  - OBJECTIVE: An abnormality of the optical transmission waveform obtained during
      measurement of the activated partial thromboplastin time (aPTT) has been
      described to identify a high-risk intensive care unit population consisting of
      patients with sepsis or with higher mortality rates than patients with normal
      aPTT waveforms. We investigated the abnormal aPTT biphasic waveform as a
      diagnostic and prognostic marker of infection. DESIGN: Prospective, observational
      study investigating the predictive value of aPTT waveform analysis for the
      diagnosis and prognosis of sepsis. SETTING: Surgical intensive care unit of a
      university hospital. PATIENTS: We studied 187 consecutive patients who fulfilled
      at least two or more criteria of the systemic inflammatory response syndrome at
      admission or during intensive care stay and classified as having systemic
      inflammatory response syndrome, sepsis, severe sepsis, or septic shock during an
      8-month period. INTERVENTIONS: Laboratory analyses including aPTT waveform
      analysis and procalcitonin and C-reactive protein concentrations were measured at
      days 1-3. MEASUREMENTS AND MAIN RESULTS: The final diagnoses were systemic
      inflammatory response syndrome in 49%, sepsis in 16%, severe sepsis in 12%, and
      septic shock in 23% of patients. On day 1, the biphasic waveform was
      significantly more abnormal in patients with severe sepsis or septic shock than
      in patients with systemic inflammatory response syndrome or sepsis. The biphasic
      waveform was more accurate than procalcitonin and C-reactive protein for
      differentiating patients with severe sepsis and septic shock, with 90%
      sensitivity and 92% negative predictive value. Biphasic waveform values were
      significantly more abnormal during days 1-3 in septic nonsurvivors than in
      survivors and nonseptic nonsurvivors. The biphasic waveform exhibited the best
      specificity (91%) and negative predictive value (98%) for the prognosis of sepsis
      related mortality on day 3. CONCLUSIONS: In intensive care units, when the
      analyzer is available, aPTT waveform analysis is an inexpensive, rapid,
      effective, and readily available tool providing information for the diagnosis of
      severe sepsis and the prognosis of septic patients.

PMID- 16607237
TI  - Using case reports to aid reflective practice in wound care.
AB  - Reflection is a widely-used tool in education and practice for giving individuals
      insight into events and incidents. Case reports, though lacking in rigour as a
      source of evidence, also provide an opportunity to reflect on and examine
      practice. They therefore provide a useful opportunity of examining practice in
      wound care, which is lacking in many nursing curricula. A case report is given
      here to illustrate some of the lessons that can be learned by reflection--even by
      an experienced nurse.

PMID- 16607238
TI  - Skin cooling, pain and chronic wound healing progression.
AB  - There are many areas of wound care where theory does not always match the
      practical experiences of the patient. This article discusses the effects of two
      factors--skin cooling and pain--on chronic wound healing, and the role of pain
      and inflammation on the overall wound healing process.

PMID- 16607239
TI  - Static magnets prevent leg ulcer recurrence: savings for the NHS?
AB  - The objectives of this survey were to examine the effectiveness of a static
      magnet device--4UlcerCare--in preventing recurrence of leg ulcers after healing.
      Two hundred and eighty-nine randomly selected purchasers of 4UlcerCare were
      telephoned and asked to complete a short questionnaire. Our focus was on the 211
      respondents who had ulcers that had already healed. The average age of subjects
      was 70.6 years and sex distribution was 55% female to 45% male. Mean duration of
      leg ulcers before using 4UlcerCare was 4.4 years. Sixty-five per cent of those
      surveyed had had ulcer recurrence before using 4UlcerCare, with a mean of 2.41
      episodes of ulceration. This was close to the expected recurrence rate in the
      population of 67%. Using 4UlcerCare daily, these respondents' ulcers had healed
      within an average of 3.57 months. The survey took place an average of 19.94
      months after healing. The manufacturers advise wearing 4UlcerCare daily post
      healing, and of those respondents that had, none had suffered any recurrence.
      Extrapolating these results across the health economy, an estimate has been made
      of a potential pound153.7 million per year saving on leg ulcer care to the NHS.

PMID- 16607240
TI  - Wound care education needs a boost.

PMID- 16607241
TI  - Avoiding allergic contact dermatitis in patients with venous leg ulcers.
AB  - The management of venous leg ulcers is frequently problematic, usually as a
      result of the patient's existing co-morbidities, but often because of problems in
      skin management, such as hyperkeratosis or skin sensitization and resulting
      contact dermatitis. Good leg ulcer management practice includes skin care,
      protection from excessive exudate and from potential sensitisers. This article
      explores how the practitioner can recognize allergic contact dermatitis in a
      patient with a venous leg ulcer and avoid the use of avoid potential skin
      sensitizers during management.

PMID- 16607243
TI  - Putting policy into practice: the example of COPD.
AB  - Chronic lung disease is one of the commonest reasons for consulting a health
      professional, and there may be as many as 3 million people in the UK with
      undiagnosed chronic obstructive pulmonary disease (COPD). This fourth article in
      a series on long-term conditions examines the policy developments that have been
      put in place to manage the burden of chronic disease in England and Wales, and
      argues that more remains to be done if COPD is to be properly addressed.

PMID- 16607244
TI  - District nurses' triggers for referral of patients to the Macmillan nurse.
AB  - This study aimed to identify the triggers which motivate district nurses to refer
      patients to the Macmillan nursing service and resulted from observation within
      the researcher's clinical practice, when it was noted that referral patterns from
      district nurses to the Macmillan nursing service were very inconsistent. A
      qualitative exploratory descriptive design was utilised and the analysis of the
      findings identified three 'key' themes, which motivate district nurses to refer:
      knowledge and skills, interprofessional issues and perception of Macmillan.
      Within each theme emerged an amalgam of triggers which were complex in nature,
      pertaining not only to patient need, but also to the needs of the district
      nursing service. However, it became apparent during the analysis that there was
      also a lack of knowledge regarding the role of the Macmillan nurse. This lack of
      knowledge relating to the Macmillan nurse role had been affirmed previously by
      several authors (Graves and Nash 1993, Clark et al 2002, Ahmed et al 2004) but
      the literature also reported that the Macmillan nurse role was open to confusion
      (Clark et al 2002, Corner 2003). This confusion may potentially affect referrals
      and prevent patients from receiving the services of the Macmillan nurse. This
      study has established a need for the development of referral criteria into the
      Macmillan nursing service and that there is also an identified need for further
      research, providing scope for the Macmillan nurse and district nurse to work
      collaboratively to improve palliative services in the community.

PMID- 16607245
TI  - Supporting older people: death and bereavement.
AB  - In this article, brought to you in association with Help the Aged, Jonathan Ellis
      discusses the important role nurses can play in helping older people at the end
      of their lives, and calls for better training.

PMID- 16607246
TI  - Catheter valves for indwelling urinary catheters: a systematic review.
AB  - This mini-review aimed to systematically review the evidence on the effect of
      catheter valves compared to free drainage into a bag for patients with indwelling
      urinary catheters. Data sources used were Medline, British Nursing Index, CINAHL,
      Ahmed, EMBASE, EBM Reviews, the Cochrane Library and reference lists of relevant
      papers. Papers considered were controlled trials comparing the use of a catheter
      valve with the catheter bag that were published as a full report, or detailed
      abstract (containing sufficient information to critique) in Dutch, German or
      English. Two studies with a total of 122 subjects were identified. The main
      outcome measures considered were reduction of incidence of bladder spasm and
      urinary tract infection (UTI) and patient preference. No statistically difference
      in the incidence of bladder spasm or UTI was demonstrated but patients showed a
      clear preference for the valve. Further research into catheter valves is needed,
      with larger study groups, which include housebound male and female patients, and
      longer follow-up period.

PMID- 16607247
TI  - Empowerment in nursing homes: lessons for district nursing?
AB  - Empowerment in nursing homes is seldom discussed, although patient empowerment is
      a key policy objective in many countries. This study explored strategies nurses
      in nursing homes and district nursing may use in order to empower themselves and
      the nursing home residents. Fourteen nurses from three nursing homes in Norway
      were observed and interviewed. The main finding was that the nurses where
      striving for the best outcome for the residents, and used strategies including
      negotiation and raising awareness to empower residents and each other.

PMID- 16607248
TI  - Making decisions for incapable adults 1: Capacity and best interest.
AB  - The Mental Capacity Act 2005 is expected to come into force in April 2007. It
      will change the way decisions are made for incapable adults in England and Wales.
      District nurses, along with other health professionals, will be required to abide
      by the provisions of the Act when providing care and treatment to incapable
      adults. In a short series of articles, case studies will be used to illustrate
      how the new law will affect district nurse practice, beginning with the
      assessment of capacity and best interests. District nurse Mary Holt regularly
      visits a patient, 78-year-old Jane Harris, in her home to treat a chronic leg
      ulcer. Jane has been diagnosed with Alzheimer's dementia but is managing well
      with support from the local authority. However, Mary has noticed recently that
      Jane's behaviour has become a little strange. She looks unkempt and she is
      continually washing dishes that are not dirty. On her last visit, Jane refused to
      allow Mary to remove the dressing on her leg and treat the ulcer, which has
      become infected. Mary is concerned that Jane's wound needs to be treated to
      prevent further complications.

PMID- 16607249
TI  - A new direction for community services?

PMID- 16607250
TI  - The best health care possible, at least for now.

PMID- 16607251
TI  - Paying the price: health care and prostitution.

PMID- 16607252
TI  - Smoke-free hospitals and the role of smoking cessation services.
AB  - The NHS must be smoke free by the end of 2006 (Department of Health, 2004). The
      necessary elements to introducing a smoke-free policy, which is workable and
      equitable, are the management of the policy and offering support to smokers.
      Smoking and second-hand smoking are responsible for many illnesses, premature
      deaths and reduced productivity. Employers have a responsibility to ensure the
      health of their employees by protecting them from exposure to cigarette smoke in
      the workplace. Although smoking restrictions in the workplace are popular, it is
      important to ensure good communication with everyone who will be affected, since
      there are many fears associated with the introduction of the policy. Help must be
      offered to people who wish to quit through behavioural and pharmacological
      interventions and support must also be given to the smoker who must abstain from
      smoking on the premises during work or hospital stay.

PMID- 16607253
TI  - What is effective intervention?--using theories of health promotion.
AB  - The increased prevalence of chronic disease offers nurses the challenge of
      providing educational interventions for people living and managing a condition
      such as diabetes mellitus. This article uses theoretical models and approaches
      from health promotion to offer perspectives to explain behaviour and determinants
      of health. The competing needs and perspectives are applied to see their
      relevance within diabetes nursing care, and in particular when looking at patient
      outcomes for a group intervention, raising the question: what is an effective
      intervention? Evaluating interventions needs clear identifiable values and aims,
      although this article highlights that success of any intervention will mean
      different things for the participant or health professional. There is a need for
      research into the subjective experiences of people with diabetes managing an
      intensive insulin regimen, and to value and include a wider definition of
      evidence-based outcomes.

PMID- 16607254
TI  - Clinical Corner: Management of pyrexia during blood transfusion.

PMID- 16607255
TI  - Nursing management of the patient with Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive, degenerative, debilitating illness
      that affects all races and both sexes. In 2002 the numbers of women over the age
      of 90 years with AD were higher compared with men of the same age group (Office
      for National Statistics (ONS), 2004). Although there are no data identifying the
      number of women suffering from AD compared with men, it could be concluded from
      these data (ONS, 2004) that more women than men suffer from AD. The number of
      individuals suffering from AD is increasing as people are living longer. Analysis
      of postmortem brain tissue in patients with AD has identified senile plaques in
      the hippocampal region, neurofibrillary tangles in the brain cells and also a
      decline in levels of acetylcholine in the brain. There is no known cure for the
      illness and therefore patients will ultimately require constant care in the
      community or in special units in residential homes. The National Service
      Framework for Long-Term Conditions (Department of Health, 2005) gives clear
      guidelines for healthcare providers in caring for these patients.

PMID- 16607256
TI  - What information patients require on graduated compression stockings.
AB  - Graduated compression stockings are used prophylactically on a variety of
      patients within acute hospitals. Anecdotal evidence suggests patients have a
      limited understanding of this treatment. The aim of this qualitative study was to
      explore patients' experiences of compression stockings and to ascertain
      perceptions of their use. Information was gathered using telephone interviews
      from a sample of 12 adults who had been patients within the past 2 months, and
      who had worn compression stockings for more than 48 hours. The results showed
      that patients received little or no information from healthcare staff regarding
      compression stockings, but that they did have knowledge from other sources, such
      as long-haul flight advice. This raises issues of informed consent and patient
      empowerment and highlights the need for both verbal and written information. The
      information gained informed a patient information leaflet, which was developed in
      partnership with a patient focus group.

PMID- 16607257
TI  - Leg ulcers.
AB  - This article considers the law which applies to the standard of care when
      patients are being treated in the community for persistent ulcers. It considers
      the importance of expert opinion in determining the reasonable standard of care
      and the significance of the guidelines of the National Institute for Health and
      Clinical Excellence.

PMID- 16607258
TI  - Congenital cardiac malformations in relation to central venous access.
AB  - During the third and seventh weeks of gestation, teratogenic exposure may lead to
      fetal abnormality such as congenital heart defects or intrauterine death.
      Congenital heart defects are present from birth, but may appear at any time, or
      only revealed postmortem. Often defects are present by degree. Some defects are
      life-threatening, while other, less severe conditions, may have minimal
      physiological impact. Left superior vena cava exists in early embryonic
      development, but the vessel degenerates as the cardiovascular system matures.
      When not associated with other malformations, an incidence of persistent left
      sided superior vena cava (PLSVC) has no clinical signs or symptoms. However, it
      may not be as innocuous as it appears due to its association with the cyanotic
      defect, tetralogy of Fallot (TOF). Using a case history as an illustration it can
      be shown that all cases of defect or chromosomal suspicion should be documented
      as there may be implications for future interventions.

PMID- 16607259
TI  - Detachable functional focused rigidity cast for metatarsal fractures.
AB  - This article aims to assess whether a detachable functional focused rigidity cast
      can be used as a one-off definitive treatment for proximal 5th metatarsal
      fractures. A prospective trial was carried out over a 2-year period. Forty-one
      patients with proximal 5th metatarsal fractures (tuberosity and Jones) were
      recruited and treated with a detachable focused rigidity cast after appropriate
      consent. Of the 39 patients with follow-up, six had a Jones fracture and 33 had
      tuberosity fractures. All 33 patients with tuberosity fractures achieved clinical
      union within 4-5 weeks (mean of 4.2 weeks). Four of the six patients with Jones
      fractures achieved clinical union in 8-12 weeks. One achieved union in 14 weeks
      and one underwent open reduction and internal fixation for delayed union. There
      were no complications related to the cast. The results support the use of a
      detachable focused rigidity cast as a one-off definitive treatment of tuberosity
      fractures of the 5th metatarsal. However, all the Jones fractures and the
      diaphyseal fractures should be referred to an orthopaedic team for further
      management.

PMID- 16607260
TI  - The importance of measuring and recording vital signs correctly.

PMID- 16607261
TI  - Funding decisions in chronically sick individuals.
AB  - This article examines current research, literature and government policy that
      influences how health funding is allocated for treatment and care of the
      chronically sick. Chronic disease represents a huge burden of ill health in the
      UK and a substantial cost to the NHS. With both an increase in the ageing
      population and advancing technological developments giving doctors the
      theoretical ability to sustain the most fragile life, the issue of providing
      unlimited access of care to the chronically sick within financial limitations is
      clearly untenable. This article explores the issue of funding the needs of the
      chronically sick while posing a significant challenge both politically and
      financially to the healthcare system. It examines the controversial policies of
      rationing implemented by various governments since the conception of the NHS.
      Some have proved unworkable, all have been controversial, and still the challenge
      remains to provide a comprehensive care package with limited resources. The issue
      of how to ration resources to the chronically sick remains unresolved. Social
      gerontologists predict that living to 120 years of age may become the norm before
      the end of this century. Exploitation of the genome map and society's
      unwillingness to accept the inevitability of disability resulting from chronic
      illness will further increase pressure on healthcare financing and, as a result,
      demands will be forever increasing despite the most rigorous attempts at
      rationing.

PMID- 16607262
TI  - How old is too old (or too young) to resuscitate?

PMID- 16607263
TI  - Cloning MIT.

PMID- 16607264
TI  - Shoichiro Tsukita 1953-2005.

PMID- 16607265
TI  - Deubiquitinating PCNA: a downside to DNA damage tolerance.

PMID- 16607267
TI  - Chromosomes walk the line.

PMID- 16607266
TI  - Chordin cleavage is sizzling.

PMID- 16607268
TI  - Eisosomes: endocytic portals.

PMID- 16607269
TI  - Opening the door to CO2.

PMID- 16607270
TI  - Oocytes originating from skin?

PMID- 16607271
TI  - Pathways to silencing unite.

PMID- 16607274
TI  - A conditional model of MLL-AF4 B-cell tumourigenesis using invertor technology.
AB  - MLL-AF4 fusion is the most common consequence of chromosomal translocations in
      infant leukaemia and is associated with a poor prognosis. MLL-AF4 is thought to
      be required in haematopoietic stem cells to elicit leukaemia and may be involved
      in tumour phenotype specification as it is only found in B-cell tumours in
      humans. We have employed the invertor conditional technology to create a model of
      MLL-AF4, in which a floxed AF4 cDNA was knocked into Mll in the opposite
      orientation for transcription. Cell-specific Cre expression was used to generate
      Mll-AF4 expression. The mice develop exclusively B-cell lineage neoplasias,
      whether the Cre gene was controlled by B- or T-cell promoters, but of a more
      mature phenotype than normally observed in childhood leukaemia. These findings
      show that the MLL-AF4 fusion protein does not have a mandatory role in multi
      potent haematopoietic stem cells to cause cancer and indicates that MLL-AF4 has
      an instructive function in the phenotype of the tumour.

PMID- 16607275
TI  - Overexpression of the prostaglandin E2 receptor EP2 results in enhanced skin
      tumor development.
AB  - We previously showed that the EP2 knockout mice were resistant to chemically
      induced skin carcinogenesis. The purpose of this study was to investigate the
      role of the overexpression of the EP2 receptor in mouse skin carcinogenesis. To
      determine the effect of overexpression of EP2, we used EP2 transgenic (TG) mice
      and wild-type (WT) mice in a DMBA (7,12-dimethylbenz[alpha]anthracene)/TPA (12-O
      tetradecanoylphorbol-13-acetate) two-stage carcinogenesis protocol. EP2 TG mice
      developed significantly more tumors compared with WT mice. Overexpression of the
      EP2 receptor increased TPA-induced keratinocyte proliferation both in vivo and in
      vitro. In addition, the epidermis of EP2 TG mice 48 h after topical TPA treatment
      was significantly thicker compared to that of WT mice. EP2 TG mice showed
      significantly increased cyclic adenosine monophosphate levels in the epidermis
      after prostaglandin E2 (PGE2) treatment. The inflammatory response to TPA was
      increased in EP2 TG mice, as demonstrated by an increased number of macrophages
      in the dermis. Tumors and 7 x TPA-treated and DMBA-TPA-treated (6 weeks) skins
      from EP2 TG mice produced more blood vessels than those of WT mice as determined
      by CD-31 immunostaining. Vascular endothelial growth factor (VEGF) protein
      expression was significantly increased in squamous cell carcinoma (SCC) samples
      from EP2 TG mice compared that of WT mice. There was, however, no difference in
      the number of apoptotic cells in tumors from WT and EP2 TG mice. Together, our
      results suggest that the overexpression of the EP2 receptor plays a significant
      role in the protumorigenic action of PGE2 in mouse skin.

PMID- 16607276
TI  - ADAM12 is highly expressed in carcinoma-associated stroma and is required for
      mouse prostate tumor progression.
AB  - The interaction between stromal cells and tumor cells is emerging as a critical
      aspect of tumor progression. Yet there is a paucity of molecular markers for
      cells participating in such interactions, and only few genes are known to play a
      critical role in this process. Here, we describe the identification of ADAM12 (a
      disintegrin and metalloprotease 12) as a novel marker for a subpopulation of
      stromal cells that are adjacent to epithelial tumor cells in three mouse
      carcinoma models (models for prostate, breast and colon cancer). Moreover, we
      show that ADAM12 is essential for tumor development and progression in the W10
      mouse model for prostate cancer. These results suggest that ADAM12 might be a
      useful marker for stromal cells in mouse tumors that are likely to participate in
      stromal/tumor cell crosstalk, and that ADAM12 is a potential target for design of
      drugs that prevent carcinoma growth.

PMID- 16607277
TI  - Histone modifications silence the GATA transcription factor genes in ovarian
      cancer.
AB  - Altered expression of GATA factors was found and proposed as the underlying
      mechanism for dedifferentiation in ovarian carcinogenesis. In particular, GATA6
      is lost or excluded from the nucleus in 85% of ovarian tumors and GATA4
      expression is absent in majority of ovarian cancer cell lines. Here, we evaluated
      their DNA and histone epigenetic modifications in five ovarian epithelial and
      carcinoma cell lines (human 'immortalized' ovarian surface epithelium (HIO)-117,
      HIO-114, A2780, SKOV3 and ES2). GATA4 and GATA6 gene silencing was found to
      correlate with hypoacetylation of histones H3 and H4 and loss of histone
      H3/lysine K4 tri-methylation at their promoters in all lines. Conversely, histone
      H3/lysine K9 di-methylation and HP1gamma association were not observed, excluding
      reorganization of GATA genes into heterochromatic structures. The histone
      deacetylase inhibitor trichostatin A, but not the DNA methylation inhibitor 5'
      aza-2'-deoxycytidine, re-established the expression of GATA4 and/or GATA6 in
      A2780 and HIO-114 cells, correlating with increased histone H3 and H4
      acetylation, histone H3 lysine K4 methylation and DNase I sensitivity at the
      promoters. Therefore, altered histone modification of the promoter loci is one
      mechanism responsible for the silencing of GATA transcription factors and the
      subsequent loss of a target gene, the tumor suppressor Disabled-2, in ovarian
      carcinogenesis.

PMID- 16607278
TI  - Aberrant promoter methylation and silencing of the POU2F3 gene in cervical
      cancer.
AB  - POU2F3 (OCT11, Skn-1a) is a keratinocyte-specific POU transcription factor whose
      expression is tied to squamous epithelial stratification. It is also a candidate
      tumor suppressor gene in cervical cancer (CC) because it lies in a critical loss
      of heterozygosity region on 11q23.3 in that cancer, and its expression is lost in
      more than 50% of CC tumors and cell lines. We now report that the loss of POU2F3
      expression is tied to the hypermethylation of CpG islands in the POU2F3 promoter.
      Bisulfite sequencing analysis revealed that methylation of specific CpG sites (
      287 to -70 bp) correlated with POU2F3 expression, which could be reactivated with
      a demethylating agent. Combined bisulfite restriction analysis revealed aberrant
      methylation of the POU2F3 promoter in 18 of 46 (39%) cervical tumors but never in
      normal epithelium. POU2F3 expression was downregulated and inversely correlated
      with promoter hypermethylation in 10 out of 11 CC cell lines. Immunohistochemical
      analysis on a cervical tissue microarray detected POU2F3 protein in the
      epithelium above the basal layer. As the disease progressed, expression also
      decreased, especially in invasive squamous cell cancer (70% loss). Thus, aberrant
      DNA methylation of the CpG island in POU2F3 promoter appears to play a key role
      in silencing this gene expression in human CC. The results suggested that POU2F3
      might be one of the CC-related tumor suppressor genes, which are disrupted by
      both epigenetic and genetic mechanisms.

PMID- 16607279
TI  - Ras-dependent carbon metabolism and transformation in mouse fibroblasts.
AB  - Mutational activation of ras genes is required for the onset and maintenance of
      different malignancies. Here we show, using a combination of molecular
      physiology, nutritional perturbations and transcriptional profiling, that full
      penetrance of phenotypes related to oncogenic Ras activation, including the shift
      of carbon metabolism towards fermentation and upregulation of key cell cycle
      regulators, is dependent upon glucose availability. These responses are induced
      by Ras activation, being specifically reverted by downregulation of the Ras
      pathway obtained through the expression of a dominant-negative Ras-specific
      guanine nucleotide exchange protein. Our data allow to link directly to ras
      activation the alteration in energy metabolism of cancer cells, their fragility
      towards glucose shortage and ensuing apoptotic death.

PMID- 16607280
TI  - A functional link between the tumour suppressors ARF and p33ING1.
AB  - The ARF tumour suppressor protein plays a critical role in the activation of p53
      in response to oncogenic stress. ARF can activate p53 through nucleolar
      sequestration of Mdm2. However, several lines of evidence indicate that this is
      not the only way of action of ARF, and alternative mechanisms must exist. p33ING1
      is a putative tumour suppresor, which induces cell-cycle arrest and apoptosis in
      a p53-dependent manner. Here, we describe that ARF and p33ING1 can interact in
      vivo. We also show that the subcellular localization of ING1 can be modulated by
      ARF protein levels, causing a displacement from nuclear to nucleolar
      localization. Finally, the ability of p33ING1 to cause cell-cycle arrest and
      induction of p21CIP1, or Mdm2, is impaired in ARF-deficient primary mouse
      fibroblasts. Based on these observations, we propose that the interaction with
      p33ING1 represents a novel mechanism for the tumour suppression function of ARF.

PMID- 16607281
TI  - Requirement of nectin, but not cadherin, for formation of claudin-based tight
      junctions in annexin II-knockdown MDCK cells.
AB  - Adherens junctions (AJs) and tight junctions (TJs) comprise a junctional complex
      which plays key roles not only in cell adhesion and polarization but also in
      regulation of cell movement and proliferation in epithelial cells. E-Cadherin and
      nectin are major cell-cell adhesion molecules (CAMs) at AJs, whereas claudin is a
      major CAM at TJs. We have shown that the cadherin-based cell-cell adhesion is not
      formed in MDCK cells in which annexin II, a Ca(2+)- and phospholipid-binding
      protein, is knocked down. Here, we found that TJs and the nectin-based cell-cell
      adhesions were formed in annexin II-knockdown cells. The formation of TJs in
      annexin II-knockdown MDCK cells required the nectin-based cell-cell adhesion and
      afadin, a nectin- and actin-filament-binding protein. In addition, it required
      the activation of Cdc42 and Rac small G proteins and subsequent reorganization of
      the IQGAP1-dependent actin cytoskeleton which were induced by the nectin-based
      cell-cell adhesion. These results indicate that the nectin-based cell-cell
      adhesion and afadin, but not the cadherin-based cell-cell adhesion, are necessary
      for the formation of TJs and that the signaling by nectin and the subsequent
      reorganization of the actin cytoskeleton are also necessary for the formation of
      TJs under certain conditions.

PMID- 16607282
TI  - Deciphering the H-Ras pathway in Xenopus oocyte.
AB  - Xenopus oocytes are arrested in prophase of the first meiotic division. In
      response to progesterone, they re-enter meiosis and arrest again in metaphase of
      the second meiotic division. This process, called meiotic maturation, is under
      the control of the Cyclin B-Cdc2 complex, M phase promoting factor (MPF).
      Injection of a constitutively active Xenopus H-Ras protein activates MPF,
      suggesting that Ras proteins could be implicated in the progesterone transduction
      pathway. The aim of this study was (1) to elucidate the pathway triggered by H
      Ras leading to MPF activation in Xenopus oocytes and (2) to investigate whether
      endogenous H-Ras is involved in the physiological process of meiotic maturation.
      We generated three constitutively active double mutants, each of them recruiting
      a single effector in mammalian cells, mitogen-activated protein kinase (MAPK),
      phosphatidylinositol 3-kinase (PI3K) or RalGDS. Our results show that the
      activation of a PI3K-related enzyme is crucial for H-Ras-induced MPF activation,
      whereas the recruitment of either MAPK or RalGDS is not. However, although the H
      Ras/PI3K pathway is functional in Xenopus oocytes, it is not the physiological
      transducer of progesterone responsible for meiotic resumption.

PMID- 16607283
TI  - 5-Aza-2'-deoxycytidine and IFN-gamma cooperate to sensitize for TRAIL-induced
      apoptosis by upregulating caspase-8.
AB  - Resistance of tumors to cytotoxic therapy remains a major obstacle in cancer
      treatment and is often caused by defects in apoptosis programs. Caspase-8, a key
      mediator of death receptor-induced apoptosis, has previously been reported to be
      frequently inactivated by epigenetic silencing in many tumors, for example in
      neuroblastoma or medulloblastoma. Here, we provide for the first time evidence
      that combined treatment with suboptimal concentrations of the demethylating agent
      5-Aza-2'-deoxycytidine (5-dAzaC) and interferon-gamma (IFN-gamma) cooperated to
      upregulate caspase-8 expression in neuroblastoma and medulloblastoma cells
      lacking caspase-8. Consequently, activation of caspase-8 and downstream caspases
      upon addition of TNF-related apoptosis-inducing ligand (TRAIL) was restored by
      pretreatment with 5-dAzaC and IFN-gamma. Importantly, pretreatment with 5-dAzaC
      and IFN-gamma acted in concert to significantly enhance TRAIL-induced apoptosis
      in neuroblastoma and medulloblastoma cells. Inhibition of caspase-8 by dominant
      negative caspase-8 or by the relatively specific caspase-8 inhibitior zIETD.fmk
      inhibited the increase in apoptosis provided by 5-dAzaC and IFN-gamma, indicating
      that caspase-8 is a key mediator of this sensitization effect. Thus, by
      demonstrating that 5-dAzaC and IFN-gamma at relatively low individual
      concentrations cooperate to restore caspase-8 expression and sensitize resistant
      neuroblastoma and medulloblastoma cells to TRAIL-induced apoptosis, our findings
      have important implications for novel strategies targeting defective apoptosis
      pathways in neuroectodermal tumors.

PMID- 16607284
TI  - The identification of an internal ribosomal entry site in the 5'-untranslated
      region of p53 mRNA provides a novel mechanism for the regulation of its
      translation following DNA damage.
AB  - The tumor suppressor p53 plays a crucial role in maintaining the genetic
      integrity of the cell and in suppressing cell transformation. Its cellular levels
      are usually low and rise substantially in response to DNA damage. Although
      research on p53 induction following DNA damage has mainly focused on the post
      translational modification of p53 by Mdm2, it is known that protein translation
      also contributes to p53 induction. However, the mechanisms underlying
      translational regulation of the p53 protein in response to DNA damage are still
      poorly understood. We show that p53 synthesis increases dramatically in MCF-7
      cells treated with etoposide. Interestingly, this increase is accompanied by an
      increase in the association of the translation initiation factor eIF-4E with its
      binding protein 4E-BP1, an inhibitor of cap-dependent protein translation. We
      further identified an internal ribosomal entry site (IRES) located in the 5'
      untranslated region of the p53 transcript, that is capable of driving the cap
      independent translation of a downstream cistron encoding Firefly luciferase in a
      dicistronic expression vector. Moreover, we found that the activity of the IRES
      element increases in response to etoposide-induced DNA damage in MCF-7 cells.
      These findings provide a novel mechanism for the regulation of p53 translation in
      response to DNA damage.

PMID- 16607285
TI  - Hepatocellular carcinoma in Txnip-deficient mice.
AB  - The molecular pathogenesis and the genetic aberrations that lead to the
      progression of hepatocellular carcinoma (HCC) are largely unknown. Here, we
      demonstrate that the thioredoxin interacting protein (Txnip) gene is a candidate
      tumor suppressor gene in vivo. We previously showed that the recombinant inbred
      congenic strain HcB-19 has a spontaneous mutation of the Txnip gene, and we now
      show that the strain has dramatically increased incidence of HCC, and that the
      HCC cosegregates with the Txnip mutation. Approximately 40% of the Txnip
      deficient mice developed hepatic tumors with an increased prevalence in male
      mice. Visible tumors develop as early as 8 months of age. Histological analysis
      confirmed the morphology of HCC in the Txnip-deficient mice. Molecular markers of
      HCC, alpha-fetoprotein and p53, were increased in tumors of Txnip-deficient mice.
      The upregulation of p53 preceded tumor development; however, bromodeoxyuridine
      (BrdU) labeling of normal hepatic tissue of Txnip-deficient mice did not reveal
      increased cell proliferation. Finally, microarray analyses of tumor, non-tumor
      adjacent, and normal tissue of Txnip-deficient mice highlighted the genetic
      differences leading to the predisposition and onset of HCC. Our findings suggest
      that Txnip deficiency is sufficient to initiate HCC and suggest novel mechanisms
      in hepatocarcinogenesis.

PMID- 16607286
TI  - A crucial function of PDGF in TGF-beta-mediated cancer progression of
      hepatocytes.
AB  - Polarized hepatocytes expressing hyperactive Ha-Ras adopt an invasive and
      metastatic phenotype in cooperation with transforming growth factor (TGF)-beta.
      This dramatic increase in malignancy is displayed by an epithelial to mesenchymal
      transition (EMT), which mimics the TGF-beta-mediated progression of human
      hepatocellular carcinomas. In culture, hepatocellular EMT occurs highly
      synchronously, facilitating the analysis of molecular events underlying the
      various stages of this process. Here, we show that in response to TGF-beta,
      phosphorylated Smads rapidly translocated into the nucleus and activated
      transcription of target genes such as E-cadherin repressors of the Snail
      superfamily, causing loss of cell adhesion. Within the TGF-beta superfamily of
      cytokines, TGF-beta1, -beta2 and -beta3 were specific for the induction of
      hepatocellular EMT. Expression profiling of EMT kinetics revealed 78 up- and 235
      downregulated genes, which preferentially modulate metabolic activities,
      extracellular matrix composition, transcriptional activities and cell survival.
      Independent of the genetic background, platelet-derived growth factor (PDGF)-A
      ligand and both PDGF receptor subunits were highly elevated, together with
      autocrine secretion of bioactive PDGF. Interference with PDGF signalling by
      employing hepatocytes expressing the dominant-negative PDGF-alpha receptor
      revealed decreased TGF-beta-induced migration in vitro and efficient suppression
      of tumour growth in vivo. In conclusion, these results provide evidence for a
      crucial role of PDGF in TGF-beta-mediated tumour progression of hepatocytes and
      suggest PDGF as a target for therapeutic intervention in liver cancer.

PMID- 16607287
TI  - Organelles on the move: insights from yeast vacuole inheritance.
AB  - Organelle inheritance is one of several processes that occur during cell
      division. Recent studies on yeast vacuole inheritance have indicated rules that
      probably apply to most organelle-inheritance pathways. They have uncovered a
      molecular mechanism for membrane-cargo transport that is partially conserved from
      yeast to humans. They have also shown that the transport complex, which is
      composed of a molecular motor and its receptor, regulates the destination and
      timing of vacuole movement and might coordinate organelle movement with several
      other organelle functions.

PMID- 16607288
TI  - NDR kinases regulate essential cell processes from yeast to humans.
AB  - Members of the NDR (nuclear Dbf2-related) protein-kinase family are essential
      components of pathways that control important cellular processes, such as
      morphological changes, mitotic exit, cytokinesis, cell proliferation and
      apoptosis. Recent progress has shed light on the mechanisms that underlie the
      regulation and function of the NDR family members. Combined data from yeast,
      worms, flies, mice and human cells now highlight the conserved and important
      roles of the different NDR kinases in distinct cellular processes.

PMID- 16607289
TI  - Local force and geometry sensing regulate cell functions.
AB  - The shapes of eukaryotic cells and ultimately the organisms that they form are
      defined by cycles of mechanosensing, mechanotransduction and mechanoresponse.
      Local sensing of force or geometry is transduced into biochemical signals that
      result in cell responses even for complex mechanical parameters such as substrate
      rigidity and cell-level form. These responses regulate cell growth,
      differentiation, shape changes and cell death. Recent tissue scaffolds that have
      been engineered at the micro- and nanoscale level now enable better dissection of
      the mechanosensing, transduction and response mechanisms.

PMID- 16607290
TI  - Sperm guidance in mammals - an unpaved road to the egg.
AB  - Contrary to the prevalent view, there seems to be no competition in the mammalian
      female genital tract among large numbers of sperm cells that are racing towards
      the egg. Instead, small numbers of the ejaculated sperm cells enter the Fallopian
      tube, and these few must be guided to make the remaining long, obstructed way to
      the egg. Here, we review the mechanisms by which mammalian sperm cells are guided
      to the egg.

PMID- 16607291
TI  - Women in cell biology: getting to the top.
AB  - Those who write about women scientists tend to treat us as a group, documenting
      our demise at each career stage and discussing measures to prevent this. By
      contrast, my approach has been to focus on individual women who have 'made it' in
      science and to ask how their careers have been affected by their sex. Some
      positive conclusions emerge, but the overall picture is disheartening.

PMID- 16607292
TI  - Job done.

PMID- 16607293
TI  - Propolis: a background.

PMID- 16607294
TI  - Academic plight.

PMID- 16607295
TI  - Opportunistic and reprehensible.

PMID- 16607297
TI  - Courage for debate.

PMID- 16607299
TI  - OMFS training revisited.

PMID- 16607301
TI  - Climbing every mountain.

PMID- 16607302
TI  - Worthwhile projects.

PMID- 16607303
TI  - Caries before concrescence?

PMID- 16607304
TI  - Immediate referral.

PMID- 16607308
TI  - Follow the guidelines.

PMID- 16607309
TI  - Multi vs. single dose.

PMID- 16607312
TI  - FGDP (UK) and FDS move to establish joint college.

PMID- 16607324
TI  - Hydrogen peroxide tooth-whitening (bleaching) products: review of adverse effects
      and safety issues.
AB  - Hydrogen peroxide in the form of carbamide peroxide is widely used for tooth
      whitening (bleaching), both in professionally- and in self-administered products.
      Adverse effects have become evident. Cervical root resorption is a possible
      consequence of internal bleaching and is more frequently observed in teeth
      treated with the thermo-catalytic procedure. Tooth sensitivity is experienced in
      15-78% of patients undergoing external tooth bleaching. However, clinical studies
      addressing other adverse effects are lacking. Direct contact with hydrogen
      peroxide induces genotoxic effects in bacteria and cultured epithelial cells, but
      the effect is reduced or totally abolished in the presence of metabolising
      enzymes. Several carcinogenesis studies, including the hamster cheek pouch model,
      indicate that hydrogen peroxide (H(2)O(2)) might possibly act as a promoter.
      Until further clinical research is concluded to address the question of possible
      carcinogenicity, it is recommended that: tooth-bleaching products using
      concentrated H(2)O(2) should not be used without gingival protection; that
      H(2)O(2) containing products should be avoided in patients with damaged or
      diseased soft tissues. For nightguard vital bleaching, minimal amounts of low
      dose H(2)O(2) (including in the form of carbamide peroxide) are preferred,
      thereby avoiding prolonged and concentrated exposures.

PMID- 16607325
TI  - Non-carious tooth conditions in children in the UK, 2003.
AB  - BACKGROUND: The 2003 Children's Dental Health Survey is the fourth of the 10
      yearly surveys of children's oral health. AIM: To report the prevalence of three
      non-carious tooth conditions in children in the UK. METHOD: A representative
      sample of children five, eight, 12 and 15 years of age were examined by
      calibrated examiners in schools across the UK. The dental examination included
      accidental damage to incisors, tooth surface loss (TSL) and enamel opacities (age
      12 only). A postal questionnaire sought parental and child views on marks on
      teeth which could not be removed by brushing. RESULTS: The proportion of children
      sustaining accidental damage to permanent incisors decreased to 11% of 12 and 13%
      of 15-year-olds, but the majority of accidental damage remained untreated. TSL
      was found on 53% of five-year-olds and on approximately a third of 12 and 15-year
      olds. There was a statistically significant change for TSL on permanent teeth at
      age 15 where 27% upper incisors had TSL palatally in 1993 compared to 33% in
      2003. Thirty-four per cent of 12-year-old children had enamel opacities on one or
      more of their teeth compared with 36% in 1993. CONCLUSIONS: Tooth surface loss
      remains a common finding in children in the UK. A large proportion of accidental
      damage to teeth remains untreated.

PMID- 16607332
TI  - Provision of prevention to adults in NHS dental practices and attitudes to
      prevention.
AB  - AIMS: To identify the number of claims reported by the Dental Practice Board
      (DPB) for the three adult preventive codes for the year ending October 2002 in
      Wales. To identify the attitudes of practitioners to the use of these codes.
      DESIGN: A cross-sectional study using routinely gathered DPB data and data
      generated by a postal questionnaire. SAMPLE: All DPB claims for the 12 months
      ending October 2002. A randomised sample of 400 dentists currently practising in
      Wales for the postal questionnaire. RESULTS: The DPB data showed great variation
      across Wales for: the number, type and distribution of preventive code claims;
      the age and payment status of patients prescribed these treatments; and the
      proportion of male versus female dentists claiming for the codes. The
      questionnaire response rate was 67% (n = 267). The results showed that most
      respondents were deterred by the restrictions on the codes, insufficient
      reimbursement and a perceived unwillingness of patients to pay for preventive
      care. CONCLUSION: Few dentists provide preventive care to adults under the
      existing remuneration system. Work is necessary to enable dentists to use
      effective preventive techniques for adult patients. These results can be
      considered to show the baseline provision of prevention and could facilitate the
      evaluation of any changes to the current system.

PMID- 16607333
TI  - Revalidation of general dental practitioners in Scotland: the results of a pilot
      study. Part 1--feasibility of operation.
AB  - AIM: To devise and operate a pilot scheme of revalidation for general dental
      practitioners. METHOD: A representative group of dental practitioners was
      convened to advise on an approach to piloting revalidation. Ten general dental
      practitioners volunteered and completed portfolios of evidence of fitness to
      practise. The portfolios were assessed by a panel of three calibrated experts,
      using a specially developed assessment tool. A single decision "evidence
      presented allowed revalidation to be recommended" was made. A timesheet was used
      to record the time spent producing the portfolio. RESULTS: Eight portfolios were
      assessed as sufficient for revalidation purposes. Two dentists were required to
      make supplementary submissions of evidence before they were found to be
      acceptable. An average of eight hours of dentist time and six hours of delegated
      time was spent producing the portfolios. CONCLUSIONS: The small number of
      dentists in this pilot were able to use the portfolio satisfactorily. The
      dentists were all volunteers and so may not necessarily be fully representative
      of the profession. The time spent completing the portfolio was not considered
      excessive. The assessors were adequately prepared and calibrated for their work.

PMID- 16607351
TI  - The urologist and medical imaging.

PMID- 16607352
TI  - The use of androgens for female sexual dysfunction.

PMID- 16607368
TI  - The indications for partial nephrectomy in the treatment of renal cell carcinoma.
AB  - Partial nephrectomy is performed more frequently for small, incidentally
      discovered, low-stage renal tumors. Importantly, one should distinguish the
      imperative indications for such surgery from the relative and elective
      indications, while taking contraindications to nephron-sparing surgery into
      account. The main advantage of partial nephrectomy over radical nephrectomy is
      the avoidance of renal insufficiency; the major disadvantages include the
      possibility of local recurrence and perioperative complications. In this article,
      the literature on nephron-sparing surgery was reviewed in order to put the
      management of renal cancer into a modern perspective.

PMID- 16607369
TI  - Mechanisms of disease: role of purinergic signaling in the pathophysiology of
      bladder dysfunction.
AB  - Although the 'purinergic nerve hypothesis' proposed by Burnstock in the early
      1970s was met with considerable skepticism, it is now accepted that certain
      neurons use a purine nucleotide or nucleoside such as ATP or adenosine as a
      neurotransmitter. Likewise, early studies indicated that the human bladder is
      devoid of purinergic nerves mediating contraction; however, later studies
      demonstrated that purinergic nerve-mediated bladder contraction is increased in
      pathologic conditions such as interstitial cystitis. Cloning and sequencing
      studies have revealed four subtypes of adenosine receptors and eight subtypes of
      P2Y receptors, all of which are G-protein-coupled receptors. There are no reports
      of the cellular location of these receptors in the human bladder. P2X receptors
      are ligand-gated ion channels, and seven subunits have been cloned and sequenced.
      Immunohistochemical studies have determined that P2X(1,2,4) subunits are on
      detrusor-muscle cells, P2X(1-3,5) subunits are on bladder nerves and P2X(2,3,5)
      subunits are on bladder urothelial cells. Development of purinergic antagonist
      drugs with selectivity for P2X(1) receptors on detrusor muscle cells might be
      useful for treatment of detrusor overactivity. Antagonists with selectivity for
      P2X(3) receptors on bladder sensory nerves might be clinically beneficial for
      treatment of urinary urgency, and perhaps chronic pelvic pain.

PMID- 16607370
TI  - Technology insight: monoclonal antibody imaging of prostate cancer.
AB  - Imaging is a critical component of diagnosis, staging and monitoring, all of
      which factor heavily in treatment decision-making for cancer patients. Agents,
      such as antibodies, can target molecules that are relatively unique to cancer
      cells. Prostate-specific membrane antigen (PSMA) is the most well-established,
      highly restricted prostate-cancer-related cell membrane antigen known. Ten years
      ago, the FDA approved (111)In-capromab pendetide for use in imaging soft-tissue,
      but not bone, sites of metastatic prostate cancer for presurgical staging or the
      evaluation of PSA relapse after local therapy. For presurgical patients with high
      risk disease but negative bone, CT and MRI scans, capromab demonstrated the
      ability to identify some patients with positive nodes, thereby sparing them an
      unnecessary surgical procedure. But there have been no follow-up studies to
      indicate that high-risk patients with a negative capromab scan have a lower
      failure rate after surgery. In the setting of PSA relapse, capromab is
      compromised by its inability to sensitively image bone metastases; bone is the
      first site of metastatic prostate cancer in 72% of patients. The problem with
      imaging bone metastases is that capromab detects an antigenic site on the
      intracellular portion of PSMA-a site not accessible to circulating antibodies.
      Early results indicate that second-generation antibodies that target the
      extracellular domain of PSMA might provide significant benefits in the imaging of
      prostate cancer.

PMID- 16607371
TI  - Chylous ascites following retroperitoneal lymphadenectomy for testes cancer.
AB  - BACKGROUND: A 31-year-old man underwent a radical orchiectomy for a stage I mixed
      germ-cell tumor with angiolymphatic invasion. A subsequent laparoscopic
      retroperitoneal lymphadenectomy was complicated by a laceration to the aorta at
      the ostia of the more inferior of two right renal arteries. This was repaired
      following conversion to an open laparotomy. The patient presented 14 days later
      with genital swelling and increasing abdominal girth. INVESTIGATIONS: Physical
      examination, abdominal and pelvic CT, laboratory albumin testing,
      lymphoscintogram and lymphangiogram. DIAGNOSIS: Chylous ascites with tracking of
      lymphatic fluid into the left groin through a defect in the internal inguinal
      ring. MANAGEMENT: Conservative management with salt restriction, a medium-chain
      fatty-acid diet and diuretics; exploratory laparoscopy, during which a small left
      inguinal hernia was repaired and chylous fluid was drained. Following further
      leakage, the patient was placed on total parenteral nutrition, followed by image
      guided sclerotherapy with doxycycline.

PMID- 16607372
TI  - Comprehensive analysis of HE4 expression in normal and malignant human tissues.
AB  - The HE4 (WFDC2) gene encodes a WAP-type four disulphide core domain-containing
      protein with a presumptive role in natural immunity. Multiple studies have
      consistently identified upregulation of HE4 gene expression in carcinomas of the
      ovary; however, the expression in normal and malignant adult tissues has not been
      examined in detail. Here, we examined the expression of the HE4 gene and protein
      in a large series of normal and malignant adult tissues by oligonucleotide
      microarray and tissue microarray, respectively. HE4 gene expression was highest
      in normal human trachea and salivary gland, and to a lesser extent, lung,
      prostate, pituitary gland, thyroid, and kidney. In a series of 175 human adult
      tumors, gene expression was highest in ovarian serous carcinomas. However,
      adenocarcinomas of the lung, and occasional breast, transitional cell and
      pancreatic carcinomas had moderate or high levels of HE4 expression. Using tissue
      microarrays and full tissue sections of normal and 448 neoplastic tissues, HE4
      immunoreactivity was found in normal glandular epithelium of the female genital
      tract and breast, the epididymis and vas deferens, respiratory epithelium, distal
      renal tubules, colonic mucosa, and salivary glands, consistent with HE4 gene
      expression. In addition to consistent positivity in ovarian carcinoma, some
      pulmonary, endometrial, and breast adenocarcinomas, mesotheliomas, and less
      often, gastrointestinal, renal and transitional cell carcinomas were also
      positive. Knowledge of the expression patterns of HE4 in our survey is useful for
      application in histopathologic diagnosis, and should be taken into consideration
      in future studies that examine the role of HE4 as a serological tumor biomarker
      or as a target for gene-based therapy.

PMID- 16607373
TI  - Molecular genetic analysis of central nervous system germ cell tumors with
      comparative genomic hybridization.
AB  - The limited information available to date regarding the genetic alterations in
      germ cell tumors of the central nervous system has raised concerns about their
      biologic relationship to other germ cell tumor entities. We investigated fresh
      frozen or archival tumor samples from 19 patients with central nervous system
      germ cell tumors (CNS-GCTs), including seven germinomas, eight malignant
      nongerminomatous germ cell tumors and four teratomas, using chromosomal
      comparative genomic hybridization to determine recurrent chromosomal imbalances.
      All 15 malignant CNS-GCTs and two of four teratomas showed multiple chromosomal
      imbalances. Chromosomal gains (median: 4 gains/tumor, range: 0-9 gains/tumor)
      were observed more frequently than losses (median: 1.6 losses/tumor, range: 0-6
      losses/tumor). Gain of 12p, which is considered characteristic for germ cell
      tumors of the adult testis, was detected in 11 of 19 tumors and 10 of 15
      malignant CNS-GCTs. In one tumor, gain of 12p was confined to an amplicon at
      12p12, corresponding to the commonly amplified region on 12p. Other common gains
      were found on chromosome arms 1q and 8q (n = 9, each). Among the chromosomal
      losses, parts of chromosome 11 (n = 5), 18 (n = 4), and 13 (n = 3) were deleted
      most frequently. Notably, we observed no difference in the genetic profiles of
      germinomatous and nongerminomatous CNS-GCTs; however, the average number of
      imbalances was higher in the latter group. A meta-analysis comparing 116
      malignant gonadal and extragonadal germ cell tumors revealed that the genomic
      alterations in CNS-GCTs are virtually indistinguishable from those found in their
      gonadal or other extragonadal counterparts of the corresponding age group. These
      data strongly argue in favor of common pathogenetic mechanisms in gonadal and
      extragonadal germ cell tumors.

PMID- 16607374
TI  - Low sensitivity of histology to predict the presence of microorganisms in
      suspected aseptic loosening of a joint prosthesis.
AB  - Intraoperative histology has a high specificity and sensitivity when a septic
      prosthesis loosening is suspected. However, its usefulness to predict the
      presence of microorganisms when aseptic loosening is suspected is not well
      defined. Intraoperative histology and cultures from periprosthetic tissue of 61
      revision arthroplasties performed owing to suspected aseptic loosening were
      retrospectively reviewed. Frozen sections were evaluated following Mirra's
      criteria (adapted by Feldman). Culture was considered positive when the same
      microorganism was isolated in at least two samples. The cultures were positive in
      12 cases and coagulase-negative staphylococci were the most common microorganisms
      (11 cases). In six out of 12 cases (50%), the histology revealed more than five
      polymorphonuclear leukocytes per high-power field. The sensitivity, specificity,
      positive and negative predictive value of histology to detect the presence of
      microorganisms was 50, 81, 40 and 86%, respectively. In conclusion,
      intraoperative histology using Mirra's criteria had a low sensitivity to predict
      the presence of microorganisms in samples from suspected aseptic prosthetic
      loosening.

PMID- 16607375
TI  - Spatial and temporal heparanase expression in colon mucosa throughout the adenoma
      carcinoma sequence.
AB  - Heparanase is a mammalian endo-beta-D-glucuronidase that cleaves heparan sulfate
      side chains at a limited number of sites. Such enzymatic activity is thought to
      participate in degradation and remodeling of the extracellular matrix and to
      facilitate cell invasion associated with tumor metastasis, angiogenesis and
      inflammation. Traditionally, heparanase activity was well correlated with the
      metastatic potential of a large number of tumor-derived cell types. More
      recently, heparanase upregulation has been documented in an increasing number of
      primary human tumors, correlating with poor postoperative survival and increased
      tumor vascularity. Here, we employed anti-heparanase 733 polyclonal antibody that
      preferentially recognizes the 50 kDa active heparanase subunit over the 65 kDa
      proenzyme, as well as anti-heparanase 92.4 monoclonal antibody that recognizes
      both the latent and the active enzyme, to follow heparanase expression,
      processing and localization throughout the adenoma-carcinoma transition of the
      colon epithelium. Normal (nondysplastic) mucosa of the large bowel near
      epithelial neoplasms, as well as areas of mild dysplasia in adenomas, exhibited a
      strong reactivity with antibody 733 that became even stronger in foci of moderate
      dysplasia. Interestingly, although reactivity with antibody 733 was markedly
      reduced in severe dysplasia and in colorectal carcinoma, response to antibody
      92.4 exhibited the opposite trend and staining intensities increased in parallel
      with tumor stage, the highest being in carcinoma cells. Involvement of latent
      heparanase (detected by 92.4, but not by 733 antibody) in tumor progression was
      suggested by activation of the Akt/PKB signal transduction pathway upon
      heparanase overexpression or exogenous addition to HT29 human colon carcinoma
      cells. These results suggest that heparanase expression is induced during colon
      carcinogenesis, and that its processing, conformation and localization are
      tightly regulated during the course of colon adenoma-carcinoma progression.

PMID- 16607376
TI  - Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade
      prostatic intraepithelial neoplasia.
AB  - Typically glands of prostatic adenocarcinoma have a single cell lining, although
      stratification can be seen in invasive carcinomas with a cribriform architecture,
      including ductal carcinoma. The presence and diagnostic significance of
      stratified cells within non-cribriform carcinomatous prostatic glands has not
      been well addressed. The histomorphological features and immunohistochemical
      profile of cases of non-cribriform prostatic adenocarcinoma with stratified
      malignant glandular epithelium were analyzed. These cases were identified from
      needle biopsy cases from the consultation files of one of the authors and from a
      review of 150 consecutive in-house needle biopsy cases of prostatic
      adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive
      against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl
      coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from
      the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands
      having stratified epithelium was the sole carcinomatous component in the biopsy,
      while such a component represented 5-30% of the invasive carcinoma seen elsewhere
      in the remaining cases. The main attribute in all these foci was the presence of
      glandular profiles lined by several layers of epithelial cells with cytological
      and architectural features resembling flat or tufted high-grade prostatic
      intraepithelial neoplasia, but lacking basal cells as confirmed by negative
      34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the
      stratified foci was variable, with 4 foci showing positivity, and 3 foci being
      negative, including two cases that displayed AMACR positivity in adjacent non
      stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified
      malignant glandular epithelium can be identified in prostate needle biopsy
      samples harboring non-cribriform prostatic adenocarcinoma and resembles glands
      with high-grade prostatic intraepithelial neoplasia. These 'PIN-like' carcinomas
      can present in pure form. Recognition of this pattern of prostatic adenocarcinoma
      is necessary to correctly diagnose such cases as invasive carcinoma.

PMID- 16607377
TI  - hMLH1 and MGMT inactivation as a mechanism of tumorigenesis in monoclonal
      gammopathies.
AB  - Monoclonal gammopathies are a group of disorders characterized by clonal
      proliferation and accumulation of immunoglobulin-producing plasma cells. Multiple
      myeloma and monoclonal gammopathy of undetermined significance are the most
      common monoclonal gammopathies; the two comprise a spectrum of disorders, ranging
      from a relatively benign disease, monoclonal gammopathy of undetermined
      significance, to a malignant disease, multiple myeloma. Aberrant promoter
      methylation represents a primary mechanism of gene silencing during
      tumorigenesis. DNA repair systems act to maintain genome integrity in the
      presence of replication errors, environmental insults, and the cumulative effects
      of aging. The methylation patterns of two genes implicated in DNA repair, O6
      methylguanine DNA methyl-transferase (MGMT) and human mutL homologue1 (hMLH1)
      have been detected in various solid tumours. With the purpose of studying the
      gene silencing of MGMT and hMLH1 in plasma cell disorders, we investigated the
      methylation status and expression of both genes in: 29 cases of multiple myeloma;
      one case of plasma cell leukaemia; 13 cases of monoclonal gammopathy of
      undetermined significance; and two cases of polyclonal plasmacytosis, using
      methylation-specific polymerase-chain reaction and immunohistochemical
      techniques. Methylation frequencies for MGMT were 23% in multiple myeloma and 8%
      in monoclonal gammopathy of undetermined significance. It was 10% for hMLH1 in
      multiple myeloma. None of the patients diagnosed with monoclonal gammopathy of
      undetermined significance had hMLH1 hypermethylated. In addition, 50% of myeloma
      cases had a loss of hMLH1 expression, whereas silencing of MGMT was observed in
      43% of myeloma and 36% of samples with monoclonal gammopathy of undetermined
      significance. This study indicates that repair pathway defects play a role in the
      pathogenesis and evolution of monoclonal gammopathies, and suggests that
      inactivation of hMLH1 could be implicated in multiple myeloma tumorigenesis.

PMID- 16607378
TI  - Targeted imaging of human endothelial-specific marker in a model of adoptive cell
      transfer.
AB  - Imaging of endothelial-specific markers is critically important in non-invasive
      detection of early signs of vascular pathologies (eg inflammation,
      atherosclerosis and angiogenesis). A model of adoptive human endothelial cell
      (HUVEC) transfer was used to test-specific imaging probes for human vascular
      disease consisting of cross-linked iron oxide (CLIO) nanoparticles conjugated to
      anti-human E-selectin (CLIO-F(ab')(2)). To perform in vivo imaging of E-selectin
      expression in functional blood vessels, human vascular endothelium cells (HUVECs)
      were implanted in athymic mice in Matrigel solution, which served as a temporary
      neovascularization scaffold after the solidification. The formation of HUVEC
      containing vessels was established by histology and microscopy. CLIO-F(ab')(2)
      probes were administered via an i.v. injection following the induction of E
      selectin expression by IL-1beta. High-resolution MR images were obtained before
      and after the administration of CLIO-F(ab')(2), which showed specific
      hypointensity only if treated with IL-1beta. A three-times higher CLIO-induced MR
      signal decrease on T2(*) images was measured in HUVEC implants in response to IL
      1beta treatment. Image signal intensity did not change in control animals that:
      (1) harbored Matrigel alone, (2) in the absence of IL-1beta treatment or (3) in
      animals injected with CLIO linked to the idiotype-matched control F(ab')(2).
      Experiments in an adoptive transfer model demonstrated that HUVEC-containing
      neovessels are perfused and that IL-1beta inducible E-selectin expression in
      these vessels is detectable with non-invasive imaging by using targeted
      nanoparticles.

PMID- 16607379
TI  - Endothelial cell expression of galectin-1 induced by prostate cancer cells
      inhibits T-cell transendothelial migration.
AB  - A critical control point in the immune response to tumors or to pathogens is the
      egress of lymphocytes from blood into damaged or infected tissue. While several
      specific endothelial cell proteins promote lymphocyte adhesion to and migration
      across endothelium, little is known about endothelial cell surface proteins that
      negatively regulate transendothelial migration of lymphocytes. Galectin-1 is a
      mammalian lectin expressed by a variety of cell types, including endothelial
      cells, that has pleiotropic anti-inflammatory effects. Galectin-1 is known to
      alter T-cell cytokine production and to trigger T-cell death. We now demonstrate
      that galectin-1 inhibits T-cell migration across endothelial cells, identifying a
      novel anti-inflammatory effect of galectin-1. We observed reduced T-cell
      migration across endothelial cells induced to increase galectin-1 expression by
      exposure to prostate cancer cell conditioned medium, compared to T-cell migration
      across control-treated endothelial cells, and the inhibitory effect of galectin-1
      on T-cell migration was reversed by specific antiserum. Decreased T-cell
      migration was not due to decreased adhesion to galectin-1 expressing endothelial
      cells, nor to death of T cells, as T cells lacking core 2 O-glycans and thus
      resistant to galectin-1 death displayed reduced migration across endothelial
      cells. Galectin-1 on the surface of extracellular matrix also reduced the ability
      of T cells to migrate through the matrix. T cells bound to galectin-1-coated
      matrix demonstrated enhanced clustering of CD43, including at the T-cell:matrix
      interface, compared to CD43 on T cells bound to matrix in the absence of galectin
      1. As translocation of CD43 to the trailing edge is essential for polarized T
      cell migration, these data indicate that galectin-1-mediated clustering of CD43
      contributes to the inhibitory effect on T-cell migration. Inhibition of T-cell
      migration is a novel anti-inflammatory activity of galectin-1.

PMID- 16607380
TI  - Inhibition of SCF attenuates peribronchial remodeling in chronic cockroach
      allergen-induced asthma.
AB  - The progression and severity of chronic asthma likely depends upon the intensity
      of the damage and remodeling of the tissue. We have developed a chronic model of
      allergic asthma using multiple cockroach allergen challenges. Using this
      clinically relevant allergen we have established significant peribronchial
      fibrosis and mucus overproduction. These remodeling events are accompanied by
      intense peribronchial inflammation, including lymphocytes and eosinophils. A
      cytokine that has been identified as having a prominent role in short-term
      allergic events, stem cell factor (SCF), appears to have a significant role in
      this late-stage process. Using our polyclonal antibody specific for SCF
      administered into the airways of mice during the final allergen challenges, we
      find a significant effect on the chronic peribronchial allergen-induced fibrotic
      remodeling. This was characterized by reduced inflammation, especially
      eosinophils, as well as reduced hydroxyproline levels in anti-SCF compared to
      control antibody-treated animals. In addition, when we examined chemokines
      associated with the chronic disease and neutralized SCF in vivo we observed a
      corresponding decrease in CCL6 and CCL17. Using an inhibitor, imatinib mesylate,
      that blocks SCF/c-kit-associated RTK, we find similar results as with anti-SCF
      for attenuating AHR and fibrotic changes, suggesting that a potential clinical
      treatment for chronic asthma already exists related to this pathway. These
      results further support the potential use of SCF/c-kit inhibition for targeting
      chronic severe asthmatic responses.

PMID- 16607381
TI  - Use of a novel FISH assay on paraffin-embedded tissues as an adjunct to diagnosis
      of alveolar rhabdomyosarcoma.
AB  - A valuable diagnostic adjunct and important prognostic parameter in alveolar
      rhabdomyosarcoma (ARMS) is the identification of translocations t(2;13)(q35;q14)
      and t(1;13)(p36;q14), and the associated PAX3-FKHR and PAX7-FKHR fusion
      transcripts, respectively. Most RMS fusion gene type studies have been based on
      reverse transcriptase-polymerase chain reaction (RT-PCR) detection of the fusion
      transcript, a technique limited by RNA quality and failure of devised primer sets
      to detect unusual variants. As an alternative approach, we developed a
      fluorescence in situ hybridization (FISH) assay that can: (1) distinguish between
      the two most common ARMS-associated fusion genes; (2) identify potential unusual
      variant translocations; (3) assess histologic components in mixed
      alveolar/embryonal RMS; and (4) be performed on paraffinized tissue. FISH
      analyses of 75 specimens (40 ARMS, 16 ERMS, 8 mixed ARMS/ERMS, and 11 non-RMS
      tumors) using selected cosmid clone, bacterial, P1-derived, and yeast artificial
      chromosome probe sets were successful in all but two cases. Among specimens with
      informative results for both FISH and RT-PCR or standard karyotyping, PAX/FKHR
      classification results were concordant in 94.6% (53/56). The three discordant
      cases included one exhibiting a t(2;13) by FISH that was subsequently confirmed
      by repeat RT-PCR, a second showing a rearrangement of the PAX3 locus only
      (consistent with the presence of a PAX3 variant translocation), and a third
      revealing a t(2;13) by FISH that lacked this translocation cytogenetically. Both
      alveolar and embryonal components of the mixed ARMS/ERMS subtype were negative
      for PAX3, PAX7, and FKHR rearrangements, a surprising finding confirmed by RT-PCR
      and/or conventional karyotyping. These data demonstrate that FISH with newly
      designed probe sets is a reliable and highly specific method of detecting t(1;13)
      and t(2;13) in routinely processed tissue and may be useful in differentiating
      ARMS from other small round cell tumors. The findings also suggest that FISH may
      be a more sensitive assay than RT-PCR in some settings, capable of revealing
      variant translocations.

PMID- 16607382
TI  - Sex differences in the relationships between BMI, WHR and incidence of
      cardiovascular disease: a population-based cohort study.
AB  - OBJECTIVE: Body mass index (BMI) is associated with increased incidence of
      cardiovascular disease (CVD). However, the risk could be very different for
      individuals with the same body mass. The present study explored whether regional
      fat distribution, as measured by waist-hip ratio (WHR), could modify the impact
      of BMI on the risk of CVD in men and women. DESIGN: Prospective population-based
      study. SUBJECTS: A total of 10 369 men and 16 638 women, 45-73 years old, from
      general population in Malmo, Sweden. MEASUREMENTS: All subjects were followed
      over 7 years for the incidences of first-ever cardiac event (CE) and ischemic
      stroke in relation to BMI category (<25.0, 25.0-29.9, > or =30.0) and WHR.
      RESULTS: The prevalence of overweight and obesity was 39.4 and 13.0%,
      respectively. During follow-up, 1280 subjects suffered a CVD event (750 CE, 530
      ischemic stroke). The risk of CVD in women increased with increasing levels of
      WHR, irrespective of BMI category. In men, WHR (per 1 s.d. increase) was
      associated with increased incidence of CVD in those with normal weight (relative
      risk (RR)=1.24; 95% CI: 1.13-1.37) after adjustments for confounding factors.
      However, WHR was not related to CVD in overweight men (RR=1.06; 95%CI: 0.94-1.20)
      or obese men (RR=1.04; 95%CI: 0.87-1.24). A significant interaction was observed
      between sex and WHR on the CVD risk. CONCLUSION: The effect of WHR on incidence
      of CVD is modified by the overall body weight and by gender. WHR adds prognostic
      information on the cardiovascular risk in women at all levels of BMI, and in men
      with normal weight.

PMID- 16607383
TI  - The association of SNP276G>T at adiponectin gene with circulating adiponectin and
      insulin resistance in response to mild weight loss.
AB  - OBJECTIVE: The purpose of this study was to determine whether common single
      nucleotide polymorphisms (SNPs) at the adiponectin (ADIPOQ) locus influence
      changes in circulating adiponectin and the features of insulin resistance in
      response to a weight loss intervention. SUBJECTS: In total, 294
      nondiabetic/overweight-obese Koreans participated in a clinical intervention
      study lasting 12 weeks involving a caloric reduction of -300kcal/day. METHODS:
      Plasma adiponectin, blood lipids, glucose and insulin concentrations were
      measured at baseline and after weight loss. Insulin resistance was estimated by
      homeostasis model assessment insulin resistance (HOMA-IR) derived from fasting
      glucose and insulin concentrations. We genotyped for three SNPs, 45T>G, 276G>T
      and -11377C>G. RESULTS: At baseline, HOMA-IR was significantly higher in GG
      homozygotes than in carriers of the T allele at SNP276G>T of the adiponectin gene
      (P<0.05). With regard to SNP45T>G and SNP -11377C>G, we did not find any genotype
      related differences in baseline levels of HOMA-IR and adiponectin. In the 45/276
      haplotype test, homozygous for the TG haplotype had significantly lower
      concentrations of plasma adiponectin (P<0.05). After the 12-week weight loss
      intervention, the significant decreases in HOMA-IR (P<0.001) and increases in
      adiponectin (P<0.01) were observed in GG homozygotes at SNP276, which were not
      shown in carriers of the T allele. Furthermore, there was a significant
      difference in the decreases in HOMA-IR between the GG homozygotes and carriers of
      the T allele at SNP276 (P<0.05). Regarding SNP45T>G and SNP -11377C>G, there was
      no association between SNP45T>G and SNP -11377C>G and decreases in HOMA-IR. In
      the 45/276 haplotype test, there was a significant difference in changes of
      adiponectin levels among those with different haplotype combinations (P<0.05).
      CONCLUSION: The SNP276G>T of the ADIPOQ gene is associated with different
      responses of circulating adiponectin and insulin resistance to mild weight loss
      in overweight-obese subjects.

PMID- 16607384
TI  - The association of parental characteristics and psychological problems in obese
      youngsters.
AB  - OBJECTIVE: The aim of the present study was to examine to what extent parental
      psychological characteristics and parental behavior are related to psychological
      problems in obese youngsters. RESEARCH METHODS: Data were collected from 196
      families having an overweight youngster (range 10-16 years old) (mean body mass
      index (BMI)=31.2; s.d.=5.3) seeking weight-loss treatment and compared with data
      from normal weight samples. Behavior problems were measured using the Child
      Behavior Checklist; the Child version of the Eating Disorder Examination was used
      to assess eating disorder psychopathology. Parental psychopathology was measured
      using the Symptom Checklist-90; parenting behavior was assessed with the Ghent
      Parental Behavior Scale. RESULTS: Parental psychopathology was prevalent in 59.6%
      of mothers and 35.7% of fathers. Youngsters exceeding the cutoff for problem
      behavior ranged between 41.4 and 53.1%. Children's problem behavior was most
      associated with psychopathology in the mother (r=0.40 for Internalizing and
      r=0.37 for Externalizing; both P<0.01). The research findings further revealed
      that the effects of maternal psychopathology were partly mediated by a specific
      form of parenting behavior, namely Inconsistent discipline, although the effect
      was stronger for Externalizing behavior (explained variance: 10%) than for
      Internalizing behavior (explained variance: 4%). No evidence was found for a
      mediator effect from parenting behavior on the eating disorder symptoms of the
      obese youngsters. However, several direct relations emerged, suggesting a
      negative association between a child's eating disorder symptoms and Positive
      parenting behavior by the mother (r= -0.20 for Eating concern; r= -0.18 for
      Restraint eating; r= -0.16 for Shape concern; all P<0.05) as well as by the
      father (r= -0.25 for Eating concern; r= -0.25 for Weight concern; both P<0.01; r=
      -0.21 for Shape concern; P<0.05). DISCUSSION: Parental characteristics were
      associated with psychological problems in obese youngsters, not only in a direct
      way but also indirectly. The effects were partly mediated by a particular
      ineffective parenting style, namely inconsistent discipline on the part of the
      mother. Pediatric obesity treatments should focus more on parenting behaviors and
      parental characteristics.

PMID- 16607385
TI  - Habitual physical activity and sedentary behaviour in a clinical sample of obese
      children.
AB  - OBJECTIVE: To objectively measure habitual physical activity and sedentary
      behaviour in a clinical sample of obese children and to compare with age- and sex
      matched non-obese controls. DESIGN: Pairwise comparison of obese children matched
      for age and gender with non-obese controls. SUBJECTS: A total of 116 obese
      children (body mass index (BMI)> or =98th centile) and 53 non-obese control
      children (BMI<85th centile). Controls were matched with 53 of the obese children
      (mean age 8.6, s.d. 2.0 years; 25 M and 28 F). MEASUREMENT: Habitual physical
      activity and sedentary behaviour were measured over a 7-day period using CSA
      accelerometers. Total physical activity (mean accelerometry count per minute
      (c.p.m.)), percentage of monitored time in sedentary behaviour, light and
      moderate to vigorous intensity physical activity (MVPA) were compared. RESULTS:
      Obese children (n=116) spent on average 80.4% of their monitored time in
      sedentary behaviour and 2.5% of their monitored time in MVPA. Total activity
      (mean c.p.m.) was significantly higher in the non-obese group (n=53) than the
      obese group (n=53), 729 vs 648 c.p.m.; 95% confidence interval (CI) 7, 155. Time
      spent in sedentary behaviour averaged 80.9% (s.d. 6.6) in the obese group and
      79.3% (s.d. 6.2) in the non-obese group, with no significant between-group
      difference (95% CI -3.9, 0.6). Light intensity activity was similar in the obese
      and non-obese groups (15.9 vs 17.3%; 95% CI -0.3, 3.0). Participation in MVPA was
      significantly higher in the non-obese vs obese group (3.9 vs 2.4%; 95% CI 0.6,
      2.0). CONCLUSION: This study supports the hypothesis that a clinical sample of
      obese children is less physically active than non-obese children, although the
      difference in total activity and MVPA between the groups was small.

PMID- 16607386
TI  - Socio-economic status and abdominal obesity among Finnish adults from 1992 to
      2002.
AB  - OBJECTIVE: To examine 10-year changes in waist circumference (WC) and identify
      socio-economic groups having higher WC than expected by their body mass index
      (BMI). DESIGN: Population based cross-sectional surveys carried out in four
      regions of Finland in 1992, 1997 and 2002. SUBJECTS: A total of 9026 women and
      8173 men, aged 25-64 years. MEASUREMENTS: Waist circumference, BMI, socio
      economic indicators (education, household income, employment status, marital
      status) and health behaviors (smoking, alcohol use, physical activity). RESULTS:
      In 2002, women had about 2.7 cm and men about 1.0 cm higher WC than subjects 10
      years previously. Waist circumference increased more than BMI among women,
      especially among unemployed women. Higher WC among non-employed women was not
      explained by socio-economic indicators or health behaviors. Among men, smaller WC
      was associated with lower socio-economic status. However, associations partly
      disappeared after adjustment for health behaviors including physical activity at
      work. CONCLUSION: Socio-economic patterning of WC is divergent and gender
      specific. More attention should be paid to increasing waistlines among women.

PMID- 16607387
TI  - A possible impact of the neuroD2 transcription factor on the development of drug
      abusing behavior.

PMID- 16607388
TI  - Expression and function of human steroid receptor RNA activator in prostate
      cancer cells: role of endogenous hSRA protein in androgen receptor-mediated
      transcription.
AB  - Steroid receptor RNA activator (SRA) was first isolated as a steroid receptor co
      activator that functioned as an RNA transcript. Later, we demonstrated that SRA
      needs to be translated in order to co-activate androgen receptor (AR). Here, we
      showed that three isoforms of human SRA enhanced AR activities. Small interfering
      RNA against SRA suppressed AR activities in PC-3 cells transfected with pSG5AR
      and in LNCaP cells that have an endogenous mutated-AR. Western blot showed that
      SRA protein was expressed at a higher level in PC-3 than in LNCaP cells,
      suggesting that SRA may be related to hormone-independent growth of prostate
      cancer.

PMID- 16607389
TI  - From inhibitor to drug: mind the gap!

PMID- 16607390
TI  - Thou shalt not clone. An ethical argument against the reproductive cloning of
      humans.

PMID- 16607391
TI  - Cloning in the media and popular culture. An analysis of German documentaries
      reveals beliefs and prejudices that are common elsewhere.

PMID- 16607392
TI  - Racial medicine: here to stay? The success of the International HapMap Project
      and other initiatives may help to overcome racial profiling in medicine, but old
      habits die hard.

PMID- 16607393
TI  - Into the fold. Advances in technology and algorithms facilitate great strides in
      protein structure prediction.

PMID- 16607395
TI  - An editor controlled by transcription.

PMID- 16607396
TI  - The role of glutathione in disulphide bond formation and endoplasmic-reticulum
      generated oxidative stress.
AB  - Glutathione is a ubiquitous molecule found in all parts of the cell where it
      fulfils a range of functions from detoxification to protection from oxidative
      damage. It provides the main redox buffer for cells and as such has been
      implicated in the formation of native disulphide bonds. However, the discovery of
      the enzyme Ero1 has called into question the exact role of glutathione in this
      process. In this review, we discuss the arguments for and against a role for
      glutathione in facilitating disulphide-bond formation and consider its role in
      protecting the cell from endoplasmic-reticulum-generated oxidative stress.

PMID- 16607397
TI  - Catalytic and mechanical cycles in F-ATP synthases. Fourth in the Cycles Review
      Series.
AB  - Cycles have a profound role in cellular life at all levels of organization. Well
      known cycles in cell metabolism include the tricarboxylic acid and the urea
      cycle, in which a specific carrier substrate undergoes a sequence of chemical
      transformations and is regenerated at the end. Other examples include the
      interconversions of cofactors, such as NADH or ATP, which are present in the cell
      in limiting amounts and have to be recycled effectively for metabolism to
      continue. Every living cell performs a rapid turnover of ATP to ADP to fulfil
      various energetic demands and effectively regenerates the ATP from ADP in an
      energy-consuming process. The turnover of the ATP cycle is impressive; a human
      uses about its body weight in ATP per day. Enzymes perform catalytic reaction
      cycles in which they undergo several chemical and physical transformations before
      they are converted back to their original states. The ubiquitous F1F(o) ATP
      synthase is of particular interest not only because of its biological importance,
      but also owing to its unique rotational mechanism. Here, we give an overview of
      the membrane-embedded F(o) sector, particularly with respect to the recent
      crystal structure of the c ring from Ilyobacter tartaricus, and summarize current
      hypotheses for the mechanism by which rotation of the c ring is generated.

PMID- 16607398
TI  - High-throughput RNAi screening in cultured cells: a user's guide.
AB  - RNA interference has re-energized the field of functional genomics by enabling
      genome-scale loss-of-function screens in cultured cells. Looking back on the
      lessons that have been learned from the first wave of technology developments and
      applications in this exciting field, we provide both a user's guide for newcomers
      to the field and a detailed examination of some more complex issues, particularly
      concerning optimization and quality control, for more advanced users. From a
      discussion of cell lines, screening paradigms, reagent types and read-out
      methodologies, we explore in particular the complexities of designing optimal
      controls and normalization strategies for these challenging but extremely
      powerful studies.

PMID- 16607399
TI  - D'Arcy Thompson and the theory of transformations.
AB  - D'Arcy Thompson was a biologist, a mathematician and a classicist. His writing
      was great literature as well as great science. He is primarily known for a single
      book--On Growth and Form--and indeed for a single chapter within it, on his
      'theory of transformations', which shows how the differences between the forms of
      related species can be represented geometrically. This theory cries out for
      causal explanation, which is something the great man eschewed. Perhaps the time
      is close when comparative developmental genetics will be able to provide such an
      explanation.

PMID- 16607400
TI  - Neuroscience and education: from research to practice?
AB  - Cognitive neuroscience is making rapid strides in areas highly relevant to
      education. However, there is a gulf between current science and direct classroom
      applications. Most scientists would argue that filling the gulf is premature.
      Nevertheless, at present, teachers are at the receiving end of numerous 'brain
      based learning' packages. Some of these contain alarming amounts of
      misinformation, yet such packages are being used in many schools. What, if
      anything, can neuroscientists do to help good neuroscience into education?

PMID- 16607404
TI  - Correspondence of George Newman (1870-1948) during his years as school boy,
      medical student and recent graduate (1880-1907).
AB  - The correspondence is reported of Sir George Newman, the first Chief Medical
      Officer of the United Kingdom, during his school and university education.
      Extracts are included of this hitherto unpublished correspondence with his family
      members. His conception of idealistic service to the community, first enunciated
      in his school days, was expanded by practical action as a medical student among
      the urban poor of the Cowgate, Edinburgh. The correspondence reveals his
      unmarried maternal aunt as the person who influenced him most.

PMID- 16607405
TI  - Louis Stromeyer (1804-76): German orthopaedic and military surgeon and his links
      with Britain.
AB  - Louis Stromeyer was a pioneer of orthopaedic surgery and military medicine in
      Germany. The 200th anniversary of his birth was celebrated on 6 March 2004. He
      was much admired in Britain, which he visited on three occasions and where he met
      many of the country's leading surgeons. He was a friend and colleague of the
      London surgeon W J Little (1810-94), whose clubfoot he corrected by the operation
      he developed, and which Little introduced to Britain: subcutaneous tenotomy. A
      bibliography of Stromeyer's publications is appended.

PMID- 16607406
TI  - Dr David Maclagan (1785-1865): distinguished Military Surgeon, President of both
      the Royal College of Surgeons and Royal College Physicians of Edinburgh, founder
      of a medical and military dynasty.
AB  - Dr David Maclagan studied medicine in Edinburgh, obtaining the LRCS Edin Diploma
      in 1804 and graduating with the MD degree in 1805. Because he was too young to
      enter the army, he spent a year in London, principally at St. George's Hospital,
      and he gained the MRCS England Diploma in 1807. Then he entered the army as an
      Assistant Surgeon associated with the 91st Foot Regiment. He served at Walcheren
      in 1809 and in the Peninsula. Later he was seconded as a Surgeon-Major to the 9th
      Portuguese Brigade. After his promotion to Physician to the Forces, he
      superintended the hospital arrangements of the Portuguese Army. Between 1811 and
      1814 he sent a series of letters, principally to his wife, giving his personal
      impressions of his life in the war zone. He also maintained two personal diaries
      that nominally detailed his activities in the Peninsula between 1812 and 1813.
      After the end of the fighting he was put on half-pay and returned to Edinburgh.
      Then he gained the Fellowship of the Royal College of Surgeons of Edinburgh in
      1816 and was appointed a Surgeon to the New Town Dispensary. After he established
      himself in private practice in Edinburgh he became the Honorary Consulting
      Surgeon to the Dispensary until shortly before his death. He was elected
      President of the Edinburgh College of Surgeons in 1826-27. He became a Fellow of
      the Royal College of Physicians of Edinburgh in 1848, and was elected its
      President in 1856-57. He founded an important medical and military dynasty. Three
      of his sons joined the medical profession and four served in the army. One of his
      sons was appointed Archbishop of York. His eldest son followed in his father's
      footsteps and was also President of both Royal Colleges, of Surgeons and
      Physicians, in Edinburgh. His widow, Jane, and his seven sons survived him.

PMID- 16607407
TI  - Thomas Vicary, barber-surgeon.
AB  - An Act of Parliament in 1540 uniting the barbers and surgeons to form the Barber
      Surgeons' Company represented an important foundation stone towards better
      surgery in England. Thomas Vicary, who played a pivotal role in promoting this
      union, was a leading surgeon in London in the middle of the 16th century. While
      Vicary made no direct contribution to surgical knowledge, he should be remembered
      primarily as one who contributed much towards the early organization and teaching
      of surgery and to the consequent benefits that flowed from this improvement.

PMID- 16607408
TI  - The practice of euthanasia at the highest level of society: the Lords Dawson
      (1864-1945) and Horder (1871-1955).
AB  - The intimate involvement of Lord Dawson of Penn in the terminal illness of King
      George V in 1936 was highlighted 50 years later when his personal papers were
      released for perusal in the public arena. A popular jingle of the time relating
      to Dawson was recalled in a leading article in The Times newspaper in 1986.
      Knowing that a similar rhyme was in circulation involving Lord Horder of Ashford,
      I wrote to his son in order to verify exactly what this was; his reply is
      reproduced in this article.

PMID- 16607409
TI  - Sir Francis Walshe, MD FRS (1885-1973).
AB  - Born in Ireland, Francis Martin Rouse Walshe studied medicine at University
      College Hospital. He subsequently practised there and at the National Hospital,
      Queen Square, London. Early associations with Wilfred Trotter and Sir Victor
      Horsley encouraged his career in Neurology. Walshe pioneered the descriptive
      analysis of human reflexes in physiological terms. His flare and outstanding
      brilliance were rewarded when he was appointed Physician to the National
      Hospital, Queen Square in 1921 and at University College Hospital in 1924. He
      published, mainly in Brain (which he edited for many years), weighty papers on
      the function of the cerebral cortex in relation to movements, and on neural
      physiology. Walshe is also remembered for his powers of literacy and stringent
      scientific criticism, which he often displayed with magnificent panache.

PMID- 16607410
TI  - David Livingstone's uvulectomy.
AB  - In April 1852 in Cape Town, South Africa, Dr David Livingstone, then 39 years of
      age and yet to commence the explorations of Africa which would bring him to
      public attention, underwent the surgical procedure of uvulectomy. This article
      reviews the history of Livingstone's uvulectomy and its indications and outcome,
      as documented by his own writings. The practice of uvulectomy in indigenous
      African societies and some contemporary ideas about uvulectomy are also
      considered in order to try to ascertain why Livingstone elected to undergo this
      procedure.

PMID- 16607411
TI  - The Women's Hospital Corps: forgotten surgeons of the First World War.
AB  - Under the leadership of the former militant suffragists Flora Murray and Louisa
      Garrett Anderson, a group of women doctors calling themselves the Women's
      Hospital Corps (WHC) successfully ran two military hospitals in France from
      September 1914 to January 1915. In 1915 the War Office invited them to run a
      military hospital in London where large numbers of new beds were being created.
      It gave them former workhouse premises in Covent Garden, which they transformed
      into a 573-bed hospital, staffed and administered entirely by women. The Endell
      Street Military Hospital, the first hospital in the UK established for men by
      medical women, was open from May 1915 to December 1919; in that time, its doctors
      saw 26,000 patients and performed over 7000 major operations. A key feminist
      organization of the First War, the WHC has largely been forgotten, partly because
      of its relatively small size and partly because of its anomalous status as a
      female-run hospital under the direct patronage of the War Office.

PMID- 16607412
TI  - Oliver St John Gogarty, MD (1878-1957): quintessential Irish Literary Renaissance
      figure.
AB  - Oliver St John Gogarty (1878-1957) was a quintessential figure of the Irish
      literary renaissance. He was a successful surgeon, accomplished lyric poet, a man
      of letters, a senator in the first Irish Free State and a celebrated wit. While
      pursuing a successful career in ear, nose, and throat (ENT) surgery, Gogarty
      served a brief, nearly lethal term in politics. He devoted the last several years
      of his life to a remarkably versatile literary career, the spectrum of his
      creativity including elegant lyric poetry, autobiographies, biographies, essays,
      novels and parodies.

PMID- 16607414
TI  - Health sector charter needs rethink.

PMID- 16607415
TI  - Sexual behaviour and SAMA.

PMID- 16607416
TI  - Mirena and ectopic pregnancy -- a diagnostic challenge.

PMID- 16607417
TI  - GCP accreditation -- a worthwhile investment?

PMID- 16607418
TI  - NOAH rescue AIDS orphans.

PMID- 16607419
TI  - Gay 'militant' stays bloody minded.

PMID- 16607420
TI  - Lack of capacity devitalizing SA' hospitals.

PMID- 16607421
TI  - New blood test fails to set hearts racing.

PMID- 16607423
TI  - Community service doctors in Limpopo province.

PMID- 16607424
TI  - The threat of a new influenza pandemic -- are we doing enough?

PMID- 16607425
TI  - Cancer of the oesophagus -- quo vadis?

PMID- 16607426
TI  - Genetic testing for spinal muscular atrophy (SMA) in South Africa.

PMID- 16607427
TI  - Paediatric HIV disclosure in South Africa -- caregivers' perspectives on
      discussing HIV with infected children.

PMID- 16607428
TI  - HIV seroconversion during pregnancy in the Tygerberg region of Cape Town.

PMID- 16607429
TI  - Notification of rheumatic fever in South Africa -- evidence for underreporting by
      health care professionals and administrators.
AB  - OBJECTIVE: To determine whether under-reporting of rheumatic fever occurs at
      hospital, municipal, provincial and national levels of the South African health
      system. BACKGROUND: Information on the incidence of rheumatic fever (RF) and the
      prevalence of rheumatic heart disease (RHD) is required for the prevention of
      valvular heart disease in developing countries. In South Africa, RF was made a
      notifiable condition in 1989. It has recently been suggested that the reporting
      of RF cases may be incomplete, possibly because of underreporting by health care
      professionals and deficient administration of the disease notification system in
      South Africa. METHOD AND RESULTS: We assessed whether underreporting of RF cases
      occurs by comparing the numbers of RF cases reported per year at hospital,
      municipal, provincial and national levels from 1990 to 2004. There was a fall in
      the number of RF cases reported per year at national and provincial level over
      the 15 years of observation. A detailed analysis of the number of RF cases
      reported at hospital, municipal and provincial level for a 5-year period showed
      that more cases were diagnosed in one hospital (serving a smaller population)
      than were captured at municipal and provincial level (serving a larger
      population), suggesting underreporting by health care professionals. There were
      discrepancies in the number of cases reported at municipal, provincial and
      national level, suggesting poor administration of the notification system.
      CONCLUSION: There appears to be underreporting of RF cases by health care
      professionals, and poor administration of the RF notification system. Health care
      professionals need to be educated about the statutory requirement to notify all
      RF cases in South Africa. An effective national disease notification system is
      required.

PMID- 16607430
TI  - Self-induced vomiting -- risk for oesophageal cancer?
AB  - BACKGROUND: Chronic inflammation of the oesophagus is considered a precursor
      condition for the development of oesophageal cancer. Identification of the causes
      of chronic oesophageal irritation is therefore relevant in developing preventive
      measures. Self-induced vomiting is a cultural practice among the black population
      of South Africa, particularly those living in the Transkei, a region reported to
      have one of the highest incidences of oesophageal cancer worldwide. METHODS: We
      retrospectively examined the association between the practice of self-induced
      vomiting and the development of cytological features of inflammation in 478 self
      selected subjects living in Transkei who underwent early screening for
      oesophageal cancer. Screening involved brush biopsy, cytological investigation
      and a questionnaire interview. RESULTS: The prevalence of self-induced vomiting
      was 80.5% and 79.1% in males and females, respectively, and this was stable
      across all ages. Furthermore, self-induced vomiting was found to be significantly
      and independently associated with oesophageal chronic inflammation (odds ratio
      1.83, 95% confidence interval: 1.13 - 2.96, p = 0.013). CONCLUSION: While the
      association between the cultural practice of self-induced vomiting and
      oesophageal cancer has previously been hypothesised, this is the first study to
      report on an association between this practice and oesophageal chronic
      inflammation. Further studies that take into account the method used, frequency
      and duration of vomiting, age of commencement and fasting state of subjects
      practicing self-induced vomiting coupled with accurate indicators of inflammation
      are needed to elucidate the role of self-induced vomiting in oesophageal
      pathogenesis.

PMID- 16607431
TI  - Oro-facial trauma in child abuse fatalities.
AB  - Many children die as a result of abuse and neglect each year. Early recognition
      and effective intervention are crucial factors in the fight against this. Child
      mortality rates increased in South Africa between 1998 and 2004, with child abuse
      deaths constituting part of these statistics. Autopsies on children who have died
      of unnatural causes are often not specific as to the possibility of child abuse.
      This article presents the extra-oral and intra-oral signs of child abuse from a
      study of the autopsies of child mortality cases seen at Salt River Medico-Legal
      Laboratory in Cape Town from 1998 to 2004 with reference to the South African
      child mortality rates.

PMID- 16607432
TI  - Unsuspected glucose abnormalities in patients with coronary artery disease.
AB  - OBJECTIVES: To compare the ability of fasting glucose, glycosylated haemoglobin (
      HbA(1c)), the American Diabetic Association (ADA) score and measures of the
      metabolic syndrome (waist circumference, high-density lipoprotein (HDL), and
      triglycerides) in predicting an initial diagnosis of diabetes mellitus or
      abnormal glucose tolerance based on the World Health Organization (WHO) criteria.
      DESIGN: A cross-sectional, diagnostic study was undertaken of 120 patients
      admitted to the cardiology wards of Pretoria Academic Hospital for elective
      coronary angiographic studies. MAIN OUTCOME MEASURES: All subjects underwent a
      modified glucose tolerance test whereby fasting and 2-hour post glucose (75 g)
      plasma glucose levels were measured. Using the revised WHO criteria, the overall
      incidence of diabetes was found to be 11.7% (95% confidence interval (CI): 6.5 -
      19) and the overall incidence of abnormal glucose tolerance was 46% (CI: 37 -
      55). RESULTS: In univariate analysis for the diagnosis of diabetes, HbA(1c) (p <
      0.05) yielded the largest area (0.76) under the receiver operating characteristic
      (ROC) curve, with a sensitivity of 21%, specificity of 99%, positive predictive
      value (PPV) of 75% and negative predictive value (NPV) of 91%. For the prediction
      of abnormal glucose tolerance, applying multivariate analysis using a logistic
      regression model, the combination of age, ethnic group, serum HDL, serum
      triglycerides and HbA(1c) yielded an area under the ROC curve of 0.79,
      sensitivity of 66%, specificity of 80%, PPV of 76% and a NPV of 71%. CONCLUSION:
      Most subjects with diabetes mellitus (9 of 14) would not have been detected if a
      2-hour oral glucose tolerance test had not been done. Addition of either HbA(1c)
      or lipid parameters to the model of age and ethnic group were similar in
      predicting abnormal glucose tolerance.

PMID- 16607433
TI  - Continuing communicable disease burden in Eritrea.
AB  - BACKGROUND AND METHODS: A retrospective study of the national health profile of
      Eritreans, focusing on acute respiratory tract infection (ARTI), tuberculosis
      (TB), diarrhoea, sexually transmitted diseases (STDs) and HIV/AIDS, was done on
      data from 1998 to 2003 through a health information management system. Records
      were included for patients of all ages receiving outpatient and inpatient
      hospital services during the study period. All incidence rates were given as
      cases per 100,000 population. RESULTS: The incidence of ARTI increased from 6,500
      cases per annum in 1998 to 8 500 in 2003, representing a 30% increase. Diarrhoea
      rates remained unchanged, averaging 3,000 cases. For both ARTI and diarrhoea,
      rates were at least 3 times higher in children under 5 years of age than in those
      over 5 years of age. The incidences of TB and STDs decreased from 370 and 220 in
      1998 to 170 and 80 in 2003, respectively. HIV/AIDS incidence increased from 40 in
      1998 to 65 in 2003, reflecting a 60% increase. The case fatality rates (CFRs) for
      HIV/AIDS and TB were 12% and 2% in 1998, increasing to 14% and 3%, respectively,
      in 2001. The CFR for ARTI and diarrhea remained low at 0.3%. CFRs were higher in
      children under 5 years than in those over 5 years for all the diseases but rates
      declined consistently, probably reflecting the positive impact of the
      introduction of the integrated management of childhood illness (IMCI). Although
      the incidence rate of HIV/AIDS was relatively low compared with rates for TB,
      ARTI and diarrhoea, the HIV/AIDS CFR was relatively high, posing a threat to the
      gains made in control of infectious diseases. The disease burden from TB and STDs
      declined over the 6-year study period, while that from ARTI and HIV/AIDS
      increased. Consequently the overall disease burden from communicable diseases
      remained unchanged over the study period.

PMID- 16607434
TI  - Antibiotic susceptibility patterns of Neisseria gonorrhoeae isolates in Port
      Elizabeth.
AB  - OBJECTIVE: To survey the antibiotic susceptibility of Neisseria gonorrhoeae
      isolates. DESIGN: This was a cohort analytical study. SETTING: Three clinics
      serving different areas in Port Elizabeth. Outcome measures. Prevalence of
      antibiotic-resistant N. gonorrhoeae isolates. RESULTS: Twenty-one of the 35
      isolates (60%) were resistant to ciprofloxacin, while 28 (80%) showed resistance
      to erythromycin, 17 (48.6%) to penicillin, 3 (8.6%) to doxycycline, 11 (31.4%) to
      spectinomycin and 33 (94.3%) to tetracycline. CONCLUSION: To ensure effective
      treatment of gonorrhoea, continued surveillance of antimicrobial susceptibility
      is necessary.

PMID- 16607436
TI  - Welcome address: Rheumatic heart disease is a neglected disease of poverty
      requiring a multisectoral approach for control and eradication.

PMID- 16607437
TI  - Frequency and severity of rheumatic heart disease in the catchment area of
      Gauteng hospitals, 1993-1995.
AB  - OBJECTIVE: Identification of frequency and severity of rheumatic fever/rheumatic
      heart disease (RF/RHD) in the catchment area of Gauteng hospitals. DESIGN: A
      retrospective descriptive analysis using hospital-based computer databases.
      SETTING: Helen Joseph, Chris Hani Baragwanath and Johannesburg General hospitals,
      Gauteng, South Africa. SUBJECTS: Three hundred and twelve of 493 (63%) paediatric
      RF/RHD patients with documented addresses seen from 1993 to 1995. METHODS: A
      proportional analysis, with the total congenital heart disease (CHD) patients
      seen in an area as the denominator, was employed to identify areas with prevalent
      and/or severe RF/RHD. Severe disease was defined as that requiring surgery or
      balloon valvuloplasty. RESULTS: 32.7% of RF/RHD patients came from outside
      Gauteng, and 70.2% of those seen at Chris Hani Baragwanath Hospital were not from
      Soweto. KwaZulu-Natal, Northern Province, Mpumalanga and Evaton had a
      significantly higher-than-expected ratio of RHD/CHD patients and were identified
      as priority areas at high risk for RHD. Gauteng and some Johannesburg suburbs had
      a significantly lower-than-expected ratio and therefore had a relatively low risk
      for RHD. 32.9% of RHD patients had severe disease. The severity rate for Gauteng
      residents was 34.8% and for non-Gauteng residents 51%. Significantly more severe
      cases than expected came from KwaZulu-Natal, Northern Province, Mpumalanga and
      Gauteng south. Significantly fewer severe RHID patients than expected came from
      Gauteng, especially Gauteng centre. CONCLUSIONS: A high frequency of RF/RHD and
      severe disease was recorded in patients living in KwaZulu-Natal, Northern
      Province and Mpumalanga.

PMID- 16607438
TI  - Management of patients with rheumatic fever and rheumatic heart disease in
      Nigeria--need for a national system of primary, secondary and tertiary
      prevention.

PMID- 16607439
TI  - Protocols for antibiotic use in primary and secondary prevention of rheumatic
      fever.

PMID- 16607440
TI  - Towards a uniform plan for the control of rheumatic fever and rheumatic heart
      disease in Africa--the Awareness Surveillance Advocacy Prevention (A.S.A.P.)
      Programme.

PMID- 16607444
TI  - Use of diagnosis-based risk adjustment models to predict individual health care
      expenditure under the National Health Insurance system in Taiwan.
AB  - BACKGROUND AND PURPOSE: Diagnostic information has been extensively studied and
      employed in the prediction of risk adjusted capitation payments in some
      countries. Nevertheless, few studies have been dedicated to the development of
      diagnosis-based risk adjusters in Taiwan. The purposes of this study were to
      develop outpatient diagnosis-based risk adjusters for a model of Taiwan's
      National Health Insurance (NHI) system and to evaluate the predictability of the
      risk adjustment models generated utilizing these adjusters. METHODS: Using a 2%
      random sample of 371,620 NHI enrollees, 5 risk adjustment models--i.e.,
      demographic, inpatient diagnostic information outpatient diagnostic information,
      full diagnostic information, and prior utilization models--were evaluated with
      respect to predictive R2 and predictive ratios. While inpatient diagnosis-based
      risk adjusters were borrowed from previous research, outpatient diagnosis-based
      risk adjusters, referred to as Taiwan Ambulatory Spending Groups (TASGs), were
      developed based on 1996 claims data. RESULTS: The values of predictive R2 for the
      5 risk adjustment models showed that the inclusion of outpatient diagnostic
      information considerably improved the predictability of the risk adjustment
      models for Taiwan's NHI system. Moreover, the predictive ratios revealed that the
      full diagnostic information model would reimburse different risk subgroups more
      fairly than the demographic, inpatient diagnostic information, and outpatient
      diagnostic information models and also outperform the prior utilization model
      with respect to disease risk groups. CONCLUSIONS: The risk adjustment model
      including the TASG risk adjusters can significantly improve predictability and
      can be employed to assess the NHI's current and proposed reform measures.

PMID- 16607445
TI  - Acute renal failure in patients with severe acute respiratory syndrome.
AB  - BACKGROUND AND PURPOSE: Severe acute respiratory syndrome (SARS) is caused by a
      new coronavirus, and results in respiratory failure. Acute renal failure (ARF)
      may also occur and/or complicate the disease course, however, its incidence,
      causes and impact in SARS patients are not known. METHODS: ARF patients were
      identified from a total of 78 (33 men and 45 women) probable SARS cases admitted
      to a single hospital. The clinical features of patients with ARF were
      characterized, and the etiologies analyzed. RESULTS: Patients were assigned to
      ARF (n = 13; 17%) and non-ARF groups (n = 65). Patients with ARF were older than
      their non-ARF counterparts. ARF developed 7.2 +/- 4.3 days after admission. The
      incidence of ARF was higher in males (77% vs 35%; p < 0.05). Comorbidities of
      diabetes and heart failure were more common in patients who developed ARF (38% vs
      6%, p < 0.01 and 38% vs 2%, p < 0.001, respectively) and the incidence of
      respiratory failure (85% vs 26%, p < 0.001) and mortality (77% vs 8%, p < 0.001)
      were also higher. Multiple organ system failure usually accompanied ARF.
      Hypotension (77%) caused by nosocomial infections, gastrointestinal bleeding, or
      SARS per se, and rhabdomyolysis (43%) was associated with ARF in addition to pre
      renal factors. Five patients in the ARF group and 1 female patient with end-stage
      renal failure underwent renal replacement therapy during hospitalization;
      however, both eventually died. Of the 16 medical staff performing renal
      replacement therapy, none was subsequently infected with SARS coronavirus.
      CONCLUSIONS: Development of ARF during the disease course in SARS patients is
      associated with catastrophic outcome. The cause of ARF in SARS patients is often
      associated with pre-renal factors, hypotension, rhabdomyolysis, and previous
      comorbidities including diabetes and old age. Universal precautions to prevent
      viral transmission are mandatory for medical staff performing renal replacement
      therapy.

PMID- 16607446
TI  - Lymphadenitis caused by non-tuberculous mycobacteria in a university hospital in
      Taiwan: predominance of rapidly growing mycobacteria and high recurrence rate.
AB  - BACKGROUND AND PURPOSE: Lymphadenitis is the most common manifestation of
      infection due to non-tuberculous mycobacteria (NTM) in otherwise healthy
      children. This disease is rare in adults and its geographic variations in
      etiology and clinical manifestations remain unclear. The aim of this study was to
      describe the etiology, clinical presentation, treatment, and outcome of NTM
      lymphadenitis. METHODS: Medical records of patients with culture-proven NTM
      lymphadenitis treated at a university hospital in Taiwan from January 1997
      through December 2004 were retrospectively reviewed. RESULTS: In total, 12
      patients with NTM lymphadenitis were identified, including 6 males and 7 adults
      (> or = 16 years). The majority (83%) of patients presented with an enlarged
      palpable mass and 9 (75%) had preceding constitutional symptoms. The most common
      site of lymphadenitis was the cervical area (83%) and 8 patients (75%) had
      multiple lymph node involvement. Rapidly growing mycobacteria (RGM) accounted for
      75% of the etiology of NTM lymphadenitis, followed by Mycobacterium avium complex
      (MAC) [2 patients]. A high recurrence rate (42%) after primary treatment was
      noted among those patients who received clarithromycin-containing regimens for a
      median of 6 months. CONCLUSIONS: This study found that both previously healthy
      children and adults were susceptible to NTM lymphadenitis. RGM was the most
      common etiology rather than MAC among NTM species causing lymphadenitis.
      Inadequate surgical excision of the diseased lymph nodes and insufficient
      coverage of antimycobacterial therapy both contributed to the high recurrence
      rate.

PMID- 16607447
TI  - Clinicopathological characteristics and prognosis of patients with small
      intestinal stromal tumors.
AB  - BACKGROUND AND PURPOSE: Gastrointestinal stromal tumors (GISTs) involving the
      small intestine are less common than those involving the stomach, and data on
      small intestinal stromal tumors (SISTs) are more limited. This study investigated
      the clinicopathological characteristics and prognostic factors of SISTs and
      compared them with those of gastric stromal tumors (GSTs). METHODS: A total of 82
      surgically resected and pathologically diagnosed smooth muscle tumors of small
      bowel in patients treated from January 1986 to December 2000 were included.
      Immunohistochemical studies were performed on these tumors with antibodies of
      CD117, CD34, smooth muscle actin (SMA), desmin and S-100. The results were
      analyzed and compared with 74 cases of GSTs diagnosed and treated from January
      1986 to December 1997. RESULTS: Among the 82 small intestine tumors, 71 were
      CD117-positive (86.6%) and were classified as SISTs. Of the 71 SISTs, 70.4% were
      immunoreactive to CD34, 88.7% to SMA, 46.5% to S-100, but none to desmin.
      Survival analysis demonstrated that tumor size < 5 cm (p = 0.021), mitosis number
      < 5/50 high-power field (p < 0.001), SMA-positive (p = 0.027), non-epithelioid
      cell type (p = 0.005) and tumor with skeinoid fibers (p = 0.010) predicted longer
      disease-free survival after operation. Multivariate analysis revealed that
      mitotic number (p = 0.001), cell morphology (p = 0.031) and tumor size (p =
      0.004) were independent prognostic factors. In comparison to GSTs, SISTs
      exhibited significantly lower rates of CD34, but significantly higher rates of
      SMA and S-100 immunoreactivity. CONCLUSIONS: SISTs exhibited a different
      immunophenotype from GSTs. SMA reactivity is a predictor of benign clinical
      behavior in SISTs. Tumor mitotic numbers, tumor size, and cell type were
      independent prognostic factors for patients with SISTs after operation.

PMID- 16607448
TI  - Pain control in Taiwanese patients with cancer: a multicenter, patient-oriented
      survey.
AB  - BACKGROUND AND PURPOSE: Under-treatment of cancer pain remains a common problem
      in Taiwan. Prior studies were mainly in hospitalized patients and limited to one
      or a few centers. This prospective, multicenter, patient-focused survey assessed
      the prevalence, severity and management of cancer pain in oncology clinic
      outpatients. Analgesic use and patient satisfaction with analgesic therapy were
      also evaluated. METHODS: A total of 480 Taiwanese patients receiving outpatient
      treatment at 15 different outpatient clinics were included in this study. There
      were 263 males and 217 females with a mean age of 62.13 years. Patients completed
      a 4-question survey about the presence or absence of pain, pain severity,
      analgesic therapy, and satisfaction or dissatisfaction with the degree of
      analgesia. RESULTS: Pain was reported by 257 patients (54%). Severe pain was
      reported by 35% and moderate pain by 35.4% of patients. Only 149 of the patients
      who reported pain (58%) were receiving analgesic medication, with a roughly
      equivalent number of males and females. Most (95 of 149, 64%) reported being
      satisfied or very satisfied with pain control although this percentage was higher
      among males than females (68.23% vs 57.8%). Major variation in the results was
      noted among study centers. CONCLUSIONS: The results of this survey of Taiwanese
      outpatients with cancer confirm that cancer pain is under-treated in oncology
      clinics in Taiwan. A major goal of cancer management is to achieve high rates of
      patient satisfaction and compliance with treatment which maintains or improves
      quality of life.

PMID- 16607449
TI  - Estrogen receptor beta is not increasingly expressed in leiomyoma nodules which
      show no progressive enlargement in premenopausal women.
AB  - BACKGROUND AND PURPOSE: Studies on the expression of estrogen receptors (ERs) in
      uterine leiomyomata have yielded conflicting results. A controlled study focusing
      on leiomyomal nodules with same clinical presentations and hormonal milieu was
      conducted to investigate the role of ER beta (ERbeta) on leiomyomal growth.
      METHODS: Thirty pairs of leiomyomal and myometrial tissues were included in the
      study. The specimens were obtained from 30 premenopausal women (40-45 years old)
      with parity 2, and were sampled during the proliferative menstrual phase. All of
      the leiomyomal nodules were unifocal, medium sized (4-5 cm), intramurally
      located, and without progressive enlargement for 6 months. The expressions of
      ERbeta mRNA and protein in leiomyomata and their adjacent myometria were analyzed
      by reverse transcriptase-polymerase chain reaction and immunohistochemistry using
      ERbeta-specific antibody, respectively. ER alpha (ERalpha) was simultaneously
      studied using similar methods. The results were digitally quantified and compared
      with each other. RESULTS: All paired tissues (30/30, 100%) showed a higher
      ERalpha expression level (paired t test, p < 0.05). In most leiomyomal nodules
      (27/30, 90%), both ERbeta and ERalpha exhibited no differences in mRNA levels
      compared to their adjacent myometria (p > 0.05), but the ratio of ERbeta/ERalpha
      (expression index) was lower (p < 0.05) in leiomyomal tissue. Although the
      immunoreactivity scores for ERbeta were similar in paired tissues, more ERbeta
      positive cells were detected in myometrial specimens than in their leiomyoma
      counterparts (mean of 62% vs 56%). Furthermore, the distribution pattern of
      ERbeta in leiomyoma (nuclear and cytoplasmic) was different from that in the
      corresponding myometrium (nuclear). The lower ERbeta/ERalpha expression index in
      stationary leiomyoma suggests that the relative abundance of ERbeta and ERalpha,
      rather than their individual amounts, determines the existence and development of
      leiomyoma. CONCLUSIONS: This study demonstrated that in premenopausal women,
      ERbeta is not increasingly expressed in the leiomyomal nodules which show no
      progressive enlargement. The distinctive ERbeta-to-ERalpha ratio rather than
      their individual amounts, is associated with the stationary status of the
      leiomyomal nodule.

PMID- 16607450
TI  - Retinal nerve fiber layer thickness measured by optical coherence tomography and
      its correlation with visual field defects in early glaucoma.
AB  - BACKGROUND AND PURPOSE: To study the relationship between retinal nerve fiber
      layer (RNFL) thickness measured by optical coherence tomography (OCT) and visual
      field defects in early glaucomatous eyes and to study the diagnostic ability of
      OCT in distinguishing early glaucomatous eyes from normal eyes. METHODS: We
      studied 68 eyes from primary open-angle glaucoma patients with early visual field
      defect (mean deviation > -6 dB), and 94 normal eyes from healthy age- and gender-
      matched individuals. All participants underwent 3.4-mm diameter circular OCT
      scans and Humphrey 30-2 mode visual field testing. The average and segmental RNFL
      thickness values were compared between the 2 groups. The correlation between the
      mean deviation in the visual field examination and RNFL thickness was evaluated.
      The area under the receiver operating characteristic (ROC) curve was used to
      distinguish normal eyes from early glaucomatous eyes. RESULTS: There was a
      significant difference in RNFL thickness between the 2 groups based on the
      following parameters: average thickness; superior, inferior, and nasal quadrant
      thickness; and 1-7, 11, 12 o'clock hour segment thickness (p < 0.05). In the
      glaucoma group, superior and inferior quadrant thicknesses and average RNFL
      thickness significantly correlated with the visual field index (superior quadrant
      thickness, r = 0.36; inferior quadrant thickness, r = 0.32; average RNLF
      thickness, r = 0.35; p < 0.05). The average RNFL and inferior quadrant thickness
      of early glaucomatous eyes had the widest areas under the ROC curves (0.812 and
      0.793, respectively). CONCLUSIONS: Measurement of average and inferior quadrant
      RNFL thickness by OCT is useful in detecting early glaucomatous change.

PMID- 16607451
TI  - Evaluation of the changes in midfacial configuration after face mask therapy in
      skeletal Class III growing patients by morphometric analysis techniques.
AB  - BACKGROUND AND PURPOSE: The prevalence of Angle Class III malocclusion is
      relatively high in Taiwan. For children who suffer from maxillary retrognathia,
      face mask therapy is a promising treatment modality. The purpose of this study
      was to evaluate the changes in midfacial configuration after face mask therapy in
      skeletal Class III growing patients by morphometric analysis techniques. METHODS:
      Thirty children who had been treated with face masks were compared with a group
      of 30 gender-matched, age-matched, observation period-matched, and craniofacial
      configuration-matched subjects with untreated Class III malocclusions. Average
      geometries, scaled to an equivalent size, were generated by means of Procrustes
      analysis. Graphical analysis, utilizing thin-plate spline analysis and strain
      tensor methods, was performed for localization of differences in shape and size
      changes. Maximum and minimum principal extensions were drawn to express the
      directions of shape change. RESULTS: Maxillary protraction-induced changes
      resulted from a combination of both orthopedic and dental effects. A significant
      increase in size (7.7% to 9.9%) was noted at the supero-anterior region of the
      midfacial configuration (rhinion-orbitale-midpalatal point-anterior nasal spine)
      when subjected to an extraoral traction force; 7.7% to 12.1% of increase in size
      and 14.4% to 33.4% of change in shape were found at the anterior portion of the
      maxillary alveolar bone. The directions and amount of principal strain tensors
      could express the magnitudes and directions of morphological changes within the
      midfacial complex in an efficient way. CONCLUSIONS: We conclude that morphometric
      analysis techniques can be used to evaluate the changes in midfacial
      configuration after face mask therapy and can provide a valuable supplement for
      conventional cephalometric analysis.

PMID- 16607452
TI  - Massive subcutaneous emphysema following bronchoscopy-guided percutaneous
      dilatational tracheostomy.
AB  - Although percutaneous dilatational tracheostomy (PDT) has become a safe procedure
      for airway management in critically ill patients, this operation can be
      associated with serious life-threatening complications. Massive subcutaneous
      emphysema is an unusual and sometimes lethal complication which may extend the
      length of stay in the intensive care unit (ICU). We report 2 cases, including 1
      fatality, of massive subcutaneous emphysema without tracheal wall laceration that
      occurred in the ICU after elective bronchoscopy-guided Ciaglia Blue Rhino (Cook
      Critical Care, Bloomington, IL, USA) PDT. Our analysis of these cases suggested
      that PDT-related barotraumas and imperfect positioning of the fenestrated
      tracheostomy tube could be the possible mechanisms for the observed
      complications. In case 1, we reduced the ventilator pressure and prescribed
      bronchodilator to decrease the airway pressure and keep the airway patent. In
      case 2, the suggested approach was to check if the fenestration of tracheostomy
      tube was extraluminal or change to non-fenestrating cannulas. For diminishing the
      impact of PDT on respiratory mechanics, especially in patients with underlying
      lung diseases, we recommend introducing the bronchoscope only when needed,
      instead of keeping the bronchoscope in the airway throughout the PDT procedure
      and using forceps to create a larger stoma if the dilation procedure is not
      smooth.

PMID- 16607453
TI  - Accidental ingestion of Ecstasy in a toddler.
AB  - Toddlers who ingest the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA;
      'Ecstasy') are at particularly high risk of serious neurological and
      cardiovascular side effects. We report of a 20-month-old male toddler who
      accidentally ingested Ecstasy. He presented with fever and seizures, tachycardia,
      hypertension, and hyperthermia. Urine amphetamine level was 2111 ng/mL. Treatment
      included rapid cooling, hydration, and support measures. Vital signs were
      regularly monitored. His condition became stable on day 2 and urine amphetamine
      level returned to normal on day 3 of hospitalization. His behavior, activity, and
      appetite had returned to their usual levels upon follow-up at our outpatient
      clinic. The incidence of drug abuse with MDMA has increased dramatically over the
      last decade in developed countries. It can be expected that accidental Ecstasy
      poisoning in children will increase as well. This case illustrates the need to
      consider the possibility of accidental Ecstasy ingestion in the differential
      diagnosis of a child suffering from convulsions with fever.

PMID- 16607454
TI  - Streptococcus suis meningitis with ventriculoperitoneal shunt infection and
      spondylodiscitis.
AB  - Streptococcus suis is a zoonotic pathogen which causes meningitis, bacteremia,
      and endocarditis in pigs. Human infection is rare and often presents as
      meningitis with the sequela of permanent deafness and endocarditis. Previous
      cases were reported from pig-rearing countries such as Holland and Hong Kong. We
      report a 55-year-old bedridden man with S. suis meningitis complicated with
      ventriculoperitoneal shunt infection and lumbar spine spondylodiscitis. He
      presented with fever, delirium, neck stiffness, lower leg weakness and sudden
      onset hearing loss for several days. He was successfully treated with intravenous
      antibiotics, ventriculoperitoneal shunt replacement, lumbar spinal laminotomy and
      discectomy. Cerebrospinal fluid culture initially misidentified the organism as
      Streptococcus acidominimus, and S. suis was later identified by 16S rRNA
      sequencing. Misidentification of the microbiological findings may lead to a
      failure to correctly diagnose this disease. S. suis meningitis should be included
      in the differential diagnosis of patients with meningitis and sudden hearing
      loss.

PMID- 16607455
TI  - Proximal common pathway in the circuit of atrioventricular nodal reentrant
      tachycardia.
AB  - Whether atrium tissue is involved in the reentrant circuit of atrioventricular
      nodal reentrant tachycardia (AVNRT) has been debated for decades. Animal models,
      clinical electrophysiological studies, surgery and catheter ablation have all
      documented that the perinodal tissue forms part of the tachycardia circuit.
      However, the occasional clinical finding of AVNRT with ventriculoatrial block
      suggests the presence of a proximal common pathway. We describe a 43-year-old
      woman who developed recurrent AVNRT with new onset of complete ventriculoatrial
      block after an attempted radiofrequency ablation at the posterior septal area.
      This case demonstrates the anatomical existence of a proximal common pathway and
      the topological location of such a pathway for typical AVNRT. This case also
      demonstrates the isolated nature of the AVNRT circuit and the delicate nature of
      the responsible reentrant substrate.

PMID- 16607456
TI  - Rapidly fatal Langerhans' cell histiocytosis in an adult.
AB  - Langerhans' cell histiocytosis (LCH) is a disorder of unknown etiology,
      characterized by abnormal proliferation of cells of the dendritic cell lineage.
      The acute disseminated form of the disease characteristically occurs in children
      younger than 3 years of age. More indolent forms of LCH occur primarily in older
      children and young adults. The prognosis for patients with LCH is good. We report
      a 28-year-old man with acute disseminated LCH who initially presented with fever,
      chills, and dry cough. Diagnosis of LCH was confirmed by bronchoalveolar lavage
      fluid cytology, and skin and bone marrow biopsies. Conventional chemotherapy was
      not given, because of the patient's poor clinical condition, including
      respiratory failure, unstable vital signs, and impaired consciousness. Salvage
      thalidomide therapy was started on the 12th day of hospitalization. The patient
      died from multisystem LCH with septic shock and multiple organ failure on the
      22nd day of hospitalization. This report illustrates the diagnostic features and
      treatment of LCH in a rapidly fatal case of adult LCH.

PMID- 16607457
TI  - Potassium-titanyl-phosphate laser nasopharyngectomy with nasopharyngoscopic
      guidance for recurrent nasopharyngeal carcinoma.
AB  - Management of recurrent nasopharyngeal carcinoma is a challenge to head and neck
      surgeons. Traditional methods of nasopharyngectomy for the treatment of recurrent
      nasopharyngeal carcinoma carry considerable complications. This report describes
      the technique of potassium-titanyl-phosphate (KTP) laser nasopharyngectomy under
      nasopharyngoscopic guidance. This technique allows access to the nasopharynx
      without damaging structures in the facial region. It results in minimal blood
      loss, and requires no nasal packing. We report the use of this technique to treat
      6 patients with recurrent nasopharyngeal carcinoma. All patients were able to
      resume their oral diet 8 hours after recovery from general anesthesia, and were
      discharged within 2 days. Our results suggest that this technique is useful for
      excising locally recurring nasopharyngeal carcinomas. Prospective trial of this
      technique with long-term follow-up is necessary to determine its effectiveness
      and safety.

PMID- 16607458
TI  - Intrafamilial phenotype variation in Marfan syndrome ascertained by intragenic
      linkage analysis.
AB  - Marfan syndrome is an autosomal dominant fibrillinopathy caused by mutations of
      the fibrillin-1 (FBN1) gene. Although linkage analysis is often required to
      ascertain the disease status in family members, recombination is a problem. We
      analyzed 6 families including 18 patients using 4 intragenic microsatellite
      markers, located in intron 1, 5, 28, and 43, respectively, of the FBN1 gene.
      Haplotypes in all family members could be established, and segregation analysis
      showed no recombination between the markers and the disease. After confirming the
      diagnosis, intrafamilial analysis revealed clinical manifestations involving the
      ocular, cardiac, and skeletal systems. Intragenic linkage analysis in Marfan
      syndrome is very helpful in its diagnosis and management within affected
      families.

PMID- 16607459
TI  - Risk of microbial contamination of unit-dose eyedrops within twenty four hours
      after first opening.
AB  - The purpose of this study was to evaluate the risk of microbial contamination of
      sterile, preservative-free, unit-dose ocular medications within 24 h after the
      first opening. Four different unit-dose ocular medications (cromolyn sodium,
      timolol, gentamicin sulfate, and betamethasone) in 1 mL containers, were tested.
      After opening, the preparations were stored in an acrylic protector with or
      without cap, at room temperature or in a refrigerator at 4 degrees C. Samples
      were collected for microbiological cultures at 0, 4, 10, 14, and 24 h after
      opening from the identical container. No bacteria or fungus was detected in the
      samples throughout the period of the study. Microbial air contamination of the
      experimental environment was also studied. The culture results of environmental
      microbial air contamination were positive for both bacteria and fungi. This study
      suggests that unit-dose eyedrops remain free of microbial air contamination for
      up to 24 h after the first opening.

PMID- 16607460
TI  - No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2
      diabetes in a Japanese population.
AB  - Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1)
      inhibits insulin signal transduction pathway(s). Previous studies have
      demonstrated the K121Q variant of the ENPP1 gene to have a significant functional
      role in determining susceptibility to insulin resistance and type 2 diabetes
      (T2D). To assess whether the K121Q variant has any impact on T2D in Japanese, we
      undertook an extensive case-control association study using a total of 911
      unrelated Japanese T2D patients and 876 control subjects. No significant
      difference was observed in either genotype distribution (P=0.95) or allele
      frequency (P=0.83) between T2D and control groups. Notably, the frequency of the
      ancestral Q121 allele, which is also present in other primates, was quite high in
      African-Americans, and showed a marked ethnic variation (77.3% in African
      Americans, 16.7% in European Americans, 10.5% in Japanese and 4.2% in Han
      Chinese). Consequently, the pairwise F(ST )value (a classic measure of genetic
      distance between pairs of population) showed highly significant differentiations
      between African-American and non-African-American populations (F(ST)>0.3). Our
      results indicated that the K121Q variant of the ENPP1 gene has very little, if
      any, impact on T2D susceptibility in Japanese, but may play a role in the inter
      ethnic variability in insulin resistance and T2D.

PMID- 16607461
TI  - Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe
      disease, and new genotype-phenotype correlation.
AB  - Krabbe disease is an autosomal recessive leukodystrophy. It is pathologically
      characterized by demyelination of the central and peripheral nervous systems and
      the accumulation of globoid cells in brain white matter. It is caused by a
      deficiency of galactocerebrosidase (GALC) activity. We investigated mutations of
      the GALC gene in 17 Japanese patients with Krabbe disease, the largest subject
      number of Japanese patients to date, and found 27 mutations. Of these mutations,
      six were novel, including two nonsense mutations, W115X and R204X, two missense
      mutations, S257F and L364R, a small deletion, 393delT, and a small insertion,
      1719-1720insT. Our findings, taken with the reported mutations in Japanese
      patients, confirm several mutations common to Japanese patients, the two most
      frequent being 12Del3Ins and I66M+I289V, which account for 37% of all mutant
      alleles. With two additional mutations, G270D and T652P, these account for up to
      57% of genetic mutations in Japanese patients. Distribution of the mutations
      within the GALC gene indicated some genotype-phenotype correlation. I66M+I289M,
      G270D, and L618S contributed to a mild phenotype. Screening for these mutations
      may provide an effective method with which to predict the clinical phenotype.

PMID- 16607464
TI  - Morphometric side-to-side differences in human cruciate ligament insertions.
AB  - Graft placement in cruciate ligament reconstruction is known to significantly
      influence postoperative knee stability and range of motion. Improvement of bone
      tunnel positioning has been advocated by computer-assisted surgical procedures
      that require reliable input and reference data. This study validates the
      hypothesis that morphometric reference data can be obtained from the uninjured
      controlateral knee for accurate bone tunnel and graft positioning. Thirty pairs
      of human cadaver knees were dissected and the femoral and tibial footprints of
      the anterior and posterior cruciate ligaments (PCL) were radiopaquely marked.
      Radiographs were taken of the corresponding left- and right-sided femora and
      tibiae, and digitally processed. Controlateral specimens were mirrored and
      overlapped precisely, the areas and intersections of ligament insertion were
      digitally determined. There were no significant differences in the total area of
      cruciate ligament insertion between left and right knee specimens or between
      female and male specimens. Intersection areas (IAs) in femoral and tibial
      anterior cruciate ligament (ACL) insertions averaged 31.3 and 33.4% of the total
      insertion area, respectively. The center of gravity for the femoral and tibial
      ACL footprint differed by 4.7 and 4.5 mm between left and right knees,
      respectively. IAs in femoral and tibial PCL insertions averaged 46.1 and 61.3% of
      the total insertion area, respectively. The center of gravity for the femoral and
      tibial PCL footprint differed by 4.5 and 2.4 mm between left and right knees,
      respectively. Our study does not support the concept of obtaining morphologic
      reference data from the uninjured controlateral knee for individual bone tunnel
      placement.

PMID- 16607462
TI  - Evolutionary dynamics of olfactory and other chemosensory receptor genes in
      vertebrates.
AB  - The numbers of functional olfactory receptor (OR) genes in humans and mice are
      about 400 and 1,000 respectively. In both humans and mice, these genes exist as
      genomic clusters and are scattered over almost all chromosomes. The difference in
      the number of genes between the two species is apparently caused by massive
      inactivation of OR genes in the human lineage and a substantial increase of OR
      genes in the mouse lineage after the human-mouse divergence. Compared with
      mammals, fishes have a much smaller number of OR genes. However, the OR gene
      family in fishes is much more divergent than that in mammals. Fishes have many
      different groups of genes that are absent in mammals, suggesting that the
      mammalian OR gene family is characterized by the loss of many group genes that
      existed in the ancestor of vertebrates and the subsequent expansion of specific
      groups of genes. Therefore, this gene family apparently changed dynamically
      depending on the evolutionary lineage and evolved under the birth-and-death model
      of evolution. Study of the evolutionary changes of two gene families for
      vomeronasal receptors and two gene families for taste receptors, which are
      structurally similar, but remotely related to OR genes, showed that some of the
      gene families evolved in the same fashion as the OR gene family. It appears that
      the number and types of genes in chemosensory receptor gene families have evolved
      in response to environmental needs, but they are also affected by fortuitous
      factors.

PMID- 16607465
TI  - New findings on intermetacarpal fat pads: anatomy and imaging.
AB  - Many studies have focused on the functional importance of the gliding structures
      of the hand. These structures are clinically important in reconstructive surgery
      and mechanically essential for an efficient hand grasp. The aims of this study
      were to first review the intermetacarpal space and then focus on its fatty
      tissue, the intermetacarpal fat pad. This study used dissections and histological
      analysis of fetal and adult hands and CT scans of adult hands. The
      intermetacarpal fat pads are well-defined adipose structures located between the
      heads of the second, third, fourth and fifth metacarpal bones. They are located
      in spaces defined by the palmar fascia and its deep expansions. These spaces are
      closed distally but open proximally into the tunnels surrounding the flexor
      tendons (Legueu and Juvara canals). The pads are composed of non-mobilizable fat;
      they protect the neurovascular pedicles of the fingers. They may act with the
      palmar skin to mitigate compressive and shear forces during gripping. Finally
      they may be involved in neurological symptoms if their size is increased by any
      trauma or inflammatory process.

PMID- 16607466
TI  - NMR assignment of M-crystallin: a novel Ca2+ binding protein of the betagamma
      crystallin superfamily from Methanosarcina acetivorans.

PMID- 16607467
TI  - NMR assignment of the spinophilin PDZ domain (493-602).

PMID- 16607468
TI  - Pramipexole versus sertraline in the treatment of depression in Parkinson's
      disease: a national multicenter parallel-group randomized study.
AB  - In addition to treating the motor symptoms of Parkinson's disease, the dopamine
      agonist pramipexole has shown an antidepressant effect. The trials, however,
      included patients with motor complications, raising the question of whether the
      antidepressant benefit represented only a treatment-related motor improvement. To
      address this issue, we have conducted a 14-week randomized trial comparing
      pramipexole with an established antidepressant in patients without motor
      complications. At seven Italian centers, 67 Parkinsonian outpatients with major
      depression but no history of motor fluctuations and/or dyskinesia received open
      label pramipexole (at 1.5 to 4.5 mg/day) or sertraline (at 50 mg/day). In both
      groups, the Hamilton Depression Rating Scale (HAM-D) score decreased throughout
      12 weeks of treatment, but in the pramipexole group the proportion of patients
      who recovered, as defined by a final HAM-D score </= 8,was significantly higher,
      at 60.6% versus 27.3% (p = 0.006). Patients' self-ratings improved in both
      groups. All adverse events were mild or moderate, but five patients (14.7%)
      withdrew from the sertraline group. Despite the absence of motor complications,
      the pramipexole recipients showed improvement on the Unified Parkinson's Disease
      Rating Scale (UPDRS) motor subscore. We conclude that dopamine agonists may be an
      alternative to antidepressants in Parkinson's disease.

PMID- 16607470
TI  - Musical hallucinations in a musician.
AB  - The experience of music is difficult to study objectively. Here we describe a
      detailed analysis of musical hallucinations developing after a probable brainstem
      stroke in an 83 year old musician who was able to describe and notate the
      hallucinations. The hallucinations comprised simple, repetitive melodic and
      rhythmic motifs that were combined apparently randomly without definite tonality,
      large-scale structure, or timbre. This observation is consistent with the
      proposal that musical hallucinations represent abnormal spontaneous activity in
      auditory cortical areas beyond the primary auditory cortex. This activity may
      generate novel musical motifs.

PMID- 16607469
TI  - Does subthalamic nucleus stimulation induce apathy in Parkinson's disease?
AB  - BACKGROUND: Subthalamic Nucleus Deep Brain Stimulation (STN-DBS) has been shown
      to significantly improve motor symptoms in advanced Parkinson's disease (PD).
      Only few studies, however, have focused on the non-motor effects of DBS. METHODS:
      A consecutive series of 15 patients was assessed three months before (M-3), then
      three months (M3) and six months (M6) after surgery. Mean (+/- SD) age at surgery
      was 59.7 (7.6). Mean disease duration at surgery was 12.2 (2.8) years. The Mini
      International Neuropsychiatric Inventory was used to assess psychiatric disorders
      three months before surgery. Depression was evaluated using Montgomery and Asberg
      Rating Scale (MADRS). Anxiety was evaluated using the AMDP system (Association
      for Methodology and Documentation in Psychiatry). Apathy was particularly
      evaluated using the Apathy Evaluation Scale (AES) and the Starkstein Scale. All
      these scales were performed at every evaluation. RESULTS: Apathy worsened at M3
      and M6 after STN-DBS in comparison with the preoperative evaluation: the AES mean
      score was significantly impaired between the preoperative (38.4+/-7.1) and both
      the postoperative M3 (44.6+/-9.5, p = 0.003) and M6 scores (46.0+/-10.9, p =
      0.013). Significant worsening of apathy was confirmed using the Starkstein scale.
      There was no evidence of depression: the mean MADRS score did not differ before
      surgery (9.1+/-7.4) and at both M3 (8.6+/-8.2) and M6 (9.9+/-7.7) after STN-DBS.
      The anxiety level did not change between preoperative (9.4+/-9.2) and both M3
      (5.5+/-4.5) and M6 (6.6+/-4.6) postoperative states. CONCLUSION: Although STN-DBS
      constitutes a therapeutic advance for severely disabled patients with Parkinson's
      disease, we should keep in mind that this surgical procedure may contribute to
      the inducing of apathy. Our observation raises the issue of the direct influence
      of STN- DBS on the limbic system by diffusion of stimulus to the medial limbic
      compartment of STN.

PMID- 16607471
TI  - Lesion probability maps of white matter hyperintensities in elderly individuals:
      results of the Austrian stroke prevention study.
AB  - OBJECTIVE: White matter hyperintensities (WMH) are common on brain MRI of the
      elderly. Their size ranges from punctate to early confluent to confluent lesions.
      While this increase in extension is frequently seen as evidence for a continuum
      of changes, histological data and clinical follow-up suggest differences in
      underlying pathology and their progression. METHODS: We tested this hypothesis by
      exploring the distributions of punctuate and confluent lesions using lesion
      probability maps (LPM) generated from MRI scans of 189 participants (mean age
      60.8+/-6.2 years) in the Austrian Stroke Prevention Study. We dichotomised WMH
      according to the classification by Fazekas et al. [punctate (n=143) vs. early
      confluent and confluent (n=33)] to run voxel-based t-tests using permutation
      based nonparametric inference. To test alternative hypotheses, we created similar
      LPM for age and arterial hypertension. RESULTS: We observed significant
      differences in the spatial distribution of lesions for the two WMH groups
      (p<0.01). Punctate lesions were more diffusely distributed throughout the
      cerebral white matter (peak probability approximately 5%) relative to confluent
      lesions (peak probability 45%). Confluent lesions had greatest likelihood of
      being found in perfusion "watershed" regions. These differences in distribution
      could not be explained by differences in age or hypertension only, as both
      greater age and the diagnosis of hypertension were associated with WMH abutting
      the occipital horns. CONCLUSIONS: Punctate and early confluent to confluent WMH
      show distinguishable differences in their spatial distribution within a normal
      elderly population. The pattern of punctate WMH is probably a consequence of
      mixed etiologies. Preferential localization of the more confluent WMH with
      arterial watershed areas implies a stronger ischemic component in their
      development.

PMID- 16607472
TI  - Central motor drive and perception of effort during fatigue in multiple
      sclerosis.
AB  - OBJECTIVE: To determine if task performance and fatiguability during repeated low
      level contractions of an intrinsic hand muscle differ in a group of MS subjects
      compared with a control group, and what central changes accompany the development
      of fatigue and the period of recovery, whether these measures are related to
      subjective ratings of fatigue or perception of effort. METHODS: Force of index
      finger abduction, rating of perceived effort, and motor evoked potential
      amplitude and silent period duration were measured during and after a 20-min.
      intermittent submaximal (40%) contraction of the first dorsal interosseous muscle
      in 23 clinically definite MS subjects with mild-moderate symptoms, and 15
      controls. RESULTS: Rating of perceived effort increased at a greater rate in the
      MS group than in control subjects during exercise, and this was associated with
      larger increases in both MEP amplitude and silent period duration. CONCLUSIONS:
      Submaximal fatiguing exercise is associated with an enhanced central motor drive
      and increased perception of effort in MS. SIGNIFICANCE: MS subjects can increase
      central drive during fatiguing exercise to a greater degree than controls, but
      this is associated with greater perceived exertion. These factors may underlie
      the more general complaint of fatigue experienced by people with MS.

PMID- 16607473
TI  - Profound midbrain atrophy in patients with Wilson's disease and neurological
      symptoms?
AB  - Wilson's disease (WD) is characterized by impaired hepatic copper secretion and
      subsequent copper accumulation in many organs predominantly liver and brain,
      secondary to loss of function mutations in the copper transport protein ATP7B. If
      the disease is recognized too late or treatment is not adequate, brain copper
      accumulation leads to progressive neurodegeneration with a variety of clinical
      symptoms. The nigrostriatal dopaminergic system seems rather vulnerable. Midbrain
      atrophy, however, has not been recognized as one of the prime features of
      patients with WD. Here we report quantification of midbrain diameter in 41
      patients with WD. Data were correlated to the severity of neurological symptoms
      and the integrity of dopaminergic neurons measured via dopamine transporter
      binding. For control, we measured midbrain diameter in 18 patients with no
      evidence for brainstem dysfunction and 5 patients with progressive supranuclear
      palsy (PSP). Patients with WD had a reduced midbrain diameter (15.5 +/- 0.4 mm)
      compared to controls (18.5 +/- 0.2 mm). WD patients without neurological symptoms
      had midbrain diameter that were not different from controls (18.0 +/- 0.3 mm),
      while patients with neurological symptoms showed midbrain atrophy similar to
      patients with PSP (14.4 +/- 0.3 mm versus 14.1 +/- 0.3). There was a strong and
      significant correlation between midbrain atrophy and the severity of neurological
      symptoms (r= -0.68, p < 0.001) while midbrain atrophy and dopamine transporter
      binding correlated significantly but was less pronounced (r=0.46, p < 0.001). In
      summary, we were able to show, that midbrain diameter is an easy to perform
      quantification of neurodegeneration induced by brain copper accumulation and that
      other structures than substantia nigra dopaminergic neurons seem to contribute to
      midbrain atrophy in WD.

PMID- 16607474
TI  - GDAP1 mutation in autosomal recessive Charcot-Marie-Tooth with pyramidal
      features.

PMID- 16607475
TI  - Three patients with migraine following caloric-induced vestibular stimulation.
AB  - The co-occurrence of migraine and dizziness is greater than would be expected by
      chance. We report 3 patients who developed migraine following acute vertigo
      precipitated during caloric testing. A small proportion of the epidemiological
      links between migraine and vertigo may be due to vertigo-triggered migraine.

PMID- 16607476
TI  - Dynamics of viscous vesicles in shear flow.
AB  - The dynamics of giant lipid vesicles under shear flow is experimentally
      investigated. Consistent with previous theoretical and numerical studies, two
      flow regimes are identified depending on the viscosity ratio between the interior
      and the exterior of the vesicle, and its reduced volume or excess surface. At low
      viscosity ratios, a tank-treading motion of the membrane takes place, the vesicle
      assuming a constant orientation with respect to the flow direction. At higher
      viscosity ratios, a tumbling motion is observed in which the whole vesicle
      rotates with a periodically modulated velocity. When the shear rate increases,
      this tumbling motion becomes increasingly sensitive to vesicle deformation due to
      the elongational component of the flow and significant deviations from simpler
      models are observed. A good characterization of these various flow regimes is
      essential for the validation of analytical and numerical models, and to relate
      microscopic dynamics to macroscopic rheology of suspensions of deformable
      particles, such as blood.

PMID- 16607478
TI  - DNA damage induced nucleotide excision repair in Saccharomyces cerevisiae.
AB  - Nucleotide excision repair (NER) is the most versatile and universal pathway of
      DNA repair that is capable of repairing virtually any damages other than a double
      strand break (DSB). This pathway has been shown to be inducible in several
      systems. However, question of a threshold and the nature of the damage that can
      signal induction of this pathway remain poorly understood. In this study it has
      been shown that prior exposure to very low doses of osmium tetroxide enhanced the
      survival of wild type Saccharomyces cerevisiae when the cells were challenged
      with UV light. Moreover, it was also found that osmium tetroxide treated rad3
      mutants did not show enhanced survival indicating an involvement of nucleotide
      excision repair in the enhanced survival. To probe this further the actual
      removal of pyrimidine dimers by the treated and control cells was studied. Osmium
      tetroxide treated cells removed pyrimidine dimers more efficiently as compared to
      control cells. This was confirmed by measuring the in vitro repair synthesis in
      cell free extracts prepared from control and primed cells. It was found that the
      uptake of active (32)P was significantly higher in the plasmid substrates
      incubated with extracts of primed cells. This induction is dependent on de novo
      synthesis of proteins as cycloheximide treatment abrogated this response. The
      nature of induced repair was found to be essentially error free. Study
      conclusively shows that NER is an inducible pathway in Saccharomyces cerevisiae
      and its induction is dependent on exposure to a threshold of a genotoxic stress.

PMID- 16607479
TI  - Adherence to generic reverse transcriptase inhibitor-based antiretroviral
      medication at a Tertiary Center in North India.
AB  - At least 95% adherence to medications is required for sustained response to
      antiretroviral therapy (ART). In resource constraint restrained settings it is
      not possible to use electronic methods to determine adherence. We determined
      adherence during the previous 4 weeks by the recall method in 200 patients (138
      males) receiving generic triple drug reverse transcriptase inhibitor-based
      antiretroviral medications. They were administered a uniform questionnaire to
      determine the number of time they forgot or were unable to take their medications
      and the reasons thereof. One hundred and fifty received two and 50 took three
      pills daily. One hundred and forty-seven did not miss any dose. Fifty-three
      (26.5%) missed at least one dose during the preceding 4 weeks. Thirty-one took
      treatment on and off. Seven missed a dose in the preceding 3 days, nine more
      between the last 3 and 7 days, and six from 1 to 4 weeks. The major reasons for
      non-adherence were financial constraints, forgetting to take the medication, drug
      toxicity, lack of access to the drug, fear of getting immune to the benefit of
      the drug, and to avoid adverse effects. Non-adherence in 26.5% individuals could
      be an additional factor that can increase the risk of drug resistance.

PMID- 16607481
TI  - Pregnancy-induced vesical decidualized endometriosis simulating a bladder tumor.
AB  - Vesical endometriosis accounts for approximately 1% of all discovered cases of
      endometriosis. We report the first case of a 36-year-old woman with pregnancy
      associated decidual changes within bladder endometriosis that are clinically
      presented as a rapidly growing bladder tumor. Cystoscopy, with subsequent cold
      cup biopsy and fulguration, revealed a solitary, red-brown, nodular lesion, which
      turned to be a decidualized endometriosis of the urinary bladder. Delivery and
      postdelivery follow-up was uneventful and no recurrence was diagnosed.

PMID- 16607482
TI  - Spontaneous extrusion of sacral nerve implant secondary to massive weight loss.
AB  - Sacral neuromodulation (Interstim, Medtronic, Minneapolis, Minnesota) is a
      recognized treatment for refractory urgency, frequency, and urge incontinence.
      Revision rates range from 10-33% mainly for pain over the implantable pulse
      generator site (IPG) or lead migration [Hassouna et al. J Urol 163:1849-1854,
      2000; Schmidt et al. J Urol 162:352-357, 1999; Spinelli et al. J Urol 166:541
      545, 2001; Swinn et al. Eur Urol 38:439-443, 2000; Weil et al. Eur Urol 37:161
      171, 2000; Evaraert et al. Int Urogynecol J Pelvic Floor Dysfunct 11:231-236,
      2000]. We report a case of spontaneous extrusion of the IPG through the
      subcutaneous fat and skin secondary to marked weight loss after gastric bypass
      surgery. Continued weight loss resulted in multiple surgical interventions and
      eventual removal of the device.

PMID- 16607483
TI  - [Therapeutic goals and outcome measurements in COPD patients].
AB  - Due to the complex pathogenesis of chronic obstructive pulmonary disease (COPD)
      with systemic effects and different subjective perceptions, responses to therapy
      are difficult to assess. Though lung function tests correlate poorly with
      important features of the disease such as survival and quality of life,
      spirometric measures, especially forced expiratory volume (FEV(1)) and
      inspiratory capacity, the 6-min walk test, exacerbation indices, dyspnea scales
      and health status measurements remain important outcomes in clinical studies as
      well as in clinical practice. Markers of airway inflammation are receiving
      increased attention. The BODE index, combining functional and systemic outcomes,
      is a better predictor of mortality than FEV(1) and, therefore, particularly
      valuable.

PMID- 16607477
TI  - New concepts in surgery of WHO grade II gliomas: functional brain mapping,
      connectionism and plasticity--a review.
AB  - Despite a recent literature supporting the impact of surgery on the natural
      history of low-grade glioma (LGG), the indications of resection still remain a
      matter of debate, especially because of the frequent location of these tumors
      within eloquent brain areas - thus with a risk to induce a permanent
      postoperative deficit. Therefore, since the antagonist nature of this surgery is
      to perform the most extensive glioma removal possible, while preserving the
      function and the quality of life, new concepts were recently applied to LGG
      resection in order to optimize the benefit/risk ratio of the surgery.First, due
      to the development of functional mapping methods, namely perioperative
      neurofunctional imaging and intrasurgical direct electrical stimulation, the
      study of cortical functional organization is currently possible for each patient 
      in addition to an extensive neuropsychological assessment. Such knowledge is
      essential because of the inter-individual anatomo-functional variability,
      increased in tumors due to cerebral plasticity phenomena. Thus, brain mapping
      enables to envision and perform a resection according to individual functional
      boundaries.Second, since LGG invades not only cortical but also subcortical
      structures, and shows an infiltrative progression along the white matter tracts,
      new techniques of anatomical tracking and functional mapping of the subcortical
      white matter pathways were also used with the goal to study the individual
      effective connectivity - which needs imperatively to be preserved during the
      resection.Third, the better understanding of brain plasticity mechanisms, induced
      both by the slow-growing LGG and by the surgery itself, were equally studied in
      each patient and applied to the surgical strategy by incorporating individual
      dynamic potential of reorganization into the operative planning. The integration
      of these new concepts of individual functional mapping, connectivity and plastic
      potential to the surgery of LGG has allowed an extent of surgical indications, an
      optimization of the quality of resection (neuro-oncological benefit), and a
      minimization of the risk of sequelae (benefit on the quality of life). In
      addition, such a strategy has also fundamental applications, since it represents
      a new door to the connectionism and cerebral plasticity.

PMID- 16607484
TI  - [Pharmacological treatment of COPD and future of anti-inflammatory therapy].
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by airflow
      limitation that is not fully reversible. It is caused by chronic inflammation of
      the airways and the lung parenchyma. Symptomatic treatment is based on
      bronchodilatation, which leads to a reduction of hyperinflation and relief of
      dyspnea. Smoking cessation is the only known causative treatment option. Inhaled
      corticosteroids (ICS) reduce exacerbations and, potentially, mortality. Future
      therapies should ameliorate chronic inflammation and thus stop the annual decline
      of lung function. In face of increasing mortality and morbidity more research is
      needed.

PMID- 16607485
TI  - [COPD-nonpharmacological treatment].
AB  - The modern concept of chronic obstructive pulmonary disease (COPD) goes far
      beyond pure medical therapy. Solely treating obstruction and inflammation of the
      airways does not correspond to the complexity of this illness which now is
      considered a systemic disease. Therapeutic planning comprises prevention, early
      physiotherapy and physical training, educational measures, and, in advanced
      stages, long-term oxygen therapy, mechanical support of the ventilatory muscular
      system by noninvasive ventilation and surgical measures. To stop smoking is the
      most important preventive measure which succeeds in up to 40% when carried
      through consequently. COPD will eventually lead to a steadily decreasing
      cardiopulmonary performance. Physical training therefore is of utmost importance.
      Physical training will be accompanied by ventilatory and physiotherapy, a
      sophisticated dietary treatment, as well as education and motivation of the
      patient in order to develop competence in self-management. Further treatments in
      advanced stages consist of long-term oxygen therapy and intermittent noninvasive
      ventilation. The latter is the treatment of choice for acute respiratory
      insufficiency. Operative treatments like lung volume reduction and lung
      transplantation are only indicated in selected cases.

PMID- 16607486
TI  - [Therapy-resistant asthma--a distinct phenotype?].
AB  - While most patients respond well to conventional antiasthmatic therapy as
      outlined in current guidelines, a small percentage, however, have severe disease
      which is relatively or completely unresponsive to inhaled as well as oral
      medications. These patients who often have a long-standing "career" in asthma are
      frequently labeled steroid-resistant or difficult-to-control but this group of
      patients is not well defined. It is likely that a number of mechanisms contribute
      to therapy-resistant asthma such as socioeconomic status, mental disturbances but
      also characteristics of the individual subgroups within the syndrome of asthma
      such as aspirin-exacerbated airway disease or intrinsic asthma. A thorough and
      systematic approach is required in the work-up of these patients which sometimes
      involves repeated evaluations to determine that asthma and not other diseases
      such as chronic obstructive pulmonary disease (COPD), emphysema, gastroesophageal
      reflux, congestive heart failure and many others which can mimic asthma are
      present. Issues relating to compliance with prior or future therapies are
      warranted and doctor-patient communication should be checked. A meticulous search
      for possible triggers such as cigarette smoking, occupational allergens and
      comorbid conditions should be included in the work-up. High-dose combination
      therapy including frequent bursts or maintenance therapy with systemic
      corticosteroids is often necessary. Alternative therapies such as methotrexate
      and other immunosuppressants should be avoided based on current data but recent
      evidence from controlled studies suggests that anti-IgE or anti-tumor necrosis
      factor-(TNF-)alpha strategies might be of benefit in these patients. There is
      data that different phenotypes of therapy-resistant asthma might exist but little
      if any evidence to suggest a single phenotype of therapy-resistant asthma.

PMID- 16607487
TI  - [Pulmonary fibrosis--a therapeutic dilemma?].
AB  - The idiopathic interstitial pneumonias, especially the idiopathic pulmonary
      fibrosis (IPF), are life-threatening lung disorders, for which no effective
      treatment option exists. In view of IPF, the American Thoracic Society
      (ATS)/European Respiratory Society (ERS) consensus statement recommends a
      combined therapy with corticosteroids and azathioprine or cyclophosphamide,
      although data from conclusive clinical trials are yet missing and the recurrent
      clinical experience is that these drugs do not really help in IPF. Up to now,
      lung transplantation represents the last and only therapeutic option for IPF
      subjects. Based on new pathophysiological concepts of IPF, there are meanwhile a
      couple of different agents under preclinical and clinical assessment, and the
      increasing number of clinical trials ongoing in IPF raise the hope that an
      effective treatment comes into reach. The agents investigated and their targets
      are: acetylcysteine (reactive oxygen species [ROS] scavenging), interferon-gamma
      1b (modulation of Th1/Th2 balance, direct antifibrotic effects), pirfenidone and
      GC 1008 (blockade of transforming growth factor-beta), FG 3019 (blockade of
      connective tissue growth factor), imatinib mesylate (blockade of platelet-derived
      growth factor), bosentan (blockade of endothelin), zileutin (blockade of
      leukotrienes), etanercept (blockade of tumor necrosis factor-alpha), heparin
      (alveolar anticoagulation). Hopefully, these new therapeutic strategies may help
      to improve prognosis of IPF in the future.

PMID- 16607488
TI  - [What is new in the treatment of community-acquired pneumonia?].
AB  - Community-acquired pneumonia (CAP) is the most important infectious disease in
      Germany. After 3 years of data recording, the country-wide competence network
      CAPNETZ presents reliable data on etiology and course of the disease, based on
      more than 3,500 prospectively observed patients. In the acute phase, lethality is
      as high as nearly 10%, and in the 6-month follow-up period after the acute
      infection, lethality is > 15%. A reliable detection of the underlying pathogen is
      possible in less than half of all patients studied. The most frequent pathogens
      are Streptococcus pneumoniae (40%), Haemophilus influenzae, and Mycoplasma
      pneumoniae (8% each). Legionella (3%) and Chlamydia pneumoniae (< 1%) are rarely
      found, and gram-negative enterobacteriaceae (< 5%) are restricted to high-risk
      patient groups (nursing home, multimorbidity). CAPs due to pneumococci,
      legionella or enterobacteriaceae were associated with increased lethality.
      Problems with resistances had not been found in Germany, except for a decreasing
      susceptibility of S. pneumoniae to macrolides. Viruses could be detected in
      nearly 15% of all pneumonia patients. The CRB-65 score allows a reliable
      discrimination between patients with a high and low risk of dying. The new S3
      guideline for diagnosis and treatment of CAP recommends a risk-adapted treatment.
      Low-risk patients shall receive a monotherapy with, e. g., amoxicillin, high-risk
      patients should be treated with a broad-spectrum combination therapy (beta-lactam
      and macrolide).

PMID- 16607489
TI  - [Obstructive sleep apnea-related cardiovascular disease].
AB  - The clinical spectrum of obstructive sleep apnea-(OSA-)related cardiovascular
      disease (CVD) comprises systemic arterial hypertension (prevalence: 40-60%),
      pulmonary hypertension (20-30%), coronary artery disease (20-30%), congestive
      heart failure (5-10%), and stroke (5-10%). During sleep, heart rhythm disorders
      such as atrioventricular blocks, sinus arrests and atrial fibrillation can be
      induced by OSA. OSA-related CVD mainly affects those patients with an apnea
      hypopnea index > 30/h and, if left untreated, is linked to increased mortality.
      Epidemiologic data have clearly shown that cardiovascular risk is increased in
      OSA independent of confounding factors such as obesity and concomitant metabolic
      disease. In recent years, the pathophysiology of OSA-related CVD has been further
      elucidated showing that apart from the well-known sympathetic activation,
      increased oxidative stress and pro-inflammatory changes seem to play major roles.
      Furthermore, studies using high resolution ultrasonography have demonstrated
      endothelial dysfunction and enhanced atherosclerosis in these patients. Finally,
      animal models of OSA have delineated that daytime arterial hypertension is the
      consequence of the OSA-associated chronic intermittent hypoxia. Therapy of OSA by
      continuous positive airway pressure (CPAP) ventilation exerts cardioprotective
      effects. It has been shown to rectify the vascular micromilieu, restore
      endothelium-dependent vasodilation, lower 24-h blood pressure, eliminate
      nocturnal heart rhythm disorders, and improve left ventricular function.
      Furthermore, long-term CPAP therapy leads to a reduction in important clinical
      endpoints such as the rates of myocardial infarction and stroke.

PMID- 16607491
TI  - [Intermediate care units and noninvasive ventilation].
AB  - Intermediate care units (IMC) have been introduced to provide optimal patient
      management according to disease severity and to bridge the gap between intensive
      care (ICU) and general wards. Most patients that are referred to an IMC need
      monitoring and intensive analgetic treatment. Over the past years noninvasive
      ventilation (NIV) and weaning have emerged as important new forms of active
      treatment in the IMC. Most studies that have been published so far demonstrate
      that an IMC improves patient outcome and lowers costs, although randomized
      controlled trials are missing. NIV reduces mortality, the need for intubation as
      well as ICU and hospital length of stay in patients with chronic obstructive
      pulmonary disease (COPD) and other disorders that cause respiratory failure. In
      many cases NIV can be performed in the IMC, a fact that reduces the number of ICU
      admissions, lowers costs and improves patient care. The high prevalence of
      pulmonary diseases and NIV emphasizes the importance of pneumologists as
      directors of both ICU and IMC.

PMID- 16607490
TI  - [Pulmonary hypertension: the future has begun].
AB  - In recent years, pulmonary hypertension got into the focus of research due to the
      development of efficacious medications and the discovery of important pathologic
      mechanisms of disease. Currently, prostanoids, endothelin receptor antagonists
      and phosphodiesterase 5 inhibitors are the most important substance groups used
      for treatment. Substances that are emerging in tumor therapy (tyrosine kinase
      inhibitors, epidermal growth factor [EGF] und platelet-derived growth factor
      [PDGF] receptor blockers), vasoactive intestinal peptide (VIP), rho-kinase
      inhibitors and targeted drugs for endothelial dysfunction will be evaluated as
      future drugs for pulmonary hypertension. Improving early diagnosis of pulmonary
      hypertension will be an important task in the future. Both the development of
      diagnostic methods with increased sensitivity and specificity and a broad
      awareness program will be necessary to achieve this goal.

PMID- 16607492
TI  - Life in the sabkha: Raman spectroscopy of halotrophic extremophiles of relevance
      to planetary exploration.
AB  - The Raman spectroscopic biosignatures of halotrophic cyanobacterial extremophiles
      from sabkha evaporitic saltpans are reported for the first time and ideas about
      the possible survival strategies in operation have been forthcoming. The
      biochemicals produced by the cyanobacteria which colonise the interfaces between
      large plates of clear selenitic gypsum, halite, and dolomitized calcium
      carbonates in the centre of the salt pans are identifiably different from those
      which are produced by benthic cyanobacterial mats colonising the surface of the
      salt pan edges in the intertidal zone. The prediction that similar geological
      formations would have been present on early Mars and which could now be
      underlying the highly peroxidised regolith on the surface of the planet has been
      confirmed by recent satellite observations from Mars orbit and by localised
      traverses by robotic surface rovers. The successful adoption of miniaturised
      Raman spectroscopic instrumentation as part of a scientific package for detection
      of extant life or biomolecular traces of extinct life on proposed future Mars
      missions will depend critically on interpretation of data from terrestrial Mars
      analogues such as sabkhas, of which the current study is an example.

PMID- 16607493
TI  - Modeling the human PTC bitter-taste receptor interactions with bitter tastants.
AB  - We employed the first principles computational method MembStruk and homology
      modeling techniques to predict the 3D structures of the human phenylthiocarbamide
      (PTC) taste receptor. This protein is a seven-transmembrane-domain G protein
      coupled receptor that exists in two main forms worldwide, designated taster and
      nontaster, which differ from each other at three amino-acid positions. 3D models
      were generated with and without structural similarity comparison to bovine
      rhodopsin. We used computational tools (HierDock and ScanBindSite) to generate
      models of the receptor bound to PTC ligand to estimate binding sites and binding
      energies. In these models, PTC binds at a site distant from the variant amino
      acids, and PTC binding energy was equivalent for both the taster and nontaster
      forms of the protein. These models suggest that the inability of humans to taste
      PTC is due to a failure of G protein activation rather than decreased binding
      affinity of the receptor for PTC. Amino-acid substitutions in the sixth and
      seventh transmembrane domains of the nontaster form of the protein may produce
      increased steric hindrance between these two alpha-helices and reduce the motion
      of the sixth helix required for G protein activation.

PMID- 16607494
TI  - Determining functionally important amino acid residues of the E1 protein of
      Venezuelan equine encephalitis virus.
AB  - A new method for predicting interacting residues in protein complexes,
      InterProSurf, was applied to the E1 envelope protein of Venezuelan equine
      encephalitis (VEEV). Monomeric and trimeric models of VEEV-E1 were constructed
      with our MPACK program, using the crystal structure of the E1 protein of Semliki
      forest virus as a template. An alignment of the E1 sequences from representative
      alphavirus sequences was used to determine physical chemical property motifs
      (likely functional areas) with our PCPMer program. Information on residue
      variability, propensity to be in protein interfaces, and surface exposure on the
      model was combined to predict surface clusters likely to interact with other
      viral or cellular proteins. Mutagenesis of these clusters indicated that the
      predictions accurately detected areas crucial for virus infection. In addition to
      the fusion peptide area in domain 2, at least two other surface areas play an
      important role in virus infection. We propose that these may be sites of
      interaction between the E1-E1 and E1-E2 subdomains of the envelope proteins that
      are required to assemble the functional unit. The InterProSurf method is, thus,
      an important new tool for predicting viral protein interactions. These results
      can aid in the design of new vaccines against alphaviruses and other viruses.

PMID- 16607495
TI  - Automated vs. manual assessment of left ventricular function in cardiac
      multidetector row computed tomography: comparison with magnetic resonance
      imaging.
AB  - We compared semiautomatic contour detection and manual contour tracing in cardiac
      multidetector row computed tomography (MDCT) with magnetic resonance imaging
      (MRI) for calculation of left-ventricular (LV) volumes. The study included 30
      patients who underwent contrast-enhanced cardiac MDCT and cardiac cine-MRI. Were
      calculated 8 mm short-axis slices from MDCT data using three-dimensional
      multiphase image reconstruction. LV volumes including peak ejection rate and peak
      filling rate were calculated from manually and semiautomatically determined
      contours. Results were compared to those from cine-MRI with manually drawn
      contours as the standard of reference. We found good agreement for the LV
      volumes, with an ejection fraction of 47.1+/-9.4% for manually drawn contours,
      47.9+/-9.9% for semiautomatically detected contours on MDCT, and 48.0+/-10.2% for
      MRI. Except for peak-filling rate analysis of variance revealed no difference
      between any of these techniques. Bland-Altman plots and Lin's concordance
      correlation coefficient showed best agreement between MRI and manual contour
      tracing in MDCT. Calculation of LV volumes using either semiautomatic or manual
      contour tracing in cardiac MDCT is therefore feasible when compared to MRI.
      Automated contour detection needs to be improved to equal manual contour tracing.

PMID- 16607496
TI  - Quantitative magnetic resonance temperature mapping for real-time monitoring of
      radiofrequency ablation of the liver: an ex vivo study.
AB  - We evaluated the feasibility and accuracy of real-time magnetic resonance (MR)
      thermometry for monitoring radiofrequency (RF) ablation in the liver. Continuous
      MR temperature mapping was used to monitor bipolar RF ablations performed in ex
      vivo livers with and without flow using two parallel electrodes. Macroscopic
      inspection of ablation zones was compared with thermal dose maps (TDm) and T1
      weighted inversion recovery turbo spin echo (IR-TSE) images for their size and
      shape and the influence of flow. Pearson's correlation (r), Bland and Altman
      tests and kappa (chiK) tests were performed. The mean differences in ablation
      zone size between macroscopic and TDm and IR-TSE measurements were +4 mm and -2
      mm, respectively. TDm was well correlated with macroscopy (r=0.77 versus r=0.44
      for IR-TSE). TDm was found to be more precise for shape recognition (chiK=0.73
      versus chiK=0.55 for IR-TSE) and for detection of an intact ring of liver due to
      the cooling effect of flow which was impossible with IR-TSE. Simultaneous
      monitoring of RF ablation by MR thermometry is feasible and reliable for
      predicting the shape of ablation zones and the impact of the heat-sink effect of
      flow. Further studies are needed to confirm these results in vivo.

PMID- 16607498
TI  - A boy with acute urinary retention: a Mullerian duct remnant (2006: 3b).
AB  - Vestiges of the Mullerian duct systems are found in the male and these may
      occasionally give rise to symptoms. We report a case of acute urinary retention
      in a male child secondary to a Mullerian duct remnant. Subsequent MRI was done to
      reach the final diagnosis.

PMID- 16607497
TI  - Endoleakage after endovascular treatment of abdominal aortic aneurysms:
      Diagnosis, significance and treatment.
AB  - Endoleak, also called leakage, leak and Perigraft leak, is a major complication
      and its persistence represents a failure of endovascular aortic aneurysm repair.
      Its detection and treatment is therefore of primary importance, since endoleak
      can be associated with pressurization (increase in pressure) of the sac,
      resulting in expansion and rupture of the aneurysm. The aim of this paper is to
      discuss the definition, significance, diagnosis and different options to treat
      endoleak.

PMID- 16607500
TI  - An unusual cause of intermittent abdominal pain (2006: 5a).

PMID- 16607499
TI  - Influence of cardiac hemodynamic parameters on coronary artery opacification with
      64-slice computed tomography.
AB  - The purpose of this study was to evaluate the influence of ejection fraction
      (EF), stroke volume (SV), heart rate, and cardiac output (CO) on coronary artery
      opacification with 64-slice computed tomography (CT). Sixty patients underwent,
      retrospectively, electrocardiography-gated 64-slice CT coronary angiography. Left
      ventricular EF, SV, and CO were calculated with semi-automated software.
      Attenuation values were measured and contrast-to-noise ratios (CNRs) were
      calculated in the proximal right coronary artery (RCA) and left main artery
      (LMA). Mean EF during scanning was 61.5+/-12.4%, SV was 63.2+/-15.6 ml, heart
      rate was 62.5+/-11.8 beats per minute (bpm), and CO was 3.88+/-1.06 l/min. There
      was no significant correlation between the EF and heart rate and the attenuation
      and CNR in either coronary artery. A significant negative correlation was found
      in both arteries between SV and attenuation (RCA r=-0.26, P<0.05; LMA r=-0.34,
      P<0.01) and between SV and CNR (RCA r=-0.26, P<0.05; LMA r=-0.26, P<0.05).
      Similarly, a significant negative correlation was found between the CO and
      attenuation (RCA r=-0.42, P<0.05; LMA r=-0.56, P<0.001) and between the CO and
      CNR (RCA r=-0.39, P<0.05; LMA r=-0.44, P<0.001). The actual hemodynamic status of
      the patient influences the coronary artery opacification with 64-slice CT, in
      that vessel opacification decreases as SV and CO increase.

PMID- 16607503
TI  - [Histological findings for human tibial bone-tendon healing after hamstring
      transplantation. Investigation of tibial insertion after reconstruction of
      anterior cruciate ligaments with hamstring transplantation near joint fixation
      using bioresorbable interference screws].
AB  - Ruptures of hamstring reconstructed anterior cruciate ligaments required
      additional surgery in five cases over a 4 year period. All transplants were
      primarily fixed with bioresorbable interference screws close to the joint. The
      average age was 31 years (range: 18-42), the average interval between primary
      surgery and rupture of the transplant was 13.2 months (range: 8-24) after an
      adequate re-trauma. After complete removal of the tibial insertion, a
      histological investigation was carried out. We stained the tissue-sections
      following the haematoxylin-eosin, Masson-Goldner and van Gieson protocols. All
      cases revealed direct healing with grow-over Sharpey-like fibers close to the
      joint, corresponding to a fibrous tendon insertion and far from the joint the
      formation of fibrous or cartilage callus.

PMID- 16607504
TI  - [A 19-year-old patient with acute promyelocytic leukemia and knee swelling].
AB  - We report on a case of a 19-year-old female patient with acute promyelocytic
      leukemia suffering from febrile monarthitis of the right knee during neutropenia
      after consolidation chemotherapy caused by Geotrichum capitatum. Apparently this
      infection occurred due to a hematological reactivation since the patient had
      already developed Geotrichum capitatum fungemia during induction therapy. Under
      antimycotic therapy with voriconazole, flucytosine, and caspofungin as well as
      after two arthroscopic synovectomies with cleansing of the right knee, the
      infection could be controlled and the full clinical function of the knee joint
      could be preserved.

PMID- 16607505
TI  - [Optimized auricular reconstruction with autologous cartilage. Experience from
      120 cases].
AB  - INTRODUCTION: Auricular reconstruction with autologous cartilage has become well
      established in the last decade. By optimizing the technique, both the results and
      reliability have improved. OPERATION AND RESULTS: Based on our experience with
      120 cases, we developed a concept that allows total ear reconstruction in two
      surgical steps. In the first operation, autologous rib cartilage is harvested and
      a natural framework created following the template of the opposite ear. The ear
      remnant is transposed and the framework placed in a subcutaneous pocket on the
      mastoid plane. After a healing period of around 6 weeks, the second operation
      reconstructs the auricular projection and the postauricular fold. The surgical
      procedure has to be adapted to difficult soft tissue situations. Most important
      is the specific analysis of local tissue and its resulting limitations. Deep
      scaring and skin grafting from previous operations need coverage of the framework
      with a subgaleal fascia flap. CONCLUSION: This optimized and adapted surgical
      procedure allows auricular reconstruction with autologous rib cartilage from the
      age of around 8 years into old age with good, reproducible results.

PMID- 16607507
TI  - Gomez-Lopez-Hernandez syndrome.
AB  - We describe a case of Gomez-Lopez-Hernandez syndrome in an 18-month-old boy.
      Imaging findings included rhombencephalosynapsis with a single dentate nucleus.
      In addition, MR angiography revealed an azygous anterior cerebral artery. The
      clinical presentation, MRI findings and pathogenesis are discussed.

PMID- 16607506
TI  - Structure and function of glucose-6-phosphate dehydrogenase-deficient variants in
      Chinese population.
AB  - A systematic study on the structure and function of Glucose-6-phosphate
      dehydrogenase (G6PD) variations was carried out in China. A total of 155,879
      participants were screened for G6PD deficiency by the G6PD/6PGD ratio method and
      6,683 cases have been found. The prevalence of G6PD deficiency ranged from 0 to
      17.4%. With informed consent, 1,004 cases from 11 ethnic-based groups were
      subjected to molecular analysis. Our results showed the followings: (1) The G6PD
      variants are consistent across traditional ethnic boundaries, but vary in
      frequencies across ethnic-based groups in Chinese population, (2) The G6PD
      variants in Chinese population are different from those in African, European, and
      Indian populations, (3) A novel G6PD-deficiency mutation, 274C-->T, has been
      found, and (4) Denaturing high performance liquid chromatography is of great
      advantage to detecting G6PD-deficient mutations for diagnosis and genetic
      counseling. Moreover, functional analysis of the human G6PD variants showed the
      following: (1) The charge property, polarity, pK-radical and side-chain radical
      of the substituting amino acid have an effect on G6PD activity, (2) The
      G6PDArg459 and Arg463 play important roles in anchoring NADP+ to the catalytic
      domain to maintain the enzymatic activity, and (3) The sequence from codon 459 to
      the carboxyl terminal is essential for the enzymatic function.

PMID- 16607508
TI  - Clinical image. Transection of the spinal cord: a rare birth-related trauma.

PMID- 16607509
TI  - Chromosome territory positioning of conserved homologous chromosomes in different
      primate species.
AB  - Interphase chromosomes form distinct spatial domains called chromosome
      territories (CTs). The position of CTs is known not to be at random and is
      related to chromosome size and gene density. To elucidate how CTs are arranged in
      primate proliferating fibroblasts and whether the radial position of CTs has been
      conserved during primate evolution, several specific CTs corresponding to
      conserved chromosomes since the Simiiformes (human 6, 12, 13, and 17 homologous
      CTs) have been studied in 3D preserved interphase nuclei from proliferant cells
      of two New World monkey species (Lagothrix lagothricha, Saimiri sciureus) and in
      human by three-dimensional fluorescent in situ hybridization (3D-FISH). Our
      results indicate that both gene-density and chromosome size influence chromosome
      territory arrangement in the nucleus. This influence is greater for chromosome
      size than for gene-density in the three species studied. A comparison of the
      radial position of a given CT and its homolog in the species analyzed suggests
      similar CT distributions for homologous chromosomes. Our statistical analysis
      using the logit model shows that such homologous positionings cannot, however, be
      considered identical.

PMID- 16607510
TI  - The origin, meiotic behavior, and transmission of a novel minichromosome in
      Arabidopsis thaliana.
AB  - A plant carrying a small extra chromosome was found in Landsberg erecta ecotype
      of Arabidopsis thaliana. Fluorescence in situ hybridization revealed that this
      minichromosome was derived from the short arm of chromosome 4. The size of this
      "mini4S" chromosome was estimated to be approximately 7.5 Mb on the basis of
      previously reported data and the amount of the centromeric major satellite (180
      bp family) present, which was determined to be about 1 Mb, or about one third of
      that in the normal chromosome 4. No pairing between mini4S and its original
      chromosome 4 was observed at pachytene and metaphase I stages. The transmission
      of mini4S through pollen was limited, but about 30% of selfed progeny carried the
      mini4S chromosomes. The transmission rates considerably increased when the mini4S
      chromosomes were transferred to plants with a Columbia background by successive
      backcrosses. This suggests that the stability of the minichromosomes is
      controlled genetically by factors that can vary between ecotypes.

PMID- 16607512
TI  - Amaranth decoloration by Trametes versicolor in a rotating biological contacting
      reactor.
AB  - Sequential batch and continuous operation of a rotating biological contacting
      (RBC) reactor and the effects of dissolved oxygen on the decoloration of amaranth
      by Trametes versicolor were evaluated. Amaranth belongs to the group of azo dyes
      which are potential carcinogens and/or mutagens that can be transformed into
      toxic aryl amines under anaerobic conditions. Cultivation of T. versicolor in a
      stirred tank reactor was found to be unsuitable for amaranth decoloration due to
      significant biomass fouling and increase in medium viscosity. Assuming that
      decoloration follows first-order kinetics, amaranth was decolorized more rapidly
      when T. versicolor was immobilized on jute twine in a RBC reactor operated either
      in a sequential batch (k=0.25 h(-1)) or in a continuous (0.051 h(-1)) mode
      compared to a stirred tank reactor (0.015 h(-1)). Oxygen was found to be
      essential for decoloration with the highest decoloration rates occurring at
      oxygen saturation. Although longer retention times resulted in more decoloration
      when the RBC was operated in the continuous mode (about 33% amaranth
      decoloration), sequential batch operation gave better results (>95%) under
      similar nutrient conditions. Our data indicate that the fastest decoloration
      should occur in the RBC using nitrogen-free Kirk's medium with 1 g/l glucose in
      sequential batch operation at rotational speeds and/or aeration rates which
      maintain oxygen saturation in the liquid phase.

PMID- 16607511
TI  - The SuUR gene influences the distribution of heterochromatic proteins HP1 and
      SU(VAR)3-9 on nurse cell polytene chromosomes of Drosophila melanogaster.
AB  - We have investigated the distribution of three heterochromatic proteins
      [SUppressor of UnderReplication (SUUR), heterochromatin protein 1 (HP1), and
      SU(VAR)3-9] in chromosomes of nurse cells (NCs) and have compared the data
      obtained with the distribution of the same proteins in salivary gland (SG)
      chromosomes. In NC chromosomes, the SU(VAR)3-9 protein was found in pericentric
      heterochromatin and at 223 sites on euchromatic arms, while in SG chromosomes, it
      was mainly restricted to the chromocenter. In NC chromosomes, the HP1 and SUUR
      proteins bind to 331 and 256 sites, respectively, which are almost twice the
      number of sites in SG chromosomes. The distribution of the HP1 and SU(VAR)3-9
      proteins depends on the SuUR gene. A mutation in this gene results in a dramatic
      decrease in the amount of SU(VAR)3-9 binding sites in autosomes. In the X
      chromosome, these sites are relocated in comparison to the SuUR (+), and their
      total number only varies slightly. HP1 binding sites are redistributed in
      chromosomes of SuUR mutants, and their overall number did not change as
      considerably as SU(VAR)3-9. These data together point to an interaction of these
      three proteins in Drosophila NC chromosomes.

PMID- 16607513
TI  - Genome-wide isolation of resistance gene analogs in maize (Zea mays L.).
AB  - Conserved domains or motifs shared by most known resistance (R) genes have been
      extensively exploited to identify unknown R-gene analogs (RGAs). In an attempt to
      isolate all potential RGAs from the maize genome, we adopted the following three
      methods: modified amplified fragment length polymorphism (AFLP), modified rapid
      amplification of cDNA ends (RACE), and data mining. The first two methods
      involved PCR-based isolations of RGAs with degenerate primers designed based on
      the conserved NBS domain; while the third method involved mining of RGAs from the
      maize EST database using full-length R-gene sequences. A total of 23 and 12 RGAs
      were obtained from the modified AFLP and RACE methods, respectively; while, as
      many as 109 unigenes and 77 singletons with high homology to known R-genes were
      recovered via data-mining. Moreover, R-gene-like ESTs (or RGAs) identified from
      the data-mining method could cover all RACE-derived RGAs and nearly half AFLP
      derived RGAs. Totally, the three methods resulted in 199 non-redundant RGAs. Of
      them, at least 186 were derived from putative expressed R-genes. RGA-tagged
      markers were developed for 55 unique RGAs, including 16 STS and 39 CAPS markers.

PMID- 16607514
TI  - Genetic linkage map of the interspecific grape rootstock cross Ramsey (Vitis
      champinii) x Riparia Gloire (Vitis riparia).
AB  - The first genetic linkage map of grape derived from rootstock parents was
      constructed using 188 progeny from a cross of Ramsey (Vitis champinii) x Riparia
      Gloire (V. riparia). Of 354 simple sequence repeat markers tested, 205 were
      polymorphic for at least one parent, and 57.6% were fully informative. Maps of
      Ramsey, Riparia Gloire, and the F1 population were created using JoinMap
      software, following a pseudotestcross strategy. The set of 205 SSRs allowed for
      the identification of all 19 Vitis linkage groups (2n=38), with a total combined
      map length of 1,304.7 cM, averaging 6.8 cM between markers. The maternal map
      consists of 172 markers aligned into 19 linkage groups (1,244.9 cM) while 126
      markers on the paternal map cover 18 linkage groups (1,095.5 cM). The expected
      genome coverage is over 92%. Segregation distortion occurred in the Ramsey,
      Riparia Gloire, and consensus maps for 10, 13, and 16% of the markers,
      respectively. These distorted markers clustered primarily on the linkage groups
      3, 5, 14 and 17. No genome-wide difference in recombination rate was observed
      between Ramsey and Riparia Gloire based on 315 common marker intervals. Fifty
      four new Vitis-EST-derived SSR markers were mapped, and were distributed evenly
      across the genome on 16 of the 19 linkage groups. These dense linkage maps of two
      phenotypically diverse North American Vitis species are valuable tools for
      studying the genetics of many rootstock traits including nematode resistance,
      lime and salt tolerance, and ability to induce vigor.

PMID- 16607516
TI  - [Identification of surgical patients for therapy with activated Drotrecogin
      alfa].
AB  - There is uncertainty whether surgical patients with severe sepsis have a benefit
      from therapy with Drotrecogin alfa (activated). In the PROWESS and ENHANCE
      studies 4,068 patients were included and 3,228 were treated with Drotrecogin alfa
      (activated). Approximately 28% of the PROWESS patients and 41% of the ENHANCE
      patients were surgical patients. The subgroup of surgical patients showed the
      same benefit from therapy with Drotrecogin alfa (activated) as the overall
      cohort. The relative risk was 0.9 (95% CI 0.7-1.25, absolute risk reduction
      3.2%). Patients with intraabdominal infections have a special benefit and here
      the relative risk was 0.7 (95% CI 0.5-1.0, absolute risk reduction 9.1%). Serious
      bleeding was more frequent in patients treated with Drotrecogin alfa (activated):
      2.4-3.6% vs. 1.0% in the placebo group. In surgical patients bleeding was not
      more frequent than in non-surgical patients (3.1% vs. 2.1%, difference not
      significant). Surgical patients with severe sepsis, especially with peritonitis,
      should receive therapy with Drotrecogin alfa (activated), if severely ill.

PMID- 16607517
TI  - A specific catalytic subunit isoform of protein kinase CK2 is required for
      phosphorylation of the repressor Nrg1 in Saccharomyces cerevisiae.
AB  - Protein kinase CK2 is highly conserved in eukaryotes and plays roles in many
      different cellular processes. CK2 is a tetramer comprising two catalytic and two
      regulatory subunits. Most organisms have two major isoforms of the catalytic
      subunit, and evidence suggests strongly overlapping function. In the yeast
      Saccharomyces cerevisiae, CK2 is essential for viability, and either catalytic
      subunit isoform, Cka1 or Cka2, suffices, but previous genetic evidence suggests
      that the isoforms have some distinct roles. In this work, we present evidence
      that the transcriptional repressor Nrg1, which regulates various stress
      responsive genes, is a downstream target of CK2 containing the Cka1 isoform. We
      found that Nrg1 is phosphorylated in response to stress and that its
      phosphorylation was defective in cka1Delta, but not cka2Delta, mutants. Thus, the
      Cka1 catalytic subunit isoform is specifically required for phosphorylation of
      Nrg1 in vivo. The CK2 regulatory subunits were also required, indicating that the
      CK2 holoenzyme is involved. Both yeast and recombinant human CK2 phosphorylated
      recombinant Nrg1 in vitro. This identification of a protein whose phosphorylation
      requires a specific CK2 catalytic subunit isoform supports the view that the two
      isoforms exhibit functional specificity in vivo.

PMID- 16607519
TI  - [Nuclear medicine techniques in the diagnosis of orthopaedic diseases].
AB  - Nuclear medicine techniques show metabolic processes, allowing the diagnoses of
      many bone and joint disorders. For most orthopaedic indications three-phase bone
      scintigraphy is used, showing inflammatory bone and joint diseases, traumatic and
      post-operative disorders as well as necrotic or malignant changes. In addition to
      bone scintigraphy, there are radiopharmaceuticals to depict inflammatory
      processes. Finally, positron emission tomography is a modern imaging technique
      used mainly for tumor diagnostics, but also for detection of inflammation.

PMID- 16607520
TI  - The morbidity and outcome of surgery in children with large pre-treated Wilms'
      tumour: size matters.
AB  - Sixty-seven patients with resected Wilms' tumour>1.0 kg are reported. Surgery in
      this group is difficult, may result in the sacrifice of adjacent structures, and
      frequently upstages the patient. Mortality is related to tumour burden. Whilst
      there is little agreement on the therapeutic implications of failure to respond
      to neoadjuvant therapy, these surgical and anaesthetic hazards must be
      recognized, and alternative stratagems considered, prior to attempting a surgical
      procedure.

PMID- 16607518
TI  - [Nutrition, lifestyle, physical activity, and supportive care during
      chemotherapeutic treatment].
AB  - With improvements in cancer survival rates, more patients with cancer are living
      longer and the influence of nutrition, lifestyle, physical activity as well as
      supportive care during and after chemotherapy is of increasing interest. In
      several malignancies smoking cessation increases cancer survival. Similar effects
      are expected by healthy nutrition. Regular physical activity of cancer patients
      reduces drug interactions of chemotherapy, decreases the number of comorbid
      conditions, and helps patients maintain independence as long as possible. For
      supportive care during chemotherapy the 5-HT3 receptor antagonists are more
      effective for the prevention of chemotherapy-induced nausea and vomiting. There
      are several colony-stimulating factors (e.g. GCSF, erythropoietin) for
      hematopoietic recovery post-chemotherapy. Altogether supportive care of
      chemotherapy reduces toxicity and increases efficacy.

PMID- 16607521
TI  - Riboflavin analogs and inhibitors of riboflavin biosynthesis.
AB  - Flavins are active components of many enzymes. In most cases, riboflavin (vitamin
      B(2)) as a coenzyme represents the catalytic part of the holoenzyme. Riboflavin
      is an amphiphatic molecule and allows a large variety of different interactions
      with the enzyme itself and also with the substrate. A great number of active
      riboflavin analogs can readily be synthesized by chemical methods and, thus, a
      large number of possible inhibitors for many different enzyme targets is
      conceivable. As mammalian and especially human biochemistry depends on flavins as
      well, the target of the inhibiting flavin analog has to be carefully selected to
      avoid unwanted effects. In addition to flavoproteins, enzymes, which are involved
      in the biosynthesis of flavins, are possible targets for anti-infectives. Only a
      few flavin analogs or inhibitors of flavin biosynthesis have been subjected to
      detailed studies to evaluate their biological activity. Nevertheless, flavin
      analogs certainly have the potential to serve as basic structures for the
      development of novel anti-infectives and it is possible that, in the future, the
      urgent need for new molecules to fight multiresistant microorganisms will be met.

PMID- 16607522
TI  - Development of enzyme flow calorimeter system for monitoring of microbial
      glycerol conversion.
AB  - Glycerokinase from Cellulomonas sp. was used to develop biosensor based on flow
      calorimetry for quantitative analysis of glycerol during bioconversion process.
      An automatic flow injection analysis device with the glycerol biosensor was built
      and tested during growth on glycerol of 1,3-propanediol-producing bacteria. The
      biosensor exhibited an extreme storage and operational stability enabling us to
      use it for more than 2 years without significant loss of sensitivity. No
      interference with 1,3-propanediol and fermentation medium was observed. The
      linear range of glycerol concentration up to 70 mM was extended by developed
      automatic dilution technique with the aim of automatic online monitoring of
      microbial process. The analytical system was able to monitor the bioconversion
      process in a fully automatic way during the whole run with sampling frequency of
      one sample per 10 min.

PMID- 16607523
TI  - Characterization of a recombinant thermostable xylanase from deep-sea
      thermophilic Geobacillus sp. MT-1 in East Pacific.
AB  - A novel xylanase-producing thermophilic strain MT-1 was isolated from a deep-sea
      hydrothermal field in east Pacific. A xylanase gene encoding 331 amino-acid
      peptide from this isolate was cloned and expressed in Escherichia coli. The
      recombinant xylanase exhibited maximum activity at 70 degrees C and had an
      optimum pH of 7.0. It was active up to 90 degrees C and showed activity over a
      wide pH ranging from 5.5 to 10.0. The crude xylanase presented similar properties
      in temperature and pH to those of the recombinant xylanase. The recombinant
      xylanase was stable in 1 mM of enzyme inhibitors (PMSF, EDTA, 2-ME or DTT) and in
      0.1% detergents (Tween 20, Chaps or Triton X-100), whereas, it was strongly
      inhibited by sodium dodecyl sulfate (SDS) (1 mM). In addition, its catalytic
      function was stable in the presence of Li(+), Na(+) or K(+). However, it was
      strongly inhibited by Ni(2+), Mn(2+), Co(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+) and
      Al(3+) (1 or 0.1 mM). The K (m) and V (max) of the recombinant xylanase for oat
      spelt xylan were calculated to be 1.579 mg/ml and 289 micromol/(min x mg),
      respectively. Our study, therefore, presented a rapid overexpression and
      purification of xylanase from deep-sea thermophile aimed at improving the enzyme
      yield for industrial applications and scientific research.

PMID- 16607524
TI  - Biodegradation of phthalate isomers by Pseudomonas aeruginosa PP4, Pseudomonas
      sp. PPD and Acinetobacter lwoffii ISP4.
AB  - Pseudomonas aeruginosa PP4, Pseudomonas sp. PPD and Acinetobacter lwoffii ISP4
      capable of utilizing phthalate isomers were isolated from the soil using
      enrichment culture technique. The strain ISP4 metabolizes isophthalate, while PPD
      and PP4 utilizes all three phthalate isomers (ortho-, iso- and tere-) as the sole
      carbon source. ISP4 utilizes isophthalate (0.1%) more rapidly (doubling time, 0.9
      h) compared to PPD (4.64 h), PP4 (7.91 h) and other reported strains so far. The
      metabolic pathways in these isolates were initiated by dihydroxylation of
      phthalate isomers. Phthalate is hydroxylated to 3,4-dihydro-3,4
      dihydroxyphthalate and 4,5-dihydro-4,5-dihydroxyphthalate in strains PP4 and PPD,
      respectively; while terephthalate is hydroxylated to 2-hydro-1,2
      dihydroxyterephthalate. All three strains hydroxylate isophthalate to 4-hydro-3,4
      dihydroxyisophthalate. The generated dihydroxyphthalates were subsequently
      metabolized to 3,4-dihydroxybenzoate (3,4-DHB) which was further metabolized by
      ortho ring-cleavage pathway. PP4 and PPD cells grown on phthalate, isophthalate
      or terephthalate showed respiration on respective phthalate isomer and the
      activity of corresponding ring-hydroxylating dioxygenase, suggesting the carbon
      source specific induction of three different ring-hydroxylating dioxygenases. We
      report, for the first time, the activity of isophthalate dioxygenase and its
      reductase component in the cell-free extracts. The enzyme showed maximum activity
      with reduced nicotinamide adenine dinucleotide (NADH) in the pH range 8-8.5.
      Cells grown on glucose failed to respire on phthalate isomers and 3,4-DHB and
      showed significantly low activities of the enzymes suggesting that the enzymes
      are inducible.

PMID- 16607525
TI  - Analysis of the genomic response of a wine yeast to rehydration and inoculation.
AB  - We used DNA microarrays to study the transcriptome of a wine yeast before and
      after rehydration and during the first hours following inoculation of a synthetic
      must. There was a substantial transcriptional remodeling during this period,
      including 1,874 genes regulated more than threefold. Dried yeasts displayed an
      expression profile typical of respiratory-grown cells starved for nitrogen and
      carbon and which had been highly stressed. During rehydration, many genes
      involved in biosynthetic pathways, in transcription or in protein synthesis were
      coordinately induced while genes subject to glucose repression were down
      regulated. The transcriptional response was very rapid indicating that yeast
      quickly recovered the capacity to sense environmental signals and to respond
      appropriately. Our data show that genes involved in the general stress response
      were repressed during rehydration while acid stress specific genes were induced
      probably in response to organic acid accumulation. The glycolytic genes and acid
      stress-responsive genes were simultaneously and transiently repressed after
      inoculation into the fermentation medium suggesting that regulation of glycolytic
      genes may correspond to an adjustment to the energetic needs of the cells.
      Surprisingly, inoculation into the must did not trigger a stress response despite
      the high concentrations of sugars.

PMID- 16607526
TI  - Influence of extrinsic factors on granulation in UASB reactor.
AB  - The aim of this mini-review is to synthesize and analyze information on how the
      process of granulation is affected by environmental and operational conditions in
      the reactor. The factors reviewed are temperature, pH, alkalinity, organic
      loading rate, upflow velocity, nature and strength of substrate, nutrients,
      multivalent cations and heavy metals, microbial ecology of seed sludge, exo
      cellular polymer, and addition of natural and synthetic polymers. Careful
      temperature control and adequate alkalinity is required for generation and
      maintenance of granules. Nature and strength of substrate in conjunction with
      intra-granular diffusion to a large extent determines the microstructure of the
      granules. The divalent cations such as calcium and iron may enhance granulation
      by ionic bridging and linking exo-cellular polymers. However, their presence in
      excess may lead to cementation due to precipitation leading to increased ash
      content and mass transfer limitation. The addition of external additives such as
      ionic polymers may enhance granulation in the upflow anaerobic sludge blanket
      reactors.

PMID- 16607527
TI  - In situ product recovery (ISPR) by crystallization: basic principles, design, and
      potential applications in whole-cell biocatalysis.
AB  - The removal of inhibiting or degrading product from a bioreactor as soon as the
      product is formed is an important issue in industrial bioprocess development. In
      this review, the potential of crystallization as an in situ product removal
      (ISPR) technique for the biocatalytic production of crystalline compounds is
      discussed. The emphasis of this review is on the current status of crystalline
      product formation by metabolically active cells for application in fine-chemicals
      production. Examples of relevant biocatalytic conversions are summarized, and
      some basic process options are discussed. Furthermore, a case study is presented
      in which two conceptual process designs are compared. In one process, product
      formation and crystallization are integrated by applying ISPR, whereas a second,
      nonintegrated process is based on a known conventional process equivalent for the
      production of 6R-dihydro-oxoisophorone. The comparison indicates that employing
      ISPR leads to significant advantages over the nonintegrated case in terms of
      increased productivity and yield with a corresponding decrease in the number of
      downstream processing steps, as well as in the quantity of waste streams. This
      leads to an economically more interesting process alternative. Finally, a general
      outlook on the various research aspects of ISPR by crystallization is given.

PMID- 16607528
TI  - Regulation of polyhydroxyalkanoate synthases (phaC1 and phaC2) gene expression in
      Pseudomonas corrugata.
AB  - In this study we examined polyhydroxyalkanoate (PHA) synthases phaC1 and phaC2
      gene expression in two strains of Pseudomonas corrugata (Pc) grown in a minimum
      mineral medium with related (oleic acid and octanoate) or unrelated (glucose)
      carbon sources. Analysis of transcription was performed by Northern blot and
      conventional reverse transcriptase (RT) polymerase chain reaction (PCR). In
      addition, we developed a RT-real-time PCR method to quantitatively evaluate phaC1
      (Pc) and phaC2 (Pc) gene expression. Primers and a TaqMan probe were designed for
      the specific detection of both synthase transcripts as well as of the
      housekeeping 16S rRNA, and the relative expression of target genes was
      calculated. We showed that phaC1 (Pc) and phaC2 (Pc) were not cotranscribed and,
      on the contrary, were independently regulated. In cultures grown with oleic acid
      as the sole carbon source, only the expression of phaC1 (Pc) was induced (a
      tenfold increase after 72 h of culture), whereas that of phaC2 (Pc) remained
      unchanged. In cultures grown with glucose or sodium octanoate, the expression of
      both phaC1 (Pc) and phaC2 (Pc) was upregulated but at different rates. Cellular
      PHA content was compared to the gene expression of the PHA synthases and
      significant correlations were found between PHA production and phaC1 (Pc)/phaC2
      (Pc) expression.

PMID- 16607529
TI  - Cloning, expression, and characterization of a self-sufficient cytochrome P450
      monooxygenase from Rhodococcus ruber DSM 44319.
AB  - A new member of class IV of cytochrome P450 monooxygenases was identified in
      Rhodococcus ruber strain DSM 44319. As the genome of R. ruber has not been
      sequenced, a P450-like gene fragment was amplified using degenerated primers. The
      flanking regions of the P450-like DNA fragment were identified by directional
      genome walking using polymerase chain reaction. The primary protein structure
      suggests a natural self-sufficient fusion protein consisting of ferredoxin,
      flavin-containing reductase, and P450 monooxygenase. The only flavin found within
      the enzyme was riboflavin 5'-monophosphate. The enzyme was successfully expressed
      in Escherichia coli, purified and characterized. In the presence of NADPH, the
      P450 monooxygenase showed hydroxylation activity towards polycyclic aromatic
      hydrocarbons naphthalene, indene, acenaphthene, toluene, fluorene, m-xylene, and
      ethyl benzene. The conversion of naphthalene, acenaphthene, and fluorene resulted
      in respective ring monohydroxylated metabolites. Alkyl aromatics like toluene, m
      xylene, and ethyl benzene were hydroxylated exclusively at the side chains. The
      new enzyme's ability to oxidize such compounds makes it a potential candidate for
      biodegradation of pollutants and an attractive biocatalyst for synthesis.

PMID- 16607530
TI  - Purification and molecular characterization of cold-active beta-galactosidase
      from Arthrobacter psychrolactophilus strain F2.
AB  - In this study, we purified and molecularly characterized a cold-active beta
      galactosidase from Arthrobacter psychrolactophilus strain F2. The purified beta
      galactosidase from strain F2 exhibited high activity at 0 degrees C, and its
      optimum temperature and pH were 10 degrees C and 8.0, respectively. It was
      possible to inactivate the beta-galactosidase rapidly at 45 degrees C in 5 min.
      The enzyme was able to hydrolyze lactose as a substrate, as well as o-nitrophenyl
      beta-D-galactopyranoside (ONPG), the Km values with ONPG and lactose being
      calculated to be 2.8 mM and 50 mM, respectively, at 10 degrees C. Moreover, the
      bglA gene encoding the beta-galactosidase of strain F2 was cloned and analyzed.
      The bglA gene consists of a 3,084-bp open reading frame corresponding to a
      protein of 1,028 amino acid residues. BglAp, the gene product derived from bglA,
      had several conserved regions for glycosyl hydrolase family 2, e.g., the glycosyl
      hydrolase 2 (GH2) sugar binding domain, GH2 acid-base catalyst, GH2
      triosephosphate isomerase barrel domain, GH2 signature 1, and several other GH2
      conserved regions. From these facts, we conclude that the beta-galactosidase from
      A. psychrolactophilus strain F2, which is a new member of glycosyl hydrolase
      family 2, is a cold-active enzyme that is extremely heat labile and could have
      advantageous applications in the food industry.

PMID- 16607531
TI  - Development of transgenic pearl millet (Pennisetum glaucum (L.) R. Br.) plants
      resistant to downy mildew.
AB  - Transgenic pearl millet lines expressing pin gene--exhibiting high resistance to
      downy mildew pathogen, Sclerospora graminicola--were produced using particle
      inflow-gun (PIG) method. Shoot-tip-derived embryogenic calli were co-bombarded
      with plasmids containing pin and bar genes driven by CaMV 35S promoter. Bombarded
      calli were cultured on MS medium with phosphinothricin as a selection agent.
      Primary transformants 1T(0), 2T(0), and 3T(0) showed the presence of both bar and
      pin coding sequences as evidenced by PCR and Southern blot analysis,
      respectively. T(1) progenies of three primary transformants, when evaluated for
      downy mildew resistance, segregated into resistant and susceptible phenotypes.
      T(1) plants resistant to downy mildew invariably exhibited tolerance to Basta
      suggesting co-segregation of pin and bar genes. Further, the downy mildew
      resistant 1T(1) plants were found positive for pin gene in Southern and Northern
      analyses thereby confirming stable integration, expression, and transmission of
      pin gene. 1T(2) progenies of 1T(0) conformed to dihybrid segregation of 15
      resistant:1 susceptible plants.

PMID- 16607532
TI  - Vascular complications of cranial radiation.
AB  - OBJECTIVES: Cerebral vascular disease has been reported as a long-term
      complication of cranial radiotherapy. The purpose of this study was to examine
      the frequency and risk factors associated with development of cerebral vascular
      disease in children after cranial radiation. MATERIALS AND METHODS: A
      retrospective chart review of all cancer patients treated between 1985 and 2003
      who were under the age of 18 years at the time of initial radiotherapy was
      performed. Variables examined include diagnosis and site of malignancy, age at
      the time of radiotherapy, sex, total radiation dosage, number of fractions,
      duration, and whether the patient had proven cerebral vascular event. RESULTS:
      Two hundred and forty-four patients met the study criteria. One hundred and 13
      cases involved tumors of the central nervous system. The remaining patients had
      systemic neoplastic disease. Post radiation cerebral vascular disease occurred in
      11 (5%) patients, and all but one patient had a tumor involving the central
      nervous system (mainly in the posterior fossa and supratentorial midline).
      CONCLUSION: There is an increased risk of cerebral vascular disease after
      radiation therapy in childhood, especially in children who received high dose
      radiation at the posterior fossa and supratentorial axial region.

PMID- 16607533
TI  - Malignant disseminated chordoid meningioma in a 12-year-old child: a role for
      early cranial and spinal radiation treatment after subtotal resection.
AB  - CASE REPORT: We present a case of a chordoid meningioma, a tumour sub-type which
      comprises less than 0.5% of all meningiomas. The patient, a 12-year-old Somalian
      girl with a history of having had a craniotomy for a brain tumour in her native
      country 11 months previously, presented with seizures. Imaging revealed an
      isolated left frontal tumour, which at the time was felt to be a residual mass.
      She underwent a macroscopically complete resection of this tumour. Histology
      revealed it to be a grade 2 chordoid meningioma. Recurrence with additional local
      meningeal lesions was detected on follow-up magnetic resonance imaging (MRI) at 2
      months post surgery. These were resected and she was treated with adjuvant
      cranial radiation treatment that resulted in non-progression of the cranial
      tumour on imaging 6 and 12 months post surgery. However, at 12 months post
      initial presentation, she re-presented with disseminated spinal disease
      refractory to salvage radiation treatment and succumbed to her illness. OUTCOME:
      This is the first reported case of cranial radiation treatment being used to
      treat sub-totally resected recurrent chordoid meningioma. Whilst intra-cranial
      control of the tumour was achieved with this management, it did not prevent
      spinal progression. The authors advise a high-surveillance management strategy
      when treating these lesions and to employ cranial and spinal radiation treatment
      at the first sign of disease progression.

PMID- 16607534
TI  - Diagnosis and management of cerebral salt wasting (CSW) in children: the role of
      atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP).
AB  - OBJECTIVE: The aim of this study is to report our experience with diagnosis and
      management of cerebral salt wasting (CSW) in children and to evaluate the role of
      atrial natriuretic peptide/brain natriuretic peptide (ANP/BNP) in pediatric
      patients. MATERIALS AND METHODS: We present nine children suffering from
      prevalent cerebral disease--seven of whom underwent anesthesia and surgical
      procedures--with features of CSW, seen within a 22-month period. The symptoms,
      patient characteristics (including hormone status), monitoring, treatment
      protocol, and outcome are described. RESULTS: Natriuresis (urine Na+
      concentrations 131 to >250 mmol/l) and polyuria (5.5+/-1.5 ml/kg/h) with
      increased Na+ turnover (maximum Na+ loss: median 1.50 mmol Na+/kg/h, range 0.47
      to >3.50) vanished within 2 weeks in 6/9 patients (increase in serum Na+ from
      127+/-2 mmol/l to 136+/-1). K+ excretion was also high (maximum K+ loss: median
      0.18 mmol K+/kg/h, range 0.09-0.53). ANP/BNP as suspected causes of salt wasting
      were elevated only in 1/6 and 2/7 patients, respectively. Plasma renin activities
      and aldosterone levels were either suppressed or in the low normal range.
      CONCLUSION: Natriuresis and polyuria are the main diagnostic criteria for CSW.
      The fluid balance in CSW is negative, in contrast to a positive fluid balance in
      SIADH. The length of the disease is self-limited and generally ceases within 2
      weeks, while Na+, K+, and fluid turnover should be monitored carefully. Only a
      minority of our children showed elevated ANP/BNP levels. A dose/effect
      relationship for natriuretic peptide levels and increased Na+ turnover could not
      be established.

PMID- 16607535
TI  - Atlanto-axial rotatory fixation caused by spontaneous intracerebral haemorrhage
      in a child.
AB  - INTRODUCTION: Atlanto-axial rotatory fixation is rare in children and usually
      associated with upper respiratory tract infection or trauma. We present a patient
      who developed the condition acutely as a consequence of rapidly evolving
      hemiplegia secondary to intracerebral haemorrhage. CASE REPORT: A previously well
      12-year-old boy suddenly developed left hemiparesis within 30 min. Soon after, he
      developed painful torticollis. On examination, a dense left hemiplegia was
      associated with left facial and hypoglossal weakness. On computerised tomography
      (CT) scan there was an intracerebral haemorrhage in the deep aspect of the right
      frontal lobe in the corona radiata, with extension in the ventricular system. The
      plain radiographs of the cervical spine, and CT scan later, confirmed the
      presence of C1-C2 rotatory subluxation. The haematoma was aspirated
      stereotactically through a burr hole, and at the same session, the subluxation
      was reduced by manipulation and traction of the cervical spine. The patient was
      treated with a hard collar. The torticollis did not recur. The hemiparesis
      resolved within 6 months. A subsequent magnetic resonance imaging and magnetic
      resonance angiography scan indicated possible arterio-venous malformation (AVM)
      at the site of the haemorrhage, which was confirmed with digital subtraction
      angiography. The AVM was surgically excised 1 year from the original haemorrhage.
      DISCUSSION: In the absence of any other predisposing factor, it is postulated
      that the acute atlanto-axial rotatory subluxation was secondary to the acute loss
      of muscular tone due to the acute hemiparesis. This explains that the subluxation
      has not recurred a year after, while the hemiparesis has completely resolved.

PMID- 16607536
TI  - The efficient isolation of murine splenic dendritic cells and their cytochemical
      features.
AB  - Despite their importance in professional antigen presentation and their
      ubiquitous presence, dendritic cells (DCs) are usually found in such trace
      amounts in tissues that their isolation with high purity is a difficult task.
      Because of their scarcity, accurate determination of the purity of isolated
      dendritic cells is very important. In this study, we purified murine splenic
      dendritic cells by a three-step enrichment method and evaluated their
      morphological, cytochemical and functional characteristics. Purity of the
      isolated cells was determined by established methods such as flow cytometry (FC)
      and immunocytochemistry (ICC) using anti-CD11c monoclonal antibody. In order to
      test purified DC functional properties, we used in vivo antigen presentation
      assay. Our results showed that antigen-pulsed DCs are potent stimulators of
      antigen-specific lymphocyte proliferation. We studied myeloperoxidase (MPO) and
      non-specific esterase (NSE) activity in isolated cells to determine the purity of
      dendritic cells compared to more conventional methods. Our results showed that
      murine splenic dendritic cells were deficient in both MPO and NSE activity and
      the percentage of purity obtained by NSE staining on isolated cells was
      comparable to the results obtained by either FC or ICC. To our knowledge, this is
      the first report on using NSE activity for determination of the purity of
      isolated murine splenic dendritic cells. We, therefore, recommend that NSE
      activity be employed as a simple, inexpensive and yet accurate method for
      evaluation of the purity of isolated murine splenic dendritic cells.

PMID- 16607537
TI  - Nucleolar localization of a reverse transcriptase related to telomere maintenance
      in Chironomus (Diptera).
AB  - A growing number of cellular processes originally thought not to involve the
      nucleolus now seem to be associated with this organelle. In recent years, a
      variety of RNAs and proteins with no apparent function in ribosome genesis have
      been discovered in this nuclear compartment. This paper reports the presence in
      the nucleolus of a reverse transcriptase (RT) previously found to be associated
      with telomeres in Chironomus. Immunofluorescence detection using a specific
      antibody against conserved domains shared by RTs showed a distinct pattern of
      staining in the giant nucleoli of polytenized cells. This nucleolar localization
      was confirmed in a number of larval tissues and embryonic cells of Chironomus
      thummi and C. pallidivitatus; its distribution showed a definite necklace pattern
      that did not completely colocalize with fibrillarin or nucleolin and appeared to
      be different to that of typical nucleolar components. There is evidence that both
      telomerase RT and RNA template subunits are present in the nucleoli of mammalian
      and yeast cells. However, chironomids do not have typical telomeres or
      telomerase. As in other Diptera, telomeres lack the short, simple repeats
      maintained by telomerase and instead have more complex sequences in the range of
      hundreds of nucleotides. It has been suggested that the RT associated with these
      telomeres might be involved in their maintenance, perhaps involving a mechanism
      similar to that of telomerase retrotranscription and retrotransposition in
      Drosophila. The present results indicate that the putative Chironomus telomere
      elongation machinery and telomerase share a nucleolar localization. This
      reinforces the idea that nucleoli are functionally linked to telomere maintenance
      irrespective of the differences in their molecular organization and therefore in
      the strategy adopted for their elongation.

PMID- 16607538
TI  - Binding of galectin-1 (gal-1) to the Thomsen-Friedenreich (TF) antigen on
      trophoblast cells and inhibition of proliferation of trophoblast tumor cells in
      vitro by gal-1 or an anti-TF antibody.
AB  - Galectin-1 (gal-1), a member of the mammalian beta-galactoside-binding proteins,
      recognizes preferentially Galbeta1-4GlcNAc sequences of several cell surface
      oligosaccharides. We demonstrate histochemically that the lectin recognizes
      appropriate glycotopes on the syncytiotrophoblast and extravillous trophoblast
      layer from second trimester human placenta and on BeWo chorion carcinoma cells.
      Gal-1 binding to BeWo cells was diminished by the Thomsen-Friedreich (TF)
      disaccharide (Galbeta1-3GalNAc-) conjugated to polyacrylamide (TF-PAA). Gal-1
      also inhibited BeWo cell proliferation in a concentration-dependent manner.
      Similar antiproliferative effects were also observed with an anti-TF monoclonal
      antibody (mAb, A78-G/A7). Therefore, we conclude that ligation of Galbeta1
      4GlcNAc and Galbeta1-3GalNAc epitopes on BeWo cells may have regulatory effects
      on cell proliferation.

PMID- 16607540
TI  - Human metapneumovirus infections cause similar symptoms and clinical severity as
      respiratory syncytial virus infections.
AB  - Human metapneumovirus (hMPV) is a recently discovered pathogen in respiratory
      tract infection. The published literature suggests milder illness severity in
      hMPV compared with respiratory syncytial virus (RSV) infection. In two
      consecutive seasons, 637 nasopharyngeal aspirates from pediatric patients were
      tested by hMPV polymerase chain reaction, and risk factors and clinical and
      laboratory items were analyzed. The hMPV patients were compared with hMPV
      negative but RSV-positive patients by matched pair analysis. HMPV was detected in
      17.9% of all samples. In total, 88 hMPV-infected patients with complete datasets
      were considered. More than half of all hMPV patients were older than 12 months,
      45.5% had at least one risk factor for a severe course of viral respiratory tract
      infection, and 27.3% were born prematurely, 15.9% with a birth weight <1,500 g.
      At least one other virus was also detected in 39 patients (44.3%; RSV in 29.5%).
      Coinfection did not result in greater severity of illness. On matched pair
      analysis (hMPV-positive/RSV-negative vs. hMPV-negative/RSV-positive), the
      epidemiological and clinical features of hMPV infection were similar to those of
      RSV infection, as in the hMPV group higher proportions of patients with hypoxemia
      on admission (33% vs. 21%) and of intensive care treatment (20.8% vs. 10.4%) were
      observed. More hMPV patients showed lobar infiltrates in radiological chest
      examination. In 60% of all hMPV infections, the attending physicians prescribed
      antimicrobial chemotherapy. We conclude that in hospitalized children, hMPV
      infection is as serious as RSV infection and therefore deserves the same
      attention. Virologic diagnosis from respiratory secretions is mandatory because
      clinical, laboratory, and radiological signs cannot sufficiently discriminate
      between viral and bacterial respiratory tract infection in infants and children.

PMID- 16607541
TI  - Bone microvascular pattern around loaded dental implants in a canine model.
AB  - The vascularity of the implant bed is a very important parameter in both bone
      formation and maintenance after dental implants insertion. The relationship
      between bone and vessels network organization is still unknown. The aim of this
      study was to investigate the three-dimensional bone vascular canals of the peri
      implant bone after loading. A total of ten implants with sandblasted and acid
      etched surface were placed in the mandible of a beagle dog. Three months later,
      the implants were connected and loaded. The dog was killed after 12 months. The
      specimens were embedded and processed for scanning electron microscopy (SEM)
      analysis. After a 1-year loading period, a very intricate vessel network could be
      seen around the implants. The vessels, with neighbouring soft tissues, were round
      in shape and showed a lot of anastomoses with a mesh-like appearance. They ran
      circularly around the dental implant. In the bone, the majority of the vessels
      appeared to ran parallel to the mandibular canal. After a 1-year loading period,
      the peri-implant bone vasculature looked like a mesh that surrounded the
      implants. Nevertheless, the presence of many thick vessels inside the peri
      implant crestal bone indicates a high metabolic need and also a different bone
      organization, as no osteons were noted. The crater-like bone loss around the
      marginal part of the implant could be related to the microvasculature "strain". A
      high strain level could continuously activate the osteocyte-vessel syncytium,
      producing a net bone loss.

PMID- 16607539
TI  - Molecular properties of P2X receptors.
AB  - P2X receptors for adenosine tri-phosphate (ATP) are a distinct family of ligand
      gated cation channels with two transmembrane domains, intracellular amino and
      carboxy termini and a large extracellular ligand binding loop. Seven genes (P2X(1
      7)) have been cloned and the channels form as either homo or heterotrimeric
      channels giving rise to a wide range of phenotypes. This review aims to give an
      account of recent work on the molecular basis of the properties of P2X receptors.
      In particular, to consider emerging information on the assembly of P2X receptor
      subunits, channel regulation and desensitisation, targeting, the molecular basis
      of drug action and the functional contribution of P2X receptors to physiological
      processes.

PMID- 16607542
TI  - Diffusion tensor imaging in polymicrogyria: a report of three cases.
AB  - INTRODUCTION: Polymicrogyria (PMG), a neuronal migration disorder, commonly
      manifests as a seizure disorder. The aim of this study was to look for the
      abnormalities in the underlying white matter using diffusion tensor imaging (DTI)
      that appeared normal on conventional magnetic resonance imaging (MRI) in patients
      with PMG. METHODS: DTI was performed in three patients with PMG and eight age-
      and sex-matched healthy controls. Fractional anisotropy (FA) and mean diffusivity
      (MD) values were calculated for the cortex and adjoining subcortical white matter
      in both controls and patients. RESULTS: We observed a significantly decreased
      mean FA value with no significant change in the MD value in subcortical white
      matter underlying polymicrogyric cortex (FA = 0.23+/-0.04, MD = 1.0+/-0.05 x 10(
      3) mm(2)/s) as compared to both contralateral (FA = 0.32+/-0.04, MD = 1.0+/-0.05
      x 10(-3) mm(2)/s) and normal control (FA = 0.32+/-0.04, MD = 1.0+/-0.06 x 10(-3)
      mm(2)/s) white matter. Significantly increased MD and decreased FA values were
      also observed in the polymicrogyric cortex (FA = 0.08+/-0.01, MD = 1.2+/-0.10 x
      10(-3) mm(2)/s) as compared to normal contralateral (FA = 0.12+/-0.04, MD = 1.1+/
      0.09 x 10(-3) mm(2)/s) and normal control (FA = 0.12+/-0.01, MD = 1.1+/-0.09 x
      10(-3) mm(2)/s) cortex. CONCLUSION: Significantly decreased FA values with no
      change in MD values in the subcortical white matter subjacent to polymicrogyric
      cortex reflect microstructural changes in the white matter probably due to the
      presence of ectopic neurons.

PMID- 16607543
TI  - Improved distal distribution of n-butyl cyanoacrylate glue by simultaneous
      injection of dextrose 5% through the guiding catheter: technical note.
AB  - INTRODUCTION: The use of n-butyl cyanoacrylate (NBCA) as an adhesive agent for
      embolization of high-flow intracranial and extracranial vascular lesions is well
      established. To be successful, the embolization of arteriovenous malformations
      and fistulas must achieve obliteration of the arteriovenous shunts themselves
      rather than simply occlude the feeders proximal to the lesion. However, the
      feeders cannot always be negotiated over their entire length. This is often the
      case with dural arteriovenous fistulas (DAVF), which are usually vascularized by
      long and intricate meningeal networks. In such situations, NBCA may not be able
      to reach the lesion itself, rendering the embolization ineffective. We present a
      new technique that improves distal distribution of NBCA glue. METHODS: The
      technique described in this report consists of injecting dextrose 5% through the
      guiding catheter simultaneously with the superselective injection of NBCA glue
      into the targeted feeding branch. The technique is illustrated with three cases
      of posterior fossa DAVF. RESULTS: In the reported cases, flooding the territory
      of the targeted vessel with non-ionic dextrose 5% allowed deep progression of the
      glue by delaying contact with ionic substances. Excellent distribution of the
      NBCA glue reaching the site of the arteriovenous shunts was thus obtained despite
      suboptimal proximal microcatheter tip positions. CONCLUSION: Simultaneous
      perfusion of dextrose 5% through the guiding catheter during NBCA injection
      dramatically improves the distal progression of glue through small, tortuous
      arterial feeders. This technique has the potential to increase the therapeutic
      value of transarterial embolization for DAVFs.

PMID- 16607544
TI  - Outcome of radioiodine therapy without, on or 3 days off carbimazole: a
      prospective interventional three-group comparison.
AB  - PURPOSE: Carbimazole ameliorates hyperthyroidism but reduces radioiodine uptake
      and adversely affects the outcome of simultaneous radioiodine therapy. We
      explored whether withdrawal of carbimazole for 3 days can restore the outcome of
      radioiodine treatment without concurrent exacerbation of hyperthyroidism. By
      generating three groups with comparable radioiodine uptake, we also investigated
      whether the effect of carbimazole depends on the radioiodine uptake. METHODS:
      Stratified by a radioiodine uptake >30%, 227 consecutive adult patients were
      prospectively assigned to radioiodine therapy (target dose 200 Gy) without, on or
      3 days off carbimazole. Patients were clinically (Crooks-Wayne score) and
      biochemically (T(3), fT(4), TSH) followed up after 3, 6 and 12 months. Primary
      endpoint was outcome 12 months after radioiodine therapy. RESULTS: A total of 207
      patients completed follow-up (toxic nodular goitre, n=117; Graves' disease,
      n=90). The overall success rate was 71.5%. Patients without and 3 days off
      carbimazole had similar biochemical (81.4% and 83.3%, respectively; p=0.82) and
      clinical outcomes [median (range) Crooks-Wayne score 0 (0-16) and 1 (0-10),
      respectively; p=0.73], which were both higher than in patients on carbimazole
      [42.6%, p<0.001; Crooks-Wayne score 3 (0-30), p<0.03]. Time to achieve cure was
      delayed on carbimazole. No changes in thyroid hormone levels occurred after 3
      days' discontinuation of carbimazole. Logistic regression revealed that all
      observed cure rates were independent of entity, sex, age, thyroid volume,
      radioiodine uptake, radioiodine half-life, fT(4), T(3) and TSH. CONCLUSION:
      Patients under carbimazole treatment can be referred for radioiodine therapy
      after withdrawal of carbimazole for only 3 days. Three days of carbimazole
      withdrawal is long enough to restore the success of radioiodine therapy and short
      enough to avoid the risk of exacerbation of hyperthyroidism.

PMID- 16607545
TI  - Malignant mesothelioma of the peritoneum as the cause of a paraneoplastic
      syndrome: detection by 18F-FDG PET.

PMID- 16607548
TI  - Intensive laparoscopic training: the impact of a simplified pelvic-trainer model
      for the urethrovesical anastomosis on the learning curve.
AB  - We prospectively evaluated the learning curve (LC) for laparoscopic
      urethrovesical anastomosis (L-UVA) in an operator-training model and program
      using an innovative simplified pelvic-trainer model. Over a period of 12 months,
      30 LRP were performed by one urologist skilled in open surgery but inexperienced
      in laparoscopy. During the first 15 procedures no systematic training was done.
      Consequentially, a systematic simplified daily program was performed on the
      pelvic trainer with a videolaparoscopic unit. The training lesson consisted of
      intracorporal knotting and suturing, linear and circular interrupted suture
      anastomosis. At the end of each lesson, time and performance error scores were
      recorded and progression curve was plotted for each task. The performances of
      each training tasks were plotted against the performance of L-UVA during the LRP.
      The significance of progression was evaluated using logarithmic regression
      analysis. A steady improvement in time and accuracy of performance skill was
      shown during the first 20 lessons (p<0.001). These improved skill acquisitions
      were proportionally correlated with the time and the accuracy (water-tight) of L
      UVA performance during the last 15 L-RPE. Compared to the first 15 L-RPE, where
      no systematic training was performed, time and accuracy of L-UVA performance in
      the last 15 L-RPE were improved from a mean 51 (median 48, range: 38-75) to 26
      (median 24, range 18-33) min (p<0.001) and from 10 to 15 watertight anastomoses
      (p<0.001), respectively. Using a continuing, systematic, simplified training
      model the LC of L-UVA can be improved significantly in a short time.

PMID- 16607546
TI  - [131I]FIAU labeling of genetically transduced, tumor-reactive lymphocytes: cell
      level dosimetry and dose-dependent toxicity.
AB  - PURPOSE: Donor T cells have been shown to be reactive against and effective in
      adoptive immunotherapy of Epstein-Barr virus (EBV) lymphomas which develop in
      some leukemia patients post marrow transplantation. These T cells may be
      genetically modified by incorporation of a replication-incompetent viral vector
      (NIT) encoding both an inactive mutant nerve growth factor receptor (LNGFR), as
      an immunoselectable surface marker, and a herpes simplex virus thymidine kinase
      (HSV-TK), rendering the cells sensitive to ganciclovir. The current studies are
      based on the selective HSV-TK-catalyzed trapping (phosphorylation) of the
      thymidine analog [(131)I]-2'-fluoro-2'-deoxy-1-beta-D-arabinofuransyl-5-iodo
      uracil (FIAU) as a means of stably labeling such T cells for in vivo trafficking
      (including tumor targeting) studies. Because of the radiosensitivity of
      lymphocytes and the potentially high absorbed dose to the nucleus from
      intracellular (131)I (even at tracer levels), the nucleus absorbed dose (D ( n ))
      and dose-dependent immune functionality were evaluated for NIT(+) T cells labeled
      ex vivo in [(131)I]FIAU-containing medium. METHODS: Based on in vitro kinetic
      studies of [(131)I]FIAU uptake by NIT(+) T cells, D ( n ) was calculated using an
      adaptation of the MIRD formalism and the recently published MIRD cellular S
      factors. Immune cytotoxicity of [(131)I]FIAU-labeled cells was assayed against
      (51)Cr-labeled target cells [B-lymphoblastoid cells (BLCLs)] in a standard 4-h
      release assay. RESULTS AND CONCLUSION: At median nuclear absorbed doses up to 830
      cGy, a (51)Cr-release assay against BLCLs showed no loss of immune cytotoxicity,
      thus demonstrating the functional integrity of genetically transduced, tumor
      reactive T cells labeled at this dose level for in vivo cell trafficking and
      tumor targeting studies.

PMID- 16607549
TI  - Robotic radical prostatectomy: the Vattikuti Urology Institute training
      experience.
AB  - Robotic radical prostatectomy is increasingly becoming a popular surgical
      treatment modality for men with clinically localized prostate cancer.
      Establishing a robotic prostatectomy program is a tremendous undertaking for any
      institution requiring both financial support and a dedicated operating room team.
      A structured approach to learning robotics is paramount in order to successfully
      start a program while optimizing the learning curve to master the technique and
      minimize peri-operative complications. We describe our own experience in
      establishing a robotics program to accomplish a safe and effective operation. In
      addition, we describe the steps utilized in order to teach our structured
      approach to other practitioners and institutions around the world. Robotic
      surgery can be taught to experienced open, as well as, laparoscopic surgeons, and
      incorporated into residency and fellowship training using this structured
      approach to learning.

PMID- 16607550
TI  - Development of robotic program: an Asian experience.
AB  - Robotic surgery was started in the Department of Urology, Hospital Kuala Lumpur,
      in April 2004. We present our experience in developing the program and report the
      results of our first 50 cases of robotic radical prostatectomy. A three-arm da
      Vinci robotic system was installed in our hospital in March 2004. Prior to
      installation, the surgeons underwent training at various centers in the United
      States and Paris. The operating theatre was renovated to house the system.
      Subsequently, the initial few cases were done with the help of proctors. Data
      were prospectively collected on all patients who underwent robot-assisted radical
      prostatectomy for localized carcinoma of the prostate. Fifty patients underwent
      robot assisted radical prostatectomy from March 2004 to June 2005. Their ages
      ranged from 52 to 75 years, (average age 60.2 years). PSA levels ranged from 2.5
      to 35 ng/ml (mean 10.6 ng/ml). Prostate volume ranged from 18 to 130 cc (average
      32.4 cc). Average operating time for the first 20 cases was 4 h and for the next
      30 cases was 2.5 h. Patients were discharged 1-3 days post-operatively. Catheters
      were removed on the fifth day following a cystogram. The positive margin rate as
      defined by the presence of cancer cells at the inked margin was 30%. Twenty-one
      patients had T1c disease and one had T1b on clinical staging. Of these, two were
      apical margin positive. Twenty-six patients had T2 disease and eight of them were
      apical margin positive. Two patients had T3 disease, one of whom was apical
      margin positive. Five patients (10%) had PSA recurrence. Five patients had a
      poorly differentiated carcinoma and the rest had Gleason 6 or 7. Eighty percent
      of the patients were continent on follow-up at 3 months. Of those who were potent
      before the surgery, 50% were potent at 3-6 months. The robotic surgery program
      was successfully implemented at our center on the lines of a structured program,
      developed at Vattikuti Urology Institute (VUI). We succeeded in creating a team
      and safely implemented the robotic program in our system. Adequate funding and
      extensive training followed by a short term proctoring are essential for this
      implementation.

PMID- 16607551
TI  - The 'scrubbed surgeon' in robotic surgery.
AB  - One of the principal reasons for the rapid progress of robotic surgery has been
      its advantage in allowing laparoscopy naive surgeons to offer minimal access
      surgery to their patients. While this may continue to be an advantage of this
      modality, it has to be remembered that this has often been possible primarily due
      to the availability of an assistant who has at least basic laparoscopy skills
      that permit the performance of critical patient side tasks. We review the
      literature on the role of the assistant or the 'scrubbed surgeon' in robotic
      surgery and discuss the advantages of a properly trained assistant in a
      developing and established robotic surgery program.

PMID- 16607552
TI  - Rabbit articular cartilage defects treated by allogenic chondrocyte
      transplantation.
AB  - Articular cartilage defects have a poor capacity for repair. Most of the current
      treatment options result in the formation of fibro-cartilage, which is
      functionally inferior to normal hyaline articular cartilage. We studied the
      effectiveness of allogenic chondrocyte transplantation for focal articular
      cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage
      harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was
      created in the articular cartilage of both knees in other rabbits. The cultured
      allogenic chondrocytes were transplanted into the defect in the right knees and
      closed with a periosteal flap, while the defects in the left knees served as
      controls and were closed with a periosteal flap alone, without chondrocytes.
      Healing of the defects was assessed at 12 weeks by histological studies.
      Allogenic chondrocyte transplantation significantly increased the amount of newly
      formed repair tissue (P=0.04) compared with that found in the control knees. The
      histological quality score of the repair tissue was significantly better
      (P=0.05), with more hyaline characteristics in the knees treated with allogenic
      chondrocytes than in the control knees. Articular cartilage defects treated with
      allogenic chondrocyte transplantation result in better repair tissue formation
      with hyaline characteristics than those in control knees.

PMID- 16607553
TI  - Single incision nailing of the floating knee--do we ignore the knee ligaments?
AB  - The incidence of knee ligament injuries in the floating knee is as high as 53%
      documented in the literature. The single incision technique (antegrade tibial and
      retrograde femoral nailing through a single incision at the knee) although a good
      technique in terms of speed and ease, has its own disadvantages. Repair or
      reconstruction of a torn anterior or posterior cruciate ligament after a single
      incision technique can be a difficult proposition. Antegrade femoral and tibial
      nailing (two incisions) makes treatment of knee ligament injuries easier.

PMID- 16607554
TI  - Role of staged endoprosthetic revision with flap cover for limb salvage in
      endoprosthetic failure.
AB  - Endoprosthetic replacement (EPR) is commonly required for limb salvage in bone
      malignancies. Endoprosthetic failure is a term used to denote mechanical failure
      or infection usually requiring removal of the prosthesis. Treatment of infection
      consists of EPR revision with or without placement of a temporary spacer. Flap
      cover (either local or free) may be required if the overlying soft tissues are of
      concern. It is claimed that the investment of the endoprosthesis in well
      vacularised soft tissue facilitates the eradication of infection. This series
      included nine patients with endoprosthetic failure due to chronic infection who
      needed flap cover. These patients underwent revision of the EPR in two stages.
      The first stage of revision included removal of the endoprosthesis, insertion of
      a spacer and soft tissue reconstruction. If serial sampling of the periprosthetic
      space failed to demonstrate microbial growth, the spacer was exchanged for an
      endoprosthesis. A total of nine patients underwent staged revision of
      endoprosthesis. In five patients cover was provided by a local pedicled flap and
      in four by a free flap. Patients undergoing cover by a broad flat
      musculocutaneous flap (i.e. free/pedicled latissimus dorsi) performed better.
      This study reports the results of attempted limb salvage in endoprosthetic
      failure due to infection in nine cases. Initial findings in this small series
      indicate that staged revision and soft tissue reconstruction in the form of
      muscle flap investment of the endoprosthesis carries a higher rate of successful
      limb salvage.

PMID- 16607555
TI  - Meningiomas infiltrating the superior sagittal sinus: surgical considerations of
      328 cases.
AB  - The aim of the study was to discuss our management strategy and results of
      patients affected by meningiomas infiltrating the superior sagittal sinus. We
      describe 328 patients with meningiomas that were infiltrating the superior
      sagittal sinus. All the patients were surgically treated. Patients with
      meningioma involving the anterior segment of the sinus underwent total sinus
      resection. Patients with meningioma that was infiltrating the middle and
      posterior third of the sinus had a complete sinus removal if the dural sinus was
      completely obliterated by meningioma and incomplete removal if the sinus was not
      occluded. The tumour removal was grade I according to Simpson's grading system in
      193 cases and grade II or III in the remainder. The superior longitudinal sinus
      was totally resected in 215 patients and marginally resected in 113. The tumour
      reappeared in 38 patients. The number of re-interventions did not affect clinical
      outcome. The extent of removal significantly influenced the regrowth or
      recurrence rate. Our results suggest that the risks of aggressive surgery, with
      sinus reconstruction, may be avoided, and conservative surgery for meningiomas
      that are infiltrating but not obliterating the superior sagittal sinus may be a
      reasonable choice.

PMID- 16607556
TI  - Relationship between DNA methylation and histone acetylation levels, cell redox
      and cell differentiation states in sugarbeet lines.
AB  - In order to evaluate the permanent chromatin remodeling in plant allowing their
      high developmental plasticity, three sugarbeet cell lines (Beta vulgaris L.
      altissima) originating from the same mother plant and exhibiting graduate states
      of differentiation were analyzed. Cell differentiation has been estimated by the
      cell redox state characterized by 36 biochemical parameters as reactive oxygen
      species steady-state levels, peroxidation product contents and enzymatic or non
      enzymatic protective systems. Chromatin remodeling has been estimated by the
      measurement of levels of DNA methylation, histone acetylation and corresponding
      enzyme activities that were shown to differ between cell lines. Furthermore,
      distinct loci related to proteins involved in cell cycle, gene expression
      regulation and cell redox state were shown by restriction landmark genome
      scanning or bisulfite sequencing to display differential methylation states in
      relation to the morphogenic capacity of the lines. DNA methylating, demethylating
      and/or histone acetylating treatments allowed to generate a collection of
      sugarbeet cell lines differing by their phenotypes (from organogenic to
      dedifferentiated), methylcytosine percentages (from 15.0 to 43.5%) and acetylated
      histone ratios (from 0.37 to 0.52). Correlations between methylcytosine or
      acetylated histone contents and levels of various parameters (23 or 7,
      respectively, out of 36) of the cell redox state could be established. These data
      lead to the identification of biomarkers of sugarbeet morphogenesis in vitro
      under epigenetic regulation and provide evidence for a connection between plant
      morphogenesis in vitro, cell redox state and epigenetic mechanisms.

PMID- 16607557
TI  - [Acute diagnosis of spinal trauma].
AB  - Most traumatic spinal injuries result from a high-energy process and are
      accompanied by other injuries. Following the CCSPR study, the presence of all low
      risk factors (simple trauma mechanism, fully conscious, ambulatory at any time
      since trauma, neck rotation exceeding 45 degrees bilaterally) obviates the need
      to acutely image the cervical spine. Imaging is indicated in all other patients.
      Emergency spiral CT should be performed as the first imaging method in high-risk
      and moderate-risk patients; only in low-risk patients should conventional
      radiography be performed and trusted as the sole modality. The AO classification
      according to Magerl et al. is used for the subaxial spine, whereas the upper
      cervical spine should be classified separately because the anatomy is different
      at each level. Radiological evaluation of traumatic spinal injuries should be
      done systematically using the "ABCS" scheme.

PMID- 16607558
TI  - At least one YMHCI molecule in the chicken is alloimmunogenic and dynamically
      expressed on spleen cells during development.
AB  - Transcriptionally active, MHC class I (MHCI) loci are located in two separate
      polymorphic genomic regions in the chicken called B and Y. The YMHCI gene
      sequences encode molecules with uncommon substitutions in the antigen-binding
      region indicating that YMHCI molecules are likely unique and may bind a
      specialized form of antigen distinct from that of other antigen-binding MHCI
      molecules. To learn whether YMHCI gene expression results in the production of
      alloantigens at the cell surface, we immunized 15I(5) x 7(2) : chickens using
      syngeneic RP9 cells expressing transduced YF1w*7.1, a potentially alloimmunogenic
      YMHCI allele from the Y7 haplotype present in line C. The resulting antisera show
      that YF1w*7.1 MHCI molecules are immunogenic and expressed on the surfaces of
      cells in blood and spleen of line C chickens. Virtually all CD3+, CD4+, and CD8+
      cells circulating in line C blood are positive, as are BU1+ cells. The YF1w*7.1
      MHCI allele is dynamically expressed at levels comparable to but
      transcriptionally independent of classical BMHCI on erythrocytes, lymphocytes,
      granulocytes, monocytes, and thrombocytes within the spleen pre- and post
      hatching. The antisera react with cells from two among four haplotypes
      segregating in closed populations of lines N and P. YMHCI shares features
      associated with both classical and non-classical MHCI. It is becoming
      increasingly likely that YMHCI has a fundamental role in avian immunity and
      thereby needs to be included in the growing spectrum of functionally active,
      diverse MHCI molecules no longer adequately described by the classical/non
      classical dichotomy.

PMID- 16607559
TI  - Comparison of preparation techniques of mixed samples (fungi-helminth eggs) for
      scanning electron microscopy by critical point drying.
AB  - We compared three preparation techniques for critical point drying of fungus
      Paecilomyces lilacinus (Thom) Samson with Toxocara canis (Werner) Johnston and
      Taenia hydatigena Linneo eggs by scanning electron microscopy. We evaluated
      filtration (first), centrifugation (second), and phytoplankton network (third) in
      critical point drying methods. The first and third methods were advantageous for
      T. canis eggs because they preserved the quantity and quality of samples to
      obtain better images definition. The best technique for T. hydatigena eggs was
      the addition of phytoplankton network in critical point drying which preserved
      these helminth eggs.

PMID- 16607560
TI  - Antihypertensive treatment and endothelium-dependent venodilation in sleep
      disordered breathing.
AB  - Sleep-disordered breathing (SDB) is associated with nitric oxide-mediated
      endothelial dysfunction and increased risk and prevalence of cardiovascular
      disease, namely, arterial hypertension. A substantial number of patients do not
      comply with nasal continuous positive airway pressure (nCPAP) treatment. These
      individuals have a persisting increased cardiovascular risk. Antihypertensive
      drugs have shown to improve nitric oxide-mediated endothelial dysfunction. We
      therefore designed a study to test the hypothesis that antihypertensive drug
      treatment in hypertensive patients with SDB can have beneficial effects on nitric
      oxide-mediated endothelial function in the absence of treatment with nCPAP. Six
      patients with SDB and treated arterial hypertension, six normotensive patients
      with SDB, and six healthy controls received sleep studies and an assessment of
      venodilation using the dorsal hand vein technique. Polygraphic measures using
      standard overnight sleep studies and dose-response curves to the endothelium
      dependent vasodilator bradykinin were obtained. Maximum nitric-oxide-mediated
      dilation to bradykinin was significantly higher in patients with SDB who had
      received antihypertensive drug treatment compared to normotensive SDB patients.
      Nitric oxide-mediated dilation in hypertensive patients with SDB was similar to
      nitric oxide-mediated dilation in healthy controls. After treatment of
      normotensive patients with SDB using nCPAP, nitric oxide-mediated dilation in
      normotensive SDB patients was comparable to nitric oxide-mediated dilation in SDB
      patients with antihypertensive drug treatment and normal controls. Hypertensive
      patients with SDB present a normal nitric oxide-mediated endothelial function
      under antihypertensive treatment.

PMID- 16607561
TI  - Gene amplification, mutation, and protein expression of EGFR and mutations of
      ERBB2 in serous ovarian carcinoma.
AB  - EGFR and erbB-2 are targets for specific cancer therapy. The purpose of this
      study was to examine the frequency and clinicopathological correlations of gene
      amplification, protein expression, and mutations of EGFR and ERBB2 in serous
      carcinoma, the most common and aggressive type of ovarian cancer. Tissue
      microarray constructed of 398 carcinomas was examined by chromogenic in situ
      hybridization (CISH) and by immunohistochemistry. Cases with amplification of
      EGFR by CISH were further analyzed by fluorescence in situ hybridization. One
      hundred ninety-eight samples were analyzed for mutations in exons 18, 19, or 21
      of EGFR and in exon 20 of ERBB2 using denaturating high-performance liquid
      chromatography and direct sequencing. Amplification of EGFR was present in 12%
      (41/333), low-level gain in 43% (144/333), and protein overexpression in 17%
      (66/379) of the tumors. Both increased copy number and overexpression of EGFR
      were associated with high tumor grade, greater patient age, large residual tumor
      size, high proliferation index, aberrant p53, and poor patient outcome.
      Furthermore, increased copy number of EGFR was associated with increased copy
      number of ERBB2. No mutations were identified in EGFR, whereas one tumor had an
      insertion mutation in exon 20 of ERBB2. Both amplification and protein
      overexpression of EGFR occur in serous ovarian carcinoma, but EGFR copy number
      has a stronger prognostic value. This makes EGFR amplification a potentially
      useful criterion for selecting patients in clinical trials testing the effect of
      EGFR inhibitors in serous ovarian carcinoma.

PMID- 16607562
TI  - The GT to GC single nucleotide polymorphism at the beginning of an alternative
      exon 2C of human MTH1 gene confers an amino terminal extension that functions as
      a mitochondrial targeting signal.
AB  - Human MTH1 protein hydrolyzes oxidized purine nucleotides 8-oxo-2'-deoxyguanosine
      triphosphate (8-oxo-dGTP), 2-OH-dATP or their ribo-forms to their monophosphates,
      thus minimizing replicational and transcriptional errors both in the nuclei and
      mitochondria. MTH1 suppresses mitochondrial dysfunction and cell death caused by
      H(2)O(2). Furthermore, MTH1 suppresses the transient increase in 8-oxoguanine in
      mitochondrial DNA in the dopaminergic nerve terminals in mouse striatum after 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration, and it protects the
      nerve terminals. We previously reported that a novel MTH1 allele with a single
      nucleotide polymorphism (SNP) in its exon 2c segment encodes the fourth MTH1
      isoform, namely, MTH1a (p26), in addition to the three known isoforms, MTH1b
      (p22), c (p21), and d (p18). Another SNP located in exon 4 of the MTH1 gene,
      which is closely linked to the SNP in exon 2c, substitutes the Val83 residue in
      MTH1d with Met83. We herein show that all MTH1 isoforms efficiently hydrolyzed 2
      OH-dATP and 8-oxo-dGTP. The amino terminal region of MTH1a functioned as a
      mitochondrial targeting signal when it was expressed in the HeLa cells as a
      fusion protein with enhanced green fluorescent protein. The cellular
      fractionation revealed that MTH1a(Met83) was localized in the mitochondria to the
      same extent as was MTH1d(Val83). However, the mitochondrial translocation of
      MTH1d(Met83) was less efficient than that of MTH1d(Val83).

PMID- 16607563
TI  - Molecular dissection reveals decreased activity and not dominant negative effect
      in human OTX2 mutants.
AB  - The paired-type homeodomain transcription factor Otx2 is essential for forebrain
      and eye development. Severe ocular malformations in humans have recently been
      associated with heterozygous OTX2 mutations. To document the molecular defects in
      human mutants, Otx2 structural characterization was carried out. A collection of
      deletion and point mutants was created to perform transactivation, DNA binding,
      and subcellular localization analyses. Transactivation was ascribed to both N-
      and C-termini of the protein, and DNA binding to the minimal homeodomain, where
      critical amino acid residues were identified. Acute nuclear localization appeared
      controlled by a nuclear localization sequence located within the homeodomain
      which acts in conjunction with a novel nuclear retention domain that we unraveled
      located in the central part of the protein. This region, which is poorly
      conserved among Otx proteins, was also endowed with dominant negative activity
      suggesting that it might confer unique properties to Otx2. Molecular diagnostic
      of human mutant OTX2 proteins discriminates hypomorphic and loss of function
      mutations from other mutations that may not be relevant to ocular pathology.

PMID- 16607564
TI  - High tibial osteotomy with Puddu plate for the treatment of varus gonarthrosis.
AB  - In this study, the results of open-wedge osteotomy with Puddu plate for the
      treatment of varus gonarthrosis have been evaluated prospectively. This study
      assessed 65 knees of 60 patients with varus gonarthrosis who underwent high
      tibial osteotomies. Our study population consisted of 13 male and 47 female
      patients with a mean age of 54 (range 39-76) years. For the clinical evaluation
      of the patients Hospital of Special Surgery (HSS) score, American Knee Society
      and Oxford knee scores, and for the radiological assessment mechanical axis
      deviation (MAD), lateral distal femoral angle (LDFA), medial proximal tibial
      angle (MPTA), femorotibial angle and Insall-Salvati index were basically taken
      into consideration. Our patients were followed up for an average of 34 (range 18
      60) months. In the last assessments of our cases, mean improvements detected in
      HSS scores, Oxford knee scores, knee and functional scores of Knee Society were
      26.72, 19.18, 49.9, and 30 points, respectively. The radiological examinations
      revealed that their mechanical axes on the average passed 5.09 mm laterally
      achieving an average of 6.5 degrees genu valgum, and a mean Insall-Salvati index
      of 1.09. As complications, superficial wound infection in two patients (3%),
      implant infections in one patient (1.5%), deep vein thrombosis in two patients
      (3%), peroperative lateral tibial plateau fracture in one patient (1.5%), and
      postoperative lateral tibial plateau fracture due to a falling down were
      encountered. According to the results obtained, postoperative pain resolves
      promptly and a significant degree of improvement of knee functions of the
      patients are achieved. Therefore, we believe that high tibial osteotomy with a
      Puddu plate is a valuable alternative to total knee arthroplasty in cases with
      varus gonarthrosis. Although early results are satisfactory, long-term follow-up
      studies are required especially in the middle aged and elderly patient
      populations.

PMID- 16607565
TI  - KT-1000 records smaller side-to-side differences than radiostereometric analysis
      before and after an ACL reconstruction.
AB  - The KT-1000 and similar non-invasive arthrometers are used as a complement to
      clinical examination in the diagnosis of anterior cruciate ligament (ACL) rupture
      and during the follow-up after surgery. We compared the two methods, KT-1000 and
      Radiostereometric analysis (RSA), when used to measure anterior-posterior knee
      laxity (A-P laxity) in patients with ACL rupture, before and after the
      reconstruction of this ligament, in a prospective, comparative study. Twenty-two
      consecutive patients (14 men, 8 women) with a median age of 24 years (range 16
      41) were studied. All the patients had a unilateral ACL rupture and an intact
      contralateral knee. The patients were operated on by one experienced surgeon
      using the bone-patellar tendon-bone (BTB) autograft. Preoperatively and 2 years
      after the reconstruction, all the patients were evaluated using KT-1000 and RSA
      measurements of A-P laxity. The side-to-side differences between the injured and
      the intact knees, that is, total A-P laxity for both knees, are presented.
      Preoperatively, the median side-to-side differences using the two methods (KT
      1000/RSA) were 4.0 (0-10)/7.4 mm (2.2-17.4) (P<0.0001). The total A-P laxity on
      the injured side was 11.0 (6.0-18.0)/10.9 mm (6.2-19.6) (n.s), while it was 8.0
      (6.0-10.0)/3.1 mm (0.2-8.6) on the intact side (P<0.0001). A side-to-side
      difference of more than 3.0 mm was defined as the cut-off value for indicating
      ACL rupture. Using the KT-1000, 11 of 22 (50%) patients had a cut-off value above
      3.0 mm, while the corresponding figure for RSA was 21/22 (95%) patients. At the 2
      year follow-up, the median side-to-side differences using the two methods (KT
      1000/RSA) were 0.5 (-1.5 to 4.0)/2.8 mm (-1.8 to 10.7) (P<0.0001). The total A-P
      laxity on the operated side was 9.5 (7.5-14.0)/6.5 mm (2.4-14.1) (P<0.0001). We
      conclude that the KT-1000 recorded significantly smaller side-to-side differences
      than did the RSA, both before and after the reconstruction of the ACL using a BTB
      autograft. Before it was mainly an effect of larger A-P laxity recordings with KT
      1000 on the intact side, and after the reconstruction, the KT-1000 still recorded
      larger A-P laxity on the intact side and also larger A-P laxity on the
      reconstructed side than RSA.

PMID- 16607566
TI  - Seasonal changes in needle water content and needle ABA concentration of Japanese
      red pine, Pinus densiflora, in declining forests on Mt. Gokurakuji, Hiroshima
      prefecture, Japan.
AB  - To evaluate the effects of air pollution on the decline of Pinus densiflora
      forests, various research has been conducted around Mt. Gokurakuji (34 degrees
      23'N, 132 degrees 19'E, 693 m a.s.l.) north of the Seto Inland Sea, west Japan.
      To investigate the mechanisms responsible for decreases in photosynthesis (Pn)
      and stomatal conductance (gl), delta13C of needles and seasonal changes in the
      water content (WC) and abscisic acid concentration (ABA) of needles were measured
      in various stands. The delta13C values were less negative in declining stands and
      younger needles. ABA and WC were not correlated with each other. WC decreased
      consistently with needle age while the ABA showed a minimum in August and a
      smaller content in older needles. Monthly precipitation and the daily maximum
      vapor pressure were not correlated with ABA and WC. In declining stands, WC and
      ABA tended to be higher and lower, respectively, than in nondeclining stands.
      These results suggest that the trees in declining stands received less water
      stress than those in nondeclining stands and the differences in gl and delta13C
      are not caused by the difference in water stress. The possibilities of the
      effects of air pollution and the infection of pine-wood nematode on the
      physiological decline on the pine needles are discussed.

PMID- 16607567
TI  - Concentrations of inorganic elements in 20 municipal waters in Sweden before and
      after treatment--links to human health.
AB  - The water chemistry of 20 municipal water treatment plants in southern Sweden,
      representing various bedrock situations, and water qualities, were investigated.
      Four water samples, raw and treated, were collected from each plant and analyzed
      by predominantly ICP-OES and ICP-MS at four occasions from June to December,
      2001. The concentrations of Ca, Mg, K, Na, HCO(3) and a number of micronutrients,
      varied considerably in treated waters from the studied plants (ranges; Ca: 9.1
      53.7 mg L(-1), Mg: 1.4-10.9 mg L(-1), K: 1.1-4.8 mg L(-1), Na; 5.4-75.6 mg L(-1),
      HCO(3): 27-217 mg L(-1)). The elimination of Fe and Mn from raw water was
      efficient in all treatments investigated, giving concentrations in treated waters
      below the detection limits at some plants. Softening filters gave waters with Ca
      concentrations comparable to the softest waters in this study. Adjustment of pH
      by use of chemicals like lye, soda or lime, modified the consumer water
      composition significantly, besides raising the pH. It was estimated that drinking
      water contributed to approximately 2.2-13% of the daily Ca uptake, if the
      gastrointestinal uptake efficiency from food and water was estimated to be around
      50%. The corresponding figures for Mg was 1.0-7% and for F 0-59%. None of the
      studied elements showed any significant time trends in raw or treated waters
      during the follow-up period. The concentrations of potentially toxic metals such
      as Al, Pb and U were low and did not indicate risks for adverse health effects
      (ranges; Al: 0.5-2.3 microg L(-1), Pb: 0-0.3 microg L(-1), U: 0.2.5 microg L(
      1)).

PMID- 16607568
TI  - Effect of natural organic matter on arsenic release from soils and sediments into
      groundwater.
AB  - Arsenic (As) contamination in groundwater has received significant attention
      recently. Natural and anthropogenic sources contribute to the worldwide
      occurrence of As contamination. As speciation is an important factor related to
      its toxic and mobile behavior. The release of As from soils and sediments into
      groundwater is governed by several geophysicochemical processes, of which, As
      sorption behavior is of principle significance. This review paper summarizes
      existing information regarding the effects of natural organic matter (NOM) on the
      fate and mobility of As species in the environment. NOM may enhance the release
      of As from soils and sediments into the soil solution, thereby facilitating As
      leaching into the groundwater. The main influencing mechanisms include
      competition for available adsorption sites, formation of aqueous complexes,
      and/or changes in the redox potential of site surfaces and As redox speciation.
      NOM may also serve as binding agents, thereby reducing As mobility. However,
      comparably little research has been performed on this aspect. Since most
      investigations have been done on purified minerals under laboratory conditions,
      further research involving various geological materials under natural
      environmental conditions is required. Development of proper geochemical
      conceptual models may provide means of predicting the role of NOM in arsenic
      leaching and/or immobilization.

PMID- 16607569
TI  - Protein kinase C and downstream signaling pathways in a three-dimensional model
      of phorbol ester-induced angiogenesis.
AB  - Angiogenesis, a critical process in both health and disease, is mediated by a
      number of signaling pathways. Although proangiogenic stimuli, including vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and the
      phorbol ester phorbol-12 myristate-13 acetate (PMA) are known to promote blood
      vessel formation, their downstream targets are ill defined. We sought to
      investigate the signaling pathways required for vessel assembly by utilizing a
      three-dimensional collagen matrix in which human umbilical vein endothelial cells
      (HUVECs) form tubular structures. Our data show that PMA is sufficient for the
      induction of angiogenesis, and that protein kinase C (PKC) is necessary for this
      process. Evaluation of PKC isoforms alpha and sigma revealed that these proteins
      are uniquely regulated. Characterization of an additional PMA target, protein
      kinase D (PKD) demonstrated that this enzyme becomes phosphorylated in HUVECs,
      and may therefore be involved in proangiogenic signaling. Further examination of
      downstream effectors of PKC showed that extracellular signal-regulated kinase
      (ERK) is critical for angiogenesis, and is accordingly phosphorylated in response
      to PMA. Surprisingly however, phosphorylation of ERK is independent of PKC
      activity. In addition, we show that the PKC target sphingosine kinase (SPK) is
      required for vessel formation. These findings illustrate the complexities of
      blood vessel formation, and suggest that activators utilize multiple independent
      pathways to invoke a complete angiogenic response.

PMID- 16607570
TI  - Modelling of carbohydrate-aromatic interactions: ab initio energetics and force
      field performance.
AB  - Aromatic amino acid residues are often present in carbohydrate-binding sites of
      proteins. These binding sites are characterized by a placement of a carbohydrate
      moiety in a stacking orientation to an aromatic ring. This arrangement is an
      example of CH/pi interactions. Ab initio interaction energies for 20 carbohydrate
      aromatic complexes taken from 6 selected ultra-high resolution X-ray structures
      of glycosidases and carbohydrate-binding proteins were calculated. All
      interaction energies of a pyranose moiety with a side chain of an aromatic
      residue were calculated as attractive with interaction energy ranging from -2.8
      to -12.3 kcal/mol as calculated at the MP2/6-311+G(d) level. Strong attractive
      interactions were observed for a wide range of orientations of carbohydrate and
      aromatic ring as present in selected X-ray structures. The most attractive
      interaction was associated with apparent combination of CH/pi interactions and
      classical H-bonds. The failure of Hartree-Fock method (interaction energies from
      +1.0 to -6.9 kcal/mol) can be explained by a dispersion nature of a majority of
      the studied complexes. We also present a comparison of interaction energies
      calculated at the MP2 level with those calculated using molecular mechanics force
      fields (OPLS, GROMOS, CSFF/CHARMM, CHEAT/CHARMM, Glycam/AMBER, MM2 and MM3). For
      a majority of force fields there was a strong correlation with MP2 values. RMSD
      between MP2 and force field values were 1.0 for CSFF/CHARMM, 1.2 for
      Glycam/AMBER, 1.2 for GROMOS, 1.3 for MM3, 1.4 for MM2, 1.5 for OPLS and to 2.3
      for CHEAT/CHARMM (in kcal/mol). These results show that molecular mechanics
      approximates interaction energies very well and support an application of
      molecular mechanics methods in the area of glycochemistry and glycobiology.

PMID- 16607571
TI  - Protein farnesyltransferase: flexible docking studies on inhibitors using
      computational modeling.
AB  - Using MacroModel, peptide, peptidomimetic and non-peptidomimetic inhibitors of
      the zinc metalloenzyme, farnesyltransferase (FTase), were docked into the enzyme
      binding site. Inhibitor flexibility, farnesyl pyrophosphate substrate
      flexibility, and partial protein flexibility were taken into account in these
      docking studies. In addition to CVFM and CVIM, as well as our own inhibitors FTI
      276 and FTI-2148, we have docked other farnesyltransferase inhibitors (FTIs)
      including Zarnestra, which presently is in advanced clinical trials. The AMBER*
      force field was employed, augmented with parameters that were derived for zinc. A
      single binding site model that was derived from the crystal structure of CVFM
      complexed with farnesyltransferase and farnesylpyrophosphate was used for these
      studies. The docking results using the lowest energy structure from the
      simulation, or one of the lowest energy structures, were generally in excellent
      agreement with the X-ray structures. One of the most important findings of this
      study is that numerous alternative conformations for the methionine side chain
      can be accommodated by the enzyme suggesting that the methionine pocket can
      tolerate groups larger than methionine at the C-terminus of the tetrapeptide and
      suggesting alternative locations for the placement of side chains that may
      improve potency.

PMID- 16607572
TI  - Novel approach to evolutionary neural network based descriptor selection and QSAR
      model development.
AB  - Capability of evolutionary neural network (ENN) based QSAR approach to direct the
      descriptor selection process towards stable descriptor subset (DS) composition
      characterized by acceptable generalization, as well as the influence of
      description stability on QSAR model interpretation have been examined. In order
      to analyze the DS stability and QSAR model generalization properties multiple
      random dataset partitions into training and test set were made. Acceptability
      criteria proposed by Golbraikh et al. [J. Comput.-Aided Mol. Des., 17 (2003) 241]
      have been chosen for selection of highly predictive QSAR models from a set of all
      models produced by ENN for each dataset splitting. All QSAR models that pass
      Golbraikh's filter generated by ENN for each dataset partition were collected.
      Two final DS forming principles were compared. Standard principle is based on
      selection of descriptors characterized by highest frequencies among all
      descriptors that appear in the pool [J. Chem. Inf. Comput. Sci., 43 (2003) 949].
      Search across the model pool for DS that are stable against multiple dataset
      subsampling i.e. universal DS solutions is the basis of novel approach. Based on
      described principles benzodiazepine QSAR has been proposed and evaluated against
      results reported by others in terms of final DS composition and model predictive
      performance.

PMID- 16607574
TI  - The nature and impact of conflict within service coordination teams for children
      and adolescents with serious emotional and behavioral challenges.
AB  - While both theory and empirical research regarding work team performance suggests
      that conflict can play an important role in determining productivity and other
      outcomes, the impact of conflict on the effectiveness of service coordination
      teams is not well understood. In this study, the team records and charts of 189
      young people maintained by service coordinators in a system of care initiative
      were analyzed to identify the number of intra-team conflicts, the participants
      involved in each conflict, the theme of each conflict and their relationship with
      the likelihood that young people were successful in meeting their treatment
      goals. Findings indicate that interpersonal concerns and concerns about team
      member follow-through were the most frequent types of conflict. More important,
      our analyses suggest that more frequent conflicts significantly increased the
      likelihood that a child and family team (CFT) was unsuccessful in helping the
      youth and family achieve the desired treatment goals. The results underline the
      need for further research on how structure and functioning of services
      coordination teams impact youth and family outcomes.

PMID- 16607575
TI  - Outcomes for rural Medicaid clients with severe mental illness in fee for service
      versus managed care.
AB  - This study compared outcomes for rural Medicaid clients with severe mental
      illness in fee for service versus managed care programs. Interviews were
      conducted with 305 Medicaid clients in rural Oregon (166 in fee for service and
      139 in managed care). Logistic and multivariate regression analyses were used to
      examine client satisfaction, safety, symptoms, functioning, and family
      satisfaction in the fee for service versus managed care groups. There was no
      evidence that conversion of the Medicaid mental health system from fee for
      service to managed care led to changes in outcomes for rural clients with severe
      mental illness.

PMID- 16607576
TI  - [Abdominal involvement in hereditary hemorrhagic teleangiectasia].

PMID- 16607586
TI  - [Significance of radiology for occupational and environmental lung diseases].

PMID- 16607587
TI  - [Staging of prostate cancer: value of the combined information of endorectal MRI,
      biopsy Gleason score, and preoperative PSA level].
AB  - PURPOSE: To evaluate the predictive value of MR imaging criteria, the biopsy
      Gleason score, and preoperative PSA levels for differentiating between T2 and T3
      prostate carcinomas. MATERIALS AND METHODS: Endorectal MR images of 81 patients
      (median age: 65 years, range: 48 to 81 years) who had biopsy-proven prostate
      cancer and underwent a radical prostatectomy were analyzed retrospectively. The
      existence of different imaging features were recorded for each patient. A
      radiological analysis comprising all used imaging criteria was also performed for
      every patient. Optimal cut-off levels for the biopsy Gleason score and
      preoperative PSA levels were obtained using ROC analyses. Subsequently, a
      logistic regression analysis was performed to identify features which make a
      significant contribution to the prediction of the tumor stage. RESULTS:
      Histological examination showed that 24 patients (29.6 %) had a T3 tumor and 57
      patients (70.4 %) had a T2 tumor. The mean preoperative PSA level was 9.4 ng/ml
      (+/- 7 ng/ml), and the median Gleason score was 6 with a range of 4 to 8. The
      radiological judgment comprising all imaging criteria led to a sensitivity of
      54.2 % and specificity of 79 % for the detection of a T3 tumor. The obliteration
      of the rectoprostatic angle (regression coefficient B = 2.30; standard error (se)
      = 0.80; p = 0.002) and the biopsy Gleason score (B = 1.16; se = 0.3; p = 0.001)
      were the parameters with the highest independent predictive value for the
      diagnosis of an extracapsular tumor spread. The other radiological criteria and
      the preoperative PSA level were not statistically significant. A combination of
      the parameters "obliteration of the rectoprostatic angle" and "biopsy Gleason
      score" led to a sensitivity and specificity of 75 % and 79 %, respectively
      (existence of one parameter sufficient). The optimal cut-off value was a Gleason
      score of 7 for the differentiation between T2 and T3 prostate carcinomas.
      CONCLUSION: In our study, only the criteria "obliteration of the rectoprostatic
      angle" and "biopsy Gleason score" were of predictive value for the diagnosis of a
      T3 prostate carcinoma. The other MR imaging criteria and the preoperative PSA
      levels had no additional benefit.

PMID- 16607588
TI  - [Impact of a PACS/RIS-integrated speech recognition system on radiology reporting
      time and report availability].
AB  - PURPOSE: Quantification of the impact of a PACS/RIS-integrated speech recognition
      system (SRS) on the time expenditure for radiology reporting and on hospital-wide
      report availability (RA) in a university institution. MATERIAL AND METHODS: In a
      prospective pilot study, the following parameters were assessed for 669
      radiographic examinations (CR): 1. time requirement per report dictation (TED:
      dictation time (s)/number of images [examination] x number of words [report])
      with either a combination of PACS/tape-based dictation (TD: analog dictation
      device/mini-cassette/transcription) or PACS/RIS/speech recognition system (RR:
      remote recognition/transcription and OR: online recognition/self-correction by
      radiologist), respectively, and 2. the Report Turnaround Time (RTT) as the time
      interval from the entry of the first image into the PACS to the available RIS/HIS
      report. Two equal time periods were chosen retrospectively from the RIS database:
      11/2002 - 2/2003 (only TD) and 11/2003 - 2/2004 (only RR or OR with speech
      recognition system [SRS]). The mid-term (> or = 24 h, 24 h intervals) and short
      term (< 24 h, 1 h intervals) RA after examination completion were calculated for
      all modalities and for CR, CT, MR and XA/DS separately. The relative increase in
      the mid-term RA (RIMRA: related to total number of examinations in each time
      period) and increase in the short-term RA (ISRA: ratio of available reports
      during the 1st to 24th hour) were calculated. RESULTS: Prospectively, there was a
      significant difference between TD/RR/OR (n = 151/257/261) regarding mean TED
      (0.44/0.54/0.62 s [per word and image]) and mean RTT (10.47/6.65/1.27 h),
      respectively. Retrospectively, 37 898/39 680 reports were computed from the RIS
      database for the time periods of 11/2002 - 2/2003 and 11/2003 - 2/2004. For CR/CT
      there was a shift of the short-term RA to the first 6 hours after examination
      completion (mean cumulative RA 20 % higher) with a more than three-fold increase
      in the total number of available reports within 24 hours (all modalities). The
      RIMRA for CR/CT/MR was 3.1/5.8/4.0 in the first 24 hours, and 2.0 for XA/DS in
      the second 24-hour interval. CONCLUSION: In comparison to tape-based dictation,
      an SRS results in a significantly higher primary time expenditure and a modified
      report dictation workflow. In a university institution, a PACS/RIS-integrated SRS
      achieves a marked improvement in both short- and mid-term RA which eventually
      results in an improvement in patient care.

PMID- 16607589
TI  - [Initial results of shoulder MRI in external rotation after primary shoulder
      dislocation and after immobilization in external rotation].
AB  - PURPOSE: A change in the strategy for treating primary anterior traumatic
      dislocation of the shoulder has occurred. To date, brief fixation of internal
      rotation via a Gilchrist bandage has been used. Depending on the patient's age, a
      redislocation is seen in up to 90 % of cases. This is due to healing of the
      internally rotated labrum-ligament tear in an incorrect position. In the case of
      external rotation of the humerus, better repositioning of the labrum ligament
      complex is achieved. Using MRI of the shoulder in external rotation, the extent
      of the improved labrum-ligament adjustment can be documented, and the indication
      of immobilization of the shoulder in external rotation can be derived. The aim of
      this investigation is to describe the degree of position changing of the labrum
      ligament tear in internal und external rotation. MATERIALS AND METHODS: 10
      patients (9 male, 1 female, mean age 30.4 years, range 15 - 43 years) with a
      primary anterior dislocation of the shoulder without hyper laxity of the contra
      lateral side and labrum-ligament lesion substantiated by MRI were investigated
      using a standard shoulder MRI protocol (PD-TSE axial fs, PD-TSE coronar fs, T2
      TSE sagittal, T1-TSE coronar) by an axial PD-TSE sequence in internal and
      external rotation. The dislocation and separation of the anterior labrum-ligament
      complex were measured. The shoulders were immobilized in 10 degrees external
      rotation for 3 weeks. After 6 weeks a shoulder MRI in internal rotation was
      performed. RESULTS: In all patients there was a significantly better position of
      the labrum-ligament complex of the inferior rim in external rotation, because of
      the tension of the ventral capsule and the subscapular muscle. In the initial
      investigation, the separation of the labrum-ligament complex in internal rotation
      was 0.44 +/- 0.27 mm and the dislocation was 0.45 +/- 0.33 mm. In external
      rotation the separation was 0.01 +/- 0.19 mm and the dislocation was - 0.08 +/-
      0.28 mm. After 6 weeks of immobilization in 10 degrees external rotation, the
      separation of the labrum was - 0.10 +/- 0.14 mm and the dislocation was - 0.23 +/
      0.21 mm. CONCLUSION: In anterior labrum-ligament tears, the axial MRI of the
      shoulder in external rotation demonstrates a more physiologic position of the
      glenoid. This may indicate an immobilization of the shoulder in external
      rotation, which results in a more anatomical healing of the glenoidal tear. Thus,
      in the case of labrum-ligament tears, MRI in external rotation is becoming
      indispensable.

PMID- 16607590
TI  - [Dose-reduced 16-slice multidetector-row spiral computed tomography in children
      with bronchoscopically suspected vascular tracheal stenosis -- initial results].
AB  - PURPOSE: To evaluate the diagnostic accuracy of contrast-enhanced dose-reduced 16
      slice multidetector-row CT (MDCT) in newborns and infants with fiberoptic
      bronchoscopically suspected vascular-induced tracheal stenosis. MATERIALS AND
      METHODS: 12 children (4 days to 3 years, 1.2 - 13.5 kg body weight) were examined
      using i. v. contrast-enhanced 16-slice MDCT (SOMATOM Sensation 16, Forchheim,
      Germany) without breath-hold and under sedation (11/12). All MDCTs were performed
      with a dose reduction. The beam collimation was 16 x 0.75 mm, except in the case
      of one child. MPRs along the tracheal axis in the x-, y- and z-directions and
      volume-rendering-reconstructions (VRTs) were calculated based on a secondary raw
      data set in addition to conventional axial slices. 2 radiologists used a three
      point grade scale to evaluate the image quality, motion, and contrast media
      artifacts as well as the usefulness of the 2D- and 3D-reconstructions for
      determining the diagnosis. Statistical analysis was performed on the basis of a
      Kappa test. RESULTS: In all cases the cause of the fiberoptic bronchoscopically
      suspected tracheal stenosis was revealed: compression due to the brachiocephalic
      trunk (n = 7), double aortic arch (n = 2), lusorian artery (n = 1), vascular
      compression of the left main bronchus (n = 2). In 3 patients further thoracic
      anomalies, such as tracheobronchial (n = 2), and vascular (n = 2) and vertebral
      (n = 1) anomalies were found. The attenuation in the anomalous vessels was 307 +/
      140 HU. The image noise was 9.8 +/- 1.9 HU. The mean dose reduction was 82.7 +/-
      3.2 % compared to a standard adult thoracic CT. All examinations were rated as
      diagnostically good (median 1, range 1, k = 1). 3D images did not show any stair
      artifacts (median 2, range 1 - 2, k = 1). The image noise was minor to moderate
      and hardly any motion artifacts were seen (median 1, range 1 - 2, k = 0.8).
      Contrast media artifacts were rated zero to minor (median 1.5, range 1 - 2, k =
      0.676). MPRs (median 1, range 1, k = 1) and VRTs (median 1, range 1, k = 1) were
      found to be useful for diagnosis. Subsequent vascular surgery was performed on 8
      patients. CONCLUSION: Contrast-enhanced dose-reduced 16-slice MDCT is effective
      for demonstrating the cause of fiberoptic bronchoscopically suspected vascular
      induced tracheal stenosis even in very small and severely ill children despite
      the small contrast media amount and free breathing.

PMID- 16607591
TI  - [Congenital cystic lung malformations].
AB  - PURPOSE: The aim of the study concerning congenital cystic lung malformations was
      to evaluate prenatal diagnoses postnatally to determine prognostic factors as
      well as to define optimized perinatal management. MATERIALS AND METHODS: The
      study is based on 45 prenatal ultrasound examinations depicting fetal cystic lung
      lesions. 32 of the mothers had follow-up examinations. 5 pregnancies were
      terminated due to CCAM and additional malformations. Complete regression of the
      lesions was seen prenatally in 8 cases and postnatally in 5 children. RESULTS:
      Surgical intervention due to respiratory insufficiency was necessary in 4
      neonates. According to the imaging results, CCAM was present in 4 cases and
      sequestration in 7 patients. No correlation between the imaging findings and the
      surgical results was found in 3 children: One child suffered from rhadomyoid
      dysplasia, and in the case of the second child, a left-sided hernia of the
      diaphragm and additional sequestration were detected. The third child showed AV
      malformation. The cystic lesions of the 14 children operated upon were proven
      histologically. The degree of accuracy in the present study was high. CONCLUSION:
      Precise perinatal management is warranted in order to determine according to the
      clinical relevance surgical intervention and to prevent complications after the
      first year of life. This is performed during the neonatal period for respiratory
      insufficient neonates and within the first year of life for clinically stable
      children.

PMID- 16607592
TI  - [Transhepatic establishment of a port catheter system].

PMID- 16607598
TI  - [The devil takes the hindmost].

PMID- 16607599
TI  - [Heterogeneity of costs of diabetic patients: the Cost of Diabetes Mellitus
      Study].
AB  - BACKGROUND AND OBJECTIVE: Health economic studies in patients with diabetes
      mellitus have demonstrated that a large proportion of the excess cost is caused
      by the treatment of specific complications. It was the aim of this study to
      analyse the distribution of per capita cost of a large cohort of diabetic
      patients in order to develop new strategies for a better identification and care
      of high-risk patients. METHODS: The analysis was based on anonymous data on
      patients with diabetes and an age-matched control group from a large cohort of
      subjects insured by a large statutory health insurance fund (AOK Hesse)
      (n=305736). Costs were fully assessed and related to the state of complications
      and other criteria. RESULTS: The average cost was 5262 euros per diabetic patient
      and year. Excess costs due to the diabetes were estimated at 2507 euros. Costs
      were unevenly distributed, depending on the presence of complications. The
      average excess cost of patients with at least one complication was i 3730 euros
      (469 for patients without complication). In particular, patients on hemodialysis,
      after kidney transplantation or with lower leg amputation, stroke or with
      gangrene or foot ulcer incurred great costs. 5.3% of all diabetic patients
      incurred costs of > or = 20000 euros per year, totalling up to 33.6% of all costs
      of diabetic patients. Another 9.5% of patients incurred costs of between 10000
      euros and 20000 euros per year. Both groups were responsible for 59.6% of total
      costs. In contrast, 55% of the patients incurred costs of < 2500 euros per year,
      amounting to 11.8% of all costs. CONCLUSIONS: There is a considerable variation
      of cost incurred in the management of diabetic patients, as demonstrated in a
      large population-based cohort of diabetics. This increased cost was largely due
      to the presence of complications. High-risk patients should be identified as
      early as possible so that they can receive intensive care to avoid the expensive
      complications of the disease.

PMID- 16607600
TI  - [Rare cause of chronic recurrent pulmonary emboli and pulmonary artery
      hypertension].
AB  - HISTORY AND CLINICAL FINDINGS: A 41-year-old man with known Klippel-Trenaunay
      syndrome was admitted to hospital because of progressive dyspnea on exertion.
      Examination on admission revealed the typical signs of Klippel-Trenaunay
      syndrome, predominantly of the left leg. INVESTIGATIONS: D-dimers were
      significantly increased. Contrast-enhanced computed tomography of the chest
      revealed multiple small pulmonary arterial emboli in subsegmental arteries on
      both lungs. Pulmonary arterial digital subtraction angiography revealed extensive
      peripherally localized perfusion defects. Pulmonary artery pressure measurement
      demonstrated bilateral pulmonary artery hypertension. Phlebography of the left
      lower leg showed marked varices in the calf. There was also a persisting sciatic
      vein. DIAGNOSIS, TREATMENT AND COURSE: The recurrent peripheral pulmonary emboli
      with pulmonary arterial hypertension was a complication of a Klippel-Trenaunay
      syndrome. Another rare entity of this syndrome was a persisting sciatic vein.
      Heparinization was initiated, followed by oral anticoagulation. As the patient
      had not been anticoagulated before, implantation of an inferior vena cava filter
      was not deemed appropriate. CONCLUSIONS: Recurrent peripheral pulmonary emboli
      leading to chronic pulmonary artery hypertension is a rare but typical
      complication of Klippel-Trenaunay syndrome. Early recognition of this syndrome
      and any complications as a separate entity, as well as initiation of therapeutic
      measures, like anticoagulation or early pulmonary thrombendarterectomy for
      chronic pulmonary artery emboli, are of prognostic importance.

PMID- 16607602
TI  - [Pathophysiology of the renin-angiotensin-system in atrial fibrillation].
AB  - Cardiovascular diseases which are associated with an activation of the renin
      angiotensin-system -- myocardial infarction, heart failure, hypertension -- often
      induce atrial fibrillation. The initiation and maintenance of atrial fibrillation
      is not only initiated by mechanical distension of the atria, but also by
      increased atrial expression of components of the renin-angiotensin-system, which
      initiate an inflammatory signal cascade and oxidative stress and in consequence
      myolysis and interstitial fibrosis. Ultimately, locally decreased conduction
      velocity and abbreviated refractory period facilitate reentry circuit(s) as an
      underlying pathomechanism of atrial fibrillation. In a meta-analysis, ACE
      inhibitors and AT (1) blockers, both reduce the relative risk of atrial
      fibrillation by about 30 %. Further prospective randomized clinical studies are
      required to establish final evidence.

PMID- 16607603
TI  - [CranioNet -- an interdisciplinary strategy for craniopharyngioma].
AB  - In patients with craniopharyngioma, pituitary failure and often lifelong hormone
      replacement therapy, persisting ophthalmological problems with impaired vision,
      cranial nerve palsies, and psychoneurological deficits will lead to a persisting
      impairment in quality of life and social competence. Some patients completely
      depend on assistance. To prevent this, a major goal is an early diagnosis and
      limitation of operative radicality to minimize postoperative complications.
      Surgery in centers with special expertise is mandatory. Radiotherapeutical
      strategies are relatively safe and improve the outcome and recurrence-free
      survival after incomplete surgical resection or after local recurrence.
      Multidisciplinary concepts and prospective data acquisition are desirable with
      regard to therapy and outcome in patients with craniopharyngioma. Problems in the
      follow-up period are the development of atherosclerotic complications and
      metabolic syndrome as a consequence of occasionally excessive obesity, which may
      impair the long-term survival of the patients. Cause and progression of these
      complications are not fully understood, therapeutical strategies for the morbid
      obesity are not available. Only interdisciplinary co-operation will help to
      develop and evaluate therapeutical concepts for the management of this rare
      disease.

PMID- 16607604
TI  - [2-Methoxyestradiol -- a new compound for cancer treatment].
AB  - 2-Methoxyestradiol (2-ME2), a physiological metabolite of estrogen, inhibits the
      growth of different tumor types. Many mechanisms of action have been described.
      In addition to a strong antiangiogenic effect and induction of apoptosis, there
      are other important mechanisms, such as the inhibition of microtubules during
      mitosis or the inhibition of the hypoxia-inducible-factor 1alpha (HIF1 alpha).
      Multidrug-resistant cancer cells appear to be highly sensitive to 2-ME2. Studies
      with high dosage 2-ME2 have shown that there are only minimal reversible side
      effects on normal tissue. The experimental data on human tumors have led to the
      initiation of several clinical trials with promising results. We here summarize
      the effect of 2-ME2 on various tumor types in vitro and in vivo, as well as the
      initial results of current clinical trials.

PMID- 16607605
TI  - [Instant dismissal of a physician's assistant. Decision of the District Labor
      Court Dusseldorf on November 4, 2005].

PMID- 16607606
TI  - Cationic amylopectin derivatives as additives for analysis of proteins in
      capillary electrophoresis.
AB  - Positively charged amylopectin, which is a major constituent of cationic starch,
      was used to modify the inner surface of fused-silica capillaries by addition to
      the running solution, which was subsequently employed in CE. Capillaries filled
      with cationic amylopectin derivatives were shown to generate a stable reversed
      EOF in the investigated range of pH 4-8. Among the additives studied, quaternary
      ammonium amylopectin derivatives with high amino and low hydroxypropyl groups
      showed fast electroosmotic mobility and very effectively suppressed the
      adsorption of proteins. The run-to-run and batch-to-batch repeatability of the
      procedures were satisfactory with RSDs of 0.5% and 2.4%, respectively. A basic
      protein, alpha-chymotrypsinogen, migrated within 6 min and the theoretical plate
      number of it reached 560 000 plates/m.

PMID- 16607607
TI  - Selectivity of single, mixed, and modified pseudostationary phases in
      electrokinetic chromatography.
AB  - The selectivity of a compilation of single, mixed, and modified EKC
      pseudostationary phases, described in the literature and characterized through
      the solvation parameter model, is analyzed. Not only have micellar systems of
      different nature been included but also microemulsions, polymeric, and liposomial
      phases. In order to compare the systems, a principal component analysis of the
      coefficients of the solvation equation is performed. From this analysis, direct
      information of the system properties, differences in selectivity, as well as
      evidence of lack of accuracy in some system characterizations are obtained. These
      results become a very useful tool to perform separations with mixtures of
      surfactants, since it is possible to know which mixtures will provide a greater
      selectivity variation by changing only the composition of the pseudostationary
      phases. Furthermore, the variation of the selectivity of some mixtures, as well
      as the effect of the addition of organic solvents on selectivity, is also
      discussed.

PMID- 16607609
TI  - Time-based analysis of silver-stained proteins in acrylamide gels.
AB  - Silver staining of proteins after PAGE often remains the method of choice in many
      laboratories. Nevertheless, it is known that quantification of protein levels is
      keenly restricted to a small range of protein concentrations leading to an over-
      or underestimation of protein amounts. To overcome this, a time-based analysis
      method was developed to avoid the saturation effect of the silver-staining
      reaction, thus resulting in an improved dynamic range of the gel image produced
      and therefore better quantification of proteins. Instead of the well-known end
      point image analysis, gray intensities of time series images of a developing gel
      are determined and times until a threshold gray value is reached are calculated.
      These times are used to calculate a new grayscale image which can be analyzed
      using commercial image processing software.

PMID- 16607608
TI  - Quantitation in two-dimensional fluorescence difference gel electrophoresis:
      effect of protein fixation.
AB  - Analyzing a large number of unfixed gels in a 2-D fluorescence difference gel
      electrophoresis (2-DIGE) experiment presents a challenge of avoiding variable
      protein diffusion within and across the comparison groups. The characteristics of
      protein detection and quantitation in a 2-D differential in gel fluorescence
      experiment were compared for gels with and without protein fixation. The current
      study tests and concludes that when dealing with a large sample size with
      variable protein diffusion across the 2-D gel over a period of 2-4 days, it is a
      preferred choice to fix the gel without affecting the protein quantitation.

PMID- 16607610
TI  - The ultrastructure of MCF-10A acini.
AB  - MCF-10A human mammary epithelial cells cultured inside reconstituted basement
      membrane form acini that resemble the acinar structures of mammary lobules. This
      three-dimensional culture system has been used for identifying and characterizing
      the signal transduction pathways controlling cell proliferation and death, and
      for studying their disregulation in malignant progression. We have compared the
      ultrastructure of MCF-10A acini, MCF-10A cells grown in monolayer, and the acinar
      structures of human breast lobules. The tissue architecture of MCF-10A acini was
      formed by hemidesmosomes connected to a basement membrane and by abundant
      desmosomes between acinar cells. Intermediate filaments that joined into large
      and abundant filament bundles connected hemidesmosomes and desmosomes to sites at
      the nuclear surface. Fewer and thinner bundles of filaments were observed in
      monolayer MCF-10A cells and even fewer in breast tissue. Tight junctions were
      observed between cells in breast tissue but missing in MCF-10A acini. The
      cytoplasm of MCF-10A acinar cells had a polar organization similar to that
      observed in breast tissue, with centrosomes and the Golgi apparatus on the apical
      side of the nucleus. MCF-10A acinar nuclei had an irregular, frequently
      invaginated surface and had a single nucleolus. The distribution of
      heterochromatin was similar to that in the epithelial cells of breast tissue. The
      nuclei of monolayer MCF-10A cells had multiple nucleoli, a more regular profile,
      and less heterochromatin. Electron microscopy has the resolution required to
      survey features of MCF-10A cell and acinus architecture that may change with
      manipulations designed to induce malignant phenotypes.

PMID- 16607611
TI  - Thymosin beta4 promotes matrix metalloproteinase expression during wound repair.
AB  - Immobilized patients, diabetics, and the elderly suffer from impaired wound
      healing. The 43-amino acid angiogenic peptide thymosin beta4 (Tbeta4) has
      previously been found to accelerate dermal wound repair in rats, aged mice, and
      db/db diabetic mice. It also promotes corneal repair in both normal rats and
      mice. Because proteinases are important in wound repair, we hypothesized that
      Tbeta4 may regulate matrix metalloproteinase (MMP) expression in cells that are
      involved in wound repair. Analysis by RT-PCR of whole excised mouse dermal wounds
      on days 1, 2, and 3 after wounding showed that Tbeta4 increased several
      metalloproteinases, including MMP-2 and -9 expression by several-fold over
      control on day 2 after wounding. We further analyzed the metalloproteinases
      secreted in response to exogenous Tbeta4 by cells normally present in the wound.
      Western blot analysis of cultured keratinocytes, endothelial cells, and
      fibroblasts that were treated with increasing concentrations of Tbeta4 showed
      increases in the levels of MMP-1, -2, and -9 in a cell-specific manner. Tbeta4
      also enhanced the secretion of MMP-1 and MMP-9 by activated monocytes. The
      central actin-binding domain, amino acids 17-23, had all of the activity for
      metalloproteinase induction. We conclude that part of the wound healing activity
      of Tbeta4 resides in its ability to increase proteinase activity via its central
      actin-binding domain. Thus, Tbeta4 may play a pivotal role in extracellular
      matrix remodeling during wound repair.

PMID- 16607613
TI  - Misexpression screen for genes altering the olfactory map in Drosophila.
AB  - Despite the identification of a number of guidance molecules, a comprehensive
      picture has yet to emerge to explain the precise anatomy of the olfactory map.
      From a misexpression screen of 1,515 P{GS} lines, we identified 23 genes that,
      when forcibly expressed in the olfactory receptor neurons, disrupted the
      stereotyped anatomy of the Drosophila antennal lobes. These genes, which have not
      been shown previously to control olfactory map development, encode novel proteins
      as well as proteins with known roles in axonal outgrowth and cytoskeletal
      remodeling. We analyzed Akap200, which encodes a Protein Kinase A-binding
      protein. Overexpression of Akap200 resulted in fusion of the glomeruli, while its
      loss resulted in misshapen and ectopic glomeruli. The requirement of Akap200
      validates our screen as an effective approach for recovering genes controlling
      glomerular map patterning. Our finding of diverse classes of genes reveals the
      complexity of the mechanisms that underlie olfactory map development.

PMID- 16607614
TI  - Extracellular tumor DNA in plasma and overall survival in breast cancer patients.
AB  - In this study, we examined whether free DNA extracted from the plasma of breast
      cancer patients, characterized as tumor DNA, could predict the overall survival
      (OS) of breast cancer patients. In total, 147 patients and 35 healthy controls
      were studied. Plasma DNA was assessed in the same way as tumor DNA, following
      identification of similar alterations in polymorphic markers and TP53 gene
      mutations. Although OS was the main focus of this study, recurrence and disease
      free survival (DFS) were also analyzed. In 61 of the 142 patients, with an
      average 58 months of follow-up, a similar molecular signature in tumor and plasma
      DNA was detected. OS was 71% (95% CI, 61%-81%), and distribution as regards tumor
      plasma DNA was 59% (95% CI, 45%-73%) for positive cases and 83% (95% CI, 73%-93%)
      for negative cases (P = 0.01). Univariate analysis revealed a predictive value
      for tumor plasma DNA (P = 0.018) hazard ratio (HR) 2.5 (95% CI, 1.2-5.3), while
      multivariate analysis did not (P = 0.3), HR 1.6 (95% CI, 0.6-4.4). DFS was 37%
      (95% CI, 19%-55%) for positive patients and 75% (95% CI, 57%-93%) for negative
      patients (P = 0.005). Among the 35 recurrences observed, 25 were positive for
      tumor plasma DNA and 10 were negative, (P < 0.001). These results indicate that
      tumor plasma DNA at diagnosis can serve as a prognostic marker of the OS of
      breast cancer patients.

PMID- 16607615
TI  - Analysis of a new homozygous deletion in the tumor suppressor region at 3p12.3
      reveals two novel intronic noncoding RNA genes.
AB  - Homozygous deletions or loss of heterozygosity (LOH) at human chromosome band
      3p12 are consistent features of lung and other malignancies, suggesting the
      presence of a tumor suppressor gene(s) (TSG) at this location. Only one gene has
      been cloned thus far from the overlapping region deleted in lung and breast
      cancer cell lines U2020, NCI H2198, and HCC38. It is DUTT1 (Deleted in U Twenty
      Twenty), also known as ROBO1, FLJ21882, and SAX3, according to HUGO. DUTT1, the
      human ortholog of the fly gene ROBO, has homology with NCAM proteins. Extensive
      analyses of DUTT1 in lung cancer have not revealed any mutations, suggesting that
      another gene(s) at this location could be of importance in lung cancer initiation
      and progression. Here, we report the discovery of a new, small, homozygous
      deletion in the small cell lung cancer (SCLC) cell line GLC20, nested in the
      overlapping, critical region. The deletion was delineated using several
      polymorphic markers and three overlapping P1 phage clones. Fiber-FISH experiments
      revealed the deletion was approximately 130 kb. Comparative genomic sequence
      analysis uncovered short sequence elements highly conserved among mammalian
      genomes and the chicken genome. The discovery of two EST clusters within the
      deleted region led to the isolation of two noncoding RNA (ncRNA) genes. These
      were subsequently found differentially expressed in various tumors when compared
      to their normal tissues. The ncRNA and other highly conserved sequence elements
      in the deleted region may represent miRNA targets of importance in cancer
      initiation or progression.

PMID- 16607616
TI  - In vivo activation of SMN in spinal muscular atrophy carriers and patients
      treated with valproate.
AB  - OBJECTIVE: Spinal muscular atrophy results from loss of the survival motor neuron
      1 (SMN1) gene and malfunction of the remaining SMN2. We investigated whether
      valproic acid can elevate human SMN expression in vivo. METHODS: Blood was
      collected from 10 spinal muscular atrophy carriers and 20 spinal muscular atrophy
      patients treated with valproic acid. RESULTS: Seven of 10 carriers demonstrated
      increased SMN messenger RNA and protein levels. SMN2 messenger RNA levels were
      elevated in 7 patients and unchanged or decreased in 13 patients. INTERPRETATION:
      We provide first proof of the in vivo activation of a causative gene by valproic
      acid in an inherited disease and discuss strategies of monitoring drug response
      in patients.

PMID- 16607617
TI  - CAPN3 mutations in patients with idiopathic eosinophilic myositis.
AB  - OBJECTIVE: Eosinophilic myositis (EM) constitutes a rare pathological entity
      characterized by eosinophilic infiltration of skeletal muscles, usually
      associated with parasite infections, systemic disorders, or the intake of drugs
      or L-tryptophan. The exclusion of such causes defines the spectrum of idiopathic
      EM. Based on a protein analysis performed in one affected patient, we identified
      the gene encoding calpain-3, CAPN3, as a candidate for a subset of idiopathic EM.
      METHODS: We screened CAPN3 for mutations using DHPLC and direct sequencing in six
      unrelated patients, recruited for EM diagnosed after histological examination of
      muscle biopsy samples, without any identified causative factor. RESULTS: We
      identified CAPN3 mutations in the six unrelated patients originally diagnosed
      with idiopathic EM. INTERPRETATION: Mutations in CAPN3 can cause EM. Thus, a
      subset of idiopathic EM is genetically determined, with an autosomal recessive
      mode of inheritance. Patients presented with a triad that appears to be
      indicative of CAPN3 mutations: (1) EM in the first decade, (2) elevated serum
      creatine phosphokinase levels (isolated or with little corresponding weakness),
      and (3) inconstant peripheral hypereosinophilia. However, that EM represents a
      distinct phenotype associated to CAPN3 mutations or, rather, an early
      histopathological picture of LGMD2A must be further evaluated. Our findings
      should be of interest toward further investigating the role of calpain-3 in
      skeletal muscle. Furthermore, patients with idiopathic EM should undergo calpain
      3 protein analysis and be considered for subsequent molecular analysis of the
      CAPN3 gene.

PMID- 16607618
TI  - Photodynamic therapy: combined modality approaches targeting the tumor
      microenvironment.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic therapy causes direct cytotoxicity to
      malignant cells within a tumor. Photodynamic therapy (PDT) can also have both
      direct and indirect effects upon various non-malignant components of the tumor
      microenvironment. This action can lead to PDT-mediated angiogenesis and
      inflammation, which are emerging as important determinants of PDT responsiveness.
      STUDY DESIGN/MATERIALS AND METHODS: Preclinical studies have been performed to
      document how PDT modulates the tumor microenvironment. The expression, function,
      and treatment relevance of angiogenic growth factors, proteinases, and
      inflammatory molecules have been monitored following PDT using mouse tumor
      models. RESULTS: Photofrin-mediated PDT was shown to be a strong activator of
      VEGF, MMPs, and COX-2 derived prostaglandins within the tumor microenvironment.
      Inhibitors that target these angiogenic and pro-survival molecules can enhance
      the effectiveness of PDT. CONCLUSIONS: Improvements in PDT tumor responsiveness
      may be achieved by employing combined modality regimens targeting malignant cells
      as well as treatment-induced angiogenesis and/or inflammation.

PMID- 16607619
TI  - Expression of nidogens in rat uterus and embryo during decidualization and
      implantation.
AB  - The purpose of this study was to demonstrate the expression of nidogen-1 and
      nidogen-2 and their possible role in decidualization and implantation events
      during early pregnancy in rats. The tissue samples were examined from pregnant
      animals between gestational days 1-8 using immunocytochemistry. The uterine
      luminal epithelium, the glandular epithelium, and the myometrial smooth muscle
      cells stained strongly from gestational days 1-8 with both nidogen antibodies. At
      day 4 the decidual reaction areas began to appear in the stromal matrix and
      immunostaining of both nidogens revealed that the basement membrane of the
      surface epithelium was discontinuous. The differentiation of stromal cells into
      decidual cells was seen at gestational day 5 and both nidogens were weakly
      expressed in the decidualizing cells. At day 6, nidogen-2 immunoreactivity was
      higher in the primary decidual cells close to the embryo than nidogen-1, and
      during development of the decidual tissue both nidogens appeared in the
      endometrial stromal cells. At day 7, while expression of both nidogens declined
      in the primary decidual cells, their expression was markedly observed in the
      secondary decidual cells close to the myometrium. At day 8, expression of both
      nidogens was also observed to increase in the primary decidual cells. While
      nidogen-2 expression was seen in the parietal endoderm and primary ectoderm of
      the rat embryos at this developmental stage, nidogen-1 expression was only
      detected in the parietal endoderm. These results indicate that nidogen-1 and
      nidogen-2 could play important roles during embryogenesis, decidualization, and
      implantation in the endometrium of rat uterus.

PMID- 16607620
TI  - American Society of Pediatric Hematology/Oncology 19th Annual Meeting, San
      Francisco, California, USA, April 29-May 2, 2006. Abstracts.

PMID- 16607621
TI  - Exposure to AC and DC magnetic fields induces changes in 5-HT1B receptor binding
      parameters in rat brain membranes.
AB  - The binding properties of the G-protein coupled receptor (GPCR) serotonin 5-HT1B
      receptor were studied under exposure to AC (50 and 400 Hz) and DC magnetic fields
      (MF) in rat brain membranes. This was an attempt at replicating the positive
      findings of Massot et al. In saturation experiments using [3H]5-HT, 1-h exposures
      at 1.1 mT(rms) 50 Hz caused statistically significant increases in both the K(D)
      and B(max) binding parameters, from 1.74 +/- 0.3 to 4.51 +/- 0.86 nM and from
      1428 +/- 205 to 2137 +/- 399 CPM, respectively, in good agreement with previous
      results. Exposure of the membranes at 400 Hz 0.675 mT(rms) did not elicit a
      larger increase in K(D) in spite of a much larger induced current density. DC
      fields (1.1 and 11 mT) had a lesser effect compared to AC fields at low values of
      K(Dsham), but decreased the affinity at higher values of K(Dsham). Modeling of
      the receptor-ligand-G protein interactions using the extended ternary complex
      model yielded good fits for all our data and that of Massot et al., showing that
      the AC field may act by decreasing the ability of the G-protein to alter the
      ligand-receptor affinity. The hypothesis is that the bipolar nature of the AC
      field explains the different nature of the effects observed with AC and DC
      exposures. These findings constitute one of the few documented pieces of evidence
      for cell-free effects of DC and extremely low frequency (ELF) AC MFs in the mT
      range.

PMID- 16607622
TI  - Interference of programmed electromagnetic stimulation with pacemakers and
      automatic implantable cardioverter defibrillators.
AB  - A commercially available magnetic therapy system, designed for clinical
      application as well as for private use without medical supervision, was examined
      with respect to its potential for causing electromagnetic interference with
      implantable pacemakers (PMs) and automatic implantable cardioverter
      defibrillators (AICDs). A sample of 15 PMs and 5 AICDs were experimentally
      investigated. Each of the implants was realistically positioned in a homogeneous,
      electrically passive torso phantom and exposed to the magnetic fields of the
      system's applicators (whole body mat, cushion, and bar applicator). The detection
      thresholds of the implants were programmed to maximum sensitivity and both
      unipolar as well as bipolar electrode configurations were considered. The
      evaluation of possible interferences was derived from the internal event storages
      and pacing statistics recorded by the implants during exposure. Any "heart
      activity" recorded by the implants during exposure was interpreted as a potential
      interference, because the implant obviously misinterpreted the external
      interference signal as a physiological signal. Only cases without any recorded
      "heart activity" and with nominal pacing rates (as expected from the program
      parameter settings) of the implants were rated as "interference-free." Exposure
      to the whole body mat (peak magnetic induction up to 265 microT) did not show an
      influence on PMs and AICD in any case. The cushion applicator at the highest
      field intensity (peak magnetic induction up to 360 microT) led to atrial sensing
      defects in four PM models with unipolar electrode configuration. Under bipolar
      electrode configuration no disturbances occurred. The bar applicator led to
      sensing problems and consecutively reduced pacing rates in all tested PM models
      under unipolar electrode configuration and maximum field intensity (peak magnetic
      induction up to 980 microT). Bipolar electrode configuration resolved the
      problem. The investigated AICDs did not show malfunctions under any investigated
      condition. In conclusion, the examined PEMF therapy system did not interfere with
      the investigated implantable cardiac devices with bipolar electrode
      configuration. However, unipolar electrode configuration in pacemakers seems to
      be potentially hazardous during application of the examined PEMF therapy system.

PMID- 16607623
TI  - The influence of continuous exposure to 50 Hz electric field on nerve
      regeneration in a rat peroneal nerve crush injury model.
AB  - The effect of power frequency electric field (EF) on nerve regeneration was
      investigated on a rat peroneal nerve crush injury model. The animals were
      assigned to three groups: 50 Hz EF and Static EF groups were exposed at 10 kV/m.
      The sham group was kept in the same setting without any EF applications. EF was
      uninterruptedly applied for 21 days postoperatively. Repeated measures analysis
      of daily walking tracks during EF exposure demonstrated lower toe spread recovery
      (TSR) in the 50 Hz EF group. Significant difference across the groups was found
      only at days 7, 8, 12, 16, 17, 20, and 21 when TSR was analyzed for each
      measurement time. Print length recovery and peroneal function index did not
      differ across the groups. Walking track parameters were found to recover to their
      baseline values by day 28 in all groups. Day 14 but not day 21 measurements
      revealed smaller nerve cross-sectional area, lower total regenerating axon area,
      and higher mean myelin debris area in 50 Hz EF group. Both day 14 and 21
      measurements revealed higher total myelin debris area, lower EDL muscle weight,
      and lack of significant enlargement in nerve cross-section distal to the injury,
      compared to the normal counterpart in 50 Hz EF group. All differences were in
      keeping with lower rates of Wallerian degeneration and nerve regeneration in 50
      Hz EF group. When walking track, histomorphometry and muscle weight are
      considered individually, their differences across the groups may appear to be
      subtle to derive a conclusion for a 50 Hz EF effect. However, their concordance
      with each other in direction of effect suggests that continuous 50 Hz EF exposure
      has a weak effect that is detrimental mostly to the rate of early nerve
      regeneration in this axonotmetic injury model. Recovery of walking tracks was not
      different between Static EF and Sham groups. This suggests that the surface
      charges that may indirectly affect walking behaviors of the rats, do not account
      for the lower recovery of TSR in 50 Hz EF group. Differences in nerve
      regeneration between 50 Hz EF and Static EF groups suggests that electric
      induction may be required for pure EF effects even though the estimated density
      of induced fields is not above the endogenous background level for the 50 Hz EF
      exposure in this study.

PMID- 16607624
TI  - Improving the power of association tests for quantitative traits in family
      studies.
AB  - Association mapping based on family studies can identify genes that influence
      complex human traits while providing protection against population
      stratification. Because no gene is likely to have a very large effect on a
      complex trait, most family studies have limited power. Among the commonly used
      family-based tests of association for quantitative traits, the quantitative
      transmission-disequilibrium tests (QTDT) based on the variance-components model
      is the most flexible and most powerful. This method assumes that the trait values
      are normally distributed. Departures from normality can inflate the type I error
      and reduce the power. Although the family-based association tests (FBAT) and
      pedigree disequilibrium tests (PDT) do not require normal traits, nonnormality
      can also result in loss of power. In many cases, approximate normality can be
      achieved by transforming the trait values. However, the true transformation is
      unknown, and incorrect transformations may compromise the type I error and power.
      We propose a novel class of association tests for arbitrarily distributed
      quantitative traits by allowing the true transformation function to be completely
      unspecified and empirically estimated from the data. Extensive simulation studies
      showed that the new methods provide accurate control of the type I error and can
      be substantially more powerful than the existing methods. We applied the new
      methods to the Collaborative Study on the Genetics of Alcoholism and discovered
      significant association of single nucleotide polymorphisms (SNP) tsc0022400 on
      chromosome 7 with the quantitative electrophysiological phenotype TTTH1, which
      was not detected by any existing methods. We have implemented the new methods in
      a freely available computer program.

PMID- 16607625
TI  - The v-MFG test: investigating maternal, offspring and maternal-fetal genetic
      incompatibility effects on disease and viability.
AB  - The MFG test is a family-based association test that detects genetic effects
      contributing to disease in offspring, including offspring allelic effects,
      maternal allelic effects and MFG incompatibility effects. Like many other family
      based association tests, it assumes that the offspring survival and the offspring
      parent genotypes are conditionally independent provided the offspring is
      affected. However, when the putative disease-increasing locus can affect another
      competing phenotype, for example, offspring viability, the conditional
      independence assumption fails and these tests could lead to incorrect conclusions
      regarding the role of the gene in disease. We propose the v-MFG test to adjust
      for the genetic effects on one phenotype, e.g., viability, when testing the
      effects of that locus on another phenotype, e.g., disease. Using genotype data
      from nuclear families containing parents and at least one affected offspring, the
      v-MFG test models the distribution of family genotypes conditional on offspring
      phenotypes. It simultaneously estimates genetic effects on two phenotypes,
      viability and disease. Simulations show that the v-MFG test produces accurate
      genetic effect estimates on disease as well as on viability under several
      different scenarios. It generates accurate type-I error rates and provides
      adequate power with moderate sample sizes to detect genetic effects on disease
      risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data
      from study participants with rheumatoid arthritis (RA) and their parents, we show
      that the v-MFG test successfully detects an MFG incompatibility effect on RA
      while simultaneously adjusting for a possible viability loss.

PMID- 16607626
TI  - Optimal two-stage genotyping designs for genome-wide association scans.
AB  - The much-anticipated fixed-array, genome-wide SNP genotyping technologies make
      large-scale genome-wide association scans now possible for large numbers of
      subjects. In this paper we reconsider the problem (Satagopan and Elston [2003]
      Genet Epidemiol 25:149-157) of optimizing a two-stage genotyping design to deal
      with important new issues that are relevant when studies are expanded from
      candidate gene size to a genome-wide scale. We investigate how the basic two
      stage genotyping approach, in which all markers are genotyped in an initial group
      of subjects (stage I) and only the promising markers are genotyped in additional
      subjects (stage II), can be used to reduce genotyping cost in a genome-wide case
      control association study even after allowing for much higher per genotype costs
      using specially designed assays in stage II, compared to the fixed array of SNPs
      used in stage I. In addition, we consider the problem of using measured SNPs to
      make (imperfect) prediction of unmeasured SNPs for association tests of all SNPs
      (measured or unmeasured) genome wide and the utility of expanding genotyping
      densities in stage II in the regions where significant associations were detected
      in stage I. Under a set of reasonable but conservative assumptions, we derive
      optimal two-stage design configurations (sample sizes and the thresholds of
      significance in both stages) with these optimal designs depending both on the
      total number of markers tested and upon the ratios of cost in stage II versus
      stage I. In addition we show how existing software for power and sample size
      calculations can be used for the purpose of designing two-stage studies, for a
      wide range of assumptions about the number of markers genotyped and the costs of
      genotyping in each stage of the study.

PMID- 16607627
TI  - Case report: combination therapy with granulocyte apheresis and infliximab for
      refractory Crohn's disease.

PMID- 16607628
TI  - Study of coagulation factor activities in apheresed thawed fresh frozen plasma at
      1-6 degrees C for five days.
AB  - The concern for the loss of activities of coagulation factors in thawed fresh
      frozen plasma kept at 1-6 degrees C for long periods has prevented transfusion
      services from using thawed plasma beyond 24 hours of storage. There is no mention
      of the method of collection of the plasma and/or the study of the bacterial
      growth in the studies reported in the literature. The present project was
      undertaken to investigate coagulation factor activities and bacterial growth in
      apheresed fresh plasma. Twenty apheresed plasma units from different blood groups
      were used. After the 24-hour expiration time of the thawed plasma kept at 1-6
      degrees C, aliquots were taken at day 1, day 3, and day 5 of expiration time and
      were immediately frozen at -70 degrees C. Samples were assayed for activities of
      coagulation factors II, V, VII, VIII, X, XI, and fibrinogen (Fib). Our study
      reveals no statistically significant change in activities of coagulation factors
      II, VII, X, XI, and fibrinogen from day 1 to day 5 storage of plasma at 1-6
      degrees C; however, there is a mean decrease of 8.8 and 14.3% in activities of
      factors V and VIII, respectively. All culture samples taken on day 5 storage were
      negative at 7 days. In conclusion, our results do not show a significant change
      in the activity of most coagulation factors in the thawed apheresis plasma stored
      at 1-6 degrees C over a 5-day period. Hence, it is feasible to transfuse the
      plasma beyond the 24-hour period without compromising the clinical outcome of
      patients with coagulopathy.

PMID- 16607629
TI  - Activation of myosin in HeLa cells causes redistribution of focal adhesions and F
      actin from cell center to cell periphery.
AB  - Activation of actomyosin II by phosphorylation of its regulatory light chain is
      one of the main factors involved in the regulation of cytoskeletal dynamics.
      Phosphorylation of myosin regulatory light chain may be mediated directly and
      indirectly by several kinases including myosin light chain kinase (MLCK) and
      kinases activated by small GTP-binding proteins. Most of the myosin kinases,
      including PAK, can also interact with other proteins through binding sites
      located outside of their catalytic domains. In an attempt to study the effects
      due only to phosphorylation of myosin light chain, we expressed the
      constitutively active catalytic domain of ameba PAK in HeLa cells. The catalytic
      domain phosphorylates myosin light chain in vitro with high specific activity but
      has none of the sequences that target mammalian PAK to other proteins and
      membranes. Expression of the catalytic domain caused disassembly of focal
      adhesions and stress fibers in the cell center and accumulation of focal
      adhesions and F-actin at the cell periphery. There was a twofold increase in the
      phosphorylation level of endogenous myosin light chain and changes in cell shape
      consistent with enhanced cell contractility. The phenotype was independent of
      MLCK, ROCK, MEK, Rac, and Rho activities but was abolished by blebbistatin, a
      specific inhibitor of myosin II activity. Our data are consistent with myosin
      being directly phosphorylated by the expressed catalytic domain of ameba PAK with
      the induced phenotype resulting from cell retraction driven by contraction of
      peripheral actomyosin. The phenotype induced by expression of the catalytic
      domain is reminiscent of that caused by expression of active mammalian PAK,
      suggesting that myosin phosphorylation may play an important role in PAK-induced
      cytoskeletal changes. The catalytic domain of ameba PAK may be a useful tool for
      studying the effects of myosin light chain phosphorylation in other cells.

PMID- 16607630
TI  - The effect of combined hypergravity and micro-grooved surface topography on the
      behaviour of fibroblasts.
AB  - This study evaluated in vitro the differences in morphological behaviour between
      fibroblast cultured on smooth and micro-grooved substrata (groove depth: 1 mum,
      width: 1, 2, 5, 10 microm), which undergo artificial hypergravity by
      centrifugation (10, 24 and 50 g; or 1 g control). The aim of the study was to
      clarify which of these parameters was more important to determine cell behaviour.
      Morphological characteristics were investigated using scanning electron
      microscopy and fluorescence microscopy in order to obtain qualitative information
      on cell spreading and alignment. Confocal laser scanning microscopy visualised
      distribution of actin filaments and vinculin anchoring points through
      immunostaining. Finally, expression of collagen type I, fibronectin, and alpha(1)
      and beta(1)-integrin were investigated by PCR. Microscopy and image analysis
      showed that the fibroblasts aligned along the groove direction on all textured
      surfaces. On the smooth substrata (control), cells spread out in a random
      fashion. The alignment of cells cultured on grooved surfaces increased with
      higher g-forces until a peak value at 25 g. An ANOVA was performed on the data,
      for all main parameters: topography, gravity force, and time. In this analysis,
      all parameters proved significant. In addition, most gene levels were reduced by
      hypergravity. Still, collagen type 1 and fibronectin are seemingly unaffected by
      time or force. From our data it is concluded that the fibroblasts primarily
      adjust their shape according to morphological environmental cues like substratum
      surface whilst a secondary, but significant, role is played by hypergravity
      forces.

PMID- 16607631
TI  - Plasma exchanges do not increase red blood cell transfusion efficiency in severe
      autoimmune hemolytic anemia: a retrospective case-control study.
AB  - Severe autoimmune hemolytic anemia (AIHA) can cause life-threatening hemolysis
      requiring red blood cell transfusions (RBT). The efficiency of RBT could be
      improved with the use of plasma exchanges (PEx) before RBT. The objective of this
      study was to assess the effectiveness of PEx in severe AIHA of adults. All adult
      patients with severe AIHA requiring RBT were included in this single center
      retrospective case-control study. The end point was change in hemoglobin (Hb)
      level after RBT, depending on whether PEx was done (experimental group) or not
      (control group). Thirty-one sessions of RBT following PEx were performed on the 5
      patients of the experimental group and were compared with the 7 sessions of BT
      without PEx performed on the 4 patients of the control group. Despite a lower
      mean Hb value before the session of RBT (5.7 g/dl vs. 7.2 g/dl, P = 0.04) in the
      control group, the mean Hb value 5 (4-7) days following RBT (8.7 g/dl vs. 8.6
      g/dl, P = 0.85) was not different in the experimental and in the control group,
      respectively. In a second analysis in which each patient was his own control (31
      sessions of RBT following PEx vs. 51 sessions of RBT alone), the gain in Hb was
      not different (1.4 g/dl vs. 1.9 g/dl, P = 0.67). When RBT are required in severe
      AIHA of adults, the use of a single PEx before BT does not increase the
      efficiency of RBT based on day 5 evaluation.

PMID- 16607632
TI  - Treatment of extensive chronic graft-versus-host disease with extracorporeal
      photochemotherapy.
AB  - Extracorporeal photochemotherapy (ECP; photopheresis), an immunomodulatory
      therapy developed for cutaneous T-cell lymphoma, has shown promise in treating
      chronic graft-versus-host disease (cGvHD) in uncontrolled studies. The purpose of
      this study was to further examine the effects of ECP on cGvHD. ECP (administered
      initially 3 times weekly on alternating days) was retrospectively evaluated in 14
      patients with extensive cGvHD following allogeneic hematopoietic stem cell
      transplantation. The median time from transplantation to ECP initiation was 29
      months (range, 5-96 months). The median number of concomitant baseline treatments
      per patient was 3 (range, 0-5). During a median ECP duration of 17 months (range,
      3-44 months), 3 patients (21%) achieved a complete cutaneous response (100%
      improvement), 4 patients (29%) achieved a partial cutaneous response (> or =50%
      improvement), and 7 patients (50%) had stable skin disease. The median time to
      response was 6 months (range, 2-15 months), and the median response duration was
      5 months (range, 1-31 months). At endpoint, responses were ongoing in 4 patients.
      Resolution or improvement was noted in arthralgia (5/7 patients), oral changes
      (3/7), elevated liver enzymes (3/5), dry eyes (2/5), joint stiffness (3/3),
      pulmonary disease (1/3), and thrombocytopenia (1/1). Because of a favorable
      response, 11 of 13 patients (85%) who received prednisone at baseline were able
      to taper (7/13; 54%) or discontinue (4/13; 31%) this medication, and 12 of 14
      patients (86%) were able to taper (11/14; 79%) or discontinue (1/14; 7%) ECP.
      Five-year posttransplantation survival was 77%. Our results suggest that
      adjunctive ECP improves cutaneous and extracutaneous manifestations of cGvHD and
      has a steroid-sparing effect.

PMID- 16607633
TI  - Inhibiting matrix metalloproteinases with prinomastat produces abnormalities in
      fetal growth and development in rats.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) play key roles in remodeling of the
      extracellular matrix during embryogenesis and fetal development. The objective of
      this study was to determine the effects of prinomastat, a potent selective MMP
      inhibitor, on fetal growth and development. METHODS: Prinomastat (25, 100, 250
      mg/kg/day, p.o.) was administered to pregnant female Sprague-Dawley rats on
      gestational days (GD) 6-17. A Cesarian section was carried out on GD 20 and the
      fetuses were evaluated for viability and skeletal and soft tissue abnormalities.
      RESULTS: Prinomastat treatment at the 250 mg/kg/day dose produced a decrease in
      body weight and food consumption in the dams. A dose-dependent increase in post
      implantation loss was observed in the 100 and 250 mg/kg/day-dose groups,
      resulting in only 22% of the dams having viable litters for evaluation at the 250
      mg/kg/day dose. Fetal skeletal tissue variations and malformations were present
      in all prinomastat treated groups and their frequency increased with dose.
      Variations and malformation in fetal soft tissue were also increased at the 100
      and 250 mg/kg/day doses. Prinomastat also interfered with fetal growth of rat
      embryo cultures in vitro. CONCLUSIONS: These data confirm that MMP inhibition has
      a profound effect on fetal growth and development in vivo and in vitro.

PMID- 16607634
TI  - Embryotoxicity of oral administered chlorothalonil in mice.
AB  - BACKGROUND: Chlorothalonil (2,4,5,6-tetrachloroisophthalonitril), the nephrotoxic
      fungicide, was examined for its potential to produce developmental toxicity in
      mice after oral administration. METHODS: Pregnant ICR (CD-1) mice were given
      sublethal doses of 0 (corn oil), 100, 400, and 600 mg/kg/day chlorothalonil by
      gavage on gestation days (GD) 6-15. RESULTS: Maternal effects in 400 and 600
      mg/kg/day dose groups included signs of toxicity such as weakness and depression
      in the maternal activity, and reduction in body weight and weight gain. No
      maternal toxicity was apparent in the 100 mg/kg/day dose group. Maternal exposure
      to chlorothalonil during organogenesis significantly affected the number of live
      fetuses, early resorption, and mean fetal weight in the 400 and 600 mg/kg/day
      dose groups. No external, visceral, and skeletal abnormalities were observed
      among any of the treated groups compared to the control. CONCLUSIONS: On the
      basis of the present results chlorothalonil can produce clinical signs of
      toxicity and fetotoxicity without teratogenic effects at 400 and 600 mg/kg/day
      dose groups.

PMID- 16607635
TI  - Mass probe-assisted ionization method for total analysis of biomolecules with
      electrospray ionization-mass spectrometry.
AB  - In this paper, we review the mass probes used for the derivation of a variety of
      biomolecules efficiently detected by the electrospray ionization-mass
      spectrometry and mass probe-assisted ionization method for total analysis and
      determination by consecutive detection with a single instrument. We describe mass
      probes for a variety of molecules including proteins, nucleobases, metallic
      cations, and other small molecules.

PMID- 16607636
TI  - Unicellular pheromone glands of the pentatomid bug Nezara viridula (Heteroptera:
      Insecta): ultrastructure, classification, and proposed function.
AB  - Male Nezara viridula produce sex pheromones from many independent single cells,
      each with a duct that opens onto the ventral abdominal surface. Despite the
      presence of a long duct and an associated end complex (in the form of a cupule
      and microvillus saccule), the structural organization of the cells that comprise
      the gland conform to Class 1 epidermal gland cell classification : a single cell
      surrounds the entire secretory complex. Each cuticular cupule contains a central
      bed of filaments and opens into a narrow tubular ductule that leads from the base
      of the cupule through the epidermis to the cuticle to open externally as a pore.
      The cuticle of the cupule is continuous with that of the ductule and has the
      appearance of three layers, although the inner (middle) layer may be a gap formed
      during construction of the complex. In young adult males, just molted, the
      ultrastructure of the cells and their inclusions indicate that they are not
      active. The region of the cell that is distal to the abdominal cuticle is reduced
      and the proximal region, surrounding the duct, is enlarged when compared with
      sexually mature (3-4 weeks old) adult males. At maturity the pheromone cells are
      enlarged distally around the cupule, but are reduced to a narrow sleeve
      proximally, around the ductule. Two characteristic cell profiles are evident,
      based on the shape of the cupule and the organelle content. Type A shows a broad
      opening to the cupule, an abundance of mitochondria, and few vesicular bodies.
      Type B has an elongated, narrow, vase-like opening to the cupule, few
      mitochondria, and numerous vesicular bodies. Type B cells are smaller and more
      abundant than Type A. Distribution within the epidermal layer also differs. It is
      likely that the different types represent cells producing different secretion
      profiles. However, the secretions retained by the standard fixation protocol
      within mature cells of both types look similar and appear to collect as
      crystalline bodies within the lumen. This may represent a common storage
      mechanism.

PMID- 16607637
TI  - Expression of 18-wheeler in the follicle cell epithelium affects cell migration
      and egg morphology in Drosophila.
AB  - The Drosophila ovary is a model system for examining the genetic control of
      epithelial morphogenesis. The somatic follicle cells form a polarized epithelium
      surrounding the 16-cell germ line cyst. The integrity of this epithelium is
      essential for the successful completion of oogenesis. Reciprocal signaling
      between germ line and somatic cells establishes embryonic and eggshell polarity.
      The follicle cells are responsible for shaping the egg and secreting the
      eggshell. Follicle cells at the boundary between the nurse cells and the oocyte
      migrate centripetally to cover the anterior end of the oocyte and secrete the
      operculum. Dorsal anterior main body follicle cells undergo elaborate patterning
      to produce the dorsal appendages. We have examined the expression of the Toll
      like receptor, 18-wheeler (18w), in the ovary and find it to be restricted to
      subpopulations of follicle cells. Females carrying loss-of-function 18w mutant
      clones in their ovaries show delayed follicle cell migrations. The eggs laid by
      such females also show morphological defects in egg shape and dorsal appendage
      morphology. We propose that the 18W protein plays an adhesive or signaling role
      in regions of the epithelium engaged in cell migration.

PMID- 16607639
TI  - Xenopus fibrillin is expressed in the organizer and is the earliest component of
      matrix at the developing notochord-somite boundary.
AB  - We identify a Xenopus fibrillin homolog (XF), and show that its earliest
      developmental expression is in presumptive dorsal mesoderm at gastrulation, and
      that XF expression is regulated by mesoderm-inducing factors in animal cap
      assays. XF protein is also first detected in presumptive mesoderm, but is
      concentrated specifically into extracellular-matrix structures that begin to
      develop de novo by mid-gastrulation at both of the bilateral presumptive
      notochord-somite boundaries. Later in embryogenesis, XF protein is localized to
      the extracellular matrix at tissue boundaries, where it is found surrounding the
      notochord, the somites, and the neural tube, as well as under the epidermis. This
      pattern of protein deposition combines to give the appearance of an "embryonic
      skeleton," suggesting that one role for XF is to serve as a mechanical element in
      the embryo prior to bone deposition.

PMID- 16607638
TI  - Jag2-Notch1 signaling regulates oral epithelial differentiation and palate
      development.
AB  - During mammalian palatogenesis, palatal shelves initially grow vertically from
      the medial sides of the paired maxillary processes flanking the developing tongue
      and subsequently elevate and fuse with each other above the tongue to form the
      intact secondary palate. Pathological palate-mandible or palate-tongue fusions
      have been reported in humans and other mammals, but the molecular and cellular
      mechanisms that prevent such aberrant adhesions during normal palate development
      are unknown. We previously reported that mice deficient in Jag2, which encodes a
      cell surface ligand for the Notch family receptors, have cleft palate associated
      with palate-tongue fusions. In this report, we show that Jag2 is expressed
      throughout the oral epithelium and is required for Notch1 activation during oral
      epithelial differentiation. We show that Notch1 is normally highly activated in
      the differentiating oral periderm cells covering the developing tongue and the
      lateral oral surfaces of the mandibular and maxillary processes during palate
      development. Oral periderm activation of Notch1 is significantly attenuated
      during palate development in the Jag2 mutants. Further molecular and
      ultrastructural analyses indicate that oral epithelial organization and periderm
      differentiation are disrupted in the Jag2 mutants. Moreover, we show that the
      Jag2 mutant tongue fused to wild-type palatal shelves in recombinant explant
      cultures. These data indicate that Jag2-Notch1 signaling is spatiotemporally
      regulated in the oral epithelia during palate development to prevent premature
      palatal shelf adhesion to other oral tissues and to facilitate normal adhesion
      between the elevated palatal shelves.

PMID- 16607640
TI  - Predictable mosaic transgene expression in ascidian embryos produced with a
      simple electroporation device.
AB  - Two customized electroporators were specifically designed for creating transgenic
      ascidian embryos. These electroporators were simple to build, inexpensive, and
      produced transgenic embryos with efficiencies that equaled or rivaled
      commercially available machines. A key design feature of these machines resulted
      in the generation of consistent electroporation pulses providing repeatability
      between experiments. These devices were used to optimize experimental parameters
      allowing for the creation of transient transgenic embryos with predictable
      patterns of mosaic transgene expression. We used these new electroporators to
      examine the expression of two different fluorescent protein reporter genes with
      regard to embryonic cell lineage. In general, transgene expression followed the
      embryonic cell lineage and coelectroporated transgenes were always expressed in
      the same embryonic cells. Our analysis also indicated that, during development,
      transgenes could be lost from embryonic cells, suggesting that transgenes may be
      present in extrachromosomal arrays, as has been observed in other organisms. Our
      new electroporator designs will allow ascidian researchers to inexpensively
      produce transgenic ascidians and should prove useful for adapting the
      electroporation technique to other marine embryo systems.

PMID- 16607641
TI  - Stromal Hoxa5 function controls the growth and differentiation of mammary
      alveolar epithelium.
AB  - Recent progress has enlightened the involvement of Hox genes in organogenesis.
      Several Hox genes are expressed in normal and neoplastic mammary glands. Using
      Hoxa5 mutant mice, we showed that Hoxa5-/- females present nursing defects.
      Characterization of the Hoxa5-/- mammary gland phenotype reveals changes in
      proliferation and differentiation of the epithelium of nulliparous and pregnant
      Hoxa5-/- females that precede the abnormal secretory activity at parturition.
      These defects likely underlie the incapacity of Hoxa5-/- dams to properly feed
      their pups. Hoxa5 expression is restricted to the mammary stroma at specific
      stages of mammary gland development. The loss of Hoxa5 function causes
      accelerated lobuloalveolar epithelium development, a phenotype that can be
      rescued upon grafting of mutant mammary epithelium into wild-type fat pads.
      Conversely, reciprocal grafting experiments demonstrate that Hoxa5-/- stroma
      cannot support normal proliferation of wild-type mammary epithelium. These data
      establish the essential contribution of Hoxa5 to mammary epithelium instruction
      by means of mesenchymal-epithelial crosstalk.

PMID- 16607642
TI  - Isolation and characterization of a novel gene, xMADML, involved in Xenopus
      laevis eye development.
AB  - We have identified Xenopus MADM-like (xMADML), a Xenopus laevis gene related to
      the murine MADM and the human NRBP genes. xMADML is expressed throughout early
      development and is expressed most strongly in the developing lens and more weakly
      in the retina and other anterior tissues. We demonstrate that disruption of
      xMADML translation by means of morpholino injection results in impaired retina
      and lens development. Reciprocal transplantation of the presumptive lens ectoderm
      between morpholino-injected embryos and those injected solely with a dextran
      lineage tracer demonstrates that xMADML is necessary in both the lens and the
      retina for correct development of these eye tissues. Analysis of gene expression
      after knockdown of xMADML revealed significant alterations in the expression of
      some genes, including Pax6, xSix3, Sox2, and Sox3, suggesting that xMADML plays a
      role in regulating gene expression during development of the eye. This
      investigation is the first in vivo study examining the developmental role of this
      novel gene and reveals an important role of xMADML in eye tissue development and
      differentiation.

PMID- 16607643
TI  - Visualizing neurons one-by-one in vivo: optical dissection and reconstruction of
      neural networks with reversible fluorescent proteins.
AB  - A great many axons and dendrites intermingle to fasciculate, creating synapses as
      well as glomeruli. During live imaging in particular, it is often impossible to
      distinguish between individual neurons when they are contiguous spatially and
      labeled in the same fluorescent color. In an attempt to solve this problem, we
      have taken advantage of Dronpa, a green fluorescent protein whose fluorescence
      can be erased with strong blue light, and reversibly highlighted with violet or
      ultraviolet light. We first visualized a neural network with fluorescent Dronpa
      using the Gal4-UAS system. During the time-lapse imaging of axonal navigation, we
      erased the Dronpa fluorescence entirely; re-highlighted it in a single neuron
      anterogradely from the soma or retrogradely from the axon; then repeated this
      procedure for other single neurons. After collecting images of several individual
      neurons, we then recombined them in multiple pseudo-colors to reconstruct the
      network. We have also successfully re-highlighted Dronpa using two-photon
      excitation microscopy to label individual cells located inside of tissues and
      were able to demonstrate visualization of a Mauthner neuron extending an axon.
      These "optical dissection" techniques have the potential to be automated in the
      future and may provide an effective means to identify gene function in
      morphogenesis and network formation at the single cell level.

PMID- 16607644
TI  - Differential role of 14-3-3 family members in Xenopus development.
AB  - The 14-3-3 proteins are intracellular dimeric phosphoserine/threonine binding
      molecules that participate in signal transduction, checkpoint control, nutrient
      sensing, and cell survival pathways. Previous work established that 14-3-3
      proteins are required in early Xenopus laevis development by modulating
      fibroblast growth factor signaling. Although this general requirement for 14-3-3
      proteins in Xenopus early embryogenesis is established, there is no information
      about the specific role of individual 14-3-3 genes. Botanical studies previously
      demonstrated functional specificity among 14-3-3 genes during plant development.
      In this study, an antisense morpholino oligo microinjection approach was used to
      characterize the requirement for six specific 14-3-3 family members in Xenopus
      embryogenesis. Microinjection experiments followed by Western blot analysis
      showed that morpholinos reduced specific 14-3-3 protein levels. Embryos lacking
      specific 14-3-3 isoforms displayed unique phenotypic defects. In particular,
      reduction of 14-3-3 tau (tau) protein, and to a lesser extent, 14-3-3 epsilon
      (epsilon), resulted in embryos with prominent gastrulation and axial patterning
      defects and reduced mesodermal marker gene expression. In contrast, reduction of
      14-3-3 zeta (zeta) protein caused no obvious phenotypic abnormalities. Reduction
      of 14-3-3 gamma (gamma) protein resulted in eye defects without gastrulation
      abnormalities. Therefore, individual 14-3-3 genes have separable functions in
      vertebrate embryonic development.

PMID- 16607645
TI  - Inhibition of SMAD2 expression prevents murine palatal fusion.
AB  - Transforming growth factor (TGF)-beta 3 is known to regulate the disappearance of
      murine medial edge epithelium (MEE) during palatal fusion. Our previous studies
      showed that SMAD2, a TGF-beta signaling mediator, was expressed and
      phosphorylated primarily in the MEE and that SMAD2 phosphorylation in the MEE was
      temporospatially regulated by TGF-beta 3. The goal of this study was to examine
      the requirement for SMAD2 to complete the developmental events necessary for
      palatal fusion. SMAD2 expression was inhibited with Smad2 siRNA transfection into
      palatal tissues in vitro. The results showed that Smad2 siRNA transfection
      resulted in the maintenance of MEE cells in the palatal midline. Western blot and
      immunofluorescence analyses confirmed that the endogenous SMAD2 and phospho-SMAD2
      levels were reduced following siRNA transfection. The SMAD3 level was not altered
      by the Smad2 siRNA transfection. The persistence of the MEE and the decreased
      SMAD2/phospho-SMAD2 levels were coincident with increased MEE cell proliferation.
      Addition of exogenous TGF-beta 3 increased p-SMAD2 level but not the total SMAD2
      level. Therefore, exogenous TGF-beta 3 was not able to induce p-SMAD2 enough to
      rescue the palatal phenotype in the Smad2 siRNA group. The results indicated that
      the endogenous SMAD2 level is crucial in the regulation of disappearance of MEE
      during palatal fusion.

PMID- 16607646
TI  - Association between high voltage overhead transmission lines and mental health: a
      cross-sectional study.
AB  - We examined the association between residential proximity to 60 Hz high voltage
      (22-500 kV) overhead transmission lines (HVOTLs) and mental health (MH). The
      subjects were 223 mothers with a mean age of 37 years. The distance from the
      subject's residence to the closest HVOTL was measured on a map. MH status was
      assessed by the SF-36 Health Survey, which was scored on a 0-100 point scale, and
      an individual with a score of 52 points or less was defined as having poor MH.
      Logistic regression models were used to examine the association between the
      distance from the subjects' residence to the closest HVOTL and MH status. The
      prevalence of poor MH was 15%. Among the 223 subjects, 10 lived within 100 m of a
      HVOTL. The adjusted odds ratios (OR) for poor MH among those who lived 101-300 m
      or within 100 m from HVOTL were 1.29 (95% confidence interval (CI): 0.35-10.13)
      and 1.87 (95% CI: 0.35-10.13), respectively, against the reference category (300+
      m). MH status was not significantly associated with the distance between the
      subject's residence and the closest HVOTL.

PMID- 16607647
TI  - Disseminated Varicella-Zoster virus infection in a girl with T-lineage acute
      lymphoblastic leukemia.

PMID- 16607648
TI  - After prostate cancer: predictors of well-being among long-term prostate cancer
      survivors.
AB  - BACKGROUND: Despite growing numbers of prostate cancer (PCa) survivors, to the
      authors' knowledge there is little research regarding how personality, coping,
      and treatment influence men's psychologic well-being, as distinct from the often
      studied functional, health-related quality of life. The purpose of this study was
      to examine how hope, optimism, use of coping strategies, and primary treatment
      predict well-being, positive and negative affect, impact, depression, and
      adaptive changes among PCa survivors. METHODS: A questionnaire tapping
      personality, primary treatment, and coping strategy predictor variables and
      outcome variables of both positive and negative aspects of well-being was sent to
      1-8-year PCa survivors. The final sample included 490 men. RESULTS: Basic
      univariate analyses demonstrated that the men reported being happy, hopeful, and
      positive, with low levels of negative outcomes. Regression analyses demonstrated
      that positive outcomes were influenced primarily by personality. Negative
      outcomes were found to be affected by both personality and coping strategies.
      Adaptive changes were the only ones found to be significantly affected by primary
      treatment. CONCLUSIONS: Although longer-term survivorship of PCa does not appear
      to be a highly traumatic experience, personality factors and the use of coping
      strategies years after treatment were found to introduce variability to well
      being in complex ways, differing in relation to positive and negative outcomes.
      Clinical attention should be given to how the experience of cancer fits within
      the larger context of an individual's attitudes, choices, and coping strategy
      orientation. Cancer 2006. (c) 2006 American Cancer Society.

PMID- 16607649
TI  - Transfusion independence in patients with myelodysplastic syndromes: impact on
      outcomes and quality of life.
AB  - Anemia is the most common cytopenia associated with myelodysplastic syndromes
      (MDS). Current management relies on frequent red blood cell (RBC) transfusions
      and erythroid growth factors to alleviate symptoms. However, the dependence of
      patients with MDS on repeated RBC transfusions often results in significant
      clinical and economic consequences, poorer outcomes, and diminished health
      related quality of life. In addition, the intensity and duration of RBC
      transfusion dependence can influence responses to treatment after disease
      progression. Erythropoietic growth factors may alleviate the need for RBC
      transfusions in some patients with MDS, although only a minority of patients
      experience responses. Emerging treatment strategies to reduce or eliminate the
      need for RBC transfusions in patients with MDS include immunomodulating drugs,
      immunosuppressive therapy, and differentiating agents. The immunomodulating drug
      lenalidomide in patients who have MDS with 5q deletion is unique among emerging
      approaches, in that cytogenetic remitting activity and durable erythroid
      responses have been achieved. Newer treatments have the potential to improve the
      care of patients with MDS by alleviating the clinical, economic, and quality-of
      life consequences of long-term RBC transfusion dependence.

PMID- 16607650
TI  - Prognostic significance of Wilms tumor gene (WT1) mRNA expression in soft tissue
      sarcoma.
AB  - BACKGROUND: There have been several recent reports that Wilms tumor gene (WT1)
      mRNA is overexpressed in many types of neoplasms, and those results suggested
      that WT1 has oncogenic properties. The objective of the current study was to
      evaluate the prognostic significance of WT1 mRNA expression in patients with soft
      tissue sarcoma. METHODS: Levels of WT1 mRNA expression were examined by
      quantitative, real-time reverse transcriptase-polymerase chain reaction analysis
      in frozen tissue samples from 52 patients with soft tissue sarcoma. Various
      clinicopathologic factors were analyzed along with the disease-specific survival
      rate for correlations with WT1 mRNA expression levels. RESULTS: The levels of WT1
      mRNA expression in a variety of soft tissue sarcomas were significantly greater
      compared with the levels in normal soft tissue samples (P = .0212). No
      significant correlation was observed between the level of WT1 mRNA expression and
      clinicopathologic factors, including gender, age, primary tumor site, tumor
      depth, tumor size, histologic grade, and distant metastasis at initial
      presentation. The disease-specific survival rate for patients with high WT1 mRNA
      expression levels was found significantly poorer compared with the rate for
      patients with low WT1 mRNA expression levels (P = .0182). Moreover, multivariate
      analysis indicated that a high WT1 mRNA expression level was an independent,
      adverse prognostic factor for disease-specific survival (hazards ratio, 2.6; P =
      .0488). CONCLUSIONS: WT1 mRNA expression level can serve as a potent prognostic
      indicator in soft tissue sarcoma patients.

PMID- 16607651
TI  - The clinical impact of histopathologic response assessment by residual tumor cell
      quantification in esophageal squamous cell carcinomas.
AB  - BACKGROUND: The objectives of this study were to investigate histomorphologic
      features as a response classification after neoadjuvant radiochemotherapy
      (RTx/CTx) and to correlate the results with clinical outcome parameters (e.g.,
      postoperative morbidity and mortality, recurrence, and survival) in patients with
      locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Three
      hundred eleven patients with histologically proven, locally advanced,
      intrathoracic ESCC (clinical T3 or T4, N0-N+, M0) located at or above the level
      of the tracheal bifurcation underwent preoperative, combined, simultaneous
      RTx/CTx followed by esophagectomy. Response to RTx/CTx was classified by the
      quantification of residual tumor cells. A histopathologic response was defined as
      <10% residual tumor cells found within the specimen compared with a
      histopathologic nonresponse, which was characterized by >10% residual tumor
      cells. RESULTS: A histopathologic response was correlated significantly with
      complete tumor resection status (R0 resection) (P .0001), histopathologic tumor
      (ypT) category (P <.0001), lymph node involvement (P <.0001), lymphatic vessel
      invasion (P <.001), and survival (P <.0001). A multivariate Cox regression
      analysis revealed that histopathologic response classification according to the
      percentage of residual tumor cells was an independent prognostic factor (P
      <.0001). Nonresponders had greater postoperative pulmonary morbidity (P = .01), a
      greater 30-day mortality rate (P = .02), and a dismal survival rate compared to
      histopathologic responders (P <.0001). CONCLUSIONS: Histopathologic response
      evaluation based on the quantification of residual tumor cells provided
      meaningful information for the assessment of outcomes among patients with ESCC
      who have underwent neoadjuvant RTx/CTx. The current results indicated that
      histopathologic responders may represent a subgroup of patients who benefit from
      neoadjuvant therapy followed by surgery.

PMID- 16607652
TI  - Understanding mechanisms of gamma-globin gene regulation to develop strategies
      for pharmacological fetal hemoglobin induction.
AB  - The developmental regulation of gamma-globin gene expression has shaped research
      efforts to establish therapeutic modalities for individuals affected with sickle
      cell disease (SCD). Fetal hemoglobin (Hb F) synthesis is high at birth, followed
      by a decline to adult levels by 10 months of age. The expression of gamma-globin
      is controlled by a developmentally regulated transcriptional program that is
      recapitulated during normal erythropoiesis in the adult bone marrow. It is known
      that naturally occurring mutations in the gamma-gene promoters cause persistent
      Hb F synthesis after birth, which ameliorates symptoms in SCD by inhibiting
      hemoglobin S polymerization and vaso-occlusion. Several pharmacological agents
      have been identified over the past 2 decades that reactivate gamma-gene
      transcription through different cellular systems. We will review the progress
      made in our understanding of molecular mechanisms that control gamma-globin
      expression and insights gained from Hb F-inducing agents that act through signal
      transduction pathways.

PMID- 16607653
TI  - Morphogenetic adaptation of the looping embryonic heart to altered mechanical
      loads.
AB  - The biophysical mechanisms that drive and regulate cardiac looping are not well
      understood, but mechanical forces likely play a central role. Previous studies
      have shown that cardiac torsion, which defines left-right directionality, is
      caused largely by forces exerted on the heart tube by a membrane called the
      splanchnopleure (SPL). Here we show that, when the SPL is removed from the
      embryonic chick heart, torsion is initially suppressed. Several hours later,
      however, normal torsion is restored. This delayed torsion coincides with
      increased myocardial stiffness, especially on the right side of the heart.
      Exposure to the myosin inhibitor Y-27632 suppressed both responses, suggesting
      that the delayed torsion is caused by an abnormal cytoskeletal contraction. This
      hypothesis is supported further by computational modeling. These results suggest
      that the looping embryonic heart has the ability to adapt to changes in the
      mechanical environment, which may play a regulatory role during morphogenesis.

PMID- 16607654
TI  - fused-somites-like mutants exhibit defects in trunk vessel patterning.
AB  - We identified four mutants in two distinct loci exhibiting similar trunk vascular
      patterning defects in an F3 genetic screen for zebrafish vascular mutants.
      Initial vasculogenesis is not affected in these mutants, with proper
      specification and differentiation of endothelial cells. However, all four display
      severe defects in the growth and patterning of angiogenic vessels in the trunk,
      with ectopic branching and disoriented migration of intersegmental vessels. The
      four mutants are allelic to previously characterized mutants at the fused-somites
      (fss) and beamter (bea) loci, and they exhibit comparable defects in trunk somite
      boundary formation. The fss locus has been shown to correspond to tbx24; we show
      here that bea mutants are defective in the zebrafish dlC gene. Somitic expression
      of known vascular guidance factors efnb2a, sema3a1, and sema3a2 is aberrantly
      patterned in fss and bea mutants, suggesting that the vascular phenotype is due
      to loss of proper guidance cues provided by these factors.

PMID- 16607655
TI  - Closure effects on oxygen transfer and aerobic growth in shake flasks.
AB  - Oxygen mass transfer in shake flasks is an important aspect limiting the culture
      of aerobic microorganisms. In this work, mass transfer of oxygen through a
      closure and headspace of shake flasks is investigated. New equations for
      prediction of kGa in shake flasks with closures are introduced. Using Pseudomonas
      putida, microbial growth on glucose (fast metabolism) and phenol (slow
      metabolism) in shake flasks with closures were studied, considering both
      substrate and oxygen restrictions. A combined model for oxygen mass transfer and
      microbial growth is shown to accurately predict experimental oxygen
      concentrations and oxygen yield factors during growth experiments more accurately
      than previous models.

PMID- 16607657
TI  - Transient performance of two-phase partitioning bioreactors treating a toluene
      contaminated gas stream.
AB  - Two-phase partitioning bioreactors (TPPBs) consist of a cell-containing aqueous
      phase and an immiscible organic phase that sequesters and delivers toxic
      substrates to cells based on equilibrium partitioning. The immiscible organic
      phase, which acts as a buffer for inhibitory substrate loadings, makes it
      possible for TPPBs to handle high volatile organic compound (VOC) loadings, and
      in this study the performance of liquid n-hexadecane and solid styrene butadiene
      (SB) polymer beads used as partitioning phases were compared to a single aqueous
      phase system while treating transient loadings of a toluene contaminated air
      stream by Achromobacter xylosoxidans Y234. The TPPBs operated as well-mixed
      stirred tanks, with total working volumes of 3 L (3 L aqueous for the single
      phase system, 2 L aqueous and 1 L n-hexadecane for the solvent system, and 2.518
      L aqueous volume and 500 g of SB beads for the polymer system). Two 60-min step
      changes (7 and 17 times the nominal loading rates, termed "small" and "large"
      steps, respectively) were imposed on the systems and the performance was
      characterized by the overall removal efficiencies, instantaneous removal
      efficiency recovery times (above 95% removal), and dissolved oxygen recovery
      times. For the small steps, with a nominal loading of 343 g/m3/h increasing to
      2,400 g/m3/h, the TPPB system using n-hexadecane as the second phase performed
      best, removing 97% of the toluene fed to the system compared with 90% for the
      polymer beads system and only 69% for the single-phase system. The imposed large
      transient gave similar results, although the impact of the presence of a second
      sequestering phase was more pronounced, with the n-hexadecane system maintaining
      much reduced aqueous toluene concentrations leading to significantly improved
      performance. This investigation also showed that the presence of both n
      hexadecane and SB beads improved the oxygen transfer within the systems.

PMID- 16607656
TI  - Isolation and analysis of a baculovirus vector that supports recombinant
      glycoprotein sialylation by SfSWT-1 cells cultured in serum-free medium.
AB  - The inability to sialylate recombinant glycoproteins is a critical limitation of
      the baculovirus-insect cell expression system. This limitation is due, at least
      in part, to the absence of detectable sialyltransferase activities and CMP-sialic
      acids in the insect cell lines routinely used as hosts in this system. SfSWT-1 is
      a transgenic insect cell line encoding five mammalian glycosyltransferases,
      including sialyltransferases, which can contribute to sialylation of recombinant
      glycoproteins expressed by baculovirus vectors. However, sialylation of
      recombinant glycoproteins requires culturing SfSWT-1 cells in the presence of
      fetal bovine serum or another exogenous source of sialic acid. To eliminate this
      requirement and extend the utility of SfSWT-1 cells, we have isolated a new
      baculovirus vector, AcSWT-7B, designed to express two mammalian enzymes that can
      convert N-acetylmannosamine to CMP-sialic acid during the early phase of
      infection. AcSWT-7B was also designed to express a model recombinant glycoprotein
      during the very late phase of infection. Characterization of this new baculovirus
      vector showed that it induced high levels of intracellular CMP-sialic acid and
      sialylation of the recombinant N-glycoprotein upon infection of SfSWT-1 cells
      cultured in serum-free medium supplemented with N-acetylmannosamine. In addition,
      co-infection of SfSWT-1 cells with AcSWT-7B plus a conventional baculovirus
      vector encoding human tissue plasminogen activator resulted in sialylation of
      this recombinant N-glycoprotein under the same culture conditions. These results
      demonstrate that AcSWT-7B can be used in two different ways to support
      recombinant N-glycoprotein sialylation by SfSWT-1 cells in serum-free medium.
      Thus, AcSWT-7B can be used to extend the utility of this previously described
      transgenic insect cell line for recombinant sialoglycoprotein production.

PMID- 16607658
TI  - A kinetic model to explain the maximum in alpha-amylase activity measurements in
      the presence of small carbohydrates.
AB  - The effect of the presence of several small carbohydrates on the measurement of
      the alpha-amylase activity was determined over a broad concentration range. At
      low carbohydrate concentrations, a distinct maximum in the alpha-amylase activity
      versus concentration curves was observed in several cases. At higher
      concentrations, all carbohydrates show a decreasing alpha-amylase activity at
      increasing carbohydrate concentrations. A general kinetic model has been
      developed that can be used to describe and explain these phenomena. This model is
      based on the formation of a carbohydrate-enzyme complex that remains active. It
      is assumed that this complex is formed when a carbohydrate binds to alpha-amylase
      without blocking the catalytic site and its surrounding subsites. Furthermore,
      the kinetic model incorporates substrate inhibition and substrate competition.
      Depending on the carbohydrate type and concentration, the measured alpha-amylase
      activity can be 75% lower than the actual alpha-amylase activity. The model that
      has been developed can be used to correct for these effects in order to obtain
      the actual amount of active enzyme.

PMID- 16607659
TI  - Induced-fit recognition of DNA by small circular oligonucleotides.
AB  - We have investigated the molecular interaction between cyclic and linear
      oligonucleotides. We have found that short cyclic oligonucleotides can induce
      hairpinlike structures in linear DNA fragments. By using NMR and CD spectroscopy
      we have studied the interaction of the cyclic oligonucleotide d<pCCTTCGGT> with
      d<pCAGTCCCT>, as well as with its two linear analogs d(GTCCCTCA) and d(CTCAGTCC).
      Here we report the NMR structural study of these complexes. Recognition between
      these oligonucleotides occurs through formation of four intermolecular Watson
      Crick base pairs. The three-dimensional structure is stabilized by two tetrads,
      formed by facing the minor-groove side of the Watson-Crick base pairs. Overall,
      the structure is similar to those observed previously in other quadruplexes
      formed by minor-groove alignment of Watson-Crick base pairs. However, in this
      case the complexes are heterodimeric and are formed by two different tetrads
      (G:C:A:T and G:C:G:C). These complexes represent a new model of DNA recognition
      by small cyclic oligonucleotides, increasing the number of potential applications
      of these interesting molecules.

PMID- 16607660
TI  - Acetylene decomposition on Rh(100): theory and experiment.
AB  - The decomposition of acetylene on a Rh(100) single crystal was studied by a
      combination of experimental techniques [static secondary ion mass spectrometry
      (SSIMS), temperature-programmed desorption (TPD), and low-energy electron
      diffraction (LEED)] to gain insight into the reaction pathway and the nature of
      the reaction intermediates. The experimental techniques were combined with a
      computational approach using density functional theory (DFT). Acetylene adsorbs
      irreversibly on the Rh(100) surface and eventually decomposes to atomic carbon
      and gas-phase hydrogen. The combination of experimental and computational results
      enabled us to determine the most likely reaction pathway for the decomposition
      process.

PMID- 16607661
TI  - Dynamic light-scattering analysis of the electrostatic interaction of
      hexahistidine-tagged cytochrome P450 enzyme with semiconductor quantum dots.
AB  - Currently, there is great interest in the development of methods suitable for
      determining the stoichiometry of biomolecules attached to nanoparticles. We
      describe the use of the dynamic light-scattering technique (DLS) to determine the
      stoichiometry of the protein cytochrome P450(BSbeta) attached to CdS and CdSe
      quantum dots (QDs). The enzyme-conjugated QDs have different diffusion
      characteristics compared to the QD and enzyme precursors, expressed in their
      size, scattering intensity as well as zeta-potential values. The significant
      enhancement of the scattering intensity of QDs observed upon conjugation with the
      P450(BSbeta) due to the refractive-index increment and the systematic variation
      in zeta potential resulting from charge neutralization of the anionic QDs by the
      cationic histidine-tagged P450(BSbeta) have been used for stoichiometry
      determination.

PMID- 16607662
TI  - Hydrogen electrocatalysis.
AB  - A selection of recent theoretical and experimental studies on electrolytic
      hydrogen evolution is presented. It is demonstrated with well-defined model
      surfaces that this reaction is a very structure-sensitive process.
      Crystallographic orientation, defect density and surface composition are
      parameters that determine the local geometric and electronic surface structure,
      and are thus crucial for the electrocatalytic activity as characterised by the
      exchange current density. The observed trends can be understood within a recent
      theory by J. K. Norskov et al., which is based on density functional calculations
      and which emphasises the impact of hydrogen chemisorption energies on the
      reaction rate, that is, on the exchange current density. The particular
      electrocatalytic activities of ultrathin metal films and of nanostructures are
      addressed.

PMID- 16607663
TI  - Feature multiplexing--improving the efficiency of microarray devices.

PMID- 16607664
TI  - Regulating supramolecular function in membranes: calixarenes that enable or
      inhibit transmembrane Cl- transport.

PMID- 16607665
TI  - Heck coupling with nonactivated alkenyl tosylates and phosphates: examples of
      effective 1,2-migrations of the alkenyl palladium(II) intermediates.

PMID- 16607666
TI  - A sodalite-like framework based on octacyanomolybdate and neodymium with guest
      methanol molecules and neodymium octahydrate ions.

PMID- 16607667
TI  - Post-translational covalent labeling reveals heterogeneous mobility of individual
      G protein-coupled receptors in living cells.

PMID- 16607668
TI  - The activation of electrophile, nucleophile and leaving group during the reaction
      catalysed by pI258 arsenate reductase.
AB  - The reduction of arsenate to arsenite by pI258 arsenate reductase (ArsC) combines
      a nucleophilic displacement reaction with a unique intramolecular disulfide
      cascade. Within this reaction mechanism, the oxidative equivalents are
      translocated from the active site to the surface of ArsC. The first reaction step
      in the reduction of arsenate by pI258 ArsC consists of a nucleophilic
      displacement reaction carried out by Cys10 on dianionic arsenate. The second step
      involves the nucleophilic attack of Cys82 on the Cys10-arseno intermediate formed
      during the first reaction step. The onset of the second step is studied here by
      using quantum chemical calculations in a density functional theory context. The
      optimised geometry of the Cys10-arseno adduct in the ArsC catalytic site
      (sequence motif: Cys10-Thr11-Gly12-Asn13-Ser14-Cys15-Arg16-Ser17) forms the
      starting point for all subsequent calculations. Thermodynamic data and a hard and
      soft acids and bases (HSAB) reactivity analysis show a preferential nucleophilic
      attack on a monoanionic Cys10-arseno adduct, which is stabilised by Ser17. The P
      loop active site of pI258 ArsC activates first a hydroxy group and subsequently
      arsenite as the leaving group, as is clear from an increase in the calculated
      nucleofugality of these groups upon going from the gas phase to the solvent phase
      to the enzymatic environment. Furthermore, the enzymatic environment stabilises
      the thiolate form of the nucleophile Cys82 by 3.3 pH units through the presence
      of the eight-residue alpha helix flanked by Cys82 and Cys89 (redox helix) and
      through a hydrogen bond with Thr11. The importance of Thr11 in the pKa regulation
      of Cys82 was confirmed by the observed decrease in the kcat value of the Thr11Ala
      mutant as compared to that of wild-type ArsC. During the final reaction step,
      Cys89 is activated as a nucleophile by structural alterations of the redox helix
      that functions as a pKa control switch for Cys89; this final step is necessary to
      expose a Cys82-Cys89 disulfide.

PMID- 16607669
TI  - C-terminal fluorescence labeling of proteins for interaction studies on the
      single-molecule level.

PMID- 16607670
TI  - Synthesis of Neu5Ac oligosaccharides and analogues by transglycosylation and
      their binding properties as ligands to MAG.

PMID- 16607671
TI  - Novel aza peptide inhibitors and active-site probes of papain-family cysteine
      proteases.
AB  - Recent characterization of multiple classes of functionalized azapeptides as
      effective covalent inhibitors of cysteine proteases prompted us to investigate O
      acyl hydroxamates and their azapeptide analogues for use as activity-based probes
      (ABPs). We report here a new class of azaglycine-containing O-acylhydroxamates
      that form stable covalent adducts with target proteases. This allows them to be
      used as ABPs for papain family cysteine proteases. A second class of related
      analogues containing a novel O-acyl hydroxyurea warhead was found to function as
      covalent inhibitors of papain-like proteases. These inhibitors can be easily
      synthesized on solid support, which allows rapid optimization of compounds with
      improved selectivity and potency for a given target enzyme. We present here one
      such optimized inhibitor that showed selective inhibition of falcipain 1, a
      protease of the malaria-causing parasite, Plasmodium falciparum.

PMID- 16607672
TI  - Intramolecular triplet energy transfer in donor-acceptor molecules linked by a
      crown ether bridge.
AB  - Bichromophoric compounds BP-C-NP and BP-C-NBD were synthesized with benzophenone
      chromophore (BP) as the donor, and 2-naphthyl (NP) and norbornadiene group (NBD)
      as the acceptor, respectively. Their intramolecular triplet energy transfer was
      examined. The bridges linking the donor and acceptors in these molecules involve
      a crown ether moiety complexing a sodium ion. Phosphorescence quenching, flash
      photolysis and photosensitized isomerization experiments indicate that
      intramolecular triplet energy transfer occurs with rate constants of about 3.3 x
      10(5) and 4.8 x 10(5) s(-1) and efficiencies of about 33 and 42 % for BP-C-NP and
      BP-C-NBD, respectively. Theoretical calculations indicate that these molecules
      adopt conformations below room temperature which allow their two-end chromophores
      conducive to through-space energy transfer.

PMID- 16607673
TI  - Structure determination of ursene-type triterpenes by NMR techniques.
AB  - Two new ursene-type triterpenes, nudicauline A and nudicauline B, have been
      isolated from Launaea nudicaulis. Their structures have been assigned as 3beta
      hydroxy-urs-11-ene (1) and 3beta-acetyl-urs-11-ene (2), respectively, by
      extensive NMR studies. In addition, olean-11,13(18)-diene (3), 3beta-hydroxy
      13(28)-epoxy-urs-11-ene (4) and 3-keto-13(28)-epoxy-urs-11-ene (5) are also
      reported for the first time from this species.

PMID- 16607674
TI  - Complete assignments of 1H and 13C NMR spectral data for a novel diterpenoid from
      Semiaquilegia adoxoides.
AB  - Semiaquilegoside A (1), a new diterpenoid, was isolated from the roots of
      Semiaquilegia adoxoides. Its chemical structure was established as 3beta, 11-
      dihydroxy-12-O-beta-D-glucopyranosyl-8,11,13-abietatrien-6-one through
      spectroscopic techniques and chemical analysis.

PMID- 16607675
TI  - Nonempirical calculations of NMR indirect spin-spin coupling constants. Part 15:
      pyrrolylpyridines.
AB  - Conformational study of 2-(2-pyrrolyl)pyridine and 2,6-di(2-pyrrolyl)pyridine was
      performed on the basis of the experimental measurements and high-level ab initio
      calculations of the one-bond 13C-13C, 13C-1H and 15N-1H spin-spin coupling
      constants showing marked stereochemical behavior upon the internal rotation
      around the pyrrole-pyridine interheterocyclic bonds. Both compounds were
      established to adopt predominant s-cis conformations with no noticeable out-of
      plane deviations.

PMID- 16607677
TI  - Molecular biology of squamous cell carcinoma of the anus.
AB  - BACKGROUND: Squamous cell carcinoma of the anal canal provides a model for
      studying the contribution of human papillomavirus (HPV) and human
      immunodeficiency virus (HIV) infection to the development of neoplasia. This
      paper reviews the existing literature relating to the molecular biology of anal
      squamous cell carcinoma and proposes a theory of pathogenesis. METHODS: A Medline
      literature search was performed to identify English articles on the pathogenesis
      of squamous cell carcinoma of the anus; further articles were obtained from the
      references quoted in the literature initially reviewed. RESULTS: HPV infection
      and subsequent HPV DNA integration are necessary, but not sufficient, to cause
      cancer progression. Loss of heterozygosity at 11q23 is the most consistent
      genomic change observed. Loss of heterozygosity at 17p, 18q and 5q is frequently
      observed in tumours of HIV-negative patients, but not in those of HIV-positive
      patients. Current data suggest that mutations in p53, DCC and APC tumour
      suppressor genes contribute to the stepwise progression of anal squamous cell
      carcinoma in immunocompetent individuals. CONCLUSION: In comparison with
      immunocompetent individuals, HIV-positive patients have persistent HPV infection
      in the anal canal. In this population, microsatellite instability, rather than
      chromosomal instability, appears to be a preferred pathway for rapid progression
      towards invasive carcinoma.

PMID- 16607678
TI  - Randomized clinical trial of splenectomy versus splenic preservation in patients
      with proximal gastric cancer.
AB  - BACKGROUND: Preservation or removal of the spleen during total gastrectomy for
      proximal gastric cancer is a matter of debate. METHODS: A randomized clinical
      trial included patients with gastric adenocarcinoma who underwent total
      gastrectomy either with (104 patients) or without (103) splenectomy.
      Postoperative outcome in the two groups was compared, including morbidity,
      mortality and survival. RESULTS: Gastrectomy combined with splenectomy tended to
      be associated with slightly higher morbidity and mortality rates, a slightly
      greater incidence of lymph node metastasis at the splenic hilum and along the
      splenic artery, and marginally better survival, but there were no statistically
      significant differences between the groups. Splenectomy had no impact on survival
      in patients with metastatic lymph nodes at the hilum of the spleen or in those
      with metastatic lymph nodes along the splenic artery. CONCLUSION: These results
      do not support the use of prophylactic splenectomy to remove macroscopically
      negative lymph nodes near the spleen in patients undergoing total gastrectomy for
      proximal gastric cancer.

PMID- 16607679
TI  - Long-term outcome of resection of large hepatocellular carcinoma.
AB  - BACKGROUND: The role of hepatectomy in the treatment of large hepatocellular
      carcinoma (HCC) is still controversial. This retrospective study evaluated
      whether the long-term outcome of hepatectomy for large HCC improved over 14 years
      in one centre. METHODS: Data from 2102 patients who underwent hepatectomy for
      large HCC were collected prospectively and divided into two time intervals for
      analysis: before end of December 1996 (group 1) and after December 1996 (group
      2). Clinicopathological data for the two groups were compared, and factors
      associated with long-term prognosis were further analysed. RESULTS: Cumulative 1
      , 3- and 5-year overall survival rates were 71.2, 58.8 and 38.7 per cent
      respectively in group 2, and were significantly better than respective rates of
      67.8, 50.7 and 27.9 per cent in group 1. Cumulative 1-, 3- and 5-year disease
      free survival rates were 61.5, 38.6 and 23.8 per cent respectively in group 2,
      and 56.5, 34.7 and 18.9 per cent in group 1. There was a significant difference
      in median survival time after recurrence between groups 2 and 1 (17 and 10 months
      respectively; P = 0.043). CONCLUSION: Hepatic resection in patients with large
      HCC has improved overall and disease-free survival during the past decade at this
      institute. Long-term survival can be improved significantly by aggressive
      treatment of recurrent tumours.

PMID- 16607680
TI  - Improved quality of life after sympathetic block for upper limb hyperhidrosis.
AB  - BACKGROUND: The aim of the study was to assess two disease-specific quality of
      life (QoL) instruments after limited endoscopic thoracic sympathetic block (TS)
      at T4 for upper limb hyperhidrosis. METHODS: : Between 2001 and 2005, 112
      patients underwent 223 TS procedures in a prospective study. Some 103 patients
      (92.0 per cent) had palmar, 87 (77.7 per cent) had axillary and 75 (67.0 per
      cent) had combined hyperhidrosis. QoL questionnaires devised by Keller et al. and
      Milanez de Campos et al. were employed before and after treatment. Mean(s.d.)
      follow-up was 21.9(10.1) months. RESULTS: A total of 106 patients (94.6 per cent)
      were evaluated. All patients with palmar hyperhidrosis were completely or almost
      dry after surgery. Side-effects of compensatory sweating and gustatory sweating
      were observed in 17.0 and 28.3 per cent of patients respectively. QoL improved
      after TS in 100 per cent (Keller) and 97.3 per cent (Milanez de Campos) of
      patients illustrated by ameliorated scores of 78.7 and 67.8 per cent,
      respectively (both P < 0.001). Both questionnaires showed that compensatory
      sweating resulted in reduced postoperative QoL (P = 0.011, Keller; P = 0.032,
      Milanez de Campos). CONCLUSION: Endoscopic sympathetic block at T4 leads to
      improved QoL. Both current questionnaires fulfilled validation criteria for
      disease-specific QoL instruments in upper limb hyperhidrosis.

PMID- 16607681
TI  - Surgery in developing nations.

PMID- 16607683
TI  - Disturbances of the microcirculation in acute pancreatitis.
AB  - BACKGROUND: Severe acute pancreatitis is characterized by pancreatic necrosis,
      resulting in local and systemic inflammation. Pancreatitis affects both the
      systemic and pancreatic vasculature. This review focuses on the underlying
      processes involved in the changes of microvascular anatomy following acute
      pancreatitis. METHODS: A Medline/PubMed search (January 1966 to December 2005)
      with manual cross-referencing was conducted. All relevant articles investigating
      the pancreatic microcirculatory anatomy and the effect of pancreatitis on the
      microcirculation were included. RESULTS: The pancreas is susceptible to ischaemic
      insult, which can exacerbate acute pancreatitis. There is also increasing
      evidence of pancreatic and systemic microvascular disturbances in the
      pathogenesis of pancreatitis, including vasoconstriction, shunting, inadequate
      perfusion, and increased blood viscosity and coagulation. These processes may be
      caused or exacerbated by ischaemia-reperfusion injury and the development of
      oxygen-derived free radicals. CONCLUSION: Acute pancreatitis impairs the
      pancreatic and systemic microcirculation, which is a key pathological process in
      the development of severe necrotizing disease.

PMID- 16607682
TI  - Survival benefit of high ligation of the inferior mesenteric artery in sigmoid
      colon or rectal cancer surgery.
AB  - BACKGROUND: The aim of this study was to assess the impact of inferior mesenteric
      artery (IMA) root nodal dissection before high ligation of the artery on survival
      in patients with sigmoid colon or rectal cancer. METHODS: Data on 1188
      consecutive patients who underwent resection for sigmoid colon or rectal cancer,
      with high ligation of the IMA, were identified from a prospective database (April
      1965 to December 1999). Survival of patients with involvement of nodes along the
      IMA proximal to the origin of the left colic artery (root nodes, station 253)
      through the bifurcation of the superior rectal artery (trunk nodes, station 252)
      was determined. RESULTS: Twenty patients (1.7 per cent) had metastatic
      involvement of station 253 lymph nodes and 99 (8.3 per cent) had metastases to
      station 252. The 5- and 10-year survival rates of patients with metastases to
      station 253 were 40 and 21 per cent, and those for patients with metastases to
      station 252 were 50 and 35 per cent, respectively. CONCLUSION: High ligation of
      the IMA allows curative resection and long-term survival in patients with cancer
      of the sigmoid colon or rectum and nodal metastases at the origin of the IMA.

PMID- 16607684
TI  - Comparative study of left colonic Peritonitis Severity Score and Mannheim
      Peritonitis Index.
AB  - BACKGROUND: Prognostic evaluation of patients with left colonic perforation is
      useful in predicting mortality. The aims of this prospective study were to
      determine the prognostic value of the left colonic Peritonitis Severity Score
      (PSS) and to compare it with the Mannheim Peritonitis Index (MPI). METHODS: One
      hundred and fifty-six patients underwent emergency operation for distal colonic
      peritonitis. The PSS and MPI were calculated for each patient. The Spearman rank
      correlation coefficient was used to measure the association between the two
      scores. The predictive power of the two scoring systems and their differences
      were studied using the area under the receiver-operator characteristic (ROC)
      curve. RESULTS: Forty-one patients died (26.3 per cent). The relationship between
      scores and mortality was statistically significant for each scoring system (P <
      0.001). The Spearman rank correlation coefficient for the correlation between the
      MPI and PSS was 0.55 (P < 0.001). There was no difference between areas under the
      ROC curves for the two systems. CONCLUSION: The PSS and MPI are both well
      validated scoring systems for left colonic peritonitis. Their routine use might
      allow stratification of patients according to mortality risk.

PMID- 16607685
TI  - Radiological staging of gastrointestinal and breast tumours.

PMID- 16607686
TI  - Meta-analysis of colonic reservoirs versus straight coloanal anastomosis after
      anterior resection (Br J Surg 2006; 93: 19-32).

PMID- 16607688
TI  - Randomized clinical trial of day-care versus overnight-stay laparoscopic
      cholecystectomy (Br J Surg 2006; 93: 40-45).

PMID- 16607689
TI  - Bile duct injury in the era of laparoscopic cholecystectomy (Br J Surg 2006; 93:
      158-168).

PMID- 16607691
TI  - Minimally invasive surgery of the thyroid and parathyroid glands (Br J Surg 2006;
      93: 1-2).

PMID- 16607692
TI  - A risk index for early node-negative breast cancer.
AB  - BACKGROUND: This study compared the application of the St Gallen 2001
      classification with a risk index developed at the New South Wales Breast Cancer
      Institute (BCI Index) for women with node-negative breast cancer treated without
      adjuvant systemic therapy. METHODS: The BCI risk categories were constructed by
      identifying combinations of prognostic indicators that produced homogeneous low-,
      intermediate- and high-risk groups using the same variables as in the St Gallen
      classification. RESULTS: The BCI low-risk category consisted of women aged 35
      years or more with a grade 1 oestrogen receptor (ER)-positive tumour 20 mm or
      less in diameter, or with a grade 2 ER-positive tumour of 15 mm or less. This
      category constituted 40.1 per cent of patients, with a 10-year distant relapse
      free survival (DRFS) rate of 97.2 per cent. The BCI intermediate-risk category
      included women aged 35 years or more with a grade 2 ER-positive tumour of
      diameter 16-20 mm, or a grade 1 or 2 ER-negative tumour measuring 15 mm or less,
      and comprised 12.1 per cent of the women, with a 10-year DRFS rate of 88 per
      cent. The high-risk category comprised 47.7 per cent of women, with a 10-year
      DRFS rate of 68.4 per cent. CONCLUSION: If confirmed in other data sets, the BCI
      Index may be used to identify women at low risk of distant relapse (2.8 per cent
      at 10 years) who are unlikely to benefit from adjuvant systemic therapy, and
      women at intermediate risk of distant relapse (12 per cent at 10 years) in whom
      the benefit of adjuvant systemic therapy is small.

PMID- 16607693
TI  - The prevalence of thrombophilia in patients with symptomatic peripheral vascular
      disease.
AB  - BACKGROUND: The aim of this prospective study was to establish the prevalence of
      thrombophilia and hyperhomocysteinaemia using a comprehensive screen in patients
      with peripheral vascular disease. METHODS: A total of 150 patients with
      peripheral vascular disease (with an ankle brachial pressure index of less than
      0.8) underwent thrombophilia screening (protein C and protein S, antithrombin,
      lupus anticoagulant, activated protein C resistance and factor V Leiden and
      prothrombin mutations). Fasting homocysteine assays were also performed. RESULTS:
      A thrombophilia defect was found in 41 patients (27.3 per cent). The commonest
      was protein S deficiency, found in 17 patients (11.3 per cent). Others included
      factor V Leiden mutation, found in 10 (6.7 per cent) and protein C deficiency,
      found in six (4.0 per cent). Lupus anticoagulant and prothrombin mutation were
      both found in six (4.0 per cent). One patient had an antithrombin deficiency.
      Only the presence of critical ischaemia was associated with a positive
      thrombophilia screen on single variable analysis (P = 0.03).
      Hyperhomocysteinaemia was present in over a third of the study group (37.3 per
      cent): 45 defined as moderate and 11 as intermediate. CONCLUSION: A quarter of
      patients with peripheral vascular disease had evidence of thrombophilia, and a
      third had hyperhomocysteinaemia.

PMID- 16607694
TI  - Chemistry's green revolution.

PMID- 16607695
TI  - Interferon alfa, peginterferon alfa and retinopathy.
AB  - (1) Retinal damage is a known adverse effect of interferon alfa. (2) Similar
      adverse effects have been reported with pegylated interferon alfa. The disorders
      generally regress within a few months, despite continued treatment.

PMID- 16607696
TI  - Phytoestrogens and endometrial hyperplasia.
AB  - (1) Short-term clinical trials have shown that soy phytoestrogens have a slight
      preventive effect on hot flushes. However, this finding is based on a low level
      of evidence. (2) A double-blind placebo-controlled trial involving about 300
      women and lasting 5 years showed that phytoestrogens were associated with an
      increase in the incidence of endometrial hyperplasia (3.8% versus 0%). (3) In
      practice, the risk-benefit ratio of phytoestrogens has not been adequately
      assessed. Their effect on the endometrium, and the many unknowns concerning the
      risk of thromboembolism and breast cancer, may offset the modest effect of
      phytoestrogens on hot flushes.

PMID- 16607697
TI  - The pancreatic islet endothelial cell: emerging roles in islet function and
      disease.
AB  - The pancreatic islets are one of the most vascularized organs of the body. This
      likely reflects the requirements of the organ for a rich supply of nutrients and
      oxygen to the tissue, as well as the need for rapid disposal of metabolites and
      secreted hormones. The islet endothelium is richly fenestrated to facilitate
      trans-endothelial transport of secreted hormones, has a unique expression of
      surface markers, and produces a number of vasoactive substances and growth
      factors. The islet endothelial cells play a critical role in the early phase of
      type 1 diabetes mellitus by increasing the expression of surface leucocyte-homing
      receptors, thereby enabling immune cells to enter the endocrine tissue and cause
      beta-cell destruction. Following transplantation, pancreatic islets lack a
      functional capillary system and need to be properly revascularized. Insufficient
      revascularization may severely affect the transport properties of the islet
      endothelial system, resulting in a dysfunctional islet graft.

PMID- 16607698
TI  - Islet neogenesis: a potential therapeutic tool in type 1 diabetes.
AB  - Current therapies for type 1 diabetes, including fastidious blood glucose
      monitoring and multiple daily insulin injections, are not sufficient to prevent
      complications of the disease. Though pancreas and possibly islet transplantation
      can prevent the progression of complications, the scarcity of donor organs limits
      widespread application of these approaches. Understanding the mechanisms of beta
      cell mass expansion as well as the means to exploit these pathways has enabled
      researchers to develop new strategies to expand and maintain islet cell mass.
      Potential new therapeutic avenues include ex vivo islet expansion and improved
      viability of islets prior to implantation, as well as the endogenous expansion of
      beta-cell mass within the diabetic patient. Islet neogenesis, through stem cell
      activation and/or transdifferentiation of mature fully differentiated cells, has
      been proposed as a means of beta-cell mass expansion. Finally, any successful new
      therapy for type 1 diabetes via beta-cell mass expansion will require prevention
      of beta-cell death and maintenance of long-term endocrine function.

PMID- 16607699
TI  - Role of oxidative stress, endoplasmic reticulum stress, and c-Jun N-terminal
      kinase in pancreatic beta-cell dysfunction and insulin resistance.
AB  - Type 2 diabetes is the most prevalent and serious metabolic disease affecting
      people all over the world. Pancreatic beta-cell dysfunction and insulin
      resistance are the hallmark of type 2 diabetes. Normal beta-cells can compensate
      for insulin resistance by increasing insulin secretion and/or beta-cell mass, but
      insufficient compensation leads to the onset of glucose intolerance. Once
      hyperglycemia becomes apparent, beta-cell function gradually deteriorates and
      insulin resistance aggravates. Under diabetic conditions, oxidative stress and
      endoplasmic reticulum stress are induced in various tissues, leading to
      activation of the c-Jun N-terminal kinase pathway. The activation of c-Jun N
      terminal kinase suppresses insulin biosynthesis and interferes with insulin
      action. Indeed, suppression of c-Jun N-terminal kinase in diabetic mice improves
      insulin resistance and ameliorates glucose tolerance. Thus, the c-Jun N-terminal
      kinase pathway plays a central role in pathogenesis of type 2 diabetes and could
      be a potential target for diabetes therapy.

PMID- 16607702
TI  - Six degrees of separation. Interview by Barbara C Zeiger.

PMID- 16607701
TI  - Nursing home transition.

PMID- 16607703
TI  - Medicaid and community services for developmental disabilities.

PMID- 16607704
TI  - A woman from British Guyana with recurrent back pain and fever. Chyluria
      associated with infection due to Wuchereria bancrofti.

PMID- 16607705
TI  - The impact of welfare reform on health insurance coverage in rural areas.

PMID- 16607706
TI  - Why are health care expenditures increasing and is there a rural differential?

PMID- 16607707
TI  - Hope and the ethics of disclosure for terminally ill cancer patients.
AB  - Cancer diagnosis presents a disclosure dilemma for physicians, holding in tension
      the physician's obligation to provide diagnosis and its impact on the patient. To
      address this dilemma the traditional approach of physicians, typified as the
      psychological-empirical approach to hope, needs to be complemented by a patient
      oriented approach, described as the phenomenological hermeneutics of hope.

PMID- 16607708
TI  - Institutional review boards (IRBs) and working with adverse event reports.

PMID- 16607709
TI  - Research subject complains about how she was treated by an institutional review
      board (IRB).

PMID- 16607710
TI  - Plaintiffs claim that research subject was too drowsy to give informed consent.

PMID- 16607711
TI  - Confidentiality and duty to warn the third parties in HIV/AIDS context.
AB  - Generally, physicians have a legal and ethical obligation of keeping
      confidentiality regarding their communications with patients. So, the most
      complicated ethical and legal questions arise when the HIV-infected person
      deliberately avoids to report to the interested individuals about the possibility
      of HIV transmission. The decisive factor, which emphasizes the need of such a
      discussion about confidentiality in HIV cases, is the character of the HIV: HIV
      is incurable, causes the danger of fatal outcome, discrimination etc. The aim of
      the paper is to explore the limits of confidentiality, as there is a duty to warn
      the third party about the danger of HIV transmission in that case on the part of
      the physician, even when the HIV-infected individual categorically refuses doing
      so. The paper analyses some specificities of confidentiality keeping in HIV
      pandemia, the responsibilities of a physician concerning the third party and his
      duty to warn him/her. Special attention is paid to those cases, when the fact of
      HIV infection has to be reported upon the patient's death or when the disclosure
      of the confidential information is connected with the possibility to start the
      post-exposure prophylactics. The paper presumes that confidentiality is not an
      absolute value, when there exists a real danger to the third party (e.g. a
      spouse, a care-taking relative, a victim).

PMID- 16607712
TI  - Training and dissemination of good practices for research ethics committees:
      standardization, harmonization and collaboration.

PMID- 16607713
TI  - Activities of the Central Ethics Committee of the Ministry of Health of the
      Slovak Republic.

PMID- 16607714
TI  - Ethics support in clinical practice in Europe--situation overview.

PMID- 16607715
TI  - Current ethical dilemmas in clinical practice in Europe.
AB  - The need for clinical ethics support is increasingly recognised by clinicians and
      health services across Europe, and many countries already have clinical ethics
      committees. The range of ethical issues for which clinicians may require support
      is likely to show some similarity across countries, but differences in the
      frequency and type of ethical issue will also be seen, related to cultural,
      economic, and systematic differences between countries. In this paper I consider
      some of the common ethical issues faced by clinicians, drawing on my knowledge
      and experience of the UK situation, and informed by discussions with other
      European colleagues. I consider some specific examples to illustrate general
      issues, and suggest some possible areas of difference that will be important in
      addressing clinical ethics support in a European wide context.

PMID- 16607716
TI  - Clinical ethics support services in Europe.
AB  - The paper presents the main debates that have taken place on clinical ethics
      committees within the European project entitled Ethical Function in Hospital
      Ethics Committees. It depicts the great variety of formula existing in Europe in
      terms of legal status, functions, accessibility, composition and training
      requirements and a the onset of clinical ethics concept itself. Moreover, in the
      interstices of the various institutionalised ethics systems we can find extremely
      innovative initiatives under development, spawned more by premises of a political
      nature than drawn from the specialised corps of medical ethics. Could clinical
      ethical committees play some role in the overall democratisation process in
      medicine?

PMID- 16607717
TI  - The challenges for clinical ethics education in Europe.
AB  - The experiences of bioethics education tend to be provided at three levels. At
      undergraduate level a more general approach to bioethics is offered that may
      include both medical and non-medical students. Post graduate education may be
      formal, usually at advanced degree of doctorate level, or part of continuing
      professional development, either in the form of a course in clinical bioethics or
      through experienced gained by sitting on a clinical ethics committee. Two of
      these postgraduate approaches--a Masters programme in bioethics and the
      experience gained in developing a Hospital based bioethics programme--are
      considered in more detail in this presentation.

PMID- 16607718
TI  - Ethics support in clinical practice in Europe: Albania.

PMID- 16607719
TI  - Ethics support in clinical practice in Europe: Armenia.

PMID- 16607720
TI  - Ethics support in clinical practice in Europe: Croatia.

PMID- 16607721
TI  - Ethics support in clinical practice in Europe: Cyprus.

PMID- 16607722
TI  - Ethics support in clinical practice in Europe: Estonia.

PMID- 16607723
TI  - Ethics committees in Greece.

PMID- 16607724
TI  - Ethics support in clinical practice in Europe: Lithuania.

PMID- 16607725
TI  - Ethics support in clinical practice in Europe: Romania.

PMID- 16607726
TI  - Ethics support in clinical practice in Europe: Russian Federation.

PMID- 16607727
TI  - Ethics support in clinical practice in Europe: Serbia and Montenegro.

PMID- 16607728
TI  - Ethics support in clinical practice in Europe: Slovenia.

PMID- 16607729
TI  - Ethics support in clinical practice in Europe: Slovak Republic.

PMID- 16607730
TI  - Ethics support in clinical practice in Europe: Macedonia.

PMID- 16607731
TI  - Ethics support in clinical practice in Europe: Turkey.

PMID- 16607733
TI  - Chemoprevention for Barrett's esophagus: first the good news.

PMID- 16607732
TI  - Ethics support in clinical practice in Europe: Ukraine.

PMID- 16607734
TI  - [Radioisotopes for the evaluation of pulmonary capillary permeability in ARDS].
AB  - The dysfunction of pulmonary capillary represents the marker of Acute Respiratory
      Distress Syndrome (ARDS). Each current mean of investigation in ARDS
      (radiography, CT, ultrasonography, double dilution technique, electric impedance,
      bronchoscopy) has its downfalls and has not succeeded in becoming a gold standard
      in evaluation of this pathology. The development of any treatment is hampered by
      the lack of a rapid and objective method of evaluation of the progress of the
      disease. The radioisotopic evaluation of pulmonary capillary permeability
      realizes a picture of a physiologic process blood-interstitial exchange at
      pulmonary level. The most recent studies appear to suggest that this method of
      investigation can objectively evaluate and be a predictive parameter for ARDS
      evolution. We will present the principle of the radio-isotopic method and some of
      its current clinical applications.

PMID- 16607735
TI  - [Complementary therapies in the treatment of bronchial asthma].
AB  - The clinical and paraclinical benefits of drugs that are not included in the
      standard therapy strategies, to patients suffering from bronchial asthma, are
      illustrated in a particularly rich specialty literature. Magnesium, furosemide,
      heparins, antioxidative drugs, nitric oxide donor substances have real qualities,
      that make them useful in the management of patients suffering from asthma. The
      tremendous amount of studies that inspired this work suggests that, for the
      asthmatic patients, there are other alternative therapies, which can be
      administrated as adjuvant medication to the classical medication. At the same
      time, unconventional treatments are a solution worth considering for treatment
      resisting cases, for cases in which side reactions develop to the standard
      therapy, and a source of inspiration for future research.

PMID- 16607736
TI  - [A possible prognosis score in corticosteroid-resistant nephrotic syndrome].
AB  - Chronic glomerular nephropathies in children are marked by an often unfavourable
      evolution, so that the establishing of a prognosis at the time of the diagnosis
      is both a professional and a moral duty for the pediatric nephrologists. The
      estimation of the current practice renal survival prognosis in children with
      chronic glomerular nephropathies, by using clinical and laboratory elements in
      different histological forms of primitive chronic glomerulonephritis (CGN), with
      a minimum period of observation of one year. We analyzed parameters that may
      intervene in the duration of renal survival: type of CGN, age at the debut of the
      illness, histological scores of activity and chronicity, the presence of tubular
      atrophy lesions and that of interstitial fibrosis, renal failure (RF) installment
      time, in cases with normal renal function at the beginning, the time until the
      initiation of dialysis in cases with ESRF, respectively. The statistic analysis
      of data has been carried out with Epi soft (Fischer test). The results have been
      as follows: unfavourable evolution has been taken into consideration in the cases
      which have presented fixed nitric retention or which required the initiation of
      dialysis. The initiation of dialysis was necessary in 19 cases (76%), out of
      which 11 (44%) having associated between 4 and 6 of the considered risk factors.
      If the histological type (SFGS, DGS, MPGN) is added to the obtained score, the
      accuracy of the estimation increases to 89%. In conclusion, the usage of
      prognosis scores composed of current elements of diagnosis that have proven to
      have statistical significance, as far as the renal survival prognosis is
      concerned, may allow the invoking of a medium-term prognosis in the evolution of
      children with CGN.

PMID- 16607737
TI  - [Clinical study of acute diarrhea caused by rotavirus].
AB  - To establish the implication of Rotavirus in acute diarrhea of babies and
      children. Prospective study on 164 patients aged between 1 month and 3 years with
      acute diarrhea, admitted in the Clinical Hospital of Infectious Diseases Iasi
      between 01.01.2005 - 31.03.2005. Rotavirus cause the illness in 30 patients
      (18.29%). The disease was more prevalent among children with dystrophy or with
      other comorbidities like: iron-deficiency anemia, intestinal parasitosis,
      rhinopharyngitis, pneumococcal meningitidis. In seven cases the infectious was
      considered to be nosocomial. During the illness patients also accused other
      symptoms, while in order of frequency were: common respiratory infection (13.3%),
      nausea and vomiting (40%), maculopapular eruption and intestinal pneumonia
      (16.6%), acute pharyngitis (10%). In this study latex agglutination confirmed the
      diagnosis. Vomiting and diarrhea led in all cases to moderate or severe
      dehydration. Appropriate rehydration was necessary but only in 12 cases was made
      through intravenous access with: Ringer lactate, isotonic sodium chloride
      solutions. Most children recovered with in 5 days.

PMID- 16607738
TI  - [Treatment outcome using prednisone in corticosteroid-responsive primary
      nephrotic syndrome in children].
AB  - In children, the nephrotic syndrome is usually corticoid-responsive;
      approximately 70% of patients experience relapses, frequently triggered by
      infections. Our paper presents the results obtained using a 4 month prednisone
      regimen. This retrospective study included 83 children afflicted with nephrotic
      syndrome over a 10 year span. We analyzed: age at diagnosis, boys/girls ratio,
      response to corticoid treatment - after one month of prednisone and at the
      completion of the treatment course, number of relapses and their frequency,
      complications of prednisone treatment. The median age at diagnosis was 4.8 years,
      males predominating M:F = 1.5:1. Complete response after 4 weeks of prednisone
      therapy was noted in 98.79% of cases. We had 116 episodes of relapses during the
      first year of follow-up, occurring in 67.4% of children (27.9% were frequent
      relapsers, 11.62% subsequently became corticoid-dependent). Late relapses, after
      the first year, occurred in 32.55% of cases. We noted mostly mild adverse effects
      of the prednisone treatment: occurrence of infections during therapy (16.27%),
      cushingoid facies (37.2%), hirsutism (4.6%), high blood pressure (4.65%), stretch
      marks (2.32%). In conclusion, the 4 month prednisone treatment regimen is
      efficient in inducing and maintaining a remission. The incidence of relapses is
      32.55%, comparable to the figure cited in larger studies. Serious adverse effects
      are significantly lower with this regimen compared to other corticoid treatment
      schemes. Key wo

PMID- 16607739
TI  - [Prospective epidemiologic considerations on asthma morbidity in patients
      admitted to the St. Maria Emergency Hospital Clinic for Children, Iasi].
AB  - Authors present the results of a clinical epidemiological assessment of a
      retroprospective study carried out on a sample of 6717 records of children
      assisted for asthma in the "Sf. Maria" Emergency Clinic Hospital for Children
      Iasi, between 1990-2004. The epidemiological and statistical mathematics methods,
      both classical and computerized, highlighted an increase in the incidence and
      prevalence values in 2000, as a consequence of National Program for Asthma. For
      the entire period of study, the morbidity values increased in the cold and
      transit season, due to the acute respiratory infections, and in the warm season,
      by the atmospheric pollen. The anatomic-physiological peculiarities of the
      respiratory tubes explained the higher prevalence of asthma in males aged until
      10 years old. Asthma had an increased incidence in the age groups of 4-6 years
      old (28.21%) and 7-9 (30.42%), as a result of the entrance in collectivities
      where there is a high risk for acute respiratory infections. A lower prevalence
      of asthma in young-age groups was explained by a difficult diagnosis. The results
      above-mentioned can offer orientations for the clinical epidemiological
      surveillance programs of asthma.

PMID- 16607740
TI  - Flaxseed supplementation in hyperlipidemic patients.
AB  - The aim of this study was to investigate the effect of daily consumption of
      dietary flaxseed (as a source of linolenic acid, LNA) on plasma lipid
      concentrations in mildly hyperlipidemic patients. METHODS: 40 hyperlipidemic
      patients with plasma total cholesterol greater than 240 mg/dL were distributed in
      3 groups: 10 patients who received hypo-lipidic diet (diet group), 10 patients
      who received hypo-lipidic diet plus statins (diet+HL group), 20 patients who
      received hypo-lipidic diet plus 20 g ground flax-seeds/day (diet+flax group).
      Body mass index (BMI), serum total cholesterol (TC), HDL-cholesterol (HDL-C), LDL
      cholesterol (LDL-C), triglycerides (TG) and cholesterol/HDL-cholesterol ratio
      were measured at the beginning and after 60 days of treatment. RESULTS: Flaxseed
      supplementation was associated with significant reductions in TC (-17.2%), LDL-C
      (-3.9%), TG (-36.3%) and TC/HDL-C ratio (-33.5%). There were no significant
      differences in absolute change in BMI nor in percentage change in TC, HDL-C, LDL
      C, TC/HDL-C ratio between flaxseed and statin groups. CONCLUSIONS: Dietary
      flaxseed significantly improves lipid profile in hyperlipidemic patients and may
      favorably modify cardiovascular risk factors.

PMID- 16607741
TI  - [Systemic amyloidosis. Case report].
AB  - The amyloid deposition in skeletal muscle is well known but a rare occurrence.
      The study reflects the morphoclinical picture in cardiac amyloidosis in a 51
      years old woman, having progressive cardiac failure and sinus node disease. A
      complete clinical evaluation of the patient showed a concomitant malignancy,
      plasma-cell myeloma. Muscle-cutaneous biopsy and a sulfated blue alcian staining
      was routinely performed to screen for amyloid. Histologically, amyloid was
      confirmed by the presence of deposits in the interstitium around perivascular
      region, or rarely, in the endomysial region. Focally, the muscles showed a small
      group atrophy and scattered regenerating muscle fibers and some degenerating
      myofibers. Generally, is known that prevalence rate of amyloid myopathy in muscle
      biopsy specimens is low (0.004%), and, as in our case, only a minority of
      patients have multiple myeloma, as well.

PMID- 16607742
TI  - [Rasmussen syndrome. Clinical study].
AB  - Rasmussen's syndrome is a specific progressive disease affecting primarily one
      hemisphere, accompanied by intractable seizures and leading to severe neurologic
      and mental deficit. The authors present one child with frequent partial motor
      seizures and myoclonic seizures refractory to antiepileptic drug therapy who was
      diagnosed with epilepsia partialis continua. After a period of 15 months the
      patient develops a spastic right hemiparesis and mental degradation. Association
      of this signs of the clinical picture lead to the diagnostic of Rasmussen's
      syndrome who was confirmed by the presence of localized EEG abnormalities and
      imaging studies.

PMID- 16607743
TI  - [Palliative therapy for malignant hepatic tumors with hyperthermia].
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide
      with an annual occurrence of one million new cases. The incidence of liver
      metastasis is much higher than the incidence of HCC. Overall nearly 50% of the
      patients with colorectal adenocarcinoma will develop liver metastasis. Surgical
      resection remains the "gold standard" for resectable hepatic neoplasms, but only
      a minority of patients present with lesions which are potentially curable. In
      these nonresectable hepatic tumors palliative treatment using focal necrosis by
      hyperthermia (radiofrequency, microwave coagulation therapy, interstitial laser
      photocoagulation, thermo-ablation with hot water steam) appear as a valuable
      alternative. Best results are reported in the case of associations of thermo
      necrosis with general or intraarterial chemotherapy. These methods of treatment
      can be performed by percutaneous, laparoscopic or open approach. Precise guidance
      of the focal necrosis can be realized using CT scan, IRM and intraoperative
      ultrasound exam and the results are evaluated by the same techniques. The key
      element in the management of the malignant tumors of the liver is the cooperation
      between surgeon, intensive care physician, oncologist and specialist in
      interventional radiology, to appreciate the indication of therapy. Further
      controlled trials are required to define the precise indications and long term
      results of these methods of treatment.

PMID- 16607744
TI  - Current trends in minimally invasive neurosurgery: neuro-endoscopy.
AB  - Minimal invasive neurosurgery refers to the technological advances accomplished
      in refining surgical access thus enabling neurosurgeons to reduce the morbidity
      and improve the accuracy and quality of neurosurgical procedures. Neuro-endoscopy
      comprises a promising minimal invasive technique being applied in an increasing
      amount of cases as diseases of cerebrospinal fluid dynamics, brain and spinal
      tumours, cysts, infections, evacuation of haematomas et al. Representing an
      important scientific modality neuro-endoscopy favours the rapid recovery of the
      patient and improves its postoperative quality of life. Personnel training is
      compulsory so that a safe operative performance is performed. Greater experience
      in the field would be necessary for broadened applications. Neuro-endoscopy
      presents exciting scientific possibilities in the future.

PMID- 16607745
TI  - [Cerebro-umbilical ratio--high fidelity indicator in ante-partum fetal disorder].
AB  - In this study, we have aimed to point out the reliability and importance of the
      cerebro-umbilical ratio obtained by Doppler exploration, in comparison with
      classical investigations, as well as to verify the diagnosis of ante-partum
      foetal disorder through the amount of the Apgar score at the fetuses having been
      monitored.

PMID- 16607746
TI  - [Significance of hysteroscopy in the diagnosis and treatment of infertility].
AB  - Hysteroscopy is an excellent additional instrument for evaluating the uterine
      characteristics in infertile women. Retrospective study analyses the importance
      of hysteroscopy in diagnostic and treatment of infertility. Patients were
      selected from 1st Clinic of Obstetrics and Gynecology Iasi during 1997 and 2004.
      Study group included 602 hysteroscopy performed in our clinic with 480 cases of
      infertility. 28.9% were primary infertility and 49.1% were secondary infertility,
      rest of percentage been intrauterine synechia, septum, polyps and foreign bodies.
      Polyp ablation located near the tubal ostia (50 cases), synechia repair (90
      cases), were the most common operative procedures. Good results in removal of
      foreign bodies (16 cases) were obtained pregnancy rate more than 75%. Operative
      hysteroscopy is similar to diagnostic hysteroscopy except that a ideal
      hysteroscope is used to allow operating instruments such as scissors, biopsy
      forceps, electrosurgical or laser instruments, and graspers to be placed into the
      uterine cavity through a channel in the operative hysteroscope. Fibroids,
      synechia, and polyps can be removed from inside the uterus. Congenital
      abnormalities, such as uterine septum, may also be corrected through the
      hysteroscope.

PMID- 16607747
TI  - [Specifics of therapy of tubal infertility in patients with endometriosis].
AB  - Our purpose was to define the best way of treating tubal infertility caused by
      endometriosis. We have studied 24 patients with tubal infertility caused by
      endometriosis; the etiology has been laparoscopically established in the 2nd
      Clinic of Obstetrics and Gynecology Iasi. The endometriosis score (r-AFS) was
      used to establish the therapy. We performed laparoscopic treatment when
      endometriosis was visible. Postoperative medical therapy (Diphereline, 3 months)
      was indicated; patients with ,,unpigmented endometriosis" received the same
      medical therapy. The rate of pregnancies in patients that had benefit of combined
      therapy: surgical and medical (n=9) was superior (44.4%) to that obtained in
      patients that were only surgical treated (n=15): 26.6% (Spearman correlation-
      0.6595, p < 0.0012). Endometriosis is an important etiological factor in female
      infertility. The pathway is mechanic as well as chemical and it justifies the
      combined therapy. There are better results, as fertility prognosis in patients
      with endometriosis that receive both, surgical and medical therapy.

PMID- 16607748
TI  - [Laparoscopic splenectomy for epithelial cyst of the spleen].
AB  - Splenic cysts of all types are a relatively rare entity. The origin of epithelial
      cysts of the spleen is controversial, most probably congenital in origin.
      Generally, epithelial cysts of the spleen are asymptomatic and discovered
      incidentally. We present the case of a 40-year-old woman with a 3.5 cm splenic
      cyst diagnosed four years before. The cyst raised progressively in dimension, the
      actual size being of 6.5 cm. Computed tomography scan and magnetic resonance
      showed a central splenic cyst in close relations with main splenic vessels. An
      initial indication of partial splenectomy was established, eventually a total
      splenectomy being performed by laparoscopy due to close relations of the cyst
      with the main hilar splenic vessels. The hemostasis was assured with the aid of
      Ligasure Atlas 10 mm instrument. The pathology examination revealed a
      multilocular splenic cyst with a cuboidal epithelial lining. Central localization
      of splenic cysts represents an indication for total splenectomy. Laparoscopy
      provides a minimal access method of obtaining pathological confirmation of
      diagnosis, reduction of cyst complications, and a short hospital stay. This
      article discusses different aspects of epithelial cysts related to pathology,
      diagnostic and indications for operative treatment, a review of the literature
      being also presented.

PMID- 16607749
TI  - [Therapeutic solutions in post-excision defects for plantar verrucous carcinoma].
AB  - Carcinoma verrucous--anatomoclinical entity histological high rate of
      differentiation of the spinocellular epithelioma, clinically associated with 3
      types of lesion. We present the therapeutical solution of a plantar carcinoma
      verrucous case, a large post-excisional defect-free flap transfer of latissimus
      dorsi muscle using microsurgical techniques.

PMID- 16607750
TI  - [Bleeding control in stab wounds to the great vessels at the neck base].
AB  - Stab wounds of the neck are a great challenge for every surgeon. Approximately
      25% of penetrating neck injuries results in a vascular lesion. Wounds being
      situated below the cricoid cartilage are associated with the great mortality and
      morbidity, having a global mortality between 12-20%. 2/3 of the vascular wounds
      at this level have a tragic end. We are going to present 3 cases of cervical stab
      wounds in zone 1 of the neck, with vascular lesions, in which we succeeded to
      control the hemorrhages throw a midline sternotomy combined with different
      extensions. After this small experience we think that in patients with wounds
      situated in zone 1 of the neck, who reach the hospital hemodynamically unstable
      or with active bleeding, urgent midline sternotomy combined with cervicotomy, or
      section of the clavicle, is the best way to control the hemorrhages. Using blunt
      digital dissection we can avoid unpleasant situations that can appear using
      instrumental dissection into the mediastinal hematoma.

PMID- 16607751
TI  - [Profound necrosis--complication of the orthopedic treatment in congenital club
      foot. A case report].
AB  - The treatment of congenital club foot implies orthopaedic and operative methods.
      The complications of the treatment may result, in particular cases, from lack of
      follow-up and cooperation between the child parents and the doctor. These cases
      are a challenge for the orthopaedic surgeon, requiring multiple interventions and
      with a high morbidity. We present the case of a congenital club foot with
      profound necrosis secondary to a cast compression, which was not recognized by
      the parents.

PMID- 16607752
TI  - [Castleman disease of the neck].
AB  - Castleman Disease is a rare disorder characterized by benign lymph node
      hyperplasia involving lymphatic tissue in the neck, mediastinum, abdomen, axilla.
      There are three types of Castleman Disease: hyalin-vascular type localized nodal
      involvement, asymptomatic form; plasma cell type and generalized and multicentric
      type. MATERIAL AND METHOD: Between 2000-2004, 5 cases with Castleman Disease
      hyalin-vascular type with cervical lymph node involvement were diagnosed and
      treated in E.N.T. Department of "St. Spiridon" Hospital Iasi. 2 of these cases
      are presented: a 24 year old male and a 13 year old female were admitted with a
      asymptomatic neck mass with slow progressive growth. Paraclinical exams
      (radiology, cervical and abdominal echography, CT scanner) confirmed the
      lymphadenopathy and excluded another localization. Differential diagnosis
      included tuberculosis, metastatic lymphadenopathy, lymphoma, branchial cyst etc.
      RESULTS: The treatment of choice was surgical excision by cervicotomy in all
      cases, followed by vascular proliferation and hyalinization in affected lymph
      nodes. Postoperative controls no revealed recurrences. CONCLUSIONS: The prognosis
      of localized form of Castleman Disease hyalin-vascular tape is better than
      multicentric form surgical excision is both diagnostic and therapeutic.

PMID- 16607753
TI  - [Thrombophlebitis of left cavernous sinus secondary to acute right sphenoid
      sinusitis].
AB  - Isolated sphenoid sinusitis is a rare, potentially destructive entity. Presenting
      symptoms are often vague and non-specific therefore the diagnosis is made late
      when complications have had already occurred. The most frequent complications of
      sinusitis are the neurological ones--being serious life--threatening conditions.
      We report a case of isolate right sphenoid sinusitis with concurrent
      thrombophlebitis of left cavernous sinus. Accordingly, we review the salient
      clinical features of this illness, with emphasis on the importance of a high
      index of suspicion, the potentially rapid and fatal course of the disease process
      and the aspects of the diagnosis and treatment. We also reviewed the predisposing
      factors of complications of sphenoid sinusitis.

PMID- 16607754
TI  - Molecular mechanisms in hormone-resistant prostate cancer.
AB  - Prostate cancer is the most common malignancy in males. Despite the efforts for
      an early diagnosis, approximately one third of the cases are diagnosed in
      advanced clinical stages. Prostatic cancer, as the function of normal prostate is
      dependent upon androgens. So, androgenic deprivation represents an effective
      treatment especially in advanced cases. Although, the majority of patients will
      initially respond to androgen blockade, consequently the hormone-resistance will
      develop and the tumor will progress. The mechanism that determines tumoral
      progression during the endocrine treatment is driven by genomic instability,
      characterized by activating mutations of androgen receptor gene (AR), progression
      of some cellular clones possible of neuroendocrine origin that become adapted to
      low concentrations of residual adrenal androgens, suppression of apoptosis, by
      bcl-2 oncogene overexpression and p53 mutations, and growth factors (IGF-1-
      Insulin-like growth factor, KGF--keratinocyte growth factor, EGF--Epidermal
      growth factor, TGF a, b- Transforming growth factor a and b, bFGF--Fibroblastic
      growth factor type b) regulatory effect through either a paracrine or an
      autocrine mechanism. The identification of molecular alterations that appear
      during prostate carcinogenesis, may lead to the identification of new molecular
      targets to prevent hormone-resistance and to improve the prognosis in prostate
      cancers.

PMID- 16607755
TI  - [New data about hepatic sinusoidal endothelial cell].
AB  - Liver sinusoids are irregularly dilated capillaries. The sinusoidal lining
      consists of a sample squamous epithelium. Endothelial cells constitute the major
      cellular element of the sinusoidal lining and form a discontinuous endothelium.
      These cells are separated by gaps 0.1-0.5 mm wide. The endothelial cells also
      show numerous intracellular pores or fenestrations. They perform important
      filtration function due to the presence of small fenestrations that allow free
      diffusion of many substances and show huge endocytic capacity. Liver sinusoidal
      endothelial cells may function as antigen-presenting cells (APC) and are also
      active in the secretion of cytokines, eicosanoids, endothelin-1, nitric oxide and
      some extracellular matrix components. They can store and metabolize substances as
      serum immunoglobulins, too.

PMID- 16607756
TI  - Computer-aided identification of renal corpuscle elements in RGB and HLS color
      images.
AB  - The qualitative and quantitative changes in the structure of the renal corpuscle
      allow the assessment of the glomerular involvement degree, defining each type of
      glomerulonephritis. Recently, several works dedicated to glomerulonephritis focus
      on the quantitative investigation, achieved by digital (numerical) image
      processing, where the identification of the interest elements is a key stage.
      OBJECTIVES: The aim of the study was the elaboration of a technique for
      constructing reliable color models in the RGB and HLS spaces for each element of
      the structure of the renal corpuscle. MATERIAL AND METHODS: We analyzed images
      captured from trichrome stained fragments of renal biopsy. Each image contained a
      single renal corpuscle. The identification procedure used the software tools
      specialized in color image analysis provided by the Zeiss KS400 environment.
      RESULTS: There were defined specific chromatic domains in the RGB and HLS space
      for the identification of the following elements: the Bowman space and the
      glomerular capillaries (white colored regions), the nuclei (brown colored
      regions), the mesangium (green colored regions). DISCUSSIONS: In order to get a
      relevant picture of the role played by the decisions made in the definition of
      the chromatic domains, we performed two tests for the modification of the
      chromatic domain allocated to the mesangium in the RGB and HLS space,
      respectively. CONCLUSION: The procedures proposed for the identification of the
      RGB and HLS color models can successfully replace the manual delineation of the
      renal corpuscle elements. Such models represent an important step in our research
      visualizing the future development of computer programs for automated
      measurements of renal corpuscle elements.

PMID- 16607757
TI  - [Anatomical considerations on the renal arterial segmentation].
AB  - We studied the arterial segmentation of the kidney observing the basic mode of
      finishing of the renal arteries and the distribution of the second order arteries
      in renal parenchyma. Our study was performed on 194 human kidneys resulted by
      evisceration and we have also analyzed the renal angiographies. As methods of
      study we used dissection, injection of plastic material followed by corrosion. In
      10.82% of cases we found 3 arterial segments: anterior; posterior; inferior polar
      (basal). In 39.69% of cases au we found 4 arterial segments: apical (superior
      polar); middle (meso-ventral); inferior (basal or inferior polar); posterior
      (retro-pyelic). We found 5 arterial segments in 83 kidneys (42.78%). The 5
      arterial segments are as follows: apical (superior polar); superior (meso-ventral
      superior); middle (meso-ventral inferior); inferior (basal or inferior polar);
      posterior (retro-pyelic). In 13 cases (6.7%) we found 6 renal arterial segments:
      superior polar (apical); superior pre-pyelic (meso-renal superior); middle pre
      pyelic (middle meso-renal); inferior pre-pyelic (meso-renal inferior); inferior
      polar (basal); retro-pyelic (posterior).

PMID- 16607758
TI  - [The significance of intestinal metaplasia related to gastric ulcer].
AB  - PURPOSE: Intestinal metaplasia is considered an intermediary stage of gastric
      carcinogenesis. Thus, we aim to investigate lesions of intestinal metaplasia
      diagnosed at patients with peptic ulcer. MATERIAL AND METHODS: Our study was
      achieved on a group of 212 patients, clinically diagnosed with gastric ulcer and
      having partial gastrectomy. The fragments obtained from the circumference, the
      basis and from around the ulcer were formalin-fixed (10%) and paraffin included.
      The specimens were stained routinely (HE) and with special methods (van Gieson,
      Masson, Gomori, PAS and Alcian Blue). RESULTS: Intestinal metaplasia was present
      in 36 cases (16.9%). It was noted as a unique lesion (in 10 cases), in
      association with chronic gastritis (23 cases) and with dysplasia (3 cases). Most
      of the cases (70%) displayed type I (complete) metaplasia characterized by the
      presence of enterocytes, goblet and Paneth cells. The glandular architecture was
      regular, with straight crypts, lined by mature, absorbtion cells and goblet cells
      producing sialomucins. 20% of the cases displayed type II (incomplete)
      metaplasia, with distort crypts, lined by a few absorptive and goblet cells and
      sparse Paneth cells. 10% of the cases presented type III (incomplete, colonic
      type) metaplasia with twisted crypts, increased cell density and stratification.
      The goblet cells in the adjacent mucosa of the malignant ulcers contained mainly
      sulphomucins, together with a few neutral mucins and sialomucins. The
      signification and the involvement of the intestinal metaplasia in the malignant
      transformation of the gastric ulcer are discussed. CONCLUSION: Since it
      represents a risk factor for carcinogenesis the identification of intestinal
      metaplasia in the context of the gastric ulcer is extremely important.

PMID- 16607759
TI  - [Present consequences of road traffic accidents worldwide].
AB  - The paper presents mortality, morbidity and socio-economical consequences of road
      traffic injuries in the world. WHO data show that during 2002 year there have
      been recorded 1.2 millions deaths and nearly 20 million injured or disabled
      people, as a result of road traffic crushes, most of them being reported by low
      and middle-income countries. According to WHO data for 2002, road traffic
      injuries accounted for 2.1% of all global deaths and ranked as the 11th leading
      cause of death. The economic impact of these injuries on individuals, families,
      communities and nations is enormous, costing countries between 1% and 2% of their
      gross national product.

PMID- 16607761
TI  - [Clinical and epidemiologic assessment of a group of patients suffering from
      mumps, hospitalized in a 23 years period].
AB  - Authors present the results of the evaluation of some epidemiological and
      clinical parameters, on a sample of 2101 inpatients suffering from mumps,
      hospitalized in the Clinic of Infectious Diseases Iasi, between 1981-2003. The
      annual hospitalization average was of 5.7%. Authors highlight a high incidence of
      mumps in males (68.1%), urban area (67.8%), and winter-spring season (62%). The
      most affected was the age group of 7-10 (21.5%), followed by 11-14 (17.3%), and 1
      6 (16.7%) and inpatients over 20 years old registered 25.1%. The clinical forms
      were varied: 30.6% cases without the affection of other glands and organs; 26.1%
      associated meningitis; 15.6% with orchitis; 2.5% with pancreatitis. Meningitis
      and orchitis were pointed out as primary infection in 3.8% and 3.4% cases,
      respectively. The clinical manifestation forms were: mild (14.8%); medium
      (84.5%), and severe (0.5%) and 146 cases (6.9%) were registered as nosocomial
      infection. The nature of the epidemic foci was established retrospectively:
      school (5.9%), preschool (1.4%), and familial (92.7%). All these aspects
      highlight the necessity of the epidemiological surveillance of risk groups and
      the inclusion of anti-mumps vaccine-prevention in the Extended Immunization
      Program.

PMID- 16607760
TI  - [Serologic assessment of measles herd immunity in the north-western region of
      Romania].
AB  - The most objective analysis of measles herd immunity could be made by sero
      epidemiological study. In the population of North-West area of Romania we have
      evaluated the measles immune protection through a seroprevalence study, using an
      age stratified sample of population in witch the subjects from Cluj and Bistrita
      Nasaud counties were voluntarily involved. The measles antibody concentration was
      determined by immunoassay method using Hycor test. The database was performed in
      Microsoft Access and the statistics in Epi Info 2000. Levels higher then 40
      arbitrary units (the cut-off of protection) of the measles antibody were met in
      80% (IC95% : 75.09-84.01) of all subjects, 82.4% of the females and 84.9% of the
      urban area peoples. 98.3% of all subjects had detectable antibody levels. The
      protection increased by age: the adults had protective levels in at least 90% of
      cases. Global vaccine efficacy was 64.7% (IC95 % : 56.5 - 72.9), moderately
      decreasing with increasing age (the correlation coefficient--58.1%). In the
      assessed sample, the measles protection was the highest in adults, women and
      subjects from urban areas. The vaccine efficacy was relatively small, but the
      majority of subjects had detectable titers of measles antibody.

PMID- 16607762
TI  - [Smoking habits in Timisoara's teenagers].
AB  - In the following study we've proposed to realize a comparison between the results
      obtained from two previous studies, regarding to smoking in 17 years of age
      adolescent population from Timisoara, along 10 years, in the period 1994-2004.
      We've revealed that the presence of this behavior is real in both studies and the
      trend is in an ascendant evolution. Compared with the boys, the girls have an
      increased tendency of daily smoking and smoke a greater number of cigarettes per
      day.

PMID- 16607763
TI  - [The dynamics of risk factors in traffic accidents in Iasi county].
AB  - Injuries caused by traffic accidents represent a major world public health
      problem, rather neglected up to now, but which can be efficiently dealt with on
      long term, thanks to joint efforts. The authors present the results of a
      descriptive study concerning the involvement of various factors in traffic
      accidents in the county of Iasi, in 2003. This paper highlights the fact that
      injuries caused by traffic accidents represent an important morbidity and
      mortality factor. The incidence was of 29.34 serious road traffic injuries for
      100,000 inhabitants, as compared to the 30.61 recorded at the national level,
      whereas the mortality rate--6.9 deaths for 100,000 inhabitants, illustrates a
      positive situation, as compared to the 10.28 recorded at the national level (p <
      0.01). The most frequent causes involved in traffic events were: pedestrians'
      carelessness, driving carelessness, inadequate speed, exceeding the legal speed
      limits, failing to give way, illegal passing. Due to the fact that traffic
      accidents are avoidable, descriptive epidemiology data may represent the starting
      point in taking preventive measures.

PMID- 16607764
TI  - [Disseminated infections due to Scedosporium apiospermum in a patient with
      anaplastic large cell lymphoma. A case study].
AB  - A 42-year-old man was diagnosed with hepatosplenic T-cell lymphoma in November
      2003. Remission was incompletely achieved despite 10 courses of chemotherapy. He
      developed fever (38.5-39 degrees C), chills, cough and morning expectoration
      after the 61 courses of chemotherapy. During this period, an ultrasound of the
      abdomen showed multiple hypodense lesions of the liver. Culture of the sputum
      yielded Scedosporium apiospermum. Fungal cultures from blood remained negative.
      The patient was treated with voriconazol. After one month from therapy, an
      ultrasound examination showed decreasing of hypodense lesions of the liver, and
      no further lesions appeared. Based on significant improvement of liver lesions
      with voriconazole therapy, we proposed the diagnostic "probable" disseminated
      infections due to S.apiospermum.

PMID- 16607765
TI  - [Oral modifications during menopause].
AB  - The menopause, a physiological process specific to elderly women (>50 years) is
      defined by various involutive phenomena occurred at general level and
      particularly in the stomatognatic system elements. The authors followed the
      influence of the oral contraceptives in changes of oral tissues during menopause.
      The study was carried on 148 elderly women during menopause split in two groups:
      group I (study group) who have used oral contraceptives in earlier years, group
      II (control group) without contraceptive therapy. The evaluation of the results
      was made using clinical exams and complementary investigations (X-ray,
      cytological, histopathological, mycological, salivary rate exams) and index
      quantification. The results showed the importance of the apparition of changes in
      to the oral tissues during menopause increased in comparison to the control
      group. Corresponding prevention strategies are the basis of oral health
      management in women at menopause.

PMID- 16607766
TI  - [Use of biopolymer membrane diplen-F in treatment of initial enamel carious
      lesion on smooth surfaces].
AB  - The aim of the study was to evaluate the possibility of using a fluoride product
      included in a biodegradable membrane in remineralization of initial enamel
      carious lesions. The membrane has anti-bacterial, anti-inflammatory and
      remineralization properties, with a long-term effect. The efficiency of this
      treatment was assessed by measuring the surface of the demineralization area and
      its depth. The results proved that the use of this membrane in association with
      remineralization therapy of the initial enamel carious lesions increase the
      chances of success and represents a simple solution easily accepted by the
      patients.

PMID- 16607767
TI  - Temporomandibular joint ankylosis. A possible complication in juvenile psoriatic
      rheumatism.
AB  - The authors present a rare case of bilateral temporomandibular joint ankylosis
      secondary to polyarticular juvenile psoriatic arthritis in a 24 year-old man. The
      patient first presented with arthritis of his right elbow joint at the age of 9,
      followed by involvement of the distal inter-phalangeal joints of his right foot
      and both sacroiliac joints. Serum rheumatoid factor was not detected. At the age
      of 16 he developed psoriatic lesions affecting his nails and skin. By the age of
      20, clinical and radiological evidence of arthritis was detected in his
      temporomandibular joint (TMJ). Subsequently, the patient developed bilateral TMJ
      ankylosis over a period of 4 years. The patient was managed by bilateral
      resection of the ankylosis bone blocks, mobilization of the mandible and
      interposition of Dacron material between the two neo-articular surfaces. 10
      months postoperatively the patient maintained an inter-incisal distance of 3 cm.
      Postoperative mechano-therapy was hindered by the limited use of the patients'
      hands.

PMID- 16607768
TI  - [The cariogram principle applied to the patients with high caries risk].
AB  - The "Cariogram" is a new concept, conceived initially as an educational model,
      aiming at illustrating the multifactorial background of dental caries in a simple
      way. This educational interactive program has been developed for better
      understanding of the multifactorial aspects of dental caries and to act as a
      guide in the attempts to estimate the caries risk. Caries risk is the probability
      that an individual will develop carious lesions, reaching a given stage of the
      disease in progression during a specified period of time, conditional that the
      exposure status for risk factors remains stable during the period in question.
      For patients with high caries risk, efforts should be made to increase the
      "chance" sector and reduce each sector responsible for caries risk and
      particularly the unfavorable one.

PMID- 16607769
TI  - [Quantification of caffeine from energy drinks with mass spectrometry method
      (LC/MS)].
AB  - A high performance liquid chromatography coupled with mass spectrometry method
      (LC/MS) for quantification of caffeine from energy drinks was elaborated. It was
      utilised a Zorbax SB-C18, 100 mm x 3.0 mm i.d., 3.5 microm column with a mobile
      phase containing methanol/ solution 0.2% formic acid in water. Detection and
      quantification of caffeine was based on monitoring the protonated molecular ion
      abundance (m/z 194.9). The quantification was made using the external standard
      method. The calibration curve were made on range 0.26-26 microg/ml for caffeine
      with a correlation coefficient greater than 0.995. There were analysed 12 energy
      drinks with a caffeine content between 13 and 34 mg/100 ml.

PMID- 16607770
TI  - [Chemical composition of one source of sodium chloride mineral water from Neamt
      county].
AB  - This paper describes the analytical study of a sodium chloride mineral water from
      Baltatesti Spa--Neamt county. From the obtained analytical data it was observed
      that the dominant ions are those of Cl- (48.11 mEq%) and Na+ (43.07 mEq%),
      respectively. Also, the water contains a significant proportion of Mg2+ ions
      (6.12 mEq%) compared with the one of Ca2+ ions (0.339 mEq%). It can be remarked
      that the analysed source consists of a very concentrated, hypertonic water with a
      high content in chlorine, sodium and magnesium. This kind of mineral water is
      recommended in external treatments.

PMID- 16607771
TI  - [Synthesis and toxicity of some new (sulfon-amidophenyl)-amide derivatives of N
      (m-nitrobenzoil)-D,L-asparagine].
AB  - In order to obtain new compounds with potential antibacterial activity some new
      (sulfonamidophenyl)-amide derivatives of N-(m-nitrobenzoil)-D,L-asparagine have
      been synthesized. The compounds have been obtained by decyclization reaction of 2
      (m-nitrophenyl)-4-(beta-amidomethyl)-delta2-oxazolinone with various
      sulfonamides. A toxicity study with determination of DL50 value has also been
      realized.

PMID- 16607772
TI  - [Phytochemical and microbiological characterization of two Allium cepa L.
      extracts in order to include in dermo-cosmetics].
AB  - We have obtained two Allium cepa extracts (C1 and C2) which were characterized
      from chemical and microbiological point of view. The C1 extract is the richest
      concerning the content in flavonoids, triterpenic acids, amino acids, compounds
      recognized for their beneficial effects in wound healing. All this data shows us
      the possibility of using the Allium cepa extracts in the treatment of wounds,
      scars. As well, the antimicrobial activity of the two extracts was evaluated. The
      C2 extract was efficient as antimicrobial agent, but there are necessary special
      preserving conditions.

PMID- 16607773
TI  - [Nanotechnologies and nanomedicine].

PMID- 16607774
TI  - [Gastroesophageal reflux involvement in ENT disorders].
AB  - It is admitted that gastroesophageal reflux patients may presents ear, nose, and
      throat (ENT) symptoms and signs, condition known as laryngo-pharyngeal reflux. It
      is estimated that as many as 10% of patients presenting to an ENT specialist have
      a clinical condition that might be attributed to gastroesophageal reflux. The
      diagnosis is challenging since no laryngeal signs are pathognomonic. A
      combination of ENT and esophageal symptoms and signs may suggest the necessity of
      further investigations. Adapted 24h pH study or better an esophageal impedance
      study may reveal the involvement of gastroesophageal reflux. Alternatively, a
      short trial with omeprazole or another proton pump inhibitor may be the simplest
      way for diagnosis. The standard treatment for gastroesophageal reflux is the
      valid treatment for these patients.

PMID- 16607775
TI  - [Gastrointestinal stromal tumors. Actual diagnosis and treatment].
AB  - Gastrointestinal stromal tumors (GISTs) are currently defined as c-Kit-positive
      mesenchymal tumors with specific histological characteristics. CD117 (c-Kit
      protein) is a growth factor receptor with tyrosine kinase activity and product of
      the protooncogene c-Kit. The most frequent sign is gastrointestinal haemorrhage,
      which occurs in approximately one third of patients. The evaluations which are
      necessary for diagnosis include clinical examination, immunohistochemistry
      analysis, endoscopic examination, X-ray, abdominal CT scan, ultrasound, MRI,
      exploratory surgery, biopsy or fine-needle aspiration of the tumor. Current data
      suggest a major role of a new tyrosine kinase inhibitor, imatinib mesylate
      (Glivec), for patients with metastatic or advanced disease. Surgical resection is
      the treatment of choice and offers the only chance for cure.

PMID- 16607776
TI  - [Medical treatment in diabetic retinopathy].
AB  - Diabetic retinopathy is a major cause of blindness worldwide with an expected
      increasing incidence. Tight blood sugar and blood pressure control have proven
      essential in preventing both appearance and evolution of retinopathy. Surgical
      treatments as laser therapy and vitrectomy have also been proved highly effective
      in preventing major visual loss in advanced stages of retinopathy. Continuous
      scientific research is leading to a better understanding of pathogenesis of the
      disease and thus an effective medical treatment is expected in both preventing
      and treating different stages of diabetic retinopathy. In this update we review
      ongoing clinical trials and also the knowledge from finalized clinical trials
      that were testing the clinical impact of experimental treatments or known
      therapies.

PMID- 16607778
TI  - [Metabolic abnormalities with hematologic manifestation].
AB  - These are unusual diseases in pediatric pathology. We present the morphologic
      aspects of peripheral blood smear and bone marrow smear of nine storage disease
      cases.

PMID- 16607777
TI  - [Carotid atherosclerotic alterations revealed at ultrasonographic examination in
      patients with coronary heart disease].
AB  - Carotid ultrasound examination is a noninvasive method with large indications in
      the evaluation of atherosclerotic lesions at cardiac patients. The aims of the
      study were: the ultrasound assessment of extra cranial carotid system at patients
      with coronary heart disease; relationship with the cardiovascular risk factors,
      lipid profile and echocardiographic data. METHODS: There were studied 47 patients
      with coronary heart disease (angina, myocardial infarction, ischemic
      cardiomyopathy, CABG). The evaluation included cardiovascular risk factors,
      clinical examination, serum lipids and glucose, echocardiographic data. The
      ultrasound examination of the carotid arteries included the measurement of the
      diameter and intima-media thickness (IMT) of the common carotid arteries, the
      presence and location of atherosclerotic plaques and the presence and severity of
      carotid stenosis. RESULTS: There was a significant increase of the diameter and
      IMT with age (p=0.009 respectively p=0.05). Males had a greater medium diameter
      than women (7.8 +/- 0.9 mm vs. 7.3 +/- 0.8 mm, p=0.04). There was no significant
      relationship between the cardiovascular risk factors (smoking, arterial
      hypertension, diabetes mellitus, dyslipidemia) and IMT. The thickness of the
      interventricular septum (at the echocardiographic examination) correlated with
      the IMT (p=0.03). All the patients with myocardial infarction revealed carotid
      atherosclerotic plaques and most of the smokers had carotid plaques (88.9% vs.
      44.8%, p=0.03). Patients with carotid plaques were older (60.9 +/- 10.1 vs. 54.8
      +/- 6.1, p=0.02). CONCLUSIONS: The incidence of carotid atherosclerosis increases
      with age; the carotid diameter is greater at males and older patients; IMT is
      influenced mainly by age; carotid plaques are present mainly at older patients,
      at smokers and those with myocardial infarction and can be considered an
      additional risk factor for vascular

PMID- 16607779
TI  - [Headache in children and adolescent in ambulatory practice].
AB  - Headache in children and adolescent represents one of the most frequent and
      potentially severe pathological conditions, requiring a paediatric consult. The
      purpose of the study was to establish the headache prevalence from the total
      paediatric consultations in ambulatory practice as well as to establish the main
      etiological causes of the headache. The study, including 400 children and
      adolescents (M/F ratio=150/250, U/R ratio=290/110) with headache selected from
      3100 cases between 2003 and 2004, in two practices (one general paediatric office
      and one paediatric neuropsychiatry office) from the Outpatient Clinic of the "Sf.
      Spiridon" Hospital of Iasi, has shown a prevalence of headache of 12.9%, the most
      affected age group being that of 5-12 years (52.5%). The etiologic study proved a
      high frequency of trauma 46.25%, ophthalmologic diseases 13.28%, psychogenic
      headache 10.75%, migraine 10%, general causes (infections, anaemia,
      hypoglycaemia) 9%, ENT causes 6.25%, intracranial causes 0.75%. The study
      confirms the necessity of a multidisciplinary approach, most causes being benign
      and the prognosis favourable in most cases.

PMID- 16607780
TI  - [Cardiac arrhythmia in amitriptyline poisoning in children].
AB  - Amitriptyline (Antideprin) determines severe intoxications, especially because of
      its cardiac side effects. METHOD: We studied 8 children (2-14 years old) admitted
      with signs of amitriptyline intoxication. RESULTS: The clinical picture revealed
      altered general status, generalized hypertonia, arterial hypotension up to
      collapse, mydriasis, coma and cardiac arrhythmia. ECG monitoring showed
      ventricular premature beats, isolated, couplets and triplets, ventricular
      tachycardia and torsade des points, severe ventricular repolarisation
      disturbances with diffuse subendocardial ischemia. The treatment consisted in:
      gastric lavage with activated charcoal, alkalinisation with sodium bicarbonate,
      antiarrhythmic drugs and sustained vital functions. All cases recovered in 4-6
      days. CONCLUSION: The severity of amitriptyline intoxication requires continue
      clinical and ECG monitoring, for early detection of some life threatening
      cardiovascular events. Thus, the treatment will be started early and will
      alleviate the severe prognosis of this intoxication.

PMID- 16607781
TI  - [Systemic lupus erythematosus with neurologic onset and secondary
      antiphospholipid syndrome. A Case Study].
AB  - A 39-years-old woman was admitted to our hospital with musculoskeletal complaints
      (myalgias and symmetric arthralgias in proximal interphalangeal,
      metacarpophalangeal joints of the hands and in knees), systemic symptoms like
      fever, fatigue, malaise and a six months previous history of a transient ischemic
      attack. The presence of antibodies to double-stranded deoxyribonucleic-acid (DNA)
      and antiphospholipid antibodies led to the diagnosis of systemic lupus
      erythematosus with secondary antiphospholipid syndrome. Cerebral infarction
      develops significantly more often in patients with lupus and antiphospholipid
      antibodies, but other clinical syndromes are associated with lupus anticoagulant:
      cognitive dysfunction, seizures, polyneuropathy, aseptic meningitis, myelopathy.

PMID- 16607782
TI  - [Difficult diagnosis in a case of pulmonary epidermoid carcinoma].
AB  - We present a case of a 66 years old male patient, from urban area, smoker for 54
      years, without special antecedents, hospitalized in our service with a pulmonary
      right lower lobe abscess, whose onset was 4 months ago, persistent under
      treatment in another pneumology service. Clinically and radiologically we
      suspected a pulmonary excavated right lower lobe neoplasia, but unsustained by
      fiber-bronchoscopy and thoracic computer tomography. By this reason the patient
      underwent exploratory thoracotomy and the diagnosis was confirmed by the biopsy
      of the resected specimen: pulmonary epidermoid carcinoma. The short term outcome
      was favourable.

PMID- 16607783
TI  - [Current trends in neovascular glaucoma treatment].
AB  - Neovascular glaucoma is divided in three clinical stages: rubeosis iridis,
      secondary open-angle glaucoma, and synechia of the angle-closure glaucoma. 36% of
      neovascular glaucomas occurs after central retinal vein occlusion, 32% after
      diabetic proliferative retinopathy, and 13% occurs after carotid artery
      obstructive. The key of success in the treatment of neovascular glaucoma is the
      early and rightly diagnosis, the treatment is aimed mainly at relieving pain, as
      the prognosis for maintaining visual function is extremely poor. The most
      important surgical procedures are trabeculectomy, artificial drainage shunts and
      cyclo-distraction by trans-scleral diode laser. This essay presents a synthesis
      of modern principle data concerning neovascular glaucoma.

PMID- 16607784
TI  - [The prevention of urinary tract injuries in obstetrics].
AB  - The aim of this study was to warn young obstetricians of the traumatic injuries
      to the urinary tract in their daily practice. After a short description of the
      changes that occur in pregnancy and puerperium at the urinary tract, we present
      "details" of some methods in order to avoid the urethral, bladder and ureteral
      injuries during vaginal delivery and some obstetric procedures (caesarean
      section, hysterectomy). This article represents a small and useful guide for
      young obstetricians in order to avoid unpleasant situations that can occur in
      their obstetric practice.

PMID- 16607785
TI  - [Assessment of prognostic factors in breast cancer].
AB  - Prognostic factors predict the long term outcome of treatment, recurrence rate
      and overall survival. Treatment decision is based on assessment of prognostic
      factors. They are classified as clinical (age, menopausal status, tumoral growth
      rate, inflammatory signs), histological (tumoral stage, pathological type,
      grading, tumoral necrosis, lymph nodes status, margins status) and biological
      factors (steroidal receptors pattern, ploidy etc). There are tumor markers
      currently evaluated, being considered conventional and new markers that are not
      usually evaluated. Patients with negative lymph node will show no recurrences
      after surgery and/or radiotherapy in 70% of the cases. Factors with specific
      prognostic value are used for deciding on the therapeutic strategy in negative
      axillary node cases.

PMID- 16607786
TI  - [Traumatic injuries to the spleen in adults].
AB  - The management of splenic injuries is still controversial, with an increasing
      trend toward non-operative treatment. The aim of this study was to assess for
      patients with splenic traumatic injuries, the treatment methods, the factors
      contributing in selecting appropriate management and the patients outcomes.
      Between 1994 and 2003, 77 patients were admitted and treated in our hospital for
      splenic traumatic injuries. There were 69 blunt (89.61%) and 8 penetrating
      injuries (10.38%). Nineteen patients were initially proposed for non-operative
      treatment, eventually only 5 patients (16.49%) were successfully treated (success
      rate 26.31%). Splenic conservation was used in 6 patients (7.79%; success rate
      100%) and splenectomy on 66 patients (85.71%). Indications for laparotomy were:
      hemodynamic instability (35 patients), peritonitis (9 patients) and the presence
      of hemoperitoneum and splenic injury (22 patients). Overall mortality was 7.79%,
      with 4 deaths in splenectomy group and 2 deaths in proposed non-operative group.
      In conclusion, conservative treatment of splenic injuries can be performed with
      good results and an increasing number of patients can be treated in this way. For
      this purpose are necessary a perfect selection of the patients, a surgeon skilled
      in conservative splenic techniques and good techniques facilities.

PMID- 16607787
TI  - [Acute surgical pathology in elderly patients].
AB  - The consequence of demographic aging is an increase of surgical pathology of the
      elderly, concerning both number and complexity of the cases. To asses the nature
      of geriatric surgical pathology and the effect of co-morbidities on surgical
      outcome, a retrospective study was carried out on a series of 401 patients aged
      over 75, treated in the IIIrd Surgical Unit in the period 2002-2003. 132 patients
      were admitted as acute cases and 94 of them were operated: 62 required immediate
      surgery and 32 required delayed operations. According to the nature of the
      diseases, benign surgical conditions were encountered in majority of the cases
      (78 cases). The diagnostics requiring immediate operations were: complicated
      hernias, perforated peptic ulcer, lower limb acute ischemia. Delayed emergency
      operations were performed for: acute cholecystitis, biliary lithiasis with
      angiocholitis and complicated gastric cancer. Cardiovascular pathology was
      recorded as the most frequent co-morbidity. Hospital mortality rate of 32.9%
      resulted mainly from cases with mesenteric infarction and generalized
      peritonitis, as well as from delayed emergencies such as complicated gastric and
      colon cancer. The most frequent causes of death following surgery were: cardiac
      failure, sepsis and multiple organ failure.

PMID- 16607788
TI  - [Clinical aspects of cardiac stab wounds: report of 20 cases].
AB  - Penetrating cardiac wounds are the most dramatic injuries which need a rapid
      diagnosis and surgical intervention. This clinical pathology has a high
      increasing incidence in the whole world. We aimed to present our personal
      experience in such cases. The study was carried out along a period of 31 years.
      From 1974 to 2004, 20 patients (mean age, 34 years; 17 male) with penetrating
      cardiac stab wounds were treated. The initial clinical presentation was cardiac
      tamponade ("blue injured"-8 patients, 40%), hemorrhagic shock ("white injured"-3
      patients, 15%), both being implied with 8 patients (40%), one of the aspects
      being predominant. One patient was stabile. All patients were immediately
      transferred to the operating room. The left ventricle was found to be the most
      frequent site of injury (7 patients, 35%), followed by right atrium (6 patients,
      30%), right ventricle (4 patients, 20%), left atrium (1 patient, 5%) and both
      ventricles (1 patient, 5%). There were 17 (85%) penetrating cardiac wounds,
      2(10%) penetrant stab injuries and one (5%) non-penetrant cardiac wound.
      Cardiorrhaphy was performed in all cases. The postoperative complication was
      pneumonia in 2 cases. In the present study, the survival rate was significantly
      high (80%). In conclusion, these promising results suggest that a wound with a
      severe prognosis may be turned into a relative trauma, harmless for the patients
      who will survive until surgical admission.

PMID- 16607789
TI  - [Hydatic cyst of the liver. Considerations on 337 cases].
AB  - Hydatid disease of the liver is still endemic in certain parts of the world. The
      modern treatment of hydatid cyst of the liver varies from surgical intervention
      to percutaneous drainage or medical therapy. Surgery is still the treatment of
      choice and can be performed by the conventional or laparoscopic approach. The aim
      of the study is to analyze the results of the surgical treatment in hydatid
      disease of the liver in First Surgical Clinic, Iasi. The study concerned a period
      of 12.5 years (1992 - 31.07.2004) and it included 337 cases. There were performed
      radical procedures (ideal cystectomy - 17 cases - 5.04%, hepatic segmentectomy -
      8 cases - 1.48%, atypical hepatectomy - 10 cases - 2.96%) or conservative
      procedures (de-roofing - 37 cases - 10.97%, subtotal pericystectomy - 34 cases 
      10.80%, total pericystectomy - 19 cases - 5.63%, partial pericystectomy - 212
      cases -62.90%). In 35 cases (10.38%) the operation was started laparoscopically
      and 12 cases needed conversion. Postoperative course was complicated in 112 cases
      (33.32%) (external biliary fistula, cavity suppuration, residual cavity hydatid
      relapse). Radical methods constituted operations that had excellent results, but
      they are feasible in few cases. Conservative procedures, relatively simple and
      still accepted, have a higher rate of morbidity. The laparoscopic approach is
      more and more used, with good results.

PMID- 16607790
TI  - [Anatomical and clinical evaluation regarding the removal of the peritoneal
      dialysis catheter].
AB  - AIMS: To describe CAPD technique survival and causes for catheter removal. The
      study included 320 end stage renal disease (ESRD) patients, initiated on CAPD
      between 1995-2003. Definitive catheter removal was required in 44 cases (15.1%),
      11 of these (3.79%) receiving renal transplant. Causes for catheter removal were:
      mechanical obstruction by fibrin (8 cases/2.75%), obstruction by tub bower (1
      case/0.34%), by omental muff (6 cases/2%); abdominal wall sepsis (30 cases/
      10.3%); non-responsive bacterial peritonitis (13 cases/4.05%), fungal peritonitis
      (7 cases/ 2.4%), fecal peritonitis (2 cases/0.68%); transfer to hemodialysis
      program (31 cases/10.6%); renal transplant (11 cases/3.79%); emergency surgical
      pathology for: necrotic-hemorrhagic pancreatitis (two cases), intestinal
      occlusions (six cases), locked hernias (three cases) and locked
      eventrations(three cases), appendicular peritonitis (two cases). Mortality
      associated with these procedures and underlying pathology was 1.73%.

PMID- 16607791
TI  - [Clinical study on the tolerance and efficacy of piroxicam used in cataract
      surgery, compared with diclofenac and indomethacin].
AB  - The study was done on 75 patients diagnosed with cataract, treated with non
      steroidal anti-inflammatory eye drops. This clinical trial recommends piroxicam
      0.5% as a reliable alternative of diclofenac 0.1% and indomethacin 0.1%.

PMID- 16607792
TI  - [Connective tissue modifications in the pelvi-perineal prolapse at menopause].
AB  - AIM: The qualitative and quantitative analysis of the histological structure of
      the Levator Ani (LA) muscle at female patients with pelvi-perineal prolapse
      (PPP). MATERIAL AND METHODS: After having taken biopsies of LA from 50 patients
      with PPP, a microscopic qualitative and quantitative study has been performed.
      This study was done by comparison with a control lot. RESULTS: The connective,
      muscular and vascular modifications in the structure of the LA are presented, in
      connection with the hormonal status of patients with PPP and also the influence
      of these modifications on the anatomic and functional integrity of the pelvic
      floor. CONCLUSIONS: Applying the hormonal maintenance treatment for menopause
      patients has become strictly necessary, both in the PPP prophylaxis and after
      restoring surgeries.

PMID- 16607793
TI  - [Prune-belly syndrome prenatal diagnosis].
AB  - We present the ultrasonographic diagnosis at the 19th gestational week in a case
      of Prune-belly syndrome which consists in abdominal wall distension with
      deficiency of the abdominal wall musculature, urinary tract abnormalities
      (specially mega bladder), and in males, cryptorchidism. The pathologic
      examination found the patient devoid of striated muscles anterior abdominal wall,
      hypertrophy of the urinary bladder, and urethral atresia. The Prune-belly is
      accessible to antenatal diagnosis and the variable prognosis does not always
      justify abortion.

PMID- 16607794
TI  - [Evidence-based colorectal cancer screening].
AB  - Colorectal cancer has been identified as an appropriate candidate for early
      detection and treatment of both asymptomatic individuals and those at risk of the
      disease. The lifetime incidence of colorectal cancer among persons at average
      risk is sufficiently high to justify screening the general population. This
      review presents the latest strategies employed in early detection of the
      colorectal cancer. An ideal screening test should satisfy some basic criteria:
      must be simple, secure, accepted by the population with valid and reproductive
      results. Despite the demonstrated benefits of colorectal cancer screening,
      incidence and mortality rates of this common cancer remain high. More optimally
      tailored screening tools are needed that combine the features of a potentially
      ideal screening test.

PMID- 16607795
TI  - [Modern morpho-functional concepts in cephalic arterial distribution].
AB  - The present paper provides a general morphofunctional study of the oro-maxillary
      facial cephalic arterial area that shows some particular hemodynamic
      characteristics. The internal maxillary artery supplies a very large territory,
      with numerous and wide anastomoses. In order to understand the hemodynamic
      characteristics of this artery, we analyzed some older theories, such as: Ludwig
      von Bertalanffy's General Systems Theory, Walter Zimmermann's Telome Theory, and
      some general rheological principles also.

PMID- 16607796
TI  - The morphologic changes induced by hormone and radiation therapy on prostate
      carcinoma.
AB  - The morphologic changes induced by hormone and radiation therapy were evaluated
      in prostate biopsy and prostatectomy specimens from patients with residual
      prostate carcinoma. The two therapeutic methods induce changes both in the
      nonmalignant and malignant residual prostatic tissue. Following hormone therapy,
      the nonmalignant prostatic tissue showed atrophy of prostatic acini associated
      with fibrosis, basal cell hyperplasia, degenerative changes of the secretory
      epithelial cells, and a marked decrease of high-grade intraepithelial neoplasia
      (HGPIN). In the fragments of residual carcinoma, squamous cell metaplasia,
      necrosis, and necrobiosis in the foci, vacuolization of the cell cytoplasm,
      smaller, rare nucleoli, intraluminal crystalloids, higher Gleason score
      associated with a lower capsular penetration, areas of necrosis and mitoses were
      found. Following radiation therapy, the nontumoral prostatic tissue showed an
      increased number of atrophic acini, squamous cell metaplasia, and presence of
      atypical glands. The morphologic changes induced by radiation therapy in the
      residual prostatic carcinoma were characterized by an abnormal architectural
      structure of the glands and presence of cell atypias correlated with the
      biochemical lowering of serum PSA.

PMID- 16607797
TI  - Adenosquamous cervical carcinoma morphological characteristics.
AB  - Adenosquamous carcinomas range between 5-25% of cervical cancers and are composed
      by an admixture of malignant squamous and glandular elements. The aim of our
      study was to identify some common characteristics and to evaluate the correlation
      between the degrees of differentiation of the two components. We analyzed 15
      cases diagnosed in a 6 years period. The age ranged between 26 years and 67 years
      (mean age 46.5 years). Paraffin embedding, followed by HE staining were
      performed. Differential diagnosis with endometrioid adenocarcinoma of the cervix
      with squamous metaplasia was made. Four cases (26.66%) were subtyped as clear
      cell adenosquamous carcinomas and 2 cases (13.33%) were subtyped as glassy cell
      carcinomas, exhibiting finely granular ground glass type cytoplasm. 93.33% of
      cases exhibited a poorly differentiated squamous component and 66.66% of cases
      exhibited a well differentiated glandular component. 20% (3 cases) presented
      prominent lymphoplasmacytic and eosinophilic inflammatory tumoral infiltrate.
      Squamous intraepithelial lesions in overlying epithelium was observed in 4 cases
      (26.66%). One case presented extension to the uterine body. One case, diagnosed
      as glassy cell subtype, presented regional lymph node metastases. Our study
      concluded the occurrence of adenosquamous cervical carcinomas at a similar age
      with squamous cervical carcinomas in the investigated group of patients. As
      adenosquamous cervical carcinomas are considered expressions of a biphasic
      differentiation of a single pluripotential sub-columnar reserve cell, a similar
      degree of differentiation of the two components would be expected. Although, we
      registered a degree of variability in grading of the two components, with a
      tendency of squamous component toward poorly differentiated aspect and a slightly
      dominant aspect of well differentiated glandular pattern.

PMID- 16607798
TI  - [Some particular aspects in cases of pleomorphic adenoma of the parotid gland].
AB  - Twenty three cases of parotid gland pleomorphic adenoma from Surgical Oro-Maxillo
      Facial Clinic of "Sf. Spiridon" Hospital, Iasi, have been evaluated. In order to
      reveal the particular microscopic aspects, several histological techniques have
      been used: HE, Van Gieson, PAS, Alcian Blue and Gordon Sweet. The microscopic
      evidences points out the variety of microscopic forms even within the same case,
      and also the prevalence of some particular forms such as myo-epithelial cell
      predominance, squamous metaplasia and cystic degeneration. Our observations,
      corroborated with the one from other research, support the hypothesis of an
      unique ectodermal cell origin for the lesion histogenesis.

PMID- 16607799
TI  - [Diagnostic difficulties in mammary gland adenosis. Case report].
AB  - Tumor adenosis represents a rare lesion, which most frequent appears as a
      palpable mass, with more than the usual dimensions. The paper presents a case of
      tumor adenosis of the mammary gland of a 16 years girl. Macroscopically, the
      tumor was well delimited, with gray-white surface and a nodular aspect on
      section. The tissue was processed by routine technique and stained with
      hematoxylin-eosine (H&E). There were also performed immunohistochemical (Actin
      SM, CK, S100) and special stainings (silver impregnation). Microscopically, there
      were observed several histologic types of adenosis, the most frequent being
      sclerosing adenosis. Through silver impregnation it was observed that the
      basement membrane, which surrounded the tubes, was intact. Immunohistochemically,
      there were evidentiated the epithelial and myoepithelial components of the tubes.
      The presence of these elements led through the diagnosis of tumor adenosis. The
      importance of recognition of the tumor adenosis is found in the possibility of
      wrong interpretation of this with tubular invasive carcinoma, these two entities
      being often mistaken, mainly at the frozen-section examination.

PMID- 16607800
TI  - [The method of conditioned place preference in pharmaco-dependence research].
AB  - Conditioned place preference (CPP) is a paradigm for evaluating pharmaco
      dependence related issues besides other animal models (withdrawal syndrome
      evaluation, self administration, behavioural sensitisation, drug discrimination).
      CPP is used for evaluation of motivational properties of substances (but also for
      non pharmacological stimulus). It consists in repeated association between a
      primary unconditioned properties of a stimulus (usually a substance) with a
      distinct environment. After a number of such associations, the unconditioned
      stimulus become conditioned stimulus and may emerge a response when the animal is
      exposed to these (the conditioned compartment). The response may be quantified as
      the time spent in the conditioned compartment. Our studies show an agreement
      between misoprostol (stable PGE1 analogue) effect on alleviating morphine-induced
      experimental pharmaco-dependence and morphine-induced CPP.

PMID- 16607801
TI  - [Mortality in a district hospital--an indicator for efficiency].
AB  - The paper presents mortality in surgical units of a second referral hospital from
      Galati. During 2003 year there have been recorded 190 deaths, most of them being
      reported by neurosurgery department (132). Hospital mortality varied from 2.8
      deaths per 100 inpatients in neurosurgery to 0 deaths in urology and obstetrics
      gynecology department. The surgical procedure with the highest number of deaths
      has been craniotomy (133). The death risk during operation was very low for most
      of surgical procedures, medium in the first 24 hours and high after 48 hours.

PMID- 16607802
TI  - [Nutrition in preschool children from Baile-Herculane].
AB  - In the effected study we investigated the feeding quality in Baile-Herculane,
      during the period 2003-2004. The study was realised in two samples consisted in
      659 preschool children (55% girls and 45% boys) and 359 children (65% girls and
      35% boys) respectively, homogenous and statistical representative. The method
      consisted in feeding investigation using based on food lists consulting, effected
      2 times in a year, in the winter season (November) and in the spring season
      (April). The inquiry period was 10 days consequently, in each season. We had
      established the nutritive value of feeding portions in two months (November and
      April), counted the average of the nutritive ration for the both investigated
      periods and compared them with nutritional necessity established for the same age
      group. We investigated the menu structure and diversity. In the first period of
      feeding investigation (November 2000) we established a decreased intake of foods
      which determine a small intake of calories, proteins, minerals and vitamins under
      the nutritional necessities. In April the nutritive value of the consumed food
      was less than in November. The decreased consumption of milk, cheese, eggs,
      vegetables and fruits determined a less intake of calories, fats, minerals and
      vitamins than nutritional necessities. The increased intake of bread, cereals and
      meat caused increased values of carbohydrates, vitamin B1 and iron. The menu was
      divided in two meals and a snack (breakfast - 15%, snack - 15%, lunch 50%). The
      menu variation and courses' succession were in line with the hygienic-sanitation
      rules.

PMID- 16607803
TI  - [Epidemiologic aspects of sudden death in the Constanta District].
AB  - This study is aimed to clarify some aspects of the cardiac sudden death (CSD) in
      the context of the general pathology. 5842 cases were taken into study,
      representing the total number of autopsies performed in the Forensic Department
      of Constanta District between 1997-2002 (subjects of both sexes aged 6 months to
      82 years). Sudden death represents 80% of the non-violent death cases. We found
      1563 cases of sudden death, out of which 891 were CSD (57%). The yearly
      distribution of the CSD cases was: 1997 - 205 cases (58.23%), 1998 - 164 (56%),
      1999 - 161 (60%), 2000 - 121 (67.6%), 2001 - 98 (52.4%), 2002 - 142 (50.17%).
      Coronary atherosclerosis was the cause of 78% of the CSD. They are followed by
      far by other causes: respiratory (24.3%), meningo-cerebral (5.05%), digestive
      (2.3%), endocrine (1.85%), infectious (1.6%), the syndrome of the child sudden
      death (1.28%), renal (0.64%), neurological (0.57%), allergic (0.9%),
      hematological (0.32%), the syndrome of the sportsmen sudden death (0.32%). These
      figures are age-dependent: between 45-65 years of age the
      cardiovascular/respiratory causes ratio is of 5/1 ; it decreases to lesser ages
      to become inversed (1/2). The ratio to the meningo-cerebral causes is of 25/1 and
      largely decreases so that over 70 years of age it becomes usually 2/1 and
      sometimes 1/1.

PMID- 16607804
TI  - [Dental educational level of teachers in three primary schools in Iasi].
AB  - METHOD: We assessed the level of dental education of 120 teachers from 3 primary
      schools using a 13 question interview. RESULTS: The information on the etiology
      of dental decay is more accurate in female than in male teachers (53.15% vs
      47.56%). Knowledge of prevention is also better in female teachers. Nutrition
      information level is average, older teaching staff possesses a higher level of
      knowledge. The main sources that are used in order to access the information are
      represented by television, books and journals. The teaching staff's involvement
      in dental education varies widely, from non-involvement to almost 80%.
      CONCLUSION: The level of teaching's staff dental education is average and a
      greater involvement is needed in order to improve the dental health of school
      children.

PMID- 16607805
TI  - [Susceptibility to norfloxacin of some bacterial strains causing urinary
      infections].
AB  - The purpose of this study was to evaluate the in vitro activity of norfloxacin in
      comparison with ofloxacin, pefloxacin and ciprofloxacin against 662 strains. The
      studied strains were obtained from urine, during 2003 period, in Eastern region
      of Romania. The minimum inhibitory concentrations (MICs) were determined on
      Mueller-Hinton agar by the dilution technique, with an inoculum of 10(5)
      CFU/spot. Among tested quinolones, norfloxacin has the better activity against
      tested strains. The fluoroquinolone compounds were very potent against
      Escherichia coil strains. Our data shown the spread of quinolone resistance in
      our area and demonstrated the necessity of adequate antibiotic use in the
      hospital and community.

PMID- 16607806
TI  - [Screening methods for detection of metallo-beta-lactamase producing gram
      negative rods].
AB  - Modified Hodge test and a method using a disk with imipenem plus 1000 mg of EDTA
      were used to determine the presence of metallo-beta-lactamase producing gram
      negative rods among 166 clinical isolates from hospitals in Iasi and Galati. Of 9
      imipenem resistant strains found, only one Pseudomonas aeruginosa gave positive
      results with both tests and other two P. aeruginosa clinical isolates gave
      negative results with both tests. The rest of the strains (2 P. aeruginosa, 2
      Acinetobacter baumanii, 1 Sphingomonas paucimobilis) did not give conclusive
      results. These screening methods are useful, simple and accessible to clinical
      laboratories. PCR is needed to confirm the presence of metallo-beta-lactamase
      gene in bacteria and to determine the type of the enzymes.

PMID- 16607807
TI  - [Some aspects regarding the activity analysis of a military hospital].
AB  - Providing secondary health care for military staff and related personnel,
      Clinical Emergency Military Hospital "Dr. Iacob Cihac" it is the biggest hospital
      among those having the same profile. There are many factors with influence upon
      hospital's activities. Some factors can be measured (number of beds, the
      prevalence of a certain disease in population), but also some of them are
      subjective, creating pressures in hospitals utilization (costs, status of the
      professionals and hospital, desires of patients and their families). Good
      statistical information about hospitalized morbidity provides the basis for
      planning, control and efficient administration and can also serve as an input
      into the development of more effective preventive health strategies. There are
      some important differences between public own hospital and military hospital: for
      public hospitals, the main cause of morbidity is represented of respiratory
      disease, while for the military hospital on the top are nervous and psychiatric
      diseases; also, it is different the proportion of inpatients according to age
      groups - for public hospitals the main proportion of inpatients is aged more than
      45-60 years old, but for the military hospital there are also well represented
      those aged under 29 years old. The differences between the average length of stay
      in hospitals is due to hospitalization of psychiatric diseases in public
      hospitals.

PMID- 16607808
TI  - [Prioritization of the main health problems having impact upon the activity of
      the Emergency Military Hospital "Dr. Iacob Cihac" of Iasi in the years 1995
      2003].
AB  - The various health problems that are faced by a hospital institution at any given
      point in time, compete for the usually limited resources that are available,
      while the health needs are infinite.Therefore, the prioritization process is a
      key to a functional activity. The prioritization method involves the formal
      selection criteria and system used to prioritize the health conditions. The
      Hanlon method is a quality one, and considers the following criteria: the
      magnitude of the problem, the severity of the problem, the predicted
      effectiveness of the intervention, and the feasibility of intervening to address
      the problem. This method requires a technique to allocate a score for each
      criterion and each health condition. According to hospitalized morbidity rates
      registered between 1995-2003, using prioritization method, we detected the main
      causes to address for improving the activity of Emergency Military Hospital "Dr.
      Iacob Cihac" Iasi through a better selection of the inpatients and primary health
      care and community involvement. The presentation of the results situated on the
      top cardiovascular diseases, and on the last place the bone and articular
      diseases.

PMID- 16607809
TI  - [Study of dental chromatic space].
AB  - Dental chromatic space has been the topic for many studies and most of all
      indicated that dental structures are very versatile from the colour point of
      view, therefore a proper shade selection is difficult to made. Our study made a
      comparison between the shades of dental structures of men and women of different
      ages, the measurements being done in three regions: incisal, middle and cervical.
      We used a spectrophotometer Spectra-Flash 600 and the PC programme Data-Master
      version 2.3 for both chromatic determinations and the statistical evaluations.
      The study proved that there are no major differences between the dental shades of
      men and women; meanwhile chrome increases with age and from incisal to cervical
      regions. Also, value increases from incisal to cervical region.

PMID- 16607810
TI  - [Prevention of root fracture using posts reinforced with fiberglass].
AB  - (The aim of this study was to evaluate the fracture strength and mode of failure
      of endodontically treated teeth reconstructed with glass fiber reinforced posts.
      Twenty maxillary central incisors, extracted for periodontal reasons, were
      divided in 2 groups: gr. 1 - glass fiber posts, and gr.2 - control
      (endodontically treated but without posts). All samples were embedded in resin
      bloks and mounted in stainless steel cylinders for the compressive test. The
      force was applied on oral surface of the crown, until the failure occurred. The
      compressive loads at failure were recorded and compared with the statistical
      method Student t. The mode of failure of the specimens were also evaluated. The
      statistical analysis of the force values showed no significant difference between
      the groups. In conclusion, because of their low Young's modulus, the non-metallic
      posts made of resin composite reinforced with glass fibers have a protective
      effect on the dental tissues, the recorded mode of failure being very similar
      with the control group.

PMID- 16607811
TI  - [The effect of antihypertensive drugs on the anaesthetic effect of lidocaine in
      hypertensive patients who need dental treatment].
AB  - The study evaluated the influence of atenolol/nifedipine on the local anaesthesia
      with lidocaine in 64 patients with essential arterial hypertension following
      dietetic regimen and divided in: control group (21 patients), atenolol-treated
      group (21 patients with atenolol therapy) and nifedipine-treated group (22
      patients with nifedipine therapy). Atenolol/nifedipine was administrated three
      hours before anaesthesia (1.5 mg lidocaine/kg body weight) applied on Spix Spina.
      The atenolol/nifedipine influence on the anaesthetic intensity was evaluated both
      by the patient and dentist using scales for the appreciation of pain intensity
      (Visual Analogue Scale, Numerical Rating Scale) at 0 minutes (before
      anaesthesia), 5, 10, 20, 30, 60 minutes (moments for the determination of
      lidocaine plasmatic concentrations). There were no statistically significant
      differences between the values appreciated by the patient and dentist. Our data
      demonstrated a significant decrease of pain intensity in patients treated with
      atenolol/nifedipine. Very good inverse correlation was found between lidocaine
      concentrations and pain intensity.

PMID- 16607812
TI  - Root, stem and leaf anatomy of Geranium palustre Torner Cent. (Geraniaceae).
AB  - An anatomical study on the root, stem and leaf of Geranium palustre Torner Cent.
      has been performed in order to continue our previous researches on this species.
      Technique of inclusion into paraffin and optical microscope have been used. Root,
      stem and leaf transverse sections were studied. They contain calcium oxalate
      crystals as inclusions. The root presents elements of secondary structure (suber,
      secondary cortex, secondary xylem and phloem). The vascular bundles in the stem
      can be classified as internal or external and differ in the presence or absence
      of an own sclerenchyma sheet depending on their age. The vascular bundles of stem
      are collateral. Leaf structure is bi-facial. Stem and leaf surface have no
      glandular hairs.

PMID- 16607813
TI  - [UV spectrophotometric assay of famotidine in combination with picrolonic acid,
      picrolinate].
AB  - Famotidine, belonging to H2-antagonist group, is a compound containing a
      thiazolic moiety and it is used in peptic ulcer therapy. This paper debates the
      possibility of developing a new ultraviolet spectrophotometric assessment by
      using the reaction between famotidine and picrolonic acid. We carried out our
      determinations at 362 nm, where the absorbency of famotidine - picrolonic acid
      complex is maximal, and we have established the optimal reaction conditions. This
      method was successfully applied for famotidine assay from pharmaceutical dosage
      forms.

PMID- 16607814
TI  - [Membrane-selective electrodes for drug analysis. Note II].
AB  - Seven membrane-selective electrodes with PVC matrix and liquid-membrane for N
      butylscopolamine with different electroactive materials are presented. These
      electrodes have a linear response in the concentration range of 10(-6) - 10(-2) M
      N-butylscopolamine bromide, with a detection limit between 4.58 x 10(-7)M and
      1.09 x 10(-6)M. These electrodes were used with good results for quantitative
      assay by direct potentiometry and potentiometric titration of N-butylscopolamine
      bromide from pharmaceutical formulations. Recovery was between 95.50% and 99.20%
      for N-butylscopolamine bromide of injectable solutions.

PMID- 16607815
TI  - [Comparative study of several sulfurated mineral water sources from Iasi County].
AB  - The comparative study aimed the actualization of the analytical panel of some
      mineral water sources, sulfurated, iso- and hypertonic (existing in Nicolina
      area, Iasi county), that is the constant physico-chemical composition, in order
      to signal the alteration of water's quality. From the performed analysis, along
      the time and the presented ones, it can be observed than the sources maintain
      intact, along many decades, the chemical composition and their physical
      characteristics, and also their therapeutical action, due to the fact they are
      localised deep underground.

PMID- 16607816
TI  - [Descriptive motor sciences].
AB  - The paper presents a new approach to human movements and positions using
      Descriptive Geometry, a discipline used in 2D and 3D description of object
      positions in space. Some particular positions of the human body are depicted
      using a reference system formed by three orthogonal planes: horizontal, vertical
      and lateral. Positions of arms are described using precise terms used in
      Descriptive Geometry. The use of precise terms in human positions description can
      improve communication and understanding of more complex positions in space.

PMID- 16607817
TI  - [E-health application for home monitoring of neuro-muscular rehabilitation].
AB  - In many medical fields the recovery of muscular activity or its improvement up to
      the level of the optimal parameters is required. Apart from the classical
      solution for rehabilitation (physical exercises) the use of electrical
      stimulation has become quite frequent of late. The paper presents an interface
      that detects the electromyographic (EMG) activity, assesses it, and generates
      appropriate electrical stimuli, by means of a specific type of fuzzy control
      system, in order to control the dynamics of the EMG. The proposed interface will
      detect the motion and muscular activity, it will evaluate and generate the
      electrical stimulus using a fuzzy system tuned by dynamic of motion. The
      application will transmit e-Health information to the physician via Internet,
      synthetic, at request using TCP/IP stack and SMS services for wireless
      communication.

PMID- 16607818
TI  - [Preliminary pharmacological study on a "magnetic" drug complex].
AB  - Standard therapy requires high amounts of drugs, with subsequent risks of harmful
      effects on normal tissues. A treatment method that possible can avoid these risks
      is based on magnetic carriers (the method is designated also as magnetic carrier
      technique). The method consists in the selective attachment on a micro particle
      (permanent or reversible bonds), with strong magnetic moment, of an entity with
      no intrinsic magnetic properties (cells, microorganisms, antibody, antigens or
      chemicals), followed by external magnetic field targeting of the complexes
      ("active targeting"). The aims of this study were (1) to evaluate the acute
      toxicity of two original ferro-fluid (ammonium oleate and sodium oleate-based
      ferro-fluid) and (2) to assess the diclofenac (non-steroidal antiinflammatory
      drug, NSAIDS)--sodium oleate-based ferro-fluid efficiency in an acute
      inflammation model. We founded ammonium oleate-based ferro-fluid to have a strong
      dose-dependent toxicity, possible trough in vivo ammonium ions release; sodium
      oleate based-ferro-fluid seems to have a less toxicity. Diclofenac, diclofenac
      ferro-fluid complex and ferro-fluid alone, each blocks the 6 hours inflammatory
      peak and the first two block also the 72 hours inflammatory peak. We conclude
      that the diclofenac-ferro-fluid complex is probably concentrated in the area of
      external magnetic field application, leading to a stronger effect of the
      antiinflammatory drug. Taking in consider our results we cannot exclude a
      possible summation of the individual effects of diclofenac, ferro-fluid, and
      external magnetic field on the inflammatory phenomenon.

PMID- 16607819
TI  - [From reductionism to complexity].

PMID- 16607820
TI  - [Major impact of arteriosclerosis on cardiovascular morbidity and mortality].
AB  - Arterial stiffness (arteriosclerosis) is a diffuse process affecting the media of
      large arteries, strongly linked to the process of ageing, but influenced by
      several other major factors like hypertension and vascular calcifications.
      Arteriosclerosis has been recognized in recent years as a novel non-traditional
      cardiovascular risk factor both for renal and non-renal general population. Two
      of arterial stiffness parameters, pulse wave velocity and the augmentation index-
      determined by applanation tonometry, are strongly correlated with cardiovascular
      morbidity and mortality, as well as with the general mortality. Arterial
      stiffness, due to several factors related to the uremic milieu, is more
      pronounced in patients with end-stage renal disease compared with patients
      without renal dysfunction. The authors are briefly reviewing the most recent
      literature regarding the impact of arterial stiffness on cardiovascular outcome.
      Identifying the factors associated with reduced arterial compliance may
      positively influence cardiovascular outcome in the general population, and
      particularly in renal patients, plagued by a high burden of cardiovascular
      disease.

PMID- 16607821
TI  - [Can the child with congenital heart disease have a normal life-style?].
AB  - Is it possible for the child with Congenital Heart Disease to have an adequate
      life-style? The life-style of the child mainly depends on the life-style of
      his/her family. Consecutively, the parents themselves must adopt a healthy life
      style to be a good example for their children; on the other side, certain
      restrictions (hyponatremic regimen, the limitation of the physical activity) must
      be shared among entire family, the education of the parents being essential. To
      accomplish this, there must be an interdisciplinary team, including the GP, the
      cardiologist, the psychotherapist and the physiotherapist. This article discusses
      the factors influencing the life-style, their dependence on the family social
      status, on the diagnosis, on the child's age. The psychotherapeutic approach
      becomes very important at puberty. There is also essential the transition to the
      adult life, so these children will benefit of maximum of choices in life.

PMID- 16607822
TI  - [Metabolic syndrome. Some specifics of diagnosis for cardiovascular prevention].
AB  - AIM OF THE STUDY: To analyse obesity and metabolical complications
      (cardiovascular disease) in an obese population, Iasi county compared to the
      nonobese population of the same locality. MATERIAL AND METHOD: Cross-sectional
      study on two groups: group 1--the witness group--48 cases normal weight and group
      2--the study group--50 obese patients. RESULTS AND CONCLUSIONS: High values of
      abdominal perimeter (AP) associate with high glycemia, high triglycerides and low
      HDL-col in obese patients; higher evidence of X syndrome elements association in
      the obese population; higher global risk for the obesity in modern life
      conditions; teenagers obesity trigger are small birthweight and perinatal
      malnutrition in 30% of cases.

PMID- 16607823
TI  - [The effects of inhaled corticoids on bone density in asthmatic children].
AB  - OBJECTIVE: To evaluate bone status of asthmatic children on chronic inhaled
      corticoid therapy. METHODS: Bone densitometry was performed by Quantitative
      ultrasound (QUS) of the distal radius in 74 asthmatic children, evaluating Z
      score; serum levels of 25 hydroxyvitamin D were measured in 10 cases. RESULTS: 28
      of 74 children had osteopenia, defined as Z scores lower than -1. Statistic
      analyzes showed a significant correlation (p <0.05) of osteopenia with the
      duration of inhaled corticoid therapy (CSI), the absence of correlation with the
      dose of CSI, age, sex, severity step and duration of the disease. 25
      hydroxyvitamin D was low in 8 of the 10 cases with osteopenia. Osteopenia was
      present in 7 children who were not under CSI, but have received multiple trials
      of oral corticoids for severe exacerbations. CONCLUSIONS: Osteopenia was present
      in 52% of children that were under inhaled corticoids for more than 12 months and
      it correlated with the duration of CSI, but not with the daily dose. Systemic
      corticoid use is a significant cause of osteopenia in asthmatic children.

PMID- 16607824
TI  - [Drug-induced dermatological pathology in renal transplantation patients].
AB  - The broad spectrum of muco-cutaneous manifestations of renal transplantation
      patients correlates mainly with immunosuppressive therapy. Our study refers to 56
      patients with renal transplantation (29 women and 27 men) followed up in the
      Dialysis and Renal Transplantation Center of Parhon University Hospital Iasi from
      November 2000 till October 2003. The most frequent muco-cutaneous manifestations
      were: infectious complications in 18 cases (32.1%), gum hyperplasia in 14
      cases(25%), acne in 11 cases (19.6%), skin hyperpigmentation in 7 cases (12.5%),
      oral candidiasis in 6 cases (10.7%), vascular fragility in 5 cases (8.9%),
      hypertrichosis in 5 cases (8.9%), itching in 3 cases (5.3%), facial erythema in 3
      cases (5.3%), full-moon facies in 3 cases (5.3%). These manifestations, often
      with unclear pathogenesis, are dose-related and almost unavoidable.

PMID- 16607825
TI  - [The influence of intermediate physical training on some non-enzyme antioxidants
      of oxidative stress, in moderate hypertension].
AB  - A group of patients with moderate hypertension (149-150/90-99 mm Hg) performed
      physical exercise for 3 months; we determined the oxidative stress in blood
      samples, by calculating the level of some biochemical markers, non-enzyme
      antioxidants, glutathione (GSH), total -SH groups (G-STH), nonprotein -SH groups
      (G-SHNP), their G-SHT/G-SHNP ratio, uric acid, malondialdehyde (MDA) and
      comparing the results with the values obtained from a group of healthy subjects.
      We found an increased oxidative stress at the HTA patients, with initial (Vi)
      decreasing values of GSH and uric acid, and with higher values of MDA. After the
      3 months (Vf) of physical training, the oxidative stress improved, with
      increasing GSH, uric acid and decreasing MDA, compared to normal subjects. The
      initial values of G-SHT, G-SHNP and their ratio, increased, but decreased after 3
      months, with an inverse aspect to GSH. The clinical study proved that after 3
      months of physical exercise, there wasn't any increased oxidative stress at the
      HTA patients; however, the oxidative stress is present, proved by the values of
      MDA, significantly higher compared to the normal subjects.

PMID- 16607826
TI  - [Cardiac amyloidosis. A case report].
AB  - The paper presents the morphoclinical picture in cardiac amyloidosis to a 50
      years old man admitted at Iasi Cardiology Center with progressive chronic cardiac
      failure, the patient having recent history of restrictive cardiomyopathy. It was
      made a complete cardiovascular evaluation including the right cardiac
      catheterization for endomyocardial biopsy. The biopsy specimens were fixed in
      buffered 10 % formalin, followed by routine paraffin embedding, and were stained
      with haematoxylin-eosin, elastic Van Gieson and sulphated blue Alcian for amyloid
      evaluation. The amyloid deposits were evidentiated in the interstitium and into
      vascular walls of the biopsy, pointing the importance of the morphological exam
      for amyloidosis diagnosis.

PMID- 16607827
TI  - [Considerations regarding one particular case of Rett syndrome].
AB  - Rett syndrome is a form of X-linked mental retardation limited to females,
      expressed by postnatal microcephaly, moderate/severe mental retardation and
      prominent autistic features. We present a case to illustrate this rare entity,
      but also to discuss the suggestive behaviour and to underline the importance of
      diagnostic criteria. Our case associates porencephaly and positive CMV test that
      raised diagnostic difficulties in the beginning.

PMID- 16607828
TI  - [Turner's syndrome, diagnosis and therapeutical approach].
AB  - Turner's Syndrome is a rare chromosomal disorder of females (1 : 2500)
      characterized by short stature and the lack of sexual development at puberty.
      Other physical features may include a webbed neck, heart defects, kidney
      abnormalities, and/or various other malformations. Diagnosis should be considered
      in individuals with primary or secondary amenorrhea and adult women with
      unexplained infertility, particularly when such individuals also are short in
      stature. In childhood, growth hormone therapy is standard to prevent short
      stature as an adult. Estrogen replacement therapy usually is required, but
      starting too early can compromise adult height. The most frequent, the
      possibility of a good diagnosis appears at puberty. The early diagnosis needs the
      karyotyping as screening method. The correct treatment, which is made on time,
      has a good mental and social life influence.

PMID- 16607830
TI  - [Breast conservative surgery].
AB  - Breast conservative therapy is considered an adequate therapeutical method for
      early stage breast cancer. Breast conservative treatment consists of partial
      mastectomy, axillary dissection and radiotherapy. Patient selection is based on
      clinical, histological and individual factors. The frozen sections examination
      provides prompt differentiation between benign/malign lesions and precise
      assessment of the oncologic margins of the specimen. Preoperative marking of
      nonpalpable breast lesion with hook wire represents a progress for breast
      conservative treatment. Sentinel lymph node biopsy represents an alternative to
      axillary dissection, in order to reduce subsequent morbidity.

PMID- 16607829
TI  - [Erysipelothrix rhusiopathiae--rare etiology of persistent febrile syndrome].
AB  - Erysipelothrix rhusiopathiae is a Gram-positive rod, carried by many domestic and
      pet animals and very resistant in the environmental habitat, causing an anthropo
      zoonosis infection in humans. It can determine, most frequently, a skin infection
      and may cause also septic arthritis or systemic infection, usually associated
      with aortic endocarditis. Bacteremia without endocarditis is a very rare
      presentation, generally seen in immunocompromised patients. We report such an
      unexpected diagnosis in a 75-years old woman, with mitral regurgitation, who was
      investigated for a persistent febrile syndrome, with no evidence of vegetation on
      repeated echo examinations and no evidence of the entry portal and who recovered
      successfully from an E. rhusiopathiae bacteremia with Ampicillin iv. therapy for
      14 days.

PMID- 16607831
TI  - [Differentiated thyroid cancer--staging and prognostic systems].
AB  - Differentiated thyroid cancer (DTC), including papillary and follicular carcinoma
      with histological variants, has an excellent prognosis; nevertheless a subset of
      these tumours is clinically aggressive and, in some patients, fatal. Treatment of
      DTC remains controversial, regarding the extent of primary surgical resection,
      the need for lymph node dissection and the role of postoperative radioactive
      iodine ablation. In addition to the widely accepted TNM classification,
      recognition of significant risk factors and developing of staging systems, such
      as AMES, AGES, MACIS, MSKCC and NTCTCS, has helped to identify the patients with
      a potential aggressive course of the disease and high risk of recurrence. This
      has allowed the development of a rational and selective approach to therapy,
      thus, avoiding excessive treatment and subsequent morbidity without compromising
      the oncological outcome.

PMID- 16607832
TI  - [Tailored surgical treatment for post-caustics stenosis of the upper digestive
      tract with complicated lesions. Clinical experience at our department in the last
      ten years].
AB  - The ingestion of caustic substances generates severe lesions of superior
      digestive tract, leading to stenosis in 50% of patients, of which almost 50% will
      require surgical treatment. A number of 29 patients with caustic lesions were
      treated in the IIIrd Surgical Unit from 1993 to 2004. The most frequent corrosive
      agent was a strong alkaline solution. The location of the post caustics
      strictures was esophageal in 18 cases, esophagogastric in 7 cases and laryngo
      pharyngo-esophageal in 4 cases. Surgical procedures consisted of 8
      esophagoplasties with ascending colon and ileum, 12 with left colon, 3 with
      transverse colon and splenic flexure, and in 5 cases transhiatal resection with
      cervical esophago-gastric anastomosis. 5 patients required gastric resections of
      variable extent, in addition to the esophageal reconstruction: antrectomy with
      trunk vagotomy--1 case, subtotal gastrectomy--3 cases and total gastrectomy--1
      case. In the group with pharyngeal lesions, esophageal reconstruction followed
      pharyngoplasty with cutaneous tube performed in the ENT department. Hospital
      mortality rate was 3,4 % (1 case). Postoperative morbidity of 20,6 % consisted of
      cervical anastomosis leakages in 2 cases and pleural effusions in 4 cases.
      Surgical treatment of the post caustics strictures of the upper digestive tract
      must be adapted to the location and severity of the lesions, requiring adequate
      operative experience and special pre- and postoperative care.

PMID- 16607833
TI  - [Bronchoscopy in thoracic trauma].
AB  - Thoracic trauma often bears difficult problems of diagnosis and treatment. This
      paper reports 87 procedures on 20 severe thoracic injured patients, who have also
      suffered multiple injuries, to whom was performed bronchoscopy. These cases were
      regarding gender, age, traumatic cause, associated injuries and dynamic endo
      bronchial aspect. There are detailed technique used in bronchoscopy and
      bronchoscopic suction, additional diagnostic procedures, technical tips,
      incidents and are also reported close and follow up results in these cases. We
      discuss indications of bronchoscopy and broncho-aspiration in thoracic trauma
      from diagnostic and treatment point of view. Conclusions underline major role of
      bronchoscopy in the management of severe thoracic trauma.

PMID- 16607834
TI  - [Paraclinical methods for the assessment of chronic rheumatic inflammatory
      processes].
AB  - Paraclinical methods and technics could be classified in biological, histologic
      and radiological investigation. Biological investigations are represented by:
      ESR, hemogram, count of leukocyte, investigation of bone marrow, CRP, fibrinogen,
      orosomucoid, cytokines etc.; histologic investigation of synovial fluid;
      arthroscopy; X-ray investigation (RMN, scintigraphy, CT).

PMID- 16607835
TI  - [Expression of stem cell markers on fetal and tumoral human liver cells in
      primary culture].
AB  - Hepatic stem cells can be identified by the expression of putative markers such
      as CD117 (c-kit), CD90 (Thy-1), CD34, and HLA-DR. We have identified populations
      expressing these markers in both fetal and tumoral human liver by flow cytometry,
      using monoclonal antibodies against CD90, CD117, CD34, and HLA-DR. In tumoral
      liver CD117+/CD90+ cells were found in decreasing number from the neoplastic
      (2.48 +/- 0.67) and peritumoral region (0.88 +/- 0.12) to the area of para
      tumoral (normal) parenchyma (0.13 +/- 0.04). The CD117+/CD34+ cells showed the
      following distribution: 0.35 +/- 0.05% in the tumoral region, 1.01 +/- 0.23% in
      the peritumoral region and 0.35 +/- 0.01 in the para-tumoral region. Using the
      same markers on fetal liver cells we have also identified small populations of
      CD117+/CD90+ cells (0.28 +/- 0.07%) and CD117+/CD34+ cells (1.13 +/- 0.24%),
      presumably resident stem cells or hematopoietic stem cells. Immunomagnetic
      negative separation was then performed on fetal liver cells using monoclonal
      antibodies against specific markers of hematopoietic lineages such as CD3, 14,
      16, 19, 22, and CD56 to eliminate this population. The remaining cells were then
      incubated with fluorescently labeled monoclonal antibodies against CD90 and CD117
      and analyzed using fluorescence microscopy. As expected these markers were
      expressed on the majority of the selected cells (89.28 +/- 9.56%). Isolation
      using appropriate markers and initiation of primary cultures is a first step to
      the therapeutic use of fetal stem cells and for the study of adult liver stem
      cells involvement in carcinogenesis.

PMID- 16607836
TI  - [Deletion of two genes from the genome of fission yeast Schizosaccharomyces
      pombe. Genetic manipulation and phenotype study].
AB  - The aim of this study was to delete two genes from the genome of the fission
      yeast S. pombe in order to search for their functions in the cell. These genes
      are SPAC869.02c (MRI) and SPBC21C3.19 (MR2) and previous studies reported their
      significant induction after gamma irradiation. We carried out the deletions of
      the two genes and we replaced them with the selection marker ura4. Among the
      phenotype characteristics we tested the viability, the sexual behaviour and the
      radiosensitivity to ultraviolet and gamma irradiation. Our results indicate that
      MR1-deleted strain is sensitive to both UV and gamma irradiation, while the
      survival of the irradiated MR2-deleted strain doesn't appear to be influenced by
      the deletion. This suggests an involvement of MR1 gene in the adaptive response
      triggered by these types of genotoxic aggression. The comparison of MR1-d and MR2
      d with the double deleted strains containing the deletion of MR1 or MR2 combined
      with the deletion of sty1 or rad3 genes led to a surprising result: the double
      mutants MR1-d sty1-d and MR1-d rad3-d were more resistant to both UV and gamma
      irradiation than the simple deleted strains sty1-d and rad3-d, respectively. This
      suggests a possible contribution of MR1 gene to the lethal process taking place
      in irradiated cells.

PMID- 16607837
TI  - [The origin and distribution of retro-pyelic artery].
AB  - We used as study methods of retro-pyelic artery: dissection on adult human bodies
      and on human fetuses, injection of plastic material followed by corrosion and the
      study of selective and total renal nephroangiography. We've studied the origin,
      the termination way and vascularization territory of retro-pyelic artery on 208
      cases. We found retro-pyelic artery origin to have 3 arterial sources: as
      terminal branch of renal artery (58.65%); from pre-pyelic artery (40.38%) and as
      supplementary renal artery from aorta (0.96%). Although, usually retro-pyelic
      artery trajectory is arcade like, we found this aspect in 38.46% cases. In 19.71%
      cases the trajectory has an italic "S" or double arcade aspect, in 31.73% cases,
      retro-pyelic artery is terminated by bifurcation, trifurcation in 9.13% cases and
      ramification in four branches in only 0.96% cases. Regardless of it's aspect, in
      most of the cases (31.73%), retro-pyelic artery branches vascularize the
      posterior half of the kidney, in 28.36% cases, just the posterior middle part of
      the kidney and in the remaining cases does not vascularize the superior pole
      (18.75%) or the inferior pole (21.15%).

PMID- 16607838
TI  - [The detection of dysplastic lesions of the gallbladder mucosa in polypoid
      cholelithiasis].
AB  - AIM: To investigate the hyperplastic and/or dysplastic lesions in the gallbladder
      mucosa. METHODS: We used the immunohistochemical Ardeleanu-Hsu-Bussolati and
      Gugliotta methods, with avidin and peroxide biotin, adapted in the laboratory of
      University Hospital "St. Spiridon" Iasi. There were studied ten cases of polypoid
      cholelithiasis, with the following markers: Ki67, PCNA, and p53. RESULTS: The
      immunohistochemical methods using Ki67, PCNA and p53 protein allowed the
      evaluation of the abnormal proliferation abilities characteristic for some
      hyperplastic or dysplastic lesions, found in our cases of cholelithiasis.
      CONCLUSIONS: The utilization of these markers permitted us to establish a good
      correlation between the high activity of Ki67 and the morphological aggression
      indicators in hyperplastic and dysplastic gallbladder epithelium. There is also a
      correlation between the percentage of the cells marked with anti-PCNA antibody
      and the existence of p53 protein in these lesions.

PMID- 16607839
TI  - [Population aging and public health. The active aging concept].
AB  - Population aging has been recognized as one of the most important human
      achievement, being the result of improved living conditions and medical advances.
      According to UN Projections, in the year 2025 there will be living in the world
      1.2 billion elderly people, and 71 % of them are likely to be in the developing
      countries. Between 1950 and 2025, the "Old" Old (those who are 80 years and
      above) will grow twice as fast as the 60-plus age group. In these conditions, we
      are confronted with two major issues: providing older people with opportunities
      for independence, health, productivity, and protection while at the same time
      maintaining economic prosperity in society. These two issues will require
      multiple economic, financial and social changes. The concept of quality of life
      is expressed in this large chapter about aging through active aging, which is
      depending on social and economic factors, personal and behavioural factors,
      health and social services, environment, gender and culture. The programmes for
      promoting active aging have to encourage healthy life styles, including healthy
      nutrition policies, active life and avoidance of chronic illnesses.

PMID- 16607840
TI  - [How protective is the immunization against viral hepatitis B prospectively?
      Seroprevalence study on viral hepatitis B infection].
AB  - Sero-epidemiological studies on herd immunity following the vaccination against
      hepatitis B virus may contribute to assess the needs and the optimal calendar of
      some booster vaccinations against hepatitis B. Such studies are quite uncommon.
      In order to evaluate the immune protection at community scale we performed a
      seroprevalence study using a sample of 360 volunteer subjects stratified in 9
      groups of age. Sterile sera were obtained and preserved as frozen at -20 degrees
      C, and antibodies against HBsAg were measured using ELISA kits made by Dia Sorin,
      Italy. Data base and statistical processing of data have been made using Access,
      Epi Info and Excel software. 60.3% of subjects proved having protective seric
      levels of Anti-HBs, significantly prevailing in female subjects (68.8% ; p <
      0,001) and in urban population (62.8%; p <0,001). The general trend of Anti-HBs
      by age varied insignificantly (correlation coefficient 0.6%); the values were
      significantly lower in the groups of 10-14 years of age (39.4%; p<0,001) and in
      15-19 years of age (40%; p<0,001). The serum levels of Anti-HBs varied between
      maximum a of 1.970 mUI/ml and a minimum of 1 mUI/ml, the geometric average being
      of 41 mUI/ml (standard deviation 27.3 ; IC 95% : (38.18-43.82)). The vaccine
      efficacy for the level considered as protective (10 mUI/ml) has been 81.9% (IC
      95% : (76.1-87.7)). The protection against hepatitis B viral infection assessed
      by measuring the prevalence of Anti-HBs is significantly more frequent in female
      subjects and in urban population. The trend of serum level of Anti-HBs by age,
      having irrelevant variations by age, has been induced by vaccination against
      hepatitis B virus starting 1995. The efficacy of vaccinations in newborns and
      health care personnel, in the field populations, was as high as 81.9%.

PMID- 16607841
TI  - [Epidemiologic research to assess some socioeconomic aspects of health care in
      patients with infections caused by group A beta hemolytic streptococcus and their
      complications].
AB  - Authors present some epidemiological aspects of medical and socioeconomic
      implications caused by group A beta hemolytic streptococcus (ABHS) infections and
      by their complications, assessed on 10948 inpatients with angina, 323 with
      scarlet fever, and 644 with erysipelas, hospitalized in the City of Galati,
      between 2000-2003. All these three major diseases determined by ABHS needed 79125
      days of hospitalization, with an average period of 6.4 days for angina, 76 for
      scarlet fever, and 10.4 for erysipelas. The costs of the mere hospitalization of
      these inpatients (11915) amounted to 14,479,543,800 lei. This fact highlights how
      costly the infections caused by AHBS are.

PMID- 16607842
TI  - [The impact of a sore throat score on clinical management of streptococcal
      angina].
AB  - OBJECTIVE: To establish the validity and the role of a clinical sore throat score
      in clinical management of streptococcal angina on a first visit to a primary care
      provider. METHODS: This study included 168 patients. The sore throat score had 5
      criteria: age, fever, absence of cough, tender anterior cervical nodes, tonsillar
      swelling or exudate. The score range is -1 to 5. RESULTS: Of the 168 patients, 53
      (31.5%) had a positive culture result for beta hemolytic streptococci. Compared
      with throat culture a score = 3 has a sensitivity of 62.,26% (95%CI: 47.9%
      75.2%), a specificity of 78.26% (95%CI: 69.6%-85.4%). Efficiency of this score is
      73.21%. CONCLUSIONS: The clinical sore throat score may assist the primary care
      providers in estimating that a patient has streptococcal angina without replacing
      rapid antigenic testing or culture.

PMID- 16607843
TI  - [Epidemiologic and laboratory assessments of etiologic implications of
      Blastocystis hominis in gastrointestinal diseases].
AB  - Authors present the first laboratory and epidemiological results which reveal the
      circulation in a population of protozoan Blastocystis hominis and its implication
      in the determinations of some gastrointestinal troubles, with fever, diarrhea and
      constipation, intense intestinal meteorism, associated with abdominal pain and
      cramps. Out of the 3106 investigated patients, 9.7% presented B. hominis as a
      unique etiologic agent, with an increased prevalence in adults (74.3%) and women
      (65.3%). Blastocystis infection with clinical manifestations or its asymptomatic
      form is included among emergent diseases.

PMID- 16607845
TI  - [Epidemiological and clinical research on arthrosis and other rheumatic diseases
      recorded in Braila district, between 1994-2003].
AB  - Authors present the results of the epidemiological and clinical research carried
      out in Braila district, between 1994-2003. They revealed that arthrosis recorded
      113.4-254.9%000 yearly, involving over 1/3 out of the health care request in
      patients over 70 years old. Medical and economical implications were assessed by
      the analysis of annual evolution of patients' consultations, hospitalizations,
      discharges and temporary work incapacity days for osteoarticular diseases, in
      general, and arthroses, in particular.

PMID- 16607844
TI  - [Descriptive epidemiologic study of nosocomial infections in "C.I. Parhon"
      hospital of Iasi].
AB  - Nosocomial infections (NI) represent a major public health problem. The
      descriptive study was carried out during one year, based on a lot of 12,731 in
      patients from "C.I. Parhon" hospital. The objectives of the study were assessment
      of NI incidence and risk factors as well as monitoring resistance to
      antimicrobial drugs of bacterial pathogens from the hospital. The results of the
      study show lower NI incidence rates: 0.27%, most of them (91.5%) being urinary
      tract infections in the age group 65 y and over. 42.8% of cases were associated
      with risk factor of diabetes mellitus, neoplasm, skin or cardiovascular chronic
      conditions. The main etiological agent found for the NI was pseudomonas pyocyanea
      resistant to antibiotics. The antibiotic sensitivity analysis for the other gram
      negative rods illustrates gradually acquired resistance to the third or fourth
      generation of cephalosporins.

PMID- 16607846
TI  - [Specifics of food intake by schoolchildren in the rural areas of Moldova].
AB  - 149 schoolchildren, 14-15 years old, from 4 rural communities pending on 4
      different Moldova counties have been investigated using the one day questionnaire
      technique. From the entire studied group, only 7.4% are do not eat breakfast
      before attending school. 35.5% of the schoolchildren consider their sugar intake
      to be excessive, without taking into account the sugar major role in nervous cell
      function. The average daily intake for fresh fruits, vegetables and milk is in
      most cases adequate, but significant differences are present between the
      communities, related with the socio-economic status of the families and, also,
      with nutritional.

PMID- 16607847
TI  - [The value of radical surgical treatment in benign symmetric lipomatosis].
AB  - Benign symmetric lipomatosis (BSL) is a rare proliferative disorder of the
      adipose tissue, characterized by symmetrical fat deposits, predominantly in the
      neck and shoulder area, upper back and arms. This study contains the analyse of a
      lot of ten patients with BSL, which were surgical treated in our department
      between 1994-2004. The followed parameters were: sex, age, heredo-collateral
      antecedents, associated organic diseases, the motivation of medical
      addressability, the sites of first lesions, the length of evolution before the
      admission, methods for diagnosis, number of surgical sessions necessary to
      extirpation of fat deposits, the results of the periodic follow-up examination.
      The followed patients with BSL were treated by surgery (extirpation of the
      cervical fat masses): one surgical session (8 cases) or two sessions (2 cases).
      The morphological, functional and psychic results were good. Recurrence at the
      site of surgery was not detected in any follow-up subjects. The elective
      treatment in BSL is surgical, by extirpation of the lipomatous masses; a
      satisfactory, lasting result can be expected only after the most radical possible
      extirpation (not only for cosmetic intentions).

PMID- 16607848
TI  - [Acinic cell adenocarcinoma of the lip].
AB  - The variable histological appearance of acinic cell carcinoma coupled with its
      uncommon occurrence account for considerable diagnostic difficulties. We present
      the case of a 68 years old women, with a salivary cyst localised in the upper
      lip. The tumour mass was excised, fixed in formaline, embedded in paraffin and
      the sections were stained with Haematoxylin-Eosin, PAS-Haematoxylin, PAS-Alcian
      blue and Perls. The tumour was nodular, well circumscribed, with a cystic
      appearance on the cut surface. Microscopically, the tumour had a papillary-cystic
      growth, with one large cystic space lined by epithelium of variable thickness and
      branching projections of epithelium occupying a large portion of the cyst's
      lumen. Different cellular features were recognised in the tumour, with the
      presence of both serous and mucous acinar differentiation. Also, vacuolated cells
      were present in a large number. Acinic cell adenocarcinoma is a malignant
      epithelial neoplasm in which the neoplastic cells demonstrate not only serous
      acinar differentiation. The clinical and histopathological findings are discussed
      in the light of the literature.

PMID- 16607849
TI  - [Oral manifestations during herpes virus infection. Case report].
AB  - The infections due to herpes viruses are widely spread, people being every day at
      high risk of contamination starting early age. The characteristic of the herpes
      virus infection consists of a symptom less evolution following the prime
      infection. As for any other herpetic infection, episodes infection exacerbation
      is due to some determining factors. Clinical symptom in herpes virus infection
      varies according to the virus type, age of the patient and site. Oral signs and
      symptoms are numerous, extremely intense and often, difficult to diagnose.
      Progressing in so many ways and being diagnosed and treated by so many medical
      specialties it is difficult to evaluate the actual number of cases. Consequently
      it is mandatory to train dentists in order to be able to accurately diagnose and
      treat the herpetic infection and to prevent nosocomial cross infections in dental
      office.

PMID- 16607850
TI  - Preliminary HPLC study on some polyphenols of Geranium robertianum L.
      (Geraniaceae).
AB  - In order to continue our previous studies concerning Geranium robertianum L.,
      herb Robert (Geraniaceae), we have realised a HPLC study of some polyphenols
      using an original method created by a group of young researchers from the
      University of Medicine and Pharmacy of Cluj-Napoca. We have identified and
      measured in the dried Geranii robertiani herba (harvested from Valea Runcului,
      district of Alba-Iulia) the following compounds: hyperoside (3.64 microg/100 mg),
      ellagic acid (7599.76 microg/100 mg), isoquercitrin (49.49 microg/100 mg),
      quercetrin (83.92 microg/100 mg), kaempferols (143.43 microg/100 mg), caftaric
      acid (166.92 microg/100 mg), rutoside (72.23 microg/100 mg). We have also
      analysed a hydrolysed sample of the same drug in which we have identified and
      measured: caffeic acid (6.62 microg/100 mg), ellagic acid (10550.65 microg/100
      mg), quercetrin (203.44 microg/100 mg), kaempferols (231.80 microg/100 mg),
      caftaric acid (47.41 microg/100 mg). We have indirectly proved the presence of
      ellagic tannins (the amount of ellagic acid increases after acid hydrolise) and
      the existence of bi- or polycaffeoil derivatives (the caffeic acid is present
      only in the hydrolysed sample). The flavonoid aglycones exist in both forms: as
      free compounds and as part of the flavonoid molecules.

PMID- 16607851
TI  - A comparative study regarding the morphological alteration on the gastric level
      after the administration of piroxicam and complexes with bio-ions Cu(II), Co(II),
      Zn(II) to rats.
AB  - The complex combinations of Piroxicam (Pirox) with the metallic bio-ions: Cu(II),
      Co(II), Zn(II) have been obtained and defined in a previous stage by physical
      chemical methods (IR, X, SM, CSS-UV, DTA, DTG), an toxicological and biochemical
      aspect. In this research are presented the results of the histological
      examinations at the level of stomach, for each compound, at 24 hours and at 7
      days after the administration of the Piroxicam and of its complexes to rats. The
      tissues histo-pathological investigation has pointed out lesions the glandular
      stomach level (necrosis, ulcers) especially after the administration of the
      Piroxicam and of the Zn-Pirox complex. Name of these have been present after the
      administration of Cu-Pirox, Co-Pirox.

PMID- 16607852
TI  - [Meropenem activity against staphylococci].
AB  - Meropenem is a new carbapenem with excellent activity against different Gram
      negative and Gram-positive bacteria. Its good antibacterial activity is closely
      related to high hydrolysis resistance by bacterial beta-lactamases. The aim of
      this study was to evaluate antimicrobial activity of meropenem by comparison that
      of oxacillin, gentamicin, clarithromycin and ciprofloxacin against 458
      staphylococci collected during 2004 period from healthy individuals. Minimum
      inhibitory concentrations were determined by agar dilution technique. Meropenem
      has an activity clearly superior to the other tested agents. Resistance rate is
      zero for all investigated strains.

PMID- 16607853
TI  - [Residual stress evaluation].
AB  - Paper presents the results of an international research project carried out by
      author in the laboratories of the University of Pisa, Italy and funded by NATO.
      Research showed the feasibility of the measurement of residual stress up to 90%
      of the material yields strength using a four gages rosette and analytical
      relations. This new method can be used with an improved accuracy in residual
      stress measurements in bones, prosthesis and implants.

PMID- 16607854
TI  - [Functional characteristics of nucleotide-receptors in human neutrophils].
AB  - Nucleotides are important extracellular signaling molecules. It has been
      established that nucleotides are released from damaged cells, activated platelets
      and endothelial cells. Thus, at the site of vascular injury, the concentrations
      of extracellular nucleotides can become elevated. Nucleotides have been shown to
      cause mobilization of intracellular calcium, upregulation of Mac-1 (CD11b/CD18),
      degranulation, and chemotaxis in human neutrophils. The goal of this work is to
      investigate the functional characteristics of nucleotide-receptors in human
      neutrophils. Nucleotides (ATP and UTP), caused intracellular calcium mobilization
      in a dose dependent manner. Pharmacological characterization using selective
      agonists (ATP, UTP), pertussis toxin in human neutrophils and human astrocytoma
      cells 1321N1 stably expressing P2Y2 or P2Y4 receptors, revealed that human
      neutrophils express only functional P2Y2 receptors. Treatment of neutrophils with
      pertussis toxin causes a partial inhibition of nucleotide-induced calcium
      mobilization. Similarly, by using 1321N astrocytoma cells expressing the P2Y2
      receptor we confirmed that calcium mobilization is only partially inhibited by
      pertussis toxin. The partial resistance of P2Y2-mediated intracellular calcium
      mobilization suggests that this receptor subtype is coupled not only to a Gi
      protein, but also to a protein belonging to the Gq-family (most likely G16). In
      conclusion, we have shown that human neutrophils express functional P2Y2
      receptors and all the nucleotide responses are mediated by P2Y2 receptor subtype
      and that P2Y2 receptors are the functional able to trigger intracellular
      signaling event in human neutrophils through dual activation of different G
      proteins.

PMID- 16607856
TI  - [Risk of cardiac complications in patients undergoing major vascular surgery].
AB  - In patients undergoing major vascular surgery cardiac complications are the major
      cause of perioperative morbidity and mortality. This is related to the frequent
      presence of underlying coronary artery disease. The aim of the preoperative
      cardiac risk assessment is to evaluate the presence and degree of coronary artery
      disease along with other risk factors such as cerebrovascular disease, renal
      insufficiency, and diabetes mellitus that may influence the perioperative risk of
      these patients. Based on the presence and number of cardiac risk factors the
      individual risk profile can be determined, which may facilitate medical decision
      making about the perioperative and long-term management of these patients. In the
      present review based on data from current literature we summarized the pathology
      of perioperative cardiac complications, and the role of cardiac risk assessment
      and risk reduction strategies in patients undergoing major vascular surgery. In
      this review the authors summarized data from current literature and found that a
      limited set of risk factors and a result of a noninvasive test used for detection
      of coronary artery disease may help to stratify patients into low-, intermediate-
      and high risk for perioperative cardiac complications. If patients with
      intermediate- to high-risk prescribed beta-blockers the risk of cardiac
      complications can be reduced. Along with beta-blockers it was also found that
      perioperative use of statins may also help to reduce the risk of cardiac
      complications. In patients identified to be at very high-risk further
      perioperative evaluation and management should include coronary angiography with
      subsequent coronary revascularization if there is a clearly defined need,
      independent of the need for vascular surgery.

PMID- 16607855
TI  - [Ionic calcium and magnesium from pharmaceutical product BEROCCA effects on
      neuromuscular excitability].
AB  - The important physiological role of calcium and magnesium ions is all over
      recognised, about a lot of enzymatic reactions. Magnesium deficit produce
      neuromuscular hyper-reactivity, psychic reactions, functional hypoparathyroidism,
      increase of K+ channels membranes permeability, while hypermagnesemia decrease
      Ach release from neuromuscular synapsis, with post-synaptic excitability
      decreasing. Using BEROCCA (Hoffman la Roche) 1 cp/day, 30 days at the teenagers
      with behaviour troubles and at a goup of pregnant women (trimester I-III) with
      paresthesia, irritability, sleeplessness, we observed an improve of clinical
      signs, increasing plasma Ca2+ and Mg2+. EEG and EMG prove the beneficial effects
      of pharmaceutical product BEROCCA.

PMID- 16607857
TI  - [Effect of cigarette smoking on bone quality parameters in women].
AB  - INTRODUCTION: Smoking is a risk factor for osteoporosis. In a previous study, the
      authors showed lower bone density among smokers in a group of postmenopausal
      women. AIMS: After this finding, the primary goal of current research was to
      investigate how smoking could influence bone quality. METHODS: Forty-five (age
      range: 25-72 ys) smoker women were compared with 45 nonsmoker women adjusted for
      age and anthropometric parameters. Quantitative ultrasound method was used to
      determine the speed of ultrasound and the ultrasound attenuation transmitting the
      left heel (Achilles In Sight, GE Lunar). Dual photon absorptiometry method was
      applied to investigate the bone mineral density of lumbar spine and left femoral
      neck (Prodigy, GE Lunar) and single photon absorptiometry was used to determine
      the bone mineral content of radius at the non dominant side (NK-364, Gamma).
      RESULTS: No difference was found between smokers and non-smokers among the
      premenopausal group, however, postmenopausal smoker women had slightly lower
      speed of ultrasound and ultrasound attenuation values than non-smoker women.
      Postmenopausal smoker women suffering from bone fracture had significantly lower
      speed of ultrasound than postmenopausal non-smoker women (1508.9 vs. 1525.3 m/s,
      respectively), despite their bone density did not differ from each other.
      CONCLUSION: These data augment the knowledge about the injurious effect of
      smoking. The increased risk for bone fracture among smokers could be explained
      not only with the decrease of bone mass, which was previously described, but also
      with a decreased bone elasticity.

PMID- 16607858
TI  - [Diagnostic and therapeutic use of endoscopic resection of gastric mucosa].
AB  - BACKGROUND: EMR is a widely used treatment option for gastric adenoma and early
      gastric cancer, but, there are no data on its use in Hungary. The aim of this
      study was to assess the diagnostic and therapeutic efficacy of EMR. PATIENTS: 44
      patients (30 females, 14 males, mean age: 67 years) were studied between 1994 and
      2005; 33 had severe concomitant diseases (liver cirrhosis or severe
      cardiovascular disease). Indigo carmine dye staining and electronic magnification
      was used in all cases, with endoscopic ultrasonography when indicated. 56 EMR-s
      were performed. The histological results on the biopsy and resected specimens
      were analyzed. RESULTS: The morphology of the lesions was type I in 20, type IIa
      in 35, and type IIa-IIc in 1 case. The diagnosis at first biopsy was in situ
      carcinoma in 3, adenoma with no dysplasia in 19, adenoma with low-grade dysplasia
      in 2, adenoma with moderate-grade dysplasia in 6, adenoma with high-grade
      dysplasia in 7, and hyperplastic lesion in 17 cases. The histology of EMR
      revealed in situ carcinoma in 5, carcinoid in 1, gastrointestinal stromal tumor
      in 1, adenoma with no dysplasia in 14, adenoma with low-grade dysplasia in 3,
      adenoma with moderate-grade dysplasia in 9, adenoma with high-grade dysplasia in
      1, hyperplastic lesion in 21, and no diagnosis in 1 case. However, the moderate-
      and high-grade dysplasia was diagnosed in different cases with the two methods.
      EMR was considered complete in all but 1 case. A Nd YAG laser was used in this
      patient with in situ carcinoma, where the resection margin was not free of cancer
      cells. Bleeding occurred in 3 cases; 1 required transfusion and had pneumonia
      postoperatively. There were no gastric cancer-related deaths during the median
      follow-up of 33 (1-90) months. In the follow up period we could not observe
      gastric malignancy in the previously hyperplastic polyp cases. Among adenoma
      cases one recurrence was seen in the same place and one in another location. One
      hyperplastic residuum occurred and in one case adenoma has grown in the same
      place. CONCLUSION: EMR, a facile and useful diagnostic and therapeutic technique,
      appears very safe in terms of complications even in patients with comorbidities.
      Biopsy is generally unreliable to diagnose gastric adenoma. Lesions should be
      fully resected by EMR for a final diagnosis and (depending on the lesion size and
      type) possibly definitive treatment.

PMID- 16607859
TI  - [Paradigms of fetal ethology].
AB  - In utero, the fetus is protected against biological and social influences of the
      outside world. This circumstance offers an opportunity for sonographic
      investigation of inherited fetal behavior free of extraneous effects. Observation
      of fetal activities with ultrasound permits the recognition of certain uniform
      features of fetal behavior. Immediately after birth, the neonate continues
      repeating those activities that he/she became accustomed to in the womb. Later
      these become modified by environmental influences. Nonetheless, basic inherited
      behavioral characteristics continue to be expressed and may remain recognizable
      even during adulthood. Some aspects of adult behavior may derive from experience
      acquired during fetal life. These include the hand-face reflex, various types of
      facial expression, such as smiling, crying, yawning, grimaces of dissatification
      and desperation as well as sticking out one's tongue.

PMID- 16607860
TI  - [The role of family therapy in the treatment of extremely severe anorexia
      nervosa].
AB  - The authors present the case of a fifteen-year-old anorectic girl. Her lowest
      body weight was after admission 16.5 kg, with a height of 139 cm-s (body mass
      index: 8.54 kg/m2). After five-year long unsuccessful individual therapy family
      therapy was administered, which caused remission, ascertained by a five-year
      follow-up. The authors stress that in the treatment of a subgroup of anorectic
      patients the family therapy could be a crucial therapeutical modality.

PMID- 16607861
TI  - Influence of location of acceleration sensor on physiological tremor of upper
      limb.
AB  - The physiological tremor of the upper limb in three positions of pronation,
      neutrality, and supination due to the movement of forearm was measured on four
      locations at the tip of the finger, the root of the finger in the hand, the
      wrist, and the elbow with use of an accelerated sensor. The evaluation of the
      total power, which was the summation of the power spectrum in the frequency range
      from 1 to 50 Hz, showed no significant difference in any of the positions. The
      maintenance of the upper limb at the horizontal level showed the coordination of
      the central nervous system due to the body parts of the upper arm, forearm, hand,
      and finger connected by the joint. The coherence spectra showed clear activation
      of the joint of the wrist in the main peak frequency of around 2.5 and 12.5 Hz in
      their respective positions. The value of the correlation coefficient in the
      location between the hand and finger was the largest at over 0.8, and those of
      the locations which connected the joint of the wrist between the forearm and hand
      and between the forearm and finger were significantly large with a value from 0.6
      to 0.8. The mean time (i.e., arrival time) of the transmission from the proximal
      side (i.e., upper arm and forearm) to the distal side (i.e., hand and finger) in
      the upper limb was evaluated quantitatively to be 20 ms for pronation and
      supination, but the value was small for neutrality.

PMID- 16607862
TI  - Neuromyotonia with neuropathy and muscle hypertrophy: association or cause?
AB  - Continuous muscle fibre activity in a patient with demyelinating neuropathy is
      rare. We report an 18 year old boy who presented with walking difficulty and
      continuous rippling in muscles of upper and lower limbs. He had dysarthric
      speech, hypertrophied arm and calf muscles with normal power, tone, reflexes and
      sensations. Myokymic discharges were seen in deltoid, biceps, quadriceps and calf
      muscles. His blood counts, chemistry, thyroid profile, DNA, Rh factor were normal
      and CPK was raised. CSF showed protein 50 mg/dl and 4 lymphocyte/mm3. Nerve
      conduction study revealed conduction block and absence of peroneal F wave. EMG
      showed neuromyotonic discharges which disappeared on regional neuromuscular
      blocker but not on nerve block or general anaesthesia. He responded partially to
      prednisolone. Acquired demyelinating neuropathy may result in neuromyotonia and
      muscle hypertrophy which may partially respond to prednisolone.

PMID- 16607863
TI  - Possibility of clinical application of tremor in the upper limb.
AB  - A procedure to evaluate the function of the glenohumeral joint (i.e., shoulder
      joint) for persons with shoulder disorders was proposed by analyzing tremor. In
      order to compare subjects with shoulder disorders to healthy subjects without
      disorders, characteristics of tremor for the healthy persons under various angles
      of glenohumeral joint and under the dominant and no-dominant sides of the upper
      limb were obtained by peak frequency and power spectrum as basic data. As for the
      persons with rotator cuff injury, the ratio of total powers for the affected side
      and the healthy side was obtained as the affective side ratio. The ratio showed
      the characteristic of the persons with the disorder, and discriminated the total
      power spectra of persons who were healthy and those with disorders.

PMID- 16607864
TI  - Electromyographical study of the pectoralis major (sternocostal part) and deltoid
      muscles (middle fibers) in volleyball sequential actions.
AB  - The Pectoralis Major muscles (Sternocostal part) and Deltoid (middle fibers) had
      been studied using electromyography in 8 male individuals, who practice
      volleyball, youth category, (age between 15 and 17 average +/- 16,25 years old),
      right-handed, those involved in volleyball for about one year. The objective was
      to analyze the potential of action of these muscles engaged in the volleyball
      movements: service, spike, pass, set and blocking with and without ball. The work
      was developed in the Electromyography and Biomechanics of Posture
      Laboratory(Physical Education Faculty--State University of Campinas--UNICAMP). To
      caption the muscle action potential, surface electrodes were set with conductive
      gel and fixed on the skin, in the center of the muscles. It was used an
      electromyography Lynx with 6 channels. The apparatus calibration was 2.500
      microV, 1199.760 Hz. The low and high pass filter was set at 600-10 Hz. The
      sequential experiments without ball were performed for 10 seconds, and the
      sequential experiments with ball in 12 seconds. RESULTS: The Pectoralis Major
      muscle (Sternocostal part) revealed active during the basic movements of
      volleyball, (service and spike) in all movements of the extension of the arm, as
      well as the arm abduction during the pass movement. The Deltoid muscle (middle
      fibers), in spite of being primary in the abduction, showed the potential of
      action in all movements practiced in volleyball, however, they were more intense,
      in the spike and block actions. It is interesting to observe, that the general
      average and the standard deviation of the Deltoid muscle (middle fibers), were
      higher in the sequential movements executed without ball.

PMID- 16607865
TI  - Dynamic and isometric protocols of knee extension: effect of fatigue on the EMG
      signal.
AB  - The objective of this study was to analyze the electromyographic (EMG) signal
      behavior of rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL) and
      biceps femoris (caput longum) (BFCL) from nine women during fatiguing dynamic and
      isometric knee extensions tests and to determine their EMGFT (Electromyographic
      Fatigue Threshold). Surface electrodes, biological signal acquisition module,
      analogical-digital converter board and specific software were used. The RMS (Root
      Mean Square) values obtained from concentric phase (80 to 30 degrees) of the
      dynamic knee extension and from isometric contraction were correlated with time
      on each load by linear regression analysis. The respective slopes were correlated
      with the correspondent load to determine the EMGFT. Force (Kgf) and median
      frequency--MF (Hz) obtained during MIVC (Maximal Isometric Voluntary Contraction)
      performed before and after the fatiguing tests were calculated in Matlab
      environment. The results demonstrated that the endurance time decreases with
      higher loads, the EMG amplitude increase with time and was greater at higher
      loads, between muscles in dynamic exercise the RF and VL showed higher slopes,
      and in isometric exercise the VL showed the same behavior. The EMGFT values were
      similar in both exercises; the force values predominantly decreased after
      fatiguing tests; however the MF only decreased after some loads. The protocols
      proposed allowed standardizing protocols at least to induce the fatigue process
      and to determine the EMGFT as an endurance indicative, which may be used to
      evaluate the effectiveness of rehabilitative or training interventions indicated
      to reduce muscle weakness and fatigue.

PMID- 16607866
TI  - BERA in children with hearing loss and delayed speech.
AB  - OBJECTIVES: The brainstem evoked response audiometry (BERA) is an objective
      neurophysiological method for the evaluation of the hearing threshold and
      diagnosing retrocochlear lesions. The aim of the study was to investigate the
      hearing level in children with suspected hearing loss or pathological speech
      development. PATIENTS AND METHODS: The BERA diagnostic procedure was applied in
      184 children ranging from 1 to 12 years of age at Ahmadi Hospital in Kuwait.
      RESULTS: We found profound hearing loss (deafness) in 13 children, severe hearing
      loss in 8 children, moderate hearing loss in 34 children, mild hearing loss in 34
      children, and normal hearing level in 95 children. Out of the children suspected
      for hearing loss, 42% actually had some level (mild-moderate) of hearing loss.
      Out of the children with delayed speech, 63% had some level (mild-profound) of
      hearing loss which actually caused the delay in speech development; 37% had
      normal hearing, but inadequate verbal communication affected their language
      acquisition and speech development. CONCLUSIONS: These results illustrate the
      necessity to test children hearing even with the slightest suspicion by the
      parent or doctor of hearing loss. The results warrant the establishment of a
      hearing screening test of newborns in Kuwait to provide hearing aid to children
      with hearing loss.

PMID- 16607867
TI  - Stabilization of lumbo-pelvic region and electromyography of the abdominal
      muscles.
AB  - It is usual to find athletes that can perform de curl up test easily, but are
      unable to maintain the stabilization of the low back during the double straight
      leg lowering (DSLL). In spite of having strong abdominal muscles, its
      stabilization role seems not to be effective. Thus, the purpose of this study was
      to verify the relation among individuals with strong abdominal muscles and: the
      ability in perform posterior pelvic tilt (PPT); the ability to stabilize the low
      back during the DSLL and the eletromyographic activity of the abdominal muscles.
      Eighteen male subjects (aged 19.27 +/- 3.5), without history of muscle skeletal
      dysfunction, performed both the PPT and DSLL tests. During these tests
      electromyographic signals of the rectus abdominis (RA), obliquus internus
      abdominis (OI) and obliquus externus abdominis (OE) were recorded, the angle of
      the hip and the pressure under the low back were measured. The results of
      analyses of variance (ANOVA) show that most volunteers accomplished the PPT test,
      actively flattening the low back with regular or good quality. However, none of
      them was able to stabilize the low back during the DSLL test. During the PPT test
      all abdominal muscle portions analysed were activated without significant
      differences. In an attempt of maintaining the lumbo-pelvic region stabilized
      during the DSLL, it was observed a tendency of higher bilateral activation of OE
      when compared to RA and OI muscle portions between 70 and 20 degrees of hip
      flexion.

PMID- 16607868
TI  - Prevalence and distribution of peripheral nerve injuries in victims of Bam
      earthquake.
AB  - INTRODUCTION: In the early morning of Friday 25th Dec. 2003, the ancient and
      historical city of Bam in Southern East of Iran was vibrated by a big and
      horrible earthquake for 6.4 degree of Richter. About 30,000 people were died and
      about 30,000 victims and injured persons were the initial results of the
      earthquake. Almost all of the buildings were destroyed and all the people became
      houseless. In this study, 156 patients with peripheral nerve lesion (PNL) were
      assessed for their injuries. MATERIALS AND METHODS: In a cross sectional study
      since the second week after the quake until 6 months later, we examined 506
      patients with the symptoms and signs of motor/sensory and performed the
      Electrodiagnostic study for all of the patients who had obvious or suspected
      lesion of peripheral nerves. There were 156 patients (31.2%) afflicted with
      peripheral nerve lesion. We performed NCS/EMG for upper limb and face at least 2
      weeks and for lower limb, at least 3 weeks after injury in 156 of the victims
      that had PNL. FINDINGS: Of 156 patients, 75 (48%) were female and 81 (52%) were
      male. The average of age was 29.2 +/- 12.9 years, about 87.2% were between 15 to
      50 yrs old. The frequency of injuries was 88 nerves, 53 neural plexuses and 5
      cauda equina lesions. The most frequent injured nerve was sciatic nerve (24.8%)
      and the next was Radial nerve (15.5%) and the less frequent nerve was axillary
      which observed just in 1 patient. 21.6% of patients had the brachial plexus
      and/or lumbosacral plexus injuries. There were more involvements in lower limbs
      comparing upper limbs and face (p < 0.01). CONCLUSION: Peripheral nerve injury is
      one of the most frequent injuries in earthquake victims. These lesions may cause
      temporary or lifelong disabilities in patients. In this study, the more frequent
      involvement of sciatic and radial nerve seems to be related to their anatomic
      location and also the position of victims when earthquake happened and the
      involvement of brachial and lumbosacral plexus could be due to inappropriate
      evacuation of the victims from the loads and also due to incorrect
      transportation.

PMID- 16607869
TI  - A practical approach to 64-slice coronary CT angiography.
AB  - Coronary computed tomography angiography with 64-slice multidetector CT scanners
      allows reproducible and accurate non-invasive evaluation of coronary
      atherosclerotic disease in most patients. These coronary CT angiography studies
      are very promising and exciting. However, the start-up phase of such a coronary
      CTA program can be challenging. We discuss the problems that one can encounter
      during start up of such a coronary CTA program and possible solutions. Training
      of the technologist, time-management and communication with the referring
      physician are key aspects of a successful coronary CTA program.

PMID- 16607870
TI  - Assessment of the appropriateness of requested radiological examinations for
      outpatients and the potential financial consequences of guideline application.
AB  - The purpose of this study was to evaluate whether requested radiological
      examinations for referred outpatients are in concordance with the guidelines as
      proposed by the consilium radiologicum. A second purpose was to evaluate the
      financial effect of strict guideline application. The radiological requests for
      1000 referrals were evaluated by 2 radiologists. A consensus score of 74.4%
      guideline conformity was reached. A mean save of 9.5 Euro per patient was
      calculated after strict guideline application. It is concluded that guidelines
      are a valuable tool for patient management in referring for radiological
      examinations and have a substantial effect on the available budget. Further
      improvements and fine-tuning of the guidelines are mandatory to increase their
      validity.

PMID- 16607871
TI  - Axe fragment pulmonary embolism. Interest of enhanced multislice helical CT with
      cardiac synchronised acquisitions.
AB  - A case of pulmonary embolism by an axe fragment investigated with enhanced mdCT
      with cardiac synchronised acquisitions is described. The authors stress the
      advantages of the techniques versus angiography for the exploration of foreign
      body pulmonary artery embolism.

PMID- 16607872
TI  - Congenital bilateral perisylvian syndrome: MR findings.
AB  - The insula of Reil is seen on every MR imaging study of the brain. It is
      interesting to be familiar with the insular anatomy, as the insula is often
      involved in brain pathology and it is a location in the brain with multiple vital
      functions, such as gustatory sensation, motor planning of speech, vestibular
      function, and cardiovascular para/orthosympathetic balance. We describe the
      anatomy of the insula and correlate the anatomy on MR imaging obtained at 1.5T.
      We illustrate the clinical importance of the insula by a case report.

PMID- 16607874
TI  - Conventional dental radiology: what the general radiologist needs to know.
AB  - This article aims to provide an overview of intraoral and orthopantomographic
      radiographs, including technique, indications, artefacts, relevant anatomy,
      current notation and common dental pathology. The normal anatomy is emphasised,
      because it is required for effective radiographic interpretation. Dental
      pathology, i.e. caries, periodontal disease, periapical inflammatory lesions and
      dental anomalies are illustrated.

PMID- 16607873
TI  - On the role of radiologists in the Belgian PROject on CAncer of the REctum,
      PROCARE.
AB  - Radiologists are involved at all stages of the treatment of patients with rectum
      cancer: in the preoperative staging, in the diagnosis of postoperative
      complications, in the detection of recurrent or metastatic disease during follow
      up, in the monitoring of the therapeutic effect of palliative therapy. PROCARE is
      a Belgian national project to improve outcome in all patients with rectum cancer.
      Guidelines were made by a multidisciplinary workgroup and are available on the
      web. Decentralised implementation of guidelines is organised by the scientific
      and professional organisations. It is planned that a central review committee of
      radiologists, delegated by the Royal Belgian Society of Radiology, will survey
      the quality of preoperative staging. Overall quality of care will be assured by
      registration in a specific national database starting in 2006. Participating
      teams will receive annual feedback. Radiologists should provide data on cTNM
      staging and cCRM. Differentiation between cT2 and cT3, cN0 and cN+, and
      measurement of the cCRM in mm are crucial as they have a relevant impact on
      treatment strategy. While spiral abdominal CT is adequate for cM staging, high
      resolution MRI is highly recommended and, in fact, a necessity for locoregional
      staging because its adequacy is superior to that of CT-scan and EUS. However, EUS
      is mandatory when local excision is considered, i.e. for cT1N0 lesions.

PMID- 16607875
TI  - The role of dental CT imaging in dental implantology.
AB  - The jaw has traditionally been evaluated by dentists and oral surgeons using
      conventional panoramic and intraoral films. During the past decade, dental
      computed tomography (CT) has become the method of choice for preimplantation
      assessment of jaw anatomy. This has urged the radiologist to take a more active
      role in evaluating the jaw. The aim of this article is to provide the reader with
      knowledge that should facilitate him to evaluate implant sites, dental related
      inflammatory diseases and augmentation procedures on dental CT scans.

PMID- 16607876
TI  - Imaging approach for differential diagnosis of jaw lesions: a quick reference
      guide.
AB  - The radiologists will be frequently consulted to evaluate a variety of
      maxillomandibular lesions or may incidentally encounter these lesions on routine
      plain films, computed tomography (CT) or magnetic resonance (MR) studies. This
      article provides the reader a diagnostic approach pattern when confronted with an
      unknown jaw lesion. The radiologic analysis for differential diagnosis primarily
      depends on specific cardinal and additional radiographic criteria on plain film
      studies. Cardinal radiographic criteria include the density of the lesion and the
      location with regard to the adjacent tooth structures within the jaw. Additional
      criteria in the evaluation of jaw lesions are demarcation, morphological
      characteristics, cortical involvement, periosteal and soft tissue changes.

PMID- 16607877
TI  - Cookie bite lesion.

PMID- 16607878
TI  - Dissection of the infrarenal abdominal aorta in blunt trauma.

PMID- 16607879
TI  - Doctoral theses: pre-surgical evaluation of language and memory in patients with
      refractory temporal lobe epilepsy using functional magnetic resonance imaging.

PMID- 16607880
TI  - Evaluation of multislice Ct for the diagnosis of pulmonary embolism.

PMID- 16607881
TI  - [To know is to relieve; "lifestyle-related diseases"; as they are now and how to
      prevent them].
AB  - Hypertension, diabetes mellitus, hyperlipidemia and obesity have recently defined
      as lifestyle-related diseases. A common background of these lifestyle-related
      disease is nutritional excess and its consequence, obesity. Recent advances in
      the biology of adipose tissue have revealed that adipose is not simply an energy
      storage organ but it also secretes a variety of molecules which affect the
      metabolism of the whole body. Dysregulation in the secretion of these adipose
      specific secretory proteins may have important roles in the lifestyle-related
      diseases. It may be a great concern for many people to know about lifestyle
      related diseases and how to manage and prevent them. The purpose of this citizen
      joint symposium is to broaden citizen's knowledge on the mechanism and
      appropriate management of lifestyle-related disease. We hope that this symposium
      provide useful informations to the participants about the current information in
      the management of lifestyle-related diseases.

PMID- 16607882
TI  - Generation of a constitutively active mutant of human GPR48/LGR4, a G-protein
      coupled receptor.
AB  - GPR48, also known as leucine-rich repeat (LRR)-containing G-protein-coupled
      receptor 4 (LGR4), is a member of the G-protein-coupled receptor (GPCR) family of
      proteins. However, its biological functions remain unclear, since neither its
      ligand nor signal transduction pathway have been identified, and it is usually
      difficult to solve the function of such orphan receptors. The aim of this study
      was to generate a constitutively active form of human GPR48, that would form a
      ligand-independent active conformation and may function in a similar manner to
      activated GPR48 following ligand binding. We introduced four independent
      mutations into transmembrane domains V and VI of a human GPR48 cDNA. The wild
      type and mutant GPR48s were expressed in HEK293 cells by transient transfection
      of appropriate expression plasmids. Since ligand-activated receptors for
      gonadotropins, which are structurally similar to GPR48, stimulate adenylate
      cyclase and increase cellular cyclic AMP, we investigated, whether the GPR48
      transfected cells showed altered cyclic AMP levels. The cellular cyclic AMP level
      in HEK293 cells was increased following transfection of wild-type GPR48 in a dose
      dependent manner. Moreover, transfection of a GPR48-T7551 mutant, in which
      threonine-755 was replaced with isoleucine, dramatically increased the cyclic AMP
      level. Stable transformants derived from HCT116 cells that constitutively
      expressed the GPR48-T7551 mutant also showed high cyclic AMP levels. These
      results indicate that the GPR48-T7551 mutant is a constitutively active mutant.
      This mutant may be useful for studying the biological functions of GPR48 and
      GPR48-mediated signal transduction, even if the specific ligand remains unknown
      in the future.

PMID- 16607883
TI  - [Activation markers of lymphocytes as indicators of immune system dysregulation
      in inflammation].
AB  - Three groups of activation antigens (receptors) of human peripheral blood
      lymphocytes (CD23, CD54--functional activation antigens, CD25 and CD71--early
      activation antigens and HLA-DR and CD95--late activation antigens) were studied
      in patients with inflammatory diseases of different types. All kinds of
      inflammation are independent of etiological factors and are associated with
      immune system activation. Inflammation induced by tissue injury or invasion of
      nonspecific microorganisms leads to a rapid rise in the count of lymphocytes
      expressing early markers of activation. Inhibition of inflammation occurs with a
      significant rise in peripheral blood lymphocytes with receptor of activation
      apoptosis CD95 (Fas-antigen). High number of lymphocytes with early markers of
      activation in line with high number of blood CD95+ lymphocytes take place in
      allergic and autoimmune diseases for a long time. Abnormal regulation of
      activation processes in lymphocytes in allergic and autoimmune diseases consists
      in the absence of lymphocyte activation inhibition in spite of high expression of
      CD95.

PMID- 16607884
TI  - [Use of labeled compounds in determination of intensity and direction of
      substances transport from blood to the viscera].

PMID- 16607885
TI  - [Correction of endotoxicosis in alcoholic pancreatitis in elderly and senile
      patients using discrete plasmapheresis].
AB  - The majority of critical conditions in man occur in diseases accompanied with
      development of endogenic intoxication syndrome. The search for universal
      criterion and design of highly effective programs for correction of this
      condition are of great importance for internal medicine and surgical practice.
      Discrete plasmapheresis for endotoxicosis in elderly and gerontological patients
      has its specific features which should be taken into consideration because of low
      adaptation abilities of such group of patients.

PMID- 16607886
TI  - [Modulation of endotoxin-induced respiratory splash of granulocytes and monocytes
      in patients with Familial Mediterranean Fever by iodine-lithium-alpha-dextrin and
      sodium thiosulfate].
AB  - The effect of an endotoxin--E. coli liposaccharide (LPS) of serotype 026:B6--on
      the respiratory splash (RS) of neutrophils and monocytes in peripheral blood of
      patients with Familial Mediterranean Fever (FMF) was studied. It is shown that
      FMF patients have a periodic increase (during an attack) and a decrease (in the
      period of remission) in endotoxin-induced RS of neutrophils and monocytes. LPS
      stimulates chemotoxis-induced RS of neutrophils and monocytes in patients both in
      the period of remission and during the attack equally effectively. Iodine-lithium
      alpha-dextrin and sodium thiosulfate have a marked anti-endotoxic effect which
      manifests with quick neutralization of endotoxin activity on RS of monocytes and
      neutrophils in FMF patients both during the attack and remission.

PMID- 16607888
TI  - [Integral plasma antioxidative capacity and its relationship to the levels of
      trace elements].

PMID- 16607887
TI  - [Red cell membrane phospholipids in patients with chronic bronchitis combined
      with urolithiasis].
AB  - Red cells from patients with chronic non-obstructive bronchitis in clinical
      remission were used for investigation of phospholipid composition of the red cell
      membranes in case of bronchopulmonary pathology combination with urolithiasis.
      Structural changes in the above composition were seen from decreased amount of
      phosphatidyl choline and sphiringomyelin in increased proportion of phosphatidyl
      serine and phosphatidyl ethanolamine. Thus, cell membrane structural state of
      patients with chronic bronchitis combined with urolithiasis showed a shift to an
      increase in phospholipid double layer packing density and common red cell lipids
      saturation.

PMID- 16607889
TI  - [Modification of red cell membranes with perftoran in papaine emphysema in rats].
AB  - Papaine emphysema model on 75 mongrel mature white male rats (10 intact rats were
      control) was used to study the size, form, surface architechtonics, deformability
      and state of membrane-receptor erythrocyte complex before and after perftoran
      intraperitoneal administration. Perftoran emulsion produced a membrane-modulating
      effect with recovery of hormonal reception sensitivity, PHA-, cAMP-receptor
      systems as well as restoration of erythrocytic normocytosis and diskocytosis.

PMID- 16607890
TI  - [Cold-induced changes in blood lipoproteins in normotensive and hypertensive
      rats].
AB  - It is shown that in thermoneutral conditions ISIAH (Inherited Stress-Induced
      Arterial Hypertension) hypertensive rats had a lower level of high-density
      lipoproteins (HDLP) in plasma and a higher atherogenic coefficient compared to
      normotensive Wistar rats. After cooling there were different changes in
      fractional composition of plasma lipoproteins both in normo- and hypertensive
      rats. These changes depended on the cooling rate and were more pronounced after
      slow cooling. Slow cooling resulted in a more significant increase of plasma HDLP
      and in a greater decrease in LDLP and atherogenic coefficient in hypertensive
      rats compared to normotensive ones.

PMID- 16607891
TI  - [Mineral homeostasis in myocardial infarction and correction of its
      abnormalities].

PMID- 16607892
TI  - [The role of oxygen radicals in metabolic disorders in the kidneys of patients
      with acute and chronic pyelonephritis].

PMID- 16607893
TI  - Chronic ischemic mitral regurgitation.
AB  - Ischemia-induced mitral insufficiency (IMI) can occur when a papillary muscle
      ruptures in the acute phase of myocardial infarction (MI) or, more commonly, when
      ischemic heart disease reaches the chronic stage, with or without infarction. In
      the latter case it can be distinguished from organic mitral regurgitation because
      the structure of the valve and the subvalvular apparatus are not affected. Many
      factors contribute to the complex mechanism of IMI: incomplete closure of the
      valve is mainly a result of changes in the geometry of the left ventricle, the
      mitral annulus, papillary muscles and to hemodynamic conditions rather than to
      muscular dysfunction of the papillary muscles. IMI is assessed mainly by Doppler
      echocardiography. The adverse prognostic value of chronic IMI following an
      infarction has recently been described. Regurgitant orifice area (ROA) > 20 mm2
      and a resting regurgitated volume > 30 ml or an increase in ROA > 13 mm2 on the
      treadmill-exercise echocardiogram were identified as relevant predictors of
      death. The therapeutic implications, both surgical and interventional, are
      currently under development using annuloplasty coupled, perhaps, to new
      strategies.

PMID- 16607894
TI  - Aortic valve sclerosis is associated with an echocardiographically determined
      thinner aortic wall.
AB  - BACKGROUND AND AIM OF THE STUDY: The aortic valve leaflets plus the aorta and
      sinuses of Valsalva are a functional unit that optimizes distribution of the
      diastolic pressure load on the aortic valve leaflets. The study aim was to
      examine the hypothesis that echocardiographically measured parameters of aortic
      wall stress at the level of the sinuses of Valsalva, namely aortic wall thickness
      and luminal diameter, are associated with the presence of aortic valve sclerosis
      (AVS). METHODS: Among 103 patients (age range 60-70 years) referred for
      echocardiography at a university hospital, 59 with AVS were compared to an age
      matched control group (n = 44) with no echocardiographic abnormalities. Subjects
      with congenital bicuspid aortic valves were excluded from the study.
      Transthoracic echocardiographically obtained digital loop recordings were
      reviewed and two-dimensionally guided measurements were made at the level of the
      aortic annulus and sinus of Valsalva using electronic calipers, from the
      parasternal long-axis view. RESULTS: There was a significant linear relationship
      and direct correlation between aortic root diameter at the sinus of Valsalva and
      body surface area (BSA) (r = 0.488, F = 31.6, p < 0.001) in both the AVS (r =
      0.491, F = 18.1, p < 0.001) and control (r = 0.571; F = 20.3; p < 0.001) groups.
      After adjusting for BSA, aortic wall thickness was significantly (p < 0.05)
      smaller in AVS patients compared to controls. Luminal diameter was not
      significantly different between the two groups. The specificity of the
      relationship with sinus of Valsalva wall thickness was confirmed by an absence of
      any difference in aortic root thickness at the level of the aortic annulus in AVS
      compared to controls. CONCLUSION: AVS is associated with a thinner aortic wall at
      the level of the sinus of Valsalva. This novel finding suggests that a thinner
      aortic wall, a reflection of its constituents, likely acting through its
      contribution to reduced aortic compliance and increased aortic stress, leads to
      the thickening of aortic valve leaflets characteristic of AVS. Further
      understanding of this relationship may unravel the pathophysiology of this type
      of aortic valve disease.

PMID- 16607895
TI  - Prevalence of atherosclerosis of the coronary and extracranial cerebral arteries
      in patients undergoing aortic valve replacement for calcified stenosis.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate the coexistence
      of various atherosclerotic changes in patients with non-rheumatic calcific aortic
      valve stenosis (AS), since calcific AS shares various clinical risk factors with
      atherosclerosis. METHODS: In 282 consecutive patients with severe calcific
      stenosis of a tricuspid aortic valve scheduled for aortic valve replacement, the
      prevalence of atherosclerotic changes of the coronary and extracranial cerebral
      arteries were assessed using coronary angiography and Doppler sonography,
      respectively. RESULTS: The severities of coronary and extracranial cerebral
      artery atherosclerosis were significantly associated (p = 0.005). The prevalence
      and severity of both coronary and extracranial cerebral artery atherosclerosis
      were age-dependent. Coronary or extracranial cerebral artery stenosis was present
      in 59% and 16% of patients, respectively, while 91% of the study population and
      all patients aged > 80 years showed atherosclerosis of the coronary and/or
      extracranial cerebral arteries. CONCLUSION: The data obtained indicated a very
      high prevalence of atherosclerotic changes in patients with calcific AS,
      suggesting pathogenetic similarities of both disorders. Routine screening of the
      extracranial cerebral arteries is warranted in all patients with calcific AS and
      scheduled for valve replacement.

PMID- 16607896
TI  - Aortic valve repair for aortic regurgitation: intermediate-term results in
      patients with tricuspid morphology.
AB  - BACKGROUND AND AIM OF THE STUDY: Surgical results after aortic valve repair in
      patients with aortic regurgitation (AR) of tricuspid valve morphology and with no
      evidence of aortic root disease have not yet been clarified. METHODS: Between
      January 1994 and June 2001, aortic valve repair was performed in 40 patients
      (eight females, 32 males; mean age 61.0 +/- 10.5 years) of this type. Surgical
      results and follow up data were summarized after aortic valve repair (for AR) in
      these patients. RESULTS: One patient died in hospital (mortality 2.5%). The mean
      cardiopulmonary bypass time was 143.5 +/- 47.4 min, and mean aortic cross-clamp
      time 99.8 +/- 34.3 min. At follow up, the mean AR grade was 1.5 +/- 0.8 and mean
      NYHA class 1.0 +/- 0; both parameters showed significant improvement compared to
      preoperative status (p < 0.0001). Survival was 94.9% at one year and 82.6% at
      five years. The five-year reoperation-free rate was 87%. CONCLUSION: Aortic valve
      repair for AR in patients with tricuspid valve morphology is a safe procedure
      that provides good intermediate-term results.

PMID- 16607897
TI  - Hemolysis, high-intensity transient signals (HITS) and hemodynamic results after
      aortic valve replacement with the Medtronic Hall Easy-Fit heart valve prosthesis.
AB  - BACKGROUND AND AIM OF THE STUDY: Previous studies have shown a correlation
      between type, orientation and valve size of mechanical heart valve prostheses and
      the incidence of high-intensity transient signals (HITS). The study aim was to
      investigate the presence of HITS and hemolysis and the impact of valve size and
      hemodynamic parameters following aortic valve replacement (AVR) using the new
      Medtronic Hall Easy-Fit prosthesis. METHODS: A total of 150 patients (120 males,
      30 females; mean age 62 +/- 8 years; range: 32-78 years) underwent AVR (n = 94;
      63% concomitant procedures) with the Easy-Fit valve in its optimal orientation.
      Patients were investigated at between three and 36 months after AVR using
      transcranial Doppler examination of the right and left middle cerebral artery,
      and the incidence of HITS was determined. For evaluation of hemolysis, serum
      lactate dehydrogenase (LDH), hemoglobin and bilirubin were measured. These
      parameters were related to valve size. Transthoracic echocardiography was
      performed in all patients. RESULTS: Among the patients, 112 (75%) showed no or
      low HITS (34% none, 41% < 30/h), while only 38 (25%) had elevated HITS (range 31
      100/h, 14%; range > 100/h, 11%). Statistical analysis showed a linear association
      between the HITS count and valve size. A positive correlation between valve size
      and LDH was observed; hemoglobin and bilirubin showed normal values. CONCLUSION:
      The valve size-dependent increase in LDH after AVR corresponds with the
      observation that the presence of HITS increases with valve size. In light of
      these findings, the surgical approach to implant the largest size Easy-Fit valve
      possible should be discussed, given the excellent hemodynamic results provided by
      the valve, even in smaller sizes.

PMID- 16607898
TI  - The valve of choice in elderly patients and its influence on quality of life: a
      long-term comparative study.
AB  - BACKGROUND AND AIM OF THE STUDY: Mechanical heart valves are preferred for
      younger patients in order to avoid valve structural deterioration, but
      bioprosthetic valves are favored for older patients to avoid long-term
      anticoagulation. With increasing patient longevity, controversy persists
      regarding the valve of choice in the 65- to 75-year-old population. With
      improving patient survival, long-term quality of life (QOL) is a critical element
      in helping to resolve this controversy. METHODS: A retrospective analysis was
      conducted of 1,104 consecutive patients, aged 65-75 years, who underwent valve
      replacement between July 1976 and December 1999. Valves implanted were either a
      Carpentier-Edwards (CE) porcine bioprosthesis (596 patients) or a St. Jude
      Medical (SJM) mechanical valve (508 patients), with and without concomitant
      coronary artery bypass grafting. QOL was assessed using the Short Form (SF-36)
      Health Survey for both groups at the time of follow up, which was 98.2% complete.
      Comparable patient groups were analyzed within quintiles by propensity score
      analysis. RESULTS: Operative mortality was 9.4% (n = 56) for CE patients, and
      5.3% (n = 27) for SJM patients (p = 0.014). Propensity score analysis revealed no
      significant difference in operative mortality between groups in any of the five
      quintiles. Actuarial survival for hospital survivors favored SJM patients (p =
      0.005). However, when compared within quintiles, there was no significant
      difference between groups. QOL summary scores were significantly higher for
      physical health (p = 0.007) for SJM patients, but similar between valve groups
      for mental health. Comparison within quintiles revealed no significant difference
      between the groups in either area. CONCLUSION: When comparing the outcomes of
      mechanical versus bioprosthetic valve replacement, considerable care must be
      exercised to ensure the clinically relevant similarity of groups. When evaluating
      comparable patient groups, there was no advantage in either survival or QOL for
      patients aged 65-75 years receiving a CE or SJM valve.

PMID- 16607899
TI  - Valve surgery in octogenarians: a safe option with good medium-term results.
AB  - BACKGROUND AND AIM OF THE STUDY: The number of octogenarians is increasing in
      industrialized societies, and many patients aged over 80 years have heart valve
      disease which is amenable to surgical treatment. The perioperative outcomes and
      long-term results in very elderly patients undergoing valve surgery were
      evaluated. METHODS: A retrospective analysis was conducted of 2,791 patients with
      long-term follow up, who underwent valve surgery between 1990 and 2002. Of these
      patients, 132 (68 males, 64 females) were aged over 80 years (mean age 82 +/- 2
      years; range: 80-94 years). RESULTS: Ninety-five patients (71.9%) underwent
      aortic valve replacement, 36 (27.3%) mitral surgery, and one patient had double
      valve surgery. Sixty-five patients (49.2%) required concomitant coronary artery
      bypass grafting. There were 11 (8.3%) redo procedures. Patients aged over 80
      years were significantly more symptomatic preoperatively than their younger
      counterparts (NYHA class III-IV 90.9% versus 69.0%, p < 0.001), with more
      congestive cardiac failure, hypertension, peripheral vascular disease,
      obstructive pulmonary disease, and renal failure (all p < 0.05). Perioperative
      mortality did not, however, differ significantly between groups (< 80 years
      versus > or = 80 years, 2.9% versus 4.6%, p = 0.10). There was also no difference
      in the composite end point of in-hospital death, renal failure, stroke, low
      output state, myocardial infarction, or sternal wound infection (< 80 years
      versus > or = 80 years, 10.5% versus 11.4%, p = 0.8). The mean follow up period
      was 66 +/- 44 months (< 80 years) versus 61 +/- 37 (> or = 80 years). Late
      mortality was higher in the elderly group (10-year survival 37.9% versus 68.2%, p
      < 0.001) and preoperative atrial fibrillation (RR 2.75; CI: 1.44-5.23), coronary
      artery disease (RR 1.98; CI 1.12-3.52) and congestive cardiac failure (RR 2.13;
      CI: 1.10-4.11) were independent predictors of late mortality. The groups did not
      differ with respect to long-term valve-related events, with the exception of
      fewer reoperations among elderly patients. CONCLUSION: Valve surgery in selected
      octogenarians is associated with low morbidity and mortality. The outlook after
      surgery is very good, and surgery should not be denied to this group on the basis
      of age alone.

PMID- 16607900
TI  - Long-term outcome of the MitroFlow pericardial bioprosthesis in the elderly after
      aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: The current trend in Europe and the USA
      demonstrates an increased number of tissue valves being implanted. However,
      studies presenting long-term follow up of the Mitroflow pericardial bioprosthesis
      are relatively scarce. In the present study, the long-term outcome of the
      Mitroflow in the aortic position was analyzed in a geriatric population using
      actuarial statistics; risk factors for early and late mortality were also
      evaluated. METHODS: Between 1990 and 1993, 152 elderly (mean age 79.5 +/- 3.1
      years; range: 75-91 years) patients each received a Mitroflow bioprosthesis
      implanted in the aortic position. A follow up was conducted in January 2003 and
      was 100% complete. Concomitant coronary artery bypass grafting was performed in
      74 patients (49%). Valve-related outcomes were evaluated using actuarial
      statistics. Overall survival was compared to that in an age- and gender-matched
      population. A multivariate analysis of risk factors for mortality was also
      performed. RESULTS: Actuarial freedom from structural valve deterioration was 99%
      and 82% at five and 10 years, respectively. Actuarial freedom from stroke,
      bleeding, prosthetic valve endocarditis and valve explant at 10 years were 80 +/-
      5%, 94 +/- 3%, 93 +/- 3% and 89 +/- 4%, respectively. Risk factors for mortality
      during follow up were male gender, small valves (< or = 21 mm), preoperative NYHA
      class III/IV, greater age, and long intraoperative perfusion time. CONCLUSION:
      The Mitroflow pericardial bioprosthesis demonstrated a good long-term performance
      after aortic valve replacement, suggesting it to be a feasible option in elderly
      patients.

PMID- 16607901
TI  - Cardiac resynchronization therapy as an alternative to valve replacement in high
      risk patients with a chronically decompensated aortic stenosis?

PMID- 16607902
TI  - Cardiac resynchronization therapy as an 'alternative' approach to a non-operable
      severe aortic stenosis with left ventricular dysfunction.
AB  - Severe symptomatic aortic stenosis (AS) is an indication for surgical replacement
      of the aortic valve in adults. Patients are often affected by comorbidities, and
      the surgical indication is sometimes problematic. Non-surgical techniques have
      been developed during the past few years, though their roles have not yet been
      established. Cardiac resynchronization therapy has been shown to be effective in
      selected patients, but no data yet exist on the role of this therapy in AS
      patients. The case is presented of a patient with non-operable severe symptomatic
      AS and cardiac dissynchrony who showed significant improvement following the
      implantation of a biventricular pacemaker.

PMID- 16607903
TI  - Transmural left ventricular shear strain alterations adjacent to and remote from
      infarcted myocardium.
AB  - BACKGROUND AND AIM OF THE STUDY: In some patients, dysfunction in a localized
      infarct region spreads throughout the left ventricle to aggravate mitral
      regurgitation and produce deleterious global left ventricular (LV) remodeling.
      Alterations in transmural strains could be a trigger for this process, as these
      changes can produce apoptosis and extracellular matrix disruption. The hypothesis
      was tested that localized infarction perturbs transmural strain patterns not only
      in adjacent regions but also at remote sites. METHODS: Transmural radiopaque
      beadsets were inserted surgically into the anterior basal and lateral equatorial
      LV walls of 25 sheep; additional markers were used to silhouette the left
      ventricle. One week thereafter, 10 sheep had posterior wall infarction from
      (obtuse marginal occlusion, INFARCT) and 15 had no infarction (SHAM). Four
      dimensional marker dynamics were studied with biplane videofluoroscopy eight
      weeks later. Fractional area shrinkage, LV volumes and transmural
      circumferential, longitudinal and radial systolic strains were analyzed. RESULTS:
      Compared to SHAM, INFARCT greatly increased longitudinal-radial shear (mid-wall:
      0.07 +/- 0.07 versus 0.14 +/- 0.06; subendocardium: 0.03 +/- 0.07 versus 0.20 +/-
      0.08) in the inner half of the lateral LV wall and increased circumferential
      radial shear (mid-wall: 0.03 +/- 0.05 versus 0.10 +/- 0.04; subepicardium: 0.02
      +/- 0.05 versus 0.12 +/- 0.10) increased in the outer half of the LATERAL wall.
      In the ANTERIOR wall, INFARCT also increased longitudinal-radial shear (midwall:
      0.01 +/- 0.05 versus 0.12 +/- 0.04; subendocardium: 0.04 +/- 0.09 versus 0.25 +/-
      0.20) in the inner layers. CONCLUSION: Increased transmural shear strains were
      found not only in an adjacent region, but also at a site remote from a localized
      infarction. This perturbation could trigger remodeling processes that promote the
      progression of ischemic cardiomyopathy. A better understanding of this process is
      important for the future development of surgical therapies to reverse destructive
      LV remodeling.

PMID- 16607904
TI  - A preoperative and intraoperative predictive model of prolonged intensive care
      unit stay for valvular surgery.
AB  - BACKGROUND AND AIM OF THE STUDY: In developing countries, the costs of intensive
      care unit (ICU) stay are very high for patients after valve surgery. In addition,
      patients with a prolonged ICU stay have a poor prognosis compared to those with a
      short ICU stay. The study aim was to develop a specific risk model and to use a
      logistic EuroSCORE model to predict prolonged ICU stay after valve surgery.
      METHODS: A total of 507 consecutive patients undergoing valve surgery were
      studied using univariate and multivariate analyses. Prolonged ICU stay was
      defined as five days or more. Stepwise logistic regression analysis was used to
      identify the risk factors for prolonged ICU stay. These variables were then used
      to calculate a prognostic score (S) and a predicted probability (P) for prolonged
      ICU stay. A receiver operating characteristic (ROC) curve was calculated to
      measure the prognostic value of the new risk model and logistic EuroSCORE model.
      Sensitivity and specificity analysis were used for evaluation. RESULTS:
      Multivariate logistic regression analysis showed that age > or = 65 years, left
      ventricular ejection fraction (LVEF) < or = 50%, cardiothoracic ratio (CTR) > or
      = 0.68, previous cardiac surgery, maximal voluntary ventilation (MVV)
      observed/predicted < 71% and repeat cardiopulmonary bypass (CPB) during surgery
      were risk factors. Mitral valve surgery reduced the risk of prolonged ICU stay.
      Observed probabilities compared well with predicted probabilities. The ROC curve
      produced an area under the curve (AUC) value of 0.81 for prolonged ICU stay.
      Based on predicted probability, patients were classified as low-risk (0 < or = P
      < 10%), intermediate-risk (10% < or = P < 20%), high-risk (20% < or = P < 40%)
      and very high-risk (> or = 40%) groups. A P-value > or = 40% was used as a cut
      off point for the prognostic test. The specificity of this test was 97%,
      sensitivity 32%, positive predictive value 62%, negative predictive value 89%,
      positive likelihood ratio 10.67, and negative likelihood ratio 0.70. The ROC
      curve of a logistic EuroSCORE model gave an AUC value of 0.66 for prolonged ICU
      stay. CONCLUSION: The study results showed that individual patients undergoing
      valve surgery could be stratified according to their risk factors for prolonged
      ICU stay. High-risk patients may require more careful preoperative and
      postoperative management to reduce postoperative mortality, morbidity, the length
      of ICU stay, and therefore the cost of valve surgery.

PMID- 16607905
TI  - Clinical anatomy of the atrioventricular node artery.
AB  - BACKGROUND AND AIM OF THE STUDY: The study aim was to describe the topographical
      relationship of the atrioventricular (AV) node artery and mitral valve annulus
      fibrosus with regard to AV node dysfunction following mitral valve replacement or
      ring annuloplasty. METHODS: The anatomy of the AV node artery was analyzed in 55
      human hearts without previous pathological alterations. Selective coronary
      angiograms were performed to identify the AV node origin. Run-off of the AV node
      artery and its topographical relationship to the mitral valve attachment was
      analyzed in dry-dissected hearts. The position of the AV node was verified by
      histological sectioning. RESULTS: The AV node artery originated from the right
      coronary artery in 73% of examined cases, and from the left coronary artery in
      27% of cases. The left AV node artery was closely related to the mitral valve
      attachment, especially at the area of the left proximal part of the posterior
      leaflet. CONCLUSION: These morphological data were compared to clinical reports
      emphasizing the postoperative incidence of AV block after mitral valve
      implantation and ring annuloplasty. The occurrence of early postoperative AV node
      block ranged from 20% to 37%. By comparing the present data with available
      literature, it can be stated that there is a high risk of intraoperative damage
      to the left AV node artery during manipulation of the mitral valve annulus
      fibrosus.

PMID- 16607906
TI  - Quattro valve trial at mid-term: December 1996 to November 2004.
AB  - BACKGROUND AND AIM OF THE STUDY: The Quattro valve is a stentless pericardial
      mitral bioprosthesis that is treated with a post-tanning aldehyde capping
      designed to reduce calcification. A prospective trial was started in December
      1996; herein are reported the results of the three centers that performed the
      surgery and followed up patients in the majority of cases. Young patients were
      deliberately included in the trial. METHODS: Follow up data from 175 patients
      (mean age 46 years; range: 12-87 years) were collected and analyzed. Among
      patients, 44% were aged < 40 years. Follow up was 91% complete; mean follow up
      was 3.4 years (range: 0-7.5 years); total follow up was 465 patient-years (pt
      yr). Clinical outcome was assessed according to the AATS/STS guidelines, and
      results analyzed according to Kaplan-Meier product limit calculation and by FDA
      Optimal Performance Criteria (OPC). RESULTS: Early mortality was 1.7% (all non
      valve related). At 60 months after surgery, mean overall survival was 84.8 +/-
      3.6%, mean overall freedom from valve-related death was 99.2 +/- 0.9%, and mean
      overall freedom from calcification, pannus and tears was 96.1 +/- 2.2%. FDA OPC
      values (data for mechanical valve, tissue valve, Quattro valve in patients aged <
      40 years and of all ages, respectively; expressed as %/pt-yr) were as follows:
      thromboembolism/stroke 3.0, 2.5, 0, 0.4; thrombosis 0.8, 0.2, 0, 0; major
      hemorrhage 1.5, 0.9, 0, 0.4; major perivalvular leak 0.6, 0.6, 0.4, 0.6; late
      endocarditis 1.2, 1.2, 1.8, 1.3; calcification/pannus 0, 0, 0.8, 0.6. Statistical
      analysis of these data showed there to be no difference between patients aged
      less or more than 40 years. CONCLUSION: Overall mid-term results with the Quattro
      valve were acceptable. The lack of early calcification in young patients shows
      promise. More young patient-years of follow up will be needed to establish a
      secure indication for use in young, rheumatic patients where anticoagulation
      control is deficient.

PMID- 16607907
TI  - Stented bioprosthetic valve hemodynamics: is the supra-annular implant better
      than the intra-annular?
AB  - BACKGROUND AND AIM OF THE STUDY: The use of stented bioprostheses for aortic
      valve replacement (AVR) in elderly patients with a small aortic annulus may
      result in unsatisfactory hemodynamic performance of the prosthesis. To overcome
      this limitation, new bioprostheses have been designed for complete supra-annular
      implantation, but the actual hemodynamic advantage of the supra-annular implant
      over the intra-annular has not been fully investigated. Accordingly, the
      hemodynamic performance of the same stented bioprosthesis (except for sewing ring
      design) implanted in the supra-annular and conventional intra-annular seating was
      compared. METHODS: Twenty-two patients received an intra-annular implant, and 38
      a supra-annular implant. Age (74 +/- 5 versus 76 +/- 5 years, p = 0.54), gender
      (55% versus 50% males, p = 0.79) and body surface area (1.74 +/- 0.2 versus 1.81
      +/- 0.2 m2, p = 0.13) were similar in both subgroups, who underwent
      echocardiography at 8 +/- 2 and 6 +/- 2 months after surgery, respectively (p =
      0.09). RESULTS: The two patient subgroups had similar preoperative left
      ventricular outflow tract diameters (2.06 +/- 0.2 and 2.1 +/- 0.2 cm; p = 0.62),
      average size of implanted prosthesis (21.0 and 21.3 mm; p = 0.44) and mean
      transprosthetic flow rate (246 +/- 70 and 218 +/- 58 ml/s; p = 0.12). Mean (8 +/-
      3 and 19 +/- 8 mmHg, p < 0.0001), and peak (17 +/- 6 and 40 +/- 13 mmHg; p <
      0.0001) transprosthetic gradients were lower, and mean effective orifice area
      (EOA) (1.78 +/- 0.4 and 1.45 +/- 0.5 cm2, p = 0.006) was higher in patients with
      supra-annular implants than in those with intraannular. The incidence of patient
      prosthesis mismatch (EOA index < 0.85 cm2/m2) decreased from 50% to 34% (p <
      0.0001), with no case of severe mismatch using the supra-annular implant. During
      follow up, a left ventricular mass reduction occurred in patients with supra
      annular implants (from 225 +/- 110 to 173 +/- 59 g/m2; p < 0.03), but not in
      patients with intra-annular implants (173 +/- 62 and 186 +/- 64 g/m2; p = 0.87)
      CONCLUSION: The study results showed that, compared to intra-annular
      implantation, supra-annular implantation of bioprosthetic stented valves in the
      aortic position was associated with a significantly better hemodynamic
      performance of the prosthesis and significant regression of left ventricular
      hypertrophy.

PMID- 16607908
TI  - Eight-year results of Freestyle stentless bioprosthesis in the aortic position: a
      single-center study of 500 patients.
AB  - BACKGROUND AND AIM OF THE STUDY: Stentless bioprostheses may be the future valve
      of choice for aortic valve replacement (AVR). The study aim was to investigate
      mid-term clinical outcome after AVR with the Medtronic Freestyle valve. METHODS:
      Between April 1997 and November 2004, a total of 500 patients (241 females, 259
      males) was implanted with a Freestyle bioprosthesis for AVR, without population
      selection, by a single surgical team at the authors' institutions. Mean patient
      age was 74.5 +/- 9.6 years (range: 26-91 years); 34 patients (7%) were aged < 60
      years, 121 (24%) were aged > 80 years, and 205 (41%) were in NYHA classes III or
      IV. The surgical procedure used included a modified subcoronary technique in 482
      cases and complete root replacement in 18, conducted with mini-extracorporeal
      circulation. Concomitant procedures included coronary artery bypass grafting in
      123 patients (25%), mitral valve repair/replacement in five, and maze in two.
      Follow up was 98% complete; the mean follow up was 31.3 months (range: 4-95
      months). RESULTS: The mean cardiopulmonary bypass time was 98 +/- 26 min, and
      total aortic cross-clamp time 77 +/- 19 min. Operative mortality was 5.2% (n =
      26), and no patients aged under 60 years died. At eight years, freedom from
      structural valve deterioration was 100% (0% in the young population), freedom
      from endocarditis 97.2%, freedom from reoperation 97%, and overall survival 83%.
      Most of the late deaths (n = 56) were of non-cardiac origin, and occurred in
      older patients. After one year, the mean aortic echocardiographic gradient was
      11.5 +/- 1.1 mmHg, and was improved compared to that at discharge. No significant
      aortic insufficiency occurred. CONCLUSION: Use of the Freestyle stentless
      bioprosthesis for AVR resulted in excellent short-term survival in the
      octogenarian population, and excellent mid-term results in the younger
      population. In time, experience will indicate whether the Freestyle should be
      considered as the bioprosthesis of choice for patients of all ages.

PMID- 16607909
TI  - Fate of the autograft and homograft following Ross aortic valve replacement:
      reoperative frequency, outcome, and management.
AB  - BACKGROUND AND AIM OF THE STUDY: The optimal hemodynamic performance and
      potential for growth of the pulmonary autograft has led to expanded indications
      for the Ross aortic valve replacement (AVR) procedure in some centers. The
      authors' institutional mid-term experience was reviewed to assess autograft and
      homograft hemodynamics, growth profile of the autograft, and reoperative
      frequency following Ross AVR. METHODS: Between June 1993 and June 2005, 167
      consecutive patients (mean age 24.9 +/- 15.5 years; range: 1 month to 61 years)
      underwent Ross AVR: 48% of patients were aged < 19 years. Additional procedures
      (n = 78) were performed in 55 patients (33%) at the time of the Ross procedure.
      In total, 151 patients had isolated aortic valve disease and 16 pediatric
      patients had more complex, multi-level left ventricular outflow tract
      obstruction. RESULTS: There were two early deaths (1.2%) and one late death
      (0.6%) over a mean follow up of 5.1 +/- 3.0 years (range: 1 month to 11 years).
      Actuarial survival at 10 years was 98%. In pediatric patients with Konno
      procedure (n = 16), the pulmonary autograft mean annulus diameter increased from
      10.2 to 19.9 mm. Twelve patients underwent 12 reoperations without mortality for
      autograft insufficiency or an ascending aortic aneurysm at a median interval of 5
      years (range: 2 to 8 years): aortic annuloplasty and ascending aorta replacement
      (n = 4), composite aortic root replacement (n = 7), and repair of left
      ventricular pseudoaneurysm (n = 1). Freedom from replacement of the pulmonary
      autograft was 96% at 10 years. Five of the 164 surviving patients (3%) developed
      significant obstruction of the pulmonary homograft and required conduit
      replacement at a median of four years. CONCLUSION: The Ross AVR can be performed
      with good mid-term results, including the pediatric age group. The potential for
      development of significant autograft insufficiency and homograft stenosis
      warrants annual follow up through the intermediate and late terms.

PMID- 16607910
TI  - Preoperative cholesterol levels do not predict explant for structural valve
      deterioration in patients undergoing bioprosthetic aortic valve replacement.
AB  - BACKGROUND AND AIM OF THE STUDY: Structural valve deterioration (SVD) is the most
      common cause of bioprosthetic valve failure. Coronary disease risk factors,
      including hypercholesterolemia, might predict SVD. Here, the relationship was
      examined between preoperative cholesterol levels and SVD in patients undergoing
      bioprosthetic aortic valve replacement (AVR). METHODS: A total of 7,150 patients
      (mean age 68 +/- 12 years) was identified who underwent bioprosthetic AVR at the
      Cleveland Clinic Foundation, between January 1975 and December 2002. Preoperative
      and postoperative variables were retrieved from a prospective, computerized
      database. A parametric method was used to estimate the distribution of valve
      explants; a multivariable risk factor model was then developed to include patient
      demographics, cardiac and non-cardiac comorbidities, valve type and interactions.
      The primary end-point was explant for SVD. All explants were examined, and
      observations were censored at the time of any explant or death. Bootstrap
      analysis was used to validate the model. RESULTS: Among 7,150 patients, 208 had
      explants for SVD. Mean preoperative total cholesterol (TC) was 203 +/- 48 mg/dl,
      HDL-cholesterol 45 +/- 15 mg/dl, and LDL-cholesterol 121 +/- 41 mg/dl. The
      average follow up was 3.7 years, and 1,169 patients (16%) were followed for more
      than eight years. In multivariable analysis, only younger age (p < 0.0001),
      greater body weight (p < 0.0001), elevated serum creatinine level (p = 0.0004)
      and use of a pericardial valve (p = 0.04) predicted SVD. Neither preoperative
      cholesterol nor its fractions predicted valve explant for SVD (log-rank p = 0.19)
      Moreover, no cardiovascular risk factors were predictive of SVD. CONCLUSION:
      Preoperative cholesterol levels do not predict SVD in patients undergoing
      bioprosthetic AVR. Whether long-term hypercholesterolemia or statin therapy
      impacts SVD requires further investigation.

PMID- 16607911
TI  - Reduction of calcification of carbodiimide-processed heart valve tissue by prior
      blocking of amine groups with monoaldehydes.
AB  - BACKGROUND AND AIM OF THE STUDY: Failure of implanted bioprostheses due to
      calcification is a commonly occurring phenomenon. In order to prevent
      calcification, many alternative cross-linking methods to glutaraldehyde (GA) have
      been developed and evaluated. METHODS: In a novel approach an improved
      carbodiimide (EDC) cross-linking method that comprises a two-step process was
      developed. First, the available amine groups in (tissue) collagen were blocked
      with a monoaldehyde, followed by an EDC-activated cross-linking reaction of the
      carboxyl groups in the tissue with a poly (propylene glycol) bis 2-(amino-propyl)
      ether (Jeffamine). RESULTS: Samples processed via this method have shown a
      significantly reduced calcification in a subdermal juvenile rat model compared to
      samples with standard GA treatment. In the present study, heart valve tissue was
      blocked with various monoaldehydes, followed by reaction with Jeffamine using
      carbodiimide cross-linking chemistry. Leaflet calcification was almost eliminated
      using different aldehydes, whereas wall calcification was maximally 95% reduced
      when propionaldehyde was used as blocking agent, as compared to a carbodiimide
      cross-linked control without Jeffamine and blocked amine groups. CONCLUSION:
      Amine blocking and cross-linking technology appears promising in the design of
      the next generation of tissue valves. Calcification was significantly reduced
      compared to GA cross-linking. The mechanistic insight of decreased wall
      calcification is still unknown, and research investigations are ongoing.

PMID- 16607912
TI  - Decellularization does not eliminate thrombogenicity and inflammatory stimulation
      in tissue-engineered porcine heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: In tissue engineering of heart valves using
      decellularized xenogenic valves, it has been suggested that cell elimination
      would result in a biologically inert matrix. The aim of this in-vitro
      investigation was to evaluate different decellularization methods in regard to
      the completeness of cell removal, inflammatory response, and thrombocyte
      activation. METHODS: Decellularized porcine Synergraft valves were compared with
      porcine pulmonary conduits decellularized with Triton X-100, sodium deoxycholate,
      Igepal CA-630 and ribonuclease. Completeness of decellularization was evaluated
      with staining for nuclei and alpha-Gal epitope. Decellularized heart valves with
      and without seeding with endothelial cells (ECs) were incubated with human
      platelet-rich plasma and stained for CD41 and PAC-1 to evaluate thrombocyte
      activation. Samples were processed for laser scanning microscopy (LSM) and
      scanning electron microscopy (SEM). Migration of human monocytic cells towards
      extracted valve proteins was tested. RESULTS: In contrast to the Synergraft,
      complete cell removal and elimination of the alpha-gal epitope was achieved with
      the new decellularization method. Numerous adherent and activated platelets were
      found on the decellularized matrix. This was inhibited by seeding with ECs. Even
      in completely cell-free valve tissue extracellular matrix proteins attracted
      human monocytic cells as in early inflammation, depending on whether porcine or
      human tissue was used. CONCLUSION: Important differences were found in the
      decellularization efficacy of treatment methods. However, even complete
      elimination of cells and their remnants did not result in a biologically inert
      matrix. The decellularized porcine heart valve matrix has the potential to
      attract inflammatory cells and to induce platelet activation. These findings
      suggest that it will be important to control the different inflammation
      stimulating factors if porcine tissues are to be used successfully in tissue
      engineering.

PMID- 16607913
TI  - Flow-dependent re-endothelialization of tissue-engineered heart valves.
AB  - BACKGROUND AND AIM OF THE STUDY: The generation of a functional, non-immunogenic,
      non-thrombogenic construct based on autologous cells seeded onto an acellular
      extracellular matrix is the major goal in heart valve tissue engineering. The
      study aim was to identify culturing conditions required to achieve a stable
      endothelial cell (EC) layer under physiological flow conditions, a prerequisite
      for the requested characteristics. METHODS: Eleven detergent-decellularized ovine
      pulmonary valves (PVs) were statically reseeded in special bioreactors with ovine
      venous ECs (1.2x10(7) cells per valve). The dynamic culture was started with 0.1
      l/min in eight bioreactors. In four bioreactors the initial flow rate was slow,
      and increased by 0.1 l/min twice each day until maximal flow was 0.5 l/min and
      pulsation rate (PR) was 20 beats/min; in four other bioreactors the flow was
      increased by 0.7 l/min/day and reached 2.0 l/min with a PR of 50 beats/min. The
      mean system pressure was maintained at 25 +/- 5 mmHg during the whole dynamic
      cultivation in both groups. Three statically reseeded valves served as baseline.
      After achieving maximal appointed flow, the valves were investigated
      morphologically (hematoxylin and eosin staining, electron microscopy, von
      Willebrand factor, endothelial nitric oxide synthase immunostaining) and for
      metabolic activity (MTS assay). RESULTS: After reseeding, the endothelium
      appeared on the luminal surface of the PV as a non-confluent monolayer. Moderate
      pulsatile circulation induced complete confluence of EC monolayers on both cusp
      sides and the pulmonary wall. A high flow rate led to a partial loss of cells on
      the wall surface with large defects, and to complete cell wash-off from cusps.
      Cusp and wall metabolic activity was significantly higher after culture under
      moderate flow (p < 0.001) than in other groups, and was absent from cusps in high
      flow bioreactors. CONCLUSION: Moderate pulsatile flow with small increments
      stimulates EC proliferation on the ovine decellularized valve scaffold. A rapid
      increase in bioreactor flow to physiological levels leads to significant damage
      of the reseeded endothelium and complete loss of cusp cellularity. This effect
      may be responsible for the in-vivo failure of static reseeded tissue-engineered
      valves exposed to physiological hemodynamic forces.

PMID- 16607914
TI  - Cyclic aortic pressure affects the biological properties of porcine pulmonary
      valve leaflets.
AB  - BACKGROUND AND AIM OF THE STUDY: Native pulmonary valve leaflets (PVL) are
      exposed to lower pressures compared to aortic valve leaflets. Knowledge of the
      biology of PVL exposed to aortic pressures is limited. Hence, the study's aim was
      to investigate the biological properties of PVL subjected to normal aortic
      pressures. METHODS: Porcine PVL were exposed to mean pulsatile pressures of 30
      mmHg or 100 mmHg for 48 h in vitro. Subsequently, PVL were subjected to a mean
      pulsatile pressure of 30 mmHg for 48 h, followed by increased pressure (100 mmHg)
      for additional 48 h. Leaflets were evaluated by measuring collagen, DNA and sGAG
      contents in pressure-exposed and control PVL. Cusp morphology and cell phenotype
      were examined using hematoxylin and eosin staining (H and E) and alpha-smooth
      muscle actin (alpha-SMA) immunohistochemistry, respectively. RESULTS: PVL exposed
      to 30 mmHg showed no significant difference (p > 0.05) in collagen, DNA or sGAG
      contents compared to statically incubated PVL. However, PVL exposed to 100 mmHg
      showed a significant increase (p < 0.05) in both collagen and sGAG contents.
      Collagen content was also significantly increased (p < 0.05) in PVL exposed to
      varying pressures for 96 h compared to PVL exposed to 30 mmHg. The morphology of
      PVL exposed to cyclic pressures was comparable to that of both fresh and static
      leaflets, while alpha-SMA expression was decreased in PVL exposed to cyclic
      pressures when compared to fresh PVL. CONCLUSION: PVL have the ability to
      withstand elevated mechanical conditions by increasing the total collagen and
      sGAG content of the leaflets. The structural integrity of the PVL is unaltered by
      changes in extracellular matrix composition. However, pulsatile pressures on the
      PVL did not preserve the native cell phenotype.

PMID- 16607915
TI  - In response to: Bodnar E, Blackstone EH. Editorial: An 'actual' problem: another
      issue of apples and oranges. J Heart Valve Dis 2005; 14:706-708.

PMID- 16607916
TI  - In response to: Bodnar E, Blackstone EH. Editorial: An 'actual' problem: another
      issue of apples and oranges. J Heart Valve Dis 2005; 14:706-708.

PMID- 16607917
TI  - Morbidity and mortality associated with vasopressin analogue treatment.
AB  - DDAVP is a drug that should be used with caution for each patient individually.
      Particular care is needed to avoid fluid overload and rapid fluctuations in
      sodium concentration. Not only families but physicians as well should be educated
      and aware of the adverse effects of DDAVP, especially in high risk patients.
      Extreme caution is needed in children with severe neurological and developmental
      problems who cannot control their fluid intake themselves. Similarly, caution is
      needed in patients with hypodipsia and DI who have difficulty in balancing water
      intake and DDAVP dose. The treatment of DI is water; however, DDAVP is given to
      avoid a large fluid intake which can result in medullary washout. Frequent home
      monitoring of body weight and regular determinations of serum sodium may help to
      disclose the early phase of over-hydration or dehydration. DDAVP therapy should
      be temporarily interrupted during acute illness, febrile episodes, hot days and
      other conditions with increased water intake. It should be used with considerable
      caution in patients with cystic fibrosis, or renal or cardiovascular diseases. In
      patients with enuresis, it is recommended that DDAVP medication should not be
      continued for longer than 3 months without stopping for 1 week for full
      reassessment. Fluid intake should be limited 1 hour before and 8 hours after the
      dose. Generally, undertreatment with vasopressin analogue is safer than
      overtreatment. A simple measure to avoid overtreatment is to miss one dose once a
      week; a rapid onset diuresis ('washout' effect) provides considerable
      reassurance.

PMID- 16607918
TI  - Vitamin D deficiency and rickets.

PMID- 16607919
TI  - Vitamin D deficiency in the San Francisco Bay Area.

PMID- 16607920
TI  - Nutritional rickets in Las Vegas, Nevada.

PMID- 16607921
TI  - Accuracy of pubertal Tanner staging self-reporting.
AB  - OBJECTIVES: Previous studies examining the reliability of self-reported Tanner
      stages have given conflicting results. We report on the reliability of self
      reported Tanner stages in lean healthy children. METHODS: Self-reported Tanner
      staging of 240 children (130 girls, 110 boys) were compared to the ratings of a
      pediatric endocrinologist who was unaware of the children's self-assessments. The
      correlation between the two approaches was analyzed using kappa statistics.
      RESULTS: 40% (kappa coeffcient = 0.49, p <0.001) and 23% (kappa coefficient =
      0.68, p <0.001) of the girls rated their breast and pubic Tanner stage
      incorrectly, respectively; 39% of the boys (kappa coefficient = 0.49, p <0.001)
      rated their pubic stage incorrectly. The age of the children who self-rated
      correctly and incorrectly was not different; no independent predictors for
      correct Tanner staging self-assessment were found. CONCLUSIONS: The results of
      this analysis suggest that self-rated Tanner pubertal staging is not influenced
      by age and is not a reliable method of assessing Tanner stage.

PMID- 16607922
TI  - Transdermal estradiol priming during clonidine stimulation test in non-growth
      hormone deficient children with short stature: a pilot study.
AB  - The diagnosis of growth hormone (GH) deficiency is strongly influenced by age,
      body mass index and presence of gonadal steroids. Priming with oral estradiol
      (E2) is one possible way to overcome the impact of variable levels of sex
      steroids. We describe the effects of transdermal estradiol (E2-t) priming on GH
      response after clonidine stimulation in prepubertal children with familial short
      stature (group 1, n = 12) or constitutional growth delay (group 2, n = 22). All
      patients underwent a clonidine test (0.1 mg/m2, p.o.) followed by a clonidine
      plus E2-t test (50 microg/day) with a 7-day interval. Before E2-t, basal GH and
      insulin-like growth factor-I (IGF-I) values were similar in the two groups. After
      E2-t priming, basal GH was significantly higher only in group 2. When compared
      with group 1, patients from group 2 had a significant increase of GH peak
      response when submitted to E2-t. The number of patients in both groups with
      adequate GH peak response was higher after E2-t priming. We conclude that E2-t
      priming is able to increase GH peak response after clonidine stimulation and also
      improves the accuracy of the clonidine test in the diagnosis of GH deficiency.
      Compared to oral administration, E2-t delivery can prevent liver toxicity,
      providing a more physiological mechanism of GH secretion.

PMID- 16607923
TI  - Effects of growth hormone (GH) and insulin-like growth factor-I therapy in
      patients with gene defects in the GH axis.
AB  - We report on four patients (3 F) who were diagnosed as having either a 6.7 kb GH1
      gene deletion, a GH1 signalling peptide mutation, or a GH receptor mutation, with
      particular regard to treatment modalities (GH, rhIGF-I) and final height.
      Patients with GH1 gene defects developed anti-GH antibodies (GH-Ab) following GH
      treatment. Surprisingly, growth response to GH was unrestricted in one girl, who
      reached a final height within her target height range, whereas her cousin with
      the identical genetic defect responded far less favourably. Variability in the
      growth inhibiting potency of GH-Ab may therefore depend on genetic disposition,
      specific epitopes, or induction of immunological tolerance. Growth response
      during rhIGF-I treatment carried out in three of the patients was moderate, but
      pubertal development and bone age acceleration occurred in the two patients
      treated at pubertal age. GH resistance, either caused by GH-Ab or GH receptor
      mutations, is still difficult to treat and results in a heterogeneous outcome.

PMID- 16607924
TI  - Growth hormone normalizes pubertal onset in children with cystic fibrosis.
AB  - Children with cystic fibrosis (CF) have a high incidence of delayed puberty and
      poor growth. We retrospectively reviewed pubertal maturation data from 105
      children with CF who had participated in studies on growth hormone (GH). As part
      of the GH study, participants were randomized into two cohorts, one of which was
      treated with GH for 1 year, and then followed off GH, and the other group was
      first followed off GH, and then treated with GH for 1 year. Pubertal staging was
      obtained throughout these studies and we have retrospectively analyzed the data.
      RESULTS: In prepubertal females, GH treatment resulted in a normalized onset of
      breast development as compared to delayed onset in non-treated females. Females
      treated during puberty had a normal tempo of breast development. In prepubertal
      males, GH treatment resulted in a normalized onset of testicular volume compared
      to non-treated males. Testicular size progression was not accelerated in pubertal
      boys treated with GH. CONCLUSION: GH treatment normalizes pubertal onset in
      prepubertal children with CF.

PMID- 16607925
TI  - Experience with long-term glucocorticoid treatment in congenital adrenal
      hyperplasia: growth pattern compared with genetic height potential.
AB  - OBJECTIVE: Long-term replacement treatment with high doses of steroids in
      congenital adrenal hyperplasia (CAH) is known to have a negative influence on
      growth. We evaluated the effects of long-term steroid treatment in patients with
      classical CAH on height development in relation to genetic height potential.
      PATIENTS AND METHODS: Twenty-three patients with CAH (16 females, 7 males, mean
      age: 9.8 +/- 3.5 years) were included in this longitudinal study. The effect of
      steroid treatment on growth was determined by monitoring patients for 8.61 +/-
      3.46 years (2-17 years) while they were treated with hydrocortisone at a mean
      dosage of 17.64 +/- 3.60 mg/m2/day. The height standard deviation scores (Ht
      SDS), target Ht-SDS, and corrected Ht-SDS for target height was calculated for
      all patients. Predicted adult height according to bone age was calculated and it
      was determined whether height was developing according to the genetic height
      potential. In addition, patients were grouped as 'tight control' or 'poor
      control' according to their mean serum 17OH-progesterone or ACTH levels while on
      treatment. We evaluated whether height development was different for the tight
      and poor control groups. RESULTS: The mean chronological age of our patients at
      the time of the study was 9.89 +/- 3.53 years, Ht-SDS -0.77 +/- 1.57, target
      height (TH) 161.03 +/- 6.54 cm, TH-SDS -0.60 +/- 0.90, predicted height (PH)
      157.2 +/- 11.16 cm, PH-SDS -1.1 +/- 1.69, and corrected Ht-SDS -0.75 +/- 1.14.
      There was no significant difference between the actual Ht-SDS and TH-SDS of our
      patients (p >0.05) but the corrected Ht-SDS was less than zero. Only 28.5% of our
      patients had normal height according to their genetic potential while 71.5% were
      shorter than their genetic height potential. While the Ht-SDS and corrected Ht
      SDS were similar in the tight and poor metabolic control groups, the predicted
      height was significantly greater in the tight control group. CONCLUSION: We
      demonstrated that a hydrocortisone dose of 17.64 +/- 3.60 mg/m2/day in classical
      CAH had a negative influence on height development for genetic height potential
      in 8.5 years of follow-up and that it is necessary to use the lowest possible
      steroid dosage by individualizing the dose.

PMID- 16607926
TI  - The role of cord blood IGF-I levels in preterm osteopenia.
AB  - OBJECTIVE: Osteopenia is a frequent condition in preterm infants. This
      prospective study was designed to assess the relationship between cord blood
      insulin-like growth factor-I (IGF-I) levels and bone mineralization in healthy
      premature infants. METHODS: Twenty preterm infants (ten males and ten females)
      were studied. We determined the bone mineral density (BMD) and bone mineral
      content (BMC) of healthy premature infants by dual-energy X-ray absorptiometry
      and also studied the correlation between IGF-I and other parameters and the
      influence of cord blood IGF-I concentrations on bone mineralization in these
      infants. RESULTS: The mean concentration of IGF-I was 13.6 +/- 16.9 ng/ml and BMD
      and BMC were 0.249 +/- 0.06 g/cm2 and 3.09 +/- 1.18 g, respectively. Cord serum
      levels of IGF-I had significantly positive correlations with BMD (r = 0.605, p =
      0.008), but not BMC (r = 0.242, p = 0.367). In stepwise regression analysis, IGF
      I emerged as a significant predictor of BMD (beta = 0.595, p = 0.015)
      contributing to 35.4% of its variability. CONCLUSION: We found a relationship
      between cord blood IGF-I and BMD in preterm neonates, suggesting that even within
      an unremarkable population, IGF-I might be important to ensuring bone health.

PMID- 16607927
TI  - Relationship between different fasting-based insulin sensitivity indices in obese
      children and adolescents.
AB  - OBJECTIVES: To evaluate insulin sensitivity from data obtained from baseline
      values and from an oral glucose tolerance test (OGTT) in normal and obese
      children and adolescents. STUDY DESIGN: We recruited 89 children 4-10 years old
      and 82 adolescents 11-18 years old divided into moderately obese (Mod OB),
      severely obese (Severe OB), and non-obese (Non-OB) controls. We evaluated the
      relationship between four simple measures of insulin sensitivity: homeostatic
      model assessment (HOMA-IR), quantitative insulin sensitivity check index
      (QUICKI), fasting glucose to insulin ratio (FGIR), and fasting insulin resistance
      index (FIRI), with an insulin sensitivity measure derived from the standard 2
      hour OGTT, the composite whole body insulin sensitivity index (ISI Comp).
      RESULTS: The strongest correlation was between QUICKI and ISI Comp and between
      FGIR and ISI Comp, (correlations [r] 0.81-0.85 in the Mod OB and 0.63-0.67 in the
      Severe OB). The relationship between HOMA-IR and ISI Comp and between FIRI and
      ISI Comp did not appear to be as strong (correlations [r] -0.36 and -0.53 in Mod
      OB and Severe OB, respectively). Moderately obese and severely obese children had
      fasting and 2-hour insulin levels 2-3 fold higher than the control group.
      CONCLUSIONS: QUICKI and FGIR, are strongly correlated with OGTT measures of
      insulin sensitivity in children and adolescents with different degrees of
      obesity. These simple fasting-based indices may help the pediatrician identify
      patients at risk of developing insulin resistance.

PMID- 16607928
TI  - Serum superoxide dismutase activity and nitric oxide do not correlate with
      arterial stiffness in children with type 1 diabetes mellitus.

PMID- 16607929
TI  - Ovarian insufficiency in congenital lipoid adrenal hyperplasia begins in infancy.
AB  - The aim of the present study was to investigate ovarian function in a 46,XX
      female patient with congenital lipoid adrenal hyperplasia (lipoid CAH) during
      infancy and childhood. We measured serum gonadotropin and estradiol levels
      regularly from 6 months to 10.9 years of age. Serum FSH levels were clearly
      elevated during the first 2 years of life; they decreased gradually until the age
      of 5 years and they then fell into the normal range for a prepubertal female.
      Serum LH levels were elevated until the age of 2 years and they then fell into
      the normal range. Serum estradiol levels were always in the normal prepubertal
      range. Pelvic ultrasonography performed at the age of 9 months and at 9.8 years
      of age showed normal uterine and ovarian morphology for a prepubertal female. In
      conclusion, our data suggest that ovarian insufficiency in lipoid CAH begins in
      infancy.

PMID- 16607930
TI  - Effects of 3 years of intravenous pamidronate treatment on bone markers and bone
      mineral density in a patient with osteoporosis-pseudoglioma syndrome (OPPG).
AB  - We present a 21 year-old woman with osteoporosis-pseudoglioma syndrome (OPPG)
      suffering from bone pain and frequent long bone fractures (approximately 1 or 2
      fractures/year) who was treated with i.v. pamidronate for 3 years. OPPG is a rare
      autosomal recessive disorder characterized by severe widespread osteoporosis
      leading to pathological fractures and congenital or early onset blindness. Bone
      mineral density (BMD) (g/cm2) was determined at lumbar spine and femur neck by
      dual energy X-ray absorptiometry. BMD studies were also performed in her parents
      and 18 year-old brother who were phenotypically normal. Within 2 months of the
      first pamidronate treatment the patient reported considerable decrease in bone
      pain and improved mobility. During the treatment period no important side effects
      and no recurrent bone fracture were reported. There were substantial increases in
      BMD, T score and z-score at both lumbar spine and femoral neck during therapy.
      Baseline lumbar spine BMD increased from 0.416 to 0.489 g/cm2 and femoral neck
      BMD increased from 0.455 to 0.532 g/cm2 after 3 years. Although her parents and
      brother did not have any history of fracture, BMD measurements revealed that her
      parents were osteopenic and her brother was osteoporotic. We demonstrated that
      pamidronate therapy seems to be safe and beneficial in both spinal and peripheral
      skeleton osteoporosis in patients with OPPG. Moreover, the present study clearly
      indicates that bone density studies and LRPS gene screening for mutations should
      be performed in phenotypically normal family members of patients with OPPG.

PMID- 16607931
TI  - Poor adherence to the prophylactic use of vitamin D3 in Switzerland.

PMID- 16607932
TI  - Hypomelanosis of Ito and precocious adrenarche in a girl.

PMID- 16607933
TI  - [Clinical evaluation of a quality criteria system for ceramic inlay
      restorations].
AB  - The aim of this study was to test the utilization of a generally accepted quality
      criteria system (United States Public Health Services Modified Quality Criteria)
      in the authors' practice, in the cases of all ceramic inlays and onlays. 41
      ceramic inlays/onlays--29 pressed and 12 laminated--were made for 28 patients.
      Restorations were controlled after 2 years of cementation. According to the USPHS
      criteria system the following characteristics were controlled: anatomic contour,
      marginal integrity, marginal discoloration, color match, secondary caries, and
      surface roughness. In addition, postoperative sensitivity, patient's satisfaction
      and tooth vitality were examined as well. The USPHS quality criteria system
      together with the complementary data proved to be an objective examination method
      that was easily applicable to our clinical practice. On the basis of these
      studies the utilization of this system together with patient's satisfaction,
      tooth vitality and sensitivity records appeared a good basis for a regular
      quality control system of ceramic inlays and onlays.

PMID- 16607934
TI  - [Frequency of oral candidiasis in stem cell transplant patients].
AB  - This study included 80 persons with haematological malignancies receiving stem
      cell transplantation (SCT) who were followed up for a period of 24 months.
      Authors focused on the patients' oral health state and on the correlation between
      the fungal colonisation of the oral cavity and the unstimulated whole saliva flow
      rate, before and after the stem cell transplantation. Carious teeth could be
      detected in 20 out of the 80 persons, although all of them were examined and
      treated by their dentists before taking part in the SCT program. Fungal
      colonization could be shown in 16 patients before the conditioning phase and in
      19 subjects during the aplasia phase of SCT. Hyposalivation (unstimulated whole
      saliva flow rate < or = 0.1 mI/min) was detected in 28 patients. In conclusion
      there was a higher incidence of Candida albicans and other fungal colonization in
      SCT patients suffering from hyposalivation than in those of normal saliva flow
      rate.

PMID- 16607935
TI  - [Relaxation techniques in dentistry].
AB  - In the field of dentistry the increasing number of psychosomatic patients justify
      the introduction of psychological treatment methods into the dental care system.
      In this review authors try to collect the main points of the theoretical
      background and clinical principles of relaxation techniques. Some aspects of the
      concept of mental hygiene is also discussed to help dental professionals working
      in the field of general and psychosomatic dentistry in the orientation in this
      interesting and important field.

PMID- 16607936
TI  - [Quantitative and qualitative comparison of the maxillary bone regeneration after
      beta-tricalcium phosphate and autogenous bone implantation].
AB  - Graft insertion can effectively enhance the regeneration of debilitated bone. The
      effects of an alloplastic bone-replacing material, beta-tricalcium phosphate
      (Cerasorb), and of autogenous bone graft were compared. In 17 edentulous
      patients, the maxillary sinus floor was extremely atrophied to such an extent
      that implant placement was impossible. The Schneiderian membrane was surgically
      elevated bilaterally by insertion of Cerasorb (experimental side) and autogenous
      bone graft (control side). After surgery, the recovery was followed clinically
      and radiologically. After 6 months, 68 bone cylinders were excised from the
      grafted areas and implants were inserted into their places. The bone samples were
      embedded into resin, and the osteointegration of the grafts was studied
      histologically. Trabecular bone volume (TBV) and trabecular bone pattern factor
      (TBPf) were quantified by histomorphometry. Cerasorb proved to be an effective
      bone-replacing material with osteoconductivity; it was capable of gradual
      disintegration, thereby providing space for the regenerating bone. The new bone
      density was not significantly different on the experimental and control sides
      (32.4 +/- 10.9% and 34.7 +/- 11.9%, respectively). However, the graft
      biodegradation was significantly slower on the experimental side than on the
      control side. The TBPf value was lower on the control side than on the
      experimental side (-0.53 +/- 1.7 mm(-1) and -0.11 +/- 1.4 mm(-1), respectively);
      but this difference was not significant. Six months after insertion of the
      grafts, the bone of the augmented sinus floor was strong and suitable for
      anchorage of dental implants, irrespective of whether autogenous bone or Cerasorb
      particles had been applied.

PMID- 16607937
TI  - [Clinical evaluation of digital imaging].
AB  - The rapid progression of digital radiography makes us consider its role in
      different fields of dentistry. The aim of the present survey was to evaluate the
      advantages of digital imaging over the use of radiographic films in the diagnosis
      and therapy of common oral pathologic conditions. The underlying hypothesis was
      that RadioVisiograph (RVG, Trophy Radiology, Marne-la-Vallee, France)--provided
      that there is access to this digital network--is easily available. Thus it can
      provide options for specialists of different dental fields to obtain more
      detailed information in order to make better decisions. Immediately after the
      installation of the new system and then, ten months later we analysed the results
      of digital images and radiographic films in outpatients of different sections at
      our clinic. The quality of both diagnostic procedures was evaluated using a
      questionnaire. Digital imaging was used mainly by specialists of endodontics,
      followed by restorative and prosthetic dentistry in setting up the diagnosis. The
      application of this new technique in parodontology and paediatric dentistry was
      negligible. However, it is worth mentioning that the majority of dentists
      participating in the survey thought that conventional radiographic films gave
      more detailed imaging than the digital technology. To sum it up, currently,
      digital imaging systems may represent an efficient device in diagnostic and
      therapeutic procedures. Nevertheless owing to the technical sensitivity of the
      above systems, traditional radiographic techniques should also be used as an
      option due to their advantages.

PMID- 16607938
TI  - [CE-marking in the dental profession].
AB  - In the present article the authors summarise the meaning and mechanism of CE
      marking in the EU in general and its significance in the dental profession. Their
      goal was to increase the awareness of Hungarian dental professionals to issues of
      quality management in the European Union.

PMID- 16607939
TI  - [Expression in Pichia pastoris and properties of human serum albumin-interferon
      alpha2b chimera].
AB  - To reduce the serum clearance of interferon alpha2b, a chimeric gene encoding an
      human serum albumin(HSA)--human interferon alpha2b(IFNalpha2b) fusion protein was
      overexpressed in Pichia pastoris. After fermentation in a 5L bioreactor, the
      fusion protein, capable of cross-reacting with anti-IFN alpha and anti-HSA
      antibody, was purified from the culture of the recombinant yeast by
      ultrafiltration, blue Sepharose affinity, phenyl hydrophobic interaction and Q
      ion exchange chromatography. Its IFNa2b moiety exhibits antiviral activity
      similar to that of recombinant human IFNa2b. In Cynomolgus monkeys model, The
      fusion protein was detectable in plasma, even 336h after a single does of 90
      microg/kg injection intravenously or subcutaneously. The elimination phase half
      life of the fusion protein was 101h after intravenous injection and 68.2h after
      subcutaneous injection. Its Subcutaneous bioavailability was 67.9%. The enhanced
      pharmacokinetics of interferon a2b fused to human serum albumin suggest its
      promissing application in clinic medicine.

PMID- 16607940
TI  - [Use of Ssp dnaB mini-intein as a fusion partner for preparation of recombinant
      human brain natriuretic peptide].
AB  - Human brain natriuretic peptide (hBNP) was used clinically for the treatment of
      acute decompensated congestive heart failure. In this paper, hBNP was expressed
      as a fusion protein with a histidine tag and Ssp dnaB mini-intein which was
      capable of self-cleavage. After affinity chromatography with Ni-Sepharose and
      renaturation, the fusion protein was enriched with CM-cellulose. Ssp dnaB mini
      intein mediated peptide-bond hydrolysis was triggered by shifting the pH and
      temperature in the CM-cellulose column, which let to the release of hBNP from the
      fusion protein and the separation of hBNP from His-DnaB. The hBNP sample was
      further purified by C4 reverse phase HPLC, and 2.8mg of the peptide with
      homogeneity of 97% was obtained from one liter of culture medium. The biological
      activity was assayed in vitro, which indicated that hBNP had a potent
      vasodilatory effect on rabbit aortic strips with an EC50 of 1.94 x 10(-6) mg/mL.

PMID- 16607941
TI  - [High-level expression of phenylalanine ammonia-lyase in Lactococcus Lactis via
      synthesized sequence based on bias codons].
AB  - To construct a safer and more efficient gene engineering Lactococcus Lactis for
      expressing phenylalaine ammonia lyase (PAL) which will be benefit for PKU
      therapy, pal cDNA of Parsly and synthesized sequence based on Lactococcus Lactis
      bias codons were recombined into two Lactococcus Lactis NICE systems. The
      activities of the expressed PAL were detected, and the effect of Lactococcus
      Lactis bias codons on the expression of exterior protein was analyzed. The
      results showed that the expression level of PAL was increased by using
      Lactococcus Lactis bias codons in both Lactococcus Lactis NICE systems. Through
      which several safer andmore efficient strains of the gene engineering Lactococcus
      Lactis were obtained.

PMID- 16607942
TI  - [Dual promoters enhance heterologous enzyme production from bacterial phage based
      recombinant Bacillus subtilis].
AB  - The effect of dual promoters on recombinant protein production from bacterial
      phage based Bacillus subtilis expression system was investigated. Alpha amylase
      (from Bacillus amyloliquefaciens) and penicillin acylase (from Bacillus
      megaterium) were selected as the indicating enzymes. Both the promoterless genes
      and the promoter-bearing genes were isolated through PCR amplification with
      properly designed primers, and were inserted into plasmid pSG703 that contains
      the lacZ-cat expression cartridge. The lysogenic B. subtilis (phi105 MU331) was
      transformed with the resultant recombinant plasmids, and the heterologous genes
      were thereby integrated into the chromosommal DNA of B. subtilis via homologous
      recombination. The transformants were designated as B. subtilis AMY1, B. subtilis
      AMY2, B. subtilis PA1, and B. subtilis PA2, respectively. In the recombinant B.
      subtilis strains, the inserted sequences were located down stream of a strong
      phage promoter that could be activated by thermal induction. In B. subtilis AMY1
      and B. subtilis PA1, transcription of the heterologous genes was only initiated
      by the phage promoter after heat shock, whereas in B. subtilis AMY2 and B.
      subtilis PA2, transcription of the heterologous genes was initiated by dual
      promoters, the phage promoter and the native promoter. The application of dual
      promoters increased the productivity of both enzymes, with 133% enhancement for
      alpha-amylase production and 113% enhancement for penicillin acylase production.

PMID- 16607943
TI  - [The changes of rare codon and mRNA structure accelerate expression of qa-3 in
      Escherichia coli].
AB  - The key and crucial step of metabolic engineering during quinic acid
      biosynthesize using shikimic acid pathway is high expression of quinate 5
      dehydrogenase. The gene qa-3 which code quinate 5-dehydrogenase from Neurospora
      crassa doesn't express in Escherichia coli. By contrast with codon usage in
      Escherichia coli, there are 27 rare codons in qa-3, including eight AGG/AGA (Arg)
      and nine GGG (Gly). Two AGG are joined together (called box R) and some GGG
      codons are relative concentrate (called box G). Along with the secondary
      structure of mRNA analysed in computer, the free energy of mRNA changes a lot
      from -374.3 kJ/mol to least -80.5 kJ/mol when some bases in the end of qa-3 were
      transformed, and moreover, the change of free energy is quite small when only
      some bases in the box G and box R transformed. After the change of rare codon and
      optimization of some bases in the end, qa-3 was expression in E. coli and also
      the enzyme activity of quinate 5-dehydrogenase can be surveyed accurately. All
      the work above benefit the further research on producing quinic acid engineering
      bacterium.

PMID- 16607944
TI  - [Generation of selectable marker-free and vector backbone sequence-free Xa21
      transgenic rice].
AB  - The dominant gene Xa21 with broad-spectrum and high resistance to Xanthomonas
      oryzae pv. oryzae (Xoo) was transferred into C418, an important restorer line of
      japonica hybrid rice in China using double right-border (DRB) T-DNA binary vector
      through Agrobacterium-mediated transformation. 17 transgenic lines were Xa21
      positive with high resistance to the race P6 of Xoo through PCR analysis and
      resistance identification, among the total 27 independent primary transformants
      (T0) obtained. The subsequent analysis of the T1 progenies of these 17 T0 lines
      through PCR-assisted selection and resistance investigation showed that four Xa21
      transgenic T0 lines could produce selectable marker-free (SMF) progenies. The
      frequency of primary transformants producing SMF progenies was 15%. In addition,
      PCR analysis also revealed these SMF progenies did not contain vector backbone
      sequence, and they were named as SMF and vector backbone sequence-free (SMF-VBSF)
      Xa21 transgenic plants. The further molecular and phenotypic analysis of the T2
      and T3 progenies testified the homozygous SMF-VBSF Xa21 transgenic plants were
      obtained with high resistance to Xoo.

PMID- 16607945
TI  - [Introduce Tagsk1 into salt-sensitive callus to improve the capacity of salt
      tolerance by micropartical bombardment].
AB  - The Tagsk1 (Triticum asetium L. glycogen synthase kinase 1) gene derived from the
      genome of wheat salt-tolerance mutant RH8706-49 was cloned by PCR. The special
      primers designed according to full length cDNA sequence of Tagsk1 (AF525086). A
      binary expression vector pBI121-gsk1 containing Gus and Tagsk1 was constructed.
      And pBI121-gsk1 was introduced into the callus induced from mature embryos of
      salt-sensitive wheat H8706-34 and cv. China Spring by particle bombardment. The
      transformed callus were screened by Kanamycin and 0.5% NaCl. The salt-tolerance
      callus were obtained, which showed higher ability of salt-tolerance and could
      diffirentiate roots and buds on the medium containing 0.5% NaCl.

PMID- 16607946
TI  - [The analysis of heterogeneity of HWTX-I expressed in Pichia pastoris].
AB  - To seek the reason of heterogeneity of recombinant HWTX-I (rHWTX-I) expressed in
      Pichia pastoris. We expressed HWTX-I gene of interest in Pichia pastoris
      GS115/HWTX-I. The heterogenous product expressed was separated, purified and
      identified by using Ion exchange HPLC, reverse HPLC, Tricine SDS-PAGE and MALDI
      TOF Mass Spectrometry and then sequenced in both N-terminus and C-terminus. These
      results show that the heterogeneity of rHWTX-I results from the incomplete
      processing of signal peptide of N-terminus and the internal degradation of C
      terminus. Biological activity assay shows that the activity of the heterogenous
      rHWTX-I only showed 30% activity compared with the native HWTX-I. The Solutions
      to how to avoid the heterogeneity are also discussed.

PMID- 16607947
TI  - [Construction of VEGF recombinant plasmid pcDNA/V and its expression in model
      rats with acute myocardial ischemia].
AB  - The cDNA encoding human Vascular Endothelial Growth Factor 165 (VEGF165) was
      amplified using RT-PCR from human tonsil tissue and cloned into eukaryotic
      expression vector pcDNA3.1 (+). The recombinant plasmid pcDNA/V was transferred
      into 293 cells mediated by liposome and the cells stably expressing VEGF were
      selected under the pressure of G418. ELISA and Western blotting demonstrated that
      the eukaryotic expression vector pcDNA/V was successfully constructed and its
      corresponding protein could be expressed efficiently in vitro. Chick
      Charioallantoic Membrane (CAM) bioassay showed that recombinant protein has
      biological activity of hVEGF. Model rats with acute myocardial ischemia were used
      to further study the expression of VEGFin vivo. The model rats were divided
      randomly into three groups: control group, pcDNA3.1 (+) group and pcDNA/V group.
      50microL naked plasmid DNA or saline was intramyocardially injected at three
      sites into the border zone of infarction. The hearts of rats were excised and
      fixed histologically, then the infarction sizes were studied by
      immunohistochemical staining and electron microscope after four weeks.
      Immunohistochemical staining for VEGF appeared to be negative in control and
      pcDNA3.1 (+) groups. In pcDNA/V group, myocardial cells in infarction border zone
      showed positive staining for VEGF in cytoplasm. Ultrastructural anaylsis showed
      that there were visible hyperplasia of vascular endothilium in pcDNA/V group. The
      control and pcDNA3.1 (+) groups showed less capillary hyperplasia. In this study,
      VEGF165 gene was successfully cloned and its protein expressed in vitro and in
      vivo was of bioactivity, which provides a basis for the further study of
      biological functions of human VEGF.

PMID- 16607948
TI  - [Expression of human LNalpha4LG4-5 in Pichia yeast].
AB  - To carry out the secretive expression of human laminin alpha4 chain LG4-5 module
      (hLNalpha4LG4-5), recombinant expression plasmid pPICZalphaA-LG45 was constructed
      by inserting of hLNalpha4LG4-5 cDNA into yeast expression vector pPICZaA. The
      hLNalpha4LG4-5 protein was expressed in GS115 Pichia yeast strain after induced
      by methanol, and purified target protein can obviously promote the expansion and
      adhesion of 293 cells.

PMID- 16607949
TI  - [Expression of AIV subtype H5HA, H7HA and H9HA hemagglutinin gene in Pichia
      pastoris].
AB  - The expression of the hemagglutinins of Avian influenza virus H5 H7and H9
      subtypes was studied in this article by Pichia pastoris, one of the eukaryotis
      expression systems. Three reconstructed expression plasmids and engineering
      strains, named pPIC9K-H5HA, pPIC9K-H7HA, pPIC9K-H9HA and GS115/pPIC9K-H5HA,
      GS115/pPIC9K-H7HA, GS115/pPIC9K-H9HA repectively, were obtained. The
      reconstructed yeast engineering strains were identified by MD and MM plate
      selecting and PCR. The induced interests proteins were examined by SDS-PAGE and
      Western-bloting,the results showed that the interest genes were expressed
      exactly. And this will be helpful in the future study of antigen detection and
      antibody detection kit, as well in the subunit vaccines developing.

PMID- 16607950
TI  - [Molecular cloning and expression of extremely thermostable and acid-stable
      amylase gene in Pichia pastoris].
AB  - The gene encoding a extremely thermostable and acid-stable alpha-Amylase was
      amplified by PCR using hyperthermophilic archaebacterium pyrococcus furiosus
      genomic DNA as template. Then the gene was cloned into the vector of pPIC9K. The
      recombinant vector pPIC9K-amy was then transformed into E. coli DH5alpha strain.
      Sequencing test showed that the a-amylase gene cloned consisted of 1305 base
      pairs and the mature protein encoded by the gene consisted of 435 amino acids.
      The recombinant vector was transformed into chromosome of methylotrophic yeast
      Pichia pastoris GS115 strain. Regulated by the alpha-Factor, promoter of AOX1
      gene and termination signal of yeast genomic, the recombinant a-Amylase was
      expressed and excreted out of the cells. The expression of the recombinant alpha
      amylase was strictly induced by methanol. As induction time increased, the
      activity of amylase per milliliter medium went up accordingly. After 7 days
      induction, the activity of the amylase reached the max. The recombinant alpha
      amylase exhibited maximal activity at 90 to approximately 100 degrees C and at
      pHranging from 4.5 to 5.0. The enzyme is so thermostable that after disposed at
      100 degrees C for 5 hours over 60% of activity was retained.

PMID- 16607951
TI  - [Construction of human growth hormone lentiviral vector and its expression in
      murine skeletal myoblasts].
AB  - The aim of this study is to construct a lentiviral vector encoding human growth
      hormone, and to achieve the long, efficient and stable expression in murine
      skeletal myoblasts. Primary skeletal myoblasts were isolated from Sprague-Dawley
      rats and cultured by enzymatic digestion. We tested them by Desmin
      immunohistochemistry stains and found their viability was up to 94% by Trypan
      blue. Human growth hormone (hGH) cDNA was subcloned into expression vector
      pLenti6/V5-D-TOPO to construct recombinant pLenti6/V5-hGH. The pLenti6/V5-hGH and
      the contructed pLenti6/V5-EGFP were transfected into murine skeletal myoblasts by
      the Lipofectamin 2000. Through counting by the Confocal Laser Scanning
      Microscope, we identified the transfection efficency. We added the blasticidin to
      the 6-well plate with lids and obtained stable myoblasts expressing hGH. The
      concentration of human growth hormone (hGH) in cell culture medium was detected
      by Radioimmunoassay (RIA). Polymerase Chain Reaction (PCR) and DNA sequence
      showed hGH cDNA had been correctly inserted into pLenti6/V5-D-TOPO vector. Bright
      green fluorescence of the transfected cells could be observed under the Confocal
      Laser Scanning Microscope after 24 h transfection with pLenti6/V5-EGFP plasmids,
      and the transfection rate reached 40%. The difference was distinct (P < 0.01)
      between the pLenti6/V5- hGH groups and control groups in the secretive level of
      human growth hormone. After 8 weeks, the expression of human growth hormone was
      still stable. Then, we validated the biological characterization of the rhGH by
      the enzyme-link immunosorbent assay (ELISA) of the Insulin-like growth factor I
      (IGF-1). These results demonstrate we have successfully constructed the
      recombinant pLenti6/V5-hGH plasmids and accomplished rhGH long, efficient and
      stable expression ectopic in skeletal muscle myoblasts.

PMID- 16607952
TI  - [Recombinant expression and secretion of mpd gene using the promoters and signal
      peptide-encoding sequences of ytkA and ywoF gene from Bacillus subtilis].
AB  - A shuttle promoter-probe vector pNW33N-mpd was constructed with the E. coli-B.
      subtilis shuttle vector pNW33N and the mature mpd gene without it' s signal
      peptide-encoding sequence. The promoter fragments of B. subtilis ytkA and ywoF
      gene were cloned from plasmid pMPDP3 and pMPDP29 then generated the shuttle
      expression vector pNYTM and pNYWM. Expression vectors pNYTM and pNYWM were
      transformed into B. subtilis 1A751 to construct the expression strain 1A751
      (pNYTM) and 1A751 (pNYTM), in these strains, under the control of the promoters
      and signal peptides of ytkA and ywoF gene, mpd gene was expressed and secreted
      with its biological activity; the result showed that the promoter of ytkA gene is
      much stronger than that of ywoF gene. Then a new shuttle expression-secretion
      vector pYNMK was constructed using the ytkA gene promoter and the signal peptide
      encoding sequence of B. subtilis nprB gene, the expression of mpd gene achieved a
      higher level using the B. subtilis WB800 as the host, the methyl parathion
      hydrolase activity accumulated to a maximum level of 10.40 u/mL after 84 h of
      cultivation at the late stationary phase, which was 10.8-fold higher than the
      expression level of the original Plesiomonas strain M6, about 91.4% of the
      recombinant expression production was secreted into the culture medium.

PMID- 16607953
TI  - [Effect of straw apoplast protein on cellulase activity].
AB  - We studied the alteration of the maize straw apoplast proteins in the process of
      preservation, and analyzed the effects of apoplast proteins on Penicillum
      expansum cellulase activities. The results show that: the extractable apoplast
      proteins are gradually decreased during the preservation of maize straw.
      Meanwhile, their synergistic effects on P. expensum cellulose are also
      attenuated. The apoplast proteins extracted from fresh maize straw possess
      endogenous EG activities, which is unstable and completely vanished after 6
      months preservation. The apoplast proteins from the preserved straw exhibit
      significant synergistic effect on FPA, cotton lyase and beta-glucosidase. The
      maximal synergistic values are 95.32%, 102.06% and 96.6%, respectively. But
      interestingly, they inhibit the CMCase activity (max. 49.52%). Apoplast proteins
      show distinctive synergy with betaG and EG, but have no effect on CBH activity.
      After eliminating the effect of endogenous EG, the apoplast proteins from fresh
      maize straw have enhanced synergistic or inhibiting effects on FPA, Cotton lyase,
      betaG and CMCase than those extracted from the preserved straw. Based on our
      observation, the apoplast proteins play important roles in regulating the
      cellulase activities. The detailed analysis of the related mechanisms will
      greatly benefit the studies of the natural biomaterials hydrolysis.

PMID- 16607954
TI  - [Study on the asexual sporulation of Aspergillus niger under blue light induction
      and analysis of its subtractive library].
AB  - The effect of blue light (BL) on the morphological development of Aspergillus
      niger was studied by the scanning electron microscopy (SEM) observation.
      Comparing with the darkness, BL was able to stimulate development of
      sporangiophore and conidiosphore, promote grownth of mycelium. Suppression
      subtractive hybridization (SSH) was conducted with tester cDNA which was from 39
      to approximately 40h-old mycelium cultured under darkness and driver cDNA which
      was from mycelium illuminated for 3 to approximately 4h under BL after dark
      growth. Some cDNA bands were obtained by suppression PCR (polymerase chain
      reaction) with the subtractive cDNA. Positive bacterial clones were randomly
      picked and identified by colony PCR method. Through sequence alignments from
      GenBank, most of differential cDNA fragments were highly identical with some
      redox enzymes existing in mitochondria, and the quantitative measurement of these
      differential mRNA by real time RT-PCR indicated that relative expression of the
      identified gene fragments under BL induction was higher than that under darkness.
      Furthermore, the result suggested that some respiratory chain redox enzymes of
      mitochondria were involved in the photoresponse and consequently influence the
      metabolism. Among differential cDNA fragments two unkown sequences were found and
      their complete gene and gene function remained to be investigated.

PMID- 16607955
TI  - [Effect of feeding pre-L-methionine on high-cell-density fermentation for S
      adenosyl-L-methionine production].
AB  - The yield of S-adenosyl-L-methionine (SAM) by saccharomyces cerevisiae
      fermentation was affected by the strategy of feeding L-methionine. The effects
      that feeding strategies and the amount of precursor L-methionine had on the
      production of SAM by saccharomyces cerevisiae G14 were investigated. The results
      showed that feeding L-methionine could obviously improve the accumulation of SAM,
      and both the biomass and SAM yield relied heavily on different feeding
      strategies. In our work, it was found that total amount of L-methionine added
      should be no less than 0.7g per 10 grams of dry cell weight. Five different
      feeding strategies had been investigated in our experiment, and such comparison
      indicated that favorable results could be achieved as the biomass reached the
      status of high cell density (120g/L). If 9 grams of the precursor L-methionine
      was introduced once and for all, the accumulation of SAM reached maximum of
      4.31g/L at the 18th hour after addition; if the precursor amino acid was fed at a
      rate of 2g/h in 5 h, maximum yield of 4.98g/L was achieved at the 28th hour after
      feeding. Thus high cell density fermentation can be successfully applied to SAM
      production by Saccharomyces cerevisiae with the consequence of over 130g/L of
      biomass gained using the above two strategies.

PMID- 16607956
TI  - [Detection of intracellular reactive oxygen species by flow cytometry in Pichia
      pastoris fermentation].
AB  - In Pichia pastoris fermentation, methanol was oxidized into carbon oxide and
      produced a byproduct H2 O2, one of the partially reduced forms of molecular
      oxygen known as reactive oxygen species (ROS) . ROS are highly damaging towards
      cellular constituents. Flow cytometry (FCM) is an excellent method that permits
      the rapid, optical analysis of individual cells and has many advantages over
      conventional cytometry. However, its use in detecting intracellular ROS levels
      during Pichia fermentation was rarely reported. In our work, by means of flow
      cytometry, two fluorescent dye 2', 7'-dichlorofluorescin diacetate (DCFH-DA) and
      propidium iodide (PI) were used to detect ROS. The effect of intracellular ROS on
      Pichia pastoris cells during fermentation was studied through the comparison
      between DCFH-DA/PI double-stained cells and PI single-stained cells. In this
      study, the loss of cell viability during fermentation was correlated with the
      accumulation of ROS. At the glycerol batch and fed-batch phase, little ROS was
      accumulated intracellularly and cell viability reached almost 100%. At the early
      methanol fed-batch phase, intracellular ROS accumulation took place but 98.5%
      cells still kept viable. At the later methanol fed-batch phase, 94.0% cells
      accumulated high ROS. As a result, some cells lost their viability because of the
      damage of ROS. 25.4% dead cells accumulated high ROS in the total 29.1% dead
      cells.

PMID- 16607957
TI  - [Development of a new hydrophobic interaction chromatography absorbent and its
      application to the purification of recombinant hepatitis B surface antigen].
AB  - A new hydrophobic absorbent based on homemade highly cross-linked agarose beads
      was synthesized by immobilizing butyl derivative onto the matrix linkage. The
      density of ligand was controlled by adjusting the concentration of butanethiol
      and the synthesis route was optimized by evaluating the purification efficiency
      of recombinant Hepatitis B surface antigen (HBsAg) expressed by Chinese hamster
      ovary (CHO) cell line. A high performance absorbent was finally screened out with
      up to 80% of HBsAg recovery and purification-fold (PF) about 20. Furthermore, the
      column pressure was about 0.06 MPa under the flow rate of 500cm/h, and no leaked
      butyl were detected after exposing the gel in common buffers, chaotropic agents,
      high concentrations of denaturing agents such as guanidine hydrochloride, urea
      and polar organic solvents. These results demonstrated that the absorbent have
      high physico-chemical stability, so it was available for the downstream process.
      Finally, after scaled up to 2L wet gel/batch, the absorbent was applied to the
      integration of three-step chromatography and obtained the purified CHO-HBsAg with
      95% purity by SDS-PAGE and HPLC, which meet the requirements of SFDA. The
      purification efficiency and the reproducible ability of the absorbents were also
      evaluated from batch-to-batch. The results demonstrated that the absorbent met
      the requirement of scalable, reproducible, economic effect as well. This
      absorbent is a promising alternative exported HIC gel for wildly being used in
      Chinese pharmaceutical industries.

PMID- 16607958
TI  - [Preparation of recombinant HIV-TATm-survivin (T34A) protein and its pro
      apoptosis activity to cancer cells in vitro].
AB  - As a novel member of the IAP (Inhibitor of apoptosis protein) family, survivin
      was observed to be expressed in most human cancerous cells. Fusion protein TATm
      survivin (T34A) has drawn considerable attention because it is a potential anti
      tumor protein that can be transduced into cancer cell with the help of HIV-TAT
      domain. In this study, the cDNA encoding survivin was cloned by RT-PCR from human
      breast cancer cell lines B-Cap-37. An expression vector of pRSET-B-HIV-tatm
      survivin (T34A) was constructed by PCR after survivin (T34A) was mutated by site
      directed mutagenesis. Subsequently, the resultant plasmid was transformed into E.
      coli BL21 (DE3). Recombinant HIV-TATm-Survivin (T34A) protein was expressed
      efficiently with 0.5mM IPTG as inducer, reaching a yield of 650mg/liter (as
      inclusion body) in fermentation culture. The inclusion bodies were solubilized,
      refolded and purified to a purity of 96% by ion exchange chromatograghy and size
      exclusion chromatography. Remarkable effects of the purified recombinant HIV-TATm
      Survivin (T34A) on the morphology of cell line SW1990 and B-Cap-37 were observed
      after being administrated for 4h. MTT assay showed recombinant HIV-TATm-survivin
      (T34A) protein could inhibit significantly cell proliferation of SW1990 and B-Cap
      37 and SSMC-7721 in vitro. Apoptosis rate and cell circle of SW1990 and B-Cap-37
      that had been treated with target protein (final concentration 30 microg/mL) were
      detected with flow cytometry. Results revealed that more than 65% cancer cells
      were arrested at G1 phase. The study suggested that TATm-survivin (T34A) protein
      was a hopeful protein drug in the treatment of cancers by facilitating apoptosis
      of cancer cells. Key words recombinant HIV-TATm-Survivin (T34A), expression and
      purification, pro-apoptosis bioactivity, SW1990 and B-Cap-37 cancer cell lines

PMID- 16607959
TI  - [A study on the discrimination of thermophilic and mesophilic proteins based on
      dipeptide composition].
AB  - In this work, the dipeptide composition of 3216 thermophilic and 4007 mesophilic
      protein sequences was systematically analyzed. We found that the thermophilic
      proteins contained more dipeptides such as EE, EK, KE, VE, EI, KI, EV, KK, VK and
      IE, whereas less dipeptides such as AA, LL, LA, AL, QA, QL, AQ, LT, TL and EQ.
      Based on this information, a statistical method for discriminating thermophilic
      and mesophilic proteins was developed. Our approach correctly picked up the
      thermophilic proteins with the accuracy of 94.0% and 89%, respectively, for the
      testing sets of 382 and 73 thermophilic proteins. And for the testing 325 and 73
      mesophilic proteins, the accuracy was 85.2% and 89%, respectively. The influence
      of specific dipeptides on discrimination was also discussed.

PMID- 16607960
TI  - [Significant improved anthocyanins biosynthesis in suspension cultures of Vitis
      vinifera by process intensification].
AB  - The low-production is a ubiquitous problem and has prevented the
      commercialization of secondary metabolite production in plant cell culture. In
      order to examine the effective approaches to improvement of secondary metabolite
      production in plant cell culture, the investigation of anthocyanins accumulation
      in suspension cultures of Vitis vinifera, as a model system, had been initiated
      in our laboratory. In this present research, various elicitors and the precursor
      of phenylalanine were used in combination to enhance the anthocyanins production
      in suspension cultures of Vitis vinifera. And an integrated process with the
      combination of elicitation, precursor feeding and light irradiation was reported
      for rational bioprocess design. Among the combination treatment of phenylalanine
      feeding and several elicitors (methyl-beta-cyclodextrin, dextran T-40, methyl
      jasmonate, extracts of Aspergillus niger and Fusarium orthoceras), the
      combination with methyl jasmonate gave the highest anthocyanins production in
      suspension cultures of Vitis vinifera. When compared to the controls, the
      anthocyanins content (CV/g, FCW) and production (CV/L) increased by 2.7-fold and
      3.4-fold, respectively. The optimum time for the addition of phenylalanine and
      methyl jasmonate was 4 days after inoculation. Two cell lines with different
      anthocyanins-producing capacity responded differently to the optimum combination
      treatment of 30 micromol/L phenylalanine feeding, 218 micromol/L methyl jasmonate
      elicitation and 3000 to approximately 4000 1x light illumination. The high-and
      low-anthocyanins-producing cell lines of VV05 and VV06 produced the maximum of
      2975 and 4090 CV/L of anthocyanins that were 2.5- and 5.2-fold of the controls,
      respectively.

PMID- 16607961
TI  - [The application of co-culture system on the in vitro development of bovine
      somatic nuclear transferred embryos].
AB  - To establish a co-culture system of nuclear transferred embryos in bovine,
      effects of co-culture cell types, passages and cryopreservation as well as
      addition of BFF or FBS were investigated. The results showed that embryos co
      cultured with oviductal epithelial cell and granulosa cell achieved significantly
      higher blastocyst rate compared with the control group (P < 0.05) and co-cultured
      with oviductal epithelial cell had more embryo cell number than those with
      granulosa cell. Passages of co-culture cells significantly affected the
      blastocyst rate and embryo cell number (P < 0.05), and cryopreservation decreased
      the blastocyst rate and embryo cell number remarkably. Supplemention of BFF
      increased blastocyste rate significantly (P < 0.05). In conclusion, co-cultured
      with fresh primary oviductal epithelial cell along with addition of 10% BFF in
      SOFaa could improve development of nuclear transferred bovine embryo in vitro.

PMID- 16607962
TI  - [The effect of induction temperature on aggregation of consensus interferon-alpha
      expressed by Pichia pastoris].
AB  - The effect of induction temperature on aggregation of consensus interferon-alpha
      expressed by Pichia pastoris was investigated. The cell growth and cIFN level
      were analyzed and compared when Pichia pastoris was grown at 30,25,20 degrees C
      during induction phase, using 5.0L fermentor. The result suggested that the cell
      growth was not affected much under the different induction temperature, but the
      protein level declined markedly with the decrease of the induction temperature.
      The total protein ammount induced at 20 degrees C was 67.8 percent of that at 30
      degrees C. SDS-PAGE and native-PAGE as well as Western blotting analysis were
      further conducted. The electrophoresis results revealed that cIFN formed
      aggregates after secreted into media when protein was induced at 30 degrees C but
      this problem can be restored by decreasing the induction temperature to 20
      degrees C. cIFN monomer in supernatant arrived at 570mg/L and bioactivity of
      fermentation broth reached 1.05 x 10(9) IU/mL at 20 degrees C of induction
      temperature. The amount of cIFN monomer and bioactivity in supernatant elevated
      7.2 and 38.7 times, respectively, when the induction temperature was controlled
      at 20 degrees C instead of conventional 30 degrees C.

PMID- 16607963
TI  - [Effects of temperature on the kinetics and level of energy charge and oxidation
      reduction state in pyruvate biosynthesis].
AB  - Temperature plays an important role in pyruvate biosynthesis by Torulopsis
      glabrata 620. The effects of temperature on the substrate consumption, cell
      growth, pyruvate biosynthesis and level of energy charge and oxidation-reduction
      state have been investigated. During the constant temperature fermentation,
      higher temperature can enhance the rate of glucose consumption, cell growth and
      pyruvate production. However, it also leads to higher energy charge in the
      prophase of fermentation, too much consumption of glucose by cell and deficient
      throughput of pyruvate in the anaphase of fermentation, which brings on decrease
      of pyruvate yield. Oppositely, maintaining lower temperature during the
      fermentation can offer constant production capacity of pyruvate in the anaphase
      of fermentation. But the disadvantages are lower cell growth and higher level of
      NADH/NAD+ in vivo during the anaphase of fermentation, which leads to lower
      productivity inevitably. Disaccords above-mentioned indicate that the higher
      production, higher yield and higher productivity cannot be achieved at one time
      during a constant temperature fermentation.

PMID- 16607964
TI  - [Research of the feeding strategy in the fermentation of recombinant human
      fibreblast growth factor mutant].
AB  - Human acidic fibreblast growth factor (haFGF) was a kind of cell growth factor
      with wide bio-activity on cell from mesectoderm and neuro-ectoderm.In this paper,
      the effect of acetate concentration on the growth and expression of recombinant
      human acidic fibroblast growth factor mutant system E.coli BL21(DE3)/pET3C-haFGF
      was investigated. Four fed-batch modes: batch-fed, batch-DO static balance, DO
      static balance-glucose starvation, and pH-static state were investigated. The
      accumulation of acetate during the fermentation course was effectively inhibited.
      The OD600nm value was about 22, after purification, the soluble rhaFGF yielded
      450mg/L. During the fermentation, no special ways such as pure oxygen, pressure
      were adopted, thus the established process would be easily scaled up for industry
      purpose.

PMID- 16607965
TI  - [Inhibitory effect of new antimicrobial substance by Bacillus subtilis fmbJ on
      Newcastle disease virus and infectious Bursal disease virus in vitro].
AB  - The resistance effect on Newcastle disease virus (NDV) and Infectious Bursal
      Disease Virus(IBDV) in vitro of a new antimicrobial substance (AS), which
      produced by a Bacillus subtilis strain named B. subtilis fmbJ. Results showed
      that the TD50 and TD0 value of this AS on Chicken Embryo Fibroblasts cell (CEF)
      were 128.95mg/L and 25.79mg/L, respectively. This AS could strongly inhibit the
      cytopathic effects of cell induced by NDV as well as IBDV, and increase the
      survival rate of cell remarkably. This AS could inhibit the function of NDV and
      IBDV, and it could defend against the infection and inhibit multiplication of NDV
      and IBDV, and the effect was the same as the antiviral medicine Ribavirin. It had
      lower toxicity to CEF cell, therefore we would study it further that it was as
      antiviral medicine.

PMID- 16607966
TI  - [A review on genetic testing].
AB  - Nowadays genetic tests are available in a growing number of countries, for an
      expanding set of conditions. Nonetheless, many Chinese people are still not
      familiar with the principle, testing types, technologies used in this process,
      application and benefits to society, and national or international administration
      of genetic testing. It is essential that this increased use of genetic testing
      should be accompanied by appropriate oversight. This article has roughly reviewed
      the proceeding of genetic testing these years, which will help us learn more
      about the new coming era of human genetics and molecular medical revolutions.

PMID- 16607967
TI  - Genital herpes vaccines--cause for cautious optimism.
AB  - The high prevalence of herpes simplex virus infections in many communities, its
      numerous serious physical and psychological complications and its importance in
      enhancing the transmission of HIV make this virus an obvious target for
      prevention by vaccination. Randomised clinical trials of only one genital herpes
      vaccine has shown efficacy so far. Analysis of clinical results is complicated by
      the difference between disease and infection, different results for males and
      females and the interaction between HSV-1 and HSV-2 immunity.

PMID- 16607968
TI  - Current issues in the use of colposcopy for examination of sexual assault
      victims.
AB  - Colposcopic examination is considered the gold standard in child sexual abuse
      evaluations in Australia. However, there remain contentious issues with its use,
      especially in adult victims, which we sought to address by a review of the
      literature. Colposcopy has been shown to be a sensitive and acceptable tool for
      detection of anogenital abnormalities in children. The significance of some
      genital findings remains controversial, especially when images are interpreted by
      inexperienced clinicians. Its use in adult assessments is hampered by a lack of
      comparative studies on colposcopically detected genital injuries in adults
      following consensual v. non-consensual sexual intercourse. Further research is
      urgently needed before the use of colposcopy can be routinely recommended for
      adult victims.

PMID- 16607969
TI  - Prevalence and typing of human papilloma virus (HPV) among female sex workers and
      outpatient women in southern Thailand.
AB  - BACKGROUND: Thai sex workers (SW) have high rates of sexually transmitted
      infections (STIs); however, detection and treatment is often complicated by
      accessibility to sensitive and accurate diagnostic tests. Self-sampling of women
      combined with molecular amplification techniques could help in accurate
      diagnosis, treatment and follow-up of such women. Detection of persistent high
      risk human papilloma virus (HPV) in such populations could also be beneficial in
      identifying women who may need more frequent follow-up for cervical cytology
      screening. The current study aimed to examine the prevalence of HPV in this
      population and compare this with the lower-risk outpatient women (OPW) in
      Thailand. METHODS: Four hundred and thirty OPW and 524 Thai SW were sampled by a
      self-administered tampon collection. Cells were extracted from tampons and,
      subsequently, women underwent routine vaginal examination for detection of other
      STIs. Detection of HPV was performed by polymerase chain reaction (PCR) using the
      L1 consensus primers, followed by L1 consensus probe using an in-house PCR-enzyme
      linked immunosorbent assay (ELISA). All positive samples were typed using PCR
      ELISA and type-specific oligonucleotide probes. RESULTS: Overall, HPV was
      detected in 20/430 (4.6%) and 120/524 (22.9%) in OPW and SW respectively. Over
      98% of samples produced a beta-globin signal, indicating adequately collected
      samples. Human papilloma virus typing probes detected HPV16 or 18 in 14% and 26%
      of the positive samples from OPW and SW respectively. HPV31, 33, 35 or 39 were
      detected in 19% and 12% and HPV45, 51 or 52 in 9.5% and 4% of positive OPW and SW
      patients respectively. Low risk HPV6 or 11 were detected in 1% and 4.9% of OPW
      and SW respectively. CONCLUSION: There was a significantly higher HPV prevalence
      in Thai SW than OPW, with the majority (21%) of positive samples containing the
      oncogenic HPV16 or 18 DNA. The results indicate that PCR could serve as a rapid
      and easy method for identification of women who require more frequent screening
      for cervical cancer.

PMID- 16607970
TI  - Chlamydia trachomatis infection in the family planning clinical setting across
      New South Wales.
AB  - BACKGROUND: Following a small pilot study in 2003, a study was set up to
      determine the prevalence of genital Chlamydia trachomatis infection in young
      women presenting to Family Planning NSW centres across New South Wales and to
      evaluate the characteristics of those infected. METHODS: A cross-sectional survey
      of 621 consecutive women aged from 16 to 24 years was carried out over a 3-month
      period in 2004 at five Family Planning NSW centres. Urine samples were tested for
      C. trachomatis using the polymerase chain reaction (PCR) method. Women with a
      positive result were reviewed and treated. RESULTS: Of 925 eligible clients, 621
      (67%) were recruited to the study. Chlamydia trachomatis was detected in 35 of
      the 621 recruits (5.6%, 95% CI 3.8-7.4). The prevalence at the Hunter centre was
      significantly higher than the combined prevalence at the other four participating
      centres (9.7% compared with 3.9%; P = 0.008). Two characteristics were identified
      as independent predictors of infection in this study: 'reporting a recent change
      ofpartner in the past three months' (crude odds ratio (OR) 3.33, 95% CI 1.67
      6.64) and 'reporting three or more partners in the past year' (crude OR 3.69, 95%
      CI 1.83-7.46). Reported condom use, a history of one or more sexually
      transmissible infections and current combined oral contraceptive pill use were
      not associated with infection in this study. CONCLUSIONS: The prevalence of C.
      trachomatis infection is sufficiently high to support targeted testing of 16-24
      year-old women in the Family Planning NSW setting and informs the development of
      a national screening strategy.

PMID- 16607971
TI  - Listening to female sex workers in Vietnam: influences on safe-sex practices with
      clients and partners.
AB  - BACKGROUND: This qualitative study assessed HIV/AIDS knowledge and frequency of
      and influences on condom use with clients and regular, non-client partners among
      female sex workers (FSWs) in Khanh Hoa, a tourist-oriented province of central
      Vietnam where sex work is common. METHODS: Data were collected via semi
      structured interviews with indirect (n = 16) and direct (n = 9) FSWs. RESULTS:
      Although the majority of respondents were well informed about HIV/AIDS
      transmission, about one-third had inaccurate beliefs about HIV-positive people as
      well as the mechanisms by which HIV is transmitted from mother to child. Condom
      use was inconsistent. More direct than indirect FSWs reported using condoms most
      of the time with clients but none used condoms all the time. With regular
      partners, most respondents reported that they never used condoms. Around one
      third of women hid their sex work from their regular partners, who made the
      decision to use or not to use condoms. The most frequently reported reasons for
      not using condoms with clients were because clients offered a higher price,
      clients insisted on condom-free sex, and possession of condoms as evidence of sex
      worker status. For regular partners, the reasons were familiarity, condom use
      being dependent on partner's decision, and condom use as evidence of sex worker
      status. There was no apparent relationship between HIV knowledge, time in sex
      work, and safe sex practices. CONCLUSION: Recommendations are made to improve the
      rate of condom use among FSWs.

PMID- 16607972
TI  - Early clinical experience with atazanavir in treatment-experienced patients.
AB  - BACKGROUND: Atazanavir (ATV) is a newly approved protease inhibitor following
      successful clinical trials in naive and treatment-experienced patients. We
      describe early experience with ATV in treatment-experienced patients attending a
      single ambulatory care clinic in Sydney. METHODS: Patients commencing ATV between
      February 2003 and May 2004 in an expanded access program were identified from the
      clinic pharmacy's database. Data were retrospectively collected from patients'
      medical records. RESULTS: Data from 30 patients were analysed. Reasons for
      commencing ATV were: virological failure in six patients (20%); toxicity to
      previous regimen in 13 patients (43%); simplification strategy in two patients
      (7%); and recommencing therapy in nine patients (30%) following treatment
      interruption. Six patients (20%) discontinued ATV. One patient discontinued ATV
      due to virological failure, two patients discontinued due to toxicity to
      concomitant antiretrovirals, two as a result of the patient's choice and one as a
      result of the physician's decision. Eighteen patients commenced ATV in
      combination therapy with a detectable viral load (VL). From a baseline VL of 4.3
      +/- 1.1 log10 copies mL(-1), 15 (83%) had > 1.0 log decrease in VL with 11 (61%)
      achieving viral suppression (<50 copies mL(-1)). Three (16%) failures were
      recorded in this group. Twelve subjects commenced ATV with an undetectable VL.
      One failure was recorded in this group. Bilirubin increased by 22.7 micromol L(
      1) (P < 0.001), with significant decreases in cholesterol (1.4 mmol L(-1), P =
      0.01) and triglycerides (1.5 mmol L(-1), P = 0.01) in 12 patients on ritonavir
      boosted ATV. CONCLUSION: This audit found ATV to be safe, well tolerated and had
      good potency in treatment-experienced patients. However caution should be
      exercised in switching to ATV in heavily pre-treated patients.

PMID- 16607973
TI  - Estimating population distribution and HIV prevalence among homosexual and
      bisexual men.
AB  - OBJECTIVES: To estimate the extent of the homosexual and bisexual male population
      in inner Sydney and HIV prevalence within this population. METHODS: Data from the
      2000/2001 Sydney Gay Community Periodic Survey (SGCPS) and the Australian Study
      of Health and Relationships were used. RESULTS: A re-analysis of responses from
      men in some inner east and inner west postcode areas of Sydney indicated that:
      the proportion of men who identified as homosexual or bisexual ranged from 4.4%
      to 48.1%; from 9.8% to 51.5% of men reported same-sex experiences during their
      lifetime; and 12.9% to 52.8% of men had ever experienced feelings of same-sex
      attraction. HIV prevalence among respondents to the SGCPS in these same areas
      varied from 9.1% to 21.3%. CONCLUSION: These findings indicate elevated
      proportions of men with same-sex identity, experience or attraction living in
      these inner Sydney locations compared with other geographic areas and illustrate
      how gay communities cluster.

PMID- 16607974
TI  - Risk factors for HIV seroconversion in homosexual men in Australia.
AB  - BACKGROUND: Rates of newly acquired HIV infection are increasing in Australia,
      and sexual contact between men accounts for 85% of cases. OBJECTIVE: To
      investigate behavioural risk factors for HIV seroconversion among gay and
      bisexual men from Sydney and Melbourne, Australia. METHODS: 103 men with newly
      acquired HIV infection were recruited from clinics in Sydney and Melbourne and
      behavioural risk factor questionnaires were administered between January 2003 and
      October 2004. Results were compared with a cross sectional and a cohort study
      performed by our group that enrolled similar populations of men. RESULTS: The
      majority of seroconverters (73%) reported more than five sexual partners in the
      last six months. Ninety-five men (92%) were able to identify a high-risk event
      (HRE) that they thought had led to their HIV seroconversion. Most (70%) reported
      receptive unprotected anal intercourse (UAI), insertive UAI, or both at their
      HRE. Sixteen men (16%) reported no UAI in the preceding six months including the
      HRE. Men were more likely to report receptive UAI at their HRE when they
      perceived a partner to be HIV-negative as compared with when they perceived a
      partner to be HIV-positive (P = 0.05). Injection drug use was reported by 22% of
      the men in the previous six months, and 62% reported intoxication with alcohol (>
      or =5 drinks) or mood altering recreational drug use at the HRE. CONCLUSIONS: Gay
      and bisexual men who have recently seroconverted are highly sexually active and
      report high rates of unprotected anal intercourse and recreational drug use at
      the HRE.

PMID- 16607975
TI  - The price of guidelines: revising the national guidelines for managing Australian
      women with abnormal pap smears.
AB  - Australia utilises nationally approved guidelines for managing women with
      abnormal Pap smears. The guidelines were recently revised using the process
      designated by the National Health and Medical Research Council. Revising the
      guidelines was protracted and controversial. This paper explores the reasons for
      the difficulties encountered and queries the cost of undertaking such work.

PMID- 16607976
TI  - Age of sexual initiation and HIV-related behaviours: application of survival
      analysis.
AB  - Previous studies have consistently suggested positive associations between early
      sexual initiation and subsequent risky sexual behaviours, HIV/STD infection,
      adolescent pregnancy and substance use. In the present study, survival curves for
      rural-to-urban migrants in China with and without HIV-related behaviours were
      analysed to determine (1) the risk of initiating sex at each ageand (2) the
      association between sexual initiation and HIV-related behaviours.

PMID- 16607977
TI  - Was this a result you were expecting?

PMID- 16607978
TI  - Photon correlation and scattering: introduction to the feature issue.
AB  - This special issue of Applied Optics contains research papers on photon
      correlation and scattering, many of which were presented at the OSA Topical
      Meeting that was held 16-18 August 2004.

PMID- 16607979
TI  - Gradient-driven fluctuations experiment: fluid fluctuations in microgravity.
AB  - We describe an experimental breadboard developed for the investigation of
      nonequilibrium fluctuations induced by macroscopic temperature and concentration
      gradients under microgravity conditions. Under these conditions the amplitude of
      the fluctuations diverges strongly for long wavelengths. The setup was developed
      at the University of Milan and at the University of California at Santa Barbara
      within the gradient-driven fluctuations experiment (GRADFLEX) project of the
      European Space Agency, in collaboration with the National Aeronautics and Space
      Administration. The apparatus uses a quantitative shadowgraph technique for
      characterization of the static power spectrum of the fluctuations S(q) and the
      measurement of their dynamics. We present preliminary experimental results for
      S(q) obtained in the presence of gravity for gradient-driven fluctuations for two
      cases, those induced in a liquid mixture with a concentration gradient produced
      by the Soret effect and those induced in a single-component fluid by a
      temperature gradient.

PMID- 16607980
TI  - Use of dynamic schlieren interferometry to study fluctuations during free
      diffusion.
AB  - We used a form of schlieren interferometry to measure the mean-squared amplitude
      and temporal autocorrelation function of concentration fluctuations driven by the
      presence of a gradient during the free diffusion of a urea solution into water.
      By taking and processing sequences of images separated in time by less than the
      shortest correlation time of interest, we were able to simultaneously measure
      dynamics at a number of different wave vectors. The technique is conceptually
      similar to the shadowgraph method, which has been used to make similar
      measurements, but the schlieren method has the advantage that the transfer
      function is wave-vector independent rather than oscillatory.

PMID- 16607981
TI  - Surface response functions for a thin-film between fluids with infinite
      boundaries and for a fluid-fluid interface between finite boundaries.
AB  - Measuring the surface response function of a fluid allows us to ascertain many of
      its properties. Simplified surface response functions are presented for several
      interface conditions, including (a) a thin-film between two fluids of infinite
      extent, (b) the newly derived fluid-fluid interface between finite boundaries,
      and (c) the traditional fluid-fluid interface between infinite boundaries. The
      finite-boundary derivation indicates that wall effects are very short range. This
      portends that the effects of external vibrations, which traditionally make this
      measurement challenging, can be mitigated by scattering from thin fluid layers.

PMID- 16607982
TI  - Particle-size and velocity measurements in flowing conditions using dynamic light
      scattering.
AB  - The noninvasive optical technique of dynamic light scattering (DLS) is routinely
      used to characterize dilute and transparent submicrometer particle dispersions in
      laboratory environments. A variety of industrial and biological applications
      would, however, greatly benefit from on-line monitoring of dispersions under
      flowing conditions. We present a model experiment to study flowing dispersions of
      polystyrene latex particles of varying sizes under varying flow conditions by
      using a newly developed fiber-optic DLS probe. A modified correlation function
      proposed in an earlier study is applied to the analysis of extracting the size
      and velocity of laminar flowing particulate dispersions. The complementary
      technique of laser Doppler velocimetry is also used to measure the speed of
      moving particles to confirm the DLS findings.

PMID- 16607984
TI  - Gaussian and non-Gaussian speckle fluctuations in the diffusing-wave spectroscopy
      signal of a coarsening foam.
AB  - All previous applications of diffusing-wave spectroscopy to aqueous foams have
      relied on the assumption that the electric field of the detected light is a
      Gaussian random variable and hence that the Siegert relation applies. We test
      this crucial assumption by simultaneous measurement of both second- and third
      order temporal intensity correlations. We find that the electric field is
      Gaussian for typical experimental geometries equivalent to illumination and
      detection with a plane wave, both for backscattering and transmission through an
      optically thick slab. However, we find that the Gaussian character breaks down
      for point-in-point-out backscattering geometries in which the illumination spot
      size is not sufficiently large in comparison with the size of the intermittent
      rearrangement events.

PMID- 16607983
TI  - Near-field microwave microscope and electron-spin-resonance detection: ruby
      crystal surface.
AB  - Microwave photons can image a surface by using near-field geometry with spatial
      resolution close to the nanometer-length scale. We detected electron-spin
      resonance (ESR) on ruby surfaces by using microwave photons at the S-band
      frequency (3.73 GHz). The spatial locations of the electron-spin centers were
      pinpointed with localized incident microwave photons generated by using
      evanescent microwave microscopy (EMM). We show that the EMM probe is capable of
      resolving 20,000 spin transitions, compared with the approximately 10(10) minimum
      detectable spins of the conventional continuous-wave ESR spectrometer. This
      represents roughly a 6-order-of-magnitude enhancement in sensitivity. Our
      ultimate goal is to achieve the minimum detectable spin transition of a single
      electron and nanometer-level spatial resolution by using microfabricated atomic
      force microscopy-EMM probes.

PMID- 16607985
TI  - Fuzzy simultaneous measurement of two polarization vector components.
AB  - The advent of quantum computers threatens the security of conventional encryption
      schemes (e.g., those based upon the excessive amount of computational time that
      might be required to guess your password). Quantum encryption is intended to
      restore the security by basing it instead upon the impossibility of the
      simultaneous measurement of two noncommuting operators. I derive a measurement
      associated with the angular momentum lowering operator, which describes a
      simultaneous (yet realizable) measurement of two noncommuting spin-vector
      components. Correlations between two such detectors are also discussed and
      compared with the conventional Stern-Gerlach results.

PMID- 16607986
TI  - Direct determination of the number-weighted mean radius and polydispersity from
      dynamic light-scattering data.
AB  - We compare results for the number-weighted mean radius and polydispersity
      obtained either by directly fitting number distributions to dynamic light
      scattering data or by converting results obtained by fitting intensity-weighted
      distributions. We find that results from fits using number distributions are
      angle independent and that converting intensity-weighted distributions is not
      always reliable, especially when the polydispersity of the sample is large. We
      compare the results of fitting symmetric and asymmetric distributions, as
      represented by Gaussian and Schulz distributions, respectively, to data for
      extruded vesicles and find that the Schulz distribution provides a better
      estimate of the size distribution for these samples.

PMID- 16607987
TI  - Study of smoke aerosols under a controlled environment by using dynamic light
      scattering.
AB  - The size of cigarette smoke aerosols was determined with the photon-correlation
      technique. The effects of temperature and concentration on aerosol size were also
      observed. We found that aerosol size increases almost linearly with an increase
      in concentration but decreases with an increase in temperature.

PMID- 16607988
TI  - Measurement and analysis of angle-resolved scatter from small particles in a
      cylindrical microchannel.
AB  - Scatter of a two-dimensional Gaussian beam of a rectangular cross section by
      individual particles suspended in a fluid in a cylindrical channel is modeled by
      using a full-wave approach. First, the internal and scattered fields associated
      with the cylindrical channel and the two-dimensional Gaussian beam are computed.
      The spatial variations of the computed electromagnetic field inside the channel
      indicate that particles and cells of sizes relevant to flow cytometry are
      subjected to essentially plane-wave illumination, and hence Lorenz-Mie theory is
      applicable for spherical particles. Further, it is assumed that the perturbation
      of the electromagnetic field in the channel that is due to the presence of a
      particle is negligible, allowing us to ignore the interactive scatter of the
      particle and the channel (they are electromagnetically uncoupled). This
      approximation is valid when the particle intercepts a small fraction of the total
      energy inside the channel and when the particle or cell has a low relative
      refractive index. Measurements of scatter from the channel agree with the
      analytical model and are used to determine the location of detectors to measure
      scatter from particles in the channel. Experimental results of accumulated
      scatter from single latex spheres flowing in the channel show good agreement with
      computed results, thereby validating the internal field and uncoupled scatter
      models.

PMID- 16607989
TI  - Polar nephelometer based on a rotational confocal imaging setup.
AB  - Rapid measurement of the angular distribution of light scattered by particles,
      the scattering phase function, is achieved by using a new type of polar
      nephelometer, a device for measuring the angular scattered-light intensity
      distribution, with a high angular precision and across many orders of magnitude
      of intensity. The design offers high-speed measurements and avoids many of the
      problems often associated with traditional goniometers when they are used for
      measurements of light scattering from small particles or biological cells in
      suspension. Our system relies on confocal imaging of the test space with off-axis
      parabolas, using a rotating mirror to scan the angular field of view at the
      second focus of a pair of conjugated parabolic mirrors, with the test space
      located at the first focus. The angular resolution of the system is limited
      mainly by the data-acquisition sampling frequency. In this proof-of-principle
      demonstration the system performs multiple scans of a 55 deg field of view in a
      very short time (<1 s). To significantly increase the signal-to-noise ratio, we
      averaged the successively acquired scans during this time. Polystyrene spheres
      dispersed in water at low concentrations were used to test the system. The
      scattering patterns obtained were found to be in good agreement with Mie theory
      calculations.

PMID- 16607990
TI  - Dynamic light scattering by using self-mixing interferometry with a laser diode.
AB  - The power spectrum of the laser intensity is studied when optical feedback in a
      laser diode is used as a sensing configuration for dynamic light-scattering
      experiments. We present a theory that relates the power spectrum obtained from
      standard dynamic light-scattering theory to the intensity power spectrum of the
      laser. This theory provides a concise description of this sensing technique, also
      known as self-mixing interferometry, when it is applied to Doppler shift and line
      broadening measurements of the backscattered field.

PMID- 16607991
TI  - Study of a dual-frequency laser interferometer with unique optical subdivision
      techniques.
AB  - A dual-frequency laser interferometer has been developed based on a low
      performance commercial interferometer. An optical resolution of 1.24 nm and a
      nanometer-scale accuracy have been achieved by using unique techniques to obtain
      an optical subdivision factor of 1/8. A method for reducing static positioning
      errors was also shown. The measurement of a free-falling body was performed to
      test the maximum achievable target velocity of the device. The experimental setup
      for measuring the static positioning errors was also given. The new
      interferometer could be widely used in nanometer-scale fabrications and
      measurements.

PMID- 16607992
TI  - In vitro studies toward noninvasive glucose monitoring with optical coherence
      tomography.
AB  - We use optical coherence tomography (OCT) to measure glucose-induced changes in
      Intralipid and in mouse skin samples in vitro. Mouse skin samples are cultured in
      a CO2 incubator before measurements are made with different amounts of added
      glucose concentrations. The results show that the glucose-induced changes in the
      OCT slope value vary between 20% and 52%/30 mM glucose in different mouse skin
      samples. This change is much larger than the change in 2% Intralipid (2.1%/30 mM)
      and in 5% Intralipid (0.86%/30 mM). Hence the results show that OCT has potential
      to monitor glucose-induced changes in tissues in vitro.

PMID- 16607993
TI  - Highly tunable large-core single-mode liquid-crystal photonic bandgap fiber.
AB  - We demonstrate a highly tunable photonic bandgap fiber, which has a large-core
      diameter of 25 microm and an effective mode area of 440 microm2. The tunability
      is achieved by infiltrating the air holes of a photonic crystal fiber with an
      optimized liquid-crystal mixture having a large temperature gradient of the
      refractive indices at room temperature. A bandgap tuning sensitivity of 27
      nm/degrees C is achieved at room temperature. The insertion loss is estimated to
      be less than 0.5 dB and caused mainly by coupling loss between the index-guided
      mode and the bandgap-guided mode.

PMID- 16607994
TI  - Designing light-emitting diode arrays for uniform near-field irradiance.
AB  - We analyze the first-order design of light sources consisting of multiple light
      emitting diodes (LEDs) to uniformly illuminate a near target plane by considering
      each single LED as an imperfect Lambertian emitter. Simple approximate equations
      and formulas are derived for the optimum LED-to-LED spacing, i.e., the optimum
      packaging density, of several array configurations to achieve uniform near-field
      irradiance.

PMID- 16607995
TI  - One-dimensional spatial dark soliton-induced channel waveguides in lithium
      niobate crystal.
AB  - The anisotropic dependence of the formation of one-dimensional (1-D) spatial dark
      solitons on the orientation of intensity gradients in lithium niobate crystal is
      numerically specified. Based on this, we propose an approach to fabricate channel
      waveguides by employing 1-D spatial dark solitons. By exposure of two 1-D dark
      solitons with different orientations, channel waveguides can be created. The
      structures of the channel waveguides can be tuned by adjustment of the widths of
      the solitons and/or the angles between the two exposures. A square channel
      waveguide is experimentally demonstrated in an iron-doped lithium niobate crystal
      by exposure of two orthogonal 1-D dark solitons in sequence.

PMID- 16607996
TI  - Lattice design for subaperture stitching test of a concave paraboloid surface.
AB  - Lattice design is subtle and complicated for the subaperture stitching test of
      aspheric surfaces. Methods are described in this paper for the collection and
      arrangement of subapertures, and calculation of the best-fit sphere for each
      subaperture. The best-fit sphere is determined by minimizing the mean-square
      aspheric deviations in the form of a surface integral. Finally, a numerical
      example is given to illustrate the procedure, and also to verify the validity of
      our proposed methods.

PMID- 16607997
TI  - Contrast enhancement for electronic speckle pattern interferometry fringes by the
      differential equation enhancement method.
AB  - Electronic speckle pattern interferometry fringe patterns usually have poor
      contrast so it is important to enhance fringe contrast for the extraction of
      phase from a single fringe pattern. We present new enhancement methods based on
      differential equations (called DE enhancement methods) to electronic speckle
      pattern interferometry fringes. The DE enhancement methods transform the image
      processing to solve differential equations. With the proposed methods, the
      visibility of the correlation speckle fringe patterns can be improved
      significantly. We tested the proposed methods on computer-simulated speckle
      correlation fringes and experimentally obtained fringes, and we compared the new
      method with other contrast enhancement techniques. The experimental results
      illustrate the performance of this approach.

PMID- 16607998
TI  - Particle extinction measured at ambient conditions with differential optical
      absorption spectroscopy. 2. Closure study.
AB  - Spectral particle extinction coefficients of atmospheric aerosols were measured
      with, to the best of our knowledge, a newly designed differential optical
      absorption spectroscopy (DOAS) instrument. A closure study was carried out on the
      basis of optical and microphysical aerosol properties obtained from nephelometer,
      particle soot/absorption photometer, hygroscopic tandem differential mobility
      analyzer, twin differential mobility particle sizer, aerodynamic particle sizer,
      and Berner impactors. The data were collected at the urban site of Leipzig during
      a period of 10 days in March 2000. The performance test also includes a
      comparison of the optical properties measured with DOAS to particle optical
      properties calculated with a Mie-scattering code. The computations take into
      account dry and ambient particle conditions. Under dry particle conditions the
      linear regression and the correlation coefficient for particle extinction are
      0.95 and 0.90, respectively. At ambient conditions these parameters are 0.89 and
      0.97, respectively. An inversion algorithm was used to retrieve microphysical
      particle properties from the extinction coefficients measured with DOAS. We found
      excellent agreement within the retrieval uncertainties.

PMID- 16607999
TI  - Narrow-linewidth, tunable ultraviolet, Ti:sapphire laser for environmental
      sensing.
AB  - We describe a compact, narrow-linewidth, etalon-tuned titanium:sapphire laser
      cavity that is designed for field environmental sensing and is pumped by the
      second harmonic of a kilohertz Nd:YAG laser. The fundamental tunable range is
      from 690 to 1100 nm, depending on mirror reflectivities and the optics kit used.
      The conversion efficiency is at least 25% for the fundamental and 2-3% for
      intracavity frequency doubling from 3.5 to 4 W 532 nm pump power. The linewidth
      is <0.1 cm(-1), and the pulse width is 18 ns. Applications of this cavity include
      the measurement of trace gas species by laser-induced fluorescence, cavity
      ringdown spectroscopy, and micropulse lidar in the UV-visible regions.

PMID- 16608000
TI  - Apparent and inherent optical properties of turbid estuarine waters:
      measurements, empirical quantification relationships, and modeling.
AB  - Spectral measurements of remote-sensing reflectance (Rrs) and absorption
      coefficients carried out in three European estuaries (Gironde and Loire in
      France, Tamar in the UK) are presented and analyzed. Typical Rrs and absorption
      spectra are compared with typical values measured in coastal waters. The
      respective contributions of the water constituents, i.e., suspended sediments,
      colored dissolved organic matter, and phytoplankton (characterized by chlorophyll
      a), are determined. The Rrs spectra are then reproduced with an optical model
      from the measured absorption coefficients and fitted backscattering coefficients.
      From Rrs ratios, empirical quantification relationships are established,
      reproduced, and explained from theoretical calculations. These quantification
      relationships were established from numerous field measurements and a reflectance
      model integrating the mean values of the water constituents' inherent optical
      properties. The model's sensitivity to the biogeochemical constituents and to
      their nature and composition is assessed.

PMID- 16608001
TI  - Electro-optic Q switch of an La3Ga5SiO14 crystal.
AB  - We study the influence of the electro-optic and optical activity effects of a
      crystal on the arbitrary linearly polarized light propagating along the optical
      axis and design an experiment to demonstrate this. According to the theory and
      the experimental results, we achieve a successful voltage-decreased electro-optic
      Q switch of the La3Ga5SiO14 crystal.

PMID- 16608002
TI  - Inversion of irradiance and remote sensing reflectance in shallow water between
      400 and 800 nm for calculations of water and bottom properties.
AB  - What we believe to be a new inversion procedure for multi- and hyperspectral data
      in shallow water, represented by the subsurface irradiance and remote sensing
      reflectance spectra, was developed based on analytical equations by using the
      method of nonlinear curve fitting. The iteration starts using an automatic
      determination of the initial values of the fit parameters: concentration of
      phytoplankton and suspended matter, absorption of gelbstoff, bottom depth, and
      the fractions of up to six bottom types. Initial values of the bottom depth and
      suspended matter concentration are estimated analytically. Phytoplankton
      concentration and gelbstoff absorption are initially calculated by the method of
      nested intervals. A sensitivity analysis was made to estimate the accuracy of the
      entire inversion procedure including model error, error propagation, and
      influence of instrument characteristics such as noise, and radiometric and
      spectral resolution. The entire inversion technique is included in a public
      domain software (WASI) to provide a fast and user-friendly tool of forward and
      inverse modeling.

PMID- 16608003
TI  - Beam attenuation coefficient retrieval by inversion of airborne lidar-induced
      chromophoric dissolved organic matter fluorescence. I. Theory.
AB  - It is shown that the oceanic beam attenuation coefficient can be retrieved from
      airborne laser-induced and depth-resolved chromophoric dissolved organic matter
      (CDOM) fluorescence. The radiative transfer equation (RTE) retrieval methodology
      does not require a laser beam spread function model since two CDOM fluorescence
      bands are used in conjunction with a beam attenuation spectral model, is self
      normalizing since the CDOM absorption coefficient and laser beam irradiance are
      common to both fluorescence observational channels, and is enabled by the known
      isotropic phase function for CDOM fluorescence. Although this RTE analytical
      inversion theory is exact, the retrieval uncertainty is reduced by configuring
      the proposed lidar in the multiple-field-of-view beam attenuation mode to
      significantly diminish observation of multiple scattering. The theory can be
      applied over wide regions of the ocean's continental margins, estuaries, lakes,
      and rivers that are known to have sufficient CDOM.

PMID- 16608004
TI  - Tropospheric ozone profiles from a ground-based ultraviolet spectrometer: a new
      retrieval method.
AB  - We present, to the best of our knowledge, a new method to retrieve tropospheric
      ozone (O3) profiles from ground-based ultraviolet spectroscopic measurements.
      This method utilizes radiance spectra in the Huggins bands (i.e., 300-340 nm)
      measured at three off-axis angles (e.g., 45 degrees, 75 degrees, and 85 degrees)
      normalized to direct-Sun irradiances or zenith-sky radiances with the total
      column O3 derived from direct-Sun or zenith-sky measurements as a constraint. The
      vertical resolution of the retrieved O3 values ranges from approximately 3 km
      near the surface to approximately 12 km at 20 km altitude. This method can be
      used to measure diurnal variation of tropospheric O3 profiles and is
      complementary to the Umkehr method that mainly measures ozone profiles in the
      stratosphere.

PMID- 16608006
TI  - [Forecast].

PMID- 16608005
TI  - Spectral calibration of hyperspectral imagery using atmospheric absorption
      features.
AB  - One of the initial steps in the preprocessing of remote sensing data is the
      atmospheric correction of the at-sensor radiance images, i.e., radiances recorded
      at the sensor aperture. Apart from the accuracy in the estimation of the
      concentrations of the main atmospheric species, the retrieved surface reflectance
      is also influenced by the spectral calibration of the sensor, especially in those
      wavelengths mostly affected by gaseous absorptions. In particular, errors in the
      surface reflectance appear when a systematic shift in the nominal channel
      positions occurs. A method to assess the spectral calibration of hyperspectral
      imaging spectrometers from the acquired imagery is presented in this paper. The
      fundamental basis of the method is the calculation of the value of the spectral
      shift that minimizes the error in the estimates of surface reflectance. This is
      performed by an optimization procedure that minimizes the deviation between a
      surface reflectance spectrum and a smoothed one resulting from the application of
      a low-pass filter. A sensitivity analysis was performed using synthetic data
      generated with the MODTRAN4 radiative transfer code for several values of the
      spectral shift and the water vapor column content. The error detected in the
      retrieval is less than +/- 0.2 nm for spectral shifts smaller than 2 nm, and less
      than +/- 1.0 nm for extreme spectral shifts of 5 nm. A low sensitivity to
      uncertainties in the estimation of water vapor content was found, which
      reinforces the robustness of the algorithm. The method was successfully applied
      to data acquired by different hyperspectral sensors.

PMID- 16608007
TI  - [How does success in the 1st cycle of medical school relate to outcome in the 3rd
      doctorate? Behavior of 1st generation students at the Brussels Free University
      under the numerus clausus].
AB  - The aim of our work was to use the results of the 1st cycle of study in medical
      school to explore success in 3rd doctorate students in two cohorts (n = 82) of
      1st generation students in the numerus clausus system. Because of the homogeneity
      of mean percentages in the two cohorts and the nil cohort effect on the evolution
      of performance across study years, the two samples were combined for further
      analyses. While success (end-of-year percentage) in each of the 3 years of the
      1st cycle was positively correlated to success in the other two, the positions
      (according to ranks) of the students in their group only weakly coincided, if at
      all, between the 1st cycle and the 3d doctorate. The analysis of correlations
      between percentages in the 4 years (3 years in the 1st cycle and 3d doctorate)
      showed that 25% of the variance in the 3d doctorate is shared with outcome in the
      1st year and only 7% with that in the 2d year; outcome in the 3d year of the 1st
      cycle did not contribute at all to outcome in the 3d doctorate. Besides, the
      chance of an excellent success in the 3d doctorate, defined as being among the 10
      best performers, was positively associated to the end-of-year percentage in the
      1st year, while neither 2d year nor 3d year results contributed to the
      prediction, as the logistic regression analysis demonstrated. These results, with
      a significant contribution of the 1st study year outcome to the success in the 3d
      doctorate of medical school, were obtained in the context of the numerus clausus
      and contrast with those obtained in a study preceding this selective procedure,
      and showing instead the 3d year of the 1st cycle as more predictive. This result
      could be taken as supporting the very newly established selection process at the
      end of the 1st study year.

PMID- 16608008
TI  - [Diagnosis and treatment of pulmonary embolism].
AB  - Pulmonary embolism (PE) is a common disease that poses a major diagnostic
      challenge because symptoms and signs are neither sensitive nor specific. However,
      patients with suspected PE can be classified into low, moderate and high clinical
      probability groups on the basis of symptoms and signs of PE, the presence of risk
      factors and the presence or absence of a likely alternative diagnosis.
      Stratification of patients into groups according to the clinical or pretest
      probability is imperative for proper selection of further diagnostic tests. The
      role of D-dimer testing is limited to the ruling out of PE in patients with low
      or moderate clinical probability. Conversely D-dimer testing is useless in
      patients, with high clinical probability. Chest CT has become an attractive means
      for an accurate diagnosis of PE and may replace lung scanning as first-line
      imaging test in particular in patients with underlying pulmonary disease or
      abnormal chest radiograph. Initial treatment for patients with non massive PE
      consists of therapeutic anti-coagulation with low molecular weight heparin (LMWH)
      and early overlapping with oral anticoagulants. In patients with active cancer,
      long-term treatment with LMWH is recommended. Duration of anticoagulant treatment
      is based on the balance between the risk of recurrent venous thromboembolism
      (depending mainly on the reversibility of risk factor, the presence of cancer,
      thrombophilia or previous venous thromboembolic episodes) and the risk of
      bleeding.

PMID- 16608009
TI  - [Management of resectable non-small cell lung cancer. Guidelines of clinical
      practice made by the European Lung Cancer Working Party].
AB  - The present article reports the guidelines made by the European Lung Cancer
      Working Party (ELCWP) in April 2005 for the management of resectable non-small
      cell lung cancer (NSCLC). They aim to answer to the following eleven questions:
      1) Is surgery the best therapy for a potentially resectable cancer? 2) How is
      complete resection defined? 3) Is a systematic lymph node dissection necessary
      during surgery? 4) Which place for radiotherapy after complete resection? 5)
      Should adjuvant or neoadjuvant chemotherapy be administered in case of clinical
      stage I or II? 6) Should adjuvant chemotherapy be administered in case of
      pathological stage I or II? 7) Is adjuvant therapy advisable after complete
      resection for pathological stage IIIA N2? If yes, what type: chemotherapy,
      radiotherapy, radiochemotherapy? 8) What are the indications for surgery after
      induction treatment in clinical stage IIIA or B? 9) In clinical stage IIIA or B,
      is preoperative induction therapy required, and if yes, what type? 10) What type
      of treatment is indicated after an incomplete surgical resection? 11) What is the
      best regimen for (neo) adjuvant chemotherapy?

PMID- 16608010
TI  - [Cutaneous side effects of a long-term treatment by hydroxyurea].
AB  - Hydroxyurea is an antitumour agent used most commonly to treat myeloproliferative
      disorders. We present a clinical observation illustrating different cutaneous
      side effects susceptible to occur during a long-term treatment by hydroxyurea :
      leg ulceration, oral ulcer and spinocellular carcinoma. This clinical observation
      is completed by a review of the literature published on the cutaneous side
      effects of hydroxyurea treatment.

PMID- 16608011
TI  - [Omega-3 fatty acids and cardiovascular diseases].
AB  - Most--but not all--epidemiological studies have demonstrated that omega-3 intake,
      either from nutrition or supplementation, reduces cardiovascular risk. A few
      intervention studies have shown a reduction of studden death in patients followed
      after a myocardial infarction. However EBM studies from the Cochrane Library do
      not confirm the real advantage of omega-3 in any group of subjects. Probably, the
      most interesting prescription of omega-3 supplementations would benefit to the
      patients after myocardial infarction, in addition to drugs that have proved their
      efficacy (aspirine, beta-blocker statin and ACE inhibitor).

PMID- 16608012
TI  - [Organization of obstetrical teaching and practice in our regions (particularly
      in Brussels) during the XIXth century (second part)].
AB  - The Napolean defeat at Waterloo entailed drastic changes of health services in
      our regions. Under the new Dutch rule, many different medical grades were put in
      use making the pertinent legal rules very difficult to apply. At Belgian
      independence, the Free University of Brussels was founded including a Faculty of
      Medicine of which the clinical infrastructure was mainly the Saint-Pierre
      Hospital located at the Hal Gate. In 1880, provincial schools for midwives were
      established while operative obstetrics remained in the hands of general surgeons.
      At Brussels, medical students rightly complained about the poor training of
      general practitioners in obstetrics. Until the first third of the XXth century,
      the vast majority of deliveries took place at home under the supervision of a
      midwife. A consultant surgeon was called upon only if deemed indispensable.

PMID- 16608013
TI  - [Development of general medicine].

PMID- 16608014
TI  - Intraoperative three-dimensional fluoroscopic cholangiography.
AB  - Precise intraoperative assessment of the architecture of the biliary tree could
      reduce lesions to intra- or extrahepatic bile ducts. The aim of this study was to
      test feasibility of intraoperative three-dimensional imaging during liver
      resections. Isocentric C-arm fluoroscopy acquires three-dimensional images during
      a 190 degrees orbital rotation. The bile ducts were displayed three-dimensionally
      by realtime rotational projections or multiplanar reconstructions. The technique
      was established ex vivo in a preserved cadaveric human liver. Intraoperative
      three-dimensional cholangiography was performed in five patients with centrally
      located liver malignancies. Complete data acquisition in 3 patients depicted
      precise anatomical details of the architecture of the biliary tree up to third
      order divisions. Biliary imaging can be improved by the application of real-time
      intraoperative three-dimensional cholangiography. For the development of computer
      aided navigation in hepatobiliary procedures, this technique could be an
      important prerequisite for defining landmarks of the liver in a three-dimensional
      space.

PMID- 16608015
TI  - Assessment of the reproducibility of quantitative hepatobiliary scintigraphy
      (QHBS) in patients with sphincter of Oddi dysfunction (SOD)--inappropriate method
      or intermittent disease?
AB  - BACKGROUND/AIMS: Although quantitative hepatobiliary scintigraphy (QHBS) was
      originally suggested as a promising method in the diagnosis of sphincter of Oddi
      dysfunction (SOD), it was recently claimed that QHBS displays poor
      reproducibility and specificity in cholecystectomized patients. The aim of the
      present study was to assess the reproducibility of QHBS in cholecystectomized
      patients. METHODOLOGY: 28 cholecystectomized patients with suspected SOD
      underwent QHBS evaluation on two separate occasions. On the basis of the clinical
      and endoscopic retrograde cholangiopancreatography (ERCP) data, patients with
      suspected SOD were categorized by applying the Geenen and Hogan classification:
      10 were identified as having SOD of biliary type I (SO stenosis group), and the
      remaining 18 patients as having SOD of biliary type II or III (SO dyskinesia
      group). During the same period, 12 asymptomatic cholecystectomized individuals
      (control group) were recruited to undergo QHBS evaluation on two separate
      occasions. QHBS was performed with our standard method in all subjects. After an
      overnight fast, 140MBq 99mTc-EHIDA was injected intravenously. Digital images
      were recorded continuously on a 128 x 128 matrix, at one frame/min for 90 min.
      For the final analysis, the liver-choledochus T. difference (LCTD), half-time of
      excretion of the common bile duct (CBD T1/2), and the duodenum appearance time
      (DAT) were applied. RESULTS: In the 12 asymptomatic controls, the QHBS parameters
      were highly reproducible, all but 6 of the 72 separate parameters obtained from
      two repeated studies were within our normal limits. In all 10 patients belonging
      in the SO stenosis group, the QHBS parameters were markedly abnormal and again
      highly reproducible. All of the 60 separate quantitative parameters obtained in
      this group from the two repeated studies were high above our normal range. In
      contrast, in the 18 patients with SO dyskinesia, the QHBS parameters were
      distinctly variable and poorly reproducible. Of the 108 separate quantitative
      parameters obtained in this group the two separate studies, 55 were normal and 53
      were above our normal range. Of the 18 SO dyskinesia patients, only 9 had at
      least one quantitative parameter abnormal in both QHBS examinations. CONCLUSIONS:
      QHBS is a highly reproducible technique in cholecystectomized controls and in
      patients with SO stenosis. In contrast, the reproducibility of QHBS is poor in
      patients with SO dyskinesia, which is probably a consequence of the disease
      characteristics rather than methodological insufficiency of QHBS.

PMID- 16608016
TI  - The role of endoscopic treatment in postoperative bile leaks.
AB  - BACKGROUND/AIMS: Bile leak is among the most common and serious complications of
      biliary tract surgery. The aim of this non-randomized study was to evaluate the
      role of endoscopic intervention as an accepted treatment for this complication.
      METHODOLOGY: An endoscopic retrograde cholangiopancreatography (ERCP) database
      was reviewed retrospectively to identify all cases of bile leak related to
      cholecystectomy (laparoscopic or open). Patients' records and endoscopy reports
      were reviewed. Moreover, structured telephone interviews were conducted to
      collect data. RESULTS: Twenty-four patients, 4 males and 20 females, with a
      median age of 54 (range 28-76 years) with suspected postcholecystectomy bile
      leaks were referred for ERCP performed 3-73 days after operation (mean 9.5 days).
      All but one case had high-grade bile-like liquid outflowing from the original
      drainage tubes or the fistulous tract of T-tube. One patient presented with
      bilious ascites, 17 patients had sudden or gradual abdominal pain, 3 jaundice, 2
      abdominal pain with fever, and 1 nausea and vomiting. ERCP was successful in all
      cases, and revealed leakage from the cystic stump in 10 cases, from a common bile
      duct (CBD) defect in 6, from a common hepatic duct defect in 3, from the
      gallbladder bed in 2, from a T-tube track in 1, and complete CBD transection in 2
      patients. Seventeen patients were successfully treated by endoscopic
      sphincterotomy (ES) plus endoprosthesis, 3 by stent placement without
      sphincterotomy, 2 with complete transection by proximal hepaticojejunostomy, and
      2 patients with leakage from the cystic stump and a CBD defect were operated
      after unsuccessful endoscopic intervention. CONCLUSIONS: ERCP is recommended as a
      safe and efficacious intervention to detect and treat postoperative bile leaks.
      ES plus endoprosthesis is effective for the treatment of bile leakage. Endoscopic
      stenting without sphincterotomy may be offered as a primary option in young
      patients with postoperative bile leaks.

PMID- 16608017
TI  - Clinical usefulness of the angiotensin II receptor antagonist losartan in
      patients with portal hypertensive gastropathy.
AB  - BACKGROUND/AIMS: An elevated portal vein pressure is an important factor in the
      onset of portal hypertensive gastropathy associated with liver cirrhosis, and
      propranolol or vasopressin (drugs with a portal hypotensive effect) are used to
      treat this problem. It has been reported that angiotensin II receptor
      antagonists, which were developed as antihypertensive agents, also have a portal
      hypotensive effect, but their usefulness for portal hypertensive gastropathy is
      unclear. In this study, the angiotensin II receptor antagonist losartan was
      administered to 16 portal hypertensive gastropathy patients, and its clinical
      usefulness was examined. METHODOLOGY: Losartan was administered once a day after
      breakfast at a dose of 25mg or 50mg. The effect on portal hypertensive
      gastropathy was evaluated from the endoscopic findings at baseline and after 4
      weeks of administration. And changes of portal hemodynamics were monitored by
      pulse Doppler ultrasonography at baseline and after 4 weeks of administration.
      RESULTS: Portal hypertensive gastropathy was found to have improved in nine out
      of 16 patients for an efficacy rate of 56%. The efficacy rate in the 50mg group
      (n=6) was 83%, and was higher than the rate of 40% in the 25mg group (n = 10).
      The mean portal vein blood flow velocity was found to increase significantly,
      while the congestion index decreased significantly, supporting evidence of a
      decrease in portal pressure. CONCLUSIONS: Losartan may become one of the
      effective treatments for portal hypertensive gastropathy in the future.

PMID- 16608018
TI  - Monitoring and evaluation of intraperitoneal bleeding (IPB) by small portable
      ultrasonography during transcatheter arterial embolization (TAE) in abdominal
      pelvic trauma patients with shock: as a monitor for early detection of increase
      of IPB.
AB  - BACKGROUND/AIMS: Blunt abdominal-pelvic trauma patients with shock often require
      transcatheter arterial embolization (TAE), and may also require surgery if
      intraperitoneal bleeding (IPB) becomes massive. Deciding whether the patient
      should undergo surgery is highly critical. We sometimes perform TAE without
      attention to IPB because it has been difficult to evaluate the volume of IPB
      exactly during TAE. Currently we use small portable ultrasonography (PUS) as a
      monitor of volume of IPB during TAE. The aim of this study is to clarify the
      usefulness of PUS for monitoring changes in IPB during TAE. METHODOLOGY: We
      examined the volume of IPB by PUS during TAE without disturbing the operators of
      TAE. In our protocol, if the volume of IPB showed rapid increase we tried to
      perform a surgical procedure. The design of this study was a prospective case
      series study. RESULTS: We examined 26 patients. Increase of IPB was detected in 3
      cases; two were undergoing angiography for ileac and renal arteries when PUS
      indicated increase of IPB, which drew attention to their hepatic arteries. The
      other was examined initially for internal ileac artery and underwent surgery
      because of an increase of IPB. In the other 22 cases, we confirmed no increment
      of IPB by PUS and continued the procedure. CONCLUSIONS: PUS is useful for
      deciding the order of therapeutic procedure, and is a useful monitoring
      instrument for increase of IPB.

PMID- 16608019
TI  - Impact of the two-layer method on the quality of isolated pancreatic islets.
AB  - BACKGROUND/AIMS: We have already reported that the two-layer method (UW/PFC)
      reduces warm and cold ischemic injuries before islet isolation, and results in
      improvement of islet yield and viability. In this study, we try to evaluate the
      effect of the two-layer method on isolated islets. METHODOLOGY: We used male
      Wister rats. Isolated islets were cultured or preserved in various conditions for
      24 hours. In group 1, islets were not cultured (control). In group 2, islets were
      cultured in RPMI at 37 degrees C. In groups 3 and 4, islets were cultured with
      "modified" two-layer method (RPMI/PFC) at 37 degrees C and 4 degrees C,
      respectively. In groups 5 and 6, islets were preserved in UW and with the two
      layer method (UW/PFC), respectively at 4 degrees C. Islets in each group were
      evaluated in terms of function and viability in vitro. RESULTS: Stimulation
      Indices were 1.3, 2.6, 3.7, 1.2, 1.4, and 2.4 in groups 1, 2, 3, 4, 5 and 6,
      respectively. Islets in groups 2, 3 and 6 showed clear response to glucose
      stimulation. Among these 3 groups, the total viability of islets assessed by
      FDA/PI staining was 88%, 92%, and 76% in groups 2, 3, 6, respectively.
      CONCLUSIONS: Although in vivo studies are mandatory, the present study is
      supportive that the "modified" two-layer method (RPMI/PFC), which uses oxygenated
      PFC and RPMI, may be superior to conventional culture method with RPMI. This
      method may achieve further improvement of islet viability before implantation.

PMID- 16608020
TI  - Clinical outcomes of metallic stent insertion for obstructive colorectal cancer.
AB  - BACKGROUND/AIMS: As the treatment of acute malignant obstruction of the left
      colon, self-expandable metallic stent insertion has been clinically used with
      good results. The aim of this study is to analyze the outcome of planned
      operation after stent insertion for obstructive colorectal cancer. METHODOLOGY:
      From 2000 to 2003, among 37 patients treated for obstructive colorectal cancer,
      we compared hospital days and complications between Group A (n=18) and Group B
      (n=19). Group A included the patients who underwent planned operation after stent
      insertion and Group B included the patients who underwent planned operation after
      emergency temporary colostomy formation. RESULTS: In Group A, complications after
      stent insertion were perforation with abscess formation (n=1) and stent migration
      (n=2). Complications after definitive operation were not observed. In Group B,
      complications after temporary colostomy involed stoma site wound infection (n=2).
      Complications after definitive surgery were as follows: anastomotic leakage
      (n=1), pneumonia with acute renal failure (n= 1), wound infection (n=2). In group
      A and group B, hospital day after decompressive procedure was 5+/-4.0 days
      (range, 1-16 days) vs. 14+/-4.7 days (range, 7-27 days) (P=0.000). Hospital day
      after definitive operation was 11+/-4.0 days (range 8-22 days) vs. 16+/-9.2 days
      (range 10-41 days) (P=0.002). CONCLUSIONS: Because preoperative self-expandable
      metallic stent insertion for obstructive colorectal cancer had better
      postoperative results and shorter hospital days than emergent diverting
      colostomy, this procedure is a good "bridge to surgery".

PMID- 16608021
TI  - Telomerase subunit immunoreactivity and recurrence in colorectal cancer.
AB  - BACKGROUND/AIMS: Telomerase is expressed in human germ tissues and in the
      majority of primary human tumors. The catalytic subunit of telomerase, hTERT is
      one of the most important components of telomerase. In this study we attempted to
      show by means of immunohistochemistry the association between hTERT expression
      and recurrence in 128 colorectal cancer patients surgically treated in the
      University of Tokyo Hospital. METHODOLOGY: Immunostaining was performed in a
      conventional manner using a commercial monoclonal antibody. RESULTS: In our
      results, negative TERT immunoreactivity in the primary lesion was significantly
      associated with advanced tumor stage (p=0.0007), the presence of lymph node
      metastasis (p=0.00018) and recurrence (p<0.0001). Recurrence-free survival rate
      was significantly lower in patients with negative TERT immunoreactivity
      (p=0.0002). In the same way, if limited in patients without metastatic lymph
      nodes at surgery or in patients with T3 or T4 tumor, the recurrence-free survival
      rate was significantly lower in those with negative TERT immunoreactivity
      (p=0.019, p=0.016). CONCLUSIONS: Negative TERT immunoreactivity may be a novel
      indicator for poor prognosis of colorectal cancer patients and additional studies
      with a larger number of patients may lead to identifying patients at high risk
      for recurrence more accurately.

PMID- 16608022
TI  - Fish detected p53 deletion and N-MYC amplification in colorectal cancer.
AB  - BACKGROUND/AIMS: Data about p53 condition in sporadic colorectal cancer and its
      impact on clinical features is controversial, and studies regarding N-myc gene in
      colorectal cancer are limited in number. Our aim was to determine the frequency
      of p53 deletion and N-myc amplification by fluorescence in situ hybridization
      method in colorectal cancer and their relationship with clinical parameters.
      METHODOLOGY: The study was prospectively derived from 40 patients who were
      diagnosed as having colorectal cancer (Dukes' stages: 11 B, 18 C, 11 D) and went
      to surgery. Fresh tumor samples from all patients and adjacent normal tissue from
      16 patients as control specimens were obtained. Locus specific fluorescence in
      situ hybridization probes was used for p53 and N-myc gene. For each sample,
      hundred interphase nuclei were analyzed based on their fluorescence phenotype.
      RESULTS: Both p53 allelic loss and N-myc amplification were found in 21 cancer
      tissues, while p53 allelic loss was not observed in any of control tissue, and N
      myc amplification only in 1 (p<0.001, p<0.01). Mutations were significantly
      related with metastasis. CONCLUSIONS: Our study indicates that p53 and N-myc
      mutations are frequently found in tumor tissue of colorectal cancer and both gene
      alterations are correlated with the more aggressive tumor phenotype.

PMID- 16608023
TI  - Second-line combination chemotherapy of oral S-1 with cisplatin and irinotecan
      for colorectal cancer resistant to 5-FU.
AB  - BACKGROUND/AIMS: A phase I clinical trial has been planned to determine the
      recommended dose and to assess the safety and efficacy of combination
      chemotherapy of S-1 with cisplatin and irinotecan (SCI regimen) as a second-line
      treatment in 5-fluorouracil (5-FU) resistant colorectal cancer (CRC).
      METHODOLOGY: Patients with unresectable recurrent or metastatic CRC were enrolled
      in this study for second-line treatment. On an outpatient basis, the patients
      received a treatment SCI regimen comprising S-1 oral administration for 28 days
      followed by withdrawal for 2 weeks, plus cisplatin and irinotecan were
      administered on days 1, 8, 15 and 22 by intravenous injection. These courses were
      repeated every 6 weeks. Starting doses were 70 mg/m2 S-1, 6 mg/m2 Cisplatin, and
      60 mg/m2 Irinotecan. RESULTS: A total of 29 patients was enrolled. Dose-limiting
      toxicities were fatigue, nausea, and leucopenia. Twenty-three patients at
      recommended dose were evaluable for treatment response. The response rate was
      21.7% (5 partial responses, 13 stable diseases, and 5 progressive diseases). The
      median progression-free survival rate was 4.3 months; the median survival time
      was 9.6 months. CONCLUSIONS: The SCI regimen is feasible in an outpatient setting
      and should be considered as second-line chemotherapy for patients with 5-FU
      resistant CRC.

PMID- 16608024
TI  - A phase I trial of CPT-11 in combination with 5-fluorouracil plus leucovorin
      chemotherapy for patients with metastatic colorectal cancer.
AB  - BACKGROUND/AIMS: To establish a safe and practical chemotherapeutic regimen using
      CPT-11 in combination with 5-FU plus leucovorin (5-FU/LV) for patients with
      metastatic colorectal cancer in an outpatient setting, a phase I clinical trial
      was conducted. METHDOLOGY: Eligible patients received the RPMI regimen of I-LV
      (200 mg/m2, for 2 hours) plus 5-FU (333 mg/m2, bolus) weekly for 4 weeks followed
      by a 2-week rest. CPT-11 was administered over the 5-FU/LV therapy at the 1st and
      3rd week of every treatment cycle before the bolus 5-FU. Dose escalation of CPT
      11 from 25 to 100 mg/m2 was done for every cohort consisting of at least 3
      patients to define a dose-limiting toxicity (DLT), maximal tolerated dose (MTD),
      and recommended dose (RD) for a phase II trial. RESULTS: Twenty-one patients with
      metastatic colorectal cancer were enrolled. Hematologic toxicity was very
      infrequently observed. One patient enrolled at level 1 (25 mg/m2 CPT-11), but not
      the other patients, had muscle weakness at grade 3 and needed to be hospitalized.
      Hair loss at grade 1 was observed in 3 of 21 patients. Gastrointestinal toxicity,
      including nausea, was commonly observed throughout the dose levels. Diarrhea was
      frequently observed at doses higher than level 4 (60 mg/m2 CPT-11), and 2 of the
      3 patients at dose level 6 (100 mg/m2 CPT-11) experienced diarrhea at grade 3 and
      needed to be hospitalized. As for the overall tumor responses, 3 partial
      responses (PR), 10 stable diseases, and 6 progressive diseases were observed,
      with 2 of the PRs occurring at dose level 5 (80 mg/m2 CPT-11). CONCLUSIONS: These
      results suggest that our treatment regimen using CPT-11 in combination with 5
      FU/LV is a safe regimen in an outpatient setting and effective for patients with
      metastatic colorectal cancer. The DLT is diarrhea at the MTD of 100 mg/m2 of CPT
      11, and 80 mg/m2 CPT-11 is recommended for the next phase II trial.

PMID- 16608025
TI  - Gum-chewing stimulates bowel motility after surgery for colorectal cancer.
AB  - BACKGROUND/AIMS: During the perioperative period after open colorectal surgery,
      surgical stress affects changes in the autonomic nervous system of patients. The
      decreased intestinal motility results in many complaints for patients. To resolve
      this problem, the usefulness of gum-chewing for improving the motility was
      examined. METHODOLOGY: Twenty-two patients with colorectal cancer were divided
      into two groups; gum-chewing and control groups. From after their operation,
      chewing gum was given to the former group three times a day. RESULTS: The first
      passage of flatus and stool in the chewing-gum group after operation were 35 and
      50 hours, respectively, sooner for the controls. CONCLUSIONS: It was concluded
      that gum-chewing provides a simple and effective method to improve the
      postoperative state of patients.

PMID- 16608026
TI  - Oral regimen consisting of UFT/UZEL for elderly patients with colorectal cancer.
AB  - BACKGROUND/AIMS: A clinical trial has been planned to assess the safety and
      efficacy of oral administration of UFT and leucovorin (UZEL) in elderly patients
      with advanced colorectal cancer (CRC). METHODOLOGY: Twenty-six patients with
      advanced CRC who were over 70 years and considered ineligible for combination
      chemotherapy received oral UFT 300 mg/day and UZEL 75mg/day were administered
      orally for 28 days followed by a 7-day rest period. Treatment was repeated every
      5 weeks until disease progression. RESULTS: A total of 106 cycles of UFT/UZEL
      were administered (median, four cycles; range, one to twelve cycles). UFT/UZEL
      was well tolerated. The response rate was 11% (3 partial responses, 16 stable
      diseases, and 7 progressive diseases). The median progression-free survival rate
      was 3.9 months and the median survival time was 9.8 months. Treatment-related
      grade 3 and 4 adverse events were not observed. CONCLUSIONS: Oral regimen
      consisting of UFT/ UZEL is effective and well tolerated in elderly patients with
      advanced CRC who are considered ineligible for combination chemotherapy.

PMID- 16608027
TI  - Rectal procidentia treatment by perineal rectosigmoidectomy combined with levator
      ani repair.
AB  - BACKGROUND/AIMS: Perineal rectosigmoidectomy has gained acceptance as a valid
      alternative to treat rectal procidentia with the advantage of decreased surgical
      risk, shorter recovery time, and lower complication rates when compared to
      abdominal approaches, although controversies still exist about its recurrence
      rates and functional results. This study aimed to evaluate the results of
      perineal rectosigmoidectomy combined with repair of the levator ani muscles to
      treat rectal procidentia. METHODOLOGY: Forty-four patients who underwent perineal
      rectosigmoidectomy with levatorplasty for rectal procidentia between 1985 and
      2000 were retrospectively analyzed. RESULTS: There were 41 women and 3 men with
      mean age of 76 (57 to 96) years. Mean duration of symptoms was 29.2 (1 to 40)
      months. Mean length of prolapsed rectum was 8.3cm and the average size of the
      resected segment was 21.2cm. The complication rate was 9.1% and there was no
      mortality associated with this procedure. Mean hospital stay was 3.9 days. During
      a minimum period of follow-up of 24 months (24-120) with a mean of 49 months, the
      recurrence rate was 7.1% (two patients presented recurrence of procidentia and
      another prolapse of the rectal mucosa). Anal continence improved in 36 (85.7%)
      patients. CONCLUSIONS: Perineal rectosigmoidectomy combined with levatorplasty is
      a safe procedure associated with a relatively low morbidity rate, satisfactory
      functional results, and an acceptably low recurrence rate.

PMID- 16608028
TI  - Relationship between bolus transit and LES-relaxation studied with concurrent
      impedance and manometry.
AB  - BACKGROUND/AIMS: Neuromuscular mechanisms regulating esophageal bolus transport
      are well studied. However, detailed data about the relationship between bolus
      transit and lower esophageal sphincter (LES)-relaxation during conventional
      motility testing are still lacking. METHODOLOGY: We performed systematic studies
      in 25 normal subjects, employing a catheter that integrates the two techniques
      impedancometry and manometry in a single instrument for simultaneous recording
      and analysis of the relationship between bolus transit and LES relaxation after
      swallowing saline or yogurt. RESULTS: 195 swallows were analyzed. LES relaxation
      occurred frequently later than UES relaxation. The mean latency between bolus
      entry into the esophagus and LES relaxation was 3.6 +0.2 sec. Two types of
      swallow-induced LES relaxation were observed: (a) LES relaxation preceding bolus
      transit (46 cases or 24%) and (b) LES relaxation occurring during bolus transit
      (149 cases or 76%). In the later case, during 114 (76%) cases of this
      deglutition, the position of the bolus was very close to the LES. CONCLUSIONS:
      During deglutition, LES relaxation seems to be modulated by bolus transit and
      occurs predominantly upon arrival of the bolus in the distal esophagus.

PMID- 16608029
TI  - Efficacy of endoscopic clipping and long-term follow-up of bleeding Dieulafoy's
      lesions in the upper gastrointestinal tract.
AB  - BACKGROUND/AIMS: Dieulafoy's lesion is a rare cause of upper gastrointestinal
      hemorrhage. The aim of this prospective study was to assess the efficacy and
      safety of endoscopic clipping for upper gastrointestinal bleeding due to
      Dieulafoy's lesion. METHODOLOGY: From January 1998 to March 2001, 21 patients (9
      women and 12 men; mean age 66 +/- 16 yrs) with bleeding Dieulafoy's lesion have
      been admitted. Endoscopic clipping was performed in all patients using a clipping
      device consisting of a clip applicator device and stainless steel hemoclips
      (Olympus, Japan). A follow-up endoscopy was performed within the following 24-48
      hours to confirm the success of hemostasis. Hemostatic rate, rebleeding rate,
      amount of blood transfusion, and duration of hospital stay were analyzed.
      RESULTS: The initial hemoclip therapy was successful in 20 out of 21 (95.2%)
      patients. Two patients had recurrent bleeding. One patient in whom recurrent
      bleeding occurred died. The successful surgical treatment was done in one patient
      in whom initial hemoclip therapy was unsuccessful. Therefore, the overall
      hemostasis was observed in 19 out of 21 patients (90.5%). There were no
      complications related to endoscopic therapy. CONCLUSIONS: Endoscopic hemoclipping
      provided a very effective and safe modality for hemostasis in patients with
      bleeding Dieulafoy's lesions.

PMID- 16608030
TI  - Postoperative metabolic and circulatory responses in patients that express SIRS
      after major digestive surgery.
AB  - BACKGROUND/AIMS: Systemic inflammatory response syndrome (SIRS) includes a number
      of pathologic states because of its loose definition. This study assessed
      differences in metabolic and circulatory host responses in various patients with
      SIRS perioperatively. METHODOLOGY: Fifty-four patients who underwent abdominal
      surgeries [gastric resection (n=20), colorectal resection (n=24), hepatic
      resection (n=8)] were divided into two groups: Group A; SIRS (+) on 1
      postoperative day (POD), (n=29), B; SIRS (-) on 1 POD, (n=25). The other eight
      non-operated patients with SIRS caused by infection were enrolled in Group C, as
      common SIRS. Indirect calorimetry, body impedance measurement to assess water
      compartments and pulse dye-densitometry for hemodynamic examination were
      performed in subjects until 14 POD. RESULTS: The ratio of energy expenditure to
      basal energy expenditure (%REE) was significantly increased postoperatively, and
      there were significant differences on %REE from 3 POD to 14 POD between groups A
      and B. However, %REE in group C was 162+/-23%, which was significantly increased
      compared with that at 1 POD of groups A (130 +/- 17%) and B (125+/-18%). Cardiac
      output in group A showed a significant increase until 3 POD compared with that in
      group B but was significantly lower than that in group C. CONCLUSIONS: Subjects
      with common SIRS caused by infection were significantly more hypermetabolic than
      subjects with postoperative SIRS. Adequate energy intake and circulatory
      management should be cautiously determined according to the severity of SIRS.

PMID- 16608031
TI  - Bacterial infections after intestine and multivisceral transplantation. The
      experience of the University of Miami (1994-2001).
AB  - BACKGROUND/AIMS: Bacterial infections (BI) are frequent after intestinal
      transplantation (ITx). Bacteremia, intraabdominal and respiratory infections are
      the leading forms. The objective of this study is to analyze the occurrence,
      determinants and outcome of BI. METHODOLOGY: One hundred and twenty-four patients
      with ITx (39 isolated, 33 liver-intestine, 63 multivisceral). Only major BI were
      considered, including bacteremia, pneumonia, intraabdominal infections, severe
      wound infections. RESULTS: BI occurred in 92.7% of patients during follow-up,
      with an average of 2.9 episodes per patient. Bacteremia was the commonest picture
      (1.7 per patient). More than 80% of patients had a BI before the end of the
      second month. Multivariate analysis showed that the presence of BI was higher
      during the first 2 months after Itx in patients hospitalized before Tx [p=0.029,
      odds ratio (OR) 5.4] and during months 3 to 6 in those treated with Zenapax
      (p=0.003, OR 6.2). Occurrence of BI was increased with mycophenolate mofetil
      treatment (p=0.045 OR 4.2). Intraabdominal infection was more frequent when reTx
      was needed (p=0.0178 OR 15.2), admission before Tx (p=0.034 OR 2.7), IS with MMF
      (p=0.004 OR 6.2) and Zenapax (p=0.026 OR 3.6). BI was the direct cause of death
      in 17.8% of patients, and it was present in 76.2% of patients that died. An
      infectious episode during the first month, a clinically manifested abdominal
      infection and a positive intraabdominal culture were determinants of shorter
      patient survival. CONCLUSIONS: BI continue to be a frequent and dreadful
      complication after ITx. Pretransplant patient condition, IS used and
      postoperative complications are crucial on BI onset and outcome.

PMID- 16608032
TI  - The role of mitogen-activated protein kinases and the participation of intestinal
      congestion in total hepatic ischemia-reperfusion injury.
AB  - BACKGROUND/AIMS: The mitogen-activated protein kinase (MAPK) pathways are
      comprised of key regulatory proteins that control the cellular responses to both
      proliferation and stress signals. This study was performed to examine the degree
      of liver damage and MAPK activation induced by ischemia of varying durations, and
      the association between intestinal congestion and liver dysfunction after hepatic
      ischemia-reperfusion injury. METHODOLOGY: Male Sprague-Dawley rats were divided
      into five groups: sham-operated controls (no hepatic ischemia); 15, 30, or 45 min
      of total hepatic ischemia; or 45 min of total hepatic ischemia with a
      portosystemic shunt. Serum levels of aspartate aminotransferase, alanine
      aminotransferase, lactate dehydrogenase, interleukin-1beta and tumor necrosis
      factor-alpha, as well as liver tissue blood flow were measured. Liver was also
      sampled for MAPK analysis and histopathological examination. RESULTS: Total
      hepatic ischemia for over 30 min, with intestinal congestion, caused severe liver
      damage and an inflammatory cytokine response. A portosystemic shunt attenuated
      ischemia-reperfusion injury and inhibited inflammatory cytokine expression.
      Extracellular signal-regulated kinase was markedly phosphorylated in all groups
      other than the sham-operated group. p38 MAPK and c-Jun N-terminal kinase were
      highly phosphorylated in all groups receiving 30 min or more of ischemia.
      CONCLUSIONS: Prolonged warm total hepatic ischemia-reperfusion injury is
      associated with small intestinal congestion; a portosystemic shunt reduces liver
      damage by inhibiting inflammatory cytokine expression. MAPKs are markedly
      phosphorylated after reperfusion.

PMID- 16608033
TI  - Antiviral therapy using lamivudine and thymosin alpha1 for hepatocellular
      carcinoma coexisting with chronic hepatitis B infection.
AB  - BACKGROUND/AIMS: To observe the recurrence and prognosis of patients with
      hepatocellular carcinoma (HCC) coexisting with chronic hepatitis B infection with
      active virus replication after receiving antivirus therapy using lamivudine and
      thymosin alpha1 postoperatively. METHODOLOGY: From Jan. 2000 to Dec. 2002, 33
      patients with HCC coexisting chronic hepatitis B infection with active virus
      replication were prospectively divided into two groups: control group (n= 17)
      received hepatectomy only, treatment group (n= 16) received hepatectomy and
      lamivudine plus thymosin alpha1 therapy postoperatively. The suppression of HBV
      DNA, HBeAg seroconverted rate, recurrent tumor rate and the median survival for
      the two groups were observed and calculated. RESULTS: For the treatment group and
      control group, the one-year HBV-DNA suppression rate was 100% vs. 6% (p=0.0016);
      HBeAg seroconverted rate was 62.5% vs. 5.9% (p=0.0157); The median recurrent time
      was 7.0 vs. 5.0 months (p=0.0052); The median survival period was 10.0 vs. 7.0
      months (p=0.10053), respectively. CONCLUSIONS: Antivirus therapy using lamivudine
      and thymosin alpha1 postoperatively may suppress the HBV reaction, delay the
      recurrent time and prolong the survival for HCC patients coexisting with chronic
      HBV infection with active virus replication.

PMID- 16608034
TI  - Technical refinement preserving segment 4 to donor in extended right hepatectomy.
AB  - BACKGROUND/AIMS: Donor extended right hepatectomy, including the middle hepatic
      vein (MHV) and a part of segment 4 (Sg4), is performed to overcome inadequate
      graft for large adult recipient as resolving congestion of right anterior
      section. However, using this technique remnant donor liver is often too small.
      Here, we introduce a technical Modified extended right hepatectomy (MERH), in
      which the MHV was excavated preserving the entire Sg4 in the donor. METHODOLOGY:
      We compared clinical outcomes between donors using our technique (n=12) that may
      result in Sg4 congestion, and right hepatectomy (RH, n=12) that may not. MERH was
      performed when the remnant donor liver had a volume exceeding 35% and showed no
      steatosis in preoperative imaging study. RESULTS: No donor died, and there were
      no differences in operative time and postoperative recovery between the two
      groups (p>0.05). The regeneration of the remnant liver after MERH and RH were
      similar (160.2% vs. 187.7% at POD 10; 222.2% vs. 230.5% at 4 months) (p>0.05).
      CONCLUSIONS: Our results show that MERH didn't impair recovery or liver
      regeneration in donors, and indicate that MERH will be useful in adult living
      donor liver transplantation.

PMID- 16608035
TI  - Is intraoperative adjuvant therapy effective for satellite lesions in patients
      undergoing reduction surgery for advanced hepatocellular carcinoma?
AB  - BACKGROUND/AIMS: The effectiveness of intraoperative adjuvant therapy for
      satellite lesions of nonresectable hepatocellular carcinoma (HCC) was
      investigated. METHODOLOGY: We randomly assigned 30 eligible patients with
      advanced-stage HCC with multiple intrahepatic lesions who underwent reduction
      hepatectomy in conjunction with either intraoperative adjuvant therapy
      (hepatectomy plus microwave coagulonecrotic therapy or radiofrequency ablation)
      or postoperative adjuvant therapy (transcatheter arterial embolization). The
      cumulative survival rates were obtained for both groups using the Kaplan-Meier
      method and compared using the log-rank test. To evaluate whether the
      intraoperative adjuvant therapy significantly influenced the prognosis, we
      reviewed changes in clinical factors by multiple regression analysis using the
      Cox's proportional hazard model. Ap value of less than 0.05 was considered
      statistically significant. RESULTS: The 3- and 5-year cumulative survival rates
      in patients who underwent intraoperative adjuvant therapy were 35.7% and 7.7%,
      while those in patients who underwent postoperative adjuvant therapy were 35.0%
      and 0%, respectively. The difference was not statistically significant. The level
      of a-fetoprotein, maximum tumor size, number of tumors, and clinical stage were
      found to be independent factors affecting survival after diagnosis.
      Intraoperative adjuvant therapy was not an independent prognostic factor.
      CONCLUSIONS: The survival rates did not differ between the patients who underwent
      intraoperative adjuvant therapy and postoperative adjuvant therapy for satellite
      lesions of non-resectable HCC.

PMID- 16608036
TI  - Overexpression of pituitary tumor-transforming gene-1 in hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: Pituitary tumor-transforming gene-1, a recently identified proto
      oncogene, was reported to be highly expressed in various tumors, such as tumors
      of the pituitary gland, adrenal gland, colon, ovary, endometrium, uterus, and
      kidney. The purpose of this study was to investigate the clinicopathologic
      significance of PTTG1 expression in hepatocellular carcinoma. METHODOLOGY:
      Expression of PTTG1 mRNA was evaluated by RT-PCR in 147 HCCs and 103 paired
      nontumorous liver tissues. RESULTS: PTTG1 was found overexpressed in 80 of 147
      (61%) HCCs. Overexpression of PTTG1 correlated with alpha-fetoprotein elevation
      (p<0.022) and higher tumor stage (stage IIIB-IV) tumors (p<0.009), but not with
      tumor grade, size, and survival. CONCLUSIONS: The results show that PTTG1 is
      overexpressed frequently in HCC, and correlated high stage tumors, indicating
      that overexpression of PTTG1 plays a role in the development and progression of
      HCC.

PMID- 16608037
TI  - Diffuse infiltrative hepatocellular carcinomas in a hepatitis B-endemic area:
      diagnostic and therapeutic impediments.
AB  - BACKGROUND/AIMS: Clinical features of diffuse infiltrative hepatocellular
      carcinoma (D-HCC) are distinct from those of mass-forming HCCs, and also
      dependent on etiologic viruses. Moreover, despite a regular HCC-surveillance in
      those with chronic liver diseases, patients sometimes present with advanced D
      HCCs. Thus, in the present study, we were to assess the risk factors, mode of
      diagnosis and prognosis of D-HCCs in a hepatitis B virus-endemic area.
      METHODOLOGY: From January to June 2003, 35 patients who had been newly diagnosed
      as having D-HCC were enrolled. Their clinical characteristics were compared with
      those with other types of HCCs, who had been enrolled during the same period.
      Survival rates were analyzed using Kaplan-Meier method and Cox proportional
      hazard model. RESULTS: D-HCC patients were younger and more commonly positive for
      HBsAg than those with other types of HCCs. During a regular follow-up, these
      tumors were not readily detectable in ultrasonography. Transarterial
      chemoembolization was beneficial in patients with good liver function as compared
      to supportive care, while this was not evident in those with poor hepatic
      reserve. CONCLUSIONS: D-HCCs are not readily diagnosed using ultrasonography.
      These tumors are mostly resistant to treatment, while transarterial
      chemoembolization might be applied in patients with good liver function.

PMID- 16608038
TI  - Usefulness of examination of some tumor markers in diagnostics of liver cancer.
AB  - BACKGROUND/AIMS: Diagnostics of liver cancer is mainly based on imaging methods:
      which are ultrasound and computer tomography. Determination of tumor markers is
      an accessory investigation enabling us to detect cancer, to evaluate the
      effectiveness of its operative and postoperative treatment and to diagnose early
      cancer relapse or distant metastases. Alpha-fetoprotein (AFP) is a basic well
      known marker in diagnostics of liver cancer. Carcinoembryonic antigen (CEA) and
      cancer procoagulant (CP) are also important in case of metastases to this organ,
      especially from the colon. The purpose of this study was to evaluate the
      usefulness of AFP, CEA and CP in detection of liver cancer. METHODOLOGY: The
      material of the study was the blood serum from 25 patients with liver cancer
      diagnosed histopathologically and 12 healthy individuals as a control group. The
      concentrations of AFP and CEP were assessed by immunoenzymatic method (MEIA) in
      the Axsym analyzer of Abbott and expressed in ng/mL. CP activity was determined
      by coagulation method worked out by Gordon and Benson and expressed as
      coagulation time in seconds (s). RESULTS: Based on the results obtained in our
      study, the concentrations of AFP and CEP were several fold higher in the serum of
      patients with liver cancer than the relevant values of these markers. CP activity
      was higher in the serum of patients with liver cancer than the mean values of
      patients in the control group. The differences found in the study between the
      groups examined and the control group were statistically significant atp<0.001.
      CONCLUSIONS: The results confirmed a high diagnostic value of AFP and CEA testing
      and suggest the possibility of using CP activity to detect liver cancer.

PMID- 16608039
TI  - Factors influencing survival in hepatocellular carcinoma patients with
      macroscopic portal vein tumor thrombosis after surgery, with special reference to
      time dependency: a single-center experience of 381 cases.
AB  - BACKGROUND/AIMS: The prognosis ofhepatocellular carcinoma with macroscopic portal
      vein tumor thrombosis is extremely poor. The risk factors may differ at different
      postoperative intervals. This study was undertaken to clarify the surgical
      outcome and time dependency of factors influencing survival in these patients.
      METHODOLOGY: We analyzed clinicopathological variables of 381 hepatocellular
      carcinoma patients with macroscopic portal vein tumor thrombosis who underwent
      hepatic resection. Survival rates were calculated using Kaplan-Meier method. The
      stratified Cox models were used to identify factors independently influencing
      short- and long-term survival, respectively. RESULTS: The cumulative 1-, 2-, 3-,
      5-, and 10-year survival rates in 381 patients were 47%, 23%, 16%, 12%, 6%,
      respectively. The 1-, 3-, and 5-year survival rates calculated from time of re
      resection were 36%, 14% and 0% in patients undergoing re-resection for
      intrahepatic recurrence within 2 years after first operation, and 85%, 53% and
      32% in those more than 2 years after first operation (P<0.05). Multivariate
      analysis showed that portal vein infusion chemotherapy, serum alpha-fetoprotein >
      20 mg/L and positive surgical margin were significant prognostic factors within 2
      years after operation. In contrast, alanine aminotransferase > 80 U/L was the
      only significant factor beyond 2 years after operation. CONCLUSIONS: The survival
      of hepatocellular carcinoma patients with macroscopic portal vein tumor
      thrombosis was poor, but the prognosis of patients who had tumor recurrence more
      than 2 years after operation was much better than those with tumor recurrence
      within 2 years. Evaluation of time-dependency of risk factors may have important
      clinical implication in determining the therapeutic strategy.

PMID- 16608040
TI  - Colchicine treatment of liver fibrosis.
AB  - BACKGROUND/AIMS: Because of its antifibrotic and anti-inflammatory effects,
      colchicine has been proposed as a treatment for liver disease. The results from
      clinical trials have however been inconsistent. The aim of the present study was
      to evaluate the effect of colchicine in the treatment of patients with hepatic
      fibrosis of various etiologies. METHODOLOGY: Thirty-eight patients were
      randomized to receive either colchicine 1 mg per day (n=21, group A) or no
      antifibrotic agent (n=17, group B). Treatment lasted for at least 12 months.
      Liver biopsy was performed prior to entry and after 12 months. Liver function
      tests, serum aminoterminal peptide of procollagen III (PIIINP) levels and CD4:CD8
      ratio of peripheral blood T lymphocytes (PBTLs) were performed at baseline and
      bimonthly or every 4 months post-treatment. RESULTS: Mean albumin serum levels
      increased 12 months post-treatment period only in group A (p<0.05). Mean serum
      PIIINP levels did not change significantly after 12 months of treatment in group
      A; in 7 patients a reduction in mean serum PIIINP levels was noticed during 24
      month post-treatment follow-up period (p<0.05). At baseline, a correlation
      between focal or bridging necrosis and CD4:CD8 ratio of PBTLs was noticed in
      group A (p < 0.05). The mean serum CD4:CD8 ratio was increased after 12 months of
      colchicine treatment (p<0.05) associated with abrogation of this correlation;
      comparison between the two groups revealed increased CD4:CD8 ratio in group A at
      12 months (p<0.05). The histological findings according to Knodell criteria in
      both groups remained unchanged after 12 months follow-up. The treatment was well
      tolerated in all patients. CONCLUSIONS: Long-term colchicine treatment in
      patients with hepatic fibrosis appears to exert an anti-inflammatory, anti
      fibrotic and immunomodulatory effect.

PMID- 16608041
TI  - Clinicopathological and immunohistochemical analysis of malignant features in
      mucinous cystic tumors of the pancreas.
AB  - BACKGROUND/AIMS: To investigate the malignancy of mucinous cystic tumors (MCTs)
      of the pancreas, we examined clinicopathological features and immunohistochemical
      findings of MCT. METHODOLOGY: We analyzed the expression of p53 protein,
      proliferating cell nuclear antigen, alpha6-integrin subunit, alpha5beta1
      integrin, and interleukin-1 receptor type I in tumor specimens from eight
      patients with MCT. RESULTS: The tumors were classified as mucinous cyst adenoma
      (n=6) or mucinous cyst adenocarcinoma (n=2). The actuarial five-year survival
      rate was 83.3%. All in eight MCTs had 'ovarian-type' stroma in the cyst wall. The
      alpha6-integrin subunit and p53 protein were expressed in adenocarcinoma tissues
      of MCTs, and in two adenomas the alpha6-integrin subunit and p53 protein were
      also co-expressed. CONCLUSIONS: Our present results indicate that coexpression of
      the alpha6-integrin subunit and p53 protein should be appreciated as an indicator
      of malignancy in MCTs.

PMID- 16608042
TI  - Malignant solid and pseudopapillary tumor of the pancreas--clinicohistological,
      immunohistochemical, and flow cytometric evaluation.
AB  - BACKGROUND/AIMS: Solid and pseudopapillary tumor of the pancreas is a benign and
      low malignant potential tumor. Prognosis is good after surgical resection but its
      malignant potential is usually defined after metastasis. We compared benign and
      malignant cases with clinicopathological, immunohistochemical and DNA flow
      cytometric studies. METHODOLOGY: From January 1991 to July 2004, seven patients
      were found to have solid and pseudopapillary tumor of the pancreas at Taipei
      Veterans General Hospital. The paraffin sections were reevaluated with
      hematoxylin & eosin stain, immunohistochemical stains, and DNA flow cytometric
      studies. RESULTS: It included 6 benign and one malignant case. The progesterone
      receptor, vimentin, neuron-specific enolase, and chromogranin A showed diffused
      positive stain in all cases. Estrogen receptor and P53 stain were negative in all
      7 patients. Synaptophysin stain was negative in 6 no recurrence patients, but was
      positive only in the patient who suffered from recurrence. DNA flow cytometry
      showed diploid results in six non-malignant tumors. In the malignant patient, the
      tumor in the first operation showed diploid result, but tumors in second and
      third operations showed aneuploidy. CONCLUSIONS: Solid and pseudopapillary tumor
      of the pancreas should be considered as a potentially malignant disease in all
      patients and regular follow-up is mandatory.

PMID- 16608043
TI  - A modified reconstruction method to prevent critical complications after
      pancreatoduodenectomy.
AB  - BACKGROUND/AIMS: A new method of reconstructing the pancreatic stump after
      pancreatoduodenectomy (PD) is necessary to improve the postoperative mortality
      rate. Thus, we modified the pancreatoenteric procedure to reduce anastomotic
      leakage from the pancreatic stump after PD, and we conducted a study to evaluate
      the usefulness of the new procedure on the basis of patients' postoperative
      condition. METHODOLOGY: We compared the postoperative condition of 21 patients
      who underwent PD with the new separated loop (SL) reconstruction (6 men, 11
      women; mean age, 67.7+/-7.2 years) to that of 31 patients (12 men, 19 women; mean
      age, 66.8+/-10.3 years) who underwent PD with pancreatogastrostomy (PG). In the
      SL reconstruction procedure, the proximal jejunum is brought up behind the colon,
      and an end-to-side choledochojejunostomy is made with a single layer of
      interrupted sutures. Approximately 20cm of the jejunum is fitted with a fixed
      stomach tube for postoperative enteral feeding, and the cut proximal jejunum is
      positioned next to the pancreatic stump. A pancreatic tube is inserted into the
      lumen of the pancreatic duct and fixed without closing the pancreatic duct.
      Pancreatojejunostomy is achieved as an end-to-end anastomosis with the pancreatic
      stump telescoping into the proximal jejunum. Approximately 20cm of the jejunum is
      anastomosed side-to-end to the stomach, and end-to-side jejunojejunostomy is made
      to complete a Y-type reconstruction. Each patient's postoperative condition was
      also assessed on the basis of serum albumin (ALB), cholinesterase and total
      cholesterol (T-CHO) levels on postoperative days (PODs) 14 and 28. RESULTS: A
      high level of amylase in drainage fluid was noted in two (6.5%) and delayed
      gastric emptying in four (12.9%) of the patients in the PG group. There were no
      complications in the SL group. Postoperative levels of ALB on POD 14 and T-CHO on
      POD 28 were significantly higher than in the PG group. CONCLUSIONS: The SL method
      is safe and does not induce complications after PD. Our results indicate that
      this method may provide a favored outcome.

PMID- 16608044
TI  - Evaluation of reconstruction after proximal gastrectomy: prospective comparative
      study of jejunal interposition and jejunal pouch interposition.
AB  - BACKGROUND/AIMS: To prevent various distresses after proximal gastrectomy,
      reconstruction by interposed jejunal pouch has been advocated as an organ
      preserving surgical strategy to ensure favorable quality of life for the
      patients. METHODOLOGY: Proximal gastrectomy was performed in 9 patients with
      gastric cancer in the upper third of the stomach. Four patients were randomly
      selected for reconstruction by jejunal pouch interposition (JPI group), while 5
      had reconstruction by jejunal interposition (JI group). The patients who
      underwent JPI and JI were followed up to evaluate resumption of normal diet,
      change in body weight, and clinical symptoms. RESULTS: The JPI group showed a
      significant dietary advantage. Three months after surgery, JPI patients could eat
      more than 80% of the volume of their preoperative meals, whereas JI patients ate
      less than 50%. The percentage of postoperative body weight loss was higher in the
      JI group than in the JPI group because the volume of the remnant stomach was more
      adequate in the latter. Moreover, it was easier to enter the remnant stomach and
      duodenum for endoscopic fiberscopy in the JPI group for the treatment of hepato
      biliary pancreatic disease. CONCLUSIONS: JPI is an effective method for
      preservation of gastric function after proximal gastrectomy.

PMID- 16608045
TI  - Long-term results of laparoscopic extended surgery in advanced gastric cancer: a
      series of 101 patients.
AB  - BACKGROUND/AIMS: The objective of our paper is to report on the remote results of
      patients with gastric cancer treated by mini-invasive surgery as a surgical tool
      with the "intention to treat with laparoscopy". METHODOLOGY: Between June 1993
      and January 2004, 101 patients comprising 72 men and 29 women with gastric
      adenocarcinoma were prospectively selected by two hospitals based on prior
      agreement (the CHU Charleroi, Belgium, and Zumarraga Hospital, the Basque
      Country, Spain). Patients with adenocarcinoma of the cardia were excluded.
      Average age of the patients was 67 (37-83). RESULTS: Postoperative mortality
      within 60 days of operation was of 5 patients; 87 patients were therefore
      properly followed-up for an average of 41 months (7-129). Average survival time
      for 10 non-resected patients was 4.5 months. Average survival rate of the 10
      palliatively resected patients was 7.1 months. Actuarial 5-year survival rate RO
      type surgery was 34%. The global actuarial 5-year survival rate after resective
      surgery was 29%. CONCLUSIONS: Laparoscopic gastrectomy with any kind of
      lymphadenectomy is a heavy but safe operation, and produces acceptable mortality
      and morbidity rates in patients with advanced gastric cancer in a general poor
      condition. Laparoscopic gastrectomies for locally advanced cancers are equivalent
      to those reported by laparotomy as far as long-term oncological results are
      concerned.

PMID- 16608046
TI  - Radical operation for recurring gastric carcinoma.
AB  - BACKGROUND/AIMS: The effectiveness of surgical treatment for recurring gastric
      carcinoma is unclear. We conducted a retrospective review of our results with a
      radical surgical approach to the treatment of gastric cancer metastases.
      METHODOLOGY: Nine patients who underwent radical resection of recurring gastric
      cancer between 1990 and 2003 were examined and follow-up was completed by March
      2003. RESULTS: The surgically removed recurring sites included local lesions (4
      patients), as well as metastases in the liver (4 patients) and ovary (1 patient).
      There were no major complications or operative deaths. The mean operative time
      was 380 minutes; the mean intraoperative blood loss was approximately 525mL and
      the mean volume of transfused blood was 178mL. Re-recurrence appears in 8
      patients between 1.5 and 26 months (average 8.5 months) following surgical
      resection. The sites of re-recurrence included the peritoneum, liver, lymph
      nodes, bone, as well as local lesions. One patient currently shows no evidence of
      disease more than 6 years after resection of the local recurrence. Two other
      patients remain alive, but presented with re-recurrence at 4 and 10 months
      postoperatively. The remaining 6 patients died of cancer between 2 and 28 months
      after surgery for recurring lesions. CONCLUSIONS: Radical surgery for recurring
      gastric cancer both liver and extrahepatic lesions is a safe treatment with a
      good prognosis for long-term survival in a select patient subpopulation.

PMID- 16608047
TI  - Clinicopathological features of type 1 gastric carcinoma: the need to be cautious
      of superficial lesion surrounding type 1 gastric carcinoma.
AB  - BACKGROUND/AIMS: Gastric carcinoma (GC) is one of the most common malignant
      tumors of the digestive tract and the incidence of adenocarcinoma of the upper
      one-third of the stomach has increased recently worldwide. The objective of this
      study was to analyze the clinicopathological variables in patients with GC and
      examine preoperative diagnosis and the medical treatment strategy of Type 1 GC.
      METHODOLOGY: Nine hundred and eighty-one patients with GC who underwent surgical
      resection between 1981 and 2002 at Kochi Medical School were studied. Thirty-five
      patients with Type 1 GC were compared with non-Type 1 GC patients on
      postoperative surgicopathological parameters, and changing trends were evaluated.
      RESULTS: The characteristics of patients with Type 1 GC were different from those
      of patients with non-Type 1 GC: Their tumors were more often in the upper one
      third of the stomach (37% vs. 15%), lesions were histologically differentiated in
      80% (vs. 56%), and there were more superficial lesions surrounding Type 1 GC (80%
      vs. 8%). The absolute value and the rate of Type 1 GC increased significantly
      from the first half to the second half of the study. CONCLUSIONS: Our findings
      showed that when Type 1 GC is discovered, physicians should investigate the
      mucosa around the main neoplasm carefully. The current series suggested that Type
      1 GC are associated frequently with superficial lesions, making local resections
      more difficult, and that Type 1 GC was similar clinicopathologically to carcinoma
      of the gastric cardia and had different etiologies contributed to its
      tumorgenesis, compared with non-Type 1 GC, and Type 1 GC may become the key which
      solves the problem of carcinoma at the gastric cardia.

PMID- 16608048
TI  - Diabetic peripheral neuropathic pain: clinical and quality-of-life issues.
AB  - Diabetic peripheral neuropathy (DPN) is estimated to be present in 50% of people
      living with diabetes mellitus (DM). Comorbidities of DM, such as macrovascular
      and microvascular changes, also Interact with DPN and affect its course. In
      patients with DM, DPN Is the leading cause of foot ulcers, which in turn are a
      major cause of amputation in the United States. Although most patients with DPN
      do not have pain, approximately 11% of patients with DPN have chronic, painful
      symptoms that diminish quality of life, disrupt sleep, and can lead to
      depression. Despite the number of patients affected by DPN pain, little consensus
      exists about the pathophysiology, best diagnostic tools, and primary treatment
      choices. This article reviews the current knowledge about and presents
      recommendations for diagnostic assessment of DPN pain based on a review of the
      literature.

PMID- 16608049
TI  - Consensus guidelines: treatment planning and options. Diabetic peripheral
      neuropathic pain.
AB  - Despite the number of patients affected by diabetic peripheral neuropathic pain
      (DPNP), little consensus exists about the pathophysiology, best diagnostic tools,
      and primary treatment choices. Theories about the causes of DPNP are inextricably
      linked with the causes of diabetic neuropathles, yet most patients with such
      neuropathies do not experience pain. The factors that differentiate patients with
      pain from those without remain unknown and are the subject of much research. When
      choosing treatment for patients with DPNP, physicians are confronted with a
      myriad of choices, none of which has been shown to be effective for all patients.
      This article reviews the evidence for these treatments and attempts to guide
      physicians in choosing those treatments based on evidence from well-designed
      clinical trials to support their use. Two agents, duloxetine and pregabalin, are
      formally approved by the Food and Drug Administration for the treatment of DPNP.
      In addition, several other agents, including the tricyclic class of
      antidepressants, have been effective in clinical trials. Ultimately, treatment
      choice must also Include consideration of adverse effects, individual patient
      factors such as comorbidities, and often cost.

PMID- 16608050
TI  - Diabetic peripheral neuropathic pain: case studies.
AB  - Three case reports in this article illustrate the diagnostic methods used and the
      treatment course encountered for many patients with diabetic peripheral
      neuropathic pain (DPNP). Each case addresses an aspect of DPNP: pain that appears
      to be refractory to initial therapy, DPNP occurring with other medical
      conditions, and nondiabetlc neuropathy occurring in patients with diabetes
      mellitus. Together, these cases bring clarity to the confusing clinical
      experience for patients who have decreased sensation in combination with burning
      pain, and they apply the consensus guidelines for DPNP. Recently approved
      medications by the Food and Drug Administration for the treatment of DPNP offer
      hope for many patients whose pain was thought to be refractory to treatment.

PMID- 16608051
TI  - Clinical results of Cerec inlays in a dental practice over a period of 18 years.
AB  - In a German dental practice, 299 patients were treated with 1011 ceramic fillings
      between June 1987 and October 1990. The restorations were produced according to
      the Cerec method and in each case inserted adhesively at the same appointment.
      The clinical success was continuously observed and documented. The period in
      place was between 15 and 18 years. Event criteria were loss of the tooth or of
      the restoration, fracture with partial loss of tooth and/or restoration, marginal
      caries, marginal repair and endodontic complication. The probability of success
      according to the Kaplan-Meier method was reduced after 16.7 years to a value of
      84.4%. No further event was observed up to the final time of 18.3 years. If
      "restoration still in place" is made the basis for the survival analysis, ie,
      therapeutic measures such as trepanation and marginal correction with composite
      remain unconsidered, then the Kaplan-Meier value for the observation period is
      89%. The size of the filling had no influence on the success prognosis. Premolars
      achieved a better result than molars. Vital teeth prove to be better than non
      vital teeth. The use of dentin adhesives increased the probability of success. A
      total of 121 events, 86 of these losses of restoration, occurred in the
      observation interval. The most frequent causes were ceramic and tooth fractures.

PMID- 16608052
TI  - Comparison of static and dynamic computer-assisted guidance methods in
      implantology.
AB  - The planning of dental implant position and its transfer to the operation site
      can be considered as one of the most important factors for the long-term success
      of implant-supported prosthetic and epithetic restorations. This study compares
      computer-assisted fabricated surgical templates as the static method with intro
      operative image guided navigation as the dynamic method for transfer of three
      dimensional pre-operative planning. For the static method, the systems Med3D,
      coDiagnostix/ gonyX, and SimPlant were used. For the dynamic method, the systems
      RoboDent und VectorVision2 were applied. A total of 746 implants were inserted
      between August 1999 and December 2005 in 206 patients. The static approach was
      used most frequently, accounting for 611 fixtures in 168 patients. The failure
      ratios within the first 6 months were 1.31% in the statically controlled
      insertion group compared to 2.96% in the dynamically controlled insertion group.
      Complications related to an incorrect position of the implants have not been
      observed so far in either group. All computer-assisted methods included in this
      study were successfully applied in a clinical setting after a certain start-up
      period. The indications for application of computer-assisted methods in
      implantology are currently given in difficult anatomical situations. Due to
      uncomplicated handling and low resource demands, the static template technique
      can be recommended as the method of choice for the majority of all cases falling
      into this category.

PMID- 16608053
TI  - What a difference 20 years make.

PMID- 16608054
TI  - Current practice in conventional and digital intraoral radiography: problems and
      solutions.
AB  - In summary, it can be said for digital radiography that digital exposures can be
      taken just as well as dental film exposures. The problems found when using
      holders for the paralleling technique are similar in conventional and digital
      radiography. Good intraoral x-ray images can be produced as a rule with practice,
      good will and a skilful hand. The bisected angle technique should no longer be
      used, as this no longer corresponds to the state of the art and of dental
      medicine. It is therefore important that all intraoral dental exposures are taken
      with corresponding holders and the paralleling technique. Thus, the bite wing and
      measuring exposures are no longer taken with the finger or other aids, but
      suitable holders are used. However, being able to place the film, the storage
      phosphor or the sensor in the oral cavity correctly is just as important as the
      choice of exposure technique. Theoretical knowledge and practical skill are
      therefore closely related.

PMID- 16608055
TI  - Multicolored ceramic blocks as an esthetic solution for anterior restorations.

PMID- 16608056
TI  - Computer analysis of computed tomography scans of the lung: a survey.
AB  - Current computed tomography (CT) technology allows for near isotropic,
      submillimeter resolution acquisition of the complete chest in a single breath
      hold. These thin-slice chest scans have become indispensable in thoracic
      radiology, but have also substantially increased the data load for radiologists.
      Automating the analysis of such data is, therefore, a necessity and this has
      created a rapidly developing research area in medical imaging. This paper
      presents a review of the literature on computer analysis of the lungs in CT scans
      and addresses segmentation of various pulmonary structures, registration of chest
      scans, and applications aimed at detection, classification and quantification of
      chest abnormalities. In addition, research trends and challenges are identified
      and directions for future research are discussed.

PMID- 16608057
TI  - Image-processing technique for suppressing ribs in chest radiographs by means of
      massive training artificial neural network (MTANN).
AB  - When lung nodules overlap with ribs or clavicles in chest radiographs, it can be
      difficult for radiologists as well as computer-aided diagnostic (CAD) schemes to
      detect these nodules. In this paper, we developed an image-processing technique
      for suppressing the contrast of ribs and clavicles in chest radiographs by means
      of a multiresolution massive training artificial neural network (MTANN). An MTANN
      is a highly nonlinear filter that can be trained by use of input chest
      radiographs and the corresponding "teaching" images. We employed "bone" images
      obtained by use of a dual-energy subtraction technique as the teaching images.
      For effective suppression of ribs having various spatial frequencies, we
      developed a multiresolution MTANN consisting of multiresolution
      decomposition/composition techniques and three MTANNs for three different
      resolution images. After training with input chest radiographs and the
      corresponding dual-energy bone images, the multiresolution MTANN was able to
      provide "bone-image-like" images which were similar to the teaching bone images.
      By subtracting the bone-image-like images from the corresponding chest
      radiographs, we were able to produce "soft-tissue-image-like" images where ribs
      and clavicles were substantially suppressed. We used a validation test database
      consisting of 118 chest radiographs with pulmonary nodules and an independent
      test database consisting of 136 digitized screen-film chest radiographs with 136
      solitary pulmonary nodules collected from 14 medical institutions in this study.
      When our technique was applied to nontraining chest radiographs, ribs and
      clavicles in the chest radiographs were suppressed substantially, while the
      visibility of nodules and lung vessels was maintained. Thus, our image-processing
      technique for rib suppression by means of a multiresolution MTANN would be
      potentially useful for radiologists as well as for CAD schemes in detection of
      lung nodules on chest radiographs.

PMID- 16608058
TI  - Morphological segmentation and partial volume analysis for volumetry of solid
      pulmonary lesions in thoracic CT scans.
AB  - Volumetric growth assessment of pulmonary lesions is crucial to both lung cancer
      screening and oncological therapy monitoring. While several methods for small
      pulmonary nodules have previously been presented, the segmentation of larger
      tumors that appear frequently in oncological patients and are more likely to be
      complexly interconnected with lung morphology has not yet received much
      attention. We present a fast, automated segmentation method that is based on
      morphological processing and is suitable for both small and large lesions. In
      addition, the proposed approach addresses clinical challenges to volume
      assessment such as variations in imaging protocol or inspiration state by
      introducing a method of segmentation-based partial volume analysis (SPVA) that
      follows on the segmentation procedure. Accuracy and reproducibility studies were
      performed to evaluate the new algorithms. In vivo interobserver and interscan
      studies on low-dose data from eight clinical metastasis patients revealed that
      clinically significant volume change can be detected reliably and with negligible
      computation time by the presented methods. In addition, phantom studies were
      conducted. Based on the segmentation performed with the proposed method, the
      performance of the SPVA volumetry method was compared with the conventional
      technique on a phantom that was scanned with different dosages and reconstructed
      with varying parameters. Both systematic and absolute errors were shown to be
      reduced substantially by the SPVA method. The method was especially successful in
      accounting for slice thickness and reconstruction kernel variations, where the
      median error was more than halved in comparison to the conventional approach.

PMID- 16608059
TI  - On measuring the change in size of pulmonary nodules.
AB  - The pulmonary nodule is the most common manifestation of lung cancer, the most
      deadly of all cancers. Most small pulmonary nodules are benign, however, and
      currently the growth rate of the nodule provides for one of the most accurate
      noninvasive methods of determining malignancy. In this paper, we present methods
      for measuring the change in nodule size from two computed tomography image scans
      recorded at different times; from this size change the growth rate may be
      established. The impact of partial voxels for small nodules is evaluated and
      isotropic resampling is shown to improve measurement accuracy. Methods for nodule
      location and sizing, pleural segmentation, adaptive thresholding, image
      registration, and knowledge-based shape matching are presented. The latter three
      techniques provide for a significant improvement in volume change measurement
      accuracy by considering both image scans simultaneously. Improvements in
      segmentation are evaluated by measuring volume changes in benign or slow growing
      nodules. In the analysis of 50 nodules, the variance in percent volume change was
      reduced from 11.54% to 9.35% (p = 0.03) through the use of registration, adaptive
      thresholding, and knowledge-based shape matching.

PMID- 16608060
TI  - Local noise weighted filtering for emphysema scoring of low-dose CT images.
AB  - Computed tomography (CT) has become the new reference standard for quantification
      of emphysema. The most popular measure of emphysema derived from CT is the pixel
      index (PI), which expresses the fraction of the lung volume with abnormally low
      intensity values. As PI is calculated from a single, fixed threshold on
      intensity, this measure is strongly influenced by noise. This effect shows up
      clearly when comparing the PI score of a high-dose scan to the PI score of a low
      dose (i.e., noisy) scan of the same subject. In this paper, the noise variance
      (NOVA) filter is presented: a general framework for (iterative) nonlinear
      filtering, which uses an estimate of the spatially dependent noise variance in an
      image. The NOVA filter iteratively estimates the local image noise and filters
      the image. For the specific purpose of emphysema quantification of low-dose CT
      images, a dedicated, noniterative NOVA filter is constructed by using prior
      knowledge of the data to obtain a good estimate of the spatially dependent noise
      in an image. The performance of the NOVA filter is assessed by comparing
      characteristics of pairs of high-dose and low-dose scans. The compared
      characteristics are the PI scores for different thresholds and the size
      distributions of emphysema bullae. After filtering, the PI scores of high-dose
      and low-dose images agree to within 2%-3% points. The reproducibility of the high
      dose bullae size distribution is also strongly improved. NOVA filtering of a CT
      image of typically 400 x 512 x 512 voxels takes only a couple of minutes which
      makes it suitable for routine use in clinical practice.

PMID- 16608061
TI  - MDCT-based 3-D texture classification of emphysema and early smoking related lung
      pathologies.
AB  - Our goal is to enhance the ability to differentiate normal lung from subtle
      pathologies via multidetector row CT (MDCT) by extending a two-dimensional (2-D)
      texturebased tissue classification [adaptive multiple feature method (AMFM)] to
      use three-dimensional (3-D) texture features. We performed MDCT on 34 humans and
      classified volumes of interest (VOIs) in the MDCT images into five categories:
      EC, emphysema in severe chronic obstructive pulmonary disease (COPD); MC, mild
      emphysema in mild COPD; NC, normal appearing lung in mild COPD; NN, normal
      appearing lung in normal nonsmokers; and NS, normal appearing lung in normal
      smokers. COPD severity was based upon pulmonary function tests (PFTs). Airways
      and vessels were excluded from VOIs; 24 3-D texture features were calculated; and
      a Bayesian classifier was used for discrimination. A leave-one-out method was
      employed for validation. Sensitivity of the four-class classification in the form
      of 3-D/2-D was: EC: 85%/71%, MC: 90%/82%; NC: 88%/50%; NN: 100%/60%. Sensitivity
      and specificity for NN using a two-class classification of NN and NS in the form
      of 3-D/2-D were: 99%/72% and 100%/75%, respectively. We conclude that 3-D AMFM
      analysis of lung parenchyma improves discrimination compared to 2-D AMFM of the
      same VOIs. Furthermore, our results suggest that the 3-D AMFM may provide a means
      of discriminating subtle differences between smokers and nonsmokers both with
      normal PFTs.

PMID- 16608062
TI  - Lung motion correction on respiratory gated 3-D PET/CT images.
AB  - Motion is a source of degradation in positron emission tomography (PET)/computed
      tomography (CT) images. As the PET images represent the sum of information over
      the whole respiratory cycle, attenuation correction with the help of CT images
      may lead to false staging or quantification of the radioactive uptake especially
      in the case of small tumors. We present an approach avoiding these difficulties
      by respiratory-gating the PET data and correcting it for motion with optical flow
      algorithms. The resulting dataset contains all the PET information and minimal
      motion and, thus, allows more accurate attenuation correction and quantification.

PMID- 16608063
TI  - Nonlinear motion correction of respiratory-gated lung SPECT images.
AB  - We propose a method for correcting the motion of the lungs between different
      phase images obtained by respiratory-gated single photon emission computed
      tomography (SPECT). This method is applied to SPECT images that show a preserved
      activity distribution in the lungs such as 99m-Tc macro aggregated albumin (99m
      Tc-MAA) perfusion images and 99m-Tc-Technegas ventilation images. In the proposed
      method, an objective function, which consists of both the degree of similarity
      between a reference image and a deformed image, and the smoothness of deformation
      is defined and optimized using a simulated annealing algorithm. For the degree of
      similarity term in the objective function, an expansion ratio, defined as the
      ratio of change in local volume due to deformation, is introduced to preserve the
      total activity during the motion correction process. This method was applied to
      data simulated from computer phantoms, data acquired from a physical phantom, and
      17 sets of clinical data. In all cases, the motion correction between inspiration
      and expiration phase images was successfully achieved.

PMID- 16608064
TI  - An alternate line erasure and readout (ALER) method for implementing slot-scan
      imaging technique with a flat-panel detector--initial experiences.
AB  - This paper describes and demonstrates an electronic collimation method, referred
      to as the alternate line erasure and readout (ALER) technique, for implementing
      slot-scan digital radiography technique with an amorphous silicon (a-Si) thin
      film transistor (TFT) array based flat-panel detector. An amorphus selenium (a
      Se) flat-panel detector was modified to implement the ALER technique for slot
      scan imaging. A stepping-motor driven fore-collimator was mounted in front of an
      X-ray tube to generate a scanning X-ray fan beam. The scanning speed and
      magnification were adjusted to synchronize the fan beam motion with the image
      line readout rate. The image lines on the leading and trailing edges of the fan
      beam were tracked and alternately reset and read out, respectively. The former
      operation resulted in the erasure of the scatter signals accumulated in the
      leading edge image line prior to the arrival of the fan beam. The latter
      operation resulted in the acquisition of fan beam exposure data integrated in the
      trailing edge image line right after the fan beam passed. To demonstrate the
      scatter rejection capability of this technique, an anthropomorphic chest phantom
      was placed in PA position and scanned at a speed of 576 lines (8.0 cm)/s at 117
      kVp and 32 mA. A tungsten bar is placed at the entrance side of the chest phantom
      to measure the scatter-to-primary ratio (SPR), scatter reduction factor (SRF),
      and contrast-to-noise ratio degradation factor (CNRDF) in the slot-scan images to
      evaluate the effectiveness of scatter rejection and the resultant improvement of
      image quality. SPR and CNRDF in the open-field images were also measured and used
      as the reference for comparison. A scatter reduction by 86.4 to 95.4% across
      lower lung and heart regions has been observed with slot-scan imaging. The CNRs
      have been found to be improved by a factor of 2 in the mediastinum areas over the
      open-field image as well.

PMID- 16608065
TI  - Patient-specific bronchoscopy visualization through BRDF estimation and
      disocclusion correction.
AB  - This paper presents an image-based method for virtual bronchoscope with photo
      realistic rendering. The technique is based on recovering bidirectional
      reflectance distribution function (BRDF) parameters in an environment where the
      choice of viewing positions, directions, and illumination conditions are
      restricted. Video images of bronchoscopy examinations are combined with patient
      specific three-dimensional (3-D) computed tomography data through two-dimensional
      (2-D)/3-D registration and shading model parameters are then recovered by
      exploiting the restricted lighting configurations imposed by the bronchoscope.
      With the proposed technique, the recovered BRDF is used to predict the expected
      shading intensity, allowing a texture map independent of lighting conditions to
      be extracted from each video frame. To correct for disocclusion artefacts,
      statistical texture synthesis was used to recreate the missing areas. New views
      not present in the original bronchoscopy video are rendered by evaluating the
      BRDF with different viewing and illumination parameters. This allows free
      navigation of the acquired 3-D model with enhanced photo-realism. To assess the
      practical value of the proposed technique, a detailed visual scoring that
      involves both real and rendered bronchoscope images is conducted.

PMID- 16608066
TI  - Constructing the eukaryotic expression vector to study preliminarily the
      functions of hammerhead ribozyme targeting base excision repair gene HOGG1.
AB  - OBJECTIVE: Adriamycin is widely used as an effective anti-tumor drug clinically
      treating a number of human cancers, but the effect of adriamycin is limited by
      drug resistance. The various kinds of investigations indicated that the anti
      tumor activity of adriamycin resulted from drug-induced free radical formation.
      The free radicals could lead to oxidative DNA damage, and the lesion would be
      repaired by base excision repair (BER) pathway. Human 8-oxoguanine DNA
      glycosylase 1 (HOGG1) is a key enzyme on BER pathway. To study the influence and
      biological mechanism of the HOGG1 to adriamycin drug-sensitivity, the eukaryotic
      expression vector with gene of hammerhead ribozyme targeting HOGG1 mRNA would be
      constructed and identified, and then the change of drug-sensitivity in lung
      cancer A549 cells would be investigated. METHODS: According to computer design,
      two specific restriction site BamH I and EcoR I were added to both ends of the
      ribozyme gene, then the modified ribozyme gene was synthesized and cloned into
      the eukaryotic expression vector pcDNA3.1 (+). The positive recombinants were
      screened by ampicillin resistance, and plasmids were extracted from the positive
      recombinants and digested by BamH I and EcoR I , and then were analyzed by
      agarose gel electrophoresis and DNA sequencing. The recombinants were transiently
      transfected into A549 cells. The positive recombinants were identified by reverse
      transcription-polymerase chain reaction (RT-PCR) targeting to NEO gene, which was
      a neomycin resistance gene for selection of stable cell lines and only existed in
      vectors. The changes of HOGG1 mRNA in A549 cells were detected by RT-PCR. Then
      the cellular sensitivity to adriamycin was tested by comparison between
      untransfected cells and transfected cells by MTT assay. The adriamycin-induced
      DNA damage was investigated by comet assay or single cell gel electrophoresis
      (SCGE) between untransfected and transfected cells. RESULTS: The recombinants
      containing the ribozyme gene were successfully selected by restriction
      endonuclease digestion and agarose gel electrophoresis, and were further proved
      by DNA automatic sequencing. A549 cells containing the recombinants were
      identified by RT-PCR, because NEO genes were amplified only in cells transfected
      successfully. The expression of HOGG1 mRNA in A549 transfected with ribozyme gene
      was 36% significantly less than in control cells (P < 0.05). MTT assay showed
      that the sensitivity of transfected cells to adriamycin were significantly
      increased in comparison with untransfected cells (P < 0.05). The comet assay
      showed that the extent of DNA damage induced by adriamycin was worse in
      transfected cells than unrtransfected cells (P < 0.05), but there was no time
      dependent reaction correlation observed in cells. CONCLUSION: The eukaryotic
      expression vector with gene of hammerhead ribozyme targeting HOGG1 mRNA was
      constructed successfully, and effectively inhibited the expression of HOGG1 gene
      in lung cancer A549 cells, and increased the cellular sensitivity to adriamycin,
      and will help to study deeply the functions of base excision repair genes-HOGG1.

PMID- 16608067
TI  - The expression of maxiK channel alpha--subunit during human macrophages
      differentiating into foam cells.
AB  - OBJECTIVE: To investigate the expression of MaxiK channel alpha-subunit during
      human monocyte-derived macrophages differentiating into foam cells. METHODS:
      Human peripheral blood monocytes were isolated from male healthy volunteers by
      density gradient centrifugation, which, by culture, differentiated further into
      macrophages as a homogeneous monocyte population. The foam cell model originated
      from human macrophage was established by incubating macrophages with oxidized low
      density lipoprotein (OxLDL). The expression of MaxiK channel alpha-subunit was
      investigated by RT-PCR techniques, Western blotting and immunocytochemistry.
      RESULTS: After incubating macrophages with 30 mg/L OxLDL for 60 hours, the
      cellular contents of total cholesterol (TC), free cholesterol (FC) and
      cholesterol ester (CE) were markedly increased and the ratio of CE/TC was further
      raised from (14.437 +/- 6.781) % to (57.946 +/- 3.507) %. Although the expression
      of MaxiK channel alpha-subunit was downregulated during human monocyte-derived
      macrophages differentiating into foam cells, there was no significant difference
      between macrophages and foam cells (P > 0.05). CONCLUSION: That 30 mg/L OxLDL can
      lead the monocyte-derived macrophage cultured for 60 hours to differentiate into
      foam cell, but the expression of MaxiK channel alpha-subunit does not change
      obviously.

PMID- 16608068
TI  - [Construction of eukaryotic expressing plasmids for HA and HA1 of influenza A
      virus and their transient expression in HEK293 cells].
AB  - OBJECTIVE: To construct influenza A virus (A/PR/8/34) HA and HA1 eukaryotic
      expressing plasmids and study their expression in HEK293 cells. METHODS: HA and
      HA1 genes were cloned by RT-PCR and then inserted into pcDNA3. 1 (+). After
      identification of restriction enzyme digestion, PCR and sequencing analysis, HA
      and HA1 eukaryotic expressing plasmids were transfected into HEK293 cells with
      PolyFect Transfection Reagent. Immunofluorescence assay was used to observe the
      transient expressing result. RESULTS: It was confirmed that the construction of
      HA and HA1 eukaryotic expressing plasmids was made successfully. The stronger
      fluorescence signals were detected in transfected HEK293 cells with these two
      kinds of plasmids by immunofluorescence assay. CONCLUSION: The experiment is a
      success in the construction of eukaryotic expressing plasmids for HA and HA1,
      thus providing a basis for further probing into the mechanism of virus infection
      and exploring DNA vaccine.

PMID- 16608069
TI  - [On the relationship between exopolysaccharides and Actinomyces viscosus in
      biofilms].
AB  - OBJECTIVE: To elucidate the biofilm structure of Actinomyces viscosus and the
      spatial distribution of exopolysaccharides in it. METHODS: The Actinomyces
      viscosus biofilm was made by allowing bacteria to attach to the cover glass
      surface. The biofilm structure and exopolysaccharides distribution at 24 hours
      were stained with Fluorescein, BODIPY and Calcofluor respectively and were
      visualized by confocal laser scanning microscopy (CLSM). RESULTS: Actinomyces
      viscosus could attach to glass surface and form a structural biofilm where
      bacteria were embedded in the EPS glycocalyx polymers, and characteristic
      microcolonies and channels were taking shape. Bacteria were sparse in the
      substratum area but crowd in the center. In the biofilm, the distribution of
      bacteria was consistent with the distribution of exopolysaccharides. CONCLUSION:
      The findings demonstrate an important role of exopolysaccharides in the process
      of Actinomyces viscosus biofilm formation.

PMID- 16608070
TI  - [Viral transactivation of transcription by NF-kappaB in steroid-responsive simple
      nephrotic syndrome].
AB  - OBJECTIVE: To investigate the path of viral transactivation of transcription by
      nuclear factor-kappa B (NF-kappaB) in the pathogenesis of steroid-responsive
      simple nephrotic syndrome (SRSNS) triggered by respiratory tract viruses.
      METHODS: Children with SRSNS (including active stage, convalescent and remissive
      stage) were examined and were analytically compared to children with nephritic
      nephrosis, secondary glomerular diseases and bronchiolitis; healthy children were
      enrolled as controls. The methods of electrophoretic mobility shift assay (EMSA),
      of reverse transcription-PCR (RT-PCR), and of enzyme-linked immunosorbent assay
      (ELISA), were used to detect the transcriptive activity of NF-kappaB, the gene
      expression of respiratory tract viruses (respiratory syncytial virus-RSV,
      influenza virus-Flu) in peripheral blood mononuclear cells (PBMC), and the levels
      of IL-8 and viral antibodyies in serum, respectively. RESULTS: (1) Compared with
      the control and SRSNS in convalescent and remissive stage, the activity of NF
      kappaB in PBMC of SRSNS in active stage was statistically elevated (P<0.05).
      (2)The level of IL-8 in serum of SRSNS in active stage was significantly
      increased, compared with healthy control (P<0.001). There was a positive linear
      correlation between the activity of NF-kappaB and the level of IL-8 in active
      stage of SRSNS, and a positive correlation trend was observed between the
      activity of NF-kappaB and the gene expression of respiratory tract viruses.
      CONCLUSION: Viral transactivation of transcription by NF-kappaB may be an
      important path for respiratory tract viruses triggering the pathogensis of SRSNS.

PMID- 16608071
TI  - [Prokaryotic expression and identification of human papillomavirus type 16 E7
      protein encoding gene].
AB  - OBJECTIVE: To construct the prokaryotic expression plasmid pET32/E7 and express
      the human papillomavirus type 16 E7 protein in E. coli. METHODS: HPV16 E7 gene
      was amplified by PCR. The amplified E7 fragment was inserted into the plasmid
      pET32a (+) that was digested with BamH I and Hind III. The recombinant plasmid
      pET32/E7 was transformed into E. coli JM109 which was selected with ampicillin.
      The positive clones containing recombinant plasmid pET32/E7 were verified by BamH
      I and Xho I digestion, and then sequenced. HPV16 E7-TRX recombinant protein
      expression in the E. coli BL21(ED3) was identified by SDS-PAGE and Western blot.
      RESULTS: The prokaryotic recombinant plasmid pET32/E7 was successfully
      constructed. The BL21(DE3) transformed recombinant plasmid pET32/E7 had expressed
      HPV16 E7-TRX recombinant protein effectively. Under the conditions of 1 mmol/L
      IPTG and 30 degrees C, the amount of HPV16 E7-TRX recombinant protein was about
      30% of bacterial total proteins. CONCLUSION: The construction of the prokaryotic
      recombinant plasmid pET32/E7 and the successful expression of the recombinant
      protein HPV16 E7-TRX would strongly promote the research of the biological
      properties and the transformational mechanism of the HPV16 E7 protein on the
      specific cells.

PMID- 16608072
TI  - [A preliminary study on the mechanism of neurotoxicity of MDMA--oxidative stress
      harm].
AB  - OBJECTIVE: Establishing a long-term neurotoxic model to explore the mechanism of
      neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) and the putative
      protection conferred by Vit C against oxidative stress harm. METHODS: Male Wistar
      rats were randomly assigned to control group (A) and MDMA treatment groups(B, C,
      D, E). Rats of group B were given MDMA 20 mg/kg; groups C, D, E were given Vit C
      250 mg/kg 30 min before administration of MDMA (Vit C 30 min group) and 3 h (Vit
      C 3 h group) and 5 h (VitC 5 h group) after administration of MDMA, respectively.
      Rats of control group were treated with the same volume of saline. Concentrations
      of ATP and ADP in brain cortex and 5-HT in hippocampus and occipital cortex were
      measured by high perfor-mance liquid chromatography; the expression of SERT mRNA
      was detected by in situ hybridization; and the expression of protein GFAP was
      detected by immunohisto-chemistry. RESULTS: hours after MDMA treatment, the
      concentration of ATP in brain cortex was lessened, compared with control (P
      <0.05). On the 7th day after MDMA treatment, the concentration of 5-HT in rat
      hippocampus and occipital cortex was decreased, compared with control (P<0.05).
      The expression of SERT mRNA in hippocampus was decreased, whereas the expression
      of GFAP in brain tissue was increased (P<0.05). The adminstration of Vit C 30 min
      before MDMA treatment and 3 h after MDMA treatment did not curb the decrease of
      ATP, 5-HT and the expression of SERT mRNA, but Vit C administrated 5 h after MDMA
      treatment could curb the decrease of ATP and the functional markers of 5-HT. And
      Vit C given at three time points did downregulate the GFAP expression.
      CONCLUSION: MDMA could deplete the direct energetic substance ATP. MDMA could
      exert neurotoxic effect on 5-HT system. Vit C given 5 h after MDMA administration
      could provide neuroprotection for ATP and 5-HT system.

PMID- 16608073
TI  - [Construction and expression of Neisseria surface protein (nspA) of Neisseria
      gonorrhoeae in Escherichia coli].
AB  - OBJECTIVE: To construct neisseria surface protein (NspA) recombinants of
      Neisseria gonorrhoeae from a reference strain and express this protein in E.
      coli. METHODS: The fragments of NspA gene of Neisseria gonorrhoeae was amplified
      by PCR from the reference strain genomic DNA and cloned into expression vector
      pET-30c (+) to get the pET-NspA recombinants. The recombinants were verified with
      restrictive endonuclease digestion and sequence analysis. The verified
      recombinant was transformed into E. coli BL21 (DE3). After inducing with IPTG,
      the expressed NspA protein was analyzed by SDS-PAGE and Western Blot. RESULTS:
      The pET-NspA expression recombinants for the reference strain of Neisseria
      gonorrhoeae were successfully constructed and the induced recombinant NspA
      protein was observed. CONCLUSION: The successful expression of the Neisseria
      gonorrhoeae NspA protein will be very helpful for the further research of its
      antigenicity and immunological activity, and for the construction of preventive
      vaccines on Neisseria gonorrhoeae infection.

PMID- 16608074
TI  - [Genetic polymorphisms of three loci and implication to forensic medicine].
AB  - OBJECTIVE: To obtain population genetic data of short tandem repeat (STR) locus
      D2S1327, D1S1390, and D11S2008 and to investigate the disparity of allelic
      frequency distributions among populations from different regions. METHODS: Blood
      samples of 300 unrelated individuals from Chengdu (Han), Bangkok (Thai) and Maint
      (Germany) were taken and analyzed with single PCR, polyacrylamide gel
      electrophoresis and silver staining. RESULTS: In the three loci, 9, 6, and 8
      alleles and 32,14, and 22 genotypes were found respectively. The observed
      heterozygosity of 79%-82%, 63.0%-74.3%, and 72.0%-74.3% and discrimination power
      of 87.8%-92.6%, 79.6%-82.5%, and 87.6%-89.0% were identified for the three loci
      respectively. The genotype distributions of the three loci in the three
      populations fitted well with Hardy-Weinberg equilibrium. There was no significant
      difference in allelic frequency distributions among the three populations.
      CONCLUSION: The methods described in this paper are easy to perform and have high
      sensitivities. The discrimination power and exclusion chances of these three loci
      are desirable for forensic analysis and application.

PMID- 16608075
TI  - [Expression of peroxisome proliferator-activated receptors Y changes with age in
      vascular smooth muscle cells of spontaneously hypertensive rat].
AB  - OBJECTIVE: In order to elucidate the relationship between PPAR-gamma and the
      development of hypertension, we detected the expression of peroxisome
      proliferator-activated receptors gamma (PPAR-gamma) in the vascular smooth muscle
      cells (VSMCs) and the VSMC proliferation of spontaneously hypertensive rats (SHR)
      at different ages. METHODS: The expression of PPAR-gamma in the intact vascular
      tissues of rats at different ages were detected by immunohistochemistry. Aortic
      VSMCs were cultured. PPAR-gamma mRNA in primary and low-passage cultured VSMCs of
      various ages were determined by RT-PCR, and proteins were evaluated by
      immunohistochemistry and age matched Western Blot. Age matched Wistar-Kyoto rats
      (WKY) were used as control. RESULTS: This experiment demonstrated that the
      expression of PPAR-gamma increased with age in the intact aorta tissues of SHR.
      The expression of PPAR-gamma did not continuously increase in 24w-old SHR when
      compared with that in 16w-old SHR. No difference between 4w-, 24w-old SHR and age
      matched WKY was observed, but the expression of PPAR-gamma was greater in 8w- and
      16w old SHR than in age matched WKY. In primary and low-passage cultured VSMCs,
      the expression of PPAR-gamma mRNA and protein increased with age both in SHR
      VSMCs and WKY VSMCs of 4w, 8w and 16w old, and no difference between 4w- and 24w
      old SHR and WKY was noted, but the expression of PPAR-gamma was higher in 8w- and
      16w-old SHR than in age matched WKY. PPAR-gamma expression in 24w-old SHR did not
      increase and it was equal to 16w-old SHR and 24w-old WKY. CONCLUSION: These datas
      on SHR suggest that the expression of PPAR-gamma changes with age and the
      development of high blood pressure. PPAR-gamma expression may play a compensatory
      role in hypertension, but this compensatory action is limited.

PMID- 16608076
TI  - [The change of mast cells and macrophages in the lung of rat with pulmonary
      hypertension].
AB  - OBJECTIVE: To investigate the change of mast cells and macrophages in lung tissue
      of rats with pulmonary hypertension (PH) and the effect of simvastatin on it.
      METHODS: Pulmonary hypertension was established as follow, a shunt between
      abdominal aorta and inferior vena cava was created in rats, 8 days later, the
      rats were injected with monocrotaline (60 mg/kg). Moreover, a subgroup of rats
      were given simvastatin 2 mg/ (kg x d). The mean pulmonary artery pressure (mPAP)
      and right ventricular weight were measured, and the ratio of right ventricle/left
      ventricle plus septum CRV/(LV+S)) was calculated. The LSAB method was used to
      stain anti-tryptase and ED1 in the lung tissue of the rats. RESULTS: In
      comparision with the control group, mPAP and RV/ (LV+S) of PH rats increased
      significantly (P<0.05). The RV/(LV+S) in simvastatin group was lower than that in
      PH rats (P<0.05). The amount of mast cells and macrophages in PH rats were more
      than that in control group (P<0.05). The amount of mast cells in simvastatin
      intervention group decreased in comparision with the PH group while the
      macrophages showed no difference in simvastatin group (P>0.05). CONCLUSION: Mast
      cells and macrophages may be involved in the development of PH and/or the lesion
      caused by PH accelerate the accumulation and activation of mast cell and
      macrophages. Simvastatin has a preventive effect on rat PH, it inhibits mast cell
      proliferation may be one of mechanism.

PMID- 16608077
TI  - [Cathepsin B expression and malignances and angiogenesis in gliomas].
AB  - OBJECTIVE: To test the expression of Cathepsin B (CB) protease in gliomas and to
      investigate its correlation with the malignance and angiogenesis of gliomas.
      METHODS: Immunochemistry technique of strept actividin-biotin complex (SABC) was
      used to identify the CB expression and to measure the microvessel density (MVD)
      in 47 gliomas samples and 5 normal human brain tissues from patients with
      spontaneous cerebral hemorrhage. RESULTS: No CB expression was detected in the
      normal brain tissues. The expression levels of CB in astrocytoma, anaplastoma,
      and glioblastoma were 30% (6/20 weak positive), 86.7% (3/15 weak and, 10/15
      moderate positive), and 100.0% (2/12 moderate and 10/12 strong positive),
      respectively. The malignances of gliomas increased with CB expression (r=0. 77,
      P<0.05). The MVD also increased with CB expression (r= 0.56, P<0. 05), with an
      average of 15.57 +/- 8.52, 22.50 +/- 14.42, 39.85 +/- 8.75 and 49.90 +/- 11.30
      for the negative, weak, moderate, and strong CB expression gliomas respectively.
      CONCLUSION: CB expression is positively correlated with the malignances and
      angiogenesis of gliomas. CB expression could be one of the indicators for the
      degree of malignances and invasion of gliomas.

PMID- 16608078
TI  - [Survivin expression in ovarian carcinoma].
AB  - OBJECTIVE: To explore the possible relationship between expression of survivin
      and molecular mechanisms in patients with ovarian carcinoma (OC). METHODS:
      Survivin expressions in normal ovaries (n= 10), ovarian bordline tumors (n = 21),
      and ovarian serous cystadenomas (n = 38) were investigated by means of
      immunohistochemistry. RESULTS: No survivin protein was expressed in normal
      ovaries. Survivin protein was found in cytoplasm and/or in nucleus of tumor cell.
      Survivin expression was revealed in 42.9% (9/21) of ovarian bordline tumors; no
      significant correlation was observed between survivin expression and pathologic
      types or CA125 values (P > 0.05). Survivin protein was found in 76.3% (29/38) of
      ovarian serous cystadenomas, displaying a significantly higher expression than
      that in bordline tumors (P < 0.05). Survivin expression was positively correlated
      with tumor stage, histological grade and lymphonode metastasis (P < 0.05),
      whereas it was not significantly correlated with CA125 values, volume of ascites,
      and presence/absence of tumor cells in ascites (P > 0.05). CONCLUSION: High
      expression of Survivin protein may be related with the differentiation and
      metastasis of epithelial ovarian carcinoma.

PMID- 16608079
TI  - [Relationship between the expression of fragile histidine (FHIT) and the
      development of vulvar carcinoma].
AB  - OBJECTIVE: To explore the relationship between the reduction of FHIT expression
      of fragile histidine (FHIT) and the development of vulvar carcinoma. METHODS: The
      expression of the FHIT product was detected by immunochemistry in the tissue
      samples of 20 normal vulvas, 22 vulvar intraepithelial neoplasias (VINs), and 60
      primary vulvar carcinomas. RESULTS: The expressive rates of FHIT protein in the
      squamous epithelium of normal vulvas, VIN I - II, VIN II, and noninvasive and
      invasive vulvar carcinoma were 100% (20/20), 72.7% (8/11), 45.5% (5/11), and
      21.7% (13/60) respectively (P<0.05). The expressive rates of FHIT protein in the
      well differentiated, intermediately differentiated and poorly differentiated
      invasive vulav carcinoma were 60.0% (9/15), 20.0% (3/15), and 3.3% (1/30)
      respectively (P<0.05). The expressive rate of the impaired FHIT protein in the
      invasive vulva carcinoma with lymphnode metastasis (10%) was lower than that
      without lymphnode metastasis (27.5%). CONCLUSION: Abnormal FHIT expression may
      play an important role in the progression of vulvar carcinoma. The expression of
      FHIT may provide important information for the prognosis of vulva carcinoma.

PMID- 16608080
TI  - [siRNA against survivin coupling with epirubicin enhances to induce breast cancer
      cell MCF-7 to apoptosis].
AB  - OBJECTIVE: To use the sequence-specific siRNA knocking down the expressions of
      Survivin gene and inducing breast cancer MCF-7 cell line to apoptosis, and to
      couple the siRNA with Survivin for investigating the effects of MCF-7 cell
      induced to apoptosis and the chemotherapy sensitivity of breast cancer cell
      treated to epirubicin. METHODS: The molecular cloning technique was applied to
      construct the eukaryotic expression vector of siRNA against Survivin, and
      lipofectamine 2000 was used to transfect MCF-7 cell. Survivin expressions were
      detected by semi-quantitive RT-PCR and immunohistochemical SABC methods. The
      effects of inducing MCF-7 cell apoptosis and enhanced chemotherapy sensitivity to
      epirubicin were assessed by TUNEL method. RESULTS: The sequence-specific siRNA
      can, effectively and specifically, knock the expressions of Survivin gene down at
      both mRNA and protein levels, in which the expression inhibition rates were 64.91
      and 79.72% respectively. After 48 h, 8.75% cells transfected with siRNA
      expression vector were induced to apoptosis; Coupling siRNA against Survivin with
      epirubicin can induce the cell apoptosis rate up to 24.21%. CONCLUSIONS: In the
      study, the siRNA against Survivin can, effectively and specifically, decrease the
      expressions of Survivin gene in MCF-7 cell; blocking the expressions of Survivin
      can, in certain degree, induce MCF-7 cell to apoptosis and enhance cell
      chemotherapy sensitivity to epirubicin significantly; Survivin RNAi has a great
      potential value in the gene therapy of breast cancer.

PMID- 16608081
TI  - [Comparison of the long term results between two conditioning regimens MCC and
      BuCy in chronic myelocytic leukemia after allogeneic stem cell transplantation].
AB  - OBJECTIVE: To observe and evaluate the long term survival of patients with
      chronic myelocytic leukemia transplanted with MCC and BuCy conditioning regimens.
      METHODS: Fourteen cases were treated with MCC regimen (Melphanlan 170 mg/m2 x d x
      1, MeCCNU 400 mg/m2 x d x 1, CTX 60 mg/kg x d x 2) and the median follow up time
      was 6 years; 16 cases were treated with BuCy regimen (Busulfan 4 mg/kg x d x 4,
      CTX 60 mg/kg x d x 2) and the median follow up time was 4 year. RESULTS: All the
      patients were engrafted successfully. 4 of 10 patients examined in MCC group
      showed mixed chimerism at day 100 after transplantation, whereas only 1 of 12
      patients examined in BuCy group showed mixed chimerism. All the patients became
      complete donor source later without any DLI. The 5-year disease-free survival
      rate was 71.4% for MCC group and 62.5% for BuCy group. The transplant related
      mortality and relapse rate were 21% and 7% for MCC group, whereas those were 25%
      and 12% for BuCy group, respectively. The regimen related toxicity was relatively
      lower in MCC group and the median duration of hospitalization was 39 days (25-55
      days) for patients with MCC regimen, and 55 days (39-90 days) for BuCy regimen.
      CONCLUSION: MCC regimen has a partial ablative effect on CML and the long term
      disease-free survival is the same as that of BuCy regimen. In regard to the cost
      effect efficacy, MCC regimen has a substantial advantage over BuCy regimen.

PMID- 16608082
TI  - [A study on expression of caspase-8 in organs of rats after electrical injury at
      antemortem or postmortem].
AB  - OBJECTIVE: This study was conducted to detect the expression of caspase-8 in
      organs of rats after The electrical injury so as to elucidate whether caspase-8
      is useful in identifying electrical lesion. METHODS: experiment included two
      parts. In the first part (the antemortem electrical injury part), thirty-five
      healthy male SD rats were randomly divided into seven groups (n = 5 per group),
      i. e. the group of rats subjected to instantaneous electrothanasia; the groups of
      rats subjected to cervical dislocation at 1 h, 2 h, 4 h, 8 h after electrical
      injury; the sham group and the normal control group. In the second part (the
      postmortem electrical injury part), twenty-five healthy male SD rats wererandomly
      divided into five groups (n=5 per group), i. e. the groups of rats electrically
      injured just after death, and at 15 min, 30 min, 60 min after death; and the
      postmortem sham group. All experimental rats were given respectively an electric
      shock with two metal clamps that were connected with two poles of 220 V
      alternating current by clamping the rats' left hind limbs and right forelimbs.
      The rats of sham group after death were clamped but not electrified. The brain,
      lung, heart, liver, spleen, kidney, the muscle of electrified limb, the cutis of
      electrified limb of all experimental rats and those organs of control groups were
      dissected to detect the expression of caspase-8 by immunohistochemistry staining,
      and the staining intensities were assessed by image analysis system. RESULTS: In
      the antemortem electrical injury groups, the expression of caspase-8 was positive
      in brain, heart, liver and kidney; the strongest staining intensity appeard at 4
      h after electrical injury and decreased at 8 h after electrical injury. In the
      group of rats electrically injuryed just after death, the expression of caspase-8
      was faint, and the expression of caspase-8 in spleen, lung, muscle and cutis was
      negative in the other groups. The expression of caspase-8 in all detected organs
      was negative in the other rats that were electrified after death. CONCLUSION:
      Caspase-8 can be regarded as an index in identifying electrical injury and
      distinguishing between antemortem and postmortem electrical injuryies.

PMID- 16608083
TI  - [Expression of tissue factor induced by IL-6 in HUVEC].
AB  - OBJECTIVE: To investigate the effects of IL-6 at the expression of tissue factor
      (TF) in human vein endothelial cells(HUVECs). METHODS: HUVECs were incubated with
      IL-6 at the concentration of 0.5 ng/mL. Cell viability was measured by CCK-8
      assay. The TF mRNA was detected by reverse transcript-polymerase chain
      reaction(RT-PCR) method. RESULTS: When HUVECs were exposed to IL-6 (0.5 ng/mL)
      within a period of 72 h, their viability did not decrease in comparison with the
      control; there was no statistical difference between the two groups. After the
      HUVECs were exposed to IL-6 (0.5 ng/mL) for 6 h, the TF mRNA level increased, and
      it reached the peak at 12 h; then it began to decline. The expression of TF mRNA
      induced by IL-6 was evidently detected from 6 h to 48 h. After the HUVECs were
      treated by IL-6 over 72 h, the expression of TF mRNA was no longer detected in
      HUVECs. CONCLUSION: IL-6 at the concentration of 0.5 ng/mL did not exert direct
      effect on cell viability. The increase of TF mRNA expression in HUVECs induced by
      IL-6 could play an important role in the modulation of blood coagulation disorder
      and in the mechanism related to coagulation system changes during

PMID- 16608084
TI  - [Serum IL-1 receptor antagonist and IL-1beta in patients with Graves'
      opthalmopathy].
AB  - OBJECTIVE: To investigate the mechanism of Graves' ophthalmopathy (GO) and the
      relationship between serum IL-1 ra and IL-1beta and the effectiveness of
      glucocoids in treating GO. METHODS: Serum IL-1ra and IL-1beta were measured by
      Enzyme linked immunosorbent assay (ELISA) and Radioimmunoassay (RIA) in three
      groups of people, which included 20 patients with severe GO (NOSPACES> or = IV),
      20 patients with Graves' disease (GD) without ophthalmopathy, and 20 healthy
      volunteers. Repeated measurements were undertaken in GO patients before and after
      glucocoids treatment to analyze the relationship between serum IL-1ra, and IL
      1beta and the effectiveness of glucocoids therapy. RESULTS: Before glucocoids
      therapy,GO patients had higher serum IL-1beta and lower IL-1ra/IL-1beta ratio.
      Glucocoids therapy increased serum IL-1ra and decreased IL-1beta, and thus
      increased the IL-1ra/IL-1beta ratio. CONCLUSION: Patients with GO have deficiency
      in IL-1ra synthesis. Glucocoids therapy can stimulate IL-1ra synthesis and
      inhibit IL-1beta synthesis.

PMID- 16608085
TI  - [Effect of captopril on pulmonary vascular remodeling induced by left-to-right
      shunt in rats].
AB  - OBJECTIVE: To investigate the therapeutic effect of angiotensin converting enzyme
      inhibitor on pulmonary vascular remodeling of pulmonary hypertension induced by
      high pulmonary blood flow. METHODS: An arterial-venous shunt was surgically
      created between abdominal aorta and inferior vena cava in the rat of all groups
      except the control group. Captopril was given to all of the rats. Six weeks after
      the operation,pulmonary artery systolic pressure (PASP), pulmonary artery
      diastolic pressure (PADP) and right ventricular systolic pressure (RVSP) were
      measured. The rats' hearts were weighted to calculate the ratio of right
      ventricle mass to left ventricle plus septum mass. Immunohistochemical stains
      were used to identify alpha-actin and PCNA distribution in pulmonary arteries.
      Morphometric parameters (vascular wall thickness and muscularization) were used
      to assess the remodeling of small pulmonary arteries. RESULTS: The PASP, PADP,
      RVSP, RV/(LV+S), RV/BW, and (LV + S)/BW of the rats in the shunt group were
      significantly greater than those of the control group. Muscularization of small
      pulmonary arteries and pulmonary artery medial hypertrophy (wall thickness) were
      evident in the shunt group. The proliferation index of the smooth muscle cells of
      the small and medium-sized pulmonary arteries was significantly higher and the
      alpha-actin IOD was significantly lower in the rats of the shunt group than those
      of the control. By contrast, the levels of PASP, PADP, RVSP, RV/(LV+S), RV/BW,
      (LV+ S)/BW, and muscularization were lower in the rats of captopril group than
      those of the control. CONCLUSIONS: Captopril slows down pulmonary hypertension
      and remodeling development. Captopril and losartan may have preventive and
      therapeutic effects on pulmonary hypertension induced by congenital left-to-right
      shunts.

PMID- 16608086
TI  - [Effect of dachuanxiongwan on the expression of vascular epithelial growth factor
      in rats with cerebral ischemia].
AB  - OBJECTIVE: To study the effect of Dachuanxiongwan on the expression of vascular
      epithelial growth factor in the rats after focal cerebral ischemia and
      reperfusion. METHODS: The ischemia and reperfusion model was established by
      blocking the middle cerebral artery of the rats with a nylon thread for two
      hours. Twenty male Sprague-Dawley rats with middle cerebral artery occlusion
      (MCAO) were randomly divided into two groups. One of the group of rats were
      administered with DCXW, 4.13 g/kg x d, twice a day for 3 days by gavaging, while
      other group were given the same volume of saline as a control. Seventy-two hours
      after reperfusion, the neuropathological function of the rats were evaluated
      according to Longa. The rats were then sacrificed and the samples of cerebrum
      were processed and embedded in paraffin and cut into sections. The expression of
      VEGF was determined by immunocytochemistry. RESULTS: The score of the
      neuropathological function of the DCXW treated group (1.5 +/- 0.71) was lower
      than that of the control group (2.3 +/- 0.82, P = 0.032). More VEGF-positive
      cells were found in the rats treated with DCXW than those in the control group (P
      = 0.000). CONCLUSION: DCXW upgrades the expression of VEGF and may have a
      positive effect on the cerebrum following ischemia and reperfusion.

PMID- 16608087
TI  - [Effect of dexamethasone on expression of fractalkine in lipopolysaccharide
      induced acute lung injury].
AB  - OBJECTIVE: To investigate the effect of dexamethasone on the expression of
      fractalkine (FKN) in lipopolysaccharide (LPS)-induced acute lung injury (ALI).
      METHODS: The rat model of ALI was established by injection of LPS at the dose of
      4 mg/kg. 42 Wistar rats were randomly divided into the normal group (n=6), LPS
      group (n=18), and dexamethasone (DEX) group (n = 18), and then the rats in both
      LPS and DEX groups were divided into three subgroups (1 h, 2 h and 4 h after
      injection of LPS), respectively. The pathological condition and the wet/dry ratio
      (W/D) of the lung were observed, and serum TNF-alpha level, and FKN mRNA of the
      lung were detected with ELISA and RT-PCR. RESULTS: The W/D, serum TNF-alpha
      level, and FKN mRNA of the lung were significantly increased in LPS group,
      compared with those in normal group (all P < 0.05), but the W/D, serum TNF-alpha
      level, and FKN mRNA of the lung in the DEX group were much more decreased than
      those in the LPS group (all P < 0.05). In addition, the expression of FKN mRNA in
      the lung tissue positively correlated with the concentration of TNF-alpha (r =
      0.674, P <0.05). CONCLUSION: The findings suggested that pre-treatment with
      dexamethasone could inhibit the TNF-alpha level and prevent the increase of the
      expression of FKN mRNA, which may be one of the mechanisms by which DEX serves as
      a protection against LPS-induced lung injury.

PMID- 16608088
TI  - [Effect of alveolar surgery-aided rapid orthodontic tooth movement on bone
      formation].
AB  - OBJECTIVE: To test the effect of alveolar surgery on orthodontic tooth movement
      and born remodeling. METHODS: Alveolar surgery was performed on one side
      (experimental side) whereas the traditional tooth movement was performed on the
      other side (control side) of the teeth in ten dogs. The treatments lasted for
      four weeks. The bone formation was evaluated using the vital bone marker
      tetracycline and immunohistochemistry 1, 2, 3, 4 and 8 weeks after the treatments
      respectively. RESULTS: In the total of the four weeks, the distal movement of
      experimental tooth was much faster (4.31 +/- 0.46 mm) than control tooth (2.16 +/
      0.42 mm), whereas the anchorage lost (0.44 +/- 0.07 mm) was the same with the
      control (0.46 +/- 0.09 mm). Compared to the control side, the tetracycline
      labeling lines were wider; the increase of the expression level of BMP-2 appeared
      earlier, greater and lasted longer in the tension area of the experimental side.
      CONCLUSION: Alveolar surgery could promote bone remodeling and accelerate the
      movement of orthodontic teeth.

PMID- 16608089
TI  - [Impact of flutamide on sex differentiation in rats].
AB  - OBJECTIVE: To investigate the adverse effect of flutamide on the sex
      differentiation of F1 generation male rats and to establish a rat model of
      hypospadis. METHODS: Sixty pregnant SD rats were divided randomly into one
      control group and five treatment groups. Flutamide was injected subcutaneously
      (sc) with normal salin (NS) at a dose of 0, 4882.8, 5078.1, 5273.4, 5468.7, and
      6250.0 microg/kg x d to the rats in the above groups respectively during the
      period of gestation day (GD) 12 to 17. The fetuses of two rats from each group
      were anatomized on GD18 to extract genital tubercle (GT) to make pathological
      sections. Meanwhile, the position of testes and the development of prostates were
      examined. The position of urethral opening and testes were examined on GD2, 13
      and 28. RESULTS: The incidence of hypospadias increased with the dose of
      flutamide (0, 29.00%, 40.00%, 63.68%, 78.72%, and 100% for the above groups
      respectively). The incidence of single cryptorchidism also increased with the
      dose of flutamide (0, 4.23%, 6.23%, 9.23%, 11.52%, and 16.28% for the above
      groups respectively). Flutamide led to 100% incidence of prostate agenesis,100%
      incidence of female-like areola of nipple, and 100% incidence of female-like
      anogenital distance (AGD). CONCLUSION: Flutamide can cause abnormal sex
      differentiation and sex development and induce the experimental model of
      hypospaias in rats.

PMID- 16608090
TI  - [Establishment of a cisplatin-multidrug resistance cell line of human
      osteosarcoma].
AB  - OBJECTIVE: To establish a multidrug resistance cell line of human osteosarcoma
      from the MG63 cell line and to test its attributes. METHODS: The human
      osteosarcoma MG63 cells were exposed to high and gradually increased dose of
      cisplatin for 186 days to introduce its multidrug resistance (MG63/R). The
      sensitivity of the multidrug resistance was measured by MTT assay. The morphology
      and ultramicrostructure of the cells were observed using optical microscopy and
      transmission electron microscopy. The proliferation ability of the cells was
      measured by growth curve and colony-forming assay. The cell cycle and apoptosis
      and the expression of P-pg, bcl-2, P53 in the MG63 and MG63/R cell lines were
      analyzed by flow cytometry. RESULTS: The resistance index of the MG63/R cells to
      cisplatin was 83.557 +/- 4.841. The cells also had resistance to doxorubicin,
      vincristin, methotrexate and cyclophosphamide. Disordered structure of the MG63/R
      cells was observed through microscopy. The cells appeared in triangle, polygon
      and polynucleation. The increase of granular endoplasmic reticulums and apophyses
      was observed through transmission electron microscopy. The proliferation ability
      of MG63/R increased significantly, with a low apoptosis index. Compared to the
      MG63, the expressions of P-pg and bcl-2 in the MG63/ R increased while the
      expression of P53 decreased. CONCLUSION: A multidrug resistance cell line
      (MG63/R) of human osteosarcoma is established, which will benefit to further
      studies as a new experimental model.

PMID- 16608091
TI  - [Investigating the fluoroquinolone molecular resistant mechanism of
      Stenotrophomonas maltophilia].
AB  - OBJECTIVE: To research DNA gyrase and topoisomerase IV quinolone resistance
      determining regions (QRDRs) in Stenotrophomonas maltophilia clinical isolates
      with different resistant levels of quinolone susceptibility. METHODS: We selected
      five strains for which the MIC of ciprofloxacin were higher than 2 mg/L and were
      negative for efflux mechanism; then we amplified their QRDRs of gyrA and parE,
      purified the fragment, and analyzed the nucleotide sequences. RESULTS: In
      Stenotrophomonas maltophilia DNA gyrA, the changes at positions 83 and 87
      commonly involved in quinolones resistance in gram-negative bacteria were absent,
      and there was Gln but not Ser or Thr. Of the five strains, one strain showed a
      ParE amino acid change in position 402, the other was in position 432, but the
      mutations were not associated with FQNS resistance. CONCLUSION: FQNS resistance
      in Stenotrophomonas maltophilia is related to active efflux pump and may be
      correlated with a low level of permeability. But it is not clear whether the
      resistance is related to the mutants in DNA gyrase and topoisomerase N.

PMID- 16608092
TI  - [A comparative study on the resistance of bacteriophage T4, phiXM174D, and f2 to
      glutaraldehyde in laboratory].
AB  - OBJECTIVE: To identify the best indicative bacteriophage in disinfection tests
      through comparing the resistance of bacteriophage T4, phiX174D, and f2 to
      glutaraldehyde. METHODS: The virucidal activities of glutaraldehyde against
      bacteriophage T4, phiX174D, and f2 were assessed with suspension tests along with
      neutralizer tests. The double-agar-layer plaque technique was used to detect the
      bacteriophage T4, phiX174D, and f2. RESULTS: (1)In a condition of 3000 mg/L of
      glutaraldehyde and 20 minutes of contact or 6000 mg/L of glutaraldehyde and 5
      minutes of contact, "disinfection" level for bacteriophage T4 was achieved, with
      the log10 inactivation value (LIV) or log10o reduction value (LRV) (=log10No
      log10Nt) > or = 4. 00 log10. (2) In a condition of 2500 mg/L of glutaraldehyde
      and 20 minutes of contact or 5000 mg/L of glutaraldehyde and 5 minutes of
      contact, the LIV for bacteriophage phiX174D reached "disinfection" level; (3) In
      a condition of 4000 mg/L of glutaraldehyde and 40 minutes of contact or 8000 mg/L
      of glutaraldehyde and 10 minutes of contact, the LIV for bacteriophage f2 reached
      "disinfection" level. CONCLUSION: Bacteriophage f2 and bacteriophage phiX174D has
      the strongest and weakest resistance to glutaraldehyde respectively.

PMID- 16608093
TI  - [A study of correlation between the blood supply types of PHcc on spiral CT and
      the level of VEGF expression in PHcc].
AB  - OBJECTIVE: To study the correlation between the blood supply types of primary
      hepatocellar carcinoma (PHcc) on Spiral CT and the level of vascular endothelial
      growth factor (VEGF) expression in PHcc for improvement in treatment strategies
      and prognostication. METHODS: Forty-five cases of PHcc identified by operation
      and pathology were investigated. Immunohistochemistry staining in SP was
      performed. The relationships between blood supply types of PHcc on Spiral CT
      during dual-phase scanning and the expression levels of VEGF in well
      differentiated, moderately differentiated and poorly differentiated PHcc were
      analyzed. RESULTS: There were four blood supply types of PHcc on Spiral CT. Both
      the strong positive staining and the positive staining were most frequently seen
      in the hepatic artery blood supply type, and then were frequently in the double
      blood supply type, i. e. the hepatic arterial supply combining with the portal
      blood supply type. The positive staining results were rarely seen in the portal
      blood supply type and poor blood supply type (P<0.001). And with the escalation
      of the Edmonson- Steiner histological grades, the VEGF expression levels were
      shown to increase correspondingly (P < 0.05). CONCLUSION: We can ascertain the
      blood supply type of PHcc and infer the VEGF expression levels that reflect the
      PHcc angiogenesis condition and the histological grades by means of Spiral CT
      during dual- phase scanning. Hence this method is useful for the selection of
      PHcc treatment plans, including anti-angiogenesis and evaluating the prognosis.

PMID- 16608094
TI  - [Production and identification of monoclonal antibody against N terminal of
      AIB1].
AB  - OBJECTIVE: To make and identify the monoclonal antibody against AIB1-N. METHODS:
      BALB/c mice were immunized with purified GST-AIB1-N protein, McAb against AIB1-N
      was produced by hybridoma technique. ELISA and Western-blot were used to identify
      the immunoglobin subtype and specificity. Results A hybridoma cell was
      successfully produced to secrete the McAb against AIB1-N, which was identified to
      belong in IgG1 subtype. By western-blot, the McAb against AIB1 displayed strongly
      specificity and high affinity. CONCLUSION: The McAb against AIB1 protein may be a
      useful tool for studying the biological properties of AIB1 expression and the
      clinical laboratory detection.

PMID- 16608095
TI  - [Occupational stress and job burnout in doctors].
AB  - OBJECTIVE: To investigate the status of job burnout in doctors and its
      relationship with occupational stress. METHODS: A total of 561 doctors from three
      provincial hospitals were randomly selected. The Maslach Burnout Inventory
      General Survey (MBI-GS) was used to identify job burnout. The occupation stress
      inventory revised edition (OSI-R) was used to evaluate the level of occupational
      stress. RESULTS: Surgeon and doctors working in the internal medicine wards
      scored significantly higher in job burnout than their colleagues (P < 0.05). The
      30-40 years of age group scored highest in exhaustion. The score of professional
      efficacy decreased with age and increased with educational levels. Role overload,
      responsibility, physical environment, reaction and self-care were major
      predictors for exhaustion. Role insufficiency, role overload and responsibility
      were major predictors for cynicism. Role insufficiency, social support and
      rational/cognitive were major predictors for professional efficacy. CONCLUSION:
      Maintaining moderate professional duty and responsibility, clearly defining job
      requirements, enriching leisure activities, and improving self-care ability are
      important measures to preventing job burnout.

PMID- 16608096
TI  - [Evaluating training programs on occupational health and safety: questionnaire
      development].
AB  - OBJECTIVE: To develop a questionnaire to evaluate the quality of training
      programs on occupational health and safety. METHODS: A questionnaire comprising
      five subscales and 21 items was developed. The reliability and validity of the
      questionnaire was tested. Final validation of the questionnaire was undertaken in
      700 workers in an oil refining company. RESULTS: The Cronbach's alpha
      coefficients of the five subscales ranged from 0.6194 to 0.6611. The subscale
      scale Pearson correlation coefficients ranged from 0.568 to 0.834 . The theta
      coefficients of the five subscales were greater than 0.7. The factor loadings of
      the five subscales in the principal component analysis ranged from 0.731 to
      0.855. Use of the questionnaire in the 700 workers produced a good
      discriminability, with excellent, good, fair and poor comprising 22.2%, 31.2%,
      32.4% and 14.1 respectively. Given the fact that 18.7% of workers had never been
      trained and 29.7% of workers got one-off training only, the training program
      scored an average of 57.2. CONCLUSION: The questionnaire is suitable to be used
      in evaluating the quality of training programs on occupational health and safety.
      The oil refining company needs to improve training for their workers on
      occupational health and safety.

PMID- 16608097
TI  - [Association of the behavior problems of school-age children with gender, age and
      registered permanent residence].
AB  - OBJECTIVE: To assess whether and how the prevalence of behavior problems among
      the school-age children are associated with their gender, age and registered
      permanent residence. METHODS: The behavior problems in 2156 children were
      estimated with the aid of Rutter Parent Questionnaire (RA2) and Rutter Teacher
      Questionnaire (RB2) from September to October 2004. RESULTS: The prevalence rates
      of children having behavior problems were 13.5% in RA2 and 13.8% in RB2, and
      these were higher in boys than in girls (RA2:1.79; RB2: 2.82). According to
      parents' and teachers' assessments, the highest positive rates in grades were
      16.3% in grade 2 and 15.1% in grade 4, and the highest positive rates among the
      three groups of permanent residence were 16.3% in rural children and 19.5% in
      urban pupils. In multivariate logistic regression analyses, the significant
      positive correlates were male, urban for antisocial behavior and male for
      neurotic behavior in RA2, and male, urban and higher grade for all behavior
      problems in RB2. CONCLUSION: The detected rate of behavior problems among school
      age children in Zhejiang province was higher than that reported by other
      researchers. The differences of gender, age, and registered permanent residence
      were significant in both RA2 and RB2. Male, urban and higher grade children
      should be an important group of school-age children in need of guidance with
      mental health.

PMID- 16608098
TI  - [Estrogenic effects of gasoline-fueled vehicle exhausts and methanol-fueled
      vehicle exhausts].
AB  - OBJECTIVE: To investigate the estrogenic effects of gasoline-fueled vehicle
      exhausts and methanol-fueled vehicle exhausts and provide a scientific basis for
      replacement of gasoline by methanol as fuel in vehicle. METHODS: The estrogen
      like activities of gasoline-fueled vehicle exhausts and methanol-fueled vehicle
      exhausts were detected using the recombinant yeast estrogen system. RESULTS: The
      A600 value of gasoline-fueled vehicle exhausts was 0. 081 when the concentration
      of gasoline-fueled vehicle exhausts was 1000 mL/mL, and there were significantly
      statistical differences as compared with those of the dimethyl sulfoxide (DMSO)
      control group (P < 0.05), which indicated that such concentration had poisonous
      effects on yeast cell; when the concentration of gasoline-fueled vehicle exhausts
      was 31.25 mL/mL, the estrogen-like activities of gasoline-fueled vehicle exhausts
      could be detected, and there were significantly statistical differences as
      compared with those of the DMSO control group (P<0.05). Besides, the estrogen
      like activities could not be detected in other groups with various
      concentrations. The estrogen-like activities of methanol-fueled vehicle exhausts
      could not be detected, and there were no significantly statistical differences in
      A600 value (P > 0.05) when each group was compared with the DMSO control group.
      CONCLUSION: Gasoline-fueled vehicle exhausts have weak estrogenic effects,
      whereas methanol-fueled vehicle exhausts have no such effects.

PMID- 16608099
TI  - [Impact of mesorectal involvement on the outcome of patients with rectal cancer].
AB  - OBJECTIVE: To assess the relationship between the incidence and prognostic
      significance of mesorectal involvement. METHODS: 328 cases of rectal cancer
      resected with total or subtotal mesorectal excision in our hospital from Jan.
      1997 to Dec. 1998 were followed up and analyzed in this study. The neoplastic
      foci were identified at the pathologic examination of the mesorectum. RESULTS:
      Neoplastic mesorectal metastasis was found in 234 cases (71.3%); node involvement
      in 59.8% and microscopic foci involvement in 36% of all cases (isolated in 11.6%,
      microfoci alone without any kind of other mesorectal involvement). Microscopic
      deposits were found in 10.3% of TNM Stage I tumors, in 18.4% of Stage II and in
      45.1% of Stage III cancers. Five-year disease-free survival rate (49.6% vs.
      91.4%) were observed in patients with mesorectal involvement, compared with those
      without deposits. CONCLUSION: The incidence of neoplastic foci in the mesorectum
      seem to affect prognosis, even in early staged tumors. The presence of mesorectal
      foci should be considered an index in modifying the conventional staging of the
      rectal tumor.

PMID- 16608100
TI  - [Study on the preparation of plasmid DNA-containing liposomes and their
      properties].
AB  - OBJECTIVE: To prepare plasmid DNA-containing liposomes using detergent removal
      method and investigate the properties of liposomes. METHODS: Using soybean
      phospholipid and DDAB as lipid materials and Myrj53 as surface modified material,
      we prepared liposomes by means of detergent removal technique. The shape, size
      and zeta potential of the liposomes were characterized by TEM and laser particle
      size analyzer, respectively. The encapsulation efficiency was also investigated.
      The ability of liposomes to protect the plasmid DNA from degradation was
      investigated through incubation with DNase I for different time. RESULTS: The
      liposomes were relatively and regularly spherical in shape and had an average
      size of 72.73 +/- 7.14 (n = 3) nm with the polydispersity index of 0.288+/-0.093
      (n = 3). The zeta potential of the liposomes was -23.77+/- 3.51 (n = 3) mV. The
      encapsulation efficiency of DNA reached 88.13% +/- 4.41% (n = 3). Liposomes could
      provide DNA with enough protection from degradation by DNase I . CONCLUSION:
      Detergent removal method is effective and practicable for preparing small-sized
      plasmid DNA-containing liposomes.

PMID- 16608101
TI  - [Isolation and purification of BMScs of GFP transgenic mouse using the method of
      adhering to cuture plastic in different time].
AB  - OBJECTIVE: To adopt the method of adhering to culture plastic in different time
      for cultivating and purifying BMSCs of green fluorescent protein (GFP) transgenic
      mice. METHODS: Bone marrow cells isolated from GFP transgenic mice are directly
      planted in culture flask and an exchange of the total volume medium is made at
      different time. Then the cells adhering to culture plastic are differently
      counted according to the cell types and are examined by immunohistochemistry
      using the antibodies of CD44, CD45 and CD54 in three days. Moreover, the cells
      after the exchange of the total volume medium in 4 hours, 8 hours and 24 hours
      are selected and successively subcultured down to the fifth passage. Then the
      result of amplification is calculated and the cells are examined by
      immunohistochemistry using the antibodies of CD44, CD45 and CD54. RESULTS: With
      the extending of the time for the first exchange of medium, the density of cells
      adhering to culture plastic increased accordingly, but the BMSCs proportion
      decreased. The cells after first exchange of medium in 4 hours had high BMSCs
      proportion but low BMSCs density, and the cells in 24 hours had high BMSCs
      density and low BMSCs proportion. However, the cells in 8-10 hours had high BMSCs
      density and also high BMSCs proportion. The subcultured BMSCs could stably
      express GFP. CONCLUSION: The method of adhering to culture plastic in different
      time for cultivating and purifying BMSCs of GFP transgenic mice is effective. It
      is suitable to make the first exchange of total volume medium in 8-10 hours. The
      subcultured cell has the capacity for amplification and will probably be a seed
      cell for the research of tissue engineering and gene therapy.

PMID- 16608102
TI  - [Determination of trace thallium by platform-GFAAS after preconcentration with
      polyurethane foam].
AB  - OBJECTIVE: To develop a method for trace thallium determination. METHODS:
      Thallium (L) was oxidized to thallium (III) by bromine water and the thallium
      (III) was complexed to [TlCl4]- in 20 mL/100 mL HCI and absorbed by polyurethane
      foam. The adsorbed thallium was eluted by a boiling water bath and determined by
      platform-GFAAS. Tl (III) could be analyzed directly and the total Tl be analyzed
      after oxidation, so speciation could be achieved. RESULTS: In the range of 5-100
      ng/mL the linear equation was y = 0.013x + 0. 012 with the regression coefficient
      0.996. The relative standard deviation was 4.7% for the standard solution of 5.00
      ng/mL and the recoveries of water samples were in the range of 95.7%-104.5%.
      CONCLUSION: The proposed method could determine trace thallium as low as 0.02
      ng/mL.

PMID- 16608103
TI  - [Experimental study of pristane-induced murine lupus model].
AB  - OBJECTIVE: To establish a mouse model of systemic lupus erythematosus(SLE) and to
      discuss the role of environmental factors in the pathogenesis of SLE. METHODS:
      Thirty 10-week-old female BALB/c mice were divided into the model group and
      control group. The model mice received a single intraperitoneal injection of 0. 5
      mL of pristane, while control mice received a single i.p. injection of 0. 5 mL of
      0.9% NS. Autoantibodies and proteinuria were detected before injection and
      monthly thereafter. 8 months after injection, all mice were bled to death.
      Kidneys were excised to observe the histopathologic evidence of
      glomerulonephritis. RESULTS: After pristane injection, antinuclear antibody(ANA)
      and anti-dsDNA antibody appeared in sera as early as 3 months and 4 months
      respectively. At 8 months, the incidence rates of ANA and anti-dsDNA antibody
      were 87.5% and 47.8% respectively. The protein concentration of urine in most
      mice was > or =1+ (300 mg/L). Light microscopy and immunofluorescence of kidney
      sections indicated glomerulonephritis. In control group, only one serum was ANA
      low-titer positive and another was anti-dsDNA antibody low-titer positive. The
      protein concentration of urine was < or = 1+. The histopathology and
      immunofluorescence showed no evidence of glomerulonephritis. Spearman correlation
      analysis indicated that anti-dsDNA antibody was correlated with proteinuria (r =
      0.538, P = 0.003). CONCLUSION: The murine lupus model can be successfully
      established in female BALB/c mouse with a single i. p. injection of 0. 5 mL of
      pristane and the specific autoantibody anti-dsDNA for SLE has appeared in sera of
      BALB/c mice.

PMID- 16608104
TI  - [Hypochondria circumscripta (to the problem of coenesthesiopathic paranoia)].
AB  - Hypochondria circumscripta manifests in patients with paranoial personality and
      signs of somatopsychic accentuation. A sample included 11 patients (6 men, 5
      women, mean age 54 years) who referred to dermatologists or had been admitted to
      gastroenterological and psychiatric units. Pathokinesis of hypochondria
      circumscripta comprises three stages: idiopathic algias, overmastering sensations
      and possession of pain. In the latter stage, delusional behavior targeted to the
      elimination of a part of the body, which is perceived as the source of pain,
      develops. Psychopathological disorders are realized in limits of
      coenesthesiopathic spectrum without tendency to interpretive delusion
      manifestation as well as transformation to systematic delusion of persecution
      during the disease course. As a consequence of above mentioned peculiarities of
      psychopathological structure, the stage of possession of pain may be designated
      as coenesthesiopathic paranoia. Because of the small sample, the findings can be
      considered as preliminary ones.

PMID- 16608105
TI  - [Lambert-Eatone myastenic syndrome].
AB  - A detailed comparative analysis of neurologic symptoms in 45 patients with
      Lambert-Eatone myastenic syndrome (LEMS) and 42 patients with generalized
      myasthenia allowed us to single out clinical patterns facilitating disease
      diagnosis and differentiation. There were no clinical differences in patients
      having LEMS with or without paraneoplastic process. Electromyography study
      revealed the presence of typical phenomena: a reduced amplitude of compound
      muscle action potential and incremental response at 40-Hz stimulation. The
      compound muscle action potential tripled after 20 s of maximal voluntary
      contraction. Sera from 89% of patients with LEMS contained IgG antibodies that
      immunoprecipitate a radiolabeled complex of a selective antagonist of P/Q type
      voltage-gated calcium channels. The degree of inhibition of calcium influx by
      patient's IgG correlated with the reduction in amplitude of the resting compound
      muscle action potential.

PMID- 16608106
TI  - [The interferon beta therapy after the first clinical episode of demyelination in
      multiple sclerosis].
AB  - The currently available treatment of definite multiple sclerosis (MS) includes
      different preparations of interferon beta. Recently reported data of
      pathomorphological, MRI, MR-spectroscopy and immunohistochemical studies suggest
      that axonal damage secondary to inflammation appears at the very early stage of
      MS. Early pathological events can predict a future course of the disease.
      Inflammatory activity in relapsing MS does not confine to episodes of clinical
      impairment but often develops before the first episode and generally continues
      during remissions. Patients with clinically isolated syndrome (CIS) and an
      abnormal brain MRI scan are at high risk of developing clinically definite MS
      (CDMS). If the presence of lesions predisposes to MS, the number of lesions
      determines when disability will develop. The results of interferon beta trials in
      patients with CIS showed significant benefit of the treatment in decreasing risk
      of CDMS development.

PMID- 16608107
TI  - [Coaxil (tianeptine) in the treatment of depression in Parkinson's disease].
AB  - Clinical evaluation of tianeptine (coaxil) efficacy and safety has been conducted
      in an open non-comparison study of 18 patients with Parkinson's disease (PD) with
      moderate and marked depressive symptoms measured by Hamilton and Beck depression
      scales. To the end of the 3rd month of the treatment, scores on the Hamilton
      Depression Scale (HAM-D) decreased by 34% and by 31% on the Beck Depression Scale
      (p<0.05) as compared to the baseline level. Improvement was observed in 14 out of
      18 patients (77%), with decreasing of HAM-D scores by 50% and over in 8 patients
      (44%). An analysis of depressive symptoms structure revealed that the improvement
      was due to the decrease of anxiety and somatoform symptoms and, to a lesser
      extent, to melancholy and sleep disorders. However, a level of apathy did not
      change. The decrease of depression was accompanied by significant improvement of
      quality of life. The efficacy of coaxil was higher in patients with less marked
      depressive and motor symptoms, shorter disease course and less cognitive
      impairment. Good tolerability of coaxil was observed during the whole study.
      Therefore, coaxil may be recommended for treatment of depressive symptoms in
      patients with PD.

PMID- 16608108
TI  - [Use of reminyl (galantamine) in the treatment of dementia].
AB  - Clinical efficacy and safety of reminyl monotherapy has been studied in patients
      with dementia of Alzheimer's and mixed vascular-degenerative types. The reminyl
      treatment has been conducted in dosage of 16 mg/kg daily during 6 months in 30
      patients (20 female, 10 male) aged from 59 to 86 years. The results of the study
      revealed high efficacy of reminyl in the treatment of patients with mild and
      moderate dementia and good tolerability of the medication.

PMID- 16608109
TI  - [Prognosis of remote consequences of combat mental trauma using logical
      statistical methods].
AB  - Prognosis of remote consequences of acute stress disorders and adaptation
      disorders as posttraumatic stress disorders (PTSD) is possible using relevant
      mathematical methods. The authors have used the following logical statistical
      methods: algorithms for search and statistical verification of optimal
      fragmentation of variables in multi-dimensional space ("Q-nearest neighbors",
      "statistically weighed syndromes") as well as a program of searching for multiple
      conjunctions of variables that allowed to single out statistically significant
      combinations of variables (p<0,001) and to divide the sample into two groups:
      with favorable and with unfavorable outcome both at the acute and remote stages
      of mental trauma. Predictors of unfavorable outcome found in the acute period of
      mental trauma were as follows: affective tension, impulsivity, high personal
      anxiety and depressive tendencies with reduced activity. Comparing to clinical
      evaluation, subjective criteria of mental state (self-rating) retained its
      informativeness for prognosis of protracted PTSD types. Using this set of
      variables, it became possible to predictt remote consequences (2-4 years) of
      psychogenias of combat situation with reliability of recognition of 85% for the
      favorable outcome and 79% for cases of protracted types.

PMID- 16608110
TI  - [Objective EEG correlates of deprivation in hypnosis-modulated catalepsy].
AB  - EEG was registered in healthy volunteers before and after their entry into
      modeling (hypnotic) catalepsy. The brain activity recorded under standard
      electrode placement (the 10-20 international classification) was processed using
      a special computer program. The data obtained were digitally represented as sets
      of standard parameters of EEG patterns in 0,5-32 Hz diapason (alpha-, beta1-,
      beta2,-, theta-, delta-rythms). These parameters were compared under different
      functional tests particularly connected with the control of sensomotor brain
      activity. Calculated coefficients of interhemisphere asymmetry allow one to
      evaluate dynamics of neuropsychological processes of deprivating adaptation
      related to low-frequency bands. EEG-parameters precisely evaluating the level of
      hypnotic catalepsy have been established.

PMID- 16608111
TI  - [Clinical polymorphism of neuroborreliosis at a late stage of the disease].

PMID- 16608112
TI  - [Phenotropil in the treatment of vascular encephalopathy].

PMID- 16608113
TI  - [Individual profile of functional asymmetry and psychosomatic disturbances in
      gastroenterological diseases].

PMID- 16608114
TI  - [Efficacy of donormil in the treatment of insomnia in patients with vascular
      encephalopathy].

PMID- 16608115
TI  - [Some peculiarities of clinical signs and treatment of alcoholic psychosis in
      women].

PMID- 16608116
TI  - [Neurological aspects of the diseases of N.N. Miklukho-Maklai].

PMID- 16608117
TI  - [A current conception of the pathogenesis of trigeminal neuralgia].

PMID- 16608118
TI  - [Chromosome abnormalities in schizophrenia].

PMID- 16608119
TI  - Functions of the HIV-1 matrix protein p17.
AB  - HIV-1 replication is a dynamic process influenced by a combination of viral and
      host factors. The HIV-1 matrix protein p17 is a structural protein critically
      involved in most stages of the life cycle of the retrovirus. It participates in
      the early stages of virus replication as well as in RNA targeting to the plasma
      membrane, incorporation of the envelope into virions and particle assembly.
      Besides its well established functions, p17 acts as a viral cytokine that works
      on preactivated--but not on resting--human T cells promoting proliferation,
      proinflammatory cytokines release and HIV-1 replication after binding to a
      cellular receptor (p17R). Thus, p17 might play a key role in the complex network
      of host- and virus-derived stimulatory factors contributing to create a
      favourable environment for HIV-1 infection and replication. Here, we present a
      brief overview of the functions played by the matrix protein p17 in the HIV-1
      life cycle and summarize the current understanding of how p17 could contribute to
      the pathogenesis of HIV-1 disease.

PMID- 16608120
TI  - A novel assay to detect low-titred antibodies to interferon beta in multiple
      sclerosis patients.
AB  - Neutralizing antibodies (NAbs) may compromise interferon (IFN) clinical efficacy
      in patients with multiple sclerosis (MS) receiving IFN-beta treatment. When
      bioassays are used for anti-IFN-beta antibody detection, they are unable to
      discriminate between NAbs or other interfering substances with anti-IFN activity.
      Here we report the development of an anti-IFN-beta Western blot method that
      facilitates the detection of IFN low-titred antibodies and characterizes such low
      neutralizing activity as specifically due to the presence of particular IFN
      antibodies. The assay was characterized using serum samples from patients with MS
      treated with IFN-beta. It was developed by adding anti-IFN-positive antibody sera
      to Dynabeads M-280 tosylactivated followed by Western blot analysis. All sera
      samples from MS patients with IFN-betala NAbs (< or = 50 t1/10) proved to be
      antibody-positive using this new method and, more importantly, four of 27 binding
      antibody-negative sera samples were scored as IFN antibody-positive. The method
      was found to be rapid, specific and sensitive and consistent with respect to well
      established antiviral neutralization or commercial enzyme-linked immunosorbent
      assays.

PMID- 16608121
TI  - Expression of bioactive recombinant bovine interferon-gamma using baculovirus.
AB  - The precise role of bovine interferon-gamma (BoIFN-gamma) in disease and therapy
      is still poorly defined. Clearly it is involved in defence against parasites,
      bacteria, viruses and possibly tumor cells. This paper reports the expression of
      BoIFN-gamma in a baculovirus system to generate a fully functional recombinant
      protein. Bovine interferon-gamma cDNA was cloned from mitogen stimulated
      peripheral blood mononuclear cell (PBMC) RNA utilizing the reverse transcription
      polymerase chain reaction (RT-PCR). The cDNA open reading frame (ORF) encoding
      for a putative 166 amino acid protein (22KDa) was cloned and expressed into
      baculovirus transfer vector pBlueBac 4.5/V5 His. This vector was co-transfected
      with Autografa californica multiple nuclear polyhedrosis virus (AcMNPV) DNA into
      Spodoptera frugiperda cells (Sf9) and the recombinant virus, named AcBoIFN-gamma,
      was then recovered. Recombinant BoIFN-gamma (rBoIFN-gamma His) was accumulated in
      the serum-free medium of AcBoIFN-gamma-infected cells. The nickel affinity spin
      column purified rBoIFN-gamma His was shown to be a glycosylated 20-22 KDa protein
      as confirmed by SDS-PAGE glycan determination and showed antiviral activity in
      vitro against the bovine viral diarrhoea-mucosal disease virus (BVD/MD). The
      production of this bioactive rBoIFN-gamma His will allow us to explore this
      cytokine as a potential vaccine adjuvant or therapeutic agent for bovine
      diseases.

PMID- 16608122
TI  - Head and neck squamous cell carcinoma: role of the human papillomavirus in tumour
      progression.
AB  - High risk human papilloma viruses (HPVs) have been shown to be independent risk
      factors for anogenital tract cancers, and have also been detected in head and
      neck squamous cell carcinomas (HNSCC). The aim of our study was to determine the
      prevalence of HPV DNA in a group of 47 squamous cell carcinomas of the oropharynx
      and the oral cavity, and to compare the clinical behaviour of HPV positive and
      negative tumours. We also assessed the proliferation index, as evaluated by Ki67
      immunohistochemistry positivity, and the level of p53 reactivity. HPV DNA was
      found in 50% of carcinomas of the oropharynx and 36% in those of the oral cavity,
      the only genotype detected being HPV 16. Patients with HPV-positive carcinomas
      had a better overall survival than those with HPV-negative carcinomas. Our data
      suggest that HPV-positive oropharyngeal cancers comprise a distinct disease
      entity with an improved prognosis.

PMID- 16608123
TI  - Four year incidence of respiratory syncytial virus infection in infants and young
      children referred to emergency departments for lower respiratory tract diseases
      in Italy: the "Osservatorio VRS" Study (2000-2004).
AB  - Respiratory Syncytial Virus (RSV) is a frequent cause of hospital admission in
      young children and high risk babies such as premature newborns, or babies with
      underlying cardiac or pulmonary disease, or immunodeficiency. Outbreaks occur
      most frequently in the cold season in areas with temperate and Mediterranean
      climates. Aim of the "Osservatorio VRS" Study was to describe the time-related
      pattern of RSV epidemics in Italy, across four consecutive epidemics, from 2000
      to 2004. Nasal specimens for RSV detection were obtained and tested by an
      immunoenzymatic test. A total of 2110 children were tested for RSV determination,
      the rate of children with RSV infection was 21%, and that of children
      hospitalized for RSV disease was 49%. Considering the whole study period, the RSV
      epidemics started in October-November and ended in May, showing a peak incidence
      in February, with a median of 28.1% and a maximum of 48.9%. Analysis of monthly
      distribution of each year of the study showed a biennial trend for an earlier
      appearance. A different epidemiological pattern of the infection was observed
      among the three national areas. In conclusion, even though the mechanism
      governing RSV infection periodicity remains unknown, its awareness in the absence
      of an RSV surveillance system as in Italy, may be useful for scheduling RSV
      prophylaxis and for hospital resource management.

PMID- 16608124
TI  - Erythema infectiosum following generalized petechial eruption induced by human
      parvovirus B19.
AB  - Parvovirus B19 is a DNA virus responsible for a wide spectrum of clinical
      illnesses. Among dermatological manifestations, the most common is erythema
      infectiosum, also known as the fifth disease. In 1990 Harms et al first described
      a papular-purpuric gloves and socks syndrome (PPGSS) due to parvovirus B19. It is
      an acute acral dermatosis characterized by an eruption of petechiae and small
      purpuric papules affecting the hands and feet in a gloves-and-socks distribution.
      Recently it was observed that PPGSS may be associated with involvement of the
      peri-oral region and the chin (acropetechial syndrome) and other sites provoking
      unusual presentation of the rash. We describe a patient with an acral purpura
      with the features of the "acropetechial syndrome" involving the buttocks, genital
      and axillary regions who subsequently developed a maculopapular eruption with the
      characteristics of the fifth disease. Parvovirus B19 DNA was detected by
      polymerase chain reaction (PCR) both in skin vasculitic lesions and in the serum
      during the petechial eruption, before the onset of antibodies. The immune
      response coincided with the development of the exanthem, suggesting a direct role
      of parvovirus B19 in the pathogenesis of endothelial cell injury.

PMID- 16608125
TI  - Antimicrobial resistance in Salmonella enteritidis from foods involved in human
      salmonellosis outbreaks in southern Brazil.
AB  - The antimicrobial resistance of Salmonella Enteritidis (n = 79) isolated from
      foods involved in human salmonellosis outbreaks in Southern Brazil during the
      period of 2001 to 2002 was analysed. The isolates were individually tested using
      the disc diffusion method against 10 antimicrobial agents. Most isolates were
      susceptible to all drugs tested. No S. Enteritidis isolates were resistant to
      sulfamethoxazole/trimethoprim or sulfazotrim and only one was resistant to
      chloramphenicol. The predominant resistance observed was to nalidixic acid
      (21.5%), gentamicin (12.7%), and streptomycin (11.4%), while intermediate
      resistance was observed most often for kanamycin (29.1%), neomycin (17.7%), and
      streptomycin (13.9%). Resistance was verified in 30 isolates (30.97%) grouped in
      14 different patterns. Resistance to more than one agent was verified in 13
      (16.46%) of the isolates. Two isolates were resistant to four drugs and only one
      strain presented resistance to three antibiotics.

PMID- 16608126
TI  - Invasion of murine respiratory tract epithelial cells by Chryseobacterium
      meningosepticum and identification of genes present specifically in an invasive
      strain.
AB  - Chryseobacterium meningosepticum causes severe infections in infants or adults
      with underlying illness. The species is highly heterogeneous, genetically
      composed of subgroups with different pathogenicity. Eight strains of C.
      meningosepticum, representing four different genomic subgroups, were evaluated
      for their ability to penetrate Madin-Darby Canine Kidney (MDCK) epithelial cell
      monolayers and serum resistance. None of the strains showed cytotoxicity or
      penetration to the MDCK cells. All displayed resistance to the bactericidal
      activity of various normal human sera. A murine pulmonary infection model was
      used to compare the pathogenicity between a clinical isolate and an environmental
      isolate. C. meningosepticum were cleared from the lung of infected mice within 7
      days following the intratracheal challenge. Electron microscopy demonstrated the
      large membrane protrusions, indicative of ruffles, and smaller, less organized
      membrane structures of the respiratory epithelial cells induced by the clinical
      isolate. Bacteria were observed to enter the cells as single entities in spacious
      vacuoles. Suppressive subtraction hybridization identified in the invasive
      isolate 35 distinct sequences associated with systems of energy production and
      conversion, transport, and secretion. In most cases, the identities between the
      references and the amino acid sequences deduced were low, suggesting that the
      functions of these sequences remain unknown.

PMID- 16608127
TI  - HBV genotypes and antiviral-resistant variants in HBV infected subjects in
      Northern Italy.
AB  - HBV genotypes were investigated in sera/plasma from 97 HBV positive subjects.
      Genotype D was revealed in 80.4% followed by E in 6.2%. Genotypes A, B, and C
      were also found, as well as for the first time a new combination of HBV D and G
      genotypes. In a cohort of subjects of this population, the relationship with
      lamivudine and/or famciclovir-resistant HBV mutants was also investigated. Among
      12 untreated subjects, 25% carried HBV drug-resistant strains suggesting that
      drug-resistant variants naturally exist in untreated Italian HBV chronically
      infected subjects.

PMID- 16608128
TI  - Detection of human papilloma virus in women attending the IRCCS, Ospedale
      oncologico Bari, Southern Italy: preliminary data.
AB  - We investigated the diffusion of HPV genotypes using molecular methods. HPV DNA
      was detected in 30.4% of women examined. The genotype HPV 16 was the most common
      followed by HPV 31, HPV 51 and HPV 58. Mixed infections were observed in 30.4% of
      HPV positive women. The 66.7% of the lower age group (< 35 years) was HPV
      positive. HPV infection was associated with the presence of morphological
      abnormalities in 13.7% of the women examined. The presence of HPV DNA in women
      younger than 35 years is an indication for the implementation of sexually
      transmitted disease education in our area to prevent potentially dangerous
      infections.

PMID- 16608129
TI  - Rapid detection and identification of Mycobacterium tuberculosis by Real Time PCR
      and Bactec 960 MIGT.
AB  - We have developed a Real-Time PCR assay to detect M. tuberculosis using the
      iCycler iQ detection system by TaqMan assay directly on the clinical specimen. A
      total of 513 clinical samples were taken from patients with suspected
      tuberculosis and other patients that had an active mycobacterial infection, as
      well as patients with diagnosed tuberculosis who were receiving antitubercular
      therapy. The sensitivity and specificity of this assay, 10% and 100%,
      respectively, were compared to those of conventional microbiological methods.

PMID- 16608130
TI  - Production of nitric oxide, lipid peroxidation and oxidase activity of
      ceruloplasmin in blood of elderly patients with primary hypertension. Effects of
      perindopril treatment.
AB  - BACKGROUND AND AIMS: One of the factors playing a role in both the aging process
      and the etiopathogenesis of primary hypertension is oxidative stress. The purpose
      of this work was to estimate the production of nitric oxide (NO), oxidase
      activity of ceruloplasmin (Cp) and level of malondialdehyde (MDA), the end
      product of lipid peroxidation in the blood of elderly patients with primary
      hypertension. The influence of treatment with the angiotensin-converting enzyme
      inhibitor perindopril (P) on the above parameters was also ascertained. METHODS:
      The study was carried out on 37 patients (69-91 yrs) with primary hypertension,
      treated with perindopril for 6 weeks, and normotensive subjects who constituted
      the two control groups: 25 (65-96 yrs--K1) and 23 (22-41 yrs--K2). Cp oxidase
      activity in serum, MDA level expressed as the concentration of substances
      reacting to thiobarbituric acid in red blood cells, and production of NO
      (concentration of nitrite/nitrate in plasma) by the Griess reaction were all
      determined. RESULTS: In the group of patients with hypertension, Cp activity was
      significantly higher than that in the control groups (K1 and K2). MDA
      concentrations in the erythrocytes of patients with hypertension were
      significantly higher than in the control groups and hypertensive patients had a
      lower NO (nitrite/nitrate) levels in plasma when compared with controls. In
      patients with hypertension, after only 7 days of therapy a substantial decrease
      in Cp oxidative activity was found, although the lowest value was observed after
      6 weeks of therapy. Nevertheless, significantly lower MDA was observed after 6
      weeks of therapy, corresponding to the values obtained in controls (K1 and K2).
      After 6 weeks of perindopril therapy, NO (nitrite/nitrate) was statistically
      higher in comparison with the values obtained before therapy. CONCLUSIONS:
      Results confirm intensification of oxidative stress and disorders in the
      production of NO in elderly patients with primary hypertension, and indicate the
      beneficial antioxidant effect of P.

PMID- 16608131
TI  - Neural mechanisms underlying balance improvement with short term Tai Chi
      training.
AB  - BACKGROUND AND AIMS: Though previous research has shown that Tai Chi reduces
      falls risk in older adults, no studies have examined underlying neural mechanisms
      responsible for balance improvement. We aimed to determine the efficacy of Tai
      Chi training in improving neuromuscular response characteristics underlying
      balance control in balance-impaired older adults. METHODS: Twenty-two balance
      impaired older adults were randomly divided into Tai Chi (TC) or control groups.
      Nineteen subjects (age 68-92, BERG 44 or less) completed the study. TC training
      included repetitive exercises using TC motor and biomechanical strategies,
      techniques, and postural elements. Control training included axial mobility
      exercises, balance/awareness education and stress reduction. Groups trained 1.5
      hours/day, 5 days/week for 3 weeks. After post-testing the control group received
      TC training. Subjects walked across a force plate triggered to move forward 15 cm
      at 40 cm/sec at heel strike. Tibialis anterior (TA) and medial gastrocnemius (GA)
      responses during balance recovery were measured with electromyograms (EMGs). Four
      clinical measures of balance were also recorded. RESULTS: TC subjects, but not
      controls, significantly reduced both TA response time from 148.92 +/- 45.11 ms to
      98.67 +/- 17.22 ms (p < or = 0.004) and occurrence of co-contraction of
      antagonist muscles (p < or = 0.003) of the perturbed leg. Clinical balance
      measures also significantly improved after TC. CONCLUSIONS: TC enhanced
      neuromuscular responses controlling the ankle joint of the perturbed leg. Fast,
      accurate neuromuscular activation is crucial for efficacious response to slips or
      trips.

PMID- 16608132
TI  - Seasonal changes in orthostatic hypotension among elderly admitted patients.
AB  - BACKGROUND AND AIMS: Orthostatic hypotension (OH) is a common finding among older
      patients. It has been shown that blood pressure (BP) is lower in summer than in
      winter. The aim of this study was to examine whether OH varies between seasons in
      the elderly population. METHODS: Five hundred and two inpatients (241 males, 261
      females) of mean age 81.6 years were included in the study; 253 were studied in
      summer and 166 in winter. Orthostatic tests were performed 3 times daily, 30
      minutes after meals. Orthostatic hypotension was defined as a decrease of at
      least 20 mmHg in systolic BP and/or 10 mmHg in diastolic BP upon assuming an
      upright posture at least twice during the day. RESULTS: OH was documented in 107
      patients (34.8%). Initial BP did not differ between seasons (147.6 +/- 24.6 /
      72.6 +/- 14.5 mmHg in summer, 146.7 +/- 23.4 / 71.5 +/- 13.4 mmHg in winter).
      However, the orthostatic drop in BP in the morning was greater in summer (-8.4 / 
      2.8 mmHg vs -4.3 / +0.2 mmHg in winter; p < 0.05). OH was also more prevalent in
      summer than in winter (37.9 vs 27.1%; p = 0.02). After adjustment for all
      confounders, the risk of experiencing OH in summer was 64% higher than in winter
      [adjusted odds ratio (OR) 1.64 [95% Confidence Interval (CI) 1.03-2.61].
      CONCLUSIONS: The prevalence of OH is higher in summer than winter. Thus, more
      attention should be paid to the diagnosis of OH in summer.

PMID- 16608133
TI  - Interviews or medical records, which type of data yields the best information on
      elderly people's health status?
AB  - BACKGROUND AND AIMS: Self-reported data and/or medical records are often used to
      assess the prevalence of illness and impairment in epidemiological studies.
      However, these two data sources do not always provide the same information. The
      aim was to compare data from interviews and medical records regarding illness,
      symptoms and impairment in the elderly, and to analyze the agreement between a
      consensus from both data sources and data from interviews and medical records,
      respectively. METHODS: We interviewed 130 persons (age range 67-99) regarding
      socio-demographic background data and physical and mental health. Medical records
      were reviewed. Illness burden was rated according to the Cumulative Illness
      Rating Scale for Geriatrics, and was rated in three ways based on: (1) interview
      data; (2) medical records; (3) information from both interviews and medical
      records considered to be consensus. Agreement was measured by the Kappa
      coefficient and the Svensson Paired Rank Measurement. A permutation test tested
      whether the ratings from interviews and medical records had the same agreement
      when compared with consensus. RESULTS: Statistically significant differences in
      agreement were found between interview versus consensus and medical records
      versus consensus for the vascular system (medical records best),
      eyes/ears/nose/throat/larynx and musculoskeletal/integument (interview best).
      Medical records gave better in formation concerning specific diseases and
      diagnoses, whereas interview data provided a better measure of illness,
      functional impairment and health in a broader sense. CONCLUSIONS: Both medical
      records and interviews yield good information of elderly people's health status,
      but they focus on different aspects of health.

PMID- 16608134
TI  - Actual practice vs guidelines in laboratory monitoring of older patients with
      primary hypothyroidism in primary care.
AB  - BACKGROUND AND AIMS: Clinical guidelines are produced in order to achieve an
      acceptable standard of care, especially for patients with common diseases in
      primary care. The treatment of primary hypothyroidism serves as an example of the
      content of clinical guidelines and actual practice. The aim of this study was to
      compare the follow-up of primary hypothyroidism by thyroid function tests, serum
      TSH and serum-free T4, in older patients managed in primary care, with
      recommendations in treatment guidelines and textbooks. METHODS: Participation
      rate 82% (n=1260), mean age 74 years, (range 64-100 yrs). Patients with primary
      hypothyroidism were identified by means of cross-sectional survey (Lieto Study
      1998-1999) and 4-year retrospective collection of laboratory database medical
      records (1994-1998), performed in autumn 2003. RESULTS: In most stable (=treated
      for more than 14 months) thyroxine users, both serum TSH (mean 1.4
      measurements/year) and serum-free T4 (mean 0.8 measurements/year) values were
      measured over the 4-year period of thyroxine treatment. 66.4% of serum TSH and
      85.3% of serum-free T4 values were within normal range. 41.7% of serum-free T4
      determinations had been performed without indication (=with TSH in normal range).
      CONCLUSIONS: Compared with the recommended testing frequency given in various
      guidelines, a considerable number of extra measurements, especially serum-free
      T4, were performed. However, some key issues in the recommendations were
      difficult to interpret, and the age or other main characteristics of the patient
      were not taken into consideration adequately.

PMID- 16608135
TI  - Physical and psychological functioning of daily living in relation to physical
      activity. A longitudinal study among former elite male athletes and controls.
AB  - BACKGROUND AND AIMS: Physical exercise plays an important role in the prevention
      and reduction of disabilities in elderly people. The aim of this study was to
      determine the role of physical activity in the physical and psychological
      functioning of daily living in a cohort of former elite male athletes
      representing different sports, and controls of middle and old age. METHODS:
      Subjects were 664 former elite male athletes (mean age 64.4 years) and 500
      controls (62.0 years) in middle and old age. Subjects were mailed "Physical
      activity and health survey" questionnaires in 1985 and 1995. The primary outcomes
      the physical and psychological functioning of daily living--were assessed in 1995
      using items from the Mini-Finland Health Survey. Logistic regression was used for
      longitudinal as well as cross-sectional analyses to estimate odds ratios (OR) for
      poor physical and psychological functioning of daily living in relation to
      recreational physical activity adjusted for age, sport group, life-style, BMI,
      mood, chronic diseases, personality characteristics, life-events and socio
      economic status. RESULTS: In the longitudinal analysis, low levels of physical
      activity (lowest MET quintile vs highest quintile) in 1985 (OR 4.91, 95%
      confidence interval (CI) 2.02-11.9), older age (> or =70 yrs vs under 60 yrs OR
      9.93, 95% CI 4.90-20.2), depression (OR 2.03, 95% CI 1.01-4.09) and anxiety in
      1995 (OR 2.67, 95% CI 1.34-5.32) increased the risk of poor physical functioning
      of daily living in 1995, whereas an increase in a physical activity between 1985
      1995 (OR 0.89, 95% CI 0.83-0.95) protected against poor physical functioning of
      daily living. A history of participating in specific types of sports, especially
      among certain power sports (weight-lifting and track & field throwers) (OR 0.19,
      95% CI 0.06-0.60) and team sports (OR 0.34, 95% CI 0.15-0.81) did reveal a
      significant protective effect against poor psychological functioning of daily
      living in the longitudinal analysis. CONCLUSIONS: This study suggests that an
      increase in physical exercise supports physical daily functionality. A specific
      history of sports participation promotes psychological well-being at an older
      age.

PMID- 16608136
TI  - Effects of a group-based exercise program on functional abilities in frail older
      women after hospital discharge.
AB  - BACKGROUND AND AIMS: An acute illness may place older frail people at increased
      risk of losing independence in functional abilities. Physical exercise may reduce
      the risk by improving muscle strength and balance. However, the effects of
      physical training on functional abilities have not been studied among frail, very
      old people recovering from an acute illness. The aim of this study was to
      determine the effects of a group-based exercise program on their ability to carry
      out self-care (ADL) and instrumental activities (IADL) relevant to daily life
      after discharge from hospital. METHODS: This randomized controlled trial examined
      68 community-dwelling women aged 75 years or older (mean age 83.0, SD 3.9) who
      were hospitalized due to an acute illness, and were mobility-impaired at
      admission. Participants were recruited from the geriatric ward of a primary-care
      health-center hospital, and were randomized into group-based strength training
      (n=34) and control (n=34) groups. The 10-week group-based intervention included
      strength training and functional exercises. The control group received
      instructions for a home exercise training program, including functional exercises
      but no further encouragement to exercise. The level of independence in ADL and
      IADL was evaluated, using a 13-item scale with stepwise grading from fully
      independent to fully dependent. Measurements took place immediately before and
      after the intervention, and three and nine months later. RESULTS: The
      intervention did not have any significant main effect (p = 0.407), nor was there
      any significant interaction between follow-up time and intervention (p = 0.854).
      CONCLUSIONS: The multicomponent outpatient strength training program did not
      improve autonomy in expert-evaluated ADL/IADL functions.

PMID- 16608137
TI  - Body mass index and functional recovery after hip fracture: a survey study of 510
      women.
AB  - BACKGROUND AND AIMS: Low body mass index (BMI) is associated with high risk of
      osteoporosis and fractures, but its impact on functional recovery after fractures
      is unknown. Our aim was to investigate the association between BMI and both
      functional recovery and period of rehabilitation in hip-fractured women. METHODS:
      510 out of 580 Caucasian women with hip fracture, admitted consecutively to a
      rehabilitation hospital, were investigated in this retrospective study.
      Functional recovery was assessed using the Barthel index score. RESULTS: In the
      510 women, BMI was 22.8 +/- 4.1 kg/m2 (mean +/- SD). After adjustment for age,
      femur bone mineral density, and the Barthel index assessed on admission to
      rehabilitation, a significant negative association was found between BMI and both
      the Barthel index score after rehabilitation and changes in it resulting from
      rehabilitation (p < 0.001). After adjustment for age and the Barthel index
      assessed on admission to rehabilitation, a significant positive association was
      found between BMI and period of rehabilitation (p < 0.001). The results were
      similar when BMI was evaluated either as individual values or after
      categorization according to World Health Organization criteria. CONCLUSIONS: In a
      sample of hip-fractured women, BMI was negatively associated with Barthel index
      scores and positively associated with period of rehabilitation. BMI may affect
      function after hip fracture, apart from hip fracture risk: subjects with higher
      BMI and low hip fracture risk may have poorer functional recovery in case of hip
      fracture, despite prolonged rehabilitation. Conversely, subjects with lower BMI
      and high hip fracture risk may have better functional recovery in case of hip
      fracture.

PMID- 16608138
TI  - Early re-hospitalization of elderly people discharged from a geriatric ward.
AB  - BACKGROUND AND AIMS: Hospitalized elderly patients generally have a high level of
      disability and comorbidity. In many cases, at hospital discharge, the achieved
      health status balance is poor, and consequently the risk of further disability
      and hospital readmission is great. Identifying factors leading to hospital
      readmission could be helpful in reducing such events. The aim of the study was to
      evaluate the incidence and predictive factors of hospital readmission. METHODS:
      We conducted an observational cohort study of a group of patients discharged from
      the Geriatric Ward of the San Giovanni Battista Hospital, Torino (Italy). The
      study sample contained 839 patients aged 80.6 +/- 6.3 years. The average hospital
      stay was 17.5 +/- 18.9 days (range 1-274 days). RESULTS: Follow-up lasted three
      months, at the end of which 107 patients (12.8%) had been readmitted, 83 (9.9%)
      had only one readmission and 24 (2.9%) one or more readmissions. The first
      readmission took place within 15 days of discharge for 24 patients (2.9%) and
      within 30 days of discharge for 27 (3.2%). A new hospital admission within 15
      days of discharge increased the risk of mortality (RR=3) and also the probability
      of a second re-hospitalization. 10.1% patients died; 88.2% of the patients who
      died had at least one readmission, whereas only 4.2% of live patients had a new
      hospital admission. CONCLUSIONS: Tumors, dementia, comorbidity, high education
      level, day hospital course and period of convalescence were all significantly and
      independently related to readmission.

PMID- 16608139
TI  - Early nutritional supplementation immediately after diagnosis of infectious
      disease improves body weight in psychogeriatric nursing home residents.
AB  - BACKGROUND AND AIMS: Many elderly people with Alzheimer's disease experience
      weight loss. Illness and inadequate regain after a period of illness are
      considered as contributory causes of progressive weight loss in psychogeriatric
      patients. We studied whether early use of a liquid nutrition supplement
      immediately after onset of acute illness from infection can prevent weight loss
      in elderly psychogeriatric nursing home residents. METHODS: Randomised controlled
      trial of 5 weeks after the onset of illness. Thirty-four psychogeriatric nursing
      home residents (aged > or =65 yrs) completed the study period. A liquid nutrition
      supplement (200 ml) once daily immediately after diagnosis of infection or
      standard treatment (enriched food after referral to a dietician) were provided.
      Body weight, mid-upper arm circumference, calf circumference, triceps skin fold
      thickness, dietary energy intake, and need for care were measured. RESULTS:
      Weight change during the study period was significantly different between the
      standard (-0.4 kg) and supplement (+0.8 kg) groups (p = 0.040). No significant
      differences were observed in changes of mid-upper arm circumference, triceps skin
      fold thickness, calf circumference or energy intake between groups. CONCLUSIONS:
      Early provision of a liquid nutrition supplement immediately after onset of acute
      illness from infection leads to weight gain in elderly psychogeriatric nursing
      home residents.

PMID- 16608140
TI  - Complications due to late diagnosis of celiac disease with co-existing plasma
      cell dyscrasia in an elderly patient.
AB  - Celiac disease is a genetic disorder, presenting with malabsorption-related
      problems because of mucosal damage after ingestion of gluten. The only known
      effective treatment is a gluten-free diet. Early diagnosis and treatment are
      essential in preventing complications due to malabsorption. Here we report the
      case of an elderly patient with a fifteen-year history of diarrhea, diagnosed
      with celiac disease, who had developed several complications due to malabsorption
      such as anemia, electrolyte imbalance and osteoporosis. We believe that late
      diagnosis of celiac disease had played a great role in the development of
      complications. Moreover, celiac disease poses an increased risk for all types of
      malignancies. Our patient also had concurrent plasma cell dyscrasia, but did not
      fulfil the criteria for diagnosis of multiple myeloma.

PMID- 16608141
TI  - An unusual cause of aspiration pneumonia.
AB  - We report a case of aspiration admitted to our rehabilitation unit in a patient
      with dysphagia due to diffuse idiopathic skeletal hyperostosis or Forestier's
      disease of the cervical spine, in whom an episode of pneumonia had occurred.
      Clinical and instrumental findings, including radiography of the spine, (CT Scan)
      and videofluoroscopy, confirmed the diagnosis. The dysphagia was hypothesized to
      be due to mechanical compression and inflammatory changes, accompanied by
      fibrosis in the esophagus wall. The aspiration pneumonia probably had
      multifactorial etiology: dysphagia, abnormal cough reflex, colonization of the
      oropharynx by virulent bacteria, etc. No aspiration pneumonia occurred after
      medical treatment and rehabilitation had been started. We review the medical
      literature on this unusual cause of aspiration pneumonia.

PMID- 16608142
TI  - Are U.S. women drinking less (or more)? Historical and aging trends, 1981-2001.
AB  - OBJECTIVE: Women's alcohol consumption in the United States has aroused increased
      public concern, despite a scarcity of evidence of any major increases in women's
      drinking. To help resolve this apparent inconsistency, we examined patterns of
      historical and age-related changes in U.S. women's drinking from 1981 to 2001.
      METHOD: In national surveys of women in 1981, 1991, and 2001, we measured the
      prevalence of 12-month and 30-day drinking, heavy episodic drinking (HED; six or
      more drinks per day), and subjective intoxication. Using these data, we analyzed
      time and age trends for six 10-year age groups in each survey, taking into
      account effects of repeated observations and possible covariates (ethnicity,
      marital status, and education). RESULTS: Women's 12-month drinking did not change
      significantly between 1981 and 1991, but it became more prevalent in the total
      samples between 1991 and 2001. Among 12-month drinkers, however, 30-day
      abstinence increased from 1981 to 2001 (particularly among women drinkers ages 21
      30). From 1981 to 2001, HED declined (particularly among women drinkers ages 21
      30), but intoxication became more prevalent (particularly among women drinkers
      ages 21-50). Drinking, HED, and intoxication became consistently less prevalent
      with increasing age. CONCLUSIONS: Among drinkers, increases in 30-day abstinence
      and declines in HED suggest that recent alarms about women's drinking may have
      been overstated. The contrast of lower rates of HED but increased reports of
      intoxication may indicate that women are more alert to alcohol's effects now than
      in earlier decades.

PMID- 16608143
TI  - ALDH2*2 is associated with a decreased likelihood of alcohol-induced blackouts in
      Asian American college students.
AB  - OBJECTIVE: A recent report found the heritability estimate for alcohol-induced
      blackouts was 53%. The present study was designed to determine whether possession
      of two specific genetic variations, an aldehyde dehydrogenase ALDH2*2 allele and
      an alcohol dehydrogenase ADHIB*2 allele, were associated with lower rates of
      lifetime blackouts. METHOD: Asian American college students (N=403) of Chinese
      and Korean descent were genotyped at the ALDH2 and ADHIB loci and assessed for
      lifetime alcohol-induced blackouts and the maximum number of drinks ever consumed
      in a 24-hour period. RESULTS: Participants who had an ALDH2*2 allele had
      approximately one third the risk of having a lifetime blackout of participants
      without this allele. Rates of experiencing a lifetime blackout did not
      significantly differ by ADHIB*2 status. Possessing an ALDH2*2 allele was
      associated with decreased risk of lifetime blackouts even after controlling for
      maximum number of drinks ever consumed in a 24-hour period and ethnicity.
      CONCLUSIONS: These findings suggest the protective effects of possessing an
      ALDH2*2 allele include a lowered risk of experiencing alcohol-induced blackouts.

PMID- 16608144
TI  - Predictors of untreated remission from late-life drinking problems.
AB  - OBJECTIVE: Studies of mixed-aged samples have suggested that a majority of
      problem drinkers achieve remission "naturally", without formal treatment. We
      sought to describe the life history predictors of untreated remission among older
      adults. METHOD: We compared 330 older untreated remitters to 120 older treated
      remitters and to 130 untreated nonremitters. RESULTS: A majority (73%) of
      remitted, older problem drinkers attained remission without any formal treatment
      for drinking problems. Compared with treated remitters, late-life untreated
      remitters were more likely to be women and had completed more schooling, reached
      their peak alcohol consumption and ceased development of new drinking problems
      earlier, had much less severe drinking and depression histories, and were less
      likely to have received any advice to reduce consumption. Compared with untreated
      nonremitters, untreated remitters were more likely to be women, reached their
      peak alcohol consumption and stopped developing new drinking problems almost a
      decade earlier, had somewhat less severe drinking histories, were less likely to
      have been advised to reduce consumption, and were more likely to have reacted to
      late-life health problems by reducing their alcohol consumption. CONCLUSIONS:
      Many late-life problem drinkers with milder drinking problems achieve remission
      without treatment or advice to reduce consumption. However, a notable percentage
      of untreated older individuals who have more severe drinking problems could
      benefit from public health efforts to aid detection of late-life drinking
      problems and interventions aimed at reducing alcohol consumption. Results suggest
      that such interventions should highlight the negative health consequences of
      excessive late-life drinking.

PMID- 16608145
TI  - Formal treatment, self-help, or no treatment for alcohol-use disorders? Evidence
      from the National Household Survey on Drug Abuse.
AB  - OBJECTIVE: The purpose of this study was to examine further alcohol treatment
      choice by using data from a nationally representative sample of adults with
      alcohol-use disorders to test which of three models-sequential, multinomial, or
      nested best fit the data. The goals were to provide evidence about how this
      choice was made and to provide improved coefficient estimates, as well as to
      inform future analyses of treatment choice. METHOD: Data from the 2000 National
      Household Survey of Drug Abuse include respondents ages 18-64 reporting symptoms
      consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition (DSM-IV) diagnoses of alcohol abuse or dependence. A nested multinomial
      framework is used to determine the preferred model and to estimate the effect of
      respondents' characteristics on the decisions to receive help and what kind of
      help to receive. RESULTS: A sequential model, in which the choice of whether to
      receive help is unaffected by the level of satisfaction afforded by the
      alternatives, best fit the data. Older respondents had higher odds of both
      receiving help and choosing self-help, and those with a DSM-IV diagnosis of abuse
      had lower odds of receiving help but higher odds of entering self-help.
      CONCLUSIONS: The decision to receive help for alcohol problems appears unaffected
      by the perceived differences between these two broad categories of alternatives:
      self-help or formal treatment. This result may indicate the need to provide more
      information on the full range of treatment options to those for whom self-help
      may not be sufficient.

PMID- 16608146
TI  - Music, substance use, and aggression.
AB  - OBJECTIVE: This study investigated whether young people's substance use and
      aggressive behaviors are related to their listening to music containing messages
      of substance use and violence. METHOD: Using self-administered questionnaires,
      data were collected from a sample of community-college students, ages 15-25 years
      (N=1056; 57% female). A structural equation model (maximum likelihood method) was
      used to simultaneously assess the associations between listening to various
      genres of music and students' alcohol use, illicit-drug use, and aggressive
      behaviors. Respondents' age, gender, race/ethnicity, and level of sensation
      seeking were included in the analyses as control variables. RESULTS: Listening to
      rap music was significantly and positively associated with alcohol use,
      problematic alcohol use, illicit-drug use, and aggressive behaviors when all
      other variables were controlled. In addition, alcohol and illicit-drug use were
      positively associated with listening to musical genres of techno and reggae.
      Control variables (e.g., sensation seeking, age, gender and race/ethnicity) were
      significantly related to substance use and aggressive behaviors. CONCLUSIONS: The
      findings suggest that young people's substance use and aggressive behaviors may
      be related to their frequent exposure to music containing references to substance
      use and violence. Music listening preference, conversely, may reflect some
      personal predispositions or lifestyle preferences. There is also the possibility
      that substance use, aggression, and music preference are independent constructs
      that share common "third factors".

PMID- 16608147
TI  - To what extent is intoxication associated with aggression in bars? A multilevel
      analysis.
AB  - OBJECTIVE: The purpose of this study was to assess the relationship between level
      of intoxication and the frequency and severity of aggression at the person,
      incident, visit, and bar level for aggressive incidents observed in bars or
      clubs. METHOD: Hierarchical Linear Modeling (HLM) analysis of 1025 incidents of
      aggression documented by trained observers during 1334 nights of observation in
      118 bars and clubs in Toronto, Canada, was conducted. RESULTS: Both level of
      intoxication of the crowd during the visit as well as mean level of intoxication
      at the bar level significantly predicted frequency of aggression. There was a
      positive association between level of intoxication and severity of aggression at
      both the incident and person level except for the highest level of intoxication
      at the person level, where severity of aggression was less than for moderate
      intoxication. A person-incident level interaction between intoxication and
      severity of aggression was also found. CONCLUSIONS: These results suggest that
      prevention efforts should focus on both identifying bars that typically have more
      intoxicated patrons and reducing the intoxication levels of patrons across bars
      generally. The results also showed a strong positive relationship between level
      of intoxication and severity of aggression (except at the highest levels),
      indicating that intoxication increases risk in terms of both frequency and
      severity of aggression. The significant interaction between person- and visit
      level intoxication suggests that greater attention needs to be paid to group
      dynamics in alcohol-related aggression.

PMID- 16608148
TI  - Sibling influence on alcohol use in a young adult, high-risk sample.
AB  - OBJECTIVE: Previous research has found that siblings resemble each other in terms
      of alcohol use but has not examined sibling influence in young adult or high-risk
      siblings. The current study tested whether siblings prospectively influenced each
      other's alcohol use and how gender matching, age differences, and family conflict
      might moderate such effects. METHOD: Data from sibling pairs (n=169 pairs) in an
      ongoing longitudinal study of children of alcoholics and matched controls were
      collected at two time points 5 years apart. RESULTS: Older sibling alcohol use
      predicted younger sibling alcohol use, even after controlling for membership in a
      shared peer group and for parental alcoholism. However, moderator variables
      qualified this effect, such that older sibling influence was significant only
      among sibling pairs who were of the same gender, closer in age, and from higher
      conflict families. Younger sibling influence was significant only for sibling
      pairs close in age, suggesting the presence of reciprocal peer-like effects in
      this subgroup. CONCLUSIONS: The current study provides evidence for sibling
      influence on alcohol use into adulthood, but the extent of this influence depends
      on sibling similarity in age and gender and on levels of family conflict.
      Implications for family-based theory and intervention efforts are discussed.

PMID- 16608149
TI  - Predicting negative drinking consequences: examining descriptive norm perception.
AB  - OBJECTIVE: This study explored how much variance in college student negative
      drinking consequences is explained by descriptive norm perception, beyond that
      accounted for by student gender and self-reported alcohol use. METHOD: A
      derivation sample (N=7565; 54% women) and a replication sample (N=8924; 55.5%
      women) of undergraduate students completed the Campus Alcohol Survey in classroom
      settings. RESULTS: Hierarchical regression analyses revealed that student gender
      and average number of drinks when "partying" were significantly related to
      harmful consequences resulting from drinking. Men reported more consequences than
      did women, and drinking amounts were positively correlated with consequences.
      However, descriptive norm perception did not explain any additional variance
      beyond that attributed to gender and alcohol use. Furthermore, there was no
      significant three-way interaction among student gender, alcohol use, and
      descriptive norm perception. CONCLUSIONS: Norm perception contributed no
      significant variance in explaining harmful consequences beyond that explained by
      college student gender and alcohol use.

PMID- 16608150
TI  - Effects of heavy drinking by maritime academy cadets on hangover, perceived
      sleep, and next-day ship power plant operation.
AB  - OBJECTIVE: The effects of an evening of heavy drinking on next-day occupational
      performance are mixed across studies and have not been investigated for ship
      handling performance. Furthermore, it is not known whether the residual effects
      of alcohol on next-day performance are due to its effects on sleep. METHOD:
      Merchant marine cadets (N=61) who had been trained on a diesel power plant
      simulator and who drank heavily at least episodically were given placebo beer one
      evening and were randomized on a second evening to placebo or real beer that
      resulted in a mean breath alcohol concentration (BrAC) of .115 g%. After an 8
      hour sleep period, a meal, and a return to < or = .02 g% BrAC, cadets were
      assessed with self-report measures and the power plant simulator. RESULTS: No
      effects of beverage condition were seen on actual performance, although cadets
      who consumed alcohol rated their performance as impaired compared with the
      placebo conditions. Alcohol consumption also increased the Acute Hangover Scale
      score, improved perceived sleep quality, and decreased perceived latency to sleep
      onset while not affecting perceived sleep duration. CONCLUSIONS: While residual
      alcohol effects are found on some complex performance tasks, residual effects of
      .11 to .12 g% BrAC were not seen on ship engine simulator performance despite
      increased hangover symptoms and perceived impairment from the hangover.
      Therefore, this level of heavy drinking might not be deleterious to next-day
      routine occupational performance by young ship engineers despite the subjective
      ill effects. The perception that alcohol improves sleep onset might be a
      motivation for some to drink heavily. The effects on older engineers, at higher
      alcohol levels, and on other ship-handling tasks still need to be studied.

PMID- 16608151
TI  - Physical and psychomotor functioning of females the morning after consuming low
      to moderate quantities of beer.
AB  - OBJECTIVE: Individuals in society typically consume alcohol in "standard" units
      (e.g., bottles/cans of beer, glasses of wine, shots of distilled spirits) over a
      reasonable period of time whereas in many hangover studies, participants consume
      a single large dose of alcohol relative to their body weight in a short period of
      time. The purpose of this study was to examine how consuming low to moderate
      "standard" quantities of alcohol over an evening affected subjective hangover
      ratings, physical, physiological, and psychomotor functioning of adult females
      the next morning. METHOD: Twelve females consumed zero, two, four, or six bottles
      of beer (341 ml; 5% weight by volume) in a within-subjects design. Blood alcohol
      concentration, resting heart rate, resting blood pressure, and grip strength were
      measured prior to consumption, 1 hour after consumption, and the following
      morning (9 hours after consumption). In the morning, participants rated the
      presence of eight hangover symptoms, completed a four-choice reaction time test,
      and performed tests of submaximal and maximal endurance on a treadmill; blood
      lactate, blood glucose, and perceived exertion were recorded during submaximal
      and maximal exercise. RESULTS: Heart rate, blood pressure, grip strength, blood
      lactate, blood glucose, and reaction time did not significantly change the next
      morning as a function of alcohol dose. Participants made more choice reaction
      errors after consuming six than zero bottles of beer. CONCLUSION: These results
      suggest that consuming moderate quantities of beer affects decision making but
      not physical and physiological performance in adult females the next morning.

PMID- 16608152
TI  - Higher prevalence of systemic hypertension among moderate alcohol drinkers: an
      exploration of the role of underreporting.
AB  - OBJECTIVE: Heavy alcohol drinking is associated with increased prevalence of
      systemic hypertension (HTN), but the relationship between moderate drinking and
      HTN remains unclear. We explored the possible role of underreporting among
      moderate drinkers. METHOD: In a cross-sectional analysis of 105,378 persons, we
      defined a subset among persons reporting three or fewer drinks per day that was
      likely to include a disproportionate number of underreporters. This subset
      included persons who, on another occasion, indicated intake of three or more
      drinks per day or who ever had a diagnosis of an alcohol-related condition; these
      persons are called "positive." Persons who never reported three or more drinks
      per day and who had no alcohol-related diagnosis were called "negative." Logistic
      regression models estimated the odds ratios (ORs) for prevalent HTN (140/90 mm Hg
      or greater) in the positive and negative subgroups, compared with lifelong
      abstainers as referent. All persons and four race-gender groups were studied, and
      they were controlled for age, education, smoking, and body mass index. We also
      studied the relationship of blood liver transaminase enzyme levels in the
      positive and negative subgroups at specific alcohol intake strata. RESULTS: For
      persons reporting one to two drinks per day, the OR (95% confidence interval) of
      HTN was 1.32 (1.21-1.43) for positive persons and 1.16 (1.09-1.25) for negative
      persons. For those reporting less than one drink per day, the ORs were 0.97 (0.89
      1.06) for positives and 0.92 (0.87-0.98) for negatives. For those reporting one
      to two drinks per day, positive/negative comparisons showed approximately a 75%
      increased prevalence of high liver transaminase enzymes. For those reporting less
      than one drink per day, the positive/negative difference was approximately 30%.
      CONCLUSION: In these data, increased prevalence of HTN among persons reporting
      one to two drinks per day appears to be partially due to underreporting of
      alcohol intake.

PMID- 16608153
TI  - Alcohol consumption and health-services utilization in Germany.
AB  - OBJECTIVE: This study tests two hypotheses. The first is that a U-shaped or
      inverse linear association exists between alcohol consumption and health-services
      utilization. Although this relationship has been examined previously, conclusions
      have been inconsistent. Additional research is needed to explain why abstainers
      use more health services than drinkers. Our second hypothesis is that abstainers
      with a history of heavy drinking seek out more health services than those without
      heavy drinking histories. METHOD: Data were from two surveys conducted in Germany
      (N's=4268 [51% women] and 6857 [52% women]). Alcohol consumption was assessed
      using a quantity-frequency measure. RESULTS: Outpatient and inpatient services
      showed an inverse linear relation with alcohol consumption. Among abstainers,
      those with a drinking history exhibited a higher use of outpatient visits but
      were not more likely to have been hospitalized. CONCLUSIONS: This study supports
      the view that alcohol consumption is associated with decreased utilization of
      health services. Results provide some evidence for the hypothesis that former
      heavy drinkers have higher health-services utilization than either moderate
      drinkers or other abstainers.

PMID- 16608154
TI  - Preference-weighted health status associated with substance use-disorders
      treatment.
AB  - OBJECTIVE: Cost-effectiveness analyses using preference-weighted health status as
      the measure of effectiveness allow for the direct comparison of cost
      effectiveness ratios for physical and mental health interventions. However, these
      analyses are not commonly used for substance use-disorders interventions. We
      conducted a methodological evaluation of the relationship between preference
      weighted health status and 6-month substance use-disorders treatment outcomes.
      METHOD: The design was an observational study of clients receiving substance use
      disorders treatment. Fifteen high-volume treatment centers within a regional
      managed behavioral health care organization participated. There were 165 subjects
      (117 men, 48 women) diagnosed with current Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, substance dependence in the analysis. Baseline
      and 6-month data included substance-use quantity, frequency, and diagnostic
      criteria and preference-weighted Medical Outcomes Study Short Form-36 scores
      based on visual analog scale (VAS) and standard gamble (SG) conversion formulas.
      RESULTS: Controlling for sociodemographic variables, VAS change for early
      remission at 6 months was 0.107 (p = .0002) (reference category continued
      dependence). SG change for early remission at 6 months was 0.041 (p < .0004).
      Using heavy drinkers as the reference category, VAS preference-weighted change
      was 0.062 (p = .10) for abstinent and 0.112 (p = .01) for moderate drinkers. SG
      preference-weighted change was 0.027 (p = .08) for abstinent and 0.046 (p = .01)
      for moderate drinkers. CONCLUSIONS: These findings support the construct validity
      of preference-weighted health status in substance use-disorders treatment. Direct
      comparisons of the cost-effectiveness of substance use-disorders treatment with
      other mental or physical health interventions are critical during times of
      limited health care resources.

PMID- 16608155
TI  - Alcohol consumption, alcoholics anonymous membership, and suicide mortality
      rates, Ontario, 1968-1991.
AB  - OBJECTIVE: The goal of this study is to identify alcohol-related factors that
      influence mortality rates from suicide. Specifically, we examine the impact of
      per capita consumption of total alcohol, distilled spirits, and beer and wine;
      unemployment rate; and Alcoholics Anonymous (AA) membership rate on total and
      male and female suicide mortality rates in Ontario between 1968 and 1991. METHOD:
      We studied the impact of alcohol consumption levels, AA membership rates, and
      unemployment rates on suicide mortality rates in Ontario from 1968 to 1991. Time
      series analyses with Auto Regressive Integrated Moving Average (ARIMA) modeling
      were applied to total and male and female suicide rates. The analyses performed
      included total alcohol consumption, distilled spirits consumption, beer
      consumption, and wine consumption. Missing AA membership data were interpolated
      with cubic splines. RESULTS: Total alcohol consumption and consumption of each of
      beer, distilled spirits, and wine were significantly and positively related to
      total and female suicide mortality rates. AA membership rates were negatively
      related to total and female suicide rates. Although data for males did not reach
      significance (except for the relationship between wine consumption and suicide
      rate), the direction of effects was consistent with that observed for female and
      total suicide rates. Unemployment rates were positively related to male and total
      suicide rates in some models. CONCLUSIONS: These data confirm the important
      relationships between per capita consumption measures and suicide mortality rates
      seen by previous investigators. Additionally, the results for AA membership rates
      are consistent with the hypothesis that AA membership and treatment for misuse of
      alcohol can exert beneficial effects observable at the population level.

PMID- 16608156
TI  - Automated telephone screening for problem drinking.
AB  - OBJECTIVE: This study assessed test-retest reliability and criterion validity for
      an automated version of the Alcohol Use Disorders Identification Test (AUDIT), a
      screening tool for alcohol-related problems. Participants' willingness to use
      such a system to learn about and change their drinking behavior was also
      assessed. METHOD: Participants were 202 callers recruited through newspaper ads
      and flyers asking for volunteers concerned about their drinking and willing to
      help test a new method of screening and referral for alcohol problems.
      Participants were divided into two groups. The first group of subjects recruited
      received the Telephone-Linked Communications (TLC)-AUDIT twice, administered a
      week apart. The second group received the TLC-AUDIT once and a human-administered
      AUDIT once, also a week apart. RESULTS: Test-retest reliability was assessed in
      102 participants; the intraclass correlation of AUDIT scores between both
      administrations was .87; kappa for nonproblem versus problem drinking (AUDIT
      score of 8 or above) was .89. The validity study compared the TLC-AUDIT scores of
      the next 100 participants to AUDIT questions administered by a human interviewer.
      The intraclass correlation was .94; kappa was .75. Seventy-five percent of all
      participants who screened positive for problem drinking agreed they would "talk
      to a computer again to learn more about your drinking pattern and how to deal
      with it". CONCLUSIONS: Automated telephone technology can be used to administer
      the AUDIT instrument with high levels of reliability and validity. This
      technology could be used to deliver behavioral change interventions.

PMID- 16608157
TI  - Acculturation and driving under the influence: a study of repeat offenders.
AB  - OBJECTIVE: In California, driving under the influence (DUI) arrest and conviction
      rates are disproportionately higher among the Hispanic population. Acculturation
      and other factors associated with drinking and driving may help explain this
      disparity. METHOD: Interviews with Hispanic repeat DUI offenders were conducted
      immediately prior to sentencing and 2 years later. Arrest records from these
      offenders were also examined. Analyses were performed to examine the association
      between acculturation and other sociodemographic characteristics at baseline with
      DUI arrests and convictions at a 2-year follow-up. RESULTS: Logistic regression
      modeling showed that acculturation was significantly related to self-reported DUI
      recidivism even after controlling for other factors associated with DUI
      convictions during a 2-year follow-up. Acculturation was not found to have a
      statistically significant relation to DUI arrest rates during that same period.
      CONCLUSIONS: Among a Hispanic sample of repeat DUI offenders, the less
      acculturated members were more likely to report a repeat DUI conviction at 2-year
      follow-up than the more-acculturated ones, even after controlling for other
      characteristics associated with DUI behaviors, such as drinking severity and
      marital status. The same pattern was not found between acculturation and arrest
      rates. Acculturation may serve as a risk factor for repeat convictions. Efforts
      to reduce multiple DUI convictions may need to consist of ways to target persons
      who are less acculturated.

PMID- 16608158
TI  - Self-efficacy, therapeutic alliance, and alcohol-use disorder treatment outcomes.
AB  - OBJECTIVE: High abstinence self-efficacy reliably predicts better treatment
      outcomes for patients with alcohol use disorders, but little is known about
      aspects of treatment that may be particularly beneficial for patients who enter
      treatment with low self-efficacy. This study examines whether the relationship
      between self-efficacy and treatment outcomes is influenced by the quality of the
      therapeutic alliance in Project MATCH (Matching Alcoholism Treatments to Client
      Heterogeneity), a multisite clinical trial of three treatments for alcohol use
      disorders. METHOD: Information on 785 patients in the outpatient sample of
      Project MATCH was used to test for an interaction between baseline self-efficacy
      and therapeutic alliance in relation to 1-year alcohol use outcomes. RESULTS: A
      significant interaction was found between self-efficacy and the therapists'
      perception of the therapeutic alliance predicting I1year drinking outcomes.
      Patients with low self-efficacy who established a strong treatment alliance, as
      judged by the therapist, experienced I1year outcomes that were superior to those
      of patients with low self-efficacy with poorer treatment alliance and comparable
      with those of patients with high self-efficacy. Therapeutic alliance was not
      strongly related to the outcomes of patients with high baseline self-efficacy.
      CONCLUSIONS: In patients who are treated for alcohol-use disorders, a positive
      therapeutic alliance may counteract the negative impact of a low baseline self
      efficacy. Potential reasons why the therapist's perception of the alliance may be
      particularly important for patients with low self-efficacy are discussed.

PMID- 16608159
TI  - The reliability and validity of the Alcohol Use Disorders Identification Test
      (AUDIT) in a German general practice population sample.
AB  - OBJECTIVE: Our goal was to analyze the retest reliability and validity of the
      Alcohol Use Disorders Identification Test (AUDIT) in a primary-care setting and
      recommend a cut-off value for the different alcohol-related diagnoses. METHOD:
      Participants recruited from general practices (GPs) in two northern German cities
      received the AUDIT, which was embedded in a health-risk questionnaire. In total,
      10,803 screenings were conducted. The retest reliability was tested on a
      subsample of 99 patients, with an intertest interval of 30 days. Sensitivity and
      specificity at a number of different cut-off values were estimated for the sample
      of alcohol consumers (n=8237). For this study, 1109 screen-positive patients
      received a diagnostic interview. Individuals who scored less than five points in
      the AUDIT and also tested negative in a second alcohol-related screen were
      defined as "negative" (n=6003). This definition was supported by diagnostic
      interviews of 99 screen-negative patients from which no false negatives could be
      detected. As the gold standard for detection of an alcohol-use disorder (AUD), we
      used the Munich-Composite International Diagnostic Interview (MCIDI), which is
      based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,
      criteria. RESULTS: On the item level, the reliability, measured by the intraclass
      correlation coefficient (ICC), ranged between .39 (Item 9) and .98 (Item 10). For
      the total score, the ICC was .95. For cut-off values of eight points and five
      points, 87.5% and 88.9%, respectively, of the AUDIT-positives, and 98.9% and
      95.1%, respectively, of the AUDIT-negatives were identically identified at
      retest, with kappa = .86 and kappa = .81. At the cut-off value of five points, we
      determined good combinations of sensitivity and specificity for the following
      diagnoses: alcohol dependence (sensitivity and specificity of .97 and .88,
      respectively), AUD (.97 and .92), and AUD and/or at-risk consumption (.97 and
      .91). CONCLUSIONS: Embedded in a health-risk questionnaire in primary-care
      settings, the AUDIT is a reliable and valid screening instrument to identify at
      risk drinkers and patients with an AUD. Our findings strongly suggest a lowering
      of the recommended cut-off value of eight points.

PMID- 16608160
TI  - Mechanisms of formation, genotoxicity, and mutation of guanine oxidation
      products.

PMID- 16608161
TI  - A 2-iminohydantoin from the oxidation of guanine.
AB  - The nucleobase guanine was oxidized with dimethyldioxirane (DMDO) to explore the
      role of epoxidizing agents in oxidative DNA damage. Treatment of guanine with 10%
      molar excess DMDO in aqueous solution at 0 degrees C and pH 7.5 followed by
      workup under mild conditions gave 5-carboxamido-5-formamido-2-iminohydantoin (1)
      as the sole isolable product in 71% yield. The structure of 1 was established on
      the basis of mass spectrometry and NMR studies on 1 and its isotopomers generated
      by the oxidation of [4-(13)C] and [7-(15)N]guanine, which yield [5-(13)C]1 and [7
      (15)N]1. The distribution of 13C and 15N labels in the isotopomeric products
      supports initial epoxidation of the C4-C5 bond of guanine followed by a 1,2-acyl
      migration of guanine C6. Compound 1 is suggested as a possible primary DNA lesion
      from putative epoxidizing agents, including hydroperoxides present during
      biological processes such as lipid peroxidation.

PMID- 16608162
TI  - Quantitative puff-by-puff-resolved characterization of selected toxic compounds
      in cigarette mainstream smoke.
AB  - Soft single photon ionization (SPI)-time-of-flight mass spectrometry (TOFMS) has
      been applied for the quantitative puff-by-puff-resolved characterization of
      selected toxic species in cigarette mainstream smoke, namely, nitric oxide (NO),
      acetaldehyde, butadiene, acetone, isoprene, benzene, toluene, ethyl benzene, and
      xylene. The 2R4F research cigarette was investigated for whole smoke (unfiltered)
      and gas phase (filtered). It has been demonstrated that the existing smoking
      regime for total smoke analysis (smoke from a complete cigarette) features
      deficiencies when applied to puff-resolved measurements. This is especially the
      case for analysis in which a glass fiber filter is used to separate the smoke
      particulate and gas phases because material is desorbed from the filter and
      influences succeeding puffs. Regarding whole smoke measurements, succeeding puffs
      are affected by contamination and memory effects of the smoking machine itself,
      but to a lower extent. Quantitative puff-resolved smoke profiles show that the
      puff yields of the various constituents can differ tremendously. Most species'
      concentrations increase gradually with puff number, which is mainly due to the
      reduction in length of the cigarette. However, high yields in the first puff are
      observed for butadiene and isoprene, suggesting different formation mechanisms
      for these compounds. First results are presented in which these high yields in
      the first puff are mainly associated with the gaseous fraction of the smoke.

PMID- 16608163
TI  - Exposure to wear particles generated from studded tires and pavement induces
      inflammatory cytokine release from human macrophages.
AB  - Health risks associated with exposure to airborne particulate matter (PM) have
      been shown epidemiologically as well as experimentally, pointing to both
      respiratory and cardiovascular effects. Lately, wear particles generated from
      traffic have been recognized to be a major contributing source to the overall
      particle load, especially in the Nordic countries were studded tires are used. In
      this work, we investigated the inflammatory effect of PM10 generated from the
      wear of studded tires on two different types of pavement. As comparison, we also
      investigated PM10 from a traffic-intensive street, a subway station, and diesel
      exhaust particles (DEP). Human monocyte-derived macrophages, nasal epithelial
      cells (RPMI 2650), and bronchial epithelial cells (BEAS-2B) were exposed to the
      different types of particles, and the secretion of IL-6, IL-8, IL-10, and TNF
      alpha into the culture medium was measured. The results show a significant
      release of cytokines from macrophages after exposure for all types of particles.
      When particles generated from asphalt/granite pavement were compared to
      asphalt/quartzite pavement, the granite pavement had a significantly higher
      capacity to induce the release of cytokines. The granite pavement particles
      induced cytokine release at the same magnitude as the street particles did, which
      was higher than what particles from both a subway station and DEP did. Exposure
      of epithelial cells to PM10 resulted in a significant increase of TNF-alpha
      secreted from BEAS-2B cells for all types of particles used (DEP was not tested),
      and the highest levels were induced by subway particles. None of the particle
      types were able to evoke detectable cytokine release from RPMI 2650 cells. The
      results indicate that PM10 generated by the wear of studded tires on the street
      surface is a large contributor to the cytokine-releasing ability of particles in
      traffic-intensive areas and that the type of pavement used is important for the
      level of this contribution. Furthermore, the airway inflammatory potential of
      wear particles from tires and pavement might be of a greater magnitude than that
      of DEP.

PMID- 16608164
TI  - Kinetics of O(6)-methyl-2'-deoxyguanosine repair by O(6)-alkylguanine DNA
      alkyltransferase within K-ras gene-derived DNA sequences.
AB  - O(6)-Methyl-2'-deoxyguanosine (O(6)-Me-dG) is a potent mutagenic DNA adduct that
      can be induced by a variety of methylating agents, including tobacco-specific
      nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). O(6)-Me-dG is
      directly repaired by the specialized DNA repair protein, O(6)-alkylguanine DNA
      alkyltransferase (AGT), which transfers the O(6)-alkyl group from the modified
      guanine to a cysteine thiol within the active site of the protein. Previous
      investigations suggested that AGT repair of O(6)-alkylguanines may be sequence
      dependent as a result of flanking nucleobase effects on DNA conformation and
      energetics. In the present work, a novel high-performance/pressure liquid
      chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI+-MS/MS)
      based approach was developed to analyze the kinetics of AGT-mediated repair of
      O(6)-Me-dG adducts placed at different sites within the double-stranded DNA
      sequence representing codons 8-17 of the K-ras protooncogene, 5'-G1TA G2TT G3G4A
      G5CT G6G7T G8G9C G10TA G11G12C AAG13 AG14T-3', where G5, G6, G7, G8, G9, G10, or
      G11 was replaced with O(6)-Me-dG. The second guanine of K-ras codon 12 (G7 in our
      numbering system) is a major mutational hotspot for G --> A transitions observed
      in lung tumors of smokers and in neoplasms induced in laboratory animals by
      exposure to methylating agents. O(6)-Me-dG-containing duplexes were incubated
      with human recombinant AGT protein, and the reactions were quenched at specific
      times. Following acid hydrolysis to release purines, isotope dilution HPLC-ESI
      MS/MS was used to determine the amounts of O(6)-Me-G remaining in DNA. The
      relative extent of demethylation for O(6)-Me-dG adducts located at G5, G6, G7,
      G8, G9, G10, or G11 following a 10 s incubation with AGT showed little variation
      as a function of sequence position. Furthermore, the second-order rate constants
      for the repair of O(6)-Me-dG adducts located at the first and second positions of
      the K-ras codon 12 (5'-G6G7T-3') were similar (1.4 x 10(7) M(-1) s(-1) vs 7.4 x
      10(6) M(-1) s(-1), respectively), suggesting that O(6)-Me-dG repair by AGT is not
      the determining factor for K-ras codon 12 mutagenesis following exposure to
      methylating agents. The new HPLC-ESI-MS/MS assay developed in this work is a
      valuable tool which will be used to further explore the role of local sequence
      environment and endogenous DNA modifications in shaping mutational spectra of NNK
      and other methylating agents.

PMID- 16608165
TI  - Oxidative deboronation of the peptide boronic acid proteasome inhibitor
      bortezomib: contributions from reactive oxygen species in this novel cytochrome
      P450 reaction.
AB  - Bortezomib (1) is a potent first-in-class dipeptidyl boronic acid proteasome
      inhibitor employed in the treatment of patients with relapsed multiple myeloma
      where the disease is refractory to conventional lines of therapy. The potency of
      1 is owed primarily to the presence of the boronic acid moiety, one which is
      suited to establish a tetrahedral intermediate with the active site N-terminal
      threonine residue of the proteasome. Hence, deboronation of 1 represents a
      deactivation pathway for this chemotherapeutic agent. Deboronation of 1 affords a
      near equal mixture of diastereomeric carbinolamide metabolites (M1/M2) and
      represents the principal metabolic pathway observed in humans. In vitro results
      from human liver microsomes and human cDNA-expressed cytochrome P450 enzymes
      (P450) indicate a role for P450 in the deboronation of 1. Use of 18O-labeled
      oxygen under controlled atmospheres confirmed an oxidative mechanism in the P450
      mediated deboronation of 1, as 18O was found incorporated in both M1 and M2.
      Chemically generated reactive oxygen species (ROS), such as those generated as
      byproducts during P450 catalysis, were also found to deboronate 1 resulting in
      the formation of M1 and M2. Known to undergo efficient redox cycling, P450 2E1
      was found to catalyze the deboronation of 1 predominantly to the carbinolamide
      metabolites M1 and M2, as well as to a pair of peroxycarbinolamides, 2 and 3. The
      presence of superoxide dismutase (SOD) and catalase prevented the deboronation of
      1, thus, supporting the involvement of ROS in the P450 2E1-catalyzed deboronation
      reaction. The presence of SOD and catalase also protected 1 against P450 3A4
      catalyzed deboronation, albeit to a lesser extent. The remaining deboronation
      activity observed in the P450 3A4 reaction may suggest the involvement of the
      more conventional activated enzyme-oxidants previously described for P450. Our
      present findings indicate that the oxidase activity of P450 (i.e., formation of
      ROS) represents a mechanism of deboronation.

PMID- 16608167
TI  - Impact of cytosine 5-halogens on the interaction of DNA with restriction
      endonucleases and methyltransferase.
AB  - Growing evidence from both prokaryotes and eukaryotes indicates that pyrimidine 5
      methyl groups can have profound biological consequences that are mediated by the
      affinity of DNA-protein interactions. The presence of the 5-methyl group could
      potentially create a steric block preventing the binding of some proteins whereas
      the affinity of many other proteins is substantially increased by pyrimidine
      methylation. In this paper, we have constructed a series of oligonucleotides
      containing cytosine and a series of 5-substituted cytosine analogues including
      all halogens. This set of oligonucleotides has been used to probe the
      relationship between the size of the substituent and its capacity to modulate
      cleavage by the methylation-sensitive restriction endonucleases MspI and HpaII.
      Additionally, we have examined the impact of the halogen substitution on the
      corresponding bacterial methyltransferase (M.HpaII). We observed that MspI
      cleavage is only subtly affected by substituted cytosine analogues at the inner
      position of the CCGG recognition site. In contrast, HpaII cleaves cytosine
      containing oligonucleotides completely whereas 5-fluorocytosine-containing
      oligonucleotides are cleaved at a reduced rate. The presence of the larger
      halogens Cl, Br, or I as well as a methyl group completely prevents cleavage by
      HpaII. These data suggest that the steric wall is encountered by HpaII slightly
      beyond the fluorine substituent, at about 2.65 A from the pyrimidine C5-position.
      It is known that 5-fluorocytosine in an oligonucleotide can form a covalent
      irreversible suicide complex with either prokaryotic or eukaryotic
      methyltransferases. Kinetic data reported here suggest that the 5-fluorocytosine
      containing oligonucleotide can also inhibit M.HpaII by formation of a reversible,
      noncovalent complex. Our results indicate that although a 5-Cl substituent has
      electronic properties similar to 5-F, 5-chlorocytosine duplexes neither form a
      complex with M.HpaII nor inhibit enzymatic methylation. Emerging data suggest
      that halogenation of cytosine can occur in DNA in vivo from inflammation-mediated
      reactive molecules. The results reported here suggest that the inadvertent
      halogenation of cytosine residues in DNA could alter the affinity of sequence
      specific DNA-binding proteins.

PMID- 16608166
TI  - Characterization of 1,2,3,4-diepoxybutane-2'-deoxyguanosine cross-linking
      products formed at physiological and nonphysiological conditions.
AB  - 1,2,3,4-Diepoxybutane (DEB), an in vivo metabolite of 1,3-butadiene (BD), is a
      carcinogen and mutagen. The strong carcinogenicity/mutagenicity of DEB has been
      attributed to its high DNA reactivity and cross-linking ability. Recently, we
      have demonstrated that under in vitro physiological conditions (pH 7.4, 37
      degrees C), the reaction of DEB with 2'-deoxyguanosine (dG) produced two
      diastereomeric pairs of the major nucleoside adducts resulting from alkylation at
      the N1- and N7-positions of dG, that is, 2'-deoxy-1-(2-hydroxy-2
      oxiranylethyl)guanosine and 2'-deoxy-7-(2-hydroxy-2-oxiranylethyl)guanosine,
      respectively [Zhang, X.-Y., and Elfarra, A. A. (2005) Chem. Res. Toxicol. 18,
      1316]. As each of these adducts contains an oxirane ring, the abilities of these
      adducts to form cross-linking products with dG under physiological conditions
      were investigated. Incubation of the N7 nucleoside adducts and their
      corresponding guanine product with dG led to formation of 7,7'-(2,3-dihydroxy-1,4
      butanediyl)bis[2-amino-1,7-dihydro-6H-purin-6-one] (bis-N7G-BD), a known DEB
      cross-linking product. Incubation of the N1 nucleoside adducts with dG led to
      formation of a pair of diastereomers of 2'-deoxy-1-[4-(2-amino-1,7-dihydro-6H
      purin-6-on-7-yl)-2,3-dihydroxybutyl]-guanosine (N7G-N1dG-BD), which are novel
      cross-linking products. Interestingly, the reaction of DEB with dG in glacial
      acetic acid at 60 degrees C yielded different cross-linking products, which were
      characterized as 2-amino-9-hydroxymethyl-4-{4-[2-amino-9- or 7-(4-acetyloxy-2,3
      dihydroxybutyl)-1,7-dihydro-6H-purin-6-on-7- or 9-yl]-2,3-dihydroxybutyl}-8,9
      dihydro-7H-[1,4]oxazepino[4,3,2-gh]purin-8-ol (PA2) and 9,9'-bis(4-acetyloxy-2,3
      dihydroxybutyl)-7,7'-(2,3-dihydroxy-1,4-butanediyl)bis[2-amino-1,7-dihydro-6H
      purin-6-one] (PA4). Collectively, these results increase our understanding of the
      chemical reactivity and cross-linking ability of DEB under both physiological and
      nonphysiological conditions.

PMID- 16608168
TI  - LC/MS/MS method for the quantitation of trans-2-hexenal-derived exocyclic 1,N(2)
      propanodeoxyguanosine in DNA.
AB  - trans-2-Hexenal is an alpha,beta-unsaturated aldehyde to which humans are exposed
      daily in small amounts. Hexenal has demonstrated mutagenicity and genotoxicity in
      vitro and reacts with deoxyguanosine to form diastereomeric hexenal-derived
      exocyclic 1,N(2)-propanodeoxyguanosine (Hex-PdG) adducts. A highly sensitive and
      specific method for the measurement of Hex-PdG in DNA has not previously been
      available. An LC/MS/MS assay for the quantitation of Hex-PdG, using
      [(13)C4(15)N2]Hex-PdG as an internal standard, was developed, to assess binding
      of hexenal to DNA. Samples were purified prior to analysis by centrifuge
      filtration and solid phase extraction and analyzed by LC/MS/MS in the selected
      reaction monitoring (SRM) mode (SRM m/z 366.2 --> 250.2 for Hex-PdG; SRM m/z
      372.2 --> 256.2 for [(13)C4(15)N2]Hex-PdG). Recovery of standards was 89% or
      greater, and quantitation was unaffected by the addition of increasing
      concentrations of calf thymus DNA (ctDNA). The limit of quantitation, determined
      in samples of 200 microg of ctDNA spiked with analyte standard, was 0.015
      fmol/microg DNA, which corresponds to approximately 5 Hex-PdG/10(9) unmodified
      nucleotides. Hex-PdG was detected in ctDNA treated with 0.021 microM, 0.21
      microM, or 2.1 mM hexenal but not in untreated DNA. Furthermore, Hex-PdG was not
      detected in DNA exposed to reactive oxygen species-mediated deoxyribose attack
      and lipid peroxidation, which resulted in a significant increase in the
      malondialdehyde-derived pyrimido[1,2-a]purin-10(3H)one. Hex-PdG was not detected
      in DNA of untreated rat liver, but Hex-PdG in hexenal-treated calf thymus DNA was
      quantifiable when spiked into the rat liver DNA at 0.035 or 0.35 fmol/microg DNA.
      These data indicate that Hex-PdG is formed following hexenal treatment and that
      this method is suitable for in vitro or in vivo assessment of Hex-PdG formation.

PMID- 16608169
TI  - Formation of acrolein adducts with 2'-deoxyadenosine in calf thymus DNA.
AB  - Acrolein is a ubiquitous environmental contaminant that has been found to be
      mutagenic in prokaryotic and eukaryotic cells. In the present study, we examined
      the reactions of acrolein with 2'-deoxyadenosine and calf thymus single- and
      double-stranded DNA in aqueous buffered solutions at physiological conditions.
      The deoxynucleoside adducts were isolated by reversed-phase liquid
      chromatography, and their structures were determined by their UV absorbance, mass
      spectrometry, and 1H and 13C NMR spectroscopy. The reaction of 2'-deoxyadenosine
      with acrolein resulted in the formation of four structurally different adducts
      (dAI, dAII, dAIII, dAIV). The structures of the novel acrolein adducts, dAIII and
      dAIV, were assigned as 3-[N(6)-(2'-deoxyadenosinyl)]propanal (dAIII) and 9-(2'
      deoxyribosyl-6-(3-formyl-1,2,5,6-tetrahydropyridyl)purine (dAIV), respectively.
      The adduct dAIII was found to arise via a Dimroth rearrangement of adduct dAI,
      while the adduct dAIV was shown to be formed upon further reaction of acrolein
      with dAIII. In the reaction of acrolein with calf thymus DNA, all studied 2'
      deoxyadenosine-acrolein adducts were observed. For the first time, it is shown
      that the N(6)-adduct and the adducts which are derived from two acrolein units
      are formed in calf thymus DNA.

PMID- 16608170
TI  - Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of
      aflatoxin B1.
AB  - The hepatic carcinogen aflatoxin B1 (AFB1) is metabolized in the liver by at
      least four different P450s, all of which exhibit large interindividual
      differences in the expression levels. These differences could affect the
      individual risk of hepatocellular carcinoma (HCC). We investigated the metabolism
      of AFB1 in a panel of 13 human liver microsomal preparations using a hepatic
      abundance model, which takes into account the specific kinetic parameters and the
      expression levels of these P450s. We found a 12-fold variability in the
      production rate of the carcinogenic metabolite AFB1-8,9-epoxide (AFBO) and a 22
      fold variability in the production of the detoxification product AFQ1. The ratio
      between the AFBO and the AFQ1 production rates varied between 1:19 and 1:1.7.
      P450 3A4 contributed a majority of AFBO and AFQ1, and its expression level was
      the most important determinant of the AFB1 disposition toward these primary
      metabolites. P450 3A5, which exclusively produced AFBO, was the second-most
      important enzyme activating AFB1 to AFBO, followed by P450 3A7 and P450 1A2. The
      relative contribution of AFBO by P450 3A5 strongly depended on the concomitant
      expression of P450 3A4, and it was as high as 15% in a P450 3A5 high expressor
      with the lowest P450 3A4 expression of all livers. The P450 1A2-specific AFB1
      detoxification product AFM1 was not detected. In conclusion, the variable
      expression of P450s has a major effect on the carcinogenic activation of AFB1,
      which may affect the individual predisposition to HCC. P450 3A4 expression is the
      most important determinant of AFB1 activation to AFBO. The contribution of P450
      1A2 to AFB1 metabolism appears to be negligible and may have been overestimated.
      Targeted chemoprevention of AFB1-associated HCC should consider P450 3A4
      inhibitors and avoidance of P450 3A4 inducers.

PMID- 16608171
TI  - Thiocyanate is an efficient endogenous scavenger of the phagocytic killing agent
      hypobromous acid.
AB  - Second-order rate constants for the reaction of HOBr/OBr- (a putative killing
      agent of eosinophils and a reactive oxygen species that is implicated in
      mutagenesis and in human inflammatory diseases) with SCN- (an endogenous species
      in human physiologic fluids) are determined by stopped-flow spectroscopy. The
      proposed mechanism includes parallel pathways with Br+ transfer to SCN- by
      general acid catalysis and by direct reaction with HOBr. HOBr reacts with SCN-
      with a second-order rate constant (2.3 x 10(9) M(-1) s(-1)) that is 2 orders of
      magnitude larger than that previously measured for the reaction of HOCl with SCN-
      (2.3 x 10(7) M(-1) s(-1)), and very close to the diffusion limit. In contrast to
      OCl-, OBr- exhibits a measurable rate of reaction with SCN- (3.8 x 10(4) M(-1) s(
      1)). On a molar basis, SCN- is the most effective scavenger of HOBr to be
      reported to date (200 times more effective than cysteine and 650 times more
      effective than methionine). Computational models suggest that SCN- is competitive
      with respect to other scavengers at physiologically relevant concentrations,
      which leads us to propose it may limit the lifetime of HOBr and its propensity to
      inflict host tissue damage during inflammatory response, especially during
      eosinophilia. Furthermore, the product of the nonenzymatic reaction of HOBr and
      SCN-, hypothiocyanite (OSCN-), is an effective antimicrobial that is relatively
      innocuous toward mammalian cell lines. Since one of the principal charges of
      eosinophil cells is to clear extracellular parasites via nonphagocytic mechanisms
      that involve degranulation of eosinophil peroxidase (EPO, the principal mammalian
      enzyme that produces HOBr), a larger role for OSCN- is suggested for parasitic
      infection.

PMID- 16608172
TI  - Ester hydrolysis and nitrosative deamination of novocaine in aqueous solutions.
AB  - In aqueous solutions, the kinetic features of both the hydrolysis reaction of the
      ester function of novocaine in alkaline medium and the nitrosation reaction of
      the primary amine group of novocaine in mild acid medium were investigated by
      UV/vis spectroscopy. The ester hydrolysis shows first-order kinetics with respect
      to both the drug and the nucleophile, OH-, concentrations, thus following a
      typical S(N)2 (Ac) mechanism. The rate of the reaction decreases strongly with
      the polarity of the reaction media, analyzed for both dioxane-water and Me2SO
      water mixtures. The effect of the presence of cationic micelles of
      tetradecyltrimethylammonium bromide, TTABr, was abnormal in that it inhibits the
      rate of the reaction throughout the analyzed concentration range of the
      surfactant. The same pattern of behavior is observed in the presence of anionic
      micelles of sodium dodecyl sulfate (SDS); however, the effect is more pronounced.
      The rate equation obtained in the kinetic study of the nitrosation reaction of
      novocaine in mild acid medium contains first- and second-order terms with respect
      to [nitrite], which correspond with the two parallel reaction paths due to
      nitrosation via both NO+ and N2O3, respectively; the rate of the reaction also
      increases with both the [H+] and the total acetic acid-acetate buffer
      concentration. In contrast to the ester hydrolysis, the nitrosation reaction is
      accelerated in aqueous micellar solutions of both cationic and anionic
      surfactants of TTABr and SDS, respectively.

PMID- 16608175
TI  - Sum-frequency vibrational spectroscopy on water interfaces: polar orientation of
      water molecules at interfaces.

PMID- 16608173
TI  - The seleno bis(S-glutathionyl) arsinium ion is assembled in erythrocyte lysate.
AB  - Approximately 75 million people are currently exposed to arsenic concentrations
      in drinking water, which is associated with the development of internal cancers.
      One way to ameliorate this undesirable situation is to remove arsenic (arsenite
      and arsenate) from drinking water. An alternative approach is the development of
      an inexpensive palliative dietary supplement that promotes the excretion of
      intestinally absorbed arsenite from the body. To this end, the simultaneous
      administration of New Zealand white rabbits with arsenite and selenite resulted
      in the biliary excretion of the seleno-bis (S-glutathionyl) arsinium ion,
      [(GS)2AsSe]-. This apparent detoxification mechanism has been recently extended
      to environmentally relevant doses [Gailer, J., Ruprecht, L., Reitmeir, P.,
      Benker, B., and Schramel, P. (2004) Appl. Organometal. Chem. 18, 670-675]. The
      site of formation of this excretory product in the organism, however, is unknown.
      To investigate if [(GS)2AsSe]- is formed in rabbit blood, we added arsenite and
      selenite and analyzed blood aliquots using arsenic and selenium X-ray absorption
      spectroscopy. The characteristic arsenic and selenium X-ray absorption spectra of
      [(GS)2AsSe]- were detected within 2 min after addition and comprised 95% of the
      blood selenium 30 min after addition. To elucidate if erythrocytes are involved
      in the biosynthesis of [(GS)2AsSe]- in blood, arsenite and 77Se-selenite were
      added to rabbit erythrocyte lysate and the obtained solution was analyzed by 77Se
      NMR spectroscopy (273 K). This resulted in a 77Se NMR signal with a chemical
      shift identical to that of synthetic [(GS)2AsSe]- added to lysate. Combined,
      these results demonstrate that [(GS)2AsSe]- is rapidly formed in blood and that
      erythrocytes are an important site for the in vivo formation of this
      toxicologically important metabolite.

PMID- 16608176
TI  - Vibrational spectroscopic studies of aqueous interfaces: salts, acids, bases, and
      nanodrops.

PMID- 16608177
TI  - Photoemission from liquid aqueous solutions.

PMID- 16608178
TI  - Static and dynamic electronic spectroscopy at liquid interfaces.

PMID- 16608179
TI  - Theoretical modeling of interface specific vibrational spectroscopy: methods and
      applications to aqueous interfaces.

PMID- 16608180
TI  - Specific ion effects at the air/water interface.

PMID- 16608181
TI  - First-principles approaches to the structure and reactivity of atmospherically
      relevant aqueous interfaces.

PMID- 16608182
TI  - Recent advances in molecular simulations of ion solvation at liquid interfaces.

PMID- 16608183
TI  - Mass accommodation and chemical reactions at gas-liquid interfaces.

PMID- 16608184
TI  - Molecular simulations of the transport of molecules across the liquid/vapor
      interface of water.

PMID- 16608185
TI  - The uptake of acidic gases on ice.

PMID- 16608187
TI  - Second harmonic spectroscopy of aqueous nano- and microparticle interfaces.

PMID- 16608186
TI  - The influence of organic films at the air-aqueous boundary on atmospheric
      processes.

PMID- 16608188
TI  - Molecular structure of water at interfaces: wetting at the nanometer scale.

PMID- 16608189
TI  - Ambient thin film water on insulator surfaces.

PMID- 16608190
TI  - Aqueous solutions next to phospholipid membrane surfaces: insights from
      simulations.

PMID- 16608192
TI  - Coherence between legal requirements and approaches for detection of genetically
      modified organisms (GMOs) and their derived products.
AB  - Analytical methods for the qualitative and quantitative detection of genetically
      modified (GM) products may serve multiple purposes. Legal requirements differ
      among jurisdictions, ranging from no requirements to mandatory use of event
      specific quantitation and implementation of production chain traceability.
      Although efforts have been taken to harmonize the analytical methodology at
      national, regional, and international levels, no normative international
      standards have yet been established. Lack of coherence between analytical
      methodologies and their applicabilities, on the one hand, and legislation, on the
      other hand, is a major problem. Here, key points where coherence is lacking are
      discussed. These include the definition of units of measurements, expression of
      GM material quantities, terminology, and inconsistent legal status of products
      derived from related but slightly different transformation routes. Finally,
      recommendations to improve the coherence are brought forward, including guidance
      to stakeholders for prediction of product-specific GM material quantities from
      gene ratios in the originating seed.

PMID- 16608193
TI  - Comparison of the HPLC method and FT-NIR analysis for quantification of glucose,
      fructose, and sucrose in intact apple fruits.
AB  - A rapid quantification method was developed and validated for simultaneous and
      nondestructive quantifying the constituent sugar concentrations of intact apples
      using Fourier transform near-infrared (FT-NIR) spectroscopy in diffuse
      reflectance mode. Multiplicative scatter correction (MSC), the second derivative
      of Savitsky-Golay, and mean centering were used as spectral preprocessing
      options. Calibration models were established by the partial least squares (PLS)
      regression analysis, and validation of the method was performed according to the
      high-performance liquid chromatography (HPLC) chromatographic method. Spectral
      range and the number of PLS factors were optimized for the lowest root-mean
      square error of prediction (RMSEP) and correlation coefficient of determination
      (r). The best models showed satisfactory predictions as measured by the RMSEP and
      r values: glucose, 0.201 and 0.950; fructose, 0.298 and 0.968; sucrose, 0.335 and
      0.969, respectively. FT-NIR analysis of constituent sugar concentrations in the
      intact apple form was found to be more flexible and much faster than performed
      with the HPLC method.

PMID- 16608194
TI  - High-performance liquid chromatographic method for the quantitative determination
      of Hypoxoside in African potato (Hypoxis hemerocallidea) and in commercial
      products containing the plant material and/or its extracts.
AB  - Hypoxoside is a norlignan diglucoside present in the corms of African potato
      (Hypoxis hemerocallidea). The latter is used as a popular African traditional
      medicine for it's nutritional and immune-boosting properties. A reverse phase
      high-performance liquid chromatography method was developed and validated for the
      determination of hypoxoside using a mobile phase consisting of acetonitrile:water
      (20:80, v/v). The method was linear throughout the range of 10-100 microg/mL and
      provided a high degree of accuracy (100 +/- 4%). The recovery of the method was
      found to be 100 +/- 5%, and the precision of the study, % relative standard
      deviation intraday and interday (over three separate days), was better than 6.15
      and 5.64%, respectively. The limits of detection and quantification were
      calculated to be 0.75 and 3.5 microg/mL, respectively. This method was applied to
      the analysis and quality control of African potato corms as well as 12
      commercially available products. The daily intake of hypoxoside through
      traditionally prepared African potato decoction was also evaluated.

PMID- 16608195
TI  - Simultaneous determination of (fluoro)quinolone antibiotics in kidney, marine
      products, eggs, and muscle by enzyme-linked immunosorbent assay (ELISA).
AB  - A direct competitive enzyme-linked immunosorbent assay (ELISA) was developed to
      detect a broad range of (fluoro)quinolones in various matrices. In the optimized
      generic test, anti-sarafloxacin antibodies in combination with norfloxacin
      conjugate showed 50% binding inhibition at 0.21 ng mL(-)(1) for sarafloxacin in
      buffer. Screening for this class of antibiotics is accomplished using a simple,
      rapid extraction carried out with a 1:1 mixture of methanol and phosphate
      buffered saline adjusted to pH 7.4. This common extraction was able to detect 15
      (fluoro)quinolone residues such as sarafloxacin, norfloxacin, difloxacin,
      ciprofloxacin, pefloxacin, ofloxacin, cinoxacin, danofloxacin, enrofloxacin,
      marbofloxacin, lomefloxacin, enoxacin, flumequine, oxolinic acid, and nalidixic
      acid in pig kidney, poultry muscle, egg, fish, and shrimp. The assay's detection
      capabilities (CCbeta) for most of these compounds were <10 microg kg(-)(1) except
      for the sarafloxacin-, oxolinic acid-, flumequine-, and cinoxacin-spiked
      matrices, the estimated CCbeta values of which were <4, <25, <100, and <200
      microg kg(-)(1), respectively.

PMID- 16608196
TI  - Electrofocusing of methanolic extracts for identification of individual flavonol
      biomolecules in Camellia species.
AB  - An effort has been made to isolate individual catechin compounds from green tea
      leaves in their pure form by electrophoresis. In the present study total
      polyphenol extraction was carried out initially and estimated through
      spectrophotometric and HPLC methods. Extracted polyphenol was separated on 0.7%
      agarose gel and visualized at 360 nm. Fragmented individual compounds were gel
      eluted with methanol and confirmed as (-)-epigallocatechin (EGC), (-)-epicatechin
      (EC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG) by
      HPLC. The method developed describes a suitable method for the isolation of
      valuable molecules in tea.

PMID- 16608197
TI  - Evaluation of phenolic compounds in virgin olive oil by direct injection in high
      performance liquid chromatography with fluorometric detection.
AB  - Hydrophilic phenols are the most abundant natural antioxidants of virgin olive
      oil (VOO), in which tocopherols and carotenes are also present. The prevalent
      classes of hydrophilic phenols found in VOO are phenyl alcohols, phenolic acids,
      secoiridoids such as the dialdehydic form of decarboxymethyl elenolic acid linked
      to (3,4-dihydroxyphenyl)ethanol or (p-hydroxypheny1)ethanol (3,4-DHPEA-EDA or p
      HPEA-EDA) and an isomer of the oleuropein aglycon (3,4-DHPEA-EA), lignans such as
      (+)-1-acetoxypinoresinol and (+)-pinoresinol, and flavonoids. A new method for
      the analysis of VOO hydrophilic phenols by direct injection in high-performance
      liquid chromatography (HPLC) with the use of a fluorescence detector (FLD) has
      been proposed and compared with the traditional liquid-liquid extraction
      technique followed by the HPLC analysis utilizing a diode array detector (DAD)
      and a FLD. Results show that the most important classes of phenolic compounds
      occurring in VOO can be evaluated using HPLC direct injection. The efficiency of
      the new method, as compared to the liquid-liquid extraction, was higher to
      quantify phenyl alcohols, lignans, and 3,4-DHPEA-EA and lower for the evaluation
      of 3,4-DHPEA-EDA and p-HPEA-EDA.

PMID- 16608198
TI  - A simple method to separate red wine nonpolymeric and polymeric phenols by solid
      phase extraction.
AB  - Simple polyphenols and tannins differ in the way that they contribute to the
      organoleptic profile of wine and their effects on human health. Very few
      straightforward techniques to separate red wine nonpolymeric phenols from the
      polymeric fraction are available in the literature. In general, they are complex,
      time-consuming, and generate large amounts of waste. In this procedure, the
      separation of these compounds was achieved using C18 cartridges, three solvents
      with different elution strengths, and pH adjustments of the experimental
      matrices. Two full factorial 2(3) experimental designs were performed to find the
      optimal critical variables and their values, allowing for the maximization of
      tannin recovery and separation efficiency (SE). Nonpolymeric phenols such as
      phenolic acids, monomers, and oligomers of flavonol and flavan-3-ols and
      anthocyanins were removed from the column by means of an aqueous solvent followed
      by ethyl acetate. The polymeric fraction was then eluted with a combination of
      methanol/acetone/water. The best results were attained with 1 mL of wine sample,
      a 10% methanol/water solution (first eluant), ethyl acetate (second eluant), and
      66% acetone/water as the polymeric phenols-eluting solution (third eluant),
      obtaining a SE of ca. 90%. Trials with this method on fruit juices also showed
      high separation efficiency. Hence, this solid-phase extraction method has been
      shown to be a simple and efficient alternative for the separation of nonpolymeric
      phenolic fractions and the polymeric ones, and this method could have important
      applications to sample purification prior to biological testing due to the
      nonspecific binding of polymeric phenolics to nearly all enzymes and receptor
      sites.

PMID- 16608199
TI  - Improved method for the determination of hydroxymethylfurfural in baby foods
      using liquid chromatography-mass spectrometry.
AB  - An improved analytical method for the rapid, reliable, and sensitive
      determination of hydroxymethylfurfural (HMF) in baby foods is described. It
      entailed aqueous extraction from food matrix with simultaneous clarification
      using Carrez I and II reagents, solid-phase extraction cleanup using Oasis HLB,
      and analysis by liquid chromatography-mass spectrometry. A narrow-bore column
      allowed fast chromatographic separation with good resolution of HMF and matrix
      coextractives. In positive atmospheric pressure chemical ionization conditions,
      precursor and compound-specific ions were sensitively detected in selected ion
      monitoring mode. Sample preparation with efficient cleanup followed by fast
      chromatographic analysis allowed the analysis to be completed in <20 min.
      Recovery ranged between 91.8 and 94.7% for spiking levels of 0.25, 1.0, and 5.0
      mg/kg HMF in cereal-based baby foods. The method was shown to be successful when
      using liquid chromatography coupled to ultraviolet detection at 285 nm.

PMID- 16608200
TI  - Application of stable carbon isotope analysis to the detection of testosterone
      administration to cattle.
AB  - The use of anabolic substances is prohibited in food-producing animals throughout
      the European Union. No method is available to reliably detect the misuse of
      natural hormones in cattle. A method was developed to detect the abuse of
      testosterone in cattle fattening. Synthesized testosterone is rather depleted in
      the (13)C/(12)C ratio. Hence, the method is based on gas
      chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analysis of
      urine. To select testosterone metabolites and endogenous reference compounds
      (ERC), the concentration of urinary steroids of cattle was investigated.
      Dehydroepiandrosterone and androst-5ene-3beta,17alpha-diol were chosen as ERCs to
      show endogenous (13)C/(12)C ratios. Etiocholanolone and 5alpha-androstane
      3beta,17alpha-diol were chosen as the most important testosterone metabolites.
      Other metabolites known from literature like epitestosterone were less promising.
      In principle, GC/C/IRMS is a nonspecific method because finally carbon dioxide is
      analyzed. Therefore, a dedicated cleanup procedure for the selected steroids was
      developed. By means of proposed confidence intervals in the isotopic composition
      of ERCs and metabolites, the administration of testosterone to cattle could be
      detected reliably. Differences of up to 11 per thousand on the delta-scale
      between ERC and testosterone metabolites were found after testosterone
      administration, whereas endogenous differences did not exceed 2 per thousand.

PMID- 16608201
TI  - Quantitative analysis of N-phenylpropenoyl-L-amino acids in roasted coffee and
      cocoa powder by means of a stable isotope dilution assay.
AB  - Since recent reports on the role of N-phenylpropenoyl-L-amino acids as powerful
      antioxidants and key contributors to the astringent taste of cocoa nibs, there is
      an increasing interest in the concentrations of these phytochemicals in plant
      derived foods. A versatile analytical method for the accurate quantitative
      analysis of N-phenylpropenoyl-L-amino acids in plant-derived foods by means of
      HPLC-MS/MS and synthetic stable isotope labeled N-phenylpropenoyl-L-amino acids
      as internal standards was developed. By means of the developed stable isotope
      dilution assay (SIDA), showing recovery rates of 95-102%, 14 N-phenylpropenoyl-L
      amino acids were quantified for the first time in cocoa and coffee samples. On
      the basis of the results of LC-MS/MS experiments as well as cochromatography with
      the synthetic reference compounds N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tryptophan,
      N-[4'-hydroxy-(E)-cinnamoyl]-L-tryptophan, and N-[4'-hydroxy-3'-methoxy-(E)
      cinnamoyl]-L-tyrosine, respectively, were detected for the first time in cocoa
      powder, and (-)-N-[4'-hydroxy-(E)-cinnamoyl]-L-tyrosine, (-)-N-[3',4'-dihydroxy
      (E)-cinnamoyl]-L-tyrosine, N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]-L-tyrosine,
      (+)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-aspartic acid, (+)-N-[4'-hydroxy-(E)
      cinnamoyl]-L-aspartic acid, N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tryptophan, N-[4'
      hydroxy-(E)-cinnamoyl]-L-tryptophan, and N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]
      L-tryptophan, respectively, were detected for the first time in coffee beverages.

PMID- 16608202
TI  - Solid phase extraction of Cd, Cu, and Ni from leafy vegetables and plant leaves
      using amberlite XAD-2 functionalized with 2-hydroxy-acetophenone
      thiosemicarbazone (HAPTSC) and determination by inductively coupled plasma atomic
      emission spectroscopy.
AB  - A method for solid phase extraction of trace metals, namely, Cd, Cu, and Ni,
      using Amberlite XAD-2 functionalized with a new chelating ligand, 2-hydroxy
      acetophenone-3-thiosemicarbazone (Amberlite XAD-2-HAPTSC), has been developed.
      The optimum experimental conditions for the quantitative sorption of three
      metals, pH, effect of flow rate, concentration of eluent, sorption capacity,
      kinetics of sorption, and the effect of diverse ions on the sorption of analytes
      have been investigated. The chelating resin could be reused for more than 20
      cycles of sorption-desorption without any significant change (<1.5%). The
      accuracy of the proposed procedure was evaluated by standard reference materials.
      The proposed method was applied for the determination of trace metal ions in
      leafy vegetable samples collected from different sources and medicinal plant
      leaves.

PMID- 16608203
TI  - Determination of five macrolide antibiotic residues in raw milk using liquid
      chromatography-electrospray ionization tandem mass spectrometry.
AB  - A confirmatory method using liquid chromatography-electrospray ionization tandem
      mass spectrometry for determination of five macrolide antibiotics including
      spiramycin, tilmicosin, oleandomycin, erythromycin, and tylosin in raw milk is
      presented. Macrolides were extracted from raw milk by acetonitrile, and sample
      extracts were further cleaned up using solid-phase extraction cartridges. Data
      acquisition was achieved using multiple reaction monitoring, that is, two
      transitions, to provide a high degree of sensitivity and specificity. Matrix
      matched standard calibration curves with the use of roxithromycin as an internal
      standard were utilized to achieve the best accuracy of the method. Both a
      conventional validation procedure and a designed experiment were applied to study
      the accuracy and precision of the method. The measurement uncertainty arising
      from accuracy and precision was estimated. The method accuracy, expressed as a
      percentage of overall recovery, was approximately 100%, and its intermediate
      precision was <10%. LC-ESI/MS/MS method detection limits (S/N > or = 3:1) of five
      macrolides were <0.3 microg/kg.

PMID- 16608204
TI  - Evaluation of the light-sensitive cytotoxicity of Hypericum perforatum extracts,
      fractions, and pure compounds.
AB  - Hypericum perforatum (Hp) is known for possessing antidepressant and antiviral
      activities. Despite its use as an alternative to conventional antidepressants,
      the identification of the cytotoxic chemicals derived from this herb is
      incomplete. In this study, the cytotoxicity of Hp extracts prepared in solvents
      ranging in polarity, fractions of one extract, and purified compounds were
      examined in three cell lines. All extracts exhibited significant cytotoxicity;
      those prepared in ethanol (no hyperforin, 3.6 microM hypericin, and 134.6 microM
      flavonoids) showed between 7.7 and 77.4% cell survival (p < 0.0001 and 0.01),
      whereas the chloroform and hexane extracts (hyperforin, hypericin, and flavonoids
      not detected) showed approximately 9.0 (p < 0.0001) and 4.0% (p < 0.0001)
      survival. Light-sensitive toxicity was observed primarily with the ethanol
      extracts sequentially extracted following removal of material extracted in either
      chloroform or hexane. The absence of light-sensitive toxicity with the Hp
      extracts suggests that the hypericins were not playing a prominent role in the
      toxicity of the extracts.

PMID- 16608205
TI  - Salicylic acid content of spices and its implications.
AB  - This work was done to determine the salicylate content of a variety of commonly
      used spices and to assess whether this potential dietary source of salicylate was
      bioavailable. Spices, Indian cooked dishes, and blood and urine samples taken
      after ingestion of a test meal were investigated for their salicylate content
      using high-performance liquid chromatography with electrochemical detection. The
      serum salicylic acid concentrations in samples from villagers in southern India
      were also measured and have been compared with typical European values. Salicylic
      acid was determined in all spices (up to 1.5 wt %) and cooked dishes. The
      salicylate content of blood and urine was shown to increase following consumption
      of the meal, indicating that this dietary source of salicylic acid was
      bioavailable. Salicylic acid levels in the serum from rural Indians were
      significantly (median almost 3-fold) higher than values previously measured in
      Western vegetarians. Chemoprotective aspirin is rapidly hydrolyzed to salicylic
      acid, and this phytochemical may contribute to the low cancer incidence in rural
      India.

PMID- 16608206
TI  - Unravelling the total antioxidant capacity of pinotage wines: contribution of
      phenolic compounds.
AB  - The total antioxidant capacity (TAC) and phenolic composition of 139 Pinotage
      wines (2002 and 2003 vintages) were determined using the 2,2'-azino-di(3
      ethylbenzo-thialozine-sulfonic acid) scavenging assay and high-performance liquid
      chromatography, respectively. The contribution of individually quantified
      phenolic compounds to the wine TAC was calculated using their concentrations and
      Trolox equivalent antioxidant capacity (TEAC) values. The TEAC values of
      quercetin-3-galactoside, isorhamnetin, and peonidin-3-glucoside are reported for
      the first time. Between 11 and 24% of the measured TAC of Pinotage wines was
      explained by the sum of the calculated contributions of their quantified phenolic
      compounds comprising monomeric phenolic compounds and procyanidin B1.
      Ultrafiltration was carried out to attempt separation of monomeric and polymeric
      phenolic compounds. Analysis of ultrafiltration permeates and retentates enabled
      estimation of the TAC contribution of large molecular weight (MW) unknown
      compounds (46%) (>50 kDa), including oligomeric and polymeric phenolic compounds
      and small MW unknown compounds (34%) (<50 kDa). Three mixtures, containing 12
      phenolic compounds in typical concentrations expected in Pinotage wines,
      exhibited 16-23% synergistic antioxidant activity. This suggests that synergy
      between phenolic compounds does play a role in the wine TAC but that it does not
      explain the large discrepancy between measured and calculated TAC values.

PMID- 16608207
TI  - Immunomodulatory properties of Grifola frondosa in submerged culture.
AB  - Maitake (Grifola frondosa) is a popular mushroom in Asia for its tasty flavor and
      immune-stimulating property. The aim of the study is to investigate the innate
      immunity augmentation effects of different extracts of mycelia and culture
      filtrate from G. frondosa in submerged cultures. The hot water extract of mycelia
      showed the strongest cytokine induction effect as a function of its concentration
      in human whole blood culture. The most potent fractions of hot water extract, Fr.
      I and II, were mainly composed of polysaccharides with molecular masses of 43-140
      and 13-38 kDa, respectively. These fractions (0.025 mg/mL) showed marked activity
      in enhancing phagocytosis of human polymorphonuclear neutrophils (PMN). In
      parallel, the expression of CD11b, an early marker of PMN activation, was also up
      regulated dose dependently. This result suggested that complement receptor 3 was
      primed by these fractions. In addition to activation of phagocytes, these
      bioactive fractions also increased human peripheral blood natural killer cell
      cytotoxicity. These results imply that the relatively low molecular mass
      polysaccharides isolated from mycelia of G. frondosa can enhance innate immunity
      in vitro and therefore may serve as biological response modifiers.

PMID- 16608208
TI  - Anti type I allergic property of Japanese butterbur extract and its mast cell
      degranulation inhibitory ingredients.
AB  - Pollenosis is a disease that affects 1 in 10 of the Japanese population. During
      the season of cedar pollen dispersal, many patients suffer from symptoms such as
      sniffling, sternutation, and itching of the eyes. Japanese butterbur is a popular
      vegetable and is one of the few domestic vegetables in Japan. The anti type I
      allergic effects of an aqueous ethanol extract from aerial parts of Japanese
      butterbur (JBE) were evaluated in rats and RBL-2H3 mast cells. In the passive
      cutaneous anaphylaxis reaction in rats, a single oral treatment of JBE (1000
      mg/kg) was found to suppress the reaction. In IgE-sensitized RBL-2H3 cells, JBE
      (10-100 microg/mL) inhibited beta-hexosaminidase release, leukotriene
      C(4)/D(4)/E(4) synthesis, and TNF-alpha production. Moreover, a high
      concentration of JBE (1000 microg/mL) suppressed smooth muscle constriction
      induced by histamine (10 microM) and leukotriene D(4) (10 nM) in a guinea pig
      trachea strip. The search for components in JBE with an inhibitory activity on
      mast cell degranulation was guided by inhibition of beta-hexsosaminidase release.
      Two eremophilane-type sesquiterpenes, six polyphenolic compounds, and two
      triterpene glycosides were isolated. Of these compounds, fukinolic acid, a
      principal polyphenol constituent, showed potent inhibitory activity (IC(50) value
      = 2.1 microg/mL). Consequently, On the basis of its inhibition of mast cell
      activation and direct smooth muscle reaction induced by released mediators, JBE
      was found to suppress the type I allergic reaction.

PMID- 16608209
TI  - Insecticidal activity of Paraherquamides, including paraherquamide H and
      paraherquamide I, two new alkaloids isolated from Penicillium cluniae.
AB  - Paraherquamide H (1) and paraherquamide I (2), two new compounds of the
      paraherquamide (PHQ) family, together with the already known paraherquamide A
      (3), paraherquamide B (4), paraherquamide E (5), VM55596 (N-oxide paraherquamide)
      (6), paraherquamide VM55597 (7), and five known diketopiperazines (8-12) have
      been isolated from the culture broth of Penicillium cluniae Quintanilla. The
      structure of 1 and 2, on the basis of NMR and MS analysis, was established. It is
      worth noticing that, in both cases, an unusual oxidative substitution in C-16 was
      found, which had only previously been detected in PHQ 7. Isolated compounds were
      tested for insecticidal activity against the hemipteran Oncopeltus fasciatus
      Dallas. Mortality data have allowed preliminary structure activity relationships
      to be proposed. The most potent product was 5 with a LD(50) of 0.089
      microg/nymph.

PMID- 16608210
TI  - Antioxidant activity of isoflavones and their major metabolites using different
      in vitro assays.
AB  - Isoflavone phytoestrogens found mainly in soybeans and clover are widely studied
      phytochemicals. Genistein and daidzein, the major isoflavones found in soy, have
      received the most attention. However, they undergo extensive metabolism in the
      intestine and the liver, which might affect their biological properties, e.g.
      their antioxidant capacities. Furthermore, the biological activities of other
      naturally occurring isoflavones, for instance, glycitein from soy or biochanin A
      from red clover, have not yet been studied in detail. The aim of this study was
      to investigate the antioxidant activities of six naturally occurring isoflavones
      and their corresponding oxidative and bacterial metabolites. The oxygen radical
      absorbance capacity assay as well as the in vitro oxidation of low density
      lipoproteins with the conjugated diene and the thiobarbituric acid reacting
      substances formation as end points were used. The oxidative metabolites of
      genistein and daidzein as well as equol exhibited the highest antioxidant
      activities in all three assays. With few exceptions, they were more effective
      than the positive controls quercetin and ascorbic acid. Formononetin, the 4'-O
      methyl ether of daidzein, showed the lowest antioxidant property. Because the
      antioxidant efficacy of isoflavones as effective antioxidants is evident at
      concentrations well within the range found in the plasma of subjects consuming
      soy products, this biological activity could be of physiological relevance.

PMID- 16608211
TI  - Solvent and pH effects on the antioxidant activity of caffeic and other phenolic
      acids.
AB  - The antioxidant activity of several phenolic acids and esters has been
      investigated both in organic solutions and in large unilamellar
      phosphatidylcholine vesicles. In solution these compounds behaved as good
      antioxidants, with the exception of protocatechuic acid, due to the presence of
      the catechol moiety. Because their antioxidant activity followed an inverse
      dependence on the magnitude of their O-H bond dissociation enthalpies (BDE), the
      key mechanism of the chain-breaking action was attributed to hydrogen atom
      transfer (HAT) from the phenolic OH to peroxyl radicals. In unilamellar vesicles
      the antioxidant activity was strongly dependent on the pH of the buffer solution.
      In acid media (pH 4) all of the examined phenolic acids or esters behaved as weak
      inhibitors of peroxidation, whereas, with increasing pH, their antioxidant
      activity increased substantially, becoming comparable to or even better than that
      of Trolox. At pH 8 they also gave rise to lag phases 2-3 times longer than that
      of Trolox. The increased activity being observed in proximity of the pK(a) value
      corresponding to the ionization of one of the catecholic hydroxyl groups, this
      effect has been attributed to the high antioxidant activity of the phenolate
      anion.

PMID- 16608212
TI  - Effect of hop (Humulus lupulus L.) flavonoids on aromatase (estrogen synthase)
      activity.
AB  - The aim of this work was to study the effect of the prenylflavonoids xanthohumol,
      isoxanthohumol, and 8-prenylnaringenin on the activity and expression of the
      enzyme aromatase (estrogen synthase). The effect of different kinds of beer
      containing these prenylflavonoids was also tested. Aromatase activity was
      determined by measuring the release of tritiated water during the conversion of
      [(3)H]androstenedione to estrone. Aromatase expression was determined by RT-PCR.
      This assay was carried out in choriocarcinoma-derived JAR cells. The tested
      prenylflavonoids were able to inhibit estrogen formation, and their IC(50) values
      were determined, although no effect on aromatase expression was found. Lager
      beer, alcohol-free beer, stout beer, and xanthohumol-rich stout beer (200
      microL/mL) significantly decreased aromatase activity. In conclusion,
      prenylflavonoids are able to modulate aromatase activity, decreasing estrogen
      synthesis, with relevance for the prevention and treatment of estrogen-dependent
      disorders such as breast cancer.

PMID- 16608213
TI  - Gastrointestinal absorption and urinary excretion of trans-cinnamic and p
      coumaric acids in rats.
AB  - trans-Cinnamic acid (CIN) and p-coumaric acid (COU) are ingested by humans in
      their diet. While the metabolism and health benefits of CIN have been widely
      documented, little is known about its absorption sites, and there have been few
      studies dedicated to COU. The gastrointestinal sac technique demonstrated that
      CIN and COU are absorbed by all digestive organs in rats and partially
      transported via MCT-mediated carrier. Absorption was lowest in the stomach.
      Regardless of the organs that were studied, CIN was more efficiently absorbed
      than COU. After their individual oral administration to rats, CIN and COU were
      excreted in 0-24 h urine (0.3% and 23% of ingested CIN and COU, respectively).
      This suggests that COU was less metabolized than CIN. CIN and COU are absorbed
      across the digestive epithelium and subsequently interact with target tissues.
      Despite its lower gastrointestinal absorption, COU may have greater health
      benefits because it seems to be less metabolized than CIN.

PMID- 16608214
TI  - Enzymatic preparation of kaempferol from green tea seed and its antioxidant
      activity.
AB  - Among the flavonols in green tea, kaempferol has many biological activities but
      kaempferol of plant origin is too expensive to be used in commercial products.
      Recently, we confirmed that green tea seed (GTS) contained a reasonable amount of
      kaempferol glycoside. After conducting structure analysis, two kaempferol
      glycosides were identified, kaempferol-3-O-[2-O-beta-D-galactopyranosyl-6-O-alpha
      L-rhamnopyranosyl]-beta-D-glucopyranoside (compound 1) and kaempferol-3-O-[2-O
      beta-D-xylopyranosyl-6-O-alpha-L-rhamnopyranosyl]-beta-D-glucopyranoside
      (compound 2), respectively. Also, a commercially useful method for kaempferol
      preparation was suggested by enzymatic hydrolysis using these two flavonoids.
      After several enzyme reactions were performed for the complete bioconversion of
      compounds 1 and 2 to kaempferol, we found that the optimum enzyme combination was
      reaction with beta-galactosidase and hesperidinase. Finally, we produced pure
      kaempferol with over 95% purity. We also compared the antioxidant effect of these
      two GTS flavonoids and its aglycone, kaempferol. Kaempferol is a more efficient
      scavenger of 1,1-diphenyl-2-picrylhydrazyl radicals and a better inhibitor of
      xanthine/xanthine oxidase than the two glycosides.

PMID- 16608215
TI  - Dialkyl 3,3'-thiodipropionate and dialkyl 2,2'-thiodiacetate antioxidants by
      lipase-catalyzed esterification and transesterification.
AB  - Medium- and long-chain dialkyl 3,3'-thiodipropionate antioxidants such as dioctyl
      3,3'-thiodipropionate, didodecyl 3,3'-thiodipropionate, dihexadecyl 3,3'
      thiodipropionate, and di-(cis-9-octadecenyl) 3,3'-thiodipropionate were prepared
      in high yield by lipase-catalyzed esterification and transesterification of 3,3'
      thiodipropionic acid and its dimethyl ester, respectively, with the corresponding
      medium- or long-chain 1-alkanols, i.e., 1-octanol, 1-dodecanol, 1-hexadecanol,
      and cis-9-octadecen-1-ol, in vacuo (80 kPa) at moderate temperatures (60-80
      degrees C) without solvents. Immobilized lipase B from Candida antarctica
      (Novozym 435) was the most active biocatalyst for the preparation of medium- and
      long-chain dialkyl 3,3'-thiodipropionates showing enzyme activities up to 1489
      units/g, whereas the immobilized lipases from Rhizomucor miehei (Lipozyme RM IM)
      and Thermomyces lanuginosus (Lipozyme TL IM) were by far less active (
      approximately 10 enzyme units/g). Maximum conversions to dialkyl 3,3'
      thiodipropionates were as high as 92-98% after 4 h of reaction time. Similarly,
      dihexadecyl 2,2'-thiodiacetate was prepared in high yield using 2,2'-thiodiacetic
      acid or diethyl 2,2'-thiodiacetate and 1-hexadecanol as the starting materials
      and Novozym 435 as the biocatalyst.

PMID- 16608216
TI  - Beet sugar syrup and molasses as low-cost feedstock for the enzymatic production
      of fructo-oligosaccharides.
AB  - Sugar syrup and molasses from beet processing containing 620 and 570 mg/mL
      sucrose, respectively, were assayed as low-cost and available substrates for the
      enzymatic synthesis of fructo-oligosaccharides (FOSs). A commercial pectinase
      (Pectinex Ultra SP-L, from Aspergillus aculeatus) characterized by the presence
      of a transfructosylating activity was used as a biocatalyst. The FOS production
      increased when lowering the initial pH value of syrup (7.5) and molasses (8.9) to
      5.5. Sugar syrup and molasses were diluted in order to reduce substrate
      viscosity; interestingly, the percentage of FOS with regards to total sugars
      remained almost constant, which indicated a high transferase-to-hydrolase ratio
      for this enzyme. Kinetics of FOS production was analyzed. Using approximately 10
      U transfructosylating activity per g sucrose, the FOS concentration reached a
      maximum of 388 mg/mL after 30 h using syrup and 235 mg/mL in 65 h with molasses.
      These values corresponded to approximately 56 and 49% (w/w), respectively, of the
      total amount of carbohydrates in the mixture. The enzyme was also covalently
      immobilized on an epoxy-activated polymethacrylate-based polymer (Sepabeads EC
      EP5). We found that immobilized Pectinex Ultra SP-L can be efficiently applied to
      the synthesis of FOS using syrup and molasses as substrates.

PMID- 16608217
TI  - Solvent-free lipase-catalyzed preparation of long-chain alkyl phenylpropanoates
      and phenylpropyl alkanoates.
AB  - An enzymatic method was developed for the preparation of medium- or long-chain
      alkyl 3-phenylpropenoates (alkyl cinnamates), particularly alkyl hydroxy- and
      methoxy-substituted cinnamates such as oleyl p-coumarate and oleyl ferulate. The
      various alkyl cinnamates were formed in high to moderate yield by lipase
      catalyzed esterification of cinnamic acid and its analogues with fatty alcohols
      in vacuo at moderate temperatures in the absence of drying agents and solvents.
      Immobilized Candida antarctica lipase B was the most effective biocatalyst for
      the various esterification reactions. The relative esterification activities were
      of the following order: dihydrocinnamic > cinnamic > 3-methoxycinnamic >
      dihydrocaffeic approximately 3-hydroxycinnamic > 4-methoxycinnamic > 2
      methoxycinnamic > 4-hydroxycinnamic > ferulic approximately 3,4-dimethoxycinnamic
      > 2-hydroxycinnamic acid. With respect to the position of the substituents at the
      phenyl moiety, the esterification activity increased in the order meta > para >
      ortho. Rhizomucor miehei lipase demonstrated moderate esterification activity.
      Compounds with inverse chemical structure, that is, 3-phenylpropyl alkanoates
      such as 3-(4-hydroxyphenyl)propyl oleate, were also obtained in high yield by
      esterification of fatty acids with the corresponding 3-phenylpropan-1-ols.

PMID- 16608218
TI  - Rhodamine-pink as a genetic marker for yeast populations in wine fermentation.
AB  - Winemaking with selected yeasts requires simple techniques to monitor the
      inoculated yeast. New high-concentration rhodamine-resistant mutants and low
      concentration rhodamine-pink mutants, easy to detect by replica-plate assay, were
      obtained from selected wine yeasts. The rhodamine-pink mutations were dominant
      and were located at the pdr5 locus that encodes for the Pdr5 ATP-binding cassette
      multidrug resistance transporter. The mutants were genetically stable but had
      lost the killer phenotype of the parent yeast strain. They were genetically
      improved by elimination of recessive growth-retarding alleles followed by
      crossing with selected killer wine yeasts. Several spore-clones were selected
      according to their must fermentation kinetics and the organoleptic quality of the
      wine. Some spore-clones were tested in industrial winemaking, and they were
      easily monitored during must fermentation using a simple color-plate assay. They
      accounted for >96% of the total yeasts in the must, and the resulting wine had as
      good a quality as those made with standard commercial wine yeasts. The rhodamine
      pink yeasts may also be detected by direct seeding onto rhodamine agar or by
      observation under fluorescence microscopy. These possibilities greatly reduce the
      time of analysis and make the monitoring procedure for rhodamine-pink yeasts
      faster, easier, and cheaper than for the genetically marked wine yeasts obtained
      previously.

PMID- 16608219
TI  - Phytoremediation of the herbicides atrazine and metolachlor by transgenic rice
      plants expressing human CYP1A1, CYP2B6, and CYP2C19.
AB  - This study evaluated the expression of human cytochrome P450 genes CYP1A1,
      CYP2B6, and CYP2C19 in rice plants (Oryza sativa cv. Nipponbare) introduced using
      the plasmid pIKBACH. The transgenic rice plants (pIKBACH rice plants) became more
      tolerant toward various herbicides than nontransgenic Nipponbare rice plants.
      Rice plants expressing pIKBACH grown in soil showed tolerance to the herbicides
      atrazine, metolachlor, and norflurazon and to a mixture of the three herbicides.
      The degradation of atrazine and metolachlor by pIKBACH rice plants was evaluated
      to confirm the metabolic activity of the introduced P450s. Although both pIKBACH
      and nontransgenic Nipponbare rice plants could decrease the amounts of the
      herbicides in plant tissue and culture medium, pIKBACH rice plants removed
      greater amounts in greenhouse experiments. The ability of pIKBACH rice plants to
      remove atrazine and metolachlor from soil was confirmed in large-scale
      experiments. The metabolism of herbicides by pIKBACH rice plants was enhanced by
      the introduced P450 species. Assuming that public and commercial acceptance is
      forthcoming, pIKBACH rice plants may become useful tools for the breeding of
      herbicide-tolerant crops and for phytoremediation of environmental pollution by
      organic chemicals.

PMID- 16608220
TI  - Effect of combined heat and high-pressure treatments on the texture of chicken
      breast muscle (pectoralis fundus).
AB  - Commercially supplied chicken breast muscle was subjected to simultaneous heat
      and pressure treatments. Treatment conditions ranged from ambient temperature to
      70 degrees C and from 0.1 to 800 MPa, respectively, in various combinations.
      Texture profile analysis (TPA) of the treated samples was performed to determine
      changes in muscle hardness. At treatment temperatures up to and including 50
      degrees C, heat and pressure acted synergistically to increase muscle hardness.
      However, at 60 and 70 degrees C, hardness decreased following treatments in
      excess of 200 MPa. TPA was performed on extracted myofibrillar protein gels that
      after treatment under similar conditions revealed similar effects of heat and
      pressure. Differential scanning calorimetry analysis of whole muscle samples
      revealed that at ambient pressure the unfolding of myosin was completed at 60
      degrees C, unlike actin, which completely denatured only above 70 degrees C. With
      simultaneous pressure treatment at >200 MPa, myosin and actin unfolded at 20
      degrees C. Unfolding of myosin and actin could be induced in extracted
      myofibrillar protein with simultaneous treatment at 200 MPa and 40 degrees C.
      Electrophoretic analysis indicated high pressure/temperature regimens induced
      disulfide bonding between myosin chains.

PMID- 16608221
TI  - Modifications of trout (Oncorhynchus mykiss) muscle proteins by preslaughter
      activity.
AB  - The effect of two different preslaughter procedures (limited or 15-min intense
      muscular activity) on muscle trout proteins was investigated. Muscle was sampled
      45 min and 24 h post-mortem, proteins were separated using two-dimensional
      electrophoresis, and spots of interest were tentatively identified by MALDI-TOF
      spectrometry. Twenty-nine and 4 spots were differentially represented between the
      two groups of fish at 45 min and 24 h post-mortem, respectively. Spots that could
      be identified corresponded mainly to proteins involved in energy-producing
      pathways (triosephosphate isomerase, enolase, pyruvate dehydrogenase) or to
      structural proteins (desmin, cap-Z, myosin heavy chain fragment). Persistent
      under-representation of desmin, a key cytoskeletal protein, in fish submitted to
      intense muscular activity suggests that such a preslaughter treatment can have an
      effect on post-mortem muscle integrity.

PMID- 16608222
TI  - Effect of storage on secoiridoid and tocopherol contents and antioxidant activity
      of monovarietal extra virgin olive oils.
AB  - The degradation of secoiridoid, tocopherol, and antioxidant activity in extra
      virgin olive oils (EVOOs) was studied during 8 months of storage in closed
      bottles in the dark, at 40 and 25 degrees C. Picual, Arbequina, Taggiasca, and
      Colombaia monovarietal EVOOs possessing quite different fatty acid and
      antioxidant contents were used. The secoiridoid aglycones, namely, the oleuropein
      and ligstroside derivatives, and alpha-tocopherol decreased following pseudo
      first-order kinetics. In all EVOOs oleuropein derivatives were less stable than
      the corresponding ligstroside derivatives and alpha-tocopherol. Accordingly,
      overall antioxidant activity decreased following pseudo-first-order kinetics,
      with rate constants ranging from 0.85 x 10(-)(3) to 4.1 x 10(-)(3) days(-)(1) at
      40 degrees C and from 0.8 x 10(-)(3) to 1.5 x 10(-)(3) days(-)(1) at 25 degrees
      C. According to both the antioxidant activity and the hydrolysis and oxidation
      indices established by EU regulation to assess EVOO quality, Colombaia oil was
      the least stable, followed by Taggiasca, Arbequina, and Picual oils. Despite
      antioxidant degradation, EVOOs with high antioxidant contents were still
      "excellent" after 240 days of storage at 40 degrees C. These data led to the
      conclusion that the beneficial properties of EVOOs due to antioxidant activity
      can be maintained throughout their commercial lives.

PMID- 16608223
TI  - Oxalate content of cereals and cereal products.
AB  - Detailed knowledge of food oxalate content is of essential importance for dietary
      treatment of recurrent calcium oxalate urolithiasis. Dietary oxalate can
      contribute considerably to the amount of urinary oxalate excretion. Because
      cereal foods play an important role in daily nutrition, the soluble and total
      oxalate contents of various types of cereal grains, milling products, bread,
      pastries, and pasta were analyzed using an HPLC-enzyme-reactor method. A high
      total oxalate content (>50 mg/100 g) was found in whole grain wheat species
      Triticum durum (76.6 mg/100 g), Triticum sativum (71.2 mg/100 g), and Triticum
      aestivum (53.3 mg/100 g). Total oxalate content was comparably high in whole
      grain products of T. aestivum, that is, wheat flakes and flour, as well as in
      whole grain products of T. durum, that is, couscous, bulgur, and pasta. The
      highest oxalate content was demonstrated for wheat bran (457.4 mg/100 g). The
      higher oxalate content in whole grain than in refined grain cereals suggests that
      oxalic acid is primarily located in the outer layers of cereal grains. Cereals
      and cereal products contribute to the daily oxalate intake to a considerable
      extent. Vegetarian diets may contain high amounts of oxalate when whole grain
      wheat and wheat products are ingested. Recommendations for prevention of
      recurrence of calcium oxalate stone disease have to take into account the oxalate
      content of these foodstuffs.

PMID- 16608224
TI  - Alkylresorcinol content and homologue composition in durum wheat (Triticum durum)
      kernels and pasta products.
AB  - The total alkylresorcinol (AR) content and relative homologue composition of 21
      durum wheat (Triticum durum) kernel samples, as well as 5 pasta products and the
      corresponding flour mixtures, were determined. Durum wheat contained on average
      455 microg/g ARs, and the average relative homologue composition was C17:0
      (0.4%), C19:0 (14%), C21:0 (58%), C23:0 (21%), and C25:0 (6.5%). The homologue
      composition was found to be relatively consistent among samples, with durum wheat
      being different from common wheat by having a higher proportion of the longer
      homologues. No differences in content or homologue composition were observed in
      pasta products compared to flour ingredients, showing that alkylresorcinols are
      stable during pasta processing. The ratio of the homologues C17:0 to C21:0 was <
      or =0.02 for whole grain durum wheat products, which is different from those of
      common wheat (0.1) and rye (0.9).

PMID- 16608225
TI  - Essential and toxic elements in seafood available in poland from different
      geographical regions.
AB  - The concentrations of 15 elements (Cu, Fe, Mn, Zn, Co, Ni, Cr, Se, Cd, Pb, Hg,
      Ca, Na, K, and Mg) were determined in the edible parts of shellfish on sale in
      the local market in Gdansk. The samples consisted of three groups--crustaceans,
      molluscs, and surimi--that are processed to different degrees. For the purposes
      of this analysis, they were dried, homogenized, and digested in an automatic
      microwave system. The samples were analyzed quantitatively for Cu, Zn, Fe, Mn,
      Co, Ni, Cr, Mg, Na, K, and Ca (F-AAS), Cd and Pb (GF-AAS), Se (HG-AAS), and Hg
      (CV-AAS). The elemental levels detected in shellfish were compared to those in
      cod, herring, pork, beef, chicken, and eggs. The recommended dietary allowance
      (RDA) of essential elements and the provisional tolerable weekly intake (PTWI) of
      toxic elements were estimated. With factor analysis of the data, taxonomically
      different groups of raw and processed shellfish could be distinguished.

PMID- 16608226
TI  - Mechanisms of cuticular uptake of xenobiotics into living plants: evaluation of a
      logistic-kinetic penetration model.
AB  - The objective of this study was to determine whether a logistic-kinetic
      penetration model could be applied to whole plant uptake. Uptake over 24 h was
      determined for three model compounds, applied in the presence and absence of
      surfactants, into the leaves of two plant species. Data for two time intervals
      were used in the model to predict uptake at intermediate intervals and compared
      with experimental results. Overall, the model fit the whole plant uptake data
      well. The study confirmed that an increase (or decrease) in active ingredient
      (ai) concentration or an increase in contact area will have no effect on the
      penetration rate factor, q, within the normal working concentration range. This
      enabled uptake to be predicted at different times for concentrations of ai not
      already studied, having first derived q for one concentration of the formulation
      of interest and having 24 h (maximum) uptake results for all formulations and
      concentrations of interest. The advantages of the models and equations described
      are that few variables are required, and they are simple to measure.

PMID- 16608227
TI  - Preferential sorption of phenolic phytotoxins to soil: implications for altering
      the availability of allelochemicals.
AB  - Allelopathy, secondary metabolite-mediated plant-to-plant interaction, is gaining
      application in current agricultural science as well as in invasion ecology.
      However, the role of sorption to soil in modifying the bioavailability of
      components in complex allelochemical mixtures is still obscure. Hence, the role
      of preferential sorption to soil in altering the chemical composition of plant
      exudates was studied in a silt loam soil using representative mixtures of plant
      phenolic acids, namely, hydroxybenzoic acid, vanillic acid, coumaric acid, and
      ferulic acid. The experiment was conducted using a batch equilibration technique,
      and data were fitted to a Freundlich isotherm. The concentration-dependent
      sorption coefficient (K(d)) at 10 microg mL(-)(1) was used to assess the sorption
      affinity of phenolic acids across different systems. Along with solid phase
      dissolution, all of the phenolic acids exhibited strong site-specific sorption,
      as evident from their nonlinear isotherms. Removal of organic matter
      substantially decreased the sorption affinity of all phenolic acids. Direct
      competition for sorption sites was observed even at low concentrations of
      phenolic acids. The K(d) of hydroxybenzoic acid was decreased more than 90% in
      the presence of coumaric acid. About 95% of sorbed vanillic acid was displaced
      into the soil solution in the presence of ferulic acid. Hydroxybenzoic acid did
      not affect the sorption affinity of other phenolic acids significantly, whereas
      ferulic acid showed low displacement by other phenolic acids. The displacement
      pattern indicated directional sorption of phenolic acids with -OH and -COOH
      groups. Soil organic matter was associated with preferential sorption. This is
      the first study to elucidate competitive sorption characteristics of plant
      secondary metabolites in soil matrix. The results demonstrate that preferential
      sorption to soil can alter the availability of plant exudates in mixtures and
      thus may mediate their phytotoxic effects.

PMID- 16608228
TI  - Isolation and antifungal and antioomycete activities of staurosporine from
      Streptomyces roseoflavus strain LS-A24.
AB  - The actinomycete strain LS-A24 active against some plant fungal and oomycete
      pathogens was isolated from a soil sample of the Sunghwan Lake in Korea. The cell
      wall composition and spore shape of strain LS-A24 were LL-diaminopimelic acid and
      spiral type, respectively. On the basis of the physiological and biochemical
      characteristics and 16S ribosomal DNA sequence analysis, strain LS-A24 was
      identical to Streptomyces roseoflavus. An antifungal and antioomycete antibiotic
      was isolated from LS-A24 using various chromatographic procedures. The molecular
      formular of the antibiotic was determined to be C(28)H(26)N(4)O(3), and on the
      basis of the NMR data, the antibiotic was confirmed to be staurosporine,
      2,3,10,11,12,13-hexahydro-10R-methoxy-9S-methyl-11R-methylamino-9S,13R-epoxy
      1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-1-one.
      Staurosporine completely inhibited the mycelial growth of Colletotrichum
      orbiculare, Phytophthora capsici, Rhizoctonia solani, Botrytis cinerea, and
      Cladosporium cucumerinum with minimum inhibitory concentration (MIC) values of 1
      50 microg/mL for MICs. Staurosporine also was active against Saccharomyces
      cerevisiae, Bacillus subtilis ssp. subtilis, and Xanthomonas vesicatoria.
      Staurosporine and the commercial fungicide metalaxyl inhibited the development of
      Phytophthora blight on pepper plants. However, the control efficacy of
      staurosporine against the Phytophthora disease was somewhat less than that of
      metalaxyl. This is the first study to isolate staurosporine from S. roseoflavus
      and demonstrate its in vitro and in vivo antioomycete activity against P.
      capsici.

PMID- 16608229
TI  - Physicochemical model to interpret the kinetics of aroma extraction during wine
      aging in wood. Model limitations suggest the necessary existence of biochemical
      processes.
AB  - A model based on physicochemical parameters has been developed and applied to the
      study of the kinetics of extraction of aroma compounds from oak casks having been
      used a variable number of times. Two major deviations from the model can be
      observed: a strong seasonal dependence of extraction (unexpected in a
      thermostated cellar); and higher yields with a smaller number of longer
      extractions. 4-Propylguaiacol follows both behaviors, and its levels have been
      found to be closely related to those of 4-ethylguaiacol and to the number of uses
      of the barrel, which suggests that this compound may be formed by the same
      microorganisms forming ethylphenols from a precursor found in wood. Although the
      extraction kinetics of all aroma compounds appear to be more or less mediated by
      the action of microorganisms, those of whiskeylactones, eugenol, and 4-allyl-2,6
      dimethoxyphenol are more in accordance with the physicochemical model, whereas
      those of vanillin, syringaldehyde, furfuryl alcohol, and, of course, 4
      propylguaiacol are much more coherent with a microbiological
      extraction/formation.

PMID- 16608230
TI  - Potent inhibitory effects of black tea theaflavins on off-odor formation from
      citral.
AB  - The present study was conducted to investigate the ability of black tea
      theaflavins to inhibit the off-odor formation from citral under acidic aqueous
      conditions. Acidic buffer solutions (pH 3.0) containing citral (10 mg/L) and an
      inhibitor (0-5 mg/L) were stored at 40 degrees C for 2 weeks. The formation of
      possible off-odorants p-cresol and p-methylacetophenone in the citral solutions
      was monitored by high-performance liquid chromatography. A mixture of the
      theaflavins showed inhibitory effects on the formation of both p-cresol and p
      methylacetophenone with 50% inhibitory concentrations (IC(50)) of 0.18 and 0.10
      mg/L, respectively. Individual theaflavins and a structurally related compound,
      purpurogallin, also inhibited the formation of both off-odorants, with the lowest
      IC(50) values for theaflavin 3,3'-digallate (0.17 and 0.06 mg/L for p-cresol and
      p-methylacetophenone, respectively). On the other hand, a mixture of green tea
      catechins and its major constituent, (-)-epigallocatechin gallate, showed
      relatively high IC(50) values for the formation of p-methylacetophenone (1.29 and
      1.28 mg/L, respectively) and showed no inhibitory effect on the formation of p
      cresol. The results of the sensory evaluation showed that the off-odor intensity
      of the stored citral solution was significantly decreased by the addition of the
      theaflavin mixture at concentrations of 0.5 mg/L and above. In addition, the
      calculation of the odor activity values (OAVs) for the volatile compounds
      detected by a gas chromatographic analysis indicated that the total OAVs of the
      major volatile compounds in the citral solution were significantly decreased by
      the addition of the theaflavins.

PMID- 16608231
TI  - Influence of the species and geographical location on volatile composition of
      Spanish oak wood (Quercus petraea Liebl. and Quercus robur L.).
AB  - The influence of the species and geographical origin on the volatile composition
      of wood samples from 80 Spanish oaks (55 Quercus petraea Liebl. and 25 Quercus
      robur L.) has been studied. Oak volatile components were isolated by simultaneous
      distillation-extraction and analyzed by gas chromatography-mass spectrometry. cis
      and trans-beta-methyl-gamma-octalactones were the main constituents, the cis
      stereoisomer being predominant. Other important volatile components were
      furfural, 5-methylfurfural, guaiacol, eugenol, vanillin, or syringaldehyde. The
      main differences were established between species, Quercus petraea being
      significantly richer in volatile compounds than Quercus robur; however, the
      variability found among trees was high. Differences among geographical
      provenances were much less important than those found between species.

PMID- 16608232
TI  - Comparison of volatile constituents of Persicaria odorata(Lour.) Sojak (Polygonum
      odoratum Lour.) and Persicaria hydropiper L. Spach (Polygonum hydropiper L.).
AB  - Polygonum odoratum Lour. has been reclassified as Persicaria odorata (Lour.)
      Sojak [Wilson, K. L. Polygonum sensu lato (Polygonaceae) in Australia. Telopea
      1988, 3, 177-182]; other synonyms currently used are Vietnamese mint or
      Vietnamese coriander and, in Malaysia, Daun Laksa or Laksa plant. The aerial
      parts of Laksa plant are highly aromatic, and they contain many organic compounds
      such as (Z)-3-hexenal, (Z)-3-hexenol, decanal, undecanal, and dodecanal that are
      typical for green, citrus, orange peel, and coriander odors. In addition to these
      aldehydes, 3-sulfanyl-hexanal and 3-sulfanyl-hexan-1-ol were discovered for the
      first time in this herb. The fresh leaves are pungent when they are chewed,
      although the active compound has never been identified. The pungency of
      Persicaria hydropiper (L.) Spach (formerly Polygonum hydropiper L., synonym water
      pepper) is produced by polygodial, a 1,4-dialdehyde derived from drimane
      terpenoids. We also identified polygodial as the active pungent compound in P.
      odorata (Lour.) Sojak.

PMID- 16608233
TI  - Use of an electrochemically etched platinum microelectrode for ascorbic acid
      mapping in oranges.
AB  - A positionable platinum microelectrode fabricated by electrochemical etching was
      used to monitor the concentration of ascorbic acid in fruits and vegetables.
      Studies carried out with ascorbate oxidase confirmed the suitability of the
      amperometric sensor to measure selectively the ascorbic acid content. The results
      obtained with the proposed method for ascorbic acid determination in orange
      juices compared well with those found by iodimetry with coulometrically generated
      iodine. The standard deviation calculated by measuring limiting current values in
      voltammograms was found to be 3% (n = 150). The sensor allowed the evaluation of
      the spatial distribution of ascorbic acid concentration in oranges by in-situ
      measurements. Ascorbic acid concentration maps show that in a perpendicular cut
      the concentration is higher near the peel to the center of the fruit. In a
      parallel cut, the concentration increases with the distance to the stem. A
      correlation between the ripening stage and the ascorbic acid concentration was
      also observed from electrochemical measurements, the content being higher in
      mature fruits.

PMID- 16608234
TI  - Gas and liquid phase acidity of natural antioxidants.
AB  - The gas phase and in solution absolute and relative acidities of nine natural
      systems contained in red and white wines were determined through theoretical
      B3LYP/6-311++G** calculations. The aim was to correlate these thermodynamic
      quantities to the ability that some of these compounds show in chelating metals
      ions to carry out an antioxidant action following a mechanism recently reported
      in the literature. Results indicated that both absolute and relative values are
      affected by molecular features such as electronic delocalization and conjugation
      and intramolecular hydrogen bonds. Polyphenols characterized by the ortho
      dihydroxy functionality were found to be good candidates to act as metal cation
      chelating ligands. Some differences in absolute acidities values were encountered
      in going from vacuum to water solution.

PMID- 16608235
TI  - Polar interactions in flavan-3-ol adsorption on solid surfaces.
AB  - The adsorption of flavan-3-ol monomers and grape seed procyanidin fractions of
      different mean degrees of polymerization was studied on three surfaces by means
      of adsorption isotherms. Reversibility upon dilution was also investigated. These
      surfaces were three polymeric microfiltration membranes, presenting close
      Lifshitz-van der Waals components of their surface tension but differing in their
      surface polar properties. The electron-donor character of the surface was of
      primary importance for the adsorption of nongalloylated monomers. Increasing the
      number of phenolic rings above two (galloylated monomers and procyanidins)
      sharply enhanced flavan-3-ol affinity for surfaces whatever their polarity.
      However, maximum adsorbed amounts were always much higher on the most polar
      material. The general trend was a partial reversibility with monomers, whereas an
      irreversible process was evidenced from the lowest molecular weight tannin
      fractions. This indicated the formation of multiple bonds with surfaces, in
      accordance with the high affinity type isotherms. The whole results indicated
      very different mechanisms in the buildup of the adsorbed layers when the surface
      electron-donor character varied.

PMID- 16608236
TI  - Use of the 1H nuclear magnetic resonance spectra signals from polyphenols and
      acids for chemometric characterization of cider apple juices.
AB  - The low field region (5.8-9.0 ppm) corresponding to aromatic protons and the
      region 1.8-3.0 ppm of the (1)H NMR spectra were used for characterization and
      chemometric differentiation of 52 apple juices obtained from six cider apple
      varieties. The data set consisted of 14 integrated areas corresponding to
      resonances from acids and phenolic compounds. Multivariate procedures based on
      hierarchical cluster and discriminant analysis were performed on selected signals
      of the spectra to determine whether it was possible to distinguish the different
      juices. Cluster analysis was able to satisfactorily classify the six apple
      varieties. Discriminant analysis, by means of stepwise procedure for variables
      selection and leave-one-out for cross-validation, was applied to 40 samples from
      the year 2001, obtaining recognition and prediction abilities of 100%. The most
      discriminant variables corresponded to poliphenols, (-)-epicatechin, phloridzin
      phloretin, and p-coumaric, chlorogenic, and malic acids. The classification model
      was applied to 12 samples from apples harvested in the years 2002 and 2003, and
      the prediction ability was 91.7%.

PMID- 16608237
TI  - Molecular cloning and functional identification of invertase isozymes from green
      bamboo Bambusa oldhamii.
AB  - Three Bo beta fruct cDNAs encoding acid invertases were cloned from shoots of the
      green bamboo Bambusa oldhamii. On the basis of the amino acid sequences of their
      products and phylogenetic analyses, Bo beta fruct1 and Bo beta fruct2 were
      determined to encode cell wall invertases, whereas Bo beta fruct3encodes a
      vacuolar invertase. The recombinant proteins encoded by Bo beta fruct2 and Bo
      beta fruct3 were produced in Pichia pastoris and purified to near homogeneity
      using ammonium sulfate fractionation and immobilized metal affinity
      chromatography. The pH optima, pI values, and substrate specificities of the
      isolated enzymes were consistent with those of plant cell wall or vacuolar
      invertases. The growth-dependent expression of Bo beta fruct1 and Bo beta fruct2
      in the base regions of shoots underscores their roles in sucrose unloading and
      providing substrates for shoot growth. Its high sucrose affinity suggests that
      the Bo beta fruct2-encoded enzyme is important for maintaining the sucrose
      gradient between source and sink organs, while the predominant expression of Bo
      beta fruct3 in regions of active cell differentiation and expansion suggests
      functions in osmoregulation and cell enlargement.

PMID- 16608238
TI  - Stability of barley and malt lipid transfer protein 1 (LTP1) toward heating and
      reducing agents: relationships with the brewing process.
AB  - Barley lipid transfer protein (LTP1) is a heat-stable and protease-resistant
      albumin that concentrates in beer, where it participates in the formation and
      stability of beer foam. Whereas the barley LTP1 does not display any foaming
      properties, the corresponding beer protein is surface-active. Such an improvement
      is related to glycation by Maillard reactions on malting, acylation on mashing,
      and structural unfolding on brewing. The structural stability of purified barley
      and glycated malt LTP1 toward heating has been analyzed. Whatever the
      modification, lipid adduction or glycation, barley LTP1s are highly stable
      proteins that resisted temperatures up to 100 degrees C. Unfolding of LTP1
      occurred only when heating was conducted in the presence of a reducing agent. In
      the presence of sodium sulfite, the lipid-adducted barley and malt LTP1 displayed
      higher heat stability than the nonadducted protein. Glycation had no or weak
      effect on heat-induced unfolding. Finally, it was shown that unfolding occurred
      on wort boiling before fermentation and that the reducing conditions are provided
      by malt extract.

PMID- 16608239
TI  - Characterization of storage proteins in wild (Glycine soja) and cultivated
      (Glycine max) soybean seeds using proteomic analysis.
AB  - A combined proteomic approach was applied for the separation, identification, and
      comparison of two major storage proteins, beta-conglycinin and glycinin, in wild
      (Glycine soja) and cultivated (Glycine max) soybean seeds. Two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE) with three different immobilized pH
      gradient (IPG) strips was an effective method to separate a large number of
      abundant and less-abundant storage proteins. Most of the subunits of beta
      conglycinin were well-separated in the pH range 3.0-10.0, while acidic and basic
      glycinin polypeptides were well-separated in pH ranges 4.0-7.0 and 6.0-11.0,
      respectively. Although the overall distribution pattern of the protein spots was
      similar in both genotypes using pH 3.0-10.0, variations in number and intensity
      of protein spots were better resolved using a combination of pH 4.0-7.0 and pH
      6.0-11.0. The total number of storage protein spots detected in wild and
      cultivated genotypes was approximately 44 and 34, respectively. This is the first
      study reporting the comparison of protein profiles of wild and cultivated
      genotypes of soybean seeds using proteomic tools.

PMID- 16608240
TI  - Antioxidant effect of two virgin olive oils depends on the concentration and
      composition of minor polar compounds.
AB  - In vitro studies show that some individual minor polar phenolic compounds (MPC)
      present in virgin olive oil prevent oxidation of human low-density lipoproteins
      (LDL), but few data are available on the antioxidant effect of whole oil extract.
      Thus, whole virgin olive extracts were studied to determine whether they maintain
      the antioxidant activity and whether this last is linked to MPC composition of a
      single virgin oil. Using HPLC-DAD the MPC content in Taggiasca and Seggianese
      virgin olive oils was measured. Taggiasca oil was less rich in total MPC (208.5
      mg/L) than Seggianese oil (441.9 mg/L). In addition, the major compounds of
      Taggiasca oil were lignan derivatives, whereas the major compounds in Seggianese
      oils were secoiridoid derivatives. Moreover, Taggiasca oil was practically free
      of 5-hydroxytyrosol and 5-hydroxytyrosol derivatives, deacetoxy-oleuropein
      aglycone and oleuropein aglycone. The antioxidant activity of the oils on human
      LDL was evaluated by measuring malondialdehyde and conjugate diene generation
      induced by copper ions. In both tests, the oil extracts dose-dependently reduced
      malondialdehyde and conjugate diene generation. Moreover, antioxidant potency
      correlated with total MPC; thus, Seggianese extract was more active. The two oils
      differed quantitatively and qualitatively, and these differences influenced their
      biological activities; thus clinical trials focused on studying the effects of
      olive oils should specify the oils used.

PMID- 16608241
TI  - Neuroprotective effects of resveratrol on cerebral ischemia-induced neuron loss
      mediated by free radical scavenging and cerebral blood flow elevation.
AB  - Resveratrol is a natural phytoestrogen and possesses many biological functions
      such as anti-inflammatory activity and protection against atherosclerosis and
      myocardial infraction. The present study was carried out to elucidate the
      neuroprotective effect and possible mechanism of resveratrol on cerebral ischemia
      induced hippocampus neuron loss. Sixty adult male rats underwent general
      anesthesia (urethane, 1.4 g/kg, i.p.) and were divided into three groups: sham
      operation, ischemia treatment, and ischemia combined with resveratrol
      administration (20 mg/kg, i.v.). The carotid artery was bilaterally ligated to
      induce cerebral ischemia. Microdialysis and high-performance liquid
      chromatography were used to analyze dihydroxybenzoic acid (DHBA) that reflected
      the hippocampal hydroxyl radical level. Hippocampal nitric oxide was assayed
      among different groups. During cerebral ischemia, the hydroxyl radical levels
      were elevated in rats and animals displayed severe neuronal loss. A single dose
      of resveratrol significantly increased the nitric oxide level and decreased the
      hydroxyl radical level. The reduction of cerebral blood flow and neuronal loss
      were also attenuated by resveratrol treatment. The results demonstrated that a
      single infusion of resveratrol could elicit neuroprotective effects on cerebral
      ischemia-induced neuron damage through free radical scavenging and cerebral blood
      elevation due to NO release.

PMID- 16608242
TI  - Comparison of protective effects between cultured Cordyceps militaris and natural
      Cordyceps sinensis against oxidative damage.
AB  - The Chinese herb DongChong-XiaCao originating from Cordyceps sinensis is widely
      used as a traditional medicine in China for treatment of a wide variety of
      diseases. The extracts of Cordyceps sinensis (CSE) and Cordyceps militaris (CME)
      are well-known for their biological effects. In the present study, the
      antioxidant efficiency of CME and CSE in protecting lipid, protein, and low
      density lipoprotein (LDL) against oxidative damage was investigated. CME and CSE
      showed weakly inhibitory effect on liposome oxidation, that of CME being superior
      to that of CSE. As for the protein oxidation model system, the inhibitory effect
      of CME on protein oxidation was inferior to that of CSE. CME and CSE at 1.0 mg/mL
      showed 50.5 and 67.1% inhibition of LDL oxidation, respectively. The contents of
      bioactive ingredients cordycepin and adenosine in CME are higher than those of
      CSE; however, both cordycepin and adenosine showed no significant antioxidant
      activity as determined by the Trolox equivalent antioxidant capacity method.
      Polyphenolic and flavonoid contents are 60.2 and 0.598 microg/mL in CME and 31.8
      and 0.616 microg/mL in CSE, respectively, which may in part be responsible for
      their antioxidant activities. In addition, a polysaccharide present in CME and
      CSE displayed antioxidant activity, which suggested that the activity might be
      derived partly from polysaccharides of CME and CSE. The tendency to scavenge the
      ABTS(*)(+) free radical and the reducing ability of CME and CSE display
      concentration-dependent manners, suggesting that CME and CSE may be potent
      hydrogen donators. On the basis of the results obtained, the protective effects
      of CME and CSE against oxidative damage of biomolecules are a result of their
      free radical scavenging abilities.

PMID- 16608243
TI  - Characterization of the essential oil volatiles of Satureja thymbra and Satureja
      parnassica: influence of harvesting time and antimicrobial activity.
AB  - Seasonal variation in chemical composition of essential oils obtained from
      Satureja parnassica subsp. parnassica Heldr. & Sart ex Boiss. and Satureja
      thymbra L. was determined by GC and GC-MS analysis. The in vitro antibacterial
      activities of these essential oils were evaluated at two different initial levels
      against two common foodborne bacteria. Their minimum inhibitory concentration
      (MIC) and noninhibitory concentration (NIC) values were determined via an
      innovative automated technique, which was applied on a Malthus apparatus
      combining the conductance measurements with the common dilution method. The
      essential oil concentration fluctuated greatly during the period examined and
      established that the Satureja oils obtained during the flowering period were the
      most potent, exhibiting the lowest MIC values and retaining remarkable
      bactericidal properties. Thus, they represent an inexpensive source of natural
      antibacterial substances that exhibit potential for use in food systems to
      prevent the growth of foodborne bacteria and to extend the shelf life of the
      processed food.

PMID- 16608244
TI  - Characterization of volatile constituents of Haplopappus greenei and studies on
      the antifungal activity against phytopathogens.
AB  - Essential oil of Haplopappus greenei A. Gray was obtained by hydrodistillation of
      aerial parts, which were subsequently analyzed by gas chromatography and gas
      chromatography-mass spectrometry. Major components were identified as carvacrol
      (8.7%), beta-pinene (7.6%), trans-pinocarveol (6.2%), and caryophyllene oxide
      (5.8%), respectively. In total, 104 components representing 84.9% of the
      investigated essential oil were characterized. Furthermore, the essential oil was
      evaluated for antimalarial, antimicrobial, and antifungal activities. However,
      only antifungal activity was observed against the strawberry anthracnose-causing
      fungal plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and
      Colletotrichum gloeosporioides using the direct overlay bioautography assay.
      Major essential oil components were also evaluated for antifungal activity; the
      carvacrol standard demonstrated nonselective activity against the three
      Colletotrichum species and the other compounds were inactive.

PMID- 16608245
TI  - Lipoxygenase from banana leaf: purification and characterization of an enzyme
      that catalyzes linoleic acid oxygenation at the 9-position.
AB  - The objective of the present study was to purify and characterize the
      lipoxygenase (LOX) from banana leaf (Giant Cavendishii, AAA), an unutilized
      bioresource. LOX was extracted, isolated, and purified 327-fold using 25-50%
      saturation of ammonium sulfate fractionation, hydroxyapatite column separation,
      and gel filtration on Superdex 200. The molecular mass of the purified LOX was 85
      kDa, K(m) was 0.15 mM, and V(max) was 2.4 microM/min.mg using linoleic acid as
      substrate. Triton X-100 was required in the extraction medium; otherwise, no LOX
      activity was detected. LOX activity increased with the concentration of Triton X
      100 with an optimum at 0.1%. The optimal pH of the purified LOX from banana leaf
      was 6.2, and optimal temperature was 40 degrees C. The LOX showed the highest
      reactivity toward 18:2 followed by 18:3 and 20:4. A very low reaction rate was
      observed toward 20:5 and 22:6. On the basis of retention time in normal phase
      HPLC, the products of 18:2 or 18:3 catalyzed by purified LOX were
      hydroperoxyoctadecadienoic acid or hydroperoxyoctadecatrienoic acid. It seems
      that 9-LOX is the predominant enzyme in banana leaf. Banada leaf dried at 110
      degrees C for 2 h developed algal aroma. Banana leaf extract stored at 10 degrees
      C for 12 h formed an oolong tea-like flavor. Banana leaf extract reacted with
      18:2 or soybean oil pretreated with bacterial lipase produced green and melon
      like aroma, whereas the same reaction with 18:3 produced a sweet, fruity,
      cucumber-like flavor note.

PMID- 16608246
TI  - In vitro cytotoxicity of nonpolar constituents from different parts of kava plant
      (Piper methysticum).
AB  - Kava (Piper methysticum), a perennial shrub native to the South Pacific islands,
      has been used to relieve anxiety. Recently, several cases of severe
      hepatotoxicity have been reported from the consumption of dietary supplements
      containing kava. It is unclear whether the kava constituents, kavalactones, are
      responsible for the associated hepatotoxicity. To investigate the key components
      responsible for the liver toxicity, bioassay-guided fractionation was carried out
      in this study. Kava roots, leaves, and stem peelings were extracted with
      methanol, and the resulting residues were subjected to partition with a different
      polarity of solvents (hexane, ethyl acetate, n-butanol, and water) for evaluation
      of their cytotoxicity on HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase and aspartate
      aminotransferase enzyme leakage assays. Organic solvent fractions displayed a
      much stronger cytotoxicity than water fractions for all parts of kava. The hexane
      fraction of the root exhibited stronger cytotoxic effects than fractions of root
      extracted with other solvents or extracts from the other parts of kava. Further
      investigations using bioassay-directed isolation and analysis of the hexane
      fraction indicated that the compound responsible for the cytotoxicity was
      flavokavain B. The identity of the compound was confirmed by (1)H and (13) C NMR
      and MS techniques.

PMID- 16608247
TI  - Comparative analysis of the effects of locally used herbicides and their active
      ingredients on a wild-type wine Saccharomyces cerevisiae strain.
AB  - Herbicides are released to the environment with potential ecotoxicological risks
      for mammals. Yeast is a good model to elucidate toxicity mechanisms. We
      investigated how three commercial herbicides (Proper Energy, Pointer, and
      Silglif) and their active ingredients (respectively, fenoxaprop-P-ethyl,
      tribenuron methyl, and glyphosate) can affect biological activities of an
      oenological Saccharomyces cerevisiae strain, which may be resident on grape
      vineyards of the same geographical areas where herbicides are used. The use of
      commercial grade herbicides employed in Italy allowed us to reproduce the same
      conditions applied in crops; at the same time, assaying pure single active
      compounds made it possible to compare the effects obtained with commercial
      formulations. Interestingly, we found that while pure active compounds affect
      cell growth and metabolism at a lower extent, commercial preparations have a
      significant major negative influence on yeast biology.

PMID- 16608248
TI  - Zeptogram-scale nanomechanical mass sensing.
AB  - Very high frequency (VHF) nanoelectromechanical systems (NEMS) provide
      unprecedented sensitivity for inertial mass sensing. We demonstrate in situ
      measurements in real time with mass noise floor approximately 20 zg. Our best
      mass resolution corresponds to approximately 7 zg, equivalent to approximately 30
      xenon atoms or the mass of an individual 4 kDa molecule. Detailed analysis of the
      ultimate sensitivity of such devices based on these experimental results
      indicates that NEMS can ultimately provide inertial mass sensing of individual
      intact, electrically neutral macromolecules with single-Dalton (1 amu)
      resolution.

PMID- 16608249
TI  - Covalently linked Au nanoparticles to a viral vector: potential for combined
      photothermal and gene cancer therapy.
AB  - Hyperthermia can be produced by near-infrared laser irradiation of gold
      nanoparticles present in tumors and thus induce tumor cell killing via a
      bystander effect. To be clinically relevant, however, several problems still need
      to be resolved. In particular, selective delivery and physical targeting of gold
      nanoparticles to tumor cells are necessary to improve therapeutic selectivity.
      Considerable progress has been made with respect to retargeting adenoviral
      vectors for cancer gene therapy. We therefore hypothesized that covalent coupling
      of gold nanoparticles to retargeted adenoviral vectors would allow selective
      delivery of the nanoparticles to tumor cells, thus feasibilizing hyperthermia and
      gene therapy as a combinatorial therapeutic approach. For this, sulfo-N
      hydroxysuccinimide labeled gold nanoparticles were reacted to adenoviral vectors
      encoding a luciferase reporter gene driven by the cytomegalovirus promoter
      (AdCMVLuc). We herein demonstrate that covalent coupling could be achieved, while
      retaining virus infectivity and ability to retarget tumor-associated antigens.
      These results indicate the possibility of using adenoviral vectors as carriers
      for gold nanoparticles.

PMID- 16608250
TI  - Preparation of ultrathin self-standing polyelectrolyte multilayer membranes at
      physiological conditions using pH-responsive film segments as sacrificial layers.
AB  - A new system to obtain ultrathin self-standing polyelectrolyte multilayer
      membranes at physiological conditions is introduced. On the surface of a
      substrate, a hybrid film structure composed of two compartments, (1) a pH
      responsive film segment formed via hydrogen bonds and (2) a polyelectrolyte
      multilayer film on top of 1, was assembled. The pH-responsive polymer multilayer
      segments disintegrate at a neutral pH and release self-standing polyelectrolyte
      multilayer films. The obtained self-supporting polyelectrolyte multilayer
      membranes had thicknesses of 55 to several hundred nanometers and areas of a few
      square centimeters, approximately. The preparation method introduced here avoids
      harsh release conditions and thus broadens the choice of materials that can be
      incorporated into the self-standing film.

PMID- 16608251
TI  - Influence of nanowire density on the shape and optical properties of ternary
      InGaAs nanowires.
AB  - We have synthesized ternary InGaAs nanowires on (111)B GaAs surfaces by metal
      organic chemical vapor deposition. Au colloidal nanoparticles were employed to
      catalyze nanowire growth. We observed the strong influence of nanowire density on
      nanowire height, tapering, and base shape specific to the nanowires with high In
      composition. This dependency was attributed to the large difference of diffusion
      length on (111)B surfaces between In and Ga reaction species, with In being the
      more mobile species. Energy dispersive X-ray spectroscopy analysis together with
      high-resolution electron microscopy study of individual InGaAs nanowires shows
      large In/Ga compositional variation along the nanowire supporting the present
      diffusion model. Photoluminescence spectra exhibit a red shift with decreasing
      nanowire density due to the higher degree of In incorporation in more sparsely
      distributed InGaAs nanowires.

PMID- 16608252
TI  - Surface chemistry controls crystallinity of ZnS nanoparticles.
AB  - Combined small-angle and high energy wide-angle X-ray scattering measurements of
      nanoparticle size and structure permit interior strain and disorder to be
      observed directly in the real-space pair distribution function (PDF). PDF
      analysis showed that samples of ZnS nanoparticles with similar mean diameters
      (3.2-3.6 nm) but synthesized and treated with different low-temperature
      procedures possess a dramatic range of interior disorder. We used Fourier
      transform infrared spectroscopy to detect the surface species and the nature of
      surface chemical interactions. Our results suggest that there is a direct
      correlation between the strength of surface-ligand interactions and interior
      crystallinity.

PMID- 16608253
TI  - Nanoparticle-templated assembly of viral protein cages.
AB  - Self-assembly of regular protein surfaces around nanoparticle templates provides
      a new class of hybrid biomaterials with potential applications in medical imaging
      and in bioanalytical sensing. We report here the first example of efficiently
      self-assembled virus-like particles (VLPs) having a brome mosaic virus protein
      coat and a functionalized gold core. The present study indicates that
      functionalized gold particles can initiate VLP assembly by mimicking the
      electrostatic behavior of the nucleic acid component of the native virus. These
      VLP constructs are symmetric, with the protein stoichiometry and packaging
      properties indicating similarity to the icosahedral packing of the capsid.
      Moreover, a pH-induced swelling transition of the VLPs is observed, in direct
      analogy to the native virus.

PMID- 16608254
TI  - Structural and mechanical study of a self-assembling protein nanotube.
AB  - We report a structural characterization of self-assembling nanostructures. Using
      atomic force microscopy (AFM), we discovered that partially hydrolyzed alpha
      lactalbumin organizes in a 10-start helix forming tubes with diameters of only 21
      nm. We probed the mechanical strength of these nanotubes by locally indenting
      them with an AFM tip. To extract the material properties of the nanotubes, we
      modeled the experiment using finite element methods. Our study shows that
      artificial helical protein self-assembly can yield very stable, strong structures
      that can function either as a model system for artificial self-assembly or as a
      nanostructure with potential for practical applications.

PMID- 16608255
TI  - Measurement of the bending strength of vapor-liquid-solid grown silicon
      nanowires.
AB  - The fracture strength of silicon nanowires grown on a [111] silicon substrate by
      the vapor-liquid-solid process was measured. The nanowires, with diameters
      between 100 and 200 nm and a typical length of 2 microm, were subjected to
      bending tests using an atomic force microscopy setup inside a scanning electron
      microscope. The average strength calculated from the maximum nanowire deflection
      before fracture was around 12 GPa, which is 6% of the Young's modulus of silicon
      along the nanowire direction. This value is close to the theoretical fracture
      strength, which indicates that surface or volume defects, if present, play only a
      minor role in fracture initiation.

PMID- 16608256
TI  - Synchronous electrorotation of nanowires in fluid.
AB  - We demonstrate electrorotation of metal nanowires phase-locked to a driving
      alternating current electric field. Field rotation was accomplished by a low
      frequency signal that modulates the amplitude of the high-frequency field.
      Steady, synchronous rotation of the nanowires was observed for frequencies up to
      a maximum rotational frequency, which depends on the magnitude of the applied
      electric field. A locally two-dimensional nanowire fluid flow model was developed
      to calculate the viscous fluid drag torque, including drag contributions due to
      the proximity of the floor. Synchronicity and phase-lock angle predicted by
      equating the calculated fluid drag and electrical driving torques is in good
      agreement with experimentally determined values, which provides support for the
      model. Synchronous electrorotation allows for precise control of nanowire
      rotational speed and orientation for frequencies as low as a fraction of 1 Hz.
      Potential applications include reconfigurable polarization filters, microfluidic
      valves, and stirring devices.

PMID- 16608257
TI  - The mechanism of water diffusion in narrow carbon nanotubes.
AB  - Carbon nanotubes show exceptional physical properties that render them promising
      candidates as building blocks for nanostructured materials. Many ambitious
      applications, ranging from gene therapy to membrane separations, require the
      delivery of fluids, in particular aqueous solutions, through the interior of
      carbon nanotubes. To foster these and other applications, it is necessary to
      understand the thermodynamic and transport properties of water confined within
      long narrow carbon nanotubes. Previous theoretical work considered either short
      carbon nanotubes or short periods of time. By conducting molecular dynamics
      simulations in the microcanonical ensemble for water confined in infinitely long
      carbon nanotubes of diameter 1.08 nm, we show here that confined water molecules
      diffuse through a fast ballistic motion mechanism for up to 500 ps at room
      temperature. By comparing the results obtained for the diffusion of water to
      those obtained for the diffusion of a reference Lennard-Jones fluid, we prove
      here that long-lasting hydrogen bonds are responsible for the ballistic diffusion
      of water clusters in narrow carbon nanotubes, as opposed to spatial mismatches
      between pore-fluid and fluid-fluid attractive interactions which, as shown
      previously by others, are responsible for the concerted motion of simple fluids
      in molecular sieves. Additionally we prove here for the first time that, despite
      the narrow diameter of the carbon nanotubes considered which may suggest the
      existence of single-file diffusion, when the trajectories of confined water are
      studied at time scales in excess of 500 ps, a Fickian-type diffusion mechanism
      prevails. Our results are important for designing nano fluidic apparatuses to
      develop, for example, novel drug-delivery devices.

PMID- 16608258
TI  - Implications of the negative capacitance observed at forward bias in
      nanocomposite and polycrystalline solar cells.
AB  - Four different types of solar cells prepared in different laboratories have been
      characterized by impedance spectroscopy (IS): thin-film CdS/CdTe devices, an
      extremely thin absorber (eta) solar cell made with microporous
      TiO2/In(OH)xSy/PbS/PEDOT, an eta-solar cell of nanowire ZnO/CdSe/CuSCN, and a
      solid-state dye-sensitized solar cell (DSSC) with Spiro-OMeTAD as the transparent
      hole conductor. A negative capacitance behavior has been observed in all of them
      at high forward bias, independent of material type (organic and inorganic),
      configuration, and geometry of the cells studied. The experiments suggest a
      universality of the underlying phenomenon giving rise to this effect in a broad
      range of solar cell devices. An equivalent circuit model is suggested to explain
      the impedance and capacitance spectra, with an inductive recombination pathway
      that is activated at forward bias. The deleterious effect of negative capacitance
      on the device performance is discussed, by comparison of the results obtained for
      a conventional monocrystalline Si solar cell showing the positive chemical
      capacitance expected in the ideal IS model of a solar cell.

PMID- 16608259
TI  - Metallic photonic crystals based on solution-processible gold nanoparticles.
AB  - We demonstrate the fabrication of metallic photonic crystals, in the form of a
      periodic array of gold nanowires on a waveguide, by spin-coating a colloidal gold
      suspension onto a photoresist mask and subsequent annealing. The photoresist mask
      with a period below 500 nm is manufactured by interference lithography on an
      indium tin oxide (ITO) glass substrate, where the ITO layer has a thickness
      around 210 nm and acts as the waveguide. The width of the nanowires can be
      controlled from 100 to 300 nm by changing the duty cycle of the mask. During
      evaporation of solvent, the gold nanoparticles are drawn to the grooves of the
      grating with apparently complete dewetting off the photoresist for channels less
      than 2 microm in width, which therefore form nanowires after the annealing
      process. Strong coupling between the waveguide mode and the plasmon resonance of
      the nanowires, which is dependent on the polarization and incidence angle of the
      light wave, is demonstrated by optical extinction measurements. Continuity of the
      nanowires is confirmed by conductivity properties. Simplicity, high processing
      speed, and low cost are the main advantages of this method, which may have a
      plethora of applications in telecommunication, all-optical switching, sensors,
      and semiconductor devices.

PMID- 16608260
TI  - Atomistic simulations of electrowetting in carbon nanotubes.
AB  - Electrowetting of carbon nanotubes by mercury was studied using classical
      molecular dynamics simulations in conjunction with a macroscopic
      electrocapillarity model. A scaled ab initio mercury dimer potential, optimized
      to reproduce the mercury liquid density (at 300 K), melting point, and wetting
      angle on graphite, was selected for the simulations. Wetting of (20,20) single
      walled carbon nanotubes by mercury occurs above a threshold voltage of 2.5 V
      applied across the interface. Both the electrocapillary pressure and imbibition
      velocity increase quadratically with voltage and can acquire large values, for
      example, 2.4 kbar and 28 m/s at 4 V, indicating a notable driving force. The
      observed voltage scaling can be captured by the Lucas-Washburn equation modified
      to include a wetting-line friction term.

PMID- 16608261
TI  - Determining the size and shape dependence of gold nanoparticle uptake into
      mammalian cells.
AB  - We investigated the intracellular uptake of different sized and shaped colloidal
      gold nanoparticles. We showed that kinetics and saturation concentrations are
      highly dependent upon the physical dimensions of the nanoparticles (e.g., uptake
      half-life of 14, 50, and 74 nm nanoparticles is 2.10, 1.90, and 2.24 h,
      respectively). The findings from this study will have implications in the
      chemical design of nanostructures for biomedical applications (e.g., tuning
      intracellular delivery rates and amounts by nanoscale dimensions and engineering
      complex, multifunctional nanostructures for imaging and therapeutics).

PMID- 16608262
TI  - Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in
      living subjects.
AB  - We report the in vivo targeting and imaging of tumor vasculature using arginine
      glycine-aspartic acid (RGD) peptide-labeled quantum dots (QDs). Athymic nude mice
      bearing subcutaneous U87MG human glioblastoma tumors were administered QD705-RGD
      intravenously. The tumor fluorescence intensity reached maximum at 6 h
      postinjection with good contrast. The results reported here open up new
      perspectives for integrin-targeted near-infrared optical imaging and may aid in
      cancer detection and management including imaging-guided surgery.

PMID- 16608263
TI  - Design criteria for transparent single-wall carbon nanotube thin-film
      transistors.
AB  - A study based on two-dimensional percolation theory yielding quantitative
      parameters for optimum connectivity of transparent single-wall carbon nanotube
      (SWNT) thin films is reported. Optimum SWNT concentration in the filtrated
      solution was found to be 0.1 mg/L with a volume of 30 mL. Such parameters lead to
      SWNT fractions in the films of approximately Phi = 1.8 x 10(-3), much below the
      metallic percolation threshold, which is found to be approximately PhiC = 5.5 x
      10(-3). Therefore, the performance of transparent carbon nanotube thin-film
      transistors is limited by the metallic SWNTs, even below their percolation
      threshold. We show how this effect is related to hopping or tunneling between
      neighboring metallic tubes.

PMID- 16608264
TI  - Optical properties of star-shaped gold nanoparticles.
AB  - Here we report the synthesis, structure, and optical properties of ca. 100 nm
      star-shaped gold nanoparticles. Single particle spectroscopy measurements
      revealed that these nanoparticles have multiple plasmon resonances resulting in
      polarization-dependent scattering with multiple spectral peaks, which correspond
      to the different tips on the star-shaped structure. The plasmon resonances were
      also found to be extremely sensitive to the local dielectric environment.

PMID- 16608265
TI  - A multi-wall carbon nanotube tower electrochemical actuator.
AB  - Patterned multiwall carbon nanotube arrays up to four millimeters long were
      synthesized using chemical vapor deposition. Electrochemical actuation of a
      nanotube array tower was demonstrated in a 2 M NaCl solution at frequencies up to
      10 Hz with 0.15% strain using a 2 V square wave excitation. The synthesis and
      electrochemical modeling approach outlined in the paper provide a foundation for
      the design of nanotube smart materials that actuate and are load bearing.

PMID- 16608266
TI  - How to stabilize phospholipid liposomes (using nanoparticles).
AB  - The simple strategy of mixing phospholipid liposomes with charged nanoparticles
      and using sonication to mix them at low volume fraction produces particle
      stabilized liposomes that repel one another and do not fuse. Subsequently, the
      volume fraction can be raised as high as approximately 50%, reversibly, still
      without fusion. In studies of liposome longevity, we verified the stability of
      particle-stabilized liposome suspensions with volume fraction up to 16% for up to
      50 days, the longest period investigated. Fluorescent dyes were encapsulated
      within the particle-stabilized liposomes, without leakage. Although these
      particle-stabilized liposomes were stable against fusion, approximately 75% of
      the outer liposome surface remained unoccupied. This opens the door to using
      particle-stabilized liposomes in various applications.

PMID- 16608267
TI  - Atomic layer deposition on suspended single-walled carbon nanotubes via gas-phase
      noncovalent functionalization.
AB  - Alternating exposures of nitrogen dioxide gas and trimethylaluminum vapor are
      shown to functionalize the surfaces of single-walled carbon nanotubes with a self
      limited monolayer. Functionalized nanotube surfaces are susceptible to atomic
      layer deposition of continuous, radially isotropic material. This allows for the
      creation of coaxial nanotube structures of multiple materials with precisely
      controlled diameters. Functionalization involves only weak physical bonding,
      avoiding covalent modification, which should preserve the unique optical,
      electrical, and mechanical properties of the nanotubes.

PMID- 16608268
TI  - The state of strain in single GaN nanocolumns as derived from micro
      photoluminescence measurements.
AB  - In the present paper, studies on the state of strain in single and ensembles of
      nanocolumns investigated by photoluminescence spectroscopy will be presented. The
      GaN nanocolumns were either grown in a bottom-up approach or prepared in a top
      down approach by etching compact GaN layers grown on Si(111) and sapphire (0001)
      substrates. Experimental evidence for strain relaxation of the nanocolumns was
      found. The difference and development of the strain value for different
      nanocolumns could be verified by spatially resolved micro-photoluminescence on
      single nanocolumns separated from their substrate. A common D0X spectral position
      at 3.473 eV was found for all separated single GaN nanocolumns independent of the
      substrate or processing technique used, as expected for a relaxed system.

PMID- 16608269
TI  - Shape control of PbSe nanocrystals using noble metal seed particles.
AB  - We demonstrate that the shape of PbSe nanocrystals can be controlled
      systematically by seeding their growth with noble metal nanoparticles (Au, Ag, or
      Pd) and varying the seed and precursor concentrations. Cylinders (quantum rods),
      cubes, crosses, stars, and branched structures were produced in high yield at 150
      degrees C in reaction times of a few minutes. Although their absorption spectrum
      does not exhibit sharp features, the quantum rods exhibit significant
      photogeneration efficiency, enabling infrared sensitization of a polymeric
      photoconductive nanocomposite.

PMID- 16608270
TI  - Phase and polarization control as a route to plasmonic nanodevices.
AB  - We extend the concepts of phase, polarization, and feedback control of matter to
      develop a general approach for guiding light in the nanoscale via nanoparticle
      arrays. The phase and polarization of the excitation source are first introduced
      as tools for control over the pathway of light at array intersections. Genetic
      algorithms are next applied as a systematic design tool, wherein both the
      excitation field parameters and the structural parameters of the nanoparticle
      array are optimized to make devices with desired functionality. Implications to
      research fields such as single molecule spectroscopy, spatially confined
      chemistry, optical logic, and nanoscale sensing are envisioned.

PMID- 16608271
TI  - Colloidal CdSe quantum wires by oriented attachment.
AB  - We report here a relatively low temperature (100-180 degrees C) synthetic route
      to high-quality and single-crystalline CdSe nanowires using air-stable and
      generic chemicals. The diameter of nanowires was controlled and varied in an
      exceptionally small size regime, between 1.5 and 6 nm. This was achieved by using
      alkylamines, a single type or a mixture of two different types of amines, with
      different chain lengths and varying the reaction temperature. The experimental
      results suggest the coexistence of two types of fragments in the prewire
      aggregates, known as "pearl-necklace" or "string-of-pearls" in the literature,
      which are loosely associated and chemically fused sections.

PMID- 16608272
TI  - Fabrication and characterization of three-dimensional InGaAs/GaAs nanosprings.
AB  - This paper presents the use of a novel fabrication technique to produce three
      dimensional (3D) nanostructures. The process is based on conventional
      microfabrication techniques to create a planar pattern in an InGaAs/GaAs bilayer
      that self-assembles into 3D structures during a wet etch release. The
      nanostructures are proposed to function as nanosprings for electromechanical
      sensors. Nanomanipulation inside a scanning electron microscope (SEM) was
      conducted to probe the structures for mechanical characterization. The results
      were validated by simulation.

PMID- 16608273
TI  - Polymeric nanolayers as actuators for ultrasensitive thermal bimorphs.
AB  - Polymeric nanolayers are introduced here as active, thermal-stress mediating
      structures facilitating extremely sensitive thermal detection based upon the
      thermomechanical response of a bimaterial polymer-silicon microcantilever. To
      maximize the bimaterial bending effect, the microcantilever bimorph is composed
      of stiff polysilicon, with a strongly adhered polymer deposited via plasma
      enhanced chemical vapor deposition. The polymer layers with thickness ranging
      from 20 to 200 nm possess a rapid and pronounced response to temperature
      fluctuations due to intrinsic sensitive thermal behavior. We show that by taking
      advantage of the thermal stresses generated by the huge mismatch of material
      properties in the polymer-silicon bimorph, unprecedented thermal sensitivities
      can be achieved. In fact, the temperature resolution of our bimaterial
      microcantilevers approaches 0.2 mK with thermal sensitivity reaching 2 nm/mK;
      both parameters are more than an order of magnitude better than the current metal
      ceramic design. This new hybrid platform overcomes the inherently limited
      sensitivity of current sensor designs and provides the basis to develop the
      ultimate uncooled IR microsensor with unsurpassable sensitivity.

PMID- 16608274
TI  - Ferroelectric phase transition in individual single-crystalline BaTiO3 nanowires.
AB  - We report scanned probe characterizations of the ferroelectric phase transition
      in individual barium titanate (BaTiO3) nanowires. Variable-temperature
      electrostatic force microscopy is used to manipulate, image, and evaluate the
      diameter-dependent stability of ferroelectric polarizations. These measurements
      show that the ferroelectric phase transition temperature (TC) is depressed as the
      nanowire diameter (dnw) decreases, following a 1/dnw scaling. The diameter at
      which TC falls below room temperature is determined to be approximately 3 nm, and
      extrapolation of the data indicates that nanowires with dnw as small as 0.8 nm
      can support ferroelectricity at lower temperatures. We also present density
      functional theory (DFT) calculations of bare and molecule-covered BaTiO3
      surfaces. These calculations indicate that ferroelectricity in nanowires is
      stabilized by molecular adsorbates such as OH and carboxylates. These adsorbates
      are found to passivate polarization charge more effectively than metallic
      electrodes, explaining the observed stability of ferroelectricity in small
      diameter BaTiO3 nanowires.

PMID- 16608275
TI  - Mechanically tunable three-dimensional elastomeric network/air structures via
      interference lithography.
AB  - We show how to employ an interference lithographic template (ILT) as a facile
      mold for fabricating three-dimensional bicontinuous PDMS (poly(dimethylsiloxane))
      elastomeric structures and demonstrate the use of such a structure as a
      mechanically tunable PDMS/air phononic crystal. A positive photoresist was used
      to make the ILT, and after infiltration with PDMS, the resist was removed in a
      water-based basic solution which avoided PDMS swelling or pattern collapse
      occurring during the ILT removal process. Since the period of the structure is
      approximately 1 microm, the density of states of gigahertz phonons are altered by
      the phononic PDMS/air crystal. Brillouin light scattering (BLS) was employed to
      measure phononic modes of the structure as a function of mechanical strain. The
      results demonstrate that the phononic band diagram of such structures can be
      tuned mechanically.

PMID- 16608276
TI  - Subsurface Raman imaging with nanoscale resolution.
AB  - We report on chemically specific, subsurface imaging with high spatial
      resolution. Using tip-enhanced Raman spectroscopy, we probe carbon nanotubes
      buried beneath a host dielectric media. We demonstrate our ability to map and
      resolve specific vibrational modes with 30 nm spatial resolution for dielectric
      layers with different thicknesses.

PMID- 16608277
TI  - Surface water and the origin of the positive excess specific heat for 7 nm rutile
      and anatase nanoparticles.
AB  - Specific heats (15-350 K) have been measured on 7 nm TiO2 anatase and rutile
      nanoparticles containing significant amounts of surface-adsorbed water. By
      successively reducing the water content without changing particle size, we
      observed two types of water behavior. The specific heat of bare 7 nm particles
      was estimated using the water specific heats. Contrary to previous literature
      reports, the bare small particle specific heats are the same as those of the
      bulk, within experimental error.

PMID- 16608278
TI  - Local field effects on electron transport in nanostructured TiO2 revealed by
      terahertz spectroscopy.
AB  - We study electron mobilities in nanoporous and single-crystal titanium dioxide
      with terahertz time domain spectroscopy. This ultrafast technique allows the
      determination of the electron mobility after carrier thermalization with the
      lattice but before equilibration with defect trapping states. The mobilities
      reported here for single-crystal rutile (1 cm2/(V s)) and porous TiO2 (10(-2)
      cm2/(V s)) therefore represent upper limits for electron transport at room
      temperature for defect-free materials. The large difference in mobility between
      bulk and porous samples is explained using Maxwell-Garnett effective medium
      theory. These results demonstrate that electron mobility is strongly dependent on
      the material morphology in nanostructured polar materials due to local field
      effects and cannot be used as a direct measure of the diffusion coefficient.

PMID- 16608279
TI  - Observation of current reversal in the scanning tunneling spectra of fullerene
      like WS2 nanoparticles.
AB  - Current-voltage characteristics measured using STM on fullerene-like WS2
      nanoparticles show zero-bias current and contain segments in which the tunneling
      current flows opposite to the applied bias voltage. In addition, negative
      differential conductance peaks emerge in these reversed current segments, and the
      characteristics are hysteretic with respect to the change in the voltage sweep
      direction. Such unusual features resemble those appearing in cyclic
      voltammograms, but are uniquely observed here in tunneling spectra measured in
      vacuum, as well as in ambient and dry atmosphere conditions. This behavior is
      attributed to tunneling-driven electrochemical processes.

PMID- 16608280
TI  - Right bipyramids of silver: a new shape derived from single twinned seeds.
AB  - Silver nanoparticles with a single (111) twin were selectively nucleated and
      grown for the first time to produce right bipyramids 75-150 nm in edge length.
      Key to the production of single twinned seeds was the addition of NaBr to a
      polyol synthesis in which AgNO3 is reduced by ethylene glycol in the presence of
      poly(vinyl pyrrolidone). Examination of nanoparticles at different stages of the
      reaction with electron microscopy revealed that the spherical, single twinned
      seeds grew to become right bipyramids through enlargement of their (100) facets.
      The UV-vis-NIR spectrum exhibited by right bipyramids is distinct from that of
      any other silver nanostructure, and their sharp corners make these new
      nanoparticles especially promising for enhancement of Raman scattering.

PMID- 16608281
TI  - Ion coordinating sensitizer for high efficiency mesoscopic dye-sensitized solar
      cells: influence of lithium ions on the photovoltaic performance of liquid and
      solid-state cells.
AB  - A Li+ coordinating sensitizer, NaRu(4-carboxylic acid-4'-carboxylate)(4,4'
      bis[(triethylene glycol methyl ether) methyl ether]-2,2'-bipyridine)(NCS)2 (coded
      as K51), has been synthesized, and the effect of Li+ coordination on its
      performance in mesoscopic titanium dioxide dye-sensitized solar cells has been
      investigated. Fourier transform infrared spectra suggest that Li+ coordinates to
      the triethylene oxide methyl ether side chains on the dye molecules. With the
      addition of Li+ to a nonvolatile liquid electrolyte, we observe a significant
      increase in the photocurrent density, with only a small decrease in the open
      circuit voltage, contrary to a non ion coordinating dye which displays a large
      drop in potential with the addition of Li+. For a solar cell incorporating an
      organic hole-transporter, we find the potential rises with increasing the Li+
      concentration in the hole-transporter matrix. For the liquid electrolyte and
      solid-state cells, we obtain power conversion efficiencies of 7.8% and 3.8%,
      respectively, under simulated sunlight.

PMID- 16608282
TI  - Nanoscale resolved infrared probing of crystal structure and of plasmon-phonon
      coupling.
AB  - We show that slight variations of a crystal lattice cause significant spectral
      modifications of phonon-polariton resonant near-field interaction between polar
      semiconductor crystals and a scanning metal tip. Exploiting the effect for near
      field imaging a SiC polytype boundary, we establish infrared mapping of crystal
      structure and crystal defects at 20 nm spatial resolution (lambda/500). By
      spectroscopic probing of doped SiC polytypes, we find that phonon-polariton
      resonant near-field interaction is also sensitive to electronic properties due to
      plasmon-phonon coupling in the crystals.

PMID- 16608284
TI  - Thermooptical properties of gold nanoparticles embedded in ice: characterization
      of heat generation and melting.
AB  - We investigate the system of optically excited gold NPs in an ice matrix aiming
      to understand heat generation and melting processes at the nanoscale level. Along
      with the traditional fluorescence method, we introduce thermooptical spectroscopy
      based on phase transformation of a matrix. With this, we can not only measure
      optical response but also thermal response, that is, heat generation. After
      several recrystallization cycles, the nanoparticles are embedded into the ice
      film where the optical and thermal properties of the nanoparticles are probed.
      Spatial fluorescence mapping shows the locations of Au nanoparticles, whereas the
      time-resolved Raman signal of ice reveals the melting process. From the time
      dependent Raman signals, we determine the critical light intensities at which the
      laser beam is able to melt ice around the nanoparticles. The melting intensity
      depends strongly on temperature and position. The position-dependence is
      especially strong and reflects a mesoscopic character of heat generation. We
      think that it comes from the fact that nanoparticles form small complexes of
      different geometry and each complex has a unique thermal response. Theoretical
      calculations and experimental data are combined to make a quantitative measure of
      the amount of heat generated by optically excited Au nanoparticles and
      agglomerates. The information obtained in this study can be used to design
      nanoscale heaters and actuators.

PMID- 16608285
TI  - Shot noise measurements on a single molecule.
AB  - We report measurements of shot noise in the current through a single D2 molecule.
      The molecular junctions were formed by means of the mechanically controllable
      break junction technique. The configuration of the D2 molecule bridging the gap
      between two Pt tips is verified by use of point contact spectroscopy. Maintaining
      the same junction shot noise measurements were performed and the observed quantum
      suppression shows that conductance is carried dominantly by a single, almost
      fully transparent conductance channel. This observation allows us to decide
      between conflicting model calculations for this system, and this may serve as a
      benchmark for further computations on molecular junctions.

PMID- 16608283
TI  - Fast DNA sequencing via transverse electronic transport.
AB  - A rapid and low-cost method to sequence DNA would usher in a revolution in
      medicine. We propose and theoretically show the feasibility of a protocol for
      sequencing based on the distributions of transverse electrical currents of single
      stranded DNA while it translocates through a nanopore. Our estimates, based on
      the statistics of these distributions, reveal that sequencing of an entire human
      genome could be done with very high accuracy in a matter of hours without
      parallelization, that is, orders of magnitude faster than present techniques. The
      practical implementation of our approach would represent a substantial
      advancement in our ability to study, predict, and cure diseases from the
      perspective of the genetic makeup of each individual.

PMID- 16608286
TI  - Effect of the growth conditions on the spatial features of Re nanowires produced
      by directional solidification.
AB  - The effects of the solidification parameters, such as growth rate and temperature
      gradient, on the distance and diameter of Re nanowires have been examined. Both
      the spacing and diameter increase with decreasing growth rate and temperature
      gradient, respectively. The ratio of fiber spacing to diameter is 9.1. In
      addition, it was demonstrated that the temperature gradient influences interface
      undercooling in the same way as the growth rate and may be used as an additional
      parameter to control fiber spacing and diameter.

PMID- 16608288
TI  - A reversible molecular switch based on pattern-change in chlorobenzene and
      toluene on a Si(111)-(7x7) surface.
AB  - A reversible molecular switch is proposed, based on an observed change in a
      physisorbed pattern of chlorobenzene or toluene at Si(111)-(7x7), from
      "triangles" to "circles". Electronic excitation, at an applied surface voltage of
      Vs = -2.0 V, caused molecular migration, by one atomic site, from under the tip
      (switch "off"). Thereafter, the adsorbate pattern reverted thermally from circles
      to triangles (switch "on") across a measured activation barrier of Ea = 0.3 eV
      for chlorobenzene and 0.2 eV for toluene.

PMID- 16608287
TI  - Cellular effect of high doses of silica-coated quantum dot profiled with high
      throughput gene expression analysis and high content cellomics measurements.
AB  - Quantum dots (Qdots) are now used extensively for labeling in biomedical
      research, and this use is predicted to grow because of their many advantages over
      alternative labeling methods. Uncoated Qdots made of core/shell CdSe/ZnS are
      toxic to cells because of the release of Cd2+ ions into the cellular environment.
      This problem has been partially overcome by coating Qdots with polymers,
      poly(ethylene glycol) (PEG), or other inert molecules. The most promising coating
      to date, for reducing toxicity, appears to be PEG. When PEG-coated silanized
      Qdots (PEG-silane-Qdots) are used to treat cells, toxicity is not observed, even
      at dosages above 10-20 nM, a concentration inducing death when cells are treated
      with polymer or mercaptoacid coated Qdots. Because of the importance of Qdots in
      current and future biomedical and clinical applications, we believe it is
      essential to more completely understand and verify this negative global response
      from cells treated with PEG-silane-Qdots. Consequently, we examined the molecular
      and cellular response of cells treated with two different dosages of PEG-silane
      Qdots. Human fibroblasts were exposed to 8 and 80 nM of these Qdots, and both
      phenotypic as well as whole genome expression measurements were made. PEG-silane
      Qdots did not induce any statistically significant cell cycle changes and minimal
      apoptosis/necrosis in lung fibroblasts (IMR-90) as measured by high content image
      analysis, regardless of the treatment dosage. A slight increase in
      apoptosis/necrosis was observed in treated human skin fibroblasts (HSF-42) at
      both the low and the high dosages. We performed genome-wide expression array
      analysis of HSF-42 exposed to doses 8 and 80 nM to link the global cell response
      to a molecular and genetic phenotype. We used a gene array containing
      approximately 22,000 total probe sets, containing 18,400 probe sets from known
      genes. Only approximately 50 genes (approximately 0.2% of all the genes tested)
      exhibited a statistically significant change in expression level of greater than
      2-fold. Genes activated in treated cells included those involved in carbohydrate
      binding, intracellular vesicle formation, and cellular response to stress.
      Conversely, PEG-silane-Qdots induce a down-regulation of genes involved in
      controlling the M-phase progression of mitosis, spindle formation, and
      cytokinesis. Promoter analysis of these results reveals that expression changes
      may be attributed to the down-regulation of FOXM and BHLB2 transcription factors.
      Remarkably, PEG-silane-Qdots, unlike carbon nanotubes, do not activate genes
      indicative of a strong immune and inflammatory response or heavy-metal-related
      toxicity. The experimental evidence shows that CdSe/ZnS Qdots, if appropriately
      protected, induce negligible toxicity to the model cell system studied here, even
      when exposed to high dosages. This study indicates that PEG-coated silanized
      Qdots pose minimal impact to cells and are a very promising alternative to
      uncoated Qdots.

PMID- 16608289
TI  - Microfluidic system for planar patch clamp electrode arrays.
AB  - We present a microfluidic system integrated with disposable cell interface
      partitions for simultaneous patch clamp recordings. Glass-supported
      poly(dimethylsiloxane) (PDMS) partitions, having a 2 microm air-blown aperture,
      were reversibly sealed to a microfluidic system including PDMS channels with
      isolation valves and microfabricated Ag/AgCl electrodes. Gigaseal recordings from
      RBL-1 cells were obtained with a 24% success rate. Simultaneous whole cell
      recordings from valve-isolated electrodes were obtained.

PMID- 16608290
TI  - Manipulating Kondo temperature via single molecule switching.
AB  - Two conformations of isolated single TBrPP-Co molecules on a Cu(111) surface are
      switched by applying +2.2 V voltage pulses from a scanning tunneling microscope
      tip at 4.6 K. The TBrPP-Co has a spin-active cobalt atom caged at its center, and
      the interaction between the spin of this cobalt atom and free electrons from the
      Cu(111) substrate can cause a Kondo resonance. Tunneling spectroscopy data reveal
      that switching from the saddle to a planar molecular conformation enhances spin
      electron coupling, which increases the associated Kondo temperature from 130 to
      170 K. This result demonstrates that the Kondo temperature can be manipulated
      just by changing molecular conformation without altering chemical composition of
      the molecule.

PMID- 16608291
TI  - Superior wear resistance of aggregated diamond nanorods.
AB  - The hardness of single-crystal diamond is superior to all other known materials,
      but its performance as a superabrasive is limited because of its low wear
      resistance. This is the consequence of diamond's low thermal stability (it
      graphitizes at elevated temperature), low fracture toughness (it tends to cleave
      preferentially along the octahedral (111) crystal plains), and large directional
      effect in polishing (some directions appear to be "soft", i.e., easy to abrade,
      because diamond is anisotropic in many of its physical properties). Here we
      report the results of measurements of mechanical properties (hardness, fracture
      toughness, and Young's modulus) of aggregated diamond nanorods (ADNRs)
      synthesized as a bulk sample. Our investigation has shown that this
      nanocrystalline material has the fracture toughness 11.1 +/- 1.2 MPa.m(0.5),
      which exceeds that of natural and synthetic diamond (that varies from 3.4 to 5.0
      MPa.m(0.5)) by 2-3 times. At the same time, having a hardness and Young's modulus
      comparable to that of natural diamond and suppressed because of the random
      orientation of nanorods "soft" directions, ADNR samples show the enhancement of
      wear resistance up to 300% in comparison with commercially available
      polycrystalline diamonds (PCDs). This makes ADNRs extremely prospective materials
      for applications as superabrasives.

PMID- 16608292
TI  - Nanorice: a hybrid plasmonic nanostructure.
AB  - We have designed and fabricated a new hybrid nanoparticle that combines the
      intense local fields of nanorods with the highly tunable plasmon resonances of
      nanoshells. This dielectric core-metallic shell prolate spheroid nanoparticle
      bears a remarkable resemblance to a grain of rice, inspiring the name "nanorice".
      This geometry possesses far greater structural tunability than either a nanorod
      or a nanoshell, along with much larger local field intensity enhancements and far
      greater sensitivity as a surface plasmon resonance (SPR) nanosensor than any
      dielectric-metal nanostructures reported previously. Invoking the plasmon
      hybridization picture allows us to understand the plasmon resonances of this
      geometry, as arising from a hybridization of the primitive plasmons of a solid
      spheroid and an ellipsoidal cavity inside a continuous metal.

PMID- 16608293
TI  - Plasmonic properties of supported Pt and Pd nanostructures.
AB  - The plasmonic properties of nanodisk arrays of Pt, Pd, and, for comparison, Ag
      are studied over a large size and spectral range and analyzed theoretically by an
      electrostatic model. Pt and Pd nanodisks exhibit broad localized surface plasmons
      with a higher sensitivity of the plasmon to the disk aspect ratio compared to Ag.
      Extinction cross-sections are generally about 50% smaller for Pt and Pd. The
      spectral plasmon positions, line-widths, and extinction cross-sections are well
      reproduced by the model.

PMID- 16608294
TI  - Near-field electrospinning.
AB  - A near-field electrospinning (NFES) process has been developed to deposit solid
      nanofibers in a direct, continuous, and controllable manner. A tungsten electrode
      with tip diameter of 25 microm is used to construct nanofibers of 50-500 nm line
      width on silicon-based collectors while the liquid polymer solution is supplied
      in a manner analogous to that of a dip pen. The minimum applied bias voltage is
      600 V, and minimum electrode-to-collector distance is 500 microm to achieve
      position controllable deposition. Charged nanofibers can be orderly collected,
      making NFES a potential tool in direct write nanofabrication for a variety of
      materials.

PMID- 16608295
TI  - Continuous distribution of emission states from single CdSe/ZnS quantum dots.
AB  - The photoluminescence dynamics of colloidal CdSe/ZnS/streptavidin quantum dots
      were studied using time-resolved single-molecule spectroscopy. Statistical tests
      of the photon-counting data suggested that the simple "on/off" discrete state
      model is inconsistent with experimental results. Instead, a continuous emission
      state distribution model was found to be more appropriate. Autocorrelation
      analysis of lifetime and intensity fluctuations showed a nonlinear correlation
      between them. These results were consistent with the model that charged quantum
      dots were also emissive, and that time-dependent charge migration gave rise to
      the observed photoluminescence dynamics.

PMID- 16608296
TI  - Nano fountain pen manufacture of polymer lenses for nano-biochip applications.
AB  - Polymer microlenses have been manufactured by delivering droplets of a monomer
      mixture to a glass substrate using a nano fountain pen (NFP). Subsequent UV
      polymerization yielded microlenses with optical properties that were controlled
      by varying the deposition time of the monomer solution. Using this approach, it
      is possible to strategically place single microlenses at predefined positions
      with very high accuracy, an ability which may prove very useful for nano-biochip
      applications, as demonstrated.

PMID- 16608297
TI  - Nanospring pressure sensors grown by glancing angle deposition.
AB  - Arrays of Cr zigzag nanosprings and slanted nanorods, 15-55 nm and 40-80-nm-wide,
      respectively, were grown on SiO2/Si substrates by glancing angle deposition. The
      arrays exhibit a reversible change in resistivity upon loading and unloading, by
      50% for nanosprings and 5% for nanorods, indicating their potential as pressure
      sensors. The resistivity drop is due to a compression of nanosprings (by a
      measured 19% for an applied external force of 10(-10) N per spring), which causes
      them to physically touch their neighbors, providing a path for electric current
      to flow between nanosprings. Repeated loading and unloading at large loads (> or
      =1 MPa) results in irreversible plastic deformation and a degradation of the
      pressure sensitivity.

PMID- 16608298
TI  - Deterministic positioning of three-dimensional structures on a substrate by film
      growth.
AB  - A process to fabricate three-dimensional crystalline structures at controlled
      locations on a substrate during film growth and annealing is demonstrated. Low
      energy electron microscopy reveals that silver is transported to regions on a
      tungsten surface with closely spaced atomic steps. By controlling the substrate
      topography using a focused ion beam to machine small holes, this general
      mechanism produces an array of cylinders as a silver film dewets the substrate.

PMID- 16608299
TI  - Optical interference from pairs and arrays of nanowires.
AB  - The angle dependence of the scattered light from pairs and one-dimensional arrays
      of nanowires was studied. The intensity of the scattered light varied distinctly
      during rotation of the structure. The results could be theoretically modeled by
      treating a pair of nanowires as a double slit and an array of nanowires as a
      grating. The correspondence between theory and experimental results conclusively
      proves that the variations are due to the proposed interference effects.

PMID- 16608300
TI  - Toxicological impact studies based on Escherichia coli bacteria in ultrafine ZnO
      nanoparticles colloidal medium.
AB  - We report here preliminary studies of biocidal effects and cellular
      internalization of ZnO nanoparticles on Escherichia coli bacteria. ZnO
      nanoparticles were synthesized in di(ethylene glycol) (DEG) medium by forced
      hydrolysis of ionic Zn2+ salts. Particle size and shape were controlled by
      addition of small molecules and macromolecules such as tri-n-octylphosphine
      oxide, sodium dodecyl sulfate, polyoxyethylene stearyl ether, and bovine serum
      albumin. Transmission electron microscopy (TEM) and X-ray diffraction analyses
      were used to characterize particle structure, size, and morphology. Bactericidal
      tests were performed in Luria-Bertani medium on solid agar plates and in liquid
      systems with different concentrations of small and macromolecules and also with
      ZnO nanoparticles. TEM analyses of bacteria thin sections were used to study
      biocidal action of ZnO materials. The results confirmed that E. coli cells after
      contact with DEG and ZnO were damaged showing a Gram-negative triple membrane
      disorganization. This behavior causes the increase of membrane permeability
      leading to accumulation of ZnO nanoparticles in the bacterial membrane and also
      cellular internalization of these nanoparticles.

PMID- 16608301
TI  - Direct demonstration of decoupling of spin and charge currents in nanostructures.
AB  - The notion of decoupling of spin and charge currents is one of the basic
      principles underlying the rapidly expanding field of spintronics. However, no
      direct demonstration of the phenomenon exists. We report a novel measurement in
      which a nonequilibrium spin population is created by a pointlike injection of
      current from a ferromagnet across a tunnel barrier into a one-dimensional spin
      channel and detected differentially by a pair of ferromagnetic electrodes placed
      symmetrically about the injection point. We demonstrate that the spin current is
      strictly isotropic about the injection point and, therefore, completely decoupled
      from the unidirectional charge current.

PMID- 16608302
TI  - A general approach to binary and ternary hybrid nanocrystals.
AB  - We describe and demonstrate a general strategy for engineering binary and ternary
      hybrid nanoparticles based on spontaneous epitaxial nucleation and growth of a
      second and third component onto seed nanoparticles in high-temperature organic
      solutions. Multifunctional hybrid nanoparticles that combine magnetic, plasmonic,
      and semiconducting properties and that are tunable in size and morphology can be
      realized, as demonstrated for combinations of Au, Fe3O4 and PbS or PbSe. The
      properties of each component within the hybrids can be modulated strongly by the
      conjugating component(s) aided by the coherent interfaces between them.

PMID- 16608303
TI  - Nanoporous gold prism microassembly through a self-organizing route.
AB  - We report a simple and spontaneous synthesis of a nanoporous gold prism
      microassembly with highly dense skins, which is achieved just by immersing
      nanoporous gold into concentrated hydrochloric acid. The ligament size was
      coarsened to several hundred nanometers, but the crystal face orientation was
      still preserved. The same trends were seen in the case of coarsening by
      annealing; however, the morphology of the nanoporous gold prism microassembly was
      significantly different from the annealed nanoporous gold.

PMID- 16608304
TI  - Resolving electron transfer kinetics at the nanocrystal/solution interface.
AB  - The kinetics of electron transfer between individual gold nanocrystals and a
      solution redox species is quantified. The observed rate is dependent on the
      extent of electronic coupling between nanocrystals in the monolayer indicating
      the effect of Coulomb blockade on electrochemical kinetics.

PMID- 16608306
TI  - A photo-hydrogen-evolving molecular device driving visible-light-induced EDTA
      reduction of water into molecular hydrogen.
AB  - A photo-hydrogen-evolving molecular device made up of a tris(2,2'
      bipyridine)ruthenium(II) derivative and a dichloro(2,2'-bipyridine)platinum(II)
      derivative has been found to serve as the first effective model of a "molecular
      device" which evolves molecular hydrogen from water in the presence of a
      sacrificial electron donor (EDTA), under the visible-light illumination.

PMID- 16608305
TI  - Complexation, structure, and superoxide dismutase activity of the imidazolate
      bridged dinuclear copper moiety with beta-cyclodextrin and its guanidinium
      containing derivative.
AB  - An imidazolate-bridged homodinuclear complex, {[Cu(L)(H2O)]2(im)}(ClO4)3 (1),
      assembled with beta-cyclodextrin (betaCD) and its guanidinium-containing
      derivative (betaGCD), and thus a helical inclusion complex,
      {[Cu(L)(H2O)(betaCD)]2(im)}(ClO4)3 (2), were successfully isolated and
      structurally characterized. Structural analysis showed that each Cu(II) ion has a
      distorted square pyramidal N4Ow coordination sphere and forms a chiral chain
      through hydrogen-bonding and hydrophobic interactions. The UV-vis data showed
      that such a chain can provide the imidazolate bridge additional stability and
      results in the dissociation equilibrium taking place at the physiological pH. The
      obtained IC50 value for 2 (0.23 muM) showed a high superoxide dismutase (SOD)
      activity, which corresponds to a highly stable imidazolate bridge. Interestingly,
      the guanidinium-containing 1/betaGCD system showed higher SOD activity (IC50 =
      0.16 muM), which is enhanced at least by 30% in comparison with that of
      guanidinium-lacking 2. This result supports that the positive guanidinium plays a
      role in the catalytic mechanism of Cu,Zn-SOD by ensuring that superoxide enters
      and peroxide leaves rapidly from the coordination sphere of the copper ion.

PMID- 16608307
TI  - Gate-planarized low-operating voltage organic field-effect transistors enabled by
      hot polymer pressing/embedding of conducting metal lines.
AB  - A new process for fabricating patterned, gate-planarized organic field-effect
      transistors (OFETs) based on hot polymer pressing/embedding of conducting metal
      features is demonstrated. This methodology is applicable to a variety of gate
      conductors and polymer matrices. Vapor-deposited Al and Au and printed Ag lines
      as narrow as 15 mum are transferred from a substrate donor to the hot-pressed
      polymer, resulting in a new smooth, flat, self-planarized gate-plastic substrate
      composite on which thin polymer insulators can be spin-coated with great
      uniformity. OFETs fabricated on these structures with both p- and n-type
      semiconductors function at low voltages, opening new routes to printed electronic
      circuits and products.

PMID- 16608308
TI  - Experimental investigation of particle-assisted wetting.
AB  - In principle, one might prepare thin polymer membranes in an easy and economic
      way by generating a wetting layer of a polymerizable oil on a water surface,
      solidifying it, and transferring it to a solid substrate. However, there is
      hardly any oil that wets a water surface. One efficient way to assist the wetting
      of the water surface by an oil is to mix the oil with suitable particles.
      Theoretically, one expects several scenarios, which depend on the contact angles
      of the particles with the liquid interfaces. On the basis of these calculations,
      one can draw phase diagrams of particle-assisted wetting. In the current paper,
      we verify such a phase diagram of particle-assisted wetting experimentally.

PMID- 16608309
TI  - Direct nucleophilic acylation of nitroalkenes promoted by a fluoride
      anion/thiourea combination.
AB  - The direct nucleophilic acylation of nitroalkenes is reported utilizing a
      fluoride-initiated rearrangement of protected thiazolium carbinols. The key
      combination of fluoride anion and thiourea accesses carbonyl anion reactivity
      without the use of amine or amide bases typically employed in the generation of
      these Umpolung nucleophiles. The mild reaction conditions used to generate the
      reactive carbonyl anion species in situ allow for conjugate additions in good
      yield to sensitive nitroalkene electrophiles. The process is tolerant of a
      variety of thiazolium carbinols and nitroalkene substrates and can be rendered
      enantioselective and diastereoselective by the addition of a chiral thiourea
      derived from quinine.

PMID- 16608310
TI  - Reversible redox behavior between stannole dianion and bistannole-1,2-dianion.
AB  - The reversible redox behavior between the stannole dianion and the bistannole-1,2
      dianion is demonstrated. Reaction of the stannole dianion with oxygen (1 eq)
      gives the 1,2-bistannole-1,2-dianion which is a tin-analogue of the
      cyclopentadienyl anion in 94% yield. Reaction of the stannole dianion with
      ferrocenium tetrafluoroborate (1 eq) also gives the 1,2-dianion. The 1,2
      bistannole-1,2-dianion has a nonaromatic nature as evidenced by X-ray and NMR
      analysis. Reduction of the 1,2-dianion with lithium gives the starting dianion.

PMID- 16608311
TI  - Enantioselective total synthesis of bistramide A.
AB  - The enantioselective synthesis of bistramide A has been achieved with a longest
      linear sequence of 18 steps. The synthetic strategy involves the use of a
      distereoselective glycolate alkylation, an aldol addition of a chlorotitanium
      enolate of N-acylthiazolidinthione, and a Sharpless asymmetric epoxidation to
      synthesize the three key fragments.

PMID- 16608312
TI  - A mixed-valent ruthenium-oxo oxalato cluster Na7[Ru4(mu3-O)4(C2O4)6] with potent
      anti-HIV activities.
AB  - A structurally characterized mixed-valent tetranuclear ruthenium-oxo oxalato
      cluster exhibits anti-viral activities toward R5- and X4-tropic HIV-1, and
      possesses cytoprotective activity toward HIV-1 infected cells.

PMID- 16608313
TI  - Highly enantioselective addition of Me2Zn to aldehydes catalyzed by ClCr(Salen).
AB  - High enantiomeric excesses are obtained in the addition of Me2Zn catalyzed by
      commercially available ClCr(Salen). Broad scope, simple procedure, room
      temperature, low catalyst loading are the characteristics of this new
      enantioselective process, which uses the rather unreactive Me2Zn. Enantiomeric
      excesses in the range of 71-99% are obtained with all the aldehydes tested.

PMID- 16608314
TI  - Sequential rearrangement of 1,2,4Z,7-tetraenes involving [1,5]-hydrogen migration
      and electrocyclization: an efficient synthesis of eight-membered cyclic
      compounds.
AB  - An efficient protocol for the synthesis of eight-membered bicyclic compounds from
      the cycloisomerization of 1,2,4Z,7-tetraenes has been established. The possible
      intermediate for this transformation was trapped by its Diels-Alder reaction with
      N-ethyl maleimide. Thus the reaction may proceed via the sequential processes
      involving [1,5]-hydrogen migration and electrocyclization.

PMID- 16608315
TI  - Preparation of highly dispersed core/shell-type titania nanocapsules containing a
      single Ag nanoparticle.
AB  - Core/shell-type titania nanocapsules containing a single Ag nanoparticle were
      prepared. Ag nanoparticles were prepared using the reduction of silver nitrate
      with hydrazine in the presence of cetyltrimethylammonium bromide (CTAB) as
      protective agent. The sol-gel reaction of titanium tetraisopropoxide (TTIP) was
      used to prepare core/shell-type titania nanocapsules with CTAB-coated Ag
      nanoparticles as the core. TEM observations revealed that the size of the core
      (Ag particle) and the thickness of the shell (titania) of the core/shell
      particles obtained are about 10 nm and 5-10 nm, respectively. In addition, the
      nanocapsules were found to be dispersed in the medium as individual particles
      without aggregation. Moreover, titania coating caused the surface plasmon
      absorption of Ag nanoparticles to shift toward the longer wavelength side.

PMID- 16608317
TI  - Does urea denature hydrophobic interactions?
AB  - It is generally accepted that clusters of hydrophobic moieties in water fall
      apart when urea is added in substantial amounts. We performed atomistic molecular
      dynamics simulations of hydrophobic solute pairs and found evidence that urea
      molecules act as "glue" bridging these pairs thereby holding them together. The
      picture is quite general as it applies to aliphatic-aliphatic as well as aromatic
      aromatic interactions. The implications of this finding on the role of urea as a
      protein denaturant are discussed.

PMID- 16608316
TI  - Synthesis of indoles via 6pi-electrocyclic ring closures of trienecarbamates.
AB  - A new method for the preparation of indoles from readily available alpha
      haloenones and alpha-(trialkylstannyl)enecarbamates is described. Following a
      Stille coupling, trienecarbamate 2 is electronically activated to undergo a
      facile 6pi-electrocyclic ring closure and subsequent oxidation to afford
      protected aniline 4. Upon deprotection and reductive amination, acid 5 underwent
      clean cyclization to N-acetylindole 6 (Ac2O, NEt3, 130 degrees C). This method
      has been used to construct a variety of substituted indoles that are not easily
      prepared by conventional indole annelation methods.

PMID- 16608318
TI  - Communicating chemical congregation: a molecular AND logic gate with three
      chemical inputs as a "lab-on-a-molecule" prototype.
AB  - We demonstrate the first three-input molecular AND logic gate based on three
      chemical inputs as a direct way of detecting congregations of chemical species.
      The AND gate operates in water and responds to Na+, H+, and Zn2+ inputs with an
      enhanced fluorescence signal when pre-set concentration thresholds are exceeded.
      Future "lab-on-a-molecule" devices could have application in medicine for rapid
      disease screening.

PMID- 16608319
TI  - Distributions of conduction electrons as manifested in MAS NMR of gallium
      nitride.
AB  - A strategy is demonstrated for identifying unambiguously and characterizing
      quantitatively the effects of distributions of conduction electron concentrations
      arising from intentional or unintentional dopants in semiconductors by magic
      angle spinning (MAS) NMR. The 71Ga MAS NMR spectra of a number of chemically
      synthesized GaN samples with no intentional doping show inhomogeneously broadened
      absorptions to high frequency of the main peak. These broad signals are shown,
      from spin-lattice relaxation time measurements as a function of shift position in
      a single sample, to be due to Knight shifts arising from degenerate conduction
      electrons. For a GaN sample with Ge as an intentional dopant at the 0.13% (wt)
      level, the spectrum is dramatically broadened and shifted to high frequency by up
      to several hundred parts per million. Analysis of the inhomogeneously broadened
      line shape yields a quantitative probability density function for electron
      carrier concentration in the bulk sample that reflects significant compositional
      heterogeneity due to a variety of possible sources.

PMID- 16608320
TI  - A gold nanoparticle based approach for screening triplex DNA binders.
AB  - Nanoparticle assemblies interconnected with DNA triple helixes can be used to
      colorimetrically screen for triplex DNA binding molecules and simultaneously
      determine their relative binding affinities based on melting temperatures.
      Nanoparticles assemble only when DNA triple helixes form between DNA from two
      different particles and a third strand of free DNA. In addition, the triple helix
      structure is unstable at room temperature and only forms in the presence of
      triplex DNA binding molecules which stabilize the triple helix. The resulting
      melting transition of the nanoparticle assembly is much sharper and at a
      significantly higher Tm than the analogous triplex structure without
      nanoparticles. Upon nanoparticle assembly, a concomitant red-to-blue color change
      occurs. The assembly process and color change do not occur in the presence of
      duplex DNA binders and therefore provide a significantly better screening process
      for triplex DNA binding molecules compared to standard methods.

PMID- 16608321
TI  - Characterization of the terminal iron(IV) imides [[PhBP(t)(Bu)2(pz')]Fe(IV)NAd]+.
AB  - New hybrid bis(phosphine)(pyrazole)borate tripodal ligands ([PhBPtBu2(pz')]-) are
      reported that support pseudotetrahedral iron in the oxidation states +1, +2, +3,
      and +4. The higher oxidation states are stabilized by a terminal FeNR linkage. Of
      particular interest is the generation and thorough characterization of an S = 1
      FeIVNR+ imide cation using this new ligand system. The latter species can be
      observed electrochemically and spectroscopically, and its solid-state crystal
      structure is reported.

PMID- 16608322
TI  - Amphiphilic gold nanoparticles with V-shaped arms.
AB  - Here we describe a very efficient method to produce well-defined amphiphilic gold
      nanoparticles (Au NPs) with an equal number of hydrophobic and hydrophilic arms
      which are distributed along the surface of a 2-nm gold core in an alternating
      fashion. The strategy involves direct coupling of V-shaped block copolymer
      amphiphile 2 with a carboxylic group at its junction point to mercaptophenol
      terminated Au NPs. The reaction proceeds under mild esterification conditions and
      yields the product with a molecular weight of 40 kDa, high grafting density (2.9
      chains/nm2), and extremely low polydispersity (1.07). The big advantage of this
      approach is the opportunity to avoid the use of expensive and often inaccessible
      polymeric thiols. The method described here is applicable to any carboxyl
      terminated molecules and can be used for the preparation of complex, yet well
      defined, macromolecular hybrid structures such as 1 (Au(PB-PEG)n). The new
      product, which was characterized by a combination of SEC, NMR, UV-vis, DLS, and
      TEM, represents a unique example of gold nanoparticles soluble in any
      conventional solvent.

PMID- 16608323
TI  - A non-steroidal facial amphiphile.
AB  - This paper gives the synthesis of an unusual non-steroidal amphiphile consisting
      of a large rigid molecule that possesses two water-solubilizing sulfates on one
      face and an extended hydrophobic surface on the other. The properties of this
      compound have been examined by X-ray analysis, light and cryo-electron
      microscopy, surface tension, conductivity, microrheology, and NMR. Aqueous
      solutions behave quite differently from those of a conventional amphiphile with
      long linear and flexible chains (e.g., sodium dodecyl sulfate). Thus, there is
      evidence that the facial amphiphile self-assembles to form viscous networks, but
      without the traditional critical micelle concentration, as if assembly is a
      stepwise process. Emulsions of toluene in water promoted by the facial amphiphile
      are stable for many months. In contrast to conventional surfactants, the NMR
      peaks are obliterated in aqueous solutions of the facial amphiphile. Both X-ray
      and cryo-HRSEM data suggest a lamellar morphology.

PMID- 16608324
TI  - Gyroscope-like molecules consisting of PdX2/PtX2 rotators encased in three-spoke
      stators: synthesis via alkene metathesis, and facile substitution and
      demetalation.
AB  - Reactions of trans-MCl2(P((CH2)6(CH=CH2)3)2 (M = a, Pd; b, Pt) and Grubbs'
      catalyst, followed by hydrogenation (ClRh(PPh3)3), give the title compounds trans
      MCl2(P((CH2)14)3P) (2a, 37%; 2b, 43%). These react with LiBr, NaI, and KCN to
      give the corresponding MBr2, MI2, and M(CN)2 species (58-99%). 13C NMR data show
      that the MX2 moieties rapidly rotate within the diphosphine cage on the NMR time
      scale, even at -120 degrees C. The reaction of 2b and KSCN gives separable
      Pt(SCN)2 and Pt(SCN)(NCS) species (5b, 27%; 6b, 30%), and that with Ph2Zn gives a
      PtPh2 species (7b, 55%). NMR data for 5b-7b show that MX2 rotation is no longer
      rapid. Reactions of 2b with excess NaCCH or KCN afford the free dibridgehead
      diphosphine P((CH2)14)3P (66-83%), presumably as an "in/in" isomer, as addition
      of PtCl2 regenerates 2b. The crystal structures of 2a and 7b are analyzed with
      respect to MX2 rotation.

PMID- 16608325
TI  - The syn-oriented 2-OH provides a favorable proton transfer geometry in 1,2-diol
      monoester aminolysis: implications for the ribosome mechanism.
AB  - A computational study of 1-formyl 1,2-ethanediol aminolysis predicts a stepwise
      mechanism involving syn-2-OH-assisted proton transfer. The syn-oriented 2-OH
      takes over the catalytic role of the external water or amine molecule previously
      observed in 2-deoxy ester aminolysis. It provides more favorable, that is, more
      linear, proton transfer geometry for the rate-limiting transition state resulting
      in an almost billion-fold rate acceleration of the overall reaction. These
      findings provide structural basis for explanation of the efficiency of the proton
      shuttling mechanism and imply double proton transfer catalysis by peptidyl tRNA
      A76 2'-OH as a possible catalytic strategy used by ribosome.

PMID- 16608326
TI  - Organocatalytic direct michael reaction of ketones and aldehydes with beta
      nitrostyrene in brine.
AB  - We have developed a direct, asymmetric Michael reaction that can be performed in
      brine or seawater without addition of organic solvents. A bifunctional catalyst
      with long hydrophobic alkyl chains efficiently catalyzed Michael reactions and
      afforded the desired products in excellent yield with high enantiomeric excess,
      even when only an equal molar ratio of the donor to acceptor was used.

PMID- 16608327
TI  - Micelle directed synthesis of polyoxometalate nanoparticles and their improved
      catalytic activity for the aerobic oxidation of sulfides.
AB  - Micelle directed polyoxometalate nanoparticles were synthesized by depositing
      H3+xPVxMo12-xO40 (x = 0, 2) by precipitation on micelles prepared from cesium
      dodecyl sulfate. The cryo-TEM image showed particles of about approximately 10 nm
      roughly consistent with the particle size computed from an idealized model. HRTEM
      coupled with EELS imaging to map the distribution of the elements also supported
      the formation of micelle directed polyoxometalate nanoparticles. In the aerobic
      oxidation of various sulfides to sulfoxides and sulfones, the clustered
      polyoxometalate assemblies supported on hydrophilic silica showed significantly
      higher catalytic activity versus that of nonclustered assemblies.

PMID- 16608328
TI  - Correlation between HOMO alignment and contact resistance in molecular junctions:
      aromatic thiols versus aromatic isocyanides.
AB  - Understanding electron transport in metal-molecule-metal (MMM) junctions is of
      great importance for the advancement of molecular electronics. Critical factors
      that determine conductivity in a MMM junction include the nature of metal
      molecule contacts and the electronic structure of the molecular backbone. We have
      studied the electronic transport property and the valence electronic structure on
      rigid, conjugated oligoacenes of increasing length with either thiol (-S) or
      isocyanide (-CN) linkers using conducting probe atomic force microscopy (CP-AFM)
      and ultraviolet photoelectron spectroscopy (UPS). We find that for these
      conjugated systems the Au-CN contact is more resistive than Au-S. The difference
      in contact resistance correlates with UPS measurements that show the highest
      occupied molecular orbital (HOMO) of the isocyanide series is lower in energy
      (relative to the Fermi level of Au) than the HOMO of the thiol series, indicating
      the presence of a higher tunneling barrier at the contact for the isocyanide
      linked molecules. By contrast, the difference in the HOMO positions for the two
      series of molecules does not appear to affect the length dependence of the
      junction resistance (i.e., the beta value = 0.5 A-1).

PMID- 16608329
TI  - Room temperature palladium-catalyzed 2-arylation of indoles.
AB  - This communication describes the rational development of a PdII-catalyzed method
      for the direct 2-arylation of indoles using [Ar-IIII-Ar]BF4. These reactions
      proceed under remarkably mild conditions (often at room temperature and in the
      presence of ambient air and moisture), and these features are believed to be the
      result of a PdII/IV mechanism operating in these systems. These transformations
      can be used to prepare functionally diverse 2-arylated indoles and pyrroles, and
      their potential utility has been expanded by the development of an in situ
      procedure for generating the iodine(III) arylating reagents.

PMID- 16608330
TI  - Quantitative measurement of molecular diffusion coefficients by NMR spectroscopy.
AB  - An offset-independent adiabatic inversion pulse is used in the diffusion
      experiment to uniformly excite a sample region that is sufficiently long to
      ignore the ending effects, yet is short enough to have a homogeneous RF field and
      to represent the pulsed field gradient with a linear approximation. Under these
      conditions, the diffusion decay of the peak intensity appears to be Gaussian as a
      function of the effective gradient field ge as if all the molecules inside the
      selected region experienced the same ge. Quantitative measurement of molecular
      diffusion coefficients is therefore made possible.

PMID- 16608331
TI  - Palladium-catalyzed intermolecular alpha-arylation of zinc amide enolates under
      mild conditions.
AB  - The intermolecular alpha-arylation and vinylation of amides by palladium
      catalyzed coupling of aryl bromides and vinyl bromides with zinc enolates of
      amides is reported. Reactions of three different types of zinc enolates have been
      developed. The reactions of aryl halides occur in high yields with isolated
      Reformatsky reagents generated from alpha-bromo amides, with Reformatsky reagents
      generated in situ from alpha-bromo amides, and with zinc enolates generated by
      quenching lithium enolates of amides with zinc chloride. This use of zinc
      enolates, instead of alkali metal enolates, greatly expands the scope of amide
      arylation. The reactions occur at room temperature or 70 degrees C with
      bromoarenes containing cyano, nitro, ester, keto, fluoro, hydroxyl, or amino
      functionality and with bromopyridines. Moreover, the reaction has been developed
      with morpholine amides, the products of which are precursors to ketones and
      aldehydes. The arylation of zinc enolates of amides was conducted with catalysts
      bearing the hindered pentaphenylferrocenyl di-tert-butylphosphine (Q-phos) or the
      highly reactive, dimeric, Pd(I) complex [[P(t-Bu)3]PdBr]2.

PMID- 16608332
TI  - Insulin capture by an insulin-linked polymorphic region G-quadruplex DNA
      oligonucleotide.
AB  - Insulin capture by a G-quadruplex DNA oligonucleotide containing a two-repeat
      sequence of the insulin-linked polymorphic region (ILPR) of the human insulin
      gene promoter region is reported. The immobilized oligonucleotide was
      demonstrated to capture human insulin from standard solutions and from nuclear
      extracts of pancreatic cells with high selectivity, using affinity MALDI mass
      spectrometry and affinity capillary chromatography. Insulin was preferentially
      captured by the two-repeat ILPR oligonucleotide over another G-quadruplex-forming
      oligonucleotide, the thrombin-binding aptamer, as well as over a single repeat of
      the ILPR sequence that is not capable of forming the G-quadruplex architecture.
      Binding was shown to involve the beta chain of insulin. The discovery raises the
      possibility that insulin may bind to G-quadruplex DNA formed in the ILPR in vivo
      and thereby play a role in modulation of insulin gene expression, and it provides
      a basis for design of insulin analogues to probe this hypothesis. The
      availability of a DNA ligand to human insulin has analytical importance as well,
      offering an alternative to antibodies for in vitro or in vivo detection and
      sensing of insulin as well as its isolation and purification from biological
      samples.

PMID- 16608333
TI  - Analysis of human telomerase activity and function by two color single molecule
      coincidence fluorescence spectroscopy.
AB  - Telomerase is a nonclassical DNA polymerase that uses its integral RNA as a
      template to synthesize telomeric repeats onto chromosome ends. The molecular
      mechanism of telomerase is unique and involves a translocation step after the
      synthesis of each telomeric repeat. To directly measure the enzymatic turnover of
      substrate and the efficiency of the translocation step we have extended our two
      color single molecule fluorescence coincidence method (Anal.Chem. 2003, 75, 1664
      1670). The method employs Cy5-dATP incorporation into a DNA primer that has been
      prelabeled with a reference fluorophore. Measurements are performed in the single
      molecule regime and products, which necessarily have both fluorophores, are
      excited by two independent lasers, and give rise to coincident events. By
      counting the number of coincident events and using the coincidence detection
      efficiency, it is possible to determine the number of the extended products
      generated by attomole quantities of telomerase, without separation or the use of
      PCR or radioactivity. Histograms of the logarithms of the ratios of the Cy5 to
      the reference fluorophore fluorescence can be used to determine the length
      distribution of the products and hence the enzyme processivity. The mean
      processivity obtained from the single molecule fluorescence coincidence assay is
      0.32 +/- 0.04, in good agreement with the value of 0.37 +/- 0.05 derived from the
      direct radioactive assay approach. The function of the alignment domain of human
      telomerase RNA in sustaining catalytic activity in vitro has been reevaluated
      using this method. Together with our previous results (Nucleic Acids Res. 2002,
      30, 4470-4480) these experiments identify the essential residues in the alignment
      domain of human telomerase RNA that contribute to the activity and processivity
      of telomerase.

PMID- 16608334
TI  - Electronic and molecular structure of photoexcited [Ru(II)(bpy)3]2+ probed by
      picosecond X-ray absorption spectroscopy.
AB  - L(2,3) X-ray absorption spectra of aqueous [Ru(II)(bpy)3]2+ have been recorded in
      its ground and excited states, 50 ps after short pulse laser excitation.
      Significant changes in both the XANES (X-ray Near-Edge Absorption Structure) and
      the EXAFS (Extended X-ray Absorption Fine Structure) regions of the excited state
      complex are detected. The XANES line shapes have been quantitatively simulated
      using a crystal field multiplet code in trigonal symmetry. In addition, spectral
      changes in the EXAFS region of both ground and excited states are analyzed in
      order to extract structural parameters of their corresponding molecular
      structures. We obtain a Ru-N bond contraction by approximately 0.03 angstroms in
      the excited-state complex, as compared to the ground-state compound. This
      contraction results from electrostatic and polarization contributions, limited by
      steric constraints on the bpy ligands.

PMID- 16608335
TI  - Spectroscopic studies of the corrinoid/iron-sulfur protein from Moorella
      thermoacetica.
AB  - Methyl transfer reactions are important in a number of biochemical pathways. An
      important class of methyltransferases uses the cobalt cofactor cobalamin, which
      receives a methyl group from an appropriate methyl donor protein to form an
      intermediate organometallic methyl-Co bond that subsequently is cleaved by a
      methyl acceptor. Control of the axial ligation state of cobalamin influences both
      the mode (i.e., homolytic vs heterolytic) and the rate of Co-C bond cleavage.
      Here we have studied the axial ligation of a corrinoid iron-sulfur protein
      (CFeSP) that plays a key role in energy generation and cell carbon synthesis by
      anaerobic microbes, such as methanogenic archaea and acetogenic bacteria. This
      protein accepts a methyl group from methyltetrahydrofolate forming Me-Co(3+)CFeSP
      that then donates a methyl cation (Me) from Me-Co(3+)CFeSP to a nickel site on
      acetyl-CoA synthase. To unambiguously establish the binding scheme of the
      corrinoid cofactor in the CFeSP, we have combined resonance Raman, magnetic
      circular dichroism, and EPR spectroscopic methods with computational chemistry.
      Our results clearly demonstrate that the Me-Co3+ and Co2+ states of the CFeSP
      have an axial water ligand like the free MeCbi+ and Co(2+)Cbi+ cofactors;
      however, the Co-OH2 bond length is lengthened by about 0.2 angstroms for the
      protein-bound cofactor. Elongation of the Co-OH2 bond of the CFeSP-bound cofactor
      is proposed to make the cobalt center more "Co1+-like", a requirement to
      facilitate heterolytic Co-C bond cleavage.

PMID- 16608336
TI  - ENDOR of NO-ligated cytochrome c'.
AB  - The five-coordinate NO-bound heme in cytochrome c' from an overexpressing variant
      of denitrifying R. sphaeroides 2.4.3 was investigated by proton, nitrogen, and
      deuterium Q-band ENDOR (electron nuclear double resonance). ENDOR was a direct
      probe of the unpaired electron density on the nitrogen of NO and, as measured
      across the EPR line shape, showed a hyperfine coupling range from 36 to 44 MHz
      for 14NO and 51 to 63 MHz for 15NO. The smallest NO coupling occurred at an
      electronic g-tensor axis perpendicular to the FeNO plane, and the largest
      hyperfine coupling occurred in the FeNO plane where the highest nitrogen valence
      spin density is located. The isotropic component of the NO hyperfine coupling
      indicated that the electron spin on the NO is not simply in a pi orbital having
      only 2p character but is in an orbital having 2s and 2p character in a 1:2 ratio.
      ENDOR frequencies from heme meso-protons, assigned with reference to porphyrin
      models, were determined to result from an anisotropic hyperfine tensor. This
      tensor indicated the orientation of the heme with respect to the FeNO plane and
      showed that the FeNO plane bisects the heme N-Fe-N 90 degrees angle. ENDOR
      provided additional structural information through dipolar couplings, as follows:
      (1) to the nearest proton of the Phe14 ring, approximately 3.1 A away from the
      heme iron, where Phe14 is positioned to occlude binding of NO as a 6th (distal)
      ligand; (2) to exchangeable deuterons assigned to Arg127 which may H-bond with
      the proximal NO ligand.

PMID- 16608337
TI  - Aryl transfer between Pd(II) centers or Pd(IV) intermediates in Pd-catalyzed
      domino reactions.
AB  - A computational study has been performed to determine the mechanism of the key
      steps of Pd-catalyzed domino reactions in which C(sp2)-C(sp2) are formed from
      aryl and alkenyl halides. DFT calculations were done on model complexes of the
      proposed intermediates, with PH3 and H2O as ancillary ligands, to explore two
      possible mechanisms: the oxidative addition of aryl or alkenyl halides to
      palladacycles to give Pd(IV) intermediates, and the transmetalation-type reaction
      of aryl or alkenyl ligands between two Pd(II) centers, a palladacycle, and a
      Pd(II) complex formed by oxidative addition of aryl or alkenyl halides to Pd0. We
      have shown that oxidative addition of iodoethylene to Pd0 precursors is more
      favorable than oxidative addition to Pd(II) palladacycles, whereas
      transmetalation-type reactions between Pd(II) complexes are facile. Similar
      results were obtained with iodobenzene instead of iodoethylene and formamide as
      the ancillary ligand. These results suggest that Pd(IV) intermediates are not
      involved in these reactions.

PMID- 16608338
TI  - Microbead chemical switches: an approach to detection of reactive organophosphate
      chemical warfare agent vapors.
AB  - In this article, we describe the preparation and application of microbeads that
      exhibit a "turn on" fluorescence response within seconds of exposure to diethyl
      chlorophosphate (DCP) vapor. This sensing approach is modeled after the mechanism
      for acetylcholinesterase enzyme activity inhibition and uses a specific and
      irreversible reaction between phosphoryl halides and a fluorescent indicator. The
      microbeads are fabricated by adsorbing fluoresceinamine (FLA) onto carboxylate
      functionalized polymer microbeads coated with poly(2-vinylpyridine) (PVP). When
      the microbeads are subjected to DCP vapor, the conversion of FLA into a
      phosphoramide causes a rapid and intense fluorescence increase. The PVP layer
      provides a high density of proton-accepting pyridine nitrogen sites that
      neutralize the HCl released during the reaction, thereby maintaining high product
      fluorescence, even after vapor exposure. No significant response is observed when
      the microbeads are subjected to other nerve agent simulants, a mustard gas
      simulant, and volatile organics. The size, sensitivity, and subsecond response of
      these microbeads make them suitable for nerve agent vapor detection and inclusion
      into microbead sensor arrays.

PMID- 16608339
TI  - Transition states for glucopyranose interconversion.
AB  - Glucose is a central molecule in biology and chemistry, and the anomerization
      reaction has been studied for more than 150 years. Transition-state structure is
      the last impediment to an in-depth understanding of its solution chemistry. We
      have measured kinetic isotope effects on the rate constants for approach of alpha
      glucopyranose to its equilibrium with beta-glucopyranose, and these were
      converted into unidirectional kinetic isotope effects using equilibrium isotope
      effects. Saturation transfer 13C NMR spectroscopy has yielded the relative free
      energies of the transition states for the ring-opening and ring-closing
      reactions, and both transition states contribute to the experimental kinetic
      isotope effects. Both transition states of the anomerization process have been
      modeled with high-level computational theory with constraints from the primary,
      secondary, and solvent kinetic isotope effects. We have found the transition
      states for anomerization, and we have also concluded that it is forbidden for the
      water molecule to form a hydrogen bond bridge to both OH1 and O5 of glucose
      simultaneously in either transition state.

PMID- 16608340
TI  - The 5-deoxy-5-methylthio-xylofuranose residue in mycobacterial lipoarabinomannan.
      absolute stereochemistry, linkage position, conformation, and immunomodulatory
      activity.
AB  - Mycobacteria produce a cell-surface glycoconjugate, lipoarabinomannan (LAM),
      which has been shown to be a potent modulator of the immune response that arises
      from infection by these organisms. Recently, LAM from the human pathogens
      Mycobacterium tuberculosis and M. kansasii has been shown to contain an unusual 5
      deoxy-5-methylthio-xylofuranose (MTX) residue as well as its corresponding
      oxidized counterpart, 5-deoxy-5-methylsulfoxy-xylofuranose (MSX). To date, the
      absolute configuration of these residues and their linkage position to the
      polysaccharide are unknown, as is their biological role. Through the combined use
      of chemical synthesis and NMR spectroscopy, we have established that the MTX/MSX
      residues in these glycoconjugates are of the d-configuration and that they are
      linked alpha-(1-->4) to a mannopyranose residue in the mannan portion of the
      glycan. Conformational analysis of the MTX/MSX residue using NMR spectroscopy
      showed differences in ring conformation and as well as in the rotamer populations
      about the C-4-C-5 bond, as compared to the parent compound, methyl alpha-d
      xylofuranoside. Two of the synthesized disaccharides, 3 and 34, were tested in
      cytokine induction assays, and neither led to the production of TNF-alpha or IL
      12p70. In contrast, both demonstrated modest inhibitory properties when these
      same cytokines were induced using a preparation of Interferon-gamma and
      Staphylococcus aureus Cowan strain (SAC/IFN-gamma). These latter observations
      suggest that this motif may play a role in the immune response arising from
      mycobacterial infection.

PMID- 16608341
TI  - Probing methyl dynamics from 13C autocorrelated and cross-correlated relaxation.
AB  - An understanding of side-chain motions in protein is of great interest since side
      chains often play an important role in protein folding and intermolecular
      interactions. A novel method for measuring dipole-dipole cross-correlated
      relaxation in methyl groups of uniformly 13C-labeled proteins without deuteration
      has been developed by our group. The excellent agreement between dynamic
      parameters of methyl groups in ubiquitin obtained from the cross-correlated
      relaxation and 13C spin-lattice relaxation and those derived previously from 2H
      relaxation data demonstrates the reliability of the method. This method was
      applied to the study of side-chain dynamics of human intestinal fatty acid
      binding protein (IFABP) with and without its ligand. Binding of oleic acid to the
      protein results in decreased mobility of most of the methyl groups in the binding
      region, whereas no significant change in mobility was observed for methyl groups
      in the nonbinding region.

PMID- 16608342
TI  - Dynamics of low temperature induced water shedding from AOT reverse micelles.
AB  - The effects of low temperature and ionic strength on water encapsulated within
      reverse micelles were investigated by solution NMR. Reverse micelles composed of
      AOT and pentane and solutions with varying concentrations of NaCl were studied at
      temperatures ranging from 20 degrees C to -30 degrees C. One-dimensional (1)H
      solution NMR spectroscopy was used to monitor the quantity and structure of
      encapsulated water. At low temperatures, e.g., -30 degrees C, reverse micelles
      lose water at rates that are dependent on the ionic strength of the aqueous
      nanopool. The final water loading (w0 = [water]/[surfactant]) of the reverse
      micelles is likewise dependent on the ionic strength of the aqueous phase.
      Remarkably, water resonance(s) at temperatures between -20 degrees C and -30
      degrees C displayed fine structure indicating the presence of multiple transient
      water populations. Results of this study demonstrate that reverse micelles are an
      excellent vehicle for studies of confined water across a broad range of
      conditions, including the temperature range that provides access to the
      supercooled state.

PMID- 16608343
TI  - Synthesis of an anionically chargeable, high-molar-mass, second-generation
      dendronized polymer and the observation of branching by scanning force
      microscopy.
AB  - An efficient synthesis of a methacrylate-based, second-generation (G2)
      dendronized macromonomer and its free radical polymerization to the corresponding
      high-molar-mass G2 dendronized polymer are described. The molar mass is
      determined by gel permeation chromatography (GPC), light-scattering, and
      analytical ultracentrifugation and compared with values estimated from a scanning
      force microscopy (SFM) contour lengths analysis of individualized polymer strands
      on mica. The polymer carries terminal tert-butyl-protected carboxyl groups, the
      degree of deprotection of which with trifluoroacetic acid is quantified by NMR
      spectroscopy using the highest molar mass sample. SFM imaging of both protected
      (noncharged) and unprotected (charged) dendronized polymers on solid substrates
      reveals mostly linear chains but also some with main-chain branches. The nature
      of these branches is investigated and the degree roughly estimated to which they
      are formed. Finally, a synthetic model experiment is described which sheds some
      light on the aspect of whether chain transfer, a process that could lead to
      covalent branching, is of importance in the synthesis of the present dendronized
      polymers.

PMID- 16608344
TI  - Aluminacyclopropene: syntheses, characterization, and reactivity toward terminal
      alkynes.
AB  - Reactions of LAl with ethyne, mono- and disubstituted alkynes, and diyne to
      aluminacyclopropene LAl[eta2-C2(R1)(R2)] ((L = HC[(CMe)(NAr)]2, Ar = 2,6
      iPr2C6H3); R1 = R2 = H, (1); R1 = H, R2 = Ph, (2); R1 = R2 = Me, (3); R1 = SiMe3,
      R2 = C[triple bond]CSiMe3, (4)) are reported. Compounds 1 and 2 were obtained in
      equimolar quantities of the starting materials at low temperature. The amount of
      C2H2 was controlled by removing an excess of C2H2 in the range from -78 to -50
      degrees C. Compound 4 can be alternatively prepared by the substitution reaction
      of LAl[eta2-C2(SiMe3)2] with Me3SiC[triple bond]CC[triple bond]CSiMe3 or by the
      reductive coupling reaction of LAlI2 with potassium in the presence of
      Me3SiC[triple bond]CC[triple bond]CSiMe3. The reaction of LAl with excess C2H2
      and PhC[triple bond]CH (<1:2) afforded the respective alkenylalkynylaluminum
      compounds LAl(CH=CH2)(C[triple bond]CH) (5) and LAl(CH=CHPh)(C[triple bond]CPh)
      (6). The reaction of LAl(eta2-C2Ph2) with C2H2 and PhC[triple bond]CH yielded
      LAl(CPh=CHPh)(C[triple bond]CH) (7) and LAl(CPh=CHPh)(C[triple bond]CPh) (8),
      respectively. Rationally, the formation of 5 (or 6) may proceed through the
      corresponding precursor 1 (or 2). The theoretical studies based on DFT
      calculations show that an interaction between the Al(I) center and the C[triple
      bond]C unit needs almost no activation energy. Within the AlC2 ring the
      computational Al-C bond order of ca. 1 suggests an Al-C sigma bond and therefore
      less pi electron delocalization over the AlC2 ring. The computed Al-eta2-C2 bond
      dissociation energies (155-82.6 kJ/mol) indicate a remarkable reactivity of
      aluminacyclopropene species. Finally, the 1H NMR spectroscopy monitored reaction
      of LAl(eta2-C2Ph2) and PhC[triple bond]CH in toluene-d8 may reveal an acetylenic
      hydrogen migration process.

PMID- 16608345
TI  - A biohybrid dynamic random access memory.
AB  - We report that GABA(A) receptors in a patch-clamped biological cell form a short
      term memory circuit when integrated with a scanning-probe microfluidic device.
      Laminar patterns of receptor activators (agonists) provided by the microfluidic
      device define and periodically update the data input which is read and stored by
      the receptors as state distributions (based on intrinsic multistate kinetics).
      The memory is discharged over time and lasts for seconds to minutes depending on
      the input function. The function of the memory can be represented by an
      equivalent electronic circuit with striking similarity in function to a dynamic
      random access memory (DRAM) used in electronic computers. Multiplexed biohybrid
      memories may form the basis of large-scale integrated biocomputational/sensor
      devices with the curious ability to use chemical signals including odorants,
      neurotransmitters, chemical and biological warfare agents, and many more as input
      signals.

PMID- 16608346
TI  - Selective interaction of large or charge-transfer aromatic molecules with
      metallic single-wall carbon nanotubes: critical role of the molecular size and
      orientation.
AB  - Using first principles calculations, we report for the first time that large
      nearly neutral aromatic molecules, such as naphthalene and anthracene, and small
      charge-transfer aromatic molecules, such as TCNQ and DDQ, interact more strongly
      with metallic single-wall carbon nanotubes (SWNTs) versus their semiconducting
      counterparts as the molecular orientation of DDQ is taken into account. Hence two
      new mechanisms for separating metallic and semiconducting SWNTs via noncovalent
      pi-pi stacking or charge-transfer interaction are suggested.

PMID- 16608347
TI  - The structure of liquid tetrahydrofuran.
AB  - Hydrogen/deuterium isotopic substitution neutron diffraction techniques have been
      used to measure the structural correlation functions of liquid tetrahydrofuran at
      room temperature. Empirical potential structure refinement (EPSR) has been used
      to build a three-dimensional model of the liquid structure that is consistent
      with the experimental data. Analysis to the level of the orientational
      correlation functions shows that the liquid displays a preference for T-like
      configurations between the tetrahydrofuran molecules, a local structure that
      results in void-like regions of approximately 1.25 angstroms radius within the
      bulk liquid. The surface chemistry of these voids suggests a slightly positive
      electrostatic character. These findings are consistent with the known propensity
      of the liquid to solvate free electrons.

PMID- 16608348
TI  - Fine tuning of the rotary motion by structural modification in light-driven
      unidirectional molecular motors.
AB  - The introduction of bulky substituents at the stereogenic center of light-driven
      second-generation molecular motors results in an acceleration of the speed of
      rotation. This is due to a more strained structure with elongated C=C bonds and a
      higher energy level of the ground state relative to the transition state for the
      rate-limiting thermal isomerization step. Understanding the profound influence
      that variation of the substituent at the stereogenic center holds over the
      rotational speed of the light-driven molecular motor has enabled the development
      of the fastest molecular motor reported thus far.

PMID- 16608349
TI  - Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex
      with the 20S proteasome reveal important consequences of beta-lactone ring
      opening and a mechanism for irreversible binding.
AB  - The crystal structures of the yeast 20S proteasome core particle (CP) in complex
      with Salinosporamides A (NPI-0052; 1) and B (4) were solved at <3 angstroms
      resolution. Each ligand is covalently bound to Thr1O(gamma) via an ester linkage
      to the carbonyl derived from the beta-lactone ring of the inhibitor. In the case
      of 1, nucleophilic addition to the beta-lactone ring is followed by addition of C
      3O to the chloroethyl group, giving rise to a cyclic ether. The crystal
      structures were compared to that of the omuralide/CP structure solved previously,
      and the collective data provide new insights into the mechanism of inhibition and
      irreversible binding of 1. Upon opening of the beta-lactone ring, C-3O assumes
      the position occupied by a water molecule in the unligated enzyme and hinders
      deacylation of the enzyme-ligand complex. Furthermore, the resulting protonation
      state of Thr1NH2 deactivates the catalytic N-terminus.

PMID- 16608350
TI  - Simulating FRET from tryptophan: is the rotamer model correct?
AB  - We present a computational model study designed to simulate the results of time
      resolved fluorescence spectra of tryptophan in proteins. In such measurements,
      the occurrence of more than one fluorescence lifetime is generally attributed to
      the existence of several tryptophan rotamers and/or structural conformations of
      the protein structure. The protein system we chose for this initial study is the
      tetracycline repressor (TetR), an interesting model system for the investigation
      of the mechanisms of transcriptional regulation. Fluorescence resonance energy
      transfer (FRET) from tryptophan to tetracycline is frequently observed in
      complexes of the TetR with the antibiotic tetracycline. We use a combined
      classical/quantum mechanical approach to model the structure and the
      spectroscopic properties of the TetR-tetracycline complex. A classical molecular
      dynamics simulation provides input geometries for semiempirical quantum
      mechanical/molecular mechanical (QM/MM) single-point configuration interaction
      (CI) calculations, which are used to calculate tryptophan vertical absorption and
      fluorescence energies and intensities as well as relative FRET rate constants.
      These rate constants together with the Einstein coefficients for spontaneous
      emission and an assumed rate for nonradiative deactivation allow us to simulate
      fluorescence decay curves with and without FRET and for the entire ensemble as
      well as for individual rotamers. Our results indicate that the classical "rotamer
      model", used to explain the multiexponential fluorescence-decay curves of time
      resolved tryptophan emission spectra, can be extended to systems with FRET
      acceptors present in the protein matrix but that the interpretation of the fitted
      lifetimes is different to that usually used.

PMID- 16608351
TI  - Enantioselective synthesis of cyclic enol ethers and all-carbon quaternary
      stereogenic centers through catalytic asymmetric ring-closing metathesis.
AB  - The first examples of catalytic asymmetric ring-closing metathesis (ARCM)
      reactions of enol ethers are reported. To identify the most effective catalysts,
      various chiral Mo- and Ru-based catalysts were screened. Although chiral Ru
      catalysts (those that do not bear a phosphine ligand) promote ARCM in some cases,
      such transformations proceed in <10% ee. In contrast, Mo-based alkylidenes give
      rise to efficient ARCM and deliver the desired products in the optically enriched
      form. Thus, Mo-catalyzed enantioselective transformations allow access to various
      five- and six-membered cyclic enol ethers in up to 94% ee from readily available
      achiral starting materials. The first examples of catalytic ARCM that lead to the
      formation of all-carbon quaternary stereogenic centers are also disclosed.
      Mechanistic models that offer a plausible rationale for the identity of major
      enantiomers as well as the observed levels of enantioselectivity are provided.
      Representative examples demonstrate that the enol ether moiety and the unreacted
      alkene of the ARCM products can be discriminated with excellent site selectivity
      (>98%).

PMID- 16608352
TI  - Theoretical study on tertiary structural elements of beta-peptides: nanotubes
      formed from parallel-sheet-derived assemblies of beta-peptides.
AB  - Parallel or polar strands of beta-peptides spontaneously form nanotubes of
      different sizes in a vacuum as determined by ab initio calculations. Stability
      and conformational features of [CH3CO-(beta-Ala)k-NHCH3]l (1 < or = k < or = 4, 2
      < or = l < or = 4) models were computed at different levels of theory (e.g.,
      B3LYP/6-311++G(d,p)// B3LYP/6-31G(d), with consideration of BSSE). For the first
      time, calculations demonstrate that sheets of beta-peptides display nanotubular
      characteristics rather than two-dimensional extended beta-layers, as is the case
      of alpha-peptides. Of the configurations studied, k = l = 4 gave the most stable
      nanotubular structure, but larger assemblies are expected to produce even more
      stable nanotubes. As with other nanosystems such as cyclodextrane, these
      nanotubes can also incorporate small molecules, creating a diverse range of
      applications for these flexible, biocompatible, and highly stable molecules. The
      various side chains of beta-peptides can make these nanosystems rather versatile.
      Energetic and structural features of these tubular model systems are detailed in
      this paper. It is hoped that the results presented in this paper will stimulate
      experimental research in the field of nanostructure technology involving beta
      peptides.

PMID- 16608353
TI  - Role of topology, nonadditivity, and water-mediated interactions in predicting
      the structures of alpha/beta proteins.
AB  - The folding of alpha/beta proteins involves most of the commonly known structural
      and dynamic complexities of the protein energy landscapes. Thus, the interplay
      among different structural components, taking into account the cooperative
      interactions, is important in determining the success of protein structure
      prediction. In this work we present further developments of our knowledge-based
      force field for alpha/beta proteins, introducing more realistic modeling of many
      body interactions governing the folding of beta-sheets. The model's innovations
      highlight both specific topological characteristics of secondary structures and
      the generic nonadditive interactions that are mediated by water. We also
      investigate how a coarse biasing of the protein morphology can be used to
      understand the role of heterogeneity in protein collapse. Analysis of the
      simulation results for three test alpha/beta proteins indicates that the addition
      of the topological and many-body ingredients to the model helps to greatly reduce
      the roughness in the energy landscape. Consequently, high quality candidate
      structures for alpha/beta proteins can be generated from simulated annealing
      runs, using very modest amounts of computer time.

PMID- 16608354
TI  - Mechanism of Al(III)-catalyzed transamidation of unactivated secondary
      carboxamides.
AB  - The carbon-nitrogen bond of secondary carboxamides is generally thermodynamically
      and kinetically unreactive; however, we recently discovered that the
      trisamidoaluminum(III) dimer Al2(NMe2)6 catalyzes facile transamidation between
      simple secondary carboxamides and primary amines under moderate conditions. The
      present report describes kinetic and spectroscopic studies that illuminate the
      mechanism of this unusual transformation. The catalytic reaction exhibits a
      bimolecular rate law with a first-order dependence on the Al(III) and amine
      concentrations. No rate dependence on the carboxamide concentration is observed.
      Spectroscopic studies (1H and 13C NMR, FTIR) support a catalyst resting state
      that consists of a mixture of tris-(kappa2-amidate)aluminum(III) complexes. These
      results, together with the presence of a significant kinetic isotope effect when
      deuterated amine substrate (RND2) is used, implicate a mechanism in which the
      amine undergoes preequilibrium coordination to aluminum and proton transfer to a
      kappa2-amidate ligand to yield an Al(kappa2-amidate)2(kappa1-carboxamide)(NHR)
      complex, followed by rate-limiting intramolecular delivery of the amido ligand
      (NHR) to the neutral Al(III)-activated kappa1-carboxamide. Noteworthy in this
      mechanism is the bifunctional character of Al(III), which is capable of
      activating both the amine nucleophile and the carboxamide electrophile in the
      reaction.

PMID- 16608355
TI  - Fluorescent signal amplification of carbocyanine dyes using engineered viral
      nanoparticles.
AB  - We report enhancement in the fluorescent signal of the carbocyanine dye Cy5 by
      using an engineered virus as a scaffold to attach >40 Cy5 reporter molecules at
      fixed locations on the viral capsid. Although cyanine dye loading is often
      accompanied by fluorescence quenching, our results demonstrate that organized
      spatial distribution of Cy5 reporter molecules on the capsid obviates this
      commonly encountered problem. In addition, we observe energy transfer from the
      virus to adducted dye molecules, resulting in a highly fluorescent viral
      nanoparticle. We have used this enhanced fluorescence for the detection of DNA
      DNA hybridization. When compared with the most often used detection methods in a
      microarray-based genotyping assay for Vibrio cholerae O139, these viral
      nanoparticles markedly increased assay sensitivity, thus demonstrating their
      applicability for existing DNA microarray protocols.

PMID- 16608356
TI  - 51V solid-state magic angle spinning NMR spectroscopy of vanadium
      chloroperoxidase.
AB  - We report 51V solid-state NMR spectroscopy of the 67.5-kDa vanadium
      chloroperoxidase, at 14.1 T. We demonstrate that, despite the low concentration
      of vanadium sites in the protein (one per molecule, 1 mumol of vanadium spins in
      the entire sample), the spinning sideband manifold spanning the central and the
      satellite transitions is readily detectable. The quadrupolar and chemical shift
      anisotropy tensors have been determined by numerical simulations of the spinning
      sideband envelopes and the line shapes of the individual spinning sidebands
      corresponding to the central transition. The observed quadrupolar coupling
      constant C(Q) of 10.5 +/- 1.5 MHz and chemical shift anisotropy delta(sigma) of 
      520 +/- 13 ppm are sensitive reporters of the geometric and electronic structure
      of the vanadium center. Density functional theory calculations of the NMR
      spectroscopic observables for an extensive series of active site models indicate
      that the vanadate cofactor is most likely anionic with one axial hydroxo- group
      and an equatorial plane consisting of one hydroxo- and two oxo- groups. The work
      reported in this manuscript is the first example of 51V solid-state NMR
      spectroscopy applied to probe the vanadium center in a protein directly. This
      approach yields the detailed coordination environment of the metal unavailable
      from other experimental measurements and is expected to be generally applicable
      for studies of diamagnetic vanadium sites in metalloproteins.

PMID- 16608357
TI  - Changing the ligation of the distal [4Fe4S] cluster in NiFe hydrogenase impairs
      inter- and intramolecular electron transfers.
AB  - In NiFe hydrogenases, electrons are transferred from the active site to the redox
      partner via a chain of three Iron-Sulfur clusters, and the surface-exposed
      [4Fe4S] cluster has an unusual His(Cys)3 ligation. When this Histidine (H184 in
      Desulfovibrio fructosovorans) is changed into a cysteine or a glycine, a distal
      cubane is still assembled but the oxidative activity of the mutants is only 1.5
      and 3% of that of the WT, respectively. We compared the activities of the WT and
      engineered enzymes for H2 oxidation, H+ reduction and H/D exchange, under various
      conditions: (i) either with the enzyme directly adsorbed onto an electrode or
      using soluble redox partners, and (ii) in the presence of exogenous ligands whose
      binding to the exposed Fe of H184G was expected to modulate the properties of the
      distal cluster. Protein film voltammetry proved particularly useful to unravel
      the effects of the mutations on inter and intramolecular electron transfer (ET).
      We demonstrate that changing the coordination of the distal cluster has no effect
      on cluster assembly, protein stability, active-site chemistry and proton
      transfer; however, it slows down the first-order rates of ET to and from the
      cluster. All-sulfur coordination is actually detrimental to ET, and
      intramolecular (uphill) ET is rate determining in the glycine variant. This
      demonstrates that although [4Fe4S] clusters are robust chemical constructs, the
      direct protein ligands play an essential role in imparting their ability to
      transfer electrons.

PMID- 16608358
TI  - Synthesis, structure, and reactivity of 13-vertex carboranes and 14-vertex
      metallacarboranes.
AB  - Syntheses, properties, and synthetic applications of 13-vertex closo- and nido
      carboranes are reported. Reactions of the nido-carborane salt [(CH2)3C2B10H10]Na2
      with dihaloborane reagents afforded 13-vertex closo-carboranes 1,2-(CH2)3-3-R-1,2
      C2B11H10 (R = H (2), Ph (3), Z-EtCH=C(Et) (4), E-(t)BuCH=CH (5)). Treatment of
      the arachno-carborane salt [(CH2)3C2B10H10]Li4 with HBBr2.SMe2 gave both the 13
      vertex carborane 2 and a 14-vertex closo-carborane (CH2)3C2B12H12 (8). On the
      other hand, the reaction of [C6H4(CH2)2C2B10H10]Li4 with HBBr2.SMe2 generated
      only a 13-vertex closo-carborane 1,2-C6H4(CH2)2-1,2-C2B11H11 (9). Electrophilic
      substitution reactions of 2 with excess MeI, Br2, or I2 in the presence of a
      catalytic amount of AlCl3 produced the hexa-substituted 13-vertex carboranes
      8,9,10,11,12,13-X6-1,2-(CH2)3-1,2-C2B11H5 (X = Me (10), Br (11), I (12)). The
      halogenated products 11 and 12 displayed unexpected instability toward moisture.
      The 13-vertex closo-carboranes were readily reduced by groups 1 and 2 metals.
      Accordingly, several 13-vertex nido-carborane dianionic salts [nido-1,2-(CH2)3
      1,2-C2B11H11][Li2(DME)2(THF)2] (13), [[nido-1,2-(CH2)3-1,2-C2B11H11][Na2(THF)4]]n
      (13a), [[nido-1,2-(CH2)3-3-Ph-1,2-C2B11H10][Na2(THF)4]]n (14), [[nido-1,2
      C6H4(CH2)2-1,2-C2B11H11][Na2(THF)4]]n (15), and [nido-1,2-(CH2)3-1,2
      C2B11H11][M(THF)5] (M = Mg (16), Ca (17)) were prepared in good yields. These
      carbon-atom-adjacent nido-carboranes were not further reduced to the
      corresponding arachno species by lithium metal. On the other hand, like other
      nido-carborane dianions, they were useful synthons for the production of super
      carboranes and supra-icosahedral metallacarboranes. Interactions of 13a with
      HBBr2.SMe2, (dppe)NiCl2, and (dppen)NiCl2 gave the 14-vertex carborane 8 and
      nickelacarboranes [eta5-(CH2)3C2B11H11]Ni(dppe) (18) and [eta5
      (CH2)3C2B11H11]Ni(dppen) (19), respectively. All complexes were fully
      characterized by various spectroscopic techniques and elemental analyses. Some
      were further confirmed by single-crystal X-ray diffraction studies.

PMID- 16608359
TI  - Molecular self-assembly at bare semiconductor surfaces: preparation and
      characterization of highly organized octadecanethiolate monolayers on GaAs(001).
AB  - Through rigorous control of preparation conditions, organized monolayers with a
      highly reproducible structure can be formed by solution self-assembly of
      octadecanethiol on GaAs (001) at ambient temperature. A combination of
      characterization probes reveal a structure with conformationally ordered alkyl
      chains tilted on average at 14 +/- 1 degrees from the surface normal with a 43 +/
      5 degrees twist, a highly oleophobic and hydrophobic ambient surface, and direct
      S-GaAs attachment. Analysis of the tilt angle and film thickness data shows a
      significant mismatch of the average adsorbate molecule spacings with the spacings
      of an intrinsic GaAs(001) surface lattice. The monolayers are stable up to
      approximately 100 degrees C and exhibit an overall thermal stability which is
      lower than that of the same monolayers on Au[111] surfaces. A two-step solution
      assembly process is observed: rapid adsorption of molecules over the first
      several hours to form disordered structures with molecules lying close to the
      substrate surface, followed by a slow densification and asymptotic approach to
      final ordering. This process, while similar to the assembly of alkanethiols on
      Au[111], is nearly 2 orders of magnitude slower. Finally, despite differences in
      assembly rates and the thermal stability, exchange experiments with isotopically
      tagged molecules show that the octadecanethiol on GaAs(001) monolayers undergo
      exchange with solute thiol molecules at roughly the same rate as the
      corresponding exchanges of the same monolayers on Au[111].

PMID- 16608360
TI  - Solution synthesis of germanium nanowires using a Ge2+ alkoxide precursor.
AB  - A simple solution synthesis of germanium (Ge0) nanowires under mild conditions
      (<400 degrees C and 1 atm) was demonstrated using germanium 2,6-dibutylphenoxide,
      Ge(DBP)2 (1), as the precursor where DBP = 2,6-OC6H3(C(CH3)3)2. Compound 1,
      synthesized from Ge(NR2)2 where R = SiMe3 and 2 equiv of DBP-H, was characterized
      as a mononuclear species by single-crystal X-ray diffraction. Dissolution of 1 in
      oleylamine, followed by rapid injection into a 1-octadecene solution heated to
      300 degrees C under an atmosphere of Ar, led to the formation of Ge0 nanowires.
      The Ge0 nanowires were characterized by transmission electron microscopy (TEM), X
      ray diffraction analysis, and Fourier transform infrared spectroscopy. These
      characterizations revealed that the nanowires are single crystalline in the cubic
      phase and coated with oleylamine surfactant. We also observed that the nanowire
      length (0.1-10 microm) increases with increasing temperature (285-315 degrees C)
      and time (5-60 min). Two growth mechanisms are proposed based on the TEM images
      intermittently taken during the growth process as a function of time: (1) self
      seeding mechanism where one of two overlapping nanowires serves as a seed, while
      the other continues to grow as a wire; and (2) self-assembly mechanism where an
      aggregate of small rods (<50 nm in diameter) recrystallizes on the tip of a
      longer wire, extending its length.

PMID- 16608361
TI  - Synthesis and biochemical evaluation of phosphonoformate
      oligodeoxyribonucleotides.
AB  - Phosphonoformate oligodeoxyribonucleotides were prepared via a solid phase
      synthesis strategy. The first step in the preparation of appropriate synthons was
      condensation of bis(N,N-diisopropylamino)phosphine and diphenylmethylsilylethyl
      chloroformate in the presence of sodium metal to yield formic acid, [bis(N,N
      diisopropylamino)phosphino]-beta-(diphenylmethylsilylethyl) ester. The product of
      this reaction was then condensed with appropriately protected 2'-deoxynucleosides
      using 4,5-dicyanoimidazole to yield the 3'-O-phosphinoamidite reactive monomers.
      The exocyclic amines of cytosine, adenine, and guanine were protected with 9
      fluorenylmethyloxycarbonyl, and oligodeoxyribonucleotides were synthesized on
      controlled pore glass using the hydroquinone-O,O'-diacetic acid linker. Synthons
      were sequentially added to this support using tetrazole as an activator, oxidized
      to phosphonoformate, and the transient 5'-protecting group was removed with acid.
      Following total synthesis of an oligomer, protecting groups were removed with
      TEMED.HF and products purified by HPLC. These analogues were resistant to
      nucleases, formed duplexes with complementary RNA (A-form), and, as chimeric
      oligomers containing phosphate at selected sites, stimulated RNase H1 activity.

PMID- 16608363
TI  - Triple-ion interactions for the construction of supramolecular capsules.
AB  - A novel type of [2+4] capsules based on triple-ion interactions was obtained.
      Four monovalent anions (bromide, nitrate, acetate, and tosylate) bring together
      two tetrakis(pyridiniummethyl)tetramethyl cavitands by pyridinium-anion
      pyridinium interactions. ESI-MS experiments have confirmed the capsule structure
      due to different fragmentation pathways of triple ions, cations, and ion-pairs.
      Each capsule encapsulates one or two anions, depending on its size. The capsules
      exist in equilibrium with hemicapsules containing three walls. The latter form
      complexes with phenols and anilines to give new unsymmetrical capsules containing
      both pyridinium-anion-pyridinium and pyridinium-guest-pyridinium walls.

PMID- 16608362
TI  - Probing the transition state ensemble of a protein folding reaction by pressure
      dependent NMR relaxation dispersion.
AB  - The F61A/A90G mutant of a redesigned form of apocytochrome b562 folds by an
      apparent two-state mechanism. We have used the pressure dependence of 15N NMR
      relaxation dispersion rate profiles to study the changes in volumetric parameters
      that accompany the folding reaction of this protein at 45 degrees C. The
      experiments were performed under conditions where the folding/unfolding
      equilibrium could be studied at each pressure without addition of denaturants.
      The exquisite sensitivity of the methodology to small changes in
      folding/unfolding rates facilitated the use of relatively low-pressure values
      (between 1 and 270 bar) so that pressure-induced changes to the unfolded state
      ensemble could be minimized. A volume change for unfolding of -81 mL/mol is
      measured (at 1 bar), a factor of 1.4 larger (in absolute value) than the volume
      difference between the transition state ensemble (TSE) and the unfolded state.
      Notably, the changes in the free energy difference between folded and unfolded
      states and in the activation free energy for folding were not linear with
      pressure. Thus, the difference in the isothermal compressibility upon unfolding (
      0.11 mL mol(-1) bar(-1)) and, for the first time, the compressibility of the TSE
      relative to the unfolded state (0.15 mL mol(-1) bar(-1)) could be calculated. The
      results argue for a TSE that is collapsed but loosely packed relative to the
      folded state and significantly hydrated, suggesting that the release of water
      occurs after the rate-limiting step in protein folding. The notion of a collapsed
      and hydrated TSE is consistent with expectations based on earlier temperature
      dependent folding studies, showing that the barrier to folding at 45 degrees C is
      entropic (Choy, W. Y.; Zhou, Z.; Bai, Y.; Kay, L. E. J. Am. Chem. Soc. 2005, 127,
      5066-5072).

PMID- 16608364
TI  - Metal supported on dendronized magnetic nanoparticles: highly selective
      hydroformylation catalysts.
AB  - A method for homogenizing heterogeneous catalyst is described. The method is
      based on growing polyaminoamido (PAMAM) dendrons on silica-coated magnetic
      nanoparticles. After the dendronizing process, the silica-coated magnetic
      nanoparticles are more stable and more soluble in organic solvents. The
      dendronized particles are phosphonated, complexed with [Rh(COD)Cl]2, and applied
      in catalytic hydroformylation reactions. These new catalysts are proven to be
      highly selective and reactive.

PMID- 16608365
TI  - A new photostable terrylene diimide dye for applications in single molecule
      studies and membrane labeling.
AB  - A new terrylene diimide-based dye (WS-TDI) that is soluble in water has been
      synthesized, and its photophysical properties are characterized. WS-TDI forms
      nonfluorescing H-aggregates in water that show absorption bands being blue
      shifted with respect to those of the fluorescing monomeric form. The ratio of
      monomeric WS-TDI to aggregated WS-TDI was determined to be 1 in 14 400 from
      fluorescence correlation spectroscopy (FCS) measurements, suggesting the presence
      of a large amount of soluble, nonfluorescent aggregates in water. The presence of
      a surfactant such as Pluronic P123 or CTAB leads to the disruption of the
      aggregates due to the formation of monomers in micelles. This is accompanied by a
      strong increase in fluorescence. A single molecule study of WS-TDI in polymeric
      films of PVA and PMMA reveals excellent photostability with respect to
      photobleaching, far above the photostability of other common water-soluble dyes,
      such as oxazine-1, sulforhodamine-B, and a water-soluble perylenediimide
      derivative. Furthermore, labeling of a single protein such as avidin is
      demonstrated by FCS and single molecule photostability measurements. The high
      tendency of WS-TDI to form nonfluorescent aggregates in water in connection with
      its high affinity to lipophilic environments is used for the fluorescence
      labeling of lipid membranes and membrane containing compartments such as
      artificial liposomes or endosomes in living HeLa cells. The superior fluorescence
      imaging quality of WS-TDI in such applications is demonstrated in comparison to
      other well-known membrane staining dyes such as Alexa647 conjugated with dextran
      and FM 4-64 lipophilic styryl dye.

PMID- 16608366
TI  - Evolution of a total synthesis of (-)-kendomycin exploiting a Petasis-Ferrier
      rearrangement/ring-closing olefin metathesis strategy.
AB  - A convergent stereocontrolled total synthesis of (-)-kendomycin (1) has been
      achieved. The synthesis proceeds with a longest linear sequence of 21 steps,
      beginning with commercially available 2,4-dimethoxy-3-methylbenzaldehyde (12).
      Highlights of the synthesis include an effective Petasis-Ferrier
      union/rearrangement tactic to construct the sterically encumbered tetrahydropyran
      ring, a ring-closing metathesis to generate the C(4a-13-20a) macrocycle, an
      effective epoxidation/deoxygenation sequence to isomerize the C(13,14) olefin,
      and a biomimetic quinone-methide-lactol assembly to complete the synthesis.

PMID- 16608370
TI  - Systemic and localized scleroderma in children: current and future treatment
      options.
AB  - Scleroderma is a group of rare and complex diseases with varied clinical
      manifestations. The most obvious manifestation of the diseases is skin hardening
      and sclerosis. Scleroderma can be divided into two main subgroups: systemic and
      localized. The systemic form, also known as systemic sclerosis, involves diffuse
      skin involvement and potentially severe visceral involvement. Localized
      scleroderma on the other hand is more common in children and usually confined to
      a specific region of the body with no internal organ involvement. The juvenile
      forms of systemic sclerosis and localized scleroderma are important conditions in
      children because of the clinical severity and substantial mortality of systemic
      scleroderma and the major growth defects associated with childhood-onset
      localized disease even if the active disease itself is self-limited. The
      pathogenic pathways of the various forms of scleroderma are only partially
      defined, but the main defect in scleroderma is abnormal collagen deposition
      leading to eventual fibrosis in the skin as well as multiple organ systems such
      as the heart and lungs in juvenile systemic sclerosis. Therapeutics are divided
      into three main subgroups for systemic sclerosis: antifibrotics, anti
      inflammatories, and vasodilators. For localized disease, anti-inflammatories,
      vitamin D analogs, and UV irradiation have been investigated. However, the
      infrequency of scleroderma in the pediatric population plus the fact that this
      disease is very often self-limiting makes randomized controlled trials very
      difficult. It is for this reason that most data on treatment modalities for this
      disease have been extrapolated from studies in adult patients. There is no one
      therapy for systemic sclerosis or localized scleroderma that has proven to be
      very effective or significantly disease modifying. However, current therapeutic
      strategies must be initiated early in the disease course for maximum beneficial
      clinical effects. New interventions such as autologous stem cell transplant and
      cytokine-directed therapies are under investigation as potential treatments for
      this complex disease.

PMID- 16608369
TI  - Surviving childhood cancer: the impact on life.
AB  - With modern therapies, most children diagnosed with cancer are expected to reach
      adulthood. Therefore, there are large and ever-increasing numbers of children and
      young adults in our population who are survivors of childhood cancer. Many of the
      therapies responsible for improved cancer survival rates can also damage normal
      cells and tissues. As more children survive cancer, the physical and emotional
      costs of enduring cancer therapy become increasingly important. Although most
      childhood cancer survivors are now expected to survive, they remain at risk for
      relapse, second malignant neoplasms, organ dysfunction, and a negative
      psychologic impact. Individual risk is quite variable and is dependent on
      multiple factors including the type and site of cancer, the therapy utilized, and
      the individual's constitution. The risks are likely to change as we learn more
      about the specific long-term effects of cancer therapy, develop more refined and
      targeted therapies, and develop and apply more effective preventative strategies
      or therapeutic interventions. Guidelines for long-term follow-up have been
      established and are available to help facilitate appropriate monitoring of and
      care for potential late effects.

PMID- 16608371
TI  - Children hospitalized with skin and soft tissue infections: a guide to
      antibacterial selection and treatment.
AB  - Skin and soft tissue infections in children are an important cause for
      hospitalization. A thorough history and physical examination can provide clues to
      the pathogens involved. Collection of purulent discharge from lesions should be
      completed prior to initiating antimicrobial therapy, and results of bacteriologic
      studies (Gram stain and culture) should guide therapeutic decisions. The main
      pathogens involved in these infections are Staphylococcus aureus and group A beta
      hemolytic streptococci, but enteric organisms also play a role especially in
      nosocomial infections. Increasing antibacterial resistance is becoming a major
      problem in the treatment of these infections worldwide. Specifically, the rise of
      methicillin-resistant S. aureus and glycopeptide-resistant S. aureus pose
      challenges for the future. Infections of the skin and soft tissues can be broadly
      classified based on the extent of tissue involvement. Superficial infections such
      as erysipelas, cellulitis, bullous impetigo, bite infections, and periorbital
      cellulitis may require hospitalization and parenteral antibacterials. Deeper
      infections such as orbital cellulitis, necrotizing fasciitis, and pyomyositis
      require surgical intervention as well as parenteral antibacterial therapy.
      Surgery plays a key role in the treatment of abscesses and for the debridement of
      necrotic tissue in deep infections. Intravenous immunoglobulin, as an adjunctive
      therapy, can be helpful in treating necrotizing fasciitis. For most infections an
      antistaphylococcal beta-lactam antibacterial is first-line therapy. Third
      generation cephalosporins and beta-lactam/beta-lactamase inhibitor antibacterials
      as well as clindamycin or metronidazole are often required to provide broad
      spectrum coverage for polymicrobial infections.Special populations, such as
      immunocompromised children, those with an allergy to penicillins, and those that
      acquire infections in hospitals, require specific antibacterial strategies. These
      usually involve broader antimicrobial coverage with increased Gram-negative
      (including antipseudomonal) and anerobic coverage. In patients with a true
      allergy to penicillins, clindamycin and vancomycin play an important role in
      treating Gram-positive infections. Newer antibacterial agents, such as linezolid
      and quinupristin/dalfopristin, are increasingly being studied in children for the
      treatment of skin and soft tissue infections. These agents hold promise for the
      future especially in the treatment of highly resistant, Gram-positive organisms
      such as methicillin-resistant S. aureus, vancomycin-resistant S. aureus, and
      vancomycin-resistant enterococci.

PMID- 16608372
TI  - Valproate as a mainstay of therapy for pediatric epilepsy.
AB  - This article reviews relevant pharmacologic and clinical information gathered for
      valproate since it was introduced into clinical practice 37 years ago and the
      application of this information for the treatment of childhood epilepsy.
      Valproate is available for oral and parenteral use. Oral forms are almost
      completely bioavailable but the rate of absorption varies between formulations.
      The Chrono tablet formulation has not been adapted for children aged <6 years, in
      whom the oral solution or syrup, requiring two or three daily administrations,
      has been used until recently. A new formulation specifically adapted for
      children, Chronosphere, administrated once or twice daily, is a modified-release
      formulation of valproate that minimizes fluctuations in serum drug concentrations
      during a dosage interval. Plasma protein binding is 80-94% and tends to decrease
      with increasing drug concentration. Valproate elimination is markedly decreased
      in newborns compared with older children and adults. Elimination by
      glucuronidation only becomes fully effective by the age of 3-4 years. In children
      aged 2-10 years receiving valproate, plasma clearances are 50% higher than those
      in adults. Over the age of 10 years, pharmacokinetic parameters approximate those
      of adults. Valproate can increase plasma concentrations of concomitant drugs,
      such as phenobarbital and lamotrigine, by inhibiting their metabolism. As a
      result of its broad spectrum of efficacy in a wide range of seizure types and
      epilepsy syndromes, valproate is a drug of choice for children with newly
      diagnosed epilepsy (focal or generalized), idiopathic generalized epilepsy,
      epilepsies with prominent myoclonic seizures or with multiple seizure types, and
      photosensitive epilepsies. In the group of cognitive epilepsies, in which severe
      spike and wave discharges are accompanied by cognitive deterioration, valproate,
      ethosuximide, or both should be tested before using corticosteroids. In
      comparative trials with carbamazepine, phenytoin, and phenobarbital in focal
      epilepsy and with ethosuximide in absence epilepsy, valproate was as effective
      and showed a favorable tolerability profile, with minimal adverse cognitive and
      CNS effects. The low potential for paradoxical seizure aggravation and the long
      term efficacy of the drug are additional important factors that contribute to its
      excellent profile. Intravenous valproate may be effective for the treatment of
      convulsive and non-convulsive status epilepticus that is refractory to
      conventional drugs. In infants, potential benefits should be carefully weighed
      against the risk of liver toxicity. Gastrointestinal intolerance is a relatively
      frequent, dose-related adverse effect of the drug in children. Bodyweight
      increase and tremor may be observed in older children and adolescents. Despite
      the challenge of newer drugs, valproate remains a gold standard antiepileptic
      drug for the treatment of children.

PMID- 16608373
TI  - Pharmacodynamic evaluation of meropenem and cefotaxime for pediatric meningitis:
      a report from the OPTAMA program.
AB  - OBJECTIVE: To determine the probability of meropenem (Merrem, AstraZeneca
      Pharmaceuticals L.P., Wilmington, DE, USA) and cefotaxime (Claforan, Aventis
      Pharmaceuticals Inc., Bridgewater, NJ, USA) achieving bactericidal exposures in
      the cerebrospinal fluid against Streptococcus pneumoniae, Neisseria meningitidis,
      and Haemophilus influenzae. METHODS: A 5,000-patient Monte Carlo simulation in a
      population of 10-year-old children with meningitis was conducted. Pediatric
      pharmacokinetic data were derived from the literature. Pathogen minimum
      inhibitory concentrations (MICs) were obtained from common bacteria that had
      caused meningitis collected during pediatric clinical trials. Time above the MIC
      exposures in the cerebrospinal fluid was calculated. Bactericidal exposure or
      probability of target attainment was defined as 40% and 50% time above the MIC
      for meropenem and cefotaxime, respectively. High cumulative fractions of
      responses were defined as >90% probability of target attainment against the
      populations of bacteria. RESULTS: Meropenem was calculated to achieve 94.7%,
      94.3%, and 96.1% cumulative fractions of response against S. pneumoniae, H.
      influenzae, and N. meningitidis, respectively. Cefotaxime only achieved a high
      likelihood of bactericidal attainment against N. meningitidis (91.6%). Against S.
      pneumoniae and H. influenzae, cefotaxime was only calculated to achieve 84.3% and
      84.8% cumulative fractions of response, respectively. CONCLUSION: In a simulated
      population of 10-year-old children, meropenem had a high likelihood of attaining
      bactericidal exposures in the cerebrospinal fluid. Cefotaxime had a >90%
      cumulative fraction of response against only N. meningitidis. Therefore, at the
      doses simulated, meropenem may be a more appropriate empiric choice for the
      treatment of bacterial meningitis in pediatric patients presumed to be caused by
      these pathogens until culture and susceptibility data are available.

PMID- 16608374
TI  - Managing hyperlipidaemia in the elderly: special considerations for a population
      at high risk.
AB  - Numerous randomised, double-blind, placebo-controlled studies and observational
      studies have shown that HMG-CoA reductase inhibitors (statins) reduce mortality
      and major cardiovascular events in elderly high-risk persons with
      hypercholesterolaemia. The Heart Protection Study showed that statins reduced
      mortality and major cardiovascular events in elderly high-risk patients
      regardless of the initial level of serum lipids, age or sex. The updated National
      Cholesterol Education Program III guidelines state that in very high-risk
      individuals, a target serum low-density lipoprotein cholesterol (LDL-C) level of
      <70 mg/dL (1.8 mmol/L) is a reasonable clinical strategy. When a high-risk
      patient has hypertriglyceridaemia or low high-density lipoprotein-cholesterol,
      consideration can be given to combining a fibric acid derivative or nicotinic
      acid with an LDL-C-lowering drug. For moderately high-risk patients (two or more
      risk factors and a 10-year risk for coronary artery disease of 10-20%), the serum
      LDL-C should be reduced to <100 mg/dL (2.6 mmol/L). When LDL-C-lowering drug
      therapy is used to treat high-risk patients or moderately high-risk patients, the
      serum LDL-C should be reduced by at least 30-40%.

PMID- 16608375
TI  - Effect of personal and cultural beliefs on medication adherence in the elderly.
AB  - Approximately 50% of patients across all age groups with varied types of medical
      conditions do not adhere to their prescribed medication regimens. Medication
      nonadherence is common in older adults who are often prescribed medications for
      age-related chronic disorders. The purpose of this paper is to investigate the
      effect of personal and cultural beliefs on older adults' medication adherence
      through a review of research studies published in journals across different
      disciplines. A systematic literature search using ten databases found 14 articles
      meeting the inclusion criteria. Belief-laden variables including self-efficacy
      (i.e. the belief that one can perform a specific behaviour under differing
      conditions), medication efficacy, confidence in the physician's knowledge,
      perceptions about natural products and home remedies, beliefs of control (over
      one's health), and illness perceptions were found to be significantly related to
      medication adherence among older adults. However, several measurement, design and
      sampling problems were identified in this review. The majority of the studies in
      the review evaluated older adults' medication adherence by self-report and used
      cross-sectional designs and convenience samples. Future studies should utilise
      prospective longitudinal designs and a more objective measure of medication
      adherence, such as electronic event monitoring, when examining factors related to
      older adults' medication adherence. Future research should also evaluate belief
      related variables in larger and more ethnically diverse samples of older adults.
      Implications for assessment and intervention are evident from this literature
      review of the effect of personal and cultural beliefs on medication adherence in
      older adults.

PMID- 16608377
TI  - Economic cost of age-related macular degeneration: a review of recent research.
AB  - As the population of most developed countries ages so the prevalence of diseases
      such as age-related macular degeneration (AMD) are likely to increase. To
      facilitate planning and informed debate regarding making provisions for this
      disease it is important that we have a clear understanding of the economic impact
      of visual impairment associated with AMD. In this paper we assess the state of
      current knowledge based on a review of published evidence in scientific journals.
      Based on our assessment of the evidence we argue that the paucity of research
      studies on the subject and wide variation in estimates produced from the few
      studies available make it difficult to assess with confidence the likely average
      direct cost-of-illness associated with AMD. We further argue that significant
      gaps in our understanding of the costs of AMD (particularly in respect of
      indirect costs) also exist. Current research should be augmented by more
      comprehensive studies.

PMID- 16608376
TI  - Drug dosage in the elderly: dermatological drugs.
AB  - Drug pharmacokinetics and pharmacodynamics may be altered in the elderly. An
      important contribution is made by decreased renal function, but biotransformation
      in the liver may also play a role. Commonly prescribed dermatological drugs such
      as methotrexate and cetirizine are likely to be eliminated more slowly in the
      elderly and potentially hepatotoxic drugs such as itraconazole and acitretin
      should be used with caution. Altered drug distribution as a result of body
      composition changes can lead to prolonged half-life or higher plasma
      concentrations of many drugs. Higher prevalence of adverse drug reactions and
      multidrug regimens, and large interindividual variability in drug response make
      drug dosage and administration in the elderly challenging. New immunobiological
      agents such as alefacept, efalizumab and etanercept, which are approved for
      treatment of psoriasis, seem to be as well tolerated in the elderly as in younger
      patients. A recommended approach when prescribing drugs to the elderly would be
      to start with a small initial dose and to reduce the number of drugs administered
      simultaneously. It is crucial to simplify the drug regimen as much as possible in
      order to enhance drug management in the elderly. To improve pharmacotherapy in
      the elderly, we review age-related changes in pharmacokinetics that are likely to
      play a role in dermatological practice.

PMID- 16608378
TI  - A systematic review of the clinical and cost-effectiveness of memantine in
      patients with moderately severe to severe Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia and is characterised
      by a worsening of cognition, functional ability, and behaviour and mood. The
      objective of this study was to review the clinical and cost-effectiveness of
      memantine for the treatment of patients with moderately severe to severe AD. To
      achieve this, a systematic search and review of the clinical and cost
      effectiveness literature for memantine was undertaken. The literature search
      covered the period from the inception of MEDLINE, Cochrane Library, EMBASE and
      other electronic databases until July 2004. The search included randomised
      controlled trials (RCTs) and full economic evaluations that assessed the use of
      memantine in patients with moderately severe to severe AD. Two published RCTs
      were included in this review; in one of these trials the participants were
      already being treated with donepezil. The two RCTs showed benefit for patients
      receiving memantine compared with placebo on the outcome measures of the
      Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory
      modified for severe dementia, the Clinician's Interview-Based Impression of
      Change Plus Caregiver Input, and the Severe Impairment Battery, and that
      memantine appeared to be slightly more effective in patients already receiving a
      stable dose of donepezil. Five cost-effectiveness studies were included in the
      review. Although these studies reported cost reductions and improved outcomes
      with memantine, the evaluations were based on a number of assumptions. In
      conclusion, memantine appears to be beneficial when assessed using functional and
      global measurements. However, the effect of memantine on cognitive scores and
      behaviour and mood outcomes is less clear. Cost-effectiveness is dependent upon
      assumptions surrounding clinical effect and context-specific cost data.

PMID- 16608379
TI  - A pilot study evaluating the efficacy and safety of rivastigmine in patients with
      mixed dementia.
AB  - BACKGROUND AND OBJECTIVE: The two most common causes of dementia in the elderly
      are Alzheimer's disease (AD) and vascular dementia (VaD), which can coexist as
      mixed dementia. The object of this study was to assess the efficacy and safety of
      rivastigmine in patients with mixed dementia (AD with VaD). STUDY DESIGN: This 26
      week open-label pilot study was conducted at 19 centres in the US. To reduce
      bias, the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) raters were
      blinded to all efficacy measures and to patient dosage information. Patients were
      treated with rivastigmine and titrated to their highest tolerated dose, up to 12
      mg/day (6 mg twice daily). The primary efficacy measure was cognitive function
      assessed by the ADAS-Cog subscale (without the concentration/distractibility
      item, to be consistent with cognitive outcome measures used in previous
      rivastigmine trials). RESULTS: Forty-seven percent of patients treated with
      rivastigmine 6-12 mg/day demonstrated improvement on the ADAS-Cog at 26 weeks,
      with >25% of patients having a clinically significant improvement of > or =4
      points. Treatment with rivastigmine (6-12 mg/day) was well tolerated by the
      majority of patients. The most common adverse effects occurring in >10% of
      patients were nausea, vomiting, dizziness and diarrhoea. CONCLUSION: This pilot
      study suggests that rivastigmine treatment may have beneficial effects in the
      treatment of patients with mixed dementia.

PMID- 16608380
TI  - A taxonomy and economic consequences of nursing home falls.
AB  - BACKGROUND: Falls are a primary cause of injury and disability in the nursing
      home environment and can be costly to treat. We propose a taxonomy of nursing
      home falls that accounts for both the severity of fall consequences and the
      duration of the treatment episode. No other systematic approach of this kind has
      been previously described. METHODS: We defined a 9-level taxonomy of fall types
      and outcomes. Components of each fall category include resource use during the
      acute, convalescent, and long-term phases of treatment. Three variants of each
      category describe typical, best-case and worst-case fall episodes. Treatment
      costs were estimated for each fall category by applying unit costs from national
      databases and published sources to projected medical resource utilisation. Long
      term costs reflect adjustment in Medicare per diem reimbursement rates associated
      with change in patient status subsequent to the fall. RESULTS: The most common
      and least costly fall category was category 1 -- non-injurious, which accounted
      for 30% of falls and a 1-year cost of US dollars 319 per event (range US dollars
      71-550). The least common and most costly was fall category 9 -- multiple
      injuries, which accounted for 1% of falls and a 1-year cost of US dollars 22,368
      (range US dollars 9,969-64,382). CONCLUSIONS: The falls taxonomy represents a
      unique approach to estimating the cost of nursing home falls and offers a tool
      for evaluating the cost-effectiveness of fall prevention strategies. A validation
      study should be performed to confirm the magnitude of fall frequency and cost
      estimates.

PMID- 16608381
TI  - A randomised, controlled clinical trial evaluating changes in therapeutic
      efficacy and oxidative parameters after treatment with propionyl L-carnitine in
      patients with peripheral arterial disease requiring haemodialysis.
AB  - OBJECTIVE: We explored the efficacy of intravenous therapy with propionyl L
      carnitine in patients with both peripheral arterial disease (PAD) and chronic
      renal insufficiency requiring haemodialysis. METHODS: The trial was a randomised,
      double-blind, placebo-controlled trial. Sixty-four patients on haemodialysis (32
      per treatment arm) with chronic renal insufficiency and PAD were assigned to
      receive either intravenous propionyl L-carnitine 600 mg or placebo 3 times weekly
      for 12 months. The main outcome measures were the ankle/brachial index (ABI),
      plasma malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) concentrations, and the
      plasma nitrite/nitrate ratio (NO(2)/NO(3)); these were measured at baseline and
      at 6 and 12 months. RESULTS: Significant increases in ABI were observed in the
      propionyl L-carnitine group, whereas in the placebo group the reverse trend was
      seen. In patients treated with propionyl L-carnitine, significant progressive
      decreases were seen in plasma MDA, 4-HNE and the NO(2)/NO(3) ratio from baseline.
      In the placebo-treated group, only weakly significant or no differences were
      seen. CONCLUSION: Intravenous administration of propionyl L-carnitine to
      haemodialysis patients with PAD improves both haemodynamic flow and the oxidative
      profile.

PMID- 16608382
TI  - Improving access to medicines in poor countries: the role of universities.

PMID- 16608383
TI  - Getting it right: being smarter about clinical trials.

PMID- 16608384
TI  - Enrolling adolescents in research on HIV and other sensitive issues: lessons from
      South Africa.

PMID- 16608385
TI  - Nonhuman primate models for SARS.

PMID- 16608386
TI  - Singlet oxygen in plants--its significance and possible detection with double
      (fluorescent and spin) indicator reagents.
AB  - Direct detection of reactive oxygen species (ROS), especially singlet oxygen, in
      plants under stress conditions is of special importance, not only to identify
      primary events of oxidative damage, but also in studies exploring the potential
      role of ROS as signal molecules. Due to short life-times and diffusion distances
      of ROS, these tasks require highly reactive and selective indicator reagents,
      localized at the presumed site of production. In the present study, we compared
      four double sensors: ROS indicator reagents in which partial fluorescence
      quenching of a dansyl moiety occurs as a result of nitroxide radical formation
      from a sterically hindered amine constituent. Our experiments support the idea
      that shorter donor-acceptor distances within these molecules result in higher
      reactivity to ROS. The presence of a diethylaminoethyl side chain resulted in
      better selectivity to singlet oxygen: reagents lacking such substituent had an
      additional reactivity to superoxide anions, probably as a result of the formation
      of zwitterionic structures. Fluorescence localization studies of the indicator
      reagents in tobacco leaves and in Chlamydomonas cells show promising perspectives
      of their applications to plant stress studies.

PMID- 16608388
TI  - Compression of morbidity: the hype and the reality, part 1.

PMID- 16608387
TI  - Superoxidation of retinoic acid.
AB  - Atmospheric pressure chemical ionization mass spectroscopy (APCI-MS) was used to
      examine the light-induced oxidation products of retinoic acid under conditions
      that favor and preclude its aggregation. We observed that in conditions that
      favor aggregation, i.e. in aqueous solutions, retinoic acid undergoes
      superoxidation to yield highly oxidized species. Oxidation is limited, however,
      in the absence of such communication, i.e. when the polyene is fully solvated.
      From a comparison of the measured MS with that obtained from chemical oxidation
      of retinoic acid under conditions that promote radical oxidation and singlet
      oxygen-mediated oxidation, we conclude that superoxidation is mediated by
      reactive oxygen species other than singlet oxygen.

PMID- 16608389
TI  - Conjecture: Can continuous regeneration lead to immortality? Studies in the MRL
      mouse.
AB  - A particular mouse strain, the MRL mouse, has been shown to have unique healing
      properties that show normal replacement of tissue without scarring. The
      serendipitous discovery that the MRL mouse has a profound capacity for
      regeneration in some ways rivaling the classic newt and axolotl species raises
      the possibility that humans, too, may have an innate regenerative ability. We
      propose this mouse as a model for continuous regeneration with possible life
      extending properties. We will use the classical "immortal" organism, the hydra,
      for comparison and examine those key phenotypes that contribute to their
      immortality as they are expressed in the MRL mouse versus control mouse strains.
      The phenotypes to be examined include the rate of proliferation and the rate of
      cell death, which leads to a continual turnover in cells without an increase in
      mass.

PMID- 16608390
TI  - Sustained stromal stem cell self-renewal and osteoblastic differentiation during
      aging.
AB  - We have reported the isolation of a unique subpopulation of human stromal cells
      from bone marrow termed marrow-isolated adult multilineage inducible (MIAMI)
      cells. The expression of embryonic stem cell markers SSEA-4, Oct-4, Rex-1, and
      telomerase reverse transcriptase indicates the developmentally immature status of
      these cells. They resemble primitive stem cells in their capacity to
      differentiate, at least in vitro, into mature-like cells from all three germ
      layers. MIAMI cells are characterized by a unique molecular profile that
      distinguishes them from other marrow stromal cell populations. Although the
      frequency of MIAMI cells, among all marrow nucleated cells, decreases from 0.01%
      at age 3 to 0.0018% at age 45, their numbers remain unchanged after age 45. The
      level of expression of the markers characteristic of MIAMI cells remains constant
      independent of age and gender. In long-term in vitro expansion experiments aging
      increased the population doubling time by about 30%, whereas specific in vitro
      differentiation of MIAMI cells toward osteoblastic cells was unaffected. Because
      the oxygen tension in bone marrow ranges from 1% to 7%, we examined the role of
      oxygen tension in regulating the capacity of MIAMI cells to self-renew and
      maintain their pluripotentiality during long-term culture. Low oxygen tension
      upregulated mRNAs for primitive embryonic stem cell markers. Our results suggest
      that maintaining developmentally primitive human cells in vitro at low oxygen
      tension is more physiologic and favors stemness. For osteoblastic
      differentiation, gap-junctional communication mediated by connexin43 is required.
      Its inhibition not only blocked osteoblastic differentiation but stimulated the
      adipocytic differentiation.

PMID- 16608391
TI  - To make a new intestinal mucosa.
AB  - A number of clinical conditions are caused by disorders affecting the mucosal
      lining of the gastrointestinal tract. Some patients suffer from a loss of mucosal
      surface area due to congenital defects or due to surgical resections ("short
      bowel syndrome"). Other patients have inborn or acquired defects of certain
      mucosal functions (e.g., glucose-galactose malabsorption, bile acid
      malabsorption). Many patients with these mucosal disorders could be more
      effectively treated if healthy mucosa were available in larger quantities as a
      replacement or functional supplement. We therefore developed methods to
      transplant mucosal stem cells from one part of the intestine to another and to
      make bioengineered intestinal mucosa. We generated an animal model of bile acid
      malabsorption using rats that underwent resection of the distal 25% of their
      small intestine (ileum). This resulted in significant losses of bile acids with
      the fecal excretions in these animals. We subsequently harvested ileal stem cell
      clusters from neonatal donors, removed the mucosa from a segment of proximal
      intestine (jejunum), and implanted the stem cell clusters into the debrided
      segment of jejunum. After four weeks, the animals had developed a functional
      "neomucosa." We inserted the "neo-ileal" segment into continuity as a substitute
      ileum. Postoperative measurements of fecal bile acid excretion showed that we
      were able to reverse the malabsorption syndrome in this model. This was the first
      reported neo-mucosa-based treatment of a malabsorption syndrome in vivo. We
      subsequently studied different biodegradable PGA and PLLA scaffoldings to
      generate bioengineered intestinal mucosa. We implanted these materials into
      omentum of rats and were able to identify a PGA/PLLA hybrid material on which
      engraftment rates of 36% of the available surface area could be achieved. Most
      recently, we developed a novel technique that permits direct observation of cell
      biomaterial interactions after implantation into omentum or intestine in vivo.
      This method will help to optimize engraftment conditions for stem cell clusters
      on biomaterials.

PMID- 16608392
TI  - Transfection of CCE mouse embryonic stem cells with EGFP and BDNF genes by the
      electroporation method.
AB  - Embryonic stem (ES) cells are pluripotent cells that can differentiate into a
      wide variety of cell types. This has made them an attractive source of donor
      cells for developmental studies and cell therapy. Blocking the differentiation of
      ES cells in culture and using them in clinical applications requires genetic
      manipulation of the cells. The aim of the present study was to transfect CCE ES
      cells with EGFP and BDNF genes, in which pcDNA3-hBDNF-v5 and pIRES2-EGFP plasmids
      were used, respectively. Transformation of DH5alpha competent bacteria by the
      plasmids was done. Then the plasmids were purified and transfected into ES cells
      using the electroporation method. The expression of the EGFP gene was confirmed
      using invert fluorescent microscopy; accordingly, RT-PCR was used for the BDNF
      gene. The latter was evaluated by extracting the total RNA from the transfected
      cells. cDNA was obtained by using reverse transcriptase and was amplified by
      specific primers. The products of the PCR were separated and visualized by
      agarose gel electrophoresis. Both techniques revealed a successful transfection
      of CCE ES cells by both plasmids. The obtained data indicated that
      electroporation is an efficient method for transfection of CCE ES cells.

PMID- 16608393
TI  - Glucose-induced replicative senescence in mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) show great promise for use in a variety of cell
      based therapies. Because isolated primary mesenchymal stem cells are low in
      numbers, in vitro expansion is necessary. However, the expansion potential is
      limited and in vitro aging leads to loss of multipotency and replicative
      senescence. Stress induced by culture conditions is likely to be a major cause of
      replicative senescence and reduced multipotency of MSC and optimization of
      culture conditions might be able to reduce this. Caloric restriction (CR) is the
      only established method to delay aging and extend lifespan. In vitro caloric
      restriction experiments are rare, but have demonstrated beneficial effects.
      Therefore, we investigated the effect of culture medium glucose concentration on
      the proliferative and differentiation potential of mesenchymal stem cells.
      Reduction in glucose concentrations led to decreased apoptosis and an increased
      rate of MSC proliferation and increased the number and size of fibroblastic
      colonies in the colony-forming unit assay.

PMID- 16608394
TI  - Gene therapy that safely targets and kills tumor cells throughout the body.
AB  - The authors studied the therapeutic value of Sindbis vectors for advanced
      metastatic cancer by using a variety of clinically accurate mouse models and
      demonstrated through imaging, histological, and molecular data that Sindbis
      vectors systemically and specifically infect/detect and kill metastasized tumors
      in vivo, leading to significant suppression of tumor growth and enhanced
      survival. Use of two different bioluminescent genetic markers for the IVIS
      Imaging System (Xenogen Corp., Alameda, CA) permitted demonstration of an
      excellent correlation between vector delivery and metastatic locations in vivo.
      Sindbis tumor specificity is not attributable to a species difference between
      human tumor and mouse normal cells. Sindbis virus is known to infect mammalian
      cells using the Mr 67,000 laminin receptor, which is elevated in tumor versus
      normal cells, and downregulated expression of laminin receptor with small
      interfering RNA significantly reduces the infectivity of Sindbis vectors. Tumor
      overexpression of the laminin receptor may explain the specificity and efficacy
      that Sindbis vectors demonstrate for tumor cells in vivo. Laser capture
      microdissection of mouse tumor implants showed equivalent laminin receptor
      expression levels in the different tumor metastases in the peritoneal cavity.
      Incorporation of antitumor cytokine genes such as interleukin-12 and interleukin
      15 genes enhances the efficacy of the vector. These results suggest that Sindbis
      viral vectors may be promising agents for both specific detection and growth
      suppression of metastatic ovarian cancer.

PMID- 16608395
TI  - Catechin-vanilloid synergies with potential clinical applications in cancer.
AB  - A cancer-specific cell surface protein, tNOX, has been identified as a target for
      low-dose cell killing (apoptosis) of cancer cells by green tea catechins and
      Capsicum vanilloid combinations. This protein is uniquely associated with all
      forms of cancer and is absent from normal cells and tissues. Its activity is
      correlated with cancer growth. When blocked, cancer cells fail to enlarge after
      division and eventually die. Among the most potent and effective inhibitors of
      tNOX are naturally occurring polyphenols exemplified by the principal green tea
      catechin (-)-epigallocatechin gallate (EGCg) and the vanilloid capsaicin.
      Catechin-vanilloid combinations are 10 to 100 times more effective than either
      catechins or vanilloids alone. Vector-forced overexpression of tNOX cDNA and
      antisense has demonstrated that the tNOX target is both necessary and sufficient
      to explain the anticancer properties of green tea catechins alone and in
      vanilloid-containing combinations. The necessity and sufficiency of tNOX was
      validated as the catechin target with transgenic mice overexpressing the
      processed form of tNOX. Transgenic mice grew faster and the increased growth
      caused by tNOX overexpression was blocked by EGCg in the drinking water. A
      catechin-vanilloid mixture where one 350-mg capsule is equivalent to 16 cups of
      green tea in its ability to inhibit tNOX and growth of cancer cells in culture is
      undergoing clinical evaluation as a therapeutic aid for cancer patients.

PMID- 16608396
TI  - Multilocus genotypes spanning estrogen metabolism associated with breast cancer
      and fibroadenoma.
AB  - We investigated inherited polymorphic variation in genes spanning estrogen
      metabolism (10 SNPs [single nucleotide polymorphism]) to distinguish multilocus
      genotypes associated with breast cancer (n = 393), benign breast lesions (n =
      154), and low risk (n = 1936). Three latent classification GoM extreme type
      groups represented the data: (a) fibroadenoma, and infrequent SRD5A2 and VDR
      alleles; (b) postmenopausal breast cancer, and infrequent CYP1A1-1 and CYP1A1-2
      alleles (both over-represented infrequent alleles for CYP17, CYP19-3, and COMT);
      and (c) women at intrinsically low risk. Carriage of the respective multilocus
      genotypes increased risk 25-fold. We conclude that GoM latent classification may
      be useful to identify genetic risk sets and estimate risk for individuals.

PMID- 16608397
TI  - Analysis of telomere length and telomerase activity in tree species of various
      lifespans, and with age in the bristlecone pine Pinus longaeva.
AB  - Normal somatic cells have a finite replicative capacity, and with each cell
      division telomeres progressively shorten, unless the telomerase enzyme is
      present. The bristlecone pine, Pinus longaeva, is the oldest known living
      eukaryotic organism, with the oldest on record turning 4770 years old in 2005.
      The results from our study of telomere length and telomerase activity in samples
      (needle, root, core) from P. longaeva with age, and in other tree species of
      various lifespans, support the hypothesis that both increased telomere length and
      telomerase activity may contribute to the increased lifespan and longevity
      evident in long-lived pine trees (i.e., 2000- to 5000-year lifespan) compared
      with medium-lived (400- to 500-year lifespan) and short-lived (100- to 200-year
      lifespan) pine trees, as well as in P. longaeva with age.

PMID- 16608398
TI  - Mitochondrial dysfunction and cell senescence: cause or consequence?
AB  - The mitochondrial theory of aging remains to date one of the most popular
      theories of aging. One major model of aging is replicative senescence, where the
      irreversible loss of division potential of somatic cells occurs after a more or
      less constant number of cell divisions. Few data are available concerning the
      role of mitochondria in this model. Here, we review evidence supporting the
      involvement of mitochondria in replicative senescence and a possible link to
      telomere biology. Moreover, we suggest that this process might be more complex
      than originally formulated, because variations in nuclear gene expression
      involved in mitochondrion nucleus cross-talk are observed in both senescence and
      immortalization.

PMID- 16608399
TI  - Chromatin modification and senescence: linkage by tumor suppressors?
AB  - Senescence was originally defined as a state associated with cell cycle arrest
      that occurs after cells have undergone an intrinsically limited number of
      divisions in vitro. Much evidence indicates that senescence occurs as a
      consequence of the internal stress signal generated from shortening telomeres on
      the ends of chromosomes. However, more recently, various forms of extrinsic
      stresses have been shown to induce a markedly similar senescent phenotype that
      includes changes in chromatin structure and gene expression. Chromatin structure
      is subject to many forms of modification that affect transcription, gene
      silencing, cell proliferation, and senescence, much of which involves imposition
      of an epigenetic histone code. Several genes in the p53, Rb, and ING (inhibitor
      of growth) pathways affect cell senescence and are capable of regulating gene
      expression through chromatin remodeling. This suggests that a link may exist
      between chromatin modification and cellular senescence through the activity of
      proteins typically defined as tumor suppressors.

PMID- 16608400
TI  - Amyloid-beta immunotherapy for the prevention and treatment of Alzheimer disease:
      lessons from mice, monkeys, and humans.
AB  - Alzheimer disease (AD), the most common form of dementia, is without an effective
      cure or preventive treatment. Recently, amyloid-beta protein (Abeta) has become a
      major therapeutic target. Many efforts are underway to either reduce the
      production of Abeta or enhance its clearance. In 1999, Schenk and colleagues
      first showed that active immunization with full-length Abeta lowered cerebral
      Abeta levels in transgenic mice. These findings have been confirmed and extended
      in various transgenic mouse models of AD using both active and passive Abeta
      immunization. Cognitive improvement also has been reported in association with
      active and passive Abeta vaccination in AD-like mouse models, even in the absence
      of significant reductions in cerebral Abeta loads. In 2004, the authors reported
      that active immunization with full-length Abeta in aged nonhuman primates,
      Caribbean vervets, reduced cerebral Abeta levels and gliosis. Proposed mechanisms
      of Abeta clearance by immunotherapy include disruption of Abeta aggregates, Abeta
      phagocytosis by microglia, neutralization of Abeta oligomers at the synapse, and
      increased efflux of Abeta from brain to blood. A phase IIa clinical trial was
      halted in 2002 because of the appearance of meningoencephalitis in approximately
      6% of the AD patients. Although the exact cause of these adverse events is
      unknown, the immunogen, full-length Abeta1-42, may have been recognized as a self
      antigen leading to an autoimmune response in some patients. Limited cognitive
      stabilization and apparent plaque clearance have been reported in subsets of
      patients who generated antibody titers. Currently, a passive immunization trial
      with a recombinant humanized monoclonal Abeta antibody is underway in humans. In
      the meantime, the authors are developing novel Abeta peptide immunogens for
      active immunization to target Abeta B cell epitope(s) and avoid Abeta-specific T
      cell reactions in order to generate a safe and effective AD vaccine. The authors
      remain optimistic about the potential of such a vaccine for the prevention and
      treatment of AD.

PMID- 16608401
TI  - Synaptic pathology in the brain cortex of old monkeys as an early alteration in
      senile plaque formation.
AB  - Synaptic numeric density (Nv), average size (area: S), surface density (Sv) and
      number of synapses/neurone (Syn/Neur) were morphometrically measured in frontal
      (FC) and temporal (TC) cortex of adult and old monkeys. Sv was constant, a clear
      age-related trend to decrease by Nv and increase by S were observed in both areas
      investigated. Syn/Neur significantly decreased in TC of aged animals (-21.1%),
      whereas FC showed a not significant reduction (-2.6%). The present data support
      the hypothesis of an increased sensitivity to deterioration of TC synapses in
      aged monkeys, which might constitute a predisposing condition to the development
      of senile plaques.

PMID- 16608402
TI  - Membership in genetic groups predicts Alzheimer disease.
AB  - The multiple polymorphisms contributing to Alzheimer disease (AD) have been
      difficult to identify. Three essentially sufficient risk sets were found using a
      fuzzy latent classification statistical model; that is, grade-of-membership
      analysis, and genotypes for APOE, APOCI, LDLr, cystatin C, and cathepsin D (180
      cases, 120 controls). These were: (a) CST3:GA and CTSD:CT; (b) APOE44 and
      LDLr8:GG and LDLr13:TT; and (c) APOE34 and LDLr13:TC. Consonance with one of the
      groups and high aggregate membership carried >800-fold elevated risk for AD. The
      absence of these combinations defined low risk. APOE3/- with heterozygous
      promoter and receptor genotypes predicted long life without dementia.

PMID- 16608403
TI  - Level and distribution of microtubule-associated protein-2 (MAP2) as an index of
      dendritic structural dynamics.
AB  - Optical density of MAP2 immunoreactivity (OD), the ratio between the MAP2 stained
      area/total test area (area fraction: AF), the total length of MAP2 labeled
      profiles (TL) and the ratio perimeter/area of the immunostained profiles
      (pleomorphism index [PI]) were measured by quantitative immunohistochemistry in
      the brain of rats of different ages. In old rats versus young and adult animals,
      OD and AF were significantly lower, whereas PI was significantly higher, in
      dentate gyrus molecular layer, CA1 stratum radiatum and olfactory bulb. These
      findings lend support to the many converging results on the higher vulnerability
      to aging of the CNS areas featuring higher plasticity.

PMID- 16608404
TI  - Association between the HLA-A2 allele and Alzheimer disease.
AB  - In the elderly, the most common cause of dementia is Alzheimer disease (AD),
      which is responsible for the age-related progressive neurodegenerative
      inflammatory condition mediated by the disease. It has been seen that several
      genetic and environmental factors are involved in AD onset. Epidemiologic data
      suggest that some genetic determinants of AD might reside in those polymorphisms
      that regulate immune inflammatory responses, such as the major histocompatibility
      complex (MHC). Therefore, several MHC polymorphisms have been in the spotlight of
      a large number of AD association studies. A possible association of HLA-A2 allele
      with increased susceptibility to AD has been the subject of debate for more than
      20 years, even if the results of these studies, in the various populations, are
      discordant. Thus, to gain insight in this matter, the authors have studied the
      HLA-A2 allele for a possible association with sporadic AD in a homogeneous
      population of Italian patients. For this reason, the distribution of HLA-A2
      allele in patients with sporadic AD and controls was analyzed by PCR-SSP assay.
      The results demonstrated a significant difference in the frequency of HLA-A2
      allele between patients with sporadic AD and controls (46% versus 38%). Thus,
      these data confirm a positive role of HLA-A2 allele in the risk of developing AD.
      However, some of the observed discrepancies may result from clinical or genetic
      heterogeneity of the populations under study or methodologic biases. Besides,
      whenever external agents such as viruses play a role, these might different in
      the various populations leading to various associations. However, it has to be
      taken into account that there are many molecular HLA-A2 subtypes with different
      frequencies in various populations. Therefore, further studies should include
      molecular typing of HLA-A2 subtypes.

PMID- 16608405
TI  - Structural synaptic remodeling in the perirhinal cortex of adult and old rats
      following object-recognition visual training.
AB  - The ultrastructural features of layer II synapses in the perirhinal cortex of
      adult (4- to 6-month-old) and old (25- to 27-month-old) rats exposed to a six
      session object recognition visual training were investigated by morphometric
      methods. The comparative analysis showed a higher synaptic numeric density, a
      lower synaptic average area, and a lower percentage of megasynapses (S > 0.5
      microm2) in old trained rats versus controls, and a higher percentage of small (S
      < 0.15 microm2) junctions in adult trained rats versus controls. The more marked
      synaptic remodeling underlying memory consolidation in the perirhinal cortex of
      old rats might reflect a pre-existing lower dynamic status.

PMID- 16608406
TI  - The nACHR4 594C/T polymorphism in Alzheimer disease.
AB  - Alzheimer disease (AD) is the most common form of dementia with complex etiology
      and multifactorial origin. Although several neurochemical deficits have been
      described in AD patients, explanation of the nature of the cognitive disturbance
      is focused on the "cholinergic hypothesis." The neuronal nicotinic acetylcholine
      receptor (neuronal nAChR) belongs to the superfamily of ionic channel activated
      by ligand. This paper presents a population-based population association study,
      testing the hypothesis that variants of the nAChR gene confer genetic
      susceptibility to AD. The authors analyzed two cohorts constituted by 60 controls
      and 80 AD patients in which significant increase of 594T polymorphism in patients
      affected by AD versus controls was found. However, further studies are necessary
      to confirm this polymorphism trend and to establish the polymorphism
      functionality and its correlation with behavioral and cognitive deficit.

PMID- 16608407
TI  - Immunorejuvenation in the elderly.
AB  - Dysregulated T-cell-mediated immunity contributes materially to the increased
      susceptibility to infectious disease, and possibly cancer, in the elderly. One
      hallmark of this state of "immunosenescence" in humans is the predominance of
      large clones of peripheral T cells with limited antigen receptor heterogeneity
      and a corresponding contraction of diversity in the T-cell antigen recognition
      repertoire. Surprisingly, a major driving force for these clonal expansions in
      humans is cytomegalovirus. The lifelong chronic antigenic stress caused by
      infection with this persistent activating virus results in clonal exhaustion of
      specific CD8 T cells, and their acquisition of a state of anergy and apoptosis
      resistance similar in many respects, and, the authors believe for similar
      reasons, to that commonly seen in the tumor-specific T cells of cancer patients.
      This excess of dysfunctional cells is indirectly immunosuppressive by filling the
      "immunologic space" and shrinking the T-cell repertoire for new antigens, as well
      as directly suppressive via cytokine secretion. It is associated with the
      "immunologic risk profile" predicting 2- and 4-year mortality in longitudinal
      studies of very old people. Therefore, it is hypothesized that deletion of such
      accumulations of dysfunctional cells would be beneficial to the individual. It
      may be possible to distinguish functional CMV-specific cells (which are essential
      to maintain immunosurveillance) from dysfunctional ones by their expression of
      certain surface molecules. This, coupled with methods directed at reinvigorating
      the thymus (e.g., use of interleukin 7), and targeting CMV by pharmacologic and
      immunotherapeutic interventions might result in a degree of "immunorejuvenation"
      sufficient to take elderly individuals out of the risk category and thereby
      extend healthy longevity.

PMID- 16608408
TI  - Antibody quality in old age.
AB  - There is very little change in the quantity of antibodies people produce, of any
      isotype, with age. However, there is a change in the quality of the antibody
      response. Older people produce fewer antibodies that are specific for the
      activating pathogen or vaccine. At the same time, the number of nonspecific
      antibodies increases. Quite often these antibodies have self-reactivity (e.g.,
      anti-dsDNA). The appearance of these antibodies is not associated with pathogenic
      autoimmune disease, although it is true that the incidence of some autoimmune
      diseases increases with age. The authors postulate that the process of antibody
      affinity maturation is compromised in old age. No evidence was found that the
      process of hypermutation is compromised with age. However, using graph theory to
      study the dynamics of a germinal center selection process, a decrease in the
      extent of selection occurring in the germinal centers of mucosal tissue was
      observed with age. This is a tissue-specific phenomenon because the decrease was
      not seen in the germinal centers of spleen. Because selection of highly specific
      cells in the germinal center depends on a number of factors (number and quality
      of founder cells, help from T cells, and follicular dendritic cells) these need
      to be investigated further to determine what is needed to improve the affinity
      mutation process.

PMID- 16608409
TI  - Immunomodulatory vaccines against autoimmune diseases.
AB  - Vaccines are for healthy people, to prevent them from becoming ill. Such
      prophylactic vaccines have been a great success. Therapeutic vaccines become more
      and more important, especially as life expectancy increases. Efforts to develop
      vaccines against such diseases as cancer, AIDS, hepatitis, tuberculosis,
      Alzheimer disease, and mad cow disease have not yet reached the stage where they
      can be successfully used on a daily basis. However, significant progress has been
      made in the realm of autoimmune diseases, resulting (at least in one case) in an
      immunomodulatory vaccine against multiple sclerosis that was developed in the
      author's laboratory, and that is in daily use by about 100,000 patients. The drug
      or therapeutic vaccine against the exacerbating-remitting type of multiple
      sclerosis is a copolymer of four amino acid residues, denoted Copaxone, which are
      related to myelin basic protein. This paper discusses Copaxone as well as a
      candidate immunomodulatory vaccine against myasthenia gravis, a peptide derived
      from the nicotinic acetylcholine receptor. Copolymer 1 (Cop 1, glatiramer
      acetate, Copaxone) is a synthetic amino acid random copolymer that is
      immunologically cross-reactive with myelin basic protein and suppresses
      experimental allergic encephalomyelitis in several animal species. Cop 1 slows
      the progression of disability and reduces the relapse rate in exacerbating
      remitting multiple sclerosis patients. Cop 1 is a potent inducer of T helper 2
      (Th2) regulatory cells in mice and humans; and Th2 cells are found in both the
      brains and spinal cords of Cop 1-treated mice and humans. MG and experimental
      autoimmune MG are T cell-regulated, antibody-mediated autoimmune diseases. Two
      peptides, representing sequences of the human AChR-alpha-subunit, p195-212 and
      p259-271, are immunodominant T-cell epitopes in MG patients and two strains of
      mice. Altered peptide ligand, composed of the randomly arranged two single amino
      acid analogs inhibits in vitro and in vivo MG-associated autoimmune responses.
      The active suppression is mediated by the CD4+ CD25+ immunoregulatory cells and
      is associated with the downregulation of Th1-type cytokines and upregulation of
      the secretion of IL-10 and the immunosuppressive cytokine transforming growth
      factor beta.

PMID- 16608410
TI  - A novel approach to thymic rejuvenation in the aged.
AB  - With advancing age, the mammalian thymus undergoes involution, a progressive loss
      of architectural integrity and lymphoid cellularity that results in reduced T
      lymphopoiesis. Thymic involution also is associated with extreme malnutrition and
      states of immune deficiency, such as active HIV infection, after chemotherapy, or
      during pregnancy. Immune recovery appears to require restoration of normal
      thymopoiesis. Although several means are known to increase thymic cellularity in
      the aged, including systemic administration of hormones, androgen ablation, and
      thymic tissue transplantation, each suffers from specific limitations that
      prevent widespread application. This paper presents a novel approach to
      rejuvenate T cell differentiation in the aged that employs intrathymic
      implantation of engineered stromal cells. Two different proteins have been
      examined for their impact on thymopoiesis after delivery by somatic cell
      implantation. Intrathymic injection of IL-7-producing stromal cells enhances the
      earliest specification steps of T cell development, resulting in the increased
      representation of pro-T cells in the aged thymus. In contrast, increasing the
      intrathymic levels of sonic hedgehog diminishes this aspect of T cell poiesis.

PMID- 16608411
TI  - Biology of longevity: role of the innate immune system.
AB  - Genetic factors play a relevant role in the attainment of longevity because they
      are involved in cell maintenance systems, including the immune system. In fact,
      longevity may be correlated with optimal functioning of clonotypic and natural
      immunity. The aging of the immune system, known as immunosenescence, is the
      consequence of the continuous attrition caused by chronic antigenic overload. The
      antigenic load results in the progressive generation of inflammatory responses
      involved in age-related diseases. Most of the parameters influencing
      immunosenescence appear to be under genetic control, and immunosenescence fits
      with the basic assumptions of evolutionary theories of aging, such as
      antagonistic pleiotropy. In fact, by neutralizing infectious agents the immune
      system plays a beneficial role until reproduction and parenting. However, by
      determining chronic inflammation, it can be detrimental later in life, a period
      largely unforeseen by evolution. In particular, the data coming from the long
      lived male population under study show that genetic polymorphisms responsible for
      a low inflammatory response might result in an increased chance of long lifespan
      in an environment with a reduced pathogen burden. Such a modern and healthy
      environment also permits a lower grade of survivable atherogenic inflammatory
      response.

PMID- 16608412
TI  - Memory B cell subpopulations in the aged.
AB  - The literature on immunosenescence has focused mainly on T cell impairment. With
      the aim of gaining insight into B cell immunosenescence, the authors investigated
      the serum IgD levels in 24 young and 21 old people and analyzed their
      relationship with the number of CD19+CD27+ memory cells. Serum IgD were
      quantified by the use of radial immunodiffusion and the lymphocyte population
      CD19+CD27+ was identified by a FACScan flow cytometer. Serum IgD levels were
      significantly lower (p < 0.0001) in old subjects, and the percentage of
      CD19+CD27+ lymphocytes were significantly increased (p = 0.01) in old subjects.
      Finally, a significant negative correlation was found (p = 0.01) between serum
      concentrations of IgD and CD19+CD27+. The present results show that the levels of
      IgD are negatively age-related to the amount of B memory cells. This suggests
      that the B repertoire available to respond to new antigenic challenges is
      decreased in the elderly. In fact, many memory IgD- B cells fill immunologic
      space, and the number of naive IgD+ B cells is dramatically decreased. Therefore,
      these preliminary results suggest that a decrease of naive IgD+CD27- B cells and
      a concomitant increase of memory IgD-CD27+ B cells could represent hallmarks of B
      immunosenescence, might provide biomarkers related to the lifespan of humans, and
      could be useful for the evaluation of antiaging treatments.

PMID- 16608413
TI  - Analysis of candidate genes in celiac disease: a tool to identify life
      threatening associated genes?
AB  - The authors have recently reported that celiac patients show a proinflammatory
      cytokine genetic profile characterized by the contemporaneous presence of both
      the tumour necrosis factor-alpha-308A and the interferon-gamma +874T allele
      positive genotypes. The same alleles are considered risk factors for aging
      associated disease, whereas an anti-inflammatory cytokine genotype profile might
      be associated with an extended life expectancy. This paper reports data on the
      1249-1250InsACAA/Non-Ins transforming growth factor (TGF)-beta2, a
      multifunctional anti-inflammatory cytokine, polymorphism distribution in 88
      celiac disease (CD) patients, 99 age- and sex-matched controls, and 28 >95-year
      old healthy subjects living in western Sicily. These data demonstrate that
      genotype frequencies of CD patients are not different from that of age-matched
      and >95-year-old healthy control subjects. These data might suggest that TGF
      beta2 polymorphism is not involved in the complex genotypes associated with
      successful or unsuccessful aging. In addition, one can speculate that the
      genotype profile associated with CD susceptibility might be detrimental for
      longevity, and studies of this CD genetic asset might point to a candidate gene
      for antiaging strategies.

PMID- 16608415
TI  - Validated worldwide supercentenarians for 2005.

PMID- 16608414
TI  - Analysis of HLA-DQA, HLA-DQB frequencies in a group of Sardinian centenarians.
AB  - Human leukocyte antigen (HLA) alleles, regulating type and intensity of the
      immune response, might influence life expectancy. In previous case-control
      studies the authors have demonstrated that both HLA-DR and -DQ alleles are not
      associated with longevity in the Sardinian population. On the other hand,
      association studies are subjected (as part of the homogeneity of the population
      in terms of geographic origin) to a number of possible confounding factors.
      Therefore, the authors typed the HLA-DQA1 and HLA-DQB1 alleles in 24 sibs (age
      range 85 to 97) of 17 centenarians by PCR-SSP. Sib pair analysis showed
      nonsignificant differences between the observed and expected percentage of DQA*
      or DQB1* allele sharing. Therefore, these data strengthen the view that class II
      HLA genes have a marginal effect, if any, on the complex longevity trait.

PMID- 16608417
TI  - AIDS vaccine efficacy trials: expand capacity and prioritize. 'Throughout Africa,
      Asia and Latin America state-of-the-art clinics and laboratories...exist where, 4
      years ago, there were none'.

PMID- 16608418
TI  - An adolescent and adult formulation combined tetanus, diphtheria and five
      component pertussis vaccine.
AB  - Pertussis causes substantial morbidity among adolescents and adults, as well as
      other persons in contact with affected individuals. In the context of widespread
      childhood immunization, vaccination of adolescents and adults is a relatively new
      strategy for reducing the disease in all age groups. ADACEL is a tetanus
      diphtheria-acellular pertussis combination vaccine (incorporating pertussis
      toxoid, filamentous hemagglutinin, pertactin and fimbriae type 2 and 3 antigens)
      formulated for use in adolescents and adults based on similar products designed
      for infants and children. ADACEL vaccine is approved for use in Australia,
      Canada, Germany and the USA, and has been demonstrated to induce robust immune
      responses and acceptable levels of reactogenicity in clinical trials.
      Surveillance data from Canada, where ADACEL vaccine has been used in adolescents
      and adults in conjunction with ongoing childhood vaccination for several years,
      indicate an enhanced overall reduction in pertussis disease.

PMID- 16608419
TI  - An ounce of prevention on a budget: a nonprofit approach to developing vaccines
      against neglected diseases.
AB  - This article provides a perspective on vaccine development for neglected tropical
      diseases in the nonprofit setting, with particular emphasis on recombinant
      protein vaccines. The Human Hookworm Vaccine Initiative is discussed as a model
      product development public-private partnership, and the major challenges are
      covered that accompany antigen selection, gene cloning, fermentation and
      purification process development, assay development, vaccine formulation and
      testing and clinical evaluation for those developing vaccines, especially against
      neglected tropical diseases, in the nonprofit sector. Throughout this
      perspective, special emphasis is placed on the growing promise that product
      development public-private partnerships hold for developing vaccines for the
      world's poorest people.

PMID- 16608420
TI  - PSA-based vaccines for the treatment of prostate cancer.
AB  - Prostate cancer is the second leading cause of cancer-related death among men in
      the USA. Vaccine strategies represent a novel therapeutic approach. One potential
      target for a prostate cancer vaccine is prostate-specific antigen, owing to its
      restricted expression in prostate cancer and normal prostatic epithelial cells. A
      number of prostate-specific antigen-specific epitopes have been identified that
      can activate cytotoxic T lymphocytes and, in turn, result in the killing of tumor
      targets by the peptide-specific cytotoxic T lymphocytes. Strategies employed in
      clinical trials consist of dendritic cell vaccines, recombinant protein and
      recombinant DNA vaccines, as well as viral vector delivery of vaccines. New
      approaches incorporating a combination of a vaccine with traditional treatments
      for prostate cancer are also being investigated.

PMID- 16608421
TI  - Current progress in the development of a cell-based vaccine for the immunotherapy
      of acute myeloid leukemia.
AB  - Evidence that immunological control contributes to the elimination of residual
      leukemia has emerged from allogeneic hematopoietic stem cell transplantation.
      This review assesses the current understanding of immunobiology of acute myeloid
      leukemia and how dendritic cells and T cells may be harnessed using in vitro and
      in vivo priming techniques. Preclinical and clinical dendritic cell vaccine
      trials reported to date are considered and the prospects for immunotherapy with
      dendritic cell-based vaccine constructs evaluated.

PMID- 16608422
TI  - MG7 mimotope-based DNA vaccination for gastric cancer.
AB  - Gastric cancer is still one of the leading causes of cancer-related death
      worldwide. Prevention and treatment of gastric cancer through vaccination has
      been difficult owing to lack of a specific target and poor immunity. A number of
      vaccination strategies have been used to augment immune responses against gastric
      cancer and some progress has been made. In a series of studies, the authors have
      focused on gastric cancer vaccination approaches based on MG7 mimotopes, which
      are mimicry epitopes selected from phage-displayed oligopeptide libraries with a
      gastric cancer cell-specific monoclonal antibody, MG7-Ab. Strategies employed in
      these studies include viral or plasmid vectors in combination with carrier
      sequence or unmethylated CpG with synthetic peptides in nanoemulsion. The results
      demonstrated that MG7 mimotopes could effectively and specifically induce both
      cellular and humoral immune reactions and in vivo antitumor responses. In
      particular, a four-MG7 mimotope DNA vaccine was found to elicit much stronger
      antitumor immune responses in mice compared with its single-mimotope counterpart.
      These encouraging findings might pave the way for the development of novel MG7
      antigen-based vaccination approaches for human gastric cancer. The review also
      discusses other immune-enhancing vaccination strategies for gastric cancer.

PMID- 16608423
TI  - Sensitization of malignant glioma to chemotherapy through dendritic cell
      vaccination.
AB  - Drug resistance represents a major cause of chemotherapy failure in patients with
      cancer. The characterization of the molecular pathways involved in drug
      resistance has provided new targets to circumvent or reverse chemotherapy
      resistance. Many of these target proteins are often overexpressed in human glioma
      and have been identified as tumor antigens, which implicate the development of
      immunotherapy as a therapeutic strategy. Dendritic cells (DCs) are the most
      potent antigen-presenting cells of the immune system and have been demonstrated
      to stimulate antibody and cell-mediated immune responses against tumor-associated
      antigens. Ex vivo-generated and tumor antigen-loaded DCs have been successfully
      introduced to clinical vaccination protocols, which have proven to be feasible
      and effective in some glioma patients. Most importantly, immunotherapy followed
      by chemotherapy could significantly increase 2-year survival in malignant glioma
      patients, which obviously demonstrates that DC vaccination could increase the
      sensitivity of tumor cells to chemotherapy. This review focuses on recent
      advances in the identification of tumor-associated antigen in glioma, as well as
      novel insights into their biological function related to drug resistance. These
      insights may provide the rationale for a novel strategy of a DC cancer vaccine
      that sensitizes tumor cells to chemotherapy. In addition, the current research
      status and the future direction of a DC-based vaccine to treat glioma in animal
      models and clinical trials will also be discussed.

PMID- 16608424
TI  - Plant-derived vaccines: a look back at the highlights and a view to the
      challenges on the road ahead.
AB  - The sobering reality is that each year, 33 million children remain unvaccinated
      for vaccine-preventable diseases. Universal childhood vaccination would have
      profound effects on leveling the health inequities in many parts of the world. As
      an alternative to administration of vaccines by needle and syringe, oral vaccines
      offer significant logistical advantages, as the polio eradication campaign has
      demonstrated. Over the past decade, the expression of subunit vaccine antigens in
      plants has emerged as a convenient, safe and potentially economical platform
      technology, with the potential to provide a novel biotechnological solution to
      vaccine production and delivery. As this technology has come of age, many
      improvements have been made on several fronts, as a growing number of research
      groups worldwide have extensively investigated plants as factories for vaccine
      production. This review attempts to highlight some of the achievements over the
      past 15 years, identify some of the potential problems and discuss the promises
      that this technology could fulfill.

PMID- 16608425
TI  - Prevention and treatment of respiratory syncytial virus infection in infants: an
      update.
AB  - Respiratory syncytial virus (RSV) is a serious pathogen causing significant
      mortality and morbidity, especially in premature infants and infants with chronic
      lung disease or significant congenital heart disease. Therapy for RSV infection
      is essentially supportive, although several new compounds are under
      investigation. Therefore, immunoprophylaxis to prevent severe RSV disease in high
      risk infants assumes great significance. Palivizumab, a humanized monoclonal
      antibody to RSV, significantly reduces hospitalization in the first 6 months in
      premature infants born at less than 35 weeks, infants less than 24 months of age
      with chronic lung disease and requiring treatment in the last 6 months, and in
      children 24 months or younger with hemodynamically significant heart disease. A
      new ultrapotent anti-RSV antibody (MEDI-524) appears to be more effective in
      animals than palivizumab and is undergoing clinical evaluation. There has been
      considerable progress in the development of vaccines; namely subunit, live
      attenuated, genetically recombinant virus and polypeptide vaccines. Plasmid DNA
      vaccines coding for parts of the F and G surface glycoproteins and vaccinia
      vector vaccines are also being evaluated. Maternal immunization has the potential
      to prevent RSV disease in early infancy. RSV prophylaxis has seen tremendous
      progress in the last decade.

PMID- 16608426
TI  - Immunization strategies for the control of serogroup C meningococcal disease in
      developed countries.
AB  - In developed countries, the epidemiology of serogroup C meningococcal disease is
      characterized by unpredictable outbreaks and a bimodal distribution of cases,
      with the highest incidence rate among those below 1 year of age and a second peak
      in teenagers. Serogroup C meningococcal conjugate vaccines elicit a thymus
      dependent immunological response that is already present in young infants and is
      characterized by the production of protective antibodies and the development of
      memory. Results from immunogenicity and effectiveness studies indicate that
      waning of immunity occurs over time, and the protection conferred by vaccination
      before 1 year of age seems to be shortlived. Very different control strategies
      have been implemented throughout the world and existing vaccination schedules may
      not be optimal. A schedule consisting of a first dose around 1 year of age and a
      second dose around 12 years of age seems to be a very cost-effective option in
      most epidemiological scenarios.

PMID- 16608427
TI  - Bacillus Calmette-Guerin vaccination and infant mortality.
AB  - When the bacillus Calmette-Guerin (BCG) vaccine was introduced in the 1920s, it
      was suggested that BCG occasionally had nonspecific beneficial effects on
      mortality beyond the specific protection against tuberculosis. Considering that
      BCG has since then become the most used vaccine in the world, surprisingly few
      studies have been undertaken into the effect of BCG on general mortality and
      morbidity. Recent studies suggest that BCG has beneficial nontargeted effects on
      general infant morbidity and mortality in low-income countries, often with the
      most pronounced effect among girls. These observational findings are supported by
      early trials in which children were randomized or alternated to BCG vaccination.
      Furthermore, a BCG scar and a positive tuberculin reaction are related to better
      survival among BCG-vaccinated children in low-income countries, especially for
      girls. The findings are not explained by frailty bias, in other words, that
      healthy children are more likely to receive BCG vaccination. A nonspecific,
      gender-differential effect of BCG on general infant mortality may have large
      implications for tuberculosis vaccine research and routine vaccination policy.

PMID- 16608428
TI  - Successes and remaining challenges after 10 years of varicella vaccination in the
      USA.
AB  - Beginning in 1995, universal varicella vaccination was recommended in the USA for
      all children aged 12-18 months, and all susceptible adolescents and adults. Many
      physicians were initially sceptical about the need to prevent primary varicella.
      However, with passage of state daycare and school entry mandates for varicella
      immunization, national varicella vaccination rates increased to approximately 90%
      by 2004. Several studies have demonstrated concomitant reductions in varicella
      related healthcare utilization, costs and varicella-related mortality among
      children in the vaccinated age group, as well as adults. Remaining challenges
      include: first, outbreaks of 'breakthrough' varicella in vaccinated populations,
      which may prompt a second-dose recommendation, and second, possible increases in
      the incidence of secondary varicella (zoster) among adults whose natural immunity
      may wane in the absence of endemic varicella. The latter concern highlights the
      importance of a promising new varicella vaccine for older adults that may be
      licensed and recommended in the next 2 years.

PMID- 16608429
TI  - Report from the 2nd Annual US HUPO Meeting on the HUPO Human Plasma Proteome
      Project.

PMID- 16608431
TI  - The Plasma Proteome: High Abundance versus Low Abundance. January 10-11, 2006,
      San Diego, CA, USA.

PMID- 16608432
TI  - Role and challenges of proteomics in pharma and biotech: technical, scientific
      and commercial perspective.
AB  - Contemporary proteomics, currently in its exponential growth phase, is a
      bewildering array of tools. Proteomic methods are the result of a convergence of
      rapidly improving mass spectrometry technologies, protein chemistry and
      separation sciences, genomics and bioinformatics. Strides in improving proteomics
      technologies to map and measure proteomes and subproteomes are being made.
      However, no single proteomic platform appears ideally suited to address all
      research needs or accomplish ambitious goals satisfactorily. However, proteomics
      is in a unique position to contribute to protein discovery and to public health
      in terms of better biomarkers, diagnostics and treatment of disease. While the
      potential is great, many challenges and issues remain to be solved. Fundamental
      issues, such as biological variability, pre-analytic factors and analytical
      reproducibility, remain to be resolved. Neither an all-genetic approach nor an
      all-proteomic approach will solve biological complexity. Proteomics will be the
      foundation for constructing and extracting useful knowledge to pharma and biotech
      depicted in the following path: data --> structured data --> information -->
      information architecture --> knowledge --> useful knowledge.

PMID- 16608433
TI  - Proteomic dissection of DNA polymerization.
AB  - DNA polymerases replicate the genome by associating with a range of other
      proteins that enable rapid, high-fidelity copying of DNA. This complex of
      proteins and nucleic acids is termed the replisome. Proteins of the replisome
      must interact with other networks of proteins, such as those involved in DNA
      repair. Many of the proteins involved in DNA polymerization and the accessory
      proteins are known, but the array of proteins they interact with, and the spatial
      and temporal arrangement of these interactions, are current research topics. Mass
      spectrometry is a technique that can be used to identify the sites of these
      interactions and to determine the precise stoichiometries of binding partners in
      a functional complex. A complete understanding of the macromolecular interactions
      involved in DNA replication and repair may lead to discovery of new targets for
      antibiotics against bacteria and biomarkers for diagnosis of diseases, such as
      cancer, in humans.

PMID- 16608434
TI  - Putting proteomics on target: activity-based profiling of ubiquitin and ubiquitin
      like processing enzymes.
AB  - Modification of proteins with ubiquitin (Ub) and Ub-like modifiers (Ubls) plays a
      fundamental role in cell biology. As a consequence, proteomics-based efforts were
      developed to characterize proteins that are modified by Ub or Ubls. A more
      focused functional proteomics strategy relies on active-site probes based on the
      Ub/Ubl scaffold, which specifically targets Ub/Ubl-processing enzymes. Activity
      based profiling with such tools led to the identification of novel gene products
      with Ub/Ubl-processing activity and uncovered novel control mechanisms regulating
      their activity. This review discusses recent advances in chemistry-based
      functional proteomics applications, and how this information can provide a
      framework for drug development against Ub/Ubl-processing enzymes.

PMID- 16608435
TI  - Type 1 diabetes: entering the proteomic era.
AB  - During the last decade, a major breakthrough in the field of proteomics has been
      achieved. This review describes available techniques for proteomic analyses, both
      gel and non-gel based, particularly concentrating on relative quantification
      techniques. The principle of the different techniques is discussed, highlighting
      the advantages and drawbacks of recently available visualization methods in gel
      based assays. In addition, recent developments for quantitative analysis in non
      gel-based approaches are summarized. This review focuses on applications in Type
      1 diabetes. These mainly include proteomic studies on pancreatic islets in animal
      models and in the human situation. Also discussed are mass spectrometry-based
      studies on T-cells, and studies on the development of diagnostic markers for
      diabetic nephropathology by capillary electrophoresis coupled to mass
      spectrometry.

PMID- 16608436
TI  - Proteomics and heart disease: identifying biomarkers of clinical utility.
AB  - Cardiovascular disease is the leading cause of mortality and morbidity in the
      industrialized world. Total worldwide deaths due to this disease are currently
      estimated at 17 million per year, and this number is expected to increase over
      the next several decades. To address this epidemic, a major effort has begun to
      develop new cardiovascular disease markers through the use of proteomic analysis,
      the global study of proteins. This review discusses strategies, recent
      technological advances and other issues in plasma/serum biomarker discovery for
      cardiovascular diseases. Emphasis lies on the needs for standardizing specimen
      collection, methods for reducing plasma proteome complexity to subproteomes,
      selection of appropriate technology platforms and strategies to evaluate
      candidates by multiplexed immune assays. The overall goal of this effort is to
      identify serum biomarkers for diagnosis, therapeutic monitoring and risk
      stratification of cardiovascular diseases.

PMID- 16608437
TI  - Protein primary structure using orthogonal fragmentation techniques in Fourier
      transform mass spectrometry.
AB  - Proteomics analysis using tandem mass spectrometry requires informative backbone
      fragmentation of peptide ions. Collision-activated dissociation (CAD) of cations
      alone is not sufficiently informative to satisfy all requirements. Thus, there is
      a need to supplement CAD with a complementary fragmentation technique. Electron
      capture dissociation (ECD) is complementary to collisional excitation in terms of
      the cleavage of a different bond (N-Calpha versus C-N bond) and other properties.
      CAD-ECD combination improves protein identification and enables high-throughput
      de novo sequencing of peptides. ECD and its variants are also useful in mapping
      labile post-translational modifications in proteins and isomer differentiation;
      for example, distinguishing Ile from Leu, iso-Asp from Asp and even D- from L
      amino acid residues.

PMID- 16608438
TI  - All-trans retinoic acid down-regulates human albumin gene expression through the
      induction of C/EBPbeta-LIP.
AB  - ATRA (all-trans retinoic acid), which is a major bioactive metabolite of vitamin
      A and a potent regulator of development and differentiation, mediates down
      regulation of the human albumin gene. However, the mechanism of ATRA-mediated
      down-regulation is not well understood. In the present study, deletion analysis
      and luciferase assays demonstrate that ATRA causes a marked decrease in the
      activity of the albumin promoter, the region between nt -367 and -167 from the
      transcription start site, where C/EBP (CCAAT/enhancer-binding protein)-binding
      sites are tightly packed, is indispensable for ATRA-mediated down-regulation.
      ChIP (chromatin immunoprecipitation) assays revealed that in vivo binding of
      C/EBPalpha to the region markedly decreases upon incubation with ATRA, whereas
      ATRA treatment marginally increases the recruitment of C/EBPbeta. We found that
      ATRA has the ability to differentially and directly induce expression of a
      truncated isoform of C/EBPbeta, which is an LIP (liver-enriched transcriptional
      inhibitory protein) that lacks a transactivation domain, and to increase the
      binding activity of C/EBPbeta-LIP to its response element. Overexpression of
      C/EBPbeta-LIP negatively regulates the endogenous expression of albumin, as well
      as the activity of the albumin promoter induced by C/EBP transactivators such as
      C/EBPalpha and full-length C/EBPbeta. In conclusion, we propose a novel model for
      down-regulation of the albumin gene, in which ATRA triggers an increase in the
      translation of C/EBPbeta-LIP that antagonizes C/EBP transactivators by
      interacting with their binding sites in the albumin promoter.

PMID- 16608439
TI  - Growth suppression induced by Notch1 activation involves Wnt-beta-catenin down
      regulation in human tongue carcinoma cells.
AB  - BACKGROUND INFORMATION: Involvement of Notch1 signalling in several cancers is
      well known, but its role in human tongue squamous cell carcinoma, one of the most
      common carcinomas of the human oral cavity, remains poorly characterized.
      RESULTS: Our studies demonstrated that constitutively over-expressed active
      Notch1, via stable transfection of exogenous ICN (intracellular fragment of
      Notch), resulted in growth suppression of the human tongue cancer cell line
      Tca8113 in vitro and in vivo, accompanied by G(0)-G(1) cell cycle arrest and
      apoptosis. Moreover, down-regulation of beta-catenin protein expression was
      observed in Tca8113 cells stably expressing active Notch1. Activated Notch1 also
      led to dramatic increase in p21(WAF1/CIP1) and p53 expression with decreases in
      Skp2 (S-phase kinase-associated protein 2) and Bcl-2 (B-cell lymphocytic
      leukaemia proto-oncogene 2) expression, which may participate in the induction of
      apoptosis and cell cycle arrest. CONCLUSIONS: Since the effects of the Notch1
      pathway are cell-type specific and context-dependent in cell types where Notch1
      has an anti-proliferative effect, down-regulation of Wnt/beta-catenin signalling
      may be one of the mechanisms which induces apoptosis and cell cycle arrest.

PMID- 16608440
TI  - Atorvastatin normalizes endothelial function in healthy smokers.
AB  - Endothelial function is known to predict cardiovascular disease. The aim of the
      present study was to examine whether endothelial function in smokers with normal
      cholesterol levels could be normalized by treatment with 80 mg of atorvastatin in
      comparison with a control group. Healthy smokers (n=20) and non-smokers (n=20)
      were randomized to receive 80 mg of atorvastatin or placebo in an open randomized
      cross-over study, followed by measurement of endothelial functional [FMD (flow
      mediated dilation)]. At baseline, smokers had a lower FMD compared with the non
      smoking group (2.2+/-0.5 and 4.5+/-0.8% respectively; P<0.05). In the smoking
      group, FMD increased significantly (P<0.05) to 4.0+/-0.8% during treatment with
      atorvastatin and returned to basal levels during placebo (2.3+/-0.6%). In the non
      smoking group, FMD was unaffected by both atorvastatin and placebo. The net
      change of total cholesterol or LDL (low-density lipoprotein)-cholesterol was not
      associated with the net change in FMD when the study group was considered as a
      whole or the smoking group was considered separately. In conclusion, improved
      endothelial function was observed in a group of smokers when they were received
      80 mg of atorvastatin, whereas atorvastatin had no effect on endothelial function
      in the non-smoking group. The improved FMD among smokers was independent of the
      decrease in LDL-cholesterol during atorvastatin treatment. The results show that
      poor endothelial function in smokers with normal lipid levels can be improved by
      a statin treatment.

PMID- 16608441
TI  - The life-extending gene Indy encodes an exchanger for Krebs-cycle intermediates.
AB  - A longevity gene called Indy (for 'I'm not dead yet'), with similarity to
      mammalian genes encoding sodium-dicarboxylate cotransporters, was identified in
      Drosophila melanogaster. Functional studies in Xenopus oocytes showed that INDY
      mediates the flux of dicarboxylates and citrate across the plasma membrane, but
      the specific transport mechanism mediated by INDY was not identified. To test
      whether INDY functions as an anion exchanger, we examined whether substrate
      efflux is stimulated by transportable substrates added to the external medium.
      Efflux of [14C]citrate from INDY-expressing oocytes was greatly accelerated by
      the addition of succinate to the external medium, indicating citrate-succinate
      exchange. The succinate-stimulated [14C]citrate efflux was sensitive to
      inhibition by DIDS (4,4'-di-isothiocyano-2,2'-disulphonic stilbene), as
      demonstrated previously for INDY-mediated succinate uptake. INDY-mediated efflux
      of [14C]citrate was also stimulated by external citrate and oxaloacetate,
      indicating citrate-citrate and citrate-oxaloacetate exchange. Similarly, efflux
      of [14C]succinate from INDY-expressing oocytes was stimulated by external
      citrate, alpha-oxoglutarate and fumarate, indicating succinate-citrate, succinate
      alpha-oxoglutarate and succinate-fumarate exchange respectively. Conversely, when
      INDY-expressing Xenopus oocytes were loaded with succinate and citrate,
      [14C]succinate uptake was markedly stimulated, confirming succinate-succinate and
      succinate-citrate exchange. Exchange of internal anion for external citrate was
      markedly pH(o)-dependent, consistent with the concept that citrate is co
      transported with a proton. Anion exchange was sodium-independent. We conclude
      that INDY functions as an exchanger of dicarboxylate and tricarboxylate Krebs
      cycle intermediates. The effect of decreasing INDY activity, as in the long-lived
      Indy mutants, may be to alter energy metabolism in a manner that favours lifespan
      extension.

PMID- 16608442
TI  - Biochemical characterization of detergent-resistant membranes: a systematic
      approach.
AB  - Lateral segregation of cholesterol- and sphingomyelin-rich rafts and
      glycerophospholipid-containing non-raft microdomains has been proposed to play a
      role in a variety of biological processes. The most compelling evidence for
      membrane segregation is based on the observation that extraction with non-ionic
      detergents leads to solubilization of a subset of membrane components only.
      However, one decade later, a large body of inconsistent detergent-extraction data
      is threatening the very concept of membrane segregation. We have assessed the
      validity of the existing paradigms and we show the following. (i) The
      localization of a membrane component within a particular fraction of a sucrose
      gradient cannot be taken as a yardstick for its solubility: a variable
      localization of the DRMs (detergent-resistant membranes) in sucrose gradients is
      the result of complex associations between the membrane skeleton and the lipid
      bilayer. (ii) DRMs of variable composition can be generated by using a single
      detergent, the increasing concentration of which gradually extracts one
      protein/lipid after another. Therefore any extraction pattern obtained by a
      single concentration experiment is bound to be 'investigator-specific'. It
      follows that comparison of DRMs obtained by different detergents in a single
      concentration experiment is prone to misinterpretations. (iii) Depletion of
      cholesterol has a graded effect on membrane solubility. (iv) Differences in
      detergent solubility of the members of the annexin protein family arise from
      their association with chemically different membrane compartments; however, these
      cannot be attributed to the 'brick-like' raft-building blocks of fixed size and
      chemical composition. Our findings demonstrate a need for critical re-evaluation
      of the accumulated detergent-extraction data.

PMID- 16608443
TI  - Effects of mediators on the laccase biosensor response in paracetamol detection.
AB  - An enzyme electrode suitable for paracetamol detection was developed by
      immobilizing laccase on a dissolved-oxygen probe surface. The immobilization
      procedure was achieved by means of gelatin, which was then cross-linked with
      glutaraldehyde. The measurement was based on the detection of oxygen consumption
      in relation to analyte oxidation. The optimum experimental conditions for the
      biosensor were investigated and the system was calibrated for paracetamol. Also
      the effects of three different mediators, namely HBT (1-hydroxybenzotriazole),
      VLA [violuric acid (5-isonitrosobarbituric acid)] and TEMPO (2,2',6,6'
      tetramethylpiperidine-N-oxyl radical) were tested for the biosensor's response.
      As a result, it was observed that HBT has a remarkable effect on the signal by
      providing more oxygen consumption during the enzymatic reaction. A linear
      relationship between sensor responses and analyte concentrations was obtained
      over the concentration range 2.0-15.0 microM, whereas, in the presence of the
      mediator HBT, this range became 0.5-3.0 microM.

PMID- 16608444
TI  - Comparative transcriptomics -- model species lead the way.

PMID- 16608445
TI  - Ozone -- a significant threat to future world food production?

PMID- 16608446
TI  - On modelling Rubisco turnover: dynamics and applicability.

PMID- 16608447
TI  - Endobacteria or bacterial endosymbionts? To be or not to be.

PMID- 16608448
TI  - A remarkable moment in Australian biogeography.

PMID- 16608449
TI  - How plants cope with complete submergence.
AB  - Flooding is a widespread phenomenon that drastically reduces the growth and
      survival of terrestrial plants. The dramatic decrease of gas diffusion in water
      compared with in air is a major problem for terrestrial plants and limits the
      entry of CO(2) for photosynthesis and of O(2) for respiration. Responses to avoid
      the adverse effects of submergence are the central theme in this review. These
      include underwater photosynthesis, aerenchyma formation and enhanced shoot
      elongation. Aerenchyma facilitates gas diffusion inside plants so that shoot
      derived O(2) can diffuse to O(2)-deprived plant parts, such as the roots. The
      underwater gas-exchange capacity of leaves can be greatly enhanced by a thinner
      cuticle, reorientation of the chloroplasts towards the epidermis and increased
      specific leaf area (i.e. thinner leaves). At the same time, plants can outgrow
      the water through increased shoot elongation, which in some species is preceded
      by an adjustment of leaf angle to a more vertical position. The molecular
      regulatory networks involved in these responses, including the putative signals
      to sense submergence, are discussed and suggestions made on how to unravel the
      mechanistic basis of the induced expression of various adaptations that alleviate
      O(2) shortage underwater.

PMID- 16608450
TI  - Forest-tree population genomics and adaptive evolution.
AB  - Forest trees have gained much attention in recent years as nonclassical model
      eukaryotes for population, evolutionary and ecological genomic studies. Because
      of low domestication, large open-pollinated native populations, and high levels
      of both genetic and phenotypic variation, they are ideal organisms to unveil the
      molecular basis of population adaptive divergence in nature. Population genomics,
      in its broad-sense definition, is an emerging discipline that combines genome
      wide sampling with traditional population genetic approaches to understanding
      evolution. Here we briefly review traditional methods of studying adaptive
      genetic variation in forest trees, and describe a new, integrated population
      genomics approach. First, alleles (haplotypes) at candidate genes for adaptive
      traits and their effects on phenotypes need to be characterized via sequencing
      and association mapping. At this stage, functional genomics can assist in
      understanding gene action and regulation by providing detailed transcriptional
      profiles. Second, frequencies of alleles in native populations for causative
      single-nucleotide polymorphisms are estimated to identify patterns of adaptive
      variation across heterogeneous environments. Population genomics, through
      deciphering allelic effects on phenotypes and identifying patterns of adaptive
      variation at the landscape level, will in the future constitute a useful tool, if
      cost-effective, to design conservation strategies for forest trees.

PMID- 16608451
TI  - A comparison of the Thlaspi caerulescens and Thlaspi arvense shoot
      transcriptomes.
AB  - Whole-genome transcriptome profiling is revealing how biological systems are
      regulated at the transcriptional level. This study reports the development of a
      robust method to profile and compare the transcriptomes of two nonmodel plant
      species, Thlaspi caerulescens, a zinc (Zn) hyperaccumulator, and Thlaspi arvense,
      a nonhyperaccumulator, using Affymetrix Arabidopsis thaliana ATH1-121501 GeneChip
      arrays (Affymetrix, Santa Clara, CA, USA). Transcript abundance was quantified in
      the shoots of agar- and compost-grown plants of both species. Analyses were
      optimized using a genomic DNA (gDNA)-based probe-selection strategy based on the
      hybridization efficiency of Thlaspi gDNA with corresponding A. thaliana probes.
      In silico alignments of GeneChip probes with Thlaspi gene sequences, and
      quantitative real-time PCR, confirmed the validity of this approach.
      Approximately 5000 genes were differentially expressed in the shoots of T.
      caerulescens compared with T. arvense, including genes involved in Zn transport
      and compartmentalization. Future functional analyses of genes identified as
      differentially expressed in the shoots of these closely related species will
      improve our understanding of the molecular mechanisms of Zn hyperaccumulation.

PMID- 16608452
TI  - Heavy metal stress and leaf senescence induce the barley gene HvC2d1 encoding a
      calcium-dependent novel C2 domain-like protein.
AB  - By comparing cDNA populations derived from chromium-stressed primary leaves of
      barley (Hordeum vulgare L.) with controls, differentially expressed cDNA
      fragments could be identified. The deduced amino acid sequence of one of these
      cDNAs [named 'C2 domain 1' (HvC2d1)] exhibits a motif that is similar to the
      known C2 domain and a nuclear localization signal (NLS). Expression of this
      member of a novel class of plant C2 domain-like proteins was studied using real
      time PCR, and subcellular localization was investigated using green fluorescent
      protein (GFP) fusion constructs. Calcium binding was analysed using a (45)Ca(2+)
      overlay assay. HvC2d1 was transiently induced after exposure to different heavy
      metals and its mRNA accumulated during the phase of leaf senescence. HvC2d1
      expression responded to changes in calcium levels caused by the calcium ionophore
      A23187 and to treatment with methylviologen resulting in the production of
      reactive oxygen species (ROS). Using overexpressed and purified HvC2d1, the
      binding of calcium could be confirmed. Chimeric HvC2d1-GFP protein was localized
      in onion epidermal cells at the plasma membrane, cytoplasm and the nucleus. After
      addition of calcium ionophore A23187 green fluorescence was only visible in the
      nucleus. The data suggest a calcium-dependent translocation of HvC2d1 to the
      nucleus. A possible role of HvC2d1 in stress- and development-dependent
      signalling in the nucleus is discussed.

PMID- 16608454
TI  - Are heat and cold resistance of arctic species affected by successive extreme
      temperature events?
AB  - Extreme temperature events are projected to increase in frequency in a future
      climate. As successive extremes could occur more frequently, patches of
      vulnerable tundra vegetation were exposed to two consecutive heat waves (HWs) of
      10 d each, with a 5-d recovery period in between. Surface temperatures during the
      HWs were increased approximately 6 degrees C using infrared irradiation sources.
      In three of the four target species (Pyrola grandiflora, Polygonum viviparum and
      Carex bigelowii), plant conditions improved upon the first exposure. Depending on
      species, leaf relative growth, leaf chlorophyll content or maximal photochemical
      efficiency was increased. In P. grandiflora the positive effects of the heat on
      the photosynthetic apparatus led to augmented net photosynthesis. By contrast,
      Salix arctica responded mainly negatively, indicating species-specific responses.
      During the second HW, leaf mortality suddenly increased, indicating that the heat
      stress induced by the extreme events lasted too long and negatively influenced
      the species resistance to high temperature. After the HWs, when plants were
      exposed to (low) ambient temperatures again, plant performance deteriorated
      further, indicating possible loss of cold resistance.

PMID- 16608453
TI  - Hypersensitivity to cytoskeletal antagonists demonstrates microtubule
      microfilament cross-talk in the control of root elongation in Arabidopsis
      thaliana.
AB  - Elongation of diffusely expanding plant cells is thought to be mainly under the
      control of cortical microtubules. Drug treatments that disrupt actin
      microfilaments, however, can reduce elongation and induce radial swelling. To
      understand how microfilaments assist growth anisotropy, we explored their
      functional interactions with microtubules by measuring how microtubule disruption
      affects the sensitivity of cells to microfilament-targeted drugs. We assessed the
      sensitivity to actin-targeted drugs by measuring the lengths and diameters of
      expanding roots and by analysing microtubule and microfilament patterns in the
      temperature-sensitive Arabidopsis thaliana mutant microtubule organization 1
      (mor1-1), along with other mutants that constitutively alter microtubule arrays.
      At the restrictive temperature of mor1-1, root expansion was hypersensitive to
      the microfilament-disrupting drugs latrunculin B and cytochalasin D, while
      immunofluorescence microscopy showed that low doses of latrunculin B exacerbated
      microtubule disruption. Root expansion studies also showed that the botero and
      spiral1 mutants were hypersensitive to latrunculin B. Hypersensitivity to actin
      targeted drugs is a direct consequence of altered microtubule polymer status,
      demonstrating that cross-talk between microfilaments and microtubules is critical
      for regulating anisotropic cell expansion.

PMID- 16608455
TI  - Conifers in cold environments synchronize maximum growth rate of tree-ring
      formation with day length.
AB  - Intra-annual radial growth rates and durations in trees are reported to differ
      greatly in relation to species, site and environmental conditions. However, very
      similar dynamics of cambial activity and wood formation are observed in temperate
      and boreal zones. Here, we compared weekly xylem cell production and variation in
      stem circumference in the main northern hemisphere conifer species (genera Picea,
      Pinus, Abies and Larix) from 1996 to 2003. Dynamics of radial growth were modeled
      with a Gompertz function, defining the upper asymptote (A), x-axis placement
      (beta) and rate of change (kappa). A strong linear relationship was found between
      the constants beta and kappa for both types of analysis. The slope of the linear
      regression, which corresponds to the time at which maximum growth rate occurred,
      appeared to converge towards the summer solstice. The maximum growth rate
      occurred around the time of maximum day length, and not during the warmest period
      of the year as previously suggested. The achievements of photoperiod could act as
      a growth constraint or a limit after which the rate of tree-ring formation tends
      to decrease, thus allowing plants to safely complete secondary cell wall
      lignification before winter.

PMID- 16608456
TI  - Pigments, photosynthesis and photoinhibition in two amphibious plants:
      consequences of varying carbon availability.
AB  - In the present study, we investigated the effects of CO(2) availability on
      photosynthesis, photoinhibition and pigmentation in two species of amphibious
      plants, Lobelia cardinalis and Nesaea crassicaulis. The plants were grown
      emergent under atmospheric conditions and submerged under low and high CO(2)
      availability. Compared with Lobelia, Nesaea had thin leaves and few stomata in
      all CO(2) treatments. While Lobelia expressed no variation in anthocyanin content
      among treatments, Nesaea produced high concentrations of anthocyanin when
      submerged. Lobelia photosynthesis increased in response to increasing CO(2)
      availability, and photoinhibition was negatively related to xanthophyll content.
      By contrast, Nesaea photosynthesis was highest under submerged conditions, and
      there was no relationship between photoinhibition and the xanthophyll content. We
      conclude that the response of Lobelia to varying CO(2) availability is similar to
      that of terrestrial plants and that this species relies on the xanthophyll cycle
      for nonphotochemical quenching (NPQ) and protection against photoinhibition. By
      contrast, the thin leaves, few stomata and low levels of chlorophylls and
      accessory pigments in Nesaea, relative to Lobelia, suggest adaptation to a
      submerged habitat. While Nesaea does not seem to rely on the xanthophyll cycle or
      other xanthophylls for NPQ, some role of anthocyanins in the protection against
      photoinhibition cannot be ruled out, owing to its effect as a sunscreen and as an
      efficient quencher of free radicals.

PMID- 16608457
TI  - Enhancement of rice canopy carbon gain by elevated CO(2) is sensitive to growth
      stage and leaf nitrogen concentration.
AB  - Increasing our understanding of the factors regulating seasonal changes in rice
      canopy carbon gain (C(gain): daily net photosynthesis -- night respiration) under
      elevated CO(2) concentrations ([CO(2)]) will reduce our uncertainty in predicting
      future rice yields and assist in the development of adaptation strategies. In
      this study we measured CO(2) exchange from rice (Oryza sativa) canopies grown at
      c. 360 and 690 micromol mol(-1)[CO(2)] in growth chambers continuously over three
      growing seasons. Stimulation of C(gain) by elevated [CO(2)] was 22-79% during
      vegetative growth, but decreased to between -12 and 5% after the grain-filling
      stage, resulting in a 7-22% net enhancement for the whole season. The decreased
      stimulation of C(gain) resulted mainly from decreased canopy net photosynthesis
      and partially from increased respiration. A decrease in canopy photosynthetic
      capacity was noted where leaf nitrogen (N) decreased. The effect of elevated
      [CO(2)] on leaf area was generally small, but most dramatic under ample N
      conditions; this increased the stimulation of whole-season C(gain). These results
      suggest that a decrease in C(gain) enhancement following elevated CO(2) levels is
      difficult to avoid, but that careful management of nitrogen levels can alter the
      whole-season C(gain) enhancement.

PMID- 16608458
TI  - Season-long elevation of ozone concentration to projected 2050 levels under fully
      open-air conditions substantially decreases the growth and production of soybean.
AB  - Mean surface ozone concentration is predicted to increase 23% by 2050. Previous
      chamber studies of crops report large yield losses caused by elevation of
      tropospheric ozone, and have been the basis for projecting economic loss. This is
      the first study with a food crop (soybean, Glycine max) using free-air gas
      concentration enrichment (FACE) technology for ozone fumigation. A 23% increase
      in ozone concentration from an average daytime ambient 56 p.p.b. to a treatment
      69 p.p.b. over two growing seasons decreased seed yield by 20%. Total above
      ground net primary production decreased by 17% without altering dry mass
      allocation among shoot organs, except seed. Fewer live leaves and decreased
      photosynthesis in late grain filling appear to drive the ozone-induced losses in
      production and yield. These results validate previous chamber studies suggesting
      that soybean yields will decrease under increasing ozone exposure. In fact, these
      results suggest that when treated under open-air conditions yield losses may be
      even greater than the large losses already reported in earlier chamber studies.
      Yield losses with elevated ozone were greater in the second year following a
      severe hailstorm, suggesting that losses caused by ozone might be exacerbated by
      extreme climatic events.

PMID- 16608459
TI  - Elevated CO(2) and elevated temperature have no effect on Douglas-fir fine-root
      dynamics in nitrogen-poor soil.
AB  - Here, we investigate fine-root production, mortality and standing crop of Douglas
      fir (Pseudotsuga menziesii) seedlings exposed to elevated atmospheric CO(2) and
      elevated air temperature. We hypothesized that these treatments would increase
      fine-root production, but that mortality would be greater under elevated
      temperature, leading to a smaller increase in standing crop. Seedlings were grown
      in outdoor, sun-lit controlled-environment chambers containing native soil. They
      were exposed in a factorial design to two levels of atmospheric CO(2) and two
      levels of air temperature. Minirhizotron methods were used to measure fine-root
      length production, mortality and standing crop every 4 wk for 36 months. Neither
      elevated atmospheric CO(2) nor elevated air temperature affected fine-root
      production, mortality, or standing crop. Fine roots appeared to root deeper in
      the soil profile under elevated CO(2) and elevated temperature. Low soil nitrogen
      (N) levels apparently limited root responses to the treatments. This suggests
      that forests on nutrient-poor soils may exhibit limited fine-root responses to
      elevated atmospheric CO(2) and elevated air temperature.

PMID- 16608460
TI  - Suites of root traits differ between annual and perennial species growing in the
      field.
AB  - Here, we tested whether root traits associated with resource acquisition and
      conservation differed between life histories (annuals, perennials) and families
      (Fabaceae, Asteraceae and Poaceae). Root topology, morphology, chemistry and
      mycorrhizal colonization were measured on whole root systems of 18 field-grown
      herbaceous species grown and harvested in central Argentina. Annuals differed
      from perennials in several root traits important in resource uptake and
      conservation. They exhibited higher specific root length (SRL), root nitrogen
      concentration (RNC) and mycorrhizal colonization but had lower root tissue
      density (RTD) than perennials. They did not differ in topology or construction
      cost. These differences were consistent among families. Families differed only in
      a few root traits known to be strongly associated with certain lineages such as
      topology and nitrogen concentration. There was a strong parallel between root
      traits and analogous leaf traits described in the literature for annuals and
      perennials. Our results suggest the existence at the root level of an acquisitive
      vs conservative syndrome consistent among families similar to that previously
      reported for above-ground traits.

PMID- 16608461
TI  - Arbuscular mycorrhizal fungi associated with Populus-Salix stands in a semiarid
      riparian ecosystem.
AB  - This study examined the activity, species richness, and species composition of
      the arbuscular mycorrhizal fungal (AMF) community of Populus-Salix stands on the
      Verde River (Arizona, USA), quantified patterns of AMF richness and colonization
      along complex floodplain gradients, and identified environmental variables
      responsible for structuring the AMF community. Samples from 61 Populus-Salix
      stands were analyzed for AMF and herbaceous composition, AMF colonization,
      gravimetric soil moisture, soil texture, per cent organic matter, pH, and
      concentrations of nitrate, bicarbonate phosphorus and exchangeable potassium. AMF
      species richness declined with stand age and distance from and elevation above
      the channel and was positively related to perennial species cover and richness
      and gravimetric soil moisture. Distance from and elevation above the active
      channel, forest age, annual species cover, perennial species richness, and
      exchangeable potassium concentration all played a role in structuring the AMF
      community in this riparian area. Most AMF species were found across a wide range
      of soil conditions, but a subset of species tended to occur more often in hydric
      areas. This group of riparian affiliate AMF species includes several not
      previously encountered in the surrounding Sonoran desert.

PMID- 16608462
TI  - Fine-scale distribution of pine ectomycorrhizas and their extramatrical mycelium.
AB  - In order to clarify the functional role of individual ectomycorrhizal (EcM)
      fungal species in the field, we need to relate their abundance and distribution
      as mycorrhizas to their abundance and distribution as extramatrical mycelium
      (EMM). We divided each of four 20 cm x 20 cm x 2 cm slices of pine forest soil
      into 100 cubes of 2 cm x 2 cm. For each cube, ectomycorrhizas were identified and
      the presence of EMM of the EcM fungi recorded as ectomycorrhizas was determined
      by terminal restriction fragment length polymorphism (T-RFLP) analysis of ITS
      rDNA. Ectomycorrhizas and EMM of seven EcM species were mapped. Spatial
      segregation of mycorrhizas and EMM was evident and some species produced their
      EMM in different soil layers from their mycorrhizas. The spatial relationship
      between mycorrhizas and their EMM generally conformed to their reported
      exploration types, but EMM of smooth types (e.g. Lactarius rufus) was more
      frequent than expected. Different EcM fungi foraged at different spatial scales.

PMID- 16608463
TI  - The auxin-inducible GH3 homologue Pp-GH3.16 is downregulated in Pinus pinaster
      root systems on ectomycorrhizal symbiosis establishment.
AB  - In an attempt to determine whether auxin-regulated plant genes play a role in
      ectomycorrhizal symbiosis establishment, we screened a Pinus pinaster root cDNA
      library for auxin-upregulated genes. This allowed the identification of a cDNA,
      Pp-GH3.16, which encodes a polypeptide sharing extensive homologies with GH3
      proteins of different plants. Pp-GH3.16 was specifically upregulated by auxins
      and was not affected by cytokinin, gibberellin, abscisic acid or ethylene, or by
      heat shock, water stress or anoxia. Pp-GH3.16 mRNAs were quantified in pine roots
      inoculated with two ectomycorrhizal fungi, Hebeloma cylindrosporum and Rhizopogon
      roseolus. Surprisingly, Pp-GH3.16 was downregulated following inoculation with
      both fungal species. The downregulation was most rapid on establishment of
      symbiosis with an indole-3-acetic acid (IAA)-overproducing mutant of H.
      cylindrosporum, which overproduced mycorrhizas characterized by a hypertrophic
      Hartig net. This indicates that, despite being auxin-inducible, Pp-GH3.16 can be
      downregulated on establishment of symbiosis with a fungus that releases auxin. By
      contrast, Pp-GH3.16 was not downregulated in pine root systems inoculated with a
      nonmycorrhizal mutant of H. cylindrosporum, suggesting that the downregulation we
      observed in mycorrhizal root systems was a component of the molecular cross-talk
      between symbiotic partners at the origin of differentiation of symbiotic
      structures.

PMID- 16608464
TI  - Peptide uptake in the ectomycorrhizal fungus Hebeloma cylindrosporum:
      characterization of two di- and tripeptide transporters (HcPTR2A and B).
AB  - Constraints on plant growth imposed by low availability of nitrogen are a
      characteristic feature of ecosystems dominated by ectomycorrhizal plants.
      Ectomycorrhizal fungi play a key role in the N nutrition of plants, allowing
      their host plants to access decomposition products of dead plant and animal
      materials. Ectomycorrhizal plants are thus able to compensate for the low
      availability of inorganic N in forest ecosystems. The capacity to take up
      peptides, as well as the transport mechanisms involved, were analysed in the
      ectomycorrhizal fungus Hebeloma cylindrosporum. The present study demonstrated
      that H. cylindrosporum mycelium was able to take up di- and tripeptides and use
      them as sole N source. Two peptide transporters (HcPTR2A and B) were isolated by
      yeast functional complementation using an H. cylindrosporum cDNA library, and
      were shown to mediate dipeptide uptake. Uptake capacities and expression
      regulation of both genes were analysed, indicating that HcPTR2A was involved in
      the high-efficiency peptide uptake under conditions of limited N availability,
      whereas HcPTR2B was expressed constitutively.

PMID- 16608466
TI  - In defence of inpatient nurses: lessons from Enron for the NHS.

PMID- 16608465
TI  - Phylogenetic relationships in Elymus (Poaceae: Triticeae) based on the nuclear
      ribosomal internal transcribed spacer and chloroplast trnL-F sequences.
AB  - To estimate the phylogenetic relationship of polyploid Elymus in Triticeae,
      nuclear ribosomal internal transcribed spacer (ITS) and chloroplast trnL-F
      sequences of 45 Elymus accessions containing various genomes were analysed with
      those of five Pseudoroegneria (St), two Hordeum (H), three Agropyron (P) and two
      Australopyrum (W) accessions. The ITS sequences revealed a close phylogenetic
      relationship between the polyploid Elymus and species from the other genera. The
      ITS and trnL-F trees indicated considerable differentiation of the StY genome
      species. The trnL-F sequences revealed an especially close relationship of
      Pseudoroegneria to all Elymus species included. Both the ITS and trnL-F trees
      suggested multiple origins and recurrent hybridization of Elymus species. The
      results suggested that: the St, H, P, and W genomes in polyploid Elymus were
      donated by Pseudoroegneria, Hordeum, Agropyron and Australopyrum, respectively,
      and the St and Y genomes may have originated from the same ancestor;
      Pseudoroegneria was the maternal donor of the polyploid Elymus; and some Elymus
      species showed multiple origin and experienced recurrent hybridization.

PMID- 16608467
TI  - Supplementary prescribing: potential ways to reform hospital psychiatric care.
AB  - The objective of this study was to explore perceptions held by nurses and
      psychiatrists towards the potential application of supplementary prescribing on
      acute psychiatric wards. Six focus groups were conducted with 19 nurses and seven
      psychiatrists who worked on three wards. Two major themes were identified: first,
      ways in which patients could receive care and treatment through supplementary
      prescribing and in new forms of partnership and second, ways by which nurses and
      psychiatrists could be organized to deliver their care through a supplementary
      prescribing framework. Nurses and psychiatrists were generally positive about the
      advent of prescribing and offered positive views as to how patient care could be
      improved and a general willingness for nurses to adapt and work differently.
      Findings from this exploratory study offer practical solutions to how
      supplementary prescribing could work on acute psychiatric wards.

PMID- 16608468
TI  - Hospital-based industrial therapy units and the people who work within them - an
      Irish case analysis using a soft-systems approach.
AB  - Occupational training and employment is seen as a central concern in the delivery
      of community-orientated mental health services aimed at enhancing the quality of
      life of people with enduring mental illness. A range of schemes from sheltered to
      open employment now operates in a number of countries, with a concomitant growth
      of interest in their evaluation. At the same time, hospital-based workshops,
      often referred to as industrial therapy units (ITUs), have steadily declined
      because they are seen as outdated and less efficacious compared with community
      located training and employment. However, whether the total disappearance of the
      traditional ITU is a positive development may be open to question. This paper
      reports on a study of five mental health hospital-based sheltered workshops
      located in one Health Board area in Ireland, which catered for the needs of
      people with enduring mental health problems. Utilizing a soft-systems
      methodological approach, it examined their role and significance to 'users' who
      spent occupational time in them, the staff who worked in them and the clinicians
      who referred users to them.

PMID- 16608469
TI  - A qualitative analysis of the 'management of schizophrenia' within a medium
      secure service for men with learning disabilities.
AB  - Within secure psychiatric services, nurses trained to work with people with
      learning disabilities are often called upon to deal with those experiencing
      psychosis; a role that they are not routinely prepared for in generic learning
      disability nurse training. Psycho-social interventions (PSI) are recommended as
      an adjunct to routine pharmacological treatment for people experiencing
      psychosis. There is a small literature that suggests that PSI has utility with
      people with learning disabilities. As part of a wider evaluation of the
      introduction of a PSI framework to a 10-bedded medium-secure unit for men with
      learning disabilities and mental health problems, 13 members of nursing staff
      completed the 'Management of Schizophrenic Patients Checklist'. The responses
      were analysed using a grounded theory approach. Principle themes identified are
      described. The therapy vs. security quandary frequently reported in forensic
      psychiatry was evident in responses. The findings are guiding a programme of
      training and ongoing supervision within the service and are discussed in the
      context of wider therapeutic issues and institutional environment.

PMID- 16608470
TI  - Integration of a suicide risk assessment and intervention approach: the
      perspective of youth.
AB  - The process of suicide risk assessment is often a challenge for mental health
      nurses, especially when working with an adolescent population. Adolescents who
      are struggling with particular problems, stressors and life events may exhibit
      challenging and self-harm behaviour as a means of communication or a way of
      coping. Current literature provides limited exploration of the effects of loss,
      separation and divorce, blended families, conflict and abuse on child and
      adolescent development and the increased vulnerability of at-risk youth. There is
      also limited research that provides clear and practical models for the assessment
      and management of youth suicidal ideation and behaviour. This paper will discuss
      the integration of a number of theories to establish a comprehensive assessment
      of risk. The research study described the perspective of youth and their families
      who had experienced this particular model; however, this paper will discuss only
      the youth perspective. In order for this model to be successful, it is important
      for mental health nurses to make a connection with the youth and begin to
      understand the self-harm behaviour in context of the adolescents' family, and
      their social and school experiences. It also requires recognition that
      adolescents with challenging and self-harm behaviour are hurting and troubled
      adolescents with hurtful and troublesome behaviour.

PMID- 16608471
TI  - Preliminary outcomes of a trial to reduce conflict and containment on acute
      psychiatric wards: City Nurses.
AB  - Acute psychiatric wards experience high levels of conflict behaviours (violence,
      absconding, self-harm, rule breaking and medication refusal) by patients. These
      events cause stress and injury to staff and patients. Their management through
      containment methods (e.g. sedation, restraint, seclusion) is contentious, and
      nurses are ambivalent about their use. The aim of this study was to reduce
      conflict and containment on two acute psychiatric wards through changes in
      nurses' beliefs, attitudes and practices. Two 'City Nurses' were employed to work
      with two acute wards for 1 year, assisting with the implementation of changes
      according to a working model of conflict and containment generation, itself based
      on previous research. Evaluation was via before-and-after measures. Statistically
      and clinically significant decreases in conflict occurred, with falls in
      aggression, absconding and self-harm. Ward atmosphere improved and nurse-patient
      interaction rates increased. There was no significant change in containment
      method use. Significant reductions in aggression, absconding and self-harm can be
      achieved on acute psychiatric wards. However, it does not appear that containment
      can be reduced, even through large reductions in conflict.

PMID- 16608472
TI  - 'Let a hundred flowers blossom, let a hundred schools of thought contend': a case
      for therapeutic pluralism in mental health nursing.
AB  - With the dominance of cognitive behavioural therapies within mental health
      nursing educational and practice settings, a danger exists that a narrow
      application of therapy interventions and micro skills will result. Given the rich
      and diverse variations of presenting circumstances to community mental health
      services, an incorporation of therapy approaches beyond the cognitive behavioural
      model is essential. This paper initially aims to demonstrate the core values of
      mental health nursing as being at least partially incongruent with those of
      cognitive behavioural therapies. This paper also aims to provide brief examples
      of the use of alternate evidential practice-based therapies more reflective of
      mental health nursing values across a spectrum of community mental health service
      where the authors are employed.

PMID- 16608473
TI  - Becoming one person: living with dissociative identity disorder.
AB  - Dissociative identity disorder is a rare diagnosis, although people currently
      with a diagnosis of psychosis may in fact be experiencing what is associated with
      the disorder. This article is co-authored by a nurse and a person who has lived
      with alters (multiple personalities) for nearly all of her life. Because of the
      rarity of the diagnosis, there is much misunderstanding and ignorance among lay
      people and mental health professionals. This article therefore clarifies
      historical and contemporary issues surrounding this particular mental health
      problem both through examining the literature and through narrative of the
      person's experience. Special attention is given to the reality of coping with the
      difficulties that dissociative identity disorder create.

PMID- 16608474
TI  - The effects of a non-smoking policy on nursing staff smoking behaviour and
      attitudes in a psychiatric hospital.
AB  - The UK Department of Health required that by April 2001, all NHS bodies would
      have implemented a smoking policy. It has been suggested that the best
      demonstration a hospital can make of its commitment to health is to ban smoking
      on its premises. This paper reports on an evaluation of the effectiveness of a
      non-smoking policy in a newly opened NHS psychiatric hospital. Questionnaires
      were sent to all 156 nursing staff in a psychiatric hospital to assess the
      effectiveness of the policy in terms of staff smoking behaviour, attitudes to the
      restriction and compliance with the policy. Of the 156 questionnaires
      distributed, 92 (58%) were returned; smokers, former smokers and those who have
      never smoked were quite evenly represented at 34.78%, 34.78% and 30.43%,
      respectively. Of eight critical success factors for the policy, only one, staff
      not smoking in Trust public areas, had been achieved. A non-smoking policy was
      generally accepted as necessary by nursing staff working in a mental health
      setting. Staff felt that the policy was not effective in motivating smoking
      nurses to stop and that insufficient support was given to these nurses. The study
      highlights the importance of introducing staff support systems as an integral
      part of smoking policies and the role of counterintuitive behaviour in the
      effectiveness of smoking policy introduction in healthcare settings.

PMID- 16608475
TI  - The effect of a training course on mental health nurses' attitudes on the reasons
      of patient aggression and its management.
AB  - Aggression in healthcare systems poses a major problem for nurses because they
      are the most susceptible to suffer violence. Studies demonstrate that attitudes
      of nurses influence their behaviour regarding aggression and violence. Training
      programmes can positively change nurses' attitudes. This quasi-experimental study
      aimed to examine the effects of a systematic training course in aggression
      management on mental health nurses' attitudes about the reasons for patients'
      aggression and on its management. Sixty-three nurses (29 in the intervention and
      34 in the control group) participated in this quasi-experimental pre-test and
      post-test study. The attitude of the participants of a training course was
      recorded by the German version of the Management of Aggression and Violence
      Attitude Scale (MAVAS). No significant attitude changes occurred in the
      intervention group at post-test. It is concluded that trainings intending to
      influence attitudes regarding the reason for patient aggression should consider
      the impact of the pedagogical quality of the training course, organizational
      support, and the user's perception. Moreover, it remains questionable to what
      extent a single instrument of measurement can record attitude changes.

PMID- 16608477
TI  - Informal care as relationship: the case of the Magnificent Seven.
AB  - Continual and/or repetitive informal caring and the part childhood, developmental
      and socially constructed identity play roles in adult informal care, form the
      background to the questions of why individuals gravitate toward such
      relationships and why they often continue to care in the face of overwhelming
      obstacles. A synthesis of the literature is presented, leading to personal
      histories as a method of discovery. The Biographic Narrative Interpretive
      Method's minimalist interview technique is put forth as the key data-gathering
      event. Reflecting teams, underpinned by hermeneutics or interpretive
      phenomenology, are used for the analyses. Data from in-depth, biographic
      interviews with two informal carers (a mother and her adult son) from a seven
      member, three-generational family are presented. The study reveals that this
      family defines disability as a status that they share in common: disability
      demonstrates relationships and keeps the family together, but discourages
      mobility. It is suggested that often-unmet childhood needs propelled these
      particular individuals into demonstrating those needs as adults by assuming
      informal care relationships. The case is made that their biographies impact upon
      their management of health and enduring illnesses within caring roles. Further
      biographic research within the caring profession is recommended.

PMID- 16608476
TI  - Functional status and quality of life in patients with first-episode major
      depression.
AB  - The aim of this study was to analyse the level of severity of major depression
      and its relation to functioning and health-related quality of life over time in
      patients treated for their first episode of major depression. Thirty-three adult
      patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-IV) criteria for major depression were included in the study. Semi
      structured interviews and self-assessment questionnaires were used at baseline
      and at 6-monthly intervals in a 2-year follow-up, in order to measure the level
      of severity of depression, functioning and quality of life. The results showed
      that the first episode of major depression was rated as severe in 43% of cases.
      Multiple domains of functioning as well as quality of life were strongly affected
      in patients at baseline, although the level of functioning increased
      significantly over the study period, as did quality of life, but not concurrently
      with the decrease in the level of severity of the depression. Psychosocial
      functioning is an important outcome measure related to major depression, which
      underlines the importance of separate evaluations initiated and conducted by
      mental health nurses in order to determine whether or not patients have actually
      achieved a state of health.

PMID- 16608478
TI  - The Self-Injury Questionnaire: evaluation of the psychometric properties in a
      clinical population.
AB  - This paper presents the findings, from a clinical study, on the reliability and
      validity of a new measure for intentions in self-harm behaviour, the Self-Injury
      Questionnaire (SIQ). Eighty-three patients, who had presented to an emergency
      department with an episode of self-harm/suicidal behaviour, were given the SIQ as
      part of a battery of measures to evaluate differentiation in self-harm intentions
      based upon a history of childhood physical and/or sexual abuse. The internal
      consistency for the total scale was strong (alpha = 0.83). Construct validity
      demonstrated significant correlations with standardized measures. A principle
      component analysis of responses yielded a five-factor solution with 'affect
      regulation' items loading on the first factor. Cronbach's alphas were adequate
      for each subscale (alpha = 0.72-0.77). These preliminary findings indicate that
      the SIQ is a valid and reliable measure for research in an acute self-harming
      population.

PMID- 16608479
TI  - Clinical governance in practice: closing the loop with integrated audit systems.
AB  - Clinical governance has been acknowledged as the driving force behind National
      Health Service (NHS) reform since the government white paper outlined a new style
      of NHS in the UK in 1997. The framework of clinical governance ensures that NHS
      organizations are accountable for continually improving the quality of their
      services and safeguarding high standards of care by creating an environment in
      which excellence in clinical care will develop. A major component of a clinical
      governance framework requires utilizing audit procedures, which assess the
      effectiveness of current systems and ultimately direct continual quality
      improvement. This paper describes the audit component of a local clinical
      governance framework designed for a unit based within an NHS trust, which has
      utilized a multidisciplinary approach to assess the effectiveness of a newly
      commissioned service and its impact on the residents and staff. The unit is a 12
      bedded, low-secure-intensive rehabilitation unit for clients with severe and
      enduring mental illness. Using recognized and standardized psychometric outcome
      measures, information was collected on clinical symptoms, social functioning,
      social behaviour, quality of life, relationship quality with named nurses and
      medication side-effects. Additionally, confidential staff measures were included
      to assess levels of burnout, identify expressed emotion and assess staff
      perception of models of illness. The paper includes a comprehensive account of
      how managerial commitment, teaching processes and application of technology
      ensured prompt data collection and maintained the momentum through the audit
      timescale. Data analysis and presentation of data in both clinical reviews and in
      senior management meetings within the unit are discussed. Findings highlight the
      full integration of the audit system into the processes of the unit. Clinically,
      the paper highlights the enhancement of the knowledge base of the client group
      and the influence on clinical decision-making processes and care delivery as a
      result of the audit. Brief clinical examples are given. In conclusion, the impact
      of the audit on unit strategy and organizational efficiency are discussed to
      highlight the importance of closing the audit loop and completing the cycle of
      clinical governance. The audit system has positive implications for replication
      in other services.

PMID- 16608480
TI  - Cognitive behaviour therapy and people with learning disabilities: implications
      for developing nursing practice.
AB  - People with learning disabilities are an ageing and increasing population and
      have been the subject of policy initiatives by the four countries of the UK,
      detailing the range of supports that need to be in place for this group. The
      evidence base of their mental health needs is growing and with it the need to
      ensure the full range of psychotherapies available to the general population are
      made available to people with learning disabilities. Cognitive Behaviour Therapy
      (CBT) is now a widely accepted and effective form of psychotherapy for many
      mental health problems and the evidence base is growing on the effectiveness with
      the learning disability population; however, the model needs to be applied
      differently for this group to take account of their cognitive impairment and
      support needs. Registered Nurses in Learning Disabilities are well placed to
      apply this approach within their clinical practice; however, there is an absence
      of leadership and direction in the development of CBT for this group of
      clinicians. There is a need to support education and practice development to
      contribute to addressing the emotional needs of people with learning
      disabilities. Action is required to support education to prepare Registered
      Nurses in Learning Disabilities to practice CBT and to contribute to the ongoing
      development of research in this area of clinical practice.

PMID- 16608481
TI  - Sisyphus happy: the experience of depression.
AB  - Depression has been well documented, in the academic sense. This paper offers one
      person's experience of periods of depression. It describes symptoms and personal
      ideas about this commonly experienced condition. It raises questions about the
      legitimacy of psychiatric and psychological theorizing, and draws from various
      existential positions to support the text. The author suggests that depression is
      not, particularly a 'learning experience' and, far less, a form of personal
      growth.

PMID- 16608482
TI  - The trials and tribulations of performing within the research arena.

PMID- 16608485
TI  - Comparison of plume structures of carbon dioxide emitted from different mosquito
      traps.
AB  - A large field wind tunnel was used to compare four types of CO2-baited mosquito
      traps. This study compared the plume structure and concentration of CO2 emitted
      by each trap, flow of suction into the trapping systems, flow of CO2 being
      released, trap shape and configuration, differences in visual appearance, and
      differences in temperature and humidity of emissions at the source of CO2
      compared to ambient air. The structure of the CO2 plumes emitted by each trap
      differed considerably. All four plumes were turbulent, causing the concentration
      of CO2 within several metres of the source to attenuate to between 375 and 875
      p.p.m. The Encephalitis Virus Surveillance (EVS) trap emitted concentrations of
      CO2 exceeding 20,000 p.p.m., the detection limits of our equipment, whereas the
      Mosquito Magnet Freedom (MMF), Mosquito Magnet Liberty (MML) and Mosquito Magnet
      X (MMX) traps released CO2 at peaks of about 3500, 7200 and 8700 p.p.m.,
      respectively. The MMX trap produced the greatest air velocity at both the suction
      inlet and CO2 outlet, followed by the MMF, MML and the EVS traps, respectively.

PMID- 16608486
TI  - Orientation of Culex mosquitoes to carbon dioxide-baited traps: flight manoeuvres
      and trapping efficiency.
AB  - Females of Culex quinquefasciatus Say and Culex tarsalis Coquillet (Diptera:
      Culicidae) in the host-seeking stage were released and video recorded in three
      dimensions in a large field wind tunnel as they flew to four kinds of CO2-baited
      mosquito traps. The trapping efficiency (number of mosquitoes approaching
      compared to the number caught) was determined for each trap type. The
      Encephalitis Virus Surveillance (EVS), Mosquito Magnet Freedom (MMF) and Mosquito
      Magnet Liberty (MML) traps captured only 13-16% of approaching Cx.
      quinquefasciatus females, whereas the Mosquito Magnet-X (MMX) trap captured 58%.
      Similar results were obtained for Cx. tarsalis. Orientation behaviour and flight
      parameters of mosquitoes approaching the four traps were compared. Mosquitoes
      spent the most time orienting to the EVS trap. Flight speed decreased as
      mosquitoes entered the vicinity of each trap and a large portion of their time
      was spent within 30 cm downwind of the traps. Flights became highly tortuous
      downwind of the poorly performing traps and just upwind of the MMX trap.
      Differences between traps and possible explanations for the superior performance
      of the MMX trap are considered.

PMID- 16608487
TI  - Co-occurrence of East and West African kdr mutations suggests high levels of
      resistance to pyrethroid insecticides in Anopheles gambiae from Libreville,
      Gabon.
AB  - Point mutations in the voltage-gated sodium channel gene involved in knockdown
      resistance to DDT and pyrethroid insecticides have been described in several
      insect species. In the malaria vector Anopheles gambiae Giles sensu stricto
      (Diptera: Culicidae) two mutations have been identified. The first, consisting of
      a leucine-phenylalanine substitution at amino acid position 1014, is widespread
      in West Africa. The second, a leucine-serine substitution at the same position,
      has to date only been detected in western Kenya. Analysis of the kdr polymorphism
      in a sample of 106 An. gambiae s.s. of the rDNA S-form/Type I collected in
      Libreville (Gabon) surprisingly revealed the presence of both East and West
      African kdr mutations with frequencies of 63% and 37%, respectively. No wild-type
      alleles were detected and there was an excess of heterozygous genotypes (P =
      0.04). In addition, an inconsistency was found during the kdr genotyping
      procedures by polymerase chain reaction, which could have lead to an
      underestimation of resistance alleles. The implications of these findings are
      discussed.

PMID- 16608488
TI  - Molecular variation, systematics and distribution of the Anopheles fluviatilis
      complex in southern Asia.
AB  - Species of the Anopheles fluviatilis James and Anopheles minimus complexes
      (Diptera: Culicidae) are difficult to distinguish morphologically. Members of the
      two complexes have been confused and, consequently, their distributions and roles
      in malaria transmission are uncertain. We identified numerous mosquitoes from
      China, Thailand, Vietnam, India, Nepal, Pakistan and Iran by single-strand
      conformation polymorphism (SSCP) and/or sequencing, and analysed the variation in
      the 28S D3 region of ribosomal DNA for members of the Minimus Subgroup and also
      the internal transcribed spacer region 2 (ITS2) for members of the An.
      fluviatilis complex. The D3 region is highly conserved between taxa and therefore
      could serve as a standard for molecular diagnosis of the subgroup members. D3
      sequence, bionomics and malaria transmission data provide further evidence that
      An. fluviatilis S in India is conspecific with An. minimus C in South-east Asia.
      An. fluviatilis T has three ITS2 haplotypes (designated T1, T2 and Y) and its
      distribution in India, Nepal, Pakistan and Iran is confirmed. An. fluviatilis U
      is well defined on cytogenetic grounds in Uttar Pradesh, India, but is very close
      to An. fluviatilis T and the two species may hybridize in some regions. Variant
      ITS2 sequences suggest the possible existence of two additional taxa within the
      An. fluviatilis complex, one in Iran and another in India, provisionally
      designated An. fluviatilis forms V and X, respectively. The distributions of
      members of the An. fluviatilis and An. minimus complexes in south-central Asia
      are summarized.

PMID- 16608489
TI  - Molecular systematics of the Philippine malaria vector Anopheles flavirostris.
AB  - Allozyme and molecular sequence data from the malaria vector Anopheles
      flavirostris (Ludlow) (Diptera: Culicidae) were analysed from 34 sites throughout
      the Philippines, including the type locality, to test the hypothesis that this
      taxon is a single panmictic species. A finer-scaled allozyme study, of mainly
      Luzon samples, revealed no fixed genetic differences in sympatric sites and only
      low levels of variation. We obtained data from partial sequences for the internal
      transcribed spacer 2 (ITS2) (483 bp), the third domain (D3) (330 bp) of the 28S
      ribosomal DNA subunit and cytochrome c oxidase subunit I (COI) of mitochondrial
      DNA (261 bp). No sequence variation was observed for ITS2, only a one base pair
      difference was observed between Philippine and Indonesian D3 sequences and An.
      flavirostris sequences were unique, confirming their diagnostic value for this
      taxon. Sixteen COI haplotypes were identified, giving 25 parsimony informative
      sites. Neighbour-Joining, Maximum Parsimony, Maximum Likelihood and Bayesian
      phylogenetic analysis of COI sequences for An. flavirostris and outgroup taxa
      revealed strong branch support for the monophyly of An. flavirostris, thus
      confirming that Philippine populations of this taxon comprise a single separate
      species within the Minimus Subgroup of the Funestus Group. Variation in the
      behaviour of An. flavirostris is likely to be intraspecific rather than
      interspecific in origin.

PMID- 16608490
TI  - Superior reproductive success on human blood without sugar is not limited to
      highly anthropophilic mosquito species.
AB  - Anthropophilic mosquitoes such as Aedes aegypti L. (Diptera: Culicidae) have been
      shown to have superior reproductive success on human blood when sugar is not
      available. Life-table experiments were conducted with Aedes albopictus Skuse and
      Ae. aegypti to compare the effects of sugar availability on age-specific
      survivorship, lifetime and daily fecundity, and blood-feeding frequency when
      offered human blood daily. There were no significant interactions between the
      effects of sugar availability and mosquito species for these four variables,
      indicating similar effects of sugar availability for both species. Lifetime
      fecundity was not significantly affected by sugar availability, but sugar
      deprived females had significantly reduced age-specific survivorship than did
      sugar-fed females. In absence of sugar, females took bloodmeals twice as often,
      resulting in a higher daily fecundity. The results indicate that superior
      reproductive success on human blood without sugar does not seem to be limited to
      highly anthropophilic mosquito species, such as Ae. aegypti. We conclude that
      evolution of a highly anthropophilic feeding strategy is not an inevitable result
      of the ability to thrive on human blood alone.

PMID- 16608491
TI  - Guide to blackflies of the Simulium damnosum complex in eastern and southern
      Africa.
AB  - At least 26 members of the Simulium damnosum Theobald complex (Diptera:
      Simuliidae) are known from eastern Africa, most of which are assumed to be non
      anthropophilic and some are restricted to small areas of endemicity. Their
      discovery was based on polytene chromosome inversion polymorphisms and since then
      they have been cited as cytological entities, but, in many cases, with inadequate
      descriptions (e.g. without illustrations of the chromosomes). The present
      distribution, taxonomy and vector identity have been re-evaluated during the last
      decade in conjunction with ongoing onchocerciasis control programmes. Here, a
      summary of the relevant data is presented, integrating results of cytotaxonomic,
      morphotaxonomic and molecular investigations into a guide that provides a
      comprehensive system of identification for the cytoforms 'Kagera', 'Kasyabone',
      'Kibwezi', 'Kisiwani', 'Kisiwani E', 'Kulfo', 'Linthipe', 'Mombo', 'Mutonga',
      'Njombe', 'Nkusi', 'Nkusi SA', 'Nkusi SW', 'Nyika', 'Pienaars', 'Sanje', 'Sebwe',
      'Turiani', Simulium damnosum sensu stricto, Simulium kaffaense Hadis et al.,
      Simulium kilibanum Gouteux, Simulium kipengere Krueger, Simulium latipollex
      (Enderlein), Simulium pandanophilum Kruger, Nurmi & Garms, Simulium plumbeum
      Krueger, Simulium thyolense Vajime et al. and for five newly recognized molecular
      forms of 'Nkusi' and S. kilibanum. All taxa except S. pandanophilum are assigned
      to one of five subcomplexes (damnosum, Ketaketa, Kibwezi, Sanje, squamosum)
      within the S. damnosum complex. The guide encompasses anthropophilic and non
      anthropophilic segregates for the whole of eastern and southern Africa, and is
      not restricted to larval chromosome criteria; in many cases it also allows the
      typing of adult flies.

PMID- 16608492
TI  - Revision of the Ketaketa subcomplex of blackflies of the Simulium damnosum
      complex.
AB  - A revision of the taxonomy of the Ketaketa subcomplex of the Simulium damnosum
      Theobald complex (Diptera: Simuliidae) is presented including new material from
      Tanzania, Malawi and South Africa. The cytotaxonomy, morphology and molecular
      identity of known and new taxa are described. The Ketaketa subcomplex is
      cytotaxonomically defined by the paracentric inversion 1L-7. We recognize three
      sibling species, namely Simulium latipollex (Enderlein), Simulium plumbeum
      Krueger, sp.n. and Simulium kipengere Krueger, sp.n., the latter comprising three
      cytoforms: 'Typical', 'Linthipe' and 'Mombo'. The cytoforms 'Mwamphanzi',
      'Ketaketa' and 'Hammerkopi' are synonymized with S. plumbeum. Identification keys
      are provided on the basis of chromosomal and morphological characters. In view of
      their potential role as vectors of human onchocerciasis (river blindness) we also
      discuss the possible medical importance of the different cytoforms and their
      geographical distribution.

PMID- 16608493
TI  - Transmission of Onchocerca volvulus and prospects for the elimination of its
      vector, the blackfly Simulium neavei in the Mpamba-Nkusi focus in Western Uganda.
AB  - The transmission of Onchocerca volvulus Leuckart (Spirudida: Onchocercidae) and
      the prospects of Simulium neavei Roubaud (Diptera: Simuliidae) vector elimination
      through ground larviciding were investigated in the Mpamba-Nkusi focus, western
      Uganda. Transmission levels and the initiated vector elimination activities were
      assessed to supplement the ongoing ivermectin mass distribution programme.
      Searches for breeding sites, adult fly catches, dissection of flies, river
      treatment with temephos (Abate) and a review of annual ivermectin treatment data
      were conducted. High levels of crab infestation with S. neavei sensu stricto
      immature stages were recorded; 57.9% and 100% for the Mpamba and Nyabugando river
      systems, respectively. The mean numbers of larvae/pupae per crab were 3.6 +/- 0.5
      in the Mpamba and 20.6 +/- 1.8 in the Nyabugando systems. Pre-intervention mean
      biting densities were 39 and 32 flies/(man day) in 2001 and 2002, respectively,
      and an annual biting rate in 2001 of > 14 000. The bimodal biting pattern of S.
      neavei s.s. consisted of two peaks; one in the morning (09.00-10.00 hours) and
      one in the afternoon (14.00-15.00 hours) with a mid-day lull in biting. The
      infection/infective rates were 13.3%/2.8% and 16.6%/2.9% in the dissected parous
      flies from the Mpamba and Nyabugando river systems, respectively. Out of
      approximately 1000 parous flies, 129 and 109 were found to be harbouring
      infective larvae of Onchocerca volvulus in their heads from the Mpamba and
      Nyabugando river systems, respectively. In spite of the > 10 years of ivermectin
      treatment, at a mean coverage of 71.3%, infection remained relatively high.
      Ground larviciding with temephos (Abate) initiated in June and October 2002 had a
      significant impact. In the Mpamba river system there was a significant (P <
      0.001) reduction in positive crabs from 57.9% in 2001 to 0.06% in 2003 and a
      decrease in the mean number of larvae/pupae per crab from 3.6 +/- 0.5 in 2001 to
      0.0007 +/- 0.0001 (P < 0.002) in 2003. Similarly, in the Nyabugando river system,
      a significant (P < 0.001) reduction in crab infestation from 100% in 2001 to
      0.06% in 2003 and a decrease in the mean number of larvae/pupae per crab from
      20.6 +/- 1.8 in 2001 to 0.06 +/- 0.03 in 2003. Drastic reductions were observed
      in the mean number of biting flies from 3 flies/h in 2001 to 0 flies/h in 2003
      and the annual biting rates fell from 14,235 flies/year in 2001 to only 730
      flies/year in 2003. These data suggest that substantial progress towards the goal
      of S. neavei s.s. vector elimination has been made and this will enhance the
      ongoing ivermectin treatment in this isolated focus.

PMID- 16608494
TI  - In vitro tests for evaluation of the hatchability of the eggs of Psoroptes mites
      following exposure to acaricidal compounds.
AB  - Three in vitro assays for the evaluation of the hatchability of the eggs of the
      mite Psoroptes ovis (Hering) (Acari: Psoroptidae) are described. Preliminary
      trials showed that hatching occurs at very high rates when eggs are incubated
      under conditions of high humidity, on a liquid medium and in agarose dishes.
      These three protocols were compared, taking into account the ease of preparation,
      follow-up and accuracy of counting. The best protocol was found to be the use of
      agarose dishes. It was accurate, easy to carry out and reproducible for further
      evaluation of existing or potentially new compounds against both adults and eggs
      of Psoroptes spp. The acaricidal properties of phoxim and amitraz were then
      evaluated against eggs and adults using the three protocols. Results showed that
      for both drugs, in vitro adulticidal activity was complete, whereas the in vitro
      ovicidal activity was only partial. Nevertheless, efficacy of amitraz against
      both adults and eggs was shown to be higher than that of phoxim.

PMID- 16608495
TI  - Larval growth rates of the blowfly, Calliphora vicina, over a range of
      temperatures.
AB  - Blowfly larvae (Diptera: Calliphoridae) fulfil an important ecological function
      in the decomposition of animal remains. They are also used extensively in
      forensic entomology, predominantly to establish a minimum time since death, or a
      minimum post-mortem interval, using the larval length as a 'biological clock'.
      This study examined the larval growth rate of a forensically important fly
      species, Calliphora vicina Robineau-Desvoidy (Diptera: Calliphoridae) at
      temperatures of between 4 degrees C and 30 degrees C, under controlled laboratory
      conditions. The laboratory flies had been trapped initially in London, U.K. The
      minimum developmental temperature was estimated to be 1 degrees C and 4700
      accumulated degree hours (ADH) were required for development from egg hatch to
      the point of pupariation. Lines fitted to the laboratory larval growth data were
      found to adequately explain the growth of larvae in the field. The nature of
      variation in growth rates from geographically isolated populations is discussed.

PMID- 16608496
TI  - Role of bacteria in the oviposition behaviour and larval development of stable
      flies.
AB  - Stable flies, Stomoxys calcitrans (L.), are the most important pests of cattle in
      the United States. However, adequate management strategies for stable flies,
      especially for pastured cattle, are lacking. Microbial/symbiont-based approaches
      offer novel venues for management of insect pests and/or vector-borne human and
      animal pathogens. Unfortunately, the fundamental knowledge of stable fly
      microbial associations and their effect on stable fly biology is lacking. In this
      study, stable flies laid greater numbers of eggs on a substrate with an active
      microbial community (> 95% of total eggs oviposited) than on a sterilized
      substrate. In addition, stable fly larvae could not develop in a sterilized
      natural or artificial substrate/medium. Bacteria were isolated and identified
      from a natural stable fly oviposition/developmental habitat and their individual
      effect on stable fly oviposition response and larval development was evaluated in
      laboratory bioassays. Of nine bacterial strains evaluated in the oviposition
      bioassays, Citrobacter freundii stimulated oviposition to the greatest extent. C.
      freundii also sustained stable fly development, but to a lesser degree than
      Serratia fanticola. Serratia marcescens and Aeromonas spp. neither stimulated
      oviposition nor supported stable fly development. These results demonstrate a
      stable fly bacterial symbiosis; stable fly larval development depends on a live
      microbial community in the natural habitat, and stable fly females are capable of
      selecting an oviposition site based on the microbially derived stimuli that
      indicate the suitability of the substrate for larval development. This study
      shows a promising starting point for exploiting stable fly-bacterial associations
      for development of novel approaches for stable fly management.

PMID- 16608497
TI  - Behavioural responses of dairy cattle to the stable fly, Stomoxys calcitrans, in
      an open field environment.
AB  - Individual cows (25 in each of four herds) were monitored 8-10 times weekly for
      12 weeks (stable fly season) on a southern California dairy, with 100
      observations per cow. The numbers of biting stable flies, Stomoxys calcitrans
      (L.) (Diptera: Muscidae) on the front legs and the frequencies of four fly
      repelling behaviours per 2-min observation period [head throws, front leg stamps,
      skin twitches (panniculus reflex) and tail flicks] were recorded. Fly numbers
      varied, peaking at 3.0-3.5 flies per leg in week 9 (late May). Weekly herd mean
      frequencies of fly-repelling behaviours were highly dependent on fly numbers,
      with a linear regression r(2) > 0.8. Head throws and stamps were less frequent
      than skin twitches and tail flicks. Individual cows differed in numbers of stable
      flies and behaviours. Behaviours were correlated with flies for individual cows,
      but at a lower level than were herd means (r = 0.3-0.7). Cows that stamped more
      within a herd tended to have lower fly counts; other fly-repelling behaviours
      were less effective. Cows maintained ranks within a herd with regard to fly
      numbers (r = 0.47), head throws (0.48), leg stamps (0.64), skin twitches (0.69)
      and tail flicks (0.64). Older cows tended to harbour higher fly numbers and to
      stamp less relative to younger adult cows. Ratios of leg stamps and head throws
      to fly numbers dropped significantly through time, suggesting habituation to pain
      associated with fly biting. Tail flicks were not effective for repelling
      Stomoxys, but were easiest to quantify and may help in monitoring pest intensity.
      At this low-moderate fly pressure, no consistent impacts on milk yield were
      detected, but methods incorporating cow behaviour are recommended for future
      studies of economic impact.

PMID- 16608498
TI  - Microgeographical breeding structure of the tsetse fly, Glossina pallidipes in
      south-western Kenya.
AB  - The origins of extant Glossina pallidipes Austen (Diptera: Glossinidae)
      populations in the ecologically well-studied Lambwe and Nguruman valleys in Kenya
      are controversial because populations have recovered after seemingly effective
      attempts to achieve high levels of control. The microgeographical breeding
      structure of the tsetse fly, G. pallidipes, was investigated by analysing spatial
      and temporal variation at eight microsatellite loci to test hypotheses about
      endemism and immigration. Samples were obtained at seasonal intervals from trap
      sites separated by 200 m to 14 km and arranged into blocks. G. pallidipes
      populations nearest to Lambwe and Nguruman also were sampled. Spatial analysis
      indicated that genetic differentiation by genetic drift was much less among
      trapping sites within Lambwe and Nguruman (F(ST) < or = 0.049) than between them
      (F(ST) = 0.232). F(ST) between Serengeti and Nguruman was 0.16 and F(ST) between
      Kodera Forest and Lambwe was 0.15. The genetic variance in G. pallidipes
      explained by dry and wet seasons (0.33%) was about one-fifth the variance among
      collection dates (1.6%), thereby indicating reasonable temporal stability of
      genetic variation. Gene frequencies in Kodera and Serengeti differed greatly from
      Lambwe and Nguruman, thereby falsifying the hypothesis that Lambwe and Nguruman
      were repopulated by immigrants. Harmonic mean effective (= breeding) population
      sizes were 180 in Lambwe and 551 in Nguruman. The genetic data suggest that G.
      pallidipes in Lambwe and Nguruman have been endemic for long intervals.

PMID- 16608499
TI  - First record and establishment of the mosquito Aedes albopictus in Spain.
AB  - The invasive mosquito Aedes (Stegomyia) albopictus (Skuse) (Diptera: Culicidae)
      was detected for the first time in Spain, in Sant Cugat del Valles, a city in the
      north-east of the country (41 degrees 28' N, 2 degrees 4' E, altitude 120 m),
      during August 2004. A male and one larva were collected in the backyard of a
      house and in a tree hole, respectively. Dense populations of adults and larvae
      were found in subsequent surveys, confirming the establishment of the species in
      the area. This is the first report of the establishment of this species in the
      Iberian Peninsula.

PMID- 16608500
TI  - Anopheles culicifacies sibling species B and E in Sri Lanka differ in longevity
      and in their susceptibility to malaria parasite infection and common
      insecticides.
AB  - Members of the Anopheles culicifacies Giles complex (Diptera: Culicidae) are well
      established as the predominant vectors of malaria in Sri Lanka. Until recently,
      only sibling species B was reported to be present in Sri Lanka, which was
      surprising as species B is a poor vector of malaria in India. This was clarified
      by the identification through Y-chromosome morphology that what was reported as B
      on the island is really a mixture of B and E. The fecundity, longevity and
      insecticide resistance of B and E are of relevance to malaria transmission and
      its control and are reported in this study. The mean egg production of these two
      sibling species did not differ significantly. The mean age of wild mosquitoes was
      assessed by the Polovodova technique of observing ovarian dilatations. More of
      species E than B had three or more dilatations, i.e. had reached an age at which
      sporozoites could have developed to maturity, although the difference between the
      species was of borderline significance. Following feeding on Plasmodium vivax or
      Plasmodium falciparum infected blood, some females of species E developed oocysts
      but none of species B did so. Both sibling species were found fully susceptible
      in laboratory tests to lambdacyhalothrin and deltamethrin, but resistant to DDT
      and partially resistant to malathion.

PMID- 16608501
TI  - Liver iron content assessment by routine and simple magnetic resonance imaging
      procedure in highly transfused patients.
AB  - BACKGROUND: Liver iron content (LIC) assessment by magnetic resonance imaging
      (MRI) is validated but not standardized. In a single center, we tried to assess
      the accuracy of a specific, simple MRI procedure adapted to high LIC from a well
      established simple and routine procedure known to quantify LIC. METHODS: In 27
      cases of monthly transfused patients, we compared biochemical values of LIC
      assessed on liver biopsy specimens and results obtained by two signal intensity
      ratio of gradient echo imaging (R2*) MRI protocols. The first was Gandon's
      routine procedure previously validated in liver disease and the second, our own
      method, was an addition of a gradient echo sequence specifically adapted to high
      LIC encountered in hematology practice. RESULTS: Twenty-seven liver biopsies were
      performed in 18 adult patients (myelodysplastic syndrome = 5, beta-thalassemia =
      13). LIC by biopsy ranged from 1.4 to 54 mg/g liver dry weight (mg/g dw) (median
      9.4 mg/g dw). Correlation between LIC by biopsy and by MRI with Gandon's
      procedure was good (R = 0.80) in patients with LIC falling within the range
      reported by Gandon. By contrast, a weak correlation was demonstrated (R = 0.52)
      in patients with high LIC (above 11.2 mg/g dw). With our sequences, the
      correlation was good both in the entire group of patients (R = 0.83) and in
      patients with LIC above 11.2 mg/g dw (R = 0.85). CONCLUSION: Our results suggest
      that the addition of a specific shorter-gradient echo sequence to a very simple,
      fast technique produces an accurate estimation of LIC in post-transfusional iron
      overload.

PMID- 16608502
TI  - Hydrops lysosomalis generalisatus--an underestimated side effect of hydroxyethyl
      starch therapy?
AB  - Hydroxyethyl starch (HES) is usually considered to be associated with limited
      side effects. Generalized foamy cell macrophage syndrome after HES therapy has
      rarely been reported since Schaefer first described it as 'hydrops lysosomalis
      generalisatus' in 1982. We present a 19-yr-old male who received large amounts of
      HES. A bone marrow and a liver biopsy were performed because of persistent
      thrombocytopenia and liver dysfunction. We found severe infiltration of foamy
      cell degenerated macrophages in both organ systems, indicating that sequelae of
      HES therapy have to be included in the differential diagnosis of bone marrow and
      liver dysfunction.

PMID- 16608503
TI  - Procoagulant factors and the risk of myocardial infarction in young women.
AB  - OBJECTIVES: We investigated whether elevated levels of factor VIII, IX and XI is
      associated with myocardial infarction (MI) in young women. In addition, we
      studied ABO blood group, von Willebrand factor (VWF) and C-reactive protein
      (CRP). METHODS AND RESULTS: We compared 200 women with MI before age 49 years
      with 626 controls from a population-based case-control study. Mean levels of
      factor VIII activity (VIII), von Willebrand factor antigen (VWF), factor IX
      activity (IX) were higher in patients (133, 134 and 132 IU/dL) than in controls
      (111, 107 and 120 IU/dL, respectively). Mean levels of factor XI (XI) were equal
      in patients (114 IU/dL) and controls (113 IU/dL). The odds ratio (OR) for MI for
      blood group non-O vs. O was 1.6 [95% confidence interval (CI) 1.1-2.3]. The OR
      adjusted for age, index year and area of residence for the highest quartile >150
      IU/dL of factor VIII was 2.7 (95% CI 1.6-4.6), of VWF 4.7 (95% CI 2.3-9.7), of
      factor IX 2.6 (95% CI 1.3-5.4) and of factor XI 0.9 (95% CI 0.5-1.4), all
      compared with the lowest quartile <100 IU/dL. CONCLUSIONS: Non-O blood group,
      high VWF, factor VIII and factor IX levels are associated with an increased risk
      of MI in young women, while high factor XI levels are not.

PMID- 16608505
TI  - Absence of mutations of the EPO-receptor gene in Greek patients with familial
      polycythemia.

PMID- 16608504
TI  - Medium-term results of percutaneous vertebroplasty in multiple myeloma.
AB  - Vertebral compression fractures (VCFs) are common in multiple myeloma (MM).
      Percutaneous vertebroplasty (PVP) is used to stabilize vertebral collapse and
      treat the pain. Few studies have been carried out on PVP in MM and follow-up has
      tended to be short. We have prospectively evaluated the safety and efficacy of
      PVP in the VCFs resulting from MM or plasmacytomas. Nineteen PVP were performed
      in 12 consecutive patients. We monitored their pain and functional status using
      visual analog (VAS) and Eastern Cooperative Oncology Group (ECOG) scale,
      respectively. For a subjective assessment, every patient was asked about his/her
      degree of satisfaction. The mean age of the participants was 66 yr. Significant
      improvement occurred 1 d after PVP according to the VAS score (7.5 pre-PVP to
      3.7, P < 0.0001) and ECOG assessment (3.1 to 2.5, P = 0.002). This significant
      improvement was maintained after 3.2 yr of follow-up. Sixty-three percent of
      patients were highly satisfied with the result of the PVP and 37% were satisfied.
      The peri-operative mortality was 0%. Leakage of the cement outside of the
      vertebral body was noted in 16 of 19 injected vertebrae (84%) but none of the
      patients developed any clinical or neurological symptoms. At the last follow-up,
      no further collapse in the treated or neighboring vertebrae was noted. VCFs
      caused by MM or plasmacytomas can be effectively treated by vertebroplasty. PVP
      is associated with early clinical improvement of pain and function and can be
      maintained after a long follow-up without major procedure-related complications.

PMID- 16608506
TI  - The results of imatinib therapy for patients with primary eosinophilic disorders.

PMID- 16608508
TI  - Life-threatening intoxication with methylene bis(thiocyanate): clinical picture
      and pitfalls. A case report.
AB  - BACKGROUND: Methylene bis(thiocyanate) (MBT) is a microbiocidal agent mainly used
      in industrial water cooling systems and paper mills as an inhibitor of algae,
      fungi, and bacteria. CASE PRESENTATION: We describe the first case of severe
      intoxication following inhalation of powder in an industrial worker. Profound
      cyanosis and respiratory failure caused by severe methemoglobinemia developed
      within several minutes. Despite immediate admission to the intensive care unit,
      where mechanical ventilation and hemodialysis for toxin elimination were
      initiated, multi-organ failure involving liver, kidneys, and lungs developed.
      While liver failure was leading, the patient was successfully treated with the
      MARS (molecular adsorbent recirculating system) procedure. CONCLUSION:
      Intoxication with MBT is a potentially life-threatening intoxication causing
      severe methemoglobinemia and multi-organ failure. Extracorporeal liver albumin
      dialysis (MARS) appears to be an effective treatment to allow recovery of hepatic
      function.

PMID- 16608507
TI  - Maternal health study: a prospective cohort study of nulliparous women recruited
      in early pregnancy.
AB  - BACKGROUND: In the first year after childbirth, 94% of women experience one or
      more major health problems (urinary incontinence, faecal incontinence, perineal
      pain, back pain). Difficulties in intimate partner relationships and changes
      affecting sexual health are also common. The aim of this study is to investigate
      changes in women's health from early pregnancy until four years after the birth
      of a first child. METHODS/DESIGN: The Maternal Health Study is a longitudinal
      study designed to fill in some of the gaps in current research evidence regarding
      women's physical and psychological health and recovery after childbirth. A
      prospective pregnancy cohort of >1500 nulliparous women has been recruited in
      early pregnancy at six metropolitan public hospitals in Melbourne, Australia
      between April 2003 and December 2005. In the first phase of the study
      participants are being followed up at 30-32 weeks gestation in pregnancy, and at
      three, six, nine, 12 and 18 months postpartum using a combination of self
      administered questionnaires and telephone interviews. Women consenting to
      extended follow-up (phase 2) will be followed up six and 12 months after any
      subsequent births and when their first child is four years old. Study instruments
      incorporate assessment of the frequency and severity of urinary and bowel
      symptoms, sexual health issues, perineal and abdominal pain, depression and
      intimate partner violence. Pregnancy and birth outcome data will be obtained by
      review of hospital case notes. DISCUSSION: Features of the study which
      distinguish it from prior research include: the capacity to identify incident
      cases of morbidity and clustering of health problems; a large enough sample to
      detect clinically important differences in maternal health outcomes associated
      with the method of birth; careful exposure measurement involving manual
      abstraction of data from medical records in order to explore mediating factors
      and possible causal pathways; and use of a variety of strategies to improve
      ascertainment of health outcomes.

PMID- 16608509
TI  - Successful treatment of Candida parapsilosis mural endocarditis with combined
      caspofungin and voriconazole.
AB  - BACKGROUND: Fungal mural endocarditis is a rare entity in which the antemortem
      diagnosis is seldom made. Seven cases of mural endocarditis caused by Candida
      spp. have been collected from literature and six of these patients died after
      treatment with amphotericin B. CASE PRESENTATION: We report a case of mural
      endocarditis diagnosed by transesophageal echocardiogram and positive blood
      cultures to Candida parapsilosis. Because blood cultures continued to yield C.
      parapsilosis despite caspofungin monotherapy, treatment with voriconazole was
      added. CONCLUSION: This is the first description of successful treatment of C.
      parapsilosis mural endocarditis with caspofungin and voriconazole.

PMID- 16608510
TI  - The implementation of quality management systems in hospitals: a comparison
      between three countries.
AB  - BACKGROUND: Is the implementation of Quality Management (QM) in health care
      proceeding satisfactorily and can national health care policies influence the
      implementation process? Policymakers and researchers in a country need to know
      the answer to this question. Cross country comparisons can reveal whether
      sufficient progress is being made and how this can be stimulated. The objective
      of the study was to investigate agreement and disparities in the implementation
      of QMS between The Netherlands, Hungary and Finland with respect to the
      evaluation model used and the national policy strategy of the three countries.
      METHODS: The study has a cross sectional design, based on measurements in 2000.
      Empirical data about QM-activities in hospitals were gathered by a self
      administered questionnaire. The questionnaires were answered by the directors of
      the hospitals or the quality coordinators. The analyses are based on data from
      101 hospitals in the Netherlands, 116 hospitals in Hungary and 59 hospitals in
      Finland. Outcome measures are the developmental stage of the Quality Management
      System (QMS), the development within five focal areas, and distinct QM-activities
      which were listed in the questionnaire. RESULTS: A mean of 22 QM-activities per
      hospital was found in the Netherlands and Finland versus 20 QM-activities in
      Hungarian hospitals. Only a small number of hospitals has already implemented a
      QMS (4% in The Netherlands,0% in Hungary and 3% in Finland). More hospitals in
      the Netherlands are concentrating on quality documents, whereas Finnish hospitals
      are concentrating on training in QM and guidelines. Cyclic quality improvement
      activities have been developed in the three countries, but in most hospitals the
      results were not used for improvements. All three countries pay hardly any
      attention to patient participation. CONCLUSION: The study demonstrates that the
      implementation of QM-activities can be measured at national level and that
      differences between countries can be assessed. The hypothesis that governmental
      legislation or financial reimbursement can stimulate the implementation of QM
      activities, more than voluntary recommendations, could not be confirmed. However,
      the results show that specific obligations can stimulate the implementation of QM
      activities more than general, framework legislation.

PMID- 16608511
TI  - Public perceptions of drinking water: a postal survey of residents with private
      water supplies.
AB  - BACKGROUND: In Canada, the legal responsibility for the condition of private
      water supplies, including private wells and cisterns, rests with their owners.
      However, there are reports that Canadians test these water supplies
      intermittently and that treatment of such water is uncommon. An estimated 45% of
      all waterborne outbreaks in Canada involve non-municipal systems. An
      understanding of the perceptions and needs of Canadians served by private water
      supplies is essential, as it would enable public health professionals to better
      target public education and drinking water policy. The purpose of this study was
      to investigate the public perceptions of private water supplies in the City of
      Hamilton, Ontario (Canada), with the intent of informing public education and
      outreach strategies within the population. METHODS: A cross-sectional postal
      survey of 246 residences with private water supplies was conducted in May 2004.
      Questions pertained to the perceptions of water quality and alternative water
      sources, water testing behaviours and the self-identified need for further
      information. RESULTS: Private wells, cisterns or both, were the source of
      household water for 71%, 16% and 13% of respondents, respectively. Although
      respondents rated their water quality highly, 80% also had concerns with its
      safety. The most common concerns pertained to bacterial and chemical
      contamination of their water supply and its potential negative effect on health.
      Approximately 56% and 61% of respondents used in-home treatment devices and
      bottled water within their homes, respectively, mainly due to perceived
      improvements in the safety and aesthetic qualities compared to regular tap water.
      Testing of private water supplies was performed infrequently: 8% of respondents
      tested at a frequency that meets current provincial guidelines. Two-thirds of
      respondents wanted more information on various topics related to private water
      supplies. Flyers and newspapers were the two media reported most likely to be
      used. CONCLUSION: Although respondents rated their water quality highly, the
      majority had concerns regarding the water from their private supply, and the use
      of bottled water and water treatment devices was extensive. The results of this
      study suggest important lines of inquiry and provide support and input for public
      education programs, particularly those related to private water testing, in this
      population.

PMID- 16608512
TI  - Evaluation of high-dose daptomycin for therapy of experimental Staphylococcus
      aureus foreign body infection.
AB  - BACKGROUND: Daptomycin is a novel cyclic lipopeptide whose bactericidal activity
      is not affected by current antibiotic resistance mechanisms displayed by S.
      aureus clinical isolates. This study reports the therapeutic activity of high
      dose daptomycin compared to standard regimens of oxacillin and vancomycin in a
      difficult-to-treat, rat tissue cage model of experimental therapy of chronic S.
      aureus foreign body infection. METHODS: The methicillin-susceptible S. aureus
      (MSSA) strain I20 is a clinical isolate from catheter-related sepsis. MICs, MBCs,
      and time-kill curves of each antibiotic were evaluated as recommended by NCCLS,
      including supplementation with physiological levels (50 mg/L) of Ca2+ for
      daptomycin. Two weeks after local infection of subcutaneously implanted tissue
      cages with MSSA I20, each animal received (i.p.) twice-daily doses of daptomycin,
      oxacillin, or vancomycin for 7 days, or was left untreated. The reductions of CFU
      counts in each treatment group were analysed by ANOVA and Newman-Keuls multiple
      comparisons procedures. RESULTS: The MICs and MBCs of daptomycin, oxacillin, or
      vancomycin for MSSA strain I20 were 0.5 and 1, 0.5 and 1, or 1 and 2 mg/L,
      respectively. In vitro elimination of strain I20 was more rapid with 8 mg/L of
      daptomycin compared to oxacillin or vancomycin. Twice-daily administered
      daptomycin (30 mg/kg), oxacillin (200 mg/kg), or vancomycin (50 mg/kg vancomycin)
      yielded bactericidal antibiotic levels in infected cage fluids throughout
      therapy. Before therapy, mean (+/- SEM) viable counts of strain I20 were 6.68 +/-
      0.10 log10 CFU/mL of cage fluid (n = 74). After 7 days of therapy, the mean (+/-
      SEM) reduction in viable counts of MSSA I20 was 2.62 (+/- 0.30) log10 CFU/mL in
      cages (n = 18) of daptomycin-treated rats, exceeding by > 2-fold (P < 0.01) the
      viable count reductions of 0.92 (+/- 0.23; n = 19) and 0.96 (+/- 0.24; n = 18)
      log10 CFU/mL in cages of oxacillin-treated and vancomycin-treated rats,
      respectively. Viable counts in cage fluids of untreated animals increased by 0.48
      (+/- 0.24; n = 19) log10 CFU/mL. CONCLUSION: The improved efficacy of the twice
      daily regimen of daptomycin (30 mg/kg) compared to oxacillin (200 mg/kg) or
      vancomycin (50 mg/kg) may result from optimisation of its pharmacokinetic and
      bactericidal properties in infected cage fluids.

PMID- 16608513
TI  - Prevention of catheter lumen occlusion with rT-PA versus heparin (Pre-CLOT):
      study protocol of a randomized trial [ISRCTN35253449].
AB  - BACKGROUND: Many patients with end-stage renal disease use a central venous
      catheter for hemodialysis access. A large majority of these catheters malfunction
      within one year of insertion, with up to two-thirds due to thrombosis. The
      optimal solution for locking the catheter between hemodialysis sessions, to
      decrease the risk of thrombosis and catheter malfunction, is unknown. The
      Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin (PreCLOT) study
      will determine if use of weekly rt-PA, compared to regular heparin, as a catheter
      locking solution, will decrease the risk of catheter malfunction. METHODS/DESIGN:
      The study population will consist of patients requiring chronic hemodialysis
      thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central
      venous catheter. Patients randomized to the treatment arm will receive rt-PA 1 mg
      per lumen once per week, with heparin 5,000 units per ml as a catheter locking
      solution for the remaining two sessions. Patients randomized to the control arm
      will receive heparin 5,000 units per ml as a catheter locking solution after each
      dialysis session. The study treatment period will be six months, with 340
      patients to be recruited from 14 sites across Canada. The primary outcome will be
      catheter malfunction, based on mean blood flow parameters while on hemodialysis,
      with a secondary outcome of catheter-related bacteremia. A cost-effectiveness
      analysis will be undertaken to assess the cost of maintaining a catheter using rt
      PA as a locking solution, compared to the use of heparin. DISCUSSION: Results
      from this study will determine if use of weekly rt-PA, compared to heparin, will
      decrease catheter malfunction, as well as assess the cost-effectiveness of these
      locking solutions.

PMID- 16608514
TI  - Soy protein supplementation does not cause lymphocytopenia in postmenopausal
      women.
AB  - BACKGROUND: The health benefits of soy isoflavones have been widely investigated;
      however, there are some concerns as to whether soy isoflavones, similar to
      ipriflavone, a synthetic isoflavone, cause lymphocytopenia in postmenopausal
      women. Hence, the purpose of this study was to investigate the extent to which 12
      month supplementation of 25 g soy protein containing 60 mg isoflavones alters
      lymphocyte counts or other hematological parameters in postmenopausal women who
      were not on hormone replacement therapy. METHODS: Eighty-seven postmenopausal
      women were randomly assigned to receive either soy protein or an equivalent
      amount of control protein devoid of isoflavones. Fasting venous blood was
      collected at baseline and at the end of twelve month study period for complete
      blood count analyses. RESULTS: Between the two treatment groups, the percent
      changes in hematological parameters, including lymphocytes, were not different.
      While women consuming the soy supplement had an increase in mean corpuscular
      hemoglobin concentration (MCHC) and red cell distribution width index (RDW; a
      marker of reticulocytes), women consuming the control diet had higher percentage
      of only MCHC. CONCLUSION: Overall, the results of the present study indicate that
      consumption of 25 g soy protein containing 60 mg isoflavones daily for one year
      does not cause lymphocytopenia.

PMID- 16608515
TI  - Biologically relevant effects of mRNA amplification on gene expression profiles.
AB  - BACKGROUND: Gene expression microarray technology permits the analysis of global
      gene expression profiles. The amount of sample needed limits the use of small
      excision biopsies and/or needle biopsies from human or animal tissues. Linear
      amplification techniques have been developed to increase the amount of sample
      derived cDNA. These amplified samples can be hybridised on microarrays. However,
      little information is available whether microarrays based on amplified and
      unamplified material yield comparable results. In the present study we compared
      microarray data obtained from amplified mRNA derived from biopsies of rat cardiac
      left ventricle and non-amplified mRNA derived from the same organ. Biopsies were
      linearly amplified to acquire enough material for a microarray experiment. Both
      amplified and unamplified samples were hybridized to the Rat Expression Set 230
      Array of Affymetrix. RESULTS: Analysis of the microarray data showed that
      unamplified material of two different left ventricles had 99.6% identical gene
      expression. Gene expression patterns of two biopsies obtained from the same
      parental organ were 96.3% identical. Similarly, gene expression pattern of two
      biopsies from dissimilar organs were 92.8% identical to each other.Twenty-one
      percent of reporters called present in parental left ventricular tissue
      disappeared after amplification in the biopsies. Those reporters were
      predominantly seen in the low intensity range. Sequence analysis showed that
      reporters that disappeared after amplification had a GC-content of 53.7+/-4.0%,
      while reporters called present in biopsy- and whole LV-samples had an average GC
      content of 47.8+/-5.5% (P <0.001). Those reporters were also predicted to form
      significantly more (0.76+/-0.07 versus 0.38+/-0.1) and longer (9.4+/-0.3 versus
      8.4+/-0.4) hairpins as compared to representative control reporters present
      before and after amplification. CONCLUSION: This study establishes that the gene
      expression profile obtained after amplification of mRNA of left ventricular
      biopsies is representative for the whole left ventricle of the rat heart.
      However, specific gene transcripts present in parental tissues were undetectable
      in the minute left ventricular biopsies. Transcripts that were lost due to the
      amplification process were not randomly distributed, but had higher GC-content
      and hairpins in the sequence and were mainly found in the lower intensity range
      which includes many transcription factors from specific signalling pathways.

PMID- 16608516
TI  - Whitefly (Bemisia tabaci) genome project: analysis of sequenced clones from egg,
      instar, and adult (viruliferous and non-viruliferous) cDNA libraries.
AB  - BACKGROUND: The past three decades have witnessed a dramatic increase in interest
      in the whitefly Bemisia tabaci, owing to its nature as a taxonomically cryptic
      species, the damage it causes to a large number of herbaceous plants because of
      its specialized feeding in the phloem, and to its ability to serve as a vector of
      plant viruses. Among the most important plant viruses to be transmitted by B.
      tabaci are those in the genus Begomovirus (family, Geminiviridae). Surprisingly,
      little is known about the genome of this whitefly. The haploid genome size for
      male B. tabaci has been estimated to be approximately one billion bp by flow
      cytometry analysis, about five times the size of the fruitfly Drosophila
      melanogaster. The genes involved in whitefly development, in host range
      plasticity, and in begomovirus vector specificity and competency, are unknown.
      RESULTS: To address this general shortage of genomic sequence information, we
      have constructed three cDNA libraries from non-viruliferous whiteflies (eggs,
      immature instars, and adults) and two from adult insects that fed on tomato
      plants infected by two geminiviruses: Tomato yellow leaf curl virus (TYLCV) and
      Tomato mottle virus (ToMoV). In total, the sequence of 18,976 clones was
      determined. After quality control, and removal of 5,542 clones of mitochondrial
      origin 9,110 sequences remained which included 3,843 singletons and 1,017
      contigs. Comparisons with public databases indicated that the libraries contained
      genes involved in cellular and developmental processes. In addition,
      approximately 1,000 bases aligned with the genome of the B. tabaci endosymbiotic
      bacterium Candidatus Portiera aleyrodidarum, originating primarily from the egg
      and instar libraries. Apart from the mitochondrial sequences, the longest and
      most abundant sequence encodes vitellogenin, which originated from whitefly adult
      libraries, indicating that much of the gene expression in this insect is directed
      toward the production of eggs. CONCLUSION: This is the first functional genomics
      project involving a hemipteran (Homopteran) insect from the subtropics/tropics.
      The B. tabaci sequence database now provides an important tool to initiate
      identification of whitefly genes involved in development, behaviour, and B.
      tabaci-mediated begomovirus transmission.

PMID- 16608517
TI  - Overexpression of ribosomal protein L15 is associated with cell proliferation in
      gastric cancer.
AB  - BACKGROUND: Ribosomal proteins are the components of ribosome, which also exhibit
      various secondary functions in DNA repair, apoptosis, drug resistance and
      proliferation. In our previous study of microarray, ribosomal protein L15 (RPL15)
      was identified as an upregulated gene in gastric cancer. METHODS: We investigated
      the expression of ribosomal protein L15 in gastric cancer and the effect of RPL15
      on proliferation of gastric cancer. RESULTS: It was found that the expression of
      RPL15 was markedly up-regulated in gastric cancer tissues. RPL15 was also highly
      expressed in gastric cancer cell lines AGS, MKN45, MKN28, SGC7901 and KATOIII.
      Inhibition of RPL15 expression by siRNA vector transfection suppressed the growth
      of SGC7901 cells significantly, which was independent of the expression of Cyclin
      D1 and B1. Down-regulation of RPL15 expression inhibited SGC7901 cell growth in
      soft agar and its tumorigenicity in nude mice. CONCLUSION: RPL15 promotes cell
      proliferation and may be a potential target for anticancer therapy of gastric
      cancer.

PMID- 16608518
TI  - Modes of transmission and genetic diversity of foamy viruses in a Macaca tonkeana
      colony.
AB  - BACKGROUND: Foamy viruses are exogenous complex retroviruses that are highly
      endemic in several animal species, including monkeys and apes, where they cause
      persistent infection. Simian foamy viral (SFV) infection has been reported in few
      persons occupationally exposed to non-human primates (NHP) in zoos, primate
      centers and laboratories, and recently in few hunters from central Africa. Most
      of the epidemiological works performed among NHP populations concern cross
      sectional studies without long-term follow-up. Therefore, the exact timing and
      the modes of transmission of SFVs remain not well known, although sexual and oral
      transmissions have been suspected. We have conducted a longitudinal study in a
      free-breeding colony of Macaca tonkeana in order (1) to determine the prevalence
      of the infection by foamy viruses, (2) to characterize molecularly the viruses
      infecting such animals, (3) to study their genetic variability overtime by long
      term follow-up of several DNA samples in a series of specific animals, and (4) to
      get new insights concerning the timing and the modes of SFVs primary infection in
      these monkeys by combining serology and molecular means, as well as studies of
      familial structures and long-term behavioral observations. RESULTS/CONCLUSION: We
      first demonstrated that this colony was highly endemic for SFVs, with a clear
      increase of seroprevalence with age. Only 4.7% of immatures, and 43,7% of sub
      adults were found seropositive, while 89.5% of adults exhibited antibodies
      directed against SFV. We further showed that 6 different strains of foamy viruses
      (exhibiting a very low intra-strain and overtime genetic variability in the
      integrase gene) are circulating within this group. This suggests a possible
      infection by different strains within an animal. Lastly, we provide strong
      evidence that foamy viruses are mostly acquired through severe bites, mainly in
      sub-adults or young adults. Most cases of seroconversion occur after 7 years of
      age; from this age individuals competed for access to sexual partners, thus
      increasing the likelihood of being wounded. Furthermore, all the serological and
      molecular data, obtained in this free-breeding colony, argue against a
      significant transmission of SFVs from mother or father to infants as well as
      between siblings.

PMID- 16608519
TI  - A descriptive study of youth risk behavior in urban and rural secondary school
      students in El Salvador.
AB  - BACKGROUND: Adolescence is an important stage of life for establishing healthy
      behaviors, attitudes, and lifestyles that contribute to current and future
      health. Health risk behavior is one indicator of health of young people that may
      serve both as a measure of health over time as well as a target for health
      policies and programs. This study examined the prevalence and distribution of
      youth health risk behaviors from five risk behavior domains-aggression,
      victimization, depression and suicidal ideation, substance use, and sexual
      behaviors-among public secondary school students in central El Salvador. METHODS:
      We employed a multi-stage sampling design in which school districts, schools, and
      classrooms were randomly selected. Data were collected using a self-administered
      questionnaire based on the United States Center for Disease Control and
      Prevention's Youth Risk Behavior Survey. Sixteen schools and 982 students aged 12
      20 years participated in the study. RESULTS: Health risk behaviors with highest
      prevalence rates included: engagement in physical fight (32.1%);
      threatened/injured with a weapon (19.9%); feelings of sadness/hopelessness
      (32.2%); current cigarette use (13.6%); and no condom use at last sexual
      intercourse (69.1%). Urban and male students reported statistically significant
      higher prevalence of most youth risk behaviors; female students reported
      statistically significant higher prevalence of feelings of sadness/hopelessness
      (35.6%), suicidal ideation (17.9%) and, among the sexually experienced, forced
      sexual intercourse (20.6%). CONCLUSION: A high percentage of Salvadoran
      adolescents in this sample engaged in health risk behaviors, warranting enhanced
      adolescent health promotion strategies. Future health promotion efforts should
      target: the young age of sexual intercourse as well as low condom use among
      students, the higher prevalence of risk behaviors among urban students, and the
      important gender differences in risk behaviors, including the higher prevalence
      of reported feelings of sadness, suicidal ideation and forced sexual intercourse
      among females and higher sexual intercourse and substance use among males.
      Relevance of findings within the Salvadoran and the cross-national context and
      implications for health promotion efforts are discussed.

PMID- 16608520
TI  - Identification of acid reflux cough using serial assays of exhaled breath
      condensate pH.
AB  - BACKGROUND: Chronic cough is a common problem, frequently caused or exacerbated
      by acid reflux. Diagnosis of acid reflux cough is haphazard currently, often
      relying on long therapeutic trials of expensive medications. We tested the
      hypothesis that the most relevant mechanistic component of acid reflux in chronic
      cough is when it rises to the level of the airway where acid can potentially be
      aspirated. We further wished to determine if multi-sample exhaled breath
      condensate (EBC) pH profiles can identify chronic cough patients likely to
      respond to proton pump inhibitor therapy. METHODS: 59 subjects were recruited for
      this study. Initially we examined EBC pH (gas-standardized with Argon) in the
      setting of 15 experimental pharyngeal acid challenges to determine duration of
      EBC acidification. Subsequently, we enrolled 22 healthy subjects to determine a
      normal multi-sample exhaled breath condensate pH profile over 1-3 days. We
      additionally obtained multi-sample EBC pH profiles in 22 patients with chronic
      cough. These samples were timed to occur after coughing episodes. Exhaled breath
      condensate pH was measured after gas standardization. RESULTS: We found that
      exhaled breath condensate pH is substantially reduced for approximately 15
      minutes after pharyngeal acid load. Healthy subjects rarely have any low EBC pH
      values (defined as < 7.4 based on a normative reference range from 404 healthy
      subjects). Patients with chronic cough who subsequently responded well to proton
      pump inhibition (n = 8) invariably had one or more cough episodes associated with
      EBC acidification. No patient who had normal EBC pH with each of their cough
      episodes reported a clinically relevant response to proton-pump inhibition.
      CONCLUSION: Patients whose cough responds to proton pump inhibition have
      transient exhaled breath condensate acidification with coughing episodes,
      supporting the role of airway acidification in reflux-triggered cough. Multi
      sample EBC pH profiles, involving samples collected immediately subsequent to a
      coughing episode, may be useful appropriately to direct therapy to those patients
      with cough who have relevant acid reflux.

PMID- 16608521
TI  - Estrogen-induced DNA synthesis in vascular endothelial cells is mediated by ROS
      signaling.
AB  - BACKGROUND: Since estrogen is known to increase vascular endothelial cell growth,
      elevated estrogen exposure from hormone replacement therapy or oral
      contraceptives has the potential to contribute in the development of abnormal
      proliferative vascular lesions and subsequent thickening of the vasculature. How
      estrogen may support or promote vascular lesions is not clear. We have examined
      in this study whether estrogen exposure to vascular endothelial cells increase
      the formation of reactive oxygen species (ROS), and estrogen-induced ROS is
      involved in the growth of endothelial cells. METHODS: The effect of estrogen on
      the production of intracellular oxidants and the role of estrogen-induced ROS on
      cell growth was studied in human umbilical vein endothelial cells. ROS were
      measured by monitoring the oxidation of 2'7'-dichlorofluorescin by
      spectrofluorometry. Endothelial cell growth was measured by a colorimetric
      immunoassay based on BrdU incorporation into DNA. RESULTS: Physiological
      concentrations of estrogen (367 fmol and 3.67 pmol) triggered a rapid 2-fold
      increase in intracellular oxidants in endothelial cells. E2-induced ROS formation
      was inhibited to basal levels by cotreatment with the mitochondrial inhibitor
      rotenone (2 microM) and xanthine oxidase inhibitor allopurinol (50 microM).
      Inhibitors of NAD(P)H oxidase, apocynin and DPI, did not block E2-induced ROS
      formation. Furthermore, the NOS inhibitor, L-NAME, did not prevent the increase
      in E2-induced ROS. These findings indicate both mitochondria and xanthine oxidase
      are the source of ROS in estrogen treated vascular endothelial cells. E2 treated
      cells showed a 2-fold induction of BrdU incorporation at 18 h which was not
      observed in cells exposed to vehicle alone. Cotreatment with ebselen (20 microM)
      and NAC (1 mM) inhibited E2-induced BrdU incorporation without affecting the
      basal levels of DNA synthesis. The observed inhibitory effect of NAC and ebselen
      on E2-induced DNA synthesis was also shown to be dose dependent. CONCLUSION: We
      have shown that estrogen exposure stimulates the rapid production of
      intracellular ROS and they are involved in growth signaling of endothelial cells.
      It appears that the early estrogen signaling does not require estrogen receptor
      genomic signaling because we can inhibit estrogen-induced DNA synthesis by
      antioxidants. Findings of this study may further expand research defining the
      underlying mechanism of how estrogen may promote vascular lesions. It also
      provides important information for the design of new antioxidant-based drugs or
      new antioxidant gene therapy to protect the cardiovascular health of individuals
      sensitive to estrogen.

PMID- 16608522
TI  - A phylogenomic gene cluster resource: the Phylogenetically Inferred Groups
      (PhIGs) database.
AB  - BACKGROUND: We present here the PhIGs database, a phylogenomic resource for
      sequenced genomes. Although many methods exist for clustering gene families, very
      few attempt to create truly orthologous clusters sharing descent from a single
      ancestral gene across a range of evolutionary depths. Although these non
      phylogenetic gene family clusters have been used broadly for gene annotation,
      errors are known to be introduced by the artifactual association of slowly
      evolving paralogs and lack of annotation for those more rapidly evolving. A full
      phylogenetic framework is necessary for accurate inference of function and for
      many studies that address pattern and mechanism of the evolution of the genome.
      The automated generation of evolutionary gene clusters, creation of gene trees,
      determination of orthology and paralogy relationships, and the correlation of
      this information with gene annotations, expression information, and genomic
      context is an important resource to the scientific community. DISCUSSION: The
      PhIGs database currently contains 23 completely sequenced genomes of fungi and
      metazoans, containing 409,653 genes that have been grouped into 42,645 gene
      clusters. Each gene cluster is built such that the gene sequence distances are
      consistent with the known organismal relationships and in so doing, maximizing
      the likelihood for the clusters to represent truly orthologous genes. The PhIGs
      website contains tools that allow the study of genes within their phylogenetic
      framework through keyword searches on annotations, such as GO and InterPro
      assignments, and sequence similarity searches by BLAST and HMM. In addition to
      displaying the evolutionary relationships of the genes in each cluster, the
      website also allows users to view the relative physical positions of homologous
      genes in specified sets of genomes. SUMMARY: Accurate analyses of genes and
      genomes can only be done within their full phylogenetic context. The PhIGs
      database and corresponding website http://phigs.org address this problem for the
      scientific community. Our goal is to expand the content as more genomes are
      sequenced and use this framework to incorporate more analyses.

PMID- 16608523
TI  - Profiling alternatively spliced mRNA isoforms for prostate cancer classification.
AB  - BACKGROUND: Prostate cancer is one of the leading causes of cancer illness and
      death among men in the United States and world wide. There is an urgent need to
      discover good biomarkers for early clinical diagnosis and treatment. Previously,
      we developed an exon-junction microarray-based assay and profiled 1532 mRNA
      splice isoforms from 364 potential prostate cancer related genes in 38 prostate
      tissues. Here, we investigate the advantage of using splice isoforms, which
      couple transcriptional and splicing regulation, for cancer classification.
      RESULTS: As many as 464 splice isoforms from more than 200 genes are
      differentially regulated in tumors at a false discovery rate (FDR) of 0.05.
      Remarkably, about 30% of genes have isoforms that are called significant but do
      not exhibit differential expression at the overall mRNA level. A support vector
      machine (SVM) classifier trained on 128 signature isoforms can correctly predict
      92% of the cases, which outperforms the classifier using overall mRNA abundance
      by about 5%. It is also observed that the classification performance can be
      improved using multivariate variable selection methods, which take correlation
      among variables into account. CONCLUSION: These results demonstrate that
      profiling of splice isoforms is able to provide unique and important information
      which cannot be detected by conventional microarrays.

PMID- 16608524
TI  - Crossmodal attention effects on brain responses to different stimulus classes.
AB  - BACKGROUND: Attending to a point in space in one modality may facilitate
      processing to information from the same region in another modality. The
      involvement of sensory-specific cortical areas in intramodal and crossmodal
      selective spatial attention can be assessed with event-related brain potentials
      (ERPs). ERPs were recorded in two groups of young participants (each n = 11).
      Stimulus sequences comprised visual standard stimuli (p = 0.4, a white square),
      visual deviant stimuli (p = 0.05, a white square with small black rectangle) and
      visual novel stimuli (p = 0.05, different multicolored checkerboards) as well as
      auditory standard (p = 0.4, 800 Hz tone), deviant (p = 0.05, 900 Hz tone), and
      novel (p = 0.05, random combination of three sine-wave tones) stimuli, occurring
      in random order at locations 30 degrees left and right of a fixation point. The
      "auditory group" of participants attended either to the left or to the right
      speaker in order to respond to the infrequent auditory deviants at that location
      by a speeded button press. Visual stimuli were irrelevant for this group. The
      "visual group" had the analogue task for the visual modality. For these
      participants auditory stimuli were irrelevant throughout the experiment. RESULTS:
      ERPs showed a typical enhancement of early sensory specific components by
      intramodal spatial attention (visual group: visual P1 and N1; auditory group:
      auditory Nd). Crossmodal spatial attention effects included a modulation of the
      Nd to auditory standards in the visual group and a modulation of the P1 to visual
      novels and N1 for visual standards for the auditory group. Similar to previous
      studies crossmodal spatial attention effects on visual standard and novel stimuli
      also included a frontocentral positivity in the 200-400 ms range that was not
      seen for intramodal spatial visual attention suggesting involvement of later
      supramodal areas. CONCLUSION: These findings are consistent with an action of
      crossmodal spatial attention on early, sensory specific processing stages.

PMID- 16608525
TI  - Patterns of sports sponsorship by gambling, alcohol and food companies: an
      Internet survey.
AB  - BACKGROUND: Sports sponsorship is a significant marketing tool. As such, it can
      promote products that pose risks to health (eg, high fat and high sugar foods) or
      it can promote health-supporting products (eg, sporting equipment and services).
      However, there is a lack of data on the proportion of sponsorship associated with
      "unhealthy" and "healthy" products and no methodology for systematically
      assessing it. This research aimed to explore this proportion with an Internet
      survey of sports sponsorship in the New Zealand setting. METHODS: A search
      methodology was developed to identify Internet-based evidence of sports
      sponsorship at the national level and at the regional and club level in one
      specific region (Wellington). The top eight sports for 5-17-year-olds were
      selected and products and services of sponsors were classified in terms of
      potential public health impact (using a conservative approach). RESULTS:
      Sponsorship of these popular sports was common at the national, regional and club
      levels (640 sponsors listed on 107 websites overall). Sports sponsorship
      associated with sponsors' products classified as "unhealthy" (eg, food high in
      fat and sugar, gambling and alcohol) were over twice as common as sponsorship
      associated with sponsors' products classified as "healthy" (32.7% (95% CI = 29.1,
      36.5) versus 15.5% (95% CI = 12.8, 18.6) respectively). "Gambling" was the most
      common specific type of sponsorship (18.8%) followed by alcohol (11.3%). There
      were significantly more "alcohol" sponsors for rugby, compared to all the other
      sports collectively (rate ratio (RR) = 2.47; 95% CI = 1.60, 3.79), and for top
      male sports compared to female (RR = 1.83; 95% CI = 1.05, 3.18). Also there was
      significantly more "unhealthy food" sponsorship for touch rugby and for "junior"
      teams/clubs compared to other sports collectively (RR = 6.54; 95% CI = 2.07,
      20.69; and RR = 14.72, 95% CI = 6.22, 34.8; respectively). A validation study
      gave an inter-rater reliability for number of sponsors of 95% (n = 87 sponsors),
      and an inter-rater reliability of classification and categorisation of 100%.
      CONCLUSION: This study found that the sponsorship of popular sports for young
      people is dominated by "unhealthy" sponsorship (ie, predominantly gambling,
      alcohol and unhealthy food) relative to "healthy" sponsorship. Governments may
      need to consider regulations that limit unhealthy sponsorship and/or adopt
      alternative funding mechanisms for supporting popular sports.

PMID- 16608526
TI  - A broadly applicable method to characterize large DNA viruses and adenoviruses
      based on the DNA polymerase gene.
AB  - BACKGROUND: Many viral pathogens are poorly characterized, are difficult to
      culture or reagents are lacking for confirmatory diagnoses. We have developed and
      tested a robust assay for detecting and characterizing large DNA viruses and
      adenoviruses. The assay is based on the use of degenerate PCR to target a gene
      common to these viruses, the DNA polymerase, and sequencing the products.
      RESULTS: We evaluated our method by applying it to fowl adenovirus isolates,
      catfish herpesvirus isolates, and largemouth bass ranavirus (iridovirus) from
      cell culture and lymphocystis disease virus (iridovirus) and avian poxvirus from
      tissue. All viruses with the exception of avian poxvirus produced the expected
      product. After optimization of extraction procedures, and after designing and
      applying an additional primer we were able to produce polymerase gene product
      from the avian poxvirus genome. The sequence data that we obtained demonstrated
      the simplicity and potential of the method for routine use in characterizing
      large DNA viruses. The adenovirus samples were demonstrated to represent 2 types
      of fowl adenovirus, fowl adenovirus 1 and an uncharacterized avian adenovirus
      most similar to fowl adenovirus 9. The herpesvirus isolate from blue catfish was
      shown to be similar to channel catfish virus (Ictalurid herpesvirus 1). The case
      isolate of largemouth bass ranavirus was shown to exactly match the type specimen
      and both were similar to tiger frog virus and frog virus 3. The lymphocystis
      disease virus isolate from largemouth bass was shown to be related but distinct
      from the two previously characterized lymphocystis disease virus isolates
      suggesting that it may represent a distinct lymphocystis disease virus species.
      CONCLUSION: The method developed is rapid and broadly applicable to cell culture
      isolates and infected tissues. Targeting a specific gene for in the large DNA
      viruses and adenoviruses provide a common reference for grouping the newly
      identified viruses according to relatedness to sequences of reference viruses and
      the submission of the sequence data to GenBank will build the database to make
      the BLAST analysis a valuable resource readily accessible by most diagnostic
      laboratories. We demonstrated the utility of this assay on viruses that infect
      fish and birds. These hosts are phylogenetically distant from mammals yet,
      sequence data suggests that the assay would work equally as well on mammalian
      counterparts of these groups of viruses. Furthermore, we demonstrated that
      obtaining genetic information on routine diagnostic samples has great potential
      for revealing new virus strains and suggesting the presence of new species.

PMID- 16608527
TI  - Spontaneous intracranial arterial dissection in the young: diagnosis by CT
      angiography.
AB  - BACKGROUND: Spontaneous carotid artery dissections have been rarely reported in
      children. Diagnosis has traditionally been confirmed by catheter arteriography.
      More recently diagnosis has been made by magnetic resonance imaging and magnetic
      resonance angiography; however the sensitivity of these techniques has yet to be
      determined. The authors are unaware of reports of carotid dissection confirmed by
      dynamic computed tomography (computerized tomographic arteriography) in the
      young. CASE PRESENTATION: We recently evaluated a fourteen year-old male
      following the development of transient neurologic symptoms. There was no
      antecedent illness or trauma. Dynamic computed tomography revealed an
      intracranial dissection involving the supraclinoid segment of the left internal
      carotid artery (confirmed by catheter arteriography). Studies for vasculitis, pro
      thrombotic states, and defects of collagen were negative. CONCLUSION: Spontaneous
      carotid artery dissection is a potential cause of transient neurological symptoms
      and ischemic stroke in the pediatric population. Dynamic computed tomography
      appears to be a reliable diagnostic tool which can lead to early diagnosis.

PMID- 16608529
TI  - The North West Adelaide Health Study: detailed methods and baseline segmentation
      of a cohort for selected chronic diseases.
AB  - The North West Adelaide Health Study is a population-based biomedical cohort
      study investigating the prevalence of a number of chronic conditions and health
      related risk factors along a continuum. This methodology may assist with evidence
      based decisions for health policy makers and planners, and inform health
      professionals who are involved in chronic disease prevention and management, by
      providing a better description of people at risk of developing or already
      diagnosed with selected chronic conditions for more accurate targeting groups for
      health gain and improved health outcomes. Longitudinal data will provide
      information on progression of chronic conditions and allow description of those
      who move forward and back along the continuum over time. Detailed methods are
      provided regarding the random recruitment and examination of a representative
      sample of participants (n = 4060), including the rationale for various processes
      and valuable lessons learnt. Self-reported and biomedical data were obtained on
      risk factors (smoking, alcohol consumption, physical activity, family history,
      body mass index, blood pressure, cholesterol) and chronic conditions (asthma,
      chronic obstructive pulmonary disease, diabetes) to classify participants
      according to their status along a continuum. Segmenting this population sample
      along a continuum showed that 71.5% had at least one risk factor for developing
      asthma, chronic obstructive pulmonary disease or diabetes. Almost one-fifth
      (18.8%) had been previously diagnosed with at least one of these chronic
      conditions, and an additional 3.9% had at least one of these conditions but had
      not been diagnosed. This paper provides a novel opportunity to examine how a
      cohort study was born. It presents detailed methodology behind the selection,
      recruitment and examination of a cohort and how participants with selected
      chronic conditions can be segmented along a continuum that may assist with health
      promotion and health services planning.

PMID- 16608528
TI  - Genetic polymorphisms and susceptibility to lung disease.
AB  - Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic
      basis in mice and may also have a genetic basis in humans. In the limited human
      cases of inhalation anthrax, studies suggest that not all individuals exposed to
      anthrax spores were infected, but rather, individuals with underlying lung
      disease, particularly asthma, sarcoidosis and tuberculosis, might be more
      susceptible. In this study, we determined if polymorphisms in genes important in
      innate immunity are associated with increased susceptibility to infectious and
      non-infectious lung diseases, particularly tuberculosis and sarcoidosis,
      respectively, and therefore might be a risk factor for inhalation anthrax.
      Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1),
      p67phox (NCF2), p40phox (NCF4), p22phox (CYBA), gp91phox (CYBB), DUOX1, DUOX2,
      TLR2, TLR9 and alpha 1-antitrypsin (AAT) in a cohort of 95 lung disease
      individuals and 95 control individuals did not show an association of these
      polymorphisms with increased susceptibility to lung disease.

PMID- 16608530
TI  - Chlamydia pneumoniae, heat shock proteins 60 and risk of secondary cardiovascular
      events in patients with coronary heart disease under special consideration of
      diabetes: a prospective study.
AB  - BACKGROUND: There have been suggestions of an association between Chlamydia
      pneumoniae, chlamydial heat shock protein (Ch-hsp) 60 and human heat shock
      protein (h-hsp) 60 infection sero-status and development of secondary
      cardiovascular events. Patients with diabetes might be at higher risk since they
      are prone to infections. The objective of this study was to investigate
      prospectively the role of Chlamydia pneumoniae (CP), chlamydial heat shock
      protein (Ch-hsp) 60 and a possible intermediate role of human heat shock protein
      (h-hsp) 60 sero-status in the development of secondary cardiovascular disease
      (CVD) events in patients with coronary heart disease (CHD) under special
      consideration of diabetes mellitus. METHODS: Patients aged 30-70 undergoing an in
      patient rehabilitation program after acute manifestation of coronary heart
      disease (International Classification of Disease, 9th Rev. pos. 410-414) between
      January 1999 and May 2000 in one of two participating rehabilitation clinics in
      Germany were included in this analysis. Chlamydia pneumoniae (CP), chlamydial
      heat shock protein (Ch-hsp) 60 and human heat shock protein (h-hsp) 60 status at
      baseline were measured by serum immunoglobulin G and A antibodies. Secondary CVD
      events (myocardial infarction, stroke, and cardiovascular death) were recorded
      during a mean follow-up period of 33.5 months (response = 87%). RESULTS: Among
      the 1052 subjects 37.4% and 39.3% were sero-positive to CP IgA and IgG
      respectively, 22.2% were sero-positive to Ch-hsp 60 IgG and 8.4% were positive to
      h-hsp 60 IgG at baseline. During follow-up, secondary CVD events occurred among
      71 (6.8%) participants. Occurrence of a secondary CVD event was more common among
      CP (IgA) and CP (IgG) sero-positive than among sero-negative patients (p-values
      0.04 and 0.1, respectively). The risk of secondary CVD events was increased among
      patients with both a positive CP sero-status and diabetes compared to infection
      negative, non-diabetic patients and in general, sero-positivity added a hazard to
      diabetes. The interaction term between infection sero-status and diabetes was not
      statistically significant. We were not able to show an intermediate role of human
      heat shock protein (h-hsp) 60 sero-status in the development of secondary CVD
      events in patients with CHD. CONCLUSION: Results from this cohort of 1052
      patients with pre-existing CHD cannot exclude a possible moderate increase in
      risk of secondary CVD events among patients with a positive infection sero
      status. However, our study showed no intermediate role of human heat shock
      protein (h-hsp) 60 sero-status in the development of secondary CVD events in
      patients with CHD. Larger studies or meta-analysis of multiple studies are needed
      to address the interaction between infection sero-status and diabetes with
      adequate power.

PMID- 16608532
TI  - A simulation study of three methods for detecting disease clusters.
AB  - BACKGROUND: Cluster detection is an important part of spatial epidemiology
      because it can help identifying environmental factors associated with disease and
      thus guide investigation of the aetiology of diseases. In this article we study
      three methods suitable for detecting local spatial clusters: (1) a spatial scan
      statistic (SaTScan), (2) generalized additive models (GAM) and (3) Bayesian
      disease mapping (BYM). We conducted a simulation study to compare the methods.
      Seven geographic clusters with different shapes were initially chosen as high
      risk areas. Different scenarios for the magnitude of the relative risk of these
      areas as compared to the normal risk areas were considered. For each scenario the
      performance of the methods were assessed in terms of the sensitivity,
      specificity, and percentage correctly classified for each cluster. RESULTS: The
      performance depends on the relative risk, but all methods are in general suitable
      for identifying clusters with a relative risk larger than 1.5. However, it is
      difficult to detect clusters with lower relative risks. The GAM approach had the
      highest sensitivity, but relatively low specificity leading to an overestimation
      of the cluster area. Both the BYM and the SaTScan methods work well. Clusters
      with irregular shapes are more difficult to detect than more circular clusters.
      CONCLUSION: Based on our simulations we conclude that the methods differ in their
      ability to detect spatial clusters. Different aspects should be considered for
      appropriate choice of method such as size and shape of the assumed spatial
      clusters and the relative importance of sensitivity and specificity. In general,
      the BYM method seems preferable for local cluster detection with relatively high
      relative risks whereas the SaTScan method appears preferable for lower relative
      risks. The GAM method needs to be tuned (using cross-validation) to get
      satisfactory results.

PMID- 16608531
TI  - Role of acetylcholine and polyspecific cation transporters in serotonin-induced
      bronchoconstriction in the mouse.
AB  - BACKGROUND: It has been proposed that serotonin (5-HT)-mediated constriction of
      the murine trachea is largely dependent on acetylcholine (ACh) released from the
      epithelium. We recently demonstrated that ACh can be released from non-neuronal
      cells by corticosteroid-sensitive polyspecific organic cation transporters
      (OCTs), which are also expressed by airway epithelial cells. Hence, the
      hypothesis emerged that 5-HT evokes bronchoconstriction by inducing release of
      ACh from epithelial cells via OCTs. METHODS: We tested this hypothesis by
      analysing bronchoconstriction in precision-cut murine lung slices using OCT and
      muscarinic ACh receptor knockout mouse strains. Epithelial ACh content was
      measured by HPLC, and the tissue distribution of OCT isoforms was determined by
      immunohistochemistry. RESULTS: Epithelial ACh content was significantly higher in
      OCT1/2 double-knockout mice (42 +/- 10 % of the content of the epithelium-denuded
      trachea, n = 9) than in wild-type mice (16.8 +/- 3.6 %, n = 11). In wild-type
      mice, 5-HT (1 microM) caused a bronchoconstriction that slightly exceeded that
      evoked by muscarine (1 microM) in intact bronchi but amounted to only 66% of the
      response to muscarine after epithelium removal. 5-HT-induced bronchoconstriction
      was undiminished in M2/M3 muscarinic ACh receptor double-knockout mice which were
      entirely unresponsive to muscarine. Corticosterone (1 microM) significantly
      reduced 5-HT-induced bronchoconstriction in wild-type and OCT1/2 double-knockout
      mice, but not in OCT3 knockout mice. This effect persisted after removal of the
      bronchial epithelium. Immunohistochemistry localized OCT3 to the bronchial smooth
      muscle. CONCLUSION: The doubling of airway epithelial ACh content in OCT1/2-/-
      mice is consistent with the concept that OCT1 and/or 2 mediate ACh release from
      the respiratory epithelium. This effect, however, does not contribute to 5-HT
      induced constriction of murine intrapulmonary bronchi. Instead, this activity
      involves 1) a non-cholinergic epithelium-dependent component, and 2) direct
      stimulation of bronchial smooth muscle cells, a response which is partly
      sensitive to acutely administered corticosterone acting on OCT3. These data
      provide new insights into the mechanisms involved in 5-HT-induced
      bronchoconstriction, including novel information about non-genomic, acute effects
      of corticosteroids on bronchoconstriction.

PMID- 16608533
TI  - Genomic alterations identified by array comparative genomic hybridization as
      prognostic markers in tamoxifen-treated estrogen receptor-positive breast cancer.
AB  - BACKGROUND: A considerable proportion of estrogen receptor (ER)-positive breast
      cancer recurs despite tamoxifen treatment, which is a serious problem commonly
      encountered in clinical practice. We tried to find novel prognostic markers in
      this subtype of breast cancer. METHODS: We performed array comparative genomic
      hybridization (CGH) with 1,440 human bacterial artificial chromosome (BAC) clones
      to assess copy number changes in 28 fresh-frozen ER-positive breast cancer
      tissues. All of the patients included had received at least 1 year of tamoxifen
      treatment. Nine patients had distant recurrence within 5 years (Recurrence group)
      of diagnosis and 19 patients were alive without disease at least 5 years after
      diagnosis (Non-recurrence group). RESULTS: Potential prognostic variables were
      comparable between the two groups. In an unsupervised clustering analysis,
      samples from each group were well separated. The most common regions of gain in
      all samples were 1q32.1, 17q23.3, 8q24.11, 17q12-q21.1, and 8p11.21, and the most
      common regions of loss were 6q14.1-q16.3, 11q21-q24.3, and 13q13.2-q14.3, as
      called by CGH-Explorer software. The average frequency of copy number changes was
      similar between the two groups. The most significant chromosomal alterations
      found more often in the Recurrence group using two different statistical methods
      were loss of 11p15.5-p15.4, 1p36.33, 11q13.1, and 11p11.2 (adjusted p values <
      0.001). In subgroup analysis according to lymph node status, loss of 11p15 and
      1p36 were found more often in Recurrence group with borderline significance
      within the lymph node positive patients (adjusted p = 0.052). CONCLUSION: Our
      array CGH analysis with BAC clones could detect various genomic alterations in ER
      positive breast cancers, and Recurrence group samples showed a significantly
      different pattern of DNA copy number changes than did Non-recurrence group
      samples.

PMID- 16608534
TI  - Monitoring the referral system through benchmarking in rural Niger: an evaluation
      of the functional relation between health centres and the district hospital.
AB  - BACKGROUND: The main objective of this study is to establish a benchmark for
      referral rates in rural Niger so as to allow interpretation of routine referral
      data to assess the performance of the referral system in Niger. METHODS: Strict
      and controlled application of existing clinical decision trees in a sample of
      rural health centres allowed the estimation of the corresponding need for and
      characteristics of curative referrals in rural Niger. Compliance of referral was
      monitored as well. Need was matched against actual referral in 11 rural
      districts. The referral patterns were registered so as to get an idea on the
      types of pathology referred. RESULTS: The referral rate benchmark was set at 2.5
      % of patients consulting at the health centre for curative reasons. Niger's rural
      districts have a referral rate of less than half this benchmark. Acceptability of
      referrals is low for the population and is adding to the deficient referral
      system in Niger. Mortality because of under-referral is highest among young
      children. CONCLUSION: Referral patterns show that the present programme approach
      to deliver health care leaves a large amount of unmet need for which only
      comprehensive first and second line health services can provide a proper answer.
      On the other hand, the benchmark suggests that well functioning health centres
      can take care of the vast majority of problems patients present with.

PMID- 16608536
TI  - Diagnosing epilepsy.
AB  - We know how important it is to diagnose epilepsy correctly, but how to do so is
      surprisingly little validated. An inadequate history and misinterpretation of the
      electroencephalogram (EEG) are the major reasons 4 to 26% of children and adults
      in European studies are misdiagnosed with epilepsy. Error rates are not available
      for most countries, or for more precise diagnoses of seizure types, epilepsy
      syndrome, and cause.

PMID- 16608535
TI  - Tumor-specific expression of alphavbeta3 integrin promotes spontaneous metastasis
      of breast cancer to bone.
AB  - INTRODUCTION: Studies in xenograft models and experimental models of metastasis
      have implicated several beta3 integrin-expressing cell populations, including
      endothelium, platelets and osteoclasts, in breast tumor progression. Since
      orthotopic human xenograft models of breast cancer are poorly metastatic to bone
      and experimental models bypass the formation of a primary tumor, however, the
      precise contribution of tumor-specific alphavbeta3 to the spontaneous metastasis
      of breast tumors from the mammary gland to bone remains unclear. METHODS: We used
      a syngeneic orthotopic model of spontaneous breast cancer metastasis to test
      whether exogenous expression of alphavbeta3 in a mammary carcinoma line (66cl4)
      that metastasizes to the lung, but not to bone, was sufficient to promote its
      spontaneous metastasis to bone from the mammary gland. The tumor burden in the
      spine and the lung following inoculation of alphavbeta3-expressing 66cl4
      (66cl4beta3) tumor cells or control 66cl4pBabe into the mammary gland was
      analyzed by real-time quantitative PCR. The ability of these cells to grow and
      form osteolytic lesions in bone was determined by histology and tartrate
      resistant acid phosphatase staining of bone sections following intratibial
      injection of tumor cells. The adhesive, migratory and invasive properties of
      66cl4pBabe and 66cl4beta3 cells were evaluated in standard in vitro assays.
      RESULTS: The 66cl4beta3 tumors showed a 20-fold increase in metastatic burden in
      the spine compared with 66cl4pBabe. A similar trend in lung metastasis was
      observed. alphavbeta3 did not increase the proliferation of 66cl4 cells in vitro
      or in the mammary gland in vivo. Similarly, alphavbeta3 is not required for the
      proliferation of 66cl4 cells in bone as both 66cl4pBabe and 66cl4beta3
      proliferated to the same extent when injected directly into the tibia. 66cl4beta3
      tumor growth in the tibia, however, increased osteoclast recruitment and bone
      resorption compared with 66cl4 tumors. Moreover, alphavbeta3 increased 66cl4
      tumor cell adhesion and alphavbeta3-dependent haptotactic migration towards bone
      matrix proteins, as well as their chemotactic response to bone-derived soluble
      factors in vitro. CONCLUSION: These results demonstrate for the first time that
      tumor-specific alphavbeta3 contributes to spontaneous metastasis of breast tumors
      to bone and suggest a critical role for this receptor in mediating chemotactic
      and haptotactic migration towards bone factors.

PMID- 16608537
TI  - The efficacy of Adeli suit treatment in children with cerebral palsy.

PMID- 16608538
TI  - Comparison of efficacy of Adeli suit and neurodevelopmental treatments in
      children with cerebral palsy.
AB  - This study compared the efficacy of Adeli suit treatment (AST) with
      neurodevelopmental treatment (NDT) in children with cerebral palsy (CP). Twenty
      four children with CP, Levels II to IV according to the Gross Motor Function
      Classification System (GMFCS), were matched by age and functional status and
      randomly assigned to the AST or NDT treatment groups. In the AST group (n=12;
      eight males, four females; mean age 8.3 y [SD 2.0]), six children had
      spastic/ataxic diplegia, one triplegia and five spastic/mixed quadriplegia. In
      the NDT group (n=12; nine males, three females; mean age 8.1 y [SD 2.2]), five
      children had spastic diplegia and seven had spastic/mixed quadriplegia. Both
      groups were treated for 4 weeks (2 hours daily, 5 days per week, 20 sessions). To
      compare treatments, the Gross Motor Function Measure (GMFM-66) and the mechanical
      efficiency index (EIHB) during stair-climbing were measured at baseline,
      immediately after 1 month of treatment, and 10 months after baseline. The small
      but significant time effects for GMFM-66 and EIHB that were noted after 1 month
      of both intensive physiotherapy courses were greater than expected from natural
      maturation of children with CP at this age. Improvements in motor skills and
      their retention 9 months after treatment were not significantly different between
      the two treatment modes. Post hoc analysis indicated a greater increase in EIHB
      after 1 month (p=0.16) and 10 months (p=0.004) in AST than that in NDT,
      predominantly in the children with higher motor function (GMFCS Levels II and
      III). The results suggest that AST might improve mechanical efficiency without a
      corresponding gain in gross motor skills, especially in children with higher
      levels of motor function.

PMID- 16608539
TI  - Social adjustment of children with cerebral palsy in mainstream classes: peer
      perception.
AB  - The aim of this study was to describe the social experience of children with
      cerebral palsy (CP) in mainstream classes in Canada and compare it with that of
      their classmates without disability. The CP group included 25 females and 35
      males (mean age 10 y 5 mo [SD 0.95], range 10 y 4 mo-10 y 10 mo) diagnosed as
      having hemiplegia (n=44) or diplegia (n=16) and classified as Level I on the
      Gross Motor Function Classification System (GMFCS). Fifty-seven comparison
      children, born at term and without any motor and/or sensory impairment, were
      recruited from the classes of the children with CP during a school visit (mean
      age 10 y 3 mo, [SD 1.0], range 10 y-10 y 6 mo). They were matched to children
      with CP for sex, age, parents' education level, and family income. Social
      adjustment measures (social status, reciprocated friendships, social isolation,
      aggression, sociability/leadership, and verbal and/or physical victimization)
      were obtained by conducting a class-wide sociometric interview (n=943) in the
      classes of the children with CP. Findings showed that children with CP
      (specifically females with CP and irrespective of their type of disability) had
      fewer reciprocated friendships, exhibited fewer sociable/leadership behaviours,
      and were more isolated and victimized by their peers than their classmates
      without a disability. This seems to suggest that females and males with CP are
      perceived differently from their peers in a mainstreaming context. The discussion
      addresses the issue of age- and sex-related differences and provides avenues of
      intervention relating to personal and environmental factors that could facilitate
      or interfere with the social experience of children with CP in a mainstream
      environment.

PMID- 16608540
TI  - Patterns of participation in recreational and leisure activities among children
      with complex physical disabilities.
AB  - Children with physical disabilities are at increased risk of limitations to
      participation in everyday activities. This study describes research examining the
      participation of children in day-to-day formal and informal activities (excluding
      mandated academic schooling). Using the Children's Assessment of Participation
      and Enjoyment (CAPE) measure, data on participation patterns were collected from
      427 children (229 males, 198 females; mean age 10 y [SD 2 y 4 mo]; range 6-14 y)
      with physical limitations and from their families. The primary types of physical
      disability in the sample included cerebral palsy, spina bifida, acquired brain
      injury, and musculoskeletal limitations. Findings indicate a broad range of
      diversity and intensity of participation, with proportionately greater
      involvement in informal rather than formal activities. Significant differences in
      participation and enjoyment were found between males and females, and for
      children more than 12 years of age. Children's participation was less diverse in
      families reporting lower income, single-parent status, and lower respondent
      parent education. These findings provide a foundation for an improved
      understanding of the participation of children with physical disabilities, which
      can assist families and service providers in planning activities that fit with
      their child's preferences and ensure active participation.

PMID- 16608541
TI  - Longitudinal use of the Child Health Questionnaire in childhood cerebral palsy.
AB  - This study sought to describe change and stability in health-related quality of
      life (HRQL) over time in a cross-section of children with cerebral palsy (CP)
      using the Child Health Questionnaire (CHQ) through repeated surveys of the
      children's parents/caregivers. A total of 177 children with CP (98 males, 79
      females); age range 3 to 18 years (mean age 8 y 6 mo, [SD 4 y 2 mo]; Gross Motor
      Function Classification System: Level I 40%, Level II 14%, Level III 14%, Level
      IV 16%, and Level V 17%) were enrolled as a convenience sample from the
      outpatient clinics at a tertiary-care children's hospital. The main outcome
      measure was HRQL as determined by the CHQ--Parent Form 50. Parents reported
      reduced HRQL for their children with CP relative to norms for the CHQ. Although
      Role--Physical functioning (reflecting how physical impairment interferes with
      daily activity) declined with time, all other subscales of the CHQ were stable
      over the course of 1 year. CHQ scores were not measurably affected by common
      medical interventions. Children with CP have lower CHQ scores than other children
      that are, on average, stable over the course of 1 year.

PMID- 16608542
TI  - Neurodevelopmental outcome of preterm infants with ventricular dilatation with
      and without associated haemorrhage.
AB  - This study investigated whether in preterm children who had ventricular
      dilatation (VD) on neonatal cranial ultrasound outcome at age 8 years was
      influenced by the additional presence of germinal matrix haemorrhage-
      intraventricular haemorrhage (GMH-IVH). Six-hundred and ninety-nine preterm
      infants (<33 wks' gestation, mean 29.6 wks [SD 2.1]) with either normal cranial
      ultrasound (n=616; 286 females, 330 males), or with VD with (n=66; 32 females, 34
      males) or without (n=17; 4 females, 13 males) GMH-IVH were enrolled in the study.
      At age 8 years outcome was assessed in 567 (81%) of the 699 children by
      neurological examination, the Test of Motor Impairment (TOMI), the test of Visuo
      Motor Integration (VMI), and the Wechsler Intelligence Scales for Children.
      Results showed that the proportion of children with disabling impairments was
      higher in the group with VD and GMH-IVH. Performance on TOMI and VMI (even in
      those without disabling impairments) was poorer in those with VD and GMH-IVH than
      in children with normal scans or those with VD only. Children with VD and GMH-IVH
      had significantly lower performance IQ than children with normal ultrasound,
      whereas those with VD only were not different from those with normal scans.
      Results suggest the presence of subtle white matter injury that has not been
      identified by neonatal cranial ultrasound. Although this study did not
      investigate biochemical markers of haemorrhage, we hypothesize that non-protein
      bound iron is likely to be a contributing factor to white matter damage in
      preterm infants.

PMID- 16608543
TI  - Medical, surgical, and health outcomes of gastrostomy feeding.
AB  - A prospective controlled study with repeated measures before and after surgery
      examined the medical, surgical, and health outcomes of gastrostomy for children
      with disabilities at a tertiary paediatric referral centre in the North Thames
      area, UK. Anthropometric measures included weight, mid-upper-arm and head
      circumference. Five-day prospective food diaries were completed and data on
      physical health and surgical outcomes recorded. Seventy-six children participated
      and underwent gastrostomy (44 males, 32 females; median age 3 y 4 mo, range 4 mo
      17 y 5 mo), and 35/76 required an anti-reflux procedure. Categories of disability
      were: cerebral palsy (32/76), syndrome of chromosomal or other genetic origin
      (25/76), slowly progressive degenerative disease (11/76), and unconfirmed
      diagnosis (8/76). Most children had gross motor difficulties (99%) and were non
      ambulant (83%). Oromotor problems were identified in 78% of children, 69%
      aspirated, and 65% were fed nasogastrically before surgery. The mean weight
      before surgery was -2.84 standard deviation score (SDS; SD 2.21, range -9.8 to
      3.4). Two-thirds of children achieved catch-up growth postoperatively: weight-for
      age (mean difference 0.51 SDS, 95% CI 0.23-0.79, p=0.001) and mid-upper arm
      circumference (mean difference 1.12 cm, 95% confidence interval 0.50-1.75,
      p=0.001). Health gains included a reduction in drooling, secretions, vomiting,
      and constipation. Major surgical complications were found in 13/74 children. The
      study provides evidence that catch-up growth and health gains are possible
      following gastrostomy.

PMID- 16608544
TI  - Neuropsychiatric and neurodevelopmental outcome of children at age 6 and 7 years
      who screened positive for language problems at 30 months.
AB  - We present a prospective study at school age of neuropsychiatric and
      neurodevelopmental outcome of language delay suspected at child health screening
      around 30 months of age. In a community sample, 25 children (21 males, 4 females)
      screening positive and 80 children (38 males, 42 females) screening negative for
      speech and language problems at age 30 months were examined in detail for
      language disorders at age 6 years. The screen-positive children were then
      followed for another year and underwent in-depth neuropsychiatric examination by
      assessors blind to the results of previous testing. Detailed follow-up results at
      age 7 years were available for 21 children. Thirteen of these 21 children (62%)
      had a major neuropsychiatric diagnosis (autism, atypical autism, Asperger's
      syndrome, attention-deficit-hyperactivity disorder [ADHD]), or combinations of
      these. Two further children (10%) had borderline IQ with no other major
      diagnosis. We conclude that children in the general population who screen
      positive for speech and language problems before age 3 years appear to be at very
      high risk of autism spectrum disorders or ADHD, or both, at 7 years of age.
      Remaining language problems at age 6 years strongly predict the presence of
      neuropsychiatric or neurodevelopmental disorders at age 7 years.

PMID- 16608545
TI  - Early motor development and later language and reading skills in children at risk
      of familial dyslexia.
AB  - Relationships between early motor development and language and reading skills
      were studied in 154 children, of whom 75 had familial risk of dyslexia (37
      females, 38 males; at-risk group) and 79 constituted a control group (32 females,
      47 males). Motor development was assessed by a structured parental questionnaire
      during the child's first year of life. Vocabulary and inflectional morphology
      skills were used as early indicators of language skills at 3 years 6 months and 5
      years or 5 years 6 months of age, and reading speed was used as a later indicator
      of reading skills at 7 years of age. The same subgroups as in our earlier study
      (in which the cluster analysis was described) were used in this study. The three
      subgroups of the control group were 'fast motor development', 'slow fine motor
      development', and 'slow gross motor development', and the two subgroups of the at
      risk group were 'slow motor development' and 'fast motor development'. A
      significant difference was found between the development of expressive language
      skills. Children with familial risk of dyslexia and slow motor development had a
      smaller vocabulary with poorer inflectional skills than the other children. They
      were also slower in their reading speed at the end of the first grade at the age
      of 7 years. Two different associations are discussed, namely the connection
      between early motor development and language development, and the connection
      between early motor development and reading speed.

PMID- 16608546
TI  - Interobserver reliability of visual interpretation of electroencephalograms in
      children with newly diagnosed seizures.
AB  - The reliability of visual interpretation of electroencephalograms (EEG) is of
      great importance in assessing the value of this diagnostic tool. We prospectively
      obtained 50 standard EEGs and 61 EEGs after partial sleep deprivation from 93
      children (56 males, 37 females) with a mean age of 6 years 10 months (SE 5 mo;
      range 4 mo-15 y 7 mo) with one or more newly diagnosed, unprovoked seizures. Two
      clinical neurophysiologists independently classified the background pattern and
      the presence of epileptiform discharges or focal non-epileptiform abnormalities
      of each EEG. The agreement was substantial for the interpretation of the EEG as
      normal or abnormal (kappa 0.66), almost perfect for the presence of epileptiform
      discharges (kappa 0.83), substantial for the occurrence of an abnormal background
      pattern (kappa 0.73), and moderate for the presence of focal non-epileptiform
      discharges (kappa 0.54). In conclusion, the reliability of the visual
      interpretation of EEGs in children is almost perfect as regards the presence of
      epileptiform abnormalities, and moderate to substantial for the presence of other
      abnormalities.

PMID- 16608547
TI  - Specific memory impairment in a multiple disabled male with fragile X syndrome
      and temporal lobe epilepsy.
AB  - Evaluation of the cognitive repercussions of an epileptic disorder and its
      treatment are important issues in clinical follow-up. This especially holds true
      for temporal lobe epilepsy (TLE) where resective surgery can be a valid treatment
      option. However, in patients where TLE coexists with another neurocognitive
      disorder, questions can arise about the precise nature of the neuropsychological
      deficits. The aim of the present study was to evaluate memory impairments, found
      in a male aged 12 years who had the dual pathology of fragile X syndrome and
      refractory TLE. Memory functions of this child were compared with those of a male
      aged 11 years 7 months with fragile X syndrome matched for intellectual
      functioning as indicated by highly comparable verbal (5 y 5 mo vs 5 y 9 mo) and
      non-verbal (7 y 2 mo vs 6 y 1 mo) cognitive age equivalents. Performance on each
      neuropsychological measure was evaluated twice, separately with normative data
      based on chronological age and on verbal or non-verbal cognitive level. A
      specific, distinguishable profile of task performance could be found only when
      controlling for general level of cognitive functioning. This made it possible to
      accurately evaluate neuropsychological abilities before and 6 months after
      anterior temporal lobe resection even in this male with a complex neurological
      pathology.

PMID- 16608548
TI  - Atypical clinical course in juvenile metachromatic leukodystrophy involving novel
      arylsulfatase A gene mutations.
AB  - A male and female with juvenile metachromatic leukodystrophy (MLD) with unusual
      manifestations are presented, each involving a novel arylsulfatase A gene
      mutation. One patient demonstrated acute intermittent encephalopathic episodes
      for 1 year after having received the diagnosis of MLD at the age of 6 years. The
      other patient presented at the age of 5 years with acute hemiparesis, which was
      diagnosed as acute disseminated encephalomyelitis and resolved in 3 weeks. After
      2 years of remission he started to show progressive neurological deterioration.
      The episodic manifestations in both patients were associated with acute,
      resolving cerebral lesions on magnetic resonance imaging accompanying or
      preceding the classical demyelinating lesions of MLD. The diagnosis of MLD was
      based on arylsulfatase A enzyme activity levels and genetic analysis, and after
      the exclusion of neurological conditions such as encephalitis, vasculopathy, or
      mitochondrial disorders. The pathogenesis of this previously undescribed finding
      in MLD is unknown but might be related to a susceptibility of myelin to acute
      damage.

PMID- 16608549
TI  - Prolonged coexistence of transient and permanent circuitry elements in the
      developing cerebral cortex of fetuses and preterm infants.
AB  - The aim of this paper is to evaluate correlative magnetic resonance imaging (MRI)
      and histological parameters of development of cortical afferents during
      pathfinding and target selection in transient fetal cerebral laminas in human
      fetuses and preterm infants. The transient fetal subplate zone, situated between
      the fetal white matter (i.e. intermediate zone) and the cortical plate, is the
      crucial laminar compartment for development of thalamocortical and
      corticocortical afferents. The prolonged coexistence of transient (endogenously
      active) and permanent (sensory-driven) circuitry within the transient fetal zones
      is a salient feature of the fetal and preterm cortex; this transient circuitry is
      the substrate of cerebral functions in preterm infants. Another transient aspect
      of organization of developing fibre pathways is the abundance of extracellular
      matrix and guidance molecules in periventricular crossroads of projection and
      corticocortical pathways. Both the subplate zone and periventricular crossroads
      are visible on MRI in vivo and in vitro. Hypoxic-ischaemic lesions of
      periventricular crossroads are the substrate for motor, sensory, and cognitive
      deficits after focal periventricular leukomalacia (PVL). Lesions of distal
      portions of the white matter and the subplate zone are the substrate for diffuse
      PVL. The neuronal elements in transient fetal zones form a developmental
      potential for plasticity after perinatal cerebral lesions.

PMID- 16608550
TI  - Aggravation of epilepsy by anti-epileptic drugs.
AB  - The possibility that so-called anti-epileptic drugs (AEDs) may aggravate epilepsy
      must always be borne in mind by the clinician. Many reports of such aggravation
      of seizures have been published. Most such reports are anecdotal and speculative,
      and suggest that many such reactions are idiosyncratic. However, for some there
      is a sufficient body of evidence to suggest that some AEDs used in certain
      epilepsies may consistently cause worsening of seizures. Seizure aggravation may
      include increase in the frequency or severity of existing seizures, emergence of
      new types of seizure, or the occurrence of status epilepticus. The
      pathophysiology of seizure aggravation is poorly understood including non
      specific effects such as those associated with sedation, drug-induced
      encephalopathy, and paradoxical or inverse pharmacodynamic effects. For some
      epilepsies the choice of AEDs may be inappropriate, and although the mechanism of
      seizure aggravation is not clear, its occurrence may be fairly predictable. This
      is best documented for the use of carbamazepine in idiopathic generalized and
      myoclonic epilepsies. Most other AEDs have been reported occasionally to cause
      seizure aggravation. The lowest risk of seizure aggravation appears to be with
      valproate. Risk factors for worsening of seizures are epileptic encephalopathy,
      polytherapy, high frequency of seizures, and cognitive impairment. Advances in
      pharmacogenomics may in the future enable such adverse effects to be predicted
      for individual patients. Meanwhile, a systematic approach to reporting AED
      induced seizure aggravation should be developed.

PMID- 16608552
TI  - Botulinum toxin and cerebral palsy: time for reflection?

PMID- 16608553
TI  - Aspiration of peritonsillar abscess in severe trismus.
AB  - We present a novel method of aspirating a peritonsillar abscess in a patient with
      severe trismus. In our experience, this method is efficient, allows good access
      to the peritonsillar area and facilitates rapid resolution of the trismus before
      definitive drainage can be performed.

PMID- 16608554
TI  - Relationship between tumour-node-metastasis stage of laryngeal squamous cell
      carcinoma and duration of symptoms.
AB  - OBJECTIVE: To evaluate the relationship between disease stage and duration of
      symptoms for squamous cell carcinoma of the larynx. METHOD: We evaluated
      retrospectively data from 102 laryngeal squamous cell carcinoma patients seen in
      the otorhinolaryngology department of the Gazi University School of Medicine
      between December 1996 and June 2004. Inclusion criteria were a histologic
      diagnosis of laryngeal squamous cell carcinoma, no previous medical, surgical or
      radiological treatment for carcinoma, and the absence of any other primary
      tumours or distant metastatic disease. RESULTS: There was no relationship between
      duration of symptoms and stage of the disease, both for glottic and supraglottic
      tumours. When glottic and supraglottic tumours were compared, no significant
      difference in symptom duration could be found. CONCLUSION: There is no
      correlation between symptom duration and the stage of the disease for squamous
      cell carcinoma of the larynx. Therefore, symptom duration does not reflect the
      stage of the tumour.

PMID- 16608555
TI  - New insights into the functions of anthrax toxin.
AB  - Anthrax is the disease caused by the Gram-positive bacterium Bacillus anthracis.
      Two toxins secreted by B. anthracis - lethal toxin (LT) and oedema toxin (OT) -
      contribute significantly to virulence. Although these toxins have been studied
      for half a century, recent evidence indicates that LT and OT have several roles
      during infection not previously ascribed to them. Research on toxin-induced
      effects other than cytolysis of target cells has revealed that LT and OT
      influence cell types previously thought to be insensitive to toxin. Multiple host
      factors that confer sensitivity to anthrax toxin have been identified recently,
      and evidence indicates that the toxins probably contribute to colonisation and
      invasion of the host. Additionally, the toxins are now known to cause a wide
      spectrum of tissue and organ pathophysiologies associated with anthrax. Taken
      together, these new findings indicate that anthrax-toxin-associated pathogenesis
      is much more complex than has been traditionally recognised.

PMID- 16608557
TI  - Does co-morbid depressive illness magnify the impact of chronic physical illness?
      A population-based perspective.
AB  - OBJECTIVE: To examine the relative and combined impact of depressive and chronic
      physical conditions on functional status and health-care use in the general
      population. METHOD: Canadian, representative, population-based cross-sectional
      survey (n=130,880). Major depressive disorder (MDD) in the past 12 months was
      assessed by structured interview, and physical disorders, activity reduction,
      role impairment and work absence by self-report. The relative impact of MDD and
      six common chronic physical illnesses (asthma, arthritis, back problems, chronic
      obstructive pulmonary disease, heart disease and diabetes) was estimated using
      multivariate regression, adjusting for sociodemographic characteristics and
      overall chronic physical illness burden. RESULTS: After adjusting for
      sociodemographic characteristics, alcohol dependence and chronic physical illness
      burden, the presence of co-morbid MDD was associated with significantly greater
      (approximately double the) likelihood of health-care utilization and increased
      functional disability and work absence compared to the presence of a chronic
      physical illness without co-morbid MDD. This impact of MDD was seen across each
      of the six chronic physical illnesses examined in this study, with the strongest
      associations seen for work absence. CONCLUSIONS: These observations confirm prior
      findings of a strong association at the population level between major depression
      and health-care use and role impairment among persons with chronic physical
      disorders. They also point to the significant impact of co-morbid major
      depression on health-care seeking, disability and work absence in persons with
      chronic physical illness, underscoring the need for greater efforts to design and
      test the impact of detection and treatment programs for such individuals.

PMID- 16608558
TI  - Levels-of-processing effect on internal source monitoring in schizophrenia.
AB  - BACKGROUND: Recognition can be normalized in schizophrenia by providing patients
      with semantic organizational strategies through a levels-of-processing (LOP)
      framework. However, patients may rely primarily on familiarity effects, making
      recognition less sensitive than source monitoring to the strength of the episodic
      memory trace. The current study investigates whether providing semantic
      organizational strategies can also normalize patients' internal source-monitoring
      performance. METHOD: Sixteen clinically stable medicated patients with
      schizophrenia and 15 demographically matched healthy controls were asked to
      identify the source of remembered words following an LOP-encoding paradigm in
      which they alternated between processing words on a 'shallow' perceptual versus a
      'deep' semantic level. A multinomial analysis provided orthogonal measures of
      item recognition and source discrimination, and bootstrapping generated variance
      to allow for parametric analyses. LOP and group effects were tested by
      contrasting recognition and source-monitoring parameters for words that had been
      encoded during deep versus shallow processing conditions. RESULTS: As in a
      previous study there were no group differences in LOP effects on recognition
      performance, with patients and controls benefiting equally from deep versus
      shallow processing. Although there were no group differences in internal source
      monitoring, only controls had significantly better performance for words
      processed during the deep encoding condition. Patient performance did not
      correlate with clinical symptoms or medication dose. CONCLUSIONS: Providing a
      deep processing semantic encoding strategy significantly improved patients'
      recognition performance only. The lack of a significant LOP effect on internal
      source monitoring in patients may reflect subtle problems in the relational
      binding of semantic information that are independent of strategic memory
      processes.

PMID- 16608559
TI  - Effect of body-oriented psychological therapy on negative symptoms in
      schizophrenia: a randomized controlled trial.
AB  - BACKGROUND: In order to improve the treatment of medication-resistant negative
      symptoms in schizophrenia, new interventions are needed. Neuropsychological
      considerations and older reports in the literature point towards a potential
      benefit of body-oriented psychological therapy (BPT). This is the first
      randomized controlled trial specifically designed to test the effectiveness of
      manualized BPT on negative symptoms in chronic schizophrenia. METHOD: Out
      patients with DSM-IV continuous schizophrenia were randomly allocated to either
      BPT (n=24) or supportive counseling (SC, n=21). Both therapies were administered
      in small groups in addition to treatment as usual (20 sessions over 10 weeks).
      Changes in negative symptom scores on the Positive and Negative Symptom Scale
      (PANSS) between baseline, post-treatment and 4-month follow-up were taken as
      primary outcome criteria in an intention-to-treat analysis. RESULTS: Patients
      receiving BPT attended more sessions and had significantly lower negative symptom
      scores after treatment (PANSS negative, blunted affect, motor retardation). The
      differences held true at 4-month follow-up. Other aspects of psychopathology and
      subjective quality of life did not change significantly in either group.
      Treatment satisfaction and ratings of the therapeutic relationship were similar
      in both groups. CONCLUSIONS: BPT may be an effective treatment for negative
      symptoms in patients with chronic schizophrenia. The findings should merit
      further trials with larger sample sizes and detailed studies to explore the
      therapeutic mechanisms involved.

PMID- 16608560
TI  - Concordance in the mental health of spouses: analysis of a large national
      household panel survey.
AB  - BACKGROUND: Spousal concordance for common mental disorders provides evidence of
      the relevance of social contextual factors. There are, however, limitations
      within the existing literature examining spousal similarity in mental health and
      little consensus as to the causes of spousal similarity. This study considers a
      large representative sample and examines an extensive range of risk factors using
      multilevel statistical methods to explore spousal similarity in common mental
      disorders. METHOD: Data were from the Household, Income and Labour Dynamics in
      Australia (HILDA) Survey, a large nationally representative survey of Australian
      households. Analysis focused on 3808 mixed-sex couples in marriage and de facto
      relationships. Multilevel models assessed the mental health scale of the SF-36.
      Analyses considered risk factors at the individual, couple and area levels,
      examined the effects of relationship duration on concordance, and considered
      longitudinal data to assess the consistency with cross-sectional analysis.
      RESULTS: Significant spousal concordance on the mental health scale was
      demonstrated (r=0.25) and was independent of, and unexplained by mental health
      risk factors, including experience of multiple shared life events. Spousal
      similarity for mental health increased across the first 5 years of relationships.
      CONCLUSIONS: Evidence of spousal concordance for common mental disorders
      highlights the importance of the social context of marriage in the aetiology of
      mental illness and identifies an important direction for further research.

PMID- 16608563
TI  - Sample analysis with miniaturized plasmas.

PMID- 16608564
TI  - Abel inversion applied to a small set of emission data from a microwave plasma.
AB  - In this work we propose a criterion to apply the Abel inversion in the case of a
      small set of experimental data to be used in laboratory plasmas. The Nestor-Olsen
      method, spline interpolation, and Fourier transform Abel inversion have been
      compared in order to study the influence of statistical noise and the number of
      sampled data. The application of this criterion permits us to obtain a radial
      distribution of the plasma parameters (densities and temperatures) from the
      spectral line profiles emitted by the discharge. The proposed criterion has been
      tested using the lateral intensities of several lines emitted by a microwave
      helium plasma column generated at atmospheric pressure.

PMID- 16608565
TI  - Laser-induced breakdown spectroscopy for ambient air particulate monitoring:
      correlation of total and speciated aerosol particle counts.
AB  - A statistical analysis of ambient air particle monitoring, namely PM2.5, is
      presented to elucidate the correlations between laser-induced breakdown
      spectroscopy (LIBS)-based speciated aerosol monitoring and non-speciated aerosol
      monitoring (i.e., total particle counts). LIBS was used in a real-time,
      conditional-processing mode to identify individual aerosol particles containing
      detectable quantities of either calcium or sodium, as based on the resulting
      atomic emission signals. Using this technique, real-time measurements of
      speciated aerosol particle concentrations and analyte mass concentrations were
      evaluated for a total of 60 1-hour sampling periods spread over a 5-week period.
      For each 1-hour sampling period, total aerosol counts were simultaneously
      monitored using a commercial light scattering-based instrument. Over the 30
      sampling periods, aerosol counts (both total and LIBS-based) were found to vary
      by more than one order of magnitude. For aerosol particles in the 500 nm to 2.5
      microm size range, significant correlations were found between the two sampling
      methods, resulting in correlation coefficients (r2) ranging from 0.22 to 0.93. In
      addition, transient fluctuations in aerosol counts on a timescale of 5 to 10
      minutes were successfully observed simultaneously with the two monitoring
      techniques, thereby demonstrating the temporal resolution of LIBS.

PMID- 16608566
TI  - Assessment of multiphoton absorption in inert gases for the measurement of gas
      temperatures.
AB  - A spatially resolved optical technique to measure gas temperature was assessed.
      The technique relies on multiphoton absorption in inert gases. In contrast to
      laser-induced fluorescence, absorption is insensitive to collisional
      deactivation, and, in contrast to one-photon absorption, multiphoton absorption
      only occurs around the focus point of a typical laser beam. Multiphoton
      absorption features both the merits of being insensitive to quenching and of
      being a spatially resolved technique. In a case study we assessed two-photon
      absorption in xenon upon exciting the 5p6 1S0-->5p56p[5/2]2 transition in xenon
      at a wavelength of 256 nm. The amount of light absorbed by xenon is related to
      the number density of the gas, and if the gas pressure is known then the gas
      temperature can be inferred from the number density. Two-photon absorbance was
      measured as a function of xenon number density and was used to validate a
      theoretical model of the absorption process. We discuss the circumnavigation of
      experimental challenges in applying this technique and analyze its precision in
      terms of the inferred gas temperature.

PMID- 16608567
TI  - Quantitative vapor-phase infrared spectrometry of ammonia.
AB  - Reference spectra of ammonia from four sources are compared. Low-resolution
      spectra (i.e., spectra for which the spectrometer resolution is numerically
      greater than the full-width at half-height of the rotational lines) were obtained
      from the Environmental Protection Agency (EPA) web site and from Infrared
      Analysis, Inc. High-resolution (0.12 cm-1) spectra were obtained from the
      National Institute for Standards and Technology (NIST) and Pacific Northwest
      National Laboratory (PNNL). Two protocols were used to validate the EPA and
      Infrared Analysis spectra, with one requiring that Beer's law be obeyed by the
      low-resolution spectrum and the other that Beer's law be obeyed by the high
      resolution spectrum. In all cases, the second protocol gave a significantly
      better spectral match. It is shown that the path-integrated concentrations for
      the low-resolution reference spectra were in error by as little as 4% to as much
      as an order of magnitude, presumably because of the effect of adsorption on the
      cell walls. Measured absorptivities of the NIST and PNNL spectra were different
      by approximately 2.6% and it is believed that the effect of adsorption on these
      spectra is small. When the same protocols were used to test the reference
      spectrum of methane, the calculated path-integrated concentration was only
      approximately 2% different from the one that was calculated from the NIST
      reference spectrum, suggesting that the data processing protocols provide
      accurate data.

PMID- 16608568
TI  - Water-vapor detection using asynchronous THz sampling.
AB  - The use of a fiber-coupled terahertz (THz) transmitter/receiver pair for
      spectroscopic detection of water vapor is investigated. Transmission signals of
      an alumina cylinder demonstrate that the measurement approach can be applied in a
      windowless ceramic combustor. First, a conventional commercial
      transmitter/receiver pair is used to make measurements for frequencies to 1.25
      THz. Water-vapor absorption is clearly evident within the alumina transparency
      window and is readily modeled using existing databases. A variety of data
      acquisition schemes is possible using THz instrumentation. To assess signal
      collection techniques, a prototype THz transmitter/receiver pair is then used
      with the asynchronous optical-sampling (ASOPS) technique to obtain asynchronous
      THz-sampling signals to 1 THz without the need for an optomechanical delay line.
      Two mode-locked Ti:sapphire lasers operating at slightly different repetition
      rates are used for pumping the transmitter and receiver independently to permit a
      complete time-domain THz signal to be recorded. The resulting repetitive phase
      walkout is demonstrated by collecting power spectra of room air that exhibit
      water-vapor absorption.

PMID- 16608569
TI  - Characterization of a mid-infrared hollow waveguide gas cell for the analysis of
      carbon monoxide and nitric oxide.
AB  - Infrared spectroscopy is commonly applied to the analysis of small gas-phase
      molecules. One of the limitations of using Fourier transform infrared (FT-IR)
      spectroscopy for these applications is the time response of long path length gas
      cells. Hollow waveguides (HW) that transmit in the mid-infrared spectral range
      have higher optical efficiencies compared to long path length cells due to
      smaller cell volumes. This study characterizes a silver coated, 2 mm inner
      diameter HW for the analysis of carbon monoxide (CO) and nitric oxide (NO) and
      compares the performance to a 3 m gas cell and traditional gas analyzers. The HW
      was found to have a CO response time less than the NDIR analyzer and
      approximately one-tenth of the response time on the FT-IR system equipped with a
      3 m gas cell. The utility of the increased response time was demonstrated by
      measuring CO concentrations in sidestream cigarette smoke at the same temporal
      resolution as an NDIR analyzer. A 10 to 60% increase in sensitivity using various
      frequencies for both CO and NO was observed using the HW compared to the 3 m
      multipass gas cell. However, cost savings for gas-sensing applications can be
      achieved on a per analyte basis by using FT-IR spectroscopy, especially in
      combination with a HW gas-sensing module, which is significantly less expensive
      than a multipass gas cell.

PMID- 16608570
TI  - Real-time fourier transform-infrared analysis of carbon monoxide and nitric oxide
      in sidestream cigarette smoke.
AB  - Fourier transform infrared (FT-IR) spectroscopy was compared directly to
      independent standard analytical techniques for the routine measurement of carbon
      monoxide (CO) and nitric oxide (NO) yields from cigarette sidestream smoke. The
      FT-IR instrument was configured in-line with a nondispersive infrared (NDIR)
      analyzer for CO analysis and a chemiluminescence (CL) analyzer for NO analysis to
      monitor the sidestream smoke from a single port of a linear smoking machine. A
      cold trap was inserted prior to the FT-IR to minimize the levels of vapor phase
      interferents, such as water. Univariate and multivariate regression analysis were
      evaluated for the prediction of cigarette yield from time-resolved spectral data
      at 1, 2, 4 and 8 cm-1 spectral resolution. Regressions were developed using three
      different spectral ranges including unique rotation-vibration lines, the R
      branch, and the entire absorption band. As per standard methods, yields were
      calculated from the concentration traces generated during the smoke runs for five
      different cigarettes spanning the expected range of mainstream total particulate
      matter deliveries. The FT-IR traces for the smoke runs revealed improved temporal
      resolution yielding analytical information from smoke generated in between puffs.
      The performance between the validation methods and the FT-IR calibrations was
      statistically compared. In general, for the determination of CO, the FT-IR
      calibrations underestimated the yield measured by NDIR by less than 10%. For the
      NO measurement, the univariate FT-IR calibrations overestimated the NO yield
      measured by the CL analyzer, whereas the partial least squares (PLS) calibrations
      showed good agreement. PLS calibrations were developed for both analytes
      providing no significant difference when compared to the respective standard
      analytical techniques. Results for sidestream CO and NO yields for Kentucky
      reference cigarette 1R4F utilizing 8 cm-1 calibrations compared favorably to
      values reported elsewhere in the literature. Hence, calibration of the FT-IR
      system at 8 cm-1 spectral resolution clearly revealed the potential of this
      method, providing enhanced temporal resolution, simultaneous determination of
      several smoke components, and reduced complexity of the experimental setup in
      contrast to the standard techniques.

PMID- 16608571
TI  - Infrared and Raman spectroscopy study of alkyl hydroxamic acid and alkyl
      hydroxamate isomers.
AB  - The isomeric structures of alkyl hydroxamic acid, as well as its potassium salt,
      sodium salt, and an alcohol complex, have been characterized in the solid,
      liquid, and gaseous states by Fourier transform infrared (FT-IR) and FT-Raman
      spectroscopy. Raman spectroscopy provides insight into the long-standing debate
      over the isomeric composition of hydroxamates in the solid state and in an
      aqueous basic solution. IR and Raman results are not consistent with the enol
      isomer existing in the solid or liquid states of octyl or decyl hydroxamic acid,
      potassium hydroxamate, and sodium hydroxamate. The infrared and Raman spectra of
      these compounds provide clear and convincing evidence regarding their chemical
      structure, mainly from amide-type carbonyl, NH bending, and OH/NH stretching
      bands. Vibrational spectroscopy is sensitive to polar (FT-IR) and non-polar (FT
      Raman) vibrations and the influence of ionic and hydrogen bonding on these
      vibrations, and these abilities are particularly useful for characterizing keto
      versus enol and trans versus cis conformations in alkyl hydroxamic acid and its
      salts. Evolved gas analysis (EGA) in a nitrogen gas environment of alkyl
      hydroxamic acid and its salts is also discussed. EGA data reveal that water is
      not incorporated into the solid-state crystal structure of alkyl hydroxamic acid
      or the potassium salt; however, the sodium salt form is found to have a stable
      hydrate conformer that is shown to affect the Z isomer (NH trans to carbonyl, OH
      cis to carbonyl) IR absorbance bands. EGA data also indicates results that could
      be of interest to bio-pharmaceutical applications involving nitric oxide
      donation.

PMID- 16608572
TI  - Optimization of the rolling-circle filter for Raman background subtraction.
AB  - A procedure is proposed to optimize a high-pass filter enabling one to subtract
      the broadband background signals inherent in Raman spectra. A spectral approach
      is used to analyze the characteristics of the filter and the distortions in the
      processed spectra. Examples of the processing of real spectra are presented.

PMID- 16608573
TI  - On the use of band-target entropy minimization to simplify the interpretation of
      two-dimensional correlation spectroscopy.
AB  - Two-dimensional (2D) correlation spectroscopy has been extensively applied to
      analyze various vibrational spectroscopic data, especially infrared and Raman.
      However, when it is applied to real-world experimental data, which often contains
      various imperfections (such as noise interference, baseline fluctuations, and
      band-shifting) and highly overlapping bands, many artifacts and misleading
      features in synchronous and asynchronous maps will emerge, and this will lead to
      difficulties with interpretation. Therefore, an approach that counters many
      artifacts and therefore leads to simplified interpretation of 2D correlation
      analysis is certainly useful. In the present contribution, band-target entropy
      minimization (BTEM) is employed as a spectral pretreatment to handle many of the
      artifact problems before the application of 2D correlation analysis. BTEM is
      employed to elucidate the pure component spectra of mixtures and their
      corresponding concentration profiles. Two alternate forms of analysis result. In
      the first, the normally vxv problem is converted to an equivalent nvxnv problem,
      where n represents the number of species present. In the second, the pure
      component spectra are transformed into simple distributions, and an equivalent
      and less computationally intensive nv'xnv' problem results (v'<v). In both cases,
      the separation of spectral contributions greatly simplifies interpretation of the
      2D plots. This new approach is successfully applied to a solvent evaporation
      study where in situ Fourier transform infrared (FT-IR) spectroscopy is used as
      the analytical tool.

PMID- 16608574
TI  - Prediction of source rock origin by chemometric analysis of fourier transform
      infrared-attenuated total reflectance spectra of oil petroleum: evaluation of
      aliphatic and aromatic fractions by self-modeling mixture analysis.
AB  - This study describes a new methodology for the interpretation of Fourier
      transform infrared (FT-IR) attenuated total reflectance (ATR) spectra of
      Algerian, Brazilian, and Venezuelan crude oils. It is based on a comparative
      study between a chemometric treatment and the classical one, which refers to
      indices calculation. In fact, the combined use of FT-IR indices and principal
      component analysis (PCA) has led to the classification of the studied samples in
      terms of geographic distribution. Quantitative analysis has been successfully
      realized by the supervised method partial least squares (PLS), which has
      permitted the prediction of the locations of oils. We have also applied another
      mathematical processing method, simple-to-use interactive self-modeling mixture
      analysis (SIMPLISMA), to evaluate the aromatic and aliphatic composition of the
      oils by extracting pure spectra representative of the different fractions.

PMID- 16608575
TI  - Physics-based multiplicative scatter correction approaches for improving the
      performance of calibration models.
AB  - Light scattering effects pose a major problem in the estimation of chemical
      properties of particulate systems such as blood, tissue, and pharmaceutical
      solids. Recently, Martens et al. proposed an extended multiplicative signal
      correction (EMSC) approach where light-scattering effects were taken into account
      in an empirical manner. It is possible to include causal, first-principles
      mathematical models based on the physics of light scattering into the EMSC
      framework. This could lead to significant improvements in the separation of
      absorption and scattering effects. A preconditioning step prior to application of
      EMSC, whereby a transformation based on the physics of light scattering is used
      to convert the spectra into a form where the absorption and scattering effects
      are separable (an underlying assumption of EMSC), is proposed. Results indicate
      that the transformation followed by EMSC gives better calibration models than the
      direct application of EMSC to the absorbance spectra.

PMID- 16608576
TI  - Second-order calibration of excitation-emission matrix fluorescence spectra for
      the determination of N-phenylanthranilic acid derivatives.
AB  - A spectrofluorimetric method has been developed for the quantitative
      determination of mefenamic, flufenamic, and meclofenamic acids in urine samples.
      The method is based on second-order data multivariate calibration (unfolded
      partial least squares (unfolded-PLS), multi-way PLS (N-PLS), parallel factor
      analysis (PARAFAC), self-weighted alternating trilinear decomposition (SWATLD),
      and bilinear least squares (BLLS)). The analytes were extracted from the urine
      samples in chloroform prior to the determination. The chloroform extraction was
      optimized for each analyte, studying the agitation time and the extraction pH,
      and the optimum values were 10 minutes and pH 3.5, respectively. The
      concentration ranges in chloroform solution of each of the analytes, used to
      construct the calibration matrix, were selected in the ranges from 0.15 to 0.8
      microg mL-1 for flufenamic and meclofenamic acids and from 0.25 to 3.0 microg mL
      1 for mefenamic acid. The combination of chloroform extraction and second-order
      calibration methods, using the excitation-emission matrices (EEMs) of the three
      analytes as analytical signals, allowed their simultaneous determination in human
      urine samples, in the range of approximately 80 mg L-1 to 250 mg L-1, with
      satisfactory results for all the assayed methods. Improved results over unfolded
      PLS and N-PLS were found with PARAFAC, SWATLD, and BLLS, methods that exploit the
      second-order advantage.

PMID- 16608577
TI  - Direct determination of zinc in steel samples by electrothermal vaporization
      inductively coupled plasma atomic emission spectrometry.

PMID- 16608578
TI  - Use of Raman spectroscopy and multivariate classification techniques for the
      differentiation of fingernails and toenails.

PMID- 16608579
TI  - The changing role of general practitioners: how typical is the Dutch case?

PMID- 16608580
TI  - Values underlying the National Service Framework for coronary heart disease in
      England: a discourse analysis.
AB  - OBJECTIVES: The National Service Framework (NSF) for Coronary Heart Disease-
      published by the English Department of Health in 2000--sets out how those within
      the health service should seek to prevent and treat coronary heart disease and
      care for people with the disease. Its prescriptions are partly based on what is
      known about coronary heart disease and partly on its underlying 'values'. This
      paper seeks to identify those values. METHODS: An analysis of the discourses
      within the text of the NSF based on critical discourse analysis. RESULTS: Three
      different discourses can be identified: the managerial, the clinical and the
      political. The managerial discourse is dominant. Each discourse has its own
      values. The main 'aspirational' values within the NSF are efficiency,
      effectiveness, autonomy (choice), universalism and equity. Some aspirational
      values--particularly equity--appear to be largely rhetorical and lead to few
      recommendations or prescriptions. Some values that might have been expected to
      underlie the framework, such as compassion and democracy, are largely absent.
      CONCLUSIONS: Discourse analysis provides a more systematic and transparent method
      of describing the values behind health care policy than the methods that have
      been used previously.

PMID- 16608581
TI  - Another way to look at high service utilization: the contribution of disability.
AB  - OBJECTIVES: High users of health services are usually identified in terms of
      their health complications stemming from the coincidence of a number of chronic
      conditions. Instead, this analysis attempts to characterize high users in terms
      of disability, based on the belief that disability provides a more detailed and
      accurate representation of functional needs and health consequences. The study
      compares the characteristics of high users of health services among Canadian
      adults (aged 20-65) with those of low to moderate users and non-users. METHODS:
      Secondary analysis of data collected for the National Population Health Survey, a
      cross-sectional public-use population-based national survey, conducted in 1998
      99. RESULTS: No matter how disability is conceptualized and measured, it has the
      strongest association of all the variables considered with health service
      utilization. Whether looking at the simple presence of a disability or at
      specific impairments or activity restrictions, there is at least a two-fold
      increase in the risk of high use over the non-disabled. CONCLUSIONS: The present
      study challenges the clinical wisdom that high users should be the target for
      efforts to reduce the overall consumption of health services. Many high users
      consume on the basis, not of choice, but of need rooted in disability. Moreover,
      when compared with low or moderate service users, their clinical condition is
      exacerbated by social factors, including lower income, less education and less
      immediate family support. Equity cannot be achieved by focusing on reducing
      consumption by this clinically and socially vulnerable group.

PMID- 16608582
TI  - 'I suppose that depends on how I was feeling at the time': perspectives on
      questionnaires measuring quality of life and musculoskeletal pain.
AB  - OBJECTIVES: This study aimed to investigate the thoughts and reasoning of
      respondents in relation to their experience of back and knee pain while they were
      completing validated health status questionnaires as part of two epidemiological
      surveys. METHODS: Qualitative interviews with 10 participants who were sampled
      from previous questionnaire responders. Content analysis identified emerging
      themes. Analysis allowed for a comparison with other research, for a focus on
      disease-specific questionnaire interpretations, and use of additional survey
      material (i.e. annotations alongside questionnaire items and accompanying
      letters). RESULTS: Adaptation to limitations and comparisons with previous self
      and/or others changed the way people responded to the standardized questions. The
      determination of specific periods of pain proved very difficult for respondents
      because pain, and low back pain in particular, was rarely experienced as a stable
      phenomenon. In addition, the time frames used in questionnaires were often at
      variance with the lived reality of pain and its effects on individuals'
      perceptions of time. Respondents tended to emphasize the context within which
      they experienced pain, and in the case of knee pain, often ranked this pain in
      relation to other health issues. CONCLUSIONS: In epidemiological studies,
      differences in interpretations are averaged across large samples, but we argue
      that a deeper understanding of the range of individual interpretations is
      important if one is to acknowledge the different meanings of pain within
      populations. The accounts of pain sufferers are highly complex and variable.
      Multi-method studies offer an opportunity to explore these using complementary
      approaches. This may lead to both more patient-centred research and health
      service provision.

PMID- 16608583
TI  - Managing the introduction of expensive medical procedures: use of a registry.
AB  - OBJECTIVES: To explore how the adoption of medical innovations challenges tax
      financed health systems, drawing from the case of sirolimus eluting stents, a
      promising and costly innovation for percutaneous coronary interventions. METHODS:
      The coverage decisions for the new stents adopted in Emilia-Romagna, an Italian
      region, are described. The innovation was adopted through a process combining the
      development of clinical guidelines targeting their use to selected clinical
      indications, negotiation with the manufacturer for reducing price, and the
      organization of a registry for monitoring its patterns of utilization and
      assessing its effectiveness. RESULTS: Overall, 17% of the 6276 patients included
      in the registry over a 12-month period had the new stent. Wide differences
      between published trials on sirolimus eluting stents and actual clinical practice
      emerged. The new stents were frequently (23%) used in combination with
      traditional bare metal stents, and for indications (acute myocardial infarction
      and multivessel coronary disease) never included in clinical experiments (25% and
      8% of the cases, respectively). Patients' outcomes were also different, the
      overall rate of major adverse cardiac events being relatively higher (12%) than
      that shown in clinical trials. CONCLUSIONS: The actions undertaken for the new
      stents allowed a timely, and at the same time targeted and monitored, adoption of
      the innovation. This experience highlights how policy decisions related to new
      medical products could benefit from the availability of clinical databases
      providing key information on how innovations are actually used and on their
      impact on clinical practice.

PMID- 16608584
TI  - Possession of health insurance in Australia--how does it affect hospital use and
      outcomes?
AB  - OBJECTIVE: To assess the effect of possession of private health insurance on
      hospital use and outcomes in Western Australia. METHOD: Hospital morbidity
      records were extracted from the Western Australian (WA) Data Linkage System for
      all 22 major diagnostic categories (MDCs) for the period 1994-99, with follow-up
      to the end of 2000. Multivariate modelling techniques were used to estimate the
      effect of possession of private health insurance on hospital admission rates,
      average and total length of stay (LOS), cumulative incidence of admission at 30
      days and one year, and case fatality at one year. RESULTS: Possession of private
      health insurance had significant effects on hospital use and outcomes, even after
      adjustments for age, sex, aboriginality, socioeconomic status, location and
      comorbidity. Non-insured patients tended to have a higher overall hospital
      admission rate but a lower admission rate for surgical episodes, and they
      generally had a longer LOS although this difference was only greater than a day
      in three MDCs. Case fatality was higher in non-insured patients, but there was no
      systematic trend with regard to readmission rates. CONCLUSIONS: The study found
      that for all MDCs, other than those where treatment was required on an emergency
      basis, patients with private health insurance had improved access to surgical
      procedures. Either non-insured patients were disadvantaged in their access to
      surgery or the higher intervention rate in privately insured patients represented
      supplier-/consumer-induced demand which may not always have been to the patient's
      advantage or both may have occurred.

PMID- 16608585
TI  - Does size matter? The relationship between volume and outcome in the care of
      major trauma.
AB  - OBJECTIVES: To investigate the relationship between case volume and outcome for
      major trauma patients. METHODS: Prospective follow-up study of all major trauma
      patients (with injury severity score >15) arriving alive, with no invariably
      fatal injury, at 14 English emergency departments between 1990 and 1993. Using
      the stratified W statistic, an age and severity adjusted measure of outcome, the
      relationship between volume of cases and outcome was initially examined using the
      Spearman correlation coefficient. Multiple regression analysis was used to
      explore further the relationship, after adjustment for hospital-level
      characteristics. RESULTS: The smallest department saw five major trauma cases
      each year, the largest saw 96. The results of the initial correlation analyses
      indicated that there was little evidence that outcome improved with increasing
      volumes for all major trauma (rho(s) = 0.12, 95% confidence interval [CI]: -0.36
      to 0.55) nor for the cases presenting out-of-hours (rho(s) = 0.30, 95% CI: -0.19
      to 0.67). However, there was evidence that patients with multiple injury (rho(s)
      = 0.65, 95% CI: 0.27 to 0.86) and those with severe head injuries (rho(s) = 0.52,
      95% CI: 0.08 to 0.79) did better in high volume departments. This pattern, of a
      positive relationship for more complex cases was also in evidence from the
      results of the multiple regression analyses and, in particular, for patients with
      multiple injuries, was stable over time. CONCLUSIONS: While there was little
      evidence that all patients with major trauma do better in higher volume
      departments, there was evidence that patients with complex needs, such as the
      multiple injured or those with head injuries, had better outcomes.

PMID- 16608586
TI  - General practitioners with special interests: evolution and evaluation.
AB  - General practitioners with special interests (GPSIs) have emerged in the UK as a
      government initiative aimed at improving access in specialities that
      traditionally have long waiting times for investigations and treatment. This
      represents, to some extent, a formalisation of existing working practices of
      general practitioners who had obtained specialist experience during hospital
      training. GPSIs are working in a wide range of clinical areas including coronary
      heart disease, drug abuse, echocardiography and sexual health. Similar changes at
      the primary-secondary care interface are taking place in other European health
      systems. Key issues in the development of these services include the assurance of
      high-quality health care, clinical governance and risk management, cost
      effectiveness and impact on outpatient care, and the work and role of
      specialists. It is possible that these new opportunities for general
      practitioners and other health care professions will aid recruitment and
      retention of staff in primary care, enhance education and encourage commissioners
      of services to look carefully at unmet needs in their health economies. Further
      challenges include the need to train a cadre of practitioners and to provide the
      research evidence on which to base continued investment in this promising
      initiative.

PMID- 16608587
TI  - Paediatric home care: a systematic review of randomized trials on costs and
      effectiveness.
AB  - OBJECTIVE: To review systematically randomized trials (RCTs) on the effectiveness
      and costs of paediatric home care. METHODS: National Health Service (NHS) Centre
      for Reviews and Dissemination guidelines were followed. In all, 20 electronic and
      other sources were searched, using specially designed strategies. Economic
      studies and other selected designs were included, but only RCT findings--on
      service use, clinical outcomes, costs, and impact on the family--are reported
      here. Analysis is descriptive, with pooled standard mean differences used where
      meta-analysis was possible. RESULTS: About 1730 identified records up to August
      2001 were potentially relevant. In all, 10 RCTs (24 papers) were finally
      included, covering five types of paediatric home care--for very low birth weight
      or medically 'fragile' infants, for asthma or diabetes, for technology-dependent
      children, for mental health, and generic home care. Paediatric home care may
      enhance physical and mental development for very low birth weight infants and may
      be cheaper but the evidence is not strong. Home care for diabetes or asthma may
      reduce parents' costs with some clinical but no social differences noticeable. No
      randomized trials for technologically dependent children were found. Home care
      for mental health may increase parental satisfaction with services and reduce
      some health service and residential care costs. Generic home care showed no
      clinical effects at early follow-up. Partial follow-up after five years suggested
      improved psychological adjustment. No cost data were available for this care
      model. CONCLUSIONS: Despite recent expansion, research evidence from randomized
      trials for paediatric home care is slight, and methods used are weak in places.
      Paediatric home care poses practical and ethical questions that cannot be
      addressed by RCTs.

PMID- 16608588
TI  - The give and take in hospitals.

PMID- 16608589
TI  - Four days in a strange place...
AB  - NHS research governance makes it almost impossible to collect certain kinds of
      data on the everyday life of hospitals and the experience of patients.
      Fortunately, those of us who get sick enough to be admitted can write about the
      experience without fear of regulation. This paper presents some observations on
      clinical ethics, ward organization and infection control that would have been
      difficult to obtain in any other way, but which illustrate the policy and
      information costs of the present system. While not personally recommending this
      as a research strategy, the paper identifies a growing evidence gap and comments
      on its implications for the delivery of humane and well-organized care.

PMID- 16608591
TI  - What are the advantages and limitations of different quality and safety tools for
      health care?

PMID- 16608593
TI  - New Dental School in SW England: a step in the right direction.

PMID- 16608594
TI  - The role of the seven key skills portfolios in the assessment of new dental
      graduates in general dental practice.
AB  - In this article, the authors examine the role of the seven key skills portfolios
      in the assessment of new dental graduates in general dental practice. They
      discuss the nature and construction of portfolios and explore how the use of
      portfolios encourages learning. They outline what educational support is
      available and consider where key skills fit within a career pathway.

PMID- 16608596
TI  - Comparison of ultrasonic cleaning schemes: a pilot study.
AB  - OBJECTIVE: Ultrasonic cleaning is an effective method for cleaning dental
      instruments prior to sterilisation. However, there are few studies that directly
      compare precleaning and ultrasonic cleaning solutions. This study evaluated the
      efficacy of different ultrasonic cleaning schemes. METHOD AND MATERIALS: Twenty
      representative dental instruments, five of which were soiled with a mixture of
      blood and hydroxyapatite, were used in a series of cleaning runs. Cleaning
      employed a presoaking agent, ultrasonic cleaning, or a combination of both. Two
      presoaking agents (Non-ionic Ultrasonic Cleaning Solution and ProEZ Foaming
      Enzymatic Spray) plus five ultrasonic cleaners (UltraDose, General Purpose
      Cleaner, Co-enzyme Concentrate, Enzol Enzymatic Detergent, and Non-ionic
      Ultrasonic Cleaning Solution) were compared, with tap water serving as a control.
      There were two cleaning times: seven and 15 minutes. After rinsing, the working
      ends of the instruments underwent scrubbing for 20 seconds using a dental
      polishing brush held in a haemostat. After scrubbing, the brush and instrument
      were placed in a tube containing sterile saline. Vortexing of the tube lasted 30
      seconds. Testing for the post-cleaning presence of blood involved Hemastix
      dipsticks. These sticks measure minute amounts of blood in urine and can detect
      as few as 35 red blood cells per ml. Comparisons of colour change were made to a
      standard scale followed by assignment of numeric values. RESULTS: Tap water was
      the poorest cleaning solution, while UltraDose was the most effective. Blood
      removal improved when cleaning time was increased from seven to 15 minutes. The
      combined effect of a presoak immersion followed by ultrasonic cleaning was the
      most effective cleaning scheme overall. Cleaning by either ultrasound or
      presoaking only was less effective. Some instruments were more difficult to clean
      than others. CONCLUSION: Within the constraints of the small number of test runs
      performed, it was concluded that application of a presoak agent before ultrasonic
      cleaning produced the most effective instrument-cleaning regimen.

PMID- 16608597
TI  - Vocational training: a new beginning or the beginning of the end?

PMID- 16608598
TI  - Pharmaceutical prescribing for children. Part 4. Antifungal and antiviral
      therapy.
AB  - This is the fourth paper in a series on the prescribing of medicines for children
      by dentists working in primary dental care. It deals with the prescription of
      antifungals and antivirals for children.

PMID- 16608600
TI  - Quality of written reports provided by consultants in restorative dentistry to
      referring general dental practitioners in the west midlands.
AB  - OBJECTIVES: The primary objective of this study was to assess the views of
      general dental practitioners (GDPs) on the content, style, and readability of
      written reports provided by restorative consultants at a dental hospital in
      response to referral letters from the GDPs. The secondary objective was to
      determine the style of the written consultant report preferred by GDPs. SETTING:
      Referral letters received and replied to by four consultants in the restorative
      department at Birmingham Dental Hospital. METHOD: The quality of written reports
      sent by the four consultants to 100 referring GDPs in the West Midlands area was
      evaluated using a postal questionnaire, which assessed 100 GDPs' satisfaction
      with the content, style, and readability of the reports. To assess which format
      they favoured a second questionnaire was subsequently sent to the same GDPs with
      three versions of the original report in: (a) a standard format, (b) a summary
      format, and (c) a bullet point format. RESULTS: The results of the initial
      questionnaire revealed that 79 (96%) of practitioners were satisfied with the
      existing style of the reports. Following a second questionnaire in which GDPs
      were asked to choose which format they preferred, 61 (81%) expressed a preference
      for a bullet point or summary style report. CONCLUSION: The GDPs who responded to
      the questionnaires felt that a bullet point format or summary style report from
      the consultants concerned would summarise cases more clearly and concisely than
      the conventional standard format letters which they had previously received.
      Opportunities may exist for improving the quality of consultant reply letters
      through the use of structured templates and/or a summary or bullet point format.

PMID- 16608602
TI  - Future opportunities for research in primary dental care: developing research to
      support the commissioning of care.
AB  - On 23rd November 2005, there was a first for the Faculty of General Dental
      Practice (UK) [FGDP(UK)] when it hosted an open, national research study day,
      funded by the Department of Health. The study day followed on from a national
      Research and Development in Primary Dental Care meeting, 'Reflection and Moving
      Forward', held in Manchester in March 2004.

PMID- 16608603
TI  - Supplemental mandibular permanent incisor teeth: report of two cases.
AB  - Two cases of supplemental mandibular permanent incisors are presented. These
      supernumerary teeth often erupt into the dental arches causing crowding and
      aesthetic problems. Management may range from simple extraction of the
      supernumerary teeth to comprehensive orthodontic treatment. Early diagnosis may
      provide better opportunity for optimal treatment outcome.

PMID- 16608606
TI  - The obesity epidemic.

PMID- 16608607
TI  - Effect of laparoscopic versus open gastric bypass surgery on postoperative pain
      and bowel function.
AB  - BACKGROUND: This study was designed to assess postoperative pain and bowel
      function in morbidly obese patients undergoing Roux-en-Y gastric bypass (RYGBP)
      performed either by open or laparoscopic technique. METHODS: We prospectively
      studied patients scheduled for RYGBP between July 2002 and June 2003. Patients
      were assigned to the laparoscopic or open procedure by one surgeon. All patients
      received patient controlled analgesia (PCA) with intravenous morphine and rectal
      naproxen 500 mg every 12 hours. Postoperative analgesia was assessed daily using
      a visual analog scale (VAS) at rest, on walking and coughing. The amount of
      morphine used during the first 48 hours, the time of return of gastrointestinal
      motility and the time until first oral food intake were recorded. RESULTS: 53
      patients were enrolled and studied (laparoscopic group n=33, open group n=20).
      Patients undergoing laparoscopic RYGBP requested less morphine (P=0.0001) and
      showed lower VAS pain scores than patients undergoing open RYGBP. The return of
      bowel movement in the laparoscopic group occurred 1 day earlier than in the open
      group (P=0.01). The time to first passage of gas (P=0.01) and oral food intake
      (P=0.06) was shorter after laparoscopic than after open RYGBP. Patients in the
      laparoscopic group were discharged 1(1/2) days earlier than patients in the open
      group (P=0.01). CONCLUSION: The laparoscopic RYGBP operation was associated with
      less postoperative pain and morphine consumption than the open RYGBP, thereby
      facilitating an earlier recovery of intestinal motility.

PMID- 16608608
TI  - Orogastric tube complications in laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Recent national efforts have focused on improving patient safety in
      surgical procedures including examining adverse events. An adverse event in
      laparoscopic Roux-en-Y gastric bypass (LRYGBP) which has not received much
      scrutiny involves orogastric tube complications during gastric pouch formation.
      METHODS: Retrospective review was conducted of all LRYGBPs (n=727) performed by 5
      surgeons over 5 years at 2 institutions. Cases with intraoperative orogastric
      tube (OGT) related complications (n=9) were identified. RESULTS: 9 patients
      (1.2%) had preventable orogastric tube-related complications. Mean patient
      demographics were as follows: age 47 years, female 56%, pre-op BMI 52 kg/m(2), co
      morbidities 3.5 and mortality 0%. 7 of 9 patients' cases were complicated by
      stapling of an orogastric tube during gastric pouch formation. The remaining 2
      patients had complications involving suturing of the Levacuator tube during
      gastrojejunostomy formation. All complications required gastric pouch or
      anastomotic revision. 2 patients required conversion to an open procedure, 2
      required re-operation for anastomotic leak, and 1 had respiratory failure and
      prolonged hospital stay. CONCLUSION: Orogastric tube complications can occur
      during laparoscopic RYGBP, but are seldom reported and can be associated with
      significant morbidity. Treatment options are dependent upon the situation. More
      importantly, prevention strategies must include constant communication with the
      anesthesiologist and removal or manipulation of an OGT prior to stapling or
      suturing, use of large bore OGTs for increased visual or tactile recognition,
      retraction of the OGT proximal to the anastomosis during gastrojejunal
      construction and employing alternatives to esophageal temperature probes (i.e.
      Foley temperature probes).

PMID- 16608609
TI  - Zinc nutritional status of morbidly obese patients before and after Roux-en-Y
      gastric bypass: a preliminary report.
AB  - BACKGROUND: Previous researchers have found that the nutritional zinc status in
      obese and diabetic subjects is altered: low zinc concentrations in plasma and
      erythrocytes with high urinary zinc excretion were observed. This study assessed
      the influence of the Roux-en-Y gastric bypass (RYGBP) on the plasma, erythrocyte
      and urinary zinc concentrations before the beginning of the mineral
      supplementation. METHODS: 24 morbidly obese patients were studied before and 2
      months after RYGBP (the period in which the patients were still not ingesting
      mineral supplements). Fast blood sample, 24-hour urine, and 3-day food records
      were collected in the pre- and postoperative phases. Zinc concentration in the
      samples was analyzed by flame atomic absorption spectrophotometry, and dietary
      analysis of the food records were performed using the software Virtual Nutri with
      the inclusion of zinc concentration in the database for regional foods. RESULTS:
      Pre- and postoperative results were respectively: plasma 68.0 and 66.3 microg/dL;
      erythrocytes 36.6 and 43.8 microg/g Hb; urine 884.7 microg/24h and 385.9
      microg/24h; and zinc intake 10.5 and 6.7 mg/day. CONCLUSION: These results
      suggest that RYGBP changed mainly the zinc erythrocyte and urinary
      concentrations. As expected, the zinc intake was lower in the postoperative
      phase, which in the medium and long term, could cause problems for the patients.

PMID- 16608610
TI  - Relation of childhood sexual abuse and other forms of maltreatment to 12-month
      postoperative outcomes in extremely obese gastric bypass patients.
AB  - BACKGROUND: The prognostic significance of sexual abuse for extremely obese
      patients who undergo bariatric surgery is uncertain. This study examined self
      reported childhood sexual abuse and other forms of childhood maltreatment in
      relation to preoperative presentation and to 12-month postoperative outcomes in
      gastric bypass patients. METHODS: 137 extremely obese patients undergoing gastric
      bypass surgery completed a questionnaire battery before surgery and again 12
      months after surgery. Weight loss was determined with measured weight and height,
      childhood maltreatment was assessed with the Childhood Trauma Questionnaire, and
      associated eating disorder and psychological functioning were assessed with
      established measures. RESULTS: 32% of patients self-reported childhood sexual
      abuse, 37% reported some form of non-sexual childhood abuse or neglect, and 31%
      reported no form of childhood maltreatment. Significant and clinically robust
      improvements in weight and in all measures of eating and psychological
      functioning were observed at 12 months after surgery. Patients who reported
      histories of childhood sexual abuse and other forms of childhood maltreatment
      differed little from patients who reported no childhood maltreatment in body mass
      index, eating disorder features, and psychological functioning both pre- and
      postoperatively at 12-month follow-up. Patients who reported childhood sexual
      abuse had statistically significantly higher levels of depression at 12 months
      after surgery, although the depression levels represented significant reductions
      from pre-surgery and fell within the non-depressed range. CONCLUSION: Extremely
      obese patients who seek gastric bypass surgery report higher rates of childhood
      maltreatment than normative community samples. A history of childhood
      maltreatment, including reports of sexual abuse, does not appear to be a negative
      prognostic indicator for gastric bypass surgery.

PMID- 16608611
TI  - Results of laparoscopic gastric bypass in patients > or =55 years old.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is a commonly
      performed surgical intervention for morbid obesity. Some authors considered age >
      or =55 years as a relative contraindication to bariatric surgery. We examined the
      operative outcomes, weight loss, hospital stay and resolution of co-morbidities
      in patients > or =55 years old compared with those <55 years old undergoing
      LRYGBP. METHODS: From Jan 2000 to Feb 2005, 350 LRYGBPs were performed. 48
      patients > or =55 years old (13.7%) were compared to the remaining patients.
      RESULTS: Analysis of the 48 patients > or =55 years old compared with 302
      patients <55 revealed no difference in complication rate, although the older
      patients had a significantly greater percentage of serious complications. Younger
      patients lost more weight than older patients. Both groups demonstrated
      resolution of comorbidities, although the difference was not significant.
      CONCLUSIONS: LRYGBP is safe and well tolerated in morbidly obese patients > or
      =55 years. The older patients had more serious complications and lost less
      weight; however, their weight loss and resolution of co-morbidities improved
      their quality of life. Age should not be a contraindication to bariatric surgery.

PMID- 16608612
TI  - Does laparoscopic gastric bypass result in a healthier body composition? An
      affirmative answer.
AB  - BACKGROUND: Bariatric surgery results in sustained weight loss. While weight loss
      is the goal of bariatric surgery, fat loss and muscle conservation are germaine
      goals. This study investigated the hypothesis that body composition would
      significantly change after laparoscopic Roux-en-Y gastric bypass (LRYGBP).
      METHODS: Patients undergoing LRYGBP were studied. Percent fat and percent water
      were calculated via bioelectrical impedance analysis (BIA). Waist and hip
      circumference were measured in all patients as well. Measurements were taken
      preoperatively, and at 1 month, 3 months, 6 months, and 1 year. Non-parametric
      ANOVA was utilized for statistical analysis. RESULTS: There were 151 patients
      included in this study. Fat percentage (48.6 +/- 10.0 vs 34.6 +/- 10.8; P<0.001),
      total fat mass (141 +/- 37 vs 67 +/- 30; P<0.0001) and total water mass (108 +/-
      27 vs 93 +/- 23; P<0.0001) decreased postoperatively at 1 year. Water percentage
      increased postoperatively at 1 year (37.0 +/- 6.6 vs 52.5 +/- 3.3; P<0.001).
      Waist:hip ratio improved from preoperatively to 1 year postoperatively (0.895 +/-
      0.115 vs 0.811 +/- 0.076; P<0.001). CONCLUSIONS: Bariatric surgery results not
      only in fat loss but also in a change in body composition. Improved waist:hip
      ratio, fat percentage decreases, and water percentage increases all indicate an
      overall healthy body composition. While weight loss is important, improvement in
      body composition should be another recognized benefit of bariatric surgery.

PMID- 16608613
TI  - Body composition and metabolic changes following bariatric surgery: effects on
      fat mass, lean mass and basal metabolic rate.
AB  - BACKGROUND: Bariatric surgery has become the method of choice for weight loss in
      severely obese patients. While the incidence of obesity and its co-morbidities
      have been well-documented, less is known about the outcomes of the surgery as it
      relates to body composition and metabolic changes. METHODS: 19 bariatric surgery
      patients (14 female, 5 male) were assessed for basal metabolic rate (BMR),
      percent fat, fat mass, and lean body mass (LBM) just prior to surgery and at 1, 3
      and 6 months after surgery. RESULTS: Analysis of Variance (ANOVA) using the
      general linear model indicated significant changes in all measures of body
      composition for each time period. Linear regression was developed for each of
      these measures. Of the 39.7-kg weight loss, 26.4 kg (66.5%) was fat mass loss and
      13.3 kg (33.5%) was LBM loss. BMR significantly decreased from pre-surgery (2091
      kcals) to 1 month post-surgery (1758 kcals), with no significant changes in
      subsequent time periods. Repeated measures ANOVA for the ratio of BMR/LBM
      indicated no significant differences for any comparison of time periods (F=2.29,
      P=.111), suggesting that there is no adaptation of an energy-conserving mechanism
      in these patients. CONCLUSION: Bariatric surgery was highly successful in
      inducing significant changes in body weight (39.7 kg), fat mass (26.4 kg), % body
      fat (7.9%) but also lean body mass (13.3 kg). The 440 kcal decrease in BMR, while
      significant, was not greater than expected due to significant decreases in LBM.

PMID- 16608614
TI  - Is Roux-en-Y gastric bypass adequate in the super-obese?
AB  - BACKGROUND: The outcome after Roux-en-Y gastric bypass (RYGBP) in morbidly obese
      (MO) (body mass index [BMI] 40-50) was compared with super-obese (SO) (BMI >50)
      and super-super-obese (SSO) (BMI >60) patients. METHODS: A prospective study was
      conducted in 738 consecutive patients who underwent RYGBP. 483 MO were compared
      with 184 SO and 70 SSO. Study endpoints included: effect on co-morbid conditions,
      postoperative morbidity and mortality, and long-term results. Statistical
      analysis utilized SPSS 11.0. RESULTS: Percentage of males was significantly
      greater in the SO groups (16.5% vs 13%, P=0.01). Obesity-related conditions were
      significantly more frequent in the SO groups: sleep apnea (38% vs 17%, P<0.0005),
      gallstones (23% vs 14%, P=0.013); diabetes (29% vs 17%, P=0.002). Hospital stay
      was longer in the SO groups (5.7+/-6.1 days vs 4.6+/-2.6 days, P=0.024). Wound
      infection was more frequent in the SO groups (4.7% vs 1.4%, P=0.019).
      Postoperative mortality was greater in the SSO and SO groups (1.6% and 1.4%) than
      MO (0%) (P=0.019). Incisional hernia was more frequent in the SO groups (14.1% vs
      8.6%; P=0.041). There was no significant difference in percent of excess weight
      loss (%EWL) between the three groups. EWL >50% at 5 years was: MO 81.5%, SO
      87.5%, SSO 80%. The surgery was effective in treating the co-morbid conditions.
      CONCLUSION: RYGBP achieved significant durable weight loss and effectively
      treated co-morbid conditions in SO and SSO patients with acceptable postoperative
      morbidity and slightly greater mortality than in MO patients.

PMID- 16608615
TI  - Laparoscopic gastric re-banding versus laparoscopic gastric bypass as a rescue
      operation for patients with pouch dilatation.
AB  - BACKGROUND: The authors assessed whether laparoscopic rebanding or laparoscopic
      Roux-en-Y gastric bypass (LRYGBP) is the best approach for failed gastric banding
      after pouch dilatation. METHODS: Between January 2000 and June 2005, 489 patients
      underwent laparoscopic gastric banding, and of these, 33 (6.7%) required rescue
      procedures for pouch dilatation. Each reoperated patient was contacted to obtain
      information about their postoperative course. Additionally, preoperative weight
      and BMI, weight loss at 1 year postoperatively, weight at time of pouch
      dilatation and the time-period between the primary operation and pouch dilatation
      were analyzed. RESULTS: The most common operation for pouch dilatation was band
      repositioning or rebanding (16 patients). Band removal without replacement was
      performed in 7 patients. 8 patients underwent conversion to a LRYGBP. 1 patient
      underwent laparoscopic gastric sleeve resection and 1 patient received an
      intragastric balloon. Patients who underwent conversion to LRYGBP are very
      content and, although weight loss has been nearly the same as after gastric
      banding, they would prefer the gastric bypass operation to the gastric banding.
      CONCLUSION: Conversion to LRYGBP appears to offer significant advantages, and
      appears to be the rescue therapy of choice after failed laparoscopic gastric
      banding.

PMID- 16608616
TI  - Roux-en-Y gastric bypass versus a variant of biliopancreatic diversion in a non
      superobese population: prospective comparison of the efficacy and the incidence
      of metabolic deficiencies.
AB  - BACKGROUND: In the non-superobese population, an agreement has not been made as
      to the optimal bariatric operation. The present study reports the results of a
      prospective comparison of Roux-en-Y gastric bypass (RYGBP) and a variant of
      biliopancreatic diversion (BPD) in a non-superobese population. METHODS: From a
      cohort of 130 patients with BMI 35 to 50 kg/m(2), 65 patients were randomly
      selected to undergo RYGBP and 65 to undergo BPD. All patients underwent complete
      follow-up evaluation at 1, 3, 6, and 12 months postoperatively and every year
      thereafter. RESULTS: Patients in both groups have completed their second
      postoperative year. Mean % excess weight loss (%EWL) was significantly better
      after BPD at all time periods (12 months, P=0.0001 and 24 months, P=0.0003), and
      the %EWL was >50% in all BPD patients compared to 88.7% in the RYGBP patients at
      2-year follow-up. No statistically significant differences were observed between
      the 2 groups in early and late non-metabolic complications. Hypoalbuminemia
      occurred in only 1 patient (1.5%) after RYGBP and in 6 patients after BPD (9.2%).
      Only 1 patient from each group was hospitalized and received total parenteral
      nutrition. Glucose intolerance, hypercholesterolemia, hypertriglyceridemia and
      sleep apnea completely resolved in all patients in both groups, although mean
      total cholesterol level was significantly lower in BPD patients at the second
      year follow-up (t-test, P<0.0001). Diabetes completely resolved in all BPD
      patients and in 7 of the 10 diabetic RYGBP patients. CONCLUSION: Both RYGBP and
      BPD were safe and effective procedures when offered to non-superobese patients.
      Weight loss after BPD was consistently better than that after RYGBP, as was the
      resolution of diabetes and hypercholesterolemia. Because the nutritional
      deficiencies that occurred following this type of BPD were not severe and were
      not significantly different between the 2 operations, both may be offered to non
      superobese patients, keeping in mind the severity and type of preoperative co
      morbidities as well as the desired weight loss.

PMID- 16608617
TI  - Understanding patients' value of weight loss and expectations for bariatric
      surgery.
AB  - BACKGROUND: Few studies examine patients' expectations for bariatric surgery or
      the value patients place on weight loss. METHODS: 44 patients planning to undergo
      bariatric surgery were surveyed to examine patients' expectations and motivations
      for surgery. We also quantified how much patients valued different health and
      weight loss states using the standard gamble, an approach that estimates an
      outcome's value based on a patient's willingness to risk death to achieve the
      outcome. Utilities ranging from 0 to 1.00 were calculated where 1.00 represented
      the most desired state. RESULTS: Mean age of the patients was 42.6 years, and
      mean body mass index was 47.1 kg/m(2). The majority were women (n=42) and white
      (n=29), and reported poor quality of life. Most patients considered surgery for
      health reasons. Patients expected to lose 38% of their total body weight and
      would be disappointed if they did not lose at least 24% of their body weight.
      Significantly more patients were willing to risk death to achieve their "dream"
      weight (n=40) than to lose 20% (n=32) or 10% (n=17) of their total body weight.
      The respective utilities for these weight states were 0.98, 0.94, and 0.92. More
      patients were willing to risk death to undergo surgery (n=42) than to achieve a
      permanent weight loss of 20% (n=32), P<0.004. CONCLUSION: Patients appeared to
      value weight loss highly but had unrealistic expectations for bariatric surgery.
      Future studies should examine whether patient expectations, motivations, and
      value for realistic weight losses might predict outcomes and satisfaction after
      surgery.

PMID- 16608618
TI  - Metabolic profile in severely obese women is less deteriorated than expected when
      compared to moderately obese women.
AB  - BACKGROUND: Obesity is well known to be associated with an increased prevalence
      of metabolic complications. Severe obesity is thus expected to have more
      important alterations of the metabolic profile than moderate obesity. This study
      aimed to compare the metabolic profile of pre- and postmenopausal severely obese
      women with moderately obese women. METHODS: First, the metabolic profile of pre-
      (n=165) and postmenopausal (n=43) severely obese women (body mass index (BMI) >
      or =40 kg/m(2)) was compared to that of pre- (n=52) and postmenopausal (n=35)
      moderately obese women (BMI of 30-40 kg/m(2)). Thereafter, pre- and
      postmenopausal severely obese women were divided into two subgroups according to
      the presence/absence of a dysmetabolic profile. We used for comparison, a group
      of pre- and postmenopausal moderately obese women without a dysmetabolic profile.
      RESULTS: The metabolic profile of pre- and postmenopausal severely obese women
      was less deteriorated than expected when compared to moderately obese women.
      Moreover, severely obese women with or without a dysmetabolic profile displayed
      comparable or even lower plasma levels of cholesterol, HDL and LDL-cholesterol,
      and a lower cholesterol/HDL-cholesterol ratio than moderately obese women (P< or
      =0.05). After menopause, the metabolic profile of severely obese women,
      dysmetabolic or not, was similar to that of moderately obese women. Blood
      pressure was, however, higher in severely obese women compared to moderately
      obese women, only before menopause (P< or =0.0001). CONCLUSION: These results
      indicate that despite their large accumulation of adipose tissue, most of the
      severely obese women had a metabolic profile less deteriorated than expected,
      when compared to moderately obese women.

PMID- 16608619
TI  - Pre-pyloric neural electrical stimulation produces cholinergically-mediated
      reverse peristalsis in the acute canine model of microprocessor-invoked gastric
      motility for the treatment of obesity.
AB  - BACKGROUND: Gastric Electrical Stimulation (GES) has been suggested as a new tool
      for the treatment of obesity. Among the known methods for GES, only Neural
      Gastric Electrical Stimulation (NGES) provides direct control of contractility
      without utilizing the spontaneously existing gastric electrical activity as an
      intermediary. However, only one of the established GES techniques, gastric
      pacing, has been described to produce retrograde peristalsis for delaying gastric
      emptying. The aim of this study was to explore the possibility of producing
      retrograde peristalsis using either single electrode set or dual electrode set
      NGES. METHODS: 8 anesthetized dogs underwent laparotomy and implantation of 2
      circumferential electrode sets approximately 3 cm and 7 cm proximal to the
      pylorus, respectively. Single-set and dual-set NGES sessions were repeatedly
      administered using a custom-designed implantable neurostimulator. Gastric
      motility patterns were captured using 3 force transducers implanted on the
      anterior gastric wall along the gastric axis. Motility indices and velocities
      were employed to quantify the produced contractile patterns. RESULTS: Both single
      set and dual-set NGES produced circumferential lumen-occluding contractions in
      the vicinity of the electrode sets. The invoked contractions propagated
      proximally in a retrograde fashion. The propagation scope was different depending
      on the number of electrode sets used. Different velocities of the invoked
      retrograde contractions associated with single- and dual-set NGES were observed
      and quantified. Contractility patterns reflected by the normalized motility
      indices were very similar regardless of the electrode stimulation technique.
      CONCLUSION: Pre-pyloric NGES can produce controlled retrograde peristalsis and
      serve as another avenue for the treatment of obesity.

PMID- 16608620
TI  - Revision of failed gastric banding to mini-gastric bypass.
AB  - BACKGROUND: Although laparoscopic adjustable gastric banding (LAGB) has been
      found to be a generally successful weight loss operation, there are reports of
      occasional LAGB failure. The results of rescue procedures for these patients are
      important. The mini-gastric bypass (MGB) is a safe and effective alternative to
      other bariatric surgical procedures. We report the results of conversion of 3
      failed LAGB procedures to MGB. METHODS: In a series of 2,595 patients who
      underwent MGB, 3 had previously undergone an LAGB that failed to sustain weight
      loss. RESULTS: Average operative time was 54 minutes in LAGB conversions to MGB
      (compared to 37.5 minutes in primary MGB), and length of stay was 1 day. There
      were no complications in the patients converted MGB. The weight loss in converted
      MGB patients was similar to the weight loss in primary MGB patients, with a mean
      weight loss at 1 year of 60 kg (79% of excess weight) CONCLUSION: Conversion of
      failed LAGB to MGB was a safe procedure that added approximately 20 minutes to
      the short MGB operating time. Patient satisfaction was high, recovery was rapid,
      and weight loss was very good.

PMID- 16608621
TI  - Mucocele of the gastric tube after conversion of vertical banded gastroplasty to
      duodenal switch: not just a radiological image.
AB  - We present two patients who underwent a duodenal switch operation after a failed
      vertical banded gastroplasty. Both patients had a complicated postoperative
      course because of an abdominal infection, and both presented the radiological
      image of a gastric fundus mucocele in the part of the fundus excluded between two
      staple-lines. Although initially considered as a radiological image with no
      clinical significance, the presentation of the second case with the same
      abdominal complication led us to contemplate the possibility of a connection
      between the gastric mucocele and the postoperative infection.

PMID- 16608622
TI  - Mucocele of the gastric tube after conversion of VBG to DS.

PMID- 16608624
TI  - Is routine preoperative upper endoscopy in gastric banding really necessary?

PMID- 16608625
TI  - [Trends in science].

PMID- 16608626
TI  - Tumor-induced hypophosphatemic osteomalacia associated with tertiary
      hyperparathyroidism: a case report.
AB  - BACKGROUND: Tumor-induced hypophosphatemic osteomalacia is a syndrome
      characterized by urinary phosphate wasting related to the presence of a slowly
      growing tumor of mesenchymal origin. The characteristic laboratory findings are
      normal serum calcium, marked hypophosphatemia, increased serum alkaline
      phosphatase, markedly reduced renal tubular reabsorption of phosphorus and
      inappropriately low levels of 1,25-dihydroxyvitamin D [1,25-(OH)2D]. CASE
      PRESENTATION: A 65-year-old woman presented with a 17-year clinical history of
      musculoskeletal pain, muscular weakness in the pelvic girdle, spontaneous
      fractures and difficulty in walking. Over the ensuing years the patient suffered
      other multiple spontaneous fractures, surgically treated, and the muscular pains
      worsened until she became bedridden. During the years before hospital admission
      the patient received treatment with clodronate, oral calcium salts and vitamin D
      therapy. Standard laboratory, ultrasonography and scintigraphic findings provided
      a "convenient" diagnosis of primary hyperparathyroidism, but the low plasma level
      of phosphorus induced to perform an Indium111-octreotide scintigraphy.
      Scintigraphy visualized an area of pathologic increased signal uptake in the left
      groin, consistent with a mass containing a high density of somatostatin
      receptors. After surgery, histologic examination and immunostaining of the
      resected specimen indicated an hemangiopericytoma. Nevertheless, the persistently
      low blood phosphorus level, in association with the increased serum calcium and
      PTH levels, were attributed to the prolonged phosphate therapy the patient
      underwent over the years, and the persisting abnormal laboratory indexes
      indicated the development of a tertiary hyperparathyroidism. We performed a
      subtotal parathyroidectomy and intraoperative assay of serum PTH showed that
      levels had diminished by more than 80% from preoperative values. Over the ensuing
      months Ca+2, PTH and serum phosphorus values returned to normal, and the pain
      symptoms disappeared. CONCLUSIONS: Tumour-induced osteomalacia is a very rare
      syndrome associated in 5% of cases with tertiary hyperparathyroidism due to long
      term therapy with phosphorus and vitamin D. The initial diagnosis of primary
      hyperparathyroidism, confirmed by the parathyroid MIBI-scintigraphy, would lead
      us to an inappropriate surgical treatment. Therefore we want to stress the
      importance of In111-octreotide scintigraphy in detecting tumours, rich in
      somatostatin receptors, in presence of an hypophosphatemic syndrome.

PMID- 16608627
TI  - [Complicated diverticular disease. Three cases of colovesical fistulas and review
      of literature].
AB  - Colovesical fistulas represent a possible less frequent complication of
      diverticular disease of colon. They represent a complex condition because of the
      possible and unexpected evolution into a septic shock with a high risk of death.
      The Authors report three cases of colovesical fistula as a complication of
      diverticular disease. They underline the importance of early diagnosis, specific
      antibiotic therapy and appropriate surgical therapy realized in one or two stages
      according to general and local conditions of each patient.

PMID- 16608628
TI  - [Surgical treatment of Crohn's disease complications. Our experience].
AB  - Thirty-five patients with Crohn's Disease (CD) were observed: 18 have been
      treated with medical therapy and 17 (48.6%) underwent to surgical treatment : 1)
      intolerance to the medical treatment in 5.9% (1 case); 2) local complications in
      94.1% (16 cases: 6 stenosis, 2 occlusions, 3 abscesses, 3 fistulas, 1 perforation
      with peritonitis, 1 case toxic megacolon). The operations have been 19: resective
      interventions 14 (bowel and/or colon resections), conservative interventions 5.
      The mortality was 0, the morbidity 35,29%. The incidence of the recurrences in a
      follow up of 5 year was 42,9%. The Authors conclude that the surgery, indicated
      for the treatment of complications, can be resective surgery (perforating Crohn
      disease: fistulas, abscess) or conservative surgery (stenosing Crohn disease:
      stenosis). Recently the conservative intervention are proposed in the treatment
      of fistulas and abscesses too, but when the inflammation is mild and in patients
      that underwent to extensive intestinal resection with risk of short bowel
      syndrome.

PMID- 16608629
TI  - Traumatic avulsion of the intrapancreatic common bile duct: case report.
AB  - Injuries of the extra hepatic biliary tree following blunt trauma to the abdomen
      are rare. We present a case of avulsion of the intrapancreatic common bile duct.
      Very often the lesion is not identifiable until the signs of jaundice and biliary
      ascites occur. Intraoperative cholangiography is mandatory for the diagnosis, but
      the noninvasive magnetic resonance cholangiopancreatography could readily depict
      the injury of the extrahepatic bile duct preoperatively. When the diagnosis is
      late the corner stone of treatment is biliary diversion and definitive repair
      after complete resolution of sepsis with a choledochojejunostomy.

PMID- 16608630
TI  - [A case of amputation neuroma of the bile duct following video-laparoscopic
      cholecystectomy].
AB  - We report a case of neuroma of the common hepatic duct arising five years after
      cholecystectomy (laparoscopic then converted in laparotomy). A 73-years-old
      patient was admitted for obstructive jaundice. Ultrasonography, TC and
      cholangiography showed a nodular lesion of the common hepatic of 1 cm in
      diameter, causing a regular and important stenosis of the main bile duct.
      Histologic examination demonstrated neuroma. By the analysis of this and 42 other
      previously published cases, the following features of bile duct neuroma were
      outlined: 1) variable interval between cholecystectomy and the onset of jaundice
      (2 months to 40 years); 2) the same incidence after laparoscopic or laparotomic
      cholecystectomy; 3) the generally complicated postoperative course after first
      surgical approach; 4) the various localizations on the biliary tree (cystic, main
      bile duct, intrahepatic ducts); 5) the circumstances of onset are almost the same
      (obstructive jaundice); 6) the histologic examination is mandatory for a correct
      diagnosis; and 7) the best treatment is resection of the bile duct tract involved
      in neuroma and reconstruction of biliary tree with hepaticojejunostomy.

PMID- 16608631
TI  - [Retroperitoneal mass: a clinical case].
AB  - The Authors discuss about a case of retroperitoneal mass, recently observed in
      their Institution. About the nature of the mass, by the imaging and clinical
      evolution, the Authors suppose a traumatic genesis: subcapsular renal hematoma,
      occurred 2 years before, broken and expanded in retroperitoneal space and then
      superficialized in the left lumbar region.

PMID- 16608632
TI  - [Ductal carcinoma in situ of the breast].
AB  - The Authors report their experience about 127 ductal carcinoma in situ (DCIS) of
      the breast. Guidelines for surgical treatment are: radiological or clinical
      diagnosis, tumor's extension, histological classification, grading and margin
      status. At the present the Authors prefer breast conserving surgery with tumor
      margin's study. They report their experience in the last seven years about
      sentinel node biopsy. Radiotherapy and endocrine therapy are indicated for
      selected patients; local recurrence after DCIS therapy is 8,1% on a 6,1 years
      follow-up.

PMID- 16608633
TI  - [Peritoneal papillary serous carcinoma in a patient with previous surgery for
      breast cancer: clinical case].
AB  - The peritoneal papillary serous carcinoma (PPSC) is a rare tumor more frequently
      revealed in female. The onset mean age is 56 years. It implicate peritoneum,
      ovary's surface and pelvis. The histology of this disease is similar to papillary
      serous carcinoma ovary (PSCO). The PPSC histogenesis is probably correlated to
      coelomatic embryonal epithelium. Clinical characteristics are abdominal swelling,
      constipation, nausea, emesis, inappetence, feel unwell, lose weight. The
      cytoreductive surgery and the cisplatinum chemotherapy, and other treatments like
      immunotherapy and radiotherapy, increase the PSCP patient survival. A case of a
      51 years old patient with previous surgery for breast cancer is here described.
      She show some of the yet described clinical findings. At the surgery we found the
      typically serous peritoneal localizations. We performed a debulking, and the
      patient died 14 months after the operation due to the disease progression.

PMID- 16608634
TI  - [Day surgery for breast cancer in the elderly].
AB  - Early diagnosis of breast cancer and improvement of new technologies for
      identification and analysis of sentinel node allow more conservative surgical
      approaches, which guarantee both excellent local control and a good quality of
      life, also in elderly patients. We have studied a series of 28 women aged 70
      years or older and affected by breast cancer. They underwent breast-preserving
      surgery either alone or in association with axillary lymphadenectomy and all of
      them had early discharge from hospital. This approach demonstrated to be safe and
      effective, so we may conclude that day-surgery treatment of breast cancer in
      these patients is possible in the majority of cases, is associated with low
      morbidity and is profitable for clinical, social and economic issues.

PMID- 16608635
TI  - [Intragastric balloon in bariatric surgery].
AB  - Intragastric balloon (BIB) is a mechanical restrictive device formed by a
      silicone wrapper inserted endoscopically in the stomach, filled with 500 cc of
      physiological blue methyl solution and kept in situ for 6 months. In two years 98
      intragastric balloon have been set in 88 patients at the average age of 37.1
      years, of 41.9 of BMI and 47.6 kg of weight. Complications were intolerance,
      gastro-oesophageal reflux, break and/or deflation and meteorism. BIB is an
      effective procedure in the temporary treatment of obesity leading to satisfactory
      weight loss and to short-term improvement of comorbidities.

PMID- 16608636
TI  - [Inguinal hernioplasty with PHS: our experience].
AB  - Three hundred patients underwent inguinal hernia repair from January 2003 to
      December 2004; 40 patients, randomly selected, received the PHS (Prolene Hernia
      System) mesh. Surgery was performed under local anesthesia in 80% of cases and
      under spinal anesthesia in the remaining 20%. There were 29 men and 11 women;
      mean age was 58,5 years (range 39-78). Postoperative pain was light and morbidity
      was low; all patients had early return to normal activities. Particularly, there
      were differences between the self-employed and the employees: the former began
      work again 2-4 days after surgery in 85% of cases, while the latter began after
      15-20 days. Immediate complications were rare and always minor: they included
      seroma (1%) and ecchymosis (1%). Follow-up examinations did not show any
      recurrences.

PMID- 16608637
TI  - The role of popliteal artery embolectomy in the management of acute lower limb
      ischemia: our experience.
AB  - INTRODUCTION: The Authors report their experience in the management of acute
      lower limbs ischemia through distal popliteal artery approach. PATIENTS AND
      METHODS: Five popliteal embolectomy through a medial approach were performed; in
      one patient a posterior approach was carried out. Patients were included in two
      groups on the basis of ischemia duration: group A<6 hours (3 patients) and group
      B>6 hours (3 patients). Colour-duplex scan was performed in all the patients The
      arteriotomy was closed with interrupted 7/0 monofilament polypropylene sutures.
      RESULTS: There were no peri-operative deaths. The primary limb salvage rate was
      83.3% (5 patients). In one case (16.7%) a major amputation was performed. In one
      case (16.7%) a drop foot occurred. CONCLUSIONS: The popliteal embolectomy is
      followed by excellent results and should be consider prior to thrombolysis or
      bypass graft revascularization. An appropriate use of duplex scan and a medial
      approach can lead to an high successful rates in terms of limb function and limb
      salvage also in cases with delayed ischemia.

PMID- 16608639
TI  - [Increase in accuracy and meaningful content of pathological diagnosis].

PMID- 16608640
TI  - [Lobular carcinoma-in-situ and ductal hyperplasia of breast].

PMID- 16608641
TI  - [Relationship between lymph node metastasis and pathologic features of invasive
      micropapillary carcinoma of breast].
AB  - OBJECTIVE: To investigate the relationship between lymph node metastasis and
      pathologic features of invasive micropapillary carcinoma (IMPC) of the breast.
      METHODS: Histopathologic features and status of lymph node metastasis of fifty
      one cases of IMPC were studied by microscopic examination, immunohistochemical
      staining (VEGF-C and VEGFR-3) and analysis of lymphatic vessel density. RESULTS:
      (1) The number of positive lymph nodes in histologic grade II/III IMPCs was
      significantly higher (mean 12.5) than that in histologic grade I tumors (mean
      4.0). (2) The incidence of nodal metastases in IMPCs with lymphocyte infiltration
      (+)/(++) was significantly higher (27/28, 96.4%) than that in tumors with no or
      minimal lymphocyte infiltration (-)/(+/-) (14/23, 60.9%), and the number of
      positive nodes was also higher (mean 14.4) in tumors with lymphocyte infiltration
      compared with those without (mean 4.6). (3) In IMPCs with histologic grade
      II/III, the expression of VEGF-C was significantly higher than that of histologic
      grade I tumors (P = 0.03). VEGF-C expression was in positive correlation with
      lymph node metastasis (P = 0.006) and lymphatic vessel density (P = 0.009). Lymph
      node metastasis was also correlated with lymphatic vessel density (P = 0.007).
      (4) The percentage of IMPC component in the tumor did not correlate with nodal
      metastasis. The metastatic foci in lymph node were all IMPC or mainly IMPC. (5)
      Fourteen of twenty-eight cases (14/28, 50%) of IMPC containing ductal carcinoma
      in-situ (DCIS) were DCIS of micropapillary type. CONCLUSIONS: The histologic
      grade, lymphatic vessel density and lymphocyte infiltration are key histological
      features that are correlated with lymph node metastasis of IMPC. The expression
      of VEGF-C and VEGFR-3 may play an important role in the development of lymph node
      metastasis of IMPC. Micropapillary type DCIS may be the early stage of IMPC.

PMID- 16608642
TI  - [Spindle cell carcinoma of breast with neuroendocrine differentiation].
AB  - OBJECTIVE: To describe the morphologic features and immunohistochemistry of
      spindle cell carcinoma of breast with neuroendocrine differentiation. METHODS:
      Retrospective review of 2500 cases of breast carcinoma showed 5 cases (0.2%) with
      a predominance (> 80%) of spindle cell component. Amongst the 5 cases studied, 2
      represented intraductal spindle cell carcinoma and 3 represented invasive spindle
      cell carcinoma. The paraffin sections were stained with hematoxylin and eosin,
      alcian blue, periodic acid-Schiff and reticulin stain. Immunohistochemical
      studies for AE1/AE3, CEA, EMA, CK7, 34betaE12, NSE, synaptophysin, chromogranin
      A, Leu-7, vimentin, S-100, SMA, calponin, estrogen receptor, progesterone
      receptor, c-erbB2, E-cadherin, Ki-67 and p53 were also carried out. Follow-up
      information was available in 4 of the 5 cases. RESULTS: The mean age of the
      patients was 68 years. Histologically, all tumors were predominantly composed of
      elongated spindle cells. Three of these cases also contained tumor cells with
      vacuolated cytoplasm, alcian blue-positive tumor cells were observed in 4 cases.
      Immunohistochemically, the spindle tumor cells in all cases expressed AE1/AE3,
      CEA, EMA, E-cadherin and synaptophysin. CK7 was positive in 4 cases, NSE in 3
      cases, chromogranin A and Leu-7 in 2 cases. Estrogen receptor was expressed in 4
      cases and progesterone receptor in 2 cases. Overexpression of c-erbB2 oncoprotein
      was detected in only 1 case. Vimentin was focally positive in 1 case. Two cases
      of intraductal spindle cell carcinoma and 1 of the 3 cases of invasive spindle
      cell carcinoma were classified as neuroendocrine carcinoma of spindle cell type,
      while the remaining 2 cases of invasive spindle cell carcinoma were considered as
      metaplastic carcinoma with neuroendocrine differentiation. Amongst the 4 patients
      with follow-up information available, 3 were still alive 24 to 58 months after
      the initial diagnosis. One patient died within 27 months of diagnosis.
      CONCLUSIONS: The presence of spindle tumor cells and sometimes intracytoplasmic
      mucin are useful morphologic clues in diagnosing spindle cell carcinoma of the
      breast with neuroendocrine differentiation. Intraductal neuroendocrine spindle
      cell carcinoma needs to be distinguished from usual ductal hyperplasia and
      intraductal papilloma. On the other hand, invasive spindle cell carcinoma with
      neuroendocrine differentiation needs to be distinguished from spindle cell
      myoepithelioma, malignant melanoma and sometimes soft tissue neoplasm.

PMID- 16608643
TI  - [Actinomycosis of ovary: report of a case].

PMID- 16608644
TI  - [Correlation between MMP-2 activation and MT1-MMP mRNA expression in thymic
      epithelial tumors].
AB  - OBJECTIVE: To study the relationship between activation of pro-MMP-2 and
      expression of matrix metalloproteinases (MMP)-2, MT1-MMP and tissue inhibitor of
      metalloproteinases (TIMP)-2 mRNA in thymoma and thymic carcinoma; and to study
      the molecular mechanism of invasion and metastasis of thymic epithelial tumors.
      METHODS: Fresh tissue specimens of thymoma, thymic carcinoma and normal thymus
      were included. The mRNA expression of MMP-2, MT1-MMP and TIMP-2 were analyzed by
      real-time reverse transcription polymerase chain reaction. The pro-MMP-2
      activation ratio and its localization were determined by gelatin zymography and
      film in-situ gelatin-Zymography, respectively. Correlation of mRNA expression of
      MMP-2, MT1-MMP and TIMP-2 was investigated in tumors with different histological
      subtypes and clinical stages. RESULTS: There were no significant differences in
      the expressions of MMP-2, MT1-MMP and TIMP-2 mRNA between I and II stage or III
      and IV stage thymomas (P > 0.05). However, significant differences of the
      expressions were observed between three tumor groups: I-II stage, III-IV stage
      and thymic carcinomas (P < 0.005), and between three histological subtypes: AB-B1
      (lymphocyte-rich and mixed types), B2-B3 (cortical and predominantly polygonal
      cells types) and thymic carcinomas (P < 0.05). Expression levels of MT1-MMP and
      TIMP-2 mRNA were correlated with pro-MMP-2 activation ratio (Spearman rank
      correlation: r = 0.7235, r = 0.7647, P < 0.005). The expression of MMP-9 did not
      show significant differences between thymomas and thymic carcinomas. CONCLUSIONS:
      MMP-2, MT1-MMP and TIMP-2 mRNA expression levels are correlated with the
      histologic subtypes and clinical stages of thymoma. The mRNA expressions of MT1
      MMP and TIMP-2 are correlated with the activation ratio of pro-MMP-2. It is
      speculated that upregulation of MT1-MMP gene expression may induce an activation
      of pro-MMP-2 through TIMP-2.

PMID- 16608645
TI  - [Expression of PAR-1 in human lung carcinoma and its relationship with tumor
      metastatic potential].
AB  - OBJECTIVE: To explore the correlation between expression of PAR-1 and metastasis
      of human lung carcinoma. METHODS: Expression levels of PAR-1 were examined in
      surgically resected lung carcinoma specimens and corresponding lymph nodes by RT
      PCR and immunohistochemistry, combined with morphometric methodology and
      clinicopathologic profiles. RESULTS: Strong PAR-1 staining was detected in the
      periphery of carcinoma nests, adenocarcinomatous emboli, foci of atypical
      adenomatous hyperplasia adjacent to the adenocarcinoma and atypical proliferation
      of duct epithelium of bronchial mucous glands. The expression rates of PAR-1 were
      73.8% (59/80) and 63.9% (23/36) by immunohistochemistry and RT-PCR respectively.
      The percentage of PAR-1 protein expression cells was significantly higher in
      tumors with metastasis (85.7%, 48/56) than those without (45.8%, 11/24).
      Morphometric study demonstrated that there were significant differences of PAR-1
      protein expression levels between tumors with metastatic and those without,
      primary and metastatic carcinomas, primary carcinomas and benign lung tissues
      adjacent to the carcinoma. No significant correlation was found between PAR-1
      expression level and tumor size, histological types and tumor grades. The
      positive rate of PAR-1 mRNA expression in the metastatic group was significantly
      higher than that of the non-metastatic group (78.3%, 18/23 v.s. 38.5%, 5/13).
      CONCLUSION: PAR-1 expression may play an important role in determining the
      malignant phenotypes of lung cancers and significantly contribute to their
      initiation, progression and metastasis.

PMID- 16608647
TI  - [Promoter methylation and mRNA expression of APC gene in MCF10 breast cancer
      model].
AB  - OBJECTIVE: To investigate the promoter methylation status and mRNA expression of
      APC gene in MCF10 model of breast cancer progression. METHODS: Methylation
      specific PCR and sodium bisufite genomic sequencing were employed to detect the
      methylation status of APC promoter 1A in normal breast tissues, conventional
      breast cancer cell line MCF-7 and MCF10 model cell lines including MCF10A (breast
      hyperplastic cell line, non-tumorigenic), MCF10AT (pre-malignant cell lines,
      producing slowly progressing hyperplastic and dysplastic lesions), MCF10DCIS.com
      (breast ductal carcinoma in-situ cell line, producing ductal carcinoma in-situ),
      MCF10CA1a, MCF10CA1d, MCF10CA1h cell lines (invasive breast carcinoma cell line,
      forming aggressive tumors of different morphology and metastatic potential). In
      addition, mRNA expression of APC was determined by reverse transcriptase PCR and
      real-time PCR assays. RESULTS: Hypomethylation of APC promoter 1A was identified
      in hyperplastic cell line MCF10A, pre-malignant cell line MCF10AT, ductal
      carcinoma in-situ cell line MCF10DCIS.com, invasive carcinoma cell lines
      MCF10CA1a, MCF10CA1d, MCF10CA1h and normal breast tissue. MCF-7 showed partial
      methylation at the promoter. Statistically significant reduction of APC mRNA
      expression was not found in all MCF10 cell lines and MCF-7, compared with that of
      normal breast tissue (MCF10AT, MCF10CA1a, MCF10CA1d, MCF10CA1h and MCF10DCIS.com
      showed reduced mRNA expressions of APC at 0.27, 0.96, 1.78, 2.70, and 2.03 times
      respectively. MCF10A and MCF-7 even showed an increase of APC mRNA expression at
      0.02 and 0.33 times, respectively). CONCLUSION: The aberrant promoter methylation
      of APC is not related to the breast cancer progression, at least in the MCF10
      model system.

PMID- 16608646
TI  - [Mixed epithelial and stromal tumor of kidney].
AB  - OBJECTIVE: To study the clinicopathological features and differential diagnoses
      of mixed epithelial and stromal tumor of the kidney. METHODS: Clinical and
      pathological characteristics of 4 cases of mixed epithelial and stromal tumor of
      the kidney were studied. RESULTS: Three patients were female and one was male.
      All patients presented with flank pain and hematuria. Radiologic studies revealed
      cystic and solid masses involving the kidney. Grossly the tumors had a solid and
      cyst appearance. Microscopically, the tumors were composed of a mixture of
      stromal and epithelial elements. The epithelial elements were variable in cell
      types including cuboidal, hobnail and columnar cells. One case showed Mullerian
      and intestinal epithelial differentiations. Stromal elements essentially
      consisted of spindle cells, with thick-walled blood vessels and bands of smooth
      muscle cells as distinctive features of the tumor. Immunohistochemical staining
      revealed that the epithelial components were positive for AE1/AE3, whereas the
      stromal components were positive for ER, PR, and SMA. All patients underwent
      nephrectomy and were well without evidence of recurrence. CONCLUSIONS: Mixed
      epithelial and stromal tumor of the kidney is a benign neoplasm with distinct
      histopathological features. It should be distinguished from many other renal
      neoplasms. Surgical intervention is a preferred therapy.

PMID- 16608648
TI  - [Influence of beta-amyloid peptide on cell membrane lipids and cholinergic
      receptors in human neuroblastoma SH-SY5Y cells].
AB  - OBJECTIVE: To study the effects of beta-amyloid peptide (Abeta) on cell membrane
      lipids and cholinergic receptors of human neuroblastoma cells. METHODS: Human SH
      SY5Y neuroblastoma cells were treated with different concentrations of Abeta(1
      42) with and without pretreatment of vitamin E. MTT [3-(4, 5-dimethylthiazol-2
      yl)-2, 5-diphenyltetrazolium bromide] reduction, lipid peroxidation, protein
      oxidation and phospholipids were measured by spectrophotometry. Levels of
      cholesterol and unbiquinone were determined by high-performance liquid
      chromatography (HPLC). The numbers of cholinergic receptor binding sites were
      determined by receptor binding assay and the protein levels of nicotinic receptor
      alpha3 and alpha7 subunits were studied by Western blotting. RESULTS: SH-SY5Y
      cells showed decreased reduction rates of MMT and phospholipids, and increased
      lipid peroxidation and protein oxidation after exposure to Abeta (0.1 micromol/L)
      as compared to the control. The number of cholinergic receptor binding sites, the
      protein level of nicotinic receptor alpha3 and alpha7 subunits and the content of
      ubiquinone decreased in cells treated with high dose of Abeta (1 micromol/L).
      Although the level of cholesterol was not changed in any way, vitamin E partially
      prevented the neurotoxic effects of Abeta. CONCLUSION: beta-amyloid peptide
      reduces the level of cell membrane lipids and cholinergic receptors in human SH
      SY5Y neuroblastoma cells, likely through the induction of an enhanced oxidative
      stress.

PMID- 16608649
TI  - [Expression of osteopontin mRNA and OCT2 mRNA in human gastric carcinoma by
      tissue microarray and its significance].

PMID- 16608650
TI  - [Molecular genetics of dermatofibrosarcoma protuberans: an update].

PMID- 16608651
TI  - [Demonstration of Charcot-Leyden crystals by acid-fast stains applied on
      tissues].

PMID- 16608652
TI  - [Recent advances on p53 gene therapy].

PMID- 16608653
TI  - [Application of chromogenic in-situ hybridization in detecting HER-2/neu oncogene
      expression in breast carcinoma and its significance].

PMID- 16608654
TI  - [Pathology informatics].

PMID- 16608655
TI  - [Primary cutaneous histiocytic sarcoma].

PMID- 16608656
TI  - [Extranodal marginal zone B-cell lymphoma of nipple: report of a case].

PMID- 16608657
TI  - [Multicystic mesothelioma of peritoneum: report of two cases].

PMID- 16608658
TI  - [Spindle epithelial tumor with thymus-like elements of thyroid].

PMID- 16608659
TI  - [Nodular lymphoid hyperplasia of lung: report of a case].

PMID- 16608660
TI  - Human genetic variability and HIV treatment response.
AB  - Access to potent antiretroviral medications greatly reduces morbidity and
      mortality due to HIV/AIDS, but drug toxicity limits treatment success in many
      individuals. The field of pharmacogenomics strives to understand the influence of
      human genetic variants in response to medications. Investigators have begun to
      identify associations among human genetic variants, predisposition to HIV drug
      toxicities, and likelihood of virologic response. These include associations
      among abacavir hypersensitivity reactions, HLA type, and hsp70-hom genotypes, and
      among CYP2B6 polymorphisms, efavirenz pharmacokinetics, and central nervous
      system symptoms. Pharmacogenomics also holds great promise to suggest novel
      targets for drug development. The discovery that a naturally occurring,
      nonfunctional variant of the HIV receptor gene CCR5 protected against HIV
      infection encouraged the development of CCR5 antagonists. Through continued
      translational and applied research, pharmacogenomics will ultimately benefit
      persons living with HIV worldwide by identifying new therapeutic targets and
      through individualized drug prescribing that is informed by human genetic
      testing.

PMID- 16608661
TI  - Update: preventing mother-to-child transmission of HIV.
AB  - The success of antiretroviral therapies for prevention of mother-to-child
      transmission of HIV in the developed world has prompted a wide array of research
      efforts, from improved implementation of voluntary counseling and testing
      programs to innovative approaches for short-course peripartum prophylaxis to
      understanding the dynamics of HIV transmission via breastfeeding. Clinical trials
      of modified short-course peripartum regimens which are applicable to resource
      limited areas are demonstrating much lower transmission rates and preliminary
      data are emerging on limiting transmission via breastfeeding. Some of the most
      recent data on these topics are reviewed. Primary prevention of HIV in women of
      childbearing age combined with efforts to prevent mother-to-child transmission of
      HIV offer the best hope for addressing the burden of HIV in women and children.

PMID- 16608662
TI  - When to start antiretroviral therapy.
AB  - The current literature is controversial in providing evidence to determine the
      optimal time to initiate therapy among patients with HIV. However, there is
      evidence that initiating early treatment might provide benefits by treating
      primary HIV infection, preserving normal immune function, suppressing HIV viral
      replication, deferring clinical progression, and reducing HIV transmission. The
      biggest challenges in initiating treatment early are issues related with long
      term management, including toxicities, adherence, and drug resistance. However,
      the availability of superior new antiretroviral drugs and simplified regimens,
      the development of effective treatment strategy, and further improvement of
      adherence through directly observed treatment are addressing the issues and
      changing the balance towards earlier treatment.

PMID- 16608663
TI  - Caring for adolescents with HIV.
AB  - Adolescents comprise a growing proportion of people diagnosed with HIV or AIDS.
      Navigating adolescence while infected with HIV presents specific challenges not
      only to the youth but to their families and caregivers. As children enter their
      teen years, they have medical, physiologic, and psychosocial issues that differ
      greatly from both younger children and young adults. These issues include the
      limited number of medications available, mental illness (especially depression),
      and psychosocial issues such as distorted body image, sexual awareness, and
      problems with family and peer relations. Many of these issues are heightened in
      this population and can be important factors that can influence adherence.
      Awareness of these issues is important for health care providers, for if they
      understand not just the illness itself, but the psychosocial issues of the
      patient they are treating, the clinician can optimize treatments and adherence,
      and help these young persons successfully transition into adulthood.

PMID- 16608664
TI  - Changing antiretroviral therapy in the setting of virologic relapse: review of
      the current literature.
AB  - Virologic relapse after initial virologic suppression remains a concern for
      patients on antiretroviral therapy (ART). Multiple factors may contribute to
      virologic relapse, including suboptimal adherence, resistance, and
      pharmacokinetic issues. The major guidelines for HIV care are in agreement that
      ART regimen change is indicated in relapse because resistance is identified, but
      the guidelines are not completely clear on the timing of regimen change. When
      relapse occurs due to resistance, patients may continue with viremia well below
      their set points, stable or increasing CD4+ counts, and clinical health for
      several years. However, delaying a switch in the treatment regimen may lead to
      the accumulation of resistance which compromises future treatment response. In
      general, a lower switch threshold is recommended for patients during relapse on
      first or second line regimens.

PMID- 16608665
TI  - Once-daily therapies for the treatment of HIV infection.
AB  - For patients initiating antiretroviral therapy, there are several well-tolerated
      once-daily regimens from which to choose. Once-daily antiretroviral therapy may
      be ideal for patient adherence and convenience. However, results of a few recent
      clinical trials exploring new once-daily regimens have shown that one cannot
      assume that any three-drug combination will be successful. Once-daily therapy
      options for treatment-experienced patients are more limited but may be successful
      depending on prior antiretroviral treatment exposure and resistance mutations.
      Current approaches to once-daily therapy include simplifying successful regimens
      and investigating novel antiretroviral agents with long half-lives.

PMID- 16608667
TI  - Hypertension: which drugs to choose for patients with cardiovascular disease.

PMID- 16608666
TI  - New antiretroviral drugs.
AB  - Despite the availability of 21 antiretroviral drugs approved for the treatment of
      HIV infection, current combination regimens remain hampered by issues of
      toxicity, convenience, cost, incomplete viral suppression, and drug resistance.
      Expansion of the currently available therapeutic options through the
      reformulation of available agents, discovery of new compounds with antiretroviral
      activity, and the exploitation of novel drug targets are critical. This review
      describes the status of new nucleoside reverse transcriptase inhibitors, non
      nucleoside reverse transcriptase inhibitors, protease inhibitors, and fusion
      inhibitors. We also summarize new classes of antiretroviral therapy in clinical
      development including the attachment inhibitors, chemokine receptor antagonists,
      integrase inhibitors, and maturation inhibitors.

PMID- 16608668
TI  - Trouble at the FDA: can we fix the problems affecting you and your patients?

PMID- 16608669
TI  - Five ways you can reduce inappropriate prescribing in the elderly: a systematic
      review.

PMID- 16608670
TI  - Left-sided back pain that won't go away.

PMID- 16608671
TI  - Balancing acts: deciding for or against antibiotics in acute respiratory
      infections.
AB  - BACKGROUND: Overprescribing of antibiotics for acute respiratory infections
      (ARIs) has contributed to antibiotic resistance. Multiple clinician, patient, and
      system-related factors contribute to the prescribing of antibiotics for ARIs;
      however, these factors do not explain how clinicians arrive at their decisions to
      prescribe antibiotics. The purpose of our study was to describe this decision
      making process. METHODS: We conducted comprehensive interviews with 21 primary
      health care clinicians practicing in a rural Western US community. Our study used
      a qualitative descriptive design informed by grounded theory, and we analyzed
      data with a constant comparative method. RESULTS: Two theoretical concepts
      emerged from the interviews: 1) individual best practice described how each
      clinician attempted to do what he or she believed to be clinically best for the
      patient presenting with acute respiratory symptoms. The second concept, perceived
      patient satisfaction, described how the clinicians endeavored to satisfy
      patients, according to their own perceptions of the patient's potential to be
      satisfied. 2) Balancing acts emerged as the basic social process and is defined
      as the process whereby clinicians weigh individual best practice against
      perceived patient satisfaction when deciding whether to prescribe antibiotics for
      patients presenting with ARIs. CONCLUSION: The results of this investigation have
      important clinical and educational implications for reducing inappropriate
      antibiotic use for ARIs. Further controlled trials are warranted.

PMID- 16608672
TI  - Obsessive-compulsive disorder: strategies for using CBT and pharmacotherapy.

PMID- 16608673
TI  - Clinical inquiries. When should a child with an undescended testis be referred to
      a urologist?

PMID- 16608674
TI  - Clinical inquiries. When are empiric antibiotics appropriate for urinary tract
      infection symptoms?

PMID- 16608675
TI  - Clinical inquiries. What is the best test to detect herpes in skin lesions?

PMID- 16608676
TI  - Clinical inquiries. What is the best way to diagnose polycystic ovarian syndrome?

PMID- 16608677
TI  - Clinical inquiries. Are oral agents effective for the treatment of verruca
      vulgaris?

PMID- 16608678
TI  - Clinical inquiries. Should we identify and treat hyperlipidemia in the advanced
      elderly?

PMID- 16608679
TI  - Where have all the cardiothoracic surgery residents gone? Placement of graduating
      residents by United States thoracic surgery training programs, 1998 to 2002.
AB  - OBJECTIVE: We studied the evolving job placement trends of graduating
      cardiothoracic surgery residents over a 5-year period from the perspective of the
      program director. METHODS: Graduate placement questionnaires were sent to program
      directors of Accreditation Council for Graduate Medical Education-accredited
      United States thoracic surgery residency programs (n = 92). Program directors
      were asked to categorize the type of job that each resident chose upon graduation
      (1998-2002). RESULTS: Of the program directors surveyed, 71.7% (66/92) responded,
      representing 76.4% (545/714) of the total graduating resident population during
      the study period. Three-year training programs constituted 24.2% (16/66) of the
      respondents and accounted for 20.2% (110/545) of the graduates. Annually,
      graduates most commonly chose private practice jobs. Between 2001 and 2002, the
      percentage of graduates entering fellowships increased (11.8% [13/110] versus
      19.1% [21/110], P = .008) as the percentage of graduates choosing private
      practice positions decreased (56.4% [62/110] versus 45.5% [50/110], P = .15). In
      total, 12.8% (70/545) of the graduates pursued fellowships, with associated
      specialty choices being: 38.6% (27/70) adult cardiac, 37.1% (26/70) congenital,
      15.7% (11/70) transplantation, and 8.6% (6/70) thoracic. There were no
      significant differences between 2-year and 3-year training program graduates in
      choice of private practice versus academic jobs. CONCLUSIONS: In 2002, a greater
      percentage of graduates chose to pursue fellowship training at the expense of
      private practice employment. This difference may in part result from fewer
      employment opportunities rather than graduate choice. Ongoing studies are needed
      to follow this trend. Annual analysis of the placement of all graduating
      residents would help to identify changes in employment.

PMID- 16608680
TI  - Comment. Pathogenic microbial ancient DNA: a problem or an opportunity?

PMID- 16608682
TI  - Evaluating bacterial pathogen DNA preservation in museum osteological
      collections.
AB  - Reports of bacterial pathogen DNA sequences obtained from archaeological bone
      specimens raise the possibility of greatly improving our understanding of the
      history of infectious diseases. However, the survival of pathogen DNA over long
      time periods is poorly characterized, and scepticism remains about the
      reliability of these data. In order to explore the survival of bacterial pathogen
      DNA in bone specimens, we analysed samples from 59 eighteenth and twentieth
      century individuals known to have been infected with either Mycobacterium
      tuberculosis or Treponema pallidum. No reproducible evidence of surviving
      pathogen DNA was obtained, despite the use of extraction and PCR-amplification
      methods determined to be highly sensitive. These data suggest that previous
      studies need to be interpreted with caution, and we propose that a much greater
      emphasis is placed on understanding how pathogen DNA survives in archaeological
      material, and how its presence can be properly verified and used.

PMID- 16608683
TI  - Serial passage of the parasite Crithidia bombi within a colony of its host,
      Bombus terrestris, reduces success in unrelated hosts.
AB  - In the wild, Bombus spp. bees may contract infections of the trypanosome parasite
      Crithidia bombi from their nestmates or from others while foraging on
      contaminated flowers. We expected that as C. bombi is transmitted repeatedly
      among related workers within a colony, the parasite population would become more
      successful in this relatively homogeneous host population and less successful in
      individuals from unrelated colonies of the same or different species. To test our
      prediction, we serially passaged cocktails of C. bombi strains through workers
      from the same colony, taking the intensity of infection in related versus
      unrelated workers as a measure of parasite success at each step in the serial
      transfer. Using a repeated measures ANOVA, we found the ability of C. bombi to
      exploit Bombus spp. hosts did not increase within a colony, but did decrease for
      infections in workers from unrelated colonies. This reduction in success is most
      likely due to a gradual loss of appropriate C. bombi strains from the infecting
      the population as the cocktail is 'filtered' during the serial passage within a
      given colony, without a corresponding increase in overall intensity of the
      surviving strains.

PMID- 16608684
TI  - Light on the moth-eye corneal nipple array of butterflies.
AB  - The outer surface of the facet lenses in the compound eyes of moths consists of
      an array of excessive cuticular protuberances, termed corneal nipples. We have
      investigated the moth-eye corneal nipple array of the facet lenses of 19 diurnal
      butterfly species by scanning electron microscopy, transmission electron
      microscopy and atomic force microscope, as well as by optical modelling. The
      nipples appeared to be arranged in domains with almost crystalline, hexagonal
      packing. The nipple distances were found to vary only slightly, ranging from
      about 180 to 240 nm, but the nipple heights varied between 0 (papilionids) and
      230 nm (a nymphalid), in good agreement with previous work. The nipples create an
      interface with a gradient refractive index between that of air and the facet lens
      material, because their distance is distinctly smaller than the wavelength of
      light. The gradient in the refractive index was deduced from effective medium
      theory. By dividing the height of the nipple layer into 100 thin slices, an
      optical multilayer model could be applied to calculate the reflectance of the
      facet lenses as a function of height, polarization and angle of incidence. The
      reflectance progressively diminished with increased nipple height. Nipples with a
      paraboloid shape and height 250 nm, touching each other at the base, virtually
      completely reduced the reflectance for normally incident light. The calculated
      dependence of the reflectance on polarization and angle of incidence agreed well
      with experimental data, underscoring the validity of the modelling. The corneal
      nipples presumably mainly function to reduce the eye glare of moths that are
      inactive during the day, so to make them less visible for predators. Moths are
      probably ancestral to the diurnal butterflies, suggesting that the reduced size
      of the nipples of most butterfly species indicates a vanishing trait. This effect
      is extreme in papilionids, which have virtually absent nipples, in line with
      their highly developed status. A similar evolutionary development can be noticed
      for the tapetum of the ommatidia of lepidopteran eyes. It is most elaborate in
      moth-eyes, but strongly reduced in most diurnal butterflies and absent in
      papilionids.

PMID- 16608685
TI  - Function of a key morphological innovation: fusion of the cichlid pharyngeal jaw.
AB  - The pharyngeal jaw of cichlids may represent a key innovation that facilitated
      their unparalleled trophic divergence. In cichlids, 'fusion' of the lower
      pharyngeal jaw (LPJ) results from suturing between the two lower
      ceratobranchials. To examine, what novel abilities a more extensively fused
      pharyngeal jaw may confer, the function of LPJ suturing was examined in Heroine
      cichlids. Greater LPJ suturing, pharyngeal jaw splitting under compression and
      the forces used to crush molluscs in the wild suggest increased LPJ fusion in the
      trophically polymorphic Herichthys minckleyi operates to strengthen the
      pharyngeal jaw. Among Heroine cichlid species, the presence of an external LPJ
      suture and feeding specialization on molluscs was evolutionarily quite variable,
      but greater LPJ fusion estimated from the amount of external suturing was highly
      correlated with molluscivory. Throughout cichlid diversification, increased
      pharyngeal jaw fusion via suturing has likely helped to reinforce the LPJ during
      pharyngeal processing thereby facilitating the ability of cichlids to exploit
      durable prey.

PMID- 16608686
TI  - Evolution of long-range myofibrillar crystallinity in insect flight muscle as
      examined by X-ray cryomicrodiffraction.
AB  - Insect flight muscle is known for its crystal-quality regularity of contractile
      protein arrangement within a sarcomere. We have previously shown by X-ray
      microdiffraction that the crystal-quality regularity in bumble-bee flight muscle
      is not confined within a sarcomere, but extends over the entire length of a
      myofibril (>1000 sarcomeres connected in series). Because of this, the whole
      myofibril may be regarded as a millimetre-long, natural single protein crystal.
      Using bright X-ray beams from a synchrotron radiation source, we examined how
      this long-range crystallinity has evolved among winged insects. We analysed >4600
      microdiffraction patterns of quick-frozen myofibrils from 50 insect species,
      covering all the major winged insect orders. The results show that the occurrence
      of such long-range crystallinity largely coincides with insect orders with
      asynchronous muscle operation. However, a few of the more skilled fliers among
      lower-order insects apparently have developed various degrees of structural
      regularity, suggesting that the demand for skillful flight has driven the lattice
      structure towards increased regularity.

PMID- 16608687
TI  - The evolution of parental care and egg size: a comparative analysis in frogs.
AB  - The evolution of parental care and egg size has attracted considerable attention
      and theoretical debate. Several different hypotheses have been proposed
      concerning the trajectories of parental care and egg size evolution and the order
      of specific evolutionary transitions. Few comparative studies have investigated
      the predictions of these hypotheses. Here, we investigate the evolutionary
      association between parental care and egg size in frogs in a phylogenetic
      context. Data on egg size and presence or absence of parental care in various
      species of frogs was gathered from the scientific literature. As a basis for our
      comparative analyses, we developed a phylogenetic supertree, by combining the
      results of multiple phylogenetic analyses in the literature using matrix
      representation parsimony. Using phylogenetic pairwise comparisons we demonstrated
      a significant association between the evolution of parental care and large egg
      size. We then used recently developed maximum likelihood methods to infer the
      evolutionary order of specific transitions. This analysis revealed that the
      evolution of large egg size typically precedes the evolution of parental care,
      rather than the reverse. We discuss the relevance of our results to previous
      hypotheses concerning the evolution of parental care and egg size.

PMID- 16608688
TI  - A host-race of the cuckoo Cuculus canorus with nestlings attuned to the parental
      alarm calls of the host species.
AB  - The common cuckoo has several host-specific races, each with a distinctive egg
      that tends to match its host's eggs. Here, we show that the host-race
      specializing on reed warblers also has a host-specific nestling adaptation. In
      playback experiments, the nestling cuckoos responded specifically to the reed
      warbler's distinctive 'churr' alarm (given when a predator is near the nest), by
      reducing begging calls (likely to betray their location) and by displaying their
      orange-red gape (a preparation for defence). When reed warbler-cuckoos were cross
      fostered and raised by two other regular cuckoo hosts (robins or dunnocks), they
      did not respond to the different alarms of these new foster-parents. Instead,
      they retained a specific response to reed warbler alarms but, remarkably,
      increased both calling and gaping. This suggests innate pre-tuning to reed
      warbler alarms, but with exposure necessary for development of the normal silent
      gaping response. By contrast, cuckoo chicks of another host-race specializing on
      redstarts showed no response to either redstart or reed warbler alarms. If host
      races are restricted to female cuckoo lineages, then chick-tuning in reed warbler
      cuckoos must be under maternal control. Alternatively, some host-races might be
      cryptic species, not revealed by the neutral genetic markers studied so far.

PMID- 16608689
TI  - Predation risk induces changes in nest-site selection and clutch size in the
      Siberian jay.
AB  - Life-history theory predicts that an individual should reduce its reproductive
      efforts by laying a smaller clutch size when high risk of nest predation reduces
      the value of current reproduction. Evidence in favour of this 'nest predation
      hypothesis', however, is scarce and based largely on correlative analyses. Here,
      we manipulated perceived risk of nest predation in the Siberian jay Perisoreus
      infaustus using playback involving a mixture of calls by corvid nest predators in
      the vicinity of nest sites. In response to being exposed to this acoustic cue
      simulating increased risk of nest predation, the jays chose a nest site offering
      more protective covering and reduced clutch size. This is the first experimental
      demonstration of clutch size adjustment and nest site selection as a result of
      phenotypic plasticity in an open nesting passerine reflecting a facultative
      response to the perceived risk of nest predation.

PMID- 16608690
TI  - Behavioural and hormonal responses to predation in female chacma baboons (Papio
      hamadryas ursinus).
AB  - In humans, bereavement is associated with an increase in glucocorticoid (GC)
      levels, though this increase can be mitigated by social support. We examined
      faecal GC levels and grooming behaviour of free-ranging female baboons to
      determine whether similar effects were also evident in a non-human species.
      Females who lost a close relative experienced a significant increase in GC levels
      in the weeks following their relative's death compared with the weeks before,
      whereas control females showed no such increase. Despite the fact that females
      concentrate much of their grooming on close kin, females who lost a close female
      relative did not experience a decrease in grooming rate and number of grooming
      partners; instead, both grooming rate and number of grooming partners increased
      after a relative's death. While the death of a close relative was clearly
      stressful over the short term, females appeared to compensate for this loss by
      broadening and strengthening their grooming networks. Perhaps as a result,
      females' GC levels soon returned to baseline. Even in the presence of familiar
      troop-mates and other relatives, females experienced a stress response when they
      lost specific companions, and they apparently sought to alleviate it by
      broadening and strengthening their social relationships.

PMID- 16608691
TI  - Male-male pheromone signalling in a lekking Drosophila.
AB  - Interest in sex pheromones has mainly been focused on mate finding, while
      relatively little attention has been given to the role of sex pheromones in mate
      choice and almost none to competition over mates. Here, we study male response to
      male pheromones in the lekking Drosophila grimshawi, where males deposit long
      lasting pheromone streaks that attract males and females to the leks and
      influence mate assessment. We used two stocks of flies and both stocks adjusted
      their pheromone depositing behaviour in response to experimental manipulation,
      strongly indicating male ability to distinguish between competitors from
      qualitative differences in pheromone streaks alone. This is the first example of
      an insect distinguishing between individual odour signatures. Pheromone
      signalling influenced competition over mates, as males adjusted their investment
      in pheromone deposition in response to foreign pheromone streaks. Both sexes
      adapt their behaviour according to information from olfactory cues in D.
      grimshawi, but the relative benefits from male-female, as compared to male-male
      signalling, remain unknown. It seems likely that the pheromone signalling system
      originally evolved for attracting females to leks. The transition to a signalling
      system for conveying information about individuals may well, however, at least in
      part have been driven by benefits from male-male signalling.

PMID- 16608692
TI  - Mating system and brain size in bats.
AB  - The contribution of sexual selection to brain evolution has been little
      investigated. Through comparative analyses of bats, we show that multiple mating
      by males, in the absence of multiple mating by females, has no evolutionary
      impact on relative brain dimension. In contrast, bat species with promiscuous
      females have relatively smaller brains than do species with females exhibiting
      mate fidelity. This pattern may be a consequence of the demonstrated negative
      evolutionary relationship between investment in testes and investment in brains,
      both metabolically expensive tissues. These results have implications for
      understanding the correlated evolution of brains, behaviour and extravagant
      sexually selected traits.

PMID- 16608693
TI  - Ancient androdioecy in the freshwater crustacean Eulimnadia.
AB  - Among the variety of reproductive mechanisms exhibited by living systems, one
      permutation--androdioecy (mixtures of males and hermaphrodites)--is distinguished
      by its rarity. Models of mating system evolution predict that androdioecy should
      be a brief stage between hermaphroditism and dioecy (separate males and females),
      or vice versa. Herein we report evidence of widespread and ancient androdioecy in
      crustaceans in the genus Eulimnadia, based on observations of over 33,000 shrimp
      from 36 locations from every continent except Antarctica. Using phylogenetic,
      biogeographical and palaeontological evidence, we infer that androdioecy in
      Eulimnadia has persisted for 24-180 million years and has been maintained through
      multiple speciation events. These results suggest that androdioecy is a highly
      successful aspect of the life history of these freshwater crustaceans, and has
      persisted for orders of magnitude longer than predicted by current models of this
      rare breeding system.

PMID- 16608694
TI  - Male monkeys remember which group members have given alarm calls.
AB  - Primates give alarm calls in response to the presence of predators. In some
      species, such as the Thomas langur (Presbytis thomasi), males only emit alarm
      calls if there is an audience. An unanswered question is whether the audience's
      behaviour influences how long the male will continue his alarm calling. We tested
      three hypotheses that might explain the alarm calling duration of male Thomas
      langurs: the fatigue, group size and group member behaviour hypotheses. Fatigue
      and group size did not influence male alarm calling duration. We found that males
      only ceased calling shortly after all individuals in his group had given at least
      one alarm call. This shows that males keep track of and thus remember which group
      members have called.

PMID- 16608695
TI  - The influence of juvenile and adult environments on life-history trajectories.
AB  - There is increasing evidence that the environment experienced early in life can
      strongly influence adult life histories. It is largely unknown, however, how past
      and present conditions influence suites of life-history traits regarding major
      life-history trade-offs. Especially in animals with indeterminate growth, we may
      expect that environmental conditions of juveniles and adults independently or
      interactively influence the life-history trade-off between growth and
      reproduction after maturation. Juvenile growth conditions may initiate a feedback
      loop determining adult allocation patterns, triggered by size-dependent mortality
      risk. I tested this possibility in a long-term growth experiment with
      mouthbrooding cichlids. Females were raised either on a high-food or low-food
      diet. After maturation half of them were switched to the opposite treatment,
      while the other half remained unchanged. Adult growth was determined by current
      resource availability, but key reproductive traits like reproductive rate and
      offspring size were only influenced by juvenile growth conditions, irrespective
      of the ration received as adults. Moreover, the allocation of resources to growth
      versus reproduction and to offspring number versus size were shaped by juvenile
      rather than adult ecology. These results indicate that early individual history
      must be considered when analysing causes of life-history variation in natural
      populations.

PMID- 16608696
TI  - Environmental variability and the initiation of dispersal: turbulence strongly
      increases seed release.
AB  - Dispersal is a critical process in ecology. It is an important biological driver
      of, for example, invasions, metapopulation dynamics, spatial pattern formation
      and pathogen movement. Much is known about the effect of environmental
      variability, including turbulence, on dispersal of diaspores. Here, we document
      experimentally the strong but under-explored influence of turbulence on the
      initiation of dispersal. Flower heads of two thistle species (Carduus nutans and
      Carduus acanthoides) with ripe seeds were exposed to series of laminar and
      turbulent air flows of increasing velocity in a wind tunnel. Seed release
      increased with wind speeds for both laminar and turbulent flows for both species.
      However, far more seeds were released, at significantly lower wind speeds, during
      turbulent flows. These results strongly suggest a need for more quantitative
      studies of abscission in the field, as well as dispersal models that incorporate
      variability in the diaspore release phase.

PMID- 16608697
TI  - Coincident scales of forest feedback on climate and conservation in a diversity
      hot spot.
AB  - The dynamic relationship between vegetation and climate is now widely
      acknowledged. Climate influences the distribution of vegetation; and through a
      number of feedback mechanisms vegetation affects climate. This implies that land
      use changes such as deforestation will have climatic consequences. However, the
      spatial scales at which such feedbacks occur remain largely unknown. Here, we use
      a large database of precipitation and tree cover records for an area of the
      biodiversity-rich Atlantic forest region in south eastern Brazil to investigate
      the forest-rainfall feedback at a range of spatial scales from ca 10(1)-10(4)
      km2. We show that the strength of the feedback increases up to scales of at least
      10(3) km2, with the climate at a particular locality influenced by the pattern of
      landcover extending over a large area. Thus, smaller forest fragments, even if
      well protected, may suffer degradation due to the climate responding to land-use
      change in the surrounding area. Atlantic forest vertebrate taxa also require
      large areas of forest to support viable populations. Areas of forest of ca 10(3)
      km2 would be large enough to support such populations at the same time as
      minimizing the risk of climatic feedbacks resulting from deforestation.

PMID- 16608698
TI  - Mathematical models in physiology.
AB  - Computational modelling of biological processes and systems has witnessed a
      remarkable development in recent years. The search-term (modelling OR modeling)
      yields over 58000 entries in PubMed, with more than 34000 since the year 2000:
      thus, almost two-thirds of papers appeared in the last 5-6 years, compared to
      only about one-third in the preceding 5-6 decades. The development is fuelled
      both by the continuously improving tools and techniques available for bio
      mathematical modelling and by the increasing demand in quantitative assessment of
      element inter-relations in complex biological systems. This has given rise to a
      worldwide public domain effort to build a computational framework that provides a
      comprehensive theoretical representation of integrated biological function-the
      Physiome. The current and next issues of this journal are devoted to a small sub
      set of this initiative and address biocomputation and modelling in physiology,
      illustrating the breadth and depth of experimental data-based model development
      in biological research from sub-cellular events to whole organ simulations.

PMID- 16608699
TI  - Modulatory effect of calmodulin-dependent kinase II (CaMKII) on sarcoplasmic
      reticulum Ca2+ handling and interval-force relations: a modelling study.
AB  - We hypothesize that slow inactivation of Ca2+/calmodulin-dependent kinase II
      (CaMKII) and its modulatory effect on sarcoplasmic reticulum (SR) Ca2+ handling
      are important for various interval-force (I-F) relations, in particular for the
      beat interval dependency in transient alternans during the decay of post
      extrasystolic potentiation. We have developed a mathematical model of a single
      cardiomyocyte to integrate various I-F relations, including alternans, by
      incorporating a conceptual CaMKII kinetics model into the SR Ca2+ handling model.
      Our model integrates I-F relations, such as the beat interval-dependent twitch
      force duration, restitution and potentiation, positive staircase phenomenon and
      alternans. We found that CaMKII affects more or less all I-F relations, and it is
      a key factor for integration of the various I-F relations in our model. Alternans
      arises, in the model, out of a steep relation between SR Ca2+ load and release,
      owing to SR load-dependent changes in the releasability of Ca2+ via the ryanodine
      receptor. Beat interval-dependent CaMKII activity, owing to its kinetic
      properties and amplifying effect on SR Ca2+ load dependency of Ca2+ release,
      replicated the beat interval dependency of alternans, as observed experimentally.
      Additionally, our model enabled reproduction of the effects of various
      interventions on alternans, such as the slowing or accelerating of Ca2+ release
      and/or uptake. We conclude that a slow time-dependent factor, represented in the
      model by CaMKII, is important for the integration of I-F relations, including
      alternans, and that our model offers a useful tool for further analysis of the
      roles of integrative Ca2+ handling in myocardial I-F relations.

PMID- 16608700
TI  - A mathematical model of pacemaker activity recorded from mouse small intestine.
AB  - The pacemaker activity of interstitial cells of Cajal (ICCs) has been known to
      initiate the propagation of slow waves along the whole gastrointestinal tract
      through spontaneous and repetitive generation of action potentials. We studied
      the mechanism of the pacemaker activity of ICCs in the mouse small intestine and
      tested it using a mathematical model. The model includes ion channels, exchanger,
      pumps and intracellular machinery for Ca2+ regulation. The model also
      incorporates inositol 1,4,5-triphosphate (IP3) production and IP3-mediated Ca2+
      release activities. Most of the parameters were obtained from the literature and
      were modified to fit the experimental results of ICCs from mouse small intestine.
      We were then able to compose a mathematical model that simulates the pacemaker
      activity of ICCs. The model generates pacemaker potentials regularly and
      repetitively as long as the simulation continues. The frequency was set at 20
      min(-1) and the duration at 50% repolarization was 639 ms. The resting and
      overshoot potentials were -78 and +1.2 mV, respectively. The reconstructed
      pacemaker potentials closely matched those obtained from animal experiments. The
      model supports the idea that cyclic changes in [Ca2+]i and [IP3] play key roles
      in the generation of ICC pacemaker activity in the mouse small intestine.

PMID- 16608701
TI  - Modelling transcriptional feedback loops: the role of Gro/TLE1 in Hes1
      oscillations.
AB  - The transcriptional repressor Hes1, a basic helix-loop-helix family protein,
      periodically changes its expression in the presomitic mesoderm. Its periodic
      pattern of expression is retained in a number of cultured murine cell lines. In
      this paper, we introduce an extended mathematical model for Hes1 oscillatory
      expression that includes regulation of Hes1 transcription by Drosophila Groucho
      (Gro) or its vertebrate counterpart, the transducine-like enhancer of
      split/Groucho-related gene product 1 (TLE1). Gro/TLE1 is a necessary corepressor
      required by a number of DNA-binding transcriptional repressors, including Hes1.
      Models of direct repression via Hes1 typically display an expression overshoot
      after transcription initiation which is not seen in the experimental data.
      However, numerical simulation and theoretical predictions of our model show that
      the cofactor Gro/TLE1 reduces the overshoot and is thus necessary for a rapid and
      finely tuned response of Hes1 to activation signals. Further, from detailed
      linear stability and numerical bifurcation analysis and simulations, we conclude
      that the cooperativity coefficient (h) for Hes1 self-repression should be large
      (i.e. h>or=4). Finally, we introduce the characteristic turnaround duration, and
      show that for our model the duration of the repression loop is between 40 and 60
      min.

PMID- 16608702
TI  - Acidosis in models of cardiac ventricular myocytes.
AB  - The effects of acidosis on cardiac electrophysiology and excitation-contraction
      coupling have been studied extensively. Acidosis decreases the strength of
      contraction and leads to altered calcium transients as a net result of complex
      interactions between protons and a variety of intracellular processes. The
      relative contributions of each of the changes under acidosis are difficult to
      establish experimentally, however, and significant uncertainties remain about the
      key mechanisms of impaired cardiac function. In this paper, we review the
      experimental findings concerning the effects of acidosis on the action potential
      and calcium handling in the cardiac ventricular myocyte, and we present a
      modelling study that establishes the contribution of the different effects to
      altered Ca2+ transients during acidosis. These interactions are incorporated into
      a dynamical model of pH regulation in the myocyte to simulate respiratory
      acidosis in the heart.

PMID- 16608703
TI  - The functional role of cardiac T-tubules explored in a model of rat ventricular
      myocytes.
AB  - The morphology of the cardiac transverse-axial tubular system (TATS) has been
      known for decades, but its function has received little attention. To explore the
      possible role of this system in the physiological modulation of electrical and
      contractile activity, we have developed a mathematical model of rat ventricular
      cardiomyocytes in which the TATS is described as a single compartment. The
      geometrical characteristics of the TATS, the biophysical characteristics of ion
      transporters and their distribution between surface and tubular membranes were
      based on available experimental data. Biophysically realistic values of mean
      access resistance to the tubular lumen and time constants for ion exchange with
      the bulk extracellular solution were included. The fraction of membrane in the
      TATS was set to 56%. The action potentials initiated in current-clamp mode are
      accompanied by transient K+ accumulation and transient Ca2+ depletion in the TATS
      lumen. The amplitude of these changes relative to external ion concentrations was
      studied at steady-state stimulation frequencies of 1-5 Hz. Ca2+ depletion
      increased from 7 to 13.1% with stimulation frequency, while K+ accumulation
      decreased from 4.1 to 2.7%. These ionic changes (particularly Ca2+ depletion)
      implicated significant decrease of intracellular Ca2+ load at frequencies natural
      for rat heart.

PMID- 16608704
TI  - Contributions of inwardly rectifying K+ currents to repolarization assessed using
      mathematical models of human ventricular myocytes.
AB  - Repolarization of the action potential (AP) in cardiac muscle is a major
      determinant of refractoriness and excitability, and can also strongly modulate
      excitation-contraction coupling. In clinical cardiac electrophysiology, the Q-T
      interval, and hence action potential duration, is both an essential marker of
      normal function and an indicator of risk for arrhythmic events. It is now well
      known that the termination of the plateau phase of the AP and the repolarization
      waveform involve a complex interaction of transmembrane ionic currents. These
      include a slowly inactivating Na+ current, inactivating Ca2+ current, the decline
      of an electrogenic current due to Na+/Ca2+ exchange and activation of three or
      four different K+ currents. At present, many of the quantitative aspects of this
      important physiological and pathophysiological process remain incompletely
      understood. Recently, three mathematical models of the membrane AP in human
      ventricle myocyte have been developed and made available on the Internet. In this
      study, we have implemented these models for the purpose of comparing the K+
      currents, which are responsible for terminating the plateau phase of the AP and
      generating its repolarization. In this paper, our emphasis is on the two highly
      nonlinear inwardly rectifying potassium currents, (IK1) and (IK,r). A more
      general goal is to obtain improved understanding of the ionic mechanisms, which
      underlie all-or-none repolarization and the parameter denoted 'repolarization
      reserve' in the human ventricle. Further, insights into these fundamental
      variables can be expected to provide a more rational basis for clinical
      assessment of the Q-T and Q-TC intervals, and hence provide insights into some of
      the very substantial efforts in safety pharmacology, which are based on these
      parameters.

PMID- 16608705
TI  - Simulation of Ca2+-activated Cl- current of cardiomyocytes in rabbit pulmonary
      vein: implications of subsarcolemmal Ca2+ dynamics.
AB  - In recent studies, we recorded transiently activated outward currents by the
      application of three-step voltage pulses to induce a reverse mode of Na+-Ca2+
      exchange (NCX). We found that these currents were mediated by a Ca2+-activated Cl
      current. Based on the recent reports describing the atrial Ca2+ transients, the
      Ca2+ transient at the subsarcolemmal space was initiated and then diffused into
      the cytosolic space. Because the myocardium in the pulmonary vein is an extension
      of the atrium, the Ca2+-activated Cl- current may reflect the subsarcolemmal Ca2+
      dynamics. We tried to predict the subsarcolemmal Ca2+ dynamics by simulating
      these current traces. According to recent reports on the geometry of atrial
      myocytes, we assumed that there were three compartments of sarcoplasmic reticulum
      (SR): a network SR, a junctional SR and a central SR. Based on these structures,
      we also divided the cytosolic space into three compartments: the junctional,
      subsarcolemmal and cytosolic spaces. Geometry information and cellular
      capacitance suggested that there were essentially no T-tubules in these cells.
      The basic physical data, such as the compartmental volumes, the diffusion
      coefficients and the stability coefficients of the Ca2+ buffers, were obtained
      from the literature. In the simulation, we incorporated the NCX, the L-type Ca2+
      channel, the rapid activating outward rectifier K+ channel, the Na+-K+ pump, the
      SR Ca2+-pump, the ryanodine receptor, the Ca2+-activated Cl- channel and the
      dynamics of Na+, K+, Ca2+ and Cl-. In these conditions, we could successfully
      reconstruct the Ca2+-activated Cl- currents. The simulation allowed estimation of
      the Ca2+ dynamics of each compartment and the distribution of the Ca2+-activated
      Cl- channel and the NCX in the sarcolemma on the junctional or subsarcolemmal
      space.

PMID- 16608706
TI  - Modelling Cl- homeostasis and volume regulation of the cardiac cell.
AB  - We aim at introducing a Cl- homeostasis to the cardiac ventricular cell model
      (Kyoto model), which includes the sarcomere shortening and the mitochondria
      oxidative phosphorylation. First, we examined mechanisms underlying the cell
      volume regulation in a simple model consisting of Na+/K+ pump, Na+-K+-2Cl-
      cotransporter 1 (NKCC1), cystic fibrosis transmembrane conductance regulator,
      volume-regulated Cl- channel and background Na+, K+ and Cl- currents. The high
      intracellular Cl- concentration of approximately 30 mM was achieved by the
      balance between the secondary active transport via NKCC1 and passive currents.
      Simulating responses to Na+/K+ pump inhibition revealed the essential role of
      Na+/K+ pump in maintaining the cellular osmolarity through creating the negative
      membrane potential, which extrudes Cl- from a cell, confirming the previous model
      study in the skeletal muscle. In addition, this model well reproduced the
      experimental data such as the responses to hypotonic shock in the presence or
      absence of beta-adrenergic stimulation. Finally, the volume regulation via Cl-
      homeostasis was successfully incorporated to the Kyoto model. The steady state
      was well established in the comprehensive cell model in respect to both the
      intracellular ion concentrations and the shape of the action potential, which are
      all in the physiological range. The source code of the model, which can reproduce
      every result, is available from http://www.sim-bio.org/.

PMID- 16608707
TI  - Modelling the onset of Type 1 diabetes: can impaired macrophage phagocytosis make
      the difference between health and disease?
AB  - A wave of apoptosis (programmed cell death) occurs normally in pancreatic beta
      cells of newborn mice. We previously showed that macrophages from non-obese
      diabetic (NOD) mice become activated more slowly and engulf apoptotic cells at a
      lower rate than macrophages from control (Balb/c) mice. It has been hypothesized
      that this low clearance could result in secondary necrosis, escalating
      inflammation and self-antigen presentation that later triggers autoimmune, Type 1
      diabetes (T1D). We here investigate whether this hypothesis could offer a
      reasonable and parsimonious explanation for onset of T1D in NOD mice. We quantify
      variants of the Copenhagen model (Freiesleben De Blasio et al. 1999 Diabetes 48,
      1677), based on parameters from NOD and Balb/c experimental data. We show that
      the original Copenhagen model fails to explain observed phenomena within a
      reasonable range of parameter values, predicting an unrealistic all-or-none
      disease occurrence for both strains. However, if we take into account that, in
      general, activated macrophages produce harmful cytokines only when engulfing
      necrotic (but not apoptotic) cells, then the revised model becomes qualitatively
      and quantitatively reasonable. Further, we show that known differences between
      NOD and Balb/c mouse macrophage kinetics are large enough to account for the fact
      that an apoptotic wave can trigger escalating inflammatory response in NOD, but
      not Balb/c mice. In Balb/c mice, macrophages clear the apoptotic wave so
      efficiently, that chronic inflammation is prevented.

PMID- 16608708
TI  - Asymptotic properties of mathematical models of excitability.
AB  - We analyse small parameters in selected models of biological excitability,
      including Hodgkin-Huxley (Hodgkin & Huxley 1952 J. Physiol.117, 500-544) model of
      nerve axon, Noble (Noble 1962 J. Physiol.160, 317-352) model of heart Purkinje
      fibres and Courtemanche et al. (Courtemanche et al. 1998 Am. J. Physiol.275, H301
      H321) model of human atrial cells. Some of the small parameters are responsible
      for differences in the characteristic time-scales of dynamic variables, as in the
      traditional singular perturbation approaches. Others appear in a way which makes
      the standard approaches inapplicable. We apply this analysis to study the
      behaviour of fronts of excitation waves in spatially extended cardiac models.
      Suppressing the excitability of the tissue leads to a decrease in the propagation
      speed, but only to a certain limit; further suppression blocks active propagation
      and leads to a passive diffusive spread of voltage. Such a dissipation may happen
      if a front propagates into a tissue recovering after a previous wave, e.g. re
      entry. A dissipated front does not recover even when the excitability restores.
      This has no analogy in FitzHugh-Nagumo model and its variants, where fronts can
      stop and then start again. In two spatial dimensions, dissipation accounts for
      breakups and self-termination of re-entrant waves in excitable media with
      Courtemanche et al. kinetics.

PMID- 16608709
TI  - The role of heterogeneities and intercellular coupling in wave propagation in
      cardiac tissue.
AB  - Electrical heterogeneities play a role in the initiation of cardiac arrhythmias.
      In certain pathological conditions such as ischaemia, current sinks can develop
      in the diseased cardiac tissue. In this study, we investigate the effects of
      changing the amount of heterogeneity and intercellular coupling on wavefront
      stability in a cardiac cell culture system and a mathematical model of excitable
      media. In both systems, we observe three types of behaviour: plane wave
      propagation without breakup, plane wave breakup into spiral waves and plane wave
      block. In the theoretical model, we observe a linear decrease in propagation
      velocity as the number of heterogeneities is increased, followed by a rapid,
      nonlinear decrease to zero. The linear decrease results from the heterogeneities
      acting independently on the wavefront. A general scaling argument that considers
      the degree of system heterogeneity and the properties of the excitable medium is
      used to derive a dimensionless parameter that describes the interaction of the
      wavefront with the heterogeneities.

PMID- 16608710
TI  - Endogenous driving and synchronization in cardiac and uterine virtual tissues:
      bifurcations and local coupling.
AB  - Cardiac and uterine muscle cells and tissue can be either autorhythmic or
      excitable. These behaviours exchange stability at bifurcations produced by
      changes in parameters, which if spatially localized can produce an ectopic
      pacemaking focus. The effects of these parameters on cell dynamics have been
      identified and quantified using continuation algorithms and by numerical
      solutions of virtual cells. The ability of a compact pacemaker to drive the
      surrounding excitable tissues depends on both the size of the pacemaker and the
      strength of electrotonic coupling between cells within, between, and outside the
      pacemaking region. We investigate an ectopic pacemaker surrounded by normal
      excitable tissue. Cell-cell coupling is simulated by the diffusion coefficient
      for voltage. For uniformly coupled tissues, the behaviour of the hybrid tissue
      can take one of the three forms: (i) the surrounding tissue electrotonically
      suppresses the pacemaker; (ii) depressed rate oscillatory activity in the
      pacemaker but no propagation; and (iii) pacemaker driving propagations into the
      excitable region. However, real tissues are heterogeneous with spatial changes in
      cell-cell coupling. In the gravid uterus during early pregnancy, cells are weakly
      coupled, with the cell-cell coupling increasing during late pregnancy, allowing
      synchronous contractions during labour. These effects are investigated for a
      caricature uterine tissue by allowing both excitability and diffusion coefficient
      to vary stochastically with space, and for cardiac tissues by spatial gradients
      in the diffusion coefficient.

PMID- 16608713
TI  - Mainstreaming interprofessional education in the United Kingdom: a position
      paper.
AB  - Interprofessional education (IPE) is being built into the mainstream of
      professional education for all health and social care professions throughout the
      United Kingdom (UK) driven by the Labour Government elected in 1997,
      coincidentally the year that this Journal hosted the first All Together Better
      Health conference in London. The incoming government prioritized pre-qualifying
      IPE to be provided in partnership by universities and service agencies supported
      regionally by workforce development confederations, later absorbed into strategic
      health authorities (SHAs), and centrally by educational, professional and
      regulatory bodies. Ambitious agenda for pre-qualifying IPE set by government are
      being tempered by realistic assessment of current outcomes borne of experience
      and corroborated by evidence. This paper suggests some ways to ease constraints
      and improve outcomes, but emphasizes the need to generate continuing
      interprofessional learning opportunities that build on the basics. It argues that
      accumulating experience and evidence must be brought to bear in formulating
      criteria for the approval and review of IPE within regulatory systems for
      professional education. Can IPE be sustained within mainstream professional
      education once initial enthusiasm ebbs and earmarked funds run dry? That is the
      issue.

PMID- 16608714
TI  - Barriers to healthcare as reported by rural and urban interprofessional
      providers.
AB  - The research literature is replete with reports of barriers to care perceived by
      rural patients seeking healthcare. Less often reported are barriers perceived by
      the rural healthcare providers themselves. The current study is an extensive
      survey of over 1,500 healthcare providers randomly selected from two US states
      with large rural populations, Alaska and New Mexico. Barriers consistently
      identified across rural and urban regions by all healthcare professionals were
      Patient Complexity, Resource Limitations, Service Access, Training Constraints,
      and Patient Avoidance of Care. Findings confirmed that rural areas, however,
      struggle more with healthcare barriers than urban and small urban areas,
      especially as related to Resource Limitations, Confidentiality Limitations,
      Overlapping Roles, Provider Travel, Service Access, and Training Constraints.
      Almost consistently, the smaller a provider's practice community, the greater the
      reports of barriers, with the most severe barriers reported in small rural
      communities.

PMID- 16608715
TI  - Interprofessional health care teams: attitudes and environmental factors
      associated with participation by community pharmacists.
AB  - The purpose of this study was to determine whether community pharmacists are
      prepared to assume a more active role as members of the primary health care team.
      A secondary objective was to develop multi-items scales for future studies
      involving pharmacists, as well as other health professions. This paper reports on
      rates of participation by community pharmacists as members of interprofessional
      health care teams, the extent to which this participation was related to
      pharmacists' attitudes about their preparedness for this role, their relationship
      with physicians, and their assessment of potential barriers to interprofessional
      teamwork within their practice setting. A mail questionnaire was sent to
      community pharmacists across Canada between February and April, 2004. The overall
      response rate was 35.2% (470/1337) with the highest response rate in the Prairie
      Provinces (40.6%) and the lowest in Quebec (24.4%). Pharmacists on teams were
      more likely to agree their training and skills were sufficient to participate,
      and to report good relations with physicians. Pharmacists on teams were more
      likely to agree there was more opportunity to meet and get to know other health
      disciplines, and to see teamwork as part of their role. They were also more
      likely to agree physicians wanted their input, and less likely to see other
      disciplines as being too protective of their professional "turf". Pharmacists on
      teams did not differ from those not on teams in rating lack of time, bad past
      experiences with teamwork, financial reimbursement or proximity to other health
      care workers as barriers to being a member of a community-based primary care
      team.

PMID- 16608716
TI  - Finding solutions to challenges faced in community-based participatory research
      between academic and community organizations.
AB  - Partnerships between communities and academic institutions have been vital in
      addressing complex health and psychosocial issues faced by culturally diverse and
      hard-to-reach populations. Community-based participatory research (CBPR) has been
      suggested as a strategy to develop trust and build on the strengths of partners
      from various settings to address significant health issues, particularly those
      persistent health issues that reveal disparities among minority populations.
      There have been many challenges to developing these partnerships in the United
      States. The purpose of this paper is to discuss approaches and solutions used by
      this research team in response to the challenges they have faced in using CBPR.
      The team uses CBPR to understand and support the process of disclosure of
      intimate partner violence (IPV) within the context of the community health
      centers that provide services for multicultural and multi-lingual populations.
      While CBPR provides a route to develop trust and build on the strengths of
      partners from various settings, there are multiple challenges that arise when
      partnering organizations present with different infrastructures, missions,
      resources and populations served. Examples of common challenges and solutions
      from the literature and from the team's experience will be discussed.
      Implications for partners, partnerships, practice and research will be explored.

PMID- 16608717
TI  - Outcomes of interprofessional education for Community Mental Health Services in
      England: the longitudinal evaluation of a postgraduate programme.
AB  - We report a comprehensive, longitudinal evaluation of a two-year, part-time
      postgraduate programme designed to enable health and social care professionals in
      England to work together to deliver new community mental health services,
      including psychosocial interventions (PSIs). The study tracked three successive
      cohorts of students (N = 111) through their learning. Outcomes were assessed
      according to the Kirkpatrick/Barr et al. framework using a mixed methodology,
      which employed both quantitative measures and interviews. The students evaluated
      the programme positively and appreciated its focus on interprofessional learning
      and partnership with services users, but mean levels of stress increased and
      almost one quarter dropped out. There was considerable evidence of professional
      stereotyping but little evidence of change in these during the programme.
      Students reported substantial increases in their knowledge and skills in
      multidisciplinary team working and use of PSIs (p < 0.001). Experiences in the
      implementation of learning varied; in general, students reported significantly
      greater role conflict (p = 0.01) compared to a sample of their team colleagues (N
      = 62), but there was strong evidence from self-report measures (p < 0.001) and
      work-place interviews that the students' use of PSIs had increased. Users with
      severe mental health problems (N = 72) randomly selected from caseloads of two
      cohorts of students improved over six months in terms of their social functioning
      (p = 0.047) and life satisfaction (p = 0.014). Having controlled statistically
      for differences in baseline score, those in the intervention (programme) group
      retained a significant advantage in terms of life skills (p < 0.001) compared to
      service users in two non-intervention comparison groups (N = 133). Responses on a
      user-defined measure indicated a high level of satisfaction with students'
      knowledge, skills and personal qualities. We conclude that that there is strong
      evidence that a well-designed programme of IPE can be effective in helping
      students to learn new knowledge and skills, and to implement their learning in
      the workplace. Further, we consider that there is some modest evidence of the
      benefits of such learning for service users.

PMID- 16608718
TI  - Will opposites attract? Similarities and differences in students' perceptions of
      the stereotype profiles of other health and social care professional groups.
AB  - The extent to which health and social care (HSC) students hold stereotypical
      views of other HSC professional groups is of great potential importance to team
      working in health care. This paper explores students' perceptions of different
      HSC professional groups at the beginning of their university programmes. Findings
      are presented from an analysis of baseline data collected as part of the New
      Generation Project longitudinal cohort study which is assessing the impact of
      interprofessional education over time on a range of variables including
      stereotyping. Questionnaires were administered to a cohort of over 1200 students
      from 10 different HSC professional groups entering their first year of
      university. Stereotypes were measured using a tool adapted from Barnes et al.
      (2000) designed to elicit stereotype ratings on a range of nine characteristics.
      The findings confirm that students arrive at university with an established and
      consistent set of stereotypes about other health and social care professional
      groups. Stereotypical profiles were compiled for each professional group
      indicating the distinctive characteristics of the groups as well as the
      similarities and differences between groups.Midwives, social workers and nurses
      were rated most highly on interpersonal skills and on being a team player whilst
      doctors were rated most highly on academic ability. Doctors, midwives and social
      workers were perceived as having the strongest leadership role, whilst doctors
      were also rated most highly on decision making. All professions were rated highly
      on confidence and professional competence and, with the exception of social
      workers, on practical skills. A comparison of profiles for each professional
      group reveals that, for example, pharmacists and doctors were perceived as having
      very similar characteristics as were social workers, midwives and nurses.
      However, the profiles of nurses and doctors were perceived to be very different.
      The implications of these similarities and differences are discussed in terms of
      their potential impact on interprofessional interactions, role boundaries and
      team working.

PMID- 16608719
TI  - Evaluation of a model for maximizing interprofessional education in an acute
      hospital.
AB  - A one-year planning phase established a rolling programme of bi-monthly
      interprofessional clinical teaching workshops derived directly from patient
      experiences in an acute hospital. Pre-registration healthcare students from 8
      professions spent an afternoon in the hospital training centre, randomly
      allocated to one of 6-8 small working groups. Using a problem-based methodology
      they analysed a ward case with patient consent, chosen to reflect the input of a
      wide range of health professionals. Students worked through a prepared workbook
      facilitated by a range of tutors from all disciplines. Each small group reported
      back on one aspect of team working to the entire cohort entering into debate and
      discussion with the support of clinical and academic tutors. Post course patient
      details were found on a website enabling students to progress their uni
      professional knowledge, e.g., on anatomy, physiology, pharmacology etc. The
      questionnaire evaluation on over 126 students and 11 tutors identified that
      interprofessional competencies were understood and valued. Students related
      principles of team working and collaborative practice to their placement
      experiences of team work. Interactive learning enables further appreciation of
      professions roles and responsibilities and the importance of teamwork to optimize
      patient care (82.0 - 90.5%). The half-day learning model can be easily supported
      by busy clinical staff, led by hospital educators and accessed by students on
      hospital placements, at a mid-point in training, with learning supported by
      consenting in-patients or recent admissions prepared to share their experiences.

PMID- 16608721
TI  - Interdisciplinary Journal Club: an innovative tool for the transfer of knowledge
      and the promotion of a culture of interdisciplinarity.

PMID- 16608722
TI  - Interprofessional primary care: patients' perspectives.

PMID- 16608732
TI  - Enhanced liver targeting of 5-fluorouracil using galactosylated human serum
      albumin as a carrier molecule.
AB  - The objective of this study was to develop a liver-specific antihepatocarcinoma
      agent. The galactosylated human serum albumin 5-fluorouracil conjugate (GHSA-5
      FU) was prepared and tested for its chemical characteristic, biodistribution and
      primary cytotoxicity. The matrix assisted laser desorption ionization time-of
      flight mass spectrometry (MALDI-TOF-MS) was applied to determined the molar ratio
      (moles of 5-FU/mole of G-HSA and moles of galactose/mole of HSA) of the
      conjugate. The liver targeting ability of GHSA-5-FU labeled by (131)I was
      evaluated by measuring the total radioactivity in organs after i.v.
      administration in mice and rabbits, and the cytotoxicity of the conjugate was
      assayed by MTT method. The results showed that the molar ratio of galactose to
      HSA was 50, and the 5-FU to GHSA was 15. Liver uptake in rabbits and mice peaked
      within 5-20 min after injection. The radioactivity (counts/g tissue) of the
      conjugate in the liver was several times higher than those in the other organs.
      The conjugate showed strong cytotoxicity, but no significant cytotoxicity
      difference was found between GHSA-5-FU and free 5-FU.

PMID- 16608733
TI  - Nanorobot: a versatile tool in nanomedicine.
AB  - Miniaturizing in chip technology, optics, micro mechanics, medicine, gene and
      biotechnology requires highly precise positioning techniques. The motivation for
      the new manipulation technology is the desire to enter the micro- and nanoworld
      not only by viewing but also acting, altering micro- and nanosized objects. A new
      era on medicine are expected to happen in the coming years. Due to the advances
      in the field of nanotechnology, nanodevice manufacturing has been growing
      gradually. From such achievements in nanotechnology and recent results in
      biotechnology and genetics, the first operating biological nanorobots are
      expected to appear in the coming 5 years and more complex diamondoid based
      nanorobots will become available in about 10 years. In terms of time, it means a
      very near better future with significant improvements in medicine.

PMID- 16608734
TI  - Modified poly(propylene imine) dendrimers as effective transfection agents for
      catalytic DNA enzymes (DNAzymes).
AB  - The major bottleneck in gene therapy remains the issue of delivery. In this work,
      various modified poly(propylene imine) (PPI) dendrimers are introduced as gene
      transfection agents. Commercially available PPI-dendrimers have been modified (i)
      at the exterior primary amines with acetyl groups or glycol gallate (PEG-like)
      groups, and (ii) at the interior tertiary amines with methyl iodide (MeI) or MeCl
      to produce multiple quaternized cationic sites in the core of the dendrimer. The
      prepared materials have been tested with respect to their binding capabilities to
      DNA, their toxicity in cell cultures, their in vitro transfection efficiency and
      their in vivo delivery possibilities. In all cases, a 33-mer oligonucleotide
      (DNAzyme) was used. Polyacrylamide gel electrophoresis (PAGE) studies have
      demonstrated strong but reversible binding, where the quarternized and higher
      generation dendrimer species have shown more potent binding. Typically, for the
      modified fourth PPI-dendrimers, binding is observed at a concentration of about 4
      microM DNA and a dendrimer-DNA charge ratio of around 2:1-1:1. All the tested PPI
      dendrimers display a low cellular toxicity, especially when higher serum contents
      are used in the culture medium. For example, most of the prepared fourth
      generation PPI-dendrimers are not or hardly toxic up to at least 20 microM in 20%
      serum. An in vitro characterization has revealed a high dendrimer-mediated
      intracellular uptake of the DNAzyme: all the tested fourth generation PPI
      dendrimers display transfection efficiencies close to or exceeding 80%, even when
      the concentration of serum in the medium is increased from 10 to 40%. Finally,
      the potential of using modified PPI-dendrimers for in vivo gene therapy
      experiments is demonstrated. Injecting a G4-PEG(MeI)-ssDNA complex intravenously
      into Nude mice has resulted in a high nuclear uptake as confirmed by co
      localization studies.

PMID- 16608736
TI  - Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl
      cyanoacrylate) nanoparticles after intravenous administration to glioblastoma
      bearing rats.
AB  - It was recently shown that doxorubicin (DOX) bound to polysorbate-coated
      nanoparticles (NP) crossed the intact blood-brain barrier (BBB), and thus reached
      therapeutic concentrations in the brain. Here, we investigated the
      biodistribution in the brain and in the body of poly(butyl-2-cyano[3
      (14)C]acrylate) NP ([(14)C]-PBCA NP), polysorbate 80 (PS 80)-coated [(14)C]-PBCA
      NP, DOX-loaded [(14)C]-PBCA NP in glioblastoma 101/8-bearing rats after i.v.
      injection. The biodistribution profiles and brain concentrations of radiolabeled
      NP were determined by radioactivity counting after i.v. administration in rats.
      Changes in BBB permeability after tumour inoculation were assessed by i.v.
      injection of Evans Blue solution. The accumulation of NP in the tumour site and
      in the contralateral hemisphere in glioblastoma bearing-rats probably was
      augmented by the enhanced permeability and retention effect (EPR effect) that may
      have been becoming instrumental due to the impaired BBB on the NP delivery into
      the brain. The uptake of the NP by the organs of the reticuloendothelial system
      (RES) was reduced after PS 80-coating, but the addition of DOX increased again
      the concentration of NP in the RES.

PMID- 16608735
TI  - Delivery of hydrophobised 5-fluorouracil derivative to brain tissue through
      intravenous route using surface modified nanogels.
AB  - Random copolymeric micelles composed of N-isopropylacrylamide (NIPAAM) and N
      vinylpyrrolidone (VP) cross-linked with N,N'-methylenebisacrylamide (MBA) have
      been used as nanogel carriers to encapsulate N-hexylcarbamoyl-5-fluorouracil
      (HCFU), a prodrug of 5-FU, and have been targeted to brain tissue across blood
      brain barrier (BBB) after coating with polysorbate 80. Accumulation of nanogel
      particles in the brain and other tissues of "strain A" mice had been monitored by
      radiolabeling of nanogels with (99m)Tc. Gamma Scintigraphic technique was also
      performed to see the distribution of (99m)Tc labeled nanogels in the brain. The
      retention time in blood appeared to be slightly longer for coated nanogels than
      that of uncoated nanogels though the accumulation of coated nanogels in the RES
      was more or less same as that of uncoated nanogels. The blood however had almost
      double accumulation of polysorbate 80 coated nanogels in the initial 5 min
      compared to that shown by uncoated nanogels. We speculate that coating of
      nanogels with polysorbate 80 alters the surface properties of nanogels, which
      results in relatively higher uptake in the brain tissue. The studies revealed
      that a large portion of (99m)Tc labeled HCFU loaded nanogels are accumulated in
      the RES (lung, liver and spleen). The accumulation of the labeled nanogels in the
      brain, however, is much less compared to RES and it has been found that while an
      amount of uncoated labeled nanogels was found to be 0.18% of the injected dose,
      it increased to 0.52% on coating with polysorbate 80. The optimal amount of
      polysorbate 80 added to nanogels for the maximum delivery of particles to brain
      was found to be 1% w/w. These results were further supported by the gamma
      scintigrams of New Zealand rabbits. Thus, the present nanogel system has opened a
      new avenue for poorly soluble drugs to be targeted to brain by coating the
      particles with polysorbate 80.

PMID- 16608737
TI  - Death of a president and his assassin--errors in their diagnosis and autopsies.
AB  - On July 2, 1881, Charles Julius Guiteau shot President James Abram Garfield in
      the right flank. The President died because of infection produced by the
      unsterile fingers and probes repeatedly inserted into the wound. The major
      complaint of the wounded President was intractable pain in his legs and feet.
      This symptom failed to alert the doctors to the possibility of vertebral and
      spinal cord injury. Garfield died with sepsis after 80 days of intense national
      concern, and for the patient there was psychological, physical, and nutritional
      deprivation. His autopsy revealed the bullet was not in the pelvis as his doctors
      had expected, but adjacent to the first lumbar vertebra it had shattered. The
      trial and execution of Guiteau split the medical community into those that
      considered him insane and those who felt execution was justified. Guiteau was
      delusional and his brain revealed chronic inflammation and histological features
      suggestive of syphilis. At the time, and since, the propriety of the execution
      has been questioned.

PMID- 16608738
TI  - Serendipity and the cerebral localization of pleasure.
AB  - Most accounts of the discovery of "pleasure" circuits in the brain begin with the
      observation by James Olds and Peter Milner in 1953 that electrical brain
      stimulation can condition operant responses in rats. Less well-known, pleasurable
      brain stimulation was previously observed in schizophrenic patients by Robert
      Heath. However, Heath failed to recognize the significance of this observation,
      at least in part, because of preconceived notions he held about the etiology of
      schizophrenia. This episode in the history of neuroscience illustrates the
      importance of sagacity in serendipitous scientific discoveries. It also shows
      that "mental preparedness" can be an obstacle to progress.

PMID- 16608739
TI  - Martin-Gruber and Marinacci communications--anatomic or physiologic
      consideration.

PMID- 16608740
TI  - A case of cranial surgery in the Talmud.
AB  - The history of Jewish discourse on law and philosophy was transformed from an
      oral teaching to a written teaching around the beginning of the Common Era. The
      result of these written laws and commentaries is known today as the Talmud. Many
      pages of the Talmud discuss illnesses and diseases and their potential
      treatments, however very few of these potential treatments involve invasive
      surgery. In one instance, involving a painful skin ailment called ra'aton, the
      authors of the Talmud suggest cranial surgery as the cure and describe the
      preparation of a potential anesthetic, the surgery environment, and the removal
      of a growth. Although this account raises several questions about the ailment
      itself, it provides us with a rare look at invasive cranial surgery dating back
      nearly 2,000 years.

PMID- 16608741
TI  - The Lashley Award.
AB  - The Karl Spencer Lashley Award for Distinguished Achievement in the Neurosciences
      has been bestowed upon 50 of the world's leading neuroscientists of the last half
      century but is not well known. It originated in 1953 when Lashley accumulated
      excess stock holdings and established a Fund for Neurobiology with 52,000 dollars
      to provide small grants for neurobiological research. Several years later the
      assets were transferred to the American Philosophical Society to administer and
      convert to an award for achievement in neurobiology The nature, amount, and
      format of the award have evolved ever since. These changes in the award and the
      characteristics of its recipients are described.

PMID- 16608742
TI  - Neurognostics question: an American neurophysiologist, pioneer of
      electromyography, a president of universities and scientific advisor to United
      States presidents.

PMID- 16608743
TI  - Cerebral automatism, the brain, and the soul in Bram Stoker's Dracula.
AB  - Neither literary critics nor historians of science have acknowledged the extent
      to which Bram Stoker's Dracula (1897) is indebted to late-Victorian neurologists,
      particularly David Ferrier, John Burdon-Sanderson, Thomas Huxley, and William
      Carpenter. Stoker came from a family of distinguished Irish physicians and
      obtained an M.A. in mathematics from Trinity College, Dublin. His personal
      library contained volumes on physiology, and his composition notes for Dracula
      include typewritten pages on somnambulism, trance states, and cranial injuries.
      Stoker used his knowledge of neurology extensively in Dracula. The automatic
      behaviors practiced by Dracula and his vampiric minions, such as somnambulism and
      hypnotic trance states, reflect theories about reflex action postulated by
      Ferrier and other physiologists. These scientists traced such automatic behaviors
      to the brain stem and suggested that human behavior was "determined" through the
      reflex action of the body and brain-a position that threatened to undermine
      entrenched beliefs in free will and the immortal soul. I suggest that Stoker's
      vampire protagonist dramatizes the pervasive late-nineteenth-century fear that
      human beings are soulless machines motivated solely by physiological factors.

PMID- 16608745
TI  - NEUROwords: Elpenor's syndrome: the link between one of Ulysses' companions and
      the tenth president of the Third French Republic.

PMID- 16608747
TI  - Recognizing face identity from natural and morphed smiles.
AB  - It is easier to identify a degraded familiar face when it is shown moving
      (smiling, talking; nonrigid motion), than when it is displayed as a static image
      (Knight & Johnston, 1997; Lander, Christie, & Bruce, 1999). Here we explore the
      theoretical underpinnings of the moving face recognition advantage. In Experiment
      1 we show that the identification of personally familiar faces when shown
      naturally smiling is significantly better than when the person is shown
      artificially smiling (morphed motion), as a single static neutral image or as a
      single static smiling image. In Experiment 2 we demonstrate that speeding up the
      motion significantly impairs the recognition of identity from natural smiles, but
      has little effect on morphed smiles. We conclude that the recognition advantage
      for face motion does not reflect a general benefit for motion, but suggests that,
      for familiar faces, information about their characteristic motion is stored in
      memory.

PMID- 16608748
TI  - Priming and trial spacing in extinction: effects on extinction performance,
      spontaneous recovery, and reinstatement in appetitive conditioning.
AB  - Previous research in this laboratory suggests that priming of the conditional
      stimulus (CS) in short-term memory may play a role in the trial-spacing effects
      in appetitive conditioning. For example, a non-reinforced presentation of a CS 60
      s before a reinforced trial with the same CS produced slower acquisition than a
      CS presentation that occurred 240 s before the reinforced trial. The results were
      consistent with the self-generated priming mechanism proposed by Wagner (e.g.,
      Wagner 1978, 1981). The present experiments extended the earlier work by
      examining the effects of trial spacing in extinction rather than acquisition.
      After conditioning with a mixture of intertrial intervals (ITIs), rats received
      extinction with ITIs of 60 or 240 s, longer or shorter values, or different ways
      of "chunking" extinction trials in time. Although trial spacing produced effects
      on extinction performance that were consistent with our previous research on
      acquisition, there were few long-term differences in spontaneous recovery or in
      reinstatement. Short ITIs in extinction appear to affect extinction performance
      more than they affect extinction learning. Mechanisms of trial spacing in
      conditioning and extinction are discussed.

PMID- 16608749
TI  - Forward blocking in human learning sometimes reflects the failure to encode a cue
      outcome relationship.
AB  - In two "allergist" causal judgement experiments, participants were trained with a
      blocking design (A+|AB+). The procedure allowed different food cues to be paired
      with different fictitious allergic reactions. On test, participants were asked to
      rate the causal efficacy of the target cues and to recall the particular allergic
      reaction (outcome) that had followed each cue during training. Forward blocking
      was observed on the causal judgement measure and on the outcome recall measure in
      both Experiment 1 and Experiment 2. A backward blocking contingency was also
      trained in Experiment 2 (AB+|A+). Backward blocking was not observed either on
      the causal judgement or on the outcome recall measure. The evidence from the
      recall measure suggests that forward blocking in this task results from a failure
      to encode the B-outcome relationship during training. Associative and
      nonassociative mechanisms of forward blocking are discussed.

PMID- 16608750
TI  - Implicit learning of a repeated segment in continuous tracking: a reappraisal.
AB  - Several prior studies (e.g., Shea, Wulf, Whitacre, & Park, 2001; Wulf & Schmidt,
      1997) have apparently demonstrated implicit learning of a repeated segment in
      continuous-tracking tasks. In two conceptual replications of these studies, we
      failed to reproduce the original findings. However, these findings were
      reproduced in a third experiment, in which we used the same repeated segment as
      that used in the Wulf et al. studies. Analyses of the velocity and the
      acceleration of the target suggests that this repeated segment could be easier to
      track than the random segments serving as control, accounting for the results of
      Wulf and collaborators. Overall these experiments suggest that learning a
      repeated segment in continuous-tracking tasks may be much more difficult than
      learning from a repeated sequence in conventional serial reaction time tasks. A
      possible explanation for this difference is outlined.

PMID- 16608751
TI  - The associated non-targets effect: evidence of nontarget processing at and beyond
      the level of letter recognition.
AB  - In four visual search tasks participants were asked to make a target response if
      either of two targets was present and to make a nontarget response if neither
      target was present. Some target-absent displays included only nontarget stimuli
      or features that never occurred in the same displays as targets, whereas other
      target-absent displays included nontarget stimuli or features that did sometimes
      occur with targets. Nontarget responses were reliably faster in the former case
      than in the latter. This "associated non-targets effect" indicates that non
      targets are not simply classified as non-targets but in addition are
      discriminated from one another. Current visual search models may underestimate
      the degree to which non-targets are processed during search.

PMID- 16608752
TI  - Dual-goal facilitation in Wason's 2-4-6 task: what mediates successful rule
      discovery?
AB  - The standard 2-4-6 task requires discovery of a single rule and produces success
      rates of about 20%, whereas the dual-goal (DG) version requests discovery of two
      complementary rules and elevates success to over 60%. The experiment examined two
      explanations of DG superiority: Evans' (1989) positivity-bias account, and
      Wharton, Cheng, and Wickens' (1993) goal-complementarity theory. Two DG
      conditions were employed that varied the linguistic labelling of rules (either
      positively labelled Dax vs. Med, or mixed-valence "fits" vs. "does not fit").
      Solution-success results supported the goal-complementarity theory since
      facilitation arose in both DG conditions relative to single-goal tasks,
      irrespective of the linguistic labelling of hypotheses. DG instructions also
      altered quantitative and qualitative aspects of hypothesis-testing behaviour, and
      analyses revealed the novel result that the production of at least a single
      descending triple mediates between DG instructions and task success. We propose
      that the identification of an appropriate contrast class that delimits the scope
      of complementary rules may be facilitated through the generation of a descending
      instance. Overall, our findings can best be accommodated by Oaksford and Chater's
      (1994) iterative counterfactual model of hypotheses testing, which can readily
      subsume key elements of the goal-complementarity theory.

PMID- 16608753
TI  - Evidence of immediate activation of gender information from a social role name.
AB  - Two experiments investigated whether the stereotypical gender of a character is
      encoded immediately into the discourse representation and influences later
      comprehension. In Experiment 1 people read, and were confused by, a short story
      in which an incongruity arises at the end if the gender of a character introduced
      by a social role name has been inferred. In Experiment 2 online measures
      confirmed that readers were slower to read the final clause of the passage. In
      addition, a follow-up verification question revealed that these readers did not
      immediately resolve the inconsistency by inferring the appropriate gender for the
      role term. These findings provide strong evidence for gender activation at the
      time that a role name is encoded. The implications of these results for the
      mental representation of gender information and for constraints on inference
      during text comprehension are discussed.

PMID- 16608754
TI  - Gender differences in memory for object and word locations.
AB  - It has been hypothesized that gender differences in visuo-spatial working memory
      (VSWM) are larger in tasks requiring active elaboration of the material. In the
      present study we explored this issue by using an object relocation task, with
      both verbal and visual stimuli. The involvement of active processes was
      manipulated through the type of transformation required on the stimulus and
      through the introduction of different kinds of interference. In the three
      experiments reported, participants were shown either words or cartoon object
      icons in different locations and had to relocate them in either the same format
      or in the opposite one (object icons could be transformed into words and vice
      versa). Males outperformed females in the most demanding conditions, in which
      object icons and words were presented together in the encoding phase, and both
      had to be transformed in the recall phase; or when more demanding interferences
      were used. Our data suggest that the retention strategy was similar for the two
      groups and that the gender effect is related to a selective female difficulty
      associated with the increase in active VSWM processing. These findings further
      support the hypothesized distinction between the passive and active components of
      VSWM and illustrate the role that this distinction might play in accounting for
      individual differences.

PMID- 16608755
TI  - The processing of lexical stress during visual word recognition: typicality
      effects and orthographic correlates.
AB  - Many studies that have examined reading at the single-word level have been
      restricted to the processing of monosyllabic stimuli, and, as a result, lexical
      stress has not been widely investigated. In the experiments reported here, we
      used disyllabic words and nonwords to investigate the processing of lexical
      stress during visual word recognition. In Experiments 1 and 2, we found an effect
      of stress typicality in naming and lexical decision. Typically stressed words
      (trochaic nouns and iambic verbs) elicited fewer errors than atypically stressed
      words (iambic nouns and trochaic verbs). In Experiment 3, we carried out an
      analysis of 340 word endings and found clear orthographic correlates of both
      grammatical category and lexical stress in word endings. In Experiment 4, we
      demonstrated that readers are sensitive to these cues in their processing of
      nonwords during two tasks: sentence construction and stress assignment. We
      discuss the implications of these findings with regard to psycholinguistic models
      of single-word reading.

PMID- 16608756
TI  - Lexical and semantic influences on item and order memory in immediate serial
      recognition: evidence from a novel task.
AB  - Previous studies have reported that, in contrast to the effect on immediate
      serial recall, lexical/semantic factors have little effect on immediate serial
      recognition. This has been taken as evidence that linguistic knowledge
      contributes to verbal short-term memory in a redintegrative process at recall.
      Contrary to this view, we found that lexicality, frequency, and imageability all
      influenced matching span. The standard matching span task, requiring changes in
      item order to be detected, was less susceptible to lexical/semantic factors than
      was a novel task involving the detection of phoneme order and hence item identity
      changes. Therefore, in both immediate recognition and immediate serial recall,
      lexical/semantic knowledge makes a greater contribution to item identity than to
      item order memory. Task sensitivity, and not the absence of overt recall, may
      have underpinned previous failures to show effects of these variables in
      immediate recognition. We also compared matching span for pure and unpredictable
      mixed lists of words and nonwords. Lexicality had a larger impact on immediate
      recognition for pure than for mixed lists, in line with findings for immediate
      serial recall. List composition affected the detection of phoneme but not item
      order changes in matching span; similarly, in recall, mixed lists produce more
      frequent word phoneme migrations but not migrations of entire items. These
      results point to strong similarities between immediate serial recall and
      recognition. Lexical/semantic knowledge may contribute to phonological stability
      in both tasks.

PMID- 16608757
TI  - Participant recruitment methods and statistical reasoning performance.
AB  - Optimal Bayesian reasoning performance has reportedly been elusive, and a variety
      of explanations have been suggested for this situation. In a series of
      experiments, it is demonstrated that these difficulties with replication can be
      accounted for by differences in participant-sampling methodologies. Specifically,
      the best performances are obtained with students from top-tier, national
      universities who were paid for their participation. Performance drops
      significantly as these conditions are altered regarding inducements (e.g., using
      unpaid participants) or participant source (e.g., using participants from a
      second-tier, regional university). Honours-programme undergraduates do better
      than regular undergraduates within the same university, paid participation
      creates superior performance, and top-tier university students do better than
      students from lower ranked universities. Pictorial representations (supplementing
      problem text) usually have a slight facilitative effect across these participant
      manipulations. These results indicate that studies should take account of these
      methodological details and focus more on relative levels of performance rather
      than absolute performance.

PMID- 16608759
TI  - Assessment of the impact sound in golf putting.
AB  - The influence of impact sound in putting on players' perceptions of "feel" is
      explored in this paper. Tests were conducted to investigate the impact sound
      characteristics of five different ball types using two different putter types.
      The first test studied the impact sound of purely the ball, while the second test
      investigated the influence of putter construction and impact location on impact
      sound for the different ball types. Trends were found between sound spectra peaks
      in the 2 - 4 kHz range and the compression values of the balls. In addition,
      frequency content was more dependent on putter type and impact location than on
      ball construction in the 0 - 2 kHz range. The final test employed a paired
      comparison technique to investigate players' perceptions of sharpness and
      loudness of impact sound, ball speed from the clubface and ball hardness.
      Relationships between the subjective data and the sound characteristics of the
      balls were then examined. It was found that the ball the players' perceived to
      have the sharpest and loudest sound, to feel the hardest and to come off the
      clubface the quickest also had the largest calculated values of loudness and
      sharpness and had a spectral peak at a higher frequency than the other balls.

PMID- 16608760
TI  - Goal orientations and moral identity as predictors of prosocial and antisocial
      functioning in male association football players.
AB  - The purpose of this study was to examine the effects of task and ego goal
      orientation and moral identity on prosocial and antisocial judgement and
      behaviour in football. The interaction between task and ego orientation in
      predicting these variables was also examined. Participants were 210 adult male
      footballers (age 25 +/- 6 years) competing at recreational (n = 133) and semi
      professional (n = 77) levels. They completed questionnaires measuring task and
      ego goal orientation, the importance of moral identity, prosocial and antisocial
      judgement, frequency of prosocial and antisocial behaviours in football, and
      social desirability. Regression analysis revealed no main effects for goal
      orientations and moral identity on prosocial judgement and behaviour. However, a
      significant interaction effect between task and ego orientation emerged in
      relation to prosocial judgement. Specifically, task orientation positively
      predicted prosocial judgement only at low levels of ego orientation. Ego
      orientation emerged as a positive predictor of antisocial judgement and
      behaviour, whereas moral identity negatively predicted these variables. The
      differentiation between prosocial and antisocial aspects of morality was
      supported. It was concluded that examining moral identity and interactions
      between task and ego orientation adds to our understanding of the influence of
      these variables on prosocial and antisocial functioning in sport.

PMID- 16608761
TI  - A field simulation study of the effectiveness of penalty kick strategies in
      soccer: late alterations of kick direction increase errors and reduce accuracy.
AB  - This field experiment investigated the relative merits of approaching the penalty
      kick with either a keeper-independent or keeper-dependent strategy. In the keeper
      independent strategy, the shooter selects a target location in advance and
      disregards the goalkeeper's actions during the run-up. In the keeper-dependent
      strategy, the shooter makes a decision resting on the anticipation of the
      goalkeeper's movements during the run-up. Ten intermediate-level soccer players
      shot at one of two visually specified targets to the right and left side of the
      goal. In the keeper-independent strategy condition, participants were told that
      the visually specified target would not change. In the keeper-dependent strategy
      condition, participants were told that in half of the trials the visually
      specified target would change side at different times before ball contact,
      indicating that the direction of the kick needed to be altered. The results
      showed that penalty-taking performance was apt to be less than perfect in the
      keeper-dependent strategy condition. A decrease in the time available to alter
      kick direction resulted in a higher risk of not only an incorrect but also
      inaccurate shot placement. It is concluded that anticipating the goalkeeper's
      movements may degrade penalty kick performance, mainly due to insufficient time
      to modify the kicking action.

PMID- 16608762
TI  - Fixed versus free-floating stretcher mechanism in rowing ergometers: mechanical
      aspects.
AB  - The mechanical responses (i.e. external contact forces and external power) of 25
      elite rowers to a race-pace rowing protocol were investigated on the traditional
      fixed stretcher mechanism and the more recently introduced free-floating
      stretcher mechanism rowing ergometers. Using a Rowperfect rowing ergometer for
      both conditions, external contact forces at the handle, stretcher and sliding
      seat, as well as the displacements of the handle and stretcher, were recorded.
      The external power was calculated as the product of the force and velocity data
      from both the handle and stretcher. Significant differences (P < 0.05) between
      the two conditions for each mechanical parameter were observed. The fixed
      condition showed larger maximum values for forces and external power and average
      power throughout the rowing cycle. Moreover, rowing with the fixed mechanism
      generated higher inertial forces during the transition between the propulsion and
      recovery phases, especially at the catch of the cycle. The results suggest that:
      (i) muscular coordination may differ according to the stretcher mechanism used,
      which could have an impact on the physiological adaptations of muscles; and (ii)
      the free-floating mechanism may induce lower catch and maximum values for net
      joint forces and net joint moments that could decrease the risk of injury.

PMID- 16608763
TI  - Home advantage in southern hemisphere rugby union: national and international.
AB  - This study evaluates home advantages both for national (Super 12) and
      international (Tri-nations) rugby union teams from South Africa, Australia and
      New Zealand, over the five-year period 2000 - 2004 using linear modelling. These
      home advantages are examined for statistical and practical significance, for
      variability between teams, for stability over time and for inter-correlation.
      These data reveal that the overall home advantage in elite rugby union has a mean
      of +6.7 points, and that this changes little from year to year. Closer scrutiny
      nevertheless reveals a high degree of variability. Different teams can and do
      have different home advantages, which ranges from a low of -0.7 to a high of
      +28.3 points in any one year. Furthermore, some team home advantages change up or
      down from one year to the next, by as much as -36.5 to +31.4 points at the
      extremes. There is no evidence that the stronger teams have the higher home
      advantages, or that a high home advantage leads to a superior finishing position
      in the competition.

PMID- 16608764
TI  - Effects of dynamic resistance training on fascicle length and isometric strength.
AB  - The aims of this study were to assess changes in muscle architecture, isometric
      and dynamic strength of the leg extensor muscles, resulting from dynamic
      resistance training, and the relationships between strength and muscle
      architecture variables. The participants (n = 30) were randomly assigned to one
      of two groups. The training group (n = 16; age 21.8 +/- 2.3 years, body mass 74.8
      +/- 9.2 kg, height 1.75 +/- 0.08 m) performed dynamic resistance training for 13
      weeks. The control group (n = 14; age 19.9 +/- 1.5 years, body mass 74.0 +/- 8.5
      kg, height 1.76 +/- 0.05 m) did not perform any resistance training. Maximal
      dynamic and isometric strength were tested in both groups, before and after the
      training period. The members of the training group used the free-weight squat
      lift (90 degrees ) as their training exercise. The concentric phase of the squat
      was performed explosively. Skeletal muscle architecture of the vastus lateralis
      was visualized using ultrasonography. At the end of the study, significant
      increases in vastus lateralis muscle thickness (+6.9%, P < 0.001), fascicle
      length (+10.3%, P < 0.05), one-repetition maximum (+8.2%, P < 0.05), rate of
      force development (+23.8%, P < 0.05) and average force produced in the first 500
      ms (+11.7%, P < 0.05) were seen only in the training group. Adaptations to the
      muscle architecture in the training group limited the loss of fibre force, and
      improved the capacity for developing higher velocities of contraction. The
      architectural changes in the training group were similar to those seen in studies
      where high-speed training was performed. In conclusion, dynamic resistance
      training with light loads leads to increases in muscle thickness and fascicle
      length, which might be related to a more efficient transmission of fibre force to
      the tendon.

PMID- 16608765
TI  - Assessing the limitations of the Banister model in monitoring training.
AB  - The aim of this study was to carry out a statistical analysis of the Banister
      model to verify how useful it is in monitoring the training programmes of elite
      swimmers. The accuracy, the ill-conditioning and the stability of this model were
      thus investigated. The training loads of nine elite swimmers, measured over one
      season, were related to performances with the Banister model. First, to assess
      accuracy, the 95% bootstrap confidence interval (95% CI) of parameter estimates
      and modelled performances were calculated. Second, to study ill-conditioning, the
      correlation matrix of parameter estimates was computed. Finally, to analyse
      stability, iterative computation was performed with the same data but minus one
      performance, chosen at random. Performances were related to training loads for
      all participants (R(2) = 0.79 +/- 0.13, P < 0.05) and the estimation procedure
      seemed to be stable. Nevertheless, the range of 95% CI values of the most useful
      parameters for monitoring training was wide: t(a) = 38 (17, 59), t(f) = 19 (6,
      32), t(n) = 19 (7, 35), t(g) = 43 (25, 61). Furthermore, some parameters were
      highly correlated, making their interpretation worthless. We suggest possible
      ways to deal with these problems and review alternative methods to model the
      training-performance relationships.

PMID- 16608766
TI  - Errors in judging "offside" in association football: test of the optical error
      versus the perceptual flash-lag hypothesis.
AB  - The objective of this study was to analyse the correctness of the offside
      judgements of the assistant referees during the final round of the FIFA 2002
      World Cup. We also contrasted two hypotheses to explain the errors in judging
      offside. The optical error hypothesis is based on an incorrect viewing angle,
      while the flash-lag hypothesis refers to perceptual errors associated with the
      flash-lag effect (i.e. a moving object is perceived as spatially leading its real
      position at a discrete instant signalled by a briefly flashed stimulus). Across
      all 64 matches, 337 offsides were analysed using digital video technology. The
      error percentage was 26.2%. During the first 15 min match period, there were
      significantly more errors (38.5%) than during any other 15 min interval. As
      predicted by the flash-lag effect, we observed many more flag errors (86.6%) than
      non-flag errors (13.4%). Unlike the predictions of the optical error hypothesis,
      there was no significant difference between the correct and incorrect decisions
      in terms of the positioning of the assistant referees relative to the offside
      line (0.81 and 0.77 m ahead, respectively). To reduce the typical errors in
      judging offside, alternative ways need to be considered to teach assistant
      referees to better deal with flash-lag effects.

PMID- 16608767
TI  - Segmental dynamics of soccer instep kicking with the preferred and non-preferred
      leg.
AB  - Detailed time-series of the resultant joint moments and segmental interactions
      during soccer instep kicking were compared between the preferred and non
      preferred kicking leg. The kicking motions of both legs were captured for five
      highly skilled players using a three-dimensional cinematographic technique at 200
      Hz. The resultant joint moment (muscle moment) and moment due to segmental
      interactions (interaction moment) were computed using a two-link kinetic chain
      model composed of the thigh and lower leg (including shank and foot). The
      mechanical functioning of the muscle and interaction moments during kicking were
      clearly illustrated. Significantly greater ball velocity (32.1 vs. 27.1 m . s(
      1)), shank angular velocity (39.4 vs. 31.8 rad . s(-1)) and final foot velocity
      (22.7 vs. 19.6 m . s(-1)) were observed for the preferred leg. The preferred leg
      showed a significantly greater knee muscle moment (129.9 N . m) than the non
      preferred leg (93.5 N . m), while no substantial differences were found for the
      interaction moment between the two legs (79.3 vs. 55.7 N . m). These results
      indicate that the highly skilled soccer players achieved a well-coordinated inter
      segmental motion for both the preferred and non-preferred leg. The faster leg
      swing observed for the preferred leg was most likely the result of the larger
      muscle moment.

PMID- 16608768
TI  - Measurement of maximal muscle cross-sectional area of the elbow extensors and
      flexors in children, teenagers and adults.
AB  - The aims of this study were to examine age and sex differences in elbow extensor
      and flexor anatomical muscle cross-sectional area (mCSA) measured by magnetic
      resonance imaging (MRI) and the location of maximal mCSA as a percentage of the
      distance from the distal to the proximal end of the humerus. Ninety-five
      individuals spread across the age groups 9 - 10 years, 16 - 17 years and ?21
      years participated in the study. Muscle cross-sectional area derived from the
      manual MRI tracing proved to be highly reliable in terms of limits of agreement (
      2.5 to 1.5 cm(2)) and the intraclass correlation coefficient (ICC = 0.998). A sex
      by-age group analysis of variance revealed significant effects (P < 0.01) of sex,
      group and a sex-by-group interaction, the latter reflecting a greater increase in
      males than females of upper arm mCSA from childhood to adulthood. Extensor mCSA
      was more proximal (55 +/- 6%) than that of the flexors (28 +/- 6%). A significant
      effect (P < 0.01) of group was found for location of maximal extensor mCSA,
      reflecting its more distal position with increasing age. Measurements of muscle
      size should be made at the individually determined position of maximal mCSA if
      interpreting data collected during growth and maturation, especially if the
      muscle group of interest is the elbow extensors and if different age groups are
      being monitored.

PMID- 16608770
TI  - Effects of AM3 (Inmunoferon) on increased serum concentrations of interleukin-6
      and tumour necrosis factor receptors I and II in cyclists.
AB  - The aims of this study were to examine the changes in plasma concentrations of
      inflammatory cytokines induced by training and competition in professional
      cyclists. We report the serum concentrations of interleukin-6 (IL-6), tumour
      necrosis factor alpha (TNF-a), tumour necrosis factor receptors I and II (TNFR-I
      and -II) in a prospective, randomized, double-blind trial involving the
      administration of AM3 (Inmunoferon), an oral booster immunomodulator, or placebo
      to 16 professional cyclists (n = 8 in each group) for 65 consecutive days. Serum
      was collected just before treatment began (baseline), at the end of pre
      competition training, before the mountain stage of the competition (60 days), 4 h
      after finishing this stage (62 days), and 18 h after the fifth and last day of
      competition (65 days). To determine the normal levels of cytokines and soluble
      TNF receptors, individual samples from 14 moderately trained healthy controls
      were studied. After 60 days of training, the serum concentrations of IL-6 did not
      differ significantly from those at the beginning of the study for either group of
      cyclists (placebo and AM3). A significant rise was seen in IL-6 concentrations in
      both the AM3 and placebo groups at 62 days, 4 h after finishing the mountain
      stage. The increase was significantly greater in the placebo group than in the
      AM3 group. At 65 days of treatment, 18 h after the fifth and last day of
      competition, IL-6 concentrations were similar to those recorded at the end of the
      training, but were significantly higher in the placebo group than in the AM3
      group. At the end of training, serum TNFR-I concentrations in both groups of
      cyclists were significantly lower than at baseline. The concentrations of serum
      TNFR-I and -II both 4 h after finishing the mountain stage and 18 h after the
      fifth and last day of competition were significantly higher than those recorded
      after training in both groups. Professional cycling competition is associated
      with increases in serum IL-6 and TNFR-I and -II concentrations. Inmunoferon
      treatment reduced significantly the concentrations of IL-6 but not those of TNFR
      I and -II.

PMID- 16608771
TI  - Estimation of body density based on hydrostatic weighing without head submersion
      in young Japanese adults.
AB  - This study examined a method of predicting body density based on hydrostatic
      weighing without head submersion (HWwithoutHS). Donnelly and Sintek (1984)
      developed a method to predict body density based on hydrostatic weight without
      head submersion. This method predicts the difference (D) between HWwithoutHS and
      hydrostatic weight with head submersion (HWwithHS) from anthropometric variables
      (head length and head width), and then calculates body density using D as a
      correction factor. We developed several prediction equations to estimate D based
      on head anthropometry and differences between the sexes, and compared their
      prediction accuracy with Donnelly and Sintek's equation. Thirty-two males and 32
      females aged 17-26 years participated in the study. Multiple linear regression
      analysis was performed to obtain the prediction equations, and the systematic
      errors of their predictions were assessed by Bland-Altman plots. The best
      prediction equations obtained were: Males: D(g) = -164.12X1 - 125.81X2 - 111.03X3
      + 100.66X4 + 6488.63, where X1 = head length (cm), X2 = head circumference (cm),
      X3 = head breadth (cm), X4 = head thickness (cm) (R = 0.858, R2 = 0.737, adjusted
      R2 = 0.687, standard error of the estimate = 224.1); Females: D(g) = -156.03X1 -
      14.03X2 - 38.45X3 - 8.87X4 + 7852.45, where X1 = head circumference (cm), X2 =
      body mass (g), X3 = head length (cm), X4 = height (cm) (R = 0.913, R2 = 0.833,
      adjusted R2 = 0.808, standard error of the estimate = 137.7). The effective
      predictors in these prediction equations differed from those of Donnelly and
      Sintek's equation, and head circumference and head length were included in both
      equations. The prediction accuracy was improved by statistically selecting
      effective predictors. Since we did not assess cross-validity, the equations
      cannot be used to generalize to other populations, and further investigation is
      required.

PMID- 16608772
TI  - Electroencephalographic functional equivalence during observation of action.
AB  - The purpose of this study was to examine the variability in cortical activation
      during physical air-rifle shooting and three different observation conditions.
      Elite air-rifle shooters performed a 40 shot individual match.
      Electroencephalograms were recorded from 11 active sites across the cortex during
      the final 6 s (3 x 2 s epochs) before shot release. Data collection was repeated
      while shooters watched a large-screen video of their worst shot performance from
      an internal-visual perspective when seated, standing and standing holding their
      rifle. The hypothesized differences between the three observation conditions and
      the physical shooting profile were not shown except at the left anterior temporal
      site, T5. This finding suggests that observation of performance cannot be
      differentiated clearly by posture or modified through kinetic and haptic
      afference, and that visual percepts predominate in observational functional
      equivalence. However, more functionally equivalent observation reduced the
      observation/execution variability over the temporal areas. Performer debriefs
      also identified different perceptions of physiological, psychological and
      behavioural functional equivalence associated with the different observation
      conditions. We conclude that elite performers' brains are accessed equally
      effectively during different observation conditions irrespective of some of the
      physical factors ascribed to the conditions. However, they may require more
      functionally matched conditions to attain greater equivalence in temporal areas.

PMID- 16608774
TI  - CT angiography of the coronary arteries.

PMID- 16608775
TI  - Intracardiac covered stent for transcatheter completion of the total
      cavopulmonary connection: anatomical, physiological and technical considerations.
AB  - In the present review we discuss anatomical, physiological and technical aspects
      of the interventional transcatheter deployment of intracardiac covered stent for
      completion of the total cavopulmonary connection.

PMID- 16608776
TI  - Limited usefulness of non-invasive coronary angiography with 16-detector
      multislice computer tomography at a community hospital.
AB  - OBJECTIVES: To evaluate the usefulness of coronary angiography by 16-detector
      multislice spiral computed tomography (MSCT) in community hospital outpatients.
      DESIGN: MSCT was performed at the community hospital in 157 of 218 consecutive
      outpatients with suspected significant coronary disease, before referral for
      invasive coronary angiography. RESULTS: 101 patients had interpretable MSCT
      angiograms (64 men, age 62+/-10 years, calcium score 373+/-678, heart rate 56+/-7
      beats/min, beta-blocker used by 91%). Coronary stenoses >50% were identified by
      invasive angiography in 49 patients. Only 79% of all segments could be assessed
      by MSCT due to heavy coronary calcification (12%) and blurred images (9%) in the
      remaining. By interpreting non-assessable segments as negative results 79
      patients were correctly classified by MSCT. Sensitivity, specificity, positive
      and negative predictive values at patient level was 82%, 75%, 75% and 81%. By
      interpreting non-assessable segments as positive findings, the corresponding
      values were 100%, 29%, 57% and 100%, with correct diagnoses in 63% of patients.
      CONCLUSIONS: Limited diagnostic accuracy, non-interpretable scans and radiation
      exposure restrict the usefulness of coronary MSCT in a community hospital
      setting.

PMID- 16608777
TI  - Coronary bypass graft patency cannot be determined by multidetector spiral
      computed tomography.
AB  - OBJECTIVES: Angiography by selective catheterization is the reference standard
      for coronary bypass graft patency assessment but carries a risk of serious
      complications. We have investigated whether 16-slice multidetector spiral
      computed tomography (MDCT) can substitute for selective angiography. DESIGN: Two
      to three years after coronary artery bypass grafting, 45 patients with a total of
      156 bypasses (100 single and 28 sequential grafts) were examined with both MDCT
      and conventional selective angiography on the same day. The bypasses were
      classified as patent, stenotic or occluded. RESULTS: The likelihood ratio for
      MDCT-detected occlusion was 40, reflecting a fairly high combined sensitivity and
      specificity. However, 24% of the distal anastomoses could not be evaluated by
      MDCT, mainly because of respiratory movements, artifacts due to metal clips, and
      small vessel dimensions. Moreover, seven out of 117 bypasses (6%) deemed
      evaluable by MDCT were wrongly classified by this method. CONCLUSIONS: At
      present, 16-slice MDCT cannot replace selective angiography for assessment of
      coronary bypass graft patency since 24% of bypasses could not be evaluated by
      this method, and an error rate of 6% is unacceptable.

PMID- 16608778
TI  - Modifiable risk factors have an impact on socio-economic differences in coronary
      heart disease events.
AB  - OBJECTIVES: To investigate the association of socio-economic status, defined by
      occupational class, income and education, with coronary heart disease (CHD)
      morbidity and mortality, and further to analyse to which extent modifiable risk
      factors may explain socio-economic differences in CHD risk. DESIGN: A population
      based prospective cohort study including 9,061 men and 10,211 women aged 35-64 at
      baseline who participated in a cardiovascular risk factor survey in 1982, 1987,
      1992 or 1997 in Finland. The subjects were followed for CHD events up till the
      end of 2001. Cox's proportional hazards model was used in the analysis. RESULTS:
      Male manual workers had a double risk of CHD death compared with upper-level
      employees (HR=2.00, 95% CI 1.35-2.97). This excess risk was reduced by 31% when
      adjusted for traditional cardiovascular risk factors and most of this reduction
      was due to smoking. CONCLUSIONS: Modifiable risk factors explained about a third
      of the excess CHD mortality between manual workers and upper-level employees in
      men. Among women the differences between socio-economic groups were not
      statistically significant.

PMID- 16608779
TI  - Myocardial perfusion in ST-elevation myocardial infarction treated successfully
      with primary angioplasty.
AB  - OBJECTIVES: To study myocardial perfusion in ST-elevation myocardial infarction
      (STEMI) treated successfully with primary angioplasty. Additionally, to evaluate
      the predictive value of perfusion on subsequent infarct size. DESIGN: Fifty
      patients with acute STEMI and restoration of normal epicardial flow after primary
      angioplasty were included in the study. TIMI myocardial perfusion (TMP) grades
      were determined at the end of the procedure. Contrast enhanced magnetic resonance
      imaging (MRI) including first-pass perfusion and delayed enhancement imaging were
      performed within five days and after three months. RESULTS: The patients were
      divided into two groups: A=TMP 0-1, B=TMP 2-3. The early MRI showed significantly
      reduced myocardial perfusion in the infarct zone compared to remote myocardium in
      both groups (p<0.001), but the reduction was more pronounced in group A. The
      infarct sizes were smaller (p=0.0017) and the ejection fractions higher
      (p=0.0001) in group B than in group A at follow-up. CONCLUSIONS: In STEMI, early
      impairments in myocardial perfusion were observed in spite of successful
      treatment with angioplasty. Marked early impairments in perfusion were associated
      with larger infarct sizes on MRI after three months.

PMID- 16608781
TI  - Off-pump surgery does not eliminate microalbuminuria or other markers of systemic
      inflammatory response to coronary artery bypass surgery.
AB  - OBJECTIVE: To evaluate whether off-pump surgery attenuates microalbuminuria and
      other markers of systemic inflammatory response to coronary artery bypass surgery
      as compared to surgery performed using cardiopulmonary bypass. DESIGN: Forty
      three adult patients undergoing elective coronary artery bypass grafting surgery
      were operated on with or without cardiopulmonary bypass (CPB). Microalbuminuria,
      serum C-reactive protein, and oxygenation and lung function parameters were
      measured at several time points until the first postoperative morning. RESULTS:
      The urinary albumin/creatinine ratio was low in both groups before surgery, but
      reached a maximum level at the end of CPB or just after opening the last coronary
      artery clamp in the off-pump group (p<0.05). The urinary albumin/creatinine ratio
      remained slightly elevated in both groups until the morning after the operation
      (p<0.05). There were no statistical differences between groups. Serum C-reactive
      protein remained at the initial level the evening after the operation, but
      increased by the first postoperative morning in both groups (p<0.001). The
      alveolar-arterial gradient for oxygen partial pressure rose significantly after
      the operation in the intensive care unit in both groups (p<0.0001). The shunt
      fraction of the pulmonary circulation did not change in either group.
      CONCLUSIONS: Off-pump coronary artery surgery did not prevent the acute phase
      inflammatory response measured in the present study. The acute phase inflammatory
      response after coronary artery bypass surgery is more likely a response to the
      surgical trauma itself rather than to CPB.

PMID- 16608780
TI  - Tranexamic acid reduces postoperative bleeding in off-pump coronary artery bypass
      grafting.
AB  - OBJECTIVE: Tranexamic acid (TA) reduces blood loss in coronary artery surgery
      with cardiopulmonary bypass. The present prospective study was designed to
      investigate its hemostatic effect in off-pump coronary artery bypass (OPCAB).
      METHOD: Seventy-six patients undergoing elective OPCAB were randomized into two
      groups, received TA (0.75 g loading dose before surgery and 250 mg/h during
      surgery, gross dose: 1.5 g, n=36) and saline solution (control, n=40),
      respectively. Perioperative blood samples were collected. Hematochemical
      parameters including platelet adhesion rate, D-dimer and fibrinopeptide-A (FPA)
      were analysis. Volume of blood loss, blood transfusion and other clinical data
      were recorded throughout the perioperative period. RESULTS: Cumulative blood loss
      was significantly reduced in the TA group as compared to the controls
      postoperatively (6 hrs (median [25th-75th]): TA: 200.0 [140.0-230.0] ml, CONTROL:
      225.0 [200.0-347.5.0] ml, p=0.009; 24 hrs: TA: 440.0 [270.0-605.0] ml, CONTROL:
      655.0 [500.0-920.0] ml, p<0.001). Number of patients received blood transfusion
      in each group was similar. Levels of D-dimer rose significantly after surgery,
      and were significantly lower in the TA group than that in controls. Platelet
      adhesion rate and FPA levels remained at baseline levels after the operation in
      two groups. Early clinical outcomes were similar between groups. CONCLUSION: The
      results indicated that tranexamic acid limits fibrinolysis and reduces blood loss
      after off-pump coronary artery bypass surgery.

PMID- 16608782
TI  - Cost effectiveness of local collagen-gentamicin as prophylaxis for sternal wound
      infections in different risk groups.
AB  - OBJECTIVES: In a randomized trial addition of local collagen-gentamicin in the
      sternal wound reduced the rate of sternal wound infection (SWI) to about 50%
      compared to intravenous prophylaxis alone. The aim of the present study was to
      evaluate the economic rationale for its use in every-day clinical practice. This
      includes the question whether high-risk groups that may have particular benefit
      should be identified. DESIGN: For each patient with SWI in the trial the costs
      attributable to the SWI were calculated. Risk factors for SWI were identified and
      any heterogeneity of the effect of the prophylaxis examined. RESULTS: The mean
      cost of a SWI was about 14500 Euros. A cost effectiveness analysis showed that
      the prophylaxis was cost saving. The positive net balance was even higher in risk
      groups. Assignment to the control group, overweight, diabetes, younger age,
      mammarian artery use, left ventricular ejection fraction <35% and longer
      operation time were independent risk factors for infection. CONCLUSION: The
      addition of local collagen-gentamicin to intravenous antibiotic prophylaxis was
      dominant, i.e. resulted in both lower costs and fewer wound infections.

PMID- 16608783
TI  - Distant metastasis of parotid gland tumors.
AB  - The incidence of distant metastasis in head and neck cancer and especially in
      salivary gland cancer is relatively low in comparison to other malignancies.
      However, the presence of distant metastasis heralds a poor prognosis in head and
      neck cancer, with a median survival of 4.3-7.3 months. Treatment of these
      patients is usually performed in a palliative setting. Patients with malignant
      salivary gland tumors should have an X-ray or CT scan of the chest at their
      initial assessment to exclude the possibility of distant metastasis. The
      likelihood of developing distant metastasis is associated with high-grade tumors,
      such as adenoid cystic carcinoma, salivary duct carcinoma, high-grade
      mucoepidermoid carcinoma and tumors located in the submandibular gland, posterior
      tongue and pharyngeal tumors. A lower risk of developing distant metastasis is
      known for all other histological entities of salivary gland tumors. Nevertheless
      all patients who have a histologically confirmed malignant salivary gland tumor
      should have lifelong follow-up. On the basis of a clinical case regarding a
      patient with metastatic parotid gland cancer we present a review of the
      literature.

PMID- 16608784
TI  - Molecular analyses of KCNQ1-5 potassium channel mRNAs in rat and guinea pig inner
      ears: expression, cloning, and alternative splicing.
AB  - CONCLUSION: Expression of neuronal Kcnq gene family transcripts in the inner ear
      provides further evidence for cochlear M-type currents and for complex molecular
      heterogeneities of voltage-gated potassium channels composed of various KCNQ
      subunits and/or alternative splice variants. Furthermore, important roles in
      regulation of cellular excitability in the auditory system, and hearing disorders
      related to (hyper)excitability, e.g. tinnitus, are implied. BACKGROUND: Voltage
      gated potassium channels play key roles in hearing, as evidenced by deafness
      resulting from disruption of genes encoding, for example, KCNQ1 or KCNQ4
      subunits. Other members of the Kcnq gene family (Kcnq2, 3, and 5) are the
      molecular correlates of M currents, which regulate neuronal excitability. The
      expression of the latter has not previously been thoroughly investigated in the
      inner ear. OBJECTIVE: The aim of this study was to identify genetic correlates of
      M currents, previously identified in cochlear hair cells by electrophysiological
      methods. MATERIALS AND METHODS: Expression of Kcnq genes was investigated by
      reverse transcription-polymerase chain reaction (RT-PCR) using subtype-specific
      primers with total RNA isolated from whole guinea pig or rat cochlea as template.
      PCR products were confirmed by direct DNA sequencing. RESULTS: All members of the
      Kcnq family were expressed in guinea pig and rat cochlea. Cochlear expression of
      Kcnq2 exhibited two alternatively spliced forms, lacking exons 8, 15a, and 8,
      12a, 15a, respectively. Novel molecular sequence data, e.g. guinea pig Kcnq cDNA
      sequences, were deposited in GenBank (AY684985-AY684990).

PMID- 16608785
TI  - Malleus head fixation: histopathology revisited.
AB  - CONCLUSIONS: Malleus head fixation is a rare but not exceptional pathology. It
      may be apparently congenital or acquired, and can be associated with stapes
      fixation. In the acquired secondary process two histological types of malleus
      head fixation were found: the first corresponded to non-tympanosclerotic bone
      remodeling and the second to localized tympanosclerosis. OBJECTIVE: To describe
      the histopathologic features of malleus head fixation and to correlate them with
      its clinical appearance. MATERIAL AND METHODS: Ten patients with surgically
      proven malleus head fixation were included in this series. A fixed malleus head
      was resected via a transcanal approach in six patients, and attic bony fragments
      fixing the malleus head were removed via a mastoidectomy without disruption of
      the ossicular chain in four. Histopathologic studies were performed for both
      types of malleus head fixation. RESULTS: Three types of acquired malleus head
      fixation were defined in accordance with the surgical and histopathological
      findings. Histologically, the first type presented with normal bone tissue, the
      second was characterized by non-tympanosclerotic bone remodeling and the third
      presented with a localized tympanosclerotic focus in the tympanic cavity.

PMID- 16608786
TI  - Analysis of the vestibulo-ocular reflex time constant in patients with benign
      recurrent vertigo associated with head-shaking nystagmus.
AB  - CONCLUSIONS: When considering benign recurrent vertigo and a similar peripheral
      vestibular deficiency, the asymmetry of the vestibulo-ocular reflex (VOR) time
      constant (Tc) is lower in those patients with paretic head-shaking nystagmus
      (HSN) than in those with reversed HSN or without HSN. OBJECTIVE: To determine
      whether the existence of HSN is related to the time constant of the VOR in
      patients with benign recurrent vertigo (BRV). PATIENTS AND METHODS: This was a
      prospective study conducted at a tertiary care center in which patients were
      subjected to the head-shaking test, the caloric test and rotatory chair impulsive
      test on the same day. The clinical features of the disease analyzed were the
      disease duration, frequency of vertigo spells, time since the last vertigo spell
      and the existence of migraine. The results of the head-shaking test were
      considered positive when nystagmus appeared after head-shaking had ended. Two
      groups of patients were established on the basis of these results and the group
      that displayed HSN was divided according to the direction of nystagmus. In the
      impulsive test, the time constant of the VOR after ipsilesional and
      contralesional acceleration was analyzed, as was the symmetry of the response.
      The differences in the means were calculated. RESULTS: BRV was diagnosed in 25%
      of patients suffering recurrent spells of vertigo, of which 33 patients were HSN-
      and 29 were HSN+. In the latter group, vestibular migraine was frequently
      observed (83% of the patients), the spells of vertigo were more frequent and the
      patients were seen closer to the previous spell of vertigo. No differences were
      observed in the Tc of the VOR between HSN+ and HSN- patients, although the
      asymmetry of this Tc was higher in HSN- patients than in HSN+ patients.
      Nevertheless, the differences observed were only significant between paretic and
      reversed HSN patients and paretic HSN patients and HSN- patients.

PMID- 16608787
TI  - Recovery of vestibular evoked myogenic potentials after a vertigo attack due to
      vestibular neuritis.
AB  - CONCLUSIONS: Inferior vestibular nerve functions could recover in patients with
      vestibular neuritis (VN). OBJECTIVES: Although the recovery of superior
      vestibular nerve functions has been reported, there is little information about
      the recovery of inferior vestibular nerve functions in patients with VN. This
      study was done to clarify if inferior vestibular nerve functions recover after an
      attack of VN. METHODS: Neuro-otological tests including vestibular evoked
      myogenic potential (VEMP) testing and caloric testing were sequentially performed
      in 13 patients with VN, who showed absence of VEMP on the affected side at the
      initial examination (7 men and 6 women, 28-82 years of age). VEMPs to click
      stimulation (95 dBnHL) were recorded with surface electrodes over each
      sternocleidomastoid muscle. RESULTS: Among the 13 patients, 5 patients (4 men and
      1 woman) showed recovery of VEMP responses. Four of the five patients (three men
      and one woman) showed recovery of VEMP to the normal range. It takes 6 months to
      2 years to recover within the normal range. On the other hand, caloric responses
      recovered to the normal range only in one patient.

PMID- 16608788
TI  - Spontaneous musical auditory perceptions in patients who develop abrupt bilateral
      sensorineural hearing loss. An uninhibition syndrome?
AB  - CONCLUSIONS: Spontaneous musical auditory perceptions commonly occur in patients
      who develop abrupt bilateral sensorineural hearing loss. The findings in both
      subjects who were image tested while having these perceptions are suggestive of a
      biological substrate for this process and of a central locus for auditory memory
      seemingly located in and around area 39 of Brodmann. When an individual has
      abrupt bilateral sensorineural hearing loss, stored musical memory can be
      released and this person can have musical perceptions without an external source.
      It is likely that an abrupt bilateral loss of inner ear function might uninhibit
      neuronal groups storing auditory memory. OBJECTIVES: The objectives of this study
      were as follows. (1) To determine if spontaneous musical auditory perceptions
      occur in patients who develop abrupt bilateral severe sensorineural hearing loss
      (not necessarily simultaneously). (2) To determine if there is a biological
      substrate to the process of recalling previous auditory perceptions. (3) To
      compare these findings with our normal databases of unstimulated and pure tone
      stimulated volunteers. (4) To establish a hypothesis for the mechanisms of these
      occurrences. PATIENTS AND METHODS: Thirty two patients who had had abrupt
      bilateral severe sensorineural hearing loss (the interval between the losses of
      both ears could have been years) were contacted. They were asked if they had ever
      had the sensation of having musical auditory perceptions without external
      auditory stimuli. Two of these patients were image tested with single photon
      computerized emission tomography (neuroSPECT) while they were having these
      perceptions. RESULTS: All of the 32 subjects had musical auditory perceptions
      following their hearing loss in the second ear or when hearing loss in both ears
      occurred simultaneously. The two patients who were image tested with neuroSPECT
      had similar findings. There was a statistically significant increase in perfusion
      in area 39 of Brodmann, more intense on the right side, with increased perfusion
      also in both frontal lobes at the middle gyrus, with bilateral hypoperfusion in
      area 38 of Brodmann. These findings are similar to those observed in normal
      volunteers stimulated with pure tones.

PMID- 16608789
TI  - Topical steroids do not downregulate expression of growth-related oncogene-alpha
      in nasal polyps.
AB  - CONCLUSIONS: Topical steroids did not affect expression of growth-related
      oncogene-alpha (GRO-alpha) in nasal polyps. The results of this study suggest
      roles for steroid-resistant gene expression in the pathogenesis of nasal polyps
      and point to the need for additional pharmacological strategies. OBJECTIVE:
      Infiltration of inflammatory cells is believed to play a role in the development
      of nasal polyps. GRO-alpha is a chemokine that recruits and activates neutrophils
      and also possesses growth stimulatory and angiogenetic properties. An increased
      presence of GRO-alpha has been demonstrated in nasal polyps compared with normal
      nasal tissue. In this study we evaluate the presence and expression levels of GRO
      alpha in nasal polyps before and after glucocorticoid treatment. MATERIAL AND
      METHODS: Nasal polyps were surgically removed in patients before and 6 weeks
      after treatment with topically applied fluticasone. GRO-alpha gene expression and
      the presence of GRO-alpha peptide were detected in polyp tissue by means of in
      situ hybridization, quantitative real-time reverse transcriptase polymerase chain
      reaction and immunohistochemistry. RESULTS: Strong GRO-alpha gene expression and
      the presence of GRO-alpha peptide were seen in both the epithelium and stromal
      inflammatory cells of nasal polyps. No differences in gene expression levels in
      tissue homogenates were found when untreated polyp tissue was compared with
      polyps treated for 6 weeks with topically applied steroids.

PMID- 16608790
TI  - Preseptal transconjunctival approach for orbital floor fracture repair:
      ophthalmologic results in 209 patients.
AB  - CONCLUSIONS: The transconjunctival approach to orbital floor fractures permits
      excellent exposure of the inferior orbit and provides a good surgical outcome,
      especially with regard to ocular motility. OBJECTIVE: Surgical access to orbital
      floor fractures can be accomplished via the transconjunctival approach. The
      majority of studies on this subject deal with surgical aspects and complications.
      The purpose of this study was to report the ophthalmologic outcome after
      transconjunctival orbital floor fracture repositioning in a significant number of
      patients. MATERIAL AND METHODS: In a retrospective study, the data of 209
      patients with orbital floor fractures treated via the transconjunctival approach
      with (n=181) and without (n=28) lateral canthotomy were analyzed. RESULTS: The
      commonest cause of injury was forms of violence (32%). An isolated fracture of
      the orbital floor had occurred in 62 cases, while concomitant facial fractures
      were present in the remaining 147. A total of 24 patients (11%) had an
      exophthalmos and 13 (9%) an enophthalmos. Most patients (69%) complained of
      infraorbital dysesthesia. When elevating the eyeball, the majority of patients
      showed a marked or severe disturbance of ocular motility (53% in abduction; 51%
      in adduction) and diplopia (37% in abduction; 36% in adduction). Thirteen
      patients required repeat surgery. After a follow-up period of 2 years,
      infraorbital dysesthesia was observed in only three patients, one of whom
      presented with a considerable persistent enophthalmos of 4 mm, and only four
      patients had persistent reduced motility and diplopia.

PMID- 16608791
TI  - The effect of allergen provocation on the nasal cycle estimated by acoustic
      rhinometry.
AB  - CONCLUSION: The overall duration and reciprocity of the nasal cycle were not
      changed after allergen provocation. The duration of immediate response was 38
      min, but the amplitude of the nasal cycle was increased significantly after
      allergen provocation. OBJECTIVE: Nasal airflow is asymmetrical and subjected to
      spontaneous reciprocal changes which are referred to as the nasal cycle. Limited
      information is available on how this is affected by allergens. The purpose of
      this study was to evaluate the effects of allergen provocation on the nasal
      cycle. MATERIALS AND METHODS: This study was performed on 25 patients with
      allergic rhinitis and 25 subjects in a control group with no symptoms of allergic
      rhinitis. Acoustic rhinometry was used to test patients before and after allergen
      provocation. The patients underwent acoustic rhinometry at 15-min intervals for
      evaluation of nasal cycle and 3-min intervals for immediate response. RESULTS:
      With the allergic patients, 21 of the 25 patients (84.0%) showed a nasal cycle
      and they still had a nasal cycle after the allergen provocation. In the study on
      the changes in the immediate responses, the average recovery time was 38 min and
      the reduction rate of the non-patent side was higher than that of the patent
      side. Also, the average period of the nasal cycle was 153 min before the allergen
      provocation and 140 min on average after the allergen provocation; there were no
      statistical differences. The amplitude of each nasal cycle increased after
      allergen provocation and the difference had statistical meaning.

PMID- 16608792
TI  - Factors affecting the bacteriology of deep neck infection: a retrospective study
      of 128 patients.
AB  - CONCLUSIONS: Broad-spectrum antibiotics are advocated for treating deep neck
      infection. Anaerobic coverage is necessary, especially in odontogenic cases. The
      presence of diabetes, infection of the parotid space and an obvious odontogenic
      source of infection can aid in determining the causative organisms. OBJECTIVES:
      This study aimed to analyze the bacteriology in deep neck infections and identify
      the factors that influenced the causative pathogens. MATERIALS AND METHODS: The
      records of 212 patients who were diagnosed as having deep neck infections at the
      National Taiwan University Hospital between 1997 and 2003 were reviewed; 128
      patients with bacterial isolation from their pus cultures were enrolled. RESULTS:
      The cultures of 46 patients (35.9%) were polymicrobial. Viridans Streptococcus
      was the most commonly isolated organism (38.3%), followed by Klebsiella
      pneumoniae (32.0%) and Peptostreptococcus (17.2%). The most common organism in 44
      diabetic patients was K. pneumoniae (54.5%), versus viridans streptococcus
      (48.8%) in 84 nondiabetic patients. In patients with dental sources of
      infections, the culture rate of anaerobes was 59.3%; in upper airway infections
      and other sources of infections they were 22.7% and 21.5%, respectively (Chi(2)
      test, p = 0.0008). The differences in age, sex, and climate did not show any
      significant changes in the common causative pathogens. Common pathogens in the
      infection of parapharyngeal, submandibular, and extended spaces were the same as
      viridans streptococcus, but in the parotid space K. pneumoniae was the most
      common pathogen.

PMID- 16608793
TI  - Endoscopic resection of laryngeal and tracheal lesions using the microdebrider.
AB  - CONCLUSION: Endoscopic resection of laryngeal and tracheal lesions using the
      microdebrider is a safe, accurate and reliable method. OBJECTIVE: The
      microdebrider is an important tool for endoscopic nasal and sinus surgery and
      over the last few years a powered blade with a long shaft has been developed for
      endoscopic laryngeal and tracheal surgery. The aim of this non-randomized
      prospective study was to determine the advantages and disadvantages of the
      microdebrider for treating patients with different laryngeal and tracheal
      pathologies. MATERIAL AND METHODS: The laryngeal microdebrider was used under
      endoscopic control in 37 patients. In 29 cases a benign laryngeal lesion was
      removed endoscopically. In four patients debulking of a malignant obstructive
      endolaryngeal tumor was performed in order to avoid a tracheotomy. In four cases
      a bulky obstructing endotracheal lesion was removed. RESULTS: All laryngotracheal
      lesions could be removed, and this was facilitated by the use of angled rigid
      telescopes and the laryngeal blade. No traumatic lesions to normal laryngeal
      tissue occurred as a result of use of the microdebrider and no postoperative
      endolaryngeal bleeding was observed. The histological diagnosis of the biopsies
      taken with the microdebrider was accurate in every case. In three of the four
      cases with obstructive laryngeal malignancies, a tracheotomy was avoided until
      definitive therapy was undertaken. Normal breathing was restored in all patients
      with endotracheal lesions.

PMID- 16608794
TI  - Concurrent chemoradiotherapy with cisplatin, 5-fluorouracil, methotrexate, and
      leucovorin in patients with advanced resectable squamous cell carcinoma of the
      larynx and hypopharynx.
AB  - CONCLUSIONS: This regimen of concurrent chemoradiotherapy was safe and well
      tolerated. In terms of larynx preservation, the present regimen appears to be
      useful for patients with advanced resectable squamous cell carcinoma (SCC) of the
      larynx and hypopharynx. OBJECTIVES: To evaluate the efficacy and toxicity of
      concurrent chemoradiotherapy in patients with advanced resectable SCC of the
      larynx and hypopharynx, and to demonstrate the feasibility of larynx
      preservation. PATIENTS AND METHODS: Forty-six eligible patients were treated. The
      chemotherapy regimen consisted of a combination of four drugs: cisplatin (60
      mg/m(2), day 4), 5-fluorouracil (5-FU) (600 mg/m(2) given continuously for 120 h,
      days 1-5), methotrexate (MTX) (30 mg/m(2), day 1), and leucovorin (LV) (20
      mg/m(2), days 1-5). Two cycles of this regimen were given every 4 weeks during
      radiotherapy. Radiotherapy was delivered 5 days a week using a single daily
      fraction of 1.8-2.0 Gray, to a total dose of 66.6-70.2 Gray. RESULTS: The 3-year
      disease-specific survival rates of patients with laryngeal or hypopharyngeal SCC
      were 81.3% and 78%, respectively. The 3-year disease-specific survival rates with
      larynx preservation of patients with laryngeal or hypopharyngeal SCC were 46.7%
      and 59%, respectively. The main toxicities were neutropenia, dermatitis,
      mucositis, and infection.

PMID- 16608795
TI  - p16(INK4alpha)/exon 2 mutations in squamous cell carcinoma of the head and neck
      region.
AB  - CONCLUSIONS: In the samples of squamous cell carcinoma (SCC) of the head and neck
      region studied, mutations of exon 2 were quite rare. In contrast to the other
      three mutations, the G to C transversion on position 169 (Ala57Pro) has been
      found in several other studies before. Further investigations on mutations of the
      other exons 1alpha, 1beta and 3 are necessary. OBJECTIVE: Alterations of
      p16(INK4A) have been found in different types of human cancer cell lines. The aim
      of this study was to perform a screening for alterations of exon 2 of different
      SCCs of the head and neck region. METHODS: Forty samples of different SCCs of the
      head and neck were collected by biopsy or surgical resection. Exon 2 was
      amplified by using the primers 5'-GGTGAGGGGGCTCTACACAAG-3' and 5'
      GTCTCCCGGGCTGAACTTTC-3'. DNA was sequenced with the primer 5'
      CGGGCTGAACTTTCTGTGCT-3'. RESULTS: Mutations were found in 4 of our 40 samples.
      One sample showed a G to C transversion on position 169 (Ala57Pro), a second
      sample from the same patient confirmed the latter transition but also contained a
      transition C to T on position 179 (Ala60Val). Another patient showed an already
      known polymorphism, a transition G to A at position 442 (Ala148Thr). The third
      case was a transversion C to A on position 213 (Asn71Lys).

PMID- 16608796
TI  - Is Ki67 a marker for the transformation of laryngeal dysplasia to carcinoma?
AB  - CONCLUSION: Ki67 is not a reliable marker of malignant transformation in
      laryngeal dysplasia. OBJECTIVES: No reliable means of predicting which cases of
      laryngeal dysplasia will undergo malignant transformation currently exists. Our
      aim was to evaluate Ki67, a marker of cell proliferation, as a potential marker
      for the transformation of laryngeal dysplasia to squamous cell carcinoma.
      PATIENTS AND METHODS: Eighty consecutive cases of previously untreated patients
      with a histological diagnosis of laryngeal dysplasia from 1987 to 1993 were
      identified from the pathological archives. Standard immunohistochemical
      techniques were used to identify Ki67-positive cells and activity was scored on a
      scale of 0-4 using defined criteria. RESULTS: Of the 80 cases there were 24
      females and 56 males with a mean age of 56 years (range 29-80 years). Twenty
      cases subsequently transformed to a squamous cell carcinoma. For each Ki67 score
      (0-4), the rate of malignant transformation was: 0, 1 of 6 patients (17%); 1, 7
      of 33 patients (21%); 2, 5 of 22 patients (23%); 3, 4 of 13 patients (31%); and
      4, 3 of 6 patients (50%). A higher Ki67 score seemed to correlate with a higher
      likelihood of malignant transformation but this did not reach statistical
      significance (p=0.17, Pearson chi(2) test). Considering a score of 3 or 4 as
      positive for predicting malignant transformation produced a test of relatively
      high specificity (80%) but poor sensitivity (35%).

PMID- 16608797
TI  - Interference between muscle relaxation and facial nerve monitoring during
      parotidectomy.
AB  - CONCLUSION: There is a worst case scenario involving a small risk of facial nerve
      injury and dysfunction of facial nerve monitoring. With regard to patient safety
      the use of a short-acting muscle relaxant and the analysis of neuromuscular
      blockade are necessary because these permit documentation of the temporal course
      of relaxation and the progress of surgery. OBJECTIVES: The use of muscle relaxant
      may disturb facial nerve monitoring during parotidectomy. The aim of the study
      was to analyze the duration of muscle relaxation in relation to the progress of
      surgery. STUDY DESIGN/METHODS: Twenty-one patients who underwent parotidectomy
      were enrolled in this prospective study, where the short-acting muscle relaxant
      mivacurium (0.2 mg/kg) was used. The neuromuscular blockade was monitored on the
      basis of train-of-four (TOF) peripheral stimulation. The time of intubation, skin
      incision, facial nerve identification and the end of surgery were documented.
      RESULTS: The mean times of the TOF ratios (2/4; 3/4; 4/4), skin incision, and
      facial nerve identification differed significantly (chi(2)=0.05; df=1; p>0.05).
      For the earliest skin incision (21 min), 14.3% of patients have a TOF ratio
      smaller than 2/4 at which a neuromuscular block of the facial nerve is possible.

PMID- 16608798
TI  - A secondary middle turbinate co-existing with an accessory middle turbinate: an
      unusual combination of two anatomic variations.
AB  - The anatomy of the nasal cavity lateral wall is quite complex; this is where most
      anatomical anomalies occur. The secondary middle turbinate, a bony projection
      that arises from the lateral nasal wall, is a rare variation, differing from the
      accessory middle turbinate by its distinct developmental origin. We report on an
      unusual case involving a combination of these two turbinate variations. We
      believe that detailed knowledge of anatomical anomalies in the sinonasal tract is
      critical for successful clinical management and important in allowing the surgeon
      to perform safe functional endoscopic sinus surgery.

PMID- 16608799
TI  - Successful microsurgical primary replantation of an amputated cheek.
AB  - Standard secondary reconstruction procedures are usually applied for the
      amputation of facial soft tissue, although these procedures lead to
      unsatisfactory results: in case of an avulsed cheek, a number of important vital
      cheek functions cannot be restored. More importantly, patients with artificial
      cheeks often face considerable psychological and social difficulties. Therefore,
      it appeared to be of interest to conserve soft tissue amputated from the face and
      to perform a replantation, despite the known problem that cheek veins cannot be
      re-anastomosed, especially in avulsion injuries. Here, we report a successful
      microsurgical cheek replantation in a 55-year-old female patient, who had lost
      cheek soft tissue together with parts of her mouth.

PMID- 16608800
TI  - Malignant eccrine poroma invading the parotid gland.
AB  - Malignant eccrine poroma was first described by Pinkus and Mehregon in 1963.
      Because of the histologic characteristics of the tumor, these authors concluded
      that the tumor was likely of eccrine origin. Malignant eccrine poroma originates
      from the intraepidermal ductal portion of the eccrine gland. Like other tumors of
      skin adnexa, malignant eccrine poroma is a rare tumor. It mostly affects older
      persons. Clinical diagnosis is difficult, and lesions are often mistakenly
      identified as squamous cell carcinoma or pyogenic granuloma. We report a case of
      malignant eccrine poroma invading the parotid gland. A 65-year-old man presented
      with an ulcerated mass (2x3 cm) below the ear lobule of 3 months' duration. The
      mass was fixed to the skin and underlying parotid gland. The lesion was treated
      using a superficial parotidectomy approach including the overlying skin.
      Simultaneous neck dissection was performed. The diagnosis was malignant eccrine
      poroma invading the parotid gland.

PMID- 16608801
TI  - Application of mitomycin C after endoscopic lysis of congenital laryngeal web
      combined with epiglottic hypoplasia in a middle-aged man.
AB  - Laryngeal webs and epiglottic hypoplasias are uncommon congenital anomalies.
      Anterior glottic web combined with epiglottic hypoplasia was found in a middle
      aged man presenting with hoarseness and dyspnea on exertion. This can be
      considered as a unique isolated defect of the larynx during early fetal
      development. The laryngeal web can be successfully treated in a single stage with
      endoscopic lysis and topical application of mitomycin C for prevention of
      anterior glottic restenosis. This case and prior reports suggest that the novel
      approach may be effective in the treatment of laryngeal webs.

PMID- 16608802
TI  - Lobular capillary haemangioma of the middle turbinate.
AB  - Lobular capillary haemangioma (LCH) is a benign, vascular lesion of unknown
      origin. It usually affects skin and mucous membranes of the oral cavity. It
      rarely occurs in the nose. Microtrauma and hormonal factors are considered in the
      aetiology. The most frequently seen symptoms of nasal LCH are epistaxis and nasal
      obstruction. LCH can be pedinculated or wide based. Its size ranges from several
      millimetres to centimetres. LCH cases secondary to postoperative use of nasal
      packs have been reported. Here we present an LCH which was located on the middle
      turbinate and occurred after the usage of nasal packing. It is known that the
      nose is a rare location for LCH but middle turbinate location has not been
      described so far in the literature. LCH should be considered in the differential
      diagnosis of all endonasal masses with bleeding.

PMID- 16608803
TI  - A case of osteochondroma of the atlas causing obstructive sleep apnea syndrome.
AB  - Most osteochondromas affect the long bones, but rarely originate in the spine. We
      report an extremely rare case of osteochondroma of the atlas causing obstructive
      sleep apnea syndrome (OSAS) in a 61-year-old female. The osteochondroma was
      removed completely using a transoral approach, and the symptoms of OSAS
      disappeared. A review of the literature regarding osteochondroma confirms the
      rarity of this lesion and the use of a transoral approach is discussed.

PMID- 16608804
TI  - Iatrogenic infections in urological practice: concepts of pathogenesis,
      prevention and management.
AB  - In this paper we review the pathogenesis, prevention and management of iatrogenic
      infection in urological practice. A systematic literature search was conducted
      using MEDLINE. The topics discussed include the commonest home-care, outpatient,
      endourologic and open surgical procedures. In addition, we discuss iatrogenic
      urinary infections associated with special situations, including urinary
      diversion, urologic prostheses, diabetes mellitus, dialysis, kidney
      transplantation and complicated urinary tract infections (UTIs). The findings of
      the literature review are as follows. Prophylactic antibiotics are not
      recommended with clean intermittent catheterization. With prolonged
      catheterization, antibiotics should not be used unless symptoms of pyelonephritis
      or septicemia become apparent. With transrectal prostate biopsy, infection can be
      prevented by rectal cleansing, use of smaller needles and administration of
      antimicrobial prophylaxis before and after the procedure. With ureteral stents,
      antibiotics should be restricted to patients with clinical signs of infection and
      high-risk patients. Infections after transurethral resection of the prostate can
      be prevented by avoiding risk factors and using perioperative antibiotics. In
      endourological procedures, antibiotic prophylaxis is indicated in cases of
      infected stones, preoperative UTIs or prolonged procedures. Antibiotics are not
      recommended for clean wounds, as prophylaxis for clean-contaminated wounds or as
      therapy for contaminated and dirty wounds. In patients with urinary diversion,
      the objective is to prevent pyelonephritis by avoiding both reflux and
      obstruction of the upper urinary tract. In patients with urological prostheses,
      the most important measure to overcome iatrogenic infection is prevention. In
      dialysis patients, iatrogenic infections can be prevented by the development of
      new catheter materials that are less susceptible to biofilms. In kidney
      transplant recipients, iatrogenic infections can be prevented by treating all
      types of infection prior to transplantation and by using peri- and postoperative
      prophylactic antibiotics.

PMID- 16608805
TI  - Meta-analysis of vesicoureteral reflux and urinary tract infection in children.
AB  - OBJECTIVE: We evaluated the efficacy of medical and surgical treatment of
      vesicoureteral reflux (VUR) in children by means of a meta-analysis, using the
      recurrence of urinary tract infections (UTIs), renal growth and renal scarring as
      endpoints. MATERIAL AND METHODS: We performed a MEDLINE search for articles
      published in the English language between 1966 and 2002. Of 639 relevant articles
      found, 139 were chosen for a close review and the main database was supplemented
      with some additional articles derived from the references of these reviewed
      articles. Five studies were found acceptable for a meta-analysis. We reviewed all
      articles independently. All reviewers had to approve the accepted articles and
      data that were used in this meta-analysis. RESULTS: Operative treatment of VUR
      was better than medical treatment in terms of abolishing reflux (OR = 0.033; 95%
      CI 0.010-0.107). We found no statistically significant differences between
      surgically and medically treated patients in terms of kidney growth (OR = 2.46;
      95% CI 0.74-8.16), scarring (OR = 1.05; 95% CI 0.71-1.55) or recurrence of UTIs
      (OR = 0.80; 95% CI 0.49-1.29). We could not evaluate possible differences in the
      parameters monitored between boys and girls because of a lack of data.
      CONCLUSIONS: Although surgical treatment of VUR is a common pediatric urologic
      procedure, the data relating to it are scanty. We found no clinically significant
      differences between surgical and medical treatment for VUR other than in the
      resolution of VUR itself. On the basis of present evidence we suggest that a
      child with UTI and significant VUR should be treated conservatively at first and
      that surgical treatment should be reserved for children who experience problems
      with antimicrobials or persistent clinically significant VUR after several years
      of follow-up.

PMID- 16608806
TI  - Postoperative urinary continence after robot-assisted laparoscopic radical
      prostatectomy.
AB  - OBJECTIVE: Laparoscopic radical prostatectomy has shown excellent results
      concerning patient morbidity, with less blood loss compared to conventional
      surgery. Robot-assisted laparoscopy offers several additional important technical
      improvements and therefore it might be suggested that robotic radical
      prostatectomy would also offer surgical advantages. The objective of this study
      was to evaluate urinary continence for the first 72 cases of robot-assisted
      radical prostatectomy performed by a single surgical team. MATERIAL AND METHODS:
      We analysed the outcomes of the first 72 consecutive patients to undergo robot
      assisted prostatectomy for localized prostate cancer at our hospital between
      January 2002 and May 2004. A self-administered questionnaire concerning urinary
      status was mailed to the patients 3 and 6 months after surgery. Pre- and
      peroperative characteristics were obtained from patient medical records. The mean
      age was 61.2 years (range 36-71 years) and the mean preoperative prostate
      specific antigen level was 6.3 ng/ml (range 2.3-10.7 ng/ml). The preoperative
      clinical stage was T1c, 67%, T2, 28% and T3, 5% and the mean Gleason sum was 6
      (range 5-9). RESULTS: Sixty-one of the 68 patients (90%) reported no use of pads
      and 6 (9%) used a maximum of 1 pad/day 3-6 months after surgery. One patient
      reported use of >1 pad/day 6 months after surgery. Three significant
      complications were noted: ureter injury, haemorrhage and femoral nerve injury.
      CONCLUSIONS: In this series, which represents the learning curve for one surgical
      team, only a tenth of the patients still required pads 3-6 months after surgery.
      Considering the short follow-up period, the results in this series will probably
      improve over time.

PMID- 16608807
TI  - Comparative study of zinc levels in benign and malignant lesions of the prostate.
AB  - OBJECTIVES: The normal human prostate accumulates the highest levels of zinc of
      any soft tissue in the body. The presence of zinc in the prostate of a number of
      mammalian species, including rhesus monkeys and humans, has been well documented.
      The aims of this study were to investigate the concentrations of zinc in various
      disorders of the prostate and to find a correlation between them. MATERIAL AND
      METHODS: A total of 80 cases were studied (20 normal, 50 benign, 10
      carcinomatous). A plasma sample was taken and zinc levels were analyzed using
      atomic absorption spectrophotometry. RESULTS: The mean (+/-SD) plasma zinc level
      in the normal cases was 94.5+/-10.38 microg/100 ml. Amongst patients with benign
      diseases of the prostate gland, the plasma zinc level was 145.4+/-9.67, 162.4+/
      2.22 and 172.7+/-5.27 microg/100 ml (78% rise compared to normal patients) in
      those with a fibromuscular prostate, chronic prostatitis and benign prostatic
      hyperplasia, respectively, whilst patients with malignancy had a plasma zinc
      level of 59.6+/-3.08 microg/100 ml (37% fall compared to normal patients). There
      was a highly statistically significant (p < 0.01) difference in plasma zinc
      levels between patients with benign and malignant prostate diseases. The effect
      of metastasis of carcinoma of the prostate on plasma zinc levels was not
      significant (p > 0.05), while there was a highly statistically significant (p <
      0.01) correlation between serum prostate-specific antigen and plasma zinc levels
      in malignancy. CONCLUSIONS: There appears to be a strong correlation between
      plasma zinc levels and various prostatic diseases. Therefore, the determination
      of zinc levels can be used as a diagnostic or screening tool and may lead to the
      formulation of methods in which zinc is used to evaluate prostatic pathology.

PMID- 16608808
TI  - Extracorporeal shock-wave lithotripsy or ureteroscopy as primary treatment for
      ureteric stones: a retrospective study comparing two different treatment
      strategies.
AB  - OBJECTIVE: Our extracorporeal shock-wave lithotripsy (ESWL) lithotripter with
      ultrasound localization technique was replaced in 1999 by a Storz SLX-MX
      lithotripter with both X-ray and ultrasound detection possibilities. Before
      replacing our lithotripter, most ureteric stones were treated with ureteroscopy
      (URS); subsequently, almost all patients underwent ESWL as primary treatment. The
      aim of this retrospective study was to compare the results of these two treatment
      strategies in all consecutive patients attending our hospital in 1998 and 2000
      for ureteric stone treatment. MATERIAL AND METHODS: The medical records of all
      patients treated for ureteric stones in 1998 and 2000 were reviewed. In 1998, 173
      ureteric stones were treated. Primary treatment was URS in 124 patients, push
      back/ESWL in 24, ESWL in 21 and open surgery in four. In 2000, 176 ureteric
      stones were treated: 158 with ESWL and 18 with URS. ESWL or URS monotherapy was
      defined as ESWL or URS, respectively as the only stone-treatment therapy, with or
      without the use of a ureteric catheter or nephrostomy tube. Treatment success was
      defined as a stone-free ureter. RESULTS: In 1998, the success rate for URS
      monotherapy was 95%, with a retreatment rate (sessions per stone situation) of
      1.06. Corresponding figures for ESWL monotherapy in 2000 were 90% and 1.69. All
      URS patients received general anaesthesia; ESWL patients received opiods.
      Complication rates were 6% for URS and 3% for ESWL. In the URS group, 4/8
      complications were considered to be major. CONCLUSION: ESWL should be considered
      the first-line treatment for ureteric stones because of its non-invasive nature,
      lack of a requirement for general anaesthesia and low complication rates.

PMID- 16608809
TI  - Immediate versus deferred radiological investigation after acute renal colic: a
      prospective randomized study.
AB  - OBJECTIVE: The timing of radiological assessment after acute renal colic is
      controversial. The aim of this study was to investigate the value of immediate
      versus deferred radiological imaging and to compare morbidity rates after an
      attack of acute renal colic. MATERIAL AND METHODS: Between September 2001 and
      December 2002 all 686 patients with acute renal colic attending our university
      hospital were registered. Of these, 172 patients rendered pain-free after
      analgesic injection were randomized to either immediate or deferred radiological
      investigation. All patients received a questionnaire encompassing questions on
      consumption of analgesics, impact of symptoms on normal daily activity (including
      working ability), need for additional emergency department visits and
      hospitalization. Stone treatments were registered. RESULTS: The incidence of
      renal colic was 0.9/1,000 inhabitants per year. In total, 74% of all patients
      became pain-free after analgesic injection. Morbidity was low among the
      randomized patients, and did not differ between the immediate or deferred
      radiological investigation groups. In both groups, the duration of impairment of
      normal daily activities and analgesic consumption was a median of 2 days. In the
      immediate group, 14% needed another emergency visit and 4% were hospitalized.
      Corresponding figures for the deferred group were 15% and 7%. In the immediate
      group, 17% had stone treatment, compared with 8% in the deferred group.
      CONCLUSION: For most patients with acute renal colic, parenteral analgesia
      resulted in complete symptom resolution. When initial medical treatment was
      successful, patient morbidity was low. In these patients, immediate radiological
      imaging did not lead to reduced morbidity compared with radiological imaging
      after 2-3 weeks.

PMID- 16608810
TI  - Measurement of nitric oxide may differentiate between inflammatory and non
      inflammatory prostatitis.
AB  - OBJECTIVE: The majority of patients with prostatitis have chronic non-bacterial
      prostatitis/chronic pelvic pain syndrome of inflammatory type (Category IIIA) or
      non-inflammatory type (Category IIIB), based on the National Institutes of Health
      classification. The aim of this study was to investigate whether measurement of
      nitric oxide (NO) formation in the prostatic urethra can be used as a marker for
      inflammation in the evaluation of patients with chronic prostatitis/pelvic pain
      syndrome. MATERIAL AND METHODS: A total of 25 men with prostatitis were examined.
      In 8 patients >10 white blood cells/high-power field (WBC/hpf) were found in
      expressed prostatic secretion (EPS) (Category IIIA), whereas the other 17 had no
      signs of inflammation (Category IIIB). NO production was measured using a silicon
      catheter, with the catheter balloon being placed in the prostatic urethra. Room
      air (5 ml) was incubated for 5 min and analyzed. NO formation in the urinary
      bladder was also measured. RESULTS: The NO concentration in the prostatic urethra
      was significantly higher in the 8 patients with >10 WBC/hpf than in those with
      <10 WBC/hpf. The NO concentration in the urinary bladder was low in both groups.
      CONCLUSIONS: We found an elevated NO concentration in the prostatic urethra in
      patients with >10 WBC/hpf in the EPS but not in those with <10 WBC/hpf, which
      supports the theory of different pathogeneses for Categories IIIA and IIIB.
      Measurement of NO production in the prostatic urethra can be used to discriminate
      between the two categories and as the method is easy and fast it may represent an
      attractive alternative to the four-glass test.

PMID- 16608811
TI  - Quality of life after tension-free vaginal tape surgery for female stress
      incontinence.
AB  - OBJECTIVE: To undertake a long-term follow-up evaluation of the quality of life
      (QOL) of women who had undergone a tension-free vaginal tape (TVT) procedure.
      MATERIAL AND METHODS: During the period 1995-2001, 970 women with urinary stress
      incontinence underwent TVT surgery at the Department of Obstetrics and
      Gynecology, Falun Hospital. A questionnaire was mailed on average 5.7 years after
      the TVT procedure. Two incontinence-specific QOL instruments--the Incontinence
      Impact Questionnaire-7 (IIQ-7) and the Urogenital Distress Inventory-6 (UDI-6)-
      were administered. An additional questionnaire included general questions and
      questions about chronic diseases that may be associated with urinary
      incontinence. RESULTS: The mean age at surgery was 58.7 years (range 29-89
      years). Of 913 eligible women, 768 (78.9%) responded. Mean IIQ-7 and IDU-6 scores
      as estimated by the women improved dramatically at follow-up as compared to
      preoperative values: from 43.7 to 11.5 for the IIQ-7 and from 54.2 to 24.0 for
      the UDI-6 on a scale from 0 to 100 (p = 0.0001 for both). There were few
      differences in mean QOL scores even 8 years after TVT surgery, compared to those
      determined a shorter time after the operation. Women with diabetes, chronic
      constipation, chronic bronchitis and preoperative recurrent urinary infections
      had a relative improvement in QOL of the same magnitude as that of the remaining
      study population. Advanced age was negatively associated with an improvement in
      QOL scores. CONCLUSIONS: Improvements in measures of QOL after TVT surgery are
      dramatic and persist for years. Women with concomitant diseases that may be
      associated with urinary incontinence can be assured that there is a good chance
      of success with TVT surgery.

PMID- 16608812
TI  - Prevalence of genital human papillomavirus infections established using different
      diagnostic techniques among males attending a urological clinic.
AB  - OBJECTIVE: To compare the accuracy of different diagnostic methods and their use
      in estimating the prevalence of genital human papillomavirus (HPV) infections in
      males attending a urological clinic. MATERIAL AND METHODS: The study population
      was derived from a series of 1,153 consecutive males attending a urological
      clinic in Sao Paulo between January 1996 and November 1998. Of these 1,153 males,
      334 had clinically suspected genital HPV infection and comprised the study
      cohort. The diagnostic methods used included peniscopy, directed biopsy and HPV
      detection by means of the Hybrid Capture 2 (HC) assay for both oncogenic and non
      oncogenic HPV types. RESULTS: Peniscopy was performed for 297 males, positive
      results being reported in 237 cases (79.8%). Directed biopsy was performed in 188
      males, and histology suggested HPV in 140 of these cases (74.5%). HC confirmed
      the presence of HPV in only 35.2% of the histologically HPV-suggestive cases.
      Peniscopy has good sensitivity for identifying male carriers of genital HPV.
      However, the technique has an inherent low specificity, limiting its usefulness
      to the correct identification of those who never present with HPV infection.
      Characteristic histological alterations are useful in suggesting HPV infection,
      but their correlation with HPV detection using HC is not particularly good.
      CONCLUSIONS: These data suggest that both histology and peniscopy have low
      specificity in detecting male genital HPV. Accurate diagnosis of HPV infection
      can be confirmed by molecular detection methods only. Histology, however, plays
      an important role in the differential diagnosis. An appropriate diagnostic
      protocol for male genital HPV infections in a urological clinic should include
      peniscopy, histology and molecular diagnostic tools (HC or polymerase chain
      reaction).

PMID- 16608813
TI  - Vascular endothelial growth factor in serum indicates cardiovascular risk in
      urology patients.
AB  - OBJECTIVE: We hypothesized that a high serum concentration of vascular
      endothelial growth factor (VEGF), a cytokine involved in prostate growth which is
      also upregulated in chronic ischemia, indicates an increased risk of
      cardiovascular disease and death in urology patients. MATERIAL AND METHODS: The
      serum VEGF concentration was measured in 219 males (mean age 72 years) who sought
      medical attention because of lower urinary tract symptoms. Data on cardiovascular
      events and survival were obtained from the hospital registry of Stockholm County
      and the Death Registry over a period of up to 10 years (mean 6.2 years). RESULTS:
      After adjusting for the effects of age and smoking, patients with a serum VEGF
      level in the upper 20% of the cohort (>500 pg/ml) had an increased risk of
      developing cardiovascular disease (hazard ratio 2.18; 95% CI 1.04-4.60),
      including acute myocardial infarction (3.36; 1.35-8.41) and stroke (3.98; 1.61
      9.86). They also had an increased risk of death (1.74; 1.01-3.00). These
      differences from patients with a lower serum VEGF concentration (<300 pg/ml) were
      manifested 2-5 years after the blood sample was taken. CONCLUSION: An elevated
      VEGF level in peripheral blood was a risk factor for subsequent development of
      cardiovascular disease.

PMID- 16608814
TI  - A simple device (Hemostick) for the standardized description of macroscopic
      haematuria: our initial experience.
AB  - OBJECTIVE: To evaluate the clinical use of a simple device (Hemostick) developed
      to enable a standardized description of the degree of macroscopic haematuria.
      MATERIAL AND METHODS: The visual scale (Hemostick) used in this study comprised
      six colour fields, one yellow (blank; 0) and five with different nuances of red
      (1-5) selected from a colour scale according to clinical observations of samples
      obtained from patients with macroscopic haematuria. Urine samples containing
      blood were examined and given a Hemostick score (HS) of 0-5, based on comparison
      with the colour fields on the scale. In three experimental series, (A) 63, (B +
      C) 14 and (D) 60 x 4 urine samples were examined by observers. The reported HS
      was compared with the personal descriptions of the degree of haematuria. We also
      assessed the absorbance at 412 nm, the haemoglobin concentration and the number
      of erythrocytes. RESULTS: In the first two series (A and B + C) comprising 325
      observations on 77 urine samples, the HS for the same sample as reported by the
      observers was in agreement in 75-93% of cases. In Series B + C the coefficient of
      variation was 0.06 and the mode 2.68, which was almost identical to the observed
      mean HS value of 2.69. Based on observations on 240 urine samples considered by
      four observers during four consecutive days (Series D), an acceptable agreement
      was recorded in 74-94% of cases. In this experiment the mean HS differed from the
      mode by not more than 0.12-0.19. In terms of absorbance there was very good
      discrimination between samples with HSs 1, 2, 3 and 4. Measurements of the
      haemoglobin concentration (g/l) gave us the following approximate ranges for HSs
      0, 1, 2, 3 and 4: <0.2, 0.2-1, 1-5, 5-25 and >25, respectively. Samples with HS 5
      comprised those with a high concentration of old blood. CONCLUSIONS: The results
      of this series of experiments involving scoring of macroscopic haematuria were
      encouraging. The Hemostick device was easy to use and resulted in a satisfactory
      consensus regarding the degree of haematuria and one that was superior to that
      deduced from a personal terminology.

PMID- 16608815
TI  - Relation between acute urinary retention, chronic prostatic inflammation and
      accompanying elevated prostate-specific antigen.
AB  - OBJECTIVE: To determine if there is a relationship between acute urinary
      retention (AUR), the prostate-specific antigen (PSA) level and chronic
      inflammation of the prostate. We therefore studied patients with benign prostatic
      obstruction (BPO) with (n = 64) or without (n = 168) acute urinary retention
      (AUR) who underwent transurethral resection of the prostate (TURP) in a
      retrospective case control study. MATERIAL AND METHODS: Between 2001 and 2004, a
      total of 232 patients underwent TURP due to BPO with or without AUR. The mean
      values of age, prostate volume, weight of resected prostate and PSA level and the
      histopathologic results of patients with and without AUR were compared. Chi(2)
      analysis was used to examine the relationship between prostatic inflammation and
      AUR. The contribution of each variable to AUR was assessed by means of multiple
      linear regression. RESULTS: A total of 64 patients (28%) were operated on for AUR
      due to BPO. There were no statistical differences between patients with or
      without AUR with respect to the mean values of PSA, percent free PSA, prostate
      size or weight of the resected prostate tissue. Elevated PSA values (>or=4.0
      ng/ml) were detected in 64% and 38% of the patients in the AUR and non-AUR
      groups, respectively (p = 0.01). Histopathological re-evaluation demonstrated
      that chronic prostatic inflammation was present in 56% and 37% of the specimens
      in the AUR and non-AUR groups, respectively (p = 0.014). In the AUR group, the
      mean PSA level was significantly higher in patients with than without prostatic
      inflammation (7.75+/-5.26 vs 5.07+/-3.21 ng/ml; p = 0.022). The odds ratio of AUR
      for patients with chronic prostatic inflammation and elevated PSA was determined
      as 4.14 (95% CI 1.65-10.41). Multiple linear regression revealed that prostatic
      inflammation made a significant contribution to AUR. CONCLUSIONS: Chronic
      prostatic inflammation may be histopathological evidence of both elevated PSA
      level and AUR; hence it may play a role in the pathophysiology of AUR.

PMID- 16608816
TI  - Postoperative thrombocytosis as a marker for complications after urologic
      surgery.
AB  - OBJECTIVE: To determine whether thrombocytosis after urologic surgery is a random
      phenomenon or if it is related to postoperative complications. MATERIAL AND
      METHODS: We evaluated the postoperative course of patients who had a normal
      platelet count before surgery and developed significant thrombocytosis (platelet
      count> 500 x 10(9)/l) after surgery during the years 1991-2003. The rate of
      postoperative complications was compared among patients who did and did not
      develop thrombocytosis for the three commonest surgical procedures associated
      with the condition (radical cystectomy, percutaneous nephrolithotripsy and
      nephrectomy). RESULTS: A total of 179 patients developed thrombocytosis (mean+/
      SD platelet count 580+/-105 x 10(9)/l; range 501-1,390 x 10(9)/l) after a mean of
      13.6 days (SD 14.7 days) following surgery. In 90% of these patients,
      postoperative complications were diagnosed. The most frequent complications were
      as follows: urosepsis, n = 49 (27%); hemorrhage, n = 37 (21%); and
      thromboembolism, n = 15 (8.4%). These complications were diagnosed by means of
      clinical examination in 114 cases (64%), CT in 31 (17%), Doppler ultrasound in
      seven (4%) and other diagnostic modalities in nine. In 18 patients (10%), no
      apparent complication was diagnosed. The rate of postoperative complications was
      significantly higher among patients who developed thrombocytosis after surgery
      compared to those who did not (p < 0.00001). In 63 patients (35%), the finding of
      thrombocytosis preceded the diagnosis of the complication (by a median period of
      5 days). In these patients, thrombocytosis was essentially an early marker for
      the impending complication. CONCLUSIONS: Postoperative thrombocytosis is not a
      random phenomenon. It is a serious sign that should not be ignored. Septic and
      thromboembolic complications should be actively sought by means of thorough
      clinical evaluation. CT of the abdomen should be considered in appropriate
      clinical settings. The timing of thrombocytosis and the pathologic spectrum of
      diseases demonstrated by patients with it justify classifying it as a marker of
      the subacute phase.

PMID- 16608817
TI  - Schwannoma of the penis: a common tumour at a rare site.
AB  - Schwannoma is a benign tumour arising from neurilemmal cells and is commonly seen
      along cranial nerves. We describe the case history and histologic findings of a
      young adult with a schwannoma at a very rare site: the penis. Surgical excision
      was done and the patient remains disease-free after 2 years.

PMID- 16608818
TI  - Muscle fibrillation as a sign of electrode damage in sacral neuromodulation.
AB  - Sacral root neuromodulation is recognized as an effective therapy for chronic
      voiding dysfunction. However, knowledge about the neuromodulator in the general
      medical community is scarce. We report a case of muscle fibrillation caused by
      current leaking from a neuromodulator lead which had been damaged during disc
      prolapse surgery.

PMID- 16608819
TI  - Ventricular rupture secondary to cardiac metastasis of transitional cell
      carcinoma of the bladder.
AB  - We report a patient with transitional cell carcinoma of the bladder who had
      metastatic nodules in the myocardium of the left ventricle and tumour emboli in
      the left circumflex artery which caused myocardial infarction with ventricular
      rupture and haemopericardium. Cardiac metastasis of transitional cell carcinoma
      of the bladder is discussed and the literature reviewed.

PMID- 16608820
TI  - Urothelial carcinoma of the ureter, giant rectal stone and sigmoid carcinoma 55
      years after ureterosigmoidostomy.
AB  - We present the case of a unique accumulation of complications 55 years after
      ureterosigmoidostomy for bladder exstrophy and discuss possible implications for
      follow-up strategies.

PMID- 16608821
TI  - Nuclear aggregates of polyamines.
AB  - Nuclear aggregates of polyamines (NAPs) are cyclic supramolecular compounds made
      of polyamines and phosphate groups. Three different aggregates, s-NAP, m-NAP and
      l-NAP, with a molecular weight of 1035, 5175 and 9552 Da, respectively, are
      described. These molecules interact with genomic DNA. In consequence of this
      interaction, NAPs not only protect DNA from nucleases with extraordinarily
      greater efficiency than single polyamines (spermine, spermidine and putrescine),
      but also induce noticeable changes in DNA condensation status, as shown by
      temperature-dependent modifications of DNA electrophoretic properties. The
      biochemical characterization of these compounds has allowed the definition of a
      structural model for each NAP. According to this model, five s-NAPs assemble
      together to form a m-NAP unit. We hypothesize that the complexation of s-NAP into
      m-NAP favours the transition to Z-DNA through the progressive widening of DNA
      strands and the exposure of bases. We propose that NAPs, by wrapping the DNA
      helixes, form supramolecular tunnel-like structures that confer efficient
      protection without affecting DNA elasticity.

PMID- 16608822
TI  - Evidence against the overexpression of APP in Down syndrome.
AB  - Down syndrome (DS) is the most common genetic disorder with mental retardation
      and is caused by trisomy 21. By the age of 40 years, virtually all adults with DS
      have sufficient neuropathology for a diagnosis of Alzheimer's disease (AD), which
      is characterized by accumulation of amyloid-beta in senile plaques and formation
      of neurofibrillary tangles. Amyloid-beta derives from a longer precursor protein,
      APP, whose gene maps to chromosome 21. In DS, the early appearance of senile
      plaques is commonly associated with the presence of a third copy of the APP gene.
      Here we show DS brains and trisomic fibroblasts in which APP is not
      overexpressed, compared to euploid controls, challenging the notion that the
      widespread amyloid-beta deposits, consistently found in DS individuals, result
      from an extra copy of APP.

PMID- 16608823
TI  - According to current textbooks, a well-defined three-dimensional structure is a
      prerequisite for the function of a protein. Is this correct?

PMID- 16608824
TI  - How I became a biochemist.

PMID- 16608827
TI  - Residential radon and lung cancer: end of the story?
AB  - The earliest evidence of increased lung cancer risk associated with radon came
      largely from studies of highly exposed underground miners. In the United States,
      concerns about residential exposures became prominent in the early 1980s with the
      identification of the Watras home, which had remarkably elevated radon
      concentrations. By then, the problem of indoor radon was already recognized in
      Europe and the first epidemiological studies on indoor radon had been reported.
      The concern about the risk of indoor radon motivated a series of case-control
      studies of residential radon and lung cancer in the United States, Canada, China,
      and a number of European countries. In 1999, the U.S. National Research Council
      Committee on the Biological Effects of Ionizing Radiation (BEIR VI) weighed the
      scientific evidence available at that time on this issue and concluded that
      residential radon was an important contributor to the lung cancer burden and that
      risks were appropriately estimated by a linear nonthreshold model. Since
      individual case-control studies have not provided consistent direct evidence of
      excess lung cancer risk at residential exposure levels, combined analyses of
      residential radon studies have been undertaken in both North America and Europe.
      These combined analyses, including the North American pooled analysis described
      in this issue, represent an important complement to the findings of the miner
      studies and further support the linear no-threshold model for cancer risk adopted
      by the BEIR VI Committee and other groups.

PMID- 16608828
TI  - A combined analysis of North American case-control studies of residential radon
      and lung cancer.
AB  - Cohort studies have consistently shown underground miners exposed to high levels
      of radon to be at excess risk of lung cancer, and extrapolations based on those
      results indicate that residential radon may be responsible for nearly 10-15% of
      all lung cancer deaths per year in the United States. However, case-control
      studies of residential radon and lung cancer have provided ambiguous evidence of
      radon lung cancer risks. Regardless, alpha-particle emissions from the short
      lived radioactive radon decay products can damage cellular DNA. The possibility
      that a demonstrated lung carcinogen may be present in large numbers of homes
      raises a serious public health concern. Thus, a systematic analysis of pooled
      data from all North American residential radon studies was undertaken to provide
      a more direct characterization of the public health risk posed by prolonged radon
      exposure. To evaluate the risk associated with prolonged residential radon
      exposure, a combined analysis of the primary data from seven large scale case
      control studies of residential radon and lung cancer risk was conducted. The
      combined data set included a total of 4081 cases and 5281 controls, representing
      the largest aggregation of data on residential radon and lung cancer conducted to
      date. Residential radon concentrations were determined primarily by a-track
      detectors placed in the living areas of homes of the study subjects in order to
      obtain an integrated 1-yr average radon concentration in indoor air. Conditional
      likelihood regression was used to estimate the excess risk of lung cancer due to
      residential radon exposure, with adjustment for attained age, sex, study, smoking
      factors, residential mobility, and completeness of radon measurements. Although
      the main analyses were based on the combined data set as a whole, we also
      considered subsets of the data considered to have more accurate radon dosimetry.
      This included a subset of the data involving 3662 cases and 4966 controls with a
      track radon measurements within the exposure time window (ETW) 5-30 yr prior to
      the index date considered previously by Krewski et al. (2005). Additional
      restrictions focused on subjects for which a greater proportion of the ETW was
      covered by measured rather than imputed radon concentrations, and on subjects who
      occupied at most two residences. The estimated odds ratio (OR) of lung cancer
      generally increased with radon concentration. The OR trend was consistent with
      linearity (p = .10), and the excess OR (EOR) was 0.10 per Bq/m3 with 95%
      confidence limits (-0.01, 0.26). For the subset of the data considered previously
      by Krewski et al. (2005), the EOR was 0.11 (0.00, 0.28). Further limiting
      subjects based on our criteria (residential stability and completeness of radon
      monitoring) expected to improve radon dosimetry led to increased estimates of the
      EOR. For example, for subjects who had resided in only one or two houses in the 5
      30 ETW and who had a-track radon measurements for at least 20 yr of this 25-yr
      period, the EOR was 0.18 (0.02, 0.43) per 100 Bq/m3. Both estimates are
      compatible with the EOR of 0.12 (0.02, 0.25) per 100 Bq/m3 predicted by downward
      extrapolation of the miner data. Collectively, these results provide direct
      evidence of an association between residential radon and lung cancer risk, a
      finding predicted by extrapolation of results from occupational studies of radon
      exposed underground miners.

PMID- 16608829
TI  - An overview of the North American residential radon and lung cancer case-control
      studies.
AB  - Lung cancer has held the distinction as the most common cancer type worldwide
      since 1985 (Parkin et al., 1993). Recent estimates suggest that lung cancer
      accounted for 1.2 million deaths worldwide in 2002, which represents 17.6% of the
      global cancer deaths (Parkin et al., 2005). During 2002, the highest lung cancer
      rates for men worldwide reportedly occurred in North America and Eastern Europe,
      whereas the highest rates in females occurred in North America and Northern
      Europe (Parkin et al., 2005). While tobacco smoking is the leading risk factor
      for lung cancer, because of the magnitude of lung cancer mortality, even
      secondary causes of lung cancer present a major public health concern (Field,
      2001). Extrapolations from epidemiologic studies of radon-exposed miners project
      that approximately 18,600 lung cancer deaths per year (range 3000 to 41,000) in
      the United States alone are attributable to residential radon progeny exposure
      (National Research Council, 1999). Because of differences between the mines and
      the home environment, as well as differences (such as breathing rates) between
      miners and the general public, there was a need to directly evaluate effects of
      radon in homes. Seven major residential case-control radon studies have been
      conducted in North America to directly examine the association between prolonged
      radon progeny (radon) exposure and lung cancer. Six of the studies were performed
      in the United States including studies in New Jersey, Missouri (two studies),
      Iowa, and the combined states study (Connecticut, Utah, and southern Idaho). The
      seventh study was performed in Winnipeg, Manitoba, Canada. The residential case
      control studies performed in the United States were previously reviewed elsewhere
      (Field, 2001). The goal of this review is to provide additional details regarding
      the methodologies and findings for the individual studies. Radon concentration
      units presented in this review adhere to the types (pCi/L or Bq/m3) presented in
      the individual studies. One picocurie per liter is equivalent to 37 Bq/m3.
      Because the Iowa study calculated actual measures of exposure (concentration x
      time), its exposures estimates are presented in the form WLM(5-19) (Field et al.,
      2000a). WLM(5-19) represents the working level months for exposures that occurred
      5-19 yr prior to diagnosis for cases or time of interview for control. Eleven
      WLM(5-19) is approximately equivalent to an average residential radon exposure of
      4 pCi/L for 15 yr, assuming a 70% home occupancy.

PMID- 16608830
TI  - Indoor radon and lung cancer risk in connecticut and utah.
AB  - Radon is a well-established cause of lung cancer in miners. Residents of homes
      with high levels of radon are potentially also at risk. Although most individual
      studies of indoor radon have failed to demonstrate significant risks, results
      have generally been consistent with estimates from studies of miners. We studied
      1474 incident lung cancer cases aged 40-79 yr in Connecticut, Utah, and southern
      Idaho. Population controls (n = 1811) were identified by random telephone
      screening and from lists of Medicare recipients, and were selected to be similar
      to cases on age, gender, and smoking 10 yr before diagnosis/interview using
      randomized recruitment. Complete residential histories and information on known
      lung cancer risk factors were obtained by in-person and telephone interviews.
      Radon was measured on multiple levels of past and current homes using 12-mo alpha
      track etch detectors. Missing data were imputed using mean radon concentrations
      for informative subgroups of controls. Average radon exposures were lower than
      anticipated, with median values of 23 Bq/m3 in Connecticut and 45 Bq/m3 in
      Utah/southern Idaho. Overall, there was little association between time-weighted
      average radon exposures 5 to 25 yr prior to diagnosis/interview and lung cancer
      risk. The excess relative risk (ERR) associated with a 100-Bq/m3 increase in
      radon level was 0.002 (95% CI -0.21, 0.21) in the overall population, 0.134 (95%
      CI -0.23, 0.50) in Connecticut, and -0.112 (95% CI -0.34, 0.11) in Utah/Idaho.
      ERRs were higher for some subgroups less prone to misclassification, but there
      was no group with a statistically significant linear increase in risk. While
      results were consistent with the estimates from studies of miners, this study
      provides no evidence of an increased risk for lung cancer at the exposure levels
      observed.

PMID- 16608831
TI  - Dosimetric challenges for residential radon epidemiology.
AB  - Radon concentration alone may not be an adequate surrogate to measure for lung
      cancer risk in all residential radon epidemiologic lung cancer studies. The dose
      delivered to the lungs per unit radon exposure can vary significantly with
      exposure conditions. These dose-effectiveness variations can be comparable to
      spatial and temporal factor variations in many situations. New technologies that
      use surface-deposited and implanted radon progeny activities make more accurate
      dose estimates available for future epidemiologic studies.

PMID- 16608832
TI  - Uncertainty analysis of relative biological effectiveness of alpha-radiation for
      human lung exposure.
AB  - Assessment of relative biological effectiveness (RBE) for a radiation in the
      cases of inhalation of radon progeny and incorporation of plutonium in lung is
      based on simulation of lung cancer radiation risk for alpha and external
      reference types of radiation. Specific radiation risk models developed on the
      results of direct epidemiological studies are used for simulation. These include
      published risk models for nuclear workers of the Mayak facilities in the former
      Soviet Union exposed to incorporated plutonium (Kreisheimer et al., 2003; Gilbert
      et al., 2004) and underground miners exposed to radon progenies (BEIR VI, 1999).
      Additionally, a lung cancer risk model is developed for a case of population
      indoor radon exposure. Lung cancer risk related to external exposure is estimated
      using the risk model developed for the analyses of Japanese atomic bomb survivors
      (Preston et al., 2003). Uncertainties of risk models parameters are considered
      and the uncertainties of RBE are estimated using the results of lifetime lung
      cancer risk simulation, which is done implementing a Monte Carlo approach.
      Estimated median value of RBE in case of indoor radon exposure is 1.5 with 90%
      range 0.4-7. In the case of the two models developed by BEIR VI for lung cancer
      risk due to radon exposure in underground miners, the median values of RBE are
      2.1 and 4.4 with 90% ranges 0.3-17 and 0.7-45, respectively. The two different
      models for lung cancer risk related to plutonium exposure resulted in close
      estimates of RBE: median value of 12 and 13 with 90% range 4-104 and 4-136,
      respectively.

PMID- 16608833
TI  - Radon epidemiology: continuous and categorical trend estimators when the exposure
      distribution is skewed and outliers may be present.
AB  - As other epidemiological exposure variables, indoor radon levels have a right
      skewed, approximately lognormal distribution. The continuous linear trend
      estimator is then known to be sensitive to outlying observations. We consider
      trend estimators based on replacing the exposure x by a transformed variable z:
      (1) trimmed estimators, that is, extreme values are deleted in z; (2) winsorized
      estimators, that is, extreme values are replaced by a lower value; (3)
      categorical estimators, that is, x is categorized and the continuous variable z
      takes on scores such as the mean or median within categories. The latter approach
      is often used in meta-analyses of published odds ratios. Statistically optimal
      categories can be defined. The corresponding scores are the expected values
      within the categories, based on the assumption of a lognormal distribution. In a
      simulation study, it turned out that procedures with different cutpoints for
      cases and controls, winsorized estimators, and categorical estimators based on
      category medians can be badly biased upward. Categorical estimators using
      category means are not always robust against outlying observations. However,
      categorical estimators employing optimal categories with expected values are
      nearly unbiased, even in the presence of outliers. Cutpoints should be determined
      according to the overall distribution of cases and controls combined. Trimmed
      estimators based on this distribution are unbiased, but highly variable. For
      right-skewed exposure variables, we therefore suggest sensitivity analyses based
      on the categorical estimator with optimal cutpoints and expected value scores. In
      the West German case-control study on indoor radon and lung cancer, these
      sensitivity analyses lead to increased risk estimates.

PMID- 16608834
TI  - Impact of measurement error in exposures in german radon studies.
AB  - Case-control studies on lung cancer and residential radon exposure were conducted
      in West and East Germany. Odds ratio (OR) estimates from primary analysis are now
      subject to correction for measurement error in exposure. We apply the regression
      calibration method adopting a bivariate multiplicative error model of the
      classical type; that is, we investigate the impact of errors in the exposure of
      primary interest, radon, and of errors in the most potent confounder, smoking.
      The OR estimates per 100 Bq/m3 are throughout higher after correcting for errors
      in radon exposure (e.g., 1.02 and 1.11 for the West and the East German study,
      respectively, corrected for an error of size 0.4); ignoring the clear but small
      correlation between radon exposure and smoking of about -0.06 would lead to less
      conservative corrections (1.10 and 1.13 for West and East, respectively).
      Accounting for a realistically sized error in the smoking variable additionally
      increases the OR estimates slightly. Remarkable is the fact that the naive OR
      estimate of the West study of 0.97 exceeds unity after correcting for errors in
      radon exposure larger than 0.3. We conclude that correcting for errors in radon
      exposure has a meaningful impact on OR estimates, that the correlation between
      radon exposure and the smoking variable affects the correction even if the
      smoking variable was error-free, and that such an analysis is extremely valuable
      to grasp an important issue in epidemiology, that is, the dimension of residual
      confounding due to adjusting for an imprecisely measured smoking variable.

PMID- 16608835
TI  - Radon-thoron discriminative measurements in Gansu Province, China, and their
      implication for dose estimates.
AB  - Indoor radon measurements were carried out in cave dwellings of the Chinese loess
      plateau in Gansu province, where previously the Laboratory of Industrial Hygiene
      (LIH), China, and the U.S. National Cancer Institute (NCI) had conducted an
      international collaborative epidemiological study. The LIH-NCI study showed an
      increased lung cancer risk due to high residential radon levels, and estimated
      the excess odds ratio at 100 Bq/m3 to be 0.19 (Wang et al., 2002). The present
      study used two types of newly developed passive monitors: One is a discriminative
      monitor for radon and thoron; the other is a selective monitor for thoron decay
      products. The arithmetic mean concentrations of indoor radon and thoron were 91
      and 351 Bq/m3, respectively. As reported by our previous study in Shanxi and
      Shaanxi provinces (Tokonami et al., 2004), the presence of high thoron
      concentration was confirmed and thoron was predominant over radon in the cave
      dwellings. However, the mean equilibrium equivalent thoron concentration (EETC)
      was found to be much lower than expected when assuming the equilibrium factor of
      0.1 provided by the UNSCEAR (2000) report. The effective dose by radon and thoron
      decay products was estimated to be 3.08 mSv/yr. It was significantly lower than
      the dose of 8.22 mSv/yr estimated from the measurements that did not take into
      consideration any discrimination between radon and thoron. Excess relative risk
      of lung cancer per sievert may be much higher than the risk estimated from the
      LIH-NCI study, considering that discriminative measurements were not used in
      their study.

PMID- 16608836
TI  - Assessment and management of residential radon health risks: a report from the
      health Canada radon workshop.
AB  - Epidemiologic studies of uranium miners and other underground miners have
      consistently shown miners exposed to high levels of radon to be at increased risk
      of lung cancer. More recently, concern has arisen about lung cancer risks among
      people exposed to lower levels of radon in homes. The current Canadian guideline
      for residential radon exposure was set in 1988 at 800 Bq/m(3). Because of the
      accumulation of a considerable body of new scientific evidence on radon lung
      cancer risks since that time, Health Canada sponsored a workshop to review the
      current state-of-the-science on radon health risks. The specific objectives of
      the workshop were (1) to collect and assess scientific information relevant to
      setting national radon policy in Canada, and (2) to gather information on social,
      political, and operational considerations in setting national policy. The
      workshop, held on 3-4 March 2004, was attended by 38 invited scientists,
      regulators, and other stakeholders from Canada and the United States. The
      presentations on the first day dealt primarily with scientific issues. The
      combined analysis of North American residential radon and lung cancer studies was
      reviewed. The analysis confirmed a small but detectable increase in lung cancer
      risk at residential exposure levels. Current estimates suggest that radon in
      homes is responsible for approximately 10% of all lung cancer deaths in Canada,
      making radon the second leading cause of lung cancer after tobacco smoking. This
      was followed by a perspective from an UNSCEAR (United Nations Scientific
      Committee on the Effects of Atomic Radiation) working group on radon. There were
      two presentations on occupational exposures to radon and two presentations
      considered the possibility of radon as a causative factor for cardiovascular
      disease and for cancer in other organs besides the lung. The possible
      contribution of environmental tobacco smoke to lung cancers in nonsmokers was
      also considered. Areas for future research were identified. The second day was
      devoted to policy and operational issues. The presentations began with a
      perspective from the U.S. Environmental Protection Agency, followed by a history
      of radon policy development in Canada. Subsequent presentations dealt with the
      cost-effectiveness of radon mitigation, Canadian building codes and radon, and a
      summary of radon standards from around the world. Provincial representatives and
      a private consultant were given opportunities to present their viewpoints. A
      number of strategies for reducing residential radon exposure in Canada were
      recognized, including testing and mitigation of existing homes (on either a
      widespread or targeted basis) and changing the building code to require that
      radon mitigation devices be installed at the time a new home is constructed. The
      various elements of a comprehensive national radon policy were set forth.

PMID- 16608837
TI  - World Health Organization's International Radon Project.
AB  - Following initial in vitro and in vivo studies and important studies of uranium
      miners, scientists have now completed impressive case-control studies of lung
      cancer risk from exposure to residential radon. Researchers have pooled these
      studies, in which all the information from the individual studies was reanalyzed.
      These pooled analyzes confirm that in the context of residential exposure, radon
      is now an established risk factor for lung cancer. Many of the initial
      uncertainties have been reduced, and health risk assessors are now confident that
      radon may contribute to as much as 10% of the total burden of lung cancer--that
      is, 2% of all cancers in the population, worldwide. To reduce residential radon
      lung cancer risk, national authorities must have methods and tools based on solid
      scientific evidence and sound public health policies. To meet these needs, the
      World Health Organization (WHO) has initiated the WHO International Radon
      Project. This three year project, to be implemented during the period 2005-2008,
      will include (1) a worldwide database on national residential radon levels, radon
      action levels, regulations, research institutions, and authorities; (2) public
      health guidance for awareness-raising and mitigation; and (3) an estimation of
      the global burden of disease (GDB) associated with radon exposure.

PMID- 16608838
TI  - Role of NF-kappaB in regulation of PXR-mediated gene expression: a mechanism for
      the suppression of cytochrome P-450 3A4 by proinflammatory agents.
AB  - It is a long-standing observation that inflammatory responses and infections
      decrease drug metabolism capacity in human and experimental animals. Cytochrome P
      450 3A4 cyp304 is responsible for the metabolism of over 50% of current
      prescription drugs, and cyp3a4 expression is transcriptionally regulated by
      pregnane X receptor (PXR), which is a ligand-dependent transcription factor. In
      this study, we report that NF-kappaB activation by lipopolysaccharide and tumor
      necrosis factor-alpha plays a pivotal role in the suppression of cyp3a4 through
      interactions of NF-kappaB with the PXR.retinoid X receptor (RXR) complex.
      Inhibition of NF-kappaB by NF-kappaB-specific suppressor SRIkappaBalpha reversed
      the suppressive effects of lipopolysaccharide and tumor necrosis factor-alpha.
      Furthermore, we showed that NF-kappaB p65 disrupted the association of the
      PXR.RXRalpha complex with DNA sequences as determined by electrophoretic mobility
      shift assay and chromatin immunoprecipitation assays. NF-kappaB p65 directly
      interacted with the DNA-binding domain of RXRalpha and may prevent its binding to
      the consensus DNA sequences, thus inhibiting the transactivation by the
      PXR.RXRalpha complex. This mechanism of suppression by NF-kappaB activation may
      be extended to other nuclear receptor-regulated systems where RXRalpha is a
      dimerization partner.

PMID- 16608839
TI  - Differential metabolomics reveals ophthalmic acid as an oxidative stress
      biomarker indicating hepatic glutathione consumption.
AB  - Metabolomics is an emerging tool that can be used to gain insights into cellular
      and physiological responses. Here we present a metabolome differential display
      method based on capillary electrophoresis time-of-flight mass spectrometry to
      profile liver metabolites following acetaminophen-induced hepatotoxicity. We
      globally detected 1,859 peaks in mouse liver extracts and highlighted multiple
      changes in metabolite levels, including an activation of the ophthalmate
      biosynthesis pathway. We confirmed that ophthalmate was synthesized from 2
      aminobutyrate through consecutive reactions with gamma-glutamylcysteine and
      glutathione synthetase. Changes in ophthalmate level in mouse serum and liver
      extracts were closely correlated and ophthalmate levels increased significantly
      in conjunction with glutathione consumption. Overall, our results provide a broad
      picture of hepatic metabolite changes following acetaminophen treatment. In
      addition, we specifically found that serum ophthalmate is a sensitive indicator
      of hepatic GSH depletion, and may be a new biomarker for oxidative stress. Our
      method can thus pinpoint specific metabolite changes and provide insights into
      the perturbation of metabolic pathways on a large scale and serve as a powerful
      new tool for discovering low molecular weight biomarkers.

PMID- 16608840
TI  - NADP-dependent mannitol dehydrogenase, a major allergen of Cladosporium herbarum.
AB  - Cladosporium herbarum is an important allergenic fungal species that has been
      reported to cause allergic diseases in nearly all climatic zones. 5-30% of the
      allergic population displays IgE antibodies against molds. Sensitization to
      Cladosporium has often been associated with severe asthma and less frequently
      with chronic urticaria and atopic eczema. However, no dominant major allergen of
      this species has been found so far. We present cloning, production, and
      characterization of NADP-dependent mannitol dehydrogenase of C. herbarum (Cla h
      8) and show that this protein is a major allergen that is recognized by IgE
      antibodies of approximately 57% of all Cladosporium allergic patients. This is
      the highest percentage of patients reacting with any Cladosporium allergen
      characterized so far. Cla h 8 was purified to homogeneity by standard
      chromatographic methods, and both N-terminal and internal amino acid sequences of
      protein fragments were determined. Enzymatic analysis of the purified natural
      protein revealed that this allergen represents a NADP-dependent mannitol
      dehydrogenase that interconverts mannitol and d-fructose. It is a soluble, non
      glycosylated cytoplasmic protein. Two-dimensional protein analysis indicated that
      mannitol dehydrogenase is present as a single isoform. The cDNA encoding Cla h 8
      was cloned from a lambda-ZAP library constructed from hyphae and spores. The
      recombinant non-fusion protein was expressed in Escherichia coli and purified to
      homogeneity. Its immunological and biochemical identity with the natural protein
      was shown by enzyme activity tests, CD spectroscopy, IgE immunoblots with sera of
      patients, and by skin prick testing of Cladosporium allergic patients. This
      protein therefore is a new major allergen of C. herbarum.

PMID- 16608841
TI  - Functional interactions of phospholemman (PLM) (FXYD1) with Na+,K+-ATPase.
      Purification of alpha1/beta1/PLM complexes expressed in Pichia pastoris.
AB  - Human FXYD1 (phospholemman, PLM) has been expressed in Pichia pastoris with
      porcine alpha1/His10-beta1 subunits of Na+,K+-ATPase or alone. Dodecyl-beta
      maltoside-soluble complexes of alpha1/beta1/PLM have been purified by metal
      chelate chromatography, either from membranes co-expressing alpha1,His10-beta1,
      and PLM or by in vitro reconstitution of PLM with alpha1/His10-beta1 subunits.
      Comparison of functional properties of purified alpha1/His10-beta1 and
      alpha1/His10-beta1/PLM complexes show that PLM lowered K0.5 for Na+ ions
      moderately (approximately 30%) but did not affect the turnover rate or Km of ATP
      for activating Na+,K+-ATPase activity. PLM also stabilized the alpha1/His10-beta1
      complex. In addition, PLM markedly (>3-fold) reduced the K0.5 of Na+ ions for
      activating Na+-ATPase activity. In membranes co-expressing alpha1/His10-beta1
      with PLM the K0.5 of Na+ ions was also reduced, compared with the control,
      excluding the possibility that detergent or lipid in purified complexes
      compromise functional interactions. When expressed in HeLa cells with rat alpha1,
      rat PLM significantly raised the K0.5 of Na+ ions, whereas for a chimeric
      molecule consisting of transmembranes segments of PLM and extramembrane segments
      of FXYD4, the K0.5 of Na+ ions was significantly reduced, compared with the
      control. The opposite functional effects in P. pastoris and HeLa cells are
      correlated with endogenous phosphorylation of PLM at Ser68 or unphosphorylated
      PLM, respectively, as detected with antibodies, which recognize PLM
      phosphorylated at Ser68 (protein kinase A site) or unphosphorylated PLM. We
      hypothesize that PLM interacts with alpha1/His10-beta1 subunits at multiple
      locations, the different functional effects depending on the degree of
      phosphorylation at Ser68. We discuss the role of PLM in regulation of Na+,K+
      ATPase in cardiac or skeletal muscle cells.

PMID- 16608842
TI  - Absence of dysferlin alters myogenin expression and delays human muscle
      differentiation "in vitro".
AB  - Mutations in dysferlin cause a type of muscular dystrophy known as
      dysferlinopathy. Dysferlin may be involved in muscle repair and differentiation.
      We compared normal human skeletal muscle cultures expressing dysferlin with
      muscle cultures from dysferlinopathy patients. We quantified the fusion index of
      myoblasts as a measure of muscle development and conducted optic and electronic
      microscopy, immunofluorescence, Western blot, flow cytometry, and real-time PCR
      at different developmental stages. Short interference RNA was used to corroborate
      the results obtained in dysferlin-deficient cultures. A luciferase reporter assay
      was performed to study myogenin activity in dysferlin-deficient cultures.
      Myoblasts fusion was consistently delayed as compared with controls whereas the
      proliferation rate did not change. Electron microscopy showed that control
      cultured cells at 10 days were fusiform, whereas dysferlin-deficient cells were
      star-shaped and large. After 15 days the normal multinucleated appearance and
      structured myofibrils were not present in dysferlin-deficient cells. Strikingly,
      myogenin was not detected in myotubes from dysferlin-deficient cultures using
      Western blot, and mRNA analysis showed low levels (p < 0.05) compared with
      controls. Flow cytometry and immunofluorescence also showed reduced levels of
      myogenin in dysferlin-deficient cultures. When the dysferlin gene was knocked
      down ( approximately 80%), myogenin mRNA leveled down to approximately 70%. MyoD
      and desmin mRNA levels in controls and dysferlin-deficient cultures were similar.
      The reporter luciferase assay demonstrated a low myogenin activity in dysferlin
      deficient cultures. These results point to a functional link between dysferlin
      and myogenin, and both proteins may share a new signaling pathway involved in
      differentiation of skeletal muscle in vitro.

PMID- 16608843
TI  - Nucleophosmin regulates cell cycle progression and stress response in
      hematopoietic stem/progenitor cells.
AB  - Nucleophosmin (NPM) is a multifunctional protein frequently overexpressed in
      actively proliferating cells. Strong evidence indicates that NPM is required for
      embryonic development and genomic stability. Here we report that NPM enhances the
      proliferative potential of hematopoietic stem cells (HSCs) and increases their
      survival upon stress challenge. Both short term liquid culture and clonogenic
      progenitor cell assays show a selective expansion of NPM-overexpressing HSCs.
      Interestingly, HSCs infected with NPM retrovirus show significantly reduced
      commitment to myeloid differentiation compared with vector-transduced cells, and
      majority of the NPM-overexpressing cells remains primitive during a 5-day
      culture. Bone marrow transplantation experiments demonstrate that NPM promotes
      the self-renewal of long term repopulating HSCs while attenuated their commitment
      to myeloid differentiation. NPM overexpression induces rapid entry of HSCs into
      the cell cycle and suppresses the expression of several negative cell cycle
      regulators that are associated with G(1)-to-S transition. NPM knockdown elevates
      expression of these negative regulators and exacerbates stress-induced cell cycle
      arrest. Finally, overexpression of NPM promotes the survival and recovery of HSCs
      and progenitors after exposure to DNA damage, oxidative stress, and hematopoietic
      injury both in vivo and in vitro. DNA repair kinetics study suggests that NPM has
      a role in reducing the susceptibility of chromosomal DNA to damage rather than
      promoting DNA damage repair. Together, these results indicate that NPM plays an
      important role in hematopoiesis via mechanisms involving modulation of
      HSC/progenitor cell cycle progression and stress response.

PMID- 16608844
TI  - Identification of a Ca2+-ATPase in brown adipose tissue mitochondria: regulation
      of thermogenesis by ATP and Ca2+.
AB  - In brown adipose tissue (BAT) adrenaline promotes a rise of the cytosolic Ca(2+)
      concentration from 0.05 up to 0.70 mum. It is not known how the rise of Ca(2+)
      concentration activates BAT thermogenesis. In this report we compared the effects
      of Ca(2+) in BAT and liver mitochondria. Using electron microscopy and
      immunolabeling we identified a sarco/endoplasmic reticulum (ER) Ca(2+)-ATPase
      bound to the inner membrane of BAT mitochondria. A Ca(2+)-dependent ATPase
      activity was detected in BAT mitochondria when the respiratory substrates malate
      and pyruvate were included in the medium. ATP and Ca(2+) enhanced the amount of
      heat produced by BAT mitochondria during respiration. The Ca(2+) concentration
      needed for half-maximal activation of the ATPase activity and rate of heat
      production were the same and varied between 0.1 and 0.2 mum. Heat production was
      partially inhibited by the proton ionophore carbonyl cyanide p
      trifluoromethoxyphenylhydrazone and abolished by thapsigargin, a specific ER
      Ca(2+)-ATPase inhibitor, and by both rotenone and KCN, two substances that
      inhibit the electron transfer trough the mitochondrial cytochrome chain. In liver
      mitochondria Ca(2+) did not stimulate the ATPase activity nor increase the rate
      of heat production. Thapsigargin had no effect on liver mitochondria. In
      conclusion, this is the first report of a Ca(2+)-ATPase in mitochondria that is
      BAT-specific and can generate heat in the presence of Ca(2+) concentrations
      similar to those noted in the cell during adrenergic stimulation.

PMID- 16608845
TI  - Identification of functionally relevant residues of the rat ileal apical sodium
      dependent bile acid cotransporter.
AB  - The mechanisms underlying the transport of bile acids by apical sodium-dependent
      bile acid transporter (Asbt) are not well defined. To further identify the
      functionally relevant residues, thirteen conserved negatively (Asp and Glu) and
      positively (Lys and Arg) charged residues plus Cys-270 of rat Asbt were replaced
      with Ala or Gln by site-directed mutagenesis. Seven of the fourteen residues of
      rat Asbt were identified as functionally important by taurocholate transport
      studies, substrate inhibition assays, confocal microscopy, and
      electrophysiological methods. The results showed that Asp-122, Lys-191, Lys-225,
      Lys-256, Glu-261, and Lys-312,Lys-313 residues of rat Asbt are critical for
      transport function and may determine substrate specificity. Arg-64 may be located
      at a different binding site to assist in interaction with non-bile acid organic
      anions. For bile acid transport by Asbt, Na(+) ion movement is a voltage
      dependent process that tightly companied with taurocholate movement. Asp-122 and
      Glu-261 play a critical role in the interaction of a Na(+) ion and ligand with
      Asbt. Cys-270 is not essential for the transport process. These studies provide
      new details about the amino acid residues of Asbt involved in binding and
      transport of bile acids and Na(+).

PMID- 16608846
TI  - A "petite obligate" mutant of Saccharomyces cerevisiae: functional mtDNA is
      lethal in cells lacking the delta subunit of mitochondrial F1-ATPase.
AB  - Within the mitochondrial F(1)F(0)-ATP synthase, the nucleus-encoded delta-F(1)
      subunit plays a critical role in coupling the enzyme proton translocating and ATP
      synthesis activities. In Saccharomyces cerevisiae, deletion of the delta subunit
      gene (Deltadelta) was shown to result in a massive destabilization of the
      mitochondrial genome (mitochondrial DNA; mtDNA) in the form of 100% rho(-)/rho
      degrees petites (i.e. cells missing a large portion (>50%) of the mtDNA (rho(-))
      or totally devoid of mtDNA (rho degrees )). Previous work has suggested that the
      absence of complete mtDNA (rho(+)) in Deltadelta yeast is a consequence of an
      uncoupling of the ATP synthase in the form of a passive proton transport through
      the enzyme (i.e. not coupled to ATP synthesis). However, it was unclear why or
      how this ATP synthase defect destabilized the mtDNA. We investigated this
      question using a nonrespiratory gene (ARG8(m)) inserted into the mtDNA. We first
      show that retention of functional mtDNA is lethal to Deltadelta yeast. We further
      show that combined with a nuclear mutation (Deltaatp4) preventing the ATP
      synthase proton channel assembly, a lack of delta subunit fails to destabilize
      the mtDNA, and rho(+) Deltadelta cells become viable. We conclude that Deltadelta
      yeast cannot survive when it has the ability to synthesize the ATP synthase
      proton channel. Accordingly, the rho(-)/rho degrees mutation can be viewed as a
      rescuing event, because this mutation prevents the synthesis of the two mtDNA
      encoded subunits (Atp6p and Atp9p) forming the core of this channel. This is the
      first report of what we have called a "petite obligate" mutant of S. cerevisiae.

PMID- 16608847
TI  - PUMA Dissociates Bax and Bcl-X(L) to induce apoptosis in colon cancer cells.
AB  - PUMA is a BH3-only Bcl-2 family protein that plays an essential role in DNA
      damage-induced apoptosis. PUMA interacts with anti-apoptotic Bcl-2 and Bcl-X(L)
      and is dependent on Bax to induce apoptosis. In this study, we investigated how
      the interactions of PUMA with the antiapoptotic proteins coordinate with Bax to
      initiate apoptosis in HCT116 colon cancer cells. We found that Bcl-X(L) was most
      effective among several antiapoptotic proteins in suppressing PUMA-induced
      apoptosis and PUMA-dependent apoptosis induced by the DNA-damaging agent
      adriamycin. Mutant Bcl-X(L) that cannot interact with Bax was unable to protect
      cells from PUMA-mediated apoptosis. Knockdown of Bcl-X(L) by RNA interference
      significantly enhanced PUMA-mediated apoptosis in HCT116 cells but not in PUMA
      knockout cells. Furthermore, Bax was found to be dissociated preferentially from
      Bcl-X(L) in HCT116 cells but not in the PUMA-knockout cells, in response to PUMA
      induction and adriamycin treatment. PUMA inhibited the association of Bax and Bcl
      X(L) in vitro by directly binding to Bcl-X(L) through its BH3 domain. Finally, we
      found that wild-type Bax, but not mutant Bax deficient in either multimerization
      or mitochondrial localization, was able to restore PUMA-induced apoptosis in the
      BAX-knockout cells. Together, these results indicate that PUMA initiates
      apoptosis in part by dissociating Bax and Bcl-X(L), thereby promoting Bax
      multimerization and mitochondrial translocation.

PMID- 16608848
TI  - Laminin alpha 3 forms a complex with beta3 and gamma3 chains that serves as the
      ligand for alpha 6beta1-integrin at the apical ectoplasmic specialization in
      adult rat testes.
AB  - Apical ectoplasmic specialization (ES) is a testis-specific hybrid cell/cell
      actin-based adherens junction and cell/matrix focal contact anchoring junction
      type restricted to the interface between Sertoli cells and developing spermatids.
      Recent studies have shown that laminin gamma3, restricted to elongating
      spermatids, is a putative binding partner of alpha 6beta 1-integrin localized in
      Sertoli cells at the apical ES. However, the identity of the alpha and beta
      chains, which constitute a functional laminin ligand with the gamma3 chain at the
      apical ES, is not known. Using reverse transcription-PCR and immunoblotting to
      survey all laminin chains in cells of the seminiferous epithelium, it was noted
      that alpha 2, alpha 3, beta1, beta2, beta3, and gamma3 chains were found in germ
      cells, whereas alpha 1, alpha 2, alpha 4, alpha 5, beta1, beta2, gamma1, gamma2,
      and gamma3 chains were found in Sertoli cells, implying that alpha 3 and beta3
      are the plausible laminin chains restricted to germ cells that may be the bona
      fide partners of gamma3. To verify this postulate, recombinant proteins based on
      domain G of alpha 3 and domain I of beta3 and gamma3 chains were produced and
      used to obtain the corresponding specific polyclonal antibodies. Additional
      studies have demonstrated that the laminin alpha 3, beta3, and gamma3 chains
      indeed are restricted to germ cells at the apical ES, co-localizing with each
      other and with beta1-integrin. Furthermore, co-immunoprecipitation studies have
      confirmed the interactions among laminin alpha 3, beta3, and gamma3, as well as
      beta1-integrin. When the functional laminin ligand at the apical ES was disrupted
      via blocking antibodies, such as using anti-laminin alpha 3 or gamma3 IgG, this
      treatment perturbed adhesion between Sertoli and germ cells (mostly spermatids),
      leading to germ cell loss from the epithelium. More important, a transient
      disruption of the blood-testis barrier was also detected.

PMID- 16608849
TI  - A pool of extramitochondrial frataxin that promotes cell survival.
AB  - Frataxin is a mitochondrial protein involved in iron metabolism. Defective
      expression of frataxin causes Friedreich ataxia (FA), an inherited degenerative
      syndrome characterized by ataxia, cardiomyopathy, and high incidence of diabetes.
      Here we report that frataxin-deficient cells are more prone to undergo stress
      induced mitochondrial damage and apoptosis, while the overexpression of frataxin
      confers protection to a variety of cell types. Moreover, we reveal the existence
      of an extramitochondrial pool of frataxin, which can efficiently prevent
      mitochondrial damage and apoptosis in different cellular systems. Remarkably,
      extramitochondrial frataxin can fully replace mitochondrial frataxin in promoting
      survival of FA cells.

PMID- 16608850
TI  - Characterization of a family of nucleolar SUMO-specific proteases with preference
      for SUMO-2 or SUMO-3.
AB  - SUMOylation is a reversible process regulated by a family of sentrin/SUMO
      specific proteases (SENPs). Of the six SENP family members, except for SENP1 and
      SENP2, the substrate specificities of the rest of SENPs are not well defined.
      Here, we have described SENP5, which has restricted substrate specificity. SENP5
      showed SUMO-3 C-terminal hydrolase activity but could not process pro-SUMO-1 in
      vitro. Furthermore, SENP5 showed more limited isopeptidase activity in vitro. In
      vivo, SENP5 showed isopeptidase activity against SUMO-2 and SUMO-3 conjugates but
      not against SUMO-1 conjugates. Native SENP5 localized mainly to the nucleolus but
      was also found in the nucleus. The N terminus of SENP5 contains a stretch of
      amino acids responsible for the nucleolar localization of SENP5. N-terminal
      truncated SENP5 co-localized with PML, a known SUMO substrate. Using PML
      SUMOylation mutants as model substrates, we showed that SENP5 can remove poly
      SUMO-2 or poly-SUMO-3 from the Lys160 or Lys490 positions of PML. However, SENP5
      could not remove SUMO-1 from the Lys160 or Lys490 positions of PML. Nonetheless,
      SENP5 could remove SUMO-1, -2, and -3 from the Lys65 position of PML. Thus, SENP5
      also possesses limited SUMO-1 isopeptidase activity. We were also able to show
      that SENP3 has substrate specificity similar to that of SENP5. Thus, SENP3 and
      SENP5 constitute a subfamily of SENPs that regulate the formation of SUMO-2 or
      SUMO-3 conjugates and, to a less extent, SUMO-1 modification.

PMID- 16608851
TI  - Coxsackievirus protein 2BC blocks host cell apoptosis by inhibiting caspase-3.
AB  - Virus infection may induce host cell death by apoptosis, but some DNA viruses are
      capable of preventing this process. RNA viruses were thought not to display anti
      apoptotic activities, as their spread appears to benefit from a rapid induction
      of cell death. Here, we report an antiapoptotic activity in the Picornavirus
      Coxsackievirus B4 (CVB4). CVB4 infection of HeLa cells induced negligible
      apoptosis over a period of 10 h. However, infected cells developed resistance to
      drug-induced apoptosis using staurosporine and actinomycin D and to death
      receptor-induced apoptosis using tumor necrosis factor-related apoptosis-inducing
      ligand. Despite this resistance, the apoptotic machinery was nonetheless fully
      activated in these drug-treated infected cells because the levels of pro-caspase
      3 processing to its active form were similar to control cells. However, the
      DEVDase (Asp-Glu-Val-Asp protease) activity of the processed caspase was
      significantly inhibited in the virus-infected staurosporine-treated cells
      compared with drug treatment alone. Likewise, extracts of CVB4-infected cells
      suppressed recombinant caspase-3 activity in vitro. Immunoprecipitation of
      activated caspase-3 from radiolabeled virus-infected cells revealed the co
      precipitation of a 48-kDa protein that was tentatively identified as viral
      protein 2BC. Recombinant caspase-3 was found to co-precipitate with virus protein
      2BC. Finally, when protein 2BC was expressed in HeLa cells, both staurosporine
      induced apoptosis and in vitro caspase-3 DEVDase activity were significantly
      reduced. Taken together these data imply that CVB4 infection suppresses apoptosis
      through virus protein 2BC associating with caspase-3 and inhibiting its function.
      Thus, 2BC is the first reported RNA virus inhibitor of apoptosis protein.

PMID- 16608852
TI  - Membrane accumulation of influenza A virus hemagglutinin triggers nuclear export
      of the viral genome via protein kinase Calpha-mediated activation of ERK
      signaling.
AB  - Replication and transcription of the influenza virus genome takes place
      exclusively within the nucleus of the infected cells. The viral RNA genome,
      polymerase subunits, and nucleoprotein form ribonucleoprotein (RNP) complexes.
      Late in the infectious cycle RNPs have to be exported from the nucleus to be
      enwrapped into budding progeny virions at the cell membrane. This process
      requires viral activation of the cellular Raf/MEK/ERK (mitogen-activated protein
      kinase (MAPK)) signaling cascade that is activated late in the infection cycle.
      Accordingly, block of the cascade results in retardation of RNP export and
      reduced titers of progeny virus. In the present study we have analyzed the
      importance of cell-membrane association of the viral hemagglutinin glycoprotein
      for viral MAPK activation. We show that hemagglutinin membrane accumulation and
      its tight association with lipid-raft domains trigger activation of the MAPK
      cascade via protein kinase Calpha activation and induces RNP export. This may
      represent an auto-regulative mechanism that coordinates timing of RNP export to a
      point when all viral components are ready for virus budding.

PMID- 16608853
TI  - A novel, topologically constrained DNA molecule containing a double Holliday
      junction: design, synthesis, and initial biochemical characterization.
AB  - The double Holliday junction (dHJ) is a central intermediate to homologous
      recombination, but biochemical analysis of the metabolism of this structure has
      been hindered by the lack of a substrate that adequately replicates the
      endogenous structure. We have synthesized a novel dHJ substrate that consists of
      two small, double stranded DNA circles conjoined by two Holliday junctions (HJs).
      Its biochemical synthesis is based on the production of two pairs of single
      stranded circles from phagemids, followed by their sequential annealing with
      reverse gyrase. The sequence between the two HJs is identical on both strands,
      allowing the HJs to migrate without the generation of unpaired regions of DNA,
      whereas the distance between the HJs is on the order of gene conversion tracts
      thus far measured in Drosophila and mouse model systems. The structure of this
      substrate also provides similar topological constraint as would occur in an
      endogenous dHJ. Digestion of the dHJ substrate by T7 endonuclease I resolves the
      substrate into crossover and non-crossover products, as predicted by the Szostak
      model of double strand break repair. This substrate will greatly facilitate the
      examination of the mechanism of resolution of double Holliday junctions.

PMID- 16608854
TI  - Mechanism of proliferating cell nuclear antigen clamp opening by replication
      factor C.
AB  - The eukaryotic replication factor C (RFC) clamp loader is an AAA+ spiral-shaped
      heteropentamer that opens and closes the circular proliferating cell nuclear
      antigen (PCNA) clamp processivity factor on DNA. In this study, we examined the
      roles of individual RFC subunits in opening the PCNA clamp. Interestingly, Rfc1,
      which occupies the position analogous to the delta clamp-opening subunit in the
      Escherichia coli clamp loader, is not required to open PCNA. The Rfc5 subunit is
      required to open PCNA. Consistent with this result, Rfc2.3.4.5 and Rfc2.5
      subassemblies are capable of opening and unloading PCNA from circular DNA. Rfc5
      is positioned opposite the PCNA interface from Rfc1, and therefore, its action
      with Rfc2 in opening PCNA indicates that PCNA is opened from the opposite side of
      the interface that the E. coli delta wrench acts upon. This marks a significant
      departure in the mechanism of eukaryotic and prokaryotic clamp loaders.
      Interestingly, the Rad.RFC DNA damage checkpoint clamp loader unloads PCNA clamps
      from DNA. We propose that Rad.RFC may clear PCNA from DNA to facilitate shutdown
      of replication in the face of DNA damage.

PMID- 16608855
TI  - A conformational switch in vinculin drives formation and dynamics of a talin
      vinculin complex at focal adhesions.
AB  - Dynamic interactions between the cytoskeleton and integrins control cell
      adhesion, but regulatory mechanisms remain largely undefined. Here, we tested the
      extent to which the autoinhibitory head-tail interaction (HTI) in vinculin
      regulates formation and lifetime of the talin-vinculin complex, a proposed
      mediator of integrin-cytoskeleton bonds. In an ectopic recruitment assay,
      mutational reduction of HTI drove assembly of talin-vinculin complexes, whereas
      ectopic complexes did not form between talin and wild-type vinculin. Moreover,
      reduction of HTI altered the dynamic assembly of vinculin and talin in focal
      adhesions. Using fluorescence recovery after photobleaching, we show that the
      focal adhesion residency time of vinculin was enhanced up to 3-fold by HTI
      mutations. The slow dynamics of vinculin correlated with exposure of its cryptic
      talin-binding site, and a talin-binding site mutation rescued the dynamics of
      activated vinculin. Significantly, HTI-deficient vinculin inhibited the focal
      adhesion dynamics of talin, but not paxillin or alpha-actinin. These data show
      that talin conformation in cells permits vinculin binding, whereas the
      autoinhibited conformation of vinculin constitutes the barrier to complex
      formation. Down-regulation of HTI in vinculin to Kd approximately 10(-7) is
      sufficient to induce talin binding, and HTI is essential to the dynamics of
      vinculin and talin at focal adhesions. We therefore conclude that vinculin
      conformation, as modulated by the strength of HTI, directly regulates the
      formation and lifetime of talin-vinculin complexes in cells.

PMID- 16608856
TI  - Estrogen-occupied estrogen receptor represses cyclin G2 gene expression and
      recruits a repressor complex at the cyclin G2 promoter.
AB  - Estrogens, acting through their nuclear receptors have a broad impact on target
      cells, eliciting a transcriptional response program that involves gene repression
      as well as gene stimulation. While much is known about the mechanisms by which
      the estrogen-occupied estrogen receptor (ER) stimulates gene expression, the
      molecular events that lead to gene repression by the hormone-ER complex are
      largely unknown. Because estradiol represses expression of the cyclin G2 gene,
      which encodes a negative regulator of the cell cycle, our aim was to understand
      the mechanism by which cyclin G2 is repressed by estrogen. We show that cyclin G2
      is a primary ER target gene in MCF-7 breast cancer cells that is rapidly and
      robustly down-regulated by estrogen. Promoter analysis reveals a responsive
      region containing a half-estrogen response element and GC-rich region that
      interact with ER and Sp1 proteins. Mutation of the half-ERE abrogates hormone
      mediated repression. Mutational mapping of receptor reveals a requirement for its
      N-terminal region and DNA binding domain to support cyclin G2 repression.
      Following estradiol treatment of cells, chromatin immunoprecipitation analyses
      reveal recruitment of ER to the cyclin G2 regulatory region, dismissal of RNA
      polymerase II, and recruitment of a complex containing N-CoR and histone
      deacetylases, leading to a hypoacetylated chromatin state. Our study provides
      evidence for a mechanism by which the estrogen-occupied ER is able to actively
      repress gene expression in vivo and indicates a role for nuclear receptor
      corepressors and associated histone deacetylase activity in mediating negative
      gene regulation by this hormone-occupied nuclear receptor.

PMID- 16608857
TI  - Keratin 20 serine 13 phosphorylation is a stress and intestinal goblet cell
      marker.
AB  - Keratin polypeptide 20 (K20) is an intermediate filament protein with
      preferential expression in epithelia of the stomach, intestine, uterus, and
      bladder and in Merkel cells of the skin. K20 expression is used as a marker to
      distinguish metastatic tumor origin, but nothing is known regarding its
      regulation and function. We studied K20 phosphorylation as a first step toward
      understanding its physiologic role. K20 phosphorylation occurs preferentially on
      serine, with a high stoichiometry as compared with keratin polypeptides 18 and
      19. Mass spectrometry analysis predicted that either K20 Ser(13) or Ser(14) was a
      likely phosphorylation site, and Ser(13) was confirmed as the phospho-moiety
      using mutation and transfection analysis and generation of an anti-K20-phospho
      Ser(13) antibody. K20 Ser(13) phosphorylation increases after protein kinase C
      activation, and Ser(13)-to-Ala mutation interferes with keratin filament
      reorganization in transfected cells. In physiological contexts, K20 degradation
      and associated Ser(13) hyperphosphorylation occur during apoptosis, and
      chemically induced mouse colitis also promotes Ser(13) phosphorylation. Among
      mouse small intestinal enterocytes, K20 Ser(13) is preferentially phosphorylated
      in goblet cells and undergoes dramatic hyperphosphorylation after starvation and
      mucin secretion. Therefore, K20 Ser(13) is a highly dynamic protein kinase C
      related phosphorylation site that is induced during apoptosis and tissue injury.
      K20 Ser(13) phosphorylation also serves as a unique marker of small intestinal
      goblet cells.

PMID- 16608858
TI  - Phospholipase D1 regulates cell migration in a lipase activity-independent
      manner.
AB  - Cell migration, a complex biological process, requires dynamic cytoskeletal
      remodeling. Phospholipase D (PLD) generates phosphatidic acid, a lipid second
      messenger. Although PLD activity has been proposed to play a role in cytoskeletal
      rearrangement, the manner in which PLD participates in the rearrangement process
      remains obscure. In this study, by silencing endogenous PLD isozymes using small
      interfering RNA in HeLa cells, we demonstrate that endogenous PLD1 is required
      for the normal organization of the actin cytoskeleton, and, more importantly, for
      cell motility. PLD1 silencing in HeLa cells resulted in dramatic changes in
      cellular morphology, including the accumulation of stress fibers, as well as cell
      elongation and flattening, which appeared to be caused by an increased number of
      focal adhesions, which ultimately culminated in enhanced cell-substratum
      interactions. Accordingly, serum-induced cell migration was profoundly inhibited
      by PLD1-silencing. Moreover, the augmented cell substratum interaction and
      retarded cell migration induced by PLD1-silencing could be restored by the adding
      back not only of wild type, but also of lipase-inactive PLD1 into knockdown
      cells. Taken together, our results strongly suggest that endogenous PLD1 is a
      critical factor in the organization of the actin-based cytoskeleton, with regard
      to cell adhesion and migration. These effects of PLD1 appear to operate in a
      lipase activity-independent manner. We also discuss the regulation of Src family
      kinases by PLD1, as related to the modulation of Pyk2 and cell migration.

PMID- 16608859
TI  - Optimizing use of revascularization and clinical outcomes in ST-elevation
      myocardial infarction: insights from the GUSTO-V trial.
AB  - AIMS: To examine the relationship between revascularization within 7 days and 1
      year mortality among ST-elevation myocardial infarction patients enrolled in
      GUSTO-V trial (n=13 451). To examine the relative contribution of system and
      patient level factors to the variation in international revascularization rates,
      and their impact on mortality outcomes. METHODS AND RESULTS: Patients from North
      America (USA, Canada), Australia, and Europe (UK, France, Germany, Italy, Spain,
      Poland, Norway, The Netherlands, Belgium, Finland) were included in the study.
      Revascularization was associated with lower 1-year mortality. Norway, Belgium,
      Spain, Poland, and Italy also had lower than expected revascularization rates but
      higher than expected mortality rates. France and USA had almost two times the
      expected rate of 7-day revascularization, which was associated with modest
      mortality benefits. Patients' propensity for revascularization based on clinical
      factors alone was associated with lower 1-year mortality (OR 0.97, 95% CI: 0.96
      0.99). Country-level factors had an impact on propensity for revascularization
      but no impact on 1-year mortality. CONCLUSION: Our study reveals the potential
      for some countries with lower than expected 7-day revascularization rates to
      improve their clinical outcomes. Also highlighted is the possibility for more
      economically efficient delivery of care in USA and France.

PMID- 16608860
TI  - Strict blood glucose control with insulin during intensive care after cardiac
      surgery: impact on 4-years survival, dependency on medical care, and quality-of
      life.
AB  - AIMS: To document the impact of intensive insulin therapy during intensive care
      on long-term (4 years) outcome of high-risk cardiac surgery patients. METHODS AND
      RESULTS: In this pre-planned sub-analysis and follow-up study of a large,
      randomized controlled trial on the effects of intensive insulin therapy during
      critical illness, we assessed long-term outcome in the 970 patients who had been
      admitted after high-risk cardiac surgery (mean+/-SD EuroSCORE of 6.0+/-3.7;
      EuroSCORE-predicted hospital mortality of 9.9%; observed hospital mortality of
      7.5% in the conventional insulin group and 3.4% in the intensive insulin group).
      Long-term outcome was quantified as: (a) 4 years survival; (b) incidence of
      hospital re-admission; (c) level of activity and medical care requirements at 4
      years as assessed by the Karnofsky score; and (d) perceived health-related
      quality-of-life at 4 years as assessed by the Nottingham Health Profile. Four
      years after ICU admission, the number of post-hospital discharge deaths was
      similar in the two study groups, reflecting maintenance of the acute survival
      benefit with intensive insulin therapy. Survivors who had been treated with
      intensive insulin during ICU stay revealed a similar risk for hospital re
      admission and a comparable level of dependency on medical care. There was no
      effect on quality-of-life in the total group, whereas the increased survival of
      sicker patients with at least 3 days of insulin therapy evoked a more compromised
      perceived quality-of-life, in particular regarding social and family life.
      CONCLUSION: The short-term survival benefit obtained with insulin-titrated
      glycaemic control during intensive care after cardiac surgery was maintained
      after 4 years, without inducing increased medical care requirements but possibly
      at the expense of compromised perceived quality of social and family life.

PMID- 16608861
TI  - Charge of the right brigade? Communities, coverage, and care for the uninsured.
AB  - The Robert Wood Johnson Foundation's Communities in Charge (CIC) program funded
      projects in fourteen communities that aimed to expand health insurance coverage
      and improve care for their uninsured residents. Our examination of seven program
      sites suggests that despite solid community leadership and carefully crafted
      plans, political, economic, and organizational obstacles precluded much expansion
      of coverage and constrained reforms. Redistribution of financial and
      organizational resources among both mainstream and safety-net institutions in
      these communities was hard to achieve. CIC's record offers little evidence that
      communities are better equipped than are other sectors of U.S. society to solve
      the problem of uninsurance.

PMID- 16608862
TI  - Impermanent politics: the Hillsborough County health care plan and community
      innovation for the uninsured.
AB  - Most communities support their safety-net facilities, but few supply health
      coverage for uninsured residents. In 1991 Hillsborough County, Florida, created a
      health care plan that raised the sales tax by a half-cent, used the proceeds to
      cover about 30,000 uninsured county residents, and assured the public that this
      would save money. In time, however, various conflicts combined to call into
      question the plan's ends and means. These challenges reinvigorated advocacy by
      the plan's supporters, who steered the adoption of changes that seemed to have
      "institutionalized" it. Community-based reformers might find this local
      innovation instructive as they ponder how to build enduring programs.

PMID- 16608863
TI  - Community approaches to providing care for the uninsured.
AB  - Faced with rising uninsurance rates and little response at the state or federal
      levels in recent years, communities have developed various strategies to provide
      care for uninsured people. This paper profiles local strategies in the Community
      Tracking Study sites, focusing on efforts that go beyond traditional safety-net
      access. Our findings suggest that more-recent community efforts--which tend to be
      privately sponsored--are relatively modest in scope compared with more-mature
      programs that enjoy public financing. Although local strategies can fill some
      holes, communities often do not have the resources necessary to fully address the
      problems of the uninsured on their own.

PMID- 16608864
TI  - Applying lessons learned in communities to programs and policies at the federal
      level.
AB  - As solutions to the problems of the uninsured are debated, there are lessons to
      be learned from community-based initiatives. Such efforts can provide information
      on different models as well as key political lessons. Defining the specific role
      that community efforts play is also critical. Actively involving community
      stakeholders of such community initiatives in health care policy debates will
      result in more workable policies.

PMID- 16608865
TI  - Who enrolls in community-based programs for the uninsured, and why do they stay?
AB  - Faced with growing numbers of uninsured people, many communities are developing
      local programs to provide coverage or improve access. Some might predict that
      only those with health problems would participate; however, little is known about
      who enrolls. This paper examines participation and retention in three different
      community programs aimed at low-income uninsured adults. In two of the three
      programs, the typical participant had no health problems. Improved access to
      preventive and routine physician care, and increased security about getting
      access to care should the need arise, appeared to be the primary benefits of both
      initial and continued enrollment.

PMID- 16608866
TI  - The role of a zinc finger-containing glycine-rich RNA-binding protein during the
      cold adaptation process in Arabidopsis thaliana.
AB  - The mechanistic role of a glycine-rich RNA-binding protein designated atRZ-1a
      that contributes to enhance cold tolerance in Arabidopsis was investigated.
      Overexpression of atRZ-1a did not affect the expression of various cold
      responsive genes such as COR6.6, COR15a, COR47, RD29A, RD29B and LTI29. Proteome
      analyses revealed that overexpression of atRZ-1a modulated the expression of
      several stress-responsive genes, and the transcript levels and RNA stability of
      these target genes were not affected by atRZ-1a. atRZ-1a successfully complements
      the cold sensitivity of Escherichia coli lacking four cold shock proteins. These
      results strongly suggest that atRZ-1a plays a role as an RNA chaperone during the
      cold adaptation process.

PMID- 16608867
TI  - Increase of homologous recombination frequency in vascular tissue of Arabidopsis
      plants exposed to salt stress.
AB  - Here we analyzed the influence of salt stress on plant genome stability.
      Homologous recombination events were detected in transgenic Arabidopsis plants
      that carried in their genome a beta-glucuronidase recombination marker.
      Recombination events were scored as blue sectors using a stereo microscope.
      Exposure to 50 mM salt resulted in a 3.0-fold increase in recombination
      frequency. To analyze the organ and tissue specificity of recombination events,
      we examined cross-sections of leaves, stems and roots. We found that nearly 30%
      of recombination events in plants grown under normal conditions and nearly 50% of
      events in plants grown on salt were undetected by the conventional method. Most
      of the recombination events represented a cluster/group of cells (12 on average),
      although events with single cells were also detected. Recombination events were
      very frequent in leaf mesophyll cells. On average, individual recombination
      events located on leaves contained more cells than events located on roots or
      stems. Analysis of recombination events in cross-sectioned tissue of salt-treated
      plants revealed a shift in the distribution of recombination events towards the
      vascular tissue. We discuss the significance of the finding for plant stress
      physiology.

PMID- 16608868
TI  - Nitrate reductase is responsible for elicitin-induced nitric oxide production in
      Nicotiana benthamiana.
AB  - Recent works have established a key role for nitric oxide (NO) in activating
      disease resistance in plants. Nitrate reductase (NR) is one of the enzymes that
      are capable of producing NO in plants. In a previous study, we reported that
      pathogen signals induce expression of NR genes in potato, suggesting the
      involvement of NR in NO production induced by pathogen signals. In this study, we
      cloned NR genes from Nicotiana benthamiana and investigated their involvement in
      NO production induced by INF1, a major elicitin secreted by Phytophthora
      infestans. Treatment of protoplasts prepared from N. benthamiana leaves with INF1
      elevated NO production to a maximum level 1-3 h after treatment. INF1-induced NO
      generation was suppressed completely by an NO-specific scavenger, but partially
      by a nitric oxide synthase inhibitor. To investigate the involvement of NR in
      INF1-induced NO production, NR genes were silenced by virus-induced gene
      silencing. The NR-silenced plants showed yellowish leaves which resemble the
      characteristic of Arabidopsis NR double mutants. Silencing of NR genes
      significantly decreased both NO(2) (-)-producing activity and INF1-induced NO
      production, indicating that NR is involved in INF1-induced NO production. In
      contrast, overexpression of NbNR1 encoding N. benthamiana NR by Agrobacterium
      mediated transient expression elevated NO(2) (-)-producing activity nine times
      over the control; however, INF1-induced NO production in protoplasts
      overexpressing NbNR1 was comparable with that in control protoplasts. These
      results suggest that NR is involved in INF1-induced NO production, and post
      translational modification of NR or availability of substrate NO(2) (-) may be a
      rate-limiting step of NO production by NR.

PMID- 16608869
TI  - Exogenous application of glycinebetaine increases chilling tolerance in tomato
      plants.
AB  - Tomato (Lycopersicon esculentum Mill. cv. Moneymaker) plants are chilling
      sensitive, and do not naturally accumulate glycinebetaine (GB), a metabolite that
      functions as a stress protectant. We reported previously that exogenous GB
      application enhanced chilling tolerance in tomato. To understand its protective
      role better, we have further evaluated various parameters associated with
      improved tolerance. Although its effect was most pronounced in younger plants,
      this benefit was diminished 1 week after GB application. When administered by
      foliar spray, GB was readily taken up and translocated to various organs, with
      the highest levels being measured in meristematic tissues, including the shoot
      apices and flower buds. In leaves, the majority of endogenous GB was found in the
      cytosol; only 0.6-22.0% of the total leaf GB was localized in chloroplasts.
      Immediately after GB application, levels of H(2)O(2), catalase activity and
      expression of the catalase gene (CAT1) were all higher in GB-treated than in
      control plants. One day after exposure to chilling stress, the treated plants had
      significantly greater catalase activity and CAT1 expression, although their
      H(2)O(2) levels remained unchanged. During the following 2 d of this chilling
      treatment, GB-treated plants maintained lower H(2)O(2) levels but had higher
      catalase activity than the controls. These results suggest that, in addition to
      protecting macromolecules and membranes directly, GB-enhanced chilling tolerance
      may involve the induction of H(2)O(2)-mediated antioxidant mechanisms, e.g.
      enhanced catalase expression and catalase activity.

PMID- 16608870
TI  - The GP's response to pandemic influenza: a qualitative study.
AB  - BACKGROUND: Current pandemic influenza plans to place GPs at the front line of a
      pandemic influenza response. However, little is known about GPs' perceptions of
      their role and preparedness in the event of a pandemic occurring. OBJECTIVE: Our
      aim was to assess general practice preparedness to respond to pandemic influenza
      and to identify issues that need to be addressed to enhance preparedness for the
      next pandemic. METHODS: We conducted a series of semi-structured interviews to
      explore GPs' views regarding their role in responding to pandemic influenza,
      practice preparedness and planning issues, and the expectations and requirements
      of GPs for provision of professional services during a pandemic. The subjects
      were 60 Australian GPs, purposively selected to maximize diversity within the
      sample. RESULTS: GPs in this study expressed a willingness to provide
      professional services in a pandemic. The motivation for this was largely
      altruistic and was in the context of high personal risk of becoming infected.
      Participants did not have stockpiles of antivirals or personal protective
      equipment within their practices and felt that government had a duty of care to
      stockpile on behalf of the general practice workforce. Participants were
      enthusiastic about receiving further information and training in pandemic
      preparedness. The most appropriate setting for this was within practices.
      CONCLUSIONS: GPs were willing to provide clinical services in a pandemic.
      However, appropriate education, training and supply of equipment were necessary
      to support them in this role. This information will inform further planning for
      the public health response to pandemic influenza.

PMID- 16608871
TI  - Perceptions of family history across common diseases: a qualitative study in
      primary care.
AB  - BACKGROUND: Having an affected relative is a strong predictor of an individual's
      lifetime risk of developing many diseases. In primary care this is of importance
      in preventive healthcare. AIM: To compare and contrast perceptions of family
      history across common diseases among primary care patients using the theoretical
      framework of Leventhal's Common Sense Model (CSM). METHODS: Thirty semi
      structured interviews were conducted with patients identified in general
      practice, who had a family history of either cancer, heart disease or diabetes.
      We performed qualitative constant comparative analysis of transcript data.
      RESULTS: People with a family history of cancer had a greater sense of personal
      vulnerability than people with a family history of heart disease: family history
      of diabetes was generally viewed as the least threatening. Using the CSM
      constructs we identified factors which determine individual perceptions of family
      history. Beliefs about consequences and timeline were influenced by witnessing
      painful, lingering or sudden familial death; people who felt their risk was
      determined by inheritance were more likely to feel vulnerable and have less
      control, while those who felt able to change lifestyle or behaviour felt more
      able to control their perceived risk. CONCLUSION: Factors influencing perceptions
      of family history may vary between individuals and between diseases. To use the
      family history as a tool in preventive healthcare we will need to consider the
      individual's personal understanding of disease risk and their ideas about cause
      and controllability of the familial illness. Perceived risk may then be used to
      motivate preventive health behaviours.

PMID- 16608872
TI  - Plgf-/-eNos-/- mice show defective angiogenesis associated with increased
      oxidative stress in response to tissue ischemia.
AB  - Neo-angiogenesis is a complex phenomenon modulated by the concerted action of
      several molecular factors. We have generated a congenic line of knockout mice
      carrying null mutations of both placental growth factor (PlGF) and endothelial
      nitric oxide synthase (eNOS), two genes that play a pivotal role in the
      regulation of pathological angiogenesis. In the present study, we describe the
      phenotype of this new experimental animal model after surgically induced hind
      limb ischemia. Plgf-/-, eNos-/-, Plgf-/- eNos-/-, and wild-type C57BL/6J mice
      were studied. Plgf-/- eNos-/- mice showed the most severe phenotype: self
      amputation, and death occurred in up to 47% of the animals studied; in ischemic
      legs, capillary density was severely reduced; macrophage infiltration and
      oxidative stress increased as compared to the other groups of animals. These
      changes were associated with an up-regulation of both inducible NOS (iNOS)
      expression and vascular endothelial growth factor (VEGF) protein levels in
      ischemic limbs, and to an increased extent of protein nitration. Our results
      demonstrate that the deletion of these two genes, Plgf, which acts in synergism
      with VEGF, and eNos, a downstream mediator of VEGF, determines a significant
      change in the vascular response to an ischemic stimulus and that oxidative stress
      within the ischemic tissue represents a crucial factor to maintain tissue
      homeostasis.

PMID- 16608873
TI  - Pax7 and myogenic progression in skeletal muscle satellite cells.
AB  - Skeletal muscle growth and regeneration are attributed to satellite cells -
      muscle stem cells resident beneath the basal lamina that surrounds each myofibre.
      Quiescent satellite cells express the transcription factor Pax7 and when
      activated, coexpress Pax7 with MyoD. Most then proliferate, downregulate Pax7 and
      differentiate. By contrast, others maintain Pax7 but lose MyoD and return to a
      state resembling quiescence. Here we show that Pax7 is able to drive
      transcription in quiescent and activated satellite cells, and continues to do so
      in those cells that subsequently cease proliferation and withdraw from immediate
      differentiation. We found that constitutive expression of Pax7 in satellite-cell
      derived myoblasts did not affect MyoD expression or proliferation. Although
      maintained expression of Pax7 delayed the onset of myogenin expression it did not
      prevent, and was compatible with, myogenic differentiation. Constitutive Pax7
      expression in a Pax7-null C2C12 subclone increased the proportion of cells
      expressing MyoD, showing that Pax7 can act genetically upstream of MyoD. However
      these Pax7-null cells were unable to differentiate into normal myotubes in the
      presence of Pax7. Therefore Pax7 may be involved in maintaining proliferation and
      preventing precocious differentiation, but does not promote quiescence.

PMID- 16608875
TI  - Dynamic microtubules regulate the local concentration of E-cadherin at cell-cell
      contacts.
AB  - In contrast to the well-established relationship between cadherins and the actin
      cytoskeleton, the potential link between cadherins and microtubules (MTs) has
      been less extensively investigated. We now identify a pool of MTs that extend
      radially into cell-cell contacts and are inhibited by manoeuvres that block the
      dynamic activity of MT plus-ends (e.g. in the presence of low concentrations of
      nocodazole and following expression of a CLIP-170 mutant). Blocking dynamic MTs
      perturbed the ability of cells to concentrate and accumulate E-cadherin at cell
      cell contacts, as assessed both by quantitative immunofluorescence microscopy and
      fluorescence recovery after photobleaching (FRAP) analysis, but did not affect
      either transport of E-cadherin to the plasma membrane or the amount of E-cadherin
      expressed at the cell surface. This indicated that dynamic MTs allow cells to
      concentrate E-cadherin at cell-cell contacts by regulating the regional
      distribution of E-cadherin once it reaches the cell surface. Importantly, dynamic
      MTs were necessary for myosin II to accumulate and be activated at cadherin
      adhesive contacts, a mechanism that supports the focal accumulation of E
      cadherin. We propose that this population of MTs represents a novel form of
      cadherin-MT cooperation, where cadherin adhesions recruit dynamic MTs that, in
      turn, support the local concentration of cadherin molecules by regulating myosin
      II activity at cell-cell contacts.

PMID- 16608874
TI  - Lumenal protein sorting to the constitutive secretory pathway of a regulated
      secretory cell.
AB  - Newly synthesized secretory granule content proteins are delivered via the Golgi
      complex for storage within mature granules, whereas constitutive secretory
      proteins are not stored. Most soluble proteins traveling anterograde through the
      trans-Golgi network are not excluded from entering immature secretory granules,
      whether or not they have granule-targeting signals. However, the ;sorting-for
      entry' hypothesis suggests that soluble lumenal proteins lacking signals enter
      transport intermediates for the constitutive secretory pathway. We aimed to
      investigate how these constitutive secretory proteins are sorted. In a pancreatic
      beta-cell line, we stably expressed two lumenal proteins whose normal sorting
      information has been deleted: alkaline phosphatase, truncated to eliminate its
      glycosylphosphatidylinositol membrane anchor (SEAP); and Cab45361, a Golgi
      lumenal resident, truncated to eliminate its intracellular retention (Cab308Myc).
      Both truncated proteins are efficiently secreted, but whereas SEAP enters
      secretory granules, Cab308Myc behaves as a true constitutive marker excluded from
      granules. Interestingly, upon permeabilization of organelle membranes with
      saponin, SEAP is extracted as a soluble protein whereas Cab308Myc remains
      associated with the membrane. These are among the first data to support a model
      in which association with the lumenal aspect of Golgi and/or post-Golgi membranes
      can serve as a means for selective sorting of constitutive secretory proteins.

PMID- 16608876
TI  - The inhibitor-of-apoptosis protein Bir1p protects against apoptosis in S.
      cerevisiae and is a substrate for the yeast homologue of Omi/HtrA2.
AB  - Inhibitor-of-apoptosis proteins (IAPs) play a crucial role in the regulation of
      metazoan apoptosis. IAPs are typically characterized by the presence of one to
      three baculovirus IAP repeat (BIR) domains that are essential for their anti
      apoptotic activity. Bir1p is the sole BIR-protein in yeast and has been shown to
      participate in chromosome segregation events. Here, we show that Bir1p is a
      substrate for Nma111p, which is the homologue of the human pro-apoptotic serine
      protease Omi/HtrA2 and which is known to mediate apoptosis in yeast. Bir1p is a
      cytoplasmic and nuclear protein, and yeast cells lacking bir1 are more sensitive
      to apoptosis induced by oxidative stress. Consistently, overexpression of Bir1p
      reduces apoptosis-like cell death, whereas this protective effect can be
      antagonized in vivo by simultaneous overexpression of Nma111p. Moreover,
      chronologically aged cells that constitutively overexpress Bir1p show a delayed
      onset of cell death. Therefore, Bir1p, like its closest metazoan homologues
      deterin and survivin, has dual functions: it participates in chromosome
      segregation events and cytokinesis and exhibits anti-apoptotic activity.

PMID- 16608877
TI  - Phosphorylation of paracellin-1 at Ser217 by protein kinase A is essential for
      localization in tight junctions.
AB  - Although paracellin-1 (PCLN-1) is known to have a crucial role in the control of
      Mg2+ reabsorption in the kidney, the molecular pathways involved in the
      regulation of PCLN-1 have not been clarified. We used FLAG-tagged PCLN-1 to
      investigate these pathways further, and found that PCLN-1 is phosphorylated at
      Ser217 by protein kinase A (PKA) under physiological conditions in Madin-Darby
      canine kidney (MDCK) cells. PCLN-1 expression decreased Na+ permeability,
      resulting in a decrease in the transepithelial electrical resistance (TER). By
      contrast, PCLN-1 enhanced transepithelial Mg2+ transport. PKA inhibitors, N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89) and
      myristoylated protein kinase A inhibitor 14-22 amide PKI, and an adenylate
      cyclase inhibitor, 2',5'-dideoxy adenosine (DDA), reduced the phosphoserine level
      of PCLN-1. The inhibitory effect of DDA was rescued by 8-bromoadenosine-3',5'
      cyclic monophosphate (8-Br-cAMP). PKA and adenylate cyclase inhibitors decreased
      transepithelial Mg2+ transport and TER. Dephosphorylated PCLN-1 moved from
      detergent-insoluble to soluble fractions and was dissociated from ZO-1. A fusion
      protein of PCLN-1 with glutathione-S-transferase revealed that Ser217 was
      phosphorylated by PKA. Phosphorylated PCLN-1 was localized in the tight junction
      (TJ) along with ZO-1, whereas dephosphorylated PCLN-1 and the S217A mutant were
      translocated into the lysosome. The degradation of dephosphorylated PCLN-1 and
      S217A mutant was inhibited by chloroquine, a specific lysosome inhibitor. Thus,
      the PKA-dependent phosphorylation of Ser217 in PCLN-1 is essential for its
      localization in the TJ and transepithelial Mg2+ transport.

PMID- 16608878
TI  - NIMA-related kinase TbNRKC is involved in basal body separation in Trypanosoma
      brucei.
AB  - The NIMA-related kinase 2 (NEK 2) has important cell cycle functions related to
      centriole integrity and splitting. Trypanosoma brucei does not possess
      centrioles, however, cytokinesis is coupled to basal body separation events. Here
      we report the first functional characterisation of a T. brucei basal body
      cytoskeletal NIMA-related kinase (NRK) protein, TbNRKC. The TbNRKC kinase domain
      has high amino acid identity with the human NEK1 kinase domain (50%) but also
      shares 42% identity with human NEK2. TbNRKC is expressed in bloodstream and
      procyclic cells and functions as a bona fide kinase in vitro. Remarkably, RNAi
      knockdown of TbNRKC and overexpression of kinase-dead TbNRKC in procyclic forms
      induces the accumulation of cells with four basal bodies, whereas overexpression
      of active protein produces supernumary basal bodies and blocks cytokinesis.
      TbNRKC is located on mature and immature basal bodies and is the first T. brucei
      NRK to be found associated with the basal body cytokinesis pathway.

PMID- 16608879
TI  - Caveolin-1 controls cell proliferation and cell death by suppressing expression
      of the inhibitor of apoptosis protein survivin.
AB  - Caveolin-1 is suggested to act as a tumor suppressor. We tested the hypothesis
      that caveolin-1 does so by repression of survivin, an Inhibitor of apoptosis
      protein that regulates cell-cycle progression as well as apoptosis and is
      commonly overexpressed in human cancers. Ectopic expression of caveolin-1 in
      HEK293T and ZR75 cells or siRNA-mediated silencing of caveolin-1 in NIH3T3 cells
      caused downregulation or upregulation of survivin mRNA and protein, respectively.
      Survivin downregulation in HEK293T cells was paralleled by reduced cell
      proliferation, increases in G0-G1 and decreases in G2-M phase of the cell cycle.
      In addition, apoptosis was evident, as judged by several criteria. Importantly,
      expression of green fluorescent protein-survivin in caveolin-1-transfected
      HEK293T cells restored cell proliferation and viability. In addition, expression
      of caveolin-1 inhibited transcriptional activity of a survivin promoter construct
      in a beta-catenin-Tcf/Lef-dependent manner. Furthermore, in HEK293T cells
      caveolin-1 associated with beta-catenin and inhibited Tcf/Lef-dependent
      transcription. Similar results were obtained upon caveolin-1 expression in DLD1
      cells, where APC mutation leads to constitutive activation of beta-catenin
      Tcf/Lef-mediated transcription of survivin. Taken together, these results suggest
      that anti-proliferative and pro-apoptotic properties of caveolin-1 may be
      attributed to reduced survivin expression via a mechanism involving diminished
      beta-catenin-Tcf/Lef-dependent transcription.

PMID- 16608880
TI  - Plectin scaffolds recruit energy-controlling AMP-activated protein kinase (AMPK)
      in differentiated myofibres.
AB  - Plectin, a cytolinker protein greater than 500 kDa in size, has an important role
      as a mechanical stabiliser of cells. It interlinks the various cytoskeletal
      filament systems and anchors intermediate filaments to peripheral junctional
      complexes. In addition, there is increasing evidence that plectin acts as a
      scaffolding platform that controls the spatial and temporal localisation and
      interaction of signaling proteins. In this study we show that, in differentiated
      mouse myotubes, plectin binds to the regulatory gamma1 subunit of AMP-activated
      protein kinase (AMPK), the key regulatory enzyme of energy homeostasis. No
      interaction was observed in undifferentiated myoblasts, and plectin-deficient
      myotubes showed altered positioning of gamma1-AMPK. In addition we found that
      plectin affects the subunit composition of AMPK, because isoform alpha1 of the
      catalytic subunit decreased in proportion to isoform alpha2 during in vitro
      differentiation of plectin(-/-) myotubes. In plectin-deficient myocytes we could
      also detect a higher level of activated (Thr172-phosphorylated) AMPK, compared
      with wild-type cells. Our data suggest a differentiation-dependent association of
      plectin with AMPK, where plectin selectively stabilises alpha1-gamma1 AMPK
      complexes by binding to the gamma1 regulatory subunit. The distinct plectin
      expression patterns in different fibre types combined with its involvement in the
      regulation of isoform compositions of AMPK complexes could provide a mechanism
      whereby cytoarchitecture influences energy homeostasis.

PMID- 16608881
TI  - Matrix metalloproteases from chondrocytes generate an antiangiogenic 16 kDa
      prolactin.
AB  - The 16 kDa N-terminal fragment of prolactin (16K-prolactin) is a potent
      antiangiogenic factor. Here, we demonstrate that matrix metalloproteases (MMPs)
      produced and secreted by chondrocytes generate biologically functional 16K
      prolactin from full-length prolactin. When incubated with human prolactin at
      neutral pH, chondrocyte extracts and conditioned medium, as well as chondrocytes
      in culture, cleaved the Ser155-Leu156 peptide bond in prolactin, yielding - upon
      reduction of intramolecular disulfide bonds - a 16 kDa N-terminal fragment. This
      16K-prolactin inhibited basic fibroblast growth factor (FGF)-induced endothelial
      cell proliferation in vitro. The Ser155-Leu156 site is highly conserved, and both
      human and rat prolactin were cleaved at this site by chondrocytes from either
      species. Conversion of prolactin to 16K-prolactin by chondrocyte lysates was
      completely abolished by the MMP inhibitors EDTA, GM6001 or 1,10-phenanthroline.
      Purified MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13 cleaved human prolactin at
      Gln157, one residue downstream from the chondrocyte protease cleavage site, with
      the following relative potency: MMP-8 > MMP-13 > MMP-3 > MMP-1= MMP-2 > MMP-9.
      Finally, chondrocytes expressed prolactin mRNA (as revealed by RT-PCR) and they
      contained and released antiangiogenic N-terminal 16 kDa prolactin (detected by
      western blot and endothelial cell proliferation). These results suggest that
      several matrix metalloproteases in cartilage generate antiangiogenic 16K
      prolactin from systemically derived or locally produced prolactin.

PMID- 16608882
TI  - Agonist- and depolarization-induced signals for myosin light chain
      phosphorylation and force generation of cultured vascular smooth muscle cells.
AB  - Phosphorylation of myosin light chain (MLC) and contraction of differentiated
      smooth muscle cells in vascular walls are regulated by Ca2+ -dependent activation
      of MLC kinase, and by Rho-kinase- or protein-kinases-C-dependent inhibition of
      MLC phosphatase (MLCP). We examined regulatory pathways for MLC kinase and MLCP
      in cultured vascular smooth muscle cells (VSMCs), and for isometric force
      generation of VSMCs reconstituted in collagen fibers. Protein levels of RhoA, Rho
      kinase and MYPT1 (a regulatory subunit of MLCP) were upregulated in cultured
      VSMCs, whereas a MLCP inhibitor protein, CPI-17, was downregulated. Endothelin-1
      evoked a steady rise in levels of Ca2+, MLC phosphorylation and the contractile
      force of VSMCs, whereas angiotensin-II induced transient signals. Also, Thr853
      phosphorylation of MYPT1 occurred in response to stimuli, but neither agonist
      induced phosphorylation of MYPT1 at Thr696. Unlike fresh aortic tissues, removal
      of Ca2+ or addition of voltage-dependent Ca2+ -channel blocker did not inhibit
      contractions of reconstituted VSMC fibers induced by agonists or even high
      concentrations of extracellular K+ ions. Inhibitors of Ins(1,4,5)P3-receptor and
      Rho-kinase antagonized agonist-induced or high-K+ -induced contraction in both
      reconstituted fibers and fresh tissues. These results indicate that both
      Ins(1,4,5)P3-induced Ca2+ release and Rho-kinase-induced MYPT1 phosphorylation at
      Thr853 play pivotal roles in MLC phosphorylation of cultured VSMCs where either
      Ca2+ -influx or CPI-17-MLCP signaling is downregulated.

PMID- 16608883
TI  - GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological
      concentrations.
AB  - Glucose-dependent insulinotropic polypeptide [GIP-(1-42)] is degraded by
      dipeptidyl peptidase IV (DPP IV), forming GIP-(3-42). In mice, high
      concentrations of synthetic GIP-(3-42) may function as a GIP receptor antagonist,
      but it is unclear whether this occurs at physiological concentrations. In COS-7
      cells transiently transfected with the human GIP receptor, GIP-(1-42) and -(3-42)
      bind with affinities (IC(50)) of 5.2 and 22 nM, respectively. GIP-(1-42) was a
      potent agonist, stimulating cAMP accumulation (EC(50), 13.5 pM); GIP-(3-42) alone
      had no effect. When incubated together with native GIP, GIP-(3-42) behaved as a
      weak antagonist (IC(50), 92 and 731 nM for inhibition of cAMP accumulation
      elicited by 10 pM and 1 nM native GIP, respectively). In the isolated perfused
      rat pancreas, GIP-(3-42) alone had no effect on insulin output and only reduced
      the response to GIP (1 nM) when coinfused in >50-fold molar excess (IC(50), 138
      nM). The ability of GIP-(3-42) to affect the antihyperglycemic or insulinotropic
      actions of GIP-(1-42) was examined in chloralose-anesthetized pigs given
      intravenous glucose. Endogenous DPP IV activity was inhibited to reduce
      degradation of the infused GIP-(1-42), which was infused alone and together with
      GIP-(3-42), at rates sufficient to mimic postprandial concentrations of each
      peptide. Glucose, insulin, and glucagon responses were identical irrespective of
      whether GIP-(1-42) was infused alone or together with GIP-(3-42). We conclude
      that, although GIP-(3-42) can weakly antagonize cAMP accumulation and insulin
      output in vitro, it does not behave as a physiological antagonist in vivo.

PMID- 16608884
TI  - Citrulline modulates muscle protein metabolism in old malnourished rats.
AB  - Protein energy malnutrition is common in the elderly, especially in hospitalized
      patients. The development of strategies designed to correct such malnutrition is
      essential. Our working hypothesis was that poor response to nutrition with
      advancing age might be related to splanchnic sequestration of amino acids, which
      implies that fewer amino acids reach the systemic circulation. Administration of
      citrulline, which is not taken up by the liver, can offer a means of increasing
      whole body nitrogen availability and, hence, improve nutritional status. Thirty
      old (19 mo) rats were submitted to dietary restriction (50% of food intake) for
      12 wk. They were randomized into three groups: 10 rats (R group) were killed and
      20 others refed (90% of food intake) for 1 wk with a standard diet (NEAA group)
      or a citrulline-supplemented diet (Cit group). Before being killed, the rats were
      injected with [(13)C]valine, and the absolute protein synthesis rate (ASR) was
      measured in the tibialis using the flooding-dose method. When the rats were
      killed, the tibialis was removed for protein content analysis. Blood was sampled
      for amino acid and insulin analysis. The standard diet did not have any effect on
      protein synthesis or on the protein content in the muscle. Citrulline
      supplementation led to higher protein synthesis and protein content in muscle
      (117 +/- 9, 120 +/- 14, and 163 +/- 4 mg/organ for protein content in R, NEAA,
      and Cit groups, P < 0.05). The ASR were 0.30 +/- 0.04, 0.31 +/- 0.04, and 0.56 +/
      0.10 mg/h in the three groups, respectively (R and NEAA vs. Cit, P < 0.05).
      Insulinemia was significantly higher in the Cit group. For the first time, a
      realistic therapeutic approach is proposed to improve muscle protein content in
      muscle in frail state related to malnutrition in aging.

PMID- 16608885
TI  - Altered cardiac fatty acid composition and utilization following dexamethasone
      induced insulin resistance.
AB  - Glucocorticoid therapy is often associated with impaired insulin sensitivity and
      cardiovascular disease. The present study was designed to evaluate cardiac fatty
      acid (FA) composition and metabolism following acute dexamethasone (Dex)
      treatment. Using the euglycemic hyperinsulinemic clamp, rats injected with Dex
      demonstrated a reduced glucose infusion rate. This whole body insulin resistance
      was also associated with a heart-specific increase in pyruvate dehydrogenase
      kinase 4 gene expression and a reduction in the rate of glucose oxidation. Dex
      treatment increased basal and postheparin plasma lipolytic activity. In the
      heart, palmitic and oleic acid levels were higher after 4 h of Dex and decreased
      to control (CON) levels within 8 h. Measurement of polyunsaturated FAs
      demonstrated a drop in linoleic and gamma-linolenic acid, with an increase in
      arachidonic acid (AA) after acute Dex injection. Tissue FA can be either oxidized
      or stored as triglyceride (TG). At 4 h, Dex augmented cardiac TG accumulation.
      However, this increase in tissue TG could not be maintained, such that at 8 h
      following Dex, TG declined to CON levels. AMP-activated protein kinase (AMPK)
      activation is known to promote FA oxidation through its control of acetyl-CoA
      carboxylase (ACC). Acute Dex promoted ACC phosphorylation, and increased cardiac
      palmitate oxidation, likely through its effects in increasing AMPK
      phosphorylation and total AMPK protein and gene expression. Whether these acute
      effects of Dex on FA oxidation, TG storage, and arachidonic acid accumulation can
      be translated into increased cardiovascular risk following chronic therapy has
      yet to be determined.

PMID- 16608886
TI  - The effect of an acute elevation of NEFA concentrations on glucagon-stimulated
      hepatic glucose output.
AB  - To determine the effect of nonesterified fatty acids (NEFA) on glucagon action,
      glucagon was infused intraportally (1.65 ng.min(-1).kg(-1)) for 3 h into 18-h
      fasted, pancreatic-clamped conscious dogs in the presence [NEFA + glucagon (GGN)]
      or absence (GGN) of peripheral Intralipid plus heparin infusion. Additionally,
      hyperglycemic (HG), hyperglycemic-hyperlipidemic (NEFA + HG), and glycerol plus
      glucagon (GLYC + GGN) controls were studied. Arterial plasma glucagon
      concentrations rose equally in GGN, NEFA + GGN, and GLYC + GGN but remained basal
      in hyperglycemic controls. Peripheral infusions of Intralipid and heparin
      increased arterial plasma NEFA concentrations equally in NEFA + GGN and NEFA + HG
      and did not change in other protocols. After 15 min, glucagon infusion resulted
      in a rapid, brief increase in net hepatic glycogenolysis (NHGLY, mg.min(-1).kg(
      1)) of approximately 6.0 in GGN and GLYC + GGN but only increased by 3.8 +/- 1.3
      in NEFA + GGN. Thus increases in NHGLY, and consequently net hepatic glucose
      output (NHGO), were blunted by 40%, with no difference between the groups in the
      last 2.5 h of the study. NHGO and NHGLY did not significantly change in HG and
      NEFA + HG. Net hepatic gluconeogenic flux did not change in GGN, GLYC + GGN, or
      HG. However, Intralipid and heparin infusion resulted in similar increases in net
      hepatic gluconeogenic flux in NEFA + GGN and NEFA + HG. Thus elevated NEFA limit
      the initial increase in glucagon-stimulated HGO by blunting glycogenolysis,
      without having any effect on the gluconeogenic or glycogenolytic contributions or
      NHGO thereafter.

PMID- 16608887
TI  - Regression of skeletal manifestations of hyperparathyroidism with oral vitamin D.
AB  - CONTEXT: Parathyroidectomy is the only effective therapy for osteitis fibrosa
      cystica in hyperparathyroidism. OBJECTIVE: The objective of this study was to
      describe the changes of skeletal and nonskeletal manifestations in a patient with
      hyperparathyroidism and renal failure after oral vitamin D therapy. DESIGN: This
      was a descriptive case report. SETTING: The patient was followed up in a referral
      center. PATIENT: A 55-yr-old male patient with moderate renal failure was
      referred for expansile lytic lesions affecting several ribs and the spinous
      process of T12. His creatinine was 1.8 mg/dl; calcium, 8.9 mg/dl; PTH, 666 pg/ml;
      and 1,25 dihydroxy-vitamin D, 27 pg/ml. Bone mineral density (BMD) Z-scores by
      dual-energy x-ray absorptiometry were -4.1 at the spine, -1.7 at the hip, and 
      4.3 at the forearm. MAIN OUTCOME MEASURES: The main outcome measures were the
      skeletal manifestations of hyperparathyroidism. RESULTS: At 10 months of therapy,
      calcium level was 10 mg/d, PTH level declined to 71 pg/ml, and BMD increased by
      12% at the spine and 18% at the hip. Computerized tomography (CT) cuts revealed
      marked regression in the lytic lesions. At 2 yr, BMD increased by an additional
      6% at the spine, and there were no further changes in the lytic lesions by CT.
      The vitamin D receptor genotype using the restriction enzymes Bsm1, Taq1, and
      Apa1 was Bb, tt, and AA. CONCLUSIONS: We showed regression of severe skeletal
      abnormalities of hyperparathyroidism documented by serial CT images in response
      to oral vitamin D therapy. It is possible that the vitamin D receptor genotype of
      the patient modulated this response.

PMID- 16608888
TI  - Thiazolidinedione use and bone loss in older diabetic adults.
AB  - CONTEXT: Activation of peroxisome proliferator-activated receptor-gamma by
      thiazolidinediones (TZDs) results in lower bone mass in mice. OBJECTIVE: The
      objective of the study was to determine whether TZD use is associated with
      changes in bone mineral density (BMD) in older adults with type 2 diabetes.
      DESIGN: We analyzed 4-yr follow-up data from the Health, Aging, and Body
      Composition observational study. SETTING: The study was conducted in a general
      community. PATIENTS: White and black, physically able men and women, aged 70-79
      yr at baseline with diabetes defined by self-report, use of hypoglycemic
      medication, elevated fasting glucose (>/=126 mg/dl), or elevated 2-h glucose
      tolerance test (>/=200 mg/dl) participated in the study. MAIN OUTCOME MEASURES:
      Whole-body, lumbar spine (derived from whole body), and hip BMD were measured by
      dual-energy x-ray absorptiometry at 2-yr intervals. RESULTS: Of 666 diabetic
      participants, 69 reported TZD use at an annual visit, including troglitazone (n =
      22), pioglitazone (n = 30), and/or rosiglitazone (n = 31). Those with TZD use had
      higher baseline hemoglobin A(1c) and less weight loss over 4 yr but similar
      baseline BMD and weight than others with diabetes. In repeated-measures models
      adjusted for potential confounders associated with TZD use and BMD, each year of
      TZD use was associated with greater bone loss at the whole body [additional loss
      of -0.61% per year; 95% confidence interval (CI) -1.02, -0.21% per year], lumbar
      spine (-1.23% per year; 95% CI -2.06, -0.40% per year), and trochanter (-0.65%
      per year; 95% CI -1.18, -0.12% per year) in women, but not men, with diabetes.
      CONCLUSION: These observational results suggest that TZDs may cause bone loss in
      older women. These results need to be tested in a randomized trial.

PMID- 16608889
TI  - Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge.
AB  - CONTEXT: The aim of this article was to review the clinical presentation,
      pathogenesis, and management of thyrotoxic periodic paralysis (TPP). EVIDENCE
      ACQUISITION: A MEDLINE search was conducted for articles published during the
      last 40 yr based on the key words thyrotoxic periodic paralysis and hypokalemic
      periodic paralysis. A total of 281 primary articles and 168 references of the
      retrieved articles were also reviewed. EVIDENCE SYNTHESIS: TPP is a common
      complication of hyperthyroidism in Asian men but is increasingly seen in Western
      countries. Hypokalemia and muscle paralysis results from a sudden intracellular
      shift of potassium and is not due to potassium deficiency. Clinical features of
      hyperthyroidism in patients with TPP may be subtle. Immediate potassium
      supplementation prevents serious cardiopulmonary complications and may hasten the
      recovery of muscle weakness. Nonselective beta-adrenergic blockers can ameliorate
      and prevent recurrence of the paralytic attacks. This episodic paralysis will
      remit with definitive control of hyperthyroidism. Increased sodium-potassium
      ATPase pump activity and enhanced insulin response in patients with TPP is
      postulated to contribute to the hypokalemia. The genetic predisposition for TPP
      is not entirely clear. Association of polymorphisms of the calcium channel alpha1
      subunit gene with TPP has been noted. CONCLUSIONS: Due to population mobility,
      TPP is increasingly common in Western countries. Early diagnosis and prompt
      treatment prevent life-threatening complications associated with hypokalemia and
      muscle weakness. Assaying of thyroid function in patients with hypokalemic
      paralysis distinguishes TPP from other forms of hypokalemic periodic paralysis.

PMID- 16608890
TI  - Changes in extracellular matrix in subcutaneous small resistance arteries of
      patients with primary aldosteronism.
AB  - CONTEXT AND OBJECTIVE: It has been previously demonstrated that aldosterone may
      possess a strong profibrotic action in vitro and in animal models of genetic or
      experimental hypertension. Our aim was to evaluate whether such a profibrotic
      action is present also in the human microcirculation. DESIGN AND PATIENTS: We
      investigated 13 patients with primary aldosteronism, seven patients with
      essential hypertension, and 10 normotensive controls. All subjects were submitted
      to a biopsy of gluteal sc fat tissue. Small resistance arteries were dissected
      and mounted on an isometric myograph, and the tunica media to internal lumen
      ratio was measured. MAIN OUTCOME MEASURES: The total collagen content within the
      tunica media was detected (Sirius red staining and image analysis), and collagen
      subtypes were evaluated using polarized light microscopy; under this condition
      thicker type I collagen fibers appear orange or red, whereas thinner type III
      collagen fibers are yellow or green. RESULTS: Tunica media to internal lumen
      ratio was significantly increased in primary aldosteronism and in essential
      hypertension compared with normotensive controls. Clinic blood pressure values
      were similar in primary aldosteronism and in essential hypertension, and greater
      than in normotensive controls. Normotensive controls had less total and type III
      collagen (3.23 +/- 0.58 and 1.60 +/- 0.22%, respectively) in respect to the two
      hypertensive groups (P < 0.001). Total collagen and type III vascular collagen
      were significantly greater in primary aldosteronism (total collagen, 8.17 +/-
      1.38%; type III collagen, 6.06 +/- 0.74%; P < 0.05) than in essential
      hypertension (total collagen, 6.84 +/- 1.15%; type III collagen, 5.25 +/- 0.80%).
      CONCLUSIONS: Our results indicate that, in small resistance arteries of patients
      with primary aldosteronism, a pronounced fibrosis may be detected, even more
      evident than in blood-pressure-matched patients with essential hypertension.

PMID- 16608891
TI  - Acquired obesity increases CD68 and tumor necrosis factor-alpha and decreases
      adiponectin gene expression in adipose tissue: a study in monozygotic twins.
AB  - CONTEXT: Both acquired and genetic factors regulate adipose tissue function.
      OBJECTIVE: We determined whether adipose tissue mRNA expression is regulated by
      obesity, independently of genetic effects, by studying monozygotic (MZ) twins.
      DESIGN: Seventeen healthy pairs of MZ twins aged 24-27 yr (body mass index 20.0
      33.9 kg/m(2), intrapair differences in body weight 0.1-24.7 kg), were identified
      from the population-based FinnTwin16 cohort. Body fat percent was determined by
      dual-energy x-ray absorptiometry, sc and intraabdominal fat by magnetic resonance
      imaging, liver fat by proton spectroscopy, and insulin sensitivity by using the
      euglycemic insulin clamp technique. Adipocyte cell size and expression of 10
      genes (real-time PCR) were determined in sc adipose tissue biopsies. Serum levels
      of some of the genes were measured using ELISA. RESULTS: Within MZ twin pairs,
      acquired obesity was significantly related to increased adipocyte size and
      increased adipose tissue mRNA expressions of leptin, TNFalpha and the macrophage
      marker CD68, and decreased mRNA expressions of adiponectin and peroxisome
      proliferator-activated receptor-gamma. Intrapair differences in liver fat
      correlated directly with those in leptin and CD68 expression. CD68 expression and
      serum TNFalpha concentrations were correlated with insulin resistance.
      CONCLUSIONS: Acquired obesity independent of genetic influences is able to
      increase expression of macrophage and inflammatory markers and decrease
      adiponectin expression in adipose tissue.

PMID- 16608893
TI  - Intimal estrogen receptor (ER)beta, but not ERalpha expression, is correlated
      with coronary calcification and atherosclerosis in pre- and postmenopausal women.
AB  - BACKGROUND: Controversy exists over the association of estrogen and
      cardiovascular disease. Estrogen receptors (ERs) alpha and beta are expressed in
      the endothelial cells and vascular smooth muscle cells (VSMCs) of many arteries,
      but the relative importance of ERalpha or ERbeta in mediating the vascular
      response to estrogens is not well defined, particularly in humans. We have shown
      previously that postmenopausal women receiving hormone therapy (HT) had lower
      mean coronary artery calcium, plaque area, and calcium-to-plaque ratio compared
      with untreated women. In this study, we examined coronary artery ERalpha and
      ERbeta expression in pre- and postmenopausal women as a function of plaque area,
      calcium area, calcium-to-plaque ratio, and estrogen status. METHODS: Coronary
      arteries were obtained at autopsy from a total of 55 women: nine premenopausal
      women, 13 postmenopausal women on HT and 33 untreated postmenopausal women (non
      HT). Coronary calcification was quantified by contact microradiography, and
      atherosclerotic plaque area was measured histologically. Coronary artery cross
      sections were immunostained for ERalpha and ERbeta, and the amount of receptors
      was estimated semiquantitatively in each arterial wall layer (intima, adventitia,
      and media). Double immunofluorescence was used to colocalize ERalpha and ERbeta
      with smooth muscle actin, a marker of VSMCs. RESULTS: ERbeta and ERalpha were
      expressed in all artery wall layers, but most avidly in the media (P = 0.001),
      and colocalized with VSMCs. ERbeta expression exceeded ERalpha expression in all
      wall layers (P < 0.001) and was adjacent to areas of calcium deposition. ERbeta
      expression in the intimal layer correlated with calcium content, plaque area, and
      calcium-to-plaque ratio (all P < 0.01) and tended to be greater in non-HT than in
      HT women (P = 0.06). ERalpha expression did not vary significantly among groups,
      nor did it correlate with calcium content, plaque area or calcium-to-plaque
      ratio. Expression of ERalpha but not ERbeta declined with age (P < 0.01) in HT
      women only. Age had no effect on ERalpha or ERbeta expression in non-HT or
      premenopausal women. CONCLUSIONS: ERbeta is the predominant ER in human coronary
      arteries and correlates with coronary calcification, a marker of severe
      atherosclerosis. Increased ERbeta expression is linked to advanced
      atherosclerosis and calcification independent of age or hormone status. Future
      pharmacogenetic studies that target this receptor are needed to confirm
      causality.

PMID- 16608892
TI  - Metabolic factors associated with benign prostatic hyperplasia.
AB  - CONTEXT: Benign prostatic hyperplasia poses a significant public health problem,
      but its etiology remains unclear. Obesity and associated abnormalities in glucose
      homeostasis may play a role in benign prostatic hyperplasia development by
      influencing prostate growth. OBJECTIVE: The objective of this study was to
      determine whether obesity, fasting plasma glucose concentration, and diabetes are
      associated with radiologically determined prostate enlargement, an objective
      measure of benign prostatic hyperplasia. DESIGN: This study was a cross-sectional
      analysis with robust variance estimates to account for multiple measures over
      time in the same individuals. SETTING: This prospective cohort study was composed
      of community volunteers. PATIENTS: Patients studied were 422 adult men enrolled
      in The Baltimore Longitudinal Study of Aging. MAIN OUTCOME MEASUREMENTS: Total
      prostate volume as determined by pelvic magnetic resonance imaging was measured.
      RESULTS: Among 422 participants, 91 (21.6%) had prostate enlargement (defined as
      total prostate volume >/= 40 cc) at first visit. Compared with men of normal
      weight [body mass index (BMI) < 25 kg/m(2)], the age-adjusted odds ratio (OR) for
      prostate enlargement for overweight men (BMI, 25-29.9 kg/m(2)) was 1.41 (95% CI,
      0.84-2.37), for obese men (BMI, 30-34 kg/m(2)) was 1.27 (95% CI, 0.68-2.39), and
      for severely obese men (BMI >/= 35 kg/m(2)) was 3.52 (95% CI, 1.45-8.56) (P =
      0.01). Men with elevated fasting glucose (>110 mg/dl) were more likely to have an
      enlarged prostate than men with normal fasting glucose (</=110 mg/dl) (OR, 2.98;
      95% CI, 1.70-5.23), as were men with a diagnosis of diabetes (OR, 2.25; 95% CI,
      1.23-4.11). CONCLUSIONS: Obesity, elevated fasting plasma glucose, and diabetes
      are risk factors for benign prostatic hyperplasia.

PMID- 16608894
TI  - A hypocalcemic child with a novel activating mutation of the calcium-sensing
      receptor gene: successful treatment with recombinant human parathyroid hormone.
AB  - CONTEXT: Persistent hypercalciuria, with the attendant risk of nephrocalcinosis
      and eventual renal failure, is common in hypoparathyroid patients, especially
      those with activating mutations of the calcium-sensing receptor (CASR) gene,
      being treated with oral calcium and calcitriol. Treatment with replacement PTH
      may be warranted, although this has yet to be evaluated in children. OBJECTIVES:
      The objectives of this study were to identify the cause of the disorder in a
      young hypocalcemic patient and to assess the efficacy of treatment of the patient
      with recombinant human PTH(1-34). SUBJECT: An infant presenting with hypocalcemia
      at 3 wk of age was studied. METHODS: CASR gene mutation analysis was performed on
      genomic DNA of the proband and family members. The patient was treated with twice
      daily administration of recombinant human PTH(1-34) over a 17-month period.
      RESULTS: The proband was heterozygous for a de novo novel missense mutation
      (L727Q), on the border between transmembrane helix 4 and intracellular loop 2 of
      the CASR. When transiently expressed in a human embryonic kidney 293 cell line,
      the mutant receptor demonstrated a significant leftward shift in the
      extracellular calcium/intracellular signaling dose-response curve vs. that for
      the wild-type receptor [EC(50); mutant, 2.59 +/- 0.11 mm (mean +/- se) vs. wild
      type, 3.78 +/- 0.12 mm, P < 0.001]. During treatment with PTH(1-34), the patient
      had no further serious hypocalcemic episodes, and his urinary calcium excretion
      declined remarkably. CONCLUSION: PTH should be evaluated further as a treatment
      of autosomal dominant hypocalcemia in young patients.

PMID- 16608895
TI  - Gonadoblastoma arising in undifferentiated gonadal tissue within dysgenetic
      gonads.
AB  - PURPOSE: The purpose of the study was to define the histological origin of
      gonadoblastomas, allowing the identification of high-risk patients. EXPERIMENTAL
      DESIGN: Sixty paraffin-embedded gonadectomy or gonadal biopsy samples of 43
      patients with gonadal dysgenesis were selected from our archives. We studied the
      morphology and immunohistochemical properties of the germ cells in 40 samples
      without neoplastic transformation and compared these findings with the
      morphological and immunohistochemical characteristics of 20 samples containing
      gonadoblastoma/dysgerminoma. RESULTS: The overall incidence of germ cell tumors
      in our patient series was 35%. In dysgenetic gonads without germ cell neoplasia,
      besides the presence of areas with testicular and/or ovarian differentiation,
      areas of undifferentiated gonadal tissue were identified in 13 of 40 samples
      (32.5%). A subpopulation of germ cells within these undifferentiated areas
      stained positive for octamer binding transcription factor (OCT)3/4, the stem cell
      factor receptor, placental-like alkaline phosphatase, and testis-specific protein
      Y encoded. Gonadoblastoma germ cells display identical staining results.
      Moreover, in gonads containing gonadoblastoma, adjacent to this lesion, areas of
      undifferentiated gonadal tissue with identical immunohistochemical
      characteristics were identified in 10 of 20 samples (50%). No adjacent tissue was
      available in five cases, whereas in the five remaining cases, it consisted of
      streak tissue. In three cases, an accumulation of OCT3/4-positive germ cells in
      the proximity of the malignant lesions was found, suggesting clonal expansion and
      final organization into gonadoblastoma nests. CONCLUSIONS: Based on these
      observations, we hypothesize that gonadoblastomas originate from surviving OCT3/4
      positive germ cells in areas of undifferentiated gonadal tissue within the
      dysgenetic gonad. Supportive evidence was obtained that carcinoma in situ arises
      in regions with testicular differentiation.

PMID- 16608896
TI  - Urine steroid hormone profile analysis in cytochrome P450 oxidoreductase
      deficiency: implication for the backdoor pathway to dihydrotestosterone.
AB  - CONTEXT: Although the "backdoor" pathway to dihydrotestosterone has been
      postulated in the fetal-to-early-infantile period of patients with cytochrome
      P450 oxidoreductase deficiency (PORD), clinical data in support of this pathway
      remain limited. OBJECTIVE: The objective of this study was to obtain clinical
      evidence for the presence of the backdoor pathway in PORD. SETTING: This was a
      collaboration study between laboratories and hospitals. SUBJECTS: Twenty-two
      Japanese patients with molecularly confirmed PORD and 1763 control subjects
      participated in this study. INTERVENTION: Urine steroid profile analysis was
      performed by gas chromatography/mass spectrometry. In five patients and 776
      control subjects, urine samples were obtained before 12 months of age. MAIN
      OUTCOME MEASURE: The main outcome measure was identification of a urine
      steroid(s) indicating the backdoor pathway. RESULTS: In the PORD patients,
      pregnanediol, pregnanetriolone, and pregnanetriol were obviously elevated, and
      the urine steroid ratios reflecting CYP17A1 and CYP21A2 activities were decreased
      throughout the examined ages. Furthermore, etiocholanolone and 11
      hydroxyandrosterone, which should originate almost exclusively from
      androstenedione in the conventional "frontdoor" pathway, were grossly normal or
      somewhat decreased since early infancy, whereas androsterone, which can be
      derived not only from androstenedione and dihydrotestosterone in the conventional
      frontdoor pathway but also from 5alpha-pregnane-3alpha,17alpha-diol-20-one in the
      backdoor pathway, was increased during early infancy and remained grossly normal
      thereafter. Thus, the androsterone to etiocholanolone ratio was increased during
      early infancy and remained grossly normal thereafter. 5alpha-Pregnane
      3alpha,17alpha-diol-20-one was elevated throughout the examined ages.
      CONCLUSIONS: The increased androsterone excretion during early infancy, as
      compared with the etiocholanolone and 11-hydroxyandrosterone excretions in the
      same period, suggests the presence of the backdoor pathway in PORD.

PMID- 16608897
TI  - Chemoembolization for liver metastases from medullary thyroid carcinoma.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a well-differentiated
      neuroendocrine tumor. Distant metastases are the main cause of cancer-related
      death. Systemic chemotherapy produces only rare tumor responses. Somatostatin
      analogs and other available modalities are poorly effective to control symptoms.
      AIMS: The aim of our study was to evaluate the impact of liver transarterial
      chemoembolization (TACE) in MTC patients with predominant and progressive liver
      metastases. PATIENTS AND METHODS: Twelve MTC patients underwent 18 TACE courses
      (mean, 1.5; range, 1-2). Response evaluation criteria in solid tumors were used
      to evaluate tumor responses. Symptomatic responses were defined by more than a
      25% decrease of symptoms intensity. RESULTS: Partial radiological tumor response
      was obtained in five patients (42%) with a median duration of 17 months (mean,
      19; range, 15-28 months), stabilization in five (42%) with a median duration of
      24 months (mean, 24; range, 4-39 months), and progression in the remaining two
      (16%). The five partial tumor responses were observed in the nine patients with
      less than 30% liver involvement. Clinical response was observed in two of the
      five patients with diarrhea. Carcinoembryonic antigen did not appear to be a
      useful marker in this setting. Significant grade 3-4 toxicity was observed in one
      patient who had a major tumor necrosis after TACE. CONCLUSION: TACE should be
      considered for treating MTC patients with progressive and predominant liver
      metastasis, and preferably at an early stage during the course of metastatic
      disease.

PMID- 16608898
TI  - Dissociation of serum dehydroepiandrosterone and dehydroepiandrosterone sulfate
      in septic shock.
AB  - CONTEXT: Dehydroepiandrosterone (DHEA) replacement in sepsis has been advocated
      because of the sepsis-associated decrease in serum DHEA sulfate (DHEAS). However,
      experimental sepsis in rodents leads to down-regulation of DHEA sulfotransferase,
      which inactivates DHEA to DHEAS, theoretically resulting in higher DHEA levels.
      OBJECTIVE: The objective of the study was to test whether serum DHEA and DHEAS
      are dissociated in septic shock and to determine their association with
      circulating cortisol in the context of severity of disease and mortality. DESIGN,
      SETTING, AND PARTICIPANTS: This was a cross-sectional study consisting of 181
      patients with septic shock, 31 patients with acute trauma, and 60 healthy
      controls. MAIN OUTCOME MEASURES: Serum cortisol, DHEA, and DHEAS were measured
      before and 60 min after ACTH stimulation. RESULTS: Serum cortisol was increased
      and DHEAS was decreased in both septic shock and trauma patients (all P < 0.001).
      However, compared with healthy controls, DHEA was significantly increased in
      sepsis but decreased after trauma (all P < 0.001). In sepsis, neither cortisol
      nor DHEA increased significantly after ACTH. Most severely ill patients had
      higher cortisol (P = 0.069) and lower DHEA (P = 0.076) and a significantly higher
      cortisol to DHEA ratio (P = 0.004). Similarly, the cortisol to DHEA ratio was
      significantly increased in nonsurvivors of septic shock (P = 0.026), whereas
      survivors did not differ from controls (P = 0.322). CONCLUSIONS: The observed
      dissociation of DHEA and DHEAS in septic shock contradicts the previous concept
      of sepsis-associated DHEA deficiency. Increased DHEA levels may maintain the
      balance between glucocorticoid- and DHEA-mediated immune and vascular effects.
      However, most severe disease and mortality is associated with an increased
      cortisol to DHEA ratio, which may represent a novel prognostic marker in septic
      shock.

PMID- 16608899
TI  - High plasma resistin level is associated with enhanced highly sensitive C
      reactive protein and leukocytes.
AB  - OBJECTIVES: Resistin is a newly described hormone with a suggested role in
      insulin resistance. In humans, inflammatory cells seem to be the major source of
      resistin. The aim of this study was to find out whether plasma resistin
      concentration associates with carotid artery atherosclerosis and the risk factors
      of atherosclerosis. METHODS: Plasma resistin concentrations were measured in 525
      Finnish middle-aged subjects among our population-based cohort. Intima-media
      thickness was measured from the internal carotid artery, the bifurcation
      enlargement, and the common carotid artery. RESULTS: Among all the subjects, the
      median resistin concentration was 7.07 ng/ml (interquartile range, 5.82-8.84),
      women having higher levels than men (P < 0.001) with median values of 7.56 ng/ml
      (6.18-9.19) and 6.67 ng/ml (5.63-8.31), respectively. Resistin level correlated
      negatively with mean intima-media thickness, internal carotid artery, and common
      carotid artery, but the association did not remain significant after adjustments.
      Plasma resistin concentration was associated positively with leukocytes (P <
      0.001), highly sensitive C-reactive protein (P = 0.009), and IGF binding protein
      1 (P < 0.001), but not with plasma insulin or glucose levels in analysis of
      covariance after adjustments for age, sex, and body mass index. CONCLUSIONS: The
      results imply that inflammatory factors are more important in the determination
      of plasma resistin concentration than plasma insulin or glucose values. Resistin
      is associated with proatherogenic inflammatory markers but not independently with
      early atherosclerosis.

PMID- 16608900
TI  - The insulin gene variable number of tandem repeat: associations and interactions
      with childhood body fat mass and insulin secretion in normal children.
AB  - CONTEXT: Polymorphism at the insulin gene (INS) variable number of tandem repeat
      (VNTR) shows variable associations with childhood body mass index (BMI) in
      different populations. OBJECTIVE: The objective of this study was to observe INS
      VNTR associations with body composition and insulin secretion in children.
      DESIGN: The study was designed as a prospective birth cohort study. PARTICIPANTS:
      A total of 947 children genotyped for the INS VNTR participated. MAIN OUTCOME
      MEASURES: Main outcome measures were whole body dual x-ray emission
      absorptiometry at 9 yr to estimate height-corrected fat mass index (FMI), truncal
      FMI, and fat-free mass, and insulin secretion after oral glucose at 8 yr.
      RESULTS: Homozygous III/III children had higher BMI (P = 0.020), FMI (P = 0.015),
      and truncal FMI (P = 0.022) at 9 yr than class I bearers, but no difference in
      fat-free mass (P = 0.23). Gain in weight sd score between birth and 3 yr was
      associated positively with BMI, FMI, and truncal FMI in class I bearers, but not
      in III/III children (p-interaction with genotype = 0.009-0.066). INS VNTR
      genotype was not associated overall with insulin secretion at 8 yr (P = 0.64),
      but class I bearers showed a stronger positive correlation between insulin
      secretion and BMI at 8 yr (regression coefficient +/- se, 0.26 +/- 0.05; P <
      0.0001) than III/III children (-0.10 +/- 0.07; P = 0.48) (p-interaction = 0.003).
      CONCLUSION: We clarified that the overall association between INS VNTR class
      III/III genotype and larger BMI in this population relates to fat mass, but not
      fat-free mass. In contrast, among the subgroup of children who showed rapid
      infancy weight gain, class I bearers tended to have larger BMI and fat mass than
      III/III children. This genetic interaction could relate to insulin secretion,
      which, in class I bearers, increased more rapidly with overweight and obesity.

PMID- 16608901
TI  - Essential role for cholesterol in the delivery of exogenous antigens to the MHC
      class I-presentation pathway.
AB  - Cross-presentation, which is crucial for the generation of immunity against virus
      infected and tumor cells, requires exogenous antigens to be internalized into
      antigen-presenting cells (APCs) followed by translocation to the cytosol by
      unknown mechanisms. One important entry route for such antigens is
      macropinocytosis. We here describe that cholesterol is essential for cross
      presentation of antigens loaded via macropinocytosis into APCs. Modification of
      antigens by palmitoylation to target antigens to cholesterol-enriched plasma
      membrane domains resulted in a dramatically increased T cell activation. These
      results define cholesterol as an essential factor for cross-presentation and
      suggest that specific modification of antigens to increase their affinity for
      cholesterol may be utilized to enhance immunity.

PMID- 16608902
TI  - Increased TGF-beta, Cbl-b and CTLA-4 levels and immunosuppression in association
      with chronic immune activation.
AB  - In this study we investigated the mechanisms mediating T-cell hyporesponsiveness
      in chronically immune-activated individuals. We analyzed in healthy and
      persistently helminth-infected individuals the relationship between immune
      activation and general T-cell hyporesponsiveness, Th3/regulatory T-cell
      expression, transforming growth factor-beta (TGF-beta) secretion, CTL-associated
      antigen 4 (CTLA-4) levels, Casitas B-cell lymphoma-b (Cbl-b) (a negative
      regulator of T-cell activation) levels and phosphorylation of mitogen-activated
      protein kinases/extracellular signal-regulated kinase (ERK)-1 and -2. We found a
      very significant increase in plasma levels of TGF-beta and intracellular pools of
      CTLA-4 and Cbl-b in association with immune activation, which correlates with
      decreased T-cell responses to anti-CD3 stimulation. We demonstrate that the
      impaired activity of ERK of peripheral T cells in highly immune-activated
      individuals is associated with increased levels of CTLA-4 and Cbl-b.
      Interestingly, in some, but not in all, of these immune-activated individuals,
      induction of Cbl-b intracellular pools occurs by TGF-beta or CTLA-4 stimulation.
      We suggest that the higher levels of CTLA-4 and TGF-beta, both involved in the
      induction of Cbl-b, point at potential mechanisms underlying general and antigen
      specific immune hyporesponsiveness in chronically infected individuals.

PMID- 16608903
TI  - Genetic imprinting during impaired spermatogenesis.
AB  - Disorders in genetic imprinting are discussed as potential genetic risk in
      assisted reproduction technology (ART), where most of the natural selection
      mechanisms are bypassed. As currently only limited information about genomic
      imprinting in disruptive spermatogenesis is available, we analysed the imprinting
      state of the paternally methylated gene H19 in various germ cell populations
      derived from seminiferous tubules exhibiting impaired spermatogenesis. Different
      germ cell types were isolated by laser microdissection from human testicular
      paraffin sections. Although the methylation state of the maternally imprinted
      gene SNRPN was investigated by methylation-specific PCR (M-PCR) to establish the
      isolation method, methylation of H19 was analysed by a single-strand conformation
      based method. Contamination by somatic Sertoli cells was excluded because of
      Sertoli cell-specific vimentin immunohistochemistry before germ cell laser
      microdissection. We demonstrate correct genetic imprints for H19 even in
      spermatogonia selected from seminiferous tubules exhibiting spermatogenic arrest
      at the level of spermatogonia, providing no evidence for incorrect genomic
      imprinting in spermatozoa from infertile men used for ICSI.

PMID- 16608904
TI  - PGD for dystrophin gene deletions using fluorescence in situ hybridization.
AB  - Duchenne muscular dystrophy and Becker muscular dystrophy (DMD and BMD) are
      caused by mutations in the dystrophin gene (Xp21). In two-thirds of DMD/BMD
      cases, the mutation is a large deletion of one or several exons. We have
      established PGD for DMD/BMD using interphase fluorescence in situ hybridization
      (FISH) analysis on single nuclei from blastomeres for the detection of deletions
      of specific exons in the dystrophin gene. We performed PGD for two carrier
      females; one had a deletion of exons 45-50 (DMD), and the other had a deletion of
      exons 45-48 (BMD). An exon 45-specific probe was used in combination with probes
      for the X and Y centromeres. Using this straightforward approach, we can
      distinguish affected and unaffected male embryos as well as carrier female and
      normal female embryos. Three cycles were performed for each patient, which
      resulted in a pregnancy and the birth of a healthy girl. To the best of our
      knowledge, this approach for PGD has not been previously reported. The use of
      interphase FISH is an attractive alternative to sexing or PCR-based mutation
      detection for PGD patients with known deletions of the dystrophin gene.

PMID- 16608905
TI  - A two-step protocol for the detection of rearrangements at the AZFc region on the
      human Y chromosome.
AB  - The AZFc region on the human Y chromosome consists mainly of very long direct and
      inverted repeats and is prone to rearrangement. Although deletion of the entire
      AZFc is found only in subfertile men, duplications and deletions of portions of
      AZFc as well as inversions are quite common and represent major polymorphisms of
      the Y chromosome. Several methods are available to detect these rearrangements,
      and each has its own advantages and limits. We designed a two-step PCR protocol
      to study the polymorphic structure of AZFc. The first PCR determines the copy
      number of the Deleted in Azoospermia (DAZ) genes within AZFc using the autosomal
      DAZ-Like gene as a dosage control, and the results could be verified by dosage
      Southern blot analyses. The second PCR simultaneously detects five sequence
      tagged sites (STSs) that are either present or absent in the various AZFc partial
      deletions. One of the STSs, sY1291, was found to be polymorphic in size due to
      varying lengths of a poly-T stretch. A combination of the DAZ dosage PCR and the
      5-STS multiplex PCR reaction detects most, if not all, deletions and duplications
      at AZFc. It offers a simple and reliable way to screen large populations for AZFc
      rearrangements and study their effects on male fertility.

PMID- 16608906
TI  - Induction of endometriosis in the marmoset monkey (Callithrix jacchus).
AB  - Endometriosis is an estrogen-dependent gynaecological disease associated with
      pain and infertility, which occurs in humans and menstruating primates. In this
      study, the marmoset monkey (Callithrix jacchus), which is a non-menstruating
      primate with high circulating estrogen levels, was used to test firstly the
      hypothesis that endometriosis is based on uterine shedding into the peritoneal
      cavity, secondly to study the pathogenesis of endometriosis due to its estrogenic
      situation. Female marmoset monkeys (n = 29) were exposed to two different
      experimental procedures (non-invasive versus invasive) for intrapelvic placement
      of endometrial cells by uterine flushing over an experimental period of 2-3
      years. First endometriotic foci were detected by colour Doppler ultrasound at the
      bladder, the uterus and the ovaries at the earliest after 4 months of either
      treatments. However, invasive induction was more effective in terms of the time
      course of induction and the number of resulting endometriotic foci. The analysis
      of the endometriotic foci by histology, immunohistochemistry and molecular
      techniques allowed a division into two distinct groups: an initial developing
      stage occurred, which under further treatment led to the second stage of
      established endometriosis. Both procedures showed a treatment-dependent increase
      of vascular supply to the endometriotic foci over the experimental period. The
      invasive method induced the final established stage of endometriosis more
      rapidly, with the expression of steroid receptors, aromatase, 17betaHSD1 and
      CD10. Altogether, 72% of the treated marmoset monkeys developed endometriosis
      under our endometrial reflux protocols. Our data support the theory that
      endometriosis can be induced artificially in a non-menstruating primate (C.
      jacchus) by endometrial shedding into the peritoneal cavity. Because the marmoset
      is a primate with very high peripheral estrogen levels, this offers an
      interesting model for studying the pathogenesis of this estrogen-dependent
      disease, as well as for therapeutic impacts on enzymes involved in steroid
      metabolism.

PMID- 16608907
TI  - Comment: Proton pump inhibitor formulary considerations in the acutely ill. Part
      1: pharmacology, pharmacodynamics, and available formulations.

PMID- 16608908
TI  - Sex difference in the antiplatelet effect of aspirin in patients with stroke.
AB  - BACKGROUND: There is substantial interpatient variability in response to aspirin
      after an ischemic stroke or transient ischemic attack (TIA), as assessed by ex
      vivo effects of aspirin on platelet aggregation. The factors contributing to this
      variability are not well defined. OBJECTIVE: To determine whether demographic,
      social, or clinical characteristics are associated with ex vivo response to
      aspirin in patients with a history of stroke or TIA. METHODS: Eighty-one patients
      who were taking aspirin for secondary stroke prevention and underwent ex vivo
      platelet aggregation studies were identified. The medical records of eligible
      patients were reviewed by clinicians who specialize in the management of stroke
      patients. Characteristics were compared between 45 patients who had a complete
      response to aspirin and 36 patients who exhibited an incomplete (partial)
      response to aspirin based on the results of platelet aggregation testing.
      RESULTS: The median (range) aspirin dose was similar in complete (325; 81-1950
      mg/day) and partial (325; 81-1300 mg/day) responders. There was no association
      between aspirin response and age, race, body mass index, medical history, smoking
      status, or use of statin or hormone replacement therapy. However, sex was
      significantly associated with response to aspirin, with more women in the partial
      versus complete responder group (75% vs 49%; p = 0.02). CONCLUSIONS: Our data
      suggest that aspirin may be less effective at inhibiting platelet aggregation in
      women compared with men who have a history of ischemic stroke or TIA.

PMID- 16608910
TI  - Translocation of molecules into cells by pH-dependent insertion of a
      transmembrane helix.
AB  - We have previously observed the spontaneous, pH-dependent insertion of a water
      soluble peptide to form a helix across lipid bilayers [Hunt, J. F., Rath, P.,
      Rothschild, K. J. & Engelman, D. M. (1997) Biochemistry 36, 15177-15192]. We now
      use a related peptide, pH (low) insertion peptide, to translocate cargo molecules
      attached to its C terminus across the plasma membranes of living cells.
      Translocation is selective for low pH, and various types of cargo molecules
      attached by disulfides can be released by reduction in the cytoplasm, including
      peptide nucleic acids, a cyclic peptide (phalloidin), and organic compounds.
      Because a high extracellular acidity is characteristic of a variety of
      pathological conditions (such as tumors, infarcts, stroke-afflicted tissue,
      atherosclerotic lesions, sites of inflammation or infection, or damaged tissue
      resulting from trauma) or might be created artificially, pH (low) insertion
      peptide may prove a useful tool for selective delivery of agents for drug
      therapy, diagnostic imaging, genetic control, or cell regulation.

PMID- 16608911
TI  - Direct evolution of genetic robustness in microRNA.
AB  - Genetic robustness, the invariance of the phenotype in the face of genetic
      perturbations, can endow the organism with reduced susceptibility to mutations. A
      large body of work in recent years has focused on the origins, mechanisms, and
      consequences of robustness in a wide range of biological systems. Despite the
      apparent prevalence of mutational robustness in nature, however, its evolutionary
      origins are still unclear. Does robustness evolve directly by natural selection
      or is it merely a correlated byproduct of other phenotypic traits? By examining
      microRNA (miRNA) genes of several eukaryotic species, we show that the structure
      of miRNA precursor stem-loops exhibits a significantly high level of mutational
      robustness in comparison with random RNA sequences with similar stem-loop
      structures. Hence, this excess robustness of miRNA goes beyond the intrinsic
      robustness of the stem-loop hairpin structure. Furthermore, we show that it is
      not the byproduct of a base composition bias or of thermodynamic stability. These
      findings suggest that the excess robustness of miRNA stem-loops is the result of
      direct evolutionary pressure toward increased robustness. We further demonstrate
      that this adaptive robustness evolves to compensate for structures with low
      intrinsic robustness.

PMID- 16608913
TI  - Persistence of spatial populations depends on returning home.
AB  - There is a need for better description and heuristic understanding of the
      sustainability of populations connected over space by a dispersing stage, both
      for management purposes and to increase our basic knowledge of the dynamics of
      these populations. We show that persistence of such a population of connected
      subpopulations depends on whether the sum of the reproductive gains through all
      possible closed, between-patch reproductive paths through multiple generations,
      relative to the shortfall in self-persistence in each path, exceeds unity plus
      extra terms, which only appear if there are four or more patches. These extra
      terms have the heuristic explanation that they avoid double counting of
      reproductive paths that arise with four or more patches because there can be
      nonoverlapping subnetworks. Thus only those patterns of reproduction and
      connectivity which eventually lead to descendants returning to the patch from
      which they originate contribute to persistence. This result provides the basis
      for evaluating connectivity and habitat heterogeneity to understand reserve
      design, the effects of human fragmentation, the collapse of marine fisheries, and
      other conservation issues.

PMID- 16608912
TI  - Methyl binding domain protein 2 mediates gamma-globin gene silencing in adult
      human betaYAC transgenic mice.
AB  - The genes of the vertebrate beta-globin locus undergo a switch in expression
      during erythroid development whereby embryonic/fetal genes of the cluster are
      sequentially silenced and adult genes are activated. We describe here a role for
      DNA methylation and MBD2 in the silencing of the human fetal gamma-globin gene.
      The gamma-globin gene is reactivated upon treatment with the DNA
      methyltransferase inhibitor 5-azacytidine in the context of a mouse containing
      the entire human beta-globin locus as a yeast artificial chromosome (betaYAC)
      transgene. To elucidate the mechanism through which DNA methylation represses the
      gamma-globin gene in adult erythroid cells, betaYAC/MBD2-/- mice were generated
      by breeding betaYAC mice with MBD2-/- mice. Adult betaYAC/MBD2-/- mice continue
      to express the gamma-globin gene at a level commensurate with 5-azacytidine
      treatment, 10- to 20-fold over that observed with 1-acetyl-2-phenylhydrazine
      treatment alone. In addition, the level of gamma-globin expression is
      consistently higher in MBD2-/- mice in 14.5- and 16.5-days postcoitus fetal liver
      erythroblasts suggesting a role for MBD2 in embryonic/fetal erythroid
      development. DNA methylation levels are modestly decreased in MBD2-/- mice. MBD2
      does not bind to the gamma-globin promoter region to maintain gamma-globin
      silencing. Finally, treatment of MBD2-null mice with 5-azacytidine induces only a
      small, nonadditive induction of gamma-globin mRNA, signifying that DNA
      methylation acts primarily through MBD2 to maintain gamma-globin suppression in
      adult erythroid cells.

PMID- 16608914
TI  - Identification of disialic acid-containing glycoproteins in mouse serum: a novel
      modification of immunoglobulin light chains, vitronectin, and plasminogen.
AB  - Serum glycoproteins are involved in various biologic activities, such as the
      removal of exogenous antigens, fibrinolysis, and metal transport. Some of them
      are also useful markers of inflammation and disease. Although the amount of
      sialic acid increases following inflammation, little attention has been paid to
      the presence of linkage-specific epitopes in serum, especially the alpha2,8
      linkage. In a previous study, we demonstrated that four components in mouse serum
      contain alpha2,8-linked disialic acid (diSia), based on immunoreactivity with
      monoclonal antibody 2-4B, which is specific to N-glycolylneuraminic acid
      (Neu5Gc)alpha2-->(8Neu5Gc alpha2-->)(n-1), n > or = 2 [Yasukawa et al., (2005)
      Glycobiology, 15, 827-837]. In this study, we purified three components, 30-, 70
      , and 120-kDa gp, and identified them as an immunoglobulin (Ig) light chain,
      vitronectin, and plasminogen, respectively, using matrix-assisted laser
      desorption/ionization time-of-flight mass spectroscopy analyses. Modifications of
      these proteins with alpha2,8-linked diSia were chemically confirmed by
      fluorometric C7/C9 analyses and mild acid hydrolysates-fluorometric anion
      exchange chromatography analyses. We also demonstrated that the IgG, IgM, and IgE
      light chains are commonly modified with alpha2,8-linked diSia. In addition, both
      mouse and rat vitronectin contained diSia, and the amount of disialylation in
      vitronectin dramatically decreased after hepatectomy. These results indicate that
      a novel diSia modification of serum glycoproteins is biologically important for
      immunologic events and fibrinolysis.

PMID- 16608915
TI  - The emerging cardioinhibitory role of the hippocampal cholinergic
      neurostimulating peptide.
AB  - Hippocampal cholinergic neurostimulating peptide (HCNP), which derives from
      phosphatidylethanolamine-binding protein (also named Raf kinase inhibitor
      protein), enhances acetylcholine synthesis in the hippocampal medial septal
      nuclei. It is present in the chromaffin secretory granules of the adrenal cells
      and under stress is cosecreted with peptide hormones and catecholamines. Using
      the isolated rat heart perfused according to Langendorff to reveal the
      cardiotropic action of HCNP on the mammalian heart, we showed that rat HCNP
      exerts, at concentrations of 5x10(-13) to 10(-6) M, a negative inotropism under
      basal conditions (left ventricular pressure variations ranging from -8.34+/-0.94%
      to -21+/-3.5%) and enhances the cholinergic-mediated negative inotropy through
      direct interaction with G-protein-coupled muscarinic receptor pathway. Under
      adrenergic stimulation (isoproterenol), the peptide exerts an antiadrenergic
      action. The analysis of the percentage of rate pressure product variations in
      terms of EC50 values of isoproterenol alone (-8.5+/-0.3; r2=0.90) and in the
      presence of rat HCNP at 0.01 nM (-6.9+/-0.36; r2=0.88) revealed a competitive
      type of antagonism of the peptide. HCNP does not affect either heart rate or
      coronary pressure. The evidence that HCNP in mammals may play a novel role as an
      inhibitory cardiac modulator throughout an involvement of the myocardial G
      protein-coupled receptor pathway provides new insights regarding the neurohumoral
      control of heart function under normal and physiopathological conditions.

PMID- 16608916
TI  - Biphenyl-indanone A, a positive allosteric modulator of the metabotropic
      glutamate receptor subtype 2, has antipsychotic- and anxiolytic-like effects in
      mice.
AB  - Previous studies indicate that agonists of the group II metabotropic glutamate
      receptors (mGluRs), mGluR2 and mGluR3, may provide a novel approach for the
      treatment of anxiety disorders and schizophrenia. However, the relative
      contributions of the mGluR2 and mGluR3 subtypes to the effects of the group II
      mGluR agonists remain unclear. In the present study, we describe an alternate
      synthesis and further pharmacological characterization of a recently reported
      positive allosteric modulator of mGluR2 termed biphenyl-indanone A (BINA). In
      recombinant systems, BINA produced a robust and selective potentiation of the
      response of mGluR2 to glutamate with no effect on the glutamate response of other
      mGluR subtypes. In hippocampal brain slices, BINA (1 microM) significantly
      potentiated the mGluR2/3 agonist-induced inhibition of excitatory synaptic
      transmission at the medial perforant path-dentate gyrus synapse. BINA was also
      efficacious in several models predictive of antipsychotic- and anxiolytic-like
      activity in mice. The behavioral effects of BINA were blocked by the mGluR2/3
      antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)
      propanoic acid (LY341495), suggesting that the in vivo effects of BINA are
      mediated by increased activation of mGluR2. Collectively, these results indicate
      that BINA is a selective mGluR2 positive allosteric modulator and provide further
      support for the growing evidence that selective allosteric potentiators of mGluR2
      mimic many of the in vivo actions of mGluR2/3 agonists that may predict
      therapeutic utility of these compounds.

PMID- 16608917
TI  - Interaction of functionalized superparamagnetic iron oxide nanoparticles with
      brain structures.
AB  - Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) combined with magnetic
      resonance imaging (MRI) are under clinical evaluation to enhance detection of
      neurodegenerative diseases. A major improvement would be to link therapeutic
      drugs to the SPIONs to achieve targeted drug delivery, either at the cell surface
      or intracellularly, together with active disease detection, without inducing cell
      reaction. Our objectives were to define the characteristics of SPIONS able to
      achieve cell-specific interaction with brain-derived structures. Our system
      consisted in an iron oxide core (9-10 nm diameter) coated either with dextran
      (Sinerem and Endorem) or various functionalized polyvinyl alcohols (PVAs) (PVA
      SPIONs). We investigated the cellular uptake, cytotoxicity, and interaction of
      these various nanoparticles with brain-derived endothelial cells, microglial
      cells, and differentiating three-dimensional aggregates. None of the
      nanoparticles coated with dextran or the various PVAs was cytotoxic or induced
      the production of the inflammatory mediator NO used as a reporter for cell
      activation. AminoPVA-SPIONs were taken up by isolated brain-derived endothelial
      and microglial cells at a much higher level than the other SPIONs, and no
      inflammatory activation of these cells was observed. AminoPVA-SPIONs did not
      invade brain cells aggregates lower than the first cell layer and did not induce
      inflammatory reaction in the aggregates. Fluorescent aminoPVA-SPIONs derivatized
      with a fluorescent reporter molecule and confocal microscopy demonstrated
      intracellular uptake by microglial cells. Fluorescent aminoPVA-SPIONs were well
      tolerated by mice. Therefore, functionalized aminoPVA-SPIONs represent
      biocompatible potential vector systems for drug delivery to the brain that may be
      combined with MRI detection of active lesions in neurodegenerative diseases.

PMID- 16608918
TI  - Phosducin and phosducin-like protein attenuate G-protein-coupled receptor
      mediated inhibition of voltage-gated calcium channels in rat sympathetic neurons.
AB  - Phosducin (PDC) has been shown in structural and biochemical experiments to bind
      the Gbetagamma subunit of heterotrimeric G-proteins. A proposed function of PDC
      and phosducin-like protein (PDCL) is the sequestration of "free" Gbetagamma from
      the plasma membrane, thereby terminating signaling by Gbetagamma. The functional
      impact of heterologously expressed PDC and PDCL on N-type calcium channel
      (CaV2.2) modulation was examined in sympathetic neurons, isolated from rat
      superior cervical ganglia, using whole-cell voltage clamp. Expression of PDC and
      PDCL attenuated voltage-dependent inhibition of N-type calcium channels, a
      Gbetagamma-dependent process, in a time-dependent fashion. Calcium current
      inhibition after short-term exposure to norepinephrine was minimally altered by
      PDC or PDCL expression. However, in the continued presence of norepinephrine, PDC
      or PDCL relieved calcium channel inhibition compared with control neurons. We
      observed similar results after activation of heterologously expressed
      metabotropic glutamate receptors with 100 microM L-glutamate. Neurons expressing
      PDC or PDCL maintained suppression of inhibition after re-exposure to agonist.
      Unlike other Gbetagamma sequestering proteins that abolish the short-term
      inhibition of Ca2+ channels, PDC and PDCL require prolonged agonist exposure
      before effects on modulation are realized.

PMID- 16608919
TI  - Functional validation of the genetic polymorphisms of human ATP-binding cassette
      (ABC) transporter ABCG2: identification of alleles that are defective in
      porphyrin transport.
AB  - The ATP-binding cassette (ABC) transporter ABCG2 has been implicated to play a
      significant role in the response of patients to medication and/or the risk of
      diseases. To clarify the possible physiological or pathological relevance of
      ABCG2 polymorphisms, we have functionally validated single nucleotide
      polymorphisms (SNP) of ABCG2. In the present study, based on the currently
      available data on SNPs and acquired mutations, we have created a total of 18
      variant forms of ABCG2 (V12M, G51C, Q126stop, Q141K, T153M, Q166E, I206L, F208S,
      S248P, E334stop, F431L, S441N, R482G, R482T, F489L, F571I, N590Y, and D620N) by
      site-directed mutagenesis and expressed them in insect cells. Because porphyrins
      are considered to be endogenous substrates for ABCG2, we have investigated the
      porphyrin transport activity of those variant forms in vitro. We herein provide
      evidence that the variants Q126stop, F208S, S248P, E334stop, and S441N are
      defective in porphyrin transport, whereas F489L exhibited impaired transport,
      approximately 10% of the activity observed for the wild type. Furthermore, Flp-In
      293 cells expressing those variants were photosensitive. Thus, among those
      genetic polymorphisms of ABCG2, at least the hitherto validated alleles of
      Q126stop, S441N, and F489L are suggested to be of clinical importance related to
      the potential risk of porphyria.

PMID- 16608920
TI  - Ketoconazole and miconazole are antagonists of the human glucocorticoid receptor:
      consequences on the expression and function of the constitutive androstane
      receptor and the pregnane X receptor.
AB  - The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) play
      a major part in the control of drug metabolism and transport. We have previously
      shown that PXR and CAR expression is controlled by the glucocorticoid receptor
      (GR) and proposed the existence of a signal transmission cascade GR-(PXR/CAR)
      drug metabolizing and transporter systems. In the current study, we investigated
      the effect of ketoconazole and other azole-derived drugs, miconazole and
      fluconazole, on the transcriptional activity of the human GR (hGR) in HeLa and
      HepG2 cells, and in primary human hepatocytes. The data show that ketoconazole
      inhibits GR transcriptional activity and competes with dexamethasone for hGR
      binding. In primary human hepatocytes, ketoconazole inhibits the expression of 1)
      GR-responsive genes tyrosine aminotransferase and both PXR and CAR; 2) CAR and
      PXR target genes, including cytochromes P450 (P450) CYP2B6, CYP2C9, and CYP3A4;
      UDP-glucuronosyltransferase 1A1, glutathione S-transferases A1 and A2; and
      transporter proteins (phase III) solute carrier family 21 form A6 and multidrug
      resistance protein 2. In parallel experiments, ketoconazole affected neither the
      expression of GR, the expression of glyceraldehyde-3-phosphate dehydrogenase, nor
      the inducible expression of CYP1A1 and 1A2. Miconazole behaved like ketoconazole,
      whereas fluconazole had no effect. We conclude that, in addition to their well
      known inhibitory effect on P450 enzyme activities, ketoconazole and miconazole
      are antagonists of hGR. These results provide a novel molecular mechanism by
      which these compounds may exert adverse and toxic effects on drug metabolism and
      other functions in human.

PMID- 16608921
TI  - The promoter region of the MDR1 gene is largely invariant, but different single
      nucleotide polymorphism haplotypes affect MDR1 promoter activity differently in
      different cell lines.
AB  - The MDR1 multidrug transporter represents one of the better characterized drug
      transporters that play an important role in protecting the body against
      xenobiotic insults. Single nucleotide polymorphisms (SNPs) and SNP haplotypes
      within this gene have been variously associated with differences in MDR1
      expression/function, drug response as well as disease susceptibility.
      Nonetheless, the effect of polymorphisms at the MDR1 promoter region on its
      promoter activity remains less characterized. Through the examination of
      approximately 1.5 kilobases of MDR1 promoter region from five populations,
      including the Chinese, Malays, Indians, European Americans, and African
      Americans, we identified eight low-frequency SNPs, of which only two were
      polymorphic in at least four of the five populations examined. The other SNPs are
      mainly population-specific, the majority of which occur only in the African
      American population. Recapitulation of the various combinations of SNP haplotypes
      in vitro in promoter-reporter assays revealed a few notable trends. The African
      and European American-specific haplotypes tended to result in enhanced MDR1
      promoter activity only in the human embryonic kidney (HEK) 293 cell line.
      Haplotype GCTAACC, which occurs at variable frequencies in all the populations
      examined, with Asians having much lower frequencies (<2%) compared with the
      European Americans/African Americans (>4%), affected MDR1 promoter activity
      differently in different cell lines. Compared with the commonest haplotype, GCTA
      ACC haplotype resulted in a significant decrease in MDR1 promoter activity in
      HeLa cells (P < 0.05) but a significant increase in the same promoter activity in
      HEK293 cells (P < 0.05). These results suggest that the MDR1 promoter region is
      largely invariant but that different haplotypes have differential effects on the
      MDR1 promoter activity in different cell lines.

PMID- 16608922
TI  - Chemical inducers of rodent glutathione s-transferases down-regulate human GSTA1
      transcription through a mechanism involving variant hepatic nuclear factor 1-C.
AB  - The regulation of human GSTA1 by chemical inducers of rodent glutathione S
      transferases (GSTs) and the regulatory role of hepatic nuclear factor (HNF) 1 was
      investigated in Caco-2 cells. Treatment of preconfluent and confluent cells with
      12-O-tetra-decanoyl phorbol-13-acetate (TPA), 3-methylcholanthrene (3-MC), 2-tert
      butyl-4-hydroxy-anisol (BHA), and phenobarbital (PB) reduced GSTA1 mRNA levels in
      preconfluent and confluent cells. Constitutive levels of GSTA1 and HNF1alpha mRNA
      were elevated 6.25- and 50-fold, respectively, in postconfluent cells compared
      with preconfluent cells. Overexpression of HNF1alpha in cells transfected with a
      GSTA1 promoter-luciferase construct (pGSTA1-1591-luc) resulted in dose-related
      increases in reporter activity not observed when an HNF1 response element (HRE)
      in the proximal promoter was mutated (pGSTA1-DeltaHNF1-luc). TPA, 3-MC, BHA, and
      PB reduced HNF1alpha mRNA levels in preconfluent and confluent cells and caused
      marked reductions in luciferase activity in pGSTA1-1591-luc transfectants.
      Transcriptional repression was abrogated with pGSTA1-DeltaHNF1-luc and with
      truncated constructs that eliminated a functional HRE. Moreover, cotransfection
      of pHNF1alpha with pGSTA1-1591-luc partially prevented the reduction in
      luciferase activity by rodent GST inducers. Immunoblot analysis of DNA binding
      studies indicate that variant (v)HNF1-C binding to HRE is increased in
      preconfluent cells treated with 3-MC, BHA, and PB. In addition, overexpression of
      vHNF1-C repressed GSTA1 transcriptional activity in luciferase reporter assays.
      Finally, treatment with 3-MC, BHA, and PB increased vHNF1-C mRNA levels in
      preconfluent cells. These data demonstrate that repression of human GSTA1
      transcription by chemical inducers of rodent GSTs occurs, in part, through a
      mechanism involving the repressive action of vHNF1-C.

PMID- 16608923
TI  - Does screening for COPD by primary care physicians have the potential to cause
      more harm than good?

PMID- 16608924
TI  - Change in the BODE index reflects disease modification in COPD: lessons from lung
      volume reduction surgery.

PMID- 16608925
TI  - Tobacco dependence treatment: time to change the paradigm.

PMID- 16608926
TI  - When pulmonary embolism treatment isn't working.

PMID- 16608927
TI  - Second-line chemotherapy for non-small cell lung cancer.

PMID- 16608928
TI  - Understanding vocal cord dysfunction: a step in the right direction with a long
      road ahead.

PMID- 16608929
TI  - A randomized controlled trial on office spirometry in asthma and COPD in standard
      general practice: data from spirometry in Asthma and COPD: a comparative
      evaluation Italian study.
AB  - STUDY OBJECTIVES: To evaluate whether office spirometry by general practitioners
      (GPs) is feasible and may improve the diagnosis of asthma and COPD. METHODS: A
      prospective, randomized, comparative trial was planned involving 57 Italian
      pulmonology centers and 570 GPs who had to enroll consecutive subjects aged 18 to
      65 years with symptoms of asthma or COPD without a previous diagnosis. Patients
      were randomized 1:1 into two groups with an interactive voice responding system:
      conventional evaluation alone vs conventional evaluation and spirometry. Office
      spirometry was performed by GPs who were trained by reference specialists using a
      portable electronic spirometer (Spirobank Office; MIR; Rome, Italy). Diagnosis
      was confirmed by the reference specialist center in blind fashion. RESULTS:
      Seventy-four GPs complied to the trial. Of 333 patients enrolled, 136 nonrandom
      violators completed the protocol. Per-protocol analysis showed a concordant
      diagnosis between GPs and specialists in 78.6% of cases in the conventional
      evaluation-plus-spirometry group vs 69.2% in the conventional evaluation group (p
      = 0.35). In the intention-to-treat analysis, the respective percentages of
      concordant diagnosis were 57.9 and 56.7 (p = 0.87). CONCLUSIONS: Office
      spirometry by GPs is feasible, but frequent protocol violation and inadequate
      sample size did not allow us to prove a significant advantage of office
      spirometry in improving the diagnosis of asthma and COPD in standard general
      practice as organized at present in Italy, thus reinforcing the need for close
      cooperation between GPs and specialists in respiratory medicine.

PMID- 16608930
TI  - Pulmonary function and abdominal adiposity in the general population.
AB  - BACKGROUND: The prevalence of obesity is increasing, and there is evidence that
      obesity, in particular abdominal obesity as a marker of insulin resistance, is
      negatively associated with pulmonary function. The mechanism for this association
      and the best marker of abdominal adiposity in relation to pulmonary function is
      not known. STUDY OBJECTIVE: We assessed the association between pulmonary
      function and weight, body mass index (BMI), waist circumference, waist/hip ratio,
      and abdominal height as markers of adiposity and body fat distribution. We used
      multiple linear regression to analyze the association of pulmonary function (ie,
      FEV(1) and FVC) [with maneuvers performed in the sitting position] with overall
      adiposity markers (ie, weight and BMI) and abdominal adiposity markers,
      stratified by gender, and adjusted for height, age, race, smoking, and other
      covariates. SETTING AND PARTICIPANTS: A random sample of individuals (n = 2,153)
      from the general population living in western New York state, 35 to 79 years of
      age. RESULTS: In women, abdominal height and waist circumference were negatively
      associated with FEV(1) percent predicted, while all five adiposity markers were
      negatively associated with FVC percent predicted. In men, all overall and
      abdominal adiposity markers were inversely associated with FEV(1) percent
      predicted and FVC percent predicted. CONCLUSION: These results suggest that
      abdominal adiposity is a better predictor of pulmonary function than weight or
      BMI, and investigators should consider it when investigating the determinants of
      pulmonary function.

PMID- 16608931
TI  - Effect of lung resection on exercise capacity and on carbon monoxide diffusing
      capacity during exercise.
AB  - OBJECTIVE: To evaluate the effect of lung resection on lung function and exercise
      capacity values, including diffusion capacity of the lung for carbon monoxide
      (Dlco), during exercise, and to determine whether postoperative lung function,
      including exercise capacity and Dlco during exercise, could be predicted from
      preoperative lung function and the number of functional segments resected.
      DESIGN: Prospective study. SETTING: Clinical pulmonary function laboratory in a
      university teaching hospital. PATIENTS: Twenty-eight patients undergoing lung
      resection at Vancouver General Hospital from October 1998 to May 1999, were
      studied preoperatively and 1-year postoperatively. INTERVENTIONS: We determined
      FEV(1) and FVC, and maximal oxygen uptake (Vo(2)max) and maximal workload (Wmax)
      achieved during incremental exercise testing. We used the three-equation
      modification of the single-breath Dlco technique to determine Dlco at rest
      (RDlco) and during steady-state exercise at 70% of Wmax, and the increase in Dlco
      from rest to exercise (ie, the mean increase in Dlco percent predicted at 70% of
      Wmax from resting Dlco percent predicted [(70%-R)Dlco]). We calculated the
      predicted postoperative (PPO) values for all the above parameters using the
      preoperative test data and the extent of functioning bronchopulmonary segments
      resected, and compared the results with the actual 1-year postoperative results.
      RESULTS: Following lung resection, there was a significant reduction in FEV(1),
      FVC, and Dlco with decreases of 12%, 13%, and 22% predicted, respectively. There
      were also significant decreases in Vo(2)max per kilogram of 2.1 mL/min/kg (8% of
      predicted Vo(2)max) and in Wmax of 12 W (7% of predicted Wmax). However, (70%
      R)Dlco did not significantly decrease after lobectomy but decreased after
      pneumonectomy. The calculated PPO values significantly underestimated
      postoperative values after pneumonectomy but were acceptable for lobectomy.
      CONCLUSIONS: Exercise tests may be better indicators of functional capacity after
      lung resection than measurements of FEV(1) and FVC or RDlco. PPO results
      calculated by estimating the functional contribution of the resected segments,
      are comparable with those obtained using ventilation-perfusion lung scanning and
      significantly underestimate postoperative lung function after pneumonectomy, but
      are acceptable for lobectomy.

PMID- 16608932
TI  - The BODE index after lung volume reduction surgery correlates with survival.
AB  - STUDY OBJECTIVE: A recently introduced, multidimensional index called BODE (body
      mass index [BMI], degree of airflow obstruction assessed by spirometry, grade of
      dyspnea, and exercise capacity), quantified by 6-min walking distance (6MWD), has
      excellent predictive power with respect to outcome in COPD. We investigated
      whether the BODE index is able to predict survival after lung volume reduction
      surgery (LVRS). DESIGN: Retrospective study. SETTING: Tertiary university
      hospital. PATIENTS: One hundred eight-six COPD patients (76 women) with severe
      emphysema (mean +/- SD age, 64 +/- 8 years; mean FEV(1), 28 +/- 8% of predicted).
      INTERVENTION: Bilateral thoracoscopic LVRS. MEASUREMENTS AND RESULTS: BMI,
      pulmonary function, 6MWD, and the modified Medical Research Council dyspnea score
      were assessed before and 3 months after LVRS, and the BODE index was calculated.
      The patients were followed up with respect to survival for a median time of 40
      months (range, 3 to 116 months) after surgery. The mean BODE index decreased from
      7.2 +/- 1.6 preoperatively to 4.0 +/- 2.0 at 3 months after LVRS (p < 0.001). The
      postoperative but not the preoperative BODE correlated with survival, although
      preoperative patient characteristics were comparable between short-term (< 5
      years) and long-term (> 5 years) survivors. A decrease to a lower BODE score
      class was associated with a reduced mortality (hazard ratio, 0.497, 95%
      confidence interval, 0.375 to 0.659; p < 0.001). The C statistic for the ability
      of the BODE index to predict the risk of death was larger (0.74) than that for
      the FEV(1) (0.63), the degree of dyspnea (0.64), or the 6MWD (0.62). CONCLUSIONS:
      The postoperative BODE index is a powerful predictor of survival in COPD patients
      after LVRS.

PMID- 16608933
TI  - Seven-year cumulative incidence of COPD in an age-stratified general population
      sample.
AB  - AIM: To estimate the cumulative incidence of COPD and risk factors related to the
      development of COPD, including evaluation of the relationship between Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) stage 0 (ie, respiratory
      symptoms and normal lung function) and the development of COPD, in an age
      stratified general population sample of middle-aged and elderly individuals.
      METHOD: The third survey of the Obstructive Lung Disease in Northern Sweden
      studies cohort I (three age strata born in 1919 to 1920, 1934 to 1935, and 1949
      to 1950) was performed in 1996, and 5,189 subjects (88%) responded to the postal
      questionnaire. Of the responders, a random sample (1,500 subjects) was invited to
      an examination in 1996 and in 2003. A total of 963 subjects performed spirometry
      on both occasions. COPD was defined according to the spirometric criteria of the
      GOLD. Two levels of disease severity, grade I and higher (GOLD criteria,
      FEV(1)/FVC ratio of < 0.70) and also grade II and higher (GOLD II criteria,
      FEV(1)/FVC ratio of < 0.70 and FEV(1) <80% predicted). RESULTS: The 7-year
      cumulative incidence of COPD was 11.0% and 4.9%, respectively, according to GOLD
      and GOLD II, and was significantly related to smoking (smokers, 18.8% and 10.6%,
      respectively; ex-smokers, 10.5% and 5.2%, respectively; non-smokers, 7.6% and
      1.6%, respectively). Incident COPD according to GOLD, but not according to GOLD
      II, was significantly associated with increasing age. Most respiratory symptoms
      at study entry were markers of increased risk for incident COPD when analyzed in
      a multivariate model adjusting for confounders. CONCLUSION: The GOLD criteria
      yielded a higher cumulative incidence (11.0%) compared to the GOLD II (4.9%).
      Smoking, but not gender, was associated with incident COPD. Most respiratory
      symptoms at the beginning of the observation period marked an increased risk for
      developing COPD, thus the classification GOLD stage 0 seems relevant among middle
      aged and elderly persons.

PMID- 16608934
TI  - Exercise performance improves in patients with COPD due to respiratory muscle
      endurance training.
AB  - BACKGROUND: Impaired exercise tolerance is frequently observed in patients with
      COPD. Respiratory muscle endurance training (RMET) by means of normocapnic
      hyperpnea can be used to improve respiratory muscle function and probably
      exercise capacity. RMET is not applied on a large scale because complicated
      equipment is needed to maintain carbon dioxide homeostasis during hyperpnea,
      which can also be done by enlarging the dead space of the ventilatory system by
      breathing through a tube. Therefore, tube breathing might be a new, inexpensive
      method for home-based RMET. The aim of this study was to assess whether home
      based RMET by means of tube breathing improves endurance exercise performance in
      patients with COPD. METHODS: We randomized 36 patients with moderate-to-severe
      COPD to RMET by paced tube breathing (n = 18) or sham training (control, n = 18).
      Both groups trained twice daily for 15 min, 7 days per week, for 5 weeks.
      RESULTS: Patients receiving RMET showed significant improvements in endurance
      exercise capacity (constant-load exercise on cycle ergometry; 18 min vs 28 min, p
      < 0.001), in perception of dyspnea (Borg score; 8.4 vs 5.4, p < 0.001), and
      respiratory muscle endurance capacity (sustainable inspiratory pressure; 25 cm
      H(2)O vs 31 cm H(2)O, p = 0.005). Quality of life (chronic respiratory disease
      questionnaire) also improved (78.7 to 86.6, p = 0.001). The control group showed
      no significant changes. CONCLUSION: Home-based RMET by means of tube breathing
      leads to a significant improvement of endurance exercise capacity, a reduction in
      perception of dyspnea, and an improvement in quality of life in patients with
      moderate-to-severe COPD.

PMID- 16608935
TI  - Airway blood flow reactivity in healthy smokers and in ex-smokers with or without
      COPD.
AB  - STUDY OBJECTIVES: Cigarette smoking has been associated with impaired endothelium
      dependent relaxation responses in the brachial and coronary arteries (endothelial
      dysfunction). The aim of the present study was to determine whether the airway
      circulation is also affected and whether pharmacologic treatment has an effect on
      endothelial function in patients with COPD. METHODS AND PATIENTS: Airway blood
      flow (Qaw) responses to therapy with inhaled albuterol, which causes endothelium
      dependent vasodilation, were measured with a noninvasive soluble-gas-uptake
      technique in age-matched healthy current smokers (n = 10), healthy ex-smokers (n
      = 10), ex-smokers with COPD (n = 10), and healthy lifetime nonsmokers. In the ex
      smokers with COPD, the albuterol responsiveness measurement was repeated after 4
      weeks of treatment with fluticasone/salmeterol and after a drug washout period of
      4 or 8 weeks. RESULTS: The mean (+/- SE) baseline Qaw values ranged between 40.7
      +/- 3.9 and 50.9 +/- 2.8 microL/min/mL anatomic dead space in the four groups
      (differences were not significant). The mean FEV(1) was 53.4 +/- 2.3% predicted
      in the ex-smokers with COPD. Albuterol inhalation increased mean Qaw
      significantly in lifetime nonsmokers (50.1 +/- 8.3% predicted; p < 0.05) and
      healthy ex-smokers (37.2 +/- 3.4% predicted; p < 0.05), but not in healthy
      current smokers (13.9 +/- 3.2% predicted; difference was not significant) and ex
      smokers with COPD (9.7 +/- 4.5% predicted; difference was not significant). While
      fluticasone/salmeterol did not change Qaw significantly, it restored albuterol
      responsiveness (67.6 +/- 11.1% predicted; p < 0.05) in the ex-smokers with COPD;
      this effect was no longer seen after the drug washout period. CONCLUSIONS:
      Cigarette smoking is associated with a blunted vasodilator response to inhaled
      albuterol in the airway as an expression of endothelial dysfunction, with a
      partial recovery of albuterol responsiveness after smoking cessation in healthy
      ex-smokers but not in ex-smokers with COPD. In the latter group, combined
      glucocorticoid/long-acting beta(2)-adrenergic agonist treatment restores
      albuterol responsiveness. The role of endothelial dysfunction in the
      physiopathology of COPD remains to be examined.

PMID- 16608936
TI  - Impact of pulmonary rehabilitation on psychosocial morbidity in patients with
      severe COPD.
AB  - STUDY OBJECTIVE: To assess the effect of pulmonary rehabilitation (PR) on
      psychosocial morbidity, functional exercise capacity, and health-related quality
      of life (HRQL) in patients with severe COPD. DESIGN: A prospective, randomized,
      controlled trial with blinding of outcome assessment and data analysis. SETTING:
      A tertiary-care respiratory service. PATIENTS: Forty patients (mean age, 65 +/- 8
      years [+/- SD]) with severe chronic flow limitation (FEV(1), 35 +/- 13%) without
      respiratory failure (Pao(2), 72 +/- 9 mm Hg; Paco(2), 42 +/- 5 mm Hg) were
      randomized either to a control group or to a PR group (PRG). INTERVENTIONS:
      Sixteen weeks of PR that included breathing retraining and exercise.
      MEASUREMENTS: At baseline and 16 weeks, we evaluated psychosocial morbidity using
      two questionnaires (the Millon Behavior Health Inventory [MBHI] and the Revised
      Symptom Checklist [SCL-90-R]) and measured 6-min walk distance (6WMD) and HRQL
      using the Chronic Respiratory Questionnaire (CRQ). RESULTS: We found differences
      in favor of the PRG in the following MBHI domains: introversive, forceful, and
      sensitive personality styles (all p </= 0.05) and chronic tension (p </= 0.01).
      Results of the depression, hostility, global severity, positive symptom distress
      index (all p </= 0.01), somatization, anxiety, psychoticism, and positive symptom
      (all p </= 0.05) domains of the SCL-90-R favored the PRG. We also found
      statistically and clinically significant differences between groups in 6MWD (85
      m; p < 0.01) and in two domains of the CRQ: dyspnea (1.0; p < 0.01) and mastery
      (0.6; p < 0.05). The other two domains of CRQ showed strong trends in favor of
      PRG: 0.7 for both fatigue and emotional function (minimal important difference,
      0.5). CONCLUSIONS: PR may decrease psychosocial morbidity in COPD patients even
      when no specific psychological intervention is performed. Findings from this
      study also confirm the positive impact of PR on functional exercise capacity and
      HRQL.

PMID- 16608937
TI  - High levels of medical utilization by ambulatory patients with vocal cord
      dysfunction as compared to age- and gender-matched asthmatics.
AB  - STUDY OBJECTIVES: To evaluate medical utilization by ambulatory patients with
      vocal cord dysfunction (VCD). DESIGN: Retrospective, case-control study. SETTING:
      Pulmonary disease clinic at an army tertiary-care center. PATIENTS: Twenty-five
      ambulatory patients with VCD (mean age, 41 years; range, 27 to 69 years) who were
      age- (+/- 3 years) and gender-matched to 25 control patients with moderate
      persistent asthma. MEASUREMENTS AND RESULTS: Medical utilization for the year
      preceding the diagnosis of VCD or asthma was obtained from a computerized medical
      record. End points included total outpatient visits, evaluations by subspecialty
      physicians, presentations for urgent care, hospitalizations, and number of
      prescriptions. Total physician visits (477 visits vs 267 visits, respectively; p
      < 0.004) and subspecialty care visits (277 visits vs 118 visits; p < 0.007) were
      significantly greater among the VCD cohort as compared with the asthmatic cohort.
      The groups were also found to have comparable utilization of prescriptions (448
      prescriptions vs 394 prescriptions, respectively; p < 0.63), frequency of
      hospitalizations (seven hospitalizations vs five hospitalizations; p < 0.59), and
      urgent care visits (45 visits vs 20 visits; p < 0.14). CONCLUSIONS: Ambulatory
      VCD patients use significantly more medical provider resources and similar
      pharmaceutical assets as compared to patients with moderate persistent asthma.

PMID- 16608938
TI  - The Ontario Asthma Regional Variation Study: emergency department visit rates and
      the relation to hospitalization rates.
AB  - BACKGROUND: Hospitalization rates for asthma vary more than threefold across
      regions of Ontario. It is not known whether this variation is primarily due to
      regional differences in the rate of emergency department (ED) visits or hospital
      admissions. OBJECTIVE: To determine the variation in ED visit rates for asthma in
      Ontario, and the relation between ED visit rates and hospitalization rates.
      DESIGN, SETTING, AND PATIENTS: We studied patients with an ED disposition
      diagnosis of asthma in a stratified sample of 16 hospitals (pediatric facilities,
      13; adult facilities, 14) over a 1-year period. Pediatric patients were defined
      as those patients who were </= 19 years of age. MEASUREMENTS: Direct age
      standardized and sex-standardized ED visit and hospitalization rates, and the
      percentages of patients presenting to EDs and subsequently admitted to the
      hospital were calculated for each site. High/low ratios (ie, extremal quotients
      [EQ]), weighted coefficients of variation (CVs), and the systematic component of
      variation (SCV) were used to summarize the variation among hospitals. RESULTS:
      The total number of ED visits for asthma at participating sites was 12,518 (7,825
      children and 4,693 adults). A total of 847 children (10.8%) and 322 adults (6.9%)
      were admitted to the hospital. Age-standardized and sex-standardized ED visit
      rates ranged from 8.7 to 25.2 per 1,000 population for children (EQ, 2.9; CV,
      30.9%; SCV, 173; p < 0.001) and 1.7 to 10.1 per 1,000 population for adults (EQ,
      5.9; CV, 52.9; SCV, 445; p < 0.001). The proportion of pediatric and adult ED
      visits resulting in admission to the hospital varied significantly by site (p <
      0.001) and was inversely related to ED visit rates in children (p < 0.001) but
      not in adults. ED visit rates were related to hospitalization rates in children
      (p = 0.042) and adults (p < 0.0001), but only accounted for 4% and 27%,
      respectively, of the variation in hospitalization rates. CONCLUSION:
      Hospitalization rates for asthma in Ontario are primarily influenced by the
      variation in the percentage of ED visitors admitted to the hospital rather than
      the ED visit rate.

PMID- 16608939
TI  - Using an asthma control questionnaire and administrative data to predict health
      care utilization.
AB  - OBJECTIVE: To examine the merits of the Asthma Therapy Assessment Questionnaire
      (ATAQ) control index together with prior asthma health-care utilization from
      administrative data in predicting future acute asthma health-care utilization.
      DESIGN: Prospective cohort study. POPULATION: A total of 4,788 adult asthma
      patients aged 17 to 93 years who completed a baseline evaluation and had at least
      6 months of follow-up data. STATISTICAL METHODS: Classification and regression
      tree methodology to predict future risk of acute health-care utilization events.
      RESULTS: These results show that the ATAQ control index and administrative data
      are jointly useful for predicting future health-care utilization. The utility of
      the ATAQ control index in the presence of information about prior health-care
      utilization is to further stratify risk among the subset of younger individuals
      who did not have any prior acute health-care utilization. While administrative
      health-care utilization data served as the strongest predictor of future health
      care utilization, the ATAQ control index helped to identify 1% of individuals
      without recent acute care that had approximately a sixfold elevated risk (95%
      confidence interval, 4.2 to 8.4) of future acute health-care utilization. This is
      an important result since only a small fraction of individuals with acute events
      in a given year will have had acute events in the previous year. CONCLUSION:
      These findings should assist the practicing clinician and organizations
      interested in population-based asthma disease management.

PMID- 16608940
TI  - Brief questionnaires for patient-reported outcomes in asthma: validation and
      usefulness in a primary care setting.
AB  - STUDY OBJECTIVES AND DESIGN: Health-related quality of life (QoL) instruments are
      generally used for studies of asthma in specialized settings. For primary care
      use, there is a need for brief and simple questionnaires for structured patient
      reported outcomes. We validated the Mini-Asthma Quality of Life Questionnaire
      (Mini-AQLQ), using the Asthma Quality of Life Questionnaire with standardized
      activities (AQLQ[S]) as the "gold standard." The Asthma Control Questionnaire
      (ACQ) was validated against the symptoms domain of the AQLQ(S). Patients were
      characterized by the Short Form-36 Health Survey (SF-36). SUBJECTS: One hundred
      eight patients (68 women) with asthma diagnosed by their physicians from 24
      primary care centers completed two visits (2 to 3 months apart). Their mean SF-36
      scores were lower than the national norm for all domains. RESULTS: The Mini-AQLQ
      and ACQ correlated well with the AQLQ(S). Reliability, determined in 57 patients
      with stable AQLQ(S) scores, was good. Both brief questionnaires detected
      improvement or deterioration of patients at the group level. Global ratings of
      disease severity by patients or clinicians correlated poorly with disease
      specific QoL scores. CONCLUSIONS: The Mini-AQLQ and ACQ instruments are
      sufficiently simple and robust to be suitable for research and quality of care
      monitoring in primary care at the group level. They may, after further
      validation, even be useful in the management of individual patients.

PMID- 16608941
TI  - Risk factors associated with snoring in women with special emphasis on body mass
      index: a population-based study.
AB  - STUDY OBJECTIVES: Habitual snoring may be regarded as an indicator of sleep
      disordered breathing, and the health consequences of sleep-disordered breathing
      are well-known. The aim of this study was to analyze the risk factors associated
      with habitual snoring in a large sample of women, with special emphasis on the
      determinants of snoring in women with different body mass index (BMI) levels.
      DESIGN AND SETTING: A cross-sectional, epidemiologic, population-based study was
      performed by using a postal questionnaire that was sent to a randomly selected
      sample of 6,817 women >/= 20 years of age in Uppsala, Sweden. RESULTS: The total
      prevalence of self-reported habitual snoring was 7.6%. There was a clear age
      dependence, with the highest prevalence of habitual snoring (14%) occurring
      between the ages of 50 and 59 years. Self-reported habitual snoring was related
      to BMI, neck circumference, and smoking >/= 10 cigarettes a day, after adjusting
      for possible confounders. When analyzing the influence of different risk factors
      in separate BMI groups, the results varied among the groups. The influence of
      alcohol dependence on snoring frequency was only significant in women with a BMI
      of < 20 kg/m(2), while physical inactivity was only associated with habitual
      snoring in women with a BMI of >/= 30 kg/m(2). CONCLUSIONS: The prevalence of
      self-reported habitual snoring in women was strongly dependent on age and BMI.
      The importance of other risk factors differed depending on BMI, with alcohol
      dependence being associated with self-reported snoring in lean women, whereas
      physical inactivity was a risk factor for self-reported snoring in women with a
      high BMI.

PMID- 16608942
TI  - Atopy as a risk factor for habitual snoring at age 1 year.
AB  - STUDY OBJECTIVES: To determine the prevalence of habitual snoring (HS) in 1-year
      old children, and to assess the relationship between HS and atopic status in
      these children. DESIGN: Cross-sectional evaluation of a birth cohort selected
      from the population. SETTING: Ohio and Kentucky River Valley communities.
      PARTICIPANTS: Children participating in the Cincinnati Childhood Allergy and Air
      Pollution Study (CCAAPS) were recruited for this study. MEASUREMENTS AND RESULTS:
      At age 1 year, the children were evaluated for atopic status and exposure to
      environmental tobacco smoke (ETS). Parents were asked to complete a questionnaire
      pertaining to their snoring frequency and that of their child. Children with HS
      (snoring three or more times per week) were compared to those who either did not
      snore or snored less than three times per week. Data were available on 681 of the
      700 children participating in CCAAPS study. Of these 681 children (377 boys and
      304 girls), 542 were white (80%), 118 were African American (17%), and 21 were
      biracial or Asian (3%). The mean age (+/- SD) of our cohort at the time of
      assessment for snoring was 13.7 +/- 2.6 months. Of the 681 children, 105 snored
      habitually (15%). There was a significant association between HS and the
      following: (1) positive atopic status (p = 0.005); (2) African-American race (p <
      0.01); and (3) a history of snoring in the father (p < 0.01) or in the mother (p
      < 0.01). There was, however, no association between HS and ETS. CONCLUSIONS: We
      found a 15% prevalence of HS in 1-year-old children born to atopic parents and a
      significant association with positive atopic status.

PMID- 16608943
TI  - Plasma adhesion molecules in children with sleep-disordered breathing.
AB  - STUDY OBJECTIVES: To determine whether childhood sleep-disordered breathing (SDB)
      is associated with elevated levels of plasma adhesion molecules. DESIGN:
      Prospective, observational study. SETTING: Sleep Medicine Center of Kosair
      Children's Hospital. PARTICIPANTS: Thirty-nine children with SDB (apnea-hypopnea
      index [AHI] > 5/h), 47 children with mild SDB (AHI 1 to 5/h), and 42 healthy
      control subjects (AHI < 1/h). MEASUREMENTS AND RESULTS: One hundred twenty-eight
      children underwent a standard polysomnographic assessment with a blood draw the
      following morning. Plasma levels of CRP and the adhesion molecules intercellular
      adhesion molecule (ICAM)-1 and P-selectin were measured. No differences were
      observed in ICAM-1 levels among the groups; however, obese children had higher
      ICAM-1 levels than nonobese children (425.0 +/- 123.0 ng/mL vs 375.6 +/- 107.1
      ng/mL, p = 0.04) [mean +/- SD]. P-selectin levels were significantly higher in
      the SDB group (84.0 +/- 52.2 ng/mL) and the mild SDB group (89.3 +/- 49.9 ng/mL)
      when compared to control subjects (49.5 +/- 22.3 ng/mL; p < 0.001 for both
      groups). Furthermore, P-selectin correlated with AHI (r = 0.32, p < 0.001),
      respiratory arousal index (r = 0.27, p = 0.002), and nadir of oxygen saturation
      as measured by pulse oximetry (r = - 0.19, p = 0.038). Plasma CRP levels were
      found to correlate with P-selectin even after controlling for BMI (r = 0.20, p =
      0.05). No correlations were found between CRP and ICAM-1. CONCLUSIONS: Children
      with SDB have plasma elevations of P-selectin, a marker of platelet activation,
      lending support to the premise that inflammatory processes are elicited by SDB in
      children, and may contribute to accelerated risk for cardiovascular morbidity. In
      contrast, elevations in ICAM-1 are primarily associated with obesity rather than
      SDB.

PMID- 16608944
TI  - Long-term mortality outcome associated with prolonged admission to the ICU.
AB  - STUDY OBJECTIVES: Patients requiring prolonged admission to the ICU consume
      significant health-care resources and have a high rate of in-hospital death. The
      long-term mortality outcome of these patients has not been well defined in a
      nonselected cohort. The objective of this study was to describe the occurrence
      and factors predictive of prolonged ICU stay at admission, and to define the long
      term (>/= 1 year) mortality outcome. DESIGN: Population-based cohort. SETTING:
      All adult multisystem and cardiovascular surgical ICUs in the Calgary Health
      Region (CHR) from July 1, 1999, to March 31, 2002. PATIENTS: Adult (>/= 18 years
      old) residents of the CHR admitted to regional ICUs. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: During the study, 4,845 patients had a median length of
      stay of 2 days (interquartile range, 1 to 4 days); 2,115 patients (44%) were
      admitted for < 2 days, 1,496 patients (31%) were admitted for 2 to 3 days; 1,018
      patients (21%) were admitted from 4 to 13 days; and 216 patients (4%) had a
      prolonged (>/= 14 day) admission to the ICU. A higher severity of illness, the
      presence of shock, and bloodstream infection were independently associated with a
      prolonged ICU admission, and cardiovascular surgery was associated with a lower
      risk. Patients with prolonged ICU admissions were nearly twice as likely to die
      as patients with shorter ICU admissions: 53 of 216 patients (25%) vs 584 of 4,629
      patients (13%) [p = 0.0001]. Among the 3,924 survivors to hospital discharge, the
      rates of mortality during the year following ICU admission were as follows: 59
      deaths in 1,758 patients (3%) admitted < 2 days, 74 deaths in 1,267 patients (6%)
      with 2- to 3-day admissions, 78 deaths in 766 patients (10%) with 4- to 13-day
      admissions, and 10 deaths in 133 patients (8%) with admissions >/= 14 days.
      CONCLUSIONS: One in 25 critically ill patients will have prolonged ICU admission
      and higher ICU-related mortality. However, survivors of prolonged ICU admission
      have good long-term mortality outcome after acute illness.

PMID- 16608945
TI  - Effects of early enteral feeding on the outcome of critically ill mechanically
      ventilated medical patients.
AB  - STUDY OBJECTIVES: To determine the impact of early enteral feeding on the outcome
      of critically ill medical patients. DESIGN: Retrospective analysis of a
      prospectively collected large multi-institutional ICU database. PATIENTS: A total
      of 4,049 patients requiring mechanical ventilation for > 2 days. MEASUREMENTS AND
      RESULTS: Patients were classified according to whether or not they received
      enteral feeding within 48 h of mechanical ventilation onset. The 2,537 patients
      (63%) who did receive enteral feeding were labeled as the "early feeding group,"
      and the remaining 1,512 patients (37%) were labeled as the "late feeding group."
      The overall ICU and hospital mortality were lower in the early feeding group
      (18.1% vs 21.4%, p = 0.01; and 28.7% vs 33.5%, p = 0.001, respectively). The
      lower mortality rates in the early feeding group were most evident in the sickest
      group as defined by quartiles of severity of illness scores. Three separate
      models were done using each of the different scores (acute physiology and chronic
      health evaluation II, simplified acute physiology score II, and mortality
      prediction model at time 0). In all models, early enteral feeding was associated
      with an approximately 20% decrease in ICU mortality and a 25% decrease in
      hospital mortality. We also analyzed the data after controlling for confounding
      by matching for propensity score. In this analysis, early feeding was again
      associated with decreased ICU and hospital mortality. In all adjusted analysis,
      early feeding was found to be independently associated with an increased risk of
      ventilator-associated pneumonia (VAP) developing. CONCLUSION: Early feeding
      significantly reduces ICU and hospital mortality based mainly on improvements in
      the sickest patients, despite being associated with an increased risk of VAP
      developing. Routine administration of such therapy in medical patients receiving
      mechanical ventilation is suggested, especially in patients at high risk of
      death.

PMID- 16608946
TI  - Severe sepsis in community-acquired pneumonia: when does it happen, and do
      systemic inflammatory response syndrome criteria help predict course?
AB  - STUDY OBJECTIVES: Most natural history studies of severe sepsis are limited to
      ICU populations. We describe the onset and timing of severe sepsis during the
      hospital course for patients hospitalized with community-acquired pneumonia
      (CAP). We also determine the ability of the systemic inflammatory response
      syndrome (SIRS) and other proposed risk stratification scores measured at
      emergency department (ED) presentation to predict progression to severe sepsis,
      septic shock, or death. DESIGN: Retrospective analysis of a prospective
      observational outcome study from the Pneumonia Patient Outcomes Research Team
      (PORT). SETTING: Four academic medical centers in the United States and Canada
      between October 1991 and March 1994. PARTICIPANTS: The 1,339 patients
      hospitalized for CAP in the PORT study cohort, and a random subset of 686
      patients for whom we had information for SIRS criteria. INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: All subjects had infection (CAP). Severe sepsis was
      defined as new-onset acute organ dysfunction in this cohort, using consensus
      criteria. Severe sepsis developed in one half of the patients (n = 639, 48%),
      nonpulmonary organ dysfunction developed in 520 patients (39%), and septic shock
      developed in 61 subjects (4.5%). Severe sepsis and septic shock were present at
      ED presentation in 457 patients (71% of severe sepsis cases) and 27 patients (44%
      of septic shock cases), respectively. While SIRS was common at presentation (82%
      of the subset of 686 had two SIRS criteria), it was not associated with increased
      odds for progression to severe sepsis (odds ratios [ORs], 0.65 and 0.89 for two
      or more SIRS criteria and three or more SIRS criteria, respectively), septic
      shock (ORs, 0.80 and 0.55), or death (ORs, 0.65 and 0.39), with poor
      discrimination (all receiver operating characteristic [ROC] areas under the curve
      < 0.5). The pneumonia severity index was associated with severe sepsis (p <
      0.001) with moderate discrimination (ROC, 0.63). CONCLUSIONS: Severe sepsis is
      common in hospitalized CAP patients, occurring early in the hospital course. SIRS
      criteria do not appear to be useful predictors for progression to severe sepsis
      in CAP.

PMID- 16608947
TI  - "Tobacco Free With FDNY": the New York City Fire Department World Trade Center
      Tobacco Cessation Study.
AB  - CONTEXT: After the World Trade Center (WTC) collapse, 15% (1,767) of rescue
      workers from the Fire Department of the City of New York (FDNY) considered
      themselves to be current cigarette smokers. Post-WTC collapse, 98% reported acute
      respiratory symptoms, and 81% reported health concerns. Nonetheless, 29% of
      current smokers increased tobacco use, and 23% of ex-smokers resumed cigarette
      smoking. OBJECTIVE: To determine the effect of a comprehensive tobacco-cessation
      program using combination tobacco-dependency treatment medications adjusted to
      the individual's daily tobacco use. DESIGN: FDNY cigarette smokers enrolled in
      "Tobacco Free With FDNY," a no-cost quit-smoking program providing counseling,
      support, and medications. At the end of the 3-month treatment phase and at the 6
      month and 12-month follow-up visits, abstinence rates were confirmed by expired
      carbon monoxide levels or by the verification of a household member. SETTING:
      FDNY Bureau of Health Services between August 1, 2002 and October 30, 2002.
      PARTICIPANTS: A total of 220 current cigarette smokers from the FDNY. RESULTS: At
      study enrollment, the mean (+/- SD) tobacco use was 20 +/- 7 cigarettes per day,
      and the mean tobacco dependency, as assessed by a modified Fagerstrom test score,
      was 6.7 +/- 2.5 (maximum score, 10). Based on tobacco use, 20% of enrollees used
      three types of nicotine medications, 64% used two types, 14% used one type, and
      3% used no medications. Additionally, 14% of enrollees used bupropion sustained
      release. The confirmed continuous abstinence rates were 47%, 36%, and 37%,
      respectively, after 3 months of treatment and at the 6-month and 12-month follow
      up. Abstinence rates did not correlate with the history of tobacco use but
      correlated inversely with tobacco dependency. Adverse events and maximal nicotine
      medication use were unrelated, and no one experienced a serious adverse event.
      CONCLUSION: Tobacco dependency treatment using combination nicotine medications
      is effective and safe. Future studies should consider the following: (1) both
      history of tobacco use and withdrawal symptoms to determine the number and dose
      of nicotine medications; and (2) continuing combination treatment for > 3 months.

PMID- 16608948
TI  - Real-time electromagnetic navigation bronchoscopy to peripheral lung lesions
      using overlaid CT images: the first human study.
AB  - STUDY OBJECTIVES: To characterize the feasibility, accuracy, and safety of the
      superDimension/Bronchus system (SDBS) [superDimension, Ltd; Hertzliya, Israel] in
      navigating to previously unreachable peripheral lung lesions and obtaining biopsy
      specimens. DESIGN: Open-label, prospective, controlled clinical study. SETTING:
      Pulmonary institute of a university-affiliated municipal hospital. PATIENTS:
      Thirteen adult candidates for nonemergency bronchoscopy who gave informed consent
      to participate. INTERVENTIONS: The patients underwent flexible bronchoscopy using
      the SDBS, which is based on real-time CT-guided electromagnetic navigation and is
      capable of reaching peripheral lung masses beyond the reach of the bronchoscope.
      A position sensor was used to navigate to and sample the various target lesions
      for biopsy. MEASUREMENTS AND RESULTS: Three-dimensional chest CT was followed by
      SDBS methodology for marking anatomic landmarks and the target lesion on a
      virtual bronchoscopy screen and for sampling the lesion. The SDBS assisted in
      obtaining positive biopsy diagnoses in 9 of 13 cases (69%), with an average
      navigation accuracy of 5.7 mm. There were no SDBS-related adverse events.
      CONCLUSIONS: The SDBS is safe and effective in navigating to peripheral lung
      lesions located beyond the optic limits of a standard flexible bronchoscope.

PMID- 16608949
TI  - Optical spectroscopy for the classification of malignant lesions of the bronchial
      tree.
AB  - Optical spectroscopy may be used for in vivo, noninvasive distinction of
      malignant from normal tissue. The aim of our study was to analyze the accuracy of
      various optical spectroscopic techniques for the classification of cancerous
      lesions of the bronchial tree. We developed a fiberoptic instrument allowing the
      measurement of autofluorescence spectroscopy (AFS), diffuse reflectance
      spectroscopy (DRS), and differential path length spectroscopy (DPS) during
      bronchoscopy. Spectroscopic measurements were obtained from 191 different
      endobronchial lesions (63 malignant and 128 nonmalignant) in 107 patients. AFS,
      DRS, and DPS sensitivity/specificity for the distinction between malignant and
      nonmalignant bronchial lesions were 73%/82%, 86%/81%, and 81%/88%, respectively.
      All three optical spectroscopic modalities facilitate an increase of the positive
      predictive value of autofluorescence bronchoscopy for the detection of
      endobronchial tumors. Even better results were obtained when the three
      spectroscopic techniques were combined.

PMID- 16608950
TI  - Pretransplantation bone disease in patients with primary pulmonary hypertension.
AB  - INTRODUCTION: Osteoporosis is a common condition in patients with end-stage lung
      disease, but little attention has been given to bone disease in patients with
      primary pulmonary hypertension (PPH). The purposes of this study were as follows:
      (1) to determine the prevalence of osteoporosis in patients with severe PPH
      before lung transplantation, (2) to investigate whether generally accepted risk
      factors for osteoporosis would play a role in this special group of patients, and
      (3) to determine whether there is an association between functional parameters
      and pretransplantion bone mass. DESIGN: A retrospective analysis of 18
      consecutive patients with PPH accepted for lung transplantation at the University
      Hospital of Zurich. MEASUREMENTS AND RESULTS: Decreased bone mineral density
      (BMD) [T score <- 1.0] was found in 11 of 18 patients (61%) at the femoral neck
      (FN) and 13 of 18 patients (72%) at the lumbar spine (LS). We did not find a
      significant difference of BMD in a gender- or age-specific manner. Body mass
      index (BMI) correlated significantly with BMD and T score at the FN and WT.
      Pulmonary vascular resistance (PVR) was notably linked with BMD at the FN. We
      found a positive association between walking distance in the 12-min walking test
      and BMD at the FN and WT. CONCLUSIONS: Low bone density is a very frequent
      condition in patients with severe PPH. In contrast to the general population, in
      our study group neither age nor female gender were significantly associated with
      lower bone mass. Body weight and BMI were highly coupled with BMD. Among the
      functional parameters, walking distance and PVR were correlated to BMD at the FN.
      Considering that patients with PPH may have an improved life expectancy in the
      future, the early diagnosis, prevention, and treatment of osteoporosis should
      receive high priority.

PMID- 16608951
TI  - Efficacy of bosentan in a small cohort of adult patients with pulmonary arterial
      hypertension related to congenital heart disease.
AB  - OBJECTIVES: This study was designed to assess the tolerability and efficacy of
      the oral endothelin receptor antagonist bosentan in adult patients with pulmonary
      arterial hypertension (PAH) related to congenital heart disease (CHD).
      BACKGROUND: Severe PAH in the setting of CHD is a debilitating syndrome for which
      there are limited treatment options. This is the first long-term study experience
      in adults reporting on the tolerability and efficacy of therapy with bosentan for
      this patient population. METHODS: A 12-month single-center experience with 19
      women and 5 men with PAH associated with CHD (79% in New York Heart Association
      [NYHA] class III) was analyzed. Hemodynamic responses, exercise capacity, and
      Borg dyspnea index were assessed prior to the administration of bosentan, and
      again at 3, 6, and 12 months after the study began. Clinical assessments were
      performed monthly for up to 12 months. The change from baseline was tested using
      the Wilcoxon pairs test. RESULTS: There was significant improvement in
      hemodynamics from baseline to 12 months (mean [+/- SD] systolic pulmonary
      arterial pressure, 99 +/- 30 to 87 +/- 28 mm Hg [p </= 0.001]; mean pulmonary
      arterial pressure, 60 +/- 18 to 52 +/- 17 mm Hg [p </= 0.001]; mean right atrial
      pressure, 12 +/- 6 to 8 +/- 5 mm Hg [p </= 0.001]; mean pulmonary vascular
      resistance, 663 +/- 386 to 504 +/- 307 dyne . s . cm(-5) [p < 0.01]; pulmonary
      capillary wedge pressure, 15 +/- 5 to 11 +/- 3 mm Hg [p < 0.001]). NYHA
      functional class also improved from baseline to 12 months (NYHA class I/II range,
      17 to 71%; p < 0.001). There was a marginally significant trend toward
      improvement in the mean 6-min walk test distance at 12 months (299 +/- 85 to 330
      +/- 95 m; p = 0.05). Three patients needed to discontinue bosentan therapy
      because of elevated liver function test results. There were no deaths or
      hospitalizations, and no significant change in arterial oxygen saturation had
      occurred at 12 months. CONCLUSIONS: Bosentan therapy improved hemodynamics and
      NYHA class in patients with PAH that was associated with CHD. These effects were
      seen after 3 to 6 months. Bosentan therapy may provide an effective alternative
      to current therapies in this patient population.

PMID- 16608952
TI  - Pathologic correlates of bronchiolitis obliterans syndrome in pulmonary
      retransplant recipients.
AB  - RATIONALE: The main hindrance to long-term success of lung transplantation is
      bronchiolitis obliterans syndrome (BOS), generally thought to be a manifestation
      of chronic allograft rejection. BOS is associated histologically with epithelial
      injury, bronchocentric mononuclear inflammation, and fibrosis of small airways
      known as bronchiolitis obliterans (BO). Few studies have directly compared
      clinical, radiographic, and histologic findings of BOS and BO, particularly in
      the era of improved immunosuppression and infection prophylaxis. Patients
      undergoing pulmonary retransplantation for BOS provide a unique opportunity to
      investigate these relationships. METHODS: All patients who underwent pulmonary
      retransplantation for BOS from 1992 to 2004 at Duke University Medical Center
      were reviewed. Pathology findings in explanted lung allografts were compared with
      clinical, radiographic, and transbronchial biopsy data. RESULTS: Over the 12-year
      study period, 12 patients underwent pulmonary retransplantation for BOS. The
      median time to BOS was 517 days (intraquartile range, 396 to 819.8 days). BOS
      scores prior to retransplantation were 2 in 2 patients and 3 in 10 patients. We
      developed a semiquantitative scoring system for epithelial, inflammatory, and
      fibrotic changes in affected airways to permit better comparison between BO and
      BOS. Somewhat surprisingly, only 50% (6 of 12 patients) had severe fibrotic
      changes, although all had some degree of epithelial injury, fibrosis, or
      inflammation centered around the bronchi and bronchioles. Furthermore, pathology
      findings other than BO were present in most explanted allografts and included
      cholesterol clefts (n = 4), focal invasive aspergillosis (n = 1), interstitial
      fibrosis (n = 2), and chronic vascular rejection (n = 1). CONCLUSIONS: In this
      series of patients with advanced BOS undergoing retransplantation, at least some
      degree of BO was present in all explanted allografts. However, the degree of
      epithelial changes, fibrosis, and inflammation present among affected bronchi
      varied considerably. Furthermore, a wide range of pathologic processes of
      potential clinical significance were evident in half of the patients. We conclude
      that significant histologic heterogeneity exists among patients undergoing
      retransplantation for BOS, potentially contributing to the variability of patient
      responses to treatment.

PMID- 16608953
TI  - Inhaled nitric oxide does not prevent pulmonary edema after lung transplantation
      measured by lung water content: a randomized clinical study.
AB  - STUDY OBJECTIVE: In order to assess the effects of inhaled nitric oxide (iNO) in
      preventing early-onset lung edema from occurring after lung transplantation, we
      measured extravascular lung water (EVLW) in a group of lung transplant recipients
      who were at high risk for developing ischemia-reperfusion-induced lung injury.
      DESIGN: Prospective, randomized study. SETTINGS: Surgical ICU in a teaching
      hospital. PATIENTS: Thirty double-lung transplant recipients. INTERVENTIONS:
      Patients were randomized to receive or not receive 20 ppm iNO at the time of
      reperfusion (ie, before any occurrence of lung edema). In the NO group, iNO was
      then administered for a 12-h period. A double-dilution technique was used for the
      serial assessment of EVLW, intrathoracic blood volume, and cardiac index.
      Standard hemodynamic and pulmonary parameters were also recorded during the first
      3 postoperative days. MEASUREMENTS AND RESULTS: Patients who received iNO did not
      have a different lung water content compared to control subjects (p = 0.61 [by
      analysis of variance (ANOVA)]). Blood oxygenation (ie, Pao(2)/fraction of
      inspired oxygen [Fio(2)] ratio) did not differ between the two groups (p = 0.61
      [by ANOVA]). In both groups, EVLW and Pao(2)/Fio(2) ratio dropped significantly
      over time, regardless of the use of iNO (p < 0.01 [by ANOVA]). CONCLUSIONS: In
      the population studied, prophylactic iNO that was administered at 20 ppm had no
      effect on pulmonary edema formation and resolution following lung
      transplantation.

PMID- 16608954
TI  - A randomized trial of different docetaxel schedules in non-small cell lung cancer
      patients who failed previous platinum-based chemotherapy.
AB  - STUDY OBJECTIVE: Docetaxel has shown activity in the second-line treatment of non
      small cell lung cancer (NSCLC). Phase II studies have suggested that weekly
      therapy with docetaxel probably has a better toxicity profile than the
      conventional schedule of once every 3 weeks. Our aim was to evaluate and compare
      the efficacy of different docetaxel schedules in NSCLC patients who did not
      respond to previous platinum-based chemotherapy. SETTING: National teaching
      hospital in Taiwan. METHODS: Treatment consisted of the following: (1) docetaxel,
      35 mg/m(2) IV infusion (D(35)) on days 1, 8, and 15 every 4 weeks; (2) docetaxel,
      40 mg/m(2) IV (D(40)) on days 1 and 8 every 3 weeks; and (3) docetaxel, 75
      mg/m(2) IV (D(75)) on day 1 every 3 weeks. Patients were randomized at a ratio of
      2:2:1, with the D(75) arm as the control arm. From 2002 to 2004, 161 patients
      were enrolled into the study. RESULTS: The number of patients enrolled in each
      arm of the study was as follows: D(35) group, 64 patients; D(40) group, 64
      patients; D(75) group, 33 patients. The mean ages of patients were as follows:
      D(35) group, 65 years of age; D(40) group, 63 years of age; D(75) group, 64 years
      of age. The median number of cycles of chemotherapy received in each group was as
      follows: D(35) group, 4; D(40) group, 3; D(75) group, 4. The objective response
      rates were as follows: D(35) group, 17.2%; D(40) group, 10.9%; D(75) group, 6.1%
      (p = 0.615). The major toxicity was myelosuppression. Grades 3/4 leukopenia and
      neutropenia were significantly higher in the D(75) arm of the study (p < 0.001).
      Drug-induced pneumonitis occurred more frequently in patients on a weekly
      schedule than in those on a schedule of every 3-weeks (p = 0.05). The median
      survival times were as follows: D(35) group, 8.4 months; D(40) group, 7.2 months;
      and D(75) group, 9.5 months (p = 0.855). The 1-year survival rates were 32.8%,
      31.9%, and 28.7%, respectively. Lung cancer symptom scores showed no obvious
      differences among the different treatment arms, except for some minor items.
      CONCLUSIONS: Weekly docetaxel chemotherapy produces less myelosuppression, and
      better compliance and response rates than the conventional chemotherapy
      administered every 3 weeks. These effects were more evident in the D(35) group
      weekly schedule than in the D(40) weekly schedule. However, physicians should pay
      more attention to the possibility of a higher frequency of docetaxel-induced
      pneumonitis in patients receiving treatment on the weekly schedule of treatment.

PMID- 16608955
TI  - CT screening for lung cancer: the value of short-term CT follow-up.
AB  - BACKGROUND: Although CT screening for lung cancer results in a diagnosis of stage
      I > 80% of the time, benign noncalcified nodules are also found. We recognized
      that some nodules appeared to represent infectious bronchopneumonia or other
      inflammatory processes, as they resolved on follow-up CT, sometimes after
      antibiotic therapy. To determine the extent to which short-term CT radiographic
      follow-up might shorten the workup of nodules, we reviewed our experience with
      baseline and annual repeat CT screenings performed subsequent to the original
      Early Lung Cancer Action Project series. METHODS: The initial CT of 1,968
      consecutive baseline and 2,343 annual repeat screenings performed from 1999 to
      2002 was reviewed. We identified all those recommended for antibiotics on the
      initial CT who had a follow-up CT within 2 months and determined whether the
      nodule(s) resolved, decreased in size, remained unchanged, or grew. We then
      determined whether further follow-up resulted in a diagnosis of cancer. RESULTS:
      At baseline, among the 41 individuals who had follow-up CT within 2 months of the
      initial CT, 12 patients (29%) had complete or partial resolution; none of them
      subsequently received a diagnosis of lung cancer. On annual repeat screening,
      among the 39 individuals who had follow-up CT within 2 months of the initial CT,
      29 patients (74%) had complete or partial resolution; none of them subsequently
      received a diagnosis of lung cancer. Among the 29 patients with nodules at
      baseline that were unchanged or grew, a total of 15 cancers were subsequently
      diagnosed; among the 10 patients on annual repeat scanning, there were 2 cancers.
      CONCLUSIONS: In asymptomatic individuals undergoing CT screening for lung cancer,
      short-term follow-up CT within 2 months with or without antibiotics may
      circumvent the need for further evaluation in some individuals, particularly on
      annual repeat screening.

PMID- 16608956
TI  - Management of unsuccessful thrombolysis in acute massive pulmonary embolism.
AB  - BACKGROUND: The management of patients with acute massive pulmonary embolism (PE)
      who do not respond to fibrinolytic therapy remains unclear. We aimed to compare
      rescue surgical embolectomy and repeat thrombolysis in patients who did not
      respond to thrombolysis. METHODS: We conducted a prospective single-center
      registry of PE patients who underwent thrombolytic therapy. Lack of response to
      thrombolysis within the first 36 h was prospectively defined as both persistent
      clinical instability and residual echocardiographic right ventricular
      dysfunction. Patients underwent surgical embolectomy or repeat thrombolysis, at
      the discretion of the attending physician. The clinical end point was a combined
      end point including recurrent PE, bleeding complications, or PE-related death,
      which was defined as death from recurrent PE or cardiogenic shock. Long-term
      adverse outcomes included death, recurrent thromboembolic events, and congestive
      heart failure. RESULTS: From January 1995 to January 2005, 488 PE patients
      underwent thrombolysis, of whom 40 (8.2%) did not respond to thrombolysis.
      Fourteen patients were treated by rescue surgical embolectomy, and 26 were
      treated by repeat thrombolysis. There was no significant difference in baseline
      characteristics between the two groups. The in-hospital course was uneventful in
      11 of the surgically treated patients (79%) and in 8 patients (31%) treated by
      repeat thrombolysis (p = 0.004). There was a trend for higher mortality in the
      medical group than in the surgical group (10 vs 1 deaths, respectively; p =
      0.07). There were significantly more recurrent PEs (fatal and nonfatal) in the
      repeat-thrombolysis group (35% vs 0%, respectively; p = 0.015). While no
      significant difference was observed in number of major bleeding events, all
      bleeding events in the repeat-thrombolysis group were fatal. The rate of
      uneventful long-term evolution was the same in the two groups. CONCLUSION: Rescue
      surgical embolectomy led to a better in-hospital course when compared with repeat
      thrombolysis in patients with massive PE who have not responded to thrombolysis.
      The transfer of patients who have not responded to thrombolysis to tertiary
      cardiac surgery centers could be considered as an alternative option.

PMID- 16608957
TI  - The relation between gastroesophageal reflux and respiratory symptoms in a
      population-based study: the Nord-Trondelag health survey.
AB  - BACKGROUND: In spite of numerous investigations, the relation between respiratory
      symptoms and reflux symptoms in the general population remains unclear, since
      population-based studies are few. STUDY OBJECTIVES: To investigate the relation
      between respiratory symptoms and reflux symptoms in the population. SUBJECT AND
      METHODS: In a cohort of 65,363 individuals representing 71.2% of the adult
      population in the Norwegian county of Nord-Trondelag, 58,596 individuals (89.6%)
      responded to questions concerning reflux symptoms. The 3,153 persons (5.4%) with
      severe and recurrent reflux symptoms constituted the case group, and the 40,210
      persons (68.6%) without reflux symptoms served as the control group. Odds ratios
      (ORs) with 95% confidence intervals (CIs) represented relative risks. Potential
      confounding was tested in multivariable logistic regression analysis. RESULTS:
      Persons with asthma had reflux to a 60% greater extent than those without asthma
      after including adjustment for asthma medication (OR, 1.6; 95% CI, 1.4 to 1.9).
      There was a statistically significant dose-response association between
      breathlessness and reflux symptoms (p for trend < 0.0001), and the OR of severe
      breathlessness was 12.0 (95% CI, 9.5 to 15.2). Persons with heavy and wheezy
      breathing, daily cough, daily productive cough, or chronic cough showed a twofold
      to threefold statistically significant increase in risk of reflux symptoms.
      Adjustment for asthma or use of asthma medication did not substantially influence
      the risk estimates for any of the studied respiratory disorders. CONCLUSIONS:
      Reflux symptoms commonly coexist with asthma and other respiratory symptoms on a
      population-based level, seemingly irrespective of asthma medication.

PMID- 16608958
TI  - Applied medical informatics for the chest physician: information you can use!-
      Part 3.
AB  - In this third and last part in our series on applied medical informatics (AMI),
      we will examine the following: (1) a concise wrap-up of the practice steps
      necessary to achieve the benefits from AMI in your practice; (2) an introduction
      to the patient health-care record and why it is important to physicians; and (3)
      a look at some of the latest developments in AMI that are of interest to the
      chest physician.

PMID- 16608959
TI  - Intensive care and emergency medicine: progress over the past 25 years.
AB  - Over the last quarter of a century, intensive care medicine has developed into an
      established hospital specialty with its own unique identity and characteristics.
      Significant advances have occurred, mostly in a succession of small steps rather
      than any dramatic leap, with many being linked to advances in health care across
      other disciplines. In addition, many changes have resulted from the scientific
      identification of the detrimental effects of certain traditional practices once
      thought to be therapeutic. Here, in an attempt to learn from the past and offer
      guidance for future progress, we detail some of the key changes in various
      aspects of intensive care medicine including respiratory, cardiovascular,
      metabolic, and nutritional care, as well as sepsis, polytrauma, organization, and
      management.

PMID- 16608960
TI  - Structural changes in airway diseases: characteristics, mechanisms, consequences,
      and pharmacologic modulation.
AB  - In airway diseases such as asthma and COPD, specific structural changes may be
      observed, very likely secondary to an underlying inflammatory process. Although
      it is still controversial, airway remodeling may contribute to the development of
      these diseases and to their clinical expression and outcome. Airway remodeling
      has been described in asthma in various degrees of severity, and correlations
      have been found between such features as increase in subepithelial collagen or
      proteoglycan deposits and airway responsiveness. Although the clinical
      significance of airway remodeling remains a matter of debate, it has been
      suggested as a potential target for treatments aimed at reducing asthma severity,
      improving its control, and possibly preventing its development. To date, drugs
      used to treat airway diseases have a little influence on airway structural
      changes. More research should be done to identify key changes, valuable
      treatments, and proper interventional timing to counteract these changes. The
      potential of novel therapeutic agents to reverse or prevent airway remodeling is
      an exciting avenue and warrants further evaluation.

PMID- 16608962
TI  - The uniform requirements for manuscripts submitted to biomedical journals
      recommended by the International Committee of Medical Journal Editors.

PMID- 16608961
TI  - Long-term survivorship in lung cancer: a review.
AB  - While outcome research in lung cancer has focused mainly on short-term survival
      and quality of life (QoL), information on long-term (ie, > 5 years postdiagnosis)
      lung cancer survivorship remains limited. This review addresses the epidemiologic
      significance of long-term lung cancer (LTLC) survivors, summarizes the current
      knowledge on their health and QoL, and suggests areas for further research in
      LTLC survivorship. Based on a small body of literature, lung cancer survivors do
      not experience the same quantity and QoL as their age-matched peers or as
      survivors of other cancers. Survival among 5-year survivors of lung cancer
      relative to the general US population with the same demographic characteristics
      is approximately 60%, and lung cancer survivors score lowest in health utility
      among long-term survivors of other cancers. Approximately one-quarter of long
      term lung cancer (LTLC) survivors were significantly restricted in physical
      ability or reported significant depressive symptoms. There is a need to identify
      and intervene with subgroups of survivors who are at an elevated risk of
      premature death and diminished QoL. Lung cancer-specific survival alone does not
      reflect the overall illness burden in LTLC survivors. Patient care in lung cancer
      survivors should be continuous and comprehensive in considering multiple causes
      of health deterioration. Multidisciplinary research in epidemiologic, clinical,
      and basic science approaches is warranted to further our knowledge base for
      optimal long-term management and to develop the necessary intervention strategies
      among LTLC survivors.

PMID- 16608963
TI  - Stridor in a 47-year-old man with inflammatory bowel disease.

PMID- 16608964
TI  - A 68-year-old man with intractable dyspnea and wheezing 45 years after a
      pneumonectomy.

PMID- 16608965
TI  - Are the American College of Chest Physicians guidelines for the prevention and
      management of atrial fibrillation after cardiac surgery already obsolete?

PMID- 16608966
TI  - Importance of appropriately adjusting diffusing capacity of the lung for carbon
      monoxide and diffusing capacity of the lung for carbon monoxide/alveolar volume
      ratio for lung volume.

PMID- 16608967
TI  - Cardiac sarcoidosis.

PMID- 16608968
TI  - Use of racemic epinephrine in bronchiolitis: what is the emergency physician's
      perspective?

PMID- 16608969
TI  - Einthoven's machine is alive and well today, although his contemporaries were not
      interested in it at all.

PMID- 16608970
TI  - Housing and health counseling: design and environmental results.

PMID- 16608971
TI  - Diagnostic and therapeutical management of malignant pleural effusion.

PMID- 16608972
TI  - Malignant pleural mesothelioma.

PMID- 16608973
TI  - Non-small cell lung cancer: early stages.

PMID- 16608974
TI  - Surgical procedures in mediastinal lung cancer staging.

PMID- 16608975
TI  - Locally advanced non-small cell lung cancer: different strategies for different
      diseases.

PMID- 16608976
TI  - Locally advanced non-small cell lung cancer: role of induction chemotherapy in
      resectable N2 disease.
AB  - Patients with resectable stage IIIA-N2 non-small cell lung cancer should receive
      induction chemotherapy before surgery. The aim is to early control systemic
      disease, eventually cure the mediastinal tumor spread and improve patients'
      survival. A recent metanalysis of randomized trials with second-generation
      platinum-based combinations has reinforced the evidence concerning the benefit of
      induction chemotherapy followed by surgery versus surgery alone in resectable
      disease. Moreover a large number of phase II trials have explored the activity
      and feasibility of platinum-based combinations with third-generation drugs in the
      same setting. Still opened questions to address with current clinical research
      are the eventual role of radiotherapy as induction treatment, the impact of
      definite chemoradiation versus induction treatment followed by surgical resection
      on local control and survival and finally the non-easy choice between neo
      adjuvant and adjuvant chemotherapy.

PMID- 16608977
TI  - Multimodality treatment in locally advanced non-small cell lung cancer.

PMID- 16608978
TI  - New radiation techniques for treatment of locally advanced non-small cell lung
      cancer (NSCLC).
AB  - Local control is a main step to cure NSCLC because at least 30-40% of patients
      die for local or regional progression of their disease. Surgery is still the more
      efficient approach to increase survival but radiation therapy is the only
      treatment that can cure patients with T1-T2 lesions if they are not suitable for
      surgery or refuse it. However, doses higher than 60-66 Gy must be given to
      improve tumor control but doses to the organs at risk (OAR) are the main limit to
      deliver more than 70 Gy to the planning treatment volume (PTV). The optimal
      solution would be to 'paint' the dose to the PTV avoiding as possible OARs, but
      this ballistic precision was not possible till some years ago because of both
      technology and respiratory movement control. In last ten years many new
      techniques have been made available for treating NSCLC with radiation more
      accurately. Some techniques like Intensity Modulated Radiotherapy (IMRT), Image
      Guided Radiotherapy (IGRT), Stereotactic Radiotherapy can be carried out also
      with a traditional linear accelerator (LINAC) updated with the new software and
      hardware, using or not radiopaque markers inside the tumor. On the other hand, a
      new generation of machines like Cyberknife or Tomotherapy have been especially
      projected to optimize stereotactic technique and IMRT, respectively, and
      respiratory gating systems are now disposable from several manufactures.

PMID- 16608979
TI  - Treatment of advanced non-small cell lung cancer.
AB  - In the last decade the treatment of advanced-metastatic non-small cell lung
      cancer has substantially improved. If in the early 90s there was still concern
      about the real efficacy of chemotherapy over best suppotive care alone in the
      advanced setting, constant developments in clinical research have demonstrated
      the survival advantage of active anti-cancer drugs not only in the first-line
      setting, but, lately, even in patients with recurrent disease after failure of
      two previous chemotherapy lines. With the premises of high throughput
      technologies, translational research is aiming to characterize patients and
      tumors on a molecular basis. With pharmacogenomics it would then be possible to
      accurately predict patient outcome and tailor the treatment strategy according to
      the geno-phenotype of single patients.

PMID- 16608980
TI  - Anti-cancer therapy with EGFR inhibitors: factors of prognostic and predictive
      significance.

PMID- 16608981
TI  - Small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
      in non-small cell lung cancer.
AB  - Despite recent developments in the diagnosis and conventional treatment of non
      small cell lung cancer (NSCLC), the prognosis remains unsatisfactory, with 5-year
      survival rates of approximately 15% for all stages. To date, chemotherapy
      represents the standard treatment for advanced-non small lung cancer, but
      efficacy of currently available cytotoxic drugs is modest. Median survival does
      not exceed 8-10 months. New treatment strategies are needed and considerable hope
      has been placed in therapies that specifically target the molecular mechanisms of
      tumour growth. One molecular target of particular relevance to lung cancer
      pathogenesis is the epidermal growth factor receptor (EGFR), a cell membrane
      receptor tyrosine kinase. Several inhibitors of EGFR fuctinonal activation have
      been developed. Amon these, erlotinib (Tarceva) and gefitinib (Iressa) are two
      orally bioavailable, small molecule EGFR inhibitors of the tyrosine kinase
      enzymatic activity which prevent EGFR autophosphorylation and activation. In
      monotherapy, gefitinib and erlotinib have determinated a 10-20% response rate and
      a 30-50% symptom improvement in previously treated, chemotherapy refractory,
      advanced NSCLC patients. Furthermore, a randomized, placebo controlled,
      multicenter phase III study has shown a two months improvement in median survival
      with erlotinib in the second or third line treatment of metastatic NSCLC
      patients. We will summarize the clinical evidence on the anticancer activity of
      small molecule EGFR inhibitors.

PMID- 16608982
TI  - Anti-EGFR monoclonal antibodies in the treatment of non-small cell lung cancer.

PMID- 16608983
TI  - Small cell lung cancer.
AB  - Small cell lung cancer accounts for 13-15% of all lung cancer worldwide. There
      has been a decrease in the number of cases, with no clear explanation, except
      probably to changing in smoking habits in the last two decades. In the early
      eighties, it became clear that SCLC was an extremely sensitive tumor as to
      radiation as to chemotheraputic agents. With cisplatinum etoposide combinations
      or cyclophosphamide, anthracycline and vincristine/etyoposide regimens responses
      were observed in 50-70%, with 20-30% complete remissions in extensive disease.
      For limited stage patients chemotherapy associated with thoracic radiation was
      able to produce a cure rate of 10-20%. The addition of prophylactic brain
      irradiation to limited stage cases has reduced mortality by a factor of nearly
      5%. But despite these early good results no breakthrough came later on, and in
      the last decade or so, we are still facing this plateau. New agents have recently
      been included in the therapeutic armamentarium, such as gemcitabine, irinotecan,
      paclitaxel. This fact has allowed many patients to receive a relatively active
      second line therapy, but the overall survival remains unchanged. Targeted
      therapies are undergoing some evaluations, but the data are too premature and so
      far quite discouraging. At the present time there is a urgent need to improve
      clinical research in this somehow forgotten disease.

PMID- 16608984
TI  - Combination of biological therapies in non-small cell lung cancer.

PMID- 16608986
TI  - Chemotherapy of advanced non-small cell lung cancer in elderly patients.
AB  - Non-small cell lung cancer (NSCLC) may be considered typical of advanced age.
      More than 50% of NSCLC patients are diagnosed over the age of 65 and
      approximately one-third of all patients are over the age of 70. Elderly patients
      tolerate chemotherapy poorly compared to their younger counterpart because of the
      progressive reduction of organ function and comorbidities related to age. For
      this reason, these patients are often not considered eligible for aggressive
      platinum-based chemotherapy, the standard medical treatment for advanced NSCLC.
      With the current evidence, in clinical practice, single-agent chemotherapy with a
      third-generation drug (vinorelbine, gemcitabine, taxanes) should be the
      recommended option for non-selected elderly patients with advanced NSCLC. 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, feasibility of platinum-based
      chemotherapy remains an open issue and has to be proven in prospective randomised
      trials. High priority should be also given to the evaluation of the role of new
      targeted therapies. Moreover, a comprehensive geriatric assessment for
      individualized treatment choice in NSCLC elderly patients is mandatory.

PMID- 16608985
TI  - Multi-target inhibitors in non-small cell lung cancer (NSCLC).

PMID- 16608987
TI  - Chemo-radiotherapy in lung cancer: state of the art with focus on the elderly
      population.

PMID- 16608988
TI  - Extensive small cell lung cancer: standard and experimental treatment approaches
      in elderly patients.

PMID- 16608989
TI  - Maintenance chemotherapy in non-small cell lung cancer.

PMID- 16608990
TI  - Treatment and prophylaxis for brain metastases from non-small cell lung cancer:
      whole brain radiation treatment versus stereotactic radiosurgery.

PMID- 16608991
TI  - Brain metastases in patients with non-small cell lung cancer: focus on the role
      of chemotherapy.

PMID- 16608992
TI  - Prophylactic cranial irradiation in non-small cell lung cancer.

PMID- 16608993
TI  - Women and lung cancer.

PMID- 16608994
TI  - Treatment of advanced non-small cell lung cancer: chemotherapy with or without
      cisplatin?

PMID- 16608995
TI  - The new drugs advent: clinical or economic outcomes?

PMID- 16608996
TI  - Bisphosphonates and metastatic bone disease.

PMID- 16608997
TI  - New antiemetic drugs.
AB  - BACKGROUND: Important progress in the prophylaxis of chemotherapy-induced acute
      and delayed emesis has been achieved but some fundamental needs still remain that
      requires new, efficacious antiemetic drugs. METHODS: A critical review of the
      results of published studies of aprepitant, a new NK1 receptor antagonist, and of
      palonosetron, a 5-HT3 receptor antagonist with a longer half-life. RESULTS:
      Aprepitant combined with dexamethasone and a 5-HT3 antagonist significantly
      increased the control of acute emesis with respect to dexamethasone and a 5-HT3
      antagonist alone after cisplatin and moderately emetogenic chemotherapy. For
      cisplatin nausea, aprepitant combined with dexamethasone significantly increased
      the control of delayed emesis with respect to dexamethasone alone, while for
      moderately emetogenic chemotherapy aprepitant is superior to a 5-HT3 antagonist
      in the control of delayed emesis. Palonosetron showed superior or similar
      efficacy to ondansetron and dolasetron in patients submitted to moderately
      emetogenic chemotherapy and similar efficacy to ondansetron in patients submitted
      to cisplatin. CONCLUSIONS: More studies are necessary comparing aprepitant alone
      or combined with dexamethasone with respect to the recommended antiemetic drugs
      for the prevention of delayed emesis induced by cisplatin and moderately
      emetogenic chemotherapy as well as for palonosetron combined with dexamethasone
      with respect to other 5-HT3 antagonists combined with dexamethasone.

PMID- 16608998
TI  - What's Ub chain linkage got to do with it?
AB  - Ubiquitination-the covalent conjugation of ubiquitin (Ub) to other cellular
      proteins-regulates a wide range of cellular processes. Often, multiple Ub
      molecules are added to the substrate to form a Ub chain. Distinct outcomes have
      been observed for substrates modified with multi-Ub chains linked through
      particular lysine residues. However, recent studies suggest that Ub chain
      linkages may not be the key determinant for substrate fate. Here, we review
      evidence suggesting that Ub-binding proteins play a pivotal role in determining
      the outcome of substrate ubiquitination. In fulfilling their functions in
      proteasome-mediated proteolysis or signaling, Ub receptors link ubiquitinated
      proteins to downstream molecules through protein-protein interactions. Studies of
      Ub-binding factors may therefore hold the key to understanding the diverse
      functions of the Ub molecule.

PMID- 16608999
TI  - An essay on rearranging the deck chairs: what's wrong with the cancer trials
      system?

PMID- 16609000
TI  - Identifying sources of interindividual pharmacokinetic variability with
      population modeling.

PMID- 16609001
TI  - Genomic testing for sensitivity of breast cancer to hormonal therapy.

PMID- 16609002
TI  - Cancer treatment and the older patient.

PMID- 16609003
TI  - Potential of immuno-positron emission tomography for tumor imaging and
      immunotherapy planning.

PMID- 16609004
TI  - A matter of life or death (or both): understanding autophagy in cancer.

PMID- 16609005
TI  - Phase II clinical trial design: methods in translational research from the
      Genitourinary Committee at the Eastern Cooperative Oncology Group.
AB  - Given the increase in novel agents and difficulty with planning and completing
      many phase III studies, various phase II trial design options should be
      considered to more effectively guide phase III trial plans. The need for novel
      phase II trial designs has increased, given the number of novel molecular
      targeted therapies now available for testing, an abundance of cytostatic agents,
      and limited resources to conduct phase III studies for all interesting agents or
      combinations. This review will focus on options for phase II trial designs. We
      review randomized phase II designs with placebo control, randomized selection
      designs, and randomized discontinuation designs. As agents become available for
      testing in the clinic, the strengths and weaknesses of different phase II trial
      designs should be considered to optimize a trial development plan that guides
      phase III trial decisions more effectively.

PMID- 16609006
TI  - Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic
      target in patients with glioblastoma multiforme.
AB  - PURPOSE: More brain tumor markers are required for prognosis and targeted
      therapy. We have identified and validated promising molecular therapeutic
      glioblastoma multiforme (GBM) targets: human transmembrane glycoprotein
      nonmetastatic melanoma protein B (GPNMB(wt)) and a splice variant form
      (GPNMB(sv), a 12-amino-acid in-frame insertion in the extracellular domain).
      EXPERIMENTAL DESIGN: We have done genetic and immunohistochemical evaluation of
      human GBM to determine incidence, distribution, and pattern of localization of
      GPNMB antigens in brain tumors as well as survival analyses. RESULTS:
      Quantitative real-time PCR on 50 newly diagnosed GBM patient tumor samples
      indicated that 35 of 50 GBMs (70%) were positive for GPNMB(wt+sv) transcripts and
      15 of 50 GBMs (30%) were positive for GPNMB(sv) transcripts. Normal brain samples
      expressed little or no GPNMB mRNA. We have isolated and characterized an anti
      GPNMB polyclonal rabbit antiserum (2640) and two IgG2b monoclonal antibodies
      (mAb; G11 and U2). The binding affinity constants of the mAbs ranged from 0.27 x
      10(8) to 9.6 x 10(8) M(-1) measured by surface plasmon resonance with immobilized
      GPNMB, or 1.7 to 2.1 x 10(8) M(-1) by Scatchard analyses with cell-expressed
      GPNMB. Immunohistochemical analysis detected GPNMB in a membranous and
      cytoplasmic pattern in 52 of 79 GBMs (66%), with focal perivascular reactivity in
      approximately 27%. Quantitative flow cytometric analysis revealed GPNMB cell
      surface molecular density of 1.1 x 10(4) to 7.8 x 10(4) molecules per cell,
      levels sufficient for mAb targeting. Increased GPNMB mRNA levels correlated with
      elevated GPNMB protein expression in GBM biopsy samples. Univariate and
      multivariate analyses correlated expression of GPNMB with survival of 39 GBM
      patients using RNA expression and immunohistochemical data, establishing that
      patients with relatively high mRNA GPNMB transcript levels (wt+sv and wt), >3
      fold over normal brain, as well as positive immunohistochemistry, have a
      significantly higher risk of death (hazard ratios, 3.0, 2.2, and 2.8,
      respectively). CONCLUSIONS: Increased mRNA and protein levels in GBM patient
      biopsy samples correlated with higher survival risk; as a detectable surface
      membrane protein in glioma cells, the data indicate that GPNMB is a potentially
      useful tumor-associated antigen and prognostic predictor for therapeutic
      approaches with malignant gliomas or any malignant tumor that expresses GPNMB.

PMID- 16609007
TI  - Delineation, functional validation, and bioinformatic evaluation of gene
      expression in thyroid follicular carcinomas with the PAX8-PPARG translocation.
AB  - A subset of follicular thyroid carcinomas contains a balanced translocation,
      t(2;3)(q13;p25), that results in fusion of the paired box gene 8 (PAX8) and
      peroxisome proliferator-activated receptor gamma (PPARG) genes with concomitant
      expression of a PAX8-PPARgamma fusion protein, PPFP. PPFP is thought to
      contribute to neoplasia through a mechanism in which it acts as a dominant
      negative inhibitor of wild-type PPARgamma. To better understand this type of
      follicular carcinoma, we generated global gene expression profiles using DNA
      microarrays of a cohort of follicular carcinomas along with other common thyroid
      tumors and used the data to derive a gene expression profile characteristic of
      PPFP-positive tumors. Transient transfection assays using promoters of four genes
      whose expression was highly associated with the translocation showed that each
      can be activated by PPFP. PPFP had unique transcriptional activities when
      compared with PAX8 or PPARgamma, although it had the potential to function in
      ways qualitatively similar to PAX8 or PPARgamma depending on the promoter and
      cellular environment. Bioinformatics analyses revealed that genes with increased
      expression in PPFP-positive follicular carcinomas include known PPAR target
      genes; genes involved in fatty acid, amino acid, and carbohydrate metabolism;
      micro-RNA target genes; and genes on chromosome 3p. These results have
      implications for the neoplastic mechanism of these follicular carcinomas.

PMID- 16609008
TI  - Coengagement of CD16 and CD94 receptors mediates secretion of chemokines and
      induces apoptotic death of naive natural killer cells.
AB  - Down-modulation of CD16 (FcgammaRIII) receptors and loss of natural killer (NK)
      cell function have been observed in oral cancer patients. However, neither the
      mechanisms nor the significance of the decrease in CD16 receptors have been fully
      understood. The cytotoxic activity and survival of NK cells are negatively
      regulated by antibodies directed against CD16 surface receptor. The addition of
      anti-CD94 antibody in combination with either F(ab')(2) fragment or intact anti
      CD16 antibody to NK cells resulted in significant inhibition of NK cell cytotoxic
      function and induction of apoptosis in resting human peripheral blood NK cells.
      Addition of interleukin-2 to anti-CD16 and/or anti-CD94 antibody-treated NK cells
      significantly inhibited apoptosis and increased the function of NK cells. There
      was a significant increase in tumor necrosis factor-alpha (TNF-alpha) but not IFN
      gamma secretion in NK cells treated either with anti-CD16 antibody alone or in
      combination with anti-CD94 antibodies. Consequently, the addition of anti-TNF
      alpha antibody partially inhibited apoptosis of NK cells mediated by the
      combination of anti-CD94 and anti-CD16 antibodies. Increase in apoptotic death of
      NK cells also correlated with an increase in type 2 inflammatory cytokines and in
      the induction of chemokines. Thus, we conclude that binding of antibodies to CD16
      and CD94 NK cell receptors induces death of the NK cells and signals for the
      release of chemokines.

PMID- 16609009
TI  - Altered nuclear receptor corepressor expression attenuates vitamin D receptor
      signaling in breast cancer cells.
AB  - PURPOSE: We hypothesized that deregulated corepressor actions, with associated
      histone deacetylation activity, epigenetically suppressed vitamin D receptor
      (VDR) responsiveness and drives resistance towards 1alpha,25-dihydroxyvitamin
      D(3). EXPERIMENTAL DESIGN: Profiling, transcriptional, and proliferation assays
      were undertaken in 1alpha,25(OH)(2)D(3)-sensitive MCF-12A nonmalignant breast
      epithelial cells, a panel of breast cancer cell lines, and a cohort of primary
      breast cancer tumors (n = 21). RESULTS: Elevated NCoR1 mRNA levels correlated
      with suppressed regulation of VDR target genes and the ability of cells to
      undergo arrest in G(1) of the cell cycle. A similar increased ratio of
      corepressor mRNA to VDR occurred in matched primary tumor and normal cells,
      noticeably in estrogen receptor alpha-negative (n = 7) tumors.
      1alpha,25(OH)(2)D(3) resistance in cancer cell lines was targeted by cotreatments
      with either 1alpha,25(OH)(2)D(3) or a metabolically stable analogue (RO-26-2198)
      in combination with either trichostatin A (TSA; histone deacetylation inhibitor)
      or 5-aza-2'-deoxycytidine (DNA methyltransferase inhibitor). Combinations of
      vitamin D(3) compounds with TSA restored VDR antiproliferative signaling (target
      gene regulation, cell cycle arrest, and antiproliferative effects in liquid
      culture) to levels which were indistinguishable from MCF-12A cells. CONCLUSIONS:
      Increased NCoR1 mRNA is a novel molecular lesion in breast cancer cells, which
      acts to suppress responsiveness of VDR target genes, resulting in
      1alpha,25(OH)(2)D(3) resistance and seems to be particularly associated with
      estrogen receptor negativity. This lesion provides a novel molecular diagnostic
      and can be targeted by combinations of vitamin D(3) compounds and low doses of
      TSA.

PMID- 16609010
TI  - Differentially regulated micro-RNAs and actively translated messenger RNA
      transcripts by tumor suppressor p53 in colon cancer.
AB  - PURPOSE: The aim of this study was to investigate the role of p53 in regulating
      micro-RNA (miRNA) expression due to its function as a transcription factor. In
      addition, p53 may also affect other cellular mRNA gene expression at the
      translational level either via its mediated miRNAs or due to its RNA-binding
      function. EXPERIMENTAL DESIGN: The possible interaction between p53 and miRNAs in
      regulating gene expression was investigated using human colon cancer HCT-116 (wt
      p53) and HCT-116 (null-p53) cell lines. The effect of p53 on the expression of
      miRNAs was investigated using miRNA expression array and real-time quantitative
      reverse transcription-PCR analysis. RESULTS: Our investigation indicated that the
      expression levels of a number of miRNAs were affected by wt-p53. Down-regulation
      of wt-p53 via small interfering RNA abolished the effect of wt-p53 in regulating
      miRNAs in HCT-116 (wt-p53) cells. Global sequence analysis revealed that over 46%
      of the 326 miRNA putative promoters contain potential p53-binding sites,
      suggesting that some of these miRNAs were potentially regulated directly by wt
      p53. In addition, the expression levels of steady-state total mRNAs and actively
      translated mRNA transcripts were quantified by high-density microarray gene
      expression analysis. The results indicated that nearly 200 cellular mRNA
      transcripts were regulated at the posttranscriptional level, and sequence
      analysis revealed that some of these mRNAs may be potential targets of miRNAs,
      including translation initiation factor eIF-5A, eIF-4A, and protein phosphatase
      1. CONCLUSION: To the best of our knowledge, this is the first report
      demonstrating that wt-p53 and miRNAs interact in influencing gene expression and
      providing insights of how p53 regulates genes at multiple levels via unique
      mechanisms.

PMID- 16609011
TI  - Inhibition of phosphotyrosine phosphatase 1B causes resistance in BCR-ABL
      positive leukemia cells to the ABL kinase inhibitor STI571.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of BCR-ABL
      mediated transformation in vitro and in vivo. To investigate whether PTP1B
      modulates the biological effects of the abl kinase inhibitor STI571 in BCR-ABL
      positive cells, we transfected Philadelphia chromosome-positive (Ph+) chronic
      myeloid leukemia cell-derived K562 cells with either wild-type PTP1B
      (K562/PTP1B), a substrate-trapping dominant-negative mutant PTP1B (K562/D181A),
      or empty vector (K562/mock). Cells were cultured with or without STI571 and
      analyzed for its effects on proliferation, differentiation, and apoptosis. In
      both K562/mock and K562/PTP1B cells, 0.25 to 1 mumol/L STI571 induced dose
      dependent growth arrest and apoptosis, as measured by a decrease of cell
      proliferation and an increase of Annexin V-positive cells and/or of cells in the
      sub-G(1) apoptotic phase. Western blot analysis showed increased protein levels
      of activated caspase-3 and caspase-8 and induction of poly(ADP-ribose) polymerase
      cleavage. Low concentrations of STI571 promoted erythroid differentiation of
      these cells. Conversely, K562/D181A cells displayed significantly lower PTP1B
      specific tyrosine phosphatase activity and were significantly less sensitive to
      STI571-induced growth arrest, apoptosis, and erythroid differentiation.
      Pharmacologic inhibition of PTP1B activity in wild-type K562 cells, using bis(N,N
      dimethylhydroxamido)hydroxooxovanadate, attenuated STI571-induced apoptosis.
      Lastly, comparison of the STI571-sensitive Ph+ acute lymphoblastic leukemia cell
      line SupB15 with a STI571-resistant subline revealed significantly decreased
      PTP1B activity and enhanced BCR-ABL phosphorylation in the STI571-resistant
      SupB15 cells. In conclusion, functional PTP1B is involved in STI571-induced
      growth and cell cycle arrest, apoptosis, and differentiation, and attenuation of
      PTP1B function may contribute to resistance towards STI571.

PMID- 16609012
TI  - Reversal of the malignant phenotype of cervical cancer CaSki cells through adeno
      associated virus-mediated delivery of HPV16 E7 antisense RNA.
AB  - Human papillomavirus (HPV) infection is the most important risk factor for the
      development of cervical cancer. The oncogene E7 from high-risk HPV strains has
      the ability to immortalize epithelial cells and increase cellular transformation
      in culture. In this study, we explored the possibility of preventing cervical
      cancer growth by inhibiting HPV16 E7 expression through gene transfer of an
      antisense construct. A recombinant adeno-associated virus (rAAV) vector was
      chosen for the transfer, based on its transfection efficiency, in vivo stability,
      and lack of detectable pathology. In vitro transfer of an rAAV vector expressing
      antisense HPV16 E7 (AAV-HPV16E7AS) inhibited cell proliferation, induced
      apoptosis, reduced cell migration, and restrained in vivo proliferation of
      HPV16/HPV18-positive cervical cancer CaSki cells. These results indicate that
      down-regulation of HPV16 E7 with antisense RNA is beneficial in reducing the
      tumorigenicity of CaSki cells, and rAAV vectors ought to be a new efficient
      approach for delivering the expression of therapeutic genes.

PMID- 16609013
TI  - Physiologic levels of 2-methoxyestradiol interfere with nongenomic signaling of
      17beta-estradiol in human breast cancer cells.
AB  - PURPOSE: The purpose of this investigation is to determine the effects of
      physiologic levels (10-50 nmol/L) of 2-methoxyestradiol (2ME) on the growth of
      estrogen receptor (ER)-positive breast cancer cells and provide insights into its
      mechanism(s) of action. EXPERIMENTAL DESIGN: Using the ERalpha-positive breast
      cancer cells, we studied the effects of 2ME on cell proliferation and cell
      signaling. Our hypothesis is that 17beta-estradiol (E(2)) and 2ME can affect
      shared cell signaling pathways, leading to different outcomes in cell
      proliferation, depending on the absence/presence of E(2). RESULTS: E(2)
      stimulated the growth of MCF-7 and T-47 D cells and induced Akt phosphorylation,
      a nongenomic signaling pathway. In the absence of E(2), 10 to 50 nmol/L of 2ME
      enhanced cell growth and Akt phosphorylation. However, in the presence of E(2),
      2ME inhibited E(2)-induced cell growth and prevented E(2)-induced Akt
      phosphorylation. Confocal microscopic studies showed that 2ME inhibited
      subcellular distribution of ERalpha in response to E(2) in MCF-7 and T-47D cells.
      2ME also down-regulated E(2)-induced increases in cyclic AMP and ornithine
      decarboxylase activity. In addition, treatment of MCF-7 cells with 2ME in the
      presence of E(2) resulted in a decrease in ERalpha level by 72 hours. Accelerated
      down-regulation of ERalpha may contribute to growth inhibition in the presence of
      E(2)/2ME combinations. In contrast, a concentration of up to 2.5 mumol/L 2ME had
      no effect on the growth of ER-negative SK-BR-3 cells, either in the presence or
      absence of E(2). CONCLUSIONS: Our results provide evidence for the nongenomic
      action of 2ME in ER-positive cells. In the presence of E(2), 2ME suppressed E(2)
      induced cell growth, Akt signaling, and generation of cyclic AMP, whereas it
      acted as an estrogen in the absence of E(2). The intriguing growth-stimulatory
      and growth-inhibitory effects of 2ME on breast cancer cells suggests the need for
      its selective use in patients.

PMID- 16609014
TI  - Pediatric cancers are infiltrated predominantly by macrophages and contain a
      paucity of dendritic cells: a major nosologic difference with adult tumors.
AB  - PURPOSE: Adult cancer is frequently preceded by a period of prolonged chronic
      inflammation caused by infectious microbial agents or physical or chemical
      irritants. By contrast, an association between the classic pediatric neoplasias
      and inflammatory triggers is only rarely recognized. We hypothesized that the
      difference could be reflected in the inflammatory cell infiltrates of pediatric
      and adult cancer. EXPERIMENTAL DESIGN: Three investigators retrospectively
      studied 27 pediatric and 13 adult cancers at first diagnosis by
      immunohistochemistry. Inflammatory cells were identified and counted, and their
      location in relation to tumor tissue was analyzed. RESULTS: A majority of tumor
      associated leukocytes (TAL) in adult tumors were located at the edges of tumor
      islands forming inflammatory foci between the supporting stroma and the malignant
      infiltrate. In contrast, TALs in pediatric tumors were scattered within the
      malignant tumor islands. In adult tumors, TALs were composed of diverse leukocyte
      types; but in pediatric tumors, the infiltrating cells were predominantly
      macrophages that accumulated in areas of necrosis within the tumors. The most
      striking feature in the pediatric tumors was the virtual absence of dendritic
      cells. The proportion of intratumoral dendritic cells in pediatric samples was
      4.1%; whereas in adult tumors, they formed 36.9% of TALs within the tumor islands
      and 25.1% around the tumors. CONCLUSIONS: We conclude that TALs in pediatric
      cancers are composed mainly of macrophages and largely devoid of dendritic cell.
      The findings may provide a major nosologic difference reclassifying pediatric and
      adult tumors based on nominal inflammatory and noninflammatory etiologies.

PMID- 16609015
TI  - Celecoxib up-regulates the expression of the zeta chain of T cell receptor
      complex in tumor-infiltrating lymphocytes in human cervical cancer.
AB  - PURPOSE: We evaluated the effects of celecoxib treatment on tumor-infiltrating
      lymphocyte (TIL) subsets [CD3(+), CD4(+),CD8(+), CD25(+), and T cell receptor
      (TCR)-zeta-expressing cells] and tryptase-positive mast cells in cervical tumors.
      Circulating levels of cytokines [interleukin (IL)-1beta, IL-10, tumor necrosis
      factor-alpha, IL-6, and IL-12] and angiogenesis-modulating factors (vascular
      endothelial growth factor and endostatin) have also been analyzed. EXPERIMENTAL
      DESIGN: Cervical tumor biopsies and blood samples were obtained at the time of
      diagnosis and after 10 days of celecoxib treatment (400 mg b.i.d., at 8:00 a.m.
      and 8:00 p.m.) in 27 cases. Immunohistochemistry and ELISA assays were used to
      assess the expression of biological factors in tumor tissue and circulating
      levels of cytokines and angiogenic molecules. RESULTS: We showed a statistically
      significant increase in the percentage of TIL expressing the TCR-zeta chain after
      celecoxib treatment: indeed, in cases exposed to celecoxib, the percentage of TCR
      zeta(+) cells ranged from 5.0 to 50.0 (median, 22.5) with respect to baseline
      expression (range, 3.0-50.0; median, 10.0; P = 0.0016). There was no significant
      treatment-related difference in the percentage of CD3(+), CD4(+), CD8(+), and
      CD25(+) TIL as well as in tryptase-positive cells. IL-12 levels were
      significantly reduced in posttreatment samples with respect to baseline levels (P
      = 0.002). We also found a reduction in the circulating levels of vascular
      endothelial growth factor, and a statistically significant increase of serum
      endostatin levels (P = 0.035). CONCLUSIONS: We reported the first evidence in
      humans that celecoxib restores zeta expression by TIL in primary cervical tumors,
      suggesting that a positive modulation of immune function may serve as an
      additional mechanism supporting the antitumor effect of this class of drugs.

PMID- 16609016
TI  - Ribosomal protein l19 is a prognostic marker for human prostate cancer.
AB  - Microquantity differential display analysis of gene expression profiles between
      benign (PNT2) and malignant (PC3M) human prostate cell lines identified the gene
      encoding ribosomal protein L19 (RPL19) to be overexpressed in the malignant
      cells. Northern blot hybridization analysis done on a wide range of human cell
      lines and tissues confirmed the level of RPL19 mRNA to be 5-fold higher in
      malignant cell lines and 8-fold higher in malignant tissues, when compared with
      their benign counterparts. Analysis of RPL19 mRNA expression by in situ
      hybridization revealed a significant increase of RPL19 expression in a
      substantial number of prostate cancers. All of the eight normal prostatic tissues
      were unstained (100%). Of 32 benign prostatic hyperplasia (BPH) tissues, 15
      (46.9%) were unstained, 9 (28.1%) stained weakly, and 8 (25%) stained moderately.
      Among 87 carcinomas, only 7 (8.1%) were unstained, whereas 22 (25.2%) stained
      weakly, 21 (24.1%) stained moderately, and 37 (42.61%) stained strongly. The
      intensity of staining of the malignant specimens was significantly higher than
      that of normal and BPH specimens (chi(2): n = 127, P < 0.001). Gleason scores of
      the carcinomas correlated with RPL19 expression (chi(2): n = 87, P < 0.001).
      Kaplan-Meier survival analysis confirmed increased RPL19 expression to be highly
      predictive of shorter patient survival (P < 0.05), revealing RPL19 to be a
      sensitive predictor of prostate cancer progression. Expression of this protein
      could be a valuable marker in prostate cancer diagnosis and patient management.

PMID- 16609017
TI  - Quantitative analysis of human telomerase reverse transcriptase in pancreatic
      cancer.
AB  - Although telomerase activity is a promising diagnostic marker, clinical
      introduction of this marker for cancer diagnosis is still problematic due to the
      lack of means of evaluating sample quality. Human telomerase reverse
      transcriptase (hTERT), one of the subunits of telomerase, is also a promising
      diagnostic marker. In the present study, we did large-scale analysis of 88
      pancreatic juice samples to determine the feasibility of quantitative analysis of
      hTERT mRNA for diagnosis of pancreatic cancer. We found significant differences
      in hTERT expression among carcinoma-derived, intraductal papillary mucinous
      neoplasm (IPMN)-derived, and chronic pancreatitis-derived juice samples. Results
      showed that quantitative analyses of hTERT mRNAs are more useful in
      discriminating carcinoma from IPMN than from chronic pancreatitis. When the
      specificity was set at 100%, the sensitivity for differentiation between
      carcinoma and IPMN was 43.5%, whereas the sensitivity of cytologic examination
      was 22.0%. There were significant differences in hTERT expression among carcinoma
      cells, IPMN cells, and normal ductal cells isolated from pancreatic tissues by
      microdissection. Lymphocytes and hyperplastic epithelial cells isolated from
      tissues with the histologic appearance of pancreatitis showed various expression
      levels of hTERT. Our results suggest that quantitative analysis of hTERT mRNA in
      pancreatic juice is advantageous over cytologic analysis for differentiation
      between carcinoma and IPMN but probably not for differentiation between carcinoma
      and chronic pancreatitis.

PMID- 16609018
TI  - Identification of gains on 1q and epidermal growth factor receptor overexpression
      as independent prognostic markers in intracranial ependymoma.
AB  - PURPOSE: Pathogenesis of ependymomas is still poorly understood and molecular
      markers for risk-adapted patient stratification are not available. Our aim was to
      screen for novel genomic imbalances and prognostic markers in ependymal tumors.
      EXPERIMENTAL DESIGN: We analyzed 68 sporadic tumors by matrix-based comparative
      genomic hybridization using DNA microarrays containing >6,400 genomic DNA
      fragments. Novel recurrent genomic gains were validated by fluorescence in situ
      hybridization using a tissue microarray consisting of 170 intracranial
      ependymomas. Candidate genes were also tested for mRNA expression by quantitative
      real-time PCR, and protein expression was determined by immunohistochemistry on
      the tissue microarray. RESULTS: Chromosomal gain of 1q correlated with pediatric
      patients (P = 0.004), intracranial ependymomas (P = 0.05), and tumors of grade
      III (P = 0.002). Gain of 1q21.1-32.1 was associated with tumor recurrence in
      intracranial ependymomas (P < 0.001). Furthermore, gain of 1q25 as determined by
      fluorescence in situ hybridization represented an independent prognostic marker
      for either recurrence-free survival (P < 0.001) or overall survival (P = 0.003).
      Recurrent gains at 5p15.33 covering hTERT were validated by immunohistochemistry,
      and elevated protein levels correlated with adverse prognosis (P = 0.01). In
      addition to frequent gains and high-level amplification of epidermal growth
      factor receptor (EGFR) at 7p11.2, immunohistochemistry revealed protein
      overexpression to be correlated with poor prognosis (P = 0.002). EGFR protein
      status subdivides intracranial grade II ependymomas into two different risk
      groups (P = 0.03) as shown by multivariate analysis. CONCLUSIONS: Thus, the
      states of 1q25 and EGFR represent independent prognostic markers for intracranial
      ependymomas to identify patient subgroups with different risk profiles in further
      clinical investigations. Moreover, EGFR might serve as therapeutic target for
      more specific chemotherapy applications.

PMID- 16609019
TI  - A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for
      prediction of recurrence and survival in women receiving adjuvant tamoxifen.
AB  - PURPOSE: In the adjuvant treatment of estrogen receptor (ER)-positive breast
      cancer, additional markers are needed to identify women at high risk for
      recurrence. EXPERIMENTAL DESIGN: We examined the association between the ratio of
      the homeobox 13 (HOXB13) to interleukin-17B receptor (IL-17BR) expression and the
      clinical outcomes of relapse and survival in women with ER-positive breast cancer
      enrolled onto a North Central Cancer Treatment Group adjuvant tamoxifen trial
      (NCCTG 89-30-52). RESULTS: Tumor blocks were obtained from 211 of 256 eligible
      patients, and quantitative reverse transcription-PCR profiles for HOXB13 and IL
      17BR were obtained from 206 patients. The cut point for the two-gene log
      2(expression ratio) that best discriminated clinical outcome (recurrence and
      survival) was selected and identified women with significantly worse relapse-free
      survival (RFS), disease-free survival (DFS), and overall survival (OS),
      independent of standard prognostic markers. The cut point differed as a function
      of nodal status [node negative (59th percentile) versus node positive (90th
      percentile)]. In the node-positive cohort (n = 86), the HOXB13/IL-17BR ratio was
      not associated with relapse or survival. In contrast, in the node-negative cohort
      (n = 130), a high HOXB13/IL-17BR ratio was associated with significantly worse
      RFS [hazard ratio (HR), 1.98; P = 0.031], DFS (HR, 2.03; P = 0.015), and OS (HR,
      2.4; P = 0.014), independent of standard prognostic markers. CONCLUSION: A high
      HOXB13/IL-17BR expression ratio is associated with increased relapse and death in
      patients with resected node-negative, ER-positive breast cancer treated with
      tamoxifen and may identify patients in whom alternative therapies should be
      studied.

PMID- 16609020
TI  - Messenger RNA expression of leptin and leptin receptors and their prognostic
      value in 322 human primary breast cancers.
AB  - PURPOSE: Leptin and obesity are clearly related, and obesity is associated with
      an increased risk of breast cancer. We therefore measured the expression of
      leptin and its two main receptor isoforms, OBR-L and OBR-S, in 322 breast
      cancers. We analyzed their relations with the classical prognostic factors and
      with survival to establish their links with breast cancer. EXPERIMENTAL DESIGN:
      The expression of leptin and its receptors was quantified by real-time reverse
      transcription-PCR, using TaqMan fluorogenic probes and an ABI PRISM 7700 sequence
      detector system (Applied Biosystems, Courtaboeuf, France). TATA box binding
      protein was used to normalize expression. The human breast cancer cell, SK-BR-3,
      expressing the three targets, was chosen as the calibrator sample (i.e., target
      expression = 1). RESULTS: All the tumors expressed both receptors, and 318 of 322
      expressed leptin. These three variables correlated positively with each other and
      with estradiol and progesterone receptors, whereas they correlated negatively
      with histoprognostic grading and tumor diameter. OBR-L/OBR-S expression was
      inversely correlated with progesterone receptors. Patients with elevated OBR-S
      expression had longer relapse-free survival (P = 0.008), whereas high OBR-L/OBR-S
      was associated with a shorter relapse-free survival (P = 0.05). In Cox
      multivariate analyses, OBR-S maintained its prognostic value (P = 0.02; relative
      risk, 0.51). CONCLUSIONS: This study shows that (a) almost all of the breast
      cancers coexpress leptin and its two main isoforms of receptors, suggesting that
      the human epithelial breast cancer cells respond to leptin acting via an
      autocrine pathway; (b) high expression levels of leptin and leptin receptors are
      biological markers of a more differentiated phenotype; and that (c) OBR-S is an
      independent prognostic factor.

PMID- 16609021
TI  - Thymidylate synthase messenger RNA expression in plasma from patients with colon
      cancer: prognostic potential.
AB  - PURPOSE: Thymidylate synthase (TS), a critical target in fluorouracil-based
      chemotherapy, is a prognostic marker in colon carcinomas and a predictor of
      response to treatment. Tumor RNA has been detected in plasma from cancer patients
      and is associated with poor prognosis. This is the first study to examine
      extracellular TS mRNA in plasma from patients with colon carcinoma, and its
      possible relation with TS promoter enhancer region (TSER) polymorphism.
      EXPERIMENTAL DESIGN: TS expression was measured in plasma from 88 patients and 26
      controls, and in a tumor subgroup of this series by quantitative PCR. Genotyping
      for TSER polymorphism was done in 60 patients. Clinicopathologic variables were
      correlated with these molecular changes. RESULTS: TS mRNA was detected in plasma
      in 47% of patients, showing significant differences from healthy controls.
      Patients with TS mRNA in plasma had higher levels of TS in tumor tissue than
      patients without. The presence of TS mRNA was associated with lymph node
      metastases and more advanced stages. Polymorphism TSER 3/3 was found in 38% of
      cases, and was significantly correlated with high amounts of TS mRNA in plasma.
      CONCLUSIONS: Our results suggest that TS mRNA in plasma originated from tumors,
      it may indicate poor prognosis and might help to classify tumors in Dukes' stages
      B and C. The TSER genotype may influence TS mRNA expression in plasma.

PMID- 16609022
TI  - Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis
      of colorectal cancer.
AB  - OBJECTIVES: We have undertaken a comprehensive study of common polymorphisms in
      genes of DNA repair, exploring both the risk of developing colorectal cancer and
      the prognosis of patients. METHODS: Subjects from a case-control study (377 cases
      and 329 controls) designed to assess gene-environment interactions were genotyped
      by use of an oligonucleotide microarray and the arrayed primer extension
      technique. Twenty-eight single nucleotide polymorphisms in 15 DNA repair genes
      were included. The candidate genes belong to different DNA repair pathways: base
      excision repair (OGG1, LIG3, APEX, POLB, XRCC1, PCNA, and MUTYH), nucleotide
      excision repair (ERCC1, ERCC2, ERCC4, and ERCC5), double-strand breaks repair
      (XRCC2, XRCC3, and XRCC9), and reversion repair (MGMT) genes. RESULTS:
      Polymorphism OGG1 S326C was associated with an increased risk of colorectal
      cancer [odds ratio (OR), 2.3; 95% confidence interval (95% CI), 1.1-5.0], the
      risk being higher in younger individuals. A haplotype of ERCC1 was associated
      with increased risk (OR, 2.3; 95% CI, 1.0-5.3). POLB P242R was also associated
      with decreased risk (OR, 0.23; 95% CI, 0.05-0.99), although the number of variant
      allele carriers was low. In the univariate analysis, adjusted for age, sex, and
      Dukes' stage, three polymorphisms were significantly associated with better
      prognosis: XRCC1 R399Q [hazard ratio (HR), 0.38; 95% CI, 0.17-0.85], XRCC3 T141M
      (HR, 0.66; 95% CI, 0.45-0.97), and MGMT L84F (HR, 0.14; 95% CI, 0.02-0.99). ERCC1
      19007T>C was associated with worse prognosis (HR, 1.51; 95% CI, 1.01-2.27). In a
      multivariate analysis, only XRCC1 R399Q and ERCC1 19007T>C remained significant.
      These associations were stronger among patients receiving adjuvant chemotherapy.
      CONCLUSIONS: Although the overall effect of DNA repair genes in colorectal cancer
      etiology seems limited, their influence in the response to chemotherapy and
      prognosis may be more relevant. This knowledge may help to clarify the utility of
      specific adjuvant treatments according to the individual genetic background.

PMID- 16609023
TI  - Combination analysis of hypermethylated Wnt-antagonist family genes as a novel
      epigenetic biomarker panel for bladder cancer detection.
AB  - PURPOSE: Aberrant promoter hypermethylation of Wnt-antagonist genes contributes
      to the pathogenesis of several cancers. We hypothesized that combined methylation
      analysis of Wnt-antagonist genes could improve their use as a panel of biomarkers
      for diagnosing and staging of bladder cancers. EXPERIMENTAL DESIGN: Samples (54
      total) of bladder tumor and corresponding normal bladder mucosa were analyzed for
      the methylation and expression levels of six Wnt-antagonist genes (sFRP-1, sFRP
      2, sFRP-4, and sFRP-5, Wif-1, and Dkk-3). To increase the sensitivity/specificity
      of bladder tumor detection, the methylation score (M score), a new method for
      multigene methylation analysis, was developed. The M score of each sample was
      calculated as the sum of the corresponding log hazard ratio coefficients derived
      from multivariate logistic regression analysis of the methylation status for each
      Wnt-antagonist gene. Receiver operator characteristic (ROC) curve analysis was
      used to determine the optimal sensitivity/specificity of the M score. Urine DNA
      from 24 matched patients with bladder tumor and 20 cancer-free volunteers was
      also used to investigate the methylation status of Wnt-antagonist genes. RESULTS:
      The methylation levels of Wnt-antagonists were significantly higher and mRNA
      levels were significantly lower in bladder tumor than in bladder mucosa. Each
      methylation level was inversely correlated with the corresponding mRNA level. In
      multivariate regression analysis, the methylation levels of sFRP-2 and Dkk-3 were
      significant independent predictors of bladder tumor (P < 0.05 and P < 0.01,
      respectively), whereas with sFRP-1, sFRP-5, and Wif-1 there was a trend towards
      significance as independent predictors. The M score of Wnt-antagonist genes was
      significantly higher in bladder tumor than in bladder mucosa (P < 0.05). Overall,
      the M score had a sensitivity of 77.2% and a specificity of 66.7% as a diagnostic
      biomarker (areas under the curve, 0.763). The M score could distinguish
      superficial from invasive bladder tumors with a sensitivity of 72.2% and a
      specificity of 61.1% as a staging biomarker (areas under the curve, 0.671). In
      patients with bladder tumor, 80.6% of the methylation-specific PCR results had
      identical methylation in samples of tumor- and urine-derived DNA. Most urine DNA
      in normal controls showed no aberrant methylation of the Wnt-antagonist genes.
      CONCLUSIONS: Hypermethylation of Wnt-antagonist genes plays an important role in
      the pathogenesis of bladder tumor and can be detected using cellular DNA
      extracted from urine samples. This is the first report demonstrating that M score
      analysis of Wnt-antagonist genes could serve as an excellent epigenetic biomarker
      panel for bladder tumors.

PMID- 16609024
TI  - Bead-based ELISA for validation of ovarian cancer early detection markers.
AB  - PURPOSE: Efforts to validate ovarian cancer early detection biomarkers with
      immunoassays are challenged by the limited specimen volumes available. We sought
      to develop a specimen-efficient assay to measure CA125 in serum, assess its
      reproducibility, validity, and performance, and test its potential for
      multiplexing and combining with human epididymis protein 4 (HE4), a promising
      novel ovarian cancer marker. EXPERIMENTAL DESIGN: Four pairs of commercially
      available anti-CA125 antibodies and one pair of anti-HE4 antibodies were
      evaluated for accuracy in measuring known concentrations of antigen on a bead
      based platform. The two best pairs were further assessed for reproducibility,
      validity, and the ability to discriminate between blinded serum samples obtained
      from ovarian cancer cases (n = 66) and women without ovarian cancer (n = 125).
      RESULTS: Suitability for use in a bead-based assay varied across CA125 antibody
      pairs. Two CA125 bead-based assays were highly reproducible (overall correlations
      between replicates >/= 0.95; coefficients of variation < 0.2) and strongly
      correlated with the research standard CA125II RIA (correlations >/= 0.9). Their
      ability to distinguish ovarian cancer cases from non-cases based on receiver
      operating characteristic analyses (area under the curve, AUC, of 0.85 and 0.84)
      was close to that of the CA125II RIA (AUC, 0.87). The HE4 bead-based assay showed
      lower reproducibility but yielded an AUC of 0.89 in receiver operating
      characteristics analysis. Multiplexing was not possible but a composite marker
      including CA125 and HE4 achieved an AUC of 0.91. CONCLUSION: Optimization
      procedures yielded two bead-based assays for CA125 that perform comparably to the
      standard CA125II RIA, which could be combined with an HE4 bead-based assay to
      improve diagnostic performance, and requires only 15 muL of sample each.

PMID- 16609025
TI  - Diffuse large B-cell lymphoma with overexpression of cyclin e substantiates poor
      standard treatment response and inferior outcome.
AB  - PURPOSE: Gold standard to predict survival and stratify patients for risk-adapted
      therapy in diffuse large B-cell lymphoma (DLBCL) is the international prognostic
      index, although it does not consider the molecular heterogeneity of DLBCL.
      Deregulation of cyclin E (CCNE) is a strong predictor of poor prognosis in some
      neoplastic diseases. In tumor cells, it induces chromosomal instability with an
      increased rate of aneuploidy/polyploidy. EXPERIMENTAL DESIGN: We analyzed in this
      retrospective study the prognostic value of immunohistochemical CCNE expression
      on a validated tissue microarray containing 101 de novo DLBCLs and, in 9 cases,
      the CCNE-induced chromosomal instability as assessed by cytometry. RESULTS: Forty
      six of 98 evaluable DLBCLs expressed CCNE in a mean proportion of 20 +/- 29% of
      tumor cells; 38 cases expressed CCNE in >/=20% of tumor cells. CCNE-positive
      samples were aneuploid compared with near tetraploidy in CCNE-negative cases.
      Multivariate analysis showed CCNE expression in >/=20% of tumor cells to be an
      international prognostic index-independent, Adriamycin-based treatment
      independent, and BCL2-independent prognostic factor for poor disease-specific
      survival. CCNE expression in >/=80% of tumor cells was associated with dismal
      short-term prognosis. CCNE expression in >/=50% of tumor cells emerged as an
      independent predictive factor for standard CHOP treatment resistance.
      CONCLUSIONS: CCNE expression assessment is easy on paraffin-embedded tissue. The
      high prognostic value of CCNE expression in DLBCL may be the basis for future
      prospective trials. In addition, a high CCNE expression hints at the presence of
      a possible target for individualized cancer therapy.

PMID- 16609026
TI  - Performance of immuno-positron emission tomography with zirconium-89-labeled
      chimeric monoclonal antibody U36 in the detection of lymph node metastases in
      head and neck cancer patients.
AB  - PURPOSE: Immuno-positron emission tomography (PET), the combination of PET with
      monoclonal antibodies (mAb), is an attractive option to improve tumor detection
      and to guide mAb-based therapy. The long-lived positron emitter zirconium-89
      ((89)Zr) has ideal physical characteristics for immuno-PET with intact mAbs but
      has never been used in a clinical setting. In the present feasibility study, we
      aimed to evaluate the diagnostic imaging performance of immuno-PET with (89)Zr
      labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the
      head and neck (HNSCC), who were at high risk of having neck lymph node
      metastases. EXPERIMENTAL DESIGN: Twenty HNSCC patients, scheduled to undergo neck
      dissection with or without resection of the primary tumor, received 75 MBq (89)Zr
      coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by
      computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET
      before surgery. Six patients also underwent PET with (18)F-fluoro-2-deoxy-d
      glucose. Immuno-PET scans were acquired up to 144 hours after injection.
      Diagnostic findings were recorded per neck side (left or right) as well as per
      lymph node level (six levels per side), and compared with histopathologic
      outcome. For this purpose, the CT/MRI scores were combined and the best of both
      scores was used for analysis. RESULTS: Immuno-PET detected all primary tumors (n
      = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity
      72%) and in 11 of 15 positive sides (sensitivity 73%). Interpretation of immuno
      PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25
      operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and
      accuracies of 90% and 80% were found per level and side, respectively. In the six
      patients with seven tumor-involved neck levels and sides, immuno-PET and (18)F
      fluoro-2-deoxy-d-glucose PET gave comparable diagnostic results. CONCLUSION: In
      this study, immuno-PET with (89)Zr-cmAb U36 performed at least as good as CT/MRI
      for detection of HNSCC lymph node metastases.

PMID- 16609027
TI  - Evaluation of adverse events experienced by older patients participating in
      studies of molecularly targeted agents alone or in combination.
AB  - BACKGROUND: The tolerability of molecularly targeted agents in older patients has
      not been specifically examined. Adverse event data from clinical trials in the
      Princess Margaret Hospital Phase II Consortium database were analyzed to address
      this question. METHODS: The Consortium database collects trial information on all
      patients treated with either a molecularly targeted agent alone or in combination
      since 2001. The frequency of adverse events was determined and analyzed by two
      different age groups, <65 years and >/=65 years. Toxicity indices (TI) and
      frequencies of dose-limiting toxicities (DLT), based on adverse events of all
      causalities (TI(ALL) and DLT(ALL)), and on adverse events that were at least
      possibly related to the molecularly targeted agent (TI(MTA) and DLT(MTA)), were
      calculated for both age groups. RESULTS: Four hundred and one patients who
      received 1,252 treatment cycles were analyzed from 19 different studies. Baseline
      performance status was similar between both age groups, but fewer older patients
      have had multiple prior regimens of chemotherapy or prior radiation therapy. A
      comparison of the proportions of younger and older patients experiencing DLT(ALL)
      and DLT(MTA) showed similar results. The TI(MTA) values were comparable between
      the two age groups in both single agent (3.25 versus 3.00, for <65 versus >/=65
      years) and multi-agent (3.65 versus 3.00, for <65 versus >/=65 years) trials.
      CONCLUSIONS: Older patients seem to tolerate molecularly targeted therapies
      either alone or in combination with chemotherapy as well as younger patients. Age
      alone should not be a barrier in the administration of targeted agents.

PMID- 16609028
TI  - Quantitative effect of gender, age, liver function, and body size on the
      population pharmacokinetics of Paclitaxel in patients with solid tumors.
AB  - BACKGROUND: The aim of this study was to quantitatively assess the effect of
      anthropometric and biochemical variables and third-space effusions on paclitaxel
      pharmacokinetics in solid tumor patients. MATERIALS AND METHODS: Plasma
      concentration-time data of paclitaxel were collected in patients with non-small
      cell lung cancer (n = 84), ovarian cancer (n = 40), and various solid tumors (n =
      44), totaling 168 patients. Paclitaxel was given as a 3-hour infusion (n = 163)
      at doses ranging from 100 to 250 mg/m(2), or as a 24-hour infusion (n = 5) at a
      dose of 135 or 175 mg/m(2). Data were analyzed using nonlinear mixed-effect
      modeling. RESULTS: A three-compartment model with saturable elimination and
      distribution was used to describe concentration-time data. Male gender and body
      surface area were positively correlated with maximal elimination capacity of
      paclitaxel (VM(EL)); patient age and total bilirubin were negatively correlated
      with VM(EL) (P < 0.005 for all correlations). Typically, male patients had a 20%
      higher VM(EL); a 0.2 m(2) increase of body surface area led to a 9% increase of
      VM(EL); a 10-year increase of patient age led to a 5% decrease of VM(EL); and a
      10-micromol increase of total bilirubin led to a 14% decrease of VM(EL). Third
      space effusions were not correlated with paclitaxel pharmacokinetics.
      CONCLUSIONS: This extended retrospective population analysis showed patient
      gender to significantly and independently affect paclitaxel distribution and
      elimination. Body surface area, total bilirubin, and patient age were confirmed
      to affect paclitaxel elimination. This pharmacokinetic model allowed
      quantification of the covariate effects on the elimination of paclitaxel and may
      be used for covariate-adapted paclitaxel dosing.

PMID- 16609029
TI  - Population pharmacokinetics of troxacitabine, a novel dioxolane nucleoside
      analogue.
AB  - PURPOSE: To develop and validate a population pharmacokinetic model for
      troxacitabine, a novel l-nucleoside analogue, administered by short infusion; to
      characterize clinical covariates that influence pharmacokinetic variability; and
      to design a dosage rate for continuous infusion administration to achieve low
      micromolar concentrations, which may be more efficacious than shorter infusions.
      EXPERIMENTAL DESIGN: Plasma samples from 111 cancer patients receiving
      troxacitabine (0.12-12.5 mg/m(2)) as a 30-minute infusion in phase I trials were
      used to develop the model with NONMEM. Clinical covariates evaluated included
      creatinine clearance, body surface area, age, and sex. From the model, a
      troxacitabine dosage rate of 2.0 to 3.0 mg/m(2)/d was expected to achieve a
      target concentration of 0.1 micromol/L; plasma samples were obtained during the
      infusion from eight patients receiving troxacitabine as a 3-day infusion.
      RESULTS: Troxacitabine pharmacokinetics were characterized by a three-compartment
      linear model. The mean value for systemic clearance [interindividual variability
      (CV%)] from the covariate-free model was 9.1 L/h (28%). Creatinine clearance and
      body surface area accounted for 36% of intersubject variation in clearance.
      Troxacitabine 2.0 mg/m(2)/d (n = 3) and 3.0 mg/m(2)/d (n = 5) for 3 days produced
      mean +/- SD end of infusion concentrations of 0.12 +/- 0.03 and 0.15 +/- 0.03
      micromol/L, respectively. CONCLUSIONS: Renal function and body surface area were
      identified as sources of troxacitabine pharmacokinetic variability. The
      population pharmacokinetic model model-derived dosage rates for continuous
      infusion administration successfully achieved predetermined target plasma
      concentrations. The present model may be used to optimize treatment with
      troxacitabine by developing a dosing strategy based on both renal function and
      body size.

PMID- 16609030
TI  - Effects of smoking on the pharmacokinetics of erlotinib.
AB  - PURPOSE: To compare the pharmacokinetic variables of erlotinib in current smokers
      with nonsmokers after receiving a single oral 150 or 300 mg dose of erlotinib.
      EXPERIMENTAL DESIGN: This was a single-center, open-label pharmacokinetic study
      in healthy male subjects. Subjects were enrolled into two treatment cohorts based
      on smoking status (current smokers and nonsmokers). The pharmacokinetic profile
      for erlotinib and its metabolite, OSI-420, was determined for each subject
      following each treatment. RESULTS: Current smokers achieved significantly less
      erlotinib exposure following a single 150 or 300 mg dose than nonsmokers.
      Following the 150 mg dose, the geometric mean erlotinib AUC(0-infinity) in
      smokers was 2.8-fold lower than in nonsmokers and similar to that of nonsmokers
      at the 300 mg dose. C(max) in smokers was two-thirds of that in nonsmokers, and
      C(24h) in smokers was 8.3-fold lower than in nonsmokers. The median C(24h) of
      smokers at the 300 mg dose was slightly less than the C(24h) of smokers at the
      150 mg dose. The median C(max) was greater in smokers at the 300 mg dose than in
      nonsmokers at the 150 mg dose. CONCLUSION: This study confirms that the
      pharmacokinetics of erlotinib is different in current smokers and nonsmokers. The
      observation that AUC(0-infinity) and C(24h) were significantly decreased in
      smokers compared with nonsmokers, and a smaller decrease in C(max) was observed,
      is consistent with increased metabolic clearance of erlotinib in current smokers.

PMID- 16609031
TI  - Phase II trial of celecoxib in prostate-specific antigen recurrent prostate
      cancer after definitive radiation therapy or radical prostatectomy.
AB  - OBJECTIVES: Recent evidence has shown that cyclooxygenase-2 (COX-2) inhibitors
      have potent antitumor activity in prostate cancer both in vitro and in vivo.
      However, human trials are absent. This study evaluated the efficacy of the COX-2
      inhibitor celecoxib in prostate-specific antigen (PSA) recurrent prostate cancer
      after radiation therapy (X-ray therapy or XRT) or radical prostatectomy. METHODS:
      Forty patients who had biochemical relapse after XRT or radical prostatectomy
      were treated with celecoxib 400 mg twice per day. Follow-up PSA levels were
      obtained at 3, 6, 12, and 18 months and subsequently every 6 months thereafter.
      Data were evaluated by calculating PSA doubling times and by calculating the
      slope of the curve of log(PSA) versus time to assess rate of PSA increase before
      and after celecoxib treatment for each patient. RESULTS: Thirty-six of 40 (90%)
      patients had a slowing effect on their rate of PSA after 3 months, including 11
      of 40 with a decline and 8 of 40 with stabilization of PSA. Short-term responses
      at 3 months continued at 6, 12, 18 months. Comparison of rate of PSA increase
      before versus after celecoxib treatment showed significant flattening of slope of
      log(PSA) versus time from pretreatment for each of the time points. There was no
      significant change in testosterone levels, suggesting an androgen-independent
      mechanism. CONCLUSIONS: COX-2 inhibitors may have an effect on serum PSA levels
      in patients with biochemical progression after XRT or radical prostatectomy.
      These results suggest that COX-2 inhibitors may help delay or prevent disease
      progression in these patients and thereby help extend the time until androgen
      deprivation therapy.

PMID- 16609032
TI  - Selenium accumulation in prostate tissue during a randomized, controlled short
      term trial of l-selenomethionine: a Southwest Oncology Group Study.
AB  - PURPOSE: Epidemiologic and clinical data suggest that selenium could prevent
      prostate cancer, but it has not been shown that supplemental selenium leads to an
      increased concentration of selenium in prostate tissue compared with adjacent
      tissue. EXPERIMENTAL DESIGN: We conducted a randomized, controlled, short-term
      trial of l-selenomethionine (SeMet) versus observation in men with organ-confined
      prostate cancer. The primary endpoint was the measurement of selenium
      concentration in prostate tissue and seminal vesicle (SV). We assessed baseline
      selenium levels in serum and in toenail specimens (reflecting long-term intake)
      and post-intervention selenium levels in serum, and in prostate and SV tissues
      using hydride generation atomic fluorescence spectroscopy. RESULTS: Sixty-six
      eligible patients were randomly assigned to the SeMet (n = 34) or observation (n
      = 32) arm; both arms had similar baseline patient characteristics. Baseline serum
      selenium was similar in the two groups (P = 0.64). Baseline toenail selenium
      levels were slightly higher in the SeMet group than in the control group (P =
      0.07). After the intervention, the mean serum selenium level increased 15% in the
      SeMet arm and was higher than in the observation arm (P = 0.001). The selenium
      concentration in prostate tissue was 22% higher in the SeMet arm (n = 26) than in
      the observation arm (n = 25; 1.80 versus 1.47 ppm; P = 0.003, Wilcoxon rank sum
      test) and remained significantly higher after adjusting for chronic selenium
      intake (P = 0.021, ANCOVA). SV selenium concentration was similar in both groups
      (P = 0.384) and was lower than in prostate tissue. CONCLUSIONS: The present study
      is the first to show that selenium taken as oral supplementation accumulates
      preferentially in the human prostate gland as opposed to the SV. These findings
      support the hypothesis that oral selenium supplementation may contribute to the
      cancer preventive effects of selenium.

PMID- 16609033
TI  - Carbon beam therapy overcomes the radiation resistance of uterine cervical cancer
      originating from hypoxia.
AB  - PURPOSE: High linear energy transfer (LET) particles are believed to decrease
      tumor radiation resistance originating from hypoxia. However, no proof of this
      effect has been provided by clinical trials and related clinical research. Hence,
      we investigated the radiation biological aspects of high LET carbon beam therapy
      on cervical cancer. EXPERIMENTAL DESIGN: This study involved 49 patients with
      stage IIIb bulky and stage IVa cervical cancer treated with high LET carbon beams
      between October 1995 and June 2000. Oxygen partial pressure (pO(2)) was measured
      by using a needle-type polarographic oxygen electrode. RESULTS: The 4-year
      disease-free survival rates of patients with pO(2) </= 20 mm Hg (hypoxic tumor)
      and pO(2) > 20 mm Hg (oxygenated tumor) before treatment were 37% and 21%,
      respectively. The local control rates of hypoxic and oxygenated tumors before
      treatment were 58% and 54%, respectively. The disease-free survival rates of
      hypoxic and oxygenated tumors assessed by oxygen status at the 5th day of
      irradiation were 33% and 32%, respectively. The local control rates of hypoxic
      and oxygenated tumors at the 5th day were 60% and 58%, respectively. There was no
      significant prognostic difference between hypoxic and oxygenated tumors.
      CONCLUSION: The similar disease-free survival and local control rates between
      hypoxic and oxygenated tumors before and during treatment indicated that the role
      of the tumor oxygenation status was not so important in local control in carbon
      beam therapy. These results indicated that high LET carbon beam irradiation might
      reduce the radiation-resistant nature stemming from tumor hypoxia.

PMID- 16609034
TI  - Low and high tenascin-expressing tumors are efficiently targeted by ST2146
      monoclonal antibody.
AB  - ST2146biot is a biotinylated anti-tenascin monoclonal antibody (mAb) to be used
      for Pretargeted Antibody Guided Radioimmunotherapy (PAGRIT) of solid tumors. In
      vivo biodistribution studies of (125)I-labeled ST2146biot were done in nude mice
      transplanted with human HT-29 colon carcinoma and/or human U-118MG glioblastoma
      cells characterized for low and high tenascin expression, respectively. In vitro
      results show that ST2146 retains immunoreactivity upon biotinylation, in contrast
      to other anti-tenascin mAbs. In vivo biodistribution of ST2146 shows specific
      tumor accumulation up to 10 days after the i.v. injection, with no relevant
      differences between biotinylated and nonbiotinylated ST2146. A dose of 4
      microg/mouse saturates the low tenascin-expressing human colon carcinoma HT-29,
      whereas the high tenascin-expressing human glioblastoma U-118MG seems to be
      saturated at a ST2146biot dose between 320 and 640 microg/mouse. The percentage
      of injected dose per gram of tumor ranges from 10% to 30%, corresponding to an
      amount of ST2146biot/g of tumor of approximately 400 ng/g and >200 microg/g for
      HT-29 and U-118MG, respectively. Tumor to normal organs uptake ratios are between
      15 and 60, confirming high tumor selectivity of ST2146biot despite its cross
      reactivity with the tenascin expressed at low level in the normal mouse organs.
      The ST2146biot localization data are substantially confirmed even when both low
      and high tenascin-expressing tumors are implanted in the same animal. To our
      knowledge, the absolute amount of ST2146biot, specifically localized in
      xenotransplanted human tumors, is the highest thus far described and supports the
      clinical use of this mAb in PAGRIT(R).

PMID- 16609035
TI  - Synergistic antitumor effects of combined epidermal growth factor receptor and
      vascular endothelial growth factor receptor-2 targeted therapy.
AB  - PURPOSE: Combination therapies that target the epidermal growth factor receptor
      (EGFR) and vascular endothelial growth factor receptor (VEGFR) pathways, are
      being actively tested for the treatment of cancer. In evaluating combination
      strategies, the ideal combination would be one in which the treatments interact
      in a way that is synergistic with regard to antitumor effects. Here, we have
      evaluated the interaction between anti-EGFR antibody Erbitux (cetuximab) and anti
      VEGFR2 antibody, DC101, in preclinical models of pancreatic (BxPC-3) and colon
      (GEO) cancer. EXPERIMENTAL DESIGN: Analysis of the interaction between cetuximab
      and DC101 in vivo used a novel method for establishing the upper 95% confidence
      limits for the combination index (CI) of isobologram analyses, where CI < 1
      indicates synergy. Assessment of tumor cell proliferation, apoptosis, VEGF
      production, and hypoxia, as well as tumor vascularization, was performed to gain
      insights into the mechanistic basis for synergy between agents targeting
      different tumor compartments. RESULTS: Monotherapy ED(50) values for tumor growth
      inhibition ranged from 1.8 to 2.3 mg/kg and 10.5 to 16.6 mg/kg for cetuximab and
      DC101, respectively. From the dose response of the combination treatment, it was
      determined that cetuximab and DC101 are synergistic in the BxPC-3 (CI = 0.1, P <
      0.01) and GEO (CI = 0.1, P < 0.01) models. Overlapping effects on the tumor cell
      and vascular compartments form a basis for the interaction, with VEGF production
      and hypoxia-inducible factor 1alpha potentially acting as molecular links between
      EGFR and VEGFR2 inhibition. CONCLUSIONS: Results show antitumor synergy for
      combined EGFR and VEGFR2 targeted therapy, supporting the significant therapeutic
      potential of this combination strategy.

PMID- 16609037
TI  - Antisense suppression of pygopus2 results in growth arrest of epithelial ovarian
      cancer.
AB  - PURPOSE: The Pygopus proteins are critical elements of the canonical Wnt/beta
      catenin transcriptional complex. In epithelial ovarian cancer, constitutively
      active Wnt signaling is restricted to one (endometrioid) tumor subtype. The
      purpose of this study was to determine the level of expression and growth
      requirements of human Pygopus2 (hPygo2) protein in epithelial ovarian cancer.
      EXPERIMENTAL DESIGN: Expression and subcellular localization of hPygo2 was
      determined in epithelial ovarian cancer cell lines and tumors using Northern
      blot, immunoblot, and immunofluorescence. Immunohistochemistry was done on 125
      archived patient epithelial ovarian cancer tumors representing all epithelial
      ovarian cancer subtypes. T-cell factor-dependent transcription levels were
      determined in epithelial ovarian cancer cells using TOPflash/FOPflash in vivo
      assays. Phosphorothioated antisense oligonucleotides were transfected into cell
      lines and growth assayed by cell counting, anchorage-independent colony formation
      on soft agar, and xenografting into severe combined immunodeficient mice.
      RESULTS: All six epithelial ovarian cancer cell lines and 82% of the patient
      samples overexpressed nuclear hPygo2 compared with control cells and benign
      disease. Depletion of hPygo2 by antisense oligonucleotides in both Wnt-active
      (TOV-112D) and Wnt-inactive serous (OVCAR-3, SKOV-3) and clear cell (TOV-21G)
      carcinoma cell lines halted growth, assessed using tissue culture, anchorage
      independent, and xenograft assays. CONCLUSIONS: hPygo2 is unexpectedly widely
      expressed in, and required in the absence of, Wnt signaling for malignant growth
      of epithelial ovarian cancer, the deadliest gynecologic malignancy. These
      findings strongly suggest that inhibition of hPygo2 may be of therapeutic benefit
      for treating this disease.

PMID- 16609036
TI  - Allogeneic MHC gene transfer enhances antitumor activity of allogeneic
      hematopoietic stem cell transplantation without exacerbating graft-versus-host
      disease.
AB  - Enhancement of the specific antitumor activity of allogeneic hematopoietic stem
      cell transplantation (alloHSCT) against solid cancers is a major issue in the
      clinical oncology. In this study, we examined whether intratumoral allogeneic MHC
      (alloMHC) gene transfer can enhance the recognition of tumor-associated antigens
      by donor T cells and augment the antitumor activity of alloHSCT. In minor
      histocompatibility antigen-mismatched alloHSCT (DBA/2-->BALB/c: H-2(d))
      recipients, alloMHC gene (H-2K(b)) was transduced directly into a s.c. tumor of
      CT26 colon cancer cells. Because CT26 cells have an aggressive tumorigenicity in
      syngeneic BALB/c mice, an H-2K(b) gene transfer provides only a limited antitumor
      effect after syngeneic (BALB/c-->BALB/c) HSCT. By contrast, the H-2K(b) gene
      transfer caused significant tumor suppression in the alloHSCT recipients, and
      this suppression was evident not only in the gene-transduced tumors but also in
      simultaneously inoculated distant tumors without gene transduction. In vitro
      cytotoxicity assay showed specific tumor cell lysis by donor T cells responding
      to the H-2K(b) gene transfer. Graft-versus-host disease was not exacerbated
      serologically or clinically in the treated mice, demonstrating that alloMHC gene
      transfer enhances the antitumor effects of alloHSCT without exacerbating graft
      versus-host disease. This combination strategy has important implications for the
      development of therapies for human solid cancers.

PMID- 16609038
TI  - Targeting gastrin-releasing peptide receptors on small cell lung cancer cells
      with a bispecific molecule that activates polyclonal T lymphocytes.
AB  - PURPOSE: Gastrin-releasing peptide (GRP) is a growth factor for small cell lung
      cancer (SCLC). GRP belongs to the bombesin peptide family and has significant
      homology to bombesin. We constructed a bispecific molecule, OKT3xAntag2, by
      conjugating a monoclonal antibody OKT3 (anti-CD3) with a bombesin/GRP antagonist
      (Antag2) and evaluated cytotoxicity against SCLC cells. EXPERIMENTAL DESIGN: We
      tested binding of the bispecific molecule to SCLC cell lines and T cells by flow
      cytometry, antibody-dependent cellular cytotoxicity (ADCC) of SCLC cells in vitro
      and in a murine SCLC xenograft model. We studied SCLC apoptosis and necrosis
      during ADCC and the activity and cleavage of caspase-3, caspase-9, and poly(ADP
      ribose) polymerase (PARP). RESULTS: The bispecific molecule functions as a cross
      linker between T cells and SCLC cells, induces T cell activation, and mediates
      ADCC of SCLC cells; 40% to 80% growth inhibition of SCLC cells mediated by the
      bispecific molecule at low effector to target cell ratios was achieved.
      Activation of T cells by the bispecific molecule resulted in significant
      increases in IFNgamma production and apoptosis and necrosis of SCLC cells
      associated with cleavage of PARP and caspase-3. Targeted immunotherapy with the
      bispecific molecule-armed human T cells significantly reduced SCLC tumor burdens
      in a mouse model. CONCLUSION: The bispecific molecule OKT3xAntag2 mediates growth
      inhibition and apoptosis of SCLC cells by activated T cells through activation
      and cleavage of caspase-3 and PARP in vitro and in vivo. Clinical trials of this
      bispecific molecule through adoptive transfer of ex vivo activated T cells in GRP
      receptor-positive tumors, such as SCLC, are warranted.

PMID- 16609039
TI  - Erythropoietin fails to interfere with the antiproliferative and cytotoxic
      effects of antitumor drugs.
AB  - PURPOSE: Erythropoietin (EPO) therapy is widely used for the prevention and
      treatment of anemia resulting from cancer chemotherapy. Native EPO regulates
      erythropoiesis, at least in part, by protecting erythroid progenitor cells from
      apoptotic cell death. The recent discovery of the EPO receptor (EPOR) on cancer
      cells raises the concern that EPO therapy might stimulate tumor growth and/or
      protect cancer cells from drug-induced apoptosis. Therefore, the capacity of EPO
      to interfere with the effects of conventional chemotherapeutic drugs on
      proliferation, apoptosis, and the induction of senescence was investigated in MCF
      7 and MDA-MB231 breast tumor cells, which express the EPOR as well as in F-MEL
      erythroleukemia cells. EXPERIMENTAL DESIGN: Breast cancer cells and F-MEL
      leukemic cells were cultured in the presence or absence of EPO and then exposed
      to antitumor drugs. Cell proliferation was assessed by a standard 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction assay 72
      hours after drug exposure. Cytotoxicity was monitored by clonogenic survival.
      Apoptosis was evaluated either by the terminal deoxyribonucleotide transferase
      mediated nick-end labeling assay or fluorescence-activated cell sorting analysis,
      and senescence was monitored by beta-galactosidase staining. EPO signaling was
      assessed by monitoring the phosphorylation/activation of specific signaling
      proteins. RESULTS: EPO failed to stimulate the proliferation of MCF-7 or MDA
      MB231 breast tumor cells or F-MEL leukemic cells. EPO treatment also failed to
      interfere with the antiproliferative and/or cytotoxic effects of Adriamycin,
      Taxol, and tamoxifen in breast tumor cells (or of cytarabine and daunorubicin in
      F-MEL cells). EPO failed to prevent apoptosis induced by Taxol or senescence
      induced by Adriamycin in MCF-7 cells. EPO stimulated the activation of
      extracellular signal-regulated kinase, p38, and c-Jun-NH(2)-kinase in MCF-7 cells
      but did not activate Akt or signal transducers and activators of transcription 5
      (STAT5). EPO failed to activate any of these signaling pathways in MDA-MB231
      cells. Cytarabine and daunorubicin interfered with EPO signaling in F-MEL cells.
      CONCLUSIONS: These findings suggest that EPO is unlikely to directly counteract
      the effectiveness of cancer chemotherapeutic drugs. This may be a consequence of
      either ineffective signaling through the EPOR or drug-mediated suppression of EPO
      signaling.

PMID- 16609040
TI  - Synergistic interactions between DMAG and mitogen-activated protein kinase kinase
      1/2 inhibitors in Bcr/abl+ leukemia cells sensitive and resistant to imatinib
      mesylate.
AB  - PURPOSE: To characterize interactions between the heat shock protein 90
      antagonist 17-dimethylaminoethylamino-17-demethoxygeldanamycin (DMAG) and the
      mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK)
      kinase 1/2 inhibitor PD184352 in Bcr/abl(+) leukemia cells sensitive and
      resistant to imatinib mesylate. EXPERIMENTAL DESIGN: K562 and LAMA 84 cells were
      exposed to varying concentrations of DMAG and PD184352 for 48 hours; after which,
      mitochondrial integrity, caspase activation, and apoptosis were monitored.
      Parallel studies were done in imatinib mesylate-resistant cells, including BaF3
      cells transfected with plasmids encoding clinically relevant Bcr/abl mutations
      conferring imatinib mesylate resistance (e.g., E255K, M351T, and T315I) and
      primary CD34(+) bone marrow cells from patients refractory to imatinib mesylate.
      RESULTS: Cotreatment of Bcr/abl(+) cells with minimally toxic concentrations of
      DMAG and PD184352 resulted in synergistic induction of mitochondrial injury
      (cytochrome c release and Bax conformational change), events associated with the
      pronounced and sustained inactivation of ERK1/2 accompanied by down-regulation of
      Bcl-x(L). Conversely, cells ectopically expressing Bcl-x(L) displayed significant
      protection against PD184352/DMAG-mediated lethality. This regimen effectively
      induced apoptosis in K562 cells overexpressing Bcr/abl, in BaF3 cells expressing
      various clinically relevant Bcr/abl mutations, and in primary CD34(+) cells from
      patients resistant to imatinib mesylate, but was relatively sparing of normal
      CD34(+) bone marrow cells. CONCLUSIONS: A regimen combining the heat shock
      protein 90 antagonist DMAG and the mitogen-activated protein kinase/ERK kinase
      1/2 inhibitor potently induces apoptosis in Bcr/abl(+) cells, including those
      resistant to imatinib mesylate through various mechanisms including Bcr/abl
      kinase mutations, through a process that may involve sustained ERK1/2
      inactivation and Bcl-x(L) down-regulation. This strategy warrants further
      attention in Bcr/abl(+) hematopoietic malignancies, particularly those resistant
      to Bcr/abl kinase inhibitors.

PMID- 16609041
TI  - Preclinical efficacy and pharmacokinetics of AP5346, a novel diaminocyclohexane
      platinum tumor-targeting drug delivery system.
AB  - PURPOSE: AP5346 is designed to target a diaminocyclohexane platinum (Pt) moiety
      to tumors through pH-sensitive linkage to a 25 kDa hydroxypropylmethacrylamide
      polymer. The goal of these studies was to determine the rate of release of Pt as
      a function of pH, the antitumor activity, and plasma and tumor pharmacokinetics
      of AP5346 in preclinical models. EXPERIMENTAL DESIGN: Antitumor activity was
      assessed in mice bearing B16F10 melanoma and M5076 and 2008 ovarian carcinomas.
      Pt levels in plasma, tumors, and tumor DNA were measured by atomic absorption and
      inductively coupled plasma mass spectrometry. RESULTS: AP5346 did not release Pt
      when suspended in 5% dextrose and released only 3.5% of its Pt in 24 hours in
      buffer at pH 7.4; the rate of release was 7-fold higher at pH 5.4. When given at
      their respective maximum tolerated doses, the antitumor activity of AP5346 was
      superior to that of oxaliplatin against both the B16 melanoma and 2008 human
      ovarian carcinoma. It was more effective than cisplatin in both cisplatin
      sensitive and cisplatin-resistant variants of the M5076 tumor. When given at
      equitoxic doses, the peak plasma concentration was 25-fold higher, and AUC((0
      infinity)) was 93 times higher, for AP5346 than for oxaliplatin. AP5346 delivered
      16.3-fold more Pt to the tumor and 14.2-fold more Pt to tumor DNA than
      oxaliplatin based on AUC((1-168)). CONCLUSIONS: AP5346 has a substantially better
      therapeutic index than oxaliplatin. AP5346 produced a marked increase in the
      delivery of diaminocyclohexane Pt to the tumor and tumor DNA over and above that
      attainable with oxaliplatin.

PMID- 16609042
TI  - Development and therapeutic options for the treatment of raloxifene-stimulated
      breast cancer in athymic mice.
AB  - PURPOSE: Selective estrogen receptor modulators (SERM) are used for the treatment
      and prevention of breast cancer (tamoxifen) and osteoporosis (raloxifene).
      Mechanisms of tamoxifen-resistance in breast cancer are incompletely understood
      but current research is focused on crosstalk between growth factor receptors and
      the estrogen receptor alpha (ERalpha) pathway. There is increasing clinical use
      of raloxifene for the treatment of osteoporosis, but the widespread use of this
      SERM will have consequences for the treatment of breast cancer in raloxifene
      exposed women. EXPERIMENTAL DESIGN: We took the strategic step of developing a
      raloxifene-resistant tumor (MCF-7RALT) model in vivo and investigating the
      mechanisms responsible for resistance. RESULTS: MCF-7RALT tumors exhibited phase
      I SERM resistance, growing in response to SERMs and 17beta-estradiol. Epidermal
      growth factor receptor/HER1 and HER2/neu mRNAs were increased in MCF-7RALT
      tumors. The HER2/neu blocker, trastuzumab, but not the epidermal growth factor
      receptor blocker, gefitinib, decreased the growth of MCF-7RALT tumors in vivo.
      Consequently, trastuzumab decreased prosurvival/proliferative proteins: phospho
      HER2/neu, total HER2/neu, phospho-Akt (protein kinase B), glycogen synthetase
      kinase-3, cyclin D1, and the antiapoptotic protein X chromosome-linked inhibitor
      of apoptosis, whereas increasing the proapoptotic protein, caspase-7, in
      raloxifene-treated MCF-7RALT tumors. Interestingly, ERalpha protein was
      overexpressed in untreated MCF-7RALT tumors and hyperactivated in cells derived
      from these tumors. Only fulvestrant completely inhibited the growth and ERalpha
      activity of MCF-7RALT tumors. The coactivator of ERalpha, amplified in breast
      cancer-1 protein was modestly increased in the raloxifene-treated MCF-7RALT
      tumors and increased both basal and estradiol-induced activity of ERalpha in
      cells derived from the MCF-7RALT tumors. CONCLUSIONS: These results suggest that
      overexpression and increased activity of HER2/neu might be responsible for the
      development of raloxifene-resistant breast cancer. The results also suggest that
      increased expression of basal activity of ERalpha could contribute to the
      hypersensitivity of MCF-7RALT tumors in response to estradiol because only
      fulvestrant blocked growth and ERalpha activity.

PMID- 16609043
TI  - Use of an orthotopic xenograft model for assessing the effect of epidermal growth
      factor receptor amplification on glioblastoma radiation response.
AB  - PURPOSE: The influence of epidermal growth factor receptor (EGFR) amplification
      on glioblastoma patient prognosis following definitive radiotherapy has been
      extensively investigated in clinical studies, and yet the relationship between
      EGFR status and radiation response remains unclear. The intent of the current
      study was to address this relationship using several EGFR-amplified glioblastoma
      xenografts in an orthotopic athymic mouse model. EXPERIMENTAL DESIGN: We examined
      the effect of radiation on the survival of nude mice with intracranial xenografts
      derived from 13 distinct patient tumors, 7 of which have amplified EGFR. Mice
      with established intracranial tumors were randomized to sham treatment or 12-Gy
      radiation in six fractions delivered over 12 days. RESULTS: For six of the
      xenografts, radiation of mice with intracranial tumor significantly extended
      survival, and four of these xenografts had EGFR amplification. For seven other
      xenografts, radiation treatment did not significantly extend survival, and three
      of these, including GBM12, had EGFR amplification. Similar to EGFR, the tumor
      genetic status of p53 or PTEN did not show preferential association with
      radiation-sensitive or radiation-resistant xenografts whereas
      hyperphosphorylation of Akt on Ser(473) was associated with increased
      radioresistance. To specifically investigate whether inhibition of EGFR kinase
      activity influences radiation response, we examined combined radiation and EGFR
      inhibitor treatment in mice with intracranial GBM12. The combination of oral
      erlotinib administered concurrently with radiation resulted only in additive
      survival benefit relative to either agent alone. CONCLUSIONS: Our results
      indicate that EGFR amplification, as a biomarker, is not singularly predictive of
      glioblastoma response to radiation therapy, nor does the inhibition of EGFR
      enhance the intrinsic radiation responsiveness of glioblastoma tumors. However,
      efficacious EGFR inhibitor and radiation monotherapy regimens can be used in
      combination to achieve additive antitumor effect against a subset of
      glioblastoma.

PMID- 16609044
TI  - Prevention of ultraviolet radiation-induced immunosuppression by (-)
      epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent
      DNA repair.
AB  - PURPOSE: Solar UV radiation-induced immunosuppression is considered to be a risk
      factor for melanoma and nonmelanoma skin cancers. We previously have shown that
      topical application of (-)-epigallocatechin-3-gallate (EGCG) prevents UV-induced
      immunosuppression in mice. We studied whether prevention of UV-induced
      immunosuppression by EGCG is mediated through interleukin 12 (IL-12)-dependent
      DNA repair. EXPERIMENTAL DESIGN: IL-12 knockout (KO) mice on C3H/HeN background
      and DNA repair-deficient cells from xeroderma pigmentosum complementation group A
      (XPA) patients were used in this study. The effect of EGCG was determined on UV
      induced suppression of contact hypersensitivity and UV-induced DNA damage in the
      form of cyclobutane pyrimidine dimers (CPD) in mice and XPA-deficient cells using
      immunohistochemistry and dot-blot analysis. RESULTS: Topical treatment with EGCG
      prevented UV-induced suppression of the contact hypersensitivity in wild-type
      (WT) mice but did not prevent it in IL-12 KO mice. Injection of anti-IL-12
      monoclonal antibody to WT mice blocked the preventive effect of EGCG on UV
      induced immunosuppression. EGCG reduced or repaired UV-induced DNA damage in skin
      faster in WT mice as shown by reduced number of CPDs(+) cells and reduced the
      migration of CPD(+) antigen-presenting cells from the skin to draining lymph
      nodes. In contrast, this effect of EGCG was not seen in IL-12 KO mice. Further,
      EGCG was able to repair UV-induced CPDs in XPA-proficient cells obtained from
      healthy person but did not repair in XPA-deficient cells, indicating that
      nucleotide excision repair mechanism is involved in DNA repair. CONCLUSIONS:
      These data identify a new mechanism by which EGCG prevents UV-induced
      immunosuppression, and this may contribute to the chemopreventive activity of
      EGCG in prevention of photocarcinogenesis.

PMID- 16609045
TI  - Analysis of c-ErbB1/epidermal growth factor receptor and c-ErbB2/HER-2 expression
      in bronchial dysplasia: evaluation of potential targets for chemoprevention of
      lung cancer.
AB  - PURPOSE: Lung cancer is preceded by a premalignant phase during which
      intervention could decrease associated morbidity and mortality. Molecular
      characterization of factors involved in controlling progression of bronchial
      dysplasias will provide markers of premalignant change and identify targets for
      chemoprevention. EXPERIMENTAL DESIGN: Immunohistochemical analysis of epidermal
      growth factor receptor (EGFR; c-ErbB1/EGFR), HER-2/neu (c-ErbB2/HER-2), Ki-67,
      and minichromosome maintenance protein 2 (MCM2) expression in bronchial dysplasia
      was undertaken to characterize molecular alterations associated with the
      progression of these lesions in 268 bronchoscopically obtained biopsies from 134
      subjects. RESULTS: Analysis of biopsies with the most severe diagnosis from each
      subject showed a linear relationship between increasing marker expression and
      severity of dysplastic change for EGFR (P < 0.001), Ki-67 (P < 0.001), and MCM2
      (P = 0.001) but not HER-2 (P = 0.102). Increased expression of either EGFR or HER
      2 was associated with increased levels of Ki-67 and MCM2 expression, and combined
      overexpression of these receptors was associated with the highest levels of
      proliferation, suggesting a synergistic effect. Finally, the lack of an
      associated trend toward increased EGFR expression when comparing the worst and
      best biopsies within each subject indicated a potential field effect in the
      induction of EGFR expression. CONCLUSIONS: The results suggest a prominent role
      for EGFR overexpression in the development and progression of bronchial dysplasia
      and provide rationale for exploring inhibition of EGFR signaling in lung cancer
      chemoprevention.

PMID- 16609046
TI  - Interaction between p53 staining and high-dose chemotherapy in breast cancer.

PMID- 16609047
TI  - Innovations and challenges in melanoma: summary statement from the first
      Cambridge conference.
AB  - Innovations and Challenges in Melanoma, chaired by Michael Atkins and cochaired
      by Ulrich Keilholz, John Kirkwood, and Jeffrey Sosman, was held July 15 to 16,
      2005, in Cambridge, Massachusetts. The conference brought together leading
      experts in the fields of cancer research, medical oncology, surgical oncology,
      anatomic pathology, dermatology, and immunotherapy who wished to advance the
      field of melanoma treatment by exchanging information and perspectives regarding
      recent advances and recommendations for further study. The conference proceedings
      published in this educational supplement to Clinical Cancer Research are intended
      to provide timely information and recommendations on how genetics, biology, and
      data information can enhance our understanding of melanoma biology and help
      inform the use of therapies for this disease.

PMID- 16609048
TI  - Progress and prospects on melanoma: the way forward for early detection and
      reduced mortality.
AB  - The public health problem of melanoma is difficult. Recent decades have seen
      substantial efforts directed at primary prevention, yet the incidence of melanoma
      continues to increase. Substantial efforts have been devoted to improving
      treatment, yet melanoma retains a poor prognosis if simple surgical excision is
      not curative. Early detection has made remarkable progress, however. Five-year
      relative survival has increased from approximately 80% in 1975 to greater than
      90% in 1996. Even so, almost 8,000 Americans are projected to succumb to melanoma
      in 2005. Because most of these fatal melanomas are visible on the skin surface at
      a curable phase in their evolution, more can and must be done. To improve the
      early detection practices of clinicians, we have developed an eight-step Basic
      Skin Cancer Triage algorithm, which forms the core of a curriculum that we have
      shown can result in improved skills, attitudes, and practices. We are now in the
      process of attempting to test a Web-based version of that curriculum in a
      randomized trial. Skin self-examination also has tremendous potential for
      contributing to early detection of melanoma. We have tested an intervention to
      encourage thorough skin self-examination in a randomized trial and found it
      effective in increasing the performance of this procedure, on increase that is
      sustained for at least a year, while resulting in only short-term increases in
      surgical procedures on the skin. Early detection has not yet reached its full
      potential effect on the public health problem of melanoma and is poised to
      further reduce melanoma mortality.

PMID- 16609049
TI  - Genetic alterations in signaling pathways in melanoma.
AB  - Alterations in the RAS signaling cascade are almost uniformly present in
      melanoma. RAS itself is only infrequently mutated in melanoma although downstream
      of RAS lie BRAF on the mitogen-activated protein kinase pathway and PTEN on the
      protein kinase B/Akt pathway. These genes are often altered in melanomas; indeed,
      the most frequent target of mutation in melanomas is BRAF, which is mutated in
      approximately 60% to 70% of superficial spreading melanomas. These mutations
      occur in a background that is not normal, with the CDKN2A locus also typically
      being mutated. We review herein the data that suggest that the distribution of
      the signaling mutations is important. In general, melanomas carry a mutated NRAS,
      a mutated BRAF, or concurrent BRAF and PTEN mutations. These data support the
      hypothesis that the biochemical functions of RAS are portioned by mutations in
      the pathways lying downstream. Moreover, these mutations have no apparent
      relationship to the patterns of alteration of CDKN2A and its downstream
      effectors. Thus, the data also suggest that successful exploitation of mutations
      in melanoma will be dependent on understanding not only mutations and their
      frequency but their genetic context as well.

PMID- 16609050
TI  - Pathology of melanoma.
AB  - The purposes of pathologic examination of a lesion suspected of being a malignant
      melanoma are to provide an accurate diagnosis of melanoma (or not), and to
      provide prognostic information useful in the clinical management of the patient.
      In the near future, pathologic attributes will also likely be used to predict
      responses to therapy, as a guide to the selection of specific therapeutic agents
      such as "small molecule" inhibitors of signaling pathways.

PMID- 16609051
TI  - Early-stage melanoma: staging criteria and prognostic modeling.
AB  - Accurate risk assessment is central to the process of making rational surgical
      and systemic treatment recommendations for melanoma patients and in establishing
      appropriate clinical trial stratification criteria. The current American Joint
      Commission on Cancer melanoma staging system incorporated relevant prognostic
      variables to provide a framework for the estimation of risk for recurrence;
      however, significant prognostic heterogeneity exists within the stage groupings.
      In the stage I/II group, survival rates range from 40% to 95% as defined by the
      combination of tumor thickness and ulceration. The use of novel prognostic
      factors, such as mitotic rate, sentinel node biopsy, and prognostic modeling
      using a variety of factors, can minimize this prognostic heterogeneity and
      provide a more accurate and individualized prognostic profile. Recent
      modifications in the stage III criteria include the number of positive nodes,
      whether the nodal disease is microscopic or clinically apparent, and the presence
      of an ulcerated primary. Through these factors, survival estimates can be
      provided, but like the stage I/II group, wide ranges in prognosis exist. The
      complexion of the stage III population is in evolution as a result of increasing
      numbers of patients being diagnosed as having microscopic sentinel node disease.
      Contemporary efforts are focused on defining the prognosis and natural history of
      this group. Through prognostic modeling using the number of nodes involved,
      ulceration status, and a measure of disease burden--disease in the sentinel node-
      relatively homogeneous subgroups can be identified. Long-term follow-up of
      patients staged with PCR molecular techniques on sentinel nodes shows conflicting
      value in assessing prognosis and therefore cannot be routinely used outside a
      clinical trial. The combination of genomic profiling using microarray analyses
      and the development of targeted therapy holds the future promise of
      individualizing prognosis and therapy.

PMID- 16609052
TI  - Sentinel lymph node biopsy and melanoma biology.
AB  - Minimally invasive intraoperative lymphatic mapping and sentinel node biopsy has
      become the standard approach for staging the regional lymph nodes for early-stage
      melanoma. The procedure requires close collaboration of surgeon, pathologist, and
      nuclear medicine physician. The strength of lymphatic mapping and sentinel node
      biopsy is its accuracy of detecting occult lymph node metastases. Reverse
      transcriptase-PCR (RT-PCR) analyses of either fresh-frozen or paraffin-embedded
      sections of the sentinel lymph nodes have been found to be more sensitive than
      H&E staining or immunohistochemistry techniques, but lack of specificity and
      limits in the availability of tissue specimens make this technique impractical
      for routine use. Three randomized clinical trials are examining the therapeutic
      value of lymphatic mapping and sentinel node biopsy for melanoma. Preliminary
      results of the Multicenter Lymphadenectomy Trial I show the high level of
      accuracy and low morbidity of lymphatic mapping and sentinel node biopsy done
      through an international working group. The therapeutic value of lymphatic
      mapping and sentinel node biopsy is still unclear. Multicenter Lymphadenectomy
      Trial II will test the clinical significance of lymph nodes evaluated by RT-PCR
      and the value of completion lymph node dissection for patients found to have
      tumor-positive sentinel lymph nodes by H&E, immunohistochemistry, or RT-PCR. The
      Sunbelt Melanoma Trial examines the therapeutic value of completion dissection
      and benefits of Intron A. The ability to detect occult nodal metastases and
      evaluate the interaction of primary tumor with the regional lymph nodes may
      provide for better understanding of the metastatic process in patients with
      melanoma and help to determine the function of the regional lymph nodes as
      markers of metastases or incubators of tumor cells in the metastatic cascade.

PMID- 16609053
TI  - Identifying and overcoming immune resistance mechanisms in the melanoma tumor
      microenvironment.
AB  - The continually growing list of defined tumor antigens is broadening the
      potential applicability of tumor antigen-targeted cancer therapies. Although
      cancer vaccines and adoptive T-cell transfer have been shown to increase the
      frequency of circulating tumor antigen-specific T cells, these approaches cause
      clinical responses in a few patients. In melanoma, approximately one third of
      metastatic lesions contain activated T cells, including those specific for tumor
      antigens, arguing that the priming phase has occurred already in such individuals
      even without vaccination. These observations indicate that tumor resistance to
      immune destruction may dominate in many instances, arguing for a thorough
      analysis of the melanoma tumor microenvironment in individual patients. Recent
      work has suggested that T-cell anergy, the influence of CD4+ CD25+ regulatory T
      cells, the expression of inhibitory ligands, such as PD-L1, and the activity of
      nutrient-catabolizing enzymes, such as indoleamine 2,3-dioxygenase, may be
      involved. Preclinical murine models have shown that interfering with each of
      these processes can translate into T-cell-mediated tumor control. Importantly,
      each of these targets is amenable to clinical manipulation. Clinical translation
      of these approaches to counter negative regulation of antitumor immunity should
      receive high priority.

PMID- 16609054
TI  - Strategies for the development of more effective adjuvant therapy of melanoma:
      current and future explorations of antibodies, cytokines, vaccines, and
      combinations.
AB  - Adjuvant trials have evaluated the influence of multiple agents on relapse and
      mortality for patients with intermediate-risk (stage IIA, American Joint
      Committee on Cancer staging manual, 6th ed.), high-risk (stage IIB-III), or very
      high-risk (stage IIIB-IV) operable melanoma. A 25% to 33% reduction of relative
      relapse risk with high-dose IFN-alpha2b therapy has been documented in stage
      groups overall, with survival prolongation in two of these trials. In contrast,
      no large cooperative group trial has ever shown a significant prolongation of
      survival for inoperable advanced stage IV melanoma. The basis for the failure of
      therapies in advanced disease may lie in differences in the immune function of
      patients with active metastatic stage IV disease. These observations argue for
      the exploration of promising new therapies in adjuvant settings. Past adjuvant
      studies have targeted stage IIB-III patients, focusing less on the more advanced
      but resectable stage IIIB and IV (M(1a-b)) disease groups. Current
      chemobiotherapy (S0008) and granulocyte-macrophage colony-stimulating factor plus
      peptide vaccination (E4697) trials have now evaluated the higher-risk disease
      groups where trials may soon be expected to yield results. Predictive markers
      that would allow us to focus treatment on those patients who are most likely to
      respond would accelerate our development of adjuvant therapy for melanoma. We
      have recently developed a neoadjuvant approach to high-dose IFN in which the
      molecular and immunologic effects of IFN have been correlated with clinical
      antitumor effects of this therapy. In addition, the Hellenic Oncology group has
      shown that the benefit of high-dose IFN is closely correlated with serologic and
      clinical manifestations of autoimmunity. These new insights will allow us to
      develop more efficient approaches to adjuvant therapy of melanoma, focusing on
      autoimmunity and antitumor immunity with new immunomodulators, such as anti-CTLA4
      antibodies and vaccination.

PMID- 16609055
TI  - Allogeneic and autologous melanoma vaccines: where have we been and where are we
      going?
AB  - The past three decades have seen substantial research on vaccines for the
      treatment of metastatic melanoma and the prevention of recurrence following
      resection. Despite their enormous promise, the actual results have been
      disappointing, with several high-profile vaccine clinical trials failing to show
      a benefit. Nonetheless, enthusiasm for melanoma vaccines remains and has
      increased with our expanding understanding of the immune response to tumor.
      Cellular vaccines can be divided into autologous, derived from the patient's own
      tumor and allogeneic vaccines. Autologous vaccines have the advantage of
      containing all potentially relevant tumor-associated antigens for that particular
      patient. However, autologous vaccines are difficult to obtain from most patients
      with advanced disease and impossible to obtain from patients who present after
      resection of all clinically evident disease. No consensus exists for how tumors
      should be processed, preserved, modified, and delivered to serve as an effective
      vaccine. The amount of autologous tumor available is rarely enough to produce
      more than two or three vaccination doses, and the time between initial tumor
      harvest and ultimate availability of the vaccine may result in interval tumor
      progression that diminishes the likelihood of vaccine efficacy. All these
      drawbacks of autologous tumor vaccination limit its applicability and also limit
      the ability to test autologous vaccines in prospective trials. Allogeneic
      vaccines avoid many of these problems, but may not contain all of the tumor
      associated antigens present on the patient's own tumor. In particular,
      neoantigens created by mutations in the patient's tumor would be unlikely to be
      represented in an allogeneic vaccine. Although allogeneic vaccines can be
      manufactured in sufficient quantities to allow large-scale trials, there remain
      significant limiting issues in the manufacture and standardization of the vaccine
      product.

PMID- 16609056
TI  - Peptide and dendritic cell vaccines.
AB  - There has been a rush to convert discovery of new melanoma antigens into cancer
      vaccines for the therapy of melanoma. The result has been disappointing from a
      clinical standpoint. The premise behind rapid pursuit of peptide vaccines for
      melanoma therapy was that the spontaneous tumor-associated immune response was
      too weak to be effective. However, it is increasingly clear that the host-tumor
      relationship is a complex interplay of immune response, immune escape, and immune
      adaptation, with multiple layers of regulatory control and modulation of
      responses over time. The lesion in the immune response to cancer is much more
      complex than simply a weak immune response to defined antigens. Current results
      should serve as a call to take a closer look at immune regulatory processes and
      principles and to develop more comprehensive and multiagent approaches to
      modulate the host-tumor relationship. Development of effective immune therapy for
      cancer will require (a) more comprehensive and real-time immune monitoring in
      various tissue compartments and (b) patient-specific modulation of immune
      responses, informed by the real-time monitoring. Peptide antigens associated with
      MHC class I or class II molecules are the molecular targets for T-cell
      recognition of cancer. To characterize the host-tumor relationship and to
      optimize cancer vaccines, clinical studies using defined peptide antigens offer
      special opportunities to advance the field and thus have an important place in
      the ongoing development of effective immune therapy of melanoma.

PMID- 16609057
TI  - Immune monitoring of T-cell responses in cancer vaccine development.
AB  - Monitoring cellular immune responses is one prerequisite for rational development
      of cancer vaccines. The primary objective of immune monitoring is to determine
      the efficacy of a vaccine to induce or augment a specific T-cell response.
      Further questions relate to the prevalence and functional relevance of
      spontaneous tumor-directed immune responses, the functional characteristics of T
      cell responses, and, finally and most importantly, the relationship between
      immune monitoring assay results and clinical end points. The issue of T-cell
      monitoring has become more complex as different types and generations of assays
      have been adopted during the past decade and both standardization and validation
      of assays have often been insufficient. Because the development of assays
      parallel the clinical development of cancer vaccines, technical advances have
      been achieved simultaneously with broadening understanding of cancer immunity.
      Suitable animal models for immune monitoring are, however, lacking, because
      preclinical vaccine development in rodents does not allow serial immune
      monitoring of the peripheral blood, as is commonly used in patients. The current
      situation is characterized by a lack of universal standards for T-cell
      assessment, uncertainty about the association between immune monitoring assay
      results and clinical antitumor end points, and lack of knowledge regarding the
      contribution of different aspects of T-cell function to clinical efficacy. It is
      acknowledged that T-cell monitoring will have to be validated in large trials
      with clinically effective vaccines, but this necessity should not discourage the
      current application of novel assays within clinical trials of all stages.

PMID- 16609058
TI  - Cytokine-based therapy and biochemotherapy for advanced melanoma.
AB  - A variety of immunotherapeutic approaches have shown activity in patients with
      metastatic melanoma with the best results being observed with interleukin 2 (IL
      2). Follow-up data through 2004 confirm the durability of responses produced by
      the Food and Drug Administration-approved high-dose IL-2 regimen in this patient
      population. Efforts to develop more tolerable and/or effective IL-2-based
      treatment regimens by either prolonged administration of lower doses or the
      combination of IL-2 with other cytokines, monoclonal antibodies, or vaccines have
      yet to produce results superior to those seen with high-dose IL-2 alone. Recent
      investigations have suggested that, in some patients, IL-2 may expand regulatory
      T-cell populations leading to immune tolerance rather than antitumor immunity.
      Efforts to shift this balance in favor of immune rejection by reducing the
      confounding effects of regulatory T cells on IL-2 therapy or the use of novel and
      potentially more purely immunostimulatory cytokines are ongoing. Despite
      promising phase 2 data, phase 3 studies have failed to show meaningful clinical
      benefit for the combination of cytokines with cytotoxic chemotherapy, so-called
      "biochemotherapy." Nonetheless, recent investigations with biochemotherapy
      followed by maintenance immunotherapy suggest that biochemotherapy may still have
      a role as a "bridge to immunotherapy" in some patients with rapidly progressive
      disease. Given the low number of patients achieving durable benefit with cytokine
      based immunotherapy, considerable recent effort has focused on identifying
      predictors of therapeutic response. Investigations suggest that immune
      responsiveness may be predetermined by a tumor microenvironment conducive to
      immune recognition and the host propensity to develop autoimmunity. Efforts to
      understand and further define pretreatment predictors of response through the use
      of gene expression and proteomic techniques are ongoing and raise the potential
      for eventually limiting cytokine-based immunotherapy to those most likely to
      benefit.

PMID- 16609059
TI  - Immunosuppression in melanoma immunotherapy: potential opportunities for
      intervention.
AB  - Although melanomas are substantially more immunogenic than other tumors, current
      immunotherapeutic approaches for melanoma patients have met with only limited
      success. Although melanoma-specific CD8+ T-cell responses can often be generated
      in patients naturally or through vaccination regimens, tumors frequently continue
      to grow unabated, suggesting that tumor-specific immune responses may be actively
      dampened in vivo. Research over the past decade has brought to light several
      mechanisms used by melanomas and other tumors to suppress tumor-specific immune
      responses. These include the presence of regulatory immune cells within the tumor
      microenvironment and draining lymph nodes that serve to shut down effector T-cell
      function. In addition, melanoma tumors themselves express a number of soluble and
      membrane-bound molecules that are responsible for inhibiting activated immune
      cells. The identification of these suppressive mechanisms has provided
      significant opportunities for designing novel therapeutic interventions that
      could augment current vaccination and adoptive transfer approaches for treatment
      of melanoma.

PMID- 16609060
TI  - Chemotherapy and targeted therapy combinations in advanced melanoma.
AB  - For three decades, clinical trials with chemotherapy in melanoma have failed to
      show superiority of any one regimen over another. Dacarbazine remains the only
      "standard" agent. With response rates of <10% and median progression-free
      survival of 2 months or less in contemporary trials, there is a need to improve
      systemic therapy. Combination chemotherapy is associated with higher response
      rates than single-agent therapy but this has not translated into improved
      survival. An increasing number of potential therapeutic targets have been
      identified. For some, pharmacologic inhibitors are available, including sorafenib
      for BRAF, farnesyltransferase inhibitors for NRAS, PD-0325901 for mitogen
      activated protein kinase/extracellular signal-regulated kinase kinase, rapamycin
      analogues for mammalian target of rapamycin, and agents that inhibit either
      vascular endothelial growth factor or its receptors. Several multitargeted kinase
      inhibitors have potency against the fibroblast growth factor receptor, c-kit, and
      platelet-derived growth factor receptor. Small-molecule inhibitors of c-met and
      Akt are in preclinical development. Another class of agents indirectly affect
      aberrant signaling, including inhibitors of chaperones and proteasomes. Several
      targeted agents seem to enhance the cytotoxicity of chemotherapy in preclinical
      models. The mechanism by which signaling inhibition might synergize with
      chemotherapy requires more study so that rational combinations move forward. Very
      few targeted agents have been studied rigorously in this fashion.

PMID- 16609061
TI  - Targeting the mitogen-activated protein kinase pathway in the treatment of
      malignant melanoma.
AB  - The mitogen-activated protein kinase (MAPK; i.e., Ras-Raf-Erk) pathway is an
      attractive target for therapeutic intervention in melanoma due to its integral
      role in the regulation of proliferation, invasiveness, and survival and the
      recent availability of pharmaceutical agents that inhibit the various kinases and
      GTPases that comprise the pathway. Genetic studies have identified activating
      mutations in either B-raf or N-ras in most cutaneous melanomas. Other studies
      have delineated the contribution of autocrine growth factors (e.g., hepatocyte
      growth factor and fibroblast growth factor) to MAPK activation in melanoma.
      Still, others have emphasized the consequences of the down-modulation of
      endogenous raf inhibitors, such as Sprouty family members (e.g., SPRY2) and raf-1
      kinase inhibitory protein, in the regulation of the pathway. The diversity of
      molecular mechanisms used by melanoma cells to ensure the activity of the MAPK
      pathway attests to its importance in the evolution of the disease and the
      likelihood that inhibitors of the pathway may prove to be highly effective in
      melanoma treatment. MAPK inhibition has been shown to result in the
      dephosphorylation of the proapoptotic Bcl-2 family members Bad and Bim. This
      process in turn leads to caspase activation and, ultimately, the demise of
      melanoma cells through the induction of apoptosis. Several recent studies have
      identified non-mitogen-activated protein/extracellular signal-regulated kinase
      kinase-binding partners of raf and suggested that the prosurvival effects of raf
      and the lethality of raf inhibition are mediated through these alternative
      targets, independent of the MAPK pathway. Other studies have suggested that
      endothelial cells are the primary targets of raf inhibitors in vivo and that the
      antitumor effect of these agents are largely attributable to angiogenesis
      inhibition. This article reviews the genetic and biochemical factors contributing
      to MAPK activation in melanoma, the mechanisms by which inhibition of the pathway
      might prove deleterious to tumor cells, and the potential of MAPK inhibitors in
      the treatment of the disease.

PMID- 16609062
TI  - Molecular targets in melanoma from angiogenesis to apoptosis.
AB  - Angiogenesis is a hallmark of melanoma progression. Antiangiogenic agents have
      been infrequently tested in patients with advanced melanoma. Experience with most
      other cancers suggests that single-agent application of angiogenic inhibitors is
      unlikely to have substantial clinical antitumor activity in melanoma. It is more
      likely that combinations of antiangiogenic agents with either chemotherapy or
      other targeted therapy will be needed to produce significant clinical benefit. In
      melanoma, numerous cellular pathways important to cell proliferation, apoptosis,
      or metastases have recently been shown to be activated. Activation occurs through
      specific mutations (B-RAF, N-RAS, and PTEN) or changes in expression levels of
      various proteins (PTEN, BCL-2, NF-kappaB, CDK2, and cyclin D1). Agents that block
      these pathways are rapidly entering the clinical setting, including RAF
      inhibitors (sorafenib), mitogen-activated protein kinase inhibitors (PD0325901),
      mammalian target of rapamycin inhibitors (CCI-779), and farnesyl transferase
      inhibitors (R115777) that inhibit N-RAS and proteasome inhibitors (PS-341) that
      block activation of nuclear factor-kappaB (NF-kappaB). It will be a challenge to
      evaluate these agents alone, in combination with each other, or with chemotherapy
      in patients with melanoma. Trials with large populations of biologically ill
      defined tumors run the risk of missing clinical antitumor activity that is
      important for a particular yet-to-be-defined subset of patients. To rationally
      and optimally develop these targeted agents, it will be critical to adequately
      test for the presence of the presumed cellular target in tumor specimens and the
      effect of therapy on the proposed target (biological response). Investigators in
      this field will need to carefully plan these trials so that at the end of the
      day, we learn from both the failures and successes of targeted therapy.

PMID- 16609063
TI  - Cell-surface association between matrix metalloproteinases and integrins: role of
      the complexes in leukocyte migration and cancer progression.
AB  - Leukocyte motility is known to be dependent on both beta2-integrins and matrix
      metalloproteinases MMP-2/-9 or gelatinases, which mediate leukocyte adhesion and
      the proteolysis needed for invasion, respectively. Gelatinases not only play an
      important role in cell migration, tissue remodeling, and angiogenesis during
      development, but are also involved in the progression and invasiveness of many
      cancers, including leukemias. The concept that MMPs associate with integrins, as
      well as their importance in some physiologic and pathologic conditions, has been
      advanced previously but has not been examined on leukocytes. This review will
      examine mainly the function of the MMP-integrin complexes in normal leukocyte
      migration and the effect of integrin and broad-spectrum MMP inhibitors in tumor
      progression.

PMID- 16609064
TI  - Lenalidomide therapy in myelofibrosis with myeloid metaplasia.
AB  - We present results of 2 similarly designed but separate phase 2 studies involving
      single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with
      symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment
      consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count <
      100 x 10(9)/L) for 3 to 4 months with a plan to continue treatment for either 3
      or 24 additional months, in case of response. Overall response rates were 22% for
      anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia
      was deemed impressive in 8 patients whose hemoglobin level normalized from a
      baseline of either transfusion dependency or hemoglobin level lower than 100 g/L.
      Additional treatment effects in these patients included resolution of
      leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and
      angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied
      by a reduction in JAK2(V617F) mutation burden (1 patient). Grade 3 or 4 adverse
      events included neutropenia (31%) and thrombocytopenia (19%). We conclude that
      lenalidomide engenders an intriguing treatment activity in a subset of patients
      with MMM that includes an unprecedented effect on peripheral blood and bone
      marrow abnormalities.

PMID- 16609065
TI  - The Steap proteins are metalloreductases.
AB  - Iron and copper are essential for all organisms, assuming critical roles as
      cofactors in many enzymes. In eukaryotes, the transmembrane transport of these
      elements is a highly regulated process facilitated by the single electron
      reduction of each metal. Previously, we identified a mammalian ferrireductase,
      Steap3, critical for erythroid iron homeostasis. Now, through homology,
      expression, and functional studies, we characterize all 4 members of this protein
      family and demonstrate that 3 of them, Steap2, Steap3, and Steap4, are not only
      ferrireductases but also cupric reductases that stimulate cellular uptake of both
      iron and copper in vitro. Finally, the pattern of tissue expression and
      subcellular localization of these proteins suggest they are physiologically
      relevant cupric reductases and ferrireductases in vivo.

PMID- 16609067
TI  - FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy
      for diffuse large B-cell lymphoma.
AB  - The precise mechanism of rituximab plus
      cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) therapy in diffuse
      large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2
      mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which
      is activated by effector cells via immunoglobulin G (IgG) fragment C receptors
      (FcRs), was also proposed as a mechanism of rituximab. The current study
      evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for
      DLBCL with the basis that FcR polymorphism can affect rituximab's affinity for
      ADCC effector cells. The FCGR3A and FCGR2A gene polymorphisms were determined in
      DLBCL patients receiving R-CHOP (n = 113) compared with CHOP therapy (n = 85).
      The FCGR3A valine (V) allele was significantly correlated with a higher complete
      response rate to R-CHOP compared with the phenylalanine (F) allele (88% in V/V vs
      79% in V/F vs 50% in F/F; P = .002), while no difference was found between FCGR2A
      polymorphisms. In addition, V/V allele was associated with faster achievement of
      response than other alleles. The impact of the FCGR3A gene polymorphism on
      response rate was not noted in the CHOP group. In terms of overall or event-free
      survival, no difference was found according to FCGR3A or FCGR2A alleles. The
      FCGR3A single nucleotide polymorphism (SNP) is predictive of response to R-CHOP,
      but does not correlate with survival in patients with DLBCL.

PMID- 16609068
TI  - The p67 laminin receptor identifies human erythroid progenitor and precursor
      cells and is functionally important for their bone marrow lodgment.
AB  - The laminins are a group of extracellular matrix proteins with constitutive
      expression in all tissues, including bone marrow stroma. A functional role for
      the nonintegrin laminin receptor p67 has been described for cancer metastasis and
      lymphocyte trafficking. Expression of p67 was also reported for other subsets of
      mature leukocytes and for malignant hematopoietic or nonhematopoietic cells. We
      explored p67 expression on normal hematopoietic progenitor cells (HPCs) and its
      putative role in bone marrow retention of transplanted HPCs. We found p67
      expression on a subset of primary human CD34(+) cells coexpressing erythroid
      markers. Of importance, p67 recognizes early erythroid progenitors, since sorted
      p67(+) cells were significantly enriched for burst-forming units-erythroid (BFU
      Es) and depleted of colony-forming units--granulocyte/macrophage (CFU-GMs).
      Blockade of p67 binding of donor cells, using antifunctional antibody, reduced
      bone marrow homing of BFU-Es. These studies identify p67 as a novel phenotypic
      marker for erythroid HPCs of functional importance for lineage-specific
      homing/retention among adult transplanted HPCs.

PMID- 16609069
TI  - Intrathecal triple therapy decreases central nervous system relapse but fails to
      improve event-free survival when compared with intrathecal methotrexate: results
      of the Children's Cancer Group (CCG) 1952 study for standard-risk acute
      lymphoblastic leukemia, reported by the Children's Oncology Group.
AB  - The Children's Cancer Group (CCG) 1952 clinical trial for children with standard
      risk acute lymphoblastic leukemia (SR-ALL) compared intrathecal (IT) methotrexate
      (MTX) with IT triples (ITT) (MTX, cytarabine, and hydrocortisone sodium succinate
      [HSS]) as presymptomatic central nervous system (CNS) treatment. Following
      remission induction, 1018 patients were randomized to receive IT MTX and 1009
      ITT. Multivariate analysis identified male sex, hepatomegaly, CNS-2 status, and
      age younger than 2 or older than 6 years as significant predictors of isolated
      CNS (iCNS) relapse. The 6-year cumulative incidence estimates of iCNS relapse are
      3.4% +/- 1.0% for ITT and 5.9% +/- 1.2% for IT MTX; P = .004. Significantly more
      relapses occurred in bone marrow (BM) and testicles with ITT than IT MTX,
      particularly among patients with T-cell phenotype or day 14 BM aspirate
      containing 5% to 25% blasts. Thus, the estimated 6-year event-free survivals
      (EFS) with ITT or IT MTX are equivalent at 80.7% +/- 1.9% and 82.5% +/- 1.8%,
      respectively (P = .3). Because the salvage rate after BM relapse is inferior to
      that after CNS relapse, the 6-year overall survival (OS) for ITT is 90.3% +/-
      1.5% versus 94.4% +/- 1.1% for IT MTX (P = .01). It appears that ITT improves
      presymptomatic CNS treatment but does not improve overall outcome.

PMID- 16609071
TI  - Natural history of cerebral vein thrombosis: a systematic review.
AB  - Cerebral vein thrombosis (CVT) has been considered, until a few years ago, an
      uncommon disease with significant long-term morbidity and high mortality rate.
      New noninvasive diagnostic techniques have increased the frequency with which
      this disease is diagnosed; despite this, there continues to be little data on its
      natural history. The objectives of this study were to evaluate the mortality
      rate, the rate of disability at long-term follow-up, and the incidence of
      recurrence after a first episode of CVT; to determine clinical and radiologic
      predictors of death and dependence; and to identify possible risk factors for
      recurrence. ( DATA SOURCE: MEDLINE and EMBASE databases, reference lists of
      selected articles and authors' libraries.) Nineteen studies were identified.
      Mortality rate during peri-hospitalization period is 5.6% (range, 0%-15.2%) and
      9.4% (range, 0%-39%) at the end of follow-up period. Eighty-eight percent of
      surviving patients recover completely or have only a mild functional or cognitive
      deficit. Two thirds of patients with CVT recanalized within the first few months
      after presentation, and 2.8% (range, 0%-11.7%) had objectively confirmed
      recurrence. We conclude that patients with CVT have a low risk of death and that
      most patients have a good long-term prognosis.

PMID- 16609072
TI  - Clinical application and proposal for modification of the International Working
      Group (IWG) response criteria in myelodysplasia.
AB  - The myelodysplastic syndromes (MDSs) are heterogeneous with respect to clinical
      characteristics, pathologic features, and cytogenetic abnormalities. This
      heterogeneity is a challenge for evaluating response to treatment. Therapeutic
      trials in MDS have used various criteria to assess results, making cross-study
      comparisons problematic. In 2000, an International Working Group (IWG) proposed
      standardized response criteria for evaluating clinically significant responses in
      MDS. These criteria included measures of alteration in the natural history of
      disease, hematologic improvement, cytogenetic response, and improvement in health
      related quality of life. The relevance of the response criteria has now been
      validated prospectively in MDS clinical trials, and they have gained acceptance
      in research studies and in clinical practice. Because limitations of the IWG
      criteria have surfaced, based on practical and reported experience, some
      modifications were warranted. In this report, we present recommendations for
      revisions of some of the initial criteria.

PMID- 16609073
TI  - Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide
      synthase expression by inhibiting p52 acetylation and binding.
AB  - Melatonin has been shown to be produced by nonpineal cells and possess anti
      inflammatory actions in animal models. In the present study, we tested the
      hypothesis that melatonin suppresses the expression of proinflammatory genes such
      as cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (INOS) by a common
      transcriptional mechanism. Melatonin but not tryptophan or serotonin inhibited
      lipopolysaccharide (LPS)-induced COX-2 and iNOS protein levels and promoter
      activities in RAW 264.7 cells in a time- and concentration-dependent manner. LPS
      or LPS plus interferon-gamma (IFNgamma) increased binding of all 5 isoforms of NF
      kappaB to COX-2 and iNOS promoters. Melatonin selectively inhibited p52 binding
      without affecting p100 expression, p52 generation from p100, or p52 nuclear
      translocation. p52 acetylation was enhanced by LPS, which was abrogated by
      melatonin. Melatonin inhibited p300 histone acetyltransferase (HAT) activity and
      abrogated p300-augmented COX-2 and iNOS expression. HAT inhibitors suppressed LPS
      induced p52 binding and acetylation to an extent similar to melatonin, and
      melatonin did not potentiate the effect of HAT inhibitors. These results suggest
      that melatonin inhibits COX-2 and iNOS transcriptional activation by inhibiting
      p300 HAT activity, thereby suppressing p52 acetylation, binding, and
      transactivation.

PMID- 16609075
TI  - A piece of my mind. Last words.

PMID- 16609074
TI  - The cover. The Midnight Ride of Paul Revere.

PMID- 16609076
TI  - Researchers focus on improving treatments for acute ischemic stroke.

PMID- 16609077
TI  - Antidepressants and pregnancy: weighing risks and benefits no easy task.

PMID- 16609078
TI  - NIH initiatives to probe contribution of genes, environment in disease.

PMID- 16609079
TI  - Supplemental oxygen and risk of surgical wound infection.

PMID- 16609080
TI  - Supplemental oxygen and risk of surgical wound infection.

PMID- 16609081
TI  - Supplemental oxygen and risk of surgical wound infection.

PMID- 16609082
TI  - Relations between physicians and attorneys.

PMID- 16609083
TI  - Relations between physicians and attorneys.

PMID- 16609084
TI  - Relations between physicians and attorneys.

PMID- 16609085
TI  - Constraints on publication rights in industry-initiated clinical trials.

PMID- 16609086
TI  - Effects of conjugated equine estrogens on breast cancer and mammography screening
      in postmenopausal women with hysterectomy.
AB  - CONTEXT: The Women's Health Initiative Estrogen-Aone trial comparing conjugated
      equine estrogens (CEE) with placebo was stopped early because of an increased
      stroke incidence and no reduction in risk of coronary heart disease. Preliminary
      results suggesting possible reduction in breast cancers warranted more detailed
      analysis. OBJECTIVE: To determine the effects of CEE on breast cancers and
      mammographic findings. DESIGN, SETTING, AND PARTICIPANTS: Following breast cancer
      risk assessment, 10,739 postmenopausal women aged 50 to 79 years with prior
      hysterectomy were randomized to CEE or placebo at 40 US clinical centers from
      1993 through 1998. Mammography screenings and clinical breast examinations were
      performed at baseline and annually. All breast cancers diagnosed through February
      29, 2004, are included. INTERVENTION: A dose of 0.625 mg/d of CEE or an identical
      appearing placebo. MAIN OUTCOME MEASURES: Breast cancer incidence, tumor
      characteristics, and mammogram findings. RESULTS: After a mean (SD) follow-up of
      7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned
      to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09)
      with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases
      in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95%
      CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test
      for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of
      women in the CEE group had mammograms with abnormalities requiring follow-up vs
      5.5% in the placebo group (P<.001), a pattern that continued through the trial to
      reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however,
      this difference was primarily in assessments requiring short interval follow-up.
      CONCLUSIONS: Treatment with CEE alone for 7.1 years does not increase breast
      cancer incidence in postmenopausal women with prior hysterectomy. However,
      treatment with CEE increases the frequency of mammography screening requiring
      short interval follow-up. Initiation of CEE should be based on consideration of
      the individual woman's potential risks and benefits. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00000611.

PMID- 16609087
TI  - Estrogen-receptor status and outcomes of modern chemotherapy for patients with
      node-positive breast cancer.
AB  - CONTEXT: Breast cancer estrogen-receptor (ER) status is useful in predicting
      benefit from endocrine therapy. It may also help predict which patients benefit
      from advances in adjuvant chemotherapy. OBJECTIVE: To compare differences in
      benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER
      positive tumors. DESIGN, SETTING, AND PATIENTS: Trial data from the Cancer and
      Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER
      status compared using hazards over time and multivariate models. Randomized
      trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and
      fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent
      with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April
      1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with
      concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3
      week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node
      positive breast cancer patients received adjuvant treatment. MAIN OUTCOME
      MEASURES: Disease-free and overall survival. RESULTS: For ER-negative tumors,
      chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%,
      and 23% in the 3 studies, respectively, and 55% comparing the lowest dose in the
      first study with biweekly cycles in the third study. Corresponding relative risk
      reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8% in
      the 3 studies, and 26% overall. The overall mortality rate reductions associated
      with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive
      patients, respectively. All individual ER-negative comparisons and no ER-positive
      comparisons were statistically significant. Absolute benefits due to chemotherapy
      were greater for patients with ER-negative compared with ER-positive tumors:
      22.8% more ER-negative patients survived to 5 years disease-free if receiving
      chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for
      overall survival were 16.7% vs 4.0%. CONCLUSION: Among patients with node
      positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide
      plus paclitaxel lowers the rate of recurrence and death by more than 50% in
      comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used
      in the first study.

PMID- 16609088
TI  - Invasive pneumococcal disease among infants before and after introduction of
      pneumococcal conjugate vaccine.
AB  - CONTEXT: Streptococcus pneumoniae is a serious infection in young infants. A
      heptavalent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 and
      recommended for all children aged 2 to 23 months. OBJECTIVE: To determine the
      rates of invasive pneumococcal disease (IPD) in young infants before and after
      PCV7 was incorporated into the childhood immunization schedule in June 2000.
      DESIGN, SETTING, AND PARTICIPANTS: A prospective, population-based study of
      infants aged 0 to 90 days who resided in areas in 8 US states with active
      laboratory surveillance for invasive S pneumoniae infections from July 1, 1997,
      to June 30, 2004. MAIN OUTCOME MEASURES: Rates of laboratory-confirmed IPD before
      (July 1, 1997-June 30, 2000) and after (July 1, 2001-June 30, 2004) PCV7
      introduction, excluding a transition year (July 1, 2000-June 30, 2001). RESULTS:
      There were 146 cases of IPD, 89 before and 57 after PCV7 introduction. Isolated
      bacteremia occurred in 94 cases (64%), pneumonia in 27 (18%), meningitis in 22
      (15%), and septic arthritis and/or osteomyelitis in 3 (2%). Mean rates of IPD for
      infants aged 0 to 90 days decreased 40% from 11.8 (95% confidence interval [CI],
      9.6-14.5) to 7.2 (95% CI, 5.6-9.4; P = .004) per 100 000 live births following
      PCV7 introduction. Among black infants, mean rates of IPD decreased significantly
      from 17.1 (95% CI, 11.9-24.6) to 5.3 (95% CI, 2.8-10.1; P = .001) per 100,000
      live births, with a nonsignificant decrease from 9.6 (95% CI, 7.3-12.7) to 6.8
      (95% CI, 4.9-9.4) per 100,000 live births for white infants. Rates of PCV7
      serotype isolates decreased significantly from 7.3 (95% CI, 5.3-10.1) to 2.4 (95%
      CI, 1.6-3.8; P<.001) per 100,000 live births, while rates of non-PCV7 serotypes
      remained stable (P = .55). CONCLUSIONS: Since PCV7 introduction, rates of IPD in
      young infants have decreased significantly, providing evidence that vaccinating
      children aged 2 to 23 months has led to changes in pneumococcal carriage in
      infants too young to receive PCV7. With a significant decrease in rates of IPD
      among black infants, the previous racial difference has been eliminated.

PMID- 16609089
TI  - Effect of blinded peer review on abstract acceptance.
AB  - CONTEXT: Peer review should evaluate the merit and quality of abstracts but may
      be biased by geographic location or institutional prestige. The effectiveness of
      blinded peer review at reducing bias is unknown. OBJECTIVE: To evaluate the
      effect of blinded review on the association between abstract characteristics and
      likelihood of abstract acceptance at a national research meeting. DESIGN AND
      SETTING: All abstracts submitted to the American Heart Association's annual
      Scientific Sessions research meeting from 2000-2004. Abstract review included the
      author's name and institution (open review) from 2000-2001, and this information
      was concealed (blinded review) from 2002-2004. Abstracts were categorized by
      country, primary language, institution prestige, author sex, and government and
      industry status. MAIN OUTCOME MEASURE: Likelihood of abstract acceptance during
      open and blinded review, by abstract characteristics. RESULTS: The mean number of
      abstracts submitted each year for evaluation was 13,455 and 28.5% were accepted.
      During open review, 40.8% of US and 22.6% of non-US abstracts were accepted
      (relative risk [RR], 1.81; 95% confidence interval [CI], 1.75-1.88), whereas
      during blinded review, 33.4% of US and 23.7% of non-US abstracts were accepted
      (RR, 1.41; 95% CI, 1.37-1.45; P<.001 for comparison between peer review periods).
      Among non-US abstracts, during open review, 31.1% from English- speaking
      countries and 20.9% from non-English-speaking countries were accepted (RR, 1.49;
      95% CI, 1.39-1.59), whereas during blinded review, 28.8% and 22.8% of abstracts
      were accepted, respectively (RR, 1.26; 95% CI, 1.19-1.34; P<.001). Among
      abstracts from US academic institutions, during open review, 51.3% from highly
      prestigious and 32.6% from nonprestigious institutions were accepted (RR, 1.57;
      95% CI, 1.48-1.67), whereas during blinded review, 38.8% and 29.0% of abstracts
      were accepted, respectively (RR, 1.34; 95% CI, 1.26-1.41; P<.001). CONCLUSIONS:
      This study provides evidence of bias in the open review of abstracts, favoring
      authors from the United States, English-speaking countries outside the United
      States, and prestigious academic institutions. Moreover, blinded review at least
      partially reduced reviewer bias.

PMID- 16609090
TI  - Activation of oxidative stress by acute glucose fluctuations compared with
      sustained chronic hyperglycemia in patients with type 2 diabetes.
AB  - CONTEXT: Glycemic disorders, one of the main risk factors for cardiovascular
      disease, are associated with activation of oxidative stress. OBJECTIVE: To assess
      the respective contributions of sustained chronic hyperglycemia and of acute
      glucose fluctuations to oxidative stress in type 2 diabetes. DESIGN, SETTING, AND
      PARTICIPANTS: Case-control study of 21 patients with type 2 diabetes (studied
      2003-2005) compared with 21 age- and sex-matched controls (studied in 2001) in
      Montpellier, France. MAIN OUTCOME MEASURES: Oxidative stress, estimated from 24
      hour urinary excretion rates of free 8-iso prostaglandin F2alpha (8-iso
      PGF2alpha). Assessment of glucose fluctuations was obtained from continuous
      glucose monitoring system data by calculating the mean amplitude of glycemic
      excursions (MAGE). Postprandial contribution to glycemic instability was assessed
      by determining the postprandial increment of glucose level above preprandial
      values (mean postprandial incremental area under the curve [AUCpp]). Long-term
      exposure to glucose was estimated from hemoglobin A1c, from fasting glucose
      levels, and from mean glucose concentrations over a 24-hour period. RESULTS: Mean
      (SD) urinary 8-iso PGF2alpha excretion rates were higher in the 21 patients with
      diabetes (482 [206] pg/mg of creatinine) compared with controls (275 [85] pg/mg
      of creatinine). In univariate analysis, only MAGE (r = 0.86; P<.001) and AUCpp (r
      = 0.55; P = .009) showed significant correlations with urinary 8-iso PGF2alpha
      excretion rates. Relationships between 8-iso PGF2alpha excretion rates and either
      MAGE or AUCpp remained significant after adjustment for the other markers of
      diabetic control in multiple linear regression analysis (multiple R2 = 0.72 for
      the model including MAGE and multiple R2 = 0.41 for the model including AUCpp).
      Standardized regression coefficients were 0.830 (P<.001) for MAGE and 0.700 (P =
      .003) for AUCpp. CONCLUSIONS: Glucose fluctuations during postprandial periods
      and, more generally, during glucose swings exhibited a more specific triggering
      effect on oxidative stress than chronic sustained hyperglycemia. The present data
      suggest that interventional trials in type 2 diabetes should target not only
      hemoglobin A1c and mean glucose concentrations but also acute glucose swings.

PMID- 16609091
TI  - Assessing glycemia in diabetes using self-monitoring blood glucose and hemoglobin
      A1c.
AB  - CONTEXT: With the increasing prevalence of diabetes, successful management of
      blood glucose control is increasingly important. Current approaches to assessing
      glycemia include the use of self-monitoring of blood glucose (SMBG) and
      hemoglobin A1c (HbA1c). OBJECTIVES: To assess the evidence underlying the use of
      these 2 modalities, to evaluate confounders and sources of error in each test, to
      describe upcoming developments, and to reach evidence-based conclusions on their
      optimal use. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Reports
      identified from MEDLINE searches (1976-2005) using relevant terms were selected
      for quality and relevance to the stated questions. Particular attention was paid
      to larger cohort studies, clinical trials, meta-analyses, and established
      recommendations. DATA SYNTHESIS: If used properly SMBG gives an acceptably
      accurate reflection of immediate plasma glucose levels. Study results vary, but
      in general, the evidence supports a positive effect of regular SMBG for improving
      glycemia, particularly in individuals treated with insulin. The best timing of
      SMBG and its frequency are controversial issues, but the clinical recommendation
      is for regular monitoring with frequency depending on the treatment and the
      instability of glycemia. In the relatively near term, SMBG could gradually be
      replaced by continuous glucose monitoring. HbA1c measures long-term glycemic
      control, reflecting a time-weighted mean over the previous 3 to 4 months. There
      are a number of physiologic and methodologic confounders that can affect HbA1c,
      but standardization of assays has been well established. The main value of HbA1c
      is its use as a predictor of diabetic complications and the proven effect of
      improved control of HbA1c on complication risk. A reasonable target value for
      HbA1c is less than 7%. A new method for measuring HbA1c may cause significant
      changes in the recommended levels, the numbers reported, and even the name of the
      test. CONCLUSION: Assessing glycemia in diabetes can be a challenge, but
      approaches are available that promote successful management of blood glucose and
      may thereby lead to a significant reduction in morbidity and mortality related to
      diabetes.

PMID- 16609092
TI  - Public health strategies for pandemic influenza: ethics and the law.

PMID- 16609093
TI  - Recent trials in hypertension: compelling science or commercial speech?

PMID- 16609094
TI  - Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic
      complications.

PMID- 16609100
TI  - JAMA patient page. Pneumococcal diseases.

PMID- 16609101
TI  - Are the "life-support" courses updated? An evaluation of their literature base.
AB  - BACKGROUND: As a condition of employment, many physicians practicing in the
      United States are mandated to remain current in their certification of some or
      all of the life-support courses. These courses reputedly set the standard of care
      by establishing nationally recognized paradigms of resuscitation. These courses'
      textbooks are revised and re-released at regular intervals. OBJECTIVES: To
      determine whether the source data for these texts are vigorously updated with
      each revision and whether there is an obvious literature-based impetus to release
      a new version. METHODS: A comparison was made of the years of the references
      contained within the three most recent textbook editions of the advanced cardiac
      life support (ACLS), advanced trauma life support, basic life support, and
      pediatric advanced life support courses. The years of the references were tallied
      for each text, and these tallies were compared both within and between the
      courses. Data were divided into three groups: group 1, references published
      before the previous versions' release; group 2, references published after
      previous versions' release; group 3, references dated within three years of the
      texts' release. RESULTS: There appears to be a large amount of overlap of group 1
      data throughout most of the course texts; the number of references in group 2 and
      3 varies greatly between and within these courses. CONCLUSIONS: With one
      exception (ACLS in 2003), the life-support courses appear to be based on similar
      reference sets for the last 7 to 11 years. There may be a reason other than an
      availability of a critical mass of new information that prompts the release of a
      new edition of these life-support courses.

PMID- 16609102
TI  - Predictors of on-call specialist response times in California emergency
      departments.
AB  - OBJECTIVES: To assess waiting times in emergency departments (EDs) for on-call
      specialist response and how these might vary by facility or neighborhood
      characteristics. Limited availability of on-call specialists is thought to
      contribute to ED overcrowding. METHODS: Direct observational data from a random
      sample of 1,798 patients visiting 30 California EDs during a six-month period
      provided specialist waiting times. The authors used multivariate logistic
      regression and survival analysis to analyze predictors of time to on-call
      specialists' telephone response. RESULTS: Eighty-six percent of on-call
      specialists who were paged responded by telephone within 30 minutes. Ten percent
      of specialists did not respond at all. After controlling for the annual
      percentage of nonurgent ED patients at each facility, near closure status, and
      hospital ownership status, for every 10,000 dollars increase in hospital zip code
      income, the odds of on-call specialist response within 30 minutes increased by
      123% (adjusted odds ratio = 2.23; 95% confidence interval = 1.24 to 4.02; p =
      0.01). CONCLUSIONS: Although the majority of on-call specialists met the federal
      recommendation of a 30-minute response, those in poor neighborhoods were less
      likely to do so. One in ten on-call specialists did not respond at all. State and
      federal policies should focus on making more funding available for on-call
      specialist panels in poor areas.

PMID- 16609103
TI  - Child witnesses and victims in homes with adult intimate partner violence.
AB  - OBJECTIVES: To determine demographics of children in homes to which police are
      called for intimate-partner violence (IPV) and to compare the relative risk of
      perpetrator versus victim for those who, as children, witnessed or were victims
      of IPV and sexual assault. METHODS: Data from Resources, Inc. Victim Assistance
      Unit yearly intake statistics for 2004 were accessed. In this city with a
      population of approximately 500,000 people, police will call for an on-site
      advocate intervention (a trained social worker) at their own discretion for the
      adult or child victims of IPV and for children witnessing IPV. The social worker
      collects data on victims, perpetrators of IPV, and child witnesses or victims at
      all police calls for IPV. Comparisons were made by using chi-square, relative
      risks (RRs), and 95% confidence intervals (95% CI). RESULTS: Police and advocates
      visited 2,038 homes for IPV calls; 2,617 children were in these homes. Of these
      children, 1,904 (76%) witnessed IPV, and 698 (27%) were victims themselves. Adult
      victims (31%) and perpetrators (41%) had high rates of having witnessed IPV when
      they were children. Perpetrators were more likely than victims to have witnessed
      IPV as a child (RR, 1.56; 95% CI = 1.37 to 1.78) and to have been a victim of IPV
      as a child (RR, 1.71; 95% CI = 1.49 to 1.96). CONCLUSIONS: In this study
      population, 76% of IPV households include children, and one third of these
      children also are victims of IPV. Perpetrators often were victims and witnesses
      of IPV when they were children. This suggests that a history of childhood IPV is
      common for perpetrators of IPV. Development of and research on interventions for
      child witnesses or victims of IPV is needed.

PMID- 16609104
TI  - Does functional decline prompt emergency department visits and admission in older
      patients?
AB  - BACKGROUND: Older patients may visit the emergency department (ED) when their
      illness affects their function. OBJECTIVES: To quantify the function of older ED
      patients, to assess whether functional decline (FD) had occurred, and to
      determine whether function contributes to the ED visit and hospital admission.
      METHODS: The authors performed an institutional review board-approved,
      prospective, cross-sectional study in a community teaching hospital ED. Eligible
      patients were older than 74 years of age, with an illness at least 48 hours old.
      Patients from a nursing facility and those without a proxy who were unable or
      unwilling to complete the questions were excluded. The Older Americans Resources
      and Services Questionnaire, which tests seven instrumental activities of daily
      living (IADL) and seven physical ADLs (PADL), was used. Data are presented as
      means or proportions with 95% confidence intervals (95% CI), and comparisons as
      95% CI for the difference between proportions. RESULTS: The authors enrolled 90
      patients (mean age, 81.6 yr [SD +/- 4.9], 40% male). Dependence in at least one
      IADL was reported by 68% (95% CI = 57% to 77%), and in at least one PADL by 61%
      (95% CI = 50% to 71%). Functional decline was reported by 74% (95% CI = 64% to
      83%). Two thirds of those with IADL decline and three quarters of those with PADL
      decline said that this contributed to their ED visit. Seventy-seven percent with,
      and 63% without, IADL decline were admitted (14% difference, 95% CI = -6.1% to
      33%). Seventy-nine percent with and 61% without PADL decline were admitted (18%
      difference, 95% CI = -1.4% to 38%). CONCLUSIONS: Functional decline is common in
      older ED patients and contributes to ED visits in older patients; its role in
      admission is unclear.

PMID- 16609105
TI  - Assault-injured adolescents presenting to the emergency department: causes and
      circumstances.
AB  - OBJECTIVES: To describe the causes and circumstances of conflict leading to
      assault injury among urban youth seeking care in the emergency department.
      METHODS: The authors conducted in-person and telephone interviews with a
      convenience sample of 143 youth aged 12-19 years presenting to two urban
      emergency departments with an interpersonal assault injury. Patients were
      interviewed about the nature and circumstances of their injury. Descriptive
      analysis was performed, including stratified analysis by gender, age (12-15 vs.
      16-19 years), and weapon use. RESULTS: Seventy percent of patients knew or knew
      of the person(s) who injured them; most were friends, classmates, or
      acquaintances. More than half of the injuries (56%) were related to a past
      disagreement. Among assaults related to a past disagreement, 33% of patients had
      previous arguments with their assailant, 16% had previous fights, and 14% had
      previous weapons threats. Twenty-nine percent had been previously threatened, and
      11% had previously threatened their assailant. Twenty-eight percent of patients
      believed they helped to cause the injury by provoking a fight or letting down
      their guard. Nearly two thirds (64%) believed there were things they could change
      to prevent future injury, including staying away from dangerous situations and
      bad influences or controlling their tempers. CONCLUSIONS: Most assault injuries
      among adolescents involved past disagreements with people they knew. Many injured
      youth were mutually involved in conflict before their injury. Over time, many
      victims and perpetrators may be interchangeable. These data may help inform
      emergency department-based interventions to prevent assault injury.

PMID- 16609106
TI  - National study on emergency department visits for transient ischemic attack, 1992
      2001.
AB  - OBJECTIVES: To describe the epidemiology of U.S. emergency department (ED) visits
      for transient ischemic attack (TIA) and to measure rates of antiplatelet
      medication use, neuroimaging, and hospitalization during a ten-year time period.
      METHODS: The authors obtained data from the 1992-2001 National Hospital
      Ambulatory Medical Care Survey. TIA cases were identified by having ICD-9 code
      435. RESULTS: From 1992 to 2001, there were 769 cases, representing 2,969,000 ED
      visits for TIA. The population rate of 1.1 ED visits per 1,000 U.S. population
      (95% CI = 0.92 to 1.30) was stable over time. TIA was diagnosed in 0.3% of all ED
      visits. Physicians administered aspirin and other antiplatelet agents to a small
      percentage of patients, and 42% of TIA patients (95% CI = 29% to 55%) received no
      medications at all in the ED. Too few data points existed to measure a
      statistically valid trend over time. Physicians performed computed tomography
      scanning in 56% (95% CI = 45% to 66%) of cases and performed magnetic resonance
      imaging (MRI) in < 5% of cases, and there was a trend toward increased imaging
      over time. Admission rates did not increase during the ten-year period, with 54%
      (95% CI = 42% to 67%) admitted. Regional differences were noted, however, with
      the highest admission rate found in the Northeast (68%). CONCLUSIONS: Between
      1992 and 2001, the population rate of ED visits for TIA was stable, as were
      admission rates (54%). Antiplatelet medications appear to be underutilized and to
      be discordant with published guidelines. Neuroimaging increased significantly.
      These findings may reflect the limited evidence base for the guidelines,
      educational deficits, or other barriers to guideline implementation.

PMID- 16609107
TI  - Laser-assisted anesthesia reduces the pain of venous cannulation in children and
      adults: a randomized controlled trial.
AB  - OBJECTIVES: Application of topical anesthetics before intravenous (IV)
      cannulation is effective yet limited by delayed transdermal absorption. The
      authors evaluated a handheld laser device to enhance topical anesthetic
      absorption by ablating the stratum corneum, the major barrier to drug absorption
      through the skin. The hypothesis was that laser-assisted anesthesia would reduce
      the pain of IV cannulation in emergency department (ED) patients. METHODS: This
      was a blinded, randomized, controlled trial. ED patients aged 1 year and older
      requiring nonemergent IV cannulation were included. Patients were randomized to
      pretreatment of the skin with laser or sham laser, and standardized venous
      cannulation was performed on the dorsum of the patients' hands or antecubital
      fossa. In the experimental group, the area over the target vein was pretreated
      with a lightweight, portable Er:YAG unit, with a fluence of 3.5 J/cm2, a pulse
      width of 600 microseconds, and a spot diameter of 6 mm. Lidocaine 4% cream was
      applied to the area immediately after laser application. Five minutes later, the
      cream was wiped off and a trained nurse inserted an IV catheter. In the control
      group, a sham laser and lidocaine were used. Pain of laser application and IV
      cannulation was recorded on age-appropriate pain scales; presence of infection or
      abnormal pigmentation was determined at one week. Pain of cannulation was
      compared using parametric and nonparametric tests. RESULTS: Sixty-one patients
      were randomized to laser (30) and sham (31) pretreatment. Mean (+/- SD) age was
      27 (+/- 21) years, 49% were female, and one half were children younger than 18
      years. The mean pain of IV cannulation was significantly less (mean difference,
      28.3 mm; 95% confidence interval = 17.9 to 38.7) in patients pretreated with the
      laser (10.0 mm; 95% confidence interval = 4.4 to 15.6) than with sham laser (38.3
      mm; 95% confidence interval = 29.3 to 42.2). The difference in children was also
      significant. Application of the laser was painless in most patients. No patient
      developed infection or abnormal pigmentation. CONCLUSIONS: Pretreatment of the
      skin with a laser device followed by a five-minute topical lidocaine 4%
      application reduces the pain of IV cannulation in ED adult and pediatric
      patients.

PMID- 16609108
TI  - The effect of a commercially available burn-cooling blanket on core body
      temperatures in volunteers.
AB  - BACKGROUND: Cooling of burns is one of the oldest therapies, yet there are
      concerns that excessive cooling may result in hypothermia. OBJECTIVES: To
      determine the effects of surface cooling with a commercially available cooling
      blanket on the core temperatures of volunteers and to test the ability of the
      cooling blanket to reduce water evaporation from plastic containers. The null
      hypothesis was that rectal temperatures would not be reduced by surface cooling
      and that the cooling blanket would reduce evaporative water loss. METHODS: This
      was a prospective, noncomparative, interventional study. Ten healthy adult
      volunteers were recruited. Subjects were completely unclothed, and their entire
      body (excluding the head) was circumferentially wrapped with a commercially
      available gel-soaked cooling blanket at room temperature. A rectal temperature
      probe was inserted, and continuous monitoring of vital signs was performed during
      a 30-minute period. In addition, six plastic containers were filled with 50 mL of
      room-temperature water, half of which were covered with the cooling blanket. The
      amount of water remaining within the containers was measured at hourly intervals
      over four hours. RESULTS: The subjects' mean age was 38 years; 50% were female.
      There were no significant changes in core body temperatures over time in any of
      the study subjects. Mean (95% confidence intervals [CI]) core temperatures at the
      beginning and at the end of the study period were 37.2 degrees C (95% CI = 37.0
      degrees C to 37.4 degrees C) and 37.3 degrees C (95% CI = 37.1 degrees C to 37.5
      degrees C), respectively. Water evaporation in the blanket-covered containers was
      less than in the uncovered containers. CONCLUSIONS: The authors conclude that
      covering healthy volunteers with a room temperature burn-cooling blanket for 30
      minutes does not result in hypothermia and that the cooling blanket reduces
      evaporative water loss.

PMID- 16609111
TI  - A look at psychiatric education.

PMID- 16609112
TI  - Commentary on "A neurosciences-in-psychiatry curriculum project for medical
      students".

PMID- 16609113
TI  - The psychiatry clerkship: a position statement on the length of the psychiatry
      clerkship.

PMID- 16609114
TI  - Clinical grading in psychiatric clerkships.
AB  - OBJECTIVE: The clinical grade assessment is the most frequently used and heavily
      weighted component in the overall assessment of U.S. psychiatry clerkship
      students, yet the topic is understudied. The authors aimed to learn more about
      the nature, perceived virtues, and deficiencies of the clinical grade evaluation.
      METHODS: A 26-item questionnaire regarding the psychiatry clerkship clinical
      grading form was distributed to the clerkship directors of 129 medical schools in
      the U.S. and U.S. territories. The design of the document, its strengths, its
      weaknesses, grading outcomes, and utilization were assessed. RESULTS: Trends
      regarding clinical grading in psychiatry clerkships were detected. The clerkship
      grade form similarities, differences, desirable features, and utilization were
      ascertained, as were areas for improvement. CONCLUSIONS: The search for an
      optimal clinical grading process for the thousands of third-year medical students
      rotating annually is formidable. However, collaboration among psychiatry
      clerkship directors on development and improvement of clinical evaluation forms
      can clarify learning objectives and lead to better clinical evaluation tools.

PMID- 16609115
TI  - An approach to address grade inflation in a psychiatry clerkship.
AB  - OBJECTIVE: Universally, clerkship grading is diverse and not standardized. The
      authors' faculty was troubled by the inability to provide meaningful evaluations,
      as more than 60% of students received the highest grade. Although a psychiatry
      clerkship mandate of a faculty-observed student clinical interview existed for
      several years, the majority of students reported not completing the interview
      under direct observation by a faculty member, and no meaningful feedback or
      evaluation for this activity existed. In order to create diversity in grading
      criteria and to examine clinical skills more thoroughly than previously, written
      and oral examinations were developed and supervised interviews of patients and
      written comprehensive psychiatric evaluations were added. A core group of
      department faculty was instructed in the use of materials and instruments
      designed to standardize the experiences and the student evaluations. RESULTS:
      Adding a wider diversity of experiences and evaluations to the clerkship,
      particularly assessment of interviewing skills, oral exams, and evaluation of
      comprehensive histories, has resulted in a more divergent spread of grades.
      CONCLUSION: Clerkship grades can be effectively computed using various methods to
      examine knowledge and clinical skills. The addition of new methods of evaluation
      has added specificity to the performance feedback provided to the students
      completing the psychiatric clerkship. These changes have been viewed positively
      by department faculty and medical students. While requiring further refinement,
      they may eventually provide data to identify students requiring special attention
      in specific cognitive, relational, and clinical skill areas.

PMID- 16609116
TI  - Timing bias in the psychiatry subject examination of the National Board of
      Medical Examiners.
AB  - OBJECTIVE: The authors investigate whether the timing of the psychiatry clerkship
      influences scores on the National Board of Medical Examiners (NBME) subject exam
      as has been reported for other clerkships. The authors attempt to identify which
      clerkships, if any, offer an advantage when taken before psychiatry. METHODS:
      Mean aggregate exam scores over 4 years were calculated according to clerkship
      sequence. An analysis of variance was conducted to assess the effect of sequence
      on test scores. Pairwise comparisons (t tests) were performed to determine
      whether students who completed one particular clerkship before psychiatry scored
      higher on the subject examination than students who completed the clerkship after
      psychiatry. RESULTS: Students who take psychiatry near the end of the clerkship
      sequence score higher than students who take psychiatry as a first clerkship. The
      differences are small but significant. The mean score for students taking
      psychiatry first was 72.81, compared to a score of 78.51 for students taking the
      clerkship last. No single clerkship is more likely than another to increase test
      scores when taken before psychiatry. CONCLUSIONS: Clerkship directors must be
      aware of the timing bias in subject exam scores. However, the bias may not be
      sufficient to justify abandoning use of the subject examinations.

PMID- 16609117
TI  - Psychiatry in Medicine: five years of experience with an innovative required
      fourth-year medical school course.
AB  - OBJECTIVE: The author reports on a required fourth-year course, Psychiatry in
      Medicine, which was started in 1999 at Stony Brook Medical School. The aim was to
      address two important concerns in medical education at Stony Brook and throughout
      the United States: 1) the failure to recognize psychiatric pathology in
      outpatient medical settings and 2) the lack of education about psychosomatic
      medicine. METHODS: Details about the creation, implementation, and content of the
      course are presented, along with student evaluations and assessment after 5
      years. RESULTS: Eighty five percent of students felt the course would benefit
      their careers, and they indicated that their clinical behavior would be changed
      by the course. CONCLUSIONS: Findings indicate that it is both viable and valuable
      for medical schools to create courses similar to Psychiatry in Medicine. It is
      argued that the fourth year is especially fertile ground for such a course.

PMID- 16609118
TI  - Recruiting and rewarding faculty for medical student teaching.
AB  - OBJECTIVE: Finding time to teach psychiatry has become increasingly difficult.
      Concurrently, changes in medical student education are elevating demands for
      teaching. Academic psychiatry is challenged by these pressures to find innovative
      ways to recruit, retain, and reward faculty for teaching efforts. To address this
      challenge, the authors recommend a multifactorial approach to meeting the medical
      student educational mission of psychiatry departments. METHODS: This approach
      includes a variety of efforts including having Chairs serve as role models,
      enforcing the service requirements of volunteer faculty, expanding teaching
      venues, providing faculty development, elevating the status of teaching through
      academies, attending to promotion of faculty educators, establishing and
      nominating faculty for teaching awards, and using medical center resources to
      provide rewards for teachers. CONCLUSION: Academic leaders must acknowledge the
      inherent value of teaching to the academic enterprise and delegate sufficient
      resources to recruit, retain, and reward educators for the essential work that
      they perform.

PMID- 16609119
TI  - "How am I doing?": many problems but few solutions related to feedback delivery
      in undergraduate psychiatry education.
AB  - OBJECTIVE: Giving performance feedback to students in psychiatry requires
      particular delicacy and skill since a critique of the subjective artistry of the
      psychiatric interview may be felt more personally than a critique of an objective
      skill, such as eliciting a reflex or applying a stethoscope to the chest. Thus,
      one would expect that psychiatrists 1) are adept at giving feedback and 2) have
      written about the nuances of feedback delivery in psychiatric education. After a
      curricular needs assessment in our program revealed that feedback delivery was
      being neglected at all levels of training, a review of the medical education
      literature was conducted to find explanations for preceptor difficulty with
      performance feedback delivery in undergraduate psychiatric education. METHOD: A
      qualitative content-analysis review of the PubMed and OVID literature on feedback
      delivery and medical education was conducted. RESULTS: Several articles were
      available on feedback delivery in medical education, but only one of the studies
      was specific to undergraduate psychiatric education. Several articles offered
      practical tips to address deficiencies in the feedback process, but there was
      little to no explanation for the reasons behind the deficiencies. CONCLUSIONS:
      Reasons for the challenges faced by medical students and teachers during feedback
      conversations have not been fully explored in the literature. In contrast to
      other areas of medicine, little has been written specifically about feedback to
      students in undergraduate psychiatric education. Although there are many
      resources to assist medical educators with feedback delivery skills, an
      understanding as to why physicians and students struggle with feedback
      conversations is needed. Reasons for the apparent disconnect between what should
      be happening and what is actually happening during feedback conversations with
      undergraduate psychiatry students need to be understood. The authors hypothesize
      causes for the problems with feedback delivery in undergraduate psychiatric
      education.

PMID- 16609120
TI  - The junior medical student psychiatry clerkship: curriculum, attitudes, and test
      performance.
AB  - OBJECTIVE: The third-year clerkship provides fundamental psychiatric training
      experience for medical students at Ohio State University. The authors aimed to
      assess students' attitudes toward this clerkship, as well as its quality and its
      relationship to standardized measures of performance. METHODS: Pre- and post
      surveys using Likert-type scales were conducted. RESULTS: The majority of
      students appeared to have favorable attitudes at the beginning of the clerkship,
      and students with initial neutral attitudes seemed to develop more favorable
      attitudes at the conclusion of the rotation. Students demonstrated definitive
      attitudes toward various curriculum components that were currently in place.
      CONCLUSION: These findings reaffirm that timing of the rotation is a critical
      factor in standardized test performance. Data from this baseline study were
      utilized to modify the existing clerkship experience. Further research is
      underway to determine its impact.

PMID- 16609121
TI  - Medical students' perceptions of psychiatry as a career choice.
AB  - OBJECTIVE: This study describes medical students' perceptions of the field of
      psychiatry and identifies the impact of those perceptions on their career choices
      in order to explore the questions: Are we as a field doing all that we can to
      enhance the educational experience of all medical students, regardless of their
      career preferences? What are the most appropriate ways to encourage interested
      medical students that would allow for more targeted recruitment efforts toward
      the most receptive students? METHODS: Third-year (n=131) and fourth-year medical
      students (n=117) at a northeastern, urban, private university medical school
      completed anonymous self-report questionnaires. Students rated the impact of
      intellectual interest, status, earning potential, healthcare reform, quality of
      life, satisfaction, and stress of working with psychiatric patients on their
      consideration of a psychiatric career. Respondents were then systematically
      divided into two groups: 1) those who considered psychiatry as a possible career
      choice and 2) those who did not. RESULTS: When compared to students who had been
      coded as "not seriously considering" a career in psychiatry, students coded as
      "seriously considering" gave significantly higher positive ratings to the field's
      intellectual content and quality of life. There were also significant differences
      between the groups regarding the satisfaction involved in working with
      psychiatric patients. Students from both groups were equally concerned about
      stress levels in the field. CONCLUSIONS: Acknowledging, discussing, and providing
      a context for stressful experiences during the psychiatry clerkship are likely to
      bring about productive approaches to improve recruitment into the field as well
      as to improve all students' psychiatric education.

PMID- 16609122
TI  - Use of clerkship learning objectives by members of the Association of Directors
      of Medical Student Education in Psychiatry.
AB  - OBJECTIVE: The authors aimed to determine the extent and use of the 1995
      psychiatry clerkship goals and objectives published by the Association of
      Directors of Medical Student Education in Psychiatry (ADMSEP) and to obtain
      members' guidance regarding their proposed revision. METHODS: ADMSEP members were
      surveyed regarding their awareness and current use of the objectives, their
      advantages and disadvantages, and suggestions for revision. RESULTS: Fifty-four
      of approximately 130 members returned surveys, including 60% of members who
      identified as clerkship directors. Ninety percent of respondents were aware of
      the objectives and 48% used them. Use was significantly related to years of
      ADMSEP membership. Those who used the objectives did so moderately or
      extensively, and 84% found them moderately to very useful. Reasons for nonuse
      were the employment of other objectives, unawareness of them, too lengthy/not
      user-friendly, and lack of resources to implement them. Comprehensiveness and
      specificity were cited as both their most useful aspects and their least useful
      aspects. The most frequently suggested revisions included prioritization, adding
      more clinical competencies, decreasing the total number, and developing
      supporting documents such as clinical cases, references, sample examinations, and
      a resource manual. Respondents held strongly favorable attitudes regarding the
      utility of learning objectives. CONCLUSION: The ADMSEP psychiatry clerkship
      learning objectives were widely but not uniformly used among members surveyed,
      and use is significantly related to years of membership. Respondents strongly
      favor using learning objectives and desire that a new iteration of the document
      be more user-friendly, oriented to competencies, and supported by resource
      materials.

PMID- 16609123
TI  - Trends in undergraduate medical education: clinical clerkship learning
      objectives.
AB  - OBJECTIVE: To assist and inform the process of revising learning objectives for
      the psychiatry clerkship, a comprehensive review of the current state of learning
      objectives endorsed by national specialty organizations for core clinical
      clerkships was undertaken. METHODS: National specialty organizations that have
      developed and endorsed clerkship learning objectives were identified and learning
      objectives and support materials were reviewed. RESULTS: All core clinical
      clerkships have learning objectives developed and endorsed by national specialty
      organizations. The format for organizing these learning objectives varies widely
      among specialties from lists of topics of interest to exhaustive curriculum
      resource guides. Most specialty clerkship learning objectives have undergone
      extensive revision since 2000 or are currently in the revision process.
      Comparisons and trends in specialty clerkship learning objectives and curriculum
      resources are discussed. CONCLUSIONS: Revision of psychiatry clerkship learning
      objectives will benefit from adoption of features utilized by other specialties,
      including: prioritizing objectives; emphasizing contextual learning and skills
      mastery; linking learning objectives to support resources such as clinical cases,
      recommendations for instructional methodology, assessment strategies, and
      performance expectations; and shifting the focus of undergraduate psychiatry
      education beyond the clerkship to the entire four-year curriculum.

PMID- 16609124
TI  - A neurosciences-in-psychiatry curriculum project for medical students.
AB  - OBJECTIVE: Incorporating new neuroscience findings relevant to psychiatry into
      the medical school curriculum is challenging, especially at the level of clinical
      learning. In this pilot project, third-year medical student volunteers in their
      required 8-week clerkship participated in an e-mail-based experience relating
      contemporary neuroscience to psychiatry. METHODS: A faculty preceptor guided
      participants using one of the participants' patient work-ups as a platform to
      explore questions related to the neurosciences. Participants were surveyed for
      follow up. RESULTS: Eleven of 13 eligible students agreed to participate in the
      study during one academic year. Data is qualitative, consisting of the responses
      of the students and the formulations and feedback of the preceptor as the project
      proceeded. CONCLUSION: Participants were successful in identifying symptom
      complexes in the sample history and in exploring their questions in the
      literature and with one another. The protocol is well-suited to distance
      learning, is relevant to psychiatric education, and is flexible in its
      application.

PMID- 16609125
TI  - Getting our own house in order: improving psychiatry education to medical
      students as a prelude to medical school education reform.
AB  - OBJECTIVE: The authors summarize efforts to revitalize psychiatry teaching to
      medical students at Harvard Medical School (HMS) in advance of a major overhaul
      of the medical school curriculum. METHODS: This preliminary report chronicles key
      challenges and the organization of the reform effort within the departments of
      psychiatry affiliated with the medical school. RESULTS: Based upon a
      comprehensive internal review of psychiatric education at the medical school, the
      HMS Psychiatry Executive Committee and psychiatry faculty concluded that
      psychiatry teaching was underresourced and lacked cohesion and consistent
      standards and expectations across clinical sites involved in psychiatry teaching.
      Through a willingness to identify and vigorously address deficiencies in medical
      student education within a large decentralized program, psychiatry has earned a
      reputation as an effective reform agent at the medical school. CONCLUSIONS:
      Psychiatry education improvements have strengthened our partnership with the
      medical school as it is undertaking major educational reform of its entire
      curriculum.

PMID- 16609126
TI  - Do the personalities of international and U.S. medical graduates in psychiatry
      differ? A preliminary study.
AB  - OBJECTIVE: To compare personality traits of psychiatry residents with various
      characteristics. METHOD: The authors administered Cloninger's personality
      inventory to residents at two schools. RESULTS: There were no trait differences
      between international medical graduates (IMGs) and U.S. medical graduates (USMGs)
      or those for whom psychiatry was a first or second choice. CONCLUSION: Perceived
      differences between IMG and USMG psychiatry residents appear unrelated to
      personality.

PMID- 16609127
TI  - Teaching medical students about personality disorders and psychotherapeutic
      principles: a resident pilot initiative.

PMID- 16609129
TI  - Complementary and alternative medicine for functional gastrointestinal disorders.
AB  - Patients suffering from functional gastrointestinal disorders are likely to
      search elsewhere when conventional therapies fail them. Enthusiasm for
      complementary and alternative medicine use and research is clearly growing.
      Studies of acupuncture and herbal therapy for functional gastrointestinal
      disorders in the Western literature have often been limited by poor study design
      but these interventions may have promise and are discussed here.

PMID- 16609128
TI  - Novel synthesis of O6-alkylguanine containing oligodeoxyribonucleotides as
      substrates for the human DNA repair protein, O6-methylguanine DNA
      methyltransferase (MGMT).
AB  - The human DNA repair protein O6-methylguanine DNA methyltransferase (MGMT)
      dealkylates mutagenic O6-alkylguanine lesions within DNA in an irreversible
      reaction which results in inactivation of the protein. MGMT also provides
      resistance of tumours to alkylating agents used in cancer chemotherapy and its
      inactivation is therefore of particular clinical importance. We describe a post
      DNA synthesis strategy which exploits the novel, modified base 2-amino-6
      methylsulfonylpurine and allows access for the first time to a wide variety of
      oligodeoxyribonucleotides (ODNs) containing O6-alkylguanines. One such ODN
      containing O6-(4-bromothenyl)guanine is the most potent inactivator described to
      date with an IC50 of 0.1 nM.

PMID- 16609130
TI  - Independent component analysis of the EEG: is this the way forward for
      understanding abnormalities of brain-gut signalling?

PMID- 16609132
TI  - Self-help interventions in irritable bowel syndrome.

PMID- 16609131
TI  - Glial regulation of neuronal plasticity in the gut: implications for clinicians.

PMID- 16609134
TI  - Editor's quiz: GI snapshot. Cholestatic hepatitis with marked thrombocytopenia.

PMID- 16609133
TI  - T regulatory cell suppression of colitis: the role of TGF-beta.

PMID- 16609135
TI  - Editor's quiz: GI snapshot. Copious amounts of ascites.

PMID- 16609136
TI  - New diagnostic imaging tools for inflammatory bowel disease.

PMID- 16609137
TI  - Editor's quiz: GI snapshot. An unusual cystic lesion of liver.

PMID- 16609138
TI  - Stratification by sex and subgroup is necessary for RCT on IBS.

PMID- 16609139
TI  - Infliximab as a treatment for systemic amyloidosis associated with Crohn's
      disease.

PMID- 16609140
TI  - Do baseline ALT levels predict complications of chronic hepatitis B?

PMID- 16609141
TI  - Dyspepsia is distinguishable from heartburn.

PMID- 16609142
TI  - Mannan binding lectin (MBL) gene polymorphisms are not associated with anti
      Saccharomyces cerevisiae (ASCA) in patients with Crohn's disease.

PMID- 16609143
TI  - Genomic organization, promoter activity, and expression of the human choline
      transporter-like protein 1.
AB  - Choline transporter-like (CTL) proteins of the CTL1 family are novel
      transmembrane proteins implicated in choline transport for phospholipid
      synthesis. In this study, we characterized the 5'-flanking region of the human
      (h)CTL1 gene and examined some of the possible mechanisms of its regulation,
      including promoter activity, splicing, and expression. The transcription start
      site of the hCTL1 gene was mapped by 5'-rapid amplification of cDNA ends (RACE),
      and the presence of two splice variants, hCTL1a and hCTL1b, was investigated
      using isoform-specific PCR and 3'-RACE. The hCTL1 promoter region of
      approximately 900 bp was isolated from MCF-7 human breast cancer cells. The
      promoter was TATA-less and driven by a long stretch of GC-rich sequence in
      accordance with widespread expression of hCTL1 at both mRNA and protein levels.
      Deletion analyses demonstrated that a very strong promoter is contained within
      500 bp of the transcription start site, and more upstream regions did not
      increase its activity. The core promoter that conferred the minimal transcription
      is within the -188/+27-bp region, and its activity varied in human breast cancer
      and mouse skeletal muscle cells. Multiple motifs within the promoter regulatory
      region bound nuclear factors from both cultured cells and normal human skeletal
      muscle. The motifs within the three regions [S1 (-92/-61 bp), S2 (-174/-145 bp),
      and S3 (-289/-260 bp)] contained overlapping binding sites for hematopoietic
      transcription factors and ubiquitous transcription factors, in line with the
      expected gene function. Genomic analyses demonstrated a high conservation of
      hCTL1 and mouse CTL1 proximal promoters. Accordingly, mRNA profiles demonstrated
      that human splice variants were expressed ubiquitously, as demonstrated for the
      mouse transcripts; however, they differed from the profiles of rat CTL1
      transcripts, which were more restricted to neurons and intestinal tissues. The
      shorter hCTL1b variant contained the cytosolic COOH-terminal motif L651KKR654 for
      endoplasmic reticulum retrieval/retention. This retention signal was conserved in
      hCTL1b and rat and mouse CTL1b and is typical for transmembrane proteins of type
      1 topology.

PMID- 16609144
TI  - Novel subcellular locations and functions for secretory pathway Ca2+/Mn2+
      ATPases.
AB  - Secretory pathway Ca2+/Mn2+-ATPases (SPCAs) are important for maintenance of
      cellular Ca2+ and Mn2+ homeostasis, and, to date, all SPCAs have been found to
      localize to the Golgi apparatus. The single Drosophila SPCA gene (SPoCk) was
      identified by an in silico screen for novel Ca2+-ATPases. It encoded three SPoCk
      isoforms with novel, distinct subcellular specificities in the endoplasmic
      reticulum (ER) and peroxisomes in addition to the Golgi. Furthermore, expression
      of the peroxisome-associated SPoCk isoform was sexually dimorphic. Overexpression
      of organelle-specific SPoCk isoforms impacted on cytosolic Ca2+ handling in both
      cultured Drosophila cells and a transporting epithelium, the Drosophila
      Malpighian (renal) tubule. Specifically, the ER isoform impacted on inositol
      trisphosphate-mediated Ca2+ signaling and the Golgi isoform impacted on diuresis,
      whereas the peroxisome isoform colocalized with Ca2+ "spherites" and impacted on
      calcium storage and transport. Interfering RNA directed against the common exons
      of the three SPoCk isoforms resulted in aberrant Ca2+ signaling and abolished
      neuropeptide-stimulated diuresis by the tubule. SPoCk thus contributed to both of
      the contrasting requirements for Ca2+ in transporting epithelia: to transport or
      store Ca2+ in bulk without compromising its use as a signal.

PMID- 16609145
TI  - Transgenic expression of CYP7A1 in LDL receptor-deficient mice blocks diet
      induced hypercholesterolemia.
AB  - Constitutive expression of a cholesterol-7alpha-hydroxylase (CYP7A1) transgene in
      LDL receptor-deficient mice blocked the ability of a cholesterol-enriched diet to
      increase plasma levels of apolipoprotein B-containing lipoproteins. LDL receptor
      deficient mice expressing the CYP7A1 transgene exhibited complete resistance to
      diet-induced hypercholesterolemia and to the accumulation of cholesterol in the
      liver. Hepatic mRNA expression of liver X receptor-inducible ABCG5 and ABCG8 was
      decreased in CYP7A1 transgenic, LDL receptor-deficient mice fed a cholesterol
      enriched diet. Thus, increased biliary cholesterol excretion could not account
      for the maintenance of cholesterol homeostasis. CYP7A1 transgenic, LDL receptor
      deficient mice fed the cholesterol-enriched diet exhibited decreased jejunal
      Niemann-Pick C1-Like 1 protein (NPC1L1) mRNA expression, an important mediator of
      intestinal cholesterol absorption. A taurocholate-enriched diet also decreased
      NPC1L1 mRNA expression in a farnesoid X receptor-independent manner. Reduced
      expression of NPC1L1 mRNA was associated with decreased cholesterol absorption (
      approximately 20%; P < 0.05) exhibited by CYP7A1 transgenic LDL receptor
      deficient mice fed the cholesterol-enriched diet. The combined data show that
      enhanced expression of CYP7A1 is an effective means to prevent the accumulation
      of cholesterol in the liver and of atherogenic apolipoprotein B-containing
      lipoproteins in plasma.

PMID- 16609146
TI  - Molecular packing and intermolecular interactions in two structural polymorphs of
      N-palmitoylethanolamine, a type 2 cannabinoid receptor agonist.
AB  - The molecular structure, packing properties, and intermolecular interactions of
      two structural polymorphs of N-palmitoylethanolamine (NPEA) have been determined
      by single-crystal X-ray diffraction. Polymorphs alpha and beta crystallized in
      monoclinic space group P2(1)/c and orthorhombic space group Pbca, respectively.
      In both polymorphs, NPEA molecules are organized in a tail-to-tail manner,
      resembling a bilayer membrane. Although the molecular packing in polymorph alpha
      is similar to that in N-myristoylethanolamine and N-stearoylethanolamine,
      polymorph beta is a new form. The acyl chains in both polymorphs are tilted by
      approximately 35 degrees with respect to the bilayer normal, with their
      hydrocarbon moieties packed in an orthorhombic subcell. In both structures, the
      hydroxy group of NPEA forms two hydrogen bonds with the hydroxy groups of
      molecules in the opposite leaflet, resulting in extended, zig-zag type H-bonded
      networks along the b-axis in polymorph alpha and along the a-axis in polymorph
      beta. Additionally, the amide N-H and carbonyl groups of adjacent molecules are
      involved in N-H...O hydrogen bonds that connect adjacent molecules along the b
      axis and a-axis, respectively, in alpha and beta. Whereas in polymorph alpha the
      L-shaped NPEA molecules in opposite layers are arranged to yield a Z-like
      organization, in polymorph beta one of the two NPEA molecules is rotated 180
      degrees , leading to a W-like arrangement. Lattice energy calculations indicate
      that polymorph alpha is more stable than polymorph beta by approximately 2.65
      kcal/mol.

PMID- 16609147
TI  - Quantitative imaging of basic functions in renal (patho)physiology.
AB  - Multiphoton fluorescence microscopy offers the advantages of deep optical
      sectioning of living tissue with minimal phototoxicity and high optical
      resolution. More importantly, dynamic processes and multiple functions of an
      intact organ can be visualized in real time using noninvasive methods, and
      quantified. These studies aimed to extend existing methods of multiphoton
      fluorescence imaging to directly observe and quantify basic physiological
      parameters of the kidney including glomerular filtration rate (GFR) and
      permeability, blood flow, urinary concentration/dilution, renin content and
      release, as well as more integrated and complex functions like the
      tubuloglomerular feedback (TGF)-mediated oscillations in glomerular filtration
      and tubular flow. Streptozotocin-induced diabetes significantly increased single
      nephron GFR (SNGFR) from 32.4 +/- 0.4 to 59.5 +/- 2.5 nl/min and glomerular
      permeability to a 70-kDa fluorophore approximately eightfold. The loop diuretic
      furosemide 2-fold diluted and increased approximately 10-fold the volume of
      distal tubular fluid, while also causing the release of 20% of juxtaglomerular
      renin content. Significantly higher speeds of individual red blood cells were
      measured in intraglomerular capillaries (16.7 +/- 0.4 mm/s) compared with
      peritubular vessels (4.7 +/- 0.2 mm/s). Regular periods of glomerular contraction
      relaxation were observed, resulting in oscillations of filtration and tubular
      flow rate. Oscillations in proximal and distal tubular flow showed similar cycle
      times ( approximately 45 s) to glomerular filtration, with a delay of
      approximately 5-10 and 25-30 s, respectively. These innovative technologies
      provide the most complex, immediate, and dynamic portrayal of renal function,
      clearly depicting the components and mechanisms involved in normal physiology and
      pathophysiology.

PMID- 16609148
TI  - Galphaq-dependent signaling cascades stimulate water-seeking behavior.
AB  - We used the mouse nephrin promoter to express a constitutively active Galphaq
      [Galphaq(Q>L)] transgene in mice. As previously reported, the transgene was
      expressed in kidney, pancreas, and brain, and the kidney phenotype was
      characterized by albuminuria and reduced nephron mass. Additional studies
      revealed a second phenotype characterized by polyuria and polydipsia. The
      polyuric phenotype was not caused by abnormal glucose metabolism or hypercalcemia
      but was accompanied by reduced urinary concentrating ability. Additional studies
      found that 1) water restriction was associated with an appropriate increase in
      serum vasopressin levels in transgenic (TG) mice; 2) the urinary concentrating
      defect was not corrected by administration of desamino-d-arginine vasopressin
      (DDAVP); and 3) papillary length was similar in TG and non-TG mice. To examine
      the renal response to DDAVP at the molecular level, we monitored aquaporin 2
      (AQP2) and vasopressin V2 receptor (V2R) mRNA levels in mouse kidney. Consistent
      with the known effects of vasopressin, administration of DDAVP caused a decrease
      in V2R mRNA levels and an increase in AQP2 mRNA levels in both TG and non-TG
      animals, suggesting an appropriate renal response to DDAVP in the TG mice. To
      determine whether the urine concentrating abnormality was the result of primary
      polydipsia, water intake by TG mice was restricted to the amount ingested by non
      TG animals. After 5 days, urinary concentrating ability was similar in TG mice
      and non-TG littermate controls. These data are consistent with the notion that
      expression of the Galphaq(Q>L) transgene in the brain induced primary polydipsia
      in the TG mice.

PMID- 16609149
TI  - Pioglitazone mitigates renal glomerular vascular changes in high-fat, high
      calorie-induced type 2 diabetes mellitus.
AB  - Our hypothesis is that impairment of peroxisome proliferator-activated receptor
      gamma (PPARgamma) initiates renal dysfunction by increasing renal glomerular
      matrix metalloproteinase-2 (MMP-2) activity because of increased renal
      homocysteine (Hcy) and decreased nitric oxide (NO) levels. C57BL/6J mice were
      made diabetic (D) by being fed a high-fat-calorie diet, and an increase in
      PPARgamma activity was induced by adding pioglitazone (Pi) to the diet. Mice were
      grouped as follows: normal calorie diet (N), D, N+Pi, and D+Pi (n = 6/group). The
      glomerular filtration rate (GFR), renal artery blood flow and pressure, and
      plasma glucose were measured. Renal glomeruli and preglomerular arterioles were
      isolated. Plasma and glomerular levels of NO, Hcy, and MMP activity were
      measured. The contractile response to phenylephrine and the dilatation response
      to acetylcholine in renal arteriolar rings were measured in a tissue myobath. In
      N, D, N+Pi, and D+Pi groups, respectively, GFR was 9.4 +/- 1.2, 3.9 +/- 1.1, 9.2
      +/- 1.6, and 8.4 +/- 1.4 microl x min(-1) x g body wt(-1). Renovascular
      resistance was 140 +/- 3, 367 +/- 21, 161 +/- 9, and 153 +/- 10 mmHg x ml x min(
      1). Levels of Hcy were increased from 5.8 +/- 1.5 in the N to 18.0 +/- 4.0
      micromol/l in the D group. Glomerular levels of MMP-2 were increased in D mice
      compared with N mice, and there was no change in levels of MMP-9. Treatment with
      Pi ameliorated glomerular levels of MMP-2 and Hcy in the D group. Renal artery
      ring contraction and relaxation by phenylephrine and acetylcholine, respectively,
      were attenuated in the D groups compared with the N groups. Results suggest that
      a PPARgamma agonist ameliorates preglomerular arteriole remodeling in diabetes by
      decreasing tissue levels of Hcy and MMP-2 activity and increasing NO.

PMID- 16609150
TI  - More than colocalizing with polycystin-1, polycystin-L is in the centrosome.
AB  - Polycystin-1 and polycystin-2 are involved in autosomal dominant polycystic
      kidney disease by unknown mechanisms. These two proteins are located in primary
      cilia where they mediate mechanosensation, suggesting a link between cilia
      function and renal disease. In this study, we sought to characterize the
      subcellular localization of polycystin-L, a closely related member of polycystin
      2, in epithelial renal cell lines. We have shown that endogenous polycystin-l
      subcellular distribution is different in proliferative and nonproliferative
      cultures. Polycystin-L is found mostly in the endoplasmic reticulum in
      subconfluent cell cultures, while in confluent cells it is redistributed to sites
      of cell-cell contact and to the primary cilium as is polycystin-1. Subcellular
      fractionation confirmed a common distribution of polycystin-L and polycystin-1 in
      the fractions corresponding to those containing the plasma membrane of
      postconfluent cells. Reciprocal coimmunoprecipitation experiments showed that
      polycystin-L was associated with polycystin-1 in a common complex in both
      subconfluent and confluent cell cultures. Interestingly, we also identified a
      novel site for a polycystin member (polycystin-L) in unciliated cells, the
      centrosome, which allowed us to reveal an involvement of polycystin-l in cell
      proliferation.

PMID- 16609151
TI  - Sex differences in heat shock protein 72 expression and localization in rats
      following renal ischemia-reperfusion injury.
AB  - Previously, we demonstrated gender differences in Na-K-ATPase (NKA) expression
      and function after renal ischemia-reperfusion (I/R) injury (Sex differences in
      the alterations of Na(+), K(+)-ATPase following ischemia-reperfusion injury in
      the rat kidney. J Physiol 555: 471-480, 2004). Postischemic membrane destruction
      causes inhibition of NKA, whereas heat shock protein (HSP) 72 helps to preserve
      it. We tested the sex differences in postischemic expression of HSP72 and
      colocalization with NKA. The left renal pedicle of uninephrectomized female (F)
      and male (M) Wistar rats was clamped for 55 min followed by 2 (T2), 16 (T16), and
      24 h (T24) of reperfusion. Uninephrectomized, sham-operated F and M rats served
      as controls. Postischemic blood urea nitrogen (BUN), serum creatinine, and renal
      histology were analyzed. HSP72 mRNA expression was detected by RT-PCR, protein
      levels by Western blot analysis. Fluorescent immunohistochemistry was performed
      to evaluate the localization of HSP72 and NKA alpha(1)-subunit. Postischemic BUN
      and creatinine were higher, and renal histology showed more rapid progression in
      M vs. F (P < 0.05). HSP72 mRNA expression was higher in F vs. M in control and in
      all I/R groups (P < 0.05). Similar changes were observed in HSP72 protein levels
      (F vs. M, P < 0.05, control, T2, T16, T24, respectively). Immunohistochemical
      localization of HSP72 and NKA alpha(1) was similar in control F and M. In
      postischemic F kidneys, the majority of NKA alpha(1) and HSP72 was colocalized on
      the basolateral membrane of tubular cells, whereas in M prominent staining was
      observed in the cytosol and apical domain. This study indicates that in female
      kidneys the higher basal and postischemic levels of HSP72 and different
      colocalization with NKA might contribute to the gender differences in renal I/R
      injury.

PMID- 16609152
TI  - Altered phenotype of cultured urothelial and other stratified epithelial cells:
      implications for wound healing.
AB  - The differentiation of cultured stratified epithelial cells can deviate
      significantly from that of normal epithelium, leading to suggestions that
      cultured cells undergo abnormal differentiation, or a truncated differentiation.
      Thus cultured epidermal and corneal epithelial cells stop synthesizing their
      tissue-specific keratin pair K1/K10 and K3/K12, respectively. The replacement of
      these keratins in the suprabasal compartment by K6/K16 keratins that are made by
      all stratified squamous epithelia during hyperplasia rules out a truncated
      differentiation. Importantly, the keratin pattern of in vivo corneal epithelium
      undergoing wound repair mimics that of cultured rabbit corneal epithelial cells.
      Although cultured urothelial cells continue to synthesize uroplakins, which
      normally form two-dimensional crystalline urothelial plaques covering almost the
      entire apical urothelial surface, these proteins do not assemble into crystals in
      cultured cells. Cultured epithelial cells can, however, rapidly regain normal
      differentiation on the removal of mitogenic stimuli, the use of a suitable
      extracellular matrix, or the transplantation of the cells to an in vivo,
      nonmitogenic environment. These data suggest that cultured epithelial cells adopt
      altered differentiation patterns mimicking in vivo regenerating or hyperplastic
      epithelia. Blocking the synthesis of tissue-specific differentiation products,
      such as the K1 and K10 keratins designed to form extensive disulfide cross-links
      in cornified cells, or the assembly of uroplakin plaques allows epithelial cells
      to better migrate and proliferate, activities that are of overriding importance
      during wound repair. Cultured urothelial and other stratified epithelial cells
      provide excellent models for studying the regulation of the synthesis and
      assembly of differentiation products, a key cellular process during epithelial
      wound repair.

PMID- 16609153
TI  - Effect of low environmental salinity on plasma composition and renal function of
      the Atlantic stingray, a euryhaline elasmobranch.
AB  - Marine elasmobranchs maintain internal osmolality higher than their external
      environment, resulting in an osmotic gradient for branchial water uptake. This
      gradient is markedly increased in low-salinity habitats. The subsequent increase
      in water uptake presents a challenge to volume homeostasis. The Atlantic stingray
      is a marine elasmobranch that inhabits a remarkable range of environmental
      salinities. We hypothesized that the ability of these stingrays to regulate fluid
      volume in low-salinity environments is due primarily to a renal glomerular and
      tubular functional reserve. We tested this hypothesis by measuring renal
      excretory function after a rapid and sustained 50% reduction in the osmolality of
      the external medium. Atlantic stingrays were maintained in harbor water [control
      salinity (CS) approximately 850 mosmol/kgH(2)O] for 1 wk. Rays were then either
      transferred to diluted harbor water [low salinity (LS) approximately 440
      mosmol/kgH(2)O] or maintained in CS for a further 24 h. Renal excretory function
      was markedly higher in the rays subjected to low salinity. Glomerular filtration
      rate was threefold higher and urine flow rate ninefold higher in the LS group.
      The clearance of solute-free water was greater, and solute-free water comprised a
      significantly larger proportion of the urine output for the stingrays transferred
      to dilute harbor water. We conclude that 1) the kidneys of Atlantic stingrays
      have a remarkable glomerular and tubular functional reserve, and 2) the marked
      increase in renal function attenuates the increase in fluid volume when these
      fish move into low-salinity habitats.

PMID- 16609154
TI  - Hepatitis C: changing genotype distribution with important implications for
      patient management.
AB  - In The Netherlands an estimated 0.1 to 0.4% of the population are chronic
      hepatitis C (HCV) carriers (15,000 to 60,000 persons). HCV is characterised by
      genetic heterogeneity and six different genotypes have been identified. The
      distribution of HCV genotypes is relevant for the clinician, since there are
      important genotype-specific differences in response to interferon-alpha based
      treatment regimens. Between 1993 and 2005 a shift was observed in The Netherlands
      from a dominant prevalence of genotype 1 to a situation in which genotype non-1
      is becoming more important.

PMID- 16609155
TI  - A major leap in the diagnosis of pulmonary embolism.

PMID- 16609156
TI  - Fc gamma receptor mediated modulation of dendritic cells as a potential strategy
      in the battle against rheumatoid arthritis.
AB  - Autoimmune diseases such as rheumatoid arthritis (RA) result from a deregulation
      of immune responses culminating in immune-mediated tissue injury. In RA, this
      tissue injury is mainly reflected by synovitis and subsequent joint damage,
      although involvement of visceral organs (heart, lungs and kidneys) often leads to
      severe comorbidity. Accumulating evidence points towards dendritic cells (DC) as
      the principal regulators of the balance between immunity and tolerance. Recently,
      a large body of evidence has demonstrated that the balance between activating and
      inhibitory Fc gamma receptor (Fc gammaR) subtypes is intricately involved in the
      regulation of DC behaviour. In this overview we summarise recent findings from
      our group and others that suggest an important role for Fc gammaR in arthritis.
      Furthermore, we postulate novel mechanisms of how triggering of Fc gammaR might
      be used to manipulate DC function and combat autoimmunity. When DC are envisaged
      as useful targets in the light of DC immunotherapy in RA, detailed knowledge on
      the regulatory pathways of Fc gammaR in RA is of paramount importance.

PMID- 16609157
TI  - Genotype distribution amongst hepatitis C patients in The Netherlands.
AB  - BACKGROUND: The prevalence of the genotypes of the hepatitis C virus (HCV)
      differs according to geographical location. In the United States and in European
      countries, the majority of patients are infected with genotype 1, 2 or 3. There
      is a lack of data on the distribution of HCV genotypes in The Netherlands.
      METHODS: The current survey determined the distribution of HCV genotypes amongst
      recently genotyped patients seen by physicians treating hepatitis C in The
      Netherlands. RESULTS: Almost half of the 351 patients (49.3%) were infected with
      genotype 1. Genotype 3 was the second most dominant genotype with a prevalence of
      29.3%. Genotypes 2 and 4 were found in 9.7 and 10.5% of the patients,
      respectively. For 61.5% of the patients (n=216), the subtype was available. For
      genotype 1 the prevalence of subtype 1a and 1b was very similar, while for
      genotype 3 a large majority of patients were infected with subtype 3a.
      CONCLUSION: This survey gives the first estimation of the distribution of HCV
      genotypes amongst unselected HCV patients in The Netherlands.

PMID- 16609158
TI  - Prevalence and clinical characteristics of insulin-treated, anti-GAD-positive,
      type 2 diabetic subjects in an outpatient clinical department of a Dutch teaching
      hospital.
AB  - BACKGROUND: In clinical practice, type 1 and type 2 diabetic patients are
      sometimes difficult to distinguish. Type 1 diabetes has an immune-mediated
      pathogenesis, resulting in a loss of insulin-secreting beta-cells. Type 2
      diabetes mellitus is characterised by a relative insulin insufficiency, without
      the presence of an autoimmune aetiology, initially due to insulin resistance and
      later also accompanied by defective insulin release. Latent autoimmune diabetes
      of the adult (LADA) is a subgroup of diabetes, somewhere on the borderland
      between type 1 and type 2 diabetes. LADA is characterised by a late-age onset and
      relatively mild progression, but with unmistakable signs of autoimmunity, such as
      the presence of the autoimmune antibodies anti-GAD65, anti-insulin antibodies, or
      anti-Ia-2ab. OBJECTIVE: To establish the prevalence of anti-GAD ina diabetic
      outpatient clinic of a Dutch, non-university,teaching hospital and to describe
      these patients clinical and laboratory features, especially of the metabolic
      syndrome. METHODS: We evaluated GAD65 antibodies and other parameters in 244
      selected diabetic patients, who had been on oral therapy for at least three
      months before becoming insulin-dependent. RESULTS: Twenty-six patients (11.6%)
      were positive for GAD65 antibodies. These patients had a significantly lower BMI
      (27.8 +/- 4.5 vs 31.1 +/- 4.9; p<0.01); less often cerebrovascular accidents
      (19.2 vs 34.9%; p<0.01) and a higher HDL cholesterol (1.73 +/- 0.53 vs 1.21 +/-
      0.38; p<0.05). In contrast, anti-GAD patients had a significantly higher
      prevalence of hypothyroidism (23.0 vs 6.6%; p<0.05). CONCLUSION: Anti-GAD
      positive patients represent a sizable proportion of type 2 diabetes in a second
      line outpatient clinic, and they are characterised by lower parameters of the
      metabolic syndrome, but higher prevalence of other autoimmune phenomena such as
      hypothyroidism.

PMID- 16609159
TI  - Fibrillary glomerulonephritis in a patient with type 2 diabetes mellitus.
AB  - We report a 62-year-old man with documented type 2 diabetes mellitus and
      hypertension, who presented with a rapid deterioration in renal function. The
      sudden decrease in renal function in this well-controlled diabetic patient
      prompted us to consider a nondiabetic and nonhypertensive cause. The urinary
      sediment showed a glomerular haematuria suggestive of glomerulonephritis. A
      diagnosis of fibrillary glomerulonephritis was made on renal biopsy. Fibrillary
      glomerulonephritis is a rarely diagnosed disease with clinical manifestations
      such as proteinuria, microscopic haematuria, nephrotic syndrome and impairment of
      renal function. A diagnosis of fibrillary glomerulonephritis can only be made by
      electronmicroscopy of the renal tissue. In this case report the spectrum of this
      disease is reviewed.

PMID- 16609160
TI  - Azathioprine-induced shock in a patient suffering from undifferentiated erosive
      oligoarthritis.
AB  - Shock due to a hypersensitivity response to azathioprine is unpredictable, occurs
      seldom and bears a potentially fatal outcome. Azathioprine is widely used in the
      treatment of autoimmune diseases and in solid organ transplantation. Here, we
      present a patient who suffered from undifferentiated erosive oligoarthritis and
      was treated with azathioprine. This patient developed anaphylactic shock which
      was interpreted as a side effect of azathioprine. Although rare, similar cases
      were described since 1980.

PMID- 16609161
TI  - Successful treatment of liposomal amphotericin B refractory Candida glabrata
      fungaemia in a patient undergoing a stem cell transplantation.
AB  - Blood stream infections caused by Candida glabrata are difficult to manage. We
      describe a patient who underwent an allogeneic peripheral stem cell
      transplantation for acute myeloid leukaemia. The patient developed C. glabrata
      fungaemia that was refractory to liposomal amphotericin B therapy. After changing
      the therapy to caspofungin, blood cultures became sterile within two days and the
      patient recovered clinically. The patient died shortly after due to graft-versus
      host disease and at autopsy there was no evidence of residual or persistent
      Candida infection. Caspofungin was effective in liposomal amphotericin-B
      refractory C. glabrata fungaemia and proved to rapidly clear the infection.
      Treatment options for candidaemia are discussed.

PMID- 16609162
TI  - A patient with swollen ears and ECG abnormalities.

PMID- 16609163
TI  - Helicobacter pylori, obesity and gastro-oesophageal reflux disease: is there a
      relation?

PMID- 16609164
TI  - A new high-speed beam chopper for time-resolved X-ray studies.
AB  - A new high-speed X-ray beam chopper, which can be phase locked to the temporal
      structure of the Advanced Photon Source (APS) storage ring, has been developed
      and tested. The open window time of the chopper is 2450 ns, which corresponds to
      approximately 67% of the revolution time of the APS storage ring. By phase
      locking the rotation of the beam chopper to the storage-ring orbital frequency,
      any portion of the storage-ring fill pattern can be positioned within the beam
      chopper transmission-time window.

PMID- 16609165
TI  - SB7: the new bending-magnet double-headed dragon beamline at SuperACO.
AB  - A new beamline is now operational at LURE on bending-magnet 7 of the SuperACO
      storage ring in Orsay. The monochromator is of the ;dragon' type, designed to
      work in the energy range 150-1500 eV, and is equipped with a double vertical
      focusing mirror in order to allow for fast switching of light polarization. In
      this paper the results of photoion-yield experiments performed on N(2), Ar and Ne
      gases are presented. The observed resonance structures enable us to determine the
      available energy resolution: a resolving power higher than 8500 is obtained at
      the Ar 2p, N 1s and Ne K-edges when using all the optical elements at full
      aperture. The total flux as a function of the measured photon energy resolution
      and the characterization of the double-head behaviour in delivering circularly
      polarized light are reported.

PMID- 16609166
TI  - Performance limits of direct cryogenically cooled silicon monochromators -
      experimental results at the APS.
AB  - The successful use of cryogenically cooled silicon monochromators at third
      generation synchrotron facilities is well documented. At the Advanced Photon
      Source (APS) it has been shown that, at 100 mA operation with the standard APS
      undulator A, the cryogenically cooled silicon monochromator performs very well
      with minimal (<2 arcsec) or no observable thermal distortions. However, to date
      there has not been any systematic experimental study on the performance limits of
      this approach. This paper presents experimental results on the performance limits
      of these directly cooled crystals. The results show that if the beam is limited
      to the size of the radiation central cone then, at the APS, the crystal will
      still perform well at twice the present 100 mA single 2.4 m-long 3.3 cm-period
      undulator heat load. However, the performance would degrade rapidly if a much
      larger incident white-beam size is utilized.

PMID- 16609167
TI  - Rapid methods for the calibration of solid-state detectors.
AB  - A complementary pair of rapid methods for the energy calibration of solid-state
      detectors have been developed. Each method requires only a single measurement
      from either (i) a glass sample containing elements chosen to produce fluorescence
      lines over a suitable energy range when exposed to a polychromatic beam of X
      rays, or (ii) a powder diffraction standard in the presence of diffraction slits.
      The fluorescent glass method has the advantage of allowing simultaneous energy
      calibration of a number of detectors without requiring diffraction slits. There
      is the potential for the glass material to be incorporated into virtually any
      sample holder to allow a continuous in situ calibration. Complementary
      observations of a powder diffraction standard allow simultaneous calibration of
      diffraction 2theta and monitoring of the detector for drift.

PMID- 16609168
TI  - Deconvoluting ultrafast structural dynamics: temporal resolution beyond the pulse
      length of synchrotron radiation.
AB  - 100 picosecond X-ray snapshots visualizing the structural dynamics of
      macromolecular systems are now routinely available at synchrotron sources. A
      wealth of fundamental processes in photochemistry, condensed matter physics and
      biology, however, occur on considerably faster time scales. Standard experimental
      protocols at synchrotron sources cannot provide structural information with
      faster temporal resolution as these are limited by the duration of the electron
      bunch within the synchrotron ring. By walking the timing of femtosecond laser
      photolysis through a (much longer) X-ray pulse in steps of a few picoseconds,
      structural information on ultrafast dynamics may be retrieved from a set of X-ray
      scattering images, initially through deconvolution and subsequently through
      refinement. This experimental protocol promises immediate improvements in the
      temporal resolution available at synchrotron sources, facilitating the study of a
      number of rapid complex photochemical processes. Combined with techniques which
      reshape the X-ray probe pulse, the accessible temporal domain could further be
      extended to near-picosecond resolution.

PMID- 16609169
TI  - Simultaneous IR and time-resolved X-ray diffraction measurements for studying
      self-sustained reactions.
AB  - Self-propagating high-temperature synthesis provides an attractive practical
      method for producing advanced materials such as ceramics, composites and
      intermetallics. This kind of reaction has been investigated in situ using time
      resolved X-ray diffraction, with an X-ray synchrotron beam (D43 beamline, LURE,
      Orsay) coupled to simultaneous IR thermography to study structural
      transformations and thermal evolution. With short acquisition times (30 ms per
      pattern) it has been possible to observe several steps before obtaining
      compounds. Two different compound formations have been described: (i) the
      different steps of reaction, aluminium melting, subsequent temperature increase
      and fast reaction between Al and Ni at such temperatures that only Ni and AlNi
      are solid and all other compositions are liquid and well identified; (ii) the
      formation of FeAl. Here, a portion of the iron seems to transform into its
      allotropic phase and this transition stabilizes the reaction temperature at
      approximately 1173 K. In addition, the aluminium melting during the reaction
      explains why the nanostructure induced by the mechanical activation is maintained
      in the end product.

PMID- 16609170
TI  - Mapping of a particular element using an absorption edge with an X-ray
      fluorescence imaging microscope.
AB  - An X-ray fluorescence imaging microscope with a Wolter-type objective mirror
      (magnification: 13) has been constructed at beamline 39XU of SPring-8.
      Monochromatic X-rays (DeltaE/E approximately 10(-4)) in the energy range 6-10 keV
      were used for X-ray fluorescence excitation of the specimens. Using two
      monochromatic X-rays above and below the absorption edge of a particular element,
      a two-dimensional image of the element could be obtained. As a result, two
      dimensional element mapping of the test specimens (Cu, Co, Ni, Fe and Ti wires)
      and constituent minerals (Fe, Mn and Ti) of a rock specimen (a piemontite-quartz
      schist) became possible.

PMID- 16609172
TI  - Future structural biology applications with a free-electron laser - more than
      wild dreams?
AB  - A workshop entitled Potential Future Applications in Structural Biology of an X
      ray Free-Electron Laser at DESY was held at Hamburg, Germany, on 4-8 July 1999.
      The aim of the workshop was to identify and discuss potential applications in
      structural biology using the specific beam properties of the planned X-ray free
      electron laser at DESY, Hamburg. The workshop focused on proposals in X-ray
      crystallography, spectroscopy, microscopy and holography. In the discussions
      during the workshop, the response of biological material to the expected high
      photon flux and its time dependence played a central role. Technological aspects
      in data recording and image interpretation were covered as well. There was
      general agreement that an X-ray free-electron laser source with its specific
      source parameters could offer unique opportunities for novel experiments in
      structural biology, complementing current synchrotron facilities. The realization
      of future applications will be challenged by the handling of large high-energy
      doses on the biological specimen and the development of equipment capable to
      respond to a pulse time structure in the femtosecond range.

PMID- 16609174
TI  - The historical development of cryogenically cooled monochromators for third
      generation synchrotron radiation sources.
AB  - In the period of the late-1980s, before the construction of multi-GeV third
      generation storage rings with their intense insertion-device sources, the
      perceived number one problem for X-ray instrumentation was proper cooling of the
      first optical element in the beamline. This article, first given as an acceptance
      speech for the Compton Award ceremony at the Advanced Photon Source, presents a
      somewhat historical and anecdotal overview of how cryogenically cooled
      monochromator optics have been developed to provide a monochromator cooling
      solution adequate for today's power levels. A series of workshops and
      international collaborations were the key components for the progress and final
      success of this development.

PMID- 16609175
TI  - Design of a vacuum-compatible high-precision monochromatic beam-position monitor
      for use with synchrotron radiation from 5 to 25 keV.
AB  - The Structural Biology Center beamline, 19ID, has been designed to take full
      advantage of the highly intense undulator radiation and very low source emittance
      available at the Advanced Photon Source. In order to keep the X-ray beam focused
      onto the pre-sample slits, a novel position-sensitive PIN diode array has been
      developed. The array consists of four PIN diodes positioned upstream of a 0.5
      microm-thick metal foil placed in the X-ray beam. Using conventional difference
      over-the-sum techniques, two-dimensional position information is obtained from
      the metal foil fluorescence. Because the full X-ray beam passes through the metal
      foil, the true beam center-of-mass is measured. The device is compact,
      inexpensive to construct, operates in a vacuum and has a working range of 8 mm x
      10 mm that can be expanded with design modifications. Measured position
      sensitivity is 1-2 microm. Although optimized for use in the 5-25 keV energy
      range, the upper limit can be extended by changing metals or adjusting foil
      thickness.

PMID- 16609176
TI  - Performance of bent-crystal monochromators for high-energy synchrotron radiation.
AB  - Two monochromators for high-energy synchrotron radiation have been studied at the
      elliptical multipole wiggler beamline BL08W of SPring-8. Both monochromator
      crystals are bent and indirectly water-cooled. In the 100 keV monochromator an
      efficient cooling scheme is employed. A monochromatic beam is successfully
      focused using new benders for the 100 keV and 300 keV monochromators. Measured
      radii of curvature of the bent crystal agree qualitatively with calculation.

PMID- 16609177
TI  - Meridional focusing of X-rays diffracted onto a single crystal with a transversal
      groove (Bragg-diffraction asymmetric lens).
AB  - It is shown that a properly designed transversal groove machined into the surface
      of a single-crystal monochromator may concentrate (focus) the diffracted
      radiation meridionally. From this result and from previous papers on the Bragg
      diffraction inclined lens it follows that a properly designed depression
      fabricated into the surface of a single-crystal monochromator should provide two
      dimensional focusing of a diffracted synchrotron radiation beam.

PMID- 16609178
TI  - Parametric down conversion of X-ray photons.
AB  - Parametric down conversion of X-ray photons in diamond crystals was detected in
      two experiments, both using the phase-matching scheme first employed in the X-ray
      regime by Eisenberger & McCall [Phys. Rev. Lett. (1971), 26, 684-688]. The
      conversion events were detected by a combination of time-correlation spectroscopy
      and energy discrimination, using Si drift-chamber detectors. The time-correlation
      spectra give a direct comparison of the conversion rate over the accidental
      coincidence rate. Mechanisms for possible detection of false events and ways to
      cross check against them are discussed in detail.

PMID- 16609179
TI  - Rapid and sensitive XAFS using a tunable X-ray undulator at BL10XU of SPring-8.
AB  - The design and performance of the high-brilliance XAFS facility at BL10XU of
      SPring-8, aimed at rapid and sensitive measurement of X-ray absorption fine
      structure (XAFS), is reported. Both undulator gap and double-crystal
      monochromator have been successfully controlled covering a wide energy range (5
      30 keV). A versatile goniometer system, consisting of two independent high
      precision goniometers, is capable of polarized XAFS in fluorescence mode and
      surface-sensitive experiments using a grazing-incidence geometry. By sharing
      major components, i.e. a monolithic Ge 100-pixel array detector and a closed
      cycle He cryostat, both polarized XAFS and X-ray standing wave (XSW) experiments
      can be performed at low temperature (15-300 K). The performance of the
      spectrometer has been evaluated by recording XAFS spectra in transmission mode.

PMID- 16609180
TI  - Path-integral approach to Debye-Waller factors in EXAFS, EELS and XPD for cubic
      and quartic anharmonic potentials.
AB  - In this paper thermal effects in extended X-ray absorption fine structure (EXAFS)
      and X-ray photoelectron diffraction (XPD) due to atomic vibration in cubic and
      quartic potentials are studied by use of Feynman's path-integral approach. This
      approach can be applied to strongly anharmonic systems where the cumulant
      analyses break down. It is closely related to the well known classical approach
      which is only valid at high temperature. The phase of the thermal factor plays an
      important role both in EXAFS and XPD analyses for the asymmetric potential with
      strong anharmonicity. At low temperature the cumulant expansion up to the second
      order for the thermal damping function agrees well with the self-consistent
      result, but up to higher orders should be taken into account for the phase
      function. At high temperature the result from self-consistent calculations shows
      the characteristic behaviour: the thermal damping function is negative in the
      high-k region for both strongly and weakly anharmonic systems. The cumulant
      approximation cannot reproduce this behaviour. For the strongly anharmonic
      systems the quantum result shows qualitatively different behaviour from the
      classical approximation at low temperature: the former does not show the negative
      values even in the high-k region, while the latter shows the phase inversion in
      the amplitude.

PMID- 16609181
TI  - A conical slit for three-dimensional XRD mapping.
AB  - Traditionally, depth resolution in diffraction experiments is obtained by
      inserting pinholes in both the incoming and diffracted beam. For materials
      science investigations of local strain and texture properties this leads to very
      slow data-acquisition rates, especially when characterization is performed on the
      level of the individual grains. To circumvent this problem a conical slit has
      been manufactured by wire-electrodischarge machining. The conical slit has six 25
      microm-thick conically shaped openings matching six of the Debye-Scherrer cones
      from a face-centred-cubic powder. By combining the slit with a microfocused
      incoming beam of hard X-rays, an embedded gauge volume is defined. Using a two
      dimensional detector, fast and complete information can be obtained regarding the
      texture and strain properties of the material within this particular gauge
      volume. The average machining and assemblage errors of the conical slit are found
      both to be of the order of 5 microm. An algorithm for alignment of the slit is
      established, and the potential of the technique is illustrated with an example of
      grain mapping in a 4.5 mm-thick Cu sample.

PMID- 16609182
TI  - A specimen chamber for soft X-ray spectromicroscopy on aqueous and liquid
      samples.
AB  - A specimen chamber is described for soft X-ray spectromicroscopy of hydrated
      specimens and solutions. Applications include imaging and carbon edge
      spectroscopy of hydrated clay/polymer suspensions.

PMID- 16609183
TI  - SR source to science.

PMID- 16609184
TI  - Fourth-generation X-ray sources: some possible applications to biology.
AB  - The term 'fourth generation X-ray sources' has come to mean X-ray free-electron
      lasers which use multi-GeV electron beams from linear accelerators to generate X
      rays by self-amplified stimulated emission when fired into long undulators.
      Properties of the radiation expected from such sources are reviewed briefly and
      two possible applications of the resulting pulsed highly collimated X-radiation
      to problems in biology are discussed: use of X-ray photon correlation
      spectroscopy to measure time correlations of atoms in protein crystals, and use
      of Mossbauer radiation extracted from the photon beams by resonant Bragg
      diffraction from (57)Fe-containing crystals, for MAD phasing of very large unit
      cell biomolecular crystals and possibly for photon echo measurements.

PMID- 16609185
TI  - Recent trends of insertion-device technology for X-ray sources.
AB  - As a consequence of the developments of in-vacuum undulators, where permanent
      magnet arrays are located in an ultrahigh vacuum, the in-vacuum mini-gap
      undulator with very short period has been successful in the X-ray ring of NSLS in
      collaboration with SPring-8, producing a new concept for synchrotron radiation
      facilities. The key feature of the concept is the combination of in-vacuum mini
      gap undulators and a low-emittance ring with moderate beam energy. In other words
      there are possibilities for the design of a moderate-cost medium-sized
      synchrotron radiation facility, the performance of which may be comparable with
      that of the existing large-scale facilities. Here the performance of in-vacuum
      undulators is described, particularly of the mini-gap type. Also described is the
      essence of the new concept for synchrotron radiation facilities, the so-called
      new third-generation light source.

PMID- 16609186
TI  - Feasibility and review of anomalous X-ray diffraction at long wavelengths in
      materials research and protein crystallography.
AB  - The feasibility and a review of progress in the long-wavelengths anomalous
      dispersion technique is given in the context of the development of beamline ID1
      of the ESRF for such studies. First experiments on this beamline and their
      analyses are described. The first study reports on the use of uranium which
      exhibits an unusually strong anomalous dispersion at its M(V) absorption edge
      (lambda(M(V)) = 3.5 A). The anomalous scattering amplitude of uranium with 110
      anomalous electrons exceeds the resonance scattering of other strong anomalous
      scatterers like that of the rare earth ions by a factor of four. The resulting
      exceptional phasing power of uranium is most attractive in protein
      crystallography using the MAD method. The anomalous dispersion of a uranium
      derivative of asparaginyl-tRNA synthetase (hexagonal, a = 124.4 A, c = 123.4 A)
      has been measured at three wavelengths near the M(V) edge using beamline ID1 of
      the ESRF. The present set-up allowed the measurement of 10% of the possible
      reflections at a resolution of 8 A. This is mainly due to the low sensitivity of
      the CCD camera. The second study, involving DAFS experiments at wavelengths near
      the K-absorption edge of chlorine (lambda(K) = 4.4 A), reports the use of salt
      crystals which give rise to much stronger intensities of diffraction peaks than
      those of protein crystals. In the case of a crystal of pentamethylammonium
      undecachlorodibismuthate (PMACB, orthorhombic, a = 13.00 A, b = 14.038 A, c =
      15.45 A), all reflections within the resolution range from 6.4 A to 3.5 A and the
      total scan width of 24 degrees were collected. The crystalline structure of PMACB
      implies two chemically distinct states of the Cl atom. Consequently, different
      dispersions near the K-edge of chlorine are expected. The dispersion of the
      intensity of five Bragg peaks of the PMACB crystal has been measured at 30
      wavelengths. The relative success of these preliminary experiments with X-rays of
      long wavelength shows that the measurement of anomalous X-ray diffraction at
      wavelengths beyond 3 A is feasible. Starting from the experience gained in these
      experiments, an increased efficiency of the instrument ID1 by two to three orders
      of magnitude will be achieved in this wavelength range. A comparison with
      different techniques of anomalous diffraction which rely on the use of
      argon/ethane-filled multiwire chambers and image plates as detectors for
      wavelengths near the K-edge of sulfur and phosphorus is also given.

PMID- 16609187
TI  - Anomalous scattering for small-molecule crystallography.
AB  - Anomalous dispersion techniques in small-molecule crystallography have been used
      in recent years with the advent of intense tunable X-radiation from synchrotron X
      ray sources. By tuning the wavelength of the radiation close to the absorption
      edges of specific elements, it is possible to identify and distinguish between
      atoms which are close together in atomic number, even when two or more such atoms
      occupy a single site. Anomalous dispersion techniques can also be used to
      distinguish between valence states of different sites of an element by the
      valence contrast method or to determine the coordination geometry of an atom. In
      some cases, when the coordination of an atom is asymmetric, the absorption-edge
      position may depend on the orientation of the crystal. Finally, anomalous
      dispersion techniques can be used for ab initio structure solution from powder
      diffraction data. The properties of microporous materials often depend on the
      incorporation of metal atoms into the framework. Two or more metal atoms close
      together in atomic number may be incorporated, sometimes occupying a single site.
      In one study the site of an Ni atom in the aluminophosphate NiAPO was determined
      by anomalous dispersion techniques and data from the NSLS. Also, the location of
      the isomorphously substituted cobalt over two crystallographically different zinc
      sites was determined in the zincophosphate CoZnPO-CZP, in a five-wavelength study
      using data from ELETTRA.

PMID- 16609188
TI  - Direct phasing of one-wavelength anomalous-scattering data.
AB  - This paper presents a brief survey of methods in ab initio phasing of one
      wavelength anomalous-scattering data. In particular, the method implemented in
      the computer program OASIS has been tested using two new data sets from orotidine
      5'-monophosphate decarboxylase (OMPDC) [Appleby et al. (2000). Proc. Natl Acad.
      Sci. USA. In the press] and PurE [Mathews et al. (1999). Structure, 7(11), 1395
      1406]. The Se atoms were located by the small-molecule program SAPI. The electron
      density maps after OASIS and density modification for both structures clearly
      revealed the Calpha trace and, in the case of PurE, most side-chains. The test
      with the OMPDC data demonstrated that, by exploiting the anomalous signal at a
      single wavelength, direct methods can be used to determine phases at moderate (
      approximately 2.5 A) macromolecular crystallographic resolution for a large-size
      protein (5663 non-H atoms in the asymmetric unit). The exceptionally good quality
      of the electron map shown in the case of PurE suggested that fully automatic
      model fitting is possible.

PMID- 16609189
TI  - Anomalous X-ray scattering for determining the partial structural functions of
      binary liquids.
AB  - The availability of intense white X-rays from synchrotron radiation sources has
      greatly improved both acquisition and quality of anomalous X-ray scattering (AXS)
      measurements. A demonstration is given of the usefulness of the AXS method for
      determining three partial structural functions of liquid matter by some selected
      examples of molten salts such as CuBr and RbBr.

PMID- 16609190
TI  - Charge densities from high-resolution synchrotron X-ray diffraction experiments.
AB  - The combination of intense X-ray sources, especially synchrotron radiation, with
      area-detector technology has accomplished an enormous advance in the experimental
      conditions available for charge-density analysis by single-crystal high
      resolution X-ray diffraction. Such experiments can now be carried out in a time
      measured in hours rather than weeks. Some features of these experiments are
      examined and preliminary results are reported for charge-density studies of 2
      hydroxy-5-nitrobenzaldehyde N-cyclohexylimine (1), octakis(m
      tolylthio)naphthalene (2), and 7-fluoro-4-styrylcoumarin (3). Weak interactions
      in crystals of (1) and (3) are found to have similar charge-density
      characteristics. Cages in the crystal lattice of (2) have a complex charge
      distribution.

PMID- 16609191
TI  - Time- and space-resolved dynamic studies on ceramic and cementitious materials.
AB  - A review is given of the results and lessons arising from a sustained in situ
      diffraction study of the structure and performance of functional
      ceramic/cementitious materials in which synchrotron-based energy-dispersive
      diffraction has been the central under-pinning technique. Five particular points
      of discussion emerge: the demands on time resolution; the use of penetrating
      radiation for the in situ mode; the need for complementary techniques; re
      analysing of data; spatially resolved diffraction: a new tomography. These
      aspects are discussed in turn using illustrative examples taken from the fields
      of cement hydration, clay intercalation, cation-exchanged zeolites, and
      particulate/fluid invasion into building and archaeological objects.

PMID- 16609192
TI  - Magnetization profile of ultrathin FePd films.
AB  - The method of circular dichroism in X-ray resonant magnetic scattering is
      presented which allows a straightforward determination of the magnetization
      profile of magnetic patterns in ultrathin films. Application to single
      crystalline FePd layers shows unambiguously the presence of magnetic flux closure
      domains whose thickness can constitute a significant fraction ( approximately
      25%) of the total film.

PMID- 16609193
TI  - X-ray natural circular dichroism and chiral-EXAFS in gyrotropic crystals.
AB  - X-ray natural circular dichroism (XNCD) has been recently detected in the XANES
      region for uniaxial and biaxial gyrotropic crystals. Chiral-EXAFS (chi-EXAFS)
      spectra are reported for the first time over a wider energy range and are
      analysed in terms of multiple-scattering paths of relevant symmetry. For such
      heavily absorbing single crystals as lithium iodate, paratellurite or potassium
      titanyl phosphate, the differential absorption between left-handed and right
      handed circularly polarized X-ray photons cannot be measured in transmission but
      gyrotropy effects can still be detected in fluorescence excitation spectra.
      Whereas XNCD and fluorescence-detected X-ray natural circular dichroism spectra
      are strictly identical for uniaxial crystals, it has been established that this
      was true only to the first order for biaxial crystals such as potassium titanyl
      phosphate.

PMID- 16609194
TI  - Precision wavelength measurement of the 14.4 keV Mossbauer photon.
AB  - The wavelength of the 14.4 keV Mossbauer photon has been determined by using
      undulator radiation and diffraction of FZ silicon crystals. For the wavelength
      determination a goniometer equipped with a laser rotary encoder and a sine-bar
      angle optical interferometer was developed; a temperature-monitoring system and X
      ray optics related to the experiment were also developed. The mean wavelength was
      0.08602557 nm with an uncertainty of 0.6 p.p.m., derived from 16 measurements of
      three pieces of FZ Si(840) crystals.

PMID- 16609195
TI  - Phase imaging using highly coherent X-rays: radiography, tomography, diffraction
      topography.
AB  - Several hard X-rays imaging techniques greatly benefit from the coherence of the
      beams delivered by the modern synchrotron radiation sources. This is illustrated
      with examples recorded on the 'long' (145 m) ID19 'imaging' beamline of the ESRF.
      Phase imaging is directly related to the small angular size of the source as seen
      from one point of the sample ('effective divergence' approximately microradians).
      When using the ;propagation' technique, phase radiography and tomography are
      instrumentally very simple. They are often used in the 'edge detection' regime,
      where the jumps of density are clearly observed. The in situ damage assessment of
      micro-heterogeneous materials is one example of the many applications. Recently a
      more quantitative approach has been developed, which provides a three-dimensional
      density mapping of the sample ('holotomography'). The combination of diffraction
      topography and phase-contrast imaging constitutes a powerful tool. The
      observation of holes of discrete sizes in quasicrystals, and the investigation of
      poled ferroelectric materials, result from this combination.

PMID- 16609196
TI  - The crystallography beamline I711 at MAX II.
AB  - A new X-ray crystallographic beamline is operational at the MAX II synchrotron in
      Lund. The beamline has been in regular use since August 1998 and is used both for
      macro- and small molecule diffraction as well as powder diffraction experiments.
      The radiation source is a 1.8 T multipole wiggler. The beam is focused vertically
      by a bendable mirror and horizontally by an asymmetrically cut Si(111)
      monochromator. The wavelength range is 0.8-1.55 A with a measured flux at 1 A of
      more than 10(11) photons s(-1) in 0.3 mm x 0.3 mm at the sample position. The
      station is currently equipped with a Mar345 imaging plate, a Bruker Smart 1000
      area CCD detector and a Huber imaging-plate Guinier camera. An ADSC 210 area CCD
      detector is planned to be installed during 2000.

PMID- 16609197
TI  - Effect of surface roughness on the spatial coherence of X-ray beams from third
      generation synchrotron radiation sources.
AB  - The effect of the surface roughness of optical elements, such as Be windows and
      reflection mirrors, in synchrotron radiation beamlines on the spatial coherence
      of the X-ray beam is investigated systematically by means of digital simulation,
      in which a new model for X-ray reflection from a rough surface is proposed. A
      universal factor is employed to evaluate the spatial coherence quantitatively,
      based on which critical values for surface roughness are reached. The results
      from simulation are consistent with those from experiments.

PMID- 16609198
TI  - A study of the response of Y3Al5O12:Ce phosphor powder screens in the vacuum
      ultraviolet and soft X-ray regions using synchrotron radiation.
AB  - Phosphor screens find application in many fields because of their ability to
      convert incident radiation to wavelengths that are readily measured by modern
      detectors. While the response of such screens in the X-ray region has been widely
      studied, much work still remains to be done regarding their response in the
      vacuum ultraviolet and soft X-ray regions, where the response is predicted to be
      non-linear owing to the presence of elemental absorption edges. Here, an
      experiment using synchrotron radiation to determine the response of thin
      Y(3)Al(5)O(12):Ce (1-21 mg cm(-2)) and Y(2)O(3):Eu (2.64 mg cm(-2)) powder
      phosphor screens in the spectral range 20-900 A (13.8-620 eV) is reported. Also,
      a custom-built camera is described which permits simultaneous collection of the
      forward- and backward-emitted light and that enables measurements to be made at
      various positions across the screens and at several screen/incident beam angles.
      Finally, features in the response spectra are identified, and efficiencies across
      the spectral range indicated for different screen thicknesses and operating modes
      are plotted, before a curve of the intrinsic radiant efficiency of
      Y(3)Al(5)O(12):Ce is produced. The results are discussed in the context of other
      measurements.

PMID- 16609199
TI  - A novel application of silicon microstrip technology for energy-dispersive EXAFS
      studies.
AB  - A prototype X-ray detector for energy-dispersive EXAFS has been developed and
      tested to demonstrate the principle of using silicon microstrip detector
      technology for this application. Testing took place at the UK Synchrotron
      Radiation Source, where the absorption spectra of a 5 microm Ni foil and a 25 mM
      NiCl(2) solution were obtained.

PMID- 16609200
TI  - Instrumentation for photocrystallographic experiments of transient species.
AB  - Instrumentation for stroboscopic time-resolved diffraction studies at low
      temperatures is described. Exciting laser light is delivered to the crystal
      through an optical fiber. During the diffraction experiment, fluorescence from
      the sample is focused onto a fiber optic bundle surrounding the laser-light
      fiber, and monitored by a photodiode. A rotating slotted disk produces a pulsed X
      ray beam with pulse frequencies suitable for the study of molecular excited
      states with lifetimes of 10 micros or longer. Synchronization of the laser-pump/X
      ray-probe pulses is achieved through a trigger signal from a photosensor mounted
      on the rotating disk, or from an X-ray sensitive photodiode inserted in the
      beamstop. For the study of shorter-lived species the time structure of the
      synchrotron beam is to be used. Equations are derived for the maximum and average
      fractional excited-state populations as a function of lifetime, pulse frequency
      and the fraction of molecules being excited by the laser pulse.

PMID- 16609201
TI  - Extraction of accurate structure-factor amplitudes from Laue data: wavelength
      normalization with wiggler and undulator X-ray sources.
AB  - Wavelength normalization is an essential part of processing of Laue X-ray
      diffraction data and is critically important for deriving accurate structure
      factor amplitudes. The results of wavelength normalization for Laue data obtained
      in nanosecond time-resolved experiments at the ID09 beamline at the European
      Synchrotron Radiation Facility, Grenoble, France, are presented. Several wiggler
      and undulator insertion devices with complex spectra were used. The results show
      that even in the most challenging cases, such as wiggler/undulator tandems or
      single-line undulators, accurate wavelength normalization does not require
      unusually redundant Laue data and can be accomplished using typical Laue data
      sets. Single-line undulator spectra derived from Laue data compare well with the
      measured incident X-ray spectra. Successful wavelength normalization of the
      undulator data was also confirmed by the observed signal in nanosecond time
      resolved experiments. Single-line undulators, which are attractive for time
      resolved experiments due to their high peak intensity and low polychromatic
      background, are compared with wigglers, based on data obtained on the same
      crystal.

PMID- 16609202
TI  - Micro-SAXS and force/strain measurements during the tensile deformation of single
      struts of an elastomeric polyurethane foam.
AB  - A microdeformation stage based on a piezoelectric crystal actuator capable of
      measuring the force applied to micrometre-sized polymeric samples is described.
      Laboratory force/strain measurements on a single strut of an elastomeric
      polyurethane foam have been conducted for the first time. The device has also
      been used on the microfocus beamline at the European Synchrotron Radiation
      Facility to collect microbeam small-angle X-ray scattering data simultaneously
      with strain and force measurements during the time-resolved tensile deformation
      of a single strut of elastomeric polyurethane foam.

PMID- 16609203
TI  - Rapid characterization of complex structural phase transitions using powder
      diffraction and an area detector.
AB  - The use of a high-intensity and well collimated X-ray beam from a third
      generation synchrotron source, combined with an area detector with online readout
      capabilities, allows high-quality powder patterns to be obtained with exposure
      times of only a few seconds. Powder measurements of a rare-earth manganate
      perovskite (Nd(0.43)Sr(0.57)MnO(3)) were performed in the temperature range 105
      200 K, and the data were of sufficient quality to be able to extract, via
      Rietveld refinement, accurate values for the lattice constants and atomic
      parameters. The temperature dependence of the Mn-O-Mn bond angles and Mn-O
      distances obtained in this manner illustrate the well known correlation between
      the distortion of the MnO(6) octahedra and the onset of orbital ordering. The
      success of this study, for which only two hours of synchrotron beam time was
      required, indicates the enormous improvements in efficiency and throughput which
      area detectors are bringing to powder diffraction experiments.

PMID- 16609204
TI  - In situ EXAFS, X-ray diffraction and photoluminescence for high-pressure studies.
AB  - A new facility for simultaneous extended X-ray absorption of fine structure
      (EXAFS), X-ray diffraction and photoluminescence measurements under high
      pressures has been developed for use on station 9.3 at the Daresbury Laboratory
      Synchrotron Radiation Source. This high-pressure facility can be used at any
      suitable beamline at a synchrotron source. Full remote operation of the rig
      allows simultaneous collection of optical and structural data while varying the
      pressure. The set-up is very flexible and can be tailored for a particular
      experiment, such as time- or temperature-dependent measurements. A new approach
      to the collection of high-pressure EXAFS data is also presented. The approach
      significantly shortens the experimental times and allows a dramatic increase in
      the quality of EXAFS data collected. It also opens up the possibility for EXAFS
      data collection at any pressure which can be generated using a diamond cell. The
      high quality of data collected is demonstrated with a GaN case study. Particular
      attention will be paid to the use of energy-dispersive EXAFS and quick-scanning
      EXAFS techniques under pressure.

PMID- 16609205
TI  - Propagation of statistical errors across EXAFS extraction and Fourier filtering.
AB  - A statistical model for estimating the error bars on the EXAFS signal is
      developed. The average can be calculated at the beginning of the analysis, with
      the estimation of the error bars made directly on the individual measurements;
      the error bars are then propagated across the EXAFS extraction. Furthermore, this
      model also allows the estimation of the error bars on the Fourier transformation
      of the EXAFS signal, and on the filtered EXAFS spectrum after the inverse Fourier
      transform.

PMID- 16609206
TI  - XAS spectroscopy reveals X-ray-induced photoreduction of free and protein-bound
      B12 cofactors.
AB  - Crystal structures of several proteins with a B(12) cofactor show abnormally long
      axial bonds between the cofactor's Co atom and its ;lower' ligand, which is
      typically a protein-derived imidazole from a histidine residue. X-ray absorption
      spectroscopy (XAS) experiments were carried out with the following cofactor
      derivatives to examine the question of whether the bond elongation might be due
      to an X-ray-induced reduction of the cofactor's cobalt centre: aquocobalamin,
      cyanocobalamin, methylcobalamin, 5'-desoxyadenosylcobalamin and cob(II)alamin.
      Each cofactor was investigated at 100 K in a water/glycerol or water/trehalose
      glass, both as unbound free species and bound to the protein components of the
      enzyme glutamate mutase. XAS data were collected for each sample around the
      cobalt absorption edge before and after exhaustive (10 min) irradiation with X
      rays of energy 7.76 keV. While XAS spectra for cob(II)alamin, methylcobalamin and
      5'-desoxyadenosylcobalamin were the same (within experimental error) before and
      after irradiation, both in the free and protein-bound state, the spectra of
      samples with aquocobalamin and cyanocobalamin changed substantially upon
      irradiation. The spectra of the irradiated samples resembled each other and were
      similar - but not identical - to the spectrum of the reduced cob(II)alamin. The
      implications of these observations for the interpretation of the ;long' axial Co
      N bonds observed crystallographically in B(12) proteins are discussed.

PMID- 16609207
TI  - A novel experimental technique for atomic X-ray holography.
AB  - A new experimental technique for reciprocal X-ray holography has been developed.
      The experimental set-up makes it possible to measure a reciprocal hologram
      without unwanted mixture of the X-ray fluorescence holography signal. The data
      are recorded during continuous rotation of the sample, and are accumulated over
      many revolutions. Thus the sensitivity to fluctuations of the source
      characteristics is reduced. A very high resolution over a large angular range is
      also achieved, which allows recording of X-ray standing-wave shapes near Bragg
      angles. The reconstruction of the measured hologram of a Cu(3)Au crystal gives
      positions of the nearest and next-nearest neighbours of a fluorescing Cu atom.

PMID- 16609208
TI  - Phase-contrast X-ray imaging with a large monolithic X-ray interferometer.
AB  - To increase the field of view for large objects in phase-contrast X-ray imaging,
      a large monolithic X-ray interferometer has been fabricated using an available
      silicon ingot of diameter 10 cm. A performance study of this interferometer has
      been carried out using a synchrotron X-ray source. The view size of the
      interference pattern obtained with this interferometer was 25 mm wide and 15 mm
      high and its visibility was 79%. Various structures of a sliced human
      hepatocellular carcinoma were identified as necrosis, hemorrhagic necrosis,
      normal liver tissue and blood vessel. The performance of this interferometer was
      sufficient for phase-contrast X-ray imaging.

PMID- 16609209
TI  - XAS-Collect: a computer program for X-ray absorption spectroscopic data
      acquisition.
AB  - A computer program for X-ray absorption spectroscopy (XAS) data acquisition,
      called XAS-Collect, is described. The software employs the X Windows system to
      provide a pull-down menu, dialog-box style of graphical user interface. The
      software provides state-of-the-art features while still being sufficiently simple
      for novice users.

PMID- 16609210
TI  - Synchrotron radiation circular-dichroism spectroscopy as a tool for investigating
      protein structures.
AB  - This paper reviews the use of synchrotron radiation circular dichroism (SRCD)
      spectroscopy for examining protein structures, discussing the differences between
      conventional circular dichroism and SRCD, as well as examples of what SRCD
      studies have revealed about protein structures to date. It further discusses the
      future potential of the technique, including roles in structural genomics,
      membrane protein structure elucidation, relationships to crystallographic
      studies, and protein folding and dynamics.

PMID- 16609211
TI  - First results from the Canadian SGM beamline at SRC.
AB  - The first experimental results obtained from the Canadian SGM beamline at SRC
      (Synchrotron Radiation Centre, University of Wisconsin-Madison, USA) are
      reported. The beamline is based on the Dragon-type design, with a constant
      deviation angle, using photons from a second-generation bending-magnet light
      source. The medium-energy grating on this beamline covers a photon energy range
      from 240 to 700 eV, with a ruling density of 600 lines mm(-1). A maximum
      resolving power of approximately 10000 is achieved at a photon energy of
      approximately 400 eV. Gas-phase absorption spectra collected at the N, O and C K
      edges are presented to demonstrate the excellent performance of this beamline.
      High-resolution absorption spectra of some C- and Ti-containing solid-state
      samples are also reported.

PMID- 16609212
TI  - Synchrotron beam test with a photon-counting pixel detector.
AB  - Synchrotron beam measurements were performed with a single-photon-counting pixel
      detector to investigate the influence of threshold settings on charge sharing.
      Improvement of image homogeneity by adjusting the threshold of each pixel
      individually was demonstrated. With a flat-field correction, the homogeneity
      could be improved. A measurement of the point spread function is reported.

PMID- 16609213
TI  - The effect of beam time structure on counting detectors in SRS experiments.
AB  - Counting detector systems are increasingly used in X-ray experiments because of
      their attractive properties as regards linearity, large dynamic range and simple
      noise properties. In synchrotron radiation source (SRS) applications of X-ray
      detectors, counting rates are generally high enough to require dead-time
      correction. The time structure of an SRS beam interacts with the dead-time
      characteristics of the detector in a way that the simple stochastic dead-time
      models cannot always handle. This report generates analytical and Monte Carlo
      mathematical models which describe the rate performance of any given detector
      system when used with the typical beam structures encountered in an SRS.

PMID- 16609214
TI  - Primary radiation damage of protein crystals by an intense synchrotron X-ray
      beam.
AB  - X-ray radiation damage of a lysozyme single crystal by an intense monochromatic
      beam from a third-generation radiation source at the Advanced Photon Source has
      been studied. The results show that primary radiation damage is linearly
      dependent on the X-ray dose even when the crystal is at cryogenic temperatures.
      The existence of an upper limit for the primary radiation damage was observed.
      Above the threshold of approximately 1 x 10(7) Gy, excessive damage of the
      crystal develops which is interpreted as the onset of secondary and/or tertiary
      radiation damage. This upper limit of X-ray dose is compared with Henderson's
      limit [Henderson (1990). Proc. R. Soc. London, B241, 6-8], and its implication
      for the amount of useful X-ray diffraction data that can be obtained for crystals
      of a given scattering power is also discussed.

PMID- 16609215
TI  - Characterization of implanted semiconductors by means of white-beam and plane
      wave synchrotron topography.
AB  - Al(x)Ga(1-x)As epitaxic layers, with x = 0.43 and GaAs single crystals implanted
      with various doses of high-energy Se and Si ions, and silicon single crystals
      implanted with high-energy light ions were studied by means of different X-ray
      diffraction methods employing either a strongly limited white beam or a highly
      collimated monochromatic beam. The methods provided complementary
      characterization of lattice parameter changes and lattice deformation in the
      implanted layers. The synchrotron rocking curves recorded with a small-diameter
      beam provided a very good separation of interference maxima and enabled
      determination of the strain profile. A characteristic difference in strain depth
      distributions between the implanted A(III)B(V) compounds and silicon was noticed.
      Ion implantation in A(III)B(V) compounds produced a relatively thick layer with
      an almost constant and distinctly increased lattice parameter in regions close to
      the surface, whereas, in the case of silicon, shot-through layers with almost
      unchanged lattice spacing were observed. Other important information obtained
      from the synchrotron micro-Laue pattern was that the interference fringes caused
      by crystal curvature or strain gradient are located in the plane of diffraction,
      while parts of the Laue spot corresponding to the deformed regions are usually
      displaced.

PMID- 16609216
TI  - Enhancement of the spin-dependent effect of pi/2-angle Compton scattering using
      elliptically polarized synchrotron radiation.
AB  - Noticeable enhancement of the spin-dependent Compton scattering intensity in
      right-angle scattering has been achieved by using high-energy X-rays having
      elliptical polarization. A promising momentum resolution of better than 0.4
      atomic units for Compton-profile measurements is firmly predicted by means of an
      ordinary Ge solid-state detector when the scattering-angle divergence at 90
      degrees is crucially restricted. It is pointed out that the angle between a
      scattering vector and the direction of sample magnetization can be chosen as 90
      degrees without seriously weakening the spin-dependent effect. Comparison is made
      between 274 keV and 122 keV experiments.

PMID- 16609217
TI  - Wavelength-dispersive double flat-crystal analyzer for inelastic X-ray
      scattering.
AB  - A double flat-crystal analyzer for inelastic X-ray scattering is described. The
      general correlation between the energy and direction of the X-rays transmitted by
      the analyzer allows one to collect data for a range of energy transfers
      simultaneously. Such an analyzer with 120 meV resolution was built to operate at
      the copper K edge. Experimental results show that this X-ray optic can be an
      alternative to a conventional spherical-focusing backscattering analyzer in
      resonant inelastic X-ray scattering experiments or when flexible energy
      resolution or high momentum resolution is required.

PMID- 16609218
TI  - Fixed-exit monochromator for computed tomography with synchrotron radiation at
      energies 18-90 keV.
AB  - A fixed-exit monochromator has been constructed for computed tomography (CT)
      studies at the Medical Beamline of the European Synchrotron Radiation Facility. A
      non-dispersive pair of bent Laue-type crystals is used, and the first crystal is
      water-cooled. The monochromator operates at energies from 18 to 90 keV, and the
      maximum width of the beam is 150 mm. The performance of the monochromator is
      studied with respect to the beam intensity and energy distributions, and a close
      agreement is found between the calculated and experimental results. The intensity
      is between 10(9) and 10(10) photons s(-1) mm(-2) under typical operating
      conditions. The harmonic content of a 25 keV beam is about 30% at the minimum
      wiggler gap of 25 mm (field 1.57 T) and decreases by an order of magnitude when
      the gap is increased to 60 mm (field 0.62 T). The experimental set-up for CT
      studies includes dose monitors, goniometers and translation stages for
      positioning and scanning the object, and a 432-element linear-array Ge detector.
      Examples from phantom studies and in vivo animal experiments are shown to
      illustrate the spatial resolution and contrast of the reconstructed images.

PMID- 16609219
TI  - Breast cancer diagnosis using scattered X-rays.
AB  - Small-angle X-ray diffraction data has been collected from 99 ;core-cut' breast
      tissue specimens representing a number of different pathologies. Data in the
      range 75-1390 A have been compared with controls from patients with no breast
      disease. Bessel functions and Bragg maxima resulting from the fibrillar structure
      of collagen have been identified. The Bragg maxima indexed onto a 649 A lattice.
      Systematic differences in the intensities and D-spacings between the collagen of
      malignant, benign and normal tissue groups have been clearly demonstrated and
      quantified. These differences appear to be due to a significantly lower
      structural order within the malignant tissues. Possible explanations for this are
      discussed and the potential for utilizing this observation in cancer diagnosis is
      considered.

PMID- 16609220
TI  - Phase II of the genomic effort.

PMID- 16609221
TI  - Time-resolved measurements of supersonic fuel sprays using synchrotron X-rays.
AB  - A time-resolved radiographic technique has been developed for probing the fuel
      distribution close to the nozzle of a high-pressure single-hole diesel injector.
      The measurement was made using X-ray absorption of monochromatic synchrotron
      generated radiation, allowing quantitative determination of the fuel distribution
      in this optically impenetrable region with a time resolution of better than 1
      micros. These quantitative measurements constitute the most detailed near-nozzle
      study of a fuel spray to date.

PMID- 16609222
TI  - Visualization, quantification and therapeutic evaluation of angiogenic vessels in
      cancer by synchrotron microangiography.
AB  - The usefulness of a synchrotron microangiography system for depicting,
      quantitating and therapeutically evaluating angiogenic vessels in cancer is
      illustrated. In 20 mice transplanted with murine colon cancer, sequential changes
      in the angiogenic vessels were determined by using synchrotron microangiography,
      using changes in tumor volume for reference. This system allowed the depiction
      and quantification of angiogenic vessels in the period from one to four weeks
      after transplantation. The effects of antiangiogenic therapy were evaluated by
      using a neutralizing antibody against vascular endothelial growth factor. The
      neutralizing antibody partially suppressed angiogenesis and tumor growth.
      Synchrotron microangiography is shown to be useful for the depiction,
      quantification and evaluation of angiogenic vessels in cancer.

PMID- 16609223
TI  - Demonstration of X-ray linear dichroism imaging with hard X-rays.
AB  - X-ray polarization-contrast images resulting from X-ray linear dichroism (XLD) in
      the hard X-ray region have been successfully recorded for the first time. The
      apparatus used consisted of an X-ray polarizer, double X-ray phase retarders and
      a high-spatial-resolution X-ray charge-coupled device (CCD) detector. The sample
      used was a hexagonal close packed (h.c.p.) cobalt single-crystal foil of
      thickness about 12 microm. The experiment was performed at X-ray energies of 23
      and 29 eV above the cobalt K edge (7709 eV), at which the maximum linear
      dichroisms (approximately 3%) were observed, with their signs reversed, in the
      XLD spectrum measured with quadruple X-ray phase retarders. The contrasts in the
      images at the two X-ray energies were reversed as a result of the XLD in the
      sample. Furthermore, the values of the contrast in the images arising from the
      linear dichroism (approximately 3%) were in good agreement with those yielded by
      the XLD spectrum.

PMID- 16609224
TI  - Non-projectiveness of X-ray Pendellosung-fringed diffraction images.
AB  - It has been experimentally found that X-ray moire fringes are not exactly given
      as a projected figure from the specimen crystal as predicted by the standard
      theory of X-ray dynamical diffraction, but show a kind of spatial oscillation
      along the beam path out of the crystal. This paper reports that a similar spatial
      oscillation has been found for Pendellosung fringes in a similar experiment
      recording plane-wave X-ray topographs of a silicon wedge crystal onto a set of
      multi-stacked films. The oscillation of the Pendellosung fringes was easily found
      among the simultaneous topographs on the multi-stacked films by examining the
      fringe profiles, and was also found in topographic images by somewhat careful
      inspection. It is noteworthy that a simple reciprocal correspondence was observed
      between the amplitude of fringe oscillation and the fringe contrast. This finding
      of non-projectiveness, i.e. the fringe oscillation noted above, in Pendellosung
      fringes as well as in moire fringes suggests that the non-projectiveness occurs
      as a very basic property of X-ray interference fringes produced by crystal
      diffraction.

PMID- 16609225
TI  - X-ray diffraction on Si single crystal with a W-shaped longitudinal groove.
AB  - The measurement of the sagittal deviation of an X-ray beam diffracted on the
      inclined surface of an Si(111) single crystal was performed on beamline BM5 at
      the ESRF, with lambda = 0.1 nm and an inclination angle, beta, of 70 degrees .
      The measured value agrees with the theory developed in previous papers. The
      topographic picture of the longitudinal edge shows a structure that can be
      explained in terms of the properties of inclined diffraction.

PMID- 16609226
TI  - Integration of macromolecular diffraction data using radial basis function
      networks.
AB  - This paper presents a novel approach for intensity calculation of X-ray
      diffraction spots based on a two-stage radial basis function (RBF) network. The
      first stage uses pre-determined reference profiles from a database as basis
      functions in order to locate the diffraction spots and identify any overlapping
      regions. The second-stage RBF network employs narrow basis functions capable of
      local modifications of the reference profiles leading to a more accurate observed
      diffraction spot approximation and therefore accurate determination of spot
      positions and integrated intensities.

PMID- 16609227
TI  - Illumination for coherent soft X-ray applications: the new X1A beamline at the
      NSLS.
AB  - The X1A soft X-ray undulator beamline at the NSLS has been rebuilt to serve two
      microscopy stations operating simultaneously. Separate spherical-grating
      monochromators provide the resolving power required for XANES spectroscopy at the
      C, N and O absorption edges. The exit slits are fixed and define the coherent
      source for the experiments. The optical design and the operational performance
      are described.

PMID- 16609228
TI  - Transmission phase gratings for EUV interferometry.
AB  - The performance of the recently developed EUV phase-shifting point diffraction
      interferometer (PS/PDI) depends heavily on the characteristics of the grating
      beamsplitter used in the implementation. Ideally, such a grating should provide
      throughput of better than 25% and diffraction efficiency, defined as the ratio of
      the first-diffracted-order power to the zero-order power, variable in the range
      from approximately 10 to 500. The optimal method for achieving these goals is by
      way of a phase grating. Also, PS/PDI system implementation issues favor the use
      of transmission gratings over reflection gratings. Here, the design, fabrication,
      and characterization of a recently developed transmission phase grating developed
      for use in EUV interferometry is described.

PMID- 16609265
TI  - Immunolocalization of water channel aquaporins in the nasal olfactory mucosa.
AB  - Aquaporins (AQPs), membrane water channel proteins expressed in various tissues
      and organs, serve in the transfer of water and small solutes across the membrane.
      We raised antibodies to AQPs using isoform-specific synthetic peptides and
      surveyed their expression in the rat nasal olfactory and respiratory mucosae.
      AQP1, AQP3, AQP4, and AQP5 were detected by immunohistochemical and
      immunoblotting analyses. AQP1 was expressed in the endothelial cells of blood
      vessels and the surrounding connective tissue cells in the olfactory and
      respiratory mucosae. AQP1 may be involved in water transfer across the blood
      vessel wall. In the olfactory epithelium, no AQP was detected in the olfactory
      sensory cells. Instead, AQP3 was abundant in the olfactory epithelium, where it
      was localized in the supporting cells and basal cells. Expression of AQP3 was
      mostly restricted to the basal cells in the respiratory epithelium. In marked
      contrast, AQP4 was abundant in the respiratory epithelium, but its abundance was
      limited to the basal cells in the olfactory epithelium. In the Bowman's gland,
      AQP5 was localized in the apical membrane in the secretory acinar cells, whereas
      AQP3 and AQP4 were found in the basolateral membrane. Similar localization was
      seen in its duct cells. These results showed a distinct localization pattern for
      AQPs in the olfactory epithelium. AQP3 and AQP4 in the supporting cells and basal
      cells may play an important role in generating and maintaining the specific
      microenvironment around the olfactory sensory cells. AQP3, AQP4, and AQP5 in the
      Bowman's gland may serve in the secretion to generate the microenvironment at the
      apical surface of the olfactory dendrites for odorant reception.

PMID- 16609266
TI  - Exposure to aluminium changes the NADPH-diaphorase/NPY pattern in the rat
      cerebral cortex.
AB  - Aluminium (Al) impairs the glutamate-nitric oxide-cGMP pathway and reduces the
      number of nitroxidergic neurons in the rat somatosensory cortex. To understand
      better the effect of the time of exposure, we monitored the effect of aluminium
      administration on nitroxidergic neurons, identified by NADPH-diaphorase (NADPH-d)
      or by nitric oxide synthase (NOS) staining, after 0.5, 1, 2, 3, 6 and 12 months
      of aluminium administration. Since neuropeptide Y (NPY) is known to be
      colocalised with nitric oxide synthase in cortical neurons, the aim of this work
      was to study the effects of Al administration on the cortical expression of NADPH
      d, nNOS, and NPY. NADPH-d or NOS positive neurons were found scattered in the
      cortex where they constituted about 1% of all neurons. Double staining using
      NADPH-d and NPY showed that almost all nitroxidergic neurons were co-localised
      with NPY neurons (NADPH-d/NPY double stained neurons) whereas some neurons were
      stained only with NPY (NPY single stained neurons) ; these were more numerous
      than NADPH-d/NPY double stained neurons. Al significantly reduced NADPH-d and
      nNOS positive neurons in the cerebral cortex time dependently, with the greatest
      effect appearing after 3 months. Also measured was the integrated optical density
      (IOD) of nNOS positive neurons showing a significant decrease of NOS
      immunostaining even in the remaining NOS positive neurons. The double staining
      experiment exhibited a decrease in NADPH-d/NPY double stained neurons with an
      apparent increase in NPY single stained neurons; these then decreased after 6-12
      months. On the whole, the results confirm that Al impairs nitroxidergic pathways
      time dependently; moreover, the transient increase in NPY single stained neurons
      from 1 to 3 months suggests that there is an intraneuronal down-regulation of
      NOS, without affecting neuronal viability. In addition, the decrease in the NPY
      system found at 6 and 12 months may indicate that Al affected nitroxidergic and
      NPY systems at different times.

PMID- 16609267
TI  - Requirement of a bone morphogenetic protein for the maintenance and stimulation
      of osteoblast differentiation.
AB  - The requirement of a bone morphogenetic protein for the maintenance and
      stimulation of an osteoblast phenotype was examined using mouse MC3T3-E1 cell
      cultures. Cells expressed BMP-4 mRNA, which correlated with the stimulation of
      the osteoblast phenotype. The addition of a BMP-4 specific antibody reduced bone
      nodules, suggesting that BMP-4 is required for the osteogenic activity of
      osteoblasts in an autocrine manner. Exogenously added BMP-7 gradually decreased
      the expression of BMP-4 with a concurrent stimulation of the osteoblast
      phenotype. Exogenous BMP-7 can therefore substitute for endogenously produced BMP
      4 acting as a paracrine factor on osteoblasts. The addition of 17beta estradiol
      decreased BMP-4 expression but initiated synthesis of BMP-6 mRNA, an endocrine
      signal for osteoblasts, which also substituted for the lack of endogenous BMP-4,
      as evidenced by normal bone nodule formation. The addition of dexamethasone and
      parathyroid hormone did not affect the BMP-4 expression but induced transcripts
      for BMP-2 and BMP-3, respectively, suggesting that their effects on bone can be
      in part achieved via the BMP signaling. These experiments support the requirement
      of a BMP for osteoblast differentiation and function, demonstrating for the first
      time that a BMP can functionally substitute for another BMP in an
      autocrine/paracrine manner or mediate a response to an endocrine action on
      osteoblasts.

PMID- 16609268
TI  - Evidence of antibody production in the rat cervical lymph nodes after antigen
      administration into the cerebrospinal fluid.
AB  - We previously showed histologically that, in the rat, the cerebrospinal fluid
      drains from the subarachnoid space along the olfactory nerves to the nasal
      lymphatics and empties into the superficial and deep cervical lymph nodes. The
      present study was performed to investigate whether these lymph nodes play a role
      in the immune response of the central nervous system. For this purpose, keyhole
      limpet hemocyanin conjugated with fluorescein isothiocyanate (KLH-FITC) was
      administered into the subarachnoid space of the rat brain, and the time-kinetics
      and location of FITC and anti-FITC antibody forming cells in the cervical lymph
      nodes were studied histologically and immunohistochemically. FITC fluorescence
      was detected in superficial and deep cervical lymph nodes as well as the
      subarachnoid space and the nasal mucosa 2 h after FITC-KLH injection into the
      subarachnoid space. The specific antibody-forming cells first appeared in both
      the superficial and deep cervical lymph nodes on the 4th day after antigen
      administration although the reaction was more intense in the deep than in the
      superficial cervical lymph nodes. These cells were located in the medullary cords
      of the cervical lymph nodes. The number of antibody forming cells increased
      thereafter, reached a peak around the day 6, and then declined on day 10. These
      findings indicate that antigens introduced in the cerebrospinal fluid are drained
      into the cervical lymph nodes through the nasal lymphatics and initiate the
      antigen-specific immune response there. Thus, the cervical lymph nodes probably
      act as a monitoring site for cerebrospinal fluid and play a major role in the
      central nervous system immune response.

PMID- 16609269
TI  - The role of protease-activated receptors on the intracellular calcium ion
      dynamics of vascular smooth muscles, with special reference to cerebral
      arterioles.
AB  - Protease-activated receptors (PARs) mediate cellular responses to various
      proteases in numerous cell types, including smooth muscles and the endothelium of
      blood vessels. To clarify whether the stimulation of PARs induces responses in
      smooth muscle cells of cerebral arterioles, intracellular Ca2+([Ca2+]i) dynamics
      and nitric oxide (NO) production during PARs stimulation were investigated in the
      rat cerebral arterioles by real-time confocal microscopy, since [Ca2+]i and NO
      are both key factors in the maintenance of strain in blood vessels. Testicular
      arterioles were also investigated for comparison. In smooth muscle cells of small
      cerebral arterioles (< 50 microm in diameter), thrombin and PAR1-activating
      peptide (AP) induced an increase in [Ca2+]i and contraction. The response to PAR1
      activation was caused by Ca2+ mobilization from intracellular Ca2+ stores.
      Trypsin and PAR2-AP induced a decrease in [Ca2+]i in the cells which was
      considered to be mediated by endothelium-derived NO and/or by promoting a Ca2+
      sequestration mechanism. PAR3- and 4-AP had little effect. In contrast to small
      cerebral arterioles, [Ca2+]i dynamics in smooth muscle cells of large cerebral
      arterioles (< 150 microm in diameter) or testicular arterioles remained unchanged
      during PARs activation. The effects of PARs activation on the [Ca2+]i dynamics
      and the contraction/relaxation of cerebral arterioles are also discussed in
      relation to the role of proteases in the regional tissue circulation of the
      brain.

PMID- 16609270
TI  - Expression of NCAM in activated portal fibroblasts during regeneration of the rat
      liver after partial hepatectomy.
AB  - In the portal tract of the regenerating liver after partial hepatectomy, vascular
      and bile ductular remodeling takes place in response to the portal hyperdynamic
      state and parenchymal hyperplasia. In order to reveal phenotypical changes in the
      portal fibroblasts, we immunohistochemically investigated neural cell adhesion
      molecules (NCAM) and alpha smooth muscle actin (alphaSMA) expression and the
      ultrastructural changes in them during liver regeneration. In the control rat
      liver, portal fibroblasts were negative for both NCAM and alphaSMA. They became
      positive for both markers two days after partial hepatectomy, increased in
      staining intensity, reached a maximum at three to four days, then decreased,
      being still clearly positive at 14 days. Under an electron microscope, portal
      fibroblasts from the regenerating liver had larger amounts of cytoplasm and rough
      endoplasmic reticulum than those from the control liver; thus they might be
      activated. Additionally, periportal hepatic stellate cells in the regenerating
      liver were activated with alphaSMA, but without NCAM. The present study has
      demonstrated that portal fibroblasts express NCAM and alphaSMA in the
      regenerating liver after partial hepatectomy via transformation into
      myofibroblasts following reconstruction of the portal tracts.

PMID- 16609271
TI  - Atomic force microscopy of native human metaphase chromosomes in a liquid.
AB  - The present study introduces a method for obtaining three-dimensional images of
      native (i.e., unfixed) chromosomes by atomic force microscopy (AFM) in a liquid.
      Human metaphase chromosomes were isolated from a human lymphoblast-like cell
      line, K562, by the hexylene glycol procedure according to Wray and Stubble- field
      (1970), adsorbed on a silane-coated glass slide, and observed in a dynamic force
      mode (i.e., intermittent contact mode) of AFM in a hexylene buffer solution. In
      adequate operating conditions, the shape of chromosomes with paired chromatids
      was clearly and three-dimensionally observed by AFM. At high magnification,
      globular or fibrous structures about 50 nm thick could be found on the surface of
      each chromaid, implying that chromatin fibers were strongly wound or twisted in
      the chromatid. Thus, AFM imaging enabled the direct visualization of native
      chromosomes in a liquid at high resolution--which is comparable with that of
      scanning electron microscopy--and can serve to analyze the mechanism of
      chromosome condensation and separation in relation to the structure of
      chromosomes.

PMID- 16609272
TI  - Antigenicity and irritancy tests of leukocyte-reduction filters using animal
      models.
AB  - We experienced a patient who showed severe allergic symptoms immediately after
      blood transfusion using a filter for removal of leukocytes. To investigate the
      cause of this incident, we conducted a maximization test on the antigenicity of
      substances extracted from filters used for leukocyte removal. The tests were
      performed in guinea pigs. Acetone extracts were obtained from filters made by
      three manufacturers (A, B and C) and sensitization and evocation were tested at
      10% concentration. It was confirmed that extracts from one filter (B) induced
      sensitization in guinea pigs. Sensitization of the extracts was also tested at
      1%, 0.1% and 0.01%, and was induced at 1% but not at 0.1% and 0.01%. Next, skin
      irritation and sensitization of the substances were tested using mice. 5%-ethanol
      extracts were prepared from filters made by 2 manufacturers (A and B) and the
      extracts (5% or 0.5% concentrations) were injected intradermally into the auricle
      and the ear swelling was observed 1, 24 and 48 hours and 7 days after injection.
      Significant ear swelling was induced by the extracts from B-filters. In the skin
      sensitization test, 5% extracts were injected subcutaneously into the back of
      mice for 3 continuous days for sensitization, and 0.5% extracts were injected
      intradermally into the auricle of mice to evoke a response, after which changes
      in ear swelling were observed. Biphasic ear swelling observed 1 hour (immediate
      response) and 24 hours (delayed response) after challenge was induced by the
      extracts from B-filters. In conclusion, our study showed that filters used for
      leukocyte removal may contain substances that cause skin irritation and
      sensitization and that antigenicity and irritancy tests of the filters might
      prevent the adverse reactions after blood transfusion.

PMID- 16609273
TI  - Impaired response of perforating arteries to hypercapnia in chronic
      hyperglycemia.
AB  - Diabetes mellitus increases the risk of cerebrovascular disease, the effects of
      hypercapnia on CBF (cerebral blood flow) and cerebrovascular reactivity during
      diabetes are still inconsistent. Here, we have established a new
      microangiographic technique using synchrotron radiation (SPring-8, Japan), which
      enabled us to visualize rat cerebral vessels with high spatial resolution in real
      time. The goal of the study presented here was to identify the effects of chronic
      hyperglycemia on hypercapnia-induced vascular responses (endothelium-dependent
      vasodilatation) and nitric oxide (NO) donor- induced vascular responses
      (endothelium-independent) of perforating arteries and of the deeply located large
      cerebral arteries. We found a significant vasodilatation of rat perforating
      arteries after hypercapnia with a maximum diameter of approximately 140% of
      baseline in normal Wistar rats. Chronic hyperglycemia impaired vasodilatation of
      perforating arteries in genetically diabetic GK rats. SNP (sodium nitroprusside)
      caused a similar vasodilatation of perforating vessels in normal and chronic
      hyperglycemia, indicating that endothelium-dependent vasodilatation of
      perforating arteries may be specifically impaired in chronic hyperglycemia.
      Possible impairment of endothelium-dependent vasodilatation in perforating
      vessels during chronic hyperglycemia may cause decreased vascular reserve
      capacity of perforating artery, resulting in the increased ischemic insults and
      cerebrovascular diseases in diabetes.

PMID- 16609274
TI  - A clinical nurse specialist agenda for patient safety.

PMID- 16609277
TI  - The randomized controlled trial: basic considerations.

PMID- 16609278
TI  - Bird flu pandemic and Tamiflu: implications for the clinical nurse specialist.

PMID- 16609279
TI  - Community-based research to explore safer sex behaviors among women: implications
      for CNS practice.
AB  - PURPOSE/OBJECTIVES: This article illustrates how data from community-based
      surveys can be used to inform clinical nurse specialist (CNS) practice and
      ultimately influence patient care related to sex behaviors. BACKGROUND/RATIONALE:
      Clinical nurse specialists design, implement, and evaluate research to develop
      specific prevention and intervention strategies for populations. Much of this
      research is conducted in the tertiary setting although many of the interventions
      are carried out in the community setting. DESCRIPTION OF THE PROJECT: A sample of
      rural women (N = 578) participated in a community-based survey to determine
      characteristics which influence safer sex behaviors. OUTCOME: Results of the
      survey suggest that age, education, and relationship status influence safer sex
      behaviors. Women in the community tended to believe that safer sex behaviors were
      linked to pregnancy prevention and lacked understanding about the importance of
      safer sex behaviors to prevent sexually transmitted diseases including HIV/AIDS.
      INTERPRETATION/CONCLUSION: The findings of this study can inform CNSs about sex
      behaviors among women in a selected community, translating community-based
      research into evidence-based, patient-centered care. IMPLICATIONS FOR NURSING
      PRACTICE: Results from community-based research can be used to develop
      educational and prevention programs, and interventions for specialty populations.

PMID- 16609281
TI  - Achieving clinical nurse specialist competencies and outcomes through
      interdisciplinary education.
AB  - Without formal education, many healthcare professionals fail to develop
      interdisciplinary team skills; however, when students are socialized to
      interdisciplinary practice through academic clinical learning experiences,
      effective collaboration skills can be developed. Increasingly, educational
      environments are challenged to include clinical experiences for students that
      teach and model interdisciplinary collaboration. PURPOSE: The purpose of this
      quality improvement initiative was to create an interdisciplinary educational
      experience for clinical nurse specialist (CNS) students and postgraduate
      physicians. DESCRIPTION OF THE PROJECT: The interdisciplinary learning
      experience, supported by an educational grant, provided an interdisciplinary
      cohort of learners an opportunity to engage in a clinically focused learning
      experience. The interdisciplinary cohort consisted of CNS students and physicians
      in various stages of postgraduate training. The clinical experience selected was
      a quality improvement initiative in which the students were introduced to the
      concepts and tools of quality improvement. During this 1-month clinical
      experience, students applied the new skills by implementing a quality improvement
      project focusing on medication reconciliation in the outpatient setting. The CNS
      core competencies and outcomes were used to shape the experience for the CNS
      students. OUTCOME: The CNS students exhibited 5 of the 7 essential
      characteristics of the CNS (leadership, collaboration, consultation skills,
      ethical conduct, and professional attributes) while demonstrating competencies
      and fulfilling performance expectations. During this learning experience, the CNS
      students focused on competencies and outcomes in the organizational sphere of
      influence. Multiple facilitating factors and barriers were identified.
      CONCLUSION: This interdisciplinary clinical experience in a quality improvement
      initiative provided valuable opportunities for CNS students to develop essential
      CNS characteristics and to explore practice competencies in the area of systems.
      IMPLICATIONS: Interdisciplinary clinical experiences offer students opportunities
      to develop needed collaboration and communication skills. Educators should create
      interdisciplinary educational experiences for students to better prepare them for
      their roles in a clinical setting.

PMID- 16609283
TI  - Socializing clinical nurse specialist students for practice.

PMID- 16609284
TI  - Tillis' "healing sounds".

PMID- 16609287
TI  - Diabetic nephropathy: leveraging mouse genetics.
AB  - PURPOSE OF REVIEW: Advances in mouse genetics have made this species particularly
      useful as a model for human disease. This review will summarize recent advances
      regarding the pathogenesis of diabetic nephropathy discovered in mice. RECENT
      FINDINGS: Diabetic nephropathy has been characterized in novel genetic models of
      murine diabetes including the Akita, Ove26, and ICER-Igamma mice. Mutagenesis
      resources targeting every gene of the genome and the importance of inbred genetic
      background are discussed. SUMMARY: Through the use of these resources mouse
      models should provide new insight into the pathogenesis of diabetic nephropathy,
      and complement human studies and validate the identity of candidate genes
      contributing to diabetic nephropathy.

PMID- 16609288
TI  - Animal models of HIV-associated nephropathy.
AB  - PURPOSE OF REVIEW: HIV-1-associated nephropathy is characterized clinically by
      proteinuria with azotemia and pathologically by collapsing focal segmental
      glomerulosclerosis with tubulointerstitial nephritis and microcystic tubular
      dilatation. This review summarizes the manner in which different transgenic
      animal models contribute to our knowledge of the pathogenesis of HIV-1-associated
      nephropathy. RECENT FINDINGS: The most widely studied has been a transgenic mouse
      model bearing a gag and pol-deleted proviral construct that develops renal
      disease with many of the clinical and pathologic characteristics seen in HIV-1
      associated nephropathy. Studies using this model have helped to highlight the
      role of HIV-1 viral gene expression in renal cells, podocyte dysregulation, and
      genetic host factors in the pathogenesis of HIV-1-associated nephropathy. This
      model has provided the key insights that led to detection of HIV-1 in human
      kidney epithelial cells. Other transgenic models have helped define critical
      roles for individual HIV gene products (Nef and Vpr) in the pathogenesis of HIV-1
      associated nephropathy. Transgenic mouse models have also provided a method to
      discover new treatments targeting various steps in the pathogenesis of this
      disease. SUMMARY: Transgenic animal models of HIV-1-associated nephropathy have
      contributed greatly to the progress made toward understanding the pathogenesis of
      this disease.

PMID- 16609289
TI  - Stem cells and kidney injury.
AB  - PURPOSE OF REVIEW: The most commonly used therapies in nephrology target the
      reduction of acute injury, reduction of the rate of progression, or renal
      replacement therapy. The purpose of this review is to examine new evidence that
      renal progenitors can be used for therapeutic purposes. Stem cells possess two
      characteristics, self-renewal and the capacity for multilineage differentiation.
      They are typically classified as derived from embryos or from the adult. RECENT
      FINDINGS: New studies on embryonic stem cells show that they can be use to enrich
      for specific renal progenitors, which integrate into mature structures. Studies
      on adult stem cells show that almost all kidney cell types can be renewed by
      adult stem cells originating in bone marrow. Moreover, some animal studies
      demonstrate that a phenotype such as the aging and diabetic phenotype can be
      transferred from progenitors residing in the bone marrow, suggesting that the
      bone marrow contains renal progenitors that may be useful for therapeutic
      purposes. SUMMARY: Stem cell therapy opens the door to regenerative nephrology.
      Embryonic stem cells are a useful tool to determine the pathways to convert a
      pluripotent stem cell into renal progenitors. Adult stem cells in the bone marrow
      or in a specific kidney niche may provide a source of stem cells with a
      therapeutic potential.

PMID- 16609290
TI  - Cilium-generated signaling: a cellular GPS?
AB  - PURPOSE OF REVIEW: The discovery of the importance of proteins localized to cilia
      and basal bodies has provided novel insights into the pathogenesis of various
      human disorders including cystic kidney disease. The physiological role of cilium
      generated signaling in most tissues including the kidney has remained elusive,
      however. This review focuses on the most recent advance in understanding a role
      for signaling through cilia for kidney biology. RECENT FINDINGS: Recent work has
      tied the function of several developmental master regulators to cilium-generated
      signaling in vertebrates. Hedgehog signaling requires ciliary proteins and loss
      of targeting of its receptors and effectors to cilia abrogates Hedgehog function.
      Moreover, the ciliary protein inversin has been shown to act as a molecular
      switch for the regulation of Wnt signaling cascades. SUMMARY: Together with
      recent data on a function of cilia and basal body proteins in planar cell
      polarity in mice, a novel concept and testable hypothesis for the function of
      cilia in vertebrates is emerging: cilia may act as a cellular positioning device
      to allow subcellular asymmetry and polarization of the cells within the plane of
      the epithelium to develop and maintain regular arrays of cells such as kidney
      tubes.

PMID- 16609291
TI  - Progression of chronic kidney disease: insights from animal models.
AB  - PURPOSE OF REVIEW: Chronic kidney diseases are emerging as a worldwide public
      health problem. Clarification of the mechanisms underlying progression of
      proteinuric nephropathies received significant input from the generation of
      transgenic and knockout animals and from novel approaches to block mediators of
      injury. Reviewed here are advances in animal models used as a tool to address
      some relevant questions to the pathophysiology of human chronic nephropathies.
      RECENT FINDINGS: Gene targeting in rodents identified podocyte loss as central
      event in the development of glomerulosclerosis. The trigger is dysfunction or
      absence of podocyte molecules that stabilize the slit diaphragm or anchor foot
      processes to the basement membrane. Sustained injury of the glomerular barrier to
      proteins is transmitted to the tubulointerstitial compartment leading to
      inflammation and fibrosis. Blocking NF-kappaB activity and chemokine signals in
      the kidney effectively interrupts such process. Growth factors produced by
      tubular cells and inflammatory cells contribute to interstitial fibrogenesis via
      myofibroblast activation. SUMMARY: Development of genetically engineered animals
      and techniques to specifically manipulate cellular mediators has highlighted the
      determinants of glomerulosclerosis and tubulointerstitial injury. This knowledge
      will provide basis for novel interventions to protect the podocyte in chronic
      progressive glomerulopathies and to halt renal scarring and loss of function.

PMID- 16609292
TI  - New insights into the pathogenesis of membranous glomerulonephritis.
AB  - PURPOSE OF REVIEW: Membranous nephropathy is one of the most common
      glomerulopathies. Current treatments are entirely empirical, and concept-driven
      therapies are dramatically lacking. This review focuses on new pathophysiologic
      aspects of the disease, with special emphasis on the antigenic targets of
      pathogenic antibodies. RECENT FINDINGS: Neutral endopeptidase - a podocyte
      antigen that can digest biologically active peptides - was recently identified as
      the target antigen of antibodies deposited in the subepithelial space of
      glomeruli in a subset of patients with antenatal membranous nephropathy. The
      mothers became immunized because they are deficient in neutral endopeptidase due
      to truncating mutations in the gene. Membranous nephropathy could be transferred
      to the rabbit by injection of mothers' immunoglobulin. Development of the renal
      disease was associated with anti-neutral endopeptidase IgG1. SUMMARY: Membranous
      nephropathy most likely is a heterogeneous disease, although a common denominator
      may be that podocytes provide antigenic targets for in-situ formation of
      glomerular immune deposits. Identification of neutral endopeptidase and
      additional (podocyte) antigens and characterization of their epitopes should make
      it possible to design more effective and better tolerated therapies. Fetomaternal
      alloimmunization is a novel mechanism of renal disease that may apply to other
      organs as well.

PMID- 16609293
TI  - New insights into the epidemiology of chronic kidney disease in US Asians and
      Pacific Islanders.
AB  - PURPOSE OF REVIEW: In contrast to advances in our understanding of health
      disparities in other ethnic groups within the US, differential outcomes
      associated with chronic kidney disease among US Asians have gone largely
      unexamined. Until recently, risk estimates for chronic kidney disease outcomes
      among US Pacific Islanders were virtually unknown. This review highlights recent
      contributions to our understanding of chronic kidney disease outcomes in US
      Asians and Pacific Islanders. RECENT FINDINGS: Asians in the US appear to have a
      higher risk of end-stage renal disease relative to US whites after accounting for
      baseline kidney disease and many of the known risk factors for end-stage renal
      disease. The origins of the discrepancy in risk for end-stage renal disease
      between US Asians and whites do not appear to be explained by the socioeconomic
      and comorbidity disparities paradigm present in the US black vs. white model.
      Mounting evidence suggests that US Asians and Pacific Islanders receive
      substantially less predialysis care and proportionally fewer kidney transplants
      compared with US whites. Paradoxically, these populations have equivalent or
      better survival on dialysis. SUMMARY: These data highlight the need for studies
      to elucidate the mechanisms underlying the differential outcomes observed among
      US Asians and Pacific Islanders. Efforts to identify ethnicity-specific risk
      factors for kidney disease and interventions aimed at promoting predialysis care
      and kidney transplantation among US Asians and Pacific Islanders could
      substantially reduce morbidity, mortality, and costs.

PMID- 16609294
TI  - Update on cystatin C: new insights into the importance of mild kidney
      dysfunction.
AB  - PURPOSE OF REVIEW: Using cystatin C, a novel serum marker of kidney function,
      several studies have shown that mild kidney dysfunction is associated with
      increased risk for cardiovascular disease and mortality. Studies have questioned,
      however, whether cystatin C is predominantly a measure of kidney function. This
      review summarizes the research literature on cystatin C. RECENT FINDINGS: One
      longitudinal study in patients with diabetes found cystatin C to approximate
      glomerular filtration rate measures over 4 years much better than creatinine.
      Studies in several cohorts found cystatin C to be linearly associated with
      mortality, cardiovascular mortality, and heart failure risk, whereas creatinine
      predicted increased risk only in subjects with the worst kidney function. One
      study, however, found that increased age, male sex, increased height and weight,
      smoking, and higher C-reactive protein levels were associated with cystatin C
      after adjustment for creatinine clearance, which may suggest nonrenal influences
      on cystatin C concentrations. SUMMARY: Cystatin C appears to capture the
      association of mild kidney dysfunction with increased risk for cardiovascular
      disease and death. Future research needs to evaluate whether cystatin C will have
      an important role in clinical medicine.

PMID- 16609295
TI  - Kidney function estimating equations: where do we stand?
AB  - PURPOSE OF REVIEW: Estimation of the glomerular filtration rate (GFR) is central
      to the diagnosis, evaluation and management of chronic kidney disease. This
      review summarizes recent data on the performance of equations using serum
      creatinine to estimate the GFR, particularly the Modification of Diet in Renal
      Disease (MDRD) Study equation. RECENT FINDINGS: During 2005 GFR estimation has
      received substantial attention with a focus on comparing the MDRD Study equation
      with the Cockcroft-Gault equation. Several large studies (n>500) have appeared.
      Most studies discuss creatinine calibration but few were able to standardize
      measurements. Studies that did calibrate the creatinine had improved performance.
      Overall, the MDRD Study equation performed well in populations with a low range
      of GFR and often outperformed the Cockcroft-Gault equation. Both equations have
      lower precision in high GFR populations, and the MDRD equation under-estimated
      the GFR in a number of studies. Efforts are underway to develop improved
      prediction equations by pooling data across many study populations. SUMMARY:
      Equations for estimating the GFR from serum creatinine are useful for systematic
      staging of chronic kidney disease. The MDRD Study equation and systematic
      creatinine assay calibration improve the level of precision and accuracy in many
      settings. GFR estimates are less useful in the normal range of GFR, however, and
      are sensitive to the population under study.

PMID- 16609296
TI  - Strategies to reduce the risk of contrast nephropathy: an evidence-based
      approach.
AB  - PURPOSE OF REVIEW: Contrast nephropathy is a common complication associated with
      angiographic procedures that carries significant morbidity and mortality. Recent
      clinical trials of prophylactic strategies have reported contradictory results.
      This review presents recent insights into the pathophysiology of contrast
      nephropathy and reviews trial results in this context. RECENT FINDINGS: A
      prediction rule has been developed to better identify patients at risk of
      developing contrast nephropathy. Factors other than osmolality play a significant
      role in the pathogenesis of contrast nephropathy, at least for agents with
      osmolalities of 800 mOsm/kg or less. New randomized trial data do not support a
      role for N-acetylcysteine in contrast nephropathy prophylaxis and there is
      additional evidence that fenoldopam is ineffective. Pooled analyses of
      theophylline prophylaxis trials are inconclusive. Theoretical and clinical data
      suggest that ascorbic acid may be renoprotective, but this requires further
      study. SUMMARY: The overall incidence of contrast nephropathy remains low.
      Available evidence supports the use of hydration and low volumes of iso-osmolar
      or low-osmolar contrast in patients at risk of developing contrast nephropathy.
      Heterogeneity has affected interpretability of interventional trials of N
      acetylcysteine or theophylline prophylaxis strategies. Future clinical trials
      must identify and target moderate-risk to high-risk patients and ensure that
      proven therapies are included in trial protocols.

PMID- 16609297
TI  - Hypertension and kidney disease in Asia.
AB  - PURPOSE OF REVIEW: Communicable diseases were traditionally the major cause of
      public health concern in Asian countries, most of which were less developed. With
      industrialization and associated lifestyle changes during the past few decades,
      however, noncommunicable diseases similar to those that affect Western societies
      have emerged in Asian countries. The purpose of the review was to examine recent
      evidence about the burden and factors associated with hypertension and chronic
      kidney disease (CKD) in Asian countries. RECENT FINDINGS: Hypertension has become
      one of the leading causes of mortality in Asia. Although its prevalence continues
      to rise, it remains under-diagnosed and under-treated. CKD is becoming
      increasingly common mainly due to an increase in risk factors such as high blood
      pressure, diabetes, and obesity. Treatment of advanced CKD is overwhelmingly
      burdensome in a resource poor environment. Barriers to early detection of CKD in
      Asians include the fact that equations to estimate the glomerular filtration rate
      have not been validated in this population, and the uncertainty about appropriate
      glomerular filtration rate cutoff values to define CKD. SUMMARY: Concerted
      efforts are needed to develop and implement cost-effective strategies for
      prevention and treatment of hypertension and CKD in Asian countries. More
      research is needed on these conditions in these populations.

PMID- 16609298
TI  - Epidemiology of non-dialysis-requiring chronic kidney disease and cardiovascular
      disease.
AB  - PURPOSE OF REVIEW: To review recent literature about the relationship between non
      dialysis-requiring chronic kidney disease and cardiovascular disease as well as
      possible explanatory factors. RECENT FINDINGS: Reduced estimated glomerular
      filtration rate below 60 ml/min/1.73 m independently predicts the risk of death
      and cardiovascular events in persons with or without known cardiovascular disease
      as well as those undergoing coronary or peripheral arterial revascularization.
      This risk is not linearly associated with level of kidney function. Chronic
      kidney disease is associated with a larger burden of traditional vascular risk
      factors but is also linked to abnormalities in a variety of nontraditional
      pathways such as dysregulation of mineral metabolism and arterial calcification,
      vessel stiffness and endothelial dysfunction, insulin resistance, inflammation,
      malnutrition, and anemia, among others. Other novel kidney-specific proteins
      (e.g. renalase) may play direct mediating roles. The relative contribution of
      these factors to excess cardiovascular disease in chronic kidney disease remains
      unclear. SUMMARY: Recent evidence demonstrates the importance of non-dialysis
      requiring chronic kidney disease as a potent predictor of cardiovascular disease
      and its complications. Randomized trials should be performed to determine whether
      modification of traditional and nontraditional risk factors can reduce incident
      cardiovascular disease as well as which interventions can optimize treatment
      outcomes in persons with chronic kidney disease and cardiovascular disease.

PMID- 16609299
TI  - Which drug should be used to treat patients with uncomplicated essential
      hypertension?
AB  - PURPOSE OF REVIEW: To review recent data and guidelines on selecting the initial
      antihypertensive drug. RECENT FINDINGS: The main driver of benefit from blood
      pressure-lowering therapy is blood pressure reduction, and there is little
      evidence supporting additional drug class-specific benefits in primary prevention
      of major cardiovascular outcomes. The results also confirm that in the patient
      with uncomplicated hypertension as well as in those patients with diabetes
      without nephropathy, initial therapy with 'newer therapies' (i.e. angiotensin
      converting enzyme inhibitors, calcium channel blockers, and angiotensin receptor
      blockers) are effective, but not more effective than thiazide diuretics, at
      reducing stroke, coronary heart disease, morbidity or mortality, or all-cause
      mortality. SUMMARY: While compelling indications may exist for specific drug
      classes in those with specific target organ damage (i.e. heart failure, renal
      insufficiency, and coronary artery disease), thiazide diuretics remain
      unsurpassed in lowering blood pressure and in preventing hypertension-related
      clinical outcomes. Despite a more favorable metabolic profile, alpha-blockers are
      less effective in preventing cardiovascular disease, especially heart failure and
      stroke. Calcium channel blockers produce a similar reduction in blood pressure
      and cardiovascular disease outcomes compared with thiazide-type diuretics,
      although they are consistently less effective in preventing heart failure. In the
      absence of heart failure or renal disease, angiotensin-converting enzyme
      inhibitors have shown little advantage in clinical trials over diuretics in
      preventing cardiovascular disease and are not indicated as an initial therapy in
      Blacks.

PMID- 16609300
TI  - Hypertension diagnosis and prognosis in chronic kidney disease with out-of-office
      blood pressure monitoring.
AB  - PURPOSE OF REVIEW: Hypertension is an important risk factor for adverse
      cardiovascular and renal outcomes particularly in patients with chronic kidney
      disease. This review compares blood pressure measurements obtained in the clinic
      with those obtained outside the clinic to predict cardiovascular and renal injury
      and outcomes. RECENT FINDINGS: When home blood pressure monitoring (self-measured
      blood pressure) is performed, hypertension is less frequently misclassified and
      better correlation is achieved with putative markers of kidney disease
      progression. Masked hypertension - normotension in the clinic, hypertension at
      home - is associated with higher risk of end-stage renal disease in patients with
      chronic kidney disease. Conversely, 'white coat' hypertension - hypertension in
      the clinic and normotension at home - is associated with better renal outcomes.
      Ambulatory blood pressure monitoring is also prognostically superior to clinic
      blood pressure but does not further refine the prognosis made by home blood
      pressure monitoring. In patients on hemodialysis, home blood pressure, not
      predialysis and postdialysis blood pressure, shares the combination of high
      sensitivity and high specificity of greater than 80% to make a diagnosis of
      hypertension with the reference standard of ambulatory blood pressure monitoring.
      In addition, home blood pressure is a better correlate of left ventricular
      hypertrophy in patients on hemodialysis compared with peridialysis blood
      pressure. SUMMARY: Home blood pressure monitoring should be an essential part of
      management of hypertension in patients with all stages of chronic kidney disease.

PMID- 16609301
TI  - Asymmetric dimethylarginine: a new player in the pathogenesis of renal disease?
AB  - PURPOSE OF REVIEW: This review summarizes current knowledge on asymmetric
      dimethylarginine, renal function in health and disease, and renal disease
      progression and examines interventions that may modify the plasma concentration
      of this methylarginine. RECENT FINDINGS: Nitric oxide deficiency may occur in
      patients with chronic kidney disease and may contribute to accelerate progression
      of chronic kidney disease, hypertension and cardiovascular complications. An
      increase of endogenous nitric oxide inhibitors like asymmetric dimethylarginine
      seems to play a major role in this process. The kidneys are crucial in both, in
      re-absorbing and generating L-arginine as well as in eliminating asymmetric
      dimethylarginine primarily by the enzyme dimethylarginine dimethylaminohydrolase
      and to a minor degree by urinary excretion. Asymmetric dimethylarginine
      accumulation predicts both accelerated renal function loss and death in patients
      with chronic kidney disease and incident cardiovascular complications in patients
      with end stage renal disease. SUMMARY: Asymmetric dimethylarginine is a new risk
      factor potentially implicated in the progression of renal insufficiency and in
      the high rate of cardiovascular complications of patients with chronic kidney
      disease.

PMID- 16609302
TI  - Bibliography. Current world literature. Renal immunology and pathology.

PMID- 16609304
TI  - Nasogastric tube insertion in a child with neurodevelopmental disabilities: size
      does matter: a case study.
AB  - Many children with neurodevelopmental disabilities require a nasogastric feeding
      tube for nutrition at some point in their lives. Because of impaired cognition,
      anatomical factors, excessive drooling, hyperactive gag reflexes, or some
      medications, nasogastric tube intubation may be extremely difficult. The case
      study described here is intended to provide the reader with some suggestions for
      making feeding tube placement easier for the patient, family, and nursing staff.

PMID- 16609303
TI  - Worker safety and glutaraldehyde in the gastrointestinal lab environment.
AB  - Glutaraldehyde is considered a high-level surgical disinfectant commonly used in
      the United States in gastrointestinal lab environments. Glutaraldehyde requires
      proper ventilation when used as glutaraldehyde vapors are known irritants to the
      skin, eyes, nose, and lungs without proper ventilation in the work environment.
      Vapor concentration is the unit of measurement for the environmental presence of
      glutaraldehyde. Safe levels of glutaraldehyde vapor concentrations are a
      significant issue in the work environment. The American Conference of
      Governmental Hygienists has established and reported safe and allowable limits
      for vapor concentration of glutaraldehyde. Unfortunately, uncontrolled
      glutaraldehyde exposure in selected work environments is contributing to
      occupational asthma. Environmental exposure to glutaraldehyde has been linked to
      respiratory sensitization of the workers exposed and suggests the need for safe
      work environments anywhere glutaraldehyde is in use. Gastrointestinal labs use
      high-level disinfectants like glutaraldehyde to safely and thoroughly disinfect
      endoscopic instruments and accessories; however, there are worker-safety
      considerations relevant to glutaraldehyde use. The purpose of this article is to
      identify and describe clinical issues and challenges associated with worker
      safety and proper ventilation of glutaraldehyde in a gastrointestinal
      environment. A multidisciplinary problem-solving approach for use in
      identification and intervention for glutaraldehyde exposure and safety
      recommendations related to glutaraldehyde use as a high-level disinfectant in one
      gastroenterology lab environment will be highlighted.

PMID- 16609305
TI  - Important facts about intestinal feeding tube placement.
AB  - Enteral feeding is desirable when the gastrointestinal tract is functional
      because it allows better use of nutrients, is safer, and is more cost-effective
      than parenteral nutrition. Feeding through a gastric tube, however, is often not
      feasible in severely ill adults and children because of gastric paresis leading
      to recurrent episodes of gastroesophageal reflux with the risk of subsequent
      aspiration. Feeding into the small intestine (duodenum or jejunum) through a
      nasointestinal tube, therefore, is preferred. Unfortunately, no method of enteral
      feeding is risk free. This literature review addresses the following 10 topics:
      (a) the reasons why nasointestinal tube feeding is better tolerated by some
      patients, (b) candidates for nasointestinal tube feeding, (c) options for
      selecting nasointestinal tubes, (d) recommended methods for predicting the
      distance to insert nasointestinal tubes, (e) recommended methods for placing
      nasointestinal tubes, (f) how promotility medications work and whether they
      facilitate nasointestinal tube placement, (g) nasointestinal tube placement error
      rate, (h) methods of determining the internal location of nasointestinal tubes,
      (i) complications associated with nasointestinal tube use, and (j) other
      pertinent issues surrounding feeding through nasointestinal tubes. The available
      research evidence is summarized and recommendations for future work are
      suggested.

PMID- 16609307
TI  - Electrosurgery in the gastroenterology suite: principles, practice, and safety.
AB  - An electrosurgery generator is a critical piece of equipment in any therapeutic
      endoscopy setting. Electrosurgery uses rapidly alternating current, provided by
      the electrosurgery generator, for both therapeutic cutting and coagulation of
      tissue. Basic variables important to electricity in general are also important to
      electrosurgery: current, voltage, circuit, and impedance (resistance). Monopolar
      and bipolar accessories (electrodes) are used in the endoscopy suite and these
      terms refer to the way in which the electric circuit is completed by the flowing
      current. Impedance resists current flow and changes with tissue type and degree
      of therapeutic coagulation. Waveforms are the high-frequency output selected by
      the operator when using an electrosurgery generator. Waveforms may be continuous
      or interrupted (modulated) and differ in voltage and degree of modulation.
      Certain waveforms are typically chosen for particular applications or
      accessories, such as polypectomy with a snare, because of predictable tissue
      effect attributes of that waveform. Safe application of grounding pads, careful
      management of active accessories, and good care of electrosurgical equipment are
      crucial to patient and operator safety.

PMID- 16609309
TI  - A case of health disparity: treatment issues in women with hepatitis C.
AB  - Although the incidence of hepatitis C virus (HCV) in women is only slightly less
      than in men, women are poorly represented in research trials. As a result, not
      much is known about them as a subgroup. The specific aims of this article were to
      report on the problem, study methods, and findings focusing on HCV-positive
      women's health beliefs, how they identify and understand their health and illness
      states, and their explanatory models of illness behavior. A pilot study using
      three focus groups was conducted with women in the community, in recovery, and
      incarcerated. Two groups emerged: those with and those without access to
      knowledge and HCV services. Latinas emerged as a prominent subgroup. Women in all
      three groups wanted more information and to stay clean, were worried about
      contagion, and stated that they were secretive and ashamed of their disease. Due
      to the small study design, this study should be repeated with a larger sample and
      in a wider geographic area. The results suggest that immediate interventions for
      this health disparity are needed, including dissemination of this information to
      primary and specialty care providers and the legislature.

PMID- 16609310
TI  - Standards of infection control in reprocessing of flexible gastrointestinal
      endoscopes.

PMID- 16609311
TI  - Family member presence during procedures.

PMID- 16609312
TI  - Propofol.

PMID- 16609313
TI  - High-level disinfection.

PMID- 16609314
TI  - Medical ethics and nursing ethics: is there really any difference?

PMID- 16609315
TI  - Posture, please.

PMID- 16609316
TI  - How to start a research proposal.

PMID- 16609317
TI  - More evidence supporting colorectal cancer screening.

PMID- 16609318
TI  - Multiple sclerosis: disability profile and quality of life in an Australian
      community cohort.
AB  - The objective of this study was to determine the experience of disability and
      reported symptoms in multiple sclerosis in an Australian community sample,
      comparing the perceptions of patients, carers and treating doctors, and to
      examine effects on quality of life, carer stress and utilization of health
      services. The study design used a prospective cross sectional community survey.
      The participants were persons with a confirmed diagnosis of multiple sclerosis,
      with quantified neurological, mobility and cognitive deficits, from a tertiary
      hospital database (n=101), who lived at home, and their carers and doctors. The
      study method used demographic, diagnostic and disease severity data extracted
      from the database. Structured interviews conducted at home included: (1) open
      questionnaires for participant, carer and general practitioner, prioritizing
      symptoms/problems affecting daily living; and (2) standardized assessments for
      patient quality of life, caregiver strain and perceived burden of care. The mean
      age was 49 years (range 28-64). Those more severely affected had a significantly
      reduced quality of life and increased carer burden than those with milder
      disability, but discordance between patients, carers and doctors was noted in
      their perception of problems and symptom experience. Rates of depression (67%)
      and work-related problems were high, but vocational support was rarely provided.
      Forty persons used interferon, of whom 20 had secondary progressive multiple
      sclerosis; 39% reported difficulty in accessing rehabilitation services and only
      10% were referred to medical rehabilitation units. In conclusion, the rates of
      disability and symptom experience were similar to other series; however, access
      and utilization of appropriate rehabilitation and support services appears to be
      lacking. There were higher reported rates of depression and poor quality of life.
      Opportunities may possibly exist to re-deploy resources to develop vocational
      support, counselling and rehabilitation.

PMID- 16609319
TI  - A network-based geriatric rehabilitation programme: study design and baseline
      characteristics of the patients.
AB  - The objective of this paper is to present the design and participants of an
      ongoing randomized controlled trial on a network-based geriatric rehabilitation
      programme, targeted at frail elderly persons with progressively declining health
      and a high risk of institutionalization. Forty-one municipalities, seven
      rehabilitation centres and a total of 741 frail elderly (65+years) community
      living persons participated in the study. Assessments included measurements of
      physical capacity (balance, handgrip strength, walking speed), Functional
      Independence Measure, Geriatric Depression Scale, 15 Dimension quality of life
      questionnaire and Mini Mental State Examination. Questionnaires covered physical,
      social and psychological factors. The participants were old (mean age 78 years,
      range 65-96) and mainly female (86%). They were physically frail and most of them
      (66%) had experienced deterioration of health within 1 year. The majority lived
      alone (72%) and received regular help from other people (99%). The mean Mini
      Mental State Examination and Geriatric Depression Scale scores were 25.2 and 4.1
      points, respectively. Depressive mood (Geriatric Depression Scale>6 points) was
      found in 17% and declined cognitive function (Mini Mental State Examination<24
      points) in 28% of the participants. Differences between the randomized
      intervention and control groups were insignificant. Since the number of
      participants is sufficient statistically, the prospects for evaluating the
      effectiveness of the programme, and identifying potential benefactors, are good.

PMID- 16609320
TI  - Stroke rehabilitation outcome: the Turkish experience.
AB  - The objectives of this study were to examine the demographic and clinical
      characteristics of stroke patients admitted for inpatient rehabilitation, to
      study the occurrence of medical problems/complications, and to document
      functional outcome and possible factors influencing outcome. The mean age of this
      cohort (30 females, 53 males) was 58+/-12 years and the mean length of hospital
      stay was 45.7+/-23 days. The most common medical comorbidity was hypertension
      (65%), followed by heart disease (42%) and diabetes mellitus (22%). The length of
      hospital stay was related to the number of medical comorbidities (r=0.24,
      P<0.05). Almost all patients experienced several medical problems during
      rehabilitation stay (average 7.1 events/patient). Shoulder dysfunction (80.7%),
      symptomatic blood pressure fluctuations (72.3%) and psychosocial problems (57.8%)
      were among the most common problems. There was a statistically significant
      improvement in total Functional Independence Measure scores from admission to
      discharge (56.5 vs. 74.6), with a mean gain of 18.1. Functional Independence
      Measure gain was significantly correlated with onset to admission time (r=-0.21,
      P<0.05), length of hospital stay (r=0.50, P<0.001) and the number of previous
      strokes (r=-0.23, P<0.05), but not with age, onset to admission interval,
      comorbidities and the presence of medical problems. Discharge total Functional
      Independence Measure scores were significantly correlated only with the admission
      total Functional Independence Measure scores (r=0.72, P<0.001) and onset
      admission interval (r=-0.23, P<0.05). Significant functional improvements were
      documented in this cohort of stroke patients after an interdisciplinary
      rehabilitation approach. Discharge functional status was best correlated with
      admission functional status. Medical problems/complications were common among
      patients undergoing stroke rehabilitation. In our patients, functional outcomes
      were not significantly influenced by the occurrence of medical problems.

PMID- 16609321
TI  - Consideration of out-of-home placement among Israeli Jewish and Arab parents of
      children with disabilities.
AB  - This article is based on a secondary analysis of a random sample of 512 Israeli
      parents of children with disabilities (ages 3-17) regarding their consideration
      of out-of-home placement. Major findings showed that Arab parents reported
      greater levels of personal and family burden compared to Jewish parents. Despite
      that fact, Arab parents rarely considered out-of-home placement. In addition,
      parents whose children utilized more services reported a greater burden of care
      than those who utilized fewer services. Findings are discussed with respect to
      future research and policy implications.

PMID- 16609322
TI  - Validity and reliability of the Community Integration Program Questionnaire.
AB  - The Community Integration Program Questionnaire was developed to measure various
      quantifiable characteristics of community integration programs for people with
      brain injury. There are three versions: one for outpatient facility-based, one
      for residential and one for home programs. In this study questionnaires were
      administered to directors and associate directors of seven programs. A research
      assistant then went on-site to collect corresponding data using patient records,
      planning books and schedules, annual and quarterly reports, employee lists, staff
      curricula vitae, census data, insurance payment data, team meeting notes,
      incident reports, and staff logs. Matching criteria between questionnaire and on
      site data were established before either was collected. The survey data matched
      data acquired on-site in 42.2, 56.4, and 56.8% of questions in the three
      versions, respectively. Interviewers and a second listener recorded the same
      information 91.5% of the time across seven program interviews. For two programs,
      comparisons between a Program Director and Program Coordinator yielded matches on
      42.8 and 40.6% of questions, respectively. In conclusion, the Community
      Integration Program Questionnaire does not have acceptable construct validity and
      inter-rater reliability. Researchers requiring information about quantifiable
      characteristics of community integration programs should go on-site to collect
      the data.

PMID- 16609323
TI  - The effectiveness of a stroke education group on persons with stroke and their
      caregivers.
AB  - The educational group has been proposed as an effective way to deliver a program
      based on structured stroke knowledge to enhance emotional support among people
      with stroke and their caregivers. The aim of this study was to explore whether
      the stroke educational group could increase stroke-related knowledge, and improve
      perceived health status, in persons with stroke and their caregivers, and thus
      reduce the stress induced during the care-giving process. In this study a quasi
      experimental design, that included a pre-test and a post-test, was employed on a
      total of 54 patients with stroke and 32 caregivers who participated in a 2-week
      stroke educational group. The outcome measures included a Stroke Knowledge Test,
      the Short-Form 36 and the Relatives' Stress Scale. The tests were administrated
      before and after the running of the stroke educational group as well as, during
      the 1-week, 2-week and 1-month follow-up sessions. The results showed a
      statistically significant increase in stroke-related knowledge in the patients (F
      [1,51]=7.28-9.67, P<0.01) and their caregivers (F [1,30]=44.19-80.49, P<0.01),
      but no similar significant improvement was noted on perceived health status and
      care-giving stress. A significant association between the total scores in the
      stroke knowledge test and the admission scores in the Mini Mental State
      Examination of the patients was also revealed (F [1,51]=48.03-58.87, P<0.01). In
      conclusion, the results suggest that there was an improvement in the acquisition
      of stroke-related knowledge by both patients with stroke, and their caregivers,
      after a stroke educational group. A further study exploring the behavioral
      changes of individuals with stroke and their caregivers after attending a stroke
      educational group is recommended.

PMID- 16609324
TI  - 'We couldn't function without volunteers': volunteering with a disability, the
      perspective of not-for-profit agencies.
AB  - Volunteers play an important role in many organisations that deliver services for
      the public good. Many people within the community choose to volunteer and there
      is a rich literature on the reasons why people do so, as well as the benefits
      that accrue to individuals, organisations and the community. However, there are
      few reports of people with long-standing disability becoming volunteers. The aim
      of this study was to explore the views of volunteer coordinators in not-for
      profit organisations concerning people with long-standing disability as
      volunteers. Seven coordinators participated in two focus groups. The participants
      identified opportunities for people with a disability to contribute as
      volunteers, but were also quick to point out significant barriers. The findings
      from this exploratory study suggest that if people with long-standing disability
      are to volunteer, consideration must be given to their individual requirements
      and overcoming negative community attitudes.

PMID- 16609325
TI  - The predictive factors for length of stay for stroke patients in Taiwan using the
      path model.
AB  - The aim of this study was to examine the predictive factors, and their relative
      strengths, for predicting length of rehabilitation stay using the path model. One
      hundred and seventeen stroke patients were recruited from two rehabilitation
      units in university-affiliated hospitals in northern Taiwan. The Taiwanese
      Rehabilitation Database System was used to collect the patient's relevant
      information. Path analysis was used to explore the relative strengths of each
      predictive factor. The results showed that the ability to engage in self-care
      activities was the only direct predictor, whereas subjective well-being and
      cognitive social skills had an indirect effect on the length of rehabilitation
      stay, mediating through cognitive-social skills and ability to engage in
      activities of daily living, respectively. The effect of subjective well-being,
      mediating through cognitive-social skills, on the length of stay was about 1.5
      times that of the effects of ability to engage in self-care activities on length
      of stay. The results of the study confirmed that the ability of stroke patients
      to engage in self-care activities consistently had a major impact on the length
      of stay. The effect of subjective well-being of the patients on the
      rehabilitation outcome raised the issue of psychosocial rehabilitation as an
      important part of successful rehabilitation services.

PMID- 16609326
TI  - The effect of work on people with severe mental illness in Taiwan using a stress
      social support model: an exploratory study.
AB  - Satisfaction with quality of life is one aspect of a positive and successful
      life, and this remains true in the rehabilitation of people with severe mental
      illness. This study explores the meaning and impact of work on people with severe
      mental illness in Taiwan and, specifically, the value of encouraging people with
      severe mental illness to work to enhance their quality of life. We apply stress
      social support theory (a Western model) to examine daily life and work stressors
      in an Eastern cultural environment (Taiwan). We use multiple regression models to
      analyze predictive factors for their effect on life quality. There are five
      categories: socio-demographic characteristics, mental illness history, current
      work status variables (as controls), stress variable and social support variable.
      Unlike Western studies, current work status, in itself, did not lead to better
      satisfaction with quality of life, but the stress-social support model did. The
      implications for rehabilitation success are discussed.

PMID- 16609327
TI  - Effects of alternative communication on the communicative effectiveness of an
      individual with a progressive language disorder.
AB  - This study was designed to investigate the effects of two different modes of
      communication on the communicative output of an individual who is no longer able
      to communicate verbally, presenting with a primary progressive aphasia and
      apraxia of speech. The two treatment approaches included training the patient
      with a text-to-speech alternative communication device and with American sign
      language. An alternating treatment design was used to compare two communicative
      approaches (an alternative communication device and American sign language) on
      the subject's communicative effectiveness. Communicative effectiveness was
      measured in terms of number of words, correct information units and percentage
      correct information units, using a protocol that was adapted to quantify the
      output generated by the alternative communication device and American sign
      language. Increases across all three measures resulted for both the alternative
      communication device and American sign language. The clinical implications are
      explored, and the results add to existing studies regarding treatment
      possibilities using alternative communication for individuals who present with a
      progressive speech and language disorder, without concomitant cognitive deficits.

PMID- 16609328
TI  - Attitudes toward people with disabilities: a comparison between health care
      professionals and students.
AB  - The objective of this study was to explore the attitudes of health care
      professionals and their students towards people in Hong Kong with disabilities.
      The attitudes of four groups of professionals and students (physiotherapists,
      occupational therapists, social workers and nurses) were assessed using the well
      documented Attitude Toward Disabled Persons scale through the methodology of
      mailed questionnaires. Comparisons were made among different groups of students
      and professionals in order to gain insight into factors affecting their behavior.
      In this study, 511 students and 489 professionals were selected randomly. The
      results indicated that the overall mean Attitude Toward Disabled Persons scale
      score of the respondents was comparatively lower than that of their counterparts
      in foreign countries. The professionals had a significantly higher attitudinal
      score than the students. Among the four disciplines, nurses held the least
      favorable attitudes towards people with disabilities. In addition, their
      attitudes were less positive than those of the student nurses. On the other hand,
      the social work students had less favorable attitudes than the professional
      social workers, as well as other types of health care students. The analysis of
      the data also revealed that the mean Attitude Toward Disabled Persons scale
      scores for both the occupational therapists and occupational therapy students
      were above the overall average. Unlike the physiotherapists, the mean Attitude
      Toward Disabled Persons scale score of the physiotherapy students was below the
      overall average. In addition, age, year of study, educational level, knowledge
      and contact with people with disabilities were significant factors in the
      attitudes held by the students and professional respondents. The quality of the
      contact was found to be a dominant factor in affecting the scores on attitude.
      Thus, recommendations were made to modify the current training curriculum and
      enhance the quality of services to develop more favorable attitudes towards
      people with disabilities.

PMID- 16609329
TI  - Special education teachers' perceptions of factors influencing their
      instructional practices.
AB  - The study examined the variables associated with the effective instructional
      practices of teachers of students with learning disabilities. Subjects were 146
      female special education teachers, working in the special education classroom.
      Demographic information was gathered from all participants (e.g. years of
      experience, collaboration in school and job satisfaction). Participants responded
      to a 63-item questionnaire about effective instructional practices. The
      questionnaire consisted of four sub-scales (i.e. planning instruction, managing
      instruction, delivering instruction and evaluating instruction). In general, the
      effectiveness of instructional practices of teachers was moderate (mean=2.08,
      SD=0.55). No significant correlation was found between years of experience and
      effective instructional practice or between collaboration and effective
      instructional practices. A significant correlation was, however, found between
      job satisfaction and effective instructional practices.

PMID- 16609330
TI  - Survey of general practitioners' attitudes toward physical medicine and
      rehabilitation.
AB  - This study reports the attitudes of general practitioners towards physical
      medicine and rehabilitation after participating in a continued medical education
      course in this field. Given the high prevalence of musculoskeletal disorders and
      number of disabled persons in the country, along with the role of general
      practitioners in the primary and long-term management of such patients, basic
      competency in rehabilitation medicine must be considered in the educational
      curriculum of medical students. Nevertheless, rehabilitation medicine is not
      taught in most universities. This study was performed to evaluate the attitude of
      general practitioners towards physical medicine and rehabilitation as a baseline
      for developing educational programs in this field. In a simple descriptive study,
      at the end of a continued medical education program in low back pain management,
      217 questionnaires, focusing on the field of physical medicine and
      rehabilitation, were distributed between participants. One-hundred-and-forty
      three questionnaires were analyzed. Statistical analyses were performed with
      descriptive and Student's t-test. The results showed that of the participants, 69
      (48.3%) were female and that they graduated from 24 medical schools. Most
      respondents (92.2%) believed that musculoskeletal education had not been
      sufficient in general practitioner training courses. Of the respondents, 56.8%
      had visited at least one disabled patient during the previous month, while 11%
      had visited more than 10 in the same period, but 84.3% had not studied
      disabilities. Musculoskeletal physical examination was the most needed
      educational field cited by general practitioners. In conclusion, this study
      clearly documents the inadequacy of basic rehabilitation training in medical
      schools. The findings reveal the most needed and preferred rehabilitation areas
      for general practitioners, and these should be considered in the establishment of
      rehabilitation training programs for Iranian medical students.

PMID- 16609331
TI  - Music: a strategy to promote health in rehabilitation? An evaluation of
      participation in a 'music and health promotion project'.
AB  - This study illuminates the role and significance of music listening in everyday
      life for the long-term ill. Twenty-two participants, aged 34-65 from Oslo and
      Akershus in Norway, were recruited as a strategic sample and took part in eight
      in-depth interviews over a 1-year period, from 2004 to 2005. Four double CD
      compilations from different genres, part of the project, were used as devices to
      discover whether participants could learn to use music as a 'technology' for self
      help, with regard to health, healing and recovery, through exposure to and
      exchange of new musical materials and practices. A novel Participatory CD design
      was developed, and the beneficial experiences of taking part in the project
      resulted in an increase in self-awareness and self-consciousness. Listening to
      and discussing music was considered to be an important tool in the process of
      change, sense of agency and self-development, through enhancing well-being and
      'wellness', a vital factor in the process of recovery and sustaining quality of
      life, despite of illness.

PMID- 16609332
TI  - Sibling advocates of people with intellectual disabilities.
AB  - The aim of this study was to examine the experience of the first generation of
      sibling advocates in Hong Kong. A qualitative approach was adopted and six
      sibling advocates of people with intellectual disabilities from one non
      government organization were interviewed. Data were analyzed using a constant
      comparative method and content analysis. Findings revealed that the six
      participants were reactive in the process of taking up the caregiver
      responsibility and they performed three functions: to advocate for more service
      provision, to improve service quality, and to facilitate communication between
      individual service units and family members of people with intellectual
      disabilities. All of the participants expressed that they needed support from
      service providers when they tried to function as the sibling advocates.
      Strategies to promote the involvement of siblings of people with intellectual
      disabilities as advocates are discussed and it is expected that more siblings of
      people with intellectual disabilities will be supported to have a higher level of
      involvement in advocacy.

PMID- 16609333
TI  - Drooling in children with cerebral palsy: a qualitative method to evaluate
      parental perceptions of its impact on daily life, social interaction, and self
      esteem.
AB  - Research on the treatment of drooling applies measures such as salivary flow
      rate, qualitative observations of drooling severity in standardized situations,
      and anecdotal or one-dimensional parental and teacher reports. To assess drooling
      severity in a range of everyday conditions, and its impact on the daily life of
      children and their families, two parent questionnaires were constructed. Results
      of baseline measurements of 43 children with cerebral palsy showed that the
      questionnaires measured the variation in drooling severity across daily life
      conditions, and enabled evaluation of the impact of drooling on the ability to
      eat, drink and speak, on daily care, economic consequences, and social
      interactions. The section on the impact of drooling on self-esteem appeared not
      to be fully applicable for non-speaking children with a low developmental status.
      The questionnaires offer a qualitative method to evaluate parental perceptions of
      the impact of drooling and evaluate the effectiveness of interventions to reduce
      drooling.

PMID- 16609334
TI  - Nursing cooperative partnership: a recruitment benefit.

PMID- 16609335
TI  - Re-igniting the Spirit.

PMID- 16609336
TI  - Retention strategies for newly hired Filipino nurses.

PMID- 16609338
TI  - E-bidding and hospital agency usage.

PMID- 16609339
TI  - Nursing administration in Russia.

PMID- 16609340
TI  - Nursing intensity billing.
AB  - Hospital nursing care has traditionally been billed using a fixed daily room and
      board rate. This approach hides the variability of nursing care within and across
      nursing units and does not align nursing costs with daily charges for actual
      patient care. Anew nursing intensity billing (NIB) model for assigning hospital
      daily room charges is proposed, and initial results are reported. METHODS: Two
      charge methods, one using traditional room and board daily billing and another
      using an NIB approach, were developed for 12 adult medical or surgical units at
      the Medical University of South Carolina (MUSC) Medical Center using
      retrospective data from January 1 to May 31, 2005. The room and board charge was
      assigned as private room or intermediate care based primarily on patient
      location. The NIB model added an additional focused care charge between private
      and intermediate care, and the charge for the 3 levels was based on daily nursing
      intensity entered as actual hours of nursing care delivered. The mean and sum of
      charges were compared between the 2 methods. Charge rates were simulated at $700,
      $950, and $1,200 for the 3 levels, which correlated with the existing proprietary
      room rates. Nursing cost-to-charge ratios were calculated for room and board and
      NIB methods. RESULTS: The NIB model resulted in a 32.2% increase in charges or a
      total sum of $4,870,250 for the 12 nursing units over the 5-month period. The
      variability of nursing cost-to-charge ratio was reduced from 0.34 to 0.80 for
      room and board to 0.33 to 0.45 for the NIB method. CONCLUSION: The NIB method of
      assigning charges based on nursing intensity rather than on patient location
      increased overall charges and more evenly distributed direct nursing costs to
      daily charges. Assigning charges based on nursing intensity is appealing as it
      reflects actual care given in the acute care environment. The NIB provides
      evidence to support higher charge rates and has the ability to redistribute
      hospital charges based on nursing care. The relationship between increased daily
      hospital charges and actual reimbursement is unknown.

PMID- 16609341
TI  - Beyond the BARRIERS Scale: commonly reported barriers to research use.
AB  - The evidence-based practice movement has highlighted the importance of
      translating research evidence into practice. However, the gap between research
      and practice points to the existence of significant barriers to research use. To
      identify the most commonly cited barriers to the use of research in practice, the
      findings arising from studies that used the Barriers to Research Utilization
      Scale are examined. Based on these findings, the authors discuss and make
      recommendations to assist nurse administrators in overcoming universally reported
      barriers to research use.

PMID- 16609342
TI  - Framing patient safety initiatives: working model and case example.
AB  - The authors describe an original patient Safety Platform Model. The model
      identifies the broad components involved in patient safety initiatives and
      outlines their relationship to one another. A case example of how the model can
      be used is given as the authors describe a falls-prevention program.

PMID- 16609343
TI  - Inactive nurses: a source for alleviating the nursing shortage?
AB  - OBJECTIVE: This study seeks to provide an understanding of why inactive
      registered nurses chose to become inactive and what they would require for them
      to return to nursing. BACKGROUND: In 2000, a shortage of 110,000 (6%) registered
      nurses existed in the United States. If the current trends continue, the shortage
      is projected to grow to 29% by 2020. One solution to the nursing shortage may be
      attracting nurses with inactive licenses back into employment. METHODS: This
      study used a quantitative, cross-sectional survey design. Data analysis included
      descriptive and inferential statistics. RESULTS: Inactive nurses (N = 428)
      younger than 60 years in 1 Southern state were surveyed. A major portion (27.6%)
      of these nurses left nursing because of a conflict between parenting duties and
      scheduling requirements (13.5%) at work and indicated that they would return to
      nursing if given the opportunity to work part-time, especially if shifts were
      flexible and shorter. CONCLUSION: Although the group of registered nurses younger
      than 60 years do not constitute a large percentage of nurses in this country,
      they are a potential source of alleviating, to some extent, the critical nursing
      shortage. Employers can encourage many of these nurses to return to work by
      providing more flexible work schedules, including part-time and shorter shifts,
      as well as decreased workloads.

PMID- 16609344
TI  - The slippery slope: differentiating between quality improvement and research.
AB  - As hospitals strive to create strong work environments for nurses, many use the
      core requirements for Magnet designation to enhance and build new programs in
      research and evidence-based practice into patient care and operational processes.
      The problem is the use of quality improvement projects in these efforts as
      evidence of a healthy "research" program. This confusion can lead to 3 major
      consequences: (1) poorly designed and interpreted studies; (2) lack of
      consideration of subject rights; and (3) Institutional Review Board or other
      regulatory sanctions for noncompliance with federal, state, and local law and
      institutional policies. The purpose of this article is to differentiate between
      research and quality improvement, explore the potential risks of confusing
      quality improvement with research, and suggest criteria by which to determine the
      difference.

PMID- 16609345
TI  - Prolongation of the cardiac QTc interval in Turner syndrome.
AB  - Anatomic anomalies of the cardiovascular system occur in approximately 50% of
      individuals with Turner syndrome (TS), with the specific genetic cause(s) for the
      heart defects still unknown. Because congenital heart disease may be associated
      with conduction system abnormalities, we compared electrocardiograms (ECGs) in
      100 women with TS and 100 age-matched female controls. Women with TS were
      significantly more likely to demonstrate left posterior fascicular block (p <
      0.005), accelerated AV conduction (p < 0.006), and T wave abnormalities (p <
      0.006). The PR interval was significantly shorter (137 +/- 17 vs. 158 +/- 18 ms,
      p < 0.0001) and the rate-corrected QT interval (QTc) significantly longer in
      women with TS than in controls (423 +/- 19 ms vs. 397 +/- 18 ms; p < 0.0001).
      Twenty-one women with TS but no controls had a QTc greater than 440 ms. We found
      no statistically significant relation between body habitus, cardiac dimensions,
      evidence of congenital heart disease, or metabolic parameters and the incidence
      of ECG abnormalities or QTc duration in TS. Cardiac conduction and repolarization
      abnormalities appear to be intrinsic features of TS, suggesting that deletion of
      the second sex chromosome has more profound effects on the cardiovascular system
      than previously recognized, and that ECG analysis should be included in
      evaluating and monitoring patients with Turner syndrome.

PMID- 16609346
TI  - Statin-associated myasthenia gravis: report of 4 cases and review of the
      literature.
AB  - A few recent individual case reports have suggested that a myasthenic syndrome
      may be associated with statin treatment, but this association is not well
      described. We report 4 patients who developed symptoms of myasthenia gravis
      within 2 weeks of starting treatment with a statin drug. In 1 case the drug
      appears to have exacerbated underlying myasthenic weakness, whereas in the other
      3 cases, de novo antibody formation appears to be most likely. In each case, some
      degree of recovery followed discontinuation of the statin medication.

PMID- 16609347
TI  - Culture-positive and culture-negative endocarditis in patients with cancer: a
      retrospective observational study, 1994-2004.
AB  - Endocarditis is uncommon in patients with cancer. The characteristics of culture
      positive (CPE) and culture-negative endocarditis (CNE) in high-risk cancer
      patients are not known; therefore we sought to evaluate the disease
      characteristics in patients with endocarditis at a comprehensive cancer center.
      We retrospectively reviewed the transthoracic (TTE) and transesophageal (TEE)
      echocardiograms obtained from 654 consecutive cancer patients in whom
      endocarditis was suspected between 1994 and 2004. Endocarditis was confirmed in
      45 (7%) of 654 patients using modified Duke University criteria based on
      information obtained from hospital records and computerized data systems. In 21
      (95%) of 22 cases, TEE examinations were diagnostic, and 16 (42%) of 38 patients
      with initially nondiagnostic TTE studies had the diagnosis confirmed by TEE
      study; this difference between diagnostic TEE and initial nondiagnostic TTE was
      significant (p < 0.0001). Among the 26 (58%) patients with CPE, Staphylococcus
      aureus (35%) was the most common organism isolated, followed by coagulase
      negative Staphylococcus species (23%). Eighteen (78%) of 23 patients with a
      central venous catheter had CPE, whereas only 8 (36%) of 22 patients without a
      central venous catheter had CPE (odds ratio [OR], 6.3; 95% confidence interval
      [CI], 1.69-23.53; p < 0.006). Vegetations were larger in patients with CPE than
      in patients with CNE (median +/- standard deviation, 10 +/- 8.8 vs. 8.7 +/- 3.9
      mm). Fifteen patients (58%) with CPE and 10 (53%) with CNE had embolic
      complications. We note that cutaneous and septic pulmonary emboli were more
      common in patients with CPE than in patients with CNE (31% vs. 11% and 15% vs.
      0%, respectively), whereas embolic cerebrovascular and fatal embolic coronary
      events were more common in patients with CNE than in those with CPE (37% vs. 12%
      and 21% vs. 0%, respectively; p = 0.026). The 4-week endocarditis-attributable
      death rate did not differ significantly between the groups (CPE, 15% vs. CNE,
      32%; p = 0.28). On stepwise multivariate regression analysis, patients with
      neutropenia (OR, 22.52; 95% CI, 2.25-225.48; p < 0.008) and those with embolic
      cerebrovascular events (OR, 17.07; 95% CI, 1.63-178.45; p < 0.01) had an
      increased probability of death due to endocarditis. The clinical spectrums of CPE
      and CNE differed in these patients with cancer. In patients with CNE, embolic
      cerebrovascular and fatal myocardial infarction were relatively common.

PMID- 16609348
TI  - Vasculitis in systemic lupus erythematosus: prevalence and clinical
      characteristics in 670 patients.
AB  - We conducted the current study to determine the prevalence and clinical
      characteristics of vasculitis in a large series of patients with systemic lupus
      erythematosus (SLE), focusing on the classification and clinical significance of
      the different types of vasculitis. We studied 670 consecutive patients who
      fulfilled 4 or more of the 1997 revised criteria for SLE. Definite vasculitis was
      diagnosed histologically and/or by arteriography, and probable vasculitis was
      diagnosed clinically when there were characteristic cutaneous lesions.
      Vasculitides were categorized according to the definitions adopted by the Chapel
      Hill Consensus Conference. Seventy-six (11%) patients with SLE had vasculitis (68
      female patients and 8 male; mean age, 37.8 yr); only 32 (42%) fulfilled the
      Chapel Hill definitions. Cutaneous lesions were the main clinical presentation of
      vasculitis, present in 68 (89%) patients, while the remaining 8 (11%) had
      isolated visceral vasculitis. Compared with SLE patients without vasculitis,
      patients with vasculitis had a higher prevalence of livedo reticularis (22% vs.
      3%; p = 0.028); a higher mean European Consensus Lupus Activity Measurement
      (ECLAM) score (5.86 vs. 3.87; p < 0.001); and a higher frequency of anemia (62%
      vs. 17%; p < 0.001), erythrocyte sedimentation rate (ESR) >50 mm/h (60% vs. 15%;
      p < 0.001), and anti-La/SS-B antibodies (19% vs. 5%; p = 0.014) in the
      multivariate analysis. With respect to the size of the vessels involved, 65 (86%)
      patients had small vessel vasculitis (SVV) and 11 (14%) had medium-sized vessel
      vasculitis (MVV). SLE patients with MVV had a higher prevalence of mononeuritis
      multiplex (54% vs. 2%; p < 0.001), visceral vasculitis (100% vs. 5%; p < 0.001),
      and ulcerated/ischemic cutaneous lesions (36% vs. 11%; p = 0.047) and a higher
      percentage of surgical interventions (45% vs. 0%; p < 0.001) compared with
      patients with SVV. In conclusion, we observed a heterogeneous presentation of
      vasculitides arising in the setting of SLE, with nearly 60% of cases not
      fulfilling the names and definitions adopted by the Chapel Hill Consensus
      Conference. SVV was the most frequent vasculitis, overwhelmingly cutaneous and
      clearly differentiated from MVV, which was less frequent but had predominantly
      visceral involvement (especially of the peripheral nerves). The presence of
      vasculitis in our patients with SLE was associated with a higher ECLAM score,
      livedo reticularis, hematologic parameters (anemia, high ESR), and anti-La/SS-B
      antibodies.

PMID- 16609349
TI  - Rectus sheath hematoma: review of 126 cases at a single institution.
AB  - Rectus sheath hematoma (RSH) is an uncommon condition characterized by abdominal
      pain and an abdominal wall mass. We reviewed the clinical features, treatment,
      and outcomes of 126 patients treated for RSH at Mayo Clinic from January 1, 1992,
      to December 31, 2002. Most patients (64%) were women and the mean +/- SD age was
      67.9 +/- 16.5 years. Most patients (69%) were on some form of anticoagulation
      therapy. The mean international normalized ratio was 2.6 +/- 2.4, and mean
      activated partial thromboplastin time was 64.2 +/- 42.7 seconds. No patients were
      pregnant or had a peritoneal dialysis catheter at the time of diagnosis.
      Approximately half of the patients (48%) had nonsurgical abdominal trauma around
      the time of diagnosis, with 37 patients (29%) having a cough. The most common
      presenting signs and symptoms were abdominal pain (84%) and an abdominal wall
      mass (63%). CT of the abdomen and pelvis was the most commonly used method to
      establish the diagnosis (83%). Most patients (86%) were successfully treated with
      symptom management and blood transfusion. Ten patients (7.9%) underwent surgery
      or endovascular embolization of bleeding vessels, and 2 patients (1.6%) died as a
      result of RSH bleeding. Although RSH is rarely fatal, the clinician should be
      aware of important risk factors that lead to RSH including female sex, older age,
      anticoagulation therapy, and cough or other abdominal trauma. Rapid diagnosis
      with directed history, physical examination, and CT of the abdomen and pelvis may
      help decrease unnecessary laparotomy and lead to better triage of patients who
      present with RSH.

PMID- 16609351
TI  - Is it time to incorporate quantitative functional imaging data, FDG PET in
      particular, into the response evaluation criteria in solid tumours?

PMID- 16609350
TI  - Immunogenetic risk and protective factors for the idiopathic inflammatory
      myopathies: distinct HLA-A, -B, -Cw, -DRB1, and -DQA1 allelic profiles
      distinguish European American patients with different myositis autoantibodies.
AB  - The idiopathic inflammatory myopathies (IIM) are systemic connective tissue
      diseases defined by chronic muscle inflammation and weakness associated with
      autoimmunity. We have performed low to high resolution molecular typing to assess
      the genetic variability of major histocompatibility complex loci (HLA-A, -B, -Cw,
      -DRB1, and -DQA1) in a large population of European American patients with IIM (n
      = 571) representing the major myositis autoantibody groups. We established that
      alleles of the 8.1 ancestral haplotype (8.1 AH) are important risk factors for
      the development of IIM in patients producing anti-synthetase/anti-Jo-1, -La, 
      PM/Scl, and -Ro autoantibodies. Moreover, a random forests classification
      analysis suggested that 8.1 AH-associated alleles B*0801 and DRB1*0301 are the
      principal HLA risk markers. In addition, we have identified several novel HLA
      susceptibility factors associated distinctively with particular myositis-specific
      (MSA) and myositis-associated autoantibody (MAA) groups of the IIM. IIM patients
      with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies have a unique HLA
      Class I risk allele, Cw*0304 (pcorr = 0.046), and lack the 8.1 AH markers
      associated with other anti-synthetase autoantibodies (for example, anti-Jo-1 and
      anti-PL-12). In addition, HLA-B*5001 and DQA1*0104 are novel potential risk
      factors among anti-signal recognition particle autoantibody-positive IIM patients
      (pcorr = 0.024 and p = 0.010, respectively). Among those patients with MAA, HLA
      DRB1*11 and DQA1*06 alleles were identified as risk factors for myositis patients
      with anti-Ku (pcorr = 0.041) and anti-La (pcorr = 0.023) autoantibodies,
      respectively. Amino acid sequence analysis of the HLA DRB1 third hypervariable
      region identified a consensus motif, 70D (hydrophilic)/71R (basic)/74A
      (hydrophobic), conferring protection among patients producing anti
      synthetase/anti-Jo-1 and -PM/Scl autoantibodies. Together, these data demonstrate
      that HLA signatures, comprising both risk and protective alleles or motifs,
      distinguish IIM patients with different myositis autoantibodies and may have
      diagnostic and pathogenic implications. Variations in associated polymorphisms
      for these immune response genes may reflect divergent pathogenic mechanisms
      and/or responses to unique environmental triggers in different groups of subjects
      resulting in the heterogeneous syndromes of the IIM.

PMID- 16609352
TI  - A new computer-based decision-support system for the interpretation of bone
      scans.
AB  - OBJECTIVE: To develop a completely automated method, based on image processing
      techniques and artificial neural networks, for the interpretation of bone scans
      regarding the presence or absence of metastases. METHODS: A total of 200
      patients, all of whom had the diagnosis of breast or prostate cancer and had
      undergone bone scintigraphy, were studied retrospectively. Whole-body images,
      anterior and posterior, were obtained after injection of 99mTc-methylene
      diphosphonate. The study material was randomly divided into a training group and
      a test group, with 100 patients in each group. The training group was used in the
      process of developing the image analysis techniques and to train the artificial
      neural networks. The test group was used to evaluate the automated method. The
      image processing techniques included algorithms for segmentation of the head,
      chest, spine, pelvis and bladder, automatic thresholding and detection of hot
      spots. Fourteen features from each examination were used as input to artificial
      neural networks trained to classify the images. The interpretations by an
      experienced physician were used as the 'gold standard'. RESULTS: The automated
      method correctly identified 28 of the 31 patients with metastases in the test
      group, i.e., a sensitivity of 90%. A false positive classification of metastases
      was made in 18 of the 69 patients not classified as having metastases by the
      experienced physician, resulting in a specificity of 74%. CONCLUSION: A
      completely automated method can be used to detect metastases in bone scans.
      Future developments in this field may lead to clinically valuable decision
      support tools.

PMID- 16609353
TI  - Left ventricular ejection fraction and volumes on rest gated 201Tl perfusion
      SPECT: comparison with two-dimensional echocardiography.
AB  - BACKGROUND: Rest gated 201Tl images are considered to be of poor count statistics
      due to lower energy and low photon flux of 201Tl in addition to increased
      attenuation and low dose that can be administered. We compared the left
      ventricular ejection fraction (LVEF), end diastolic (EDV) and end systolic volume
      (ESV) obtained on 4 h gated rest 201Tl myocardial perfusion single photon
      emission computed tomography (SPECT) with those obtained by two-dimensional
      echocardiography (2-D ECHO) in patients with known or suspected coronary artery
      disease (CAD). METHODS: Eighty-two consecutive patients who underwent gated 201Tl
      stress-rest myocardial perfusion SPECT and 2-D ECHO were studied. The gated
      thallium images were processed with Siemens e-soft autocardiac processor and
      LVEF, EDV and ESV were evaluated using Emory Cardiac Toolbox. The same parameters
      were also assessed on the 2-D ECHO using the modified Simpson method for
      comparison. RESULTS: Out of 82 rest gated images, one study was excluded because
      of poor count statistics. In 81 (99%) patients there was good linear correlation
      with 2-D ECHO values and rest gated 201Tl SPECT images for EDV, ESV and LVEF.
      Pearson's correlation co-efficient (r value) for EDV, ESV and LVEF between the
      two methods was 0.78, 0.79 and 0.88, respectively. A Bland-Altman plot showed
      close agreement with LVEF but not for EDV and ESV. CONCLUSION: These results
      suggest that the 4 h rest gated 201Tl study gives a reliable value for the LVEF
      compared to 2-D ECHO and can be used in routine clinical practice.

PMID- 16609354
TI  - Comparison of gastric emptying scintigraphy based on the geometric mean of the
      gastric proportion of the abdominal radioactivity or on the geometric mean of the
      intragastric radioactivity.
AB  - PURPOSE: Using gastric emptying scintigraphy the gastric retention rate is
      commonly calculated within a gastric region of interest (intragastric method).
      This technique may have significant limitations when left oblique anterior views
      are acquired, due in part to attenuation resulting from intragastric
      redistribution. To minimize these drawbacks, it was proposed to express the
      intragastric content as a percentage of the abdominal radioactivity (abdominal
      method). Our goal was to compare these two methods when anterior-posterior
      scanning is used. METHODS: Antero-posterior scintigraphic data of 272 consecutive
      patients were analysed by both methods. Retention rates were obtained by both
      observation and calculation by power exponential fit. Gastric emptying parameters
      (half-emptying time of solids (T(50,S)) and liquids (T(50,L)), lag phase (T(lag))
      time and real emptying time (T(RE))), and quality of fit were also computed and
      compared. RESULTS: For solids, the intragastric method resulted in weakly higher
      experimental retention rates, whereas retention rates were quite similar for
      liquids. Differences between experimental and calculated retention rates were
      smaller for abdominal method, for both liquids and solids. As a result, values
      for the quality of fit were higher for the abdominal method. Significant
      differences were observed only for calculated T(50,S) (122+/-46 min vs. 124+/-48
      min, mean difference 2+/-2 min, P<0.00001) and T(RE) (163+/-64 min vs. 168+/-68
      min, mean difference 4.5+/-3.8 min, P<0.05), respectively, for the abdominal and
      the intragastric methods. However, the Bland-Altman statistical method revealed
      good agreements (<5% outliers). CONCLUSION: Intragastric and abdominal methods
      can be used indifferently to treat antero-posterior data of gastric scintigraphy.

PMID- 16609355
TI  - A study of the possibility of curing Graves' disease based on the desired
      reduction of thyroid mass (volume) as a consequence of 131I therapy: a
      speculative paper.
AB  - PURPOSE: The possibility of predicting the final volume of Graves' disease
      thyroids submitted to 131I therapy could allow the physician to decide what
      activity to administer based on the desired volume reduction instead of on a
      fixed value of the thyroid radiation absorbed dose. In this paper the
      relationship between maximum uptake of 131I, fractional reduction of thyroid
      volume and outcome of Graves' disease is discussed. METHODS: The results are
      based on ultrasonography thyroid volume measurements before administration of
      therapy and at the moment of recovery from Graves' disease (thyroid stimulating
      hormone >0.3 microIU x ml(-1) in the absence of anti-thyroid drug therapy) and on
      measurements of 131I uptake in 40 patients. It is shown that the possibility of
      curing Graves' disease may be individually related to the final volume of the
      patient's thyroid. An equation is presented to calculate the 'optimal' final
      thyroid volume. RESULTS: A comparison between the traditional method, based on
      absorbed dose, and the final method, based on volume, has been carried out
      retrospectively. In the first case a median activity of 529 MBq has been
      administered; in the second, a median activity of 394 MBq (non-parametric
      Wilcoxon test, P<0.05) should be administered. The corresponding thyroid median
      absorbed doses are, respectively, 353 Gy and 320 Gy (non-parametric Wilcoxon
      test, P<0.02). CONCLUSION: A method to evaluate individually the 'optimal' final
      thyroid mass is presented and discussed. The method based on 'volume reduction'
      could probably reduce the activity and the thyroid absorbed dose compared to the
      method based on 'empirical' calculations, thus allowing the administration of
      131I therapy to be optimized.

PMID- 16609356
TI  - Effects of gender and age on the quantitative parameters of [99mTc]pertechnetate
      salivary gland scintigraphy in normal subjects.
AB  - AIM: To assess the effect of gender and age on [99mTc]pertechnetate salivary
      gland scintigraphy (SGS) in healthy subjects. METHODS: The study population
      consisted of 93 normal subjects (46 women, 47 men; age range 20-59 years). The
      subjects were categorized into eight (four female and four male) subgroups
      according to age decades. Dynamic SGS was performed after intravenous injection
      of 370 MBq [99mTc]pertechnetate. Anterior salivary gland images were acquired for
      30 min. On the basis of the time-activity curves, three functional parameters
      were calculated for the parotid and submandibular salivary glands: (1) the first
      minute uptake ratio, (2) the maximum uptake ratio, and (3) the maximum secretion
      percentage. RESULTS: For women, all parotid and submandibular functional
      parameters had a peak in the fourth decade group. The comparison of four age
      groups in the female subjects showed significant differences, except for the
      third versus the fifth decades, at least for one parameter. The number of
      significant differences was highest in the comparison between the second versus
      the fourth decades. Among men, the highest values for all parotid and
      submandibular parameters were in the second decade, except for the first minute
      uptake ratio in the submandibular gland. The number of parameters that were
      significantly different among the four age groups in men was lower than in women.
      The first minute uptake ratio of the submandibular gland had the most significant
      differences among the groups of male subjects. CONCLUSION: Age and gender
      differences have a significant effect on salivary gland functions which is more
      apparent in women than in men.

PMID- 16609357
TI  - The effect on radiochemical purity of modifications to the method of preparation
      and dilution of 99mTc-sestamibi.
AB  - BACKGROUND: 99mTc-sestamibi is a useful radiopharmaceutical for myocardial
      perfusion imaging, parathyroid imaging and breast tumour imaging. However, the
      preparation is time consuming and the limit of 3 ml on the volume of liquid that
      can be added to the Cardiolite kit vial means that it is often difficult to draw
      up small doses for patient studies. AIM: To modify the method of preparation of
      99mTc-sestamibi in order to reduce the preparation time and to give a preparation
      which is more convenient for withdrawing patient doses. METHOD: A modified kit
      was prepared by reconstituting a Cardiolite kit vial with 3 ml Sodium Chloride
      Injection (0.9%) BP, sub-dividing it into two separate nitrogen-filled vials
      before adding sodium pertechnetate and boiling for radiolabelling. 99mTc
      sestamibi was also prepared according to the manufacturer's recommended method
      and diluted with sodium chloride injection after preparation. Radiochemical
      purity was assessed by thin-layer chromatography and high-performance liquid
      chromatography. RESULTS: 99mTc-sestamibi prepared according to the manufacturer's
      recommended method had high radiochemical purity (96.9%+/-1.1%) and retained >90%
      radiochemical purity over 8 h following dilution. However, 99mTc-sestamibi
      prepared by the modified method gave variable and inconsistent results.
      CONCLUSION: The modified method of preparation was not robust enough to give
      reproducibly high radiochemical purity. However, dilution of 99mTc-sestamibi
      prepared according to the manufacturer's recommended method was satisfactory.
      This study highlights problems with the analysis of 99mTc-sestamibi and the
      limitations of modifying the method of preparation.

PMID- 16609358
TI  - Novel preparation and characterization of a trastuzumab-streptavidin conjugate
      for pre-targeted radionuclide therapy.
AB  - INTRODUCTION: This study describes a novel and convenient route for the
      preparation of a trastuzumab-streptavidin conjugate such as might be used in a
      pre-targeting system and its in-vitro and in-vivo evaluation. METHODS:
      Trastuzumab was irradiated with UV light in the presence of stannous ions to
      reduce a number of the disulfide bridges to free thiol groups. A range of
      irradiation times were studied in order to quantify the number of thiols produced
      and to optimize the reduction process. The conjugate was then prepared by
      reaction with succinimidyl 4-(N-maleimidomethy cyclohexane)-1-carboxylate (SMCC)
      linked streptavidin. RESULTS: Initial conjugation reactions in phosphate buffer
      were inefficient, producing low conjugate yields, but conjugation reactions in
      triethanolamine-based buffer showed greatly increased conjugation yields. A high
      purity product (approximately 100%) was obtained following purification by gel
      filtration HPLC as determined by subsequent size exclusion HPLC analysis. The
      conjugate was shown to possess an essentially identical immunoreactivity to that
      of the native, unconjugated antibody and an unaltered biotin binding
      stoichiometry. Shedding and internalization by Her-2-expressing cells were low
      and the uptake in vivo by Her-2-expressing xenografts in nude mice was similar to
      that of labelled antibody. CONCLUSION: Our results demonstrate a new, simple and
      effective method for the successful synthesis of antibody-streptavidin conjugates
      which could also be applied to many other heterodimeric protein conjugation
      reactions.

PMID- 16609359
TI  - Preparation of 99mTc sestamibi for parathyroid imaging.

PMID- 16609361
TI  - Polymorphisms in the human glutathione transferase zeta promoter.
AB  - OBJECTIVES: The zeta-class glutathione transferase GSTZ1-1 catalyses the
      glutathione-dependent isomerization of maleylacetoacetate to fumarylacetoacetate
      in the tyrosine catabolic pathway and the biotransformation of alpha-halo acids,
      including dichloroacetic acid (DCA). Genetic polymorphisms in the coding sequence
      of GSTZ1 result in significant changes in enzyme function, and deficiency of
      GSTZ1-1 in mice causes induction of a range of Phase-II enzymes. In this study,
      the potential for polymorphisms in regulatory sequences to alter gene
      transcription was investigated. METHODS: A total of 10 single-nucleotide
      polymorphisms (SNP) were identified in African and Australian European subjects
      in a region extending 1.5-kb upstream of the GSTZ1 start of transcription. These
      SNPs formed at least 10 haplotypes and only two were shared between the two
      population samples. The effect of these SNPs on gene expression was evaluated by
      the transient expression of specific alleles fused to a luciferase reporter gene.
      RESULTS: Of the 10 SNPs identified, only -1002 G>A and -289 C>T caused
      significant changes in promoter activity. The -1002 G>A SNP converts a v-Myb site
      to a S8 homeodomain (Prx2) site, and the -289 C>T SNP abolishes an Egr1 binding
      site. CONCLUSION: These SNPs may alter GSTZ1 expression, which may alter the
      pharmacokinetics of DCA, which is used therapeutically for the treatment of
      lactic acidosis.

PMID- 16609362
TI  - Functional single nucleotide polymorphism haplotypes in the human equilibrative
      nucleoside transporter 1.
AB  - The human equilibrative nucleoside transporter 1 gene (hENT1) is the primary
      nucleoside transporter for cytosine arabinoside (AraC), a deoxycytidine analog
      used for treatment of acute leukemias and lymphomas. We screened approximately
      1.6 kb upstream of the transcription initiation site of hENT1 for single
      nucleotide polymorphisms (SNPs) that affect gene expression. We identified one
      SNP at position -706G>C with a frequency of 21% in whites and 5% in African
      Americans. In African-Americans, we observed two SNPs at positions -1345C>G and 
      1050G>A with allele frequencies of 8% and 19%, respectively. TRANSFAC analysis
      suggested that -1345C>G and -706G>C may alter transcription factor binding sites.
      Four naturally occurring haplotypes (CGG, CAG, CGC and GAG) were cloned into a
      luciferase expression plasmid, transfected into Cos-1 cells, and reporter
      activity measured at 24 and 48 h. Three haplotypes, CAG, CGC and GAG,
      respectively, showed average expression that was approximately two-fold (P<0.05),
      1.4-fold (P<0.05) and 1.1-fold (P>0.05) higher than lowest expression haplotype
      CGG at 48 h. When reanalysed as single SNPs, the differences in expression were
      significant for -1345C>G and -1050G>A genotypes, and not for -706G>C. However,
      the magnitude of difference was reduced, suggesting that no single SNP completely
      accounts for the expression differences observed at the haplotype level. By real
      time quantitative reverse transcriptase-polymerase chain reaction assay,
      individuals with CGG/CGC haplotypes showed 1.37-fold higher median expression of
      hENT1 transcript than those with common CGG/CGG haplotypes. Although not
      statistically significant (P=0.12), this difference is in the direction predicted
      by the in vitro data. hENT1 promoter region haplotypes may influence gene
      expression and alter AraC chemosensitivity.

PMID- 16609363
TI  - Relationship between hyperbilirubinaemia and UDP-glucuronosyltransferase 1A1
      (UGT1A1) polymorphism in adult HIV-infected Thai patients treated with indinavir.
AB  - OBJECTIVES: To investigate the association between the UGT1A1*6 (G71R) and
      UGT1A1*28 (promoter (TA)7-repeat) genotypes and hyperbilirubinaemia in Thai
      patients treated with indinavir, and characterize the inhibition of human UGTs by
      indinavir in vitro. METHODS: Ninety-six Thai HIV patients receiving indinavir,
      800 mg t.i.d. or 800 mg b.i.d. "boosted" with ritonavir (100 mg b.i.d.), had
      serum bilirubin levels measured to 24 weeks post-treatment and were genotyped for
      UGT1A1*6 and UGT1A1*28. The inhibition selectivity and kinetics of indinavir were
      determined using a panel of recombinant human UGTs. RESULTS: UGT1A1*6 and
      UGT1A1*28 frequencies in the Thai patients were 10.4% and 15.6%, respectively.
      Total, conjugated (direct) and unconjugated (indirect) serum bilirubin
      concentrations increased significantly at 24 weeks of indinavir treatment for all
      four genotypes, with a trend towards higher levels depending on the number of
      UGT1A1 mutant alleles; *6/*28 > *6 > *28 > reference. The hazards ratio (HR) for
      serious hyperbilirubinaemia (total bilirubin > 2.5 mg/dl) at week 24 was
      statistically significant only in those patients carrying the UGT1A1*6 (HR 2.87)
      and UGT1A1*6/*28 (HR 11.42) genotypes. The Ki values for indinavir inhibition of
      UGT1A1 and UGT1A1*6 were 4.1 and 10.7 mumol/l respectively. However, indinavir
      was also shown to inhibit other human UGTs, notably UGT1A3 and UGT1A7.
      CONCLUSIONS: In contrast to Caucasian HIV-infected patients treated with
      indinavir, the promoter polymorphism (UGT1A1*28) is of less significance than the
      coding region (UGT1A1*6) mutation as a risk factor for hyperbilirubinaemia. The
      Ki values determined for indinavir inhibition of UGT1A1 are consistent with an
      interaction in vivo, with an additive effect in patients with already impaired
      bilirubin glucuronidation activity.

PMID- 16609364
TI  - Restenosis after percutaneous coronary intervention is associated with the
      angiotensin-II type-1 receptor 1166A/C polymorphism but not with polymorphisms of
      angiotensin-converting enzyme, angiotensin-II receptor, angiotensinogen or heme
      oxygenase-1.
AB  - OBJECTIVES: The renin-angiotensin system (RAS) is thought to play a major role in
      the pathophysiology of de-novo restenotic lesions and in-stent restenosis after
      percutaneous coronary intervention (PCI). Heme oxygenase-1 (HO-1), is thought to
      beneficially influence these processes. We examined the effect of pharmacologic
      as well as genetic RAS interactions on restenosis in a large population of
      consecutive patients undergoing PCI, and evaluated possible gene-gene
      interactions in both systems. METHODS: The GENDER project is a multicenter
      prospective follow-up study, including 3146 patients after successful PCI.
      Genotyping in these patients was performed for the ACE gene insertion/deletion,
      the angiotensinogen 235Met/Thr, T174M and A(-6)G, the angiotensin-II type 1
      receptor (AT1R) 1166A/C and T810A, the angiotensin-II type 2 receptor (AT2R)
      1675G/A and 3123A polymorphisms and the length polymorphism in the HO-1 promoter
      region. RESULTS: A total of 3104 patients were followed for 10 months. In 2975
      patients at least one of the nine genotypes could be determined. The AT1R 1166 CC
      genotype showed a significant association with TVR; the other polymorphisms did
      not. RAS-inhibitory drugs were not associated with the incidence of TVR, nor did
      they interact with any of the investigated polymorphisms. Patients with the ACE
      I/I polymorphism showed a trend towards a better outcome if they had a short
      number of repeats in the HO-1 promoter. This relationship was inversely present
      in carriers of the ACE D/D polymorphism. CONCLUSION: We could only establish a
      role for the AT1R 1166A/C polymorphism in restenosis after PCI. However,
      significant gene-gene interaction was suggested for the ACE gene and the HO-1
      promotor. The RAS and HO-1 relation in restenosis merits further investigation.

PMID- 16609365
TI  - A -786T>C polymorphism in the endothelial nitric oxide synthase gene reduces
      serum nitrite/nitrate levels from the heart due to an intracoronary injection of
      acetylcholine.
AB  - We identified a -786T>C polymorphism in the eNOS gene, and this polymorphism was
      strongly associated with coronary spasm. The present study aimed to elucidate
      whether the -786T>C polymorphism or acetylcholine (ACh)-induced coronary spasm
      affects serum nitrite/nitrate (NOx) levels. The study population comprised three
      groups: (i) 26 patients without coronary spasm in the left anterior descending
      coronary artery (LAD) with the T/T genotype (group A); (ii) 20 patients with
      coronary spasm in the LAD with the T/T genotype (group B); and (iii) 16 patients
      with coronary spasm in the LAD with the C/T genotype (group C). Paired blood
      samples were obtained from the coronary sinus (CS) and the aortic tract (Ao)
      before and after an intracoronary injection of ACh. Serum NOx and plasma lactate
      levels were measured. The delta NOx level was calculated as the serum
      concentration of NOx in the CS minus that in the Ao. We compared lactate
      extraction ratios (LERs) and delta NOx levels between the three groups. The LERs
      after the provocation test in groups A, B and C were 18.9+/-2.4%, -0.5+/-3.9% and
      -13.5+/-4.2%, respectively. The LER in group C was significantly lower than in
      group B. The delta NOx levels after the provocation test in groups A, B and C
      were 11.5+/-1.7 micromol/l, 10.4+/-3.5 micromol/l and -2.1+/-4.8 micromol/l,
      respectively. The delta NOx levels in group C were significantly lower (P<0.05).
      Although the NOx level was significantly increased after the provocation test in
      group A (P<0.05), the NOx level was significantly decreased after the provocation
      test in group C (P=0.001). In group B, the provocation test did not significantly
      change the delta NOx level. In conclusion, the -786T>C polymorphism reduces the
      NOx level from the heart due to an intracoronary injection of ACh, and thereby
      predisposes the patients to severe coronary spasm.

PMID- 16609366
TI  - p53 polymorphic variants at codon 72 and the outcome of therapy in randomized
      breast cancer patients.
AB  - BACKGROUND: Adjuvant therapy of breast cancer patients reduces the risk of
      recurrence and mortality, although, a substantial proportion of patients acquire
      resistance and relapse in the disease. Predictors of therapeutic response are
      therefore important to avoid both therapy resistance and the side effects of
      inefficient regimes. The p53 protein is a key determinant to induce either growth
      arrest or apoptosis in response to cytotoxic stress. METHODS: In the search for
      predictive markers of cancer therapy we investigated a common Arg72/Pro72
      polymorphism in the p53 gene, which has been shown to influence the apoptotic
      potential. Using PCR and RFLP we genotyped 220 breast cancer patients randomized
      to radiotherapy versus chemotherapy and tamoxifen versus no tamoxifen. RESULTS:
      Oestrogen-receptor positive patients possessing at least one Pro72 allele had
      better distant recurrence-free survival when randomized to tamoxifen compared to
      those who were not (P=0.0033), as also demonstrated by the significantly
      decreased hazard ratio (HR=0.28, 95% CI 0.12-0.65). Among patients homozygous for
      the Arg72 genotype the outcome was approximately equal between tamoxifen treated
      and non-tamoxifen treated patients (P=0.65). When the calculated hazard ratios
      for the genotypes were compared by an interaction test a significant difference
      was found (P=0.0088). CONCLUSION: The present report indicates that the codon 72
      polymorphism in the p53 gene may be a predictor of tamoxifen response, suggesting
      that breast cancer patients lacking the Pro72 allele might be candidates for
      other therapies.

PMID- 16609367
TI  - A sensitive and rapid alternative to HLA typing as a genetic screening test for
      abacavir hypersensitivity syndrome.
AB  - BACKGROUND: Abacavir hypersensitivity reaction (ABC HSR) is a potentially life
      threatening adverse reaction that affects approximately 8% of patients that
      initiate this antiretroviral drug. Independent groups have shown a strong
      predictive association between ABC HSR and HLA-B*5701, indicating that exclusion
      of HLA-B*5701 positive individuals from abacavir treatment would largely prevent
      ABC HSR. However, the limited availability and relatively high cost of human
      leukocyte antigen (HLA) typing represent barriers to the widespread
      implementation of this pharmacogenetic approach to abacavir prescribing. To
      facilitate routine screening, we have developed a rapid flow cytometry method for
      HLA-B57 phenotyping using commercially available B17 monoclonal antibodies.
      METHODS: Whole blood samples from 84 human immunodeficiency virus (HIV) patients
      were examined by standard flow cytometry methods, using a two-colour B17-specific
      immunofluorescence assay in the CD45 lymphocyte population. RESULTS: All eight
      HLA-B57 individuals examined tested positive, while HLA-B57/58 negative
      individuals (n=74) tested negative for this flow cytometry test. Two non-HLA-B57
      individuals showed weak cross-reactivity. CONCLUSION: In our predominantly
      Caucasian population, B17/CD45 dual staining was sufficient to identify
      individuals carrying B17 cell surface antigens. This approach, utilizing flow
      cytometry methods that are widely available in HIV laboratories, therefore offers
      a sensitive, rapid and cost-effective screening assay prior to abacavir
      prescription. Following risk stratification with this assay, it would be
      anticipated that identification of HLA-B*5701 using molecular HLA typing methods
      would be required in <10% of the screened population.

PMID- 16609368
TI  - Search for an association between the human CYP1A2 genotype and CYP1A2 metabolic
      phenotype.
AB  - The genotype responsible for more than 60-fold interindividual differences in
      human hepatic CYP1A2 constitutive expression is not understood. Resequencing the
      human CYP1A1_CYP1A2 locus (39.6 kb) in five major geographically isolated
      subgroups recently led to the identification of 85 single nucleotide
      polymorphisms (SNPs), 57 of which were double-hit SNPs. Here, we attempted to
      correlate the CYP1A2 genotype with a metabolic phenotype. We chose 16 SNPs (all
      having a minor allele frequency > or =0.05 in Caucasians) to genotype 32 DNA
      samples (26 Caucasians, six Ethiopians) in which CYP1A2 metabolism had previously
      been determined. From 280 subjects (five locations worldwide) that had been
      CYP1A2-phenotyped, we genotyped the 10 highest, 14 lowest and eight intermediate
      DNA samples. Although no SNP was significant (P<0.05), possibly due to the small
      sample size, we found a trend for several of the six SNPs across the CYP1A2
      linkage disequilibrium block associated with the trait. Five CYP1A2 haplotypes
      were inferred, two of which had not previously been reported; haplotype 1A2H10
      showed the greatest association with CYP1A2 activity. Regulatory sequences
      responsible for the large interindividual differences in hepatic CYP1A2 gene
      basal expression might reside, in part, with some of these CYP1A2 SNPS but, in
      large part, might be located either cis (in nearby sequences not yet haplotyped)
      or trans in that they are not linked to the gene. We conclude that no SNP or
      haplotype in the CYP1A2 gene has yet been identified that can unequivocally be
      used to predict the metabolic phenotype in any individual patient.

PMID- 16609369
TI  - Lymphotoxin alpha gene in Crohn's disease patients: absence of implication in the
      response to infliximab in a large cohort study.
AB  - A haplotype in the lymphotoxin alpha (LTA) gene has been associated with a lack
      of response to infliximab in a small cohort of Crohn's disease (CD) patients. The
      present study aimed to confirm the implication of this haplotype in the response
      to infliximab in a larger cohort of Caucasian patients. The response to the first
      infusion with infliximab was evaluated in 214 Caucasian patients with either
      luminal (n=150) or fistulising (n=64) CD. Clinical response was based on the
      decrease in CD Activity Index (luminal) or on the evolution in the fistula
      discharge (fistulising). Biological response was assessed in 139 patients who had
      elevated C-reactive protein (CRP) before treatment and for whom CRP values were
      also available after treatment. A positive biological response was defined as a
      decrease in CRP of at least 25%. The patients were genotyped for six
      polymorphisms in the LTA gene. A positive clinical response was present in 65.4%
      of the patients and a positive biological response was observed in 80.6% of the
      patients. No association was found with any of the studied polymorphisms, nor
      with the previously published LTA haplotype and the response to infliximab. We
      could not confirm an association between the LTA locus and clinical or biological
      response to infliximab in a large cohort of CD patients.

PMID- 16609370
TI  - Remarkably low incidence of hypospadias in Greenland despite high exposure to
      endocrine disrupters; possible protective effect of androgen receptor genotype.
AB  - Endocrine disrupters, such as persistent organohalogen pollutants (POPs) may
      cause hypospadias, which is a common congenital anomaly in males, affecting 0.2
      0.7%. We hypothesized that hypospadias incidence would be high among
      Greenlanders, who are one of the most POP exposed populations on earth through
      consumption of contaminated sea mammals. Interestingly, among the 11 076 boys
      born in Greenland 1982-2002, only two cases of hypospadias were noted (incidence
      0.02%; 95% CI: 0.002-0.06). Normal male sexual differentiation is dependent on
      the androgen receptor (AR). AR function is regulated by polymorphic repeats of
      CAG and GGN trinucleotide bases. In Greenland 85% were carriers of GGN=23, which
      in a previous report was less frequent in patients with hypospadias than in the
      general population. This finding indicates that AR genotype could contribute to a
      genetic predisposition in Greenlanders, who despite one of the worlds highest
      body burden of POPs, seem to be protected from hypospadias.

PMID- 16609371
TI  - Functional characterization of a novel variant of estrogen receptor beta
      identified in screening of DNA derived from African Americans.
AB  - OBJECTIVE: Information on single nucleotide polymorphisms in the estrogen
      receptor beta (ERbeta) gene is lacking for the African American population.
      METHODS: In this study, we systematically screened the coding and flanking intron
      regions of the ERbeta gene in 49 healthy African American individuals. RESULTS:
      We detected four novel variants, of which one variant (963T-->C) resulted in
      amino acid change from phenylalanine to leucine at position 289, referred to as
      ERbetaF289L. This receptor variant was characterized in vitro for transcriptional
      activity and ligand-binding. These studies revealed that ERbetaF289L had reduced
      estrogen binding affinity and impaired response to 17beta-estradiol induced
      transactivation compared to the wild-type ERbeta. CONCLUSION: This novel variant
      might confer genetic susceptibility to certain endocrine related diseases in
      African Americans.

PMID- 16609372
TI  - Editorial.

PMID- 16609373
TI  - Osteotomy for distal radius malunion.

PMID- 16609374
TI  - A radiovolar approach to dorsal malunions of the distal radius.

PMID- 16609375
TI  - Pollicization of damaged fingers.

PMID- 16609376
TI  - Rolando's Fracture: Treatment by Closed Reduction and External Fixation.

PMID- 16609377
TI  - Bone lengthening in congenital hand conditions.

PMID- 16609378
TI  - Progressive bone distraction lengthening in the treatment of congenital
      malformations of the hand.

PMID- 16609379
TI  - Free flap coverage of palmar hand wounds.

PMID- 16609382
TI  - Editorial.

PMID- 16609380
TI  - Postoperative therapy after skin grafts and flaps to the hand.

PMID- 16609383
TI  - Surgical repair for scapholunate dissociation.

PMID- 16609384
TI  - Anatomic Reconstruction of the Distal Radioulnar Ligaments for DRUJ Instability.

PMID- 16609385
TI  - Combined Internal and External Fixation of Complex Intra-articular Distal Radius
      Fractures Using Dorsal and Volar Approaches.

PMID- 16609386
TI  - Metacarpophalangeal arthroscopy: technique and indications.

PMID- 16609387
TI  - Triceps transfer for deltoid dysfunction.

PMID- 16609388
TI  - Arthroscopic wafer for ulnar impaction syndrome.

PMID- 16609389
TI  - Use of mitek anchors in the digits.

PMID- 16609390
TI  - The medial surgical approach to the humerus.

PMID- 16609391
TI  - Arthroscopic treatment of partial and complete intercarpal ligament tears.

PMID- 16609393
TI  - Editorial.

PMID- 16609392
TI  - Postoperative management after total elbow replacement.

PMID- 16609394
TI  - Acutrak percutaneous scaphoid fixation.

PMID- 16609395
TI  - Percutaneous cannulated screw fixation of acute scaphoid fractures.

PMID- 16609396
TI  - Limited single-incision repair of distal tendon ruptures using suture anchors.

PMID- 16609397
TI  - Reattachment of the ruptured distal biceps tendon using a modified anterior
      approach.

PMID- 16609398
TI  - A new method for radiolunate arthrodesis in ulnar translocation of the carpus in
      the rheumatoid wrist.

PMID- 16609399
TI  - The double plating technique for distal radius fractures.

PMID- 16609400
TI  - Three-dimensional Dynamic External Fixation Combined with Bone Grafting for
      Kienbock's Disease.

PMID- 16609402
TI  - Diagnosis and treatment of ulnar nerve compression at the elbow.

PMID- 16609401
TI  - Sauve-kapandji procedure using the herbert cannulated bone screw.

PMID- 16609403
TI  - The surgical treatment of dupuytren contracture with the reverse flow dorsal
      metacarpal island flap.

PMID- 16609404
TI  - Postoperative Management of Dupuytren's Contracture.

PMID- 16609405
TI  - Editorial.

PMID- 16609406
TI  - Acute Dorsal Trans-scaphoid Perilunate Dislocations: Open Reduction and Internal
      Fixation.

PMID- 16609407
TI  - Surgical correction of extensor tendon subluxation and jlnar drift in the
      rheumatoid hand.

PMID- 16609408
TI  - Soft tissue procedures for the rheumatoid swan neck finger deformity.

PMID- 16609409
TI  - Distal biceps tendon repair: a single incision technique.

PMID- 16609410
TI  - Reconstruction of upper extremity function in brachial plexopathy using double
      free gracilis flaps.

PMID- 16609411
TI  - Dupuytren's Contracture: A Chart Review to Determine Benefits of Wound
      Irrigation.

PMID- 16609412
TI  - Functional Surgery of the Upper Limb in High-level Tetraplegia: Part I.

PMID- 16609413
TI  - Functional Surgery of the Upper Limb in High-level Tetraplegia: Part II.

PMID- 16609415
TI  - Useful surgical techniques to treat disorders of the hand and wrist.

PMID- 16609414
TI  - General principles of rehabilitation after surgical reconstruction of the
      rheumatoid hand.

PMID- 16609416
TI  - Scapholunate dissociation: treatment with the dorsal intercarpal ligament
      capsulodesis.

PMID- 16609417
TI  - Stabilization of the unstable distal ulna: the Linscheid-Hui procedure.

PMID- 16609418
TI  - A simple technique for decompression of the posterior interosseous nerve.

PMID- 16609419
TI  - Symbrachydactyly: a clinical entity.

PMID- 16609420
TI  - Operative exposure of fractures of the distal radius.

PMID- 16609421
TI  - The hypothenar fat flap for revision carpal tunnel surgery.

PMID- 16609422
TI  - Staple use in intraoperative skin retraction: a technique report.

PMID- 16609423
TI  - Staged reconstruction of zone II flexor tendon injuries in the child.

PMID- 16609424
TI  - Thumb polydactyly.

PMID- 16609427
TI  - Certificate of added qualifications in hand surgery: history, status, and future.

PMID- 16609425
TI  - Rehabilitation for secondary flexor tendon reconstruction in children.

PMID- 16609428
TI  - Bone revascularization by vessel implantation for the treatment of Kienbock
      disease.

PMID- 16609429
TI  - Use of skeletal traction for early Kienbock's disease.

PMID- 16609430
TI  - Distal scaphoid excision in scaphoid-trapezium-trapezoid arthritis.

PMID- 16609431
TI  - Traction reduction and cast immobilization for the treatment of boxer's
      fractures.

PMID- 16609432
TI  - The Stein and Gill technique for wrist arthrodesis.

PMID- 16609433
TI  - Contralateral C7 transfer (CC-7T) for avulsion injury of the brachial plexus.

PMID- 16609434
TI  - Ununited fractures of the clavicle with bony defect: treatment with
      corticocancellous interposition bone graft and plate fixation.

PMID- 16609435
TI  - Skin flap in first web retraction.

PMID- 16609436
TI  - Intraoperative use of an external fixator distraction device for corrective
      distal radius osteotomy.

PMID- 16609437
TI  - Rehabilitation aspects of external fixation for distal radius fractures.

PMID- 16609439
TI  - Open wound technique for high-pressure injection injuries of the hand.

PMID- 16609440
TI  - Technique for distal replantation.

PMID- 16609441
TI  - Surgical approach to the radial nerve.

PMID- 16609442
TI  - Anatomic anomalies and carpal tunnel syndrome: a review.

PMID- 16609443
TI  - Vascularized bone grafting for scaphoid nonunion.

PMID- 16609444
TI  - Third and fourth finger ray amputations by intracarpal osteotomy.

PMID- 16609445
TI  - Arthrodesis of digital joints for congenital hand condition.

PMID- 16609446
TI  - Interposition vein graft configurations for microsurgical revascularization of
      the ischemic hand.

PMID- 16609447
TI  - Opponensplasty.

PMID- 16609448
TI  - Rehabilitation techniques for applying immediate active tension to the repaired
      extensor system.

PMID- 16609449
TI  - Treatment for congenital differences of the hand and upper extremity.

PMID- 16609450
TI  - Radialization for radial club hand.

PMID- 16609451
TI  - DRUJ contracture release.

PMID- 16609452
TI  - Free muscle transfer in brachial plexus palsy.

PMID- 16609453
TI  - Proximal row carpectomy.

PMID- 16609454
TI  - Functional reconstruction of the metacarpal hand with multiple toe
      transplantations.

PMID- 16609455
TI  - Arthroscopic repair of radial-sided triangular fibrocartilage complex lesions.

PMID- 16609456
TI  - Percutaneous trigger finger release.

PMID- 16609457
TI  - Distraction arthrolysis for PIP joint contracture using an external fixator.

PMID- 16609458
TI  - Postoperative management of the dorsal fracture-dislocation of the proximal
      interphalangeal joint.

PMID- 16609460
TI  - Dorsal stabilization of the distal radioulnar joint.

PMID- 16609461
TI  - New technique for ulnar shortening osteotomy.

PMID- 16609462
TI  - Treatment of comminuted distal radius with the use of an internal distraction
      plate.

PMID- 16609463
TI  - Single incision repair of distal biceps tendon rupture.

PMID- 16609464
TI  - Improving the result of vascularized joint transfer in hand joints: two-stage
      reconstruction with two periods of rehabilitation.

PMID- 16609465
TI  - Primary repair of the scapholunate ligament.

PMID- 16609467
TI  - New trends in hand burn.

PMID- 16609466
TI  - Adjuvant hyperbaric oxygenation therapy in hand edema and ischemia.

PMID- 16609468
TI  - Rehabilitation of the burned hand.

PMID- 16609471
TI  - Factitious disorders.

PMID- 16609472
TI  - Vascularized pedicled bone grafts for disorders of the carpus.

PMID- 16609473
TI  - Abduction-opposition wedge osteotomy of the base of the first metacarpal for
      thumb basal joint arthritis.

PMID- 16609475
TI  - Scaphoid osteotomy for malunion.

PMID- 16609474
TI  - Arthroplasty of MP and PIP joints using a chondroperichondrial graft.

PMID- 16609476
TI  - Vascularized joint transfer for radial club hand.

PMID- 16609477
TI  - Rehabilitation programs for the surgical management of obstetrical brachial
      plexus injuries in the early and late phases.

PMID- 16609479
TI  - Treatment options for lunotriquetral dissociation.

PMID- 16609480
TI  - Direct ligamentous repair of scapholunate dissociation with capsulodesis
      augmentation.

PMID- 16609481
TI  - Partial denervation of the wrist: a new approach.

PMID- 16609482
TI  - Treatment of Bennett's and Rolando's fractures.

PMID- 16609483
TI  - Free composite graft to claw nail deformity using the ice water cooling method.

PMID- 16609484
TI  - Zone I-V extensor tendon repair.

PMID- 16609485
TI  - Peripheral nerve monitoring during surgery for upper extremity lengthening.

PMID- 16609486
TI  - Limited open incision carpal tunnel release.

PMID- 16609487
TI  - Bone lengthening with the Ilizarov apparatus for congenital club hands.

PMID- 16609488
TI  - Rehabilitation of radial club hand.

PMID- 16609489
TI  - New and innovative techniques in hand and upper extremity surgery.

PMID- 16609490
TI  - Arthroscopic treatment of triangular fibrocartilage complex tears.

PMID- 16609491
TI  - Midcarpal arthrodesis: four-bone technique.

PMID- 16609492
TI  - Prognostic factors for return to work following musculoskeletal symptoms of
      unknown etiology.

PMID- 16609493
TI  - Proximal row carpectomy and soft tissue interposition arthroplasty.

PMID- 16609494
TI  - Digital prostheses and orthotics: matching form with function.

PMID- 16609495
TI  - The RASL procedure: reduction and association of the scaphoid and lunate using
      the Herbert screw.

PMID- 16609496
TI  - How meaningful is the literature?

PMID- 16609497
TI  - Flexor tendon repairs.

PMID- 16609498
TI  - Rehabilitation techniques for applying immediate active tension to zone I and II
      flexor tendon repairs.

PMID- 16609501
TI  - Bone-grafting techniques for scaphoid nonunion.

PMID- 16609500
TI  - Clinical entities that can be approached and treated in several different ways.

PMID- 16609502
TI  - Wave plate osteosynthesis in the upper extremity.

PMID- 16609503
TI  - Arthroscopic treatment of TFCC tears.

PMID- 16609504
TI  - Mobilization of congenital proximal radio-ulnar synostosis: a technical detail.

PMID- 16609505
TI  - Lateral band rerouting in the treatment of swan neck deformities due to cerebral
      palsy.

PMID- 16609506
TI  - Evaluation and treatment of the painful neuroma.

PMID- 16609507
TI  - Prognostic factors for return to work following severe hand injuries.

PMID- 16609508
TI  - Rehabilitation following surgery for the distal radioulnar joint.

PMID- 16609509
TI  - Fractures of the distal radius: significant improvement in the treatment.

PMID- 16609510
TI  - A minimally invasive distal radial osteotomy for treatment of distal radius
      fracture malunion.

PMID- 16609511
TI  - Use of the Forte plate in unstable, dorsally displaced fractures of the distal
      radius.

PMID- 16609512
TI  - Intramedullary bone- cement fixation for colles fracture in elderly patients.

PMID- 16609513
TI  - Extension block with Kirschner wire for fracture dislocation of the distal
      interphalangeal joint.

PMID- 16609514
TI  - Surgical techniques for revascularization in the chronically ischemic hand.

PMID- 16609515
TI  - Arthroscopic proximal row carpectomy.

PMID- 16609516
TI  - The tube concept in nerve repair.

PMID- 16609517
TI  - Operative fixation of fractures of the distal radius using the pi plate.

PMID- 16609519
TI  - Upper extremity ulnar compressive neuropathy: surgical technique and return to
      work status.

PMID- 16609518
TI  - A safe method of Bunnell criss-cross suture.

PMID- 16609520
TI  - Postoperative management for ulnar nerve neuropathy.

PMID- 16609522
TI  - A fiber-splitting capsulotomy technique for dorsal exposure of the wrist.

PMID- 16609524
TI  - Limited-incision carpal tunnel release.

PMID- 16609523
TI  - Occupational conditions: how I perform an independent medical evaluation.

PMID- 16609525
TI  - A new computer-based documentation system for hand injury.

PMID- 16609526
TI  - Applications of botulinum toxin in orthopedics and upper extremity surgery.

PMID- 16609527
TI  - Vein wrapping for the treatment of recurrent carpal tunnel syndrome.

PMID- 16609529
TI  - Intrinsic flaps in the hand: new concepts in skin coverage.

PMID- 16609528
TI  - Intramedullary Herbert screws for treatment of phalangeal nonunion.

PMID- 16609530
TI  - Postoperative management of skin grafts, flaps, and tissue transfers of the hand.

PMID- 16609538
TI  - [79th annual SO.F.C.O.T. meeting.]

PMID- 16609539
TI  - [Minutes of the General Assembly.]

PMID- 16609540
TI  - [Total elbow prostheses.]

PMID- 16609541
TI  - [Forearm shaft fractures.]

PMID- 16609542
TI  - [Technological innovations: new perspectives for "multidisciplinary" orthopedic
      surgery.]

PMID- 16609543
TI  - [Prospective and retrospective study of complications after centromedullary
      nailing of weight-bearing bones (CECOP study).]

PMID- 16609544
TI  - [Gait and movement analysis: necessity or luxury.]

PMID- 16609546
TI  - [Editorial].

PMID- 16609545
TI  - [Minimally invasive surgery (MIS).]

PMID- 16609547
TI  - [Outpatient surgery: regulations and current situation].

PMID- 16609548
TI  - [The long head of the biceps].

PMID- 16609549
TI  - [Anterior cruciate ligament and rotation stability].

PMID- 16609551
TI  - [Minimally invasive total knee arthroplasty].

PMID- 16609550
TI  - [Minimally invasive hip surgery: update and review of the literature].

PMID- 16609552
TI  - [Arthroscopic repair of full-thickness cuff tears: a multicentric retrospective
      study of 576 cases with anatomical assessment].
AB  - PURPOSE OF THE STUDY: Totally arthroscopic repair of rotator cuff tears is now
      common practice. The techniques used were evaluated by a retrospective
      multicentric analysis conducted by the French Society of Arthroscopy. MATERIAL
      AND METHODS: The series was limited to arthroscopic repair of full thickness
      tears of the supraspinatus or infraspinatus evaluated using the Constant score
      and arthro-MRI or arthroscan performed with at least one year follow-up. Data
      were processed with SPSS 10. The series included 576 patients who underwent
      surgery between January 2001 and June 2003. Mean patient age was 57.7 years; 52%
      were men and 60% were manual laborers. The mean preoperative Constant score was
      46.4 +/- 13.4/100. The tear was limited to the supraspinatus in 69% of shoulders,
      with extension to the upper third of the infraspinatus in 23.5% and the entire
      infraspinatus in 7.5%. The supraspinatus tear was distal in 41.7% of shoulders,
      intermediary in 44% and retracted in 14.3%. Fatty degeneration of the
      supraspinatus was noted grade 0 in 60%, 1 in 27%, 2 in 11% and 3 in 2%.
      Arthroscopic repair was performed in all cases, with locoregional anesthesia in
      60.9%. Bioresorbable implants were used in 33% and metallic implants in 62.1%.
      Acromioplasty was performed in 92.7% and capsulotomy in 14.9%. RESULTS: On
      average, the subjective outcome was scored 8.89/10. The Constant score improved
      from 46.3 +/- 13.4 to 82.7 +/- 10.3 with 62% having a strictly pain free
      shoulder. Muscle force improved from 5.8 +/- 3.7 to 13.6 +/- 5.4. Outcome was
      excellent in 94% of shoulders at 18.5 months mean follow-up. The complication
      rate in this series was 6.2% with 3.1% prolonged stiffness, 2.7% reflex
      dystrophy, 0.2% infection, and 0.2% anchor migration. The cuff was considered
      normal in 55.7% of shoulders with an intratendon addition image in 19%, i.e.
      74.7% of non-ruptured cuffs. Minimal loss of integrity was noted in 9.5% and was
      marked in 15.7%, i.e. 25.2% iterative tears.ANATOMOCLINICAL CORRELATIONS: The
      Constant score was strongly correlated with rotator cuff integrity (p<0001). This
      correlation was also found for force (p<0001), motion (0.01) and activity (0.04),
      but not for pain. The clinical outcome was correlated with extension, retraction,
      intrasubstance tear, and fatty degeneration of the lesion preoperatively.
      Anatomic results were statistically less favorable for tears which were older,
      extensive, retracted or associated with fatty degeneration. Age was correlated
      with extent of the initial tear and also with less favorable anatomic and
      clinical outcome. Occupational accidents were correlated with less favorable
      clinical outcome. CONCLUSION: Functional improvement after healing is a strong
      argument for repair. Arthroscopy has the advantage of combining a low
      complication rate with good clinical and anatomic results. Age is correlated with
      functional outcome and healing, but is not a contraindication.

PMID- 16609553
TI  - ["Isolated" injury of the posterior cruciate ligament. Surgical treatment of
      isolated posterior cruciate ligament tears: a multicentric retrospective study of
      103 patients].
AB  - PURPOSE OF THE STUDY: We present a retrospective multicentric series of carefully
      selected patients presenting "isolated" laxity of the posterior cruciate
      ligament. MATERIAL AND METHODS: The series included 103 patients who were
      reviewed clinically (with a dedicated review chart) and radiographically with
      measurement of posterior laxity (Telos 15 kg). RESULTS: In these patients with an
      isolated injury of the PCL (without associated injury of the peripheral ligament)
      DISCUSSION: The short follow-up of this series (four years) does not enable an
      assessment of the risk or benefit of PCL ligamentoplasty for arthrosic knees.

PMID- 16609554
TI  - [Not Available].

PMID- 16609555
TI  - [Not Available].

PMID- 16609557
TI  - [Not Available].

PMID- 16609556
TI  - [Not Available].

PMID- 16609558
TI  - [Not Available].

PMID- 16609559
TI  - [Not Available].

PMID- 16609560
TI  - [Not Available].

PMID- 16609561
TI  - [Not Available].

PMID- 16609562
TI  - [Not Available].

PMID- 16609563
TI  - [Not Available].

PMID- 16609564
TI  - [Not Available].

PMID- 16609565
TI  - [Not Available].

PMID- 16609566
TI  - [Not Available].

PMID- 16609567
TI  - [Not Available].

PMID- 16609568
TI  - [Not Available].

PMID- 16609569
TI  - [Not Available].

PMID- 16609570
TI  - [Not Available].

PMID- 16609571
TI  - [Not Available].

PMID- 16609572
TI  - [Not Available].

PMID- 16609573
TI  - [Not Available].

PMID- 16609574
TI  - [Not Available].

PMID- 16609575
TI  - [Not Available].

PMID- 16609576
TI  - [Not Available].

PMID- 16609577
TI  - [Not Available].

PMID- 16609578
TI  - [Not Available].

PMID- 16609579
TI  - [Not Available].

PMID- 16609580
TI  - [Not Available].

PMID- 16609581
TI  - [Not Available].

PMID- 16609582
TI  - Resultats a deux ans du traitement chirurgical de 35 laxites posterieures
      chroniques du genou.

PMID- 16609583
TI  - [Not Available].

PMID- 16609584
TI  - [Not Available].

PMID- 16609585
TI  - [Not Available].

PMID- 16609586
TI  - [Not Available].

PMID- 16609587
TI  - [Not Available].

PMID- 16609588
TI  - Arthroscopic repair of large cuff tears using patching and augmentation of
      remaining defects with Restore: presentation and description of a new
      arthroscopical method.

PMID- 16609589
TI  - [Not Available].

PMID- 16609590
TI  - [Not Available].

PMID- 16609591
TI  - [Not Available].

PMID- 16609592
TI  - [Not Available].

PMID- 16609593
TI  - [Not Available].

PMID- 16609594
TI  - [Not Available].

PMID- 16609595
TI  - [Not Available].

PMID- 16609596
TI  - [Not Available].

PMID- 16609597
TI  - A biomechanical comparison of the Mitek RapidLoc, Mitek meniscal repair system,
      clearfix screws and vertical PDS and Ti-Cron sutures.

PMID- 16609598
TI  - [Not Available].

PMID- 16609599
TI  - Reconstruction a double faisceaux du LCA avec un transplant d'ischio
      jambiers/Resultats a 18 mois d'une etude prospective.

PMID- 16609600
TI  - [Not Available].

PMID- 16609601
TI  - [Not Available].

PMID- 16609602
TI  - [Not Available].

PMID- 16609604
TI  - [Not Available].

PMID- 16609603
TI  - [Not Available].

PMID- 16609605
TI  - [Not Available].

PMID- 16609606
TI  - [Not Available].

PMID- 16609607
TI  - [Not Available].

PMID- 16609608
TI  - [Not Available].

PMID- 16609609
TI  - [Not Available].

PMID- 16609610
TI  - [Not Available].

PMID- 16609611
TI  - [Not Available].

PMID- 16609612
TI  - [Quality of information transfer for informed consent: an experimental study in
      21 patients].
AB  - PURPOSE OF THE STUDY: Delivering information to the patient, an ethical
      obligation recognized for years, has recently become a legal obligation. Proof of
      information delivery has become the legal responsibility of the surgeon. We
      conducted a prospective study to evaluate the quality of information transfer by
      assessing patient comprehension of information delivered in an orthopedic surgery
      unit. MATERIAL AND METHODS: All patients attending consultations before
      undergoing arthroscopic treatment for rotator cuff tendinopathy were enrolled in
      this study when the consultation was conducted in the presence of an observer.
      Two questionnaires, one for the patient and one for the surgeon, were used to
      collect given information about the pathological condition, the modalities of
      treatment, and the expected results of the treatment and its complications.
      RESULTS: All 21 patients included in the study considered they had been well
      informed and that they had understood their pathological condition as well as the
      complications of the proposed treatment. However, agreement between their stated
      comprehension and the information delivered was poor, varying from 15 to 50%.
      Furthermore, 90% of the patients stated they had understood the potential
      complications of the surgical procedure, despite the fact that the consulting
      surgeons had not (generally) provided information on such complications.
      DISCUSSION: There is a gap between what the surgeon says (or thinks he/she says)
      and what the patient understands. Potential biases in this study (non-unbiased
      observer) might explain this discordance which was probably related to the
      unequal relationship between the patient and the physician for any consultation.
      Therefore, the basis of informed consent cannot be found in the details
      concerning complications actually delivered to the patient. Surgeons must become
      aware that the patients understand very little of their explanations. This does
      not mean that the information should not be delivered but on the contrary that it
      must be. The important point is not necessarily the information content but
      rather the quality of the human relationship enabling information transfer.

PMID- 16609613
TI  - [Retrograde locked nailing of humeral shaft fractures: a prospective study of 58
      cases].
AB  - PURPOSE OF THE STUDY: Appropriate treatment for humeral shaft fractures remains a
      debated issue. Among the classical osteosynthesis techniques proposed, closed
      nailing was adapted to the humerus rather late, using the anterograde method. Use
      of retrograde nailing, which spares the rotator cuff, is more recent. The purpose
      of this study was to report outcome in 58 humeral shaft fractures in adults
      treated using the universal humeral nail between January 2000 and December 2003.
      MATERIAL AND METHODS: This work was limited to recent shaft fractures in adults
      with non-pathological bones. The fractures included were all situated between the
      insertion of the pectoralis major and a point situated 2 cm above the apex of the
      olecraneum fossa. The series included 58 patients with 58 humeral shaft
      fractures. All fractures were closed except four (Gustilo type I and II). Two
      patients presented preoperative radial paralysis which was not considered to be a
      contraindication for retrograde locking nailing. The paralysis recovered in both
      patients, after neurolysis performed during the nailing procedure in one.
      Osteosynthesis was performed without opening the fracture focus under
      fluoroscopic control using a static locking nail inserted retrograde in patients
      in the supine position. RESULTS: There were two early deaths unrelated to the
      method. Healing was obtained in the surviving patients within fifteen weeks on
      average. Bone healing was primary in 53 patients and after secondary compression
      in three. At last follow-up, shoulder motion was normal in 88% of patients and
      elbow motion in 91%. The Rommens functional score was good in 84%. Complications
      included three cases of spontaneously regressive postoperative radial paralysis,
      three cases of reflex dystrophy including two which regressed, and two cases of
      humeral palette fracture requiring surgical osteosynthesis. The proximal screws
      were removed in six patients because of pain or migration. To date, implants have
      been removed in three patients without problem. There were no infections.
      CONCLUSION: Retrograde insertion of this nail facilitates treatment of humeral
      shaft fractures by allowing immediate joint motion and the advantages of closed
      reduction: no infection, no late bone healing requiring conversion to another
      method of fixation. The residual technical problems concern proximal nailing and
      nail introduction.

PMID- 16609614
TI  - [Life experience of adults with unilateral agenesia of the forearm: effect of
      prosthesis on self image and social relations].
AB  - PURPOSE OF THE STUDY: This study was devoted to better understanding how adults
      with agenesia of the forearm live their condition. The malformation studied was
      identical to that of a previous study in children. The present study was designed
      to provide professionals and parents with a reference system for making
      therapeutic decisions. MATERIAL AND METHODS: An intensive survey using semi
      directive interviews was conducted among adults aged 19 to 37 years, 12 women and
      8 men, with unilateral agenesia of the forearm. The majority of the participants
      had an occupation and an active social and familial life. RESULTS: The survey
      revealed factors of limitation or progress, expectations and renouncements,
      marking the life experience of these persons. The prosthesis had a significant
      impact on their lives. DISCUSSION: Four types of life experience could be
      identified from the survey data. All four could be understood as a search for
      equilibrium between internal reality (desired self image) and external reality
      (image produced by the physical and human environment via the regards of others
      and obstacles encountered). Several modalities for using a prosthesis, several
      ways of coping with the absence of a hand, with or without a prosthesis, and
      several ways of constructing a self-representation were distinguished. Rather
      than a functional disability, agenesia was found to be perceived as a persistent
      problem in daily life, generating handicap- or discrimination-producing
      situations. CONCLUSION: Forearm agenesia creates a situation different from
      normal and as such makes the question of self-identity and social relations more
      complex than for others. The comments provided by these young adults who cope
      with the paradoxical condition of an amputated but functional body demonstrated
      the central role of the body.

PMID- 16609615
TI  - [Electromyographic study of stretch reflexes in the normal and prosthetic hip].
AB  - PURPOSE OF THE STUDY: Several studies have been devoted to the effect of
      proprioception on joint function. Modifications in feedback control from the cord
      have been observed in unstable joints due to capsule and ligament laxity. A few
      studies have examined the effect of knee and hip arthroplasty on proprioception,
      but none have established whether stretch reflexes affect function of a
      prosthetic joint. The purpose of the present study was to demonstrate the
      electromyographic characteristics of stretch reflexes of the normal hip joint and
      to compare them with those observed in the prosthetic hip. MATERIAL AND METHODS:
      Two groups of patients were studied. The first included eleven subjects free of
      neurological disorders whose studied limb was healthy. The second group included
      ten subjects with a total hip prosthesis who had undergone extensive capsulectomy
      during the arthroplasty. Voluntary muscle contraction was noted in each subject.
      In addition, electromyographic recordings were made to note response of the
      ipsilateral and contralateral quadriceps crural and tensor of the fascia lata
      during changes in joint position. Recordings were made with the subject in the
      supine position, the limb suspended, hip flexed at 45 degrees and knee extended.
      Three series of ten recordings were made in random order to measure the latency
      of muscle response to free fall of the limb, accelerated fall of the relaxed
      limb, and accelerated fall associated with calibrated contraction of the
      quadriceps. Mean latency of muscle response was calculated for each trial.
      RESULTS: In the conditions of this study, there was no statistically significant
      difference (p = 0.05) in the reflex time course between natural and prosthetic
      hips. DISCUSSION: Changes due to joint replacement and capsulectomy do not appear
      to affect the stretch reflexes of the hip joint.

PMID- 16609616
TI  - [The cemented Muller straight stem total hip prosthesis with polyethylene cup and
      28 mm head: ten-year results].
AB  - PURPOSE OF THE STUDY: The purpose of this study was to evaluate the 10-year
      results of the cemented Muller straight stem total hip prosthesis with
      polyethylene cup and 28 mm head. MATERIAL AND METHOD: From May 1988 to May 1990,
      187 cemented prostheses (second-generation technique) were implanted via a
      transgluteal approach for degenerative hip disease. A Protasul 10 straight stem
      with a 28 mm modular head and a gamma ray sterilized polyethylene cup was used in
      all cases. At ten years, the follow-up of the 187 implants was: 60 implants in
      deceased patients, 24 implants in patients contacted by telephone (all with
      implants in place), 90 implants in 82 patients seen for review. The series thus
      included 40 women and 42 men, mean age 65 years. The clinical outcome was
      assessed with the Postel Merle d'Aubigne (PMA) score. Radiographic assessment
      noted lucent lines, granulomas, implant migration, polyethylene wear, and
      ossifications. Survival curves were established with the actuarial method.
      RESULTS: Among the 187 implants, two patients required revision: one for sepsis
      and the other for posttraumatic dislocation. Among the 82 patients reviewed at 10
      year, the PMA score was 16.8 (92% good and very good results). Radiographically,
      assessment of the acetabular component demonstrated three probable and one
      certain loosening, four cases of polyethylene wear greater than 2 mm. At the
      femoral level, osteolysis was noted in zones 1, 3, and 7 and rarified bone in
      zone 7 in four patients. Linear penetration of the stem into the cup was 0.09
      mm/yr, corresponding to a volumetric wear of 55, 35 mm3/year. Brooker grade 3
      ossification was observed in 27% of men and 14% of women. DISCUSSION: The
      clinical results were comparable to other series of cemented prostheses. At ten
      years, acetabular loosening was more frequent with active radiolucent lines
      present from the fifth year. It would thus appear that better results could be
      achieved by optimizing the bearing. Furthermore, there was no parallelism between
      the clinical and anatomic observations, cup loosening and femoral osteolysis were
      well tolerated. The prevention of ossification appears to be an important point,
      particularly in men.

PMID- 16609617
TI  - [Screw fixation without bone graft of calcaneal joint fractures: 35 cases].
AB  - PURPOSE OF THE STUDY: The prognosis of calcaneal joint fractures is less
      favorable than fractures without joint involvement. Surgical treatment is
      frequently recommended. The type of fixation and the usefulness of a bone graft
      remain subjects of debate. The purpose of this work was to present the functional
      and anatomic results obtained with simple screw fixation without bone grafting in
      a retrospective series of 35 displaced joint fractures of the calcaneus. MATERIAL
      AND METHODS: The series included 31 patients (four bilateral fractures), 86% men.
      Mean age was 36 years (17-60 years). Using the Duparc classification, there were
      12% type III fractures and 88% type IV fractures. Horizontal joint impaction was
      observed in 36% of patients, vertical impaction in 8%, and mixted impaction in
      56%. The mean Bohler angle was 2 degrees (range -25 degrees to 15 degrees ).
      According to the Utheza classification, 70% of the fractures had two sagittal
      fracture lines, 16.5% one sagittal fracture line, and 13.5% comminutive
      fractures. Incongruency of the subtalar joint was noted in 70%, with a conflict
      with the lateral malleolus in 50%. Mean time to surgery was 12 days (7-30 days).
      The sub- and retromalleolar approach was used to achieve simple screw fixation.
      Bone grafts were not used. Mean follow-up was two years (range 12-38 months).
      RESULTS: There were no serious complications. Functional outcome was analyzed
      with the Kitaoka scale, mean score 74.3 +/- 1.1 (range 46-98), with 16% excellent
      outcome, 56% good outcome, 25.2% fair outcome, and 2.5% poor outcome. There was a
      correlation between functional outcome and age, etiology, and type of fracture.
      Anatomic results were assessed with the Babin scale and were very good in 24%,
      good in 8%, fair in 28%, and poor in 40%. Secondary loss of the initial
      heightening of the joint surface was noted in 48% of the cases, 3 degrees on
      average. DISCUSSION: This series confirms the value of surgical treatment
      compared with conservative treatment. Compared with plate fixation, screw
      fixation exposes the patient to less risk of skin and infectious problems. Simple
      screwing generally provides satisfactory results with acceptable stability. In
      light of the present results, adjunction of a bone graft would not be necessary
      since the loss of correction of the joint surface height was often minimal.
      CONCLUSION: Screw fixation of calcaneal joint fractures is a reliable technique.
      Adjunction of a bone graft does not appear to be necessary.

PMID- 16609618
TI  - [Optoelectronic gait analysis after metatarsophalangeal arthrodesis of the
      hallux: fifteen cases].
AB  - PURPOSE OF THE STUDY: Degeneration of the metatarsophalangeal joint of the hallux
      is a frequent secondary lesion of the first ray subsequent to hallux valgus.
      Different surgical techniques have been proposed for cure, including
      metatarsophalangeal arthrodesis. Joint fusion relieves pain but sacrifices joint
      motion. The purpose of this work was to assess changes observed in gait after
      metatarsophalangeal arthrodesis of the hallux using a three-dimensional
      optoelectronic system. MATERIAL AND METHODS: Gait analysis was performed with a
      Vicon 3D system with five cameras and two AMTI force platforms in twelve patients
      who had undergone metatarsophalangeal arthrodesis more than six months earlier.
      The kinetic and kinematic curves and ground reaction forces were analyzed.
      Changes in the gait cycle and any compensations observed in the talocrural and
      interphalangeal joints were noted in the three dimensions. Wilcoxon test for
      paired series was applied for the statistical analysis. RESULTS: The general gait
      parameters and kinetic and kinematic values were not modified (excepting a non
      significant decline in maximal dorsiflexion of the ankle joint). There was a
      significant decrease in propulsion force in the anteroposterior and vertical
      planes, with significantly later heal lift-off and systematic displacement of
      ground reaction forces anterior to the metatarsophalangeal joint on the
      arthrodesis side. Reflectors positioned on the distal extremity of the hallux
      demonstrated that the essential part of compensation occurred at the level of the
      interphalangeal joint. DISCUSSION: Gait analysis after tibiotalar arthrodesis has
      been widely reported in the literature. The consequence of joint fusion on the
      rear foot and/or the torsion couple have also been studied. However, to our
      knowledge, there has been only one report using a different methodology devoted
      to metatarsophalaneal arthrodesis of the hallux. In this study, only step length
      and interphalangeal moment as well as ankle force were found to be decreased.
      Function of the interphalangeal joint was not assessed. The Vicon system enabled
      an adapted study of gait after metatarsophalangeal arthrodesis. This method
      offers several perspectives: study of the effect of the position of the
      arthrodesis in the sagittal plane on gait, changes over time in interphalangeal
      joint motion, or consequences of fusion on walking up and down stairs.
      CONCLUSION: Metatarsophalangeal arthrodesis of the hallux does not modify general
      gait parameters nor the kinetic and kinematic values. Compensation is achieved
      via the interphalangeal joint.

PMID- 16609619
TI  - [Septic dislocation of the hip secondary to BCG vaccination].
AB  - We report a case of septic dislocation of the hip in an eight-month-old infant
      secondary to BCG vaccination. The usual treatment of septic arthritis with
      surgical drainage and broad spectrum antibiotics was unsuccessful. Cure was
      achieved after institution of an anti-tuberculosis treatment and a second
      surgical drainage. This rare complication of BCG vaccination can develop several
      months after administration of the vaccine. Diagnosis is often difficult to
      establish due to the minimal clinical and non-specific clinical expression. Early
      radiological signs are also non-specific. Identification of the causal agent can
      be most difficult. Certain diagnosis is generally achieved after biopsy and
      pathology examination. Despite the attenuated virulence of the vaccine, anti
      tuberculosis treatment is indispensable to achieve cure. Surgery drainage alone
      is insufficient.

PMID- 16609620
TI  - [Acute limb ischemia and fracture of the pelvic ring: a case report].
AB  - We report the case of traffic accident victim who suffered multiple injuries
      after being ejected from the vehicle. The patient suffered blunt trauma of the
      pelvis followed by acute ischemia of the lower limb. The initial work-up revealed
      minimally displaced fractures of the right and left obturator rings and the left
      sacral wing, as well as a non-displaced fracture of the anterior wall of the
      acetabulum. Computed tomography eliminated a compressive retroperitoneal
      hematoma. The mechanism of the injury was direct blunt trauma rupturing an
      atheroma plaque which led to thrombosis of the left common femoral artery.
      Thrombectomy three hours 30 minutes after onset of ischemia enabled complete
      sensorial and motor recovery. Awareness of this unusual type of injury can be
      helpful in conducting a rigorous physical examination to ensure rapid diagnosis
      and treatment.

PMID- 16609621
TI  - [Low-grade central chondrosarcoma: difficult diagnosis in an adolescent girl].
AB  - Central chondrosarcoma of the tibia is exceptional, particularly in young
      patients. Low-grade tumors raise difficult problems for histological distinction
      with enchondroma. We report a case of grade 1 chondrosarcoma located in the upper
      portion of the tibia in a 17-year-old girl. After radical surgery, outcome was
      favorable with no recurrence or metastasis at three years follow-up. The
      distinction between low-grade central chondrosarcoma and enchondroma is one of
      the most difficult challenges in bone pathology. Clinical, radiographic and
      pathological data must be considered together to reach certain diagnosis.

PMID- 16609622
TI  - [Orthopedic treatment of spinal deformities in infancy and early childhood].
AB  - Surgical treatment of spinal deformities in infancy and early childhood (before
      age 6) is often very useful if the lesion is localized and curable by one unique
      surgery, such as hemivertebra resection and fusion. On the contrary, if the
      lesion, whether idiopathic or paralytic, is extended to a large part of the
      spine, early surgical treatment in infancy gives very disappointing results and
      often worsens the status of the child, especially respiratory function if the
      lesion is mainly thoracic. The goal of this paper is to explain in detail
      indications and management of non-surgical treatment of such lesions. These are
      variable according to localization, etiology, and associated anomalies, and are
      mainly based on proper casting (often repeated), bracing (often intermittent
      between casting) and proper respiratory equipment. From time to time, a surgical
      treatment is locally indicated, but most of the time results are disappointing
      and the best is to repeat non-surgical treatment until proper definitive
      arthrodesis can be performed. This approach is not very rewarding for the child
      and family, but is clearly better than sudden extensive surgery in early
      childhood with very severe and disastrous results in adulthood. It is our hope
      that the recommendations and thoughts presented in this paper will help readers
      to manage young children using the most efficient, non-aggressive, but long
      lasting therapy.

PMID- 16609623
TI  - [Genetics and orthopedics: genetic implications of congenital limb
      abnormalities].
AB  - Limb malformations are frequent. These malformations are isolated or associated
      with anomalies of other developmental fields and accurate diagnostic is essential
      for prognosis evaluation, treatment and genetic counseling. Animal embryology and
      molecular biology techniques, have given us a better understanding of the
      processes of growth and patterning of the limb buds. The key genes that are
      involved in these processes have been identified and their interactions
      recognized. Human genetics has been able to identify, or at least localize,
      several genes implicated in limb development. We here review the present
      knowledge on these genes and their mutations responsible for limb anomalies.

PMID- 16609625
TI  - [Prevention of thrombosis and vascular inflammation: importance of combined
      cyclooxygenase and 5-lipoxygenase inhibitors].
AB  - Aspirin, a standard non-steroidal anti-inflammatory drug (NSAID) is currently
      used in antithrombotic treatment. However, its use is limited by largely
      recognized gastrotoxicity and recommended doses are low. The major side effect of
      aspirin is related to its ability to suppress prostaglandin (PG) synthesis by
      constitutive cyclooxygenase-1 (COX-1). Specific inhibitors of COX-2, the
      inducible isoform of COX which was more recently described, have potent
      antiinflammatory effects. They are associated with minor risk of gastric tractus
      toxicity and reduced inflammatory leukocyte components known for their
      proatherothrombotic properties. Nevertheless, recent findings attributed a
      significant cardiovascular risk to some of them. 5-lipoxygenase (5-LOX), an
      enzyme mainly expressed by leukocytes, is responsible for the generation of
      leukotrienes, the major lipidic proinflammatory mediators. Development of
      combined inhibitors of 5-LOX and COX isoforms 1 and 2 inaugurate an interesting
      new therapeutic pathway. Indeed, such inhibitors suppress not only the activation
      of platelets, leukocytes and endothelial cells but also prevent their metabolic
      and functional interactions. In addition to their broad spectrum inhibition, they
      may be associated with the minor gastrotoxic effect. Thus, platelet-leukocyte
      interactions which dominate the underlying inflammatory process particularly in
      atherosclerosis, might reinforce the benefits of such inhibitors.

PMID- 16609626
TI  - [Heredity and genetic aspects of Raynaud's disease].
AB  - The pathophysiology of primary Raynaud's phenomenon (Raynaud's disease) remains
      uncertain but the transmission of this primary microcirculatory dysregulation
      seems strongly influenced by genetic factors. For a long time, physicians have
      found that the hereditary factor plays an important role in the genesis of
      Raynaud's disease. Familial analysis and twin studies have confirmed the role of
      an hereditary factor. It seems heterogeneous but pedigree analysis indicates the
      possibility of an autosomal dominant transmission influenced by sex, in some
      families, allowing an approach called "reverse genetic" based on linkage
      analysis. Such an approach has focused on few loci but sequencing of candidate
      genes for genetic mutations remains negative. Given the supposed heterogeneity of
      the genetic transmission of Raynaud's disease, diversification of strategies in
      molecular genetics is suitable with reference to techniques applied to
      multifactorial heredity.

PMID- 16609627
TI  - [Management of adults with essential hypertension--2005 update--guidelines].

PMID- 16609628
TI  - [Radiation arteritis- and radiodermitis-induced leg ulcer: surgical
      revascularization].
AB  - A forty-four-year old man was hospitalized for diagnosis and treatment of a left
      leg ulcer which did not heal despite good compliance with a three-month medical
      regimen. Twenty years before he had undergone surgical curettage and radiotherapy
      (81 gy) for an osteosarcoma of the upper third of the left tibia. He was
      considered completely cured with regular findings. On examination he had a 5 X 7
      cm deep ulcer with raised margins and no signs of infection, localized on the
      radiodermatitis on the medial aspect of his left leg. Arterial examination
      confirmed the left arteriopathy with absence of distal pulses; the Ankle Brachial
      Pressure Index was 0.69 and the foot TcPO2 27 mmHg. Arteriography confirmed the
      localized left lesions with three distal popliteal and proximal arterial
      occlusions, all other arteries being strictly normal. Arterial and dermatological
      radiation leg ulcer was retained as the etiological diagnosis. As the ulcer was
      very painful, extensive and limited walking distance, surgical revascularisation
      was undertaken because endoluminal revascularization was impossible. A
      femoroperoneal saphenous bypass was performed with surgical incisions beyond the
      radiodermatitis area. Two months after a split skin graft, the ulcer was
      considered healed and the patency of the by-pass confirmed on duplex examination.
      This is the first case report of a successful distal by-pass performed for
      radiation arteritis and ulcer healing. Long-term follow up should be reported.

PMID- 16609629
TI  - [Endovascular stent grafting for chronic proximal thoracic aortic
      pseudoaneurysm].
AB  - Chronic descending aortic pseudoaneurysm generally result from traumatic and can
      spontaneously progress to rupture. We report the case of a 70-year-old patient
      presenting a chronic pseudoaneurysm of the thoracic aorta treated by endovascular
      stent-grafting. The patient underwent imaging evaluation for endoluminal repair:
      thoracic aorta was evaluated by contrast-enhanced CT scan and supra-aortic and
      iliac vessels were evaluated by MRI-imaging. Stent-graft was deployed under
      fluoroscopic guidance across the aneurysmal defect. The left sub-clavian artery
      was covered, but no ischemic symptoms appeared and transposition of the left sub
      clavian artery was not necessary. Clinical and radiological follow-up at 6 and 30
      months showed total exclusion and thrombosis of the pseudoaneurysm. Chronic
      pseudoaneurysm of the thoracic aorta do benefit from endoluminal repair, which is
      adapted to patients with high surgical risk.

PMID- 16609630
TI  - [Disseminated tuberculosis and profound thrombopenia].
AB  - Thrombocytopenia within the context of disseminated tuberculosis can lead to
      complications requiring rapid treatment. Although the origin is generally
      central, thrombocytopenia can arise from an immune disorder. We hereby report a
      case of disseminated tuberculosis associated with thrombocytopenia, which
      required, in addition to antituberculosis therapy initiated before
      bacteriological proof, corticosteroid treatment and multiple platelet
      transfusions. The discovery of anti-platelet antibodies along with the success of
      immunomodulator therapy confirmed the auto-immune origin of this
      thrombocytopenia.

PMID- 16609633
TI  - [Comparison of two national food surveys (INCA 1 1998-99 and Health Nutrition
      Barometer 2002) with regard to five food recommendations of the National
      Nutrition and Health Program].
AB  - BACKGROUND: Monitoring the dietary intake of the French population requires the
      implementation and regular renewal of representative national survey. As these
      surveys can use different methodologies (food frequency questionnaire, 24 hour
      recall, 3 or 7-day dietary record...), it seems useful to check whether they
      supply similar results. The aim of this study is to determine whether two
      representative national surveys with different methodologies can be used
      alternately to monitor changes in food consumption of the French population.
      METHOD: Percentages of consumers aged 15-75 were compared between two national
      food surveys (Health Nutrition Barometer 2002 and INCA 1 1998-99) with respect to
      five food frequency recommendations of the French National Nutrition and Health
      Program. RESULTS: The same public health priorities were found in both surveys:
      the food groups were graded according to the same hierarchy of adequate food
      intake prevalences (ascending: fruits and vegetables, dairy products, fish,
      starchy foods and meat-fish-egg products). On the other hand, significant
      statistical different elements were pointed out in a few food groups which may be
      explained by methodological patterns. Definitions of portions and food groups,
      survey duration and seasons are indeed important parameters to be considered when
      comparing surveys. CONCLUSION: The results show the need to elaborate
      standardized methods for comparison of food consumption surveys, which can be
      useful for the evaluation of the national nutritional recommendations. The
      methodological limitations described in this study also indicate that the
      quantitative description of food intake trends should improve when established by
      the results of the same regularly repeated survey.

PMID- 16609634
TI  - Prospective evaluation of the impact of organizational change on perceived stress
      and health in assembly-line workers in an automobile plant.
AB  - BACKGROUND: Although the competitive climate of the automobile industry is
      modifying the organization of work in French plants, the health consequences of
      these changes have not been investigated. The objective of this study was to
      determine the health impact on employees of an automobile manufacturing plant in
      northern France of a change to a "Total Quality Management" type of organization.
      METHODS: This before-and-after study concerned 80 factory employees. The health
      impact of their work was measured before the change and then 4 and 12 months
      after the reorganization began, with a French version of the Job Content
      Questionnaire, which assesses stress at work, a self-rated health scale, and the
      rate of infirmary visits. Paired comparisons were used to assess before-and-after
      changes. RESULTS: Scores for psychological and physical demands increased
      significantly at 4 and 12 months after the organizational changes began, while
      the self-rated health score diminished significantly during both follow-ups.
      Decision latitude and social support scores remained unchanged during follow-up,
      and the number of subjects under stress in the study group (high psychological
      demands and low decision latitude) did not increase significantly. Finally, the
      rate of infirmary visits increased significantly during the study period.
      CONCLUSION: These results show that employees'reaction to these organizational
      modifications differed according to the scale studied and that their overall
      perceptions were more complex than expected in view of the changes that occurred.

PMID- 16609635
TI  - [Measles, pertussis, rubella and mumps completeness of reporting. Literature
      review of estimates for industrialized countries].
AB  - BACKGROUND: Surveillance data for infectious diseases in industrialized countries
      have been providing useful epidemiological information for several years.
      However, surveillance is complex and notifications underestimate the true disease
      incidence. The goal of this paper is to determine the completeness of reporting
      of measles, pertussis, rubella and mumps through notification in industrialized
      countries. METHODS: A thorough literature review of papers published (in French
      or English) on surveillance data of measles, pertussis, rubella and mumps was
      undertaken with PUBMED. The review was limited to studies conducted in
      industrialized countries that quantitatively assessed the completeness of the
      reporting of these diseases. RESULTS: Fourteen studies published from the 1920s
      met the inclusion criteria. For measles, the studies suggest that 64-85% of
      symptomatic patients sought medical care, 13-57% of those were diagnosed with
      measles and 22-81% of the diagnosed cases were reported for a completeness of
      reporting ranging from 7% to 63% between 1920 and 1980 and 3% to 41% in recent
      years. For pertussis, it was estimated that 49-59% of symptomatic patients sought
      medical care, 12% of those were diagnosed and 19-47% of the diagnosed cases were
      reported for a completeness of reporting ranging from 5% to 25% between 1920 and
      1980 and from 3% to 12% in recent years. Very few studies on rubella and mumps
      were found and none allowed the determination of the global completeness of
      reporting. CONCLUSION: Reporting has been found to be considerably incomplete.
      Continued efforts to improve the recognition and reporting of these diseases are
      needed.

PMID- 16609636
TI  - [Use of a directory of specialized services and guidance in the healthcare
      system: the example of the Orphanet database for rare diseases].
AB  - BACKGROUND: Orphanet is a database of rare diseases which includes a directory of
      services providing information on professional experts working either in
      laboratories offering diagnostic tests or in specialized outpatient clinics. The
      printed directory is sent to these experts, to all relevant hospital departments
      (public and private), healthcare authorities, and patient support groups. The
      directory is also available online (www.orpha.net). The aims of this study were
      (i) to determine how the directory is used to refer patients and send specimens,
      and (ii) to investigate its impact on patient referral. METHODS: Data were
      obtained from experts and patient support groups concerned with rare diseases, as
      well from non-expert health professionals and patients. Emphasis was placed on
      knowledge of the Orphanet database, use of the directory as a tool for referrals,
      opinion of users about the quality of the directory, and opinion of the
      referenced experts about its possible impact on their referrals. Four methods of
      data collection were used: (i) a postal questionnaire to all referenced experts;
      (ii) an on-line questionnaire posted for a few hours on the Orphanet Website that
      had to be completed to access the site; (iii) interviews with 25 of the
      referenced experts; (iv) interviews with 35 leaders of patient organizations.
      Data were analysed using the chi2 test and logistic regression. RESULTS: Response
      rates were good: 74% of laboratory experts (224/304) and 68% of clinicians
      (459/678) answered the questionnaire. The responders proved to be representative.
      Among those who responded, 85% of the laboratory experts and 80% of clinician
      experts used Orphanet. More than two-thirds of them used Orphanet to identify
      (other) laboratories to them send specimens, and (other) clinicians for patient
      referral. Some non-expert hospital-based clinicians had nearly the same use.
      Patient support groups also used the directory. Persons using the directory
      happened to know Orphanet in their professional environment. Conversely,
      patients, non-MDs healthcare professionals and professionals in private practice
      discovered Orphanet using search engines, often when searching information about
      a rare disease. Of those who had already accessed the directory, most (94%)
      consider that the quality of the lists was "good" or" rather good". Among the
      experts, 29% of laboratories and 9% of clinicians considered that Orphanet had an
      impact on their referrals. CONCLUSION: The Orphanet directory is used to refer
      patients and specimens, especially by experts and patient organizations. It
      appears to have more impact on referrals within the healthcare system for
      laboratories than for specialized outpatient clinics. The impact is strong when
      expertise in the field is very scarce.

PMID- 16609637
TI  - Geographic variations in probability of pregnancy in four cities of France.
AB  - BACKGROUND: Several studies have described geographic variations in human
      fecundability, but this phenomenon has almost exclusively been studied at an
      international level rather than within a given country. Our aim was to describe
      geographic variations in fecundability, the monthly probability of pregnancy,
      between four cities of France. METHODS: We conducted a cross-sectional study in
      four French maternity units from Toulouse, Rennes, Lyons and Paris, among
      partners of pregnant women. Women were asked about the time to pregnancy (TTP) of
      their current pregnancy. TTP was analysed with a discrete Cox model allowing to
      estimate fecundability ratios (FR). RESULTS: Time to pregnancy was defined for
      894 couples. There was no strong evidence of heterogeneity in fecundability
      between the four compared cities (p=0.05 without adjustment and p=0.25 after
      adjustment for behavioural and medical factors). The highest fecundability was
      observed in Rennes and the lowest in Toulouse (fecundability ratio (FR)=1.28, 95%
      CI: 1.01-1.63). Differences in fecundability were smaller between the other
      cities. CONCLUSION: We highlighted a possibly slightly higher fecundability in
      Rennes compared to Toulouse. Possible explanations for this finding are
      discussed. We note that the finding is consistent with previous observations
      indicating a higher sperm concentration among semen donors in Rennes than in
      Toulouse.

PMID- 16609638
TI  - Random-effect models for ordinal responses: application to self-reported
      disability among older persons.
AB  - BACKGROUND: Longitudinal studies with ordinal repeated outcomes are now
      widespread in epidemiology and clinical research. The statistical analysis of
      these studies combines two difficulties: the choice of the best ordinal model and
      taking into account correlations for within-subject responses. METHODS: Random
      effect models are of particular value in this context and we propose here a
      fitting strategy. The various ordinal models extended to the case of repeated
      responses are detailed. We explain how the choice of model constrains the random
      effect structure. Model selection criteria and goodness-of-fit measures are also
      presented. These issues are dealt with by using an example of self-reported
      disability in older women assessed annually over a period of seven years.
      RESULTS: The proportionality of the odds ratios was validated for the covariables
      "age" and "gait speed". In contrast the impact of the covariable "pain" differs
      according to the levels of disability. The restricted partial proportional odds
      model was found to have a goodness of fit equivalent to the full generalized
      ordered logit model while the stereotype model appeared to give poorer fit.
      CONCLUSIONS: The random-effects models presented in this paper allow taking into
      account the ordinal nature of the outcome in longitudinal studies. Furthermore
      the impact of the risk factors can be modeled according to the response levels.
      This approach can be useful for a better understanding of complex processes of
      evolution.

PMID- 16609639
TI  - [Directly observed therapy (DOT): from tuberculosis to HIV].
AB  - BACKGROUND: Combination antiretroviral therapy, which is the standard of care
      since 1996, has been demonstrated to be very effective in suppressing plasma
      viral load in patients infected with HIV. Optimal benefit from antiretroviral
      drugs, however, is obtained when the patient adheres strictly to the rigorous
      treatment regimen. For some patients it is difficult to obtain good adherence to
      antiretroviral regimens. In response to these concerns, different strategies,
      such as directly observed therapy, have been proposed to attempt to improve
      adherence to antiretroviral treatment. Directly observed therapy is a strategy
      that has its roots in the treatment of tuberculosis and it consists essentially
      of taking the medication in the presence of a health care provider or another
      designated person. This strategy has been recently tried in the treatment of HIV
      but its efficacy remains unknown. METHOD: A Medline and Medscape search was
      performed to review all pertinent publications on the use of directly observed
      therapy in HIV infection. RESULTS: Twenty-five papers published between 1996 and
      2004 were selected. Almost all the studies were performed in industrialized
      countries in North America and Europe. The majority of the studies are
      retrospective, six of them comparing at least two strategies (directly observed
      therapy vs standard of care). Only one randomized trial has been found. The
      patients involved in the studies are intravenous drug users or particularly non
      adherent patients. Almost all studies show a better rate of adherence or a better
      control of the viremia in patients on directly observed therapy. CONCLUSIONS: The
      directly observed therapy seems to be a valuable and feasible way to raise the
      adherence rate in HIV patients with a problem of non-adherence to antiretroviral
      treatments. Clinical trials are needed to evaluate the efficacy of this strategy
      to raise the adherence rate among patients who need additional support to take
      their antiretrovirals.

PMID- 16609640
TI  - [Trends in corpulence of young men on Reunion Island over a quarter century of
      westernization].

PMID- 16609645
TI  - [The ideal emergency department].

PMID- 16609646
TI  - [Management of adult abdominal pain in the Emergency Room].
AB  - Abdominal pain is a commonplace reason for surgical consultation in the emergency
      department and is the the most common symptom which the digestive surgeon on-call
      must evaluate. He must understand the pathophysiologic basis of visceral pain and
      referred pain in order to appreciate its diverse manifestations. Abdominal pain
      can stem from many causes intestinal and non-intestinal, medical and surgical.
      Evaluation and management in the emergency department must be rapid and
      pragmatic; clinical history and physical examination should define the gravity of
      the case, direct the first diagnostic procedures and complementary examinations,
      and guide the therapeutic direction. Ultrasonography is a quick and effective
      diagnostic procedure in the diagnosis of biliary, urologic, and gynecologic
      pathologies; it can be useful for other digestive problems as well. The new
      generation spiral CT scanner gives excellent definition of digestive and vascular
      pathologies. The initial evaluation and management of the acute abdomen may
      determine the prognosis of the patient; it should lead to prompt symptomatic
      relief and to a well-directed treatment appropriate to the diagnosis.

PMID- 16609647
TI  - [Indications for laparoscopy in general and gastrointestinal surgery. Evidence
      based recommendations of the French Society of Digestive Surgery].

PMID- 16609648
TI  - [Surgical approach to common bile duct strictures].

PMID- 16609649
TI  - [Enterocolpoplasty. Vaginal reconstruction using a transposed right colon
      segment].

PMID- 16609650
TI  - [Primary mesenteric volvulus].

PMID- 16609651
TI  - [A patient with angiocholitis].

PMID- 16609652
TI  - [Congress of the American College of Surgeons--San Francisco, October 16-20,
      2005].

PMID- 16609653
TI  - [Suprahepatic images. 1. Internal herniation by small bowel strangulation on
      perihepatic adherences].

PMID- 16609654
TI  - [Suprahepatic images. 2. An epigastric tumor in a young woman].

PMID- 16609655
TI  - [Childhood diencephalic pilocytic astrocytoma. A review of seven observations].
AB  - BACKGROUND AND PURPOSE: Pilocytic astrocytoma (PA) is a WHO grade I tumor of the
      central nervous system mostly arising in children and young adults. Management of
      diencephalic PA is a difficult challenge. Surgical treatment has to cope with
      both the difficulties of deep location and eloquent area tumors. MATERIALS AND
      METHODS: We retrospectively reviewed seven pediatric cases (female: 4, male: 3)
      of diencephalic PA. Opto-chiasmatic tumors were excluded from the series. Mean
      age at diagnosis was 108 months (9 years) (range: 4 month-18 years), median age
      was 111 months. Median follow-up for the series was 125 months. Tumor locations
      were as followed: right thalamus: 2, both thalami: 1, hypothalamus: 3, and right
      basal ganglia: 1. At the onset, the first symptom was mostly raised intracranial
      pressure. The delay in diagnosis ranged from 48 hours up to 6 years. TREATMENT: a
      shunting procedure was performed in 3 patients, a direct surgical approach in 5
      patients (gross total removal: 2; partial removal: 3) and one patient had only a
      biopsy. Three children were re-operated. Three patients were treated by
      radiationtherapy (RT) after surgery. Chemotherapy was delivered for 4 children.
      RESULTS: The overall survival rate was 71.4 months (almost 6 years) (range: 3-184
      months). Median survival rate was 42 months (3.5 years). Three children died, two
      by tumor progression and one death related to late side-effects of RT. Four
      patients have a good quality of life with GOS I (n = 3) or II (n = 1). We
      observed tumor regression in two patients at 1 and 17 years after the beginning
      of treatment. Correct diagnosis was only made for two cases at the initial
      pathological examination. CONCLUSION: The course of diencephalic PA is still
      unpredictable. The tumor can be controlled by a partial surgical removal, and a
      residual tumor can sometimes decrease in size after surgery. Gross total removal
      of these tumors, although difficult, may be performed. With cranial navigation
      systems, the risk is low. Pathological diagnosis is sometimes difficult to
      assess.

PMID- 16609656
TI  - [Subthalamic deep brain stimulation for severe idiopathic Parkinson's disease.
      Location study of the effective contacts].
AB  - The subthalamic nucleus (STN) is the main target of deep brain stimulation (DBS)
      treatment for severe idiopathic Parkinson's disease. But there is still no clear
      information on the location of the effective contacts (used during the chronic
      phase of stimulation). Our aim was to assess the anatomical structures of the
      subthalamic area (STA) involved during chronic DBS. Ten patients successfully
      treated were included. The surgical procedure was based on direct STN targeting
      (stereotactic MRI based) pondered by the acute effects of intraoperative
      stimulation. We used a formaldehyde-fixed human specimen to compare by matching
      MRI images obtained at 1.5 Tesla (performed in clinical stereotactic conditions)
      and at very high field at 4.7 Tesla. This allowed accurate analysis of the
      anatomy of the STA and retrospective precision of the location of the center of
      effective contacts which were located within the STN in 4 patients, at the
      interface between the STN and the ZI and/or FF in 13, at the interface between ZI
      and FF in 2 and between the STN and the substantia nigra in one. These results
      were consistent with the literature, revealing the implication of neighboring
      structures, especially the zona incerta and Forel's Field, in the clinical
      benefit.

PMID- 16609657
TI  - [The WSH percutaneous spine fixation device. Actual results and future
      expectations].
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to report our initial
      experience with a new percutaneous spine fixation system, avoiding open exposure,
      excessive blood loss and extensive muscle dissection. With the specially designed
      plates, this system can be used whatever the conformation of the segment
      instrumented is kyphotic or lordotic. METHODS: Sixteen patients (9 men and 7
      women ranging in age from 27 to 78 years, mean 54.9) underwent percutaneous
      pedicle fixation using this device. Twelve patients underwent single level
      fusions (discogenic lowback pain in 6 cases, spondylolisthesis in 1), and 4
      underwent two-level fusions (2 for lumbar fracture and 2 for spondylolisthesis).
      TLIF by intersomatic cages were inserted at the same time in two patients with
      spondylolisthesis. The follow-up period ranged from 3 to 15 months (mean 5
      months). RESULTS: Improvement in pain control was assessed using a specially
      designed scale, allowing qualitative self-evaluation of pain control. Pain
      control was excellent in 12 patients, good in 3 and poor in one case due to loss
      of independence related to multiple associated disabling conditions. CONCLUSIONS:
      Percutaneous pedicule screw insertion using this device is a safe and reliable
      technique. Further improvements in the system which allows a certain degree of
      spinal mobility after screw placement are in process. Early results shown in this
      study illustrate the perspectives.

PMID- 16609658
TI  - [Intracranial facial nerve schwannomas. Seven cases reviewed].
AB  - BACKGROUND AND PURPOSE: Intracranial facial nerve schwannomas are rare neoplasms.
      Preoperative diagnosis is difficult because of non-specific clinical
      presentations (deafness, facial paralysis sudden or progressive) and radiological
      differential diagnosis (petrous bone tumor, vestibular schwannoma). Treatment
      depends on localization and has to be discussed for each case. METHODS: Seven
      cases (four men and three women) of intracranial facial nerve schwannomas were
      retrospectively studied. RESULTS: Before treatment, we found deafness in six
      cases (two sudden and four progressive), a facial palsy in five cases (three
      sudden and two progressive). Five patients had deafness and facial palsy. One
      patient had only headache. Three schwannomas were supra and intra-petrous, two in
      the cerebello-pontine angle, and two were plurifocal (petrous bone, internal
      auditive canal and cerebellopontine angle). Six patients were operated on with an
      oto-neurosurgical procedure. After treatment, facial palsy always worsened
      (requesting secondary hypoglosso-facial anastomosis in cinq cases). Only one case
      of transmission deafness improved after ossiculoplasty. One patient is still
      under clinical and radiological observation. CONCLUSION: Diagnosis is difficult
      and made operatively in half of patients. A large tumor requires surgery, but
      surveillance can be a good option for a small one, considering the risk of
      postoperative facial palsy.

PMID- 16609659
TI  - [Idiopathic acute obstructive hydrocephalus. Case report].
AB  - Acute hydrocephalus is rarely encountered in adults without venticuloperitoneal
      or venticuloatrial shunts. The purpose of this report is to describe a case of
      acute hydrocephalus due to no identifiable cause. A 40-year-old man developed a
      typical clinical picture of intracranial hypertension within a 24-hours period.
      On the morning of hospitalization, the patient consulted his physician for severe
      headache followed quickly by nausea and vomiting. After cerebral CT-scan, the
      patient was referred to our department. His condition rapidly worsened, with
      confusion, then drowsiness. Magnetic resonance imaging (MRI) demonstrated quadri
      ventricular hydrocephalus with a Chiari I malformation. In view of his rapidly
      deteriorating clinical condition, emergency endoscopic third ventriculostormy was
      performed. The patient recovered rapidly and was discharged 8 days after the
      procedure. Diagnostic work-up included lumbar puncture showing normal
      cerebrospinal fluid (thereby eliminating multiple sclerosis, low-grade
      intracranial hemorrhage, and meningitis (bacterial, viral, fungal)), spinal MRI
      depicting no medullary lesions, and brain angiography revealing no vascular
      abnormalities. Follow-up brain MRI carried out at six months after
      hospitalization demonstrated normal ventricles and complete disappearance of the
      Chiari I malformation. No conclusion can be drawn as to whether the Chiari I
      malformation was the consequence or cause of hydrocephalus. The explanation of
      this acute hydrocephalus is the acute decompensation without identifiable cause
      of idiopathic stenosis of the foramen of Magendie and Luschka. Treatment with
      endoscopic third ventriculostomy is effective.

PMID- 16609660
TI  - [Terminovertebral aneurysm arising from basilar artery fenestration].
AB  - A case of ruptured middle saccular aneurysm arising from basilar artery
      fenestration is reported. Defects of the medial wall at the junctures of the
      fenestrated segments explain the association between vertebrobasilar aneurysms
      and basilar artery fenestration. A 47 year-old woman had a perimesencephalic
      subarachnoid hemorrhage. Immediate angiography revealed a ventral vertebrobasilar
      aneurysm and an endovascular coil occlusion was performed. Embryological
      development, pathogenesis and therapeutic difficulties are discussed.

PMID- 16609661
TI  - [Aneurysmal bone cyst of the cranial base treated by partial resection and
      calcitonin injection. A case report].
AB  - STUDY DESIGN: First published report of a cranial aneurysmal bone cyst (ABC)
      treated successfully with intralesional injection of calcitonin. OBJECTIVES: To
      describe a safe and effective treatment method for ABCs of the cranial base.
      SUMMARY OF BACKGROUND DATA: ABC is a rare form of dystrophic pseudotumor. Less
      than 100 cases involving the skull have been reported in the literature, most of
      them localised in the cranial vault. Cranial base locations are rare and
      difficult to treat. We selected this treatment after a very rapid recurrence of
      the lesion following a partial resection. Method. - After a partial resection of
      a 10 cm petro-occipital ABC that encased the vertebral artery and the lower
      cranial nerves, an Ommaya reservoir was implanted with a catheter tip inside the
      ABC. Repeated intralesional injections of calcitonin were performed through the
      reservoir. RESULTS: Shrinkage of the cyst occurred with disappearance of its
      heterogeneous cystic content and ossification of its walls. There was no
      complication and the lesion remains quiescent at a 3 year follow-up. CONCLUSION:
      We reviewed the pertinent literature concerning percutaneous treatment of ABC.
      The percutaneous intralesionnal injection of calcitonin was reported in the
      literature only in 3 publications reporting 9 cases that did not involve the
      skull. This treatment seems safe and effective, worthy in cranial base ABCs that
      are difficult to resect completely.

PMID- 16609663
TI  - [Address to the Society of Laryngology of the Paris Hospitals, January 15, 2005].

PMID- 16609662
TI  - [Vermian epidermoid cyst revealed by head injury].
AB  - Vermian epidermoid cyst developing in the fourth ventricle is very rare. We
      report a case observed in a 24-year-old man, who presented severe headache,
      dizziness and a blurred vision following head injury. Examination revealed a
      discrete gait disturbance. Cerebral CT-scan showed a large hypodense lesion of
      the posterior fossa without contrast enhancement. MRI demonstrated the vermian
      location of this lesion which displaced the roof of the fourth ventricle upward
      and the brainstem forward. A suboccipital approach allowed total removal of a
      well-encapsulated epidermoid cyst, non adherent to the floor of the fourth
      ventricle. The postoperative course was uneventful.

PMID- 16609664
TI  - [Facial paralysis after temporal bone trauma].
AB  - OBJECTIVES: To evaluate functional outcome in 64 cases of facial paralysis
      following temporal bone fracture and discuss decisive arguments leading either to
      medical treatment or surgical management. METHODS: Sixty-four patients suffering
      from post-traumatic facial paralysis were managed between 1995 and 2003: 38 (59%)
      were given medical treatment and 26 (41%) underwent surgery. A combined middle
      fossa and transmastoid approach was mostly used (58%). Electrophysiological
      testing and CT scan results were the main points of the decision algorithm.
      RESULTS: Electroneuromyography seems to be the most accurate exploration for
      guiding treatment. Good results (grades I to II on the House and Brackmann scale)
      were obtained in 63% of cases after medical management and in 39% of cases after
      surgical treatment. Grades III or IV were obtained in 13% of medically-treated
      patients and 42% of surgically-treated patients. CONCLUSION: Management of facial
      paralysis following temporal bone fracture in accordance with
      electrophysiological testing (evoked EMG) together with CT scan findings enabled
      accurate indications for surgical treatment. A good grade I or II result can be
      expected after medical management. A grade III is at best reached after nerve
      anastomosis.

PMID- 16609665
TI  - [Contribution of 18-F-FDG PET for detection of head and neck carcinomas with an
      unknown primary tumor].
AB  - OBJECTIVES: To evaluate the usefulness of fusioning positron emission tomography
      with computed tomography (PET/CT) for the detection of head and neck carcinomas
      of unknown primary. METHODS: This prospective study included 20 patients with
      cervical lymph node of squamous cell carcinoma of unknown primary after standard
      initial workup (nasofibroscopy and CT scan of the chest and head and neck).
      Patients underwent PET/CT and panendoscopy of the upper airways and upper
      digestive tract with PET/CT directed biopsies. The follow-up was 6 months minimum
      in all patients. RESULTS: A potential primary tumor was found in 10 of the 20
      cases and confirmed by histology in 7 cases (3 bases of tongue, 1 tonsillar
      pillar, 1 vallecula, 1 tonsillar fossa, 1 piriform sinus). Four of these seven
      patients presented a normal endoscopy (diagnosis was made with submucosal PET/CT
      directed biopsies). PET/CT was normal in 10 of 20 cases with 3 false negatives.
      The sensitivity of PET/CT was 70%, the specificity was 70% and the accuracy was
      70%. CONCLUSION: PET/CT seems to be of interest in the detection of head and neck
      carcinoma of unknown primary. PET/CT detected 15% of unknown primary tumors with
      treatment-related implications.

PMID- 16609666
TI  - [Maxillary sinus cancers: Prognosis and quality of life: a retrospective study of
      22 cases].
AB  - OBJECTIVES: Maxillary sinus cancer is uncommon. We present a study of 22 cases of
      patients managed at the Nantes University Hospital for maxillary sinus cancer
      during the time period 1989-2002. MATERIALS AND METHODS: Clinical and oncological
      characteristics of the tumors were evaluated. Treatment and results were
      evaluated in association with the patients' quality of life, estimated with a
      questionnaire survey sent to surviving patients. RESULTS: Carcinomas predominated
      (68%). The TNM classification was: T2: 45.5%, T3: 45.5% and T4: 9%. 89% of necks
      were N0 and 9% were N1. Treatment course (determined after imaging) was surgical
      removal of the tumor by total maxillectomy: 77.5%; partial maxillectomy: 22.5%,
      associated with post-operative radiotherapy. Esthetic consequences and
      disabilities of patients assessed by the questionnaire pointed out that 68% of
      them were complaining of poor quality of life. Global survival at 12 months was
      63%, 20% at 24 months and 9% at 5 years. There were no statistically significant
      differences between specific survivals according to T-stage nor according to
      histological features. The difference was significant when surgical removal of
      the tumour was large according to post-operative histology. CONCLUSION: Authors
      conclude that maxillary sinus cancers exhibit poor prognosis, and focus on the
      necessity of quality of life assessment.

PMID- 16609667
TI  - [Differenciated thyroid carcinomas with laryngo-tracheal invasion].
AB  - OBJECTIVES: Analyze the diagnosis and treatment of differentiated thyroid
      carcinomas with laryngo-tracheal invasion. MATERIALS AND METHODS: Among the 117
      patients operated for a differentiated thyroid carcinoma in the ENT department of
      Tours Hospital (France) between January 1990 and December 2003, seven presented
      laryngo-tracheal invasion and were included in this retrospective study. RESULTS:
      Laryngo-tracheal resection resulted in a thyroid cartilage-shaving in two
      patients. We performed a resection of one side of the thyroid cartilage in one
      patient, a thyro-tracheal resection-anastomosis with a partial cricoidectomy in
      one patient, a partial vertical laryngectomy extended to the first tracheal ring
      in one patient and a total laryngectomy in one patient. No laryngo-tracheal
      resection was done in one patient. Early complications were swallowing disorders
      (n = 2), transitory hypoparathyroidism (n = 1), definitive recurrent nerve
      paralysis (n = 2), subcutaneous emphysema and hematoma (n = 1) and Claude Bernard
      Horner's syndrome (n = 1). Locoregional recurrences (n = 2) and distant
      metastasis (n = 2) were discovered six months to four years after the laryngo
      tracheal resection. With a mean follow-up of 40 month, four patients were alive
      (two disease free) two patients had died and one was lost of follow-up at three
      months. CONCLUSION: The frequency of locoregional recurrences and distant
      metastasis is higher for the differentiated thyroid carcinomas with laryngo
      tracheal invasion than the others. In these cases, we performed macroscopic
      carcinological surgery preserving laryngeal functions as much as possible.

PMID- 16609668
TI  - [How to perform laryngeal nasofibroscopy in adults].

PMID- 16609669
TI  - [Who am I: A...].

PMID- 16609670
TI  - Distributions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate
      (PFOS) in Japan and their toxicities.
AB  - Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are end
      products of many fluorochemical compounds in the natural environment. The aim of
      this review is to summarize several studies in Japan and characterize the
      toxicities of these compounds. We also compared the levels of contamination with
      those reported from various countries to illustrate the unique situation of the
      toxicological issues within Japan. PFOA and PFOS concentrations in surface water
      in Japan are in the ranges of 0.1-67,000 ng/L and 0.1-526 ng/L, respectively.
      While the origin of PFOS in surface water remains unknown, PFOA present in
      surface water is very likely to have been released from a few industries. The
      levels of PFOA and PFOS in the atmosphere are 71.8-919 pg/m3 and 2.3-21.8 pg/m3,
      respectively. The concentrations of PFOA and PFOS in Japanese serum range from an
      undetectable level to 52.2 ng/ml and from 0.2 to 57.7 ng/ml, respectively. The
      levels of PFOA and PFOS present in the serum of the inhabitants of Kyoto are
      higher than those of other cities. One epidemiological study conducted by 3M
      revealed an increase in prostate cancer mortality [3.3-fold increase (95% CI,
      1.02-10.6)] among workers exposed to PFOA. Another study conducted by 3M revealed
      an increase in bladder cancer mortality (SMR 12.77, 95% CI 2.63-37.35) among
      workers exposed to PFOS. PFOA and PFOS had a low order of toxicity in an acute
      toxicity study in rodents; however, they exhibited versatile toxicities in
      primates. Both chemicals are carcinogenic in rodents, causing reproductive
      toxicity, neurotoxicity, and hepatotoxicity. Additionally, peroxisome
      proliferation and calcium channel modulation are demonstrated effects. There are
      large interspecies differences in toxicokinetics.

PMID- 16609671
TI  - Hydroxylated polychlorinated biphenyls (OH-PCBs): recent advances in wildlife
      contamination study.
AB  - The exposure of wildlife and human population to environmental hazardous
      contaminants has been of global concern for over several decades. More recently,
      focus has been directed towards potential toxicological effects such as the
      endocrine disrupting function of xenobiotics. The hydroxylated metabolites of
      PCBs (OH-PCBs) should be pointed out as these compounds. OH-PCBs have emerged as
      important classes of environmental contaminants in wildlife and humans because of
      their ability to bind with the thyroxin transport protein, transthyretin (TTR),
      and their interaction with thyroid hormone receptors. However, data on their
      occurrence in wildlife and their behavior in the matrices of environment are
      limited. Topics include the formation of OH-PCBs, their physicochemical
      properties (octanol-water partition coefficient, Kow), analytical procedures and
      contamination status in wildlife. The guidance for improving the study of OH-PCB
      contamination is also briefly mentioned.

PMID- 16609672
TI  - Occurrence and origin of mutagenicity in soil and water environment.
AB  - Surface soil and surface water are repositories of chemicals released into the
      environment, and contaminations of surface soil and river water with mutagens
      were first reported in the 1970s. However, the identity of major mutagens in
      surface soil and river water remained unclear for more than two decades.
      Recently, we have identified some nitrated polycyclic aromatic hydrocarbons
      (nitro-PAHs), e.g., dinitropyrene isomers and 3-nitrobenzanthrone, as major
      mutagens in the organic extracts of surface soil that showed strong
      mutagenicities toward Salmonella typhimurium TA98 in the absence of a mammalian
      metabolic system (S9 mix), using a bioassay-directed fractionation method.
      Moreover, we identified new potent mutagens from substances adsorbed on a blue
      cotton (blue rayon) from river water samples, which showed strong mutagenicity
      toward S.typhimurium YG1024 with or without the S9 mix. One group was the
      phenylbenzotriazole (PBTA)-type mutagens, which were detected in river water
      samples collected at sites below textile dyeing factories. The other group has a
      dichlorobiphenyl skeleton, i.e., 4-amino-3,3'-dichloro-5,4'-dinitrobiphenyl, and
      was isolated from a river water sample contaminated with effluent from chemical
      plants treating polymers and dye intermediates. Some of the nitro-PAHs detected
      in surface soil, such as PBTA-type mutagens, and 4-amino-3,3'-dichloro-5,4'
      dinitrobiphenyl are novel compounds. Up to approximately 50% of the total
      mutagenicity of extracts from surface soils and river waters was accounted for by
      nitro-PAHs, PBTA-type mutagens, or 4-amino-3,3'-dichloro-5,4'-dinitrobiphenyl.
      However, major mutagens in most types of surface soil and river water with high
      mutagenicity remain unknown. Because environmental mutagens may play some role in
      the development of diseases such as cancer, their identification is an important
      step for understanding the risks to indigenous biota and human health. Further
      effort to identify these major mutagens must be made.

PMID- 16609673
TI  - Fate and partitioning of selected pharmaceuticals in aquatic environment.
AB  - Two nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and acetaminophen, a
      beta-blocker atenolol, and an antidepressant fluoxetine were selected, and their
      sorption coefficients (Koc values) on the basis of dissolved organic matter (DOM)
      and model sediments were determined. The highest values were found for fluoxetine
      for both DOM and sediments, followed by atenolol or ibuprofen. These Koc values
      were comparable to those of pyrene and 17beta-estradiol, a nonpolar four-ring
      polycyclic aromatic hydrocarbon and a polar natural estrogen, respectively. For
      these four pharmaceuticals, partition coefficients between synthetic membrane
      vesicles (liposomes) and water (Klipw values), and removal efficiencies for a
      simple batch activated sludge treatment were also determined. The highest Klipw
      values were again found for fluoxetine followed by atenolol. The removal
      efficiency for a 6-hour batch activated sludge treatment was over 90% for the two
      NSAIDs whereas that for atenolol was as low as 10%; both agreed with the results
      obtained in conventional studies, which showed the concentration in the influent
      and effluent of sewage treatment plants. The removal efficiency for fluoxetine
      was also over 90%, but it was sorbed by sludge and not biodegraded.

PMID- 16609674
TI  - Occurrence and fate of anti-inflammatory drugs in wastewater treatment plants in
      Japan.
AB  - The fates of anti-inflammatory drugs (e.g., ibuprofen, naproxen, mefenamic acid
      and ketoprofen), which are frequently detected in the discharges of wastewater
      treatment plants (WWTPs) and river water in Japan, were clarified in two WWTPs.
      The concentrations of ibuprofen, naproxen, mefenamic acid and ketoprofen were 69
      1080, 179-305, 143-1580 and 160-1060 ng/L in the influent, and N.D. (< 40 ng/L),
      74-166, 72-265, 64-107 ng/L in the effluent, respectively. The concentrations of
      the anti-inflammatory drugs analyzed were almost equal to or lower than those
      reported in foreign countries. High removal efficiencies of the drugs, except
      ibuprofen, were observed in the WWTP that has longer hydraulic retention time
      than that of the other WWTP. For ibuprofen, high removal efficiencies were
      observed in both WWTPs (84 to 98%). Disinfection by chlorination was not
      effective to remove the drugs surveyed. On the other hand, the effective removal
      of ketoprofen by ultraviolet (UV) radiation for disinfection was demonstrated,
      although the disinfection by-products were not identified.

PMID- 16609675
TI  - Prediction of systemic concentrations of sensitizing compound using TKTD
      simulation model.
AB  - To investigate the safe handling of an industrial product, phenyl vinyl sulfone
      (PVS), which has an extremely high potential for dermal sensitization at low
      concentrations and positive mutagenicity, the maximum no-effect concentration for
      dermal deposits was obtained from dermal sensitization experiments. The systemic
      concentrations in the liver, which is considered to be a target tissue of
      mutation, were monitored using the TKTD (Toxico Kinetics Toxico Dynamics) model
      by inputting the maximum no-effect concentration of sensitization. The predicted
      highest concentration in the liver was compared with the no-effect level of
      mutation in the same tissue, which was derived from an in vitro mutagenicity
      study. The results showed that when this product is handled at lower
      concentrations, which may not induce dermal sensitization, the systemic
      concentrations would be lower than those causing mutation in the liver. In
      workplaces, conditions that prevent dermal sensitization caused by PVS could also
      protect against the mutagenicity of this compound.

PMID- 16609676
TI  - Pathogenic IgA in IgA nephropathy: still the blind men and the elephant?
AB  - IgA nephropathy (IgAN), the most common glomerulonephritis worldwide, remains an
      important cause of end-stage renal failure. The pathology is characterized by
      mesangial deposition of IgA. The disease is now recognized as arising from
      anomalies of the IgA molecule and the kidneys are innocent bystanders. The
      immunochemical nature of the IgA molecule and its mesangial uptake command a
      pivotal role in the pathogenesis of IgAN.

PMID- 16609677
TI  - Arteriolar remodeling in essential hypertension: are connective tissue growth
      factor and transforming growth factor involved?
AB  - Gomez-Garre et al. report increased expression of connective tissue growth factor
      and transforming growth factor-beta and worsening of remodeling in subcutaneous
      arterioles of patients with essential hypertension during amlodipine treatment.
      Losartan improves remodeling without changes in cytokine expression. The
      discordant effects of two well-accepted treatments for hypertension underline the
      need for further studies on therapy-induced changes in arteriolar remodeling.

PMID- 16609678
TI  - ACE inhibition and glomerular repair: restructuring or regeneration?
AB  - In this issue of Kidney International, Andrea Remuzzi et al. convincingly
      demonstrate glomerular repair in spontaneous renal disease by ACE inhibition.
      These findings provoke questions about how ACE inhibition (or AT1R blockade) can
      on the one hand actually repair some diseased kidneys while on the other
      interfering with normal renal development or the recovery of other diseased
      kidneys.

PMID- 16609679
TI  - The future of hemodialysis membranes.
AB  - Hemodialytic treatment of patients with either acute or chronic renal failure has
      had a dramatic impact on the mortality rates of these patients. Unfortunately,
      this membrane-based therapy is still incomplete renal replacement, as the
      mortality and morbidity of these patients remain unacceptably high. Much progress
      must be made to improve the biocompatibility of hemodialysis membranes as well as
      their hydraulic and permselective properties to remove small solutes and 'middle
      molecules' in compact cartridges. The next directions of development will
      leverage materials and mechanical engineering technology, including microfluidics
      and nanofabrication, to further improve the clearance functions of the kidney to
      replicate glomerular permselectivity while retaining high rates of hydraulic
      permeability. The extension of membrane technology to biohybrid devices utilizing
      progenitor/stem cells will be another substantive advance for renal replacement
      therapy. The ability to not only replace solute and water clearance but also
      active reabsorptive transport and metabolic activity will add additional benefit
      to the therapy of patients suffering from renal failure. This area of
      translational research is rich in creative opportunities to improve the unmet
      medical needs of patients with either chronic or acute renal failure.

PMID- 16609680
TI  - PAX2 inactivation enhances cisplatin-induced apoptosis in renal carcinoma cells.
AB  - Renal cell carcinoma (RCC) is the most common kidney malignancy and has a poor
      prognosis owing to its resistance to chemotherapy. RCC cells overexpress the
      transcription factor, PAX2, normally expressed in fetal kidney but downregulated
      at birth. Since Pax2 suppresses apoptosis during renal development, we reasoned
      that PAX2 may confer resistance to cisplatin-induced apoptosis in RCC. Here, we
      show that PAX2 confers resistance to cisplatin-induced apoptosis in normal kidney
      cells and fetal kidney explants. Human embryonic kidney 293 cells transfected
      with a PAX2 expression vector and exposed to cisplatin (40 microM) exhibited 45
      +/- 15% as much caspase-3 cleavage compared to control cells. Conversely, murine
      collecting duct cells stably transfected with PAX2 antisense cDNA had twofold
      increase in cisplatin-induced apoptosis. Murine fetal (embryonic day 15) kidney
      explants from PAX2(1Neu)+/- mice exposed to cisplatin (25 microM x 24 h) had 50%
      increased apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labelling staining). We then show that RCC cells (CAKI-1 (human, Caucasian,
      kidney, carcinoma) and ACHN (human, Caucasian, kidney, adenocarcinoma)) express
      PAX2 protein. PAX2-small interfering RNA (100 nM) reduces endogenous PAX2 protein
      (10% of baseline) and induces apoptosis (Annexin-V staining). Pax2 knockdown
      sensitized RCC cells to cisplatin-induced apoptosis, killing 50-60% of cisplatin
      resistant ACHN and CAKI-1 cells. These findings suggest that PAX2 confers
      resistance to cisplatin-induced apoptosis in non-transformed kidney cells and
      fetal kidney explants. Similarly, Pax2 overexpression in RCC cells contributes to
      cisplatin resistance. Conceivably, a therapeutic strategy that inactivates Pax2
      in vivo might enhance the efficacy of conventional cytotoxic drugs against RCC.

PMID- 16609681
TI  - Mitochondrial dysfunction in focal segmental glomerulosclerosis of puromycin
      aminonucleoside nephrosis.
AB  - Focal segmental glomerular sclerosis (FSGS) is a major renal complication of
      mitochondrial (mt) cytopathies. The present study was designed to investigate the
      possibility of mtDNA lesion accumulation in podocytes, which are a primary
      pathogenic site of FSGS, during the development of glomerulopathy in puromycin
      aminonucleoside nephrosis (PAN). Two renal pathological phases of PAN, nephrosis
      phase and FSGS phase were studied. We investigated the expression of mt proteins,
      the copy number of a 4834 base-pair deletion (del-mtDNA), and total mtDNA content
      by real-time polymerase chain reaction, as well as the mRNA expression levels of
      the mt transcription factor A (mtTFA) and the nuclear respiratory factor-1 (NRF
      1) in glomeruli. The mtDNA encoded cytochrome c oxidase subunit I (COX I) protein
      level was identical to control in nephrosis phase, however, a 45% reduction was
      seen in FSGS phase. Intraglomerular del-mtDNA was 16-21 times higher than
      controls in both phases, but the proportion of this mutation was <1% of total
      mtDNA. The copy number of total mtDNA at nephrosis phase increased up to 241%,
      whereas, it decreased to 34% at FSGS phase in glomeruli. The mRNA expression of
      both mtTFA and NRF-1 was upregulated at nephrosis phase, but mtTFA was
      downregulated at FSGS phase. A reduction in mtDNA copy number resulted in reduced
      levels of COX I in glomeruli at FSGS phase, suggesting that mt dysfunction by
      mtDNA depletion potentially plays a key role in the pathogenesis of FSGS in PAN.

PMID- 16609682
TI  - Blood pressure and urinary sodium excretion in relation to the A-1984G
      adrenomedullin polymorphism in a Chinese population.
AB  - Adrenomedullin (ADM) is a vasodilator and inhibits salt appetite. An A-to-G
      substitution at position -1984 in the promoter region of the ADM gene likely
      increases transcription. We therefore investigated this polymorphism in relation
      to blood pressure and urinary sodium in a Chinese population. We genotyped 427
      Chinese enrolled in a family-based population study. We measured blood pressure
      by conventional sphygmomanometry and ambulatory monitoring. The frequencies of
      the ADM AA, AG, and GG genotypes were 50.6, 38.2, and 11.2%, respectively. In
      adjusted analyses, G allele carriers, compared to AA homozygotes, had
      significantly lower conventional (45.3 versus 48.5 mm Hg, P = 0.004) and 24-h
      (42.6 versus 44.3 mm Hg, P = 0.03) pulse pressures and urinary sodium excretion
      (143.8 versus 159.4 mmol/day, P = 0.03). In parents, but not offspring, both
      systolic pressure and pulse pressure were significantly (P<0.01) lower in G
      allele carriers. The genotypic difference in sodium excretion was consistent
      across the age range. In 68 informative offspring, transmission of the G allele
      was associated with lower urinary sodium excretion (effect size, 40.1 mmol/day, P
      = 0.01). In 81 healthy volunteers, the plasma ADM concentration was 15.2% higher
      in GG homozygotes than in sex- and age-matched AA subjects (11.4 versus 9.9
      pmol/l, P = 0.10). In conclusion, in Chinese, the ADM -1984G allele is associated
      with lower sodium excretion and in older subjects also with lower systolic
      pressure and narrower pulse pressure.

PMID- 16609683
TI  - The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in
      chronic kidney disease.
AB  - Glomerular-derived proteins may activate tubular cells to express the macrophage
      directed chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2). Macrophages
      at interstitial sites have a central role in directing renal scarring. We have
      prospectively assessed the relationship between albuminuria, urinary MCP-1/CCL2,
      interstitial macrophage infiltration, in situ damage, and clinical outcomes in a
      large group of patients with chronic kidney disease. We studied 215 patients and
      quantified albumin-creatinine ratio (ACR), urinary MCP-1/CCL2, interstitial
      macrophage numbers, and in situ damage. ACR correlated with urinary MCP-1/CCL2
      (correlation 0.499; P<0.001), interstitial macrophage numbers (correlation 0.481;
      P<0.001), and index of chronic damage (correlation 0.363; P<0.001). Macrophage
      numbers closely correlated with in situ damage (correlation 0.755; P<0.001). By
      multivariate analysis ACR, urinary MCP-1/CCL2, and interstitial macrophage
      numbers were interdependent. By Kaplan-Meier survival analysis albuminuria,
      urinary MCP-1/CCL2, interstitial macrophages, and chronic damage predict the
      outcome. ACR, macrophage numbers, chronic damage, and creatinine independently
      predicted renal survival. The association of ACR with other variables was
      strongest in patients with less advanced disease states. There is a close
      association between albuminuria, urinary MCP-1/CCL2, and interstitial macrophage
      infiltration with in situ damage and clinical outcomes. These findings support
      the hypothesis that albuminuria triggers tubular MCP-1/CCL2 expression with
      subsequent macrophage infiltration. These processes may represent the dominant
      pathway for the progression of renal injury before the establishment of advanced
      renal scarring.

PMID- 16609684
TI  - A novel missense mutation of SLC7A9 frequent in Japanese cystinuria cases
      affecting the C-terminus of the transporter.
AB  - Cystinuria is caused by the inherited defect of apical membrane transport systems
      for cystine and dibasic amino acids in renal proximal tubules. Mutations in
      either SLC7A9 or SLC3A1 gene result in cystinuria. The mutations of SLC7A9 gene
      have been identified mainly from Italian, Libyan Jewish, North American, and
      Spanish patients. In the present study, we have analyzed cystinuria cases from
      oriental population (mostly Japanese). Mutation analyses of SLC7A9 and SLC3A1
      genes were performed on 41 cystinuria patients. The uptake of 14C-labeled cystine
      in COS-7 cells was measured to determine the functional properties of mutants.
      The protein expression and localization were examined by Western blot and
      confocal laser-scanning microscopy. Among 41 patients analyzed, 35 were found to
      possess mutations in SLC7A9. The most frequent one was a novel missense mutation
      P482L that affects a residue near the C-terminus end of the protein and causes
      severe loss of function. In MDCK II and HEK293 cells, we found that P482L protein
      was expressed and sorted to the plasma membrane as well as wild type. The
      alteration of Pro482 with amino acids with bulky side chains reduced the
      transport function of b(0,+)AT/BAT1. Interestingly, the mutations of SLC7A9 for
      Japanese cystinuria patients are different from those reported for European and
      American population. The results of the present study contribute toward
      understanding the distribution and frequency of cystinuria-related mutations of
      SLC7A9.

PMID- 16609685
TI  - Clinical benefit of enzyme replacement therapy in Fabry disease.
AB  - Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A (r
      halphaGalA) enhances microvascular globotriaosylceramide clearance and improves
      clinical symptoms in patients with Fabry disease. We evaluated whether these
      effects are translated into a long-term benefit of kidney and heart function. We
      did a single center, prospective, open label study in 26 patients with Fabry
      disease (one early death, follow-up in 25 patients). r-Alpha-GalA was
      administered in a dosage of 1 mg/kg body weight every second week. The effect of
      therapy on clinical end points (death, cardiac and cerebrovascular event, renal
      failure), cardiac and renal function monitored by Doppler echocardiography, 99Tc
      GFR, and proteinuria was investigated. After a mean treatment time of 23 +/- 8
      months, nine patients experienced 12 end points, including two deaths. All end
      points occurred in patients with impaired renal function (n = 16; GFR 71 +/- 17
      ml/min/1.73 m2). Despite ERT, renal function deteriorated to 60 +/- 23
      ml/min/1.73 m2 (P = 0.04) and left ventricular posterior wall thickness (PWT) did
      not change (14.0 +/- 2.1 vs 13.4 +/- 2.3 mm). In contrast, patients without
      impairment of renal function (n = 9) had a more favorable outcome (no clinical
      events; GFR 115 +/- 18 vs 102 +/- 14 ml/min/1.73 m2, NS; PWT 11.7 +/- 1 and
      10.7+/-0.7 mm, P = 0.04). Proteinuria remained unchanged (1.34 +/- 0.94 vs 1.01
      +/- 0.97 g/day, n = 10). Patients with impaired renal function have a less
      favorable outcome and may develop cardiovascular and renal end points despite
      ERT.

PMID- 16609686
TI  - Longer treatment time and slower ultrafiltration in hemodialysis: associations
      with reduced mortality in the DOPPS.
AB  - Longer treatment time (TT) and slower ultrafiltration rate (UFR) are considered
      advantageous for hemodialysis (HD) patients. The study included 22,000 HD
      patients from seven countries in the Dialysis Outcomes and Practice Patterns
      Study (DOPPS). Logistic regression was used to study predictors of TT > 240 min
      and UFR > 10 ml/h/kg bodyweight. Cox regression was used for survival analyses.
      Statistical adjustments were made for patient demographics, comorbidities, dose
      of dialysis (Kt/V), and body size. Europe and Japan had significantly longer (P <
      0.0001) average TT than the US (232 and 244 min vs 211 in DOPPS I; 235 and 240
      min vs 221 in DOPPS II). Kt/V increased concomitantly with TT in all three
      regions with the largest absolute difference observed in Japan. TT > 240 min was
      independently associated with significantly lower relative risk (RR) of mortality
      (RR = 0.81; P = 0.0005). Every 30 min longer on HD was associated with a 7% lower
      RR of mortality (RR = 0.93; P < 0.0001). The RR reduction with longer TT was
      greatest in Japan. A synergistic interaction occurred between Kt/V and TT (P =
      0.007) toward mortality reduction. UFR > 10 ml/h/kg was associated with higher
      odds of intradialytic hypotension (odds ratio = 1.30; P = 0.045) and a higher
      risk of mortality (RR = 1.09; P = 0.02). Longer TT and higher Kt/V were
      independently as well as synergistically associated with lower mortality. Rapid
      UFR during HD was also associated with higher mortality risk. These results
      warrant a randomized clinical trial of longer dialysis sessions in thrice-weekly
      HD.

PMID- 16609687
TI  - Associations of hemodialysis dose and session length with mortality risk in
      Australian and New Zealand patients.
AB  - The optimal combination of hemodialysis (HD) dose and session length remains
      uncertain, and previous studies have not conclusively shown session length to be
      an important independent determinant of patient mortality. The objective of this
      study was to examine associations between HD dose and session length with
      mortality risk using data from the Australian and New Zealand Dialysis and
      Transplant Registry. Analyses were performed using a prospective inception cohort
      comprising all incident adult patients treated by thrice-weekly maintenance HD,
      who commenced renal replacement therapy with HD between 1 April 1997 and 31 March
      2004. In all, 6593 patients were identified, of whom 4193 had sufficient data for
      multivariate analyses. HD dose (single pool fractional clearance of urea, Kt/V)
      and session length were included in analyses as those recorded 12 months after HD
      inception to reduce confounding by residual renal function. The outcome examined
      was patient mortality. Survival analyses included Kaplan-Meier calculations of
      survival and Cox regression for multivariate analyses. Covariates in Cox models
      included patient demographics, co-morbid medical conditions at HD inception, and
      HD operating parameters. After adjustment for covariates and each other, Kt/V of
      1.30-1.39 and session length of 4.5-4.9 h were associated with the lowest
      mortality risk. There was no interaction between HD dose and session length.
      Thus, the optimal combination for mortality appears to be Kt/V of > or = 1.3 and
      session length of > or = 4.5 h. These data suggest a randomized controlled trial
      to test these hypotheses, and support the inclusion of criteria relating to
      session length in definitions of adequate HD practice.

PMID- 16609688
TI  - Proinflammatory effects of iron sucrose in chronic kidney disease.
AB  - Inflammation is a central component of progressive chronic kidney disease (CKD).
      Iron promotes oxidative stress and inflammatory response in animals and promotes
      progressive CKD. Parenteral iron provokes oxidative stress in patients with CKD;
      however, its potential to provoke an inflammatory response is unknown. In 20
      veterans with CKD, 100 mg iron sucrose was administered intravenously over 5 min
      and urinary excretion rate and plasma concentration of monocyte chemoattractant
      protein-1 (MCP-1) were measured at timed intervals over 24 h. Patients were then
      randomized to placebo or N-acetyl cysteine (NAC) 600 mg b.i.d. and the experiment
      was repeated at 1 week. Iron sucrose markedly increased plasma concentration and
      urinary excretion rate of MCP-1 at baseline and at 1 week visits (P < 0.0001 for
      time effect). Urinary excretion peaked at 30 min and plasma concentration at 15
      min. Plasma MCP-1 concentration fell from 164 +/- 17.7 to 135 +/- 17.7 pg/ml with
      NAC, whereas it remained unchanged from 133 +/- 12.5 to 132 +/- 17.7 pg/ml with
      placebo (P=0.001 for visit x antioxidant drug interaction). There was a reduction
      in MCP-1 urinary excretion rate from visit 1 to 2. At the baseline visit, the
      urinary excretion rate averaged 305 +/- 66 pg/min and at the second visit 245 +/-
      67 pg/min (mean difference 60 +/- 28 pg/min, P = 0.030). There was no improvement
      in urinary MCP-1 excretion with NAC. In conclusion, iron sucrose causes rapid and
      transient generation and/or release of MCP-1 plasma concentration and increases
      urinary excretion rate, and systemic MCP-1 level but the urinary excretion rate
      is not abrogated with the antioxidant NAC. These results may have implications
      for the progression of CKD with parenteral iron.

PMID- 16609689
TI  - Development of an outpatient finger-prick glomerular filtration rate procedure
      suitable for epidemiological studies.
AB  - Development of an outpatient finger-prick glomerular filtration rate (GFR)
      procedure suitable for epidemiological studies. In clinical practice, reference
      GFR procedures are rarely used; in large-scale research studies, a great deal of
      effort and experience is required to obtain them, which is a considerable
      disincentive to using GFR as an end point. The major problem for both clinical
      staff and the subject is the length of time that the procedure takes, requiring
      continuous attendance in the outpatient clinic or its vicinity. Using iohexol as
      a marker, we therefore propose an alternative approach, which addresses this
      fundamental deterrent to a more widespread use of GFR measurement. Eighty-two GFR
      measurements were performed in a mixture of healthy subjects and patients with
      differing degrees of renal impairment with a wide range of GFRs. Serum was
      obtained from blood samples to enable a reference GFR to be calculated. Blood
      spots were collected on filter paper at the same intervals (120, 180, and 240
      min), allowed to dry, and then sent through the post. Serum and blood spots were
      analyzed simultaneously for each individual by automated reverse-phase high
      pressure liquid chromatography. Standard linear regression analyses confirmed a
      good agreement (r2 = 0.953) between the iohexol serum GFR and iohexol blood spots
      GFR. Bland-Altman analysis confirmed that there was no concentration bias. Paired
      comparisons (Wilcoxon's paired signed rank test) showed no significant difference
      between the two measurements. Capillary sampling is simple, effective, and
      significantly reduces the time and costs of performing plasma clearance GFR
      measurements. This approach will make the GFR measurement more accessible for
      clinical practice and large-scale epidemiological studies may become feasible.

PMID- 16609690
TI  - Elevated initial serum creatinine in Wegener's granulomatosis with anti
      myeloperoxidase autoantibodies.

PMID- 16609691
TI  - Plasma phospholipid transfer protein fused with green fluorescent protein is
      secreted by HepG2 cells and displays phosphatidylcholine transfer activity.
AB  - Phospholipid transfer protein (PLTP) is a serum glycoprotein with a central role
      in high-density lipoprotein metabolism. We created a fusion protein in which
      enhanced green fluorescent protein (EGFP) was fused to the carboxyl-terminus of
      PLTP. Stably transfected HepG2 cells, which overexpress this fusion protein, were
      generated. PLTP-EGFP was translocated into the ER and fluoresced within the
      biosynthetic pathway, showing a marked concentration in the Golgi complex. The
      transfected cells secreted into the growth medium phospholipid transfer activity
      7-fold higher than that of the mock-transfected controls. The medium of the PLTP
      EGFP - expressing cells displayed EGFP fluorescence, demonstrating that both the
      PLTP and the EGFP moieties had attained a biologically active conformation.
      However, the specific activity of PLTP-EGFP in the medium was markedly reduced as
      compared with that of endogenous PLTP. This suggests that the EGFP attached to
      the carboxyl-terminal tail of PLTP interferes with the interaction of PLTP with
      its substrates or with the lipid transfer process itself. Fluorescently tagged
      PLTP is a useful tool for elucidating the intracellular functions of PLTP and the
      interaction of exogenously added PLTP with cells, and will provide a means of
      monitoring the distribution of exogenously added PLTP between serum lipoprotein
      subspecies.

PMID- 16609692
TI  - Molten globule state of human placental cystatin (HPC) at low pH conditions and
      the effects of trifluoroethanol (TFE) and methanol.
AB  - Acid-induced conformational changes were studied in human placental cystatin
      (HPC) in terms of circular dichroism (CD) spectroscopy, the binding of
      hydrophobic dye 1-anilinonapthalene-8-sulphonic acid (ANS), and intrinsic
      fluorescence measurements. Our results show the formation of an acid-induced
      molten globule state at pH 2.0, with significant secondary and tertiary
      interactions that resemble the native state, exposed hydrophobic regions and the
      effects of trifluoroethanol (TFE) and methanol in conversion of the acid
      denatured state of HPC to the alcohol-induced state, which is characterized by
      increased helical content, disrupted tertiary structure, and the absence of
      hydrophobic clusters. Alcohol-induced formation of alpha-helical structures at pH
      2.0 is evident from the increase in the ellipticity values at 222 nm, with native
      like secondary structural features at 40% TFE. The increase in helical content
      was observed up to 80% TFE concentration. The ability of TFE (40%) to refold acid
      denatured HPC to native-state conformation is also supported by intrinsic and ANS
      fluorescence measurements.

PMID- 16609693
TI  - Expression of MG7-Ag in patients with gastric cancer correlates with weaker T
      cell immune response and more proinflammatory cytokine secretion.
AB  - MG7-Ag is a human gastric-carcinoma-associated antigen with a high specificity.
      So far it is remained unclear whether MG7-Ag is correlated with the in vivo
      cellular immune response of patients with gastric cancer. In this study, we
      detected the expression of the T cell receptor (TCR) repertoire of T cell
      subpopulations and cytokines in tumor-infiltrating lymphocytes (TIL), peripheral
      blood lymphocytes (PBL), and residue benign mucosal lymphocytes (NML) of patients
      with gastric cancer using semiquantitative RT-PCR. Our data showed that the
      expanded clones in CD8(+) NML and TIL and CD4+ NML and PBL in MG7-Ag-positive
      patients were significantly fewer than those of MG7-Ag-negative patients (p =
      0.0360; p = 0.0026; p = 0.0065 p = 0.0109, respectively). The levels of IL-8 in
      CD8(+) TIL and TNF in CD4(+) TIL from the MG7-Ag-positive group were
      significantly higher than those from the MG7-Ag-negative group (p = 0.0302; p =
      0.0177, respectively). Taken together, the results demonstrated a weaker T cell
      immune response and more proinflammatory cytokine secretion in MG7-Ag-positive
      patients with gastric cancer than in MG7-Ag-negative ones. This likely
      contributes to the poor prognosis in MG7-Ag-positive gastric-cancer patients.

PMID- 16609694
TI  - Sodium barbital is a slow reversible inactivator of rabbit-muscle creatine
      kinase.
AB  - As a depressant of the central nervous system, the clinical effect of sodium
      barbital has been extensively studied. Here we report on sodium barbital as an
      inhibitor of rabbit-muscle creatine kinase (CK), which plays a significant role
      in energy homeostasis in the muscles. Although sodium barbital gradually inhibits
      the activity of CK with increased concentration, the inhibition effect can be
      completely reversed by dilution, indicating that the inactivation process is
      reversible. Detailed kinetics analysis, according to a previously presented
      theory, indicates that sodium barbital functions as a non complexing inhibitor,
      and its inhibition effect on CK is a slow reversible inactivation. In this study,
      a kinetic model of the substrate reaction is presented, and the microscopic rate
      constants for the reaction of sodium barbital with the free enzyme and the enzyme
      substrate complexes are determined. Kinetic analysis reveals that sodium barbital
      might compete with both creatine and ATP, but mainly with creatine, to inhibit
      the activity of CK. The results suggest that CK might be a target for sodium
      barbital in vivo.

PMID- 16609695
TI  - Secretion of human glucocerebrosidase from stable transformed insect cells using
      native signal sequences.
AB  - The lysosomal hydrolase, glucocerebrosidase (GBA), catalyses the penultimate step
      in the breakdown of membrane glycosphingolipids. An inherited deficiency of this
      enzyme activity leads to the onset of Gaucher disease, the most common lysosomal
      storage disorder. Affected individuals range from adults with hepatosplenomegaly,
      haematological complications, and bone pain (type 1 disease) to children and
      neonates with severe neuronopathy leading to neurological degradation and
      premature death (type 2 and type 3 disease). Enzyme replacement therapy has
      become the standard of treatment for type I Gaucher disease but remains an
      expensive option, in part because of the cost of recombinant enzyme production
      using mammalian cell culture. Using a nonlytic integrative plasmid expression
      system, we have successfully produced active human GBA in stable transformed Sf9
      (Spodoptera frugiperda) cells. Both the 39 and 19 amino acid native GBA signal
      sequences were capable of endoplasmic reticulum targeting, which led to secretion
      of the recombinant protein, although approximately 30% more enzyme was produced
      using the longer signal sequence. The secreted product was purified to apparent
      electrophoretic homogeneity using hydrophobic interaction chromatography and
      found to be produced in a fully glycosylated and a hypoglycosylated form, both of
      which cross-reacted with a human GBA-specific monoclonal antibody. The pH optimum
      (at pH 5.5) for activity of the recombinant enzyme was as expected for human GBA
      using the artificial substrate 4-methyl-umbelliferyl-beta-D-glycopyranoside. With
      initial nonoptimized expression levels estimated at 10-15 mg/L using small-scale
      batch cultures, stable transformed insect cells could provide a viable
      alternative system for the heterologous production of human GBA when grown under
      optimized perfusion culture conditions.

PMID- 16609696
TI  - Contribution of polyunsaturated fatty acids to Shiga toxin cytotoxicity in human
      renal tubular epithelium-derived cells.
AB  - Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli is a critical
      factor in the onset of hemolytic uremic syndrome. The current study was designed
      to assess whether n-3 and (or) n-6 polyunsaturated fatty acids (PUFA) act as a
      valuable adjunct to prevent the cell injury of renal tubule cells in the
      emergence of HUS. The target cells, ACHN cells derived from human tubule
      epithelium, were cultured with each PUFA, then exposed to Stx-1 or Stx-2. The
      rank order of potency of PUFA to inhibit the cell death caused by each toxin was
      as follows: EPA > AA = DHA >> LNA. There were dose-response relations in the
      efficacy of each PUFA. No prophylactic effect was found in the cultures with LA.
      Immunofluorescence assays revealed that both the expression of the toxin receptor
      on ACHN cells and binding between the toxin and cells were unaffected by the
      PUFA. These results suggest that EPA is the most efficacious PUFA against the
      renal tubule cell injury caused by Stx, which may be assigned to an alteration in
      the intracellular pathway leading to cell death.

PMID- 16609697
TI  - Cloning and developmental characterization of Xenopus laevis membrane type-3
      matrix metalloproteinase (MT3-MMP).
AB  - Proper extracellular matrix (ECM) remodeling, mediated by matrix
      metalloproteinases (MMPs), is crucial for the development and survival of
      multicellular organisms. Full-length Xenopus laevis membrane type-3 matrix
      metallo proteinase (MT3-MMP) was amplified by PCR and cloned from a stage 28
      Xenopus head cDNA library. A comparison of the derived Xenopus MT3-MMP protein
      sequence to that of other vertebrates revealed 86% identity with human and mouse
      and 85% identity with chicken. The expression profile of MT3-MMP was examined
      during Xenopus embryogenesis: MT3-MMP transcripts were first detected at the
      later stages of development and were localized to dorsal and anterior structures.
      During metamorphosis and in the adult frog, MT3-MMP expression was restricted to
      specific tissues and organs. Treatment of Xenopus embryos with lithium chloride
      (LiCl), ultraviolet irradiation (UV), or retinoic acid (RA) revealed that MT3-MMP
      levels increased with LiCl-dorsalizing treatments and decreased with UV
      ventralizing and RA-anterior neural truncating treatments. Overexpression of MT3
      MMP through RNA injections led to dose-dependent developmental abnormalities and
      death. Moreover, MT3-MMP overexpression resulted in neural and head structure
      abnormalities, as well as truncated axes. Taken together, these results indicate
      that MT3-MMP expression in Xenopus is spatially and temporally restricted.
      Furthermore, deregulation of MT3-MMP during early embryogenesis has detrimental
      effects on development.

PMID- 16609698
TI  - A novel ribonuclease from fresh fruiting bodies of the portabella mushroom
      Agaricus bisporus.
AB  - A 14 kDa ribonuclease with a novel N-terminal sequence was isolated from fresh
      fruiting bodies of the portabella mushroom. It was adsorbed on DEAE-cellulose and
      carboxymethyl-cellulose, and demonstrated the highest ribonucleolytic potency
      toward poly (A), 60% as much activity toward poly (C), 40% as much activity
      toward poly (U), and the least activity (7% as much) toward poly (G). It
      exhibited a pH optimum at pH 4.5 and a temperature optimum at 60 degrees C. Its
      activity at 100 degrees C was higher than that at 20 degrees C.

PMID- 16609699
TI  - The structural basis for the serospecificity of Actinobacillus suis serogroup
      O:2.
AB  - Actinobacillus suis is an important bacterial pathogen of healthly pigs. An O
      antigen (lipopolysaccharide; LPS) serotyping system is being developed to study
      the prevalence and distribution of representative isolates from both healthy and
      diseased pigs. In a previous study, we reported that A. suis serogroup O:1
      strains express LPS with a (1-->6)-beta-D-glucan O-antigen chain polysaccharide
      that is similar in structure to a key cell-wall component in yeasts, such as
      Saccharomyces cerevisiae and Candida albicans. This study describes the O-antigen
      polysaccharide chemical structure of an O:2 serogroup strain, A. suis H91-0380,
      which possesses a tetrasaccharide repeating block with the structure: -->3)-beta
      D-Galp-(1-->4)-[alpha-D-Galp-(1-->6)]-beta-D-Glcp-(1-->6)-beta-D-GlcpNAc-(1-->.
      Studies have shown that A. suis serogroup O:2 strains are associated with
      severely diseased animals; therefore, work on the synthesis of a glycoconjugate
      vaccine employing O:2 O-antigen polysaccharide to vaccinate pigs against A. suis
      serogroup O:2 strains is currently underway.

PMID- 16609700
TI  - Control of mitochondrial gene expression in the aging rat myocardium.
AB  - Aging induces complex changes in myocardium bioenergetic and contractile
      properties. Using F344BNF(1) rats, we examined age-dependent changes in
      myocardial bioenergetic enzymes (catalytic activities and transcript levels) and
      mRNA levels of putative transcriptional regulators of bioenergetic genes. Very
      old rats (35 months) showed a 22% increase in ventricular mass with no changes in
      DNA or RNA per gram. Age-dependent cardiac hypertrophy was accompanied by complex
      changes in mitochondrial enzymes. Enzymes of the Krebs cycle and electron
      transport system remained within 15% of the values measured in adult heart,
      significant decreases occurring in citrate synthase (10%) and aconitase (15%).
      Transcripts for these enzymes were largely unaffected by aging, although mRNA
      levels of putative transcriptional regulators of the enzymes (nuclear respiratory
      factor (NRF) 1 and 2 alpha subunit) increased by about 30%-50%. In contrast,
      enzymes of fatty acid oxidation exhibited a more diverse pattern, with a 50%
      decrease in beta-hydroxyacyl-CoA dehydrogenase (HOAD) and no change in long-chain
      acyl-CoA dehydrogenase or carnitine palmitoyltransferase. Transcript levels for
      fatty acid oxidizing enzymes covaried with HOAD, which declined significantly by
      30%. There were no significant changes in the relative transcript levels of
      regulators of genes for fatty acid oxidizing enzymes: peroxisome proliferator
      activated receptor-alpha (PPARalpha), PPARbeta, or PPARgamma coactivator-1alpha
      (PGC-1alpha). There were no changes in the mRNA levels of Sirt1, a histone
      modifying enzyme that interacts with PGC-1alpha. Collectively, these data suggest
      that aging causes complex changes in the enzymes of myocardial energy metabolism,
      triggered in part by NRF-independent pathways as well as post-transcriptional
      regulation.

PMID- 16609701
TI  - ZNRD1 mediates resistance of gastric cancer cells to methotrexate by regulation
      of IMPDH2 and Bcl-2.
AB  - We previously showed that downregulation of a transcription-associated gene
      (ZNRD1) could reverse the resistant phenotype of gastric cancer cells through
      regulation of the transcription of multidrug resistance gene 1 (MDR1). In the
      present study, we determined both known and novel differentially expressed genes
      in VCR-induced multidrug resistant gastric cancer cell SGC7901/VCR transfected
      with ZNRD1 siRNA or empty vector control. Screening was performed using the Human
      Cancer Xpro(tm) HC-III plus arrays, containing 3072 cancer-related cDNAs. Ten
      genes, involved in cell cycle control, nucleic acid binding, and protein
      phosphorylation, among other functions, underwent more than 5-fold change. Of the
      downregulated genes we chose Inosine monophosphate dehydrogenase 2 (IMPDH2) for
      further validation by quantitative RT-PCR. In vitro and in vivo drug sensitivity
      analyses revealed that inhibition of ZNRD1 and IMPDH2 activity sensitized
      SGC7901/VCR cells to methotrexate. Additionally, inhibition of ZNRD1 could
      suppress adriamycin-induced apoptosis and significantly downregulate the
      expression of Bcl-2, but it did not alter the expression of the glutathione-S
      transferase, or intracellular glutathione content. Taken together, the findings
      suggest that ZNRD1 could act as a modulator of methotrexate chemotherapy in
      gastric cancer cells through the regulation of IMPDH2 and Bcl-2.

PMID- 16609702
TI  - Leptin biosynthetic pathway in white adipocytes.
AB  - The aim of this study was to determine through morphological and biochemical
      means the biosynthetic and secretory pathway followed by leptin in adipocytes.
      Immunocytochemistry revealed the presence of leptin in the rough endoplasmic
      reticulum, the Golgi apparatus, and in numerous small vesicles along the plasma
      membrane of white adipo cytes. In vitro, isolated adipocytes under nonstimulated
      conditions (basal) continuously secreted leptin while their intra cellular
      content remained unchanged. When adipocytes were stimulated with insulin, leptin
      cellular content and secretion increased in parallel and were significantly
      different from basal secretion only after 45 min. L-leucine and L-glutamate also
      strongly stimulated leptin synthesis and secretion. These stimulating effects
      were abolished by cycloheximide and brefeldin A. The transcriptional inhibitor
      actinomycin D did not have any effects in either basal or stimulated conditions.
      Leptin mRNA levels were not affected by any stimulating or inhibiting agents.
      Finally, norepinephrine, isoproterenol, CL316243, and palmitate inhibited the
      effects of insulin, L-leucine, and L-glutamate on leptin synthesis. We thus
      conclude that (i) adipocytes continuously synthesize and secrete leptin along a
      rough endoplasmic reticulum-Golgi secretory vesicles pathway, (ii) an increase in
      leptin secretion requires increased de novo synthesis, and (iii) short-term
      leptin secretion does not involve changes in mRNA levels.

PMID- 16609703
TI  - Cellular concentrations of glutamine synthetase in murine organs.
AB  - Glutamine synthetase (GS) is the only enzyme that can synthesize glutamine, but
      it also functions to detoxify glutamate and ammonia. Organs with high cellular
      concentrations of GS appear to function primarily to remove glutamate or ammonia,
      whereas those with a low cellular concentration appear to primarily produce
      glutamine. To validate this apparent dichotomy and to clarify its regulation, we
      determined the GS concentrations in 18 organs of the mouse. There was a >100-fold
      difference in GS mRNA, protein, and enzyme-activity levels among organs, whereas
      there was only a 20-fold difference in the GS protein:mRNA ratio, suggesting
      extensive transcriptional and posttranscriptional regulation. In contrast, only
      small differences in the GS enzyme activity : protein ratio were found,
      indicating that posttranslational regulation is of minor importance. The cellular
      concentration of GS was determined by relating the relative differences in
      cellular GS concentration, detected using image analysis of immunohistochemically
      stained tissue sections, to the biochemical data. There was a >1000-fold
      difference in cellular concentrations of GS between GS-positive cells in
      different organs, and cellular concentrations were up to 20x higher in
      subpopulations of cells within organs than in whole organs. GS activity was
      highest in pericentral hepatocytes (approximately 485 micromol.g(-1).min-(1),
      followed in descending order by epithelial cells in the epididymal head, Leydig
      cells in the testicular interstitium, epithelial cells of the uterine tube, acid
      producing parietal cells in the stomach, epithelial cells of the S3 segment of
      the proximal convoluted tubule of the kidney, astrocytes of the central nervous
      tissue, and adipose tissue. GS activity in muscle amounted to only 0.4
      micromol.g(-1).min(-1). Our findings confirmed the postulated dichotomy between
      cellular concentration and GS function.

PMID- 16609704
TI  - Harnessing asymmetrical substrate recognition by thermostable EndoV to achieve
      balanced linear amplification in multiplexed SNP typing.
AB  - Multiplexed amplification of specific DNA sequences, by PCR or by strand
      displacement amplification, is an intrinsically biased process. The relative
      abundance of amplified DNA can be altered significantly from the original
      representation and, in extreme cases, allele dropout can occur. In this paper, we
      present a method of linear amplification of DNA that relies on the cooperative,
      sequence-dependent functioning of the DNA mismatch-repair enzyme endonuclease V
      (EndoV) from Thermotoga maritima (Tma) and Bacillus stearothermophilus (Bst) DNA
      polymerase. Tma EndoV can nick one strand of unmodified duplex DNA, allowing
      extension by Bst polymerase. By controlling the bases surrounding a mismatch and
      the mismatch itself, the efficiency of nicking by EndoV and extension by Bst
      polymerase can be controlled. The method currently allows 100-fold multiplexed
      amplification of target molecules to be performed isothermally, with an average
      change of <1.3-fold in their original representation. Because only a single
      primer is necessary, primer artefacts and nonspecific amplification products are
      minimized.

PMID- 16609705
TI  - Cellular localization of 17 natural mutant variants of ALADIN protein in triple A
      syndrome - shedding light on an unexpected splice mutation.
AB  - The triple A syndrome is a complex and multisystemic autosomal recessive disease
      with the 3 main symptoms of adrenal insufficiency, alacrima, and achalasia
      accompanied by neurological impairment. Mutations in the AAAS gene on chromosome
      12q13 are responsible for the disorder. AAAS encodes a protein named ALADIN,
      which belongs to the family of WD-repeat-containing proteins and has been shown
      to localize to nuclear pore complexes. The function of the protein is not clear.
      It is supposed that ALADIN plays an important role in RNA and (or) protein
      trafficking between the nucleus and cytoplasm. With transfection experiments, we
      analyzed the cellular localization of the wild-type and 17 natural mutant
      variants (9 missense, 5 nonsense, 3 frameshift mutations) of ALADIN. We show that
      most mutations cause mislocalization of the mutant ALADIN proteins in the
      cytoplasm. In contrast, some variants with mutations located at the N-terminus
      (Q15K, L25P) and 3 artificial C-terminus mutations (Q490X, R493X, and V497X)
      remain at the nuclear pore. Using a patient cell line, we show that the mutation
      43C>A in exon 1 does not cause a missense mutation Q15K but, rather, results in
      aberrant splicing.

PMID- 16609706
TI  - Differential abilities of mouse liver parenchymal and nonparenchymal cells in HDL
      and LDL (native and oxidized) association and cholesterol efflux.
AB  - The aim of this study was to quantify the abilities of mouse liver parenchymal
      and nonparenchymal cells with respect to (i) cholesteryl ester (CE) selective
      uptake from low-density lipoproteins (LDL), oxidized LDL (OxLDL), and high
      density lipoprotein (HDL); and (ii) their free cholesterol efflux to HDL. The
      preparations of cells were incubated with lipoproteins labelled either in protein
      with iodine-125 or in CE with 3H-cholesterol oleate, and lipoprotein-protein and
      lipoprotein-CE associations were measured. The associations of LDL-protein and
      LDL-CE with nonparenchymal cells were 5- and 2-fold greater, respectively, than
      with parenchymal cells. However, in terms of CE-selective uptake (CE association
      minus protein association) both types of cell were equivalent. Similar results
      were obtained with OxLDL, but both types of cell showed higher abilities in OxLDL
      CE than in LDL-CE selective uptake (on average by 3.4-fold). The association of
      HDL-protein with nonparenchymal cells was 3x that with parenchymal cells;
      however, nonparenchymal cells associated 45% less HDL-CE. Contrary to parenchymal
      cells, nonparenchymal cells did not show HDL-CE selective uptake activity. Thus
      parenchymal cells selectively take CE from the 3 types of lipoproteins, whereas
      nonparenchymal cells exert this function only on LDL and OxLDL. Efflux was 3.5
      fold more important in nonparenchymal than in parenchymal cells.

PMID- 16609707
TI  - Conservation of Pitx1 expression during amphibian limb morphogenesis.
AB  - In contrast to the pattern of limb emergence in mammals, chicks, and the newt N.
      viridescens, embryos such as Xenopus laevis and Eleutherodactylus coqui initiate
      pelvic limb buds before they develop pectoral ones. We studied the expression of
      Pitx1 in X. laevis and E. coqui to determine if this paired-like homeodomain
      transcription factor directs differentiation specifically of the hindlimb, or if
      it directs the second pair of limbs to form, namely the forelimbs. We also
      undertook to determine if embryonic expression patterns were recapitulated during
      the regeneration of an amputated limb bud. Pitx1 is expressed in hindlimbs in
      both X. laevis and E. coqui, and expression is similar in both developing and
      regenerating limb buds. Expression in hindlimbs is restricted to regions of
      proliferating mesenchyme.

PMID- 16609708
TI  - Papers from the 4th Conference on Ethics and Social Responsibility in Engineering
      and Technology, June 9-10, 2005, Los Angeles, California, USA.

PMID- 16609709
TI  - Teaching ethics in engineering education through historical analysis.
AB  - The goal of this paper is to stress the significance of ethics for engineering
      education and to illustrate how it can be brought into the mainstream of higher
      education in a natural way that is integrated with the teaching objectives of
      enriching the core meaning of engineering. Everyone will agree that the
      practicing engineer should be virtuous, should be a good colleague, and should
      use professional understanding for the common good. But these injunctions to
      virtue do not reach closely enough the ethic of the engineer as engineer, as
      someone acting in a uniquely engineering situation, and it is to such conditions
      that I wish to speak through a set of specific examples from recent history. I
      shall briefly refer to four controversies between engineers. Then, in some detail
      I shall narrate three historical cases that directly involve the actions of one
      engineer, and finally I would like to address some common contemporary issues.
      The first section, Engineering Ethics and the History of Innovation, includes
      four cases involving professional controversy. Each controversy sets two people
      against each other in disputes over who invented the telegraph, the radio, the
      automobile, and the airplane. In each dispute, it is possible to identify ethical
      and unethical behavior or ambiguous ethical behavior that serves as a basis for
      educational discussion. The first two historical cases described in "Crises and
      the Engineer" involve the primary closure dam systems in The Netherlands, each
      one the result of the actions of one engineer. The third tells of an American
      engineer who took his political boss, a big city mayor, to court over the illegal
      use of a watershed. The challenges these engineers faced required, in the deepest
      sense, a commitment to ethical behavior that is unique to engineering and
      instructive to our students. Finally, the cases in "Professors and Comparative
      Critical Analysis" illuminate the behavior of engineers in the design of
      structures and also how professors can make public criticisms of designs that
      seem wasteful.

PMID- 16609710
TI  - Engineering ethics, individuals, and organizations.
AB  - This article evaluates a family of criticism of how engineering ethics is now
      generally taught. The short version of the criticism might be put this way:
      Teachers of engineering ethics devote too much time to individual decisions and
      not enough time to social context. There are at least six version of this
      criticism, each corresponding to a specific subject omitted. Teachers of
      engineering ethics do not (it is said) teach enough about: 1) the culture of
      organizations; 2) the organization of organizations; 3) the legal environment of
      organizations; 4) the role of professions in organizations; 5) the role of
      organizations in professions; or 6) the political environment of organizations.
      My conclusion is that, while all six are worthy subjects, there is neither much
      reason to believe that any of them are now absent from courses in engineering
      ethics nor an obvious way to decide whether they (individually or in combination)
      are (or are not) now being given their due. What we have here is a dispute about
      how much is enough. Such disputes are not to be settled without agreement
      concerning how we are to tell we have enough of this or that. Right now we seem
      to lack that agreement and not to have much reason to expect it any time soon.

PMID- 16609711
TI  - The complex challenges of ethical choices by engineers in public service.
AB  - This paper proposes that engineers in public service are confronted with
      unavoidable complexity in their ethical considerations. The complexity begins
      with interactions among venues of ethical choices. Engineers must make ethical
      choices simultaneously at the individual, professional, organizational and
      societal levels. These ethical domains often conflict. The complexity also stems
      from situations in which physical properties may remain stable, but important
      social, economic, institutional and political conditions can change
      substantially. The paper proposes that the reflective learning approach of
      pragmatism can help with these challenging situations. This approach depends upon
      employing Dewey's five stage process of inquiry to engage the ethical complexity
      inherent in the practice of engineering in the public service.

PMID- 16609712
TI  - Developing an ethical code for engineers: the discursive approach.
AB  - From the Hippocratic Oath on, deontological codes and other professional self
      regulation mechanisms have been used to legitimize and identify professional
      groups. New technological challenges and, above all, changes in the socioeconomic
      environment require adaptable codes which can respond to new demands. We assume
      that ethical codes for professionals should not simply focus on regulative
      functions, but must also consider ideological and educative functions. Any
      adaptations should take into account both contents (values, norms and
      recommendations) and the drafting process itself. In this article we propose a
      process for developing a professional ethical code for an official professional
      association (Colegio Oficial de Ingenieros Industriales de Valencia (COIIV)
      starting from the philosophical assumptions of discursive ethics but adapting
      them to critical hermeneutics. Our proposal is based on the Integrity Approach
      rather than the Compliance Approach. A process aiming to achieve an effective
      ethical document that fulfils regulative and ideological functions requires a
      participative, dialogical and reflexive methodology. This process must respond to
      moral exigencies and demands for efficiency and professional effectiveness. In
      addition to the methodological proposal we present our experience of producing an
      ethical code for the industrial engineers' association in Valencia (Spain) where
      this methodology was applied, and we evaluate the detected problems and future
      potential.

PMID- 16609713
TI  - On complicity theory.
AB  - The received account of whistleblowing, developed over the last quarter century,
      is identified with the work of Norman Bowie and Richard DeGeorge. Michael Davis
      has detailed three anomalies for the received view: the paradoxes of burden,
      missing harm and failure. In addition, he has proposed an alternative account of
      whistleblowing, viz., the Complicity Theory. This paper examines the Complicity
      Theory. The supposed anomalies rest on misunderstandings of the received view or
      misreadings of model cases of whistleblowing, for example, the Challenger
      disaster and the Ford Pinto. Nevertheless, the Complicity Theory is important for
      as in science the contrast with alternative competing accounts often helps us
      better understand the received view. Several aspects of the received view are
      reviewed and strengthened through comparison with Complicity Theory, including
      why whistleblowing needs moral justification. Complicity Theory is also
      critiqued. The fundamental failure of Complicity Theory is its failure to explain
      why government and the public encourage and protect whistleblowers despite the
      possibility of considerable harm to the relevant company in reputation, lost
      jobs, and lost shareholder value.

PMID- 16609714
TI  - Ethical considerations and proposed guidelines for the use of radio frequency
      identification: especially concerning its use for promoting public safety and
      national security.
AB  - Radio Frequency Identification (RFID) is quickly growing in its applications. A
      variety of uses for the technology are beginning to be developed, including chips
      which can be used in identification cards, in individual items, and for human
      applications, allowing a chip to be embedded under the skin. Such chips could
      provide numerous benefits ranging from day-to-day convenience to the increased
      ability of the federal government to adequately ensure the safety of its
      citizens. However, there are also valid concerns about the potential of this
      technology to infringe on privacy, creating fears of a surveillance society.
      These are concerns that must be addressed quickly, with sensitivity to individual
      interests and societal welfare, allowing humanity to reap the benefits of
      convenience and safety without paying an unacceptable price in the loss of
      privacy.

PMID- 16609715
TI  - PRiME: integrating professional responsibility into the engineering curriculum.
AB  - Engineering educators have long discussed the need to teach professional
      responsibility and the social context of engineering without adding to
      overcrowded curricula. One difficulty we face is the lack of appropriate teaching
      materials that can fit into existing courses. The PRiME (Professional
      Responsibility Modules for Engineering) Project
      (http://www.engr.utexas.edu/ethics/primeModules.cfm) described in this paper was
      initiated at the University of Texas, Austin to provide web-based modules that
      could be integrated into any undergraduate engineering class. Using HPL (How
      People Learn) theory, PRiME developed and piloted four modules during the
      academic year 2004-2005. This article introduces the modules and the pilot,
      outlines the assessment process, analyzes the results, and describes how the
      modules are being revised in light of the initial assessment. In its first year
      of development and testing, PRiME made significant progress towards meeting its
      objectives. The PRiME Project can strengthen engineering education by providing
      faculty with an effective system for engaging students in learning about
      professional responsibility.

PMID- 16609716
TI  - A single instrument: engineering and engineering technology students
      demonstrating competence in ethics and professional standards.
AB  - This paper details efforts by the Purdue School of Engineering and Technology at
      Indiana University Purdue University Indianapolis (IUPUI) to create a single
      instrument for honors science, technology, engineering and mathematics (STEM)
      students wishing to demonstrate competence in the IUPUI Principles of
      Undergraduate Learning (PUL's) and Accreditation Board for Engineering and
      Technology (ABET) Engineering Accreditation Criterion (EAC) and Technology
      Accreditation Criterion (TAC) 2, a through k. Honors courses in Human Behavior,
      Ethical Decision-Making, Applied Leadership, International Issues and Leadership
      Theories and Processes were created along with a specific menu of activities and
      an assessment rubric based on PUL's and ABET criteria to evaluate student
      performance in the aforementioned courses. Students who complete the series of 18
      Honors Credit hours are eligible for an Honors Certificate in Leadership Studies
      from the Department of Organizational Leadership and Supervision. Finally, an
      accounting of how various university assessment criteria, in this case the IUPUI
      Principles of Undergraduate Learning, can be linked to ABET outcomes and prove
      student competence in both, using the aforementioned courses, menu of items, and
      assessment rubrics; these will be analyzed and discussed.

PMID- 16609717
TI  - A team-taught interdisciplinary approach to engineering ethics.
AB  - This paper outlines the development and implementation of a new course in
      Engineering Ethics at the University of Tennessee. This is a three-semester-hour
      course and is jointly taught by an engineering professor and a philosophy
      professor. While traditional pedagogical techniques such as case studies,
      position papers, and classroom discussions are used, additional activities such
      as developing a code of ethics and student-developed scenarios are employed to
      encourage critical thinking. Among the topics addressed in the course are
      engineering as a profession and its role in society; ethical successes and
      failures; risk, safety, and the environment; professional responsibilities;
      credit and intellectual property; and international concerns. The most
      significant aspect of the course is that it brings both engineering and non
      engineering points of view to the topics at hand. This is accomplished in two
      ways. First, as mentioned previously, it is team-taught by engineering faculty
      with an interest in ethical and societal issues, and by philosophy faculty with
      expertise in the field of professional ethics and an interest in science and
      technology. Second, the course is offered to both engineers and non-engineers.
      This mix of students requires that all students must be able to explain their
      technical and ethical decisions in a non-technical manner. Work teams are
      structured to maximize interdisciplinary interaction and to foster insights by
      each student into the professional commitments and attitudes of others.

PMID- 16609718
TI  - Teaching engineering ethics using role-playing in a culturally diverse student
      group.
AB  - The use of role-playing ("active learning") as a teaching tool has been reported
      in areas as diverse as social psychology, history and analytical chemistry. Its
      use as a tool in the teaching of engineering ethics and professionalism is also
      not new, but the approach develops new perspectives when used in a college class
      of exceptionally wide cultural diversity. York University is a large urban
      university (40,000 undergraduates) that draws its enrolment primarily from the
      Greater Toronto Area, arguably one of the most culturally diverse cities in the
      world, embracing the largest percentage of Canada's immigration. Among the area's
      five million inhabitants, 50% identify themselves as a visible minority born
      outside Canada, while over 100 languages and dialects are spoken daily. Although
      students admitted from this international pool have usually been exposed to
      western attitudes during secondary education and are rapidly assimilated into
      Canadian culture, responses to specific ethical issues are strongly influenced by
      their prior culture. Two and three-part scripts for case studies based on NSF or
      original scenarios were written to illustrate issues such as gifts, attitudes
      towards women and ethnic minorities, conflict of interest, whistle-blowing,
      sexual harassment, individual rights, privacy, environment, intellectual
      property, and others. Following the presentation, the actors lead group
      discussion based on previously specified questions. Once the initial shyness and
      reluctance of some cultures has been overcome through the building of rapport,
      students have written original scripts based on hypothetical or prior personal
      situations. The method is now being adopted in a short course format to assist
      the professional integration of foreign trained engineers.

PMID- 16609719
TI  - The use of moral dilemmas for teaching agricultural engineers.
AB  - Agricultural engineers' jobs are especially related to sustainability and earth
      life issues. They usually work with plants or animals, and the aim of their work
      is often linked to producing food to allow people to improve their quality of
      life. Taking into account this dual function, the moral requirements of their day
      to-day professional practice are arguably greater than those of other
      professions. Agricultural engineers can develop their ability to live up to this
      professional responsibility by receiving ethical training during their university
      studies, not only by taking courses specifically devoted to ethics, but also by
      having to deal with moral questions that are integrated into their technical
      courses through a program of Ethics Across the Curriculum (EAC). The authors feel
      that a suitable pedagogical technique for achieving this goal is the use of moral
      dilemmas, following Kohlberg's theory of levels of morality (1981), with the
      final objective of attaining a post-conventional level. This paper examines the
      possibilities and limitations of using moral dilemmas as a pedagogical technique
      for training agricultural engineers. The cases, discussions, and evaluation used
      in the Agricultural Engineering Department of the Technical University of
      Valencia (Spain) are also presented.

PMID- 16609720
TI  - On teaching computer ethics within a computer science department.
AB  - The author has surveyed a quarter of the accredited undergraduate computer
      science programs in the United States. More than half of these programs offer a
      'social and ethical implications of computing' course taught by a computer
      science faculty member, and there appears to be a trend toward teaching ethics
      classes within computer science departments. Although the decision to create an
      'in house' computer ethics course may sometimes be a pragmatic response to
      pressure from the accreditation agency, this paper argues that teaching ethics
      within a computer science department can provide students and faculty members
      with numerous benefits. The paper lists topics that can be covered in a computer
      ethics course and offers some practical suggestions for making the course
      successful.

PMID- 16609721
TI  - Ethical considerations of the short-term and long-term health impacts, costs, and
      educational value of sustainable development projects.
AB  - There are over 800 seventh to tenth grade students at the College d'Enseignment
      Generale (CEG) School in Azove, Benin. Like most children in the developing
      world, these students lack access to clean water and basic sanitation facilities.
      These students suffer from parasitic infection and health ailments which could be
      directly offset with short term aid to supply water and medical aid. Promoting
      proper sanitation and providing the technology to implement water and wastewater
      treatment in the community will decrease childhood and maternal disease and
      mortality rates in Azove. However, these measures may take several years to
      implement and will require a significant investment in the infrastructure of the
      school. Is it ethical to spend 10,000 dollars towards the long-term goals of
      providing water and sanitation to the students of CEG Azove, compared to spending
      the same amount on short-term relief efforts? This paper addresses the ethical
      dilemma of dealing with immediate medical needs in developing countries while
      trying to implement sustainable technologies. The views and frustration of
      students working on the project are discussed, as they realize the monetary and
      short-term impacts on human health when implementing sustainable technologies.
      The opportunity costs associated with the education principles of sustainable
      development were also considered. The anticipated costs and health impacts in the
      short-term and long-term will be evaluated for a period of 1, 2, 5 and 10 years.
      Sustainable development requires a new way of thinking, and a long-term approach.
      These problems will require the dedication of a new generation of engineers,
      working hand-in-hand with local communities and governments, social scientists,
      economists, businesses, human rights organizations, other non-government
      organizations, and international development organizations. Design projects
      encourage the professional and ethical development of engineers through hands-on
      involvement in national and international development projects.

PMID- 16609722
TI  - The Small Helm Project: an academic activity addressing international corruption
      for undergraduate civil engineering and construction management students.
AB  - This paper presents an academic project that addresses the issue of international
      corruption in the engineering and construction industry, in a manner that
      effectively incorporates several learning experiences. The major objectives of
      the project are to provide the students a learning activity that will 1) make a
      meaningful contribution within the disciplines being studied; 2) teach by
      experience a significant principle that can be valuable in numerous situations
      during an individual's career, and 3) engage the minds, experiences, and
      enthusiasm of the participants in a real ethical challenge that is prevalent in
      all of their chosen professional fields. The paper describes the full details of
      the project, the actual implementation of it during Winter Semester 2005, the
      experiences gained during the initial trial, and the modifications and
      improvements incorporated for future implementation.

PMID- 16609723
TI  - Engineering the just war: examination of an approach to teaching engineering
      ethics.
AB  - The efficiency of engineering applied to civilian projects sometimes threatens to
      run away with the social agenda, but in military applications, engineering often
      adds a devastating sleekness to the inevitable destruction of life. The relative
      crudeness of terrorism (e.g., 9/11) leaves a stark after-image, which belies the
      comparative insignificance of random (as opposed to orchestrated) belligerence.
      Just as engineering dwarfs the bricolage of vernacular design 'moving us past the
      appreciation of brush-strokes, so to speak' the scale of engineered destruction
      makes it difficult to focus on the charred remains of individual lives. Engineers
      need to guard against the inappropriate military subsumption of their effort.
      Fortunately, the ethics of warfare has been an ongoing topic of discussion for
      millennia. This paper will examine the university core class I've developed (The
      Moral Dimensions of Technology) to meet accreditation requirements in engineering
      ethics, and the discussion with engineering and non-engineering students focused
      by the life of electrical engineer Vannevar Bush, with selected readings in moral
      philosophy from the Dao de Jing, Lao Tze, Cicero, Aurelius Augustinus, Kant,
      Annette Baier, Peter Singer, Elizabeth Anscombe, Philippa Foot, and Judith
      Thomson.

PMID- 16609724
TI  - Global challenges as inspiration: a classroom strategy to foster social
      responsibility.
AB  - Social responsibility is at the heart of the Engineer's Creed embodied in the
      pledge that we will dedicate [our] professional knowledge and skill to the
      advancement and betterment of human welfare... [placing] public welfare above all
      other considerations. However, half century after the original creed was written,
      we find ourselves in a world with great technological advances and great global
      scale technologically-enabled peril. These issues can be naturally integrated
      into the engineering curriculum in a way that enhances the development of the
      technological skill set. We have found that these global challenges create a
      natural opportunity to foster social responsibility within the engineering
      students whom we educate. In freshman through senior-level materials engineering
      courses, we used five guiding principles to shape several different classroom
      activities and assignments. Upon testing an initial cohort of 28 students had
      classroom experiences based on these five principles, we saw a shift in attitude:
      before the experience, 18% of the cohort viewed engineers as playing an active
      role in solving global problems; after the experiences, 79% recognized the
      engineer's role in solving global-scale problems. In this paper, we present how
      global issues can be used to stimulate thinking for socially-responsible
      engineering solutions. We set forth five guiding principles that can foster the
      mindset for socially responsible actions along with examples of how these
      principles translate into classroom activities.

PMID- 16609725
TI  - Teaching ethics: more than an honor code.
AB  - An honor code is certainly a good place to start teaching engineering students
      about ethics, but teaching students to live honorably requires far more effort
      than memorizing a code of ethics statement or applying it just to academic
      performance. In the School of Engineering at Grand Valley State University, we
      have followed the model provided by the United States Military Academy at West
      Point. For our students this involves an introduction to the Honor Code as part
      of a larger Honor Concept at the very beginning of their studies and then making
      it an integral part of their preparation as engineers. The challenge is
      significant because the culture at large does not support living with an Honor
      Concept. This paper will begin with a discussion of the cultural context in which
      we must teach, because that context has changed significantly in the years since
      many faculty members were students themselves. The rest of the paper will detail
      the approach that we have taken to teach ethics as an engineer's way of life.

PMID- 16609726
TI  - Yoga and the battlefield of ethics: highlighting an infusion model for ethics
      education.
AB  - This paper articulates an infusion model of ethics education for engineering
      students by illuminating the value of a religious studies course on yoga. This
      model is distinguished from four other possible approaches that have
      traditionally been used to prepare engineering students to face the challenges of
      the work place. The article is not claiming that this approach should be used to
      the exclusion of the other approaches, but rather that it adds strength to the
      other approaches. Specifically, the article claims that the infusion model
      provides an opportunity for students to reflect upon the foundational ethical
      positions emanating from the world's religions and thereby provides them with a
      vista from which they can not only ask what professional ethical code applies in
      a given situation, but also ponder the nature of character needed to follow that
      ethical code.

PMID- 16609727
TI  - Promoting peace in engineering education: modifying the ABET criteria.
AB  - Modifications to the ABET Criterion 3 are suggested in support of the effort to
      promote the pursuit of peace in engineering education. The proposed modifications
      are the result of integrating the United Nations' sponsored "Integral Model of
      Education for Peace, Democracy and Sustainable Development" into the modern
      engineering curriculum. The key elements of the model are being at peace with
      oneself, being at peace with others, and being at peace with the planet. In
      addition to proposing modifications, specific classroom activities are described
      and implemented, and students' reactions and the effectiveness of the various
      exercises are discussed.

PMID- 16609728
TI  - The integration hypothesis: an evolutionary pathway to benign SIV infection.

PMID- 16609729
TI  - Ancestral genomes, sex, and the population structure of Trypanosoma cruzi.
AB  - Acquisition of detailed knowledge of the structure and evolution of Trypanosoma
      cruzi populations is essential for control of Chagas disease. We profiled 75
      strains of the parasite with five nuclear microsatellite loci, 24Salpha RNA
      genes, and sequence polymorphisms in the mitochondrial cytochrome oxidase subunit
      II gene. We also used sequences available in GenBank for the mitochondrial genes
      cytochrome B and NADH dehydrogenase subunit 1. A multidimensional scaling plot
      (MDS) based in microsatellite data divided the parasites into four clusters
      corresponding to T. cruzi I (MDS-cluster A), T. cruzi II (MDS-cluster C), a third
      group of T. cruzi strains (MDS-cluster B), and hybrid strains (MDS-cluster BH).
      The first two clusters matched respectively mitochondrial clades A and C, while
      the other two belonged to mitochondrial clade B. The 24Salpha rDNA and
      microsatellite profiling data were combined into multilocus genotypes that were
      analyzed by the haplotype reconstruction program PHASE. We identified 141
      haplotypes that were clearly distributed into three haplogroups (X, Y, and Z).
      All strains belonging to T. cruzi I (MDS-cluster A) were Z/Z, the T. cruzi II
      strains (MDS-cluster C) were Y/Y, and those belonging to MDS-cluster B
      (unclassified T. cruzi) had X/X haplogroup genotypes. The strains grouped in the
      MDS-cluster BH were X/Y, confirming their hybrid character. Based on these
      results we propose the following minimal scenario for T. cruzi evolution. In a
      distant past there were at a minimum three ancestral lineages that we may call,
      respectively, T. cruzi I, T. cruzi II, and T. cruzi III. At least two
      hybridization events involving T. cruzi II and T. cruzi III produced
      evolutionarily viable progeny. In both events, the mitochondrial recipient (as
      identified by the mitochondrial clade of the hybrid strains) was T. cruzi II and
      the mitochondrial donor was T. cruzi III.

PMID- 16609732
TI  - Effectiveness of diabetes resource nurse case management and physician profiling
      in a fee-for-service setting: a cluster randomized trial.
AB  - Nurses with advanced training-diabetes resource nurses (DRNs)-can improve care
      for people with diabetes in capitated payment settings. Their effectiveness in
      fee-for-service settings has not been investigated. We conducted a 12-month
      practice-randomized trial involving 22 practices in a fee-for-service
      metropolitan network with 92 primary care physicians caring for 1891 Medicare
      patients >=65 years with diabetes mellitus. Each practice was randomized to one
      of three intervention groups: physician feedback on process measures using
      Medicare claims data; Medicare claims feedback plus feedback on clinical measures
      from medical record (MR) abstraction; or both types of feedback plus a practice
      based DRN. The primary endpoint investigated was hemoglobin A(1c) level. Other
      measures were low-density lipoprotein (LDL) cholesterol level, blood pressure,
      annual hemoglobin A(1c) testing, annual LDL screening, annual eye exam, annual
      foot exam, and annual renal assessment. Data were collected from medical chart
      abstraction and Medicare claims. The number of patients with hemoglobin A(1c) <9%
      increased by 4 (0.9%) in the Claims group; 9 (2.1%) in the Claims + MR group
      (comparison with Claims: P = 0.97); and 16 (3.8%) in the DRN group (comparison
      with Claims: P = 0.31). Results were similar for the other clinical outcomes,
      with no differences significant at P = 0.10. For process of care measures,
      decreases were seen in all groups, with no significant differences in change
      scores. Quality improvement strategies must be evaluated in the appropriate
      setting. Initiatives that have been effective in capitated systems may not be
      effective in fee-for-service environments.

PMID- 16609734
TI  - Invited commentary: Opportunities and challenges in health care equity.

PMID- 16609733
TI  - Improving quality and reducing inequities: a challenge in achieving best care.
AB  - The health care quality chasm is better described as a gulf for certain segments
      of the population, such as racial and ethnic minority groups, given the gap
      between actual care received and ideal or best care quality. The landmark
      Institute of Medicine report Crossing the Quality Chasm: A New Health System for
      the 21st Century challenges all health care organizations to pursue six major
      aims of health care improvement: safety, timeliness, effectiveness, efficiency,
      equity, and patient-centeredness. "Equity" aims to ensure that quality care is
      available to all and that the quality of care provided does not differ by race,
      ethnicity, or other personal characteristics unrelated to a patient's reason for
      seeking care. Baylor Health Care System is in the unique position of being able
      to examine the current state of equity in a typical health care delivery system
      and to lead the way in health equity research. Its organizational vision,
      "culture of quality," and involved leadership bode well for achieving equitable
      best care. However, inequities in access, use, and outcomes of health care must
      be scrutinized; the moral, ethical, and economic issues they raise and the
      critical injustice they create must be remedied if this goal is to be achieved.
      Eliminating any observed inequities in health care must be synergistically
      integrated with quality improvement. Quality performance indicators currently
      collected and evaluated indicate that Baylor Health Care System often performs
      better than the national average. However, there are significant variations in
      care by age, gender, race/ethnicity, and socioeconomic status that indicate the
      many remaining challenges in achieving "best care" for all.

PMID- 16609731
TI  - The expanding universe of prion diseases.
AB  - Prions cause fatal and transmissible neurodegenerative disease. These etiological
      infectious agents are formed in greater part from a misfolded cell-surface
      protein called PrP(C). Several mammalian species are affected by the diseases,
      and in the case of "mad cow disease" (BSE) the agent has a tropism for humans,
      with negative consequences for agribusiness and public health. Unfortunately, the
      known universe of prion diseases is expanding. At least four novel prion diseases
      -including human diseases variant Creutzfeldt-Jakob disease (vCJD) and sporadic
      fatal insomnia (sFI), bovine amyloidotic spongiform encephalopathy (BASE), and
      Nor98 of sheep--have been identified in the last ten years, and chronic wasting
      disease (CWD) of North American deer (Odocoileus Specis) and Rocky Mountain elk
      (Cervus elaphus nelsoni) is undergoing a dramatic spread across North America.
      While amplification (BSE) and dissemination (CWD, commercial sourcing of cervids
      from the wild and movement of farmed elk) can be attributed to human activity,
      the origins of emergent prion diseases cannot always be laid at the door of
      humankind. Instead, the continued appearance of new outbreaks in the form of
      "sporadic" disease may be an inevitable outcome in a situation where the
      replicating pathogen is host-encoded.

PMID- 16609735
TI  - Preoperative exclusion of significant coronary artery disease by 64-slice CT
      coronary angiography in a patient with a left atrial myxoma.

PMID- 16609730
TI  - Identification of a novel Gammaretrovirus in prostate tumors of patients
      homozygous for R462Q RNASEL variant.
AB  - Ribonuclease L (RNase L) is an important effector of the innate antiviral
      response. Mutations or variants that impair function of RNase L, particularly
      R462Q, have been proposed as susceptibility factors for prostate cancer. Given
      the role of this gene in viral defense, we sought to explore the possibility that
      a viral infection might contribute to prostate cancer in individuals harboring
      the R462Q variant. A viral detection DNA microarray composed of oligonucleotides
      corresponding to the most conserved sequences of all known viruses identified the
      presence of gammaretroviral sequences in cDNA samples from seven of 11 R462Q
      homozygous (QQ) cases, and in one of eight heterozygous (RQ) and homozygous wild
      type (RR) cases. An expanded survey of 86 tumors by specific RT-PCR detected the
      virus in eight of 20 QQ cases (40%), compared with only one sample (1.5%) among
      66 RQ and RR cases. The full-length viral genome was cloned and sequenced
      independently from three positive QQ cases. The virus, named XMRV, is closely
      related to xenotropic murine leukemia viruses (MuLVs), but its sequence is
      clearly distinct from all known members of this group. Comparison of gag and pol
      sequences from different tumor isolates suggested infection with the same virus
      in all cases, yet sequence variation was consistent with the infections being
      independently acquired. Analysis of prostate tissues from XMRV-positive cases by
      in situ hybridization and immunohistochemistry showed that XMRV nucleic acid and
      protein can be detected in about 1% of stromal cells, predominantly fibroblasts
      and hematopoietic elements in regions adjacent to the carcinoma. These data
      provide to our knowledge the first demonstration that xenotropic MuLV-related
      viruses can produce an authentic human infection, and strongly implicate RNase L
      activity in the prevention or clearance of infection in vivo. These findings also
      raise questions about the possible relationship between exogenous infection and
      cancer development in genetically susceptible individuals.

PMID- 16609736
TI  - Lymphocytic myocarditis as a cause of fulminant fatal heart failure.

PMID- 16609737
TI  - Heart failure resulting from chemotherapy for testicular neoplasm: a follow-up on
      a patient reported 20 years earlier.

PMID- 16609739
TI  - History of tumor site conferences at Baylor University Medical Center.

PMID- 16609738
TI  - Thyrotoxic periodic paralysis.

PMID- 16609740
TI  - Free and reliable consumer health information for patients.

PMID- 16609741
TI  - Donald Alan Kennerly, MD, PhD: a conversation with the editor.

PMID- 16609742
TI  - Carolyn Maureen Clancy, MD: a conversation with the editor.

PMID- 16609743
TI  - Invited commentary: Baylor Health Care System: sharing the vision of the quality
      challenge.

PMID- 16609744
TI  - Papule on the dorsal foot.

PMID- 16609745
TI  - Wide and narrow QRS complexes after arthroscopy.

PMID- 16609746
TI  - Tigecycline (Tygacil): the first in the glycylcycline class of antibiotics.

PMID- 16609747
TI  - Facts and ideas from anywhere.

PMID- 16609748
TI  - Differences in Adjustment in HIV+ African American Heterosexual and Homosexual
      Women.
AB  - This preliminary study explores differences in adjustment in lesbians and
      heterosexual women by examining three dimensions: psychological distress, major
      depression, and social support. Surveys were administered to 48 participants. HIV
      positive African American lesbians experienced higher levels of psychological
      distress, anxiety, and current major depression than did their heterosexual
      counterparts. Lesbians reported less social support from their immediate family,
      but not from other sources such as friends, compared to the heterosexual women.
      Lesbians also reported less satisfaction with their social support network. The
      results presented here highlight the merit of future research to examine factors
      associated with the lack of family-based social support in HIV-infected lesbians
      and the potential of developing interventions that assess relationships with
      members of the immediate family, explore the possibility of repairing these
      relationships, and capitalize on social support from friends.

PMID- 16609749
TI  - INTERDEPENDENCE OF STRESS PROCESSES AMONG AFRICAN AMERICAN FAMILY MEMBERS:
      INFLUENCE OF HIV SEROSTATUS AND A NEW INFANT.
AB  - This study makes a theoretical contribution to stress process research by using a
      systemic approach to contextualize individual outcomes within the framework of
      other family members' experience. Utilizing a mixed model approach, indicators of
      the stress process of urban low-income HIV(+) African American recent mothers
      were found to affect the psychological distress and perceived adequacy of coping
      of multiple other family members. These relationships were found to be strongest
      proximal to birth and to be exacerbated by HIV infection. Social support to the
      mother was found to have differential effects depending on whether it was from
      the immediate family or outside sources. HIV infection of the recent mother was
      found to affect family members both through relationships of the mother's stress
      process and through their own coping responses.

PMID- 16609750
TI  - The Protective Role of the Family and Social Support Network in a Sample of HIV
      Positive African American Women: Results of a Pilot Study.
AB  - This study examined the role of family functioning and social support in
      protecting HIV-positive African American women from the adverse psychological
      consequences associated with deterioration in their CD4 cell count. Participants
      were 38 African American HIV-positive women who had recently given birth. Results
      demonstrated that changes in CD4 cell counts were inversely predictive of
      psychological distress and were moderated by family functioning and social
      support satisfaction. Women with good family functioning were less affected by
      changes in their CD4 cell counts, and women with poor family functioning were
      more emotionally responsive to changes in CD4 cell count. Unexpectedly, women
      from families where conflicts tended to be clearly laid out and discussed were
      also more responsive to both changes in CD4 cell counts. Interventions are
      recommended that increase a client's social support satisfaction, foster an
      adaptive level of connectedness to family, and enhance the family's range of
      conflict resolution styles.

PMID- 16609751
TI  - The approach to dysplasia surveillance in inflammatory bowel disease.

PMID- 16609752
TI  - The hot air and cold facts of dietary fibre.

PMID- 16609754
TI  - Photodynamic therapy in Barrett's esophagus: results of treatment of 17 patients.
AB  - BACKGROUND: Barrett's esophagus (BE) with dysplasia may progress to esophageal
      adenocarcinoma. Photodynamic therapy is a promising treatment for BE. OBJECTIVE:
      To determine if photodynamic therapy is an acceptable alternative to
      esophagectomy in BE patients with high-grade dysplasia or early adenocarcinoma.
      METHODS: Seventeen patients were treated with photodynamic therapy for BE and
      high-grade dysplasia or early esophageal adenocarcinoma. Patients with residual
      Barrett's epithelium were treated with supplemental argon plasma coagulation or
      potassium titanyl phosphate laser. Patients underwent follow-up endoscopy three,
      six, nine and 12 months post-treatment, then every six to 12 months. Mean follow
      up was 21 months. RESULTS: High-grade dysplasia or early adenocarcinoma was
      completely eliminated in nine of 15 (60%) patients. High-grade dysplasia was
      downgraded in one patient, persisted in one patient and progressed in four
      patients. Two patients with early esophageal adenocarcinoma were nonresponders.
      Complications included stricture, sunburn, urticaria, small pleural effusions,
      esophageal spasm and transient atrial fibrillation. CONCLUSIONS: Photodynamic
      therapy with supplemental ablation is a good, noninvasive therapy for elimination
      of high-grade dysplasia and early adenocarcinoma in BE. Failure to eliminate
      dysplastic epithelium occurred in 40% of the patients, thereby necessitating
      careful follow-up.

PMID- 16609753
TI  - Prognostic factors and survival in patients with hereditary hemochromatosis and
      cirrhosis.
AB  - OBJECTIVES: The survival of treated, noncirrhotic patients with hereditary
      hemochromatosis is similar to that of the general population. Less is known about
      the outcome of cirrhotic hereditary hemochromatosis patients. The present study
      evaluated the survival of patients with hereditary hemochromatosis and cirrhosis.
      METHODS: From an established hereditary hemochromatosis database, all cirrhotic
      patients diagnosed from January 1972 to August 2004 were identified. Factors
      associated with survival were determined using univariate and multivariate
      regression. Survival differences were assessed using the Kaplan-Meier life table
      method. RESULTS: Ninety-five patients were identified. Sixty patients had genetic
      testing, 52 patients (87%) were C282Y homozygotes. Median follow-up was 9.2 years
      (range 0 to 30 years). Nineteen patients (20%) developed hepatocellular
      carcinoma, one of whom was still living following transplantation. Cumulative
      survival for all patients was 88% at one year, 69% at five years and 56% at 20
      years. Factors associated with death on multivariate analysis included advanced
      Child-Pugh score and hepatocellular carcinoma. Patients with hepatocellular
      carcinoma were older at the time of diagnosis of cirrhosis (mean age 61 and 54.6
      years, respectively; P=0.03). The mean age at the time of diagnosis of
      hepatocellular carcinoma was 70 years (range 48 to 79 years). No other
      differences were found between the groups. CONCLUSIONS: Patients with hereditary
      hemochromatosis and cirrhosis are at significant risk of developing
      hepatocellular carcinoma. These patients are older when diagnosed with carcinoma
      and may have poorer survival following transplantation than patients with other
      causes of liver disease. Early diagnosis and treatment of hereditary
      hemochromatosis by preventing the development of cirrhosis may reduce the
      incidence of hepatocellular carcinoma in the future.

PMID- 16609755
TI  - Hydrogen breath test for diagnosis of lactose malabsorption: the importance of
      timing and the number of breath samples.
AB  - BACKGROUND: The hydrogen breath test (H(2)BT) is the most widely used procedure
      in the diagnostic workup of lactose malabsorption and lactose intolerance. AIM:
      To establish whether a simplified two- or three-sample test may reduce time,
      costs and staff resources without reducing the sensitivity of the procedure.
      PATIENTS AND METHODS: Data from 1,112 patients (292 men, 820 women) with a
      positive 4 h, nine-sample H(2)BT were retrospectively analyzed. Patients were
      stratified according to the degree of lactose malabsorption, the occurrence and
      type of symptoms. Loss of sensitivity in the procedure was evaluated taking into
      account two-sample tests (0 min and 120 min or 0 min and 210 min) or three-sample
      tests (0 min, 120 min and 180 min or 0 min, 120 min and 210 min). RESULTS: Using
      a two-sample test (0 min and 120 min or 0 min and 210 min) the false-negative
      rate was 33.4% and 22.7%, respectively. With a three-sample test (0 min, 120 min
      and 180 min or 0 min, 120 min or 210 min), lactose malabsorption was diagnosed in
      91.2% (1,014 of 1,112) patients and in 96.1% (1,068 of 1,112) patients,
      respectively. Of 594 patients with abdominal symptoms, 158 (26.6%) and 73 (12.2%)
      would have false-negative results with 0 min and 120 min or 0 min and 210 min two
      sample tests, respectively. The three-sample tests, 0 min, 120 min and 180 min or
      0 min, 120 min and 210 min, have a false-negative rate of 5.9% and 2.1%,
      respectively. CONCLUSIONS: A three-sample H(2)BT is time- and cost-sparing
      without significant loss of sensitivity for the diagnosis both of lactose
      malabsorption and lactose intolerance.

PMID- 16609756
TI  - Increasing incidence of adenocarcinoma of the gastroesophageal junction and
      distal stomach in Canada -- an epidemiological study from 1964-2002.
AB  - BACKGROUND: The increasing incidence of esophageal and proximal gastric (cardia)
      adenocarcinoma and the decreasing incidence of distal gastric (antropyloric)
      adenocarcinoma has been documented in several populations. The aim of the present
      study was to examine incidence trends of these neoplasms in Ontario, Canada's
      most populous province, over a 39-year period. METHODS: Analyses were based on
      data obtained from the Ontario Cancer Registry of Cancer Care Ontario. Number of
      cases and rates per 100,000 age-adjusted to the 1996 Canadian standard, were
      obtained for all esophageal and gastric carcinoma cases reported between 1964 and
      2002. Rates were grouped into five-year periods to analyze trends over the 39
      year period. Point and 95% CI estimates of average annual percentage change in
      incidence rates were calculated with a log-linear regression model. RESULTS: The
      incidence of adenocarcinoma of the distal esophagus increased in men and women
      (average annual increase of 9.5% in men; 4.3% in women). The incidence of
      adenocarcinoma of the cardia increased in men and women (average annual increase
      of 7.3% in men; 5.8% in women). The incidence of antropyloric adenocarcinoma
      increased in men and women (average annual increase of 4.4% in men; 5.3% in
      women). The incidence of esophageal squamous cell carcinoma remained stable.
      CONCLUSIONS: There has been a significant increase in the incidence of
      adenocarcinoma around the gastroesophageal junction in men over the 39-year study
      period. The increase in incidence of distal gastric adenocarcinoma is unexpected
      and may relate to a reclassification phenomenon, immigration trends in Ontario
      and a rising incidence of diffuse/signet ring cell adenocarcinoma.

PMID- 16609757
TI  - The association of Helicobacter pylori infection and nonsteroidal anti
      inflammatory drugs in peptic ulcer disease.
AB  - BACKGROUND AND AIM: Peptic ulcer disease (PUD) affects 10% of the world
      population. Helicobacter pylori infection and the use of a nonsteroidal anti
      inflammatory drug (NSAID) are the principal factors associated with PUD. The aim
      of the present study was to evaluate a cohort of patients with PUD and determine
      the association between H pylori infection and NSAID use. PATIENTS AND METHODS:
      The medical charts of patients with endoscopic diagnosis of PUD were
      retrospectively reviewed from September 2002 to August 2003. Patients were
      divided into three groups according to ulcer etiology: H pylori infection (group
      1); NSAID use (group 2); and combined H pylori infection and NSAID use (group 3).
      RESULTS: One hundred two patients were evaluated: 36 men (35.3%) and 66 women
      (64.7%). Forty patients had H pylori infection, 43 had used NSAIDs and 15 had
      combined H pylori infection and NSAID use; four patients with ulcers secondary to
      malignancy were excluded. The frequency of women was significantly higher in
      group 2 (P=0.01). The mean age of patients in group 1 was significantly lower
      than in the other two groups (P=0.003). PUD developed earlier in group 3 than in
      group 2 (5.0+/-4.7 months versus 1.4+/-2.1 months, respectively, P=0.018). Thirty
      two patients (32.7%) had bleeding peptic ulcer. Group 2 had a higher risk of
      bleeding peptic ulcer than the other two groups (P=0.001). CONCLUSIONS: The
      development of PUD was observed earlier in the combined H pylori and NSAID group
      than in patients with only NSAID use. This suggests a synergic effect between the
      two risks factors in the development of PUD.

PMID- 16609758
TI  - Canadian physicians' choices for their own colon cancer screening.
AB  - INTRODUCTION: Compliance with colorectal cancer (CRC) screening in Canada is low.
      The aim of the present survey was to determine whether Canadian physicians older
      than 50 years were pursuing colon cancer screening. Specifically, physicians were
      asked to identify their modality of choice and identify their barriers to
      screening. METHODS: Surveys were mailed to members, older than 50 years, of the
      Canadian Association of Gastroenterology, the Society of Obstetricians and
      Gynaecologists of Canada, the Canadian Society of Internal Medicine, the Canadian
      Psychiatric Association and the Canadian Association of Radiologists. RESULTS: Of
      2,807 surveys, 46% were returned. Screening for CRC was reported by 53% of
      respondents. The Canadian Association of Radiologists members (61%) and the
      Canadian Association of Gastroenterology members (61%) were more likely to be
      screened than other specialties (P<0.01 and P<0.05, respectively). Members of the
      Society of Obstetricians and Gynaecologists of Canada (44%) were least likely to
      be screened (P<0.001). Men (P<0.001) and Ontario physicians (P<0.01) were more
      likely to be screened than women and Canadian physicians from other provinces,
      respectively. Colonoscopy (56%) was the most common screening modality used,
      followed by fecal occult blood testing (27%). Respondents who had not been
      screened cited a lack of personal time (47%) and insufficient data to warrant
      screening (14%). DISCUSSION: More than one-half of all respondents were screened
      for CRC. Colonoscopy is the most common screening modality used. Lack of time is
      the most common reason cited for not participating in CRC screening.

PMID- 16609759
TI  - Spontaneous intramural esophageal hematoma: case report and review.
AB  - Intramural esophageal hematoma is a rare form of esophageal injury. The
      presenting symptoms are nonspecific. Esophagogastroscopy and computed tomography
      scan are usually needed to establish the diagnosis of intramural esophageal
      hematoma. Presented here is a patient with spontaneous intramural esophageal
      hematoma who was successfully treated with conservative measures.

PMID- 16609760
TI  - A case of rectal Dieulafoy's ulcer and successful endoscopic band ligation.
AB  - Dieulafoy's ulcer is a rare cause of gastrointestinal bleeding. The lesion is
      usually located in the stomach, although it may occur anywhere in the
      gastrointestinal tract. A 44-year-old man was admitted to hospital due to
      cerebral infarction. On the 23rd day of hospitalization, he showed massive
      hematochezia. He underwent an urgent colonoscopy. There was a visible protuberant
      vessel without significant ulceration at the fundus of the rectum, consistent
      with a Dieulafoy's ulcer. It was treated by endoscopic hemoclipping. However,
      rebleeding occurred three times despite repeated hemoclipping. Finally,
      endoscopic band ligation was successfully performed to achieve permanent
      hemostasis. Endoscopic band ligation is an effective treatment for bleeding
      rectal Dieulafoy's ulcer.

PMID- 16609761
TI  - Chronic urticaria: a cutaneous manifestation of celiac disease.
AB  - Celiac disease, or gluten-sensitive enteropathy, is an immune-mediated disease of
      the small bowel that results in malabsorption. It classically presents with
      gastrointestinal symptoms including chronic diarrhea, weight loss, abdominal
      bloating and anorexia. It is becoming more frequently identified in asymptomatic
      patients with a diagnosis of deficiencies related to malabsorption of iron, folic
      acid, vitamin B12 and vitamin D. It is increasingly identified as a cause for
      early or refractory osteoporosis. Occasionally, celiac disease presents with
      cutaneous manifestations alone. Dermatitis herpetiformis is a well-recognized
      cutaneous manifestation of celiac disease. Other cutaneous manifestations include
      alopecia, angular stomatitis and aphthous ulcerations. Described here is a case
      of a 24-year-old woman who presented with intermittent urticaria and
      gastrointestinal complaints. She was found to have celiac disease on small-bowel
      biopsy. Both her gastrointestinal symptoms and urticaria resolved when she was
      put on a gluten-free diet, suggesting that her urticaria was a cutaneous
      manifestation of celiac disease.

PMID- 16609762
TI  - Metal-based antitumour drugs in the post genomic era.
AB  - The discovery of new metal-based antitumour drugs, whether cisplatin derivatives
      or those based on other metals, has been largely based on cell viability assays
      (IC50 values) and compounds that bind to DNA. This approach has been applied for
      more than 30 years during which time very few new drugs have entered clinical
      use. In this article we discuss what the future holds for metal-based drugs, in
      particular anti-metastasis drugs, in these enlightened times of the post genomic
      era.

PMID- 16609764
TI  - Film growth precursor development for metal nitrides. Synthesis, structure, and
      volatility of molybdenum(VI) and tungsten(VI) complexes containing
      bis(imido)metal fragments and various nitrogen donor ligands.
AB  - The molybdenum and tungsten complexes W2(NtBu)4(pz)4(pzH).(C6H14)0.5 (pz =
      pyrazolate), M(NtBu)2(Me2pz)2(Me2pzH)2 (Me2pz = 3,5-dimethylpyrazolate),
      M(NtBu)2(tBu2pz)2 (tBu2pz = 3,5-di-tert-butylpyrazolate), M2(NtBu)4(Me2pz)2Cl2,
      W(NtBu)2(C2N3(iPr)2)2py2, M(NtBu)2-(CN4CF3)2py2, and W(NtBu)2(PhNNNPh)2 were
      prepared by various synthetic routes from the starting materials Mo(NtBu)2Cl2,
      W(NtBu)2(NHtBu)2, and W(NtBu)2Cl2py2. These new complexes were characterized by
      spectral and analytical methods and by X-ray crystal structure determinations.
      The volatilities and thermal stabilities were evaluated to determine the
      potential of the new complexes for use in thin film growth of metal nitride
      films. Mo(NtBu)2(tBu2pz)2 and W(NtBu)2(tBu2pz)2 were found to have the optimum
      combination of volatility and thermal stability for application in atomic layer
      deposition thin film growth procedures.

PMID- 16609763
TI  - New polyethyleneglycol-functionalized texaphyrins: synthesis and in vitro
      biological studies.
AB  - The synthesis of four new analogues of motexafin gadolinium (MGd), a
      gadolinium(III) texaphyrin complex in clinical trials for its anticancer
      properties, is described. These new derivatives contain either 1,2-diaminobenzene
      or 2,3-diaminonaphthalene subunits as the source of the imine nitrogens and bear
      multiple 2-[2-(2-methoxyethoxy)ethoxy]ethoxy (PEG) groups, on either meso aryl or
      beta-pyrrolic substituents, to increase their water solubility. All four
      analogues were found to be more active in vitro than the parent system MGd as
      judged from cell proliferation assays using the PC3 and A549 cell lines.

PMID- 16609765
TI  - Metal-metal interactions in dinuclear ruthenium complexes containing bridging 4,5
      di(2-pyridyl)imidazolates and related ligands.
AB  - The dinuclear bis(2,2'-bipyridine)ruthenium complex of 4,5-di(2
      pyridyl)imidazolate has been prepared and separated into its (meso and rac)
      diastereoisomers. The 2-phenyl substituted analogue forms the meso isomer
      selectively. All three complexes have been characterised by 1H NMR and X-ray
      crystallography. Electrochemical measurements and spectroelectrochemistry of the
      mixed-valence states reveal strong metal-metal interactions and IVCT bands that
      are highly dependent on the electrolyte.

PMID- 16609766
TI  - Aggregation tendency and reactivity toward AgX of cationic half-sandwich
      ruthenium(II) complexes bearing neutral N,O-ligands.
AB  - The aggregation tendency of complexes [Ru(eta6-cymene)(N,O)Cl]X [N,O = 2
      benzoylpyridine (2-bzpy), 1, and 2-acetylpyridine (2-acpy), 2, X- = BPh4- or PF6
      ] has been studied by means of PGSE NMR experiments. It was found that complexes
      with PF6- as counterion are mainly present in CD2Cl2 as ion pairs at low
      concentration, as a mixture of ion triples and free anions at medium
      concentration and as ion quadruples at elevated concentration. 19F, 1H-HOESY NMR
      experiments revealed that in ion triples and ion quadruples two cationic Ru-units
      pair up. Consistently, in the solid-state structure of 1PF6, determined through X
      ray single-crystal investigation, two cationic Ru-units are held together by an
      intermolecular pi-pi stacking interaction between the pyridyl rings. Complexes
      having BPh4- as counterion are only present in solution as even aggregates,
      namely ion pairs at low concentration and ion quadruples at elevated
      concentration. In such a case a counteranion bridges two cationic Ru-units as
      observed in the solid-state structure of 1BPh4. The reactivity of complexes 1-2
      toward AgX salts has been investigated in different solvents. Bicationic [Ru(eta6
      cymene)(N,O)(MeCN)]X2 (N,O = 2-bzpy, 3, and 2-acpy, 4) and [Ru(MeCN)4(N,O)]X2
      (N,O = 2-bzpy, 5, and 2-acpy, 6) complexes were obtained by the reaction of 1 and
      2 with AgX in the presence of three equivalents of acetonitrile or in
      acetonitrile, respectively. The reaction of 1 with AgPF6 in acetone afforded
      complex [Ru(eta6-cymene)(N,O,O)]PF6 (7, where N,O,O = 4-alcoxide-4-phenyl-4
      (pyridin-2-yl)butan-2-one) from the C-C coupling of a deprotonated methyl group
      of the coordinated acetone and the C=O moiety of 2-bzpy ligand.

PMID- 16609767
TI  - A series of metal-organic polymers assembled from MCl2 (M = Zn, Cd, Co, Cu):
      structures, third-order nonlinear optical and fluorescent properties.
AB  - In this paper four metal-organic polymers {[Zn(fcz)Cl2].CH3OH}n 1,
      {[Cd(fcz)2Cl2].CH3OH.2H2O}n 2, {[Co(fcz)2Cl2].2CH3OH}n 3 and
      {[Cu(fcz)2Cl2].2CH3OH}n 4 (fcz = fluconazole: alpha-(2,4-difluorophenyl)-alpha
      (1H-1,2,4-triazol-l-ylmethyl)-1H-1,2,4-triazole-l-ethanol) were synthesized and
      characterized by X-ray single crystal diffraction. Polymer consists of 1-D
      infinite chains arranged along the b-axis. All of polymers 2-4 exhibit a 2-D
      rhombohedral grid structure. We study the third-order nonlinear optical
      properties of fcz and polymers 1-4 in DMF solution by using 8 ns laser pulses at
      532 nm, and find that 1 and 4 exhibit different NLO properties from fcz and both
      2 and 3 show similar NLO properties to fcz. 1 possesses strong NLO refractive
      effects and large NLO absorptive behaviors. 2, 3 and fcz exhibit strong
      refractive effects, but their NLO absorptive behaviors are weaker than that of 1.
      The NLO effects of 4 are very weak. The study of optical limiting (OL) effects by
      using 40 ps laser pulses at 532 nm shows that fcz and polymer 3 possess a strong
      OL effect. The optical limiting threshold values of 0.15 J cm(-2) for fcz and
      0.16 J cm(-2) for are comparable to those of many heterothiometallate clusters.
      Polymers 1, 2 and 4 show a weak OL effect. The fluorescent spectra in DMF
      solution (concentration: 1 x 10(-4) mol dm(-3)) show that polymers 1-4 exhibit
      different luminescence properties from fcz. The maximum wavelength of polymers 1
      3 are blue shifted gradually by 2-12 nm while polymer 4 exhibits a fluorescent
      self-quenching phenomenon. These results demonstrate that metal ions play an
      important part in the NLO and fluorescent properties of coordination polymers.

PMID- 16609768
TI  - Polynuclear vanadium complexes from thermal decomposition of
      [V3O(O2CPh)6(H2O)3]Cl.
AB  - Solid-state decomposition of [V3O(O2CPh)6(H2O)3]Cl at 300 degrees C followed by
      alcoholysis of the product gives the new vanadium complexes
      [V6O6(PhCO2)6(CH3O)6(CH3OH)3] (1), [V6O6(PhCO2)6(C2H5O)6(C2H5OH)3] (2),
      [V6O6(PhCO2)6(C3H7O)6(C3H7OH)3] (3), [V6O6(PhCO2)6(C4H9O)6(C4H9OH)3] (4) and
      [V4O4(OCH3)6(O2CPh)2(HOCH3)2] (5). Complexes 2, 3 and 5 have been
      crystallographically characterised. DC magnetic susceptibility studies on complex
      shows antiferromagnetic coupling leading to a S = 0 spin ground state.

PMID- 16609769
TI  - Quasi-one-dimensional molecular magnets based on derivatives of
      (fluorobenzyl)pyridinium with the [M(mnt)2] monoanion (M = Ni, Pd or Pt; mnt2- =
      maleonitriledithiolate): syntheses, crystal structures and magnetic properties.
AB  - The syntheses, structural characterizations and magnetic behaviors of three new
      complexes, 1-(3',4',5'-trifluorobenzyl)pyridinium [M(mnt)2]- [M = Ni (1), Pd (2)
      or Pt (3)], are reported. These complexes are isomorphous and their prominent
      structural character is that the [M(mnt)2]- anions form columnar stacks, in which
      the dimerization was observed. Complexes 2 and 3 are diamagnetic, while 1
      possesses an energy gap of 2474 K. For crystal 4, 1-(4'-fluorobenzyl)pyridinium
      [Ni(mnt)2] (its structure and magnetic susceptibility were briefly reported
      earlier), the magnetic behavior can be divided into two regimes, namely, weakly
      ferromagnetic coupling above 93 K and strongly antiferromagnetic coupling below
      93 K. A transition occurs at 93 K which switches the magnetic exchange nature
      from ferromagnetic to antiferromagnetic. A sharp thermal abnormality with lambda
      shape, associated with the transition, appears from its heat capacity measurement
      to indicate that the transition is first order. The temperature dependences of
      the superlattice diffractions revealed the existence of the pretransitional
      phenomena up to at least 140 K. The unusual magnetic behavior of 4, such as the
      origin of the ferromagnetic interaction in the high temperature phase and what
      causes the spin transition, are discussed further.

PMID- 16609770
TI  - Monomeric lithium triazapentadienyl complexes.
AB  - Treatment of 1,3,5-triazapentadienes [N{(C3F7)C(Mes)N}2]H and
      [N{(C3F7)C(Dipp)N}2]H (where Mes = 2,4,6-Me3C6H2; Dipp = 2,6-Pr(i)2C6H3) with n
      BuLi in hexane, followed by the crystallization from hexane-THF mixture afforded
      the corresponding lithium 1,3,5-triazapentadienyl complexes as their THF
      solvates. X-Ray crystallographic analyses revealed that
      [N{(C3F7)C(Mes)N}2]Li(THF)2 and [N{(C3F7)C(Dipp)N}2]Li(THF) are monomeric in the
      solid state. [N{(C3F7)C(Mes)N}2]Li(THF)2 has a four-coordinate lithium center
      with a distorted tetrahedral geometry, and features a boat-shaped C2N3Li
      metallacycle. [N{(C3F7)C(Dipp)N}2]Li(THF) has a three-coordinate lithium atom and
      a planar, U-shaped C2N3 ligand backbone. The synthesis, solid-state structure,
      and 1H and 19F NMR spectroscopic details of [N{(C3F7)C(Mes)N}2]H are also
      reported.

PMID- 16609771
TI  - The amide oxygen donor. Metal ion coordinating properties of the ligand
      nitrilotriacetamide. A thermodynamic and crystallographic study.
AB  - The metal ion coordinating properties of ntam (nitrilotriacetamide) are reported.
      The protonation constant (pK) for ntam is 2.6 in 0.1 M NaClO(4) at 25 degrees C.
      Formation constants (log K(1)) in 0.1 M NaClO(4) at 25 degrees C, determined by
      (1)H NMR and UV-Vis spectroscopy are: Ca(II), 1.28; Mg(II), 0.4; La(III), 2.30;
      Pb(II), 3.69; Cd(II), 3.78; Ni(II), 2.38; Cu(II), 3.16. The measured log K(1)
      values for the ntam complexes are discussed in terms of the low basicity of the N
      donor, as evidenced by the pK, and the effect of metal ion size on complex
      stability. The amide O-donors of ntam lead to the stabilization of complexes of
      large metal ions (Pb(II), Cd(II), La(III), Ca(II)) relative to log K1 for the NH3
      complexes, while for small metal ions (Ni(II), Cu(II)) the amide O-donors lead to
      destabilization. This is discussed in terms of the role of chelate ring size in
      controlling metal ion size-based selectivity. The structures of [Pb(ntam)(NO3)2]2
      (1) and [Ca2(ntam)3(H2O)2](ClO4)4.3H2O (2) are reported. For 1: triclinic, space
      group P1, a = 7.4411(16), b = 9.0455(19), c = 11.625(3) A, alpha = 69.976(4),
      beta = 79.591(4), gamma = 67.045(3) degrees, Z = 2, R = 0.0275. For 2:
      monoclinic, space group P2(1)/c, a = 10.485(2), b = 11.414(2), c = 38.059(8) A,
      beta = 92.05(3) degrees, Z = 4, R = 0.0634. Structure 1 is dimeric with two Pb
      atoms linked by bridging O-donors from the two ntam ligands. The coordination
      sphere consists of one N-donor and 3 O-donors from the ntam ligand, two O-donors
      from nitrates, and one bridging O-donor. The variation in bond length suggests a
      stereochemically active lone pair of electrons on the Pb. Structure 2 consists of
      two Ca(II) ions held together by 3 bridging O-donors from ntam groups. One Ca is
      9-coordinate with two ntam ligands present, plus one bridging O-donor from the
      other Ca(II) ntam complex. The other Ca is 8-coordinate, with a single
      coordinated ntam, plus two coordinated H2O molecules, and two bridging O-donors
      from the other half of the complex. The role of M-O=C bond angles in controlling
      selectivity for metal ions on the basis of their size is discussed.

PMID- 16609773
TI  - Periodic trends in metal-metal interactions in face-shared [M2Cl9]z- systems.
AB  - The periodic trends in metal-metal interactions in even-electron and mixed
      valence [M2Cl9]z- face-shared systems, involving transition metals in Groups 4 to
      8 and electronic configurations ranging from d1d1 through to d5d5 and from d1d2
      through to d4d5, have been investigated by calculating metal-metal bonding and
      spin polarization (exchange) effects using density functional theory. These two
      terms are in opposition to one another and their relative difference determines
      the extent to which the metal-based electrons are delocalized and thus the degree
      of metal-metal bonding. Remarkably strong linear correlations between the two
      terms, and between each term and the square of the spin density on the metal
      centres, have been obtained for all group and period series considered, and are
      discussed in terms of their dependence on the metal orbital properties and
      electron density.

PMID- 16609772
TI  - Isomerization and fragmentation reactions of gaseous phenylarsane radical cations
      and phenylarsanyl cations. A study by tandem mass spectrometry and theoretical
      calculations.
AB  - The unimolecular reactions of radical cations and cations derived from
      phenylarsane, C6H5AsH2 (1) and dideutero phenylarsane, C6H5AsD2 (1-d2), were
      investigated by methods of tandem mass spectrometry and theoretical calculations.
      The mass spectrometric experiments reveal that the molecular ion of phenylarsane,
      1*+, exhibits different reactivity at low and high internal excess energy. Only
      at low internal energy the observed fragmentations are as expected, that is the
      molecular ion 1*+ decomposes almost exclusively by loss of an H atom. The
      deuterated derivative 1-d2 with an AsD2 group eliminates selectively a D atom
      under these conditions. The resulting phenylarsenium ion [C6H5AsH]+, 2+,
      decomposes rather easily by loss of the As atom to give the benzene radical
      cation [C6H6]*+ and is therefore of low abundance in the 70 eV EI mass spectrum.
      At high internal excess energy, the ion 1*+ decomposes very differently either by
      elimination of an H2 molecule, or by release of the As atom, or by loss of an AsH
      fragment. Final products of these reactions are either the benzoarsenium ion 4*+,
      or the benzonium ion [C6H7]+, or the benzene radical cation, [C6H6]*+. As key
      steps, these fragmentations contain reductive eliminations from the central As
      atom under H-H or C-H bond formation. Labeling experiments show that H/D exchange
      reactions precede these fragmentations and, specifically, that complete
      positional exchange of the H atoms in 1*+ occurs. Computations at the UMP2/6
      311+G(d)//UHF/6-311+G(d) level agree best with the experimental results and
      suggest: (i) 1*+ rearranges (activation enthalpy of 93 kJ mol(-1)) to a
      distinctly more stable (DeltaH(r)(298) = -64 kJ mol(-1)) isomer 1 sigma*+ with a
      structure best represented as a distonic radical cation sigma complex between AsH
      and benzene. (ii) The six H atoms of the benzene moiety of 1 sigma*+ become
      equivalent by a fast ring walk of the AsH group. (iii) A reversible isomerization
      1+<==>1 sigma*+ scrambles eventually all H atoms over all positions in 1*+. The
      distonic radical cation 1*+ is predisposed for the elimination of an As atom or
      an AsH fragment. The calculations are in accordance with the experimentally
      preferred reactions when the As atom and the AsH fragment are generated in the
      quartet and triplet state, respectively. Alternatively, 1*(+) undergoes a
      reductive elimination of H2 from the AsH2 group via a remarkably stable complex
      of the phenylarsandiyl radical cation, [C6H5As]*+ and an H2 molecule.

PMID- 16609774
TI  - Design of base metal extractants. Part 1. Inter-ligand hydrogen bonding in the
      assembly of pseudo-macrocyclic bis(aminosulfonamidato)M(II) complexes.
AB  - Monosulfonyl derivatives of simple 1,2- and 1,3-diamines (R2HN-R-NHSO2R1 = L)
      have been shown to be easily deprotonated to give neutral 2:1 complexes, [M(L -
      H)(2)], with Co(II), Ni(II), Cu(II) or Zn(II). The Ni(II) and Cu(II) complexes
      with deprotonated N-tosyl-1,2-diaminoethane have a planar N4(2-) donor set and a
      14-membered pseudo-macrocyclic structure based on head-to-tail S=O...H-N((amine))
      bonding between the two bidentate ligands. In the related tetrahedral Zn(II)
      complex the ends of the mutually perpendicular bidentate N2- units are too far
      apart to form a cyclic H-bonded system. X-Ray structure determinations on five
      free ligands provide evidence for extensive inter-molecular H-bonding, which in
      the case of N-tosyl-1,3-diaminopropane and its N'-tert-butyl derivative involves
      formation of dimeric 16-membered pseudo-macrocycles. Despite favourable inter
      ligand H-bonding in the neutral 2:1 complexes, these ligands are relatively weak
      extractants, showing >50% loading of Cu(II) in "pH-swing" equilibria, 2L(org)+
      M2+ = [M(L - H)2](org)+ 2 H+, only when the pH of the aqueous phase is raised
      above 4.

PMID- 16609775
TI  - Crystal engineering of binary metal imidazolate and triazolate frameworks.
AB  - This article summarizes the recent advances in the crystal growth, structural
      control strategies and diverse structures of the binary metal imidazolate and
      triazolate frameworks, which are the simplest systems for crystal engineering of
      two-, three- and four-connected coordination polymers.

PMID- 16609776
TI  - Bisphosphine based hetero-capsules for the encapsulation of transition metals.
AB  - Just mixing of solutions of tetracationic diphosphine ligands and tetraanionic
      calix[4]arene building blocks leads to the formation of supramolecular
      heterocapsules that coordinate a palladium metal within the cavity of the
      assembly, giving rise to a new class of potential supramolecular transition metal
      catalysts.

PMID- 16609777
TI  - Nanoscale electrocrystallisation of Sb and the compound semiconductor AlSb from
      an ionic liquid.
AB  - Aluminium antimonide nanoclusters with an apparent band gap energy of 0.92 +/-
      0.2 eV have been electrodeposited from the neutral ionic melt AlCl3-1-butyl-3
      methylimidazolium chloride {AlCl3-[C4mim]+Cl-} at room temperature and have been
      characterized in-situ by electrochemical scanning tunneling microscopy (STM) and
      spectroscopy (STS).

PMID- 16609778
TI  - A10Tl6O2 (A = K, Rb) cluster compounds combining structural features of thallium
      cluster anions and of alkali metal sub-oxides.
AB  - New alkali metal thallideoxides, A10Tl6O2 (A = K, Rb), crystallize in a unique
      structure consisting of hypoelectronic [Tl6]6- clusters in the shape of
      compressed octahedra, together with oxygen-centred alkali metal octahedra that
      have been identified as constitutive of alkali metal sub-oxides.

PMID- 16609779
TI  - Desorption electrospray ionization with a portable mass spectrometer: in situ
      analysis of ambient surfaces.
AB  - Desorption electrospray ionization (DESI) is implemented on a portable mass
      spectrometer and used to demonstrate in situ detection of active ingredients in
      pharmaceutical preparations, alkaloids in plant tissues, explosives, chemical
      warfare agent simulants and agricultural chemicals from a variety of surfaces;
      air monitoring applications using DESI are also introduced.

PMID- 16609780
TI  - The first supramolecular photosensitization of enantiodifferentiating bimolecular
      reaction: anti-Markovnikov photoaddition of methanol to 1,1-diphenylpropene
      sensitized by modified beta-cyclodextrin.
AB  - Enantiodifferentiating polar photoaddition of methanol to 1,1-diphenylpropene
      included and sensitized by cyanonaphthalene-modified beta-cyclodextrin was
      examined for the first time to give optically active anti-Markovnikov adduct with
      accompanying inversion of the chiral sense of the photoproduct by temperature,
      which is entropic in origin.

PMID- 16609781
TI  - Liquid/liquid separation of polysiloxane-supported catalysts.
AB  - Liquid/liquid separation after monophasic reactions is a viable way to use and
      recover polysiloxane-supported catalysts.

PMID- 16609782
TI  - A non-heme dinuclear iron(II) complex containing a single, unsupported hydroxo
      bridge.
AB  - Complexation of the tetrapodal pentadentate NN4 ligand 2,6-C5H3N[CMe(CH2NH2)2]2
      (I) with iron(II) perchlorate hydrate in methanol, in the presence of N
      methylimidazole, produces a diferrous complex with a single, unsupported mu-OH
      ligand between two {(I)FeII} coordination modules.

PMID- 16609783
TI  - Building three-dimensional nanostructures with active enzymes by surface
      templated layer-by-layer assembly.
AB  - We show that well-defined three-dimensional nanostructures of functional enzymes
      can be controllably fabricated by layer-by-layer assembly of avidin and
      biotinylated horseradish peroxidase on micro-contact printing patterned surface
      templates.

PMID- 16609784
TI  - Solvent-tunable inversion of chirality transfer from carbon to copper.
AB  - A change of solvent causes an inversion of the stereochemistry at copper of the
      chiral Cu(I) complex described herein.

PMID- 16609785
TI  - Dynamic covalent polymers based upon carbene dimerization.
AB  - Thermally-reversible covalent polymers featuring dynamic carbon-carbon double
      bonds and tunable molecular weights were prepared from difunctional carbenes;
      addition of transition metal complexes to these materials afforded the respective
      main-chain organometallic polymers.

PMID- 16609786
TI  - Efficient preparation and improved sensitivity of molecularly imprinted polymers
      using room temperature ionic liquids.
AB  - Synthesis of trans-aconitic acid molecularly imprinted polymers in [bmim][BF4]
      and [bmim][PF6] under photochemical (5 degrees C, AIBN) and thermal (60 degrees
      C, AIBN) conditions gave polymer micro-spheres (<200 nm), under bulk and
      precipitation polymerisation conditions, and higher selectivity indices (100%
      improvement) relative to the more traditional precipitation polymerisation
      (CH3CN, high solvent volumes) approach.

PMID- 16609787
TI  - Conductive polymer-carbon-imidazolium composite: a simple means for constructing
      solid-state dye-sensitized solar cells.
AB  - A clay-like conductive material comprising polyaniline-loaded carbon black
      particles and an ethyleneoxide-substituted imidazolium iodide was prepared. The
      material was sandwiched between dye-coated porous TiO2 and counter-electrode to
      form a solid-state dye-sensitized solar cell, which works with overall conversion
      efficiencies of 3.48% and 4.07% for AM 1.5, 100 mW cm(-2) and 23 mW cm(-2)
      irradiation, respectively.

PMID- 16609788
TI  - Preparation of PEO-b-P2VPH+-S2O8(2-) micelles in water and their reversible UCST
      and redox-responsive behavior.
AB  - We report here the preparation of PEO-b-P2VPH+-S2O8(2-) micelles and their
      reversible multi-responsive behavior.

PMID- 16609789
TI  - Remarkable ligand effect on the palladium-catalyzed double carbonylation of aryl
      iodides.
AB  - The use of t-Bu3P as a ligand dramatically improved the generality of the double
      carbonylation of aryl iodides, and Mo(CO)6 was also found to be effective as a CO
      source in the system.

PMID- 16609791
TI  - An iron(III) phosphonate cluster containing a nonanuclear ring.
AB  - This communication reports the first example of cyclic ferric clusters with an
      odd number of iron atoms capped by phosphonate ligands, namely, [Fe9(mu-OH)(7)(mu
      O)2(O3PC6H9)8(py)12]. The magnetic studies support a S = 1/2 ground state with an
      exchange coupling constant of about J approximately equal to -30 K.

PMID- 16609790
TI  - Possibility of a non-amino acid pathway in the biosynthesis of marine-derived
      oxazoles.
AB  - A novel avenue for oxazoles via Beckmann rearrangement of alpha-formyl ketoxime
      dimethyl acetals is described that indicates the possibility of a non-amino acid
      biosynthetic pathway in marine natural products.

PMID- 16609792
TI  - Broadband dielectric response of the ionic liquid N-methyl-N-ethylpyrrolidinium
      dicyanamide.
AB  - Dielectric relaxation measurements as a function of temperature, and of
      concentration in a non-coordinating solvent, the first reported for an ionic
      liquid, indicate a crossover in the relaxation mechanism due to varying levels of
      ion aggregation and the interplay of formation kinetics and relaxation dynamics
      of associates.

PMID- 16609793
TI  - A quinhydrone-type 2 ratio 1 acceptor-donor charge transfer complex obtained via
      a solvent-free reaction.
AB  - A 2 : 1 2-methoxybenzoquinone (BQ(OMe))-hydroquinone (H2Q) complex (5), obtained
      as single crystals by a solvent-free reaction, combines dipolar and pi-pi
      interactions, as well as hydrogen bonding.

PMID- 16609794
TI  - A fluorescence polarisation molecular imprint sorbent assay for 2,4-D: a non
      separation pseudo-immunoassay.
AB  - The first pseudo-immunoassay which employs a molecularly imprinted receptor and a
      fluorescent probe, and quantifies the bound analyte directly using the
      fluorescence anisotropy of the polymer-probe-analyte suspension, is described.

PMID- 16609795
TI  - Synthesis of chiral cyclic oligothiazolines: a novel structural motif for a
      macrocyclic molecule.
AB  - The synthesis of chiral cyclic oligo(4-beta-methyl)thiazolines is described;
      linear oligothiazolines were efficiently prepared by the iterative formation of a
      thiazoline ring and a two-directional block condensation, and construction of 24-
      to 36-membered cyclic oligothiazoline systems could be achieved by the head-to
      tail cyclooligomerization of doubly deprotected linear fragments and subsequent
      thiazoline formation.

PMID- 16609797
TI  - Formation of aluminacyclobutenes via carbon monoxide and isocyanide insertion.
AB  - Reaction of LAl[eta2-(CSiMe3)2] (L = HC[(CMe)(NAr)]2, Ar = 2,6-iPr2C6H3) with
      carbon monoxide and tert-butyl isocyanide afforded unique AlC3
      aluminacyclobutenes via insertion into one of the aluminium-carbon bonds.

PMID- 16609796
TI  - Direct catalytic asymmetric anti-selective Mannich-type reactions.
AB  - The simple chiral pyrrolidine catalyzed asymmetric anti-selective Mannich-type
      reaction is presented; the reaction gives the corresponding amino acid
      derivatives with 10:1- >19:1 dr and 97-99% ee.

PMID- 16609798
TI  - Asymmetric transfer hydrogenation of imines and iminiums catalyzed by a water
      soluble catalyst in water.
AB  - The first asymmetric transfer hydrogenation of cyclic imines and iminiums in
      water was successfully performed in high yields and enantioselectivities with
      sodium formate as the hydrogen source and CTAB as an additive catalyzed by a
      water-soluble and recyclable ruthenium(II) complex of the ligand (R,R)-2.

PMID- 16609799
TI  - Catalytic cracking of large molecules over hierarchical zeolites.
AB  - A hierarchical zeolite catalyst was synthesized by transforming the skeletons of
      a bimodal pore silica gel into a zeolite through a steam-assisted conversion
      method, and shows high catalytic activity and a long catalyst lifetime for
      catalytic cracking of large molecules.

PMID- 16609800
TI  - Nanocast mesoporous MgAl2O4 spinel monoliths as support for highly active gold CO
      oxidation catalyst.
AB  - Mesoporous MgAl2O4 spinel monolith was synthesized by the nanocasting pathway;
      high activity in CO oxidation was observed over gold catalysts based on such
      monoliths as support.

PMID- 16609801
TI  - Cyanide ion cocatalysis in Ti(salen) catalysed asymmetric cyanohydrin carbonate
      synthesis.
AB  - In the presence of potassium cyanide or the potassium cyanide/18-crown-6 complex
      as a cocatalyst, 1-2 mol% of titanium(salen) complex catalyses the asymmetric
      addition of achiral cyanoformates to aldehydes, giving cyanohydrin carbonates
      with high enantiomeric excesses; and catalyses the diastereoselective addition of
      chiral cyanoformates derived from alpha-methylbenzyl alcohol to aldehydes, a
      reaction which exhibits double asymmetric induction.

PMID- 16609802
TI  - Preparation, crystallographic characterization and theoretical study of two
      isomers of C70(CF3)12.
AB  - Two isomers of C70(CF3)12 have been isolated from a mixture obtained by
      trifluoromethylation of C70 with CF3I; their molecular structures determined by X
      ray crystallography are in good agreement with the results of theoretical DFT
      calculations for the most stable C70(CF3)12 isomers.

PMID- 16609803
TI  - A lag-phase in the reduction of flavin dependent thymidylate synthase (FDTS)
      revealed a mechanistic missing link.
AB  - An unexpected substrate-dependent lag-phase, found in the single turnover
      reduction of FDTS bound flavin, sheds light on the molecular mechanism of this
      alternative thymidylate synthase.

PMID- 16609804
TI  - Controlling the oxidation state of arsenic in cyclic arsenic cations.
AB  - Reduction of AsCl3 with SnCl2, followed by treatment of the "AsCl" with a 1,4
      diimine results in electron transfer and formation of an arsenic(III) salt, while
      treatment of this arsenic(I) reagent or AsI3 with an alpha,alpha'-diiminopyridine
      ligand forms an arsenic(I) salt.

PMID- 16609805
TI  - Isolated Hypoglossal nerve palsy due to amyloid cervical arthropathy in long term
      hemodialysis.

PMID- 16609806
TI  - Spinocerebellar ataxia type 2 olfactory impairment shows a pattern similar to
      other major neurodegenerative diseases.
AB  - Olfactory function is affected in different neurodegenerative diseases. Recently,
      it has been found that some hereditary ataxias are also associated with
      significant olfactory impairment. However, the initial findings did not examine
      the nature of the olfactory impairment associated with these ataxias. In the
      present article the effect of spinocerebellar ataxia type 2 (SCA2) on olfactory
      function was studied in 53 SCA2 patients and 53 healthy control subjects from
      Holguin, Cuba. Several tests were applied to evaluate olfactory threshold,
      description, identification and discrimination. The results show significant
      impairment in SCA2 patients on all olfactory measurements, and the pattern of
      olfactory deficits found suggests that they have much in common with those
      reported for other neurodegenerative diseases such as Parkinson's and Alzheimer's
      diseases.

PMID- 16609807
TI  - CSF-air-exchange for pharmacorefractory status epilepticus.

PMID- 16609808
TI  - Unusual MRI findings in primary central nervous system lymphoma presenting
      diffuse linear enhancements located in the perivascular space.

PMID- 16609809
TI  - Rapid improvement in cortical neuronal integrity in amyotrophic lateral sclerosis
      detected by proton magnetic resonance spectroscopic imaging.
AB  - Riluzole prolongs survival in amyotrophic lateral sclerosis. The temporal and
      spatial profile of its effect on the brain is unknown. We used proton magnetic
      resonance spectroscopic imaging to evaluate the neuronal response to 1 day of
      riluzole treatment in motor and non-motor regions of the brain. In 10 patients
      the N-acetylaspartate/total creatine (NAA/Cr) ratio increased in the precentral
      gyrus and supplementary motor area, but not in the post-central gyrus or parietal
      lobe. Improvement in cortical neuronal metabolic function in the motor cortex
      occurs early with riluzole treatment.

PMID- 16609810
TI  - Benign multiple sclerosis: cognitive, psychological and social aspects in a
      clinical cohort.
AB  - OBJECTIVES: A study of cognitive, psychological and social aspects in benign
      multiple sclerosis (MS). Methods One hundred and sixty three patients with benign
      MS (defined as disease duration > or = 15 years and Expanded Disability Status
      Scale (EDSS) score < or = 3.0 ) underwent neuropsychological testing on the Rao's
      Brief Repeatable Battery (BRB) and the Stroop test, evaluation of depression on
      the Montgomery and Asberg Depression Rating Scale (MADRS), of fatigue on the
      Fatigue Severity Scale (FSS) and of handicap on the Environmental Status Scale
      (ESS). Patients' cognitive performance was compared with that of 111
      demographically matched healthy controls. Cognitive impairment was defined as the
      failure in at least 3 tests, using the fifth percentile of controls' performance
      as the cut-off point. Clinical correlates of cognitive impairment were determined
      by multiple logistic regression analysis. RESULTS: Cognitive assessment led to
      the identification of 74 subjects (45%) with cognitive impairment. Significant
      fatigue was found in 80 subjects (49%) and depression in 88 patients (54%). In
      comparison with cognitively preserved subjects, cognitively impaired patients
      exhibited higher handicap scores on the ESS (p = 0.005). In the regression
      analysis, only EDSS scores were significantly associated with cognitive
      impairment (OR 1.8, 95%CI 1.2-2.6). CONCLUSION: Current definitions of benign MS
      may overestimate this entity, since they are mainly weighted for the patients'
      motor abilities and fail to capture relevant disease-related cognitive,
      psychological and social problems.

PMID- 16609811
TI  - Mitoxantrone versus cyclophosphamide in secondary-progressive multiple sclerosis:
      a comparative study.
AB  - Fifty secondary progressive multiple sclerosis (SPMS) patients who had lost one
      or more EDSS points in the prior two years were selected to receive either
      cyclophosphamide (25 patients, 13 females, 12 males, F/M = 1.08; mean age: 42.4
      years; mean disease duration: 13.3 years; mean EDSS at study entry: 5.7) or
      mitoxantrone (25 patients, 14 females, 11 males, F/M = 1.27; mean age: 38.2
      years; mean disease duration: 11.5 years; mean EDSS at study entry: 5.5). SPMS
      patients were treated for two years with clinical evaluation (relapse rate,
      disability progression) every three months and radiological imaging (conventional
      magnetic resonance imaging) before therapy initiation and at the end of the first
      and second years of therapy. Safety profile and costs of the two therapeutic
      protocols were also analysed. In terms of clinical and radiological measures the
      drugs exerted a quite identical effect on both, and produced a significant
      reduction in both relapse rate (mitoxantrone Mito): p = 0.001, cyclophosphamide
      (Cy): p = 0.003) and disability progression (Mito: p = 0.01; Cy: p = 0.01).
      Subgroups of mitoxantrone- and cyclophosphamide-responding patients were
      identified (14/25 and 17/25, respectively) and were characterized by a
      significantly shorter duration of the secondary progressive phase of the disease.
      In these subgroups, the improvement in the EDSS score at the end of therapy was
      highly significant (p<0.0001 for Mito, p = 0.0004 for Cy). The safety profiles of
      both drugs were acceptable; however, the Cy-based therapy protocol was
      significantly less expensive. We conclude that Cy should be considered as a
      therapeutic option in rapidly deteriorating SPMS patients.

PMID- 16609812
TI  - Cognition in the early stage of multiple sclerosis.
AB  - OBJECTIVE: Cognitive dysfunctions may contribute to limitation of everyday
      activities of patients with multiple sclerosis (MS). Recent studies have
      demonstrated that 45 to 65% of MS-patients are cognitively impaired. The profile
      of MS-related cognitive dysfunctions varies greatly. It includes memory and
      learning deficits, attention deficits, executive dysfunctions and visuo-spatial
      deficits. Most studies of cognition in MS examined patients in later stages,
      often including MS-patients with marked physical disabilities. Studies of
      cognitive dysfunctions in the early stage of the disease are rare. This study
      specifically aimed at evaluating and characterizing cognitive impairments in the
      early stage of MS, and determining specific patterns of cognitive dysfunction.
      METHODS: 21 MS patients, experiencing their first neurological symptoms not more
      than two years previously, and 22 healthy controls were compared. A comprehensive
      neuropsychological test-battery was used to evaluate MS-related cognition. The
      battery consisted of memory and learning tests, executive functioning tests and a
      visuo spatial functioning test. A computerized attention test-battery was also
      included, which assess accuracy and speed of test responses. In addition
      depression and intellectual capabilities were assessed. RESULTS: Compared with
      healthy controls, MS-patients in the early stage of the disease performed
      significantly lower on each neuropsychological assessment, except for verbal
      short-term memory. In particular, MS-patients showed a lengthened reaction time
      for simple and focused attention (19-38%), impaired non-verbal memory function
      (RVDLT recognition: 33%) and a planning deficit (24%). Associations between
      information processing speed and disease course and the employment situation were
      additionally found. However, patients did not have clinically relevant depression
      rates on the ADS-L and visuo spatial abilities remain preserved. CONCLUSION: Our
      findings revealed discrete cognitive dysfunction in MS-patients within the early
      stage of the disease.

PMID- 16609813
TI  - Cold adapted features of Vibrio salmonicida catalase: characterisation and
      comparison to the mesophilic counterpart from Proteus mirabilis.
AB  - The gene encoding catalase from the psychrophilic marine bacterium Vibrio
      salmonicida LFI1238 was identified, cloned and expressed in the catalase
      deficient Escherichia coli UM2. Recombinant catalase from V. salmonicida (VSC)
      was purified to apparent homogeneity as a tetramer with a molecular mass of 235
      kDa. VSC contained 67% heme b and 25% protoporphyrin IX. VSC was able to bind
      NADPH, react with cyanide and form compounds I and II as other monofunctional
      small subunit heme catalases. Amino acid sequence alignment of VSC and catalase
      from the mesophilic Proteus mirabilis (PMC) revealed 71% identity. As for cold
      adapted enzymes in general, VSC possessed a lower temperature optimum and higher
      catalytic efficiency (k (cat)/K (m)) compared to PMC. VSC have higher affinity
      for hydrogen peroxide (apparent K (m)) at all temperatures. For VSC the turnover
      rate (k (cat)) is slightly lower while the catalytic efficiency is slightly
      higher compared to PMC over the temperature range measured, except at 4 degrees
      C. Moreover, the catalytic efficiency of VSC and PMC is almost temperature
      independent, except at 4 degrees C where PMC has a twofold lower efficiency
      compared to VSC. This may indicate that VSC has evolved to maintain a high
      efficiency at low temperatures.

PMID- 16609814
TI  - Characterization of a beta-glycosidase from the thermoacidophilic bacterium
      Alicyclobacillus acidocaldarius.
AB  - In cell free extracts of the thermoacidophilic gram-positive bacterium
      Alicyclobacillus acidocaldarius ATCC27009, we have identified beta-gluco- and
      galactosidase activities showing a specific activity of 0.1 and 12 U/mg,
      respectively. The two enzymatic activities are associated with different
      polypeptides and we show here the functional cloning, the expression in
      Escherichia coli and the characterisation of the beta-glucosidase (Aabeta-gly).
      The enzyme, which is optimally active and stable at temperatures above 65 degrees
      C, belongs to glycoside hydrolase family 1 (GH1) and shows wide substrate
      specificity on different aryl-glycosides and cello-oligosaccharides with k
      (cat)/K (M) for 4-nitrophenyl-beta-D-glucoside and cellobiose of 2,976 and 185 s(
      1)mM(-1), respectively. Interestingly, upstream to the beta-glycosidase gene, we
      identified a second ORF homologous to the ATPase subunit of the bacterial ABC
      transporters (abc1) that is co-transcribed with the beta-glycosidase gene glyB
      and that could be involved in the carbohydrate import. The activity of the enzyme
      on cello-oligosaccharides of up to five glucose units strongly indicates that the
      enzyme could be involved in vivo in the degradation of glucans together with
      endoglucanase enzymes previously described. This, together with the co-expression
      of the two genes, suggests a role for the glyB-abc1 cluster in A. acidocaldarius
      in the degradation of cellulose and hemicelluloses.

PMID- 16609815
TI  - Replication of Heliothis virescens ascovirus in insect cell lines.
AB  - Ascoviruses (AVs) infect larvae of various insect pests belonging to the family
      Noctuidae. The result of AV infection in the hosts is cleavage of infected cells
      into vesicles, a unique feature of AV infection. Since insect cell lines
      facilitate the study of virus life cycles, attempts were made to analyze
      Heliothis virescens AV (HvAV3e) infection in several cell lines and compare cell
      pathology to larval infection. In this study, replication and cytopathological
      effects of HvAV3e on four different cell lines were investigated. HvAV3e
      replication was confirmed in three noctuid cell lines from Spodoptera frugiperda
      (Sf9) and Helicoverpa zea (BCIRL-Hz-AM1 and FB33). However, the virus did not
      replicate in the non-noctuid insect cell line from Pieris rapae (Pieridae).
      Despite replication of the virus in the three permissive cell lines, the
      cytopathological effects of the virus were significantly different from that of
      larval infection.

PMID- 16609816
TI  - Pns4 of rice dwarf virus is a phosphoprotein, is localized around the viroplasm
      matrix, and forms minitubules.
AB  - Rice dwarf virus (RDV), a member of the family Reoviridae, has a 12-segmented
      dsRNA genome. Seven segments, designated S1, S2, S3, S5, S7, S8, and S9, encode
      structural proteins, while the remainder encode nonstructural proteins. One of
      the nonstructural proteins, Pns4, which is encoded by S4, was characterized. Pns4
      was a phosphorylatable substrate in a phosphorylation assay in vivo; it
      associated with large cytoplasmic fibrils and formed novel minitubules in
      infected cultured cells of its leafhopper insect vector, as revealed by
      immunofluorescence and immunoelectron microscopy. Early in infection, Pns4 was
      detected at the periphery of the viroplasm, and it was then observed on amorphous
      or fibrillar inclusions, which were identified as bundles of minitubules, at
      later stages of infection. Since viroplasms are believed to be the site of RDV
      replication, the intracellular location of Pns4 suggests that this protein might
      be involved in the process of assembly of the RDV virion.

PMID- 16609817
TI  - Complete genome sequence of Daphne mosaic virus - a potyvirus from an ornamental
      shrub related to papaya leaf distortion mosaic virus.

PMID- 16609818
TI  - Preliminary results of a two-layered prosthetic repair for recurrent inguinal and
      ventral hernias combining open and laparoscopic techniques.
AB  - The use of prosthetic mesh has become the standard of care in the management of
      hernias because of its association with a low rate of recurrence. However,
      despite its use, recurrence rates of 1% have been reported in primary inguinal
      repair and rates as high as 15% with ventral hernia repair. When dealing with
      difficult recurrent hernias, the two-layer prosthetic repair technique is a good
      option. In the event of incarcerated or strangulated hernias, however; placement
      of prosthetic material is controversial due to the increased risk of infection.
      The same is true when hernia repairs are performed concurrently with potentially
      contaminated procedures such as cholecystectomy, appendectomy, or colectomy. The
      purpose of this study is to report our preliminary results on the treatment of
      recurrent hernias by combining laparoscopic and open techniques to construct a
      two-layered prosthetic repair using a four ply mesh of porcine small intestine
      submucosa (Surgisis, Cook Surgical, Bloomington, IN, USA) in a potentially
      infected field and a combination of polypropylene and ePTFE (Gore-Tex, W.L. Gore
      and Associates, Flagstaff, AZ, USA) in a clean field. From September 2002 to
      January 2004, nine patients (three males and six females) underwent laparoscopic
      and open placement of surgisis mesh in a two layered fashion for either recurrent
      incisional or inguinal hernias in a contaminated field. A total of eight
      recurrent hernia repairs were performed (five incisional, three inguinal) and one
      abdominal wall repair after resection of a metastatic tumor following open
      colectomy for colon carcinoma. Six procedures were performed in a potentially
      contaminated field (incarcerated or strangulated bowel within the hernia), two
      procedures were performed in a contaminated field because of infected
      polypropylene mesh, and one was in a clean field. Mean patient age was 56.4
      years. The average operating time was 156.8 min. Operative findings included
      seven incarcerated hernias (four incisional and three inguinal), one strangulated
      inguinal hernia, and one ventral defect after resection of an abdominal wall
      metastasis for a previous colon cancer resection. In two of the cases, there was
      an abscess of a previously placed polypropylene mesh. All procedures were
      completed with two layers of mesh (eight cases with surgisis and one with
      combination of polypropylene/ePTFE). Median follow up was 10 months.
      Complications included two seromas, one urinary tract infection, two cases of
      atelectasis and one prolonged ileus. There were no wound infections. The average
      postoperative length of stay was 7.8 days. There have been no mesh-related
      complications or recurrent hernias in our early postoperative follow-up period.
      The use of a new prosthetic device in infected or potentially infected fields,
      and the two-layered approach shows promising results. This is encouraging and
      provides an alternative approach for the management of difficult, recurrent
      hernias.

PMID- 16609819
TI  - Combined fascia and mesh repair of incisional hernias.
AB  - Incisional hernia is a relatively common complication following abdominal
      operations. Due to high recurrence rates following primary suture, a prosthetic
      mesh is now usually used to repair the hernia. Several different types of repair
      are described. A combined fascia and mesh technique avoids opening the peritoneal
      cavity and potential damage to bowel. This study describes results of this
      technique. Consecutive patients undergoing the operation were contacted to assess
      freedom from recurrence and satisfaction with results. Some 34 patients underwent
      36 incisional repairs. Of the 34 patients 21 were men and 13 were women with a
      median age of 69 years (range 31-86 years). The causative incisions were midline
      (30), Kochers (2), Pfannesteil (2) and transverse (2). The median time spent in
      hospital was three nights (range 1-14 days). Two patients developed seromas,
      another complained of pain soon after operation, one patient developed a
      superficial wound infection another developed a tender drain site which required
      exploration. One patient with significant co-morbidity died 13 days
      postoperatively from multiorgan failure. Freedom from recurrence of the hernia
      was 91% at 5 years. However patient survival was only 70% at 5 years. This
      technique is associated with low postoperative morbidity and a low recurrence
      rate. Patients presenting with incisional hernias have a poor long-term prognosis
      which needs to be borne in mind when planning intervention.

PMID- 16609820
TI  - Prospective clinical study of laparoscopic treatment of incisional and ventral
      hernia using a composite mesh: indications, complications and results.
AB  - The aim of this study is to establish the indications, safety, efficacy,
      feasibility and reproducibility of the laparoscopic technique in treating defects
      in the abdominal wall, including those of large dimensions, to standardise the
      surgical technique and to confirm the performance of the composite prosthesis
      used (Parietex, Sofradim). The study encompassed the period from January 2001 to
      December 2004 and included 178 nonselected patients (108 women and 70 men), with
      an average age of 56 years (range: 26-77 years) and an average body mass index
      (BMI) of 30 (range: 26-40). These patients were treated for either abdominal
      hernia (156 patients; 89.7%) or a primary defect (22 patients; 10.3%). The
      dimensions of the abdominal hernias treated varied from 4 to 26 cm (average: 12.1
      cm). All patients were treated using the laparoscopic technique, and all meshes
      were placed in the intraperitoneal position. Eleven (7%) postoperative
      complications arose after an average follow-up period of 29 months (range: 1-48
      months): seven seromas (4.4%) lasting for 4 weeks, with one becoming infected
      after being punctured repeatedly; we removed the infected prosthesis by
      laparoscopy; three (1.9%) patients with persistent neuralgia, which were resolved
      after 2 months with a prescription for FANS; one patient with a haematoma at the
      trocar site. There were also four recurrences (2.5%), all of which occurred
      between 1 and 3 months postsurgery: one in the 'small' group of abdominal hernias
      (less than 9 cm) and three in the 'large' group of abdominal hernias. With the
      exclusion of any primary defects, an adhesiolysis was carried out in 99.3% of the
      patients. In seven cases (4.4%) we carried out a raphe for speritonealisations of
      loops in the small intestine; in four patients (2.5%), following tenacious
      adhesion (one patient) and loops fixed to the previous scar by stitches (three
      patients), we carried out an intestinal perforation (ileus) which was sutured by
      laparoscopy. The average operating time was 65.6 min (range: 28-130 min), with an
      average postoperative period in the hospital of 2.1 days (range: 1-5 days). No
      conversion was observed, and mortality was zero. The results obtained during the
      clinical trial demonstrate the safety and efficacy of the laparoscopic technique
      and of the mesh used as well as the reproducibility of the technique in the
      intraperitoneal treatment of congenital and postincision defects in the abdominal
      wall, including those of large dimensions.

PMID- 16609821
TI  - Seronegative arthritis in patient with solitary bone plasmacytoma.
AB  - We report a patient with localized focus of the bone destruction due to a rare
      disease, solitary bone plasmacytoma (SBP). The patient suffered from arthritis,
      mimicking seronegative rheumatoid arthritis. To our knowledge, it is the first
      description of coexistence of arthritis and SBP.

PMID- 16609822
TI  - Educational issues in rheumatology. The musculoskeletal examination: a neglected
      skill.

PMID- 16609823
TI  - The burden of musculoskeletal disease--a global perspective.
AB  - Musculoskeletal diseases are one of the major causes of disability around the
      world and have been a significant reason for the development of the Bone and
      Joint Decade. Rheumatoid arthritis, osteoarthritis and back pain are important
      causes of disability-adjusted-life years in both the developed and developing
      world. COPCORD studies in over 17 countries around the world have identified back
      and knee pain as common in the community and are likely to increase with the
      ageing population. Musculoskeletal conditions are an enormous cost to the
      community in economic terms, and these figures emphasise how governments need to
      invest in the future and look at ways of reducing the burden of musculoskeletal
      diseases by encouraging exercise and obesity prevention campaigns.

PMID- 16609824
TI  - Persistence with weekly alendronate therapy among postmenopausal women.
AB  - INTRODUCTION: Although clinical trials indicate that oral bisphosphonates reduce
      osteoporotic fracture risk, compliance with bisphosphonate therapy in practice is
      suboptimal, with 1-year discontinuation rates exceeding 50%. METHODS: We
      conducted a retrospective cohort study among female members of a large integrated
      health care delivery system (Kaiser Permanente of Northern California), age 45
      years and older, to determine their persistence with weekly alendronate (defined
      as continuous use, allowing for a refill gap of 60 days), predictors of
      discontinuation, and subsequent osteoporosis therapy. We also examined the effect
      of varying the refill gap from 30 to 120 days on the discontinuation rate. From
      2002 through 2003, we identified 13,455 women (age 68.8+/-10.4 years) who
      initiated weekly oral alendronate therapy. RESULTS: Using a 60-day refill gap,
      the 1-year discontinuation rate was 49.6% [95% confidence interval (CI) 48.8
      50.4%]; this increased to 58.0% (CI 57.2-58.8%) with a 30-day gap and decreased
      to 42.2% (CI 41.1-43.0%) with a 120-day gap. Among those who discontinued
      therapy, about one-third restarted alendronate or another osteoporosis drug
      within 6 months. Baseline factors associated with alendronate discontinuation
      included prior bone mineral density testing [adjusted odds ratio (OR) 0.64, CI
      0.60-0.69], prior postmenopausal hormone therapy (OR 0.78, CI 0.73-0.84), prior
      high-dose oral glucocorticoid therapy (OR 1.26, CI 1.05-1.51), prior
      gastrointestinal diagnoses (OR 1.21, CI 1.09-1.36), and high number of
      therapeutic classes of prescriptions filled in the prior year (OR 1.21, CI 1.10
      1.32), although the final model had limited explanatory power. CONCLUSIONS: We
      conclude that apparent discontinuation rates are high within 1 year after
      treatment initiation, although a subset of women appears to restart
      bisphosphonate or other osteoporosis therapy. Because intermittent use and/or
      poor adherence is common, discontinuation rates based on data from administrative
      databases are sensitive to the refill gap length. In addition, we identified no
      clinical factors highly predictive of discontinuation.

PMID- 16609825
TI  - A new neurobehavioral model of autism in mice: pre- and postnatal exposure to
      sodium valproate.
AB  - Autism symptoms, including impairments in language development, social
      interactions, and motor skills, have been difficult to model in rodents. Since
      children exposed in utero to sodium valproate (VPA) demonstrate behavioral and
      neuroanatomical abnormalities similar to those seen in autism, the
      neurodevelopmental effects of this antiepileptic agent were examined in mice
      following its pre- or postnatal administration. Exposed pups were evaluated in a
      battery of neurodevelopmental procedures designed to assess VPA-induced
      retardation (wherein a behavior fails to mature on schedule), regression (wherein
      a behavior does mature on time but then deteriorates), or intrusions (wherein
      normal behaviors are overshadowed by stereotypic or self-injurious behaviors).
      The resulting observations were interpreted in the context of this new strategy
      to model autism.

PMID- 16609826
TI  - Motor signs distinguish children with high functioning autism and Asperger's
      syndrome from controls.
AB  - While many studies of motor control in autism have focused on specific motor
      signs, there has been a lack of research examining the complete range of subtle
      neuromotor signs. This study compared performance on a neurologic examination
      standardized for children (PANESS, Physical and Neurological Exam for Subtle
      Signs, Denckla [1974 Developmental Medicine and Child Neurology, 16(6), 729-741])
      between a group of 40 boys aged 6-17 with autism and average range IQs and a
      group of 55 typically developing boys. The Autism group was shown to have
      significant impairment on several measures of motor control compared to the
      Control group. Regression analyses revealed that a model including four PANESS
      variables offered a high level of discrimination in distinguishing boys with high
      functioning autism from controls.

PMID- 16609827
TI  - An MRI study of minor physical anomalies in autism.
AB  - The objective of this investigation was to examine the existence of minor
      physical anomalies (MPA) in autism. The interorbital and interlens distances were
      measured on MRI scans obtained from a sample of 40 non-mentally retarded
      individuals with autism and 41 healthy controls. No differences were observed
      between the two groups on any measurements. However, when the analysis was
      conducted using a split median procedure, individuals with autism and either low
      FSIQ, PIQ, or VIQ had shorter interorbital distances when compared to controls.
      Hypotelorism is a MPA that may be present in a subgroup of individuals with
      autism. Additional research is warranted using large sample sizes with a wide
      range of intellectual functioning.

PMID- 16609828
TI  - Association of violence victimization with inconsistent condom use in HIV
      infected persons.
AB  - The association of violence victimization with current condom use in HIV-infected
      persons was examined in this cross-sectional study. The HIV-Alcohol Longitudinal
      Cohort (HIV-ALC) recruited HIV-infected participants with a history of alcohol
      problems. Interviews assessed violence histories and current sexual behaviors. Of
      the 349 participants (79% men), 38% reported inconsistent condom use and 80%
      reported a violence history. Lifetime sexual violence was reported by 40% and
      lifetime physical violence (without sexual violence) by 40%. Participants
      reporting lifetime sexual violence had greater odds of inconsistent condom use
      than participants without any history of violence. A history of childhood sexual
      violence was also associated with greater odds of inconsistent condom use than
      participants without a history of childhood sexual violence. A history of sexual
      violence may in part explain HIV-infected persons' greater risk for transmitting
      HIV through high-risk sexual behaviors.

PMID- 16609830
TI  - Effects of cyclosporin a on neurological outcome and serum biomarkers in the same
      setting of spinal cord ischemia model.
AB  - Spinal cord ischemic injury is one of the feared complications during aortic
      cross-clamping. The aim of this study was to investigate whether cyclosporin A
      (CsA) has a protective effect on spinal cord during ischemia in a rabbit model. A
      total of 22 New Zealand white rabbits were studied in three groups. One of the
      groups served as a sham group (n=7), in which only laparatomy was performed and
      closed. One group served as a control group (n=7), in which rabbits had their
      abdominal aortas cross-clamped for 40 min following median laparatomy. The last
      group was the CsA group (n=8), in which rabbits underwent the same procedure as
      the control group as well as CsA infusion at 20 mg/(kg . hr) over 60 min starting
      with aortic cross-clamping and continuing in the first 20 min of reperfusion.
      Neurological outcome of rabbits was evaluated according to Johnson's scale at
      postoperative hours 24 and 48 in all groups, and then they were killed. Their
      spinal cords were harvested, and segments corresponding to L4-L6 were prepared
      for pathological examination. Serum neuron-specific enolase (NSE) and nitric
      oxide (NO) levels were measured prior to and following aortic occlusion, and
      comparisons were made. Physiological data were similar in all groups. Rabbits in
      the sham group did not have any neurological deficit. However, all rabbits in the
      control group showed severe neurological deficits, including total paraplegia in
      five. According to Johnson's scale, neurological status of the rabbits at
      postoperative hour 48 was better in the CsA group compared to controls (p<0.01).
      Pathological examination of spinal cord specimens revealed a higher viability
      index in the CsA group compared to controls (p<0.01). Serum NSE and NO levels
      were lower in CsA-treated animals compared to controls. Our results demonstrate
      that CsA, when administered during ischemia and in the early period of
      reperfusion, may reduce neuronal damage in the spinal cord in a rabbit model of
      transient spinal cord ischemia.

PMID- 16609829
TI  - Venous ulcer fibroblasts respond to basic fibroblast growth factor at the cell
      cycle protein level.
AB  - Fibroblasts cultured from venous ulcers demonstrate phenotypic characteristics of
      cellular senescence including slow growth, altered morphology, upregulation of
      fibronectin, and increased senescence-associated beta-galactosidase activity. In
      senescent cells, arrest of cell replication is related to overexpression of p21
      and underexpression of phosphorylated tumor-suppressor protein retinoblastoma
      (ppRb). The regulatory mechanisms for cell proliferation in venous ulcer
      fibroblasts are unknown. In this study, venous ulcer fibroblasts are examined for
      cell cycle protein expression and modulation by basic fibroblast growth factor
      (bFGF). Fibroblasts were isolated from the venous ulcer of the distal lower
      extremity (fb-D) of patients with chronic venous insufficiency. A control biopsy
      was obtained from the proximal ipsilateral thigh (fb-P). Paired cultures were
      plated at 100,000 cells/plate and the cells synchronized. After 24 hr, one
      culture set was treated with bFGF (20 ng/mL) and the other was kept in culture
      medium only (untreated). All cultures, treated and untreated, were lysed
      following 24 hr of incubation, and the lysate was used to perform immunoblot
      analysis for p21, ppRb, and cyclin D1. Immunoblot samples were standardized to
      protein content. In all patients analyzed (n = 4), at basal levels (untreated) fb
      D demonstrated significant overexpression of p21 versus fb-P (p = 0.016).
      Treatment with bFGF resulted in significant downregulation of p21 levels for fb-D
      (p = 0.008) and fb-P (p = 0.037) compared to untreated fibroblasts. ppRb was
      underexpressed in fb-D versus fb-P (p = 0.069). Treatment with bFGF increased
      ppRb significantly in fb-D (p = 0.030) and in fb-P (p = 0.027) compared to
      untreated fibroblasts. No differences were observed in cyclin D1 with respect to
      basal levels in fb-P versus fb-D or in treated versus untreated groups. Venous
      ulcer fibroblasts show phenotypic similarity to senescent cells, with
      overexpression of p21 as well as down regulation of phosphorylated pRb. The
      aberrations seen in the cell cycle proteins in fb-D are similar to those seen in
      senescent cells; however, bFGF can modulate important cell cycle regulatory
      proteins, promoting a proliferative environment in fb-D that is not possible in a
      senescent cell. The role of bFGF may be useful in the clinical treatment of
      venous ulcer pathology.

PMID- 16609831
TI  - Different endovascular referral patterns are being learned in medical and
      surgical residency training programs.
AB  - Physicians in residency training will be the referring physicians of tomorrow. We
      sought to determine the current surgical and medical trainees' perception of
      vascular surgery's endovascular qualifications and capabilities. An anonymous
      survey was sent to all general surgery and internal medicine residents at a
      single academic institution. Respondents answered the question "Which specialty
      is the most qualified to perform (1) inferior vena cava (IVC) filter insertion;
      (2) angiograms, angioplasty, and stenting of the carotid arteries; (3) renal
      arteries; (4) aorta; and (5) lower extremity arteries?" For each question,
      respondents chose one response, either vascular surgery, interventional
      radiology, interventional cardiology, or do not know. One hundred respondents
      completed the survey (general surgery, n=50; internal medicine, n=50). There was
      a significant difference in the attitudes of surgery and medicine residents when
      choosing the most qualified endovascular specialist (p<0.05). Surgery residents
      chose vascular surgery as the most qualified specialty for each listed procedure:
      carotid (80%, n=40), IVC (56%, n=28), aorta (100%, n=50), extremity (86%, n=43),
      renal (78%, n=39). Medicine residents chose vascular surgery as the most
      qualified specialty less frequently: carotid (66%, n=33), IVC (6%, n=3), aorta
      (88%, n=44), extremity (72%, n=36), renal (16%, n=8). There was no significant
      difference in specialty selection based on postgraduate year. There is a large
      discrepancy between surgical and medical trainees' perception of vascular
      surgery's endovascular abilities, particularly regarding IVC placement and renal
      artery interventions. If our own institution mirrors the nation, each passing
      year a significant portion of the 21,722 graduating internal medicine residents
      go into practice viewing vascular surgeons as second-tier endovascular providers.
      A concerted campaign should be undertaken to educate medical residents regarding
      the skills and capabilities of vascular surgeons.

PMID- 16609832
TI  - Total videoscopic iliac artery aneurysm repair.
AB  - We report a case of totally videoscopic iliofemoral bypass to treat an isolated
      iliac artery aneurysm. Both iliac and femoral approaches and anastomoses were
      performed under videoscopic control. This intervention allowed us to obtain the
      well-known long term results of conventional iliac artery aneurysm repair while
      reducing operative trauma.

PMID- 16609833
TI  - Late infection of an endovascular stent graft with septic embolization, colonic
      perforation, and aortoduodenal fistula.
AB  - We report on a 52-year-old male who developed late stent graft infection
      resulting in infective aneurysm formation with systemic septic embolization and
      aortoduodenal fistulation 9 months following endoluminal repair of an abdominal
      aortic aneurysm. Although endoluminal stent graft infection and erosion into
      surrounding viscera is rare, we highlight the need for awareness of this
      potentially catastrophic complication.

PMID- 16609834
TI  - 1H, 13C and 15N resonance assignments for the reduced forms of thioredoxin 1 and
      2 from S. cerevisiae.

PMID- 16609835
TI  - 1H and 15N resonance assignment of the first module of FGFR1.

PMID- 16609836
TI  - 1H, 15N, and 13C resonance assignment of the C2A domain of rabphilin 3A.

PMID- 16609839
TI  - [Spondylitis/spondylodiscitis].
AB  - Spondylitis is an inflammation of the vertebral body. If the infection is
      manifested in the vertebral motor segment it is called spondylodiscitis, which
      can be divided into specific and nonspecific forms. It is clinically impressive
      that at the beginning of the disease, the patients who are quite often
      immunosuppressed suffer from localized, especially nocturnally exacerbated
      backache. The initial diagnostic work-up generally consists of clinical history,
      examination, laboratory tests, and (especially advanced) imaging findings.
      Although computed tomography still remains the most frequently used advanced
      imaging technique, magnetic resonance imaging is the golden standard for the
      diagnosis of spondylitis and spondylodiscitis.

PMID- 16609840
TI  - Validation and use of three complementary analytical methods (LC-FLS, LC-MS/MS
      and ICP-MS) to evaluate the pharmacokinetics, biodistribution and stability of
      motexafin gadolinium in plasma and tissues.
AB  - Liquid chromatography-fluorescence (LC-FLS), liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and inductively coupled plasma-mass spectrometry (ICP-MS)
      methods were developed and validated for the evaluation of motexafin gadolinium
      (MGd, Xcytrin) pharmacokinetics and biodistribution in plasma and tissues. The LC
      FLS method exhibited the greatest sensitivity (0.0057 microg mL(-1)), and was
      used for pharmacokinetic, biodistribution, and protein binding studies with small
      sample sizes or low MGd concentrations. The LC-MS/MS method, which exhibited a
      short run time and excellent selectivity, was used for routine clinical plasma
      sample analysis. The ICP-MS method, which measured total Gd, was used in
      conjunction with LC methods to assess MGd stability in plasma. All three methods
      were validated using human plasma. The LC-FLS method was also validated using
      plasma, liver and kidneys from mice and rats. All three methods were shown to be
      accurate, precise and robust for each matrix validated. For three mice, the mean
      (standard deviation) concentration of MGd in plasma/tissues taken 5 hr after
      dosing with 23 mg kg(-1) MGd was determined by LC-FLS as follows: plasma (0.025+/
      0.002 microg mL(-1)), liver (2.89+/-0.45 microg g(-1)), and kidney (6.09+/-1.05
      microg g(-1)). Plasma samples from a subset of patients with brain metastases
      from extracranial tumors were analyzed using both LC-MS/MS and ICP-MS methods.
      For a representative patient, > or = 90% of the total Gd in plasma was accounted
      for as MGd over the first hour post dosing. By 24 hr post dosing, 63% of total Gd
      was accounted for as MGd, indicating some metabolism of MGd.

PMID- 16609837
TI  - Lactacystin exhibits potent anti-tumor activity in an animal model of malignant
      glioma when administered via controlled-release polymers.
AB  - Lactacystin, a proteasome-inhibitor, has been shown to induce apoptosis of
      experimental gliomas in vitro. However, its systemic toxicity prevents further
      clinical use. To circumvent this problem, lactacystin can be delivered
      intratumorally. We tested the efficacy of lactacystin incorporated into
      controlled-release polymers for treating experimental gliomas. 9L-gliosarcoma and
      F98-glioma cell lines were treated with lactacystin (10-100 microg/ml) for 72 h
      in vitro. Cell-viability was measured with MTT-assays. Toxicity of
      lactacystin/polycarboxyphenoxypropane-sebacic-acid (pCPP : SA) polymers was
      tested in vivo using Fischer-344 rats intracranially implanted with lactacystin
      polymers loaded from 0.1 to 2% lactacystin by weight. The efficacy of 1, 1.3, 1.5
      and 1.7% lactacystin/pCPP : SA polymers was determined in Fischer-344 rats
      intracranially challenged with 9L and treated either simultaneously or 5 days
      after tumor implantation. Lactacystin was cytotoxic in 9L cells, causing a 16 +/-
      8% growth inhibition at 10-microg/ml that increased to 78 +/- 4% at 100
      microg/ml. Similarly, lactacystin inhibited growth of F98 by 18 +/- 8% at 10
      microg/ml and 74 +/- 2% at 100-microg/ml in vitro. Polymers released lactacystin
      for 21 days and intracranial implantation in rats neither generate local nor
      systemic toxicity at doses lower than 2%. Treatment with lactacystin/pCPP : SA
      polymers with loading concentrations of 1.0, 1.3, and 1.5% prolonged survival of
      animals intracranially challenged with 9L when polymers where inserted in the day
      of tumor implantation. In conclusion, lactacystin exhibits potent cytotoxic
      activity against 9L and F98 in vitro, it can be efficiently incorporated and
      delivered using controlled-release polymers, and at the proposed concentrations
      lactacystin polymers are safe for CNS delivery and prolong survival in the 9L
      model.

PMID- 16609841
TI  - Simultaneous analysis of cationic, anionic, and neutral compounds using
      monolithic CEC columns.
AB  - A new capillary electrochromatography (CEC) column for the simultaneous analysis
      of cationic, neutral, and anionic compounds using CEC-ESI-MS is described. Three
      different silica monolith columns were prepared by changing the poly(ethylene
      glycol) (PEG) contents for comparison of the separation property of these
      columns. Different separation programs were used for the simultaneous separation
      of different charged compounds under the same conditions. The column prepared
      with 80 mg of PEG separated typical compounds within 15 min using 1 M formic acid
      as the electrolyte. The analytes migrated in the order of cationic, neutral, and
      anionic compounds, which means that the migration order was mainly determined by
      the electrophoresis. The hydrodynamic flow by pressure from the inlet side was
      significant for a stable analysis to be achieved. The effect of the composition
      of the sheath liquid was also examined. All analytes (14 amino acids, thiourea,
      urea, citric acid, and ATP) were detectable when 1% acetic acid in 50% (v/v)
      methanol was used as the sheath liquid.

PMID- 16609842
TI  - Comparisons between LIBS and ICP/OES.
AB  - In the framework of the development of new techniques, the ability of laser
      induced breakdown spectroscopy (LIBS) to analyse remotely complex aqueous
      solutions was investigated. The jet configuration with a collimated gas stream
      was chosen because it appeared to be the most promising method for the LIBS
      probe, particularly in terms of sensitivity and repeatability. For emission
      collection, the echelle spectrometer offers a simultaneously recorded wavelength
      range from the UV to the near IR and is interesting for multielemental analysis
      for LIBS and also for inductively coupled plasma (ICP) optical emission
      spectroscopy (OES). The importance of parameters influencing the quantitative
      results of LIBS such as multispecies analysis, sheath gas, use of an internal
      standard and temporal parameters for analysis is described. LIBS quantitative
      data have been directly compared with results from the more standard ICP/OES
      technique.

PMID- 16609843
TI  - Procedure for increasing the detection responses of estrogens in LC-MS based on
      introduction of a nitrobenzene moiety followed by electron capture atmospheric
      pressure chemical ionization.
AB  - A practical procedure for determining estrogens in biological fluids has been
      studied using liquid chromatography-electron capture atmospheric pressure
      chemical ionization-mass spectrometry combined with derivatization. Among the
      commercially available reagents (4-nitrobenzoyl chloride, 2,4
      dinitrofluorobenzene, 4-nitrobenzenesulfonyl chloride and 4-nitrobenzyl bromide),
      4-nitrobenzenesulfonyl chloride was of the most practical use; it rapidly and
      quantitatively reacted with estrogens and increased the detection responses by 8
      23 times. The derivatization method allowed the reproducible and accurate
      quantification of serum and urine estrone and estradiol of a pregnant woman,
      which is useful for diagnosis of the fetoplacental function, with small amounts
      (10 mul) of sample and a simple pretreatment procedure. Tatsuya Higashiis
      Associate Professor of the Laboratory of Clinical Analytical Sciences (Professor
      Kazutake Shimada's research group) at the Graduate School of Natural Science and
      Technology of Kanazawa University. He received the Japan Society for Analytical
      Chemistry Award for Young Scientists in 2003 and the Pharmaceutical Society of
      Japan Award for Young Scientists in 2006. His current research interests are the
      development of methods for increasing sensitivity in LC-MS to detect and
      characterize trace amounts of biologically active steroids, such as estrogens,
      androgens and neuroactive steroids.

PMID- 16609844
TI  - Recent advances in fluorescent probes for the detection of reactive oxygen
      species.
AB  - Reactive oxygen species (ROS) have captured the interest of many researchers in
      the chemical, biological, and medical fields since they are thought to be
      associated with various pathological conditions. Fluorescent probes for the
      detection of ROS are promising tools with which to enhance our understanding of
      the physiological roles of ROS, because they provide spatial and temporal
      information about target biomolecules in in vivo cellular systems. ROS probes,
      designed to detect specific ROS with a high selectivity, would be desirable,
      since it is now becoming clear that each ROS has its own unique physiological
      activity. However, dihydro-compounds such as 2',7'-dichlorodihydrofluorescein
      (DCFH), which have traditionally been used for detecting ROS, tend to react with
      a wide variety of ROS and are not completely photostable. Some attractive
      fluorescent probes that exhibit a high degree of selectivity toward specific ROS
      have recently been reported, and these selective probes are expected to have
      great potential for elucidating unknown physiological mechanisms associated with
      their target ROS. This review focuses on the design, detection mechanism, and
      performance of fluorescent probes for the detection of singlet oxygen ((1)O(2)),
      hydrogen peroxide (H(2)O(2)), hydroxyl radicals ((.)OH), or superoxide anion
      (O(2) (-.)), a field in which remarkable progress has been achieved in the last
      few years.

PMID- 16609845
TI  - Optical technologies for the read out and quality control of DNA and protein
      microarrays.
AB  - Microarray formats have become an important tool for parallel (or multiplexed)
      monitoring of biomolecular interactions. Surface-immobilized probes like
      oligonucleotides, cDNA, proteins, or antibodies can be used for the screening of
      their complementary targets, covering different applications like gene or protein
      expression profiling, analysis of point mutations, or immunodiagnostics. Numerous
      reviews have appeared on this topic in recent years, documenting the intriguing
      progress of these miniaturized assay formats. Most of them highlight all aspects
      of microarray preparation, surface chemistry, and patterning, and try to give a
      systematic survey of the different kinds of applications of this new technique.
      This review places the emphasis on optical technologies for microarray analysis.
      As the fluorescent read out of microarrays is dominating the field, this topic
      will be the focus of the review. Basic principles of labeling and signal
      amplification techniques will be introduced. Recent developments in total
      internal reflection fluorescence, resonance energy transfer assays, and time
      resolved imaging are addressed, as well as non-fluorescent imaging methods.
      Finally, some label-free detection modes are discussed, such as surface plasmon
      microscopy or ellipsometry, since these are particularly interesting for
      microarray development and quality control purposes.

PMID- 16609846
TI  - Axial oblique MR imaging of the intrinsic ligaments of the wrist: initial
      experience.
AB  - OBJECTIVE: To evaluate two separate MR sequences acquired in the axial oblique
      plane, parallel to the long axis of the scapholunate (SL) and lunotriquetral (LT)
      ligaments, to determine whether the addition of these sequences to the standard
      MR wrist examination improves visualization of the intrinsic ligaments, and the
      evaluation of their integrity. To our knowledge, this plane has not been
      described in the literature previously. DESIGN AND PATIENTS: In total we
      evaluated 26 patients with chronic wrist pain or instability, referred for MR
      imaging following assessment by an orthopedic surgeon or physiatrist. All
      patients underwent initial conventional tri-compartment wrist arthrography, which
      served as the reference standard. This was immediately followed by MR
      arthrography, in the standard coronal and true axial planes, as well as in the
      axial oblique plane. The SL and LT ligaments were initially assessed for the
      presence or absence of tear, using the standard coronal and true axial sequences,
      and subsequently re-evaluated with the addition of the axial oblique planes.
      RESULTS: A total of ten intrinsic ligament tears were identified with
      conventional arthrography: six SL and four LT tears. Five of the six SL tears
      were identified on the standard sequences. All six were diagnosed with the
      addition of the oblique sequences. There were three false-positive SL tears
      identified using standard MR imaging, and two false-positives with the addition
      of the oblique sequences. No LT tear was identified on standard sequences,
      whereas all four were confidently seen with the addition of oblique images. No
      false-positives of the LT ligament were recorded with either standard or axial
      oblique sequences. CONCLUSION: The study suggests that the addition of axial
      oblique MR sequences helps identify tears to the intrinsic ligaments of the
      wrist, particularly the LT ligament. In addition, the axial oblique images assist
      in localization of the tear.

PMID- 16609847
TI  - Multifocal PVNS in a child--followed over 25 years.
AB  - Pigmented villonodular synovitis (PVNS) is a rare disorder of unknown aetiology,
      characterised by a destructive fibrohistiocytic proliferation with production of
      villous and nodular protrusions. The disease is commonly monoarticular, and
      involves the knee in 80% of cases. Occurrence in a child and involvement of
      multiple joints are extremely unusual. We present a case of multiple joint PVNS
      in a patient who first presented at the age of five and was subsequently followed
      up for over twenty-five years. The literature on the subject is briefly reviewed.

PMID- 16609848
TI  - Expression of the actin stress fiber-associated protein CLP36 in the human
      placenta.
AB  - Differentiation processes in the trophoblast comprise polarization, cell fusion
      and migration. All these processes involve dramatic reorganizations of
      cytoskeletal proteins such as intermediate filaments or actin. Due to very
      restricted knowledge on cytoskeletal changes in trophoblast, we analyzed the
      protein expression of an actin stress fiber-associated protein, the carboxy
      terminal LIM domain protein (CLP36). CLP36 belongs to the enigma family of
      proteins, binds to alpha-actinin and is involved in the cytoskeletal
      reorganization and signal transduction of a variety of cells. CLP36 protein was
      found to be exclusively expressed in the cytotrophoblast layer. Colocalization of
      CLP36 with Mib-1 revealed that CLP36 protein expression is restricted to
      proliferative and early post-proliferative trophoblast cells. Blockage of
      syncytial fusion by culture of villous explants in the presence of caspase 8
      inhibitors further supported this notion since CLP36 was only found in the basal
      and proliferative layer of the multilayered cytotrophoblast. We present evidence
      for the exclusive protein expression of CLP36 in proliferative and early post
      proliferative trophoblast cells. Pathological pregnancy syndromes such as
      preeclampsia are driven by alterations of trophoblast differentiation and
      turnover, where it needs to be elucidated whether CLP36 is involved in these
      alterations.

PMID- 16609849
TI  - Bilateral atypical choroid plexus papillomas in cerebellopontine angles mimicking
      neurofibromatosis 2.

PMID- 16609851
TI  - Characterization of tau pathologies in gray and white matter of Guam parkinsonism
      dementia complex.
AB  - Guam parkinsonism-dementia complex (PDC) is a neurodegenerative tauopathy in
      ethnic Chamorro residents of the Mariana Islands that manifests clinically with
      parkinsonism as well as dementia and is characterized neuropathologically by
      prominent cortical neuron loss in association with extensive telencephalic
      neurofibrillary tau pathology. To further characterize cortical gray and white
      matter tau, alpha-synuclein and lipid peroxidation pathologies in Guam PDC, we
      examined the brains of 17 Chamorro PDC and control subjects using biochemical and
      immunohistological techniques. We observed insoluble tau pathology in both gray
      and white matter of PDC and Guam control cases, with frontal and temporal lobes
      being most severely affected. Using phosphorylation dependent anti-tau
      antibodies, abundant tau inclusions were detected by immunohistochemistry in both
      neuronal and glial cells of the neocortex, while less alpha-synuclein pathology
      was observed in more limited brain regions. Further, in sharp contrast to
      Alzheimer's disease (AD), levels of the lipid peroxidation product 8, 12-iso
      iPF(2alpha)-VI isoprostane were not elevated in Guam PDC brains relative to
      controls. Thus, although the tau pathologies of Guam PDC share similarities with
      AD, the composite Guam PDC neuropathology profile of tau, alpha-synuclein and 8,
      12-iso-iPF(2alpha)-VI isoprostane reported here more closely resembles that seen
      in other tauopathies including frontotemporal dementias (FTDs), which may imply
      that Guam PDC and FTD tauopathies share underlying mechanisms of
      neurodegeneration.

PMID- 16609850
TI  - Progressive dopaminergic neurodegeneration of substantia nigra in the zitter
      mutant rat.
AB  - Zitter mutant rats exhibit abnormal metabolism of superoxide species and
      demonstrate progressive degeneration of dopamine (DA) neurons in the substantia
      nigra (SN). Furthermore, long-term intake of vitamin E, an effective free radical
      scavenger, prevents the loss of DA neurons caused by free radicals. However, it
      is unclear how this degeneration progresses. In this study, we ultrastructurally
      examined cell death in the zitter mutant rat SN. Conventional electron
      microscopic examination revealed two different types of neurons in the SN pars
      compacta. In zitter mutant rats, although the first type (clear neurons)
      exhibited no obvious ultrastructural changes with aging, the second type (dark
      neurons) demonstrated age-related damage from 2 months. Immunoelectron
      microscopic analysis clarified that the second-type neurons were dopaminergic
      neurons. In the dopaminergic neuronal somata, many lipofuscin granules and
      abnormal endoplasmic reticula were observed from 2 months of age, and these
      dopaminergic neurons showed progressive degeneration with age. Moreover, in
      zitter mutant rats, abnormally enlarged myelinated axons with dense bodies and
      splitting myelin with dense material were observed in the SN at 2, 4, and 12
      months, and oligodendrocytes with numerous lipofuscin, multivesicular bodies,
      multilamellar bodies, and dense bodies were frequently observed at 4 and 12
      months. These findings clarified that dopaminergic neurons in zitter mutant rats
      had degenerated with age, and that myelinated axons also exhibited age-related
      injury. Moreover, ubiquitin-immunohistochemical analysis indicated that the
      accumulation of products of the endosomal-lysosomal system may be involved in
      this degeneration.

PMID- 16609852
TI  - Pathological heterogeneity of the precentral gyrus in Pick's disease: a study of
      16 autopsy cases.
AB  - This report concerns the upper motor neuron involvement in 16 autopsy cases of
      Pick disease with Pick bodies, including 11 cases reported by us previously.
      Prominent, circumscribed atrophy of the precentral gyrus, conspicuously in the
      lower portion, was noted in one case. Loss of Betz cells and astrocytosis of the
      precentral gyrus layer V were encountered in 15 cases (94%) and eight cases
      (50%), respectively. Appearance of Pick bodies and ballooned neurons in the
      precentral gyrus layer V was confirmed in seven cases (44%). Degeneration of the
      pyramidal tract in the medulla oblongata was noted in all 15 cases in which this
      structure was examined. Pyramidal signs were observed in four (67%) of the six
      cases that were neurologically sufficiently examined: hyperreflexia in four cases
      (67%), spasticity in one case (17%). Babinski sign was not encountered in any of
      the six cases. In all four cases having pyramidal signs, degeneration of the
      pyramidal tract was observed. In contrast, two cases having degeneration of the
      pyramidal tract did not develop pyramidal signs. In Pick's disease with Pick
      bodies, obvious involvement of the precentral gyrus and pyramidal tract was not
      previously noticed. Furthermore, we suggest that pyramidal signs in Pick's
      disease with Pick bodies have been underestimated.

PMID- 16609853
TI  - Structural diversity and functional novelty of new carotenoid biosynthesis genes.
AB  - Many new carotenoid synthesis genes have recently been identified through genomic
      sequencing or functional cloning. Some of them exhibit novel structures and/or
      novel functions. This review describes such examples in the families of lycopene
      beta-cyclases, putative homologues of phytoene dehydrogenases and new carotenoid
      hydroxylases. Both the functionally novel lycopene beta-monocyclases and
      structurally novel fusion-type of lycopene beta-cyclases were described. Another
      newly discovered sequence of lycopene beta-cyclase described might represent a
      new class of lycopene beta-cyclases previously not identified in several
      cyanobacteria. Three examples of putative homologues of phytoene dehydrogenases
      were described, however, they were confirmed to encode different and/or new
      functions such as beta-carotene ketolase, 4,4'-diapolycopene oxygenase or
      prolycopene isomerase. Two new carotenoid hydroxylase genes were described that
      encoded the new function of 2,2'-beta-ionone ring hydroxylase or 3,3'
      isorenieratene hydroxylase. Phylogenetic analysis of these genes shed light on
      their possible evolutionary origins. These new genes also provide tools for
      synthesis of novel and desirable carotenoids by genetic engineering.

PMID- 16609854
TI  - Comparative antibacterial potential of selected aldehyde-based biocides and
      surfactants against planktonic Pseudomonas fluorescens.
AB  - The antimicrobial efficacy of two aldehyde-based biocides (glutaraldehyde, GTA,
      and ortho-phthalaldehyde, OPA) and two surfactants (cetyltrimethyl ammonium
      bromide, CTAB, and sodium dodecyl sulphate, SDS) was tested against planktonic
      Pseudomonas fluorescens. The antimicrobial effects were evaluated by respiratory
      activity as a measure of the oxygen uptake rate, adenosine triphosphate (ATP)
      release, outer membrane proteins (OMP) expression and cellular colour changes.
      The results were compared with the bacterial characteristics without chemical
      treatment. Tests in the presence of bovine serum albumin (BSA), in order to mimic
      a disinfection process in the real situation under dirty conditions, were
      performed according to the European Standard EN-1276. P. fluorescens was
      completely inactivated with OPA (minimum bactericidal concentration, MBC = 0.5
      mM) and CTAB (MBC = 5 mM) and was resistant to GTA and SDS. Only CTAB promoted
      cellular disruption and consequent ATP release. The antimicrobial action of the
      chemicals tested was significantly reduced when BSA was introduced into the
      bacterial cultures, increasing markedly the MBC values. Additionally, the
      presence of BSA acted as a disruption protective agent when CTAB was applied and
      stimulated the bacterial respiratory activity when lower concentrations of SDS
      were tested. The OMP of the bacterial cells was affected by the application of
      both surfactants. OMP expression remained unaltered after biocide treatment.
      Bacterial colour change was noticed after treatment with biocides and
      surfactants. In summary, P. fluorescens was extremely resistant to GTA and SDS,
      with antimicrobial action being quenched markedly by the reaction with BSA.

PMID- 16609855
TI  - Preliminary report on the biological effects of space flight on the producing
      strain of a new immunosuppressant, Kanglemycin C.
AB  - Kanglemycin C (K-C) is a new immunosuppressant isolated from the culture broth of
      Nocardia mediterranei var. kanglensis 1747-64. To improve the productivity of K-C
      and to study the biological effects of space flight on its producing strain,
      spores from five K-C producing strains (U-10, U-15, U-7, M-13, gamma-33) mutated
      from the wild strain N. mediterranei var. kanglensis 1747-64 were carried into
      space by an unmanned spaceship, "Shenzhou III" (Divine Vessel III) on March 25,
      2002. Comparatively, the strain U-7 was the highest K-C producing strain among
      the above five starting strains when cultivated in 500-ml Erlenmeyer flasks.
      After a 6 day and 18 h flight, the treated spores went through serial screening
      processes to screen for high-yield K-C mutant strains, using thin layer
      chromatography and high performance liquid chromatography (HPLC). The K-C yield
      produced by one mutant strain, designated as F-16, derived from the starting
      strain U-7 was increased by up to 200% when compared to that produced by the
      starting strain U-7 in 500-ml Erlenmeyer flasks after careful postflight HPLC
      analysis. Another mutant strain, designated as F-210, derived from the starting
      strain M-13 showed reduced productivity of K-C as well as exhibited changes in
      some morphological and physiological characteristics. For example, the broth
      color of the strain F-210 changed from yellow to purple after 96 h of culture,
      but that of the ground control strain M-13 remained yellow. Similarly, the
      mycelium morphological change from filamentous to coccoid of F-210 occurred later
      than that of ground control M-13. Examination of the survivability of postflight
      spores indicated that exposure to radiation, during the 162 h of space flight,
      plays a critical role in the survival rates of spores such that spores exposed to
      strong radiation exhibited lower survival rates than spores exposed to weak
      radiation.

PMID- 16609857
TI  - Health-related quality of life in patients with adolescent idiopathic scoliosis
      after treatment: short-term effects after brace or surgical treatment.
AB  - For treatment of teenagers with progressive adolescent idiopathic scoliosis in an
      early stage, two options are generally considered: treatment with a brace or
      observation followed by surgery if necessary. Many doctors and patients prefer
      conservative treatment (i.e. brace treatment) to surgical treatment, because
      surgery of the spine is generally considered a drastic intervention. Because
      potential differences in health-related quality of life (HRQoL) after treatment
      between braced and surgically treated patients are not well explored, this study
      aimed to determine whether short-term differences exist in HRQoL between
      adolescents treated with a brace or treated surgically. A cross-sectional
      analysis of HRQoL was made of 109 patients with adolescent idiopathic scoliosis
      who, after completing treatment, filled out the Dutch SRS-22 Patient
      Questionnaire. All patients had been treated either with a brace or surgery, or
      with a brace followed by surgery. Patients treated surgically had significantly
      higher mean scores in the satisfaction with management domain than those treated
      with a brace. No other consistent differences in HRQoL were found between
      patients treated with a brace and patients treated surgically. Gender, curve type
      and curve size had no relevant effect on HRQoL. We conclude that short-term
      differences in HRQoL after treatment in adolescent patients with idiopathic
      scoliosis are negligible and cannot support preference of one treatment above the
      other.

PMID- 16609856
TI  - Genetic manipulation of the biosynthetic process leading to phoslactomycins,
      potent protein phosphatase 2A inhibitors.
AB  - Phoslactomycins (PLMs) represent an unusual structural class of natural products
      secreted by various streptomycetes, containing an alpha,beta-unsaturated delta
      lactone, an amino group, phosphate ester, conjugated diene and a cyclohexane
      ring. Phosphazomycins, phospholines and leustroducsins contain the same
      structural moieties, varying only in the acyl substituent at the C-18 hydroxyl
      position. These compounds possess either antifungal or antitumor activities or
      both. The antitumor activity of the PLM class of compounds has been attributed to
      a potent and selective inhibition of protein phosphatase 2A (PP2A). The cysteine
      269 residue of PP2Ac-subunit has been shown to be the site of covalent
      modification by PLMs. In this article, we review previous work on the isolation,
      structure elucidation and biological activities of PLMs and related compounds and
      current status of our work on both PLM stability and genetic manipulation of the
      biosynthetic process. Our work has shown that PLM B is surprisingly stable in
      solution, with a pH optimum of 6. Preliminary biosynthetic studies utilizing
      isotopically labeled shikimic acid and cyclohexanecarboxylic acid (CHC) suggested
      PLM B to be a polyketide-type antibiotic synthesized using CHC as a starter unit.
      Using a gene (chcA) from a set of CHC-CoA biosynthesis genes from Streptomyces
      collinus as a probe, a 75 kb region of 29 ORFs encoding PLM biosynthesis was
      located in the genome of Streptomyces sp. strain HK803. Analysis and subsequent
      manipulation of plmS2 and plmR2 in the gene cluster has allowed for rational
      engineering of a strain that produces only one PLM analog, PLM B, at ninefold
      higher titers than the wild type strain. A strain producing PLM G (the
      penultimate intermediate in PLMs biosynthesis) has also been generated. Current
      work is aimed at selective in vitro acylation of PLM G with various carboxylic
      acids and a precursor-directed biosynthesis in a chcA deletion mutant with the
      aim of generating novel PLM analogs.

PMID- 16609858
TI  - Quantifier variables of the back surface deformity obtained with a noninvasive
      structured light method: evaluation of their usefulness in idiopathic scoliosis
      diagnosis.
AB  - New noninvasive techniques, amongst them structured light methods, have been
      applied to study rachis deformities, providing a way to evaluate external back
      deformities in the three planes of space. These methods are aimed at reducing the
      number of radiographic examinations necessary to diagnose and follow-up patients
      with scoliosis. By projecting a grid over the patient's back, the corresponding
      software for image treatment provides a topography of the back in a color or gray
      scale. Visual inspection of back topographic images using this method immediately
      provides information about back deformity, but it is important to determine
      quantifier variables of the deformity to establish diagnostic criteria. In this
      paper, two topographic variables [deformity in the axial plane index (DAPI) and
      posterior trunk symmetry index (POTSI)] that quantify deformity in two different
      planes are analyzed. Although other authors have reported the POTSI variable, the
      DAPI variable proposed in this paper is innovative. The upper normality limit of
      these variables in a nonpathological group was determined. These two variables
      have different and complementary diagnostic characteristics, therefore we devised
      a combined diagnostic criterion: cases with normal DAPI and POTSI (DAPI < or =
      3.9% and POTSI < or = 27.5%) were diagnosed as nonpathologic, but cases with high
      DAPI or POTSI were diagnosed as pathologic. When we used this criterion to
      analyze all the cases in the sample (56 nonpathologic and 30 with idiopathic
      scoliosis), we obtained 76.6% sensitivity, 91% specificity, and a positive
      predictive value of 82%. The interobserver, intraobserver, and interassay
      variability were studied by determining the variation coefficient. There was good
      correlation between topographic variables (DAPI and POTSI) and clinical variables
      (Cobb's angle and vertebral rotation angle).

PMID- 16609859
TI  - Anterior dual rod instrumentation in idiopathic thoracic scoliosis.
AB  - For anterior correction and instrumentation of thoracic curves single rod
      techniques are widely used. Disadvantages of this technique include screw
      pullouts, rod fractures and limited control of kyphosis. This is a prospective
      study of 23 consecutive patients with idiopathic thoracic scoliosis treated with
      a new anterior dual rod system. Aim of the study was to evaluate the safety and
      efficacy of this new technique in the surgical treatment of idiopathic thoracic
      scoliosis. To the best knowledge of the authors, this is the largest series on
      dual rod dual screw instrumentation over the entire fusion length in thoracic
      scoliosis. Twenty-three patients with an average age of 15 years were surgically
      treated with a new anterior dual rod system through a standard open double
      thoracotomy approach. Average clinical and radiological follow-up was 28 months
      (24-46 months). Fusion was carried out mostly from end-to-end vertebra. The
      primary curve was corrected from 66.6 degrees to 28.3 degrees (57.5% correction)
      with an average loss of correction of 2.0 degrees at Cobb levels and of 1.3
      degrees at fusion levels. Spontaneous correction of the secondary lumbar curve
      averaged 43.2% (preoperative Cobb angle 41.2 degrees ). The apical vertebral
      rotation was corrected by 41.1% with a consecutive correction of the rib hump of
      clinically 66.7%. The thoracic kyphosis measured 29.2 degrees preoperatively and
      33.6 degrees at follow-up. In seven patients with a preoperative hyperkyphosis of
      on average 47.3 degrees thoracic kyphosis was corrected to 41.0 degrees . This
      new instrumentation enables an entire dual rod instrumentation over the whole
      thoracic fusion length. It offers primary stability without the need of
      postoperative bracing. Dual screw dual rod instrumentation offers the advantages
      of a high screw pullout resistance, an increased overall stability and
      satisfactory sagittal plane control.

PMID- 16609860
TI  - Complete assignment of the chromosomes of Gossypium hirsutum L. by translocation
      and fluorescence in situ hybridization mapping.
AB  - Significant progress has been made in the construction of genetic maps in the
      tetraploid cotton Gossypium hirsutum. However, six linkage groups (LGs) have
      still not been assigned to specific chromosomes, which is a hindrance for
      integrated genetic map construction. In the present research, specific bacterial
      artificial chromosome (BAC) clones constructed in G. hirsutum acc. TM-1 for these
      six LGs were identified by screening the BAC library using linkage group-specific
      simple-sequence repeats markers. These BAC clones were hybridized to ten
      translocation heterozygotes of G. hirsutum. L as BAC-fluorescence in situ
      hybridization probes, which allowed us to assign these six LGs A01, A02, A03,
      D02, D03, and D08 to chromosomes 13, 8, 11, 21, 24, and 19, respectively.
      Therefore, the 13 homeologous chromosome pairs have been established, and we have
      proposed a new chromosome nomenclature for tetraploid cotton.

PMID- 16609861
TI  - Measurement of cardiac ventricular volumes using multidetector row computed
      tomography: comparison of two- and three-dimensional methods.
AB  - This study compared a three-dimensional volumetric threshold-based method to a
      two-dimensional Simpson's rule based short-axis multiplanar method for measuring
      right (RV) and left ventricular (LV) volumes, stroke volumes, and ejection
      fraction using electrocardiography-gated multidetector computed tomography (MDCT)
      data sets. End-diastolic volume (EDV) and end-systolic volume (ESV) of RV and LV
      were measured independently and blindly by two observers from contrast-enhanced
      MDCT images using commercial software in 18 patients. For RV and LV the three
      dimensionally calculated EDV and ESV values were smaller than those provided by
      two-dimensional short axis (10%, 5%, 15% and 26% differences respectively).
      Agreement between the two methods was found for LV (EDV/ESV: r=0.974/0.910,
      ICC=0.905/0.890) but not for RV (r=0.882/0.930, ICC=0.663/0.544). Measurement
      errors were significant only for EDV of LV using the two-dimensional method.
      Similar reproducibility was found for LV measurements, but the three-dimensional
      method provided greater reproducibility for RV measurements than the two
      dimensional. The threshold value supported three-dimensional method provides
      reproducible cardiac ventricular volume measurements, comparable to those
      obtained using the short-axis Simpson based method.

PMID- 16609862
TI  - Low-dose ECG-gated 64-slices helical CT angiography of the chest: evaluation of
      image quality in 105 patients.
AB  - The purpose of this study was to evaluate image quality of low-dose
      electrocardiogram (ECG)-gated multislice helical computed tomography (CT)
      angiograms of the chest. One hundred and five consecutive patients with a regular
      sinus rhythm (72 men; 33 women) underwent ECG-gated CT angiographic examination
      of the chest without administration of beta blockers using the following
      parameters: (a) collimation 32 x 0.6 mm with z-flying focal spot for the
      acquisition of 64 overlapping 0.6-mm slices, rotation time 0.33 s, pitch 0.3; (b)
      120 kV, 200 mAs; (c) use of two dose modulation systems, including adjustment of
      the mAs setting to the patient's size and anatomical shape and an ECG-controlled
      tube current. Subjective and objective image quality was evaluated by two
      radiologists in consensus on 3-mm-thick scans reconstructed at 55% of the
      response rate (RR) interval. The population and protocol characteristics
      included: (a) a mean [+/-standard deviation (SD)] body mass index (BMI) of 24.47
      (+/-4.64); (b) a mean (+/-SD) heart rate of 72.04 (+/-15.76) bpm; (c) a mean (+/
      SD) scanning time of 18.3 (+/-2.73) s; (d) a mean (+/-SD) dose-length product
      (DLP) value of 260.57 (+/-83.67) mGy/cm; (e) an estimated average effective dose
      of 4.95 (+/-1.59) mSv. Subjective noise was depicted in a total of nine
      examinations (8.5%), always rated as mild. Objective noise was assessed by
      measuring the standard deviation of pixel values in a homogeneous region of
      interest within the trachea and descending aorta; SD was 15.91 HU in the trachea
      and 22.16 HU in the descending aorta, with no significant difference in the mean
      value of the standard deviations between the four categories of BMI except for
      obese patients, who had a higher mean SD within the aorta. Interpolation
      artefacts were depicted in 22 patients, with a mean heart rate significantly
      lower than that of patients without interpolation artifacts, rated as mild in 11
      patients and severe in 11 patients. The severity of interpolation artefacts was
      significantly linked to a low heart rate in affected patients. The overall image
      quality of CT scans was rated as diagnostic in 94 patients (89.5%) while 11
      examinations (10.5%) were found to be partially nondiagnostic owing to the cyclic
      presence of severe interpolation artefacts, which can be compensated for by
      additional reconstructions at a different temporal window. In these cases,
      interpolation artefacts could have been avoided by reducing the pitch from 0.3 to
      0.2 at the expense of increased patient dose. Low-dose ECG-gated CT angiograms of
      the chest can be obtained in routine clinical practice with 64-slice CT
      technology without altering the diagnostic value of CT scans.

PMID- 16609863
TI  - Cutting balloons for the treatment of vascular stenoses.
AB  - The aim of this article is to review the mechanism, technical characteristics,
      biological response and clinical applications of cutting balloon angioplasty in
      peripheral vessels. The cutting balloon is a non-compliant, balloon catheter
      equipped with three-to-four microtome-sharp atherotomes. When used appropriately,
      it is safe and easy to use, with a high immediate success rate and few
      complications, provided oversizing is avoided. There is some evidence that pre
      dilation with a standard or high-pressure balloon may also predispose to vascular
      rupture. The cutting balloon has proved to be beneficial in treating difficult
      complex lesions in the coronary arteries. Early experience in non-coronary
      vessels shows that cutting balloon angioplasty can be used to treat peripheral
      bypass anastomotic and haemodialysis fistula stenoses that are resistant to
      conventional high-inflation pressures. Its application in de novo peripheral
      arterial lesions and non-coronary in-stent restenosis is still under discussion.
      Theoretically, this device induces a smaller degree of vessel wall injury
      localised to the area of incisions and sparing the interincisional segments;
      however, this postulated reduction in restenosis rates has not been confirmed in
      clinical practice.

PMID- 16609864
TI  - Histamine receptors in human detrusor smooth muscle cells: physiological
      properties and immunohistochemical representation of subtypes.
AB  - The potent inflammatory mediator histamine is released from activated mast cells
      in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes
      involved in the intracellular calcium response of cultured smooth muscle cells
      (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from
      human detrusor biopsies. The distribution of histamine receptor subtypes was
      addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a
      maximum of 92% of the cells (n=335), being more effective than carbachol (70%,
      n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant
      lower numbers of reacting cells (60, 48 and 54%). Histamine receptor
      immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine
      induced calcium increase is mediated by distinct histamine receptors. Thus, pre
      therapeutic evaluation of histamine receptor expression in IC patients may help
      to optimize therapy by using a patient-specific cocktail of subtype-specific
      histamine receptor antagonists.

PMID- 16609865
TI  - Synovial hemangiohamartomas of the knee joint.
AB  - Hemangioma or vascular malformation of the synovium is rare and presents a
      difficult problem in diagnosis and treatment. A long history of joint pain and
      recurrent non-traumatic hemarthrosis usually draws attention to the hemangioma of
      the knee joint. The lesion can be seen in two different formations; the synovial
      hemangioma or the arteriovenous malformation named as hemangiohamartomas, both of
      which involve the synovium and cause non-traumatic episodes of hemarthrosis. MRI
      scanning together with arthroscopy is a diagnostic tool to demonstrate the extent
      and the nature of the lesion. We treated the three patients at different ages.
      All patients underwent standard radiographic examination, CT scans, MRI and
      diagnostic arthroscopy. After frozen section taken via arthroscopically, the
      lesions were excised by arthrotomy. The mean follow-up was 38 months (31-45) and
      all patients are asymptomatic postoperatively. Three additional cases and a
      review of the literature are presented because of the rarity of the lesion.

PMID- 16609866
TI  - Two to nineteen years follow-up of arthroscopic meniscal repair using the outside
      in technique: a retrospective study.
AB  - PURPOSE: To perform a long-term follow-up evaluation of the outside-in technique
      of arthroscopic meniscal repair. TYPE OF STUDY: Retrospective study. METHODS:
      Between the years 1986 and 2002, 93 cases of arthroscopic meniscal repair using
      the outside-in technique have been operated by the senior author (F.L.). Forty
      one patients were available for the follow-up evaluation with a mean follow-up of
      11.71 years. The International Knee Documentation Committee (IKDC), the modified
      Lysholm score, the SF-36 (short form 36) health survey score, a visual analogue
      scale (VAS) for assessment of patients' satisfaction and another VAS for
      assessment of patients' pain were used retrospectively to evaluate the patients.
      We also used the Kellgren and Lawrence (K/L) classification of osteoarthritis to
      evaluate the preoperative X-rays and the X-rays done at the time of the follow-up
      evaluation. Failure was defined as having a meniscectomy procedure post
      operatively. RESULTS: From the 93 patients, 52 could not be retrieved for the
      follow-up evaluation, while 41 were available for it; 36 patients were clinically
      successful and 5 were considered as failure. Thirty-six patients were classified
      as grade "A" in the objective IKDC score, mean modified Lysholm score was 87.29
      (SD 16.43), while mean SF-36 score was 85.73 (SD 14.17). The results of the VAS
      for operation satisfaction ranging from -10 to +10 revealed that the mean of the
      answers was 8.05 (SD 2.99). The results of the VAS for pain ranging from 0 to 10
      revealed that the mean of the patients' pain at the time of the follow-up
      evaluation was 1.8 (SD 2.42). Twenty out of 24 (only 24 preoperative X-rays were
      available) were classified as having no osteoarthritis pre-operatively, whereas
      only 12 out of the 41 patients were classified as having no osteoarthritis
      (normal) at the time of the follow-up evaluation according to the K/L
      classification which indicates progression of osteoarthritis. No complications
      related to the outside-in arthroscopic meniscal repair procedure were reported.
      CONCLUSION: We conclude that arthroscopic meniscal repair using the outside-in
      technique is a safe surgical procedure with a good clinical outcome.

PMID- 16609867
TI  - The FoxP subclass in Xenopus laevis development.
AB  - We have investigated the sequences and the expression patterns of different
      members of the Xenopus laevis FoxP gene subfamily during embryogenesis. Low
      stringency hybridisation of a tadpole cDNA library with an xlFoxP2 fragment led
      to the isolation of several splice variants of xlFoxP1, xlFoxP2 and xlFoxP4.
      These variants do not only differ by utilisation of different leader exons, but
      also by alternative usage of coding exons thereby leading to functional
      alterations. For xlFoxP1b, we show that insertion of an additional exon disrupts
      binding to the co-repressor C-terminal binding protein1. Temporal and spatial
      expression patterns of xlFoxP2 and xlFoxP4 were analysed by RT-PCR and by whole
      mount in situ hybridisation. xlFoxP2 transcripts are detected from mid-gastrula
      to late tadpole stages and are found to be localised to pronephros, branchial
      arches and distinct structures of the hind-, mid- and forebrain, including the
      ciliary marginal zone of the retina. xlFoxP4 RNA is already present in early
      cleavage stage embryos and accumulates from midblastula until the end of
      embryogenesis. Localised expression is found within the anterior neural fold, in
      the mid- and hindbrain, in the branchial arches as well as in the pancreas.

PMID- 16609868
TI  - The existence of all three ParaHox genes in the clitellate annelid, Perionyx
      excavatus.
AB  - A ParaHox gene cluster is composed of three genes (Gsx, Xlox, and Cdx). It has
      been proposed that all three ParaHox genes were present in the last common
      ancestor to the lophotrochozoan protostomes and the deuterostomes and that gene
      loss event has occurred in the ecdysozoan lineage. In this paper, we report the
      existence of all three ParaHox genes in Perionyx excavatus, a clitellate annelid.
      Although orthologs of each of the three ParaHox genes were previously discovered
      from other lopotrochozoan taxa, this study constitutes the first reported
      isolation of all three ParaHox genes in the same clitellate species.

PMID- 16609869
TI  - Drosophila RhoGAP68F is a putative GTPase activating protein for RhoA
      participating in gastrulation.
AB  - The Rho family small GTPases Rho, Rac, and Cdc42 regulate cell shape and motility
      through the actin cytoskeleton. These proteins cycle between a GTP-bound "on"
      state and a GDP-bound "off" state and are negatively regulated by GTPase
      activating proteins (GAPs), which accelerate the small GTPase's intrinsic
      hydrolysis of bound GTP to GDP. Drosophila RhoGAP68F is similar to the mammalian
      protein p50RhoGAP/Cdc42GAP, which exhibits strong GAP activity toward Cdc42. We
      find that, despite the strong similarities between RhoGAP68F and
      p50RhoGAP/Cdc42GAP, RhoGAP68F is most effective as a GAP for RhoA. These in vitro
      data are supported by the in vivo analysis of mutants in RhoGAP68F. We
      demonstrate through the characterization of two alleles of the RhoGAP68F gene
      that RhoGAP68F participates in gastrulation of the embryo, a morphogenetic event
      driven by cell constriction that involves RhoA signaling. We propose that
      RhoGAP68F functions as a regulator of RhoA signaling during gastrulation.

PMID- 16609870
TI  - The presence of anti-mitochondrial antibodies in Chinese patients with liver
      involvement in systemic lupus erythematosus.
AB  - Sixty-six hospitalized patients with systemic lupus erythematosus (SLE) were
      enrolled into this study. The test for anti-mitochondrial antibodies (AMAs) was
      performed and biochemical parameters were determined. AMAs were detected in 15 of
      the 66 patients with SLE. Meanwhile, we compared enzymatic levels in AMA-positive
      and -negative patients and found that serum aminotransferase levels were
      significantly higher in AMA-positive patients than in AMA-negative individuals.
      Furthermore, we found a positive correlation between serum AMA titration and
      serum aminotransferase levels. This study suggests that AMAs might contribute to
      the elevation of aminotransferases. Although much remains to be learned about the
      pathogenesis of autoimmune liver disease associated with AMAs, this report might
      provide greater insight into the metabolic mechanisms of AMAs in AMA-positive
      patients.

PMID- 16609871
TI  - [Dis-social personality disorder].
AB  - Deviant behavior is gaining in clinical importance if it is founded on stable,
      characteristic, and enduring patterns of psychopathologically relevant
      personality traits which have their onset in childhood or adolescence. The
      classification of these traits shows variations, so that a distinction between
      the ICD-10 diagnosis of dis-social personality disorder, DSM-IV diagnosis of
      antisocial personality disorder, and the concept "psychopathy" is necessary. Our
      knowledge about the biological basis of antisocial behavior includes
      neurophysiologic, psychophysiologic, and genetic findings. Also relevant are
      results of neurotransmitter studies and structural resp. functional neuroimaging
      findings. Psychosocial risk factors include parental deficits, rejection,
      disregard, unstable relations, and abuse. Efficient psychotherapeutic treatment
      is cognitive-behavioral. Pharmacologic treatment is largely "off-label". The
      diagnosis of antisocial and dis-social personality disorders allows no
      conclusions on criminal responsibility. In addition to psychiatric diagnostics,
      considerations on the severity of the disorder and its effects on the ability to
      inhibit actions are necessary.

PMID- 16609872
TI  - The consequence of species loss on ecosystem nitrogen cycling depends on
      community compensation.
AB  - Repercussions of species loss on ecosystem processes depend on the effects of the
      lost species as well as the compensatory responses of the remaining species in
      the community. We experimentally removed two co-dominant plant species and added
      a 15N tracer in alpine tundra to compare how species' functional differences
      influence community structure and N cycling. For both of the species, production
      compensated for the biomass removed by the second year. However, the responses of
      the remaining species depended on which species was removed. These differences in
      compensation influenced how species loss impacted ecosystem processes. After the
      removal of one of the co-dominant species, Acomastylis rossii, there were few
      changes in the relative abundance of the remaining species, and differences in
      functioning could be predicted based on effects associated with the removed
      species. In contrast, the removal of the other co-dominant, Deschampsia
      caespitosa, was associated with subsequent changes in community structure
      (species relative abundances and diversity) and impacts on ecosystem properties
      (microbial biomass N, dissolved organic N, and N uptake of subordinate species).
      Variation in compensation may contribute to the resulting effects on ecosystem
      functioning, with the potential to buffer or accelerate the effects of species
      loss.

PMID- 16609873
TI  - Fitness consequences of pheromone production and host selection strategies in a
      tree-killing bark beetle (Coleoptera: Curculionidae: Scolytinae).
AB  - Timing of arrival at a resource often determines an individual's reproductive
      success. Tree-killing bark beetles can reproduce in healthy trees by attacking in
      adequate numbers to overcome host defences that could otherwise be lethal. This
      process is mediated by aggregation and antiaggregation pheromones. Beetles that
      arrive early in such a "mass attack" must contend with undiminished tree
      defences, and produce enough pheromones to attract more beetles, but have a head
      start on gallery construction and egg-laying. Beetles that arrive late may be
      impeded by competition and diminishing availability of phloem, but should
      experience fewer costs associated with pheromone production and battling tree
      defences. We investigated relationships between timing of arrival, body size,
      pheromone production and fitness in the southern pine beetle, Dendroctonus
      frontalis. In field experiments, we captured beetles that arrived early
      (pioneers) and late on slash pine trees, Pinus elliottii, and measured pheromone
      amounts in their hindguts. We marked gallery entrances of beetles as they landed
      on a tree and measured their reproductive success after the attack terminated. We
      found no difference in body size or pheromone amounts between early and late
      arrivers. Most beetles arrived at the middle of the attack sequence, and
      excavated longer galleries per day than early arrivers. The number of offspring
      produced per day by beetles that established galleries midway through mass attack
      was higher than those that arrived early or very late in the sequence. Our
      results suggest that beetles do not exhibit adaptive phenotypic plasticity in pre
      landing pheromone production, depending on the extent of previous colonisation of
      a host. Rather, it appears that stabilising selection favours beetles that attack
      in the middle of the sequence, and contributes to attack synchrony. Synchronous
      attack on trees is essential before population booms characteristic of tree
      killing bark beetles can occur in nature.

PMID- 16609874
TI  - Anaemia in diabetic patients with chronic kidney disease--prevalence and
      predictors.
AB  - AIMS/HYPOTHESIS: We investigated the relationship between haemoglobin (Hb) and
      diabetes in patients with renal disease. SUBJECTS, MATERIALS AND METHODS: All
      adult patients with stable chronic kidney disease attending renal or diabetic
      outpatient clinics in a six-month period were identified. Patients' notes and
      electronic patient records were used to build a comprehensive biochemical and
      clinical database. Results were analysed for the predictors of Hb, the severity
      of anaemia in both groups and the relative impact of diabetes on haemoglobin and
      anaemia. RESULTS: The study group consisted of 468 patients, of whom 204 had
      diabetes and 264 did not. At every level of renal function haemoglobin levels
      were lower by an average of 10 g/l in subjects with diabetes than in those
      without. Likewise, anaemia was found to occur at an earlier stage of chronic
      kidney disease (and to be of greater severity) in diabetic patients. Independent
      predictors of haemoglobin included female sex, diabetes, renal function and serum
      albumin, with diabetes and renal function being the greatest predictors. Multiple
      logistic regression showed that patients with diabetes had an odds ratio of 4 for
      being anaemic. Had we used an estimated GFR of less than 60 ml/min to trigger
      investigation of anaemia, we would have detected 85% of anaemic patients.
      CONCLUSIONS/INTERPRETATION: Anaemia is frequently found in diabetic patients with
      renal disease, occurs earlier and is more severe than in similar but non-diabetic
      subjects. In contrast to previous publications, our findings suggest that anaemia
      is prevalent at the earliest stages of chronic kidney disease. We advocate an
      estimated GFR threshold of <60 ml/min to trigger investigation for anaemia in
      diabetic subjects.

PMID- 16609875
TI  - Macrophage-conditioned medium inhibits the differentiation of 3T3-L1 and human
      abdominal preadipocytes.
AB  - AIMS/HYPOTHESIS: In obesity, a limited adipogenic capacity may promote adipocyte
      hypertrophy and increase the risk of insulin resistance and type 2 diabetes.
      Recent data indicate that macrophages reside within adipose tissue in obese
      rodents and humans. We hypothesised that secreted macrophage factors may inhibit
      adipogenesis. MATERIALS AND METHODS: Conditioned media from cultured murine J774
      or human THP-1 macrophages were collected, and added to either murine 3T3-L1
      preadipocytes or human abdominal stromal preadipocytes from subcutaneous or
      omental fat depots. RESULTS: Macrophage-conditioned medium (MacCM) strongly
      inhibited 3T3-L1 adipogenesis. Dose-response studies with J774-MacCM revealed
      that 80 and 100% of J774-MacCM completely suppressed triacylglycerol accumulation
      as well as the induction of fatty acid synthase, peroxisome proliferator
      activated receptor gamma, CCAAT/enhancer binding protein alpha, and adiponectin.
      Similar inhibitory effects on 3T3-L1 preadipocytes were observed with THP-1
      MacCM. Differentiation of human abdominal subcutaneous stromal preadipocytes was
      moderately reduced (subcutaneous>omental) by J744-MacCM. In contrast, the
      differentiation of both subcutaneous and omental stromal preadipocytes was
      completely inhibited by THP-1-MacCM, as determined on the basis of morphology and
      triacylglycerol accumulation, as well as fatty acid synthase and adiponectin
      protein expression. CONCLUSIONS/INTERPRETATION: Secreted macrophage products
      inhibit the differentiation of 3T3-L1 preadipocytes as well as human abdominal
      stromal preadipocytes.

PMID- 16609876
TI  - Comment to: Martin S, Schneider B, Heinemann L et al (2006) Self-monitoring of
      blood glucose in type 2 diabetes and long-term outcome: an epidemiological cohort
      study. Diabetologia 49:271-278.

PMID- 16609877
TI  - Exendin-4 treatment improves metabolic control after rat islet transplantation to
      athymic mice with streptozotocin-induced diabetes.
AB  - AIMS/HYPOTHESIS: Early islet graft survival is crucial in determining the outcome
      after clinical islet transplantation. Exendin-4 has anti-apoptotic and beta cell
      proliferative properties, which could improve islet graft survival and function.
      The aim of these studies was to evaluate the effect of exendin-4 on graft
      function after islet transplantation. MATERIALS AND METHODS: Rat islets were
      transplanted under the kidney capsule of diabetic athymic mice. First, we
      performed a dose-finding study and found that 30 islets just failed to cure
      diabetic mice. In the following two studies, we transplanted 30 islets and
      treated the mice that had received these islets with exendin-4 i.p. (100
      ng/mouse) once daily for 1 week. Blood glucose levels and body weights were used
      as evaluation criteria. In the short-term study evaluation was done at day 8.
      This study was followed by a long-term study that was evaluated at 4 weeks. In
      this study, islets were precultured with exendin-4 (0.1 nmol/l) in addition to
      the treatment given to mouse-recipients of transplanted islets. The cured mice
      underwent an intraperitoneal glucose tolerance test (IPGTT). RESULTS: In the
      short-term study, 63% of exendin-4-treated mice achieved graft function compared
      with 21% of untreated mice (p = 0.033). In the long-term study, 88% of treated
      mice had functioning grafts compared with 22% of controls (p = 0.015). Cured mice
      showed a normal response in the IPGTT, comparable to that of healthy mice.
      Exendin-4-treated mice gained significantly more weight than their untreated
      counterparts. CONCLUSIONS/INTERPRETATION: Islet preculture and a short course of
      therapy with exendin-4 improves metabolic control after rat islet transplantation
      in athymic mice. The beneficial effect lasts beyond the treatment period.

PMID- 16609878
TI  - Digami too?

PMID- 16609879
TI  - Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes
      diagnosed in the first 6 months of life, with the phenotype determined by
      genotype.
AB  - AIMS/HYPOTHESIS: Heterozygous activating mutations in KCNJ11, which encodes the
      Kir6.2 subunit of the pancreatic ATP-sensitive potassium (K(ATP)) channel, cause
      both permanent and transient neonatal diabetes. A minority of patients also have
      neurological features. The identification of a KCNJ11 mutation has important
      therapeutic implications, as many patients can replace insulin injections with
      sulfonylurea tablets. We aimed to determine the age of presentation of patients
      with KCNJ11 mutations and to examine if there was a relationship between genotype
      and phenotype. SUBJECTS AND METHODS: KCNJ11 was sequenced in 239 unrelated
      patients from 21 countries, who were diagnosed with permanent diabetes before 2
      years of age. RESULTS: Thirty-one of the 120 patients (26%) diagnosed in the
      first 26 weeks of life had a KCNJ11 mutation; no mutations were found in the 119
      cases (0%) diagnosed after this age. Fourteen different heterozygous mutations
      were identified, with the majority resulting from de novo mutations. These
      include seven novel mutations: H46Y, R50Q, G53D C166Y, K170T, L164P and Y330S.
      All 11 probands with the most common mutation, R201H, had isolated diabetes. In
      contrast, developmental delay in addition to diabetes was seen in four of five
      probands with the V59M mutation and two of four with the R201C mutation. Five
      patients with developmental delay, epilepsy and neonatal diabetes (DEND) syndrome
      had unique mutations not associated with other phenotypes.
      CONCLUSIONS/INTERPRETATION: KCNJ11 mutations are a common cause of permanent
      diabetes diagnosed in the first 6 months and all patients diagnosed in this age
      group should be tested. There is a strong genotype-phenotype relationship with
      the mutation being an important determinant of associated neurological features.

PMID- 16609880
TI  - Reduced plasma adiponectin concentrations may contribute to impaired insulin
      activation of glycogen synthase in skeletal muscle of patients with type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: Circulating levels of adiponectin are negatively associated with
      multiple indices of insulin resistance, and the concentration is reduced in
      humans with insulin resistance and type 2 diabetes. However, the mechanisms by
      which adiponectin improves insulin sensitivity remain unclear. SUBJECTS AND
      METHODS: Combining euglycaemic-hyperinsulinaemic clamp studies with indirect
      calorimetry and skeletal muscle biopsies, we examined the relationship between
      plasma adiponectin and parameters of whole-body glucose and lipid metabolism, and
      muscle glycogen synthase (GS) activity in 51 Caucasians (ten lean, 21 obese and
      20 with type 2 diabetes). RESULTS: Plasma adiponectin was significantly reduced
      in type 2 diabetic compared with obese and lean subjects. In lean and obese
      subjects, insulin significantly reduced plasma adiponectin, but this response was
      blunted in patients with type 2 diabetes. Plasma adiponectin was positively
      associated with insulin-stimulated glucose disposal (r = 0.48), glucose oxidation
      (r = 0.54), respiratory quotient (r = 0.58) and non-oxidative glucose metabolism
      (r = 0.38), and negatively associated with lipid oxidation during insulin
      stimulation (r = -0.60) after adjustment for body fat (all p < 0.01). Most
      notably, we found a positive association between plasma adiponectin and insulin
      stimulation of GS activity in skeletal muscle (r = 0.44, p < 0.01).
      CONCLUSIONS/INTERPRETATION: Our results indicate that plasma adiponectin may
      enhance insulin sensitivity by improving the capacity to switch from lipid to
      glucose oxidation and to store glucose as glycogen in response to insulin, and
      that low adiponectin may contribute to impaired insulin activation of GS in
      skeletal muscle of patients with type 2 diabetes.

PMID- 16609881
TI  - Regulation of adiponectin receptors in hepatocytes by the peroxisome proliferator
      activated receptor-gamma agonist rosiglitazone.
AB  - AIMS/HYPOTHESIS: Adiponectin is an adipocyte-derived hormone that plays a
      critical role in the development of type 2 diabetes via interaction with
      adiponectin receptors 1 (ADIPOR1) and 2 (ADIPOR2). Rosiglitazone is a peroxisome
      proliferator-activated receptor-gamma (PPARG) agonist that is widely used in the
      treatment of type 2 diabetes. We hypothesised that rosiglitazone regulates lipid
      and glucose metabolism through modulation of the expression of adiponectin
      receptors in the liver. METHODS: The expression of ADIPOR1 and ADIPOR2 was
      analysed in HepG2 hepatocytes. The promoters of adiponectin receptors were
      isolated and used to analyse the transcriptional regulation. The expression of
      adiponectin receptors in the liver was determined in mice treated with
      rosiglitazone. RESULTS: Rosiglitazone elevated the mRNA and protein levels of
      ADIPOR2 and stimulated ADIPOR2 promoter in HepG2 cells. Analysis with the ADIPOR2
      promoter revealed a putative rosiglitazone-responsive region that contained a
      glucocorticoid receptor (GR)-binding element. The GR agonist dexamethasone
      synergised with rosiglitazone to stimulate the ADIPOR2 promoter wheras the GR
      antagonist RU486 abolished this stimulation. Treatment of mice with rosiglitazone
      elevated the expression of ADIPOR2 in the liver. CONCLUSIONS/INTERPRETATION: This
      study indicates that rosiglitazone can elevate the expression of ADIPOR2 in
      hepatocytes. Our data also suggest that the PPARG agonist rosiglitazone can
      interact functionally with a GR element in the ADIPOR2 promoter to mediate
      stimulation of transcription. This study thus reveals a new paradigm underlying
      the therapeutic effect of PPARG activators in the treatment of type 2 diabetes.

PMID- 16609882
TI  - A large-scale genetic association study of ossification of the posterior
      longitudinal ligament of the spine.
AB  - Research to date has identified several genes that are implicated in the etiology
      of ossification of the posterior longitudinal ligament of the spine (OPLL);
      however, their pathogenetic relevance remains obscure. The aim of this study is
      to identify susceptibility genes for OPLL through a large-scale case-control
      association study and to re-examine previously reported associations. A total of
      109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped
      for 711 sporadic OPLL patients and 896 controls. The differences in allelic and
      genotypic distribution between patients and controls were assessed using the chi
      (2) test with Bonferroni's correction. We also analyzed the association by
      separating patients into subgroups according to sex, age and the number of
      ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three
      genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant
      association. Previously reported associations of COL11A2, NPPS and TGFB1 with
      OPLL could not be reproduced. Further, no significant associations were detected
      in stratified analyses based on sex, age or the number of ossified vertebrae.
      TGFB3 warrants further investigation because it is located within a genomic
      region that has been positively linked with OPLL.

PMID- 16609883
TI  - Primary aneurysmal bone cyst of the maxillary sinus in a child: case report and
      review of the literature.
AB  - Our case report describes a primary aneurysmal bone cyst (ABC) of the maxillary
      sinus in a 12-year-old girl. The young patient presented with progressive
      diplopia, strabismus, and rapidly growing painless swelling of the left cheek.
      Imaging studies showed a heterogeneous contrast enhancing mass expanding the left
      maxillary sinus. The lesion was completely resected endoscopically and
      histological examination reported it as an ABC. The patient recovered well and is
      free of recurrence 9 months following surgery. ABC is a benign lesion usually
      associated with other bone pathology (fibrous dysplasia). It may behave
      aggressively and invade the orbit; so resection is necessary. Minimally invasive
      techniques such as endoscopic sinus surgery can be performed successfully in
      select cases. Long follow up is important because recurrence may occur, in which
      case further resection is warranted.

PMID- 16609884
TI  - [Medico-legal aspects of the use of fentanyl patches].
AB  - The use of fentanyl patches has become accepted as standard in Germany for the
      treatment of chronic and cancer pain. Recently generic fentanyl patches were
      launched but in contrast to the original patches the new patches are without
      labels concerning the concentration. There is not only a difference of ca 30% in
      the fentanyl concentration among the different generic patches, there is also a
      variation in the size. Especially in hospitals, nursing homes or in emergency
      cases the dose of the patches cannot be distinguished by doctors, nurses or other
      healthcare providers which can lead to overdoses or to withdrawal reactions with
      one of the strongest opioids available. In cases where problems occur the
      prescribing doctor will be held responsible.

PMID- 16609885
TI  - [Muscle relaxants in Germany 2005: a comparison of application customs in
      hospitals and private practices].
AB  - Aim of this study was to evaluate application customs of muscles relaxants in
      hospitals compared to their use in private practice. Of the 3,260 questionnaires
      sent-out, 66.9% could be analyzed. Of these 54% were from anesthetists in private
      practice, 41% from heads of hospital anesthesia departments and 5% from heads of
      level one hospital anesthesia departments. The first difference between private
      practices and hospitals was the number of available muscle relaxants: 87% of
      private practices use 1-3 relaxants, whereas 79% of hospitals use 3-5. Another
      apparent difference was the relationship between general anesthesia and the
      number of intubations: 60% of private practices have over 80% of general
      anesthesia cases, but only 50% of these patients are intubated. On the contrary,
      two thirds of the hospitals have 50-80% general anesthesia cases and 60-70% of
      patients are intubated. The main wish for an ideal muscle relaxant was
      independent of private practice or hospital, short onset time, followed by fast
      recovery. In accordance 74% of anesthetists in hospitals and 72% of anesthetists
      in private practice voiced the wish for a non-depolarizing succinylcholine
      substitute. The results of this nationwide survey suggest that time pressure in
      combination with an increased specialization of anesthetists in private practice
      are the main factors for availability and use of muscle relaxants in routine
      anesthesia.

PMID- 16609886
TI  - [Ventilation of an unprotected airway: evaluation of a new peak-inspiratory-flow
      and airway-pressure-limiting bag-valve-mask].
AB  - BACKGROUND: Currently 30 chest compressions and 2 ventilations with an
      inspiratory time of 1 s are recommended during cardiopulmonary resuscitation with
      an unprotected airway, thus spending about 15% instead of 40% of resuscitation
      time on ventilation. Time could be gained for chest compressions when reducing
      inspiratory time from 2 s to 1 s, however, stomach inflation may increase as
      well. METHODS: In an established bench model we evaluated the effect of reducing
      inspiratory time from 2 s to 1 s at different lower oesophageal sphincter
      pressure (LOSP) levels using a novel peak inspiratory-flow and peak airway
      pressure-limiting bag-valve-mask device (Smart-Bag). RESULTS: A reduction of
      inspiratory time from 2 s to 1 s resulted in significantly lower peak airway
      pressure with LOSP of 0.49 kPa (5 cm H2O), 0.98 kPa (10 cm H2O) and 1.47 kPa (15
      cm H2O) and an increase with 1.96 kPa (20 cm H2O). Lung tidal volume was reduced
      with 1 s compared to 2 s. When reducing inspiratory time from 2 s to 1 s, stomach
      inflation occurred only at a LOSP of 0.49 kPa (5 cm H2O). CONCLUSIONS: In this
      model of a simulated unprotected airway, a reduction of inspiratory time from 2 s
      to 1 s using the Smart-Bag resulted in comparable inspiratory peak airway
      pressure and lower, but clinically comparable, lung tidal volume. Stomach
      inflation occurred only at a LOSP of 0.49 kPa (5 cm H2O), and was higher with an
      inspiratory time of 2 s vs 1 s.

PMID- 16609887
TI  - Protective effects of thymoquinone and methotrexate on the renal injury in
      collagen-induced arthritis.
AB  - The goal of this investigation was to study the protective effects of
      thymoquinone (TQ) and methotrexate (MTX) on collagen-induced arthritis (CIA) in
      rats. On day 0 under ether anesthesia, the experimental groups were immunized
      with 0.5 mg native chick collagen II (CII) solubilized in 0.1 M acetic acid and
      emulsified in Freund's incomplete adjuvant. Control rats were gavaged with
      vehicle, whereas CII was administered intradermally. In addition, arthritis
      treated with TQ group received TQ (10 mg kg(-1) bw by gavage once a week for 3
      weeks starting on day 0); and arthritis treated with MTX group received MTX (MTX
      was suspended in corn oil and administered by gavage at 1 mg kg (-1) bw once a
      week for 3 weeks starting on day 0). A significant decrease in the incidence and
      severity of arthritis by clinical and radiographic assessments was found in
      recipients of therapy, compared with that of controls. The MTX treatment
      significantly (P<0.01) decreased the elevated serum NO, urea and creatinine in
      arthritic rats. Likewise, TQ treatment was also able to reduce significantly
      (P<0.05) serum NO, urea and creatinine levels, but to lesser extent than MTX. The
      histopathologic abnormalities are consistent with the hydropic epithelial cell
      degenerations and moderate tubular dilatation in the some proximal and distal
      tubules. The severity of the degenerative changes in most of the shrunken
      glomerules and vascular congestion were also observed in arthritic animals.
      Preventive treatment of TQ and especially MTX significantly inhibited kidney
      dysfunction and this histopathologic alterations. These studies indicate that TQ
      can be used similar to MTX as a safe and effective therapy for CIA and may be
      useful in the treatment of rheumatoid arthritis.

PMID- 16609888
TI  - Aristolochic acid I-induced DNA damage and cell cycle arrest in renal tubular
      epithelial cells in vitro.
AB  - DNA damage is a critical event preceding cellular apoptosis or necrosis. This
      study was carried out to investigate the effect of aristolochic acid I (AAI) on
      DNA damage and cell cycle in porcine proximal tubular epithelial cell lines (LLC
      PK1 cells). LLC-PK1 cells were stimulated with AAI at the concentrations of 80,
      320, and 1,280 ng/ml for 24 h. DNA damage was examined by comet assay and the
      cell cycle was assayed by flow cytometry (FCM), cellular apoptosis and lysis were
      examined simultaneously. Cellular nuclear changes were observed by electron
      microscopy and the expression of wild-type p53 protein and mRNA were measured by
      FCM and RT-PCR. We found that AAI-induced DNA damage prior to apoptosis and lysis
      in LLC-PK1 cells in a dose-dependent manner (P<0.01). The percentage of cells in
      the G2/M phase that were treated with AAI (320 and 1,280 ng/ml) for 24 h
      increased significantly (P<0.01). Electron micrographs showed the nuclear
      abnormalities in AAI-treated cells. The expression of p53 protein and mRNA did
      not change in the AAI-treated cells. AAI may cause DNA damage and cell cycle
      arrest in LLC-PK1 cells through a wild-type p53-independent pathway, prior to
      apoptosis or necrosis. This study on the molecular mechanism of AAI-induced
      toxicity may explain why tubular epithelial cells present limited proliferation
      and regeneration abilities in the clinical presentation of AAI-associated
      nephrotoxicity.

PMID- 16609889
TI  - Spontaneous plant regeneration in transformed roots and calli from Tylophora
      indica: Changes in morphological phenotype and tylophorine accumulation
      associated with transformation by Agrobacterium rhizogenes.
AB  - We examined the effects of genetic transformation by Agrobacterium rhizogenes on
      the production of tylophorine, a phenanthroindolizidine alkaloid, in the Indian
      medicinal plant, Tylophora indica. Transformed roots induced by the bacterium
      grew in axenic culture and produced shoots or embryogenic calli in the absence of
      hormone treatments. However, hormonal treatment was required to regenerate shoots
      in root explants of wild type control plants. Transformed plants showed
      morphological features typically seen in transgenic plants produced by A.
      rhizogenes, which include, short internodes, small and wrinkled leaves, more
      branches and numerous plagiotropic roots. Plants regenerated from transformed
      roots showed increased biomass accumulation (350-510% in the roots and 200-320%
      in the whole plants) and augmented tylophorine content (20-60%) in the shoots,
      resulting in a 160-280% increase in tylophorine production in different clones
      grown in vitro.

PMID- 16609890
TI  - Comparative analysis of 35S and lectin promoters in transgenic soybean tissue
      using an automated image acquisition system and image analysis.
AB  - Expression of the green fluorescent protein (gfp) gene, under regulatory control
      of either the constitutive 35S promoter or the developmentally-regulated lectin
      promoter was monitored and quantified using a newly-developed automated tracking
      system. The automated system consisted of a computer-controlled two-dimensional
      robotics table and a programmable image acquisition system, which was used to
      semi-continuously monitor gfp gene expression during development of transgenic
      soybean [Glycine max (L.) Merrill] somatic embryos. Quantitative analysis of GFP
      expression showed that, during somatic embryo proliferation and early
      development, expression of lectin-GFP was not detected. During late embryo
      development, expression of lectin-GFP gradually increased until the levels were
      similar to those of 35S-GFP. The use of an automated image collection system and
      image analysis facilitated the frequent monitoring and quantification of gfp gene
      expression on a large number of samples over an extended period of time.

PMID- 16609891
TI  - [Embryonic stem cells. Future perspectives].
AB  - Embryonic stem cells (ES cells) are able to differentiate into any cell type, and
      therefore represent an excellent source for cellular replacement therapies in the
      case of widespread diseases, for example heart failure, diabetes, Parkinson's
      disease and spinal cord injury. A major prerequisite for their efficient and safe
      clinical application is the availability of pure populations for direct cell
      transplantation or tissue engineering as well as the immunological compatibility
      of the transplanted cells. The expression of human surface markers under the
      control of cell type specific promoters represents a promising approach for the
      selection of cardiomyocytes and other cell types for therapeutic applications.
      The first human clinical trial using ES cells will start in the United States
      this year.

PMID- 16609893
TI  - [Ankle chondrocytes are more resistant to Interleukin-1 than chondrocytes derived
      from the knee].
AB  - BACKGROUND: The incidence of degenerative changes and osteoarthritis is lower in
      the ankle than in the knee joints. This cannot be explained exclusively with
      differences in anatomy and biomechanical properties of these two synovial joints.
      Previous studies have indicated distinct differences in the biochemical
      composition of the extracellular matrix of articular cartilage from knee and
      ankle joints. The aim of this study was to identify potential metabolic
      differences between knee and ankle joint chondrocytes using isolated cells to
      distinguish the secondary effects of the resident extracellular matrix from the
      primary matrix-independent effects of cellular differentiation. METHOD: Isolated
      knee and ankle chondrocytes from the same human donor were cultured in alginate
      beads and subsequently exposed to a three-day pulse of the catabolic cytokine
      interleukin-1 (IL-1) as a model of an inflammatory episode. The metabolism of
      proteoglycans (PG's) was analyzed as expressed changes in 35S-sulfate
      incorporation into glycosaminoglycans (GAG's). RESULTS: The presence of IL-1
      induced an inhibition of PG synthesis in knee and ankle articular chondrocytes.
      The 50% inhibitory concentration (IC50) of IL-1 was about 5 times lower for knee
      than for ankle chondrocytes. CONCLUSION: Ankle chondrocytes are more resistant to
      IL-1 induced inhibition of PG synthesis than chondrocytes from the knee.

PMID- 16609894
TI  - Reliability of CT-based tumor volumetry after intraarterial chemotherapy in
      patients with small carcinoma of the oral cavity and the oropharynx.
AB  - INTRODUCTION: The aim of the study was to evaluate the feasibility and
      consistency of CT-based tumor volumetry in patients with early carcinoma of the
      oral cavity and the oropharynx before and after intraarterial (IA) chemotherapy,
      comparing these data with clinical remission rates. METHODS: Included in the
      study were 61 patients (mean age 59.3 years; 47 men) with histologically proven
      small carcinoma of the oral cavity or the oropharynx (local tumor stages T1/2).
      Patients received IA chemotherapy with high-dose cisplatin as part of a
      multimodal therapeutic regimen and underwent both clinical and radiological
      examination before and 4 weeks after local chemotherapy. RESULTS: Clinical
      evaluation of tumor response was possible in all patients (61/61). Radiological
      assessment of tumor volume was feasible in 42 of 61 patients (69%), but failed in
      19 (31%) due to the absence of deep tumoral spread, lack of contrast enhancement
      or severe dental artifacts. Patients in whom evaluation was possible according to
      volumetric and clinical criteria revealed comparable remission rates: overall
      response 54.8% versus 52.4%, stable disease 40.4% versus 47.6%, and tumor
      progression 4.8% versus 0.0%. CONCLUSION: Because volume calculation was not
      feasible in approximately one-third of the patients, it cannot be recommended as
      a reliable indicator for treatment response in patients with small carcinoma of
      the oral cavity.

PMID- 16609896
TI  - Transcranial color-coded sonography in head injury.

PMID- 16609897
TI  - The effect of surgeon volume and hospital characteristics on in-hospital outcome
      after ureteral reimplantation in children.
AB  - The aim of this study was to examine the association between surgeon and hospital
      characteristics on in-hospital outcome after ureteral reimplantation in children.
      Patients<18 years undergoing vesicoureteral reimplantation (n=3,109) were
      identified in Kids' Inpatient Database, an administrative database containing
      discharge records from 27 states during 2000 in the US. Based on patient volume
      in 2000, surgeons were designated as low volume (<11 procedures), medium volume
      (11-20 procedures) and high volume (>20 procedures) surgeons. Length of stay and
      hospital charges were analyzed using multivariate linear regression analysis. A
      significant association between shorter length of stay and higher surgeon volume
      (p=0.02) was observed that was independent of children's hospital status,
      hospital volume and other hospital characteristics. Length of stay was 20%
      shorter when the procedure was performed by the highest volume surgeons compared
      to when performed by the lowest. No significant effect of surgeon volume on
      hospital charges, however, was observed. Higher surgeon volume was associated
      with shorter length of stay but no difference in hospital charges among children
      undergoing vesicoureteral reimplantation.

PMID- 16609898
TI  - Simple placement of prosthetic testes in children.
AB  - Testicular prostheses are inserted for cosmetic reasons for absent testes or
      after an orchidectomy. Most complications related to testicular prostheses
      insertions are due to excessive tissue and prostheses handling. We describe a
      simple and reliable technique of insertion of testicular prostheses that provides
      a good cosmetic outcome and could potentially minimise complications.

PMID- 16609899
TI  - Splenoptosis complicated by a large splenic cyst: case report and discussion of
      combined management.
AB  - Splenoptosis is a rare condition in children. Its association with a cyst is
      rare. A case of splenoptosis complicated by a large cyst is reported. The child
      presented with features of intermittent abdominal pain, constipation and clinical
      examination revealed a mass apparently rising out of the pelvis. Ultrasound
      confirmed the mass as spleen with a 15 cm cyst in the lower pole. At surgery the
      cyst was marsupialised and splenopexy undertaken placing the cyst in a retro
      peritoneal pouch. This is only the second report of such a case in the English
      literature.

PMID- 16609900
TI  - [Light protection: principles of UV protection].
AB  - UV radiation is responsible for the induction of epithelial and melanocytic skin
      cancer, photoaging, and photodermatoses. UV protection is necessary to prevent
      damage caused by non-physiologic exposure. UV protection includes not only
      reduction of sun exposure but also use of sun protective filters, UV protective
      clothes, DNA repair enzymes, and antioxidant supplementation. Consumers are
      uncertain about the possibilities and limitations of commercial sun protection
      measures. Dermatologists must explain protective measures to the general public
      which continues to believe that UV-tanned skin is healthy. The sunscreen market
      is a highly competitive but lucrative market. The range of products with
      different designations and promises makes difficult for both consumers and
      dermatologists to determine what is sensible UV protection.

PMID- 16609901
TI  - Management of sepsis in neutropenia: guidelines of the infectious diseases
      working party (AGIHO) of the German Society of Hematology and Oncology (DGHO).
AB  - These guidelines from the infectious diseases working party (AGIHO) of the German
      Society of Hematology and Oncology (DGHO) give recommendations for the management
      of adults with neutropenia and the diagnosis of sepsis. The guidelines are
      written for clinicians and focus on pathophysiology, diagnosis, and treatment of
      sepsis. The manuscript contains evidence-based recommendations for the assessment
      of the quality and strength of the data.

PMID- 16609902
TI  - Delay discounting and the behavioural economics of cigarette purchases in
      smokers: the effects of nicotine deprivation.
AB  - RATIONALE: In smokers, nicotine deprivation may increase impulsive decision
      making and the demand for cigarettes. OBJECTIVES: To investigate the effects of
      acute nicotine deprivation on (a) the delay discounting of monetary and cigarette
      rewards, and (b) the behavioural economics of hypothetical cigarette purchases.
      MATERIALS AND METHODS: A repeated measures design was employed, with participants
      (daily cigarette smokers, N=30) repeating experimental tasks in two different
      sessions, once after at least 13 h of abstinence from smoking and once after ad
      lib smoking. Participants completed measures of cigarette craving, impulsivity,
      delay discounting and a behavioural economic simulation in which participants
      made hypothetical purchases of cigarettes and other commodities as the price of
      cigarettes was systematically varied. RESULTS: Participants showed more
      pronounced delay discounting of both cigarette and monetary rewards after
      abstinence compared to after ad lib smoking. In the behavioural economic
      simulation, nicotine deprivation had no influence on hypothetical cigarette
      purchases. However, spending on some commodities (alcohol, clothing, household
      goods, leisure activities and long-distance travel) was reduced as the price of
      cigarettes increased in order to fund increased spending on cigarettes, although
      the number of packs of cigarettes purchased actually decreased. CONCLUSIONS:
      Nicotine deprivation increases impulsive choices for both cigarette and monetary
      rewards in a delay-discounting task. Results from a behavioural economic
      simulation suggest that increases in the price of cigarettes may increase
      smokers' spending on cigarettes, while also reducing the number of cigarettes
      purchased.

PMID- 16609903
TI  - A decrease in the plasma DHEA to cortisol ratio during smoking abstinence may
      predict relapse: a preliminary study.
AB  - RATIONALE: Increases in depressive symptoms during smoking cessation have been
      associated with risk for relapse. Several studies have linked plasma levels of
      cortisol and dehydroepiandrosterone (DHEA) or DHEA-sulfate (DHEAS) to depressive
      symptoms. OBJECTIVES: To determine whether changes in plasma cortisol, DHEA, or
      DHEAS levels and emergence of depressive symptoms during smoking cessation are
      associated with smoking relapse. MATERIALS AND METHODS: Subjects were healthy non
      medicated men and women, aged 39+/-12 years, who smoked, on average, 22
      cigarettes per day. Depressive symptoms, smoking withdrawal symptoms, and plasma
      steroid levels were measured before and after 8 days of verified smoking
      abstinence. Relapse status at day 15 was then determined. RESULTS: In the full
      sample (n=63), there was a trend for changes in depressive symptoms to be
      associated with relapse. In the subset of 25 subjects with plasma neuroactive
      steroid data, there was a significant interaction between the change in the
      plasma DHEA/cortisol ratio from day 0 to day 8 and relapse status at day 15. This
      ratio was similar before abstinence, but lower at day 8 in relapsed, compared to
      abstinent, subjects. Changes in the DHEA/cortisol ratio tended to predict changes
      in depressive symptoms in the women only. CONCLUSION: A decrease in the plasma
      DHEA/cortisol ratio during 8 days of smoking abstinence was associated with
      relapse over the following week. Further research is needed to fully characterize
      sex-specific relationships between abstinence-induced changes in neuroactive
      steroid levels, depressive or withdrawal symptoms, and relapse. Such research may
      lead to new interventions for refractory smoking dependence.

PMID- 16609904
TI  - Remodeling of the vascular channels in retinal angiomatous proliferations treated
      with intravitreal triamcinolone acetonide and photodynamic therapy.
AB  - BACKGROUND: The objective was to describe the remodeling of the vascular channels
      in stage II retinal angiomatous proliferation (RAP) treated by intravitreal
      injections of triamcinolone acetonide (TA) and subsequent photodynamic therapy
      (PDT). METHODS: Stage II RAP secondary to age-related macular degeneration was
      documented by dynamic digital fluorescein and indocyanine green angiography in 3
      consecutive patients (3 eyes). All eyes were treated with intravitreal injection
      of TA (4 mg, 0.1 ml) followed by PDT 5-10 days later. RESULTS: Indocyanine green
      angiography (ICGA) revealed a complete remodeling of the vascular structure of
      the three RAPs after treatment. The feeding retinal artery, which shunted a major
      part of the blood flow from the original arteriole toward the intraretinal
      neovascular complex before treatment, regained a normal appearance after
      treatment. With RAP closure, the blood flow was again directed through the
      original retinal arteriole, and the connection to the RAP was no longer visible.
      CONCLUSIONS: Stage II RAPs are difficult lesions to treat. A real remodeling of
      the vascular lesion is achieved with the combined use of intravitreal TA and PDT.
      This finding corroborates the need for randomized clinical trials currently under
      way to evaluate this combination treatment in wet, age-related macular
      degeneration.

PMID- 16609905
TI  - The significance of lysosomal inclusions in Fabry disease.

PMID- 16609906
TI  - Carbonic anhydrase-related protein VIII increases invasiveness of non-small cell
      lung adenocarcinoma.
AB  - Carbonic anhydrase-related protein VIII (CA-RP VIII) is believed to be an
      oncofetal antigen and is overexpressed in colorectal and non-small cell lung
      cancer. However, the pathobiological properties of CA-RP VIII in lung cancer
      remain unclear. In the present study, we examined ultrastructural changes caused
      by exogenous CA-RP VIII expression in a well-differentiated lung adenocarcinoma
      cell line, PC-9. Many vacuoles lined by cilia, sometimes large vacuoles pushing
      the nuclei to one side, were found in the cytoplasm of CA-RP VIII-expressing PC-9
      cells, but not in control PC-9 cells. Moreover, signet-ring cells containing
      abundant intracytoplasmic mucin were often found among CA-RP VIII-expressing PC-9
      cells, but rarely among control PC-9 cells. We subsequently examined CA-RP VIII
      expression in atypical adenomatous hyperplasia and early-stage lung
      adenocarcinoma (Stage Ia). Significant expression of CA-RP VIII was observed in
      invasive lung adenocarcinoma but not in noninvasive adenocarcinoma.
      Interestingly, CA-RP VIII was strongly expressed in signet-ring cell cancer and
      invasive mucinous adenocarcinoma components. CA-RP VIII also appeared to enhance
      the invasiveness of PC-9 cells in Matrigel invasion assay. The present findings
      suggest that CA-RP VIII expression in lung adenocarcinoma is related to cancer
      cell invasion.

PMID- 16609907
TI  - Pathological function of prostaglandin E2 receptors in transitional cell
      carcinoma of the upper urinary tract.
AB  - The prostaglandin E2 receptor, EP4 receptor (EP4R), plays an important role in
      the development of transitional cell carcinoma of the upper urinary tract (TCC
      UUT). However, the clinical significance of other EP receptors (EP1R-3R) is not
      clear. Furthermore, the pathological function of EP receptors in such patients is
      not understood. In the present study, we examined the expression of EP1R-3R in
      101 TCC-UUT tissues by immunohistochemistry. Furthermore, we defined the
      relationship between cyclooxygenase (COX)-2 and EP receptor expression,
      proliferation index (PI), microvessel density (MVD), and expression of
      metalloproteinase-2 (MMP-2), urokinase-type plasminogen activator (uPA), and exon
      v6 containing CD44 isoform (CD44 v6) by multivariate analysis. The expression of
      EP1R, EP2R, and EP3R was positive in 20 (19.8%), 26 (25.7%), and 14 (13.9%) tumor
      samples, respectively. Expression of these receptors was not associated with
      pathological findings or survival. COX-2 and EP4R were independently associated
      with MVD and MMP-2, and uPA or PI and MMP-2, respectively. Other EP receptors
      were not influenced by any factors. Our results suggest that EP1R-3R play a
      minimal role in cancer progression in patients with TCC-UUT. On the other hand,
      EP4R regulates tumor progression via cancer cell proliferation and MMP-2,
      distinct from COX-2.

PMID- 16609908
TI  - Up-regulation of matrix metalloproteinase-2 and membrane-type 1-matrix
      metalloproteinase were coupled with that of type I procollagen in granulation
      tissue response after the onset of aortic dissection.
AB  - The pathophysiological significance of matrix metalloproteinases (MMPs) in aortic
      dissection remains poorly understood. The purpose of the present study is to
      clarify the significance of MMPs in aortic dissection. The activities and
      distributions of MMP-2, membrane-type 1-MMP (MT1-MMP), and MMP-9 were evaluated
      by gelatin zymography, immunohistochemistry, and in situ hybridization in 29
      patients and seven autopsy cases. To assess if these MMPs are related to a tissue
      remodeling process, we compared the expression of these MMPs with that of type I
      procollagen and platelet-derived growth factor receptor beta chain (PDGF Rbeta).
      Patients were divided into three groups based on histological findings: acute,
      intermediate, and healed groups. The most remarkable changes were observed in the
      intermediate group, in which MMP-2 activity peaked and tissue expression of mRNAs
      for MMP-2 and MT1-MMP were observed in spindle-shaped cells in the neointima,
      organizing thrombus, and the adventitia. These expression patterns were
      essentially coupled with those of type I procollagen mRNA and PDGF-Rbeta protein.
      The association of MMP-2, MT1-MMP, type I procollagen, and PDGF-Rbeta suggests
      that MMP-2 and MT1-MMP could be involved not only in the degradation of aortic
      tissue but also in tissue remodeling, which may be associated with the healing
      process.

PMID- 16609909
TI  - Coexistence of Epstein-Barr virus-associated gastric carcinoma with malignant
      lymphoma: report of two cases.
AB  - Epstein-Barr virus (EBV)-associated gastric carcinoma (EBV-GC) is not rare,
      accounting for 5 to 18% of all gastric carcinomas. Recently, we encountered two
      cases of EBV-GC of ordinary histopathological type coexistent with malignant
      lymphoma. One patient was a 71-year-old Japanese man who had two lesions, one in
      the cardia and the other in the antrum of the stomach. The former was EBV-GC
      without lymphoma, and antral one was EBV-GC with diffuse large B-cell lymphoma
      (DLBCL). The other patient was a 49-year-old Japanese man who had received
      chemotherapy for pelvic DLBCL 3 years earlier. He had EBV-GC with follicular
      lymphoma in the fundus of the stomach. In both cases, gastric carcinomas were
      positive for EBV-encoded small RNA by in situ hybridization, whereas the lymphoma
      cells, infiltrating nonneoplastic lymphocytes, and nonneoplastic epithelial cells
      were negative. The present cases suggest that focal immunosuppression by adjacent
      gastric lymphomas might be related to the alteration of the microenvironment and
      development of EBV-GC.

PMID- 16609911
TI  - Unusual ultrastructural features in microvillous inclusion disease: A report of
      two cases.
AB  - Microvillous Inclusion Disease (MID) is an inherited disorder characterized by
      intractable diarrhea in infancy. Ultrastructural detection of pathognomonic
      microvillous inclusions in the enterocytes is essential for diagnosis. The aim of
      this research is to contribute to the knowledge of MID studying enterocytes and
      goblet cells (gc). Samples of duodenal mucosa from two young infants with MID
      (aged 75 days and 3 months, respectively) were studied by light and electron
      microscopy. Detection in the intestinal villi of immature gc (with microvilli) in
      one of the cases led us to seek them in control samples. The total number of gc
      with microvilli (immature) and without microvilli (mature) were counted. In both
      MID specimens, light microscopy showed atrophy of villi and PAS-positive material
      in the enterocyte cytoplasm. The ultrastructure of villous enterocytes was
      characterized by brush-border abnormalities, microvillous inclusions, dense
      apical granules, and lysosomes. Intermediate structures between microvillous
      inclusions and lysosomes were also detected within a cell, as were rare
      microvilli on the lateral membrane of the enterocytes. In one MID specimen,
      immature gc were also identified in the absorptive compartment. Only mature gc
      were observed in the controls. The significance of the latter finding requires
      further studies.

PMID- 16609910
TI  - Cytokeratin 7/20 and mucin core protein expression in ulcerative colitis
      associated colorectal neoplasms.
AB  - Different histogenetic pathways have been suggested between ulcerative colitis
      (UC)-associated neoplasia and sporadic colorectal neoplasia. Little is known
      about the cytokeratin (CK) and mucin expression in UC-associated neoplasms. To
      clarify the characteristics of UC-associated colorectal carcinogenesis, we
      examined the immunohistochemical expression of CK7, CK20, MUC2, MUC5AC and MUC6
      in 90 colorectal neoplasms, including 22 UC-associated adenocarcinomas (colitic
      cancer; CC), ten high-grade dysplasias (HGD) in UC, nine low-grade dysplasias
      (LGD) in UC, 24 sporadic tubular adenomas (TA) and 25 adenocarcinomas (AC). CK7
      was positive in most of UC-associated neoplasms: 59% of CC cases, 80% of HGD and
      89% of LGD, respectively, whereas, in non-UC associated neoplasia, 21% of TA and
      12% of AC. The frequency of MUC6 expression in UC-associated neoplasia was 32% in
      CC, 30% in HGD and 44% in LGD, respectively, whereas, in non-UC associated
      neoplasia, 4.2% in TA and 0% in AC. MUC5AC expression in UC-associated neoplasia
      was detectable in 73% of CC, 90% of HGD and 89% of LGD, respectively; in non-UC
      associated neoplasia 67% in AC and 20% in TA. There were obvious differences in
      the expression of CK7 and MUC6 between UC-associated neoplasms and sporadic
      tumors. The incidence of MUC5AC expression in UC-associated neoplasms was also
      higher than sporadic tumors. These results suggest that gastric-type mucins play
      an important role in the initial step of CC-tumorigenesis, and CK7 and gastric
      type mucins may be useful in the differential diagnosis between UC-associated
      neoplasms and sporadic ones.

PMID- 16609912
TI  - Warthin's tumour.

PMID- 16609913
TI  - Human T-cell lymphotropic virus type I (HTLV-1) associated myelopathy and
      Sjogren's syndrome representing pulmonary nodular amyloidosis and multiple
      bullae: Report of an autopsy case.

PMID- 16609914
TI  - Immunoreactivity to molluskan neuropeptides in the central and stomatogastric
      nervous systems of the earthworm, Lumbricus terrestris L.
AB  - Polyclonal antisera against two related command neuropeptides (CNP2 and CNP4)
      described in neurons of the terrestrial snail Helix were used in a study of the
      nervous system of the earthworm Lumbricus. The CNP-like peptides belong to the
      same neuropeptide subfamily and bear a C-terminal signature sequence Tyr-Pro-Arg
      X. The distribution patterns of immunoreactive (IR) neurons were studied in the
      central nervous system (CNS), skin, and stomatogastric nervous system of the
      earthworm. IR neurons were found in all CNS ganglia, the patterns being similar
      for both antibodies used. Several clusters of IR cells were observed in the
      cerebral and subesophageal ganglia. In the ventral cord ganglia, the number of IR
      cells decreased in the rostro-caudal direction, and the IR cells sent their
      fibers mostly into the median fiber bundle. Segmental nerves contained no IR
      fibers. After injury of the worm body, the number of IR neurons in the CNS
      significantly increased. In the skin, IR sensory neurons were present in sensory
      buds. The stomatogastric ganglia only contained IR fibers. Numerous scattered IR
      neurons were found in the inner subepithelial layer of the esophagus and formed
      the enteric plexus in which the cell bodies displayed a segmentally repeated
      pattern. Possible involvement of CNP-like-IR neurons in central integratory
      processes, sensory processes, and the regulation of feeding is discussed.

PMID- 16609916
TI  - Apoptosis-inducing factor of a cytotoxic T cell line: involvement of a secretory
      phospholipase A2.
AB  - Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) kill target cells by
      the granule-exocytosis pathway and by the engagement of molecules belonging to
      the tumor necrosis factor family. The involvement of secretory phospholipase A(2)
      (sPLA(2)) in the cytotoxic process has been proposed in NK cells. However, its
      molecular identity and intracellular localization remain unknown, and its
      mechanism of action is poorly understood. Here, we have readdressed this issue by
      studying the cytotoxic activity of whole cell extracts of a CTL line. We observed
      that inactivation of the perforin-granzyme pathway at 37 degrees C in the
      presence of 1 mM Ca(2+) enhanced the ability of CTL extracts to induce apoptosis.
      This potentiation of cell death was Ca(2+)-dependent, thermo-resistant, and
      inhibited by 4-bromophenacyl bromide and scalaradial (two inhibitors of sPLA(2)).
      The involvement of an sPLA(2) was confirmed by blocking the pro-apoptotic
      activity of the Ca(2+)-treated cell extract with an anti-sPLA(2) polyclonal
      antibody. By cell fractionation assays, we showed that the pro-apoptotic sPLA(2)
      was localized in the cytoplasmic fraction but not in perforin-rich granules or
      plasma membrane fractions. Western blotting analysis revealed the presence of
      four distinct bands of 56, 29.5, 21, and 15 kDa. The highest molecular weight
      band was consistent with the expression of a group III sPLA2. Taken together,
      these data indicate that an apoptosis-inducing sPLA(2) is expressed in the
      cytosol of a CTL cell line and suggest that it plays an effector role in CTL
      mediated cytotoxicity.

PMID- 16609915
TI  - Expression of the cystine-glutamate exchanger (xc-) in retinal ganglion cells and
      regulation by nitric oxide and oxidative stress.
AB  - The cystine-glutamate exchanger, system x(c)(-), mediates the Na(+)-independent
      exchange of cystine into cells, coupled to the efflux of intracellular glutamate.
      System x(c)(-) plays a critical role in glutathione homeostasis. Early studies of
      brain suggested that system x(c)(-) was present primarily in astrocytes but not
      neurons. More recent work indicates that certain brain neurons have an active
      system x(c)(-). In the retina, system x(c)(-) has been demonstrated in Muller and
      retinal pigment epithelial cells. We have recently suggested that two protein
      components of system x(c)(-), xCT and 4F2hc, are present in ganglion cells of the
      intact retina. Here, we have used (1) molecular and immunohistochemical assays to
      determine whether system x(c)(-) is present in primary ganglion cells isolated
      from neonatal mouse retinas and (2) functional assays to determine whether its
      activity is regulated by oxidative stress in a retinal ganglion cell line (RGC
      5). Primary mouse ganglion cells and RGC-5 cells express xCT and 4F2hc. RGC-5
      cells take up [(3)H]glutamate in the absence of Na(+), and this uptake is blocked
      by known substrates of system x(c)(-) (glutamate, cysteine, cystine, quisqualic
      acid). Treatment of RGC-5 cells with NO and reactive oxygen species donors leads
      to increased activity of system x(c)(-) associated with an increase in the
      maximal velocity of the transporter with no significant change in the substrate
      affinity. This is the first report of system x(c)(-) in primary retinal ganglion
      cells and RGC-5 cells. Oxidative stress upregulates this transport system in RGC
      5 cells, and the process is associated with an increase in xCT mRNA and protein
      but no change in 4F2hc mRNA or protein.

PMID- 16609917
TI  - Extracellular matrix changes in knee joint cartilage following bone-active drug
      treatment.
AB  - Certain drugs or treatments that are known to affect bone quality or integrity
      might have side effects on the extracellular matrix of articular cartilage. We
      investigated the effects of vitamin D and calcium deficiency, estrogen
      deficiency, and hypercortisolism alone or in combination with bisphosphonates or
      sodium fluoride in an animal model, viz., the Gottingen miniature pig (n=29). The
      articular cartilage from knee joints was analyzed for its content of
      glycosaminoglycans (GAGs, as macromolecules responsible for the elasticity of
      articular cartilage) by a spectrometric method with dimethylene blue chloride. In
      cryo- or paraffin sections, alkaline phosphatase (AP, as an enzyme indicating
      mineralization or reorganization of articular cartilage matrix) was localized by
      enzyme histochemistry, and positive cells were counted, whereas differently
      sulfated GAGs were stained histochemically. A significant decrease in GAG content
      was measured in ovariectomized and long-term glucocorticoid-treated animals
      compared with untreated animals. In the glucocorticoid/sodium fluoride group,
      GAGs were significantly diminished, and significantly fewer AP-positive
      chondrocytes were counted compared with the control. GAG content was slightly
      higher, and significantly more AP-positive chondrocytes were counted in short
      term glucocorticoid-treated animals then in the control group. GAGs, as part of
      proteoglycans, are responsible for the water-storage capacity that gives
      articular cartilage its unique property of elasticity. Thus, ovariectomy and long
      term glucocorticoid therapy, especially when combined with sodium fluoride, have
      detrimental effects on this tissue.

PMID- 16609918
TI  - Differential expression of caveolin-3 in mouse smooth muscle cells in vivo.
AB  - Expression of caveolin-1 and -3 in mouse smooth muscle cells in vivo was examined
      by immunohistochemistry. Caveolin-1 was detected in almost all smooth muscles
      examined, except for the pupillary dilator muscle, whereas caveolin-3 was present
      only in smooth muscles of some specific tissues. In the eye, the pupillary
      sphincter muscle was intensely positive for caveolin-3, whereas the ciliary
      muscle and pupillary dilator muscle were negative. In the gastrointestinal tract,
      caveolin-3 was detected in the inner circular layer, but not in the outer
      longitudinal layer. Vascular smooth muscle cells of the resistance-sized artery
      in the uterus and corpus cavernosum were intensely positive for caveolin-3,
      whereas those of the aorta were only weakly positive and those of the vena cava
      were negative. Caveolin-3 was also detected in smooth muscle cells of the urinary
      bladder, ureter, prostatic vas deferens, and seminal vesicle. The different
      levels of caveolin-3 expression among various smooth muscle tissues were
      confirmed by Western blot analysis. Even within the same muscle, the relative
      expression levels of caveolin-1 and -3 were variable among neighboring cells,
      suggesting distinct fine regulation of expression of these two caveolins.
      Moreover, even in the same cell, caveolin-1 and -3 showed different
      distributions. These results indicate that the two caveolins form distinct
      caveolae in smooth muscles, and that caveolin-1 and -3 serve different functions.
      Their differential expression may therefore be related to the functional
      diversity of smooth muscles.

PMID- 16609919
TI  - Fixation methods can produce misleading artifacts in sperm cell ultrastructure of
      diploid and tetraploid Pacific oysters, Crassostrea gigas.
AB  - Spermatozoa from diploid and tetraploid Pacific oysters (Crassostrea gigas) were
      examined after anisotonic fixation. Morphological anomalies, such as membrane
      rupture, detached tails, and the formation of tail vesicles (typically associated
      with damage attributable to procedures such as cryopreservation) were observed;
      the Mantel-Haenszel Chi-square test indicated a strong association between the
      anomalies and fixative osmolality (P<0.001). The present study also indicated
      that media in a range of 800 to 1,086 mOsm/kg could be assumed to be functionally
      isotonic to Pacific oysters, and osmolalities below or above this caused severe
      cell damage. For example, the maximum volume of flagella obtained after hypotonic
      fixation was approximately twice the volume of the flagella in isotonic fixation.
      Sperm cell flagellar volumes after hypertonic fixation (1,110 mOsm/kg) were 32%
      smaller than those in isotonic fixation, and sperm heads were 25% smaller.
      Although the damage associated with anisotonic fixation was evident in all parts
      of the sperm cells, the most vulnerable locations were the plasma membrane and
      flagellum motor apparatus. The formation of tail vesicles after hypotonic
      fixation was also examined. Because of water uptake, oyster sperm became swollen
      in hypotonic fixative, and bending or coiling of the axoneme within the tail
      vesicles led to the appearance of multiple axonemal structures in cross sections
      when observed by transmission electron microscopy. This phenomenon might be
      generally misinterpreted as the presence of double tails. This and other fixation
      artifacts can lead to the misinterpretation of damage caused by cryopreservation
      in ultrastructure studies of sperm of aquatic species, especially those in marine
      species.

PMID- 16609920
TI  - Cytomorphological study on human submandibular gland following treatment with
      secretagogue drugs.
AB  - Using specimens of human submandibular glands, we have investigated in vitro the
      morphological modifications induced by clozapine, a dibenzodiazepine derivative
      that is used in psychotic patients and that provokes hypersalivation, a side
      effect of therapy. The effects of the drug, used alone or in combination with
      carbachol, have been compared with those observed after treatment with drugs
      acting on specific receptors. To quantify the response to stimulation, we have
      calculated (with statistical methods) the number of microvilli and microbuds
      (corresponding to pits seen in images obtained by transmission electron
      microscopy) per square micrometre of the cytoplasmic surface of the intercellular
      canaliculi luminal membrane in images obtained by high-resolution scanning
      electron microscopy. Clozapine, when directly acting on human submandibular
      specimens, induces a small secretory response in serous cells; this is partially
      decreased by muscarinic and adrenergic antagonists and by combined incubation
      with carbachol, thus confirming its behaviour as a partial agonist to muscarinic
      receptors. We also suggests that the drug acts on the nerve terminals contained
      within the glandular specimens.

PMID- 16609922
TI  - [Free will: scientific and philosophical issues].

PMID- 16609923
TI  - [Diagnostics and treatment of bulimic eating disorders].

PMID- 16609924
TI  - Intermediary metabolism and life-history trade-offs: differential metabolism of
      amino acids underlies the dispersal-reproduction trade-off in a wing-polymorphic
      cricket.
AB  - Although the differential flow of metabolites through alternate pathways of
      intermediary metabolism is thought to be an important functional cause of life
      history trade-offs, this phenomenon remains understudied. Using a radiolabeled
      amino acid, we quantified genetic differences in in vivo amino acid metabolism
      between morphs of the wing-polymorphic cricket Gryllus firmus that trade off
      early-age reproduction and dispersal capability. Lines selected for the flight
      capable morph, which delays reproduction, oxidized a greater proportion of
      radiolabeled glycine and converted a greater amount into somatic lipid, mainly
      triglyceride (flight fuel). By contrast, lines selected for the flightless,
      reproductive morph converted a substantially greater proportion of glycine into
      ovarian protein. Compensatory interactions between amino acid and lipid
      metabolism make up a key aspect of specialization for dispersal versus
      reproduction in G. firmus: increased oxidation of amino acids by the flight
      capable morph spares fatty acid for enhanced conversion into triglyceride flight
      fuel. By contrast, increased oxidation of fatty acid by the flightless morph
      spares amino acids for enhanced biosynthesis of ovarian protein. Studies of amino
      acid and lipid metabolism in G. firmus currently represent the most detailed
      analyses of genetic modifications of intermediary metabolism that underlie a
      functionally important life-history trade-off found in natural populations.

PMID- 16609925
TI  - No evidence of current sexual selection on sexually dimorphic traits in a bird
      with high variance in mating success.
AB  - Sexual dimorphism, particularly in ornamental traits, is likely to have arisen by
      sexual selection. Most empirical and theoretical studies of sexual dimorphism
      assume that ongoing sexual selection also maintains the dimorphism. Over four
      seasons, I measured the sexual selection acting on three sexually dimorphic
      attributes (epaulet size, body size, and the blackness of the body plumage) of
      male red-winged blackbirds and found no consistent directional or stabilizing
      selection on any of them. Correlational selection was also negligible. I used
      path analysis to explore potential relationships in more detail but found no
      direct or indirect effects of male traits on either within- or extrapair success.
      Males who were resident on the marsh for more years had higher within-pair
      success, primarily because they spent more of the season on their territory.
      Experimental manipulations of epaulet size and color and the extent of nonblack
      feathers in the black body plumage had no detectable effect on the number of
      within-pair mates, paternity, or the number of extrapair offspring sired in
      nearby territories. These results combine with data from other studies of red
      winged blackbirds to suggest that, despite high variation in male mating success
      and hence a strong opportunity for sexual selection, several morphological
      attributes that differ between the sexes and vary among males are not under
      current sexual selection. The possible explanations for why add complexity to our
      understanding of how sexual selection operates.

PMID- 16609926
TI  - Peritoneal B-2 cells comprise a distinct B-2 cell population with B-1b-like
      characteristics.
AB  - B-1 and B-2 cells are lymphocyte populations that differ in development, surface
      marker expression, tissue localization, and function. Though mainly found in the
      spleen, lymph nodes, and circulation of mice, small numbers of B-2 cells are
      found in the peritoneal cavity, a site predominantly populated by B-1 cells.
      Here, we characterized peritoneal B-2 cells, and determined their relationship to
      B-1 cells. We found that peritoneal B-2 cells appear to be intermediate between
      splenic B-2 and peritoneal B-1 cells in terms of surface marker expression of
      B220, CD80, and CD43, expression of several marker genes, and in vitro viability
      and IgM secretion. Adoptive transfer of peritoneal B-2 cells into severe combined
      immunodeficiency mice resulted in the acquisition of a phenotype reminiscent of B
      1b cells, as shown by up-regulation of Mac-1 and CD43, and down-regulation of
      CD23. Moreover, adoptively transferred peritoneal B-2 cells recapitulated B-1
      cell function by producing natural IgM in recipient mice. These data suggest that
      peritoneal B-2 cells express some characteristics of B-1b cells and that this
      similarity increases with additional time in the peritoneal cavity.

PMID- 16609927
TI  - Differential involvement of TLR2 and TLR4 in host survival during pulmonary
      infection with Chlamydia pneumoniae.
AB  - The relevance of TLR2 and TLR4 for recognizing Chlamydia pneumoniae in vivo
      during pulmonary infection and to survive the infection was explored. We found
      that early immune responses triggered by C. pneumoniae partially depended on
      TLR2, but not on TLR4. The chemokines MIP-2 and MIP-1alpha were not induced,
      while IL-12p40 levels were higher in TLR2(-/-) mice compared to wild-type mice.
      Secretion of TNF, keratinocyte-derived chemokine and monocyte chemoattractant
      protein-1 was attenuated in TLR2(-/-) mice, while IFN-gamma was increased as in
      wild-type mice. The pulmonary cyto- and chemokine response of TLR2(-/-) x
      TLR4(d/d) was similar to TLR2(-/-) mice. TLR2(-/-) and TLR2(-/-) x TLR4(d/d) mice
      also attracted fewer polymorphonuclear neutrophils into the lung, while TLR4(d/d)
      mice recruited them. Attenuated recruitment of polymorphonuclear neutrophils
      correlated with reduced weight loss in TLR2(-/-) and TLR2(-/-) x TLR4(d/d) mice
      and a lower chlamydial burden 3 days post infection. At 9 days post infection,
      TLR2(-/-) and TLR2(-/-) x TLR4(d/d) mice produced cyto- and chemokines as
      efficiently as wild-type mice, indicating that the involvement of TLR in
      inflammation varies over time. All TLR2(-/-) x TLR4(d/d) mice succumbed to the
      infection, while about 50% of TLR2(-/-) mice died. Taken together, the function
      of TLR2 and TLR4 is required to survive pulmonary infection with C. pneumoniae.

PMID- 16609928
TI  - Single-stranded small interfering RNA are more immunostimulatory than their
      double-stranded counterparts: a central role for 2'-hydroxyl uridines in immune
      responses.
AB  - It has recently become apparent that certain small interfering RNA (siRNA)
      sequences stimulate the innate immunity through endosomal Toll-like receptors
      (TLR), particularly TLR7 and TLR8. However, it remains unclear whether siRNA
      duplexes act as specific ligands for these receptors. To address this question
      and to overcome the problem of immune activation by siRNA, several RNA sequences
      were chemically synthesized and their effects were investigated. Results indicate
      that human peripheral blood mononuclear cells (PBMC) recognize and respond to a
      large number of sense or antisense single-stranded (ss) siRNA. In most cases
      immunostimulatory RNA motifs are more effectively recognized by innate immunity
      in the context of ss siRNA as compared to siRNA duplexes. Novel immunostimulatory
      RNA motifs were identified and their replacement with adenosines abrogated immune
      activation. Most notably, replacement of the 2'-hydroxyl uridines with either 2'
      fluoro, 2'-deoxy or 2'-O-methyl uridines abrogated immune activation. Thus,
      immune recognition of RNA by TLR can be evaded by 2'-ribose modifications of only
      uridines. Collectively, the data should facilitate the development of siRNA
      therapeutics and expand the understanding of how RNA is sensed by innate
      immunity.

PMID- 16609929
TI  - Special issue celebrating the 65th birthday of Professor Pier Giorgio Righetti.

PMID- 16609930
TI  - Universal interpolating function for the dispersion coefficient of DNA fragments
      in sieving matrices.
AB  - The separation of DNA fragments by (slab or capillary) gel electrophoresis has
      been studied extensively. To characterize the separation achieved by such
      systems, one needs to understand the impact (and their dependency upon the
      experimental quantities) of two physical parameters: the electrophoretic mobility
      mu and the diffusion coefficient D. Three different regimes have been shown to
      exist for both mu and D: the Ogston regime, the reptation regime and the
      reptation with orientation regime (note that separation is only possible for the
      first two regimes). In the small electric field limit, both mu and D are
      apparently well described by theories for all three regimes. Unfortunately this
      results in disjointed scaling laws and no theory-based general equations can
      apply to all regimes. Recently, an empirical interpolating formula has been
      proposed that adequately fits the low electric field mobility mu of dsDNA
      fragments across all three regimes and is compatible with accepted theories. In
      this article we review and clarify the current state of knowledge regarding the
      size dependence of the mobility and the diffusion coefficient and propose an
      interpolating formula for molecular size dependence of the low field diffusion
      coefficient D. With formulas for both the mobility and the diffusion coefficient
      as a function of the experimental conditions one could, in principle, optimize
      any gel/polymer matrix-based electrophoresis system for a wide range of DNA
      molecular sizes.

PMID- 16609931
TI  - Effect of organic cosolvents on the free solution mobility of curved and normal
      DNA molecules.
AB  - The free solution mobilities of curved and normal 199-bp DNA fragments have been
      measured in buffer solutions containing various quantities of the organic
      cosolvents methanol, ethanol, 2-propanol, 2-methyl-2,4-pentanediol (MPD),
      ethylene glycol, and ACN, using CE. The curved fragment, taken from the VP1 gene
      of SV40, contains five unevenly spaced A- and T-tracts in a centrally located
      "curvature module"; the A- and T-tracts have been mutated to other sequences in
      the normal 199-bp fragment. The free solution mobility of the curved 199-bp
      fragment is significantly lower than that of its normal counterpart in aqueous
      solutions [Stellwagen, E., Lu, Y. J., Stellwagen, N. C., Nucleic Acids Res. 2005,
      33, 4425-4432]. The mobilities of both the curved and normal fragments decrease
      with increasing cosolvent concentration, due to the effect of the cosolvent on
      the viscosity and dielectric constant of the solution. The mobility differences
      between the curved and normal 199-bp fragments and the mobility ratios decrease
      approximately linearly with the increasing mole fraction of cosolvent in the
      solution. Hence, MPD and other organic cosolvents affect DNA electrophoretic
      mobility by a common mechanism, most likely the preferential hydration of the DNA
      surface that occurs in aqueous cosolvents. The gradual loss of the anomalously
      slow mobility of the curved 199-bp fragment with increasing cosolvent
      concentration, combined with other data in the literature, suggests that
      preferential hydration gradually widens the narrow A-tract minor groove,
      releasing site-bound counterions in the minor groove and shifting the
      conformation toward that of normal DNA.

PMID- 16609932
TI  - Role of chemical structure in stereoselective recognition of beta-blockers and H1
      antihistamines by human serum transferrin in capillary zone electrophoresis.
AB  - Studies on chiral resolution of beta-blocker and H1-antihistamine drugs by CZE
      using human serum transferrin are described. The drugs with different structures
      passed a pseudostationary protein zone in a coated capillary applying the partial
      filling method for the chiral separation. In this study we screened 15 compounds;
      most of them showed longer migration time, indicating an interaction with
      transferrin. Stereoselective interaction was observed only for five beta-blockers
      (celiprolol, talinolol, mepindolol, bopindolol, and oxprenolol) and for one H1
      antihistamine (brompheniramine). The most important finding was that very small
      differences in the chemical structure of the drug resulted in significant changes
      in the stereoselective recognition. Resolution of mepindolol enantiomers was
      observed showing the essential role of one methyl group compared to pindolol,
      which is not resolved by transferrin. Bopindolol, also a derivative of pindolol
      having bigger difference in the structure, showed more experienced separation.
      The very slight difference between alprenolol and oxprenolol was also revealed
      with these methods, since only oxprenolol enantiomers, having an extra oxygen in
      the structure, are resolved. Determining the migration order of the eutomers and
      distomers (chlorpheniramine, brompheniramine) we can deduct conclusions about the
      role of serum proteins in the delivery of drugs within the body.

PMID- 16609933
TI  - Capillary electrophoretic investigation of the enantioselective metabolism of
      propafenone by human cytochrome P-450 SUPERSOMES: Evidence for atypical kinetics
      by CYP2D6 and CYP3A4.
AB  - An enantioselective CE method was used to identify the ability of CYP450 enzymes
      and their stereoselectivity in catalyzing the transformation of propafenone (PPF)
      to 5-hydroxy-propafenone (5OH-PPF) and N-despropyl-propafenone (NOR-PPF). Using
      in vitro incubations with single CYP450 enzymes (SUPERSOMES), 5OH-PPF is shown to
      be selectively produced by CYP2D6 and N-dealkylation is demonstrated to be
      mediated by CYP2D6, CYP3A4, CYP1A2, and CYP1A1. For the elucidation of kinetic
      aspects of the metabolism with CYP2D6 and CYP3A4, incubations with individual PPF
      enantiomers and racemic PPF were investigated. With the exception of the
      dealkylation in presence of R-PPF only, which can be described by the Michaelis
      Menten model, all CYP2D6-induced reactions were found to follow autoactivation
      kinetics. For CYP3A4, all NOR-PPF enantiomer formation rates as function of PPF
      enantiomer concentration were determined to follow substrate inhibition kinetics.
      The formation of NOR-PPF by the different enzymes is stereoselective and is
      reduced significantly when racemic PPF is incubated. Clearance values obtained
      for CYP3A4 dealkylation are stereoselective whereas those of CYP2D6 hydroxylation
      are not. This paper reports the first investigation of the PPF hydroxylation and
      dealkylation kinetics by the CYP2D6 enzyme and represents the first report in
      which enantioselective CE data provide the complete in vitro kinetics of
      metabolic steps of a drug.

PMID- 16609934
TI  - The human heart proteome: Two-dimensional maps using narrow-range immobilised pH
      gradients.
AB  - The analysis of complex proteomes is undertaken using a variety of techniques and
      technologies such as 2-DE, surface-enhanced laser desorption ionisation, and
      various types of MS. In order to overcome the complexities of protein expression
      in discrete proteomes, sample fractionation has become an important aspect of
      proteomic experiments. The use of narrow-range IPGs (nrIPGs) is of special
      importance using the 2-DE proteomics workflow, since an enhanced visualisation of
      a given proteome is achieved through an improved physical separation and
      resolution of proteins. The work described in this paper presents a series of
      protein maps of the human heart left ventricle proteome that have been generated
      using nrIPGs for the first, IEF, dimension of 2-DE. A total of 374 gel spots were
      excised from seven different pH gradients, covering the range pH 3-10, giving
      rise to a total of 388 identifications from 110 unique proteins. Using Gene
      Ontologies (GOs), the identified proteins were found to be associated with 97
      types of GO Process, 144 types of GO Function, and 54 types of GO Component. It
      is hoped that the maps presented in this paper will be of use to other
      researchers for reference purposes.

PMID- 16609935
TI  - Proteomics study of anthrax lethal toxin-treated murine macrophages.
AB  - The anthrax lethal toxin (LeTx) is composed of two proteins, protective antigen
      and lethal factor, which bind and enter the cell through a host receptor termed
      the anthrax toxin receptor (ATR). In the cell, LeTx targets p38, part of the MAP
      kinase signaling pathway. The toxin appears to initiate an apoptotic pathway in
      infected cells, indicating additional downstream targets of the toxin. We have
      applied a proteomics approach to investigate these downstream targets and the
      affected processes. In this study we have used an improved strategy for
      fractionation based on protein pI, off-gel electrophoresis, employed in
      conjunction with relative quantitation using the mass labeling approach. In our
      survey, 67 proteins were observed and quantified from the cytosol of RAW 264.7
      cells with respect to control versus toxin-treated cells. Many of these proteins
      are involved in the oxidative stress response, as well as apoptosis, and thus
      likely to be relevant to the effects of anthrax in infected cells. Our results
      indicate that the tumor necrosis factor-alpha-mediated pathway is compromised in
      intoxicated cells. The knowledge of such changes and the pathways leading to the
      changes should be of great value in understanding and combating this disease.

PMID- 16609936
TI  - Microscale analysis of proteins in inner ear tissues and fluids with emphasis on
      endolymphatic sac, otoconia, and organ of Corti.
AB  - Here we describe preparatory techniques adapted for the study of proteins of
      inner ear tissues and fluids that have allowed us to apply state-of-the-art
      analytical techniques in spite of the minute size and anatomical complexities of
      this organ. Illustrative examples address unresolved issues of functional and
      clinical significance. First, we demonstrate how quick-freezing and freeze drying
      prevents artifacts that arise from sampling endolymphatic sac (ES) content in the
      liquid state. This set the stage for the generation of the first protein profile
      of the ES. Identification of crucial proteins will help elucidate mechanisms of
      endolymph volume regulation and pathogenesis of Meniere's disease. Second, we
      show how a unique situation allowed identification of otoconial proteins by mass
      spectrometric analysis without prior separation and we discuss possible roles for
      these minor otoconins in otoconial development and prevention of degenerative
      diseases that affect balance. Finally, we demonstrate techniques for the precise
      dissection of organ of Corti and its substructures, while preserving their near
      normal chemical state. We extended an earlier study in which we identified a
      novel calcium-binding protein by IEF, oncomodulin, localized in the outer hair
      cells and show here the applicability of prefractionation for the screening of
      calcium-binding proteins of organ of Corti. These studies demonstrate how
      advanced preparatory and analytical techniques can be applied to studies of the
      inner ear.

PMID- 16609937
TI  - Improved 2-DE of microorganisms after acidic extraction.
AB  - 2-DE separations of protein extracts sometimes have problems with poor resolution
      and streaking. This problem is particularly apparent with microorganisms, most
      notably those with a large cell wall. Here we describe a novel, rapid protocol
      for the extraction of microorganisms in acidic conditions, leading to increased
      resolution and 2-D gel quality. The efficiency of the protocol is demonstrated
      with extracts of bacteria, Escherichia coli and Bacillus subtilis; fungus,
      Trichoderma harzianum and yeast, Saccharomyces cerevisiae. We also demonstrate
      using a membrane centrifugal filtration, that large acidic molecules in excess of
      100 kDa, probably including cell wall material, are responsible for the
      separation difficulties. A range of acidic extraction conditions were
      investigated, and it was found that optimal extraction is achieved using an
      extraction solution acidified to pH 3 by 80 mM citric acid. These findings have
      significant implications for the proteomic study of many medically,
      agriculturally and environmentally significant microorganisms, as the cell walls
      of these organisms are often considerably more complex than many commonly studied
      laboratory strains.

PMID- 16609938
TI  - Increased expression and phosphorylation of liver glutamine synthetase in well
      differentiated hepatocellular carcinoma tissues from patients infected with
      hepatitis C virus.
AB  - Hepatocellular carcinoma (HCC) is one of the most common fatal cancers, and
      chronic infection with hepatitis C virus (HCV) is thought to be one of the main
      causes in Japan. To identify diagnostic or therapeutic biomarkers for HCC
      associated with HCV (HCV-HCC), we tried to elucidate the factors related to the
      products from cancerous tissues of HCV-infected patients. From proteomic
      differential display analysis of liver tissue samples from HCV-HCC cancerous
      tissues and corresponding non-cancerous tissues from patients, three protein
      spots of the same molecular mass (42 kDa), whose expression increased in well
      differentiated cancerous tissues, were detected. Although their pI were
      different, they were identified as glutamine synthetase (GS) by PMF with MALDI
      TOF MS and by Western blotting using anti-GS specific mAb. Immunohistochemical
      analysis showed that tumor tissue consists of two parts, GS-positive cell and GS
      negative cell regions, suggesting that GS-producing cells grew in the tumor
      tissue as a nodule in nodules. The tryptic peptides of the most acidic GS isoform
      lost the signal of 899.5 Da, corresponding a peptide of SASIRIPR, and gained a
      signal of 1059.5 Da, which was submitted to PSD analysis. PSD analysis showed the
      neutral loss by elimination of two phosphate groups, supposed to be on serine
      residues of the 899.5-Da peptide, from serine 320 to arginine 327 in GS. PMF
      followed by PSD analysis is thought to be useful for the determination of
      phosphorylation sites of proteins showing molecular heterogeneity.

PMID- 16609939
TI  - Proteomic analysis of macrophages stimulated by lipopolysaccharide:
      Lipopolysaccharide inhibits the cleavage of nucleophosmin.
AB  - Lipopolysaccharide (LPS) is a complex glycolipid composed of a hydrophilic
      polysaccharide and a hydrophobic domain that is responsible for the biological
      activity of LPS. There are many reports about LPS stimulation, and many activated
      proteins have been detected after LPS stimulation in various cell types.
      Furthermore, most of the LPS signaling pathways are clear. However, we were
      interested in examining the changes of LPS-induced total cytosolic proteins
      expression and the LPS signaling pathway by the proteomics technique during LPS
      induced macrophage activation. Our study employed two-dimensional gel
      electrophoresis and mass spectrometry to analyze the proteins involved in LPS
      induced activation in RAW 264.7 cells. We found 11 protein spots whose expression
      was different between untreated cells and LPS-treated cells. Ten protein spots
      were identified, seven of which, tubulin beta-4 chain (49.6 kDa, pI 4.78),
      nucleophosmin (32.6 kDa, pI 4.62, two spots), 40S ribosomal protein SA (P40)
      (32.7 kDa, pI 4.74), transforming protein RhoA (21.8 kDa, pI 5.83), nucleolin
      (76.6 kDa, pI 4.69), and T-complex protein 1 zeta subunit (58 kDa, pI 6.63) were
      down-regulated, and three of which, nucleophosmin (32.6 kDa, pI 4.62, two spots)
      and proteosome subunit alpha type-1 (29.5 kDa, pI 6.00), were up-regulated. The
      suppression of the proteolytic degradation of nucleophosmin was associated with
      LPS-induced RAW 264.7 cell activation. Cleaved caspase-3 decreased, thus it might
      be involved in proteolysis of nucleophosmin in LPS-induced macrophage activation.
      Our study also demonstrated that there was no change of the expression of
      nucleophosmin at the mRNA level.

PMID- 16609940
TI  - Protein expression dynamics during replicative senescence of endothelial cells
      studied by 2-D difference in-gel electrophoresis.
AB  - Endothelial senescence contributes to endothelium dysfunctionality and is thereby
      linked to vascular aging. A dynamic proteomic study on human umbilical vein
      endothelial cells, isolated from three umbilical cords, was performed. The cells
      were cultured towards replicative senescence and whole cell lysates were
      subjected to 2-D difference gel electrophoresis (DIGE). Despite the biological
      variability of the three independent isolations, a set of proteins was found that
      showed senescence-dependent expression patterns in all isolations. We focused on
      those proteins that showed significant changes, with a paired analysis of
      variance (RM-ANOVA) p-value of < or =0.05. Thirty-five proteins were identified
      with LC-Fourier transform MS, and functional annotation revealed that endothelial
      replicative senescence is accompanied by increased cellular stress, protein
      biosynthesis and reduction in DNA repair and maintenance. Nuclear integrity
      becomes affected and cytoskeletal structure is also changed. Such important
      changes in the cell infrastructure might accelerate endothelium dysfunctionality.
      This study provides biological information that will initiate studies to further
      unravel endothelial senescence and gain more knowledge about the consequences of
      this process in the in vivo situation.

PMID- 16609946
TI  - Chemotherapy for myeloid malignancy in children with Fanconi anemia.
AB  - BACKGROUND: Children with Fanconi anemia (FA) have a markedly increased risk of
      developing myeloid malignancies. Historically, patients with FA and myeloid
      malignancy have extremely poor outcomes. There are currently no clinical trials
      or case series addressing the use of chemotherapy for children with FA, except in
      the context of preparative regimens for stem cell transplantation (SCT). In this
      report we describe the toxicity of a chemotherapy approach for patients with FA
      and myeloid malignancy to achieve cytoreduction prior to SCT. PATIENTS AND
      METHODS: Four patients with FA and myelodysplastic syndrome (MDS) or acute
      myeloid leukemia (AML) were treated with chemotherapy (fludarabine 30 mg/m(2) and
      cytosine arabinoside 300 mg/m(2) each on days 2-4 and granulocyte-colony
      stimulating factor (G-CSF) 5 microg/kg on days 1-5), termed reduced intensity
      FLAG prior to SCT. RESULTS: The chemotherapy was well tolerated with expected
      hematologic toxicity and no measurable toxicity in other organs. Two of the three
      patients with AML cleared blasts from their bone marrow. Reduction in marrow
      cellularity was also achieved in one patient with hypercellular MDS. CONCLUSION:
      These data indicate that children with FA and myeloid malignancy can tolerate
      chemotherapy and achieve clearance of disease. It remains unclear whether pre-SCT
      chemotherapy improves currently poor survival rates for SCT in FA patients with
      myeloid malignancies and further studies are needed to determine if there is a
      clinical role for this strategy.

PMID- 16609945
TI  - Role of chemotherapy resistance genes in outcome of neuroblastoma.
AB  - BACKGROUND: Neuroblastoma is a heterogeneous pediatric disease. Most patients
      with localized disease usually have a favorable prognosis, but patients with
      advanced disease have a poor prognosis despite combination chemotherapy.
      Treatment failure may be attributable to resistance to cytotoxic drugs.
      PROCEDURE: Using quantitative RT-PCR, we investigated the clinical significance
      of the level of mRNA expression of multidrug resistance genes (MDR1, MRP1, MRP5,
      LRP) in a series of 29 advanced neuroblastoma samples. RESULTS: At the end of
      induction chemotherapy, 48% of patients achieved a clinical complete response,
      28% achieved a partial response or stable disease, and 24% presented progressive
      disease. MDR1 mRNA overexpression (i.e., mRNA level >2 copies of MDR1 gene) was
      observed in 74% of samples, and MRP1, MRP5, LRP overexpression was observed less
      frequently (30, 33, and 33% of samples, respectively). None of these parameters
      were predictive of response, relapse, or survival. However, clinical response to
      treatment was highly predictive of relapse-free survival and overall survival.
      CONCLUSIONS: High expression of these multidrug resistance genes in advanced
      neuroblastoma is not the main parameter of response to cytotoxic drugs; clinical
      response to treatment remains the most important parameter in predicting the
      prognosis of patients with advanced neuroblastoma, until other relevant
      laboratory parameters have been identified.

PMID- 16609947
TI  - Effect of dialysis on all trans retinoic acid levels in a child with acute
      promyelocytic leukemia and renal failure.
AB  - All trans retinoic acid (ATRA) combined with chemotherapy has become the mainstay
      of treatment for patients with acute promyelocytic leukemia (APL). Renal
      dysfunction (RD) is commonly seen in patients with APL. We describe a patient
      with APL and multi-organ failure, who was on chronic veno-venous hemofiltration
      followed by hemodialysis (HD) and later peritoneal dialysis (PD), who received
      ATRA. ATRA levels were assessed as the body clearance of ATRA in children on HD
      and/or PD was unknown. Neither HD nor PD significantly affected ATRA levels,
      suggesting that dose modifications of ATRA may not be necessary for children with
      these forms of renal replacement therapy.

PMID- 16609948
TI  - Rhabdoid tumors in a shared parental environment.

PMID- 16609949
TI  - Vincristine-induced bilateral vocal cord paralysis in children.

PMID- 16609950
TI  - Long-term remission of children with relapsed and secondary anaplastic large cell
      non-Hodgkin lymphoma (ALCL) following treatment with pulsed dexamethasone and low
      dose etoposide.
AB  - Anaplastic large cell lymphoma (ALCL) accounts for approximately 15% of childhood
      NHL. Relapsed ALCL represents a formidable challenge because outcome is poor
      despite the use of high-dose chemotherapy regimens. We report two patients with
      relapsed T-type and 0-type ALCL who achieved long-term 3rd and 4th remissions
      with 4-weekly oral dexamethasone (DEX) and etoposide pulses for 2 years. This
      regimen also induced and maintained remission in a third patient with Nijmegen
      breakage syndrome (NBS) with secondary T-type ALCL. These patients demonstrate
      that low-intensity oral chemotherapy can induce long-term remissions and offer a
      curative perspective in refractory, relapsed and secondary ALCL.

PMID- 16609951
TI  - Life-threatening hemangiomatosis of the liver in an infant: multimodal therapy
      including cyclophosphamide and secondary acute myeloid leukemia.

PMID- 16609953
TI  - Remote ischaemic preconditioning of the hind limb reduces experimental liver warm
      ischaemia-reperfusion injury.
AB  - BACKGROUND: Direct ischaemic preconditioning of the liver reduces ischaemia
      reperfusion injury (IRI). Remote ischaemic preconditioning (RIPC) of a limb has
      been shown to reduce IRI to the heart. This study determined the effect of brief
      remote ischaemia to the limb in reducing early liver warm IRI. METHODS: Twenty
      eight male rabbits were allocated to four groups: sham operated, RIPC alone, IRI
      alone, and RIPC plus IRI. RIPC was induced in the leg with a tourniquet, before
      liver IRI, by three alternate cycles of 10 min ischaemia followed by 10 min
      reperfusion. Liver IRI was produced by total inflow occlusion for 25 min. Markers
      of liver injury and systemic and hepatic haemodynamics were measured for 2 h
      after reperfusion. RESULTS: At 2 h, IRI alone was associated with increased serum
      levels of aminotransferases, and reduced mean arterial blood pressure, hepatic
      blood flow and peripheral oxygen saturation. There was significant improvement in
      these variables in animals that had RIPC before liver IRI, and hepatic venous
      nitrate/nitrite levels were also significantly higher. CONCLUSION: In this
      experimental model RIPC appeared to reduce liver IRI.

PMID- 16609952
TI  - MGMT promoter methylation correlates with survival benefit and sensitivity to
      temozolomide in pediatric glioblastoma.
AB  - BACKGROUND: Methylation of the DNA-repair gene O6-methylguanine-DNA
      methyltransferase (MGMT) causes gene silencing. This epigenetic modification has
      been associated with a favorable prognosis in adult patients with glioblastoma
      (GBM) who receive temozolomide and other alkylating agents. We explored MGMT
      promoter methylation in pediatric GBM and its relationship to survival and
      temozolomide sensitivity. PROCEDURE: We performed a retrospective study of MGMT
      promoter methylation in 10 pediatric GBM. The methylation status of the MGMT was
      determined using a 2-stage methylation specific PCR analysis on DNA extracted
      from tumor specimens which had been snap frozen at surgery. The relationships
      between MGMT promoter methylation and patient outcome and response to
      temozolomide were evaluated. RESULTS: Four of our 10 pediatric patients with GBM
      were found to have methylation of the MGMT gene promoter. Methylation of the MGMT
      promoter was shown to correlate (P = 0.0005) with survival. The average survival
      time for patients with methyltated MGMT was 13.7 months as compared to 2.5 months
      for the 6 patients with unmethylated MGMT promoter. Of the seven patients that
      received temozolomide, those patients that had the methylated MGMT gene promoter
      responded better to treatment (P = 0.007). CONCLUSIONS: As in adults, pediatric
      GBM patients with methylated MGMT promoter benefited from temozolomide. However,
      a stronger correlation with overall survival, regardless of treatment, was
      observed in this group of patients. These data suggest that MGMT methylation may
      be a prognostic factor for survival in pediatric GBM, as well as a marker for
      temozolomide sensitivity.

PMID- 16609954
TI  - Hepatocyte morphology and kinetics after portal vein embolization.
AB  - BACKGROUND: Macroscopic volume changes after portal vein embolization (PVE) can
      be assessed accurately by computed tomography, but histological changes remain
      poorly understood. The aim of this study was to clarify hepatocyte morphology and
      kinetics after PVE. METHODS: The resected livers from 25 patients who underwent
      extended hepatectomy after PVE and five normal livers were examined using
      hepatocyte paraffin 1 staining for histomorphometric analysis of hepatocytes.
      Cell kinetics were determined by Ki-67 staining and terminal deoxyribonucleotidyl
      transferase-mediated dUTP-digoxigenin nick-end labelling assay. Kupffer cells
      were examined by CD68 immunostaining. RESULTS: The number of hepatocytes was
      similar in the embolized lobe, non-embolized lobe and normal liver, but
      hepatocyte volume was greater in the non-embolized lobe than in the embolized
      lobe (P = 0.017). The Ki-67 labelling index was higher in the non-embolized lobe
      (P < 0.001) whereas the apoptotic index was higher in the embolized lobe (P <
      0.001). There were more Kupffer cells per unit area in the embolized lobe (P <
      0.001). CONCLUSION: Hepatocyte hypertrophy and replication leads to volume
      enlargement of the non-embolized hepatic lobe, whereas hepatocyte atrophy and
      apoptosis causes a decrease in volume of the embolized lobe.

PMID- 16609955
TI  - Malignant potential of solid pseudopapillary neoplasm of the pancreas.
AB  - BACKGROUND: Solid pseudopapillary neoplasms of the pancreas are rare malignant
      lesions of the pancreas that typically occur in young women. Large series from
      any one centre are notably absent in the literature. The aim of this study was to
      determine long-term outcomes of operative therapy. METHODS: The records of all 14
      patients diagnosed with pseudopapillary neoplasms of the pancreas over 17 years
      were reviewed. RESULTS: Thirteen of the 14 patients were female and the mean age
      at diagnosis was 30 years. Solid pseudopapillary neoplasm was suspected in only
      half of these patients before operation. On computed tomography, ultrasonography
      and/or magnetic resonance imaging, three lesions were solid, three were largely
      cystic, and five had solid and cystic components. All 14 patients underwent
      surgical exploration and curative resections were possible in 13, including
      distal pancreatectomy in nine, pancreaticoduodenectomy in three and resection of
      a local intraperitoneal recurrence in one patient. After follow-up ranging from 3
      months to 20 years, 12 patients were alive, including one who had undergone re
      exploration and resection of local and subcutaneous recurrences 9 years
      previously. CONCLUSION: Solid pseudopapillary neoplasm of the pancreas should be
      considered in the differential diagnosis of any solid or partly cystic pancreatic
      mass in women aged less than 35 years. An attempt at en bloc resection without
      formal lymphadenectomy should be undertaken, including resection of synchronous
      or metachronous distant metastases.

PMID- 16609956
TI  - Safety and efficacy of endoscopic retroperitoneal adrenalectomy.
AB  - BACKGROUND: Minimally invasive adrenalectomy has replaced open surgery in the
      treatment of benign adrenal tumours. Transperitoneal and retroperitoneal
      approaches have been advocated. However, long-term outcome data are rare.
      METHODS: Over a period of 8 years, 123 patients underwent surgery for benign
      adrenal lesions using the endoscopic retroperitoneal approach. Data were analysed
      retrospectively by review of medical charts. Long-term results were obtained by
      sending questionnaires to patients and contacting their primary physicians.
      RESULTS: One hundred and twenty-three patients underwent 126 endoscopic
      retroperitoneal adrenalectomies. Mean operating time for unilateral adrenalectomy
      was 115 min, whereas that for bilateral adrenalectomy was 208 min. The conversion
      rate was 4.8 per cent. Complications occurred after 15.9 per cent of
      adrenalectomies. One patient died during the postoperative period. Long-term
      results were obtained in 80 patients (74.8 per cent). Nine patients (11 per cent)
      reported chronic incisional pain and six patients (8 per cent) had chronic
      abdominal pain. Addisonian crisis after bilateral adrenalectomy occurred in three
      patients. Most patients (86 per cent) were satisfied with the cosmetic results.
      CONCLUSION: Endoscopic retroperitoneal adrenalectomy is a safe and effective
      procedure. Long-term outcome is acceptable and the procedure has excellent
      cosmetic results.

PMID- 16609957
TI  - Comparison of cell lines for stable production of fucose-negative antibodies with
      enhanced ADCC.
AB  - Several methods have been described to enhance antibody-dependent cellular
      cytotoxicity (ADCC) using different host cells that produce antibody with reduced
      levels of fucose on their carbohydrates. We compared the suitability of these
      methods for the serum-free fed-batch production of antibody for clinical trials
      and commercial uses. Recombinant anti-human CD20 chimeric IgG1-producing clones
      were established from host-cells that have been shown to produce more than 90%
      fucose-negative antibody. The cell lines were a FUT8 (alpha-1,6
      fucosyltransferase) knockout Chinese hamster ovary (CHO) cell line, Ms704, and
      two Lens culinaris agglutinin (LCA)-resistant cell lines, one derived from a
      variant CHO line, Lec13 and the other from a rat hybridoma cell line, YB2/0. The
      amount of fucose-negative antibody produced by Lec13 and YB2/0 significantly
      decreased with the culture. The increase in fucosylation was due to remaining
      synthesis of GDP-fucose via de novo pathway for the CHO line and the elevation of
      FUT8 expression by the YB2/0 cells. In contrast, Ms704 cells stably produced
      fucose-negative antibody with a consistent carbohydrate structure until the end
      of the culture. The productivity of the Ms704 cells reached 1.76 g/L with a
      specific production rate (SPR) of 29 pg/cell/day for 17 days in serum-free fed
      batch culture using a 1 L spinner bioreactor. Our results demonstrate that FUT8
      knockout has the essential characteristics of host cells for robust manufacture
      of fucose-negative therapeutic antibodies with enhanced ADCC.

PMID- 16609958
TI  - Kinetics of endothelin-induced inhibition and glucose permeability of astrocyte
      gap junctions.
AB  - Gap junctions contribute to important functions of communicating glial cells in
      brain physiology and pathology. Endothelins (ETs), a vasoactive family of
      peptides present in the brain, have been described as potent inhibitors of
      astrocyte gap junctional communication. Through dye-coupling studies we
      demonstrate here that this inhibition occurs rapidly and then successively
      reverses and returns to control levels after 90 min of continuous ET1 or ET3
      exposure. In addition, long-term exposure of cells to ET3, which acts mainly on
      ETB receptors, also desensitized the acute action of ET1, which was previously
      shown to act through either ETA or ETB receptor sites, or both. The gap junction
      blocker carbenoxolone did not show any time-dependent desensitization and was
      fully effective also in cultures treated with ETs for prolonged times. The ETs
      inhibitory effects were partially prevented when blocking pertussis toxin
      sensitive G-proteins, chelating intracellular Ca2+, or omitting extracellular
      Ca2+. We further show that ETs modulate gap junction-mediated transfer of 2-[N-(7
      nitrobenz-2-oxa-1,3-diazol-4-Y1)amino]-2-deoxyglucose (2-NBDG), a fluorescent
      glucose molecule, indicating a role of astrocyte gap junction coupling in
      metabolic trafficking and suggesting the importance of these peptides in the
      control of intercellular diffusion of energetic compounds. These findings might
      have particular relevance in early tissue reactions after various cerebral
      injuries, which commonly involve increased cerebral ET levels.

PMID- 16609959
TI  - Cannabinoid agonist WIN55,212-2 induces apoptosis in cerebellar granule cells via
      activation of the CB1 receptor and downregulation of bcl-xL gene expression.
AB  - The endogenous cannabinoid system is involved in the regulation of a number of
      physiologic effects in both the central and peripheral nervous systems. Its role
      in the control of neuronal cell proliferation has attracted major attention
      because of its potential implications for new therapeutic strategies. In the
      present study, we demonstrated that treatment of cultured cerebellar granule
      cells with the synthetic cannabinoid WIN55,212-2, causes cell-body and nuclear
      shrinkage, which are hallmarks of neuronal apoptosis, as well as concentration
      dependent decrease in cell viability. Staining with the fluorescent nuclear dye,
      Hoechst 33258, revealed apoptosis in 27.1% and 58.5% of cells exposed to 1 and 10
      microM of WIN55,212-2, respectively (P < 0.01 and P < 0.001 vs. control
      respectively) after 36 hr. After 24 hr of exposure to WIN55,212-2, mRNA levels
      for the anti-apoptotic gene bcl-xL were reduced to 45.6% of those found in
      control (P < 0.01). These effects were completely reverted when cells were
      exposed to the synthetic cannabinoid in the presence of the specific CB1-receptor
      antagonist, SR141716A (1 microM). Moreover, the pro-apoptotic effect of 10 microM
      WIN55,212-2 could be reduced by the addition to the incubation medium of a cell
      permeant inhibitor of caspase-1 (50 nM). Finally, WIN55,212-2 significantly
      increased caspase-1 activity after 24 hr. These findings show that the activation
      of CB1 receptors on cerebellar granule cells induces apoptotic cell death, which
      is associated with downregulation of the anti-apoptotic gene, bcl-xL, and at
      least in part, activation of caspase-1.

PMID- 16609960
TI  - Assembly of a perivascular astrocyte protein scaffold at the mammalian blood
      brain barrier is dependent on alpha-syntrophin.
AB  - alpha-Syntrophin, a member of the dystrophin-associated protein complex, is
      required for proper localization of the water channel aquaporin-4 at the blood
      brain barrier. Mice lacking alpha-syntrophin have reduced levels of aquaporin-4
      in perivascular astroglial endfeet. Consequently, they exhibit reduced edema and
      infarct volume in brain trauma models and reduced K+ clearance from the neuropil,
      leading to increased seizure susceptibility. We have used the alpha-syntrophin
      null mice to investigate whether alpha-syntrophin is required for proper
      localization of other components of the dystrophin complex at the blood-brain
      barrier. We find that alpha-syntrophin is required for the full recruitment of
      gamma2-syntrophin and alpha-dystrobrevin-2 to glial endfeet in adult cerebellum.
      In contrast, the localization of beta1- and beta2-syntrophin and alpha
      dystrobrevin-1 at the blood-brain barrier is not dependent on the presence of
      alpha-syntrophin. The localization patterns of alpha-dystrobrevin-1 and -2 in
      wild type cerebellum are strikingly different; while alpha-dystrobrevin-1 is
      present in glial endfeet throughout the cerebellum, alpha-dystrobrevin-2 is
      restricted to glial endfeet in the granular layer alone. Finally, we show that
      the enrichment of dystrophin in glial endfeet depends on the presence of alpha
      syntrophin. This finding is the first demonstration that dystrophin localization
      is dependent on syntrophin. Since the localization of gamma2-syntrophin, alpha
      dystrobrevin-2, and dystrophin is contingent on alpha-syntrophin, we conclude
      that alpha-syntrophin is a central organizer of the astrocyte dystrophin complex,
      an important molecular scaffold for localization of aquaporin-4 at the blood
      brain barrier.

PMID- 16609961
TI  - Proteasome inhibition by MG-132 induces apoptotic cell death and mitochondrial
      dysfunction in cultured rat brain oligodendrocytes but not in astrocytes.
AB  - Proteasomal dysfunction has been implicated in neurodegenerative disorders and
      during aging processes. In frontotemporal dementias, corticobasal degeneration,
      and progressive supranuclear palsy, oligodendrocytes are specifically damaged.
      Application of proteasomal inhibitors to cultured oligodendrocytes is associated
      with apoptotic cell death. The present study was undertaken to investigate the
      death pathway activated in oligodendrocytes by proteasomal inhibition. Our data
      show that the proteasomal inhibitor MG-132 causes oxidative stress, as indicated
      by the upregulation of the small heat shock protein heme oxygenase-1 (HO-1) and
      the appearance of oxidized proteins. Activation of the mitochondrial pathway was
      involved in the apoptotic process. Mitochondrial membrane potential was
      disturbed, and cytochrome c was released from the mitochondria. Concomitantly,
      death-related caspases 3 and 9 were activated and poly(ADP-ribose)-polymerase
      cleavage occurred. MG-132-induced cell death, DNA-fragmentation, and caspase
      activation could be prevented by the broad caspase inhibitor zVAD-fmk. In
      contrast to oligodendrocytes, cultured astrocytes showed resistance to the
      treatment with proteasomal inhibitors and did not reveal cytotoxic responses.
      This was also observed in astrocytes differentiated in the presence of dibutyryl
      cyclic AMP. Hence, individual cells respond differently to proteasomal inhibition
      and the therapeutic use of proteasomal inhibitors, e.g. for the treatment of
      cancer or inflammatory diseases, needs to be carefully evaluated.

PMID- 16609962
TI  - Accumulation of LPS by polyethylene particles decreases bone attachment to
      implants.
AB  - Molecules absorbed on the surface of particulate wear debris may contribute to
      inflammatory reactions that lead to aseptic loosening of implants.
      Lipopolysaccharide (LPS), a bacterial endotoxin, can attach to many biomaterials
      and stimulate macrophages to secrete osteoclast-activating cytokines. We tested
      the adsorption of LPS by polyethylene particles in vitro and examined the
      biological effects of LPS absorption on bone remodeling around implants in vivo.
      Polyethylene particles were incubated in radiolabeled LPS solutions, and
      adsorption of LPS by the particles was quantified by radioassay. Because
      polyethylene particles are hydrophobic and less dense than water, they floated
      and clumped when incubated in a water solution of LPS, resulting in low
      adsorption of LPS. However, when particles were incubated in an ethanol solution
      of LPS, most of the LPS was adsorbed by the particles, and was resistant to
      washing with water. Triton X-100 (10%), however, effectively washed the LPS off
      the particles. In a rat model, the presence of polyethylene particles around the
      implant in the femoral canal decreased bone attachment to the implant at 6 weeks.
      Incubating the particles with LPS before implantation, or intermittent
      administration of LPS systemically, further decreased bone-implant attachment to
      similar extents, but had no effect on the bone density of the control side
      femurs. Our data indicate that polyethylene particles have high affinity for LPS,
      depending on many factors, especially the solvents of the LPS. Intermittent
      systemic administration of LPS affects bone remodeling but only occurs in the
      area containing polyethylene particles and titanium implants, supporting the
      hypothesis that the presence of polyethylene particles around implants can result
      in accumulation of LPS from exogenous sources. This may cause local levels of LPS
      that are high enough to affect bone remodeling around implants.

PMID- 16609963
TI  - Six DOF in vivo kinematics of the ankle joint complex: Application of a combined
      dual-orthogonal fluoroscopic and magnetic resonance imaging technique.
AB  - Accurate knowledge of in vivo ankle joint complex (AJC) biomechanics is critical
      for understanding AJC disease states and for improvement of surgical treatments.
      This study investigated 6 degrees-of-freedom (DOF) in vivo kinematics of the
      human AJC using a combined dual-orthogonal fluoroscopic and magnetic resonance
      imaging (MRI) technique. Five healthy ankles of living subjects were studied
      during three in vivo activities of the foot, including maximum plantarflexion and
      dorsiflexion, maximum supination and pronation, and three weight-bearing
      positions in simulated stance phases of walking. A three-dimensional (3D)
      computer model of the AJC (including tibia, fibula, talus, and calcaneus) was
      constructed using 3D MR images of the foot. The in vivo AJC position at each
      selected position of the foot was captured using two orthogonally positioned
      fluoroscopes. In vivo AJC motion could then be reproduced by coupling the
      orthogonal images with the 3D AJC model in a virtual dual-orthogonal fluoroscopic
      system. From maximum dorsiflexion to plantarflexion, the arc of motion of the
      talocrural joint (47.5 +/- 2.2 degrees) was significantly larger than that of the
      subtalar joint (3.1 +/- 6.8 degrees). Both joints showed similar degrees of
      internal-external and inversion-eversion rotation. From maximum supination to
      pronation, all rotations and translations of the subtalar joint were
      significantly larger than those of the talocrural joint. From heel strike to
      midstance, the plantarflexion contribution from the talocrural joint (9.1 +/- 5.3
      degrees) was significantly larger than that of the subtalar joint (-0.9 +/- 1.2
      degrees). From midstance to toe off, internal rotation and inversion of the
      subtalar joint (12.3 +/- 8.3 degrees and -10.7 +/- 3.8 degrees, respectively)
      were significantly larger than those of the talocrural joint (-1.6 +/- 5.9
      degrees and -1.7 +/- 2.7 degrees). Strong kinematic coupling between the
      talocrural and subtalar joints was observed during in vivo AJC activities. The
      contribution of the talocrural joint to active dorsi-plantarflexion was higher
      than that of the subtalar joint, whereas the contribution of the subtalar joint
      to active supination-pronation was higher than that of the talocrural joint. In
      addition, the talocrural joint demonstrated larger motion during the early part
      of stance phase while the subtalar joint contributes more motion during the later
      part of stance phase. The results add quantitative data to an in vivo database of
      normals that can be used in clinical diagnosis, treatment, and evaluation of the
      AJC after injuries.

PMID- 16609964
TI  - Effect of aging and degeneration on disc volume and shape: A quantitative study
      in asymptomatic volunteers.
AB  - Debate continues on the effect of disc degeneration and aging on disc volume and
      shape. So far, no quantitative in vivo MRI data is available on the factors
      influencing disc volume and shape. The objective of this MRI study was to
      quantitatively investigate changes in disc height, volume, and shape as a result
      of aging and/or degeneration omitting pathologic (i.e., painful) disc
      alterations. Seventy asymptomatic volunteers (20-78 years) were investigated with
      sagittal T1- and T2-weighted MR-images encompassing the whole lumbar spine. Disc
      height was determined by the Dabbs method and the Farfan index. Disc volume was
      calculated by the Cavalieri method. For the disc shape the "disc convexity index"
      was calculated by the ratio of central disc height and mean anterior/posterior
      disc height. Disc height, disc volume, and the disc convexity index measurements
      were corrected for disc level and the individuals age, weight, height, and sex in
      a multilevel regression analysis. Multilevel regression analysis showed that disc
      volume was negatively influenced by disc degeneration (p < 0.001) and positively
      correlated with body height (p < 0.001) and age (p < 0.01). Mean disc height and
      the disc convexity index were negatively influenced by disc degeneration but not
      by gender, weight, and height. Disc height was positively correlated with age (p
      < 0.01). From the results of this study, it can be concluded that disc
      degeneration generally results in a decrease of disc height and volume as well as
      a less convex disc shape. In the absence of disc degeneration, however, age tends
      to result in an inverse relationship on disc height, volume, and shape.

PMID- 16609965
TI  - Expression of the angiomatrix and angiogenic proteins CYR61, CTGF, and VEGF in
      osteonecrosis of the femoral head.
AB  - Angiogenesis and bone repair are closely linked processes. VEGF, CYR61, and CTGF
      have been identified as signaling factors that control angiogenesis and could be
      important in fracture healing. The purpose of this study was to investigate the
      expression of these signaling factors in osteonecrosis of the femoral head.
      Twenty-one bone cylinders were retrieved from hips of patients with osteonecrosis
      of the femoral head at different ARCO stages. Immunohistochemistry for CD34,
      CYR61, CTGF, and VEGF expression was done on each bone cylinder representing the
      different regions of osteonecrosis (necrosis, fibrosis, transition zone, and
      edematous area). VEGF, CYR61, and CTGF were expressed in samples with
      osteonecrosis. Particularly VEGF and CYR61 were highly expressed in the edematous
      area. CYR61 was also highly expressed in the transition zone. CTGF was expressed
      mainly in the area of marrow fibrosis and edema. CYR61, CTGF, and VEGF are
      expressed to different degrees in the different repair zones of osteonecrosis.
      Particularly, the high expression of VEGF and CYR61 in the edematous area may
      represent a consequence of hypoxia and indicate a role of these proteins in the
      repair processes ongoing in osteonecrosis.

PMID- 16609966
TI  - Density and structural changes in the bone of growing rats after weekly
      alendronate administration with and without a methotrexate challenge.
AB  - Alendronate (ALN) and other bisphosphonates have been used successfully in
      pediatric patients with osteopenia secondary to connective tissue diseases. Loss
      of growth in height has not been reported, but concerns remain regarding the
      effect of these potent antiresorptive agents when used in children and
      adolescents. High-dose methotrexate (MTX) and other chemotherapy drugs have been
      implicated in osteoporosis and a high fracture incidence in survivors of
      childhood cancers and are also associated with osteopenia in adult animals. The
      effect of high dose MTX on bone density during rapid skeletal growth, however,
      has not been widely studied, nor has the potentially therapeutic effect of
      bisphosphonates in this setting. We examined the effects of ALN and MTX
      administration, alone and in combination, on bone density, morphology, mechanical
      strength, and longitudinal growth in normal growing rats. Sprague-Dawley rats
      were given ALN once weekly (0.3 mg/kg) from 5 to 11 weeks of age, with and
      without a course of methotrexate (MTX) given daily in weeks 1 and 3 (0.75
      mg/kg/day). Twenty-four animals were randomly divided into four groups: Control
      (vehicle), ALN alone, ALN + MTX, and MTX alone. After 6 weeks, the femora,
      tibiae, and lumbar spine were studied by dual-energy X-ray absorptiometry,
      peripheral quantitative computed tomography, mechanical strength testing,
      microradiography, light microscopy, and by determination of ash weights and bone
      lengths. ALN treatment increased bone mineral density (BMD) by 23% to 68%. The
      largest increases in the femur occurred in the distal third where endochondral
      bone growth was greatest and included large increases in trabecular bone and
      total cross-sectional area. ALN + MTX produced similar effects to ALN alone. MTX
      only reduced BMD by 8% in the vertebrae, but not significantly at other sites.
      MTX also led to femoral length reductions of 2.9%. The small reductions in BMD
      due to MTX were overwhelmed by the increases due to ALN, whereas the length loss
      was unaffected. Transverse density banding corresponding to weekly ALN
      administrations were clearly evident radiographically throughout the growing
      skeleton, likely due to decreased resorption and possibly increased
      mineralization in the bands. ALN or ALN + MTX treatment also led to increases in
      mechanical strength in the femora. Although MTX administration during growth
      leads to some BMD reduction, ALN given with MTX eliminates this reduction and in
      fact bone density and strength increase above control levels.

PMID- 16609967
TI  - Regional gene therapy for full-thickness articular cartilage lesions using naked
      DNA with a collagen matrix.
AB  - A novel gene therapy approach for treating damaged cartilage is proposed that
      involves placing endotoxin-free cDNA containing the gene for bone morphogenetic
      protein-2 (BMP-2) in type I collagen sponges and then transferring the naked
      plasmid DNA construct to the injury site. A full-thickness cartilaginous defect
      in rabbits implanted with plasmid containing a marker gene (beta-galactosidase)
      showed expressed protein as detected by immunostaining. At 1 week
      postimplantation, mesenchymal cells subjacent to the defect had incorporated the
      implanted naked plasmid DNA and, once transfected, served as local bioreactors,
      transiently producing the gene product. Plasmids containing the gene for BMP-2
      implanted in collagen sponges in cartilage lesions stimulated hyalinelike
      articular cartilage repair at 12 weeks postimplantation, nearly equivalent in
      quality to that induced by collagen sponges with recombinant BMP-2 protein. Our
      approach circumvents the risks of inflammation and immunogenic response
      associated with the use of viral vectors. Naked plasmid DNA as a vehicle for
      transferring therapeutic genes has been shown to be effective in a therapeutic
      model within rabbit articular cartilage and appears to be safe and cost
      effective.

PMID- 16609968
TI  - Histological and scanning electron microscopy analyses of bone/implant interface
      using the novel Bonelike synthetic bone graft.
AB  - Synthetic bone grafts provide an alternative to autografts and allografts.
      Bonelike is a patented synthetic bone graft that mimics the mineral composition
      of bone. The aim of the present work was to assess the biological behavior of
      Bonelike graft in humans, before using the material in orthopedic applications of
      bone regeneration, for example, in opening wedge high tibial osteotomies for
      medial knee osteoarthritis. Bonelike granules were implanted in cortical bone of
      11 patients undergoing osteotomies, and new bone formation, osteoconductive
      properties, and resorption characteristics of the granules were analyzed. The
      granules ranged from 500 to 1000 microm and were implanted in the lateral aspect
      of the tibia. The patients' mean age was 59 years (range 48 to 70 years); there
      were eight women and three men, all suffering from medial compartment
      osteoarthritis of the knee. At surgery, a 1 x 1 x 1-cm cortical defect was
      created 3 cm distal to the entry point of the screws, in line with the long axis
      of tibia. The implanted Bonelike graft sample was extracted for analysis during
      removal of the metallic prosthesis after implantation times of 6, 9, and 12
      months. Radiological follow-up, scanning electron microscopy, histological
      analysis, and histomorphometric measurements were conducted on the retrieved
      samples to assess bone regeneration in the defect area. Osteoconductive capacity
      was demonstrated by extensive mature bone formation around the implanted granules
      and high levels of percentage bone-to-graft contact (from 67-84%). Bonelike acted
      as an excellent bioactive scaffold, allowing the migration, proliferation, and
      differentiation of bone cells on its surface, and therefore regeneration of the
      defects was achieved in a rapid, controlled manner. Our results suggest that
      Bonelike graft is an excellent candidate for orthopedic applications where rapid
      new bone formation is a fundamental requirement.

PMID- 16609969
TI  - Oral gene delivery: design of polymeric carrier systems shielding toward
      intestinal enzymatic attack.
AB  - The gastrointestinal tract poses a variety of morphological and physiological
      barriers to the expression of target genes. The aim of this study was to evaluate
      the stability of cationic polymer/pDNA nanoparticles toward salts and enzymes of
      the intestinal fluid. Within this study, a chitosan-enzyme inhibitor conjugate
      has been generated and characterized. Based on this conjugate, nanoparticles with
      pDNA were generated to enhance transfection rate in oral gene delivery. The
      enzyme inhibitor aurintricarboxylic acid (ATA) was covalently bound to chitosan
      to improve the enzymatic stability of nanoparticles formed with this polymer and
      pDNA. Chitosan-ATA/pDNA nanoparticles showed a size of 98.5 +/- 26 nm and a zeta
      potential of -13.26 +/- 0.24 mV (n = 3-4). Stability studies with salt solution,
      lysozyme, DNase, and freshly collected porcine intestinal fluid showed that
      chitosan-ATA/pDNA nanoparticles are significantly (p < 0.05) more stable than
      unmodified chitosan/pDNA nanoparticles. Apart from improved stability, chitosan
      ATA/pDNA nanoparticles showed a 2.6-fold higher transfection rate than
      chitosan/pDNA nanoparticles in the Caco-2 cell line, thus creating a promising
      carrier for orally administered therapeutic genes.

PMID- 16609970
TI  - Fibrous long spacing type collagen fibrils have a hierarchical internal
      structure.
AB  - Nanodissection of single fibrous long spacing (FLS) type collagen fibrils by
      atomic force microscopy (AFM) reveals hierarchical internal structure: Fibrillar
      subcomponents with diameters of approximately 10 to 20 nm were observed to be
      running parallel to the long axis of the fibril in which they are found. The
      fibrillar subcomponent displayed protrusions with characteristic approximately
      270 nm periodicity, such that protrusions on neighboring subfibrils were aligned
      in register. Hence, the banding pattern of mature FLS-type collagen fibrils
      arises from the in-register alignment of these fibrillar subcomponents. This
      hierarchical organization observed in FLS-type collagen fibrils is different from
      that previously reported for native-type collagen fibrils, displaying no
      supercoiling at the level of organization observed.

PMID- 16609971
TI  - Diffusion-collision of foldons elucidates the kinetic effects of point mutations
      and suggests control strategies of the folding process of helical proteins.
AB  - In this article we use mutation studies as a benchmark for a minimal model of the
      folding process of helical proteins. The model ascribes a pivotal role to the
      collisional dynamics of a few crucial residues (foldons) and predicts the folding
      rates by exploiting information drawn from the protein sequence. We show that our
      model rationalizes the effects of point mutations on the kinetics of folding. The
      folding times of two proteins and their mutants are predicted. Stability and
      location of foldons have a critical role as the determinants of protein folding.
      This allows us to elucidate two main mechanisms for the kinetic effects of
      mutations. First, it turns out that the mutations eliciting the most notable
      effects alter protein stability through stabilization or destabilization of the
      foldons. Secondly, the folding rate is affected via a modification of the foldon
      topology by those mutations that lead to the birth or death of foldons. The few
      mispredicted folding rates of some mutants hint at the limits of the current
      version of the folding model proposed in the present article. The performance of
      our folding model declines in case the mutated residues are subject to strong
      long-range forces. That foldons are the critical targets of mutation studies has
      notable implications for design strategies and is of particular interest to
      address the issue of the kinetic regulation of single proteins in the general
      context of the overall dynamics of the interactome.

PMID- 16609972
TI  - Global multiple-sequence alignment with repeats.
AB  - Repeating fragments in biological sequences are often essential for structure and
      function. Over the years, many methods have been developed to recognize repeats
      or to multiply align protein sequences. However, the integration of these two
      methodologies has been largely unexplored to date. Here, we present a new method
      capable of globally aligning multiple input sequences under the constraints of a
      given repeat analysis. The method supports different stringency modes to adapt to
      various levels of detail and reliability of the repeat information available.

PMID- 16609973
TI  - Safety of, and biological and functional response to, a novel metallic implant
      for the management of focal full-thickness cartilage defects: Preliminary
      assessment in an animal model out to 1 year.
AB  - Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC)
      can cause pain and functional impairment. Affected middle-aged patients respond
      unpredictably to existing treatments and knee arthroplasty may be required,
      prompting risk of revision. This study assesses the safety of, and biological and
      functional response to, a metallic resurfacing implant which may delay or obviate
      the need for traditional arthroplasty. The anatomic contour of the surgically
      exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full
      thickness osteochondral defect was created. An anchor-based Co-Cr resurfacing
      implant, matching the mapped articular contour, was implanted. Each goat's
      contralateral unoperated femorotibial joint was used as a control. Postoperative
      outcome was assessed by lameness examination, radiography, arthroscopy,
      synoviocentesis, necropsy, and histology up to 26 (n = 3) or 52 (n = 3) weeks. By
      postoperative week (POW) 4, goats demonstrated normal range of motion, no joint
      effusion, and only mild lameness in the operated limb. By POW 26 the animals were
      sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed
      moderate synovial inflammation and a chondral membrane extending centrally across
      the implant surface. Radiographs at POWs 14 to 52 implied implant stability in
      the operated joints, as well as subchondral bone remodeling and mild exostosis
      formation in the operated and contralateral unoperated joints of some goats. By
      POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26
      and 52 MFC cartilage was metachromatic and intact in the operated and unoperated
      femorotibial joints. Proximal tibiae of some operated and unoperated limbs
      demonstrated limited subchondral bone remodeling and foci of articular cartilage
      fibrillation and thinning. The chondral membrane crossing the prosthesis
      possessed a metachromatic matrix containing singular and clustered chondrocytes.
      Our data imply the safety, biocompatibility, and functionality of the implant.
      Focal articular damage was documented in the operated joints at POWs 26 and 52,
      but lesions were much reduced over those previously reported in untreated
      defects. Expanded animal or preclinical human studies are justified.

PMID- 16609974
TI  - Multifocal acquired demyelinating sensory and motor neuropathy presenting as a
      peripheral nerve tumor.
AB  - A man with multifocal acquired demyelinating sensory and motor neuropathy
      (MADSAM), or Lewis-Sumner syndrome, presented with a progressive left lumbosacral
      plexus lesion resembling a neurofibroma. After 7 years he developed a left ulnar
      nerve lesion with conduction block in its upper segment. Treatment with
      intravenous immunoglobulin improved the symptoms and signs of both lesions. We
      conclude that inflammatory neuropathy must be considered in the differential
      diagnosis of peripheral nerve tumors, and that unifocal lesions may precede
      multifocal involvement in MADSAM by several years. In addition, we discuss the
      clinical features in 9 patients attending a specialist peripheral nerve clinic
      and review the literature.

PMID- 16609975
TI  - A case of Lewis-Sumner syndrome with conduction abnormalities only in the
      brachial plexus and roots.
AB  - We present a case of subacute weakness of one hand with unusual sensory
      involvement including the upper thorax. Despite normal distal conduction studies,
      a clinical diagnosis of Lewis-Sumner syndrome was made and the patient responded
      well to intravenous immunoglobulins. Repeated studies after clinical exacerbation
      finally proved the demyelinating nature of the neuropathy using proximal magnetic
      nerve stimulation. This case underlies the importance of seeking proximal
      conduction blocks in patients with suspected demyelinating neuropathy.

PMID- 16609976
TI  - In vivo study on the healing of bone defects treated with bone marrow stromal
      cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in
      combination.
AB  - The repair of confined trabecular bone defects in rabbits treated by autologous
      bone marrow stromal cells (BMSC), platelet-rich plasma (PRP), freeze-dried bone
      allografts (FDBA) alone and in combination (BMSC + PRP; FDBA + BMSC; FDBA + PRP;
      FDBA + PRP + BMSC) was compared. A critical size defect was created in the distal
      part of the femurs of 48 adult rabbits. Histology and histomorphometry were used
      in the evaluation of healing at 2, 4, and 12 weeks after surgery. The healing
      rate (%) was calculated by measuring the residual bone defect area. Architecture
      of the newly formed bone was compared with that of bone at the same distal femur
      area of healthy rabbits. The defect healing rate was higher in PRP + BMSC, FDBA +
      PRP, FDBA + BMSC, and FDBA + PRP + BMSC treatments, while lower values were
      achieved with PRP treatment at all experimental times. The highest bone-healing
      rate at 2 weeks was achieved with FDBA + PRP + BMSC treatment, which resulted
      significantly different from PRP (p < 0.05) and BMSC (p < 0.05) treatments. At 4
      weeks, the bone-healing rate increased except for PRP treatment. Finally, the
      bone-healing rate of FDBA + PRP, FDBA + BMSC, and FDBA + PRP + BMSC was
      significantly higher than that of PRP at 12 weeks (p < 0.05). At 12 weeks,
      significant differences still existed between PRP, BMSC, and FDBA groups and
      normal bone (p < 0.05). These results showed that the combination of FDBA, BMSC
      and PRP permitted an acceleration in bone healing and bone remodeling processes.

PMID- 16609977
TI  - Interrater reliability of the needle examination in lumbosacral radiculopathy.
AB  - Low back pain and lumbar radiculopathy are among the most common painful
      disorders affecting the adult population. This study hypothesizes that there is
      good correlation between the diagnostic impression of an unblinded
      electromyographer, using clinical and electromyographic information, and an
      independent electromyographer, who uses the needle examination only to assess for
      lumbar radiculopathy. This is a prospective, single-blinded, observational pilot
      study. The needle examination was electronically recorded, reproduced, and shown
      to a second examiner, blinded to all clinical data. Diagnostic impressions from
      both examiners were recorded and evaluated for agreement. Six recorded cases were
      reviewed by 66 blinded examiners. Overall diagnostic agreement was 46.9% (60.5%
      faculty level, 28.5% resident level). Logistic regression shows a strong
      association between training level and agreement on diagnostic impression (odds
      ratio, 1.9; 95% confidence interval, 1.12-3.22; P = 0.019). This study shows that
      there is fair interrater reliability between faculty-level examiners and poor
      reliability among resident-level examiners when the needle examination is used to
      evaluate patients with lumbar radiculopathy.

PMID- 16609978
TI  - Inappropriate surgeries resulting from misdiagnosis of early amyotrophic lateral
      sclerosis.
AB  - Initial symptoms of amyotrophic lateral sclerosis (ALS) may mimic radiculopathy,
      myelopathy, mononeuropathy, or arthropathy. A retrospective review of 260
      consecutive patients with ALS evaluated between 1996 and 2004 revealed that 55
      (21%) had had surgery within the 5 years prior to ALS diagnosis. Thirty-four of
      these 55 (61%) had surgery for symptoms and signs that retrospectively were
      attributable to early manifestations of ALS. Misdiagnosis of early ALS may lead
      to unnecessary surgeries with their attendant potential complications.

PMID- 16609979
TI  - Effective therapy of transected quadriceps muscle in rat: Gastric
      pentadecapeptide BPC 157.
AB  - We report complete transection of major muscle and the systemic peptide treatment
      that induces healing of quadriceps muscle promptly and then maintains the healing
      with functional restoration. Initially, stable gastric pentadecapeptide BPC 157
      (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials
      for inflammatory bowel disease; wound treatment; no toxicity reported; effective
      alone without carrier) also superiorly accelerates the healing of transected
      Achilles tendon. Regularly, quadriceps muscle completely transected transversely
      1.0 cm proximal to patella presents a definitive defect that cannot be
      compensated in rat. BPC 157 (10 microg, 10 ng, 10 pg/kg) is given
      intraperitoneally, once daily; the first application 30 min posttransection, the
      final 24 h before sacrifice. It consistently improves muscle healing throughout
      the whole 72-day period. Improved are: (i) biomechanic (load of failure
      increased); (ii) function (walking recovery and extensor postural thrust/motor
      function index returned toward normal healthy values); (iii)
      microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments;
      absent gap; significant desmin positivity for ongoing regeneration of muscle;
      larger myofibril diameters on both sides, distal and proximal (normal healthy rat
      values reached)]; (iv) macroscopic presentation (stumps connected; subsequently,
      atrophy markedly attenuated; finally, presentation close to normal noninjured
      muscle, no postsurgery leg contracture). Thus, posttransection healing
      consistently improved-may suggest this peptide therapeutic application in muscle
      disorders.

PMID- 16609980
TI  - Interdomain mobility in di-ubiquitin revealed by NMR.
AB  - Domain orientation and dynamics can play an essential role in the function of
      multidomain proteins. Lys48-linked polyubiquitin chains, the principal signal for
      proteasomal protein degradation, adopt a closed conformation at physiological
      conditions, in which the functionally important residues Leu8, Ile44, and Val70
      are sequestered at the interdomain interface. This interface must open in order
      for these groups to become available for interactions with various chain
      recognition factors. Knowledge of the mechanism of domain motion leading to the
      opening of the interdomain interface in polyubiqutin is, therefore, essential for
      the understanding of the processes controlling molecular recognition events in
      polyubiquitin signaling. Here we use NMR to characterize the interdomain dynamics
      that open the interface in a di-ubiquitin chain. This process occurs via domain
      reorientations on a 10-ns time scale and with the amplitudes that are sufficient
      for making functionally important hydrophobic residues in polyubiquitin available
      for direct interactions with various ubiquitin-binding factors. The analysis
      revealed the structures of the interconverting conformational states of di
      ubiquitin and the rates and amplitudes of this process at near-physiological and
      acidic pH. The proposed mechanism of domain reorientation is quite general and
      could serve as a paradigm of interdomain mobility in other multidomain systems.

PMID- 16609981
TI  - A transient lesion in splenium of the corpus callosum in a patient with childhood
      onset anorexia nervosa.
AB  - OBJECTIVE: Although a transient lesion in the splenium of the corpus callosum
      (SCC) has been reported predominantly regarding patients with epilepsia, it is of
      rare occurrence, and its underlying biological basis remains unknown. This is a
      report of an SCC lesion in a patient with anorexia nervosa (AN). METHOD: The
      patient was a 15-year-old girl with childhood-onset (11 years) and a protracted
      course of AN. On admission, the patient showed no apparent neurological
      abnormalities. Magnetic resonance imaging (MRI) scans revealed a circumscribed
      lesion in the SCC. We treated her with nutritional rehabilitation supplemented
      with B vitamins. RESULTS: One month later, the lesion completely disappeared, but
      her weight was not restored. CONCLUSION: Treatment with B-vitamin supplementation
      may be beneficial for the treatment of patients with AN, in cases in which the
      disorder develops at an early age before brain maturation (i.e., childhood-onset
      cases), along with an enduring course of malnutrition.

PMID- 16609982
TI  - Familial and sociopsychopathological risk factors for suicide attempt in bulimic
      and in depressed women: prospective study.
AB  - OBJECTIVE: This study was carried out to examine sociopsychopathological
      predictors of prospective observed suicide attempts in bulimic women purging type
      without comorbid major depression (BNG) at the time of study entry and in woman
      with major depression without comorbid eating disorder at the time of study entry
      (MDG). METHODS: Data from 28 BNG (age 23.5 +/- 3.6) and 126 MDG women (age 33.4
      +/- 5.1) who had attempted suicide during 12 months' monitoring were compared.
      RESULTS: A univariate comparison of the two groups revealed various differences.
      Analysis of risk factors for suicide attempts using stepwise logistic regression
      was conducted separately for each group. The derived logistic models showed that
      patients from the BNG group had a history of higher incidence of sexual abuse in
      childhood, as well as abuse of laxatives and illicit drugs; they also lacked
      orientation in life, felt lonely despite family and friends, tended to direct
      their anger outward, and were unable to relax. CONCLUSIONS:
      Sociopsychopathological risk factors for suicide attempts in the BNG and MDG
      appear to vary.

PMID- 16609983
TI  - Familial aggregation in the night eating syndrome.
AB  - OBJECTIVE: This study examined the extent to which the night eating syndrome
      (NES) affects first-degree relatives of NES and control probands. METHOD: NES
      participants and controls were assessed with the Night Eating Questionnaire
      (NEQ), the Night Eating Syndrome History and Inventory (NESHI), 10 day sleep and
      food records, the Eating Disorder Examination (EDE), the Structured Clinical
      Interview for DSM IV Axis I Disorders (SCID I), and a Family History
      Questionnaire (FHQ) to assess the presence of NES among first-degree relatives. A
      proband predictive model, using logistic regression analyses and the generalized
      estimating equation to control for correlation among observations within families
      was used to assess familial aggregation. RESULTS: The odds of an NES proband
      having an affected first-degree relative were significantly greater than that of
      a control proband (odds ratio=4.9, p<.001). A number of covariates were included
      in the model: proband body mass index (BMI) (kg/m2), proband gender, proband age,
      proband ethnicity, first-degree relative gender, relationship to proband (i.e.,
      mother, father, or sibling), and the interaction between relationship to proband
      and proband status (night eater or control); none was statistically significant
      (p>.05). CONCLUSION: The study showed a strong aggregation of NES in families.

PMID- 16609984
TI  - Comorbidity between obesity and attention deficit/hyperactivity disorder:
      population study with 13-15-year-olds.
AB  - OBJECTIVE: This study analyzes whether obese children have a higher risk of
      attention deficit/hyperactivity "characteristics" (AD/HD) than do children with
      other nutritional states. METHOD: This study included 35,403 participants from
      486 community schools. They completed the AD/HD scale of the Strengths and
      Difficulties Questionnaire (SDQ) and were weighed and measured. 2879 of the
      participants were obese and 78 were morbidly obese (BMI>40). RESULTS: A discrete,
      nonsignificant, increment was found in the AD/HD characteristics of male
      participants with morbid obesity, as compared with the other nutritional states.
      Among morbidly obese females, the prevalence of AD/HD characteristics was
      slightly superior, although not significantly, to that found in participants with
      normal weight, overweight or obese (BMI<40). CONCLUSION: Among nonclinical
      populations with a communitarian origin, previous findings reporting high rates
      of AD/HD in obese children are not replicated. This increment in the prevalence
      of AD/HD among hospitalized obese children could be the result of selection bias.

PMID- 16609987
TI  - Gastrointestinal manifestations in myotonic muscular dystrophy.
AB  - Myotonic dystrophy (MD) is characterized by myotonic phenomena and progressive
      muscular weakness. Involvement of the gastrointestinal tract is frequent and may
      occur at any level. The clinical manifestations have previously been attributed
      to motility disorders caused by smooth muscle damage, but histologic evidence of
      alterations has been scarce and conflicting. A neural factor has also been
      hypothesized. In the upper digestive tract, dysphagia, heartburn, regurgitation
      and dyspepsia are the most common complaints, while in the lower tract, abdominal
      pain, bloating and changes in bowel habits are often reported. Digestive symptoms
      may be the first sign of dystrophic disease and may precede the musculo-skeletal
      features. The impairment of gastrointestinal function may be sometimes so gradual
      that the patients adapt to it with little awareness of symptoms. In such cases
      routine endoscopic and ultrasonographic evaluations are not sufficient and
      targeted techniques (electrogastrography, manometry, electromyography, functional
      ultrasonography, scintigraphy, etc.) are needed. There is a low correlation
      between the degree of skeletal muscle involvement and the presence and severity
      of gastrointestinal disturbances whereas a positive correlation with the duration
      of the skeletal muscle disease has been reported. The drugs recommended for
      treating the gastrointestinal complaints such as prokinetic, anti-dyspeptic drugs
      and laxatives, are mainly aimed at correcting the motility disorders.
      Gastrointestinal involvement in MD remains a complex and intriguing condition
      since many important problems are still unsolved. Further studies concentrating
      on genetic aspects, early diagnostic techniques and the development of new
      therapeutic strategies are needed to improve our management of the
      gastrointestinal manifestations of MD.

PMID- 16609989
TI  - Correlation of Epstein-Barr virus and its encoded proteins with Helicobacter
      pylori and expression of c-met and c-myc in gastric carcinoma.
AB  - AIM: To investigate the interrelationship of Epstein-Barr virus (EBV) and EBV-
      encoded proteins with Helicobacter pylori (H pylori) infection and the expression
      of c-met and c-myc oncogene proteins in gastric carcinoma, and to explore their
      role in gastric carcinogenesis. METHODS: One hundred and eighty-five gastric
      carcinoma tissues were detected by polymerase chain reaction (PCR)-Southern blot
      for EBV genome and in situ hybridization (ISH) for EBV-encoded small RNA 1
      (EBER1). Gastric carcinoma with positive EBER1 signals was confirmed EBV
      associated gastric carcinoma (EBVaGC). The status of H pylori infection in 185
      gastric carcinomas was assessed by rapid urease test and PCR. The samples with
      positive PCR and urease test were defined as H pylori infection. The expression
      of c-met and c-myc oncogene proteins in tissues of EBVaGC and matched EBV
      negative gastric carcinoma (EBVnGC) were examined by immunohistochemistry. RT-PCR
      and Southern hybridization were used to detect the expression of nuclear antigens
      (EBNAs) 1 and 2, latent membrane protein (LMP) 1, early genes BARF1 and BHRF1 in
      EBVaGC cases. RESULTS: The positive rate of H pylori and EBV in 185 gastric
      carcinomas was 59.45% (110/185) and 7.03% (13/185) respectively. No difference
      was found in sex, age, pathological differentiation, clinical stages and lymph
      node metastasis between H pylori-positive and H pylori-negative gastric
      carcinomas. However, the positive rate of H pylori infection in the antrum
      gastric carcinomas was higher than that of cardia and body gastric carcinomas. In
      our series, age, pathological differentiation, clinical stages, lymph node
      metastasis and location of cancer were not different between EBVnGC and EBVaGC,
      while the positive rate of EBV in male patients was significantly higher than
      that of female patients. The positivity of H pylori in EBV-associated and EBV
      negative gastric carcinomas was 46.15% (6/13) and 81.40%(104/172) respectively.
      There was no significant correlation between EBV and H pylori infection. The c
      met overexpression was significantly higher in the EBVaGC group than in the
      EBVnGC group. However, c-met and c-myc expression did not show significant
      difference between the two groups. Transcripts of EBNA1 were detected in all 13
      EBVaGCs, while both EBNA2 and LMP1 mRNA were not detected. Six of the 13 cases
      exhibited BARF1 transcripts and 2 exhibited BHRF1 transcripts. CONCLUSION: The
      positivity of H pylori in EBVnGCs is higher than that of EBVaGCs, but no
      significant correlation is found between EBV infection and H pylori infection. H
      pylori-positive gastric carcinoma is predominant in antrum location, while EBVaGC
      has a tendency of predominance in cardia/body location. EBV infection is
      associated with c-met abnormal expression but not with c-myc protein in EBVaGC. c
      met overexpression is not induced by LMP1. BARF1 and BHRF1 may play important
      roles in the tumorigenesis of EBVaGC through different pathways.

PMID- 16609988
TI  - Current concept on the pathogenesis of inflammatory bowel disease-crosstalk
      between genetic and microbial factors: pathogenic bacteria and altered bacterial
      sensing or changes in mucosal integrity take "toll" ?
AB  - The pathogenesis of inflammatory bowel disease (IBD) is only partially
      understood. Various environmental and host (e.g. genetic-, epithelial-, immune
      and non-immune) factors are involved. It is a multifactorial polygenic disease
      with probable genetic heterogeneity. Some genes are associated with IBD itself,
      while others increase the risk of ulcerative colitis (UC) or Crohn's disease (CD)
      or are associated with disease location and/or behaviour. This review addresses
      recent advances in the genetics of IBD. The article discusses the current
      information on the crosstalk between microbial and genetic factors (e.g.
      NOD2/CARD15, SLC22A46A5 and DLG5). The genetic data acquired in recent years help
      in understanding the pathogenesis of IBD and can identify a number of potential
      targets for therapeutic intervention. In the future, genetics may help more
      accurately diagnose and predict disease course in IBD.

PMID- 16609990
TI  - Anemia and long-term outcome in adjuvant and neoadjuvant radiochemotherapy of
      stage II and III rectal adenocarcinoma: the Freiburg experience (1989-2002).
AB  - AIM: To evaluate the long-term outcome of standard 5-FU based adjuvant or
      neoadjuvant radiochemotherapy and to identify the predictive factors, especially
      anemia before and after radiotherapy as well as hemoglobin increase or decrease
      during radiotherapy. METHODS: Two hundred and eighty-six patients with Union
      International Contre Cancer (UICC) stage II and III rectal adenocarcinomas, who
      underwent resection by conventional surgical techniques (low anterior or
      abdominoperineal resection), received either postoperative (n=233) or
      preoperative (n=53) radiochemotherapy from January 1989 until July 2002. Overall
      survival (OAS), cancer-specific survival (CSS), disease-free survival (DFS),
      local-relapse-free (LRS) and distant-relapse-free survival (DRS) were evaluated
      using Kaplan-Meier, Log-rank test and Cox's proportional hazards as statistical
      methods. Multivariate analysis was used to identify prognostic factors. Median
      follow-up time was 8 years. RESULTS: Anemia before radiochemotherapy was an
      independent prognostic factor for improved DFS (risk ratio 0.76, P=0.04) as well
      as stage, grading, R status (free radial margins), type of surgery,
      carcinoembryonic antigen (CEA) levels, and gender. The univariate analysis
      revealed that anemia was associated with impaired LRS (better local control) but
      with improved DFS. In contrast, hemoglobin decrease during radiotherapy was an
      independent risk factor for DFS (risk ratio 1.97, P=0.04). During radiotherapy,
      only 30.8% of R0-resected patients suffered from hemoglobin decrease compared to
      55.6% if R1/2 resection was performed (P=0.04). The 5-year OAS, CSS, DFS, LRS and
      DRS were 47.0%, 60.0%, 41.4%, 67.2%, and 84.3%, respectively. Significant
      differences between preoperative and postoperative radiochemotherapy were not
      found. CONCLUSION: Anemia before radiochemotherapy and hemoglobin decrease during
      radiotherapy have no predictive value for the outcome of rectal cancer. Stage,
      grading, R status (free radial margins), type of surgery, CEA levels, and gender
      have predictive value for the outcome of rectal cancer.

PMID- 16609991
TI  - Glycine-extended gastrin activates two independent tyrosine-kinases in upstream
      of p85/p110 phosphatidylinositol 3-kinase in human colonic tumour cells.
AB  - AIM: To investigate whether Src, JAK2 and phosphatidylinositol 3-kinase (PI3K)
      pathways are involved in the proliferation of human colonic tumour cells induced
      by glycine-extended gastrin (G-gly), the precursor of the mature amidated gastrin
      and to elucidate the molecular interaction between these three kinases in
      response to this peptide. METHODS: Using the human colonic tumour cell line
      HCT116 as a model, we first measured the activation of PI3K, p60-Src and JAK2 in
      response to G-gly by in vitro kinase assays. Then we investigated the involvement
      of these kinases in G-gly-induced cell proliferation by MTT test. RESULTS: G-gly
      stimulation induced p60-Src, JAK2 and PI3K activation in HCT116. The different
      pathways were involved in proliferation of human colon cancer cells induced by G
      gly. Furthermore, we found that both Src and JAK2 were necessary to PI3K
      regulation by this peptide. However, we did not find any cross-talk between the
      two tyrosine kinases. CONCLUSION: Our results suggest that the p60-Src/PI3K and
      JAK2/PI3K pathways act independently to mediate G-gly proliferative effect on
      human colonic tumour cells.

PMID- 16609992
TI  - Expression of cytokeratins in Helicobacter pylori-associated chronic gastritis of
      adult patients infected with cagA+ strains: an immunohistochemical study.
AB  - AIM: To investigate the expression of different cytokeratins (CKs) in gastric
      epithelium of adult patients with chronic gastritis infected with Helicobacter
      pylori (H pylori) cagA+ strains. METHODS: The expression of CK 7, 8, 18, 19 and
      20 was studied immunohistochemically in antral gastric biopsies of 84 patients.
      All the CKs were immunostained in cagA+H pylori gastritis (57 cases), non-H
      pylori gastritis (17 cases) and normal gastric mucosa (10 cases). RESULTS: In
      cagA+ H pylori gastritis, CK8 was expressed comparably to the normal antral
      mucosa from surface epithelium to deep glands. Distribution of CK18 and CK 19 was
      unchanged, i.e. transmucosal, but intensity of the expression was different in
      foveolar region in comparison to normal gastric mucosa. Cytokeratin 18
      immunoreactivity was significantly higher in the foveolar epithelium of H pylori
      positive gastritis compared to both H pylori-negative gastritis and controls. On
      the contrary, decrease in CK19 immunoreactivity occurred in foveolar epithelium
      of H pylori-positive gastritis. In both normal and inflamed antral mucosa without
      H pylori infection, CK20 was expressed strongly/moderately and homogeneously in
      surface epithelium and upper foveolar region, but in H pylori -induced gastritis
      significant decrease of expression in foveolar region was noted. Generally, in
      both normal antral mucosa and H pylori-negative gastritis, expression of CK7 was
      not observed, while in about half cagA+ H pylori-infected patients, moderate
      focal CK7 immunoreactivity of the neck and coiled gland areas was registered,
      especially in areas with more severe inflammatory infiltrate. CONCLUSION:
      Alterations in expression of CK 7, 18, 19 and 20 together with normal expression
      of CK8 occur in antral mucosa of H pylori-associated chronic gastritis in adult
      patients infected with cagA+ strains. Alterations in different cytokeratins
      expression might contribute to weakening of epithelial tight junctions observed
      in H pylori-infected gastric mucosa.

PMID- 16609993
TI  - Influence of gastric inhibitory polypeptide on pentagastrin-stimulated gastric
      acid secretion in patients with type 2 diabetes and healthy controls.
AB  - AIM: Gastric inhibitory polypeptide is secreted from intestinal K-cells in
      response to nutrient ingestion and acts as an incretin hormone in human
      physiology. While animal experiments suggested a role for GIP as an inhibitor of
      gastric secretion, the GIP effects on gastric acid output in humans are still
      controversial. METHODS: Pentagastrin was administered at an infusion rate of 1
      microg . kg(-1) . h(-1) over 300 min in 8 patients with type 2 diabetes (2
      female, 6 male, 54+/- 10 years, BMI 30.5+/- 2.2 kg/m(2); no history of autonomic
      neuropathy) and 8 healthy subjects (2/6, 46+/- 6 years., 28.9+/- 5.3 kg/m(2)). A
      hyperglycaemic clamp (140 mg/dl) was performed over 240 min. Placebo, GIP at a
      physiological dose (1 pmol . kg(-1) . min(-1)), and GIP at a pharmacological dose
      (4 pmol . kg(-1) . min(-1)) were administered over 60 min each. Boluses of
      placebo, 20 pmol GIP/kg, and 80 pmol GIP/kg were injected intravenously at the
      beginning of each infusion period, respectively. Gastric volume, acid and
      chloride output were analysed in 15-min intervals. Capillary and venous blood
      samples were drawn for the determination of glucose and total GIP. Statistics
      were carried out by repeated-measures ANOVA and one-way ANOVA. RESULTS: Plasma
      glucose concentrations during the hyperglycaemic clamp experiments were not
      different between patients with type 2 diabetes and controls. Steady-state GIP
      plasma levels were 61+/- 8 and 79+/- 12 pmol/l during the low-dose and 327+/- 35
      and 327+/- 17 pmol/l during the high-dose infusion of GIP, in healthy control
      subjects and in patients with type 2 diabetes, respectively (P=0.23 and P=0.99).
      Pentagastrin markedly increased gastric acid and chloride secretion (P< 0.001).
      There were no significant differences in the rates of gastric acid or chloride
      output between the experimental periods with placebo or any dose of GIP. The
      temporal patterns of gastric acid and chloride secretion were similar in patients
      with type 2 diabetes and healthy controls (P=0.86 and P=0.61, respectively).
      CONCLUSION: Pentagastrin-stimulated gastric acid secretion is similar in patients
      with type 2 diabetes and healthy controls. GIP administration does not influence
      gastric acid secretion at physiological or pharmacological plasma levels.
      Therefore, GIP appears to act as an incretin rather than as an enterogastrone in
      human physiology.

PMID- 16609994
TI  - Reconstruction of liver organoid using a bioreactor.
AB  - AIM: To develop the effective technology for reconstruction of a liver organ in
      vitro using a bio-artificial liver. METHODS: We previously reported that a radial
      flow bioreactor (RFB) could provide a three-dimensional high-density culture
      system. We presently reconstructed the liver organoid using a functional human
      hepatocellular carcinoma cell line (FLC-5) as hepatocytes together with mouse
      immortalized sinusoidal endothelial cell (SEC) line M1 and mouse immortalized
      hepatic stellate cell (HSC) line A7 as non parenchymal cells in the RFB. Two x
      10(7) FLC-5 cells were incubated in the RFB. After 5 d, 2 x 10(7) A7 cells were
      added in a similar manner followed by another addition of 10(7) M1 cells 5 d
      later. After three days of perfusion, some cellulose beads with the adherent
      cells were harvested. The last incubation period included perfusion with 200
      nmol/L swinholide A for 2 h and then the remaining cellulose beads along with
      adherent cells were harvested from the RFB. The cell morphology was observed by
      transmission electron microscopy (TEM) and scanning electron microscopy (SEM). To
      assess hepatocyte function, we compared mRNA expression for urea cycle enzymes as
      well as albumin synthesis by FLC-5 in monolayer cultures compared to those of
      single-type cultures and cocultures in the RFB. RESULTS: By transmission electron
      microscopy, FLC-5, M1, and A7 were arranged in relation to the perfusion side in
      a liver-like organization. Structures resembling bile canaliculi were seen
      between FCL-5 cells. Scanning electron microscopy demonstrated fenestrae on SEC
      surfaces. The number of vesiculo-vacuolar organelles (VVO) and fenestrae
      increased when we introduced the actin-binding agent swinholide-A in the RFB for
      2h. With respect to liver function, urea was found in the medium, and expression
      of mRNAs encoding arginosuccinate synthetase and arginase increased when the
      three cell types were cocultured in the RFB. However, albumin synthesis
      decreased. CONCLUSION: Co-culture in the RFB system can dramatically change the
      structure and function of all cell types, including the functional
      characteristics of hepatocytes. Our system proves effective for reconstruction of
      a liver organoid using a bio-artificial liver.

PMID- 16609995
TI  - Interleukin-2 gene-encoded stromal cells inhibit the growth of metastatic
      cholangiocarcinomas.
AB  - AIM: To demonstrate bone marrow stromal cells (BMSCs) can be used as an
      attractive target for genetic modification in the treatment of malignant
      diseases. METHODS: Using a hamster model of biliary cancer, we investigated the
      therapeutic effects of interleukin-2 (IL-2) gene-modified BMSCs. Syrian golden
      hamsters were injected via the femoral vein with 5 x 10(5) cells of the KIGB-5
      biliary cancer cell line (n=20). One week later, the hamsters were injected
      intraperitoneally with BMSCs containing Ad/hIL-2 and Ad/ Delta E1, unmodified
      BMSCs, or RPMI only (control) and observed for 12 wk (n=5 /each group). RESULTS:
      All hamsters treated with BMSCs containing Ad/hIL-2 survived with no evidence of
      the disease during this period. In contrast, hamsters in the other three groups
      showed disseminated metastases involving the lungs as early as 4 wk. CONCLUSION:
      Ad/IL-2 therapy is effective in the treatment of biliary cancer.

PMID- 16609996
TI  - S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte
      cultures by a c-Jun N-terminal kinase activity-independent mechanism.
AB  - AIM: To determine the role of c-Jun N-terminal kinase (JNK) activity in ethanol
      induced apoptosis and the modulation of this signaling cascade by S-Adenosyl
      methionine (AdoMet). METHODS: Primary hepatocyte cultures were pretreated with
      100 micromol/L SP600125, a selective JNK inhibitor, 1 mL/L DMSO or 4 mmol/L
      AdoMet and then exposed to 100 mmo/L ethanol. Hepatocyte apoptosis was determined
      by the TUNEL and DNA ladder assays. JNK activity and its inhibition by SP600125
      and AdoMet were determined by Western blot analysis of c-jun phosphorylation and
      Bid fragmentation. SP600125 and AdoMet effects on the apoptotic signaling pathway
      were determined by Western blot analysis of cytochrome c release and pro-caspase
      3 fragmentation. The AdoMet effect on glutathione levels was measured by Ellman's
      method and reactive oxygen species (ROS) generation by cell cytometry. RESULTS:
      The exposure of hepatocytes to ethanol induced JNK activation, c-jun
      phosphorylation, Bid fragmentation, cytochrome c release and pro-caspase 3
      cleavage; these effects were diminished by SP600125, and caused a significant
      decrease in ethanol-induced apoptosis (P< 0.05). AdoMet exerted an antioxidant
      effect maintaining glutathione levels and decreasing ROS generation, without a
      significant effect on JNK activity, and prevented cytochrome c release and pro
      caspase 3 cleavage. CONCLUSION: The JNK signaling cascade is a key component of
      the proapoptotic signaling pathway induced by ethanol. JNK activation may be
      independent from ROS generation, since AdoMet which exerted antioxidant
      properties did not have a significant effect on JNK activity. JNK pathway
      modulator agents and AdoMet may be components of promising therapies for
      alcoholic liver disease (ALD) treatment.

PMID- 16609997
TI  - Oral administration of S-nitroso-N-acetylcysteine prevents the onset of non
      alcoholic fatty liver disease in rats.
AB  - AIM: To evaluate the potential of S-nitroso-N-acetylcysteine (SNAC) in inhibition
      of lipid peroxidation and the effect of oral SNAC administration in the
      prevention of nonalcoholic fatty liver disease (NAFLD) in an animal model.
      METHODS: NAFLD was induced in Wistar male rats by choline-deficient diet for 4
      wk. SNAC-treated animals (n=6) (1.4 mg/kg per day of SNAC, orally) were compared
      to 2 control groups: one (n=6) received PBS solution and the other (n=6) received
      NAC solution (7 mg/kg per day). Histological variables were semiquantitated with
      respect to macro and microvacuolar fat changes, its zonal distribution, foci of
      necrosis, portal and perivenular fibrosis, and inflammatory infiltrate with zonal
      distribution. LOOHs from samples of liver homogenates were quantified by HPLC.
      Nitrate levels in plasma of portal vein were assessed by chemiluminescence.
      Aqueous low-density lipoprotein (LDL) suspensions (200 microg protein/mL) were
      incubated with CuCl(2) (300 micromol/L) in the absence and presence of SNAC (300
      micromol/L) for 15 h at 37 degree Celsius. Extent of LDL oxidation was assessed
      by fluorimetry. Linoleic acid (LA) (18.8 micromol/L) oxidation was induced by
      soybean lipoxygenase (SLO) (0.056 micromol/L) at 37 degree Celsius in the
      presence and absence of N-acetylcysteine (NAC) and SNAC (56 and 560 micromol/L)
      and monitored at 234 nm. RESULTS: Animals in the control group developed moderate
      macro and microvesicular fatty changes in periportal area. SNAC-treated animals
      displayed only discrete histological alterations with absence of fatty changes
      and did not develop liver steatosis. The absence of NAFLD in the SNAC-treated
      group was positively correlated with a decrease in the concentration of LOOH in
      liver homogenate, compared to the control group (0.7+/-0.2 nmol/mg vs 3.2+/-0.4
      nmol/mg protein, respectively, P<0.05), while serum levels of aminotransferases
      were unaltered. The ability of SNAC in preventing lipid peroxidation was
      confirmed in in vitro experiments using LA and LDL as model substrates.
      CONCLUSION: Oral administration of SNAC prevents the onset of NAFLD in Wistar
      rats fed with choline-deficient diet. This effect is correlated with the ability
      of SNAC to block the propagation of lipid peroxidation in vitro and in vitro.

PMID- 16609998
TI  - Effect of WeiJia on carbon tetrachloride induced chronic liver injury.
AB  - AIM: To study the effect of WeiJia on chronic liver injury using carbon
      tetrachloride (CCl(4)) induced liver injury animal model. METHODS: Wistar rats
      weighing 180-220g were randomly divided into three groups: normal control group
      (Group A), CCl(4) induced liver injury control group (Group B) and CCl(4)
      induction with WeiJia treatment group (Group C). Each group consisted of 14 rats.
      Liver damage and fibrosis was induced by subcutaneous injection with 40% CCl(4)
      in olive oil at 3 mL/kg body weight twice a week for eight weeks for Groups B and
      C rats whereas olive oil was used for Group A rats. Starting from the third week,
      Group C rats also received daily intraperitoneal injection of WeiJia at a dose of
      1.25 microg/kg body weight. Animals were sacrificed at the fifth week (4 male, 3
      female), and eighth week (4 male, 3 female) respectively. Degree of fibrosis were
      measured and serological markers for liver fibrosis and function including
      hyaluronic acid (HA), type IV collagen (CIV), gamma-glutamyl transferase (gamma
      GT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were
      determined. Alpha smooth muscle actin (alpha-SMA) and proliferating cell nuclear
      antigen (PCNA) immunohistochemistry were also performed. RESULTS: CCl(4)
      induction led to the damage of liver and development of fibrosis in Group B and
      Group C rats when compared to Group A rats. The treatment of WeiJia in Group C
      rats could reduce the fibrosis condition significantly compared to Group B rats.
      The effect could be observed after three weeks of treatment and was more obvious
      after eight weeks of treatment. Serum HA, CIV, ALT, AST and gamma-GT levels after
      eight weeks of treatment for Group C rats were 58+/-22 microg/L (P<0.01), 57+/-21
      microg/L (P<0.01), 47+/-10 U/L (P<0.01), 139+/-13 U/L (P<0.05) and 52+/-21 U/L
      (P>0.05) respectively, similar to normal control group (Group A), but
      significantly different from CCl(4) induced liver injury control group (Group B).
      An increase in PCNA and decrease in alpha-SMA expression level was also observed.
      CONCLUSION: WeiJia could improve liver function and reduce liver fibrosis which
      might be through the inhibition of stellate cell activity.

PMID- 16609999
TI  - Effects of interleukin-10 on activation and apoptosis of hepatic stellate cells
      in fibrotic rat liver.
AB  - AIM: To study the effects of interleukin-10 (IL-10) on the expression of alpha
      smooth muscle actin (alpha-SMA), nuclear factor- kappa B(NF- kappa B) and Fas/Fas
      ligand (FasL) in hepatic stellate cells of experimental rats with hepatic
      fibrosis. METHODS: Sixty clean SD rats were randomly divided into control group
      (group N), liver fibrotic group (group C) and IL-10 treatment group (group I).
      Control group received intraperitoneal injection of saline (2 mL/kg), twice a
      week. Fibrotic group was injected intraperitoneally with 50% carbon tetrachloride
      (CCl(4)) (2 mL/kg), twice a week. IL-10 treatment group was given IL-10 at a dose
      of 4 microg/kg 20 minutes before CCl(4) administration from the third week.
      Hepatic stellate cells (HSCs) were isolated from these rats at the seventh and
      eleventh weeks during the course of liver fibrosis, respectively. The expression
      of alpha-SMA and NF- kappa B in HSCs was measured by S-P immunohistochemistry.
      The expression of Fas and FasL mRNA was measured by RT-PCR. Furthermore, liver
      tissues were harvested from three groups at the same time. RESULTS: The CCl(4)-
      induced experimental rat hepatic fibrosis model was established successfully. The
      purity of extracted hepatic stellate cells was about 95% and the yield of hepatic
      stellate cells was 1.2-2.3 x 10(6)/g liver tissue averagely. The positive
      expression of alpha-SMA and NF- kappa B was 36.5% and 28.5% respectively in group
      N. The positive levels of alpha-SMA and NF- kappa B were increased significantly
      in group C compared to group N (P<0.01). The positive signals decreased
      significantly (P<0.05) in group I. In the 11th week, the HSCs of group I became
      round with visible pyknotic nuclei. The expression of NF- kappa B in group C was
      significantly increased in a time-dependent manner (P<0.01), but there was no
      difference in the alpha-SMA expression (P>0.05). The mRNA of Fas and FasL in
      group C was significantly increased in a time-dependent manner compared to that
      in control group. After treated with IL-10, the expression level of Fas and FasL
      was higher in group I than in group C. CONCLUSION: The positive expression of
      alpha-SMA and NF- kappa B in hepatic stellate cells is decreased by ectogenic IL
      10 in liver fibrosis induced by CCl(4). The expression of Fas and FasL is
      increased in the course of liver fibrosis, and is further increased by IL-10. IL
      10 could inhibit the activation of HSCs and cause apoptosis of activated HSCs.

PMID- 16610001
TI  - Ileocecal masses in patients with amebic liver abscess: etiology and management.
AB  - AIM: To assess the causes of ileocecal mass in patients with amebic liver
      abscess. METHODS: Patients with amebic liver abscess and ileocecal mass were
      carefully examined and investigated by contrast-enhanced CT scan followed by
      colonoscopy and histological examination of biopsy materials from lesions during
      colonoscopy. RESULTS: Ileocecal masses were found in seventeen patients with
      amebic liver abscess. The cause of the mass was ameboma in 14 patients, cecal
      tuberculosis in 2 patients and adenocarcinoma of the cecum in 1 patient. Colonic
      ulcers were noted in five of the six (83%) patients with active diarrhea at
      presentation. The ileocecal mass in all these patients was ameboma. Ulcers were
      seen in only one of the 11 (9%) patients without diarrhea. The difference was
      statistically significant from the group with diarrhea (P< 0.005). CONCLUSION:
      Ileocecal mass is not an uncommon finding in patients with amebic liver abscess.
      Although, the ileocecal mass is due to ameboma formation in most cases, it should
      not be assumed that this is the case in all patients. Colonoscopy and
      histological examination of the target biopsies are mandatory to avoid missing a
      more sinister lesion.

PMID- 16610000
TI  - Molecular markers (PECAM-1, ICAM-3, HLA-DR) determine prognosis in primary non
      Hodgkin's gastric lymphoma patients.
AB  - AIM: To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR
      antigens in patients with primary non-Hodgkin's gastric lymphoma. METHODS: We
      immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36
      B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten
      healthy gastric tissue specimens were used as controls. Clinicopathological and
      survival data were correlated with the staining results. RESULTS: HLA-DR antigen
      expression was detected in 33 gastric lymphoma patients (91.7%) and 6 non
      malignant patients (54.5%). PECAM-1 stained tumor cells of 10 patients (27.8%),
      endothelial cells of 9 patients (25%) and inflammatory infiltrate of 4 patients
      (40%) with benign gastric disease. ICAM-3 expression was observed on the tumor
      cells of 17 patients (47.2%), while 5 non-malignant patients (50%) were stained
      positive as well. None of the healthy controls was stained for any of the genes
      studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to
      be statistically significant independent prognostic factors associated with a
      favourable and an unfavourable prognosis respectively (P=0.009 and P=0.003). In
      the univariate analysis, PECAM-1(+)/ICAM-3(-) and HLA-DR(-)/ICAM-3(-) patients
      exhibited a significantly decreased overall survival compared to those with the
      exactly opposite gene expression patterns (P=0.0041 and P=0.0091, respectively).
      Those patients who were HLA-DR(+)/ICAM-3(+)/PECAM-1(-) (n=8) had a significantly
      higher survival rate compared to the rest of the group (n=24) (P=0.0289).
      CONCLUSION: PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor
      expansion potential and host immune surveillance respectively. Their combined use
      may help us to identify high-risk patients who could benefit from more aggressive
      therapeutic protocols.

PMID- 16610002
TI  - Up-regulation of NAD(P)H quinone oxidoreductase 1 during human liver injury.
AB  - AIM: To investigate the expression and activity of NAD(P)H quinone oxidoreductase
      1 (NQO1) in human liver specimens obtained from patients with liver damage due to
      acetaminophen (APAP) overdose or primary biliary cirrhosis (PBC). METHODS: NQO1
      activity was determined in cytosol from normal, APAP and PBC liver specimens.
      Western blot and immunohistochemical staining were used to determine patterns of
      NQO1 expression using a specific antibody against NQO1. RESULTS: NQO1 protein was
      very low in normal human livers. In both APAP and PBC livers, there was strong
      induction of NQO1 protein levels on Western blot. Correspondingly, significant up
      regulation of enzyme activity (16- and 22-fold, P< 0.05) was also observed in
      APAP and PBC livers, respectively. Immunohistochemical analysis highlighted
      injury-specific patterns of NQO1 staining in both APAP and PBC livers.
      CONCLUSION: These data demonstrate that NQO1 protein and activity are markedly
      induced in human livers during both APAP overdose and PBC. Up-regulation of this
      cytoprotective enzyme may represent an adaptive stress response to limit further
      disease progression by detoxifying reactive species.

PMID- 16610003
TI  - Giardia lamblia infection in patients with irritable bowel syndrome and
      dyspepsia: a prospective study.
AB  - AIM: To evaluate the prevalence of Giardia lamblia (G. lamblia) infection in
      patients with irritable bowel syndrome (IBS) and dyspepsia and to establish which
      is the most accurate test to diagnose the infection in this setting. METHODS: One
      hundred and thirty-seven patients who consecutively attended the Outpatient
      Gastroenterology Clinic for the first time between January 2002 and December 2003
      due to symptoms of IBS and/or dyspepsia were recruited. All patients underwent
      clinical evaluation, first-step haematology and chemistry tests, serologic assays
      for celiac disease, lactose-H(2) breath test, abdominal ultrasonography, and
      esophagogastroduodenoscopy. Helicobacter pylori status was evaluated. In patients
      with symptoms of IBS older than 45 years, colonoscopy was also performed. In all
      patients, duodenal biopsies and stool samples were examined for trophozoites and
      cysts of G. lamblia by several methods. RESULTS: G. lamblia was identified in 9
      patients. The following diagnoses were also made: IBS (100/137, 73%), functional
      dyspepsia (62/137, 45%), organic dyspepsia (33/137, 24%), and lactose intolerance
      (75/137, 55%). A significant association was found between giardiasis and H
      pylori infection (c2=6.632, OR=12.4, CI=1.5-68.1). There were no symptoms that
      reliably allowed the recognition of giardiasis. Direct search of the parasite in
      duodenal biopsy and stool sample examinations gave concordant results in all
      cases while histological examination of duodenal biopsies displayed a low
      sensitivity (e.g., 22.2%). CONCLUSION: In this consecutive series, diagnosis of
      G. lamblia infection accounted for 6.5% of patients with IBS and dyspepsia.
      Duodenal biopsies for diagnosis of giardiasis may be unnecessary if stool sample
      examination is performed.

PMID- 16610004
TI  - Clinical characteristics of a group of adults with nodular lymphoid hyperplasia:
      a single center experience.
AB  - AIM: To describe the clinical and histological characteristics of a group of
      adults with small-bowel nodular lymphoid hyperplasia (NLH). METHODS: Patients
      were searched for five years in pathology records of our institution. The biopsy
      material was reassessed using strict histopathological criteria. Clinical data
      were obtained from medical records. RESULTS: Small-bowel NLH was diagnosed in 18
      cases. The female: male ratio was 2:1. The most frequent symptoms were diarrhea
      (72%), involuntary weight loss (72%) and abdominal pain (61%). Nine patients
      (50%) had immunodeficiency. Small-bowel bacterial overgrowth was found in three
      (17%) cases. At small-bowel NLH diagnosis, three (17%) had associated lymphoma:
      two intestinal and one extra-intestinal lymphomas. In two patients with villous
      atrophy and anti-endomysial antibodies the diagnosis of celiac disease was
      established. Giardia lamblia infection was found in only one patient with
      hypogammaglobulinemia (Herman's syndrome). CONCLUSIONS: NLH is uncommon in adult
      patients. Associated diseases are immunodeficiency and lymphoid tissue
      malignancies.

PMID- 16610005
TI  - Hyperlactatemia in patients with non-acetaminophen-related acute liver failure.
AB  - AIM: To characterize hyperlactatemia in patients with non-acetaminophen acute
      liver failure (ALF) in an attempt to clarify the mechanisms implicated and the
      role as a prognosis factor. METHODS: In the setting of liver transplantation, 63
      consecutive patients with non-acetaminophen acute liver failure were studied in
      relation to tissue oxygenation, hemodynamic and metabolic parameters. Before and
      after transplantation, the number of infected patients and outcome were
      registered. RESULTS: Acute ALF showed higher levels of lactate than subacute ALF
      (5.4+/- 1 mmol/L versus 2.2+/- 0.6 mmol/L, P=0.01). Oxygenation parameters were
      within the normal range. Lactate levels showed good correlation with respiratory
      quotient (r=0.759, P< 0.005), mean glucose administration (r=0.664, P=0.01) and
      encephalopathy (r=0.698, P=0.02), but not with splanchnic arteriovenous
      difference in PCO2, pH and the presence of infection (P=0.1). Portal vein lactate
      was higher (P< 0.05) than arterial and mixed venous lactate, suggesting its
      production of hyperlactatemia in the intestine and spleen. The presence of
      infection was an independent predictor of survival. CONCLUSION: Hyperlactatemia
      is not a prognosis factor due to byproduct of the overall acceleration in
      glycolysis.

PMID- 16610006
TI  - Clinical features of hepatopulmonary syndrome in cirrhotic patients.
AB  - AIM: To evaluate the frequency, clinical and paraclinical features of
      hepatopulmonary syndrome (HPS) and to determine their predictive values in
      diagnosis of this syndrome in patients in Iran. METHODS: Fifty four cirrhotic
      patients underwent contrast enhanced echocardiography to detect intrapulmonary
      and intracardiac shunts by two cardiologists. Arterial blood oxygen, O(2)
      gradient (A-a) and orthodoxy were measured by arterial blood gas (ABG) test. The
      patients positive for diagnostic criteria of HPS were defined as clinical HPS
      cases and those manifesting the intrapulmonary arterial dilation but no other
      criteria (arterial blood hypoxemia) were defined as lHPS cases. HPS frequency,
      sensitivity, positive and negative predictive values of clinical and paraclinical
      features were studied. RESULTS: Ten (18.5%) and seven (13%) cases had clinical
      and subclinical HPS, respectively. The most common etiology was hepatitis B.
      Dyspnea (100%) and cyanosis (90%) were the most prevalent clinical features.
      Dyspnea and clubbing were the most sensitive and specific clinical features
      respectively. No significant relationship was found between HPS and splenomegaly,
      ascites, edema, jaundice, oliguria, and collateral veins. HPS was more prevalent
      in hepatitis B. PaO(2)< 70 and arterial-alveolar gradient had the highest
      sensitivity in HPS patients. Orthodoxy specificity was 100%. CONCLUSION: Clubbing
      with positive predictive value (PPV) of 75% and dyspnea with negative predictive
      value (NPV) of 75% are the best clinical factors in diagnosis of HPS syndrome.
      PaO(2)< 70 and P (A-a) O(2)> 30 and their sum, are the most valuable negative and
      positive predictive values in HPS patients.

PMID- 16610007
TI  - Seroprevalence of Helicobacter pylori in dyspeptic patients and its relationship
      with HIV infection, ABO blood groups and life style in a university hospital,
      Northwest Ethiopia.
AB  - AIM: To determine the prevalence of Helicobacter pylori (H pylori) among
      dyspeptic patients and to assess the relationship between H pylori infection,
      blood group, HIV infection and life style of the patients. METHODS: In a hospital
      based cross-sectional study, patients attending Outpatient Department of
      University of Gondar Hospital were enrolled. Socio-demographic information was
      collected using questionnaires. Serum was analyzed for anti-H pylori IgG
      antibodies using a commercial kit. HIV serostatus was determined by enzyme-linked
      immunosorbent assay (ELISA). Blood grouping was performed by slide agglutination
      tests. RESULTS: A total of 215 dyspeptic patients were included in the study. One
      hundred and sixteen patients (54%) were females and 99 (46%) were males. Anti-H
      pylori IgG antibodies were detected in sera of 184 (85.6%) patients. The
      prevalence was significantly higher in patients aged 50 years and above. Twenty
      point five percent of the patients were found to be seropositive for HIV. No
      significant association was found between sex, ABO blood groups, consumption of
      spicy diets, socio-economic status and seropositivity for H pylori. However,
      alcohol consumption was significantly associated with H pylori serology.
      CONCLUSION: The prevalence of H pylori infection is associated with a history of
      alcohol intake and older age. The effect of different diet, alcohol and
      socioeconomic status as risk factors for H pylori infection needs further study.

PMID- 16610008
TI  - Effect of electroacupunture on gastric mucosal intestinal trefoil factor gene
      expression of stress-induced gastric mucosal injury in rats.
AB  - AIM: To investigate electroacupuncture(EA) at the acupoints of Stomach Meridian
      of Foot-Yangming (SMFY), Gallbladder Meridian of Foot-Yangming (SMFY) on gastric
      mucosal intestinal trefoil factor (ITF) gene expression detection in stress
      induced rats with gastric mucosal lesion, and to explore the regulatory mechanism
      and significance of EA-related gastric mucosal protective effect. METHODS: Forty
      rats were randomly divided into 4 groups: Blank group, Model group, Model
      group+EA at acupoints of SMFY group ("SMFY group"), and Model group+EA at
      acupoints of GMFY group(GMFY group). All rats (except blank group) were made
      model by water immersion and restraint stress (WRS). Then the gastric mucosa
      tissue in each rat was taken off after assessment of gastric mucosal lesion
      index(GUI), and the expression of ITF mRNA of the tissues was detected by reverse
      transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Compared with
      Model group(54.3+/- 1.34), the GUI value in SMFY group (31+/- 2.21) decreased
      significantly(P< 0.01), so did that in GMFY group (39.8+/- 1.62, P< 0.05),
      meanwhile GUI value in SMFY group was significantly lower than in GMFY group(P<
      0.01). Compared with Model group (0.65+/- 0.01), EA had a tendency to improve the
      expression of gastric mucosal ITFmRNA gene: such tendency existed in GMFY group
      (0.66+/- 0.01) but with no significant difference(P>0.05), in SMFY group(0.76+/-
      0.01) with an extremely obvious difference (P< 0.01), furthermore the expression
      in SMFY group was significantly higher than in GMFY group (P< 0.01). CONCLUSION:
      The gastric mucosal protective effect by EA at the acupoints of SMFY and GMFY was
      related to the expression variance of ITF, indicating certain meridian
      specificity exists. It could be one proof for the TCM theory "Relative
      particularity between SMFY and stomach".

PMID- 16610009
TI  - Large Brunner's gland adenoma: case report and literature review.
AB  - Brunner's gland adenoma (BGA) is a very rare benign tumour of the duodenum, which
      is usually asymptomatic and discovered incidentally at endoscopy. Occasionally,
      this lesion may be large, causing upper gastrointestinal haemorrhage or
      intestinal obstruction. The case had a large Brunner's gland adenoma, presenting
      melena that was managed by endoscopic excision.

PMID- 16610010
TI  - Metastasis of hepatocellular carcinoma to the small bowel manifested by
      intussusception.
AB  - Hepatocellular carcinoma (HCC) is a highly invasive tumor that metastasizes
      hematogenously and lymphogenously to distant site. Frequent sites are lung,
      regional lymph node, bone, and adrenal gland. But metastasis to the
      gastrointestinal (GI) tract is rare, and most common site is stomach. Metastasis
      to the small intestine is extremely rare. Moreover, metastatic HCC of the small
      bowel causing intussusception has not been reported until now. Here, we report a
      case of metastasis of HCC to the small bowel manifested by intussusception.

PMID- 16610011
TI  - Patient with hepatocellular carcinoma related to prior acute arsenic intoxication
      and occult HBV: epidemiological, clinical and therapeutic results after 14 years
      of follow-up.
AB  - Little is known about the long-term survivors of acute arsenic intoxication. We
      present here a clinical case report of a man with chronic hepatitis B virus (HBV)
      infection who developed hepatocellular carcinoma four years after acute arsenic
      poisoning. HBsAg was detected in serum in 1990 when he voluntarily donated blood.
      In 1991, the patient suffered from severe psychological depression that led him
      to attempt suicide by massive ingestion of an arsenic-containing rodenticide. He
      survived with polyneuropathy and paralysis of the lower limbs, and has been
      wheelchair-bound since then. During participation in a follow-up study conducted
      among HBV carriers, abdominal ultrasound detected a two-centimeter liver mass
      consistent with hepatocellular carcinoma. The tumor was confirmed by computed
      tomography (CT) and magnetic resonance image (MRI). Because of his significant
      comorbidity, the patient received palliative treatment with transarterial
      lipiodol chemoembolization (TACE) on three occasions (1996, 1997 and 1999). At
      his most recent visit in May 2005, the patient was asymptomatic, liver enzymes
      were normal and the tumor was in remission on ultrasound.

PMID- 16610012
TI  - Mucinous cystadenoma of the appendix associated with adenocarcinoma of the
      sigmoid colon and hepatocellular carcinoma of the liver: report of a case.
AB  - Mucinous cystadenoma of the appendix is a rare condition and represents one of
      the three entities with the common name mucocele of the appendix. It is
      characterized by a cystic dilatation of the lumen with stasis of mucus inside it.
      Histopathologically mucocele is divided into three groups: focal or diffuse
      mucosal hyperplasia, mucinous cystadenoma and mucinous cystadenocarcinoma. This
      condition is often associated with other neoplasia, especially adenocarcinoma of
      the colon and ovaries. We here describe a 57 year old male patient who presented
      with abdominal discomfort, constipation, fresh blood in stool and frequent
      urination. He had a big cystadenoma of the appendix associated with
      adenocarcinoma of the colon and hepatocellular carcinoma of the liver. The
      patient underwent right haemicolectomy, sigmoid colon resection and segmental
      resection of the liver. Now 3 years later he has no evidence of disease relapse.
      According to this, we stress the need of accurate preoperative diagnosis and
      intraoperative exploration of the whole abdomen in these patients.

PMID- 16610013
TI  - Cytomegalovirus gastritis after rituximab treatment in a non-Hodgkn's lymphoma
      patient.

PMID- 16610014
TI  - Role of Toll-like receptors in health and diseases of gastrointestinal tract.
AB  - The human gastrointestinal (GI) tract is colonized by non-pathogenic commensal
      microflora and frequently exposed to many pathogenic organisms. For the
      maintenance of GI homeostasis, the host must discriminate between pathogenic and
      non-pathogenic organisms and initiate effective and appropriate immune and
      inflammatory responses. Mammalian toll-like receptors (TLRs) are members of the
      pattern-recognition receptor (PRR) family that plays a central role in the
      initiation of innate cellular immune responses and the subsequent adaptive immune
      responses to microbial pathogens. Recent studies have shown that gastrointestinal
      epithelial cells express almost all TLR subtypes characterized to date and that
      the expression and activation of TLRs in the GI tract are tightly and
      coordinately regulated. This review summarizes the current understanding of the
      crucial dual roles of TLRs in the development of host innate and adaptive immune
      responses to GI infections and the maintenance of the immune tolerance to
      commensal bacteria through down-regulation of surface expression of TLRs in
      intestinal epithelial cells.

PMID- 16610015
TI  - Treatment of nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated
      liver enzymes in the developed nations. Beyond prevention programs which are of
      particular interest because of the increasing number of overweight children,
      treatment should be focussed on the most important risk factors, obesity and
      insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD,
      the number of potential therapeutic options increased. However, many studies
      investigating the therapeutic effect show shortcomings in at least one of the
      following points: lack of a serial liver biopsy, short term of treatment and
      limited number of included patients. The second generation insulin sensitizer
      pioglitazone and rosiglitazone show the most promising improvements in NAFLD, but
      weight gain and potential hepatotoxicity calls for attention. In conclusion, a
      general recommendation for the application of specific drugs cannot be given.
      Besides controlled clinical trials, weight reduction and physical activity to
      improve insulin sensitivity in obese patients should be the priority objective.

PMID- 16610016
TI  - Mechanisms inactivating the gene for E-cadherin in sporadic gastric carcinomas.
AB  - AIM: To study the role of CDH1/E-cadherin (E-cad) gene alteration profiles
      including mutation, loss of heterozygosity (LOH), promoter polymorphism and
      hypermethylation in mechanisms of CDH1 inactivation in gastric carcinoma (GC).
      METHODS: Specimens were collected surgically from 70 patients with GC.
      Allelotyping PCR and detection of LOH, denaturing high pressure liquid
      chromatography and DNA sequencing, restriction fragment length polymorphism
      analysis, methylation specific PCR, and immunohistochemical staining were used.
      RESULTS: Promoter polymorphism was not a major mechanism of E-cad inactivation.
      Only one truncating mutation was found in a diffuse type tumor (3%). Both LOH and
      promoter hypermethylation were major mechanisms of E-cad inactivation, but
      interestingly, there was a negative association between the fraction of allelic
      loss (LOH) in tumors and hypermethylation of CDH1. Therefore LOH and
      hypermethylation were two different tumorigenic pathways involved in GC.
      CONCLUSION: Given the findings that somatic mutation was extremely low and the
      relationship between LOH and hypermethylation was inverse, any two combinations
      of these three factors cannot fulfill the classical two-hit hypothesis of CDH1
      inactivation. Thus, other mechanisms operating at the transcriptional level or at
      the post-translational level might be required to induce E-cadherin inactivation.

PMID- 16610017
TI  - Effect of NaCl and Helicobacter pylori vacuolating cytotoxin on cytokine
      expression and viability.
AB  - AIM: To determine whether Helicobacter pylori (H pylori) vacuolating cytotoxin
      (VacA) regulates release of pro-inflammatory cytokines (IL-1beta, IL-8, TNF
      alpha, and IL-6) or alters gastric epithelial cell viability and to determine
      whether NaCl affects these VacA-induced changes. METHODS: Vacuolating activity
      was determined by measuring the uptake of neutral red into vacuoles of VacA
      treated human gastric epithelial (AGS) cells. AGS cell viability was assessed by
      direct cell counting. Specific enzyme-linked immunosorbent assays (ELISA) and
      reverse transcriptase-polymerase chain reaction(RT-PCR) were performed to examine
      the effects of H pylori VacA and NaCl on cell pro-inflammatory cytokine
      production in AGS cells. Immunohistochemical staining of gastric tissue from
      Mongolian gerbils was used to confirm VacA-induced pro-inflammatory cytokine
      production and the effects of NaCl on this VacA-induced response. RESULTS:
      Addition of VacA alone reduced AGS cell viability (P < 0.05), and this reduction
      was enhanced by high doses of NaCl (P < 0.05). VacA alone induced expression of
      TNF-alpha, IL-8 and IL-1beta, while NaCl alone induced expression of TNF-alpha
      and IL-1beta. Changes in mRNA levels in the presence of both VacA and NaCl were
      more complicated. For the case of TNF-alpha, expression was dose-dependent on
      NaCl. IL-6 mRNA was not detected. However, low levels of IL-6 were detected by
      ELISA. Positive immunohistochemical staining of IL-1, IL-6, and TNF-alpha was
      found in gastric tissue of H pylori-infected gerbils fed with either a normal
      diet or a high salt diet. However, the staining of these three cytokines was
      stronger in H pylori-infected animals fed with a 5 g/kg NaCl diet. CONCLUSION:
      VacA decreases the viability of AGS cells, and this effect can be enhanced by
      NaCl. NaCl also affects the production of pro-inflammatory cytokines induced by
      VacA, suggesting that NaCl plays an important role in H pylori-induced gastric
      epithelial cell cytotoxicity.

PMID- 16610018
TI  - Helicobacter pylori and other Helicobacter species DNA in human bile samples from
      patients with various hepato-biliary diseases.
AB  - AIM: To investigate the presence of Helicobacter species by nested PCR of 16S
      rRNA genes followed by the presence of Helicobacter pylori (H pylori) 16S rRNA,
      ureA, cagA genes in bile obtained at endoscopic retrograde cholangio
      pancreatography (ERCP) from 60 Indian subjects. METHODS: Sixty bile samples were
      obtained from patients diagnosed with various hepato-biliary diseases and control
      subjects at ERCP. PCR analysis was carried out using primers for Helicobacter
      genus 16S rRNA gene and H pylori (16S rRNA, ureA and cagA) genes. Gastric H
      pylori status was also assessed from biopsies obtained at endoscopy from patients
      with various hepato-biliary diseases and controls. The control group mainly
      consisted of subjects with gastric disorders. Sequencing analysis was performed
      to confirm that PCR products with 16S rRNA and cagA primers were derived from H
      pylori. RESULTS No Helicobacters were grown in culture from the bile samples.
      Helicobacter DNA was detected in bile of 96.7% and 6.6% of groups I and II
      respectively. Ten from group I were positive for 16S rRNA and ureA and 9 were
      positive for cagA gene. In contrast of the 2 from the control, 1 amplified with
      16S rRNA, ureA and cagA primers used. The sequences of the 16S rRNA genes and
      cagA were 99% similar to Helicobacter pylori. CONCLUSION: Helicobacters are
      associated with the pathogenesis of various hepato-biliary disorders.

PMID- 16610019
TI  - Liver fibrosis and tissue architectural change measurement using fractal
      rectified metrics and Hurst's exponent.
AB  - AIM: To provide the accurate alternative metrical means of monitoring the effects
      of new antiviral drugs on the reversal of newly formed collagen. METHODS:
      Digitized histological biopsy sections taken from 209 patients with chronic C
      virus hepatitis with different grade of fibrosis or cirrhosis, were measured by
      means of a new, rapid, user-friendly, fully computer-aided method based on the
      international system meter rectified using fractal principles. RESULTS: The
      following were described: geometric perimeter, area and wrinkledness of fibrosis;
      the collation of the Knodell, Sheuer, Ishak and METAVIR scores with fractal
      rectified metric measurements; the meaning of the physical composition of
      fibrosis in relation to the magnitude of collagen islets; the intra- and inter
      biopsy sample variability of these parameters; the"staging" of biopsy sections
      indicating the pathway covered by fibrosis formation towards its maximum known
      value; the quantitative liver tissue architectural changes with the Hurst
      exponent. CONCLUSION: Our model provides the first metrical evaluations of the
      geometric properties of fibrosis and the quantitative architectural changes of
      the liver tissue. The representativeness of histological sections of the whole
      liver is also discussed in the light of the results obtained with the Hurst
      coefficient.

PMID- 16610020
TI  - Comparison of protocatechuic aldchyde in Radix Salvia miltiorrhiza and
      corresponding pharmacological sera from normal and fibrotic rats by high
      performance liquid chromatography.
AB  - AIM: To observe the effect of protocatechuic aldchyde on the proliferation of
      hepatic stellate cells (HSCs). METHODS: Liver fibrosis was induced in rats by
      carbon tetrachloride (CCl4). Then normal and fibrotic drug sera were extracted
      from rats. The effects of protocatechuic aldchyde, raw Radix Salvia miltiorrhiza
      and drug sera of Salvia miltiorrhiza on HSC growth were determined by CCK-8. The
      protocatechuic aldchyde was separated by high performance liquid chromatography
      (HPLC) in a Alltima C18 column (250 mm mult 4.6 mm, 5 microm) with a mobile phase
      of acetonitrile-4% glacial acetic acid solution (gradient elution) at the
      wavelength of 281 nm. RESULTS: Protocatechuic aldchyde, raw Radix Salvia
      miltiorrhiza and drug sera of Salvia miltiorrhiza were found to have inhibitory
      effects on proliferation of rat HSCs. Raw Radix Salvia miltiorrhiza had a
      stronger inhibitory effect than the drug sera. The fibrotic drug sera showed a
      higher suppressive effect than the normal drug sera (P < 0.05). Protocatechuic
      aldchyde was found in crude materials of both Radix Salvia miltiorrhiza and its
      corresponding drug sera. The average recovery (n = 6) was 110.5% for raw Salvia
      miltiorrhiza Bge, 102% for normal drug sera and 105.2% for fibrotic drug sera.
      The relative standard devitation (RSD) was 0.37%, 1.96% and 1.51%, respectively
      (n = 6). The contents of protocatechuic aldchyde were 0.22%, 0.15% and 0.19%,
      respectively (n = 6) (P < 0.05). The RSD was 0.33%, 0.75% and 1.24% (n = 6) for
      raw material of Radix Salvia miltiorrhiza, normal drug sera and fibrotic drug
      sera, respectively. The samples were stable for 6 d. CONCLUSION: Protocatechuic
      aldchyde can inhibit the growth of HSCs. HPLC is suitable for the determination
      of virtual bioactive components of Chinese herbal medicines in vitro.

PMID- 16610021
TI  - Treatment of active steroid-refractory inflammatory bowel diseases with
      granulocytapheresis: Our experience with a prospective study.
AB  - AIM: To report our experience with the use of granulocytapheresis (GCAP) in 14
      patients with active steroid-refractory inflammatory bowel disease (IBD) in order
      to evaluate its efficacy in achieving remission and maintaining a long lasting
      symptom-free period. METHODS: The activity of the disease was evaluated by
      clinical activity index (CAI) and endoscopic index (EI) in ulcerative colitis
      (UC), while by Crohn's disease activity index (CDAI) in Crohn's disease (CD). The
      patients were treated using the Adacolumn system, an adsorption column which
      selectively binds to granulocytes and monocytes. One session/week of GCAP was
      performed for 5 wk. Steroids were stopped during apheresis. RESULTS: All the
      patients completed the five-week course showing no complications. At the end of
      the last session, 93% of patients showed a clinical remission of the disease that
      persisted for 6 mo. Nine months after the end of the treatment, 60% of the cases
      maintained remission, while 23% of the patients were still in clinical remission
      after 12 mo. CONCLUSION: Even if the number of our patients with steroid
      refractory IBDs was not big, we can assert that GCAP is well tolerated and
      effective, especially in the first six months after the treatment, in a
      significant percentage of cases. The rate of sustained response drops slightly
      after 6 mo and significantly after 12 mo, however the absence of severe side
      effects can be a stimulus for further evaluating new schedules of treatment.

PMID- 16610022
TI  - Echo-enhanced ultrasound with pulse inversion imaging: A new imaging modality for
      the differentiation of cystic pancreatic tumours.
AB  - AIM: To describe and discuss echo-enhanced sonography in the differential
      diagnosis of cystic pancreatic lesions. METHODS: The pulse inversion technique
      (with intravenous injection of 2.4 mL SonoVue) or the power-Doppler mode under
      the conditions of the 2nd harmonic imaging (with intravenous injection of 4 g
      Levovist) was used for echo-enhanced sonography. RESULTS: Cystadenomas frequently
      showed many vessels along fibrotic strands. On the other hand,
      cystadenocarcinomas were poorly and chaotically vascularized. "Young pseudocysts"
      were frequently found to have a highly vascularised wall. However, the wall of
      the "old pseudocysts" was poorly vascularized. Data from prospective studies
      demonstrated that based on these imaging criteria the sensitivities and
      specificities of echo-enhanced sonography in the differentiation of cystic
      pancreatic masses were >90%. CONCLUSION: Cystic pancreatic masses have a
      different vascularization pattern at echo-enhanced sonography. These
      characteristics are useful for their differential diagnosis, but histology is
      still the gold standard.

PMID- 16610023
TI  - Surgical anatomy of the innervation of pylorus in human and Suncus murinus, in
      relation to surgical technique for pylorus-preserving pancreaticoduodenectomy.
AB  - AIM: To clarify the innervation of the antro-pyloric region in humans from a
      clinico-anatomical perspective. METHODS: The stomach, duodenum and surrounding
      structures were dissected in 10 cadavers, and immersed in a 10mg/L solution of
      alizarin red S in ethanol to stain the peripheral nerves. The distribution
      details were studied to confirm innervations in the above areas using a binocular
      microscope. Similarly, innervations in 10 Suncus murinus were examined using the
      method of whole-mount immunohistochemistry. RESULTS: The innervation of the
      pyloric region in humans involved three routes: One arose from the anterior
      hepatic plexus via the route of the suprapyloric/supraduodenal branch of the
      right gastric artery; the second arose from the anterior and posterior gastric
      divisions, and the third originated from the posterior-lower region of the
      pyloric region, which passed via the infrapyloric artery or retroduodenal
      branches and was related to the gastroduodenal artery and right gastroepiploic
      artery. For Suncus murinus, results similar to those in humans were observed.
      CONCLUSION: There are three routes of innervation of the pyloric region in
      humans, wherein the route of the right gastric artery is most important for
      preserving pyloric region innervation. Function will be preserved by more than
      80% by preserving the artery in pylorus-preserving pancreaticoduodenectomy
      (PPPD). However, the route of the infrapyloric artery should not be disregarded.
      This route is related to several arteries (the right gastroepiploic and
      gastroduodenal arteries), and the preserving of these arteries is advantageous
      for preserving pyloric innervation in PPPD. Concurrently, the nerves of Latarjet
      also play an important role in maintaining innervation of the antro-pyloric
      region in PPPD. This is why pyloric function is not damaged in some patients when
      the right gastric artery is dissected or damaged in PPPD.

PMID- 16610024
TI  - Estimating liver weight of adults by body weight and gender.
AB  - AIM: To estimate the standard liver weight for assessing adequacies of graft size
      in live donor liver transplantation and remnant liver in major hepatectomy for
      cancer. METHODS: In this study, anthropometric data of body weight and body
      height were tested for a correlation with liver weight in 159 live liver donors
      who underwent donor right hepatectomy including the middle hepatic vein. Liver
      weights were calculated from the right lobe graft weight obtained at the back
      table, divided by the proportion of the right lobe on the computed tomography.
      RESULTS: The subjects, all Chinese, had a mean age of 35.8+/-10.5 years, and a
      female to male ratio of 118:41. The mean volume of the right lobe was 710.14+/
      131.46 mL and occupied 64.55%+/-4.47% of the whole liver on computed tomography.
      Right lobe weighed 598.90+/-117.39 g and the estimated liver weight was 927.54+/
      168.78 g. When body weight and body height were subjected to multiple stepwise
      linear regression analysis, body height was found to be insignificant. Females of
      the same body weight had a slightly lower liver weight. A formula based on body
      weight and gender was derived: Estimated standard liver weight (g) = 218 + BW
      (kg) x 12.3 + gender x 51 (R2 = 0.48) (female = 0, male = 1). Based on the
      anthropometric data of these 159 subjects, liver weights were calculated using
      previously published formulae derived from studies on Caucasian, Japanese,
      Korean, and Chinese. All formulae overestimated liver weights compared to this
      formula. The Japanese formula overestimated the estimated standard liver weight
      (ESLW) for adults less than 60 kg. CONCLUSION: A formula applicable to Chinese
      males and females is available. A formula for individual races appears necessary.

PMID- 16610025
TI  - Gastrointestinal stromal tumors in a cohort of Chinese patients in Hong Kong.
AB  - AIM: To investigate the prevalence and clinical pattern of gastrointestinal
      stromal tumors (GISTs) in Hong Kong Chinese, and to assess the impact of
      introduction of CD117 on the disease incidence. METHODS: From the database of the
      Department of Pathology of Yan Chai Hospital, 47 patients, with GISTs from
      September 1995 to December 2003 were included in this study. Ten GISTs were
      diagnosed before the introduction of CD117. The clinical features, tumor
      characteristics, and treatment were analyzed. Factors predicting tumor related
      death or recurrence were studied with Cox proportional hazard model. RESULTS: The
      patients included 26 males and 21 females, with a mean age of 66.6 years (SD
      13.1, range 29-87 years). The estimated prevalence of GISTs was 13.4-15.6 per
      100,000 people, with an annual incidence of 1.68-1.96 per 100,000 people. The
      annual incidence of GISTs before and after the introduction of CD117 was 1.1 per
      100,000 people and 2.1 per 100,000 people respectively. Stomach (34 patients,
      72.3%) was the most common location for the tumor, followed by the small
      intestine (8 patients, 17.0%), esophagus (2 patients, 4.3%), omentum (2 patients,
      4.3%) and colon (1 patient, 2.1%). Thirty-one patients (66%) had complete tumor
      resection. Eleven out of 16 deaths (23%) were tumor-related. The median survival
      time was 26 mo. Five-year survival rate was 61.3%. The significant factors
      associated with tumor-related death or recurrence were incomplete resection,
      tumor size 5 cm or above, invasion to the adjacent organ or presence of
      metastasis. CONCLUSION: The incidence of GIST in Hong Kong is comparable to that
      in the United States but lower than that in Finland. The true incidence of GISTs
      could be underestimated before the introduction of CD117. Incomplete resection,
      tumor size 5 cm or above, invasion to the adjacent organ or presence of
      metastasis are factors predicting tumor-related death or recurrence.

PMID- 16610026
TI  - Establishment of risk model for pancreatic cancer in Chinese Han population.
AB  - AIM: To investigate risk factors for pancreatic cancer and establish a risk model
      for Han population. METHODS: This population-based case-control study was carried
      out from January 2002 to April 2004. One hundred and nineteen pancreatic cancer
      patients and 238 healthy people completed the questionnaire which was used for
      risk factor analysis. Logistic regression analysis was used to calculate odds
      ratio (ORs), 95% confidence intervals (Cls) and beta value, which were further
      used to establish the risk model. RESULTS: According to the study, people who
      have smoked more than 17 pack-years had a higher risk to develop pancreatic
      cancer compared to non-smokers or light smokers (not more than 17 pack-years) (OR
      1.98; 95% CI 1.11-3.49, P = 0.017). More importantly, heavy smokers in men had
      increased risk for developing pancreatic cancer (OR 2.11; 95%CI 1.18-3.78, P =
      0.012) than women. Heavy alcohol drinkers (>20 cup-years) had increased risk for
      pancreatic cancer (OR 3.68; 95%CI 1.60-8.44). Daily diet with high meat intake
      was also linked to pancreatic cancer. Moreover, 18.5% of the pancreatic cancer
      patients had diabetes mellitus compared to the control group of 5.8% (P =
      0.0003). Typical symptoms of pancreatic cancer were anorexia, upper abdominal
      pain, bloating, jaundice and weight loss. Each risk factor was assigned a value
      to represent its importance associated with pancreatic cancer. Subsequently by
      adding all the points together, a risk scoring model was established with a value
      higher than 45 as being at risk to develop pancreatic cancer. CONCLUSION:
      Smoking, drinking, high meat diet and diabetes are major risk factors for
      pancreatic cancer. A risk model for pancreatic cancer in Chinese Han population
      has been established with an 88.9% sensitivity and a 97.6% specificity.

PMID- 16610027
TI  - Prevalence of hepatitis B virus precore stop codon mutations in chronically
      infected children.
AB  - AIM: To find out whether there is a significant difference in the prevalence of
      the precore stop codon mutation between HBeAg positive and anti-HBe positive
      children. METHODS: We investigated a large pediatric population of 155 European
      children (mean age 10.9 years) with chronic hepatitis B by PCR and direct
      sequencing. Ninety were HBeAg positive and 65 had seroconversion to anti-HBe.
      Additionally genotyping was performed. RESULTS: Seventy-four (48%) of the
      sequenced HBV strains were attributed to genotype D and 81 (52%) to genotype A.
      In the group of 90 HBeAg positive patients, 2 (2.2%) 1896-G-to-A transitions
      leading to precore stop codon mutation were found, and in the group of 65 anti
      HBe positive children, 5 (7.7%) were identified harbouring HBeAg-minus mutants.
      The difference was not statistically significant (P = 0.13). CONCLUSIONS: HBeAg
      minus variants as predominant viral HB strains play a minor role in the course of
      chronic hepatitis B in European children.

PMID- 16610028
TI  - Copper toxicosis gene MURR1 is not changed in Wilson disease patients with normal
      blood ceruloplasmin levels.
AB  - AIM: To analyze our Wilson disease patient cohort (n=106) for alterations in the
      gene coding for MURR1. METHODS: Patients with an established diagnosis of Wilson
      disease but normal ceruloplasmin blood levels were chosen for our study (n = 14).
      Patients with two known disease-causing mutations in the ATP7B gene were not
      included. The three exons of the human MURR1 gene were sequenced after
      amplification of the genomic DNA by polymerase chain reaction. RESULTS: Our study
      did not reveal any mutations leading to an amino acid change in the MURR1
      sequence of Wilson disease patients. A polymorphism at 472 bp of the coding
      sequence could be confirmed. CONCLUSION: The MURR1 gene plays no role in the
      pathogenesis of Wilson disease patients with normal serum ceruloplasmin levels.

PMID- 16610029
TI  - Actigraphy: A new diagnostic tool for hepatic encephalopathy.
AB  - AIM: To assess the actigraphy, an ambulatory and continuous monitoring of wrist
      motor activity fitted to study sleep/wake patterns in hepatic encephalopathy
      (HE). METHODS: Twenty-five cirrhotic patients (17 M, 8 F, mean age 56+/-11 years,
      24/25 alcoholic, Child-Pugh A , B, C: 2, 6, 17) were included. The patients were
      classified into 3 groups: stage 0 group (n = 12), stage 1-2 group (n = 6), and
      stage 3-4 group (n = 7) of encephalopathy. Over three consecutive days, patients
      had clinical evaluation 3 times a day with psychometric test, venous ammoniemia,
      flash visually evoked potentials (VEP), electroencephalogram and continuous
      actigraphic monitoring for 3 d, providing 5 parameters: mesor, amplitude,
      acrophase, mean duration of activity (MDAI) and inactivity (MDII) intervals.
      RESULTS: Serum ammonia and VEP did not differ among the 3 groups.
      Electroencephalography mean dominant frequency (MDF) correlated significantly
      with clinical stages of HE (r = 0.65, P = 0.003). The best correlation with HE
      stage was provided by actigraphy especially with MDAI (r = 0.7, P < 10(-4)) and
      mesor (r = 0.65, P < 10(-4)). MDAI correlated significantly with MDF (r = 0.62,
      0.004) and was significantly shorter in case of HE compared to patients without
      HE (stage 0: 5.33+/-1.6 min; stage 1-2: 3.28+/-1.4 min; stage 3-4: 2.52+/-1.1
      min; P < 0.05). Using a threshold of MDAI of less than 4.9 min, sensitivity,
      specificity, positive predictive value, negative predictive value for HE
      diagnosis were 85%, 67%, 73% and 80%, respectively. CONCLUSION: Actigraphy may be
      an objective method to identify HE, especially for early HE detection. Motor
      activity at the wrist correlates well with clinical stages of HE. MDAI and mesor
      are the most relevant parameters.

PMID- 16610030
TI  - Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4
      induced chronic liver damage in rats.
AB  - AIM: To investigate the hepatoprotective effect of manual acupuncture at
      Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats
      were injected intraperitoneally with CCl4 (1 mL/kg) and treated with manual
      acupuncture using reinforcing manipulation techniques at left GB34 (Yanglingquan)
      3 times a week for 10 wk. A non-acupoint in left gluteal area was selected as a
      sham point. To estimate the hepatoprotective effect of manual acupuncture at
      GB34, measurement of liver index, biochemical assays including serum ALT, AST,
      ALP and total cholesterol, histological analysis and blood cell counts were
      conducted. RESULTS: Manual acupuncture at GB34 reduced the liver index, serum
      ALT, AST, ALP and total cholesterol levels as compared with the control group and
      the sham acupuncture group. It also increased and normalized the populations of
      WBC and lymphocytes. CONCLUSION: Manual acupuncture with reinforcing manipulation
      techniques at left GB34 reduces liver toxicity, protects liver function and liver
      tissue, and normalizes immune activity in CCl4-intoxicated rats.

PMID- 16610031
TI  - Aberrant expression of krUppel-like factor 6 protein in colorectal cancers.
AB  - AIM: To investigate whether krUppel-like factor 6 (KLF6) plays an important role
      in the development and/or progression of colorectal cancer. METHODS: A total of
      123 formalin-fixed and paraffin-embedded colorectal cancer specimens were
      analyzed by immunohistochemistry using tissue microarray for the expression of
      KLF6 protein. The specimens were collected over a 3-year period in the
      laboratories at our large teaching hospital in Seoul, Republic of Korea. The
      correlation of KLF6 expression with clinicopathologic parameters was analyzed by
      chi2 test and Bartholomew test. RESULTS: Normal colonic epithelium showed weak to
      moderate expression of KLF6, whereas reduced KLF 6 expression or loss of KLF6
      expression was seen in 45 (36.6%) of the 123 colorectal carcinoma specimens.
      Interestingly, aberrant expression of KLF6 was detected in 25 (43.1%) of 58 cases
      with metastasis to regional lymph node and in 31 (47.0%) of 66 tumors more than 5
      cm in size. Statistically, loss of KLF6 expression was significantly associated
      with tumor size (P < 0.05). However, there was no significant correlation between
      KLF6 expression and Dukes'stage (Bartholomew test, P > 0.05), tumor location and
      lymph node metastasis (chi2 test, P > 0.05). CONCLUSION: Loss of KLF6 expression
      may be a common and early event in colorectal carcinogenesis.

PMID- 16610032
TI  - Acute myopathy associated with liver cirrhosis.
AB  - AIM: Many cirrhotic patients have muscular symptoms and rhabdomyolysis. However,
      myopathy associated with liver cirrhosis has not been established as a disease
      entity. We evaluated the clinical significance of acute myopathy associated with
      liver cirrhosis. METHODS: We retrospectively reviewed the medical records of 5440
      cirrhotic patients who had been admitted to Gyeongsang National University
      Hospital from August 1997 to January 2003. Among these, 99 developed acute
      myopathies, and they were analyzed with respect to clinical and laboratory
      parameters, and outcomes. RESULTS: The Child-Pugh classification at the time of
      myopathy onset was A in 3(3.1%) cases, B in 33(33.3%), and C in 63 (63.6%).
      Infection was identified as the most predisposing factor to myopathy. Fifty
      percent of 18 idiopathic cases who were tested for influenza antibody were
      positive. Forty-two of the 99 cases were complicated by acute renal failure, and
      25 (59.5%) of these expired. Apart from 6 cases lost to follow-up, 64 of 93
      recovered, giving a mortality rate of 31.2%. Mortality was higher in Child-Pugh
      class C than in B or A. CONCLUSION: Acute myopathy can develop as a serious
      complication in liver cirrhosis. Its frequency, severity and mortality depend on
      underlying liver function, and are higher in decompensated liver cirrhosis.
      Influenza should be considered as an etiologic factor in idiopathic cases. It is
      proposed that acute myopathy associated with liver cirrhosis be called 'hepatic
      myopathy', and that careful monitoring for hepatic myopathy is necessary in the
      patients with advanced liver cirrhosis.

PMID- 16610033
TI  - Signal transduction of bombesin-induced circular smooth muscle cell contraction
      in cat esophagus.
AB  - AIM: To investigate the mechanism of bombesin-induced circular smooth muscle cell
      contraction in cat esophagus. METHODS: Specific G protein or phospholipase C
      involved in cat esophagus contraction was identified, muscle cells were
      permeabilized with saponin. After permeabilization of muscle cells, the Gi3
      antibody inhibited bombesin-induced smooth muscle cell contraction. RESULTS:
      Incubation of permeabilized circular muscle cells with PLC-beta3 antibody could
      inhibit bombesin-induced contraction. H-7, chelerythrine (PKC inhibitor) and
      genistein (protein tyrosine kinase inhibitor) inhibited bombesin-induced
      contraction, but DAG kinase inhibitor, R59949, could not inhibit it. To examine
      which mitogen-activated protein kinase (MAPK) was involved in bombesin-induced
      contraction, the specific MAPK inhibitors (MEK inhibitor, PD98059 and p38 MAPK
      inhibitor, SB202190) were used. Preincubation of PD98059 blocked the contraction
      induced by bombesin in a concentration-dependent manner. However, SB202190 had no
      effects on contraction. CONCLUSION: Bombesin-induced circular muscle cell
      contraction in cat esophagus is madiated via a PKC or a PTK-dependent pathway or
      p44/p42 MAPK pathway.

PMID- 16610034
TI  - Molecularly defined adult-type hypolactasia in school-aged children with a
      previous history of cow's milk allergy.
AB  - AIM: To assess the role of lactase non-persistence/persistence in school-aged
      children and their milk-related symptoms. METHODS: The genotypes for the C/T(
      13910) variant associated with lactase non-persistence/ persistence were
      determined using PCR-minisequencing in a group of 172 children with a mean age of
      8.6 years (SE = 0.02, 93 boys) participating in a follow-up study for cow's milk
      allergy. The parents were asked to assess their children's milk consumption and
      abdominal symptoms. RESULTS: The presence of allergy to cow's milk was not
      associated with the C/C(-13910) genotype related with a decline of lactase enzyme
      activity during childhood (lactase non-persistence). The frequency of the C/C(
      13910) genotype (16%) was similar to published figures for the prevalence of
      adult-type hypolactasia in Finland. The majority of the children (90%) in this
      series consumed milk but 26% of their families suspected that their children had
      milk-related symptoms. Forty-eight percent of the children with the C/C(-13910)
      genotype did not drink milk at all or consumed a low lactose containing diet
      prior to the genotyping (P < 0.004 when compared to the other genotypes).
      CONCLUSION: Analysis of the C/T(-13910) polymorphism is an easy and reliable
      method for excluding adult-type hypolactasia in children with milk-related
      symptoms. Genotyping for this variant can be used to advise diets for children
      with a previous history of cow's milk allergy.

PMID- 16610036
TI  - Ultrasonic characterization of porcine liver tissue at frequency between 25 to 55
      MHz.
AB  - AIM: To study the relation between acoustic parameters and histological structure
      of biological tissue and to provide the basis for high-resolution image of
      biological tissues and quantitative ultrasonic diagnosis of liver disease.
      METHODS: Ultrasonic imaging and tissue characterization of four normal porcine
      liver and five cirrhotic liver tissue samples were performed using a high
      frequency imaging system. RESULTS: The acoustic parameters of cirrhotic liver
      tissue were larger than those of normal liver tissue. The sound velocity was 1577
      m/s in normal liver tissue and 1631 m/s in cirrhotic liver tissue. At 35 MHz, the
      attenuation coefficient was 3.0 dB/mm in normal liver tissue and 4.1 dB/mm in
      cirrhotic liver tissue. The backscatter coefficient was 0.00431 dB/Srmm in
      cirrhotic liver tissue and 0.00303 dB/Srmm in normal liver tissue. The
      backscatter coefficient increased with the frequency. The high frequency images
      coincided with their histological features. CONCLUSION: The acoustic parameters,
      especially the sound backscatter coefficient, are sensitive to the changes of
      liver tissues and can be used to differentiate between the normal and
      pathological liver tissues. High frequency image system is a useful device for
      high-resolution image and tissue characterization.

PMID- 16610035
TI  - Gilbert's syndrome: High frequency of the (TA)7 TAA allele in India and its
      interaction with a novel CAT insertion in promoter of the gene for bilirubin UDP
      glucuronosyltransferase 1 gene.
AB  - AIM: To identify the variants in UDP-glucuronosyltransferase 1 (UGT1A1) gene in
      Gilbert's syndrome (GS) and to estimate the association between homozygosity for
      TA insertion and GS in India, as well as the frequency of TA insertion and its
      impact among normal controls in India. METHODS: Ninety-five GS cases and 95
      normal controls were selected. Liver function and other tests were done. The
      promoter and all 5 exons of UGT1A1 gene were resequenced. Functional assessment
      of a novel trinucleotide insertion was done by in silico analysis and by
      estimating UGT1A1 promoter activity carried out by luciferase reporter assay of
      appropriate constructs in Hep G2 cell line. RESULTS: Among the GS patients, 80%
      were homozygous for the TA insertion, which was several-fold higher than reports
      from other ethnic groups. The mean UCB level was elevated among individuals with
      only one copy of this insertion, which was not significantly different from those
      with two copies. Many new DNA variants in UGT1A1 gene were discovered, including
      a trinucleotide (CAT) insertion in the promoter found in a subset (10%) of GS
      patients, but not among normal controls. In-silico analysis showed marked changes
      in the DNA-folding of the promoter and functional analysis showed a 20-fold
      reduction in transcription efficiency of UGT1A1 gene resulting from this
      insertion, thereby significantly elevating the UCB level. CONCLUSION: The genetic
      epidemiology of GS is variable across ethnic groups and the epistatic
      interactions among UGT1A1 promoter variants modulate bilirubin glucuronidation.

PMID- 16610037
TI  - Antiviral effect of Chinese medicine jiaweisinisan in hepatitis B virus
      transgenic mice.
AB  - AIM: To study the antiviral effect of Chinese medicine jiaweisinisan (JWSNS) on
      hepatitis B virus (HBV) infection in transgenic mice (TGM). METHODS: Twenty two 6
      8 wk old HBV TGM in the third generation were divided into TGM control group and
      TGM treated group randomly. The normal control group included ten normal BC 57L/6
      mice at the same age. The mice in treated group were administrated with JWSNS at
      the concentration of 4 g/mL and the dosage of 50 g/kg per d for 30 d, while the
      mice in TGM control group and normal control group were administrated with normal
      saline at the same dosage and the same time. Polymerase chain reaction (PCR) was
      used to assess the contents of HBV DNA in serum of HBV TGM before and after
      treatments, whereas blot hybridization was utilized to measure the contents of
      HBV DNA in the liver of both HBV TGM and normal BC 57L/6 mice. RESULTS: The
      levels of serum HBV DNA in TGM treated group were remarkably decreased after the
      treatment of JWSNS (7.662+/-0.78 vs 5.22+/-3.14, P < 0.05), while there was no
      obvious change after administration of normal saline in TGM control group
      (7.125+/-4.26 vs 8.932+/-5.12, P > 0.05). The OD values of HBV DNA in the livers
      of the mice in TGM treated group were significantly lower than those of TGM
      control group (0.274+/-0.096 vs 0.432+/-0.119, P < 0.01). CONCLUSION: JWSNS
      exerts suppressive effects on HBV DNA in the serum and liver of TGM.

PMID- 16610038
TI  - Effect of explosive noise on gastrointestinal transit and plasma levels of
      polypeptide hormones.
AB  - AIM: To investigate the effect of firing noise on gastrointestinal transit and
      probe its mechanism by measuring the levels of plasma polypeptide hormones.
      METHODS: A total of 64 SD rats were randomly divided into a control group and
      three stimulating groups. Firing noise of different intensity by sub-machine guns
      was used as inflicting factor. The effect of firing noise on liquid substance
      gastrointestinal transit and solid substance gastrointestinal transit was
      observed by measuring the ratio of carbon powder suspension transmitting and
      barium sticks transmitting respectively. Plasma levels of polypeptide hormones
      were measured by radio-immunoassay. RESULTS: The noise accelerated
      gastrointestinal transit of solid food by more than 80 db;and accelerated
      gastrointestinal transit of liquid food significantly by more than 120 db.
      Meantime, plasma levels of plasma motilin (MTL)(157.47+/-16.08; 151.90+/-17.08),
      somatostatin (SS)(513.97+/-88.77; 458.25+/-104.30), substance P (SP)(115.52+/
      20.70; 110.28+/-19.96) and vasoactive intestinal peptide (VIP) (214.21+/-63.17;
      251.76+/-97.24) remarkably changed also. CONCLUSION: Within a certain intensity
      range, the firing noise changes the levels of rat plasma gastrointestinal
      hormones, but the gastrointestinal transit is still normal. Beyond the range, the
      noise induces plasma hormone levels disturbance and gastrointestinal transit
      disorder.

PMID- 16610039
TI  - Assay of gastrin and somatostatin in gastric antrum tissues of children with
      chronic gastritis and duodenal ulcer.
AB  - AIM: To study the expressions of gastrin (GAS) and somatostatin (SS) in gastric
      antrum tissues of children with chronic gastritis and duodenal ulcer and their
      role in pathogenic mechanism. METHODS: Specimens of gastric antrum mucosa from 83
      children were retrospectively analyzed. Expressions of GAS and SS in gastric
      antrum tissues were assayed by the immunohistochemical En Vision method. RESULTS:
      The expressions of GAS in chronic gastritis Hp+ group (group A), chronic
      gastritis Hp-group (group B), the duodenal ulcer Hp+group (group C), duodenal
      ulcer Hp-group (group D), and normal control group (group E) were 28.50+4.55,
      19.60+2.49, 22.69+2.71, 25.33+4.76, and 18.80+2.36, respectively. The value in
      groups A-D was higher than that in group E. The difference was not statistically
      significant. The expressions of SS in groups A-E were 15.47+1.44, 17.29+2.04,
      15.30+1.38, 13.11+0.93 and 12.14+1.68, respectively. The value in groups A-D was
      higher than that in group E. The difference was also not statistically
      significant. CONCLUSION: The expressions of GAS and SS are increased in children
      with chronic gastritis and duodenal ulcer.

PMID- 16610040
TI  - Cholelithiasis associated with haemolytic-uraemic syndrome.
AB  - Cholelithiasis occurs infrequently in the paediatric age group. Hereditary
      spherocytosis, sickle cell anaemia and thalassemia are the haemolytic disorders
      most commonly associated with development of gall stones in paediatric age group.
      The question is whether an isolated episode of haemolysis can cause gallstones.

PMID- 16610041
TI  - Extended surgical resection for xanthogranulomatous cholecystitis mimicking
      advanced gallbladder carcinoma: A case report and review of literature.
AB  - Xanthogranulomatous cholecystitis (XGC) is a destructive inflammatory disease of
      the gallbladder, rarely involving adjacent organs and mimicking an advanced
      gallbladder carcinoma. The diagnosis is usually possible only after pathological
      examination. A 46 year-old woman was referred to our center for suspected
      gallbladder cancer involving the liver hilum, right liver lobe, right colonic
      flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde
      cholangiography (ERC) showed high-grade dysplasia. The patient underwent an en
      bloc resection of the mass, consisting of right lobectomy, right hemicolectomy,
      and a partial duodenal resection. Pathological examination unexpectedly revealed
      an XGC. Only six cases of extended surgical resections for XGC with direct
      involvement of adjacent organs have been reported so far. In these cases, given
      the possible coexistence of XGC with carcinoma, malignancy cannot be excluded,
      even after cytology and intraoperative frozen section investigation. In
      conclusion, due to the poor prognosis of gallbladder carcinoma on one side and
      possible complications deriving from highly aggressive inflammatory invasion of
      surrounding organs on the other side, it seems these cases should be treated as
      malignant tumors until proven otherwise. Clinicians should include XGC among the
      possible differential diagnoses of masses in liver hilum.

PMID- 16610042
TI  - Development of multiple myeloma in a patient with chronic hepatitis C: A case
      report and review of the literature.
AB  - An association between chronic hepatitis C virus (HCV) infection and essential
      mixed cryoglobulinaemia and non-Hodgkin lymphoma (NHL) has been suggested.
      However, a causative role of HCV in these conditions has not been established.
      The authors report a case of a 50 year-old woman with chronic hepatitis C (CHC)
      who has been followed up since 1998 due to a high viral load, genotype 1b and
      moderately elevated liver function tests (LFTs). Laboratory data and liver biopsy
      revealed moderate activity (grade: 5/18, stage: 1/6). In April 1999, one-year
      interferon therapy was started. HCV-RNA became negative with normalization of
      LFTs. However, the patient relapsed during treatment. In September 2002, the
      patient was admitted for chronic back pain. A CT examination demonstrated
      degenerative changes. In March 2003, multiple myeloma was diagnosed (IgG-kappa,
      bone ma-rrow biopsy: 50% plasma cell infiltration). MRI revealed a compression
      fracture of the 5th lumbar vertebral body and an abdominal mass in the right
      lower quadrant, infiltrating the canalis spinalis. Treatment with vincristine,
      adriamycin and dexamethasone (VAD) was started and bisphosphonate was
      administered regularly. In January 2004, after six cycles of VAD therapy, the
      multiple myeloma regressed. Thalidomide, as a second line treatment of refractory
      multiple myeloma (MM) was initiated, and followed by peginterferon-alpha2b and
      ribavirin against the HCV infection in June. In June 2005, LFTs returned to
      normal, while HCV-RNA was negative, demonstrating an end of treatment response.
      Although a pathogenic role of HCV infection in malignant lymphoproliferative
      disorders has not been established, NHL and possibly MM may develop in CHC
      patients, supporting a role of a complex follow-up in these patients.

PMID- 16610043
TI  - A rare case of enteropathy-associated T-cell lymphoma presenting as acute renal
      failure.
AB  - Enteropathy-associated T-cell lymphoma (EATCL) is a high grade, pleomorphic
      peripheral T-cell lymphoma usually with cytotoxic phenotypes. We describe a first
      case of patient with EATCL that is remarkable for its fulminant course and
      invasion of both kidneys manifested as acute renal failure. The patient was a 23
      year old woman with a long history of celiac disease. She was presented with
      acute renal failure and enlarged mononuclear infiltrated kidneys. Diagnosis of
      tubulointerstitial nephritis and polyserositis was confirmed with consecutive
      pulse doses of steroid therapy. After recovery, she had disseminated disease two
      months later. Magnetic resonance imaging showed thickened intestine wall,
      extremely augmented kidneys, enlarged intra-abdominal lymph nodes with extra
      luminal compression of common bile duct. Laparotomy with mesenterial adipous
      tissue and lymph glands biopsy was done. Consecutive pathophysiological and
      immunohistochemical analyses confirmed the diagnosis of EATCL: CD45RO+, CD43+,
      CD3+. The revision of renal pathophysiology substantiated the diagnosis. The
      patient received chemotherapy, but unfortunately she died manifesting signs of
      pulmonary embolism caused by tumor cells.

PMID- 16610044
TI  - An interesting cause of esophageal ulcer etiology: Multiple myeloma of IgG kappa
      subtype.
AB  - Multiple myeloma is a neoplasm of mature and immature plasma cells. A 50-year-old
      woman with lumbago, dysphagia, and left arm pain was presented. Upper
      endoscopical examination was performed. There was an exudate-covered ulcer in the
      distal esophagus, located at 30-32 cm from the incisors, covering the whole
      mucosa. Histopathological examination of the specimens obtained from the lesion
      showed the involvement of plasma cells consistent with multiple myeloma of IgG
      kappa subtype. Esophageal involvement of multiple myeloma should be kept in mind
      in patients presenting with dysphagia.

PMID- 16610045
TI  - Co-localization hypothesis: a mechanism for the intrapancreatic activation of
      digestive enzymes during the early phases of acute pancreatitis.
AB  - Acute pancreatitis is generally believed to be a disease in which the pancreas is
      injured by digestive enzymes that it normally produces. Most of the potentially
      harmful digestive enzymes produced by pancreatic acinar cells are synthesized and
      secreted as inactive zymogens which are normally activated only upon entry into
      the duodenum but, during the early stages of acute pancreatitis, those zymogens
      become prematurely activated within the pancreas and, presumably, that activation
      occurs within pancreatic acinar cells. The mechanisms responsible for
      intracellular activation of digestive enzyme zymogens have not been elucidated
      with certainty but, according to one widely recognized theory (the "co
      localization hypothesis"), digestive enzyme zymogens are activated by lysosomal
      hydrolases when the two types of enzymes become co-localized within the same
      intracellular compartment. This review focuses on the evidence supporting the
      validity of the co-localization hypothesis as an explanation for digestive enzyme
      activation during the early stages of pancreatitis. The findings, summarized in
      this review, support the conclusion that co-localization of lysosomal hydrolases
      with digestive enzyme zymogens plays a critical role in permitting the
      intracellular activation of digestive enzymes that leads to acinar cell injury
      and pancreatitis.

PMID- 16610046
TI  - Novel susceptibility genes in inflammatory bowel disease.
AB  - The inflammatory bowel disease, Crohn's disease and ulcerative colitis, are
      polygenic disorders with important environmental interactions. To date, the most
      widely adopted approach to identifying susceptibility genes in complex diseases
      has involved genome wide linkage studies followed by studies of positional
      candidate genes in loci of interest. This review encompasses data from studies
      into novel candidate genes implicated in the pathogenesis of inflammatory bowel
      disease. Novel techniques to identify candidate genes-genome wide association
      studies, yeast-two hybrid screening, microarray gene expression studies and
      proteomic profiling, are also reviewed and their potential role in unravelling
      the pathogenesis of inflammatory bowel disease are discussed.

PMID- 16610047
TI  - Chemotherapy as a component of multimodal therapy for gastric carcinoma.
AB  - Prognosis of locally advanced gastric cancer remains poor, and several
      multimodality strategies involving surgery, chemotherapy, and radiation have been
      tested in clinical trials. Phase III trial testing the benefit of postoperative
      adjuvant chemotherapy over treatment with surgery alone have revealed little
      impact on survival, with the exception of some small trials in Western nations. A
      large trial from the United States exploring postoperative chemoradiation was the
      first major success in this category. Results from Japanese trials suggest that
      moderate chemotherapy with oral fluoropyrimidines may be effective against less
      advanced (T2-stage) cancer, although another confirmative trial is needed to
      prove this point. Investigators have recently turned to neoadjuvant chemotherapy,
      and some promising results have been reported from phase II trials using active
      drug combinations. In 2005, a large phase III trial testing pre- and
      postoperative chemotherapy has proven its survival benefit for resectable gastric
      cancer. Since the rate of pathologic complete response is considered to affect
      treatment results of this strategy, neoadjuvant chemoradiation that further
      increases the incidence of pathologic complete response could be a breakthrough,
      and phase III studies testing this strategy may be warranted in the near future.

PMID- 16610048
TI  - Expression of midkine and its clinical significance in esophageal squamous cell
      carcinoma.
AB  - AIM: To investigate the expression of midkine in esophageal squamous cell
      carcinoma (ESCC) and analyze its relationship with clinicopathological features.
      METHODS: RT-PCR and immunocytochemical staining were used to detect the
      expression of midkine mRNA and protein in EC109 cells, respectively. Then the
      expression of midkine in 66 cases of ESCC samples were detected by
      immunohistochemistry using monoclonal antibodies against human midkine. RESULTS:
      Midkine was expressed in EC109 cell by RT-PCR and immunocytochemistry. The
      immunoreactivity was detected in 56.1% (37/66) of the ESCC samples. The
      expression of midkine was found in cytoplasm of tumor cells. Notably, the
      intensity of midkine was stronger at the area abundant in vessels and the
      invading border of the tumors. Midkine was more intensely expressed in well
      differentiated tumors (76.9%) than in moderately and poorly differentiated tumors
      (43.1% and 41.2%, respectively) (P<0.05). There was no statistically significant
      correlation between midkine expression and gender, age, clinical stage, lymph
      node metastasis or survival in ESCC. CONCLUSION: Midkine is overexpressed in
      ESCC. It may play a role in tumor angiogenesis and invasion. The expression of
      midkine is correlated with tumor cell differentiation in ESCC. The more poorly
      tumor cells differentiate, the weaker midkine expresses.

PMID- 16610049
TI  - Relationship between somatostatin receptor subtype expression and
      clinicopathology, Ki-67, Bcl-2 and p53 in colorectal cancer.
AB  - AIM: To study the SSTR1, 2, 3, 4, 5 expression and their relationships with
      clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in
      colorectal cancer cells. METHODS: Immunohistochemical staining of five SSTR
      subtypes, Ki-67, Bcl-2 and p53 was performed by the standard streptavidin
      peroxidase (SP) technique for the paraffin sections of 127 colorectal cancers.
      and expression of five SSTR subtypes in 40 specimens of normal colorectal mucosae
      was detected with the same method. RESULTS: Positive staining for five SSTR
      subtypes was observed in colorectal cancer cells and normal colorectal mucosae.
      SSTR1 was the most predominant subtype in both colorectal cancer and normal
      colorectal mucosa, and the second was SSTR5 or SSTR2. As compared with normal
      colorectal mucosa, SSTR4 was more frequently expressed in colorectal cancer cells
      (2.5% vs 18.9%, P<0.05); the expression of SSTR2, 4, 5 in moderately to well
      differentiated colorectal adenocarcinoma was significantly higher than that in
      poorly differentiated ones (P<0.05), the SSTR1 expression in colorectal cancer
      with positive lymph node metastasis was significantly higher than that with
      negative lymph node metastasis (72.2% and 54.5%,P<0.05). In addition, in the
      ulcerative type of colorectal cancer, SSTR2 expression was obviously decreased
      (P<0.05); the correlation did not reach a statistical significance between the
      five SSTR subtypes expression and Dukes'stages (P>0.05), but the frequency of
      SSTR1 expression increased with Dukes'stage, while SSTR3 and SSTR5 expression
      decreased with Dukes' stage. Moreover, there was no correlation between
      expression of the five SSTR subtypes and other clinicopathological factors such
      as age, sex, tumor site, tumor depth, distant metastasis. The proliferative
      indexes in colorectal cancer cells with negative expression of SSTR2 and SSTR3
      were significantly higher than that with positive expression (P<0.05). The Bcl-2
      expression in colorectal cancer cells with positive expression of SSTR1, 2, 3, 5
      was significantly lower than that with negative expression (P<0.05). There was no
      correlation between five SSTR subtypes and p53 expression. CONCLUSION: The most
      predominant SSTR subtype is SSTR1, and the second is SSTR2 or SSTR5. Five SSTR
      subtypes play different roles in the development of colorectal cancer. SSTR2 and
      SSTR3 can inhibit the proliferation and promote apoptosis of tumor cells.

PMID- 16610050
TI  - Adeno-associated virus-mediated heme oxygenase-1 gene transfer suppresses the
      progression of micronodular cirrhosis in rats.
AB  - AIM: To test the hypothesis that enhancement of the activity of heme oxygenase
      can interfere with processes of fibrogenesis associated with recurrent liver
      injury, we investigated the therapeutic potential of over-expression of heme
      oxygense-1 in a CCl(4)-induced micronodular cirrhosis model. METHODS: Recombinant
      adeno-associated viruses carrying rat HO-1 or GFP gene were generated. 1x 10(12)
      vg of adeno-associated viruses were administered through portal injection at the
      time of the induction of liver fibrosis. RESULTS: Conditioning the rat liver with
      over-expression of HO-1 by rAAV/HO-1 significantly increased the HO enzymatic
      activities in a stable manner. The development of micronodular cirrhosis was
      significantly inhibited in rAAV/HO-1-transduced animals as compared to controls.
      Portal hypertension was markedly diminished in rAAV/HO-1-transduced animals as
      compared to controls, whereas there are no significant changes in systolic blood
      pressure. This finding was accompanied with improved liver biochemistry, less
      infiltrating macrophages and less activated hepatic stellate cells (HSCs) in
      rAAV/HO-1-transduced livers. CONCLUSION: Enhancement of HO activity in the livers
      suppresses the development of cirrhosis.

PMID- 16610051
TI  - Rosuvastatin reduces rat intestinal ischemia-reperfusion injury associated with
      the preservation of endothelial nitric oxide synthase protein.
AB  - AIM: To investigate the protective effect of rosuvastatin on ischemia-reperfusion
      (I-R)-induced small intestinal injury and inflammation in rats, and to determine
      the effect of this agent on the expression of endothelial nitric oxide synthase
      (eNOS) protein. METHODS: Intestinal damage was induced in male Sprague-Dawley
      rats by clamping both the superior mesenteric artery and the celiac trunk for 30
      min, followed by reperfusion for 60 min. Rosuvastatin dissolved in physiological
      saline was administered intraperitoneally 60 min before ischemia. The severity of
      the intestinal mucosal injury and inflammation were evaluated by several
      biochemical markers, as well as by histological findings. The protein levels of
      eNOS were determined by Western blot. RESULTS: The levels of both intraluminal
      hemoglobin and protein, as indices of mucosal damage, were significantly
      increased in the I-R group compared with those in the sham-operated group. These
      increases, however, were significantly inhibited by treatment with rosuvastatin
      in a dose-dependent manner. The protective effects of rosuvastatin were also
      confirmed by histological findings. Exposure of the small intestine to I-R
      resulted in mucosal inflammation characterized by significant increases in
      thiobarbituric acid-reactive substances, tissue-associated myeloperoxidase
      activity, and the mucosal contents of rat cytokine-induced neutrophil
      chemoattractant-1 (CINC-1) and tumor necrosis factor-alpha (TNF-alpha). These
      increases in inflammatory parameters after I-R were significantly inhibited by
      pretreatment with rosuvastatin at a dose of 10 mg/kg. Furthermore, mRNA
      expression of CINC-1 and TNF-alpha was increased after I-R, and this increase was
      also inhibited by rosuvastatin. The mucosal protein levels of eNOS decreased
      during I-R, but were preserved in rats treated with rosuvastatin. CONCLUSION:
      Rosuvastatin inhibits rat intestinal injury and inflammation induced by I-R, and
      its protection is associated with the preservation of eNOS protein.

PMID- 16610052
TI  - Usefulness of biopsying the major duodenal papilla to diagnose autoimmune
      pancreatitis: a prospective study using IgG4-immunostaining.
AB  - AIM: To examine the histological and immunohistochemical findings of biopsy
      specimens taken from the major duodenal papilla of autoimmune pancreatitis (AIP)
      patients. METHODS: The major duodenal papilla in the resected pancreas of 3
      patients with AIP and of 5 control patients [pancreatic carcinoma (n = 3) and
      chronic alcoholic pancreatitis (n = 2)] was immunostained using anti-CD4-T cell,
      CD8-T cell and IgG4 antibodies. Forceps biopsy specimens taken from the major
      duodenal papilla of 2 patients with AIP and 5 control patients with suspected
      papillitis were prospectively taken during duodenoscopy and immunohistochemically
      examined. RESULTS: Moderate or severe lymphoplasmacytic infiltration including
      many CD4-positive or CD8-positive T lymphocytes and IgG4-positive plasma cells
      (>or=10/HPF), was observed in the major duodenal papilla of all 3 patients with
      AIP. The same findings were also detected in the biopsy specimens taken from the
      major duodenal papilla of 2 patients with AIP, but in controls, there were only a
      few (<or=3/HPF) IgG4-positive plasma cells infiltrating the major duodenal
      papilla. CONCLUSIONS: An abundant infiltration of IgG4-positive plasma cells is
      specifically detected in the major duodenal papilla of patients with AIP.
      Although this is a preliminary study, IgG4-immunostaining of biopsy specimens
      taken from the major duodenal papilla may support the diagnosis of AIP.

PMID- 16610053
TI  - Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine
      levels and gastric ulcer healing in rats.
AB  - AIM: To compare the effects of Aloe vera and sucralfate on gastric
      microcirculatory changes, cytokine levels and gastric ulcer healing. METHODS:
      Male Spraque-Dawley rats (n=48) were divided into four groups. Group1 served as
      control group, group 2 as gastric ulcer group without treatment, groups 3 and 4
      as gastric ulcer treatment groups with sucralfate and Aloe vera. The rats from
      each group were divided into 2 subgroups for study of leukocyte adherence, TNF
      alpha and IL-10 levels and gastric ulcer healing on days 1 and 8 after induction
      of gastric ulcer by 20% acetic acid. RESULTS: On day 1 after induction of gastric
      ulcer, the leukocyte adherence in postcapillary venule was significantly (P<0.05)
      increased in the ulcer groups when compared to the control group. The level of
      TNF-alpha was elevated and the level of IL-10 was reduced. In the ulcer groups
      treated with sucralfate and Aloe vera, leukocyte adherence was reduced in
      postcapillary venule. The level of IL-10 was elevated, but the level of TNF-alpha
      had no significant difference. On day 8, the leukocyte adherence in postcapillary
      venule and the level of TNF-alpha were still increased and the level of IL-10 was
      reduced in the ulcer group without treatment. The ulcer treated with sucralfate
      and Aloe vera had lower leukocyte adherence in postcapillary venule and TNF-alpha
      level. The level of IL-10 was still elevated compared to the ulcer group without
      treatment. Furthermore, histopathological examination of stomach on days 1 and 8
      after induction of gastric ulcer showed that gastric tissue was damaged with
      inflammation. In the ulcer groups treated with sucralfate and Aloe vera on days 1
      and 8, gastric inflammation was reduced, epithelial cell proliferation was
      enhanced and gastric glands became elongated. The ulcer sizes were also reduced
      compared to the ulcer group without treatment. CONCLUSION: Administration of 20%
      acetic acid can induce gastric inflammation, increase leukocyte adherence in
      postcapillary venule and TNF-alpha level and reduce IL-10 level. Aloe vera
      treatment can reduce leukocyte adherence and TNF-alpha level, elevate IL-10 level
      and promote gastric ulcer healing.

PMID- 16610054
TI  - Construction and evaluation of anti-gastrin immunogen based on P64K protein.
AB  - AIM: To construct two kinds of anti-gastrin immunogen based on P64K protein from
      Neisseria meningitids and to compare their immunogenic effect. METHODS: G17P64K
      gene was cloned and ligated into pET28a plasmid, then transformed into BL21(DE3).
      After inoculation of LB medium and IPTG induction, the recombinant protein was
      solubly expressed at a high level. The purification of G17P64K fusion protein was
      similar to that of P64K. An initial step of purification consisting of 30%
      saturated ammonium sulfate precipitation was done. Additional fine optimizations
      included phenyl-sepharose, G200 Sephadex gel filtration and Q-sepharose anion
      exchanger chromatography. Highly purified protein was obtained and sequenced at
      the N-terminal amino acid residues. Polypeptide was synthesized by Fmoc solid
      phase chemical method and cross-linked to carrier protein P64K and DT mutant by
      MBS method and then the rabbit anti-gastrin 17 antibody was prepared by
      immunizing rabbit with cross-linked and fused protein. The titer and the activity
      in vitro of antibody were assessed. RESULTS: G17P64K gene and the recombinant
      bacteria were obtained. After four steps purification, protein sample that has
      the purity above 90% was achieved. At the 84(th) day after the first
      immunization, the titer of antibody against cross-linked protein reached 51,200.
      Evaluation of the antibody in vitro manifested that it had a high inhibitory
      activity on the growth of tumor cell SW480. CONCLUSION: The P64K-polypeptide
      cross-linked immunogen immunized rabbit and achieved a higher titer antibody
      against gastrin 17 than the G17P64K fusion protein immunogen, which could inhibit
      the growth of the tumor cell SW480.

PMID- 16610055
TI  - Effect of Chinese medicine Qinggan Huoxuefang on inducing HSC apoptosis in
      alcoholic liver fibrosis rats.
AB  - AIM: To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of
      liver function and pathology in rats, and to analyze the mechanism. METHODS:
      Wistar rats were divided into three groups at random: normal control group
      (12),micro-amount carbon tetrachloride group (CCl(4))(12) and model group A (60).
      The model group A was ingested with the mixture (500 mL/L alcohol, 8 mL/kg per
      day; corn oil, 2 mL/kg per day; pyrazole, 24 mg/kg per day) once a day and
      intraperitoneal injections of 0.25 mL/kg of a 250 mL/L solution of CCl(4) in
      olive oil twice a week for 12 wk. The CCl(4) group received intraperitoneal
      injections only. At the end of 8 wk the model group A (60) was divided into 5
      subgroups: model group, Xiaochaihu Chongji (XCH) group, QGHXF high dose group,
      moderate dose group and low dose group, and were given the drugs respectively. At
      the end of 12 wk, all the rats were killed and blood samples collected, as well
      as liver tissue. Blood samples were used for evaluation of alanine transaminase
      (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma
      glutamyltransferase (gamma-GT). Liver specimens were obtained for routine HE,
      apoptosis gene array and flow cytometry analysis. RESULTS: A liver fibrosis
      animal model was successfully established. Fibrosis was obviously reduced in
      QGHXF high dose group, and no fibrosis formed in CCl(4) group. Compared with
      model group the QGHXF group and XCH group could obviously decrease the level of
      ALT, AST, ALP, and GGT (P<0.05). QGHXF high dose group was better than XCH group
      in ALT (615+/-190 vs 867+/-115), and AST(1,972+/-366 vs 2,777+/-608). Moreover,
      QGHXF could reduce liver inflammation, fibrosis-induced hepatic stellate cell
      (HSC) apoptosis and regulate apoptosis gene expression. The HSC apoptosis rates
      of QGHXF groups were 22.4+/-3.13, 13.79+/-2.26 and 10.07+/-1.14, higher than
      model group, 6.58+/-1.04 (P<0.05). Compared to model group, 39 genes were up
      regulated, 11 solely expressed and 17 down-regulated in high dose group.
      CONCLUSION: QGHXF can improve liver fibrosis and induce HSC apoptosis.

PMID- 16610056
TI  - Changes in growth factor and cytokine expression in biliary obstructed rat liver
      and their relationship with delayed liver regeneration after partial hepatectomy.
AB  - AIM: To study the effects of obstructive jaundice on liver regeneration after
      partial hepatectomy. METHODS: Hepatocyte growth factor (HGF), its receptor, c
      Met, vascular endothelial growth factor (VEGF) and transforming growth factor
      beta1 (TGF-beta1) mRNA expression in both liver tissue and isolated liver cells
      were investigated after biliary obstruction (BO) by quantitative reverse
      transcription polymerase chain reaction (RT-PCR) using a LightCycler.
      Immunohistochemical staining for desmin and alpha-smooth muscle actin (alpha-SMA)
      was also studied. Regenerating liver weight and proliferating cell nuclear
      antigen (PCNA) labeling index, and growth factor expression were then evaluated
      after 70% hepatectomy with concomitant internal biliary drainage in BO rats or
      sham-operated rats. RESULTS: Hepatic TGF-beta1 mRNA levels increased
      significantly 14 days after BO, and further increased with duration of
      cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant.
      In cell isolates, TGF-beta1 mRNA was found mainly in the hepatic stellate cell
      (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs
      (desmin-positive cells) and activated HSCs (alpha-SMA-positive cells) in portal
      areas after BO. In a hepatectomy model, liver regeneration was delayed in BO
      rats, as compared to sham-operated rats. TGF-beta1 mRNA was significantly up
      regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in
      BO rats. CONCLUSION: BO induces HSCs proliferation and activation, leading to up
      regulation of TGF-beta1 mRNA and suppression of HGF mRNA in livers. These altered
      expression patterns may be strongly involved in delayed liver regeneration after
      hepatectomy with obstructive jaundice.

PMID- 16610057
TI  - Advanced gastrointestinal stromal tumor patients with complete response after
      treatment with imatinib mesylate.
AB  - AIM: Most gastrointestinal stromal tumors (GISTs) express constitutively
      activated mutant isoforms of kit kinase or platelet-derived growth factor
      receptor alpha (PDGFRA), which are potential therapeutic targets for imatinib
      mesylate (Glivec). Partial response occurred in almost two thirds of GIST
      patients treated with Glivec. However, complete response (CR) after Glivec
      therapy was sporadically reported. Here we illustrated advanced GIST patients
      with CR after Glivec treatment. METHODS: Between January 2001 and June 2005, 42
      advanced GIST patients were treated with Glivec. Patients were administered 400
      mg of Glivec in 100-mg capsules, taken orally daily with food. The response of
      the tumor to Glivec was evaluated after one month, three months, and every three
      months thereafter or whenever medical need was indicated. Each tumor of patients
      was investigated for mutations of kit or PDGFRA. RESULTS: The median follow-up
      time of the 42 advanced GIST patients treated with Glivec was 16.9 months (range,
      1.0-47.0 months). Overall, 3 patients had complete response CR (7.1%), 26 partial
      response (67.8%), 5 stationary disease (11.9%), and 3 progressive disease
      (11.9%). The median duration of Glivec administration for the three patients was
      36 months (range, 23-36 months). The median time to CR after Glivec treatment was
      20 months (range, 9-26 months). Deletion and insertion mutations of c-kit exon 11
      and insertion mutation of c-kit exon 9 were found in two cases and one case,
      respectively. CONCLUSION: Complete response (CR) can be achi-eved in selected
      advanced GIST patients treated with Glivec. The median time to CR after Glivec
      treatment was 20 months. Deletion and insertion mutations of kit exon 11 and
      insertion mutation of kit exon 9 contribute to the genetic features in these
      selected cases.

PMID- 16610058
TI  - Oxidative damage, pro-inflammatory cytokines, TGF-alpha and c-myc in chronic HCV
      related hepatitis and cirrhosis.
AB  - AIM: To assess whether a correlation exists between oxidative DNA damage
      occurring in chronic HCV-related hepatitis and expression levels of pro
      inflammatory cytokines, TGF-alpha and c-myc. METHODS: The series included 37
      patients with chronic active HCV-related hepatitis and 11 with HCV-related
      compensated cirrhosis. Eight-hydroxydeoxyguanosine in liver biopsies was
      quantified using an electrochemical detector. The mRNA expression of TNF-alpha,
      IL-1beta, TGF-alpha and c-myc in liver specimens was detected by semi
      quantitative comparative RT-PCR. RESULTS: TNF-alpha levels were significantly
      higher in hepatitis patients than in cirrhosis patients (P=0.05). IL-1beta was
      higher in cirrhosis patients (P=0.05). A significant correlation was found
      between TNF-alpha and staging (P=0.05) and between IL-1beta levels and grading
      (P=0.04). c-myc showed a significantly higher expression in cirrhosis patients
      (P=0.001). Eight-hydroxydeoxyguanosine levels were significantly higher in
      cirrhosis patients (P=0.05) and in HCV genotype 1 (P=0.03). Considering all
      patients, 8-hydroxydeoxyguanosine levels were found to be correlated with
      genotype (P=0.04) and grading (P=0.007). Also multiple logistic regression
      analysis demonstrated a significant correlation among the number of DNA adducts,
      TNF-alpha expression and HCV genotype (P=0.02). CONCLUSION: In chronic HCV
      related liver damage, oxidative DNA damage correlates with HCV genotype, grading
      and TNF-alpha levels. As HCV-related liver damage progresses, TNF-alpha levels
      drop while IL-1beta and c-myc levels increase, which may be relevant to liver
      carcinogenesis.

PMID- 16610059
TI  - Prevention of de novo HBV infection by the presence of anti-HBs in transplanted
      patients receiving core antibody-positive livers.
AB  - AIM: To analyze whether the presence of anti-HBs in liver transplant recipients
      is effective in preventing HBV infection. METHODS: Twenty-three patients
      receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc
      positive as a result of previous HBV infection. Of them, one also received HBV
      vaccine during the pre-liver transplantation period. Fourteen recipients were
      anti-HBs positive due to HBV vaccine administered during the pre-transplant
      period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive
      recipients and in 4/9 anti-HBc positive recipients. RESULTS: After a mean follow
      up period of 46 months, 1 recipient with protective serum anti-HBs levels
      developed de novo HBV infection as a consequence of immune escape HBV mutants.
      Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10
      patients with available liver biopsy (10%) had liver HBV-DNA at 13 mo post-liver
      transplantation without serum viral markers and did not develop de novo HBV
      infection. The vaccinated anti-HBc positive recipient without HBV vaccine
      response was HBV-DNA positive in serum and liver, viral DNA was continuously
      negative in the following tests, so a spontaneous seroconversion was diagnosed.
      CONCLUSION: The presence of anti-HBs as a result of HBV vaccine or past HBV
      infection seems to be effective at protecting patients receiving livers from anti
      HBc positive donors. However, the emergence of immune escape HBV mutants, which
      can evade the anti-HBs protection, should be considered as a risk of HBV
      infection.

PMID- 16610060
TI  - Prognosis following transcatheter arterial embolization for 121 patients with
      unresectable hepatocellular carcinoma with or without a history of treatment.
AB  - AIM: To retrospectively evaluate the prognosis of patients with hepatocellular
      carcinoma (HCC) with or without a history of therapy for HCC following
      transcatheter arterial embolization (TAE). METHODS: One hundred and twenty-one
      patients with HCC treated with TAE from 1992 to 2004 in our hospital were
      enrolled in this study. Eighty-four patients had a history of treatment for HCC,
      while 37 did not. At the time of entry, patients with extra-hepatic metastasis,
      portal vein tumor thrombosis, or Child-Pugh class C were excluded. TAE was
      repeated when recurrence of HCC was diagnosed by elevated tumor markers, or
      ultrasonography or dynamic computed tomography findings. RESULTS: Tumor size was
      larger and the number of tumors was fewer in patients without past treatment
      (P<0.01). However, there were no differences in tumor node metastasis (TNM) stage
      or survival rate between the 2 groups. A bilobular tumor and high level of alpha
      fetoprotein (AFP) (>100 ng/mL) were factors related to a poor prognosis in
      patients with a history of HCC. CONCLUSION: The prognosis following TAE is
      similar between HCC patients with and without past treatment. Early diagnosis of
      HCC or recurrent HCC and obtaining good local control against HCC before entry to
      a repeated TAE course can improve prognosis.

PMID- 16610061
TI  - Cryptogenic cirrhosis in the region where obesity is not prevalent.
AB  - AIM: Recent studies have demonstrated that obesity is the common feature of
      cryptogenic cirrhosis (CC) and non-alcoholic steatohepatitis. However, there is
      little information on CC in the region where obesity is not prevalent. METHODS:
      The clinical features, and the liver-related morbidity and mortality of CC were
      analyzed in Japan where the prevalence of obesity is low. Among 652 cirrhotic
      patients, we identified 29 patients (4.4%) with CC. Of these, 24 CC patients who
      were followed up for more than 6 months were compared in a case-control study
      with age-, sex-, and Child-Pugh score-matched controls having cirrhosis of viral
      etiology. RESULTS: Obesity (BMI>or=25 kg/m(2)), diabetes mellitus, and
      hypertriglyceridemia were more frequent, and the visceral fat area was larger in
      the CC patients than in the controls. The indices of insulin resistance were
      higher and the serum aminotransferase levels were lower in the CC patients than
      in the controls. Logistic regression analysis identified the elevated hemoglobin
      A1c, BMI>or=25 kg/m(2), and normal aminotransferase levels as independent
      predictors of CC. Kaplan-Meier analysis demonstrated lower occurrence of
      hepatocellular carcinoma and higher survival rate in the CC than in the controls
      in contrast to the similar cumulative probability of liver-related morbidity
      between those groups. CONCLUSION: CC more frequently presents with the clinical
      features suggestive of non-alcoholic steatohepatitis compared with controls even
      in the region where obesity is not prevalent. The lower occurrence of
      hepatocellular carcinoma and higher survival rate may indicate an indolent
      clinical course in CC as compared with viral cirrhosis.

PMID- 16610062
TI  - Safety advantage of endocut mode over endoscopic sphincterotomy for
      choledocholithiasis.
AB  - AIM: To evaluate whether an automatically controlled cut system (endocut mode)
      could reduce the complication rate of endoscopic sphincterotomy (EST) and serum
      hyperamylasemia after EST compared to the conventional blended cut mode. METHODS:
      From January 2001 to October 2003, 134 patients with choledocholithiasis were
      assigned to either endocut mode group or conventional blended cut mode group at
      the time of sphincterotomy. The two groups were retrospectively compared for the
      complications after EST and serum amylase level before and 24 h after the
      procedure. RESULTS: Of the 134 patients treated, 79 were assigned to conventional
      blended cut mode group and 55 to endocut mode group. There was no significant
      difference in age, sex, and serum amylase level before EST between the two
      groups. Complications were found in 5 patients of the endocut mode group (9%):
      hyperamylasemia (5 times higher than normal) in 4 and moderate pancreatitis in 1.
      Complications were found in 13 patients of the conventional blended cut mode
      group (16%): hyperamylasemia in 12 and moderate pancreatitis in 1. Serum amylase
      levels were elevated in both groups 24 h after EST (P<0.02). The average serum
      amylase level 24 h after EST in the conventional blended cut mode group was
      significantly higher than that in the endocut mode group (P<0.05). CONCLUSION:
      Endocut mode offers a safety advantage over conventional blended cut mode for
      pancreatitis after EST by reducing hyperamylasemia.

PMID- 16610063
TI  - Reduction of virus burden-induced splenectomy in patients with liver cirrhosis
      related to hepatitis C virus infection.
AB  - AIM: To examine the hepatitis C virus (HCV) levels and immunological markers in
      cirrhotic patients after splenectomy. METHODS: HCV RNA titers as well as cellular
      and humoral immune markers were determined in 20 cirrhotic patients after
      splenectomy and in 32 cirrhotic controls with an intact spleen. RESULTS: Serum
      HCV RNA titers were lower in the splenectomized patients than in the controls
      (186+/-225 x 10(3)copies/mL vs 541+/-417 x 10(3) copies/mL, P<0.01). HCV RNA was
      judged to have been spontaneously eradicated in 4 splenectomized patients, but in
      none of the controls. Natural killer cell activity was higher in the
      splenectomized patients than in the controls (41.2+/-19.3% vs 24.7+/-15.3%,
      P<0.01), and natural killer cell activity was negatively correlated to HCV RNA
      titers in the splenectomized patients except in those with serotype 2-related
      infection. The CD4/CD8 ratio was significantly lower in the splenectomized
      patients than in the controls. CONCLUSION: The findings suggest that splenectomy
      may diminish virus burden in cirrhotic patients with HCV infection at least in
      part, through augmentation of natural killer cell activity.

PMID- 16610065
TI  - Endoprosthesis implantation at the pharyngo-esophageal level: problems,
      limitations and challenges.
AB  - AIM: To present our experience with endoscopic placement of an esophageal
      endoprosthesis in 19 patients. METHODS: A retrospective evaluation was made for
      the use of 19 stents positioned at the level of the cervical esophagus: 11 for
      malignant tumours (7 causing obstruction, 4 complicated by an esophago -tracheal
      or -cutaneous fistula), and 8 for an acquired benign tracheo-esophageal fistula
      due to prolonged intubation. The covered Ultraflex stent was used in all cases
      except two. These two patients had an esophagocutaneous fistula following
      laryngectomy and a Flamingo Wall stent was used. RESULTS: Stent implantation was
      technically successful in all patients. Dysphagia score was improved from 3 to 2
      in stenosis patients, while sealing of the fistula was achieved in all cases. The
      median hospital stay was 3 d for malignant tumour patients and 13.5 d for
      esophagocutaneous fistula patients. One Ultraflex stent and two Flamingo Wall
      stents were easily removed 33 d and 3 months respectively after implantation when
      the fistulas had totally occluded. CONCLUSION: Endoprosthesis implantation for
      malignancy and/or fistula of malignant or benign origin at the level of the
      cervical esophagus is an easy, well tolerated, safe and effective procedure with
      no complications or mortality.

PMID- 16610064
TI  - Local regulator adrenomedullin contributes to the circulatory disturbance in
      cirrhotic rats.
AB  - AIM: To investigate whether adrenomedullin, a potent vasodilator peptide, plays a
      role in the circulatory disturbance in cirrhosis. METHODS: Cirrhosis was induced
      in rats by weekly gavage of carbon tetrachloride. Hemodynamic studies were
      performed in vivo using radioactive microspheres and in vitro using isolated
      aortic rings. The adrenomedullin concentrations were measured by
      radioimmunoassay. RESULTS: Acute administration of adrenomedullin to the control
      rats reduced the systemic arterial pressure along with an increase of serum
      levels of the stable metabolite of nitric oxide (NOx), in a dose-dependent
      manner. Chronic infusion of adrenomedullin reduced the vascular resistance and
      increased the blood flow in the systemic and splanchnic circulation. Intravenous
      administration of anti-adrenomedullin antibody did not affect any hemodynamic
      parameters in the cirrhotic rats, whereas this antibody ameliorated the blunted
      contractile response to phenylephrine, alpha-adrenergic receptor agonist, in the
      aortic rings of the cirrhotic rats. The adrenomedullin concentrations in the
      aorta were higher in the cirrhotic rats than in the controls, and correlated with
      the mean arterial pressure in the cirrhotic rats. Moreover, adrenomedullin
      blunted the contractile response to phenylephrine in both of the control aorta
      and cirrhotic aorta, but not in the presence of NG-nitro-L-arginine methyl ester,
      an NO synthase inhibitor. CONCLUSION: Adrenomedullin overproduced in the vascular
      wall may contribute to the circulatory disturbance in cirrhosis as a local
      regulator of the vascular tonus rather than a circulating hormone.

PMID- 16610066
TI  - Circadian variation in expression of G1 phase cyclins D1 and E and cyclin
      dependent kinase inhibitors p16 and p21 in human bowel mucosa.
AB  - AIM: To evaluate whether the cellular proliferation rate in the large bowel
      epithelial cells is characterized by circadian rhythm. METHODS: Between January
      2003 and December 2004, twenty patients who were diagnosed as suffering from
      primary, resectable, non-metastatic adenocarcinoma of the lower rectum,
      infiltrating the sphincter mechanism, underwent abdominoperineal resection, total
      mesorectal excision and permanent left iliac colostomy. In formalin-fixed and
      paraffin-embedded biopsy specimens obtained from the colostomy mucosa every six
      hours (00:00, 06:00, 12:00, 18:00 and 24:00), we studied the expression of G(1)
      phase cyclins (D(1) and E) as well as the expression of the G(1) phase cyclin
      dependent kinase (CDK) inhibitors p16 and p21 as indicators of cell cycle
      progression in colonic epithelial cells using immunohistochemical methods.
      RESULTS: The expression of both cyclins showed a similar circadian fashion
      obtaining their lowest and highest values at 00:00 and 18:00, respectively
      (P<0.001). A circadian rhythm in the expression of CDK inhibitor proteins p16 and
      p21 was also observed, with the lowest levels obtained at 12:00 and 18:00
      (P<0.001), respectively. When the complexes cyclins D(1) -p21 and E-p21 were
      examined, the expression of the cyclins was adversely correlated to the p21
      expression throughout the day. When the complexes the cyclins D(1) -p16 and E-p16
      were examined, high levels of p16 expression were correlated to low levels of
      cyclin expression at 00:00, 06:00 and 24:00. Meanwhile, the highest expression
      levels of both cyclins were correlated to high levels of p16 expression at 18:00.
      CONCLUSION: Colonic epithelial cells seem to enter the G(1) phase of the cell
      cycle during afternoon (between 12:00 and 18:00) with the highest rates obtained
      at 18:00. From a clinical point of view, the present results suggest that G(1) 
      phase specific anticancer therapies in afternoon might maximize their anti-tumor
      effect while minimizing toxicity.

PMID- 16610067
TI  - Portal vein thrombosis: prevalence, patient characteristics and lifetime risk: a
      population study based on 23,796 consecutive autopsies.
AB  - AIM: To assess the lifetime cumulative incidence of portal venous thrombosis
      (PVT) in the general population. METHODS: Between 1970 and 1982, 23,796
      autopsies, representing 84% of all in-hospital deaths in the Malmo city
      population, were performed, using a standardised protocol including examination
      of the portal vein. PVT patients were characterised and the PVT prevalence at
      autopsy, an expression of life-time cumulative incidence, assessed in high-risk
      disease categories and expressed in terms of odds ratios and 95% CI. RESULTS: The
      population prevalence of PVT was 1.0%. Of the 254 patients with PVT 28% had
      cirrhosis, 23% primary and 44% secondary hepatobiliary malignancy, 10% major
      abdominal infectious or inflammatory disease and 3% had a myeloproliferative
      disorder. Patients with both cirrhosis and hepatic carcinoma had the highest PVT
      risk, OR 17.1 (95% CI 11.1-26.4). In 14% no cause was found; only a minority of
      them had developed portal-hypertension-related complications. CONCLUSION: In this
      population-based study, PVT was found to be more common than indicated by
      previous clinical series. The markedly excess risk in cirrhosis and hepatic
      carcinoma should warrant an increased awareness in these patients for whom
      prospective studies of directed intervention might be considered.

PMID- 16610068
TI  - Effects of hypobaric hypoxia on adenine nucleotide pools, adenine nucleotide
      transporter activity and protein expression in rat liver.
AB  - AIM: To explore the effect of hypobaric hypoxia on mitochondrial energy
      metabolism in rat liver. METHODS: Adult male Wistar rats were exposed to a
      hypobaric chamber simulating 5,000 m high altitude for 23 h every day for 0 (H0),
      1 (H1), 5 (H5), 15 (H15) and 30 d (H30) respectively. Rats were sacrificed by
      decapitation and liver was removed. Liver mitochondria were isolated by
      differential centrifugation program. The size of adenine nucleotide pool (ATP,
      ADP, and AMP) in tissue and mitochondria was separated and measured by high
      performance liquid chromatography (HPLC). The adenine nucleotide transporter
      (ANT) activity was determined by isotopic technique. The ANT total protein level
      was determined by Western blot. RESULTS: Compared with H0 group, intra
      mitochondrial ATP content decreased in all hypoxia groups. However, the H5 group
      reached the lowest point (70.6%) (P<0.01) when compared to the control group.
      Intra-mitochondrial ADP and AMP level showed similar change in all hypoxia groups
      and were significantly lower than that in H0 group. In addition, extra
      mitochondrial ATP and ADP content decreased significantly in all hypoxia groups.
      Furthermore, extra-mitochondrial AMP in groups H5, H15 and H30 was significantly
      lower than that in H0 group, whereas H1 group had no marked change compared to
      the control situation. The activity of ANT in hypoxia groups decreased
      significantly, which was the lowest in H5 group (55.7%) (P<0.01) when compared to
      H0 group. ANT activity in H30 group was higher than in H15 group, but still lower
      than that in H0 group. ANT protein level in H5, H15, H30 groups, compared with H0
      group decreased significantly, which in H5 group was the lowest, being 27.1% of
      that in H0 group (P<0.01). ANT protein level in H30 group was higher than in H15
      group, but still lower than in H0 group. CONCLUSION: Hypobaric hypoxia decreases
      the mitochondrial ATP content in rat liver, while mitochondrial ATP level
      recovers during long-term hypoxia exposure. The lower level of extra
      mitochondrial ATP may be related to the decrease of ANT activity during hypoxia
      exposure.

PMID- 16610070
TI  - Adult intussusception caused by cystic lymphangioma of the colon: a rare case
      report.
AB  - We experienced a case of intussusception caused by cys- tic lymphangioma of the
      colon in a 32 years old female who was admitted to our hospital for the chief
      complaint of bloody stool. In the colonoscopic examination, cystic mass with
      stalk which had smooth mucosal surface was noted at the descending colon.
      Abdominal ultrasonography and computed tomography revealed left colon
      intussusception with a multilocular cystic tumor as a leading point. Emergent
      operation was performed. On the histopathologic examination, the cystically
      dilated spaces lined by endothelium and septated by fibrous septa were present.
      The pathological diagnosis was cystic lymphangioma of the colon. Although
      intussusception due to lymphangioma in an adult are rare, it should be taken into
      consideration that it is possible diagnosis.

PMID- 16610069
TI  - Liver cell adenoma: a case report with clonal analysis and literature review.
AB  - We report a case of liver cell adenoma (LCA) in a 33-year-old female patient with
      special respect to its clonality status, pathogenic factors and differential
      diagnosis. The case was examined by histopathology, immunohistochemistry and a
      clonality assay based on X-chromosomal inactivation mosaicism in female somatic
      tissues and polymorphism at androgen receptor focus. The clinicopathological
      features of the reported cases from China and other countries were compared. The
      lesion was spherical, sizing 2 cm in its maximal dimension. Histologically, it
      was composed of cells arranged in cords, most of which were two-cell-thick and
      separated by sinusoids. Focal fatty change and excessive glycogen storage were
      observed. The tumor cells were round or polygonal in shape, resembling the
      surrounding parenchymal cells. Mitosis was not found. No portal tract, central
      vein or ductule was found within the lesion. The tumor tissue showed a positive
      reaction for cytokeratin (CK) 18, but not for CK19, vimentin, estrogen and
      progesterone receptors. Monoclonality was demonstrated for the lesion, confirming
      the diagnosis of an LCA. Clonality analysis is helpful for its distinction from
      focal nodular hyperplasia.

PMID- 16610071
TI  - Spontaneous rupture of splenic hamartoma in a patient with hepatitis C virus
      related cirrhosis and portal hypertension: a case report and review of the
      literature.
AB  - Spontaneous rupture is a rare complication of splenic hamartoma. A review of the
      literature revealed only four such cases. To the best of our knowledge, this is
      the first report of spontaneous rupture of splenic hamartoma associated with
      liver cirrhosis and portal hypertension. A 53-year-old woman, who was followed up
      for aortic dissection and hepatitis C virus (HCV)-related liver cirrhosis, was
      referred with sudden left chest and shoulder pain. An abdominal ultrasound showed
      intraabdominal bleeding, and computed tomography indicated rupture of a splenic
      tumor. Emergent splenectomy was carried out. The postoperative course was
      uneventful, and the patient was discharged on the 13th postoperative day.
      Pathology revealed the tumor to be a ruptured splenic hamartoma. The non-tumorous
      splenic parenchyma revealed congestive changes. We consider that the presence of
      liver cirrhosis and portal hypertension are risk factors for spontaneous rupture
      of the splenic hamartoma.

PMID- 16610072
TI  - A case of primary biliary cirrhosis complicated by Behcet's disease and
      palmoplantar pustulosis.
AB  - A 46-year-old woman was diagnosed with palmoplantar pustulosis (PPP) at the
      Department of Dermatology, Fukushima Medical University Hospital in 2000, and was
      treated with ointment. However, because liver dysfunction developed in 2003, she
      was referred to our department, where primary biliary cirrhosis (PBC) was also
      diagnosed on the basis of clinical findings. One year later, at the age of 49,
      she developed manifestations of Behcet's disease (BD), including erythema nodosum
      in the lower extremities. Because she had a history of uveitis, recurrent oral
      ulceration was present, and the HLA typing was positive for B51, BD was
      additionally diagnosed. Liver function normalized within three months of the
      start of treatment with ursodesoxycholic acid (UDCA). This is the first case of
      PBC associated with BD and PPP.

PMID- 16610073
TI  - Chest wall metastasis from unknown primary site of hepatocellular carcinoma.
AB  - Previous reports of a solitary metastatic hepatocellular carcinoma have been
      rare. Because this tumor has a different treatment modality and prognosis, an
      accurate differential diagnosis is essential. Here we report a rare case of a
      solitary chest wall metastasis from unknown primary site of hepatocellular
      carcinoma. It involves a 51-year-old man who was admitted to our hospital because
      of a palpable left upper chest wall mass. The mass was resected and pathologic
      examination confirmed a diagnosis of metastatic hepatocellular carcinoma. Despite
      our investigation, no evidence was found that indicated the primary origin of the
      hepatocellular carcinoma. Four months later, the patient was admitted again
      because of spinal cord compression at the third and fourth thoracic vertebrae.
      Emergent decompressive laminectomy was performed and microscopic features
      revealed the same pathology as the initial chest wall mass resected 4 months
      earlier. After one year, a follow-up abdominal computed tomography (CT) still
      revealed no evidence of primary hepatocellular carcinoma.

PMID- 16610074
TI  - [Current advances in myelodysplastic syndrome].

PMID- 16610075
TI  - [Study on unrelated donor allogeneic bone marrow transplantation with Bu-CY2
      conditioning regimen for myelodysplastic syndrome].
AB  - OBJECTIVE: To evaluate the efficacy and safety of Bu-CY(2) conditioning regimen
      on allogeneic bone marrow transplantation (BMT) with unrelated donor for
      myelodysplastic syndrome. METHODS: Six patients received chemotherapy regimen of
      busulfan (Bu) and cyclophosphamide (CY) before allogeneic BMT (Bu 4 mg . kg(-1) .
      d(-1), -7 d - -4 d, CY 60 mg . kg(-1) . d(-1), -3 d - -2 d). Mycophenolate
      mofetil combined with cyclosporin A and methotrexate was used for prevention of
      acute graft-versus-host disease after transplantation. Lipo prostaglandin E(1)was
      used in prophylactic regimen for hepatic veno-occlusive disease. RESULT:
      Neutrophil count began to be higher than 0.5 x 10(9)/Lat the 18th day after BMT.
      Platelet count began to be higher than 20 x 10(9)/Lat the 21st day after BMT.
      Disease-free survival in the six patients was 27 months. CONCLUSION: Bu-CY(2)
      conditioning regimen on allogeneic bone marrow transplantation with unrelated
      donor is an effective therapy for patients with myelodysplastic syndrome.

PMID- 16610076
TI  - [Inhibition effect of topotecan on human myelodysplastic syndrome cells in vitro
      and in vivo].
AB  - OBJECTIVE: To investigate the effect of topotecan (TPT) on human myelodysplastic
      syndrome (MDS) cells in vitro and in vivo. METHODS: Cell growth was measured by a
      MTT assay. The percentage of cells undergoing apoptosis was determined by flow
      cytometry after staining with annexin V-FITC and propidium iodide. The morphology
      of apoptotic cells was observed by transmission electron microscopy (TEM).
      Furthermore, the antitumor effect on MDS cells in xenotransplanted severe
      combined immunodeficiency (SCID) mice was evaluated by tumor volume and survival.
      Western blot was used for determining the expression of topoisomerase I (Top1)
      protein. RESULT: The growth of Mutz-1 cells was suppressed by TPT treatment in a
      dose-dependent manner. The 50% inhibition in Mutz-1 cell growth (IC(50)) of TPT
      for 72 h was 272 ng/L. The percentage of apoptotic cells observed in the Mutz-1
      cells after exposure to TPT (160 ng/L) in 48 h and 72 h was (54.16 +/-4.29)% and
      (72.97+/-6.12)%, respectively. TEM showed the characteristics of apoptosis in
      Mutz-1 cells treated with TPT. The xenotransplanted SCID mice treated with TPT
      showed inhibited tumor growth compared with control group. TPT treatment resulted
      in a longer survival as compared with the control group (P<0.001) and with the
      As2O3-treated group (P<0.001). The cells exposed to TPT exhibited a time
      dependent decrease of Top1 protein expression. CONCLUSION: TPT can inhibit Mutz-1
      cell growth and induce apoptosis in vitro.The downregulation of Top1 may be
      involved in the apoptosis induced by TPT. TPT has a significant antitumor effect
      in vivo.

PMID- 16610077
TI  - [WT1 gene expression in myelodysplastic syndrome and its clinical implication].
AB  - OBJECTIVE: To investigate the expression of WT1 gene in myelodysplastic syndrome
      (MDS) and to explore its clinical implications. METHODS: Expression of WT1 mRNA
      was detected in 53 patients with myelodysplastic syndrome and 10 healthy subjects
      by reverse transcriptase polymerase chain reaction (RT-PCR). RESULT: WT1 gene was
      expressed in all MDS patients. The positive rate and expression level in MDS
      patients were higher than those in healthy subjects. The positive rates of WT1
      expression in MDS-RAEB and MDS-RAEB-t groups were higher than those in MDS-RA and
      MDS-RAS groups. The expression level was gradually increased from MDS-RA and MDS
      RAS groups to MDS-RAEB and MDS-RAEB-t groups. CONCLUSION: The expression of WT1
      gene might be associated with the development of MDS, and it can be used for risk
      assessment and monitor of disease progression and therapeutic effects in MDS
      patients.

PMID- 16610078
TI  - [Inhibition effect of fludarabine on the growth of myelodysplastic syndrome cell
      line MUTZ-1 and its mechanism].
AB  - OBJECTIVE: To investigate the inhibition effect of fludarabine on the growth of
      human MDS-RAEB cell line MUTZ-1 and to explore the possible cellular and
      molecular mechanism. METHODS: The apoptosis of MUTZ-1 cells induced by
      fludarabine was studied by transmission electron microscope, MTT assay, DNA
      ladder test, flow cytometry and RT-PCR method. RESULT: Treatment with fludarabine
      remarkably inhibited the growth of MUTZ-1 cells, the 24 h IC(50), 48 h IC(50) and
      72 h IC(50) of fludarabine for MUTZ-1 cells were 137.65 mg/L, 6.27 mg/L and 0.51
      mg/L, respectively. Fludarabine inhibited the growth of MUTZ-1 cells in a dose
      dependent and time-dependent manner. After treated by fludarabine (1 mg/L-16
      mg/L)for 24 h, MUTZ-1 cells showed the typical features of apoptosis. After
      fludarabine treatment the mRNA expression of Bcl-2, Bax, survivin, XIAP, cIAP-1
      and cIAP-2 was not changed, but the mitochondrial membrane potential (MMP) was
      decreased. CONCLUSION: With a certain range of dose fludarabine (1 mg/L-16
      mg/L)could inhibit MUTZ-1 cell growth by inducing cells apoptosis. MMP may play a
      certain role in apoptosis of MUTZ-1 cells induced by fludarabine.

PMID- 16610079
TI  - [Karyotype analysis of 283 cases of myelodysplastic syndrome].
AB  - OBJECTIVE: To explore the implication of karyotype analysis in diagnosis and
      prognosis of myelodysplastic syndrome (MDS). METHODS: The chromosomes were
      prepared with direct method, brief culture of cells and R-banding techniques, and
      then the karyotypic analysis was performed. RESULT: Seventy-seven out of 283
      patients (27.21%) had karyotypic abnormalities, including the numeral
      abnormalities of chromosomes and structural alterations. The most common
      chromosomal aberrations were +8, -20/20q-, -Y, translocation, -7/7q-, +9, -5/5q-.
      The rate of abnormal karyotype in refractory anemia with erythroblasts (RAEB) and
      refractory anemia erythroblasts-transformation (RAEB-t) was much higher than in
      refractory anemia (RA). Patients with abnormal karyotype or higher IPSS scores
      had a higher risk of transformation into acute leukemia than patients with normal
      karyotype or lower IPSS scores (P<0.05). CONCLUSION: MDS is a highly heterogenous
      disorder and karyotype analysis is helpful for its diagnosis and prognosis
      estimation.

PMID- 16610080
TI  - [Homeostatic conditions affect the protective effect of edaravone on ischemic
      injury in neurons].
AB  - OBJECTIVE: To determine whether homeostatic conditions (pH, glycine or ion
      concentration) affect the protective effects of edaravone on ischemic injury in
      rat cortical neurons. METHODS: In cultured rat cortical neurons, the compositions
      in the experimental solutions were changed to mimic the disturbance of
      homeostasis after cerebral ischemia. In vitro ischemic injury was induced by
      oxygen-glucose deprivation (OGD) for 3 h and reperfusion for 12 h, and the neuron
      injury was evaluated by 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium
      bromide (MTT) reduction assay and lactate dehydrogenase (LDH) release. Effect of
      edaravone on OGD injury was observed in different experimental solutions. RESULT:
      In weak alkalified solution (pH 7.8) or the solution containing glycine (10
      micromol/L), OGD injury became more serious; but in weak acidic (pH 6.5) or
      higher Mg(2+) (1.8 mmol/L) solutions, OGD injury was attenuated. Edaravone (1
      micromol/L) reversed the injury in the solutions with pH 6.1,7.4 and 7.8 or the
      solution containing glycine, but did not show protective effect in the solution
      with pH 6.5 and the higher Mg(2+) or lower Ca(2+) solution. CONCLUSION: The
      changes of homeostatic conditions affect the severity of ischemic injury of
      neurons and the protective effect of edaravone.

PMID- 16610081
TI  - [Application of PCR-based tRNAval Pol III-shRNA expression cassettes in screening
      of efficient siRNA for inhibiting hepatitis B virus].
AB  - OBJECTIVE: To screen efficient siRNA for inhibiting hepatitis B virus using the
      technique of PCR-based tRNA(val) Pol III-shRNA expression cassettes (SECs).
      METHODS: Based on core gene sequence of HBV, five target sites of siRNA were
      designed. tRNAval Pol III-shRNA expression cassettes produced by one-step
      overlapping extension PCR strategy were co-transfected with HBV C gene and pC
      EGFP plasmid into AD293 cells respectively. Forty-eight hours after transfection,
      fluorescence of HBVC-GFP protein was detected by fluorescence-activated cell
      sorting (FACS); HBV C mRNA was detected by semi-quantitative RT-PCR. HBV
      producing HepG2. 2. 15 cells were transfected with selected SECs for 72 h, HBsAg
      and HBeAg in the cell culture medium were detected by radioimmunoassay assay
      (RIA). HBV pgRNA from cell total RNA was detected by semi-quantitative PCR.
      RESULT: Co-transfection with pC-GFP plasmid and SECs into AD293 cells resulted in
      inhibition expression of HBV C gene and decrease of EGFP fluorescence intensity.
      SEC-492i showed most significant inhibition effect on HBV C-EGFP expression
      compared with other SECs. Selected SEC-492i or SEC-282i targeting core gene could
      efficiently decrease expression of HBeAg and the level of HBV pgRNA in a dose
      dependent manner. SEC-492i inhibited HBV replication and antigen expression in a
      more efficient way than SEC-282i at the same final concentration. CONCLUSION: The
      expressed shRNA, which targets sites on HBV C mRNA in 492i, is to have having
      most efficient RNAi effect. tRNAval Pol III-shRNA expression cassettes produced
      by one-step overlapping extension PCR strategy should be useful for
      identification of optimal siRNA.

PMID- 16610082
TI  - [Effects of bFGF and alpha-MSH on adhesion and migration of human melanocytes in
      vitro].
AB  - OBJECTIVE: To observe the effect of basic fibroblast growth factor (bFGF) and
      alpha-melanocyte stimulating hormone (alpha-MSH) on adhesion and migration of
      melanocytes in vitro. METHODS: Human melanocytes were obtained from normal human
      foreskins. Culture dishes covered with fibronectin were used to perform
      melanocytes adhesion assay, and cell motility was assessed using the Transwell
      micropore filter method. RESULT: bFGF and alpha-MSH increased melanocytes
      adhesion on culture dishes covered with fibronectin. bFGF stimulated melanocytes
      migration through micropore filter while alpha-MSH had no significant effects.
      CONCLUSION: bFGF and alpha-MSH could promote the adhesion and migration of
      melanocytes, which suggests that two agents may play a role in the repigmentation
      of vitiligo.

PMID- 16610083
TI  - [COX-2 mediates U50488H-induced delayed cardioprotection in isolated rat heart].
AB  - OBJECTIVE: To determine whether U50488H, a selective agonist of kappa-opioid
      receptor, could induce biphasic (early and late) cardioprotection against
      myocardial ischemia/reperfusion injury and to explore the underlying mechanisms.
      METHODS: Isolated perfused rat hearts were subjected to 30 min of ischemia
      followed by 120 min reperfusion and the cardiac function was evaluated. RESULT:
      Left ventricular end-diastolic pressure (LVEDP), left ventricular developed
      pressure (LVDP) and maximal velocity of contraction and relaxation (+/-dP/dtmax)
      were improved when U50488H was administered 1 or 24 h before ischemia (P<0.05).
      Myocardial infarct size, activities of creatine kinase (CK) and lactate
      dehydrogenase (LDH) in the coronary effluent were lower in the U50488H
      pretreatment group than those in the control group. Administration of a selective
      cyclooxygenase-2 (COX-2) inhibitor, celecoxib abolished the late phase of
      cardioprotection produced by administration of U50488H 24 h before ischemia.
      Activities of CK and LDH in the coronary effluent were higher in U50488H and
      celecoxib co-pretreatment group than those in U50488H group. However,
      administration of celecoxib did not block the early phase of cardioprotection by
      1 h treatment of U50488H before ischemia. CONCLUSION: The late (but not the
      early) phase of cardioprotection induced by kappa-opioid receptor agonist might
      be mediated by COX-2.

PMID- 16610084
TI  - [Roles of the central nucleus of amygdala in the cardiovascular response elicited
      by the paraventricular nucleus of hypothalamus].
AB  - OBJECTIVE: To investigate the cardiovascular responses induced by activation of
      the paraventricular nucleus of hypothalamus (PVN) and the roles of the central
      nucleus of amygdala (CeA) on this effect. METHODS: The PVN was activated by
      microinjection of L-glutamate or electrical stimulation. The CeA was injected
      with L-glutamate or Kainic acid (KA). The femoral arterial pressure, mean
      arterial pressure (MAP), electrocardiogram (ECG) and heart rate (HR) of the male
      SD rats were recorded when the PVN was electrically stimulated. RESULT: The blood
      pressure increased when the PVN was activated either by electrical current or by
      L-glutamate. The blood pressure increased for (10.27+/-1.80)mmHg and the change
      of heart rate was -10.66 +/- 8.11 beat/min after L-Glu (100 nl) was injected into
      the ipsilateral CeA. The pressor response of PVN stimulation could still be
      evoked by electrical stimulation of (13.78 +/- 3.18)mmHg 10 min after kainic acid
      (100 nl) was injected into the ipsilateral CeA. But this pressor response
      decreased of 6.57 mmHg compared to that before injection of KA (P <0.05). The
      locations of the electrode tips and termination of the injector tracts were
      identified according to the atlas after the recording. CONCLUSION: Stimulating
      the PVN elicits pressor response in rats. The CeA mediates partly the pressor
      response elicited by activation of the PVN.

PMID- 16610085
TI  - [Effect of cinobufacini on vascular contractile of rat thoracic aorta].
AB  - OBJECTIVE: To examine the effect of cinobufacini on rat thoracic aorta and its
      mechanism. METHODS: Isolated rat thoracic aorta was perfused and isometric
      tension was recorded by organ bath technique before and after cinobufacini
      treatment. RESULT: Cinobufacini induced contraction of isolated thoracic aorta
      with or without endothelium in a concentration-dependent manner (at concentration
      of 2.5,5.0,7.5,10.0 g/L). The vasoconstriction effect of cinobufacini was more
      potent in endothelium-denuded aorta ring [(16.3+/-3.39)%, (52.5+/-7.70)%, (60.9+/
      8.84)%, (69.2+/-11.34)%] than in endothelium-intact aorta ring [(6.2+/-2.07)%,
      (14.7+/-4.91), (17.6+/-5.86)%, (20.3+/-6.78)% (P<0.01)]. Its contractile effect
      was attenuated in Ca(2+)-free solution (about 1/10 of that in buffer with 1.25
      mmol/L CaCl(2)) or by the treatment with verapamil (10(-7)mol/L), an L-type
      calcium channel antagonist. Cinobufacini induced contraction on the endothelium
      intact rat aorta was augmented by pretreatment with L-NAME (10(-4)mol/L), a
      nitric oxide synthase inhibitor. CONCLUSION: Cinobufacini contracts rat thoracic
      aorta by opening the voltage-dependent Ca(2+) channel and increasing Ca(2+)
      influx into vascular smooth muscle. Cinobufacini can also stimulate the release
      of vascular relaxant factor, nitric oxide, from the endothelium and thus
      antagonize cinobufacini-induced contraction.

PMID- 16610086
TI  - [Acitretin induces apoptosis and changes of relative signaling pathway in
      epidermoid carcinoma cell line A431].
AB  - OBJECTIVE: To study the effects of Acitretin on growth inhibition and apoptosis
      of epidermoid carcinoma cell line A431 and its molecular mechanisms. METHODS:
      A431 cells were treated with Acitretin at the concentration of 10(-5)mol/L in
      different time intervals. The inhibition of cell growth was determined by MTT
      method, morphological changes were observed by electron microscopy, apoptosis was
      assessed by flow cytometry and Annexin-V staining. The mRNA expression levels of
      STAT3, cyclinD1 and p42/44MAPK were detected by reverse transcriptase polymerase
      chain reaction (RT-PCR). The protein expression levels of P-STAT3 and CyclinD1
      were observed by Western blot in A431 cells. RESULT: (1)Acitretin inhibited the
      growth of A431 cells in vitro in a dose-and time-dependent manner. Morphological
      changes revealed characteristics of cell apoptosis. Flow cytometry showed more
      sub-G(1) phase in A431 cells and more cells positively stained with Annexin-V.
      (2)Acitretin significantly inhibited the expression of STAT3 and CyclinD1 mRNA in
      A431 cells in vitro in a time-dependent manner(P<0.05). The p-STAT3 and CyclinD1
      protein levels were down regulated. The Acitretin could also down regulate the
      p42/4MAPK mRNA in A431 cells. (3) After incubation with Acitretin, the mRNA level
      of CyclinD1 in A431 cells was positively correlated with that of STAT3(p<0.05).
      The protein level of CyclinD1 was also positively correlated with that of p
      STAT3(p<0.05). However, there was no correlation between Mrna levels of CyclinD1
      and p42/44MAPK. CONCLUSION: (1)Acitretin plays an inhibitory role in the tumor
      cell growth and induces the cell apoptosis in A431 cells. (2)The regulation of
      the Jak/STAT3 signaling pathway may play an important role in inducing growth
      inhibition and apoptosis by Acitretin in A431 cells.

PMID- 16610087
TI  - [Study of paroxysmal kinesigenic dyskinesia with fMRI].
AB  - OBJECTIVE: To detect the differences in subcortical structures between patients
      with paroxysmal kinesigenic dyskinesia (PKD) and normal subjects during movement
      preparation and execution. METHODS: The PKD patients performed a movement task,
      in which a CUE signal (preparation) indicated the movement sequence prior to the
      appearance of an imperative GO signal (execution). Event-related functional
      magnetic resonance imaging (fMRI) and 3dDeconvolve program of AFNI were used to
      estimate the hemodynamic response function and to generate activation maps.
      RESULT: During movement preparation, the activated brain areas in PKD patients
      were less than those of normal subject, and there was no activation in basal
      ganglia in PKD patients. During execution, the activation was also less in PKD
      patients except in bilateral M1. CONCLUSION: During intermission, abnormalities
      of the brain still exist in PKD patients when during preparing or performing
      movement. The movement circuit in the brain displays an unusual state. The attack
      may be caused by reducing of inhibition in brain areas.

PMID- 16610088
TI  - [Relationship of angiopoietins expression with microvessel density (MVD) in human
      colorectal tumors].
AB  - OBJECTIVE: To investigate the expression of angiopoietin (Ang)-1 and Ang-2 in
      colorectal tumors and its relations to microvessel density (MVD) in tumor tissue.
      METHODS: Ang-1, Ang-2 and factor VIII-related antigen were stained
      immunohistochemically in 91 cases of primary colorectal adenocarcinoma, 20 cases
      of colorectal adenoma and 24 cases of normal colorectal mucosal tissue, and MVD
      was also assayed in above tissue specimens. RESULT: (1) A significantly higher
      Ang-1 (7.07+/-2.00) was observed in normal tissue compared with 1.75 +/-1.98 in
      the adenoma and 1.40 +/- 1.22 in the adenocarcinoma (P<0.01). (2) Ang-2 protein
      positive rate in adenocarcinoma was significantly higher than that in normal
      tissue and adenoma (P<0.01). The expression of Ang-2 in adenocarcinoma was
      closely associated with poor differentiation and vessel invasion. (3) There were
      significant correlations between Ang-1 and Ang-2 (r=-0.338, P<0.01), Ang-1 and
      MVD (r=-0.388, P<0.01), Ang-2 and MVD (r=0.594, P<0.01) in the 135 cases.
      CONCLUSION: The overexpression of Ang-2 may play an important role in
      angiogenesis of colorectal adenocarcinoma. It can be regarded as an index for
      malignancy and prognosis in colorectal adenocarcinoma.

PMID- 16610089
TI  - [Prediction of human intestinal absorption from net polar atomic charges of drug
      molecules].
AB  - OBJECTIVE: To predict human intestinal absorption and permeability coefficients
      in Caco-2 cell monolayers from net polar atomic charges of drug molecules.
      METHODS: The net atomic charges and the volumes of drug molecules were obtained
      with the semiempirical self-consistent field molecular orbital calculation CNDO/2
      method and Mont Carlo method respectively, using the minimum energy conformation
      obtained from the optimization of the standard molecular geometry with the
      molecular mechanics MM+ method. The stepwise multiple regression analysis was
      used to obtain the correlation equations. RESULT: Both percent of human
      intestinal absorption and permeability coefficients in Caco-2 cell monolayers of
      drug molecules were well correlated with the sum of the net atomic charges of all
      hydrogen-bonding donors (sigmaQH) and the sum of the net atomic charges of all
      hydrogen-bonding acceptors (sigmaQN, 0). The more the net positive atomic charges
      of hydrogen-bonding donors and the net negative atomic charges of hydrogen
      bonding acceptors, the less were the percent human intestinal absorption and
      permeability coefficients in Caco-2 cell monolayers of drug molecules.
      CONCLUSION: Drug absorption in human intestines is closely related with its
      hydrogen-bonding potential. The drug molecules with weaker hydrogen-bonding
      potential have greater percent human intestinal absorption. The net polar atomic
      charges can be computed simply, so they can be used in high throughput screening
      of oral drugs.

PMID- 16610090
TI  - [Expression of survivin mRNA in HHT-induced cell apoptosis of hematological
      malignancy cell lines].
AB  - OBJECTIVE: To investigate the expression of survivin mRNA in hematological
      malignancy cells and its correlation with HHT-induced cell apoptosis. METHODS:
      Hematological malignancy cell lines MUTZ-1, K562, Jurkat, RPMI and HL60 were
      treated with HHT in vitro. Cell apoptosis was observed by flow cytometry (FCM)
      and the expression of surviving and XIAP mRNA was evaluated with semi
      quantitative RT-PCR. RESULT: The expression of survivin mRNA on cell lines was
      negatively correlated to HHT-induced cell apoptotic rate (r=-0.980, P=0.003).
      There were no significant differences in XIAP expression among these 5 cell
      lines. CONCLUSION: Survivin could be used as a new marker for drug-sensitivity
      and a new target for treatment of hematological malignancies.

PMID- 16610091
TI  - [Effects of berbamine on growth of leukemia cell line NB4 and its mechanism].
AB  - OBJECTIVE: To determine effects of berbamine on the growth of leukemia cell line
      NB4 and explore its possible mechanisms. METHODS: The growth of NB4 cells was
      examined with MTT assay. Morphological analysis and DNA agarose electrophoresis
      were used to detect apoptosis in NB4 cells, and the apoptosis rate was measured
      by flow cytometry. The PML/RAR alpha mRNA was determined by nested-PCR, and the
      Survivin mRNA was tested by RT-PCR. The expression of caspase 3 protein in NB4
      cells was evaluated by flow cytometry. RESULT: The growth of NB4 cells was
      inhibited significantly after treated with berbamine at different concentrations
      for different time points, the IC(50)value was 3.860 microg/ml at 48 hours.
      Morphology analysis showed the characteristics of apoptosis, and the DNA agarose
      electrophoresis showed the typical DNA ladder. The apoptosis rate increased from
      2.83% to 58.44% after treated with berbamine at 12 microg/ml for 48 hours. The
      expression of PML/RAR alpha mRNA presented no significant changes, however,
      Survivin mRNA was decreased dramatically. The protein expression of Caspase 3
      increased significantly from 2.06% to 70.89% after treated with berberine at a
      concentration of 12 mug/ml for 48 hours. CONCLUSION: Berbamine could inhibit the
      growth of leukemia cell line NB4. The induction of cell apoptosis may be one of
      the mechanisms for suppressing the growth of leukemia cell line NB4. Inhibition
      of Survivin mRNA and upregulation of Caspase 3 protein might be also involved in
      cell apoptosis.

PMID- 16610092
TI  - [Relationship between cerebral vasospasm and delayed ischemic neurological
      deficit].
AB  - OBJECTIVE: To investigate the relationship between cerebral vasospasm and
      occurrence of delayed ischemic neurological deficit (DIND). METHODS: The clinical
      records and radiographic images of 118 patients with subarachnoid hemorrhage
      admitted during last 5 years were reviewed. The incidence,degree and localization
      of cerebral vasospasm were evaluated, and morbidity of related DIND was analyzed.
      Patients with cerebral vasospasm were divided into three groups: Group MCA
      (middle cerebral artery), Group ACA (anterior cerebral artery) and Group ICA
      (intracranial carotid artery) according to the location of cerebral vasospasm.
      The consistency of DIND and image of cerebral infarction were examined. RESULT:
      There was a weak correlation between cerebral vasospasm and incidence of DIND
      (r=0.22; P=0.016). The incidence of DIND was increased with severity of cerebral
      vasospasm (U=2.589, P<0.05). The group MCA had a significantly higher incidence
      of DIND than that of ACA and ICA groups (68.0% compared with 36.7% and 25.0%,
      respectively, chi(2)=8.195, P=0.004), the difference between later two groups was
      not statistically significant (chi(2)=0.646, P=0.421). CONCLUSION: Cerebral
      vasospasm may be an important factor leading to DIND occurrence; the severity and
      location of cerebral vasospasm is related to the incidence of DIND.

PMID- 16610093
TI  - [Purification of total flavones from Morus alba L.by macroporous adsorbents and
      kinetic model for the process].
AB  - OBJECTIVE: To establish the separation and purification technology for the total
      flavones from Morus alba L.(MTF), and present a kinetic model for this process.
      METHODS: Three types of macroporous adsorbents were tested to separate and purify
      MTF, and to evaluated by adsorption capacity, elution ratio and product purity.
      The curves of dynamic adsorption-elution process was plotted and the kinetic
      equations were presented. RESULT: Among three types of macroporous adsorbents,
      the NKA-9 type showed better property with the adsorption capacity of 43.4 mg.g(
      1)and the elution ratio of 98.2%. The purity of MTF product reached to 58.2 % in
      the technological conditions following: extract sample concentration of 20 mg.ml(
      1), 6 times washing water and elution reagent of 70% ethanol. The adsorbent could
      be used for 4 times repeatedly. The kinetic equation was y=u(1 - e(-kx)).
      CONCLUSION: The NKA-9 type of macroporous absorbent is suitable to purify the
      MTF.

PMID- 16610094
TI  - [Inhibitory effects of mizolastine on substance P-induced production of
      leukotriene B4 and interleukin 5 in mouse skin].
AB  - OBJECTIVE: To observe the inhibitory effect of mizolastine on substance P(SP)
      induced production of leukotriene B(4) (LTB(4)) and interleukin 5 (IL-5) in mouse
      skin. METHODS: Mice were fed with different doses of mizolastine or other control
      drugs, 30 min after administration animals were injected intradermally with SP on
      the back. The treated skin samples were taken and competitive enzyme-link
      immunoassay (ELISA) method was applied to detect LTB (4) and IL-5 in the skin
      samples. RESULT: The LTB(4) and IL-5 levels in 10 mg/kg mizolastine group were
      (1.23 +/-0.29)pg/ml and (34.28 +/-11.00)pg/ml, respectively, which were lower
      than those in saline control group [(5.52+/-1.88)pg/ml and (179.62 +/-46.25)pg/ml
      respectively] or loratadine group [(3.89+/-1.27)pg/ml and (127.74 +/-43.27)pg/ml
      respectively]. No significant difference was found between 10 mg/kg mizolastine
      group and dexamethasone group (P=0.161 and P=0.508). CONCLUSION: Mizolastine
      might inhibit the production of LTB(4) and IL-5 induced by substance P in mouse
      skin, suggesting that anti-inflammatory effect and the blockade of histamine H1
      receptors might be involved in its anti-pruritic mechanisms.

PMID- 16610095
TI  - [Current advances in gene diagnosis and therapy of gelatinous drop-like corneal
      dystrophy].
AB  - Gelatinous drop-like corneal dystrophy (GDLD) is an autosomal recessive
      hereditary disease, which may result in bilateral loss of vision. The gene
      responsible for GDLD, M1S1 is mapped on the short arm of chromosome 1 (1p), but
      the possible etiology of this disease remains unclear. Corneal transplantation is
      the only treatment for visual rehabilitation. The detection of the mutations of
      the M1S1 gene and the possible etiological involvement of the amyloid deposits
      are discussed. The current literatures are extensively reviewed in this article.

PMID- 16610096
TI  - Doctors for the world: Indian physician emigration.
AB  - Almost 60,000 Indian physicians practice in the United States, United Kingdom,
      Canada, and Australia--a workforce equal to 10 percent of the physicians in India
      and the largest emigre physician workforce in the world. I traveled to India to
      interview leaders in medical education, health policy, and public health, to
      better characterize and understand Indian physician emigration. A changing
      political and policy environment in India is raising new questions about what
      might be done to keep more of India's physicians at home.

PMID- 16610097
TI  - 'Follow-on biologics': ensuring continued innovation in the biotechnology
      industry.
AB  - Congress adopted legislation in 1984 to encourage pharmaceutical companies to
      develop new drugs, while simultaneously allowing competitors to bring cheaper
      generic versions to market. More than twenty years later, Congress may be faced
      with a similar balancing act for biologics. When Congress takes up this issue, it
      must focus on the substantial differences that exist between biologics and drugs.
      It should also evaluate the patent law, which is yielding increasingly narrow
      patents. If additional measures are not adopted in light of the intersection of
      these factors, then any legislation allowing for "follow-on" biologics could
      stifle development of new medicines from biotechnology.

PMID- 16610098
TI  - Multicolor in vivo time-lapse imaging at cellular resolution by stereomicroscopy.
AB  - Intravital time-lapse imaging has altered significantly many long-standing rules
      of biological mechanisms, but being apparatus-intense and laborious, time-lapse
      imaging remained mostly restricted to specialized labs. We show that recently
      introduced, fully automated fluorescence stereomicroscopes represent cost
      effective but powerful means of imaging dynamic events ranging from observing
      embryogenesis over several days to detailed tissue rearrangements and fast blood
      cell rolling in vivo. When combined with deconvolution approaches, even
      subcellular resolution in several colors can be achieved. Using three-dimensional
      image recording, we show the spatial reconstruction of expression patterns.
      Furthermore, by combining three-dimensional image recording over time with
      subsequent deconvolution analysis, we demonstrate that subcellular dynamics such
      as axonal pathfinding can be resolved. These findings promise that time-lapse
      imaging using a stereomicroscope will become a hands-on standard method for
      phenotype analysis in many fields of biology.

PMID- 16610099
TI  - Assistant professorships and the Swiss National Science Foundation.

PMID- 16610100
TI  - Adults with congenital heart disease.

PMID- 16610101
TI  - Abnormal circuit function in dystonia.

PMID- 16610103
TI  - The future of forensic and crime scene science, June 2005. Centre for Forensic
      Investigation, School of Science & Technology, University of Teesside.

PMID- 16610105
TI  - College on the problems of drug dependence. Highlights from the 67th annual
      meeting.

PMID- 16610102
TI  - Short-term and long-term effects of fatty acids in rat hepatoma AS-30D cells: the
      way to apoptosis.
AB  - Arachidonic acid and, to a smaller extent, oleic acid at micromolar
      concentrations decreased the mitochondrial membrane potential within AS-30D rat
      hepatoma cells cultivated in vitro and increased cell respiration. The uncoupling
      effect of both fatty acids on cell respiration was partly prevented by
      cyclosporin A, blocker of the mitochondrial permeability transition pore.
      Arachidonic acid increased the rate of reactive oxygen species (ROS) production,
      while oleic acid decreased it. Both fatty acids induced apoptotic cell death of
      AS-30D cells, accompanied by the release of cytochrome c from mitochondria to the
      cytosol, activation of caspase-3 and association of proapoptotic Bax protein with
      mitochondria; arachidonic acid being a more potent inducer than oleic acid.
      Trolox, a potent antioxidant, prevented ROS increase induced by arachidonic acid
      and protected the cells against apoptosis produced by this fatty acid. It is
      concluded that arachidonic and oleic acids induce apoptosis of AS-30D hepatoma
      cells by the mitochondrial pathway but differ in the mechanism of their action:
      Arachidonic acid induces apoptosis mainly by stimulating ROS production, whereas
      oleic acid may contribute to programmed cell death by activation of the
      mitochondrial permeability transition pore.

PMID- 16610106
TI  - Soft tissue tumour of the fetal thigh.

PMID- 16610104
TI  - The Drakensberg declaration on the control of rheumatic fever and rheumatic heart
      disease in Africa.

PMID- 16610107
TI  - Animal attacks -- a red herring of child abuse?

PMID- 16610108
TI  - Misunderstanding Muslims.

PMID- 16610109
TI  - HIV special needs plans (SNPs): a new health care option in New York.

PMID- 16610110
TI  - Challenges when starting antiretroviral treatment.

PMID- 16610111
TI  - A comprehensive treatment approach to HIV.

PMID- 16610112
TI  - Factors influencing adherence. Patients said taking personal responsibility for
      their own success was essential, and recommended strategies to keep dosing easy
      and pills accessible.

PMID- 16610113
TI  - It's not only about the pills. If you're changing to a new regimen, don't neglect
      your emotions.

PMID- 16610114
TI  - Maximizing medication benefits with natural therapies.

PMID- 16610115
TI  - Revisiting monotherapy: heresy or revised orthodoxy?
AB  - After the widespread introduction of triple combination antiretroviral therapy in
      1996 caused AIDS deaths to plummet, the earlier practice of single-drug treatment
      -or monotherapy--seemed like an embarrassing phase of medical ignorance. By then,
      it had become all too apparent that monotherapy promoted the rapid development of
      drug-resistant virus, often leading to treatment failure. Stories still
      occasionally surface about an isolated doctor prescribing solo AZT (zidovudine,
      Retrovir), and many long-time HIV physicians with large practices probably have
      one or two patients still doing well on two drugs and see no reason to change
      their regimens. But by and large, hitting hard with two nucleoside reverse
      transcriptase inhibitors (NRTIs) plus either a protease inhibitor (PI) or a non
      NRTI (NNRTI) has become dogma, and is now enshrined in all HIV treatment
      guidelines.

PMID- 16610116
TI  - Nutrition and HIV.
AB  - Good nutrition is key to a healthy lifestyle, regardless of whether one is living
      with HIV/AIDS. Optimal nutrition can help boost immune function, maximize the
      effectiveness of antiretroviral therapy, reduce the risk of chronic illnesses
      such as diabetes and cardiovascular disease, and contribute to a better overall
      quality of life. In the early years of the AIDS epidemic, many people with HIV
      were dealing with wasting and opportunistic infections (OIs) linked to unsafe
      food or water. While these problems are less common today in developed countries
      with widespread access to highly active antiretroviral therapy (HAART), many HIV
      positive people have traded these concerns for worries about body shape changes,
      elevated blood lipids, and other metabolic complications associated with
      antiretroviral therapy. Fortunately, maintaining a healthy diet can help address
      these problems. As HIV positive people live longer thanks to effective treatment,
      good nutrition can also help prevent problems (such as bone loss) associated with
      normal aging. But there is no single, optimal eating regimen appropriate for
      every person living with HIV/AIDS. Instead, HIV positive people should adopt a
      sensible balanced diet and consult an experienced nutrition specialist for
      individualized recommendations.

PMID- 16610117
TI  - Women and HIV. Aging with HIV.
AB  - Several of the physical symptoms and illnesses related to HIV disease and its
      treatment--such as fatigue, weight changes, memory loss, depression, and
      atherosclerosis--mimic typical age-related health problems. It is estimated that
      at least 10% of HIV positive people in the United States are 50 years of age or
      older--a number that will certainly increase as people with HIV live longer
      thanks to effective antiretroviral therapy. For older women, sorting out the
      interplay between HIV, aging, and the side effects of medications can be very
      difficult. Many health problems are exacerbated by smoking, obesity, and poor
      health behaviors that can lead to an increased risk of illness or death. This
      article addresses two common health risks in aging women with HIV: heart disease
      and osteoporosis.

PMID- 16610118
TI  - Dual HIV infection.
AB  - A number of individuals infected with more than one strain of HIV have been
      identified over the past few years. Should people already diagnosed with HIV be
      concerned? Given the limited number of cases seen so far, the risk of multiple
      infections (also called dual infection) appears to be quite low. And there are
      many more pressing health concerns facing people living with HIV/AIDS.
      Nevertheless, two trends are worth noting: dual infection seems more likely to
      happen under certain conditions, and it is associated with faster progression to
      AIDS-related events. This article describes current evidence and theories behind
      this emerging phenomenon.

PMID- 16610119
TI  - A guide to clinical trials. Part II: interpreting medical research.
AB  - Part I of this two-part article, which appeared in the Summer 2005 issue of BETA,
      provided an overview of the clinical trial process. Part II covers features of
      clinical trials and interpretation of study results. Clinical trials provide the
      foundation for evidence-based medicine, or medical decision-making guided by data
      from formal research. Medical professionals keep up with the latest information
      by reading peer-reviewed medical journals and attending conferences. Likewise,
      HIV positive people can keep abreast of the state of the art by following the
      medical literature and community publications like BETA. Trials offer important
      information about a therapy's benefits and risks in a population, but they cannot
      predict how well a given treatment will work for a specific person. Healthcare
      providers, therefore, must still rely heavily on clinical experience, intuition,
      and a careful evaluation of the various factors unique to each individual case-
      the practice of medicine remains an art as well as a science.

PMID- 16610120
TI  - ICAAC round-up. Experimental drug update and other conference news.

PMID- 16610121
TI  - Hepatitis B: the other hepatitis virus. Prevention, diagnosis and treatment of
      HIV/HBV co-infection--part one of two.

PMID- 16610122
TI  - The politics of HIV. Prevention and politics.

PMID- 16610123
TI  - One-on-one: Mardge Cohen. A Chicago doctor making a difference in Rwanda.
      Interview by Jeff Berry.

PMID- 16610124
TI  - Saving Africa. Baylor College and Secure the Future program pave the way on the
      continent.

PMID- 16610125
TI  - A special girl, two special doctors. Saving lives, saving the world.

PMID- 16610126
TI  - Early intervention for metabolic complications of HIV. A healthy lifestyle and
      treatment early on may prevent complications down the road.

PMID- 16610127
TI  - [DC conductivity of DNA solution].
AB  - DNA with different length was solved into ultra-pure water, the conducing
      behavior of the suspension was investigated at varied temperature and DNA
      concentration. The electrical conductivity of the samples increased with the
      increment of temperature and concentration of the solution. In terms of the
      length, the short-strand DNA (less than 50bp) showed a better conducting
      capability than the long-strand DNA(more than 1000bp). The electrical
      conductivity of short-strand DNA arrives at 1.08 x 10(-3) S/cm at room
      temperature. The conductance of the two DNA samples became similar at high
      temperature as well as their uptrend when DNA samples were heated.

PMID- 16610128
TI  - Effects of fish farm loading on sea grass Posidonia oceanica at Vrgada Island
      (Central Adriatic): a nitrogen stable isotope study.
AB  - Analyses of nitrogen stable isotopes in the marine sea grass Posidonia oceanica
      were used to investigate the influence of fish farming on the coastal ecosystem
      of Vrgada Island in the Murter Sea, Central Adriatic. The results show a
      statistically significant 15N enrichment (up to 4.7 per thousand at p < 0.005) in
      P. oceanica leaf and shoot tissues from fish cage sites with respect to the
      unaffected offshore reference site of Lumbarda Reef Flat (Kornati Islands). Heavy
      nitrogen enrichment was also detected in other benthic organisms analysed during
      this study and is attributed to the absorption and assimilation of 15N-enriched
      fish farm derived nitrogen waste.

PMID- 16610129
TI  - The Human Genome Project: an examination of its challenge to the technological
      imperative.
AB  - Increasingly scientists and governmental policymakers find themselves leaving
      their laboratories and office cubicles to share information and decision making
      with the general public. Contributing in large part to the development of science
      communication via the mass media has been the Human Genome Project (HGP).
      Examining the development of the HGP in the United States beginning with the
      early 1970s helps to establish why and how the general public has become a major
      player in science policy in the United States during the past quarter century,
      especially in regard to the ethical, legal, and social implications of research
      on human genetics. Calling into question the technological imperative--the idea
      that all things scientific must be pursued without question--the general public
      came to realize that exerting control over research funding is the key to
      participating in the scientific process.

PMID- 16610130
TI  - From sequencing to annotating: extending the metaphor of the book of life from
      genetics to genomics.
AB  - The article discusses how the metaphor of the Book of Life was extended over time
      to cover the life cycle of the Human Genome Project from genetics to genomics. In
      particular, the focus is on the role of extendable metaphors in the debate on the
      Human Genome Project in three European newspapers, popular scientific journals
      and scientific and scholarly articles from 1990 to 2002. In these different
      domains of use, various parts of the metaphor were highlighted. The metaphor of
      Book of Life was mainly used to justify the continuation of the gene research
      from gene sequencing to comparative genomics. Readily extendable metaphors, such
      as the Book of Life, function as useful communicative tools both over time and
      across domains of use.

PMID- 16610131
TI  - Untying the Gordian knot of creation: metaphors for the Human Genome Project in
      Greek newspapers.
AB  - This article studies the metaphorical expressions used by newspapers to present
      the near completion of the Human Genome Project (HGP) to the Greek public in the
      year 2000. The analysis, based on cognitive metaphor theory, deals with the most
      frequent or captivating metaphors used to refer to the human genome, which give
      rise to both conventional and novel expressions. The majority of creative
      metaphorical expressions participate in the discourse of hope and promise
      propagated by the Greek media in an attempt to present the HGP and its outcome in
      a favorable light. Instances of the competing discourse of fear and danger are
      much rarer but can also be found in creative metaphorical expressions. Metaphors
      pertaining to the Greek culture or to ancient Greek mythology tend to carry a
      special rhetorical force. However, it will be shown that the Greek press
      strategically used most of the metaphors that circulated globally at the time,
      not only culture specific ones.

PMID- 16610132
TI  - A sequence of 'factishes': the media-metaphorical knowledge dynamics structuring
      the German press coverage of the human genome.
AB  - This article deals with the cultural framing of the near sequencing of the human
      genome and its impact on the media coverage in Germany. It investigates in
      particular the way in which the weekly journal Die Zeit and the daily newspaper
      Frankfurter Rundschau reported this media event and its aftermath between June
      2000 and June 2001. Both newspapers are quality papers that played an essential
      role in framing the human genome debate--alongside the Frankfurter Allgemeine
      Zeitung--which became the most prominent genomic forum. The decoding of the human
      genome prompted a huge controversy concerning the ethics of human engineering,
      research on stem cells and Preimplantation Genetic Diagnosis. The main aim of
      this article is to show how this controversy was structured by metaphor. The
      media coverage of the genome generated DNA-factishes--a neologism designating the
      ambivalence of something as fact (fait) and as a fetish (fetiche)--that mostly
      propagated images of a new DNA-scienticism or biological determinism. Mediated by
      cultural experiences, the human genome became a highly artificial and social
      construct of a 'NatureCulture'.

PMID- 16610133
TI  - The wave phenomena in smooth muscle syncytia.
AB  - Based on the concept of a functional unit, a mathematical model of a segment of
      the gut is developed. The model comprises real anatomical, histomorphological,
      physiological, and pharmacological information on the function of the organ.
      Numerical investigation into the dynamics of the electromechanical wave
      phenomenon reveals the fundamental principles of wave initiation, formation, and
      propagation along electrically anisotropic longitudinal and isotropic circular
      smooth muscle syncytia. A pattern of self-sustained electrical activity with the
      formation of spiral waves is discovered in the longitudinal syncytia and is
      attributed to the change in conductivity in the syncytia as a result of
      mechanical deformation of smooth muscle fibers. The model adequately predicts the
      effects of pharmacological interventions on the dynamics of myoelectrical
      activity. Although no direct experimental comparison to the theoretical findings
      is possible at this stage, the proposed mathematical model provides new insight
      onto the basics of physiological processes--slow wave activity, electromechanical
      conjugation, etc.--and a clinical entity--gastrointestinal dysrhythmias.

PMID- 16610134
TI  - Identification and characterization of Bombyx mori eIF5A gene through
      bioinformatics approaches.
AB  - As the genome of B. mori is available in GenBank and the EST database of B. mori
      is expanding, identification of novel genes of B. mori was conceivable by data
      mining techniques and bioinformatics tools. In this study, we used the in silico
      cloning method to identify eukaryotic initiation factor 5A (eIF5A) gene in B.
      mori. With the hypusine formation, eIF5A is involved in the regulation of cell
      proliferation and apoptosis. Using the computer program MEGA3, we conducted a
      search for homologs of eIF5A among many eukaryotic species and confirmed that the
      eIF5A was conserved in all organisms investigated. This gene has been registered
      in GenBank under the accession number DQ104412.

PMID- 16610135
TI  - Comparative analysis of methodologies for the detection of horizontally
      transferred genes: a reassessment of first-order Markov models.
AB  - With the advent of larger genome databases detection of horizontal gene transfer
      events has been transformed into an increasingly important issue. Here we present
      a simple theoretical analysis based on the in silico artificial addition of known
      foreign genes from different prokaryotic groups into the genome of Escherichia
      coli K12 MG1655. Using this dataset as a control, we have tested the efficiency
      of four methodologies commonly employed to detect HTG (Horizontally transferred
      genes), which are based on (a) the codon adaptation index, codon usage, and GC
      percentage (CAI/GC); (b) a distributional profile (DP) approach made by a gene
      search in the closely related phylogenetic genomes; (c) a Bayesian model (BM);
      and (d) a first-order Markov model (MM). All methods exhibit limitations
      although, as shown here, the BM and the MM are better approximations. Moreover,
      the MM has demonstrated a more accurate rate of detections when genes from
      closely related organisms are evaluated. The application of the MM to detect
      recently transferred genes in the genomes of E. coli strains K12 MG1655, O157
      EDL933, and Salmonella typhimurium, shows that these organisms have undergone a
      rather significant amount of HTG, most of which appear to be pseudogenes. Few of
      these sequences that have undergone HGT appear to have well defined functions and
      may be involved in the organism's adaptation.

PMID- 16610136
TI  - Science fiction/science fact: medical genetics in news stories.
AB  - News media coverage of biotechnology issues offers a rich source of fictional
      portrayals, with stories drawing strongly on popular imagery and metaphors in
      descriptions of the powers and dangers of biotechnology. This article examines
      how science fiction metaphors, imagery and motifs surface in British newspaper
      (broadsheet and tabloid) coverage of medical genetic issues, focusing on press
      reporting of two recent highly publicised news media events; namely, the Hashmi
      and Whitaker families' plights to use stem cells from a 'perfectly matched
      sibling' for the treatment of their diseased children. It is concerned in
      particular with the extent to which journalists' use of certain literary devices
      encourages preferred formulations of medical genetics, and thereby potentially
      shapes public deliberation about scientific developments and their consequences
      for society. Understanding how science fiction sustains science fact, and vice
      versa, and how the former is portrayed in news media, it is argued, would thus
      seem to be crucial in the effort to understand why people respond so strongly to
      biotechnologies, and what they imagine their consequences to be.

PMID- 16610137
TI  - Identification of candidate genes at quantitative trait loci on chicken
      chromosome Z using orthologous comparison of chicken, mouse, and human genomes.
AB  - This study was undertaken to identify novel candidate genes at quantitative trait
      loci (QTL) on chicken chromosome Z (GGAZ) by comparing orthologous regions of
      chicken, human and mouse genomes. Primer sequences from marker flanking QTL
      positions (https://acedb.asg.wur.nl/) were obtained from www.iastate.edu/chickmap
      and blasted against the chicken genome (www.ensembl.org) using BLASTN. The best
      matches were those with the highest score, lowest E-values and highest percent
      identity. Orthologous regions in mice and humans, together with genes located on
      or around those loci were identified using the Ensembl website. Forty-six chicken
      genes, 91 mouse genes and 60 human genes associated with QTL on GGAZ were
      identified in the current study. Among the most promising candidate genes for egg
      production and egg shell quality are annexin A1 (ANXA1), osteoclast stimulating
      factor (OSF), thrombospondin-4 (THBS4), programmed cell death proteins (PDCD),
      follistatin (FST), growth hormone receptor (GHR), interferon (IFN) alpha and
      beta. The chicken IFN alpha and beta were located on GGAZ around position
      13,000,000 bp on the draft chicken sequence map. The neuronal nicotinic
      acetylcholine receptor (nAChR) is located at a QTL region for abdominal fat (GGAZ
      25483091 bp). Nicotine is an agonist at the nAChRs and has been shown to decrease
      lipolysis and triglyceride uptake, thereby reducing net storage in adipose
      tissue. Therefore, the nAchRs could be used as therapeutic targets for regulating
      feed intake and obesity. This study has identified 197 putative candidate genes
      in probable QTL regions of chicken chromosome Z.

PMID- 16610138
TI  - DoD: Database of Databases--updated molecular biology databases.
AB  - Database of Databases (DoD) is a collection of molecular biology databases
      extracted from Nucleic Acids Research, 2005 Database issue. DoD is constructed
      using javascript and html code. The 14 categories of 719 databases are provided
      with a search option, keyword help and database description linked to respective
      pages. Keyword help lists the search strings used to perform an individual search
      against categorized databases. Database description provides brief information
      about the database with a link to full-text article and main web page. DoD is
      available online and can be accessed at http://www.progenebio.in/DoD/DoD.htm.

PMID- 16610139
TI  - u-Genome: a database on genome design in unicellular genomes.
AB  - Unicellular eukaryotes were among the first ones to be selected for complete
      genome sequencing because of the small size of their genomes and their
      interactions with humans and a broad range of animals and plants. Currently, ten
      completely sequenced unicellular genome sequences have been publicly released and
      as the number of available unicellular genomes increases, comparative genomics
      analysis within this group of organisms becomes more and more instructive.
      However, such an analysis is difficult to carry out without a suitable platform
      gathering not only the original annotations but also relevant information
      available in public databases or obtained by applying common bioinformatics
      methods. With the aim of solving these difficulties, we have developed a web
      accessible database named u-Genome, the unicellular genome design database. The
      database is unique in featuring three datasets namely (1) orthologous proteins
      (2) paralogous proteins and (3) statistical distributions on exons, introns,
      intergenic DNA and correlations between them. A tool, Uniview, designed to
      visualize the gene structures for individual genes in the genome is also
      integrated. This database is of importance in understanding unicellular genome
      design and architecture and evolution related studies. The database is available
      through a web interface at http://sege.ntu.edu.sg/wester/ugenome.

PMID- 16610140
TI  - Are there morally problematic reasons for having children?

PMID- 16610141
TI  - Just care: rationing in a public health crisis.

PMID- 16610142
TI  - Medicaid in 2006: a trip down the yellow brick road.
AB  - This issue brief explores the continuing evolution of the Medicaid program on
      several fronts. It discusses the benefits and cost-sharing flexibility that is
      included in the Deficit Reduction Act of 2005 (DRA) and examines the implications
      of these provisions for states, beneficiaries, and providers. The paper also
      explores recent trends in section 1115 waiver development and considers the use
      of waivers as a vehicle for restructuring Medicaid financing systems and for
      testing completely new approaches to health care delivery. The role of section
      1115 waivers in the context of the DRA and as a mechanism for continued state
      innovation is also discussed.

PMID- 16610143
TI  - Bibliography. Current world literature. Urolithiasis.

PMID- 16610144
TI  - Protective mask in quick rehabilitation after rhinoplasty on professional
      sportsmen: protective mask after rhinoplasty.

PMID- 16610145
TI  - Hashmi and Whitaker: an unjustifiable and misguided distinction?

PMID- 16610146
TI  - The regulation of gene therapy research in competent adult patients, today and
      tomorrow: implications of EU Directive 2001/20/EC.

PMID- 16610147
TI  - Informed consent to medical treatment: the common law and New Zealand's Code of
      Patient's Rights.

PMID- 16610148
TI  - Posthumous reproduction.

PMID- 16610150
TI  - The use of prebirth parentage orders in surrogacy proceedings.

PMID- 16610149
TI  - The "embryo" wars: at the epicenter of science, law, religion, and politics.

PMID- 16610151
TI  - Medicare program; Medicare graduate medical education affiliation provisions for
      teaching hospitals in certain emergency situations. Interim final rule with
      comment period.
AB  - This interim final rule with comment period will modify the current Graduate
      Medical Education (GME) regulations as they apply to Medicare GME affiliations to
      provide for greater flexibility during times of disaster. Specifically, this rule
      will implement the emergency Medicare GME affiliated group provisions that will
      address issues that may be faced by certain teaching hospitals in the event that
      residents who would otherwise have trained at a hospital in an emergency area (as
      that term is defined in section 1135(g) of the Social Security Act (the Act)) are
      relocated to alternate training sites.

PMID- 16610152
TI  - Cryopreserved embryos: a response to "forced parenthood" and the role of intent.

PMID- 16610153
TI  - Criminal conception: behind the white coat.

PMID- 16610154
TI  - Regulation of assisted reproductive technologies in the United States.

PMID- 16610155
TI  - Pandora's progeny: ethical issues in assisted human reproduction.

PMID- 16610156
TI  - Sense-making, grief, and the experience of violent loss: toward a mediational
      model.
AB  - Bereavement following violent loss by accident, homicide or suicide increases the
      risk for complications in grieving. This is the first study to examine a
      constructivist model of grief that proposes that sense-making, or the capacity to
      construct an understanding of the loss experience, mediates the association
      between violent death and complicated grief symptomatology. An ethnically diverse
      sample of 1,056 recently bereaved college students completed the Inventory of
      Complicated Grief (ICG) and questions assessing the degree of sense-making and
      the circumstances surrounding their losses. Consistent with this study's primary
      hypothesis, sense-making emerged as an explanatory mechanism for the association
      between violent loss and complications in grieving. Specifically, the results
      revealed that sense-making explained this relation, even when the element of
      sudden bereavement was shared by all of the participants. Overall, this study
      provides initial support for a model of grief in which failure to find meaning in
      a loss is conceptualized as a crucial pathway to complicated grief
      symptomatology.

PMID- 16610157
TI  - Internet-based cognitive-behavioral therapy for complicated grief: a randomized
      controlled trial.
AB  - The present study investigates the efficacy of an Internet-based cognitive
      behavioral therapy program for bereaved people suffering complicated grief. The
      program combines established methods of psychotherapy with new technology-
      therapists and patients communicated exclusively by e-mail. Bereaved individuals
      diagnosed with complicated grief (n = 55) were randomly assigned to either the
      treatment group or a waiting list control condition. The 5-week intervention
      consisted of three modules: (1) exposure to bereavement cues; (2) cognitive
      reappraisal; and (3) integration and restoration. The Impact of Event Scale
      (IES), a failure to adapt scale, and the depression and anxiety subscales of the
      Brief Symptom Inventory (BSI) were used to assess treatment outcomes.
      Participants in the treatment group (n = 26) improved significantly relative to
      participants in the waiting condition on symptoms of intrusion, avoidance,
      maladaptive behavior, and general psychopathology, and showed a large treatment
      effect. Follow-up results show that this improvement was maintained after 3
      months.

PMID- 16610158
TI  - Thoughts of death and suicidal ideation in nonpsychiatric human immunodeficiency
      virus seropositive individuals.
AB  - The present study examines the prevalence of death thoughts and suicidality in
      HIV infection. Subjects (n = 246) were examined for psychiatric morbidity and
      suicidality. Compared to high risk HIV seronegatives, HIV seropositives (HIV +)
      had significantly increased frequency and severity of both suicidal ideation and
      death thoughts. Two-thirds of seropositives had suicidal ideation at some point;
      half of the seropositives reported suicide plans and one quarter suicide
      attempts; and third of seropositives reported current suicidal ideation. Suicidal
      ideation did not increase with advancing disease. The high prevalence of suicidal
      ideation suggests inclusion of its assessment in HIV treatment regardless of
      stage.

PMID- 16610159
TI  - Smart and suicidal? The social ecology of intelligence and suicide in Austria.
AB  - According to de Catanzaro's (1981) evolutionary theory of human suicide, a
      threshold intelligence is necessary for suicidality. A corollary deducible from
      this assertion is that intelligence and suicide mortality should be positively
      related. The present study tested de Catanzaro's corollary within a country.
      Using district-level IQ data of the entire non-institutionalized Austrian male
      year-of-birth cohort of 1969 who survived up to compulsory military conscription,
      including IQ testing in 1987 (n = 55474), the subsequent (1987-2001) district
      level cohort loss due to suicide mortality was investigated. Across 99 Austrian
      districts, the regional IQ was weakly but statistically significantly, positively
      related to the regional standardized suicide rate as well as to the regional
      percentage of mortality due to suicide in this very cohort, when these relations
      were controlled for likely confounders (male divorce and unemployment rates and
      male net income), but not statistically reliable without these controls. It is
      argued that the most parsimonious interpretation of these aggregate-level
      findings remains that intelligence level and suicide mortality are positively
      related.

PMID- 16610160
TI  - Influenza revisited.

PMID- 16610161
TI  - [The Einstein's year].

PMID- 16610162
TI  - Osteoporosis in liver cirrhosis--overview.
AB  - Osteoporosis can occur as a result of liver cirrhosis. The pathogenesis of
      reduced bone mineral density in liver cirrhosis is multifactorial. It can be
      caused by alterations in calcium and vitamin D homeostasis, as well as
      nutritional and dietary factors. Dual-energy X-ray absorptiometry (DXA) has
      become the gold standard in assessing bone mineral density in patients with liver
      cirrhosis. In such cases, patients can be treated with calcium and vitamin D
      supplements, bisphosphonates and hormonal replacement therapy (HRT).

PMID- 16610163
TI  - [Effects of psychological stress on health].
AB  - The stress is defined as a self perceived negative or unpleasant impact. Distress
      is reserved for the experience of specific symptoms such as anxiety or
      depression. The term stressor covers some environmental circumstances directly or
      indirectly affecting the individual. As Selye has suggested, we must remember
      that stress is the great equalizer of biological activities. If we use the same
      parts of our bodies or minds over and over again, nature has only stress with
      which to face us out of the routine. As a consequence, unhealthy levels of stress
      lead to a variety of disorders and illness.

PMID- 16610164
TI  - [Treatment of hepatocellular carcinoma: hepatic resection and liver
      transplantation].
AB  - Hepatocellular carcinoma (HCC) has become a major public health problem since
      it's incidence is continuously growing and a high mortality is related. The
      programs have permitted the early detection of HCC in order to apply the curative
      available treatment strategies. Hepatic resection is still the elective method
      for non-cirrhotic patients with HCC. Tumoral postresection recurrence is frequent
      (60-70%) and it is represented by intrahepatic metastasis or by the development
      of a new tumor. Milan criteria for liver transplantation need a new extension;
      despite improvement in surgical technique and immunosuppression, there are still
      many unknown aspects regarding the selection of the patients and the time needed
      to find the donor for transplantation.

PMID- 16610165
TI  - [The correlation between NT-proBNP plasma levels and heart failure syndrome].
AB  - proBNP represents the precursor of the brain natriuretic peptide (BNP) and is
      released by the cardio-myocytes as a result of the myocardial stretch. It is
      fractioned into two components, BNP and NT-proBNP. We use more often the
      determination of NT-proBNP levels in laboratory tests because of its prolonged
      biological half-time (60-120 minutes, much longer than the BNP half-life). AIM:
      To determine a link between the plasmatic levels of NT-proBNP and heart failure
      syndrome (HFS). MATERIAL AND METHOD: We studied 40 patients admitted in the
      Internal Medicine Clinic of the Western University "Vasile Goldis" Arad, during a
      two years period (2004-2005). Every patient had a clinical examination, an
      echocardiography and the determination of NT-proBNP levels. For the determination
      of the BNP plasmatic levels we used a special kit Elecsys proBNP, which is now
      largely available. The NT-proBNP levels were correlated with the HFS diagnosis
      (the presence of dyspnea and the ejection fraction). RESULTS: In 29 patients the
      NT-proBNP levels were above the upper limit of 125 pg/ml, 86% of them being
      clinically diagnosed with HFS. 11 patients had BNP levels in the normal values
      range and 4 of them were clinically diagnosed with HFS. Correlating the NT-proBNP
      plasma levels and NYHA class of HF we could establish some guidelines regarding
      the critical BNP values upon which the diagnostic of HFS is almost certain. The
      minimum level of BNP at which a patient was diagnosed with HF was 89.9 pg/ml.
      Levels above 125 pg/ml predicts o risk six times higher for HFS. DISCUSSIONS: The
      BNP plasma values may be modified in hepatic or renal failure, which can cause
      false high levels of hormone. These situation should be considered possible error
      sources of diagnosis if the HFS is evaluated only by the means of NT-proBNP
      plasma levels. CONCLUSIONS: The dosage of plasma levels of NT-proBNP is useful
      into patients with suspected HFS, if the other methods of diagnosis are not
      reliable. There is a link between the NT-proBNP plasma levels and the NYHA HFS
      class. However only the dosage of BNP is not sufficient for a correct diagnosis
      of HFS.

PMID- 16610166
TI  - [Treatment with hydroxymethylglutaryl coenzyme-A-reductase inhibitors in elderly
      patients: is it necessary?].
AB  - OBJECTIVE: To study the benefit of the therapy with hydroxymethylglutaryl
      coenzyme A reductase inhibitors (simvastatin) associated with diet in treating
      dyslipidemia in elderly patients, considering that they are more exposed to
      sudden death, myocardial infarction and stroke. Efficient and long-term serum
      cholesterol concentration lowering has beneficial effects on the risk for
      coronary heart disease as well as on other major cardiovascular risk factors such
      as hypertension and diabetes. METHODS: A retrospective study of 84 patients aged
      > or = 65 years, admitted in the last 6 months in Medical Clinic IV, was
      conducted. Admission criteria in the study were: age > or = 65 years old and high
      serum levels of cholesterol, triglycerides and LDL-C/HDL-C ratio. The patient
      population was divided into two groups: Group I of 40 patients treated for
      dyslipidemia only with diet and Group II with 44 patients in which was associated
      treatment with hydroxymethylglutaryl coenzyme A reductase inhibitors, 10 mg/day.
      The patients were controlled when admitted in the study and then at 3 and 6 weeks
      afterwards. RESULTS: Serum cholesterol and triglycerides concentration lowering
      was modest in Group I at 3 and 6 weeks, maybe because we registered a
      progressively lowered compliance of patients to hypocholesterolemic diet. In
      Group II the results were much better as we obtained significant serum
      cholesterol and triglycerides levels lowering after 3 weeks of treatment, and in
      32 cases (72%) we had a normal lipid profile after 6 weeks of treatment. The
      other 12 patients (28%) abandoned treatment after 4 weeks of therapy because of
      financial reasons. There were no side effects during the treatment with
      hydroxymethylglutaryl coenzyme A reductase inhibitors. CONCLUSIONS: The therapy
      with hydroxymethylglutaryl coenzyme A reductase inhibitors associated to
      hypocholesterolemic diet controlled efficiently dyslipidemia in elderly patients.
      Diet alone could not control cholesterol and triglycerides levels, mainly because
      of lack of adherence of the patients to the diet. Based on the fact that
      dyslipidemia is a major, independent cardiovascular risk factor, we consider that
      therapy with hydroxymethylglutaryl coenzyme-A-reductase inhibitors is beneficial
      in elderly patients because of their efficacity, minimal side effects and
      protection against sudden death, myocardial infarction and stroke.

PMID- 16610167
TI  - [Remission of primary vesicoureteral reflux in children with medical management].
AB  - We studied the spontaneous resolution rate in children with primary
      vesicoureteral reflux (VUR) and the interference of some specific factors. We
      reviewed the records of 110 children (14 days - 16 years) admitted in the 4th
      Pediatric Clinic Iasi with primary VUR, between 1994 - 2003, which had exclusive
      medical management and minimum one follow-up cystogram. We used Kaplan-Meier
      curves to analyze the resolution rate of VUR during the follow-up in relation
      with initial grade, age at diagnosis, gender, recurrent urinary tract infections
      (UTIs) and the presence of renal scarring. The remission rate for all the cases
      was 70%, with differences based on the reflux grade: 100% for grade I and 45% for
      grade IV. The cases diagnosed during infancy recovered faster than those
      diagnosed after this period. The presence of renal scarring and breakthrough UTIs
      increased the remission time. In conclusion the majority of patients with VUR
      resolved during medical management, the remission rate being influenced by the
      reflux grade, presence of renal scarring and breakthrough UTIs.

PMID- 16610168
TI  - [Prematurity--risk factor for morbidity in infants].
AB  - The premature child from the anatomo-physiological deficiencies represents one of
      the most important medical problems. In this context we present the results of an
      retrospective study on 2 lots of infants followed for one year in the Infant Care
      Clinic of Iasi. The first lot was formed by infants with a normal weight at birth
      and the second one by premature infants. At this two lots we study the age of
      admission in Clinic, the care period, the nutritional status, the total number of
      diseases, the type of affections. We study the most frequent affections of
      infants such as: respiratory, digestive, otic, cutaneo-mucous. The total number
      of diseases was 61 for the first lot and 153 for the second lot. From the
      affections the most frequently were respiratory diseases 60% for the first lot
      and 104% for the second lot (p < 0.01). The digestive affections were presented
      at 47.5% of first lot of children and 92% for the second one (p < 0.001); the
      otic affections 25% for the first lot and 50% for the second one (p < 0.05);
      cutaneo-mucous affection were represented by 20% from the first lot and 60% for
      the second one (p < 0.001). CONCLUSIONS: The prematurity continued to represent
      one of the most important risk factors of morbidity to infant, for that to those
      children we must to grant a special medical care.

PMID- 16610169
TI  - [MRI in acute pancreatitis].
AB  - 26 patients with clinical and biological suspicion of acute pancreatitis were
      examined by MRI. The general indications for pancreatic MRI were: suboptimal or
      equivocal CT or ultrasonography findings (e.g. focal pancreatic enlargement with
      no mass discernable on CT or US), contraindications to iodinated contrast
      administration (e.g. contrast allergy history and renal failure). Using fast
      scanning techniques most of them with breath holding and fat saturation MRI was
      able to depict the lesions involved (e.g. the presence and distribution of
      necrotic areas and fluid collections, the existence of subsequent chronic
      pancreatic changes) which are consistent with CT findings. MRCP demonstrated
      etiology, like cholelithiasis.

PMID- 16610170
TI  - [Subacute bacterial endocarditis due to Pasteurella pneumotropica. Case Report].
AB  - Endocarditis due to Pasteurella pneumotropica are very rarely described. We
      report a new case of bacterial endocarditis in a 43 years-old patient with mitral
      stenosis. The patient was admitted to the hospital for lethargy, malaise and
      hemiparesis. On physical examination, a new systolic murmur was found.
      Transthoracic echocardiography revealed a vegetation on the mitral valve. Three
      blood culture sets were drawn and after 24 hours of incubation, the last two sets
      yielded Pasteurella pneumotropica and cell wall deficient forms (L-forms). The
      patient was successfully treated with gentamicin and ceftriaxone and underwent
      mitral valve replacement.

PMID- 16610171
TI  - [Differentiated thyroid cancer--peculiar morphological and clinical forms].
AB  - The most common clinical presentation of differentiated thyroid cancer (DTC),
      consisting of papillary and follicular adenocarcinoma (with their histological
      variants), is the solitary thyroid nodule. A review of the literature is
      performed in order to describe particular forms of DTC, in terms of incidence,
      diagnosis and treatment: occult carcinoma, carcinoma on aberrant thyroid tissue,
      "functional" thyroid carcinoma and familial non-medullary carcinoma. A particular
      interest is shown to the coexistence of malignancy with benign thyroid diseases,
      such as goiter, hyperthyroidism and Hashimoto's thyroiditis, as well as
      parathyroid adenoma. In conclusion, the authors emphasize that the association of
      carcinoma with benign thyroid conditions is not rare and it substantiate an
      aggressive approach in regard to diagnosis and treatment, increasing the
      indication for surgery and, moreover, for total thyroidectomy.

PMID- 16610172
TI  - [Current strategy in colorectal cancer screening].
AB  - Screening programs should begin by classifying the individual patient's level of
      risk based on personal, family, and medical history, which will determine the
      appropriate approach for each subject. The individual's risk status determines
      when screening should be initiated and what tests and frequency are appropriate.
      To achieve these aims, care systems should establish standards and operating
      procedures. This review focuses on colorectal cancer screening methodology
      highlighting the latest available strategies.

PMID- 16610173
TI  - Mechanical ventilation in vascular coma patients.
AB  - Vascular coma is one of the leading complications in patients suffering
      cerebrovascular accidents and it is therefore entirely appropriate that we should
      consider what critical care has to offer in this devastating disease process.
      Vascular coma patients need ventilatory assistance; Intubation and mechanical
      ventilation represent a life saving intervention. As critical care is subjected
      to progressive changes, careful definition of the role of mechanical ventilation,
      its types, and the ability of such a form of life sustaining support to affect
      patient outcome in multi-sided directions is mandatory.

PMID- 16610174
TI  - [Vulvar intraepithelial neoplasia. An issue of gynecologic interest].
AB  - The term vulvar intraepithelial neoplasia is used to designate squamous
      proliferative lesions characterized by disorders of cell maturation and nuclear
      abnormalities at various levels in the vulvar epithelium. Due to the fact that 40
      50% of the patients are asymptomatic, the standard of diagnosis remains
      visualization and biopsy of all suspect vulvar lesions. The risk of VIN evolving
      into an invasive carcinoma is not accurately known but the data from literature
      suggests that 20-30% of these patients will consecutively develop an invasive
      squamous cell carcinoma of the vulva. Choosing the best therapeutic approach for
      these patients is challenging because of the extent of the lesions and,
      frequently, their multifocal nature. Increasing incidence among younger women
      justify a more conservative approach, the aim of the treatment remains however
      the prevention of progression to invasive cancer.

PMID- 16610175
TI  - [Liver resection for hepatocellular carcinoma in cirrhotic patients].
AB  - The incidence of hepatocellular carcinoma (HCC) in cirrhotic patients is
      increasing. Despite advances in imaging and laboratory screening which allow
      earlier diagnosis, the surgeon is all too often confronted with an HCC of
      advanced stage or arising in the setting of severe cirrhosis. Hepatic resection
      is still considered the treatment of choice for hepatocellular carcinoma in
      patients with liver cirrhosis. From 1998 to 2005, 6 patients (5 males, 1 female,
      age 52-70 years, mean age 64.1 years) with HCC associated severe, but well
      compensated liver cirrhosis (Child A-- 4 patients, Child B--2 patients) underwent
      9 hepatic resection in our department. Mean tumor size was 56 mm (range 23-86
      mm). Two of these lesions were in the left liver and four in the right lobe.
      Doppler ultrasonography was performed in all cases and CT in 3 cases to confirm
      the extension of the lesions. Laparoscopy was performed in 3 patients under CO2
      pneumoperitoneum. The Pringle maneuver was not used. The transection of the liver
      parenchyma was obtained by the use of Ligasure and harmonic scalpel. Nine hepatic
      resections were performed: 7 segmentectomy and 2 non-anatomical resections. The
      resection margin was 1 cm. The mean operative time was 90 minutes (range 60-120).
      Mean blood loss was 250 ml and 2 patients required blood transfusion. One patient
      died on the tenth postoperative day from a severe respiratory distress syndrome
      and hepatic failure. Major morbidities occurred in three patients who developed
      moderate postoperative ascites, which resolved successfully with conservative
      treatment in two patients. Limited liver resection in cirrhotic patients with HCC
      is feasible with a low complication rate when careful selection criteria are
      followed (tumor size smaller than 8 cm, Child-Pugh A class and the good general
      conditions of the patients). Other medical and interventional treatments
      (chemoembolization, chemotherapy) can only slow the progress of HCC.

PMID- 16610176
TI  - [Comparative experimental study of left colonic anastomoses in intestinal
      obstruction; the value of anastomoses protection with free peritoneal graft].
AB  - The paper describes the concept of peritoneal graft used to reinforce the colo
      colic anastomoses made in emergency conditions of left colic obstruction,
      experimentally induced by surgical ligature, on Wistar rats. The comparative
      study was done on 24 rats, divided in 3 groups: group A with colic anastomoses
      protected with peritoneal graft, group B with one-layer colic anastomoses and
      group C with two-layer colic anastomoses. After 8 days, 7 rats survived in group
      A, 2 rats in group B and 3 rats in group C. All surviving rats in groups B and C
      presented anastomotic leak with local peritonitis, while in group A the
      anastomosis were healed. For group A, bursting strength of the anastomosis was
      measured and the mean value found was 63.64 cmH2O. It was proved the importance
      of protecting the colic anastomosis with supplementary layers, which increase the
      mechanical resistance and also prevents minor spillage of the colic content
      during the first postoperative days.

PMID- 16610177
TI  - [Comparative electronmicroscopic research on normal palmar aponeurosis and
      adulterated palmar aponeurosis in Dupuytren disease].
AB  - This article represents a comparative research between the normal palmar
      aponeurosis seen with the electron microscope and adulterated palmar aponeurosis
      in Dupuytren disease. For that reason, we harvested normal palmar aponeurosis
      from 5 patients hospitalised in emergency in our department with different
      posttraumatic hand lesions, and adulterated palmar aponeurosis from 15 patients
      with Dupuytren disease. The samples were prepared to obtain sections visualised
      with the electron microscope. Comparative research of these sections lead to the
      conclusion that in the normal palmar aponeurosis the fibroblast is visualised in
      its resting functional form (fibrocytes), and in the adulterated palmar
      aponeurosis in Dupuytren disease the fibroblast is visualised in its active,
      secretory, form. In Dupuytren disease we found an increased, anarchic, collagen
      production, clinically demonstrated by nodules and fibrous strips. This paper is
      just a preliminary stage of a research looking for alternative, noninvasive,
      therapeutical methods in Dupuytren disease (ex. : effects of electromagnetic
      field made by millimeter waves on the adulterated palmar aponeurosis cell
      structure).

PMID- 16610178
TI  - Laparoscopy versus laparotomy for pelvic and lumbar-aortic lymphadenectomy. A 11
      year experience.
AB  - This study is a retrospective comparison of laparoscopy and laparotomy
      lymphadenectomy (pelvic and lumbar-aortic) in cervical cancer stage IA1 and more,
      in a gynaecological service in Lyon, France. MATERIAL AND METHODS: During 11
      years, there were 126 cases of cervical cancer patients in which lymphadenectomy
      was performed, either by laparoscopy or laparotomy. We analysed if there were
      significant differences regarding the 2 accesses in terms of stage, tumour size,
      surgical interventions associated, number of lymph nodes extracted, and outcome.
      RESULTS: Regarding the stage of our cases, 3 of them were IB1, IB2 and IIB; the
      more advanced the stage, the fewer lymphadenectomies were performed by
      laparoscopy. As for the tumour size, the smaller tumour was statistical
      significantly associated with pelvic laparoscopic lymphadenectomy (p = 0.01)
      while the tumours larger than 4 cm mean lumbar-aortic lymphadenectomy by
      laparotomy (p = 0.006). Regarding the associated surgical interventions, the
      laparoscopic lymphadenectomies were associated to low-stage operations:
      conisation/trachelectomy, vaginal or abdominal simple hysterectomy, or extra
      fascial hysterectomy (type 1 or 2). There was no significant difference between
      laparoscopy and laparotomy ways regarding the number of lymph nodes extracted
      (median 13.5 vs 11, p = 0.45 for pelvic nodes, and 8 vs 4 for lomb-aortic nodes,
      p = 0.43, for laparoscopy vs laparotomy). CONCLUSION: Laparoscopic
      lymphadenectomy is as effective as the laparotomy procedures, and the training of
      young gynaecologic oncologists should not ignore laparoscopy as an alternative
      technique for nodes sampling.

PMID- 16610179
TI  - [Peritoneal suture vs. non-suture at caesarean section].
AB  - To assess intraoperative, early and late postoperative morbidity followings non
      closure of parietal and visceral peritoneum during caesarean section as compared
      to usual peritonization. Two groups of 40 pregnant women each were randomized to
      either closure (n = 40) or non closure (n = 40). Statistical analysis compared
      intraoperative and postoperative outcome between the two groups. RESULTS: There
      was significant reduction in operating and anesthesia time, febrile morbidity,
      return of bowel function and period of hospitalization among the non closure
      group. Peritoneal adhesions and upward displacement of bladder were more
      frequently noted during a subsequent caesarean in the closure group. Non closure
      of the peritoneum during caesarean section is a shorter, simpler, cost effective
      procedure associated with lesser febrile morbidity and hospitalization, early
      return of bowel function, reduced frequency of the postoperative adhesions and
      upward displacement of bladder.

PMID- 16610180
TI  - [The use of hysteroscopy in the diagnostic on perimenopausal metrorrhagia. A
      study of 35 cases].
AB  - We have retrospectively evaluated the role of hysteroscopy for the diagnostic of
      the peri-menopausal metrorrhagia. METHODS: The cases included represented
      patients of more than 45 years, with persistent bleeding, from 2 gynecological
      hospitals (one public and one private), during one year, that were submitted to
      hysteroscopy for clarifying the diagnostic. The hysteroscopic endometrium
      descriptions were categorized as: atrophy, normal, simple or suspect hypertrophy,
      polyp, and adenocarcinoma, and they were compared to the pathological exam
      results. RESULTS: The descriptions were distributed among the categories: atrophy
      (8 cases), simple hypertrophy (17), suspect hypertrophy (3), polypoid (5),
      endometrial cancer (2) or normal (4). The correlation to pathological results was
      good, with only 14% of hysteroscopic underestimation of lesions. The sensitivity
      according to type of pathology, was 50 to 100%, specificity between 84% - 100%.
      CONCLUSION: Hysteroscopy is better than "blind" curettage in clarifying
      perimenopausal hemorrhagic endometrial pathology.

PMID- 16610181
TI  - [Metachronous primary cancers of the colon and stomach].
AB  - We report herein a case of 69 years old woman who, in the course of 11 years,
      developed two cancers: carcinoma of the colon fistulization in duodenum and
      adenocarcinoma of the stomach. No polyposis has been found. This patient
      successfully underwent a right hemicolectomy with pancreaticoduodenectomy
      (Traverso-Longmire procedure). A decade later, she suffered a total gastrectomy
      with distal pancreatectomy for gastric adenocarcinoma. The patient made an
      uneventful postoperative recovery. Although patients with primary multiple
      cancers are not common, it is nonetheless important for clinicians to consider
      the possibility of metachronous cancers in patients who were treated for a
      primary malignant tumor.

PMID- 16610182
TI  - [Stress fracture of the internal sesamoid bone of the first metatarsophalangeal
      joint. Case report].
AB  - We present the case of a fourty-two year old truck driver without a major trauma
      history who was diagnosed in our unit as having a stress fracture of the first
      metatarsophalangeal joint medial sesamoid bone. Conservative treatment consisting
      of 30 day immobilisation was our treatment choice. The result was very good and
      at six month follow-up the patient had no complains. We have searched for other
      opinions but there is a paucity of published literature on the injuries of the
      lesser toe sesamoids of the foot. The literature review revealed different types
      of treatment such as: conservative treatment, internal fixation of the sesamoid
      fracture (screw fixation), reduction of weight-bearing pressure on the affected
      sesamoid, ice massage or sesamoidectomy. Due to the fact that the different
      conclusions are based on very few cases, it is no possible to conclude about
      optimal treatment.

PMID- 16610183
TI  - [Pregnancy induced hypertension and renin-angiotensin system: how far is the
      truth?].
AB  - This review aims to describe the new trends in designing the model research for
      the study of pregnancy induced hypertension, with a special focus on the renin
      angiotensin system. There are also discussed some clinical implications.

PMID- 16610184
TI  - [Different phenotypes generated by changes in bcl-2 and p53 expression in breast
      cancer].
AB  - We have identified by immunohistochemistry/ immunocytochemistry the expression of
      bcl-2 molecule in 55 primary breast carcinomas and in 30 corresponding axillary
      lymph nodes metastases, together with a set of molecules known as prognostic
      factors: estrogen receptors, progesterone receptors, and p53 protein. Our results
      demonstrated a significant correlation (p < 0.05) between bcl-2 and hormonal
      receptors expression in tumors, but not in axillary metastases (p < 0.1), a
      significant inverse correlation between bcl-2 and p53 expression in primary
      tumors (p < 0.02), but a significant direct correlation in axillary metastases (p
      < 0.02). The bcl-2+/p53- phenotype, associated with normal breast epithelium, is
      present in 79.17% primary tumors, but only in 15.38% axillary lymph nodes
      metastases. A larger number of lymph nodes metastases expressed a bcl-2+/ p53+
      more aggressive phenotype compared with primary tumors (58.82% versus 48.39%).
      This shows that changes in the expression of bcl-2, p53, estrogen and
      progesterone receptors can lead to an increased cellular aggressiveness and thus
      to an increased tumoral invasive and metastasizing potential.

PMID- 16610185
TI  - [High values of soluble cytokeratin 18 in breast carcinomas may have different
      meanings].
AB  - We have investigated the cellular and serum CK18 in 26 non-treated primary ductal
      invasive breast carcinomas. The soluble CK18 (TPS) was detected by
      chemiluminescent assay, and the cellular CK18 and PCNA expression by
      immunocytochemistry. Flow-cytometry was used to estimate the amount of DNA in
      malignant cells. There was a significant correlation between soluble CK18 and the
      pre-menopausal status (p < 0.05), characterized in our group by a PCNA estimated
      low proliferation index. We have also found a significant correlation between
      soluble CK18 and the DNA index (p < 0.01). The intracellular CK18 has correlated
      with the PCNA expression (p < 0.05), while no correlation could be found between
      cellular and serum CK18. The values of soluble CK18 may offer information about
      the treatment-induced cell death, if monitored, while isolated measurements
      should be interpreted cautiously. Elevated levels of serum CK18 in non-treated
      carcinomas may rather reflect a high tumor turn-over or perhaps a more intensive
      tumor cell killing.

PMID- 16610186
TI  - [Checking a model of cardiac segmentation of the left half of the heart].
AB  - The present work is aimed to study the distribution of the coronary arteries to
      the left ventricle; 120 fresh and prepared human hearts harvested from healthy
      individuals of both sexes aged 4 to 78 have been used. The denomination of the
      cardiac segments is the one used by Liberato, Didio & Rodrigues in 1983. Starting
      from this model, we sought for sustaining or invalidating arguments. We used
      special dissection techniques, radiographs of radioopaque substances injected
      hearts, and corroded after plastic substances injection organs. Each ventricular
      segment in the left ventricle is supplied by an arterial branch (called
      "segmental") of the coronary arteries (left coronary artery in most of cases).
      The anterior interventricular branch segment (I SV or SVIA) is the area of the
      heart supplied by the arterial branch with the same name, originating in the left
      coronary artery. Depending on its length, we found a small segment (the branch
      did not pass over the apex of the heart, thus supplying the sternocostal surface
      of the heart only) in 39 cases (32.5%), and a big segment (the artery ended on
      the diaphragmatic surface of the heart, in the posterior interventricular groove)
      in 81 cases (67.5%). The lateral branch segment (II SV or SVL) includes in most
      of cases (78%) a part of the pulmonary wall of he left ventricle, up to the apex
      (Liberato et al. found a percent of 66). In the rest of cases (22%) it
      additionally includes a part of the diaphragmatic wall of the left ventricle. The
      left marginal branch segment (III SV or SVM) is a big one when it includes parts
      of the pulmonary and diaphragmatic walls of the left ventricle and part of the
      diaphragmatic wall of the right ventricle; it is middle-sized when it includes
      parts of the left and diaphragmatic walls of the left ventricle; it is considered
      small when it extends over parts of the left and diaphragmatic walls of the left
      ventricle adjacent to the pulmonary surface (36%, 40% and 24% of cases,
      respectively). The posterior ventricular branch segment (IV SV or SVP) includes:
      a small part of the diaphragmatic wall of the left ventricle close to the
      pulmonary surface--52 cases (43.3%); the superior half of the diaphragmatic wall
      of the left ventricle up to the posterior interventricular septum--19% of cases;
      the superior third of the left ventricle, up to the septum--20% of cases; the
      superior part of the diaphragmatic wall of both ventricles and the superior part
      of the septum--13.6% of cases. The segments are separated by intersegmental
      planes whose position depends of the degree of development of each cardiac
      segment. No significant differences were observed in what concerns the extension
      of the cardiac segments and the position of intersegmental planes in relation to
      sex. The segments can be totally independent or slightly dependent to the blood
      supply of the neighbouring segments.

PMID- 16610187
TI  - [New methods in cancer research--tissue microarray].
AB  - Cancer research advances imperiously requested for a new reliable method for
      biomarker tissue localization study, with standardized experimental conditions,
      reproducible, fast and at low-prices. Tissue Microarrays technique is the most
      important discovery in histopathology techniques in the last decade. It mainly
      consists in bringing and precisely organizing in a single paraffin block of
      hundreds of micro-cylinders from different blocks. Sections from this new block
      may be processed using almost all analyses (immunohistochemistry, in situ
      hybridization). The clear sightedness of those who developed this technique is
      proved by its rapid acceptance and integration in basic research, prognostic
      factors oncology and drugs discovery, reflected in hundreds of publications.

PMID- 16610188
TI  - [New trends in contraception].
AB  - Since the beginning of the world, humans are trying to find methods to allow the
      control of their fertility. Up to the present, more than a hundred methods of
      contraception were developed, most of them being derivatives from the first
      hormonal used methods. The reality of the modern world has imposed the necessity
      of focusing the research in this field in order to develop the "ideal
      contraceptive". There are three main areas of research, with already encouraging
      results: various combinations of hormonal and barrier methods, the contraceptive
      vaccines, and the systemic methods for men. This article presents a synthesis of
      the latest contraceptive technologies available on the market, and the main areas
      of research in this field, separated by gender.

PMID- 16610189
TI  - [Current issues regarding organic food].
AB  - Destruction and pollution of soil and ground water resources is probably the most
      important ecological problem facing the next generation. Checkable standards
      which certify healthy food products are required by the regulation on organic
      farming of the EU and should also be applied for conventional food production.
      Ecological food contains at least 95% of ingredients from an organic farming
      environment, without interference from pesticides, herbicides, fungicides or
      other chemicals and it is totally different from dietary, functional, enriched,
      fortified, probiotic food. Ecological food is tastier and contains more essential
      amino-acids, vitamin C, and micro-nutriments than usual food. Two major effects
      generated by choosing ecological food are the environmental protection and human'
      health improvement. Buying an ecological product represents the effect of a
      certain attitude. Children's nutrition starts with the most genuine ecological
      product: breast milk. Every parent should give to his child healthy and tasty
      food, for proper development. Decreasing artificial chemicals in the diet and the
      environment represents the first step to a healthier life.

PMID- 16610190
TI  - [The effects of computer-use on adolescents].
AB  - Computers continue to play a vital role in today's generation. The need for
      information about the effects of computers on their users also increases. The
      purpose of this study is to investigate how children and adolescents use a
      computer and to explore the beneficial and harmful effects of computer use on
      children's mental and physical health. The studied group of samples comprised 69
      subjects, aged between 13 and 18 years, who answered to a questionnaire. The
      parents of the children also answered another questionnaire with the same
      subject. Data have been statistically processed using the program SPSS. The
      results were obtained about computer use and the pathological use was identified.
      Some children spend much time on computers, 4% more than five hours/day. 41% of
      the parents believe that the usage of the computer is favorable to the children's
      mental and physical health and development, 49% of parents believe that the
      computer may be harmful. 1.4% of the children had pathological use of the
      computer.

PMID- 16610191
TI  - [Coronal restoration with all ceramic inlay].
AB  - We present a 29 years old female patient treated with an all ceramic inlay. The
      IPS Empress system has been used to make an optimal, esthetic and morpho
      functional restoration. An inlay restoration is a biological prosthetic solution
      that is indicated as a proper treatment possibility for the young patients. The
      IPS Empress inlays are characterized by a good biomechanical behavior, law
      abrasion rate and perfect chromatic integration.

PMID- 16610192
TI  - [Separation of vitamins by non-conventional techniques. Facilitated pertraction
      of vitamin C].
AB  - Pertraction (permeation through liquid membranes) is one of the new techniques
      applied for separation and advanced purification of bioactive compounds. The
      study on the facilitated pertraction of vitamin C with Amberlite LA-2 underlined
      the significant influences of the pH-gradient between the aqueous phases, carrier
      concentration and mixing intensity. Thus, for reaching the maximum efficiency of
      vitamin C pertraction, the pH-value of the initial aqueous phase below 2, the pH
      value of the final aqueous solution greater than 11 and the Amberlite LA-2
      concentration in solvent layer over 80 g/l are required.

PMID- 16610193
TI  - [Experimental modeling of the blood vessels magnetic embolization].
AB  - The embolization of blood vessels is used on a large scale: the method is applied
      in different diseases, in the ablation of organs, but especially in tumor
      necrosis. The embolization can be also magnetic, if the embolus is obtained
      through the deposit in the vessel of magnetic nano or microparticles in the
      presence of an external magnetic field. The objective of our study was the
      modeling of the magnetic embolization using amorphous magnetic microspheres that
      have strong magnetic properties and are biocompatible. Experimental tests were
      made in order to observe the building of the magnetic embolus inside a thin
      spiral tube and to determine the influence of some parameters on the efficiency
      of occlusions: the dimensions of magnetic microspheres (1-300 mm), the debit of
      the liquid (4.66 - 16.5 ml/min), the viscosity of the carrier liquid (1.007 -
      7.34 cSt), the direction and the intensity of the external magnetic field (340 -
      600 Gs), the shape of the tube and the linear length of the deposit (5 - 50 mm).
      Under pre-established experimental conditions the efficiencies of occlusions were
      between 67% and 100%.

PMID- 16610194
TI  - [Microwaves hyperthermia. Preliminary experimental results].
AB  - AIM: The main aim of this study was to present a way of designing a hyperthermia
      device based on microwaves, which will be used for cancer treatment in
      association with radiotherapy. MATERIAL AND METHODS: A hyperthermia device with
      two parts - the electrical part and the mechanical support--was built. The
      surface temperature distribution was evaluated using a plastic material with
      micro-pockets filled with water. RESULTS: The experimental results were obtained
      by measuring the temperature in each micro-pocket. These values helped to
      evaluate the surface temperature distribution and to delimit the region with
      useful temperature.

PMID- 16610195
TI  - [Experimental evaluation of hip dynamics].
AB  - AIM: The main aim of this study was to build a dynamometric platform in order to
      measure the variation of the reaction force on the ground, a very important
      parameter for evaluating the stability of a patient. MATERIAL AND METHODS: A
      dynamometric platform for experimental determination of ground-side reaction was
      design. Using this platform, a theoretical model of the active forces in the limb
      joints was elaborated. RESULTS: The experimental results of experiments on
      healthy persons and patients with locomotion disabilities were combined with the
      theoretical model to determinate the hip reaction force.

PMID- 16610196
TI  - [Title, abstract and keywords: essential issues in medical bibliographic
      research].
AB  - Medical information, conveyed either by books, journal articles, conference and
      congress papers or posters, represents the product, the result of the medical
      research. Note that the informational cycle can be shown schematically as
      Bibliographic information --> Medical research --> Research results -->
      Bibliographic information. The result of the scientific research (articles,
      posters, etc.) re-enters the informational cycle, as bibliographic information
      for a new medical research. The bibliographic research is still a time, and
      effort consuming activity, despite the explosive growth of information
      technology. It requires specific medical, information technology and
      bibliographic knowledge. AIM: The present work aims to emphasize the importance
      of title, keywords and abstract terms selection, to article writing and
      publication in medical journals, and the proper choice of meta-information in web
      pages. MATERIAL AND METHODS: The bibliographic research was made using two
      databases with English language information about articles from international
      medical journals: MEDLINE (PUBMED) and PROQUEST MEDICAL LIBRARY. The results were
      compared with GOOGLE and YAHOO search. These searching engines are common now in
      all types of Internet users (including researchers, librarians, etc.).
      CONCLUSIONS: It is essential for the researchers to know the article registration
      mechanism in a database and the modalities of bibliographic investigation of
      online databases, so that the title, keyword and abstract terms are selected
      properly. The use of words not related to the subject, in title, keywords or
      abstract, results in ambiguities. The writing and the translation of scientific
      words must also be accurate, mainly when article authors are non-native English
      speakers: e.g., chimiotherapy (sic)--20 articles in Medline, 270 articles in
      Google; morphopathology (sic)-- 78 articles in Medline, and 294 in Google;
      morphopatology (sic)--2 articles in Medline, and 12 articles in Google.

PMID- 16610197
TI  - Latest review shows rise in calls related to nursing practice standards.
AB  - Questions and concerns related to nursing practice standards increased to 28
      percent from 18 percent of all consultations in the latest review of
      consultations by the College and Association of Registered Nurses of Alberta
      (CARNA). Consultations were initiated by phone, e-mail, fax or in person by
      registered nurses (RNs), employers or others who sought assistance with issues
      that directly or indirectly affected the delivery of safe, competent and ethical
      nursing care. Increases were also noted in the categories related to health-care
      reform and scope of practice, showing an increase to 12 percent from seven and to
      17 percent from 15 respectively. These increases were offset by a decrease in
      calls related to legal/ethical issues to six percent of all calls from 22 percent
      in the previous review period.

PMID- 16610198
TI  - Quest for knowledge leads to Sundre.

PMID- 16610199
TI  - [A gap in the welfare. Every other low-income earner skips visits to the dentist-
      a public health problem is to be expected].

PMID- 16610200
TI  - [Laryngomalacia--the most common cause of inspiratory stridor in children.
      Supraglottoplasty dominates as the surgical method].

PMID- 16610201
TI  - [The apoB/apoA-I ratio is better myocardial infarction marker than lipids].

PMID- 16610203
TI  - [Tissue donation--a neglected activity. The crucial task is to create good
      conditions].

PMID- 16610202
TI  - [Measurement of apolipoproteins is better than routinely measured traditional
      lipids].

PMID- 16610204
TI  - [Orwell's "1984" in Swedish health care?].

PMID- 16610205
TI  - [Increasing documentation for anthroposophic medicine].

PMID- 16610206
TI  - [Incomprehensibly shallow discussion about "customer directed care"].

PMID- 16610207
TI  - [A poor-man's physician's fight for homeless men in Stockholm].

PMID- 16610208
TI  - Pyrazolopyranopyrimidines as a class of anti-inflammatory agents.
AB  - Pyrazolopyranopyrimidines 6a-c and 8a-c were prepared from the reaction of
      compounds 4a-c or 7a-c with methylamine or ammonium hydroxide solutions.
      Treatment of compounds 6a-c or 8a-c with 2-chloroethyl methyl ether afforded
      their corresponding acyclonucleosides 9a-c or 10a-c, respectively, as a new class
      of acyclonucleosides. All prepared compounds were tested as anti-inflammatory
      agents and some of them revealed moderate to potent anti-inflammatory activity.

PMID- 16610209
TI  - Seasonal variation and analgesic properties of different parts from Curcuma
      zedoaria Roscoe (Zingiberaceae) grown in Brazil.
AB  - This work describes the seasonal variation of curcumenol (1) and dihydrocurdione
      (2), two active terpenoids from different parts (roots, mother rhizome and rugous
      rhizome) of Curcuma zedoaria grown in Brazil. The analysis was carried out by
      high resolution gas chromatography, using external standards for determination.
      The results showed that both terpenoids are present in all the parts studied.
      However, C. zedoaria exhibited about three times more terpenoids in the mother
      rhizome in autumn than in other parts and seasons studied. The antinociceptive
      activity of the dichloromethane extracts from different parts and collected in
      different seasons was studied using the acetic acid-induced abdominal
      constriction model in mice. The extracts obtained from mother rhizome collected
      in autumn and winter at doses of 10 mg/kg body weight, i.p., caused considerable
      antinociceptive activity inhibiting 91.1 and 93.4% of the abdominal
      constrictions, respectively, whereas compounds 1 and 2 caused inhibitions of 64.0
      and 46.0%, respectively. These results confirm that both compounds contribute to
      explain the antinociceptive effect of the plant but suggest that other compounds
      are also acting as analgesics.

PMID- 16610210
TI  - In vitro cytotoxicity of norditerpenoid alkaloids.
AB  - Forty-three norditerpenoid alkaloids isolated from Aconitum, Delphinium and
      Consolida species have been evaluated for their cytotoxic effects on the tumor
      cell lines CT26 (murine colon adenocarcinoma), SW480 (human colon
      adenocarcinoma), HeLa (human cervical adenocarcinoma), SkMel25 (human melanoma)
      and SkMel28 (human malignant melanoma) with several multidrug resistance
      mechanisms and the non-tumor cell line CHO (Chinese hamster ovary cells). Neoline
      (5), 8-O-methylcolumbianine (6), 1,14-diacetylcardiopetaline (9), 18-O
      demethylpubescenine (13), 14-deacetylpubescenine (14), pubescenine (15), 14
      deacetylajadine (25), lycoctonine (26), browniine (28), delphatine (29),
      dehydrotakaosamine (34), and ajadelphinine (37) exhibited selective cytotoxicity
      to cancerous versus non-cancerous cells. Some of these compounds had an
      irreversible effect on SW480 (5, 15, 25, 26, and 34), HeLa (15, 34, and 37) and
      SkMel25 (15 and 34) cell lines. In order to gain insights into the mechanism of
      irreversible cytotoxic action of these compounds we compared the cell viability
      by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
      (MTT) and the acid phosphatase (AP) methods. Our results suggest that the effects
      of these compounds could be related to the inhibition of ATP production.

PMID- 16610211
TI  - Isolation and HPLC quantitative analysis of antioxidant flavonoids from
      Alternanthera tenella Colla.
AB  - Phytochemical analysis of the antioxidant ethanolic extract of Alternanthera
      tenella Colla led to the isolation of six flavonoids, acacetin 8-C-[alpha-L
      rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranoside] (1), 2"-O-alpha-L
      rhamnopyranosyl-vitexin (2), 2"-O-beta-D-glucopyranosyl-vitexin (3), vitexin (4),
      quercetin (5) and kaempferol (6). All the structures were established by ESI-MS
      and NMR spectroscopic methods. Antioxidant capacity of extract, fractions and
      isolated compounds was determined using the oxygen radical absorbance capacity
      (ORAC) assay and extract, fractions and flavonoids isolated showed antioxidant
      activity in vitro. Moreover, the total soluble phenolic contents of the extract
      and fractions were measured using the Folin-Ciocalteau reagent and the
      quantitative analysis of flavone C-glycosides major constituents was performed by
      HPLC.

PMID- 16610212
TI  - Anti-inflammatory and antinociceptive activity of flavonoids isolated from Viscum
      album ssp. album.
AB  - Viscum album L. has been used in the indigenous systems of medicine for treatment
      of headache and some inflammatory diseases. In order to evaluate this
      information, antinociceptive and anti-inflammatory activities of the five
      flavonoids (5,7-dimethoxy naringenin or 4',6'-dimethoxy chalcononaringenin)
      derivatives, isolated from the ethyl acetate fraction of the extract from V.
      album ssp. album, were investigated, namely 5,7-dimethoxy-flavanone-4'-O-beta-D
      glucopyranoside (1), 2'-hydroxy-4',6'-dimethoxy-chalcone-4-O-beta-D
      glucopyranoside (2), 5,7-dimethoxy-flavanone-4'-O-[2"-O-(5"'-O-trans-cinnamoyl)
      beta-D-apiofuranosyl]-beta-D-glucopyranoside (3), 2'-hydroxy-4',6'-dimethoxy
      chalcone-4-O-[2"-O-(5"'-O-trans-cinnamoyl)-beta-Dapiofuranosyl]-beta-D
      glucopyranoside (4), 5,7-dimethoxy-flavanone-4'-O-[beta-D-apiofuranosyl-(1 -->
      2)]-beta-D-glucopyranoside (5). For the antinociceptive activity assessment the p
      benzoquinone-induced writhing test and for the anti-inflammatory activity the
      carrageenan-induced hind paw edema model in mice were used. The ethyl acetate
      fraction in a dose of 250 mg/kg as well as compounds 2 and 5 in a 30 mg/kg dose
      were shown to possess remarkable antinociceptive and anti-inflammatory activities
      per os without inducing any apparent acute toxicity as well as gastric damage.

PMID- 16610213
TI  - Derivatization does not influence antimicrobial and antifungal activities of
      applanoxidic acids and sterols from Ganoderma spp.
AB  - Applanoxidic acids and sterols, isolated from Ganoderma spp., were acetylated
      and/or methylated. The antibacterial activity against Escherichia coli and
      Staphylococcus aureus and the antifungal activity against Candida albicans and
      Trichophyton mentagrophytes of the derivatives were investigated by a
      microdilution method, and compared with those of the natural products. Both
      natural and modified compounds exhibited comparable antibacterial and antifungal
      activities in a range of 1.0 to > 2.0 mg/ml minimal inhibitory concentration.

PMID- 16610214
TI  - Antifungal and antibacterial activities of Araucaria araucana (Mol.) K. Koch
      heartwood lignans.
AB  - Five lignans (secoisolariciresinol, pinoresinol, eudesmin, lariciresinol, and
      lariciresinol-4-methyl ether) were isolated from an MeOH extract from Araucaria
      araucana (Mol.) K. Koch wood for the first time in this species and their
      structures determined with spectroscopic methods. The antimicrobial activities of
      these compounds were determined for the bacteria Citrobacter sp., Bacillus
      subtilis, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, and
      Pseudomonas aeruginosa, and for the white rooting and staining fungi Mucor
      miehei, Paecilomyces variotii, Ceratocystis pilifera, Trametes versicolor, and
      Penicillium notatum, and in addition, the MeOH extract was evaluated against
      Aspergillus niger, Candida albicans, Fusarium moniliforme, F. sporotrichum and
      Trichophyton mentagrophytes. The most sensitive bacteria against pinoresinol were
      the Gram-positive. However, secoisolariciresinol exhibited a significant
      antifungal activity on fungi of white rooting and wood staining and this compound
      completely inhibited the mycelial growth of T. versicolor and C. pilifera at 300
      and 400 microg per disc, respectively, whereas pinoresinol showed a moderate
      inhibitory activity. On the other hand, the MeOH extract had the highest activity
      against rooting and staining and pathogenic fungi as well as T. versicolor,
      Fusarium spp. and Trichophyton mentagrophytes, inhibiting completely the growth
      at 400 microg per disc.

PMID- 16610215
TI  - A new active compound from Centaurea species.
AB  - The extract containing sesquiterpene lactones of Centaurea iberica (Asteraceae)
      isolated was separated and a steroidal compound, which is stigmast-1,5-dien-3beta
      ol, was purified. The chemical structure was established based on spectroscopic
      data (UV, IR, MS, 1H NMR, 13C NMR). Both the extract and the compound showed
      significant antioxidant and antimicrobial activities.

PMID- 16610216
TI  - Determination of usnic acid in some Rhizoplaca species from Middle Anatolia and
      their antimicrobial activities.
AB  - Three species of lichens, Rhizoplaca chrysoleuca (Sm.) Zopf, Rhizoplaca
      melanopthalma (DC.) Leuckert & Poelt and Rhizoplaca peltata Ramonds Leuckert,
      were collected from middle Anatolia, Erciyes Mountain (Kayseri) in Turkey. Their
      usnic acid amounts were determined by HPLC in acetone extracts. In addition,
      antimicrobial activities of these extracts were determined against Escherichia
      coli (ATCC 35218), Enterococcus faecalis (RSKK 508), Proteus mirabilis (Pasteur
      Ens. 235), Staphylococcus aureus, Bacillus subtilis, Bacillus megaterium and
      Pseudomonas aeruginosa. It was shown that, as the usnic acid amount increased,
      the antimicrobial activities increased too. The usnic acid contents of Rhizoplaca
      species varied between 0.19-4.0% dry weight.

PMID- 16610217
TI  - Chemical composition and inhibitory activity of essential oil from decaying
      leaves of Eucalyptus citriodora.
AB  - A study was undertaken to explore the content and composition of volatile oil
      from decaying leaves of lemon-scented eucalypt (Eucalyptus citriodora Hook.) not
      analyzed earlier. GC and GC-MS analysis of the oil (yield 0.6%) revealed the
      monoterpenoid nature with citronellal (52.2%), citronellol (12.3%) and
      isoisopulegol (11.9%) as the major constituents. Overall, 17 components were
      identified that accounted for over 94% of the decaying leaf oil. Surprisingly,
      the decaying leaf oil contained nearly 1.8% of trans-rose oxide, which is
      generally absent in eucalypt essential oil. Decaying leaf oil and its major 2
      components (citronellal and citronellol) inhibited the germination and root
      elongation of two weeds--Cassia occidentalis (broad-leaved) and Echinochloa crus
      galli (grassy weed). Based on the dose-response studies, I50 values were
      determined for decaying leaf oil and the effect was more on germination only of
      broad-leaved weed (C. occidentalis), whereas that of citronellal and citronellol
      were on germination as well as root length of E. crus-galli (grassy weed). Based
      on I50 values it was observed that citronellal was more phytotoxic and
      germination inhibiting in nature, whereas citronellol was a more potent root
      inhibitor, thereby indicating a possible different mode of action. The study
      concludes that decaying leaf oil hold a good commercial value for exploitation as
      weed management agent.

PMID- 16610218
TI  - Molluscicidal activity and new flavonoids from Egyptian Iris germanica L. (var.
      alba).
AB  - The molluscicidal activity of leaf and rhizome extracts of Iris germanica L.
      (var. alba) against Biomphalaria alexandrina snails was evaluated and the rhizome
      extracts were found to be the most potent. Activity-guided fractionation revealed
      that the chloroform extract showed the highest molluscicidal activity (LC90 =
      1.26 mg/l) among the tested extracts of the rhizomes. Fraction B prepared from
      the chloroform extract was the most potent molluscicide (LC90 = 0.96 mg/l) in
      addition, it showed a significant heart rate reduction in the snail after a 6- to
      24-h exposure period. It also displayed a significant level of cercaricidal
      potential in a time-concentration relationship pattern. Chromatographic
      fractionation and purification of fraction B resulted in the isolation of two
      novel compounds: 5,2'-dihydroxy-3-methoxy-6,7-methylenedioxyflavone and 5,7,2'
      trihydroxy-6-methoxyflavanone. Their structures were established by one- and two
      dimensional NMR methods and mass spectrometry.

PMID- 16610219
TI  - Pinostrobin--an anti-leukemic flavonoid from Polygonum lapathifolium L. ssp.
      nodosum (Pers.) Dans.
AB  - AIM OF STUDY: Search for plant compounds possessing anti-leukemic properties.
      RESULTS: We have shown that 5-hydroxy-7-methoxy flavanone (pinostrobin) isolated
      from Polygonum lapathifolium ssp. nodosum quickly penetrates through cytoplasm to
      the cellular nucleus of the cultured cells, and gives intensive apoptotic
      response in stimulating leukemic cells in vitro. The number of apoptotic cells
      increased with the concentration of pinostrobin: 10 nM - 25% and 60%; 100 nM -
      45% and 76%; 1 microm - 70% and 88% for Jurkat and HL60 cell lines, respectively
      CONCLUSION: Pinostrobin may be considered as a good candidate for a leukemia
      chemopreventic agent.

PMID- 16610220
TI  - Herbicidal potential of catechol as an allelochemical.
AB  - Catechol is an allelochemical which belongs to phenolic compounds synthesized in
      plants. Its herbicidal effects on weed species; field poppy (Papaver rhoeas),
      creeping thistle (Cirsium arvense), henbit (Lamium amplexicaule) and wild mustard
      (Sinapis arvensis) were investigated using wheat (Triticum vulgare) and barley
      (Hordeum vulgare) species as control plants. In comparison to 2,4-D (a common
      synthetic herbicide), 13.64 mM of catechol have been found to have a strong
      herbicidal effect, as effective as 2,4-D on field poppy weed by killing it, and a
      suppressive herbicidal effect on the other weeds by inhibiting their growth
      significantly. Concerning all the weeds, in general, elongation of the shoot was
      affected more negatively than that of the root. Fresh weights of the weeds were
      decreased by catechol significantly only in field poppy but not in other weeds.
      The study reveals that catechol is a potent inhibitor of growth of the weeds and
      therefore it can be evaluated as a herbicide for future weed management
      strategies.

PMID- 16610221
TI  - Effects of fifteen rare-earth metals on Ca2+ influx in tobacco cells.
AB  - Effects of naturally existing rare-earth metals (REMs; atomic numbers, 39, 57-60,
      62-71; Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu), added as
      chloride salts, on Ca2+ influx induced by two different stimuli, namely
      hypoosmotic shock and hydrogen peroxide, were examined in a suspension-cultured
      transgenic cell line of BY-2 tobacco cells expressing aequorin, a Ca(2+)
      sensitive luminescent protein in cytosol. Most REM salts used here showed
      inhibitory effect against Ca2+ influx. Especially NdCl3, SmCl3, EuCl3, GdCl3 and
      TbCl3 showed the most robust inhibitory action. In contrast, LuCl3, YbCl3, ErCl3
      and YCl3 were shown to be poor inhibitors of Ca2+ influx. Since REMs tested here
      form a sequential range of ionic radii from 86.1 to 103.2 pm and the optimal
      range of ionic radii required for blocking the flux of Ca2+ was determined for
      each stimulus. The hydrogen peroxide-induced Ca2+ influx was optimally blocked by
      REMs with a broad range of ionic radii (93.8-101 pm) which is slightly smaller
      than or similar to that of Ca2+ (100 pm), while the hypoosmotically induced flux
      of Ca2+ was inhibited optimally by few REMs with a narrower range of relatively
      smaller ionic radii around that of Gd3+ (93.8 pm) a well known inhibitor of
      stretch-activated channels. Possible applications of such series of channel
      blockers in elucidation of plant signal transduction pathways are encouraged.

PMID- 16610222
TI  - Cucurbitane glucosides from Momordica charantia leaves as oviposition deterrents
      to the leafminer, Liriomyza trifolii.
AB  - The American serpentine leaf mining fly, Liriomyza trifolii, whose larva feeds on
      more than 120 plant species is well characterized by its high degree of
      polyphagy. Observations on the oviposition behavior by L. trifolii demonstrated
      that among cucurbitaceous plants, Momordica charantia is rarely attacked by L.
      trifolii. The methanol extract of M. charantia leaves strongly deterred the
      females from ovipositing on kidney bean leaves treated at a concentration of 1 g
      leaf equivalent extract/ml. Analysis of the polar fraction of the methanol
      extract of M. charantia leaves resulted in the isolation of a novel cucurbitane
      glucoside, 7-O-beta-D-glucopyranosyl-3,23-dihydroxycucurbita-5,24-dien-19-al,
      named momordicine IV, along with another known compound, momordicine II.
      Momordicine II and IV deterred oviposition by L. trifolii significantly when
      bioassays were carried out on kidney bean leaves treated at 75.6 and 20.3
      microg/cm2 leaf surface, respectively. There was no synergistic effect on
      oviposition deterrent when the two compounds were combined in their natural
      abundance.

PMID- 16610223
TI  - Production of biosurfactant using different hydrocarbons by Pseudomonas
      aeruginosa EBN-8 mutant.
AB  - The present investigation dealt with the use of previously isolated and studied
      gamma-ray mutant strain Pseudomonas aeruginosa EBN-8 for the production of
      biosurfactant by using different hydrocarbon substrates viz. n-hexadecane,
      paraffin oil and kerosene oil, provided in minimal medium, as the sole carbon and
      energy sources. The batch experiments were conducted in 250 mL Erlenmeyer flasks,
      containing 50 mL minimal salt media supplemented with 1% (w/v) hydrocarbon
      substrate, inoculated by EBN-8 and incubated at 37 degrees C and 100 rpm in an
      orbital shaker. The sampling was done on 24 h basis for 10 d. The surface tension
      of cell-free culture broth decreased from 53 to 29 mN/m after 3 and 4 d of
      incubation when the carbon sources were paraffin oil and n-hexadecane,
      respectively. The largest reduction in interfacial tension from 26 to 0.4 mN/m
      was observed with n-hexadecane, while critical micelle dilution was obtained as
      50 x CMC for paraffin oil as carbon source. When grown on n-hexadecane and
      paraffin oil, the EBN-8 mutant strain gave 4.1 and 6.3 g of the rhamnolipids/L,
      respectively. These surface-active substances subsequently allowed the
      hydrocarbon substrates to disperse readily as emulsion in aqueous phase.

PMID- 16610224
TI  - Lovastatin production by Pleurotus ostreatus: effects of the C:N ratio.
AB  - The types of carbon source and nitrogen source used as well as the C:N ratio in
      the medium influenced lovastatin production by Pleurotus ostreatus. The maximum
      value of the lovastatin yield was obtained in a medium that contained organic
      nitrogen.

PMID- 16610225
TI  - Sucrose metabolism of perennial ryegrass in relation to cold acclimation.
AB  - Sugar metabolism is one of the important factors involved in winter hardiness and
      since the discovery of sucrose biosynthesis, considerable advances have been made
      in understanding its regulation and crucial role. This investigation examined the
      changes in activities of sucrose metabolizing enzymes and sugar content during
      cold hardening of perennial ryegrass (Lolium perenne L.). Changes in acid
      invertase (AI), sucrose synthase (SS) and sucrose phosphate synthase (SPS) along
      with all the three soluble sugars glucose, fructose and sucrose were measured in
      leaves and stem base tissue during cold acclimation. Although fructans were the
      predominant carbohydrate the changes in glucose, fructose and sucrose were
      significant. All the three soluble sugars in both leaf and stem tissues started
      to decrease from the first day and continued up to day 7 and thereafter started
      to increase until day 28. AI in the soluble fraction showed a higher activity
      than that in the cell wall bound fraction. In both the leaf and stem bases
      soluble AI activity increased during the first week and after that it started to
      decrease gradually. On the other hand both the SS and SPS increased gradually
      throughout the acclimation period. Sucrose content was negatively correlated with
      AI and positively correlated with SS and SPS accounting well for the relation
      between the substrate and enzyme activity. These results suggest that AI, SS and
      SPS in ryegrass are regulated by cold acclimation and play an important role in
      sugar accumulation and acquisition of freezing tolerance.

PMID- 16610226
TI  - Simultaneous cultivation of Spirulina platensis and the toxigenic cyanobacteria
      Microcystis aeruginosa.
AB  - Mangueira Lagoon, located in the extreme south of Brazil, has water with
      physicochemical characteristics such as alkaline pH and carbonate levels
      propitious for the growth of the cyanobacterium Spirulina platensis. Previously
      published studies have shown that Mangueira Lagoon water supplemented with small
      quantities of carbon and nitrogen is suitable for S. platensis cultivation and
      can significantly reduce production costs. We studied mixed cultures of Spirulina
      platensis and the toxic cyanobacterium Microcystis aeruginosa using a 2(3)
      factorial design in which the three factors were the initial biomass
      concentration of S. platensis and M. aeruginosa and the type of culture medium
      (100% Zarrouk's medium or 80% Mangueira Lagoon water plus 20% Zarrouk's medium).
      The highest S. platensis maximum specific growth rate (mu(max)) occurred in the
      culture with the highest M. aeruginosa biomass concentration and when undiluted
      culture medium was used (micro(max) = 0.283 d(-1)). The highest M. aeruginosa
      specific death rate (k) was obtained in the presence of S. platensis (k = 0.555
      d(-1)) and was independent of the initial M. aeruginosa biomass concentration and
      culture medium, demonstrating that S. platensis cultures are not susceptible to
      contamination by M. aeruginosa. The culture medium had no significant influence
      (p > 0.05) on S. platensis micro(max) values, indicating that production costs
      could be reduced by using a medium consisting of 80% Mangueira Lagoon water plus
      20% Zarrouk's medium.

PMID- 16610227
TI  - Characterization and subcellular localization of chlorophyllase from Ginkgo
      biloba.
AB  - Chlorophyllase (Chlase) catalyzes the initial step of chlorophyll (Chl)
      degradation, but the physiological significance of this reaction is still
      ambiguous. Common understanding of its role is that Chlase is involved in de
      greening processes such as fruit ripening, leaf senescence, and flowering. But
      there is a possibility that Chlase is also involved in turnover and homeostasis
      of Chls. Among the de-greening processes, autumnal coloration is one of the most
      striking natural phenomena, but the involvement of Chlase during autumnal
      coloration is not clear. Previously, it was shown that Chlase activity and
      expression level of the Chlase gene were not increased during autumnal coloration
      in Ginkgo biloba, indicating that Chlase does not work specially in the de
      greening processes in G. biloba. In this study, we characterized the recombinant
      Chlase and analyzed its subcellular localization to understand the role of the
      cloned Chlase of G. biloba (GbCLH). GbCLH exhibited its highest activity at pH
      7.5, 40 degrees C. Kinetic analysis revealed that GbCLH hydrolyzes pheophytin
      (Pheo) a and Chl a more rapidly than Pheo b and Chl b. Transient expression
      analysis of 40 N-terminus amino acids of GbCLH fused with GFP (green fluorescent
      protein) and subcellular fractionation showed that GbCLH localizes within
      chloroplasts. Together with our previous results, property of GbCLH and its
      location within the chloroplasts suggest that GbCLH plays a role in the turnover
      and homeostasis of Chls in green leaves of G. biloba.

PMID- 16610228
TI  - Identification of Tinospora cordifolia (Willd.) Miers ex Hook F & Thomas using
      RAPD markers.
AB  - Identified germplasm is an important component for efficient and effective
      management of plant genetic resources. Traditionally, plant identification has
      relied on morphological characters like growth habit, floral morphology like
      flower colour and other characteristics of the plant. Studies were undertaken for
      identification and genetic variation within 15 clones of Tinospora cordifolia
      through random amplified polymorphic DNA (RAPD) markers. Analysis was made using
      forty decamer primers. Out of them, 15 primers were selected and used for
      identification and genetic relationships within 15 clones. A total of 138
      distinct DNA fragments ranging from 0.2 to 3.2 kb were amplified using 15
      selected random primers. The genetic similarity was evaluated on the basis of
      presence or absence of bands. The genetic distance was very close within the
      clones. Thus, these RAPD markers have the potential for identification of species
      and characterization of genetic variation within the population. This study will
      be helpful to know the genetic background of the medicinal plants with high
      commercial value, and also provides a major input into conservation biology.

PMID- 16610229
TI  - Identification and genetic variation among Hibiscus species (Malvaceae) using
      RAPD markers.
AB  - Germplasm identification and characterization is an important link between the
      conservation and utilization of plant genetic resources. Traditionally, species
      or cultivars identification has relied on morphological characters like growth
      habit or floral morphology like flower colour and other characteristics of the
      plant. Studies were undertaken for identification and determination of genetic
      variation within the two species of Hibiscus and 16 varieties of Hibiscus rosa
      sinensis L. through random amplified polymorphic (RAPD) markers. Primer screening
      was made by using the DNA of variety "Prolific". Genetic analysis was made by
      using ten selected decamer primers. A total of 79 distinct DNA fragments ranging
      from 0.3 to 2.5 kb were amplified by using ten selected random decamer primers.
      The genetic similarity was evaluated on the basis of presence or absence of
      bands. The cluster analysis indicated that the 16 varieties and two species
      formed one cluster. The first major cluster consisted of three varieties and a
      second major cluster consisted of two species and 13 varieties. The genetic
      distance was very close within the varieties and also among the species. Thus,
      these RAPD markers have the potential for identification of species/varieties and
      characterization of genetic variation within the varieties. This is also helpful
      in Hibiscus breeding programs and provides a major input into conservation
      biology.

PMID- 16610230
TI  - Sterol and lipid composition of three Adriatic Sea sponges.
AB  - The sterol and fatty acid composition of three Adriatic Sea sponges (Geodia
      cydonium and two unidentified Tedania sp.), collected at the same time and same
      place, was established. Twenty-four sterols and forty fatty acids were
      identified. The identical ecological conditions, including the diet, allowed us
      to apply the results obtained for taxonomical conclusions, based on the
      biodiversity of the investigated sponges. On the basis of the sterol composition
      they can be separated into two groups: Tedania and Geodia sponges. The sterol and
      fatty acid composition indicates that the two investigated Tedania samples might
      be different species or subspecies.

PMID- 16610231
TI  - Conserved and non-conserved loci of the glucagon gene in old world ruminating
      ungulates.
AB  - The homology and diversification of genomic sequence encoding glucagon gene among
      native Egyptian buffalos, camel and sheep were tested using cattle as model.
      Oligodeoxynucleotide primers designed from the available GenBank data were used
      for PCR probing of the glucagon gene encoding sequence at different loci. The DNA
      oligomer probes were constructed to flank either the whole gene encoding sequence
      or different intra-gene encoding sequences. The PCR products were visualized
      using agarose gel electrophoresis. All species showed a same size band of prepro
      glucagon when PCR was used to amplify the whole gene encoding sequence. In
      contrary, amplifications of different intra-gene loci failed to give the same
      results. The results indicated variable degrees of diversity among old world
      ruminating ungulates in the glucagon gene encoding sequence. Compared with other
      ruminants, the variation appears predominantly in camel. Surprisingly, the
      similarity in size between both amplification products of whole gene encoding
      sequence and the proposed size of glucagon cDNA definitely excludes the
      possibility of large intervening introns spanning the genomic sequence of the
      glucagon gene in these species. This indicates that, in contrast to other tested
      mammals, the glucagon gene includes an essentially full-length copy of glucagon
      mRNA. The study revealed a possible new aspect of glucagon gene evolution in
      order to correlate its corresponding protein function among different ruminant
      species.

PMID- 16610232
TI  - Nickel(II) affects poly(ADP-ribose) polymerase-mediated DNA repair in normal and
      cancer cells.
AB  - Nickel(II) can be genotoxic, but the mechanism of its genotoxicity is not fully
      understood and the process of DNA repair may be considered as its potential
      target. We studied the effect of nickel chloride on the poly(ADP-ribose)
      polymerase (PARP)-mediated repair of DNA damaged by gamma-radiation and
      idarubicin with the alkaline comet assay in normal and cancer cells. Our results
      indicate that nickel chloride at very low, non-cytotoxic concentration of 1
      microM can affect PARP-mediated DNA repair of lesions evoked by idarubicin and
      gamma-radiation. We also suggest that in the quiescent lymphocytes treated with
      gamma-radiation, nickel(II) could interfere with DNA repair process independent
      of PARP.

PMID- 16610233
TI  - Structure of a new tetranuclear iron(III) complex with an oxo-bridge; factors to
      govern formation and stability of oxo-bridged iron(III) species in the L-subunit
      of ferritin.
AB  - We have investigated the reaction products of several iron(III) compounds with
      hydrogen peroxide, and have found that hydrogen peroxide promotes the formation
      of an oxo-bridged iron(III) species in the presence of methanol (electron donor),
      and carboxyl groups of the ligand systems play a role to give the tetranuclear
      iron(III) compound containing a bent Fe-O-Fe unit (O: oxo oxygen atom). Based on
      the present results and the facts that L-chains of human ferritins lack
      ferroxidase activity, but are richer in carboxyl groups (glutamates) exposed on
      the cavity surface, it seems reasonable to conclude that (i) the hydrogen
      peroxide released in the H-subunit may contribute to the formation of a diferric
      oxo-hydrate in the L-subunit, (ii) the formation of a bent oxo-bridged iron(III)
      species is essentially important in the L-subunit, and (iii) rich carboxyl groups
      in L-subunits contribute to facilitate iron nucleation and mineralization through
      the capture and activation of the peroxide ion, and formation of a stable bent
      oxo-bridged iron(III) species.

PMID- 16610234
TI  - Parathyroid hormone regulates osterix and Runx2 mRNA expression predominantly
      through protein kinase A signaling in osteoblast-like cells.
AB  - Runt-related transcription factor 2 (Runx2) and osterix are osteoblast-specific
      transcription factors essential for the development of osteoblastic cells and
      bone formation. PTH given intermittently has anabolic effects on bone; however,
      the exact role remains to be understood completely. The purpose of this study was
      both to investigate whether PTH regulates Runx2 as well as osterix expression and
      to identify the signaling used. Using RT-PCR, we confirmed that PTH (1-34)
      regulated Runx2 and osterix mRNA expression, in rat osteoblast-like cell line UMR
      106, in a dose- and time-dependent manner. PTH in low concentrations stimulated
      both Runx2 and osterix mRNA expression while that in high concentrations did not.
      Forskolin, an adenylate cyclase activator, also enhanced Runx2 and osterix
      transcription, and the stimulatory effects of PTH and forskolin were blocked by
      the pre-treatment of the cells with H-89, a protein kinase A (PKA) inhibitor. In
      contrast, the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate
      (PMA) had no effect on Runx2 transcription, but induced an increase in osterix
      mRNA level at the concentration of 500 nM at 12 h after treatment. Moreover, pre
      treatment of the cells with calphostin C, a PKC-specific inhibitor, reduced the
      increase in osterix transcripts enhanced by PTH and PMA 12 h after treatment.
      However, these inhibitory effects were not sustained for longer terms. These
      observations demonstrate that PTH stimulates Runx2 and osterix expression in
      vitro, at least in part, at transcriptional level. Induction of Runx2 mRNA is
      mediated through the activation of cAMP/PKA signal transduction. In the case of
      osterix, although the increase in mRNA level is predominantly mediated via
      cAMP/PKA signaling, PKC activation might also be involved in this process.

PMID- 16610235
TI  - Dose dependency of the serum bio/immuno GH ratio in children during
      pharmacological secretion tests.
AB  - Dissociation between GH bioactivity (bio-GH) and GH immunoactivity (immuno-GH) is
      due to the heterogeneity of the molecule: the measurements do not always provide
      reliable information on the bio-GH. We studied the ratio of bio-GH and immuno-GH
      during pharmacological secretion tests in 211 sera to study the concentration
      response curve of the assay (C1), 16 samples of normally growing subjects with
      idiopathic short stature (C2), 13 samples from patients with GH deficiency (GHD1)
      and 6 samples of 3 patients with GHD and normal provocative tests (GHD2). GH
      bioactivity was determined by the Nb2 cell proliferation assay (bio-GH) and
      immuno-GH by a time-resolved immunofluorometric assay (IFMA) (immuno-GH). A non
      linear negative relationship between the serum bio-GH/immuno-GH ratio and serum
      immuno-GH was observed in C1. In log-log plotting representation, two cut-off
      lines were drawn: a vertical cut-off line separating above-below cut-off serum
      peak immuno-GH values in provocative tests, and a diagonal cut-off line
      separating normal-abnormal serum bio-GH/immunoGH ratio; four areas were defined.
      GHD1 had normal ratios, but below cut-off peak immuno-GH responses. P2 and P3 of
      Group GHD2 had abnormal ratios in samples with low serum immuno-GH but only P2
      had autosomal dominant mutation. P1 had the same autosomal dominant isolated GHD
      as P2 but a low normal ratio. Our data underline the importance of relatively low
      serum GH concentrations in mediating GH biological actions. An abnormal serum bio
      GH/immuno-GH ratio might explain certain cases of GHD and might be useful in
      detecting abnormal circulating isoforms of GH in patients with growth failure.

PMID- 16610236
TI  - Ghrelin tissue distribution: comparison between gene and protein expression.
AB  - Ghrelin, the natural ligand of the GH secretagogue (GHS) receptor, was originally
      isolated from the stomach and detected in several tissues, but a systematic study
      of its tissue distribution has not been performed. In the present investigation,
      we evaluated ghrelin gene expression (by RT-PCR technique) and ghrelin protein
      concentration (by enzyme immunoassay technique) in tissues obtained from control
      rats as well as in rats subjected to 48-h fasting. The ghrelin gene was expressed
      in stomach, small intestine, brain, cerebellum, pituitary, heart, pancreas,
      salivary gland, adrenal, ovary and testis, with maximum expression occurring in
      the stomach, while no significant expression was detected by standard RT-PCR in
      liver, lung, kidney and skeletal muscle. Ghrelin protein was detected in stomach,
      small intestine, brain, cerebellum, pituitary, lung, skeletal muscle pancreas,
      salivary gland, adrenal, ovary and testis, at concentrations ranging from 0.05 to
      1.43 ng/mg of homogenate protein (the highest concentration occurred in the lung,
      followed by the brain). Ghrelin was not detectable in the heart, liver and
      kidney. Therefore, gene and protein expression were dissociated. Fasting did not
      produce significant changes in ghrelin gene expression, while the distribution of
      ghrelin between different tissues was significantly modified: protein
      concentration increased in the brain, cerebellum, lung and salivary gland, while
      it decreased in the stomach.

PMID- 16610237
TI  - A new mutation in the growth hormone-releasing hormone receptor gene in two
      Israeli Arab families.
AB  - BACKGROUND: Mutations in the GHRH receptor gene (GHRH-R) are emerging as a common
      cause of familial isolated GH deficiency (IGHD). DESIGN: We searched for GHRH-R
      mutations in 10 patients with IGHD of Israeli-Arab origin, belonging to two
      highly consanguineous families. METHODS: Analysis of the 13 coding exons, the
      intron-exon boundaries, and the proximal promoter of the GHRH-R was performed by
      denaturing gradient gel electrophoresis. Abnormally migrating bands were
      sequenced. The newly found mutation was inserted into GHRH-R cDNA. Wild type and
      mutant receptor were expressed in Chinese hamster ovary (CHO) cells, and the cAMP
      response to GHRH was measured. RESULTS: All patients were homozygous for a novel
      GHRH-R missense mutation in exon 11 that replaces arginine with cysteine (R357C).
      Functional assay demonstrated complete inactivity of the mutant receptor in
      vitro. The prevalence of the mutant allele in the Israeli-Arab population was
      found to be 2%. All the patients had low but detectable GH reserve, proportionate
      short stature, and growth retardation since early childhood, with good growth
      response to GH treatment. Magnetic resonance imaging, performed in 3 patients,
      revealed a normal sized anterior pituitary in one patient evaluated at early
      childhood, and a borderline hypoplastic gland in the 2 patients evaluated at
      puberty. CONCLUSIONS: We describe a novel missense mutation in the GHRH-R. The
      high incidence of the mutant allele in Israeli Arabs suggests that the mutation
      may be a common cause of familial IGHD in this population.

PMID- 16610238
TI  - Interventional bronchoscopy in the treatment of tracheal obstruction secondary to
      advanced thyroid cancer.
AB  - BACKGROUND: Surgery is the choice treatment for symptomatic tracheal obstruction
      due to malignant thyroid disease. Few additional therapeutic alternatives are
      available: radiotherapy (RT), chemotherapy (CT) or radioiodine therapy (1311).
      Only few studies on interventional bronchoscopy (IB) as well as alternative or
      palliative procedures have been reported so far. This study is a retrospective
      report of results of IB performed in patients with severe tracheal obstruction
      due to advanced thyroid cancer. SETTING: Pulmonary and Endocrinology Units of a
      University Hospital. PATIENTS AND INTERVENTIONS: From January 2, 2000 to March 1,
      2004 14 consecutive patients [5 males, mean age: 62.2+/-10.7 (SD) yr] underwent
      IB due to tracheal obstruction for anaplastic (ATC: 7 patients), differentiated
      (DTC: 5), medullary (MTC: 1) and non-epithelial malignant (NEMN: 1) thyroid
      cancer. Eight out of 14 patients had local advanced inoperable disease, 6 had
      local relapse after surgery, 1311 or RT. Ten out of 14 patients suffered from
      severe dyspnea. In 4 patients airway patency was maintained by insertion of a
      stent; in 3 the tracheal lesion was removed by Nd-YAG laser; in 7 both procedures
      were performed. RESULTS: All 10 patients with dyspnea showed an improvement in
      symptoms. Early and late complications were observed in 4 and in 3 patients,
      respectively. All but 4 DTC patients died 11.9+/-14.2 months after the diagnosis
      (4.20+/-5.1 after IB). In 4 DTC patients still alive 90.7+/-59.2 since diagnosis
      and 16.7+/-9.2 months since IB, the airway dilatations allowed further treatments
      like 131-I and/or RT. CONCLUSIONS: Interventional bronchoscopy, including Nd-YAG
      laser and airways stenting are alternatives to surgery in inoperable thyroid
      induced tracheal obstruction. Moreover, airway dilatation improves dyspnea and
      may allow further treatment.

PMID- 16610239
TI  - High prevalence of adrenal suppression during acute illness in hospitalized
      patients receiving megestrol acetate.
AB  - INTRODUCTION: Megestrol acetate (MA) is a progestational agent used for
      palliation of breast and endometrial cancer. The drug promotes weight gain via
      appetite stimulation. This property has led to widespread use in patients with
      wasting illnesses. Increasing numbers of reports suggest glucocorticoid activity.
      OBJECTIVE: Unrecognized adrenal suppression may result from MA use. This is the
      first study to examine the prevalence of adrenal suppression in hospitalized
      patients treated with MA. SUBJECTS AND DESIGN: This is a cross-sectional study of
      hospitalized patients receiving MA compared to control subjects. Morning cortisol
      levels, endocrine signs and symptoms, and duration of MA therapy were evaluated
      in 28 hospitalized medical patients treated with MA, and 21 control patients
      admitted to the same hospital service during the study period. RESULTS: Median
      cortisol levels were significantly lower in patients using MA vs controls (160 vs
      386 nmol/l, p=0.003). Forty-three percent of subjects on MA demonstrated morning
      cortisol levels below the normal range (138-690 nmol/l), compared with 10% of
      controls (p=0.013). Ninety-three percent of subjects taking MA had morning
      cortisol levels below the level that excludes adrenal insufficiency in
      hospitalized patients (497 nmol/l) vs 71% of controls (p=0.06). CONCLUSIONS: MA
      use is associated with significant adrenal suppression in acutely ill
      individuals. This should alert physicians to the possibility of adrenal
      insufficiency and the need to assess for signs or symptoms of adrenal
      insufficiency, and mandates a low threshold for testing adrenal function in
      hospitalized patients taking MA.

PMID- 16610240
TI  - Endogenous testicular D-aspartic acid regulates gonadal aromatase activity in
      boar.
AB  - D-aspartic acid (D-Asp), aromatase enzyme activity and the putative D-Asp
      involvement on aromatase induction have been studied in the testis of mature
      boars. The peroxidase-antiperoxidase and the indirect immunofluorescence methods,
      applied to cryostat and paraffin sections, were used to evaluate D-Asp and
      aromatase distributions. D-Asp level was dosed by an enzymatic method performed
      on boar testis extracts. Biochemical aromatase activity was determined by in
      vitro experiments carried out on testis extracts. D-Asp immunoreactivity was
      found in Leydig cells, and, to a lesser extent, in germ cells. Analogously,
      aromatase immunoreactivity was present in Leydig cells, but absent from
      seminiferous tubule elements. In vitro experiments showed that the addition of D
      Asp to testicular tissue acetone powder induced a significant increase of
      aromatase activity, as assessed by testosterone conversion to 17beta-estradiol.
      Enzyme Km was not affected by D-Asp (about 25 nM in control and D-Asp added
      tests). These findings suggest that D-Asp could be involved in the local
      regulation of aromatase in boar Leydig cells and intervenes in this organ's
      production of estrogens.

PMID- 16610241
TI  - Expression of potassium channel isoforms mRNA in normal human adrenals and
      aldosterone-secreting adenomas.
AB  - Increased aldosterone secretion has been found in a mouse lacking the KCNE1 gene
      which codes for a regulatory protein of the KCNQ1 gene product, forming the
      channel for the outward rectifying delayed K+ current. Abnormalities in proteins
      regulating the K+ fluxes across membranes may be responsible for aldosterone
      secreting adenomas (aldosteronomas) also because K+ channels are involved in cell
      growth. Normal and adenomatous adrenal samples and NCI-H295 cell line were used
      to: a) evaluate KCNE1 and KCNQ1 gene expression, b) sequence the full length
      cDNAs of KCNE1 and both KCNQ1 isoforms. These differently spliced KCNE1 and KCNQ1
      mRNAs were expressed in adrenal tissue. In contrast, KCNQ1 isoform 2 mRNA was not
      expressed in kidney control tissues and NCl-H295 cell line. NCI-H295 cell line
      also had a significantly lower expression of KCNQ1 isoform 1 mRNA than normal
      adrenals and aldosteronomas. We did not find any somatic mutations in the coding
      sequences of both genes. This different expression pattern of KCNQ1 isoforms in
      NCI-H295 cell line with the lack of the mRNA for the dominant-negative KCNQ1
      isoform 2 supports the involvement of voltage-gated K+ channel in cell
      proliferation.

PMID- 16610242
TI  - GH-binding protein is related to bone mineral density in non-obese androgenized
      women.
AB  - GH and IGF system components are important regulators of bone formation and at
      the same time pathogenetic factors in functional hyperandrogenism (FH) in lean
      females. We studied the relationships between bone mineral density (BMD) and
      serum concentrations of GH, GH-related parameters, androgens and estrogen, in 18
      non-obese women of reproductive age with functional hyperandrogenism compared to
      a group of 10 healthy eumenorrheic age- and weight-matched women. In androgenized
      women, a significant positive correlation was found between BMD and GH-binding
      protein (GHBP), whereas BMD did not correlate to GH or other related parameters.
      It is suggested that higher tissue GH receptor responsiveness in non-obese
      androgenized women may contribute to their higher BMD.

PMID- 16610243
TI  - The potential role of increased adrenal volume in the pathophysiology of obesity
      related type 2 diabetes.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role in
      obesity and Type 2 diabetes (DM). The aim of the present study was to determine
      the adrenal volume in obese patients with DM in comparison to obese non-diabetic
      patients. Eleven diabetic obese and 19 non-diabetic obese women were sequentially
      invited to take part in the study. Computed tomography (CT) scan of the abdomen
      was performed to determine adrenal volume, visceral (VF) and sc fat (SCF). Daily
      urinary free cortisol (UFC) was used as a measure of integrated cortisol
      production. In the diabetic patients, hemoglobin A1c was measured as an index of
      metabolic control. Compared to nondiabetic controls, patients with diabetes had a
      significantly higher total adrenal volume (4.29+/-1.50 vs 2.95+/-1.64; p=0.03). A
      highly significant correlation was detected between VF and VF/SCF ratio and total
      adrenal volume in the whole group (r=0.36, p=0.04 and r=0.48, p=0.008,
      respectively). This study, therefore, suggests an association between abdominal
      obesity, enlarged adrenals and Type 2 diabetes. These findings support the
      hypothesis that an increased activity of the HPA axis in obese subjects may be
      involved in the pathogenesis of Type 2 diabetes.

PMID- 16610244
TI  - Cushing's syndrome during pregnancy secondary to adrenal adenoma: metyrapone
      treatment and laparoscopic adrenalectomy.
AB  - Cushing's syndrome during pregnancy is a rare and difficult to diagnose disorder.
      We describe the case of a 30-yr-old woman presenting with symptoms and signs of
      mild hypercortisolism, in which ACTH-independent Cushing's syndrome was
      diagnosed. Urinary cortisol excretion was elevated and circadian rhythm of
      cortisol was absent. ACTH levels were low. In addition, plasma cortisol failed to
      suppress after a high dexamethasone dose. An abdominal computed tomography scan
      confirmed a left adrenal mass. While diagnosis work-up was still in progress, the
      patient became pregnant and wanted to carry her pregnancy to full-term.
      Hypercortisolism was successfully controlled with metyrapone, which was started
      at 8 weeks of gestation. At 16 weeks of gestation, a laparoscopic left
      adrenalectomy was performed. Pathologic examination of the gland showed a benign
      adrenocortical adenoma. The patient developed secondary adrenal insufficiency and
      was discharged on 20 mg hydrocortisone daily dose. At 30 weeks of gestation, the
      patient had a pre-term rupture of membranes and underwent spontaneous vaginal
      delivery. The newborn was a normal virilized male who weighed 1280 g. No apparent
      metyrapone-induced teratogenic effects were observed and there was no clinical or
      biochemical suppression of adrenocortical function. In conclusion, in adrenal
      Cushing's syndrome during pregnancy, medical treatment with metyrapone as soon as
      the diagnosis is made, in combination with laparoscopic surgery during the second
      trimester, are useful in preventing complications secondary to hypercortisolism
      and safe both for the mother and infant.

PMID- 16610245
TI  - Spindle cell metaplasia arising in thyroid adenoma: characterization of its
      pathology and differential diagnosis.
AB  - Spindle cell metaplasia in thyroid adenoma or carcinoma is rare and its
      pathological features are not well characterized. Distinction of this entity from
      medullary or anaplastic carcinoma has an important clinical implication. We
      encountered a case of thyroid follicular adenoma associated with spindle cell
      metaplasia. It showed "tumor in tumor appearance" and neoplastic spindle cells
      were positive for thyroglobulin, thyroid transcription factor-1, vimentin and
      focally chromogranin A and somatostatin (SS). MIB-1 index was <1%. Ultrastructure
      of the spindle cells was reminiscent of follicular cell origin. From the findings
      from our case, spindle cell metaplasia appears to be a benign clinical entity,
      suggestive of multidirectional differentiation of follicular cells.

PMID- 16610246
TI  - Paraadrenal Castleman disease presenting with adrenal hyperandrogenism.
AB  - Castleman disease, or angiofollicular lymph node hyperplasia, is a rare benign
      lymphoproliferative disorder. We report an uncommon case of retroperitoneal
      Castleman syndrome associated with adrenal hyperandrogenism and with interleukin
      6 as the possible link in the pathophysiology of both disturbances. Four years
      after surgical resection of the paraadrenal mass, the patient is free of signs of
      recurrence of Castleman disease and adrenal hyperandrogenism.

PMID- 16610247
TI  - Multi-step approach in a complex case of Cushing's syndrome and medullary thyroid
      carcinoma.
AB  - The diagnosis of Cushing's syndrome (CS) may sometimes be cumbersome. In
      particular, in ACTH-dependent CS it may be difficult to distinguish between the
      presence of an ACTH-secreting pituitary adenoma and ectopic ACTH and/or CRH
      secretion. In such instances, the etiology of CS may remain unknown despite
      extensive diagnostic workout, and the best therapeutic option for each patient
      has to be determined. We report here the case of a 54-yr-old man affected by ACTH
      dependent CS in association with a left adrenal adenoma and medullary thyroid
      carcinoma (MTC). He presented with clinical features and laboratory indexes of
      hypercortisolism associated with elevated levels of calcitonin. Ectopic CS due to
      MTC was reported previously. In our case hypercortisolism persisted after
      surgical treatment of MTC. Thorough diagnostic assessment was performed, in order
      to define the aetiology of CS. He was subjected to basal and dynamic hormonal
      evaluation, including bilateral inferior petrosal sinus sampling. Extensive
      imaging evaluation was also performed. Overall, the laboratory data together with
      the results of radiological procedures suggested that CS might be due to
      inappropriate CRH secretion. However, the source of CRH secretion in this patient
      remained unknown. It was then decided to remove the left adenomatous adrenal
      gland. Cortisol level fell and has remained within the normal range nine months
      after surgery. This case well depicts the complexity of the diagnostic workout,
      which is needed sometimes to correctly diagnose and treat CS, and suggests that
      monolateral adrenalectomy may represent, at least temporarily, a reasonable
      therapeutic option in occult ACTH-dependent hypercortisolism.

PMID- 16610248
TI  - Association of pelvic endometriosis with alopecia universalis, autoimmune
      thyroiditis and multiple sclerosis.
AB  - An adult Caucasian female developed a previously unreported association of pelvic
      endometriosis (PE) with the triad of alopecia universalis (AU), autoimmune
      thyroiditis (AT) and multiple sclerosis (MS). Molecular human leukocyte antigen
      (HLA)-tissue typing of this subject showed the presence of the DR(2) 15 and DR(3)
      17 alleles, which are associated to an increased risk of MS and AT, respectively.
      Clinical onset of AT followed withdrawal of corticosteroid treatment for AU,
      whereas MS become clinically evident after withdrawal from long-term
      estroprogestin therapy for PE. This clinical case is presented to discuss the
      autoimmune origin of PE, its possible association with multiple autoimmune
      disorders as well as the effect of other factors, such as administration and/ or
      discontinuation of specific hormonal regimens, on genetic autoimmunity-prone
      background.

PMID- 16610249
TI  - Diagnosis of adult growth hormone deficiency: still a matter of debate.
AB  - The diagnosis of GH deficiency (GHD) in adults is established by laboratory
      testing in patients with an appropriate clinical history of hypothalamic
      pituitary disease. As the measurement of IGF-I and IGFBP-3 levels as well as the
      spontaneous GH secretion are not considered reliable parameters, the diagnosis of
      GHD in adults may be established by GH provocative tests, provided that a
      reproducible test with clear normative limits is available. The insulin tolerance
      test (ITT) is a reliable diagnostic test in adults, but is contraindicated in
      several clinical conditions which are often observed in adult patients with
      suspected GHD. The other classic GH provocative tests, except the glucagon test,
      have a poor diagnostic utility and should be abandoned. GHRH combined with
      arginine or GH secretagogues represent a potent, safe, reproducible and reliable
      test which should be preferable to the ITT as a first-choice diagnostic test for
      GHD.

PMID- 16610250
TI  - Bactericidal/permeability-increasing protein antineutrophil cytoplasmic
      antibodies (ANCA) and associated diseases: clinical relevance of an emerging ANCA
      target antigen.

PMID- 16610251
TI  - Hospital care for frail, complex elders: more than a matter of appropriateness.

PMID- 16610252
TI  - Juvenile idiopathic arthritis: an update on clinical and therapeutic approaches.
AB  - Juvenile idiopathic arthritis represents a heterogeneous group of autoimmune
      diseases. It arises before 16 years of age and lasts more than 6 months. We can
      distinguish many arthritis sub-types. A serious problem in juvenile idiopathic
      arthritis is skeletal growth retardation, osteopenia and greater risk of
      developing fractures. Juvenile idiopathic arthritis diagnosis is an exclusion
      diagnosis. Many conditions can simulate it. First-choice drugs in juvenile
      idiopathic arthritis treatment are nonsteroidal anti-inflammatory drugs,
      analgesic and antipyretic drugs. The second-choice drugs are "slow-acting"
      antirheumatic drugs, like methotrexate. The use of glucocorticoids is strongly
      influenced by their side effects, in particular the inhibition of statural growth
      and the premature appearance of osteoporosis. Recent findings on the central role
      of tumor necrosis factor-alpha, in particular damage pathogenesis in the course
      of juvenile idiopathic arthritis, have permitted the development of new
      therapeutic strategies (infliximab, etanercept), aimed at blocking this cytokine.

PMID- 16610253
TI  - [Antiphospholipid syndrome and venous thromboembolism: the role of congenital
      thrombophilia].
AB  - The antiphospholipid syndrome is associated with complications of pregnancy or
      venous or arterial thrombosis in the presence of antiphospholipid antibodies.
      Venous thromboembolism is the most common clinical feature. Pathogenetic
      mechanisms underlying the syndrome are not completely understood and several
      hypotheses have been raised. Secondary prophylaxis after venous thromboembolism
      episodes requires oral anticoagulants (prothrombin time-international normalized
      ratio 2-3) for 6 to 12 months. More intensive anticoagulant regimens are
      indicated in case of recurrence. A longer or life-long course of treatment is
      indicated in patients with recurrent or life-threatening events or in the
      presence of high titers of antiphospholipid antibodies. Among risk factors for
      venous thromboembolism, inherited thrombophilia is recently described, such as
      defects of the physiological coagulation inhibitors, genetic mutations of factor
      V and factor II of the coagulation cascade and hyperhomocysteinemia. High levels
      of factor VIII, factor IX and lipoprotein(a) have recently been proposed as new
      risk factors for venous thromboembolism. The coexistence of inherited
      thrombophilia seems to enhance the thrombogenic risk, in particular in the venous
      vascular bed. The new insights into the diagnosis of inherited thrombophilia
      could allow a better evaluation of the thrombotic risk, leading to tailor the
      prophylactic strategy.

PMID- 16610254
TI  - [Depression in patients with cardiovascular disease].
AB  - Cardiovascular disease and depression, which is frequently encountered in
      developed countries, are unexpectedly linked and someway interdependent. Although
      it has been proven that major depression is a risk factor for cardiovascular
      disease, it is also true that cardiovascular disease may often cause depression.
      This article provides epidemiological data regarding this phenomenon and focuses
      on the mechanisms and causes that link these apparently unrelated pathologies.
      The diagnosis of depression and the difficulty in recognizing it as such are
      reviewed and several tests useful for this purpose are presented. Finally, the
      most common antidepressants particularly suitable for cardiac patients are
      examined along with any possible interactions between these drugs and those
      currently used for treatment of cardiovascular disease.

PMID- 16610255
TI  - [Characteristics of patients admitted to a Division of Internal Medicine. Is
      hospital the best setting of care?].
AB  - The aim of this study was to describe the characteristics of institutionalized
      patients, the patterns of admission, hospital stay and discharge and the extent
      of resource utilization before, during and after hospitalization, in an Acute
      Division of Internal Medicine of a university hospital. All adult patients
      admitted to the division were consecutively enrolled during a 3-month study
      period. Patients underwent a multidimensional assessment and data collection
      concerning admission and discharge patterns, resource utilization, and discharge
      diagnosis. Three hundred and eighteen patients, with an average age of 73.8
      years, entered in the study; the rate of patients both affected by severe
      cognitive and functional impairment was high (29.9%); 3-4 comorbidity classes
      were estimated in 70.8% of patients; the most frequent diagnoses at discharge
      were gastrointestinal (major diagnostic category 6), liver and pancreas diseases
      (major diagnostic category 7); despite the high rate of comorbidity and severity
      of illness, the average diagnosis-related groups was low (1.15 +/- 0.59) and also
      the levels of nursing and personal care provided in the hospital were low (21 +/-
      15 and 19 +/- 16, respectively). Median length of stay was 9 days and 3-4
      comorbidity classes significantly prolonged hospitalization (p < 0.01). The main
      critical aspects concerning hospital admissions were the low rates of general
      practitioner requests of admission (26.7%), the high rates of unplanned
      readmissions (17.9%) and inappropriate recovery (12.6%). Concerning discharge,
      only 18.5% of patients had assisted discharges despite the high rates of patients
      with functional impairment; difficulties at discharge were estimated in 15.0% of
      patients. Our data suggest to improve the relation between hospital and primary
      health services in order to assure appropriateness of patient care and optimal
      use of a specialistic division.

PMID- 16610256
TI  - Soft tissue infection caused by Mycobacterium chelonae following a liposculpture
      and lipofilling procedure.
AB  - Skin and soft tissue infections that usually follow minor traumatic events or
      surgical procedures are caused by a wide spectrum of bacteria. We describe a soft
      tissue infection caused by a Mycobacterium chelonae in an immunocompetent patient
      who underwent liposculpture and lipofilling of the gluteal-trochanteric region,
      emphasizing the importance of clinical suspicion and effective treatment of
      infection.

PMID- 16610257
TI  - Severe bleeding in a case of acquired factor VIII inhibitor associated with
      generalized pustular psoriasis.
AB  - Antibodies against factor VIII occur in about 15-35% of hemophilia A patients and
      induce refractoriness to factor VIII substitution. In very rare cases, factor
      VIII inhibitors also develop in association with various autoimmune and chronic
      inflammatory diseases, hematologic malignancies, solid tumors, certain drugs,
      dermatologic conditions, and in puerperium. In the majority of cases, the
      clinical course is characterized by severe hemorrhages. Strategies to treat such
      inhibitors are controversial. We present the case of a patient with generalized
      pustular psoriasis who developed severe bleeding complications due to an acquired
      factor VIII inhibitor, after lymph node and skin biopsy. Initial treatment with
      high doses of human factor VIII concentrate was unsuccessful. Hemorrhage was
      partially controlled by the administration of recombinant activated factor VII.
      Subsequently, the human factor VIII was reinitiated in association with
      immunosuppressive therapy with prednisone. Within 8 weeks this combined modality
      achieved a complete remission of bleeding, a normalization of coagulation
      parameters and a complete disappearance of the inhibitor. Our case illustrates
      that, although the clinical course in patients with acquired factor VIII
      inhibitor is not predictable and the inhibitor may disappear spontaneously,
      combined modality with replacement and immunosuppressive therapy should be
      considered for patients with severe and refractory hemorrhages.

PMID- 16610258
TI  - [Celiac disease in the elderly: a case report].
AB  - Celiac disease is not a negligible cause of malabsorption in the elderly.
      Diarrhea, loss of weight and abdominal discomfort are often absent so that celiac
      disease has indeed a subtle, paucisymptomatic, course in the elderly. More than
      50% of the patients have extraintestinal symptoms; only 10-40% have typical
      complaints pointing to small-intestinal biopsy. Elimination of gluten from diet
      is the cornerstone of the therapy. A 73-year-old woman with hyporexia, loss of
      weight, depression, bowel abnormalities and progressive deterioration of her
      abilities in the instrumental activities of daily living was referred to our
      department. Antigliadin and antiendomysial antibodies were present. A subsequent
      small-intestinal biopsy of the second and third portion of duodenum showed
      subtotal villous atrophy, increase of intra-epithelial lymphocytes as well as
      hyperplastic glands (type III Marsh score). All these pathological findings were
      compatible with celiac disease diagnosis so that a gluten-free diet was then
      initiated.

PMID- 16610260
TI  - Dentists' influence on restoration longevity.

PMID- 16610259
TI  - [Bronchiectasis worsening by p-ANCA (bactericidal/permeability-increasing
      protein) positive vasculitis. A case report and review of the literature].
AB  - A 67-year-old woman was hospitalized with recurrent fever, arthralgia and
      erythema of the arms and legs. She had suffered from bronchiectasis for the
      previous 4 years, and Pseudomonas was persistently detected in her sputum. During
      the course of her illness, she developed distal sensitive and motor
      polyneuropathy. Serum test was positive for myeloperoxidase and
      bactericidal/permeability-increasing protein antineutrophil cytoplasmic
      antibodies. Nerve biopsy showed vasculitis infiltration of the vasa nervorum. She
      started immunoglobulin therapy, and after methylprednisolone and pulse
      cyclophosphamide therapy once monthly for 6 months she showed a good response and
      a reduction in symptoms.

PMID- 16610261
TI  - Autism: the aetiology, management and implications for treatment modalities from
      the dental perspective.
AB  - Autism is defined as a rare and severe psychiatric disorder of childhood. It is
      marked by severe difficulties in communicating, and forming relationships with
      other people, in developing language, repetitive and limited patterns of
      behaviour and obsessive resistance to small changes in familiar surroundings.
      Hence, affected children offer a special challenge to the practising dentist. To
      meet this challenge, it is necessary to understand the condition and how to
      manage its varying presentations in different individuals. The purpose of this
      article is to review the literature on the topic of autism with an emphasis on
      the dental perspective. CLINICAL RELEVANCE: A better understanding of the effects
      of autism on the behaviour of an affected individual provides the dental
      practitioner with the opportunity to deliver oral healthcare in an empathetic and
      appropriate manner.

PMID- 16610262
TI  - Maintenance of osseointegrated implant prostheses.
AB  - Implant-retained prostheses need to be re-evaluated on a regular basis. This
      should include review of the effectiveness of oral hygiene procedures to maintain
      soft tissue health, evaluation of the integrity and function of the prosthetic
      superstructure and comparison of radiographic bone levels at appropriate
      intervals. CLINICAL RELEVANCE: All dental care professionals need to be aware of
      the maintenance care requirements of patients treated with dental implants. With
      the increase in numbers of patients treated there will be greater demands to
      provide this care in general practices.

PMID- 16610263
TI  - Amalgam: dead or alive?
AB  - The use of dental amalgam is on the decline, yet its many advantages, including
      the contrast in colour with the tooth, increase the possibility that the
      patient's dentition will last a lifetime. CLINICAL RELEVANCE: Dental amalgam is
      still a viable restorative material. A recipe for the placing of better amalgam
      restorations along with clinical restorations of 30-year longevity using these
      techniques is presented.

PMID- 16610264
TI  - Limiting factors in orthodontic treatment: 2. The biological limitations of
      orthodontic treatment.
AB  - Owing to a shortage in the orthodontic workforce in the United Kingdom, general
      dental practitioners carry out orthodontic treatment in selected cases.
      Orthodontic treatment may not always be successful due to various factors. Some
      of these limiting factors are related to the practitioner, others to the patients
      and the orthodontic appliances used. These three sets of factors were covered in
      the first part of this article. This second part deals with the biologic
      limitations of orthodontic treatment. CLINICAL RELEVANCE: General dental
      practitioners and novice orthodontic practitioners may get into difficulties by
      embarking upon an orthodontic treatment which may not be feasible due to various
      limitations imposed by the underlying biology. This article provides a brief
      outline of these limitations.

PMID- 16610265
TI  - Sarcoidosis presenting as an isolated facial swelling--an unexpected diagnosis?
AB  - Sarcoidosis is a rare chronic granulomatous disease of unknown aetiology that
      primarily affects individuals between 30 and 50 years of age. It is usually
      characterized by the presence of non-caseating, granulomatous, epithelioid tissue
      at the sites affected with involvement of lymphoid tissue. Sarcoidosis confined
      to lymph nodes, salivary glands and other tissue in the head and neck is uncommon
      and usually indicative of a more generalized systemic process. Within the
      differential diagnosis of isolated masses associated with the head and neck,
      sarcoidosis is indeed rare. We report a case of systemic sarcoidosis presenting
      as a small localized facial swelling. The report illustrates that other symptoms,
      albeit mild, may direct the clinician to a provisional diagnosis of generalized
      sarcoidosis. CLINICAL RELEVANCE: Within the differential diagnosis of isolated
      facial swellings, sarcoidosis is extremely uncommon. However, clinicians should
      consider the diagnosis, especially in the presence of other, albeit mild,
      symptoms.

PMID- 16610267
TI  - No dentist wishes to deregister their child patients.

PMID- 16610266
TI  - Dental care for the neglected mouth of an adolescent with cerebral palsy: a case
      report.
AB  - A case report is presented of the preventive and clinical care of an adolescent
      with a neglected mouth, complicated by the medical history of cerebral palsy.
      CLINICAL RELEVANCE: Knowledge of the treatment which ideally may be offered to
      patients with cerebral palsy may help such patients retain and maintain their
      dentition.

PMID- 16610268
TI  - Case 32. Physical signs for the general dental practitioner. Pernicious anaemia.

PMID- 16610269
TI  - Spatial associations in number-related tasks: A comparison of manual and pedal
      responses.
AB  - Bimanual parity judgments of numerically small (large) digits are faster with the
      left (right) hand (the SNARC effect; Dehaene, Bossini, & Giraux, 1993). According
      to one explanation, this effect is culturally derived and reflects ontogenetic
      influences such as the direction of written language; it might therefore be
      limited to, or at least be larger with, pairs of lateralized effectors which are
      instrumental to the production and comprehension of written language. We report
      two experiments which test for SNARC effects with pedal responses, and compare
      these effects to manual results. Pedal responses yielded highly systematic SNARC
      effects; furthermore, these effects did not differ from manual SNARC effects.
      These results argue against accounts in which the SNARC effect is specific for
      effectors that are habitually associated with the production or comprehension of
      written language.

PMID- 16610270
TI  - Spatial processing and perceptual sequence learning in SRT tasks.
AB  - We investigated the influence of processing relevant spatial information on
      learning a probabilistic sequence of irrelevant locations. Using the SRT design
      of Remillard (2003), we found that spatial perceptual learning occurs with paired
      but not with single targets. The pairs of targets consisted of the same stimuli,
      but in a different order, so that responses could have been based on the left
      right location of an element, relative to the other element of the pair. The
      prerequisite of spatial pairs of targets suggests that spatial processing of
      relevant information plays a crucial role in perceptual location learning. In
      addition, spatial perceptual learning only took place when the target pair was
      presented together with other stimuli, but was absent when the target pair was
      presented in a blank field. Since in the latter case attention is automatically
      captured, this suggests that sequence learning requires endogenous attention.

PMID- 16610271
TI  - Priming of depth-rotated objects depends on attention and part changes.
AB  - Three priming experiments investigated the role of attention and view changes
      when common objects were rotated in depth. Objects were shown in prime-probe
      trial pairs. Experiment 1 extended findings by Stankiewicz, Hummel, and Cooper
      (1998) showing that attended objects primed themselves in the same but not in a
      reflected view, whereas ignored objects only primed themselves in the same view.
      In Experiment 2, depth-rotations produced changes in the visible part structure
      between prime and probe view of an object. Priming after depth-rotation was more
      reduced for attended objects than for ignored objects. Experiment 3 showed that
      other depth rotations that did not change the perceived part structure revealed a
      priming pattern similar to that in Experiment 1, with equivalent reduction in
      priming for attended and ignored objects. These data indicate that recognition of
      attended objects is mediated by a part-based (analytic) representation together
      with a view-based (holistic) representation, whereas ignored images are
      recognized in a strictly view-dependent fashion.

PMID- 16610272
TI  - Selective stopping in task switching: The role of response selection and response
      execution.
AB  - Recently, several studies stressed the role of response selection in cued task
      switching. The present study tried to investigate directly the hypothesis that no
      switch cost can be found when there was no response selection. In two
      experiments, we combined a cued task switching paradigm with the selective
      stopping paradigm. Results of the experiments demonstrated that a switch cost was
      found when participants selected a response, even without response execution.
      Alternatively, when the response was inhibited without the need of response
      selection, no switch cost was found. These results provide direct evidence for
      the distinct role of response selection in cued task switching and suggest that
      response execution is not a necessary factor to obtain a switch cost.

PMID- 16610273
TI  - Further evidence that the SNARC effect is processed along a dual-route
      architecture: Evidence from the lateralized readiness potential.
AB  - In a binary response setting, it has been frequently observed that small numbers
      are reacted to faster with the left hand and large numbers with the right hand
      (i. e., the SNARC-effect) which reflects the spatial left-right orientation of
      the mental number line (Dehaene, Bossini, & Giraux, 1993). In line with the work
      of Keus and Schwarz (in press), we investigated the locus of the conflict in the
      SNARC effect in a parity judgment task with the Arabic numerals 1, 2, 8, or 9.
      Differences between compatible (left-hand response to 1 or 2 and right-hand
      response to 8 and 9) and incompatible SNARC conditions (left-hand response to 8
      or 9 and right-hand response to 1 or 2) were observed in the lateralized
      readiness potential (LRP) but not in the peak latency of the P300. In accordance
      with Keus and colleagues (Keus, Jenks, & Schwarz, 2005), we argue that the locus
      of the conflict is situated at intermediate response-related stages. However,
      instead of adopting a single-route processing architecture, a dual route account
      is proposed as the underlying processing architecture explaining the SNARC
      effect.

PMID- 16610274
TI  - Employing automatic approach and avoidance tendencies for the assessment of
      implicit personality self-concept: The implicit association procedure (IAP).
AB  - A new chronometric procedure, the Implicit Association Procedure (IAP), was
      adapted to assess the implicit personality self-concept of shyness. A sample of
      300 participants completed a shyness-inducing role play and, before or after the
      role play, a shyness IAP, a shyness Implicit Association Test (IAT), and direct
      self-ratings. The experimental group was instructed to fake nonshyness. The
      control group did not receive this instruction. IAT and IAP were unaffected by
      position effects, and were less susceptible to faking than direct self-ratings
      with regard to mean levels and correlates. Under faking, correlations between
      direct and indirect measures decreased, and direct but not indirect measures
      showed higher correlations with social desirability and lower correlations with
      observed shyness. Despite many similarities, the true correlation between IAT and
      IAP was estimated only .61, indicating high method-specific variance in both
      procedures. The findings suggest that indirect measures are more robust against
      faking than traditional self-ratings but do not yet meet psychometric criteria
      for practical assessment purposes.

PMID- 16610275
TI  - Effects of belief and logic on syllogistic reasoning: Eye-movement evidence for
      selective processing models.
AB  - Studies of syllogistic reasoning have demonstrated a nonlogical tendency for
      people to endorse more believable conclusions than unbelievable ones. This belief
      bias effect is more dominant on invalid syllogisms than valid ones, giving rise
      to a logic by belief interaction. We report an experiment in which participants'
      eye movements were recorded in order to provide insights into the nature and time
      course of the reasoning processes associated with manipulations of conclusion
      validity and believability. Our main dependent measure was people's inspection
      times for syllogistic premises, and we tested predictions deriving from three
      contemporary mental-models accounts of the logic by belief interaction. Results
      supported recent "selective processing" theories of belief bias (e.g., Evans,
      2000; Klauer, Musch, & Naumer, 2000), which assume that the believability of a
      conclusion biases model construction processes, rather than biasing the search
      for falsifying models (e.g., Oakhill & Johnson-Laird, 1985) or a response stage
      of reasoning arising from subjective uncertainty (e.g., Quayle & Ball, 2000). We
      conclude by suggesting that the eye-movement analyses in reasoning research may
      provide a useful adjunct to other process-tracing techniques such as verbal
      protocol analysis.

PMID- 16610276
TI  - [Methods for increasing the efficiency of aerosol inhalators].
AB  - Methods for increasing the efficiency of aerosol inhalation anesthesia and
      therapy are discussed. Certain aspects of aerosol generation, sedimentation in
      the respiratory pathways, and regulation of aerosol particle size are considered.
      Methods of aerosol heating and parameters of heat production in inhalation
      mixtures are analyzed.

PMID- 16610277
TI  - [Estimation of electrode arrangement efficiency in measurement of coordinates of
      dipolar myocardium sources].
AB  - Identification of early disturbances in the process of myocardium depolarization
      and localization of coordinates of these disturbances in the heart contour is an
      urgent problem of modern electrocardiography. To solve this problem, it is
      necessary to identify signals of small disturbances in the depolarization process
      related to particular zones of disturbances in myocardium. Then, the identified
      signals are used to calculate the disturbance coordinates. In this work, a
      technique for estimation of partial sensitivity of electrodes to the position and
      orientation of the dipolar sources in myocardium is suggested. The results of
      calculation of partial sensitivity presented in this work make it possible to
      identify effective electrodes and minimize the total number of electrodes. The
      obtained results enabled us to suggest a system of electrodes for measurement of
      coordinates of the disturbance sources.

PMID- 16610278
TI  - [Optimization of devices for antibiotic phoretic physiotherapy on the basis of a
      two-barrier model of diffusion and diffusion-osmotic migration of antibiotic
      anions].
AB  - One-, two-, three-, and four-component low-amplitude field phoretic effects on
      permeability of placental and muscular biological barriers to levomycetin,
      benzylpenicillin, and oxacillin anions were studied. Experimental data on
      exposure to constant electric fields, sinusoidal alternating magnetic field,
      thermal heating, and vibroacoustic and UHF effects were used to determine the
      mean coefficients of acceleration of antibiotic anion migration through placental
      and muscular barriers. The effect of physical fields was interpreted in terms of
      the sensitivity coefficient, total factor of systemic response of human body, and
      trade-off optimization index. The results of calculation of trade-off
      optimization index showed that the maximal relative therapeutic efficiency was
      observed for optimal numbers of combined fields (2-3) both for placental and
      muscular barriers. The obtained results showed that optimal stimulated migration
      of antibiotic anions in placental or muscular barrier was already observed in two
      component physical fields, such as magnetoelectric, UHF-magnetic, UHF-electric,
      UHF-vibroacoustic, magnetovibroacoustic, electrovibroacoustic, etc. Clinical use
      of stimulated anion migration is illustrated by the example of its
      physiotherapeutic effect in male urology, ophthalmology, dentistry, and dental
      implantation.

PMID- 16610279
TI  - [Experimental determination of the effective atomic number of inclusion tissue by
      spectrozonal roentgenography].
AB  - The results of spectrozonal roentgenographic study performed using a digital
      scanning fluorograph are presented. It is shown that organic inclusions visible
      in X-ray photographs made in different spectral ranges can be differentiated by
      the effective atomic number.

PMID- 16610280
TI  - [A study of the necessity of cooling of charge-coupled devices in x-ray imaging
      systems].
AB  - The goal of this work was to study one of the widely used X-ray imaging systems:
      luminescent screen-optical system-matrix of photosensitive charge-coupled device
      (CCD)-amplifier-analog-to-digital converter. Experimental and theoretical studies
      were performed to substantiate the necessity of cooling of charge-coupled devices
      for improvement of X-ray image characteristics. The obtained results reveal the
      necessity of cooling of CCD-matrix crystals in the X-ray imaging system under
      consideration.

PMID- 16610281
TI  - [Analysis of diagnostic efficiency of lung ventilation parameters in patients
      with bronchial asthma].
AB  - The goal of this work was to perform probabilistic assessment of the diagnostic
      efficiency of lung ventilation parameters in patients with bronchial asthma. The
      efficiency of the suggested method was compared with that of the widely used
      technique of contrast of means. Study was performed in 365 patients with
      bronchial asthma and 216 apparently healthy subjects. Structural analysis of the
      diagnostic efficiency of lung ventilation parameters was performed on the basis
      of pooled and separate estimates. The results of the study made it possible to
      classify the lung ventilation parameters according to the degree of their
      diagnostic validity.

PMID- 16610282
TI  - [Synthesis of radiological models and radiological invariants (constants). Part
      2].
AB  - The goal of this work was to synthesize a mathematical model (MM) on the basis of
      Klepper and Lyman MMs, which describe the probability of post-radiation
      complications (PRC) in tissue subjected to radiation therapy with given scheme of
      dose fractionating (DF), and the LQ-model, which describes equivalent DF schemes
      for a fixed PRC value. Construction of synthesized MMs (SMMs) becomes possible
      only on the basis of several assumptions requiring further clinical validation.
      Synthesized MMs can be used for determination of the optimal dynamic conditions
      of irradiation of malignant tumors. These conditions include the optimal physical
      plan of irradiation and the optimal time scheme of its implementation. Synthesis
      of MMs leads to determination of radiological invariants (constants), which can
      become a basis for a new branch of medical science, quantitative radiology.

PMID- 16610283
TI  - [A method for prevention of exposure of acupuncture points to undesirable
      effects].
AB  - Analysis of currently used medical electrostimulation equipment shows that under
      certain conditions (determined by current characteristics and electrode size) the
      skin is exposed to considerably high electric current. If an electrode is applied
      to skin region containing acupuncture points, unintentional and, therefore,
      uncontrollable exposure to electric current can have a detrimental effect on the
      health and the functional state of human body. In this work, an algorithm for
      preventing unintentional exposure of acupuncture points to electrostimulation is
      considered. The algorithm can be implemented using special electrodes consisting
      of insulated segments. Electric commutation of segments makes it possible to
      change automatically the working configuration of electrodes.

PMID- 16610284
TI  - [Correction of acute stress-induced disorders of hemostasis using KVCh-NO
      apparatus].
AB  - The effect of electromagnetic terahertz oscillations at frequencies of the
      molecular spectrum of nitric oxide radiation and absorption (150.176-150.664 GHz)
      on the properties of blood coagulation in white laboratory rats subjected to
      immobilization stress was studied. It was shown that exposure of animals to
      terahertz electromagnetic radiation led to normalization of disordered blood
      coagulation. The efficiency of the procedure depended on its duration.

PMID- 16610285
TI  - [Design principles, structure, and specific features of kardiovid computer
      diagnostic system].
AB  - The design principles and hardware implementation of Kardiovid computer
      diagnostic system are considered. The system is intended for diagnosis of the
      state of cardiovascular system on the basis of the results of
      electrocardiographic and fluorographic examinations. It provides simulation and
      visualization of the state of cardiovascular system.

PMID- 16610286
TI  - [A pH-probe for endoscopic parietal topographical pH-metry].
AB  - A pH-probe for endoscopic parietal topographical pH-metry was developed. The
      probe has a circular measuring electrode and a cutaneous silver chloride
      reference electrode. Clinical testing of the developed probe was performed to
      compare it with a conventional end electrode. It was found that the new pH-probe
      with circular antimonial electrode for pH measurement at the surface of the
      mucous coat of upper gastrointestinal tract in a fasting patient considerably
      increases the accuracy of pH measurement at the site of acid glands.
      Recommendations for examination of acid-forming and alkalizing functions of
      stomach and determination of the boundaries of the main regions of stomach during
      endoscopic examination are given.

PMID- 16610287
TI  - [A spiroarteriocardiorhythmograph].
AB  - The design and principle of operation of a spiroarteriocardiorhythmograph are
      described. The device provides continuous noninvasive measurement of arterial
      pressure, detection of inhaled and exhaled air flows with a high-sensitivity
      ultrasonic spirometr, electrocardiogram detection, and joint analysis of these
      dynamal processes. Continuous measurement of pressure is performed by the method
      suggested by Penaz. The method is based on assessment of the volume of blood
      vessels of patient's finger from photoplethysographic signal. An electropneumatic
      follow-up system produces essure counteracting the changes in the diameter of
      arterial vessels patient's finger under the cuff. Thus, the diameter of the
      finger arteries remains constant, and the pressure in the cuff is equal to blood
      pressure in the arteries. This provides a unique opportunity for long-term
      detection of the entire curve of arterial pressure. Previously, such measurements
      could be performed only by the invasive Oxford technique.

PMID- 16610288
TI  - [Development of systems for digital fluorography and roentgenography on the basis
      of x-ray image intensifiers (XRII)].
AB  - A comparative review of characteristics of digital detectors for fluorography and
      roentgenography. Modern digital detection systems on the basis of X-ray image
      intensifiers (XRII) were demonstrated to be superior in terms of both X-ray image
      parameters and radiation safety of patient. Specifications of a new detection
      system for fluorography and roentgenography available from SpektrAP Ltd. (Russia)
      were described.

PMID- 16610289
TI  - [A cassette with a mechanism for removal of radiographic film].
AB  - In this work, a cassette with the lift of radiographic film is described. The
      lift is implemented using a lever fastened to a blade located outside the frame.
      The level is connected to two platforms (L-shaped and P-shaped) via two
      lightproof holes. The platforms are placed inside the frame at angles equal to
      the slope angle of one of the shorter sides of the radiographic film. Removal of
      the radiographic film is performed without damage to its emulsion coating,
      scratching, or bending of the intensifying cassette screens. The procedure of
      labeling of X-ray film is simplified.

PMID- 16610290
TI  - [The history of oximetry].
AB  - Presently, pulsoximeters are very common devices used in every surgical
      operation. Unique properties of pulsoximeter (safety, accuracy, and efficiency)
      enable physician to monitor oxygen-transporting function of blood, which is a
      vitally important function of human body. The history of pulsoximetry dates back
      to several generations ago, researchers of many countries being involved in the
      invention of this device. The idea of pulsoximetry has been updated at each stage
      of technological progress. The history of pulsoximetry illustrates progressively
      increasing importance of spectrophotometric method in medicine and its
      perspectives for the future.

PMID- 16610291
TI  - Home care: we want more.

PMID- 16610292
TI  - A sabbatical journey of discovery: patient safety.

PMID- 16610293
TI  - A dialogue on quality and patient safety with Maureen Bisognano. Interview by G.
      Ross Baker.

PMID- 16610294
TI  - A focus on nursing human resources.

PMID- 16610295
TI  - Nursing human resources: what do we know?

PMID- 16610296
TI  - Evaluating our RN recruitment plan.

PMID- 16610297
TI  - Delivery of high-tech home care by hospital-based nursing units in Quebec:
      clinical and technical challenges.
AB  - BACKGROUND: The role that hospital-based nurses should play in the delivery of
      high-tech home care, and how they should be supported in that role, are topics
      that remain understudied. Our research objective was to document how hospital
      based nursing teams perceive and deal with the clinical and technical challenges
      associated with the provision of high-tech home care. METHODS: Four home care
      interventions were selected: antibiotic intravenous therapy, parenteral
      nutrition, peritoneal dialysis and oxygen therapy. A self-administered survey was
      sent to all hospital-based units providing these interventions in the province of
      Quebec, Canada (n = 154; response rate: 70.8%). We used descriptive statistical
      analyses to derive mean values for scores on either a five- or a six-level Likert
      scale. RESULTS: Despite variation across the four interventions, our results
      indicate that while nursing teams believe these interventions increase patients'
      autonomy, they also recognize that they generate anxiety and impose constraints
      on patients' lives. Nurses must increase efforts to deal with both clinical and
      technical challenges and help patients overcome the barriers to appropriate use
      of home care technologies. CONCLUSIONS: While nursing teams generally perceive
      high-tech home care as beneficial, they still experience significant technical
      and clinical challenges. Some of these challenges could be addressed by
      strengthening professional training initiatives, while others require broader
      home care policy interventions.

PMID- 16610298
TI  - Impoverishment of practice: analysis of effects of economic discourses in home
      care case management practice.
AB  - Home care is a health sector under increasing pressure. Demand is often said to
      be outstripping capacity, with constant change and retrenchment distinguishing
      features of the current context. This paper takes a reading of the current
      conditions of home care using data gathered during a field study of home care
      case management practices conducted in 2004. As economic discourses become
      increasingly influential in determining responses to client situations, case
      managers (and their managers) find themselves with limited capacity to exercise
      control over their practices. A growing gap between professionally influenced
      discourses--those presumably intended to guide practice--and organizational
      priorities creates a dissonance for case managers as the political-ethical
      dimensions of their practices are displaced by budget "realities." For front-line
      workers, such displacement cannot be sustained in their face-to-face encounters
      with clients, leading to a growing sense of frustration and powerlessness among
      these highly skilled practitioners.

PMID- 16610299
TI  - Processes of care: comparison between nurse practitioners and physician residents
      in acute care.
AB  - The purpose of this study was to compare the processes of care (performance of
      role functions, provision of comprehensive care, coordination of services) of
      acute care nurse practitioners (ACNPs) and physician residents (PRs) assigned to
      various medical and surgical programs in acute care settings. A cross-sectional
      comparative design was used. ACNPs (n = 31) and PRs (n = 10) completed the study
      questionnaire within two weeks of consenting. Patients who received ACNP care (n
      = 320) and those who received PR care (n = 46) completed the questionnaire within
      one week of discharge. The results indicate that ACNPs engaged in management and
      informal coordination activities more than PRs did, while PRs engaged in more
      formal coordination activities compared to ACNPs. ACNPs encouraged more patient
      participation in care and provided more patient education than PRs. These
      findings, which reflect differences in the processes used by ACNPs and PRs to
      provide care to patients, could influence the quality and cost outcomes expected
      of these two groups of healthcare providers.

PMID- 16610300
TI  - [The creative activity of Academician L. K. Bogush, the founder of the Russian
      and Soviet School of Phthisiosurgeons].

PMID- 16610301
TI  - [Thirty-five years' experience of thoracic surgery].
AB  - The paper pools the experience gained in the surgical treatment of lung
      malformations in children and adults, which has been used to develop their
      current classification. It also presents the outcomes of surgical treatment of
      acute infectious lung destructions, by taking into account the Marchuk severity
      index. Modes of surgical treatment of bullous pulmonary emphysema have been
      provided, which yield minimum postoperative mortality rates (3%). The experience
      of surgical treatment of 110 patients with cicatrical tracheal stenosis is
      summarized. The authors also present the results of operations made in 390
      patients with Stage III non-small cell carcinoma of the lung, specify indications
      and procedures for resection of the bifurcation of the trachea when the latter is
      involved in the tumorous process. They also summarize the experience gained in
      having performed more than 300 operations in the past 5 years for progressive
      pulmonary tuberculosis, with 2.7% mortality, and 106 final pneumonectomies for
      postoperative recurrent pulmonary tuberculosis. The experience with allografting
      of the trachea (n = 2) and lung (n = 3) is important and little studied in our
      country.

PMID- 16610302
TI  - [Bogush's role in the development and improvement of anesthesiological service in
      phthisiosurgery].

PMID- 16610303
TI  - [L. K. Bogush's role in the development of surgical treatment for tuberculosis
      and other respiratory pathology in children and adolescents].
AB  - The paper briefly describes data on the first operations on the lung made in
      children at the Central Research Institute of Tuberculosis for pulmonary
      tuberculosis under anesthesia. According to L. K. Bogush's recommendations, the
      author has first made clinicomorphological and bacteriological comparisons of
      different pathological tissue from 105 children and adolescents operated on for
      pulmonary tuberculosis, 81 biopsy specimens being abacillary. Mycobacterium
      tuberculosis was found in 54.3% of the operative biopsy specimens from the
      patients long (mean 1.5 to 2 years) treated by antibiotics. L. K. Bogush defined
      indications for surgical treatment for different clinical forms of pulmonary
      tuberculosis in children and adolescents. Six hundred and twenty-seven operations
      were performed in 589 children and adolescents. All types and volumes of lung
      resections, pneumonectomy, pleuropneumonectomy, pleurectomy,
      lymphonudulectomy(tomy), and main bronchi occlusion were made. Operations were
      performed mainly via lateral access, without crossing the ribs.

PMID- 16610304
TI  - [Impact of phthisiosurgery on the development of morphological studies of the
      lung].
AB  - The paper describes the most important developmental stages of phthisiomorphology
      in chronological order, by using as an example the work of the Pathomorphology
      Laboratory, Central Tuberculosis Research Institute, since its organization. It
      also shows the stages of phthisiosurgery with the inestimable scientific and
      practical contribution of the works by L. K. Bogush and his followers from the
      formation of lung surgery to today's achievements. The authors give examples of
      the long-term working partnership of surgeons and morphologists in the
      development of these two disciplines, which was fruitful in deciding many issues
      of phthisiology.

PMID- 16610305
TI  - [Biochemistry in the formation of modern phthisiosurgery: its role and
      prospects].
AB  - The paper reviews the development of biochemical studies in phthisiosurgery, by
      comparing the needs of resuscitation and anesthetic provision of major thoracic
      operations and the management of the postoperative period. Emphasis is laid on
      the leading role of biochemical monitoring in the prevention and treatment of
      postoperative events, such as acute renal failure, metabolic alkalosis,
      thrombohemorrhagic syndrome, pulmonary thromboembolism, and others. The prospects
      of further researches dealing with the problems of postoperative pathophysiology
      are considered in patients with pulmonary tuberculosis.

PMID- 16610306
TI  - [Endocavitary ultraviolet laser irradiation in the preoperative preparation of
      patients with progressive fibrocavernous tuberculosis].
AB  - The authors have improved a procedure for preoperatively preparing patients with
      progressive drug-resistant fibrocavernous tuberculosis. This has been achieved by
      using ultraviolet laser irradiation (wavelength 248 nm) of the cavity walls in
      the multimodality treatment of this disease. Endocavitary laser irradiation
      increases preoperative preparation and surgical treatment and reduces the number
      of postoperative complications.

PMID- 16610307
TI  - [Detection and treatment of Chlamydia and Mycoplasma infections in patients with
      bronchoobstructive diseases].

PMID- 16610308
TI  - [Preponderance of Mycobacterium tuberculosis strains of the family Beijing and
      risk factors of their transmission in the Samara Region].
AB  - Current molecular and epidemiological studies could reveal individual families of
      Mycobacterium tuberculosis strains. The purpose of the present study was to
      reveal the spread of Mycobacterium tuberculosis strains of the family Beijing in
      the Samara Region and to define risk factors for their transmission. This was a
      cross-sectional populational molecular epidemiological study that showed that the
      Beijing genotype prevailed among the obtained isolates (66.6%; 586/880) and it
      was encountered among convicts and young persons (RR 1.3; 95% CI 1.2-1.5 and RR
      1.2; 95% CI 1.0-1.3, respectively), which is indicative of active and recent
      transmission. Multifactorial analysis indicated that male sex (OR 1.5; 95% CI 1.1
      1.9), younger age (OR 1.3; 95% CI 1.1-1.7), homelessness (OR 5.6; 95% CI 1.1
      6.3), and prior or current confinement (OR 2.0; 95 CI 1.5-2.7) were substantially
      associated with the risk of contamination with the strain of the Beijung family.
      Drug resistance, including multidrug resistance, was twice higher among the
      strains of this family.

PMID- 16610309
TI  - [Differential diagnosis of systemic vasculitis and tuberculosis].
AB  - Microbiology, X-ray study, and bronchoscopy, including the examination of
      bronchoalveolar lavage and histology of thransbronchial lung biopsy specimens
      have proven to be of the greatest informative value in the differential diagnosis
      of different forms of systemic vasculitis and tuberculosis in 52 patients. Focal
      pulmonary tuberculosis was detected in the phase of S(II) infiltration on the
      right in a patient with rheumatic arthritis; Mycobacterium tuberculosis was
      bacterioscopically detected. The patient underwent specific antituberculous
      therapy that provided beneficial effects.

PMID- 16610310
TI  - [Scintigraphic studies in phthisiology and thoracic surgery].

PMID- 16610311
TI  - [Evaluation of the course of chronic obstructive lung diseases according to the
      classifications of the European Respiratory Society and the Global Initiative on
      Chronic Obstructive Lung Disease].
AB  - In 91 patients with chronic obstructive lung disease (COLD), the severity of this
      disease according to the Classifications of the European Respiratory Society
      (ERS) and the Global Initiative on Chronic Obstructive Lung Disease (GOLD) was
      compared with that of pulmonary dysfunction according to the data of a
      comprehensive study, involving the determination of bronchial patency, lung
      volumes, capacities, and gas-exchange function. This follows that the ERS and
      GOLD classifications are to be positively appraised as they provide an eligible
      group of patients for clinical practice in terms of the severity of pulmonary
      dysfunction and that of COLD. However, the concomitant clinical use of both
      classifications cannot be regarded as justifiable due to that there are
      differences in the number of detectable grades (stages) of COLD and borderline
      (COLD differentiating grades (stages) values of EFV1). In this connection, both
      classifications have approximately equally significant merits and shortcomings
      and it is practically impossible to give preference to one of them as the best
      one. The optimal way out of the established situation is to develop a new
      (improved) classification of the severity of COLD on the bases of these two
      existing classifications.

PMID- 16610312
TI  - [Tuberculosis and the work of the Central Tuberculosis Research Institute,
      Russian Academy of Medical Sciences, in the years of the Great Patriotic War].

PMID- 16610313
TI  - [Unknown pages of the history of Soviet tuberculosis service].

PMID- 16610314
TI  - The population genetics of sporophytic self-incompatibility in Senecio squalidus
      L. (Asteraceae): the number, frequency, and dominance interactions of S alleles
      across its British range.
AB  - Sporophytic self-incompatibility (SSI) was studied in 11 British Senecio
      squalidus populations to quantify mating system variation and determine how its
      recent colonization of the United Kingdom has influenced its mating behavior. S
      allele number, frequency, and dominance interactions in populations were assessed
      using full diallels of controlled pollinations. A mean of 5.1 S alleles per
      population was observed, and no population contained more than six S alleles.
      Numbers of S alleles within populations of S. squalidus declined with increasing
      distance from the center of its introduction (Oxford). Cross-classification of S
      alleles allowed an estimate of approximately seven and no more than 11 S alleles
      for the entire British S. squalidus population. The low number of S alleles
      observed in British S. squalidus compared to other SI species is consistent with
      the population bottleneck associated with S. squalidus' introduction to the
      Oxford Botanic Garden and subsequent colonization of Britain. Extensive S allele
      dominance interactions were observed to be a feature of the S. squalidus SSI
      system and may represent an adaptive response to improve limited mate
      availability imposed by the presence of so few S alleles. Multilocus allozyme
      genotypes were also identified for individuals in all populations and geographic
      patterns of S locus and allozyme loci variation investigated. Less
      interpopulation structure was observed for the S locus than for allozyme
      diversity--a finding indicative of the effects of negative frequency-dependent
      selection at the S locus maintaining equal S phenotypes within populations and
      enhancing effective migration between populations.

PMID- 16610315
TI  - Intraspecific hybridization and the recovery of fitness in the native legume
      Chamaecrista fasciculata.
AB  - Genetic incompatibilities and low offspring fitness are characteristic outcomes
      of hybridization between species. Yet, the creative potential of recombination
      following hybridization continues to be debated. Here we quantify the outcome of
      hybridization and recombination between adaptively divergent populations of the
      North American legume Chamaecrista fasciculata in a large-scale field experiment.
      Previously, hybrids between these populations demonstrated hybrid breakdown,
      suggesting the expression of adaptive epistatic interactions underlying
      population genetic differentiation. However, the outcome of hybridization
      ultimately rests on the performance of even later generation recombinants. In
      experiments that compared the performance of recombinant F6 and F2 generations
      with nonrecombinant F1 and parental genotypes, we observed that increasing
      recombination had contrasting effects on different life-history components.
      Lifetime fitness, defined as the product of survivorship and reproduction, showed
      a strong recovery of fitness in the F6. The overall gain in fitness with
      increased recombination suggests that hybridization and recombination may provide
      the necessary genetic variation for adaptive evolution within species. We discuss
      the mechanisms that may account for the gain in fitness with recombination, and
      explore the implications for hybrid speciation and phenotypic evolution.

PMID- 16610316
TI  - Impact of insect pollinator group and floral display size on outcrossing rate.
AB  - Despite the strong influence of pollination ecology on the evolution of selfing,
      we have little information on how distinct groups of insect pollinators influence
      outcrossing rate. However, differences in behavior between pollinator groups
      could easily influence how each group affects outcrossing rate. We examined the
      influence of distinct insect pollinator groups on outcrossing rate in the rocky
      mountain columbine, Aquilegia coerulea. The impact of population size, plant
      density, size of floral display, and herkogamy (spatial separation between
      anthers and stigmas) on outcrossing rate was also considered as these variables
      were previously found to affect outcrossing rate in some plant species. We
      quantified correlations between all independent variables and used simple and two
      factor regressions to determine direct and indirect impact of each independent
      variable on outcrossing rate. Outcrossing rate increased significantly with
      hawkmoth abundance but not with the abundance of any of the other groups of
      floral visitors, which included bumblebees, solitary bees, syrphid flies, and
      muscidae. Outcrossing rate was also significantly affected by floral display size
      and together, hawkmoth abundance and floral display size explained 87% of the
      variation in outcrossing rate. None of the other independent variables directly
      affected the outcrossing rate. This is the first report of a significant impact
      of pollinator type on outcrossing rate. Hawkmoths did not visit fewer flowers per
      plant relative to other pollinator groups but preferred visiting female-phase
      flowers first on a plant. Both the behavior of pollinators and floral display
      size affected outcrossing rate via their impact on the level of geitonogamous
      (among flower) selfing. Given that geitonogamous selfing is never advantageous,
      the variation in outcrossing rate and maintenance of mixed mating systems in
      populations of A. coerulea may not require an adaptive explanation.

PMID- 16610317
TI  - Genetic architecture of the cryptic species complex of Acanthocyclops vernalis
      (Crustacea: Copepoda). II. Crossbreeding experiments, cytogenetics, and a model
      of chromosomal evolution.
AB  - Collectively, populations of Acanthocyclops vernalis, a species complex of
      freshwater copepods, are remarkably similar as to morphology and DNA content,
      despite variability in chromosome number. Reproductive isolation had been
      reported among some populations, but with each new investigation the species
      boundaries and factors that may influence them appeared less clear. To clarify
      the pattern of biological species within this group of populations, we adopted a
      comprehensive approach and examined patterns of reproductive isolation in
      populations for which morphology, chromosome number, DNA content, and 18S rDNA
      sequences are known. In this study we established nine isofemale lines from four
      sites in Wisconsin and performed 266 crosses. Crosses within and among these
      lines were used to relate the degree of reproductive isolation to chromosome
      differences and to construct a model to explain the origin and maintenance of
      chromosome number variability. Different gametic and somatic chromosome numbers
      were observed among specimens within some isofemale lines. In a few cases,
      gametes with different haploid numbers were produced by a single female. Matings
      within isofemale lines always produced at least some reproductively successful
      replicate crosses (produced viable, fertile offspring). Crosses between lines
      from the same site showed reduced success relative to within-line crosses.
      Crosses between populations from distant sites showed limited genetic
      compatibility, producing viable, fertile F1 offspring but infertile F2 adults.
      One cross between lines with different chromosome numbers (one with 2n = 8 and
      one with 2n = 10) produced fertile viable offspring, which reproduced for at
      least 60 generations. These hybrids had either eight or nine chromosomes in the
      third generation of inbreeding, and eight chromosomes after 20 generations. These
      hybrids also had reduced nuclear DNA contents at the third generation, a level
      that persisted through the 20th generation. Successful backcrosses between some
      hybrids and their parental lines further demonstrated the potential for genetic
      compatibility among forms with different chromosome numbers. We propose a model
      in which alterations due to Robertsonian fusions, translocations, and/or loss of
      chromosomal fragments generate heritable variation, only some of which leads to
      reproductive isolation. Hence, some of the criteria traditionally used to
      recognize species boundaries in animals (morphology, DNA content, chromosome
      number) may not apply to this species complex.

PMID- 16610318
TI  - Vicariance and dispersal effects on phylogeographic structure and speciation in a
      widespread estuarine invertebrate.
AB  - Vicariance and dispersal can strongly influence population genetic structure and
      allopatric speciation, but their importance in the origin of marine biodiversity
      is unresolved. In transitional estuarine environments, habitat discreteness and
      dispersal barriers could enhance divergence and provide insight to evolutionary
      mechanisms underlying marine and freshwater biodiversity. We examined this by
      assessing phylogeographic structure in the widespread amphipod Gammarus tigrinus
      across 13 estuaries spanning its northwest Atlantic range from Quebec to Florida.
      Mitochondrial cytochrome c oxidase I and nuclear internal transcribed spacer 1
      phylogenies supported deep genetic structure consistent with Pliocene separation
      and cryptic northern and southern species. This break occurred across the
      Virginian-Carolinian coastal biogeographic zone, where an oceanographic
      discontinuity may restrict gene flow. Ten estuarine populations of the northern
      species occurred in four distinct clades, supportive of Pleistocene separation.
      Glaciation effects on genetic structure of estuarine populations are largely
      unknown, but analysis of molecular variance (AMOVA) supported a phylogeographic
      break among clades in formerly glaciated versus nonglaciated areas across Cape
      Cod, Massachusetts. This finding was concordant with patterns in other coastal
      species, though there was no significant relationship between latitude and
      genetic diversity. This supports Pleistocene vicariance events and divergence of
      clades in different northern glacial refugia. AMOVA results and private
      haplotypes in most populations support an allopatric distribution across
      estuaries. Clade mixture zones are consistent with historical colonization and
      human-mediated transfer. An isolation-by-distance model of divergence was
      detected after we excluded a suspected invasive haplotype in the St. Lawrence
      estuary. The occurrence of cryptic species and divergent population structure
      support limited dispersal, dispersed habitat distribution, and historical factors
      as important determinants of estuarine speciation and diversification.

PMID- 16610319
TI  - Adaptation to a steep environmental gradient and an associated barrier to gene
      exchange in Littorina saxatilis.
AB  - Steep environmental gradients offer important opportunities to study the
      interaction between natural selection and gene flow. Allele frequency clines are
      expected to form at loci under selection, but unlinked neutral alleles may pass
      easily across these clines unless a generalized barrier evolves. Here we consider
      the distribution of forms of the intertidal gastropod Littorina saxatilis,
      analyzing shell shape and amplified fragment length polymorphism (AFLP) loci on
      two rocky shores in Britain. On the basis of previous work, the AFLP loci were
      divided into differentiated and undifferentiated groups. On both shores, we have
      shown a sharp cline in allele frequencies between the two morphs for
      differentiated AFLP loci. This is coincident with a habitat transition on the
      shore where the two habitats (cliff and boulder field) are immediately
      contiguous. The allele frequency clines coincide with a cline in shell
      morphology. In the middle of the cline, linkage disequilibrium for the
      differentiated loci rises in accordance with expectation. The clines are
      extremely narrow relative to dispersal, probably as a result of both strong
      selection and habitat choice. An increase in F(ST) for undifferentiated AFLPs
      between morphs, relative to within-morph comparisons, is consistent with there
      being a general barrier to gene flow across the contact zone. These features are
      consistent either with an episode of allopatric divergence followed by secondary
      contact or with primary, nonallopatric divergence. Further data will be needed to
      distinguish between these alternatives.

PMID- 16610320
TI  - Does the desaturase-2 locus in Drosophila melanogaster cause adaptation and
      sexual isolation?
AB  - The desaturase-2 (desat2) locus of Drosophila melanogaster has two alleles whose
      frequencies vary geographically: one (the "Z" allele) is found primarily in east
      Africa and the Caribbean, and the other (the "M" allele) occurs in other parts of
      the world. It has been suggested that these alleles not only cause sexual
      isolation between races, but that their distribution reflects differential
      adaptation to climate: Z alleles are supposedly adapted to tropical conditions
      and M alleles to temperate ones. This has thus been viewed as a case of
      reproductive isolation evolving as a pleiotropic byproduct of adaptation. Here we
      reinvestigate this presumed climatic adaptation, using transgenic lines differing
      in the nature of their desat2 alleles. We were unable to replicate earlier
      results showing that carriers of M alleles are uniformly more cold resistant and
      less starvation resistant than carriers of Z alleles. It is thus doubtful whether
      the distribution of these alleles reflects natural selection involving climate.
      Mating studies of transgenic lines show some evidence for sexual isolation due to
      desat2. However, work on other, wild-type lines, as well as observations on the
      nature of sexual isolation, suggest that this conclusion--and thus the
      relationship between this locus and mating discrimination between races of D.
      melanogaster--may also be doubtful.

PMID- 16610322
TI  - High Wolbachia density correlates with cost of infection for insecticide
      resistant Culex pipiens mosquitoes.
AB  - In the mosquito Culex pipiens, insecticide resistance genes alter many life
      history traits and incur a fitness cost. Resistance to organophosphate
      insecticides involves two loci, with each locus coding for a different mechanism
      of resistance (degradation vs. insensitivity to insecticides). The density of
      intracellular Wolbachia bacteria has been found to be higher in resistant
      mosquitoes, regardless of the mechanism involved. To discriminate between costs
      of resistance due to resistance genes from those associated with elevated
      Wolbachia densities, we compared strains of mosquito sharing the same genetic
      background but differing in their resistance alleles and Wolbachia infection
      status. Life-history traits measured included strength of insecticide resistance,
      larval mortality, adult female size, fecundity, predation avoidance, mating
      competition, and strength of cytoplasmic incompatibility (CI). We found that: (1)
      when Wolbachia are removed, insecticide resistance genes still affect some life
      history traits; (2) Wolbachia are capable of modifying the cost of resistance;
      (3) the cost of Wolbachia infections increases with their density; (4) different
      interactions occurred depending on the resistance alleles involved; and (5) high
      densities of Wolbachia do not increase the strength of CI or maternal
      transmission efficiency relative to low Wolbachia densities. Insecticide
      resistance genes generated variation in the costs of Wolbachia infections and
      provided an interesting opportunity to study how these costs evolve, a process
      generally operating when Wolbachia colonizes a new host.

PMID- 16610323
TI  - Do ants enhance diversification in lycaenid butterflies? Phylogeographic evidence
      from a model myrmecophile, Jalmenus evagoras.
AB  - The ant-tended Australian butterfly, Jalmenus evagoras, has been a model system
      for studying the ecology and evolution of mutualism. A phylogeographic analysis
      of mitochondrial DNA cytochrome oxidase I sequences from 242 butterflies (615 bp)
      and 66 attendant ants (585 bp) from 22 populations was carried out to explore the
      relationship between ant association and butterfly population structure. This
      analysis revealed 12 closely related butterfly haplotypes in three distinct
      clades roughly corresponding to three allopatric subpopulations of the
      butterflies. Minimal genetic diversity and widespread haplotypes within
      biogeographical regions suggest high levels of matrilineal gene flow. Attendant
      ants are significantly more diverse than was previously thought, with at least
      seven well-defined clades corresponding to independent morphological
      determinations, distributed throughout the range of the butterflies. Nested
      analysis of molecular variance showed that biogeography, host plant, and ant
      associate all contribute significantly in explaining variation in butterfly
      genetic diversity, but these variables are not independent of one another. Major
      influences appear to come from fragmentation due to large-scale biogeographical
      barriers, and diversification following a shift in habitat preference. A
      consequence of such a shift could be codiversification of the butterfly with
      habitat-adapted ants, resulting in apparent phylogenetic concordance between
      butterflies and ants. The implications of these results are discussed in terms of
      possible effects of ant attendance on the diversification of Lycaenidae as a
      whole.

PMID- 16610324
TI  - The evolution of unisexuality in Calligrapha leaf beetles: molecular and
      ecological insights on multiple origins via interspecific hybridization.
AB  - Interspecific hybridization is a well-established cause of unisexual origins in
      vertebrates. This mechanism is also suspected in other apomictic taxa, but
      compelling evidence is rare. Here, we evaluate this mechanism and other
      hypotheses for the evolutionary origins of unisexuality through an investigation
      of Calligrapha leaf beetles. This group provides an intriguing subject for
      studies of unisexual evolution because it presents a rare insect example of
      multiple apomictic thelytokous species within a primarily bisexual genus. To
      investigate unisexual evolution, this study conducts the first molecular
      systematic analysis of Calligrapha. This involved the collection and analysis of
      about 3000 bp of DNA sequences--representing RNA and protein-coding loci from
      mitochondrial and nuclear genomes--from 54 specimens of 25 Calligrapha species,
      including four unisexual tetraploid taxa. Phylogenetic and molecular clock
      analyses indicated independent and single evolutionary origins of each of these
      unisexual species during the Pleistocene. Significant phylogenetic incongruence
      was detected between mitochondrial and nuclear datasets and found to be
      especially associated with the asexual taxa. This pattern is expected when
      unisexual lineages arise via interspecific hybridization and thus represent
      genetic mosaics that possess certain nuclear alleles from the paternal species
      lineage and mitochondrial DNA (mtDNA) alleles from the maternal parent. Analyzing
      the mtDNA and nuclear relatedness of unisexuals with corresponding haplotypes of
      bisexual Calligrapha species allowed the putative identification of these
      maternal and paternal species lineages for each unisexual species. Strong
      phenotypic similarities between unisexual taxa and their paternal parent species
      supported a model that involves both backcrosses of interspecific hybrids with a
      paternal parent and unreduced gametes. This model accounts for the origins of
      apomixis, polyploidy, and an overrepresentation of paternal nuclear alleles (and
      associated phenotypes) in unisexuals. This model is also consistent with the
      tetraploid karyotypes of unisexual Calligrapha, in which three sets of
      chromosomes (of presumed paternal ancestry) are quite morphologically homogeneous
      compared to the fourth. Especially intriguing was a consistent association of
      unisexual species with the host plant of the paternal parent but never with the
      maternal host. The statistical implausibility of these patterns occurring by
      chance further supports our inference of parental species. Moreover, it points to
      a potentially critical role for host-association in the formation and
      preservation of unisexual lineages. These findings suggest that ecological
      factors are critical for the diversification of unisexual as well as bisexual
      taxa and thus point out new research directions in the area of ecological
      speciation.

PMID- 16610325
TI  - Cross-generational environmental effects and the evolution of offspring size in
      the Trinidadian guppy Poecilia reticulata.
AB  - The existence of adaptive phenotypic plasticity demands that we study the
      evolution of reaction norms, rather than just the evolution of fixed traits. This
      approach requires the examination of functional relationships among traits not
      only in a single environment but across environments and between traits and
      plasticity itself. In this study, I examined the interplay of plasticity and
      local adaptation of offspring size in the Trinidadian guppy, Poecilia reticulata.
      Guppies respond to food restriction by growing and reproducing less but also by
      producing larger offspring. This plastic difference in offspring size is of the
      same order of magnitude as evolved genetic differences among populations. Larger
      offspring sizes are thought to have evolved as an adaptation to the competitive
      environment faced by newborn guppies in some environments. If plastic responses
      to maternal food limitation can achieve the same fitness benefit, then why has
      guppy offspring size evolved at all? To explore this question, I examined the
      plastic response to food level of females from two natural populations that
      experience different selective environments. My goals were to examine whether the
      plastic responses to food level varied between populations, test the consequences
      of maternal manipulation of offspring size for offspring fitness, and assess
      whether costs of plasticity exist that could account for the evolution of mean
      offspring size across populations. In each population, full-sib sisters were
      exposed to either a low- or high-food treatment. Females from both populations
      produced larger, leaner offspring in response to food limitation. However, the
      population that was thought to have a history of selection for larger offspring
      was less plastic in its investment per offspring in response to maternal mass,
      maternal food level, and fecundity than the population under selection for small
      offspring size. To test the consequences of maternal manipulation of offspring
      size for offspring fitness, I raised the offspring of low- and high-food mothers
      in either low- or high-food environments. No maternal effects were detected at
      high food levels, supporting the prediction that mothers should increase
      fecundity rather than offspring size in noncompetitive environments. For
      offspring raised under low food levels, maternal effects on juvenile size and
      male size at maturity varied significantly between populations, reflecting their
      initial differences in maternal manipulation of offspring size; nevertheless, in
      both populations, increased investment per offspring increased offspring fitness.
      Several correlates of plasticity in investment per offspring that could affect
      the evolution of offspring size in guppies were identified. Under low-food
      conditions, mothers from more plastic families invested more in future
      reproduction and less in their own soma. Similarly, offspring from more plastic
      families were smaller as juveniles and female offspring reproduced earlier. These
      correlations suggest that a fixed, high level of investment per offspring might
      be favored over a plastic response in a chronically low-resource environment or
      in an environment that selects for lower reproductive effort.

PMID- 16610326
TI  - Shared and unique features of diversification in Greater Antillean Anolis
      ecomorphs.
AB  - Examples of convergent evolution suggest that natural selection can often produce
      predictable evolutionary outcomes. However, unique histories among species can
      lead to divergent evolution regardless of their shared selective pressures-and
      some contend that such historical contingencies produce the dominant features of
      evolution. A classic example of convergent evolution is the set of Anolis lizard
      ecomorphs of the Greater Antilles. On each of four islands, anole species
      partition the structural habitat into at least four categories, exhibiting
      similar morphologies within each category. We assessed the relative importance of
      shared selection due to habitat similarity, unique island histories, and unique
      effects of similar habitats on different islands in the generation of
      morphological variation in anole ecomorphs. We found that shared features of
      diversification across habitats were of greatest importance, but island effects
      on morphology (reflecting either island effects per se or phylogenetic
      relationships) and unique aspects of habitat diversification on different islands
      were also important. There were three distinct cases of island-specific habitat
      diversification, and only one was confounded by phylogenetic relatedness. The
      other two unique aspects were not related to shared ancestry but might reflect as
      yet-unmeasured environmental differences between islands in habitat
      characteristics. Quantifying the relative importance of shared and unique
      responses to similar selective regimes provides a more complete understanding of
      phenotypic diversification, even in this much-studied system.

PMID- 16610321
TI  - Extensive introgression of mitochondrial DNA relative to nuclear genes in the
      Drosophila yakuba species group.
AB  - Studies of gene flow between recently diverged species can illuminate the role of
      natural selection in the formation of new species. Drosophila santomea and D.
      yakuba are recently diverged, partially reproductively isolated species that
      continue to hybridize in the wild, and appear to be reproductively isolated from
      the more distantly related species D. teissieri. We examine patterns of
      nucleotide polymorphism and divergence in these three species at multiple X
      linked, Y-linked, and mitochondrial markers. All three species harbor drastically
      reduced variability on the Y chromosome relative to the X, as expected for a
      nonrecombining chromosome subject to variation-reducing selection. The three
      species are generally well differentiated at the nuclear markers, with little
      evidence for recent introgression for either the X- or Y-linked genes. Based on
      the nuclear genes, we estimate that D. santomea and D. yakuba diverged about one
      half million years ago and split from D. teissieri about one million years ago.
      In contrast to the pattern at nuclear loci, all three species share a very
      similar mtDNA haplotype. We show that the mtDNA must have recently introgressed
      across species boundaries in the D. yakuba subgroup and that its fixation was
      driven by either selection on the mitochondria itself or other cytoplasmic
      factors. These results demonstrate that different regions of the genome can have
      distinct evolutionary dynamics in the context of species formation. Although
      natural selection is usually thought of as accentuating divergence between
      species, our results imply that it can also act as a homogenizing force.

PMID- 16610327
TI  - The origin and diversification of Galapagos mockingbirds.
AB  - Evolutionary radiations of colonists on archipelagos provide valuable insight
      into mechanisms and modes of speciation. The apparent diversification of
      Galapagos mockingbirds (Nesomimus) provoked Darwin's initial conception of
      adaptive radiation, but the monophyly of this historically important exemplar has
      not been evaluated with molecular data. Additionally, as with most Galapagos
      organisms, we have a poor understanding of the temporal pattern of
      diversification of the mockingbirds following colonization(s) from source
      populations. Here we present a molecular phylogeny of Galapagos and other
      mockingbird populations based on mitochondrial sequence data. Monophyly of
      Galapagos mockingbirds was supported, suggesting a single colonization of the
      archipelago followed by diversification. Our analyses also indicate that
      Nesomimus is nested within the traditional genus Mimus, making the latter
      paraphyletic, and that the closest living relatives of Galapagos mockingbirds
      appear to be those currently found in North America, northern South America, and
      the Caribbean, rather than the geographically nearest species in continental
      Ecuador. Thus, propensity for over-water dispersal may have played a more
      important role than geographic proximity in the colonization of Galapagos by
      mockingbirds. Within Galapagos, four distinct mitochondrial DNA clades were
      identified. These four clades differ from current taxonomy in several important
      respects. In particular, mockingbirds in the eastern islands of the archipelago
      (Espanola, San Cristobal, and Genovesa) have very similar mitochondrial DNA
      sequences, despite belonging to three different nominal species, and mockingbirds
      from Isabela, in the west of the archipelago, are more phylogenetically divergent
      than previously recognized. Consistent with current taxonomy is the phylogenetic
      distinctiveness of the Floreana mockingbird (N. trifasciatus) and close
      relationships among most mockingbirds from the central and northern region of the
      archipelago (currently considered conspecific populations of N. parvulus).
      Overall, phylogeographic patterns are consistent with a model of wind-based
      dispersal within Galapagos, with colonization of more northerly islands by birds
      from more southern populations, but not the reverse. Further radiation in
      Galapagos would require coexistence of multiple species on individual islands,
      but this may be prevented by relatively limited morphological divergence among
      mockingbirds and by lack of sufficient habitat diversity in the archipelago to
      support more than one omnivorous mimid.

PMID- 16610328
TI  - Major histocompatibility alleles associated with local resistance to malaria in a
      passerine.
AB  - Malaria parasites are a major cause of human mortality in tropical countries and
      a potential threat for wildlife, as witnessed by the malaria-induced extinction
      of naive Hawaiian avifauna. Identifying resistance mechanisms is therefore
      crucial both for human health and wildlife conservation. Patterns of malaria
      resistance are known to be highly polygenic in both humans and mice, with marked
      contributions attributed to major histocompatibility (Mhc) genes. Here we show
      that specific Mhc variants are linked to both increased resistance and
      susceptibility to malaria infection in a wild passerine species, the house
      sparrow (Passer domesticus). In addition, links between host immunogenetics and
      resistance to malaria involved population-specific alleles, suggesting local
      adaptation in this host-parasite interaction. This is the first evidence for a
      population-specific genetic control of resistance to malaria in a wild species.

PMID- 16610329
TI  - Life-history and ecological correlates of geographic variation in egg and clutch
      mass among passerine species.
AB  - Broad geographic patterns in egg and clutch mass are poorly described, and
      potential causes of variation remain largely unexamined. We describe
      interspecific variation in avian egg and clutch mass within and among diverse
      geographic regions and explore hypotheses related to allometry, clutch size, nest
      predation, adult mortality, and parental care as correlates and possible
      explanations of variation. We studied 74 species of Passeriformes at four
      latitudes on three continents: the north temperate United States, tropical
      Venezuela, subtropical Argentina, and south temperate South Africa. Egg and
      clutch mass increased with adult body mass in all locations, but differed among
      locations for the same body mass, demonstrating that egg and clutch mass have
      evolved to some extent independent of body mass among regions. A major portion of
      egg mass variation was explained by an inverse relationship with clutch size
      within and among regions, as predicted by life-history theory. However, clutch
      size did not explain all geographic differences in egg mass; eggs were smallest
      in South Africa despite small clutch sizes. These small eggs might be explained
      by high nest predation rates in South Africa; life-history theory predicts
      reduced reproductive effort under high risk of offspring mortality. This
      prediction was supported for clutch mass, which was inversely related to nest
      predation but not for egg mass. Nevertheless, clutch mass variation was not fully
      explained by nest predation, possibly reflecting interacting effects of adult
      mortality. Tests of the possible effects of nest predation on egg mass were
      compromised by limited power and by counterposing direct and indirect effects.
      Finally, components of parental investment, defined as effort per offspring,
      might be expected to positively coevolve. Indeed, egg mass, but not clutch mass,
      was greater in species that shared incubation by males and females compared with
      species in which only females incubate eggs. However, egg and clutch mass were
      not related to effort of parental care as measured by incubation attentiveness.
      Ecological and life-history correlates of egg and clutch mass variation found
      here follow from theory, but possible evolutionary causes deserve further study.

PMID- 16610330
TI  - Structural complexity of the environment affects the survival of alternative male
      reproductive tactics.
AB  - Alternative reproductive tactics in males are often associated with divergent
      phenotypes expressed as phenotypically plastic threshold traits. The evolution of
      threshold traits in these species has been modeled under the conditional
      evolutionarily stable strategy (ESS). Both strategic and genetic models predict
      that perturbations to the fitness trade-off between the male morphs will lead to
      a shift in the ESS switch point of the threshold. So far, demographic factors
      that influence the competitive ability of male morphs have been investigated and
      related to intraspecific population variation in male dimorphic thresholds. Here
      we reveal evidence for the theoretical prediction that abiotic features of the
      environment, in particular its structural complexity, are likely to influence the
      ESS threshold. In the male dimorphic mite Sancassania berlesei, we monitored the
      survival of aggressive fighter males and their benign scrambler counterparts in
      populations that differed in structural complexity. We found that, consistent
      with our prediction, the complex habitat favored fighter males, enabling them to
      kill a greater number of rival scramblers. We found no effect of habitat
      complexity on the survival of fighter males. These results demonstrate how
      abiotic as well as biotic aspects of the environment can be important in
      determining the frequencies of males adopting alternative tactics in different
      species or populations.

PMID- 16610331
TI  - Male pregnancy and the evolution of body segmentation in seahorses and
      pipefishes.
AB  - The evolution of complex traits, which are specified by the interplay of multiple
      genetic loci and environmental effects, is a topic of central importance in
      evolutionary biology. Here, we show that body and tail vertebral numbers in
      fishes of the pipefish and seahorse family (Syngnathidae) can serve as a model
      for studies of quantitative trait evolution. A quantitative genetic analysis of
      body and tail vertebrae from field-collected families of the Gulf pipefish,
      Syngnathus scovelli, shows that both traits exhibit significantly positive
      additive genetic variance, with heritabilities of 0.75 +/- 0.13 (mean +/-
      standard error) and 0.46 +/- 0.18, respectively. We do not find any evidence for
      either phenotypic or genetic correlations between the two traits. Pipefish are
      characterized by male pregnancy, and phylogenetic consideration of body
      proportions suggests that the position of eggs on the pregnant male's body may
      have contributed to the evolution of vertebral counts. In terms of numbers of
      vertebrae, tail-brooding males have longer tails for a given trunk size than do
      trunk-brooding males. Overall, these results suggest that vertebral counts in
      pipefish are heritable traits, capable of a response to selection, and they may
      have experienced an interesting history of selection due to the phenomenon of
      male pregnancy. Given that these traits vary among populations within species as
      well as among species, they appear to provide an excellent model for further
      research on complex trait evolution. Body segmentation may thus afford excellent
      opportunities for comparative study of homologous complex traits among disparate
      vertebrate taxa.

PMID- 16610332
TI  - The tempo of avian diversification: a comment on Johnson and Cicero.
AB  - Johnson and Cicero (2004) claimed that inspection of a distribution of
      uncorrected mitochondrial DNA avian sister-taxon distances illustrated that the
      late Pleistocene was an important time for avian speciation. They believed this
      finding to be at odds with conclusions of Klicka and Zink (1997). However, both
      studies document recent speciation events. More germane to the discussion is what
      is meant by an "important" time for speciation, which we take to mean above some
      baseline diversification rate. We constructed a null distribution of sister-taxon
      distances based on a model of constant speciation and extinction rates. The
      empirical distribution of sister-taxon distances in Johnson and Cicero (2004) did
      not differ from the null model. Therefore, our analysis of Johnson and Cicero's
      data suggests that the late Pleistocene was no more important for avian
      speciation than any other time during this time period.

PMID- 16610333
TI  - Re-evaluating Russia's biological weapons policy, as reflected in the Criminal
      Code and Official Admissions: insubordination leading to a president's
      subordination.
AB  - Half-heartedly acknowledged by the Russian Federation, the Soviet Union ran the
      world's largest offensive program for biological weapons, breaching the
      Biological and Toxin Weapons Convention. Russia criminalized biological weapons
      in 1993 only to decriminalize them in 1996, but in 2003 president Putin partly
      recriminalized them. None of these changes were declared within the Convention.
      Several well-known official statements, when reviewed in their context, turned
      out to admit to neither an offensive program nor a breach of the Convention.
      Thus, the Russian biological weapons policy is more ambiguous than usually
      depicted, and various policy shapers can be discerned.

PMID- 16610334
TI  - The Soviet anti-plague system: an introduction.
AB  - This article describes the composition of the Soviet Anti-plague (AP) system and
      presents the methodology used by the authors in their study of the AP system.

PMID- 16610335
TI  - Genesis of the anti-plague system: the Tsarist period.
AB  - Although the anti-plague system of the former Soviet Union developed fully during
      the Soviet era, its foundations were laid long before the Bolshevik Revolution of
      1917. This article traces the evolution of the anti-plague measures from
      imposition of temporary quarantine in affected areas to the creation of the
      standard response system and the establishment of permanent anti-plague
      organizations. The purpose of this article is to demonstrate that by the end of
      the nineteenth century and the beginning of the twentieth century, despite
      numerous setbacks, the Russian imperial authorities succeeded in creating a
      nascent system of disease surveillance dedicated to protecting the population
      from especially dangerous infectious diseases such as plague.

PMID- 16610336
TI  - Growth of the anti-plague system during the Soviet period.
AB  - The Anti-plague system experienced a dramatic expansion in Soviet times. From the
      dozen facilities created in the Russian Empire, it grew during the Soviet period
      to include over 100 facilities engaged in public health activities as well as BW
      related work. This article describes how this highly responsive public health
      system, created to respond to natural outbreaks of dangerous diseases, became a
      critical adjunct to the Soviet BW program.

PMID- 16610337
TI  - The anti-plague system and the Soviet biological warfare program.
AB  - The USSR possessed a unique national public health system that included an agency
      named "anti-plague system." Its mission was to protect the country from highly
      dangerous diseases of either natural or laboratory etiology. During the 1960s,
      the anti-plague system became the lead agency of a program to defend against
      biological warfare, codenamed Project 5. This responsibility grew and by the
      middle 1970s came to include undertaking tasks for the offensive biological
      warfare program, codenamed Ferment. This article describes the anti-plague
      system's activities relevant to both aspects of the Soviet Union's biological
      warfare program, offense and defense, and analyzes its contributions to each.

PMID- 16610338
TI  - What non-proliferation policy for the Soviet anti-plague system?
AB  - This article analyzes the proliferation challenges posed by the Soviet AP system
      and discusses possible nonproliferation strategies to prevent these threats.

PMID- 16610339
TI  - History of arrhythmias.
AB  - A historical overview is given on the techniques to record the electrical
      activity of the heart, some anatomical aspects relevant for the understanding of
      arrhythmias, general mechanisms of arrhythmias, mechanisms of some specific
      arrhythmias and nonpharmacological forms of therapy. The unravelling of
      arrhythmia mechanisms depends, of course, on the ability to record the electrical
      activity of the heart. It is therefore no surprise that following the
      construction of the string galvanometer by Einthoven in 1901, which allowed high
      fidelity recording of the body surface electrocardiogram, the study of
      arrhythmias developed in an explosive way. Still, papers from McWilliam (1887),
      Garrey (1914) and Mines (1913, 1914) in which neither mechanical nor electrical
      activity was recorded provided crucial insights into re-entry as a mechanism for
      atrial and ventricular fibrillation, atrioventricular nodal re-entry and
      atrioventricular re-entrant tachycardia in hearts with an accessory
      atrioventricular connection. The components of the electrocardiogram, and of
      extracellular electrograms directly recorded from the heart, could only be well
      understood by comparing such registrations with recordings of transmembrane
      potentials. The first intracellular potentials were recorded with microelectrodes
      in 1949 by Coraboeuf and Weidmann. It is remarkable that the interpretation of
      extracellular electrograms was still controversial in the 1950s, and it was not
      until 1962 that Dower showed that the transmembrane action potential upstroke
      coincided with the steep negative deflection in the electrogram. For many
      decades, mapping of the spread of activation during an arrhythmia was performed
      with a "roving" electrode that was subsequently placed on different sites on the
      cardiac surface with a simultaneous recording of another signal as time
      reference. This method could only provide reliable information if the arrhythmia
      was strictly regular. When multiplexing systems became available in the late
      1970s, and optical mapping in the 1980s, simultaneous registrations could be made
      from many sites. The analysis of atrial and ventricular fibrillation then became
      much more precise. The old question whether an arrhythmia is due to a focal or a
      re-entrant mechanism could be answered, and for atrial fibrillation, for
      instance, the answer is that both mechanisms may be operative. The road from
      understanding the mechanism of an arrhythmia to its successful therapy has been
      long: the studies of Mines in 1913 and 1914, microelectrode studies in animal
      preparations in the 1960s and 1970s, experimental and clinical demonstrations of
      initiation and termination of tachycardias by premature stimuli in the 1960s and
      1970s, successful surgery in the 1980s, the development of external and
      implantable defibrillators in the 1960s and 1980s, and finally catheter ablation
      at the end of the previous century, with success rates that approach 99% for
      supraventricular tachycardias.

PMID- 16610340
TI  - Pacemaker current and automatic rhythms: toward a molecular understanding.
AB  - The ionic basis of automaticity in the sinoatrial node and His-Purkinje system,
      the primary and secondary cardiac pacemaking regions, is discussed. Consideration
      is given to potential targets for pharmacologic or genetic therapies of rhythm
      disorders. An ideal target would be an ion channel that functions only during
      diastole, so that action potential repolarization is not affected, and one that
      exhibits regional differences in expression and/or function so that the primary
      and secondary pacemakers can be selectively targeted. The so-called pacemaker
      current, If, generated by the HCN gene family, best fits these criteria. The
      biophysical and molecular characteristics of this current are reviewed, and
      progress to date in developing selective pharmacologic agents targeting If and in
      using gene and cell-based therapies to modulate the current are reviewed.

PMID- 16610341
TI  - Proarrhythmia.
AB  - The concept that antiarrhythmic drugs can exacerbate the cardiac rhythm
      disturbance being treated, or generate entirely new clinical arrhythmia
      syndromes, is not new. Abnormal cardiac rhythms due to digitalis or quinidine
      have been recognized for decades. This phenomenon, termed "proarrhythmia," was
      generally viewed as a clinical curiosity, since it was thought to be rare and
      unpredictable. However, the past 20 years have seen the recognition that
      proarrhythmia is more common than previously appreciated in certain populations,
      and can in fact lead to substantially increased mortality during long-term
      antiarrhythmic therapy. These findings, in turn, have moved proarrhythmia from a
      clinical curiosity to the centerpiece of antiarrhythmic drug pharmacology in at
      least two important respects. First, clinicians now select antiarrhythmic drug
      therapy in a particular patient not simply to maximize efficacy, but very
      frequently to minimize the likelihood of proarrhythmia. Second, avoiding
      proarrhythmia has become a key element of contemporary new antiarrhythmic drug
      development. Further, recognition of the magnitude of the problem has led to
      important advances in understanding basic mechanisms. While the phenomenon of
      proarrhythmia remains unpredictable in an individual patient, it can no longer be
      viewed as "idiosyncratic." Rather, gradations of risk can be assigned based on
      the current understanding of mechanisms, and these will doubtless improve with
      ongoing research at the genetic, molecular, cellular, whole heart, and clinical
      levels.

PMID- 16610342
TI  - Cardiac Na+ channels as therapeutic targets for antiarrhythmic agents.
AB  - There are many factors that influence drug block of voltage-gated Na+ channels
      (VGSC). Pharmacological agents vary in conformation, charge, and affinity.
      Different drugs have variable affinities to VGSC isoforms, and drug efficacy is
      affected by implicit tissue properties such as resting potential, action
      potential morphology, and action potential frequency. The presence of
      polymorphisms and mutations in the drug target can also influence drug outcomes.
      While VGSCs have been therapeutic targets in the management of cardiac
      arrhythmias, their potential has been largely overshadowed by toxic side effects.
      Nonetheless, many VGSC blockers exhibit inherent voltage- and use-dependent
      properties of channel block that have recently proven useful for the diagnosis
      and treatment of genetic arrhythmias that arise from defects in Na+ channels and
      can underlie idiopathic clinical syndromes. These defective channels suggest
      themselves as prime targets of disease and perhaps even mutation specific
      pharmacological interventions.

PMID- 16610343
TI  - Structural determinants of potassium channel blockade and drug-induced
      arrhythmias.
AB  - Cardiac K+ channels play an important role in the regulation of the shape and
      duration of the action potential. They have been recognized as targets for the
      actions of neurotransmitters, hormones, and anti-arrhythmic drugs that prolong
      the action potential duration (APD) and increase refractoriness. However,
      pharmacological therapy, often for the purpose of treating syndromes unrelated to
      cardiac disease, can also increase the vul- nerability of some patients to life
      threatening rhythm disturbances. This may be due to an underlying propensity
      stemming from inherited mutations or polymorphisms, or structural abnormalities
      that provide a substrate allowing for the initiation of arrhythmic triggers. A
      number of pharmacological agents that have proved useful in the treatment of
      allergic reactions, gastrointestinal disorders, and psychotic disorders, among
      others, have been shown to reduce repolarizing K+ currents and prolong the Q-T
      interval on the electrocardiogram. Understanding the structural determinants of
      K+ channel blockade might provide new insights into the mechanism and rate
      dependent effects of drugs on cellular physiology. Drug-induced disruption of
      cellular repolarization underlies electrocardiographic abnormalities that are
      diagnostic indicators of arrhythmia susceptibility.

PMID- 16610344
TI  - Sodium calcium exchange as a target for antiarrhythmic therapy.
AB  - In search of better antiarrhythmic therapy, targeting the Na/Ca exchanger is an
      option to be explored. The rationale is that increased activity of the Na/Ca
      exchanger has been implicated in arrhythmogenesis in a number of conditions. The
      evidence is strong for triggered arrhythmias related to Ca2+ overload, due to
      increased Na+ load or during adrenergic stimulation; the Na/Ca exchanger may be
      important in triggered arrhythmias in heart failure and in atrial fibrillation.
      There is also evidence for a less direct role of the Na/Ca exchanger in
      contributing to remodelling processes. In this chapter, we review this evidence
      and discuss the consequences of inhibition of Na/Ca exchange in the perspective
      of its physiological role in Ca2+ homeostasis. We summarize the current data on
      the use of available blockers of Na/Ca exchange and propose a framework for
      further study and development of such drugs. Very selective agents have great
      potential as tools for further study of the role the Na/Ca exchanger plays in
      arrhythmogenesis. For therapy, they may have their specific indications, but they
      carry the risk of increasing Ca2+ load of the cell. Agents with a broader action
      that includes Ca2+ channel block may have advantages in other conditions, e.g.
      with Ca2+ overload. Additional actions such as block of K+ channels, which may be
      unwanted in e.g. heart failure, may be used to advantage as well.

PMID- 16610345
TI  - A role for calcium/calmodulin-dependent protein kinase II in cardiac disease and
      arrhythmia.
AB  - More than 20 years have passed since the discovery that a collection of specific
      calcium/calmodulin-dependent phosphorylation events is the result of a single
      multifunctional kinase. Since that time, we have learned a great deal about this
      multifunctional and ubiquitous kinase, known today as calcium/calmodulin
      dependent protein kinase II (CaMKII). CaMKII is interesting not only for its
      widespread distribution and broad specificity but also for its biophysical
      properties, most notably its activation by the critical second messenger complex
      calcium/calmodulin and its autophosphorylating capability. A central role for
      CaMKII has been identified in regulating a diverse array of fundamental cellular
      activities. Furthermore, altered CaMKII activity profoundly impacts function in
      the brain and heart. Recent findings that CaMKII expression in the heart changes
      during hypertrophy, heart failure, myocardial ischemia, and infarction suggest
      that CaMKII may be a viable therapeutic target for patients suffering from common
      forms of heart disease.

PMID- 16610346
TI  - AKAPs as antiarrhythmic targets?
AB  - Phosphorylation of ion channels plays a critical role in the modulation and
      amplification of biophysical signals. Kinases and phosphatases have broad
      substrate recognition sequences. Therefore, the targeting of kinases and
      phosphatases to specific sites enhances the regulation of diverse signaling
      events. Ion channel macromolecular complexes can be formed by the association of
      A-kinase anchoring proteins (AKAPs) or other adaptor proteins directly with the
      channel. The discovery that leucine/isoleucine zippers play an important role in
      the recruitment of phosphorylation-modulatory proteins to certain ion channels
      has permitted the elucidation of specific ion channel macromolecular complexes.
      Disruption of signaling complexes by genetic defects can lead to abnormal
      physiological function. This chapter will focus on evidence supporting the
      concept that ion channel macromolecular complex formation plays an important role
      in regulating channel function in normal and diseased states. Moreover, we
      demonstrate that abnormal complex formation may directly lead to abnormal channel
      regulation by cellular signaling pathways, potentially leading to
      arrhythmogenesis and cardiac dysfunction.

PMID- 16610347
TI  - Beta-blockers as antiarrhythmic agents.
AB  - Drugs that suppress beta-adrenergic signaling by competitively inhibiting agonist
      binding to beta-adrenergic receptors ("beta-blockers") have important
      antiarrhythmic properties. They differ from most other antiarrhythmic agents by
      not directly modifying ion channel function; rather, they prevent the arrhythmia
      promoting actions of beta-adrenergic stimulation. beta-Blockers are particularly
      useful in preventing sudden death due to ventricular tachyarrhythmias associated
      with acute myocardial ischemia, congenital long QT syndrome, and congestive heart
      failure. They are also quite valuable in controlling the ventricular rate in
      patients with atrial fibrillation. This chapter reviews the properties of beta
      adrenoceptor signaling, the basic mechanisms of cardiac arrhythmias on which beta
      blockers act, the ion channel mediators of beta-adrenergic responses, the
      evidence for clinical antiarrhythmic indications for beta-blocker therapy and the
      specific pharmacodynamic and pharmacokinetic properties of beta-blockers that
      differentiate the various agents of this class.

PMID- 16610348
TI  - Experimental therapy of genetic arrhythmias: disease-specific pharmacology.
AB  - The integration between molecular biology and clinical practice requires the
      achievement of fundamental steps to link basic science to diagnosis and
      management of patients. In the last decade, the study of genetic bases of human
      diseases has achieved several milestones, and it is now possible to apply the
      knowledge that stems from the identification of the genetic substrate of diseases
      to clinical practice. The first step along the process of linking molecular
      biology to clinical medicine is the identification of the genetic bases of
      inherited diseases. After this important goal is achieved, it becomes possible to
      extend research to understand the functional impairments of mutant protein(s) and
      to link them to clinical manifestations (genotype-phenotype correlation). In
      genetically heterogeneous diseases, it may be possible to identify locus-specific
      risk stratification and management algorithms. Finally, the most ambitious step
      in the study of genetic disease is to discover a novel pharmacological therapy
      targeted at correcting the inborn defect (locus-specific therapy) or even to
      "cure" the DNA abnormality by replacing the defective gene with gene therapy. At
      present, this curative goal has been successful only for very few diseases. In
      the field of inherited arrhythmogenic diseases, several genes have been
      discovered, and genetics is now emerging as a source of information contributing
      not only to a better diagnosis but also to risk stratification and management of
      patients. The functional characterization of mutant proteins has opened new
      perspectives about the possibility of performing gene-specific or mutation
      specific therapy. In this chapter, we will briefly summarize the genetic bases of
      inherited arrhythmogenic conditions and we will point out how the information
      derived from molecular genetics has influenced the "optimal use of traditional
      therapies" and has paved the way to the development of gene-specific therapy.

PMID- 16610349
TI  - Mutation-specific pharmacology of the long QT syndrome.
AB  - The congenital long QT syndrome is a rare disease in which inherited mutations of
      genes coding for ion channel subunits, or channel interacting proteins, delay
      repolarization of the human ventricle and predispose mutation carriers to the
      risk of serious or fatal arrhythmias. Though a rare disorder, the long QT
      syndrome has provided invaluable insight from studies that have bridged clinical
      and pre-clinical (basic science) medicine. In this brief review, we summarize
      some of the key clinical and genetic characteristics of this disease and
      highlight novel findings about ion channel structure, function, and the causal
      relationship between channel dysfunction and human disease, that have come from
      investigations of this disorder.

PMID- 16610351
TI  - Molecular basis of isolated cardiac conduction disease.
AB  - Cardiac conduction disorders are among the most common rhythm disturbances
      causing disability in millions of people worldwide and necessitating pacemaker
      implantation. Isolated cardiac conduction disease (ICCD) can affect various
      regions within the heart, and therefore the clinical features also vary from case
      to case. Typically, it is characterized by progressive alteration of cardiac
      conduction through the atrioventricular node, His-Purkinje system, with right or
      left bundle branch block and QRS widening. In some instances, the disorder may
      progress to complete atrioventricular block, with syncope and even death. While
      the role of genetic factors in conduction disease has been suggested as early as
      the 1970s, it was only recently that specific genetic loci have been reported.
      Multiple mutations in the gene encoding for the cardiac voltage-gated sodium
      channel (SCN5A), which plays a fundamental role in the initiation, propagation,
      and maintenance of normal cardiac rhythm, have been linked to conduction disease,
      allowing for genotype-phenotype correlation. The electrophysiological
      characterization of heterologously expressed mutant Na+ channels has revealed
      gating defects that consistently lead to a loss of channel function. However,
      studies have also revealed significant overlap between aberrant rhythm
      phenotypes, and single mutations have been identified that evoke multiple
      distinct rhythm disorders with common gating lesions. These new insights
      highlight the complexities involved in linking single mutations, ion-channel
      behavior, and cardiac rhythm but suggest that interplay between multiple factors
      could underlie the manifestation of the disease phenotype.

PMID- 16610352
TI  - HERG trafficking and pharmacological rescue of LQTS-2 mutant channels.
AB  - The human ether-a-go-go-related gene (hERG) encodes an ion channel subunit
      underlying IKr, a potassium current required for the normal repolarization of
      ventricular cells in the human heart. Mutations in hERG cause long QT syndrome
      (LQTS) by disrupting IKr, increasing cardiac excitability and, in some cases,
      triggering catastrophic torsades de pointes arrhythmias and sudden death. More
      than 200 putative disease-causing mutations in hERG have been identified in
      affected families to date, but the mechanisms by which these mutations cause
      disease are not well understood. Of the mutations studied, most disrupt protein
      maturation and reduce the numbers of hERG channels at the membrane. Some
      trafficking-defective mutants can be rescued by pharmacological agents or
      temperature. Here we review evidence for rescue of mutant hERG subunits expressed
      in heterologous systems and discuss the potential for therapeutic approaches to
      correcting IKr defects associated with LQTS.

PMID- 16610350
TI  - Therapy for the Brugada syndrome.
AB  - The Brugada syndrome is a congenital syndrome of sudden cardiac death first
      described as a new clinical entity in 1992. Electrocardiographically
      characterized by a distinct coved-type 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, and less frequently in infants and
      children. The ECG manifestations of the Brugada syndrome are often dynamic or
      concealed and may be revealed or modulated by sodium channel blockers. The
      syndrome may also be unmasked or precipitated by a febrile state, vagotonic
      agents, alpha-adrenergic agonists, beta-adrenergic blockers, tricyclic or
      tetracyclic antidepressants, a combination of glucose and insulin, and
      hypokalemia, as well as by alcohol and cocaine toxicity. An implantable
      cardioverter-defibrillator (ICD) is the most widely accepted approach to therapy.
      Pharmacological therapy aimed at rebalancing the currents active during phase 1
      of the right ventricular action potential is used to abort electrical storms, as
      an adjunct to device therapy, and as an alternative to device therapy when use of
      an ICD is not possible. Isoproterenol and cilostazol boost calcium channel
      current, and drugs like quinidine inhibit the transient outward current, acting
      to diminish the action potential notch and thus suppress the substrate and
      trigger for ventricular tachycardia/fibrillation (VT/VF).

PMID- 16610353
TI  - Chaperones in preventing protein denaturation in living cells and protecting
      against cellular stress.
AB  - A variety of cellular internal and external stress conditions can be classified
      as proteotoxic stresses. Proteotoxic stresses can be defined as stresses that
      increase the fraction of proteins that are in an unfolded state, thereby
      enhancing the probability of the formation of intracellular aggregates. These
      aggregates, if not disposed, can lead to cell death. In response to the
      appearance of damaged proteins, cells induce the expression of heat shock
      proteins. These can function as molecular chaperones to prevent protein
      aggregation and to keep proteins in a state competent for either refolding or
      degradation. Most knowledge of the function and regulation (by co-factors) of
      individual heat shock proteins comes from cell free studies on refolding of heat-
      or chemically denatured, purified proteins. Unlike the experimental situation in
      a test tube, cells contain multiple chaperones and co-factors often moving in and
      out different subcompartments that contain a variety of protein substrates at
      different folding states. Also, within cells folding competes with the
      degradative machinery. In this chapter, an overview will be provided on how the
      main cytosolic/nuclear chaperone Hsp70 is regulated, what is known about its
      interaction with other main cytosolic/nuclear chaperone families (Hsp27, Hsp90,
      and Hsp110), and how it may function as a molecular chaperone in living mammalian
      cells to protect against proteotoxic stresses.

PMID- 16610354
TI  - Feedback regulation of the heat shock response.
AB  - The heat shock response is triggered primarily by nonnative proteins accumulating
      in a stressed cell and results in increased expression of heat shock proteins
      (Hsps), i.e., of chaperones capable of participating in the refolding or
      elimination of nonnative proteins. Best known is the transcriptional part of this
      response that is mediated predominantly by heat shock factor 1 (HSF1). HSF1
      activity is regulated at different levels by Hsps and co-chaperones and is
      modulated further by a number of mechanisms involving other stress-regulated
      aspects of cell metabolism.

PMID- 16610355
TI  - Protein folding in the endoplasmic reticulum and the unfolded protein response.
AB  - In all eukaryotic cells, the endoplasmic reticulum (ER) is an intracellular
      organelle where folding and assembly occurs for proteins destined to the
      extracellular space, plasma membrane, and the exo/endocytic compartments (Kaufman
      1999). As a protein-folding compartment, the ER is exquisitely sensitive to
      alterations in homeostasis, and provides stringent quality control systems to
      ensure that only correctly folded proteins transit to the Golgi and unfolded or
      misfolded proteins are retained and ultimately degraded. A number of biochemical
      and physiological stimuli, such as perturbation in calcium homeostasis or redox
      status, elevated secretory protein synthesis, expression of misfolded proteins,
      sugar/glucose deprivation, altered glycosylation, and overloading of cholesterol
      can disrupt ER homeostasis, impose stress to the ER, and subsequently lead to
      accumulation of unfolded or misfolded proteins in the ER lumen. The ER has
      evolved highly specific signaling pathways called the unfolded protein response
      (UPR) to cope with the accumulation of unfolded or misfolded proteins.
      Elucidation of the molecular mechanisms by which accumulation of unfolded
      proteins in the ER transmits a signal to the cytoplasm and nucleus has led to
      major new insights into the diverse cellular and physiological processes that are
      regulated by the UPR. This chapter summarizes how cells respond to the
      accumulation of unfolded proteins in the cell and the relevance of these
      signaling pathways to human physiology and disease.

PMID- 16610356
TI  - Molecular chaperones in signal transduction.
AB  - Many cellular signaling molecules exist in different conformations corresponding
      to active and inactive states. Transition between these states is regulated by
      reversible modifications, such as phosphorylation, or by binding of nucleotide
      triphosphates, their regulated hydrolysis to diphosphates, and their exchange
      against fresh triphosphates. Specificity and efficiency of cellular signaling is
      further maintained by regulated subcellular localization of signaling molecules
      as well as regulated protein-protein interaction. Hence, it is not surprising
      that molecular chaperones--proteins that are able to specifically interact with
      distinct conformations of other proteins--could per se interfere with cellular
      signaling. Hence, it is not surprising that chaperones have co-evolved as
      integral components of signaling networks where they can function in the
      maturation as well as in regulating the transition between active and inactive
      state of signaling molecules, such as receptors, transcriptional regulators and
      protein kinases. Furthermore, new classes of specific chaperones are emerging and
      their role in histone-mediated chromatin remodeling and RNA folding are under
      investigation.

PMID- 16610357
TI  - Chaperoning of glucocorticoid receptors.
AB  - A multiprotein hsp90/hsp70-based chaperone machinery functions as a 'cradle-to
      grave' system for regulating the steroid binding, trafficking and turnover of the
      glucocorticoid receptor (GR). In an ATP-dependent process where hsp70 and hsp90
      act as essential chaperones and Hop, hsp40, and p23 act as nonessential co
      chaperones, the machinery assembles complexes between the ligand binding domain
      of the GR and hsp90. During GR-hsp90 heterocomplex assembly, the hydrophobic
      ligand-binding cleft is opened to access by steroid, and subsequent binding of
      steroid within the cleft triggers a transformation of the receptor such that it
      engages in more dynamic cycles of assembly/disassembly with hsp90 that are
      required for rapid dynein-dependent translocation to the nucleus. Within the
      nucleus, the hsp90 chaperone machinery plays a critical role both in GR movement
      to transcription regulatory sites and in the disassembly of regulatory complexes
      as the hormone level declines. The chaperone machinery also plays a critical role
      in stabilization of the GR to ubiquitylation and proteasomal degradation. The
      initial GR interaction with hsp70 appears to be critical for the triage between
      hsp90 heterocomplex assembly and preservation of receptor function vs CHIP
      dependent ubiquitylation and proteasomal degradation. The hsp90 chaperone
      machinery is ubiquitous and functionally conserved among eukaryotes, and it is
      possible that all physiologically significant actions of hsp90 require the hsp70
      dependent assembly of client protein-hsp90 heterocomplexes.

PMID- 16610358
TI  - Heat shock response: lessons from mouse knockouts.
AB  - Organisms are endowed with integrated regulatory networks that transduce and
      amplify incoming signals into effective responses, ultimately imparting cell
      death and/or survival pathways. As a conserved cytoprotective mechanism from
      bacteria to humans, the heat shock response has been established as a paradigm
      for inducible gene expression, stimulating the interests of biologists and
      clinicians alike to tackle fundamental questions related to the molecular
      switches, lineage-specific requirements, unique and/or redundant roles, and even
      efforts to harness the response therapeutically. Gene targeting studies in mice
      confirm HSF1 as a master regulator required for cell growth, embryonic
      development, and reproduction. For example, sterility of Hsf1-null female but not
      null male mice established strict requirements for maternal HSF1 expression in
      the oocyte. Yet Hsf2 knockouts by three independent laboratories have not fully
      clarified the role of mammalian HSF2 for normal development, fertility, and
      postnatal neuronal function. In contrast, Hsf4 knockouts have provided a
      consistent demonstration for HSF4's critical role during lens formation. In the
      future, molecular analysis of HSF knockout mice will bring new insights to HSF
      interactions, foster better understanding of gene regulation at the genome level,
      lead to a better integration of the HSF pathway in life beyond heat shock, the
      classical laboratory challenge.

PMID- 16610359
TI  - HSFs in development.
AB  - Heat shock transcription factors, as well as heat shock proteins, are involved in
      different steps in differentiation and development, in addition to their role in
      adaptation to stress. This has already been demonstrated in the case of the
      single heat shock factor present in Drosophila. Over the last 6 years, similar
      observations have accumulated from the progressive inactivation of the different
      hsf genes in mammals, the use of double-null animals, and the slow
      characterization of their complex phenotypes. Although these studies are not yet
      complete, the data so far can be used to draw some conclusions. All hsf genes
      contribute to development in mammals and to normal functions at the adult stage,
      by controlling the expression of Hsp and non-Hsp genes. Reproduction, the immune
      response and aging are the processes that are the most deeply affected. An
      attractive hypothesis would be that these new functions have been recruited
      during evolution in order to coordinate these processes: HSFs may occupy a
      central place in the trade off that organisms make between reproduction and
      maintenance, in response to the variations in the environment.

PMID- 16610360
TI  - Heat shock proteins: endogenous modulators of apoptotic cell death.
AB  - The highly conserved heat shock proteins (Hsps) accumulate in cells exposed to
      heat and a variety of other stressful stimuli. Hsps, that function mainly as
      molecular chaperones, allow cells to adapt to gradual changes in their
      environment and to survive in otherwise lethal conditions. The events of cell
      stress and cell death are linked and Hsps induced in response to stress appear to
      function at key regulatory points in the control of apoptosis. Hsps include anti
      apoptotic and pro-apoptotic proteins that interact with a variety of cellular
      proteins involved in apoptosis. Their expression level can determine the fate of
      the cell in response to a death stimulus, and apoptosis-inhibitory Hsps, in
      particular Hsp27 and Hsp70, may participate in carcinogenesis. This review
      summarizes the apoptosis-regulatory function of Hsps.

PMID- 16610361
TI  - Protein aggregation as a cause for disease.
AB  - The ability of proteins to fold into a defined and functional conformation is one
      of the most fundamental processes in biology. Certain conditions, however,
      initiate misfolding or unfolding of proteins. This leads to the loss of
      functional protein or it can result in a wide range of diseases. One group of
      diseases, which includes Alzheimer's, Parkinson's, Huntington's disease, and the
      transmissible spongiform encephalopathies (prion diseases), involves deposition
      of aggregated proteins. Normally, such protein aggregates are not found in
      properly functioning biological systems, because a variety of mechanisms inhibit
      their formation. Understanding the nature of these protective mechanisms together
      with the understanding of factors reducing or deactivating the natural protection
      machinery will be crucial for developing strategies to prevent and treat these
      disastrous diseases.

PMID- 16610362
TI  - The role of chaperones in Parkinson's disease and prion diseases.
AB  - The etiologies of neurodegenerative diseases, such as Alzheimer's disease,
      Parkinson's disease, polyglutamine diseases, or prion diseases may be diverse;
      however, aberrations in protein folding, processing, and/or degradation are
      common features of these entities, implying a role of quality control systems,
      such as molecular chaperones and the ubiquitin-proteasome pathway. There is
      substantial evidence for a causal role of protein misfolding in the pathogenic
      process coming from neuropathology, genetics, animal modeling, and biophysics.
      The presence of protein aggregates in all neurodegenerative diseases gave rise to
      the hypothesis that protein aggregates, be it intracellular or extracellular
      deposits, may perturb the cellular homeostasis and disintegrate neuronal function
      (Table 1). More recently, however, an increasing number of studies have indicated
      that protein aggregates are not toxic per se and might even serve a protective
      role by sequestering misfolded proteins. Specifically, experimental models of
      polyglutamine diseases, Alzheimer's disease, and Parkinson's disease revealed
      that the appearance of aggregates can be dissociated from neuronal toxicity,
      while misfolded monomers or oligomeric intermediates seem to be the toxic
      species. The unique features of molecular chaperones to assist in the folding of
      nascent proteins and to prevent stress-induced misfolding was the rationale to
      exploit their effects in different models of neurodegenerative diseases. This
      chapter concentrates on two neurodegenerative diseases, Parkinson's disease and
      prion diseases, with a special focus on protein misfolding and a possible role of
      molecular chaperones.

PMID- 16610363
TI  - Chaperoning oncogenes: Hsp90 as a target of geldanamycin.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability
      and function of a number of conditionally activated and/or expressed signaling
      proteins, as well as multiple mutated, chimeric, and/or over-expressed signaling
      proteins, that promote cancer cell growth and/or survival. Hsp90 inhibitors, by
      interacting specifically with a single molecular target, cause the inactivation,
      destabilization, and eventual degradation of Hsp90 client proteins, and they have
      shown promising anti-tumor activity in preclinical model systems. One Hsp90
      inhibitor, 17-AAG, has completed Phase I clinical trial and several Phase II
      trials of this agent are in progress. Hsp90 inhibitors are unique in that,
      although they are directed toward a specific molecular target, they
      simultaneously inhibit multiple signaling pathways that frequently interact to
      promote cancer cell survival. Further, by inhibiting nodal points in multiple
      overlapping survival pathways utilized by cancer cells, a combination of an Hsp90
      inhibitor with standard chemotherapeutic agents may dramatically increase the in
      vivo efficacy of the standard agent. Hsp90 inhibitors may circumvent the
      characteristic genetic plasticity that has allowed cancer cells to eventually
      evade the toxic effects of most molecularly targeted agents. The mechanism-based
      use of Hsp90 inhibitors, both alone and in combination with other drugs, should
      be effective toward multiple forms of cancer.

PMID- 16610364
TI  - Heat shock proteins in immunity.
AB  - This chapter focuses on immunological effects of eukaryotic and microbial heat
      shock proteins (HSPs), with molecular weights of about 60, 70, and 90 kDa. The
      search for tumor-specific antigens resulted in the identification of HSPs. They
      have been found to elicit a potent anti-cancer immune response mediated by the
      adoptive and innate immune system. Following receptor-mediated uptake of HSP
      (HSP70 and gp96) peptide complexes by antigen-presenting cells and representation
      of HSP-chaperoned peptides by MHC class I molecules, a CD8-specific T cell
      response is induced. Apart from chaperoning immunogenic peptides derived from
      tumors, bacterial and virally infected cells, they by themselves provide
      activatory signals for antigen-presenting cells and natural killer (NK) cells.
      After binding of peptide-free HSP70 to Toll-like receptors, the secretion of pro
      inflammatory cytokines is initiated by antigen-presenting cells and thus results
      in a nonspecific stimulation of the immune system. Moreover, soluble as well as
      cell membrane-bound HSP70 on tumor cells can directly activate the cytolytic and
      migratory capacity of NK cells. Apart form cancer, HSPs of different origins,
      with a molecular weight of about 60, 70, and 90 kDa, also play a pivotal role in
      viral infections, including human and simian immunodeficiency virus (HIV, SIV),
      measles, and choriomeningitis. Moreover, HSPs have been found to induce tolerance
      against autoimmune diseases. In summary, depending on their mode of induction,
      intracellular/extracellular location, cellular origin (eukaryote/prokaryote),
      peptide loading status, intracellular ADP/ATP content, concentration, and route
      of application, HSPs either exert immune activation as danger signals in cancer
      immunity and mediate protection against infectious diseases or exhibit regulatory
      activities in controlling and preventing autoimmunity.

PMID- 16610365
TI  - Molecular chaperones and cancer immunotherapy.
AB  - As one of the most abundant and evolutionally conserved intracellular proteins,
      heat shock proteins, also known as stress proteins or molecular chaperones,
      perform critical functions in maintaining cell homeostasis under physiological as
      well as stress conditions. Certain chaperones in extracellular milieu are also
      capable of modulating innate and adaptive immunity due to their ability to
      chaperone polypeptides and to interact with the host's immune system,
      particularly professional antigen-presenting cells. The immunomodulating
      properties of chaperones have been exploited for cancer immunotherapy. Clinical
      trials using chaperone-based vaccines to treat various malignancies are ongoing.

PMID- 16610366
TI  - Hsp90 inhibitors in the clinic.
AB  - Specific inhibitors of Hsp90 have recently entered human clinical trials. At the
      time of writing, trials have been initiated only in metastatic cancer, although a
      rationale exists for using these agents in a variety of human diseases where
      protein (mis)folding is involved in the disease pathophysiology. Hsp90 inhibitors
      offer a unique anti-cancer opportunity because they provide simultaneous
      combinatorial blockade of multiple oncogenic pathways. The first compound in this
      class, 17-AAG, has completed phase I trials and phase II trials are in progress.
      The toxicity has been manageable and evidence of possible clinical activity has
      been seen in metastatic melanoma, prostate cancer and multiple myeloma. Other
      inhibitors with improved properties are approaching clinical trials. This chapter
      presents an update of the current clinical trials using Hsp90 inhibitors,
      focussing on the areas that will be increasingly relevant in the next 5 years.

PMID- 16610367
TI  - Pharmacological targeting of catalyzed protein folding: the example of peptide
      bond cis/trans isomerases.
AB  - Peptide bond isomerases are involved in important physiological processes that
      can be targeted in order to treat neurodegenerative disease, cancer, diseases of
      the immune system, allergies, and many others. The folding helper enzyme class of
      Peptidyl-Prolyl-cis/trans Isomerases (PPIases) contains the three enzyme families
      of cyclophilins (Cyps), FK506 binding proteins (FKBPs), and parvulins (Pars).
      Although they are structurally unrelated, all PPIases catalyze the cis/trans
      isomerization of the peptide bond preceding the proline in a polypeptide chain.
      This process not only plays an important role in de novo protein folding, but
      also in isomerization of native proteins. The native state isomerization plays a
      role in physiological processes by influencing receptor ligand recognition or
      isomer-specific enzyme reaction or by regulating protein function by catalyzing
      the switch between native isomers differing in their activity, e.g., ion channel
      regulation. Therefore elucidating PPIase involvement in physiological processes
      and development of specific inhibitors will be a suitable attempt to design
      therapies for fatal and deadly diseases.

PMID- 16610368
TI  - Chemical chaperones: mechanisms of action and potential use.
AB  - An increasing number of studies indicate that low-molecular-weight compounds can
      help correct conformational diseases by inhibiting the aggregation or enable the
      mutant proteins to escape the quality control systems, and thus their function
      can be rescued. The small molecules were named chemical chaperones and it is
      thought that they nonselectively stabilize the mutant proteins and facilitate
      their folding. Chemical chaperones are usually osmotically active, such as DMSO,
      glycerol, or deuterated water, but other compounds, such as 4-phenylbutiric acid,
      are also members of the chemical chaperone group. More recently, compounds such
      as receptor ligands or enzyme inhibitors, which selectively recognize the mutant
      proteins, were also found to rescue conformational mutants and were termed
      pharmacological chaperones. An increasing amount of evidence suggests that the
      action of pharmacological chaperones could be generalized to a large number of
      misfolded proteins, representing new therapeutic possibilities for the treatment
      of conformational diseases. A new and exciting strategy has recently been
      developed, leading to the new chemical group called folding agonist. These small
      molecules are designed to bind proteins and thus restore their native
      conformation.

PMID- 16610369
TI  - Pharmacological modulation of the heat shock response.
AB  - Life presents a continuous series of stresses. Increasing the adaptation capacity
      of the organism is a long-term survival factor of various organisms and has
      become an attractive field of intensive therapeutic research. Induction of the
      heat shock response promotes survival after a wide variety of environmental
      stresses. Preclinical studies have proven that physiological and pharmacological
      chaperone inducers and co-inducers are an efficient therapeutic approach in
      different acute and chronic diseases. In this chapter, we summarize current
      knowledge of the current state of chaperone modulation and give a comprehensive
      list of the main drug candidates.

PMID- 16610370
TI  - Salary survey results from the Northeast Tennessee Nurse Practitioner
      Association.

PMID- 16610371
TI  - Chemtrina: direct hits, near misses, and opportunities for prevention.

PMID- 16610372
TI  - Would revival of LPN Association help Tennessee?

PMID- 16610373
TI  - How to write resolutions.

PMID- 16610374
TI  - Are surgeons accepting bribes?

PMID- 16610375
TI  - Are you being bribed? Health care ethics and compliance in the AdvaMed code era.
      Part I.

PMID- 16610376
TI  - Musculoskeletal tumor biopsy: II. Choosing the appropriate technique.

PMID- 16610377
TI  - The role of osteotomy in advanced osteonecrosis of the femoral head in sickle
      cell disease: a case report.
AB  - For young people, osteonecrosis of the femoral head (OFH) is one of the most
      debilitating complications of sickle-cell hemoglobinopathies. Management of
      advanced (Ficat and Arlet stage III or IV) OFH remains a challenging clinical
      problem: There is no ideal treatment, and management by total hip arthroplasty
      has a high failure rate. Consequently, the search continues for procedures that
      preserve the femoral head--such as vascularized and nonvascularized bone grafting
      and osteotomy. Various osteotomies have been used to try to salvage hips with
      stage II or III OFH. The Sugioka transtrochanteric rotational osteotomy is a
      technically demanding procedure with a variable success rate. Failure rates have
      also been variable for varus and valgus osteotomies after short-term follow-up.
      In this report, we present the case of a 13-year-old girl with stage III OFH
      caused by sickle-cell disease that had been successfully treated with a valgus
      flexion osteotomy of the proximal femur, with 42-month postoperative follow-up.
      We suggest that stage III OFH in a young patient with sickle-cell disease can be
      successfully treated with corrective proximal femoral osteotomy.

PMID- 16610378
TI  - Posterior sternoclavicular dislocations: a review of management and
      complications.
AB  - Posterior sternoclavicular dislocations are relatively uncommon injuries.
      Nevertheless, these dislocations are associated with potentially fatal injuries
      to the mediastinum and the great vessels. Medial clavicle physeal injury with
      posterior dislocation may present with a similar clinical picture in younger
      patients. There is a wide variety of techniques for managing these injuries. In
      this article, we review recent techniques for reducing and managing posterior
      sternoclavicular dislocations.

PMID- 16610379
TI  - Waterproof versus cotton cast liners: a randomized, prospective comparison.
AB  - Casting injured extremities can cause complications (eg, itching, odor, rashes,
      skin maceration), many of which are associated with the inability to wash the
      extremity because of water retention and slow drying of conventional cast liners.
      A waterproof cast liner allows casts to become wet and perhaps improves hygiene
      and comfort. Fifty-nine patients (age, > or = 10 years) with upper or lower
      extremity injuries were randomized to a waterproof-liner group (n = 29) or a
      cotton-liner group (n = 30). Both groups had casts made of fiberglass tape. At
      each clinic visit, patients and physicians completed questionnaires evaluating
      comfort and skin condition, respectively. The waterproof-liner group had better
      scores for itch (P = .008), discomfort (P < .001), irritation (P = .002), overall
      patient score (P = .012), and overall physician score (P = .049).

PMID- 16610380
TI  - An unusual rupture of the flexor carpi radialis tendon: a case report.
AB  - We present the unusual case of a flexor carpi radialis tendon that ruptured after
      extended strenuous physical activity by a patient with paralysis of the opposite
      limb secondary to poliomyelitis.

PMID- 16610381
TI  - Use of fluoroscopy to evaluate iliac screw position.
AB  - Iliac screw fixation is often used for long fusions to the sacropelvis. Maximum
      iliac screw purchase is obtained both by placing the screws within 1.5 cm of the
      greater sciatic notch and by extending them anterior to the axis of rotation in
      flexion-extension. Screw insertion is "blinded" or dependent on tactile feedback,
      and hence extreme care is necessary to avoid incorrect placement and damage to
      vital neurovascular structures in the pelvis and sciatic notch. Long screws may
      violate the hip joint while medial placement may injure the lumbosacral plexus
      and the nearby vessels. To explore the best intraoperative fluoroscopic method of
      determining optimal iliac screw placement, we used a synthetic pelvis model to
      investigate screw placement conditions: (1) optimal anatomic placement, (2)
      violation of the sciatic notch, (3) hip joint violation, (4) medial wall
      violation, and (5) lateral wall violation. Each condition was examined utilizing
      fluoroscopy with posteroanterior, inlet, outlet, lateral, iliac oblique, and
      obturator oblique Judet views to simulate operative conditions. These views were
      obtained to evaluate critical malposition of iliac screws. We found that, for a
      sciatic notch violation, the obturator oblique view best demonstrated the
      cortical breech, while for a hip joint violation, the inlet and outlet views were
      best. For a medial wall violation, the iliac oblique view best showed the
      violation. For a lateral wall violation, we were unable to demonstrate the
      cortical breech using these fluoroscopic views. Fluoroscopy is an effective
      method to determine sciatic notch, hip joint, and medial wall violations after
      iliac screw placement; however, it is not effective in identifying a lateral wall
      violation.

PMID- 16610382
TI  - [Message from the Pope on the World Day of the Sick].

PMID- 16610383
TI  - [Health incentives system].

PMID- 16610384
TI  - [Family system and nursing care].

PMID- 16610385
TI  - ["You shall not kill"].

PMID- 16610386
TI  - ["Love" in the maternal-fetal relation].

PMID- 16610387
TI  - [At the end death was a solution].

PMID- 16610388
TI  - [The nurse and consequences of gastric cancer].

PMID- 16610389
TI  - [Self-esteem in formal care providers and quality of life indexes in users of
      support facilities for the institutionalized elderly, in Portalegre].
AB  - It is a transversal and descriptive study, and the main meaning was to measure
      the Self-concept of formal caregivers in elderly institutions, and also the life
      quality of internally users in the same institutions. To the development of the
      study were selected two of the elderly institutions of Portalegre, Portugal. The
      population was composed by internally users (N=113) and formal caregivers (N=81)
      of both elderly institutions, being used respectively the WOHQOL-bref
      Questionnaire and the Self-concept Inventory (Vaz Serra, 1986). Based on the
      distribution of the self-concept of formal caregivers by mean point, we verify
      that 97.67% (n=42) have a high self-concept and 2.33% (n=1) have a low self
      concept. We can conclude that generally formal caregivers have a high self
      concept. About life quality value, we verify that most of internally users have
      values above the average point that identify the life quality. That suggests the
      internally users have a life quality above the medium point.

PMID- 16610390
TI  - 'Just listen to the patient'.

PMID- 16610391
TI  - Contrast-induced nephropathy.

PMID- 16610392
TI  - The optimal revascularization strategy for multivessel coronary artery disease:
      the debate continues.
AB  - Mortality rates were lower among patients with multivessel coronary artery
      disease who underwent coronary artery bypass grafting (CABG) than among similar
      patients who underwent percutaneous coronary intervention (PCI) in an analysis of
      data from New York State registries (N Engl J Med 2005; 352:2174-2183). This
      finding appears to run counter to the results of randomized controlled trials,
      which found both procedures equivalent with regard to mortality. What are we to
      believe?

PMID- 16610393
TI  - CABG or PCI? A cardiothoracic surgeon's perspective. The devil (or truth) is in
      the details.

PMID- 16610394
TI  - CABG or PCI? An interventional cardiologist's perspective. To stent or to
      operate: is this the question?

PMID- 16610396
TI  - Patient information. If you need an antidepressant...

PMID- 16610395
TI  - Side effects of antidepressants: an overview.
AB  - Adverse effects of antidepressant drugs can decrease compliance and delay
      recovery. It is therefore crucial to consider potential side effects when
      choosing an antidepressant. Although there is no perfect antidepressant that
      works quickly and is completely free of adverse reactions, newer antidepressants
      are safer, better tolerated, and associated with a lower rate of noncompliance.

PMID- 16610397
TI  - A young woman with an eroded plaque on the hand.

PMID- 16610398
TI  - A middle-aged woman with chronic liver disease and shortness of breath.

PMID- 16610399
TI  - New therapies for type 2 diabetes based on glucagon-like peptide 1.
AB  - Cells in the gastrointestinal tract secrete several hormones that stimulate
      insulin secretion, one of which is glucagon-like peptide (GLP-1). Several new
      drugs act through the GLP-1 signaling system to stimulate insulin release and
      regulate blood glucose levels in patients with diabetes. One such compound,
      exenatide (Byetta), has recently become available, and others are in clinical
      development.

PMID- 16610400
TI  - Do thiazolidinediones cause heart failure? A critical review.
AB  - Concern has been raised about whether the fluid retention caused by
      thiazolidinediones (TZDs, ie, rosiglitazone and pioglitazone) can cause or
      exacerbate congestive heart failure. Although fluid retention is a worrisome side
      effect of TZDs, current evidence does not link fluid retention caused by TZDs
      with worsening heart function. TZDs have many benefits for patients with diabetes
      and can even be used cautiously in patients with mild heart failure, with careful
      monitoring of volume status.

PMID- 16610401
TI  - Assessing the risk of surgery in patients with liver disease.
AB  - Recent studies have defined objective criteria for determining whether surgery is
      safe for patients with liver disease. Using these criteria, we may extend the
      benefit of surgery to more patients with liver disease without increasing the
      risk.

PMID- 16610402
TI  - [Family physicians must now become active. Non-compliance with vaccinations
      endangers not just the individual].

PMID- 16610403
TI  - [Travel vaccinations are often forgotten. The family practitioner as travel
      expert].

PMID- 16610404
TI  - [Therapy of ulcus cruris venosum. Not hiding chronic wounds with bandages but
      using vacuum sealing].

PMID- 16610405
TI  - [Shooting games as leisure permit. Do computer games promote violence? (interview
      by Dr. Thomas Bisswanger-Heim)].

PMID- 16610406
TI  - [A new after-care program to reinforce patient knowledge. Booster for
      cardiovascular rehabilitation].

PMID- 16610407
TI  - [The operation finally brought resolution. "Liver metastasis" was harmless].

PMID- 16610408
TI  - [Bronchitis, COPD or pneumonia? Germany on a coughing spree].

PMID- 16610409
TI  - [Acute bronchitis: when are antibiotics, and when is symptomatic treatment
      indicated?].
AB  - Acute bronchitis is usually caused by a virus, while the chronic form is due to
      inhalative noxae (in most cases decades of cigarette smoking). Both varieties are
      diagnosed on a clinical basis. Treatment of acute bronchitis is symptomatic. A
      sore throat is treated locally, and a troublesome, in particular nocturnal, cough
      with antitussive agents applied for a limited period (14 days). If bronchial
      mucus is viscous and difficult to clear, short-term treatment with a secretolytic
      or mucolytic substance is justified. Management of chronic bronchitis consists
      primarily in the elimination of the noxae. Treatment with antibiotics (usually
      oral) makes good sense only when there is a bacteriological infection of the
      upper or lower airways in an acute stage, such as infection-driven exacerbation
      of chronic obstructive bronchitis (COPD).

PMID- 16610410
TI  - [COPD--how to deal with an acute exacerbation].
AB  - Exacerbations in COPD patients are characterized by an acute aggravation of the
      condition with an increase in symptoms (labored breathing, cough, expectoration,
      tightness of the chest and, rarely, fever). The major cause is a bronchial
      infection. The medications of choice are inhalative bronchodilators, in
      particular beta-2 sympathomimetics and/or anticholinergic agents, together with
      systemic glucocorticosteroids, and also theophylline. COPD patients experiencing
      exacerbations and showing clinical signs of bacterial airway infection can
      benefit from antibiotic treatment. In the presence of an acute partial
      respiratory insufficiency, administration of oxygen is indicated, while
      respiratory insufficiency with hypercapnea and acidosis necessitates the use of
      noninvasive positive pressure ventilation. For the prevention of acute
      exacerbations, risk factors must be eliminated, in particular cigarette smoking.
      Furthermore, optimized management including structured patient education is to be
      recommended.

PMID- 16610411
TI  - [Management of community-acquired pneumonia in the physician's office].
AB  - The classical form of a community-acquired pneumonia is that caused by infection
      with pneumococcus, and differs clinically from atypical pneumonia in particular
      by fever-related differences. The diagnosis is based on the five cardinal
      symptoms: fever, cough, sputum production, pleuritic chest pain and a pulmonary
      infiltrate. Depending on whether there are further risk factors involved, a more
      or less comprehensive clinical and laboratory diagnostic work-up is needed. As a
      rule, oral antibiotic treatment with aminopenicillin, macrolides,
      fluorchinolones, ketolides or cephalosporins is applied, but decision-taking is
      also codetermined, for example, by whether an atypical pneumonia is suspected, or
      whether additional risk factors need to be taken into account.

PMID- 16610412
TI  - [Gender-specific hypertensive treatment].

PMID- 16610413
TI  - [Ocular manisfestations of systemic disease].
AB  - In many cases, patients with systemic diseases may present with a variety of
      ocular manifestations. The most common of these are "red eye" or a visual
      disturbance."Red eye" may be the first symptom of a condition from the group of
      rheumatic diseases and urgently mandates an ophthalmological investigation.
      Visual disorders occur, for example, in an underlying diabetic condition or
      arterial hypertension. Patients with arterial hypertension and/or diabetics must
      consult an ophthalmologist at regular intervals. Not only the underlying disease
      itself, but also its treatment can give rise to ocular complications. Patients on
      certain drugs - such as chloroquine or ethambutol should be referred for an
      ophthalmological examination at regular intervals.

PMID- 16610414
TI  - [Erroneous opinions refuted. New knowledge about an old effective substance].

PMID- 16610415
TI  - [Is anti-hyperalgesia clinically relevant? Dosage increase is hardly necessary].

PMID- 16610416
TI  - [Not just in the East: progressively shorter lengths of stay for patients.
      Clinics save, family physicians sigh].

PMID- 16610417
TI  - [Setting up private practice shortly after the political change. Our children
      went along to the house call].

PMID- 16610418
TI  - [New S3 guideline for therapy of bacterial respiratory tract infections.
      Renaissance of tetracyclines].

PMID- 16610419
TI  - [Oxytetracycline + myrtol standardized in sinusitis and bronchitis. General
      practice test passed with "very good"].

PMID- 16610420
TI  - [Oh, pine tree].

PMID- 16610421
TI  - Preimplantation genetic diagnosis.
AB  - Preimplantation genetic diagnosis (PGD) is an early form of prenatal diagnosis
      whereby embryos obtained in vitro are tested for the presence of a certain
      genetic disease. Patients who are at risk to have a child with a genetic disease
      can thus avoid a prenatal diagnosis and a possible termination of pregnancy. At
      the Centres for Medical Genetics and Reproductive Medicine, we have applied PGD
      for monogenic diseases since 1993 and are now one of the largest in the world. In
      this paper, the theoretical and technical side of PGD will first be explained.
      Thereafter, our activity since 1993 will be described. At the end of 2004, we had
      carried out 713 cycles for 319 patients for 54 different indications, leading to
      159 (22 %) clinical pregnancies. The ESHRE PGD Consortium, of which I am
      chairperson, has been collating data on PGD from PGD centres from the whole
      world. This has led to the publication of four reports that are considered widely
      as important documents, as well as a comprehensive set of guidelines. Finally,
      there is the aspect of the scientific research ensuing from the PGD programme.
      The research into the causes of instability of triplet repeats in genetic
      diseases such as DM1 and Huntington's disease has made significant progress. The
      embryonic stem cell lab was started up in 2002, and has already succeeded in
      deriving five new lines, as well as progressing significantly into the research
      in differentiation to muscle cells and the behaviour of triplet repeats in
      totipotent stem cells.

PMID- 16610422
TI  - [The nutrition situation of young children in Flanders].
AB  - Knowledge of the present feeding habits and the impact of different information
      channels are mandatory for developing an appropriate feeding policy. The" Socio
      Economisch Instituut (SEIN)", the "Universiteit Hasselt", and paediatricians of
      the Virga Jesse Hospital conducted a study on the feeding habits of young
      children between the age of 0 and 2 years in Flanders. This study was ordered by
      Kind en Gezin. Special attention was paid to breastfeeding. The study uses
      qualitative and quantitative methods. The qualitative research is limited to
      questions about breastfeeding such as which factors influence initiating,
      maintaining and ending breastfeeding. The quantitative research investigates
      through diaries the dietary composition, the eating habits and the parental
      educational support. Parents of young children aged 3, 6, 12 and 24 months
      throughout Flanders were questioned. The response rate was 71%, resulting in 2925
      diaries that were analyzed. The study gives a comprehensive profile of the
      dietary habits of young children in the Flanders. Overall, feeding habits in
      these young infants seem to be appropriate. Concrete proposals to promote
      breastfeeding and to further improve healthy feeding habits in this age group are
      made.

PMID- 16610424
TI  - Fiscal dangers lurking in the Deficit Reduction Act.

PMID- 16610423
TI  - [A review of the nutritional management plans in the member states of the
      European Union].
AB  - Obesity has reached epidemiological proportions in Europe and the burden of
      diseases attributable to nutrition is substantial. Under the impetus of the World
      Health Organisation (WHO), member states have been urged to develop national
      action plans for nutrition and physical activity. This study describes what has
      been done in terms of nutrition policy at national level in the member states of
      the European Union right before its enlargement in 2004. It is a critical review
      of publicly available policy documents on nutrition and physical activity. The
      background idea was to assist the initiative of the Belgian food industry to play
      a proactive role in the development of a Belgian nutrition action plan. At the
      time of writing, in total six out of the fifteen EU member states namely Sweden,
      Finland, Denmark, France, the Netherlands and the United Kingdom, reported to
      have an operational national nutrition plan. By the end of the year 2004, another
      four countries are expected to have their plan finalised. In line with WHO
      guidelines, all nutrition plans in this study acknowledge the importance of a
      multidisciplinary approach and promote stakeholder involvement at some point.
      Most of the plans however, do not elaborate on their specific role and strategies
      that will be used to do so. It seems that stakeholder mobilisation is largely
      restricted to the implementation phases. All operational nutrition plans envisage
      reducing social disparities. Long-established vulnerable groups in society such
      as pregnant women, children and elderly are targeted. Considerable variability
      was observed for nutritional objectives and dietary recommendations between the
      different countries. Nutrition surveillance and monitoring activities seem to
      vary considerably between the different action plans. None of the countries
      except Denmark documents the theoretical foundations and development process of
      their nutritional surveillance system. National nutrition policy in Europe is
      clearly in a state of flux and the centre of gravity seems to move away from
      Scandinavia. Although the importance of nutritional surveillance, comprehensive
      approach to nutritional problems and stakeholder involvement is recognised by the
      action plans, the rationale, justification and mechanisms for it is vaguely
      described. Our findings call for increased efforts to strengthen the evidence
      base of public health nutrition policy. To achieve this however, systematic
      evaluations and proper reporting of which health and nutrition promotion
      strategies work in the different countries in the EU are urgently needed.

PMID- 16610425
TI  - Fred Lee: thinking like Disney.

PMID- 16610426
TI  - The State of the Union speech and health care.

PMID- 16610427
TI  - Going for the gold by turning 'green'.

PMID- 16610428
TI  - Controlling implant costs.

PMID- 16610429
TI  - The case for an owner's representative.
AB  - Hospitals can retain an outside owner's representative to manage a building
      project. To prepare for the selection process, hospitals should consider the
      nature of the building project and of the organization. For a successful project,
      hospitals need to clarify roles, manage expectations, and make decisions.

PMID- 16610430
TI  - How clean are your bills?
AB  - An audit of the UB-92 should address the following questions: Are all current
      procedural terminology codes assigned by health information management
      transferred to the bill? Are all services and medications being correctly
      captured? Are services being "double charged" by departments that do not
      understand the complexity of the billing process? Are all CPT codes in the
      chargemaster appearing on the claims?

PMID- 16610431
TI  - Finding the balance between quality and cost.
AB  - The key to controlling healthcare costs and increasing value lies in a balance
      among three key aims developed by Japanese quality expert Noriaki Kano:
      Eliminating quality problems that arise because the expectations of consumers are
      not met Reducing costs significantly while maintaining or improving quality
      Expanding the expectations of consumers by providing products and services that
      they perceive as unusually high in value.

PMID- 16610432
TI  - Eyes on the supplies: results of a massive performance improvement initiative.
AB  - The University of Utah Hospitals & Clinics learned three lessons from its
      performance improvement initiative: Develop and track key performance indicators
      and compare them with performance targets on a monthly basis. Identify and define
      core processes and subprocesses, and build an appropriate organizational
      structure to support those processes. Identify supply cost-savings opportunities
      by focusing first on procurement.

PMID- 16610433
TI  - Revenue cycle outsourcing: the real costs and benefits.
AB  - Hospitals need to consider the real financial and human costs and benefits of
      outsourcing before making an outsourcing decision. Hospitals should ensure that
      selected outsourcing contractors can meet their objectives. Hospitals need to
      have a contingency plan in place in case an outsourcing firm fails to meet
      expectations.

PMID- 16610434
TI  - Easing the bottom-line impact of staffing shortages: a case study in shift
      bidding.
AB  - Among the potential financial advantages of online shift scheduling and bidding
      are: Decreased agency use; Improved employee recruitment and retention; Reduced
      administrative time spent scheduling; Improved staffing practices to leverage
      existing workforce.

PMID- 16610435
TI  - The beginning: a good place to start for healthcare reform.
AB  - The healthcare continuum can be divided into stages that move from cause to
      effect. Each stage is a potential place to focus on improving the management of
      our healthcare system. The key is to make proactive care profitable for providers
      without making it too expensive for all other affected stakeholders.

PMID- 16610436
TI  - Margin alert: time to revisit your outpatient strategy.
AB  - An increasingly competitive market for outpatient services has made it necessary
      for acute care hospitals to reevaluate their outpatient, and inpatient,
      strategies. Many acute care hospitals are in a strong market position to command
      premium payment for their inpatient services. Under current market conditions,
      hospitals are in danger of pricing themselves out of the outpatient market.
      Hospitals can benefit from the increased focus of consumers and payers on quality
      and the rise of pay for performance by investing in service excellence.

PMID- 16610437
TI  - Financial A/R policy: Preservice and time-of-service processing.

PMID- 16610438
TI  - Poor management can look like discrimination.

PMID- 16610439
TI  - What is IT architecture?

PMID- 16610440
TI  - Why oncology business development?

PMID- 16610441
TI  - Northeast shows higher-than-average Medicare allowances for hospital admissions.

PMID- 16610443
TI  - And a postscript.

PMID- 16610442
TI  - Non-urine body fluid specific gravity.

PMID- 16610445
TI  - The progression of allergic disease.

PMID- 16610444
TI  - Specific IgE testing: Objective laboratory evidence supports allergy diagnosis
      and treatment.

PMID- 16610446
TI  - Pharmacogenomics: The relevance of emerging genotyping technologies.

PMID- 16610447
TI  - What's in that pot o'gold?

PMID- 16610448
TI  - A medical lab career in the U.S. Army: challenges with rewards.

PMID- 16610449
TI  - Privacy and surveillance cameras in the workplace.

PMID- 16610450
TI  - Middleware: What's the buzz?

PMID- 16610451
TI  - Update on the laboratory workforce-shortage crisis.

PMID- 16610452
TI  - Preventing misconnections of lines and cables.
AB  - The hospital environment is filled with lines and cables connecting medical
      devices with patients. With so many connections to be made, it's not surprising
      that, occasionally, one of them will be incorrect. Often, such mistakes are
      caught before harm is done. But when they aren't, patients can be harmed or even
      killed. There are two basic ways in which hospitals can reduce the likelihood of
      misconnections, and they should be applied together. First, whenever possible,
      hospitals should purchase equipment whose design makes a misconnection unlikely
      or prompts users to make the correct connection. Second, hospitals should
      implement general policies and specific work practices that keep misconnections
      to a minimum. In concert with these efforts, hospitals should conduct a risk
      assessment to identify specific misconnection hazards within the facility. This
      article describes the specific steps hospitals should take to tackle
      misconnections. It also pinpoints the more important misconnection scenarios to
      look for during a risk assessment. And it includes a checklist that will
      facilitate not only the risk assessment but also the overall misconnection
      prevention endeavor.

PMID- 16610453
TI  - Purchasing a decentralized medication management system.
AB  - Decentralized medication management systems (DMMSs) are used in hospitals, long
      term care facilities, prisons, outpatient clinics, surgery centers, and other
      places to manage the distribution of drugs. DMMSs consist of storage compartments
      for medications, with an internal computer that controls and records the
      administration of drugs. Some DMMSs are stationary cabinets and others are mobile
      carts. There have been important advances in DMMS technology since we evaluated
      these products in 1996, including enhanced computer memory and processing power,
      wider adoption of wireless networking, better user interfaces, and greater
      integration with other hospital information systems. To get the most out of a
      DMMS purchase or upgrade, facilities will need careful planning that involves
      assessing their own needs, selecting hardware and software configurations that
      meet those needs, and then choosing the right vendor and model. A properly
      selected DMMS can help to enforce medication distribution policies, prevent
      errors, and streamline processes.

PMID- 16610454
TI  - Hazard report. Always check image magnification when using nucletron's plato
      14.2.5 brachytherapy planning system.

PMID- 16610456
TI  - User experience network. Needle problems: breaking, coring, and detaching.

PMID- 16610455
TI  - Talk to the specialist. When should conductive casters be used?

PMID- 16610457
TI  - Coronal leakage of calcium phosphate-based root canal sealers compared with usual
      sealers.
AB  - The purpose of the present study was to compare two experimental calcium
      phosphate-based sealers with AH Plus, Sealapex, Ketac-Endo and Hermetic with
      regard to coronal seal. Two standardized artificial canals were prepared in each
      of 120 blocks of bovine root dentin. The blocks were divided into six groups. All
      of the 40 canals of each group were filled with gutta-percha and either AH Plus,
      Hermetic, Ketac-Endo, Sealapex or two different experimental sealers. One canal
      of one block was filled with gutta-percha and sealer using lateral condensation,
      whilst the other canal was obturated using Thermafil. The roots were immersed in
      black ink and thereafter cleared. Maximum linear dye penetration was measured
      coronally. Statistical analysis was performed by means of the Kruskal-Wallis test
      for the global null hypothesis and the closed test procedure for pairwise
      comparisons. With lateral condensation, experimental sealer I was comparable with
      AH Plus and Hermetic but showed significantly higher penetration depths than
      Ketac-Endo and Sealapex. Using Thermafil, more leakage was found for experimental
      sealer I than for AH Plus, Ketac-Endo and Sealapex. Using both techniques,
      leakage of experimental sealer II did not differ significantly from leakage of AH
      Plus, Ketac-Endo and Sealapex. Due to the low leakage of experimental sealer II
      in the present study, further evaluations such as bacterial penetration or fluid
      filtration should follow.

PMID- 16610458
TI  - [Survey of treatment-seeking complete denture wearers concerning tooth loss,
      retention behavior and treatment expectations].
AB  - The aim of the current study was to gather information about time and etiology of
      tooth loss, and to analyze the reasons for treatment needs with a questionnaire
      used among edentulous patients. 60 patients (age 44-98 years) who requested
      dental treatment were included. More than half of the patients were edentulous
      before the age of 60, in almost all cases the maxilla was affected first. This
      difference was more pronounced in women, who experienced tooth loss in the
      maxilla 17 years prior to the mandible. At the time of edentulism women were
      about ten years younger than men. According to patients'report, periodontal
      disease was the most common reason for tooth loss. In the mandible, prosthesis
      retention was influenced by alveolar ridge resorption, while in the maxilla there
      was no relation between the amount of resorption and perceived retention. This
      indicates that maxillary prostheses retention is influenced by other factors
      besides the alveolar ridge morphology. So, permanent intake of drugs potentially
      causing xerostomia was related to poorer assessment of prostheses retention in
      the upper jaw. The results of the questionnaire "Patient satisfaction related to
      prosthetic restoration" before treatment indicated that the general satisfaction
      with the existing complete denture in the mandible was influenced by functional
      problems and the impairment of patients'self-confidence (R-squared = 0.754). The
      main reason for requesting treatment was the poor retention of the lower denture.
      More than half of the participants stated that they refrained from eating certain
      foods due to a reduced chewing ability.

PMID- 16610459
TI  - [Patient satisfaction with removable implant-supported prostheses in the
      edentulous mandible].
AB  - The aim of the present study was to investigate patients' satisfaction with
      removable implant restorations with two or four implants compared to a complete
      denture (CD) in the edentulous mandible. 20 patients in each group were asked to
      fill out a questionnaire ("Patient satisfaction related to the prosthetic
      restoration") before treatment, after six months and three years. With implant
      restorations, either implant-retained (IRET) or implant-supported (ISUP), greater
      improvements in prostheses retention and pain reduction were achieved in
      comparison to complete dentures. In addition, restrictions related to food
      selection were resolved for most implant patients. Despite great inter-individual
      differences, there was a tendency for larger improvements of almost all
      parameters with IRET, except chewing ability, which was rated best with ISUP.
      Long-term results revealed that patients with ISUP (four implants) assessed
      prostheses retention with the highest ratings compared to those with IRET and CD
      (p = 0,0147). These results indicate that an improvement in functional and
      psychological parameters can be achieved with two implants, whilst stabilization
      with four implants improves prosthesis retention, chewing ability and pain
      reduction in the long term. Maintenance efforts were more complex for implant
      restorations than for CD and imply a recall at least once a year.

PMID- 16610460
TI  - [External root resorption].
AB  - Root resorption may be a physiological (resorption of deciduous teeth) or a
      pathological process (resorption of permanent teeth). In the latter case an
      external and an internal form of resorption can be distinguished. Root resorption
      may occur on one tooth or on several teeth within a dentition and it may be
      caused by trauma, periodontitis, orthodontic treatment, internal bleaching,
      cysts, tumors, or by stimuli from a necrotic dental pulp. Current knowledge
      concerning the pathogenesis of root resorption and therapeutic approaches are
      presented. For cervical resorption, it is assumed that the stimulus for the
      resorbing cells originates from the bacteria within the gingival sulcus and along
      the affected root surface. The case presented here was initially diagnosed as
      chronic periodontitis of medium severity. Scaling and root planing were performed
      resulting in a significant improvement of the periodontal status. Two years
      later, following a period of irregular recall visits, the patient presented with
      large areas of cervical resorption on teeth 36 and 37 which made it impossible to
      preserve these teeth. After another six months, teeth 34 and 35 showed deep
      destruction caused by external root resorption, mandating the extraction of these
      teeth as well. Fourteen months later, external root resorptions were evident on
      teeth 32 and 33, and at the same time, a recurrence of the chronic periodontitis
      was noted. Periodontal therapy was performed under a systemic antibiotic regime.
      It was possible to preserve teeth 32 and 33 through surgical crown lengthening
      procedures. No additional resorption has been observed ever since.

PMID- 16610461
TI  - [The SPI implant system: clinical experience and one-year results].
AB  - The new Swiss implant system SPI became available three years ago and is used in
      combination with fixed and removable prosthetic reconstructions. In a pilot study
      the clinical procedures were evaluated and data of prosthetic complications of
      maintenance service were collected. 25 patients participated in the study with a
      total of 79 SPI implants during the time period from 2003-2004. 37 implants were
      located in the maxilla and 42 implants in the mandible. Two implants failed
      during the healing period, but no loaded implant was lost. Thus, the survival
      rate was 97.5% (77/79). 44 implants supported a fixed prosthesis, including nine
      single crowns and 33 implants were used in combination with removable partial
      denture. Four implants were used with ball anchor retention, 29 with bar support.
      The ELEMENT implant with the low implant shoulder allows very good esthetics.
      Prosthetic complications and maintenance service during the first year of
      function was comparable with other implant systems. Since the design of the
      abutment screws, healing caps and screwdriver was changed, the system has become
      easier in its application.

PMID- 16610462
TI  - [Anterior teeth esthetics with the SPI implant system].
AB  - Replacement of maxillary front teeth with a fixed, implant supported partial
      denture with a high laugh line is a demanding procedure. For an optimal esthetic
      result, no deficiency of bone or soft tissue is acceptable. Submerged implant
      healing has often been recommended for better predictability in esthetically
      demanding situations. This case report shows the rehabilitation with a fixed
      implant supported reconstruction in the upper front and a single implant
      supported crown in the premolar region. Teeth had to be extracted because of
      apical lesions, periodontal the gingiva. The technique of delayed, submerged
      implant placement in the region of 11, 21 and 22 was applied and in the region of
      15 a transmucosal implant healing. With a fixed, implant supported partial
      denture the mucosa in the upper front was conditioned. Ten months after
      implantation the definitive screwed, fixed partial denture on SPI ELEMENT
      implants was successfully integrated. In the region 15 a single crown
      transversally screwed was fixed on a SPI ONE TIME implant. Radiographic data two
      years after implantation showed a well established periimplant crestal bone
      level. No prosthetic complications had occurred since the insertion of the
      reconstruction twelve months ago.

PMID- 16610463
TI  - Common CYP450 drug interactions with psychiatric medicines: A brief review for
      the primary care physician.
AB  - With thousands of drug interactions possible, it is next to impossible to
      remember them all. Additionally, with the common use of psychiatric medicines in
      primary care practice, drug interactions may occur without recognition. Some drug
      interactions are negligible while other drug interactions are quite significant.
      It is most important to remember the drug interactions that can have a clinical
      effect. Since approximately half of all medications prescribed today are affected
      by P450 enzymes, it is important to recognize some important interactions. This
      brief review will address the most common medications used to treat psychiatric
      illnesses today and their potential to cause CYP450-mediated drug interactions.

PMID- 16610464
TI  - The state of South Dakota's child: 2005.
AB  - In 2004, the total number of births increased again in South Dakota with the
      percent of minority births 21.3%) surpassing the national rate (21.1%). The
      national trend of increasing rates of low birth weight is also noted in South
      Dakota. Though the state's rates of low birth weight (<2500 grams) and very low
      birth weight (<1500 grams) are lower than national rates, they have reached their
      highest level since an unusual peak in 1974. In 2004, 1.23% of all newborns
      weighed less than 1500 grams and nearly 7% had a birth weight of less than 2500
      grams. In 2004, the state's infant mortality rate increased by 24% over the
      previous year to 8.2 per 1000 live births, exceeding the national rate of 7.0.
      The South Dakota increase is entirely accounted for by increases in the white
      neonatal (less than 28 day) mortality rate. Analyses of these observations
      suggest that an increase in deaths due to congenital anomalies and perinatal
      causes may be associated with white neonatal loss. Deaths due to Sudden Infant
      Death Syndrome have decreased and are now more closely approaching national
      rates.

PMID- 16610465
TI  - Follow-up systems: why doctors need to care.

PMID- 16610466
TI  - Byetta (exenatide): what's your gut feeling?

PMID- 16610467
TI  - Pneumococcal vaccination guidelines.

PMID- 16610468
TI  - Preparing for pandemic influenza--what you can do.

PMID- 16610469
TI  - A doctor's story.

PMID- 16610470
TI  - South Dakota State Medical Association's advocacy agenda.

PMID- 16610471
TI  - Education of the deaf and General Motors.

PMID- 16610472
TI  - Behavior change in a student with a dual diagnosis of deafness and pervasive
      developmental disorder: a case study.
AB  - The broad term pervasive developmental disorder (PPD) describes a set of symptoms
      that occur along a continuum of severity; these symptoms are often referred to as
      autism spectrum disorders (ASDs). Little is known about the incidence and
      prevalence of ASDs among students who are deaf or hard of hearing (DHH). Teachers
      of DHH students, who must work with individuals with dual diagnoses, are at a
      loss for guidance from the literature. The authors review the literature on ASDs
      (also referred to as PDD) within the DHH population, provide results of a single
      subject study to reduce PDD-type behaviors in a child with hearing loss, and
      argue that teachers of students who are DHH must learn about practices associated
      with applied behavior analysis as an tool for intervening therapeutically with
      children with dual diagnoses of hearing loss plus an ASD.

PMID- 16610473
TI  - Deaf clients' perceptions of counseling expertise as a function of counselors'
      signing skill, gender, and therapy type.
AB  - The study examined deaf clients' perceptions of counseling expertise as a
      function of several counseling variables: counselor's signing skill, gender, and
      therapy type. Twenty undergraduate students at a special college for the deaf who
      were enrolled in either counseling courses or psychology courses viewed 4 video
      clips reflecting a mock counseling session. After viewing the clips, the
      participants were asked to complete the Counselor Rating Form--Short Form
      (Corrigan & Schmidt, 1983). There was no statistically significant main effect
      for the sex of the counselor, the match between the counselor's gender and the
      client's gender, or the mode of communication. While the study demonstrates the
      utility of the method for future research with deaf clients, further
      modifications of the method are necessary.

PMID- 16610474
TI  - Education of the deaf in Australia and Norway: a comparative study of the
      interpretations and applications of inclusion.
AB  - Inclusion is a term and process that is culturally, politically, medically,
      philosophically, and historically relative in its interpretations in the
      education of the deaf. The present study is a comparative analysis of two
      substantially different education systems for deaf students, those of Norway and
      Australia. The study objective was to elucidate the sources of some of these
      differences and to examine the interpretations and applications of inclusion that
      are inherent in the two countries' policies and practices, and in recent research
      evaluations. Significant differences exist in the national contexts and in the
      manner in which inclusion is understood and applied in Norway and Australia; the
      study reports on recent research examinations of inclusion in the two countries
      and finds that the transitions from policy to practice seem questionable.

PMID- 16610475
TI  - The effect of multimedia stories about American deaf celebrities on Taiwanese
      hearing students' attitudes toward job opportunities for the deaf.
AB  - In Taiwan, hearing people generally think deaf individuals can only do jobs
      requiring minimal communication. The present study was planned to help change
      hearing people's attitudes toward deaf people's job competence. Multimedia
      stories of deaf celebrities, e.g., physicians, lawyers, university presidents,
      professors, senior government officials, and movie stars, were developed. A
      multimedia computer reading program was developed in which graphic organizers,
      picture clues, video, and voice were integrated to make reading more exciting and
      pleasant. Materials were developed to be suitable for dissemination on CD.
      Regarding attitude change, all differences between pretests and posttests were
      statistically significant: Hearing students' attitudes toward deaf and hard of
      hearing people changed positively and significantly. It is recommended that the
      CD featuring American deaf celebrities be distributed to make hearing people
      understand deaf people's potential, and to contribute to an environment conducive
      to their employment in Taiwan.

PMID- 16610476
TI  - Administrators' ratings of competencies needed to prepare preservice teachers for
      oral deaf education programs.
AB  - Deaf education teacher preparation programs must prepare teachers to staff an
      increasing number of oral programs. A survey was conducted to determine which
      competencies administrators of deaf education programs rate as important for
      teachers in oral programs and to compare ratings of these competencies by oral
      school administrators to ratings made by administrators of comprehensive deaf and
      hard of hearing programs. Between the two groups of administrators, six areas of
      agreement about competencies were found. There were notable differences in the
      range of ratings between the two groups. These differences were attributed to the
      roles teachers assume in the two types of programs and the focus of instruction
      in each type of program.

PMID- 16610477
TI  - An examination of the evidence-based literacy research in deaf education.
AB  - The ability to read and write for a variety of purposes is essential to success
      in school and in contemporary society. The purpose of this investigation was to
      conduct an exhaustive review of the literature and a meta-analysis of literacy
      research in the field of deaf education. Computer and manual searches of 40 years
      of peer-reviewed journal articles were conducted. A total of 964 articles related
      to literacy and deafness were identified and examined; 22 articles met the
      criteria for inclusion in the review. Results indicate that (a) no two studies
      examined the same dimension of literacy; (b) there was a paucity of well-designed
      group studies; (c) there were no systematic replication of studies; (d) there is
      limited data to establish evidenced-based practices. Consequently, increasing the
      quantity and improving the quality of research in the field is recommended.

PMID- 16610478
TI  - Deaf education in China: history, current issues, and emerging deaf voices.
AB  - An overview is provided of (a) deaf education in China, (b) views of deaf
      Chinese, and (c) recent empowering international collaborations. China's national
      policy focuses on oral/aural education and hearing rehabilitation. However,
      everyday practice in schools for deaf children includes various forms of Chinese
      Sign Language. Early childhood education focuses on speech and hearing.
      Elementary and secondary school curricula reflect low expectations for deaf
      students and lack the same academic content provided to hearing students. There
      are limited higher education opportunities. There are no support services such as
      note takers or interpreters for mainstreamed students. There are no deaf teacher
      preparation or interpreter training programs. Jobs are few; the vast majority of
      deaf adults are unemployed. Deaf people interviewed for the article describe
      their needs, their dreams, and the changes they are witnessing, which result in
      part from recent empowering international collaborations.

PMID- 16610479
TI  - Views from the field: program directors' perceptions of teacher education and the
      education of students who are deaf or hard of hearing.
AB  - Arandom sample of directors of programs for the deaf in North America were
      surveyed to get their views about the skills that teacher education programs need
      to be teaching future teachers of students who are deaf or hard of hearing. The
      directors were queried about literacy practices, classroom management strategies,
      and communication strategies used in their programs, and were encouraged to
      comment freely on the questionnaire items presented to them. Program directors
      predicted a need for more itinerant and resource teachers. The survey also
      revealed that programs for the deaf are highly behaviorist (i.e., You do this and
      you'll get that) in the way they induce students to learn and in how they manage
      student behavior.

PMID- 16610480
TI  - Writing for publication: supporting the neonatal nurse practitioner student.
AB  - Our ultimate goal with this manuscript preparation course is twofold. First, our
      purpose is to encourage nurses to examine and apply the published evidence
      available on a selected clinical topic in the hopes that this will be
      incorporated into a pattern of lifelong learning for the individual. Second, this
      process encourages students to share their knowledge with other professionals,
      thereby advancing the scientific knowledge available for nursing practice. These
      are key components of the advanced practice nursing role and graduate students
      need mentoring during their education to be successful in the future. Students
      (and faculty!) find this course challenging but rewarding and the vast majority
      of students end up with a published manuscript. Although not all students
      appreciate the challenges, the majority of students are proud of what they have
      accomplished despite the intense amount of work. Final comments from several
      students include: I was never more proud of the work you made me accomplish." "I
      can't believe it is done! How exciting." "Thank you so much for all of your help
      and guidance. This has been a rewarding experience to see the progression of the
      manuscript...." "I did find this course to be challenging to say the least!" "I
      can honestly say that this semester was one of the most challenging, but most
      rewarding projects that I have done so far in grad school. And yes, I promise
      never to use secondary sources and give credit to authors in the rest of my
      work!"

PMID- 16610481
TI  - Steps to successfully breastfeed the premature infant.
AB  - The birth of a premature infant causes emotional upheaval for parents. They often
      wonder what they can do to help their infant during the critical newborn period.
      Providing breast milk is one of the most important physiologic benefits a mother
      can give her premature infant. The advantages of breast milk are numerous. It is
      the responsibility of those who care for premature infants and their families to
      provide parents with the support they need to supply the best possible nutrition
      for their infant. Breastfeeding a premature infant can challenge both the mother
      and her health care team, however. Infants should be assessed individually for
      readiness to proceed through the steps leading to successftil breastfeeding. From
      establishing a milk supply to putting the baby to the breast, parents rely on the
      nurse for information, instruction, and encouragement. This article identifies
      obstacles to breastfeeding the premature infant and offers a step-by-step
      approach for promoting successful breastfeeding in the NICU.

PMID- 16610482
TI  - Sturge-Weber syndrome: A case study.
AB  - Sturge-Weber syndrome (SWS) is a rare, sporadic, progressive, congenital
      syndrome. In its complete trisymptomatic form, SWS is physically characterized by
      port-wine stains over the trigeminal area, leptomeningeal angiomas usually over
      the parieto-occipital region, and eye abnormalities. Clinical manifestation for
      infants with SWS depends on the affected organs, but can include seizures, mental
      retardation, and glaucoma. This article begins with a case presentation of an
      infant with SWS and then presents the etiology, embryology, pathophysiology,
      clinical presentation, management, and prognosis of SWS.

PMID- 16610483
TI  - Cloacal exstrophy.
AB  - Cloacal exstrophy is an extremely rare and devastating complex of congenital
      abnormalities resulting in multiple debilitating morbidities. Infants with this
      disorder require numerous surgical interventions to repair gastrointestinal,
      genitourinary, spinal, and orthopedic malformations. Treatment involves the
      combined efforts of many medical and nursing specialists. This article discusses
      the embryology, clinical presentation, and management (both early and long term)
      of cloacal exstrophy, with emphasis on gender reassignment issues and quality of
      life.

PMID- 16610484
TI  - Car seat safety for high-risk infants.
AB  - Most neonates discharged from the hospital are able to go home in a standard car
      safety seat. Some infants, though, require special devices to ensure their safe
      travel. NICU nurses must have the knowledge and skills to comfortably and
      competently give vital information to parents preparing to take their infant
      home. This article is intended to increase awareness among NICU nurses of the
      potential dangers babies face when placed in a car seat. It provides a basic
      overview of car seat safety for infants being discharged home from an NICU and
      includes references for those who seek further information on this topic.

PMID- 16610485
TI  - NRP 2006: What you should know.
AB  - In spring 2006, the American Academy of Pediatrics (AAP) and the American Heart
      Association (AHA) will introduce revised materials for the Neonatal Resuscitation
      Program (NRP). These revisions affect the practice of neonatal resuscitation as
      well as the administrative components of the NRP. This article cannot address
      every program revision. Instead, it summarizes what prompted the program changes
      and then introduces the reader to guideline revisions that affect practice, as
      well as to changes in NRP tools and resources. The fifth edition of the Textbook
      of Neonatal Resuscitation is currently in press. The AAP granted permission to
      use material from the forthcoming edition in this article.

PMID- 16610486
TI  - What's happening with career planning?

PMID- 16610487
TI  - [The award winners explain (part 2)].

PMID- 16610488
TI  - [Can a virtual community maintain the exercise of nursing in family medicine
      groups?].

PMID- 16610489
TI  - [Should we immunize health personnel, students and their professors?].

PMID- 16610490
TI  - [Nosocomial infections. Education is the order of the day].

PMID- 16610491
TI  - [Evaluating thoracic pain in triage].

PMID- 16610492
TI  - [When convincing results equal excellence in practice].

PMID- 16610493
TI  - [The nurse's role in an research ethics committee].

PMID- 16610494
TI  - [Diagnosis and treatment of HIV-related Kaposi's sarcoma].
AB  - A 42-year-old heterosexual man presented with bluish-purple spots on his skin and
      in his mouth cavity that had been present for a few months; a 48-year-old
      homosexual man had painful lymphadenopathy in the groins and left axilla. Both
      men appeared to have a Kaposi's sarcoma and to be HIV-positive. During highly
      active antiretroviral therapy (HAART) and radiotherapy or chemotherapy, both the
      AIDS parameters and the skin lesions improved. Kaposi's sarcoma is AIDS-defining
      in HIV-seropositive patients. Human herpesvirus-8 infection seems to play a role
      in the development of Kaposi's sarcoma. The incidence of Kaposi's sarcoma has
      declined since the introduction of HAART. Nowadays, Kaposi's sarcoma is
      frequently the presenting symptom of HIV-seropositivity. Patients present with
      purple cutaneous lesions and/or generalised lymphadenopathy. Visceral lesions are
      associated with a shorter median survival. The treatment of Kaposi's sarcoma is
      palliative, whereas immune restitution can lead to regression of the sarcoma.

PMID- 16610495
TI  - [Death due to or despite the doctor].
AB  - In the last week of life, the extent and kind of medical practice differ both in
      intention and in the degree of orientation on the outcome. Patients tend to put
      long-term prescriptions aside or ask for symptom-relieving medication and
      sometimes for palliative sedation, euthanasia or physician-assisted suicide.
      Competent physicians are able to offer or withhold treatment. In case of
      unconsciousness or severe cognitive impairment, proxies may ask for medical
      relief of disturbing symptoms. Medical practice is subject to the Dutch Medical
      Treatment Act (1995). At the start of the specific Dutch law specifying judicial
      review of euthanasia and physician-assisted suicide (1993, implemented in 2002)
      1.8% of deaths concerned euthanasia. In 2005, standard drugs (choice, dose and
      route of administration) were highly effective in all cases of euthanasia in
      which they were used (76%): death within a median of 3-4 min, maximum 90 min. In
      the absence of medical indications for drug overdose, morphine and other choices
      are now considered obsolete for euthanasia and physician-assisted suicide. The
      definition of euthanasia must be based exclusively on a standard method and
      outcome: death on request by a standard medical method with a standard judicial
      review.

PMID- 16610496
TI  - [Screening of asymptomatic individuals for coronary disease using CT-calcium
      measurement in the coronary arteries].
AB  - Coronary calcification is a specific marker for coronary atherosclerosis. It is
      therefore reasonable to assume that the risk ofcardiac events can be assessed by
      the quantification of the extent of coronary calcium. Until now, the predictive
      value of coronary calcium and its advantage over conventional risk factors has
      not been proven by any of the available prospective cohort studies. It is
      particularly likely that assessment of coronary atherosclerosis will help in the
      decision to initiate or discard a specific therapy in patients with an
      intermediate risk for cardiac events. Recently it has been suggested that the
      Framingham risk score (FRS) be replaced by a score corrected by assessing the
      amount of coronary calcium, which can be obtained by multislice spiral computed
      tomography (MSCT). To this end, the Commission Law Population Investigation has
      approved a study proposal to evaluate the effects of coronary-calcium screening
      in 4000 asymptomatic individuals with an intermediate likelihood of coronary
      artery disease. Based on the amount of calcium (calcium score > 100) obtained by
      MSCT, different treatment strategies will be initiated over a period of 5 years.
      Hard endpoints will be myocardial infarction, stroke and mortality due to
      cardiovascular disease.

PMID- 16610497
TI  - [The use of complementary and alternative medicine in children: how to advise the
      parents?].
AB  - Recently it has been shown that complementary or alternative medicine (CAM) is
      used in about 30% of paediatric patients. Is this a problem? It has also been
      shown that most parents would like their paediatrician to advise them on the
      subject. But what can be the basis of such advice? Little is known and less has
      been published regarding the effectiveness of CAM. Society and the medical
      profession are notoriously ambiguous on the subject. Sound scientific evidence is
      advocated to make bold decisions on whether to allow and reimburse the use of
      CAM.

PMID- 16610498
TI  - [New policy regarding the number of authors included with articles in the
      Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine)].
AB  - The editors of this journal have decided that the number of authors of original
      articles and guidelines may in the future exceed the current limit of six. For
      other articles, e.g. clinical lessons, case reports and review articles, the
      limit remains. Contributions to the series 'Diagnostic image' will have a maximum
      of two authors. For a number of years now, authors have been asked to provide
      specific information as to the nature of their contribution to the article that
      carries their name. This enables the editors and the reviewers to assess whether
      the criteria for authorship have been met. Information on authors' contributions
      will not be printed alongside the articles but will be kept available to readers
      for three months after the article has appeared.

PMID- 16610499
TI  - [Spaander, Director-General for the Institute of Public Health, 1950-1979].

PMID- 16610501
TI  - [Vasectomy: indications and implementation in historic perspective].
AB  - Approximately 35,000 vasectomies were performed in the Netherlands in 2004.
      Although vasectomy may be looked upon as the most reliable method of
      contraception (risk of pregnancy in the first year: 0.08-0.15%), realistic
      preoperative counselling about possible complications such as haemorrhage (5%),
      wound infection (5%), and haematoma (14%) and long-term consequences such as the
      wish for renewed fertility (2.6% of the men opt for vasectomy reversal), the
      delayed achievement of sterility (4% three months after vasectomy), chronic
      scrotalgia (5%) and the risk of recanalisation (0.28-00.5%) is of utmost
      importance. Moreover, the couple should be convinced that vasectomy can only be
      considered successful if less than 100,000 non-motile sperms per ml are
      demonstrated by a certified laboratory in a post-vasectomy semen analysis. As an
      alternative for vasectomy, several clinical studies to assess the value of male
      hormonal contraception are currently in progress.

PMID- 16610500
TI  - [Exertion-related abnormalities in the urine].
AB  - Strenuous exercise can lead to the occurrence of various abnormalities in the
      urine. Hematuria and proteinuria are those most frequently described. Other less
      common possibilities are pigmenturia like hemoglobinuria and myoglobinuria. These
      urine abnormalities are found not only in sportsmen/women or soldiers, but also
      in percussionists. Other possible causes are hereditary metabolic myopathy and
      the use of drugs or medication. Exertion-related urine abnormalities occur
      frequently and are usually benign. Any abnormalities should disappear after a
      period of 24-72 h of rest. Exertional rhabdomyolysis only appears 24-48 h after
      exercise. This condition rarely leads to acute renal failure and the need for
      (temporary) renal replacement therapy. When exertion-related urine abnormalities
      do not disappear spontaneously following a period of rest, further investigation
      as to the cause, e.g. renal or urological disease, should be started. Prevention
      of exertion-related urine abnormalities is possible by ensuring an adequate fluid
      intake during and following exertion.

PMID- 16610502
TI  - [Diagnostic image (266). A woman with a non-healing wound on the chin].
AB  - A 67-year-old woman presented with a non-healing spot on the right side of her
      chin, which was caused by a dental fistula arising from a periapical granuloma of
      the right lower second premolar.

PMID- 16610503
TI  - [No prior informed consent required for 'no-risk' scientific research].
AB  - Recent research has shown that prior informed consent not only leads to a lower
      response but also distorts the results of the study. The concern about the
      protection of the individual may not be given preference over the importance of
      participation in a study, in particular for those studies that carry a very
      limited or non-existent risk or that are not burdensome to the patient.

PMID- 16610504
TI  - [Prior informed consent is also a requirement of 'no-risk' scientific research].
AB  - The right to decide for oneself about participation in medical research is the
      foundation of informed consent. If the requirement of informed consent is dropped
      for research that is considered free of risk to the individual participant, then
      participation becomes involuntary. The absence of risk is an insufficient
      argument to ignore an individual's right to free choice.

PMID- 16610505
TI  - [Trends in the agents used for euthanasia and the relationship with the number of
      notifications].
AB  - OBJECTIVE: To provide insight into the relationship between the drugs used for
      euthanasia and its notification. DESIGN: Retrospective and descriptive. METHODS:
      By comparing the drugs used for euthanasia according to different components of
      studies carried out in 1990, 1995 and 2000, insight was obtained into the drugs
      used in all cases of euthanasia satisfying the definition thereof (death
      certificate studies), those cases of euthanasia that, in addition, were defined
      as such by the physician (physician interviews), and the cases of euthanasia
      that, in addition, had been reported (reported case studies). RESULTS: In 2001,
      standard drugs for euthanasia were used in 76% of cases and opioids in 23%.
      Euthanasia with standard drugs was reported in 73% of cases in 1995, and in 71%
      of cases in 2000, while euthanasia with opioids was reported in 2% and 1% of
      cases, respectively. The total percentage of euthanasia reported was higher in
      2001 than in 1995 (54% versus 44%), since in 2001 euthanasia was apparently
      performed more often with standard drugs and less with opioids. CONCLUSION: An
      increasing proportion of cases of euthanasia is being carried out with the drugs
      recommended for this purpose. Euthanasia with opioids was rarely reported.
      Possibly, physicians did not always consider these cases to be euthanasia.

PMID- 16610506
TI  - [The use of complementary and alternative medicine in children at a general
      paediatric clinic and parental reasons for use].
AB  - OBJECTIVE: To determine the prevalence of and reasons for the use of
      complementary and alternative medicine (CAM) in paediatric patients, and to
      determine the parental need for appropriate information from their paediatrician.
      DESIGN: Questionnaire. METHOD: A questionnaire was given to the parents of
      general paediatric patients of the St. Antonius Hospital Nieuwegein and the
      University Medical Centre Utrecht, the Netherlands, in the period June 2003-March
      2004. Parents were asked about CAM use in the past 12 months, which CAM
      modalities were used and their reasons for using it. They were also asked about
      their need to receive information on CAM from their paediatrician. RESULTS: A
      total of 581 of 617 parents completed the questionnaire (94%). CAM was used by
      177 (30%) patients. The most frequently used types of CAM were homeopathy (48%),
      phytotherapy (45%), nutritional supplements (28%) and manual therapies (28%). CAM
      was used most often in children with headache or chronic fatigue. The most
      frequently cited reasons for CAM use were a desire for the child to feel better
      and a preference for a 'more natural' therapy. Factors associated with CAM use
      were a high level of parental education and use of CAM by the parent. Only 40% of
      parents had reported the use of CAM to their paediatrician, usually on their own
      initiative. The majority of the parents (60%) found it important to very
      important that the paediatrician is able to provide information on CAM.
      CONCLUSION: Almost one-third of patients visiting a general paediatrician had
      used complementary or alternative medicine in the past year. Given the possible
      interactions with conventional therapies and the desire of parents to receive
      more information on CAM, paediatricians should expand the patient history
      assessment to include questions regarding the use of CAM.

PMID- 16610507
TI  - [Episodes of angioedema in children with C1 esterase inhibitor deficiency].
AB  - A 6-year-old boy and a 3.5-year-old girl presented with unexplained episodes of
      angioedema without urticaria. Low serum C1 esterase inhibitor activity was found
      in both children. Family history revealed autosomal dominant inheritance in the
      girl. The boy had a negative family history for angioedema. C1 esterase inhibitor
      deficiency is a rare but serious condition that may cause oedema of the upper
      respiratory tract and death by asphyxiation. Episodes of angioedema occur
      spontaneously, usually subsiding within 48-72 h. Between episodes, the patients
      are symptom free. Treatment consists of substitution of synthetic C1 esterase
      inhibitor during episodes of edema carrying a risk of upper airway obstruction.
      In patients who have more than one episode of severe angioedema per month, daily
      treatment with tranexamic acid should be considered. Both of these patients were
      not receiving daily treatment.

PMID- 16610508
TI  - [A single nighttime trauma helicopter does not represent a significant
      improvement in emergency assistance].
AB  - The medical benefits of nighttime missions by one single helicopter emergency
      medical service for trauma patients in the Netherlands are probably outweighed by
      the high risk for the crew and the general obstacles to nighttime flight
      operations. It is doubtful whether one nighttime trauma helicopter will have a
      favourable effect on the morbidity and mortality due to major trauma in the
      Netherlands. However, extending the role of regional centres in pre-hospital
      emergency medicine could be an approach to achieving long-term improvements in
      trauma care.

PMID- 16610509
TI  - [Severe psychosis in an African woman due to the antiretroviral agent efavirenz].

PMID- 16610510
TI  - [Severe psychosis in an African woman due to the antiretroviral agent efavirenz].

PMID- 16610511
TI  - ['Gold standard,' not 'golden standard'].

PMID- 16610512
TI  - [Probabilities cannot be calculated retrospectively--not even in the courtroom].

PMID- 16610513
TI  - [The significance of elevated troponin levels in the absence of acute cardiac
      ischaemia].

PMID- 16610514
TI  - [The first patient with the new variant of Creutzfeldt-Jakob's disease in The
      Netherlands].

PMID- 16610515
TI  - [Thumb hypoplasia].
AB  - All the components of the thumb can be involved in congenital hypoplasia.
      Blauth's classification continues to be helpful for description of the degree of
      hypoplasia leading to different options of surgical reconstruction. Surgical
      strategy includes first web deepening, MP ligamentoplasty, thenar augmentation
      using tendon transfer and correction of associated abnormalities involving the
      extensor and flexor tendons. For grade IIIB and grade IV, recommended option for
      reconstruction is index finger pollicisation.

PMID- 16610516
TI  - [Subungual glomus tumors of the fingers: ultrasound diagnosis].
AB  - INTRODUCTION: Glomus tumors of the fingers are rare, benign tumors. These lesions
      are hamartomas, originating from dermoepidermic glomus, most commonly located at
      the distal phalanx, and in particular under the nail. Diagnosis is often delayed
      because of the absence of specific symptoms. Confirmation can only be made by
      histological study. The aim of this retrospective study is to define the role of
      ultrasound examination in the diagnosis of glomus tumors of the fingers. METHOD:
      During the period March 2002-March 2004, 12 cases of subungueal glomus tumors
      were included in this retrospective study. All patients underwent ultrasound and
      Doppler examinations before surgery. All Ultrasound Doppler studies were
      performed by the same radiologist. The mean age of patients was 44 year-old and
      the sex-ratio was 1/2. RESULTS: Pain was noted as a symptom in all patients. The
      mean size of the tumor was 3.5 mm. In eleven patients, ultrasound study was able
      to confirm the diagnosis, but it failed in one case because of the small size of
      the tumor (less than 2 mm). Ten tumors presented a Doppler hypersignal, located
      in the tumor and compatible with the diagnosis of glomus tumor. DISCUSSION:
      Diagnosis of glomus tumor is based on clinical examination, standard radiology,
      and ultrasound Doppler study. Ultrasound examination and Doppler study gives
      better visualization of tumors compared to standard radiology. These studies are
      useful for follow-up of patients in the post-operative period.

PMID- 16610517
TI  - [Merkel cell carcinoma of the skin: two case reports located at the hand, with a
      review of litterature].
AB  - The Merkel cell carcinoma of the skin are rare neuroendocrine tumours, with a
      dermal location. Their severity and metastatic potential are higher than
      cutaneous melanomas'. Two cases are reported at the hand. A review of literature
      displays the pejorative prognosis of these tumours. Hand surgeons must be aware
      of them, in order to fasten the diagnosis and include the patient among a
      multidisciplinary medical team.

PMID- 16610518
TI  - [Treatment of dorsally displaced distal radius fractures with a double dorsal
      plate: a study of 12 patients].
AB  - BACKGROUND: Distal radius fractures with dorsal displacement and comminution are
      unstable and difficult to treat. Several surgical techniques have been suggested.
      Dorsal plates may have some advantages because of the failure of external
      fixation and pinning. The biomechanical superiority of radius reconstruction
      using two dorsal plates in both radial columns has been demonstrated in
      comparison to other techniques. METHODS: A prospective study was made on 12
      patients with distal radius fractures with dorsal displacement, operated with
      double Mathys plates used in neutralization, and seven cases were grafted with
      Endobon. RESULTS: We have a follow-up of ten months. According to the Herzberg
      score, one case was rated as excellent, seven as good, three as medium and one as
      bad. The average flexion was 48.3 degrees, extension 49.8 degrees, pronation 75
      degrees and supination 80 degrees. We found two cases of algodystrophy, and one
      of malunion. DISCUSSION: The best indication to apply the double dorsal plates on
      distal radius fractures is for metaphyso-diaphyseal fractures with dorsal
      displacement, comminution and articular involvement. Among its advantages,
      plating allows good control of the articular surface and of the "posterior
      middle" fragment. A stable and solid ostheosynthesis allows rapid re-education
      and mobilization.

PMID- 16610519
TI  - [Digital lengthening by gradual distraction].
AB  - The authors report their experience of digital lengthening and analyze the
      indications and results of 12 cases performed over 13 years in the plastic and
      reconstructive surgery service of the Kassab institute. Distraction was performed
      using a mini-orthofix device. In majority of cases, the procedure was performed
      on young people, manual workers and victims of industrial accidents. The
      lengthened osseous segment was the 1st metacarpal in 7 cases, the proximal
      phalanx of the index in 3 cases, the 3rd metacarpal once and the proximal phalanx
      of the middle finger in one case. Gradual distraction at the rate of 0.25 to 0.5
      mm/day was carried out in 10 cases using the procedure of "callotasis". In 2
      cases the distraction was performed at a rate of 1 mm/day followed by bone graft.
      Callotasis allowed us to obtain an average lengthening of 17 mm (61.5%) in
      distraction of the phalanx, and 26 mm (63.3%) in distraction of the first
      metacarpal. This technique avoids the spontaneous shortening observed after the
      use of bone graft alone. Complications are relatively frequent but had little
      influence on the final result.

PMID- 16610520
TI  - [Chondrosarcoma of the hand].
AB  - The authors report 5 cases of chondrosarcoma of the hand brought together over a
      period of 20 years. The series comprises 3 men and 2 woman of average age 42
      years. In two cases the tumour arose from degeneration in a preexisting lesion of
      Ollier's disease. Diagnosis was made on clinical and radiological criteria.
      Confirmation of the diagnosis by histological examination proved to be difficult
      in 2 cases. The treatment was surgical, with ray amputation in 3 cases and
      curettage with bone graft in the other 2. None of the patients had a recurrence
      at 4.5 years mean follow-up.

PMID- 16610521
TI  - [Incidence and causes of failures in wrist arthroscopic techniques].
AB  - OBJECTIVES: Arthroscopy represents a new and promising technique for the
      diagnosis and treatment of disorders of the wrist. Causes predis posing to
      clinical failure can arise during any phase of the approach to a patient who is a
      candidate for arthroscopic treatment. The author examine the causes of failure
      during pre-operative diagnostic workup, operative procedure and post-operative
      rehabilitation program and discus how to prevent them. MATERIALS AND METHODS:
      Three hundred fifty outpatients who had wrist arthroscopy were reviewed to
      determine type of procedure, type of anaesthetic, portals used and incidence and
      nature of preoperative, operative, and postoperative complications. Complications
      were divided in two groups: major and minor. The first group consists of isolated
      or combined vascular, nerve and/or tendon injuries, compartment syndrome joint
      infection and RSD, wrist rigidity. The second group includes transient
      superficial dorsal ulnar sensory neurapraxia, superficial portal sit infection,
      skin burns, tendonitis, instrumentation breaking inside the wrist joint, ganglion
      formation, haematomas. In a separate group othe causes of failure, especially
      those due to surgical or rehabilitation failures, are considered. RESULTS: Ten
      cases of surgical and post-surgical complications (2,9%) and 8 other cases of
      failure considered separately (2,3%) were identified, making a total of 18 cases
      of clinical failure (5,1%). Among these complications 4 cases were classified as
      "major" [sensory nerve branch lesions of ulnar nerve (3 cases) and of radial
      nerve (1 case)] and 6 cases were classified as "minor" [sensory neurapraxia (3
      cases), instrumentation breakage (1 case), ganglion formation (1 case), a large
      subcutaneous haematoma (1 case)]. CONCLUSIONS: Wrist arthroscopy is a
      sophisticated procedure, requiring dedicated surgical training and a thorough
      knowledge of joint disorders in order to lower the risks of complications and
      surgical failures.

PMID- 16610522
TI  - [The floating forearm: elbow and perilunate dislocation].
AB  - To the five cases published in the literature concerning concomitant elbow and
      perilunate dislocation, the authors add a sixth case and discuss the
      epidemiologic, clinical and therapeutic characteristics of this complex injury.

PMID- 16610523
TI  - [Traumatic ulnar nerve dislocation (a case report and literature review)].
AB  - The authors report a case of post-traumatic ulnar nerve dislocation at the elbow
      and, having reviewed the literature, they discuss the pathogenesis, diagnosis and
      management of this injury.

PMID- 16610524
TI  - Sectoral network on occupational health and safety in agriculture to support
      enterprises and family farms in Estonia.
AB  - A sectoral network on occupational health and safety in agriculture has been
      established in Estonia as part of a project that provided support for Estonian
      accession into European Union. Participating organizations represent farmers'
      unions at county level, agricultural enterprises, workers' representatives,
      universities and agricultural expert institutions, and government agencies. The
      purpose is to provide a shared infrastructure that combines information and other
      capacities of several organizations and provides a platform for dialogue and co
      operation in order to make a greater impact with available resources. The network
      has a decentralized architecture and is technically managed by an
      institutionalized secretariat. The network's task forces have compiled a network
      directory, summarised the capacities and interests of member organizations, made
      an inventory of existing information and training materials, developed an overall
      strategy for information management, established an information repository on the
      Internet, prepared promotional materials, and devised a protocol for agricultural
      walk-though assessment. A profile on occupational health and safety in Estonian
      agriculture has been compiled with a rapid assessment approach that collected
      both quantitative and qualitative information from secondary sources (statistics,
      documents) and from focus group discussions. The profile is used as an instrument
      for taking occupational health and safety needs in agriculture into discussion on
      political arena.

PMID- 16610525
TI  - A review of the literature on preventive occupational health and safety
      activities in small enterprises.
AB  - The scientific literature regarding preventive occupational health and safety
      activities in small enterprises has been reviewed in order to identify effective
      preventive approaches and to develop a future research strategy. During the last
      couple of years, there has been a significant increase in the number of studies
      of small enterprises, but the research community is scattered between many
      different disciplines and institutions. There is a lack of evaluation of
      intervention studies, both in terms of effect and practical applicability.
      However, there is sufficiently strong evidence to conclude that employees of
      small enterprises are subject to higher risks than the employees of larger ones,
      and that small enterprises have difficulties in controlling risk. The most
      effective preventive approaches seem to be simple and low cost solutions,
      disseminated through personal contact. It is important to develop future
      intervention research strategies which study the complete intervention system:
      from the intermediaries through dissemination methods to the resulting preventive
      activities of the small enterprises.

PMID- 16610526
TI  - Activities and ways of organizing better occupational health and safety in small
      workplaces: special focus on information.
AB  - Information is needed in all activities aiming at the development and improvement
      of working conditions. The information and communication technology has made it
      possible to have information available 24 h a day, 360 d a year. The
      administrative structures in various countries also call for more information
      steering at the workplace level. This means that more web-based and other
      materials for small enterprises are needed in all countries in order to improve
      safety and health of the workers. Four different approaches to improve workplace
      level activities are described here to provide models for others to modify them
      to their local conditions. The networking of small workplaces supports the
      development of their safety and thereby also their productivity and possibilities
      to offer jobs also in the future.

PMID- 16610527
TI  - Approaches to occupational health based on participatory methodology in small
      workplaces.
AB  - An intervention based on the methodology developed by the International Labour
      Office, the Work Improvement in Small Enterprises (WISE) was carried out to
      improve work condition of small-scale enterprises and the informal sector in the
      Philippines, Thailand and Japan. Through the evaluation of the efficacy of the
      approaches based on participatory methodology, it is concluded that the method is
      an efficient measure to improve work condition in small workplaces. It is also
      pointed out that the activities of supporting experts such as introduction of the
      methodology and evaluation of the activity are necessary. The important roles of
      the experts are 1) to encourage managers and workers to sustain the activities
      for work improvement, 2) to analyse the effectiveness and problems of the
      implemented improvements, 3) to give appropriate suggestions for the further
      improvement, and 4) to get materials for demonstrating the effectiveness of WISE
      activities on improving work conditions and productivity to other managers and
      workers who have not participated in the activity.

PMID- 16610528
TI  - Total approach is a must for small and medium enterprises to attain sustainable
      working conditions and environment, with special reference to Bali, Indonesia.
AB  - Attention and assistance to enhance the role of small and medium scale
      enterprises (SMEs) by the government is more emphasized due to the success of
      SMEs in earning significant amount of foreign currency when Indonesia had to face
      economical crisis in 1997. This policy has been highly recognized again since the
      bombing tragedy in 2002; with the excellent evidence to show how important SMEs
      is in helping and maintaining the economic development of Bali. But in the
      implementation the assistance needs to be remanaged again in a more proper and
      appropriate way to attain the ultimate goals. The three economic potentials,
      agriculture in broad sense, tourism and SMEs (cottage industry included), must be
      developed in harmony, interdependence, support and complementary each other, if
      possible as synergist to obtain sustainable development of Bali. While assistance
      to SMEs must be done in a more coordinated way among the government technical
      offices, universities, NGOs, banking, and other social community institutions. By
      doing so, there would be no duplication or gap, nor creation of new
      disadvantageous problems. It could be in form of ergonomics, occupational health
      and safety impacts and problems in particular, and in adverse working conditions
      and environment in general. Therefore it is a must at this moment to carry out
      total approach in helping SMEs, by integrating the effort to improve their
      working conditions and environment, built-in within the effort to enhance
      SMEs'quality of life through economic assistance. In this process a total
      approach through SHIP approach and Appropriate Technology intervention must be
      done wisely and timely. By so doing, SMEs'sustainable working conditions and
      environment shall be attained.

PMID- 16610529
TI  - Exposure assessment in SMES: a low-cost approach to bring OHS services to small
      scale enterprises.
AB  - There is increased attention to improving occupational health and safety in small
      to medium-sized Enterprises (SMEs). The Workers Health Centre, a not-for-profit
      OHS service in western Sydney, assessed workplace exposures in two SMEs following
      intervention by regulatory agencies. A low-cost monitoring program for noise,
      airbone dust, fibers and chemicals was conducted at these two metal working
      industry workplaces. Results showed that exposure to the hazards were above the
      statutory limits and there was generally an unhealthy access to OHS information
      by the predominantly immigrant or low literate worker population, were
      identified. The potential for using a program of low-cost exposure assessments,
      accompanied by a strategy to provide OHSs information for workers in small-scale
      enterprises, is discussed.

PMID- 16610530
TI  - Advances in participatory occupational health aimed at good practices in small
      enterprises and the informal sector.
AB  - Participatory programmes for occupational risk reduction are gaining importance
      particularly in small workplaces in both industrially developing and developed
      countries. To discuss the types of effective support, participatory steps
      commonly seen in our "work improvement-Asia" network are reviewed. The review
      covered training programmes for small enterprises, farmers, home workers and
      trade union members. Participatory steps commonly focusing on low-cost good
      practices locally achieved have led to concrete improvements in multiple
      technical areas including materials handling, workstation ergonomics, physical
      environment and work organization. These steps take advantage of positive
      features of small workplaces in two distinct ways. First, local key persons are
      ready to accept local good practices conveyed through personal, informal
      approaches. Second, workers and farmers are capable of understanding technical
      problems affecting routine work and taking flexible actions leading to solving
      them. This process is facilitated by the use of locally adjusted training tools
      such as local good examples, action checklists and group work methods. It is
      suggested that participatory occupational health programmes can work in small
      workplaces when they utilize low-cost good practices in a flexible manner.
      Networking of these positive experiences is essential.

PMID- 16610531
TI  - Development of multi-dimensional action checklist for promoting new approaches in
      participatory occupational safety and health in small and medium-sized
      enterprises.
AB  - To meet diversified health needs in workplaces, especially in developed
      countries, occupational safety and health (OSH) activities should be extended.
      The objective of this study is to develop a new multi-dimensional action
      checklist that can support employers and workers in understanding a wide range of
      OSH activities and to promote participation in OSH in small and medium-sized
      enterprises (SMEs). The general structure of and specific items in the new action
      checklist were discussed in a focus group meeting with OSH specialists based upon
      the results of a literature review and our previous interviews with company
      employers and workers. To assure practicality and validity, several sessions were
      held to elicit the opinions of company members and, as a result, modifications
      were made. The new multi-dimensional action checklist was finally formulated
      consisting of 6 core areas, 9 technical areas, and 61 essential items. Each item
      was linked to a suitable section in the information guidebook that we developed
      concomitantly with the action checklist. Combined usage of the action checklist
      with the information guidebook would provide easily comprehended information and
      practical support. Intervention studies using this newly developed action
      checklist will clarify the effectiveness of the new approach to OSH in SMEs.

PMID- 16610532
TI  - Networking grassroots efforts to improve safety and health in informal economy
      workplaces in Asia.
AB  - Many workers in Asia are in the informal economy. They often work in substandard
      conditions, exposed to hazards in the workplace. Learning from the recent
      successes of participatory training programmes to improve safety and health in
      Asia, the ILO has strengthened its partnership efforts with local people to
      improve safety and health of informal economy workplaces. The target groups were:
      (1) home workplaces in Cambodia and Thailand, (2) salt fields and fishing
      villages in Cambodia where many young workers are working, and (3) small
      construction sites in Cambodia, Laos, Mongolia, Thailand and Vietnam. The walk
      through survey results showed that the workers and owners in the target informal
      economy workplaces had the strong will to improve safety and health at their own
      initiatives and needed practical support. In the participatory, action-oriented
      training workshops carried out, the participated workers and owners were able to
      identify their priority safety and health actions. Commonly identified were clear
      and safe transport ways, safer handling of hazardous substances, basic welfare
      needs such as drinking water and sanitary toilets, and work posture. The follow
      up visits confirmed that many of the proposed actions were actually taken by
      using low-cost available materials. These positive changes were possible by
      applying the participatory training tools such as illustrated checklists and
      extensive use of photographs showing local good examples and placing emphasis on
      facilitator roles of trainers. In conclusion, the target informal economy
      workplaces in Asia made positive changes in safety and health through the
      participatory, action-oriented training focusing on local initiative and low-cost
      improvement measures. Local network support mechanisms to share lessons from good
      practices played essential roles in encouraging the voluntary implementation of
      practical improvement actions. It is important to increase our joint efforts to
      reach more informal economy workplaces in industrially developing countries and
      provide practical support measures focusing on local self-help initiatives.

PMID- 16610533
TI  - Control of hazardous substances at small workplaces.
AB  - Lots of chemicals are produced in chemical industry and used everywhere as
      convenient and indispensable materials in daily life and industry. Moreover, many
      new chemicals are needed to produce competitive new goods such as new medicines,
      new dyestuffs, new agricultural chemicals and others. Main chemicals used in
      industry have reached to more than 50,000 kinds. And many workers are exposed to
      chemicals and injured all over the world. To protect the workers in small
      workplaces against hazardous chemicals is one of the most important tasks of
      occupational health. n-Hexane, lead and 1-bromopropane poisoning are shown as
      examples for health hazards and preventive measures in small workplaces.
      Preventive measure such as TLV or OEL, Material Safety Data sheets, health check
      up, comprehensive cooperation among employers, workers, researchers, industrial
      physicians and administrative officers, and information on toxicity are
      discussed.

PMID- 16610534
TI  - A case study on evaluations of improvements implemented by WISE projects in the
      Philippines.
AB  - The aim of this study is to evaluate the effects of work improvements in small
      enterprises (WISE) on workloads and productivity, and managers' satisfaction with
      those projects. Participating in this study from 1994 to 1996 were 9 small
      enterprises, 3 metal industries, 1 car parts manufacturing, 1 garment
      manufacturing, 1 food processing, and a few others. Upon visiting these
      worksites, we carried out interviews on the implemented WISE improvements and
      made objective evaluations of their effect on workloads and productivity.
      Reductions in physical workloads were found in 4 of 6 enterprises where that
      factor was estimated. Productivity in most of the enterprises increased after
      WISE improvements. Managers' subjective satisfaction with WISE activity ranged
      between 50-80% on each technical item. More than 50 percent of managers came to
      understand the necessity of workers' involvement and understanding of the
      activities in order to sustain activity for improvement. WISE activity can exert
      a beneficial influence on workload and productivity. Most of the managers were
      satisfied with the results. It is presumed that follow-up visits with objective
      estimation will provide both managers and workers with encouragement to maintain
      their efforts.

PMID- 16610535
TI  - The characterization of airborne occupational safety and health hazards in
      selected small businesses; manufacturing wood pallets.
AB  - Researchers from the National Institute for Occupational Safety and Health
      (NIOSH) investigated occupational safety and health concerns in the small
      business wood pallet manufacturing industry because of an injury rate (2000) 226%
      greater than that for general industry. NIOSH investigators conducted walk
      through evaluations at seven wood pallet manufacturing companies, and returned to
      four of them to take environmental measurements. Carbon monoxide (CO) levels,
      noise levels, and total particulate were measured, ergonomic observations made,
      and occupational safety practices analyzed at each of the four facilities where
      measurements were taken. The focus of this study is the evaluation of airborne
      particulate and carbon monoxide exposures for the purpose of determining areas of
      potentially high exposures. This knowledge can guide the plant owner or health
      professional to determine whether further measurements are necessary and where
      they might be needed. Safety factors and physical stressors (noise and ergonomic
      stressors) were described in a previously published companion paper. Although we
      did not take 8 h samples, we did find certain exposures that were potentially of
      concern to the small business owner. The main findings of this investigation were
      as follows: 1) CO levels in three plants, for the time periods measured, were
      less than the OSHA permissible exposure limit (PEL) of 50 parts per million (ppm)
      for an 8-h TWA. Three measurements, all from one plant, were due to a older and
      defective forklift and were above 50 ppm. 2) Total dust measures ranged from 0.86
      to 1.67 mg/m3, taken adjacent to an operating machine cutting hardwood and
      measured up to 6 min. The American Conference of Governmental Industrial
      Hygienists (ACGIH) guideline for hardwood dust is 1.0 mg/m3, again for an 8-h
      TWA.

PMID- 16610536
TI  - Health effects of occupational exposure to fluorine and its compounds in a small
      scale enterprise.
AB  - A 7-yr study was conducted to evaluate the respiratory effects of fluorine
      compounds on exposed workers in a small-scale enamel enterprise. Air monitoring
      was done and 75 pairs, exposed and non-exposed workers were examined. The applied
      tests were: an epidemiological questionnaire, the bronchitis record, clinical
      examinations and urinary fluorine. Linear regression analysis was done. The
      values of fluorine in the air of workplaces ranged from 0.1 to 3.7 mg/m3 air
      during the study. Twenty five point and seven percent of exposed workers
      presented chronic rhinitis, laryngotracheitis and bronchitis. The smoking habit
      was similar in both groups. The incidence of chronic bronchitis was significantly
      higher in exposed workers compared to the non-exposed ones. The values of urinary
      fluorine were higher in the exposed versus the control group. Linear regression
      analysis has shown positive correlations between the fluorine exposure and
      incidence of chronic bronchitis (r=0.75), as well as the incidence of chronic
      respiratory diseases (r=0.71). Fluorine exposure may be responsible for the high
      incidence of chronic irritative respiratory diseases, especially for chronic
      bronchitis in exposed workers. For diseases prevention it is advisable to reduce
      the levels of fluorine in the air of workplaces and to decrease the concentration
      of fluorine compounds in the composition of enamel.

PMID- 16610537
TI  - Retrospective cohort study of cancer mortality at the Minsk Leather Tannery.
AB  - The cohort of 768 workers who were actively employed for a minimum of 6 months
      and died was retrospectively followed from 1 January 1953 to 31 December 2000.
      There were 328 women and 440 men observed. Proportionate mortality ratios (PMRs)
      were calculated using the Minsk-city population mortality proportions to generate
      expected numbers. The significant excess of pancreatic cancer (PMR=366%;
      95%CI=134-800) and melanoma and skin cancer (PMR=455%; 95% CI=123-1,164) in women
      workers of Dyeing and stuffing workshops was shown. The significantly high
      mortality from pancreatic cancer among Dyeing and stuffing workshops' female
      workers hired and discharged between 1958 and 1984 (PMR=1,024%; 95% CI=11-2,109),
      melanoma and skin cancer (PMR=440%; 95% CI=240-2,327) among Dyeing and stuffing
      workshops female workers who started before 1970, lip and buccal cavity among men
      who began working within 1974-1978 (PMR=1,071%; 95% CI=220-3,128), cervix and
      corpus uteri cancer among workers employed before l960 was found. It should be
      noted that the significantly high mortality from above noted cancers was
      indicated for Dyeing and stuffing workshops female workers with seniority more
      than 10 yr. Thus it was shown for pancreatic cancer (PMR=418%; 95% CI=136-975),
      for melanoma and skin cancers (PMR=497%; 95% CI=102-1,450), for uterus cancers
      (PMR=269%; 95% CI=130-496).

PMID- 16610538
TI  - Selecting high-risk micro-scale enterprises using a qualitative risk assessment
      method.
AB  - Micro-scale enterprises (MSEs) with less than 5 employees are subject to be
      covered by the scheme of the regular workplace environmental inspection and
      medical health examination from 2002 in Korea. Due to limited resources as well
      as vast number of enterprises to be covered, there is an urgent need to focus
      these efforts to only those high-risk MSEs. To identify them, a qualitative risk
      assessment methodology was developed combining the hazardous nature of chemicals
      and exposure potentials as modeled by the HSE and the risk categorization
      technique by the AIHA. Risk Index (RI) was determined by combining
      characteristics specific to chemicals and scale of use of the chemicals. The
      method was applied to 514 MSEs that were selected from a random sample of 4000
      MSEs. A total of 170 out of 514 MSEs studied were included in the final analysis.
      Current status and characteristics of MSEs were identified and RI was assigned to
      chemicals in each industry. Based on the distribution of RIs, the high-risk MSEs
      were selected. These include: wood and products of wood, chemicals and chemical
      products, basic metals, other machinery and equipment, motor vehicles, trailer
      and semi-trailer manufacturing, and furniture manufacturing. Since these MSEs are
      high-risk ones, more attentions should be focused on them. This method can be
      applied to other workplaces with no previous history of quantitative workplace
      inspections.

PMID- 16610539
TI  - Development of interactive workplace improvement programs in collaboration with
      trade associations of small-scale industries.
AB  - Serial participatory action programs for reducing occupational safety and health
      risks were undertaken to know the types of support suited for small-scale
      industries. Working groups were formed with workplace people and occupational
      safety and health experts. It was agreed to develop an action-oriented strategy
      focusing on improving both work environment and productivity by making low-cost
      improvements through group work. Many workplace improvements achieved by
      participating enterprises and the group work procedures taken were analyzed. As
      supporting tools for effectively implementing the workplace improvement action
      programs, we developed action checklists according to industry and workplace
      implementation guides. Collections of local good examples also served as part of
      these support tools. These experiences show that keys to the sustainable action
      in small-scale industries are: (1) mobilization of the industry-wise network by
      trade associations, (2) an output-oriented strategy based on interactive group
      work and (3) the effective use of support tools such as low-cost action
      checklists and group work methods.

PMID- 16610540
TI  - Achievement of the POSITIVE (Participation-Oriented Safety Improvement by Trade
      Union InitiatiVE) activities in the Philippines.
AB  - The POSITIVE (Participation-oriented safety improvement by trade union
      initiative) programme was introduced into the Philippines in 1995. The monitoring
      of activities was carried out in 2004 among core trainers who had been trained
      before. The results of the questionnaire survey showed that the core trainers
      evaluated their activities satisfactory in general, and particularly the training
      activities were considered excellent. Also, the union workers who had been
      trained by the POSITIVE programme implemented improvements at the rate of around
      5 examples a year on average. It was of note that the installation ratio (the
      number of installations/that of plans) was higher in small- and medium-sized
      enterprises than in larger companies, although the numbers of plans and
      installations of improvements were greater in large enterprises. Together with
      the previous findings, the present results suggest that the POSITIVE-style
      participatory training program is effective and efficient for workers to take
      actions for the OSH in not only larger enterprises but also small enterprises.

PMID- 16610541
TI  - Neurobehavioral effects and hormones profile among spray painters.
AB  - A cross-sectional study was conducted in 25 spray painters and 35 control
      subjects to evaluate neurobehavioral function, and thyroid and reproductive
      hormones profile. This study indicated higher prevalence of psychological and
      neurological symptoms, and clinical findings among spray painters when compared
      with controls. Levels of TSH were significantly (p<0.01) elevated in spray
      painters over the control group (3.04 +/- 1.53 vs 1.88 +/- 1.07 microIU/ml, mean
      +/- SD), respectively. Two of the 25 spray painters acquired sub-clinical
      hypothyroidism, and one subject was detected with overt hypothyroidism. T4 levels
      were significantly (p<0.05) suppressed in spray painters while T3 was not changed
      significantly in both the groups. Reproductive hormones (LH, FSH, and
      testosterone) showed no significant changes in control and spray-painting group.
      However, two spray painters had abnormally high level of LH (26.43 and 12.22
      IU/l; normal range 0.5-10 IU/l). These subjects were also found to have
      abnormally higher level of FSH (38.63 and 14.11 IU/l; normal range 1.3-11.5
      IU/l). An isolated higher level of FSH (39.94 IU/l) was also observed in one
      spray painter. No abnormality in the level of LH was observed in control group
      while 3 subjects from this group had abnormally high level of FSH. Testosterone
      levels were under the normal range (3-12 ng/ ml) in both the groups. This study
      might suggest that spray painters are at risk of developing neurobehavioral,
      thyroid and reproductive problems.

PMID- 16610542
TI  - Chainat: a case study in occupational health and safety promotion for farmers.
AB  - The high rates of occupationally related injuries, accidents, and deaths in rural
      Thailand are of particular concern to public health officials, as well as the
      residents and workers living in these areas. In response to specific concerns
      raised by local residents and local health officials in Chainat Province,
      Thailand, the Work Improvement in Neighborhood Development (WIND) programme was
      introduced and implemented by means of the local Primary Care Unit (PCU). The
      objective was to improve farmers' knowledge of methods to improve occupational
      safety and to reduce the occurrence of occupationally related injuries,
      accidents, and deaths in the area. Local farmers, public health officers, and
      health volunteers from the PCU played a primary role in the programme, serving as
      trainers in the initial training of trainer session. Major activities included
      visiting a local farm to carry out a check-list improvement activity and active
      discussion among participants about potential improvements. Following the
      implementation of WIND in Chainat, a number of significant improvements in work
      conditions were noted, including construction of resting corners, plans to build
      toilets in the fields, improved knowledge about the dangers of chemical
      fertilizers and pesticides, and increased use of personal protective equipment.
      Furthermore, participants began making organic fertilizer and had independently
      developed an organic anti-snail pesticide. This integrative approach, achieved by
      including many different members of the community, in combination with government
      support and diligent follow-up, has proved to be particularly successful.

PMID- 16610543
TI  - Strengthening the self-care of women working in the informal sector: local fabric
      weaving in Khon Kaen, Thailand (Phase I).
AB  - The first phase of this study was undertaken using Participatory Action Research
      (PAR) to identify the factual situations of fabric-weaving women working in the
      informal sector in Thailand. The aims were to enhance the mutual understanding of
      the women and researchers concerning the problems faced by these women and to
      establish an action plan to address these problems. The participant group
      consisted of 107 women working in the informal sector from three local villages
      who voluntarily took part in the study. Data were collected using quantitative
      and qualitative methods through structured questionnaires, focus groups, in-depth
      interviews, participant observations, and field notes. The results of the study
      revealed that the women learned their health problems were related to work and
      their labor potentially placed them at a risk for illness. When the women
      realized the gravity of their situation, they attained a sense of empowerment and
      took the initiative in establishing action plans to address their problems.

PMID- 16610544
TI  - Promotion of a healthy work life at small enterprises in Thailand by
      participatory methods.
AB  - The major problems of small enterprises include unfavourable working conditions
      and environment that affect safety and health of workers. The WISE (Work
      Improvement in Small Enterprises) methodology developed by the ILO has been
      widely applied to improve occupational safety and health in small enterprises in
      Thailand. The participatory methods building on local good practices and focusing
      on practicable improvements have proven effective in controlling the occupational
      hazards in these enterprises at their sources. As a result of applying the
      methods in small-scale industries, the frequency of occupational accidents was
      reduced and the working environment actually improved in the cases studied. The
      results prove that the participatory approach taken by the WISE activities is a
      useful and effective tool to make owner/managers and workers in small enterprises
      voluntarily improve their own working conditions and environment. In promoting a
      healthy work life at small enterprises in Thailand, it is important to further
      develop and spread the approach.

PMID- 16610545
TI  - Evaluation of occupational environment in two textile plants in Northern India
      with specific reference to noise.
AB  - Occupational Noise exposure has been linked with a range of negative health
      effects by various researchers. The resulting injury of occupational hearing loss
      is also a well recognized and global problem. To protect workers from hearing
      damage due to noise exposure and other related health effects, a vast store of
      knowledge has been accumulated till date about its nature, etiology and time
      course. There is still ignorance, amongst majority of people working in
      industries in developing and third world countries including India about ill
      effects of exposure to high values of noise. The study being reported here has
      been carried out in two textile plants located in Northern Indian state of
      Punjab. Equivalent sound pressure level L(eq) has been measured in various
      sections of these plants with the help of a Class-I type digital sound level
      meter. The noise spectrum has been evaluated with the help of 1/3 octave filter
      set. A cross sectional study involving 112 workers exposed to different levels of
      occupational noise has been conducted. The results of the study establish the
      fact that noise level in certain sections of the plants i.e Loom Shed, Spinning,
      Ring Frame, TFO Area is more than the acceptable limit of 90 dBA for 8 h exposure
      stipulated by OSHA. The noise level in other sections like carding, blow room,
      combing etc., although is less than 90 dB(A), but is quite higher than limits
      used for assessment of noise for community response. Octave band analysis of the
      noise shows the presence of high sound level in 4,000 Hz frequency range, which
      can be a major reason for causing occupational hearing loss. The results of the
      interview questionnaire which included a number of parameters reveal the
      following; (i) only 29% workers are aware about the effects of noise on health
      (ii) 28% workers are using ear protectors (iii) the satisfaction with the working
      environment is related to noise level, as workers exposed to comparatively less
      noise level report better satisfaction (iv) 70% of the workers reported that high
      noise level causes speech interference (v) 42% workers report the noise to be
      annoying. The study thus demonstrates the presence of gross occupational noise
      exposure in both the plants and the author believes that occupational noise
      exposure and the related effects in India is a widespread problem.

PMID- 16610546
TI  - Evaluation of occupational health management in small-scale enterprises using a
      checklist for organic solvents.
AB  - The aim of this research was to clarify improvements in the occupational health
      management of small-scale enterprises by introducing the use of a checklist for
      organic solvents. We studied 25 small-scale enterprises producing lacquerware in
      Wakayama Prefecture, Japan. We specifically designed a manual for checking the
      occupational health management that included a checklist for self-evaluation. The
      survey using the manual led us to find that the median of workers was 4. All
      workshops were equipped with local exhaust ventilators for spraying work. Overall
      recognition of a need for the occupational safety and health by managers was not
      particularly high. The need was found for producing a documented work standard,
      properly dealing with or controlling organic solvents, thus preventing workers
      from exposure to organic solvents. Eighteen small-scale enterprises answered yes
      to more than 50 percent of items on the checklist. The results of the checklist
      exercise revealed some problems in spraying workshops, such as no documented work
      standard, no inspection of tools or local exhaust ventilators before work, no
      prevention against exposure to organic solvents, and insufficient measures taken
      for occupational health education. The results in this research pointed out some
      need to improvements in the occupational health management.

PMID- 16610547
TI  - Prevalence of and risk factors for low back pain among staffs in schools for
      physically and mentally handicapped children.
AB  - The objective of this study is to clarify the prevalence of and risk factors for
      low back pain (LBP) in schools for physically and mentally handicapped children.
      This study design is a cross-sectional study. The subjects included were 1,869
      staff members from 19 prefectural schools for children in Shizuoka Prefecture,
      Japan, which included schools for the blind, deaf-mutes, physically handicapped,
      and mentally retarded children. A total of 975 subjects completed two postal
      questionnaires which included morbidity, demographic factors, nursing activity,
      and psychosocial factors. The answer rate was 52%. The one-month prevalence of
      LBP was 45%. According to the classification of nursing activity, assistance in
      movement 1.67 (95% CI 1.27-2.14), excretory function 1.45 (1.11-1.88), and
      feeding 1.44 (1.10-1.90) showed significant increases in the odds ratio. The
      adjusted odds ratio significantly increased by 2.35 (1.78-3.11) in the group with
      depression symptoms as well as in the group with job stressors such as
      quantitative, qualitative, and physical work loads, job control, utilization of
      technique, interpersonal conflicts, and degree of satisfaction with their
      work/home life.

PMID- 16610548
TI  - Participatory ergonomic improvement in nursing home.
AB  - The number of nursing home has increased largely in Japan since 1990. The Long
      term Care Insurance in 2000 has accelerated the increase of nursing homes. The
      care giving and cooking in nursing homes have high risk factors of muscle
      skeletal diseases (MSDs). However, the working conditions have not yet been
      improved. Thus, the incidence of low back pain and cervico-brachial disorder is
      very high among the care workers and cooks. Therefore, it is important to prevent
      the MSDs among the care workers and cooks. This study has been conducted to make
      a model of the participatory improvement focusing on low back pain in a nursing
      home for three years. As a result of the study, many improvements have been
      implemented and the incidence of low back pain has been reduced.

PMID- 16610549
TI  - Occupational low back pain among workers in some small-sized factories in
      Ardabil, Iran.
AB  - The main purpose of this study was to assess some of the individual and
      occupational risk factors contributing to induction or intensification of LBP
      among the employees suffering from this problem in four small size factories in
      Ardabil, Iran. This study was a cross-sectional study that was conducted among
      the personnel of four industrial companies. Interview, questionnaire survey,
      medical examination (Lasegue test), radiographic evaluation, and ergonomic survey
      (using the NIOSH checklist) were the methods to collect data. The result of the
      study was divided into two parts: individual factors and work-related factors.
      The highest frequency of low back pain was observed in the age of 30-34 years
      old, medium height and heavy weight with 34.4, 84.4, and 33.0 percent,
      respectively. With regard to work-related factors, load lifting with 44.7 and
      body posture with 18.4 percent contributed to low back pain as the most important
      occupational causes among the patients. Observing recommended regulations and
      limitations of load lifting, modifying and optimizing ergonomic conditions in the
      workplace, selecting workers with suitable body strength on the basis of a pre
      employment examination and implementing a continuous educational program for
      employees were the most important methods recommended to prevent low back pain.

PMID- 16610550
TI  - The challenges of occupational health service centers in Japan.
AB  - The improvement of occupational health conditions in Small- and medium-scale
      enterprises (SMEs) is the most crucial issue in occupational health in Japan
      today. Improvement will depend on how occupational health services are provided
      to SMEs. Recently, Occupational Health Service Centers (OHSCs) providing
      occupational health services for SMEs have become more firmly established and
      expectations for further improvement in quality and quantity are high. In this
      way it is hoped that the challenges of providing "occupational health for all"
      can be met.

PMID- 16610551
TI  - A study of factors relating to work accidents among seamen.
AB  - In Japan, the accident rate for seamen is 5 times higher than that for all other
      industries. Many maritime work accidents are related to the poor ergonomic
      conditions of the working environment. It is particularly important to examine
      seamen safety in terms of vessel type and seamen age, as these factors are
      related to various sorts of accidents. In this paper, maritime work accidents
      were analyzed according to fundamental factors including vessel type, seamen age,
      and seamen rank. It is suggested that safety education should be provided
      according specifically to seamen age and vessel type, as they are revealed to be
      strong factors relating to maritime work accidents. Such education and further
      research may also lead to improvements in maritime equipment in relation to
      worker safety.

PMID- 16610552
TI  - Nationwide survey of occupational health activities in small-scale enterprises in
      Japan.
AB  - OBJECTIVES: In order to clarify the real condition of occupational health (OH)
      activities in small-scale enterprises (SSEs) at the nationwide level, we
      conducted a questionnaire study sent to SSEs. We selected SSEs according to their
      employee numbers published in the in "Census of Workplaces in 1999". SUBJECTS AND
      METHODS: About 2000 establishments were selected from the list in the "Census"
      describing the names and addresses of enterprises with 5 or more employees. The
      questionnaire included type of business, number of employees, independence, OH
      competent person, conduction of health examination, potential hazardous works and
      countermeasures (chemicals handling, computer work, etc), committee or other
      types of organizations for OH, and others. RESULTS: Two hundred eleven
      establishments with 1-4 employees, 779 establishments with 5-9 employees, 681
      establishments with 10-49 employees, 300 establishments with 50-99 employees, and
      57 establishments with more than 100 employees, a total of 2,029 establishments
      responded to the questionnaire. The types of businesses (the number of
      establishments) were construction (216 establishments), manufacturing (604),
      transportation and communication (216), wholesale and restaurants (390) and
      services (602). The rate of independent enterprises was 54.1% and branches 45.9%.
      Indicators of OH activities including selection of OH competent person,
      enforcement of OH guideline for computer work, OH education about the
      occupational health risks, enforcement of special health examinations and general
      health examinations in SSEs with 1-4 and 5-9 employees were worse than SSEs with
      10 or more employees. CONCLUSIONS: The differences of OH activities by scale of
      number of employees were clarified at a nationwide level. However, OH activities
      in SSEs with 1-4 employees were not clarified sufficiently. Various policies and
      methods should be established and implemented to improve the low level of OH
      activities in SSEs.

PMID- 16610553
TI  - The tendency of diseases among seamen during the last fifteen years in Japan.
AB  - Compared to workers on land, seamen working on the ocean are given only limited
      disease treatment. The aim of this paper is to clarify the actual condition of
      diseases among such seamen in an effort to improve measures that promote their
      health. We analyzed 51,641 cases of diseases that were reported to the Ministry
      of Land, Infrastructure and Transport from 1986 to 2000. The most prevalent
      diseases included disorders of the digestive system, followed by those of the
      musculoskeletal and the circulatory systems. The proportions of the three disease
      types were shown to vary by the type of work, ship, and occupation. One of the
      reasons for the variation in incidence between type of work and ship might result
      from differences in the voyage period in the given year. In explaining the varied
      incidences between occupations we hypothesize that differences in work systems
      and contents may be important variables to consider. It will be necessary to
      clarify the lifestyle and living environment of seamen to suggest appropriate
      measures for combating diseases prevalent in this population.

PMID- 16610554
TI  - Characteristics of lifestyle and health status of workers in small-scale
      enterprises in Japan.
AB  - This study was conducted to clarify the characteristics of small-scale
      enterprises (SSEs) with fewer than 50 workers, which employ 62.2% of all Japanese
      workers. Subjects were 71,183 workers employed at 1,761 workplaces in Tochigi,
      Japan, in 2002. Frequencies of abnormal lifestyle and health check-up data were
      described according to the category of the enterprise. Adjusted odds ratios (ORs)
      of the abnormal findings were calculated by logistic regression analysis. Dose
      response relationships were calculated by trend tests. The frequency of abnormal
      findings was higher in SSEs than in other categories of enterprises. The ORs of
      work intensity, alcohol consumption, current smoker, and the Brinkmann index were
      higher in SSEs than in large-scale enterprises (LSEs) and were also significant
      in trend tests. The ORs of audiometry, hypertension, glucose in urine and ECG in
      males and females, BMI, liver function, lipid metabolism, and blood sugar in
      females, chest X-ray, and anemia in males were higher in SSEs. Audiometry,
      hypertension, anemia, ECG in both males and females; chest X-ray, and glucose in
      urine in males, and liver function, lipid metabolism and blood sugar in females
      showed significant results in trend tests. Overall health and healthy lifestyle
      in SSEs were worse than in LSEs.

PMID- 16610555
TI  - Injury rate as an indicator of business success.
AB  - Health and safety professionals and organizations have often suggested that
      promoting and improving health and safety in the workplace will improve business
      success. We conducted a study of all new small businesses that registered with
      the Workers' Compensation Board of British Columbia (WCB of BC) in the years
      1993, 1995, 1996 and 1997, assessing their injury rate in the first 5 complete
      years of business. The data set represents 53,913 new businesses and 19,332
      claims. Businesses were grouped by the number of years between registering for
      WCB coverage and termination of coverage. Injury rates were determined for each
      calendar year for each industry sector as injuries per 100 person-years, based on
      payroll information provided by the businesses. Across all industries, businesses
      that failed between 1 and 2 yr of start-up had an average injury rate of 9.71
      while businesses that survived more than 5 yr had an average injury rate of only
      3.89 in their first year of business (p<0.000001). The WCB of BC demonstrated a
      statistical correlation between health and safety in the workplace and the
      survival of a small business.

PMID- 16610556
TI  - Research priorities in occupational safety and health: a review.
AB  - Changes in the world of work in the last few decades have markedly affected
      questions regarding occupational safety and health (OSH). Jobs in our economy
      continue to shift from manufacturing to services. Longer hours, shift work,
      reduced job security, temporary work are realities in the modern workplace, new
      chemicals, materials, processes are developed at an ever accelerating pace. The
      workforce is also changing. It will become older and more racially diverse and
      women are increasing. These changes present new challenges to protect worker
      safety and health and it was been indispensable to redefine priorities, by
      consulting all those involved in OSH. The present study therefore made a critical
      comparative analysis of the main published projects to identify research
      priorities in the OSH field, comparing methods, approaches and results.
      Comparison of the priority areas established in each of these studies is
      inherently difficult due to differences in socio-cultural backgrounds, in the
      methods employed to identify priority topics, and the many factors involved.
      However, it is clear that the Delphi technique is widely used as a reliable
      method, in that it covers a broad range of qualified witnesses, from a variety of
      backgrounds--such as trade union representatives and researchers--providing
      different viewpoints. It also takes account of the intrinsic features of OSH
      which--compared to other disciplines--involves multidisciplinary factors calling
      into play a range of scientific settings, such as toxicologists, molecular
      biologists, epidemiologists, occupational hygienists and occupational physicians.
      This analysis showed how important it is to reach consensus among all those
      operating in the OSH sector, in order to establish standard methods that can be
      applied in different contexts, and give results that can be validly compared.

PMID- 16610557
TI  - Urinary 8-hydoxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels
      in Aldh2 knock-out mice under acetaldehyde exposure.
AB  - To clarify the carcinogenicity of acetaldehyde when associated with ALDH
      (aldehyde dehydrogenase) 2 polymorphism, Aldh2 knock-out (Aldh2-/-) mice and
      their wild type (Aldh2+/+) mice were exposed to two different concentrations of
      acetaldehyde (125 ppm and 500 ppm) for two weeks. Aldh2-/- mice, which have the
      same genetic background as C57BL/6J (wild mice) except for the Aldh2 gene, were
      used as models of humans who lack ALDH2 activity. Urinary 8-hydroxydeoxyguanosine
      (8-OHdG) and plasma malondialdehyde (MDA) levels were measured as indicators of
      oxidative DNA damage and lipid peroxidation, respectively. At 125 ppm
      acetaldehyde exposure for 12 d, urinary 8-OHdG levels in Aldh2+/+ mice did not
      increase. However, urinary 8-OHdG levels in Aldh2-/- mice were slightly increased
      by the end of the exposure. On the other hand, plasma MDA levels did not increase
      in either Aldh2-/- orAldh2+/+ mice. At 500 ppm, urinary 8-OHdG levels in both
      Aldh2-/- and Aldh2+/+ mice significantly increased after 6 and 12 d, but there
      was no genetic difference. On the other hand, plasma MDA levels in Aldh2+/+ and
      Aldh2-/- mice did not increase at either 125 ppm or 500 ppm after two weeks of
      exposure. In conclusion, it is suspected that DNA was damaged by acetaldehyde
      inhalation, and that susceptibility to acetaldehyde varies according to Aldh2
      genotype.

PMID- 16610558
TI  - Physical activity and selected cardiovascular risk factors in middle-aged male
      personnel of self-defense forces.
AB  - We cross-sectionally analyzed the association between duration of physical
      activity and the presence of selected cardiovascular risk factors in the middle
      aged male personnel of the Self-Defense Forces who underwent retirement check-up
      (n = 974). In a univariate regression analysis, duration of high intensity
      physical activity but not that of moderate or low intensity physical activity
      inversely correlated with body mass index (BMI), triglyceride, fasting plasma
      glucose, white blood cell (WBC) count and systolic blood pressure. No intensity
      categories of physical activity correlated with total cholesterol. In a
      multivariate logistic regression analysis adjusted for lifestyle factors and the
      rank, the odds ratio per 1 h/wk increase in high intensity physical activity was
      .88 (95% confidence interval (CI) .80-.97; P=.007) for the presence of obesity
      (BMI 25.0 kg/m2), .88 (95% CI .81-.95; P = .002) for hypertrigly ceridemia, .87
      (95% CI .76-.99; P=.034) for type 2 diabetes, and .90 (95% CI .82-.99; P=.037)
      for hypertension. Neither hypercholesterolemia nor high WBC count (> or =
      6,900/microl) was associated with high intensity physical activity. High
      intensity physical activity inversely correlated with traditional cardiovascular
      risk factors in the middle-aged men.

PMID- 16610559
TI  - Respirable dust exposure and respiratory health in male Taiwanese steelworkers.
AB  - The objective of this cross-sectional study was to investigate the prevalence and
      determinants of respiratory symptoms and lung function and their association with
      occupational dust exposure in Taiwanese steelworkers. The study was conducted on
      an integrated-steel company in Taiwan from March 1989 to February 1990. After
      excluding workers in the coke ovens and ex-smokers, we performed physical
      examinations on 1,339 male workers in the iron making and steel making factories.
      Subjects were interviewed regarding respiratory symptoms using a Chinese version
      of the American Thoracic Society respiratory questionnaire and were examined with
      respect to their lung function using spirometry. Objective dust exposure was
      measured using personal air sampling with 277 valid samples. Prevalences of cough
      frequently, chronic cough, phlegm frequently, chronic phlegm, wheezing
      occasionally, and breathlessness were 11.4%, 9.3%, 14.6%, 11.9%, 2.6%, and 6.5%,
      respectively. Duration of employment, smoking, subjective dustiness, and past
      respiratory illnesses can predict these respiratory symptoms. Average respirable
      dust exposure significantly decreased the forced vital capacity (FVC) and forced
      expiratory volume in one second (FEVI.0) in smoking workers. In the non-smokers,
      an effect of respirable dust exposure on FEVl.0/FVC was shown. Since the main
      ingredients of dust in such a steelworks usually contained mixtures of oxides and
      silicates other than silica dust, respirable dust exposure in steelworks might
      impair lung function, especially among smokers.

PMID- 16610560
TI  - Maximum acceptable weight of manual load carriage for young Taiwanese males.
AB  - This study examined the maximum acceptable weight of carriage (MAWC) for young
      Taiwanese males experienced in manual load carriage tasks. The elements of the
      examined load carriage tasks included lifting a box from the floor to the waist
      height, turning around while holding the box, carrying the box at the waist
      height for a distance, lowering the box to the floor, turning around, and walking
      unloaded back to the original position. Subjects performed the load carriage
      tasks over different levels of carriage distance, frequency, box width (sagittal
      dimension), and handle according to a response surface design. The results showed
      that subjects' MAWC decreased with carriage distance, frequency and box width,
      while heart rate and rate of perceived exertion (RPE) increased with carriage
      distance, frequency and box width. The MAWC for box with handles was on average
      1.5 kg more than that for box without handles, while the effects of handle on
      heart rate and RPE were very trivial.

PMID- 16610561
TI  - Green chemistry in urinalysis for trichloroethanol and trichloroacetic acid as
      markers of exposure to chlorinated hydrocarbon solvents.
AB  - The aim of the present study was to develop a method of urinalysis for
      trichloroacetic acid (TCA) and trichloroethanol (TCE), and therefore total
      trichloro-compounds (TTC) as the sum, with least use of hazardous chemicals,
      being green in that sense. After acid hydrolysis followed by dilution with an
      ethanol (EtOH)-methanol (MeOH)-water mixture, capillary gas-choromatography with
      an electron-capture detector can quantify TCA and TCE in the diluted hydrolyzate.
      Comparison studies showed that the results were identical among three methods,
      i.e., 1. the method developed in the present study, 2. a head-space GC with acid
      hydrolysis of conjugated TCE and methyl-esterification of TCA, and 3. traditional
      colorimetry with Fujiwara reaction. When applied to exposure-excretion analysis,
      the three methods gave results reproducible to each other. Over-all evaluation
      therefore was such that the method developed in the present study is as equally
      reliable as previously developed methods. It should be further noted that the
      procedures are very simple, with minimum use of occupationally or environmentally
      hazardous chemicals. In case the determination of only TCA is requested, it is
      possible to skip the hydrolysis step so that the treatment prior to the GC
      analysis is even simpler, i.e., just a 60-fold dilution of the urine sample with
      the EtOH-MeOH-water mixture. It was also demonstrated that correction of urinary
      analyte levels for urine density in terms of creatinine or specific gravity did
      not improve the correlation with the intensity of TRI exposure.

PMID- 16610562
TI  - Peritoneal tuberculosis (? carcinomatosis).

PMID- 16610563
TI  - The case for expanding human immunodeficiency virus testing.

PMID- 16610564
TI  - Evaluation of the Centers for Disease Control and Prevention's recommendations
      regarding routine testing for human immunodeficiency virus by an inpatient
      service: who are we missing?
AB  - OBJECTIVE: To assess the proportion of hospitalized patients who tested positive
      for human immunodeficiency virus (HIV) by a routine inpatient testing service, as
      recommended by the Centers for Disease Control and Prevention, who might not have
      been identified had routine testing not been offered. PATIENTS AND METHODS: In
      this retrospective cohort study, the medical records of patients who tested HIV
      positive by the inpatient testing service between 1999 and 2003 were compared
      with the medical records of inpatients who tested HIV negative by the inpatient
      testing service and the medical records of patients who tested HIV positive in
      ambulatory settings. We compared HIV risk factors, discharge diagnoses, CD4 cell
      counts, and HIV RNA concentrations. RESULTS: A total of 243 patients participated
      in this study: 81 patients who tested HIV positive and 81 who tested HIV negative
      by the inpatient testing service, and 81 patients who tested HIV positive in
      ambulatory settings. Both HIV-positive inpatients and HIV-positive outpatients
      had similar frequencies of HIV risk factors (46% vs 43%; P=.75). Both groups
      differed significantly from HIV-negative inpatients (4%; P<.001). Comparing HIV
      positive inpatients with HIV-positive outpatients, CD4 cell counts were lower
      (196 vs 371 cells/mm3; P<.001), and HIV RNA levels were higher (4.61 vs 4.09 Iog,
      HIV RNA; P=.001). At diagnosis, 64 HIV-positive inpatients (79%) met criteria for
      acquired immunodeficiency syndrome compared with 21 HIV-positive outpatients
      (26%) (P<.001). CONCLUSION: Patients who tested HIV positive through inpatient
      testing have more advanced disease than those identified as outpatients. Half of
      these patients would not have been identified had testing not been routinely
      offered. Routine inpatient HIV testing offers an important opportunity to
      identify patients with HIV infection.

PMID- 16610565
TI  - Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal
      morphological features predict the presence of myofilament mutations.
AB  - OBJECTIVE: To examine the relationship among age, septal morphological subtype,
      and presence of hypertrophic cardiomyopathy (HCM)-associated myofilament
      mutations. PATIENTS AND METHODS: Comprehensive mutation analysis of the 8 HCM
      susceptibility genes that encode the myofilaments of the cardiac sarcomere was
      performed previously in 382 unrelated patients with HCM. Blinded to genotype
      status, we used echocardiography to characterize the left ventricular
      morphological features. Multivariate regression was used to assess the
      relationship among morphological subtypes, clinical data, and genetic variables.
      RESULTS: The mean +/- SD age of the patients was 41.6+/-19.0 years, with 126
      patients 50 years or older at initial diagnosis. The septal morphological subtype
      was sigmold in 181 (47%), reverse in 132 (35%), apical variant in 37 (10%), and
      neutral in 32 (8%). The HCM-associated myofilament mutations were Identified in
      143 patients (37%). Multivariate analysis showed that the reverse curvature
      septal morphological subtype was a strong predictor of genotype-positive status
      (odds ratio, 21; P<.001). Overall, the yield of HCM genetic testing was 79% in
      the setting of reverse curvature HCM but only 8% in sigmold septal HCM.
      CONCLUSION: In stark contrast to HCM in young patients, elderly patients with HCM
      display a predominantly sigmoid septal morphological subtype and uncommonly have
      perturbations of known HCM susceptibility genes. Independent of age, septal
      morphological subtype strongly predicts the presence or absence of HCM-associated
      myofilament mutations and may enable echocardiography-guided genetic testing for
      HCM.

PMID- 16610566
TI  - The evolution of ureteroscopy: a modern single-institution series.
AB  - OBJECTIVES: To evaluate a modern ureteroscopy series, including the use of new
      technological advances, operative procedures, and potential complications, at a
      single institution and to compare our current experience with our prior published
      series and the current literature. MATERIAL AND METHODS: We retrospectively
      reviewed 1000 consecutive ureteroscopies performed in 961 patients from December
      1999 to February 2003 at our institution. RESULTS: Semirigid and flexible
      ureteroscopes were used in 60.3% and 37.0% of the cases, respectively. In 2.6% of
      cases, a combination of both rigid and flexible ureteroscopes was required. The
      most common indications for ureteroscopy were as follows: stone, 57.9%;
      diagnostic, 20.6%; and urothelial carcinoma, 12.6%. Of the stones treated, 31.8%
      were proximal or middle and 59.1% distal. The overall, proximal, and distal stone
      free rates were 91.7%, 87.3%, and 94.2%, respectively. Average operative time was
      81 minutes (range, 5-280 minutes). Average follow-up was 2.36 months (range, 1-24
      months). The overall complication rate was 1.9% (18/961), including a 0.2%
      (2/961) incidence of ureteral strictures. CONCLUSION: Current practice trends
      have shifted to an increased use of flexible ureteroscopes and more frequent
      ureteroscopic treatment of proximal calculi. Our single treatment stone-free
      rates are competitive with quoted shock wave lithotripsy success. In addition,
      there has been a decrease in ureteroscopic-associated complications in our
      series, with no ureteral avulsions. The improvements in treatment success and
      decrease in complications may be secondary to advances in ureteroscopic
      technology.

PMID- 16610567
TI  - Spanish cross-cultural adaptation and validation of the National Institutes of
      Health Stroke Scale.
AB  - OBJECTIVES: To adapt and validate a Spanish-language version (SV) of the National
      Institutes of Health Stroke Scale (NIHSS) to facilitate its use in Spanish
      speaking contexts. PATIENTS AND METHODS: The methods recommended by the
      International Quality of Life Assessment Project were followed. Two forward
      translations and 1 back translation of the NIHSS were developed to ensure lingual
      and cultural equivalence. A final revised SV-NIHSS was administered by 8
      physicians to patients with stroke in 3 clinics in Buenos Aires, Argentina, from
      September 2003 to December 2003. RESULTS: The study included 102 patients (mean
      +/- SD age, 73.3+/-6.5 years; 56% women) with stroke (86% ischemic). The SV-NIHSS
      mean baseline score was 9.78+/-7.04. Interrater reliability was Independently
      evaluated for 98 patients, showing a high agreement: kappa, 0.77 to 0.99 for the
      15 items; interrater correlation coefficient, 0.991 (95% confidence Interval,
      0.987-0.994). Intrarater reliability was excellent: kappa, 0.86 to 1.00 for the
      15 items; mean intrarater correlation coefficient, 0.994 (95% confidence
      interval, 0.991-0.996). Construct validity was also adequate; the SV-NIHSS had a
      negative correlation with baseline Glasgow Coma Scale (Spearman coefficient = 
      0.574, P < .001) and with Barthel index at 3 months (Spearman coefficient = 
      0.658, P < .001). Patients with different Rankin scores at 3 months also had
      significantly different baseline SV-NIHSS scores, from a mean of 4.29+/-2.21 for
      Rankin score of 0 to a mean of 29.40+/-3.97 for Rankin score of 6 (P < .001).
      CONCLUSION: This study shows that a Spanish-language version of the NIHSS
      developed with internationally recommended methods is reliable and valid when
      applied in a Spanish-speaking setting.

PMID- 16610568
TI  - Cogan syndrome: a retrospective review of 60 patients throughout a half century.
AB  - OBJECTIVE: To evaluate the disease manifestations and clinical course of patients
      affected by Cogan syndrome (a syndrome of nonsyphilitic interstitial keratitis
      and vestibuloauditory symptoms) at a single institution during roughly a half
      century. PATIENTS AND METHODS: Medical records of all patients diagnosed as
      having Cogan syndrome at the Mayo Clinic in Rochester, Minn, and who were
      followed up from 1940 to 2002 were comprehensively reviewed. Otolaryngologic,
      ophthalmologic, and systemic manifestations of disease were analyzed. Analysis
      included patient demographics, presenting manifestations, delayed manifestations,
      laboratory testing, physical examination features, therapeutic interventions,
      disease course, and hearing and vision outcomes. RESULTS: Sixty patients were
      identified as having Cogan syndrome, with follow-up from 1940 to 2002. Most
      patients presented initially with vestibuloauditory symptoms, most commonly
      sudden hearing loss (50%). The most common inflammatory ophthalmologic condition
      noted was bilateral interstitial keratitis. Headache (40%), fever (27%), and
      arthralgia (35%) were the most frequently encountered systemic manifestations.
      Evidence of aortitis was found in 12% of patients. Complete hearing loss was
      eventually noted in 52% of affected patients, whereas permanent loss of any
      degree of vision was uncommon. Cochlear implantation outcomes were uniformly
      good. Death directly or indirectly attributed to the effects of Cogan syndrome
      was noted in 4 patients. CONCLUSIONS: The major disease-related morbidities were
      due to vestibuloauditory disease and only infrequently due to systemic
      manifestations such as vasculitis, with or without aortitis. Cochlear
      implantation has been of major benefit in modern hearing rehabilitation for this
      patient population. We advise caution before institution of protracted courses of
      high-dose corticosteroids and/or chemotherapy for patients without pronounced
      systemic disease or severe eye disease unmanageable by topical or periocular
      corticosteroids alone.

PMID- 16610569
TI  - Healing America's ailing health care system.

PMID- 16610570
TI  - Cutaneous malignant melanoma.
AB  - Skin cancer has become the most common neoplasm in the United States. With early
      diagnosis and appropriate management, most skin cancers have an overall 5-year
      survival rate of 95%. Cutaneous malignant melanoma (CMM), however, has a
      significantly higher morbidity and mortality, resulting in 65% of all skin cancer
      deaths. Although the long-term survival rate for patients with metastatic
      melanoma is only 5%, early detection of CMM carries an excellent prognosis, with
      surgical excision often being curative. Primary care physicians can play a
      critical role in reducing morbidity and mortality from CMM by recognizing
      patients at risk, encouraging the adoption of risk-reducing behaviors, and
      becoming adept at identifying suspicious lesions.

PMID- 16610571
TI  - Metastatic malignant melanoma of the gastrointestinal tract.
AB  - Malignant melanoma is one of the most common malignancies to metastasize to the
      gastrointestinal (GI) tract. Metastases to the GI tract can present at the time
      of primary diagnosis or decades later as the first sign of recurrence. Symptoms
      may include abdominal pain, dysphagia, small bowel obstruction, hematemesis, and
      melena. We report 2 cases of malignant melanoma metastatic to the GI tract,
      followed by a review of the literature. The first case is a 72-year-old man who
      underwent resection of superficial spreading melanoma on his back 13 years
      previously who presented with dysphagia. A biopsy specimen of a mucosal fold in a
      gastric fundus noted during endoscopy was taken and revealed metastatic malignant
      melanoma, which was resected 1 month later. Three weeks later, the patient was
      found to have an ulcerated jejunal metastatic melanoma mass, which was also
      resected. The second case is a 63-year-old man with an ocular melanoma involving
      the chorold of the left eye that had been diagnosed 4 years previously, which had
      been excised several times, who presented with anorexia, dizziness, and fatigue.
      He was found to have cerebellar and stomach metastases. He underwent adjuvant
      radiation therapy, chemotherapy, and surgical resection of the gastric melanoma
      metastasis. In patients with a history of melanoma, a high index of suspicion for
      metastasis must be maintained if they present with seemingly unrelated symptoms.
      Diagnosis requires careful inspection of the mucosa for metastatic lesions and
      biopsy with special immunohistochemical stains. Management may include surgical
      resection, chemotherapy, immunotherapy, observation, or enrollment in clinical
      trials. Prognosis is poor, with a median survival of 4 to 6 months.

PMID- 16610572
TI  - Aspirin and clopidogrel resistance.
AB  - Despite aspirin's and clopidogrel's proven benefit in reducing cardiovascular
      (CV) events, recurrent CV events still occur in patients receiving antiplatelet
      therapy. Many of these patients are resistant or only partially responsive to the
      antiplatelet effects of aspirin and clopidogrel, as determined by standard
      platelet assays. However, current clinical guidelines do not support routine
      screening for aspirin or clopidogrel resistance, in part because determination of
      the most appropriate screening test has not been established. This review
      attempts to (1) describe the phenomena of clinical aspirin and clopidogrel
      resistance (ie, treatment failure), (2) discuss the complexity of defining and
      identifying aspirin and clopidogrel resistance, (3) identify factors that may be
      responsible for aspirin and clopidogrel resistance, (4) outline several standard
      platelet function assays and their limitations, and (5) describe potential new
      antiplatelet therapies that may benefit aspirin- or clopidogrel-resistant
      patients.

PMID- 16610573
TI  - Vancomycin-resistant enterococci: colonization, infection, detection, and
      treatment.
AB  - Vancomycin-resistant enterococci (VRE) are becoming a major concern in medical
      practice. Their increased prevalence and their ability to transfer vancomycin
      resistance to other bacteria (including methicillin-resistant Staphylococcus
      aureus) have made them a subject of close scrutiny and intense investigation.
      Colonization is usually acquired by susceptible hosts in an environment with a
      high rate of patient colonization with VRE (eg, intensive care units, oncology
      units). Vancomycin-resistant enterococci can survive in the environment for
      prolonged periods (>1 week), can contaminate almost any surface, and can be
      passed from one patient to another by health care workers. Whether VRE
      colonization leads to infection depends on the health status of the patient.
      Whereas immunocompetent patients colonized with VRE are at low risk for
      infection, weakened hosts (patients with hematologic disorders, transplant
      recipients, or severely ill patients) have an increased likelihood of developing
      infection following colonization. Quinupristin-dalfopristin and linezolid are
      among the anti-infective agents that have recently become available to treat
      infection caused by VRE. Other antimicrobials are currently under development.
      Molecular techniques such as polymerase chain reaction and standard culture
      studies are being used to detect VRE colonization, infection, and outbreaks.

PMID- 16610574
TI  - 63-year-old woman with acute chest pain.

PMID- 16610575
TI  - Severe hepatotoxicity associated with use of a dietary supplement containing
      usnic acid.
AB  - Dietary supplements containing usnic acid are marketed for weight loss and have
      been associated with hepatotoxicity. The specific ingredient responsible for the
      hepatotoxicity is currently unknown. We describe 2 patients who developed severe
      hepatotoxicity within 3 months of taking a dietary supplement containing usnic
      acid. One patient developed fulminant hepatic failure requiring emergency liver
      transplantation; the other developed submassive hepatic necrosis but did not
      require transplantation. Thorough investigation, including histopathological
      examination of the liver, revealed no other cause of acute liver injury. Usnic
      acid hepatotoxicity should be considered as a possible etiologic factor in
      patients presenting with fulminant hepatic failure, especially if they have been
      taking dietary supplements for weight reduction.

PMID- 16610576
TI  - Variant angina associated with bitter orange in a dietary supplement.
AB  - The Food and Drug Administration has banned the sale of ephedrine-based weight
      loss products because of their association with many cardiovascular adverse
      effects. Bitter orange is now being used as a stimulant in "ephedra-free" weight
      loss supplements but was recently implicated in adverse cardiovascular sequelae.
      To our knowledge, this report describes the first case of variant angina
      associated with bitter orange in a dietary supplement.

PMID- 16610577
TI  - Rhabdomyolysis after ingestion of "foxy," a hallucinogenic tryptamine derivative.
AB  - "Foxy methoxy" (chemical name, 5-methoxy-N,N-diisopropyltryptamine) is a
      hallucinogenic tryptamine that has been abused with increasing frequency since
      its appearance in the late 1990s. Like other drugs in this class, foxy frequently
      produces feelings of euphoria, disinhibition, and auditory as well as visual
      hallucinations. The drug has been linked to adverse effects, including
      restlessness, agitation, gastrointestinal distress, and muscle tension. In light
      of the relatively recent advent of foxy as a drug of abuse and given the
      inability of commercial toxicologic screening tests to detect the presence of
      hallucinogenic tryptamines, additional adverse effects seem probable. We report
      ingestion of foxy by a healthy 23-year-old man that resulted in rhabdomyolysis
      and transient acute renal failure.

PMID- 16610578
TI  - Atypical myeloproliferative disorders: diagnosis and management.
AB  - Myeloid disorders constitute a subgroup of hematological malignancies that is
      separate from lymphoid disorders. The World Health Organization system for
      classification of tumors of the hematopoietic system divides myeloid disorders
      into acute myeloid leukemia and chronic myeloid disorders based on the presence
      or absence, respectively, of acute myeloid leukemia--defining morphological and
      cytogenetic features including the presence of 20% or more myeloblasts in either
      the bone marrow or the peripheral blood. A recently proposed semimolecular
      classification system for chronic myeloid disorders recognizes 3 broad
      categories: the myelodysplastic syndrome, classic myeloproliferative disorders
      (MPD), and atypical MPD. Classic MPD includes polycythemia vera, essential
      thrombocythemia, myelofibrosis with myeloid metaplasia, and chronic myeloid
      leukemia. Both myelodysplastic syndrome and BCR/ABL-negative classic MPD were
      previously discussed as part of the current ongoing symposium on hematological
      malignancies. The current review focuses on the diagnosis and treatment of both
      molecularly defined and clinicopathologically assigned categories of atypical
      MPD: chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, chronic
      neutrophilic leukemia, chronic basophilic leukemia, chronic eosinophilic
      leukemia, idiopathic eosinophilia including hypereosinophilic syndrome, systemic
      mastocytosis, unclassified MPD, and eosinophilic/mast cell disorders associated
      with mutations of platelet-derived growth factor receptors alpha (PDGFRA) and
      beta (PDGFRB), FGFR1, and KIT.

PMID- 16610579
TI  - Tramadol challenge for relief of intractable central poststroke pain.

PMID- 16610580
TI  - Clinical remission of acquired thrombasthenia with low-dose methotrexate in a
      patient with systemic lupus erythematosus.

PMID- 16610581
TI  - Recurrent infections in multiple myeloma.

PMID- 16610582
TI  - Hair analysis for detection of psychotropic drug use.

PMID- 16610583
TI  - Standardized white spot syndrome virus (WSSV) inoculation procedures for
      intramuscular or oral routes.
AB  - In the past, strategies to control white spot syndrome virus (WSSV) were mostly
      tested by infectivity trials in vivo using immersion or per os inoculation of
      undefined WSSV infectious doses, which complicated comparisons between
      experiments. In this study, the reproducibility of 3 defined doses (10, 30 and 90
      shrimp infectious doses 50% endpoint [SID50]) of WSSV was determined in 3
      experiments using intramuscular (i.m.) or oral inoculation in specific pathogen
      free (SPF) Litopenaeus vannamei. Reproducibility was determined by the time of
      onset of disease, cumulative mortality, and median lethal time (LT50). By i.m.
      route, the 3 doses induced disease between 24 and 36 h post inoculation (hpi).
      Cumulative mortality was 100% at 84 hpi with doses of 30 and 90 SID50 and 108 hpi
      with a dose of 10 SID50. The LT50 of the doses 10, 30 and 90 SID50 were 52, 51
      and 49 hpi and were not significantly different (p > 0.05). Shrimp orally
      inoculated with 10, 30 or 90 SID50 developed disease between 24 and 36 hpi.
      Cumulative mortality was 100% at 108 hpi with doses of 30 and 90 SID50 and 120
      hpi with a dose of 10 SID50. The LT50 of 10, 30 and 90 SID50 were 65, 57 and 50
      hpi; these were significantly different from each other (p < 0.05). A dose of 30
      SID50 was selected as the standard for further WSSV challenges by i.m. or oral
      routes. These standardized inoculation procedures may be applied to other
      crustacea and WSSV strains in order to achieve comparable results among
      experiments.

PMID- 16610584
TI  - Immune response and disease resistance of Oreochromis mossambicus to Aeromonas
      hydrophila after exposure to hexavalent chromium.
AB  - The objective of this study was to investigate the effect of chronic exposure to
      sublethal concentrations of hexavalent chromium (K2Cr2O7) on the immune response
      and disease resistance of Oreochromis mossambicus (Peters) to bacterial Aeromonas
      hydrophila infection. Fish (45 to 50 g) were exposed to 0.005, 0.05, 0.5, and 5
      mg l(-1) [0.01, 0.1, 1, and 10% LC50, respectively] of hexavalent chromium Cr
      (VI) for 28 d. The specific immune response was assessed by antibody response to
      A. hydrophila by bacterial agglutination assay, and to sheep red blood cells
      (SRBC) by plaque forming cell (PFC) assay. In addition, nonspecific immune
      mechanisms were assessed by serum lysozyme activity and reactive nitrogen
      intermediates, the latter in terms of nitric oxide (NO) production by peripheral
      blood leucocytes. Overall immunity was assessed by disease resistance against
      live virulent A. hydrophila. The study clearly indicated that chronic exposure of
      fish to 0.5 and 5 mg l(-1) of chromium (VI) decreased both nonspecific and
      specific parameters of the immune system, which resulted in a lower disease
      resistance to A. hydrophila. Interestingly, 0.05 mg l(-1) of Cr (VI) enhanced
      disease resistance and both nonspecific and specific immune responses to A.
      hydrophila. Our study revealed a concentration-dependent modulation of the immune
      system by chromium (VI), as demonstrated by suppressive or stimulatory effects on
      lymphocytes, lysozyme, phagocytic killing mechanisms, and disease resistance in
      O. mossambicus.

PMID- 16610585
TI  - Immunofluorescent test for simultaneous detection of Edwardsiella ictaluri and
      Flavobacterium columnare.
AB  - Enteric septicemia of catfish (ESC) and columnaris disease are 2 bacterial
      diseases significantly affecting the aquaculture industry, and thus rapid
      diagnosis of disease is imperative for making judicious management decisions. A
      rapid indirect fluorescent antibody (IFA) test with antibody conjugated
      fluorochromes having 2 different spectral properties (Alexa Fluor 488-emitting
      green fluorescence, and Alexa Fluor 594-emitting red fluorescence) was compared
      with bacteriological culture (accepted standard) for simultaneous detection of
      Edwardsiella ictaluri (EI) and Flavobacterium columnare (FC) in 3 groups of
      experimentally infected channel catfish (Ictalurus punctatus Rafinesque), and a
      fourth group that acquired an aquarium-infection with F. columnare. A total of
      303 samples (derived from kidney, brain and nares) from 101 fish were
      concurrently examined by both tests. Fish in the 3 experimentally infected groups
      (I to III) were culture positive for the bacteria with which they were infected,
      and fish in Group IV, (the spontaneously infected fish) revealed F. columnare
      only. The IFA test compared favorably in sensitivity (EI= 80.7 %; FC = 87.2%) and
      specificity (EI = 83.9%; FC = 88.9%) with the standard bacteriological culture.
      The positive predictive value (EI = 96.2% Group I, 90.8% Group II, 93.7% Groups I
      and II combined; FC = 95.2% Group II, 95.3% Groups II, III and IV combined) was
      high, while the negative predictive value (EI = 66.7% Group I, 31.3% Group II,
      59.5% Groups I and II combined; FC = 73.7% Group II, 72.7% Groups II, III and IV
      combined) was relatively low. The IFA test will serve as an efficient tool for
      rapid simultaneous detection of E. ictaluri and F. columnare in outbreaks of
      disease.

PMID- 16610586
TI  - Myxozoan pathogens in cultured Malaysian fishes. I. Myxozoan infections of the
      sutchi catfish Pangasius hypophthalmus in freshwater cage cultures.
AB  - Cage-cultured sutchi catfish Pangasius hypophthalmus (Sauvage, 1878), a favourite
      food fish in Southeast Asia, proved to be infected by 6 myxozoan species. Three
      species belonged to the genus Hennegoides (H. berlandi, H. malayensis, and H.
      pangasii), 1 to Henneguya (H. shariffi) and 2 to Myxobolus (M. baskai, and M.
      pangasii). Five myxozoans infected the gills and 1 was found on the spleen.
      Myxozoans infecting the gills were characterised by a specific site selection. H.
      shariffi sp. n. and H. berlandi sp. n. formed plasmodia in the multi-layered
      epithelium of the gill filaments. Of the 2 vascular species H. pangasii sp. n.
      developed in the gill arteries, while M. baskai sp. n. infected the capillary
      network of the gill lamellae. Plasmodia of H. malayensis sp. n. were found inside
      the cartilaginous gill rays of the filaments. Large plasmodia of M. pangasii sp.
      n. were located in a groove of the spleen but they affected only the serosa layer
      covering the spleen.

PMID- 16610587
TI  - Myxozoan pathogens in cultured Malaysian fishes. II. Myxozoan infections of
      redtail catfish Hemibagrus nemurus in freshwater cage cultures.
AB  - Cage-cultured Asian redtail catfish Hemibagrus nemurus (Valenciennes, 1840), a
      popular food fish in Southeast Asia, proved to be infected by 3 myxozoan species.
      All the 3 species belonged to the genus Henneguya: 2 were identified as H.
      mystusia Sarkar, 1985 and H. hemibagri Tchang et Ma, 1993, while the other was
      described as H. basifilamentalis sp. n. All plasmodia were found in the gills and
      were characterised by a specific site selection. H. mystusia formed plasmodia in
      the multi-layered epithelium between the gill lamellae and in the non-lamellar
      edge of the gill filaments, while H. hemibagri developed in the capillary network
      of the lamellae. H. basifilamentalis sp. n. had large oval plasmodia located deep
      among the filaments just above the gill arch.

PMID- 16610588
TI  - Concentrations of erythromycin and azithromycin in mature Chinook salmon
      Oncorhynchus tshawytscha after intraperitoneal injection, and in their progeny.
AB  - A single dose (40 mg kg(-1)) of erythromycin or azithromycin dihydrate was
      injected intraperitoneally into maturing female fall Chinook salmon 12 to 32 d
      before spawning to observe the distribution, retention and clearance of the drugs
      in plasma, kidney, coelomic fluid and egg vitellin, and their persistence in
      alevins derived from these fish. Salmon administered prophylactic dosages of
      erythromycin as subadults were also included to investigate potential interactive
      effects of oral and injected treatments on reproductive performance and
      antibiotic clearance. Erythromycin was rapidly cleared from plasma and coelomic
      fluid, but was detected in the kidney (3.52 to 12.40 microg g(-1)) and egg
      vitellin (5.32 to 8.87 microg ml(-1)) of all fish at spawning. High, stable
      concentrations of azithromycin were detected in plasma (14.66 to 20.33 microg ml(
      1)), kidney (43.16 to 59.96 microg g(-1)), coelomic fluid (2.52 to 5.50 microg
      ml(-1)) and egg vitellin (12.65 to 23.51 microg ml(-1)). Oral administration of
      erythromycin to subadult salmon did not significantly affect tissue
      concentrations of either erythromycin or azithromycin administered by prespawning
      injection. Reductions in the percentage of eggs that yielded live embryos at the
      eyed stage of development occurred among eggs derived from females that had
      received orally administered erythromycin as subadults. Erythromycin was not
      detected in unfed fry derived from adults injected with the drug prespawning, but
      azithromycin was present for more than 2 mo after the onset of exogenous feeding.

PMID- 16610589
TI  - Effects of nitrate and the pathogenic water mold Saprolegnia on survival of
      amphibian larvae.
AB  - We tested for a synergism between nitrate and Saprolegnia, a pathogenic water
      mold, using larvae of 3 amphibian species: Ambystoma gracile (northwestern
      salamander), Hyla regilla (Pacific treefrog) and Rana aurora (red-legged frog).
      Each species was tested separately, using a 3 x 2 fully factorial experiment with
      3 nitrate treatments (none, low and high) and 2 Saprolegnia treatments
      (Saprolegnia and control). Survival of H. regilla was not affected significantly
      by either experimental factor. In contrast, survival of R. aurora was affected by
      a less-than-additive interaction between Saprolegnia and nitrate. Survival of R.
      aurora was significantly lower in the Saprolegnia compared to the control
      treatment when nitrate was not added, but there was no significant difference in
      survival between Saprolegnia and control treatments in the low and high nitrate
      treatments, consistent with increased nitrate preventing Saprolegnia from causing
      mortality of R. aurora. Survival of A. gracile followed a similar pattern, but
      the difference between Saprolegnia and control treatments when nitrate was not
      added was not significant, nor was the nitrate x Saprolegnia interaction. Our
      study suggests that Saprolegnia can cause mortality in amphibian larvae, that
      there are interspecific differences in susceptibility and that the effects of
      Saprolegnia on amphibians are context-dependent.

PMID- 16610590
TI  - Analysis of climatic and geographic factors affecting the presence of
      chytridiomycosis in Australia.
AB  - Chytridiomycosis is an emerging fungal disease that has been implicated in the
      global decline of amphibian populations. Identifying climatic and geographic
      factors associated with its presence may be useful in control and prevention
      measures. Factors such as high altitude, cool temperature, and wet climate have
      been associated with chytridiomycosis outbreaks. Although some of these factors
      have been studied in a laboratory setting, there have been few studies in a
      natural setting. In this investigation, the relationship between altitude,
      average summer maximum temperature, or the amount of rainfall and the presence or
      absence of chytridiomycosis are statistically tested using data from 56 study
      sites in Australia. Currently, in Australia, 48 native species of wild amphibians
      have been found infected with chytridiomycosis. The 56 sites in the present
      study, extending along approximately 50% of the coastline of Australia, have been
      identified as either a chytrid site, where > or = 1 species are infected with
      chytridiomycosis, or a no-decline site, where none of the species present at the
      site are experiencing a decline or are known to be infected. The odds-ratio test
      and two-proportions test applied to this data indicate that the presence of
      chytridiomycosis in Australia is significantly related to temperature. In
      particular, the presence of chytridiomycosis is more likely at sites where the
      average summer maximum temperature is < 30 degrees C. The results of the analyses
      do not indicate a significant relationship between the presence of
      chytridiomycosis and altitude or rainfall.

PMID- 16610592
TI  - Temperature-dependency of Betanodavirus infection in SSN-1 cell line.
AB  - This study examined the in vitro effects of temperature on Betanodavirus
      infection in the SSN-1 cell line. A Betanodavirus isolated from moribund sea bass
      fry Dicentrarchus labrax farmed in the Adriatic Sea and characterised as a RGNNV
      (Redspotted Grouper Nervous Necrosis Virus) genotype was used. Virus-infected SSN
      1 cells were incubated at temperatures between 10 and 30 degrees C and observed
      for cytopathic effects daily for 15 d. Cell-free and cell-associated viral growth
      were evaluated by 50% tissue culture infectious dose (TCID50) titration at 0, 24,
      48, 72, 96, 144, 192, 240, 312 and 360 h post-infection. Virus replication was
      observed at all temperatures from 15 to 30 degrees C. The optimal temperature for
      virus growth was 25 degrees C. A temperature of 10 degrees C was detrimental to
      the growth of the SSN-1 cells and cell death interfered with interpretations of
      viral growth. The isolate of Betanodavirus from Italian sea bass in this study
      demonstrates a different temperature range for growth compared to previous
      reports for related Betanodavirus strains, most likely due to an adaptation to
      the normal environmental temperatures of the host fish species of origin.

PMID- 16610593
TI  - Shell disease: abnormal conchiolin deposit in the abalone Haliotis tuberculata.
AB  - Shell disease in the abalone Haliotis tuberculata L. is characterized by a
      conchiolin deposit on the inner surface of the shell. The gross clinical signs
      appear similar to the Brown Ring Disease (BRD) of clams. BRD has been extensively
      described in clams and is known to be responsible for severe mortalities and the
      collapse of the clam aquaculture industry in western France. In the clam, it was
      found to be caused by the infection of the mantle by Vibrio tapetis. Brown
      protein deposits have been observed in various abalone species around the world;
      some of these have been associated with a fungal infection in New Zealand, but
      the ones described here are similar to bacterial infections observed in clams.
      Larger animals appeared to be more affected by the disease, and a positive
      correlation of the number of successive infections found in the shells with the
      level of infestation of the shell by borers suggests that boring polychaetes and
      sponges may be vectors of the disease, or that the parasite infestation may
      increase the susceptibility of the animal to this infection. There is no
      evidence, however, that this infection causes mortality in abalone.

PMID- 16610594
TI  - [Should the "personality disorders" concept be revised?].

PMID- 16610595
TI  - [Personality disorder traits in childhood and adolescence: concepts,
      methodological approaches and empirical results].
AB  - OBJECTIVE: The practical and theoretical advantages of the diagnosis and
      classification of personality disorder traits in childhood and adolescence remain
      controversial topics, the investigation of which is particularly neglected in
      German-speaking countries. METHOD: This review reports in detail research
      findings on the diagnostic validity and on the stability of personality disorder
      dimensions from childhood and adolescence to adulthood. RESULTS: On the one hand,
      the latest research findings refer to the validity of diagnoses of personality
      disorder in adolescence, and on the other, to the stability of personality traits
      over the course of development. Evidence of the continuity of personality
      disorder traits from adolescence to adulthood, however, is still lacking.
      Dimensional approaches are considered superior with regard to the assessment of
      personality disorder traits, particularly since they reflect development aspects,
      and also due to their higher sensitivity in this respect. CONCLUSIONS:
      Longitudinal studies during both childhood and adolescence are required in order
      to assess the continuity, or the instability, respectively, of dimensionally
      assessed personality profiles and the influence of infant personality factors on
      the development of psychopathology.

PMID- 16610596
TI  - [Aetiology and life-course of conduct disorder in childhood: risk factors for the
      development of an antisocial personality disorder].
AB  - OBJECTIVES: Conduct disorders are among the most common disorders encountered in
      child and adolescent psychiatry. They represent a heterogeneous group of
      disorders, each with a different psychopathology and a different life-course.
      While antisocial behaviour is only transient in some children, others show
      increasing criminal behaviour and delinquency, and some even develop an
      antisocial personality disorder. METHODS: This review presents substantial
      biological and psychosocial factors, as well as their interaction in the
      aetiology of conduct disorders. Changes in autonomic responsiveness are
      emphasized. RESULTS: Especially young children with conduct problems seem to be
      at greater risk for persistent and more widespread antisocial behaviour. Some of
      these children have emotional disturbances similar to those of psychopathic
      individuals. CONCLUSIONS: In order to prevent a negative course of the disorder,
      the relevance of primary care for children at high risk for antisocial behaviour
      is emphasized. In this context, the application of psychophysiological methods
      might be useful, in order to identify these children at an early stage.

PMID- 16610597
TI  - [The effects of the 12th and 14th amendments to the AMG (Medical Preparations
      Act) on paediatric pharmaceutical research--a survey of the new regulations].
AB  - OBJECTIVE: The 12th amendment to the German Medical Preparations Act
      (Arzneimittelgesetz, AMG) implements EU-Directive 2001/20EC in national law and
      introduces changes with regard to academic research in child and adolescent
      psychiatry. The 14th amendment implements labelling regulations for drugs.
      METHOD: This article analyses the effects of these new regulations on safety
      aspects, on the performance of clinical trials with and without sponsoring
      (investigator-initiated trials, IITs), and on the development of paediatric
      drugs. The former regulatory directives are compared with the changes mandated by
      the 12th amendment, and their effects on off-label use, long-term safety, and so
      called dose-finding studies will be pointed out. RESULTS: Current law no longer
      allows post marketing surveillance studies ("Anwendungsbeobachtungen" and
      "Therapieoptimierungsstudien"). Requirements and procedural regulations are now
      standardized for all clinical trials with human beings. The term "group benefit"
      has now been introduced into German law, which excludes research without any
      direct or group benefit for children participating in a study. CONCLUSION: While
      prerequisites for drug development in accordance with GCP guidelines on a high
      medical and ethical standard are now granted, due to multiple regulatory
      requirements, investigator-initiated studies in paediatric psychopharmacology
      will be more difficult to conduct. Moreover, because of the strict regulations,
      it is very improbable that academic research will be undertaken without
      sponsoring (IITs).

PMID- 16610591
TI  - Sequence variation in four mitochondrial genes of the salmon louse Lepeophtheirus
      salmonis.
AB  - A total of 210 Lepeophtheirus salmonis collected from 7 locations (Scotland,
      Russia, Canada, Japan and 3 locations in Norway), were screened for sequence
      variation in 4 mitochondrial genes; ATPase subunit 6 (A6), Cytochrome b oxidase
      subunit I (COI), Cytochrome b (Cyt b) and 16S rRNA. A high level of intraspecific
      variation was observed within all genes. The majority of polymorphisms were
      present in single individuals only, which resulted in a high number of private
      haplotypes within each gene. Little evidence of genetic differentiation was
      observed among the 3 Norwegian locations or between L. salmonis samples from
      Norway, Scotland and Russia. Pairwise FST values indicated that a weak degree of
      sub-division between L. salmonis sampled in Canada and the Northeast Atlantic
      might, however, exist. All samples collected in the Atlantic were highly
      different from the Japanese sample. It is suggested that the lack of genetic
      differentiation among lice samples from the North Atlantic is a result of
      extensive gene flow mediated by passive transport of L. salmonis larvae, and the
      migratory pattern of its salmonid hosts.

PMID- 16610599
TI  - [Do subclinical epileptiform discharges really affect short-term memory in
      children?].
AB  - OBJECTIVE: Deficits in concentration, specific developmental disorders, and
      behaviour problems often impair the educational abilities of children and
      adolescents with epilepsy, even if the subjects are seizure-free. The impact of
      subclinical epileptiform discharges that persist despite adequate antiepileptic
      treatment is not yet understood. Some studies suggest that these lead to
      simultaneous transitory cognitive impairment, thereby affecting short-term memory
      functions. This study examines the impact of subclinical discharges on memory
      functions. METHOD: 40 seizure-free children (10.3 +/- 3.5 years) with subclinical
      epileptiform discharges were examined by means of computerized EEG-coupled tests
      focussing on visuo-spatial and verbal short-term memory, in order to assess the
      temporal relation between discharges and test performance. RESULTS: No
      significant differences in cognitive performance were detected in phases with and
      without epileptiform discharges; neither discharges > 1.5 sec, nor multiple
      discharges within a test impaired performance. Moreover, performance was
      independent of the localisation of discharges and of the time of their occurrence
      during the test. CONCLUSIONS: The present study showed no association between
      subclinical epileptiform discharges and error rates as indicators of transient
      cognitive impairment in visuo-spatial and verbal short-term memory. Hence, other
      mechanisms have to be taken into account to explain the known cognitive deficits
      in patients with epilepsy.

PMID- 16610598
TI  - [Temperament and character profiles of female adolescent patients with anorexia
      and bulimia nervosa].
AB  - OBJECTIVE: Based on the personality model outlined by Robert C. Cloninger,
      studies in adult patient samples demonstrated that according to distinct
      personality profiles patients with anorexia nervosa could be differentiated from
      those with bulimia nervosa, as well as from healthy controls. The current study
      examines whether these personality-related differences also exist in adolescent
      patients with eating disorders and a short duration of illness. METHOD: The
      sample studied consists of 73 consecutively admitted female patients aged 12 to
      18 years, with eating disorders. The German version of the Junior Temperament and
      Character Inventory (JTCI) was administered to 29 patients with anorexia nervosa,
      restricting type (AN-R), to 16 patients with anorexia nervosa, binge
      eating/purging type (AN-B), and to 28 patients with bulimia nervosa (BN).
      RESULTS: Different temperamental factors were most pronounced between AN-R and BN
      patients, whereas AN-B patients exhibited a personality profile between those of
      AN-R and BN. BN patients scored higher on Novelty Seeking but lower on
      Persistence than AN-R patients. In contrast to AN-R patients, both BN and AN-B
      patients scored lower on Self-Directedness. CONCLUSIONS: The current results of
      differential temperamental dimensions in adolescent patients with eating
      disorders tended to be similar to findings for adult patients, which strengthens
      the assumption that distinct personality factors underlie the different subtypes
      of eating disorders.

PMID- 16610600
TI  - Building bridges in wound management.

PMID- 16610601
TI  - New nursing era may prove detrimental.

PMID- 16610602
TI  - How to solve the nursing shortages.

PMID- 16610603
TI  - Poor service from recruitment agencies.

PMID- 16610604
TI  - Recovering from surgery at home--challenges for older people.

PMID- 16610605
TI  - Easing the pressure of wound care.

PMID- 16610606
TI  - Bridging gaps in wound care.

PMID- 16610607
TI  - Treating wounds with oxygen.

PMID- 16610608
TI  - The nursing role in oxygen treatment.

PMID- 16610609
TI  - Lobbying MPs is important work.

PMID- 16610610
TI  - Surgical bus serves communities and enhances the skills of rural nurses.

PMID- 16610611
TI  - What are the attractions of surgical nursing?

PMID- 16610612
TI  - Valuing the expertise of enrolled nurses.

PMID- 16610613
TI  - Valuing caregivers and hospice nurses.

PMID- 16610614
TI  - [Metabolic syndrome in childhood and adolescence].
AB  - Metabolic syndrome has an outstanding impact on public health due to its
      increasing prevalence and poor prognosis. The development of insulin resistance,
      as a consequence of obesity, can be demonstrated even in childhood which has a
      pivotal role in the pathomechanism of the syndrome. Besides obesity, low birth
      weight, increased gain in body mass in early childhood, decreased pubertal
      insulin sensitivity and clinical markers of insulin resistance (acanthosis
      nigricans, polycystic ovarian syndrome, premature adrenarche) confer risk of
      metabolic syndrome. Currently, there are no consistent and consensus based
      diagnostic criteria of metabolic syndrome in children and adolescents. The most
      recent definition of the International Diabetes Federation [central obesity plus
      any two of four factors (raised triglyceride, reduced high-density lipoprotein
      cholesterol, raised blood pressure and raised fasting plasma glucose)] is not
      approved for children and epidemiology data are not yet available. Applying the
      modified version of the most commonly used Adult Treatment Panel III diagnostic
      system for children and adolescents, the prevalence is given as 4.2% in the
      literature. As the components of the syndrome, frequency were as follows: 9.8
      17.9% for abdominal obesity, 21.0-23.4% for elevated triglyceride, 18.3-23.3% for
      reduced high-density lipoprotein-cholesterol, 4.9-7.1% for elevated blood
      pressure and 0.8-1.7% for impaired fasting glucose. High frequency of
      morphological and functional disturbances of the vascular and endothelial systems
      seen frequently among children with signs of metabolic syndrome suggests early
      cardiovascular events and underlines the clinical significance of this entity.
      The most effective tool for prevention of metabolic syndrome is to avoid the
      development of childhood obesity. In case of established disease, the effective
      treatment should address the different components of the syndrome. The authors
      emphasize the need of elaboration of consensus based pediatric diagnostic
      criteria, national prevalence data, protocols for prevention, early recognition
      and effective treatment.

PMID- 16610615
TI  - [The role of transmembrane lipidtransporter molecules in the atherosclerotic
      process].
AB  - The role of transmembrane lipidtransporter molecules in the atherosclerotic
      process. The protective effect of high-density lipoprotein in the atherosclerotic
      process has been mainly attributed to its role in reverse cholesterol transport.
      Identification of mutations in the ATP-bindig casette transporter-A1 (ABCA1) as
      the genetic defect in genetic high-density lipoprotein-deficiency (Tangier
      disease) and selected patients with familiar hypoalphalipoproteinemia has
      generated interest in discovering the role of this lipid transporter molecule in
      the reverse cholesterol transport. It is well established, that the ABCA1
      mediates cellular cholesterol efflux through transfer of phospholipids and
      cholesterol from the inner to the outer layer of the cell membrane, thus enabling
      the bindig to apolipoproteins. Previous studies showed that the ABCA1 is
      critically involved in cellular trafficking of cholesterol and phospholipids in
      total body of lipid homeostasis. In Tangier disease, the loss of the function of
      ABCA1, leads to an impaired formation of nascent high-density lipoprotein
      particles by preventing the release of cellular phospholipids and cholesterol to
      the acceptor apolipoprotein A1. This rare genetic disorder is characterized by a
      severe high-density lipoprotein deficiency, cholesterol deposition in macrophages
      and premature atherosclerosis. These findings implicate the ABCA1 as an important
      therapeutic target for preventing diseases that are associated with accelerated
      atherogenesis. The present review summarizes the current knowledge of the ABCA1,
      its pivotal role in the cholesterol homeostasis and preventing atherosclerosis.

PMID- 16610616
TI  - [Azathioprine-associated interstitial pneumonitis].
AB  - Azathioprine-associated interstitial pneumonitis. The early hypersensitivity
      reaction and the late bone marrow depression are well known side effects of the
      azathioprine; the interstitial pneumonia is a rare complication. A 40-year old
      male patient was treated with azathioprine due to extensive ulcerative colitis
      for ten years. He complained seven days of fever, cough and catarrhal signs,
      without the symptoms of active colitis. The opportunistic infections were ruled
      out. Chest X-ray, CT and lung biopsy proved the presence of interstitial
      inflammation. The azathioprine therapy was discontinued as the potential source
      of the pulmonary infiltrate. As a result of steroid therapy, as well as emergency
      unit care, the pulmonary infiltrates decreased gradually. Three months later his
      ulcerative colitis relapsed, for this an ileo-anal pouch surgery was done. In
      case of atypical pneumonia, without proven opportunistic infection, azathioprine
      associated interstitial pneumonitis may be present, which heal after cessation of
      the drug.

PMID- 16610617
TI  - [Assessment of suicidal behaviour in general practice].
AB  - AIM: To assess the prevalence of suicidal behavior (wish to die, suicidal
      thoughts, suicide attempts) and to determine the characteristics of suicide
      attempters in primary care, including screening for major mental disorders.
      METHOD: A Hungarian urban general practitioner's district with 1248 inhabitants
      was screened for suicidal behavior as well as for major mental disorders. All the
      patients (n=382) who visited their general practitioner within a two-week period
      were asked to participate. 277 patients completed the Prime-MD questionnaire, an
      easy-to-use diagnostic instrument developed for general practitioners to
      recognize the most common psychiatric disorders, like depressive (major
      depressive disorder, minor depressive disorder), anxiety (panic disorder,
      generalized anxiety disorder), somatoform, eating and alcohol related disorders.
      Detailed data about suicidal thoughts and attempts were also collected by the
      structured questions of MINI-Plus diagnostic interview. RESULTS: Prevalence of
      suicide attempts in primary care was 2.9%. 9% of the patients had either suicidal
      thoughts or suicide attempts in the previous month. Suicidal patients were more
      ready to use psychotropic drugs, they assessed their health status more poorly,
      and had more mental symptoms than the control group (non-suicidal patients). 60%
      of suicidal patients and 11.5% of the investigated population had a current
      depressive episode. Beside depressive symptoms, anxiety disorders and alcohol
      problems were also more common among suicidal patients. The rate of previous
      psychiatric treatments was also higher in suicidal patients, who generally
      visited their general practitioners less frequently than non-suicidal patients.
      According to multivariate logistic regression, suicidal patients are more ready
      to take antidepressants, they tend to have more previous psychiatric treatments
      and suicidal attempts, and they visit their general practitioners less frequently
      and have a current depressive episode. CONCLUSION: Suicidal behavior and mental
      disorders are frequent in primary care. Since almost every tenth patient visiting
      their general practitioner has suicidal thoughts or depressive or anxiety
      disorder, the recognition of suicide risk and mental disorders is very important
      in primary care. As for preventing suicides, the diagnosing and treating of
      mental disorders -especially affective disorders- are very important for general
      practitioners. In addition to pharmacotherapy, psychotherapies are also important
      in treating patients in crisis situations, or with suicidal thoughts or
      depressive disorder. The modified Prime-MD questionnaire can be an effective,
      easy-to-use method in the hand of the general practitioners to identify suicidal
      risk and to recognize the most common mental disorders in the average population.

PMID- 16610618
TI  - [A proposed new interpretation and revised definition of perinatal mortality].
AB  - A proposed new interpretation and revised definition of perinatal mortality.
      Perinatal mortality rate is a commonly used index, which reflects the quality of
      obstetrical and neonatological care. Relying on critical remarks considered for
      his study, the author believes that a novel classification should be developed in
      order to redefine the term perinatal mortality and pregnancy-related losses. The
      author points out that intrauterine death during pregnancy cannot be associated
      with fatal incidents about birth, because the former precedes the latter. While
      regarding the cases of intrauterine death at late pregnancy as being important
      specific indicators, the author proposes excluding them from the cases covered by
      the term perinatal mortality. Furthermore, the author argues that all cases of
      neonatal death, that is, those at birth and those occurring in the first 28 days
      of life should be regarded as cases of perinatal mortality. It is reasonable to
      extend perinatal period this way, because due to a more advanced neonatological
      care, immature preterm babies may be lost 6 or even 27 days after birth. A novel
      interpretation of perinatal mortality, not including the cases of intrauterine
      death at late pregnancy, but including all cases of neonatal mortality makes
      perinatal mortality rate a more exact qualifier of obstetrical and neonatological
      care.

PMID- 16610619
TI  - [In memoriam Jeno Kiraly, chief surgeon of Sopron, Hungary].

PMID- 16610620
TI  - [Thoughts about Csaba Lentner's book entitled Political change and politics of
      finance, published by the Akademia Publishing Company in 2005].

PMID- 16610621
TI  - [Chromatographic mass spectrometric determination of low-molecular-weight
      aromatic compounds of microbial origin in the serum from patients with sepsis].
AB  - The investigation quantitatively determined the content of low-molecular-weight
      aromatic compounds of microbial origin in the sera of 34 individuals by
      chromatographic mass spectrometry. An "Agilent Technogies 6890N" gas
      chromatograph with a 5973 mass selective detector was applied; chromatographic
      separation of components was effected on an Hp-5MS quartz capillary column.
      Aromatic small molecules originating from microbes (SMOM) were determined in the
      sera of 7 patients with sepsis. The diagnosis of sepsis was documented by the
      presence of the systemic inflammation syndrome and by that of bacteriemia and/or
      artificial ventilation-associated pneumonia along with the level of procalcitonin
      of higher than 10 ng/ml. The levels of aromatic SMOM were compared in 10 healthy
      donors, 8 preoperative cardiosurgical patients, and 9 patients with different
      abnormalities without sepsis treated in an intensive care unit (ICU). Serum
      phenylacetic and 3-phenylpropionic acids were found to be prevalent in the
      healthy donors and postoperative cardiosurgical patients. In ICU patients with
      different complications without sepsis, more than half the compounds under study
      were undetectable, the others were found in very low concentrations, which may be
      accounted for by antibiotic therapy. At the same time, almost the whole spectrum
      of the test compounds (other than 3-phenylpropionic acid) with the highest
      concentrations of 3-phenyllactic, p-hydroxyphenylacetic, 3-(p
      hydroxyphenyl)lactic and 2-hydroxybutanic acids, was detectable in septic
      patients receiving a more intensive therapy. The differences were statistically
      significant (by the Mann-Whitney U-test; p < 0.05). By taking into account the
      potentially high biological activity of the test compounds, studies are to be
      continued in this area.

PMID- 16610622
TI  - [Membrane lipids in patients with chronic bronchitis concurrent with urolithiasis
      in the phase of clinical remission].
AB  - The composition of erythrocytic lipids was studied in patients with chronic
      nonobstructive bronchitis in the phase of clinical remission concurrent with
      urolithiasis. There was a significant increase in the proportion of
      phosphatidylserine with the decreased levels of sphingomyelin and
      phosphatidylcholine, a reduction in the relative quantity of fatty acids of iso-
      and anteisometric structure, an impairment in the relations between fatty acids
      that are precursors of the synthesis of eicosanoids of different series, as well
      as a decrease in the total unsaturation of erythrocytic lipids. The impairments
      found in the composition of erythrocytic lipids are markers of membrane
      destruction and they may serve as diagnostic criteria for concomitant pulmonary
      and renal lesions.

PMID- 16610623
TI  - [Diagnostic value of neopterin in viral infection of patients with the
      transplanted heart].

PMID- 16610624
TI  - [The redox potential of blood and the competence of the antioxidative defense
      system in pregnant females with cytomegalovirus infection].

PMID- 16610625
TI  - [Determination of serum fucosidase activities].
AB  - A method has been developed for simultaneous determination of the activity of
      alpha-L-fucosidase (EC 3.2.1.51) and the beta-D-fucosidase activity induced by
      beta-D-galactosidase (IV, EC 3.2.1.23) in the serum. The paper presents data on
      changes in these enzymatic activities in the serum in an experiment, in acute
      hematogenous osteomyelitis and recurrent laryngotracheitis in children in
      pregnant females with gestosis and placental insufficiency.

PMID- 16610626
TI  - [Procedure for calculating the index of low- and medium-molecular-weight
      substances in the serum].

PMID- 16610627
TI  - [HPLC analysis of urinary metabolites of catecholamines and serotonin for routine
      laboratory practice].
AB  - A simple high performance liquid chromatographic technique has been developed to
      analyze urinary metabolites of catecholamines along with ultraviolet detection.
      The metabolites were extracted in ethyl acetate when a biospecimen was saturated
      with ammonium sulfate. Separation was effected on a column containing 5 microm of
      Diasphere C16 in the two-stage low-pressure gradient. The eluents were based on
      acetonitrile-isopropanol-0.02 M citric acid, added by potassium perchlorate, 5
      g/l (3 and 10% of its organic phase). The complete chromatographic cycle was
      about 30 min. The extraction degree was 86-106%. The sensitivity (detection
      limit) of the technique at a signal/noise ratio of > 3 was 2 ng (vanilylmandelic
      acid), 3 ng (iso-vanilylmandelic acid) and 3,4-dioxyphenylacetic acid), 1 ng (5
      hydroxyindoleacetic acid), and 5 ng (homovanillic acid). The linear dependence
      was in the range of 5 to 1,000 ng. The author presents his own findings and the
      data available in the literature on the content of metabolites of catecholamines
      and serotonin in healthy individuals and in patients with catecholamine-secreting
      tumors (pheochromocytoma and neuroblastoma).

PMID- 16610628
TI  - [An association with the values of homocystein with the course of a postinfarct
      period in patients of different age].

PMID- 16610629
TI  - [Genetic polymorphism of glutathione-S-transferase M1 and T1 in children with
      acute lymphoblastic leukemia].
AB  - Children with acute lymphoblastic leukemia (ALL) and deletions of glutathione-S
      transferase M1 (GSTMI) and glutathione-S-transferase T1 (GSTT1) have better event
      free survival and lower rates of relapses than those with GSTM1 and/or GSTT1. It
      is concluded that deletions of GSTM1 and/or GSTT1, double-null genotype are
      closely associated with the good prognosis of childhood ALL treated according to
      the ALL-BFM 90 and ALL-MB 91 protocols.

PMID- 16610630
TI  - [Pathophysiology of carbohydrate metabolism (a lecture)].

PMID- 16610631
TI  - [Neutrophilic functional heterogeneity].
AB  - Blood neutrophilic functional heterogeneity is under discussion. The neutrophils
      of one subpopulation, namely killer neutrophils (Nk), potential phagocytes,
      constitute a marginal pool and a part of the circulating pool, intensively
      produce active oxygen forms (AOF) and they are adherent to the substrate. The
      neutrophils of another subpopulation, cager neutrophils (Nc), seem to perform a
      transport function of delivering foreign particles to the competent organs, to
      form about half of the circulating pool, to produce APC to a lesser extent,
      exclusively for self-defense and, probably, in usual conditions, to fail to
      interact with substrate. Analysis of the experimental findings suggests that the
      phylogenetic age of Nk is older than that of Nc and Nk has predominantly a
      tendency to spontaneous apoptosis under physiological conditions.

PMID- 16610632
TI  - [Differential trypan blue staining of tumor cells for the determination of
      apoptosis].
AB  - The present paper suggests that trypan blue should be used for differential
      staining of tumor cells in order to determine apoptosis. The proposed method
      makes it possible to simplify operations, to reduce the time required to carry
      out a test, and to enhance the precision of determining the course of apoptosis
      during routine investigations. The paper also gives data of the comparative
      studies of the content of apoptotic cells in experimental melanoma B-16 though
      differential trypan blue staining and classical morphostructural analysis. The
      difference in the values obtained by these two methods is shown to be 35%.

PMID- 16610633
TI  - [Clinical trials of the prototype of commercial two-phase nutrient medium for
      hemoculture isolation].

PMID- 16610634
TI  - [The laboratory standards of medical care].

PMID- 16610635
TI  - A quantitative ultrastructural study of the liver and the spleen in fatal
      falciparum malaria.
AB  - We performed a retrospective study of 25 patients who died of severe falciparum
      malaria in Thailand and Vietnam using electron microscopy. The aims of the study
      were: to determine if there was any significant association between parasitized
      red blood cells (PRBC) sequestered in liver and spleen and particular pre-mortem
      clinical complications, and to compare the degree of parasite load between the
      liver and spleen within the same patients. PRBC sequestrations in each organ were
      compared with the pre-mortem parasitemia, to calculate the sequestration index
      (S.I.). The S.I. showed that the degree of PRBC sequestration in the spleen was
      higher than the liver (S.I. median = 3.13, 0.87, respectively) (p < 0.05). The
      results of quantitative ultrastructural study showed a significantly high
      parasite load in the liver of patients with jaundice, hepatomegaly and liver
      enzyme elevation (p < 0.05). We found a significant correlation between PRBC
      sequestration in the liver and a high serum bilirubin level, a high aspartate
      aminotransferase (AST) level and an increase in the size of the liver (Spearman's
      correlation coefficient = 0.688, 0.572, 0.736, respectively). Furthermore, a
      higher parasite load was found in the liver of patients with acute renal failure
      (ARF) compared to patients without ARF (p < 0.05). These findings suggest that
      PRBC sequestration in the liver is quantitatively associated with pre-mortem
      hepatic dysfunction and renal impairment. There was no significant difference
      between splenomegaly and PRBC sequestration. The size of a palpable spleen was
      not correlated with parasite load in the spleen. When ultrastructural features
      were compared between the two reticuloendothelial organs, we found that the
      spleen had more PRBC and phagocytes than the liver. The spleen of non-cerebral
      malaria (NCM) patients had more phagocytes than cerebral malaria (CM) patients.
      This observation reveals that the spleen plays a major role in malaria parasite
      clearance, and is associated with host defence mechanisms against malaria.

PMID- 16610636
TI  - Study on cyclospora cayetanensis associated with diarrheal disease in Nepal and
      Loa PDR.
AB  - A study of diarrheal diseases associated with Cyclospora cayetanensis was
      conducted in Nepal and Lao PDR. A total of 2083 samples were included in this
      study. Samples in Nepal were collected from October 1999 to August 2002 whereas
      samples in Lao PDR were collected from February 2002 to June 2003. C.
      cayetanensis was detected by direct microscopy using ultraviolet and differential
      interference contrast microscopy. The overall positive rate in Nepal was 9.2%
      (128/ 1397). A higher positive rate was observed in children aged 10 years and
      under (11.1%) and was lowest in the age group of 51-60 years (3.1%). A
      significantly higher positive rate was observed in the summer (rainy season)
      (12.6%) with the lowest prevalence in the spring (dry season) (1.8%) (p < 0.05).
      The positive rate was closely associated with rainfall (ml/month). Interestingly,
      only one of the total 686 samples (0.1%) from Lao PDR was found to be positive
      for Cyclospora oocysts.

PMID- 16610637
TI  - Comparison of five DNA extraction methods and optimization of a b1 gene nested
      PCR (nPCR) for detection of Toxoplasma gondii tissue cyst in mouse brain.
AB  - Toxoplasmosis, caused by Toxoplasma gondii, is an important parasitic disease
      worldwide. Different techniques have been developed for T. gondii detection. At
      present, polymerase chain reaction (PCR) has been widely used. However, PCR for
      identifying T. gondii remains unsatisfactory in many laboratories because of lack
      of standardization and variations in efficiency. In the present study, we
      optimized a nested PCR protocol (n-PCR) in order to compare the amplification of
      T. gondii DNA, after being extracted from mouse brain by five different DNA
      extraction methods including phenol chloroform, QIAamp DNA minikit, Genomic DNA
      purification kit and Chelex with or without proteinase K. All DNA extraction
      methods were able to extract DNA from a single tissue cyst from mouse brain.
      However, among the five DNA extraction methods, the Chelex without proteinase K
      appeared to be the most rapid and easiest.

PMID- 16610638
TI  - Development of the rapid and simple elisa (whole blood-ELISA) using coconut water
      tween as a wash solution for whole blood sample from Schistosoma japonicum
      infected rabbit and human.
AB  - PBS-Tween as a wash solution, prepared with distilled water, is used in ELISA. In
      areas where schistosomiasis is endemic, however, distilled water is hard to come
      by. We have modified a WHOLE BLOOD-ELISA test to use coconut water-Tween as a
      wash solution, because coconut water is easy to come by and cheap in the tropics.
      We applied the test to whole blood samples from rabbits and humans infected with
      Schistosoma japonicum. This modified WHOLE BLOOD-ELISA was confirmed to be a
      rapid, simple, and cost-effective method.

PMID- 16610639
TI  - Effects of a school-based education program for schistosomiasis control.
AB  - The role and effect of school-based education for schistosomiasis control needs
      to be explored further to raise the standard of health in the widely infected
      areas over the world. This study investigated the effect, particularly the
      retention or duration of effect, of a school education program for
      schistosomiasis control. The study was conducted from September 2000 to February
      2001 in a district of Mount Darwin, Zimbabwe. Two hundred ninety-nine fifth
      graders from 8 primary schools were examined for their knowledge, attitude,
      beliefs and practice regarding schistosomiasis, based on a KABP form, three times
      in succession. The examinations were a baseline examination, a pre-examination
      checking for the effect of the program, and a post-examination assessing
      retention after three-months. Analyses of the examination results indicated a
      considerable effect of the program in all aspects except for practice. Further
      detailed analyses on 161 matched pair subjects comparing the difference between
      the pre- and post-examination results demonstrated how the subjects maintained or
      rather increased what they had learned, illustrating an amplifying resonance or
      percussion effect, that is, a group dynamic effect in the school setting. No
      clear correlation, however, was shown between the education effect and the
      infection rate of the subject groups. Ways to prevent the deterioration of the
      practice aspect, and the cause of the negative correlation between the infection
      rate and education effect need to be closely investigated, while trying out more
      participatory-type education is an absolute necessity.

PMID- 16610640
TI  - Phenotypical characterization of intestinal Schistosoma japonicum granulomas in
      pigs.
AB  - The pig has been proposed as a model for human schistosomiasis japonica and the
      use of this animal model is increasing. The inflammatory response to schistosome
      infection in the liver and intestine of the pig shows morphological differences,
      and only the hepatic granulomas have been phenotypically characterized. The aim
      of the present study was to phenotypically characterize the cellular inflammatory
      response in the cecum by immunohistochemistry with particular reference to
      perioval granulomatous reactions in Schistosoma japonicum infected pigs. Six pigs
      were exposed to 2000 cercariae and examined 9 weeks post-infection. Three
      uninfected pigs of the same age served as controls. Exposed pigs developed patent
      infections with the total number of worms between 6 and 110. Cecal granulomas
      were dominated by CD3 positive T-lymphocytes and IgG positive plasma cells.
      Despite the difference in the inflammatory response between the liver and the
      cecum, the results from this study indicate that the phenotypic cellular
      composition of cecal granulomas appears similar to what has previously been
      described in the liver.

PMID- 16610641
TI  - The high prevalence of asymptomatic Toxocara infection among schoolchildren in
      Manado, Indonesia.
AB  - We performed a serological survey of Toxocara canis infection in junior high
      school students from three districts in northern Sulawesi. Almost all of the 117
      subjects from two rural districts near Manado allowed dogs in their houses, and
      there was an 84.6% prevalence of T. canis infection in this group. Fifty-three
      subjects (45.3%) had serum samples with a high titer of specific anti-Toxocara
      antibody. By contrast, 41 students tested in one urban district showed a 12.2%
      prevalence. To confirm the clinical symptoms of visceral larva migrans (VML) and
      ocular larva migrans (OLM) caused by Toxocara, we administered a questionnaire
      survey, serological liver function tests, and an ophthalmoscopic examination in
      34 subjects having high anti-Toxocara antibodies. One rural district showed a
      high prevalence; 58 out of 71 subjects (81.7%) had a high titer of anti-Toxocara
      antibodies according to a plate-ELISA test, although none showed clinical signs.
      Five of these subjects exhibited hypereosinophilia. These results indicated that
      T. canis infection in northern Sulawesi is latent in many more cases than
      previously estimated, and suggest that people living in environments polluted by
      Toxocara eggs become easily infected with T. canis and show a high prevalence of
      infection.

PMID- 16610642
TI  - Intestinal parasitic infections in schoolchildren in a suburban area of Hanoi,
      Vietnam.
AB  - An epidemiological study on intestinal parasitic infections among schoolchildren
      in a suburban area of Hanoi, Vietnam, was conducted. Of the 217 schoolchildren
      involved in this study, 166 (76%) were positive for at least one of nine species
      of parasite (six helminths and three protozoa). Among the helminth parasites,
      Trichuris trichiura (67%) was detected the most frequently followed by Ascaris
      lumbricoides (34%) and hookworm (3%). In the case of protozoan parasites,
      Entamoeba coli (8%) was the most frequently detected followed by E. histolytica
      (2%). No Cryptosporidium parvum or Cyclospora sp were found. A questionnaire
      survey revealed that there was no positive relationship between parasite
      infection and the children's school records, educational background or parental
      income, which have been known to play a role.

PMID- 16610643
TI  - Screening for larvicidal activity in some Thai plants against four mosquito
      vector species.
AB  - Ninety-six ethanolic extracts from various parts of 84 Thai plant species were
      tested for their larvicidal activity against Aedes aegypti mosquitoes. Extracts
      from Rhinacanthus nasutus, Derris elliptica, Trigonostemon reidioides, Homalomena
      aromatica, Stemona tuberosa and Acorus calamus possessed high larvicidal
      activity, with LC50 values between 16.0 and 48.2 mg/l. Petroleum ether (PE) and
      methanol (MeOH) extracts were tested for their larvicidal activity against 4
      mosquito vector species. The PE extract of R. nasutus exhibited larvicidal
      effects against Ae. aegypti, Culex quinquefasciatus, Anopheles dirus and Mansonia
      uniformis with LC50 values between 3.9 and 11.5 mg/l, while the MeOH extract gave
      LC50 values of between 8.1 and 14.7 mg/l. D. elliptica PE extract showed LC50
      values of between 11.2 and 18.84 mg/l and the MeOH extract exhibited LC50 values
      between 13.2 and 45.2 mg/l.

PMID- 16610644
TI  - Efficacy of repellent products against caged and free flying Anopheles stephensi
      mosquitoes.
AB  - The efficacy of 9 repellents (8 commercial repellents and one product under
      development) was evaluated on the skin at dosages of 0.65 and 1.7 mg of
      product/cm2, the latter dosage being the industrial standard for deet based
      repellents. The repellents were applied to the arm or lower leg of a human
      subject and tested against Anopheles stephensi in a cage or flying freely in a
      mosquito-proof room. In the cage tests, a product with 20% p-menthane-3, 8-diol
      (PMD) active ingredient provided complete repellency for 7-8 hours, while with
      10% PMD had complete repellency for only 30 minutes. The natural oils of clove
      (Syzygium aromaticum) (10% active ingredient) plus makaen (Zanthoxylum limonella)
      (10% active ingredient) gave protection for 4-5 hours. In the case of free flying
      mosquitoes, products with 20% and 30% PMD gave complete protection for 11-12
      hours at a dosage of 1.7 mg/cm2 or 6 hours at half the dosage, while the product
      with 10% PMD afforded protection for less than 2 hours. At the higher dosage rate
      40% citronella and hydroxyethyl isobutyl piperidine carboxylate, a new synthetic
      compound, provided complete repellency for 7 hours. Fifty percent deet (N,N
      diethyl-3-methylbenzamide) was effective for 30 hours if left undisturbed on the
      skin.

PMID- 16610645
TI  - Clinical differences among PCR-proven dengue serotype infections.
AB  - The objective of this study was to compare the clinical spectra of the dengue
      serotypes proven by the PCR technique. This retrospective study reviewed the
      clinical information of dengue-infected patients who were admitted to
      northeastern provincial hospitals in Thailand from June to September 2002. Dengue
      infection and viral serotypes were confirmed by polymerase chain reaction (PCR).
      Paired anti-dengue immunoglobulin G (IgG) and IgM from paired sera were analyzed
      by enzyme-linked immunosorbent assay (ELISA). Ninety-nine PCR-proven dengue
      infected Thai patients were studied. Their ages ranged from 3-30 years. They were
      infected with DEN1, DEN2, DEN3 and DEN4 in 21, 55, 12, and 12%, respectively.
      Twenty-two percent had primary and 78% had secondary infections. Dengue fever was
      the most common presentation for both primary (77.2%) and secondary infections
      (46.7%). The ratios of dengue fever:dengue hemorrhagic fever (DF:DHF) and non
      dengue shock syndrome:dengue shock syndrome (non-DSS:DSS) for DEN2 was the lowest
      of the dengue serotypes. There was no difference in the duration of fever,
      percentage of hepatomegaly and bleeding among the serotypes in both DF and DHF.
      The trends in the white blood cells, lymphocyte and atypical lymphocyte counts in
      DEN3 were the highest, while those of DEN1 were the lowest of the dengue
      serotypes.

PMID- 16610646
TI  - Community-based approach for prevention and control of dengue hemorrhagic fever
      in Kanchanaburi Province, Thailand.
AB  - An action research design was conducted in two villages of Mueang District,
      Kanchanaburi Province to assess the effectiveness of a community-based approach
      program. Knowledge, perceived susceptibility, self-efficacy, and regular larval
      survey behavior were measured for program outputs. Container Index (CI), House
      Index (HI), and Breteau Index (BI) were used to confirm program outcomes. Key
      community stakeholders in the experimental village were identified and empowered
      through active learning in the village. Monthly meetings with the key
      stakeholders were used to share experiences learned, to reflect on the program
      outputs and outcomes as well as to plan for the next cycle of program activities.
      The program was quite successful. Knowledge, perception, self-efficacy, and
      larval survey practices in the experimental group were significantly higher than
      before the experiment, and higher than the comparison group. CI, HI, and BI were
      decreased sharply to better than the national target. Community status as
      community leaders was the best predictor for larval survey behavior at the first
      survey. Participating in the study program activities was the best predictor at
      the end of the program. The results from this study suggest that the dengue
      hemorrhagic fever (DHF) prevention and control program at the sub-district health
      level should be more proactive and emphasized at the village level. Monitoring
      the disease control program outputs and outcomes should be performed regularly
      during monthly meetings. Finally, local health officers need to be empowered for
      these matters.

PMID- 16610647
TI  - Varicella epidemiology and cost-effectiveness analysis of universal varicella
      vaccination program in Taiwan.
AB  - Varicella zoster virus is highly contagious and affects people worldwide. In this
      study, we collected local epidemiological data and evaluated the cost
      effectiveness of varicella vaccination program in Taiwan. To examine the
      economical consequences of universal vaccination, a model of the incidence and
      the associated costs in a hypothetical cohort was created each year for 30 years.
      The incidence increased sharply after the infancy and peaked in children aged 5
      years. The hospitalization rate among cases was the highest in infants, followed
      by adults 30 to 44 years old. The benefit-cost analysis showed that one dollar
      invested in the program would cost extra 46 cents in direct medical expense, but
      would save extra 45 cents considering the societal expenses. Substantial
      economical benefits can occur due to the averted unproductive days for parents.
      Sensitive surveillance of both varicella and zoster is essential in countries
      that have implemented or are about to implement varicella vaccination.

PMID- 16610648
TI  - Oral and constitutional manifestations of HIV-infected hospital patients in
      Northern Vietnam.
AB  - This study reports clinical features, with emphasis on oral lesions and
      constitutional signs, of 170 patients in a regional hospital in northern Vietnam,
      of whom 56 were HIV positive. The purpose of the study was to investigate the
      relationship of oral hairy leukoplakia (OHL) and oropharyngeal candidiasis (OPC)
      with HIV infection and late stage HIV disease. Late stage HIV disease was defined
      as WHO stage III or IV and/or a total lymphocyte count below 1200 cells/mm3. The
      56 HIV positive patients included all patients with a positive HIV test between
      July 7th and September 9th 2002. A total of 114 HIV negative controls were
      included as well. All patients had a detailed medical history and examination as
      well as a thorough oral examination, which were all done without prior knowledge
      of the patient's HIV serostatus. HIV positive patients were then grouped
      according to WHO clinical stage and total lymphocyte count. Thirty-six patients
      (64.3%) out of 56 HIV positives were in WHO stage III+IV and 28 patients (50.0%)
      had a total lymphocyte count below 1200 cells/mm3. The presence of OPC, weight
      loss of more than 10% of body weight and/or chronic fever of more than one
      month's duration showed a significant association and high positive prediction
      with HIV infection, especially late stage HIV disease [all with odds ratio (OR)
      and 95% confidence interval (CI > 1)]. The presence of OHL only showed a
      significant association with positive HIV serostatus and WHO stage III+IV. It can
      be concluded that in North Vietnam, HIV positive patients and patients suspected
      of having HIV infection would benefit from initial and repeat oral examinations.
      OPC, together with other signs of progressive infection (constitutional signs,
      such as weight loss and chronic fever) may serve as indicators for institution of
      prophylactic drugs against opportunistic infections and even antiretroviral (ARV)
      therapy, when available. However, further research is needed to demonstrate the
      role of OHL in HIV patients in North Vietnam.

PMID- 16610649
TI  - Clinical features, etiology and short term outcomes of interstitial pneumonitis
      in HIV/AIDS patients.
AB  - A prospective study was conducted at Bamrasnaradura Hospital, Nonthaburi
      Province, Thailand from November 11, 2002 to January 5, 2003. A total of 59
      HIV/AIDS patients with interstitial infiltrates on chest radiographs were
      included in the study. The objectives of this study were to describe the clinical
      manifestations and determine the etiologies of interstitial pneumonitis, assess
      the short-term outcomes and determine the accuracy of the clinical diagnosis of
      the etiologies of interstitial pneumonitis in HIV/AIDS patients at Bamrasnaradura
      Hospital, Nonthaburi, Thailand. Tuberculosis was the most common diagnosis (44%),
      followed by Pneumocystis carinii pneumonia (25.4%), bacterial pneumonia (20.3%)
      and fungal pneumonia (10.2%). In tuberculosis, compared to other diagnoses, a
      mild cough (p = 0.031), pallor (p = 0.021), lymphadenopathy (p < 0.001), absence
      of skin lesions (p = 0.003), higher mean body temperature (p = 0.004) and an
      absence of dyspnoea on exertion (p = 0.042) were significant findings. On
      multivariate analysis, however, only an absence of skin lesions (p = 0.023)
      remained a statistically significant predictor of TB. In Pneumocystis carinii
      pneumonia compared to other diagnoses, dyspnea on exertion (p = 0.014), non
      purulent sputum production (p = 0.047), a higher mean respiratory rate (p <
      0.001), absence of lymphadenopathy (p < 0.001) and lack of purulent sputum (p =
      0.030) were significant factors. By multivariate analysis, only an absence of
      lymphadenopathy were shown to be independently and statistically significantly
      associated (p = 0.040). In bacterial pneumonia, compared to other diagnoses,
      production of purulent sputum (p = 0.014), hemoptysis (p = 0.006), pallor (p =
      0), skin lesions (p = 0.002) and a severe cough (p = 0.020) were significantly
      associated factors. On multivariate analysis, none of these factors were
      statistically significant. In fungal pneumonia, compared to other diagnoses,
      headache and papulonecrotic skin lesions were common findings, but no factor had
      a significant association. After four weeks, 59.3% of the patients were alive,
      13.6% died and 27.1% were lost to follow-up. Among the alive patients 88.6% had
      clinically improved. On multivariate analysis, no factor was shown to be a
      statistically significant predictor of death. The cumulative survival after 28
      days was highest among PCP patients, followed by bacterial pneumonia,
      tuberculosis and fungal pneumonia, but this difference was not statistically
      significant (p = 0.0453).

PMID- 16610650
TI  - Combating HIV/AIDS in Mainland China: an epidemiological review of prevention and
      control measures.
AB  - Two decades have already passed since the first HIV/AIDS case was described in
      1981. Cumulatively, over 20 million people have unfortunately lost their lives,
      and more than 40 million people are now living with HIV, and most of them are
      from developing countries. China, as the biggest developing country, has an
      impact on the epidemic of HIV/AIDS. From the first case of AIDS diagnosed in
      Mainland China in 1985, the epidemic has spread at an alarming rate. The feature
      of HIV/AIDS spread in Mainland China concerns its geographical characteristics
      that can be described as occurring in three phases. According to data from World
      Health Organization (WHO), it was estimated that about 840,000 people are living
      with HIV/AIDS in China, and 80,000 of them have already developed AIDS. WHO
      warned that, if there were no effective preventive measures adopted, that the
      number of HIV/AIDS infected cases would reach 10 million in China by 2010. In
      this study, we described the current situation of the epidemic of HIV/AIDS, as
      well as an historic review. The development of policy-making and the control
      measures are also highlighted. The experience from China described in this study
      would hopefully be for more public awareness of this crisis that is threatening
      all the citizenry of China.

PMID- 16610651
TI  - Domestic transmission of Rift Valley Fever virus in Diawara (Senegal) in 1998.
AB  - In 1998, circulation of the Rift Valley Fever (RVF) virus was revealed in Diawara
      by detection of IgM antibodies in sheep and isolation of the virus from
      mosquitoes caught outside a village. A seroprevalence study was carried out.
      Finger-prick blood samples, individual and collective details were obtained. One
      thousand five hundred twenty people (6 months - 83 years) were included. Overall
      prevalence in this group was approximately 5.2%. The prevalence in infants (6
      months - 2 years) was 8.5%. Age, gender, contact with a pond, presence of sheep,
      and abortion among sheep, and individual or collective travel history were not
      statistically associated with prevalence. Prevalence increased significantly when
      the distance to a small ravine, located in the middle of the village, decreased.
      The results suggest a low, recent, not endemic circulation of the virus. Culex
      quinquefasciatus was captured near the ravine. This mosquito, similar to Culex
      pipiens, can play a similar role in human-to-human transmission of the RVF virus.

PMID- 16610652
TI  - Seroprevalence of Burkholderia pseudomallei in East Timorese refugees:
      implications for healthcare in East Timor.
AB  - Melioidosis is a disease with protean clinical manifestations caused by the
      bacterium Burkholderia pseudomallei. It is endemic in countries surrounding the
      newly independent East Timor, but has yet to be isolated or demonstrated
      serologically in that country. One illness that can be clinically
      indistinguishable from melioidosis is pulmonary tuberculosis, a condition with a
      very high prevalence in East Timor. We used an indirect hemagglutination test
      (IHA) to measure antibodies to B. pseudomallei in 407 East Timorese evacuated to
      Darwin, Australia, in September 1999. Assuming a positive IHA titer as > or =
      1:40, the overall seroprevalence rate was 17.0%, in keeping with other
      seroprevalence studies from the region. The IHA titres ranged up to 1:320. After
      adjusting for age, females were 2.5 times more likely to be seropositive than
      males (p = 0.0001). There was an inverse relationship between seropositivity and
      age. This study shows that exposure to B. pseudomallei occurs in East Timor
      melioidosis is also likely to occur. Due to the lack of laboratory facilities at
      present, it may be some time before a laboratory-confirmed case proves that
      melioidosis occurs. In the meantime, clinicians in East Timor should include
      melioidosis in the differential diagnosis of the many conditions that it may
      mimic.

PMID- 16610653
TI  - Epidemiology of extended-spectrum beta-lactamase producing gram-negative bacilli
      at Siriraj Hospital, Thailand, 2003.
AB  - A cross-sectional study was conducted from August to September, 2003 to determine
      the prevalence and risk factors in acquiring extended-spectrum beta-lactamase
      (ESBL) producing gram-negative bacilli (GNB) in patients admitted to Siriraj
      Hospital and the outcomes of these infections. Of 346 isolates of gram-negative
      bacteria in 249 patients, 102 isolates from 87 patients were colonization only,
      but 244 isolates from 162 patients were infections. The common GNB were
      Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter
      baumannii and Enterobacter cloacae. The overall prevalence of ESBL producers was
      30.1%. K. pneumoniae had a very high prevalence of ESBL producers (56.9%). The
      urinary tract was the most common site for ESBL- producing GNB infections.
      Nosocomial infections, duration from admission to infection, peripheral line,
      urinary catheterization, nasogastric tube insertion and previous use of beta
      lactams, cephalosporins and fluoroquinolones were associated with acquiring ESBL
      producing GNB infections. ESBL-producing GNB were significantly more resistant to
      antimicrobial agents. More than 80% of ESBL-producing GNB were susceptible to
      carbapenems. Mortality in patients infected with ESBL-producing GNB (41.3%) was
      significantly higher than those infected with non- ESBL-producing GNB (19.8%).

PMID- 16610654
TI  - Epidemiology of antimicrobial resistance in Salmonella isolated from pork,
      chicken meat and humans in Thailand.
AB  - Forty samples each of pork and chicken meat were collected from local retail
      markets in Khon Kaen, northeast Thailand, for Salmonella isolation and
      identification during 2003. Fifty-four isolates of Salmonella obtained from
      diarrheal patients admitted at a hospital located in the same town were
      serotyped. All isolates were also tested for antimicrobial sensitivity against
      amoxicillin (Amx), chloramphenicol (Chl), norfloxacin (Nor), ciprofloxacin (Cip),
      gentamicin (Gm), sulfamethoxazole and Trimethoprim (Sxt), Tetracycline (Tet),
      Streptomycin (Str) and sulfamethoxazole (Sulfa). The results showed that 26 (65%)
      pork samples and 30 (75%) chicken meat samples were contaminated with Salmonella.
      The most prevalent serovar in pork was S. Rissen (61.5%), followed by S. Stanley
      and S. Lexington (11.5%). In chicken meat, the most prevalent serovar was S.
      Anatum (33.3%), followed by S. Rissen (16.7%). Among isolates from human
      patients, S. Rissen (20.4%) and S. Stanley (18.5%) were the most frequently
      identified serovars. All the isolates were resistant to Str and Sulfa. None were
      resistant to Nor and Cip. Resistance to Amx, Chl, Gm, Sxt, and Tet in pork was
      15.4, 15.4, 3.9, 15.4 and 88.5%, respectively. The resistance to those
      antimicrobial agents in chicken meat was 30.0, 26.7, 6.7, 20 and 100%,
      respectively, and in human patients was 27.8, 20.4, 5.6, 31.5 and 92.6%,
      respectively. Statistical analysis found no difference in the rate of resistance
      to Amx, Chl, Gm, and Sxt among the different sources of the Salmonella isolates
      (p > 0.05 for each antimicrobial agent). Our results indicate that antimicrobial
      resistant Salmonella strains were widely spread among pork and chicken meat, and
      in humans.

PMID- 16610655
TI  - Survey of leptospirosis of small mammals in Thailand.
AB  - During 1999-2000, kidney tissues of approximately 15% of 1310 rodents trapped
      from northeastern provinces of Thailand were tested for the presence of
      leptospires. Our direct immunofluorescent assay (DFA) for detection of
      leptospires showed 100% sensitivity and 94% specificity with the culture data.
      Both methods identified R. norvegicus as the highest source of infection. Among
      isolated Leptospira, 137 were serotyped by cross agglutinin absorption and/or a
      microscopic agglutination, and gave some variations and similarities at the
      serovar level to the DFA results. DFA data demonstrated over half of the positive
      animals were infected with several serovars of Leptospira interrogans. A
      subsequent DFA study in Bangkok in 2002 revealed leptospiral infection in 33% of
      42 rats and shrews. The most common infecting serovars were Autumnalis and
      Canicola identified in rural and urban animals, respectively. This finding
      suggests that wild small mammals may act as important sources of pathogenic
      leptospires and warrant active surveillance to understand the epidemiology of
      transmission and control of carrier animals.

PMID- 16610656
TI  - Bartonella species in rodents and shrews in the greater Jakarta area.
AB  - In February 2004, we captured 221 rodents and shrews in the Greater Jakarta area
      as part of a study to determine the prevalence of rodent-associated vector-borne
      infections. Microscopic examination of blood smears revealed 6% (13/218) to be
      positive for Bartonella spp. The corresponding DNA samples, either from blood
      blots or frozen spleen pieces and from fleas collected on these animals, were
      tested for evidence of Bartonella infection by PCR, targeting the portions: 378bp
      and 930bp of the citrate synthase gene (g/tA). The sequences from our sample
      clusters with a Peruvian entity, B. phoceensis, B. rattimassiliensis and B.
      elizabethae, the latter species has been associated with endocarditis and
      neuroretinitis in humans. As previous analyses have shown, there appears to be
      little geographic or host consistency with phylogenetic placement. The public
      health significance of these findings remains to be determined.

PMID- 16610657
TI  - Non-ulcerative soft tissue mycosis of long duration mimicking soft tissue sarcoma
      -a case report.
AB  - Soft tissue mycosis usually presents with a triad of tumefaction, suppuration and
      ulceration. We report an unusual case of soft tissue mycosis in a 42-year-old
      male teacher who presented with painless swelling over the anterolateral aspect
      of the right shin for 4 years duration.

PMID- 16610658
TI  - Comparison of two transcutaneous bilirubinometers--Minolta AirShields Jaundice
      Meter JM103 and Spectrx Bilicheck--in Thai neonates.
AB  - Transcutaneous bilirubin (TcB) has been reported to have a high correlation with
      serum bilirubin. The objectives of this study were: (1) to compare the accuracy
      of two transcutaneous bilirubinometer (Minolto AirShields Jaundice Meter, JM103
      (JM) and SpectRx, Bilicheck (BC) in estimating total serum bilirubin (TSB)
      levels; and (2) to assess the predictive ability of transcutaneous bilirubin in
      relation to specific selected TSB levels. A total of 154 measurements of TcB,
      using JM and BC, and TSB were recruited from 134 term and near-term infants.
      Postnatal ages ranged from 19 to 160 hours (x = 64.7, SD = 25.6). TSB levels
      ranged from 4.5 to 17.5 mg/dl (x = 10.4, SD = 2.5). The correlation coefficients
      between TcB (JM and BC) and TSB measurements were significant and similar (r 0.80
      and 0.82, respectively). The errors of distribution were, for TSB and TcB-JM, the
      mean difference of 0.7 mg/dl (SD 1.6 mg/dl and 95% confidence interval of the
      mean (CI) 0.4 and 1.0]; and, for TSB and TcB-BC, the mean difference of -0.6
      mg/dl (SD 1.5 mg/dl and 95% CI -0.4 and -0.8). TcB-JM had a tendency to
      underestimate TSB levels, and TcB-BC had a tendency to overestimate TSB levels.
      The sensitivity of BC was higher, but specificity was lower, than JM in
      corresponding to different TSB levels, except at a TSB level of 15 mg/dl when
      both instruments yielded 100% sensitivity. The accuracy of JM in predicting TSB
      was higher than BC at all TSB levels. Operating the JM was simple and
      uncomplicated. It would be suitable for clinical use when a number of personnel
      perform the measurement.

PMID- 16610659
TI  - Validation of osmotic fragility test and dichlorophenol indophenol precipitation
      test for screening of thalassemia and Hb E.
AB  - The strategy for screening of thalassemia and Hb E by a combination of osmotic
      fragility (OF) test and dichlorophenol indophenol precipitation (DCIP) test was
      validated with 436 unrelated Thai subjects. Hemoglobin (Hb) typing, Hb A2
      quantitation, PCR and DNA sequence analysis were used as confirmatory methods for
      diagnosis of thalassemia and hemoglobinopathy. The sensitivity and specificity of
      this strategy was 100% and 79.7%, respectively. The results assessed by two
      medical scientists were exactly the same with 93.3% accuracy in comparison with
      the confirmatory methods. A combination of OF and DCIP has been shown to be a
      reliable, rapid, simple and sensitive strategy for screening thalassemia and Hb E
      in the Thai population.

PMID- 16610660
TI  - Antimutagenic activity of Sesbania javanica Miq. flower DMSO extract and its
      major flavonoid glycoside.
AB  - The antimutagenic activity of Sesbania javanica Miq. or Sano, an edible vegetable
      flower DMSO extract against aflatoxin B1 (AFB1) benzo (a) pyrene [B(a)P], was
      evaluated by means of the Ames' test. The Sesbania javanica Miq. flower DMSO
      extract showed a strong inhibitory effect against AFB1 and B(a)P mutagens. A
      search to isolate the major flavonoid in Sesbania javanica Miq. flower extract
      found the flavonol glycoside, Quercetin 3-2(G)-rhamnosylrutinoside, which was
      confirmed by its physicochemical properties as a major constituent of the flower.
      Quercetin 3-2(G)-rhamnosylrutinoside (207 microg/plate) also showeda strong
      inhibitory effect against AFB1 and B(a)P with a more than 70% inhibition rate.

PMID- 16610661
TI  - A survey of the supply and bacteriologic quality of drinking water and sanitation
      in Jakarta, Indonesia.
AB  - We assessed the water supply, water quality and human waste disposal and their
      association with diarrheal illness in Jatinegara, East-Jakarta, where part of the
      area has been involved in the Kampung Improvement Program (KIP). Three hundred
      seventy-eight households, randomly selected in the study area, were visited and
      questioned about water source, sanitation and diarrheal illness during the
      previous 3 months. Microbiological quality of drinking water was assessed. The
      water sources were boreholes (243; 64%), the water mains (77; 20%), bottled water
      (45; 12%), and vendors or dug wells (243; 4%). Fecal coliforms were isolated in
      56% of the samples [median 23 (IQR 6-240) /100 ml in the contaminated samples].
      Only 2 (3%) of the water mains' samples contained >100 fecal coliforms/100 ml,
      compared to 57 (24%) groundwater samples. Most residents used private toilets
      with drainage into on-site septic tanks, yet in over one quarter of households
      human excreta was disposed of into rivers or gutters. KIP areas lagged behind in
      environmental hygiene. Diarrheal episodes, reported in one third of the
      households, were significantly associated with water contaminated with >100 fecal
      coliforms/100 ml [OR 2.4 (95% CI: 1.4-4.2)], but no association with water source
      or environmental contamination was found. Significantly, all individuals reported
      boiling water before consumption.

PMID- 16610662
TI  - Knowledge, attitudes and practices (KAP) regarding the management of diarrhea by
      pharmacists and licensed drug sellers in eastern Nepal.
AB  - Diarrhea constitutes a major cause of morbidity and mortality in developing
      countries. Inappropriate drug prescribing is common in diarrhea, resulting in an
      increase in cost and adverse drug reactions. In Nepal, drug sellers often act as
      the first contact persons for the underprivileged. No information has been
      available regarding their knowledge, attitudes and practices (KAP) regarding
      diarrhea management. Using a structured questionnaire, between the 1st of January
      and the 31st of December 2003, 109 drug sellers in eastern Nepal were interviewed
      about their educational status, patient/attendant presentation at the outlet and
      their advice to patients/attendants. Only 2.7% of drug sellers were qualified in
      health education. Eighty percent of the patients/attendants sought advice from
      the drug sellers, only 20% presented to the outlet with prescriptions. The data
      reveals that about half of them were taking note of the nature of the diarrhea.
      Although 62 (56.8%) of them were aware of dehydration, only 2 (1.8%) of them knew
      all three signs of dehydration (dry tongue, non-elastic skin and sunken eyes).
      Sixty-six (60.5%) of them knew about oral rehydration solution (ORS), its
      principle and the required period of administration. About 50 to 60% of them were
      aware of the implications resulting from dehydration from uncontrolled diarrhea
      and of the importance of ORS in its management. Only 20% of the drug sellers
      advised ORS alone, otherwise it was dispensed along with drugs, such as
      antimotility agents (AMA) or metronidazole. As a result of the above findings, it
      is important to educate the drug sellers by conferring knowledge about the
      ethical aspects of drugs in the management of diarrhea.

PMID- 16610663
TI  - Causal relationship between health promoting behavior and quality of life in
      cervical cancer patients undergoing radiotherapy.
AB  - The purpose of this cross-sectional study was to examine the causal relationships
      among age, education, family income, and stage of carcinoma, perceived benefits,
      perceived barriers, perceived self-efficacy, health promoting behavior and
      quality of life in patients with cervical cancer. Pender's Health Promotion Model
      (1996) provided a guide for the conceptual framework of this study. Purposive
      sampling was employed to recruit 488 cervical cancer patients who were undergoing
      radiotherapy at seven public hospitals in five areas of Thailand. The instruments
      used in this study included a Personal Data Form, Cognitive perception Form,
      Health promoting behavior scale, the social support questionnaire and The
      Functional Assessment of Cancer Therapy General (FACT-G) form. The proposed model
      was tested and modified by the LISREL Program. The modified model adequately
      fitted with the data. The results demonstrate that health promoting behavior had
      a significant direct positive effect on quality of life (beta = 0.71, p < 0.01).
      Cognitive perceptual factors had a significant direct effect on health promoting
      behaviors (P = 0.69, p < 0.01). Social support had a significant direct effect on
      the cognitive perceptual factors (P = 0.64, p < 0.01), health promoting behavior
      (beta = 0.70, p < 0.01), and the quality of life (beta = 0.48, p < 0.01). Age and
      education did not have a significant total effect on the quality of life. Family
      income had a significant direct effect on cognitive perceptual factors (beta =
      0.10, p < 0.05). The stage of cancer had a significant direct negative effect on
      cognitive perceptual factors (beta = -0.11, p < 0.05) and the quality of life
      (beta = -0.12, p < 0.01). The direct effect of the predictors on the quality of
      life indicated that cervical cancer patients with higher practice of health
      promoting behavior tended to have a higher quality of life. The findings indicate
      that Pender's Health Promotion Model is a useful guide for explaining and
      predicting the health promoting behavior and the quality of life of Thai cervical
      cancer patients who were undergoing radiotherapy. The significance of cognitive
      perceptual factors and social support confirm health promoting behavior as a goal
      directed towards the level of well being. This has implications for health care
      systems in planning interventions to promote health promoting behavior in a
      health promotion setting in cervical cancer patients for a better quality of life
      and healthy. A longitudinal study and experimental study are recommended for
      further study.

PMID- 16610664
TI  - Lead in saliva and its relationship to blood in the residents of Klity Village in
      Thailand.
AB  - Lead concentrations in whole blood and saliva were examined in 16 females and 13
      males living in Klity village, a highly contaminated area from lead mining,
      Thailand. The geometric mean for the lead content in the blood was 24.03
      microg/dl (range 11.80-46.60 microg/dl) while the lead content in the saliva was
      5.69 microg/dl (range 1.82-25.28 microg/dl). No significant differences were
      found between the concentrations of lead in blood and saliva in relation to the
      age of the subject. Males were found to have higher blood lead levels than
      females. The coefficient of correlation gamma between salivary and blood lead
      levels was -0.025. Our data suggests that saliva is not suitable material for
      biological monitoring with respect to lead exposure.

PMID- 16610665
TI  - A cross-sectional study of smoking risk factors in junior high school students in
      Henan, China.
AB  - This study was conducted to determine the predictors of tobacco use among junior
      high school students in Henan. Two thousand seven hundred sixty-three students
      (from grades 7 to 9) were studied. Demographic, smoking-related, and other
      predictor variables was investigated. Overall, 6.6% of students were current
      smokers; 8.7% students reported having tried cigarettes before; and 42.1% of
      current smokers and 34.2% of triers experimented with smoking during ages 10-12.
      Of the factors associated with student tobacco use, mother and peer smoking were
      the strongest independent predictors. The school's negative attitude towards
      smoking was an important protective factor for preventing student smoking
      behavior. These findings revealed that effective smoking prevention interventions
      needed to be comprehensive.

PMID- 16610666
TI  - [Monitoring and official control of pesticide residues in foodstuffs in Poland in
      2004].
AB  - Poland, as a Member State of the European Union, is obliged to establish
      efficient system of food control allowing assessment of health quality of food
      products for general population as well as for high risk groups, like infants and
      toddlers. In case of pesticide residues this task is realized by carrying out
      programs of monitoring and official control of foodstuffs in order to check
      compliance with Maximum Residue Levels set up by Polish Regulation of Minister of
      Health on maximum residue levels of pesticides in or on food. The Chief Sanitary
      Inspectorate is an authority responsible for above mentioned activities with
      essential participation of Department of Environmental Toxicology of National
      Institute of Hygiene. The analysis of food samples indicated in yearly developed
      plans of sampling, is carried out in 16 integrated local laboratories of National
      Sanitary Inspection. In 2004, 868 samples have been analyzed in system of
      monitoring and official control of foodstuffs in Poland. The samples were taken
      in retail and wholesale. Among analyzed samples 67% were fresh or frozen fruit
      and vegetables, and 14% were baby food. The samples have been analyzed or
      presence of over 50 pesticides. In the year 2004 maximum residue levels have been
      exceeded in 14 samples (2%) of fruit, vegetables and cereals. All samples were of
      Polish origin, except two samples from Spain. In samples with violated MRLs the
      following pesticides have been found: Benomyl group, Maneb group, Endosulfan,
      Mecarbam, Hexachlorobenzene, and Methyl bromide. Additionally, 49 follow-up
      enforcement samples has been analyzed. In none of them MRLs violation have been
      found.

PMID- 16610667
TI  - [Polycyclic aromatic hydrocarbons (PAHs) in herbs and fruit teas].
AB  - Polycyclic aromatic hydrocarbons (PAHs) of which benzo[a]pyrene is the most
      commonly studied and measured, are fused - ring aromatic compounds formed in both
      natural and man made processes and are found widely distributed throughout the
      human environment. PAHs occur as contaminants in different food categories and
      beverages including water, vegetables, fruit, cereals, oils and fats, barbecued
      and smoked meat. The sources of PAHs in food are predominantly from environmental
      pollution and food processing. PAHs emissions from automobile traffic and
      industry activities were show to influence the PAHs levels in vegetables and
      fruits. The present study was carried out to determine levels of 16 basic PAHs in
      herbs and fruit teas. The method was based on the hexane extraction and cleaned
      up by florisil cartridge. The extracts were analysed by GC-MS. The levels of
      total PAHs varied from 48,27 microg/kg (hibiscus tea) to 1703 microg/kg (green
      tea). The highest level of BaP was found in lime tea (74,2 microg/kg).

PMID- 16610668
TI  - [Determination of ochratoxin a in spices].
AB  - The method of determination of ochratoxin A in some spices: coriander, cloves,
      ginger, paprika, black pepper was described. Depending on kind of matrix,
      extraction with metanol/water (80/20) or with solution of 1% NaHCO3 and several
      variants of clean-up on IAC columns were investigated. The most useful extraction
      solvent appeared water solution of 1% NaHCO3. In case of cloves only, none of the
      methods of extraction and clean-up variants was appropriate. The mean recovery of
      the method, dependent on kind of sample, was 61-82% and RSD% 1.4 and 7.8. The
      estimated LOD and LOQ were 0.02 and 0.06 microg/kg, respectively. In samples of
      spice used for method preparation, ochratoxin A was detected on the level 3.4-4.6
      microg/kg.

PMID- 16610669
TI  - [Study on the quantitative and qualitative composition of fungi in dried
      medicinal plants].
AB  - The quantitative and qualitative composition of fungi was determined in selected
      dried medicinal plants purchased in one of the herbal shops in Szczecin, Poland.
      The samples examined were as follows: chamomile (Flos Chamomillae), peppermint
      (Folium Menthae piperitae), lemon balm (Folium Melissae), St. John's wort (Herba
      Hyperici), and two herbal mixtures. The fungal composition depended on the
      specified sample. Xerophilic fungi, i.e. Eurotium amstelodami, E. herbariorum, E.
      rubrum and Wallemia sebi were isolated from dried medicinal plants. E.
      amstelodami was the predominating species. The prevailing thermophilic and
      thermotolerant species were Rhizopus microsporus var. rhizopodiformis and
      Aspergillus fumigatus. Pink and white yeasts were also numerous in some samples.
      Except for Aspergillus niger, mesophilic and toxigenous species were found to
      occur infrequently in the samples. However, Aspergillus versicolor was found to
      occur abundantly in lemon balm.

PMID- 16610670
TI  - Effects of nitric oxide syntase inhibitor on exercise-mediated pro- and anti
      oxidative balance in rat blood plasma.
AB  - Studies showed that nitric oxide synthase (NOS) inhibitor Nomega-nitro-L-arginine
      methyl ester (L-NAME), enhanced anti-oxidative shifts in the blood plasma of rats
      subjected to exhaustive running exercise. A type of running training (continuous
      endurance and intermittent) before the exhaustive exercise was found to
      differentiate L-NAME-induced effects in rats.

PMID- 16610671
TI  - Lipolytic activity and radial daily growth rate changes during incubation of
      thermomyces lanuginosus on natural and synthetic fatty substrates.
AB  - The aim of the study was to compare lipolytic activity and radial growth rate
      changes during the incubation of Thermomyces lanuginosus strains on natural
      (sunflower oil, soybean oil, rapeseed oil, and corn oil) and synthetic
      (tributyrin, Tween 20, Tween 40, Tween 60, Tween 80, and Tween 81) fatty
      substrata. The general lipolytic activity index decreased on natural substrata
      and increased on synthetic substrata during a five-day incubation period. The
      general daily growth rate changes were found to be similar on both natural and
      synthetic fatty substrates.

PMID- 16610672
TI  - [Copper and zinc in food products for infants and children].
AB  - Ready to use infant food, namely 7 types of fruit and vegetable juices, 7 types
      of vegetable-meat soups and 8 types of dinner vegetable-meat meals, was
      investigated by the flame AAS towards the copper and the zinc content. The
      average levels of the copper and the zinc were respectively--for the juices: 0.31
      mg/kg and 0.51 mg/kg, for the soups: 0.38 mg/kg and 2.60 mg/kg, for the dinner
      meals: 0.42 mg/kg and 2.98 mg/kg. Consumption of a single unit pack of all the 3
      types of food products will cover 29% of recommended daily copper intake and 22%
      of zinc.

PMID- 16610673
TI  - [Survival and habitual nutrient intake among elderly men].
AB  - The aim of this paper was to determinate whether the intake of energy and
      nutrients was associated with all-cause mortality in the elderly men of the
      Warsaw region. Data on the intake of energy and nutrients were collected using a
      3-day record method, in spring 1999. The mortality follow-up period lasted until
      December 31, 2003. During this period 43 men (29.5 % subjects) died. The all
      cause mortality was higher among subgroup of elderly men with lower intake of
      carbohydrates, dietary fiber, vitamin B1, vitamin B6, vitamin PP, potassium,
      phosphorus, magnesium, zinc, copper and among subgroup of men with lower intake
      of total fat, saturated and monounsaturated fatty acids.

PMID- 16610674
TI  - [Some nutritional habits of a group of overweight and obese women].
AB  - The aim of the project was to research the nutritional habits of overweight and
      obese women. The group under investigation consisted of 100 randomly chosen women
      from the region of Malopolska. Their diet turned out to be inconsistent with
      proper nutrition. The majority of the women (80%) confessed not to reducing the
      cholesterol intake. About 50% of the researched did not pay attention to the food
      products containing the salt and sugar. Fast-food products and fat meat were
      commonly. The women were aware that their diet was not proper from the
      nutritional point of view.

PMID- 16610675
TI  - [Application of mathematical models for determination of volatile organic
      compounds emission from flooring adhesives].
AB  - An environmental chamber with controlled temperature, relative humidity, and air
      exchange was used to evaluate emissions of volatile organic compounds (VOC) from
      three flooring solvent-based adhesives. Gas chromatograph equipped with flame
      ionization detector was employed to measure VOC emission. The temporal change in
      concentration of VOC emitted from each adhesive was observed and double
      exponential model was compared with a first-order emission decay model in their
      ability to describe measured emission factors of adhesives. It was demonstrated
      that the double exponential model better describes emission characteristic for
      experimental data than first-order model does.

PMID- 16610676
TI  - Tissue microarrays meet cytopathology.

PMID- 16610677
TI  - Tissue microarrays for testing molecular biomarkers of cervical intraepithelial
      neoplasia: feasibility study.
AB  - OBJECTIVE: To test the possibility of creating tissue microarrays of pre
      malignant lesions of the cervix. STUDY DESIGN Paraffin-embedded blocks of 240
      cervical tissue specimens were sampled. Lesions from benign squamous and
      glandular epithelium through various grades of cervical intraepithelial neoplasia
      (CIN) to frank carcinoma of squamous and glandular origin were cored with a 0.6
      mm needle and arrayed in 4 tissue blocks. Sections of these blocks were stained
      with hematoxylineosin (H-E) and evaluated as to adequacy of tissue cores,
      representativity of the material and correspondence to the original diagnosis.
      Immunohistochemical staining with p16 and a novel marker C4.8(4/2/#1) was
      performed. RESULTS: In > 80% of cases sufficient material from the lesion could
      be obtained. No or inadequate material was seen in 6% of cases. The core sample
      did not correspond to the original diagnosis in 12% of cases. The reason was
      mainly a discrepancy in the grade of the CIN. Discrepancies in diagnoses occurred
      in only premalignant lesions. Immunohistochemical staining could reliably be
      performed and evaluated on all tissue cores. CONCLUSION: Tissue microarrays of
      cervical intraepithelial lesions are technically feasible and can be created
      reliably. The key to success is a careful and repeated comparison of the tissue
      block with the corresponding H-E section. Tissue microarrays of preinvasive
      cervical lesions may allow high throughput analysis of emerging molecular
      biomarkers in cervical carcinogenesis.

PMID- 16610678
TI  - Diagnostic efficacy of immunocytochemistry on fine needle aspiration biopsies
      processed by thin-layer cytology.
AB  - OBJECTIVE: To evaluate the efficacy of immunocytochemistry (ICC) performed on
      smears processed by thin-layer cytology (TLC). STUDY DESIGN: During the period
      January 2001-September 2003, 3,573 consecutive fine needle aspiration biopsies
      were processed with both conventional smears (CSs) and TLC diagnosed by a single
      pathologist; 113 required immunocytochemical study. CSs were fixed in ethanol
      whereas TLC slides were processed with the ThinPrep 2000 method (Cytyc Co.,
      Marlborough, Massachusetts, U.S.A); both were stained with Papanicolaou stain.
      ICC staining was carried out on only TLC slides. RESULTS: The 113 cytologic cases
      were grouped as follows: 32 thyroid nodules with 16 histologic controls (HCs), 24
      lymph nodes (regardless of location) with 15 HCs, 18 liver and pancreatic lesions
      (3 HCs), 11 lung nodules (6 HCs), 5 kidney and adrenal gland lesions (1 HC), 6
      abdominal (2 HCs) and 4 mediastinal masses (1 HC), 6 salivary gland tumors (3
      HCs), 4 bone masses (2 HCs) and 3 subcutaneous lesions (1 HC). ICC contributed to
      the diagnosis in 104 cases (92%), whereas it was inconclusive in 9. The cytologic
      diagnoses were histologically confirmed in 46 of 50 cases (92%). CONCLUSION: ICC
      can be successfully applied on TLC slides with better results than on CSs, and
      its yield can be useful in making the correct diagnosis on fine needle aspiration
      biopsy.

PMID- 16610679
TI  - Acetic acid recovery of gynecologic liquid-based samples of apparent low squamous
      cellularity.
AB  - OBJECTIVE: To characterize cervicovaginal cytology samples with < 5,000 squamous
      cells on the initial ThinPrep slide (Cytyc Corp., Boxborough, Massachusetts,
      U.S.A) and to attempt sample recovery using acetic acid. STUDY DESIGN:
      Cervicovaginal cytology samples with <5,000 squamous cells on the original
      ThinPrep slide and residuum were reprocessed by adding 3 mL of 3:1 CytoLyt
      (Cytyc)/glacial acetic acid with production of a second slide. Both slides were
      reviewed for squamous cell quantitation and the presence of background material
      and abnormal cells. RESULTS: From a total of 1,833 cases, 147 (8.0%) were
      identified for reprocessing; 71 (48.3%) were grossly bloody and 58 (39.4%)
      grossly cloudy. Reprocessing resulted in a second slide with > 5,000 squamous
      cells in 116 (78.9%) cases and was most effective on cloudy samples (89.7%
      recovery) and bloody samples (71.8% recovery). Abnormal cells were identified in
      13 (8.9%) reprocessed samples. In all but 2 cases the abnormal cells were present
      on the initial slide and demonstrated the same degree of abnormality as the
      reprocessed slide but were fewer in number. CONCLUSION: Acetic acid recovery
      increases squamous cell recovery when initially inadequate, reducing the number
      of unsatisfactory cases and in rare cases identifying a cytologically significant
      lesion not apparent on the original slide.

PMID- 16610680
TI  - A method of assessing the adequacy of trucut biopsy specimens obtained with a 19
      gauge trucut core biopsy needle.
AB  - OBJECTIVE: To develop a simple and accurate method of evaluating trucut biopsy
      (TCB) specimen. STUDY DESIGN: We performed 40 ex vivo TCBs of surgical specimens
      under direct visual guidance with the Quick-Core needle (Wilson-Cook, Winston
      Salem, North Carolina, U.S.A). Touch preparations were made using 4 methods.
      Slides were stained with a modified Wright-Giemsa stain, and biopsies were
      processed for histology. Slides were blindly classified as malignant, suspicious,
      atypical, benign or inadequate. The ease of the 4 touch preparation methods was
      compared. RESULTS: There were 20 TCBs of benign tissue and 20 of malignant
      tissue. Cytologic interpretation could be made in 34 of 40 cases and was correct
      in 25 of 34 cases. Touching the biopsy to a glass slide was significantly easier
      than the 3 other methods tested. CONCLUSION: Touch preparations can be made
      easily with TCB samples and can provide information about specimen adequacy and
      diagnosis.

PMID- 16610681
TI  - Testicular fine needle aspiration cytology in male infertility.
AB  - OBJECTIVE: To compare the accuracy of testicular fine needle aspiration and
      biopsy for diagnostic and therapeutic purposes. STUDY DESIGN: A comparison of
      testicular fine needle aspiration and biopsy was performed on 34 infertile men
      over a 2-year period. RESULTS: Concordance of the 2 tests was evident in 88% of
      cases. In discordant cases fine needle aspiration yielded more than biopsy,
      considering the existence of secondary spermatocytes and spermatids. Charcot
      Bottcher crystalloids were frequently seen in the cytoplasm of Sertoli cells in
      normal and abnormal spermatogenesis. CONCLUSION: Testicular fine needle
      aspiration is a simple and cost-effective method of evaluating testicular
      pathology in male factor infertility. It may yield more diagnostic and
      therapeutic material than does biopsy.

PMID- 16610682
TI  - Robinson cytologic grading in invasive ductal carcinoma of the breast:
      correlation with E-cadherin and alpha-, beta- and gamma-catenin expression and
      regional lymph node metastasis.
AB  - OBJECTIVE: To correlate the cytologic grade of breast carcinoma with the
      expression of E-cadherin/catenin system molecules and the presence of metastasis
      in regional lymph nodes. STUDY DESIGN: Aspirate smears were examined together
      with histologic sections from the corresponding neoplasms taken from 100 patients
      with invasive ductal carcinoma. In 50 cases, > or = 1 metastatic nodes were
      identified. Cytologic grading of the smears was performed using the Robinson
      method. Immunohistochemical expression of E-cadherin and of alpha-, beta- and
      gamma-catenin was studied. RESULTS: A statistically significant relationship was
      observed between E-cadherin/catenin expression and cytologic grade (p < 0.0005).
      This association was particularly relevant to the cell dissociation parameter (p
      < 0.0005). CONCLUSION: The cytological grade established in preoperative studies
      may provide relevant information on the aggressiveness of invasive ductal
      carcinoma and its tendency to produce regional metastasis. This finding could be
      particularly useful in cases of breast carcinoma in which neoadjuvant therapy is
      the method of choice.

PMID- 16610683
TI  - Endometrial scraping cytology in women with extragenital malignancies.
AB  - OBJECTIVE: To clarify the usefulness of endometrial scraping smears in women with
      extragenital malignancies. STUDY DESIGN: A total of 4,335 endometrial scraping
      smears were obtained during the 5-year period 1995-1999 at the National Kyushu
      Cancer Center and were retrospectively analyzed regarding extragenital
      malignancies. RESULTS: There were 88 cases of extragenital malignancies.
      Extragenital malignant cells were detected in endometrial smears in 13 cases. The
      cases consisted of 4 gastric cancers, 4 breast cancers, 2 lung cancers, 1 rectal
      cancer, 1 gastrointestinal stromal tumor of the small intestine and 1 case of
      adenocarcinoma of unknown origin. The patients' average age was 52.5 years. The
      symptoms and signs included abnormal vaginal bleeding, abdominal and lumbar pain,
      lower limb edema, abdominal mass and neck lymph node swelling. Both ascites and
      peritoneal dissemination were found in 8 cases. Ten of the 13 cases were
      diagnosed as of extrauterine origin based on the characteristic cancer cell
      appearance, the absence of cellular detritus among the poorly differentiated
      adenocarcinomas and, above all, the morphologic difference between normal
      endometrial cells and cancer cells. CONCLUSION: Endometrial scraping smears are
      useful for detecting extragenital malignant cells that enter the uterine cavity.

PMID- 16610684
TI  - Toward implementation of a regional quality assurance program in cytopathology:
      the Hong Kong experience.
AB  - OBJECTIVE: To develop a local quality assurance program in cytopathology based on
      circulation of patient specimens on glass slides, with limited resources. STUDY
      DESIGN: A working group was set up for design and running of the program.
      Participation is on a laboratory basis. The scope and frequency of testing are
      defined. Well-documented cases (including gynecologic, nongynecologic and fine
      needle aspiration cytology) with commonly encountered diagnoses are collected.
      Consensus concerning the diagnosis, interpretive menu and scoring system is
      sought before the actual slide circulations using express mail. After returning
      their answers to the program organizer, the participating laboratories receive
      immediate feedback on their scores, with reference answers, explanatory notes,
      "whole-mount" images of glass slides and cumulative responses of peer
      laboratories for on-site checking. At the end of each year, an electronic file
      containing representative photomicrographs of all cases examined is provided to
      individual laboratories for their permanent records and training purposes.
      RESULTS: The program was launched in mid-2003. There were 24 and 27 participating
      laboratories from Hong Kong (and Macau) in 2003 and 2004, respectively. To date,
      >150 well-documented cytology cases are available in the slide pool and ready for
      circulation. As the revenue is mainly to cover the expenses of express mail, the
      program can be carried out at a relatively low cost. CONCLUSION: In order to have
      any cytology quality assurance program accepted by local laboratories, it has to
      be fair and practical. Strict confidentiality needs to be observed throughout the
      process. This program emphasizes both performance assessment and educational
      value. Adequate representation from experienced local cytology workers, detailed
      documentation support from authorities and assistance from dedicated staff are
      essential to the success of any external proficiency testing scheme. Regular
      review and evaluation are also necessary for continuous improvement. The Hong
      Kong experience can serve as an example of running a glass slide-based cytology
      quality assurance program in a small region with limited resources.

PMID- 16610685
TI  - Endocervical and metaplastic cells: comparison of endocervical and metaplastic
      cell number in Papanicolaou smears with and without squamous intraepithelial
      lesion.
AB  - OBJECTIVE: To compare, with a retrospective study, endocervical and metaplastic
      cell number to identify the cytology of squamous intraepithelial lesion (SIL) of
      the cervix. STUDY DESIGN: Cytology files from March 2000 to March 2003 were
      reevaluated, and those with SIL were identified. RESULTS: In 8,743 cervicovaginal
      smears were found 70 (0.8%) SIL smears (39 low grade, 31 high grade) and 140
      randomly selected smears without squamous or glandular abnormalities that were
      not atrophic or unsatisfactory. Endocervical and metaplastic cells counted in
      these smears and then classified into 5 groups were compared with each other.
      CONCLUSION: Women with smears containing endocervical cells are not at greater
      risk for SIL than those with smears lacking these cells. Women with smears
      containing metaplastic cells are more likely to have SIL than those without
      metaplastic cells. In addition, high grade lesions are more likely in smears
      containing more metaplastic cells.

PMID- 16610686
TI  - Sensitivity of the Pap test in detecting high grade lesions: what should be the
      acceptable cytologic threshold for colposcopic referral?
AB  - OBJECTIVE: To devise an optimal cytology threshold for colposcopy referral in
      resource-limited settings. STUDY DESIGN: Four hundred seventy-two symptomatic
      women 20-60 years old were screened by both cytology and colposcopy. Onsite
      biopsy was taken if lesions grade 1 or above were detected on colposcopy. Women
      found to have cervical intraepithelial neoplasia (CIN) 2 and above lesions on
      histopathology were stratified according to their cytologic diagnosis (atypical
      squamous cells of undetermined significance [ASCUS]+ threshold, low grade
      squamous intraepithelial lesion [LSIL]+ threshold, and high grade squamous
      intraepithelial lesion [HSIL]+ threshold). The comparative sensitivity,
      specificity and predictive values in each group were calculated, taking biopsy as
      the gold standard. RESULTS: The sensitivity of LSIL + cytology to detect CIN 2+
      lesions was 91.5% (referral load, 30.7%). While the sensitivity of ASCUS+
      cytology threshold was almost the same (92.3%), the referral load was much higher
      (42.2%). With HSIL+ cytology threshold, though the referral load was reduced
      substantially (21.9%), the sensitivity also decreased, to 81.5%. CONCLUSION: The
      results indicate that in order to achieve high sensitivity, the LSIL cytology
      threshold appears to be optimum for colposcopic referrals.

PMID- 16610687
TI  - Investigation of 208 consecutive cases of cervical cone biopsies with regard to
      indication, negative samples and quality control.
AB  - OBJECTIVE: To analyze factors in preoperative management and cytologic screening
      leading to a conization specimen free of neoplasia. STUDY DESIGN: From January
      2001 through December 2003, cervical conization was performed on 208 consecutive
      cases at the Gynecologic Department, Krankenhaus Lainz, Vienna. Indications for
      cone biopsy were based on suspicious internal and/or external conventional
      cytologic screening results followed by punch biopsies in selected cases.
      RESULTS: Benign cervical lesions were diagnosed in 22 women (10.6%). Histologic
      results in negative cone biopsies were cervicitis (n = 12), infection with HPV
      without cervical intraepithelial neoplasia (n = 1), tubal metaplasia (n = 4) and
      combined diagnoses indicating no neoplasia (n = 5). Regarding cytologic screening
      results prior to conization, long-lasting infections with HPV can cause repeated
      findings of cells of unknown origin or reversible mild to moderate dysplasia
      eventually leading to conization specimens free of neoplasia. Furthermore, tubal
      metaplasia is a frequent pitfall in misinterpretation of cytologic smears.
      CONCLUSION: Reevaluation of cytologic screening results after the final
      histologic diagnosis becomes available following cone biopsy is a key issue in
      continuous quality assurance for the diagnostic procedure. In this article we
      also present a method of stratifying screening results according to the
      correctness of the results. Along with other established measures of diagnostic
      performance, this may support benchmarking and interpretation of the overall
      cytologic screening quality.

PMID- 16610688
TI  - Scientific issues related to the cytology proficiency testing regulations.
AB  - The member organizations of the CETC feel strongly that there are significant
      flaws associated with the proposed proficiency test and its implementation. The
      most immediate modifications include lengthening the required testing interval,
      utilizing stringently validated and continuously monitored slides, changing the
      grading scheme and changing the focus of the test from individuals to laboratory
      level testing, as described above. Integration of new computer-assisted and
      location-guided screening technologies into the testing protocol is necessary for
      the testing program to be compliant with the current CLIA law. The regulation
      also needs to be flexible enough to accommodate new technologies that are
      implemented in laboratory practice, education and administration of the test. The
      changes recommended in this document address the most immediate technical and
      scientific concerns with the current implementation of PT for gynecologic
      cytology. The CETC will be submitting a subsequent document, following full
      review of the current regulations, with recommendations for changes,
      justifications and impact.

PMID- 16610689
TI  - Uremia associated with erythrophagocytosis by small intestine epithelial cells: a
      case report.
AB  - BACKGROUND: Anemia is a frequent finding in patients with uremia due to chronic
      renal failure. Two factors contribute to the decrease in the red blood cell count
      and worsen the patient's general status: depression of erythropoiesis and
      shortening of the red blood cell lifespan. CASE: A novel response mechanism to
      erythrocyte loss took place in a uremic patient with gastrointestinal hemorrhage.
      In an autopsy case of an 80-year-old woman dying of uremia, analysis of an
      intestinal fluid smear revealed small intestine epithelial cells engulfing
      complete erythrocytes. CONCLUSION: This cytologic finding could account for a
      potential response mechanism to counteract the massive erythrocyte loss that
      occurs in hemorrhagic anemia with a uremic background.

PMID- 16610690
TI  - Metastatic anaplastic carcinoma of the thyroid mimicking squamous cell carcinoma:
      report of a case of a challenging cytologic diagnosis.
AB  - BACKGROUND: The probability of anaplastic transformation in a differentiated
      thyroid carcinoma (DTC) is <2%. Admixture of DTC and undifferentiated carcinoma
      can occasionally be found in thyroidectomy specimens, or the undifferentiated
      tumor may develop in metastatic foci months or years after removal of the primary
      tumor. CASE: Anaplastic transformation of a metastatic DTC was diagnosed at
      autopsy in a 71-year-old female. At the time of her total thyroidectomy for
      follicular carcinoma, she already had several lung nodules, which diminished in
      size upon 131I treatment. Five years later the patient developed a new, pleura
      based lung mass. The mass extended along the paraspinal soft tissue and involved
      the kidney. Fine needle aspiration biopsy of the paraspinal mass resulted in a
      diagnosis of metastatic squamous cell carcinoma. Two months later the patient
      died. Histologic evaluation of the lung nodules and pleura-based mass revealed
      areas of follicular carcinoma intermixed with a various patterns of
      undifferentiated carcinoma. The paraspinal and kidney mass consisted entirely of
      anaplastic tumor, including areas of squamoid differentiation. CONCLUSION: In
      patients with a history of DTC who develop a rapidly growing mass elsewhere, a
      possibility of metastatic DTC with anaplastic transformation must be considered.

PMID- 16610691
TI  - Cytologic diagnosis of small cell anaplastic hepatoblastoma: a case report.
AB  - BACKGROUND: Small cell anaplastic hepatoblastoma (HB) is the least common subtype
      of HB. There are few articles in the literature describing the cytologic
      characteristics of this rare subtype. CASE: A 5-year-old girl present with a
      progressively enlarging abdominal mass. Ultrasound examination revealed the mass
      to be arising within the right lobe of the liver. Fine needle aspiration (FNA) of
      the mass revealed primitive cells with a high nuclear/cytoplasmic ratio and
      hyperchromatic, ovoid nuclei in poorly cohesive clusters as well as dispersed
      singly. These cells closely resembled those of small round cell tumors of
      childhood. CONCLUSION: The cytologic differential diagnosis of undifferentiated
      HB must include small round cell tumors of childhood. With knowledge of the
      typical cytomorphologic appearance of HB in association with clinical and
      radiologic information, one can offer a reliable preoperative diagnosis on FNA.

PMID- 16610692
TI  - Low grade fibromyxoid sarcoma: report of a case with fine needle aspiration
      cytology and histologic correlation.
AB  - BACKGROUND: Low grade fibromyxoid sarcoma has been fully described
      histologically; however, the fine needle aspiration (FNA) cytologic findings are
      scantily defined, and the distinction from other benign and malignant soft tissue
      tumors can be difficult. CASE: We examined FNA cytologic material from a slowly
      growing, large chest wall mass in a 28-year-old woman. The surgical specimen was
      processed for routine histology and immunohistochemical studies. The cytologic
      smears were adequately cellular, showing spindly cells with uniform, elongated
      nuclei; small, inconspicuous nucleoli; and scanty, wispy cytoplasm associated
      with myxoid material. No significant nuclear pleomorphism or mitoses were noted.
      The excised tumor was well circumscribed, focally infiltrating the surrounding
      muscles. The cut surface was variable, featuring fibrous, solid, fleshy and
      myxoid areas. Microscopically, the solid, fibrous areas displayed increased
      cellularity with storiform, intersecting and parallel patterns. In the myxoid
      areas the cells grew in a haphazard fashion and appeared floating in abundant
      mucoid matrix associated with a capillary vascular network similar to the chicken
      wire pattern seen in cases of myxoid liposarcoma. The tumor cells were spindly,
      with fusiform, uniform nuclei. Focal, moderate nuclear pleomorphism was noted.
      The mitotic index was low. The tumor cells were positive for vimentin, alpha-1
      antitrypsin and lysozyme and negative for S-100, actin, desmin and CD34.
      CONCLUSION: Although low grade fibromyxoid sarcoma is a rare neoplasm, it should
      be recognized and distinguished from other soft tissue tumors because of its low
      malignant potential. The definitive FNA cytologic diagnosis can be challenging
      but is possible if the tumor is adequately sampled, with multiple passes from
      different areas. Clinical and radiologic correlations are of great help. All
      spindle cell tumors with myxoid changes, such as myxoid liposarcoma,
      myxofibrosarcoma, cellular myxoma, myxoid leiomyosarcoma and peripheral nerve
      sheath tumors, should be considered in the differential diagnosis. In contrast to
      the cytologic features, the histologic findings are characteristic and well
      established.

PMID- 16610693
TI  - Esophageal rhabdomyosarcoma: report of a case diagnosed by imprint cytology.
AB  - BACKGROUND: Primary esophageal rhabdomyosarcoma (PER) is a very rare neoplasm
      with only 15 cases reported in the literature. Of those, only 1 case underwent a
      preoperative cytologic evaluation. We report a case of PER with diagnosis by
      imprint cytology. CASE: A 55-year-old woman presented with dysphagia of 2 months'
      duration associated with fatigue and weight loss. Clinical and diagnostic imaging
      investigations revealed a large, submucosal mass lesion located in the lower part
      of the esophagus. A bite biopsy of the esophageal mass was performed under
      esophagoscopy. Two imprint smears were made from the biopsied tissue fragment and
      stained with the May-Grunwald-Giemsa method. The smears revealed abundant,
      pleomorphic, malignant cells with basophilic cytoplasm. Some spindle-shaped
      cancer cells showed intracytoplasmic cross-striations, indicating a pleomorphic
      rhabdomyosarcoma, as confirmed by histologic and immunohistochemical studies of
      the biopsied tumor tissue and resected tumor. CONCLUSION: The presence of
      pleomorphic malignant cells with intracytoplasmic cross striations is a
      characteristic feature of pleomorphic rhabdomyosarcoma.

PMID- 16610694
TI  - Secondary infection and ischemic necrosis after fine needle aspiration for a
      painful papillary thyroid carcinoma: a case report.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) is often asymptomatic and rarely
      presents as a painful goiter. Further, the thyroid gland is not easily infected.
      Therefore, acute suppurative thyroiditis (AST) is unusual. PTC is also seldom
      combined with AST. We report a case of painful PTC with secondary infection after
      fine needle aspiration (FNA). CASE: A 19-year-old girl complained of a painful
      goiter without skin change after an episode of upper airway infection. PTC was
      diagnosed according to the FNA cytology (FNAC) at another hospital. The goiter
      became more painful after FNA. The patient's second FNAC at our hospital revealed
      only many polymorphonuclear leukocytes (PMNs). Antibiotic treatment ameliorated
      the pain, but the goiter persisted. The third FNAC revealed some PMNs and
      papillary carcinomatous cells. After total thyroidectomy, pathology revealed
      ischemic necrosis with a focal PMN aggregation around the needle track and
      papillary carcinomatous cells nearby. According to the time sequence, secondary
      infection after FNA was suspected. CONCLUSION: A painful goiter is an unusual
      presentation of PTC. Although FNAC is feasible for studying a thyroid lesion,
      malignant cells might be missed when secoandary injection and ischemic necrosis
      occur after FNA. Therefore, aseptic procedures are necessary to prevent bacteria
      from seeding into the thyroid.

PMID- 16610695
TI  - Tall cell variant of papillary carcinoma arising from a thyroglossal cyst: report
      of a case with diagnosis by fine needle aspiration cytology.
AB  - BACKGROUND: Papillary carcinoma arising from a thyroglossal duct cyst (TDC) is
      the most frequent malignancy arising from this embryologic remnant of the
      thyroglossal duct. The preoperative fine needle aspiration cytology (FNAC) of
      such neoplasms has rarely been cited. Approximately 170 TDC cases have been
      reported in the literature worldwide, diagnosed solely on histopathology. CASE: A
      63-year-old woman presented with an anterior midline neck mass of years'
      duration. A hypodense cyst was located at the level of the hyoid bone. FNAC of
      the midline neck mass showed bloody, mucoid material and numerous atypical,
      elongated cells. The aspirated material was reported as "papillary carcinoma
      possibly arising from the thyroglossal duct," and the diagnosis was confirmed by
      histopathologic investigation on resection material. CONCLUSION: Tall cell
      variant is a rare variant of papillary carcinoma and has a poor prognosis. The
      differential diagnosis includes Hurthle cell lesions, oncocytic papillary thyroid
      carcinoma and Warthin-like papillary carcinoma.

PMID- 16610696
TI  - Cytopathologic features of pituitary carcinoma with cervical vertebral bone
      metastasis: a case report.
AB  - BACKGROUND: Pituitary carcinomas are extremely rare tumors of the
      adenohypophysis. The presence of craniospinal and/or systemic extracranial
      metastases is the only reliable criterion for the diagnosis of pituitary
      carcinoma. To date, only 2 cases have been reported correctly by fine needle
      aspiration biopsy (FNAB). We present an additional case of pituitary carcinoma
      with FNAB features. CASE: A 60-year-old woman presented with clinical features of
      Cushing's disease and a pituitary tumor. She underwent transsphenoidal resection
      of the tumor. The initial diagnosis was an adrenocorticotrophic hormone (ACTH)
      producing invasive pituitary adenoma. The patient presented again with neck pain
      6 years after the operation. Magnetic resonance imaging revealed metastatic tumor
      masses at the level of C5-C6 of the cervical vertebrae. Intraoperative fine
      needle aspiration and incomplete excision of metastatic tumors were performed.
      Cytologically, tumor cells were composed of a combination of loose groups and
      single cells. Neoplastic cells had a relatively monotonous appearance and
      displayed characteristic neuroendocrine tumor features. Immunocytochemistry from
      cell block sections revealed AE1/ AE3, synaptophysin chromogranin A and ACTH
      positivity in the tumor cells. CONCLUSION: Pituitary carcinoma with extracranial
      systemic metastases demonstrates typical neuroendocrine features on fine needle
      aspiration. In the differential diagnosis, metastatic neuroendocrine carcinomas
      should be kept in mind. In the absence of sufficient clinical data, these 2
      entities cannot be distinguished correctly through the cytologic features.

PMID- 16610697
TI  - Diagnosis of disseminated rhinosporidiosis by fine needle aspiration cytology.

PMID- 16610698
TI  - Splenic fine needle aspiration and core biopsy.

PMID- 16610699
TI  - Metastatic warty (condylomatous) carcinoma of the uterine cervix associated with
      low-risk HPV type 6.

PMID- 16610700
TI  - Cytologic diagnosis of meningioma metastatic to the pleural cavity.

PMID- 16610701
TI  - Inflammation and cancer: the role of the immune response and angiogenesis.
AB  - The link with chronic inflammation and cancer has been recognized for certain
      cancers for several decades. However, only recently has the biology of chronic
      inflammation begun to be understood, to the point that it may play a major role
      in tumour development. The biology of chronic inflammation has many similarities
      with that of wound healing. In particular, local cell mediated immunity is
      attenuated and angiogenesis is increased along with other growth factors. When
      present long-term, this provides the ideal environment for mutated cells to be
      nurtured and escape immune surveillance. It is of note that this process still
      appears to take two or three decades, as witnessed by the close association
      between chronic ulcerative colitis and colon cancer as well as chronic hepatitis
      and hepatocellular carcinoma. Closer study of the inflammatory pathways show the
      close interaction with apoptosis and anti-apoptotic pathways, as well as the main
      tumour suppressor genes, such as p53, as well as a number of growth factors, such
      as the insulin-like growth factor. A full study of these processes reveals that
      there are key molecules in these pathways which may provide therapeutic as well
      as anti-inflammatory targets.

PMID- 16610702
TI  - Chronic inflammation and pathogenesis of GI and pancreatic cancers.
AB  - The pathogenesis of cancer represents a complex and multifactorial process
      requiring a number of acquired and genetic defects. It is becoming increasingly
      apparent that many cancers originate from a chronic inflammatory process. The
      topic of this review is the inflammatory response and development of
      gastrointestinal (GI) and pancreatic cancers. Here, we describe the development
      of various gastric colorectal and pancreatic cancers through an inflammatory
      process. The tumor microenvironment which predisposes to tissue destruction,
      subsequent attempts at healing and accumulation of cellular damage with loss of
      cell cycle control mechanisms is discussed. Components of the tumor
      microenvironment that are important in the final common pathway leading to cancer
      include the tumor stroma, tumor-associated macrophages, cytokines and chemokines
      and reactive oxygen and nitrogen species. Common signaling pathways that link
      inflammation with cancer are described and include the COX-2, NF-kappaB and
      phosphatidyl inositol 3-kinase (PI3K) pathways. Finally, therapies that can be
      directed to the inflammatory process as either treatment or prevention of these
      cancers will be discussed including novel inhibitors of signaling pathways which
      are currently in development.

PMID- 16610703
TI  - Cytokines, NF-kappaB, microenvironment, intestinal inflammation and cancer.
AB  - Inflammation and cancer have been viewed as closely linked for many years. This
      link is not merely a loose association but causative. In colorectal cancer (CRC),
      chronic inflammation as observed in inflammatory bowel (IBD) disease is a key
      predisposing factor and IBD-associated CRC comprises five percent of all CRCs.
      Although the molecular mechanisms linking IBD with CRC are not well understood,
      recent results obtained in preclinical models point to the transcription factor
      NF-kappaB as a central player. On the one hand, NF-kappaB regulates the
      expression of various cytokines and modulates the inflammatory processes in IBD.
      On the other, NF-kappaB stimulates the proliferation of tumor cells and enhances
      their survival through the regulation of anti-apoptotic genes. Furthermore, it
      has been clearly established that most carcinogens and tumor promoters activate
      NF-kappaB, while chemopreventive agents generally suppress this transcription
      factor. Actually, several lines of evidence suggest that activation of NF-kappaB
      may cause cancer. These include the finding that NF-kappaB genes can be
      oncogenes, and that this transcription factor controls apoptosis, cell-cycle
      progression and proliferation, and possibly also cell differentiation.

PMID- 16610704
TI  - Regulation of NF-kappaB transcriptional activity.
AB  - Nuclear factor kappaB (NF-kappaB) is regarded as a key regulator of inflammation;
      hence, several inflammatory diseases result from deregulation of NF-kappaB
      signaling. There is, however, also increasing evidence for a preponderant role of
      NF-kappaB in tumor development and progression. Constitutive activation of NF
      kappaB activity by signaling defects, mutations or chromosomal rearrangements can
      be found in a wide variety of cancers. Additionally, a causal link between
      inflammation and cancer has been noted, which makes NF-kappaB an interesting
      target for development of both anti-inflammatory and anti-cancer therapeutics.
      Here, we review current knowledge of NF-kappaB signal transduction, focusing on
      the regulation of its transcriptional activity by post-translational modification
      of the NF-kappaB subunits.

PMID- 16610705
TI  - The role of immune cells in the tumor microenvironment.
AB  - Interactions between tumor infiltrating leukocytes and tumor cells have been of
      great interest because of the possibility that immune cells either interfere with
      tumor progression or actively promote tumor growth. The tumor microenvironment is
      shaped by cells entering it, and their functions reflect the local conditions.
      Successive changes occurring at the tumor site during tumor progression resemble
      chronic inflammation. This chronic inflammatory reaction seems to be largely
      orchestrated by the tumor, and it seems to promote tumor survival. Molecular and
      cellular mechanisms linking the inflammatory reaction and cancer are emerging,
      and this review summarizes the current understanding of interactions between
      inflammatory and cancer cells in the tumor microenvironment.

PMID- 16610706
TI  - Tumor-microenvironment interactions: the selectin-selectin ligand axis in tumor
      endothelium cross talk.
AB  - Interactions of cancer cells with components of their microenvironment are
      crucial determinants in the decision making process which determines whether the
      cancer cells will progress towards a highly malignant phenotype or whether they
      will stay dormant or disappear altogether. The tumor microenvironment is composed
      of a plethora of soluble and cellular components. Many of these components
      deliver signals to tumor cells and thus modulate their phenotype thereby driving
      tumor progression. This chapter focuses on the interaction of tumor cells with
      endothelial cells through endothelial selectins and their fucosylated ligands
      expressed by the tumor cells. Comparisons are drawn between the utilization of
      this interaction axis by inflammatory leukocytes and by tumor cells.

PMID- 16610707
TI  - CD95L/FasL and TRAIL in tumour surveillance and cancer therapy.
AB  - The membrane-bound death ligands CD95L/FasL and TRAIL, which activate the
      corresponding death receptors CD95/Fas, TRAILR1 and TRAILR2, induce apoptosis in
      many tumour cells, but can also elicit an inflammatory response. This chapter
      focuses on the relevance of CD95L/FasL and TRAIL for the tumour surveillance
      function of natural killer cells and cytotoxic T-cells and discuss current
      concepts of utilizing these ligands in tumour therapy.

PMID- 16610708
TI  - Infection & neoplastic growth 101: the required reading for microbial pathogens
      aspiring to cause cancer.
AB  - The role of infectious agents in the development of cancer is well-established.
      For example, numerous RNA and DNA viruses express dedicated oncoproteins that are
      able to transform cells in vitro and induce rapid tumor formation in experimental
      animals. Curiously, these acutely-transforming viruses are seldom associated with
      naturally occurring neoplasms of humans or animals. Conversely, the microbial
      pathogens that are linked to cancers in natural hosts rarely encode acutely
      transforming proteins. Moreover, they tend to down-regulate most of their genes
      except for genes affecting cell survival, often via the NF-kappaB pathway. This
      allows the pre-neoplastic cell to avoid triggering cytotoxic immunity and the
      ensuing acute inflammation. These host responses not only kill tumor cells
      directly, but also strongly suppress the development of new blood vessels
      (neovascularization), which is absolutely essential for neoplastic growth.
      Chronic inflammation, on the other hand, promotes neoplastic cell growth and may
      even be conducive to neovascularization. Thus, cancer-associated microbial
      pathogens must follow the "less is more" principle. According to this principle,
      only minor perturbations in cell proliferation and death are tolerated by the
      host, but in the long run, they are all that is necessary for tumorigenesis.

PMID- 16610709
TI  - Cytokines as mediators and targets for cancer cachexia.
AB  - The cachexia syndrome, characterized by a marked weight loss, anorexia, asthenia
      and anaemia, is invariably associated with the growth of a tumour and leads to a
      malnutrition status caused by the induction of anorexia or decreased food intake.
      In addition, the competition for nutrients between the tumour and the host
      results in a state of accelerated catabolism, which promotes severe metabolic
      disturbances in the patient. The search for the cachectic factor(s) started a
      long time ago, and many scientific and economic efforts have been devoted to its
      discovery, but we are still a long way from a complete answer. The present review
      aims to evaluate the different molecular mechanisms and catabolic mediators (both
      humoural and tumoural) that are involved in cancer cachexia and to discuss their
      potential as targets for future clinical investigations.

PMID- 16610710
TI  - Targeting NF-kappaB in anticancer adjunctive chemotherapy.
AB  - After more than three decades of its declaration, the war against cancer still
      appears far from being won. Although there have been decisive victories in a few
      battles, such as the one against testicular cancer, the overall result is
      sobering. Hopes for an imminent cure had been raised among the public by the
      promises of molecular biology, combinatorial chemistry and high-throughput
      screening. These promises have manifested themselves in the widely proclaimed
      strategy of rationally targeted anticancer drug discovery, which may be
      summarized as the 'one-gene-one target-one drug' approach. Over the years,
      however, it has gradually become clear that, in most cases, treatment of cancer
      with a single drug may at best delay progression of the disease but is unlikely
      to lead to a cure. Thus, it appears that rationally targeted monotherapy will
      have to be replaced by rationally targeted combination therapy. Inhibitors of NF
      kappaB look likely to become an important weapon in the anticancer combination
      therapy arsenal.

PMID- 16610711
TI  - A novel polymeric coating for enhanced ultrasound visibility of medical devices.
AB  - A dynamic novel coating, consisting of a hydrophilic polymeric matrix and a
      bubbling agent, has been developed for precise entry and positioning of needles,
      and accurate collection of biopsy samples. These coated biopsy needles have been
      successfully used in in vitro trials. The results are discussed here. Potential
      application areas include vascular, cardiovascular and orthopaedics.

PMID- 16610712
TI  - Pills and potions: will transdermal patches or needle-free injection ever replace
      them?
AB  - Just over two years ago, it was forecast that transdermal patches would be one of
      the fastest growing sectors of the drug delivery market. Has the promise of new
      technology been fulfilled or do pills and potions taken orally still dominate the
      market? This review will look at the most recent developments and update the
      technology roadmaps in this US dollar 40-billion market.

PMID- 16610713
TI  - Evaluating new hypodermic and intradermal injection devices.
AB  - The wicking spear gravimetric method was selected as the easier and the most
      consistent method for fluid leakage collection. The kit uses the glass sample
      collection tube to store the wicking spears before and after fluid leakage
      collection. It has been shown to provide reliable equipment for wicking spear
      intermediate storage and shipment to central laboratories for weight/mass
      measurements. Weighting the collection tubes with wicking spear inside, in a
      central laboratory in a batch fashion, before and after fluid collection,
      contributes to minimising operator and balance errors on method accuracy. The
      volume detection threshold is below 2 microL and the measurement error, even
      after 12 days of storage at room temperature, is below 1 microL, which is
      considered not to be clinically relevant.

PMID- 16610714
TI  - Drive systems for miniature pumps.
AB  - The huge variety of medical applications demands a similar number of pumps
      customised for optimum performance in each application. One important element
      that has a significant influence on the overall performance of a pump is its
      drive system. This article describes the typical drive systems employed in
      miniature pumps and highlights the consequences of selecting one type over
      another.

PMID- 16610715
TI  - The Korean stem cell fiasco: shifting the focus.
AB  - No one could have failed to have seen the dramatic headlines surrounding
      Professor Woo Suk Hwang of the Seoul National University. Hwang claimed first
      place in the race to create patient-specific stem cells from cloned human
      embryos, only to be discredited shortly afterwards. This article discusses
      whether such high-profile negative publicity has damaged the regenerative
      medicine industry in general or whether it has merely shifted the stem cell focus
      away from South Korea.

PMID- 16610716
TI  - US guidance on formatting 510(k)s.
AB  - There is no official form for submitting a United States premarket notification
      or 510(k) submission. A recent Food and Drug Administration guidance document
      describes the manner in which this type of premarket submission should be
      formatted. This article discusses this document and so me important aspects of
      the 510(k) process.

PMID- 16610717
TI  - Designing screened enclosures: Part II.
AB  - Techniques to achieve cost-effective emissions and immunity screening solutions
      that meet electromagnetic compatibility requirements were provided in Part I of
      this article, which covered design options for seams and gaskets. Part II
      continues with a discussion of materials compatibility, corrosion and apertures.

PMID- 16610718
TI  - Implementing continuous improvement.
AB  - Companies should employ Six Sigma to improve their decision-making, gain better
      control and improve business efficiency, says one advocate.

PMID- 16610719
TI  - Think like the body does. Welcome to the ultimate performance machine.

PMID- 16610720
TI  - Let me die. Honoring people's other right.

PMID- 16610721
TI  - Burn, baby, burn. Chemical causes distress in the home.

PMID- 16610722
TI  - Are you a meeting "master"? Making meetings make sense.

PMID- 16610723
TI  - Rebuilding from the (high) ground up. New Orleans EMS six months later.

PMID- 16610724
TI  - The methamphetamine crisis. What EMS providers need to know to stay safe and
      treat patients.
AB  - Methamphetamine is a highly addictive drug that is an increasingly recognized
      problem for emergency responders in all areas of the country. Any clandestine
      drug lab is a hazardous materials incident and crime scene. Enter a clandestine
      drug lab only if you have proper training and equipment--do not become a victim.
      Methamphetamine users are generally paranoid, agitated and anxious, and may
      become violent during assessment and treatment. Children living at a meth lab are
      at greater risk for physical and/or sexual abuse and neglect.

PMID- 16610725
TI  - The making of a marketer. How states are stepping in to help volunteer
      recruitment.

PMID- 16610726
TI  - Beyond the basics: right vs. left heart failure.
AB  - Heart failure is a pathophysiologic cascade that, if improperly identified and
      managed, may lead to death. If heart failure is identified early enough,
      development of irreversible end-stage heart failure may be avoided. The goal of
      the prehospital care provider in managing heart failure is directed at
      maintenance of adequate cellular oxygenation, reduction of preload and afterload
      to improve forward blood flow, and, ultimately, improve cardiac output.

PMID- 16610727
TI  - Improving the hemodynamics of CPR. AHA guidelines support timely and effective
      CPR.
AB  - More research is needed to improve our understanding of what constitutes the most
      effective method of cardiopulmonary resuscitation; however, we know more now than
      ever in the history of medicine. We know that CPR is more than simply pushing on
      the chest and defibrillating the heart. We know that there exists an optimal
      physiologic condition to facilitate successful resuscitation that relies on
      quality coronary and cerebral artery perfusion and preparation of the heart
      before defibrillation. There are many questions yet to be answered, such as how
      long defibrillation should be delayed following CPR, which devices or techniques
      provide the most effective CPR, and what are the most effective ratios of
      compression and ventilation? The answer may lie within a combination of
      approaches using multiple devices and techniques simultaneously in an attempt to
      meet the goals for performing the most effective CPR. What is clear is that the
      science of cardiac arrest is maturing, and what began in the early ages as an act
      of faith and desperation has now become grounded in logical reason and
      understanding of the physiology of cardiac arrest and the hemodynamics of CPR.

PMID- 16610728
TI  - Does vasopressin improve survival?

PMID- 16610729
TI  - Distinguishing wide complex tachycardia: a prehospital perspective.
AB  - It is important to mention that not all rhythms are textbook presentations.
      Certainty exists only in degrees. While the diagnostic clues offered in this
      article may help to increase certainty as it pertains to diagnosing a WCT, they
      are not a replacement for continued investigation and discovery regarding cardiac
      anatomy, physiology and pathophysiology, nor can they be exacting and precise
      when taken as isolated events. But taken as a whole these clues can build a
      convincing case for correctly differentiating and treating a WCT. Diagnosing and
      treating WCTs can be challenging, but with the proper tools, an accurate
      diagnosis is well within the reach of prehospital care providers (see Table II
      for a concise summary of electrographical and clinical clues).

PMID- 16610730
TI  - A burning issue: burns and other triggers in pemphigus.

PMID- 16610731
TI  - What is your diagnosis? Diagnosis: Seabather's eruption.

PMID- 16610732
TI  - Botanical briefs: ylang-ylang oil--extracts from the tree Cananga odorata.

PMID- 16610733
TI  - Clinical significance of brand versus generic formulations: focus on oral
      minocycline.
AB  - Minocycline is an oral antibiotic widely prescribed throughout the world,
      primarily for the treatment of acne vulgaris; other uses include the treatment of
      rosacea and perioral dermatitis. In the United States, Propionibacterium acnes
      resistance is lowest with minocycline compared with other tetracyclines and with
      erythromycin. The availability of generic formulations of minocycline has created
      confusion regarding the clinical significance of brand versus generic minocycline
      products. This article reviews available data on minocycline use for acne
      vulgaris and discusses a patented brand of minocycline versus generic
      formulations, including evaluations of pharmacologic activity and safety.

PMID- 16610734
TI  - Primary cutaneous adenoid cystic carcinoma: a case report and literature review.
AB  - Primary cutaneous adenoid cystic carcinoma (ACC) is a rare tumor, with less than
      50 cases reported to date. We report an additional case of primary cutaneous ACC
      arising on the scalp of a 57-year-old woman. The clinical presentation,
      histologic findings, and subsequent treatment are described. A brief review of
      the literature is provided.

PMID- 16610735
TI  - Pemphigus vulgaris induced by electrical injury.
AB  - Pemphigus refers to a group of autoimmune blistering diseases that affect the
      skin and mucous membranes. Pemphigus may be induced following exposure to various
      exogenous agents, including thermal burns, drugs, infectious agents, and
      neoplasms, as well as UV, ionizing, and x-ray irradiation. We report a case of a
      28-year-old man with pemphigus vulgaris (PV) induced by a severe electrical
      injury. Approximately one month after the electrical injury, he began to develop
      recurrent painful oral ulcers; one year later, he began to develop cutaneous
      bullae. Results of a histopathologic examination and immunofluorescence studies
      were diagnostic of PV The primary mechanisms of high-voltage electrical injury
      involve electroporation, electroconformational protein denaturation, and both
      joule and dielectric heating. Cutaneous electrical injury ultimately results in
      the destruction of cells with release of their cellular constituents. Through
      these mechanisms, desmoglein 3 (Dsg3) may be released and become available to the
      immune system, which potentially leads to an autoantibody response and the
      subsequent development of PV.

PMID- 16610736
TI  - Pityriasis rosea-like eruption due to bismuth.
AB  - We report a case of bismuth-induced pityriasis rosea-like drug eruption. Although
      historical accounts of bismuth hypersensitivity exist, contemporary reports are
      lacking. Given the frequency of bismuth administration, a modern review of this
      phenomenon would seem prudent.

PMID- 16610737
TI  - Disseminated vitiligo associated with AIDS.
AB  - We report a case of vitiligo arising one year after human immunodeficiency virus
      (HIV) seropositivity but before clinical onset of acquired immunodeficiency
      syndrome (AIDS). To our knowledge, this specific time sequence has not been
      described. Generalization of such lesions began during a period of medical
      noncompliance, increasing viral load, rising CD8+ count, and markedly decreased
      CD4+ count. These findings suggest new mechanisms of autoimmune and infectious
      pathogenesis.

PMID- 16610738
TI  - Community-based trial of a triple-combination agent for the treatment of facial
      melasma.
AB  - Melasma is a common hyperpigmentation disorder that is frequently recalcitrant to
      treatment. An 8-week, multicenter, open-label, community-based study evaluated a
      new therapeutic approach that combines tretinoin 0.05%, hydroquinone 4.0%, and
      fluocinolone acetonide 0.01% (RA+HQ+FA) in a hydrophilic cream formulation. The
      trial enrolled 1290 patients of diverse races/ethnicities with a full range of
      Fitzpatrick skin types (I through VI). The mean Melasma Area and Severity Index
      (MASI) decreased significantly at both weeks 4 and 8 compared with baseline in
      the overall study population and across all Fitzpatrick skin types and
      races/ethnicities (P<.0001). The mean MASI darkness and homogeneity scores
      likewise fell significantly at weeks 4 and 8 in all facial regions involved
      (forehead, right and left malar regions, and chin) and in all Fitzpatrick skin
      types (P<.0001). By week 8, investigators' global evaluations showed that 75% of
      patients had "moderate or marked improvement" or were "almost clear" or "clear."
      The study medication was found to be safe and well tolerated. The results of this
      study demonstrate that RA+HQ+FA produces significant rapid improvement of melasma
      across the range of patients seen in daily practice, including whites, Hispanics,
      blacks, Asians, American Indians, Alaskan natives, and Pacific Islanders.

PMID- 16610739
TI  - Sinorhizobium meliloti differentiation during symbiosis with alfalfa: a
      transcriptomic dissection.
AB  - Sinorhizobium meliloti is a soil bacterium able to induce the formation of
      nodules on the root of specific legumes, including alfalfa (Medicago sativa).
      Bacteria colonize nodules through infection threads, invade the plant
      intracellularly, and ultimately differentiate into bacteroids capable of reducing
      atmospheric nitrogen to ammonia, which is directly assimilated by the plant. As a
      first step to describe global changes in gene expression of S. meliloti during
      the symbiotic process, we used whole genome microarrays to establish the
      transcriptome profile of bacteria from nodules induced by a bacterial mutant
      blocked at the infection stage and from wild-type nodules harvested at various
      timepoints after inoculation. Comparison of these profiles to those of cultured
      bacteria grown either to log or stationary phase as well as examination of a
      number of genes with known symbiotic transcription patterns allowed us to
      correlate global gene-expression patterns to three known steps of symbiotic
      bacteria bacteroid differentiation, i.e., invading bacteria inside infection
      threads, young differentiating bacteroids, and fully differentiated, nitrogen
      fixing bacteroids. Finally, analysis of individual gene transcription profiles
      revealed a number of new potential symbiotic genes.

PMID- 16610740
TI  - Spontaneous root-nodule formation in the model legume Lotus japonicus: a novel
      class of mutants nodulates in the absence of rhizobia.
AB  - Root-nodule development in legumes is an inducible developmental process
      initially triggered by perception of lipochitin-oligosaccharide signals secreted
      by the bacterial microsymbiont. In nature, rhizobial colonization and invasion of
      the legume root is therefore a prerequisite for formation of nitrogen-fixing root
      nodules. Here, we report isolation and characterization of chemically induced
      spontaneously nodulating mutants in a model legume amenable to molecular
      genetics. Six mutant lines of Lotus japonicus were identified in a screen for
      spontaneous nodule development under axenic conditions, i.e., in the absence of
      rhizobia. Spontaneous nodules do not contain rhizobia, bacteroids, or infection
      threads. Phenotypically, they resemble ineffective white nodules formed by some
      bacterial mutants on wild-type plants or certain plant mutants inoculated with
      wild-type Mesorhizobium loti. Spontaneous nodules formed on mutant lines show the
      ontogeny and characteristic histological features described for rhizobia-induced
      nodules on wild-type plants. Physiological responses to nitrate and ethylene are
      also maintained, as elevated levels inhibit spontaneous nodulation. Activation of
      the nodule developmental program in spontaneous nodules was shown for the early
      nodulin genes Enod2 and Nin, which are both upregulated in spontaneous nodules as
      well as in rhizobial nodules. Both monogenic recessive and dominant spontaneous
      nodule formation (snf) mutations were isolated in this mutant screen, and map
      positions were determined for three loci. We suggest that future molecular
      characterization of these mutants will identify key plant determinants involved
      in regulating nodulation and provide new insight into plant organ development.

PMID- 16610741
TI  - Heterologous expression of the Mi-1.2 gene from tomato confers resistance against
      nematodes but not aphids in eggplant.
AB  - The Mi-1.2 gene in tomato (Solanum lycopersicum) is a member of the nucleotide
      binding leucine-rich repeat (NBLRR) class of plant resistance genes, and confers
      resistance against root-knot nematodes (Meloidogyne spp.), the potato aphid
      (Macrosiphum euphorbiae), and the sweet potato whitefly (Bemisia tabaci). Mi-1.2
      mediates a rapid local defensive response at the site of infection, although the
      signaling and defensive pathways required for resistance are largely unknown. In
      this study, eggplant (S. melongena) was transformed with Mi-1.2 to determine
      whether this gene can function in a genetic background other than tomato.
      Eggplants that carried Mi-1.2 displayed resistance to the root-knot nematode
      Meloidogyne javanica but were fully susceptible to the potato aphid, whereas a
      susceptible tomato line transformed with the same transgene was resistant to
      nematodes and aphids. This study shows that Mi-1.2 can confer nematode resistance
      in another Solanaceous species. It also indicates that the requirements for Mi
      mediated aphid and nematode resistance differ. Potentially, aphid resistance
      requires additional genes that are not conserved between tomato and eggplant.

PMID- 16610742
TI  - MgSlt2, a cellular integrity MAP kinase gene of the fungal wheat pathogen
      Mycosphaerella graminicola, is dispensable for penetration but essential for
      invasive growth.
AB  - Among expressed sequence tag libraries of Mycosphaerella graminicola isolate
      IPO323, we identified a full-length cDNA clone with high homology to the mitogen
      activated protein (MAP) kinase Slt2 in Saccharomyces cerevisiae. This MAP kinase
      consists of a 1242-bp open reading frame, and encodes a 414-amino-acid protein.
      We designated this homolog MgSlt2, generated MgSlt2 knockout strains in M.
      graminicola isolate IPO323, and found several altered phenotypes in vitro as well
      as in planta. In yeast glucose broth, MgSlt2 disruptants showed a defective
      polarized growth in the tip cells upon aging, causing substantial local
      enlargements culminating in large swollen cells containing two to four nuclei.
      The MgSlt2 disruptants showed a significantly increased sensitivity to several
      fungicides, including miconazole (2x), bifonazole (>4x), imazalil (5x), and
      cyproconazole (10x), and were hypersensitive to glucanase. Unlike the wild type,
      MgSlt2 disruptants did not produce aerial mycelia and did not melanize on potato
      dextrose agar. Although cytological analysis in planta showed normal penetration
      of wheat stomata by the germ tubes of the MgSlt2 disruptants, subsequently formed
      hyphal filaments frequently were unable to branch out and establish invasive
      growth resulting in highly reduced virulence, and prevented pycnidia formation.
      Therefore, we conclude that MgSlt2 is a new pathogenicity factor in M.
      graminicola.

PMID- 16610743
TI  - EIL2 transcription factor and glutathione synthetase are required for defense of
      tobacco against tobacco blue mold.
AB  - In order to identify tobacco (Nicotiana megalosiphon) genes involved in broad
      spectrum resistance to tobacco blue mold (Peronospora hyoscyami f. sp. tabacina),
      suppression subtractive hybridization was used to generate cDNA from transcripts
      that are differentially expressed during an incompatible interaction. After
      differential screening by membrane-based hybridization, clones corresponding to
      182 differentially expressed genes were selected, sequenced, and analyzed. The
      cDNA collection comprised a broad repertoire of genes associated with various
      processes. Northern blot analysis of a subset of these genes confirmed the
      differential expression patterns between the compatible and incompatible
      interaction. Subsequent virus-induced gene silencing (VIGS) of four genes that
      were found to be differentially induced was pursued. While VIGS of a lipid
      transfer protein gene or a glutamate decarboxylase gene in Nicotiana megalosiphon
      did not affect blue mold resistance, silencing of an EIL2 transcription factor
      gene and a glutathione synthetase gene was found to compromise the resistance of
      Nicotiana megalosiphon to P. hyoscyami f. sp. tabacina. Potentially, these genes
      can be used to engineer resistance in blue mold-susceptible tobacco cultivars.

PMID- 16610744
TI  - Transcriptome analysis of the barley-Fusarium graminearum interaction.
AB  - Fusarium head blight (FHB) of barley (Hordeum vulgare L.) is caused by Fusarium
      graminearum. FHB causes yield losses and reduction in grain quality primarily due
      to the accumulation of trichothecene mycotoxins such as deoxynivalenol (DON). To
      develop an understanding of the barley-F. graminearum interaction, we examined
      the relationship among the infection process, DON concentration, and host
      transcript accumulation for 22,439 genes in spikes from the susceptible cv. Morex
      from 0 to 144 h after F. graminearum and water control inoculation. We detected
      467 differentially accumulating barley gene transcripts in the F. graminearum
      treated plants compared with the water control-treated plants. Functional
      annotation of the transcripts revealed a variety of infection-induced host genes
      encoding defense response proteins, oxidative burst-associated enzymes, and
      phenylpropanoid pathway enzymes. Of particular interest was the induction of
      transcripts encoding potential trichothecene catabolic enzymes and transporters,
      and the induction of the tryptophan biosynthetic and catabolic pathway enzymes.
      Our results define three stages of E graminearum infection. An early stage,
      between 0 and 48 h after inoculation (hai), exhibited limited fungal development,
      low DON accumulation, and little change in the transcript accumulation status. An
      intermediate stage, between 48 and 96 hai, showed increased fungal development
      and active infection, higher DON accumulation, and increased transcript
      accumulation. A majority of the host gene transcripts were detected by 72 hai,
      suggesting that this is an important timepoint for the barley-F. graminearum
      interaction. A late stage also identified between 96 and 144 hai, exhibiting
      development of hyphal mats, high DON accumulation, and a reduction in the number
      of transcripts observed. Our study provides a baseline and hypothesis-generating
      dataset in barley during F. graminearum infection and in other grasses during
      pathogen infection.

PMID- 16610745
TI  - Biocontrol of avocado dematophora root rot by antagonistic Pseudomonas
      fluorescens PCL1606 correlates with the production of 2-hexyl 5-propyl
      resorcinol.
AB  - A collection of 905 bacterial isolates from the rhizospheres of healthy avocado
      trees was obtained and screened for antagonistic activity against Dematophora
      necatrix, the cause of avocado Dematophora root rot (also called white root rot).
      A set of eight strains was selected on the basis of growth inhibitory activity
      against D. necatrix and several other important soilborne phytopathogenic fungi.
      After typing of these strains, they were classified as belonging to Pseudomonas
      chlororaphis, Pseudomonas fluorescens, and Pseudomonas putida. The eight
      antagonistic Pseudomonas spp. were analyzed for their secretion of hydrogen
      cyanide, hydrolytic enzymes, and antifungal metabolites. P. chlororaphis strains
      produced the antibiotic phenazine-1-carboxylic acid and phenazine-1-carboxamide.
      Upon testing the biocontrol ability of these strains in a newly developed avocado
      D. necatrix test system and in a tomato-F oxysporum test system, it became
      apparent that P. fluorescens PCL1606 exhibited the highest biocontrol ability.
      The major antifungal activity produced by strain P. fluorescens PCL1606 did not
      correspond to any of the major classes of antifungal antibiotics produced by
      Pseudomonas biocontrol strains. This compound was purified and subsequently
      identified as 2-hexyl 5-propyl resorcinol (HPR). To study the role of HPR in
      biocontrol activity, two Tn5 mutants of P. fluorescens PCL1606 impaired in
      antagonistic activity were selected. These mutants were shown to impair HRP
      production and showed a decrease in biocontrol activity. As far as we know, this
      is the first report of a Pseudomonas biocontrol strain that produces HPR in which
      the production of this compound correlates with its biocontrol activity.

PMID- 16610746
TI  - Integrated signaling network involving calcium, nitric oxide, and active oxygen
      species but not mitogen-activated protein kinases in BcPG1-elicited grapevine
      defenses.
AB  - We have already reported the identification of the endopolygalacturonase 1
      (BcPG1) from Botrytis cinerea as a potent elicitor of defense responses in
      grapevine, independently of its enzymatic activity. The aim of the present study
      is the analysis of the signaling pathways triggered by BcPG1 in grapevine cells.
      Our data indicate that BcPG1 induces a Ca2+ entry from the apoplasm, which
      triggers a phosphorylation-dependent nitric oxide (NO) production via an enzyme
      probably related to a NO synthase. Then NO is involved in (i) cytosolic calcium
      homeostasis, by activating Ca2+ release from internal stores and regulating Ca2+
      fluxes across the plasma membrane, (ii) plasma membrane potential variation,
      (iii) the activation of active oxygen species (AOS) production, and (iv) defense
      gene expression, including phenylalanine ammonia lyase and stilbene synthase,
      which encode enzymes responsible for phytoalexin biosynthesis. Interestingly
      enough, mitogen-activated protein kinase (MAPK) activation is independent of this
      regulation pathway that closely connects Ca2+, NO, and AOS.

PMID- 16610747
TI  - A class 1 hemoglobin gene from Alnus firma functions in symbiotic and
      nonsymbiotic tissues to detoxify nitric oxide.
AB  - Actinorhizal symbiosis is as important in biological nitrogen fixation as legume
      rhizobium symbiosis in the global nitrogen cycle. To understand the function of
      hemoglobin (Hb) in actinorhizal symbiosis, we characterized a Hb of Alnus firma,
      AfHb1. A cDNA that encodes nonsymbiotic Hb (nonsym-Hb) was isolated from a cDNA
      library of A. firma nodules probed with LjHb1, a nonsym-Hb of Lotus japonicus. No
      homolog of symbiotic Hb (sym-Hb) could be identified by screening in the cDNA
      library or by polymerase chain reaction (PCR) using degenerate primers for other
      sym-Hb genes. The deduced amino acid sequence of AfHb1 showed 92% sequence
      similarity with a class 1 nonsym-Hb of Casuarina glauca. Quantitative reverse
      transcriptase-PCR analysis showed that AfHb1 was expressed strongly in the
      nodules and enhanced expression was detected under cold stress but not under
      hypoxia or osmotic stress. Moreover, AfHfb1 was strongly induced by the
      application of nitric oxide (NO) donors, and the application of a NO scavenger
      suppressed the effect of NO donors. Acetylene reduction was strongly inhibited by
      the addition of NO donors. AfHb1 may support the nitrogen fixation ability of
      members of the genus Frankia as a NO scavenger.

PMID- 16610748
TI  - Population behavior analysis of dspE and pelD regulation in Erwinia chrysanthemi
      3937.
AB  - Erwinia chrysanthemi 3937 (Ech3937) is a phytopathogenic bacterium with a wide
      host range. The pectinolytic enzymes secreted by the bacterium and the type III
      secretion system (T3SS) are essential for full virulence. We used the green
      fluorescent protein gene as a reporter to investigate the expression of dspE (a
      putative T3SS effector) and pelD (a major pectin-degrading enzyme) in populations
      of Ech3937 under different conditions. Gene expression was analyzed by measuring
      the fluorescence intensity of individual cells with a fluorescence-activated cell
      sorter. Ech3937 dspE was induced in minimal medium (MM) with only a portion of
      Ech3937 cells (43.03%) expressing dspE after 12 h of culture. The nutrient-rich
      King's medium B did not fully eliminate the expression of dspE; a small
      percentage of Ech3937 cells (5.55%) was able to express dspE after 12 h of
      culture in this medium. In all, 68.95% of Ech3937 cells expressed pelD after 12 h
      of culture in MM supplemented with polygalacturonic acid (PGA). However, 96.34%
      of Echl31 cells (an hrpL deletion mutant of Ech3937) expressed pelD after 12 h of
      culture in MM supplemented with PGA. In potato tubers, 6.32% of the bacterial
      cells expressed dspE 2 h after inoculation, whereas only 0.25% of the cells
      expressed pelD. However, after 24 h, the percentage of cells expressing pelD
      (68.48%) was approximately 3.5 times that of cells expressing dspE (19.39%). In
      contrast to potato tubers, similar proportion of Ech3937 cells expressing dspE
      (39.34%) and pelD (40.30%) were observed in Chinese cabbage 24 h after
      inoculation. From promoter activity and real-time quantitative results, the
      expression of pelD in Ech3937 was demonstrated to be downregulated by HrpL in MM
      supplemented with PGA.

PMID- 16610749
TI  - Special section: the power of choice: autonomy, informed consent, and the right
      to refuse.

PMID- 16610750
TI  - Questioning our principles: anthropological contributions to ethical dilemmas in
      clinical practice.

PMID- 16610751
TI  - Should parental refusals of newborn screening be respected?

PMID- 16610752
TI  - Has the emphasis on autonomy gone too far? Insights from Dostoevsky on parental
      decisionmaking in the NICU.

PMID- 16610753
TI  - The need for informed consent: lessons from the ancient Greeks.

PMID- 16610754
TI  - Gamete retrieval after death or irreversible unconsciousness: what counts as
      informed consent?

PMID- 16610755
TI  - CQ sources/bibliography.

PMID- 16610756
TI  - A paradox out of context: Harris and Holm on the precautionary principle.

PMID- 16610757
TI  - A child's life or a "'little bit of torture"? state-sanctioned violence and
      dignity.

PMID- 16610758
TI  - Participation in torture and interrogation: an inexcusable breach of medical
      ethics.

PMID- 16610759
TI  - Rounding: a model for consultation and training whose time has come.

PMID- 16610760
TI  - Antisense treatments for biothreat agents.
AB  - Antisense oligomers (ASOs) represent a promising technology to treat viral and
      bacterial infections, and have already been shown to be successful against a
      variety of pathogens in cell culture studies and nonhuman primate models of
      infection. For these reasons, antisense technologies are being pursued as
      treatments against biothreat agents such as Ebola virus, dengue virus and
      Bacillus anthracis. Several generations of modified oligonucleotides have been
      developed to maximize nuclease resistance, target affinity, potency, cell entry,
      and other pharmacokinetic properties. First-generation ASOs contain
      phosphorothioate modifications to increase stability through nuclease resistance.
      Further chemical modifications in second-generation ASOs include 2'-O-methyl and
      2'-O-methoxy-ethyl oligos, which increase nuclease resistance and oligo:RNA
      binding affinities. Third-generation ASOs contain a variety of chemical
      modifications that enhance stability, affinity and bioavailability. A fourth
      class of oligonucleotide-based compounds consists of small interfering RNAs,
      which have recently become widely used for gene knockdown in vitro and in vivo.
      This review focuses on the third-generation phosphorodiamidate morpholino
      oligomers, which are nonionic and contain a morpholine ring instead of a ribose,
      as well as phosphorodiamidate linkages in place of phosphorothioates. Multiple
      antisense oligomer-based therapeutics are being developed for use against
      biothreat agents, and antisense drugs will likely become a critical member of our
      arsenal in the defense against highly pathogenic, emerging or genetically
      engineered pathogens.

PMID- 16610761
TI  - Nucleic-acid-based antiviral agents against positive single-stranded RNA viruses.
AB  - Positive single-stranded RNA viruses constitute a broad and prevalent group of
      pathogens that threaten human health and life worldwide. While effective vaccines
      have been developed for some, such as poliovirus and hepatitis A, others such as
      coxsackievirus, severe acute respiratory syndrome coronavirus (SARS-CoV) and West
      Nile virus have no accredited drug treatments. Antisense technologies, which
      encompass small interfering RNA, antisense oligonucleotides, ribozymes and their
      chemically modified analogs, involve small sequence-specific nucleic-acid-based
      molecules that inhibit viral replication at the level of translation. Many
      antisense oligomers are proven antiviral agents in vitro. In this review, iwe
      provide an overview of the antiviral antisense field, highlighting specific
      studies of interest over the past several years, using our experience with
      coxsackievirus B3 as a reference point. Overall, both the challenges and
      successes of existing antisense therapies for positive single-stranded RNA
      viruses can be paralleled to those for other virus groups, and vice versa.

PMID- 16610762
TI  - Oligonucleotide analogs as antiviral agents.
AB  - The recent availability of a wider range of oligonucleotide analogs has
      stimulated renewed interest in their application as potential antiviral agents
      through a variety of mechanisms. These mechanisms include RNase H-mediated
      antisense, steric block antisense and small interfering RNA targeting viral RNAs,
      but also other mechanisms, including blockage of virus uptake by cells and the
      stimulation of a Toll-like receptor-9-dependent immune response by CpG
      oligonucleotides.

PMID- 16610763
TI  - Antiviral applications of RNAi.
AB  - RNA interference (RNAi) is a natural mechanism by which small interfering RNA
      (siRNA) operates to specifically and potently downregulate the expression of a
      target gene. This downregulation has been thought to predominantly function at
      the level of mRNA, as post-transcriptional gene silencing. The discovery that
      siRNAs can suppress gene expression at the level of transcription, that is,
      transcriptional gene silencing, has created a major paradigm shift in mammalian
      RNAi. These findings significantly broaden the role that RNA, specifically siRNA
      and potentially microRNA, plays in the regulation of gene expression, as well as
      the breadth of potential siRNA target sites. Indeed, the specificity and
      simplicity of design makes the use of siRNAs to target and suppress virtually any
      gene of interest a realized technology. Furthermore, since siRNAs are small
      nucleic acid reagents, they are unlikely to elicit an immune response,
      theoretically making them good therapeutics. The development, delivery and
      potential therapeutic use of antiviral siRNAs in treating viral infections and
      emerging viral threats are reviewed.

PMID- 16610764
TI  - Nucleic acid aptamers as adjuncts to vaccine development.
AB  - Nucleic acid 'aptamers', a term derived from the Latin word aptus, 'to fit', are
      RNA or DNA oligonucleotides that conform to the three-dimensional structure of a
      selected protein, peptide or small molecules' functional moiety. The 'lock and
      key' relationship between aptamers and their binding partner permits distinction
      between closely related but non-identical members of a protein family, or between
      different functional or conformational states of the same protein. This, along
      with other properties, separates aptamers from antibodies--the most popular class
      of molecular recognition tool for the past three decades. Despite the chemical,
      biological and manufacturing advantages offered by nucleic acid aptamers in a
      wide variety of conditions, and their generation against a range of clinically
      relevant targets, including growth factors, transcription factors and coagulation
      proteins, by two dozen or more companies devoted to the technology platform, only
      one aptamer, developed for the treatment of wet age-related macular degeneration,
      is currently available for use in humans. Nevertheless, phase I and II clinical
      trials for several indications are proceeding with considerable enthusiasm. The
      potential application of nucleic acid aptamers in novel arenas, including
      molecular imaging, vaccine development, immunomodulation, decoys for natural RNA
      binding events, antiviral therapeutics and both cancer prophylaxis and treatment,
      is emerging with a pioneering mentality destined to change the paradigm of
      patient care.

PMID- 16610765
TI  - Modification of pre-mRNA processing: application to dystrophin expression.
AB  - Antisense oligonucleotides are emerging as exciting therapeutic agents with the
      potential to overcome disease-causing mutations in the dystrophin gene. The size
      and complexity of the dystrophin gene allows for intervention during pre-mRNA
      processing, where selected exon excision can remove nonsense mutations or restore
      the reading frame disrupted by genomic deletions or duplications. This review
      summarizes some of the events leading up to forthcoming clinical trials in 2006,
      and speculates on some of the challenges facing targeted exon skipping as a
      therapy for Duchenne muscular dystrophy.

PMID- 16610766
TI  - The influence of chemical structure of DNA and other oligomer
      radiopharmaceuticals on tumor delivery.
AB  - Deoxyribose nucleic acids (DNAs) and their many chemically distinct synthetic
      analogs (collectively 'oligomers') provide a rich variety of molecules with
      different properties, each attractive as a potential drug. The main impediment to
      the successful development of these drugs is often identified as its delivery.
      Delivery usually refers to the cell membrane transport required to bring the
      oligomer into the cytoplasm or nucleus and therefore into the vicinity of the
      mRNA target (antisense and RNA interference technology) or DNA target (gene
      therapy). Since these drugs are intended for systemic administration in most
      cases, the term 'delivery' should be expanded to include pharmacokinetics as
      woell. However, most studies of nonradioactive drugs emphasize pharmacology and
      efficacy at the expense of pharmacokinetics. Fortunately, by tracing
      radioactivity in the living subject, the development of radiopharmaceuticals for
      nuclear imaging is providing valuable data on pharmacokinetics as well as cell
      membrane transport of a limited, but important number of oligomers, primarily in
      connection with antisense therapy and pretargeting of tumors. This review is
      concerned with the influence of chemical structure on the delivery properties of
      radiolabeled oligomers primarily for nuclear imaging studies and largely in mouse
      models of tumors.

PMID- 16610767
TI  - ENA oligonucleotides as therapeutics.
AB  - Oligonucleotides containing 2'-O,4'-C-ethylene-bridged nucleic acid (ENA)
      residues have two notable properties: (i) considerable affinity to complementary
      single-stranded RNA and double-stranded DNA; and (ii) dramatically high
      resistance against nucleases. On the basis of these properties, the in vitro and
      in vivo applications of ENA for gene silencing as antisense oligonucleotides,
      triplex-forming oligonucleotides and small interfering RNAs are discussed here.
      ENA oligonucleotides also have potential as therapeutic agents for Duchenne
      muscular dystrophy by a mechanism of exon skipping.

PMID- 16610768
TI  - HBV-ISS (Dynavax).
AB  - Dynavax is developing HBV-ISS (Heplisav), a vaccine based on hepatitis B virus
      (HB V) antigens and Dynavax' s immunostimulatory DNA sequence (ISS) ISS-1018, an
      adjuvant that acts as a TLR-9 agonist, for the potential prevention and treatment
      of HBV infection.

PMID- 16610769
TI  - HuCNS-SC (StemCells).
AB  - HuCNS-SC, a proprietary human neural stem cells product, is being developed as a
      cellular therapy for the potential treatment of Batten disease, one of a group of
      disorders known as neural ceroid lipofuscinoses (NCL). Developer StemCells is
      also investigating the therapy for spinal cord injury and other central nervous
      system disorders, such as demyelinating disease, stroke and Alzheimer's disease.
      A phase I trial of HuCNS-SC for infantile and late-infantile NCL has been
      initiated, following the March 2006 U.S. Food and Drug Administration approval of
      StemCells' investigational new drug application.

PMID- 16610770
TI  - SGN-30 (Seattle genetics).
AB  - Seattle Genetics is developing SGN-30, an intravenously administered recombinant
      anti-CD30 monoclonal antibody for the potential treatment of Hodgkin's disease,
      certain non-Hodgkin's lymphomas, specific leukemia, and immunological diseases
      such as multiple sclerosis and systemic lupus erythematosus. Phase II trials in
      patients with Hodgkin's disease, anaplastic large cell lymphoma, and cutaneous
      lymphoma have been conducted in the U.S. and Europe.

PMID- 16610771
TI  - Moving onward and upward.

PMID- 16610772
TI  - Society of Trauma Nurses position statement on screening for alcohol use in adult
      primary care.

PMID- 16610773
TI  - Family perception: quality of life following a child's traumatic injury.
AB  - This prospective research study evaluated the parent's perception of their
      child's quality of life at 1 and 6 months following injury, using the Child
      Health Questionnaire to measure outcomes. At both 1 and 6 months postinjury, the
      physical summary and psychosocial summary scores were significantly lower than US
      norms for all levels of injury severity. Predictors of lower physical and
      psychosocial scores, such as the Injury Severity Score and specific location of
      injury, were determined. This study demonstrates the long-term impact of injury
      and validates the need for earlier intervention and anticipatory guidance for the
      child and family.

PMID- 16610774
TI  - Early recognition and treatment of shock in the pediatric patient.
AB  - Pediatric cardiopulmonary arrest is frequently a terminal event of an
      unrecognized progressive shock state. This article describes predisposing factors
      and classifications of shock as they relate to pediatric patients. It assists the
      experienced pediatric nurse as well as the nurse who is less experienced in
      caring for children in identifying early shock in this population and provides
      practical advice on the assessment of children. In addition, management and
      intervention techniques are addressed.

PMID- 16610775
TI  - Obesity and the trauma patient: challenges and guidelines for care.
AB  - Optimal care of the morbidly obese trauma patient involves a team approach that
      will combine appropriate diagnosis and therapeutic interventions for critically
      injured patients who are weight challenged. The incidence of obese patients and
      injury is far too common in trauma centers across our country. Establishment of
      local procedures and guidelines to facilitate management of obese patients is
      crucial to minimizing the risks for morbidity and mortality, and ultimately,
      improving their outcomes.

PMID- 16610776
TI  - A comparative approach to deep vein thrombosis risk assessment.
AB  - Trauma patients are at risk for developing DVT/PE. The Bronson Trauma Model
      incorporates a DVT scoring system into the daily routine for all injured patients
      admitted to the Trauma Care Unit. Dr Paul Blostein added the DVT Risk Assessment
      spreadsheet to his personal digital assistant and made it available to other
      members of the team to allow calculation of a patient's DVT risk percentage
      during daily multidisciplinary rounds in the Trauma Care Unit. The Trauma Program
      has found the incorporation of the scoring systems into the trauma registry to be
      a value-added component of our performance improvement process. Bronson's unique
      model of trauma care, where patients are admitted and discharged from the same
      room, combined with today's technology of wireless laptops and personal digital
      assistants, promotes a progressive approach to DVT/PE prophylaxis and performance
      improvement. Our trauma follow-up program has proven to be effective in
      reintegrating patients back into the trauma system to optimize their functional
      status and improve their outcome.

PMID- 16610777
TI  - Trauma care: an exceptional delivery system.
AB  - Systems of trauma care within an institution can vary based on a variety of
      factors such as patient volume, university affiliation, level of trauma center,
      and available resources. The trauma care delivery system at Cooper University
      Hospital allows for a collaborative model that provides a continuum of patient
      care. High level resuscitations are performed in a dedicated area by a dedicated
      team supporting efficiency and competency.

PMID- 16610778
TI  - The leader within.

PMID- 16610779
TI  - Identification of ellagic acid as potent inhibitor of protein kinase CK2: a
      successful example of a virtual screening application.
AB  - Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein
      kinase whose abnormally high constitutive activity is suspected to underlie its
      pathogenic potential in neoplasia and other diseases. Using a virtual screening
      approach, we have identified the ellagic acid, a naturally occurring tannic acid
      derivative, as a novel potent CK2 inhibitor. At present, ellagic acid represents
      the most potent known CK2 inhibitor (K(i) = 20 nM).

PMID- 16610780
TI  - Biosensor-based kinetic characterization of the interaction between HIV-1 reverse
      transcriptase and non-nucleoside inhibitors.
AB  - Details of the interaction between HIV-1 reverse transcriptase and non-nucleoside
      inhibitors (NNRTIs) have been elucidated using a biosensor-based approach. This
      initial study was performed with HIV-1 reverse transcriptase mutant K103N, the
      phenethylthioazolylthiourea compound (PETT) MIV-150, and the three NNRTIs
      licensed for clinical use: nevirapine, delavirdine, and efavirenz. Mathematical
      evaluation of the experimental data with several interaction models revealed that
      the four inhibitors interacted with HIV-1 RT with varying degrees of complexity.
      The simplest adequate model accounted for two different conformations of the free
      enzyme, of which only one can bind the inhibitor, consistent with a previously
      hypothesized population-shift model including a preformation of the NNRTI binding
      site. In addition, a heterogeneous binding was observed for delavirdine,
      efavirenz, and MIV-150, indicating that two noncompetitive and kinetically
      distinct enzyme-inhibitor complexes could be formed. Furthermore, for these
      compounds, there were indications for ligand-induced conformational changes.

PMID- 16610781
TI  - Interaction kinetic characterization of HIV-1 reverse transcriptase non
      nucleoside inhibitor resistance.
AB  - To decipher the mechanism for non-nucleoside inhibitor resistance of HIV-1
      reverse transcriptase, the kinetics of the interaction between wild type and drug
      resistant variants of the enzyme and structurally diverse inhibitors were
      determined. Substitution of amino acid residues in the inhibitor binding site
      resulted in altered rate constants for the pre-equilibrium between two unliganded
      forms of the enzyme, and for the association and dissociation of the inhibitor
      enzyme interaction. The Y181C, V108I, and P225H substitutions affected primarily
      the association and dissociation rate constants, while the K103N and the L100I
      substitutions also influenced the equilibrium between the two forms of the free
      enzyme. The K103N and the L100I substitutions were found to facilitate both the
      entry of the inhibitor into the binding pocket as well as its exit, in contrast
      to what has been reported elsewhere. Interaction kinetic-based resistance
      profiles showed that phenethylthiazolylthiourea compounds were relatively
      insensitive to the studied substitutions.

PMID- 16610782
TI  - Slow-binding human serine racemase inhibitors from high-throughput screening of
      combinatorial libraries.
AB  - One-bead one-compound combinatorial chemistry together with a high-throughput
      screen based on fluorescently labeled enzyme allowed the identification of slow
      binding inhibitors of human serine racemase (hSR). A peptide library of
      topographically segregated encoded resin beads was synthesized, and several hSR
      binding compounds were isolated, identified, and resynthesized for further
      kinetic study. Of these, several showed inhibitory effects with moderate potency
      (high micromolar K(I)s) toward hSR. A clear structural motif was identified
      consisting of 3-phenylpropionic acid and histidine moieties. Importantly, the
      inhibitors identified showed no structural similarities to the natural substrate,
      L-serine. Detailed kinetic analyses of the properties of selected inhibitors show
      that the screening protocol used here selectively identifies slow binding
      inhibitors. They provide a pharmacophore for the future isolation of more potent
      ligands that may prove useful in probing and understanding the biological role of
      hSR.

PMID- 16610783
TI  - Practical synthesis and evaluation of the biological activities of 1alpha,25
      dihydroxyvitamin D3 antagonists, 1alpha,25-dihydroxyvitamin D3-26,23-lactams.
      Designed on the basis of the helix 12-folding inhibition hypothesis.
AB  - A practical synthetic route to novel vitamin D antagonists of DLAM (1alpha,25
      dihydroxyvitamin D(3)-26,23-lactam) was developed from vitamin D(2) via the 1,3
      dipolar cycloaddition reaction as a key step. Six DLAM derivatives (24 compounds)
      with a variety of nitrogen substituents and stereochemistries at C23 and C25 were
      synthesized. Among these new derivatives, (23S,25S)-DLAM isomers bound
      effectively to VDRs and showed antagonistic activity in the HL-60 cell
      differentiation inhibition assay. The importance of the substituent on the
      nitrogen of DLAMs for antagonistic activity was also suggested by computational
      docking studies.

PMID- 16610784
TI  - Modeling the preferred shapes of polyamine transporter ligands and
      dihydromotuporamine-C mimics: shovel versus hoe.
AB  - Preferred conformers generated from motuporamine and anthracene-polyamine
      derivatives provided insight into the shapes associated with polyamine
      transporter (PAT) recognition and potentially dihydromotuporamine C (4a)
      bioactivity. Molecular modeling revealed that N(1)-(anthracen-9-ylmethyl)-3,3
      triamine (6a), N(1)-(anthracen-9-ylmethyl)-4,4-triamine (6b), N(1)-(anthracen-9
      ylmethyl)-N(1)-ethyl-3,3-triamine (7a), N(1)-(anthracen-9-ylmethyl)-N(1)-ethyl
      4,4-triamine (7b), and 4a all preferred a hoe motif. This hoe shape was defined
      by the all-anti polyamine shaft extending above the relatively flat, appended
      ring system. The hoe geometry was also inferred by the (1)H NMR spectrum of the
      free amine of 7a (CDCl(3)), which showed a strong shielding effect of the
      anthracene ring on the chemical shifts associated with the appended polyamine
      chain. This shielding effect was found to be independent over a broad
      concentration range of 7a, which also supported an intramolecular phenomenon. The
      degree of substitution at the N(1)-position seems to be an important determinant
      of both the molecular shape preferences and biological activity of
      anthracenylmethyl-polyamine conjugates.

PMID- 16610785
TI  - Catalytic site prediction and virtual screening of cytochrome P450 2D6 substrates
      by consideration of water and rescoring in automated docking.
AB  - Automated docking strategies successfully applied to binding mode predictions of
      ligands in Cyt P450 crystal structures in an earlier study (de Graaf et al. J.
      Med. Chem. 2005, 7, 2308-2318) were used for the catalytic site prediction (CSP)
      of 65 substrates in a CYP2D6 homology model. The consideration of water molecules
      at predicted positions in the active site and the rescoring of pooled docking
      poses from four different docking programs (AutoDock, FlexX, GOLD-Goldscore, and
      GOLD-Chemscore) with the SCORE scoring function enabled the successful prediction
      of experimentally reported sites of catalysis of more than 80% of the substrates.
      Three docking algorithms (FlexX, GOLD-Goldscore, and GOLD-Chemscore) were
      subsequently used in combination with six scoring functions (Chemscore, DOCK,
      FlexX, GOLD, PMF, and SCORE) to assess the ability of docking-based virtual
      screening methods to prioritize known CYP2D6 substrates seeded into a drug-like
      chemical database (in the absence and presence of active-site water molecules).
      Finally, the optimal docking strategy in terms of virtual screening accuracy,
      GOLD-Chemscore with the consideration of active-site water (60% of known
      substrates recovered in the top 5% of the ranked drug-like database), was
      verified experimentally; it was successfully used to identify high-affinity
      CYP2D6 ligands among a larger proprietary database.

PMID- 16610786
TI  - Probing the structure-function relationship of polyene macrolides: engineered
      biosynthesis of soluble nystatin analogues.
AB  - Although polyene macrolides are efficient antifungal agents with fungicidal mode
      of action, their use in medical practice is problematic due to their low
      solubility and significant human toxicity. In an attempt to address the
      solubility problem, we have obtained two analogues of nystatin with hydroxy
      groups at positions C31 and C33 through manipulation of the nystatin polyketide
      synthase in the producing organism Streptomyces noursei. Structures of the
      analogues were confirmed by nuclear magnetic resonance (NMR), and their
      solubility was found to be more than 2000 times higher than that of nystatin.
      However, both analogues were shown to have lost antifungal activity, implying
      that the integrity of the hydrophobic polyene region of the nystatin molecule is
      crucial for the fungicidal action. NMR data and computer modeling performed for
      the new analogues suggested conformational changes together with a significantly
      increased structural disorder, which may account for both increased solubility
      and the loss of activity.

PMID- 16610787
TI  - Synthesis and characterization of 3-arylquinazolinone and 3-arylquinazolinethione
      derivatives as selective estrogen receptor beta modulators.
AB  - On the basis of the stucture of genistein, a new series of 3-arylquinazolines was
      prepared and tested for their estrogen receptor (ER) alpha and beta affinities.
      5,7-Dihydroxy-3-(4-hydroxyphenyl)-4(3H)-quinazolinone (1aa) acts as an agonist on
      both ER subtypes. It has 62-fold higher binding affinity [IC(50)(ERbeta) = 179
      nM] and 38-fold higher functional potency in a transcription assay
      [EC(50)(ERbeta) = 76 nM] with ERbeta than with ERalpha, thus improving upon the
      selectivity of genistein. All of the analogues showed preferential binding
      affinity for ERbeta. Many are also more potent in activating transcription by
      ERbeta than by ERalpha. Transformation of the C=O functionality at position 4
      into a C=S group provided 5,7-dihydroxy-3-(4-hydroxyphenyl)-4(3H)
      quinazolinethione (1ba), which acts as an agonist on both ER subtypes but has 56
      fold higher binding affinity for ERbeta over ERalpha [IC(50)(ERbeta) = 47 nM] and
      215-fold higher potency in the transcription assay [EC(50)(ERbeta) = 13 nM].
      These ERbeta-selective compounds may represent valuable tools in understanding
      the differences in structure and biological function of ERbeta and ERalpha.

PMID- 16610788
TI  - Anthranilic acid based CCK1 receptor antagonists and CCK-8 have a common step in
      their "receptor desmodynamic processes".
AB  - The interaction between the 1-47 N-terminus of the CCK(1)-R and the anthranilic
      acid based antagonists has been investigated by fluorescence spectroscopy. These
      antagonists interact with W39 of the N-terminal domain of the CCK(1)-R like that
      of the endogenous ligand CCK-8. This specific interaction was not found in other
      nonpeptide ligands of the CCK(1)-R. Conformational studies, using NMR and energy
      minimization procedures, have allowed formulation of a new hypothesis on the
      CCK(1)-R binding mode of the anthranilic antagonists.

PMID- 16610789
TI  - Molecular docking-based study of vasopressin analogues modified at positions 2
      and 3 with N-methylphenylalanine: influence on receptor-bound conformations and
      interactions with vasopressin and oxytocin receptors.
AB  - In this study, four cyclic vasopressin (CYFQNCPRG-NH(2), AVP) analogues
      substituted at positions 2 and 3 with four combinations of enantiomers of N
      methylphenylalanine have been investigated. Three-dimensional structures of
      analogues have been formerly determined using NMR spectroscopy in dimethyl
      sulfoxide. Three-dimensional models of the vasopressin and oxytocin receptors
      were constructed by combining the multiple sequence alignment and the RD crystal
      structure as a template. The analogues have been docked into the receptor using
      the AutoDock program. The relaxation of the receptor-ligand complexes using
      energy minimization, followed by the constrained simulated annealing protocols
      (CSA), has been performed. The receptor-bound conformations of the investigated
      analogues have been proposed. We concluded that the N-methylated residues at
      positions 2 and 3 act as a structural restraint, determining the conformation of
      analogues, their location inside the receptor cavity, and mutual arrangement of
      the aromatic side chains. The conserved polar residues constitute the handles
      keeping the biologically active analogues inside the binding cavity. The Arg(8)
      D(2.65) salt bridge might be responsible for analogue-selective binding in OTR
      and V1aR versus V2R, where the positively charged K(2.65) 100 is present at the
      equivalent position.

PMID- 16610790
TI  - Optimal charges in lead progression: a structure-based neuraminidase case study.
AB  - Collective experience in structure-based lead progression has found electrostatic
      interactions to be more difficult to optimize than shape-based ones. A major
      reason for this is that the net electrostatic contribution observed includes a
      significant nonintuitive desolvation component in addition to the more intuitive
      intermolecular interaction component. To investigate whether knowledge of the
      ligand optimal charge distribution can facilitate more intuitive design of
      electrostatic interactions, we took a series of small-molecule influenza
      neuraminidase inhibitors with known protein cocrystal structures and calculated
      the difference between the optimal and actual charge distributions. This
      difference from the electrostatic optimum correlates with the calculated
      electrostatic contribution to binding (r(2) = 0.94) despite small changes in
      binding modes caused by chemical substitutions, suggesting that the optimal
      charge distribution is a useful design goal. Furthermore, detailed suggestions
      for chemical modification generated by this approach are in many cases consistent
      with observed improvements in binding affinity, and the method appears to be
      useful despite discrete chemical constraints. Taken together, these results
      suggest that charge optimization is useful in facilitating generation of compound
      ideas in lead optimization. Our results also provide insight into design of
      neuraminidase inhibitors.

PMID- 16610791
TI  - The T-Taxol conformation.
AB  - T-Taxol is a proposal for the bioactive conformation of paclitaxel (PTX) derived
      from fitting ligand conformations to the electron crystallographic (EC) density.
      Although confirmed by a number of studies, some structural ambiguities based on
      the interpretation of two solid-state REDOR (13)C-(19)F distances in a
      fluorinated PTX derivative remain. An evaluation of the static and dynamic
      properties of the PTX-tubulin complex shows that small 6-12 degrees variations in
      calculated torsions and a justifiable increase of the REDOR distance error to >
      or = +/-0.7 A readily resolves key discrepancies around T-Taxol's service as the
      bioactive conformation. In addition, conformational analysis reveals a range of
      (13)C-(19)F separations compatible with the REDOR measurements suggesting that
      the present PTX REDOR distances may not provide a precise model for bioactive,
      tubulin-bound bridged taxanes. In addition, we show that New York-Taxol (PTX-NY),
      a recently proposed alternative to T-Taxol, is incompatible with both the EC
      density and the activity of a highly active series of bridged taxanes.

PMID- 16610792
TI  - Refinement of the benzodiazepine receptor site topology by structure-activity
      relationships of new N-(heteroarylmethyl)indol-3-ylglyoxylamides.
AB  - N-(heteroarylmethyl)indol-3-ylglyoxylamides (1-26) were synthesized and evaluated
      as ligands of the benzodiazepine receptor (BzR) to probe the hydrogen bonding
      properties of the so-called S(1) site of the BzR by means of suitable
      heterocyclic side chains. SARs were developed in light of our hypothesis of
      binding modes A and B. Pyrrole and furan derivatives adopting mode A (2, 8, 10,
      20, 22) turned out to be more potent (K(i) values < 35 nM) than their analogues
      lacking hydrogen bonding heterocyclic side chains. These data suggest that the
      most potent indoles interact with a hydrogen bond acceptor/donor (HBA/D) group
      located within the S(1) site of the BzR. Compounds 1, 2, 8, 19, 20, and 22,
      tested at recombinant rat alpha(1)beta(2)gamma(2), alpha(2)beta(2)gamma(2), and
      alpha(5)beta(3)gamma(2) BzRs, elicited selectivity for the
      alpha(1)beta(2)gamma(2) isoform. On the basis of published mutagenesis studies
      and the present SARs, we speculate that the S(1) HBA/D group might be identified
      as the hydroxyl of alpha(1)-Tyr209 or of other neighboring amino acids.

PMID- 16610794
TI  - Structure-based optimization of azole antifungal agents by CoMFA, CoMSIA, and
      molecular docking.
AB  - In a continuing effort to develop highly potent azole antifungal agents, the
      three-dimensional quantitative structure-activity relationship methods, CoMFA and
      CoMSIA, were applied using a set of novel azole antifungal compounds. The binding
      mode of the compounds at the active site of lanosterol 14alpha-demethylase was
      further explored using the flexible docking method. Various hydrophobic, van der
      Waals, pi-pi stacking, and hydrogen bonding interactions were observed between
      the azoles and the enzyme. Based on results from the molecular modeling, a
      receptor-based pharmacophore model was established to guide the rational
      optimization of the azole antifungal agents. Thus, a total of 57 novel azoles
      were designed and synthesized by a three-step optimization process. In vitro
      antifungal assay revealed that the antifungal activities of these novel azoles
      were greatly improved, which confirmed the reliability of the model from
      molecular modeling.

PMID- 16610793
TI  - Fluorine-substituted cyclofenil derivatives as estrogen receptor ligands:
      synthesis and structure-affinity relationship study of potential positron
      emission tomography agents for imaging estrogen receptors in breast cancer.
AB  - In a search for estrogen receptor (ER) ligands to be radiolabeled with fluorine
      18 for imaging of ER-positive breast tumors with positron emission tomography
      (PET), we investigated cyclofenil analogues substituted at the C3 or C4 position
      of the cyclohexyl group. McMurry coupling of 4,4'-dihydroxybenzophenone with
      various ketones produced key cyclofenil intermediates, from which C3 and C4
      substituents containing alkyl and various oxygen or fluorine-substituted alkyl
      groups were elaborated. Binding assays to both ERalpha and ERbeta revealed that
      the C3 site is more tolerant of steric bulk and polar groups than the C4 site,
      consistent with a computational model of the ERalpha ligand binding pocket.
      Fluorine substitution is tolerated very well at some sites, giving some compounds
      having affinities comparable to or higher than that of estradiol. These fluoro
      and fluoroalkyl cyclofenils merit further consideration as fluorine-18 labeled ER
      ligands for PET imaging of ERs in breast tumors.

PMID- 16610795
TI  - 4-quinolone derivatives: high-affinity ligands at the benzodiazepine site of
      brain GABA A receptors. synthesis, pharmacology, and pharmacophore modeling.
AB  - The 3-ethoxycarbonyl-4-quinolone compound 1 has previously been identified via a
      database search as an interesting lead compound for ligand binding at the
      benzodiazepine site of GABA(A) receptors (Kahnberg et al. J. Mol. Graphics
      Modelling 2004, 23, 253-261). Pharmacophore-guided optimization of this lead
      compound yielded a number of high-affinity ligands for the benzodiazepine site
      including compounds 20 and 23-25 displaying sub-nanomolar affinities. A few of
      the compounds have been tested on the alpha(1)beta(2)gamma(2S) and
      alpha(3)beta(2)gamma(2S) GABA(A) receptor subtypes, and two of the compounds (5
      and 19) display selectivity for alpha(1)- versus alpha(3)-containing receptors by
      a factor of 22 and 27, respectively. This selectivity for
      alpha(1)beta(2)gamma(2S) is in the same range as that for the well-known alpha(1)
      subunit selective compound zolpidem.

PMID- 16610796
TI  - Evaluation of basic amphipathic peptides for cellular delivery of antisense
      peptide nucleic acids.
AB  - Cellular permeation peptides have been used successfully for the delivery of a
      variety of cargoes across cellular membranes, including large hydrophilic
      biomolecules such as proteins, oligonucleotides, or plasmid DNA. For the present
      work, a series of short amphipathic peptides was designed to elucidate the
      structural requirements for efficient and nontoxic delivery of peptide nucleic
      acids (PNAs). On the basis of an idealized alpha-helical structure, the helical
      parameters were modulated systematically to yield peptides within a certain range
      of hydrophobicity and amphipathicity. The corresponding PNA conjugates were
      synthesized and characterized in terms of secondary structure, enzymatic
      stability, and antisense activity. The study revealed correlations between the
      physicochemical and biophysical properties of the conjugates and their biological
      activity and led to the development of potent peptide vectors for the cellular
      delivery of antisense PNAs. Two representative compounds were radiolabeled and
      evaluated for their biodistribution in healthy mice.

PMID- 16610797
TI  - Free radical scavenging and antioxidant activities of substituted
      hexahydropyridoindoles. Quantitative structure-activity relationships.
AB  - New synthetic substituted hexahydropyridoindoles were studied for their radical
      scavenging ability in a system of an ethanolic solution of alpha,alpha'-diphenyl
      beta-picrylhydrazyl and for their lipid peroxidation inhibitory properties in a
      suspension of unilamellar dioleoylphosphatidylcholine liposomes. The activities
      in both in vitro systems were correlated with several structural parameters. In
      the homogeneous system of alpha,alpha'-diphenyl-beta-picrylhydrazyl, the sum of
      aromatic substitution constants (sigma(+)) and the hydration energy were shown to
      be effective predictors of the radical scavenging activity of the
      hexahydropyridoindole derivatives. Moreover, in the heterogeneous system
      comprising a model liposomal membrane, the overall antioxidant activity of the
      compounds was affected by their lipid-phase availability governed by the
      lipophilicity and basicity of the molecules.

PMID- 16610798
TI  - A chemical switch for the modulation of the functional activity of higher
      homologues of histamine on the human histamine H3 receptor: effect of various
      substitutions at the primary amino function.
AB  - In an effort to establish the structural requirements for agonism, neutral
      antagonism, and inverse agonism at the human histamine H(3) receptor (H(3)R) we
      have prepared a series of higher homologues of histamine in which the terminal
      nitrogen of the side chain has been either mono- or disubstituted with several
      aliphatic, alicyclic, and aromatic moieties or incorporated in cyclic systems.
      The novel ligands have been pharmacologically investigated in vitro for their
      affinities on the human H(3)R and H(4)R subtypes by radioligand displacement
      experiments and for their intrinsic H(3)R activities via a CRE-mediated beta
      galactosidase reporter gene assay. Subtle changes of the substitution pattern at
      the side chain nitrogen alter enormously the pharmacological activity of the
      ligands, resulting in a series of compounds with a wide spectrum of
      pharmacological activities. Among the several neutral H(3)R antagonists
      identified within this series, compounds 2b and 2h display an H(3)R affinity in
      the low nanomolar concentration range (pK(i) values of 8.1 and 8.4,
      respectively). A very potent and selective H(3)R agonist (1l, pEC(50) = 8.9,
      alpha = 0.94) and a very potent, though not highly selective, H(3)R inverse
      agonist (2k, pIC(50) = 8.9, alpha = -0.97) have been identified as well.

PMID- 16610799
TI  - Photodynamic efficiency of diethylene glycol-linked glycoconjugated porphyrins in
      human retinoblastoma cells.
AB  - Photodynamic therapy (PDT) is emerging as a new strategy for the conservative
      treatment of hereditary retinoblastoma. The glycoconjugated porphyrins TPP(p-Deg
      O-alpha-GalOH)(3), TPP(p-Deg-O-beta-GalOH)(3), TPP(p-Deg-O-alpha-ManOH)(3), and
      their S-analogues were synthesized to obtain efficient photosensitizers with some
      retinoblastoma cell affinity. In these systems, a sugar motif and porphyrin core
      were linked by a diethylene glycol spacer (Deg). Cellular uptake, localization,
      and photoactivity have been examined in human retinoblastoma cells (Y79). After
      preincubation with corresponding glycosylated albumin, the uptake of TPP(p-Deg-O
      beta-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) was 40-45% inhibited, indicating a
      possible cell-sugar-receptor saturation. High photoactivity was observed for the
      two alpha-galacto/manno porphyrins 8 and 10 (LD(50) = 0.05 and 0.35 muM,
      respectively) at 514 nm and low fluence (1 J/cm(2)). Analysis by MALDI-TOF mass
      spectrometry only indicated a small metabolic cleavage of the O-glycoconjugates
      and a good stability of the S-glycoside porphyrins. On the basis of these in
      vitro data, TPP(p-Deg-O-alpha-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) were
      selected for in vivo studies.

PMID- 16610800
TI  - 2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor
      antagonists.
AB  - Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth
      hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been
      shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin
      actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense
      oligonucleosides resulted in weight loss and food intake decrease in rodents.
      Here we report the effects of GHS-R antagonists, some of which were potent,
      selective, and orally bioavailable. A structure-activity relationship study led
      to the discovery of 8a, which was effective in decreasing food intake and body
      weight in several acute rat studies.

PMID- 16610801
TI  - Structure-activity relationship studies on N3-substituted willardiine derivatives
      acting as AMPA or kainate receptor antagonists.
AB  - N3-substitution of the uracil ring of willardiine with a variety of carboxyalkyl
      or carboxybenzyl substituents produces AMPA and kainate receptor antagonists. In
      an attempt to improve the potency and selectivity of these AMPA and kainate
      receptor antagonists a series of analogues with different terminal acidic groups
      and interacidic group spacers was synthesized and pharmacologically
      characterized. (S)-1-(2-Amino-2-carboxyethyl)-3-(2-carboxythiophene-3
      ylmethyl)pyrimidine-2,4-dione (43, UBP304) demonstrated high potency and
      selectivity toward native GLU(K5)-containing kainate receptors (K(D) 0.105 +/-
      0.007 microM vs kainate on native GLU(K5); K(D) 71.4 +/- 8.3 microM vs (S)-5
      fluorowillardiine on native AMPA receptors). On recombinant human GLU(K5),
      GLU(K5)/GLU(K6), and GLU(K5)/GLU(K2), K(B) values of 0.12 +/- 0.03, 0.12 +/-
      0.01, and 0.18 +/- 0.02 microM, respectively, were obtained for 43. However, 43
      displayed no activity on homomeric GLU(K6) or GLU(K7) kainate receptors or
      homomeric GLU(A1-4) AMPA receptors (IC(50) values > 100 microM). Thus, 43 is a
      potent and selective GLU(K5) receptor antagonist.

PMID- 16610802
TI  - Investigating the role of stereochemistry in the activity of anticancer
      acylfulvenes: synthesis, reductase-mediated bioactivation, and cellular toxicity.
AB  - Acylfulvenes comprise a family of semisynthetic natural product derivatives with
      potent antitumor activities. Previous studies indicated that acylfulvenes are
      bioactivated by NADPH-dependent alkenal/one reductase (AOR), presumably
      generating intermediates with the capacity to alkylate cellular targets, such as
      DNA, proteins, and glutathione. This process is thought to induce apoptosis, and
      the chemical and biochemical pathways involved are topics of current
      investigation. In this study, four acylfulvene analogues were synthesized: (-)
      acylfulvene, (+)-acylfulvene, (-)-(hydroxymethyl)acylfulvene, and (+)
      (hydroxymethyl)acylfulvene. These compounds were synthesized by a chiral
      resolution method, described for the first time in this report, and by asymmetric
      synthesis using a method formally demonstrated previously. Cell toxicity studies
      indicate a positive correlation between AOR level and acylfulvene sensitivity.
      The absolute configuration of acylfulvene analogues has a significant influence
      on cytotoxicity. (-)-(Hydroxymethyl)acylfulvene is 25 times more potent than (+)
      (hydroxymethyl)acylfulvene in cells transfected with an AOR overexpression
      vector. Based on kinetic parameters, the rates of AOR-mediated activation are
      more strongly dependent on acylfulvene substitution than on absolute
      stereochemistry. These data support the role of AOR-mediated metabolism and
      indicate the involvement of other stereochemically dictated pathways, such as
      transport and biomolecule binding, in contributing to the cytotoxicity of
      acylfulvenes.

PMID- 16610803
TI  - A pyridazine series of alpha2/alpha3 subtype selective GABA A agonists for the
      treatment of anxiety.
AB  - The development of a series of GABA(A) alpha2/alpha3 subtype selective pyridazine
      based benzodiazepine site agonists as anxiolytic agents with reduced
      sedative/ataxic potential is described, including the discovery of 16, a
      remarkably alpha3-selective compound ideal for in vivo study. These ligands are
      antagonists at the alpha1 subtype, with good CNS penetration and receptor
      occupancy, and excellent oral bioavailability.

PMID- 16610804
TI  - Design and synthesis of 1-indol-1-yl-propan-2-ones as inhibitors of human
      cytosolic phospholipase A2alpha.
AB  - The synthesis and structure-activity relationship study of a series of 1-indol-1
      yl-3-phenoxypropan-2-one inhibitors of cytosolic phospholipase A(2)alpha
      (cPLA(2)alpha) are described. The compounds were evaluated in a vesicle assay
      with isolated cPLA(2)alpha and in cellular assays with intact human platelets.
      Systematic variation led to 3-methylhydrogen 1-[3-(4-decyloxyphenoxy)-2
      oxopropyl]indole-3,5-dicarboxylate (57), which revealed the highest activity
      against the isolated enzyme. With an IC(50) value of 4.3 nM in this assay, it is
      one of the most potent in vitro cPLA(2)alpha inhibitors known today.

PMID- 16610805
TI  - Synthesis and anti-BVDV activity of acridones as new potential antiviral agents.
AB  - In this study we report the design, synthesis, and activity against bovine viral
      diarrhea virus (BVDV) of a novel series of acridone derivatives. BVDV is
      responsible for major losses in cattle. The virus is also considered to be a
      valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies.
      Some of the synthesized acridones elicited selective anti-BVDV activity with
      EC(50) values ranging from 0.4 to 4 microg/mL and were not cytotoxic at
      concentrations that were 25- to 200-fold higher (CC(50) >100 microg/mL). It was
      proven that the most potent acridone derivative 10 was able to not only protect
      cells from virus-induced cytopathic effect but also reduce the production of
      infectious virus and extracellular viral RNA. Furthermore, compound 10, as well
      as a number of other analogues, inhibited HCV replication to some extent.
      However, there was no direct correlation between anti-BVDV and anti-HCV activity.
      Thus, the acridone scaffold, when appropriately functionalized, can yield
      compounds with selective activity against pestiviruses and related viruses such
      as the HCV.

PMID- 16610806
TI  - New NO-releasing pharmacodynamic hybrids of losartan and its active metabolite:
      design, synthesis, and biopharmacological properties.
AB  - In a preliminary work, we reported two NO-sartans, possessing the characteristics
      of an AT(1) antagonist and a "slow NO donor", obtained by adding NO-donor side
      chains to losartan 1. The NO release from an NO-sartan should be modulated in
      order to strengthen the antihypertensive activity of the native drug and to
      ensure additional effects, such as the antiplatelet and anti-ischemic ones. To
      obtain a collection of prototypical NO-sartans, showing different rates of NO
      release, new NO-donor moieties have been linked to 1 or its active metabolite 2
      (EXP 3174). Almost all the synthesized compounds exhibited both AT(1)-antagonist
      and NO-mediated vasorelaxing properties, with a wide range of NO-releasing rates.
      Further pharmacological investigation on compound 4a showed that it possessed
      antihypertensive and cardiac antihypertrophic effects similar to those of the
      reference AT(1)-blocking or ACE-inhibiting drugs. Furthermore, the additional
      anti-ischemic cardio-protective properties and antiplatelet effects of 4a have
      been preliminarily investigated.

PMID- 16610807
TI  - Structural characterization, DNA interactions, and cytotoxicity of new
      transplatin analogues containing one aliphatic and one planar heterocyclic amine
      ligand.
AB  - We report in the present work new analogues of clinically ineffective transplatin
      in which one ammine group was replaced by aliphatic and the other by a planar
      heterocyclic ligand, namely trans-[PtCl(2)(isopropylamine)(3-(hydroxymethyl)
      pyridine)], 1, and trans-[PtCl(2)(isopropylamine)(4-(hydroxymethyl)-pyridine)],
      2. The new compounds, in comparison with parent transplatin, exhibit radically
      enhanced activity in tumor cell lines both sensitive and in particular resistant
      to cisplatin. Concomitantly, the DNA binding mode of 1 and 2 compared to parent
      transplatin and other antitumor analogues of transplatin in which only one ammine
      group was replaced is also different. The results also suggest that the reactions
      of glutathione and metallothionein-2 with compounds 1 and 2 do not play a crucial
      role in their overall biological effects. In addition, the monofunctional adducts
      of 1 and 2 are quenched by glutathione considerably less than the adducts of
      transplatin, which may potentiate cytotoxic effects of these new platinum
      complexes.

PMID- 16610808
TI  - Amino functionalized novel cholic acid derivatives induce HIV-1 replication and
      syncytia formation in T cells.
AB  - Synthesis of C-11 azido/amino functionalized cholic acid derivatives has been
      achieved in excellent yields. Contrary to the previous prediction of analogous
      compounds to be HIV-1 protease inhibitors, in the present study these novel
      cholic acid derivatives induced host cell fusion during the progress of HIV-1
      infection and produced multinucleated giant cells. This is the first report of
      syncytia induction and enhancement of viral replication in HIV-1 infected T cells
      by cholic acid derivatives.

PMID- 16610809
TI  - Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as
      potent Plasmodium falciparum growth inhibitors.
AB  - A series of fosmidomycin analogues featuring restricted conformational mobility
      has been synthesized and evaluated as inhibitors of 1-deoxy-D-xylulose 5
      phosphate (DOXP) reductoisomerase and as growth inhibitors of P. falciparum. The
      enantiomerically pure trans-cyclopropyl N-acetyl analogue 3b showed comparable
      inhibitory activity as fosmidomycin toward E. coli DOXP reductoisomerase and
      proved equally active when tested in vitro for P. falciparum growth inhibition.
      Conversely, the alpha-phenyl cis-cyclopropyl analogue 4 showed virtually no
      inhibition of the enzyme.

PMID- 16610810
TI  - Neuropeptide Y (NPY) Y4 receptor selective agonists based on NPY(32-36):
      development of an anorectic Y4 receptor selective agonist with picomolar
      affinity.
AB  - We have previously shown [Cys-Trp-Arg-Nva-Arg-Tyr-NH(2)](2), 1, to be a
      moderately selective neuropeptide Y (NPY) Y(4) receptor agonist. Toward improving
      the selectivity and potency for Y(4) receptors, we studied the effects of
      dimerizing H-Trp-Arg-Nva-Arg-Tyr-NH(2) using various diamino-dicarboxylic acids
      containing either di-, tri-, or tetramethylene spacers. These parallel dimers,
      2A, 2B, 3, 4A, and 4B, and the corresponding linear tandem dimer and trimer
      analogues, 5 and 6, had enhanced selectivity and affinity for Y(4) receptors
      compared to 1 (Table 1). Substitution of Trp and Nva with Tyr and Leu,
      respectively, as in 2,7-d/l-diaminosuberic acid derivatized dimer, 7, resulted in
      a superior Y(4) selective agonist with picomolar affinity. Intraperitoneal (ip)
      injection of 7 potently inhibited food intake in fasted mice. Moreover, 7 (ip)
      inhibited the food intake in wild-type mice and not in Y(4)(-/-) knock-out mice,
      confirming that the actions of 7 on food intake are not due to global effects,
      but specifically mediated Y(4) receptors.

PMID- 16610811
TI  - Prying apart a water molecule with anionic H-bonding: a comparative spectroscopic
      study of the X-.H2O (X = OH, O, F, Cl, and Br) binary complexes in the 600-3800
      cm(-1) region.
AB  - A detailed picture of the structural distortions suffered by a water molecule in
      direct contact with small inorganic anions (e.g., X = halide) is emerging from a
      series of recent vibrational spectroscopy studies of the gas-phase X-.H2O binary
      complexes. The extended spectral coverage (600-3800 cm(-1)) presently available
      with tabletop laser systems, when combined with versatile argon "messenger"
      techniques for acquiring action spectra of cold complexes, now provides a
      comprehensive survey of how the interaction evolves from an ion-solvent
      configuration into a three-center, two-electron covalent bond as the proton
      affinity of the anion increases. We focus on the behavior of H2O in the X-.H2O (X
      = Br, Cl, F, O, and OH) complexes, which all adopt asymmetric structures where
      one hydrogen atom is H-bonded to the ion while the other is free. The positions
      and intensities of the bands clearly reveal the mechanical consequences of both
      (zero-point) vibrationally averaged and infrared photoinduced excess charge
      delocalization mediated by intracluster proton transfer (X-.H2O --> HX.OH-). The
      fundamentals of the shared proton stretch become quite intense, for example, and
      exhibit extreme red-shifts as the intracluster proton-transfer process becomes
      available, first in the vibrationally excited states (F-.H2O) and then finally at
      the zero-point level (OH-.H2O). In the latter case, the loss of the water
      molecule's independent character is confirmed through the disappearance of the
      approximately 1600 cm(-1) HOH intramolecular bending transition and the dramatic
      (>3000 cm(-1)) red-shift of the shared proton stretch. An unexpected
      manifestation of vibrationally mediated charge transfer is also observed in the
      low frequency region, where the 2 <-- 0 overtones of the out-of-plane frustrated
      rotation of the water are remarkably intense in the Cl-.H2O and Br-.H2O spectra.
      This effect is traced to changes in the charge distribution along the X-.O axis
      as the shared proton is displaced perpendicular to it, reducing the charge
      transfer character of the H-bonding interaction and giving rise to a large
      quadratic contribution to the dipole moment component that is parallel to the
      bond axis. Thus, all of these systems are found to exhibit distinct spectral
      characteristics that can be directly traced to the crucial role of vibrationally
      mediated charge redistribution within the complex.

PMID- 16610812
TI  - Broadband dielectric study of dynamics of poly(vinyl pyrrolidone)-ethylene glycol
      oligomer blends.
AB  - Broadband dielectric measurements for blends of poly(vinyl pyrrolidone) (PVP) and
      ethylene glycol oligomer (EGO) from 0 to 40 wt % PVP were carried out at 25
      degrees C in the frequency range from 20 Hz to 20 GHz. The EGOs used in this
      study were ethylene glycol (EG), diethylene glycol (2EG), and PEG400 (MW = 400).
      For the PVP-EG, -2EG, and -PEG400 blends, relaxation processes caused by the
      motion of EGO in the GHz range and the micro-Brownian motion of the PVP chain at
      10 kHz-1 MHz were observed. Although the PVP-EGO blend is miscible, relaxation
      processes caused by the molecular motion of EGO and the local chain motion of PVP
      were observed individually. The relaxation time of the local chain motion of PVP
      showed a strong PVP concentration dependence and a solvent viscosity dependence,
      which are similar to those reported so far for the solutions in nonpolar
      solvents.

PMID- 16610813
TI  - Fenchone, camphor, 2-methylenefenchone and 2-methylenecamphor: a vibrational
      circular dichroism study.
AB  - We report and discuss the infrared (IR) vibrational circular dichroism (VCD)
      spectra of the enantiomeric pairs of the olefin derivatives of fenchone (1,3,3
      trimethyl-2-methylenebicyclo[2.2.1]heptane) and camphor (1,7,7-trimethyl-2
      methylenebicyclo[2.2.1]heptane), respectively, together with those of the parent
      molecules. The VCD spectra were taken in three spectral regions: the mid-IR
      region, encompassing the fundamental deformation modes, the region of CH
      stretching fundamental modes and the NIR-region between 1100 and 1300 nm, which
      corresponds to the second CH-stretching overtone. The VCD and absorption spectra
      in the first two regions are analyzed by use of current density functional theory
      (DFT) calculations. The NIR region is analyzed by a protocol that consists of the
      use of DFT-based calculations and in assuming local mode behavior: the local mode
      approach is found appropriate for interpreting the absorption spectra and, for
      the moment, acceptable for calculating NIR-VCD spectra. The analysis of the first
      region allows us to track the contribution of the C=O group in the vibrational
      optical activity of C-C stretching modes; notable differences are indeed found in
      olefins and ketones. On the contrary, in the other two regions the VCD spectra of
      olefins and ketones are more similar: in the normal mode region of CH stretching
      fundamentals the spectra are determined by the mutual orientation of the CH
      bonds; in the second overtone local mode region olefins and ketones signals show
      some differences.

PMID- 16610814
TI  - Photodecomposition of peroxides containing a 1,4-bis(phenylethynyl)benzene
      chromophore.
AB  - The photodecomposition dynamics of 1,4-bis(2-[4-tert
      butylperoxycarbonylphenyl]ethynyl)benzene (1) have been compared with those of
      model compounds in the picosecond and nanosecond time domains by various
      photophysical techniques. Ultrafast visible transient absorption spectrometry
      revealed the singlet excited state of 1,4-bis(4-phenylethynyl)benzene (BPB)
      depopulates radiatively with a rate of 1.75 x 10(9) s(-1) and 95% efficiency.
      Phenyl ester moieties attached to the BPB core accelerate intersystem crossing (k
      = 2.8 x 10(8) s(-1)) and reduce the fluorescence quantum yield (phi(FL) = 0.82).
      The peroxide oxygen-oxygen bond of 1 cleaves (k = 3.6 x 10(11) s(-1)) directly
      from the singlet excited state (60% efficiency) causing a highly reduced
      fluorescence yield and leading to formation of aroyloxyl radicals. The next
      reaction step involves decarboxylation of the aroyloxyl radicals. Transient
      absorption signals in the MID IR region correspond to CO2 with the formation rate
      (2.5 x 10(6) s(-1)) as measured by nanosecond transient IR experiments. The
      transient IR spectra of the excited state of BPB, as well as of the aroyloxyl
      radical, evidenced a red shift in the acetylene triple bond absorption indicative
      of a decrease in the bond order. This clearly shows that delocalization of
      excitation energy over the BPB chromophore induces significant structural
      changes. The proposed mechanism is based on the rates of photophysical and
      photochemical channels and involves an additional population channel of the BPB
      triplet excited state from the upper singlet states.

PMID- 16610815
TI  - Tunneling in the loss of hydrogen chloride from isopropyl chloride cation.
AB  - The unimolecular dissociation of isopropyl chloride cation has been investigated
      using mass-analyzed ion kinetic energy spectrometry. The C3H6*+ ion was the only
      product ion in the metastable dissociation. The kinetic energy release
      distribution for the HCl loss was determined. Ab initio molecular orbital
      calculations were performed at the MP2/6-311++G(d,p) level together with single
      point energy calculations at the QCSID(T)/6-311++G(2d,2p) level. The calculations
      show that the molecular ion rearranges to an ion-dipole complex prior to loss of
      HCl via a transition state containing a four-membered ring. The rearrangement
      involves H atom transfer. On the basis of the potential energy surface obtained
      for the loss of HCl and Cl*, the rate constants were calculated by transition
      state statistical theories with considering tunneling effect. From the calculated
      result, it is proposed that the observed HCl loss would occur via tunneling
      through the barrier for isomerization to the ion-dipole complex,
      CH3CHCH2*+...HCl.

PMID- 16610816
TI  - Testing the core/shell model of nanoconfined water in reverse micelles using
      linear and nonlinear IR spectroscopy.
AB  - A core/shell model has often been used to describe water confined to the interior
      of reverse micelles. The validity of this model for water encapsulated in
      AOT/isooctane reverse micelles ranging in diameter from 1.7 to 28 nm (w0 = 2-60)
      and bulk water is investigated using four experimental observables: the hydroxyl
      stretch absorption spectra, vibrational population relaxation times,
      orientational relaxation rates, and spectral diffusion dynamics. The time
      dependent observables are measured with ultrafast infrared spectrally resolved
      pump-probe and vibrational echo spectroscopies. Major progressive changes appear
      in all observables as the system moves from bulk water to the smallest water
      nanopool, w0 = 2. The dynamics are readily distinguishable for reverse micelle
      sizes smaller than 7 nm in diameter (w0 = 20) compared to the response of bulk
      water. The results also demonstrate that the size dependent absorption spectra
      and population relaxation times can be quantitatively predicted using a core
      shell model in which the properties of the core (interior of the nanopool) are
      taken to be those of bulk water and the properties of the shell (water associated
      with the headgroups) are taken to be those of w0 = 2. A weighted sum of the core
      and shell components reproduces the size dependent spectra and the nonexponential
      population relaxation dynamics. However, the same model does not reproduce the
      spectral diffusion and the orientational relaxation experiments. It is proposed
      that, when hydrogen bond structural rearrangement is involved (orientational
      relaxation and spectral diffusion), dynamical coupling between the shell and the
      core cause the water nanopool to display more homogeneous dynamics. Therefore,
      the absorption spectra and vibrational lifetime decays can discern different
      hydrogen bonding environments whereas orientational and spectral diffusion
      correlation functions predict that the dynamics are size dependent but not as
      strongly spatially dependent within a reverse micelle.

PMID- 16610817
TI  - Vibrational spectroscopic studies of the interaction of water with serine.
AB  - The vibrational dynamics of water around serine was investigated by using Raman
      spectroscopy and inelastic incoherent neutron scattering. Experiments with serine
      in deuterium oxide were performed to assist the assignment. The study shows that
      for the serine, the exchange of protons-deuterons on the active -NH3+ and -OH
      groups were relatively easy, whereas there were hardly any exchanged on the -CH
      or -CH2- groups. The main features of the spectra for hydrated samples (versus
      the dry samples) were altered considerably; new sharp peaks in the measured
      spectra appeared, indicating that the hydrogen bonding between water and serine
      had disturbed the structure of the serine molecule.

PMID- 16610818
TI  - Experimental and theoretical investigation on binary semiconductor clusters of
      Bi/Si, Bi/Ge, and Bi/Sn.
AB  - Bi(m)M(n)- (M = Si, Ge, Sn) binary cluster anions are generated by using laser
      ablation on mixtures of Bi and M (M = Si, Ge, Sn) samples and studied by
      reflectron time-of-flight mass spectrometer (RTOF-MS) in the gas phase. Some
      magic number clusters are present in the mass spectra which indicate that they
      are in stable structures. For small anions (m + n < or = 6), their structures are
      investigated with the DFT method and the energetically lowest lying structures
      are obtained. For the binary anionic clusters with the same composition
      containing Si, Ge, and Sn, they share similar geometric and electronic structure
      in the small size except that BiSi3-, BiSi5-, Bi2Si2-, Bi2Si3-, and Bi4Sn2- are
      different for the lowest energetic structures, and the ground states for all the
      anions are in their lowest spin states. The calculated VDE (vertical detachment
      energy) and binding energy confirm the obviously magic number cluster of BiM4- (M
      = Si, Ge, Sn), which agrees with the experimental results.

PMID- 16610819
TI  - Solvation of Na+ in argon clusters.
AB  - The structures and stabilities of Ar(n)Na+ clusters (n < or = 54) are
      investigated using atomistic potentials fitted to reproduce ab initio
      calculations performed at the coupled-cluster level on the smaller clusters.
      Polarization effects are described using either the interaction between dipoles
      induced by the sodium ion, or a small charge transfer in the framework of a
      fluctuating charges model. In both models, extra three-body contributions of the
      Axilrod-Teller type are also included between the sodium ion and all pairs of
      argon atoms. The two models predict essentially similar growth patterns, and a
      transition in the metal ion coordination from 8 (square antiprism) to 12
      (icosahedron) is seen to occur near n = 50, in response to the intrasolvent
      constraints.

PMID- 16610820
TI  - Fluorescence and REMPI spectroscopy of jet-cooled isolated 2-phenylindene in the
      S1 state.
AB  - We investigated the spectroscopy of the first excited singlet electronic state S1
      of 2-phenylindene using both fluorescence excitation spectroscopy and resonantly
      enhanced multiphoton ionization spectroscopy. Moreover, we investigated the
      dynamics of the S1 state by determining state-selective fluorescence lifetimes up
      to an excess energy of approximately 3400 cm(-1). Ab initio calculations were
      performed on the torsional potential energy curve and the equilibrium and
      transition state geometries and normal-mode frequencies of the first excited
      singlet state S1 on the CIS level of theory. Numerous vibronic transitions were
      assigned, especially those involving the torsional normal mode. The torsional
      potentials of the ground and first excited electronic states were simulated by
      matching the observed and calculated torsional frequency spacings in a least
      squares fitting procedure. The simulated S1 potential showed very good agreement
      with the ab initio potential calculated on the CIS/6-31G(d,p) level of theory.
      TDDFT energy corrections improved the match with the simulated S(1) torsional
      potential. The latter calculation yielded a torsional barrier of V2 = 6708 cm(
      1), and the simulation a barrier of V2 = 6245 cm(-1). Ground-state normal-mode
      frequencies were calculated on the B3LYP/6-31G(d,p) level of theory, which were
      used to interpret the infrared spectrum, the FDS spectrum of the transition and
      hot bands of the FES spectrum. The fluorescence intensities of the nu49 overtone
      progression could reasonably be reproduced by considering the geometry changes
      upon electronic excitation predicted by the ab initio calculations. On the basis
      of the torsional potential calculations, it could be ruled out that the uniform
      excess energy dependence of the fluorescence lifetimes is linked to the torsional
      barrier in the excited state. The rotational band contour simulation of the
      transition yielded rotational constants in close agreement to the ab initio
      values for both electronic states. Rotational coherence signals were obtained by
      polarization-analyzed, time-resolved measurements of the fluorescence decay of
      the transition. The simulation of these signals yielded corroborating evidence as
      to the quality of the ab initio calculated rotational constants of both states.
      The origin of the anomalous intensity discrepancy between the fluorescence
      excitation spectrum and the REMPI spectrum is discussed.

PMID- 16610821
TI  - Threshold photoelectron-photoion coincidence spectroscopy: dissociation dynamics
      and thermochemistry of Ge(CH3)4, Ge(CH3)3Cl, and Ge(CH3)3Br.
AB  - Threshold photoelectron-photoion coincidence spectroscopy (TPEPICO) has been used
      to investigate the gas-phase ionic dissociation energies and thermochemistry of
      Me4Ge and Me3GeX, (Me = methyl; X = Cl, Br) molecules. The 0 K dissociation
      onsets for these species have been measured from the breakdown diagram and the
      ion time-of-flight distributions, which were modeled with the statistical RRKM
      theory and DFT calculations. The measured 0 K dissociative photoionization onsets
      were as follows: Me3Ge+ + Me (9.826 +/- 0.010 eV); Me3Ge+ + Cl (10.796 +/- 0.040
      eV); Me3Ge+ + Br (10.250 +/- 0.011 eV); Me2GeCl+ + Me (10.402 +/- 0.010 eV); and
      Me2GeBr+ + Me (10.333 +/- 0.020 eV). These onsets were used to obtain new values
      for delta(f)H(degrees)298 (in kJ/mol) of the neutral molecules Me3GeCl (-239.8 +/
      5.7) and Me3GeBr (-196.5 +/- 4.3), and also for the following ionic species:
      Me3Ge+ (682.3 +/- 4.1), Me2GeCl+ (621.1 +/- 5.8), and Me2GeBr+ (657.8 +/- 4.7).

PMID- 16610822
TI  - Photoisomerizations of N4-hydroxycytosines.
AB  - A series of N4-hydroxycytosines, unsubstituted or substituted with methyl groups
      at N3 or C5 atoms of the heterocyclic ring, was studied using the matrix
      isolation method. Depending on the absence or presence of the methyl substituent
      at N3 or C5 atoms (or at both of them) the syn or anti form of the compounds (or
      a mixture of both forms) was trapped from the gas phase into a low-temperature
      matrix. Upon UV (lambda > 295 nm) irradiation of the matrixes the syn --> anti as
      well as the anti --> syn photoisomerization reactions were observed. The syn and
      anti isomers of N4-hydroxycytosines were identified by comparing their
      experimental IR spectra with the theoretical spectra calculated at the
      DFT(B3LYP)/6-31G(d,p) level. For the majority of the studied compounds, the UV
      induced reactions led to a photostationary state. The position of the final
      photostationary state was found to be a sensitive function of weak interactions
      of a studied N4-hydroxycytosine with the matrix environment: solid argon or solid
      nitrogen. However, not all of the studied photoisomerizations led to a classical
      photostationary state. For some of the investigated N4-hydroxycytosines, the
      position of the photostationary state was shifted very strongly in favor of the
      photoproduct, whereas for some others the position was shifted so strongly in
      favor of the starting isomer that no photoisomerization was observed. These
      experimental findings were elucidated by theoretical investigations of the
      potential energy surfaces of the ground (S0) and first excited (S1) electronic
      states of N4-hydroxycytosine. The crucial result of these calculations (carried
      out at the CASSCF level) was the localization of a conical intersection between
      S0 and S1 at a structure with perpendicular orientation of the hydroxylimino
      group with respect to the heterocyclic ring.

PMID- 16610823
TI  - Determination of the electron affinity of the acetyloxyl radical (CH3COO) by low
      temperature anion photoelectron spectroscopy and ab initio calculations.
AB  - The electronic structure and electron affinity of the acetyloxyl radical (CH3COO)
      were investigated by low-temperature anion photoelectron spectroscopy and ab
      initio calculations. Photoelectron spectra of the acetate anion (CH3COO-) were
      obtained at two photon energies (355 and 266 nm) and under three different
      temperatures (300, 70, and 20 K) with use of a new low-temperature ion-trap
      photoelectron spectroscopy apparatus. In contrast to a featureless spectrum at
      300 K, a well-resolved vibrational progression corresponding to the OCO bending
      mode was observed at low temperatures in the 355 nm spectrum, yielding an
      accurate electron affinity for the acetyloxyl radical as 3.250 +/- 0.010 eV. This
      experimental result is supported by ab initio calculations, which also indicate
      three low-lying electronic states observed in the 266 nm spectrum. The
      calculations suggest a 19 degrees decrease of the OCO angle upon detaching an
      electron from acetate, consistent with the vibrational progression observed
      experimentally.

PMID- 16610824
TI  - Electronic and vibrational spectroscopy and vibrationally mediated
      photodissociation of V+(OCO).
AB  - Electronic spectra of gas-phase V+(OCO) are measured in the near-infrared from
      6050 to 7420 cm(-1) and in the visible from 15,500 to 16,560 cm(-1), using
      photofragment spectroscopy. The near-IR band is complex, with a 107 cm(-1)
      progression in the metal-ligand stretch. The visible band shows clearly resolved
      vibrational progressions in the metal-ligand stretch and rock, and in the OCO
      bend, as observed by Brucat and co-workers. A vibrational hot band gives the
      metal-ligand stretch frequency in the ground electronic state nu3'' = 210 cm(-1).
      The OCO antisymmetric stretch frequency in the ground electronic state (nu1'') is
      measured by using vibrationally mediated photodissociation. An IR laser
      vibrationally excites ions to nu1'' = 1. Vibrationally excited ions selectively
      dissociate following absorption of a second, visible photon at the nu1' = 1 <--
      nu1'' = 1 transition. Rotational structure in the resulting vibrational action
      spectrum confirms that V+(OCO) is linear and gives nu1'' = 2392.0 cm(-1). The OCO
      antisymmetric stretch frequency in the excited electronic state is nu1' = 2368
      cm(-1). Both show a blue shift from the value in free CO2, due to interaction
      with the metal. Larger blue shifts observed for complexes with fewer ligands
      agree with trends seen for larger V+(OCO)n clusters.

PMID- 16610825
TI  - Combined quantum chemical density functional theory and spectroscopic Raman and
      UV-vis-NIR study of oligothienoacenes with five and seven rings.
AB  - In this article, we report the characterization of novel oligothienoacenes with
      five and seven fused thiophene rings, materials with potential applications in
      organic electronics. In contrast to usual alpha-linked oligothiophenes, these
      fused oligothiophenes have a larger band gap than most semiconductors currently
      used in the fabrication of organic field-effect transistors (OFETs) and therefore
      they are expected to be more stable in air. The synthesis of these fused-ring
      oligomers was motivated by the notion that a more rigid and planar structure
      should reduce defects (such as torsion about single bonds between alpha-linked
      units or S-syn defects) and thus improve conjugation for better charge-carrier
      mobility. The conjugational properties of these two molecular materials have been
      investigated by means of FT-Raman spectroscopy, revealing that conjugation still
      increases in passing from the five-ring oligomer to that with seven-rings. DFT
      and TDDFT quantum chemical calculations have been performed, at the B3LYP/6-31G
      level, to assess information regarding the minimum-energy molecular structure,
      topologies, and absolute energies of the frontier molecular orbitals (MOs.)
      around the gap, vibrational normal modes related to the main Raman features, and
      vertical one-electron excitations giving rise to the main optical absorptions.

PMID- 16610826
TI  - TG-FTIR, DSC, and quantum-chemical studies on the thermal decomposition of
      quaternary ethylammonium halides.
AB  - The thermal decomposition of quaternary ethylammonium chloride, bromide, and
      iodide has been studied using the experimental techniques of thermal gravimetry
      coupled to Fourier transform infrared spectroscopy (TG-FTIR) and differential
      scanning calorimetry (DSC) as well as the density functional theory (DFT) and MP2
      quantum-chemical methods. These compounds decompose in a one-step process, and
      the almost perfect agreement between the experimental IR spectra and those
      predicted at the B3LYP/6-311G(d,p) level demonstrates for the first time that
      decomposition produces an equimolar mixture of triethylamine and a haloethane.
      The respective experimental enthalpies of dissociation of the chloride, bromide,
      and iodide are 158, 181, and 195 kJ/mol. These values correlate well with the
      calculated enthalpies of dissociation based on crystal lattice energies and
      quantum-chemical thermodynamic barriers. The experimental activation barriers
      were derived from the least-squares fit of the F1 kinetic model (first-order
      process) to thermogravimetric traces. These estimates are 184, 286, and 387
      kJ/mol for chloride, bromide, and iodide, respectively, and agree well with the
      theoretical calculations. It has been demonstrated that the theoretical approach
      assumed in this work is capable of predicting the relevant characteristics of the
      thermal decomposition of solids with experimental accuracy. DFT methodology is
      recommended for the quantum-chemical part of the model: B3LYP for evaluating the
      thermodynamic barriers and MPW1K for assessing the activation characteristics.
      These quantum-chemical data then have to be combined with crystal lattice
      energies. The latter should be calculated using both electrostatic and repulsion
      dispersion terms.

PMID- 16610827
TI  - Nuclear magnetic resonance studies of convection in the 1,4-cyclohexanedione
      bromate-acid reaction.
AB  - The manifestation and development of convection during pattern formation in the
      1,4-cyclohexanedione-acid-bromate reaction was investigated using pulsed gradient
      spin-echo nuclear magnetic resonance (PGSE NMR) experiments. An apparatus was
      devised that enabled convection to be probed inside an NMR spectrometer and
      prevented hydrodynamic motion arising from extraneous sources, such as poor
      mixing or temperature gradients imposed by the experimental setup. PGSE
      experiments were performed concurrently with magnetic resonance imaging (MRI)
      experiments to show that convection arose spontaneously from inhomogeneities
      associated with the chemical patterns. Quantitative data on diffusion
      coefficients and hydrodynamic velocities are reported.

PMID- 16610828
TI  - High-temperature reactions of OH radicals with benzene and toluene.
AB  - The rate constants for the reactions of OH radicals with benzene and toluene have
      been measured directly by a shock tube/pulsed laser-induced fluorescence imaging
      method at high temperatures. The OH radicals were generated by the thermal
      decomposition of nitric acid or tert-butyl hydroperoxide. The derived Arrhenius
      expressions for the rate constants were k(OH + benzene) = 8.0 x 10(-11) exp(-26.6
      kJ mol(-1)/RT) [908-1736 K] and k(OH + toluene) = 8.9 x 10(-11) exp(-19.7 kJ mol(
      1)/RT) [919-1481 K] in the units of cubic centimeters per molecule per second.
      Transition-state theory (TST) calculations based on quantum chemically predicted
      energetics confirmed the dominance of the H-atom abstraction channel for OH +
      benzene and the methyl-H abstraction channel for OH + toluene in the experimental
      temperature range. The TST calculation indicated that the anharmonicity of the C
      H-O bending vibrations of the transition states is essential to reproduce the
      observed rate constants. Possible implications to the other analogous H-transfer
      reactions were discussed.

PMID- 16610829
TI  - Accurate ab initio binding energies of the benzene dimer.
AB  - Accurate binding energies of the benzene dimer at the T and parallel displaced
      (PD) configurations were determined using the single- and double-coupled cluster
      method with perturbative triple correction (CCSD(T)) with correlation-consistent
      basis sets and an effective basis set extrapolation scheme recently devised. The
      difference between the estimated CCSD(T) basis set limit electronic binding
      energies for the T and PD shapes appears to amount to more than 0.3 kcal/mol,
      indicating the PD shape is a more stable configuration than the T shape for this
      dimer in the gas phase. This conclusion is further strengthened when a
      vibrational zero-point correction to the electronic binding energies of this
      dimer is made, which increases the difference between the two configurations to
      0.4-0.5 kcal/mol. The binding energies of 2.4 and 2.8 kcal/mol for the T and PD
      configurations are in good accord with the previous experimental result from
      ionization potential measurement.

PMID- 16610830
TI  - Theoretical study of the relationship between the nearest-neighbor exchange
      coupling interactions and the number of peripheral complexes in the cyano-bridged
      CrMn6(CN)6 and CrMn2(CN)2 clusters.
AB  - A theoretical density functional study of the relationship between the nearest
      neighbor constants and the number of peripheral complexes in the cyano-bridged
      [Cr[CNMn(salen)(H2O)]6]3+ and [(5-Brsalen)2(H2O)2Mn2Cr(CN)6] clusters is
      presented. Two approaches show that the antiferromagnetic coupling interactions
      between nearest neighbors decrease with the increase of the number of peripheral
      complexes, although the second approach provides better results using several
      exchange-correlation functionals. The first approach consisted of evaluating the
      exchange coupling constant J(ij) between two paramagnetic metal centers i and j
      in the hexanuclear molecule by calculating the energy differences between the
      highest and broken-symmetry spin states of a model molecule in which metal atoms
      except for i and j are substituted by diamagnetic Zn(II) cations, while the
      second consisted of calculating the different spin-state energies of hexanuclear
      complexes and using the Heisenberg Hamiltonian to obtain the exchange coupling
      constants between different metal centers. Moreover, Kahn's qualitative theory
      succeeded in being applied to interpret the trend.

PMID- 16610831
TI  - Bridging the gap between the topological and orbital description of hydrogen
      bonding: the case of the formic acid dimer and its sulfur derivatives.
AB  - Several molecular descriptors, based on topological approaches as well as on a
      more traditional orbital-based decomposition, have been used to asses relations
      with hydrogen bond strengths in a series of formic acid dimers and its sulfur
      derivatives. Particular attention has been devoted to the analysis of the core
      valence bifurcation topological index and to the bond order index. Their values
      are seen to be linearly related to bond energies estimated through a bond-energy
      bond-order relationship; also, the mean value of the topological index appears to
      be related to the complexation energy computed by methods based on density
      functional theory. The dependence of the index upon the donor-acceptor couple in
      relation to its applicability is discussed.

PMID- 16610832
TI  - Aromaticity measures from fuzzy-atom bond orders (FBO). The aromatic fluctuation
      (FLU) and the para-delocalization (PDI) indexes.
AB  - In the past few years, there has been a growing interest for aromaticity measures
      based on electron density descriptors, the para-delocalization (PDI) and the
      aromatic fluctuation (FLU) indexes being two recent examples. These aromaticity
      indexes have been applied successfully to describe the aromaticity of carbon
      skeleton molecules. Although the results obtained are encouraging, because they
      follow the trends of other existing aromaticity measures, their calculation is
      rather expensive because they are based on electron delocalization indexes (DI)
      that involve cumbersome atomic integrations. However, cheaper electron-sharing
      indexes (ESIs), which in principle could play the same role as the DI in such
      aromaticity calculations, can be found in the literature. In this letter we show
      that PDI and FLU can be calculated using fuzzy-atom bond order (FBO) measures
      instead of DIs with an important saving of computing time. In addition, a basis
      set-dependence study is performed to assess the reliability of these measures.
      FLU and PDI based on FBO are shown to be both good aromaticity indexes and almost
      basis-set-independent measures. This result opens up a wide range of
      possibilities for PDI and FLU to also be calculated on large organic systems. As
      an example, the DI and FBO-based FLU and PDI indexes have also been calculated
      and compared for the C60 molecule.

PMID- 16610833
TI  - Study of molecular quantum similarity of enantiomers of amino acids.
AB  - Molecular quantum similarity is evaluated for enantiomers in the case of
      molecules showing conformational flexibility, using our earlier proposed
      Boltzmann weighted similarity index. The conformers of the enantiomers of the
      amino acids alanine, asparagine, cysteine, leucine, serine, and valine were
      examined. Next to studying global indices, the evaluation of local similarity is
      carried out using our earlier proposed local similarity index based on the
      Hirshfeld partitioning, to further illustrate Mezey's holographic electron
      density theorem in chiral systems and to quantify dissimilarity of enantiomers.

PMID- 16610834
TI  - Comparative DFT study of van der Waals complexes: rare-gas dimers, alkaline-earth
      dimers, zinc dimer, and zinc-rare-gas dimers.
AB  - Recent interest in the application of density functional theory prompted us to
      test various functionals for the van der Waals interactions in the rare-gas
      dimers, the alkaline-earth metal dimers, zinc dimer, and zinc-rare-gas dimers. In
      the present study, we report such tests for 18 DFT functionals, including both
      some very recent functionals and some well-established older ones. We draw the
      following conclusions based on the mean errors in binding energies and complex
      geometries: (1) B97-1 gives the best performance for predicting the geometry of
      rare-gas dimers, whereas M05-2X and B97-1 give the best energetics for rare-gas
      dimers. (2) PWB6K gives the best performance for the prediction of the geometry
      of the alkaline-earth metal dimers, zinc dimers, and zinc-rare-gas dimers. M05-2X
      gives the best energetics for the metal dimers, whereas B97-1 gives the best
      energetics for the zinc-rare-gas dimers. (3) The M05 functional is unique in
      providing good accuracy for both covalent transition-metal dimers and van der
      Waals metal dimers. (4) The combined mean percentage unsigned error in geometries
      and energetics shows that M05-2X and MPWB1K are the overall best methods for the
      prediction of van der Waals interactions in metal and rare-gas van der Waals
      dimers.

PMID- 16610835
TI  - Enthalpy of formation of the cyclopentadienyl radical: photoacoustic calorimetry
      and ab initio studies.
AB  - The gas-phase C-H bond dissociation enthalpy (BDE) in 1,3-cyclopentadiene has
      been determined by time-resolved photoacoustic calorimetry (TR-PAC) as 358 +/- 7
      kJ mol(-1). Theoretical results from ab initio complete basis-set approaches,
      including the composite CBS-Q and CBS-QB3 procedures, and basis-set extrapolated
      coupled-cluster calculations (CCSD(T)) are reported. The CCSD(T) prediction for
      the C-H BDE of 1,3-cyclopentadiene (353.3 kJ mol(-1)) is in good agreement with
      the TR-PAC result. On the basis of the experimental and the theoretical values
      obtained, we recommend 355 +/- 8 kJ mol(-1) for the C-H BDE of 1,3
      cyclopentadiene and 271 +/- 8 kJ mol(-1) for the enthalpy of formation of
      cyclopentadienyl radical.

PMID- 16610836
TI  - O-H stretch modes of dodecahedral water clusters: a statistical ab initio study.
AB  - Infrared frequencies calculations were carried out for 20 (H2O)20 water clusters
      obeying the 5(12) dodecahedral geometry, optimized at the B3LYP/6-311++G** level.
      Their combined spectra contained 800 O-H stretch modes, ranging from 2181 to 3867
      cm(-1) (unscaled), which were treated and studied as a database. Of these, 752
      modes (94%) could be assigned to a single dominant O-H stretch. These 752 were
      classified into five subdatabases depending on the local H-bond type of the
      dominant stretch. The frequency (nu) was correlated with the O-H distance
      (b(OH)), with H-bond length (R(OO)) where applicable, and with other variables.
      The parameter b(OH) alone accounted for 96-99% of the variance in nu for
      stretches in H-bonds. The correlation with R(OO) is substantially weaker. Normal
      modes were classified as "high ratio" or "low ratio" depending upon the mode's
      distribution of kinetic energy among the O-H bonds. High-ratio modes (389 modes,
      or 49% of our sample) are modeled well as a single oscillator undergoing small
      perturbations by weak coupling from other oscillators. Low-ratio modes involve
      strong coupling with at least one other O-H stretch for which b(OH2) is close to
      b(OH). The IR intensities of modes vary widely but can be explained in terms of a
      single equation giving dipole moment derivatives as a function of b(OH). For the
      lowest-energy (H2O)20 clusters, their IR stretch spectra contained eight
      distinguishable absorption bands. An explanation for eight bands in terms of the
      theory of polyhedral water clusters is offered.

PMID- 16610837
TI  - Ab initio study of [n.n]paracyclophane (n = 2, 3) complexes with cations:
      unprecedented through-space substituent effects.
AB  - Several cation-pi complexes between substituted [n.n]paracyclophanes (n = 2, 3)
      and cations have been studied using high level ab initio calculations. The
      chemical substitution at the aromatic ring that is not interacting with the
      cation has a strong influence upon the binding energy. This strong through-space
      substituent effect has been studied using the "atoms-in-molecules" theory, which
      has been found useful to explain the energetic results.

PMID- 16610838
TI  - Inelastic neutron scattering spectrum of cyclotrimethylenetrinitramine: a
      comparison with solid-state electronic structure calculations.
AB  - Solid-state geometry optimizations and corresponding normal-mode analysis of the
      widely used energetic material cyclotrimethylenetrinitramine (RDX) were performed
      using density functional theory with both the generalized gradient approximation
      (BLYP and BP functionals) and the local density approximation (PWC and VWN
      functionals). The structural results were found to be in good agreement with
      experimental neutron diffraction data and previously reported calculations based
      on the isolated-molecule approximation. The vibrational inelastic neutron
      scattering (INS) spectrum of polycrystalline RDX was measured and compared with
      simulated INS constructed from the solid-state calculations. The vibrational
      frequencies calculated from the solid-state methods had average deviations of 10
      cm(-1) or less, whereas previously published frequencies based on an isolated
      molecule approximation had deviations of 65 cm(-1) or less, illustrating the
      importance of including crystalline forces. On the basis of the calculations and
      analysis, it was possible to assign the normal modes and symmetries, which agree
      well with previous assignments. Four possible "doorway modes" were found in the
      energy range defined by the lattice modes, which were all found to contain
      fundamental contributions from rotation of the nitro groups.

PMID- 16610839
TI  - Conformational preference in heteroatomic analogues of ethane, H3X-YH3 (X = B,
      Al; Y = N, P): implications of charge transfer.
AB  - Quantum chemical conformational analysis for electron donor-acceptor (EDA)
      systems, H3B-NH3, H3B-PH3, H3Al-NH3 and H3Al-PH3, has been performed. For H3B-NH3
      and H3B-PH3, the rotational barrier is found to be invariant with an increase in
      the central bond (X-Y) length. For H3Al-NH3 and H3Al-PH3, however, the rotational
      barrier increases with an increase in the central bond length. Decomposition of
      the total energy into various components and their contributions to the frontier
      orbitals (HOMO, HOMO-1, HOMO-2 and HOMO-3) have been analyzed in detail to
      explain the origin of such anomalous changes in the rotational barrier. Charge
      transfer and favorable "back bonding" are found to be the crucial factors
      governing the variations in the rotational barrier for such systems.

PMID- 16610840
TI  - Mono- and bichromatic electron dynamics: LiH, a test case.
AB  - This paper describes an electron dynamics method where the time dependence of an
      external oscillating electric field is the perturbing part of the Hamiltonian.
      Application of the electric field induces charge movement inside the molecule and
      electronic transitions between the molecular orbitals. The test system is the
      neutral LiH molecule. The method is applied to wave functions calculated using
      the B3LYP (hybrid) density functional, with the STO-3G and the 6-31+G basis sets.
      The molecule undergoes full population inversion between the HOMO and the LUMO
      when the electric field is in resonance with the HOMO-LUMO energy gap. The
      magnitude of the electric field directly affects the rate at which electronic
      transitions occur and the rate at which charges move between lithium and hydrogen
      atoms. The method is used to model both monochromatic and bichromatic multiphoton
      effects in LiH. Monochromatic one-, two- and three-photon transitions occur
      between the HOMO, LUMO and two other virtual orbitals. There is evidence of both
      [1+2] direct and [1+1+1] stepwise multiphoton transitions. Bichromatically, two
      "laser" pulses are applied at different frequencies. Electronic transitions can
      be fine-tuned to occur via pre-specified pathways of virtual molecular orbitals.

PMID- 16610841
TI  - First principles calculation of the mechanical compression of two organic
      molecular crystals.
AB  - The mechanical compression curves for the organic molecular crystals 1,1-diamino
      2,2-dinitroethylene and beta-octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine
      (beta-HMX) are calculated using the Hartree-Fock approximation to the solutions
      of the many-body Schrodinger equation for a periodic system as implemented in the
      computer program CRYSTAL. No correction was made for basis set superposition
      error. The equilibrium lattice parameters are reproduced to within 1% of reported
      experimental values. Pressure values on the isotherm also agree well with
      reported experimental values. To obtain accurate results, the relaxation of all
      the atomic coordinates as well as the lattice parameters under a fixed volume
      constraint was required.

PMID- 16610842
TI  - Synergism of porphyrin-core saddling and twisting of meso-aryl substituents.
AB  - The structural chemistry of meso-aryl-substituted porhyrins has uncovered a
      bewildering variety of macrocycle distortions. Saddling angles range up to 40
      degrees , while the plane of the phenyl groups at the meso positions may be
      anywhere between perpendicular to the porphyrin plane (theta = 90 degrees) and
      tilted to quite acute angles (theta = 30 degrees or even less). These two
      distortions appear to be correlated. This has naturally been explained by steric
      hindrance: when the phenyls rotate toward the porphyrin plane, for instance,
      coerced by packing forces, the pyrrole rings can alleviate the steric hindrance
      by tilting away to a saddled conformation. We demonstrate, however, that the two
      motions are intrinsically coupled by electronic factors and are correlated even
      in the absence of external forces. A saddling motion makes it sterically possible
      for the phenyl rings to rotate toward the porphyrin plane, which will always
      happen because of increasingly favorable pi-conjugation interaction with smaller
      angles theta. The considerable energy lowering due to pi conjugation counteracts
      the energy cost of the saddling, making the concerted saddling/rotation motion
      very soft. Unsubstituted meso-aryl porphyrins just do not distort, but an
      additional driving force may tip the balance in favor of the combined distortion
      motion. Internal forces having this effect are repulsion of the four hydrogens
      that occupy the central hole of the ring in porphyrin diacids but also steric
      repulsion in peripherally crowded porphyrins. These findings lead to a
      clarification and systematization of the observed structural variety, which
      indeed shows a remarkable correlation between saddling and phenyl ring tilting.

PMID- 16610843
TI  - Quantitative single-molecule conformational distributions: a case study with poly
      (L-proline).
AB  - Precise measurement of the potential of mean force is necessary for a fundamental
      understanding of the dynamics and chemical reactivity of a biological
      macromolecule. The unique advantage provided by the recently developed constant
      information approach to analyzing time-dependent single-molecule fluorescence
      measurements was used with maximum entropy deconvolution to create a procedure
      for the accurate determination of molecular conformational distributions, and
      analytical expressions for the errors in these distributions were derived. This
      new method was applied to a derivatized poly(L-proline) series, P(n)CG3K(biotin)
      (n = 8, 12, 15, 18, and 24), using a modular, server-based single-molecule
      spectrometer that is capable of registering photon arrival times with a
      continuous-wave excitation source. To account for potential influence from the
      microscopic environment, factors that were calibrated and corrected molecule by
      molecule include background, cross-talk, and detection efficiency. For each
      single poly(L-proline) molecule, sharply peaked Forster type resonance energy
      transfer (FRET) efficiency and distance distributions were recovered, indicating
      a static end-to-end distance on the time scale of measurement. The experimental
      distances were compared with models of varying rigidity. The results suggest that
      the 23 angstroms persistence length wormlike chain model derived from experiments
      with high molecular weight poly(L-proline) is applicable to short chains as well.

PMID- 16610844
TI  - Excited mixed-valence states of symmetrical donor-acceptor-donor pi systems.
AB  - We investigated the spectroscopic properties of a series of four bistriarylamine
      donor-pi-bridge-donor D-pi-D compounds (dimers), composed of two asymmetric
      triarylamine chromophores (monomers). UV/vis, fluorescence, and transient
      absorption spectra were recorded and compared with those of the corresponding D
      pi monomers. Bilinear Lippert-Mataga plots indicate a major molecular
      reorganization of the excited state in polar media for all compounds. The excited
      states of the dimers are described as mixed-valence states that show, depending
      on the chemical nature of the pi bridge, a varying amount of interactions
      (couplings). We found that superradiant emission, that is, an enhancement of the
      fluorescence rate in the dimer, is observed only in the case of weak and medium
      coupling. Whether the first excited-state potential energy surface of the dimers
      is described by single minimum or a double minimum potential depends on the
      solvent polarity and the electronic coupling. In the latter case, the dimer
      relaxes in a symmetry broken CT state with partial positive charge at the
      triarylamine donor and negative charge at the pi bridge. The [2.2]paracyclophane
      bridged dimer is an example of a weakly coupled system because the spectroscopic
      behavior is very similar to the corresponding p-xylene monomer. In contrast,
      anthracene as well as p-xylene bridges mediate a stronger coupling and reveal a
      significant cooperative influence on the optical properties.

PMID- 16610845
TI  - Synthesis and photophysical properties of silicon phthalocyanines with axial
      siloxy ligands bearing alkylamine termini.
AB  - Eleven silicon phthalocyanines which can be grouped into two homologous series
      [SiPc[OSi(CH3)2(CH2)(n)N(CH3)2]2, n = 1-6 (series 1), and
      SiPc[OSi(CH3)2(CH2)3N((CH2)(n)H)2]2, n = 1-6 (series 2)] as well as an analogous
      phthalocyanine, SiPc[OSi(CH3)2(CH2)3NH2]2, were synthesized. The ground state
      absorption spectra, the triplet state dynamics, and singlet oxygen quantum yields
      of 10 of these phthalocyanines were measured. All compounds displayed similar
      ground state absorption spectral properties in dimethylformamide solution with
      single Q band maxima at 668 +/- 2 nm and B band maxima at 352 +/- 1 nm.
      Photoexcitation of all compounds in the B bands generated the optical absorptions
      of the triplet states which decayed with lifetimes in the hundreds of
      microseconds region. Oxygen quenching bimolecular rate constants near 2 x 10(9)
      M(-1) s(-1) were measured, indicating that energy transfer to oxygen was
      exergonic. Singlet oxygen quantum yields, phi(delta), were measured, and those
      phthalocyanines in which the axial ligands are terminated by dimethylamine
      residues at the end of alkyl chains having four or more methylene links exhibited
      yields near > or = 0.35. Others gave singlet oxygen quantum yields near 0.2, and
      still others showed singlet oxygen yields of <0.1. The reduced singlet oxygen
      yields are probably caused by a charge transfer quenching of the 1pi,pi* state of
      the phthalocyanine by interaction with the lone pair electrons on the nitrogen
      atoms of the amine termini. In some cases, these can approach and interact with
      the electronically excited pi-framework, owing to diffusive motions of the
      flexible oligo-methylene tether.

PMID- 16610847
TI  - Particles coming together: electron centers in adjoined TiO2 nanocrystals.
AB  - To include particle attachment and porosity of nanostructured materials in the
      discussion of their electronic properties is critical to our understanding of
      charge transfer across grain boundaries. We report the condensation of isolated
      TiO(2) nanocrystals via the application of a simple hydration-dehydration cycle.
      After contact with water and subsequent removal of adsorbed water, these
      nanocrystals form a mesoporous structure with altered properties as compared with
      the original material: first, the energy needed for defect formation is
      substantially reduced, and second, electron paramagnetic resonance measurements
      reveal the presence of polarizable conduction band electrons not detectable in
      samples which have not been in contact with water.

PMID- 16610848
TI  - Infrared spectroscopic characterization of [2]rotaxane molecular switch tunnel
      junction devices.
AB  - Langmuir-Blodgett monolayers of a bistable [2]rotaxane were prepared at packing
      densities of 118, 73, and 54 A(2)/molecule. The monolayers were both
      characterized via infrared spectroscopy before and after evaporation of a 2 nm
      film of titanium and incorporated into molecular switch tunnel junction devices.
      The study suggests that the evaporation process primarily affects portions of the
      molecule exposed to the metal atom source. Thus, in tightly packed monolayers (73
      and 54 A(2)/molecule), only the portions of the [2]rotaxane that are present at
      the molecule/air interface are clearly affected, leaving key functionality
      necessary for switching intact. Monolayers transferred at a lower pressure (118
      A(2)/molecule) exhibit nonspecific damage and poor switching behavior following
      Ti deposition. These results indicate that tightly packed monolayers and
      sacrificial functionality displayed at the molecule/air interface are important
      design principles for molecular electronic devices.

PMID- 16610849
TI  - Acidity of frozen electrolyte solutions.
AB  - Ice is selectively intolerant to impurities. A preponderance of implanted anions
      or cations generates electrical imbalances in ice grown from electrolyte
      solutions. Since the excess charges are ultimately neutralized via interfacial
      (H(+)/HO(-)) transport, the acidity of the unfrozen portion can change
      significantly and permanently. This insufficiently recognized phenomenon should
      critically affect rates and equilibria in frozen media. Here we report the
      effective (19)F NMR chemical shift of 3-fluorobenzoic acid as in situ probe of
      the acidity of extensively frozen electrolyte solutions. The sign and magnitude
      of the acidity changes associated with freezing are largely determined by
      specific ion combinations, but depend also on solute concentration and/or the
      extent of supercooling. NaCl solutions become more basic, those of
      (NH(4))(2)SO(4) or Na(2)SO(4) become more acidic, while solutions of the 2-(N
      morpholino)ethanesulfonic acid zwitterion barely change their acidity upon
      freezing. We discuss how acidity scales based on solid-state NMR measurements
      could be used to assess the degree of ionization of weak acids and bases in
      frozen media.

PMID- 16610850
TI  - Elucidation of codoping effects on the solubility enhancement of Er3+ in SiO2
      glass: striking difference between Al and P codoping.
AB  - The codoping effect mechanism of Al and P on the solubility enhancement of Er(3+)
      ion in SiO(2) glass was clarified by electron spin-echo envelope modulation
      spectroscopy. It turned out that doped P ions preferentially coordinate to the
      Er(3+) ion to form a "solvation shell structure", and the environment is similar
      to that in phosphate glass, while doped Al ions do not form such a selective
      solvation structure, taking octahedral coordination. This striking difference
      indicates that the primary roles of the P-doping and the Al-doping are attributed
      to "enthalpy of mixing" and to "entropy of mixing", respectively.

PMID- 16610851
TI  - Chemical applications of hyper-Rayleigh scattering in solution.
AB  - Hyper-Rayleigh or second harmonic Rayleigh scattering (HRS or SHLS) has been
      employed to measure equilibrium physical properties of molecules in solution. It
      has been utilized in our laboratory to obtain the dissociation constants of weak
      organic acids such as substituted benzoic and cinnamic acids in solution.
      Partition coefficient, supramolecular structure formation and stoichiometry,
      critical micelle concentration, and binding or association constant of a molecule
      with another molecule have all been measured by the HRS technique by us. We find
      that both the symmetry of the molecule and its concentration in the medium play
      an important role in finding new chemical applications of the technique.

PMID- 16610852
TI  - Hydrothermal synthesis of Zn2SnO4 nanorods in the diameter regime of sub-5 nm and
      their properties.
AB  - Single crystalline Zn(2)SnO(4) (ZTO) nanorods 2-4 nm in diameter and around 20 nm
      in length were successfully synthesized by a simple hydrothermal process with use
      of hydrazine hydrate as an alkaline mineralizer instead of NaOH or NH(3).H(2)O.
      By analyzing the UV-vis diffuse reflectance spectrum, the optical band gap (E(g))
      of the nanorods was found to be 3.87 eV, which indicates a blue shift of 0.27 eV
      from that of bulk ZTO (3.6 eV). In situ high-temperature X-ray diffraction was
      employed to study the thermal expansion coefficient and the variation of lattice
      parameter with temperature of the product. Furthermore, we discussed the chemical
      mechanism and key factors to the hydrothermal formation of the sub-5 nm ZTO
      nanorods.

PMID- 16610853
TI  - Hybrid polymer/zinc oxide photovoltaic devices with vertically oriented ZnO
      nanorods and an amphiphilic molecular interface layer.
AB  - We report on the effect of nanoparticle morphology and interfacial modification
      on the performance of hybrid polymer/zinc oxide photovoltaic devices. We compare
      structures consisting of poly-3-hexylthiophene (P3HT) polymer in contact with
      three different types of ZnO layer: a flat ZnO backing layer alone; vertically
      aligned ZnO nanorods on a ZnO backing layer; and ZnO nanoparticles on a ZnO
      backing layer. We use scanning electron microscopy, steady state and transient
      absorption spectroscopies, and photovoltaic device measurements to study the
      morphology, charge separation, recombination behavior and device performance of
      the three types of structures. We find that charge recombination in the
      structures containing vertically aligned ZnO nanorods is remarkably slow, with a
      half-life of several milliseconds, over 2 orders of magnitude slower than that
      for randomly oriented ZnO nanoparticles. A photovoltaic device based on the
      nanorod structure that has been treated with an amphiphilic dye before deposition
      of the P3HT polymer yields a power conversion efficiency over four times greater
      than that for a similar device based on the nanoparticle structure. The best ZnO
      nanorod:P3HT device yields a short circuit current density of 2 mAcm(-2) under
      AM1.5 illumination (100 mW cm(-2)) and a peak external quantum efficiency over
      14%, resulting in a power conversion efficiency of 0.20%.

PMID- 16610854
TI  - Theoretical and experimental investigation of morphology and temperature effects
      on adsorption of organic vapors in single-walled carbon nanotubes.
AB  - Hexane adsorption on single-walled carbon nanotube (SWNT) bundles is studied by
      both simulation and experimentally using a previously developed computer-aided
      methodology, which employed a smaller physisorbed probe molecule, nitrogen, to
      explore the porosity of nanotube samples. Configurational-bias grand canonical
      Monte Carlo simulation of hexane adsorption on localized sites of the bundles is
      carried out to predict adsorption on their external surface and in their internal
      sites. These localized isotherms are then combined into a global isotherm for a
      given sample by using knowledge of its tube-diameter distribution and structural
      parameters, such as the fraction of open-ended nanotubes and the external surface
      area of bundles in samples, which have been independently determined from the
      standard nitrogen adsorption isotherm. The near-perfect replication of
      experimental isotherms demonstrates the validity of our method for structural
      characterization of SWNT samples. The effect of temperature on adsorption is also
      studied and the simulation results are extrapolated to predict the limiting
      hexane adsorption capacity of the samples. The similarity between the hexane
      adsorption isotherms and those of other organic molecules demonstrates that the
      adsorption mechanisms explored here are not specific to hexane, and that the
      proposed methodology can be potentially applicable to other sorbates with equal
      success.

PMID- 16610855
TI  - Surface enhanced second harmonic generation from macrocycle, catenane, and
      rotaxane thin films: experiments and theory.
AB  - Surface enhanced second harmonic generation (SE SHG) experiments on molecular
      structures, macrocycles, catenanes, and rotaxanes, deposited as monolayers and
      multilayers by vacuum sublimation on silver, are reported. The measurements show
      that the molecules form ordered thin films, where the highest degree of order is
      observed in the case of macrocycle monolayers and the lowest in the case of
      rotaxane multilayers. The second harmonic generation activity is interpreted in
      terms of electric field induced second harmonic (EFISH) generation where the
      electric field is created by the substrate silver atoms. The measured second
      order nonlinear optical susceptibility for a rotaxane thin film is compared with
      that obtained by considering only EFISH contribution to SHG intensity. The
      electric field on the surface of a silver layer is calculated by using the
      Delphi4 program for structures obtained with TINKER molecular mechanics/dynamics
      simulations. An excellent agreement is observed between the calculated and the
      measured SHG susceptibilities.

PMID- 16610856
TI  - Highly fluorescent crystalline and liquid crystalline columnar phases of pyrene
      based structures.
AB  - A concept for highly ordered solid-state structures with bright fluorescence is
      proposed: liquid crystals based on tetraethynylpyrene chromophores, where the
      rigid core is functionalized with flexible, promesogenic alkoxy chains. The
      synthesis of this novel material is presented. The thermotropic properties are
      studied by means of differential scanning calorimetry (DSC), cross-polarized
      optical microscopy (POM), and X-ray diffraction. The mesogen possesses an
      enantiotropic Col(h) phase over a large temperature range before clearing. The
      material is highly fluorescent in solution and, most remarkably, in the condensed
      state, with a broad, strongly red shifted emission. Fluorescence quantum yields
      (Phi(F)) have been determined to be 70% in dichloromethane solution and 62% in
      the solid state. Concentration- and temperature-dependent absorption and emission
      studies as well as quantum-chemical calculations on isolated molecules and dimers
      are used to clarify the type of intermolecular interactions present as well as
      their influence on the fluorescence quantum yield and spectral properties of the
      material. The high luminescence efficiency in the solid state is ascribed to
      rotated chromophores, leading to an optically allowed lowest optical transition.

PMID- 16610857
TI  - Mechanism of oxidative shuttling for [2]rotaxane in a Stoddart-Heath molecular
      switch: density functional theory study with continuum-solvation model.
AB  - The central component of the programmable molecular switch demonstrated recently
      by Stoddart and Heath is [2]rotaxane, which consists of a cyclobis-(paraquat-p
      phenylene) ring-shaped shuttle [(CBPQT(4+))(PF(6)(-))(4)] encircling a finger and
      moving between two stations on the finger: tetrathiafulvalene (TTF) and 1,5
      dioxynaphthalene (DNP). We report here a quantum mechanics (QM) study of the
      mechanism by which movement of the ring (and in turn the on-off switching) is
      controlled by the oxidation-reduction process. We use B3LYP density functional
      theory to describe how oxidation of the [2]rotaxane components (in using Poisson
      Boltzmann continuum-solvation theory for acetonitrile solution) induces the
      motions associated with switching (translation of the ring). These calculations
      support the proposal that oxidation occurs on TTF, leading to repulsion between
      two positive charge centers (TTF(2+) and CBPQT(4+)) that drives the CBPQT(4+)
      ring from the TTF(2+) station toward the neutral DNP station. The theory also
      supports the experimental observation that the first and second oxidation
      potentials are nearly the same (separated by 0.09 eV in the QM). This excellent
      agreement between the QM and experiment suggests that QM can be useful in
      designing new systems.

PMID- 16610858
TI  - Graphitic encapsulation of catalyst particles in carbon nanotube production.
AB  - A new model is proposed for the encapsulation of catalyst metal particles by
      graphite layers that are obtained, for example, in low-temperature chemical vapor
      deposition production of carbon nanotubes (CNTs). In this model graphite layers
      are primarily formed from the dissolved carbon atoms in the metal-carbide
      particle when the particle cools. This mechanism is in good agreement with
      molecular dynamics simulations (which show that precipitated carbon atoms
      preferentially form graphite sheets instead of CNTs at low temperatures) and
      experimental results (e.g., encapsulated metal particles are found in low
      temperature zones and CNTs in high-temperature regions of production apparatus,
      very small catalyst particles are generally not encapsulated, and the ratio of
      the number of graphitic layers to the diameter of the catalyst particle is
      typically 0.25 nm(-1)).

PMID- 16610859
TI  - Structural and magnetic investigations for the doping effect of nonmagnetic
      impurity on the spin-Peierls-like transition in a quasi-one-dimensional magnet: 1
      (4'-nitrobenzyl)pyridinium bis(maleonitriledithiolato)nickelate.
AB  - A nonmagnetic compound, [NO(2)BzPy][Au(mnt)(2)] (NO(2)BzPy(+) = 1-(4'
      nitrobenzyl)pyridinium; mnt(2-) = maleonitriledithiolate), was synthesized and
      characterized structurally, which is isostructural with [NO(2)BzPy][Ni(mnt)(2)]
      that is a quasi-one-dimensional magnet and possesses a spin-Peierls-like
      transition with J = 192 K in the gapless state and spin energy gap = 738 K in the
      dimerization state, respectively. Further, ten nonmagnetic impurity doped
      compounds with a formula [NO(2)BzPy][Au(x)Ni(1-x)(mnt)(2)] (x = 0.01-0.73) were
      prepared and investigated by crystal structural determinations and magnetic
      susceptibility measurements. The nonmagnetic doping causes the suppression of the
      spin transition with an average rate of 221(12) K/percentage of dopant
      concentration. From the plots of chi(m)-T, the transition collapse (the
      characteristic of the transition is the sudden drop of chi(m) upon cooling, and
      the disappearance of this characteristic is considered as the criterion for the
      transition collapse) is estimated at around x > 0.27. In heavier doped system x =
      0.49, the spin gap vanishes and a gapless phase is achieved again.

PMID- 16610860
TI  - Anomalous narrowing of the structural relaxation dispersion of
      tris(dimethylsiloxy)phenylsilane at elevated pressures.
AB  - Broadband dielectric relaxation measurements of tris(dimethylsiloxy)phenylsilane
      were made at ambient pressure and at elevated pressures. The data show an
      anomalous behavior not previously seen in any other glass-formers; namely, the
      structural alpha-relaxation loss peak narrows with increasing pressure and
      temperature at constant peak frequency. Interpreted by the coupling model, the
      effect is due to reduction of intermolecular coupling at elevated pressures. This
      interpretation has support from the observed decrease of the separation between
      the alpha-relaxation and the Johari-Goldstein secondary relaxation, as well as
      the smaller steepness or "fragility" index m of the data obtained at 1.7 GPa than
      at ambient pressure.

PMID- 16610861
TI  - Selective functionalization of the Si(100) surface by a bifunctional alkynylamine
      molecule: density functional study of the switching adsorption linkage. 2.
AB  - The reaction of the bifunctional organic molecule 1-(dimethylamino)-2-propyne
      (DMAP) on the Si(100) surface has been investigated by density functional
      calculations employing a two-dimer cluster model. We found that, once in the
      physisorbed dative bonded well (-20.0 kcal mol(-1)), DMAP can proceed via a
      number of pathways, involving the formation of Si-C sigma bonds, which lead to
      thermodynamically more stable configurations. We first considered the
      cycloaddition of the CC triple bond, leading to a Si-C di-sigma bonded product (
      58.7 kcal mol(-1)), for which we computed an energy barrier of only 12.5 kcal
      mol(-1), consistently with the observed switching of DMAP adsorption linkage at
      300 K. We also explored the dissociative pathway involving the methylene C-H bond
      cleavage on the dative bonded DMAP, leading to three adsorption products with one
      (-57.3 kcal mol(-1)) and three Si-C sigma bonds (-58.7 and -60.6 kcal mol(-1)).
      The energy barrier for this pathway is computed 24.7 kcal mol(-1) and may
      therefore compete at temperature above 300 K with the reaction pathway involving
      the addition of the alkyne unit.

PMID- 16610862
TI  - Investigation of corannulene for molecular hydrogen storage via computational
      chemistry and experimentation.
AB  - Molecular simulations for hydrogen physisorption with corannulene molecules
      arranged according to their crystal structure result in good agreement with the
      weight-percent hydrogen stored as determined experimentally employing a 3-g
      sample of highly crystalline corannulene at ambient temperatures and 72 bar of
      pressure. Calculated enthalpies of adsorption for corannulene/hydrogen molecular
      systems obtained from ab initio calculations which take into account electron
      correlation via second-order Moller-Plesset perturbation theory are in good
      agreement with literature experimental enthalpies of adsorption for activated
      carbons interacting with molecular hydrogen. Ab initio results also show that
      corannulene molecules arranged in a sandwich structure are important for
      approximately doubling the binding energy of corannulene interacting with
      molecular hydrogen through a cooperative interaction. To test the effects of
      finite temperatures and pressures, stack arrays were used as input for molecular
      dynamics simulations and indicate that physisorption mechanisms including van der
      Waals forces and dipole-induced dipole interactions may yield enhanced adsorption
      capacity in relation to other carbon-based materials. These results will be
      instrumental in identifying interlayer separations of an array of corannulene or
      related molecules that may provide a high weight percent of physisorbed hydrogen.

PMID- 16610863
TI  - Formation of nonclassical carbonyls of Au3+ in zeolite NaY: characterization by
      infrared spectroscopy.
AB  - Adsorption of CO on gold supported in zeolite NaY at 85 K led to the formation of
      (i) various carbonyls and isocarbonyls typical of the zeolite and (ii) carbonyls
      formed at cationic gold sites (observed in the 2186-2171 cm(-1) region). Analysis
      of the behavior of the bands allows their assignment to carbonyls of Au(3+) ions.
      At temperatures higher than 220 K, CO adsorption led to the formation of a new
      type of Au(3+)-CO species (2207 cm(-1)). Once formed, these complexes could be
      transformed into the dicarbonyls Au(3+)(CO)(2) when the sample was cooled to 85 K
      in the presence of CO. The results are explained by migration of Au(3+) ions to
      more accessible positions within the zeolite at increasing temperatures. When a
      CO molecule is already adsorbed, it stabilizes the Au(3+) ion in the new
      position, and a second CO molecule can be coordinated, thus forming a geminal
      species. These results are the first evidence of Au(3+)(CO)(2) complexes.

PMID- 16610864
TI  - X-shaped oligothiophenes as a new class of electron donors for bulk
      heterojunction solar cells.
AB  - Four X-shaped oligothiophenes with different conjugation length were investigated
      as novel electron donors in single-layer bulk-heterojunction solar cells. The UV
      vis absorption spectra of blends of compounds 1-4 with 1-(3
      methoxycarbonyl)propyl-1-phenyl[6,6]C(61) show a remarkably red shift and
      broadening with increasing thiophene number at each of the four branches. The
      performance of the photovoltaic cells varied significantly with molecular
      structures of the four oligothiophenes. Conversion efficiencies increased from
      0.008% to 0.8% with changing the electron donors from 1 to 4. The maximum
      incident photon-to-current conversion efficiency of the device based on 4 reaches
      31.6%, much higher than those of three other compounds 1-3. Remarkable
      improvement of the device performance was achieved with increasing the
      substituted thiophene number. The results show that the photovoltaic effect is
      dependent on the structural characteristics and the film forming abilities of the
      X-shaped thiophenes.

PMID- 16610865
TI  - Syntheses and characterization of lithium alkyl mono- and dicarbonates as
      components of surface films in Li-ion batteries.
AB  - A homologous series of lithium alkyl mono- and dicarbonate salts was synthesized
      as model reference compounds for the frequently proposed components constituting
      the electrolyte/electrode interface in Li-ion batteries. The physicochemical
      characterization of these reference compounds in the bulk state using thermal
      analyses and X-ray photoelectron, nuclear magnetic resonance, and Fourier
      transform infrared spectroscopies establishes a reliable database of comparison
      for the studies on the surface chemistry of electrodes harvested from Li-ion
      cells.

PMID- 16610866
TI  - Density-controlled growth of aligned ZnO nanowires sharing a common contact: a
      simple, low-cost, and mask-free technique for large-scale applications.
AB  - An effective, low cost, simple, and mask-free pathway is demonstrated for
      achieving density control of the aligned ZnO nanowires grown for large-scale
      applications. By a slight variation of the thickness of the thermally evaporated
      gold catalyst film, a significant change in the density of aligned ZnO nanowires
      has been controlled. The growth processes of the nanowires on an Al(0.5)Ga(0.5)N
      substrate has been studied based on the wetting behavior of gold catalyst with or
      without source vapor, and the results classify the growth processes into three
      categories: separated dots initiated growth, continuous layer initiated growth,
      and scattered particle initiated growth. This study presents an approach for
      growing aligned nanowire arrays on a ceramic substrate with the simultaneous
      formation of a continuous conducting electrode at the roots, which is important
      for device applications, such as field emission.

PMID- 16610867
TI  - Particle size control in dendrimer-derived supported ruthenium catalysts.
AB  - A high-resolution transmission electron microscopy (HRTEM) investigation of a
      family of supported Ru catalysts prepared from Ru hydroxyl-terminated
      poly(amidoamine) dendrimer-metal nanocomposite (DMN) precursors has been
      conducted. Ru particle sizes observed following deposition of DMNs on a HRTEM
      grid can be controlled within a 0.9-1.4 nm range depending on the metal-to
      dendrimer molar ratio. The average particle size in this case correlates well
      with the theoretically predicted particle size from the molar loading of Ru in
      the dendrimer. Upon impregnation of Ru-DMNs on Al(2)O(3) and subsequent thermal
      removal of the dendrimer via reduction at 300 degrees C, significant sintering of
      the Ru particles was observed. Nevertheless, the resulting supported Ru particles
      maintained a narrow particle size distribution and average particle size below
      2.5 nm. These particle sizes no longer correlate with the metal-to-dendrimer
      molar ratio but do correlate with the metal-to-dendrimer weight ratio, suggesting
      that the dendrimer may be acting as a "sintering-control" agent on the catalyst
      surface. This process is not affected by the surface area of the support, since
      almost identical particle size distributions were obtained on three different
      commercial supports.

PMID- 16610868
TI  - Electrofluorescence of MEH-PPV and its oligomers: evidence for field-induced
      fluorescence quenching of single chains.
AB  - Electrofluorescence (Stark) spectroscopy has been used to measure the trace of
      the change in polarizability (trDeltaalpha) and the absolute value of the change
      in dipole moment (|Deltamu|) of the electroluminescent polymer poly[2-methoxy,5
      (2'-ethyl-hexoxy)-1,4-phenylene vinylene] (MEH-PPV) and several model oligomers
      in solvent glass matrixes. From electrofluorescence, the measured values of
      trDeltaalpha increase from 500 +/- 60 A(3) in OPPV-5 to 2000 +/- 200 A(3) in MEH
      PPV. The good agreement found between these values and those measured by
      electroabsorption suggests the electronic properties do not differ strongly
      between absorption and emission, in contrast to earlier predictions. Evidence of
      electric-field-induced fluorescence quenching of MEH-PPV in dilute solvent
      glasses was found. When normalized to the square of the applied electric field,
      the magnitude of quench is comparable to that reported in the literature for thin
      films of MEH-PPV. In addition, fluorescence quenching was also observed in the
      oligomers with a magnitude that increases with increasing chain length. By using
      the values of trDeltaalpha measured by electrofluorescence, a model is developed
      to qualitatively explain the chain length dependence to the fluorescence quench
      observed in the oligomers as a function of exciton delocalization along the
      oligomer backbone. Various explanations for the origin of this quenching behavior
      and its chain length dependence are considered.

PMID- 16610869
TI  - Nanostructure of silver metal produced photocatalytically in TiO2 films and the
      mechanism of the resulting photochromic behavior.
AB  - The optical activity of composite films created by the photocatalytic reduction
      of silver or gold ions in TiO(2) upon irradiation by UV light has up to now been
      discussed in terms of the formation and light-induced destruction of distinct
      nanoparticles molded inside the porous nanocrystalline film. We present results
      from classical light scattering calculations and a logical analysis of
      experimental observations to add detail to the mechanism. As opposed to large,
      solid metal nanoparticles, coatings and small particles in heterogeneous external
      dielectric environments account for observations such as the broad optical
      spectrum and multiwavelength photochromic responses. For some steps of the
      photochromic process, we propose that visible light permits an equilibrium
      promoting the growth of small metal features or suspended particles. We use a new
      expression for the restricted path length in our size-dependent broadening
      corrections of metal shells and discuss this briefly. We conclude by discussing
      the consequence of plasmon absorption in the proximity of the electronically
      active TiO(2) surrounding matrix, leading to mass transfer and shape change of
      the metal and photochromic properties of the film.

PMID- 16610870
TI  - Fabrication of copper hydroxyphosphate with complex architectures.
AB  - Copper hydroxyphosphate [Cu(2)(OH)PO(4)] with complex architectures has been
      synthesized through a simple and mild hydrothermal route in the absence of any
      external inorganic additives or organic structure-directing templates. Powder X
      ray diffraction, scanning electron microscopy, and Fourier transform infrared
      spectrometry are used to characterize various properties of the obtained samples.
      Single-crystals, twinned-crystals, and various novel architectures of copper
      hydroxyphosphate can be constructed through a careful control of synthetic
      parameters, such as the molar ratio of initial reagents, reagent concentration,
      reaction time, and temperature. On the basis of structure and chemical bond
      analysis, copper hydroxyphosphate crystals tend to grow along the c-axis and have
      a rotation twinned-crystal growth habit, which is essential for the formation of
      various complex architectures. The current approach provides a facile strategy to
      synthesize copper hydroxyphosphate crystals with unique morphologies and complex
      architectures, which may be applicable to the synthesis of other inorganic
      materials.

PMID- 16610871
TI  - Structure of silica xerogels synthesized with organoalkoxysilane co-reactants
      hints at multiple phase separation.
AB  - The microstructure of hybrid silica xerogels synthesized by the base-catalyzed
      polymerization of tetraethoxysilane (TEOS) in ethanol in the presence of 3
      aminopropyltriethoxysilane (AES) and of 3-(2
      aminoethylamino)propyltrimethoxysilane (EDAS) as co-reactants, and dried in
      subcritical conditions, is analyzed. A thorough structural characterization of
      the samples is performed combining nitrogen adsorption, small-angle X-ray
      scattering (SAXS), and transmission electron microscopy coupled with digital
      image analysis. The use of these methods shows that, for both co-reactants, the
      xerogels are made of macropores supported by filaments, with each filament being
      formed of smaller structures. The quantitative impact of the additive on each
      structural level is assessed. The data are compared with a previous time-resolved
      SAXS study conducted during the formation of the gels (J. Phys. Chem. B 2004,
      108, 8983-8991). The results are analyzed in the framework of a double phase
      separation model.

PMID- 16610872
TI  - Analysis of conformational polymorphism in pharmaceutical solids using solid
      state NMR and electronic structure calculations.
AB  - A detailed analysis of molecular structure in three polymorphic forms of 5-methyl
      2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile is made using a combination of
      multidimensional solid-state NMR (SSNMR) experiments and molecular modeling via
      electronic structure calculations. These compounds, collectively referred to as
      ROY because of their red, orange, and yellow colors, share a similar molecular
      structure with the exception of the dihedral angle between the phenyl and
      thiophene rings. The ROY materials make it possible to study the influence of
      nearly a single degree of freedom on the associated NMR spectra. Using the 2D
      PASS (Antzutkin et al. J. Magn. Reson. A 1995, 115, 7) experiment, spectral
      editing techniques, and DFT-based calculations of the local fields, an analysis
      is made of the sensitivity of all carbon and nitrogen sites to changing molecular
      conformation. Chemical shift and dipolar coupling information obtained from these
      experiments vary noticeably between forms and are subsequently used to
      quantitatively determine aspects of molecular structure in these materials,
      including the coplanar angle between the phenyl and thiophene rings. The
      influence of motion on the methyl and nitro chemical shifts is also investigated.
      The accuracy of the information obtained from local field analysis and the model
      structure calculation demonstrates the capabilities of SSNMR as a quantitative
      structural method.

PMID- 16610874
TI  - How to adapt Scatchard plot for graphically addressing cooperativity in
      multicomponent self-assemblies.
AB  - A graphical method has been developed for the reliable detection of cooperativity
      in polymetallic complexes involving intra- and intermolecular complexation
      processes. The method relies on the determination of the partial occupancy
      r(AL)n, which represents the average number of metals bound per preassembled
      receptor AL(n) made up of n ligands bound to a linker A. We observe nonlinear,
      i.e., nonstatistical, Scatchard-like plots (r(AL)n/[M] vs r(AL)n) for metal
      binding in double-stranded helicates. The present concept is extended to a
      virtual, pre-organized receptor L(n), in which no specific linker is involved.
      Applications to several polymetallic helicates reveal the presence of negatively
      cooperative processes attributed mainly to intermetallic repulsions, in agreement
      with recent thermodynamic models.

PMID- 16610873
TI  - Studies of photoinduced electron transfer and energy migration in a conjugated
      polymer system for fluorescence "turn-on" chemosensor applications.
AB  - A series of poly[p-(phenyleneethynylene)-alt-(thienyleneethynylene)] (PPETE)
      polymers with variable percent loadings of the N,N,N'-trimethylethylenediamino
      group on the polymer backbone were synthesized and fully characterized.
      Photophysical studies show that changes in the loading of the amino group
      receptor on the backbone do not affect the polymer electronic structure in either
      the ground or excited states. The fluorescence quantum yields were found to be
      directly related to the loading of the amino groups and can be modeled by a Stern
      Volmer type relationship. Photophysical studies related the total quenching
      efficiency to the inherent rate of photoinduced electron transfer (PET), the
      lifetime of the exciton, the rate of excitation energy migration along the
      polymer backbone, and the total loading of the receptor on the polymer. The role
      of the loading dependence on the application of these polymers as fluorescence
      "turn-on" sensors for toxic metal cations in dilute solution was also studied.
      Results showed that the fluorescence enhancement upon binding various cations was
      maintained even when the amino receptor loading along the polymer backbone was
      reduced.

PMID- 16610875
TI  - The influence of pressure on the lower critical solution temperature miscibility
      behavior of aqueous solutions of poly(vinyl methyl ether) and the relation to the
      compositional curvature of the volume of mixing.
AB  - In mixtures of PVME and water, the influence of pressure on the LCST miscibility
      gap is determined covering the whole composition range and pressures from
      atmospheric pressure up to 900 MPa. The cloud point curve at atmospheric pressure
      has the characteristic bimodal shape in agreement with literature data. Upon
      increasing pressure the cloud point curve at the low concentration side decreases
      with pressure, whereas at the high concentrations the cloud point curve increases
      with pressure. The overall influence of pressure results in a less pronounced
      bimodality and ultimately the bimodal shape disappears. In addition to the
      pressure dependence of the miscibility behavior, the density of mixtures of water
      and PVME are determined at atmospheric pressure. The experimental excess specific
      volumes are negative for all measured compositions, but the compositional
      curvature varies with composition. The curvature of the excess specific volume is
      positive for the higher concentrations but it is negative in the lower
      composition range. The density measurements are linked to the pressure dependence
      of the LCST miscibility behavior using exact thermodynamic relationships. The
      excess specific volume and miscibility results are shown to be in good agreement.
      Moreover, it is shown that the Clapeyron equation, which is exact for pure
      components and also frequently assumed to apply to mixtures, is not valid in the
      system PVME/water. The system PVME/water is an example where the usual
      approximation of one-to-one correspondence between curvature and excess volume
      does not apply. Finally, the molecular origins for the observed excess volume and
      miscibility behavior are briefly discussed from theoretical and molecular
      simulation points of view.

PMID- 16610876
TI  - Synthesis and characterization of long perylenediimide polymer fibers: from bulk
      to the single-molecule level.
AB  - The synthesis and characterization of perylenediimide polyisocyanides is
      reported. In addition to short oligomers, our synthetic approach results in the
      formation of extremely long, well-defined, and rigid perylenediimide polymers.
      Ordering and close-packing of the chromophores in these long polymers is
      guaranteed by attachment to a polyisocyanide backbone with amino acid side
      chains. Hydrogen bonding interactions between those groups stabilize and rigidify
      the helical polymer structure. The rodlike nature of the synthesized long
      perylenediimide pendant polyisocyanides as well as the helical arrangement of the
      chromophores is demonstrated by means of atomic force microscopy. Remarkably,
      polymer fibers up to 1 mum in length have been visualized, containing several
      thousands of perylenediimide molecules. Circular dichroism spectroscopy reveals
      the chiral organization of the chromophore units in the polymer, whereas
      absorption and emission measurements prove the occurrence of excited-state
      interactions between those moieties due to the close packing of the chromophore
      groups. However, an intricate optical behavior is encountered in bulk as a result
      of the coexistence of short oligomers and long polymers of perylenediimide, a
      situation subsequently uncovered by means of single-molecule experiments.
      Individual long helical perylenediimide polyisocyanides exhibit a typical red
      shifted fluorescence spectrum, which, together with depolarized emission
      continuously decreasing in time, demonstrate that fluorescence arises from
      multiple excimer-like species in the polymer. Upon continuous irradiation of
      these long polymers, a fast decay in fluorescence lifetime is observed, a
      situation explained by photoinduced creation of quenching sites. Radical/ion
      formation by intramolecular electron transfer between close-by perylenediimide
      moieties is the most probable mechanism for this process. Appropriate control of
      the electron-transfer process might open the possibility of applying these
      polymers as perylenediimide-based supramolecular nanowires.

PMID- 16610877
TI  - Arrangement and mobility of water in vermiculite hydrates followed by 1H NMR
      spectroscopy.
AB  - The arrangement of water molecules in one- and two-layer hydrates of high-charged
      vermiculites, saturated with alkaline (Li(+), Na(+)) and alkali-earth (Mg(2+),
      Ca(2+), Ba(2+)) cations, has been analyzed with (1)H NMR spectroscopy. Two
      different orientations for water molecules have been found, depending on the
      hydration state and the sites occupied by interlayer cations. As the amount of
      water increases, hydrogen bond interactions between water molecules increase at
      expenses of water-silicate interactions. This interaction favors water mobility
      in vermiculites. A comparison of the temperature dependence of relaxation times
      T(1) and T(2) for one and two-layer hydrates of Na-vermiculite shows that the
      rotations of water molecules around C(2)-axes and that of cation hydration shells
      around the c-axis is favored in the two-layer hydrate. In both hydrates, the
      anisotropic diffusion of water takes place at room temperature, preserving the
      orientation of water molecules relative to the silicate layers. Information
      obtained by NMR spectroscopy is compatible with that deduced by infrared
      spectroscopy and with structural studies carried out with X-ray and neutron
      diffraction techniques on single-crystals of vermiculite.

PMID- 16610878
TI  - A theoretical study on growth patterns of Ni-doped germanium clusters.
AB  - Ni-doped germanium clusters have been systematically investigated by using the
      density functional approach. The growth-pattern behaviors, stabilities, charge
      transfer, and polarities of these clusters are discussed in detail. Obviously
      different growth patterns appear between small-sized Ni-doped germanium clusters
      and middle- or larger-sized Ni-doped germanium clusters. The Ni-convex or
      substituted Ge(n) frames for small-sized clusters as well as Ni-concaved or
      encapsulated Ge(n) frames for middle- or large-sized clusters are dominant growth
      patterns. The calculated fragmentation energies manifest that the magic numbers
      of stabilities are 5, 8, 10, and 13 for Ni-doped germanium clusters; the obtained
      relative stabilities exhibit that the Ni-encapsulated Ge(10) cluster is the most
      stable species of all different-sized clusters, which is in good agreement with
      available experimental observations of CoGe(10)(-). Natural population analysis
      shows that different charge-transfer phenomena depend on the sizes of the Ni
      doped Ge(n) clusters. Additionally, the properties of frontier orbitals and the
      polarities of Ni-doped Ge(n) clusters are also discussed.

PMID- 16610879
TI  - Synthesis and structure-activity relationship exploration of carbon-supported
      PtRuNi nanocomposite as a CO-tolerant electrocatalyst for proton exchange
      membrane fuel cells.
AB  - A carbon-supported PtRuNi nanocomposite is synthesized via a microwave-irradiated
      polyol plus annealing synthesis strategy. The catalyst is characterized by
      transmission electron microscopy, powder X-ray diffraction, energy dispersive
      spectroscopy, and X-ray photoelectron spectroscopy. The data are discussed with
      respect to those for the carbon-supported PtRu nanocomposite prepared following
      the same way. The characterizations show that the inclusion of Ni in the PtRu
      system has only a small effect on the particle size, the structure, and the
      compositional homogeneity. CO-stripping voltammetry and measurements on the
      single proton exchange membrane fuel cells show that the PtRuNi/C catalyst has an
      improved activity for CO(ads) electro-oxidation. An accelerated durability test
      on the catalyst exhibits insignificant loss of activity in acidic media. On the
      basis of the exploration of the structure-activity relationship, a mechanism for
      the improved performance of the catalyst is proposed. It is suggested that the
      improved CO-tolerant performance of the PtRuNi/C nanocomposite should be related
      to the hydrogen spillover on the catalyst surface, the enhanced oxidation of
      CO(ads) by nickel hydroxides, and the high proton and electronic conductivity of
      the hydroxides. The nickel hydroxide passivated surface and/or anchoring of
      metallic nickel in the platinum lattice may contribute to the durability of the
      catalyst in acid solution.

PMID- 16610880
TI  - Aqueous solvation dynamics at metal oxide surfaces.
AB  - Broadband transient absorption (TA) spectroscopy, three-pulse photon echo peak
      shift (3PEPS), and anisotropy decay measurements were used to study the solvation
      dynamics in bulk water and interfacial water at ZrO(2) surfaces, using Eosin Y as
      a probe. The 3PEPS results show a multiexponential behavior with two
      subpicosecond components that are similar in bulk and interfacial water, while a
      third component of several picoseconds is significantly lengthened at the
      interface. The bandwidth correlation function from TA spectra exhibits the same
      behavior, and the TA spectra are well reproduced using the doorway-window picture
      with the time constants from PEPS. Our results suggest that interfacial water is
      restricted to a thickness of less than 5 A. Also the high-frequency collective
      dynamics of water does not seem to be affected by the interface. On the other
      hand, the increase of the third component may point to a slowing down of
      diffusional motion at the interface, although other effects, may play a role,
      which are discussed.

PMID- 16610881
TI  - Nb2O5 "pathway effect" on hydrogen sorption in Mg.
AB  - In the present work we investigate the hydrogen sorption mechanism in a
      MgH(2)/Nb(2)O(5) composite and analyze why Nb(2)O(5) could strongly improve
      hydrogen sorption kinetics in magnesium. Hereby we make use of the fact that
      Nb(2)O(5) nanoparticles are able to reduce the milling time significantly with
      the achievement of excellent sorption kinetics, and can so exclude effects
      occurring at long-term milling that make difficult the study of the mechanism. On
      the basis of extensive chemical, crystalline, and microstructural
      characterization of the MgH(2)/Nb(2)O(5) nanopowder system, a "pathway model" is
      proposed, which explains the kinetic hydrogen sorption improvement by a formation
      of pathways of niobium oxide species with lower oxidation state that facilitate
      the hydrogen transport into the sample. This mechanism is shown to be supported
      by additional oxidation experiments, which indicate increased oxygen diffusion
      through these pathways.

PMID- 16610882
TI  - Dependence of copper species on the nature of the support for dispersed CuO
      catalysts.
AB  - Copper catalysts prepared by chemisorption-hydrolysis technique over silica
      (Cu/Si) and silica-alumina (Cu/SiAl) supports were studied to understand the role
      of the support on the nature and surface properties of the copper species
      stabilized on their surfaces. The morphological and surface properties of the
      copper phases have been characterized by complementary techniques, such as HRTEM,
      EXAFS-XANES, EPR, XPS, and FTIR. For the FTIR investigation, molecular probes (CO
      and NO) were also adsorbed on the surfaces to test the reactivity of the copper
      species. Moreover, the catalytic performances of the two catalysts have been
      compared in the HC-SCR reaction (NO reduction by C(2)H(4)) performed in highly
      oxidant conditions. The superior activity and selectivity of the supported silica
      alumina catalyst with respect to that supported on silica could be related with
      the different nature of the copper species stabilized on the two supports, as
      emerged from the results obtained from the spectroscopic investigations. Small
      and well-dispersed CuO particles were present on silica, whereas isolated copper
      ions predominated on silica-alumina, likely in regions rich in alumina that made
      some exchangeable sites available, as indicated by FTIR spectra of adsorbed CO.
      The less positive global charge of copper species on Cu/SiAl than in Cu/Si has
      been confirmed by EPR, XPS, and EXAFS-XANES analyses.

PMID- 16610883
TI  - In situ study of the growth kinetics of individual island electrodeposition of
      copper.
AB  - The growth kinetics for individual islands during electrodeposition of copper
      have been studied using in situ transmission electron microscopy. We show that
      for sufficiently large overpotentials, the growth kinetics approach the rate laws
      expected for diffusion-limited growth of hemispherical islands, characterized by
      two distinct regimes. At short times, the island growth exponent is 0.5 as
      expected for diffusion-limited growth of uncoupled hemispherical islands, while
      at longer times, the growth exponent approaches 1/6 as expected for planar
      diffusion to the growing islands. These results provide the first direct
      measurements of the growth of individual islands during electrochemical
      deposition. However, quantitative comparison with rate laws shows that the island
      radii are smaller than predicted and the island densities are much larger than
      predicted, and we suggest that this is related to adatom formation and surface
      diffusion, processes which are not included in conventional growth models.

PMID- 16610884
TI  - Metal particle growth during glucose hydrogenation over Ru/SiO2 evaluated by X
      ray absorption spectroscopy and electron microscopy.
AB  - Biorenewable resources such as carbohydrates are considered alternative
      feedstocks for oxygenated chemicals. This work investigates the stability of
      silica-supported Ru catalysts in the aqueous phase conversion of glucose to
      sorbitol. In situ X-ray absorption spectroscopy at the Ru K edge revealed that
      air-exposed silica-supported Ru was in an oxidized state but was subsequently
      reduced in aqueous solutions saturated with 40 bar H(2) at 373 K. Furthermore,
      exposure to aqueous phase conditions resulted in the sintering of Ru particles on
      the silica surface. However, the presence of glucose in the aqueous phase
      stabilized the growth of the Ru particles. Batchwise hydrogenation of glucose at
      373 K and 80 bar H(2) over a Ru/SiO(2) (2.67 wt %) catalyst is nearly 100%
      selective to sugar alcohol with an average turnover frequency of 0.21 +/- 0.04 s(
      1). The hydrogenation reaction was not mass transfer limited according to the
      Madon-Boudart criterion.

PMID- 16610885
TI  - A novel carbon electrode material for highly improved EDLC performance.
AB  - Porous materials, developed by grafting functional groups through chemical
      surface modification with a surfactant, represent an innovative concept in energy
      storage. This work reports, in detail, the first practical realization of a novel
      carbon electrode based on grafting of vinyltrimethoxysilane (vtmos) functional
      group for energy storage in electric double layer capacitor (EDLC). Surface
      modification with surfactant vtmos enhances the hydrophobisation of activated
      carbon and the affinity toward propylene carbonate (PC) solvent, which improves
      the wettability of activated carbon in the electrolyte solution based on PC
      solvent, resulting in not only a lower resistance to the transport of electrolyte
      ions within micropores of activated carbon but also more usable surface area for
      the formation of electric double layer, and accordingly, higher specific
      capacitance, energy density, and power capability available from the capacitor
      based on modified carbon. Especially, the effects from surface modification
      become superior at higher discharge rate, at which much better EDLC performance
      (i.e., much higher energy density and power capability) has been achieved by the
      modified carbon, suggesting that the modified carbon is a novel and very
      promising electrode material of EDLC for large current applications where both
      high energy density and power capability are required.

PMID- 16610886
TI  - Time-resolved infrared spectroscopy of K3Ta3B2O12 photocatalysts for water
      splitting.
AB  - Electrons photoexcited in K(3)Ta(3)B(2)O(12), an efficient photocatalyst for the
      water-splitting reaction driven by ultraviolet light, were observed using time
      resolved IR absorption spectroscopy with microsecond resolution. When the
      catalyst was irradiated with 266 nm light pulses, a structureless absorption
      appeared at 3000-1500 cm(-1). The absorption was assigned to the optical
      transition of electrons that were band gap-excited and then trapped in mid-gap
      states. The absorbance decayed with a time delay because of the electron-hole
      recombination. The rate of recombination in an argon atmosphere was sensitive to
      the composition of the starting material used in the catalyst preparation. The
      electron decay was accelerated by exposing the catalyst to water vapor. The
      degree of acceleration was qualitatively correlated with the H(2) production rate
      observed during steady-state light irradiation.

PMID- 16610887
TI  - Interpretation of the experimental data on the reduction reaction of NO by CO on
      rhodium by Monte Carlo simulations and by solving the kinetic equations of the
      reaction mechanism.
AB  - Some mechanisms of the reduction reaction of NO by CO on rhodium are analyzed and
      discussed, solving the kinetics equations and using Monte Carlo simulations, in
      terms of its ability to interpret the recent experiments of Zaera et al., who
      used a molecular beam method to study experimentally the kinetics of the
      reaction. Critical use is also made of the information on rate constants
      available for this system in the literature. Uniform catalytic surfaces and the
      statistical incipient percolation cluster (IPC) fractal are considered in the
      simulations.

PMID- 16610888
TI  - Molecule-molecule versus molecule-substrate interactions in the assembly of
      oligothiophenes at surfaces.
AB  - In this paper we present a joint experimental and theoretical approach for the
      study of the assembly of end-substituted oligothiophenes at surfaces with
      different polarities (i.e., mica vs graphite). Scanning probe microscopy studies
      of (sub)monolayer deposits show various types of structures (one-dimensional
      fibrils, two-dimensional regular layers, and monolayers), depending on the nature
      of the end groups and the substrate. Using molecular modeling with an atomistic
      approach, we focus on the interplay between the molecule-molecule (and segment
      segment) interactions and the molecule-substrate interactions and their influence
      on the observed morphologies and the stacking geometry. Such information is
      relevant for controlling the structural order in thin layers of thiophene
      oligomers for use in field-effect transistor applications, for example, by
      modifying the nature of dielectric material over which those compounds are
      deposited.

PMID- 16610889
TI  - An ab initio periodic study of NiO supported at the Pd(100) surface. Part 1: The
      perfect epitaxial monolayer.
AB  - The epitaxial monolayer of NiO on Pd(100) has been theoretically simulated using
      a hybrid-exchange GGA-DFT Hamiltonian and a slab model, periodic in two
      dimensions. This "perfect" system is an essential reference for the simulation of
      nonstoichiometric two-dimensional phases which are formed during the deposition
      of nickel on palladium in the presence of oxygen. The adequacy of the
      computational procedure is discussed, especially as concerns the use of a thermal
      smearing technique which has been adopted to improve the convergence properties
      of the SCF procedure and to prevent the onset of nonphysical spin-polarized
      solutions. The equilibrium configuration corresponds to antiferromagnetic order
      in the overlayer, with oxygens on top of the surface Pd atoms; the ad-film is
      slightly corrugated with Ni closer to the surface by 0.1 A with respect to O. The
      interaction energy is quite small, 0.20 eV/NiO unit (about 5 kcal mol(-1));
      correspondingly, the electronic and magnetic properties of the Pd slab and the
      isolated NiO monolayer are only marginally affected by the interaction.

PMID- 16610890
TI  - An ab initio periodic study of NiO supported at the Pd(100) surface. Part 2: The
      nonstoichiometric Ni3O4 phase.
AB  - The present computational study describes the structure and properties of a
      substoichiometric 2D monatomic in the height phase of nickel oxide, c(4 x 2)
      Ni(3)O(4), which has been newly found to epitaxially grow under special
      deposition conditions on the (100) face of palladium. A slab model is adopted
      where palladium is simulated by a thin film covered on both sides by epilayers,
      in combination with a DFT hybrid-exchange Hamiltonian; to make convergence of the
      SCF procedure easier, a thermal smearing technique is used, whose consequences on
      the results are critically analyzed. Three adsorbed systems are considered and
      characterized: (i) RH, that is, the c(4 x 2)-Ni(3)O(4) phase with a rhombic
      distribution of Ni vacancies, as is experimentally observed; SQ, or p(2 x 2)
      Ni(3)O(4), which differs from the previous one for a square, instead of a rhombic
      distribution of vacancies; (iii) OX, or p(2 x 2)-O, that is, a surface oxidized
      phase of Pd(100) which is believed to be the precursor for the formation of RH.
      For a better understanding of the interaction of the metal with the adlayers, the
      isolated substoichiometric oxides, i-RH and i-SQ, have also been studied. It is
      shown that RH is more stable than SQ by a few tenths of electronvolts per
      Ni(3)O(4) unit, which justifies its preferential formation and that the surface
      reaction, OX + 3NiO(ads) --> RH, is thermodynamically possible. Special attention
      has been devoted to characterize RH from an energetic, geometric, electronic, and
      magnetic viewpoint. The strong bond which is formed between surface Pd and O ions
      in the adlayer is responsible for some peculiar aspects of the electronic and
      magnetic structures of that phase.

PMID- 16610891
TI  - Photophysical properties of dioxolane-substituted pentacene derivatives dispersed
      in tris(quinolin-8-olato)aluminum(III).
AB  - Two novel dioxolane-substituted pentacene derivatives, namely, 6,14-bis
      (triisopropylsilylethynyl)-1,3,9,11-tetraoxa-dicyclopenta[b,m]pentacene (TP-5)
      and 2,2,10,10-tetraethyl-6,14-bis-(triisopropylsilylethynyl)-1,3,9,11-tetraoxa
      dicyclopenta[b,m]pentacene (EtTP-5), have been synthesized and spectroscopically
      characterized. Here, we examine the steady-state and time-resolved
      photoluminescence (PL) of solid-state composite films containing these pentacene
      derivatives dispersed in tris(quinolin-8-olato)aluminum(III) (Alq(3)). The films
      show narrow red emission and high absolute photoluminescence quantum yields
      (phi(PL) = 59% and 76% for films containing approximately 0.25 mol % TP-5 and
      EtTP-5, respectively). The Forster transfer radius for both guest-host systems is
      estimated to be approximately 33 A. The TP-5/Alq(3) thin films show a marked
      decrease in phi(PL) with increasing guest molecule concentrations, accompanied by
      dramatic changes in the PL spectra, suggesting that intermolecular interactions
      between pentacene molecules result in the formation of weakly radiative
      aggregates. In contrast, a lesser degree of fluorescence quenching is observed
      for EtTP-5/Alq(3) films. The measured fluorescence lifetimes of TP-5 and EtTP-5
      are similar (approximately 18 ns) at low concentrations but deviate at higher
      concentrations as aggregation begins to play a role in the TP-5/Alq(3) films. The
      onset of aggregation in EtTP-5/Alq(3) films occurs at higher guest molecule
      concentrations (>1.00 mol %). The addition of ethyl groups on the terminal
      dioxolane rings leads to an increase in the intermolecular spacing in the solid,
      thereby reducing the tendency for pi-pi molecular stacking and aggregation.

PMID- 16610892
TI  - Chemical reactions and adsorption geometries of pyrrole on Ge(100).
AB  - The adsorption structures of pyrrole (C(4)H(5)N) on a Ge(100) surface at various
      coverages have been investigated with both scanning tunneling microscopy (STM)
      and ab initio density-functional theory (DFT) calculations. Three distinct
      features are observed in the STM images at low coverages. The comparison of the
      STM images with the simulation reveals that the most dominant flowerlike feature
      with a dark side is that the adsorbed pyrrole molecules with H dissociated form
      bridges between two down Ge atoms of neighboring Ge dimer rows through N-Ge
      bonding and beta-carbon-Ge interaction. The flowerlike feature without a dark
      side is also observed as a minority, which is identified as nearly the same
      structure as the most dominant one where a dissociated H is out of the feature.
      The third feature showing bright protrusions may be due to a C- and N-end-on (CN)
      configuration, where the pyrrole molecule is located on one dimer row. At higher
      coverages, the number of localized configurations increases.

PMID- 16610893
TI  - Evidence for an influence of local dipole excitations in thermal desorption.
AB  - Ferroelectric crystalline copolymer films of vinylidene fluoride with
      trifluoroethylene (70%:30%) strongly interact with the dipoles of adsorbed and
      absorbed water molecules. This interaction can be probed with laser-assisted
      thermal desorption techniques. The UV light enhancement of water desorption is
      strongly light polarization dependent. The electronic structure of the
      ferroelectric copolymer films of vinylidene fluoride with trifluoroethylene films
      is locally altered with incident UV radiation suggesting metastable excited
      states that may involve dipole reorientation.

PMID- 16610894
TI  - Correlation between electronic properties and hydrodesulfurization activity of 4d
      transition-metal sulfides.
AB  - The present study attempts to examine the relationship between electronic
      structure properties exhibited by 4d-transition-metal sulfides (TMSs) in
      connection with the hydrodesulfurization (HDS) catalytic activity. The electronic
      structure is studied by means of a periodic density functional approach using a
      plane-wave basis set and appropriate pseudopotentials. Both bulk and relevant
      surfaces of NbS, NbS(2), MoS(2), TcS(2), RuS(2), Rh(2)S(3), PdS, and PdS(2) have
      been analyzed. High densities of nonbonding states below the Fermi level have
      been found for the TMSs that exhibit good catalytic performance. Therefore, it is
      suggested that the incomplete filling of the band gap at exposed transition metal
      atoms over the catalyst surface plays a determinant role in the HDS reactions. It
      has also been found that the highest HDS activity occurs when the surface-metal
      site density of electronic states has a local minimum at the Fermi level that
      enhances the donation-back-donation mechanism. Additionally, the Sabatier
      principle is qualitatively rationalized in terms of the position of covalent
      bands below the Fermi level.

PMID- 16610895
TI  - Improved hydrogen release from LiB0.33N0.67H2.67 with noble metal additions.
AB  - The hydrogen release behavior of the quaternary hydride LiB(0.33)N(0.67)H(2.67)
      has been successfully improved through the incorporation of small quantities of
      noble metal. Adding 5 wt % Pd either as Pd metal particles or as PdCl(2) reduced
      the temperature T(1/2) corresponding to the midpoint of the hydrogen release
      reaction by DeltaT(1/2) = -43 degrees C and -76 degrees C, respectively. PtCl(2)
      and Pt nanoparticles supported on a Vulcan carbon substrate proved to be even
      more effective, with DeltaT(1/2) = -90 degrees C. The amount of NH(3) released
      during dehydrogenation is reduced compared to that from additive-free material,
      and, more importantly, at temperatures below 210 degrees C hydrogen is released
      with no detectable NH(3). In contrast to additive-free LiB(0.33)N(0.67)H(2.67),
      which melts completely above 190 degrees C and releases hydrogen from the liquid
      state only above approximately 250 degrees C, hydrogen release from
      LiB(0.33)N(0.67)H(2.67) + 5 wt % Pt/Vulcan carbon is accompanied by partial
      melting plus a cascade through a series of solid intermediate phases.
      Calorimetric measurements indicate that both additive-free and Pt-added
      LiB(0.33)N(0.67)H(2.67) release hydrogen exothermically, and hence the reverse
      reaction is thermodynamically unfavorable. By exposing partially dehydrogenated
      samples to high H(2) pressures at modest temperatures, fractional hydrogen uptake
      (roughly 15% of the released hydrogen) has been achieved. The mechanism by which
      noble metals promote hydrogen release is not known, but the behavior is
      consistent with that expected for a catalyst, including a large effect with small
      additions and saturation of the effect at low concentration.

PMID- 16610896
TI  - Unusual infrared spectrum of ethane adsorbed by gallium oxide.
AB  - The present study reports an unusual diffuse reflection Fourier transform (DRIFT)
      spectrum of ethane adsorbed by gallium oxide. One of the stretching C-H bands in
      this spectrum with a maximum at 2753 cm(-1) is more than by 100 cm(-1) shifted
      toward lower frequencies in comparison with gaseous ethane. In addition, the
      relative intensity of this band is unusually high. This indicates a very strong
      polarizability of the corresponding chemical bonds resulting from perturbation of
      ethane by the low coordinated Ga(3+) cations. The assignment of this band to the
      very strongly perturbed initially fully symmetric nu(1) C-H stretching vibration
      is confirmed by a DFT modeling of ethane adsorption by the simplest Ga(2)O(3)
      cluster. The obtained results also indicate heterolytic dissociative adsorption
      and dehydrogenation of ethane by Ga(3+) Lewis sites at elevated temperature. This
      is evidenced by the appearance of new IR bands from zinc alkyl fragments and
      acidic protons followed by decomposition of resulting zinc ethyl species. In
      parallel, the most intense IR band at lower frequency from the most strongly
      polarized C-H chemical bond decreased in intensity. The obtained results indicate
      that these vibrations are involved in subsequent heterolytic dissociative
      adsorption. The obtained results demonstrate that, similar to the shifts of C-H
      stretching vibrations to the low-frequency, intensities of IR C-H stretching
      bands can be also used as an index of chemical activation of adsorbed paraffins
      via their polarization by the low-coordinated cations.

PMID- 16610897
TI  - Size and structure dependence of carbon monoxide chemisorption on cobalt
      clusters.
AB  - We have carried out a series of ab initio calculations to investigate changes in
      the structural and magnetic properties of pristine cobalt clusters upon CO
      chemisorption. Our results show that binding energies of CO to 13-55 atom (0.5
      1.5 nm) cobalt nanoparticles and preferred chemisorption sites depend on the
      cluster structure (whether fcc or icosahedral), size, and surface coverage. In
      addition, we find a strong influence of CO on the magnetism of the cluster,
      leading to magnetic moments smaller than in the bulk, at variance with pristine
      clusters which have magnetic moments larger than the bulk. Our findings suggest
      important changes in catalytic properties of cobalt at the nanoscale. Our theory
      suggests that at the nanoscale cluster size and surface coverage might control
      catalysis.

PMID- 16610898
TI  - Surface structure of (10(-)10) and (11(-)20) surfaces of ZnO with density
      functional theory and atomistic simulation.
AB  - We have calculated the stability of two of the low-index surfaces known to
      dominate the morphology of ZnO as a function of stoichiometry. These two surfaces
      are (10(-)10) and (11(-)20). In each case, two terminations only are stable for a
      significant range of oxygen and hydrogen chemical potential: the pure
      stoichiometric surface and a surface covered in a monolayer of water. The mode by
      which the water adsorbs is however different for the two surfaces considered. On
      the (10(-)10) surface the close proximity of the water molecules means hydrogen
      bonding can occur between adjacent chemiabsorbed water molecules and hence there
      is little difference in the stability of the hydrated and hydroxylated surface,
      and in fact the most stable surface occurs with a combination of dissociated and
      undissociated water adsorption. In the case of the (11(-)20) surface, it is only
      when full dissociation has occurred that a hydrogen-bonding network can form. Our
      results also show good agreement between DFT and atomistic simulations,
      suggesting that potential based methods can usefully be applied to ZnO.

PMID- 16610900
TI  - Controlled amine functionality in self-assembled monolayers via the hidden amine
      route: chemical and electronic tunability.
AB  - A synthetic strategy for fabricating a dense amine functionalized self-assembled
      monolayer (SAM) on hydroxylated surfaces is presented. The assembly steps are
      monitored by X-ray photoelectron spectroscopy, Fourier transform infrared-
      attenuated total reflection, atomic force microscopy, variable angle
      spectroscopic ellipsometry, UV-vis surface spectroscopy, contact angle
      wettability, and contact potential difference measurements. The method applies
      alkylbromide-trichlorosilane for the fabrication of the SAM followed by surface
      transformation of the bromine moiety to amine by a two-step procedure: S(N)2
      reaction that introduces the hidden amine, phthalimide, followed by the removal
      of the protecting group and exposing the free amine. The use of phthalimide
      moiety in the process enabled monitoring the substitution reaction rate on the
      surface (by absorption spectroscopy) and showed first-order kinetics. The
      simplicity of the process, nonharsh reagents, and short reaction time allow the
      use of such SAMs in molecular nanoelectronics applications, where complete
      control of the used SAM is needed. The different molecular dipole of each step of
      the process, which is verified by DFT calculations, supports the use of these
      SAMs as means to tune the electronic properties of semiconductors and for better
      synergism between SAMs and standard microelectronics processes and devices.

PMID- 16610899
TI  - Structures and properties of Newton black films characterized using molecular
      dynamics simulations.
AB  - We used molecular dynamics (MD) simulations to investigate the structures and
      properties of Newton black films (NBF) for several surfactants: sodium dodecyl
      sulfate (SDS), cetyltrimethylammonium bromide (C16TAB), and surfactin using film
      thicknesses up to 10 nm. By calculating the interface formation energy for
      various packing conditions on the surface pressure-area isotherm, we found that
      the most probable surface concentration is approximately 42 A(2)/molecule for SDS
      and C16TAB and approximately 170 A(2)/molecule for surfactin. We then used this
      most probable concentration of each surfactant to simulate NBF with various film
      thicknesses. From analyzing the disjoining pressure-film thickness isotherms with
      the density profiles and the solvation coordination number, we found that the
      increase of the disjoining pressure during the film thinning was coupled with the
      change in inner structure of the NBF (i.e., density profile and the solvation of
      ionic entities). In the range of film thicknesses less than approximately 30 A,
      the disjoining pressures for the SDS and C16TAB were found to be larger than that
      of the surfactin. We predicted the Gibbs elasticity (175 dyn/cm for surfactin;
      109 dyn/cm for C16TAB; 38 dyn/cm for SDS) required to assess the stability of NBF
      against surface concentration fluctuations, and the shear modulus (6.5 GPa for
      the surfactin; 6.1 GPa for the C16TAB; 3.5 GPa for the SDS) and the yield stress
      (approximately 0.8 GPa for surfactin; approximately 0.8 GPa for C16TAB;
      approximately 0.4 GPa for the SDS) to assess the mechanical stability against the
      externally imposed mechanical perturbation.

PMID- 16610901
TI  - STM study of the conformation and reaction of long-chain haloalkanes at Si(111)-7
      x 7.
AB  - Scanning tunneling microscopy (STM) has been used to study the adsorption of 1
      fluoro-, 1-chloro-, and 1-bromo-substituted C(12) alkanes at the Si(111)-7 x 7
      surface, at temperatures from 300 to 500 K. We report self-assembly of these
      physisorbed adsorbates, C(12)H(25)X, to form approximately circular corrals,
      (C(12)H(25)X)(2), with charge transfer to a corralled adatom in each case (cf.
      Dobrin et al. Surf. Sci. 2006, 600, L43). The corrals comprised pairs of
      semicircular horizontal long-chain molecules stable to approximately 100 degrees
      C. At > or =150 degrees C, the corrals desorbed or reacted locally to imprint a
      halogen atom, X-Si, and an adjacent alkane residue, R-Si. The corral height
      profiles, together with the location of the imprinted X-Si resulting from thermal
      or electron-induced surface reaction, led to a picture of the molecular
      configurations in these haloalkane corrals, (C(12)H(25)X)(2), X = F, Cl, Br, and
      the dichloro corrals, 1,12-dichlorododecane, (ClC(12)H(24)Cl)(2).

PMID- 16610902
TI  - Effect of TiO2 crystalline phase composition on the physicochemical and catalytic
      properties of Pd/TiO(2) in selective acetylene hydrogenation.
AB  - Pd/TiO(2) catalysts have been prepared using TiO(2) supports consisting of
      various rutile/anatase crystalline phase compositions. Increasing percentages of
      rutile phase in the TiO(2) resulted in a decrease in Brunauer-Emmett-Teller
      surface areas, fewer Ti(3+) sites, and lower Pd dispersion. While acetylene
      conversions were found to be merely dependent on Pd dispersion, ethylene
      selectivity appeared to be strongly affected by the presence of Ti(3+) in the
      TiO(2) samples. When TiO(2) samples with 0-44% rutile were used, high ethylene
      selectivities (58-93%) were obtained whereas ethylene losses occurred for those
      supported on TiO(2) with 85% or 100% rutile phase. X-ray photoelectron
      spectroscopy and electron spin resonance experiments revealed that a significant
      amount of Ti(3+) existed in the TiO(2) samples composed of 0-44% rutile. The
      presence of Ti(3+) in contact with Pd can probably lower the adsorption strength
      of ethylene resulting in an ethylene gain. Among the five catalysts used in this
      study, the results for Pd/TiO(2)-R44 suggest an optimum anatase/rutile
      composition of the TiO(2) used to obtain high selectivity of ethylene in
      selective acetylene hydrogenation.

PMID- 16610903
TI  - Low temperature H2O and NO2 coadsorption on theta-Al2O3/NiAl(100) ultrathin
      films.
AB  - The coadsorption of H(2)O and NO(2) molecules on a well-ordered, ultrathin theta
      Al(2)O(3)/NiAl(100) film surface was studied using temperature programmed
      desorption (TPD), infrared reflection absorption spectroscopy (IRAS), and X-ray
      photoelectron spectroscopy (XPS). For H(2)O and NO(2) monolayers adsorbed
      separately on the theta-Al(2)O(3)/NiAl(100) surface, adsorption energies were
      estimated to be 44.8 and 36.6 kJ/mol, respectively. Coadsorption systems prepared
      by sequential deposition of NO(2) and H(2)O revealed the existence of coverage
      and temperature-dependent adsorption regimes where H(2)O molecules and the
      surface NO(x) species (NO(2)/N(2)O(4)/NO(2)(-),NO(3)(-)) form segregated and/or
      mixed domains. Influence of the changes in the crystallinity of solid water
      (amorphous vs crystalline) on the coadsorption properties of the
      NO(2)/H(2)O/theta-Al(2)O(3)/NiAl(100) system is also discussed.

PMID- 16610904
TI  - 84% catalyst activity of water-assisted growth of single walled carbon nanotube
      forest characterization by a statistical and macroscopic approach.
AB  - We propose a statistical and macroscopic analysis to estimate the catalyst
      activity of water-assisted growth (super-growth) of single-walled nanotubes
      (SWNT) and to characterize SWNT forests. The catalyst activity was estimated to
      be 84% (+/-6%), the highest ever reported. The SWNT forest was found to be a very
      sparse material where SWNTs represent only 3.6% of the total volume. This
      structural sparseness is believed to play a critical role in achieving highly
      efficient growth.

PMID- 16610905
TI  - Langmuir-Blodgett patterning of phospholipid microstripes: effect of the second
      component.
AB  - We systematically describe the striped pattern formation of the mixed monolayers
      of 1,2-di(2,4-octadecadienoyl)-sn-glycero-3-phosphocholine (DOEPC) and l-alpha
      dipalmitoylphosphatidylcholine (DPPC) from the liquid expanded (LE) phase onto a
      mica surface by Langmuir-Blodgett (LB) transfer. The addition of the second
      component, DOEPC, strongly affects the formation of DPPC stripe patterns. When
      the molar ratio of DPPC and DOEPC is 1:0.1, the horizontal stripes dominate,
      while in the case of pure DPPC monolayer, there are three kinds of patterns:
      horizontal stripes, grids, and vertical stripes. The width and periodicity of
      stripes formed from the mixed monolayers are ca. 4-5 times smaller than those
      formed from pure DPPC patterns at the same transfer conditions, while the widths
      of channels are similar. A phase shift of substrate-mediated microphase
      separation in the two-component system during LB transfer is considered to be the
      mechanism for the influence of the second component on the formation of DPPC
      stripe patterns.

PMID- 16610906
TI  - Physical insights into the photoactivated Ullmann coupling process producing
      highly conjugated oligothiophene films on a copper substrate.
AB  - This paper describes the details of surface reactions producing >100-nm-thick
      conjugated polymer films. When 2,5-diiodothiophene films deposited on copper are
      irradiated with UV at room temperature in Ar environments, oligothiophene films
      are synthesized. The average conjugation length of the produced film varies from
      approximately 7 to 3-4 as the film thickness increases from approximately 100 to
      approximately 500 nm. The X-ray photoelectron spectroscopy analysis of the
      produced films reveals evidence for the formation of organo-copper intermediate
      species at the copper-monomer film interface and their diffusion from the copper
      surface into the monomer film during the photochemical process. A one-dimensional
      diffusion-reaction model is presented to explain the formation, diffusion, and
      reaction of organo-copper intermediates in the multilayer film during the
      photochemical reaction. The model simulation results qualitatively explain the
      decrease of the Ullmann coupling contribution in the photochemical reaction with
      the film thickness.

PMID- 16610907
TI  - Magnetic properties of ferromagnetic quasi-1D copper-peptide compounds: exchange
      interactions and very low temperature phase transitions.
AB  - The magnetic properties of the Cu(II)-peptide compounds (L-tyrosyl-L
      leucinato)Cu(II) and (L-tryptophyl-glycinato)Cu(II), to be identified as
      Cu(II)Tyr-Leu and Cu(II)Trp-Gly, respectively, have been investigated by specific
      heat (0.08 < T < 28 K), dc magnetization (2 < T < 80 K, with B(0) = mu(o)H < or =
      9 T), and ac magnetic susceptibility (with B(0) = 0 for 0.03 < T < 3 K and B(0)
      up to 9 T for 2 < T < 80 K) measurements. Above approximately 1 K, the specific
      heat and magnetization of both compounds display a ferromagnetic (FM) spin chain
      behavior sustained by syn-anti carboxylate bridges connecting equatorially Cu(II)
      ions at about 5 A. To model this behavior, we calculated the eigenvalues of
      Heisenberg chains with up to 20 spins 1/2 and used the method of Bonner and
      Fisher. A global fit of the model to the specific heat and magnetization data
      gives 2J(0)/k(B) = 3.60(5) K and 2.59(5) K for the intrachain exchange
      interactions in Cu(II)Tyr-Leu and Cu(II)Trp-Gly, respectively (H(ex)(i,j) = 
      2J(0) S(i).S(j)). These values of 2J(0) are discussed in terms of structural
      properties of the carboxylate bridges in the two compounds. Using the parameters
      obtained from the global fit, we calculated isothermal susceptibilities in
      agreement with the ac susceptibilities measured with small applied dc magnetic
      fields. However, the ac susceptibility measured with applied dc fields larger
      than 1 T lie between the values calculated for the isothermal and adiabatic
      susceptibilities. At 0.16 K for Cu(II)Tyr-Leu and 0.53 K for Cu(II)Trp-Gly, the
      observed specific heat and magnetic susceptibility display peaks associated to
      three-dimensional magnetic phase transitions. The interchain exchange couplings
      2J(1) producing the 3D magnetic order are ferromagnetic and have magnitudes
      2J(1)/k(B) approximately 0.015 and 0.073 K for Cu(II)Tyr-Leu and Cu(II)Trp-Gly,
      respectively.

PMID- 16610908
TI  - Dynamics in the presence of attractive patchy interactions.
AB  - We report extensive Monte Carlo and event-driven molecular dynamics simulations
      of a liquid composed of particles interacting via hard-sphere interactions
      complemented by four tetrahedrally coordinated short-range attractive ("sticky")
      spots, a model introduced several years ago by Kolafa and Nezbeda (Kolafa, J.;
      Nezbeda, I. Mol. Phys. 1987, 87, 161). To access the dynamic properties of the
      model, we introduce and implement a new event-driven molecular dynamics algorithm
      suited to study the evolution of hard bodies interacting, beside the repulsive
      hard-core, with a short-ranged interpatch square well potential. We evaluate the
      thermodynamic properties of the model in deep supercooled states, where the bond
      network is fully developed, providing evidence of density anomalies. Different
      from models of spherically symmetric interacting particles, the liquid can be
      supercooled without encountering the gas-liquid spinodal in a wide region of
      packing fractions phi. Around an optimal phi, a stable fully connected
      tetrahedral network of bonds develops. By analyzing the dynamics of the model we
      find evidence of anomalous behavior: around the optimal packing, dynamics
      accelerate on both increasing and decreasing phi. We locate the shape of the
      isodiffusivity lines in the (phi - T) plane and establish the shape of the
      dynamic arrest line in the phase diagram of the model. Results are discussed in
      connection with colloidal dispersions of sticky particles and gel-forming
      proteins and their ability to form dynamically arrested states.

PMID- 16610909
TI  - Thermodynamics of hydrogen solution and hydride formation in Pd-Mn alloys. 1.
      Disordered alloys and a correlation effect.
AB  - The thermodynamics of H(2) solution and hydride formation/decomposition have been
      determined by reaction calorimetry (303 K) for disordered face centered cubic
      (fcc) Pd-Mn alloys. This alloy system belongs to the expanded lattice category
      which predicts that and DeltaH(plat) for H(2) absorption should be more
      exothermic than those for Pd; the experimental results are that the former is
      more exothermic, at least at the higher Mn contents, but the latter is not. There
      is a regular decrease in the H capacity (at p(H)2 = 0.2 MPa) with atom fraction
      Mn. A linear dependence of log p(H)2 upon H content is found in the single
      hydride phase for all of these alloys suggesting that DeltaH(H) and DeltaS(H) are
      also linear functions of r in this region. This is confirmed using the
      Pd(0.875)Mn(0.125) alloy which has no two-phase region (303 K). It is shown for
      the Pd(0.875)Mn(0.125) alloy and for Pd that the changes of partial enthalpies
      and entropies with H content are correlated so as to minimize changes of mu(H).

PMID- 16610910
TI  - Thermodynamics of hydrogen solution and hydride formation in Pd-Mn alloys. 2.
      Ordered alloys.
AB  - There are marked differences in H(2) solubilities between ordered and disordered
      Pd-Mn alloys with the largest difference found between the L1(2) and the
      disordered form of the Pd(3)Mn alloy. The thermodynamics of H(2) solution have
      been determined for the L1(2) form, the long-period superstructure (lps), and the
      disordered forms of the Pd(0.80)Mn(0.20) and Pd(0.75)Mn(0.25)(Pd(3)Mn) alloys.
      Relative partial molar enthalpies and entropies were determined mainly by
      reaction calorimetry over the range of H contents accessible from p(H)()2
      approximately 10 Pa to approximately 0.3 MPa (303 K). The enthalpies for
      absorption of H(2) are more exothermic over most of the range of H contents for
      the L1(2) forms of the Pd(3)Mn and Pd(0.80)Mn(0.20) alloys than for their other
      forms. The reaction enthalpies are constant across a relatively wide range of H
      contents for the L1(2) form of the Pd(0.80)Mn(0.20) and Pd(3)Mn alloys indicating
      that there are two-phase coexistence regions (303 K). The H-H attractive
      interaction, which leads to hydride formation, is much greater for the L1(2) than
      for the other forms of the Pd(3)Mn alloy and for Pd itself. It has been found
      that the H-H interaction always decreases in magnitude and, accompanying this,
      the THS (terminal hydrogen solubility) always increases by alloying Pd.(1) The
      L1(2) ordered Pd(3)Mn alloy is an exception to this, and therefore, the
      generalization about THS must be restricted to disordered face centered cubic
      (fcc) Pd alloys.

PMID- 16610911
TI  - Electrical relaxation of bismuth germanate silicate glasses.
AB  - The frequency-dependent electrical data of the bismuth germanate silicate (BGSO)
      glasses have been discussed in the framework of the electric modulus
      representation and the power-law conductivity. The activation energies of the
      mean electric relaxation time and the direct current (dc) conductivity obtained
      by the complex modulus analysis show that the BGSO glasses satisfy the Barton,
      Nakajima, and Namikawa (BNN) relation. The proper relation between the exponent
      of the power-law conductivity and the stretched exponential of the modulus
      representation is shown. The temperature- and frequency-dependent characteristics
      of non-Debye behavior are discussed. The scaling properties of both the modulus
      M*(omega) and the alternating current (ac) conductivity sigma(omega) are
      examined.

PMID- 16610912
TI  - Biofilm effects on the peroxidase-oxidase reaction.
AB  - In experiments on the kinetics of the peroxidase-oxidase oscillatory reaction in
      pH 5.l acetate buffer, biofilms form in less than 48 h on the quartz reactor
      surface. The nominally homogeneous peroxidase system shows dynamical changes in
      response to this biofilm growth, partially explaining subtle differences among
      dynamics observed over time and between laboratories. Kinetics data and model
      computations are correlated with micrographs of biofilm formation. It is evident
      that bare quartz also interacts with reaction species, so that the surface area
      to-volume ratio is an important parameter on which observed dynamics depend.

PMID- 16610913
TI  - Probing the kinetics of membrane-mediated helix folding.
AB  - The kinetics of peptide-membrane association have been studied previously using
      stopped-flow tryptophan fluorescence; however, such experiments do not directly
      report the coil-to-helix transition process, which is a hallmark of peptide
      membrane interaction. Herein, we report a new method for directly assessing the
      kinetics of the helix formation accompanied by the peptide-membrane association.
      This method is based on the technique of fluorescence resonance energy transfer
      (FRET) and an amino acid FRET pair, p-cyano-L-phenylalanine and tryptophan. To
      demonstrate the utility of this method, we have studied the membrane-mediated
      helix folding dynamics of a mutant of magainin 2, an antibiotic peptide found in
      the skin of the African clawed frog, Xenopus laevis. Our results indicate that
      the coil-to-helix transition occurs during the binding of the peptide to the
      lipid vesicle (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1-palmitoyl-2
      oleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)], 3:1, wt/wt) but prior to the full
      insertion of the peptide into the hydrophobic region of the lipid bilayers.

PMID- 16610914
TI  - Density functional calculations of ATP systems. 1. Crystalline ATP hydrates and
      related molecules.
AB  - Adenosine 5'-triphosphate (ATP) is an essential energy carrier in mammalian and
      other cells, and its hydrolysis to the diphosphate (ADP) in the presence of metal
      cations (e.g., Mg(2+) or Ca(2+)) is one of the most prevalent biochemical
      reactions. We describe here density functional (DF) calculations on closely
      related systems and compare the results with other calculations and available
      experimental data: Na(H2O)n +, Mg(H2O)n 2+, and Ca(H2O)n 2+ clusters (n = 1, 4
      7), the crystalline pyrophosphates Mg(2)P(2)O(7).6H2O and alpha
      CaNa(2)P(2)O(7).4H2O, and crystalline Na(2)ATP.3H2O. The last of these comprises
      asymmetric units of ATP dimers (monomers A and B) in a double-protonated state
      H(2)(ATP)(2-). The calculated structures agree well with available measurements
      and provide additional information, including the location of the H atoms.
      Analysis of the dipole moments of individual ATP monomers and their dimers shows
      that the crystal comprises blocks of opposing dipoles. Replacing one Na+ ion with
      Mg2+ or Ca2+ results in a significant elongation of the terminal bridging P-O
      bond. The calculations provide benchmarks for the use of DF methods in ATP
      systems and are used in the companion paper to study the hydrolysis of ATP at the
      active site of the protein actin.

PMID- 16610915
TI  - Density functional calculations of ATP systems. 2. ATP hydrolysis at the active
      site of actin.
AB  - The hydrolysis of adenosine 5'-triphosphate (ATP) at the active site of actin has
      been studied using density functional calculations. The active site is modeled by
      the triphosphate tail of ATP, an Mg cation, surrounding water molecules, and the
      nearby protein residues. Four reaction paths have been followed by constraining
      coordinates that allow phosphate stretching, nucleophilic attack of the catalytic
      water, and OH(-) formation via water deprotonation. The lowest-energy barrier
      (21.0 kcal/mol) is obtained for a dissociative reaction where the terminal
      phosphate breaks on approaching the catalytic water, followed by proton release
      via a proton wire mechanism. A higher barrier (39.6 kcal/mol) results for an
      associative reaction path where OH(-) is formed first, with a pentacoordinated
      phosphorus atom (P-O distances 2.1 A). Stretching the terminal bridging P-O bond
      results in bond rupture at 2.8 A with an energy barrier of 28.8 kcal/mol. The
      residues Gln137 and His161 are not important in the reactions, but insight into
      their roles in vivo has been obtained. The favored coordination of the end
      products H(2)PO(4)(-) and ADP(3-) includes a hydrogen bond and an O-Mg-O bridge
      between the phosphates as well as a hydrogen bond between H(2)PO(4)(-) and the
      Ser14 side chain. The total energy is 2.1 kcal/mol lower than in the initial
      reactants. Classical simulations of ATP- and ADP.P(i)-actin show few hydrolysis
      induced differences in the protein structure, indicating that phosphate migration
      is necessary for a change in conformation.

PMID- 16610916
TI  - Structural effects of a basic peptide on the organization of
      dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylserine membranes: a
      fluorescent resonance energy transfer study.
AB  - We studied the effect of a model basic peptide, hexalysiltryptophan, on the
      organization of dipalmitoylphosphatidylcholine/dipalmitoylphosphatidylserine
      unilamellar vesicles by means of fluorescent resonance energy transfer (FRET)
      between fluorescently labeled phospholipids. Several FRET theoretical models
      assuming different bilayer geometries and probe distributions were fitted to the
      time-resolved data. The experiments were carried out at two temperatures in
      different regions of the lipid mixture phase diagram. At 45 degrees C, the
      expected gel/fluid phase separation was verified by model fitting in peptide-free
      vesicles, which from the FRET approach means that domains are larger than
      approximately 200 A. No noticeable alteration of membrane organization was
      detected upon increasing the peptide concentration. At variance, for the single
      fluid phase at 60 degrees C, there was a large increase in FRET efficiency upon
      peptide addition to the lipid vesicles, mainly caused by peptide-induced vesicle
      aggregation. The system gradually changed from unilamellar lipid vesicles to a
      multibilayer geometry, and a limit lamellar repeat distance of approximately 57 A
      was recovered. Furthermore, no evidence for lateral domain formation on the FRET
      length scale was found at this temperature, the cationic peptide being only able
      to induce local lipid demixing, causing a short-range sequestration of 2-3 acidic
      lipids around each surface-adsorbed peptide.

PMID- 16610917
TI  - Hydrogen bonding affects the [NiFe] active site of Desulfovibrio vulgaris
      Miyazaki F hydrogenase: a hyperfine sublevel correlation spectroscopy and density
      functional theory study.
AB  - Pulse electron paramagnetic resonance and hyperfine sublevel correlation
      spectroscopy have been used to investigate nitrogen coordination of the active
      site of [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki F in its oxidized
      "ready" state. The obtained (14)N hyperfine (A = [+1.32, +1.32, +2.07] MHz) and
      nuclear quadrupole (e(2)qQ/h = -1.9 MHz, eta = 0.37) coupling constants were
      assigned to the N(epsilon) of a highly conserved histidine (His88) by studying a
      hydrogenase preparation in which the histidines were (15)N labeled. The histidine
      is hydrogen-bonded via its N(epsilon)-H to the nickel-coordinating sulfur of a
      cysteine (Cys549) that carries an appreciable amount of spin density. Through the
      hydrogen bond a small fraction of the spin density ( approximately 1%) is
      delocalized onto the histidine ring giving rise to an isotropic (14)N hyperfine
      coupling constant of about 1.6 MHz. These conclusions are supported by density
      functional calculations. The measured (14)N quadrupole coupling constants are
      related to the polarization of the N(epsilon)-H bond, and the respective hydrogen
      bond can be classified as being weak.

PMID- 16610919
TI  - Molecular mechanical devices based on quinone-pyrrole and quinone-indole dyads: a
      computational study.
AB  - A set of intramolecularly connected dyads consisting of a quinone unit and a
      pyrrole or indole moiety have been designed and evaluated in quantum-chemical
      calculations. It is shown computationally for several systems, depending on the
      length and attachment points of the interconnecting chains, that a reduction of
      the quinone to the semiquinone radical anion or quinolate dianion state leads to
      a reversible intramolecular reorientation from a pi-stacked to a T-stacked
      arrangement. In the rearranged structures, a hydrogen bond from the pyrrole or
      indole N-H function to the semiquinone or quinolate pi-system is created upon
      reduction. In some systems, hydrogen bonds to the semiquinone or quinolate oxygen
      atoms are partly feasible and will be preferred over T-stacking. The choice of
      systems has been based on recent computational observations related to
      photosystem I. Systems with pyrrole or indole units should provide a better basis
      for the envisioned molecular motor than recently proposed quinone-benzene dyads.
      The intramolecular interactions modify the quinone redox potentials. Electronic g
      tensors have been computed for the semiquinone states. These reflect
      characteristically the presence and nature of hydrogen bonds to the semiquinone
      and represent suitable electron paramagnetic resonance spectroscopic probes for
      the preferred structures. Intramolecular proton transfer is possible in the
      dianionic state.

PMID- 16610918
TI  - Diffusion of lipid-like single-molecule fluorophores in the cell membrane.
AB  - The dicyanomethylenedihydrofuran (DCDHF) class of single-molecule fluorophores
      contains an amine donor and a dicyanomethylenedihydrofuran acceptor linked by a
      conjugated unit (benzene, naphthalene, or styrene). Molecules in this class have
      a number of useful properties in addition to those usually required for single
      molecule studies (such as high fluorescence quantum yield and photostability),
      including second-order optical nonlinearity, large ground-state dipole moment,
      and sensitivity to local environment. Moreover, most DCDHF molecules have
      amphiphilic structures, with a polar dicyanomethylenedihydrofuran headgroup and
      nonpolar hydrocarbon tails on the amine or furan ring, and can be used as
      fluorescent lipid analogues for live cell imaging. Here we demonstrate that
      individual molecules of several different DCDHF lipid analogues can be observed
      diffusing in the plasma membrane of Chinese hamster ovary cells. The
      photophysical and diffusive behaviors of the DCDHF lipid analogues in membranes
      are described and are found to be competitive with the well-known lipid probe N
      (6-tetramethylrhodaminethiocarbamoyl)-1,2-dihexadecanoyl-sn-glycero-3
      phosphoethanolamine.

PMID- 16610920
TI  - Curing processes in solvent-borne alkyd coatings with different drier
      combinations.
AB  - The concern regarding the effect of chemicals on the environment has increased
      considerably in recent years. Nowadays, technological developments in the coating
      industry are largely influenced by environmental issues and subsequent
      legislation. One of these issues is the tendency to replace cobalt as a catalyst
      with more environmentally friendly alternatives, because studies have indicated
      possible carcinogenicity. Not much knowledge is available on the effects of
      catalysts (driers) on the in-depth drying of alkyd coatings. Therefore we have
      studied the effect of cobalt as a primary drier combined with Ca and Zr as
      secondary driers on the in-depth curing of high solid solvent-borne alkyds. The
      profiling of the curing of alkyd coatings is performed with a new high-spatial
      resolution NMR setup. In this study, two effects observed in the solvent-borne
      alkyd coatings are investigated. One is that when Ca and Zr are added as
      secondary driers the speed of the observed cross-linking front increases. Second,
      in the deeper un-cross-linked region below the front, the signal of the NMR
      profiles was found to decrease proportional to . This could be explained by the
      presence of slowly reacting species that diffuse into the deeper uncured region
      of the coating, after which they cross-link. The model describing the effect of
      these reactive species also indicates that the signal decrease is inversely
      proportional to coating thickness L, which was confirmed by additional
      measurements.

PMID- 16610921
TI  - Toward evidence-based assessment for coverage and reimbursement of laboratory
      based diagnostic and genetic tests.
AB  - Despite the pervasiveness of laboratory tests and their importance to medicine,
      evidence for their appropriate use often is very limited. In this article, we
      argue for a fundamental restructuring of the process by which laboratory tests
      are evaluated and reimbursed. We present an approach that would promote more
      evidence- based appraisals for laboratory tests. In addition, we urge that
      coverage and reimbursement for laboratory tests move toward an evidence- and
      value-based approach, using the tools that largely have been adopted for
      pharmaceuticals by many US healthcare payers. To address this information gap for
      laboratory tests, we note several potential strategies to encourage
      manufacturers, laboratory service providers, and payers to collect outcome and
      cost data that will better support effective use of new laboratory tests.
      Integral to increasing appropriate use and reimbursement will be the development
      of a common language and format for dialogue--facilitating the development,
      review, and delivery of evidence-based tests by manufacturers, clinical
      laboratories, and healthcare payers.

PMID- 16610922
TI  - Economic evaluation of controlled-release oxycodone vs oxycodone-acetaminophen
      for osteoarthritis pain of the hip or knee.
AB  - OBJECTIVE: To examine, in routine practice, the effectiveness and cost
      effectiveness of oxycodone (OxyContin) compared with standard therapy for
      osteoarthritis pain. STUDY DESIGN: Open-label active-controlled randomized
      naturalistic 4-month study of oxycodone vs a combination of oxycodone
      acetaminophen (Percocet). METHODS: Outcomes and health resource utilization data
      were collected by telephone interview. Effectiveness was measured among 485
      patients as the proportion having at least 20% improvement from baseline in the
      Western Ontario and McMaster Universities Osteoarthritis Index pain score.
      Quality-adjusted life-years (QALYs) were calculated from the Health Utilities
      Index 3 score. Cost-effectiveness was measured as cost per patient improved and
      the QALYs gained, using generic oxycodone-acetaminophen in the base case for the
      healthcare and societal perspectives. Uncertainty was evaluated using multiple 1
      way sensitivity analyses and cost-effectiveness acceptability curves. RESULTS:
      Improvement occurred in 62.2% of patients with oxycodone and in 45.9% of patients
      with oxycodone-acetaminophen (P < .001). After adjustment for baseline
      differences, 0.0105 QALYs were gained with oxycodone compared with oxycodone
      acetaminophen (P = .17). The mean societal costs per patient during 4 months were
      7379 US dollars and 7528 US dollars for oxycodone and oxycodone-acetaminophen,
      respectively (P = .33). Oxycodone was more effective and less costly than
      oxycodone-acetaminophen based on the societal perspective (including costs
      associated with time lost). Based on the healthcare perspective (excluding costs
      associated with time lost), the cost-effectiveness of oxycodone was 4883 US
      dollars per patient improved and 75,810 US dollars per QALY gained. The base-case
      results were robust. CONCLUSIONS: From the societal perspective, oxycodone was
      more effective and less costly than oxycodone-acetaminophen. From the healthcare
      perspective, oxycodone (compared with generic oxycodone-acetaminophen) fell
      within the acceptable range of cost-effectiveness between 50,000 US dollars and
      100,000 US dollars per QALY gained.

PMID- 16610923
TI  - What will it take for disease management to demonstrate a return on investment?
      New perspectives on an old theme.
AB  - BACKGROUND: Disease management programs are expected (and usually contractually
      required) to reduce total costs in the diseases they manage. OBJECTIVES: To
      discuss the appropriateness of using utilization indexes in lieu of cost and the
      importance of reviewing utilization trends to determine whether sufficient
      opportunity exists for a program to be financially effective; and to conduct an
      analysis to determine the number of admissions that must be reduced for a program
      to achieve various levels of return on investment. STUDY DESIGN: Descriptive.
      METHODS: Historical inpatient cost trends, discharges per 10,000 population, the
      mean length of stay, and emergency department visits per 10,000 population for
      acute myocardial infarction, congestive heart failure, asthma, and diabetes
      mellitus are presented. A "number-needed-to-decrease" analysis is performed to
      determine the number of admissions or emergency department visits that must be
      reduced to meet varying levels of return on investment. RESULTS: (1) Hospital
      days per 10,000 population for these conditions trended downward, while costs
      during the same period escalated. (2) Discharge and emergency department visit
      rates per 10,000 population were flat and low during the observation period,
      while the mean length of stay declined. Results of the number-needed-to-decrease
      analysis suggest that disease management programs will have to decrease
      admissions 10% to 30% to cover program fees alone. CONCLUSION: A review of
      historical utilization trends and a number-needed-to-decrease analysis should be
      conducted before disease management program implementation to determine whether
      sufficient opportunity exists to reduce utilization to levels that will ensure a
      positive return on investment.

PMID- 16610924
TI  - Effective diabetes care by a registered nurse following treatment algorithms in a
      minority population.
AB  - OBJECTIVE: To compare usual care with nurse-directed care for patients with
      diabetes. STUDY DESIGN: Randomized before-after trial. METHODS: Diabetic patients
      were randomly selected for a diabetes managed care program (DMCP), in which a
      specially trained registered nurse, supervised by an endocrinologist, followed
      detailed treatment algorithms. Process and outcome measures during the year
      before DMCP entry were compared with those during the first year of DMCP
      enrollment. RESULTS: A total of 367 patients completed a full year in the DMCP.
      Data from the prior year were available for 331 patients. Among a subset of
      Latino patients, 95% earned less than 25,000 US dollars and 73% had an education
      of 6th grade or less. Process measures recommended by the American Diabetes
      Association (ADA) were met 98% of the time during the DMCP year compared with 54%
      of the time during the prior year (P <.001). Mean glycosylated hemoglobin (A1C)
      levels fell from 9.3% to 8.7% in the year before entry into the DMCP and to 7.0%
      by the end of the first DMCP year (P < .001). At DMCP entry, 28% met the ADA A1C
      goal of <7%; 60% did so at the end of the year. Fifty-one percent met the ADA low
      density lipoprotein cholesterol goal at entry into the DMCP compared with 82% at
      the end of the year. CONCLUSION: A nurse making clinical decisions based on
      detailed treatment algorithms did a better job of achieving ADA-recommended
      process and outcome measures than physicians providing usual care.

PMID- 16610925
TI  - Promoting repeat tobacco dependence treatment: are relapsed smokers interested?
AB  - BACKGROUND: Promotion of repeat tobacco dependence treatment among relapsed
      smokers interested in "recycling" (repeat quit attempt) may be a promising
      approach to increase quit rates. OBJECTIVE: To report relapsed smokers' interest
      in recycling and their treatment preferences. STUDY DESIGN: Descriptive analysis
      of a population of relapsed smokers who were randomized to receive a recycling
      intervention strategy to increase tobacco dependence treatment rates, as part of
      a randomized controlled trial at 5 Veterans Affairs medical centers. METHODS:
      Individuals prescribed a tobacco dependence medication in 2002 were eligible and
      were identified from the Department of Veterans Affairs Pharmacy Benefits
      Management database. Intervention group participants (n = 951) were contacted for
      a standardized telephone interview approximately 6 months after the prescription
      fill date to assess smoking status, interest in recycling, and treatment
      preferences. Bivariate analyses and generalized linear mixed-model regressions
      were used to describe outcomes. RESULTS: The response rate to the intervention
      telephone call was 62% (586/951), at which 61% (357/586) of respondents had
      relapsed. Almost two thirds of relapsed smokers were interested in recycling
      within 30 days. Of these, 91% wanted behavioral or pharmacologic smoking
      cessation treatment, and 64% wanted behavioral and pharmacologic treatment. In
      multivariate analyses, independent predictors of interest in recycling within 30
      days included black race, lower smoking level, and greater number of smoking
      related medical conditions. CONCLUSION: Most smokers who attempt to quit but
      relapse want to quit again right away, and most are interested in receiving
      behavioral and pharmacologic treatment.

PMID- 16610926
TI  - Markedly enhanced cytolysis by E1B-19kD-deleted oncolytic adenovirus in
      combination with cisplatin.
AB  - Oncolytic adenoviruses are currently being developed as novel antitumor
      therapeutics. To enhance their therapeutic potential, adenoviruses are being
      administered in combination with standard chemotherapy. Adenoviral vectors used
      in these clinical trials, however, can be destructive as they encode intact E1B
      19-kDa protein, which can block the apoptotic pathway induced by a variety of
      chemotherapeutic agents. Previously, we have shown that oncolytic adenovirus Ad
      DeltaE1B19/55, deleted for sequence encoding E1B 19-kDa and E1B 55-kDa proteins,
      exhibits marked enhancement in cytolytic and apoptotic activity [Kim, J., Cho,
      J.Y., Kim, J.H., Jung, K.C., and Yun, C.O. (2002). Cancer Gene Ther. 9, 725-736].
      In the current study, we assess the therapeutic value of Ad- DeltaE1B55 and Ad
      DeltaE1B19/55 in combination with cisplatin. A marked increase in cytotoxicity
      was observed for both Ad-DeltaE1B55 and Ad-DeltaE1B19/55 when combined with
      cisplatin. Relative to each other in all cell lines examined, the combination of
      the double-deleted adenovirus, Ad-DeltaE1B19/55, plus cisplatin exhibited a
      greater cell-killing effect than did the single-deleted adenovirus, Ad
      DeltaE1B55, plus cisplatin. Propidium iodide staining and TUNEL analysis also
      revealed that the combination of cisplatin with Ad-DeltaE1B19/55 caused greater
      induction of apoptosis than that with Ad-DeltaE1B55. Similarly, in vivo, the
      combination of Ad-DeltaE1B55 or Ad-DeltaE1B19/55 with cisplatin also induced
      greater antitumor effect in a human cervical xenograft model. TUNEL staining
      showed that the apoptotic level was significantly higher in tumor tissue treated
      with Ad-DeltaE1B19/55 plus cisplatin than with any other treatment. In addition,
      viral presence was confirmed by immunohistological staining, with increased
      numbers of adenoviral particles detected in wider areas of tumors treated with Ad
      DeltaE1B19/55 oncolytic adenovirus plus cisplatin. Taken together, these findings
      demonstrate that cisplatin in combination with E1B- 19kD-deleted oncolytic
      adenovirus may enhance therapeutic efficacy (via active induction of apoptosis),
      eliciting a greater efficacy profile than that with E1B-19kD-expressing oncolytic
      adenovirus.

PMID- 16610927
TI  - Improved hepatic transduction, reduced systemic vector dissemination, and long
      term transgene expression by delivering helper-dependent adenoviral vectors into
      the surgically isolated liver of nonhuman primates.
AB  - Helper-dependent adenoviral vectors (HDAds) are attractive vectors for liver
      directed gene therapy because they can mediate sustained, high-level transgene
      expression without chronic toxicity. However, high vector doses are required to
      achieve efficient hepatic transduction by systemic delivery because of a
      nonlinear dose response. Unfortunately, such high doses result in systemic vector
      dissemination and dose-dependent acute toxicity with potentially severe and
      lethal consequences. We hypothesize that the threshold to efficient hepatic
      transduction may be circumvented by delivering the vector into the surgically
      isolated liver via the portal vein. Total hepatic isolation was achieved by
      occluding hepatic inflow from the portal vein and hepatic artery and by occluding
      hepatic venous outflow at the inferior vena cava. We demonstrate in nonhuman
      primates that this approach resulted in significantly higher efficiency hepatic
      transduction with reduced systemic vector dissemination compared with systemic
      intravascular delivery. This method of delivery was associated with transient
      acute toxicity, the severity of which was variable. Importantly, stable, high
      levels of transgene expression were obtained for at least 665 days for one baboon
      and for at least 560 days for two baboons with no evidence of long-term toxicity.

PMID- 16610928
TI  - Extracellular superoxide dismutase with vaccinia virus anti-inflammatory protein
      35K or tissue inhibitor of metalloproteinase-1: Combination gene therapy in the
      treatment of vein graft stenosis in rabbits.
AB  - Bypass graft surgery is limited by stenosis of vein grafts. Neointimal formation
      in vein graft stenosis is affected by oxidative stress, acute inflammatory
      response, and proliferation. Gene therapy offers a novel treatment strategy for
      vein graft stenosis because gene transfer can be done ex vivo during the graft
      operation. In this study we used adenovirus-mediated ex vivo gene transfer of
      extracellular superoxide dismutase (EC-SOD) alone or in combination with tissue
      inhibitor of metalloproteinase-1 (TIMP-1) or vaccinia virus antiinflammatory
      protein 35K to prevent vein graft stenosis in a jugular vein graft model in
      normocholesterolemic New Zealand White rabbits. Vein grafts were analyzed 14 and
      28 days after the gene transfer, using histological methods. It was found that at
      the 2-week time point EC-SOD + 35K and EC-SOD + TIMP-1 combinations delivered by
      gene transfer were the most efficient treatments in decreasing neointimal
      formation. At the 4-week time point the effect was seen only in the EC-SOD + TIMP
      1 combination group. The combination of antiinflammatory proteins (EC-SOD + 35K)
      was the most effective in reducing macrophage accumulation, which was still
      significant at the 4-week time point, but this did not prevent vein graft
      thickening. In conclusion, oxidative, inflammatory, and proliferative processes
      are important for neointimal formation in vein graft stenosis. In the rabbit
      model of vein graft disease, combination gene therapy with antioxidative,
      antiinflammatory, and antiproliferative genes was effective in decreasing
      neointimal formation. This may be because two different genes may more
      efficiently affect different pathogenetic pathways at the early stage of the
      disease process than gene transfer approaches based on single genes.

PMID- 16610929
TI  - Vaccination with replication-deficient recombinant adenoviruses encoding the main
      surface antigens of toxoplasma gondii induces immune response and protection
      against infection in mice.
AB  - We have generated recombinant adenoviruses encoding three genetically modified
      surface antigens (SAGs) of the parasite Toxoplasma gondii, that is, AdSAG1,
      AdSAG2, and AdSAG3. Modifications included the removal of their
      glycosylphosphatidylinositol (GPI) anchoring motifs and, in some cases, the
      exchange of the native signal peptide for influenza virus hemagglutinin signal
      sequence. Adenovirus immunization of BALB/c mice elicited potent antibody
      responses against each protein, displaying a significant bias toward a helper T
      cell type 1 (Th1) profile in animals vaccinated with AdSAG1. Furthermore, the
      presence of parasite-specific IFN-gamma-producing T cells was analyzed by
      proliferation assays and enzyme-linked immunospot assays in the same animals.
      Splenocytes from immunized mice secreted IFN-gamma after in vitro stimulation
      with tachyzoite lysate antigen or with a fraction enriched for membrane-purified
      GPI-anchored proteins (F3) from the T. gondii tachyzoite surface. Epitopes
      recognized by CD8+ T cells were identified in SAG1 and SAG3, but not SAG2,
      sequences, although this protein also induced a specific response. We also tested
      the capacity of the immune responses detected to protect mice against a challenge
      with live T. gondii parasites. Although no protection was observed against
      tachyzoites of the highly virulent RH strain, a significant reduction in cyst
      loads in the brain was observed in animals challenged with the P-Br strain. Thus,
      up to 80% of the cysts were eliminated from animals vaccinated with a mixture of
      the three recombinant viruses. Because adenoviruses seemed capable of inducing
      Th1-biased protective immune responses against T. gondii antigens, other parasite
      antigens should be tested alone or in combination with those described here to
      further develop a protective vaccine against toxoplasmosis.

PMID- 16610930
TI  - Long-term efficacy of adeno-associated virus serotypes 8 and 9 in hemophilia a
      dogs and mice.
AB  - We reported total correction of blood coagulation plasma factor VIII (FVIII)
      activity, using adeno-associated virus serotype 8 (AAV8) vectors for liver
      specific gene transfer in hemophilia A mice. We now show, irrespective of
      immunosuppression or route of administration, total long-term correction of
      hemophilia A mice with pseudotyped AAV8 and AAV9 vectors. We delivered two FVIII
      vectors, one expressing canine heavy chain and the other expressing canine light
      chain. Interestingly, when these vectors were given by hepatic portal vein to
      hemophilia A dogs, only modest FVIII levels were seen despite the species
      specific transgene. No dogs treated developed FVIII inhibitors. However, of three
      dogs treated with AAV8 vector, the single male, given 1.25 x 10(13) genome copies
      per vector per kilogram (GC/vector/kg), maintained a level of >4.5% for more than
      2 years. In contrast, the two female dogs expressed only 2% FVIII activity
      despite receiving higher doses of 1.52 x 10(13) and 3 x 10(13) GC/vector/kg,
      respectively. On the other hand, a male dog treated with AAV9 vector at a low
      dose (6 x 10(12) GC/vector/kg) maintained FVIII levels of 2-2.5% of normal
      without bleeding for 200 days (observation ongoing). Although hemophilia A mice
      were not predictive of vector efficacy in dogs, the two treated male dogs became
      symptom-free for long periods. Even so, translation of these robust vectors
      either in appropriate large animals or human beings remains challenging.

PMID- 16610932
TI  - Clinical trial design issues raised during recombinant DNA advisory committee
      review of gene transfer protocols.
AB  - Gene transfer clinical trial protocols are reviewed by the Recombinant DNA
      Advisory Committee (RAC). Identifying the design concerns and suggestions
      commonly raised during RAC review may help investigators and sponsors shorten the
      process of protocol development and improve the quality of gene transfer trials.
      We therefore examined 53 full public reviews of gene transfer clinical trial
      protocols performed by the RAC between December 2000 and June 2004 to determine
      what trial design concerns or suggestions RAC members raised during written
      review or public discussion or in the formal letter to investigators after the
      review was completed. We also determined how frequently these concerns were
      raised. We found that RAC members raised issues regarding selection of subjects
      in 89% of reviews, dose escalation in 77%, selection of safety end points in 76%,
      biological activity measures in 66%, and overall design in 60% of reviews. The
      most common issue raised by RAC reviewers was the need to exclude subjects at
      increased risk for adverse events. Furthermore, in 89% of reviews, at least one
      design issue pertaining to safety of participants was raised. In 91% of reviews,
      at least one design concern was presented as a written RAC recommendation or
      concern to the investigator after the public review. When submitting protocols
      for RAC review, investigators and sponsors might devote more attention to issues
      that RAC reviewers commonly raise. Such attention might help strengthen clinical
      trial protocols, shorten the protocol development process, and enhance the
      protection of research participants.

PMID- 16610931
TI  - Prevalence of neutralizing antibodies against adeno-associated virus (AAV) types
      2, 5, and 6 in cystic fibrosis and normal populations: Implications for gene
      therapy using AAV vectors.
AB  - Adeno-associated virus (AAV) vectors are promising candidates for gene therapy
      directed to the lungs, in particular for treatment of cystic fibrosis (CF). In
      animal models of lung gene transfer, neutralizing antibodies in serum made in
      response to vector exposure have been associated with a partial to complete block
      to repeat transduction by vectors with the same capsid type, thus transduction by
      AAV vectors might be inefficient in humans previously exposed to the same AAV
      type. AAV type 2 (AAV2) has been used in clinical trials of lung gene transfer,
      but AAV5 and AAV6 have been shown to mediate more efficient transduction in
      rodent lungs and in cultured human airway epithelia compared with that of AAV2.
      Here we have measured neutralizing antibodies against AAV type 2, 5, and 6
      vectors in serum from children and adults with CF, and from normal adults. About
      30% of adults were seropositive for AAV2, 20-30% were seropositive for AAV6, and
      10-20% were seropositive for AAV5. CF children were seropositive for AAV type 2,
      5, or 6 at rates of 4-15%. All individuals seropositive for AAV6 were also
      seropositive for AAV2, and the AAV6 titer was low compared with the AAV2 titer.
      AAV5-positive sera were lower both in titers and rates than those seen for AAV6.
      The results indicate that AAV type 2, 5 or 6 exposure is low in CF and control
      populations and even lower in CF children.

PMID- 16610933
TI  - Effect of serotype 5 adenoviral and serotype 2 adeno- associated viral vector
      mediated gene transfer to salivary glands on the composition of saliva.
AB  - Key to the development of a useful clinical therapy is the minimization of side
      effects. Routine safety testing, however, does not provide information about the
      physiological status of many potentially useful gene transfer target sites. In
      this study, we evaluated the longitudinal effects of intrasalivary duct delivery
      of recombinant serotype 5 adenoviral (rAd5; 10(9)-10(10) particles/gland in rats)
      and recombinant serotype 2 adeno-associated viral (rAAV2; 10(8)-10(9)
      particles/gland in mice) vectors on salivary composition. Both vectors led to
      modest, transient alterations in several salivary components that thereafter
      returned to normal. The changes suggested two initial specific consequences of
      rAd5 and rAAV2 vector administration: (1) a modest breach of the mucosal barrier
      in the targeted glands, indicated by elevations in salivary albumin, total
      protein, and Na+ levels, and (2) an innate host response, indicated by transient
      elevations in either salivary lactoferrin and IgA levels (rAd5) or mucin (rAAV2).
      These studies are consistent with the notion that administration of modest doses
      of rAd5 and rAAV2 vectors to salivary glands for a therapeutic purpose can be
      accomplished without severe or permanent injury to the target tissue, or
      compromise to its essential exocrine physiological function.

PMID- 16610934
TI  - An adult dog with cyclic neutropenia treated by lentivirus- mediated delivery of
      granulocyte colony-stimulating factor.
AB  - Cyclic neutropenia occurs in humans and gray collie dogs, is characterized by
      recurrent neutropenia, and is treated by daily injections of recombinant
      granulocyte colony-stimulating factor (G-CSF). After showing that canine
      recombinant G-CSF increased neutrophil counts in an affected dog, we administered
      intramuscularly 2 x 10(9) infectious units (IU) of a lentiviral vector encoding
      canine G-CSF cDNA. Elevated, therapeutic neutrophil production was obtained for
      nearly 18 months. Lentiviral vector treatment provided a mean neutrophil count of
      29,230 +/- 12,930 cells/microl, which was significantly increased over both the
      pretreatment value (5,240 +/- 4,800 cells/microl; p < 0.0001) and the neutrophil
      count during G-CSF administration (17,820 +/- 11,100 cells/microl; p < 0.0001).
      By systemic infusion of recombinant G-CSF to normal dogs we estimated that 2 x
      10(9) IU of lentivirus delivered 3.5 microg of G-CSF per kilogram per day. After
      lentiviral vector treatment the gray collie gained weight, showed no clinical
      signs of infection and fever, and no longer needed housing in a pathogen-free
      environment. Genomic DNA harvested from muscle at the injection sites was
      positive for provirus, whereas gonad, lung, spleen, heart, liver, kidney, and
      noninjected muscle samples were negative. These studies show that an adult animal
      is responsive long-term to lentivirus-mediated G-CSF delivery, suggesting this
      approach may be applied for treatment of adult patients with cyclic and other
      neutropenias.

PMID- 16610935
TI  - Development of high-throughput functional screening of therapeutic genes, using a
      hemagglutinating virus of Japan envelope vector.
AB  - Isolation of effective therapeutic genes is critical for the advancement of gene
      therapy for various diseases, including vascular diseases and cancers. The goal
      of the present study was to screen a human cDNA library, using a hemagglutinating
      virus of Japan envelope (HVJ-E) vector, to isolate candidate genes with potent
      therapeutic potential. The advantages of a high-throughput functional screening
      system based on the HVJ-E vector include (1) rapid preparation of the vector
      containing the DNA library, (2) effective fusion-mediated transfer of the
      plasmids to various cells with minimal toxicity, and (3) easy cloning of
      candidate genes by transformation of Escherichia coli. These advantages resulted
      in a lower probability of damage to isolated clones and in minimization of the
      time needed to screen for candidate genes. Screening of a human heart library for
      candidate genes to regulate endothelial cell growth identified three growth
      stimulating genes, as evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and c-fos
      promoter activity, the products of which were more potent than vascular
      endothelial growth factor. Similarly, two growth-inhibiting genes were
      identified, the effects of which were similar to angiostatin. Overall, this novel
      system will help advance our understanding of cell biology and promote the
      utility of human gene therapy.

PMID- 16610938
TI  - Genzyme launches diagnostic to monitor Gleevec resistance.

PMID- 16610939
TI  - CACNA1C polymorphisms are associated with the efficacy of calcium channel
      blockers in the treatment of hypertension.
AB  - Retrospective pharmacogenetic analysis was performed on 120 Caucasian subjects.
      Subjects were obtained in collaboration with the Estonian Genome Project and
      Egeen Inc. (CA, USA), who provided blinded medical record and genetic data to the
      researchers, respectively. Subjects selected from the Estonian Genome Project had
      a diagnosis of hypertension confirmed by at least two blood pressure measurements
      and multiple follow-up measurements for assessing calcium channel blocker
      antihypertensive treatment outcome. Treatment outcome was scored positive if at
      least three follow-up blood pressure measurements were nonhypertensive and no
      more than one follow-up measurement was hypertensive (>140/90). The genotypes of
      62 single nucleotide polymorphisms (SNPs) in the calcium channel, voltage
      dependent, L type, alpha 1C subunit (CACNA1C) gene were obtained for each subject
      from a blood sample. Univariate analyses with multiple test correction were
      conducted using family-wise error rate and false discovery rate methods. Three
      SNPs in CANCA1C had significant associations with antihypertensive outcome,
      combining to yield a positive treatment outcome of less than 15 to 80%.

PMID- 16610940
TI  - Gene expression profiling to monitor therapeutic and adverse effects of antisense
      therapies for Duchenne muscular dystrophy.
AB  - OBJECTIVES: The objective of this study was to assess the utility of the gene
      expression profiling technique for the preclinical evaluation of drug efficacy
      and safety, taking a new therapeutic approach for Duchenne muscular dystrophy
      (DMD) as an example. METHODS: Muscles from dystrophin-deficient (mdx) mice, a
      well-characterized animal model for DMD, were injected with antisense constructs
      that restore the open reading frame in the Dmd gene. Synthetic antisense
      oligonucleotides (AONs) complexed with different carriers to enhance cellular
      uptake and recombinant adeno-associated virus (rAAV)-expressed antisense
      sequences were evaluated. Muscular gene expression profiles were analyzed on
      oligonucleotide microarrays. RESULTS: Polyethylenimine (PEI)-complexed AONs
      restored the reading frame slightly more effectively than uncomplexed, F127- or
      Optison-complexed AONs. However, PEI induced the expression of many immune genes,
      reflecting an aggravation of the inflammation present in untreated mdx mice.
      Expression profiles in Optison and F127-injected muscles were similar to those of
      saline treated muscles, implying that these carriers did not evoke adverse
      responses. Due to moderate levels of exon skipping, a significant shift toward
      wild-type expression levels was not detected. Injection with rAAV vectors
      resulted in much higher production of dystrophin and greatly improved the
      histological appearance of the muscle. Depending on the efficacy of the
      treatment, the expression of genes previously shown to be elevated in muscular
      dystrophies, partly or completely returned to wild-type expression levels.
      Reductions in inflammation and fibrosis were among the most prominent changes
      observed. CONCLUSION: Expression profiling is a powerful tool for the evaluation
      of both desired and adverse effects of new pharmacological therapies. It is
      sensitive and detects changes that are not histologically visible. In addition,
      its ability to simultaneously monitor a large number of different biological
      processes not only reduces the number of different assays required in preclinical
      research and clinical trials, but may also assist in the early detection of
      potential side effects.

PMID- 16610941
TI  - Robust statistical methods for hit selection in RNA interference high-throughput
      screening experiments.
AB  - RNA interference (RNAi) high-throughput screening (HTS) experiments carried out
      using large (>5000 short interfering [si]RNA) libraries generate a huge amount of
      data. In order to use these data to identify the most effective siRNAs tested, it
      is critical to adopt and develop appropriate statistical methods. To address the
      questions in hit selection of RNAi HTS, we proposed a quartile-based method which
      is robust to outliers, true hits and nonsymmetrical data. We compared it with the
      more traditional tests, mean +/- k standard deviation (SD) and median +/- 3
      median of absolute deviation (MAD). The results suggested that the quartile-based
      method selected more hits than mean +/- k SD under the same preset error rate.
      The number of hits selected by median +/- k MAD was close to that by the quartile
      based method. Further analysis suggested that the quartile-based method had the
      greatest power in detecting true hits, especially weak or moderate true hits. Our
      investigation also suggested that platewise analysis (determining effective
      siRNAs on a plate-by-plate basis) can adjust for systematic errors in different
      plates, while an experimentwise analysis, in which effective siRNAs are
      identified in an analysis of the entire experiment, cannot. However,
      experimentwise analysis may detect a cluster of true positive hits placed
      together in one or several plates, while platewise analysis may not. To display
      hit selection results, we designed a specific figure called a plate-well series
      plot. We thus suggest the following strategy for hit selection in RNAi HTS
      experiments. First, choose the quartile-based method, or median +/- k MAD, for
      identifying effective siRNAs. Second, perform the chosen method experimentwise on
      transformed/normalized data, such as percentage inhibition, to check the
      possibility of hit clusters. If a cluster of selected hits are observed, repeat
      the analysis based on untransformed data to determine whether the cluster is due
      to an artifact in the data. If no clusters of hits are observed, select hits by
      performing platewise analysis on transformed data. Third, adopt the plate-well
      series plot to visualize both the data and the hit selection results, as well as
      to check for artifacts.

PMID- 16610942
TI  - Visualizing gene determinants of disease in drug discovery.
AB  - Target discovery, subphenotype detection and the detection of human heterogeneity
      are major challenges in drug discovery and development on which genetic markers
      can have an impact. Visualizing gene determinants of traits in case-control study
      individuals during drug discovery using contrasts of empirically-derived log
      Bayes factors (LBFs) from whole-genome scan single nucleotide polymorphism (SNP)
      data is presented to aid this. Examples of the use of eigen analysis, covariate
      overlays and individualized aggregation to ontologies are included from disease
      research studies. Displays of individuals, or exposures of biological features of
      interest, can encompass unlimited numbers of markers in a single multivariate
      analysis without multiple testing. This filtering approach is aimed at
      nonspecialists who find themselves asked to undertake work such as that performed
      by the authors.

PMID- 16610943
TI  - A public health approach to pharmacogenomics and gene-based diagnostic tests.
AB  - While the human genome project is likely to lead to fundamental changes in our
      understanding of disease causation and our ability to screen for disease
      predisposition and treatment responsiveness, the current healthcare system is not
      properly aligned to ensure the proper use of these advances. As the pace of
      genetic technology development increases and new pharmacogenetic drugs and gene
      based diagnostic tests increasingly impact providers, patients, health plans,
      payers and employers, it will be crucial to develop an evidence-based framework
      by which to evaluate these new tests and treatments. In order to increase the
      level of evidence available and allow for informed decisions in the face of
      strong marketing and advocacy forces, the authors suggest the development of one
      (or more) large clinical networks with the purpose of systematically evaluating
      the clinical effectiveness of new genomic applications, including pharmaceuticals
      and gene-based diagnostic tests, in 'real world' settings.

PMID- 16610944
TI  - The postgenomic era and complex disease.

PMID- 16610945
TI  - The challenge of integrating disparate high-content data: epidemiological,
      clinical and laboratory data collected during an in-hospital study of chronic
      fatigue syndrome.
AB  - Chronic fatigue syndrome (CFS) is a debilitating illness characterized by
      multiple unexplained symptoms including fatigue, cognitive impairment and pain.
      People with CFS have no characteristic physical signs or diagnostic laboratory
      abnormalities, and the etiology and pathophysiology remain unknown. CFS
      represents a complex illness that includes alterations in homeostatic systems,
      involves multiple body systems and results from the combined action of many
      genes, environmental factors and risk-conferring behavior. In order to achieve
      understanding of complex illnesses, such as CFS, studies must collect relevant
      epidemiological, clinical and laboratory data and then integrate, analyze and
      interpret the information so as to obtain meaningful clinical and biological
      insight. This issue of Pharmacogenomics represents such an approach to CFS. Data
      was collected during a 2-day in-hospital study of persons with CFS, other
      medically and psychiatrically unexplained fatiguing illnesses and nonfatigued
      controls identified from the general population of Wichita, KS, USA. While in the
      hospital, the participants' psychiatric status, sleep characteristics and
      cognitive functioning was evaluated, and biological samples were collected to
      measure neuroendocrine status, autonomic nervous system function, systemic
      cytokines and peripheral blood gene expression. The data generated from these
      assessments was made available to a multidisciplinary group of 20 investigators
      from around the world who were challenged with revealing new insight and
      algorithms for integration of this complex, high-content data and, if possible,
      identifying molecular markers and elucidating pathophysiology of chronic fatigue.
      The group was divided into four teams with representation from the disciplines of
      medicine, mathematics, biology, engineering and computer science. The papers in
      this issue are the culmination of this 6-month challenge, and demonstrate that
      data integration and multidisciplinary collaboration can indeed yield novel
      approaches for handling large, complex datasets, and reveal new insight and
      relevance to a complex illness such as CFS.

PMID- 16610946
TI  - An empirical delineation of the heterogeneity of chronic unexplained fatigue in
      women.
AB  - OBJECTIVES: To test the hypothesis that medically unexplained chronic fatigue and
      chronic fatigue syndrome (CFS) are heterogeneous conditions, and to define the
      different conditions using both symptom and laboratory data. METHODS: We studied
      159 women from KS, USA. A total of 51 of these suffered from fatigue consistent
      with established criteria for CFS, 55 had chronic fatigue of insufficient
      symptoms/severity for a CFS diagnosis and 53 were healthy controls matched by age
      and body mass index (BMI) against those with CFS. We used principal components
      analyses to define factors that best described the variable space and to reduce
      the number of variables. The 38 most explanatory variables were then used in
      latent class analyses to define discrete subject groups. RESULTS: Principal
      components analyses defined six discrete factors that explained 40% of the
      variance. Latent class analyses provided several interpretable solutions with
      four, five and six classes. The four-class solution was statistically most
      convincing, but the six-class solution was more interpretable. Class 1 defined 41
      (26%) subjects with obesity and relative sleep hypnoea. Class 2 were 38 (24%)
      healthy subjects. Class 3 captured 24 (15%) obese relatively hypnoeic subjects,
      but with low heart rate variability and cortisol. Class 4 were 23 (14%) sleep
      disturbed and myalgic subjects without obesity or significant depression. The two
      remaining classes with 22 (14%) and 11 (7%) subjects consisted of the most
      symptomatic and depressed, but without obesity or hypnoea. Class 5 had normal
      sleep indices. Class 6 was characterized by disturbed sleep, with low sleep heart
      rate variability, cortisol, and sex hormones. CONCLUSION: Chronic medically
      unexplained fatigue is heterogeneous. The putative syndromes were differentiated
      by obesity, sleep hypnoea, depression, physiological stress response, sleep
      disturbance, interoception and menopausal status. If these syndromes are
      externally validated and replicated, they may prove useful in determining the
      causes, pathophysiology and treatments of CFS.

PMID- 16610947
TI  - The validity of an empirical delineation of heterogeneity in chronic unexplained
      fatigue.
AB  - OBJECTIVES: To validate a latent class structure derived empirically from a
      clinical data set obtained from persons with chronic medically unexplained
      fatigue. METHODS: The strategies utilized in this validation study included:
      recalculating latent class analysis (LCA) results varying random seeds and the
      number of initial random starting sets; recalculating LCA results by substituting
      alternate variables to demonstrate a robust solution; determining the statistical
      significance of between-class differences on disability, fatigue and demographic
      measures omitted from the data set used for LCA; cross-classifying class
      membership using established Centers for Disease Control and Prevention (CDC)
      research criteria for chronic fatigue syndrome (CFS) to compare the relative
      proportions of subjects designated CFS, chronic fatigue (not CFS) or healthy
      controls captured by the latent classes. RESULTS: Recalculation of results and
      substitution of variables for low-loading variables demonstrated a robust LCA
      result. Highly significant between-class differences were confirmed between Class
      2 (well) and those interpreted as ill/fatigued. Analysis of between-class
      differences for the fatigue groups revealed significant differences for all
      disability and fatigue variables, but with equivalent levels of reported activity
      and reduction in motivation. Cross-classification against established CDC
      criteria demonstrated that 89% of subjects constituting Class 2 (well) were
      indeed nonfatigued controls. A general tendency for grouping CFS cases in the
      multiple symptomatic classes was noted. CONCLUSION: This study established
      reasonably good validity for an empirically-derived latent class solution
      reflecting considerable heterogeneity among subjects with medically unexplained
      chronic fatigue. This work strengthens the growing understanding of CFS as a
      heterogeneous entity comprised of several conditions with different underlying
      pathophysiological mechanisms.

PMID- 16610948
TI  - Gene expression profile of empirically delineated classes of unexplained chronic
      fatigue.
AB  - OBJECTIVES: To identify the underlying gene expression profiles of unexplained
      chronic fatigue subjects classified into five or six class solutions by principal
      component (PCA) and latent class analyses (LCA). METHODS: Microarray expression
      data were available for 15,315 genes and 111 female subjects enrolled from a
      population-based study on chronic fatigue syndrome. Algorithms were developed to
      assign gene scores and threshold values that signified the contribution of each
      gene to discriminate the multiclasses in each LCA solution. Unsupervised
      dimensionality reduction was first used to remove noise or otherwise
      uninformative gene combinations, followed by supervised dimensionality reduction
      to isolate gene combinations that best separate the classes. RESULTS: The
      authors' gene score and threshold algorithms identified 32 and 26 genes capable
      of discriminating the five and six multiclass solutions, respectively. Pair-wise
      comparisons suggested that some genes (zinc finger protein 350 [ZNF350], solute
      carrier family 1, member 6 [SLC1A6], F-box protein 7 [FBX07] and vacuole 14
      protein homolog [VAC14]) distinguished most classes of fatigued subjects from
      healthy subjects, whereas others (patched homolog 2 [PTCH2] and T-cell
      leukemia/lymphoma [TCL1A]) differentiated specific fatigue classes. CONCLUSION: A
      computational approach was developed for general use to identify discriminatory
      genes in any multiclass problem. Using this approach, differences in gene
      expression were found to discriminate some classes of unexplained chronic
      fatigue, particularly one termed interoception.

PMID- 16610949
TI  - Polymorphisms in genes regulating the HPA axis associated with empirically
      delineated classes of unexplained chronic fatigue.
AB  - Chronic fatigue syndrome (CFS) is characterized by persistent or relapsing
      fatigue that is not alleviated by rest, causes substantial reduction in
      activities and is accompanied by a variety of symptoms. Its unknown etiology may
      reflect that CFS is heterogeneous. Latent class analyses of symptoms and
      physiological systems were used to delineate subgroups within a population-based
      sample of fatigued and nonfatigued subjects [1] . This study examined whether
      genetic differences underlie the individual subgroups of the latent class
      solution. Polymorphisms in 11 candidate genes related to both hypothalamic
      pituitary-adrenal (HPA) axis function and mood-related neurotransmitter systems
      were evaluated by comparing each of the five ill classes (Class 1, n = 33; Class
      3, n = 22; Class 4, n = 22; Class 5, n = 17; Class 6, n = 11) of fatigued
      subjects with subjects defined as well (Class 2, n = 35). Of the five classes of
      subjects with unexplained fatigue, three classes were distinguished by gene
      polymorphsims involved in either HPA axis function or neurotransmitter systems,
      including proopiomelanocortin (POMC), nuclear receptor subfamily 3, group C,
      member 1 (NR3C1), monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), and
      tryptophan hydroxylase 2 (TPH2). These data support the hypothesis that medically
      unexplained chronic fatigue is heterogeneous and presents preliminary evidence of
      the genetic mechanisms underlying some of the putative conditions.

PMID- 16610950
TI  - Gene expression correlates of unexplained fatigue.
AB  - Quantitative trait analysis (QTA) can be used to test whether the expression of a
      particular gene significantly correlates with some ordinal variable. To limit the
      number of false discoveries in the gene list, a multivariate permutation test can
      also be performed. The purpose of this study is to identify peripheral blood gene
      expression correlates of fatigue using quantitative trait analysis on gene
      expression data from 20,000 genes and fatigue traits measured using the
      multidimensional fatigue inventory (MFI). A total of 839 genes were statistically
      associated with fatigue measures. These mapped to biological pathways such as
      oxidative phosphorylation, gluconeogenesis, lipid metabolism, and several signal
      transduction pathways. However, more than 50% are not functionally annotated or
      associated with identified pathways. There is some overlap with genes implicated
      in other studies using differential gene expression. However, QTA allows
      detection of alterations that may not reach statistical significance in class
      comparison analyses, but which could contribute to disease pathophysiology. This
      study supports the use of phenotypic measures of chronic fatigue syndrome (CFS)
      and QTA as important for additional studies of this complex illness. Gene
      expression correlates of other phenotypic measures in the CFS Computational
      Challenge (C3) data set could be useful. Future studies of CFS should include as
      many precise measures of disease phenotype as is practical.

PMID- 16610951
TI  - Identifying illness parameters in fatiguing syndromes using classical projection
      methods.
AB  - OBJECTIVES: To examine the potential of multivariate projection methods in
      identifying common patterns of change in clinical and gene expression data that
      capture the illness state of subjects with unexplained fatigue and nonfatigued
      control participants. METHODS: Data for 111 female subjects was examined. A total
      of 59 indicators, including multidimensional fatigue inventory (MFI), medical
      outcome Short Form 36 (SF-36), Centers for Disease Control and Prevention (CDC)
      symptom inventory and cognitive response described illness. Partial least squares
      (PLS) was used to construct two feature spaces: one describing the symptom space
      from gene expression in peripheral blood mononuclear cells (PBMC) and one based
      on 117 clinical variables. Multiplicative scatter correction followed by quantile
      normalization was applied for trend removal and range adjustment of microarray
      data. Microarray quality was assessed using mean Pearson correlation between
      samples. Benjamini-Hochberg multiple testing criteria served to identify
      significantly expressed probes. RESULTS: A single common trend in 59 symptom
      constructs isolates of nonfatigued subjects from the overall group. This
      segregation is supported by two co-regulation patterns representing 10% of the
      overall microarray variation. Of the 39 principal contributors, the 17 probes
      annotated related to basic cellular processes involved in cell signaling, ion
      transport and immune system function. The single most influential gene was
      sestrin 1 (SESN1), supporting recent evidence of oxidative stress involvement in
      chronic fatigue syndrome (CFS). Dominant variables in the clinical feature space
      described heart rate variability (HRV) during sleep. Potassium and free thyroxine
      (T4) also figure prominently. CONCLUSION: Combining multiple symptom, gene or
      clinical variables into composite features provides better discrimination of the
      illness state than even the most influential variable used alone. Although the
      exact mechanism is unclear, results suggest a common link between oxidative
      stress, immune system dysfunction and potassium imbalance in CFS patients leading
      to impaired sympatho-vagal balance strongly reflected in abnormal HRV.

PMID- 16610952
TI  - Exploration of statistical dependence between illness parameters using the
      entropy correlation coefficient.
AB  - The entropy correlation coefficient (ECC) is a useful tool for measuring
      statistical dependence between variables. We employed this tool to search for
      pairs of variables that correlated in the chronic fatigue syndrome (CFS)
      Computational Challenge dataset. Highly related variables are candidates for data
      reduction, and novel relationships could lead to hypotheses regarding the
      pathogenesis of CFS. METHODS: Data for 130 female participants in the Wichita
      (KS, USA) clinical study [1] was coded into numerical values. Metric data was
      grouped using Gaussian mixture models; the number of groups was chosen using
      Bayesian information content. The pair-wise correlation between all variables was
      computed using the ECC. Significance was estimated from 1000 iterations of a
      permutation test and a threshold of 0.01 was used to identify significantly
      correlated variables. RESULTS: The five dimensions of multidimensional fatigue
      inventory (MFI) were all highly correlated with each other. Seven Short Form (SF)
      36 measures, four CFS case-defining symptoms and the Zung self-rating depression
      scale all correlated with all MFI dimensions. No physiological variables
      correlate with more than one MFI dimension. MFI, SF-36, CDC symptom inventory,
      the Zung self-rating depression scale and three Cambridge Neuropsychological Test
      Automated Battery (CANTAB) measures are highly correlated with CFS disease
      status. DISCUSSION: Correlations between the five dimensions of MFI are expected
      since they are measured from the same instrument. The relationship between MFI
      and Zung depression index has been previously reported. MFI, SF-36, and Centers
      for Disease Control and Prevention (CDC) symptom inventory are used to classify
      CFS; it is not surprising that they are correlated with disease status. Only one
      of the three CANTAB measures that correlate with disease status has been
      previously found, indicating the ECC identifies relationships not found with
      other statistical tools. CONCLUSION: The ECC is a useful tool for measuring
      statistical dependence between variables in clinical and laboratory datasets. The
      ECC needs to be further studied to gain a better understanding of its meaning for
      clinical data.

PMID- 16610953
TI  - Gene expression profile exploration of a large dataset on chronic fatigue
      syndrome.
AB  - OBJECTIVE: To gain understanding of the molecular basis of chronic fatigue
      syndrome (CFS) through gene expression analysis using a large microarray data set
      in conjunction with clinically administrated questionnaires. METHOD: Data from
      the Wichita (KS, USA) CFS Surveillance Study was used, comprising 167
      participants with two self-report questionnaires (multidimensional fatigue
      inventory [MFI] and Zung depression scale [Zung]), microarray data, empiric
      classification, and others. Microarray data was analyzed using bioinformatics
      tools from ArrayTrack. RESULTS: Correspondence analysis was applied to the MFI
      questionnaire to select the 23 samples having either the most or the least
      fatigue, and to the Zung questionnaire to select the 26 samples having either the
      most or least depression; ten samples were common, resulting in a total of 39
      samples. The MFI and Zung-based CFS/non-CFS (NF) classifications on the 39
      samples were consistent with the empiric classification. Two differentially
      expressed gene lists were determined, 188 fatigue-related genes and 164
      depression-related genes, which shared 24 common genes and involved 11 common
      pathways. Principal component analysis based on 24 genes clearly separates 39
      samples with respect to their likelihood to be CFS. Most of the 24 genes are not
      previously reported for CFS, yet their functions are consistent with the
      prevailing model of CFS, such as immune response, apoptosis, ion channel
      activity, signal transduction, cell-cell signaling, regulation of cell growth and
      neuronal activity. Hierarchical cluster analysis was performed based on 24 genes
      to classify 128 (=167-39) unassigned samples. Several of the 11 identified common
      pathways are supported by earlier findings for CFS, such as cytokine-cytokine
      receptor interaction and neuroactive ligand-receptor interaction. Importantly,
      most of the 11 common pathways are interrelated, suggesting complex biological
      mechanisms associated with CFS. CONCLUSION: Bioinformatics is critical in this
      study to select definitive sample groups, analyze gene expression data and gain
      insight into biological mechanisms. The 24 identified common genes and 11 common
      pathways could be important in future studies of CFS at the molecular level.

PMID- 16610955
TI  - Linear data mining the Wichita clinical matrix suggests sleep and allostatic load
      involvement in chronic fatigue syndrome.
AB  - OBJECTIVES: To provide a mathematical introduction to the Wichita (KS, USA)
      clinical dataset, which is all of the nongenetic data (no microarray or single
      nucleotide polymorphism data) from the 2-day clinical evaluation, and show the
      preliminary findings and limitations, of popular, matrix algebra-based data
      mining techniques. METHODS: An initial matrix of 440 variables by 227 human
      subjects was reduced to 183 variables by 164 subjects. Variables were excluded
      that strongly correlated with chronic fatigue syndrome (CFS) case classification
      by design (for example, the multidimensional fatigue inventory [MFI] data), that
      were otherwise self reporting in nature and also tended to correlate strongly
      with CFS classification, or were sparse or nonvarying between case and control.
      Subjects were excluded if they did not clearly fall into well-defined CFS
      classifications, had comorbid depression with melancholic features, or other
      medical or psychiatric exclusions. The popular data mining techniques, principle
      components analysis (PCA) and linear discriminant analysis (LDA), were used to
      determine how well the data separated into groups. Two different feature
      selection methods helped identify the most discriminating parameters. RESULTS:
      Although purely biological features (variables) were found to separate CFS cases
      from controls, including many allostatic load and sleep-related variables, most
      parameters were not statistically significant individually. However, biological
      correlates of CFS, such as heart rate and heart rate variability, require further
      investigation. CONCLUSIONS: Feature selection of a limited number of variables
      from the purely biological dataset produced better separation between groups than
      a PCA of the entire dataset. Feature selection highlighted the importance of many
      of the allostatic load variables studied in more detail by Maloney and colleagues
      in this issue [1] , as well as some sleep-related variables. Nonetheless, matrix
      linear algebra-based data mining approaches appeared to be of limited utility
      when compared with more sophisticated nonlinear analyses on richer data types,
      such as those found in Maloney and colleagues [1] and Goertzel and colleagues [2]
      in this issue.

PMID- 16610954
TI  - Exploration of the gene expression correlates of chronic unexplained fatigue
      using factor analysis.
AB  - OBJECTIVE: To identify biomarkers of chronic fatigue syndrome (CFS) and related
      disorders through analysis of microarray data, pathology test results and self
      report symptom profiles. METHOD: To empirically derive the symptom domains of the
      illnesses, factor analysis was performed on responses to self-report
      questionnaires (multidimensional fatigue inventory, Centers for Disease Control
      and Prevention (CDC) symptom inventory and Zung depression scale) before
      validation with independent datasets. Gene expression patterns that distinguished
      subjects across each factor dimension were then sought. RESULTS: A four-factor
      solution was favored, featuring 'fatigue' and 'mood disturbance' factors. Scores
      on these factors correlated with measures of disability on the Short Form (SF)
      36. A total of 57 genes that distinguished subjects along each factor dimension
      were identified, although the separation was significant only for subjects beyond
      the extreme (15th and 85th) percentiles of severity. Clustering of laboratory
      parameters with expression of these genes revealed associations with serum
      measurements of pH, electrolytes, glucose, urea, creatinine, and liver enzymes
      (aspartate amino transferase [AST] and alanine amino transferase [AST]); as well
      as hematocrit and white cell count. CONCLUSION: CFS is a complex syndrome that
      cannot simply be associated with changes in individual laboratory tests or
      expression levels of individual genes. No clear association with gene expression
      and individual symptom domains was found. However, analysis of such multifacetted
      datasets is likely to be an important means to elucidate the pathogenesis of CFS.

PMID- 16610956
TI  - Chronic fatigue syndrome and high allostatic load.
AB  - STUDY POPULATION: We examined the relationship between chronic fatigue syndrome
      (CFS) and allostatic load in a population-based, case-control study of 43 CFS
      patients and 60 nonfatigued, healthy controls from Wichita, KS, USA. METHODS: An
      allostatic load index was computed for all study participants using available
      laboratory and clinical data, according to a standard algorithm for allostatic
      load. Logistic regression analysis was used to compute odds ratios (ORs) as
      estimates of relative risk in models that included adjustment for matching
      factors and education; 95% confidence intervals (CIs) were computed to estimate
      the precision of the ORs. RESULTS: CFS patients were 1.9-times more likely to
      have a high allostatic load index than controls (95% CI = 0.75, 4.75) after
      adjusting for education level, in addition to matching factors. The strength of
      this association increased in a linear trend across categories of low, medium and
      high levels of allostatic load (p = 0.06). CONCLUSION: CFS was associated with a
      high level of allostatic load. The three allostatic load components that best
      discriminated cases from controls were waist:hip ratio, aldosterone and urinary
      cortisol.

PMID- 16610957
TI  - Combinations of single nucleotide polymorphisms in neuroendocrine effector and
      receptor genes predict chronic fatigue syndrome.
AB  - OBJECTIVE: This paper asks whether the presence of chronic fatigue syndrome (CFS)
      can be more accurately predicted from single nucleotide polymorphism (SNP)
      profiles than would occur by chance. METHODS: Specifically, given SNP profiles
      for 43 CFS patients, together with 58 controls, we used an enumerative search to
      identify an ensemble of conjunctive rules that predict whether a patient has CFS.
      RESULTS: The accuracy of the rules reached 76.3%, with the highest accuracy rules
      yielding 49 true negatives, 15 false negatives, 28 true positives and nine false
      positives (odds ratio [OR] 8.94, p < 0.0001). Analysis of the SNPs used most
      frequently in the overall ensemble of rules gave rise to a list of 'most
      important SNPs', which was not identical to the list of 'most differentiating
      SNPs' that one would calculate via studying each SNP independently. The top three
      genes containing the SNPs accounting for the highest accumulated importances were
      neuronal tryptophan hydroxylase (TPH2), catechol-O-methyltransferase (COMT) and
      nuclear receptor subfamily 3, group C, member 1 glucocorticoid receptor (NR3C1).
      CONCLUSION: The fact that only 28 out of several million possible SNPs predict
      whether a person has CFS with 76% accuracy indicates that CFS has a genetic
      component that may help to explain some aspects of the illness.

PMID- 16610958
TI  - Allostatic load is associated with symptoms in chronic fatigue syndrome patients.
AB  - OBJECTIVES: To further explore the relationship between chronic fatigue syndrome
      (CFS) and allostatic load (AL), we conducted a computational analysis involving
      43 patients with CFS and 60 nonfatigued, healthy controls (NF) enrolled in a
      population-based case-control study in Wichita (KS, USA). We used traditional
      biostatistical methods to measure the association of high AL to standardized
      measures of physical and mental functioning, disability, fatigue and general
      symptom severity. We also used nonlinear regression technology embedded in
      machine learning algorithms to learn equations predicting various CFS symptoms
      based on the individual components of the allostatic load index (ALI). METHODS:
      An ALI was computed for all study participants using available laboratory and
      clinical data on metabolic, cardiovascular and hypothalamic-pituitary-adrenal
      (HPA) axis factors. Physical and mental functioning/impairment was measured using
      the Medical Outcomes Study 36-item Short Form Health Survey (SF-36); current
      fatigue was measured using the 20-item multidimensional fatigue inventory (MFI);
      frequency and intensity of symptoms was measured using the 19-item symptom
      inventory (SI). Genetic programming, a nonlinear regression technique, was used
      to learn an ensemble of different predictive equations rather just than a single
      one. Statistical analysis was based on the calculation of the percentage of
      equations in the ensemble that utilized each input variable, producing a measure
      of the 'utility' of the variable for the predictive problem at hand. Traditional
      biostatistics methods include the median and Wilcoxon tests for comparing the
      median levels of subscale scores obtained on the SF-36, the MFI and the SI
      summary score. RESULTS: Among CFS patients, but not controls, a high level of AL
      was significantly associated with lower median values (indicating worse health)
      of bodily pain, physical functioning and general symptom frequency/intensity.
      Using genetic programming, the ALI was determined to be a better predictor of
      these three health measures than any subcombination of ALI components among
      cases, but not controls.

PMID- 16610959
TI  - Improved prediction of treatment response using microarrays and existing
      biological knowledge.
AB  - A desired application for microarrays in the clinic is to predict treatment
      response from an often diverse patient population. We present a method for
      analyzing microarray data that is predicated on biological pathway and function
      knowledge as opposed to a purely data-driven initial analysis. From an analysis
      perspective, this methodology takes advantage of information that is available
      across genes on a single array, as well as differences in those patterns across
      measurements. By using biological knowledge in the initial analysis, the accuracy
      and robustness of microarray profile classification is enhanced, especially when
      low numbers of samples are available. For clinical studies, particularly Phase I
      or I/II studies, this technique is exceptionally advantageous.

PMID- 16610960
TI  - Interpreter of maladies: redescription mining applied to biomedical data
      analysis.
AB  - Comprehensive, systematic and integrated data-centric statistical approaches to
      disease modeling can provide powerful frameworks for understanding disease
      etiology. Here, one such computational framework based on redescription mining in
      both its incarnations, static and dynamic, is discussed. The static framework
      provides bioinformatic tools applicable to multifaceted datasets, containing
      genetic, transcriptomic, proteomic, and clinical data for diseased patients and
      normal subjects. The dynamic redescription framework provides systems biology
      tools to model complex sets of regulatory, metabolic and signaling pathways in
      the initiation and progression of a disease. As an example, the case of chronic
      fatigue syndrome (CFS) is considered, which has so far remained intractable and
      unpredictable in its etiology and nosology. The redescription mining approaches
      can be applied to the Centers for Disease Control and Prevention's Wichita (KS,
      USA) dataset, integrating transcriptomic, epidemiological and clinical data, and
      can also be used to study how pathways in the hypothalamic-pituitary-adrenal axis
      affect CFS patients.

PMID- 16610961
TI  - Statistical challenges with gene expression studies.
AB  - Studies that include high-throughput data, such as gene expression data, raise
      unique issues with respect to study design and analysis. At the same time, they
      should be viewed through the lens (albeit a modified one) of standard scientific
      approach that involves such issues as specifying objectives (even if the study is
      mainly hypothesis generating or exploratory), a careful consideration of design,
      including sample size and replication, deciding whether to include technical
      replication in addition to biological replication, and ensuring that the methods
      of analysis are appropriate for the objective.

PMID- 16610962
TI  - Clinical methodology and its implications for the study of therapeutic
      interventions for chronic fatigue syndrome: a commentary.
AB  - Chronic fatigue syndrome (CFS) is a complex, multisymptom illness of unknown
      etiology. A variety of operational case definitions based on symptom report have
      been developed that share some common clinical features. Patients often come to
      clinical presentation after months or, more typically, years of symptomatic
      distress. Comorbid presentation with psychiatric illnesses has been noted. Due to
      these fundamental issues, the impact of patient selection and the specification
      of the methods of outcome assessment loom large in therapeutic studies of CFS.
      While a substantial body of research has focused on increasing our understanding
      of the basic pathobiology of CFS, there have been comparatively fewer studies
      that have addressed the problems of patient characterization and outcome
      assessment. The role of clinical methodology in the study of the therapeutics of
      CFS is not trivial, and may confound our understanding of pragmatic
      recommendations for treatment.

PMID- 16610964
TI  - Safety and side effects of the insulin analogues.

PMID- 16610965
TI  - Combination conjugate vaccines.
AB  - Increasingly, more diseases are becoming vaccine preventable, but maintaining
      community and provider acceptance demands that the number of injections does not
      increase. Combination conjugate vaccines represent an inevitable and important
      advance. This paper reviews the efficacy and safety of combination conjugate
      vaccines, including immunological mechanisms underlying interactions among
      vaccine epitopes, the role of immunological memory, and correlates of immunity.
      Specific attention is given to the experience with combination vaccines against
      each of Haemophilus influenzae type b, Streptococcus pneumoniae and Neisseria
      meningitidis. The implications of these findings for different communities are
      discussed, key areas for further research identified and implications for post
      licensure monitoring addressed.

PMID- 16610966
TI  - Antibiotic-associated diarrhoea.
AB  - Diarrhoea is a common complication of antimicrobial therapy. The term antibiotic
      associated diarrhoea (AAD) is often considered synonymous with Clostridium
      difficile. In fact, AAD can develop through a variety of mechanisms and manifest
      through a broad range of clinical signs and symptoms. For improved prevention and
      recognition of AAD, it is important to understand the pathophysiology and risk
      factors for AAD. Although Clostridium difficile continues to be the most common
      identifiable pathogen of AAD, many patients with AAD can be managed through a
      variety of conservative measures. This review focuses on some of the important
      distinctions between nonspecific AAD and antibiotic-associated colitis. In
      addition, the most recent data on important risk factors for the development of
      AAD are summarised. Given its pathogenicity, there will be an emphasis on the
      early diagnosis, treatment and prevention of Clostridium difficile-associated
      diarrhoea. AAD is a common clinical problem that can progress to severe, life
      threatening disease if not recognised quickly. Better awareness of risk factors
      can lead to the most efficacious treatment of this disorder: primary prevention.

PMID- 16610967
TI  - Mitochondrial disease in the offspring as a result of antiretroviral therapy.
AB  - Nucleoside analogue reverse transcriptase inhibitors (NRTIs) have substantially
      lowered the risk of the mother-to-child transmission of HIV. Evidence of
      mitochondrial toxicity in vitro, in animal models and in adult HIV-infected
      patients, has raised concern about the perinatal safety of these antiretrovirals.
      In zidovudine-exposed, but HIV-uninfected infants, transient anaemia and
      additional long-term blood abnormalities (neutropenia, thrombopenia and
      lymphopenia) and hyperlactatemia have been documented. The overall risk of
      mortality and congenital abnormalities does not appear to be increased, but rare
      mitochondrial events cannot be excluded for lack of statistical power. French
      data suggest an above background incidence of mitochondrial symptomatology.
      Preclinical data demonstrate zidovudine also to be a carcinogen. Long-term
      systematic follow-up of exposed babies in large cohorts is needed, as are
      randomised trials with NRTIs carrying a lower risk of mitochondrial toxicity.

PMID- 16610968
TI  - Understanding drug ototoxicity: molecular insights for prevention and clinical
      management.
AB  - Ototoxicity is a trait shared by aminoglycoside and macrolide antibiotics, loop
      diuretics, platinum-based chemotherapeutic agents, some NSAIDs and antimalarial
      medications. Because their benefits in combating certain life-threatening
      diseases often outweigh the risks, the use of these ototoxic drugs cannot simply
      be avoided. In this review, the authors discuss some of the most frequently used
      ototoxic drugs and what is currently known about the cell and molecular
      mechanisms underlying their noxious effects. The authors also provide suggestions
      for the clinical management of ototoxic medications, including ototoxic detection
      and drug monitoring. Understanding the mechanisms of drug ototoxicity may lead to
      new strategies for preventing and curing drug-induced hearing loss, as well as
      developing new pharmacological drugs with less toxic side effects.

PMID- 16610969
TI  - Safety and tolerability of mood-stabilising anticonvulsants in the elderly.
AB  - The authors review current research on the safety and tolerability of
      anticonvulsant medications used for individuals over the age of 60 years with
      affective disorders, agitation and other psychiatric disorders. Three
      anticonvulsants currently approved in the US for treatment of bipolar affective
      disorder are reviewed: valproate, lamotrigine and extended-release carbamazepine.
      The authors discuss the pharmacokinetics, pharmacodynamics, drug-drug
      interactions and the impact of ageing for each drug. There are few studies of
      anticonvulsant medications in elderly patients with bipolar disorder or other
      psychiatric conditions. Therefore, the authors summarise adverse events of
      greatest prevalence and/or greatest severity based on data derived predominately
      from studies of geriatric patients with epilepsy and/or other non-psychiatric
      indications. Guidelines are offered for the safe use of these medications in the
      elderly, based on research literature.

PMID- 16610970
TI  - The risks of warfarin use in the elderly.
AB  - The use of warfarin in the elderly, particularly for stroke prevention in chronic
      atrial fibrillation, is steadily increasing. Although the benefits of warfarin
      are greatest in the elderly, so are the risk of adverse outcomes and the
      difficulties of anticoagulant management. Clinical systems need to improve to
      counter this therapeutic dilemma, as warfarin is likely to remain the only widely
      available oral anticoagulant for the foreseeable future. Aspects that require
      attention are: the careful selection of patients in whom treatment with warfarin
      is appropriate; initiating therapy in a low dose (e.g., 2.5-5 mg/day); thorough
      education of patients and carers; close monitoring, especially with any change in
      the patient's regular drug therapy; involving patients more in the management of
      their warfarin therapy (self-monitoring/management in suitable patients); and
      ongoing review of the appropriateness of therapy as circumstances change.

PMID- 16610971
TI  - Warfarin and its interactions with foods, herbs and other dietary supplements.
AB  - Despite its complex pharmacokinetic and pharmacodynamic profile, warfarin is
      still one of the most widely used oral anticoagulant agents. Attaining optimal
      anticoagulation with this agent is clinically challenging in view of its many
      food and drug interactions. Inappropriate anticoagulation control can expose
      patients to an increased risk of bleeding or thromboembolic complications, due to
      over and underanticoagulation, respectively. Fluctuations in dietary vitamin K
      intake can have a significant effect on the degree of anticoagulation in patients
      treated with warfarin. In addition, the explosion in use of various dietary
      supplements and herbal products can lead to undesired outcomes on anticoagulant
      levels. The aim of this review is to discuss the scope and the potential clinical
      impact of the most commonly reported food, dietary supplement and herbal
      interactions with warfarin therapy. Practical steps for patients and providers to
      minimise these interactions are highlighted.

PMID- 16610972
TI  - The safety of digoxin as a pharmacological treatment of atrial fibrillation.
AB  - Digoxin has traditionally been the drug of choice for ventricular rate control in
      patients with chronic atrial fibrillation (AF), with or without heart failure
      (HF) with systolic dysfunction. In patients with permanent AF, digoxin
      monotherapy is ineffective to control ventricular rate during exercise, but the
      combination of digoxin with a beta-blocker or a non-dihydropyridine calcium
      channel antagonist can control heart rate both at rest and during exercise. Only
      a few randomised, controlled studies have evaluated the adverse effects of
      digoxin in patients with AF in a systematic way and side effects requiring drug
      withdrawal have rarely been reported. When reported, the most frequent adverse
      effects were cardiac arrhythmias (ventricular arrhythmias, AV block of varying
      degrees and sinus pauses). This evidence suggested that, in contrast to other
      antiarrhythmic drugs, digoxin is a safe drug in patients with AF. However, this
      safety profile can be erroneous due to the short follow-up of the studies and
      patient selection. Because patients with HF have been excluded in most studies,
      the safety profile of digoxin in this population has not been directly addressed.
      Early recognition that an arrhythmia is related to digoxin intoxication as well
      as recognition of concomitant medications or medical conditions that may directly
      alter the pharmacokinetic profile of digoxin, or indirectly alter its cardiac
      effects by pharmacodynamic interactions remain essential for safe and effective
      use of digoxin in patients with AF.

PMID- 16610973
TI  - Gefitinib: an adverse effects profile.
AB  - Gefitinib, an epidermal growth factor receptor inhibitor, is currently approved
      for use in patients with advanced non-small cell lung cancer who have failed
      previous chemotherapy or who are not suitable for chemotherapy in > 30 countries.
      The approved dose in patients with non-small cell lung cancer is 250 mg/day. The
      most common adverse effects are rash, diarrhoea, acne, dry skin, nausea and
      vomiting. Most of the effects are mild-to-moderate in nature and do not require
      discontinuation of therapy. The severity of many of these effects is dose-related
      with grade 3-4 effects more likely at a dose > 250 mg/day. The most severe
      adverse effect is interstitial lung disease (ILD), which occurs in approximately
      1% of patients worldwide except for Japan where the incidence of ILD is 2%. ILD
      is fatal in approximately one out of three of the cases. The most common adverse
      effects associated with chemotherapy, myelosuppression and alopecia, are not
      commonly seen with gefitinib monotherapy.

PMID- 16610974
TI  - Stem cells for the ischaemic heart.
AB  - The discovery of adult progenitor cells capable of generating new vascular and
      myocardial tissue offers the promise of salvage of ischaemically threatened or
      irreversibly damaged cardiac tissue. Not surprisingly, great interest has focused
      on the use of a variety of cell types to treat both acute myocardial infarction
      and chronic ischaemic heart disease. This review focuses on the treatment of
      these two categories of disease, the cell types being considered, our
      understanding of timing and methods of cellular administration, and possible
      mechanisms of myocardial salvage.

PMID- 16610975
TI  - Transplantation of cultured progenitor cells to the mammalian retina.
AB  - Multipotent progenitor cells have now been isolated from the brain and retina,
      expanded in culture, and transplanted to the central nervous system (CNS). Work
      in rodent models has shown that progenitor cells derived from the CNS readily
      engraft in the diseased retina of mature recipients, where they develop
      morphologies appropriate to the local microenvironment and express mature
      markers, including the photoreceptor protein rhodopsin. There is also evidence
      for graft-associated rescue of host photoreceptors and preservation of light
      sensitivity in the degenerating retina. Graft survival does not necessarily
      require immune suppression, as CNS progenitors can behave as an immunoprivileged
      cell type. The use of biodegradable polymers results in an organised implant and
      further improves graft survival. Efforts are underway at present to extend this
      work to the pig, with initial results showing engraftment in both the neural
      retina and retinal pigment epithelium (RPE).

PMID- 16610976
TI  - The logics of leukocytapheresis as a natural biological therapy for inflammatory
      bowel disease.
AB  - Ulcerative colitis (UC) and Crohn's disease (CD) are debilitating idiopathic
      inflammatory bowel diseases (IBDs) with symptoms that impair ability to function
      and quality of life. The aetiology of IBD is inadequately understood and,
      therefore, drug therapy has been empirical instead of based on sound
      understanding of the disease mechanisms. This has been a major factor for poor
      drug efficacy and treatment-related side effects that often add to disease
      complications. The development of biologicals, notably infliximab, to block TNF
      alpha reflects some progress, but there is major concern about their side effects
      and lack of long-term safety and efficacy profiles. However, IBD by its very
      nature is exacerbated and perpetuated by inflammatory cytokines, including TNF
      alpha, IL-6 and IL-12, for which activated peripheral blood lymphocytes,
      monocytes/macrophages and granulocytes are major sources. Hence, activated
      leukocytes should be appropriate targets of therapy. At present, three strategies
      are available for removing excess and activated leukocytes by leukocytapheresis:
      centrifugation, Adacolumn and Cellsorba. Centrifugation can deplete lymphocytes
      or total leukocytes, whereas Adacolumn selectively adsorbs granulocytes and
      monocytes together with a smaller fraction of lymphocytes (FcgammaR- and
      complement receptor-bearing leukocytes), and Cellsorba non-selectively removes
      all three major leukocyte populations. Efficacy has ranged from 'none' to an
      impressive 93% together with excellent safety profiles and downmodulation of
      inflammation factors. Furthermore, leukocytapheresis has shown strong drug
      sparing effects and reduced the number of patients requiring colectomy or
      exposure to unsafe immunosuppressants, such as cyclosporin A. Leukocytapheresis
      removes from the body cells that contribute to IBD and, therefore, unlike drugs,
      it is not expected to induce dependency or refractoriness.

PMID- 16610977
TI  - Biological response modifiers as adjuncts to stem cell transplantation.
AB  - Cytokines produced by immune and non-immune cells serve as potent mediators with
      the properties of signal cells that coordinate the immune response. They are
      delivered by cells either to the systemic circulation or to the local
      environment. They are being used at present in the field of stem cell
      transplantation (SCT) in order to improve transplant outcome. This paper reviews
      the existing data on pre-, peri- and post-SCT treatment with cytokines.

PMID- 16610978
TI  - Biodegradable scaffolds--delivery systems for cell therapies.
AB  - The use of cells as therapies for disease, repair and regeneration of tissues is
      one of the new challenges in modern therapeutics. To facilitate the ability to
      localise, condition and protect cells, biodegradable scaffolds are being
      developed that will improve the efficiency of these treatments. Thus, cell
      delivery systems, either scaffolds or capsules, play a pivotal role in the
      success of these techniques. This review discusses these novel approaches. The
      selection of scaffold materials is addressed alongside issues of
      biocompatibility. The current research developments in smart scaffolds, which
      focus on the formation of biomimetic scaffolds, new fabrication techniques
      capable of controlling architecture and microstructure of scaffolds, and the
      production of injectable and in situ crosslinked scaffolds, are outlined.
      Finally, the continuing challenges that will drive future research in the cell
      therapies are highlighted.

PMID- 16610979
TI  - Gene therapy for the treatment of sensory neuropathy.
AB  - Sensory polyneuropathy can be a serious problem, but for the majority of
      clinically important neuropathies there are no available therapies. Neurotrophic
      and neuroprotective peptide factors have been identified that prevent or reverse
      neuropathy in rodent models of disease, but delivery of these highly pleiotropic
      peptides has posed an obstacle for translation into effective human therapies.
      Gene transfer into muscle using viral or non-viral vectors, or into neurons of
      the dorsal root ganglion using herpes simplex virus-based vectors, provides an
      alternative means to achieve this end. Studies in animal models have been
      promising, and the first human trial, using a plasmid to transfer the gene coding
      for vascular endothelial growth factor into muscle for the treatment of diabetic
      neuropathy, is now underway. Evidence supporting the trial and the challenges
      facing this therapy are reviewed.

PMID- 16610980
TI  - Gene therapy for treatment of inherited haematological disorders.
AB  - Gene therapy, a molecular medicine based on vector-mediated transfer of
      therapeutic genes, holds promise for a cure of monogenetic inherited diseases. In
      recent years, tremendous progress has been reported in the treatment of
      haematological disorders: clinical trials in severe combined immune deficiencies
      have been successful by using retroviral vectors to express target genes in
      haematopoietic stem cells, which after transplantation efficiently reconstituted
      the immune system concomitant with substantial improvement in the clinical status
      of patients. Conversely, unexpected adverse events were also encountered. In
      other work, progress towards clinical studies on ex vivo gene transfer for
      Fanconi anaemia and haemoglobinopathies has been made. Each approach features a
      unique treatment strategy and also faces various impediments to success. In the
      case of the X-linked bleeding disorder haemophilia, several Phase I/II clinical
      trials were conducted, including in vivo administration of viral vectors to
      skeletal muscle and liver. Adeno-associated viral gene transfer of coagulation
      Factor IX has been documented in human subjects, reaching therapeutic levels
      after infusion into a hepatic blood vessel. However, sustained expression of
      therapeutic levels (as shown in large animal models of haemophilia) has not yet
      been achieved in humans. In general, long-term follow-up will be important for
      assessment of the safety of all existing gene therapy strategies.

PMID- 16610981
TI  - Antibody-based inhibitors of HIV infection.
AB  - The demand for new treatment options against HIV is becoming increasingly
      desperate as the side effects and the expansion and spread of drug-resistant
      virus within the infected population limit the clinical benefits provided by
      available anti-HIV drugs. Preparations of polyclonal antibodies have a long
      history of proven clinical utility against some viruses; however, they have
      enjoyed very limited success against HIV. Recent clinical trials and in vitro
      experiments suggest that monoclonal antibodies against HIV may have promise
      clinically. These antibodies and antibody-based reagents target either the viral
      envelope glycoprotein, the receptor (CD4) or coreceptor (CCR5) molecules, or
      transition-state structures that appear during viral entry. The challenge is
      whether an antibody-based therapy can be identified (with or without their small
      molecule brethren) that presents long-term clinical efficacy, low toxicity and
      minimal risk of clinical failure from viral resistance.

PMID- 16610982
TI  - Efficacy and safety of mecasermin rinfabate.
AB  - There has been interest in using recombinant human (rh) insulin-like growth
      factor (IGF)-I (rhIGF-I) to treat short stature, either alone or in combination
      with its binding protein (insulin-like growth factor binding protein [IGFBP]-3).
      IGF-I has been shown to increase growth velocity in children with IGF deficiency,
      either as a result of growth hormone insensitivity syndrome (GHIS) or IGF gene
      deletion. However, there have been adverse events, particularly hypoglycaemia,
      reported with administration of unbound rhIGF-I. In addition, the serum half-life
      of unbound rhIGF-I is shorter when administered to patients with GHIS, who have
      low serum concentrations of its binding proteins IGFBP-3 and acid-labile subunit
      (ALS), than when administered to normal volunteers or to the patient with an IGF
      I gene deletion (who had normal levels of IGFBP-3). iPlex (mecasermin rinfabate),
      an equimolar mixture of IGF-I and its binding protein IGFBP-3, was developed to
      prolong the half-life and to counteract acute adverse events (particularly
      hypoglycaemia) associated with administration of IGF-I. Although there are no
      published data on the efficacy of mecasermin rinfabate in treating growth
      disorders, it does appear that mecasermin rinfabate has a longer half-life in
      patients with GHIS than unbound IGF-I, and fewer reports of adverse events
      (including hypoglycaemia) when administered to patients with diabetes.

PMID- 16610983
TI  - (131)I-chTNT-1/B mAb: tumour necrosis therapy for malignant astrocytic glioma.
AB  - Treatment of malignant glioma is therapeutically challenging. Despite
      improvements in neurosurgery, radiotherapy and chemotherapy, few patients
      diagnosed with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) (WHO
      grades 3 and 4, respectively) will live beyond 2 years. Poor survival is due to
      the highly invasive nature and protected location of these tumours. Most
      malignant gliomas cannot be completely resected or irradiated due to their
      ability to infiltrate diffusely into normal brain tissue. Brain tissue is
      protected from the systemic circulation via the blood-brain barrier (BBB), which
      impedes entry of water-soluble chemotherapeutic agents into the tumour at
      therapeutic concentrations. (131)I-chTNT-1/B mAb (Cotara) employs an innovative
      strategy to treat the invasive portion of the tumour and the core lesion. (131)I
      chTNT-1/B mAb is a genetically engineered, radiolabelled, chimeric monoclonal
      antibody specific for a universal intracellular antigen (i.e., DNA/histone H1
      complex) exposed in the necrotic core of malignant gliomas. This antigen provides
      an abundant, insoluble, non-diffusible anchor for the mAb. Once localised to
      necrotic regions of the tumour, (131)I-chTNT-1/B mAb delivers a cytotoxic dose of
      (131)I radiation to the core lesion. (131)I-chTNT-1/B mAb is delivered via
      convection-enhanced delivery in order to maximise coverage to the tumour and the
      invasive front of the glial tumour. The clinical experience to date with (131)I
      chTNT-1/B mAb is presented.

PMID- 16610984
TI  - Bispectral index and intensive care--an alluring concept.

PMID- 16610985
TI  - Blunt abdominal trauma--how should we investigate a "kick in the guts"?

PMID- 16610987
TI  - Osmotherapy in traumatic brain injury--overused and dangerous.

PMID- 16610986
TI  - Are there any evidence-based indications for the use of mannitol in acute tubular
      necrosis?

PMID- 16610988
TI  - Intraoperative mannitol does not prevent renal failure in orthotopic liver
      transplantation.
AB  - OBJECTIVE: To undertake a prospective randomised controlled study to investigate
      whether there is any beneficial renal effect in the perioperative administration
      of mannitol in patients undergoing orthotopic liver transplantation. METHODS:
      Patients presenting in end-stage liver failure for orthotopic liver
      transplantation had their preoperative renal function assessed by 24 hour urinary
      creatinine clearance. In a randomised double-blind study they were allocated to
      receive either mannitol 0.5 g/kg intravenously, or an equivalent volume of 0.9%
      saline, after induction. All patients had central venous, peripheral and
      pulmonary artery catheters inserted and received intravenous fluids, blood and
      blood products based on central pressure measurements, thromboelastographic
      monitoring, and blood biochemistry. All patients also received intravenous
      dopamine 2.5-3.0 microg/kg/min. Intravenous fluids and urine production were
      recorded intraoperatively and for the first 24 hours in intensive care. RESULTS:
      Twenty five patients were enrolled, 13 in the control group and 12 in the
      mannitol group. There was no significant difference in the preoperative
      creatinine clearances (control group 72.1 +/- 24.5 mL/min; mannitol group 65.1 +/
      33 mL/min, p = 0.45), total intraoperative fluid requirements (control group
      10,741 +/- 4517 mL; mannitol group 13,852 +/- 11,827 mL, p = 0.38) or
      intraoperative urine production (control group 1323 +/- 1419 mL; mannitol group
      912 +/- 493 mL, p = 0.35). CONCLUSIONS: We conclude that intraoperative mannitol
      does not help preserve renal function in the patient undergoing liver
      transplantation.

PMID- 16610989
TI  - Partial liquid ventilation compared with conventional mechanical ventilation in
      an experimental model of acute lung injury.
AB  - OBJECTIVE: To compare the effects of partial liquid ventilation with conventional
      mechanical ventilation on oxygenation and pulmonary mechanics in saline lavaged
      rabbits. METHODS: Following acute lung injury (saline-lavage), rabbits were
      assigned to continue conventional mechanical ventilation (n = 6) or commence
      partial liquid ventilation (n = 6). In both groups the inspired oxygen
      concentration was 100% throughout the study. The target PaCO2 of 40-60 mmHg was
      accomplished by keeping the tidal volume between 7 and 10 mL/kg. During the study
      the peak inspiratory pressure was adjusted to maintain the target PaCO2. Arterial
      blood gases were taken pre-lavage, immediately post-lavage (time = 0) and then
      hourly for 5 hours. Pulmonary mechanics were estimated by measuring compliance
      and resistance. Pulmonary function was measured pre-lavage, immediately post
      lavage and at 1 and 5 hours. At 5 hours the rabbits were killed and the lungs
      were removed for histological examination. RESULTS: Baseline PaO2, compliance and
      resistance were not significantly different between groups. The partial liquid
      ventilation group had a higher PaO2 and a significantly better oxygenation index
      one hour after commencing partial liquid ventilation and a significantly higher
      PaO2 averaged over the three hours post-treatment. There were no significant
      differences in compliance, resistance or lung damage scores. CONCLUSIONS: In this
      experimental model of acute lung injury, partial liquid ventilation resulted in
      immediate and sustained increase in PaO2 over 3 hours without significant change
      in lung mechanics or histological lung damage.

PMID- 16610990
TI  - Sleep patterns in intensive care unit patients: a study using the bispectral
      index.
AB  - OBJECTIVE: To objectively record sleep patterns in intensive care unit patients
      using the Bispectral Index as an electroencephalographic measure of sleep and to
      determine if the sleep pattern is correlated with various clinical factors.
      METHODS: Adult intensive care patients were recruited who were in the recovery
      phase of their illness and on minimal sedation. The sleep pattern was examined
      using an overnight recording of the patient's Bispectral Index and submental
      electromyogram. RESULTS: Twenty-seven adult patients in a tertiary level general
      intensive care unit were enrolled. The sleep pattern was examined using an
      overnight recording of the patient's Bispectral Index and submental
      electromyogram. No intensive care unit patients showed a completely normal sleep
      pattern, but about half showed 40-90 min cyclical periods of slow wave sleep that
      approached a normal sleep pattern. CONCLUSIONS: Traditional classifications of
      EEG sleep staging are deficient when used to describe sleep in intensive care
      unit patients.

PMID- 16610991
TI  - Peritoneal lavage cell count ratio in blunt abdominal trauma--a useful tool in
      hollow viscus injury?
AB  - A 40-year-old man suffered severe orthopaedic and maxillo-facial injuries in a
      motor vehicle accident. After resuscitation he underwent extensive orthopaedic
      surgery to manage his fractures. A diagnostic peritoneal lavage just prior to his
      operation revealed a red blood cell count of 0.15 x 10(12)/L and white blood cell
      count of 3.3 x 10(12)/L. However, as the patient was haemodynamically stable, a
      non-operative approach was adopted. Despite a normal abdominal ultrasound, near
      normal abdominopelvic computed tomography, haemodynamic stability and tolerance
      of enteral feeding, the patient suffered a delayed sigmoid colonic perforation
      eight days after the initial trauma. While abdominal computed tomography has
      replaced diagnostic peritoneal lavage in evaluation of blunt abdominal trauma,
      this case highlights the need for a more effective tool for diagnosing hollow
      viscus injury. In this regard, the peritoneal lavage cell count ratio (which in
      retrospect in our patient indicated hollow viscus injury) may be useful.

PMID- 16610992
TI  - Isolated ventricular septal defect secondary to low-velocity blunt chest trauma.
AB  - Damage to the ventricular septum resulting from low velocity blunt trauma to the
      anterior chest wall is a rarely reported disorder. We wish to report a case of an
      isolated large ventricular septal defect secondary to blunt chest trauma
      requiring urgent surgical repair in an otherWise healthy 19 year old male. The
      patient endured a long hospital stay complicated by repeated episodes of
      pulmonary oedema and ARDS but eventually made a good recovery.

PMID- 16610993
TI  - Extracorporeal membrane oxygenation in the management of severe thoracic trauma:
      a case report.
AB  - We describe a case where extracorporeal membrane oxygenation was used for seven
      days to facilitate surgery and respiratory therapy in a multi-trauma patient with
      severe pulmonary contusions, bilateral bronchopleural fistulae with recurrent
      pneumothoraces. The patient made a good recovery and was discharged from hospital
      after three months.

PMID- 16610994
TI  - Cardiac arrest: a late complication of glucose-insulin-potassium (GIK) therapy.
AB  - Rebound hyperkalaemia 4 hours after discontinuation of a glucose-insulin
      potassium infusion inhibited an already compromised conduction system leading to
      ventricular standstill in a 41 year old man after re-do aortic valve surgery.
      Resuscitation was successful and allowed him to return from Australia to his home
      on Christmas Island. Glucose-insulin-potassium (GIK) infusions to reduce
      myocardial hypo-/re-perfusion injury after myocardial infarction, during coronary
      artery surgery and cardiopulmonary bypass are becoming more popular. There may
      also be a role for GIK in the treatment of refractory dysrhythmias and for
      myocardial protection in the brain-dead patient. However, these infusions are not
      without hazard and this report of rebound hyperkalaemia and cardiac arrest is
      unlikely to remain isolated.

PMID- 16610995
TI  - Acute gastrointestinal bleeding: Part I.
AB  - OBJECTIVE: To review the management of acute gastrointestinal bleeding in the
      critically ill patient in a two part presentation. DATA SOURCES: Articles and a
      review of studies reported from 1991 to 2001 and identified through a MEDLINE
      search of the English language literature on acute gastrointestinal bleeding.
      SUMMARY OF REVIEW: Gastrointestinal bleeding is a relatively frequent problem in
      the critically ill patient. Common causes include acute stress ulceration (ASU),
      peptic ulceration and bleeding oesophageal varices. Non-variceal upper
      gastrointestinal bleeding requires resuscitation and correction of coagulation
      disturbances before endoscopy is performed. If a bleeding ulcer is detected it is
      often managed by an adrenaline injection or electrocautery into the base of the
      lesion and a proton pump inhibitor (e.g. omeprazole 80 mg i.v. followed by 8
      mg/hr for 72 hr then 20 mg orally for 8 weeks). Surgery is considered for all
      patients in whom bleeding persists despite endoscopic or medical therapy. While
      H(2) receptor antagonists have been used for the management of ASU, proton pump
      inhibitors are currently prescribed due to their greater gastric acid suppressant
      effect (e.g. omeprazole 40 mg i.v. daily for ASU prophylaxis, 40 mg daily or 12
      hourly for ASU with mild blood loss and 80 mg i.v. followed by 8 mg/hr for 72 hrs
      for ASU with severe haemorrhage). With severe haemorrhage, fibrinolytic
      inhibitors (e.g. tranexamic acid 3-6 g i.v. daily) may also be of benefit. For
      lower gastrointestinal bleeding or if there is no obvious upper gastrointestinal
      lesion during endoscopy, then selective mesenteric angiography with embolisation
      of the bleeding point (if the bleeding is brisk, e.g. > 0.5-2.0 mL/min) or
      colonoscopy with electrocautery or adrenaline injection (for diverticular
      haemorrhage) may be considered as an alternative to surgery. CONCLUSIONS: Acute
      upper gastrointestinal bleeding is often managed by intravenous proton pump
      inhibitors and endoscopy with electrocautery or adrenaline injection when a
      bleeding at the base of an ulcer is found. For lower gastrointestinal
      haemorrhage, selective mesenteric angiography with embolisation of the bleeding
      point is an alternative to surgery in critically ill patients. Fibrinolytic
      inhibitors may have added benefit.

PMID- 16610996
TI  - Acute gastrointestinal bleeding: Part II.
AB  - OBJECTIVE: To review the management of acute gastrointestinal bleeding in the
      critically ill patient in a two part presentation. DATA SOURCES: Articles and a
      review of studies reported from 1991 to 2001 and identified through a MEDLINE
      search of the English language literature on acute gastrointestinal bleeding.
      SUMMARY OF REVIEW: Oesophageal varices are a common source of upper
      gastrointestinal bleeding in patients who have portal hypertension. Management
      requires resuscitation and treatment of associated coagulation disturbances along
      with intravenous octreotide (50 microg followed by 50 microg/hr for 48 hr) before
      endoscopy is performed. Octreotide is more effective than vasopressin in
      controlling acute variceal suppressant and has fewer side effects compared with
      glypressin. To provide haemostasis, endoscopic variceal sclerosis has largely
      been replaced by variceal ligation using an overtube and small elastic 'o' rings
      to band the bleeding variceal channels. If bleeding continues then Balloon
      tamponade and intravenous fibrinolytic inhibitors (e.g. tranexamic acid 3-6 g
      i.v. daily) are used for 24 hr before endoscopy (with variceal ligation) is
      repeated. If the variceal bleeding is resistant to repeated banding, portal
      decompression using transjugular intrahepatic portosystemic shunt or surgical
      shunt should be considered. While beta adrenergic blockers (e.g. propranalol) are
      indicated to reduce the incidence of rebleeding, they are contraindicated in a
      patient with actively bleeding oesophageal varices. CONCLUSIONS: Acute
      oesophageal variceal bleeding can often be managed successfully using octreotide
      and variceal ligation. If bleeding continues then transjugular intrahepatic
      portosystemic shunt or surgical shunt should be considered.

PMID- 16610998
TI  - An 80 year old man with a five day history of vomiting, renal failure and
      jaundice.

PMID- 16611000
TI  - Vaccine delivery--current trends and future.
AB  - Since its discovery in 1796 by Edward Jenner, vaccines have been an integral
      aspect of therapeutics, combating a number of infectious diseases with remarkable
      success. In recent years, due to rapid advances in proteomics, genomics,
      biotechnology and immunology and the plethora of knowledge amassed in related
      fields, it is fair to expect vaccine development to progress at an exponential
      pace. However, as we march on into the 21st century, we are still struggling in
      our efforts to eradicate fatal diseases such as AIDS, malaria and hepatitis C
      due, in part, to the absence of effective vaccines against these diseases.
      Vaccine development faces major challenges both technologically and economically.
      Newer vaccines that are stable, economical, require fewer doses and can be
      administered using needle free systems are a worldwide priority. An ideal
      theoretical vaccine may not be cogent unless formulated and delivered aptly.
      Delivery of vaccines via oral, intranasal, transcutaneous and intradermal routes
      will decrease the risk of needle-borne diseases and may eliminate the need for
      trained personnel and sterile equipment. Crucial to the success of a vaccine is
      the delivery strategy that is to be employed. Currently, various techniques
      involving DNA vaccines, adjuvants, microparticles and transgenic plants are being
      developed and evaluated. Although, no major breakthrough is in prospect, these
      systems have potential and will take immunization to a new technological level.
      This review will focus on the current development of some novel vaccine delivery
      systems and will explore the non-parenteral routes of vaccine administration.

PMID- 16610999
TI  - Biphasic lipid vesicles as a subcutaneous delivery system for protein antigens
      and CpG oligonucleotides.
AB  - One of the major drawbacks to the development of novel vaccines has been the lack
      of safe yet effective adjuvants. Biphasic lipid vesicles are formulations
      suitable for the delivery of proteins, peptides and oligo/polynucleotides. They
      constitute a new class of delivery system into which antigens and adjuvants can
      be incorporated. The purpose of these studies was to investigate the ability of
      biphasic lipid vesicles (Vaccine-Targeting Adjuvants--VTA) to induce immune
      responses to bacterial antigens and to enhance the adjuvant activity of CpG ODNs.
      Immunization of mice with bacterial antigen and CpG ODNs in saline was not as
      effective at inducing immune responses as formulation in VTA vesicles. Results
      showed that formulation of CpG ODN in VTA significantly enhanced its
      adjuvanticity.

PMID- 16611001
TI  - Delivery strategies for siRNA-mediated gene silencing.
AB  - RNA interference (RNAi) represents a promising new gene silencing technology for
      functional genomics and a potential therapeutic strategy for a variety of genetic
      diseases. RNAi involves the targeted post-transcriptional degradation of
      messenger RNA thereby inhibiting the synthesis of the desired protein. This
      effectively leads to silencing of gene expression. The effectors of this process
      are short interfering RNA (siRNA) duplexes (approximately 21-23nt) that are key
      intermediaries in the specific degradation of target mRNA following incorporation
      into the RNA-induced silencing complex (RISC) in the cytosol. However, due to the
      large molecular weight and negative charge of siRNA duplexes the effective
      cellular uptake and intracellular delivery appear to represent a major challenge
      for the widespread use of RNAi in vivo. This review summarises some of the main
      delivery strategies that have been attempted for the transfection of siRNA to
      cells in vitro and in vivo.

PMID- 16611002
TI  - Sustained and targeted delivery of an anti-HIV agent using elastic liposomal
      formulation: mechanism of action.
AB  - The present study is aimed at evaluating the transdermal route as an alternative
      to the oral route for improving the systemic bioavailability and sustaining the
      constant therapeutic plasma level of Zidovudine (AZT). Elastic liposomal
      formulations of AZT were prepared and characterized. The effect of different
      formulation variables on transdermal delivery of AZT from elastic liposomes was
      studied. To investigate the mechanism of skin permeation of elastic liposomes,
      Transmission Electron Microscopic (TEM) study was carried out. The optimized
      elastic liposomal formulation showed transdermal flux of 98.8+/-5.8 microg/cm2/hr
      across rat skin as compared to 5.72+/-0.3 microg/cm2/hr for free drug. Vesicle
      skin interaction study showed that elastic vesicles influenced the ultra
      structure of stratum corneum. Distinct regions with lamellar stacks derived from
      vesicles were observed in intercellular spaces of the stratum corneum. These
      stacks disrupted the organization of skin bilayers leading to increased skin
      permeability, whereas no changes were observed in the underlying viable epidermis
      and dermis. Improved pharmacokinetic profile was observed when AZT was entrapped
      in elastic liposomes. The AUC0-24h for elastic liposomal formulation was found to
      be (12.63+/-1.2 microg h/mL), nearly twelve fold higher than the control (0.83+/
      0.2 microg h/mL). Furthermore, the administration of elastic liposome
      encapsulated AZT resulted in substantially higher accumulation of AZT in target
      RES organs that play a key role in the pathogenesis of AIDS by providing long
      term reservoir for the virus. The results of the present study demonstrated that
      elastic liposomes increased the transdermal flux, prolonged the release, improved
      the site specificity of AZT and represented an attractive strategy for sustained
      and targeted delivery of AZT.

PMID- 16611003
TI  - Microemulsions: a potential drug delivery system.
AB  - Microemulsions are clear, transparent, thermodynamically stable dispersions of
      oil and water, stabilised by an interfacial film of surfactant frequently in
      combination with a co-surfactant. Recently, there has been a considerable
      interest for the microemulsion formulation, for the delivery of hydrophilic as
      well as lipophilic drug as drug carriers because of its improved drug
      solubilisation capacity, long shelf life, easy of preparation and improvement of
      bioavailability. In this present review, we discuss about the various advantages
      of microemulsion in pharmaceuticals, along with its composition variables,
      physicochemical characterisation etc. The potential use of microemulsion for
      therapeutic application is also discussed.

PMID- 16611004
TI  - ADME related profiling in 96 and 384 well plate format--a novel and robust HT
      assay for the determination of lipophilicity and serum albumin binding.
AB  - The failure of about half of the drug candidates is associated with poor
      pharmacokinetic properties leading to a huge loss of time and money [1]. Early
      profiling of drug like properties provides important information in order to
      screen out insoluble, poorly absorbed and toxic compounds. Today, large compound
      libraries have to be screened, and of course the total number of compounds will
      rise over the next years leading to a growing demand for fully automated assays.
      A balance between quality, speed, throughput, cost and information content can be
      accomplished by the careful selection of assays and experimental conditions. Here
      we describe a novel 384 well format assay for two important ADME related
      descriptors (lipophilicity and serum protein binding) as input parameters for a
      precise prediction of fraction absorbed, blood/organ distribution coefficients
      and permeability, in order to maximize the information about a compound at an
      early stage of discovery.

PMID- 16611005
TI  - Controlled porosity osmotic pump for the delivery of flurbiprofen.
AB  - Controlled porosity osmotic pump contains water-soluble additives in the coating
      membrane, which in contact with aqueous environment dissolves and results in
      formation of micro porous membrane. The resulting membrane is substantially
      permeable to both water and dissolved drug. The drug release from this type of
      system is independent of pH and follows zero order kinetics. In the present
      investigation, effort has been made to study release mechanism of drug having low
      water solubility by means of controlled porosity osmotic pump. The capsule
      membrane was prepared by phase inversion technique. The phase inversion was
      carried by dipping the stainless steel mould in a 15% solution of cellulose
      acetate containing varying amounts of pore-forming agent, glycerol (50% to 70%
      w/w), followed by quenching in an aqueous solution (10% w/v glycerol), which
      resulted in the formation of the asymmetric membrane. The delivery orifices so
      formed were confirmed by release of an encapsulated dye from the capsule and
      scanning electron microscope (SEM). The drug selected for this study,
      Flurbiprofen, has low water solubility and hence is unable to create osmotic
      pressure to cause drug release. To enhance the solubility and its osmotic
      pressure, this study was conducted with a solubility enhancer sodium lauryl
      sulfate (SLS). The quantity of SLS was predetermined by conducting a solubility
      study of flurbiprofen with SLS. Release rate studies revealed that less than 10%
      of drug was released from the system without SLS, while about 75% release was
      observed from systems containing SLS. The release rate increased as the
      concentration of pore forming agent increased.

PMID- 16611006
TI  - Role of ABC transporters in veterinary drug research and parasite resistance.
AB  - A considerable body of research has been carried out in order to throw light on
      the pharmacological and toxicological impact of ATP-binding cassette (ABC) drug
      efflux transporters such as P-glycoprotein and Breast Cancer Resistance Protein
      (BCRP/ABCG2/MXR). Most studies focus on their role in rendering cancer cells
      resistant to anticancer drugs. Drug transporters are expressed in many tissues
      and they are strongly involved in the oral bioavailability, and the
      hepatobiliary, direct intestinal and renal excretion of many drugs. In veterinary
      therapy, some anti parasitic drugs and/or their metabolites, such as ivermectin,
      moxidectin, albendazole sulfoxide, which are widely used, have been shown to be
      actively transported by efflux pumps. This interaction plays an important role in
      drug disposition since its inhibition has been shown to increase the drug
      bioavailability in some domestic species. Moreover, some authors have reported
      that parasite resistance to anthelmintic drugs may be mediated by parasite P
      glycoprotein efflux. In addition, the importance of milk residues for human
      nutrition has aroused increasing concern about the inadvertent transfer of drugs
      and other substances into mammary milk of domestic animals, potentially posing a
      health risk to consumers. Recently, the important role of BCRP in the secretion
      of its substrates in milk has been demonstrated.

PMID- 16611007
TI  - Review of ocular drug delivery.
AB  - Successful treatment of eye diseases requires effective concentration of drug at
      the eye for sufficient period of time. Conventional ocular drug delivery
      including eye drops, systemic administration, ophthalmic ointments, is no longer
      sufficient to combat ocular diseases. This article reviews the constraints with
      conventional ocular therapy, and explores various novel approaches, to improve
      the ocular bioavailability of drugs to the anterior chamber of the eye.

PMID- 16611008
TI  - A review of nanocarrier-based CNS delivery systems.
AB  - Drug delivery to the central nervous system (CNS) is one of the most challenging
      fields of research and development for pharmaceutical and biotechnology products.
      A number of hydrophilic therapeutic agents, such as antibiotics, anticancer
      agents, or newly developed neuropeptides do not cross the blood brain barrier
      (BBB) after systemic administration. The BBB is formed by the tight junctions at
      the brain capillary endothelial cells, which strictly control drug transfer from
      blood to brain. Drug modification, osmotic opening of cerebral capillary
      endothelium, and alternative routes for administration (e.g., intracerebral
      delivery) have been successfully used to enhance drug transport to the CNS. The
      use of nanocarriers, such as liposomes and solid polymeric or lipid nanoparticles
      may be advantageous over the current strategies. These nanocarriers can not only
      mask the BBB limiting characteristics of the therapeutic drug molecule, but may
      also protect the drug from chemical/enzymatic degradation, and additionally
      provide the opportunity for sustained release characteristics. Reduction of
      toxicity to peripheral organs can also be achieved with these nanocarriers. This
      review article discusses the various barriers for drug delivery to the CNS and
      reviews the current state of nanocarriers for enhancing drug transport into the
      CNS.

PMID- 16611010
TI  - Vicious cycles within the neuropathophysiologic mechanisms of Alzheimer's
      disease.
AB  - Rigorous scientific research has identified multiple interactive mechanisms that
      parallel and are likely causative of the development of Alzheimer's disease (AD).
      Causative mechanisms include genomics, the creation of amyloid beta (Abeta),
      factors inhibiting the Abeta removal process, the transformation of Abeta to its
      toxic forms (various forms of Abeta aggregation), and lastly the oxidative,
      inflammatory, and other effects of toxic Abeta. Fibrillar beta-amyloid peptide, a
      major component of senile plaques in AD brain, is known to induce microglial
      mediated neurotoxicity under certain conditions, but some recent studies support
      the notion that Abeta oligomers are the primary neurotoxins. Abeta-42 oligomers
      that are soluble and highly neurotoxic, referred to as Abeta-derived diffusible
      ligands (ADDLs), assemble under conditions that block fibril formation. These
      oligomers bind to dendrite surfaces in small clusters with ligand-like
      specificity and are capable of destroying hippocampal neurons at nanomolar
      concentrations. Evidence is presented that AD is triggered by these soluble,
      neurotoxic assemblies of Abeta rather than the late stage pathology landmarks of
      amyloid plaques and tangles. The premise is that AD symptoms stem from aberrant
      nerve cell signaling and synaptic failure rather than nerve cell death, which
      nevertheless follows and exacerbates the initial pathologies of AD. The defective
      clearance of amyloid leads to amyloid angiopathy that in turn perpetuates
      hypoperfusion that affects formation as well as absorption of CSF thereby
      altering clearance of amyloid and promoting vascular and parenchymal
      deposition[1]. Hypoperfusion, the defective clearance of amyloid, and resultant
      increase in amyloid deposition thus represent a vicious cycle. Chronic vascular
      hypoperfusion-induced mitochondrial failure results in oxidative damage, which
      drives caspase 3-mediated Abeta peptide secretion and enhances amyloidogenic APP
      processing. Intracellular Abeta accumulation in turn promotes a significant
      oxidative and inflammatory mechanism that generates a vicious cycle of Abeta
      generation and oxidation, each accelerating the other. Abeta activates astrocytes
      that add to the oxidative imbalance, upregulate the expression of APP via TGF
      beta, and are capable of expressing BACE1. Each of these 3 actions accelerates
      the larger cycle of cholinergic neuron destruction. As oxidative stress induces
      lesions of cholinergic nuclei producing a reduction in cholinergic
      neurotransmission, a subsequent increase in cortical APP involving PKCepsilon
      leads to accelerated amyloidogenic APP metabolism. The linkage of cholinergic
      activation and APP metabolism completes an additional feedback loop wherein the
      damage wrought by Abeta accelerates further Abeta production. A comprehensive
      vision of the neuropathophysiologic mechanisms that result in AD reveals several
      vicious cycles within a larger vicious cycle, that is to say, a number of
      interactive systems that each, once set in motion, amplify their own processes,
      thus accelerating the development of AD.

PMID- 16611011
TI  - Alzheimer's disease--an interactive perspective.
AB  - Alzheimer's disease (AD) is an age-related neurodegenerative disorder that is
      characterized by a progressive loss in memory and deterioration of the higher
      cognitive functions. The brain of an individual with AD exhibits extracellular
      senile plaques of aggregated amyloid-beta-peptide (Abeta), intracellular
      neurofibrillary tangles (NFTs) that consist of hyperphosphorylated tau protein (P
      tau) and a profound loss of basal forebrain cholinergic neurons that innervate
      the hippocampus and the neocortex. Recent data obtained via genomics, proteomics
      and molecular genetics, have gleaned new information with regard to the
      physiological and pathophysiological functions of the amyloid precursor protein
      (APP) and its cleavage product Abeta. This review glances over several aspects
      that may play a major role in the pathogenesis of AD providing an insight into
      APP's and Abeta's interplay with other cellular systems.

PMID- 16611012
TI  - Inhibition of GSK3 dependent tau phosphorylation by metals.
AB  - One of the main pathological characteristics of Alzheimer's disease is the
      presence in the brain of the patients of an aberrant structure, the paired
      helical filaments, composed of hyperphosphorylated tau. The level of tau
      phosphorylation has been correlated with the capacity for tau aggregation. Thus,
      the mechanism for tau phosphorylation could be important to clarify those
      pathological features in Alzheimer's disease. Tau protein could be modified by
      different kinases, being GSK3 the one that could modify more sites of that
      protein. GSK3 activity could be modulate by the presence of metals like magnesium
      that can be required for the proper function of the kinase, whereas, metals like
      manganesum or lithium inhibit the activity of the kinase. Many works have been
      done to study the inhibition of GSK3 by lithium, a specific inhibitor of that
      kinase. More recently, it has been indicated that sodium tungstate could also
      inhibit GSK3 through a different mechanism. In this review, we discuss the effect
      of these two metals, lithium and tungstate, on GSK3 (or tau I kinase) activity.

PMID- 16611013
TI  - Treating Alzheimer's disease by inactivating bioactive amyloid beta peptide.
AB  - Treating Alzheimer's disease (AD) is one of today's biggest unmet medical needs.
      The drugs currently available transiently relieve some symptoms but have no
      significant effects on the progression of the disease. Progress in the past
      decade suggests that the amyloidogenesis of the inactive monomeric amyloid beta
      peptide (Abeta) into a subset of toxic Abeta polymers is responsible for
      neurodegeneration in AD. Not all forms of Abeta aggregates are damaging, for
      there are patients whose brains accumulated large amounts of Abeta in the form of
      plaques, but they had no obvious neurodegeneration and symptoms of dementia.
      Since Abeta can polymerize into many types of polymers or aggregates, the form of
      Abeta that induces neurodegeneration in AD, defined here as bioactive Abeta, is
      not clear. Preventing the formation of bioactive Abeta or inactivating previously
      formed bioactive Abeta is a promising approach for treating AD. This review
      describes our efforts to develop a cell-based assay for detecting bioactive
      Abeta, to verify the concept of bioactive Abeta in an animal model of AD and in
      post mortem brain tissue from AD patients, and to use this assay to screen for
      drugs that can inactivate bioactive Abeta. These studies show the proof in
      principle that inactivating bioactive Abeta is a promising approach to treat AD.
      Several promising compounds that can inactivate bioactive Abeta species are also
      described.

PMID- 16611014
TI  - Pharmacological manipulation of the vasoconstrictive effects of amyloid-beta
      peptides by donepezil and rivastigmine.
AB  - The amyloid-beta (Abeta) peptide has been linked to the pathology of Alzheimer's
      disease (AD). There is now evidence to support a vasoconstrictive effect of Abeta
      protein that could be detected in peripheral skin microvasculature. In this study
      we investigated the ability of acetylcholinesterase (AChE) inhibitors, Donepezil
      and Rivastigmine, to modulate the vasoconstrictor activity of Abeta25-35 and
      Abeta1-40. The ability of these drugs to improve endothelial mediated vascular
      responses to acetylcholine and bradykinin subsequent to perfusion of Abeta
      peptides was also investigated. The vascular responses to Abeta peptides,
      acetylcholine, bradykinin and sodium nitroprusside and their modulation by
      acetylcholinesterase inhibitors were examined in the base of a vacuum induced
      blister raised on the rat hind footpad using laser Doppler flowmetry. Abeta25-35
      (1 microM) and Abeta1-40 (0.1 microM) induced a vasoconstrictor effect and
      significantly reduced the vasodilator response to acetylcholine (100 microM) and
      bradykinin (1 microM). Donepezil (100 microM) and Rivastigmine (100 microM) both
      reduced the vasoconstrictor effect of Abeta peptides, and significantly restored
      the endothelial vascular response to acetylcholine. Similarly, Donepezil
      significantly restored the endothelial vascular response to bradykinin. The
      results also showed that the actions of acetylcholinesterase inhibitors are
      independent of a direct action on smooth muscle cell reactivity or on endothelial
      cell function in the absence of Abeta. The current study provides the first
      evidence in vivo to suggest that acetylcholinesterase inhibitors modulate the
      vasoconstrictive effects of Abeta peptides at the level of skin microvasculature.
      We raise the notion that Donepezil and Rivastigmine mediate these vascular
      modulatory effects via an action on Abeta-mediated vasoconstrictor mechanisms
      rather than an independent action on endothelial or smooth muscle cell mediated
      responses.

PMID- 16611015
TI  - Cholinesterase inhibitors slow decline in executive functions, rather than
      memory, in Alzheimer's disease: a 1-year observational study in the Sunnybrook
      dementia cohort.
AB  - To determine if there are differential treatment effects of second-generation
      cholinesterase inhibitors over one year, 130 patients (untreated=65, treated=65)
      meeting NINCDS-ADRDA criteria for mild or moderate probable AD underwent
      standardized cognitive testing at baseline and 12 months later at a university
      memory clinic. Patients were followed either prior to or after the availability
      of treatment and were matched on education and baseline Mini Mental State
      Examination (MMSE). A detailed medical history evaluation was conducted. In this
      well matched longitudinal observational cohort study, there were no differences
      in the prevalence of comorbid illnesses, concomitant medication use or vascular
      risk factors except for a greater number of treated patients with a previous
      history of smoking. Separate repeated measures MANCOVAs on the MMSE, Mattis
      Dementia Rating Scale (DRS), and its 5 subscores (attention,
      initiation/perseveration, conceptualization, construction and memory) (Bonferroni
      corrected), after covarying for the effects of smoking, and SSRI use, showed less
      decline over one year in the treated group in overall cognition and in all
      subscores of the DRS except for memory (effect sizes 0.5-0.7). Less decline was
      also seen in the treated group in function and in instrumental and basic
      activities of daily living as measured with the Disability Assessment for
      Dementia Scale (DAD) (effect sizes 0.4-0.8). Executive, language and visuospatial
      functions, rather than memory, appeared to be more amenable to stabilization over
      one year by cholinesterase inhibitors in AD.

PMID- 16611016
TI  - Studies on the effect of the apolipoprotein E genotype on the lipid profile in
      Alzheimer's disease.
AB  - OBJECTIVE: To determine whether Apolipoprotein E4 (Apo E4) gene status or ApoE
      gene dose affect the lipid profile in AD. BACKGROUND: Links between
      hypercholesterolemia and AD development continue to grow. Presently, limited
      information exists about the influence of the Apo E genotype on the lipid profile
      characteristics in AD. METHODS: We examined the lipid profiles (total cholesterol
      (TC), high-density lipoprotein (HDL), lower-density lipoprotein (LDL), TC/HDL
      ratio, and triglyceride (TG) levels) of 142 subjects with probable or possible AD
      (mean age 76.5 +/- 8.9 years), not on lipid lowering therapy by Apo E genotype.
      Assessment was done by gene status and gene dose. RESULTS: ApoE4 gene status did
      not reveal any significant differences in the lipid profile except for LDL.
      However, significant differences were observed by ApoE gene dose. CONCLUSION:
      ApoE gene status has minimal influence on the lipid panel or mean age in AD. Apo
      E gene dose does influence the lipid panel with Apo E 2/2, and 2/3 having
      significantly better lipid panels and older age of onset.

PMID- 16611017
TI  - Predictors of conversion to dementia of probable Alzheimer type in patients with
      mild cognitive impairment.
AB  - BACKGROUND: Mild Cognitive Impairment is a common condition defined as
      transitional state between normality and dementia of Alzheimer type. Clinically
      is characterized by subjective and objective memory loss beyond the expected for
      age and educational level, although a broad range of cognitive inefficiencies may
      appear, with preservation of daily living activities. Approximately half the
      patients convert to dementia within 3 years. Since no all patients convert to
      dementia it is essential to find reliable predictors so as to start the
      appropriate treatment as soon as possible. METHOD: Extensive Medline-based search
      for articles dealing with predictors of conversion to dementia in Mild Cognitive
      Impairment (MCI). RESULTS: There is a substantial body of literature dealing with
      predictors of dementia in patients with MCI. These predictors range from a simple
      delayed recall task on Mini-Mental to sophisticated radiological techniques and
      CSF biomarkers. Comprehensive neuropsychological tests rarely surpass 70%
      sensitivity and specificity. The presence of the APOE epsilon 4 allele has been
      associated with increased risk of conversion but the sensitivity is quite low.
      CSF biochemical markers are being developed with encouraging results. beta
      amyloid 42 protein is usually lower in converters than in people with stable
      cognitive status and tau protein is higher. The sensitivity is substantial but
      specificity is so far low. An epitope of tau protein (P231) looks more specific
      of Alzheimer's disease and therefore a promising biomarker. In the blood, high
      beta-amyloid protein levels indicate risk of conversion but only a few studies
      have been published. Hippocampal or entorhinal atrophy on MRI is one of the most
      used radiological markers of conversion but quantification of atrophy is not
      simple as it is subject to artifacts and anatomic variations. Proton Magnetic
      Resonance Spectroscopy (MRS) and Positron Emission Tomography (PET) are emerging
      as the most promising predictive tools. The highest degree of accuracy (>90%) has
      been achieved by means of PET plus either memory performance or APOE4 genotype.
      However, the samples of the published studies are mostly small, and these
      instruments are not widely available. CONCLUSIONS: There is no enough evidence to
      recommend specific techniques for predictions. Until an accurate marker is
      developed, a combined use of cognitive tests, APOE genotype, and a
      neuroradiological technique is probably the best option for prediction purposes
      depending on availability and experience.

PMID- 16611018
TI  - Reactive intermediates and the pathogenesis of adverse drug reactions: the
      toxicology perspective.
AB  - Severe adverse drug responses are infrequent but occasionally serious events that
      are not readily predictable at the preclinical development level using only non
      human or in vitro models. A common characteristic of the more serious toxicities
      is generation of short-lived and highly reactive electrophilic species in some
      individuals. The objective here is to review the literature for toxicological
      mechanisms that underlie known adverse drug reactions and then categorize the
      biological consequences of reactive chemical intermediates and radicals in terms
      of human risk factors and known metabolic variables. Xenobiotics described as
      being associated with rare but potentially serious adverse events affecting
      liver, skin, or causing blood dyscrasias tend to have three of four essential
      characteristics, (1) they are capable of forming short-lived reactive
      intermediates (RI) or free radicals in target tissues under ideal conditions that
      are distinct from primary metabolic products, (2) these RI escape/overwhelm the
      detoxification mechanisms associated with the site of origin or form toxic
      conjugates, (3) the unconjugated RI must either selectively damage critical
      proteins or other key macromolecules or (4) the RI acts as a hapten and
      stimulates an immunological (hypersensitivity) response or overcomes tolerance.
      Some risk factors may increase the probability of susceptibility, but this
      remains an active area of research. Because of the complexity of the pathogenesis
      of some injuries and the role of individual factors, no highly predictive in
      vitro screening methods are available; however, several methods are evolving that
      may be used to reveal mechanisms of action when a serious adverse effect is
      encountered.

PMID- 16611019
TI  - A literature review of enzyme kinetic parameters for CYP3A4-mediated metabolic
      reactions of 113 drugs in human liver microsomes: structure-kinetics relationship
      assessment.
AB  - Cytochrome P450 (CYP) enzymes represent a superfamily of hemoproteins that are
      involved in the metabolism of a wide variety of endogenous and exogenous
      compounds. For a given CYP enzyme, kinetic properties of a substrate are usually
      related to substrate lipophilicity (log P or log D(7.4)). In this review, enzyme
      kinetic parameters (K(m), V(max), and V(max)/K(m)) of 215 CYP3A4-mediated
      metabolic reactions of 113 drugs in human liver microsomes were obtained from the
      literature, and lipophilicity values of the 113 drugs were calculated using the
      ACD/Labs 8.0 program. A low degree of K(m)- or (V(max)/K(m))-lipophilicity
      correlation, but no V(max)-lipophilicity correlation, is exhibited for the CYP3A4
      mediated reactions. Overall, K(m) decreases, but V(max)/K(m) increases, with
      increasing substrate lipophilicity, and V(max) appears to be independent of
      substrate lipophilicity. In other words, a low K(m) generally confers a high
      V(max)/K(m) ratio for a substrate. The degree of lipophilicity-kinetics
      correlations is related to both reaction types (or reaction mechanisms) and
      regiochemical positions (or physicochemical properties) of the reaction groups of
      the substrates. Among the categorized CYP3A4-mediated reactions, the best
      lipophilicity-kinetics correlation is achieved for carbon hydroxylation, followed
      by N-dealkylation. No or little lipophilicity-kinetics correlations are seen for
      N, S-oxidation and other reactions. Within the hydroxylation group, aliphatic
      hydroxylation shows the best lipophilicity-kinetics correlation while
      hydroxylation on a carbon atom adjacent to an aromatic ring does not show any
      lipophilicity-kinetics correlation. The detailed structural and kinetic data sets
      of the human liver microsomal CYP3A4-mediated reactions represent a specialized
      database useful for researchers working in the area of structure-metabolism
      relationship modeling and analysis.

PMID- 16611020
TI  - The impact of in vitro binding on in vitro-in vivo extrapolations, projections of
      metabolic clearance and clinical drug-drug interactions.
AB  - This review provides a vista of the current opportunities and remaining
      challenges in the area of in vitro-in vivo extrapolation, with particular
      emphasis on drug binding terms in predictive models, which has been the source of
      much controversy. Although the importance of fu(inc) (fraction unbound in in
      vitro incubations) has been acknowledged for decades, it is not always applied in
      practice. This is somewhat disappointing, since although it may be onerous to
      measure this term for large numbers of compounds, algorithms to estimate the term
      from logD(7.4) or logP have been detailed in the literature. These are
      sufficiently robust to negate routine measurement in early drug discovery.
      Several groups have recently established convincing relationships between unbound
      in vivo and in vitro metabolic intrinsic clearance (CL(int)). In the authors'
      laboratory, correlations of this type have been constructed for rat, dog and Man.
      The use and interpretation of these models within a drug discovery setting is
      discussed. The quantitative prediction of drug-drug interactions from in vitro
      cytochrome P450 (CYP) inhibition data remains a challenge. Although extensive
      literature databases are at last emerging, apparent ad hoc use of terms for in
      vivo inhibitor concentrations and only occasional consideration of fu(inc) may
      only have confused matters. The effect of accounting for drug binding on the
      accuracy of predictions is reviewed. Other themes including the impact of fu(inc)
      on relative activity factors (RAFs) and how in vitro data quality and inter
      laboratory differences can confound quantitative human pharmacokinetic
      predictions are also developed.

PMID- 16611021
TI  - Evaluation of microsomal incubation conditions on CYP3A4-mediated metabolism of
      cyclosporine A by a statistical experimental design.
AB  - The effect of changes in microsomal incubation conditions (NADPH, Mg(2+), Cl(-),
      NADPH-regenerating system and pH) on the formation of the CYP3A4 metabolites AM1
      and AM9 from CsA were studied by application of a fractional factorial design.
      Metabolism was studied in microsomes of transfected human liver epithelial (THLE)
      cells specifically expressing CYP3A4. Within the conditions tested, a 3-4-fold
      difference in formation of CsA metabolites was observed. Formation of both AM1
      and AM9 was favoured by a low Mg(2+) concentration (0.5 mM) and no addition of
      Cl(-) to the incubation matrix. However, while a high NADPH concentration (1.75
      mM) was the single most important factor for the formation of AM1, changes in
      NADPH concentration between 0.25 and 1.75 mM had no influence on AM9 formation.
      Formation of the two metabolites also differed in their influence by pH changes,
      as a change in pH from 7.2 to 7.5 significantly increased the formation of AM9,
      while formation of AM1 was unaffected by this change. The present study showed
      that relatively small changes in the incubation matrix had a significant
      influence on the microsomal CYP3A4-mediated metabolism of CsA. Systematic studies
      on microsomal incubation conditions could be a key to improve metabolic in vitro
      in vivo extrapolations in drug development.

PMID- 16611022
TI  - Candidate susceptibility genes in Alzheimer's disease are at high risk for being
      forgotten-- they don't give peace of mind...
AB  - Alzheimer's disease (AD) is a genetically complex and heterogenous disorder. In a
      small proportion of cases, mutations in three determinative (causal) genes are
      responsible for autosomal dominant early-onset forms of AD. The majority of
      cases, however, is sporadic, late-onset AD with unknown etiology. The pathology
      and clinical manifestations of these forms are influenced by multiple genetic and
      environmental risk factors. Over the past decades, a number of candidate genes
      have been identified as disease modifiers with conflicting results. This study
      reviews susceptibility genes that are associated with increased risk of
      developing AD.

PMID- 16611023
TI  - Prediction of maximum exposure in poor metabolizers following inhibition of
      nonpolymorphic pathways.
AB  - Marked increases in exposure of some substrates have been noted in poor
      metabolizers given inhibitors of nonpolymorphic enzymes. Among the small number
      of clinical trials conducted to investigate this problem, a wide variation in the
      degree of maximum exposure ratios (area under the curve in poor metabolizers in
      the presence of inhibitor/area under the curve in extensive metabolizers) among
      the different substrates has been reported, with some trials reporting profound
      increases (> tenfold), and others demonstrating less remarkable changes (<
      twofold). The conduct of such trials raises safety concerns for the trial
      participants, in addition to other ethical and logistic concerns; therefore, the
      possibility was investigated that maximum exposure (area under the curve in poor
      metabolizers in the presence of an inhibitor) could be predicted, and that
      substrates susceptible to large increases in exposure could be identified.
      Existing clinical trials were identified by data mining the literature. A
      theoretical approach was developed to predict maximum exposure in poor
      metabolizers from studies in extensive metabolizers treated with an inhibitor of
      the nonpolymorphic pathway. Maximum exposure was predicted in eleven instances
      and the mean percentage difference between predicted and observed was 11.9%.
      Substrates with a fraction of substrate dose metabolized by the polymorphic
      enzyme (fm(POLY)) higher than 75% are at greater risk of exhibiting maximum
      exposure ratios of more than tenfold.

PMID- 16611024
TI  - Involvement of cytoskeleton in AhR-dependent CYP1A1 expression.
AB  - Cytochrome P450 (CYP) 1A1 attracts attention mainly because of its role in
      production of carcinogenic reactive metabolites from polycyclic aromatic
      hydrocarbons such as benzo[a]pyrene, but recent developments indicate its
      apparent role in cell cycle progression. Expression of the enzyme is subject to
      regulation by aryl hydrocarbon receptor (AhR). It has been shown that induction
      of CYP 1A1 in HepG2 cells and primary rat hepatocytes by tetrachloro-p
      dibenzodioxin (TCDD) is diminished by colchicine and nocodazole. Both compounds
      decrease CYP1A1 mRNA, protein, and activity levels in HepG2 cells and mRNA level
      in primary rat hepatocytes. Neither compound significantly affected [(3)H]-TCDD
      binding to AhR, thus their effect on AhR transcriptional activity proceeds via
      indirect means. For colchicine and nocodazole are well-known microtubule
      interfering agents, we also assessed their effect on microtubule integrity in
      both cell types under investigation. Both compounds disrupt cytoskeleton
      integrity with differential potency depending on cell type. The observed
      suppression of AhR transcriptional activity by colchicine and nocodazole can be
      associated with G2/M cell cycle arrest in HepG2 cells, as demonstrated by Myt1
      protein hyperphosphorylation and FACS analysis. However, in primary rat
      hepatocytes, cytoskeleton disruption is independent of cell cycle while
      displaying the same influence on AhR-dependent gene transcription. In our view,
      this is evidence in favor of modulatory role of cytoskeleton in AhR-dependent
      expression.

PMID- 16611025
TI  - A critical evaluation of the experimental design of studies of mechanism based
      enzyme inhibition, with implications for in vitro-in vivo extrapolation.
AB  - The published literature on mechanism based inhibition (MBI) of CYPs was
      evaluated with respect to experimental design, methodology and data analysis.
      Significant variation was apparent in the dilution factor, ratio of preincubation
      to incubation times and probe substrate concentrations used, and there were some
      anomalies in the estimation of associated kinetic parameters (k(inact), K(I), r).
      The impact of the application of inaccurate values of k(inact) and K(I) when
      extrapolating to the extent of inhibition in vivo is likely to be greatest for
      those compounds of intermediate inhibitory potency, but this also depends on the
      fraction of the net clearance of substrate subject to MBI and the pre-systemic
      and systemic exposure to the inhibitor. For potent inhibitors, the experimental
      procedure is unlikely to have a material influence on the maximum inhibition.
      Nevertheless, the bias in the values of the kinetic parameters may influence the
      time for recovery of enzyme activity following re-synthesis of the enzyme.
      Careful attention to the design of in vitro experiments to obtain accurate
      kinetic parameters is necessary for a reliable prediction of different aspects of
      the in vivo consequences of MBI. The review calls for experimental studies to
      quantify the impact of study design in studies of MBI, with a view to better
      harmonisation of protocols.

PMID- 16611027
TI  - Investigating the molecular basis of drug action and response: chemocentric
      genomics and proteomics.
AB  - The genomics and proteomics sciences have fundamentally changed the ways in which
      drug targets are being identified, characterized and validated. Here we review
      how genomics and proteomics research is improving our understanding of genetic
      determinants of drug susceptibility and response and, conversely, how organic
      small molecules mediate their pharmacological effects by modulating genome and
      proteome activities. We also examine the effect this improved understanding has
      on the drug discovery and development process.

PMID- 16611028
TI  - Discovery of new small molecules and targets towards angiogenesis via chemical
      genomics approach.
AB  - Chemical genetics/genomics is an inter- and multi-disciplinary research engine,
      which utilizes small molecules to explore the function of genes and accelerate
      the drug discovery. Bioactive small molecules that are permeable to cellular
      membrane and bind to its cognate target protein can exert the phenotype changes
      of the cells or organisms. Functional target proteins of these small molecules
      have been successfully identified by affinity, genetics and genomics based target
      identification. The specific molecular recognition of small molecule with target
      protein has facilitated to decipher the mode of actions of small molecules and
      developed better drug based on their structure activity relationship. Based on
      this idea, we have applied chemical genomics to angiogenesis, a new blood vessel
      formation, resulting in the identification of new small molecules as well as
      targets. In this review, our application of chemical genomics towards a cellular
      phenotype, angiogenesis, will be demonstrated.

PMID- 16611029
TI  - Molecular pharmacology and pharmacogenomics of artemisinin and its derivatives in
      cancer cells.
AB  - Secondary metabolites from plants can serve as defense against herbivores,
      microbes, viruses or competing plants. Many compounds from medicinal plants have
      pharmacological activities and thus may be a source for novel anti-tumor agents.
      We have analyzed natural products from traditional Chinese medicine during the
      past decade and focused our interest on the compound artemisinin from Artemisia
      annua L. (qinghao, sweet wormwood) and its derivatives. In addition to their anti
      malarial properties, artemisinins are cytotoxic for cancer cells. The present
      review focuses on the mechanisms of action of artemisinins in cancer cells
      relating to: 1. anti-proliferative and anti-angiogenic effects, 2. induction of
      apoptosis, 3. oxidative stress, 4. oncogenes and tumor suppressor genes, and 5.
      multidrug resistance. Data on putative target molecules of artemisinins are
      presented and discussed, e.g. the translationally controlled tumor protein
      (TCTP). Emphasis is given to pharmacogenomic approaches to analyze the
      pleiotropic nature of mechanisms of artemisinins in cancer cells.

PMID- 16611030
TI  - Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer.
AB  - Resveratrol (3,4',5 tri-hydroxystilbene) is a phytoalexin produced in hudge
      amount in grapevine skin in response to infection by Bothrytis cinerea. This
      production of resveratrol blocks the proliferation of the pathogen, thereby
      acting as a natural antibiotic. Numerous studies have reported interesting
      properties of trans-resveratrol as a preventive agent against important
      pathologies i.e. vascular diseases, cancers, viral infection or neurodegenerative
      processes. Moreover, several epidemiological studies have revealed that
      resveratrol is probably one of the main microcomponents of wine responsible for
      its health benefits such as prevention of vaso-coronary diseases and cancer.
      Resveratrol acts on the process of carcinogenesis by affecting the three phases:
      tumor initiation, promotion and progression phases and suppresses the final steps
      of carcinogenesis, i.e. angiogenesis and metastasis. It is also able to activate
      apoptosis, to arrest the cell cycle or to inhibit kinase pathways. Interestingly,
      resveratrol does not present any cytotoxicity in animal models. Moreover,
      concentrations of resveratrol in blood seem to be sufficient for anti-invasive
      activity. The enterohepatic recirculation may contribute to a delayed elimination
      of the drug from the body and bring about a prolonged effect. By its binding to
      plasmatic proteins, resveratrol also exhibits a prolonged effect. Interestingly,
      low doses of resveratrol can sensitize to low doses of cytotoxic drugs and so
      provide an innovative strategy to enhance the efficacy of anticancer therapy in
      various human cancers. By these properties, resveratrol appears to be a good
      candidate in chemopreventive or chemotherapeutic strategies and is believed to be
      a novel weapon for new therapeutic strategies.

PMID- 16611031
TI  - Histone deacetylases as targets for dietary cancer preventive agents: lessons
      learned with butyrate, diallyl disulfide, and sulforaphane.
AB  - Cancer is a multi-factorial process involving genetic and epigenetic events which
      result in neoplastic transformation. Reversal of aberrant epigenetic events,
      including those that modulate the transcriptional activity of genes associated
      with various signaling pathways, holds the prospect of influencing multiple
      stages of tumorigenesis. Perturbation of normal histone acetylation status can
      result in undesirable phenotypic changes, including developmental disorders and
      cancer. Indeed, aberrant histone acetylation may be an etiological factor in
      several, if not all, types of cancer. In general, histone acetylation leads to
      chromatin remodeling and a de-repression of transcription. Histone deacetylase
      (HDAC) inhibitors may be useful for cancer prevention and therapy by virtue of
      their ability to 'reactivate' the expression of epigenetically silenced genes,
      including those involved in differentiation, cell cycle regulation, apoptosis,
      angiogenesis, invasion, and metastasis. Several natural and synthetic HDAC
      inhibitors have been shown to affect the growth and survival of tumor cells in
      vitro and in vivo. Interestingly, three dietary chemopreventive agents, butyrate,
      diallyl disulfide, and sulforaphane, also have HDAC inhibitory activity. This
      review discusses the role of aberrant histone acetylation in tumorigenesis and
      describes the potential for cancer chemoprevention and therapy with a particular
      emphasis on dietary HDAC inhibitors.

PMID- 16611032
TI  - Production of paclitaxel and the related taxanes by cell suspension cultures of
      Taxus species.
AB  - Medicinal plants are the most promising source for the development of drugs, and
      many types of active ingredients from the plant resources have been studied in
      order to clarify the relationship between the chemical structure and the
      activity. However, it is not easy to develop drugs from those active compounds,
      and in many cases, the supply of active compounds can have some problems: 1)
      limited quantity of active compounds in plant; 2) low plant growth rate; 3) the
      limited localization of active ingredients in the specific organs; and 4) from
      the perspective of the conservation of natural resources. Therefore, the stable
      supply of the compounds commercially is very difficult and contains risk hedge.
      Plant cell culture is an attractive technology to solve these problems by
      securing the stable supply of the active compounds without damage to the natural
      plant resources. Recently, an efficient production process of anticancer drug
      paclitaxel by Taxus cell suspension cultures was constructed. The established
      Taxus cell lines produced paclitaxel and related taxanes by specific external
      stimuli, such as methyl jasmonate. The time-course analysis revealed that there
      are two regulatory steps existing in the paclitaxel biosynthesis: the taxane-ring
      formation step that is up-regulated by MeJA, and the acylation step at the C-13
      position. By applying the data from the two-stage culture and the high-density
      culture, a large-scale culture process was developed with a stable paclitaxel
      production in the range of 140-295 mg L(-1), reaching 295 mg L(-1) at maximum.

PMID- 16611034
TI  - Biofilms and their role in the resistance of pathogenic Candida to antifungal
      agents.
AB  - Fungal pathogens of the genus Candida form biofilms on catheters and prosthetic
      devices. These three-dimensional structures composed of yeast and hyphal cells
      embedded in an extracellular matrix constitute an important pitfall in the
      management of disseminated Candida infections because of their intrinsic
      resistance to almost all antifungals in clinical use. Candida biofilms are
      especially resistant to azoles and amphotericin B but remain sensitive to the
      newly introduced echinocandins that target cell wall beta-glucan biosynthesis.
      Antifungal resistance of biofilms results most probably from the conjunction of
      several mechanisms that act in a time-dependent manner. While drug efflux is
      likely to contribute to resistance during the early phases of biofilm formation,
      changes in the sterol composition of membranes might explain the resistance of
      mature biofilms. The original physiology of mature Candida biofilms is mirrored
      by specific gene expression patterns that may pinpoint genes important for the
      acquisition of pleiotropic antifungal resistance.

PMID- 16611035
TI  - Fungal ATP-binding cassette (ABC) transporters in drug resistance &
      detoxification.
AB  - Pleiotropic drug resistance (PDR) is a well-described phenomenon occurring in
      fungi. PDR shares several similarities with processes in bacteria and higher
      eukaryotes. In mammalian cells, multidrug resistance (MDR) develops from an
      initial single drug resistance, eventually leading to a broad cross-resistance to
      many structurally and functionally unrelated compounds. Notably, a number of
      membrane-embedded energy-consuming ATP-binding cassette (ABC) transporters have
      been implicated in the development of PDR/MDR phenotypes. The yeast Saccharomyces
      cerevisiae genome harbors some 30 genes encoding ABC proteins, several of which
      mediate PDR. Therefore, yeast served as an important model organism to study the
      functions of evolutionary conserved ABC genes, including those mediating clinical
      antifungal resistance in fungal pathogens. Moreover, yeast cells lacking
      endogenous ABC pumps are hypersensitive to many antifungal drugs, making them
      suitable for functional studies and cloning of ABC transporters from fungal
      pathogens such as Candida albicans. This review discusses drug resistance
      phenomena mediated by ABC transporters in the model system S. cerevisiae and
      certain fungal pathogens.

PMID- 16611036
TI  - Host-pathogen interactions and the pathological consequences of acute systemic
      Candida albicans infections in mice.
AB  - Candida albicans is a commensal organism that lives as benign member of the
      microflora of healthy individuals. In response to changes in the host immune
      status or microflora, C. albicans ceases to be a commensal organism and infects a
      variety of host tissues. The capacity to shift from a commensal to pathogenic
      state requires a coordinated metabolic response that triggers discrete
      developmental programs and that induce the expression of specific virulence
      traits. Several virulence traits have been described in C. albicans including
      adhesion, morphological and phenotypic switching, and the production of secreted
      hydrolytic enzymes. These attributes contribute to host tissue recognition,
      tissue invasion and colonization, as well as evasion of the host immune response.
      Recent experimental progress has illuminated some of the cellular processes that
      enable Candida cells to sense and respond to changes in the host environment.
      Similarly, cells of the host innate immune system are able to recognize invading
      C. albicans cells and induce a complex immune response that ultimately determines
      the clinical outcome of the infection. In this review we describe the current
      understanding of the events taking place during systemic infections of C.
      albicans. The interplay between defined pathogen and host specific responses are
      discussed. Additionally, we provide experimental data on the pathological
      consequences resulting from acute systemic infections of C. albicans in mice.

PMID- 16611037
TI  - Epidemiology of Candida albicans infections and role of non-Candida-albicans
      yeasts.
AB  - Infections of the skin and the mucous membranes due to Candida species may occur
      either in immuncompromised or in non-immuncompromised patients. This is in
      contrast to systemic candidiasis (e.g. candidemia) which is only seen in severely
      immunocompromised patients. Bloodstream infections caused by Candida species are
      increasingly recognized in critical ill adult and pediatric individuals, with
      significant associated morbidity and mortality. Candida albicans is the single
      most common fungal species causing nosocomial infections. However, non-Candida
      albicans spp., including fluconazole-less-susceptible Candida glabrata, have
      become more common pathogens. In some patient populations such as hematological
      (neutropenic) patients Non-C. albicans species are detected much more frequently
      as compared to non-neutropenic patients in the intensive care. Non-C. albicans
      species are more likely to occur in patients, who receive or have received
      antifungal therapy with azoles (e.g. fluconazole). In this review the current
      epidemiological trends in mucosal and invasive candidiasis are discussed with
      regard to the role of non-Candida albicans species as the causative agent in
      immunocompromised patients.

PMID- 16611038
TI  - Getting in touch with Candida albicans: the cell wall of a fungal pathogen.
AB  - The cell wall of fungi is a highly complex structure consisting of a network of
      polysaccharides in which a plethora of different proteins are embedded. It is one
      of the major organelles of the cell surrounding it like an armor which protects
      from environmental stresses like osmotic pressure and defines the shape and
      physical strength of the fungal cell. It is crucial for colonization and
      infection since it defines the interface between host and pathogen. No similar
      structure is present in the host, therefore it defines a prime target for drug
      development. In this context, it has been shown that cell surface proteins are
      required for adhesion to host cells. The fact, that both pathogenic fungi, like
      Candida albicans as well as non-pathogenic fungi, like Saccharomyces cerevisiae,
      in general, have a very similar polysaccharide structure but differ significantly
      in their protein composition which underscores the importance of cell wall
      proteins for pathogenesis. However, cell wall proteomics of fungi is a highly
      challenging task due to the complex biochemistry of these proteins. The extensive
      post-translational modifications and covalent attachment to the polysaccharide
      backbone of a large proportion of cell wall proteins makes it a demanding task to
      isolate and identify them. In this article, we describe the recent approaches
      that have been developed to describe cell wall dynamics and to isolate and
      identify cell wall proteins in the pathogenic yeast C. albicans.

PMID- 16611039
TI  - Laboratory diagnosis and therapy of invasive fungal infections.
AB  - Diagnosing fungal infections remains a problem, particularly in the
      immunocompromised patient. Symptoms are mostly non-specific and colonization is
      difficult to distinguish from invasive disease. Existing diagnostic tools often
      lack sensitivity. Thus, the combination of various diagnostic tools is mandatory
      to allow earlier diagnosis of systemic fungal infections. Microscopy, culture
      based methods, antigen detection, and PCR may help to facilitate and accelerate
      the diagnosis. Galactomannan and glucan are two promising antigens that may be
      useful for early detection of the infection, but also for therapeutic monitoring.
      Sensitive and specific PCR assays to detect fungal DNA are an important part of
      the diagnostic approach. But extensive validation and standardization is strongly
      needed, before PCR assays can be used in a routine laboratory. The tremendous
      increase in invasive fungal infections has led to an increased interest in new
      antifungal agents and the field of antifungal chemotherapy evolved even more
      rapidly than diagnostic assays. The development of less toxic formulations of
      amphotericin B, the introduction of improved azoles and the availability of the
      echinocandins are opening new opportunities for the treatment of fungal
      infections. However, continuing efforts in the laboratory and well-designed
      clinical trials are still needed.

PMID- 16611040
TI  - Gene therapy for cystic fibrosis airway disease- is clinical success imminent?
AB  - Cystic fibrosis (CF) was one of the first inherited disorders for which gene
      therapy was seriously considered as a realistic option for treatment, and as
      such, it has long provided a paradigm for gene therapy of inherited diseases.
      However, despite the cloning of the cystic fibrosis transmembrane conductance
      regulator gene in 1989, over 15 years later a practical gene therapy for CF has
      not eventuated. There are a number of reasons for this, and analysis of the
      specific issues that have delayed the successful development of gene therapy for
      CF also provides general insights into the practical complexities involved in the
      development of gene therapy for inherited disorders. The issues which have
      prevented the application of gene therapy for CF to date include the lack of
      suitable gene delivery technologies, the complexities of the interactions between
      the host and vector, the biology of the lung airways, and the nature of the
      pathology found in individuals with CF. We will discuss the history of CF gene
      therapy with specific reference to these and other issues that pre-occupy the
      field at present: namely, the question of what vectors appear to be suitable for
      airway gene delivery in CF, what cells must be targeted, how airway epithelium
      defences can be overcome or eluded to allow efficient gene delivery, how to
      ensure safe and long-term transgene expression and the need to identify relevant
      surrogate success measures that can be used to assess the outcome of gene therapy
      in CF patients.

PMID- 16611041
TI  - Immuno-isolation in cancer gene therapy.
AB  - The implantation of genetically-modified non-autologous cells in immuno-protected
      microcapsules is an alternative to ex vivo gene therapy. Such cells delivering a
      recombinant therapeutic product are isolated from the host's immune system by
      being encapsulated within permselective microcapsules. This approach has been
      successful in pre-clinical animal studies involving delivery of hormone or
      enzymes to treat dwarfism, lysosomal storage disease, or hemophilia B. Recently,
      this platform technology has shown promise in the treatment for more complex
      diseases such as cancer. One of the earliest strategy was to augment the
      chemotherapeutic effect of a prodrug by implanting encapsulated cells that can
      metabolise prodrugs into cytotoxic products in close proximity to the cancer
      cells. More recent approaches include enhancing tumor cell death through
      immunotherapy, or suppressing tumor cell proliferation through anti-angiogenesis.
      These can be achieved by delivering single molecules of cytokines or angiostatin,
      respectively, by implanting microencapsulated cells engineered to secrete these
      recombinant products. Recent refinements of these approaches include genetic
      fusion of cytokines or angiostatin to additional functional groups with tumor
      targeting or tumor cell killing properties, thus enhancing the potency of the
      recombinant products. Furthermore, a COMBO strategy of implanting
      microencapsulated cells to deliver multiple products targeted to diverse pathways
      in tumor suppression also showed much promise. This review will summarise the
      application of microencapsulation of genetically-modified cells to cancer
      treatment in animal models, the efficacy of such approaches, and how these
      studies have led to better understanding of the biology of cancer treatment. The
      flexibility of this modular system involving molecular engineering, cellular
      genetic modification, and polymer chemistry provides potentially a huge range of
      application modalities, and a tremendous multi-disciplinary challenge for the
      future.

PMID- 16611042
TI  - Basic and clinical aspects of gene therapy for retinopathy induced by diabetes.
AB  - Diabetes mellitus invariably induces retinopathy which causes a loss of vision
      that is the major cause of blindness in people of working age across most ethnic
      groups. Although there have been major advances in gene therapy technologies,
      there is still no effective cure-all gene therapy for diabetes mellitus. This may
      be due to (i) involvement of multiple genes that may have different influences on
      diabetes across different ethnic groups, (ii) immune response to viral vectors,
      (iii) local, specific transfection only and not into systemic circulation, (iv)
      lack of stable long-term expression, and (v) lack of control of gene expression.
      Hence, a separate approach to gene therapy of diabetic retinopathy is necessary
      due to the difficulties in treating the underlying diabetes. Diabetic retinopathy
      is the inevitable microvascular complication in the retina from diabetes
      mellitus. There are possible genetic bases in several pathophysiological pathways
      for diabetic retinopathy, including oxidation of retinal cells, polyol
      accumulation pathways, increased non-enzymatic glycation in retinal cells and the
      release of growth factors by endothelial cells. We review the candidate genes in
      these putative pathways for diabetic retinopathy and discuss the challenges for
      gene therapy. The eye is an isolated system with a strong blood-retinal barrier
      and therefore provides a challenge for delivery of drugs and vectors from the
      systemic circulation using traditional approaches. Newer delivery approaches
      include the use of nanoparticles, liposomes, and iontophoresis. We also consider
      the social and health economic dimension of diabetic retinopathy gene therapy.
      Diabetic retinopathy is the most common cause of blindness for people of working
      age. The loss of visual acuity caused by diabetic retinopathy creates a
      detrimental impact on the patient's quality of life. This results in quality-of
      life costs to the individual, the health care system and to society. Significant
      progress has been made in gene therapy approaches for diabetic retinopathy, and
      it appears that this is an important area for continued research in order to
      improve visual outcomes and reduce the healthcare costs of diabetic retinopathy
      in our communities.

PMID- 16611044
TI  - Cell and gene-based therapies for the lysosomal storage diseases.
AB  - Lysosomal storage disorders (LSD) are a group of approximately 40 genetic
      diseases that are caused by the deficiency of one or more lysosomal enzymes. The
      incidence of LSD is estimated to be approximately 1 in 7500 live births, which
      makes this one of the more prevalent groups of genetic diseases in humans. The
      loss in enzymatic activity leads to the accumulation of undegraded substrates
      within lysosomes, resulting in distension of the organelle and subsequent
      cellular malfunction. Although palliative treatments such as enzyme replacement
      therapy (ERT) or substrate reduction therapy (SRT) have been shown to be
      effective for some of the LSD such as Gaucher, Fabry and MPS I, they are not
      available as yet, or ineffective, for a large number of other LSD patients. To
      fulfill this unmet medical need, gene therapy is being considered as an alternate
      or adjunctive therapy for this group of disorders. A goal of gene therapy for LSD
      is to introduce a normal copy of the DNA for the lysosomal enzyme into a depot
      organ such as the liver or muscle with the intent that this will lead to the
      sustained production and re-constitution of therapeutic levels of the enzyme in
      the affected tissues. Here, we review the utility of various gene therapy
      strategies under consideration for the treatment of the LSD, including viral and
      non-viral gene transfer approaches, as well as stem cell transplantation.

PMID- 16611045
TI  - Electroporation-enhanced nonviral gene transfer for the prevention or treatment
      of immunological, endocrine and neoplastic diseases.
AB  - Nonviral gene transfer is markedly enhanced by the application of in vivo
      electroporation (also denoted electro-gene transfer or electrokinetic
      enhancement). This approach is safe and can be used to deliver nucleic acid
      fragments, oligonucleotides, siRNA, and plasmids to a wide variety of tissues,
      such as skeletal muscle, skin and liver. In this review, we address the
      principles of electroporation and demonstrate its effectiveness in disease
      models. Electroporation has been shown to be equally applicable to small and
      large animals (rodents, dogs, pigs, other farm animals and primates), and this
      addresses one of the major problems in gene therapy, that of scalability to
      humans. Gene transfer can be optimized and tissue injury minimized by the
      selection of appropriate electrical parameters. We and others have applied this
      approach in preclinical autoimmune and/or inflammatory diseases to deliver either
      cytokines, anti-inflammatory agents or immunoregulatory molecules.
      Electroporation is also effective for the intratumoral delivery of therapeutic
      vectors. It strongly boost DNA vaccination against infectious agents (e.g.,
      hepatitis B virus, human immunodeficiency virus-1) or tumor antigens (e.g., HER
      2/neu, carcinoembryonic antigen). In addition, we found that electroporation
      enhanced DNA vaccination against islet-cell antigens ameliorated autoimmune
      diabetes. One of the most likely future applications, however, may be in
      intramuscular gene transfer for systemic delivery of either endocrine hormones
      (e.g., growth hormone releasing hormone and leptin), hematopoietic factors (e.g.,
      erythropoietin, GM-CSF), antibodies, enzymes, or numerous other protein drugs. In
      vivo electroporation has been performed in humans, and it seems likely it could
      be applied clinically for nonviral gene therapy.

PMID- 16611046
TI  - Platelet signaling induced by lipoproteins.
AB  - Cardiovascular disease is the main cause of death and disability in the Western
      society. Lipoproteins play an important role in the development of this disease
      and affect different cell types involved in atherosclerosis and thrombosis. Based
      on their density, five classes of lipoproteins have been identified which all
      influence cells via distinct mechanisms. Modification turns lipoproteins into
      atherogenic particles with a prominent role in atherogenesis. The interaction of
      lipoproteins with platelets has been under investigation for a number of years.
      Especially the role of LDL in platelet signaling has been studied intensively as
      platelets of hypercholesterolemic patients are hyperreactive and show
      hyperaggregability in vitro and enhanced activity in vivo, suggesting that LDL
      enhances platelet responsiveness. Several signaling pathways induced by LDL have
      been revealed in vitro, such as signaling via p38 mitogen-activated protein
      kinase (p38MAPK) and p125 focal adhesion kinase (p125FAK). HDL opposes the
      activating properties of LDL on platelets, whereas the effects of chylomicrons,
      VLDL or IDL on platelet function are controversial. Modification of lipoproteins
      is associated with the generation of new constituents with new signaling
      properties. In particular, the platelet-activating properties of lysophosphatidic
      acid, which is a constituent of atherosclerotic plaques and is generated upon
      oxidation of LDL, have been investigated intensively. This review provides a
      summary of the activation of signaling pathways after platelet-lipoprotein
      interactions, with special emphasis on the role of these interactions in the
      development of thrombosis and atherosclerosis.

PMID- 16611047
TI  - Pathophysiology of platelet resistance to anti-aggregating agents in insulin
      resistance and type 2 diabetes: implications for anti-aggregating therapy.
AB  - The insulin resistance syndrome, which presents among its many facets obesity and
      type 2 diabetes mellitus, is a major risk factor for cardiovascular events. Thus,
      therapeutic guidelines recommend multifactorial treatment programs including,
      especially in the presence of type 2 diabetes, antiplatelet drugs. Few data,
      however, are available about the protective effect of antiplatelet therapy in
      both obese and type 2 diabetic patients. Furthermore, some reports showed a
      decreased sensitivity to the platelet antiaggregating effect of acetylsalicylic
      acid in diabetic patients. In the first part of this review, we focused our
      attention to alterations of platelets from insulin resistant subjects with or
      without type 2 diabetes, underlining that platelet hyperactivation is explained,
      at least in part, by: i) a reduced sensitivity to agents exerting an inhibitory
      modulation of platelet responses, ii) an altered intracellular milieu with
      elevated cytosolic Ca2+, iii) an enhanced thromboxane A2 synthesis, and iv) an
      increased number and/or function of GPIIb/IIIa complexes on platelet membranes.
      Furthermore, oxidative stress, which increases isoprostane production from
      arachidonic acid, may be involved in platelet hyperactivation, since isoprostanes
      activate platelets by interplaying with thromboxane receptors. These defects
      explain why antiplatelet therapy for both chronic atherosclerotic vascular
      disease and acute coronary syndromes should be specifically tailored in obese,
      insulin resistant subjects, especially in the presence of type 2 diabetes
      mellitus. Thus, in the second part of this review we carried out a critical
      overview of the clinical trials in subjects with metabolic syndrome and type 2
      diabetes mellitus with or without macroangiopathy.

PMID- 16611043
TI  - Current strategies and future directions for eluding adenoviral vector immunity.
AB  - Adenoviral (Ad) vectors can efficiently transduce a broad range of cell types and
      have been used extensively in preclinical and clinical studies for gene delivery
      applications. The presence of preexisting Ad immunity in the majority of human
      population and a rapid development of immune response against the Ad vector
      backbone following the first inoculation with the vector have impeded clinical
      use of these vectors. In addition, a number of animal inoculation studies have
      demonstrated that high systemic doses of Ad vectors invariably lead to initiation
      of acute inflammatory responses. This is mainly due to activation of innate
      immunity by vector particles. In general, vector and innate immune responses
      drastically limit the vector transduction efficiency and the duration of
      transgene expression. In order to have a predictable response with Ad vectors for
      gene therapy applications, the above limitations must be overcome. Strategies
      that are being examined to circumvent these drawbacks of Ad vectors include
      immunosuppression, immunomodulation, serotype switching, use of targeted Ad
      vectors, microencapsulation of Ad vectors, use of helper-dependent (HD) Ad
      vectors, and development of nonhuman Ad vectors. Here we review the current
      understanding of immune responses to Ad vectors, and recent advances in the
      strategies for immune evasion to improve the vector transduction efficiency and
      the duration of transgene expression. Development of novel strategies for
      targeting specific cell types would further boost the utility of Ad vectors by
      enhancing the safety, efficacy and duration of transgene expression.

PMID- 16611048
TI  - Aldosterone receptor antagonists and cardiovascular disease: do we need a change
      of the guard?
AB  - Aldosterone is a mineralocorticoid primarily produced in the zona glomerulosa of
      the adrenal gland. For many years, aldosterone (Aldo) was thought to have its
      sole site of action in the kidney, where it regulated sodium excretion and
      potassium reabsorption. It is now known that Aldo is produced in cardiovascular
      tissues, and has been implicated in the development of ventricular hypertrophy
      and cardiac fibrosis. The precise mechanisms whereby Aldo acts in cardiac tissues
      are diverse. It was assumed that Aldo production could be limited by angiotensin
      converting enzyme (ACE) inhibition, but serial measurements during therapy reveal
      only a transient decrease in Aldo levels. Moreover, the effects of Aldo on
      cardiac tissues occur even when angiotensin II (Ang II) has been suppressed or
      eliminated. Multiple investigators have examined effects of Aldo receptor
      blockade in human subjects and various animal models using the two Aldo receptor
      antagonists (ARAs), spironolactone and eplerenone. Major clinical trials
      involving spironolactone (RALES) and eplerenone (EPHESUS) ARAs have shown
      significant benefits in the treatment of congestive heart failure (CHF). In
      RALES, patients with New York Heart Association (NYHA) Class III or IV systolic
      heart failure treated with spironolactone had a 30% relative risk decrease in
      mortality. Although spironolactone is an effective competitive inhibitor of the
      mineralocorticoid receptor (MR), progestational and antiandrogenic side effects
      limit its use in some patients. Eplerenone, a more selective ARA, lacks these
      undesirable side effects. Although eplerenone is 20-fold less potent at the MR,
      it demonstrates efficacy similar to spironolactone, possibly due to decreased
      protein binding. Eplerenone has fewer side effects than spironolactone, which has
      been attributed to the low cross-reactivity with androgen and progesterone
      receptors. In EPHESUS, patients with left ventricular systolic dysfunction
      [Ejection Fraction (EF) <40%] and CHF following an acute myocardial infarction
      (AMI), were treated with eplerenone, resulting in a 17% reduction in
      cardiovascular mortality. However, these studies were limited in that diastolic
      function was not evaluated, although approximately 1/2 of CHF is due to diastolic
      dysfunction alone. To date, neither ARA has been studied for the treatment of
      diastolic dysfunction in a major clinical trial. However, numerous animal studies
      employing ARAs have shown a decrease in cardiac hypertrophy and fibrosis,
      indicating the potential benefits of these agents in the treatment of diastolic
      heart failure. In this review, we discuss possible underlying mechanisms
      responsible for Aldo effects on cardiovascular function and compare the
      beneficial effects of spironolactone and eplerenone in the treatment of heart
      disease.

PMID- 16611049
TI  - COX-inhibiting nitric oxide donors (CINODs): potential benefits on cardiovascular
      and renal function.
AB  - The COX-inhibiting nitric oxide donors (CINODs) are a new class of agents
      designed for the treatment of pain and inflammation. CINODs have a multi-pathway
      mechanism of action that involves COX inhibition and nitric oxide donation. The
      anti-inflammatory and analgesic effects of COX inhibition are reinforced through
      inhibition of caspase-1 regulated cytokine production, while nitric oxide
      donation provides multiorgan protection. Whereas both conventional nonsteroidal
      anti-inflammatory drugs (NSAIDs) and COX-2-selective NSAIDs are associated with a
      variety of adverse effects on the renal system, such as hypertension and edema,
      CINODs may offer an improved renal safety profile. These agents are devoid of
      hypertensive effects in animal models and their mechanism of action suggests that
      they may not cause edema. CINODs also have other renal-sparing effects, being
      better tolerated than NSAIDs in models of kidney failure. CINODs have been shown
      to prevent platelet activation in vitro and exhibit anti-thrombotic activity in
      vivo. In animal models of ischemia/reperfusion, CINODs treatment results in
      improved recovery of heart contractility and reduced left ventricular end
      diastolic pressure, in contrast to the effects of aspirin. The combination of
      improved analgesia, reduced gastrointestinal toxicity and cardiorenal protection
      has been established in animal models, and early clinical results suggest a
      favourable gastrointestinal safety profile in humans. The potential for CINODs to
      provide cardiorenal protection in humans is currently being investigated.

PMID- 16611050
TI  - Inflammation in cardiovascular disease and regulation of the actin cytoskeleton
      in inflammatory cells: the actin cytoskeleton as a target.
AB  - Cardiovascular disease is prevalent in developed countries causing very large
      burdens to health services. The underlying pathology is atheromatous plaque in
      the sub-endothelial region of the vascular wall. High levels of low density
      lipoprotein cholesterol and high blood pressure cause endothelial damage.
      Atheroma develop from a response to this injury that is perpetuated to chronic
      inflammation. The invasion of inflammatory leukocytes into atheroma during its
      development and in the precipitation of acute thrombotic events is mediated by
      adhesion molecules on the cell surface. These are regulated by the actin filament
      cytoskeleton which also mediates intracellular signalling from them. The actin
      cytoskeleton is central to NADPH oxidase activation that produces superoxide
      which is an intracellular signalling molecule for the hypertensive and
      inflammatory actions of angiotensin II. There are polymorphisms in actin filament
      proteins such as adducin and caldesmon and in the promoter regions of
      tropomyosins that may cause individual variation in these processes. Many
      signalling molecules in the actin filament response to inflammatory stimuli and
      in signalling downstream from actin filaments are small G-proteins that require
      post-transcriptional modification by isoprenoids from the cholesterol synthetic
      pathway. Statins deplete the isoprenoids and so down regulate G-proteins that
      mediate the inflammatory response. Angiotensin converting enzyme inhibitors and
      angiotensin II receptor type 1 antagonists decrease angiotensin II stimulated
      superoxide production thus decreasing not only blood pressure but also
      inflammation. The anti-inflammatory effects of these drugs, involving altered
      actin filament function, are a major contributor to their benefits in the
      treatment of cardiovascular disease. The feasibility of modifying the behaviour
      of actin filament proteins as a therapeutic approach for cardiovascular disease
      is considered.

PMID- 16611051
TI  - The role of thrombomodulin in atherosclerosis: from bench to bedside.
AB  - Atherosclerosis remains a leading cause of morbidity and mortality worldwide. In
      addition to the deposition of cholesterol in the arterial wall, inflammation,
      cell proliferation and migration play important roles in the pathogenesis of
      atherosclerosis. Thrombomodulin (TM) is a cell surface-expressed glycoprotein
      which is predominantly synthesized by vascular endothelial cells and a critical
      cofactor for thrombin-mediated activation of protein C. Activated protein C is
      best known for its natural anticoagulant and anti-inflammatory properties. Recent
      evidence has revealed that TM also has protein C- and thrombin-independent
      physiological function. This review summarizes recent investigations of TM,
      giving an overview on the TM unique effects on cellular proliferation, adhesion
      and inflammation, all of which are important steps in atherosclerosis. The
      current evidence of TM in the pathogenesis of atherosclerosis will be reviewed,
      and the associations of TM gene polymorphisms with atherosclerosis are presented.
      Newly emerging data of the TM in mouse atherosclerosis model demonstrates that TM
      potentially may have therapeutic role in atherosclerosis.

PMID- 16611052
TI  - Dynamics of virus-host interplay in HIV-1 replication.
AB  - HIV-1, the causative agent of AIDS, is an obligate intracellular parasite that
      has both evolved to invade the complex human system and adapted to utilize the
      host machinery for its own propagation. A dynamic interaction between the virus
      and the host systems can be observed at every step of HIV-1 life cycle. Host
      factors are involved not only for mounting antiviral responses but are also
      hijacked by the virus to assist in its replication. The host factors are
      necessary for viral replication during entry, reverse transcription, nuclear
      import, integration, transcription, nuclear export, translation, assembly and
      budding. All retroviruses including HIV-1, are species-specific and the
      replication of the retroviruses is blocked in the restrictive host by the action
      of "host restriction factors". These restriction factors act as barriers to
      retroviral replication at various stages within the infected cell of a
      restrictive host. Nevertheless, HIV-1 virus has learned to subvert these
      antiviral responses and successfully propagate within the permissive host
      environment. This review article describes identification and mechanism of action
      of several pro- and anti-HIV-1 host factors. It is likely that we are just
      beginning to get a glimpse of an ongoing complex battle between the HIV-1 and the
      host, understanding of which should provide valuable information for the
      development of novel therapeutic strategies against HIV-1.

PMID- 16611053
TI  - Retrovirus translation initiation: Issues and hypotheses derived from study of
      HIV-1.
AB  - Human immunodeficiency virus type 1 (HIV-1) has a small, multifunctional genome
      that encodes a relatively large and complex proteome. The virus has adopted
      specialized post-transcriptional control mechanisms to maximize its coding
      capacity while economically maintaining the information stored in cis-acting
      replication sequences. The conserved features of the 5' untranslated region of
      all viral transcripts suggest they are poor substrates for cap-dependent ribosome
      scanning and provide a compelling rationale for internal initiation of
      translation. This article summarizes key experimental results of studies that
      have evaluated HIV-1 translation initiation. A model is discussed in which cap
      dependent and cap-independent initiation mechanisms of HIV-1 co-exist to ensure
      viral protein production in the context of 1) structured replication motifs that
      inhibit ribosome scanning, and 2) alterations in host translation machinery in
      response to HIV-1 infection or other cellular stresses. We discuss key issues
      that remain to be understood and suggest parameters to validate internal
      initiation activity in HIV-1 and other retroviruses.

PMID- 16611054
TI  - Intracellular restriction factors in mammalian cells--An ancient defense system
      finds a modern foe.
AB  - Cross-species transmission of retroviruses poses a threat to mammalian species.
      Zoonoses have given rise to devastating diseases because the host organism is not
      prepared to resist a new pathogen. Mammals have developed several layers of
      defense against viruses, including an intracellular antiretroviral defense, a
      part of innate immunity. Retroviral restrictions had been studied for decades
      using murine leukemia virus in mice, however it has become clear that primates
      too have intrinsic mechanisms to ward off infections by retroviruses. Several of
      these antiretroviral restriction mechanisms have recently been identified, with
      two particularly well described factors being members of the tripartite motif
      (Trim) and APOBEC families. Both systems provide a strong barrier against
      lentiviral infections. The viruses have developed countermeasures that allow them
      to replicate despite the host factors. This review discusses our current
      knowledge of this ancient battle between mammalian hosts and their retroviral
      opponents.

PMID- 16611055
TI  - Viral piracy: HIV-1 targets dendritic cells for transmission.
AB  - Dendritic cells (DCs), the professional antigen presenting cells, are critical
      for host immunity by inducing specific immune responses against a broad variety
      of pathogens. Remarkably the human immunodeficiency virus-1 (HIV-1) subverts DC
      function leading to spread of the virus. At an early phase of HIV-1 transmission,
      DCs capture HIV-1 at mucosal surfaces and transmit the virus to T cells in
      secondary lymphoid tissues. Capture of the virus on DCs takes place via C-type
      lectins of which the dendritic cell-specific intercellular adhesion molecule-3
      (ICAM-3) grabbing nonintegrin (DC-SIGN) is the best studied. DC-SIGN-captured HIV
      1 particles accumulate in CD81(+) multivesicular bodies (MVBs) in DCs and are
      subsequently transmitted to CD4+ T cells resulting in infection of T cells. The
      viral cell-to-cell transmission takes place at the DC-T cell interface termed the
      infectious synapse. Recent studies demonstrate that direct infection of DCs
      contributes to the transmission to T cells at a later phase. Moreover, the
      infected DCs may function as cellular reservoirs for HIV-1. This review discusses
      the different processes that govern viral piracy of DCs by HIV-1, emphasizing the
      intracellular routing of the virus from capture on the cell surface to egress in
      the infectious synapse.

PMID- 16611056
TI  - Is autoimmunity a component of natural immunity to HIV?
AB  - Antibody neutralization would be a major way to prevent HIV infection and disease
      progression, but the complex relationship between host and pathogen makes tough
      to achieve this target through immunogens based on viral envelope proteins.
      Autoimmunity has been associated to bacterial and viral diseases, as a
      consequence of inflammatory response to pathogens; it may eventually lead to harm
      host cells and organs. However, autoimmune-like responses have also been observed
      in HIV-infected patients, raising many questions about their clinical
      significance. Recent studies have elucidated both similarities and differences
      between anti-self responses in HIV infection and autoimmune diseases, identifying
      new molecular players that might enhance immune protection to HIV and/or modulate
      the clinical progression of the established infection. This paper will present
      the current knowledge on auto-antibodies observed in HIV infection, their
      putative mechanisms of generation and their possible implications for immune
      therapy.

PMID- 16611057
TI  - Fitness constraints on immune escape from HIV: Implications of envelope as a
      target for both HIV-specific T cells and antibody.
AB  - Sterilising immunity against HIV-1 infection, whilst ideal, appears an
      unrealistic vaccination goal in the short term. More achievable is slowing the
      progression to disease and decreasing transmission by mounting strong T cell and
      neutralising antibody responses to maintain low viral loads. However, in both
      acute and chronic infection, mutant virus is selected to escape both arms of the
      adaptive immune system. Each mutation away from wildtype virus likely incurs at
      least some reduction in replicative capacity ("fitness") of the virus. Rapid
      reversion to wildtype of some immune escape mutations upon transmission, suggests
      fitness costs may be significant. HIV-1 Envelope is unique in that it is subject
      to both neutralising antibody and cell-mediated immune responses. Although
      Envelope is variable between strains, considerable serial pressure and mutational
      escape from both neutralising antibody and cytotoxic T lymphocyte attack may
      result in impaired structure and function. This could ultimately be exploited in
      HIV vaccine design.

PMID- 16611058
TI  - HAART-persistent HIV-1 latent reservoirs: their origin, mechanisms of stability
      and potential strategies for eradication.
AB  - HIV-1 infection persists despite long-term administration of highly active
      antiretroviral therapy (HAART). The mechanism of this persistence appears to
      result primarily from viral infection of CD4+ T-lymphocytes that have the ability
      to duplicate and revert into a quiescent state. These infected resting cells are
      long-lived and evade immune surveillance or clearance. The inability to eradicate
      this class of cells, bearing the viral DNA, suggests life-long persistence of
      virus in HIV-1-infected individuals, even if HAART were administered for decades.
      This review discusses the origins and mechanisms accounting for stability of
      these latent HIV-1 cellular reservoirs. It further provides an overview of recent
      clinical trials aimed at their eradication. There have been a limited number of
      immune activation (IAT) trials directed at HAART-persistent, viral reservoir
      eradication. These trials have not resulted in purging of these highly stable
      viral reservoirs though results from such efforts suggest partial effects. The
      properties of novel compounds that might be included into IAT eradication
      protocols are continuing to be evaluated and their potential for inclusion into
      future IAT trials will be discussed.

PMID- 16611059
TI  - Prevention of sexually transmitted human immunodeficiency virus (HIV) infection
      in adolescents.
AB  - Sexual behavior can threaten the physical and social well-being of young people
      in the United States in a variety of ways, as it can put them at risk for
      infection with the human immunodeficiency virus (HIV), other sexually-transmitted
      diseases (STDs) and unintended pregnancy. This review describes the current
      extent of HIV infection in American adolescents, identifies and characterizes
      particular high-risk groups and risk-bearing and protective behaviors, and
      identifies barriers to adopting preventive behaviors and using health care
      services. Our main focus is to present findings from intervention research; we
      summarize the effects of strategies that operate at the individual level (i.e.
      biomedical or behavioral, in and outside of the clinic) and environmental level
      (i.e. family, school and community behavioral) to influence behavioral change and
      the prevention of HIV infection. Overall, even though abstinence eliminates the
      risk altogether and the use of condoms can effectively reduce the risk of sexual
      transmission of HIV, adolescents do not optimally employ these practices. Various
      approaches to counseling by providers and other behavioral interventions aimed at
      reducing high-risk sexual behavior have been effective, but have met with limited
      and short-lived success. Among the areas receiving inadequate attention to date
      have been the link between biomedical and community-based behavior change
      interventions and the correspondence of biologic and behavioral outcomes. These
      areas are explored and directions for future research are suggested.

PMID- 16611060
TI  - Factors influencing adherence to highly active antiretroviral therapy in Spain.
AB  - BACKGROUND: Multiple factors have been previously described which could influence
      adherence to HAART. Our objective is to determine the fundamental factors which
      influence adherence to highly active antiretroviral therapy in our population.
      METHODS: A cross-sectional study was made selecting 143 outpatients attending our
      hospital HIV unit. 22 factors were recorded which could influence adherence to
      treatment (covering individual factors, the illness itself, the therapeutic
      regimen and the medical team). Adherence was estimated by the combination of two
      methods (self-report and pharmacy data); statistical analysis was performed using
      univariate and multivariate methods. RESULTS: 96 patients (67.13%) had good
      adherence and 47 (32.87%) did not. Only 3 of the 22 factors studied were
      significant and independent factors related with adherence: employment, housing
      situation and degree of treatment acceptance. CONCLUSIONS: we have found some
      differences regarding HAART adherence in our population compared with previous
      studies. Psychosocial and behavioral factors were the principal ones. We must try
      to detect patients at high risk of non-adherence in order to take therapeutic
      decisions properly, try to reinforce adherence and modify the factors associated
      with poor adherence.

PMID- 16611061
TI  - Deletion of the V1/V2 region does not increase the accessibility of the V3 region
      of recombinant gp125.
AB  - Previous analyses of HIV-1 surface glycoprotein indicate that both the V1/V2
      region and the interaction of gp120 with CD4 influence the accessibility of the
      V3 region on gp120. In this study we investigated the accessibility of the V3
      region of HIV-2 recombinant gp125 proteins using V3-specific mAbs (7C8 and 3C4)
      and analyzed the binding kinetics of soluble CD4 (sCD4) to recombinant HIV-1
      gp120 and HIV-2 gp125 proteins by surface plasmon resonance (SPR) analysis. Our
      results indicated that 7C8 recognized monomers of gp125 and gp125Delta v1v2,
      (lacking the V1/V2 region) while 3C4 was sensitive to the conformation of gp125,
      recognizing only oligomers of gp125Delta v1v2. Furthermore, SPR analysis of 7C8
      binding to gp125 demonstrated that the deletion of the V1/V2 region did not
      increase the accessibility of the V3 region in gp125Delta v1v2. Comparative SPR
      analyses of sCD4 binding HIV recombinant surface glycoproteins revealed a lower
      affinity of sCD4 to gp125 as compared to gp120. Moreover, the analyses suggest
      that conformational changes only occur in HIV-1 gp120 upon interaction with CD4.
      We hypothesize that the V3 region is accessible in HIV-2 gp125 and thus may not
      require interaction with CD4 to induce conformational reorientation of the V1/V2
      region.

PMID- 16611062
TI  - Takotsubo-like left ventricular dysfunction in an HIV-infected patient.
AB  - Takotsubo cardiomyopathy (in Japanese language "takotsubo" is a fishing pot with
      a round bottom and a neck that is used for trapping octopuses) is a new syndrome,
      which is characterized by transient left ventricular dysfunction and by a typical
      left ventriculogram showing transient extensive akinesis of the apical and mid
      portions of the left ventricle with hypercontraction of the basal segment, from
      which this disease takes its name. Since 1990 sporadic cases of takotsubo
      cardiomyopathy were reported by Japanese authors, and only a few European reports
      are available. We report a case of takotsubo-like left ventricular dysfunction in
      an human immunodeficiency virus (HIV)-infected caucasian patient.

PMID- 16611063
TI  - Inhibitors of HIV infection via the cellular CD4 receptor.
AB  - Recent advances in our understanding of cellular and molecular mechanisms of
      viral penetration of the target cell have provided the basis for novel
      chemotherapy and prophylaxis of HIV-1 infections. This knowledge has been
      successfully applied to the development of inhibitors that target discrete steps
      of the entry process. Interesting approaches for prevention of HIV-1 entry
      include the use of small-molecule inhibitors, natural ligands and/or monoclonal
      antibodies that interfere with gp120/CD4 interaction. Other compounds acting by
      novel mechanisms have recently been identified as anti-HIV agents and seem worthy
      of further preclinical development. Of particular interest in this regard are
      cyclotriazadisulfonamide (CADA) compounds, which down-modulate the cellular
      receptor, CD4. A series of analogues of 9-benzyl-3-methylene-1,5-di-p
      toluenesulfonyl-1,5,9-triazacyclododecane (CADA) has been synthesized and tested
      for CD4 down-modulation and anti-HIV activity. Some derivatives proved to be
      highly effective in decreasing cellular CD4 and in acting as HIV entry
      inhibitors. Three-dimensional quantitative structure-activity relationship (3D
      QSAR) studies correlating molecular features with potency have been used to
      produce a computational model. This model can be used to design more potent CD4
      down-modulating drugs for HIV therapy and prophylaxis. This review summarizes the
      results of recent studies relating to inhibitors of HIV infection via CD4 and
      discusses the therapeutic potential of targeting this cellular receptor. Special
      attention is given to our own work on small-molecule HIV entry inhibitors endowed
      with CD4 down-modulating properties.

PMID- 16611064
TI  - Natural products inhibiting the ubiquitin-proteasome proteolytic pathway, a
      target for drug development.
AB  - The ubiquitin-proteasome proteolytic pathway plays a major role in selective
      protein degradation and regulates various cellular events including cell cycle
      progression, transcription, DNA repair, signal transduction, and immune response.
      Ubiquitin, a highly conserved small protein in eukaryotes, attaches to a target
      protein prior to degradation. The polyubiquitin chain tagged to the target
      protein is recognized by the 26S proteasome, a high-molecular-mass protease
      subunit complex, and the protein portion is degraded by the 26S proteasome. The
      potential of specific proteasome inhibitors, which act as anti-cancer agents, is
      now under intensive investigation, and bortezomib (PS-341), a proteasome
      inhibitor, has been recently approved by FDA for multiple myeloma treatment.
      Since ubiquitination of proteins requires the sequential action of three enzymes,
      ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and
      ubiquitin-protein ligase (E3), and polyubiquitination is a prerequisite for
      proteasome-mediated protein degradation, inhibitors of E1, E2, and E3 are
      reasonably thought to be drug candidates for treatment of diseases related to
      ubiquitination. Recently, various compounds inhibiting the ubiquitin-proteasome
      pathway have been isolated from natural resources. We also succeeded in isolating
      inhibitors against the proteasome and E1 enzyme from marine natural resources. In
      this review, we summarize the structures and biological activities of natural
      products that inhibit the ubiquitin-proteasome proteolytic pathway.

PMID- 16611065
TI  - Sphingolipids in anticancer therapy.
AB  - Sphingolipids constitute a broad class of compounds with many biological
      functions. The sphingolipid metabolites ceramide and sphingosine are potent
      apoptosis inducers and produce cell cycle arrest, whereas sphingosine-1-phosphate
      promotes cellular growth and differentiation. Herein, the effects of
      sphingolipids and their analogs on diverse signaling pathways implicated in the
      apoptotic process are highlighted. The relatively simple chemical structure of
      these compounds has led to several strategies for their total synthesis. Those
      methods have contributed to the development and biological study of several
      analogs that present diverse degree of modification from the original structure.
      This article catalogues many of the recently developed synthetic analogs that act
      on diverse aspects of sphingolipid metabolism. A description of known enzyme
      inhibitors of the sphigolipids pathway is also given. Finally, diverse new
      sphingolipid-like antitumor agents isolated from marine sources are presented.
      This contribution opens the way for future development of new sphingolipid
      analogs that might be useful in cancer chemotherapy.

PMID- 16611066
TI  - Tangier disease four decades of research: a reflection of the importance of HDL.
AB  - Reduced circulating levels of high density lipoprotein cholesterol (HDL-C) are a
      frequent lipoprotein disorder in coronary heart disease patients and can be
      caused by either genetic and/or environmental factors (sedentary lifestyle,
      diabetes mellitus, smoking, obesity or a diet enriched in carbohydrates).
      Extremely low serum HDL-C levels occur in patients with Tangier disease (TD),
      which is caused by mutations in the adenosine triphosphate (ATP)-binding cassette
      transporter A1 (ABCA1). Clinical manifestations are related to the storage of
      cholesteryl esters in reticuloendothelial tissues and to peripheral neuropathy.
      This review focuses on the genetic and lipid abnormalities of TD, the consequence
      of these on clinical outcome and the possible treatment options. These
      abnormalities reflect the importance of HDL in the pathogenesis of vascular
      disease.

PMID- 16611067
TI  - Current strategies for modulating lymphangiogenesis signalling pathways in human
      disease.
AB  - The recent discovery that members of the vascular endothelial growth factor
      (VEGF) family of secreted glycoproteins can mediate lymphatic vessel growth
      (lymphangiogenesis) via cell surface receptor tyrosine kinases expressed on
      endothelial cells has opened the way for therapeutic intervention for pathologies
      involving dysregulated lymphatic vessel function. At least two members of this
      family, VEGF-C and VEGF-D, have been shown to induce lymphangiogenesis in vivo.
      Lymphatic vessels and their specific growth factors have been directly implicated
      in a number of significant human pathologies. In cancer, VEGF-C and VEGF-D appear
      to correlate with tumor metastasis and poor patient outcome in a range of
      prevalent human cancers. Experimental studies have demonstrated that expression
      of the lymphangiogenic growth factors in tumor models induces increased
      lymphangiogenesis and results in spread of tumor cells via the lymphatics. In
      contrast, conditions such as lymphedema, where lymphatic vessels fail to clear
      fluid from interstitial spaces, are opportunities for which the application of
      growth factors to generate new lymphatic vessels may be a viable therapeutic
      option. The list of molecules that control lymphangiogenesis is now expanding,
      allowing more opportunities for the development of drugs with which to manipulate
      the relevant signalling pathways. Modulating these pathways and other molecules
      with specificity to the lymphatic endothelium could offer alternative treatments
      for a number of important clinical conditions.

PMID- 16611068
TI  - Role of transmembrane domain/transmembrane domain interfaces of P-glycoprotein
      (ABCB1) in solute transport. Convergent information from photoaffinity labeling,
      site directed mutagenesis and in silico importance prediction.
AB  - Human P-glycoprotein (P-gp, ABCB1) plays an important role in the development of
      resistance to anticancer therapy. This ABC-transporter (ATP-binding cassette
      transporter) intercepts drugs at the level of the plasma membrane and effluxes
      them before they are able to reach their intracellular target structures.
      Inhibition of P-gp by low molecular weight compounds has been advocated as a
      concept for resensitization of cells to anticancer agents and several clinical
      studies in oncological patients have advanced to phase III. Even more
      importantly, P-glycoprotein also represents an antitarget. Its expression in
      cells lining the intestinal tract, the canalicular side of hepatocytes, renal
      tubuli and the blood brain barrier lead to interference with pharmacokinetics of
      compounds that are recognized as pump substrates. An early prediction of ADMET
      (Absorption-Distribution-Metabolism-Excretion-Toxicity) properties is important
      during drug development, since interference of a compound with P-gp might
      compromise its future development into a drug. Despite considerable efforts, the
      mechanism by which P-gp binds and transports its solutes remains unclear.
      Generation of homology models of the protein allowed integration of data obtained
      by photoaffinity labeling, in silico prediction of functional importance by
      evolutionary tracing and site directed mutagenesis. An integral view of data
      indicates that these three lines of evidence converge to indicate two
      pseudosymmetric P-gp drug binding pockets located at the two transmembrane domain
      interfaces.

PMID- 16611069
TI  - The effect of isoquinoline alkaloids on opiate withdrawal.
AB  - Our interest has been centered on isoquinoline alkaloids obtained from Argemone
      mexicana (Papaveraceae), Aristolochia constricta (Aristolochiaceae) and the opium
      alkaloid, papaverine. In this respect, the effect of these isoquinoline alkaloids
      was investigated on contractions induced by naloxone of isolated guinea pig ileum
      acutely exposed to morphine in vitro. The activity of these alkaloids was
      compared to the control compound, papaverine. Furthermore, the effect of these
      isoquinoline alkaloids was also determined on naloxone-precipitated withdrawal in
      isolated guinea pig ileum exposed to DAMGO (highly selective mu opioid receptor
      agonist) and U50-488H (highly selective kappa opioid receptor agonist) to test
      whether the possible interaction of isoquinoline alkaloids on opioid withdrawal
      involves mu- and/or kappa-opioid receptors. Isoquinoline alkaloids from A.
      mexicana (from 5 x 10(-6) to 1 x 10(-4) M), from A. constricta (1 x 10(-5) x 10(
      5)-1 x 10(-4) M) as well as papaverine treatment (1 x 10(-7)-5 x 10(-6)-1 x 10(
      6) M) before or after the opioid agonists were able of both preventing and
      reversing the naloxone-induced contraction after exposure to mu (morphine and
      DAMGO) or kappa (U50-488H) opiate receptor agonists in a concentration-dependent
      manner. Both acetylcholine response and electrical stimulation were also reduced
      by isoquinoline alkaloids and papaverine treatment as well as the final opiate
      withdrawal was still reduced. The results of the present study indicate that
      isoquinoline alkaloids as well as papaverine were able to produce significant
      influence on the opiate withdrawal in vitro and these compounds were able to
      exert their effects both at mu and kappa opioid agonists.

PMID- 16611070
TI  - Steroidal conjugates and their pharmacological applications.
AB  - Nature continues to be the main source of inspiration for synthetic chemists in
      their quest to make novel conjugates, which can have different physical,
      biological and medicinal properties. Nature makes these conjugates from mixed
      biosynthesis and some of these chimeras are found to exhibit unusual biological
      properties. During the past two decades design of such entities has been
      receiving increasing attention. Among the hybrid natural products, hybrids of
      steroid frameworks have attracted great attention due to the significant
      biological properties and numerous therapeutic effects of steroids. The
      developments made over the past few years in the isolation, design and synthesis
      of steroidal conjugates and their pharmacological applications are discussed in
      this review.

PMID- 16611071
TI  - Antiangiogenesis drug design: multiple pathways targeting tumor vasculature.
AB  - The initiation, growth, and development of new blood vessels through angiogenesis
      are essential for tumor growth. Tumor masses require access to blood vessels for
      a sufficient supply of oxygen and nutrients to maintain growth and metastasis.
      Inhibiting tumor blood vessel formation as proposed by Judah Folkman in the early
      1970s, therefore, offers promising therapeutic approaches for treating tumor
      afflicted patients. The blood vessel growth in normal tissues is regulated though
      a delicate and complex balance between the collective action of proangiogenic
      factors (e.g., vascular endothelial growth factor, VEGF) and the collective
      action of angiogenic inhibitors (e.g., thrombospondin-1). In pathological
      angiogenesis, the angiogenic switch is shifted toward the proangiogenic factors,
      and if the imbalance continues, irregular tumor vessel growth is the result.
      Despite intense research, the mechanism of the angiogenic switch is not fully
      understood. Many factors, however, have been shown to be involved in regulating
      the equilibrium between angiogenic stimulants and inhibitors. VEGFR tyrosine
      kinase, methionine aminopeptidase-2 (MetAP-2), p53, tubulin, cyclooxygenase-2
      (COX-2), and matrix metalloproteinases (MMPs) all directly and/or indirectly
      influence the angiogenic switch. This review will describe some of the advances
      in inhibitor design and the mechanisms of action for the aforementioned factors
      (targets) involved in angiogenesis regulation. Our discussion reveals that a
      diaryl group separated by various connecting modules is one of the most common
      features for antiangiogenesis drug design. This idea has been a working
      pharmacophore hypothesis for our own antiangiogenic drug design endeavors over
      the years. The recent advances of combination therapy (angiogenesis inhibitors
      with other chemotherapy/radiation) are also discussed.

PMID- 16611072
TI  - Destroying RNA as a therapeutic approach.
AB  - The ability to target RNA, mRNA and viral RNA in particular, for degradation is a
      powerful approach in molecular biology and pharmacology. Such approaches can be
      used in the study of gene function as in functional genomics, in the
      identification of disease-associated genes, and for the treatment of human
      diseases. This review provides a comprehensive up-to-date look at all the current
      available technologies used for the destruction of RNA, with a focus on their
      therapeutic potential. This includes approaches that utilize the activity of
      protein ribonucleases such as antisense oligonucleotide, small interfering RNA,
      RNase P-associated external guide sequence, onconase and bovine seminal RNase.
      Sequence-specific approaches that do not utilize activity of protein
      ribonucleases, such as ribozyme and DNazyme, are also reviewed and discussed.
      This review should provide a useful starting framework for researchers interested
      in using the RNA-destruction methodologies on the bench and in the clinic, and
      serves as a stimulus for further development of novel and more potent RNA
      degradation technologies. This is particularly critical, given the anticipation
      of discoveries of new cellular RNA degradation machineries and human diseases
      that are associated with dysfunctional RNA molecules.

PMID- 16611074
TI  - Luminescent quantum dots: a very attractive and promising tool in biomedicine.
AB  - Luminescent semiconductor nanocrystals, also known as quantum dots (QDs), are
      generally composed of II-VI and III-V elements. Due to their quantum confinement
      of charge carriers in tiny spaces, QDs show some unique and fascinating optical
      properties, and are characterized as sharp and symmetrical emission spectra, high
      quantum yields, broad absorption spectra, good chemical and photo-stability and
      size dependent emission wavelength tunability. Recently, QDs have been
      successfully used as new fluorescent tags in many biological and biomedical
      fields, and will become a new promising tool in biomedical studies, clinical
      diagnostics, drug delivery and photodynamic therapy. In this review, firstly, the
      methodology of QDs preparation was introduced, which included organic synthesis,
      aqueous synthesis and microwave assisted aqueous synthesis. Secondly, some
      procedures for the QDs bio-conjugation with biomarkers were described. And then,
      some key applications of QDs were summarized, which mainly covered biomedical
      imaging, immunoassay, DNA hybridization, and photodynamic therapy. Finally,
      future prospects were discussed.

PMID- 16611075
TI  - The HIV entry inhibitors revisited.
AB  - The new generation of antiviral drugs intended to counter HIV-1 entry into
      susceptible cells is emerging swiftly. The antiviral agents that inhibit HIV
      entry to the target cells (denoted as HIV entry inhibitors) are already in
      different phases of clinical trials. Operating early in the viral life cycle,
      they prevent viral entry, and have a novel, highly specific mechanism of action
      with a low toxicity profile. Entry inhibitors have different toxicity and
      resistance profiles than the existing reverse transcriptase and protease
      inhibitors. Some of these compounds demonstrated in vitro synergism with other
      classes of antivirals, thus offering the rationale for their combination in
      therapies for HIV-infected individuals. It is worth focusing on recent
      developments in HIV entry inhibitors, as most of the current drug regimens suffer
      from the events of developing resistance against existing combination therapies.
      Recent advances in the understanding of the cellular and molecular mechanisms of
      HIV-1 entry provide the basis for novel therapeutic strategies that prevent viral
      penetration of the target cell-membrane, while reducing detrimental virus and
      treatment effects on cells and prolonging virion exposure to immune defenses. A
      number of potential sites for therapeutic intervention become accessible during
      the narrow window between virus attachment and the subsequent fusion of viral
      envelope with the cell membrane. The HIV-1 coreceptors are particularly
      attractive from the perspective of identifying new antiviral compounds, since
      they are seven-transmembrane motif G protein-coupled receptors (GPCRs), a family
      of proteins that is a well-validated target for drug development. Among the many
      chemokine receptors that can mediate HIV-1 entry in vitro, only CCR5 and CXCR4
      are of frontline pharmacological importance. In particular, CCR5 is essential for
      viral transmission and replication during the early and clinically latent phase
      of disease. Several small-molecule antagonists of CCR5 and CXCR4 that block
      chemokine binding and HIV-1 entry have been identified in recent years.
      Considerable advances have been made in the last years in the design of
      derivatives acting as inhibitors of HIV entry. The molecular mechanism involved
      in viral entry, the structural and functional aspects of entry inhibitors are
      reviewed here. We have also summarized the recent insights into how small
      molecule antagonists interact with CCR5 and CXCR4, focusing on drug development
      programs that are well documented in the scientific literature. An overview of
      the entry inhibitors that are in preclinical or early clinical development, and
      the Quantitative Structure-Activity Relationships (QSAR) studies reported for the
      coreceptor antagonists are also be presented.

PMID- 16611076
TI  - Epigenetic control using natural products and synthetic molecules.
AB  - The term "epigenetics" is defined as "heritable changes in gene expression that
      occur without changes in DNA sequence". Recently, it has been revealed that DNA
      methylation and histone modifications such as acetylation, methylation and
      phosphorylation are epigenetic mechanisms according to this definition. In other
      words, these posttranslational modifications are important factors in determining
      when and where a gene will be expressed. To date, several enzymes that catalyze
      DNA or histone modifications have been identified, such as DNA methyltransferases
      and histone deacetylases. Inhibitors and activators of enzymes controlling
      epigenetic modifications are considered useful not only as tools for the
      elucidation of cellular and biological phenomena, but also as therapeutic agents,
      since disruption of the balance of epigenetic networks is known to cause some
      disease states such as cancer. In this review, we present natural products and
      synthetic molecules that inhibit or activate enzymes catalyzing DNA methylation
      or histone modifications, and discuss the potential of epigenetic therapy.

PMID- 16611077
TI  - Application of radioisotopes in inflammation.
AB  - Since the discovery of artificially produced radioisotopes in the 1930's, an
      estimated 10-12 million nuclear medicine diagnostic and therapeutic procedures
      are currently performed each year only in the United States. Gamma emission
      imaging has been successfully applied to almost every organ of the body (brain,
      bone, heart, kidney, lung, neuroreceptors) as well as sites of inflammation,
      atherosclerosis, and thrombosis. FDG-PET has been used in some of the
      inflammatory diseases as well. On the other hand, both alpha- and beta-emitting
      isotopes have been evaluated for brachytherapy of rheumatoid diseases, each with
      different radiobiological effectiveness. The current status of radionuclides for
      imaging, therapy and research studies of inflammatory processes is reviewed here
      and a look into the future directions is described at the conclusion.

PMID- 16611078
TI  - Inhibition of fatty acid synthase by polyphenols.
AB  - Recently, animal fatty acid synthase (FAS) is reported as a potential therapeutic
      target for obesity and cancer. Considerable interest has been developed in
      identifying novel inhibitors of the enzyme. It is found that tea polyphenols
      inhibit FAS in both reversible and irreversible manners. Epigallocatechin gallate
      (EGCG) and epicatechin gallate (ECG) inhibit FAS with IC(50) values of 52 microM
      and 42 microM mainly by reacting on the beta-ketoacyl reductase (KR) domain of
      FAS. The inhibitory ability of catechin gallate (CG) is 15 and 12 folds higher
      than that of EGCG and ECG. Its major reacting site on FAS is not KR. All of these
      irreversibly inactivate FAS on the KR domain with similar rates. Mulliken
      population analysis suggests that the positive charge is distributed on the
      carbon atom of galloyl ester, and this carbon becomes more susceptible for a
      nucleophilic attack. 12 flavonoids inhibit FAS with IC(50) values ranging from 2
      to 112 microM. SAR analysis shows that the flavonoids containing two hydroxyl
      groups in B ring and 5, 7-hydroxyl groups in A ring with C-2, 3 double bond are
      the most potent inhibitors. The inhibition kinetics shows that they inhibit FAS
      competitively with acetyl CoA and most likely react mainly on acyl transferase
      domain. Further studies show that C ring of flavonoids is not necessary for the
      inhibition. Resveratrol, phlorizin and NDGA contain two phenyl rings connected by
      2 to 4 atom chains instead of C ring. Their IC(50) values range from 5 microM to
      40 microM. From these results, a common model for polyphenol inhibitor of FAS is
      conceived.

PMID- 16611073
TI  - Cell Life versus cell longevity: the mysteries surrounding the NAD+ precursor
      nicotinamide.
AB  - Nicotinamide, the amide form of niacin (vitamin B(3)), is the precursor for the
      coenzyme beta-nicotinamide adenine dinucleotide (NAD(+)) and plays a significant
      role during the enhancement of cell survival as well as cell longevity. Yet,
      these abilities of nicotinamide appear to be diametrically opposed. Here we
      describe the development of nicotinamide as a novel agent that is critical for
      modulating cellular metabolism, plasticity, longevity, and inflammatory
      microglial function as well as for influencing cellular life span. The capacity
      of nicotinamide to govern not only intrinsic cellular integrity, but also
      extrinsic cellular inflammation rests with the modulation of a host of cellular
      targets that involve mitochondrial membrane potential, poly(ADP-ribose)
      polymerase, protein kinase B (Akt), Forkhead transcription factors, Bad,
      caspases, and microglial activation. Further knowledge acquired in regards to the
      ability of nicotinamide to foster cellular survival and regulate cellular
      lifespan should significantly promote the development of therapies against a host
      of disorders, such as aging, Alzheimer's disease, diabetes, cerebral ischemia,
      Parkinson's disease, and cancer.

PMID- 16611079
TI  - Pharmaceutical interventions to influence arteriogenesis: new concepts to treat
      ischemic heart disease.
AB  - Despite the technical progress in interventional techniques to overcome the
      harmful effects of ischemic heart disease there is still an urgent need for
      alternative, pharmaceutical treatment modalities. Exogenous stimulation of vessel
      growth, i.e. vasculogenesis, angiogenesis or arteriogenesis serves as a promising
      strategy to restore blood flow to the jeopardized tissue regions downstream of
      arterial stenosis or occlusion. While vasculogenesis is defined as the
      arrangement of angioblasts during prenatal development creating the first
      vascular network, angiogenesis and arteriogenesis refer to important adaptive
      mechanisms in the adult organism. Angiogenesis, neo-formation of capillaries, is
      a key process in many different physiological and pathophysiological events where
      improvement of microvascular function and tissue nutrition is needed (e.g. wound
      healing, tumor growth). In contrast to this capillary sprouting, the term
      arteriogenesis refers to the development of large caliber collateral arteries.
      Under conditions of increasing shear stress, anastomoses between interconnected
      perfusion territories can undergo adaptive enlargement, developing into a
      functional network of collateral arteries, natural bypasses able to maintain
      sufficient blood flow and compensating for the gradual occlusion of a large
      artery (e.g. in the coronary circulation). However, in most cases arteriogenesis
      does not proceed as fast as the stenosis progresses and infarction and tissue
      necrosis results. A well-developed collateral network is an important protective
      factor for the occurrence of ischemic events and therefore pharmaceutical
      acceleration and stimulation of arteriogenesis in patients represents an eminent
      aim for the future. This review focuses on the basic mechanisms of
      arteriogenesis, the recent progresses in translating these insights into the
      clinical situation and the problems yet to be solved.

PMID- 16611081
TI  - Bile acid reabsorption inhibitors (BARI): novel hypolipidemic drugs.
AB  - The enterohepatic circulation of bile acids is a major regulator of serum
      cholesterol homeostasis. After biosynthesis from cholesterol in the liver, bile
      acids are secreted with bile into the lumen of the small intestine to aid in the
      digestion and absorption of fat and fat-soluble vitamins. The bile acids are
      nearly quantitatively reabsorbed in the terminal ileum by a Na+-dependent
      transport system (IBAT) and are transported with portal blood to the liver and
      taken up by a second Na+-/bile acid cotransporter (LBAT) to be resecreted into
      bile. In the liver bile acids inhibit the rate-limiting enzyme for the conversion
      of cholesterol into bile acid: cholesterol-7alpha-hydroxylase; interruption of
      the enterohepatic circulation of bile acids withdraws this feedback inhibition
      and leads to an upregulation of hepatic LDL-receptors with a concomitant decrease
      of serum LDL-levels. Specific inhibitors of the ileal bile acid transporter
      belonging to different chemotypes have been developed in recent years for this
      purpose, some now entering clinical stage. To exert a profound systemic effect
      these compounds do not need to be available systemically but can act from the
      luminal side of the small intestine, which offers the advantage to avoid the well
      known adverse side effects of other hypolipidemic drugs like statins due to
      metabolism and drug-drug interactions in the liver. This implies several aspects
      in compound optimization and drug development quite different from standard
      procedures, for example the concept of low absorption drugs was established to
      avoid systemic side effects. The review article covers the mechanistic and
      therapeutic principles of the approach and presents an overview on the molecular
      target, the discovery of specific inhibitors and respective optimization
      strategies.

PMID- 16611082
TI  - Glycine transporter type-1 and its inhibitors.
AB  - The ionotropic glutamate receptor NMDA is allosterically modulated by glycine, a
      coagonist, its presence is an absolute requirement for receptor activation. The
      transport of glycine in glutamatergic synapse is carried out by glycine
      transporter-1 (GlyT1), a Na+/Cl(-)-dependent carrier molecule. The primary role
      of GlyT1 is to maintain glycine concentrations below saturation level at
      postsynaptic NMDA receptors. Several isoforms of GlyT1 (a-e) have been
      identified, which are expressed both in glial and neuronal cell membranes. GlyT1
      operates bidirectionally: it decreases synaptic glycine concentration when
      operates in normal mode and releases glycine from glial cells as operates in a
      reverse mode. It is expected that non-transportable, non-competitive inhibitors
      of GlyT1 may have therapeutic value in CNS disorders characterized by
      hypofunctional NMDA receptor-mediated glutamatergic neurotransmission.
      Accordingly, GlyT1 inhibitors exhibited antipsychotic profile in a number of
      animal tests. The first promising in vitro and in vivo experiments with glycine
      itself, and its N-methyl analogue, sarcosine, had initiated the syntheses of
      potential GlyT1 inhibitors with more complex structures, in which, however, the
      glycine or sarcosine moiety had always been incorporated. Those attempts led to
      the development of two compounds, ALX-5407 and Org-24461 with high inhibitory
      potency; however, none of which is now considered as a drug candidate due, most
      probably, to safety and/or pharmacokinetic issues. More recently, several
      structurally new series of highly potent inhibitors with no aminomethylcarboxy
      group have also been discovered. Some of them might be expected to fulfill all
      requirements for clinical development. The new generation of GlyT1 inhibitors may
      represent a novel treatment of patients suffering from schizophrenia and/or other
      neuropathological conditions.

PMID- 16611080
TI  - Vascular dysfunction in aging: potential effects of resveratrol, an anti
      inflammatory phytoestrogen.
AB  - Epidemiological studies demonstrated that even in the absence of other risk
      factors (e.g. diabetes, hypertension, hyperhomocysteinemia,
      hypercholesterolemia), advanced age itself significantly increases cardiovascular
      morbidity by enhancing vascular oxidative stress and inflammation. Because the
      population in the Western world is rapidly aging, there is a substantial need for
      pharmacological interventions that delay the functional decline of the
      cardiovascular system. Resveratrol is an atoxic phytoestrogen found in more than
      70 plants including grapevine and berries. Recent data suggest that nutritional
      intake of resveratrol and other polyphenol compounds may contribute to the
      "French paradox", the unexpectedly low cardiovascular morbidity in the
      Mediterranean population. There is increasing evidence that resveratrol exerts
      multifaceted anti-oxidant and/or anti-inflammatory effects in various disease
      models. Importantly, resveratrol was reported to slow aging and increase lifespan
      in simple organisms and has been suggested as a potential calorie restriction
      mimetic. Resveratrol has also been reported to activate NAD-dependent histone
      deacetylases (sirtuins), which may contribute to its anti-aging effects. This
      review focuses on the role of oxidative stress and inflammation in cardiovascular
      dysfunction in aging, and on emerging anti-aging therapeutic strategies offered
      by resveratrol and other polyphenol compounds.

PMID- 16611083
TI  - Carboxylesterases--detoxifying enzymes and targets for drug therapy.
AB  - Carboxylesterases (CE) are ubiquitous enzymes responsible for the detoxification
      of xenobiotics. Many therapeutically useful drugs are metabolized by these
      proteins which impacts upon the efficiency of drug treatment. In some instances,
      CEs convert inactive prodrugs to active metabolites, a process that is essential
      for biological activity. Such compounds include the anticancer agents CPT-11 (3)
      and capecitabine (4), the antibiotics Ceftin (9) and Vantin, as well as the
      illicit street drug heroin (6). However, more commonly, CEs hydrolyze many
      esterified drugs to inactive products that are then excreted. Agents such as
      flestolol (11), meperidine (5), lidocaine (8) and cocaine (7), are all hydrolyzed
      and inactivated by these enzymes. Therefore the efficacy of esterified drugs will
      be dependent upon the distribution and catalytic activity of different CEs. In
      this review, we examine the structural aspects of CEs and their roles in drug
      detoxification and propose that modulation of CE activity may allow for
      improvements in, and potentiation of, drug efficacy.

PMID- 16611084
TI  - Silymarin as a new hepatoprotective agent in experimental cholestasis: new
      possibilities for an ancient medication.
AB  - Silymarin is a purified extract from milk thistle (Silybum marianun (L.) Gaertn),
      composed of a mixture of four isomeric flavonolignans: silibinin (its main,
      active component), isosilibinin, silydianin and silychristin. This extract has
      been empirically used as a remedy for almost 2000 years, and remains being used
      as a medicine for many types of acute and chronic liver diseases. Despite its
      routinely clinical use as hepatoprotectant, the mechanisms underlying its
      beneficial effects remain largely unknown. This review addresses in detail a
      number of recent studies showing a novel feature of silymarin as a
      hepatoprotective drug, namely: its anticholestatic properties in experimental
      models of hepatocellular cholestasis with clinical correlate. For this purpose,
      this review will cover the following aspects: 1. The chemistry of silymarin,
      including chemical composition and properties. 2. The current clinical
      applications of silymarin as a hepatoprotective agent, including the mechanisms
      by which silymarin is thought to exert its hepatoprotective properties, when
      known. 3. The physiological events involved in bile formation, and the mechanisms
      of hepatocellular cholestasis, focusing on cellular targets and mechanisms of
      action of drugs used to reproduce experimentally cholestatic diseases of clinical
      interest, in particular estrogens and monohydroxylated bile salts, where
      anticholestatic properties of silymarin have been tested so far. 4. The recent
      findings describing the impact of silymarin on normal bile secretion and its
      novel, anticholestatic properties in experimental models of cholestasis, with
      particular emphasis on the cellular/molecular mechanisms involved, including
      modulation of bile salt synthesis, biotransformation/depuration of cholestatic
      compounds, changes in transporter expression/activity, and evocation of signaling
      pathways.

PMID- 16611085
TI  - Oxidative stress in Alzheimer patients in different stages of the disease.
AB  - Increasing evidence demonstrates that oxidative stress causes damage to cell
      function with aging and is involved in a number of age-related disorders
      including atherosclerosis, arthritis, and neurodegenerative disorders. Cellular
      changes show that oxidative stress is a condition that precedes the appearance of
      the hallmark pathologies of the disease, neurofibrillary tangles and senile
      plaques. The aim of this article is to analyze the different biomarkers of
      oxidative stress in Alzheimer patients, in different stages of the illness, and
      compare the results with a control group. A nutritional evaluation was carried
      out, including anthropometric and biological measures and a 3 day dietary record.
      The concentration of substances which react to thiobarbituric acid (TBARS) was
      measured as a marker of the degree of peroxidation using the HPLC method. The
      oxidation of proteins was analyzed by measuring the carbonyl groups in plasma. In
      addition, measurements were made of the total antioxidant activity in plasma and
      the activity of endogenous antioxidant enzymes such as gluthatione peroxidase,
      gluthatione reductase and superoxide dismutase. The total antioxidant plasmatic
      status of the patients with Alzheimer both in light-moderate phase and in
      advanced phase was lower than in the control. No significant differences were
      observed between the different stages of the disease in protein oxidation levels.
      Peroxidation was higher in patients in the advanced stage of the disease than in
      the control group. However, no significant differences were observed between the
      different stages of the disease. In this preliminary study, it was observed that
      Alzheimer patients in the light-moderate stage already present oxidative stress
      levels above those of the control group.

PMID- 16611086
TI  - Ruthenium complexes as anticancer agents.
AB  - Cancer is one of the major cases of death in the world. Current treatment of
      cancer is limited to surgery, radiotherapy, and the use of cytotoxic agents,
      despite their well known side effects and problems associated with the
      development of resistance. For most forms of disseminated cancer, however, no
      curative therapy is available, and the discovery and development of novel active
      chemotherapeutic agents is largely needed. Since the development of cisplatin, an
      inorganic platinum complex, numerous platinum and non-platinum metal complexes
      were synthesized and tested for anticancer activity. Very few match the clinical
      efficacy of cisplatin. Ruthenium complexes were prepared to ameliorate cisplatin
      activity, particularly on resistant tumours, or to reduce host toxicity at active
      doses. Since many years a lot of scientific groups have actively worked in the
      field of inorganic antitumor drugs and have developed a number of Ru(II) and
      Ru(III) complexes, which were shown to possess good antitumor and, above all,
      antimetastatic properties against animal models. Ruthenium complexes are
      presently an object of great attention in the field of medicinal chemistry, as
      antitumor agents with selective antimetastatic properties and low systemic
      toxicity. Ruthenium compounds appear to penetrate reasonably well the tumor cells
      and bind effectively to DNA. In this review, the achievements in the field of
      medicinal chemistry, DNA binding modes, and the development status of Ru(II) and
      Ru(III) complexes as anticancer agents are discussed. The aim of this review is
      therefore that of critically examining the past and the actual work on ruthenium
      compounds with emphasis on their proposed role in cancer therapy.

PMID- 16611088
TI  - Neuropeptides in psychiatric diseases: an overview with a particular focus on
      depression and anxiety disorders.
AB  - This paper aimed at reviewing the involvement of neuropeptides in various
      psychiatric diseases, particularly in depression, and anxiety disorders. General
      features of neuropeptides are first described, including the history of their
      discovery, their definition, classification, biosynthesis, transport, release,
      inactivation, as well as their interaction with specific neuronal receptors. The
      differences with classical neurotransmitters are mentioned, as well as the
      different patterns of co-transmission. Finally, different mechanisms, both at the
      cellular and at the systemic level, are proposed that may explain the involvement
      of these molecules in various psychiatric diseases. Indeed, at the cellular
      level, a neuropeptide can be involved in a psychiatric disease, either because it
      is co-localized with a classical neurotransmitter involved in a disease, or
      because the neuropeptide-containing neuron projects on a target neuron involved
      in the disease. At the systemic level, a neuropeptide can play a direct role in
      the expression of a symptom of the disease. This is illustrated by different
      examples.

PMID- 16611089
TI  - Corticotropin-releasing factor receptor antagonists in affective disorders and
      drug dependence-- an update.
AB  - Dysfunctioning of corticotropin-releasing factor (CRF) and its receptors (CRF(1)
      and CRF(2)) has been linked to the development of stress-related disorders, such
      as affective disorders and drug abuse. The molecular characterization of CRF(1)
      and CRF(2) receptors and their splice variants has generated detailed information
      on their pharmacology, tissue distribution and physiology. In addition, the
      recent development of a small molecule CRF(1) antagonist has provided important
      information on the contribution of this receptor to the development of stress
      related diseases. Despite the high homology to the CRF(1) receptor and the
      generation of peptide-based research tools, the physiological role of the CRF(2)
      receptor is largely unclear. This is due to different expression patterns in
      rodents and primates and the lack of brain-penetrant CRF(2)-selective small
      molecule antagonists. However, the CRF(2) receptor may be important for
      motivational types of behavior essential for survival, such as feeding and
      defense and impacts on cardiovascular function.

PMID- 16611090
TI  - The involvement of the vasopressin system in stress-related disorders.
AB  - The neuropeptide arginine vasopressin (AVP) is released within distinct brain
      areas upon appropriate stimulation, including stressful challenges. Following its
      predominantly dendritic release, AVP triggers a variety of receptor-mediated
      effects related to behavioral and neuroendocrine regulation. Antagonist treatment
      together with other sophisticated loss-of-function and gain-of-function
      approaches provide evidence for a multiple involvement of V1a and V1b receptor
      subtypes in stress-related behavior and disorders, including anxiety disorders,
      comorbid depression and their neuroendocrine concomitants. Conversely, in the
      high versus low anxiety (HAB/LAB) rat model, the phenotype of extreme trait
      anxiety is associated with a polymorphism-driven overexpression of AVP in the
      hypothalamic paraventricular nucleus. This overexpression of AVP might be
      considered a final common pathway of anxiety-related behavior. The capability of
      both responding to stressful stimuli and mediating genetic polymorphisms makes
      the central release of AVP a key process for converging (i.e., environmentally
      and genetically driven) behavioral regulation. Polymorphisms in the promoter
      structures of the AVP gene and AVP receptor genes, underlying differences in gene
      expression, thus contribute to individual variation in behavior as well as to
      psychopathology, making genes of the brain AVP system and their products a
      promising target for therapeutic interventions.

PMID- 16611091
TI  - Neuropeptide y: role in emotion and alcohol dependence.
AB  - Neuropeptide Y (NPY) is considered to be an important neuromodulator in the
      regulation of emotional behavior. For example, NPY is consistently involved in
      anxiety-related behaviors and there is increasing support for a role of this
      peptide in mood disorders such as depression. Furthermore, recent evidence
      suggests that NPY has a significant role in the neurobiological response to
      alcohol, including alcohol consumption, dependence, and withdrawal. In addition,
      NPY is beginning to emerge as an important modulator in the etiology of
      alcoholism that is independent from the addictive and reinforcing properties of
      the traditional system commonly associated with dopamine and instead, is strongly
      associated with innate emotionality. The recent developments elucidating the role
      of NPY in emotion and alcohol dependence are reviewed and the potential of the
      NPY system as a novel therapeutic strategy in the treatment of anxiety,
      depression and alcohol-related disorders is examined.

PMID- 16611092
TI  - Gastrin-releasing peptide receptor as a molecular target for psychiatric and
      neurological disorders.
AB  - The mammalian bombesin (BB)-like peptide gastrin-releasing peptide (GRP)
      stimulates cell proliferation, displays a range of neuroendocrine activities, and
      acts as a growth factor in the pathogenesis of several types of human cancer.
      Several lines of evidence have indicated that GRP and its receptor (GRPR) might
      also be involved in the neurochemical alterations associated with psychiatric and
      neurological disorders. GRP and GRPR are distributed throughout the mammalian
      central nervous system (CNS). Altered levels of BB-like peptides have been found
      in the CNS of patients with schizophrenia and Parkinson's disease. Dysfunctions
      in GRPR-induced cellular calcium signaling have been reported in fibroblasts from
      patients with Alzheimer's disease. A translocation in the GRPR gene has been
      associated with autism. Pharmacological and genetic studies in rodents have shown
      that GRPRs in brain areas such as the dorsal hippocampus and amygdala are
      importantly involved in regulating synaptic plasticity and aspects of behavior
      that might be altered in disorders such as anxiety, schizophrenia, depression,
      autism and dementia. Behaviors modulated by the GRPR in rodents include grooming,
      food intake, stereotypy, social behavior, and emotionally-motivated learning and
      memory. Together, these findings support the view that the GRPR should be
      considered a therapeutic target for a subset of CNS diseases.

PMID- 16611093
TI  - Novel treatments of schizophrenia: targeting the neurotensin system.
AB  - Evidence implicating neural circuits that utilize the neuropeptide transmitter
      neurotensin (NT) in the pathophysiology of schizophrenia and in the mechanism of
      action of antipsychotic drugs has previously been reviewed. The majority of
      evidence, taken together, supports the development of NT receptor agonists as
      novel antipsychotic drugs. This review comprehensively describes the NT receptor
      subtypes, discusses the development of NT receptor agonists and the behavioral
      effects of currently available NT receptor agonists. The compilation of data
      suggests that NT receptor agonists may represent a novel class of antipsychotic
      drugs for the treatment of schizophrenia.

PMID- 16611094
TI  - The Orphanin FQ / Nociceptin receptor as a novel drug target in psychiatric
      disorders.
AB  - Almost 10 years after the discovery of Orphanin FQ / Nociceptin (OFQ/N) a large
      number of synthetic small molecule agonists and antagonists have been developed
      and tested in various physiological assays. Together with the academic work on
      the physiological functions of OFQ/N, we now have compelling evidence that this
      neuropeptide system might represent a valuable target for the development of
      drugs treating a variety of psychiatric disorders. Most prominently, the anti
      stress and anxiolytic effects of OFQ/N agonists have been investigated although
      clinical trials have not yet been launched. Other possible applications of OFQ/N
      agonists and antagonists include treatment of depression, anorexia and rewarding
      aspects of drug addiction. This paper will summarize current developments and
      highlight the scientific achievements that have been made to elucidate the
      functions of OFQ/N with respect to psychiatric disorders.

PMID- 16611095
TI  - Galanin: a novel therapeutic target for depression, anxiety disorders and drug
      addiction?
AB  - Galanin is a neuropeptide synthesized in many neuronal types including brainstem
      norepinephrine-producing cells of the locus coeruleus and the serotonin-producing
      neurons of the dorsal raphe nucleus. Galanin inhibits the firing of rodent
      norepinephrine, serotonin and dopamine neurons and reduces release of these
      neurotransmitters in forebrain target regions. The distribution of galanin and
      its receptors and its actions on monoamine signaling has fostered interest in
      this neuropeptide in the field of behavioral pharmacology and the potential role
      of galanin in the pathophysiology of neurological diseases such as Alzheimer's
      disease, epilepsy, stroke, and in psychiatric disorders such as anxiety,
      depression, and drug addiction, particularly withdrawal. In rodent models,
      expression of galanin in brain is altered by various stressors, while
      administration of galanin can modulate anxiety-like responses to stress. Emerging
      evidence further supports a role for galanin in the mediation of depression
      related behaviors in rodents. Recently, galanin agonists have been shown to
      decrease behavioral signs of opiate withdrawal, which are thought to result from
      hyperactivation of brain stress pathways. Studies using genetically modified mice
      suggest that galanin normally plays a protective role against opiate
      reinforcement and withdrawal. The present article reviews current evidence on a
      potential role for galanin in modulating stress-related neural pathways and
      behaviors, and speculates on the therapeutic potential of targeting this galanin
      system for emotional disorders and opiate addiction.

PMID- 16611096
TI  - Alcoholism and neuropeptides: an update.
AB  - As with other addictions, human alcoholism is characterised as a chronically
      relapsing condition. Consequently, the "holy grail" from a therapeutic viewpoint
      is the development of clinically effective, safe drugs that promote high
      compliance rates and prevent relapse. Here we discuss the potential of
      therapeutics targeting neuropeptide systems implicated in aberrant alcohol
      seeking behaviour. Clearly, much of the data so far available comes from pre
      clinical studies; however, one of the first effective therapeutic strategies for
      alcoholism (still in use today) was the use of non-selective opioid receptor
      antagonists, such as naltrexone (Revia). In addition to opioid receptors, other
      neuropeptide receptors including those for corticotrophin releasing factor (CRF),
      neuropeptide Y and nociceptin may represent valid therapeutic targets to regulate
      alcohol consumption and the affective consequences of alcohol withdrawal.

PMID- 16611098
TI  - Introduction: hereditary hemorrhagic telangiectasia as a rare disease.
AB  - A disease is considered rare in the United States when it affects one individual
      per 1, 250 and one individual per 2,000 in Europe. Most rare diseases (RD) are of
      genetic origin; their rarity involves a difficult and/or late diagnosis. The
      greatest barrier to prevention, diagnosis and treatment of RD is inadequate
      knowledge. Hereditary haemorrhagic telangiectasia (HHT) is a "rare" genetic
      disorder that is becoming more commonly recognised. Recent evidence indicates
      that it is more frequent (1-2/10,000) than previously estimated. We suppose that
      the frequent misdiagnosis and the different genetic penetrance have led to an
      underestimation of real prevalence. In fact, progress in scientific knowledge and
      improvement in diagnostic and therapeutic technologies has unmasked conditions
      which were not fully known previously, determining a fictitious decrease in
      disease frequency.

PMID- 16611099
TI  - Hereditary Haemorrhagic Telangiectasia (HHT): genetic and molecular aspects.
AB  - Hereditary Haemorrhagic Telangiectasia, or Rendu-Osler-Weber syndrome, is a rare
      autosomal dominant disorder involving the vascular system and is characterised by
      a highly variable expressivity and age-dependent penetrance. Diagnosis is based
      on the presence of at least three of four of the following symptoms: spontaneous
      epistaxis, cutaneous telangiectases, arteriovenous malformations in internal
      organs and familiarity. Recurrent complications are severe anaemia, stroke,
      portal and pulmonary hypertension. The peculiar characteristic of this disease is
      the diffusion of arteriovenous malformations, that is, localised abnormal
      arteriovenous connections affecting both microvasculature and large vessels. HHT
      is actually a heterogenous genetic disorder, divided into two clinically
      indistinguishable forms: HHT1 caused by mutations in endoglin gene mapping on
      chromosome 9q, and HHT2 caused by mutations in ALK1 located on chromosome 12q.
      Haploinsufficiency is the underlying mechanism for endoglin and most ALK1
      mutations. Such mutations lead to a deficiency in angiogenesis, i.e. the
      sprouting of new vessels from pre-existing ones. To date, little is still known
      about the mechanism(s) responsible for lesion formation, development and slow
      growth. Current models focus on the role that TGF-beta superfamily members, a
      vast group of multifunctional cytokines, play in endothelial responses to
      angiogenic stimuli. As both genes seem to act in TGF-beta signal transduction
      pathways, SMAD proteins are also thought to be involved. There is no clear
      explanation accounting for the strong variability shown even among members of the
      same family despite the sharing of the same disease-causing mutation, and why
      lesions are spatially discrete.

PMID- 16611100
TI  - Involvement of the transforming growth factor beta in the pathogenesis of
      hereditary hemorrhagic telangiectasia.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is characterized by vessel
      alterations such as dilatation of postcapillary venules and arterio-venous
      communications, which account for the major clinical manifestations of the
      disease. Two types of HHT have been characterized HHT-1 and HHT-2, respectively,
      depending the former on endoglin mutations and the latter on activin receptor
      like kinase 1 (ALK-1) mutations. Both endoglin and ALK-1 bind to the transforming
      growth factor (TGF) superfamily which, physiologically, regulates the activities
      of endothelial cells and also those related to the extracellular matrix. In this
      review, the salient features of TGF-beta will be outlined with special reference
      to its activity on the immune system and on tumorigenesis. Furthermore, the
      involvement of TGF-beta in the pathogenesis of some gastrointestinal diseases
      will be discussed and, in particular, in the course of liver disease,
      Helicobacter pylori infection and inflammatory bowel disease. In the light of
      these data and of animal model of HHT, the potential risk of developing other
      diseases in HHT patients will be discussed.

PMID- 16611101
TI  - Ablation of T-helper 1 cell derived cytokines and of monocyte-derived tumor
      necrosis factor-alpha in hereditary hemorrhagic telangiectasia: immunological
      consequences and clinical considerations.
AB  - Experimental evidences on the adaptive immune response in patients with
      hereditary hemorragic telagiectasia (HHT) are lacking. Here, we report in 9
      patients with HHT a multiple deficit involving the intracellular expression of T
      helper (h)1-derived cytokines [Interferon (IFN)-gamma, Interleukin (IL)-2 and
      Tumor Necrosis Factor (TNF)-alpha] and of monocyte-derived TNF-alpha. On the
      other hand, percentages of Th2-derived cytokines (IL-4, IL-5 and IL-10) were
      normal or, in some cases, above normality. Quite interestingly, monocyte-derived
      IL-10 was detectable in 5 out of 9 patients in a percentage of cells comparable
      to controls or exceeding normal levels. Taken together, these data point out, in
      HHT, an ablation of Th1-responses, while Th2-type cytokines are preserved, thus
      exerting either a suppressive effect on Th1-cells (via IL-4 and IL-10) or an
      antiinflammatory response on monocyte-derived TNF-alpha (via IL-10). Furthermore,
      monocyte-derived IL-10 may also contribute to the antiinflammatory activity seen
      in HHT. According to current literature even if patients with HHT do not exhibit
      certain diseases, such as autoimmune diseases, cancer and abnormal responses to
      pathogens, the observed immune deficits need to be diagnosed and therapeutically
      corrected.

PMID- 16611102
TI  - Patients with Hereditary Hemorrhagic Telangectasia (HHT) exhibit a deficit of
      polymorphonuclear cell and monocyte oxidative burst and phagocytosis: a possible
      correlation with altered adaptive immune responsiveness in HHT.
AB  - Hereditary Hemorrhagic Telangiectasia (HHT) is a rare genetic disease
      characterized by mutations occurring in the endoglin and ALK-1, two receptors of
      transforming growth factor-beta1. From a pathogenic point of view, a possible
      involvement of the immune system in HHT has been suggested since a mononuclear
      cell infiltrate was found around the area of telangiectases. Up until now, no
      information has been available about the role played by leukocytes in HHT and the
      mechanisms elicited by secretion of their mediators. However, the fact that a
      deficit of adaptive immunity in HHT has been reported in a companion paper in
      this issue will represent a great contribution to the understanding of HHT
      pathogenesis. The purpose of this study was to evaluate whether patients with HHT
      manifest also alterations in the innate immune response. Therefore, the phenotype
      of T, B and natural killer lymphocytes, serum immunoglobulin levels, phagocytosis
      and oxidative burst activity exerted by polymorphonuclear cells (PMN) and
      monocytes (MO) were analyzed in 22 patients. Twenty individuals demonstrated
      single or multiple deficits of PMN and MO functions, while the immunophenotype of
      lymphocytes and serum concentrations of immunoglobulins were normal. To the best
      of our knowledge, this is the first demonstration of a reduction in PMN and MO
      functions in HHT, thus suggesting a higher susceptibility to infectious
      complications in these patients. The relationship between innate immune deficits
      and T helper 1 and monocyte-derived cytokine dysfunction in HHT, as previously
      reported, is discussed.

PMID- 16611103
TI  - HHT: a rare disease with a broad spectrum of clinical aspects.
AB  - HHT is an autosomal dominant disease characterised by diffuse muco-cutaneous and
      visceral telangiectases in potentially all organs. Mutations in two different
      genes identify HHT type 1 and HHT type 2: endoglin located on chromosome 9q33-q34
      and ALK-1 or ACVRL1 on chromosome 12q13, respectively. The existence of a third
      locus has also been hypothesised. HHT-1 is considered a more severe form of the
      disease with an earlier onset of epistaxis and telangiectases and a higher
      prevalence of pulmonary arteriovenous malformations than that found in HHT-2
      subjects. Usually, a typical HHT patient has epistaxis, muco-cutaneous
      telangiectases and GI bleeding in later life, even though this clinical scenario
      represents only one of the possible HHT patterns. In fact, vascular malformations
      often remain silent until the onset of a severe complication, which frequently is
      the first clinical manifestation of HHT. The lung and brain are of particular
      concern because each may contain clinically silent lesions that can result in
      sudden morbidity and mortality. At present, awaiting the availability of genetic
      testing, only an expert in the clinical patterns and diagnostic imaging of HHT
      can permit a definite diagnosis in individuals at high risk for the disease.

PMID- 16611104
TI  - HHT in childhood: screening for special patients.
AB  - Hereditary hemorrhagic telangiectasia (HHT) or the Rendu-Osler-Weber disease is a
      systemic fibrovascular autosomal dominant dysplasia, recognised when three of the
      following four clinical manifestations are present, according to the proposal of
      Shovlin.: recurrent nosebleeds, lelangiectasias of the skin, visceral lesions,
      and positive family history. HHT is often difficult to diagnose on the basis of
      history and physical examination alone, especially in infants and children. The
      signs and symptoms of HHT are nonspecific and are extremely variable within
      families. Given the frequent occurrence of clinically silent lesions in lung and
      brain arteriovenous malformations which can result in morbidity or death, much
      consideration should be given to screening patients with HHT for asymptomatic
      fistulae and to their treating once they are discovered. Presymptomatic
      interventions in such cases may substantially affect the outcome. It may be
      possible to state that lesions of HHT arise early in life, but do not reach
      sufficient size to cause symptoms until the second decade. Furthermore, as
      clinical manifestations often occur later in life, the development and the
      implementation of a molecular diagnosis will allow the identification of subjects
      with no evident signs of the disease but carrying the familial mutation. This is
      fundamental in order to establish reliable screening protocols for the prevention
      and cure of the disease and, to determine the presence of family members with no
      disease-associated mutation, who do not require further clinical screening.

PMID- 16611105
TI  - Hereditary haemorrhagic teleangiectasia: diagnostic imaging of visceral
      involvement.
AB  - Hereditary Haemorrhagic Telangiectasia (HHT), also known as Rendu-Osler-Weber
      disease, is an autosomal-dominant vascular disease characterised by mucocutaneous
      or visceral angiodysplastic lesions (telangiectases and arteriovenous
      malformations), which may be widely distributed throughout the cardiovascular
      system. Its diagnosis is based on clinical criteria. Liver, lungs and brain, in
      order of prevalence, are the most frequently involved visceral districts of the
      body other than skin and nasal mucosa. Liver involvement is frequent and
      characterised by the presence of intrahepatic shunts, disseminated
      intraparenchymal telangiectases and other vascular lesions. Although it is
      usually asymptomatic, congestive cardiac failure, portal hypertension,
      portosystemic encephalopathy, cholangitis or atypical cirrhosis are possible
      complications. Pulmonary arteriovenous malformations involve more than one third
      of HHT patients and can consist of diffuse telangiectases or high-flow low
      pressure shunts between pulmonary arteries and veins. Pulmonary involvement can
      cause serious complications: hypoxaemia, pulmonary or pleural hemorrhage,
      paradoxical embolism into cerebral circulation. Various types of cerebrovascular
      malformations can affect HHT patients and the most common are arteriovenous
      malformations, consisting of one or more feeding arteries connected to one or
      more draining veins. Diagnostic imaging has a fundamental role in detecting the
      alterations involving these various districts in the body. The possibility to
      perform fast and complete studies and to provide high quality multiplanar and
      angiographic reconstructions, gives multi-detector row helical computed
      tomography and magnetic resonance the ability to detect and characterise the
      complex anatomo-pathological alterations typical of HHT. Ultrasonography seems to
      be the best screening modality for hepatic and pulmonary involvement.

PMID- 16611106
TI  - Endovascular treatment of pulmonary and cerebral arteriovenous malformations in
      patients affected by hereditary haemorrhagic teleangiectasia.
AB  - Hereditary Haemorrhagic Teleangiectasia (HHT) is a vascular disorder of
      angiogenesis transmitted in an autosomal dominant pattern, characterised by
      heterogeneity in clinical manifestations. One of the most important organ
      involved is lung, including pulmonary arteriovenous malformations (PAVM). PAVM
      occur in 20 to 30% of the HHT population and recently are considered a marker of
      disease. PAVM are direct artery-to-vein connections with low pressure and without
      an interveining capillary bed. PAVM are classified as simple (supplied by one
      feeding artery) or complex (receiving blood supply from two or more feeding
      artery). According to the international reports, treatment it's recommendable for
      all PAVM with feeding vessels 3mm or larger, in order to reduce the risk of
      cerebral ischaemia and neurologic manifestations frequently attributed to
      paradoxical embolisation. Transcatheter embolotherapy of PAVM is a form of
      treatment based on occlusion of the feeding artery to a PAVM by using platinum
      coils or detachable balloons. The technique of coil embolisation involves the
      exact localisation of PAVM by pulmonary angiography followed by superselective
      percutaneous caheterisation of feeding artery obtained by using a dedicated 7F
      guiding catheter, which coaxially allocates a 5F hydrophilic catheter advanced in
      order to perform both superselective angiography of feeding artery and
      embolisation itself. Inside the 5F catheter the platinum coils are advanced using
      a .035'' guide-wire and released until an optimal occlusion of feeding artery is
      achieved. At the end of the procedure angiographic control is performed in order
      to verify the occlusion of feeding artery. The use of platinum coils is
      preferable over detachable balloons when feeding artery are greater than 7 mm in
      diameter and have irregular anatomical configuration. On the other hand, the
      principal advantage of using detachable balloons is that the balloon itself can
      be deflated and repositioned if necessary. Transcatheter embolotherapy is
      technically safe and clinically effective and may represent the primary choice of
      treatment in HHT patients. On the other hand the most common complications of
      this treatment (pleurisy and air embolism) can be prevented by using some tips
      during the embolisation procedure like "anchor technique," "scaffold technique"
      and "balloon assisted technique." Cerebral arteriovenous malformations (CAVM) are
      present in 10-20% of patients with HHT and multiple in 50% of cases. Cortical
      surface is the most frequent localisation. Angiography is needed to diagnose all
      CAVM and to clarify the angioarchitecture of the lesion. In HHT CAVM are usually
      either micro-AVM, with a nidus not bigger than 1 cm, or small AVM, with a nidus
      between 1 and 3 cm. Quite frequently there are lesions characterised by
      arteriovenous fistulas. In the three patterns of CAVM usually found in HHT, small
      AVM are the most risky for bleeding although the risk is lower than that
      associated with sporadic ones. It is estimated from 0.38 to 0.69% per year in
      spite of the general incidence of bleeding in sporadic CAVM that ranges from 2 to
      4% per year. In HHT patients, at present, the precise indications and timing of
      treatment are not established. Trend is to treat small AVM and AVF and to follow
      up micro-AVM with MRI and angiography. As for sporadic CAVM, treatment of small
      AVM is usually referred to stereotactic radiosurgery. Endovascular embolisation
      is proposable if the lesion is easily reachable by microcatheterism and the
      position of the microcatheter is safe. Glue is used for embolisation and the
      technique is briefly discussed.

PMID- 16611107
TI  - The need for an interdisciplinary network of investigations on HHT.
AB  - In the last years, the understanding of HHT has greatly progressed. The two genes
      for most on cromosomes 9 and 12 have been discovered and the existence of a third
      involved gene has been predicted. Recent progress in the field of genetics has
      allowed the identification of many gene mutation thus facilitating the
      characterisation of the at risk members of the same family. Complications from
      bleeding or shunting (pulmonary AVMs) may be sudden and life-threatening
      (hemothorax, haemoptysis, stroke and brain abscess). Catastrophic events are
      preventable by early diagnosis and treatment. Appropriate screening programmes
      are mandatory and multi-specialistic cooperation is needed. Special centers have
      been developed in the world, where physicians, who are specialised and trained in
      all aspects of HHT, are working to develop better therapeutic approaches for the
      disease and to locate new genes in view of the future potential of gene therapy
      for this condition.

PMID- 16611109
TI  - Biology and pharmacology of the platelet P2Y12 receptor.
AB  - Platelets possess two receptors for ADP, P2Y(1) and P2Y(12). ADP is released from
      platelet dense granules upon platelet activation by numerous agonists and thereby
      amplifies platelet responses regardless of the initial stimulus. The P2Y(1)
      receptor is one of many platelet receptors coupled to Gq and initiates ADP
      induced activation. The P2Y(12) receptor on the other hand is linked to Gi and
      plays a special role in the amplification of platelet activation initiated by
      numerous other pathways. Platelet activation leads to a range of responses that
      play a critical role in arterial thrombosis and the inflammatory responses
      associated with this, including platelet aggregation, dense and alpha granule
      secretion and procoagulant activity. P2Y(12) receptor activation yields powerful
      amplification of these processes such that P2Y(12) receptor antagonists may have
      dramatic inhibitory effects on platelet function regardless of the activating
      stimuli. This phenomenon, coupled with the restricted distribution of the P2Y(12)
      receptor in humans, makes the receptor an ideal target for pharmaceutical
      therapy. This has already been established by the therapeutic success of
      clopidogrel, which acts, via an active metabolite, on this receptor. However,
      current therapeutic regimens of clopidogrel yield variable and incomplete P2Y(12)
      receptor blockade and more effective strategies to block P2Y(12) receptor
      activation offer the potential of greater clinical efficacy.

PMID- 16611110
TI  - Clopidogrel resistance: implications for coronary stenting.
AB  - Clopidogrel, in combination wih aspirin, is currently the drug of choice to
      prevent thrombosis after coronary stent implantation. Currently, clopidogrel is
      administered to the vast majority of patients without any assessment of platelet
      inhibition. Response variability and resistance, however, definitely occur to
      clopidogrel treatment. Preliminary data support the hypothesis that patients with
      reactive or clopidogrel nonresponsive platelets are at risk for thrombotic
      events. However, the magnitude of the clinical effect remains unknown and
      relationship between nonresponsiveness and risk of clinical events is under
      investigated. Several important questions that must be answered are: A) What is
      the relation of clopidogrel resistance and high platelet reactivity to the
      occurrence of stent thrombosis, recurrent myocardial infarction, stroke and
      death?; B) Is there a threshold of platelet reactivity that correlates with the
      onset of thrombotic risk?; and C) What is the cost of administering clopidogrel
      to non-responsive patients? Finally, our understanding of the clinical relevance
      of drug resistance and high platelet reactivity should be facilitated by the use
      of validated point-of-service devices. The mechanisms of the response variability
      to clopidogrel remain incompletely defined. The contribution of intra- and
      extracellular pathways are under investigation.

PMID- 16611111
TI  - Thienopyridines and statins: assessing a potential drug-drug interaction.
AB  - Clopidogrel and statins are frequently administered in patients with ischemic
      heart disease or other atherothrombotic manifestations and are effective in the
      prevention of cardiovascular disease. The thienopyridine clopidogrel is a pro
      drug metabolised in the liver via the cytochrome P450 (CYP) 3A4 system to the
      active compound which inhibits the P2Y(12) ADP platelet receptor. The assumption
      exists that the effect of clopidogrel in inhibiting platelet aggregation is
      attenuated by co-administration of lipophilic statins such as atorvastatin or
      simvastatin which are metabolised by the CYP3A4 system to inactive substrates.
      Assessing a possible drug-drug interaction ex-vivo, inconclusive studies have
      been published: In an aggregometer study, a strong and dose-dependent
      interference between atorvastatin and the inhibitory effect of clopidogrel on
      platelet function was observed. Another study, measuring the effect of
      clopidogrel by flow cytometry, found a significant attenuation of the clopidogrel
      effect by lipophilic statins, predominantly in the loading phase. In contrast a
      recent study, which used 600 mg clopidogrel for loading, found no significant
      interference between various statins and clopidogrel on ADP-induced platelet
      aggregation and in addition another study revealed no attenuation of the
      clopidogrel effect despite statin co-medication after 5 weeks. Additionally,
      retrospective analysis of clinical studies (CREDO-study) or registries (MITRA
      PLUS) revealed no significant influence of different statins on the clinical
      outcome in patients treated with clopidogrel. However, these clinical studies
      showed a trend towards a diminishing effect of clopidogrel on those treated with
      cytochrome CYP3A4 metabolised statins. Even more important seems to be the
      considerable variability in the response of the antiplatelet effect of
      clopidogrel. A certain percentage of patients apparently do not respond
      adequately to clopidogrel treatment. This effect of clopidogrel resistance seems
      to be more important as the potential interference between CYP3A4 metabolized
      statins and clopidogrel. Finally, up until now sufficient evidence has not been
      gained to prefer hydrophil statins on patients receiving clopidogrel co
      medication or when to discontinue the use of statins in clopidogrel treatment.
      Prospective studies are necessary in order to evaluate the magnitude of
      clopidogrel resistance and the impact of clopidogrel co-medication as well as to
      redefine antithrombotic therapy for this subgroup.

PMID- 16611112
TI  - Thienopyridines in percutaneous coronary interventions: standard procedures and
      high risk subsets.
AB  - Due to the significant clinical and economic consequences of subacute stent
      thrombosis and the use of more complex devices (brachytherapy, drug eluting
      stents) in a variety of clinical situations (i.e. acute coronary syndromes),
      initiation and duration of a combined antiplatelet therapy using aspirin and a
      thienopyridine drug has become an issue of ongoing discussion in interventional
      cardiology. This review will provide a short introduction into the
      pathophysiology of stent thrombosis before standard procedures and critical
      issues on the use of thienopyridines in the setting of coronary interventions are
      discussed. Furthermore, clinically relevant issues that are not clearly covered
      by recommendations or guidelines like thienopyridines after coronary
      interventions in patients on chronic oral anticoagulation are also addressed.

PMID- 16611113
TI  - The role of antiplatelet agents in the management of patients receiving
      intracardiac closure devices.
AB  - Transcatheter closure of septal defects has become a widely used alternative to
      surgery or life-long anticoagulant therapy especially in patients with atrial
      septal defects (ASD) and patent foramen ovale (PFO). Post-procedural
      complications include thrombus formation on the occluder in about 0-10% of all
      cases. Therefore antithrombotic prophylaxis after device implantation is believed
      to be necessary, but still is variable and remains controversial. To date no
      randomized studies have been published to assess the optimal anticoagulation
      strategy. Thus, therapy is based on empirical data, local experience and case
      reports from the literature. The present review tries to give an overview on most
      of these mainly retrospective single center studies and summarizes their results.
      Factors influencing the rate of thrombus formation may be device type, existence
      of thrombophilic disorders and prophylactic medication. Thrombus formation has
      been described for each of the existing occluder types without a significant
      difference between the devices. For antithrombotic prophylaxis, most centers at
      present use either acetyl salicylic acid alone (ASA; 81 to 325 mg) for 6 months
      or a combination of ASA and clopidogrel (75 mg) for 6 to 8 weeks followed by ASA
      for additional 4 to 8 months. Inherited thrombophilic disorders should be
      excluded before device implantation in order to adapt antithrombotic prophylaxis.
      Follow-up examinations after device implantation should be performed using TEE
      within the first 4 weeks after implantation. Thus, thrombi may be recognized
      early enough to extend the antithrombotic regimen in order to avoid surgical
      device explantation.

PMID- 16611114
TI  - Primary and secondary stroke prevention with antiplatelet drugs.
AB  - Aspirin is not effective in the primary prevention of stroke. Patients with TIA
      or ischemic stroke carry a risk of recurrent stroke between 5 and 20% per year.
      In patients with TIA or ischemic stroke of noncardiac origin antiplatelet drugs
      are able to decrease the risk of stroke by 11-15% and the risk of stroke, MI and
      vascular death by 15-22%. Aspirin is the most widely used drug. It is affordable
      and effective. Low doses of 50-325 mg aspirin are as effective as high doses and
      cause less gastrointestinal side effects. Severe bleeding complications are dose
      dependent. The combination of aspirin with slow release dipyridamole is superior
      to aspirin alone for stroke prevention. Clopidgrel is superior to aspirin in
      patients at high risk of recurrence. The combination of aspirin plus clopidogrel
      is not more effective than clopidogrel alone but carries a higher bleeding risk.
      None of the antiplatelet agents is able to reduce mortality.

PMID- 16611115
TI  - Treatment of recurrent epistaxis in HHT.
AB  - No optimal treatment modality is currently available for the treatment of
      recurrent epistaxis in HHT. In this review, different therapeutic concepts are
      discussed together with their pathophysiologic background. Patients often profess
      a preventive effect for nasal ointments and use packings which can be self
      administered in the case of bleeding. An effective first-line treatment for
      physicians is the endonasal laser coagulation or argon plasma coagulation. A
      second line surgical procedure is septodermoplasty according to Saunders which
      can provide long-lasting relief if performed correctly. There have been reports
      on antifibrinolytic agents and hormones, but their efficacy has yet to be
      determined.

PMID- 16611117
TI  - Antiviral drug discovery targeting to viral proteases.
AB  - Proteases fulfill multiple roles in health and disease, and considerable interest
      has been expressed in the design and development of synthetic inhibitors of
      disease-related proteases. Virus-encoded proteases have been shown to be involved
      in the replication of many viruses. The success of anti-HIV-1 therapy using
      specific and potent protease inhibitors suggests that viral proteases can be the
      valid molecular targets for the development of antiviral drugs against other
      viruses. Intensive genetic and biochemical studies have been conducted on viral
      proteases and new insights and results are rapidly emerging. This work reviews
      features of viral proteases with respective to the development of effective
      antiviral therapy.

PMID- 16611119
TI  - Antiviral therapy targeting viral polymerase.
AB  - Viral DNA and RNA polymerases are enzymes, which are responsible for copying the
      genetic materials of viruses and are therefore central components in the life
      cycles of viruses. The polymerases are essentially required for the replication
      of viruses. The reverse transcriptase (RT) of the retroviruses and the
      hepadnaviruses is the sole viral enzyme required for the synthesis of DNA from
      viral RNA. Viral polymerases are therefore an extremely favorable target for the
      development of antiviral therapy. The success of anti-HIV-1 therapy using
      inhibitors specifically targeting HIV RT suggests that other viral polymerases
      can be the valid molecular targets for the design of antiviral drugs. Intensive
      structural and functional studies of viral polymerases have been conducted and
      have opened new avenues for the development of more effective antiviral therapy.
      This review summarizes the insights gained from recent structural and functional
      studies of antiviral agents, which target viral polymerases. The primary focus
      will be on hepatitis C virus (HCV), herpesviruses, HIV, hepatitis B virus (HBV)
      and influenza virus.

PMID- 16611120
TI  - Herpes simplex viruses in antiviral drug discovery.
AB  - Since the 1950's, herpes simplex viruses (HSV) have played prominent roles in the
      development of antivirals. The first efficacious antivirals, as well as the first
      safe for systemic use, were developed against HSV. It was only in 1995 when the
      first antiviral against a target not validated first with HSV was approved for
      clinical use (sequinavir). The early successes of targeting HSV DNA replication
      were most influential in developing the concept that antiviral drugs must target
      viral proteins. Such concept has ensured the safety of current antiviral drugs,
      which all target viral proteins. Current antivirals have proven to have no major
      negative effects on non-infected cells or treated patients. Because of their
      success widespread and use, however, these drugs have been found to have some
      limitations. Perhaps the clinically most important one is their ability to
      promptly select for drug-resistant viral strains. Owing to such limitations,
      cellular proteins are now considered as valid targets for novel antiviral drugs.
      The discovery that pharmacological CDK inhibitors (PCIs) inhibit HSV replication
      through novel mechanisms played a major role in this new appreciation of cellular
      proteins as potential targets for antivirals. This appreciation is reflected in
      the scheduling of PCIs to enter clinical trials as antivirals (against HIV).
      Herein, we will review the roles of HSV as model viruses in the discovery and
      development of antiviral drugs. The major focus will be on the recent discovery
      on the activities of PCIs against HSV and other viruses.

PMID- 16611121
TI  - Recent advances in antiviral agents: antiviral drug discovery for hepatitis
      viruses.
AB  - Hepatitis B virus (HBV)- or hepatitis C virus (HCV)- associated liver diseases
      are now one of the important health problems in the world because of the high
      numbers of patients and the serious consequences. Recently, however, relatively
      effective treatments with antiviral agents have become available. Interferon
      (IFN), lamivudine and adefovir are now approved for treatment of HBV-associated
      liver diseases and they have been shown to be fairly effective. The goal of
      treatments for HBV-associated liver disease is to achieve a clinical cure in as
      short a period as possible without producing resistance mutation of the virus.
      Several nucleotide analogues with more potent antiviral activities are now in
      clinical trials. In the case of HCV-associated liver diseases, Pegylated IFN (Peg
      IFN) + ribavirin combination therapy is the standard and most effective treatment
      with a sustained response of 60-70%. The goal of the treatments for these liver
      diseases is to induce the complete eradication of the infected virus and at
      present new anti HCV drugs targeting the molecular segments of the virus are
      under development. It is expected that the complete eradication of infected virus
      will be possible in most cases in the near future.

PMID- 16611122
TI  - Current status of anti-picornavirus therapies.
AB  - Picornaviruses are important human pathogens causing severe morbidity and some
      mortality with the potential to cause worldwide crippling disease. Currently,
      there are few treatments for many of the viruses in the Picornaviridae, For
      rhinoviruses, there are no approved treatments, although ruprintrivir looks
      promising in clinical trials and pyridazinyl oxime ethers may prove useful.
      Poliovirus treatments are needed to supplement the World Health Organization's
      polio eradication plan in order to treat infections caused by reversion of the
      attenuated vaccine virus and to supplement vaccine coverage control in polio
      endemic areas. However, no promising compounds for treatment of poliovirus have
      been developed due to the efficacy of the vaccines in use. Broad-spectrum
      inhibitors developed for other picornavirus may be useful for poliovirus
      infections. Coxsackievirus infections in children and in infants are being
      treated with pleconaril with some efficacy in reducing mortality and improving
      recovery, albeit the treatment is often on a compassionate use basis. There are
      no therapies for echovirus infections. Very little drug discovery research is
      being done to develop inhibitors for echovirus infections, probably due to the
      broad-spectrum inhibition exhibited by capsid binding agents and protease
      inhibitors discovered for treatment of other picornaviruses. For example,
      pyridazinyl oxime ethers are inhibitory to most echoviruses. Treatments for
      enterovirus infections are also limited, although in a small clinical trial,
      milrinone seemed to reduce mortality and improve recovery from EV71-induced
      pulmonary edema. Thus, these results strongly emphasize the need for the
      development of potent and nontoxic compounds for the treatment of picornavirus
      infections.

PMID- 16611118
TI  - Understanding helicases as a means of virus control.
AB  - Helicases are promising antiviral drug targets because their enzymatic activities
      are essential for viral genome replication, transcription, and translation.
      Numerous potent inhibitors of helicases encoded by herpes simplex virus, severe
      acute respiratory syndrome coronavirus, hepatitis C virus, Japanese encephalitis
      virus, West Nile virus, and human papillomavirus have been recently reported in
      the scientific literature. Some inhibitors have also been shown to decrease viral
      replication in cell culture and animal models. This review discusses recent
      progress in understanding the structure and function of viral helicases to help
      clarify how these potential antiviral compounds function and to facilitate the
      design of better inhibitors. The above helicases and all related viral proteins
      are classified here based on their evolutionary and functional similarities, and
      the key mechanistic features of each group are noted. All helicases share a
      common motor function fueled by ATP hydrolysis, but differ in exactly how the
      motor moves the protein and its cargo on a nucleic acid chain. The helicase
      inhibitors discussed here influence rates of helicase-catalyzed DNA (or RNA)
      unwinding by preventing ATP hydrolysis, nucleic acid binding, nucleic acid
      release, or by disrupting the interaction of a helicase with a required cofactor.

PMID- 16611123
TI  - New strategies for immune-mediated anti-viral drug and vaccine development.
AB  - Substantial progress in the development of new anti-viral drugs has taken place
      in recent years. Most of these new drugs belong to three groups of compounds,
      nucleoside analogs, thymidine kinase-dependent nucleotide analogs and specific
      viral enzyme inhibitors. Although these drugs revolutionized the treatment of
      several viral diseases, the involvement of the immune system is crucial for
      complete recovery and prevention of re-infection. New advances in the
      understanding of immune regulation mechanisms, mainly the role of cytokines, led
      to the development of several new immunologically-based anti-viral drugs and
      treatments. The most studied group of immunomodulators is the cytokines, some of
      which were shown to act as potent stimulators of immune responses. Other, non
      cytokine immune modulators have also been successfully employed in both humans
      and experimental animals as anti-viral drugs of which several are currently in
      clinical trials. Advances in genetic engineering and transgenic mouse
      technologies facilitated the production of humanized as well as authentic human
      anti-viral monoclonal antibodies. Some of these antibodies proved to be
      clinically efficacious and are commercially produced as anti-viral drugs. As is
      often the case in anti-viral treatments, a combination of conventional and an
      immune-mediated anti-viral drugs or a combination therapy involving
      immunomodulators, therapeutic vaccines, immune intervention and even gene therapy
      might prove most efficacious as a treatment for a particular virus. Most of the
      advances made in anti-viral treatments have also been applied to the development
      of new vaccines. Some of the classical attenuated viruses are being replaced by
      recombinant attenuated viruses. Recombinant viral vaccines containing genes
      encoding other viral antigens and/or cytokines are being tested as new vaccines.
      Several chimeric viral vaccines have proven efficacious in experimental animals
      and are now in different phases of clinical trials. This review will encompass
      the major new developments in this field, including some that have not yet been
      subjected to human trials.

PMID- 16611124
TI  - Soft condensed matter in pharmaceutical design.
AB  - In recent years pharmaceutical design has been facing the needs expressed by new
      therapeutic methodologies such as gene therapy, targeted delivery and closely
      related diagnostic fields as contrast enhancing agents for ultrasonic
      investigations. In this context pharmaceutical research has diversified the
      efforts toward a more integrated approach where the efficacy of an active
      molecule is enhanced and assisted by the surrounding carrier. Usually this drug
      platform is a hydrogel matrix, a multicomponent system constituted by an aqueous
      solution and a polymeric moiety imparting different functions to the matrix, as
      responsiveness to external stimuli, affinity to receptors, controlled drug
      release. Such devices represent one of the leading topics of the soft condensed
      matter recent research, a domain where physics, chemistry and bioengineering
      cross each other with the aim to achieve an integrated description of these
      materials. In this respect modern drug design will make use more and more of
      concepts proper of soft condensed polymer and colloidal sciences. In this review
      we will describe the state-of-art in the field of the matrices used in innovative
      drug formulations with a particular emphasis on the implications to
      pharmaceutical design along with the experimental and theoretical investigation
      tools worked out in the last decade.

PMID- 16611125
TI  - Porcine cytochrome P450 and metabolism.
AB  - The pig and especially the minipig are becoming increasingly used as a test
      animal both in pharmacological and toxicological testing of new compounds. The
      minipig is used because of its size, it is easy to handle and less test substrate
      is required. When using an animal species for testing it is of importance to know
      if the test animal's posses the same abilities to metabolize drugs as humans.
      Some of the P450 enzymes have been characterized in the pig regarding substrate
      specificity, inhibition and regulation. The porcine enzymes CYP1A, CYP2A and
      CYP3A all metabolize the same test substrates as the human enzymes, whereas the
      enzymes CYP2B, CYP2D, and CYP2E in pig on the other hand seem to be different
      from the human enzymes concerning metabolism of the well know test substrates.
      Some of the porcine enzymes have been sequenced i.e. CYP1A, CYP2A, CYP2B, CYP2D,
      CYP2E and CYP3A and not surprisingly the porcine CYPs that metabolize the human
      test substrates are about 75% identical in cDNA sequences. What is needed is
      inhibitory antibodies against each of the porcine enzymes, in order to test
      whether a test compound is metabolized by one or the other enzyme. Until now
      chemical inhibitors have been used, but they are rarely 100% specific. Anti-human
      inhibitory antibodies have also been used, but they may not recognize the porcine
      enzyme and therefore will not inhibit the reaction. Antibodies for immunoblotting
      would also make it possible to estimate how much of the total P450 the individual
      enzymes comprise. From what is known about the porcine P450, it can be concluded
      that the pig seems to be a good test species if CYP1A, CYP2A or CYP3A are
      involved in the metabolism of the test compound, depending on the contribution of
      other enzymes in competing pathways.

PMID- 16611127
TI  - The relationship between cleft lip, maxillary hypoplasia, hypoxia and phenytoin.
AB  - Cleft lip (CL) is a common malformation that has both genetic and exogenous
      causes. The main pharmaceutical cause is exposure to phenytoin during early
      facial development in the 5th to 6th weeks of gestation. Phenytoin also causes CL
      if administered to pregnant rats during the period of early facial development.
      Evidence is presented that in the pregnant rat, a teratogenic dose of phenytoin
      slows the early embryonic heart and causes a prolonged period of embryonic
      hypoxia. It is proposed that this hypoxia, through an undefined downstream
      mechanism, leads to the development of CL. The involvement of hypoxia in the
      pathogenesis of CL is in agreement with studies in mouse strains with a
      spontaneous rate of CL in which exposure to hypoxia has been shown to increase
      the rate and hyperoxia to decrease the rate. Other exogenous risk factors during
      pregnancy for human CL include maternal cigarette smoking, residence at high
      altitude and exposure to corticosteroids. It is suggested that these exposures
      all involve an increased risk of embryonic hypoxia. It has been proposed that
      phenytoin affects the embryonic heart by inhibition of the human-ether-a-go-go
      (HERG) potassium channel. Phenytoin also inhibits sodium and calcium channels and
      these properties may also be involved in the observed effect on the embryonic
      heart. Phenytoin-induced bradycardia leading to embryonic hypoxia may be an
      important mechanism by which phenytoin causes birth defects.

PMID- 16611128
TI  - History and evolution of reproductive and developmental toxicology guidelines.
AB  - Birth defects and other adverse outcomes of pregnancy have been known since
      before the industrial age, but the need for guidelines to test chemicals to which
      pregnant women might be exposed was defined by the thalidomide tragedy in the
      1950s and early 1960s. During the five decades that followed the tragedy,
      guidelines were written to test drugs, foods, and environmental contaminants. The
      guidelines were written to fulfill national needs, and then were expanded to
      international levels in order to streamline procedures in the expanding global
      economy. Multiple sets of animal guidelines were written, based on the need to
      simulate human experience. It was soon realized that the underlying principles
      were similar for all guidelines. Guidelines gradually evolved in two directions,
      in complexity and number of endpoints measured and in the expansion of
      internationally acceptable guidelines. This manuscript reviews, in chronological
      order, some of the milestones in the development of guidelines for animal studies
      and in the interpretations for safety assessment. Guidelines for long-term and
      short-term studies are reviewed, followed by a discussion of recently added
      endpoints and the future integration process for the assessment of reproductive
      toxicity risk.

PMID- 16611129
TI  - Whole embryo culture: an important tool in developmental toxicology today.
AB  - The number of candidate chemicals or drugs for registration and authorization is
      increasing at a fast rate and only few of the existing substances have been
      tested for teratogenicity to date. Therefore, there is high pressure on
      authorities to accept models like the whole embryo culture as a screening system
      for safety evaluation procedures. In view of this background the gradual
      development of the whole embryo culture into a standardized, scientifically
      validated tool for developmental toxicology during the last 70 years is
      summarized. The methodological development of the culture technique is described
      with the completion, improvement and refinement of the basic culture method as
      main intention. Special attention was paid to different culture techniques,
      culture media, gassing schedules, and evaluation strategies. Furthermore the
      importance of taking "in vitro pharmacokinetics" into consideration when a
      comparison of in vitro/in vivo results from embryotoxicity testing is intended,
      is stressed. Additionally, the demonstration of the broad spectrum of useful
      scientific applications when using this culture system in combination with
      sophisticated analytical techniques is demonstrated. Finally, an overview on
      different strategies for the validation of this culture system as an in vitro
      embryo toxicity test is provided and the officially accepted formal validation
      process for this application is summarized. The successful validation makes the
      whole embryo culture a complex in vitro embryotoxicity test with high accuracy
      and predictability. This robust in vitro system modelling the main phase of
      rodent organogenesis with a high reproducibility is valuable enough to attract
      special attention in related scientific fields.

PMID- 16611130
TI  - Mechanisms and risk of chemically induced aneuploidy in mammalian germ cells.
AB  - Aneuploidy is a pathological condition that affects 35% of human spontaneous
      abortions and 0.3% of livebirths. In spite of the increasing knowledge about
      molecular mechanisms of meiosis and chromosome segregation, maternal age remains
      the only ascertained aetiological factor. Genetically modified mouse models have
      been produced that show increased incidence of aneuploid gametes or abnormalities
      in meiotic recombination and synapsis. They suggest that genetic polymorphisms
      might also be involved in the aetiology of human germ cell aneuploidy.
      Experimental studies in the mouse have identified chemicals that can induce
      aneuploidy in male and female germ cells. Compounds affecting spindle
      assembly/dynamics are potent aneugens for oocytes and less so also for
      spermatocytes. They are active at acute doses during a short time interval
      preceding the metaphase-to-anaphase transition. Topoisomerase inhibitors are also
      meiotic aneugens which act on the recombination process; for the first time, the
      production of viable aneuploid mouse progeny was shown after paternal treatment
      with etoposide. A comparison between in vitro and in vivo effects of suspect
      aneugens demonstrates that there are biological mechanisms protecting mammalian
      oocytes from acute exposures to exogenous chemicals. Endocrine disruptors are a
      novel group of compounds that might affect chromosome segregation at meiosis.
      Data on bisphenol-A suggest that such chemicals could be active at low chronic
      exposure levels, but this hypothesis needs to be confirmed by further
      experiments. Experiments on cultured mouse oocytes treated with inhibitors of
      biochemical reactions involved in the regulation of chromosome segregation point
      to possible new mechanisms of action of environmental aneugens.

PMID- 16611131
TI  - Expression of estrogen-regulated genes during development in the mouse uterus
      exposed to diethylstilbestrol neonatally.
AB  - Neonatal diethylstilbestrol (DES) exposure elicits a wide range of abnormalities
      in the female mouse genital tract. This animal model system is suitable for
      investigating the mechanism of DES syndrome in humans. Accumulated evidence has
      shown that critical periods in development are present for distinct and permanent
      alterations in the female genital tract of mice exposed to DES neonatally (DES
      mice). These effects of DES and other estrogens are mainly mediated by estrogen
      receptor alpha (ER alpha) through multiple pathways. Induction of ER alpha by DES
      exposure in neonatal stromal and epithelial cells, and successive premature
      activation of estrogen-regulated genes are thought to be essential to induce the
      abnormalities. Induction of malformation, permanent changes in estrogen-regulated
      genes, such as protooncogenes and growth factors, and carcinogenesis are assumed
      to be interdependent. This review focuses the following topics to discuss the
      molecular basis of DES-induced abnormalities mainly based on the results by
      histochemical techniques in the uterus: spatiotemporal expression of ER alpha and
      coactivators, proteins relating morphogenesis, and estrogen-regulated
      protooncogenes and growth factors.

PMID- 16611132
TI  - Fetal alcohol syndrome: a cautionary note.
AB  - Fetal alcohol syndrome (FAS) is a pattern of anomalies occurring in children born
      to alcoholic women. The main features of this pattern are pre and/or postnatal
      growth retardation, characteristic facial abnormalities, and central nervous
      system dysfunction, including mental retardation. Since its clinical recognition
      in 1973 it has progressed from an unrecognized condition to a major public health
      concern with exaggerated and unfounded claims as to causality and impact. This
      review summarizes some of the basic facts about fetal alcohol syndrome with
      respect to terminology, prevalence, and mechanisms, in the context of exposure
      risk.

PMID- 16611133
TI  - Teratogenic and developmental effects of lithium.
AB  - A review is presented on the effects of lithium in therapeutic doses on the
      outcome of human pregnancy. The results of various studies including cohort,
      prospective, retrospective and small number case reports indicate that lithium is
      a "weak" teratogen in humans. The main effects attributable to lithium are,
      cardiac malformations and babies with increased birth weight. There is a
      possibility that, in particular, lithium may be associated with the Ebstein
      anomaly but present evidence cannot definitely affirm or deny this association.
      Animal studies with lithium using doses comparable to human therapeutic serum
      levels have not reported any abnormalities. However, higher doses have produced
      exencephaly, skeletal and craniofacial defects and abnormalities of blood vessel
      development. Experiments with other vertebrates have shown that lithium affects
      dorsoventral specification and inhibition of vasculogenesis. Both these effects
      can be prevented by pretreatment with myo-inositol indicating that lithium
      interferes with the phosphatidyl inositol cycle. More recent findings have shown
      that the effects of lithium on invertebrates may be mediated through inhibition
      of GSK-3beta in the Wnt-GSK-3 pathway.

PMID- 16611134
TI  - Pleiotropic effects of nifedipine on atherosclerosis.
AB  - Impaired endothelial cell (EC) growth and function have been proposed to be an
      initial event that leads to the development of atherosclerosis. There is a
      growing body of evidence that atherosclerosis is an inflammatory
      fibroproliferative disease, and ECs are target for cytokines and growth factors
      released during inflammation. Recently, nifedipine, one of the most widely used
      dihydropyridine-based calcium antagonists (DHPs) for treatments of patients with
      hypertension, was shown to inhibit vascular inflammation and subsequently improve
      endothelial function in many cardiovascular diseases, thus slowing the
      development and progression of atherosclerosis. However, the molecular mechanisms
      underlying this are not fully understood, because ECs do not possess voltage
      operated L-type calcium channels. In this review, we discuss the pleiotropic
      effects of nifedipine on atherosclerosis, especially focusing on its anti
      oxidative properties.

PMID- 16611135
TI  - Atorvastatin and diabetic vascular complications.
AB  - Statins inhibit 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase, a rate
      limiting enzyme for cholesterol synthesis, and share the common mechanism of
      lowering circulating levels of low-density lipoprotein cholesterol. Among various
      statins, atorvastatin is the most widely used statin for the treatment of
      hypercholesterolemia. Recent clinical trials show that atorvastatin reduces the
      risk of cardiovascular events and slows the progression of atherosclerosis in
      patients with coronary artery diseases. Further, intensive therapy with
      atorvastatin is also associated with an early clinical benefit in patients with
      acute coronary syndrome. These observations support the concept that beyond lipid
      lowering effects of atorvastatin, that is, pleiotropic effects, could contribute
      at least in part to cardiovascular event reduction. Diabetic vascular
      complication is a leading cause of end-stage renal failure, acquired blindness, a
      variety of neuropathies and accelerated atherosclerosis, which could account for
      disabilities and high mortality rates in patients with diabetes. However, whether
      atorvastatin therapy decreases the risk for the development and progression of
      diabetic vascular complications and the way that it might achieve these effects
      are not fully elucidated. In this paper, we focus on diabetic vascular
      complications and review the efficacy and safety of atorvastatin in the treatment
      of these devastating disorders. We further discuss here the possible
      vasculoprotective properties of atorvastatin in patients with diabetes.

PMID- 16611136
TI  - Recent advances in azo dye degrading enzyme research.
AB  - Azo dyes, which are characterized by one or more azo bonds, are a predominant
      class of colorants used in tattooing, cosmetics, foods, and consumer products.
      These dyes are mainly metabolized by bacteria to colorless aromatic amines, some
      of which are carcinogenic, by azoreductases that catalyze a NAD(P)H-dependent
      reduction. The resulting amines are further degraded aerobically by bacteria.
      Some bacteria have the ability to degrade azo dyes both aerobically and
      anaerobically. Plant-degrading white rot fungi can break down azo dyes by
      utilizing a number of oxidases and peroxidases as well. In yeast, a ferric
      reductase system participates in the extracellular reduction of azo dyes.
      Recently, two types of azoreductases have been discovered in bacteria. The first
      class of azoreductases is monomeric flavin-free enzymes containing a putative
      NAD(P)H binding motif at their N-termini; the second class is polymeric flavin
      dependent enzymes which are studied more extensively. Azoreductases from bacteria
      represent novel families of enzymes with little similarity to other reductases.
      Dissociation and reconstitution of the flavin dependent azoreductases demonstrate
      that the non-covalent bound flavin prosthetic group is required for the enzymatic
      functions. In this review, structures and carcinogenicity of azo colorants,
      protein structure, enzymatic function, and substrate specificity, as well as
      application of the azo dyes and azoreductases will be discussed.

PMID- 16611137
TI  - Biochemical and molecular basis of insulin resistance.
AB  - Insulin-resistance is a major problem associated with diabetes and that is
      increasing rapidly worldwide. Insulin is a peptide hormone secreted by the beta
      cells of the pancreatic islets of Langerhans in response to increased circulating
      levels of glucose and amino acids and it is essential for appropriate tissue
      development, growth, and maintenance of whole-body glucose homeostasis by
      regulating carbohydrate, lipid and protein metabolism. Insulin resistance is a
      defect in signal transduction. The signaling mechanisms involved in the various
      biologic responses to insulin remain somewhat elusive. This review focuses on the
      structure and activity of insulin receptor, inheritance of insulin resistance,
      insulin receptor and alleles, enzyme activity in insulin resistance, insulin
      receptor in phosphorylation and relating substrate. We have discussed insulin
      receptor substrate-family (IRS) related to insulin resistance, detail downstream
      signaling effects, GLUT4 vesicle translocation and related events, cytokine
      mediated insulin resistance, and feedback control mechanisms. This review also
      focuses on insulin resistance in obesity-linked metabolic syndrome, insulin
      resistance related to plasma membrane disturbances and insulin resistance for
      exercise and cellular integrity. Finally, we can conclude that insulin resistance
      is really a complex phenomenon in which several genetic defects combine with
      environmental stresses.

PMID- 16611138
TI  - Structure and function of the Epstein-Barr virus transcription factor, EBNA 3C.
AB  - EBNA 3C is one of only nine proteins expressed by the tumourigenic gamma
      herpesvirus Epstein-Barr virus (EBV) during the infection and immortalization of
      human B lymphocytes. In fact, the expression of EBNA 3C has been shown to be
      essential for the B-cell transformation process to take place. The mechanism by
      which EBNA 3C contributes to viral pathogenicity has therefore been the subject
      of intensive research over many years. The first clues on the function of EBNA 3C
      came from analysis of the primary amino acid sequence of EBNA 3C which identified
      a number of domains commonly found in transcriptional regulatory proteins. These
      domains include a proline-rich and a glutamine-proline-rich domain and a putative
      bZIP domain located in the N-terminus of the protein. EBNA 3C has subsequently
      been shown to function as a regulator of both viral and cellular transcription
      and to have potent effects on normal cell-cycle regulatory pathways. This review
      will discuss our current knowledge of the functions of EBNA 3C, the roles played
      by the different domains of EBNA 3C in these functions, and summarize some recent
      work from our laboratory that provides the first structural and functional
      analysis of the putative bZIP domain of EBNA 3C.

PMID- 16611139
TI  - Advances in HTLV-1 peptide vaccines and therapeutics.
AB  - In the past two decades a large initiative has been put forth to understand the
      biological and pathogenic properties of the human T-cell lymphotropic virus type
      1 (HTLV-1); this has ultimately led to the development of various experimental
      vaccination and therapeutic strategies to combat HTLV-1 infection. The focus of
      this work is to outline key targets for the design of therapeutics for HTLV-1,
      such as fusion mediated by the envelope glycoprotein, and to discuss reports of
      novel vaccines or therapeutics. These strategies include peptide, recombinant
      protein, DNA, and viral vectors. The final focus of this review is to acquaint
      the reader with vaccine approaches developed in our laboratory over the last
      decade. These strategies include the development of envelope glycoprotein derived
      B-cell epitopes for the induction of neutralizing antibodies, as well as a
      strategy to generate a multivalent cytotoxic T-lymphocyte (CTL) response against
      the HTLV-1 Tax antigen.

PMID- 16611140
TI  - Transcriptome analyses of human genes and applications for proteome analyses.
AB  - By utilizing recently developed full-length cDNA technologies, large-scale cDNA
      sequencing was carried out by several cDNA projects. Now full-length cDNA
      resources cover the major part of the protein-coding human genes. Comprehensive
      analyses of the collected full-length cDNA data revealed not only the complete
      sequences of thousands of novel gene transcripts but also novel alternatively
      spliced isoforms of hitherto identified genes. However, it was not as easy as
      expected to deduce their encoded amino acid sequences based solely on the full
      length cDNA sequences. It was neither always the case that the longest open
      reading frame corresponded to the real protein coding region nor that the first
      ATG was the translation initiator codon. Also, proteome-wide mass-spectrometry
      analysis has shown that there is an unexpectedly large population of small
      proteins, encoded by so-called upstream open reading frames, within the cell.
      Since sound manual annotations by experts were still indispensable to address
      these problems, an international meeting to make transcriptome-wide functional
      annotations of cDNAs was held, namely the H-invitational. In this meeting,
      functional annotations were made both manually and computationally for most of
      the pre-existing full-length cDNAs collected from world-wide cDNA projects. The
      achieved integrated information for each of the cDNAs was published as a
      database. It was also shown that the full-length cDNA data were useful for
      identifying alternative splicing variants, exact transcriptional start sites of
      the mRNAs and the adjacent promoter regions. Rapidly accumulating genome data as
      well as versatile use of the transcriptome information will shortly lay a firm
      foundation for proteome-level understanding of human gene networks.

PMID- 16611141
TI  - Recombinant antibodies in cancer therapy.
AB  - The application of recombinant immunotoxin and radioimmunoconjugate in Cancer
      therapy has revived the "magic bullet" concept predicted a century ago. Many of
      the recombinant antibodies have received FDA approval for various indication of
      cancer in recent years and numerous others are in clinical trials.

PMID- 16611142
TI  - Cytokine-regulated protein degradation by the ubiquitination system.
AB  - The ubiquitin-mediated protein degradation pathway exerts a wide spectrum of
      effects and modulates a variety of biological processes including cell cycle
      progression, transcriptional regulation, signal transduction, antigen
      presentation, apoptosis (or programmed cell death), oncogenesis, preimplantation,
      and DNA repair. Recently, the importance of deubiquitination mechanism has been
      emerged as an essential regulatory step to control these cellular mechanisms for
      homeostasis. Even though a number of deubiquitinating enzymes have recently been
      isolated, relatively little is known about their substrates and biological
      functions. Identified from yeast to human, deubiquitinating (DUB) enzymes are
      classified into the ubiquitin C-terminal hydrolase (UCH), the ubiquitin-specific
      processing proteases (UBP or USP), Jab1/Pad1/MPN domain containing metallo
      enzymes (JAMM), Otu domain ubiquitin-aldehyde binding proteins (OTU), and Ataxin
      3/Josephin domain containing proteins (Ataxin-3/Josephin). Several members of a
      novel DUB subfamily induced by cytokines in murine lymphocytes have recently been
      identified. In addition, human DUB enzyme DUB-3, highly homologous to USP17 and
      induced by cytokines interleukin (IL)-4 and IL-6, has been recently isolated and
      showed that it has significant homology to the known murine DUB subfamily
      members. Interestingly, both murine DUB and human USP17 subfamily members are
      localized and clustered on murine chromosome 7 and on human chromosomes 4 and 8,
      respectively. This review introduces the reader to provide a great understanding
      of cytokine-inducible DUB enzymes in both mouse and human, and new insights into
      DUB subfamily members.

PMID- 16611144
TI  - Matrix metalloproteinase inhibitors as prospective agents for the prevention and
      treatment of cardiovascular and neoplastic diseases.
AB  - Acting on a broad spectrum of extracellular, intracellular, and membrane
      associated substrates, the matrix metalloproteinases (MMPs) are critical to the
      biological processes of organisms; when aberrantly expressed, many pathological
      conditions may be born or exacerbated. The prospect of MMP inhibition for
      therapeutic benefit in cancer, cardiovascular disease, and stroke is reviewed
      here. MMP inhibitor (MMPI) development constitutes an important branch of
      research in both academic and industrial settings and advances our knowledge on
      the structure-function relationship of MMPs. Targeting MMPs in disease treatment
      is complicated by the fact that MMPs are indispensable for normal development and
      physiology and by their multi-functionality, possible functional redundancy or
      contradiction, and context-dependent expression and activity. This complexity was
      revealed by previous efforts to inhibit MMP activity in the treatment of cancer
      patients that yielded unsatisfactory results. This review focuses on MMPI
      development since the late 90s, in terms of natural products and their
      derivatives, and synthetic compounds of low molecular mass incorporating specific
      zinc-binding groups (ZBGs). A few polyphenols and flavonoids that exhibit MMPI
      activities may have chemopreventive and neuro- and cardiovascular-protective
      effects. A new generation of potent and selective MMPIs with novel ZBGs and
      inhibition mechanisms have been designed, synthesized, and tested. Although only
      one collagenase inhibitor (Periostat, doxycycline hyclate) has been approved by
      the Food and Drug Administration as a drug for the treatment of periodontal
      disease, new hope is emerging in the form of natural and synthetic MMPIs for the
      prevention and treatment of stroke, cardiovascular disease, cancer, and other
      medical conditions.

PMID- 16611145
TI  - Structure- and fragment-based approaches to protease inhibition.
AB  - Proteases are essential enzymes which regulate physiological processes such as
      inflammation, infection, fertilization, allergic reactions, cell growth and
      death, blood clotting, tumor growth and bone remodeling. The protease family
      consists of six major classes of enzymes which are aspartic-, serine-, cysteine-,
      threonine-, glutamic-, and metallo-proteases, all which are implicated in disease
      propagation. Therefore, protease inhibitors have been of great interest as
      possible targets for the development of novel therapies. Although, many protease
      inhibitors have followed a structural design based on either a peptidic or
      peptidomimetic backbone, other chemical scaffolds have recently emerged.
      Utilizing structure- and fragment-based design guided by X-ray crystallography,
      NMR spectroscopy, computational and/or extended tethering approaches, potential
      non-peptidic therapeutic agents could be identified. In this review, we will
      report on the recent developments of nonpeptidic cysteine- and metallo- protease
      inhibitors, focusing on their design by using such strategies.

PMID- 16611146
TI  - Inhibitors of cysteine proteases.
AB  - The roles of cysteine proteases (CP) as protein degrading and protein processing
      enzymes both in physiological and pathological processes of mammals are well
      known. Furthermore, the key roles of CP;s in the life cycles of infectious agents
      like protozoa and viruses turn them into new important targets for anti-infective
      drugs. Thus, the effective inhibition of pathologically relevant cysteine
      proteases has raised increasing interest in drug development. One strategy to
      create CP inhibitors is the use of electrophilic moieties, which covalently bind
      to the cysteine residue of the active site of the target protease. In a previous
      approach we have selected the aziridine-2,3-dicarboxylic acid as weak
      electrophilic inhibitor fragment. In order to achieve effective enzyme inhibition
      this electrophile was incorporated into peptidic or peptidomimetic sequences
      addressing the substrate binding sites of the protease. High selectivity could be
      obtained with compounds, which bind into both the primed and non-primed substrate
      binding pockets. In a second approach the alpha,beta-unsaturated ketone of the
      well-known diuretic drug ethacrynic acid was found to be another appropriate
      electrophilic moiety. Derivatives thereof turned out to be new non-peptidic CP
      inhibitors. Results of inhibition assays obtained with these two inhibitor series
      on various proteases of human, protozoan, and viral origin, theoretical studies
      to investigate binding modes and inhibition mechanisms, and structure-activity
      relationships are presented. Furthermore, the results of in vitro assays on
      respective pathogens as well as the results of first toxicity studies are
      summarized.

PMID- 16611147
TI  - Non-covalent cathepsin K inhibitors for the treatment of osteoporosis.
AB  - Cathepsin K is a cysteine protease that plays an important role in the
      pathological process of bone resorption. Selective cathepsin K inhibitors may
      thus provide great potential in the treatment of osteoporosis. Pharmaceutical
      interest in this area is highlighted by the rising number of publications and
      patent applications. Most recently, the interim results of three clinical trials
      conducted by Novartis, GlaxoSmithKline, and Merck have strengthened the
      validation of the target for the therapeutic intervention of osteoporosis. Here
      we report a series of Cbz-leucyl-(4-piperidinylphenyl)aminoethyl amides based on
      dipeptidyl anilines for cathepsin K inhibition. These new non-covalent inhibitors
      exhibit single digit nM inhibition of the cathepsin family. Molecular modeling
      studies on the interactions responsible for the potency of these inhibitors for
      cathepsin K will be also discussed.

PMID- 16611148
TI  - Characterization and inhibition of SARS-coronavirus main protease.
AB  - Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused
      by a novel human coronavirus (CoV). During the 2003 epidemic, the disease rapidly
      spread from its origin in southern China to other countries and affected almost
      8000 patients, which resulted in about 800 fatalities. A chymotrypsin-like
      cysteine protease named 3C-like protease (3CLpro) is essential for the life cycle
      of the SARS-CoV. This main protease is responsible for maturation of functional
      proteins and represents a key anti-viral target. HPLC and fluorescence-based
      assays have been used to characterize the protease and to determine the potency
      of the inhibitors. The fluorogenic method monitoring the increase of fluorescence
      from the cleavage of a peptide substrate containing an Edans-Dabcyl fluorescence
      quenching pair at two ends has enabled the use of high throughput screening to
      speed up the drug discovery process. Several groups of inhibitors have been
      identified through high throughput screening and rational drug design approaches.
      Thus, alpha,beta-unsaturated peptidomimetics, anilides, metal-conjugated
      compounds, boronic acids, quinolinecarboxylate derivatives,
      thiophenecarboxylates, phthalhydrazide-substituted ketoglutamine analogues,
      isatin and natural products have been identified as potent inhibitors of the SARS
      CoV main protease. The different classes of inhibitors reported in these studies
      are summarized in this review. Some of these inhibitors could be developed into
      potential drug candidates, which may provide a solution to combat possible
      reoccurrence of the SARS and other life-threatening viruses with 3CL proteases.

PMID- 16611149
TI  - Inhibitors and modulators of beta- and gamma-secretase.
AB  - Most gene mutations associated with Alzheimer's disease point to the metabolism
      of amyloid precursor protein as potential cause. The beta- and gamma-secretases
      are two executioners of amyloid precursor protein processing resulting in amyloid
      beta. Significant progress has been made in the selective inhibition of both
      proteases, regardless of structural information for gamma-secretase. Several
      peptidic and non-peptidic leads were identified and first drug candidates are in
      clinical trials. This review focuses on the developments since 2003.

PMID- 16611150
TI  - Targeting serine proteases in asthma.
AB  - Leukocytes and lung structural cells contribute to the pathophysiology of asthma
      through the production of numerous mediators including serine proteases. Such
      proteases include mast cell tryptase and chymase; neutrophil elastase, cathepsin
      G and myeloblastin (proteinase 3); bronchial epithelial cell-derived
      transmembrane protease, serine 11D (human airway trypsin-like protease);
      cytotoxic T lymphocyte- and natural killer cell-derived granzyme B; and,
      eosinophil serine protease 1 (testisin). Considerable effort to develop potent
      and selective inhibitors, mostly non-peptidic, especially targeting tryptase and
      chymase have been made in the last few years. This review presents promising
      inhibitors, currently in the research and development pipeline. Some endogenous
      inhibitors and other compounds purified from non-human species are also
      discussed.

PMID- 16611151
TI  - The management of phosphodiesterase-5 (PDE5) inhibitor failure.
AB  - The oral phosphodiesterase type 5 (PDE5) inhibitors have made a valuable
      contribution to the treatment of erectile dysfunction (ED). PDE5 inhibitors
      enhance cavernosal smooth muscle relaxation, vasodilatation and penile erection.
      However, PDE5 inhibitors are not always effective. Decreased efficacy, cost,
      incorrect administration, lack of sexual stimulation, vascular risk factors
      associated with ED and vascular or neurogenic diseases are causes of PDE5
      inhibitor failure. Tachyphylaxis may also occur. This is defined as reduced
      tissue responsiveness to a drug in the presence of a constant concentration of
      this drug. Treatment failure may cause considerable distress. If dose titration,
      more attempts and continuous dosing of PDE5 inhibitors (taken on a daily basis)
      fail to resolve the initial PDE5 inhibitor failure, clinicians need to consider
      alternative treatments. These include sublingual apomorphine,
      intracavernosal/intraurethral pharmacotherapy, vacuum devices, the insertion of a
      prosthesis and penile vascular surgery. Combination therapy like prostaglandin
      E(1) (PGE(1)) with doxazosin (dox; an alpha-1-blocker) or ketanserin (ketan; a 5
      HT(2) antagonist) as well as other pro-erection agents, like Endothelin-1
      antagonists, angiotensin II antagonists (valsartan/losartan), adrenomedullin, Rho
      kinase inhibitors and nitric oxide (NO) donors may be beneficial in the treatment
      of ED. However, these combination therapies need to be validated. Adding an
      androgen to a PDE5 inhibitor may help when circulatory testosterone levels are
      low. The early use of PDE5 inhibitors in patients with hypertension,
      hyperlipidaemia or diabetes with concomitant ED and treating these risk factors
      may improve corporeal blood flow and lead to long-term preservation of cavernosal
      function. Therefore, the efficacy of PDE5 inhibitors may be maintained. Targeting
      the risk factors of ED (similar to those for arteriosclerosis) in the early
      stages of the disease may prevent the development or decrease the severity of ED.

PMID- 16611152
TI  - Pharmacological management of no reflow during percutaneous coronary
      intervention.
AB  - Angiographic no reflow is a recognized phenomenon during percutaneous coronary
      intervention (PCI). It usually follows successful lesion dilation and, by
      definition, it represents a reduction in epicardial coronary blood flow in the
      absence of identifiable dissection, obstruction or distal vessel cut off
      (indicative of distal embolisation). No reflow appears to be more commonly
      associated with PCI for acute myocardial infarction and PCI for saphenous vein
      graft occlusions. While the exact mechanism of no reflow is unknown, theoretical
      causes include local humoral and microembolic effects leading to microcirculatory
      dysfunction. As the process is multifactorial, various therapeutic strategies are
      required in different situations. The present day pharmacological management
      involves the use of vasodilators including nitrates, verapamil, papaverine,
      adenosine, nicardipine and sodium nitroprusside, but interestingly a
      vasoconstrictor like epinephrine may also have a role. Glycoprotein IIb/IIIa
      platelet receptors antagonist have shown a powerful de-thrombotic effect, and the
      intracoronary administration appears to be particularly promising. We review the
      pathogenesis of a reduced epicardial flow during PCI and focus on those drugs
      that have been studied for the treatment of no reflow. Although no double blind,
      randomized trial has been conducted to assess any of these agents, or to
      determine the appropriate dosage, we try to identify some useful conclusions from
      the published evidence.

PMID- 16611153
TI  - Plasminogen activator system and vascular disease.
AB  - Vascular diseases, such as atherosclerosis, thromboembolic disorders and stroke,
      in addition to surgical procedures such as restenosis, all share the plasminogen
      activator system as a central component in the pathogenesis of vascular injury.
      Since the development of plasminogen deficient mice our knowledge of the effects
      of this proteolytic system in cardiovascular disease has vastly increased. The
      plasminogen activator system plays a key role in vascular homeostasis and
      constitutes a critical response mechanism to cardiovascular injury. The central
      components of the PA system are the proteolytic activators, urokinase-plasminogen
      activator (u-PA) and tissue-type plasminogen activator (t-PA), plasminogen (plg)
      and its degradation product, plasmin, together with the major inhibitors of this
      system, plasminogen activator inhibitor-1 and -2 (PAI-1, PAI-2). An extensive
      network of additional proteases, inhibitors, receptors and modulators directly
      associate and are influenced by the PA system, the largest group being the Matrix
      Metalloproteinases (MMPs) and their respective inhibitors the Tissue inhibitors
      of MMPs (TIMPS).

PMID- 16611154
TI  - Migraine: current therapeutic targets and future avenues.
AB  - Migraine is characterized by attacks of intense pulsatile and throbbing headache,
      typically unilateral in nature with or without aura. Migraine affects a
      substantial fraction (10-20 %) of the world population (more women than men).
      With regard to the pathophysiology of migraine, several theories have been
      proposed; the major three are vascular (due to cerebral vasodilatation),
      neurological (abnormal neurological firing) and neurogenic dural inflammation
      (release of inflammatory neuropeptides). The drugs used to treat migraine can be
      divided into two groups: agents that abolish the acute migraine headache and
      agents aimed at prevention. The acutely acting antimigraine agents (5-HT(1B/1D)
      receptor agonists) stimulated research interest in the field of migraine.
      Currently prophylactic treatments for migraine include calcium channel blockers,
      5-HT(2) receptor antagonists, beta-adrenoceptor blockers and gamma-amino butyric
      acid (GABA) agonists. Unfortunately, many of these treatments are non-specific
      and not always effective. Despite progress, the complex etiology of migraine
      requires further research, the condition often remains undiagnosed and available
      therapies are underused. In this review, the evidence that linked the different
      theories of migraine with its pathophysiology is considered. Furthermore, the
      present therapeutic targets and future approaches for the acute and prophylactic
      treatment of migraine are critically evaluated.

PMID- 16611155
TI  - Pharmacotherapy of abdominal aortic aneurysms.
AB  - Aortic aneurysms account for 10,000 deaths annually in the UK, due to rupture. At
      present the only effective therapeutic strategy to treat abdominal aortic
      aneurysms is to surgically repair them; this carries an elective mortality of up
      to 10%. Recent advances in vascular biology have led to a greater understanding
      of the pathophysiological process that causes aortic aneurysms to expand and
      rupture. Key pathological processes include widespread aortic inflammation,
      proteolytic degradation of the extracellular matrix, neovascularisation and
      generation of reactive oxygen species. Identification of these processes has lead
      to pharmacological strategies to prevent aneurysm expansion and rupture. Many of
      these strategies have undergone proof of concept in animal models and some have
      now entered clinical trials. This review outlines current thinking regarding the
      molecular events leading to aneurysm expansion and explains how these processes
      may be inhibited. Experimental data on agents retarding aneurysm expansion in
      animal models are discussed. A significant proportion of the review details
      pharmacological agents that have undergone or are undergoing clinical trials.
      Pharmacological treatment for abdominal aneurysms is urgently required given the
      number of small aneurysms being diagnosed by screening programmes. This is a
      rapidly evolving field and one in which translation from experimental research to
      clinical practice is anticipated within 5 years.

PMID- 16611156
TI  - Fine tuning therapeutic targeting of the sphingolipid biosynthetic pathway to
      treat atherosclerosis.
AB  - The accumulation of sphingolipids, including sphingomyelin and
      glycosphingolipids, in atherosclerotic lesions is well known. Plasma
      sphingomyelin concentration is correlated with atherosclerosis development and is
      an independent predictor of coronary artery disease. Similarly, plasma
      glycosphingolipid levels are increased in conditions associated with
      atherosclerosis risk. Recent studies have focused on understanding the mechanisms
      by which specific intermediates and end-products of the sphingolipid biosynthetic
      pathway, such as sphingomyelin, glycosphingolipids, ceramide and sphingosine-1
      phosphate may modulate vascular biology and atherosclerosis. Here we focus on
      recent work indicating that pharmacological modulation of the sphingolipid
      biosynthetic pathway could offer a novel treatment for atherosclerosis or, at the
      very least, provide mechanistic insights concerning the etiology of this disease
      which is the major cause of death in developed countries.

PMID- 16611157
TI  - Blood pressure reduction in the primary and secondary prevention of stroke.
AB  - Control of hypertension is well established for the primary prevention of stroke.
      Prior studies, on the other hand, conflict over whether hypertension remains a
      risk factor for recurrent stroke and if blood pressure reduction is associated
      with better outcomes in this subset of patients. We review current evidence
      regarding the role of BP lowering for primary and secondary prevention of stroke.
      Current evidence amassed from both primary and secondary prevention trials
      demonstrate that BP reduction is a crucial common element in overall reduction of
      stroke risk.

PMID- 16611158
TI  - Postprandial hypotension - novel insights into pathophysiology and therapeutic
      implications.
AB  - Postprandial hypotension is a frequent disorder, occurring in approximately 40%
      of nursing-home residents, and represents a major cause of morbidity and
      mortality. Current approaches to management are suboptimal. While it has been
      generally assumed that ingestion of carbohydrate has the greatest effect, the
      fall in blood pressure (BP) does not appear to be mediated by the consequent
      elevations in blood glucose and insulin. Moreover, there is evidence that fat may
      decrease BP to a comparable extent to carbohydrate, although onset of the
      response may be slower, and that the response is affected by the type of
      carbohydrate. It has recently been established that the rate of nutrient delivery
      from the stomach into the small intestine is an important determinant of the
      hypotensive response to carbohydrate, so that the magnitude of the fall in BP and
      rise in heart rate is greater when gastric emptying is relatively more rapid. In
      both healthy elderly subjects and patients with type 2 diabetes, the fall in BP
      is attenuated when gastric emptying and small intestinal carbohydrate absorption
      are slowed by dietary (e.g. guar) or pharmacological (e.g. acarbose) means.
      Conversely, gastric distension attenuates the postprandial fall in BP. Strategies
      for the treatment of postprandial hypotension should, therefore, potentially be
      directed at (i) meal composition, particularly carbohydrate type and content,
      (ii) slowing gastric emptying and/or small intestinal carbohydrate absorption
      and/or (iii) increasing postprandial gastric distension.

PMID- 16611159
TI  - Metabolic transformation and mechanism of action of mononitroso caffeidine- a new
      interpretation.
AB  - Although caffeine is not carcinogenic, its hydrolysed product, caffeidine causes
      human cancer, possibly through endogenous nitrosation to form mononitroso
      caffeidine (MNC). MNC undergoes enzymatic demethylation and reacts with cellular
      nucleophiles, notably DNA, via the formation of a putative imidazole diazonium
      ion. Its interaction with proteins has not been reported. The present work is
      based on the hypothesis that some active metabolites of MNC covalently interact
      with cellular DNA and/or proteins to initiate carcinogenesis. We report here the
      synthesis of a possible reactive metabolite of MNC, viz., N, 1-methyl-4(N-methyl
      N-nitrosamino)-imidazole-5-carboxylic acid (MNIC). Its structure has been
      determined by uv, ir, nmr and mass spectral analyses and its interaction with egg
      albumin and human serum protein has been examined by uv and CD spectroscopy. We
      concluded that metabolic activation of MNC occurs through the formation of MNIC.
      Avoiding consumption of salted tea or coffee that prevents the intake of
      caffeidine will possibly eliminate the risk of MNC carcinogenicity.

PMID- 16611160
TI  - Family C 7TM receptor dimerization and activation.
AB  - The family C seven transmembrane (7TM) receptors constitutes a small and
      especially well characterized subfamily of the large 7TM receptor superfamily.
      Approximately 50% of current prescription drugs target 7TM receptors, this
      biologically important family represents the largest class of drug-targets today.
      It is well established that family C 7TM receptors form homo- or hetero-dimers on
      the cell surface of living cells. The large extra-cellular domains (ECD) have
      been crystallized as a dimer in the presence and absence of agonist. Upon agonist
      binding, the dimeric ECD undergoes large conformational changes that lead to
      receptor activation. Despite extensive studies of the receptor transmembrane
      domain, several key features, including the exact organization of the complete
      receptor dimer, the sequence of events leading to receptor activation, and the
      functional significance of dimerization, have yet to be fully defined. This
      review presents the biochemical support for family C 7TM receptor dimerization
      and discusses its importance for receptor biosynthesis, surface expression,
      ligand binding and activation, since lessons learnt here may well be applicable
      to the whole superfamily of 7TM receptors.

PMID- 16611161
TI  - Matrix metalloproteinases in cancer metastasis: molecular targets for prostate
      cancer prevention by green tea polyphenols and grape seed proanthocyanidins.
AB  - Matrix metalloproteinases (MMP) play a crucial role in the development and
      metastatic spread of cancer. One of the earliest events in the metastatic spread
      of cancer is the invasion through the basement membrane and proteolytic
      degradation of the extracellular matrix proteins, such as, collagens, laminin,
      elastin and fibronectin etc, and non-matrix proteins. MMPs are the important
      regulators of tumor growth, both at the primary site and in distant metastases.
      Given the clear implications of MMPs in many human cancers, MMPs remain important
      targets of cancer therapy. Metastatic spread of cancer continues to be the
      greatest barrier in prevention or cure of cancer. The recognition that MMPs
      facilitate tumor cell growth, invasion and metastasis of cancer has led to the
      development of MMP inhibitors as cancer therapeutic agents. Understanding the
      molecular mechanism of metastasis is also crucial for the design and effective
      use of novel therapeutic strategies to combat metastases. In this short review
      article, we discuss the evidences that MMPs are associated with cancer metastasis
      and that they make a functional contribution to the process. Further, since
      considerable interest among human population is increasing with regard to the use
      of dietary botanical supplements for the prevention of age-associated diseases
      like some forms of cancer, we also discuss the beneficial effects of dietary
      botanicals, such as green tea polyphenols and grape seed proanthocyanidins, in
      chemoprevention of cancer with particular emphasis on the involvement of MMPs in
      prostate cancer.

PMID- 16611162
TI  - Recent advances on neural tube defects with special reference to Valproic Acid.
AB  - Epilepsy is a common medical problem and many studies have demonstrated that
      infants of women with epilepsy (WWE) have a two to threefold higher risk of
      congenital malformations compared with the background population. The majority of
      WWE have normal, healthy children. However, WWE have an increased risk of
      congenital malformations. Congenital malformations are twice as common in infants
      exposed to antiepileptic drugs in utero. A variety of congenital malformations
      have been reported, with a particular preponderance of orofacial clefts.
      Valproate is often associated with the development of neural tube defects. In
      this review, we analyse the problem of neural tube defects and report in detail
      the main pathogenetic theories about the onset of this type of congenital
      malformation. There is strong evidence for a protective effect of adequate folate
      consumption.

PMID- 16611163
TI  - Selective modulators of PPAR activity as new therapeutic tools in metabolic
      diseases.
AB  - Peroxisome Proliferator Activated Receptors (PPARs) are regulators of metabolic
      pathways mainly of lipid metabolism and energy balance. Their medical importance
      is given by the fact that they have been implicated in development of insulin
      resistance, obesity and atherosclerosis. In recent years, major progress has been
      made in understanding the molecular basis of the function of these receptors. As
      a result of structural studies and identification of putative natural as well as
      synthetic ligands and activators of PPARs a new concept emerged and new drugs are
      on their ways to the clinic. The concept of Selective PPAR Modulators (SPPARM)
      was suggested by analogy to Selective Estrogen Receptor Modulators (SERM).
      SPPARMs activate the receptors in distinct ways leading to differential gene
      expression and biological response. The key features in understanding their
      action is most likely at the molecular details of ligand binding and the
      subsequently induced conformational changes as well as cofactor binding. A key
      aspect of this is that unlike classical steroid hormone receptors such as the
      retinoic acid receptor, the PPAR receptors have a rather large ligand-binding
      pocket which is not filled with the ligand entirely and the ligand also
      stabilizes the receptor's structure. The liganded receptor can have distinct
      conformations and this leads to different binding affinities for the various
      cofactors (coactivators and corepressors). In this review, we will introduce this
      concept, review the literature that supports it and present an overview of the
      receptor selective ligands including data about their mechanism of action and
      biological effects.

PMID- 16611164
TI  - Activin receptor-like kinases: structure, function and clinical implications.
AB  - The transforming growth factor-beta (TGF-beta) superfamily regulates a multitude
      of cellular processes from fertilization to adulthood in vertebrates. Signaling
      by the TGF-beta superfamily occurs via formation of heteromeric complexes
      consisting of type I and type II receptors. The type I receptors, referred to as
      activin receptor-like kinases (ALK), lie at the epicenter of the signaling
      cascade as they transduce TGF-beta signals to intracellular regulators of
      transcription known as Smad proteins. Currently, seven ALKs have been identified
      in mammals. Structurally, ALKs possess an extracellular binding domain, a
      transmembrane domain, a GS domain that serves as the site of activation by type
      II receptors, and a kinase domain that activates downstream signaling molecules.
      ALKs mediate the effect of TGF-beta superfamily on a variety of cellular
      processes such as proliferation, differentiation, apoptosis, adhesion and
      migration, and therefore play important roles in many biological processes. Some
      ALKs have been implicated in several disorders, including tumorigenesis,
      hemorrhagic telangiectasia (HHT), immune and renal diseases, and skeletal
      malfunctions, suggesting that these receptors can be used as drug targets.

PMID- 16611165
TI  - The roles of parathyroid hormone and calcitonin in bone remodeling: prospects for
      novel therapeutics.
AB  - Inappropriate regulation of the bone resorption and bone formation processes that
      occur as a normal part of bone remodeling can lead to net bone loss, as found in
      osteoporosis. Parathyroid hormone (PTH) and calcitonin (CT) are two peptide
      hormones that play important roles in calcium homeostasis through their actions
      on osteoblasts (bone forming cells) and osteoclasts (bone resorbing cells),
      respectively. Paradoxically, even though genetic deletion of either PTH or CT
      produces mice with increased bone mass (presumably through different mechanisms),
      derivatives of both PTH and CT have now been approved for clinical use in the
      treatment of bone loss in osteoporosis. In this review, we focus on the biology
      and pharmacology of these two peptides. Specifically, we sequentially address the
      following three topics in detail: (1) the biological mechanisms of action of PTH
      and CT, focusing on data from in vitro studies and animal models; (2) the
      clinical utility of PTH and CT in treating osteoporosis, examining how their
      pharmacological efficacy correlates with our understanding of their biological
      mechanism of action; and (3) future prospects for combination therapy,
      alternative formulation of PTH and CT into oral and transdermal therapies, and
      replacement of PTH and CT with modified peptides or small molecules. The past
      four years have witnessed dramatic advances in each of these three areas, and the
      review places in context the challenges that lie ahead for this complicated, but
      clinically-relevant field.

PMID- 16611166
TI  - Role of antioxidants, essential fatty acids, carnitine, vitamins, phytochemicals
      and trace elements in the treatment of diabetes mellitus and its chronic
      complications.
AB  - Nowadays, the treatment of diabetes mellitus is based on the variable use and
      combination of diet, antidiabetic oral agents (metformin, sulphanylureas,
      glynides, acarbose and thiazolidinediones) and insulin or its analogs, depending
      on the type of diabetes and the needs of the patient. The prevention and
      treatment of chronic micro- and macrovascular complications, on the other hand,
      is based on the achievement and maintenance of an optimal glycaemic control and
      requires the combined use of adjunctive therapy such as antihypertensive drugs
      and cholesterol-lowering medications. Furthermore, several herbal preparations
      and dietary supplements, such as antioxidants, essential fatty acids, lipid
      metabolism activators, vitamins and trace elements, are advertised and prescribed
      to patients as a useful adjuvant to a diabetic diet and conventional medications
      in order to improve glycaemic control and reduce the impact of chronic
      complications. In this regard, we have attempted to review the current concepts
      dealing with the usefulness of these complementary therapies in treating diabetic
      patients.

PMID- 16611167
TI  - Roles of type 10 17beta-hydroxysteroid dehydrogenase in intracrinology and
      metabolism of isoleucine and fatty acids.
AB  - Human type 10 17beta-hydroxysteroid dehydrogenase (HSD) is a homotetrameric
      protein located in mitochondria. This enzyme was alternatively named short chain
      L-3-hydroxyacyl-CoA dehydrogenase (SCHSD). This NAD(H)-dependent dehydrogenase is
      essential for the metabolism of branched-chain fatty acids and isoleucine, and is
      expressed in a variety of tissues, e.g., prostate, brain, liver, and heart. This
      enzyme inactivates 17beta-estradiol and exhibits a strong oxidative 3alpha-HSD
      activity to convert 5alpha-androstanediol and allopregnanolone into 5alpha
      dihydrotestosterone (5alpha-DHT) and 5alpha-dihydroprogesterone, respectively, in
      living cells. Certain malignant prostatic epithelial cells and activated
      astrocytes in Alzheimer's disease patient's brain contain extraordinarily high
      levels of this enzyme. This mitochondrial dehydrogenase enables prostate cancer
      cells to generate 5alpha-DHT in the absence of testosterone. Its inactivation of
      allopregnanolone is important to the modulation of GABA(A) receptor. Among
      steroidogenic enzymes 17beta-HSD10 plays a significant part in the
      intracrinology. Although this protein has an affinity for amyloid-beta peptide,
      its role in the pathogenesis of Alzheimer's disease is far from clear. Additional
      knowledge of this versatile enzyme would provide the foundation for designing new
      drugs aimed at treating some neurological diseases and certain types of cancers.

PMID- 16611168
TI  - Targeting type 1 diabetes before and at the clinical onset of disease.
AB  - Autoimmune type 1 diabetes is strongly associated with a number of immune
      abnormalities that manifest themselves before and at the time of clinical
      diagnosis. The clinical onset is associated with a major loss of the pancreatic
      islet beta cells. Insulin treatment is the only treatment option since numerous
      trials with agents that suppress or modulate immune function have failed to
      preserve beta cell function long term. Recent studies suggest that it is possible
      to predict clinical onset of diabetes by combining genetic with autoantibody
      testing. In this review we will summarize current and future drug targets for
      subjects at risk for type 1 diabetes as well as for subjects with recent onset
      disease. We will also discuss the possible importance of initiating as well as
      contributing factors such as reactive oxygen species and modified autoantigens.
      It is speculated that drug targets of factors important to disease pathogenesis
      may provide safe and effective adductive treatment to preserve beta cell function
      in autoantibody positive subjects who are at maximum risk for disease.

PMID- 16611169
TI  - Our favourite alternative splice site.
AB  - Alternative splicing is a widespread mechanism in mammals that generates several
      mRNAs from one gene, thereby creating genetic diversity of the genome. Variant
      splice patterns are often specific to different stages of development or
      particular tissues, and alternative splicing defects are being more frequently
      detected in genetic diseases and cancers. The increasingly important role of
      alternative splicing in the function and the regulation of cellular process makes
      it critical to have an easy-to-use data repository for the biological and medical
      research communities. We have compared web resources that give access to
      information on alternatively spliced genes, and the FAST DB (Friendly Alternative
      Splicing and Transcripts DataBase) site came out as our favourite.

PMID- 16611170
TI  - Mercy mercy me: social injustice and the prevention of environmental pollutant
      exposures among ethnic minority and poor children.
AB  - Children's lead and pesticide exposures are used as examples to examine social
      disparities in exposure reduction efforts as well as environmental policies
      impacting children in poverty and minority children. The review also presents an
      estimate of the effect of social disparities in lead exposure on standardized
      test performance. Because including measures of pollutants with potential
      behavioral effects can alter the observed effects of race/ethnicity, income, and
      other variables, suggestions are made for including measures of pollutants in
      longitudinal studies and studies of multiple and cumulative risk. Continued basic
      research on developmental correlates and effects of pollution exposure,
      participatory action-research with at-risk and underrepresented populations, and
      contributions to public awareness and education are important leadership areas
      for developmental researchers.

PMID- 16611171
TI  - The birth of words: ten-month-olds learn words through perceptual salience.
AB  - A core task in language acquisition is mapping words onto objects, actions, and
      events. Two studies investigated how children learn to map novel labels onto
      novel objects. Study 1 investigated whether 10-month-olds use both perceptual and
      social cues to learn a word. Study 2, a control study, tested whether infants
      paired the label with a particular spatial location rather than to an object.
      Results show that 10-month-olds can learn new labels and do so by relying on the
      perceptual salience of an object instead of social cues provided by a speaker.
      This is in direct contrast to the way in which older children (12-, 18-, and 24
      month-olds) learn and extend new object names.

PMID- 16611172
TI  - Regression and reorganization of intonation between 6 and 23 months.
AB  - The purpose of this study was to describe the pattern in which English-speaking
      children acquire intonation. A second goal was to account for emerging intonation
      from a theoretical perspective. Six groups of 10 children each between the ages
      of 6 and 23 months participated in individual play sessions with their mothers
      and an experimenter. Pitch contours were acoustically analyzed in monosyllabic
      utterances produced by each child. The observed nonlinear shape of intonation
      development suggested a linguistically based pattern of regression and
      reorganization. However, the precocious expression of intonation in the youngest
      infants also pointed to the role of physiological universals and emotional
      experience. It is concluded that children's early intonation reflects biological,
      affective, and linguistic influences.

PMID- 16611173
TI  - Newborns' face recognition: role of inner and outer facial features.
AB  - Existing data indicate that newborns are able to recognize individual faces, but
      little is known about what perceptual cues drive this ability. The current study
      showed that either the inner or outer features of the face can act as sufficient
      cues for newborns' face recognition (Experiment 1), but the outer part of the
      face enjoys an advantage over the inner part (Experiment 2). Inversion of the
      face stimuli disrupted recognition when only the inner portion of the face was
      shown, but not when the whole face was fully visible or only the outer features
      were presented (Experiment 3). The results enhance our picture of what
      information newborns actually process and encode when they discriminate, learn,
      and recognize faces.

PMID- 16611174
TI  - Stability, change, and correlates of the peer relationships of young children
      with mild developmental delays.
AB  - The peer relationships of young children with mild developmental (cognitive)
      delays recruited at 4-6 years of age were examined in a longitudinal study across
      a 2-year period. Results revealed only modest increases in children's peer
      interactions, a high degree of intraindividual stability, and the existence of a
      poorly organized and conflict-prone pattern of peer interactions. Child cognitive
      and language levels as well as family stress and support were associated with
      children's peer interactions. A subgroup was identified of initially low
      interactors who were at especially high risk for future peer interaction
      problems. These findings further underscore the importance of designing and
      implementing early intervention programs in the area of peer relationships for
      children with mild developmental delays.

PMID- 16611175
TI  - Getting there faster: 18- and 24-month-old infants' use of function words to
      determine reference.
AB  - Infants of 18 and 24 months acquiring English were tested in a preferential
      looking task on their ability to detect ungrammaticalities caused by manipulating
      a single function word in sentences. Infants heard grammatical sentences in which
      the determiner the preceded a target noun, as well as three ungrammatical
      conditions in which the was either dropped, replaced by a nonsense function word
      (el), or replaced by an alternate English function word (and). Both the 18- and
      24-month-old infants oriented faster and more accurately to a visual target
      following grammatical sentences. The results suggest that by 18 months of age,
      infants use their knowledge of determiners in sentence computation and in
      establishing reference.

PMID- 16611176
TI  - Developmental and individual differences in conditional reasoning: effects of
      logic instructions and alternative antecedents.
AB  - In Study 1, 10-, 13-, and 16-year-olds were assigned to conditions in which they
      were instructed to think logically and provided alternative antecedents to the
      consequents of conditional statements. Providing alternatives improved reasoning
      on two uncertain logical forms, but decreased logical responding on two certain
      forms; logic instructions improved reasoning among adolescents. Correlations
      among inferences and verbal ability were found primarily when task conditions
      created conflict between automatic and controlled inferences. In Study 2, when
      the cognitive demands of the logic instructions were reduced, 10-year-olds made
      more logically correct inferences, but only when a conditional's consequents were
      strongly associated with alternative antecedents. Discussion focuses on the
      ability to inhibit invited inferences and the role of automatically activated
      memories.

PMID- 16611177
TI  - Maternal accuracy in predicting toddlers' behaviors and associations with
      toddlers' fearful temperament.
AB  - Past research provides associations between maternal parenting behaviors and
      characteristics such as depression and toddlers' fearful temperament. Less is
      known about how maternal cognitive characteristics and normal personality relate
      to fearful temperament. This study examined associations among the maternal
      cognitive characteristic of accuracy, maternal personality, toddler gender,
      context, and 24-month-old toddlers' fearful temperament. Mothers were more
      accurate in predicting their daughters' emotional reactions in fear-eliciting
      contexts. High maternal approach personality was related to increased maternal
      accuracy for boys. High maternal approach personality, in conjunction with lower
      accuracy, however, was associated with higher levels of toddlers' fearful
      temperament. Results suggest implications for the current understanding of
      toddlers' fearful temperament.

PMID- 16611178
TI  - Social information processing and coping strategies of shy/withdrawn and
      aggressive children: does friendship matter?
AB  - The primary objectives of this investigation were to examine the attributions,
      emotional reactions, and coping strategies of shy/withdrawn and aggressive girls
      and boys and to examine whether such social cognitions differ within the
      relationship context of friendship. Drawn from a sample of fifth and sixth
      graders (M age = 10.79 years; SD = .77), 78 shy/withdrawn, 76 aggressive, and 85
      control children were presented with hypothetical social situations that first
      involved unfamiliar peers, and then a mutual good friend. Results revealed group
      and gender differences and similarities, depending on the relationship context.
      From our findings emerges a central message: friends' involvement during
      interpersonal challenges or stressors mitigates children's attributions,
      emotions, and coping responses.

PMID- 16611179
TI  - Early risk, attention, and brain activation in adolescents born preterm.
AB  - The relations among early cumulative medical risk, cumulative environmental risk,
      attentional control, and brain activation were assessed in 15-16-year-old
      adolescents who were born preterm. Functional magnetic resonance imaging found
      frontal, temporal, and parietal cortex activation during an attention task with
      greater activation of the left superior-temporal and left supramarginal gyri
      associated with better performance. Individual differences in early cumulative
      risk are related to patterns of brain activation such that medical risk is
      related to left parietal cortex activation and environmental risk is related to
      temporal lobe activation. The findings suggest that early risk is related to less
      mature patterns of brain activation, including reduced efficiency of processing
      and responding to stimuli.

PMID- 16611180
TI  - The role of negative priming in preschoolers' flexible rule use on the
      dimensional change card sort task.
AB  - Four experiments examined the development of negative priming (NP) in 3-5-year
      old children using as a measure of children's executive function (EF) the
      dimensional change card sort (DCCS) task. In the NP version of the DCCS, the
      values of the sorting dimension that is relevant during the preswitch phase are
      removed during the postswitch phase. The experiments showed that the NP effect
      observed in the DCCS decreased during the preschool years, and they clarified the
      circumstances in which NP occurs. Taken together, the findings suggest that the
      development of EF in early childhood consists in part in disinhibiting attention
      to information that has previously been suppressed.

PMID- 16611181
TI  - Children's thinking about counterfactuals and future hypotheticals as
      possibilities.
AB  - Two experiments explored whether children's correct answers to counterfactual and
      future hypothetical questions were based on an understanding of possibilities.
      Children played a game in which a toy mouse could run down either 1 of 2 slides.
      Children found it difficult to mark physically both possible outcomes, compared
      to reporting a single hypothetical future event, "What if next time he goes the
      other way ..." (Experiment 1: 3-4-year-olds and 4-5-year-olds), or a single
      counterfactual event, "What if he had gone the other way ...?" (Experiment 2: 3-4
      year-olds and 5-6-year-olds). An open counterfactual question, "Could he have
      gone anywhere else?," which required thinking about the counterfactual as an
      alternative possibility, was also relatively difficult.

PMID- 16611182
TI  - God does not play dice: causal determinism and preschoolers' causal inferences.
AB  - Three studies investigated children's belief in causal determinism. If children
      are determinists, they should infer unobserved causes whenever observed causes
      appear to act stochastically. In Experiment 1, 4-year-olds saw a stochastic
      generative cause and inferred the existence of an unobserved inhibitory cause.
      Children traded off inferences about the presence of unobserved inhibitory causes
      and the absence of unobserved generative causes. In Experiment 2, 4-year-olds
      used the pattern of indeterminacy to decide whether unobserved variables were
      generative or inhibitory. Experiment 3 suggested that children (4 years old)
      resist believing that direct causes can act stochastically, although they accept
      that events can be stochastically associated. Children's deterministic
      assumptions seem to support inferences not obtainable from other cues.

PMID- 16611183
TI  - Children's beliefs about everyday reasoning.
AB  - Two studies investigated children's metacognition about everyday reasoning,
      assessing how they distinguish reasoning from nonreasoning and "good" reasoning
      from "bad." In Study 1, 80 1st graders (6-7 years), 3rd graders (8-9 years), 5th
      graders (10-11 years), and adults (18+ years) evaluated scenarios where people
      (a) used reasoning, (b) solved problems with nonreasoning approaches, or (c)
      reacted appropriately but automatically to events. All age groups distinguished
      reasoning from type (b) nonreasoning cases, but age-related improvement occurred
      for type (c) cases. Study 2 tested 160 1st, 3rd, 5th graders' and adults'
      evaluation of good and bad reasoning processes, finding 2 developmental changes:
      initial improvement in discriminating thinking processes by 3rd grade, and
      emergence of an adult-like, process-focused (vs. outcome-focused) concept of
      thinking quality by 5th grade.

PMID- 16611184
TI  - Mother and infant talk about mental states relates to desire language and emotion
      understanding.
AB  - This study assessed the relation between mother mental state language and child
      desire language and emotion understanding in 15-24-month-olds. At both time
      points, mothers described pictures to their infants and mother talk was coded for
      mental and nonmental state language. Children were administered 2 emotion
      understanding tasks and their mental and nonmental state vocabulary levels were
      obtained via parental report. The results demonstrated that mother use of desire
      language with 15-month-old children uniquely predicted a child's later mental
      state language and emotion task performance, even after accounting for
      potentially confounding variables. In addition, mothers' tendency to refer to the
      child's over others' desires was the more consistent correlate of mental state
      language and emotion understanding.

PMID- 16611185
TI  - Self in learning: Chinese adolescents' goals and sense of agency.
AB  - This study examined goals and agency as the 2 core aspects of self in learning
      among Chinese adolescents. A sample of 259 adolescents aged 12-19 responded to
      open-ended probes about themselves. Counter to the common view that Chinese
      selves are predominantly social, adolescents expressed many more individual than
      social goals and agency. Moreover, older adolescents showed overall more goals
      and agency than younger adolescents. However, their specific goals did not differ
      by age. Regarding agency, older adolescents articulated more of the so-called
      "learning virtues." Yet their social agency did not differ by age. We interpret
      these findings as in reference to the Confucian learning tradition, the existing
      research on goals and agency, and self in culture from a domain-specific
      perspective.

PMID- 16611186
TI  - Efficacy of repeated high-dose hepatitis B vaccine (80 microg) in patients with
      chronic liver disease.
AB  - Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B
      (HBV) vaccine given as sequential 20 microg IM shots because of an overall
      impaired immune response. Many of these patients go on to liver transplantation
      and are at risk of acquiring recurrent or de novo HBV infection. To evaluate the
      efficacy and safety of high-dose (80 microg) IM HBV vaccination in patients with
      CLD who had previously failed to respond to a standard three-dose schedule of 40
      microg IM vaccine given monthly. A retrospective review was undertaken at our
      institution of 79 patients with CLD who were treated with high-dose (80 microg)
      HBV vaccinations. All had previously failed a three-dose course of 40 microg HBV
      vaccine. An HBV vaccine response was defined as an anti-HBs titer greater than
      100 mIU/ml. Liver enzymes, creatinine, age, prothrombin time, total vaccine dose,
      and MELD score were recorded. No adverse events were reported. Seventy-two per
      cent (57/79) of the subjects had an adequate response after receiving a mean
      total dose of 220 mug vaccine (range 80-800 microg). Twenty-eight per cent
      (22/79) of the subjects did not respond after receiving a mean total dose of 420
      microg vaccine (range 240-720 microg). Non-responders had more severe hepatic
      disease defined as a higher mean total bilirubin level (p = 0.003) and a lower
      mean albumin level (p < 0.05). Age, prothrombin time, MELD score, and creatinine
      were not statistically significant between the responders and non-responders.
      Repeated high-dose (80 microg) HBV vaccination, in patients who do not respond to
      standard HBV vaccine doses, is safe and effective in the majority of patients
      with CLD.

PMID- 16611187
TI  - A rapid real-time PCR assay for determination of hepatitis C virus genotypes 1, 2
      and 3a.
AB  - The genotypes of hepatitis C virus (HCV) in serum of patients have been described
      as independent predictors of success of antiviral therapy. Therefore, different
      antiviral regimens have been proposed depending on the infecting HCV genotype.
      HCV strain is usually determined by polymerase chain reaction (PCR) amplification
      of genome followed by sequencing or by line-probe assays. We report a new one
      step real-time PCR assay for genotyping of HCV strains that are prevalent in
      patients in Norway. HCV types 1, 2 and 3a were genotyped unambiguously in 37
      patient serum samples with 100% correlation to genotyping by nucleotide sequence
      analysis and line-probe assays. Genotyping could also be confirmed against an HCV
      genotype panel from the National Institute for Biological Standards and Control.
      This assay does not require manipulation of amplified PCR products, it involves
      very little hands on and analysis time. This assay can be used for rapid
      genotyping of HCV-RNA in infected patients to aid physicians decide suitability
      of patients for treatment and subsequent length of treatment.

PMID- 16611188
TI  - Modulation of the anti-inflammatory interleukin 10 and of proapoptotic IL-18 in
      patients with chronic hepatitis C treated with interferon alpha and ribavirin.
AB  - The aim of this work was to analyse apoptosis rate, measured by the serum levels
      of proapoptotic interleukin (IL)-18 and of soluble Fas (sFas), as well as of anti
      inflammatory IL-10, in patients with chronic hepatitis C, at baseline and after
      treatment with interferon alpha and ribavirin. Twenty-seven patients with biopsy
      proven chronic hepatitis C were studied, at baseline and after treatment with
      interferon alpha (21 cases) or pegylated interferon (6 cases) plus ribavirin. A
      group of 15 healthy sex- and age-matched individuals was selected as control.
      Serum concentrations of sFas, IL-10 and IL-18 were determined by ELISA in
      sandwich. The relationship of these molecules to necro-inflammatory and fibrotic
      activity was evaluated. Evolution of the serum concentrations of these molecules
      was analysed after treatment. Significantly increased serum concentrations of
      sFas were detected in patients with chronic hepatitis, compared with controls.
      Levels of this molecule were significantly correlated with necroinflammatory
      activity. Likewise, concentrations of IL-10 were significantly increased in the
      group of patients, compared with controls. Treatment with interferon and
      ribavirin induced a significant decrease of IL-18 concentration independently of
      the viral response. In contrast, levels of sFas decreased only in those patients
      with sustained response to therapy. Finally, baseline levels of IL-10 were
      significantly increased in patients without response to treatment, compared with
      those with sustained response, but the concentration did not change with the
      treatment. Increased serum levels of IL-10 are a negative prognostic marker of
      response to hepatitis C treatment. A significant decrease of apoptotic rate, as
      determined by sFas, can be expected in patients with a response to therapy.

PMID- 16611189
TI  - Comparison of hepatitis C treatment patterns in patients with and without
      psychiatric and/or substance use disorders.
AB  - Hepatitis C virus (HCV) infection is more frequent in veterans than in
      nonveterans. Up to 85% of HCV-infected veterans have psychiatric and/or substance
      use (SU) co-morbidities which, prior to the 2002 NIH Consensus Conference, were
      considered relative contraindications to antiviral therapy, assuming a poor
      adherence. With the objective of evaluating the validity of this assumption, we
      compared eligibility, completion and response to antiviral therapy in HCV
      infected veterans with and without these comorbidities. Veterans who were anti
      HCV-positive and had been seen at least once in the liver clinic (between October
      1999 and June 2002) were identified through the CT-VAHCS database. Records were
      reviewed for patient demographics and status of liver disease, assessment of
      treatment eligibility, type of therapy, completion of therapy and virological
      response. Patients with active mental illness (MI) or SU were compared with those
      without these comorbidities (controls). Of 697 anti-HCV-positive-patients, 647
      HCV-RNA-positive patients were included, 294 with MI/SA and 353 controls. Patient
      demographics, viral and liver disease characteristics were comparable between
      groups. Patients with MI/SA were considered ineligible for therapy more
      frequently (53%vs 39%, P < 0.001) and were treated less frequently (21%vs 28%, P
      = 0.03) than controls. However, completion of therapy (72%vs 59%) and sustained
      virological response (SVR) (20%vs 25%) did not differ significantly between
      groups. HCV-infected veterans with MI/SA are being offered therapy and treated
      less often than those without such co-morbidities, however therapy completion and
      SVR rates are similar, challenging the perception that adherence is poorer in
      this patient population.

PMID- 16611190
TI  - Black patients with chronic hepatitis C have a lower sustained viral response
      rate than non-Blacks with genotype 1, but the same with genotypes 2/3, and this
      is not explained by more frequent dose reductions of interferon and ribavirin*.
AB  - In previous hepatitis C virus (HCV) treatment studies, Black patients not only
      had a lower sustained viral response (SVR) rate to interferon and ribavirin (RBV)
      than non-Black patients but also a higher frequency of HCV genotype 1 (GT-1)
      infection. The aim of this community-based study was to determine whether Black
      patients have a lower SVR rate independent of genotype. We prospectively enrolled
      785 patients (24.8% Black, 71.5% White, 3.7% others) who received interferon
      alpha-2b 3 MU three times weekly + RBV 1000-1200 mg/day for 24 weeks (GT-2/3) or
      48 weeks (GT-1). Black patients were more commonly infected with GT-1 (86.8%vs
      64.8%, P < 0.001) and less frequently had an SVR compared with non-Black patients
      (8.4%vs 21.6%, P < 0.001). Within GT-1, Black patients had a lower SVR rate than
      non-Black patients (6.1%vs 14.1%, P = 0.004) but not within GT-2/3 (50.0%vs
      36.5%, P = 0.47). Black patients had lower baseline haemoglobin levels (14.8 vs
      15.3 g/dL, P < 0.001) and neutrophil counts (2900 vs 4100/mm(3), P < 0.001) and
      required more frequent dose reductions of RBV (29.8%vs 18.5%, P < 0.001) and
      interferon (4.7%vs 1.6%, P = 0.012). However, dose reductions were not associated
      with lower SVR rates while early treatment discontinuations were (2.9%vs 25.7%, P
      < 0.001). Independent predictors of SVR were GT-1 [odds ratio (OR) 0.33; 95%
      confidence interval (CI) 0.20-0.55; P < 0.001], Black race (OR 0.45; 95% CI 0.22
      0.93; P = 0.030), and advanced fibrosis, stages 3 + 4 (OR 0.53; 95% CI 0.31-0.92;
      P = 0.023). In conclusion, Black patients infected with HCV GT-1 (but not GT-2/3)
      have a lower SVR rate than non-Black patients. This is not explained by their
      lower baseline haemoglobin levels and neutrophil counts that lead to higher rates
      of ribavirin and interferon dose reductions.

PMID- 16611191
TI  - Switching to adefovir monotherapy after emergence of lamivudine-resistant
      mutations in patients with liver cirrhosis.
AB  - Switching to adefovir (ADV) monotherapy is effective in patients with lamivudine
      (LAM)-resistant hepatitis B virus (HBV) mutations (rtM204 I/V). However, it was
      recommended to continue LAM therapy for months after starting ADV therapy for
      safety concern. The safety and efficacy of switching to ADV monotherapy was
      examined in compensated and decompensated patients with liver cirrhosis. The
      clinical, biochemical and virological responses were compared between ADV
      monotherapy in 18 cirrhotic patients and ADV add-on LAM therapy in 10 comparable
      cirrhotic patients with LAM-resistant rtM204 I/V. After switching to ADV
      monotherapy, Child-Pugh's score, serum alanine aminotransferase (ALT), bilirubin,
      albumin and HBV DNA levels improved significantly (P < 0.01). Serum HBV DNA
      response, defined as HBV DNA decreased to below 10(5) copies/mL or > or =2
      log(10) reduction form baseline, was achieved in all patients. A transient ALT
      flare without concurrent changes in serum bilirubin or prothrombin time was
      observed in only two patients (11%). The efficacy and safety profile was similar
      to those with ADV add-on LAM therapy. In conclusion, switching to ADV monotherapy
      after emergence of LAM-resistant rtM204 I/V is effective and safe in cirrhotic
      patients, even in those with hepatic decompensation. To stop LAM and switch to
      ADV in patients with breakthrough is a reasonably safe and cost-effective
      approach.

PMID- 16611192
TI  - Safety and efficacy of lamivudine in patients with severe acute or fulminant
      hepatitis B, a multicenter experience.
AB  - Acute hepatitis B progresses to liver failure with the need of liver
      transplantation in about 1% of cases. We treated patients with severe acute or
      fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus
      (HBV) reinfection after potential liver transplantation. Since September 2000, 17
      patients with severe acute or fulminant HBV infection were treated with 100 or
      150 mg lamivudine daily once we had evidence for a severe course as indicated by
      an INR >2.0. These were compared to a historic control from our unit and to
      external patients. Fourteen of the 17 patients (82.4%) survived with full
      recovery without liver transplantation. All these 14 individuals cleared HBsAg on
      lamivudine within less than 6 months. Twelve patients recovered quickly as
      indicated by a normalized prothrombin time within 1 week while two patients had a
      more prolonged course. None of the patients showed an adverse event. Three
      patients requiring transplantation despite lamivudine therapy had more advanced
      disease on admission, of whom one had additionally ingested paracetamol
      (acetaminophen) while the second was already HBV-DNA negative by polymerase chain
      reaction on admission. The lamivudine treated patients had significant higher
      frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the
      historic control (P < 0.001). Similar data were derived from external centres
      using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute
      or fulminant hepatitis B, leading to fast recovery with the potential to prevent
      liver failure and liver transplantation when administered early enough.

PMID- 16611193
TI  - Clinical pathways for patients with newly diagnosed hepatitis C - what actually
      happens.
AB  - Management of hepatitis C virus (HCV)-infected individuals requires referral to
      specialist care. To determine whether patients newly diagnosed as anti-HCV
      positive are appropriately referred for further investigation and management, and
      if not, to determine why not. We studied patients tested for antibodies to HCV by
      Nottingham Public Health Laboratory in a 2-year period (2000-2002). The progress
      of newly diagnosed anti-HCV positive patients into specialist clinics for further
      management was documented. For patients not referred for specialist care, a
      questionnaire was sent to the clinician requesting the initial anti-HCV test, to
      identify reasons for nonreferral. Eleven thousand one hundred and seventy-seven
      patients were tested for anti-HCV. Two hundred and fifty-six (2.3%) were newly
      diagnosed as being anti-HCV positive. Two per cent of samples sent from primary
      care were anti-HCV positive, compared to 18.8, 18.9 and 1.3% sent from prison,
      drug and alcohol units, and secondary care, respectively. About 64.3% of positive
      patients diagnosed in primary care were referred to specialist care, compared to
      18.4, 42.4 and 62.6% of patients diagnosed in the other three settings. One
      hundred and twenty-five (49%) newly diagnosed patients were referred
      appropriately for further management. 68 of these attended clinic, 45 underwent
      liver biopsy and 26 (10%) began treatment. One hundred and thirty-one patients
      (51%) were not referred. In 54 cases, there was no evidence that the anti-HCV
      positive result reached the patient. In 15, referral was considered but rejected,
      and 20 patients were referred to non-HCV-specialists (their general practitioners
      or to genito-urinary medicine). Hence less than 50% of newly diagnosed anti-HCV
      positive patients are referred to an appropriate clinic for further investigation
      and management. Reasons for this are multifarious and complex, reflecting both
      systems failure and patient choice. Unless these are understood and addressed,
      the Department of Health Hepatitis C Strategy (2002) and Action Plan for England
      (2004) will fail to achieve their intended objectives.

PMID- 16611194
TI  - Is hepatitis C virus a risk factor for thyroid autoimmunity?
AB  - The role of hepatitis C virus (HCV) in inducing thyroid autoimmunity is still
      under discussion and to assess the prevalence of thyroid autoantibodies and
      thyroid disease in the general population and to analyse the role of HCV in
      inducing thyroid autoimmunity. We studied 697 subjects residing in Arsita (a
      small town in central Italy). Thyroid autoantibodies and nonorgan-specific
      autoantibodies (NOSAs) were tested in each subject, who were also screened for
      anti-HCV antibodies; all subjects found positive to HCV-RNA were considered as
      being HCV-infected. Thyroid function tests were performed in all subjects
      positive for thyroid autoantibody. Seventy-one subjects were found HCV-positive;
      four of these (5.6%) were positive for at least one thyroid autoantibody, as
      opposed to 7 (4.9%) of the 142 sex- and age-matched controls of the same
      population (P = n.s.). Thyroid dysfunction was found in 2/4 HCV-positive, and in
      1/7 HCV-negative subjects with thyroid autoantibodies (P = n.s.). NOSAs were
      significantly more common in HCV-positive than in HCV-negative subjects (P <
      0.0001). Hence HCV per se is not responsible for thyroid autoimmune dysfunction,
      whereas HCV does seem to induce NOSAs. It should be taken into account, however,
      that the phenotypic expression of autoimmune diseases is obviously influenced by
      a number of risk factors, including genetic predisposition, female sex and
      infectious agents, that could trigger the onset of the disease.

PMID- 16611196
TI  - Current controversies in pharmacoepidemiology.

PMID- 16611197
TI  - Comparison of dynamic treatment regimes via inverse probability weighting.
AB  - Appropriate analysis of observational data is our best chance to obtain answers
      to many questions that involve dynamic treatment regimes. This paper describes a
      simple method to compare dynamic treatment regimes by artificially censoring
      subjects and then using inverse probability weighting (IPW) to adjust for any
      selection bias introduced by the artificial censoring. The basic strategy can be
      summarized in four steps: 1) define two regimes of interest, 2) artificially
      censor individuals when they stop following one of the regimes of interest, 3)
      estimate inverse probability weights to adjust for the potential selection bias
      introduced by censoring in the previous step, 4) compare the survival of the
      uncensored individuals under each regime of interest by fitting an inverse
      probability weighted Cox proportional hazards model with the dichotomous regime
      indicator and the baseline confounders as covariates. In the absence of model
      misspecification, the method is valid provided data are available on all time
      varying and baseline joint predictors of survival and regime discontinuation. We
      present an application of the method to compare the AIDS-free survival under two
      dynamic treatment regimes in a large prospective study of HIV-infected patients.
      The paper concludes by discussing the relative advantages and disadvantages of
      censoring/IPW versus g-estimation of nested structural models to compare dynamic
      regimes.

PMID- 16611195
TI  - A prospective study of the evolution of lamivudine resistance mutations in
      patients with chronic hepatitis B treated with lamivudine.
AB  - Lamivudine resistance has been described in subjects with chronic hepatitis B
      infections, associated with mutations in the viral polymerase gene. The objective
      of this study was to estimate the emergence rate of lamivudine-resistant viral
      strains and their consequences over a 2-year period. We evaluated 283 lamivudine
      naive subjects with chronic hepatitis B. Clinical and virological features were
      assessed at inclusion and every 6 months thereafter. Viral DNA was characterized
      using polymerase chain reaction (PCR)-based sequencing. Potential risk factors
      for the emergence of lamivudine resistance mutations were assessed using logistic
      regression analysis. The annualized incidence rate for viral polymerase mutations
      was 22%. The only independent risk factor identified was high viral load, at
      inclusion. Detectable viral DNA and elevated transaminases were more frequent in
      subjects harbouring mutant viral strains, and these underwent a lower rate of
      hepatitis B e seroconversion. All subjects responded favourably to treatment,
      with no difference in symptoms between the two groups. This prospective cohort
      study identified lamivudine-resistant mutations emerging in 22% of subjects,
      yearly, which were apparently not associated with clinical aggravation over the
      study period.

PMID- 16611198
TI  - Measuring prescribing improvements in pragmatic trials of educational tools for
      general practitioners.
AB  - Randomized pragmatic trials of drugs, physician education and drug policies are
      needed to improve pharmacosurveillance and cost-effectiveness of prescribing.
      Since 1994, we have developed and tested methods for low-cost education and
      policy trials to improve prescribing in primary care in Canada. We review
      methodology for using drug claims and other health services data to evaluate
      prescribing improvement programs and policies. We apply the lessons to a proposed
      trial of physician education tools (PET) for quality improvement of prescribing.
      Design issues for the trial include defining the potential programme in causal
      terms using counterfactuals, narrowing the denominator to the population
      affected, excluding noise from the numerator, calculating the prescribing
      preference, adjusting for baseline differences, controlling for modifiers and
      confounders, accounting for uncertainty when measuring impacts, and grouping
      practices for feedback and recognition. Data from a randomized trial of academic
      detailing illustrate measurement challenges. A decade of progress on methods for
      evaluating prescribing improvement programs with drug claims data has enabled
      planning of routine randomized pragmatic trials of education and policies in
      primary care in Canada.

PMID- 16611199
TI  - Indications for propensity scores and review of their use in
      pharmacoepidemiology.
AB  - Use of propensity scores to identify and control for confounding in observational
      studies that relate medications to outcomes has increased substantially in recent
      years. However, it remains unclear whether, and if so when, use of propensity
      scores provides estimates of drug effects that are less biased than those
      obtained from conventional multivariate models. In the great majority of
      published studies that have used both approaches, estimated effects from
      propensity score and regression methods have been similar. Simulation studies
      further suggest comparable performance of the two approaches in many settings. We
      discuss five reasons that favour use of propensity scores: the value of focus on
      indications for drug use; optimal matching strategies from alternative designs;
      improved control of confounding with scarce outcomes; ability to identify
      interactions between propensity of treatment and drug effects on outcomes; and
      correction for unobserved confounders via propensity score calibration. We
      describe alternative approaches to estimate and implement propensity scores and
      the limitations of the C-statistic for evaluation. Use of propensity scores will
      not correct biases from unmeasured confounders, but can aid in understanding
      determinants of drug use and lead to improved estimates of drug effects in some
      settings.

PMID- 16611200
TI  - Templates for analysis of individual-level prescription data.
AB  - The advent of large population-based prescription databases has enabled us to
      study drug use with the individual user as our unit of analysis. This review
      presents three non-specific analytic templates that may be applied to individual
      level prescription data. The ratio of prevalence odds to incidence rate can
      estimate the average duration for drug use. Limitations and pitfalls are
      discussed. Although it should be cautiously interpreted, it provides a reasonable
      ranking of drugs with respect to their retention in users. The Lorenz curve is an
      analytic tool to express skewness in drug use. It shows the proportion of drug
      use that is accounted for by percentiles of drug users, ranked according to their
      volume of drug intake. It may express the extent of heavy users as well as
      sporadic small-volume users and may, for example, be used to screen for an
      unsuspected abuse potential of a drug. The waiting-time distribution is a
      frequency distribution of first occurrences of drug use within a time-window. It
      forms the basis for a theoretical model for robust estimates of prevalence and
      incidence rate. On an intuitive level, it displays visual correlates of
      epidemiological prescribing parameters such as period prevalence, point
      prevalence, incidence rate, duration, prescription renewal rate, relapse of
      treatments and seasonality. Each measure may be incorporated into an integral
      matrix that reflects various traits in utilization of every drug or drug class,
      thereby possibly finding abnormalities that suggest sub-optimal prescribing.

PMID- 16611201
TI  - Non-steroidal antiinflammatory drugs and the risk of acute myocardial infarction.
AB  - Whether non-aspirin non-steroidal antiinflammatory drugs (NSAIDs) affect the risk
      of myocardial infarction is unclear. Also, it is unknown whether the effect
      varies by individual NSAIDs. To summarize the evidence from published
      observational studies on the risk of myocardial infarction associated with both
      traditional NSAIDs (tNSAIDs) and selective inhibitors of cyclooxygenase-2
      (Coxibs), the authors conducted a systematic review of cohort and case-control
      studies on NSAIDs and myocardial infarction published between 2000 and 2005.
      Sixteen original studies were selected according to predefined criteria. Two
      researchers independently extracted the data on individual study characteristics
      and results. The authors calculated pooled relative risk (RR) estimates of
      myocardial infarction for specific NSAIDs compared with no NSAID use, tested the
      heterogeneity of effects, and evaluated potential reasons for heterogeneity. The
      pooled RR of myocardial infarction was 0.98 (95% confidence interval (CI): 0.92
      1.05) for naproxen, 1.07 (95% CI: 1.02-1.12) for ibuprofen, 1.44 (95% CI: 1.32
      1.56) for diclofenac, 0.96 (95% CI: 0.90-1.02) for celecoxib, and 1.26 (95% CI:
      1.17-1.36) for rofecoxib (all doses). The pooled RR for rofecoxib at doses >25
      mg/day was 1.78 (95% CI: 1.36-2.34), and 1.18 (95% CI: 1.07-1.31) for doses < or
      =25 mg/day. The RR associated with naproxen was 0.83 (95% CI: 0.72-0.90) among
      non-users of low-dose aspirin. The RR associated with rofecoxib (all doses) was
      1.39 (95% CI: 1.25-1.54) among subjects without a history of myocardial
      infarction. The risk of myocardial infarction varies with individual NSAIDs. An
      increased risk was observed for diclofenac and rofecoxib, the latter one with a
      clear dose-response trend. There was a suggestion of a small increased risk with
      ibuprofen. Also, data suggest a small reduced risk for naproxen present only in
      non-users of aspirin, mainly people free of clinically apparent vascular disease.

PMID- 16611202
TI  - Is there an interaction between the cardiovascular protective effects of low-dose
      aspirin and ibuprofen?
AB  - Laboratory studies and studies in normal volunteers have suggested a possible
      adverse interaction between aspirin and ibuprofen. It is thought that ibuprofen
      prevents aspirin from gaining access to platelet cyclooxygenase. Following the
      publication of these studies, a number of observational and other studies have
      been published. We review these studies identified by structured searching of
      Medline and Pubmed databases. We conclude that on the balance of probabilities
      that ibuprofen is more likely to interact with aspirin than not. This interaction
      is more likely in those who take ibuprofen chronically and is more important in
      those at high cardiovascular risk. Thus, a reasonable strategy might be to advise
      aspirin takers to avoid chronic ibuprofen.

PMID- 16611203
TI  - Chemoprevention in gastrointestinal cancers: current status.
AB  - Chemoprevention, pharmacological intervention for disease prevention, aims to
      intervene in pathways that lead to clinical disease before the disease occurs.
      Cancer chemoprevention is a relatively new field, but for gastrointestinal
      cancers, clinical trials have highlighted the chemopreventive potential of
      several agents. For colorectal neoplasia, trials with aspirin and other non
      steroidal anti-inflammatory drugs (NSAIDS) and calcium have demonstrated the most
      significant reductions of risk. In observational studies, NSAIDs also
      consistently appear to protect against oesophageal and gastric cancer. Calcium,
      and perhaps vitamin D, are also promising and have the advantage of being
      inexpensive, safe interventions. For the prevention of oesophageal cancer,
      antitumour-B and retinamide have provided hopeful results, although it is not
      clear that these findings can be extrapolated from the study populations in Asia
      to western countries. Evidence from China suggests that a combination of beta
      carotene, alpha-tocopherol and selenium may protect against oesophageal cancer,
      but the relative importance of each agent is unclear, and, again, their effects
      in other populations has not yet been assessed. Mass immunization against
      hepatitis B seems to be the most effective means of reducing the incidence of
      hepatocellular cancer worldwide. In addition, treatment with interferon alpha in
      patients chronically infected with hepatitis C virus shows considerable promise,
      given the increasing prevalence of hepatitis C virus carriage in recent years. TJ
      9, polyprenoic acid and anti-aflatoxin compounds are also possible avenues that
      deserve future research.

PMID- 16611204
TI  - The risk of breast, endometrial and ovarian cancer in users of hormonal
      preparations.
AB  - Because endogenous hormones play a major role in the risk of breast, endometrial
      and ovarian cancer, the impact on risk of oral contraceptives and of hormonal
      therapy given at about the time of menopause has been a major concern. Numerous
      studies provide insight into whether risk is increased or decreased in
      association with use of these preparations. Oral contraceptives present a
      chemopreventive opportunity for endometrial cancer and ovarian cancer as risk is
      dramatically lower among women who have used these preparations than among those
      who have not. Balanced against this is the potential for risk of breast cancer to
      be increased with oral contraceptive use. A pooled analysis of studies conducted
      through the early 1990s found that only current or recent users were at higher
      risk of breast cancer, but two more recent studies provide conflicting results
      with one showing no impact of oral contraceptives on risk of any group of women
      and the other showing an increase in risk with use. Among women participating in
      observational studies who are current or recent users of oestrogen therapy and
      who have relatively long durations of use, risk of breast cancer is modestly
      elevated; results from the Women's Health Initiative trial, based on a relatively
      short duration of oestrogen use are consistent with these observations. Oestrogen
      therapy increases endometrial cancer risk dramatically. It may also increase the
      risk of ovarian cancer; however more study of this issue is needed as the
      literature is inconsistent. Combined oestrogen and progestin therapy increases
      breast cancer risk by as much as 10% per year of use. Endometrial cancer risk is
      not elevated when combined therapy is given in a cyclic manner with progestin
      administered only part of the time and it is reduced when both oestrogen and
      progestin are administered on a daily basis. As with oestrogen therapy, the
      impact of combined therapy on ovarian cancer risk is uncertain.

PMID- 16611205
TI  - Upper gastrointestinal complications among users of paracetamol.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with upper
      gastrointestinal complications such as bleeding or perforation. Paracetamol has
      been traditionally considered a safer alternative to NSAIDs. In a previous case
      control study we found that paracetamol at high doses increased the risk of upper
      gastrointestinal complications. We proposed to review all studies addressing the
      association between paracetamol and upper gastrointestinal complications and
      placed our results in the context of existing literature. We conducted a nested
      case-control study using the United Kingdom General Practice Research Database
      during the period between April 1993 and October 1998. Then we performed a
      systematic review of the literature indexed in MEDLINE published between 1980 and
      2004. We identified a total of twelve studies that assessed the association
      between paracetamol and upper gastrointestinal complications. We used a fixed
      effects model to calculate a summary estimate of these studies. In the nested
      case control study, use of paracetamol was associated with a small elevated risk
      of upper gastrointestinal complications (relative risk (RR), 1.3; 95% confidence
      interval (CI), 1.1-1.5). The RR was 3.6 (95% CI, 2.6-5.1) among paracetamol users
      of more than 2 g daily, whereas smaller doses did not increase the risk. Among
      the twelve studies identified in the systematic review, estimates ranged from 0.2
      through 2.0 with a summary estimate of 1.3 (95% CI, 1.2-1.5). Our findings
      indicate that use of paracetamol at the doses most commonly used confer little or
      no increased risk of upper gastrointestinal complications. More data are needed
      to confirm or refute the suggestion that high-dose paracetamol is associated with
      an increased risk of upper gastrointestinal complications of the same magnitude
      as the one observed with traditional NSAIDs.

PMID- 16611206
TI  - Antidepressants and risk of upper gastrointestinal bleeding.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are nowadays the most widely used
      antidepressants in the world, mainly because they have a better adverse reaction
      profile and a higher safety margin in overdoses, when compared to other
      antidepressants. These drugs recently have been the target of important debates
      concerning safety issues, among them the possibility that they may increase the
      risk of bleeding. Over the 1990s, an increasing number of individual cases of
      bleeding disorders were reported in the literature and to the pharmacovigilance
      programmes which prompted several epidemiological and pharmacological studies. In
      this review we have examined all available data. The whole evidence supports the
      hypothesis that antidepressants with a relevant blockade action on serotonin
      reuptake mechanism increase the risk of bleeding. Such disorders may have
      different degrees of severity and may be located anywhere in the body. The
      epidemiological evidence is, however, more robust for upper gastrointestinal
      bleeding. It has been estimated that upper gastrointestinal bleeding may occur at
      a frequency ranging from 1 in 100 to 1 in 1,000 patient-years of exposure to high
      affinity drugs (the SSRIs), with the very old patients being in the highest part
      of the range. The increased risk may be of particular relevance when the SSRIs
      are associated with NSAIDs as well as low-dose aspirin.

PMID- 16611207
TI  - Use of health care databases in pharmacoepidemiology.
AB  - Pharmacoepidemiology is the study of the use and effects of medications in
      populations. Large health care databases are often used to address research
      questions within pharmacoepidemiology. This paper briefly describes the kinds of
      research questions that can be addressed using pharmacoepidemiology databases,
      provides an overview of pharmacoepidemiologic databases, describes some
      differences between medical records and administrative databases, discusses
      factors that should be considered when choosing a database for a particular
      study, and considers what the future holds.

PMID- 16611208
TI  - Is it possible to measure prescribing quality using only prescription data?
AB  - A large number of prescribing quality indicators based on register data have been
      proposed and many are used routinely in quality management. Often the content and
      face validity of indicators have been assessed by consensus methods, but studies
      analysing other validity aspects are scarce. Prescription data are frequently
      used for indicators, but they do not provide any direct information about disease
      and patient factors important for judging the quality of prescribing. If register
      based proxies for diagnoses, disease severity or risk factors are employed,
      validation is essential. The concurrent validity of indicators should be assessed
      by comparing to a "gold standard" quality assessment at the patient level using
      all available clinical information. The validity of frequently used quality
      indicators of asthma treatment has been questioned and should be further
      investigated. NSAID prescribing indicators are currently under evaluation. In the
      future, detailed clinical information from practice databases and computerised
      hospital records will be an important data source for indicators and for
      validation studies. Furthermore, the statistical and epidemiological properties
      of prescribing quality indicators need more attention.

PMID- 16611209
TI  - Making the most of spontaneous adverse drug reaction reporting.
AB  - The primary purpose of spontaneous adverse drug reaction reporting is to provide
      early warnings or "signals" of previously unrecognized drug toxicity. The method
      was developed in the 1960s in response to the thalidomide tragedy and is now well
      established throughout the developed world. Health professionals are the key
      original source of reports, the value of patient reporting is yet unclear.
      Electronic transmission of all reports is likely to become the norm within a few
      years. This is well-advanced between pharmaceutical companies and regulatory
      authorities but still in its infancy for health professionals in many parts of
      the world. Considered globally, the process may be inefficient and movement
      towards centralization of databases with appropriate access controls is logical.
      Alternative methods for capturing clinical suspicions of adverse drug reactions
      should be investigated and could provide more systematic data. However much it
      can be improved, spontaneous adverse drug reaction reporting is unlikely to
      identify all important unrecognized drug safety hazards. Complementary approaches
      therefore still need to be identified and developed.

PMID- 16611210
TI  - Data mining in spontaneous reports.
AB  - The increasing size of spontaneous report data sets and the increasing capability
      for screening such data due to increases in computational power has led to a
      recent increase in interest and use of data mining on such data. While data
      mining plays an important role in the analysis of spontaneous reports, there is
      general debate on how and when data mining should be best performed. While the
      cornerstone principles for data mining of spontaneous reports have been in place
      since the 1960s, several significant changes have occurred to make their use
      widespread. Superficially the Bayesian methods seem unnecessarily complex,
      particularly given the nature of the data, but in practice implementation in
      Bayesian framework gives clear benefits. There are difficulties evaluating the
      performance of the methods, but they work and save resources in managing large
      data sets. The use of neural networks allows more sophisticated pattern
      recognition to be performed.

PMID- 16611212
TI  - Chemical biology and drug design: three-dimensional, dynamic, and mechanistic
      nature of two multidisciplinary fields.

PMID- 16611213
TI  - Substituted 1,4-benzodiazepine-2,5-diones as alpha-helix mimetic antagonists of
      the HDM2-p53 protein-protein interaction.
AB  - Small molecule antagonists of protein-protein interactions represent a particular
      challenge for pharmaceutical discovery. One approach to finding molecules that
      can disrupt these interactions is to seek mimics of common protein structure
      motifs. We present an analysis of how molecules based on the 1,4-benzodiazepine
      2,5-dione scaffold serve to mimic the side-chains presented by the hydrophobic
      face of two turns of an alpha-helix derived from the tumor suppressor protein
      p53, and thus antagonize the HDM2-p53 protein-protein binding interaction.

PMID- 16611214
TI  - Synthesis and molecular modelling of novel substituted-4,5-dihydro-(1H)-pyrazole
      derivatives as potent and highly selective monoamine oxidase-A inhibitors.
AB  - This report describes novel pyrazoline derivatives investigated for their ability
      to selectively inhibit the activity of the A and B isoforms of monoamine oxidase.
      These new synthetic compounds proved to be reversible, potent, and selective
      inhibitors of monoamine oxidase-A rather than of monoamine oxidase-B, and are
      promising candidates to further advance drug discovery efforts. The most active
      compounds show inhibitory activity on monoamine oxidase-A in the 1.0x10(-8)
      8.6x10(-9) M range. Moreover, it should be pointed out that for some compounds a
      high IC50>or=10(-9) M value is associated with a high A-selectivity (Selectivity
      Index monoamine oxidase-B/monoamine oxidase-A in the 10,000-12,500 range).
      Further insight to understand enzyme-inhibitor molecular interaction was obtained
      by docking experiments with the monoamine oxidase-A and monoamine oxidase-B
      isoforms.

PMID- 16611215
TI  - Molecular mechanism of the constitutive activation of the L250Q human
      melanocortin-4 receptor polymorphism.
AB  - The Melanocortin-4 Receptor is a G-protein coupled receptor that has been
      physiologically linked to participate in the regulation of energy homeostasis.
      The Melanocortin-4 Receptor is stimulated by endogenous melanocortin agonists
      derived from the pro-opiomelanocortin gene transcript and antagonized by the
      endogenous antagonist agouti-related protein. Central administration of
      melanocortin agonists has been demonstrated to decrease food intake and
      conversely, treatment with antagonists resulted in increased food intake.
      Deletion of the Melanocortin-4 Receptor gene from the mouse genome results in an
      obese and hyperphagic phenotype. Polymorphisms of the human Melanocortin-4
      Receptor have been found in severely obese individuals, suggesting that
      Melanocortin-4 Receptor malfunction might be involved in human obesity and
      obesity-associated diabetes. Herein, we have performed experiments to understand
      the molecular mechanisms associated with the L250Q human Melanocortin-4-Receptor
      polymorphism discovered in an extremely obese woman. This L250Q human
      Melanocortin-4-Receptor has been pharmacologically characterized to result in a
      constitutively active receptor. The fact that a constitutively active human
      Melanocortin-4-Receptor mutation was found in an obese person is a physiologic
      contradiction, as chronic activation of the human Melanocortin-4-Receptor and
      subsequently high cyclic adenosine monophosphate levels should theoretically
      result in a normal or lean phenotype. In this study, we demonstrated that agouti
      related protein acts as an inverse agonist at this constitutively active
      receptor, and we propose a mechanism by which agouti-related protein might
      contribute to the obese phenotype in the L250Q patient. In addition, using
      receptor mutagenesis, pharmacology, and computer modeling approaches, we
      investigated the molecular mechanism by which modification of the L250 residue
      results in constitutive activation of the human Melanocortin-4-Receptor.

PMID- 16611216
TI  - Phosphoinositide, phosphopeptide and pyridone interactions of the Abl SH2 domain.
AB  - Signaling proteins are localized and regulated by Src homology 2 domains which
      recognize phosphotyrosine-containing sequences. Recently, noncanonical ligands
      have been proposed for Src homology 2 domains including that of Abl and its
      breakpoint cluster region fusion, which causes chronic myelogenous leukemia.
      Here, the Abl Src homology 2 domain's binding sites and affinities for
      phosphotyrosine- and phosphoserine-containing motifs, phosphoinositides as well
      as a pyridone-based peptidomimetic inhibitor were determined using nuclear
      magnetic resonance spectroscopy in order to define their roles. The cognate Crk
      peptide ligand was bound with an affinity of 69 microM and, like the higher
      affinity peptidomimetic, engages the phosphotyrosine and +3 hydrophobic pockets
      while putative phosphoserine-containing breakpoint cluster region ligands are
      ruled out. Surprisingly, phosphatidylinositol 4, 5 bisphosphate interacts with an
      overlapping site through an electrostatic mechanism that does not appear to
      involve hydrophobic insertion into micelles. The conserved Arg36 residue in the
      FLVRES motif is required for both phosphotyrosine binding and for localization to
      phosphatidylinositol 4, 5 bisphosphate-containing liposomes, while Arg59 in the
      betaD strand is necessary for the phosphoinositide interaction. Thus the Src
      homology 2 domain of Abl, a myristoylated and membrane-localized protein, is able
      to interact directly with phosphoinositides through a multifunctional basic site
      that overlaps the phosphotyrosine pocket.

PMID- 16611217
TI  - A cell-permeable NFAT inhibitor peptide prevents pressure-overload cardiac
      hypertrophy.
AB  - The activation of the calcineurin-nuclear factor of activated T cells cascade
      during the development of pressure-overload cardiac hypertrophy has been
      previously reported in a number of studies. In addition, numerous pharmacological
      studies involving calcineurin inhibitors such as FK506 and cyclosporine A have
      now demonstrated that these agents can prevent such hypertrophic responses in the
      heart. However, little is known regarding the roles of the calcineurin downstream
      effector--nuclear factor of activated T cells. Our present study has further
      examined the roles of nuclear factor of activated T cells in pressure-overload
      cardiac hypertrophy by employing a recently developed cell-permeable nuclear
      factor of activated T cells inhibitor peptide. Rat hearts were subjected to
      pressure overload attributable by 4 weeks of aortic banding, and then treated
      with this cell-permeable nuclear factor of activated T cells inhibitor peptide
      and a control peptide. Treatment with the inhibitor was found to significantly
      decrease the heart weight/body weight ratio, the size of cardiac myocytes, and
      the serum brain natriuretic peptide and atrial natriuretic peptide levels. These
      results suggest that nuclear factor of activated T cells functions in a key role
      in the development of cardiac hypertrophy during pressure overload. Inhibition of
      nuclear factor of activated T cells by a specific inhibitor peptide is a suitable
      method for characterization of the molecular mechanisms underlying cardiac
      hypertrophy as well as in the search for new promising therapies for disease.

PMID- 16611218
TI  - Valproic acid promotes neurite outgrowth in PC12 cells independent from
      regulation of the survival of motoneuron protein.
AB  - Spinal muscular atrophy (SMA) is a neurodegenerative disorder of motoneurons. The
      disease is caused by deletions or mutations of the survival of motoneuron gene 1
      (SMN1). The amount of protein expressed from the second gene, SMN2, correlated
      with the severity of the clinical phenotype. The histone deacetylase inhibitor
      valproic acid (VPA) has been shown to increase the total cellular amount of
      functional SMN protein and is therefore considered as a drug candidate for
      treatment of SMA. In this study, we analyzed the effects of VPA in PC12 cells, a
      model system for neuronal differentiation, with regard to neurite outgrowth and
      SMN expression. VPA promoted neurite outgrowth in PC12 cells. However, this
      effect did not correlate with upregulation of SMN protein levels, suggesting a
      SMN-independent mechanism for VPA regulation of neurite outgrowth.

PMID- 16611219
TI  - Synthetic diether-linked cationic lipids for gene delivery.
AB  - Quaternary ammonium lipids 2a-p, with diether linkages between hydrocarbon chains
      and their ammonium headgroups, were synthesized as potential vectors for cationic
      liposome-mediated gene delivery. Varying the length of carbon chains and
      quaternary ammonium heads as well as different anionic complexes will enable the
      study of the structure-function relationships of these cationic lipids in terms
      of gene delivery properties.

PMID- 16611220
TI  - GPR55 as a new cannabinoid receptor: still a long way to prove it.

PMID- 16611222
TI  - Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy
      as a host defence mechanism.
AB  - A marquee feature of the powerful human pathogen Mycobacterium tuberculosis is
      its macrophage parasitism. The intracellular survival of this microorganism rests
      upon its ability to arrest phagolysosome biogenesis, avoid direct cidal
      mechanisms in macrophages, and block efficient antigen processing and
      presentation. Mycobacteria prevent Rab conversion on their phagosomes and
      elaborate glycolipid and protein trafficking toxins that interfere with Rab
      effectors and regulation of specific organellar biogenesis in mammalian cells.
      One of the major Rab effectors affected in this process is the type III
      phosphatidylinositol 3-kinase hVPS34 and its enzymatic product
      phosphatidylinositol 3-phosphate (PI3P), a regulatory lipid earmarking organellar
      membranes for specific trafficking events. PI3P is also critical for the process
      of autophagy, recently recognized as an effector of innate and adaptive immunity.
      Induction of autophagy by physiological, pharmacological or immunological
      signals, including the major antituberculosis Th1 cytokine IFN-gamma and its
      downstream effector p47 GTPase LRG-47, can overcome mycobacterial phagosome
      maturation block and inhibit intracellular M. tuberculosis survival. This review
      summarizes the findings centred around the PI3P-nexus where the mycobacterial
      phagosome maturation block and execution stages of autophagy intersect.

PMID- 16611223
TI  - Manipulating cellular transport and immune responses: dynamic interactions
      between intracellular Salmonella enterica and its host cells.
AB  - Intracellular survival and replication within eukaryotic host cells is of central
      importance for the pathogenesis of infections caused by Salmonella enterica.
      Intracellular Salmonella translocates a set of effector proteins by means of a
      type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2
      (SPI2) that manipulates normal host-cell functions. Intracellular survival and
      replication is linked to the function of the SPI2-T3SS, but recent observations
      show that many additional cellular functions are targeted by this virulence
      system. In this review, we focus on the recent observations on the interference
      of intracellular Salmonella with functions of the innate and adaptive immune
      system and the modification of endocytic and exocytic cellular transport. The
      common molecular basis of the different SPI2-dependent phenotypes could be the
      interference with cellular transport along microtubules.

PMID- 16611224
TI  - Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas
      gingivalis infected human aortic endothelial cells.
AB  - Epidemiological studies support that chronic periodontal infections are
      associated with an increased risk of cardiovascular disease. Previously, we
      reported that the periodontal pathogen Porphyromonas gingivalis accelerated
      atherosclerotic plaque formation in hyperlipidemic apoE-/- mice, while an
      isogenic fimbria-deficient (FimA-) mutant did not. In this study, we utilized 41
      kDa (major) and 67 kDa (minor) fimbria mutants to demonstrate that major fimbria
      are required for efficient P. gingivalis invasion of human aortic endothelial
      cells (HAEC). Enzyme-linked immunosorbent assay (ELISA) revealed that only
      invasive P. gingivalis strains induced HAEC production of pro-inflammatory
      molecules interleukin (IL)-1beta, IL-8, monocyte chemoattractant protein (MCP)-1,
      intracellular adhesion molecule (ICAM)-1, vascular cellular adhesion molecule
      (VCAM)-1 and E-selectin. The purified native forms of major and minor fimbria
      induced chemokine and adhesion molecule expression similar to invasive P.
      gingivalis, but failed to elicit IL-1beta production. In addition, the major and
      minor fimbria-mediated production of MCP-1 and IL-8 was inhibited in a dose
      dependent manner by P. gingivalis lipopolysaccharide (LPS). Both P. gingivalis
      LPS and heat-killed organisms failed to stimulate HAEC. Treatment of endothelial
      cells with cytochalasin D abolished the observed pro-inflammatory MCP-1 and IL-8
      response to invasive P. gingivalis and both purified fimbria, but did not affect
      P. gingivalis induction of IL-1beta. These results suggest that major and minor
      fimbria elicit chemokine production in HAEC through actin cytoskeletal
      rearrangements; however, induction of IL-1beta appears to occur via a separate
      mechanism. Collectively, these data support that invasive P. gingivalis and
      fimbria stimulate endothelial cell activation, a necessary initial event in the
      development of atherogenesis.

PMID- 16611225
TI  - CD11b is required for the resolution of inflammation induced by Bordetella
      bronchiseptica respiratory infection.
AB  - CD11b is a cell surface receptor that contributes to many cellular processes
      which are involved in the generation of a protective immune response against
      pathogenic organisms. In this work, the natural host-pathogen model of murine
      Bordetella bronchiseptica infection was used to explore the role of CD11b in
      respiratory immunity. Following intranasal inoculation, CD11b-/- mice rapidly
      succumb to B. bronchiseptica respiratory infection, highlighting the prominent
      role of CD11b in the generation of a protective immune response in this model.
      CD11b appears to be required for both the control of bacterial numbers and the
      regulation of cellular responses in the lungs. An increased accumulation of
      neutrophils in the lungs of CD11b-/- mice as compared with wild-type mice
      suggests that CD11b contributes to the regulation of cellular responses to
      respiratory infection. This accumulation may be explained by a decrease in
      apoptosis that is observed in the absence of CD11b following cellular
      interactions with B. bronchiseptica. Interestingly, this role for CD11b in the
      regulation of cellular accumulation appears to be critically important for the
      resolution of damage associated with the type III secretion system (TTSS) of B.
      bronchiseptica. These data provide new insight into the key role CD11b plays in
      the resolution of damage in the lower respiratory tract, as well as the B.
      bronchiseptica virulence determinant that induces it.

PMID- 16611226
TI  - Cortactin is essential for F-actin assembly in enteropathogenic Escherichia coli
      (EPEC)- and enterohaemorrhagic E. coli (EHEC)-induced pedestals and the alpha
      helical region is involved in the localization of cortactin to bacterial
      attachment sites.
AB  - Enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC)
      are important human pathogens. Upon attachment to host cells, EPEC and EHEC are
      able to induce actin polymerization, which accumulates, forming a pedestal-like
      structure beneath the attached bacteria. Using siRNA, we show here that EPEC- and
      EHEC-induced pedestals are dependent on cortactin, an F-actin-binding protein
      found in the mammalian cell cortex. Knock-down of cortactin by siRNA resulted in
      a dramatic reduction of the pedestal formation induced by both pathogens. We also
      show that disruption of the Src homology 3 (SH3) domain of cortactin, or its
      downregulation by specific point mutations, negatively affects pedestal
      formation, suggesting that this domain is important for regulation of F-actin
      assembly by EPEC and EHEC. Green fluorescent protein (GFP) fused with the SH3
      domain (GFP-SH3), proline-rich region (GFP-PRR) or alpha-helical region of
      cortactin markedly reduced the amount of F-actin at the bacterial attachment
      sites. Interestingly, neither GFP-SH3 nor GFP-PRR was recruited to the vicinity
      of the bacterial adherence sites; however, GFP fused to the alpha-helical region
      was efficiently recruited and colocalized with the attached bacteria. These
      results demonstrate that cortactin is a requirement for pedestal formation and
      suggest a novel function for the predicted alpha-helical region of cortactin in
      actin assembly induced by EPEC and EHEC.

PMID- 16611227
TI  - Membrane perforations inhibit lysosome fusion by altering pH and calcium in
      Listeria monocytogenes vacuoles.
AB  - Listeria monocytogenes (Lm) evade microbicidal defences inside macrophages by
      secreting a pore-forming cytolysin listeriolysin O (LLO), which allows Lm to
      escape vacuoles. LLO also inhibits Lm vacuole fusion with lysosomes, which
      indicates LLO alters vacuole chemistry prior to release of Lm into cytoplasm.
      Using fluorescent probes to measure membrane permeability, calcium and pH, we
      identified small membrane perforations in vacuoles containing wild-type but not
      LLO-deficient (hly-) Lm. The small membrane perforations released small
      fluorescent molecules and persisted for several minutes before expanding to allow
      exchange of larger fluorescent molecules. Macropinosomes and hly- Lm vacuoles
      acidified and increased their calcium content ([Ca2+]vac) within minutes of
      formation; however, the small perforations made by LLO-expressing bacteria
      increased vacuolar pH and decreased [Ca2+]vac shortly after infection.
      Experimental increases in vacuolar pH inhibited Lm vacuole fusion with lysosomes.
      The timing of perforation indicated that LLO-dependent delays of Lm vacuole
      maturation result from disruption of ion gradients across vacuolar membranes.

PMID- 16611228
TI  - Attachment and fusion of endoplasmic reticulum with vacuoles containing
      Legionella pneumophila.
AB  - Legionella pneumophila is an intracellular pathogen that replicates in a unique
      vacuole that avoids endocytic maturation. Previous studies have shown host
      vesicles attached to the L. pneumophila-containing vacuole (LCV) minutes after
      uptake. Here we examine the origin and content of these vesicles by electron
      microscopy (EM). Our data demonstrate that the attached vesicles are derived from
      endoplasmic reticulum (ER) based the presence of the resident ER proteins glucose
      6-phosphatase, protein disulphide isomerase (PDI) and proteins having the ER
      retention signal lysine-aspartic acid-glutamic acid-leucine (KDEL). After
      tethering occurred, ER markers inside of attached vesicles were delivered into
      the lumen of the LCV, indicating ER fusion. Treatment of cells with brefeldin A
      did not interfere with the attachment of ER vesicles with the LCV, suggesting
      that tethering of these vesicles does not require activities mediated by ADP
      ribosylation factor (ARF). ER vesicles were not tethered to the LCV in cells
      producing the Sar1H79G protein, indicating that vesicles produced by the
      Sar1/CopII system are necessary for vesicle attachment. From these data we
      conclude that formation of the organelle that supports L. pneumophila replication
      is a two-stage process that involves remodelling of the LCV by early secretory
      vesicles produced by the Sar1/CopII system, followed by attachment and fusion of
      ER.

PMID- 16611229
TI  - The ability to form biofilm influences Mycobacterium avium invasion and
      translocation of bronchial epithelial cells.
AB  - Organisms of the Mycobacterium avium complex (MAC) are widely distributed in the
      environment, form biofilms in water pipes and potable water tanks, and cause
      chronic lung infections in patients with chronic obstructive pulmonary disease
      and cystic fibrosis. Pathological studies in patients with pulmonary MAC
      infection revealed granulomatous inflammation around bronchi and bronchioles.
      BEAS-2B human bronchial epithelial cell line was used to study MAC invasion. MAC
      strain A5 entered polarized BEAS-2B cells with an efficiency of 0.1 +/- 0.03% in
      2 h and 11.3 +/- 4.0% in 24 h. In contrast, biofilm-deficient transposon mutants
      5G4, 6H9 and 9B5 showed impaired invasion. Bacteria exposed to BEAS-2B cells for
      24 h had greater ability to invade BEAS-2B cells compared with bacteria incubated
      in broth. M. avium had no impact on the monolayer transmembrane resistance.
      Scanning electron microscopy showed that MAC A5 forms aggregates on the surface
      of BEAS-2B cell monolayers, and transmission electron microscopy evidenced MAC
      within vacuoles in BEAS-2B cells. Cells infected with the 5G4 mutant, however,
      showed significantly fewer bacteria and no aggregates on the cell surface.
      Mutants had impaired ability to cause infection in mice, as well. The ability to
      form biofilm appeared to be associated with the invasiveness of MAC A5.

PMID- 16611230
TI  - Exoenzyme S of Pseudomonas aeruginosa is not able to induce apoptosis when cells
      express activated proteins, such as Ras or protein kinase B/Akt.
AB  - Intracellular targeting of the Pseudomonas aeruginosa toxins, such as exoenzyme S
      (ExoS), cause cell death, as well as morphological and physiological changes in
      various tissue culture cells and animal models. In this report we have
      investigated the mechanism behind ExoS-mediated cell death. In order to address
      this issue, we have used cell lines expressing activated forms of various
      components of the Ras signalling pathway in order to evaluate the importance of
      the Ras pathway for viability and survival upon ExoS infection. Here we show that
      activated Ras is able to protect cells against cell death, regardless of whether
      it has been ADP-ribosylated by ExoS. Further, an activated form of protein kinase
      B (PKB)/Akt also leads to decreased level of cell death in response to ExoS
      infection, indicating that an important ExoS survival target is located upstream
      of Raf-1 and PKB/Akt. Moreover, we show that ExoS infection inhibits
      phosphorylation of FOXO3a, and induces caspase-3 activity, which are hallmarks
      for induction of cell death. In conclusion, we suggest that Ras proteins are an
      important cellular target for the P. aeruginosa toxin ExoS, which induces cell
      death during pathogenesis as a means of defending the bacterium against
      eukaryotic phagocytosis.

PMID- 16611232
TI  - A Salmonella type III secretion effector interacts with the mammalian
      serine/threonine protein kinase PKN1.
AB  - Essential to salmonellae pathogenesis is an export device called the type III
      secretion system (TTSS), which mediates the transfer of bacterial effector
      proteins from the bacterial cell into the host cell cytoplasm. Once inside the
      host cell, these effectors are then capable of altering a variety of host
      cellular functions in order to promote bacterial survival and colonization. SspH1
      is a Salmonella enterica serovar Typhimurium TTSS effector that localizes to the
      mammalian nucleus and down-modulates production of proinflammatory cytokines by
      inhibiting nuclear factor (NF)-kappaB-dependent gene expression. To identify
      mammalian binding partners of SspH1 a yeast two-hybrid screen against a human
      spleen cDNA library was performed. It yielded a serine/threonine protein kinase
      called protein kinase N 1 (PKN1). The leucine-rich repeat domain of SspH1 was
      demonstrated to mediate this interaction and also inhibition of NF-kappaB
      dependent gene expression. This suggested that PKN1 may play a role in modulation
      of the NF-kappaB signalling pathway. Indeed, we found that expression of
      constitutively active PKN1 in mammalian cells results in a decrease, while
      depletion of PKN1 by RNA interference causes an increase in NF-kappaB-dependent
      reporter gene expression. These data indicate that SspH1 may inhibit the host's
      inflammatory response by interacting with PKN1.

PMID- 16611231
TI  - Cholesterol-rich membrane microdomains mediate cell cycle arrest induced by
      Actinobacillus actinomycetemcomitans cytolethal-distending toxin.
AB  - We have previously shown that Actinobacillus actinomycetemcomitans cytolethal
      distending toxin (Cdt) is a potent immunosuppressive agent that induces G2/M
      arrest in human lymphocytes. In this study, we explored the possibility that Cdt
      mediated immunotoxicity involves lipid membrane microdomains. We first determined
      that following treatment of Jurkat cells with Cdt holotoxin all three Cdt
      subunits localize to these microdomains. Laser confocal microscopy was employed
      to colocalize the subunits with GM1-enriched membrane regions which are
      characteristic of membrane rafts. Western blot analysis of isolated lipid rafts
      also demonstrated the presence of Cdt peptides. Cholesterol depletion, using
      methyl beta-cyclodextrin, protected cells from the ability of the Cdt holotoxin
      to induce G2 arrest. Moreover, cholesterol depletion reduced the ability of the
      toxin to associate with Jurkat cells. Thus, lipid raft integrity is vital to the
      action of Cdt on host cells. The implications of our observations with respect to
      Cdt mode of action are discussed.

PMID- 16611233
TI  - The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a
      role in pathogenesis.
AB  - The ability of an isogenic set of mutants of Salmonella enterica serovar
      Typhimurium L354 (SL1344) with defined deletions in genes encoding components of
      tripartite efflux pumps, including acrB, acrD, acrF and tolC, to colonize
      chickens was determined in competition with L354. In addition, the ability of
      L354 and each mutant to adhere to, and invade, human embryonic intestine cells
      and mouse monocyte macrophages was determined in vitro. The tolC and acrB
      knockout mutants were hyper-susceptible to a range of antibiotics, dyes and
      detergents; the tolC mutant was also more susceptible to acid pH and bile and
      grew more slowly than L354. Complementation of either gene ablated the phenotype.
      The tolC mutant poorly adhered to both cell types in vitro and was unable to
      invade macrophages. The acrB mutant adhered, but did not invade macrophages. In
      vivo, both the acrB mutant and the tolC mutant colonized poorly and did not
      persist in the avian gut, whereas the acrD and acrF mutant colonized and
      persisted as well as L354. These data indicate that the AcrAB-TolC system is
      important for the colonization of chickens by S. Typhimurium and that this system
      has a role in mediating adherence and uptake into target host cells.

PMID- 16611234
TI  - Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity: differential
      activities of tetra- and penta-acylated lipid A structures on E-selectin
      expression and TLR4 recognition.
AB  - Porphyromonas gingivalis is a gram-negative bacterium strongly associated with
      periodontitis, a chronic inflammatory disease of the tissue surrounding the tooth
      root surface. Lipopolysaccharide (LPS) obtained from P. gingivalis is unusual in
      that it has been shown to display an unusual amount of lipid A heterogeneity
      containing both tetra- and penta-acylated lipid A structures. In this report, it
      is shown that penta-acylated lipid A structures facilitate E-selectin expression
      whereas tetra-acylated lipid A structures do not. Furthermore, it is shown that
      tetra-acylated lipid A structures are potent antagonists for E-selectin
      expression. Both tetra- and penta-acylated lipid A structures interact with TLR4
      although experiments utilizing human, mouse and human/mouse chimeric TLR4
      proteins demonstrated that they interact differentially with the TLR4 signalling
      complexes. The presence of two different structural types of lipid A in P.
      gingivalis LPS, with opposing effects on the E-selectin response suggests that
      this organism is able to modulate innate host responses by alterations in the
      relative amount of these lipid A structures.

PMID- 16611235
TI  - Role of Shiga toxin versus H7 flagellin in enterohaemorrhagic Escherichia coli
      signalling of human colon epithelium in vivo.
AB  - Enterohaemorrhagic Escherichia coli O157:H7 (EHEC) is a clinically important
      foodborne pathogen that colonizes human colon epithelium and induces acute
      colonic inflammation, but does not invade the epithelial cells. Whereas Shiga
      toxin (Stx) and bacterial flagellin have been studied for their ability to
      upregulate the production of proinflammatory chemokines by cultured human colon
      cancer cell lines, the relevance of studies in colon cancer cell lines to the
      production of proinflammatory signals by normal epithelial cells in EHEC-infected
      human colon is not known. We show herein that Stx does not bind to human colon
      epithelium in vivo. Moreover, globotriaosylceramide (Gb3/CD77) synthase, the
      enzyme required for synthesis of the Gb3/CD77 receptor for Stx, was not expressed
      by normal or inflamed human colon epithelium in vivo. In contrast, Toll-like
      receptor (TLR) 5, the receptor for bacterial flagellin, was expressed by normal
      human colon epithelium and by colon epithelium in human intestinal xenografts.
      EHEC H7 flagellin instilled in the lumen of human colon xenografts that contain
      an intact human epithelium upregulated the expression of epithelial cell
      proinflammatory chemokines, which was accompanied by a subepithelial influx of
      neutrophils. Isogenic mutants of EHEC that lacked flagellin did not significantly
      upregulate prototypic neutrophil and dendritic cell chemoattractants by model
      human colon epithelia, irrespective of Stx production. We conclude that EHEC H7
      flagellin and not Stx is the major EHEC factor that directly upregulates
      proinflammatory chemokine production by human colon epithelium in vivo.

PMID- 16611236
TI  - RNAi is an antiviral immune response against a dsRNA virus in Drosophila
      melanogaster.
AB  - Drosophila melanogaster has a robust and efficient innate immune system, which
      reacts to infections ranging from bacteria to fungi and, as discovered recently,
      viruses as well. The known Drosophila immune responses rely on humoral and
      cellular activities, similar to those found in the innate immune system of other
      animals. Recently, RNAi or 'RNA silencing' has arisen as a possible means by
      which Drosophila can react to a specific pathogens, transposons and retroviral
      elements, in a fashion similar to that of a traditional mammalian adaptive immune
      system instead of in a more generalized and genome encoded innate immune-based
      response. RNAi is a highly conserved regulation and defence mechanism, which
      suppresses gene expression via targeted RNA degradation directed by either
      exogenous dsRNA (cleaved into siRNAs) or endogenous miRNAs. In plants, RNAi has
      been found to act as an antiviral immune response system. Here we show that RNAi
      is an antiviral response used by Drosophila to combat infection by Drosophila X
      Virus, a birnavirus, as well. Additionally, we identify multiple core RNAi
      pathway genes, including piwi, vasa intronic gene (vig), aubergine (aub),
      armitage (armi), Rm62, r2d2 and Argonaute2 (AGO2) as having vital roles in this
      response in whole organisms. Our findings establish Drosophila as an ideal model
      for the study of antiviral RNAi responses in animals.

PMID- 16611237
TI  - Modulation of Alp4 function in Schizosaccharomyces pombe induces novel phenotypes
      that imply distinct functions for nuclear and cytoplasmic gamma-tubulin
      complexes.
AB  - The gamma-tubulin complex acts as a nucleation unit for microtubule assembly. It
      remains unknown, however, how spatial and temporal regulation of the complex
      activity affects microtubule-mediated cellular processes. Alp4 is one of the
      essential components of the S. pombe gamma-tubulin complex. We show here that
      overproduction of a carboxy-terminal form of Alp4 (Alp4C) and its derivatives
      tagged to a nuclear localization signal or to a nuclear export signal affect
      localization of gamma-tubulin complexes and induces novel phenotypes that reflect
      distinct functions of nuclear and cytoplasmic gamma-tubulin complexes. Nuclear
      Alp4C induces a Wee1-dependent G2 delay, reduces the levels of the gamma-tubulin
      complex at the spindle pole body, and results in defects in mitotic progression
      including spindle assembly, cytoplasmic microtubule disassembly, and chromosome
      segregation. In contrast, cytoplasmic Alp4C induces oscillatory nuclear movement
      and affects levels of cell polarity markers, Bud6 and Tip1, at the cell ends.
      These results demonstrate that regulation of nuclear gamma-tubulin complex
      activity is essential for cell cycle progression through the G2/M boundary and M
      phase, whereas regulation of cytoplasmic gamma-tubulin complex activity is
      important for nuclear positioning and cell polarity control during interphase.

PMID- 16611238
TI  - The carboxy-terminus of Alp4 alters microtubule dynamics to induce oscillatory
      nuclear movement led by the spindle pole body in Schizosaccharomyces pombe.
AB  - Alp4 is an essential component of the S. pombe gamma-tubulin complex.
      Overproduction of the carboxy-terminus of Alp4 induces oscillatory nuclear
      movement led by the spindle pole body (SPB). The movement is not dependent on
      cytoplasmic dynein dhc1, or kinesin-related proteins pkl1 and klp2. Rates of SPB
      movement correlate with elongation rates of microtubules (MTs) extending
      backwards from the moving SPB (backward-extending MTs), showing that pushing
      forces exerted by backward-extending MTs move the nucleus via the SPB. These
      backward-extending MTs are more stable than those of control cells and, thus, are
      able to push the SPB further towards the cell end, inducing nuclear oscillation
      with larger amplitudes than in control cells. SPB movement is biased towards the
      new end of the cell where levels of the CLIP170 homolog Tip1 increase, suggesting
      that the movement is related to MT-mediated cell polarity control. These results
      demonstrate that the carboxy-terminus of Alp4 alters MT dynamics and induces
      nuclear oscillation by modulating a nuclear positioning mechanism based on the
      balance of MT pushing forces, and suggest that regulation of gamma-tubulin
      complex activity is important for controlling MT dynamics and nuclear
      positioning.

PMID- 16611239
TI  - Oocyte growth-dependent progression of maternal imprinting in mice.
AB  - In mammals, some genes categorized as imprinted genes are exclusively expressed
      either from maternal or paternal allele. This parental-origin-specific gene
      expression is regulated by epigenetic modification of DNA methylation in
      differentially methylated region (DMR), which is independently imposed during
      oogenesis and spermatogenesis. It is known that methylation of DMR in the female
      germ line is established during oocyte growth phase. However, the cause of the
      progression of methylation on DMR, due to either aging of mice or growth-size of
      oocyte was unclear up to now. Here, we analyzed the methylation of DMR for each
      eight imprinted genes (Igf2r, Lit1, Zac1, Snrpn, Peg1/Mest, Impact, Meg1/Grb10,
      and H19) by bisulfite sequencing methylation assay, using oocytes from 10 dpp
      (days post partum), 15 dpp, 20 dpp, and adult mice. To find whether the size of
      oocytes is the cause of methylation, above oocytes were classified into seven
      groups (each oocyte diameter ranging from 40 to 75 microm with intervals of 5
      microm). The results from juvenile mice oocytes showed that DMR methylation
      progressed according to oocyte growth each imprinted gene. More than 85% of DMR
      methylation was achieved for both Igf2r, Zac1 & Lit1 with oocyte size of reaching
      55 microm and Snrpn, Peg1/Mest, Impact, and Meg1/Grb10 with oocyte size of
      reaching 60 microm. Preferential methylation of maternal allele was observed in
      Zac1 and Peg1/Mest of juvenile oocytes and in Snrpn of juvenile and adult
      oocytes. The oocyte size-dependent-methylation progressed equally for all three
      different-age juvenile mice. The size-dependent-methylation was also recognized
      in the growing oocytes collected from adult mice, although the progress is
      slightly slower than that of juvenile mice. From these results, we concluded that
      DNA methylation is established with oocyte size dependent manner, not with aging
      of mice.

PMID- 16611240
TI  - Enhanced gene targeting efficiency by siRNA that silences the expression of the
      Bloom syndrome gene in human cells.
AB  - Gene targeting via homologous recombination is a powerful tool for studying gene
      function, but the targeting efficiency in human cell lines is too low for
      generating knockout mutants. Several cell lines null for the gene responsible for
      Bloom syndrome, BLM, have shown elevated targeting efficiencies. Therefore, we
      reasoned that gene targeting would be enhanced by transient suppression of BLM
      expression by RNA interference. To test this, we constructed a gene correction
      assay system to measure gene targeting frequencies using a disrupted hypoxanthine
      phosphoribosyltransferase (HPRT) locus in the human HT1080 cell line, and
      examined the effect of small interfering RNA (siRNA) for BLM on gene targeting.
      When HPRT-null cells pretreated with BLM siRNA were co-transfected with the siRNA
      and a gene correction vector, the gene targeting frequency was elevated three
      fold, while the random integration frequency was marginally affected. Remarkably,
      in BLM heterozygous (+/-) cells derived from HPRT-null cells, the BLM siRNA
      treatment gave more than five-fold higher targeting frequencies, even with one
      tenth the amount of BLM siRNA used for BLM+/+ cells. Furthermore, in the human
      pre-B cell line Nalm-6, the siRNA treatment enhanced gene targeting 6.3-fold and
      > 5.8-fold at the HPRT and adenine phosphoribosyltransferase (APRT) loci,
      respectively. These results indicate that transient suppression of BLM expression
      by siRNA stimulates gene targeting in human cells, facilitating a further
      improvement of gene targeting protocols for human cell lines.

PMID- 16611241
TI  - TFII-I down-regulates a subset of estrogen-responsive genes through its
      interaction with an initiator element and estrogen receptor alpha.
AB  - TFII-I was initially identified as the general transcription factor that binds to
      initiator (Inr) elements in vitro. Subsequent studies have shown that TFII-I
      activates transcription of various genes either through Inr elements or through
      other upstream elements in vivo. Since, however, most studies so far on TFII-I
      have been limited to over-expression and reporter gene assays, we reevaluated the
      role of TFII-I in vivo by using stable knockdown with siRNA and by examining the
      expression of endogenous genes. Contrary to the widely accepted view, here we
      show that TFII-I is not important for cell viability in general but rather
      inhibits the growth of MCF-7 human breast cancer cells. MCF-7 cells are known to
      proliferate in an estrogen-dependent manner. Through analysis of TFII-I's cell
      type specific growth inhibitory effect, we show evidence that TFII-I down
      regulates a subset of estrogen-responsive genes, only those containing Inr
      elements, by recruiting estrogen receptor (ER) alpha and corepressors to these
      promoters. Thus, this study has revealed an unexpected new role of TFII-I as a
      negative regulator of transcription and cell proliferation.

PMID- 16611242
TI  - OMA-1 is a P granules-associated protein that is required for germline
      specification in Caenorhabditis elegans embryos.
AB  - In Caenorhabditis elegans, CCCH-type zinc-finger proteins have been shown to be
      involved in the differentiation of germ cells during embryonic development.
      Previously, we and others have identified novel redundant CCCH-type zinc-finger
      proteins, OMA-1 and OMA-2, that are involved in oocyte maturation. In this study,
      we report that the cytoplasmic expression level of OMA-1 protein was largely
      reduced after fertilization. In contrast to its cytoplasmic degradation, OMA-1
      was found to accumulate exclusively on P granules in germline blastomeres during
      embryogenesis. A notable finding is that embryos with partially suppressed oma-1;
      oma-2 expression showed inappropriate germline specification, including abnormal
      distributions of PGL-1, MEX-1 and PIE-1 proteins. Thus, our results suggest that
      oma gene products are novel multifunctional proteins that participate in crucial
      processes for germline specification during embryonic development.

PMID- 16611243
TI  - The MAPKKK Mekk1 regulates the expression of Turandot stress genes in response to
      septic injury in Drosophila.
AB  - Septic injury triggers a rapid and widespread response in Drosophila adults that
      involves the up-regulation of many genes required to combat infection and for
      wound healing. Genome-wide expression profiling has already demonstrated that
      this response is controlled by signaling through the Toll, Imd, JAK-STAT and JNK
      pathways. Using oligonucleotide microarrays, we now demonstrate that the MAPKKK
      Mekk1 regulates a small subset of genes induced by septic injury including
      Turandot (Tot) stress genes. Our analysis indicates that Tot genes show a complex
      regulation pattern including signals from both the JAK-STAT and Imd pathways and
      Mekk1. Interestingly, Mekk1 flies are resistant to microbial infection but
      susceptible to paraquat, an inducer of oxidative stress. These results point to a
      role of Mekk1 in the protection against tissue damage and/or protein degradation
      and indicate complex interactions between stress and immune pathways in
      Drosophila.

PMID- 16611244
TI  - Bacterial nucleoid dynamics: oxidative stress response in Staphylococcus aureus.
AB  - A single-molecule-imaging technique, atomic force microscopy (AFM) was applied to
      the analyses of the genome architecture of Staphylococcus aureus. The
      staphylococcal cells on a cover glass were subjected to a mild lysis procedure
      that had maintained the fundamental structural units in Escherichia coli. The
      nucleoids were found to consist of fibrous structures with diameters of 80 and 40
      nm. This feature was shared with the E. coli nucleoid. However, whereas the E.
      coli nucleoid dynamically changed its structure to a highly compacted one towards
      the stationary phase, the S. aureus nucleoid never underwent such a tight
      compaction under a normal growth condition. Bioinformatic analysis suggested that
      this was attributable to the lack of IHF that regulate the expression of a
      nucleoid protein, Dps, required for nucleoid compaction in E. coli. On the other
      hand, under oxidative conditions, MrgA (a staphylococcal Dps homolog) was over
      expressed and a drastic compaction of the nucleoid was detected. A knock-out
      mutant of the gene encoding the transcription factor (perR) constitutively
      expressed mrgA, and its nucleoid was compacted without the oxidative stresses.
      The regulatory mechanisms of Dps/MrgA expression and their biological
      significance were postulated in relation to the nucleoid compaction.

PMID- 16611245
TI  - The DnaA homolog of the hyperthermophilic eubacterium Thermotoga maritima forms
      an open complex with a minimal 149-bp origin region in an ATP-dependent manner.
AB  - In Escherichia coli, ATP-DnaA, but not ADP-DnaA, forms an initiation complex that
      undergoes site-specific duplex DNA unwinding, open complex formation. However, it
      remains unclear how highly the ATP-dependent activation of the initiation factor
      is conserved in evolution. The hyperthermophile Thermotoga maritima is one of the
      most ancient eubacteria in evolution. Here, we show that the DnaA homolog
      (tmaDnaA) of this bacterium forms open complexes with the predicted origin region
      (tma-oriC) in vitro. TmaDnaA has a strong and specific affinity for ATP/ADP as
      well as for 12-mer repeating sequences within the tma-oriC. Unlike ADP-tmaDnaA,
      ATP-tmaDnaA is highly cooperative in DNA binding and forms open complexes in a
      manner that depends on temperature and the superhelical tension of the tma-oriC
      bearing plasmid. The minimal tma-oriC required for unwinding is a 149-bp region
      containing five repeats of the 12-mer sequence and two AT-rich 9-mer repeats.
      TmaDnaA-binding to the 12-mer motif provokes DNA bending. The 9-mer region is the
      duplex-unwinding site. The tmaDnaA-binding and unwinding motifs of tma-oriC share
      sequence homology with corresponding archaeal and eukaryotic sequences. These
      findings suggest that the ATP-dependent molecular switch of the initiator and the
      mechanisms in the replication initiation complex are highly conserved in
      eubacterial evolution.

PMID- 16611246
TI  - Structural insight of human DEAD-box protein rck/p54 into its substrate
      recognition with conformational changes.
AB  - Human rck/p54, a product of the gene cloned at the breakpoint of t(11; 14)
      (q23;q32) chromosomal translocation on 11q23 in B-cell lymphoma, is a member of
      the DEAD-box RNA helicase family. Here, the crystal structure of Nc-rck/p54, the
      N-terminal core domain of rck/p54, revealed that the P-loop in motif I formed a
      closed conformation, which was induced by Asn131, a residue unique to the RCK
      subfamily. It appears that ATP does not bind to the P-loop. The results of
      dynamic light scattering revealed to ATP-induced conformational change of
      rck/p54. It was demonstrated that free rck/p54 is a distended molecule in
      solution, and that the approach between N-terminal core and C-terminal domains
      for ATP binding would be essential when unwinding RNA. The results from helicase
      assay using electron micrograph, ATP hydrolytic and luciferase assay showed that
      c-myc IRES RNA, whose secondary structure regulates IRES-dependant translation,
      was unwound by rck/p54 and indicated that it is a good substrate for rck/p54.
      Over-expression of rck/p54 in HeLa cells caused growth inhibition and cell cycle
      arrest at G2/M with down-regulation of c-myc expression. These findings
      altogether suggest that rck/p54 may affect the IRES-dependent translation of c
      myc even in the cells.

PMID- 16611247
TI  - Human scribble, a novel tumor suppressor identified as a target of high-risk HPV
      E6 for ubiquitin-mediated degradation, interacts with adenomatous polyposis coli.
AB  - Recently, we have identified human scribble (hScrib), human homolog of the
      Drosophila tumor suppressor Scribble, as a substrate of human papillomavirus E6
      oncoproteins for ubiquitin-mediated degradation dependent on ubiquitin-protein
      ligase E6AP. Human Scribble, classified as a LAP protein containing leucine-rich
      repeats and PDZ domains, interacts with E6 through its PDZ domains and C-terminal
      PDZ domain-binding motif of E6 protein. Interaction between human Discs Large
      (hDlg), which is a substrate of E6 for the ubiquitin-mediated degradation, and
      adenomatous polyposis coli (APC) has been shown. Here, we investigated whether
      hScrib and APC interact with each other in vitro and in vivo. Interaction between
      hScrib and APC is mediated by the PDZ domains 1 and 4 of hScrib and C-terminal
      PDZ domain-binding motif of APC. Human Scribble co-localized with APC at the
      synaptic sites of hippocampal neuron and at the tip of membrane protrusion in the
      epithelial cell line. Interference of the interaction between hScrib and APC
      caused disruption of adherens junction. Knockdown of hScrib expression by RNAi
      disrupts localization of APC at the adherens junction. These data suggest that
      hScrib may participate in the hDlg-APC complex through its PDZ domains and
      regulate cell cycle and neural function by associating with APC.

PMID- 16611248
TI  - An accurate, high-throughput method for genotyping the -373AnTn polymorphism in
      the interleukin-6 promoter.

PMID- 16611249
TI  - Molecular diversity of HLA-A*19 group of alleles in south Indian population.
AB  - To determine the genetic diversity of the human leucocyte antigen (HLA)-A*19
      group of alleles in the south Indian Tamil population, we studied 100 random
      healthy unrelated individuals. The frequency of HLA-A*19 was 37% with A*33
      (45.9%), A*32 (29.7%), A*31 (16.2%), A*30 (5.4%), A*29 (2.7%) and A*74 (0%). The
      frequency distribution of the HLA-A*19 alleles was distinct and revealed marked
      similarities and variations with other populations.

PMID- 16611250
TI  - Polymorphism in the proximal promoter region of the perforin gene and its impact
      on the course of HIV infection.
AB  - Cytotoxic T lymphocytes (CTLs) play an essential role in the control of viral
      replication during human immunodeficiency virus (HIV) infection. However, the
      efficacy of the CTL response varies between individuals. We tested the hypothesis
      that genetic polymorphisms in the lytic effector molecule perforin could
      influence the progression of HIV infection. The perforin gene was screened for
      single nucleotide polymorphisms (SNPs) by denaturing high-performance liquid
      chromatography (dHPLC). Correlations were sought between perforin genotype,
      perforin expression and lytic function of CD8+ T lymphocytes from HIV-positive
      patients. Association of perforin genotype with disease progression was
      investigated in 426 seroconverters enrolled in the French SEROCO cohort. AIDS
      free survival curves were constructed using the Kaplan-Meier method and compared
      using the log-rank test. Three SNPs were found in the proximal promoter region of
      the perforin gene: 63G (allelic frequency 0.029), 112G (allelic frequency 0.071)
      and 1012T (allelic frequency 0.070). The presence of the 1012T genotype
      correlated with fewer perforin+ cells among circulating CD8+ CTL. However, CTL
      lines from HIV(-positive) individuals heterozygous for the perforin 1012T SNP
      displayed normal lysis of target cells, and within the SEROCO cohort, patients
      heterozygous for the 1012T SNP showed normal disease progression. However,
      1012T/T homozygotes showed a tendency towards slower disease progression (P =
      0.08). In conclusion, polymorphism in the perforin gene is limited, and although
      the 1012T genotype appears to influence perforin expression, it was not
      conclusively associated with disease progression in HIV infection.

PMID- 16611251
TI  - TNF-857 polymorphism in Israeli Jewish patients with inflammatory bowel disease.
AB  - Tumour necrosis factor (TNF)-alpha is an important pro-inflammatory cytokine that
      has been implicated in the pathogenesis of inflammatory bowel disease (IBD). The
      promoter TNF-857 C-->T single nucleotide polymorphism (SNP) is functional through
      the binding to the transcription factor octamer transcription factor-1 (OCT-1).
      In order to investigate the frequency of this SNP in Israeli Jewish IBD patients,
      we analysed a cohort of well-characterized patients, 153 with Crohn's disease
      (CD) and 78 with ulcerative colitis (UC) and 188 healthy controls individually
      matched for age, sex and ethnicity. Forty-one per cent of the patients were of
      Ashkenazi and 48% were of non-Ashkenazi background. The remaining 11% were of
      mixed Ashkenazi-non-Ashkenazi background. Patients and controls were genotyped
      for the TNF-857 SNP by Taqman technology. Stratification for the CARD15
      Arg702Trp, Gly908Arg and Leu1007fsinsC mutations took place in 136 CD patients.
      Carrier frequency of TNF-857T between CD and controls (36% vs. 40%; P = 0.556;
      OR: 1.18, 95% CI 0.74-1.88), or between UC and controls (41% vs. 37%; P = 0.743;
      OR: 0.85, 95% CI 0.45-1.62) did not differ significantly. Neither did stratifying
      for the presence of at least one of the common CARD15 mutations result in a
      significant difference between CD and controls. No associations were found
      between TNF-857T and CD phenotype as defined by the Vienna classification,
      perianal disease or extra-intestinal disease irrespective of CARD15 carrier
      status. In conclusion, it appears that TNF-857 SNP does not contribute to
      susceptibility of IBD, neither does it define the phenotype of CD in Israeli
      Jewish IBD patients.

PMID- 16611252
TI  - Thyroid autoantibody production is influenced by exon 1 and promoter CTLA-4
      polymorphisms in patients with Hashimoto's thyroiditis.
AB  - Strong genetic susceptibility to thyroid autoantibody (TAb) diathesis has been
      shown and one of the major genes involved is probably CTLA-4 gene. Our recent
      study of patients with Graves' disease has demonstrated that exon 1 CTLA-4 gene
      polymorphism influences higher TAb production. Here, we evaluated the influence
      of exon 1 and promoter CTLA-4 polymorphisms on TAb production in 109 newly
      diagnosed patients with Hashimoto's thyroiditis (HT). Serum TSH, thyroid
      peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) were measured.
      49 A/G and -318 C/T polymorphisms were detected using polymerase chain reaction
      amplification of genomic DNA and restriction fragment length polymorphism
      analysis. Patients with AG and GG genotype had significantly higher TPOAb median
      values compared to patients with AA genotype (P < 0.003). Similarly, TgAb median
      value was significantly higher in AG patients and in the entire G-allele carrying
      group (P < 0.02). Compared to both T-allele carrying genotypes, CC genotype
      presented with significantly higher TPOAb median value (P < 0.02), whereas TgAb
      median values did not differ significantly between various genotypes. In
      conclusion, our results indicate that G allele influences higher TPOAb and TgAb
      production, whereas C allele affects especially TPOAb production in patients with
      HT. Therefore, our findings provide further evidence that CTLA-4 is a major TAb
      susceptibility gene.

PMID- 16611253
TI  - HLA class II genetic diversity in southern Tunisia and the Mediterranean area.
AB  - North Africa is populated by many Arab- and Berber-speaking populations whose
      genetic history is still poorly understood. In this study, we analyse the HLA
      DRB1 and DQB1 molecular diversity in three populations from the south of Tunisia-
      Berbers from Jerba, Berbers from Matmata and Arabs from Gabes--and we compare
      them to a large set of populations from the whole Mediterranean region. Among the
      three populations studied, the Berbers from Jerba are the most peculiar, as they
      diverge significantly from other North Africans while being genetically highly
      diversified and close to populations from the Near East. Thus, Jerba may have
      been a crossing point, in historical times, where colonization from the eastern
      Mediterranean area left significant genetic traces. By contrast, the populations
      from Matmata and Gabes are genetically similar to other Arab and Berber-speaking
      populations from different areas of the Maghrib, despite some peculiar allele and
      haplotype frequencies. At a larger scale, northwest Africa and southwest Europe
      are closely related according to these polymorphisms, while the populations from
      the eastern Mediterranean area are much more differentiated. The close genetic
      relatedness found for HLA among populations of the western Mediterranean region
      challenges previous results based on Y chromosome analyses, where the Gibraltar
      Strait appeared to constitute a main genetic barrier.

PMID- 16611254
TI  - The synergistic effects of the IL-9 gene and environmental exposures on asthmatic
      Taiwanese families as determined by the transmission/disequilibrium test.
AB  - Asthma occurs in genetically susceptible individuals in the presence of
      environmental factors. The interleukin-9 (IL-9) gene, one of the cytokine genes
      located on chromosome 5q31, plays an important role in the development of
      asthmatic syndrome by enhancing both T-cell and mast-cell function. This study
      investigated GT repeat polymorphism of the IL-9 gene and the gene-environment
      interactions, which may predispose individuals to asthma and atopy pathogenesis.
      In this study, we used the transmission/disequilibrium test (TDT) to investigate
      the relationship between asthma and the IL-9 gene by studying 123 parent
      offspring trios and 91 siblings. For allele-specific TDT chi-squared test, allele
      122 of the IL-9 gene showed significant association with asthmatics with specific
      IgE against house dust (HD) (P = 0.038). The additions of covariates to TDT to
      conduct the synergistic effects between the IL-9 gene and environmental factors
      into account were estimated by conditional logistic regression models. The odds
      ratio for transmission of allele 122 of the IL-9 gene was 1.23 (P = 0.28) for all
      asthmatic probands. There was slight increased interaction effect on asthma
      between transmission of allele 122 of IL-9 gene to offspring and who were exposed
      to the fur of pets (OR = 3.33, P = 0.047). We also detected elevated odds of
      transmission of allele 122 to atopic asthmatic probands (OR = 2.08, P = 0.03) and
      offspring with very high levels of serum IgE (> or = 800 IU mL(-1)). In
      conclusion, this study has found that the IL-9 gene was slightly associated with
      asthmatics who have positive specific IgE against Der p (or Der f) and house
      dust, when information on environmental factors was incorporated as effect
      modifiers.

PMID- 16611255
TI  - Serum IgE levels in neurofibromatosis 1.
AB  - A descriptive case study was performed on 75 patients with NF1 (neurofibromatosis
      type 1) from the CNNF (Brazil) database. Serum IgE levels were determined using
      the IgE radioimmunosorbent test, with the reference values of 75-502 IU mL(-1).
      The patients were divided into groups, with 25 patients presenting plexiform
      neurofibromas, 25 presenting neurofibromas and 25 presenting no neurofibromas.
      The purposes of this study were to determine the serum IgE levels of patients
      with NF1 presenting plexiform neurofibromas, neurofibromas and no neurofibromas,
      as well as to determine possible correlations between serum IgE levels and the
      size of the plexiform neurofibromas and neurofibromas presented by these
      patients. Elevated serum IgE levels were observed in all the patient groups. We
      did not observe a correlation between IgE levels and age in these patients;
      however, we did observe correlations between IgE levels and neurofibroma and
      plexiform neurofibroma size. We suggest further studies to confirm these results
      and to investigate in greater depth the possible role of IgE in the development
      and growth of neurofibromas and plexiform neurofibromas in NF1.

PMID- 16611256
TI  - Genetic analysis of HLA, NA and HPA typing in type 2 diabetes and ASO.
AB  - We examined the genetic status of human leucocyte antigens (HLA), human platelet
      alloantigens (HPA) and neutrophil-specific antigens (NA) in patients with type 2
      diabetes mellitus and diabetic arteriosclerosis obliterans (ASO). To our
      knowledge, the present study is the first report showing the relationship among
      three genetic factors in type 2 diabetes mellitus and ASO patients. HLA typing
      was performed by the polymerase chain reaction (PCR)-restriction fragment length
      polymorphism method. HPA-typing and NA-typing were by a PCR-sequence-specific
      primer method. The incidence of HLA-DRB1*1501 was found to be significant in type
      2 diabetes and non-diabetic, particularly ASO-positive patients, compared to
      control subjects. There were no differences in NA1/NA2 between the control and
      diabetic or non-diabetic ASO groups. However, the frequency of NA2/NA2 in ASO
      positive diabetes and non-diabetic ASO patients was significantly higher than
      controls. The a/b genotype of HPA-5a/5b was significantly lower in type 2
      diabetes and non-diabetic ASO-positive patients than in controls. These findings
      suggest that genetic studies of HLA, NA and HPA could be useful to understand the
      pathogenesis of type 2 diabetes and ASO.

PMID- 16611257
TI  - A91V perforin variation in healthy subjects and FHLH patients.
AB  - Familial haemophagocytic lymphohistiocytosis (FHLH) is a heterogeneous autosomal
      recessive disorder characterized by hyperactivation of monocytes/macrophages.
      Perforin (PRF1) gene alterations have been documented in 40% of patients with
      FHLH. Although several mutations have been identified, a clear correlation
      between the individual molecular alteration and the phenotypic expression of the
      disease is still unclear. In particular, the role that the A91V substitution
      plays in the pathogenesis of the disease is still controversial. In the effort to
      make a conclusive remark to this issue, we here report on the frequency of the
      A91V mutation in a group of unrelated healthy families obtained from the "Centre
      d'Etude du Polymorphisme Humain" (CEPH), which are considered representative of
      the worldwide population. This frequency was compared to that observed in FHLH
      patients recruited through the Italian National Registry. The frequency in CEPH
      healthy subjects is 3.7%, thus indicating that the alteration represents a
      polymorphism. However, the frequency of this alteration in FHLH patients
      associated with PRF1 mutation is much higher than that observed in controls
      (26.2%, P = 0.0002), suggesting that the alteration is an important genetic
      susceptibility factor.

PMID- 16611258
TI  - Stromal cell-derived factor 1 (SDF1) genetic polymorphism in a sample of healthy
      individuals, seronegative individuals exposed to human immunodeficiency virus
      type 1 (HIV-1) and patients infected with HIV-1 from the Brazilian population.
AB  - The interaction of viral and host factors is believed to determine not only the
      risk for initial human immunodeficiency virus type 1 (HIV-1) acquisition but also
      the course of the infection. Genetic polymorphisms in the chemokine receptors and
      their ligands were related to the susceptibility and resistance to HIV-1
      infection. A polymorphism in the conserved 3' untranslated region of the stromal
      cell-derived factor-1 (SDF1) gene, which encodes a ligand of the CXCR4 receptor,
      has been related either to delayed progression to AIDS or to rapid disease
      progression and death. Global, regional, and ethnic distributions of frequencies
      of SDF1 genotypes and of the SDF1-3'A allele vary significantly. Although the HIV
      1 epidemic is increasing in Brazil, little information about the frequencies of
      host genetic mutations related to HIV/AIDS resistance in the Brazilian population
      has been reported. To address this question, this study was carried out in order
      to determine the frequencies of the SDF1 polymorphism and the SDF1-3'A allele on
      1061 genomic DNA samples purified from peripheral blood cells of 136 healthy
      individuals (group 1), 147 HIV-1-exposed seronegative individuals (group 2), 161
      HIV-1-infected asymptomatic individuals and with CD4(+) T-cells count 350 mm(-3)
      (group 3), and 617 HIV-1-infected individuals with AIDS and/or CD4(+) T-cells
      count < 350 mm(-3) (group 4). The frequencies of the SDF1-3'A homozygous mutation
      were 3.7%, 6.1%, 4.3%, and 5.3% among groups 1, 2, 3, and 4, respectively (P =
      0.5120). The overall frequency of the SDF1-3'A allele was 0. 1984 and did not
      differ among the four groups (P = 0.2744). The results underscore the global
      distribution of the SDF1 polymorphism and the hypothesis that the SDF1-3'A
      allele, itself, may not be sufficient to prevent the risk of HIV-1 infection and
      may be not related to the progression of the disease in the Brazilian population.

PMID- 16611259
TI  - HSP70-hom gene single nucleotide (+2763 G/A and +2437 C/T) polymorphisms in
      sarcoidosis.
AB  - In the present study, two coding polymorphisms within the heat shock protein 70
      hom gene (HSP70-hom) were analysed. One hundred and thirty-eight individuals were
      studied, including 42 Polish patients with sarcoidosis, 13 of which presented
      with Lofgren's syndrome (LS), and 94 control subjects. Dimorphisms at positions
      +2763 (A/G) and +2437 (C/T) of the HSP70-hom gene were typed using amplification
      refractory mutation system and polymerase chain reaction-restriction fragment
      length polymorphism technique, respectively. A significant prevalence of the
      HSP(+2437)-C allele and the HSP(+2437)-CC homozygous genotype was observed in
      patients with sarcoidosis and in those presenting with LS as compared to controls
      (P < 0.001 in all comparisons made). A majority of HLA-DRB1*03-positive patients
      with LS were carrying both HSP(+2437)-C and (+2763)-G alleles, and the
      concomitant presence of these three genetic factors was more frequent among
      patients with LS as compared to patients without LS (0.54 vs. 0.17, P < 0.05) and
      controls (0.54 vs. 0.01, P < 0.001). The association of the HSP(+2437)-C allele
      with sarcoidosis and LS appeared to be independent of the presence of DRB1*03,
      although this HLA specificity was associated with LS manifestation. The
      HSP(+2763)-G allele was independently associated with neither sarcoidosis nor LS.
      However, this HSP(+2763)-G allele was present with either DRB1*03 or HSP(+2437)-C
      within the same haplotypes in the patients and this might explain the observed
      prevalence of DRB1*03, HSP(+2437)-C and (+2763)-G in patients with LS. In
      conclusion, HSP(+2437)-C allele was found as a factor associating with
      susceptibility to sarcoidosis and LS.

PMID- 16611260
TI  - No evidence for association of the TP53 12139 and the BAX-248 polymorphisms with
      endemic pemphigus foliaceus (fogo selvagem).
AB  - Pemphigus foliaceus (PF) is an autoimmune bullous epidermal disease,
      characterized by autoantibodies specific to the desmosomal protein desmoglein 1
      (dsg1) and by acantholysis, the rupture of the cellular junctions among
      keratinocytes. Known also as fogo selvagem (wild fire) in Brazil, the disease has
      distinct epidemiological characteristics, being endemic in certain regions of
      South America. It is a multifactorial (complex) disease, with oligo- or polygenic
      disease susceptibility. In view of the previously reported evidences of a role
      for apoptosis dysregulation in pemphigus pathogenesis, we hypothesized that
      genetic variants of molecules participating in apoptosis may contribute to
      interindividual variation of susceptibility to PF. The TP53 12139(G,C) and the
      BAX-248(G,A) single nucleotide polymorphisms (SNP) were analysed in a genetic
      association study. The allelic, genotypic and allele carrier frequencies for
      these SNPs did not differ statistically between the patient and the control
      groups, for both the Euro- and the Afro-Brazilian population strata. The results
      of this study lead us to conclude that, although the TP53 and BAX alleles
      analysed differ functionally, this variation does not alter the functionality of
      the molecules in a way that would interfere with the development of the disease.

PMID- 16611261
TI  - Nomenclature for factors of the HLA system, update November 2005.

PMID- 16611262
TI  - Nomenclature for factors of the HLA system, update December 2005.

PMID- 16611263
TI  - Review article: hepatitis B and liver transplantation.
AB  - Liver transplantation is an excellent treatment for hepatitis B virus infected
      patients who have acute or chronic liver failure and/or primary liver cancer.
      Advances in antiviral prophylaxis prevent clinically significant graft re
      infection for the majority of patients. Graft and patient survival has improved
      significantly during the past decade, and results of transplantation for
      hepatitis B virus are now superior to those achieved for most other indications.
      In particular, the availability of lamivudine and adefovir have transformed
      outcome. The addition of lamivudine to passive immunoprophylaxis with hepatitis B
      virus immunoglobulin prevents re-infection in most cases. Adefovir should be
      added to this combination when the patient develops lamivudine resistance before
      transplantation. The significance of serum hepatitis B virus DNA positivity in
      the absence of circulating hepatitis B surface antigen is uncertain. Hepatitis B
      virus infection of the graft can be observed when prophylaxis is inadequate, when
      the donor liver contains latent hepatitis B virus infection (so-called de novo
      infection from the hepatitis B virus core antibody positive donor), and when the
      donor is exposed to third party infection (sexual or nosocomial transmission).
      Established hepatitis B virus graft infection is a good indication for
      combination nucleoside analogue therapy. Combination therapy can achieve
      sustained suppression of viral replication, and hepatitis B e antigen and
      hepatitis B surface antigen clearance can also be observed.

PMID- 16611264
TI  - Review article: predicting response in hepatitis C virus therapy.
AB  - The introduction of combination therapy with ribavirin and of pegylated
      interferons has improved treatment results in patients with chronic hepatitis C.
      However, overall rates of sustained virologic response following antiviral
      therapy of chronic hepatitis C still do not exceed 54-63%. Because of several
      virus- and patient-related factors, treatment is even less successful in some
      patient subpopulations. The major viral factors associated with impaired response
      are hepatitis C virus genotype 1 infection and a high viral load. Among patient
      related factors cirrhosis is of special importance. Baseline predictive factors
      for sustained virologic response become less important for prediction of
      treatment outcome when quantifications of hepatitis C virus RNA during early
      therapy are taken into account. This article provides a summary of virus- and
      patient-related parameters, which are prognostic for response to antiviral
      therapy in chronic hepatitis C and focuses on the prediction of treatment
      response by quantification of hepatitis C virus RNA concentration during therapy.

PMID- 16611265
TI  - Review article: thrombocytopenia in chronic liver disease and pharmacologic
      treatment options.
AB  - In patients with liver disease, thrombocytopenia is a clinical feature that may
      represent an obstacle to invasive diagnostic or therapeutic procedures,
      chemotherapy, and anti-viral treatment. Stimulation of the bone marrow is the
      most promising therapeutic intervention for thrombocytopenia in patients with
      chronic liver disease. The description of thrombopoietin and its (de)regulation
      in patients with chronic liver disease have disclosed new treatment
      opportunities. Indeed, pharmacologic treatment options for thrombocytopenia can
      be divided into treatments targeted at the thrombopoietin receptor (synthetic
      thrombopoietins and thrombopoietin-mimetic agents), and use of cytokines with
      general thrombopoietic potential. Unfortunately, use of synthetic thrombopoietin
      was hampered by the development of neutralizing antibodies, and thrombopoietin
      mimetic agents have not yet entered clinical studies. Interleukin-11 proved to be
      useful in increasing platelet count in patients with chronic liver disease,
      although its use is limited by side-effects. Erythropoietin has shown promising
      results in improving thrombocytopenia in cirrhotic patients. In patients with
      chronic liver disease, safe and well-tolerated treatments aimed at improving
      thrombocytopenia are still lacking. Larger studies are needed to evaluate and
      better characterize the thrombopoietic potential of erythropoietin. Human studies
      with thrombopoietin-mimetic agents are eagerly awaited in order to assess both
      effectiveness and safety of these drugs.

PMID- 16611266
TI  - Review article: intestinal serotonin signalling in irritable bowel syndrome.
AB  - Alterations in motility, secretion and visceral sensation are hallmarks of
      irritable bowel syndrome. As all of these aspects of gastrointestinal function
      involve serotonin signalling between enterochromaffin cells and sensory nerve
      fibres in the mucosal layer of the gut, potential alterations in mucosal
      serotonin signalling have been explored as a possible mechanism of altered
      function and sensation in irritable bowel syndrome. Literature related to
      intestinal serotonin signalling in normal and pathophysiological conditions has
      been searched and summarized. Elements of serotonin signalling that are altered
      in irritable bowel syndrome include: enterochromaffin cell numbers, serotonin
      content, tryptophan hydroxylase message levels, 5-hydroxyindoleacedic acid
      levels, serum serotonin levels and expression of the serotonin-selective reuptake
      transporter. Both genetic and epigenetic factors could contribute to decreased
      serotonin-selective reuptake transporter in irritable bowel syndrome. A serotonin
      selective reuptake transporter gene promoter polymorphism may cause a genetic
      predisposition, and inflammatory mediators can induce serotonin-selective
      reuptake transporter downregulation. While a psychiatric co-morbidity exists with
      IBS, changes in mucosal serotonin handling support the concept that there is a
      gastrointestinal component to the aetiology of irritable bowel syndrome.
      Additional studies will be required to gain a more complete understanding of
      changes in serotonin signalling that are occurring, their cause and effect
      relationship, and which of these changes have pathophysiological consequences.

PMID- 16611267
TI  - Systematic review: are probiotics useful in controlling gastric colonization by
      Helicobacter pylori?
AB  - Helicobacter pylori is a highly prevalent pathogen considered as an aetiological
      factor for gastroduodenal ulcers, and a risk factor for gastric adenocarcinoma
      and lymphoma in humans. Most subjects colonized by this micro-organism are
      asymptomatic and remain untreated. In symptomatic patients, the antibiotic
      treatment has a high cost and is not 100% effective because of resistance to
      antibiotics and to moderate patient compliance. This review discusses the role of
      probiotics as alternative solutions to assist in the control of H. pylori
      colonization in at-risk populations. The evidence that some strains of
      Lactobacillus and Bifidobacterium are able to inhibit H. pylori growth through
      the release of bacteriocins or organic acids, and may also decrease its adhesion
      to epithelial cells, is reviewed. In addition, probiotics have a possible role in
      the stabilization of the gastric barrier function and the decrease of mucosal
      inflammation. Other aspects that are considered are the contribution of
      probiotics to the healing of the gastric mucosa linked to their antioxidant and
      anti-inflammatory properties. Clinical trials in colonized adults and children
      are reviewed, and suggest that probiotics do not eradicate H. pylori but maintain
      lower levels of this pathogen in the stomach; in combination with antibiotics,
      probiotics may increase eradication rate and/or decrease adverse effects. Papers
      suggesting similar effects on H. pylori by foodstuffs such as berry juice and
      some milk proteins are quoted. Regular intake of these and other dietary products
      might constitute a low-cost, large-scale alternative solution applicable for
      populations at-risk for H. pylori colonization.

PMID- 16611268
TI  - Systematic review: the management of pouchitis.
AB  - Pouchitis is the most common complication following proctocolectomy and ileal
      pouch-anal anastomosis in patients with ulcerative colitis. We aim at discussing
      relevant information on epidemiology, clinical features, risk factors, diagnostic
      testing, differential diagnosis and treatment of this idiopathic inflammatory
      condition. A computerized search of PubMed was performed with the search term
      'pouchitis', limited to English papers on humans. This strategy identified 514
      references. Relevant articles were selected from this list. In addition, the
      reference list for each of the selected articles was reviewed to identify any
      additional references. Pouchitis occurs in up to 60% of patients after ileal
      pouch-anal anastomosis for ulcerative colitis, and has characteristic clinical,
      endoscopic and histological features. The most important test for diagnosis is
      pouch endoscopy with biopsy. Antibiotics remain the mainstay of treatment, and
      other options are discussed for those patients who are refractory to antibiotic
      therapy.

PMID- 16611269
TI  - Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's
      disease.
AB  - BACKGROUND: Crohn's disease is associated with small bowel cancer whilst risk of
      colorectal cancer is less clear. AIM: To ascertain the combined estimates of
      relative risk of these cancers in Crohn's disease. METHODS: MEDLINE was searched
      to identify relevant papers. Exploding references identified additional
      publications. When two papers reviewed the same cohort, the later study was used.
      RESULTS: Meta-analysis showed overall colorectal cancer relative risk in Crohn's
      disease as 2.5 (1.3-4.7), 4.5 (1.3-14.9) for patients with colonic disease and
      1.1 (0.8-1.5) in ileal disease. Meta-regression showed reduction in relative risk
      over the past 30 years. Subgroup analysis showed Scandinavia had significantly
      lower colorectal cancer relative risk than the UK and North America. Cumulative
      risk analysis showed 10 years following diagnosis of Crohn's disease relative
      risk of colorectal cancer is 2.9% (1.5%-5.3%). Meta-analysis showed small bowel
      cancer relative risk in Crohn's disease is 33.2 (15.9-60.9). Small bowel cancer
      relative risk has not significantly reduced over the last 30 years. CONCLUSION:
      Relative risk of colorectal and small bowel cancers are significantly raised in
      Crohn's disease. Cumulative risk of colorectal cancer of 2.9% at 10 years
      suggests a potential benefit from routine screening. However, the value of
      screening requires rigorous appraisal.

PMID- 16611270
TI  - Meta-analysis: the dialysis mode and immunological response to hepatitis B virus
      vaccine in dialysis population.
AB  - BACKGROUND: Patients on maintenance dialysis typically show a suboptimal immune
      response to hepatitis B virus vaccine compared with the non-uraemic population.
      Some authors have claimed that dialysis mode has an impact on the immune response
      to hepatitis B virus vaccine but consistent information is lacking on this issue.
      AIM: To evaluate the relationship between dialysis mode and immune response to
      hepatitis B vaccine in dialysis population by performing a systematic review with
      a meta-analysis of clinical trials. METHOD: We used the random effects model of
      DerSimonian and Laird; sources of heterogeneity in effect estimates were explored
      by performing sensitivity analyses. RESULTS: The relative risk of failure to
      respond to hepatitis B vaccine among patients who underwent maintenance
      haemodialysis vs. peritoneal dialysis was the end point of interest. We
      identified 14 clinical trials involving 1211 unique patients on maintenance
      dialysis. Pooling of study results did not show a significant decreased risk of
      response to hepatitis B vaccine among haemodialysis patients (overall risk ratio:
      1.0, 95% confidence intervals: 0.92-1.1). The P-value was 0.13 for our test of
      study heterogeneity. CONCLUSION: There is no significant link between dialysis
      mode and seroresponse to hepatitis B virus vaccine in dialysis population.

PMID- 16611271
TI  - Personal view: a potential novel treatment for fatigue complicating chronic liver
      disease--how should its efficacy be evaluated?
AB  - Profound fatigue is a clinically significant complication of chronic liver
      disease. A mechanism of fatigue in experimental animals and male athletes appears
      to be increased serotoninergic neurotransmission in the brain. Recently, attempts
      have been made to assess the efficacy of a serotonin antagonist, specifically the
      5-HT3 receptor subtype antagonist, ondansetron, in ameliorating fatigue in
      patients with chronic liver disease. However, the results of a randomized
      controlled trial of ondansetron for fatigue in patients with primary biliary
      cirrhosis did not indicate that ondansetron was either effective or ineffective.
      The reasons for the uncertain outcome of the randomized controlled trial are not
      clear. One contributing factor may have been the use of subjective indices of
      fatigue as primary efficacy endpoints. There is a need to develop objective
      quantitative primary efficacy endpoints for use in trials of therapy for fatigue.
      Another contributing factor may relate to the conduct of a randomized controlled
      trial not invariably being the optimal approach to resolve a specific clinical
      issue, particularly when the application of statistical methods yields equivocal
      findings. When the results of a randomized controlled trial are indecisive,
      findings based on clinical judgement, medicine's most important asset, should be
      carefully evaluated.

PMID- 16611272
TI  - Antibiotic treatment of Crohn's disease: results of a multicentre, double blind,
      randomized, placebo-controlled trial with rifaximin.
AB  - BACKGROUND: Clinicians often employ antibiotics in Crohn's disease. Rifaximin is
      active against bacteria frequently found in the intestinal mucosa of Crohn's
      disease patients. AIM: To evaluate the difference in efficacy between once and
      twice/daily oral administration of rifaximin and placebo in the treatment of
      active Crohn's disease. METHODS: We enrolled 83 patients with mild-to-moderate
      Crohn's disease and randomized to three treatments for 12 weeks: Group A
      (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C
      (placebo b.d.). RESULTS: Clinical remission was achieved by 52% of Group B, 32%
      (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C),
      without reaching a statistically significant difference. Treatment failures were:
      4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of
      rifaximin 800 mg b.d. were significantly higher than those of placebo and
      rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P <
      0.05). CONCLUSIONS: Rifaximin 800 mg b.d. was superior to placebo in inducing
      clinical remission of active Crohn's disease. Although this difference was not
      statistically significant, the number of the failures in the placebo group was
      significantly higher than those who received rifaximin 800 mg b.d.

PMID- 16611273
TI  - Maintenance infliximab does not result in increased abscess development in
      fistulizing Crohn's disease: results from the ACCENT II study.
AB  - BACKGROUND: Rapid fistula healing may predispose Crohn's disease patients to
      abscess development. AIM: Data from ACCENT II were analysed to determine whether
      fistula-related abscess development is affected by infliximab exposure. METHODS:
      Following infliximab 5 mg/kg infusions at weeks 0, 2 and 6, patients were
      evaluated for fistula response for two consecutive visits at least 4 weeks apart.
      Patients (N = 282) were randomized at week 14 to either placebo or infliximab 5
      mg/kg every 8 weeks through week 46. If response was lost at or after week 22,
      patients could crossover to a 5 mg/kg higher infliximab dose. Fistula-related
      abscesses were diagnosed by physical examination or by imaging procedures
      according to usual practice. RESULTS: Infliximab exposure was approximately
      twofold higher for the infliximab maintenance group. Twenty-one (15%) patients in
      the infliximab maintenance group had at least one newly developed fistula-related
      abscess compared with 27 (19%) in the placebo maintenance group (P = 0.526). The
      proportion of patients with a new fistula-related abscess was similar regardless
      of whether or not patients crossed over to a 5 mg/kg higher infliximab dose. The
      number of fistula-related abscesses diagnosed over time did not differ between
      groups. CONCLUSION: Abscess development in patients with fistulizing Crohn's
      disease is not dependent on cumulative infliximab exposure.

PMID- 16611274
TI  - Pharmacogenetics of thiopurine therapy in paediatric IBD patients.
AB  - BACKGROUND: Azathioprine is widely used in the treatment of children with
      inflammatory bowel disease. The occurrence and type of adverse events to
      azathioprine may be related to thiopurine S-methyltransferase (TPMT) enzyme
      activity and to inosine triphophate pyrophosphatase (ITPase) deficiency. AIM:
      Investigate frequencies of functional TPMT polymorphisms and ITPA polymorphisms
      and their association with the occurrence of adverse events during azathioprine
      therapy in a paediatric inflammatory bowel disease population. METHODS: Seventy
      two azathioprine treated paediatric inflammatory bowel disease patients, 47%
      girls, mean age 12.5 years (range 6.5-17.5), were assessed for TPMT and ITPA
      polymorphisms and for adverse events. The relation between polymorphisms and
      adverse events is evaluated. RESULTS: Of all azathioprine treated patients, 11
      experienced an adverse event for which azathioprine was stopped: pancreatitis (n
      = 4), leucopenia (n = 2) and 'general malaise' (n = 5). Of the 11 patients who
      stopped azathioprine because of adverse events, 10 had wild-type alleles for all
      investigated genotypes. Genotyping of ITPA 94C>A polymorphisms showed that two
      patients were homozygous, both tolerated azathioprine well. CONCLUSIONS: No
      association of functional ITPA and TPMT polymorphisms and the occurrence of
      azathioprine related adverse events could be detected. Pharmacogenetic assessment
      prior to thiopurine therapy does not seem warranted.

PMID- 16611275
TI  - Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic
      steatosis in patients with non-alcoholic fatty liver disease: a pilot study.
AB  - BACKGROUND: Recent studies suggest a role of n-3 long-chain polyunsaturated fatty
      acids (n-3 PUFA) as peroxisome proliferator-activated receptor-alpha ligands in
      improving non-alcoholic fatty liver disease (NAFLD) in rodents. However, data in
      humans are still lacking. AIM: To evaluate the efficacy of prolonged PUFA
      supplementation in patients with NAFLD. METHODS: Fifty-six patients with NAFLD
      were enrolled. Among the overall eligible patients, 42 assumed n-3 PUFA 1-g
      capsule daily for 12 months, whereas 14 refused the treatment and were analysed
      as controls. All patients underwent haematochemical and ultrasound follow-up.
      RESULTS: Polyunsaturated fatty acid supplementation significantly decreased serum
      aspartate transaminase (P = 0.003), alanine transaminase (P = 0.002), gamma
      glutamyl transpeptidase (P = 0.03), triglycerides (P = 0.02) and fasting glucose
      (P = 0.02) in comparison with controls. Circulating arachidonate and n-6/n-3
      fatty acid ratio was reduced (P = 0.0002, and P = 0.0001 respectively) in treated
      patients. Moreover, ultrasonography demonstrated improvement of liver echotexture
      after PUFA (P = 0.0001), and increase of Doppler perfusion index (P = 0.001),
      whereas no significant changes occurred in controls. CONCLUSIONS: Supplementation
      with n-3 PUFA improves biochemical, ultrasonographic and haemodynamic features of
      liver steatosis. Our study supports the efficacy of n-3 PUFA as a new therapeutic
      approach in the treatment of NAFLD.

PMID- 16611276
TI  - Effect of anti-viral therapy for occult hepatitis C virus infection.
AB  - BACKGROUND: Occult hepatitis C virus infection is defined by the presence of
      hepatitis C virus-RNA in liver but with undetectable anti-hepatitis C virus and
      serum viral RNA. AIM: To study the response to anti-viral therapy in occult
      hepatitis C virus infection to assess the pathogenic effect of occult hepatitis C
      virus. METHODS: Ten patients with occult hepatitis C virus infection were treated
      with pegylated-interferon plus ribavirin for 24 weeks and were followed-up 24
      weeks after therapy. All patients had abnormal alanine aminotransferase,
      hepatitis C virus-RNA positive in peripheral blood mononuclear cells and liver
      necroinflammation. RESULTS: At the end of treatment and follow-up, the percentage
      of patients with normal alanine aminotransferase was 80% (95% CI: 48-96%) and 60%
      (95% CI: 31-84%) respectively, and hepatitis C virus-RNA in peripheral blood
      mononuclear cells was negative in 80% (95% CI: 48-96%) and 70% (95% CI: 40-90%)
      cases. At the end of follow-up sustained response was observed in 30% (95% CI: 11
      61%) of cases. Five patients underwent a second liver biopsy. In all cases, liver
      hepatitis C virus-RNA persisted, although hepatitis C virus-RNA load was
      significantly lower (3.2 x 10(4) +/- 5.1 x 10(4) copies/microg RNA) than in the
      basal biopsy (2.4 x 10(5) +/- 3.8 x 10(5) copies/microg RNA); (P = 0.043).
      Necroinflammation and fibrosis decreased in three cases. CONCLUSION: The
      biochemical, virological and histological response to therapy achieved in
      patients with occult hepatitis C virus infection demonstrates the pathologic
      effects of occult hepatitis C virus.

PMID- 16611277
TI  - Assessing patients' understanding of hepatitis C virus infection and its impact
      on their lifestyle.
AB  - AIMS: To assess how much patients with hepatitis C virus infection know about
      their condition and what impact it has on their lifestyle. MATERIALS AND METHODS:
      A multiple-choice questionnaire was administered anonymously to 364 hepatitis C
      virus-infected subjects just before their first specialist visit. RESULTS: Even
      before hepatitis C virus infection was diagnosed, 257 subjects (70.6%) already
      knew something about this infection. Overall, 36% of patients had changed the way
      they behaved within the family, 25.5% had changed their sexual habits, 46.9% had
      changed their diet, and 69% reported having stopped or limited their alcohol
      intake after being told they were hepatitis C virus positive. Hepatitis C virus
      infection had a negative impact on the psychological status in 44.2% of patients.
      This effect was significantly greater among women and was independent of either
      the duration of their infection or any counselling received from the general
      practitioner. The need for specific treatment was reported by 59.8%. A demand for
      more detailed information about hepatitis C virus was expressed by 89.9% of
      patients. CONCLUSIONS: Hepatitis C virus changes all aspects of lifestyle and
      psychological status. The patients' strong demand for more information suggests
      that counselling and educational programmes must be an integral part of the
      activities of both the general practitioner and the specialist.

PMID- 16611278
TI  - 48 weeks pegylated interferon alpha-2a is superior to 24 weeks of pegylated
      interferon alpha-2b in achieving hepatitis B e antigen seroconversion in chronic
      hepatitis B infection.
AB  - BACKGROUND/AIM: Although 48-week therapy with pegylated-interferons has been
      shown to be effective for the treatment of chronic hepatitis B virus infection,
      the efficacy of a shorter duration of therapy with pegylated interferons is
      unknown. METHOD: We reviewed 53 hepatitis B e antigen positive Chinese patients
      treated with 48 weeks of pegylated interferon alpha-2a or 24 weeks of pegylated
      interferon alpha-2b. Sustained virological response was defined as hepatitis B e
      antigen seroconversion and hepatitis B virus DNA <10(5) copies/mL at week 72.
      RESULTS: Twenty-nine patients were treated with 48 weeks of pegylated-interferon
      alpha-2a and 24 patients with 24 weeks of pegylated-interferon-alpha-2b. At the
      end-of-therapy, hepatitis B e antigen seroconversion and hepatitis B virus DNA
      <10(5) copies/mL were similar between the two groups of patients [9/29 (31.0%)
      vs. 2/24 (8.3%), respectively, P = 0.09]. At week 72, 10 of the 29 patients
      (34.5%) treated with 48 weeks of pegylated-interferon-alpha-2a compared with two
      of the 24 patients (8.3%) treated with 24 weeks of pegylated-interferon-alpha-2b
      had sustained virological response (P = 0.04). By logistic analysis, 48 weeks of
      pegylated-interferon-alpha-2a was independently associated with sustained
      virological response (P = 0.04 adjusted hazards-ratio 9.37). CONCLUSION: Further
      studies are required to determine the optimal duration of therapy with pegylated
      interferons in chronic hepatitis B.

PMID- 16611280
TI  - Intragastric acid control in non-steroidal anti-inflammatory drug users:
      comparison of esomeprazole, lansoprazole and pantoprazole.
AB  - BACKGROUND: Studies to date have not directly compared the pharmacodynamic
      efficacies of different proton pump inhibitors in controlling intragastric
      acidity in patients treated with non-steroidal anti-inflammatory drugs. AIM: To
      compare acid suppression with once-daily esomeprazole 40 mg, lansoprazole 30 mg
      and pantoprazole 40 mg in patients receiving non-selective or cyclo-oxygenase-2
      selective non-steroidal anti-inflammatory drug therapy. METHODS: In this
      multicentre, open-label, comparative, three-way crossover study, adult patients
      (n = 90) receiving non-steroidal anti-inflammatory drugs were randomized to one
      of six treatment sequences. At the study site, patients were administered
      esomeprazole 40 mg, lansoprazole 30 mg and pantoprazole 40 mg for 5 days each,
      with a washout period of > or =10 days between each treatment. Twenty-four-hour
      pH testing was performed on day 5 of each dosing period. RESULTS: The mean
      percentage of time during the 24-h pH monitoring period that gastric pH was >4.0
      was significantly greater with esomeprazole (74.2%) compared with lansoprazole
      (66.5%; P < 0.001) and pantoprazole (60.8%; P < 0.001), and significantly greater
      with esomeprazole (P < 0.05) than with the comparators regardless of whether
      using non-selective vs. cyclo-oxygenase-2-selective non-steroidal anti
      inflammatory drugs. CONCLUSIONS: At the doses studied, esomeprazole treatment
      provides significantly greater gastric acid suppression than lansoprazole or
      pantoprazole in patients receiving non-selective or cyclo-oxygenase-2-selective
      non-steroidal anti-inflammatory drugs.

PMID- 16611279
TI  - Comparison of the effects of fasting morning, fasting evening and fed bedtime
      administration of tenatoprazole on intragastric pH in healthy volunteers: a
      randomized three-way crossover study.
AB  - BACKGROUND: The effectiveness of proton pump inhibitors is influenced by meals
      and administration time. AIM: To compare the effects on intragastric acidity of
      times of dosing of tenatoprazole, a novel imidazopyridine-based proton pump
      inhibitor with a prolonged plasma half-life. METHODS: This randomized three
      period crossover study included 12 Helicobacter pylori-negative healthy subjects,
      who received tenatoprazole 40 mg either fasting at 7.00 AM, fasting at 7.00 PM or
      fed at 9.30 PM for 7 days, with a 2-week washout between periods. Twenty-four
      hour intragastric pH was monitored on day 7 of each period. RESULTS: On day 7,
      median 24-h pH was 4.7, 5.1 and 4.7 after breakfast, dinner and bedtime dosing,
      respectively (P = 0.11), whereas night-time pH was 4.2, 5.0 and 4.4 (P = 0.13).
      The mean 24-h percentage of time over pH 4 was 62, 72 and 64 after breakfast,
      dinner and bedtime dosing, respectively (N.S.), and 54, 68 and 56 during night
      time (P = 0.06). Nocturnal acid breakthrough incidence decreased from 100% at
      baseline to 83%, 55% and 75% after 7.00 AM, 7.00 PM and 9.30 PM dosing,
      respectively (P = 0.18), and its mean duration dropped from 6.2 to 2.8, 1.0 and
      2.2 h, respectively (P < 0.05). CONCLUSION: Seven-day administration of
      tenatoprazole provides a prolonged duration of acid suppression, especially
      during the night-time, with little effect of food or time of dosing.

PMID- 16611281
TI  - Oesophagitis is common in patients with achalasia after pneumatic dilatation.
AB  - BACKGROUND: Achalasia, an oesophageal motor disease, is associated with
      functional oesophageal obstruction. Food stasis can predispose for oesophagitis.
      Treatment aims at lowering of the lower oesophageal sphincter pressure, enhancing
      the risk of gastro-oesophageal reflux. Nevertheless, the incidence of
      oesophagitis after achalasia treatment is unknown. AIM: To investigate the
      incidence and severity of oesophagitis in achalasia patients treated with
      pneumatic dilatation. METHODS: A cohort of 331 patients with achalasia were
      treated with pneumatic dilatation and followed. Oesophagitis and stasis were
      assessed by endoscopy and inflammation was graded by histology. RESULTS: 251
      patients were followed for a mean values of 8.4 years (range: 1-26). The average
      number of endoscopies with biopsy sample sets per patient was 4 (range: 1-17).
      Three patients had no histological signs of oesophagitis throughout follow-up,
      139 had oesophagitis grade 1, 49 oesophagitis grade 2 and 60 grade 3. Specialized
      intestinal metaplasia was found in 37 patients. The association between
      endoscopic food stasis and histological inflammation was significant. The
      association between endoscopic signs of oesophagitis and histological
      inflammation was poor. CONCLUSIONS: Forty percent of the achalasia patients
      develop chronic active or ulcerating oesophagitis after treatment. Inflammation
      was associated with food stasis. Because the sensitivity of endoscopy to detect
      inflammation is low, surveillance endoscopy with biopsy sampling and assessment
      of stasis is warranted to detect early neoplastic changes.

PMID- 16611282
TI  - Pancreatic cancer in England and Wales 1975-2000: patterns and trends in
      incidence, survival and mortality.
AB  - BACKGROUND: Rates and time trends in mortality from pancreatic cancer vary
      considerably between countries. AIM: To examine trends and patterns in the
      incidence of, and the survival and mortality from, pancreatic cancer in England
      and Wales from 1975 to 2000; in particular, whether incidence and survival rates
      are related to socio-economic deprivation. METHODS: We calculated annual age
      specific and overall age-standardized incidence and mortality rates by sex for
      pancreatic cancer in total, and by subsite. We also estimated survival by sex and
      age group and by subsite. RESULTS: In males, the age-standardized rate fluctuated
      in the late 1970s, to peak at 13.0 per 100,000 in 1979, declined steadily by an
      average of 1.3% per year to around 10.3 per 100,000 in the mid-1990s and then
      levelled off. For females, the rate peaked at 8.4 per 100,000 in the late 1980s
      before declining and fluctuating around 7.7 per 100,000 in the late 1990s.
      Patterns and trends in mortality rates were closely similar to those in
      incidence, due to the very low survival rates: only 2-3% at 5 years from
      diagnosis. Survival rates improved only minimally over the period 1971-99.
      Incidence and mortality rates were slightly higher in both males and females
      living in the most deprived areas, but survival was not consistently related to
      socio-economic deprivation. CONCLUSIONS: The incidence of, and mortality from,
      pancreatic cancer in England and Wales have fallen from peak levels observed in
      the 1970s and 1980s, and levelled off in the 1990s for both sexes; survival rates
      remain very low.

PMID- 16611283
TI  - Reinfection after successful eradication of Helicobacter pylori: a 2-year
      prospective study in Alaska Natives.
AB  - BACKGROUND: Limited information exists regarding risk factors for reinfection
      after cure of Helicobacter pylori infection. AIM: To determine the 2-year
      reinfection rate of H. pylori in a cohort of urban Alaska Natives. METHODS:
      Participants over 18 years of age undergoing oesophagogastroduodenoscopy had
      (13)C urea breath test, culture, CLOtest and histology performed. Those diagnosed
      with H. pylori who tested urea breath test-negative at 8 weeks after treatment
      were followed prospectively at 4 months, 6 months, 1 year and 2 years. Subjects
      experiencing H. pylori reinfection as defined by a positive urea breath test were
      compared with those who did not become reinfected using univariable and
      multivariable analysis. Risk of reinfection over time was estimated by the Kaplan
      Meier method. RESULTS: Helicobacter pylori reinfection occurred in 14 of 98
      subjects successfully treated. The cumulative reinfection rate was 5.1% (95% CI:
      0.7%-9.5%) at 4 months, 7.2% (2.0-12.3%) at 6 months, 10.3% (4.2-16.3%) at 1-year
      and 14.5% (7.5-21.6%) at 2 years. In multivariable analysis, a history of
      previous peptic ulcer disease or presence of ulcer at time of study
      oesophagogastroduodenoscopy were the only risk factors associated with
      reinfection (P = 0.01). CONCLUSIONS: Based on the findings from our study,
      subjects with a history of or current peptic ulcer disease should be followed,
      after successful treatment for H. pylori, with periodic urea breath test to
      detect reinfection, as reinfection would put them at high risk for ulcer
      recurrence.

PMID- 16611284
TI  - Effects of low-dose aspirin on gastric erosions, cyclooxygenase expression and
      mucosal prostaglandin-E2 do not depend on Helicobacter pylori infection.
AB  - BACKGROUND: The mechanisms by which Helicobacter pylori and low-dose aspirin
      induce gastric damage are not completely elucidated. AIM: To evaluate the effects
      of low-dose aspirin on gastric damage, mucosal prostaglandin-E(2) levels and
      cyclooxygenase-enzyme expression in relation to the H. pylori status. METHODS:
      Twenty healthy volunteers (H. pylori positive, n = 10; H. pylori negative, n =
      10) received aspirin 100 mg/die for 1 week. At days 0, 1, 3 and 7, gastric
      mucosal lesions were studied by oesophagogastroduodenoscopy and histology. COX-1
      and COX-2 were determined by immunohistochemistry and reverse-transcriptase
      polymerase chain reaction, and mucosal prostaglandin-E(2) levels by enzyme-linked
      immunosorbent assay. Nine H. pylori-positive subjects repeated the protocol after
      H. pylori eradication. RESULTS: All groups developed a similar number of
      erosions. COX-1 and COX-2 expression, as well as mucosal prostaglandin-E(2)
      levels were not influenced by H. pylori status and aspirin medication.
      Helicobacter pylori-negative and H. pylori-eradicated subjects who developed
      aspirin-induced erosions had significant lower pre-treatment antral prostaglandin
      E(2) levels than those without erosions (3.6 ng/microg vs. 6.3 ng/microg protein
      and 3.6 ng/microg vs. 6.0 ng/microg protein, respectively, P < 0.01 Mann-Whitney
      U-test). CONCLUSIONS: In healthy subjects, low-dose aspirin for 1 week does
      neither affect cyclooxygenase expression nor mucosal prostaglandin-E(2) levels.
      Antral prostaglandin-E(2)-basal levels appear to be critical for development of
      aspirin-induced gastric damage in subjects without H. pylori infection.

PMID- 16611285
TI  - Bovine lactoferrin for Helicobacter pylori eradication: an open, randomized,
      multicentre study.
AB  - BACKGROUND: Cure rates for eradication of Helicobacter pylori appear to be
      decreasing, thus more effective therapies must be identified. AIM: To evaluate
      the efficacy of bovine lactoferrin in the treatment of H. pylori infection.
      METHODS: In a multicentered prospective study, 402 (mean age 52.4, range 19-84
      years) H. pylori-positive patients were assigned to one of three regimens: group
      A - esomeprazole 20 mg b.d., clarithromycin 500 mg b.d. and tinidazole 500 mg
      b.d. for 7 days; group B - lactoferrin 200 mg b.d. for 7 days followed by the
      same schedule of group A; group C - esomeprazole 20 mg b.d., clarithromycin 500
      mg b.d. and tinidazole 500 mg b.d. plus lactoferrin 200 mg b.d. for 7 days.
      RESULTS: Of the 402 patients, 389 completed the study. Six patients were
      discontinued due to side effects, one patient in group B died and six patients
      were lost to follow up. The eradication rate (intention-to-treat analysis) was
      77% in group A (105/136), 73% in group B (97/132) and 90% in group C (120/134)
      (chi(2)-test P < 0.01). The incidence of side effects was 9.5% in group A, 9% in
      group B and 8.2% in group C (chi(2)-test P = 0.1). CONCLUSION: This study
      demonstrates that bovine lactoferrin is an effective adjuvant to 7-day triple
      therapy for eradication of H. pylori infection.

PMID- 16611287
TI  - Effect of intravenous infusion of glyceryl trinitrate on gastric and small
      intestinal motor function in healthy humans.
AB  - BACKGROUND: Glyceryl trinitrate is a donor of nitric oxide that relaxes smooth
      muscle cells of the gastrointestinal tract. Little is known about the effect of
      glyceryl trinitrate on gastric emptying and no data exist on the possible effect
      of glyceryl trinitrate on small intestinal transit. AIM: To examine the effect of
      intravenous infusion of glyceryl trinitrate on gastric and small intestinal motor
      function after a meal in healthy humans. METHODS: Nine healthy volunteers
      participated in a placebo-controlled, double-blind, crossover study. Each
      volunteer was examined during intravenous infusion of glyceryl trinitrate 1
      microg/kg x min or saline. A gamma camera technique was used to measure gastric
      emptying and small intestinal transit after a 1600-kJ mixed liquid and solid
      meal. Furthermore, duodenal motility was assessed by manometry. RESULTS: Glyceryl
      trinitrate did not change gastric mean emptying time, gastric half emptying time,
      gastric retention at 15 min or small intestinal mean transit time. Glyceryl
      trinitrate did not influence the frequency of duodenal contractions, the
      amplitude of duodenal contractions or the duodenal motility index. CONCLUSIONS:
      Intravenous infusion of glyceryl trinitrate 1 microg/kg x min does not induce
      major changes in gastric or small intestinal motor function after a 1600-kJ meal
      in healthy volunteers.

PMID- 16611288
TI  - Polyethylene glycol 4000 vs. lactulose for the treatment of neurogenic
      constipation in myelomeningocele children: a randomized-controlled clinical
      trial.
AB  - AIM: To compare the therapeutic effectiveness and tolerability of low daily doses
      of polyethylene glycol 4000 vs. lactulose in the treatment of neurogenic
      constipation in children with myelomeningocele. METHODS: Sixty-seven children
      with chronic neurogenic constipation were randomized allocated to receive either
      polyethylene glycol 4000 (0.50 g/kg) or lactulose (1.5 g/kg) for 6 months.
      Patients or their parents reported frequency and modality of evacuation and side
      effects on a diary card. Primary outcome was bowel frequency > or =3/week, and
      the second one was side effects at the end of treatment. RESULTS: Complete
      remission of constipation was reported by a significantly (P < 0.01) higher
      number of patients treated with polyethylene glycol compared with lactulose. At
      the end of the study, 46% patients of polyethylene glycol group and 22% of the
      lactulose group were asymptomatic. Compared with lactulose, patients treated with
      polyethylene glycol reported higher bowel frequency (5.1 vs. 2.9 bowel
      movements/week, P < 0.01) and reduction of encopresis. Neither lactulose nor
      polyethylene glycol caused clinically-significant serious side effects and
      palatability was similar. CONCLUSIONS: Polyethylene glycol 4000 compared with
      lactulose provided a higher success rate, without significant side effects, for
      the treatment of constipation in myelomeningocele children.

PMID- 16611286
TI  - Prokinetic effect of gut-oriented hypnosis on gastric emptying.
AB  - BACKGROUND: No data are available on the effect of hypnosis on gastric emptying.
      AIM: To determine the effect of a hypnosis session on gastric emptying and
      dyspeptic symptoms. METHODS: We studied emptying by ultrasonography and
      epigastric sensations in 11 healthy subjects and in 15 patients affected by
      functional dyspepsia under three conditions according to a fixed schedule: (a)
      basal, (b) after cisapride and (c) during a 90 min hypnotic trance. Eight healthy
      subjects repeated an emptying study listening to relaxing music. Statistical
      analysis was performed using the Friedman test or RM-ANOVA. RESULTS: In
      dyspeptics, the postprandial increase in the antral area was significantly
      smaller during the hypnosis trance than under the basal and the cisapride
      conditions. For the patients gastric emptying was significantly shortened by
      cisapride, and even more by hypnosis (basal 274 +/- 16.8 min; cisapride 227 +/-
      13.2; hypnosis 150 +/- 9.7) whereas for healthy subjects it was shortened only by
      hypnosis. The repeated study in healthy subjects listening to relaxing music
      showed no significant difference compared with the basal. Epigastric sensations
      were improved in dyspeptics by hypnosis, but not by cisapride. CONCLUSIONS: Gut
      oriented hypnosis is effective in shortening gastric emptying both in dyspeptic
      and in healthy subjects.

PMID- 16611289
TI  - The usefulness of transabdominal ultrasound for the diagnosis of lower
      gastrointestinal bleeding.
AB  - BACKGROUND: Lower gastrointestinal bleeding is a frequent cause of
      hospitalization, but diagnostic methods for this condition are not fully
      established. Transabdominal ultrasound is a widely accepted diagnostic tool in
      bowel diseases. AIM: To evaluate the usefulness of transabdominal ultrasound for
      lower gastrointestinal bleeding. METHODS: We reviewed the medical records of
      consecutive patients who underwent transabdominal ultrasound as the first
      diagnostic procedure for acute haematochezia during the period June 1999 to June
      2004. The study group comprised 111 patients and all underwent colonoscopy
      thereafter. Detection and diagnosis of lower gastrointestinal bleeding by
      ultrasonographic examination were evaluated by comparing the ultrasound diagnosis
      with the colonoscopic findings and final diagnosis. RESULTS: The bleeding site
      was localized by colonoscopy in 90 of the 111 patients (81%). The bleeding site
      was localized by ultrasound in 59 of the 90 patients (66%). When the bleeding
      site was in the rectum, ultrasonographic detectability was 30% (10/33);
      ultrasonographic detectability was 82-100% when the bleeding site was elsewhere.
      Rectal bleeding and diverticular bleeding were difficult to diagnose by
      ultrasound, but for the other diseases, diagnosis by ultrasonographic examination
      was possible in 91-100% of cases. CONCLUSIONS: Ultrasonographic examination may
      be an effective screening method for lower gastrointestinal bleeding.

PMID- 16611290
TI  - Treatment of anaemia in inflammatory bowel disease.

PMID- 16611292
TI  - Antibiotic prophylaxis for percutaneous endoscopic gastrostomy insertion in
      patients with non-malignant disease.

PMID- 16611294
TI  - Impracticalities of thiopurine S-methyltransferase determination in daily
      inflammatory bowel disease practice.

PMID- 16611296
TI  - Proton pump inhibitor failure in gastro-oesophageal reflux disease--what about
      eosinophilic oesophagitis?

PMID- 16611298
TI  - Levofloxacin-based rescue regimens after Helicobacter pylori treatment failure:
      how strong is the evidence?

PMID- 16611300
TI  - A century of Auer's rods.

PMID- 16611301
TI  - An unusual case of indigestion: persistence of phagocytosed Auer rods in acute
      promyelocytic leukaemia.

PMID- 16611302
TI  - Hereditary pyrimidine 5'-nucleotidase deficiency: from genetics to clinical
      manifestations.
AB  - Hereditary pyrimidine 5'-nucleotidase (P5'N) deficiency is the most frequent
      abnormality of the red cell nucleotide metabolism causing hereditary non
      spherocytic haemolytic anaemia. The disorder is usually characterised by mild-to
      moderate haemolytic anaemia associated with the accumulation of high
      concentrations of pyrimidine nucleotides within the erythrocyte. The precise
      mechanisms leading to the destruction of P5'N deficient red cells are still
      unclear. The pyrimidine 5'-nucleotidase type-I (P5'N-1) gene is localised on 7p15
      p14 and the cDNA has been cloned and sequenced; 20 mutations have been identified
      so far in 30 unrelated families, most of them at the homozygous level. Recently,
      the comparison of recombinant mutants of human P5'N-1 with the wild-type enzyme
      has enabled the effects of amino acid replacements on the enzyme molecular
      properties to be determined and help to correlate genotype to clinical phenotype.

PMID- 16611303
TI  - Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical
      phenotype.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is a variable clinical condition
      manifest by lymphoproliferative disease, autoimmune cytopenias and susceptibility
      to malignancy. Central to the cellular pathogenesis is defective FAS-induced
      apoptosis, which in turn leads to dysregulation of lymphocyte homeostasis. The
      majority of patients have heterozygous mutations in the FAS (TNFRSF6) gene, but
      the condition is genetically heterogeneous and mutations in FAS ligand and
      caspase-8 and caspase-10, all of which are involved in Fas mediated signalling,
      have also been identified. This review provides a detailed insight into the
      pathophysiology of lymphocyte apoptosis and how this relates to the variable and
      complex clinical manifestations of ALPS.

PMID- 16611304
TI  - A CD33-specific single-chain immunotoxin mediates potent apoptosis of cultured
      human myeloid leukaemia cells.
AB  - A novel single-chain immunotoxin was constructed by combining a CD33-specific
      single chain Fv (scFv) antibody fragment with an engineered variant of
      Pseudomonas exotoxin A (ETA). The variant toxin carries the KDEL peptide at its C
      terminus, a cellular peptide mediating improved retrograde transport to the
      endoplasmic reticulum. The purified recombinant fusion protein induced potent
      apoptosis of the human myeloid cell lines U937, HL-60 and THP-1. Up to 98% of
      U937 cells were eliminated after treatment for 72 h with a single dose of 500
      ng/ml (c. 7 nmol/l). Killing was antigen-specific and occurred by apoptosis. A
      control protein, consisting of a CD19-specific scFv antibody fragment fused to
      the ETA-KDEL toxin, failed to induce death of the CD19-negative cell lines U937,
      HL-60 and THP-1. The CD33-ETA toxin also mediated apoptosis of fresh patient
      derived acute myeloid leukaemia cells from bone marrow and peripheral blood. The
      pronounced antigen-restricted cytotoxicity of the novel fusion protein makes it a
      candidate for further evaluation of its therapeutic potential.

PMID- 16611305
TI  - Phase I/II study of vaccination with dendritic-like leukaemia cells for the
      immunotherapy of acute myeloid leukaemia.
AB  - Twenty-two patients with acute myeloid leukaemia were recruited into a phase I/II
      clinical trial investigating the vaccination of patients in complete remission
      (CR) with autologous dendritic-like leukaemia cells (DLLC). At trial entry,
      leukaemia cells were harvested and tested for their ability to undergo cytokine
      induced dendritic cell differentiation. Patients were then treated with intensive
      chemotherapy. Five patients achieved both CR and had leukaemia cells that
      successfully underwent differentiation and therefore proceeded to vaccination.
      Four escalating doses of DLLC were administered weekly by subcutaneous injection.
      Vaccination was generally well tolerated although one patient developed extensive
      eczema and an increased antinuclear factor titre possibly indicating induction of
      autoimmunity. Development of anti-leukaemic T-cell responses was assessed by
      enzyme-linked immunospot analysis of gamma-interferon secreting T lymphocytes and
      by human leucocyte antigen tetramer analysis for WT1-specific T cells. Increases
      in anti-leukaemic T-cell responses were demonstrated in four patients, but only
      two of the five remained in remission more than 12 months postvaccination. The
      study has demonstrated that generation of DLLC is feasible in only a subgroup of
      patients and is currently neither broadly applicable or clinically effective.

PMID- 16611306
TI  - Prognostic model for disease-specific and overall mortality in newly diagnosed
      symptomatic patients with Waldenstrom macroglobulinaemia.
AB  - We sought to define prognostic factors for survival in Waldenstrom
      macroglobulinaemia (WM). Of 585 patients diagnosed with WM and seen at Mayo
      Clinic between 1960 and 2001, 337 symptomatic patients met the inclusion criteria
      and were analysed for overall and disease-specific survival. The median survival
      from the time of diagnosis was 6.4 years. The median disease-specific survival
      was 11.2 years. Univariate analysis for overall survival identified the following
      adverse prognostic factors: age >65 years (P < 0.001), organomegaly (P < 0.001),
      elevated beta2-microglobulin (<0.001), anaemia (Hb < 10.0 g/dl) (P = 0.01),
      leucopenia (<4.0 x 10(9)/l) (P = 0.03), thrombocytopenia (<150 x 10(9)/l) (P =
      0.01), serum albumin <40 g/l (P = 0.001), and quantitative IgM < 0.4 g/l (P =
      0.04). On multivariate analysis, age >65 years and organomegaly were associated
      with poor prognosis. A prognostic model was built based on these two variables.
      Patients at high risk (1-2 risk factors, median survival 4.2 years) experienced
      worse survival than patients at low risk (0 risk factors, median survival 10.6
      years), P < 0.001. The prognostic model was validated in 204 patients who were
      not included in the analysis cohort. Beta2-microglobulin > or =4 mg/l was
      associated with a threefold increase in the risk of death when added to the
      prognostic model. We describe a simple prognostic model for overall survival for
      newly diagnosed patients with WM.

PMID- 16611307
TI  - Circulating levels and clinical significance of soluble CD86 in myeloma patients.
AB  - Circulating soluble CD86 (sCD86) levels are elevated in a number of leukaemias
      and are an independent prognostic factor in acute myeloid leukaemia. We
      investigated the clinical significance of circulating sCD86 in 299 patients from
      the UK Medical Research Council myeloma VIth trial, where patients received ABCM
      [adriamycin, carmustine (BCNU), cyclophosphamide, melphalan] either alone or with
      prednisolone (ABCM + P). Serum levels of sCD86 were significantly elevated (P =
      0.0001) in myeloma patients and using the median normal donor level (0.621 ng/ml)
      as a cut-off point, 70% of patients had elevated levels (range = 0.015-15.87
      ng/ml, median = 1.1 ng/ml). In univariate analysis elevated sCD86 levels were
      associated with significantly shorter (P < 0.001) survival (median = 22 vs. 51
      months) and event-free survival (median = 14 vs. 31 months) in ABCM + P but not
      ABCM patients. Multivariate analysis demonstrated that sCD86 was a significant,
      independent prognostic marker of both overall [risk ratio (RR) = 2.04, P =
      0.0006] and event-free (RR = 1.95, P = 0.0004) survival in ABCM + P patients. In
      conclusion, this study demonstrated that sCD86 levels are a significant
      independent prognostic marker in at least some myeloma treatment groups and its
      biological role and prognostic value should be further investigated.

PMID- 16611308
TI  - High incidence of myelodysplasia and secondary leukaemia in the UK Medical
      Research Council Pilot of autografting in chronic lymphocytic leukaemia.
AB  - We report a high incidence of myelodysplastic syndrome (MDS)/acute myeloid
      leukaemia (AML) in patients entered into the preceding Medical Research Council
      Chronic Lymphocytic Leukaemia Pilot study of autografting [corrected] Of 115
      newly diagnosed patients treated with fludarabine, 65 patients proceeded to
      autologous transplant. Conditioning was cyclophosphamide and total body
      irradiation in 49 (75%) patients and chemotherapy in 12 (18%). Ten patients have
      developed MDS/AML; eight had undergone an autograft. Five-year actuarial risk of
      developing MDS/AML postautograft was 12.4% (95% confidence interval, 2.5-24%). No
      analysed potential risk factor was predictive for MDS/AML development. We
      hypothesise that potential causative factors are fludarabine, low cell dose and
      transplant conditioning.

PMID- 16611309
TI  - Allogeneic haematopoietic stem cell transplantation in relapsed or refractory
      anaplastic large cell lymphoma of children and adolescents--a Berlin-Frankfurt
      Munster group report.
AB  - Patients with refractory or early relapsed anaplastic large cell lymphoma (ALCL)
      have a poor chance of survival. We report 20 children and adolescents with high
      risk relapsed or refractory ALCL who underwent allogeneic haematopoietic stem
      cell transplantation (HSCT). We retrospectively analysed 20 patients who relapsed
      between December 1991 and April 2003 during (six patients) or soon after first
      line Berlin-Frankfurt-Munster-type chemotherapy (14 patients) and underwent
      allogeneic HSCT. Nine patients received allogeneic HSCT after the first relapse
      and 11 after multiple relapses. Eight patients received their transplants from
      matched sibling donors, eight from unrelated donors and four from haploidentical
      family donors. The conditioning regimen was based on total body irradiation in 15
      patients. Two patients relapsed after allogeneic HSCT and died. Three patients
      died of transplant-related toxicity. Event-free survival at 3 years after
      allogeneic transplant was 75 +/- 10%. There was no influence of donor type or
      conditioning regimen on outcome. Two of six patients with progressive disease
      during frontline therapy survived compared with 13/14 patients with a first
      relapse after frontline therapy. Two of three patients who were transplanted with
      active lymphoma and all five patients who received allogeneic HSCT for relapse
      following autologous HSCT survived disease-free. Allogeneic HSCT is effective and
      has acceptable toxicity as rescue therapy for high-risk ALCL relapse. It even
      offers cure for patients refractory to chemotherapy, suggesting a graft-versus
      ALCL effect.

PMID- 16611310
TI  - The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the
      response to acenocoumarol in anticoagulated patients.
AB  - Much of the variability in the sensitivity to warfarin in anticoagulated patients
      is associated with the c.-1639G > A polymorphism of the vitamin K-epoxide
      reductase (VKORC1) gene. However, its association with the acenocoumarol dose in
      patients under anticoagulant therapy has not been studied. The c.-1639G > A
      genotype of VKORC1 was determined in 113 patients on stable anticoagulation
      requiring low (n = 42), medium (n = 42) or high (n = 21) acenocoumarol doses. To
      evaluate the association between acenocoumarol requirements and the c.-1639G > A
      variant, multivariate logistic regression models were fitted, adjusting for age,
      gender, and the c.430C > T and c.1075A > C variants of cytochrome P450 2C9
      (CYP2C9). A total of 90.5% of the patients in the low acenocoumarol dose group
      carried the A allele of VKORC1:c.-1639G > A. The A allele independently increased
      the odds of requiring a low acenocoumarol dose [odds ratio (OR) 9.4; 95%
      confidence interval (CI) 1.9-46.4; P = 0.006], especially when the homozygous
      form was present (OR 44.2; 95% CI 5.5-354.6; P < 0.001). The A allele was less
      frequent in the high dose group showing an inverse association with the
      requirement for high doses (OR 0.04; 95% CI 0.01-0.22; P < 0.001). The A allele
      of the c.-1639G > A polymorphism of VKORC1 is therefore associated with a low
      dose requirement for acenocoumarol in patients receiving anticoagulant therapy.

PMID- 16611311
TI  - Delayed diagnosis and complications of Fanconi anaemia at advanced age--a
      paradigm.
AB  - Fanconi anaemia (FA) is a rare recessive DNA repair disorder clinically
      characterised by congenital malformations, progressive bone marrow failure and a
      high propensity for developing malignancies at an early age, predominantly acute
      myeloid leukaemia (AML) and squamous cell carcinoma. It is conceivable that a
      number of patients with hypomorphic mutations are not diagnosed as FA until
      severe complications in the treatment of a malignancy occur. Here, we report on a
      patient with FA-A, diagnosed only at the age of 49 years due to persistent
      pancytopenia and myelodysplastic syndrome/AML induced by a first cycle of
      chemotherapy for bilateral metachronic breast cancer. This exceptional case
      clearly demonstrates that, in instances of long-lasting mild pancytopenia or
      development of malignancies, especially at an unusually young age, FA should be
      ruled out, irrespective of the patient's age and features, especially before
      inflicting severe genotoxic stress.

PMID- 16611312
TI  - Use of the oral chelator deferiprone in the treatment of iron overload in
      patients with Hb H disease.
AB  - Seventeen non-transfusion-dependent Chinese haemoglobin H (Hb H) disease patients
      (age 29-76 years) with serum ferritin >900 microg/l were treated with deferiprone
      for up to 18 months. One patient withdrew and data from 16 patients were
      analysed. Sixteen other Hb H patients with ferritin <900 microg/l, matched for
      age and genotype, acted as controls. Treatment was well tolerated except for mild
      arthralgia. Serum ferritin fell with treatment, reaching significance at 6 and 18
      months (from 1492.3 +/- 901.4 to 519.4 +/- 405.4 microg/l at 18 months, P =
      0.0008). Nine of 16 patients had levels below 397 microg/l before 18 months.
      Serum ferritin remained stable 6 months after stopping treatment. In contrast,
      there was no change in ferritin levels in the control group. Magnetic resonance
      imaging was used for measurement of liver iron content. Spin echo T(1)-signal
      intensity ratio (T(1)-SIR) and gradient echo T(2)-signal intensity ratio (T(2)
      SIR) increased with treatment. T(2)-SIR rose from 0.17 +/- 0.08 pretreatment to
      0.58 +/- 0.50 at 2 years (P = 0.0055). Improvement occurred in 12 of 16 patients,
      reaching normal in three patients. Using echocardiography, peak early diastolic :
      late diastolic blood flow (E/A) remained unchanged with treatment, but isovolumic
      relaxation time (IVRT) was prolonged at 2 years indicating mild impairment of
      diastolic function. All systolic function parameters were normal. A longer
      treatment period is desirable to demonstrate improvement in cardiac function.

PMID- 16611314
TI  - Stroke may appear to be rare in Saudi-Arabian and Nigerian children with sickle
      cell disease, but not in Cameroonian sickle cell patients.

PMID- 16611313
TI  - Co-inheritance of alpha+-thalassaemia and sickle trait results in specific
      effects on haematological parameters.
AB  - Both the sickle cell trait (HbAS) and alpha(+)-thalassaemia are common in many
      tropical areas. While their individual haematological effects are well described,
      few studies describe their effects when inherited together. We present data from
      the Kenyan coast, which suggest that HbAS and alpha(+)-thalassaemia may interact
      to produce specific effects on haematological parameters. Overall, the difference
      in Hb concentrations between non-thalassaemics (alphaalpha/alphaalpha) and
      alpha(+)-thalassaemia homozygotes (-alpha/-alpha) was greater in non-HbAS (HbAA)
      (0.63 g/dl) than in HbAS children (0.25 g/dl). HbAS also ameliorated both the
      reduced mean cell volume and mean cell haemoglobin normally associated with the 
      alpha/-alpha genotype. Potential mechanisms and implications are discussed.

PMID- 16611315
TI  - Temporal development of myeloma in a syngeneic twin pair.

PMID- 16611317
TI  - Positron emission tomography scans for distinguishing between osteomyelitis and
      infarction in sickle cell disease.

PMID- 16611318
TI  - The use of rituximab in two children with allo-antibodies towards factor VIII.

PMID- 16611319
TI  - Aspirin use in myeloma: a note of caution regarding potential tumour necrosis
      factor-alpha elevation.

PMID- 16611320
TI  - Co-stimulatory blockade--a pathway to tolerance?

PMID- 16611321
TI  - Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action.
AB  - Rituximab, chimeric anti-human CD20, is approved for treatment of B-cell lymphoma
      in adults. It is being used experimentally in other various immune-related
      diseases such as immune thrombocytopenic purpura, systemic lupus erythematosus,
      myasthenia gravis and rheumatoid arthritis. In transplant recipients, it is used
      for treatment of post-transplant lymphoproliferative disease, to anecdotally
      reduce pre-formed anti-HLA and anti-ABO antibodies and for the prevention and
      treatment of acute rejection. This article primarily reviews the science behind
      rituximab: its history, pharmacokinetics and potential mechanism of action. A
      need for controlled clinical trials is clearly indicated before the widespread
      use of this drug in transplant.

PMID- 16611322
TI  - Therapeutic targets in the treatment of allograft fibrosis.
AB  - The dramatic improvements in short-term graft survival and acute rejection rates
      could only have been dreamed of 20 years ago. Late graft loss following kidney
      transplantation is now the critical issue of this decade. Frequently, graft loss
      is associated with the development of tubular atrophy and interstitial fibrosis
      within the kidney (i.e. chronic allograft nephropathy; CAN). Major treatment
      strategies in this disorder are non-specific and the focus of intervention has
      been on limiting injurious events. Following graft injury is a fibrogenesis phase
      featuring both proliferative and infiltrative responses mediated by chemokines,
      cytokines and growth factors. In particular, TGFbeta has been strongly implicated
      in the pathogenesis of chronic injury and epithelial-mesenchymal transformation
      (EMT) may be part of this process. The cascade of events results in matrix
      accumulation, due to either increased production and/or reduced degradation of
      matrix. Recent investigations into the pathogenesis of tissue fibrosis have
      suggested a number of new strategies to ameliorate matrix synthesis. While the
      majority of therapies have focused on TGFbeta, this may not be an ideal maneuver
      in transplant settings and alternative targets identified in other fibrotic
      diseases will be discussed. Attacking graft fibrosis should be a new focus in
      organ transplantation.

PMID- 16611323
TI  - A new look at blockade of T-cell costimulation: a therapeutic strategy for long
      term maintenance immunosuppression.
AB  - Activated T cells orchestrate the immune response that results in graft
      rejection; therefore, a common goal among current immunosuppressive therapies is
      to block T-cell activation, proliferation and function. Current immunosuppressive
      regimens that inhibit T cells and immune cells have greatly reduced the incidence
      of acute rejection following solid-organ transplant. However, the expected
      improvements in long-term outcomes have not been realized. This may be related to
      the non-immune side effects of current maintenance immunosuppressants, which
      target ubiquitously expressed molecules. The focus in transplantation research is
      shifting in search of maintenance immunosuppressive regimens that might offer
      improved long-term outcomes by providing efficacy in prevention of acute
      rejection combined with reduced toxicities. An emerging therapeutic strategy
      involves an immunoselective maintenance immunosuppressant that inhibits full T
      cell activation by blocking the interaction between costimulatory receptor-ligand
      pairs. This review describes costimulatory pathways and the development of
      molecules, which inhibit them in the context of transplantation research. Recent
      clinical data using the selective costimulation blocker, belatacept (LEA29Y), as
      a part of a CNI-free maintenance immunosuppressive regimen in renal
      transplantation is highlighted.

PMID- 16611324
TI  - Transplant tolerance in non-human primates: progress, current challenges and
      unmet needs.
AB  - Given the significant morbidity associated with current post-transplant
      immunosuppressive regimens, induction of immune tolerance continues to be an
      important goal of clinical organ transplantation. While many strategies for
      inducing tolerance have been successfully applied in murine models, significant
      barriers are faced when translating these approaches to the clinic. This has
      necessitated pre-clinical studies in the more closely related model system, the
      non-human primates (NHP). In this review, we will discuss the four most prominent
      strategies for inducing transplantation tolerance and highlight their relative
      success and shortcomings in NHP. These strategies are: (1) T-cell costimulation
      blockade (2) mixed chimerism induction (3) T-cell depletion and (4) tolerance
      induction through regulatory T-cells. After discussing the progress that has been
      made with each of these strategies, we will identify this field's most pressing
      unmet needs and discuss how we may best overcome the resulting barriers to
      tolerance induction.

PMID- 16611325
TI  - Costimulation and autoimmune diabetes in BB rats.
AB  - Costimulatory signals regulate T-cell activation. To investigate the role of
      costimulation in autoimmunity and transplantation, we studied the BB rat model of
      type 1 diabetes. Diabetes-prone BB (BBDP) rats spontaneously develop disease when
      55-120 days of age. We observed that two anti-CD28 monoclonal antibodies (mAb)
      with different functional activities completely prevented diabetes in BBDP rats.
      Anti-CD154 mAb delayed diabetes, whereas treatment with CTLA4-Ig or anti-CD80 mAb
      accelerated disease. Anti-CD86 or anti-CD134L mAbs had no effect. Diabetes
      resistant BB (BBDR) rats are disease-free, but >95% of them develop diabetes
      after treatment with polyinosinic-polycytidylic acid and an mAb that depletes
      Treg cells. In the induced BBDR model, anti-CD154 mAb delayed onset of diabetes,
      whereas CTLA4-Ig, anti-CD134L or either of the anti-CD28 mAbs had little or no
      effect. In contrast, blockade of the CD134-CD134L pathway was highly effective
      for preventing autoimmune recurrence against syngeneic islet grafts in diabetic
      BBDR hosts. Blockade of the CD40-CD154 pathway was also effective, but less so.
      These data suggest that the effectiveness of costimulation blockade in the
      treatment of type 1 diabetes is dependent on both the costimulatory pathway
      targeted and the mechanism of induction, stage, intensity and duration of the
      pathogenic process.

PMID- 16611326
TI  - Rescue of the cold preserved rat liver by hypothermic oxygenated machine
      perfusion.
AB  - The aim of the study was to investigate whether hypothermic oxygenated liver
      perfusion after cold liver preservation resuscitated metabolic parameters and
      whether this treatment had a benefit for liver viability upon reperfusion. We
      preserved rat livers either by cold storage (UW) for 10 h, or by perfusion for 3
      h (oxygenated modified UW) after 10 h cold storage. We assessed viability of
      livers after preservation and after ischemic rewarming+normothermic reperfusion
      ex vivo. Ten hour cold storage reduced mitochondrial cytochrome oxidase and
      metabolically depleted the livers. Oxygenated perfusion after cold storage
      resulted in uploaded cellular energy charge and oxidized mitochondrial cytochrome
      oxidase. Reperfusion after 10 h cold storage increased formation of superoxid
      anions, release of cytosolic LDH, lipid peroxidation, caspase activities and led
      to disruption of sinusoidal endothelial cells. In contrast, reperfusion after 10
      h cold storage+3 h hypothermic oxygenated perfusion resulted in no changes of
      lipid peroxidation, bile flow, energy charge, total glutathione, LDH release and
      of caspase activation, as compared to fresh resected livers. This study
      demonstrates, that a metabolically depleted liver due to cold storage can be
      energy recharged by short-termed cold machine perfusion. The machine perfused
      graft exhibited improved viability and functional integrity.

PMID- 16611327
TI  - A mouse model for polyomavirus-associated nephropathy of kidney transplants.
AB  - Polyomavirus-associated nephropathy is an important cause of dysfunction and
      failure of renal transplants. BK virus is an ubiquitous human polyoma virus that
      persistently infects the kidney. This otherwise silent infection can reactivate
      in immunosuppressed individuals, resulting in renal complications. Because
      polyoma viruses are highly species-specific, we developed a mouse polyoma virus
      renal transplant model in order to investigate the pathogenesis of polyomavirus
      associated nephropathy. Using this model, we found that polyoma virus
      preferentially replicates in the allogeneic kidney grafts, accelerating graft
      failure; thus, this animal model is able to mimic the polyomavirus-associated
      nephropathy seen in human renal transplant patients. Acute polyoma virus
      infection of mouse allograft recipients augmented the alloreactive CD8+ T-cell
      response, while maintaining the anti-viral CD8+ T-cell response. In addition to
      the known virus-induced cytopathology, these findings demonstrate a potential
      role for an enhanced anti-donor T-cell response in the pathogenesis of
      polyomavirus-associated nephropathy.

PMID- 16611328
TI  - C4d deposition and clearance in cardiac transplants correlates with alloantibody
      levels and rejection in rats.
AB  - Antibody-mediated rejection of human cardiac transplants is correlated with C4d
      deposits and macrophage infiltrates in capillaries of endomyocardial biopsies. We
      produced an antibody to rat C4d to study C4d deposition and clearance in Lewis
      rats that were sensitized with a blood transfusion from DA rats 7, 14 or 21 days
      before cardiac transplantation. Cyclosporin A (CsA) immunosuppression was
      initiated after transplantation at a dose that inhibited graft rejection,
      antibody production and C4d deposition in unsensitized recipients. Blood
      transfusion elicited high levels of circulating IgG alloantibodies, predominantly
      of the complement-activating IgG2b subclass, that peaked 14 days after
      transplantation. At this time, macrophages accumulated in capillaries, and C4d
      deposits were diffuse and intense on arteries, capillaries and veins. Grafts that
      survived 90 days in sensitized recipients still had deposits of C4d that were
      associated with increased interstitial fibrosis and vasculopathy in arteries.
      Clearance of C4d was determined by retransplanting DA cardiac allografts from
      Lewis recipients back to DA recipients. C4d deposits were decreased to minimal
      levels within 5 days after retransplantation. Thus, C4d deposition is not limited
      to the capillaries, but extends throughout the arterial tree, and despite
      formation of a covalent bond, C4d is cleared within days.

PMID- 16611329
TI  - Increasing donor chimerism and inducing tolerance to islet allografts by post
      transplant donor lymphocyte infusion.
AB  - Inducing donor chimerism is the most consistently successful approach to achieve
      transplant tolerance. We found that a low level of donor chimerism, which was
      induced by a relatively non-toxic approach, induced donor-specific tolerance to
      islet allografts in chemically induced diabetic mice. However, a similar level of
      donor chimerism could not protect donor islet allografts in non-obese diabetic
      (NOD) mice that spontaneously developed autoimmune diabetes. Rejection of donor
      islet allografts in diabetic NOD mice with a low level of donor chimerism was
      mediated by recurrent autoimmunity. We used post-transplant donor lymphocyte
      infusion (DLI) to increase donor chimerism and to induce tolerance to islet
      allografts. DLI significantly increased donor chimerism and promoted donor
      specific tolerance to islet allografts in diabetic NOD mice. Self-tolerance to
      islet autoantigens was restored and restoring self-tolerance is mediated by
      immunoregulation. Thus, our data showed that adoptive immunotherapy with post
      transplant DLI after establishing a low level of donor chimerism as a platform
      enhances donor chimerism, induces donor-specific tolerance to islet allografts
      and restores self-tolerance in the setting of autoimmune diabetes. Our data also
      showed that central tolerance is not sufficient to induce tolerance and
      peripheral tolerance through immunoregulation for restoring self-tolerance is
      required in the setting of autoimmune diabetes.

PMID- 16611330
TI  - Multipotent cells of monocytic origin improve damaged heart function.
AB  - Recently, we generated cells with multipotent properties from blood monocytes
      that in vitro differentiate into various somatic cell types. This experimental
      study investigated whether these programmable cells of monocytic origin (PCMO)
      succeed to restore left ventricular function after myocardial infarction (MI).
      PCMO were generated from monocytes by exposition to RPMI medium containing M-CSF
      and IL-3 for 6 days. MI was induced in female Lewis rats ligating the left
      coronary artery. PCMO of male Lewis donors were injected either intramyocardially
      (i.my.) or intravenously (i.v.) 24 h or 6 days post-infarction. Hemodynamic
      assessment after 60 days demonstrated significant improvement of left ventricular
      function following i.my. transplantation of PCMO as well as early (24 h post
      infarction) i.v. application while nonmodulated monocytes failed to restore heart
      function. The Y-chromosome-specific SRY gene of male donor PCMO was detected
      exclusively in infarcted hearts of animals, which demonstrated improved cardiac
      function. Subdivision of infarcted hearts by microdissection localized the SRY
      gene-containing department to the left ventricle adjacent to the infarcted area
      whereas the right ventricle remained negative. Successful generation of PCMO in
      access numbers allows their autologous use as a new additive treatment for early
      restoration of cardiac function after MI.

PMID- 16611331
TI  - Transforming growth factor beta-induced connective tissue growth factor and
      chronic allograft rejection.
AB  - Late loss of allograft function is primarily attributed to chronic rejection
      (CR). There are no effective treatments for CR and the underlying cause of the
      disease is unknown. This study compared events that occurred within cardiac
      allografts placed in mice that received either anti-CD4 therapy and develop CR or
      anti-CD40L therapy and do not develop CR. Both TGFbeta and connective tissue
      growth factor (CTGF), which is induced by TGFbeta, were expressed in grafts with
      CR but were not expressed in grafts without CR. TGFbeta transfection of
      allografts in anti-CD40L-treated recipients resulted in CTGF expression and CR.
      However, TGFbeta transfection of syngeneic grafts did not result in CTGF
      expression or CR. These data indicate that TGFbeta alone is insufficient to
      induce CR and that CTGF is required. Further, antigenic stimulation is required
      for TGFbeta induction of CTGF. Thus, CTGF may serve as a therapeutic target for
      CR.

PMID- 16611332
TI  - Islets transplanted intraportally into the liver are stimulated to insulin and
      glucagon release exclusively through the hepatic artery.
AB  - Not much is known about the physiology of intraportally transplanted islets. One
      reason for this is that it is difficult to study such islets, since they are
      scattered throughout the liver. We employed a perfusion technique to characterize
      the functional properties of syngeneic intrahepatic 1-month-old islet grafts, and
      compared them to islets transplanted beneath the kidney capsule, as well as
      native islets. The cellular composition of the islet grafts was also examined.
      Glucose and arginine administered through the hepatic artery, but not through the
      portal vein, induced insulin release from the intraportally implanted islets.
      Moreover, arginine, only when administered through the hepatic artery, induced
      glucagon release from the same islets. The first phase of glucose-stimulated
      insulin release from both islets transplanted to the liver and kidney was
      delayed, and less prominent when compared to the pancreas. Intraportally
      transplanted islets contained fewer glucagon-positive cells than islets
      transplanted to the kidney and native islets. Our findings demonstrate that
      intraportally transplanted islets respond with insulin and glucagon to
      secretagogues, but only when stimulated through the hepatic artery. Whether
      intrahepatic islets may sense other substances than glucose or arginine occurring
      in high concentrations in the portal vein following intestinal uptake remains to
      be studied.

PMID- 16611333
TI  - EBV B lymphoma cell lines from patients with post-transplant lymphoproliferative
      disease are resistant to TRAIL-induced apoptosis.
AB  - Lymphomas associated with post-transplant lymphoproliferative disease (PTLD)
      represent a significant complication of immunosuppression in transplant
      recipients. In immunocompetent individuals, EBV-specific cytotoxic T lymphocytes
      (CTL) prevent the outgrowth of activated B lymphoblasts through apoptosis
      induction. Soluble versions of TNF-related apoptosis-inducing ligand/Apo2 ligand
      (TRAIL) can induce apoptosis in numerous tumor cell types. Given the therapeutic
      potential of TRAIL, we examined the sensitivity of EBV+ spontaneous
      lymphoblastoid cell lines (SLCL) derived from patients with PTLD to treatment
      with soluble TRAIL. Despite abundant expression of TRAIL receptors (TRAIL-R),
      resistance to TRAIL-induced apoptosis was observed in all SLCL examined. This
      resistance could not be overcome by concomitant treatment with several
      pharmacological agents. Unlike BJAB positive control cells, for each SLCL tested,
      cleavage and activation of caspase 8 was inhibited due to failed recruitment of
      FADD and caspase 8 to TRAIL receptors upon stimulation. Further indicative of a
      proximal defect, TRAIL receptor aggregation could not be detected on the cell
      surface of SLCL following ligand engagement. These results suggest that the use
      of TRAIL for eliminating PTLD-associated tumors may be of limited clinical
      utility, and illustrate another mechanism by which EBV+ B lymphoma cells can
      evade tumor surveillance at the level of death receptor signaling.

PMID- 16611334
TI  - Wound healing complications with de novo sirolimus versus mycophenolate mofetil
      based regimen in cardiac transplant recipients.
AB  - Sirolimus was introduced in de novo immunosuppression at Stanford University in
      view of its favorable effects on reduced rejection and cardiac allograft
      vasculopathy. After an apparent increase in the incidence of post-surgical wound
      complications as well as symptomatic pleural and pericardial effusions, we
      reverted to a mycophenolate mofetil (MMF)-based regimen. This retrospective study
      compared the outcome in heart transplant recipients on sirolimus (48 patients)
      with those on MMF (46 patients) in de novo immunosuppressive regimen. The
      incidence of any post-surgical wound complication (52% vs. 28%, p=0.019) and deep
      surgical wound complication (35% vs. 13%, p=0.012) was significantly higher in
      patients on sirolimus than on MMF. More patients on sirolimus also had
      symptomatic pleural (p=0.035) and large pericardial effusions (p=0.033) requiring
      intervention. Logistic regression analysis showed sirolimus (p=0.027) and longer
      cardiac bypass time (OR=1.011; p=0.048) as risk factors for any wound
      complication. Sirolimus in de novo immunosuppression after cardiac
      transplantation was associated with a significant increase in the incidence of
      post-surgical wound healing complications as well as symptomatic pleural and
      pericardial effusions.

PMID- 16611335
TI  - Mycophenolate mofetil reduces intimal thickness by intravascular ultrasound after
      heart transplant: reanalysis of the multicenter trial.
AB  - The mycophenolate mofetil (MMF) trial involved 650 heart transplant patients from
      28 centers who received MMF or azathioprine (AZA), both in combination with
      cyclosporine and corticosteroids. Baseline and 1-year intravascular ultrasound
      (IVUS) were performed in 196 patients (102 MMF and 94 AZA) with no differences
      between groups in IVUS results analyzed by morphometric analysis (average of 10
      evenly spaced sites, without matching sites between studies). Baseline to first
      year IVUS data can also be analyzed by site-to-site analysis (matching sites
      between studies), which has been reported to be more clinically relevant.
      Therefore, we used site-to-site analysis to reanalyze the multicenter MMF IVUS
      data. RESULTS: IVUS images were reviewed and interpretable in 190 patients (99
      MMF and 91 AZA) from the multicenter randomized trial. The AZA group compared to
      the MMF group had a larger number of patients with first-year maximal intimal
      thickness (MIT)>or=0.3 mm (43% vs. 23%, p=0.005), a greater decrease in the mean
      lumen area (p=0.02) and a decrease in the mean vessel area (the area actually
      increased in the MMF group, p=0.03). CONCLUSION: MMF-treated heart transplant
      patients compared to AZA-treated patients, both concurrently on cyclosporine and
      corticosteroids, in this study have significantly less progression of first-year
      intimal thickening.

PMID- 16611336
TI  - Coronary flow reserve by contrast-enhanced echocardiography: a new noninvasive
      diagnostic tool for cardiac allograft vasculopathy.
AB  - Noninvasive tests have proven unsatisfactory in cardiac allograft vasculopathy
      (CAV) diagnosis. We assessed coronary flow reserve (CFR) by contrast-enhanced
      transthoracic echocardiography (CE-TTE) in heart transplantation (HT). CFR was
      assessed in the left anterior descending coronary artery in 73 HT recipients (59
      male, aged 50+/-12 years at HT), at 8+/-4.5 years post-HT. CFR measurements were
      taken blindly from coronary angiographies. CFR cut points were the standard value
      of <or=2 and those defined by receiver operating characteristics (ROC) curve
      analysis. CFR was lower in patients with CAV (2.3+/-0.7 vs. 3.2+/-0.5, p<0.0001).
      The <or=2 cut point was 100% specific and 38% sensitive. The <or=2.7 cut point,
      optimal by ROC analysis, was 87% specific and 82% sensitive. Accuracy rose from
      71% with the standard<or=2 cut point to 85% with the optimal cut point of
      <or=2.7. CFR by CE-TTE may offer promise as a novel, easily repeatable and
      accurate noninvasive tool in CAV detection. However, further longitudinal studies
      in larger patient cohorts are warranted before widespread adoption can be
      advocated.

PMID- 16611337
TI  - Feasibility of left lobe living donor liver transplantation between adults: an 8
      year, single-center experience of 107 cases.
AB  - Operative mortality for a right lobe (RL) donor in adult living donor liver
      transplantation (LDLT) is estimated to be as high as 0.5-1%. To minimize the risk
      to the donor, left lobe (LL)-LDLT might be an ideal option in adult LDLT. The aim
      of the study was to assess the feasibility of LL-LDLT between adults based on a
      single-center experience of 107 LL-LDLTs performed over 8 years. The mean graft
      weight of LL grafts was 452 g, which amounted to 40.5% of the estimated standard
      liver volume of the recipients. The overall 1-, 3- and 5-year patient survival
      rates in LL-LDLT were 81.4, 76.9 and 74.7%, respectively, which were comparable
      to those of RL-LDLT. Twenty-six grafts (24.3%) were lost for various reasons with
      three losses directly attributable to small-for-size graft syndrome. Post
      operative liver function and hospital stay in LL donors were significantly better
      and shorter than that in RL donors, while the incidence of donor morbidity was
      comparable between LL and RL donors. In conclusion, LL-LDLT was found to be a
      feasible option in adult-to-adult LDLT. Further utilization of LL grafts should
      be undertaken to keep the chance of donor morbidity and mortality minimal.

PMID- 16611338
TI  - Segmental liver transplantation from non-heart beating donors--an early
      experience with implications for the future.
AB  - We report our experience of pediatric liver transplantation with partial grafts
      from non-heart beating donors (NHBD). Controlled donors less than 40 years of age
      with a warm ischemia time (WI) of less than 30 min were considered for pediatric
      recipients. Death was declared 5 min after asystole. A super-rapid recovery
      technique with aortic and portal perfusion was utilized. Mean donor age was 29
      years and WI 14.6 min (range 11-18). Seven children, mean age 4.9 years (0.7-11),
      median weight 20 kg (8.4-53) received NHBD segmental liver grafts. Diagnoses
      included seronegative hepatitis, neonatal sclerosing cholangitis, familial
      intrahepatic cholestasis, hepatoblastoma, primary hyperoxaluria and factor VII
      deficiency (n=2). The grafts included four reduced and one split left lateral
      segments, one left lobe and one right auxiliary graft. Mean cold ischemia was 7.3
      h (6.2-8.8). Complications included one pleural effusion and one biliary
      collection drained percutaneously. At 20 months (10-36) follow-up all children
      are alive and well with functioning grafts. Donation after cardiac death is a
      significant source of liver grafts for adults and children with careful donor
      selection and short cold ischemic times.

PMID- 16611339
TI  - Post-transplant lymphoproliferative disorders following liver transplantation:
      incidence, risk factors and survival.
AB  - This study investigates retrospectively the incidence, risk factors and mortality
      of post-transplant lymphoproliferative disorders (PTLD) in adult orthotopic liver
      transplant (OLT) recipients. Among 1206 OLT recipients at a single institution,
      37 developed a PTLD. The incidence of PTLD was highest during the first 18 months
      and relatively constant thereafter with cumulative incidence of 1.1% at 18 months
      and 4.7% at 15 years. The risk of PTLD was approximately 10% to 15% of the risk
      of death without PTLD. During the first 4 years following OLT, PTLD were
      predominantly related to EBV, while afterward most PTLD were EBV negative.
      Significant risk factors for PTLD in OLT recipients were transplantation for
      acute fulminant hepatitis during the first 18 months following OLT (HR=2.6,
      p=0.007), and rejection therapy with high-dose steroids (HR=4.5, p=0.049) and
      OKT3 (HR=3.9, p=0.016) during the previous year. Therapy with high-dose steroids
      or OKT3 (HR=3.6, p=0.0071) were also significant risk factors for PTLD-associated
      mortality. OLT recipients remain at risk for PTLD years after transplantation.
      The strong association of PTLD with rejection therapy and the worse post-PTLD
      prognosis among recipients of rejection therapy indicate the need to balance the
      risk of immunosuppression against the risk of PTLD following rejection treatment.

PMID- 16611340
TI  - Kidney transplant function and histological clearance of virus following
      diagnosis of polyomavirus-associated nephropathy (PVAN).
AB  - Polyomavirus-associated nephropathy (PVAN) is managed by reduced
      immunosuppression with or without antiviral therapy. Data from 55 patients with
      biopsy-proven PVAN were analyzed for adverse outcomes and influence of baseline
      variables and interventions. During 20+/-11 months follow-up, the frequencies of
      graft loss, major and any functional decline were 15%, 24% and 38%, respectively.
      Repeat biopsies were performed in 45 patients with persistent PVAN in 47%. Low
      dose cidofovir, IVIG and cyclosporine conversion were used in 55%, 20% and 55% of
      patients. No single intervention was associated with improved outcome. Of the
      variables examined, only degree of interstitial fibrosis at diagnosis was
      associated with kidney function decline. In contrast, donor source, interstitial
      fibrosis, proportion of BKV positive tubules and plasma viral load at diagnosis
      were all associated with failure of histological viral clearance. This
      retrospective, nonrandomized analysis suggests that: (i) Graft loss within 2
      years of PVAN diagnosis is now uncommon, but ongoing functional decline and
      persistent infection occur frequently. (ii) Low-dose cidofovir, IVIG and
      conversion to cyclosporine do not abrogate adverse outcomes following diagnosis.
      (iii) Fibrosis at the time of diagnosis predicts subsequent functional decline.
      Further elucidation of the natural history of PVAN and its response to individual
      interventions will require prospective clinical trials.

PMID- 16611341
TI  - Pivotal role of complement-fixing HLA alloantibodies in presensitized kidney
      allograft recipients.
AB  - Recipient presensitization represents a major risk factor for kidney allograft
      loss. Complement fixation may be a critical attribute of deleterious
      alloantibodies. We investigated clinical impact of complement-fixing HLA
      presensitization employing [C4d]FlowPRA, a novel assay permitting selective
      detection of HLA panel reactive antibody (PRA)-triggered C4 complement split
      product deposition. A cohort of 338 kidney transplants was evaluated for
      presensitization applying [C4d]FlowPRA together with [IgG]FlowPRA and complement
      dependent cytotoxicity (CDC)-PRA. Analysis of HLA class I alloreactivities
      revealed a high incidence of C4d-positive graft dysfunction in
      [IgG]FlowPRA(+)/[C4d]FlowPRA(+) and [IgG]FlowPRA(+)/[C4d]FlowPRA(-) recipients
      (23% and 22% vs. 3% in [IgG]FlowPRA(-) patients). Only patients with complement
      fixing HLA class I immunization had inferior graft survival [75% (3 years) vs.
      91% and 89%, respectively (p=0.036)]. Despite frequent finding of capillary C4d
      deposition (28%), complement-fixing HLA class II immunization was not associated
      with inferior survival rates. This may have been due to reduction of clinical
      effects by intense immunosuppression in presensitized patients. Evaluating CDC,
      29% of CDC-PRA(+)/[C4d]FlowPRA(+) recipients had C4d-positive graft dysfunction.
      For these patients 3-year graft survival was worst, followed by CDC
      PRA(+)/[C4d]FlowPRA(-) and CDC-PRA(-) patients (76% vs. 81% vs. 90%, p=0.014).
      Results highlight a strong impact of complement-fixing HLA presensitization.
      Discerning complement-activating abilities of HLA alloantibodies, [C4d]FlowPRA
      may help identify recipients at particularly high risk for graft rejection and
      loss.

PMID- 16611342
TI  - Impact of early or delayed cyclosporine on delayed graft function in renal
      transplant recipients: a randomized, multicenter study.
AB  - The benefit of delayed cyclosporine in reducing risk of delayed graft function
      (DGF) is not clearly established. This study compared early vs. delayed
      cyclosporine microemulsion (CsA-ME) inde novorenal transplant patients. Patients
      were randomized to early (day 0, n=97) or delayed (day 6, n=100) CsA-ME at an
      initial dose of 8 mg/kg/day with dose adjusted according to C2 level. All
      patients received enteric-coated mycophenolate sodium (EC-MPS), steroids and an
      anti-interleukin-2 receptor antibody. In both groups, 33% of patients were at
      high risk of DGF; 26 patients (26.8%) in the early CsA-ME group and 23 patients
      (23.0%) in the delayed CsA-ME group experienced DGF (n.s.). Renal function at 3
      months was comparable (creatinine clearance 51.1 mL/min with early CsA-ME and
      53.8 mL/min with delayed CsA-ME), and remained similar to 12 months. Treatment
      failure, defined as biopsy-proven acute rejection, graft loss or death, did not
      differ significantly at 12 months (23.7% with early CsA-ME vs. 29.0% with delayed
      CsA-ME). Biopsy-proven acute rejection occurred in 15.5% of early CsA-ME and
      26.5% of delayed CsA-ME patients (n.s.). Both regimens were well tolerated. These
      data suggest that early or delayed introduction of CsA-ME results in similar
      renal function in renal transplant patients regardless of DGF risk level.

PMID- 16611344
TI  - Outcomes of pancreas transplantation in the United States using cardiac-death
      donors.
AB  - Organs donated after cardiac death (DCD) are used to expand the donor pool. We
      analyzed the outcomes in the United States of pancreatic transplantation of
      organs from DCD donors performed between 1993 and 2003. We used the OPTN/UNOS
      Registry to compare outcomes of primary pancreas allografts from DCD donors and
      donors after brain death (DBD). The primary endpoints were graft failure and
      patient death. A national survey regarding the use of DCD donors in pancreas
      transplantation was conducted among the directors of pancreas transplant centers.
      Data were obtained on 47 simultaneous pancreas-kidney transplants (SPK) and 10
      solitary pancreas transplants from DCD donors and on 2431 SPK and 1607 solitary
      pancreas transplants from DBD donors. Recipients of a SPK transplants from DCD
      and DBD donors had equivalent patient and graft survival rates at 1, 3 and 5
      years. For recipients of SPK transplants, the wait for organs from DCD donors was
      significantly shorter than that for organs from DBD donors. SPK recipients of
      organs from DCD donors had longer hospital stays than did recipients of organs
      from DBD donors. With renal allografts, the incidence of delayed graft function
      was almost four times higher with organs from DCD donors than with organs from
      DBD donors. Selective use of organs from DCD donors is safe for pancreas
      transplantation.

PMID- 16611343
TI  - Sequential kidney/islet transplantation: efficacy and safety assessment of a
      steroid-free immunosuppression protocol.
AB  - The aim of this study was to assess the efficiency and safety of the Edmonton
      immunosuppression protocol in recipients of islet-after-kidney (IAK) grafts.
      Fifteen islet infusions were administered to 8 patients with type 1 diabetes and
      a functioning kidney graft. Immunosuppression was switched on the day of
      transplantation to a regimen associating sirolimus-tacrolimus-daclizumab. Insulin
      independence was achieved in all patients for at least 3 months, with an actual
      rate of 71% at 1 year after transplantation (5 of 7 patients). After 24-month
      mean follow-up, five have ongoing insulin independence, 11-34 months after
      transplantation, with normal HbA1c, fructosamine and mean amplitude of glycemic
      excursions (MAGE) values. Results of arginine-stimulation tests improved over
      time, mostly after the second islet infusion. Severe adverse events included
      bleeding after percutaneous portal access (n=2), severe pneumonia attributed to
      sirolimus toxicity (n=1), kidney graft loss after immunosuppression
      discontinuation (n=1), reversible humoral kidney rejection (n=1) and fever of
      unknown origin (n=1). These data indicate that the Edmonton approach can be
      successfully applied to the IAK setting. This procedure is associated with
      significant side effects and only patients with stable function of the kidney
      graft should be considered. The net harm versus benefit has not yet been
      established and will require further studies with larger numbers of enrolled
      subjects.

PMID- 16611345
TI  - Kidney transplantation using elderly non-heart-beating donors: a single-center
      experience.
AB  - Although acceptable outcomes have been reported in both non-heart-beating (NHB)
      and elderly donors individually, the large pool of elderly NHB donors has not yet
      been fully utilized. In 1994, we expanded our transplant protocol to include NHB
      donors aged over 65 years and this study compares the clinical outcomes with
      regular NHB transplantations. Up to June 2005, 24 patients were transplanted at
      our center with kidneys from NHB donors aged 65 years or more, whereas 176
      patients received grafts from conventional NHB donors during the same period.
      Grafts from older donors were associated with inferior glomerular filtration
      rates (29 vs. 44 mL/min after 1 year, p=0.01) and graft survival (52% vs. 68%
      after 5 years, p=0.19) compared to younger NHB donor grafts, although the
      difference in graft survival was not statistically significant. Exclusion of
      older NHB donor kidneys with severe vascular pathology resulted in similar graft
      survival of older and younger NHB donor kidneys. We conclude that the use of
      elderly NHB donors in order to expand the donor pool was associated with
      unacceptable clinical outcomes and cannot be justified without further refinement
      in their selection, for example, by histological assessment of pretransplant
      biopsies.

PMID- 16611346
TI  - Severe dysimmune cytopenia in children treated with tacrolimus after organ
      transplantation.
AB  - Rare cases of dysimmune phenomena after solid organ transplantation were
      described in the past. In the present series, we describe six children who
      developed severe dysimmune anemia or thrombocytopenia while treated with
      tacrolimus after liver or small bowel transplantation. All patients were off
      steroids or under low doses alternate day steroid medication when dysimmune
      cytopenia developed. All patients had positive anti-platelets antibodies and/or
      Coombs' positive anemia. Therapy was successful in all six patients with a rapid
      response to corticosteroids in three children, and to anti-CD20 monoclonal
      antibodies (rituximab) in the three others. The pathogenesis of these rare
      dysimmune/autoimmune disorders might be related to the interference of tacrolimus
      with T-cell functions and/or the endogenous control mechanisms of T-lymphocyte
      activation and down-regulation. Although rare, these complications must be known
      when discussing protocols of immunosuppression.

PMID- 16611347
TI  - Case report of lamivudine-resistant hepatitis B virus infection post liver
      transplantation from a hepatitis B core antibody donor.
AB  - The use of allografts from donors with hepatitis B core antibody in liver
      transplantation (LT) is associated with the risk of de novo hepatitis B virus
      (HBV) infection. Prophylaxis using hepatitis B Immune globulin (HBIg) and
      lamivudine alone or in combination has been reported. Yet, there are no
      standardized regimens and long-term efficacy is not known. We report a case of a
      patient who underwent LT for alcoholic liver disease who received an allograft
      from a donor with Hepatitis B core antibody. The patient had no previous exposure
      to HBV, was vaccinated against HBV, and had demonstrated Hepatitis B surface
      antibody present in serum before and 6 months after transplantation. Prophylaxis
      with short-term HBIg (1 week) and indefinite lamivudine was given. De novo HBV
      infection developed more than 3 years after LT with a lamivudine-resistant
      polymerase mutant containing the rtM204I and rtl180L/M mutations. We reviewed the
      risk of de novo post-LT HBV infection in recipients of livers from hepatitis B
      core antibody positive donors. High risk were HBV naive recipients, moderate risk
      recipients had isolated hepatitis B surface antibody (anti-HBs) or hepatitis B
      core antibody (anti-HBc), while low-risk recipients had both anti-HBs and anti
      HBc. We reviewed prophylaxis protocols reported in the literature and made
      recommendations for management.

PMID- 16611348
TI  - Autoimmune thyroid disease after renal transplantation using depletional
      induction with alemtuzumab.

PMID- 16611349
TI  - Methodological challenges of genomic research--the CARGO study.

PMID- 16611350
TI  - Injuries incurred during laparoscopic donor nephrectomy with the endocatch
      recovery system.

PMID- 16611353
TI  - 26th International Symposium on Intensive Care and Emergency Medicine. Brussels,
      Belgium. 21 - 24 March 2006. Abstracts.

PMID- 16611351
TI  - Cytomegalovirus infection in a recipient of solitary allogeneic islets.

PMID- 16611354
TI  - Integrative investigation of metabolic and transcriptomic data.
AB  - BACKGROUND: New analysis methods are being developed to integrate data from
      transcriptome, proteome, interactome, metabolome, and other investigative
      approaches. At the same time, existing methods are being modified to serve the
      objectives of systems biology and permit the interpretation of the huge datasets
      currently being generated by high-throughput methods. RESULTS: Transcriptomic and
      metabolic data from chemostat fermentors were collected with the aim of
      investigating the relationship between these two data sets. The variation in
      transcriptome data in response to three physiological or genetic perturbations
      (medium composition, growth rate, and specific gene deletions) was investigated
      using linear modelling, and open reading-frames (ORFs) whose expression changed
      significantly in response to these perturbations were identified. Assuming that
      the metabolic profile is a function of the transcriptome profile, expression
      levels of the different ORFs were used to model the metabolic variables via
      Partial Least Squares (Projection to Latent Structures--PLS) using PLS toolbox in
      Matlab. CONCLUSION: The experimental design allowed the analyses to discriminate
      between the effects which the growth medium, dilution rate, and the deletion of
      specific genes had on the transcriptome and metabolite profiles. Metabolite data
      were modelled as a function of the transcriptome to determine their congruence.
      The genes that are involved in central carbon metabolism of yeast cells were
      found to be the ORFs with the most significant contribution to the model.

PMID- 16611355
TI  - Planning a cluster randomized trial with unequal cluster sizes: practical issues
      involving continuous outcomes.
AB  - BACKGROUND: Cluster randomization design is increasingly used for the evaluation
      of health-care, screening or educational interventions. At the planning stage,
      sample size calculations usually consider an average cluster size without taking
      into account any potential imbalance in cluster size. However, there may exist
      high discrepancies in cluster sizes. METHODS: We performed simulations to study
      the impact of an imbalance in cluster size on power. We determined by simulations
      to which extent four methods proposed to adapt the sample size calculations to a
      pre-specified imbalance in cluster size could lead to adequately powered trials.
      RESULTS: We showed that an imbalance in cluster size can be of high influence on
      the power in the case of severe imbalance, particularly if the number of clusters
      is low and/or the intraclass correlation coefficient is high. In the case of a
      severe imbalance, our simulations confirmed that the minimum variance weights
      correction of the variation inflaction factor (VIF) used in the sample size
      calculations has the best properties. CONCLUSION: Publication of cluster sizes is
      important to assess the real power of the trial which was conducted and to help
      designing future trials. We derived an adaptation of the VIF from the minimum
      variance weights correction to be used in case the imbalance can be a priori
      formulated such as "a proportion (gamma) of clusters actually recruit a
      proportion (tau) of subjects to be included (gamma < or = tau)".

PMID- 16611356
TI  - In vivo-in vitro toxicogenomic comparison of TCDD-elicited gene expression in
      Hepa1c1c7 mouse hepatoma cells and C57BL/6 hepatic tissue.
AB  - BACKGROUND: In vitro systems have inherent limitations in their ability to model
      whole organism gene responses, which must be identified and appropriately
      considered when developing predictive biomarkers of in vivo toxicity. Systematic
      comparison of in vitro and in vivo temporal gene expression profiles were
      conducted to assess the ability of Hepa1c1c7 mouse hepatoma cells to model
      hepatic responses in C57BL/6 mice following treatment with 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). RESULTS: Gene expression analysis and
      functional gene annotation indicate that Hepa1c1c7 cells appropriately modeled
      the induction of xenobiotic metabolism genes in vivo. However, responses
      associated with cell cycle progression and proliferation were unique to Hepa1c1c7
      cells, consistent with the cell cycle arrest effects of TCDD on rapidly dividing
      cells. In contrast, lipid metabolism and immune responses, representative of
      whole organism effects in vivo, were not replicated in Hepa1c1c7 cells.
      CONCLUSION: These results identified inherent differences in TCDD-mediated gene
      expression responses between these models and highlighted the limitations of in
      vitro systems in modeling whole organism responses, and additionally identified
      potential predictive biomarkers of toxicity.

PMID- 16611357
TI  - Degenerative suspensory ligament desmitis as a systemic disorder characterized by
      proteoglycan accumulation.
AB  - BACKGROUND: Degenerative suspensory ligament desmitis (DSLD) is a debilitating
      disorder thought to be limited to suspensory ligaments of Peruvian Pasos,
      Peruvian Paso crosses, Arabians, American Saddlebreds, American Quarter Horses,
      Thoroughbreds, and some European breeds. It frequently leads to persistent,
      incurable lameness and need to euthanize affected horses. The pathogenesis
      remains unclear, though the disease appears to run in families. Treatment and
      prevention are empirical and supportive, and not effective in halting the
      progression of the disease. Presently, the presumptive diagnosis of DSLD is
      obtained from patient signalment and history, clinical examination, and
      ultrasonographic examination of clinically affected horses, and is confirmed at
      post mortem examination. Presently, there are no reliable methods of diagnosing
      DSLD in asymptomatic horses. The goal of this study was to characterize and
      define the disorder in terms of tissue involvement at the macroscopic and
      microscopic levels. RESULTS: We examined tissues and organs from 28 affected
      horses (22 Peruvian Pasos, 6 horses of other breeds) and from 8 control horses.
      Histopathological examination revealed the presence of excessive amounts of
      proteoglycans in the following tissues removed from DSLD-affected horses:
      suspensory ligaments, superficial and deep digital flexor tendons, patellar and
      nuchal ligaments, cardiovascular system, and sclerae. Electron microscopy
      demonstrated changes in diameters of collagen fibrils in the tendon, and in
      smooth muscle cells of the media of the aorta compatible with increased cell
      permeability in DSLD-affected cells. Separation of tendon extracts by gel
      chromatography revealed the presence of additional proteoglycan(s) in extracts
      from affected, but not control extracts. CONCLUSION: This study demonstrates for
      the first time that DSLD, a disease process previously thought to be limited to
      the suspensory ligaments of the distal limbs of affected horses, is in fact a
      systemic disorder involving tissues and organs with significant connective tissue
      component. Abnormal accumulation of proteoglycans between collagen and elastic
      fibers rather than specific collagen fibril abnormalities is the most prominent
      histological feature of DSLD. Because of this observation and because of the
      involvement of many other tendons and ligaments beside the suspensory ligament,
      and of non-ligamentous tissue we, therefore, propose that equine systemic
      proteoglycan accumulation or ESPA rather than DSLD is a more appropriate name for
      this condition.

PMID- 16611358
TI  - IL-10, IL-6 and CD14 polymorphisms and sepsis outcome in ventilated very low
      birth weight infants.
AB  - BACKGROUND: Genetic variation in the innate immune system of the host may play a
      role in determining the risk of developing infection, as well as outcome from
      infection. METHODS: Infectious complications were retrospectively determined in
      293 (233 African-American (AA), 57 Caucasian and 3 Hispanic) mechanically
      ventilated very low birth weight (VLBW) infants (<1500 grams at birth) who were
      genotyped for the IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T single
      nucleotide polymorphisms (SNPs). RESULTS: The IL-6 -174C allele was associated
      with an increased incidence of late blood stream infection (BSI) in AA but not
      Caucasian infants. In AA infants with the C allele the incidence of late BSI was
      20/29 (69%) compared to 94/204 (46%) in homozygous GG infants (RR 2.6, 95% CI:
      1.1-6.0, p = 0.021). The IL-10 -1082A allele was associated with an increased
      incidence of late BSI. One or more episodes of late BSI developed in 14 (35%) of
      40 infants with the GG genotype, 71 (49%) of 145 infants with the GA genotype and
      63 (58%) of 108 infants with the AA genotype (p = 0.036). Infants with the A
      allele (AA or GA genotypes) had an incidence of late BSI that was 134/253 (53%)
      compared to 14/40 (35%) in homozygous GG infants (RR 2.1, 95% CI: 1.04-4.19, p =
      0.035). The CD14 -260 C/T SNP did not alter the overall risk for BSI in
      ventilated VLBW infants. Multiple BSI episodes were more common in the TT
      genotype group (CC: 17%, CT: 11%, TT: 30%, p = 0.022). This effect was due to the
      strong effect of the TT genotype on the incidence of multiple BSI in AA infants
      (CC: 15%, CT: 11%, TT: 39%, p = 0.003). CONCLUSION: The IL-6 -174 G/C, IL-10 
      1082 G/A and CD14 -260 C/T SNPs may alter risk for BSI in ventilated VLBW
      infants.

PMID- 16611359
TI  - Dissecting trait heterogeneity: a comparison of three clustering methods applied
      to genotypic data.
AB  - BACKGROUND: Trait heterogeneity, which exists when a trait has been defined with
      insufficient specificity such that it is actually two or more distinct traits,
      has been implicated as a confounding factor in traditional statistical genetics
      of complex human disease. In the absence of detailed phenotypic data collected
      consistently in combination with genetic data, unsupervised computational
      methodologies offer the potential for discovering underlying trait heterogeneity.
      The performance of three such methods--Bayesian Classification, Hypergraph-Based
      Clustering, and Fuzzy k-Modes Clustering--appropriate for categorical data were
      compared. Also tested was the ability of these methods to detect trait
      heterogeneity in the presence of locus heterogeneity and/or gene-gene
      interaction, which are two other complicating factors in discovering genetic
      models of complex human disease. To determine the efficacy of applying the
      Bayesian Classification method to real data, the reliability of its internal
      clustering metrics at finding good clusterings was evaluated using permutation
      testing. RESULTS: Bayesian Classification outperformed the other two methods,
      with the exception that the Fuzzy k-Modes Clustering performed best on the most
      complex genetic model. Bayesian Classification achieved excellent recovery for
      75% of the datasets simulated under the simplest genetic model, while it achieved
      moderate recovery for 56% of datasets with a sample size of 500 or more (across
      all simulated models) and for 86% of datasets with 10 or fewer nonfunctional loci
      (across all simulated models). Neither Hypergraph Clustering nor Fuzzy k-Modes
      Clustering achieved good or excellent cluster recovery for a majority of datasets
      even under a restricted set of conditions. When using the average log of class
      strength as the internal clustering metric, the false positive rate was
      controlled very well, at three percent or less for all three significance levels
      (0.01, 0.05, 0.10), and the false negative rate was acceptably low (18 percent)
      for the least stringent significance level of 0.10. CONCLUSION: Bayesian
      Classification shows promise as an unsupervised computational method for
      dissecting trait heterogeneity in genotypic data. Its control of false positive
      and false negative rates lends confidence to the validity of its results. Further
      investigation of how different parameter settings may improve the performance of
      Bayesian Classification, especially under more complex genetic models, is
      ongoing.

PMID- 16611360
TI  - Human rights, health and the state in Bangladesh.
AB  - BACKGROUND: This paper broadly discusses the role of the State of Bangladesh in
      the context of the health system and human rights. The interrelation between
      human rights, health and development are well documented. The recognition of
      health as a fundamental right by WHO and subsequent approval of health as an
      instrument of welfare by the Universal Declaration of Human Rights (UDHR) and the
      International Covenant on Social, Economic and Cultural Rights (ICSECR) further
      enhances the idea. Moreover, human rights are also recognized as an expedient of
      human development. The state is entrusted to realize the rights enunciated in the
      ICSECR. DISCUSSION: In exploring the relationship of the human rights and health
      situation in Bangladesh, it is argued, in this paper, that the constitution and
      major policy documents of the Bangladesh government have recognized the health
      rights and development. Bangladesh has ratified most of the international
      treaties and covenants including ICCPR, ICESCR; and a signatory of international
      declarations including Alma-Ata, ICPD, Beijing declarations, and Millennium
      Development Goals. However the implementation of government policies and plans in
      the development of health institutions, human resources, accessibility and
      availability, resource distribution, rural-urban disparity, the male-female gap
      has put the health system in a dismal state. Neither the right to health nor the
      right to development has been established in the development of health system or
      in providing health care. SUMMARY: The development and service pattern of the
      health system have negative correlation with human rights and contributed to the
      underdevelopment of Bangladesh. The government should take comprehensive approach
      in prioritizing the health rights of the citizens and progressive realization of
      these rights.

PMID- 16611361
TI  - Generation of mice harbouring a conditional loss-of-function allele of Gata6.
AB  - The zinc finger transcription factor GATA6 is believed to have important roles in
      the development of several organs including the liver, gastrointestinal tract and
      heart. However, analyses of the contribution of GATA6 toward organogenesis have
      been hampered because Gata6-/- mice fail to develop beyond gastrulation due to
      defects in extraembryonic endoderm function. We have therefore generated a mouse
      line harbouring a conditional loss-of-function allele of Gata6 using Cre/loxP
      technology. LoxP elements were introduced into introns flanking exon 2 of the
      Gata6 gene by homologous recombination in ES cells. Mice containing this altered
      allele were bred to homozygosity and were found to be viable and fertile. To
      assess the functional integrity of the loxP sites and to confirm that we had
      generated a Gata6 loss-of-function allele, we bred Gata6 'floxed' mice to EIIa
      Cre mice in which Cre is ubiquitously expressed, and to Villin-Cre mice that
      express Cre in the epithelial cells of the intestine. We conclude that we have
      generated a line of mice in which GATA6 activity can be ablated in a cell type
      specific manner by expression of Cre recombinase. This line of mice can be used
      to establish the role of GATA6 in regulating embryonic development and various
      aspects of mammalian physiology.

PMID- 16611362
TI  - Piezoelectric osteotomy in hand surgery: first experiences with a new technique.
AB  - BACKGROUND: In hand and spinal surgery nerve lesions are feared complications
      with the use of standard oscillating saws. Oral surgeons have started using a
      newly developed ultrasound bone scalpel when performing precise osteotomies. By
      using a frequency of 25-29 kHz only mineralized tissue is cut, sparing the soft
      tissue. This reduces the risk of nerve lesions. As there is a lack of experience
      with this technique in the field of orthopaedic bone surgery, we performed the
      first ultrasound osteotomy in hand surgery. METHOD: While performing a
      correctional osteotomy of the 5th metacarpal bone we used the Piezosurgery Device
      from Mectron [Italy] instead of the usual oscillating saw. We will report on our
      experience with one case, with a follow up time of one year. RESULTS: The cut was
      highly precise and there were no vibrations of the bone. The time needed for the
      operation was slightly longer than the time needed while using the usual saw.
      Bone healing was good and at no point were there any neurovascular disturbances.
      CONCLUSION: The Piezosurgery Device is useful for small long bone osteotomies.
      Using the fine tip enables curved cutting and provides an opportunity for new
      osteotomy techniques. As the device selectively cuts bone we feel that this
      device has great potential in the field of hand- and spinal surgery.

PMID- 16611363
TI  - Regulation of the ovarian follicular vasculature.
AB  - Angiogenesis is associated with follicular development and is regulated
      independently within each follicle potentially making the functioning of its
      vasculature critically important in determining its fate. This review examines
      the various ways in which follicular angiogenesis may be monitored, describes the
      follicular localisation and changes in pro- and anti-angiogenic factors that may
      regulate the process and how antagonists may be used to elucidate their
      physiological role in vivo. Thus, inhibition of vascular endothelial growth
      factor (VEGF), VEGF receptor-2, vascular endothelial cell cadherin or
      interference with the angiopoietin system can inhibit follicular development or
      prevent ovulation.

PMID- 16611365
TI  - Regulation of ovulation rate in mammals: contribution of sheep genetic models.
AB  - Ovarian folliculogenesis in mammals from the constitution of primordial follicles
      up to ovulation is a reasonably well understood mechanism. Nevertheless,
      underlying mechanisms that determine the number of ovulating follicles were
      enigmatic until the identification of the fecundity genes affecting ovulation
      rate in sheep, bone morphogenetic protein-15 (BMP-15), growth and differentiation
      factor-9 (GDF-9) and BMP receptor-1B (BMPR-1B). In this review, we focus on the
      use of these sheep genetic models for understanding the role of the BMP system as
      an intra-ovarian regulator of follicular growth and maturation, and finally,
      ovulation rate.

PMID- 16611364
TI  - Oocyte-granulosa cell interactions during mouse follicular development:
      regulation of kit ligand expression and its role in oocyte growth.
AB  - Ovarian folliculogenesis is regulated by both endocrine and intraovarian
      mechanisms that coordinate the processes of oocyte growth and somatic cell
      proliferation and differentiation. Within the follicle, paracrine interactions
      between the oocyte and surrounding granulosa cells are critical for normal cell
      development and function. This review focuses on the role of paracrine
      interactions during early oocyte and follicular development that ensure proper
      coordination of oocyte and somatic cell function. Particular emphasis is given to
      granulosa cell-derived Kit Ligand (KitL), whose functional importance for oocyte
      growth has been demonstrated by a wide range of in vivo and in vitro studies.
      Reported interactions between KitL and oocyte-derived growth differentiation
      factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) suggest the molecular
      basis of oocyte-granulosa cell interactions, but also hint at the complexity of
      these communications. These paracrine interactions and the structure of the
      oocyte-granulosa cell interface are follicle stage-specific and regulated by FSH.
      Elucidation of the molecular mechanisms that promote the development of healthy
      oocytes with good developmental competence has potential applications for
      improving fertility and for in vitro growth systems for oocytes from domestic
      animals and humans.

PMID- 16611366
TI  - Smad signalling in the ovary.
AB  - It has now been a decade since the first discovery of the intracellular Smad
      proteins, the downstream signalling molecules of one of the most important growth
      factor families in the animal kingdom, the transforming growth factor beta (TGF
      beta) superfamily. In the ovary, several TGF-beta superfamily members are
      expressed by the oocyte, granulosa and thecal cells at different stages of
      folliculogenesis, and they signal mainly through two different Smad pathways in
      an autocrine/paracrine manner. Defects in the upstream signalling cascade
      molecules, the ligands and receptors, are known to have adverse effects on
      ovarian organogenesis and folliculogenesis, but the role of the individual Smad
      proteins in the proper function of the ovary is just beginning to be understood
      for example through the use of Smad knockout models. Although most of the
      different Smad knockouts are embryonic lethal, it is known, however, that in
      Smad1 and Smad5 knockout mice primordial germ cell development is impaired and
      that Smad3 deficient mice harbouring a deletion in exon 8 exhibit impaired
      folliculogenesis and reduced fertility. In this minireview we discuss the role of
      Smad structure and function in the ovarian context.

PMID- 16611368
TI  - Evaluation of a decision aid for prenatal testing of fetal abnormalities: a
      cluster randomised trial [ISRCTN22532458].
AB  - BACKGROUND: By providing information on the relative merits and potential harms
      of the options available and a framework to clarify preferences, decision aids
      can improve knowledge and realistic expectations and decrease decisional conflict
      in individuals facing decisions between alternative forms of action. Decision
      making about prenatal testing for fetal abnormalities is often confusing and
      difficult for women and the effectiveness of decision aids in this field has not
      been established. This study aims to test whether a decision aid for prenatal
      testing of fetal abnormalities, when compared to a pamphlet, improves women's
      informed decision-making and decreases decisional conflict. METHODS/DESIGN: A
      cluster designed randomised controlled trial is being conducted in Victoria,
      Australia. Fifty General Practitioners (GPs) have been randomised to one of two
      arms: providing women with either a decision aid or a pamphlet. The two primary
      outcomes will be measured by comparing the difference in percentages of women
      identified as making an informed choice and the difference in mean decisional
      conflict scores between the two groups. Data will be collected from women using
      questionnaires at 14 weeks and 24 weeks gestation. The sample size of 159 women
      in both arms of the trial has been calculated to detect a difference of 18% (50
      to 68%) in informed choice between the two groups. The required numbers have been
      adjusted to accommodate the cluster design, miscarriage and participant lost--to-
      follow up. Baseline characteristics of women will be summarised for both arms of
      the trial. Similarly, characteristics of GPs will be compared between arms.
      Differences in the primary outcomes will be analysed using 'intention-to-treat'
      principles. Appropriate regression techniques will adjust for the effects of
      clustering and include covariates to adjust for the stratifying variable and
      major potential confounding factors. DISCUSSION: The findings from this trial
      will make a significant contribution to improving women's experience of prenatal
      testing and will have application to a variety of maternity care settings. The
      evaluation of a tailored decision aid will also have implications for pregnancy
      care providers by identifying whether or not such a resource will support their
      role in providing prenatal testing information.

PMID- 16611369
TI  - Wildlife reintroduction: considerations of habitat quality at the release site.
AB  - BACKGROUND: Assessing the suitability of a habitat prior to the release of
      animals is vital. Proper assessment of the flora will allow reintroduction
      programmes to determine whether the area will be capable of supporting the
      released animals in the long-term. Here data are presented from an island in
      Central Kalimantan, Indonesia which has been used as a release site for agile
      gibbons (Hylobates agilis albibarbis) since January 2003. RESULTS: Methods and
      results regarding fruit abundance, fruit productivity, tree density and diversity
      are presented. This information is then analysed in the context of the island's
      suitability to sustain released gibbons and without impact on the resident fauna.
      Based on the above ecological characteristics, the final carrying capacity of the
      island is estimated to be between 3 and 19 gibbons. CONCLUSION: These data
      highlight the need to survey areas being considered for release of gibbon prior
      to the release taking place. For reintroductions to be successful, long-term
      habitat assessment is vital, both pre- and post-release.

PMID- 16611367
TI  - Evidence of a local negative role for cocaine and amphetamine regulated
      transcript (CART), inhibins and low molecular weight insulin like growth factor
      binding proteins in regulation of granulosa cell estradiol production during
      follicular waves in cattle.
AB  - The ability of ovarian follicles to produce large amounts of estradiol is a
      hallmark of follicle health status. Estradiol producing capacity is lost in
      ovarian follicles before morphological signs of atresia. A prominent wave like
      pattern of growth of antral follicles is characteristic of monotocous species
      such as cattle, horses and humans. While our knowledge of the role of pituitary
      gonadotropins in support of antral follicle growth and development is well
      established, the intrinsic factors that suppress estradiol production and may
      help promote atresia during follicular waves are not well understood. Numerous
      growth factors and cytokines have been reported to suppress granulosa cell
      estradiol production in vitro, but the association of expression of many such
      factors in vivo with follicle health status and their physiological significance
      are not clear. The purpose of this review is to discuss the in vivo and in vitro
      evidence supporting a local physiological role for cocaine and amphetamine
      regulated transcript, inhibins and low molecular weight insulin like growth
      factor binding proteins in negative regulation of granulosa cell estradiol
      production, with emphasis on evidence from the bovine model system.

PMID- 16611370
TI  - Diagnostic value of real-time polymerase chain reaction to detect viruses in
      young children admitted to the paediatric intensive care unit with lower
      respiratory tract infection.
AB  - INTRODUCTION: The aetiology of lower respiratory tract infections in young
      children admitted to the paediatric intensive care unit (PICU) is often difficult
      to establish. However, most infections are believed to be caused by respiratory
      viruses. A diagnostic study was performed to compare conventional viral tests
      with the recently developed real-time PCR technique. METHOD: Samples from
      children aged under 5 years presenting to a tertiary PICU suspected of having a
      lower respiratory tract infection were tested using conventional methods (viral
      culture and immunofluorescence) and real-time PCR during the winter season from
      December 2004 to May 2005. Conventional methods were used to check for
      respiratory syncytial virus, influenzavirus, parainfluenzavirus 1-3, rhinoviruses
      and adenoviruses. Real-time PCR was used to test for respiratory syncytial virus,
      influenzavirus, parainfluenzavirus 1-4, rhinoviruses, adenoviruses, human
      coronaviruses OC43, NL63 and 229E, human metapneumovirus, Mycoplasma pneumoniae
      and Chlamydia pneumoniae. RESULTS: A total of 23 patients were included, of whom
      11 (48%) were positive for a respiratory virus by conventional methods. Real-time
      PCR confirmed all of these positive results. In addition, real-time PCR
      identified 22 more viruses in 11 patients, yielding a total of 22 (96%) patients
      with a positive sample. More than one virus was detected in eight (35%) children.
      CONCLUSION: Real-time PCR for respiratory viruses was found to be a sensitive and
      reliable method in PICU patients with lower respiratory tract infection,
      increasing the diagnostic yield twofold compared to conventional methods.

PMID- 16611371
TI  - Effect of a farnesyl transferase inhibitor (R115777) on ductal carcinoma in situ
      of the breast in a human xenograft model and on breast and ovarian cancer cell
      growth in vitro and in vivo.
AB  - INTRODUCTION: The ras pathway is essential for cell growth and proliferation. The
      effects of R115777, a farnesyl transferase inhibitor, were investigated in cancer
      cell lines expressing varying levels of growth factor receptors and with
      differing ras status. Effects on tumour xenografts and human ductal carcinoma in
      situ (DCIS) of the breast in a xenograft mouse model were also tested. METHOD: In
      vitro, the concentrations required to reduce cell numbers by 50% (50% inhibitory
      concentration) were established (MDA-MB231, MCF-7, MCF-7/HER2-18, BT-474, SK-BR3
      and SKOV3). Human DCIS was implanted in nude mice or, in separate experiments,
      cultured cells were injected (MDA-MB231, MCF-7/HER2-18, SKOV3) and allowed to
      form tumours. Proliferation and apoptosis were determined by immunohistochemistry
      in xenografts and cell tumours. RESULTS: The 50% inhibitory concentrations varied
      a hundred-fold, from 39 nmol/l (+/- 26 nmol/l) for SKBR3 to 5.9 micromol/l(+/-
      0.8 micromol/l) for MDA-MB231. In MCF-7/HER2-18 and SKOV3 cells the levels of
      tumour growth inhibition were approximately 85% and 40%, respectively. There was
      a significant decrease in the cell turnover index (CTI; proliferation/apoptosis).
      In MDA-MB 231 with activated k-ras no inhibition was observed. In treated DCIS
      xenografts proliferation decreased and apoptosis increased. The CTI ratio between
      the start and 1 and 2 weeks of treatment were 1.99 and 1.50, respectively, for
      controls and 0.85 (P = 0.005) and 0.75 (P = 0.08) for treated xenografts.
      CONCLUSION: Treatment with the farnesyl transferase inhibitor reduced cell growth
      in vitro and cell tumour growth in vivo. In DCIS treatment resulted in a reduced
      CTI. R115777 is a promising treatment for breast cancer but the relation between
      effect and growth factor receptor and ras status has to be established.

PMID- 16611372
TI  - Identification and characterization of the carboxy-terminal region of Sip-1, a
      novel autoantigen in Behcet's disease.
AB  - Given the lack of a serological test specific for Behcet's disease, its diagnosis
      rests upon clinical criteria. The clinical diagnosis is nevertheless difficult
      because the disease manifestations vary widely, especially at the onset of
      disease. The aim of this study was to identify molecules specifically recognized
      by serum autoantibodies in patients with Behcet's disease and to evaluate their
      diagnostic value. We screened a cDNA library from human microvascular endothelial
      cells with serum IgG from two patients with Behcet's disease and isolated a
      reactive clone specific to the carboxy-terminal subunit of Sip1 (Sip1 C-ter).
      Using ELISA, we measured IgG, IgM and IgA specific to Sip1 C-ter in patients with
      various autoimmune diseases characterized by the presence of serum anti
      endothelial cell antibodies, such as Behcet's disease, systemic lupus
      erythematosus, systemic sclerosis and various forms of primary vasculitis, as
      well as in patients with diseases that share clinical features with Behcet's
      disease, such as inflammatory bowel disease and uveitis. IgM immunoreactivity to
      Sip1 C-ter was significantly higher in patients with Behcet's disease and in
      patients with primary vasculitis than in the other groups of patients and healthy
      subjects tested (P < 10-4 by Mann-Whitney test). ELISA detected IgG specific to
      Sip1 C-ter in sera from 11/56 (20%) patients with Behcet's disease, IgM in 23/56
      (41%) and IgA in 9/54 (17%). No sera from patients with systemic lupus
      erythematosus, systemic sclerosis, inflammatory bowel disease, uveitis or healthy
      subjects but 45% of sera from patients with primary vasculitis contained IgM
      specific to Sip1 C-ter. Serum levels of soluble E-selectin, a marker of
      endothelial activation and inflammation, correlated with levels of serum IgM anti
      Sip-1 C-ter in patients with Behcet's disease (r = 0.36, P = 0.023). In
      conclusion, Sip1 C-ter is a novel autoantigen in Behcet's disease. IgM specific
      to Sip1 C-ter might be useful in clinical practice as an immunological marker of
      endothelial dysfunction in vasculitis.

PMID- 16611373
TI  - Suppression of adaptive immunity to heterologous antigens during Plasmodium
      infection through hemozoin-induced failure of dendritic cell function.
AB  - BACKGROUND: Dendritic cells (DCs) are central to the initiation and regulation of
      the adaptive immune response during infection. Modulation of DC function may
      therefore allow evasion of the immune system by pathogens. Significant depression
      of the host's systemic immune response to both concurrent infections and
      heterologous vaccines has been observed during malaria infection, but the
      mechanisms underlying this immune hyporesponsiveness are controversial. RESULTS:
      Here, we demonstrate that the blood stages of malaria infection induce a failure
      of DC function in vitro and in vivo, causing suboptimal activation of T cells
      involved in heterologous immune responses. This effect on T-cell activation can
      be transferred to uninfected recipients by DCs isolated from infected mice.
      Significantly, T cells activated by these DCs subsequently lack effector
      function, as demonstrated by a failure to migrate to lymphoid-organ follicles,
      resulting in an absence of B-cell responses to heterologous antigens.
      Fractionation studies show that hemozoin, rather than infected erythrocyte (red
      blood cell) membranes, reproduces the effect of intact infected red blood cells
      on DCs. Furthermore, hemozoin-containing DCs could be identified in T-cell areas
      of the spleen in vivo. CONCLUSION: Plasmodium infection inhibits the induction of
      adaptive immunity to heterologous antigens by modulating DC function, providing a
      potential explanation for epidemiological studies linking endemic malaria with
      secondary infections and reduced vaccine efficacy.

PMID- 16611374
TI  - Influence of specific nutrients on progression of atherosclerosis, vascular
      function, haemostasis and inflammation in coronary heart disease patients: a
      systematic review.
AB  - Epidemiological evidence suggests that the diet influences CHD risk, although the
      protective effects of dietary intervention for patients in diseased states has
      gained less attention. Secondary care prevention strategies for patients often
      involves drug therapy that is expensive and can result in undesirable side
      effects. Therefore, it is potentially beneficial to utilise other strategies,
      such as diet, in the management of CHD. A systematic review was conducted to
      examine the effects of specific nutrients on progression of atherosclerosis,
      vascular function, haemostasis and inflammation in CHD patients. Results show
      substantial evidence for the efficacy of n-3 oils in reducing cardiovascular
      mortality and one mechanism may be related to the stabilisation of vulnerable
      atherosclerotic plaques, although the effects on progression of atherosclerosis,
      haemostatic activity and vascular inflammation remain equivocal. Promising data
      also exist for the efficacy of flavonoid-rich foods for improving endothelial
      function, although strong clinical endpoint evidence is lacking. The variation in
      the efficacy of certain nutrients in CHD patients may be explained by genetics,
      existing risk factors, psychosocial factors and methodological issues, although
      these are often not adequately taken into consideration. We conclude that there
      is a need to undertake more appropriately designed trials in specific clinical
      populations, controlling for additional lifestyle and risk factors, examining
      potential interactions with medications, and also establishing methods to
      increase compliance to dietary recommendations before specific nutrients can be
      widely prescribed for secondary prevention. Future research should also utilise
      techniques that provide a direct measure of atherosclerosis.

PMID- 16611375
TI  - Methodological approaches to study dietary patterns in relation to risk of
      coronary heart disease and stroke.
AB  - Dietary pattern analysis, which reflects the complexity of dietary intake, has
      received considerable attention by nutritional epidemiology. For a long time, two
      general approaches have been used to define these summary variables in
      observational studies. The exploratory approach is based only on the data of the
      study, whereas the hypothesis-oriented approach constructs pattern variables
      based on scientific evidence available before the study. Recently, a new
      statistical method, reduced rank regression, was applied to nutritional
      epidemiology that is exploratory by nature, but can use scientific evidence by
      focusing on disease-related dietary components or biomarkers. Several studies,
      both observational and clinical, suggest that dietary patterns may predict the
      risk of CHD and stroke. In the present review, we describe the results of these
      studies and the available evidence regarding the relationships between dietary
      patterns and risk of CVD and we discuss limitations and strengths of the
      statistical methods used to extract dietary patterns.

PMID- 16611376
TI  - In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95)
      independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human
      peripheral blood lymphocytes.
AB  - In vitro folate deficiency is associated with S phase accumulation and apoptosis
      in various cell types. To investigate the role of p53 and two apoptosis-related
      molecules, bcl-2 and Fas antigen (Apo-1, CD95), in the mechanism whereby folate
      deficient lymphocytes accumulate and undergo apoptosis in the S phase, normal
      human peripheral blood lymphocytes were cultured for 3-9 d in control medium or
      in specially ordered and formulated HAM's F-10 medium lacking folic acid,
      thymidine and hypoxanthine. Cells were stimulated with phytohaemagglutinin for
      the final 72 h prior to harvesting. The results indicate that p53 expression was
      downregulated in folate-deficient lymphocytes when compared with the control
      lymphocytes during the relevant period of S phase accumulation and apoptosis. In
      addition, folate deficiency was also found to downregulate IL-2, Fas antigen and
      bcl-2 expression, in terms of either mRNA or protein levels. The downregulation
      of Fas antigen suggests that folate deficiency-induced apoptosis probably does
      not occur via the Fas pathway. As IL-2 is a known inducer of bcl-2, and the
      downregulation of bcl-2 induces apoptosis, the downregulation of IL-2 and bcl-2
      is suggested to play an important role in apoptosis. The complete rescue of
      folate-deficient lymphocytes from apoptosis was achieved by folic acid, thymidine
      or hypoxanthine alone or thymidine and hypoxanthine in combination. These results
      suggest that IL-2 depletion by folate deficiency in lymphocytes reduces the bcl-2
      level, thereby triggering deoxynucleoside triphosphate pool imbalance and p53
      independent apoptosis.

PMID- 16611377
TI  - Effect of dietary methionine on plasma and liver cholesterol concentrations in
      rats and expression of hepatic genes involved in cholesterol metabolism.
AB  - Methionine has been shown to increase plasma cholesterol in animals. In the
      present study, mechanisms were investigated by which methionine could alter
      cholesterol metabolism. In the first experiment, forty growing rats were fed four
      casein-based diets differing in methionine content (2.6, 3.5, 4.5 or 6.0 g/kg)
      for 14 d. In the second experiment, isolated rat hepatocytes were incubated in
      media supplemented with 50, 100 or 200 micromol/l methionine. Dietary methionine
      tended to increase plasma homocysteine concentrations in the rats (P=0.058). A
      weak positive correlation between circulating homocysteine and plasma cholesterol
      was observed (R2 0.27, P<0.01). Rats fed 3.5 g/kg or more of methionine had
      higher concentrations of cholesterol in their plasma, in lipoprotein fractions of
      density (rho; kg/l) 1.006<rho<1.063 and rho>1.063, and in liver than rats fed 2.6
      g/kg methionine. Rats fed 6 g/kg methionine had a higher hepatic expression of 3
      hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol-7alpha-hydroxylase
      than rats fed less methionine. The phosphatidylcholine:phosphatidylethanolamine
      ratio in rat liver increased with rising dietary methionine concentration; the
      relative mRNA concentrations of phosphatidylethanolamine N-methyltransferase and
      cystathionine beta-synthase remained unaffected. Hepatocytes incubated in media
      supplemented with 100 or 200 micromol/l methionine had a higher cholesterol
      synthesis than hepatocytes incubated in a medium supplemented with 50 micromol/l
      methionine; the LDL uptake in hepatocytes was independent of the methionine
      concentration of the medium. In conclusion, the present study suggests that
      dietary methionine induces hypercholesterolaemia at least in part via an enhanced
      hepatic cholesterol synthesis.

PMID- 16611378
TI  - Uptake of triacylglycerol-rich lipoproteins of differing triacylglycerol
      molecular species and unsaponifiable content by liver cells.
AB  - The fatty acid composition of dietary oils can modulate the incorporation of
      triacylglycerol-rich lipoproteins (TRL) into hepatocytes, thus affecting the
      atherogenicity of these particles. However, nothing is known about the effect of
      the unsaponifiable fraction of the oils. In the present study, we evaluated the
      influence of these components on the uptake of TRL by rat primary hepatocytes.
      TRL were isolated from human serum after the intake of meals enriched in high
      oleic sunflower oil (HOSO), virgin olive oil (VOO) or VOO enriched in its own
      unsaponifiable fraction (EVO). HOSO and HOSO-TRL differed from VOO and EVO and
      their corresponding TRL in the composition of triacylglycerol molecular species
      and of the unsaponifiable fraction. Furthermore, the increase in the
      unsaponifiable fraction of VOO led to changes in the triacylglycerol molecular
      species in the EVO-TRL. On incubation with hepatocytes, HOSO-TRL were taken up at
      a faster rate than VOO-TRL or EVO-TRL. In addition, in comparison to VOO-TRL,
      HOSO-TRL increased the expression of mRNA for the LDL receptor-related protein
      receptor, which plays an important role in the internalisation of remnant
      lipoproteins. EVO-TRL also increased LDL receptor-related protein mRNA expression
      in comparison with VOO-TRL, but this change was not accompanied by a rise in the
      uptake rate, suggesting that the unsaponifiable fraction of VOO may inhibit LDL
      receptor-related protein expression or activity post-transcriptionally. In
      conclusion, TRL from dietary oils with differing triacylglycerol molecular
      species and unsaponifiable fraction content are taken up by liver cells at
      different rates, and this may be important in the atherogenicity of these
      particles.

PMID- 16611379
TI  - Absorption and metabolism of red orange juice anthocyanins in rats.
AB  - Anthocyanins are natural pigments that could be involved in various health
      effects. Red oranges are an important dietary source of anthocyanins, including
      cyanidin 3-glucoside (Cy 3-glc) and an acylated derivative, cyanidin 3-(6''
      malonyl)-glucoside (Cy 3-malglc). The aim of this study was to evaluate the
      absorption and metabolism of red orange anthocyanins in rats fed an anthocyanin
      enriched diet for 12 d (approximately 2.8 micromol anthocyanins/d). Furthermore,
      the absorption of these anthocyanins was studied in both the stomach and
      intestine using in situ models in rats. Anthocyanin metabolites were identified
      and quantified by HPLC-electrospray ionization tandem MS and HPLC-diode array
      detection, respectively. The red orange anthocyanins, Cy 3-glc and Cy 3-malglc,
      as well as their respective methylated derivatives, were recovered in urine after
      red orange juice intake. The 24 h urinary excretion of total anthocyanins was low
      (0.081 (SEM 0.009) % of the ingested amount). However, a high proportion (about
      20 %) of red orange anthocyanins was absorbed from the stomach. More Cy 3-malglc
      than Cy 3-glc was absorbed in the intestine. This study thus indicated that red
      orange juice anthocyanins were rapidly absorbed from both stomach and small
      intestine, and then excreted in the urine as intact and methylated forms.
      Moreover, the absorption and metabolism of acylated anthocyanins and non-acylated
      anthocyanins were similar.

PMID- 16611380
TI  - Biochemical hepatic alterations and body lipid composition in the herbivorous
      grass carp (Ctenopharyngodon idella) fed high-fat diets.
AB  - High-fat diets may have favourable effects on growth of some carnivorous fish
      because of the protein-sparing effect of lipids, but high-fat diets also exert
      some negative impacts on flesh quality. The goal of the study was therefore to
      determine the effects of fat-enriched diets in juvenile grass carp
      (Ctenopharyngodon idella) as a typical herbivorous fish on growth and possible
      lipid metabolism alterations. Three isonitrogenous diets containing 2, 6 or 10 %
      of a mixture of lard, maize oil and fish oil (1:1:1, by weight) were applied to
      fish for 8 weeks in a recirculation system. Data show that feeding diets with
      increasing lipid levels resulted in lowered feed intake, decreased growth and
      feed efficiency, and increased mesenteric fat tissue weight. Concomitantly,
      alteration of lipoprotein synthesis and greater level of lipid peroxidation were
      apparent in blood. In liver, muscle and mesenteric fat tissue, the percentages of
      alpha-linolenic acid and DHA were significantly increased or tended to increase
      with higher dietary lipid levels. Biochemical activity measurements performed on
      liver showed that, with the increase in dietary lipid level, there was a decrease
      in both mitochondrial and peroxisomal fatty acid oxidation capacities, which
      might contribute, at least in part, to the specific accumulation of alpha
      linolenic acid and DHA into cells more active in membrane building. On the whole,
      grass carp have difficulty in energetically utilising excess dietary fat,
      especially when enriched in n-3 PUFA that are susceptible to peroxidation.

PMID- 16611381
TI  - Dietary acetic acid reduces serum cholesterol and triacylglycerols in rats fed a
      cholesterol-rich diet.
AB  - To investigate the efficacy of the intake of vinegar for prevention of
      hyperlipidaemia, we examined the effect of dietary acetic acid, the main
      component of vinegar, on serum lipid values in rats fed a diet containing 1 %
      (w/w) cholesterol. Animals were allowed free access to a diet containing no
      cholesterol, a diet containing 1 % cholesterol without acetic acid, or a diet
      containing 1 % cholesterol with 0.3 % (w/w) acetic acid for 19 d. Then, they were
      killed after food deprivation for 7 h. Cholesterol feeding increased serum total
      cholesterol and triacylglycerol levels. Compared with the cholesterol-fed group,
      the cholesterol and acetic acid-fed group had significantly lower values for
      serum total cholesterol and triacylglycerols, liver ATP citrate lyase (ATP-CL)
      activity, and liver 3-hydroxy-3-methylglutaryl-CoA content as well as liver mRNA
      levels of sterol regulatory element binding protein-1, ATP-CL and fatty acid
      synthase (P<0.05). Further, the serum secretin level, liver acyl-CoA oxidase
      expression, and faecal bile acid content were significantly higher in the
      cholesterol and acetic acid-fed group than in the cholesterol-fed group (P<0.05).
      However, acetic acid feeding affected neither the mRNA level nor activity of
      cholesterol 7alpha-hydroxylase. In conclusion, dietary acetic acid reduced serum
      total cholesterol and triacylglycerol: first due to the inhibition of lipogenesis
      in liver; second due to the increment in faecal bile acid excretion in rats fed a
      diet containing cholesterol.

PMID- 16611382
TI  - Effect of potato on acid-base and mineral homeostasis in rats fed a high-sodium
      chloride diet.
AB  - Excessive dietary NaCl in association with a paucity of plant foods, major
      sources of K alkaline salts, is a common feature in Western eating habits which
      may lead to acid-base disorders and to Ca and Mg wasting. In this context, to
      evaluate the effects of potato, rich in potassium citrate, on acid-base
      homeostasis and mineral retention, Wistar rats were fed wheat starch (WS) or
      cooked potato (CP) diets with a low (0.5 %) or a high (2 %) NaCl content during 3
      weeks. The replacement of WS by CP in the diets resulted in a significant urinary
      alkalinisation (pH from 5.5 to 7.3) parallel to a rise in citrate and K
      excretion. Urinary Ca and Mg elimination represented respectively 17 and 62 % of
      the daily absorbed mineral in rats fed the high-salt WS diet compared with 5 and
      28 % in rats fed the high-salt CP diet. The total SCFA concentration in the
      caecum was 3-fold higher in rats fed the CP diets compared with rats fed the WS
      diets, and it led to a significant rise in Ca and Mg intestinal absorption (Ca
      from 39 to 56 %; Mg from 37 to 60 %). The present model of low-grade metabolic
      acidosis indicates that CP may be effective in alkalinising urine, enhancing
      citrate excretion and ameliorating Ca and Mg balance.

PMID- 16611383
TI  - Inhibitory effects of extractives from leaves of Morus alba on human and rat
      small intestinal disaccharidase activity.
AB  - The inhibitory effect on human and rat intestinal disaccharidase by the
      extractive from the leaves of Morus alba (ELM) containing 0.24 % 1
      deoxynojirimycin equivalent and its inhibitory activities were investigated by
      the modified Dahlqvist method. In the presence of 1000-fold diluted ELM solution,
      the sucrase activity of four human samples was inhibited by 96 % and that of
      maltase and isomaltase by 95 and 99 %, respectively. The activities of trehalase
      and lactase were inhibited by 44 and 38 %, respectively. The human disaccharidase
      activities varied from sample to sample because the samples were obtained from
      different resected regions after surgery. However, the ratio of the inhibitory
      effect for sucrase, maltase, isomaltase, trehalase and lactase was very similar
      among the four samples, and also that of resembled rat intestinal disaccharides.
      The inhibitory constant of the 1-deoxynojirimycin equivalent for sucrase, maltase
      and isomaltase was 2.1 x 10(-4), 2.5 x 10(-4) and 4.5 x 10(-4) mm, respectively,
      and these inhibitory activities were shown, using rat brush border membrane
      vesicles, to be competitive. These results demonstrate that digestion is
      inhibited when an appropriate amount of ELM is orally ingested with sucrose or
      polysaccharide in man. When ELM was orally administered in a sucrose solution to
      fasted rats, the elevation in blood glucose was significantly suppressed,
      depending on the concentration of ELM given. These results suggest that ELM could
      be used as an ingredient in health foods and in foods that help to prevent
      diabetes.

PMID- 16611384
TI  - Hypocholesterolaemic effects of milk-kefir and soyamilk-kefir in cholesterol-fed
      hamsters.
AB  - This study aimed to evaluate the hypocholesterolaemic property of milk-kefir and
      soyamilk-kefir. Male hamsters were fed on a cholesterol-free or cholesterol
      enriched diet containing 10 % skimmed milk, milk-kefir, soyamilk or soyamilk
      kefir for a period of 8 weeks. The soyamilk, milk-kefir and soyamilk-kefir diets
      all tended towards a lowering of serum triacylglycerol and total cholesterol
      concentrations, and a reduction of cholesterol accumulation in the liver, the
      decrease in serum cholesterol concentration being mainly in the non-HDL fraction.
      The soyamilk-kefir diet led to a significant increase in the faecal excretion of
      neutral sterols and bile acids compared with the other two diets. The soyamilk
      kefir diet also elicited a significant decrease in the serum ratio of non-HDL
      cholesterol to HDL-cholesterol, compared with the control, than was the case for
      the other diets. These findings demonstrate that soyamilk-kefir may be considered
      to be among the more promising food components in terms of preventing CVD through
      its hypocholesterolaemic action.

PMID- 16611385
TI  - Effects of dietary cis and trans unsaturated and saturated fatty acids on the
      glucose metabolites and enzymes of rats.
AB  - The aim of the present study was to examine whether the level of dietary cis
      fatty acid (cFA), or the isomers (trans or cis) and/or the saturation of the
      fatty acids at high dietary fat levels altered the intracellular glucose
      metabolites and certain regulatory enzyme activities in the skeletal muscle and
      liver of rats. The animals were fed for 30 d on either a recommended control diet
      (7 % cFA, w/w) or a high-fat diet (20 % fatty acids, w/w). The high-fat diet was
      enriched with either cFA, trans fatty acid (tFA), a moderate proportion of
      saturated fatty acid (MSFA), or a high proportion of saturated fatty acid (HSFA).
      The most striking findings were observed in the gastrocnemius muscle with a HSFA
      diet. There was a significant increase in glucose-6-phosphate (306 %), glucose-1
      phosphate (245 %), fructose-6-phosphate (400 %), fructose-1,6-bisphosphate (86
      %), glyceraldehyde-3-phosphate (38 %), pyruvate (341 %), lactate (325 %), citrate
      (79 %) and the bisphosphorylated sugars as compared with the cFA diet. These
      changes were paralleled by an increase in muscle triacylglycerol content (49 %)
      and a decrease in glucose (39 %). In addition, the amount of cFA and the other
      types of fatty acid (i.e. tFA and MSFA) led to no great differences in glucose
      metabolism as compared with the respective control group. These data support the
      hypothesis that glucose changes induced by a HSFA diet are a multifaceted
      abnormality. Glucose and lactate transport and intracellular glucose metabolism
      could be the key biochemical defects involved in this detrimental effect on
      glucose metabolism.

PMID- 16611386
TI  - NMR-based metabonomic studies reveal changes in the biochemical profile of plasma
      and urine from pigs fed high-fibre rye bread.
AB  - This study presents an NMR-based metabonomic approach to elucidate the overall
      endogenous biochemical effects of a wholegrain diet. Two diets with similar
      levels of dietary fibre and macronutrients, but with contrasting levels of
      wholegrain ingredients, were prepared from wholegrain rye (wholegrain diet (WGD))
      and non-wholegrain wheat (non-wholegrain diet (NWD)) and fed to four pigs in a
      crossover design. Plasma samples were collected after 7 d on each diet, and 1H
      NMR spectra were acquired on these. Partial least squares regression discriminant
      analysis (PLS-DA) on spectra obtained for plasma samples revealed that the
      spectral region at 3.25 parts per million dominates the differentiation between
      the two diets, as the WGD is associated with higher spectral intensity in this
      region. Spiking experiments and LC-MS analyses of the plasma verified that this
      spectral difference could be ascribed to a significantly higher content of
      betaine in WGD plasma samples compared with NWD samples. In an identical study
      with the same diets, urine samples were collected, and 1H NMR spectra were
      acquired on these. PLS-DA on spectra obtained for urine samples revealed changes
      in the intensities of spectral regions, which could be ascribed to differences in
      the content of betaine and creatine/creatinine between the two diets, and LC-MS
      analyses verified a significantly lower content of creatinine in WGD urine
      samples compared with NWD urine samples. In conclusion, using an explorative
      approach, the present studies disclosed biochemical effects of a wholegrain diet
      on plasma betaine content and excretion of betaine and creatinine.

PMID- 16611387
TI  - Total zinc absorption in young women, but not fractional zinc absorption, differs
      between vegetarian and meat-based diets with equal phytic acid content.
AB  - Zn bioavailability is often lower in vegetarian diets mainly due to low Zn and
      high phytic acid contents. The objective of the present study was to determine
      the fractional and total absorption of Zn from a vegetarian diet in comparison
      with meat diets with equal concentrations of phytic acid. A randomized cross-over
      design, comprising three whole-day diet periods of 5 d each, with a vegetarian
      diet or diets containing Polish-produced meat or Danish-produced meat, was
      conducted. Twelve healthy female subjects completed the study. All diets had a
      high content of phytic acid (1250 micromol/d) and in the meat diets the main
      meals contained 60 g pork meat. All main meals were extrinsically labelled with
      the radioactive isotope 65Zn and absorption of Zn was measured in a whole-body
      counter. The mean Zn content of the whole-day diet was: Polish meat diet 9.9 (SE
      0.14) mg, Danish meat diet 9.4 (SE 0.19) mg and vegetarian diet 7.5 (SE 0.18) mg.
      No difference was observed in the fractional absorption of Zn (Polish meat diet:
      27 (SE 1.2) %, Danish meat diet: 27 (SE 1.9) % and vegetarian diet: 23 (SE 2.6)
      %). A significantly lower amount of total Zn was absorbed from the vegetarian
      diet (mean Zn absorption of Polish meat diet: 2.7 (SE 0.12) mg/d (P<0.001),
      Danish meat diet: 2.6 (SE 0.17) mg/d (P=0.006) and vegetarian diet: 1.8 (SE 0.20)
      mg/d). In conclusion, the vegetarian diet compared with the meat-based diets
      resulted in lower amounts of absorbed Zn due to a higher content of Zn in the
      meat diets, but no difference was observed in the fractional absorption of Zn.

PMID- 16611388
TI  - Effects of a policosanol supplement on serum lipid concentrations in
      hypercholesterolaemic and heterozygous familial hypercholesterolaemic subjects.
AB  - Policosanol is a mixture of higher aliphatic primary alcohols that is extracted
      from purified sugar cane wax or a variety of other plant sources, and has been
      shown to have beneficial effects on serum lipid concentrations. The objective of
      this study was to investigate the effects of a policosanol supplement (Octa-60)
      on lipid profiles of hypercholesterolaemic and heterozygous familial
      hypercholesterolaemic subjects. Nineteen hypercholesterolaemic and familial
      hypercholesterolaemic subjects completed this randomised, placebo-controlled,
      double-blind study. The subjects received either a daily dose of 20 mg
      policosanol or placebo for 12 weeks. After a wash-out period of 4 weeks, the
      interventions were crossed over. Lipid levels were measured at baseline and at
      the end of each intervention period. No significant differences in total
      cholesterol and LDL-cholesterol from baseline to end or between policosanol and
      placebo were seen in the hypercholesterolaemic or familial hypercholesterolaemic
      groups. There were small reductions in total cholesterol and LDL-cholesterol from
      baseline to end in the hypercholesterolaemic group, but these changes did not
      differ significantly from the changes with the placebo, indicating that the
      observed decrease in cholesterol in the policosanol group was not due to the
      specific effect of policosanol treatment. The differences in response may be
      ascribed to the differences in composition of the higher aliphatic primary
      alcohols in the previously used products, compared with the local policosanol
      supplement. An intake of 20 mg/d policosanol for 12 weeks had no significant
      effect on serum lipid levels in hypercholesterolaemic and heterozygous familial
      hypercholesterolaemic patients when compared with placebo intake.

PMID- 16611389
TI  - Ascorbic acid supplementation does not attenuate post-exercise muscle soreness
      following muscle-damaging exercise but may delay the recovery process.
AB  - Exercise involving lengthening muscle actions, such as downhill running, results
      in delayed onset muscle soreness (DOMS), which may be attributable to reactive
      oxygen species (ROS). Although exercise causes oxidative stress, any link between
      ROS and DOMS remains speculative. There is emerging evidence to suggest that ROS
      play an important physiological role, assisting in the recovery process and
      protecting the cell from future damage; however, this has not been fully
      established. Despite this uncertainty as to the precise role of ROS, attempts to
      prevent post-exercise ROS production through antioxidant intervention are still
      common. The study investigated the effects of ascorbic acid supplementation on
      ROS production and DOMS following downhill running. Subjects were assigned to two
      groups. The ascorbic acid group (group AA) received 1 g ascorbic acid 2 h pre-,
      and for 14 d post-downhill running, whilst the placebo group (Pl group) received
      a placebo. Blood samples were drawn pre-supplement, pre- and post-exercise, and
      then 1, 2, 3, 4, 7 and 14 d post-exercise for analysis of ascorbate,
      malonaldehyde and total glutathione. DOMS was assessed using a visual analogue
      scale and pressure algometry. Muscle function was assessed using isokinetic
      dynamometry. Plasma ascorbate was elevated throughout in group AA compared with
      the Pl group. Downhill running resulted in DOMS in both groups. Muscle function
      was impaired post-exercise in both groups, although a delayed recovery was noted
      in group AA. Malonaldehyde increased 4 d post-exercise in the Pl group only.
      Ascorbic acid supplementation attenuates ROS production following downhill
      running, without affecting DOMS. Furthermore, ascorbic acid supplementation may
      inhibit the recovery of muscle function.

PMID- 16611390
TI  - Phylloquinone (vitamin K1) intakes and serum undercarboxylated osteocalcin levels
      in Irish postmenopausal women.
AB  - Low phylloquinone (vitamin K1) intakes have been associated with low bone mineral
      density in older adults. Phylloquinone intakes and serum undercarboxylated
      osteocalcin (ucOC) levels were assessed in ninety-seven apparently healthy, free
      living Irish women aged 50-75 years. Phylloquinone intakes were estimated using a
      detailed dietary history, which measured habitual food intakes from a typical 14
      d period, and recently published food composition data for phylloquinone. Fasting
      serum ucOC was measured using an enzyme immunoassay. The median daily intake of
      phylloquinone in the group from all sources was 108.8 microg and from food
      sources only was 106.6 microg, indicating that approximately 99 % of the
      phylloquinone came from food. Vegetables and vegetable dishes contributed 67 % of
      the total phylloquinone intake, but further analysis showed that broccoli,
      cabbage and lettuce were the primary sources, making a total contribution of 44
      %. Twenty per cent of the women had a phylloquinone intake below the UK
      recommendation of 1 microg/kg body weight per day and 34 % failed to meet the US
      Adequate Intake value of 90 microg/day. Mean serum ucOC levels in the women were
      6.2 (SD 1.7) ng/ml and were predicted by phylloquinone intake (beta -2.20,
      generated from log-transformed phylloquinone intake data; P=0.04). On the basis
      of comparisons with both UK recommendations and US Adequate Intakes for
      phylloquinone, the habitual intakes of phylloquinone in a high proportion of
      Irish postmenopausal women may not be adequate.

PMID- 16611391
TI  - High tea consumption diminishes salivary 17beta-estradiol concentration in Polish
      women.
AB  - We hypothesized that among reproductive-age women consuming large quantities of
      tea, the production of estradiol would be suppressed. It has been shown that
      catechins and theaflavines, the major constituents of tea, inhibit aromatase, an
      enzyme which catalyses the conversion of androgens to oestrogens. Our study
      included Polish women living in urban (n 61) and rural (n 48) areas. Women
      collected daily saliva samples for one complete menstrual cycle and filled out
      dietary questionnaires. Saliva samples were analysed by RIA for concentration of
      17beta-estradiol (E2). Women with high (above the median) average daily
      consumption of black tea had reduced levels of salivary E2 in comparison with
      women who drank less black tea (below the median). This effect was observed
      within the whole study group, as well as separately within urban (P=0.0006) and
      rural (P=0.013) groups. High intake of the sum of subclasses of tea catechins and
      epigallocatechin gallate, assessed using the United States Department of
      Agriculture database (http://www.nal.usda.gov), was also associated with lower
      concentrations of E2 within all women (P=0.01 and P=0.0001, respectively) and
      within the urban group (P=0.0001 and P=0.004, respectively). Similar
      relationships were observed between the sum of subclasses of theaflavines and
      thearubigines and E2 levels for the whole group (P=0.002) and for urban women
      (P=0.02). Women with high consumption of tea had lower levels of E2 concentration
      throughout the entire menstrual cycle. These results may have implications for
      reducing hormone-related cancer risk by a relatively easy dietary intervention.

PMID- 16611392
TI  - Evidence for impaired insulin production and higher sensitivity in stunted
      children living in slums.
AB  - The objective of the present study was to investigate the changes in glucose and
      insulin metabolism in nutritionally stunted children that can be involved in the
      appearance of chronic diseases in adulthood. For this purpose, sixty-one children
      were selected, thirty-five boys and twenty-six girls, residents of slums in Sao
      Paulo, Brazil. The children were classified according to the height-for-age as
      stunted (<or=-1.5 Z-score; n 21) or non-stunted (>-1.5 Z-score; n 40). The
      glucose and insulin plasma levels were determined and, from these values, the
      indexes that evaluate the pancreatic beta-cell function (homeostasis model
      assessment (HOMA-B)) and insulin sensitivity (HOMA-S) were assessed. Stunted
      children showed lower values of fasting insulin than those of the non-stunted
      group (boys: 29.7 (SD 14.9) v. 50.4 (SD 29.2) pmol/l, P=0.019; girls: 34.4 (SD
      12.6) v. 62.3 (SD 28.7) pmol/l, P=0.016) but the glucose levels were similar
      (boys: 4.6 (SD 0.3) v. 4.5 (SD 0.3) mmol/l; girls: 4.2 (SD 0.3) v. 4.4 (SD 0.3)
      mmol/l). Stunted children showed lower HOMA-B values (boys: 83 (SD 22) % v. 115
      (SD 36) %, P=0.011; girls: 107 (SD 23) % v. 144 (SD 46) %, P=0.045) and higher
      HOMA-S values (boys: 196 (SD 92) % v. 120 (SD 62) %, P=0.014; girls: 159 (SD 67)
      % v. 98 (SD 57) %, P=0.016). The results show a decreased activity of beta-cell
      function and increased insulin sensitivity in stunted children. The decreased
      beta-cell function of this group may strongly predict type 2 diabetes.

PMID- 16611393
TI  - Differences in the relationship between BMI and percentage body fat between
      Japanese and Australian-Caucasian young men.
AB  - This cross-sectional study aimed to determine ethnic and environmental influences
      on the relationship between BMI and percentage body fat, using a sample of 144
      Japanese and 140 Australian-Caucasian men living in Australia, and eighty-eight
      Japanese men living in Japan. Body composition was assessed by anthropometry
      using standard international methods (International Society for the Advancement
      of Kinanthropometry protocol). Body density was predicted using Durnin and
      Womersley's (1974) equation, and percentage body fat was calculated from Siri's
      (1961) equation. Significant (P<0.05) ethnic differences in stature, body mass
      and BMI were observed between Japanese and Australian men, but no ethnic
      differences were observed in their percentage body fat and height-corrected sum
      of skinfold thicknesses. No differences were found in the BMI-percentage body fat
      relationship between the Japanese subjects living in Australia and in Japan.
      Significant (P<0.05) ethnic differences in the BMI-percentage body fat
      relationship observed from a comparison between pooled Japanese men (aged 18-40
      years, BMI range 16.6-32.8 kg/m2) and Australians (aged 18-39 years, BMI range
      16.1-31.4 kg/m2) suggest that Japanese men are likely to have a greater
      percentage body fat than Australian men at any given BMI value. From the
      analyses, the Japanese men were estimated to have an equivalent amount of body
      fat to the Australian men at BMI values that were about 1.5 units lower than
      those of the Australians (23.5 kg/m2 and 28.2 kg/m2, respectively). It was
      concluded that Japanese men have greater body fat deposition than Australian
      Caucasians at the same BMI value. Japanese men may therefore require lower BMI
      cut-off points to identify obese individuals compared with Australian-Caucasian
      men.

PMID- 16611394
TI  - Childhood obesity treatment: targeting parents exclusively v. parents and
      children.
AB  - There is a consensus that interventions to prevent and treat childhood obesity
      should involve the family; however, the extent of the child's involvement has
      received little attention. The goal of the present study was to evaluate the
      relative efficacy of treating childhood obesity via a family-based health-centred
      intervention, targeting parents alone v. parents and obese children together.
      Thirty-two families with obese children of 6-11 years of age were randomised into
      groups, in which participants were provided for 6 months a comprehensive
      educational and behavioural programme for a healthy lifestyle. These groups
      differed in their main agent of change: parents-only v. the parents and the obese
      child. In both groups, parents were encouraged to foster authoritative parenting
      styles (parents are both firm and supportive; assume a leadership role in the
      environmental change with appropriate granting of child's autonomy). Only the
      intervention aimed at parents-only resulted in a significant reduction in the
      percentage overweight at the end of the programme (P=0.02) as well as at the 1
      year follow-up meeting. The differences between groups at both times were
      significant (P<0.05). A greater reduction in food stimuli in the home (P<0.05)
      was noted in the parents-only group. In both groups, the parents' weight status
      did not change. Regression analysis shows that the level of attendance in
      sessions explained 28 % of the variability in the children's weight status
      change, the treatment group explained another 10 %, and the improvement in the
      obesogenic load explained 11 % of the variability. These results suggest that
      omitting the obese child from active participation in the health-centred
      programme may be beneficial for weight loss and for the promotion of a healthy
      lifestyle among obese children.

PMID- 16611395
TI  - Divergent effects of quercetin conjugates on angiogenesis.
AB  - The present study reports the activities of quercetin and its main circulating
      conjugates in man (quercetin-3'-sulphate (Q3'S) and quercetin-3-glucuronide
      (Q3G)) on in vivo angiogenesis induced by vascular endothelial growth factor
      (VEGF) and examines the effects of these molecules on cultured endothelial cells.
      We found opposing effects of quercetin and its metabolites on angiogenesis. While
      quercetin and Q3G inhibited VEGF-induced endothelial cell functions and
      angiogenesis, Q3'S per se promoted endothelial cell proliferation and
      angiogenesis. The inhibitory effect elicited by Q3G was linked to inhibition of
      extracellular signal-regulated kinases 1/2 (ERK1/2) phosphorylation elicited by
      VEGF. The activation of endothelial cells by Q3'S was associated to stimulation
      of VEGF receptor-2 and to downstream signalling activation (phosphatidylinositol
      3 kinase/Akt and nitric oxide synthase pathways), ultimately responsible for
      ERK1/2 phosphorylation. These data indicate that the effects of circulating
      quercetin conjugates on angiogenesis are different depending on the nature of the
      conjugate. Q3G and Q3'S are the two major conjugates in plasma, but their ratio
      is dependent on several factors, so that inhibition or activation of angiogenesis
      could be subtly shifted as a result of metabolism in vivo.

PMID- 16611396
TI  - Bioethics in human nutrigenomics research: European Nutrigenomics Organisation
      workshop report.
AB  - As part of its work on setting standards and establishing guidelines for
      nutrigenomics research, the European Nutrigenomics Organisation (NuGO) is
      developing bioethical guidelines for those engaged in human nutrigenomics
      studies. A NuGO working group developed a set of draft guidelines addressing four
      areas: (1) information and consenting prior to a nutrigenomics study; (2) the
      generation and use of genotype information; (3) the establishment and maintenance
      of biobanks; (4) the exchange of samples and data. NuGO convened a workshop with
      a panel of invited external experts to assess the draft guidelines. The panel of
      experts confirmed that these areas are important and that the development of
      specific bioethical guidelines for nutrigenomics research would therefore enhance
      the application of established international guidelines in this field of
      biomedical research.

PMID- 16611397
TI  - Subthalamic nucleus stimulation in patients with Parkinson's disease does not
      increase serum ghrelin levels.

PMID- 16611398
TI  - Monounsaturated fatty acid-based lipid emulsions in critically ill patients are
      associated with fewer complications.

PMID- 16611400
TI  - Circulating endothelial cells, endothelial progenitor cells, and endothelial
      microparticles in cancer.
AB  - Cancer, a proliferative disease hallmarked by abnormal cell growth and spread, is
      largely dependent on tumor neoangiogenesis, with evidence of vascular endothelial
      dysfunction. Novel ways to assess vascular function in cancer include measuring
      levels of circulating endothelial cells (CEC). Rare in healthy individuals,
      increased CEC in peripheral blood reflects significant vascular damage and
      dysfunction. They have been documented in many human diseases, including
      different types of cancers. An additional circulating cell population are
      endothelial progenitor cells (EPC), which have the ability to form endothelial
      colonies in vitro and may contribute toward vasculogenesis. At present, there is
      great interest in evaluating the role of EPC as novel markers for tumor
      angiogenesis and drug therapy monitoring. Recently, exocytic procoagulant
      endothelial microparticles (EMP) have also been identified. CEC, EPC, and EMP
      research works may have important clinical implications but are often impeded by
      methodological issues and a lack of consensus on phenotypic identification of
      these cells and particles. This review aims to collate existing literature and
      provide an overview on the current position of CEC, EPC, and EMP in cell biology
      terms and to identify their significance to clinical medicine, with particular
      emphasis on relationship with cancer.

PMID- 16611401
TI  - Lowering of tumor interstitial fluid pressure reduces tumor cell proliferation in
      a xenograft tumor model.
AB  - High tumor interstitial fluid pressure (TIFP) is a characteristic of most solid
      tumors. TIFP may hamper adequate uptake of macromolecular therapeutics in tumor
      tissue. In addition, TIFP generates mechanical forces affecting the tumor cortex,
      which might influence the growth parameters of tumor cells. This seems likely as,
      in other tissues (namely, blood vessels or the skin), mechanical stretch is known
      to trigger proliferation. Therefore, we hypothesize that TIFP-induced stretch
      modulates proliferation-associated parameters. Solid epithelial tumors (A431 and
      A549) were grown in Naval Medical Research Institute nude mice, generating a TIFP
      of about 10 mm Hg (A431) or 5 mm Hg (A549). Tumor drainage of the central cystic
      area led to a rapid decline of TIFP, together with visible relaxation of the
      tumor cortex. It was found by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis and Western blot analysis that TIFP lowering yields a decreased
      phosphorylation of proliferation-associated p44/42 mitogen-activated protein
      kinase and tumor relaxation. In confirmation, immunohistochemical staining showed
      a decrease of tumor-associated proliferation marker Ki-67 after TIFP lowering.
      These data suggest that the mechanical stretch induced by TIFP is a positive
      modulator of tumor proliferation.

PMID- 16611402
TI  - Bioavailability of VEGF in tumor-shed vesicles depends on vesicle burst induced
      by acidic pH.
AB  - Tumor angiogenesis is regulated by a dynamic cross-talk between tumor cells and
      the host microenvironment. Because membrane vesicles shed by tumor cells are
      known to mediate several tumor-host interactions, we determined whether vesicles
      might also stimulate angiogenesis. Vesicles shed by human ovarian carcinoma cell
      lines CABA I and A2780 stimulated the motility and invasiveness of endothelial
      cells in vitro. Enzyme-linked immunosorbent assay and Western blot analysis
      revealed relevant amounts of vascular endothelial growth factor (VEGF) and the
      two matrix metalloproteinases MMP-2 and MMP-9, but not fibroblast growth factor
      2, contained in shed vesicles. An A2780 cell-derived clone transfected to
      overexpress VEGF shed the same amount of vesicles as did a control clone, but
      contained significantly more VEGF within the vesicles. Despite a greater amount
      of VEGF in vesicles of the overexpressing clone, vesicles of both clones
      stimulated endothelial cell motility to comparable levels, suggesting that VEGF
      was stored within the vesicle and was unavailable. Only following vesicle burst
      induced by acidic pH (a characteristic of the tumor microenvironment) was VEGF
      released, leading to significantly higher stimulation of cell motility. Thus,
      tumor-shed membrane vesicles carry VEGF and release it in a bioactive form in
      conditions typical of the tumor microenvironment.

PMID- 16611403
TI  - The role of c-KIT in tumorigenesis: evaluation in canine cutaneous mast cell
      tumors.
AB  - The c-KIT proto-oncogene has been implicated in the pathogenesis of several
      neoplastic diseases, including gastrointestinal stromal tumors and mastocytosis
      in humans, and mast cell tumors (MCTs) in canines. Cutaneous MCTs are common
      neoplasms in dogs and have a variable biologic behavior. The goal of this study
      was to define the prognostic significance of c-KIT mutations identified in canine
      MCTs and the associations between c-KIT mutations, KIT localization, and KIT
      expression levels. Microdissection and polymerase chain reaction were performed
      on 60 MCTs to identify c-KIT mutations. Anti-KIT antibodies were used for
      immunohistochemical evaluation of KIT localization. Forty-two MCTs were included
      in a tissue microarray, and KIT expression was quantified using
      immunofluorescence. Canine MCTs with c-KIT mutations were significantly
      associated with an increased incidence of recurrent disease and death. c-KIT
      mutations were also significantly associated with aberrant protein localization;
      however, the level of KIT expression did not correlate with either c-KIT
      mutations or changes in protein localization. Considering the high prevalence of
      canine MCTs and the central role of c-KIT in the tumorigenesis of certain tumors,
      canine MCTs are an excellent model for characterizing the role of c-KIT in
      neoplastic diseases and is a potential target for novel therapeutic agents in
      clinical trials.

PMID- 16611404
TI  - Prostate tumor growth and recurrence can be modulated by the omega-6:omega-3
      ratio in diet: athymic mouse xenograft model simulating radical prostatectomy.
AB  - Evidence indicates that a diet rich in omega (omega)-6 polyunsaturated fatty
      acids (PUFAs) [e.g., linoleic acid (LA)] increases prostate cancer (PCa) risk,
      whereas a diet rich in omega-3 decreases risk. Precisely how these PUFAs affect
      disease development remains unclear. So we examined the roles that PUFAs play in
      PCa, and we determined if increased omega-3 consumption can impede tumor growth.
      We previously demonstrated an increased expression of an omega-6 LA-metabolizing
      enzyme, 15-lipoxygenase-1 (15-LO-1, ALOX15), in prostate tumor tissue compared
      with normal adjacent prostate tissue, and that elevated 15-LO-1 activity in PCa
      cells has a protumorigenic effect. A PCa cell line, Los Angeles Prostate Cancer-4
      (LAPC-4), expresses prostate-specific antigen (PSA) as well an active 15-LO-1
      enzyme. Therefore, to study whether or not the protumorigenic role of 15-LO-1 and
      dietary omega-6 LA can be modulated by altering omega-3 levels through diet, we
      surgically removed tumors caused by LAPC-4 cells (mouse model to simulate radical
      prostatectomy). Mice were then randomly divided into three different diet groups
      namely, high omega-6 LA, high omega-3 stearidonic acid (SDA), and no fat-and
      examined the effects of omega-6 and omega-3 fatty acids in diet on LAPC-4 tumor
      recurrence by monitoring for PSA. Mice in these diet groups were monitored for
      food consumption, body weight, and serum PSA indicative of the presence of LAPC-4
      cells. Fatty acid methyl esters from erythrocyte membranes were examined for
      omega-6 and omega-3 levels to reflect long-term dietary intake. Our results
      provide evidence that prostate tumors can be modulated by the manipulation of
      omega-6:omega-3 ratios through diet and that the omega-3 fatty acid SDA
      [precursor of eicosapentaenoic acid (EPA)] promotes apoptosis and decreases
      proliferation in cancer cells, causing decreased PSA doubling time, compared to
      omega-6 LA fatty acid, likely by competing with the enzymes of LA and AA
      pathways, namely, 15-LO-1 and cyclooxygenases (COXs). Thus, EPA and DHA (major
      components of fish oil) could potentially be promising dietary intervention
      agents in PCa prevention aimed at 15-LO-1 and COX-2 as molecular targets. These
      observations also provide clues as to its mechanisms of action.

PMID- 16611406
TI  - The role of telomere maintenance in the spontaneous growth arrest of pediatric
      low-grade gliomas.
AB  - Spontaneous tumor regression of pediatric low-grade gliomas (PLGG). We speculated
      that lack of telomere maintenance is responsible for this behavior. We first
      looked for evidence of telomerase activity and alternative lengthening of
      telomeres (ALT) in 56 PLGG. Telomerase activity was observed in 0 of 11 PLGG, in
      contrast to 10 of 13 high-grade pediatric brain tumors. There was no ALT in 45 of
      45 samples. We then applied Q-FISH to eight patients whose indolent PLGG
      underwent two metachronous biopsies over a lag of several years. Telomere
      shortening was observed in the second biopsy in all tumors, but not in normal
      brain control (P < .0001), indicating that lack of telomere maintenance is
      associated with continuous telomere erosion. Based on these observations, we
      found that younger PLGG patients, who exhibit more aggressive and frequently
      recurrent tumors, had significantly longer telomeres than older ones (P =
      .00014). Tumors with a terminal restriction fragment length <7.5 did not recur,
      whereas the presence of longer telomeres (>8.0) conferred a high likelihood of
      late recurrences in PLGG. Our findings provide a plausible biologic mechanism to
      explain the tendency of PLGG to exhibit growth arrest and spontaneous regression.
      Telomere maintenance may therefore represent the first known biologic prognostic
      marker in PLGG.

PMID- 16611405
TI  - Targeted apoptosis activation with GrB/scFvMEL modulates melanoma growth,
      metastatic spread, chemosensitivity, and radiosensitivity.
AB  - GrB/scFvMEL, a fusion protein composed of human granzyme B (GrB) and the single
      chain antibody scFvMEL, targets melanoma gp240 antigen and exerts impressive
      cytotoxic effects by inducing apoptosis. We evaluated the effects of GrB/scFvMEL
      on chemotherapy, radiation therapy, metastasis in vitro, and the growth of human
      melanoma A375 xenograft tumors in nude mice. GrB/scFvMEL showed synergistic
      cytotoxicity when coadministered with doxorubicin, vincristine or cisplatin, and
      additive effects, in combination with etoposide or cytarabine. Optimal cytotoxic
      effects were obtained when cells were treated first with GrB/scFvMEL followed by
      exposure to the agent (rather than the reverse). Pretreatment of A375 cells with
      GrB/scFvMEL significantly sensitized melanoma cells to ionizing radiation
      assessed using a clonogenic survival assay. Subtoxic doses of GrB/scFvMEL
      inhibited the invasion of A375 cells into Matrigel. GrB/scFvMEL (37.5 mg/kg) was
      administered intravenously to nude mice bearing A375 tumors. Saline-treated
      tumors increased 24-fold, whereas tumors treated with GrB/scFvMEL showed a
      significant tumor growth delay increasing four-fold. Tumor tissue displayed an
      increase in apoptotic nuclei compared to control. Thus, the targeted delivery of
      GrB to tumors may have a significant potential for cancer treatment. Targeted
      therapeutic agents specifically designed to impact cellular apoptotic pathways
      may represent a novel class of therapeutic agents.

PMID- 16611407
TI  - Impact of extracellular acidity on the activity of P-glycoprotein and the
      cytotoxicity of chemotherapeutic drugs.
AB  - The expression and activity of P-glycoprotein (pGP) play a role in the multidrug
      resistance of tumors. Because solid-growing tumors often show pronounced hypoxia
      or extracellular acidosis, this study attempted to analyze the impact of an
      acidic environment on the expression and activity of pGP and on the cytotoxicity
      of chemotherapeutic agents. For this, prostate carcinoma cells were exposed to an
      acidic extracellular environment (pH 6.6) for up to 24 hours. pGP activity was
      more than doubled after 3 to 6 hours of incubation in acidic medium, whereas
      cellular pGP expression remained constant, indicating that increased transport
      rate is the result of functional modulation. In parallel, the cytotoxic efficacy
      of daunorubicin showed pronounced reduction at low pH, an effect that was
      reversible on coincubation with a pGP inhibitor. A reduction of intracellular
      Ca2+ concentration by 35% under acidic conditions induced a higher transport rate
      of pGP, an effect comparable to that found on inhibition of protein kinase C
      (PKC). These data indicate that pGP activity is increased by low extracellular pH
      presumably as a result of lowered intracellular calcium levels and inhibition of
      PKC. These findings may explain the reduced cytotoxicity of chemotherapeutic
      agents in hypoxic/acidic tumors.

PMID- 16611408
TI  - Whole transcriptome amplification for gene expression profiling and development
      of molecular archives.
AB  - Expression profiling of clinically obtainable tumor specimens has been hindered
      by the need for microgram quantities of RNA. In vitro transcription (IVT)-based
      amplifications are most commonly used to amplify small quantities of RNA for
      microarray analysis. However, significant drawbacks exist with IVT-based
      amplification, and the need for alternative amplification methods remains.
      Herein, we validate whole transcriptome amplification (WTA), an exponential
      amplification technique that produces cDNA libraries and amplified target in 3 to
      4 hours from nanogram quantities of total RNA using a combination of cDNA
      microarrays and quantitative polymerase chain reaction (PCR). We demonstrate that
      WTA material can serve as a "molecular archive" because a WTA cDNA library can be
      faithfully amplified through multiple rounds of PCR amplification, allowing it to
      serve as a bankable and distributable resource. To demonstrate applicability, WTA
      was combined with laser capture microdissection to profile frozen prostate
      tissues. Unlike most IVT-based and exponential amplification techniques, WTA does
      not depend on the presence of a poly-A tail. Thus, we demonstrate that WTA is
      compatible with artificially degraded RNA and RNA isolated from formalin-fixed
      paraffin-embedded tissues. Taken together, WTA represents a versatile approach to
      profile and archive cDNA from minute tumor samples and is compatible with
      partially degraded RNA.

PMID- 16611410
TI  - Epstein-Barr virus infection alters cellular signal cascades in human
      nasopharyngeal epithelial cells.
AB  - Epstein-Barr virus (EBV) latent infection is a critical event in nasopharyngeal
      carcinoma (NPC) tumorigenesis. EBV-encoded genes have been shown to be involved
      in immune evasion and in the regulation of various cellular signaling cascades.
      To elucidate the roles of EBV in NPC development, stable infection of EBV in
      nasopharyngeal epithelial cell lines was established. Similar to primary tumors
      of NPC, these infected cells exhibited a type II EBV latency expression pattern.
      In this study, multiple cellular signaling pathways in EBV-infected cells were
      investigated. We first demonstrated that in vitro EBV infection resulted in the
      activation of STAT3 and NFkappaB signal cascades in nasopharyngeal epithelial
      cells. Increased expression of their downstream targets (c-Myc, Bcl-xL, IL-6,
      LIF, SOCS-1, SOCS-3, VEGF, and COX-2) was also observed. Moreover, EBV latent
      infection induced the suppression of p38-MAPK activities, but did not activate
      PKR cascade. Our findings suggest that EBV latent infection is able to manipulate
      multiple cellular signal cascades to protect infected cells from immunologic
      attack and to facilitate cancer development.

PMID- 16611409
TI  - (-)-gossypol inhibits growth and promotes apoptosis of human head and neck
      squamous cell carcinoma in vivo.
AB  - Resistance to chemotherapy is a common problem encountered in the treatment of
      head and neck squamous cell carcinoma (HNSCC). Chemoresistant HNSCC tumors
      frequently overexpress antiapoptotic proteins, such as Bcl-x(L). (-)-gossypol,
      the negative enantiomer of a cottonseed polyphenol, binds to Bcl-x(L) and was
      recently been shown to inhibit HNSCC proliferation in vitro. In this study, we
      assessed the in vivo efficacy of (-)-gossypol in an orthotopic xenograft model of
      HNSCC, using two human HNSCC cell lines with high Bcl-x(L) expression levels.
      Both produced tumors in a murine floor-of-mouth model that mimics human HNSCC,
      exhibiting growth and invasion into adjacent tissues. Mice were randomized into
      three groups: vehicle control and two daily intraperitoneal (-)-gossypol
      treatment groups (5 and 15 mg/kg). Tumors were measured twice weekly. In the
      control group, tumors grew progressively, whereas in (-)-gossypol treatment
      groups, tumor growth was significantly suppressed. The mitotic rate in tumors
      from (-)-gossypol-treated animals was significantly lower than that in controls,
      and an increase in the percentage of apoptotic cells was observed in treated
      tumors versus controls. Residual tumors remained growth-suppressed for 2 weeks
      after cessation of (-)-gossypol treatment. Our results demonstrate that (-)
      gossypol can inhibit tumor growth in an orthotopic model of aggressive HNSCC.

PMID- 16611411
TI  - A novel method for gene expression mapping of metastatic competence in human
      bladder cancer.
AB  - Expression profiling by DNA microarray analysis has provided insights into
      molecular alterations that underpin cancer progression and metastasis. Although
      differential expression of microarray-defined probes can be related to numerical
      or structural chromosomal alterations, it is unclear if such changes are also
      clustered in distinct chromosomes or genomic regions and whether chromosomal
      alterations always reflect changes in gene expression. Here we apply the dChip
      algorithm and a novel technique to test the hypothesis that expression changes
      occurring as a function of tumor progression and metastasis are nonrandomly
      distributed. Expression profiling of a human xenograft model of lung metastasis
      phenotype indicates that chromosomes 2, 11, and 20 contain higher percentages of
      differentially expressed genes (P < .05). Furthermore, we show that a number of
      differentially expressed probes mapped to chromosome 17q, defining the existence
      of an expression "hot spot" corresponding to an area of gain determined by
      comparative genomic hybridization (CGH). Interestingly, other areas of gains
      detected by CGH were not associated with expression hot spots. In summary, we
      show that gene expression changes during bladder cancer lung metastasis occur
      nonrandomly in specific chromosomes and intrachromosomal locations.

PMID- 16611413
TI  - Rat tumor response to the vascular-disrupting agent 5,6-dimethylxanthenone-4
      acetic acid as measured by dynamic contrast-enhanced magnetic resonance imaging,
      plasma 5-hydroxyindoleacetic acid levels, and tumor necrosis.
AB  - The dose-dependent effects of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) on rat
      GH3 prolactinomas were investigated in vivo. Dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) was used to assess tumor blood flow/permeability
      pretreatment and 24 hours posttreatment with 0, 100, 200, or 350 mg/kg DMXAA. DCE
      MRI data were analyzed using K(trans) and the integrated area under the
      gadolinium time curve (IAUGC) as response biomarkers. High-performance liquid
      chromatography (HPLC) was used to determine the plasma concentration of the
      serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) following treatment to
      provide an index of increased vessel permeability and vascular damage. Finally,
      tumor necrosis was assessed by grading hematoxylin and eosin-stained sections cut
      from the same tumors investigated by MRI. Both tumor K(trans) and IAUGC were
      significantly reduced 24 hours posttreatment with 350 mg/kg DMXAA only, with no
      evidence of dose response. HPLC demonstrated a significant increase in plasma 5
      HIAA 24 hours posttreatment with 200 and 350 mg/kg DMXAA. Histologic analysis
      revealed some evidence of tumor necrosis following treatment with 100 or 200
      mg/kg DMXAA, reaching significance with 350 mg/kg DMXAA. The absence of any
      reduction in K(trans) or IAUGC following treatment with 200 mg/kg, despite a
      significant increase in 5-HIAA, raises concerns about the utility of established
      DCE-MRI biomarkers to assess tumor response to DMXAA.

PMID- 16611412
TI  - The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer
      patients with infiltrating ductal carcinoma: correlation with important high-risk
      prognostic factors.
AB  - B7-H1 molecule increases the apoptosis of tumor-reactive T lymphocytes and
      reduces their immunogenicity. Breast cancer is the second most common cause of
      mortality after lung cancer. Direct evidence linking B7-H1 with cancer has been
      shown in several malignancies; however, its expression in breast cancer has not
      been investigated. We used immunohistochemistry to investigate the expression of
      the B7-H1 molecule in 44 breast cancer specimens and to study its correlation
      with patients' clinicopathological parameters. The expression of B7-H1 was shown
      in 22 of 44 patients and was not restricted to the tumor epithelium (15 of 44,
      34% in tumor cells), but was also expressed by tumor-infiltrating lymphocytes
      (TIL; 18 of 44, 41%). Interestingly, intratumor expression of B7-H1 was
      significantly associated with histologic grade III-negative (P = .012), estrogen
      receptor-negative (P = .036), and progesterone receptor-negative (P = .040)
      patients. In addition, the expression of B7-H1 in TIL was associated with large
      tumor size (P = .042), histologic grade III (P = .015), positivity of Her2/neu
      status (P = .019), and severe tumor lymphocyte infiltration (P = .001). Taken
      together, these data suggest that B7-H1 may be an important risk factor in breast
      cancer patients and may represent a potential immunotherapeutic target using
      monoclonal antibody against the B7-H1 molecule.

PMID- 16611414
TI  - Noninvasive MRI of endothelial cell response to human breast cancer cells.
AB  - We have developed a noninvasive magnetic resonance imaging (MRI) assay to
      characterize human umbilical vein endothelial cell (HUVEC) motility, invasion,
      and network formation in response to the presence of cancer cells. HUVECs were
      labeled with a superparamagnetic iron oxide T(2) contrast agent and cocultured
      with MDA-MB-231 breast cancer cells in the presence of an extracellular matrix
      (ECM) gel. Invasion into the ECM gel by HUVECs in response to paracrine factors
      secreted by MDA-MB-231 cancer cells, as well as network formation by HUVECs, was
      easily tracked with MRI. The invasive behavior of HUVECs was not observed in the
      absence of cancer cells. This noninvasive assay used to characterize the response
      of endothelial cells (ECs) can be used to understand the role of proangiogenic or
      antiangiogenic stimuli, and to study the interactions between ECs and other
      disease-specific cells in pathologies with aberrant angiogenesis, such as
      retinopathy and arthritis.

PMID- 16611415
TI  - Nanoparticle imaging of integrins on tumor cells.
AB  - Nanoparticles 10 to 100 nm in size can deliver large payloads to molecular
      targets, but undergo slow diffusion and/or slow transport through delivery
      barriers. To examine the feasibility of nanoparticles targeting a marker
      expressed in tumor cells, we used the binding of cyclic arginine-glycine-aspartic
      acid (RGD) nanoparticle targeting integrins on BT-20 tumor as a model system. The
      goals of this study were: 1) to use nanoparticles to image alpha(V)beta3
      integrins expressed in BT-20 tumor cells by fluorescence-based imaging and
      magnetic resonance imaging, and, 2) to identify factors associated with the
      ability of nanoparticles to target tumor cell integrins. Three factors were
      identified: 1) tumor cell integrin expression (the alpha(V)beta3 integrin was
      expressed in BT-20 cells, but not in 9L cells); 2) nanoparticle pharmacokinetics
      (the cyclic RGD peptide cross-linked iron oxide had a blood half-life of 180
      minutes and was able to escape from the vasculature over its long circulation
      time); and 3) tumor vascularization (the tumor had a dense capillary bed, with
      distances of <100 microm between capillaries). These results suggest that
      nanoparticles could be targeted to the cell surface markers expressed in tumor
      cells, at least in the case wherein the nanoparticles and the tumor model have
      characteristics similar to those of the BT-20 tumor employed here.

PMID- 16611416
TI  - Soluble HLA-G molecules increase during acute leukemia, especially in subtypes
      affecting monocytic and lymphoid lineages.
AB  - Human leukocyte antigen G (HLA-G) molecules exhibit immunomodulatory properties
      corresponding to nonclassic class I genes of the major histocompatibility
      complex. They are either membrane-bound or solubly expressed during certain
      tumoral malignancies. Soluble human leukocyte antigen G (sHLA-G) molecules seem
      more frequently expressed than membrane-bound isoforms during hematologic
      malignancies, such as lymphoproliferative disorders. Assay of these molecules by
      enzyme-linked immunosorbent assay in patients suffering from another hematologic
      disorder (acute leukemia) highlights increased sHLA-G secretion. This increased
      secretion seems more marked in acute leukemia subtypes affecting monocytic and
      lymphoid lineages such as FABM4 and FABM5, as well as both B and T acute
      lymphoblastic leukemia (ALL). Moreover, this study uses in vitro cytokine
      stimulations and reveals the respective potential roles of granulocyte-macrophage
      colony-stimulating factor and interferon-gamma in increasing this secretion in
      FABM4 and ALL. Correlations between sHLA-G plasma level and clinical biologic
      features suggest a link between elevated sHLA-G level and 1) the absence of
      anterior myelodysplasia and 2) high-level leukocytosis. All these findings
      suggest that sHLA-G molecules could be a factor in tumoral escape from immune
      survey during acute leukemia.

PMID- 16611418
TI  - Couples' experiences of the support process in depression: a phenomenological
      analysis.
AB  - This qualitative, phenomenological study examined how partners attempted to
      support a depressed spouse and how each member of the couple experienced the
      support process. Participants were nine people who were or had been depressed,
      who were interviewed jointly with their partners on two separate occasions. The
      interviews, analysed using interpretative phenomenological analysis, yielded 10
      themes, grouped into two domains. The first domain related to the challenges
      couples faced over the trajectory of a depressive episode, and the second related
      to issues in the support process, as experienced by each member of the couple.
      Couples' accounts of the support process were characterized by a pervasive sense
      of bewilderment and struggle. The findings underline the importance of including
      the partner in psychological interventions for depression.

PMID- 16611417
TI  - Melanocyte transformation associated with substrate adhesion impediment.
AB  - Exclude experimental models of malignant transformation employ chemical and
      physical carcinogens or genetic manipulations to study tumor progression. In this
      work, different melanoma cell lines were established after submitting a
      nontumorigenic melanocyte lineage (melan-a) to sequential cycles of forced
      anchorage impediment. The great majority of these cells underwent anoikis when
      maintained in suspension. After one deadhesion cycle, phenotypic alterations were
      noticeable in the few surviving cells, which became more numerous and showed
      progressive alterations after each adhesion impediment step. No significant
      differences in cell surface expression of integrins were detected, but a clear
      electrophoretic migration shift, compatible with an altered glycosylation
      pattern, was observed for beta1 chain in transformed cell lines. In parallel, a
      progressive enrichment of tri- and tetra-antennary N-glycans was apparent,
      suggesting increased N-acetylglucosaminyltransferase V activity. Alterations both
      in proteoglycan glycosylation pattern and core protein expression were detected
      during the transformation process. In conclusion, this model corroborates the
      role of adhesion state as a promoting agent in transformation process and
      demonstrates that cell adhesion disturbances may act as carcinogenic stimuli, at
      least for a nontumorigenic immortalized melanocyte lineage. These findings have
      intriguing implications for in vivo carcinogenesis, suggesting that anchorage
      independence may precede, and contribute to, neoplastic conversion.

PMID- 16611419
TI  - The child's active role in mother-child, father-child psychotherapy: a
      psychodynamic approach to the treatment of relational disturbances.
AB  - The short-term mother-child and father-child psychoanalytic psychotherapy assumes
      that children develop specific types of relationships with each parent, as well
      as with the parenting couple. The model integrates an intra-psychic, object
      relational view with an interpersonal perspective to the treatment of relational
      disturbances in childhood. The same therapist meets with the mother-child, father
      child dyads on a weekly basis, along with regular meetings with the parental
      dyad. The model focuses on the developmentally prelatency child's need for the
      active participation of both parents in the here-and-now shared experiences of
      the therapeutic process. The participants express, in interactions and in
      enactments, various contents and meanings of their specific patterns of
      relations. The therapist addresses the behaviours as well as the meanings of
      relations, thus promoting reflective understanding and experiential changes in
      self, other, and self-other relations. The child's active and different
      participation with each parent is the main change-promoting factor. The child
      uses mainly the medium of play to express his/her needs and to mobilize the
      therapist's help. The therapist's access to the different dyads is utilized to
      better understand the explicit and implicit relational themes. The therapist
      supports the co-construction of new and different behaviour patterns and the co
      creation of additional meanings to representations. The setup fosters the child's
      active participation in each dyad's growth-promoting changes.

PMID- 16611420
TI  - Interpersonal sensitivities: their links to mood, anger and gender.
AB  - This paper explores two interpersonal sensitivities (to rejection and to social
      put-down) in a group of 54 depressed men and 50 depressed women. Measures of
      anhedonia, anxiety, anger, social comparison, and submissive behaviour were also
      obtained. We found no differences in rejection sensitivity, anger, anhedonia, or
      anxiety between the sample of depressed men and women. Depressed women rated
      themselves as more submissive and more inferior than depressed men, and blamed
      themselves more for being criticized and put-down by other people. Principal
      components analysis (PCA) revealed three underlying factors: mood (including
      anxiety and depression), internalization (related to self-blame and feelings of
      low rank), and externalization (related to anger and blaming others for
      criticism). For both men and women internalization was significantly correlated
      with depression. However, externalization was negatively related to depression in
      women, but positively related to depression in men.

PMID- 16611421
TI  - Narrative as an outcome domain in psychosis.
AB  - A recent renewed interest in psychosocial treatments for psychosis has only
      minimally included considerations of narrative therapy and other interventions
      based in post-modernism. This lack of attention is curious given the profound
      narrative disruptions often seen in psychotic illness. In this review article we
      describe several studies in which narratives and narrative dimensions have been
      utilized to assess outcomes in psychosis. Valid and reliable measures of
      narrative change in psychosis are possible and can coexist with and complement
      traditional outcome measures. Perhaps more significantly, considerations of
      narrative changes may offer unique insights into the process of recovery from
      psychosis as well as leading to beneficial psychosocial treatments for the same.

PMID- 16611422
TI  - Remembered parenting style and psychological well-being in young adults whose
      parents had experienced early child loss.
AB  - BACKGROUND: Pre-, peri-, or postnatal childloss can have devastating consequences
      for bereaved families. This study explored the long-term sequelae of these
      experiences for the young adult siblings' psychological well-being and the
      perceived quality of parenting received during participants' first 16 years of
      life. METHODS: A bereaved group of young adult siblings was compared to a non
      bereaved group on the Parent Bonding Instrument, the Rosenberg Self-esteem Scale
      and the Mental Health Index-5. RESULTS: The loss group reported their mothers,
      but not their fathers, to have been more protective/controlling than non-bereaved
      participants. No differences between the loss group and the comparison group were
      found for parental care, their own mental health or self-esteem. Those
      participants whose siblings died during the peri/post-natal period perceived
      their parents as more controlling than the miscarriage group as well as the non
      bereaved group. Higher protection scores were evident among those born subsequent
      to the loss than those who were born before. Lower levels of protection were
      associated with better mental health across all groups. In the non-bereaved group
      lower levels of protection were associated with better self-esteem, but in the
      bereaved group a different even opposite pattern was shown. CONCLUSIONS: Young
      adults who lost a sibling when they themselves were under 5 recall their mothers
      as more protective/controlling than non-bereaved groups, although they do not
      report less care nor differ in mental health nor self-esteem. Higher levels of
      parental protection/control were found where the child was born subsequent to
      loss and for peri/post-natal loss rather than miscarriage. While high protection
      was associated with poorer mental health regardless of loss this may not be
      necessarily disadvantageous to the child's self-esteem. Differences with regard
      to parent gender were found.

PMID- 16611423
TI  - The 20-item Toronto Alexithymia Scale: validation of factor solutions using
      confirmatory factor analysis on physiotherapy out-patients.
AB  - OBJECTIVE: Whilst the 20-item Toronto Alexithymia Scale (TAS-20) was developed to
      measure three intercorrelated dimensions, there is some debate as to whether the
      scale is best served by a two- or three-factor construct. In particular, there is
      some doubt as to whether clinical data exhibit the third factor. This study uses
      data from a sample of physiotherapy (physical therapy) out-patients in the UK to
      validate the factorial structure of a set of models postulated in the literature,
      including the three-factor model hypothesized by Bagby et al. (1994). METHOD:
      Data were collected from a sample of physiotherapy out-patients (N=242).
      Specialist factor analysis software (LISREL 8.54) was used to perform
      confirmatory factor analyses on a range of models proposed in the literature.
      RESULTS: The analysis supports the three-factor model assumed by Bagby et al.
      (1994), as well as most of the two-factor models suggested in the literature.
      CONCLUSIONS: This new set of clinical data supports most of the two- and three
      factor models postulated in the recent literature, including the three-factor
      model advocated by Bagby et al. (1994).

PMID- 16611424
TI  - Young adults in psychoanalytic psychotherapy: patient characteristics and therapy
      outcome.
AB  - The aims of this naturalistic study are to present patient characteristics and
      analyse various outcome measures at termination for psychoanalytic
      psychotherapies with young adults. Patients (n = 134) between 18 and 25 years
      were included, of whom 92 received individual and 42 group therapy. One third had
      a self-reported personality disorder. The patients were considerably more
      troubled than Swedish norm groups at intake and they showed improvement on all
      outcome measures during therapy. However, the post therapy means did not fully
      reach the norm group means. The largest positive changes (pre- versus post
      therapy) were with respect to the patients' overall health and functioning.
      Changes were more moderate in self-reported symptoms, self-concept, and self
      representation, while changes in interpersonal problems and object
      representations were small. The results of this study are discussed in the
      context of advantages and disadvantages of naturalistic versus randomized
      controlled study designs.

PMID- 16611425
TI  - Therapists' recall of early sudden gains in routine clinical practice.
AB  - This study followed up one by Stiles et al. (2003), which identified sudden gains
      -- large reductions from one session to the next on a short form of clinical
      outcomes in routine evaluation outcome measure (CORE-SF) -- by some clients in
      routine clinical practice. We interviewed the therapists who had treated sudden
      gain and non-sudden gain clients. Results showed that therapists could
      retrospectively identify which clients had or had not experienced sudden CORE-SF
      gains at substantially better than chance rates, although they identified only
      about half of the clients who had experienced such gains.

PMID- 16611426
TI  - I feel like a scrambled egg in my head: an idiographic case study of meaning
      making and anger using interpretative phenomenological analysis.
AB  - What does it feel like when one's meaning making is impoverished and threatens to
      break down? The aim of this study is to show how meaning making is achieved in
      the context of one's life and how this achievement is often a struggle for the
      individual. The study reports data from semi-structured interviews with a female
      participant, which was analysed using interpretative phenomenological analysis
      (IPA). This paper examines how cultural discourses and conventions are
      experienced and given meaning by the individual. First, the analysis demonstrates
      how dominant discourses are used to explain anger and aggression. These include
      hormones, alcohol, and the influence of past relationships on present action.
      Second, it examines how the participant's meaning making is often ambiguous and
      confused, and how she variously accepts and challenges available meanings.
      Finally, the analysis demonstrates how meaning making can break down and the
      consequences of this for the individual's sense of self.

PMID- 16611427
TI  - A naturalistic comparison of the effectiveness of trainee and qualified clinical
      psychologists.
AB  - OBJECTIVE: To compare the effect of clinician type on the outcome for adult
      mental health clients treated by trainee and qualified clinical psychologists.
      DESIGN: Naturalistic, non-random between-participants group design: a group of 60
      adult mental health out-patients treated by trainees and a matched group of 60
      patients treated by qualified clinical psychologists. METHOD: Participants
      completed a range of established measures at assessment and outcome of their
      treatment during routine clinical practice. RESULTS: Significant improvements in
      mental health were made for both groups from assessment to outcome; however, no
      significant effect of clinician type was evident. CONCLUSIONS: A variety of
      factors (e.g. quantity of supervision) contributing to trainee effectiveness are
      identified and discussed.

PMID- 16611433
TI  - Aspire (Asia Pacific Initiative on Reproductive Endocrinology): Optimizing
      infertility management in Asia. Changsha, Hunan, China, 31 March - 2 April 2006.
      Abstracts.

PMID- 16611434
TI  - HIV/AIDS and TB.

PMID- 16611435
TI  - HIV-TB: epidemiology, clinical features and diagnosis of smear-negativeTB.
AB  - TB remains an important public health problem in the world that has been
      exacerbated by the HIV epidemic. In 2000, while 9% of new TB infections worldwide
      were attributable to HIV, in Sub-Saharan Africa--a region with higher HIV
      prevalence--about 31% of new TB cases were attributable to HIV. Clinical
      presentation of TB in HIV-infected individuals depends on the severity of the
      suppression of immunological functions. In patients in early stages of HIV
      infection, TB clinical presentation resembles that of HIV-negative individuals
      with more pulmonary involvement and localized lesions. With the progressive
      suppression of immunological functions, TB tends to be more generalized affecting
      more than one organ. Classic TB symptoms are non-specific and may result in
      delayed diagnosis or misdiagnosis. Diagnosis of smear negative pulmonary TB is
      based on clinical and radiological features. Sputum culture and rapid diagnostic
      tests based on polymerase chain reaction can be used where available.

PMID- 16611436
TI  - HIV testing in patients with TB.

PMID- 16611437
TI  - Antiretroviral therapy and TB.
AB  - With the expansion and convergence of the HIV and TB epidemics worldwide,
      clinicians will increasingly will be called to manage and treat co-infected
      patients. TB and HIV medications have overlapping and additive toxicities that
      can complicate therapy. Additional clinical challenges include choice of optimal
      first and second line antiretroviral therapy, appropriate timing of
      antiretroviral initiation, management of immune reconstitution disease, and TB
      diagnosed after initiation of HIV therapy. Despite the complexities presented by
      co-infection, many programmes have integrated care and are successfully treating
      patients with both HIV and TB.

PMID- 16611438
TI  - Cotrimoxazole prophylaxis for HIV-positive TB patients in developing countries.
AB  - Despite provisional recommendations from the World Health Organization and UNAIDS
      that cotrimoxazole (CTX) prophylaxis be offered to all individuals living with
      AIDS, including HIV-positive patients with TB, its routine use in developing
      countries particularly Africa has been minimal. Concerns were expressed regarding
      its effectiveness in areas of high bacterial resistance, that its widespread use
      might substantially increase bacterial cross-resistance in the community and that
      this intervention might promote resistance of malaria parasites to sulphadoxine
      pyrimethamine. We review the current evidence on the above concerns and highlight
      the main operational considerations related to implementing CTX prophylaxis as a
      basic component of care for HIV-positive TB patients in developing countries.

PMID- 16611439
TI  - Isoniazid to prevent first and recurrent episodes of TB.

PMID- 16611440
TI  - Rate, pattern and barriers of HIV serostatus disclosure in a resource-limited
      setting in the Niger delta of Nigeria.
AB  - The disclosure of HIV serostatus is a difficult emotional task creating
      opportunity for both support and rejection. In this study, we evaluated the rate,
      patterns and barriers to HIV serostatus disclosure. A pre-tested interviewer
      administered questionnaire from 187 HIV infected people residing in a resource
      limited setting in the Niger Delta of Nigeria was analysed. Of the 187 HIV
      seropositive patients studied, 144 (77.0%) had disclosed their HIV-serostatus
      while 43 (23.0%) had not. Results showed that the patients had disclosed their
      HIV-serostatus to: parents (22.3%), siblings (9.7%), pastors (27.8%), friends
      (6.3%), family members (10.4%) and sexual partners (23.6%) (P = 0.004). Females
      were more likely (59.7%) to disclose their HIV serostatus compared with males
      (40.3%) (P = 0.003). Mothers were twice as likely (65.6%) to be confided in
      compared with fathers. Barriers to HIV serostatus disclosure included fear of
      stigmatization, victimization, fear of confidants spreading the news of their
      serostatus and fear of accusation of infidelity and abandonment (P = 0.002).
      Married respondents were more likely to disclose their status. Better-educated
      respondents with tertiary education were more likely to disclose their HIV
      serostatus. Expectation of economic, spiritual, emotional and social support was
      the major reason for disclosure. The ratio of disclosure to non-disclosure among
      patients with non-formal education was (2.6:1.0), primary education (2.3:1.0),
      secondary education (3.3:1.0) and tertiary education (10.0:1.0). Disclosure of
      HIV serostatus can foster economic social and economic support. There is need for
      the re-intensification of interventional measure that combines provider, patients
      and community education particularly in the aspect of anti-stigma campaign,
      partner notification and skill building to facilitate appropriate HIV serostatus
      disclosure.

PMID- 16611441
TI  - The risk factors for relapse among patients with African trypanosomiasis in
      Daloa, Cote d'Ivoire.
AB  - We describe rates of follow-up and the risk factors for relapse in a cohort of
      adult patients treated for Trypanosoma brucei gambiense African trypanosomiasis.
      812 patients were discharged from hospital between 6 January 1983 and 16 January
      1992. The numbers who did not attend a scheduled follow-up appointment at 6,12,18
      and 24 months were 383 (47%), 467 (58%), 536 (66%) and 533 (66%), respectively.
      Thirty-two patients relapsed over the 2 years follow-up: 24 (75%) before the 12
      month follow-up appointment. The presence of antibody to trypanosomes in the
      cerebrospinal fluid (CSF) at discharge from hospital was associated significantly
      with the risk of relapse at any time. When the analysis was restricted to a
      follow-up of 1 year, a protein level in the CSF above the median and the presence
      of antibody in the CSF (both at discharge) were associated in univariate analysis
      with relapse. A high number of patients were lost to follow-up, which may have
      resulted in bias. From the data available, the majority of the relapses were
      recorded within 12 months and the presence of antibody in the CSF at hospital
      discharge was identified as an independent predictor of future relapse at any
      time.

PMID- 16611442
TI  - Existence of antimalarial formulations with low bioavailability in Tanzania.
AB  - The main objective of this work was to assess the relative bioavailability of two
      tablet formulations containing sulfadoxine/pyrimethamine (SP) and marketed in
      Tanzania. Twelve healthy volunteers were randomized to receive a single oral dose
      of three SP tablets each containing 500 mg sulfadoxine (SDX) and 25 mg
      pyrimethamine (PYR) in a form of either A (a locally manufactured SP tablet
      formulation, manufactured by a local pharmaceutical industry in Tanzania) or B
      (Fansidar), Hoffmann La Roche, Basel, Switzerland, an innovator's SP) after an
      overnight fasting. Serial blood samples (100 microL) were collected from a finger
      prick in duplicate up to 10 days and dried on Whatman filter paper. The samples
      were assayed for SDX and PYR using high-performance liquid chromatographic
      methods. Pharmacokinetic parameters of SDX and PYR were estimated by single
      compartment method. The pharmacokinetics of formulation A--maximum plasma
      concentration, the areas under the plasma concentration--time curve and the
      relative bioavailability (A versus B) were significantly lower than those of
      formulation B (P < 0.1). These observed differences indicate bioinequivalence
      between the two products.

PMID- 16611443
TI  - Pattern of presentation of primary open-angle glaucoma in Benin City, Nigeria.
AB  - Late presentation is a major problem in the management of patients with primary
      open-angle glaucoma. The aim of this study was to determine the clinical features
      and the degree of visual disability of glaucoma patients at initial presentation.
      This was a prospective study of new patients with a diagnosis of primary open
      angle glaucoma seen between January 2001 and August 2002 at the University of
      Benin Teaching Hospital, Nigeria. The patients were analysed in the context of
      age, gender, geographical abode, educational and socioeconomic status and
      clinical presentation. The patients were examined using the Snellen's chart, pen
      torch, slit lamp biomicroscopy, ophthalmoscopy, tonometry, perimetry and
      gonioscopy. Over a 20-month period 154 patients were studied; the mean age was
      52.73 years (standard deviation +/- 15.98) and the highest incidence was in the
      seventh decade. The male to female ratio was 2.1:1. In all, 119 patients (77.3%)
      presented with subjective visual loss in one or both eyes, while 57.1% dated the
      onset of their symptoms to 1-5 years before presentation. Overall, 38 patients
      (24.7%) were blind when using visual acuity as the criteria, while 87 patients
      (56.5%) were blind when using visual fields as the criteria. The problem of late
      presentation has not improved over the last two and a half decades. More measures
      towards early detection by extensive health education, screening programmes and
      training of more eye care providers need to be put in place.

PMID- 16611444
TI  - Risk factors of postpartum depression and EPDS scores in a group of Nigerian
      women.
AB  - A sample of 252 women was studied for postpartum depression (PPD) in a 68-bed
      maternity hospital in Lagos, Nigeria. After obtaining consent, they were assessed
      using: (1) a questionnaire on socio-demographic profile and risk factors of PPD;
      (2) the Edinburgh Postnatal Depression Scale (EPDS), and when necessary with (3)
      the depressive module of International Classification of Diseases, 10th edition
      (ICD-10). The cohort was predominantly young (mean age 28.5 +/- 5.26 years).
      About one-quarter (23%) scored > or =12, (the cut-off score) on EPDS assessment;
      with majority of these depressed on further evaluation with ICD-10. The risk
      factors for PPD were found to be mainly psychosocial, including unwanted
      pregnancy, unemployment and marital conflict. It is concluded that PPD is a major
      complication of childbirth in Nigeria, which can be minimized by improving both
      the citizens' socioeconomic condition and providing cheaper and more efficient
      health-care services.

PMID- 16611445
TI  - Use of a fiberoptic cystoscope to facilitate intubation in a difficult airway.

PMID- 16611446
TI  - Seroprevalence of human immunodeficiency virus among blood donors in Northwest
      Ethiopia, 1995-2002.
AB  - Data on age, sex, occupation, HIV serostatus and year of donation were collected
      from the blood donors log book of Gondar College of Medical Sciences Hospital,
      Northwest Ethiopia, for the period between January 1995 and December 2002 and
      analysed. The crude HIV seroprevalence was 9.9% (1109/11,204). A declining trend
      in the prevalence was observed from as high as 15.7% (207/1321) in 1995 to 9.3%
      (123/1327) in 1999 and down to 4.3% (68/1576) in 2002. The declining trend
      observed in recent years is encouraging and should further be strengthened by
      making use of the blood bank as an entry point for HIV testing and counselling
      services.

PMID- 16611447
TI  - Comparison of salivary and serum antibody detection in HIV-1 infection by ELISA
      and rapid methods in India.

PMID- 16611448
TI  - Spectrum of eye disorders among diabetes mellitus patients in Gaborone, Botswana.
AB  - This cross-sectional study was designed to determine the spectrum and prevalence
      of eye disorders among diabetes mellitus (DM) patients in Gaborone, Botswana. All
      DM patients who attended Gaborone City Council (GCC) health facilities underwent
      eye examination at the specialist eye clinic. All of the study participants were
      interviewed using questionnaires and underwent laboratory investigations. A total
      of 401 DM patients participated in the study. About 60 % never had an eye
      examination before. Refractive error (29.2%) was the most prevalent followed by
      cataract (20.2%), retinopathy (9.2%), pterygeum (6.7%), glaucoma (2.5%) and
      keratopathy (0.7%). The study showed that DM patients are affected by many eye
      disorders other than diabetic retinopathy and regular eye examination should be
      part of diabetic care.

PMID- 16611449
TI  - Oral health in rural South African type 2 diabetic patients.
AB  - Diabetes increases the risk of periodontal disease, but information from the
      tropics is lacking, and the relationship between periodontal disease and
      glycaemic control is uncertain. We examined 23 type 2 diabetic patients in a
      rural and resource-poor area of South Africa. Mean age was 59 +/- 10 (1SD) years,
      and diabetes duration 6 +/- 6 years. In all,11 were 'well controlled'
      (glycosylated haemoglobin (HbA1c) < 8.0%, mean 6.5%), and 12 'poorly controlled'
      (HbA1c > 8.0%, mean 13.0%). Periodontal disease was more common in the poorly
      controlled group (42% versus 18%, P < 0.002). We conclude that dental health is
      poor in type 2 diabetic patients in rural Africa, and that periodontal disease is
      closely related to glycaemic control. Improved dental and diabetes care is needed
      in such communities.

PMID- 16611450
TI  - Percutaneous needle pleural biopsies in pleural effusion of uncertain aetiology
      in a Nigerian teaching hospital.
AB  - Clinical observation shows that most of the patients with pleural effusion of
      undetermined aetiology in a Nigerian teaching hospital receive antiTB drug
      trials. This observation prompted the authors to evaluate the role of
      percutaneous needle pleural biopsy as a diagnostic tool in effusions of uncertain
      aetiology. Thirty-seven patients with pleural effusion of uncertain aetiology
      were investigated by percutaneous pleural biopsies using Abrams pleural biopsy
      needle over an 18-month period. In 34, the aetiology was established giving a
      sensitivity of 92%. Non-specific pleurisy/empyema remains the commonest cause of
      effusion (41%), followed closely by malignancies (29.4%) and TB pleurisy (22%),
      respectively. Percutaneous needle pleural biopsies establish diagnosis of
      malignancy in 91% of the cases with 72% of the malignancies originating from the
      lung. There is a significant association between malignancy and pleural effusion
      of uncertain aetiology in patients above 40 years of age (P = 0.022). The
      empirical use of antiTB drugs in the absence of investigative results suggestive
      of the diagnoses should be discouraged. Instead concerted effort should be made
      to establish the cause of such effusion.

PMID- 16611451
TI  - Does long-term chloramphenicol cause anaemia in Malawi?
AB  - Common clinical practice in many tropical paediatric departments is that
      chloramphenicol courses are limited to 2 weeks due to concerns about anaemia.
      However, this approach is not supported by current research and animal models. We
      used chloramphenicol for 6 weeks in 146 children with septic arthritis. All the
      children improved clinically. Most children were anaemic on presentation (mean
      haemoglobin [Hb] 8.43 SD 1.9), but the anaemia improved rapidly with clinical
      resolution of the infection and was maintained at 6 months after presentation
      (mean Hb 10.57 SD 1.86).

PMID- 16611452
TI  - Rabies and antirabies immunization in South Western Nigeria: knowledge, attitude
      and practice.
AB  - Factors responsible for the continued endemicity of rabies in Nigeria were
      determined by carrying out a knowledge, attitude and practice study among
      residents of Osun State. Structured questionnaires were administered to 679
      individuals comprising students, traders and civil servants. Only 33.4% of the
      respondents knew rabies could be prevented by vaccination, while 38.7% believed
      that the infection could be treated with herbs. Of the 387 victims of dog bite,
      240 (62%) never sought prophylactic postexposure treatment. Of the 10 people who
      received postexposure treatment, only one received the appropriate treatment
      consisting of washing, disinfection of wounds, tetanus toxoid and complete
      antirabies immunization.

PMID- 16611453
TI  - Cardiopulmonary manifestations of typhoid fever: a prospective analysis of 65
      cases in Iran.
AB  - For an evaluation of cardiopulmonary manifestations in typhoid in Iran, we
      studied 65 patients with positive blood or bone marrow culture for Salmonella
      typhi during a 2-year period. Cardiac complications were seen in 4.6%
      (myocarditis, pericarditis, pulmonary emboli) and pulmonary complications in
      6.2%.

PMID- 16611454
TI  - Parotid TB.
AB  - TB of the parotid is rare and only about 100 cases have been reported in the
      world literature. Often the diagnosis is made only after the surgery performed
      for a suspected neoplasm. We describe three patients with diffuse form of
      parotidTB without any evidence of tubercular focus elsewhere. Fine needle
      aspiration cytology confirmed the diagnosis in two cases, while the third case
      was diagnosed only after surgery.

PMID- 16611455
TI  - Hepatic TB: four cases and a review of the literature.

PMID- 16611456
TI  - The aetiology of angular deformities of the lower limb in children in Malawi: a
      review of 35 patients.
AB  - The aetiology of 35 Malawian children with angular deformities of the lower limb,
      including 18 with varus,13 with valgus and four with windswept deformities, was
      assessed prior to surgical correction by proximal tibial or distal femoral
      osteotomies. Among the varus limbs, the aetiologies were ligamentous laxity of
      the knee (7), lesions of the medial tibial metaphysis (3), bowing of the femora
      and tibiae (3), and there were two girls with the end stage of Blount's disease.
      Among the valgus patients, eight had extremes of physiological knock knee and
      five had valgus bowing of the femora or tibiae.

PMID- 16611458
TI  - Pattern and outcome of TB in children receiving directly observed treatment in
      Sagamu: a 5-year review.

PMID- 16611459
TI  - Oral candidiasis in HIV-infected patients and its relation to CD4 + counts: an
      adjunct clinical marker of HIV disease progression.

PMID- 16611460
TI  - Sero prevalence of hepatitis B surface antigen (HBsAg) in pregnant women in
      Southeast Nigeria.

PMID- 16611461
TI  - Genotype x Environment interaction in psychopathology: fact or artifact?
AB  - Recent studies have claimed to detect interaction between candidate genes and
      specific environmental factors (Genotype x Environment interaction, G x E) in
      susceptibility to psychiatric disorder. The objective of the present study was to
      examine possible artifacts that could explain widely publicized findings. The
      additive effects of candidate genes and measured environment on liability to
      disorder were simulated under a model that allowed for mixture of distributions
      in liability conditional on genotype and environment. Simulated liabilities were
      dichotomized at a threshold value to reflect diagnosis of disorder. Multiple
      blocks of simulated data were analyzed by standard statistical methods to test
      for the main effects and interactions of genes and environment on outcome. The
      main outcome of this study was simulated liabilities and diagnoses of major
      depression and antisocial behavior. Analysis of the dichotomized data by logistic
      regression frequently detected significant G x E interaction even though none was
      present for liability. There is therefore reason to question the biological
      significance of published findings.

PMID- 16611462
TI  - False disease region identification from identity-by-descent haplotype sharing in
      the presence of phenocopies.
AB  - Linkage analysis (either parametric or nonparametric) is commonly applied to
      identify chromosomal regions using related individuals affected by disease. In
      complex disease the incomplete relationship between phenotype and genotype can be
      modeled using a phenocopy parameter, the probability that an individual is
      affected given they do not carry the disease mutation of interest, and a
      nonpenetrance parameter, the probability that an individual is not affected given
      they do carry the disease mutation of interest. If the linkage phase between
      multiple markers and a putative disease locus is known, then haplotypes carrying
      the mutation can, in principle, be identified by comparing the chromosome
      segments that are shared identical-by-descent (IBD) across affected individuals.
      We consider here the effect of a nonzero phenocopy rate on the linkage peak and
      hence upon the identification of disease haplotypes that are shared IBD between
      affected individuals. We show, by theory and computer simulation, that in
      diseases for which there is a nonzero phenocopy rate, the chromosomal regions
      identified may not include the true disease locus. We utilize a LOD-1 confidence
      interval for a widely used nonparametric linkage statistic. We find that in
      small/moderate samples this confidence interval may be inappropriate. We give
      specific examples where the phenocopy rates are nonnegligible in some complex
      diseases. The success of further work to identify the causal mutations underlying
      the linkage peaks in these diseases will depend on researchers allowing for the
      presence of phenocopies by examining appropriately wide regions around the
      initial positive linkage finding.

PMID- 16611463
TI  - Heritability of an age-dependent categorical phenotype: cognitive dysfunction.
AB  - We investigated the extent to which cognitive dysfunction is shaped by genetic or
      environmental influences, and whether these factors differ in women and men. All
      members of the Swedish Twin Registry aged 65 and older were screened by telephone
      using the TELE, a brief cognitive assessment instrument (Gatz et al., 2002), and
      the Blessed Dementia Rating Scale (Blessed et al., 1968) from relatives of those
      who scored poorly on the TELE. Data were available for 4308 pairs where both
      members responded and 5070 pairs where only one member was alive and
      participated. To analyze all available data, we used a raw data method extended
      to ordinal data. As the prevalence of cognitive dysfunction increases with age,
      we incorporated age-adjusted thresholds. The best fitting model from biometric
      analyses indicated 35% of the variation in liability to cognitive dysfunction
      could be explained by heritable influences and the remaining 65% by nonfamilial
      environmental influences. Differences by gender were not significant. As this is
      a normative population including cognitively intact individuals, preclinical
      dementia cases and demented individuals, the relative magnitude of genetic and
      environmental effects is of particular interest in light of high heritabilities
      found for dementias such as Alzheimer's disease. The findings emphasize the
      extent to which research is needed to uncover nonfamilial environmental
      influences on cognitive dysfunction in later life.

PMID- 16611464
TI  - The genetic architecture of neuroticism in 3301 Dutch adolescent twins as a
      function of age and sex: a study from the Dutch twin register.
AB  - The objective of this study was to estimate the magnitude of genetic and
      environmental influences to variation in adolescent neuroticism as a function of
      age and sex. Neuroticism was assessed using the Amsterdamse Biografische
      Vragenlijst (ABV): a self-report personality instrument similar in content to the
      Eysenck Personality Questionnaire. Genetic modeling procedures, including age as
      modifier, were fitted to the total sample of 3301 Dutch adolescent twins aged 12
      to 17 years (mean age 15.5). Significant influences of additive genetic factors
      (.59, 95% confidence intervals [CI] .54-.63) and unshared environmental factors
      (.41, 95% CI .37-.45) were found. Our data did not support a role of shared
      environment. Results showed that different genes may influence variation in
      neuroticism between girls and boys. No interaction was found between the variance
      components and age. Results generally support prior findings in adults and young
      children that neuroticism is influenced principally by additive genetic and
      unique environmental factors. The magnitude of the genetic component appears
      higher in the present sample of adolescents than in most studies of adults. The
      present study suggests that, in adolescence, different genes are expressed in
      boys and girls.

PMID- 16611465
TI  - A twin study of lifetime Generalized Anxiety Disorder (GAD) in older adults:
      genetic and environmental influences shared by neuroticism and GAD.
AB  - The nature of Generalized Anxiety Disorder (GAD) and worry across the lifespan
      remains incompletely understood. We investigated genetic and environmental
      influences on GAD and the proportion of genetic and environmental variation in
      GAD that is shared with neuroticism in older adult twins. Participants included
      1618 monozygotic and 2291 same-sexed dizygotic twin pairs from the Swedish Twin
      Registry aged 55 to 74. Participants provided personality information in 1973 and
      also participated in a telephone screening between 1998 and 2002 that included an
      assessment for lifetime GAD. Univariate biometric models indicated that both GAD
      and neuroticism were moderately heritable (.27 and .47, respectively), while the
      balance of variation reflected environmental factors unique to the individual.
      Bivariate analyses indicated that approximately one third of the genetic
      influences on GAD were in common with genetic influences on neuroticism, while
      individual specific environmental influences were virtually unshared between GAD
      and neuroticism. Analyses of sex effects suggested that men and women differed in
      the frequency of lifetime GAD and level of neuroticism; however, no sex
      differences for genetic and environmental influences for either trait were
      identified.

PMID- 16611466
TI  - Examination of the causes of covariation between conduct disorder symptoms and
      vulnerability to drug dependence.
AB  - Conduct disorder (CD) symptoms and substance dependence commonly co-occur. Both
      phenotypes are highly heritable and a common genetic influence on the covariation
      has been suggested. The aim of this study was to determine the extent to which
      genes and environment contribute to the covariance between CD and drug dependence
      using twins from the Colorado Longitudinal Twin Sample and the Colorado Twin
      Registry. A total of 880 twin pairs (237 monozygotic [MZ] female, 195 MZ male,
      116 dizygotic [DZ] female, 118 DZ male and 214 DZ opposite-sex) aged 13 to 18
      (mean = 15.65) were included in the analysis. CD was assessed by lifetime
      Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American
      Psychiatric Association, 1994) symptom count and a polysubstance dependence
      vulnerability index was developed from responses to the Composite International
      Diagnostic Interview--Substance Abuse Module. A bivariate Cholesky Decomposition
      model was used to partition the cause of variation and covariation of the two
      phenotypes. No sex-limitation was observed in our data, and male and female
      parameter estimates were constrained to be equal. Both CD symptoms and dependence
      vulnerability were significantly heritable, and genes, shared environment and
      nonshared environment all contributed to the covariation between them. Genes
      contributed 35% of the phenotypic covariance, shared environment contributed 46%,
      and nonshared environmental influences contributed the remaining 19% to the
      phenotypic covariance. Therefore, there appears to be pleiotropic genetic
      influence on CD symptoms and dependence vulnerability.

PMID- 16611467
TI  - Handedness in twins: joint analysis of data from 35 samples.
AB  - Simultaneous analysis of handedness data from 35 samples of twins (with a
      combined sample size of 21,127 twin pairs) found a small but significant additive
      genetic effect accounting for 25.47% of the variance (95% confidence interval
      [CI] 15.69-29.51%). No common environmental influences were detected (C = 0.00;
      95% CI 0.00-7.67%), with the majority of the variance, 74.53%, explained by
      factors unique to the individual (95% CI 70.49-78.67%). No significant
      heterogeneity was observed within studies that used similar methods to assess
      handedness, or across studies that used different methods. At an individual level
      the majority of studies had insufficient power to reject a purely unique
      environmental model due to insufficient power to detect familial aggregation.
      This lack of power is seldom mentioned within studies, and has contributed to the
      misconception that twin studies of handedness are not informative.

PMID- 16611468
TI  - Migraine with aura and migraine without aura are not distinct entities: further
      evidence from a large Dutch population study.
AB  - It is often debated whether migraine with aura (MA) and migraine without aura
      (MO) are etiologically distinct disorders. A previous study using latent class
      analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO
      and MA. The aim of the present study was to replicate these results in a
      population of Dutch twins and their parents, siblings and partners (N = 10,144).
      Latent class analysis of International Headache Society (IHS)-based migraine
      symptoms resulted in the identification of 4 classes: a class of unaffected
      subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately
      severe type of migraine (class 2), typically without neurological symptoms or
      aura (8% reporting aura symptoms), and a severe type of migraine (class 3),
      typically with neurological symptoms, and aura symptoms in approximately half of
      the cases. Given the overlap of neurological symptoms and nonmutual exclusivity
      of aura symptoms, these results do not support the MO and MA subtypes as being
      etiologically distinct. The heritability in female twins of migraine based on LCA
      classification was estimated at .50 (95% confidence intervals [CI] .27 - .59),
      similar to IHS-based migraine diagnosis (h2 = .49, 95% CI .19-.57). However,
      using a dichotomous classification (affected-unaffected) decreased heritability
      for the IHS-based classification (h2 = .33, 95% CI .00-.60), but not the LCA
      based classification (h2 = .51, 95% CI .23-.61). Importantly, use of the LCA
      based classification increased the number of subjects classified as affected. The
      heritability of the screening question was similar to more detailed LCA and IHS
      classifications, suggesting that the screening procedure is an important
      determining factor in genetic studies of migraine.

PMID- 16611469
TI  - Genetic architecture of smoking behavior: a study of Finnish adult twins.
AB  - Both genetic and environmental factors affect smoking initiation and maintenance,
      but less is known about the genetic architecture of various other smoking-related
      behaviors. The aim of this study is to examine the genetic architecture of
      smoking behavior in a large twin cohort. Questionnaires with an extensive smoking
      history section were mailed to same-sex adult twins of the Finnish twin cohort.
      The final study population included 2923 monozygotic and 6018 dizygotic twin
      pairs aged 24 to 88 years. Two-stage bivariate genetic modeling of age at
      initiation with amount smoked (less than 20 cigarettes per day vs. 20 or more)
      and age at initiation with smoking cessation was done by using the Mx statistical
      package. For men the heritability estimate for age at initiation was .59 (95%
      confidence interval [CI] .49-.69), for amount smoked .54 (95% CI .45-.62) and for
      smoking cessation .58 (95% CI .50-.65). For women the heritability estimates were
      .36 (95% CI .28-.43), .61 (95% CI .46-.70) and .50 (95% CI .39-.60),
      respectively. The genetic correlations between age at initiation and amount
      smoked or smoking cessation were at most .22 in magnitude, indicating that
      genetic influences in age at initiation accounted for at most about 4% of the
      genetic factors in amount smoked or in cessation. Genetic factors are important
      in amount smoked and smoking cessation and they are largely independent of
      genetic influences on age at initiation. This has implications for defining
      phenotypes in searches for genes underlying smoking behaviors.

PMID- 16611470
TI  - Hypotheses on the effect of cadmium on glutathione content of red blood
      corpuscles.
AB  - Previous studies have shown that Glutathione, a tripeptide found in blood, is
      involved in protecting against toxins. Glutathione levels are known to drop in
      response to cadmium. Using 15 twin pairs, we modeled the effect of cadmium on
      glutathione levels. The heritability of glutathione content was 91%. The
      application of cadmium significantly reduced the mean level of GSH. However, this
      reduction in GSH was not due to additive genetic influences in our sample.

PMID- 16611471
TI  - Angiotensinogen G(-6)A polymorphism is associated with the elevation of blood
      pressure in the hypertensive disorders of pregnancy.
AB  - The objective of the present study was to determine whether angiotensinogen G(
      6)A polymorphism is associated with the elevation of blood pressure (BP) in the
      hypertensive disorders of pregnancy in Korean population. The subjects included
      201 cases with the hypertensive disorders of pregnancy and 160 healthy controls.
      The medical records of subjects were reviewed. Cases were classified into the
      four subtypes (transient hypertension, preeclampsia, chronic hypertension, and
      preeclampsia superimposed on chronic hypertension) by the diagnostic criteria
      suggested by the National High Blood Pressure Education Program Working Group.
      Cases were also divided into the high and low BP group by the elevation of BP
      (diastolic BP greater than or equal to 110 mmHg). Maternal angiotensinogen G(-6)A
      polymorphism was determined by restriction fragment length polymorphism.
      Frequencies of AA genotype were significantly higher in the high than in the low
      BP group in the preeclampsia, superimposed preeclampsia, and the combined group
      (N = 201), suggesting that the angiotensinogen G(-6)A allele was significantly
      associated with the elevation of BP in the hypertensive disorders of pregnancy
      among South Korean women. The present findings imply that the elevation of BP can
      serve as an endophenotype for a spectrum of hypertensive conditions in pregnancy.

PMID- 16611472
TI  - Perinatal and early childhood outcomes of twins versus triplets.
AB  - The purpose of this prospective cohort study of twins and triplets was to
      evaluate perinatal and early childhood outcomes through 18 months of age. The
      study population included 141 twin pregnancies (282 twin children) and 8 triplet
      pregnancies (24 triplet children) recruited between May, 1996 and June, 2001.
      Mothers of triplets versus twins were significantly more likely to have
      infertility treatments, to be overweight or obese before conception, to be
      admitted antenatally, and to deliver by cesarean section. Length of gestation for
      triplets was significantly shorter (-2.31 weeks, p < .0001), and more likely to
      be less than 35 weeks (Adjusted Odds Ratio [AOR] 9.38, 95% confidence interval
      [CI] 3.22-27.29). Average birthweight for triplets was significantly lighter (
      495 grams, p < .0001), and more likely to be low birthweight (AOR 11.38, 95% CI
      3.11-41.61). Triplets were also more likely to be admitted to neonatal intensive
      care (AOR 7.97, 95% CI 2.13-29.77), to require mechanical ventilation (AOR 5.67,
      95% CI 2.05-15.65), to develop respiratory distress syndrome (AOR 12.50, 95% CI
      3.89-40.20), or a major morbidity (retinopathy of prematurity, necrotizing
      enterocolitis, ventilator support, or grade III or IV intraventricular
      hemorrhage, AOR 5.67, 95% CI 2.05-15.65). Weight, length, and head circumference
      was significantly smaller at birth for triplets compared to twins, and these
      differences remained through 18 months of age, along with lower mental
      developmental scores at the oldest age. Compared to twins, triplets have greater
      neonatal morbidity, and through 18 months of age lower mental and motor scores,
      slower postnatal growth and more residual stunting, particularly of length and
      head circumference.

PMID- 16611473
TI  - Compromised or competent: analyzing twin children's social worlds.

PMID- 16611474
TI  - Social development of twins.
AB  - This project sought to examine 2 competing hypotheses: first, that twins are
      likely to be more prosocial by virtue of growing up with another same-age peer in
      the home, or second, that they are less prosocial because they have become more
      comfortable interacting with a same-age peer who is both genetically and
      environmentally similar to themselves and therefore they are less comfortable
      with other children who are dissimilar. Two studies were conducted to compare
      twins to singletons on measures of prosocial and aggressive behaviors. In Study
      1, 5-year-olds (N = 91 twins and N = 152 singletons) engaged in a peer play
      situation with an unfamiliar, same-age, same-sex peer, and they were rated on
      items assessing prosocial and aggressive behaviors. Results showed that twins
      were less prosocial but not more aggressive than were singletons. In Study 2,
      which was a supplemented follow-up study of twins in Study 1, 10- to 15-year-old
      twins (N = 98) and singletons (N = 84) were rated by their parents on prosocial
      and aggressive behaviors. No significant differences were found between the
      groups on prosocial behavior, but twins were rated as more aggressive than
      singletons. Thus, in early childhood twins appear to exhibit fewer prosocial
      behaviors with unfamiliar peers, but this prosocial deficit was not aligned with
      parent-reported prosocial behaviors in adolescence. In adolescence, twins were
      rated by parents as more aggressive. These studies suggest that twins may be at
      risk for poorer social interactions in early and middle childhood.

PMID- 16611475
TI  - Compatibility and conflict: negotiation of relationships by dizygotic same-sex
      twin girls.
AB  - This article conceptualizes the child as having active agency in the
      constructions of their social worlds, and reports on a study that understands the
      twin experiences from the perspectives of the twins. It examines how twins
      account for their relationships with their co-twins. The study drew on accounts
      of 60 twin children--10 monozygotic (MZ), 10 dizygotic (DZ) same-sex, 10 DZ
      opposite-sex pairs--aged 5 to 10 years and their parent (n = 30). The children
      engaged in a sticker activity in which they represented their friendships,
      including their friendship with their co-twin. Using the task as a resource, the
      children were asked about their friends, the attributes of friendship and
      examples of everyday friendships encounters. These were audio-recorded and
      transcribed. Further, parents completed a questionnaire that provided demographic
      information and asked parents about the children's social experiences including
      twin children's time spent together, shared interests and their co-twin
      relationship. Using data from the pictorial representation from the sticker task
      and parent questionnaires, differences in relationship between MZ, DZ same-sex
      and DZ opposite-sex twins were examined and used to select a smaller sample for
      detailed study. DZ same-sex twins tended to view their co-twin less favorably and
      there was a nonsignificant trend in which conflict was elevated, compared to the
      other two groups. Based on these findings, the transcripts selected for analysis
      focuses on the DZ same-sex girls. The girls reported that they had differences of
      thought, activity and self-presentation. Conflict, competition and challenge as
      types of social interaction were described, suggesting that the everyday
      relationship of the twin with her co-twin is always being negotiated and
      realigned. Evident here is the complexity of social interactions in which the
      twins engaged everyday with each other.

PMID- 16611476
TI  - Genetic similarity shared by best friends among adolescents.
AB  - Two observations suggest a genetic similarity among close friends: (1) the
      observed similarity among friends in certain traits and behaviors; (2) the
      evidence that many of these traits and behaviors have a genetic component. This
      hypothesis is tested using monozygotic (MZ) twins, dizygotic (DZ) twins, full
      biological siblings, and their best friends from the National Longitudinal Study
      of Adolescent Health (Add Health). Whether the resemblance between MZ twins'
      friends is larger than that between friends of DZ twins and full siblings is
      investigated with respect to 4 individual traits or behaviors: grade point
      average (GPA), AHPVT (the version Peabody Picture Vocabulary Test [PPVT] designed
      for Add Health), aggressive behavior, and depression. Our hypothesis is supported
      in analyses among same-sex friends (not among different-sex friends) for GPA,
      aggressive behavior, and AHPVT.

PMID- 16611477
TI  - Genetic analyses of teacher ratings of problem behavior in 5-year-old twins.
AB  - Behavioral problems in young children can be assessed by asking their parents or
      teachers to rate their behaviors. Genetic analyses of parental ratings show
      relatively large heritabilities for emotional and behavioral problems in young
      children, but data from teachers for this age group are scarce. Sources of
      variation in the Teacher's Report Form (TRF) problem scales were examined. The
      TRF was completed for 211 Dutch 5-year-old twin pairs and 4 single twins. Twins
      rated by different teachers had higher means and variances than twins rated by
      the same teacher, in addition twin correlations were lower in this group. In both
      groups monozygotic (MZ) correlations were generally higher than dizygotic (DZ)
      correlations. A model for twin resemblance was tested that allowed for these
      effects. For 5 problem scales (Withdrawn, Social Problems, Aggressive Behavior,
      Rule Breaking Behavior and Attention Problems) a model with genetic and unique
      environmental sources of variation fitted best to the data. For 3 problem scales
      (Anxious/Depressed, Thought Problems and Somatic Complaints) there were familial
      influences but it was not possible to distinguish between common environmental
      influences or genetic influences. Heritability was 63% for Attention problems,
      around 45% for Withdrawn, Social Problems, Aggressive Behavior and Rule Breaking
      Behavior, and around 30% for Anxious/Depressed, Thought Problems and Somatic
      Complaints.

PMID- 16611478
TI  - Being opposite: is there advantage for social competence and friendships in being
      an opposite-sex twin?
AB  - A recent large-scale study of Finnish adolescent twins (Pulkkinen et al., 2003)
      reported that individuals from opposite-sex twin pairs were more socially
      adaptive than individuals from same-sex pairs or singletons. This finding raised
      questions about the social learning effects of being an opposite-sex twin. The
      current article predicted on the basis of this finding, and evidence from
      singleton populations, that having an opposite-sex twin would yield social
      advantage. It sought to examine the social competencies of opposite-sex twins and
      compare them with same-sex twins and singletons. The study focused on the
      preschool years (age 3 to 6), a period in which the majority of children
      encounter their first large group, nonfamilial social experiences. The study
      obtained reports from parents and teachers of children aged 3 to 6 years: 72
      children (36 pairs) who were dizygotic opposite-sex twins (DZOS), 50 children (25
      pairs) who were dizygotic same-sex twins (DZSS), and 85 singletons of the same
      age and sex as the twins, who had at least one sibling. Reports were made using
      standardized measures of social competencies, behavior problems, language
      development and friendships. The main effects found were of differences in social
      competency between twins and singletons. Twins had lower social competency
      scores. No differences between same-sex and opposite-sex twins were found. The
      findings did not support the hypothesis of social advantage for opposite-sex
      twins in early childhood.

PMID- 16611479
TI  - 'It's good to be different': parent and child negotiations of 'twin' identity.
AB  - Research on twins has tended to focus around the question of
      heredity/environment. As part of this, attention has been paid to how twins'
      family environments impact upon them. By examining twinship as a social identity,
      this article considers the social experience of twinship as it is framed by
      parent-child relations and also actively shaped by twins themselves. Sameness
      constitutes one central defining component of 'twin' identity within Western
      societies. In preparing their twins' bodies for public presentation, parents play
      a key role in communicating twin identity on their children's behalf. However,
      children also construct and convey their own identities through presenting their
      bodies in certain ways. Drawing on findings from a small-scale qualitative study
      of twinship, this article examines how twin identity is created, modified and
      reproduced by parents and child twins. It highlights the active role that twins
      take in constructing their own identities and in shaping the 'twin situation'.

PMID- 16611480
TI  - Having a co-twin with attention-deficit hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common childhood disorder
      which occurs more often in twins than singletons. This article focuses on the
      psychosocial consequences of having a co-twin with ADHD. Specifically, the level
      of anxiety (generalized and separation) in non-ADHD children who have a co-twin
      with ADHD is examined using data from the Australian Twin ADHD Project (ATAP).
      Parental report data on 501 dizygotic (DZ) twin pairs aged 6 to 15 and their
      siblings were used to examine (i) anxiety symptoms in twin pairs discordant for
      ADHD, (ii) how the effects of an ADHD twin on their co-twin and siblings are
      related to the type of ADHD, and (iii) whether the effects are greater for the
      nonaffected twin than nontwin siblings. Results show that anxiety was high in co
      twins of children with the combined subtype of ADHD, with increased symptoms of
      both generalized and separation anxiety. Inattentive ADHD had smaller effects,
      which were confined to generalized anxiety and were specific to the co-twin
      rather than other siblings. These results have clinical implications in managing
      the entire multiple birth family where one twin has ADHD, and also has
      implications for genetic analysis in modeling the relationship of ADHD to
      internalizing disorders.

PMID- 16611481
TI  - Twins and their friendships: differences between monozygotic, dizygotic same-sex
      and dizygotic mixed-sex pairs.
AB  - This study examined the influence of twin status (monozygotic [MZ], dizygotic
      same-sex [DZss] and dizygotic opposite-sex [DZos]) on friendship patterns. It
      examined the friendships of 60 children from 30 twin pairs, mean age 8 years, 4
      months. The study sought to establish how number of friendships and degree to
      which these are shared vary according to twin status. Additionally, it sought to
      assess the children's meaning of shared friendship and to examine whether there
      were group differences according to twin status. Results indicated that, while
      number of friends did not vary, the degree to which friendships were shared was
      significantly associated with twin status. MZ children shared approximately 50%
      of their friends, DZss 25% and DZos 5%. Group patterns emerged from interviews
      with the children concerning shared friendships. MZ twins were characteristically
      positive or accepting about shared friends; DZos pairs shared fewer friends and
      were, therefore, less challenged by the twin situation in negotiating
      friendships; and DZss pairs were more diverse in their reaction with some
      expressing ambivalent or negative views about the twin situation and sharing of
      friendship. The results are presented in the light of their implications for twin
      children's developmental and scholastic progress.

PMID- 16611482
TI  - Relationship between parents' report rate of twin language and factors related to
      linguistic development: older sibling, nonverbal play and preschool attendance.
AB  - The definition and nature of twin language has been a focus of recent studies
      concerned with the phenomenon. There has been a call for a tighter definition and
      understanding of the meaning of twin language (Thorpe et al., 2001). This article
      sought to identify social factors associated with the parent report of twin
      language and thus provide further understanding of the phenomenon. Data from 583
      mothers of twins aged 25 to 59 months were analyzed using multiple logistic
      regression. Factors included in the modeling of parent-report twin language
      included social experience factors such as presence of siblings, attendance at
      preschool education and reports of nonverbal play. It was found that twin pairs
      who didn't have an older sibling, who showed frequent nonverbal play and who
      didn't attend preschool were more likely to have a twin language. Moreover, in
      the group not having an older sibling, the influence of whether twins attended
      preschool or not was strong and the odds ratio was 0.589 (95% confidence
      intervals 0.360-0.963). The findings suggest that social experience factors are
      important predictors of the parent reporting of twin language.

PMID- 16611483
TI  - Twinsburg, Ohio; Twinsburg Research Institute; Twin study summaries; The outside
      world.

PMID- 16611486
TI  - Bias in variance components due to nonresponse in twin studies.
AB  - Incomplete data on trait values may bias estimates of genetic and environmental
      variance components obtained from twin analyses. If the nonresponse mechanism is
      'ignorable' then methods such as full information maximum likelihood estimation
      will produce consistent variance component estimates. If, however, nonresponse is
      'nonignorable', then the situation is more complicated. We demonstrate that a
      within-pair correlation of nonresponse, possibly different for monozygotic (MZ)
      and dizygotic (DZ) twins, may well be compatible with 'ignorability'. By means of
      Monte Carlo simulation, we assess the potential bias in variance component
      estimates for different types of nonresponse mechanisms. The simulation results
      guide the interpretation of analyses of data on perceptual speed from the Swedish
      Adoption/Twin Study of Aging. The results suggest that the dramatic decrease in
      genetic influences on perceptual speed observed after 13 years of follow-up is
      not attributable solely to dropout from the study, and thus support the
      hypothesis that genetic influences on some cognitive abilities decrease with age
      in late life.

PMID- 16611487
TI  - On the probability of dizygotic twins being concordant for two alleles at
      multiple polymorphic loci.
AB  - Accurate determination of same-sex twin zygosity is important for medical,
      scientific and personal reasons. Determination may be based upon questionnaire
      data, blood group, enzyme isoforms and fetal membrane examination, but assignment
      of zygosity must ultimately be confirmed by genotypic data. Here methods are
      reviewed for calculating average probabilities of correctly concluding a twin
      pair is monozygotic, given they share the same genotypes across all loci for
      commonly utilized multiplex short tandem repeat (STR) kits. Numerous tools
      enabling convenient and accurate zygosity probability calculation may be accessed
      via the ZygProb homepage at http://genepi.qimr.edu.au/general/daleN/ZygProb/

PMID- 16611488
TI  - Sex differences in heritability of neck pain.
AB  - Experimental studies have suggested biological factors as a possible explanation
      for gender disparities in perception of pain. Recently, heritability of liability
      to neck pain (NP) has been found to be statistically significantly larger in
      women compared to men. However, no studies have been conducted to determine
      whether the sex differences in heritability of NP are due to sex-specific genetic
      factors. Data on lifetime prevalence of NP from a population-based cross
      sectional survey of 33,794 Danish twins were collected and age-stratified
      univariate biometrical modeling using sex-limitation models was performed based
      on 10,605 dizygotic (DZ) twins of opposite sex to estimate the qualitative sex
      differences. In a full sex-limitation model the genetic component in females were
      higher than in males, but the genetic and the shared environmental correlations
      were equal to what is normally assumed between same-sex DZ twins. A 'no-sex
      effects' model showed the overall best model fit which confirms absence of sex
      related gene interaction. The age-stratified sex-limitation models showed similar
      results. Thus, there is no evidence for a sex-specific genetic influence in the
      liability of heritability of NP.

PMID- 16611489
TI  - Heritability and stability of resting blood pressure in Australian twins.
AB  - In Australian twins participating in three different studies (1979-1996), the
      contribution of genetic and environmental influences to variation in resting
      systolic (SBP) and diastolic blood pressure (DBP) was studied. The sample
      consisted of 368 monozygotic and 335 dizygotic twin pairs with measurements for
      both individuals. Blood pressure measurements in two studies were available for
      115 complete twin pairs, and 49 twin pairs had measurements in three studies.
      This allowed assessment of blood pressure tracking over an average period of 12
      years in the age range of 23 to 45 years. Multivariate analyses showed
      significant heritability (h2) of blood pressure in all studies (SBP h2 = 19%-56%,
      DBP h2 = 37%-52%). In addition, the analyses showed that the blood pressure
      tracking was explained by the same set of genetic factors. These results
      replicate an earlier finding in Dutch twins that also showed stability of the
      contribution of genetic factors to blood pressure tracking.

PMID- 16611490
TI  - A twin study of nitric oxide levels measured by serum nitrite/nitrate.
AB  - Nitrite and nitrate are the stable end products of the L-arginine-NO pathway, and
      the sum of nitrite and nitrate (NOx) is a common way to measure nitric oxide (NO)
      production or secretion. To uncover any genetic influence on NO, we measured NOx
      in serum samples from monozygotic twin pairs after an overnight fast.
      Heritability was estimated as intraclass correlation coefficient. We arrived at a
      heritability estimate of .32 (95% confidence interval 0.17-0.45) for NOx. The
      numerical heritability estimate was higher for females than for males (0.38 vs.
      0.21), and higher for nonsmokers than for smokers (0.36 vs. 0.22). The
      heritability estimate of NOx was lower than the heritability estimate for other
      cardiovascular risk factors. This study suggests a low degree of heredity for NOx
      levels.

PMID- 16611491
TI  - Heritability of the second to fourth digit ratio (2d:4d): A twin study.
AB  - The second to fourth finger length ratio (2d:4d) has been the subject of much
      recent work and is thought to be related to diverse gender and hormone-related
      traits including sports ability, disease susceptibility, attractiveness and
      sexuality. It is established in utero and remains constant in adulthood. Familial
      clustering has been thought to contribute to the development of 2d:4d from early
      studies but no twin studies exploring heritability have been reported to date. In
      this study, a sample of 456 female twin pairs (148 monozygotic [MZ], 308
      dizygotic [DZ]) aged 18 to 79 years was used to estimate the heritability of
      2d:4d for the right and left hands. Finger lengths were derived from hand x-rays.
      Variance components analysis was used to estimate and contrast genetic and
      environmental effects on this phenotype. The mean 2d:4d was 0.92 (SD = 0.001) for
      both hands. The MZ intraclass correlation was higher than in DZ (.66 vs. .35 for
      right 2d:4d, and .71 vs. .37 for left 2d:4d). The best fit model included
      additive polygenic and unique environmental effects ('AE' model), with no
      significant common environmental effects detected. Heritability was estimated to
      be approximately 66% for 2d:4d (95% confidence interval 0.5-0.78). These results
      suggest a substantial genetic contribution to the determination of this
      hormonally related skeletal ratio in women, which could be more influential than
      the effects of common prenatal environmental factors. However the current study
      design does not preclude the possibility of confounding between heritability
      estimates and unobserved prenatal effects.

PMID- 16611492
TI  - Efficacy of retrospective recall of attention-deficit hyperactivity disorder
      symptoms: A twin study.
AB  - Attention-deficit hyperactivity disorder (ADHD) is currently recognized as a
      neurobiological, genetically based disorder in both children and adults. In this
      article we examine whether, by using a sample of middle-aged male twin veterans,
      the phenotypic characterization, prevalence, heritability and the longitudinal
      course of the illness is comparable to results observed in samples of children
      and adolescents. We evaluated the utility of adult reports of lifetime ADHD
      symptoms by examining the heritability of retrospectively reported childhood
      symptoms, using both symptom-based and discrete classification-based approaches,
      as well as examining the persistence of ADHD symptoms into adulthood for that
      subsample of individuals who were judged to possibly have ADHD as children. Our
      results showed prevalence rates that were approximately similar to those observed
      in other studies, demonstrable familiality, similar item endorsement patterns, a
      strong genetic association between hyperactive and inattentive subtypes, and a
      longitudinal decline in symptom severity. We concluded that while assessing ADHD
      in adult probands may be less accurate than with children or adolescents, since
      it demonstrates several characteristics in common with other assessment
      techniques it remains a viable diagnostic and research strategy, even with
      population samples.

PMID- 16611493
TI  - Twins have slightly higher self-concepts than singletons in the elementary school
      period: A study of South Korean twins and singletons.
AB  - The twin method assumes that the trait under study is similar in twins and
      singletons so that the results from twin samples can be generalized to the
      singleton population. The purpose of the present study was to compare self
      concept in twins and singletons matched in parental level of education. The 6
      cluster scales of the Piers-Harris Children's Self-Concept Scale (P-H) were
      administered to 630 singleton children and 635 twins aged 7 to 12 years. Model
      fitting analyses yielded two conclusions. First, self-concept was generally
      similar between first- and second-born twins and between monozygotic and
      dizygotic twins across the 6 cluster scales of the P-H. Second, twins
      consistently exceeded singletons for all 6 cluster scales of the P-H. However,
      the effect sizes of differences between twins and singletons were small except
      for one scale, Physical Appearance and Attributes.

PMID- 16611494
TI  - How long do the consequences of parental preference last: A study of twins from
      pregnancy to young adulthood.
AB  - We analyzed depressive and psychosomatic symptoms in relation to parental
      preference in 419 twins at the age of 22 to 30 years. Depressiveness was elicited
      with Children's Depression Inventory and reported as a total score and three
      subscales (low self-confidence, anhedonia and sadness) based on factor analysis
      as reported in a previous epidemiological study conducted in Finland. Items
      assessing nervous complaints and somatic symptoms were adapted from Finnish
      studies of juvenile health habits. Twins reported the preference in two
      directions: experienced parental preference towards either twin, and twin's own
      preference towards either parent. About half of the twins were from pairs where
      both twins experienced having been equally close to both parents, while about 30%
      were from 'equal and mother's' pair, where one twin evaluated having been
      preferred by the mother and the co-twin evaluated having been equally close to
      both parents. According to the twins' own preference, about one third of the twin
      pairs were 'both equal', one third 'both mother's' and one third 'equal and
      mother's'. Those male twins who were equally close to both parents (experienced
      parental preference) had least total depressiveness, while females in the
      intermediate situation had the highest self-confidence and least anhedonia and
      nervousness. According to twins' own preference, twins who felt equally close to
      both parents had the least depressiveness and anhedonia. The intermediate
      position seems to be the best alternative, as these twins had the least symptoms.

PMID- 16611495
TI  - Frequency of twin births in developed countries.
AB  - Twinning rates in developed countries have recently registered an increase. At
      the end of the 1970s, the change in mother's age structure has partially
      contributed to the growth in the proportion of multiple births. In fact, the
      evolution of twinning rates is related to the calendar of maternity since,
      comparatively to younger mothers, older women more frequently have twins.
      Moreover, the growing frequency of multiple births also depends on fertility
      treatments, which are largely used in the developed countries. National data from
      the civil birth registration systems are taken into account in order to describe,
      in a comparative study, the main trends of twinning rates in the 20th century.

PMID- 16611496
TI  - Stillbirth rates in singletons, twins and triplets in Sweden, 1869 to 2001.
AB  - The temporal variation in the stillbirth rates (SBR), measured as the number of
      stillborn per 1000 total births, among singletons, twins and triplets was studied
      on Swedish birth data for the period 1869 to 2001 and comparisons with data from
      other populations were made. Among both single and multiple births there were
      marked, almost monotonously decreasing trends in the stillbirth rates. Among
      singletons the stillbirth rate decreased from 29.5 per 1000 in the period 1869 to
      1878 to 3.4 in the period 1991 to 2001. Among twins the stillbirth rate decreased
      from 94 per 1000 in 1869 to 1878 to a minimum of 8.2 in 1991 to 2001 and among
      triplets from 166 per 1000 to a minimum of 19.8. The relative declining pattern
      in the SBRs was almost the same, being 88% among singletons, 91% among twins and
      88% among triplets. In the 1980s and 1990s the definition of the stillbirth rate
      was changed in many countries, including Finland, but no changes in the
      definition of stillbirths have been made in Sweden. The effect of the artificial
      reproduction techniques, including in vitro fertilization, on the rates of
      multiple maternities is also discussed. It was noted especially that they had a
      more marked effect on the triplet than on the twinning rate.

PMID- 16611497
TI  - Determination of zygosity by questionnaire and physical features comparison in
      Chinese adult twins.
AB  - This study reports on the determination of zygosity in Chinese adult twins by
      simple questionnaire and physical features comparison. The subjects were 511 twin
      pairs from two cities and their town areas, consisting of 371 monozygotic (MZ)
      and 140 same-sex dizygotic (DZ) pairs, identified by ABO blood group and
      multiplex polymerase chain reaction of several polymorphic short tandem repeat
      markers. The twins themselves responded to 8 questionnaire items, 4 items on twin
      similarity, and 4 items on the frequency of mistaking one twin for another by
      parents, relatives, teachers and strangers when they were 6 to 13 years old.
      Research assistants responded to 20 items regarding twins' physical features at
      the moment of interview. A parsimonious model established using stepwise logistic
      regression analysis of the 28 items showed that the total accuracy of zygosity
      diagnosis was 90.1%. The accuracy was 89.2% when using only the items dealing
      with the confusion of twins and 85.4% using only similarity. In the
      questionnaire, 'facial appearance', 'mistaken by teachers' and 'mistaken by
      strangers' had stronger discriminating power between MZ and DZ twins. Two
      physical features--'eyelid' and 'middigital hair'--were informative to some
      extent. There was no statistically significant sex and area difference in the
      validity of such questionnaire and physical features comparison-based
      classification. In conclusion, questionnaire-based zygosity assessment in this
      Chinese adult twin sample could still be regarded as a valid and valuable
      classification method. Physical features comparison, however, could only provide
      limited information for zygosity determination.

PMID- 16611498
TI  - Linguistic features of Japanese twins at 3 or 4 years of age evaluated by
      Illinois test of psycholinguistic abilities.
AB  - In general, twins have delayed language development early in childhood compared
      with singletons. The purpose of this study was to clarify the overall linguistic
      features of twins. A Japanese version of the Illinois Test of Psycholinguistic
      Abilities (ITPA) was administered in 24 twin pairs (aged 3 to 4 years) at their
      own homes. The overall language abilities of the twins were in the normal range
      (based on ITPA normative data: mean scale score 36.0 +/- 6.0 points), and for the
      ITPA subtests only, Auditory Reception fell within the range of language disorder
      (mean scale score 24.9 +/- 5.1 points). The findings suggest that in 3- to 4-year
      old Japanese twins, overall language abilities are not delayed. However, there
      may be specific difficulties with auditory reception skills.

PMID- 16611499
TI  - Pregnancy outcome among twins conceived after subfertility treatment compared
      with natural twins: A population-based study.
AB  - Pregnancy outcome and characteristics of women who conceive following
      subfertility treatment remains a subject of great interest. We analyzed these
      variables among 199 women who delivered a registerable twin birth compared with
      1773 women who delivered a naturally conceived twin birth in a population-based
      obstetric cohort drawn from around Oxford, England. Treatment was restricted to
      conceptions involving simple ovulation induction only. Treated mothers were of
      significantly higher social class and older, more likely to deliver girls and to
      be delivered by cesarean section, and significantly less likely to be smokers at
      the time of antenatal booking and to have delivered previous pregnancies.
      Pregnancy outcome was similar between the two groups for most measures, with the
      exception of birthweight which was lower in treated twins, though not
      significantly so. Overall the results are reassuring with respect to outcome in
      twin pregnancies following simple ovulation induction.

PMID- 16611500
TI  - Chorion type, birthweight discordance and tooth-size variability in Australian
      monozygotic twins.
AB  - Chorion type is an important variable that can affect the prenatal environment of
      monozygotic (MZ) twin pairs, leading to differences in growth and development. In
      particular, vascular anastomoses between monochorionic (MC) MZ twin pairs can
      lead to an imbalance in nutrition between co-twins. One objective of this study
      was to determine whether maternal reports, hospital records or birthweight
      discordances found in MZ co-twins provide reliable indications of
      monochorionicity. The other objective was to test the hypotheses that in MZ twin
      pairs of known chorion type, MC twin pairs would show greater birthweight
      differences and greater within-pair variability in permanent tooth size than
      dichorionic (DC) twin pairs, reflecting greater differences in intrauterine
      environment between MC MZ pairs. Birthweights and tooth size data were recorded
      for 170 pairs of MZ Australian twins enrolled in an ongoing study of dentofacial
      growth and development. Chorion type based on maternal reports was compared with
      that based on hospital records for a subsample of 68 pairs of these MZ twins.
      Maternal reports were found to be unreliable for determining chorion type and
      hospital records often did not provide enough information to be certain about
      chorionicity. For 27 twin pairs with confirmed chorion type, associations were
      tested between birthweight discordances in MZ twin pairs and chorion type, and
      also between intrapair variances for tooth size and chorion type. A significant
      association was noted between birthweight discordance and chorion type (p < .05),
      with greater discordances occurring more often in MC twin pairs. Although
      significant heterogeneity of intrapair variances for tooth size was found in only
      5 of 48 comparisons, intrapair variances for crown dimensions were greater
      significantly more often in MC pairs than DC pairs (p < .05). Our findings
      indicated that neither maternal reports nor often hospital records can be relied
      upon for information on chorion type. However, when analyses were performed on
      data for MZ twin pairs of known chorion type, we found evidence of a significant
      association between intrapair birthweight differences and chorion type and also
      between intrapair variances of dental crown measurements and chorion type.
      Consistent with our hypotheses, large birthweight discordances were found to
      occur more often in MC twin pairs than DC twin pairs, and intrapair variances for
      tooth size in MC twin pairs exceeded those in DC twin pairs more often than
      expected due to chance.

PMID- 16611501
TI  - The relationship between birthweight discordance and perinatal mortality of one
      of the twins in a twin pair.
AB  - This study aimed to evaluate the prevalence of birthweight discordance among
      twins, to determine the risk cut-off point for birthweight discordance, and to
      clarify whether perinatal deaths are aggravated by birthweight discordance or by
      low birthweight itself. A population-based analysis of all twins born between
      1995 and 1999 in Japan was conducted using data collected from national birth,
      death and stillbirth certificates. Birthweight discordance was determined as:
      higher birthweight minus lower birthweight divided by higher birthweight
      multiplied by 100. Among twins with a birthweight discordance of more than 15%,
      the fetal and perinatal mortality rate was higher than that of twins with a
      discordance of less than 15%. Ninety per cent of the relative cumulative
      frequency of twin live-births were within 25% of the birthweight discordance.
      Logistic regression analysis showed that the stillbirth of at least one of the
      twins is associated with the birthweight of the larger twin and birthweight
      discordance. It also showed that the stillbirth of both twins in the twin pair is
      associated with the birth-weight of larger twins and the gestational weeks. It
      was clarified that birthweight discordance was associated with the stillbirth of
      only one twin in the twin pair, and the stillbirth of both twins in the twin pair
      was associated with low birthweight itself.

PMID- 16611502
TI  - Breastfeeding rates among singletons, twins and triplets in Japan: A population
      based study.
AB  - This study was performed to determine the rates of breastfeeding among
      singletons, twins and triplets in Japan, and identify factors associated with the
      decision to breastfeed or bottle-feed. We analyzed a database of medical check-up
      of infants aged 3 to 6 months between April 2001 and July 2004 in Nishinomiya
      City in Japan. This medical check-up is given to almost 100% of infants in Japan
      and the data of 15,262 infants were analyzed. Among these, 14,963 (98.0%) were
      singletons, 290 (1.9%) were twins and 9 (0.1%) were triplets. Exclusive breast
      feeding was chosen by 6680 (43.8%) mothers, mixed-feeding by 4645 (30.4%)
      mothers, and bottle-feeding with formula milk only by 3900 (25.6%) mothers. The
      rate of exclusive breastfeeding among twins or triplets was significantly lower
      than among singleton babies: 4.1% among twins or triplets, and 44.7% among
      singletons. Moreover, twins and triplets were independently associated with a
      higher rate of bottle-feeding: the odds ratio indicated that mothers who had
      twins or triplets were 2.44 times more likely to choose bottle-feeding with
      formula milk only than those who had singletons. Sucking ability at birth was
      associated with a higher rate of bottle-feeding: the odds ratio indicated that
      mothers who had infants with poor sucking ability at birth were 1.56 times more
      likely to choose bottle-feeding as those who had infants with normal sucking
      ability.

PMID- 16611508
TI  - Responding to intimate partner violence: what role for general practice?

PMID- 16611509
TI  - The quality and outcomes framework of the GMS contract: a quiet evolution for
      2006.

PMID- 16611510
TI  - Guiding principals--general practice and career choices.

PMID- 16611511
TI  - Hazardous drinking and the NHS: the costs of pessimism and the benefits of
      optimism.

PMID- 16611512
TI  - Increased awareness of intimate partner abuse after training: a randomised
      controlled trial.
AB  - BACKGROUND: Intimate partner abuse is very common among female patients in family
      practice. In general, doctors overlook the possibility of partner abuse. AIM: To
      investigate whether awareness of intimate partner abuse, as well as active
      questioning, increase after attending focus group and training, or focus group
      only. DESIGN OF STUDY: Randomised controlled trial in a stratified sample.
      SETTING: Family practices in Rotterdam and surrounding areas. METHOD: A full
      training group (n = 23), a group attending focus group discussions alone (n =
      14), and a control group (n = 17) were formed. Data were collected with incident
      reporting of every female patient (aged >18 years) that was suspected of, or
      presented, partner abuse during a period of 6 months. The primary outcome measure
      was the number of reported patients; the secondary outcome measure was the number
      of patients with whom the GP had non-obvious reasons to suspect/discuss abuse.
      RESULTS: Comparison of the full-training group (n = 87 patients) versus the
      control group (n = 14 patients) resulted in a rate ratio of 4.54 (95% confidence
      interval [CI] = 2.55 to 8.09, P <0.001); the focus group only group (n = 30
      cases) versus control group: rate ratio of 2.2 (95% CI = 1.14 to 4.26, P =
      0.019); full-training versus the focus group only group: rate ratio of 2.19 (95%
      CI = 1.36 to 3.52, P = 0.001). Comparison of the fulltraining group with the
      untrained groups for awareness of partner abuse in case of non-obvious signs
      resulted in: odds ratio 5.92 (95% CI = 2.25 to 15.62, P <0.01) all corrected for
      sex, district, practice setting, working part/full-time, experience, and age of
      the doctor. CONCLUSIONS: Training was the most significant determinant to improve
      awareness and identification of intimate partner abuse. Active questioning
      increased, especially where there were non-obvious signs. The focus group on its
      own doubled the awareness of partner abuse.

PMID- 16611513
TI  - The acceptability of routine inquiry about domestic violence towards women: a
      survey in three healthcare settings.
AB  - BACKGROUND: Domestic violence is frequently only disclosed when healthcare staff
      directly inquire. Healthcare staff worry that inquiry may offend. AIM: To
      identify the characteristics of women who find inquiry about domestic violence by
      healthcare staff unacceptable. DESIGN OF STUDY: Anonymous interview based cross
      sectional study. SETTING: Three general practice surgeries, one antenatal clinic
      and one emergency department in Cambridge, England, with a total of 2306 women
      attending for health care. METHOD: Cross-sectional survey. RESULTS: In total 1452
      completed questionnaires were returned; response rate 63%. One hundred and twenty
      two women (8.4%) indicated that they found inquiry by healthcare staff
      unacceptable. Women at the emergency department and GP surgeries were more likely
      to find inquiry unacceptable (odds ratio [OR] = 3.3, 95% confidence interval [CI]
      = 1.1 to 9.9) and (OR = 3.9, 95% CI = 1.3 to 11.5) respectively, than in the
      antenatal clinic. Women at the antenatal clinic reported lower rates of abuse
      within 1 year than at the emergency department or antenatal clinic. Abuse within
      1 year was strongly associated with finding inquiry unacceptable (OR = 4.5, 95%
      CI = 1.8 to 11.4), but not lifetime abuse (OR = 0.9, 95% CI = 0.5 to 1.9).
      CONCLUSIONS: Inquiry about domestic violence by healthcare staff is acceptable to
      most women. Acceptability is highest in women who have not been abused in the
      last year and who are attending the antenatal clinic. Women who attend the
      antenatal clinic have lower rates of abuse within 1 year.

PMID- 16611514
TI  - CQI-2--a new measure of holistic interpersonal care in primary care
      consultations.
AB  - BACKGROUND: The Consultation Quality Index (CQI) is a holistic quality marker for
      GPs based on patient enablement, continuity of the care and consultation length.
      AIM: To evaluate the CQI-2, a new version of the CQI incorporating a process
      measure of GP empathy (the Consultation and Relational Empathy Measure). DESIGN
      OF STUDY: Cross-sectional questionnaire study. SETTING: General practice in the
      west of Scotland. METHOD: Empathy, enablement, continuity, and consultation
      length were measured in 3044 consultations involving 26 GPs in 26 different
      practices in the west of Scotland. CQI-2 scores were calculated and correlated
      with additional data on GPs' and patients' attitudes. Comparisons were also made
      with the UK-wide data from which the original CQI had been calculated. RESULTS:
      CQI-2 scores were independent of deprivation, access, demographics, and case-mix.
      GPs with lower CQI-2 scores valued empathy and longer consultations less than
      these GPs with higher CQI-2 scores. 'Below average CQI-2' GPs (those in the
      bottom 25%) also felt less valued by patients and colleagues. Patients' showed
      less confidence in and gained less satisfaction from these doctors. Data ranges
      from the study were comparable with the UK data ranges used to construct the
      original CQI. CONCLUSIONS: The CQI-2 is a new measure of holistic interpersonal
      care. In a small but representative sample of GPs it appears to differentiate
      between below and above average doctors. CQI-2 scores may reflect important
      aspects of morale, core values and patient-centred care. There may be potential
      for its use as part of professional development and as a component of the general
      medical services contract.

PMID- 16611516
TI  - Overall quality of outcomes framework scores lower in practices in deprived
      areas.
AB  - BACKGROUND: There has been much debate as to whether quality points allocated
      through the new general medical services contract are more difficult to achieve
      for practices in deprived and rural areas. We used multiple regression to assess
      the relationships between deprivation, rurality and the number of overall quality
      points achieved by each practice. Multiple deprivation was significantly
      inversely related to quality points achieved. Practices in villages and towns
      gained 2% more quality points than urban areas and hamlets.

PMID- 16611515
TI  - A prospective study of the consulting behaviour of older people with knee pain.
AB  - BACKGROUND: Knee pain is common among older adults but only a minority consult
      their doctor about it. AIM: To determine predictors of new episodes of
      consultation in primary care among older people with knee pain. DESIGN OF STUDY:
      Population-based prospective cohort study linking baseline survey to primary care
      medical records. SETTING: Three general practices in North Staffordshire, UK.
      METHOD: Subjects were 1797 people aged > or =50 years who responded to a general
      population survey, reported knee pain in the previous 12 months and had no record
      of a knee disorder consultation in the 18 months prior to the survey. The main
      outcome measure was a record of a knee disorder consultation in the 18 months
      following the survey. RESULTS: The incidence of a new episode of general practice
      care was approximately 10% per year. Apart from chronicity (odds ratio [OR] =
      1.5; 95% confidence interval [CI] = 1.1 to 2.1), measures of pain severity were
      not strong influences on future consultation. No social support (measured by
      having no partner) increased likelihood of future consultation (OR = 1.3; 95% CI
      = 1.0 to 1.8). Among those with chronic and severe pain, main predictors were
      previous experiences of health care (use of non-GP services OR = 1.8; previous
      knee injury OR = 1.7). Current depression reduced likelihood of consulting about
      the knee problem (OR = 0.6; 95% CI = 0.3 to 0.9). CONCLUSIONS: Knee pain is
      common in the older population but a minority consult their doctor about it.
      Severity of pain and disability is not a strong influence on consultation. For
      those more severely affected, depression may act as a barrier to healthcare use.

PMID- 16611517
TI  - Career intentions and preferences of GP registrars in Yorkshire.
AB  - With a shortage of GPs in England, there is a need to consider the career
      development for new GPs to ensure that they remain in post. This study examines,
      by means of a postal questionnaire survey, the views of GP registrars (GPRs)
      about their future careers in Yorkshire, England. The response rate was 59%. One
      hundred and eighteen (60%) responders were female, of whom 80 (39%) were planning
      to work part time. One hundred and fifty-six (76%) GPRs planned to take up a
      specific job in primary care; 81 (40%) in a general practice rather than a
      primary care trust setting. One hundred and seven (52%) had sought a different
      medical career prior to general practice and 113 (55%) did not feel well prepared
      to find a suitable practice. Interest in teaching was expressed by 167 (82%) and
      in sub-specialisation by 170 (83%). One hundred and seventeen (57%) GPRs said
      that their job choice was affected by domestic commitments. More males than
      females intended to become a principal. Primary care trusts should consider the
      profile and aspirations of the workforce and a more structured approach to career
      guidance is required.

PMID- 16611518
TI  - Council tax valuation bands and contacts with a GP out-of-hours service.
AB  - UK GPs are no longer responsible for the organisation of out-of-hours care for
      their patients, but resources remains capitation-based. This cross-sectional
      study tests whether council tax valuation bands can predict the demand for such
      services. All out-of-hours contacts made by patients in North Wiltshire over 4
      months were classified by council tax band; frequencies compared with official
      population statistics. Council tax band predicts out-of-hours GP workload
      irrespective of age and sex: the more modest the home, the higher the GP contact
      rate. It may prove more difficult to sustain out-of-hours services in deprived
      parts of the UK.

PMID- 16611520
TI  - Recognising domestic violence in clinical practice using the diagnoses of
      posttraumatic stress disorder, depression and low self-esteem.
AB  - This discussion paper reviews the health impacts, physical and mental, of
      domestic violence and explores the link between domestic violence and
      psychological symptoms. This paper focuses more on posttraumatic stress disorder
      (PTSD) than depression and low self-esteem because doctors are less familiar with
      PTSD. The barriers preventing health workers from detecting domestic violence are
      reviewed and the fear of health professionals that asking about trauma can harm
      patients is explored. The article then outlines practical strategies to improve
      detection of domestic violence using patients' presenting psychological symptoms
      and the diagnoses frequently associated with domestic violence namely, PTSD,
      depression and low self-esteem. It is argued that it is inadvisable to try to
      implement a policy of screening for domestic violence in general practice when
      the public health model is currently inappropriate. The paper discusses why the
      diagnostic frameworks of depression and PTSD are helpful in general practice, not
      only in detecting domestic violence but in working with the patient to establish
      trust and ways forward that can be tailored to meet the needs of the patient and
      their children. Patients' and professionals' dilemmas about what to do once
      domestic violence is detected are briefly explored.

PMID- 16611519
TI  - How can health services effectively meet the health needs of homeless people?
AB  - BACKGROUND: Homelessness affects many people in contemporary society with
      consequences for individuals and the wider community. Homeless people experience
      poorer levels of general physical and mental health than the general population
      and there is a substantial international evidence base which documents multiple
      morbidity. Despite this, they often have problems in obtaining suitable health
      care. AIM: To critically examine the international literature pertaining to the
      health care of homeless people and discuss the effectiveness of treatment
      interventions. DESIGN OF STUDY: Review and synthesis of current evidence. METHOD:
      Medline (1966-2003), EMBASE (1980-2003), PsycINFO (1985-2003), CINAHL (1982
      2003), Web of Science (1981-2003) and the Cochrane Library (Evidence Based
      Health) databases were reviewed using key terms relating to homelessness,
      intervention studies, drug misuse, alcohol misuse and mental health. The review
      was not limited to publications in English. It included searching the internet
      using key terms, and grey literature was also accessed through discussion with
      experts. RESULTS: Internationally, there are differing models and services aimed
      at providing health care for homeless people. Effective interventions for drug
      dependence include adequate oral opiate maintenance therapy, hepatitis A, B and
      tetanus immunisation, safer injecting advice and access to needle exchange
      programmes. There is emerging evidence for the effectiveness of supervised
      injecting rooms for homeless injecting drug users and for the peer distribution
      of take home naloxone in reducing drug-related deaths. There is some evidence
      that assertive outreach programmes for those with mental ill health, supportive
      programmes to aid those with motivation to address alcohol dependence and
      informal programmes to promote sexual health can lead to lasting health gain.
      CONCLUSIONS: As multiple morbidity is common among homeless people, accessible
      and available primary health care is a pre-requisite for effective health
      interventions. This requires addressing barriers to provision and multi-agency
      working so that homeless people can access the full range of health and social
      care services. There are examples of best practice in the treatment and retention
      of homeless people in health and social care and such models can inform future
      provision.

PMID- 16611521
TI  - Prescribing to substance misusers. Letter response.

PMID- 16611522
TI  - Plastic fantastic.

PMID- 16611523
TI  - A clear response.

PMID- 16611524
TI  - Single-handed or group practice, quality of care and patient satisfaction.

PMID- 16611525
TI  - Vitamin D supplementation needs consistent and planned approach.

PMID- 16611526
TI  - The white paper: contest for contracts.

PMID- 16611527
TI  - Topical steroid and antibiotic combination therapy in red eye conditions.

PMID- 16611530
TI  - Big pharma--paper tiger.

PMID- 16611529
TI  - Access to health care for people seeking asylum in the UK.

PMID- 16611535
TI  - [Respiratory infection caused by Chlamydia pneumoniae].
AB  - INTRODUCTION: Chlamydia pneumoniae is a pathogen usually associated with
      respiratory pathology. It has been estimated that this agent causes 5 to 15% of
      all pneumonias but its incidence among hospitalised children with respiratory
      infections is unknown. OBJECTIVE: Characterization of the Chlamydia pneumoniae
      respiratory infections in hospitalised children. PATIENTS AND METHODS:
      Retrospective longitudinal study of the Chlamydia pneumoniae respiratory
      infections in children admitted between January 1999 and June 2001 in the
      Department of Pediatrics in the Fernando Fonseca Hospital-Portugal. Sex, age,
      race, socio-economic status, number of scholar siblings, frequency of
      nursery/school, parents smoking habits, familiar atopy, personal history,
      clinical presentation, diagnosis, treatment and follow-up were analysed for each
      child. RESULTS: 55 cases were documented, 60% males and 73% whites. The age on
      admission varied between 17 days and 14 years-old, with a higher incidence below
      5 years-old (60%). Twenty-three (42%) of the children were in nursery or in
      school and 12 (44%) had siblings at school-ages. Parent smoking habits were
      documented in 21 (38%) and familiar atopy in 21 (38%) children. Respiratory atopy
      (6 children), gastroesophageal reflux (3), cerebral palsy (1), cleft palate (1)
      and prematurity (1). Pneumonia was the most frequent clinical presentation (63%),
      followed by bronchiolitis (20%). The clinical presentation was not specific, with
      cough (84%), respiratory distress (65%) and fever (58%) being the most frequent
      signs. The most prevalent radiological pattern was the interstitial (42%).
      Coinfection by other agents occurred in five cases: S. pneumoniae (2), H.
      influenzae tipo b (1), P. aeruginosa (1) and tuberculosis (1). Complications were
      documented in 32 (58%) children: hypoxemia (20), pleural effusion (8),
      atelectasis (2) e atelectasis and hypoxemia (2). Macrolides were prescribed in
      44% cases. DISCUSSION: This study calls the attention to the fact that Chlamydia
      pneumoniae infection is an etiology to be considered in children with respiratory
      infection and hospitalisation criteria. This infection can occur in all ages.
      Because the clinical presentation is not specific and complications can occur, a
      high level of suspicion is necessary for its diagnosis.

PMID- 16611536
TI  - Intracellular Ca2+ concentration in the N1E-115 neuronal cell line and its use
      for peripheric nerve regeneration.
AB  - Entubulation repair of peripheral nerve injuries has a lengthy history. Several
      experimental and clinical studies have explored the effectiveness of many
      biodegradable and non-degradable tubes with or without addition of molecules and
      cells. The main objective of the present study was to develop an economical and
      also an easy way for culturing a neural cell line which is capable of growing,
      differentiating and producing locally nerve growth factors, that are otherwise
      extremely expensive, inside 90 PLA/10 PLG nerve guides. For this purpose the
      authors have chosen the N1E-115 cell line, a clone of cells derived from mouse
      neuroblastoma C-1300 with the perspective of using this differentiated cellular
      system to cover the inside of 90 PLA/10 PLG nerve guides placed to bridge a nerve
      gap of 10 mm in the rat sciatic nerve experimental model. The N1E-115 cells
      proliferate in normal culture medium but undergo neuronal differentiation in
      response to DMSO. Upon induction of differentiation, proliferation of N1E-115
      cells ceases, extensive neurite outgrowth is observed and the membranes become
      highly excitable. While it is known that Ca2+ serves as an important
      intracellular signal for cellular various processes, such as growth and
      differentiation, be toxic to cells and be involved in the triggering of events
      leading to excitotoxic cell death in neurons. The [Ca2+]i in non-differentiated
      N1E-115 cells and after distinct periods of differentiation, have been determined
      by the epifluorescence technique using the Fura-2-AM probe. The results of this
      quantitative assessment, revealed that N1E-115 cells which undergo neuronal
      differentiation for 48 hours in the presence of 1.5% DMSO are best qualified to
      be used to cover the interior of the nerve guides since the [Ca2+]i was not found
      to be elevated indicating thus that the onset the cell death processes was not
      occurred.

PMID- 16611537
TI  - Autologous stem cell transplantation in acute myeloid leukemia. Factors
      influencing outcome. A 13 year single institution experience.
AB  - We report our results of autologous stem cell transplantation (SCT) in patients
      with AML during the last 13 years. Between August 1990 and December 2003, 42
      patients with acute myeloid leukemia (AML) received an autologous SCT. Patients
      were classified as standard risk if first complete remission (CR) was induced
      after one or two chemotherapy regimens and the white blood cell count at
      presentation was below 50,000/mL (n=12), while patients requiring more than two
      induction regimens to attain first CR and with CR2 ou more advanced disease
      and/or had a higher white blood cell count at presentation were defined as high
      risk (n=30). Twenty one patients were transplanted in first CR. The median
      patient age was 24 years (range, 2-56 years), and the median time interval from
      diagnosis to autologous SCT was 9 months (range 3-87 months). The conditioning
      regimen for SCT consisted of busulfan (BU) 16 mg/kg and melfalan (MEL) 180 mg/m2
      (BUMEL) in 17 (40%) patients and busulfan 16 mg/kg and VP-16 60 mg/kg (BUVP16) in
      22 (52%) patients. Three patients received a different conditioning regimen with
      BCNU 300 mg/m2, VP16 2 g/m2 and melphalan 160 mg/m2 (BEM). Twenty five (60%)
      patients received bone marrow (BM), 11 (26%) patients received peripheral blood
      stem cells (PBSC) and 6 patients (14%) received BM plus PBSC. With a median
      follow-up of 7 years, the 13 year overall survival (OS) and diseasefree survival
      (DFS) of all patients is 52% and 40%, respectively. In univariate analysis, males
      had a significantly superior DFS than females (55% vs 22%, p=0.003), and patients
      younger than 15 years of age had significantly superior OS and DFS than older
      patients (50% vs 35%, p=0.05; and 50% vs 28%, p=0.03, respectively). Patients
      with FAB M3 subtype also had a superior OS than the other FAB subtypes (100% vs
      44%, p=0.05). There was a strong statistical correlation between risk group and
      survival. In fact, the patients with standard risk had a superior OS and DFS than
      those with high risk disease (67% vs 23%, p=0.0004; and 50% vs 27%, p=0.01,
      respectively). When patients with FAB M3 disease were excluded from the analysis,
      the group with standard risk continue to have a superior OS and DFS (67% vs 13%,
      p=0.008; and 50% vs 14%, p=0.02, respectively). We conclude that autologous SCT
      is an effective treatment in AML with the possibility of long survivorship,
      particularly in patients with standard risk disease.

PMID- 16611538
TI  - CYP2D6 genetic polymorphisms are associated with susceptibility to pituitary
      tumors.
AB  - Several polymorphisms of drug-metabolizing enzymes have been implicated in the
      susceptibility to tumor development. The role of the CYP2D6, GSTM1 and GSTT1
      genes has been extensively studied, with alleles conferring different metabolic
      efficiencies and tumor risk. We studied the relationship between the main
      polymorphisms of these genes and the susceptibility to develop pituitary tumors,
      by performing a case-control study comprising 235 patients and 256 controls which
      were genotyped by means of PCR-RFLP based assays. Frequencies of the CYP2D6*1 and
      of the poor metabolizer allele CYP2D6*4, were determined along with the
      frequencies of the GSTM1 and GSTT1 null genotypes. CYP2D6 genotype frequencies
      were similar in patients and controls (p=0.087). CYP2D6*1 and CYP2D6*4 allele
      frequencies were 83.8%, 16.2% in cases and 78.3%, 21.7% in controls, showing a
      significant difference between the two groups (p=0.012). There were no
      significant differences between the frequencies of the GSTM1 and GSTT1 null
      genotypes in both groups. No association was found between histological type and
      any of the studied polymorphisms. Our data suggest an association of the CYP2D6*1
      allele and the susceptibility to pituitary adenomas, which could be due to an
      increased metabolism of unidentified procarcinogens or to linkage disequilibrium
      with another gene involved in pituitary tumorigenesis.

PMID- 16611539
TI  - [Emotional intelligence, social support and affect regulation].
AB  - The aim of the present study was to gain additional information about the
      relationship between emotional intelligence, social support, and affectivity. The
      subjects were 64 university students who completed the short form of the Trait
      Meta-Mood Scale (TMMS-30), the Social Support Questionnaire, and the Multiple
      Affect Adjective Check List (MAACL). The results show that Social Support is high
      and significantly related with both Mood Repair, on one hand, and more Positive
      Affects and Sensation Seeking, on the other. These findings are consistent with
      the hypothesis that social support can be considered, somehow, as a way of mood
      repair; and thus not surprisingly is also associated with more Positive Affects
      and Sensation Seeking.

PMID- 16611540
TI  - [The endless bonds and the challenges to medicine].
AB  - This paper summons to contest some of the bonds that will be severed, probably,
      by the new eugenics, and may be repaired by narrative-based medicine, two of the
      most extreme and contradictory challenges to today's--and tomorrow's--medical
      practice. Accordingly, I intend to frame its development into the unbounded
      mathesis of biomedicine with the hindsight intention of questioning the
      foundations both of the ethical basis of the beginning of life medical decisions
      and of the end of life medical decisions. I will defend that, since clinical
      experience always embodies existential and anthropological density, and always
      has moral value, medical decision making seems not to be totally reducible to any
      algorithm or to the genetization of the live world.

PMID- 16611541
TI  - [The myth of Apollo and Marsyas. Artistic representations and anatomical
      studies].
AB  - The authors analyze an interesting sculpture found in the gardens of a 17th
      Century palace in Lisbon, representing the myth of Apollo and Marsyas, which led
      them to compare the details of the sculpture of the flayed satyr with the
      previous anatomic studies by Leonardo da Vinci (cc.1510-1530) or Vesalius
      (cc.1543). The photographic material obtained from the 17th century Italian
      sculpture presents amazing similitude with these, earlier, 16th century
      anatomical studies. As a complement to this study, the authors compare the
      sculptures with the artistic evidences, found throughout the world, of the 17th
      century interest for the representation of the myth of Apollo and Marsyas, which
      could be considered as a meaningful artistic movement of the Renaissance and neo
      classic art. Some of the artistic representations of surface anatomy depict other
      motives, as is the case of the self-portrait of Michelangelo, painted in the
      Sistine Chapel, in honour of St. Bartholomew.

PMID- 16611542
TI  - [Mycoplasmas: what is the role in human infections?].
AB  - Mycoplasmas, the common denomination of the Mycoplasma and Ureaplasma genera,
      represent a unique and complex group of microorganisms that has been ignored by
      the majority of diagnostic laboratories, not only because of its fastidious
      growth, absence of commercial media and of procedures for a rapid diagnosis, but
      most of all due to a clinical perception established for many years that these
      microorganisms are of minor importance. Recently, this situation has changed,
      because there s a better understanding of mycoplasmas clinical importance, they
      have been recently associated with Human Immunodeficiency Virus (HIV),
      complications in pregnant women and their neonates and with rheumatological
      disorders, resulting in a need to cure infected persons. The development of
      laboratory techniques that allows their culture and identification has
      contributed for a clarification of the role of these microorganisms as
      etiological agents or as co-factor of specific diseases. This article wishes to
      be, not only a revision of the main characteristics of the human mycoplasmas, but
      also to contribute for a better understanding of the diseases to which these
      fascinating microorganisms are associated and of the available diagnostic methods
      by the health professionals.

PMID- 16611543
TI  - [Erysipelas].
AB  - Erysipelas is an acute dermo-hypodermal infection (non necrotizing) of bacterial
      origin, mainly group A beta-haemolytic streptococcus. The lower limbs are
      affected in more than 80% of the cases and the identified risk factors are
      disruption of cutaneous barrier, lymphoedema and obesity. Diagnosis is clinical
      and based upon the association of an acute inflammatory plaque with fever,
      lymphangitis, adenopathy and leukocytosis. Bacteriology is usually not helpful
      because of low sensitivity or delayed positivity. In the atypical forms
      erysipelas must be distinguished from necrotizing fasciitis and acute vein
      thrombosis. Penicillin remains the gold standard treatment, although new drugs,
      given their pharmacodynamic profile, may be used. Recurrence is the main
      complication, being crucial the correct treatment of the risk factors.

PMID- 16611544
TI  - [Hypercalcemic crisis associated with primary hyperparathyroidism during
      pregnancy].
AB  - Primary hyperparathyroidism is a rare occurrence in pregnancy with significant
      risks to the mother and the foetus, witch is related to the level of serum
      calcium. A 41-year-old women, gravida 2, para 1, presented at 22 weeks gestation
      with nausea, vomiting and mild cognitive dysfunction associated with
      hypercalcemic crisis. The hypercalcemia was observed to be related to parathyroid
      hyperplasia that was surgically removed. Complete resolution of her
      symptomatology and hypercalcemia occurred postoperatively. The pregnancy was
      complicated with transient hypertension. A small for gestational age healthy male
      infant was delivered at term with no neonatal complications related with this
      pathology.

PMID- 16611545
TI  - [Thyrotoxic periodic paralysis: a case report].
AB  - Thyrotoxic periodic paralysis (TPP) is characterized by recurrent episodes of
      muscle weakness and hypokalemia associated with thyroid hyperactivity. Reported
      predominantly among individuals of Asian descent, TPP is a rare manifestation of
      hyperthyroidism in western populations. We describe a typical case of TPP in a 33
      year-old portuguese male, who presented with acute tetraparesis associated with
      hypokalemia (K+ 2.6 mEq/L). The patient had a 8-week history of several episodes
      of paraparesis of variable intensity; these attacks were usually nocturnal,
      preceded by strenuous exercise and resolved spontaneously after a few hours. The
      presence of tachycardia, weight loss, and goiter led to the diagnosis of Graves's
      disease. The correction of the hyperthyroid function with metimazol and
      propranolol prevented further episodes of muscle weakness. Thyrotoxic periodic
      paralysis should be considered in the differential diagnosis of acute episodes of
      motor paralysis in young patients. The maintenance of a euthyroid status is an
      essential part of management as this prevents the paralytic episodes.

PMID- 16611547
TI  - MALT structure and function in farm animals.
AB  - Mucosa-associated lymphoid tissue (MALT) is defined as an organized lymphoid
      tissue in the mucosa that samples antigens. The morphological characteristics
      that distinguish MALT from lymphoid infiltrates are discussed. MALT has been
      extensively investigated in laboratory animals, while knowledge in cattle, sheep,
      goats, pigs and horses that are summarized under the term farm animals in this
      review is fragmentary. Literature data about the distribution, morphology,
      function and involvement in infectious diseases of MALT in farm animals are
      described. The understanding of specific features of MALT in other species than
      laboratory animals is important for comparative research, in order to understand
      pathological and immunological processes in the respective species and as a
      potential route of vaccination of mucosal surfaces.

PMID- 16611548
TI  - Mucosal defence along the gastrointestinal tract of cats and dogs.
AB  - Diseases that are associated with infections or allergic reactions in the
      gastrointestinal and respiratory tracts are major causes of morbidity in both
      cats and dogs. Future strategies for the control of these conditions require a
      greater understanding of the cellular and molecular mechanisms involved in the
      induction and regulation of responses at the mucosal surfaces. Historically, the
      majority of the fundamental studies have been carried out in rodents or with
      tissues obtained from man, but the expanding range of reagents available for the
      study of farm and companion animals provides opportunities for study in a wider
      range of animals including cats and dogs. To date, these studies have tended to
      be focussed on characterising the cellular distributions in healthy animals and
      in groups of cats and dogs identified as having an increased risk of mucosal
      disturbance. Where species comparisons of mucosal immune systems have been made,
      the results have tended to be divided between monogastric and ruminant animals.
      It is then not surprising that the mucosal immune systems of both cats and dogs
      bear greatest similarity to that documented for man and pigs. For example, IgA is
      the dominant immunoglobulin in mucosal secretions of cats and dogs and oral
      tolerance can be induced following the introduction of novel antigens into the
      diet. Also like several other species, cats become transiently hypersensitive to
      the newly introduced dietary antigen prior to the establishment of tolerance. In
      contrast, there are a number of potentially important differences. In particular,
      there are significant differences between cats and dogs in the expression MHC
      class II molecules on gut epithelial cells. Similarly, it has been reported that
      cats have elevated numbers of intraepithelial lymphocytes (IEL) and that a
      proportion of these express surface IgM. It remains to be determined if these
      differences reflect the way in which the animals are maintained and if they may
      have greater biological significance.

PMID- 16611549
TI  - Immunity in the female sheep reproductive tract.
AB  - Immune surveillance in the female reproductive tract is dependent on the
      interplay of many factors that include the expression of pattern recognition
      receptors on epithelial cells, resident leukocyte populations and hormones, none
      of which are uniform. The lower reproductive tract must accommodate the presence
      of commensal organisms whereas the upper reproductive tract is sterile. However,
      the upper female reproductive tract has its own immunological challenge in that
      it must tolerate the presence of a semi-allogeneic fetus if pregnancy is to
      succeed. So, immune activation and effector mechanisms to control pathogens may
      be qualitatively and quantitatively different along the reproductive tract. Our
      knowledge of innate and adaptive immunity in the sheep is less comprehensive than
      that of human or mouse. Nevertheless, comparative studies suggest that there are
      likely to be conserved innate immune sensory mechanisms (e.g. Toll-like
      receptors) and defence mechanisms (anti-proteases, defensins) that combine to
      limit infection in its early stages while shaping the adaptive response that
      leads to immunological memory and long-term protection. There are many pathogens
      that target the reproductive tract, and in particular the placenta, where
      specialised immunoregulatory mechanisms are operational. Among such pathogens are
      bacteria belonging to the genera Chlamydia/Chlamydophila that chronically infect
      the reproductive tracts of sheep and humans and ultimately cause disease through
      inflammation and tissue damage. An understanding of the immunological
      microenvironment of the reproductive tract is important for the design of novel
      control strategies to control chlamydial disease.

PMID- 16611550
TI  - The avian lung-associated immune system: a review.
AB  - The lung is a major target organ for numerous viral and bacterial diseases of
      poultry. To control this constant threat birds have developed a highly organized
      lung-associated immune system. In this review the basic features of this system
      are described and their functional properties discussed. Most prominent in the
      avian lung is the bronchus-associated lymphoid tissue (BALT) which is located at
      the junctions between the primary bronchus and the caudal secondary bronchi. BALT
      nodules are absent in newly hatched birds, but gradually developed into the
      mature structures found from 6-8 weeks onwards. They are organized into distinct
      B and T cell areas, frequently comprise germinal centres and are covered by a
      characteristic follicle-associated epithelium. The interstitial tissue of the
      parabronchial walls harbours large numbers of tissue macrophages and lymphocytes
      which are scattered throughout tissue. A striking feature of the avian lung is
      the low number of macrophages on the respiratory surface under non-inflammatory
      conditions. Stimulation of the lung by live bacteria but not by a variety of
      bacterial products elicits a significant efflux of activated macrophages and,
      depending on the pathogen, of heterophils. In addition to the cellular components
      humoral defence mechanisms are found on the lung surface including secretory IgA.
      The compartmentalisation of the immune system in the avian lung into BALT and non
      BALT-regions should be taken into account in studies on the host-pathogen
      interaction since these structures may have distinct functional properties during
      an immune response.

PMID- 16611551
TI  - Lymphocyte migration studies.
AB  - For maintenance of immunity and tolerance, the organs and tissues of the organism
      are connected by migrating lymphoid cells. Understanding lymphocyte migration is
      essential for many disorders and diseases-- especially in the mucosa-lined
      organs. Detailed analyses of migrating lymphocytes have been performed in many
      species, especially in laboratory animals. However, important experiments in
      lymphocyte migration have been carried out in large animals, for example sheep,
      cattle and pigs. These species allow experimental procedures like in situ-organ
      labelling, lymphocyte retransfusion studies or lymph vessel cannulations. Such
      studies have made an important contribution to the understanding of the overall
      principles of lymphocyte migration especially in the mucosal immune system. Major
      results on the specific migration of naive and memory T cells through lymphoid
      organs, the re-distribution of gamma/delta T cells in the intestinal immune
      system and the emigration of newly produced B cells from the ileal Peyer's
      patches have been obtained in large animals. Since there are growing numbers of
      markers for large animals, and molecular biology methods are available in these
      species, experiments in large animals will be an essential tool for the
      understanding of lymphocyte migration especially in mucosal organs.

PMID- 16611552
TI  - Antigen presenting cells in mucosal sites of veterinary species.
AB  - The ability of antigen presenting cells, in particular dendritic cells, to
      integrate a variety of environmental signals, together with their ability to
      respond appropriately by initiating either tolerance or defensive immune
      responses make them cells of particular relevance and importance in the mucosal
      environment. They have been demonstrated in a variety of mucosal tissues in
      veterinary species and have been characterized to varying degrees, showing that
      fundamental immunological principles apply throughout all species, but also
      highlighting some species differences. A major advantage of carrying out
      immunological research in veterinary species is their size: it is possible to
      cannulate lymphatic ducts and obtain information about cell migration between
      different tissues. It is also possible to obtain pure populations of relatively
      rare cell types such as the plasmacytoid dendritic cells or mucosal dendritic
      cells ex vivo for the study of immune responses to diseases in their natural host
      and for other thorough functional studies. Two major myeloid antigen presenting
      cell (APC) (dendritic cells, DC) cell populations have been described in gut
      draining lymph and other mucosal sites in ruminants and pigs, characterised by
      the presence or absence of surface molecules, their enzyme profiles, their
      ability to phagocytose and their different potential as APC. There is evidence
      that one of these subsets has migrated from the diffuse mucosal tissue, where it
      is found as a phagocytic as well as stimulatory APC population, which in turn may
      be derived from blood macrophages. In addition, the presence and role in viral
      infection of the IFN-alpha producing plasmacytoid DC in mucosal tissue is
      discussed, based on studies in pigs.

PMID- 16611553
TI  - Role of intestinal epithelial cells in the innate immune defence of the pig
      intestine.
AB  - The intestinal epithelium serves as a dynamic barrier, which in the course of its
      normal function, maintains regulated uptake of nutrients and water while
      excluding potential pathogens. Over the past decade many studies have also
      revealed the immunological importance of intestinal epithelial cells (IEC). IEC
      have developed a variety of mechanisms to reduce the risk of infection by
      invasive pathogens or damage by toxic compounds. The effective maintenance of a
      physical barrier function is dependent on the establishment of well-organised
      intercellular junctions and a constant state of regeneration/renewal of the
      epithelium. IEC also participate in the innate immune responsiveness of the
      intestine by their ability to secrete mucus and antimicrobial peptides. IEC are
      also able to secrete cytokines and to respond to exogenous chemokines. This
      review summarises the current knowledge of the innate immune mechanisms developed
      by porcine IEC.

PMID- 16611554
TI  - Innate immunity of the bovine mammary gland.
AB  - Understanding the immune defenses of the mammary gland is instrumental in
      devising and developing measures to control mastitis, the major illness of dairy
      ruminants. Innate immunity is an extremely broad field for investigation, and
      despite decades of research, our present knowledge of the innate defenses of the
      udder is incomplete. Yet, information is being gained on the recognition of
      pathogens by the mammary gland, and on several locally inducible defenses. The
      contribution of mammary epithelial cells to local defenses and to the
      mobilization of leucocytes is under growing scrutiny. Interactions of mastitis
      causing bacteria such as Escherichia coli or Staphylococcus aureus and the
      mammary gland represents a suitable model for studies on innate immunity at an
      epithelium frontier. Powerful new research tools are radically modifying the
      prospects for the understanding of the interplay between the mammary gland innate
      defenses and mastitis-causing bacteria: genetic dissection of the immune
      response, microarray gene technology, transcriptomic methodologies and gene
      silencing by RNA interference will make possible the discovery of several of the
      key defense mechanisms which govern the susceptibility/resistance to mastitis at
      the molecular and genetic levels. It should then be possible to enhance the
      resistance of dairy ruminants to mastitis through immunomodulation and genetic
      improvement.

PMID- 16611555
TI  - The sheep and cattle Peyer's patch as a site of B-cell development.
AB  - In sheep and cattle, the ileal Peyer's patch (PP), which extends one-two meters
      along the terminal small intestine, is a primary lymphoid organ of B-cell
      development. B-cell diversity in the ileal PP is thought to develop by
      combinatorial mechanisms, gene conversion and/or point mutation. These species
      also have jejunal PP that function more like secondary lymphoid tissues concerned
      with mucosal immune reactions. These two types of PP differ significantly in
      their histology, ontogeny and the extent of lymphocyte traffic. The prenatal
      development of follicles in the PP begins first in the jejunum during the middle
      of gestation and then in the ileum during late gestation. B-cells proliferate
      rapidly in the ileal PP follicle; up to five percent of these cells survive while
      the majority dies by apoptosis, perhaps driven by the influence of environmental
      antigen and/or self-antigen. The surviving cells migrate from the ileal PP and
      populate the peripheral B-cell compartment. By adolescence, the ileal PP has
      involuted but the function of jejunal PP, compatible with a role as secondary
      lymphoid organ, continues throughout life. In this review, we focus on the
      development of PP as a site of B-cell repertoire generation, positive and
      negative B-cell selection, and the differences between ileal PP and jejunal PP.

PMID- 16611556
TI  - Development of the neonatal B and T cell repertoire in swine: implications for
      comparative and veterinary immunology.
AB  - Birth in all higher vertebrates is at the center of the critical window of
      development in which newborns transition from dependence on innate immunity to
      dependence on their own adaptive immunity, with passive maternal immunity
      bridging this transition. Therefore we have studied immunological development
      through fetal and early neonatal life. In swine, B cells appear earlier in fetal
      development than T cells. B cell development begins in the yolk sac at the 20th
      day of gestation (DG20), progresses to fetal liver at DG30 and after DG45
      continues in bone marrow. The first wave of developing T cells is gammadelta
      cells expressing a monomorphic Vdelta rearrangement. Thereafter, alphabeta T
      cells predominate and at birth, at least 19 TRBV subgroups are expressed, 17 of
      which appear highly homologous with those in humans. In contrast to the T cell
      repertoire and unlike humans and mice, the porcine pre-immune VH (IGHV-D-J)
      repertoire is highly restricted, depending primarily on CDR3 for diversity. The V
      KAPPA (IGKV-J) repertoire and apparently also the V-LAMBDA (IGLV-J) repertoire,
      are also restricted. Diversification of the pre-immune B cell repertoire of swine
      and the ability to respond to both T-dependent and T-independent antigen depends
      on colonization of the gut after birth in which colonizing bacteria stimulate
      with Toll-like receptor ligands, especially bacterial DNA. This may explain the
      link between repertoire diversification and the anatomical location of primary
      lymphoid tissue like the ileal Peyers patches. Improper development of adaptive
      immunity can be caused by infectious agents like the porcine reproductive and
      respiratory syndrome virus that causes immune dysregulation resulting in
      immunological injury and autoimmunity.

PMID- 16611557
TI  - The postnatal development of the mucosal immune system and mucosal tolerance in
      domestic animals.
AB  - The mucosal immune system is exposed to a range of antigens associated with
      pathogens, to which it must mount active immune responses. However, it is also
      exposed to a large number of harmless antigens associated with food and with
      commensal microbial flora, to which expression of active, inflammatory immune
      responses to these antigens is undesirable. The mucosal immune system must
      contain machinery capable of evaluating the antigens to which it is exposed and
      mounting appropriate effector or regulatory responses. Since the immune system is
      likely to have evolved initially in mucosal tissues, the requirement to prevent
      damaging allergic responses must be at least as old as the adaptive immune
      system, and studies of the mechanisms should include a range of non-mammalian
      species. Despite the importance for rational design of vaccines and for control
      of allergic reactions, the mechanisms involved are still largely unclear. It is
      not clear that the classical experimental protocol of "oral tolerance" is, in
      fact, measuring a biologically important phenomenon, nor is it clear whether
      tolerance is regulated in the evolutionarily recent organised lymphoid tissue
      (the lymph nodes) or the more ancient, diffuse architecture in the intestine. The
      capacity of the immune system to discriminate between "dangerous" and "harmless"
      antigens appears to develop with age and exposure to microbial flora. Thus, the
      ability of an individual or a group of animals to correctly regulate mucosal
      immune responses will depend on age, genetics and on their microbial environment
      and history. Attempts to manipulate the mucosal immune system towards active
      immune responses by oral vaccines, or towards oral tolerance, are likely to be
      confounded by environmentally-induced variability between individuals and between
      groups of animals.

PMID- 16611558
TI  - The IgA system: a comparison of structure and function in different species.
AB  - The predominant immunoglobulin isotype on most mucosal surfaces is secretory
      immunoglobulin A (SIgA), a polypeptide complex comprising two IgA monomers, the
      connecting J chain, and the secretory component. The molecular stability and
      strong anti-inflammatory properties make SIgA particularly well suited to provide
      protective immunity to the vulnerable mucosal surfaces by preventing invasion of
      inhaled and ingested pathogens. In contrast to SIgA, IgA in serum functions as an
      inflammatory antibody through interaction with FcalphaR on immune effector cells.
      Although IgA appears to share common features and protective functions in
      different species, significant variations exist within the IgA systems of
      different species. This review will give an overview of the basic concepts
      underlying mucosal IgA defence which will focus on the variations present among
      species in structure, antibody repertoire development, pIgR-mediated transport,
      colostral IgA content, hepatobiliary transport, and function with particular
      emphasis on the IgA system of the pig and dog. These interspecies variations
      emphasise the importance of elucidating and analysing the IgA system within the
      immune system of the species of interest rather than inferring roles from
      conclusions made in human and mouse studies.

PMID- 16611559
TI  - Lung inflammatory responses.
AB  - Inflammation is an important manifestation of respiratory disease in domestic
      animals. The respiratory system is mucosal in nature and has specific defense
      mechanisms used to control invasion by microbes and environmental elements.
      Inflammation can be beneficial or detrimental to the host. This article broadly
      discusses the primary mediators and mechanisms of inflammation within the
      respiratory tract of domestic animals. The role of cells, chemokines, cytokines
      and mediators in both acute and chronic inflammation are addressed. The
      pathogenesis of the initial insult determines the type of inflammation that will
      be induced, whether it is acute, chronic or allergic in origin. Maintenance of
      the microenvironment of cytokines and chemokines is critical for pulmonary
      homeostasis. Uncontrolled inflammation in the respiratory tract can be life
      threatening to the animal. The understanding of the mechanisms of inflammation,
      whether due to microbes or through inappropriate immune activation such as those
      occurring with allergies, is required to develop successful intervention
      strategies and control respiratory disease in animals.

PMID- 16611560
TI  - Mucosal delivery of vaccines in domestic animals.
AB  - Mucosal vaccination is proving to be one of the greatest challenges in modern
      vaccine development. Although highly beneficial for achieving protective
      immunity, the induction of mucosal immunity, especially in the gastro-intestinal
      tract, still remains a difficult task. As a result, only very few mucosal
      vaccines are commercially available for domestic animals. Here, we critically
      review various strategies for mucosal delivery of vaccines in domestic animals.
      This includes live bacterial and viral vectors, particulate delivery-systems such
      as polymers, alginate, polyphosphazenes, immune stimulating complex and
      liposomes, and receptor mediated-targeting strategies to the mucosal tissues. The
      most commonly used routes of immunization, strategies for delivering the antigen
      to the mucosal surfaces, and future prospects in the development of mucosal
      vaccines are discussed.

PMID- 16611561
TI  - Adjuvants modulating mucosal immune responses or directing systemic responses
      towards the mucosa.
AB  - In developing veterinary mucosal vaccines and vaccination strategies, mucosal
      adjuvants are one of the key players for inducing protective immune responses.
      Most of the mucosal adjuvants seem to exert their effect via binding to a
      receptor/or target cells and these properties were used to classify the mucosal
      adjuvants reviewed in the present paper: (1) ganglioside receptor-binding toxins
      (cholera toxin, LT enterotoxin, their B subunits and mutants); (2) surface
      immunoglobulin binding complex CTA1-DD; (3) TLR4 binding lipopolysaccharide; (4)
      TLR2-binding muramyl dipeptide; (5) Mannose receptor-binding mannan; (6) Dectin-1
      binding ss 1,3/1,6 glucans; (7) TLR9-binding CpG-oligodeoxynucleotides; (8)
      Cytokines and chemokines; (9) Antigen-presenting cell targeting ISCOMATRIX and
      ISCOM. In addition, attention is given to two adjuvants able to prime the mucosal
      immune system following a systemic immunization, namely 1alpha, 25(OH)2D3 and
      cholera toxin.

PMID- 16611562
TI  - A role of high impact weather events in waterborne disease outbreaks in Canada,
      1975 - 2001.
AB  - Recent outbreaks of Escherichia coli O157:H7, Campylobacter, and Cryptosporidium
      have heightened awareness of risks associated with contaminated water supply. The
      objectives of this research were to describe the incidence and distribution of
      waterborne disease outbreaks in Canada in relation to preceding weather
      conditions and to test the association between high impact weather events and
      waterborne disease outbreaks. We examined extreme rainfall and spring snowmelt in
      association with 92 Canadian waterborne disease outbreaks between 1975 and 2001,
      using case-crossover methodology. Explanatory variables including accumulated
      rainfall, air temperature, and peak stream flow were used to determine the
      relationship between high impact weather events and the occurrence of waterborne
      disease outbreaks. Total maximum degree-days above 0 degrees C and accumulated
      rainfall percentile were associated with outbreak risk. For each degree-day above
      0 degrees C the relative odds of an outbreak increased by a factor of 1.007 (95%
      confidence interval [CI] = 1.002 - 1.012). Accumulated rainfall percentile was
      dichotomized at the 93rd percentile. For rainfall events greater than the 93rd
      percentile the relative odds of an outbreak increased by a factor of 2.283 (95%
      [CI] = 1.216 - 4.285). These results suggest that warmer temperatures and extreme
      rainfall are contributing factors to waterborne disease outbreaks in Canada. This
      could have implications for water management and public health initiatives.

PMID- 16611563
TI  - Air particulate pollution due to bushfires and respiratory hospital admissions in
      Brisbane, Australia.
AB  - To examine the impact of bushfire smoke on hospital admission rates for
      respiratory disease, a time series study was conducted in Brisbane, Australia.
      Data on particles of 10 microns or less in aerodynamic diameter (PM10) per cubic
      metre, bushfire events, meteorological conditions, and daily respiratory hospital
      admissions were obtained for the period of 1 July 1997 to 31 December 2000. A
      generalized linear model with the negative binomial distribution was used to
      estimate the effects of bushfire smoke on respiratory hospital admissions. The
      results of this study show that daily respiratory hospital admission rates
      consistently increased with increasing levels of PM10 for both bushfire and non
      bushfire periods. This relationship appeared stronger during bushfire periods
      than non-bushfire periods, especially for the current day. The findings suggest
      that bushfire smoke was statistically significantly associated with an increased
      risk of respiratory hospital admissions in Brisbane (p < 0.05). The health impact
      assessment needs to be considered in the control and management of bushfires.

PMID- 16611564
TI  - Lung function in Pakistani wood workers.
AB  - The lung function impairment is the most common respiratory problem in industrial
      plants and their vicinity. Therefore, the purpose was to study the affects of
      wood dust and its duration of exposure on lung function. This was a matched cross
      sectional study of Spirometry in 46 non-smoking wood workers with age range 20 -
      60 years, who worked without the benefit of wood dust control ventilation or
      respiratory protective devices. Pulmonary function test was performed by using an
      electronic Spirometer. Significant reduction was observed in the mean values of
      Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), and
      Maximum Voluntary Ventilation (MVV) in wood workers relative to their matched
      controls. This impairment was increased with the duration of exposure to wood
      industries. It is concluded that lung function in wood workers is impaired and
      stratification of results shows a dose-response effect of years of wood dust
      exposure on lung function.

PMID- 16611565
TI  - Exposure pathways to HCH and DDT in Cidade dos Meninos and its surrounding
      districts of Amapa, Figueiras and Pilar, metropolitan regions of Rio de Janeiro,
      Brazil.
AB  - In 1989, the Rio de Janeiro State environmental agency (FEEMA) after a
      preliminary survey of the site known as Cidade dos Meninos, collected and
      disposed in a safe area tons of a pesticide that was spread in and around the
      ruins of an old hexachlorocyclohexane (HCH) factory. The aim of this article is
      three-fold: (i) To investigate the existing HCH and DDT contamination levels in
      soil, water, air, vegetables and grasses at the Cidade dos Meninos site and the
      surrounding districts of Amapa, Figueiras and Pilar; (ii) To identify the main
      environmental exposure pathways present in the study area, and (iii) To propose a
      health hazard classification for this area. The results showed the presence of
      high levels of total HCH and DDT in the environmental media samples, especially
      in those collected in the district Cidade dos Meninos. This district is also the
      one that produces more food (vegetables, milk and meat) for local and outside
      population. The environmental data correlated to the socio-economic, food diet
      and local health conditions led to the identification of four complete exposure
      pathways to HCH and DDT (surface soil, access road, food chain and ambient air).
      Using the ATSDR (1996) and Magalhaes (2000) criteria the site was classified in
      two public health hazard categories: Category II - hazard for public health, and
      category III - indeterminate hazard for public health.

PMID- 16611566
TI  - Eating out: consumer perceptions of food safety.
AB  - The purpose of this investigation was to improve the understanding of the
      public's perception of hygiene standards in eating places and their knowledge of
      the inspection system. A telephone survey found that despite many claiming
      experience of food poisoning, and a widely held belief that using eating places
      may result in illness, people continue to eat out or purchase takeaways
      regularly. Nearly all respondents claimed that the standard of food hygiene was
      important to them when deciding where to eat out. Assessments of hygiene
      standards were mainly based on aesthetics. A minority had concerns/complaints
      about the hygiene standards of eating places they had used. People do not appear
      to be well informed about the role of the local authorities in protecting food
      safety and how the food safety laws are enforced. They believe that they have the
      right to know the result of a hygiene inspection. Half of them thought that it
      was difficult to find information on the hygiene standards of eating places. If
      access to information was easier, some consumers would eat out more often. The
      public will need to be educated on the inspection and enforcement process if
      'scores on doors' is adopted as the main method of raising the confidence of the
      public in the standards of the food industry.

PMID- 16611567
TI  - Preventing diarrhoea with household ceramic water filters: assessment of a pilot
      project in Bolivia.
AB  - In an attempt to prevent diarrhoea in a rural community in central Bolivia, an
      international non-governmental organization implemented a pilot project to
      improve drinking water quality using gravity-fed, household-based, ceramic water
      filters. We assessed the performance of the filters by conducting a five-month
      randomized controlled trial among all 60 households in the pilot community. Water
      filters eliminated thermotolerant (faecal) coliforms from almost all intervention
      households and significantly reduced turbidity, thereby improving water
      aesthetics. Most importantly, the filters were associated with a 45.3% reduction
      in prevalence of diarrhoea among the study population (p = 0.02). After
      adjustment for household clustering and repeated episodes in individuals and
      controlling for age and baseline diarrhoea, prevalence of diarrhoea among the
      intervention group was 51% lower than controls, though the protective effect was
      only borderline significant (OR 0.49, 95% CI: 0.24, 1.01; p = 0.05). A follow-up
      survey conducted approximately 9 months after deployment of the filters found 67%
      being used regularly, 13% being used intermittently, and 21% not in use. Water
      samples from all regularly used filters were free of thermotolerant coliforms.

PMID- 16611568
TI  - The coaching schematic: validation through expert coach consensus.
AB  - Current research in coaching development infers that coaching is predominantly a
      decision-making process. The same and other research is not, however, informing
      the coaching development process due to a lack of a big picture approach.
      Consequently, there is a need for a model of coaching. In this paper, we offer
      such a model in the form of a schematic that reflects the coaching process from
      both a content and information-processing stance. To assess the validity of the
      schematic, 16 expert coaches were interviewed to elicit a complete description of
      their coaching process. The coaches were then shown a copy of the schematic and
      asked to comment on its design and content with respect to its accuracy in
      reflecting their coaching process. Following analysis of the interview, six
      general categories emerged: Roles, Goals, Typical Actions, Required Knowledge,
      Support for the Schematic, and Factors Influencing Development. The first four
      categories clearly displayed an implicit support for the schematic. Furthermore,
      all coaches offered explicit support for the schematic. Such strong support
      confirmed that the schematic was valid and could form the basis of focused
      interventions in coaching development.

PMID- 16611569
TI  - Motivational predictors of prosocial and antisocial behaviour in football.
AB  - This study examined (a) the main and interactive effects of goal orientations and
      perceived motivational climate on prosocial and antisocial behaviour, and (b)
      whether number of seasons one has played for the team interacts with motivational
      climate in predicting prosocial and antisocial behaviour in association football.
      Participants were 325 male association football players, whose age ranged from 12
      to 17 years. Athletes completed questionnaires measuring frequency of prosocial
      and antisocial behaviours in football, goal orientation, motivational climate and
      social desirability, and indicated the number of seasons they had played for
      their current team. Regression analyses revealed that task orientation and
      mastery climate were positive predictors of prosocial behaviour, whereas ego
      orientation and performance climate were positive predictors of antisocial
      behaviour. In addition, task orientation negatively predicted antisocial
      behaviour, while ego orientation negatively predicted prosocial behaviour. No
      significant interactions between task and ego orientation and mastery and
      performance motivational climate were found. Finally, mastery climate negatively
      predicted antisocial behaviour for those who had played many seasons for the
      team. In conclusion, strengthening task orientation and mastery climate and
      weakening ego orientation may enhance prosocial behaviour. However, for
      antisocial conduct to be eliminated from the context of association football, ego
      orientation and performance climate need to be tempered, as these constructs
      exert unique independent effects on antisocial behaviour.

PMID- 16611570
TI  - Physiological variables and performance markers of serving soldiers from two
      "elite" units of the British Army.
AB  - The aim of this study was to compare selected physiological variables and
      performance markers of soldiers from two "elite" units of the British Army. Ten
      soldiers from each of the two units were recruited for this study (n = 20). All
      participants completed three tests while carrying a 20 kg backpack load: (1) a
      maximal treadmill test using the Bruce protocol; (2) a 2 mile backpack run test
      specific to Unit A on a consistently flat tarmac road; and (3) a 29 km time-trial
      over hilly terrain typical of a mountainous area used by Unit B for performance
      assessment. Heart rate, maximal blood lactate concentration and performance (run
      time) were assessed during all three tests, with peak oxygen uptake also being
      measured during the maximal treadmill test. Measurements of anthropometry,
      isokinetic strength and mental toughness (MT48) were also recorded. There were no
      significant differences in terms of performance markers between the units (P >
      0.05). Performance on the maximal treadmill test correlated with performance on
      the 2 mile backpack run test (r = -0.57) and 29 km time-trial (r = -0.66).
      Performance on the 2 mile backpack run test in turn correlated with 29 km time
      trial performance (r = -0.77), accounting for 59% of the variance. In conclusion,
      the maximal treadmill test and the 2 mile backpack run test are useful indicators
      of performance on the arduous hill march and could be employed in the screening
      and selection of potential recruits.

PMID- 16611572
TI  - Molecular basis of substrate specificity in family 1 glycoside hydrolases.
AB  - ss-glycosidases are active upon a large range of substrates. Besides this, subtle
      changes in the substrate structure may result in large modifications on the ss
      glycosidase activity. The characterization of the molecular basis of ss
      glycosidases substrate preference may contribute to the comprehension of the
      enzymatic specificity, a fundamental property of biological systems. ss
      glycosidases specificity for the monosaccharide of the substrate nonreducing end
      (glycone) is controlled by a hydrogen bond network involving at least 5 active
      site amino acid residues and 4 substrate hydroxyls. From these residues, a
      glutamate, which interacts with hydroxyls 4 and 6, seems to be a key element in
      the determination of the preference for fucosides, glucosides and galactosides.
      Apart from this, interactions with the hydroxyl 2 are essential to the ss
      glycosidase activity. The active site residues forming these interactions and the
      pattern of the hydrogen bond network are conserved among all ss-glycosidases. The
      region of the ss-glycosidase active site that interacts with the moiety (called
      aglycone) which is bound to the glycone is formed by several subsites (1 to 3).
      However, the majority of the non-covalent interactions with the aglycone is
      concentrated in the first one, which presents a variable spatial structure and
      amino acid composition. This structural variability is in accordance with the
      high diversity of aglycones recognized by ss-glycosidases. Hydrophobic
      interactions and hydrogen bonds are formed with the aglycone, but the manner in
      which they control the ss-glycosidase specificity still remains to be determined.

PMID- 16611573
TI  - The structural and molecular biology of type III galactosemia.
AB  - Type III galactosemia is a genetic disease caused by mutations in the gene
      encoding UDP-galactose 4-epimerase. A variety of different point mutations
      located throughout the gene can be responsible. The main, disease-causing effects
      of these mutations appear to be a reduction in the catalytic rate constant (kcat)
      and an increase in the proteolytic sensitivity of the protein. Many of the
      mutations are distant from the active site of the enzyme and therefore must be
      assumed to affect the overall fold of the protein. Although the disease was
      previously classified into a severe, or generalized, form and an essentially
      benign, or peripheral, form this distinction has been blurred by recent work.
      Instead of two separate conditions it now appears that type III galactosemia is a
      continuum and that the symptoms will vary depending on the mutation(s) carried by
      the individual sufferer. This new way of looking at the disease has implications
      for the treatment and long term monitoring of patients.

PMID- 16611574
TI  - Is kinetoplastid pan-editing the result of an evolutionary balancing act?
AB  - Kinetoplastid U-insertion/deletion type editing is a highly elaborate process to
      generate translationally competent mitochondrial mRNAs. All evolutionary models
      to explain its origin and extent in present day organisms lack a convincing
      description of the advantage(s) responsible for an active increase of the editing
      potential. This advantage can be found in the gene fragmentation that is inherent
      in pan-editing which gives protection against loss of temporarily non expressed
      mitochondrial genes during periods of intense intraspecies competition.

PMID- 16611575
TI  - Phosphorylation of the alpha 2(1) procollagen promoter binding proteins is
      required for promoter activity.
AB  - We have previously identified transcription factors binding to the proximal
      promoter region of the human COL1A2 gene that are essential for promoter
      activity. Two regions in the proximal promoter, the CCAAT-element and the CME
      bind the CCAAT-binding factor and an as yet uncharacterized DNA-binding protein,
      respectively. In this study we show that phosphorylation of both the CCAAT
      binding and CME-binding proteins are essential for DNA-binding activity. While
      the binding of the CCAAT-binding proteins to the COL1A2 proximal promoter was
      inhibited after treatment of nuclear proteins with calf intestinal phosphatase,
      PP2A treatment had a significant inhibitory effect on the binding of the CME
      binding proteins. The treatment of type I collagen producing fibroblasts, CT-1,
      with the kinase inhibitor, staurosporine, interfered with DNA-protein
      interactions on both elements on the COL1A2 proximal promoter. This inhibition
      was associated with a significant decrease in both endogenous COL1A2 gene
      expression as observed by northern blot analysis and proximal promoter activity
      as assayed in transient transfection assays. Our results suggest that the
      phosphorylation of transcription factors interacting with the COL1A2 proximal
      promoter is essential for both DNA binding and for the expression of this gene.

PMID- 16611576
TI  - Foreword: lipid rafts/biophysics, cell signalling, trafficking and processing.

PMID- 16611577
TI  - Fluorescence-quenching and resonance energy transfer studies of lipid
      microdomains in model and biological membranes.
AB  - Measurements of contact-dependent fluorescence quenching and of fluorescence
      resonance energy transfer (FRET) within bilayers provide information concerning
      the spatial relationships between molecules on distance scales of a few nm or up
      a few tens of nm, respectively, and are therefore well suited to detect the
      presence and composition of membrane microdomains. As described in this review,
      techniques based on fluorescence quenching and FRET have been used to demonstrate
      the formation of nanoscale liquid-ordered domains in cholesterol-containing model
      membranes under physiological conditions, and to investigate the structural
      features of lipids and proteins that influence their partitioning between liquid
      ordered and liquid-disordered domains. FRET-based methods have also been used to
      test for the presence of 'raft' microdomains in the plasma membranes of mammalian
      cells. We discuss the sometimes divergent findings of these studies, possible
      modifications to the 'raft hypothesis' suggested by studies using FRET and other
      techniques, and the further potential of FRET-based methods to test and to refine
      current models of the nature and organization of membrane microdomains.

PMID- 16611578
TI  - Fluorescence correlation studies of lipid domains in model membranes.
AB  - Advances in optical microscopy techniques and single-molecule detection have
      paved the way to exploring new approaches for investigating membrane dynamics and
      organization, thereby revealing details on the processing of signals, complex
      association/dissociation, chemical reactions and transport at and around the
      membrane. These events rely on a tight regulation of lipid-protein and protein
      protein interactions in space and time. Fluorescence Correlation Spectroscopy
      (FCS) provides exquisite sensitivity in measuring local concentrations,
      association/dissociation constants, chemical rate constants and, in general, in
      probing the chemical environment of the species of interest and its interactions
      with potential partners. Here, we review some applications of FCS to lipid and
      protein organization in biomimetic membranes with lateral heterogeneities, which
      share some physico-chemical properties with cellular rafts. What we learn from
      investigations of lipid-lipid and lipid-protein interactions in simple model
      membranes can be regarded as an essential basic lecture for studies in more
      complex cellular membranes.

PMID- 16611579
TI  - Visualizing membrane microdomains by Laurdan 2-photon microscopy.
AB  - Lateral segregation of cell membrane components gives rise to microdomains with a
      different structure within the membrane. Most prominently, lipid rafts are
      defined as domains in liquid ordered phase whereas surrounding membranes are more
      fluid. Here we review a 2-photon fluorescence microscopy approach, which allows
      the visualization of membrane fluidity. The fluorescent probe Laurdan exhibits a
      blue shift in emission with increasing membrane condensation caused by an
      alteration in the dipole moment of the probe as a consequence of exclusion of
      water molecules from the lipid bilayer. The quantification of membrane order is
      achieved by the Generalized Polarization (GP) values, which are defined as
      normalized intensity ratios of two emission channels. GP images are therefore not
      biased by probe concentrations and membrane ruffles. Furthermore, Laurdan reports
      membrane structure independently from the lipid and protein cargo of the membrane
      domains. We give examples where Laurdan microscopy was instrumental in
      quantifying the formation of condensed membrane domains and their cellular
      requirements. Moreover we discuss how microdomains identified by Laurdan
      microscopy are consistent with domains identified by other methodologies and put
      GP images in the context of current raft hypotheses.

PMID- 16611581
TI  - Lipid rafts in lymphocyte activation and migration.
AB  - Functional polarization of leukocytes is a requisite to accomplish immune
      function. Immune synapse formation or chemotaxis requires asymmetric
      redistribution of membrane receptors, signaling molecules and the actin
      cytoskeleton. There is increasing evidence that compartmentalization of the
      plasma membrane into distinct lipid microdomains is pivotal in establishing and
      maintaining leukocyte polarity. Specific rafts assemble into large-scale domains
      to create plasma membrane asymmetries at specific cell locations, thus
      coordinating temporally and spatially cell signaling in these processes. In this
      review we discuss the roles of lipid rafts as organizers of T lymphocyte polarity
      during cell activation and migration.

PMID- 16611580
TI  - Lipid rafts in T cell receptor signalling .
AB  - The molecular events and the protein components that are involved in signalling
      by the T cell receptor (TCR) for antigen have been extensively studied.
      Activation of signalling cascades following TCR stimulation depends on the
      phosphorylation of the receptor by the tyrosine kinase Lck, which localizes to
      the cytoplasmic face of the plasma membrane by virtue of its post-translational
      modification. However, the precise order of events during TCR phosphorylation at
      the plasma membrane, remains to be defined. A current theory that describes early
      signalling events incorporates the function of lipid rafts, microdomains at the
      plasma membrane with distinct lipid and protein composition. Lipid rafts have
      been implicated in diverse biological functions in mammalian cells. In T cells,
      molecules with a key role in TCR signalling, including Lck, localize to these
      domains. Importantly, mutant versions of these proteins which fail to localise to
      raft domains were unable to support signalling by the TCR. Biochemical studies
      using purified detergent-resistant membranes (DRM) and confocal microscopy have
      suggested that upon stimulation, the TCR and Lck-containing lipid rafts may come
      into proximity allowing phosphorylation of the receptor. Further, there are data
      suggesting that phosphorylation of the TCR could depend on a transient increase
      in Lck activity that takes place within lipid rafts to initiate signalling.
      Current results and a model of how lipid rafts may regulate TCR signalling are
      discussed.

PMID- 16611582
TI  - Lipid raft organization and function in brush borders of epithelial cells.
AB  - Polarized epithelial cells of multicellular organisms confront the environment
      with a highly specialized apical cell membrane that differs in composition and
      function from that facing the internal milieu. In the case of absorptive cells,
      such as the small intestinal enterocyte and the kidney proximal tubule cell, the
      apical cell membrane is formed as a brush border, composed of regular, dense
      arrays of microvilli. Hydrolytic ectoenzymes make up the bulk of the microvillar
      membrane proteins, endowing the brush border with a huge digestive capacity.
      Several of the major enzymes are localized in lipid rafts, which, for the
      enterocyte in particular, are organized in a unique fashion. Glycolipids, rather
      than cholesterol, together with the divalent lectin galectin-4, define these
      rafts, which are stable and probably quite large. The architecture of these rafts
      supports a digestive/absorptive strategy for nutrient assimilation, but also
      serves as a portal for a large number of pathogens. Caveolae are well-known
      vehicles for internalization of lipid rafts, but in the enterocyte brush border,
      binding of cholera toxin is followed by uptake via a clathrin-dependent
      mechanism. Recently, 'anti-glycosyl' antibodies were shown to be deposited in the
      enterocyte brush border. When the antibodies were removed from the membrane,
      other carbohydrate-binding proteins, including cholera toxin, increased their
      binding to the brush border. Thus, anti-glycosyl antibodies may serve as
      guardians of glycolipid-based rafts, protecting them from lumenal pathogens and
      in this way be part of an ongoing 'cross-talk' between indigenous bacteria and
      the host.

PMID- 16611583
TI  - Lipid rafts and malaria parasite infection of erythrocytes.
AB  - Infection of human erythrocytes by the malarial parasite, Plasmodium falciparum,
      results in complex membrane sorting and signaling events in the mature
      erythrocyte. These events appear to rely heavily on proteins resident in
      erythrocyte lipid rafts. Over the past five years, we and others have undertaken
      a comprehensive characterization of major proteins present in erythrocyte
      detergent-resistant membrane lipid rafts and determined which of these proteins
      traffic to the host-derived membrane that bounds the intraerythrocytic parasite.
      The data suggest that raft association is necessary but not sufficient for
      vacuolar recruitment, and that there is likely a mechanism of active uptake of a
      subset of erythrocyte detergent-resistant membrane proteins. Of the ten
      internalized proteins, few have been evaluated for a role in malarial entry. The
      beta(2)-adrenergic receptor and heterotrimeric G protein G(s) signaling pathway
      proteins regulate invasion. The implications of these differences are discussed.
      In addition, the latter finding indicates that erythrocytes possess important
      signaling pathways. These signaling cascades may have important influences on in
      vivo malarial infection, as well as on erythrocyte membrane flexibility and
      adhesiveness in sickle cell anemia. With respect to malarial infection, host
      signaling components alone are not sufficient to induce formation of the malarial
      vacuole. Parasite proteins are likely to have a major role in making the
      intraerythrocytic environment conducive for vacuole formation. Such interactions
      should be the focus of future efforts to understand malarial infection of
      erythrocytes since host- and parasite-targeted interventions are urgently needed
      to combat this terrible disease.

PMID- 16611584
TI  - The prion protein and lipid rafts.
AB  - Prions are the causative agent of the transmissible spongiform encephalopathies,
      such as Creutzfeldt-Jakob disease in humans. In these prion diseases the normal
      cellular form of the prion protein (PrP(C)) undergoes a post-translational
      conformational conversion to the infectious form (PrP(Sc)). PrP(C) associates
      with cholesterol- and glycosphingolipid-rich lipid rafts through association of
      its glycosyl-phosphatidylinositol (GPI) anchor with saturated raft lipids and
      through interaction of its N-terminal region with an as yet unidentified raft
      associated molecule. PrP(C) resides in detergent-resistant domains that have
      different lipid and protein compositions to the domains occupied by another GPI
      anchored protein, Thy-1. In some cells PrP(C) may endocytose through caveolae,
      but in neuronal cells, upon copper binding to the N-terminal octapeptide repeats,
      the protein translocates out of rafts into detergent-soluble regions of the
      plasma membrane prior to endocytosis through clathrin-coated pits. The current
      data suggest that the polybasic region at its N-terminus is required to engage
      PrP(C) with a transmembrane adaptor protein which in turn links with the clathrin
      endocytic machinery. PrP(C) associates in rafts with a variety of signalling
      molecules, including caveolin-1 and Fyn and Src tyrosine kinases. The clustering
      of PrP(C) triggers a range of signal transduction processes, including the
      recruitment of the neural cell adhesion molecule to rafts which in turn promotes
      neurite outgrowth. Lipid rafts appear to be involved in the conformational
      conversion of PrP(C) to PrP(Sc), possibly by providing a favourable environment
      for this process to occur and enabling disease progression.

PMID- 16611585
TI  - Membrane microdomains, caveolae, and caveolar endocytosis of sphingolipids.
AB  - Caveolae are flask-shape membrane invaginations of the plasma membrane that have
      been implicated in endocytosis, transcytosis, and cell signaling. Recent years
      have witnessed the resurgence of studies on caveolae because they have been found
      to be involved in the uptake of some membrane components such as
      glycosphingolipids and integrins, as well as viruses, bacteria, and bacterial
      toxins. Accumulating evidence shows that endocytosis mediated by caveolae
      requires unique structural and signaling machinery (caveolin-1, src kinase),
      which indicates that caveolar endocytosis occurs through a mechanism which is
      distinct from other forms of lipid microdomain-associated, clathrin-independent
      endocytosis. Furthermore, a balance of glycosphingolipids, cholesterol, and
      caveolin-1 has been shown to be important in regulating caveolae endocytosis.

PMID- 16611586
TI  - The involvement of lipid rafts in Alzheimer's disease.
AB  - The amyloidogenesis occurring in Alzheimer's disease represents a fundamental
      membrane-related pathology involving a membrane-bound substrate metabolized by
      integral membrane proteases (secretases). Thus, the amyloid-beta peptide (Abeta),
      which accumulates extracellularly as plaques in the brains of Alzheimer's disease
      patients, is derived by sequential proteolytic cleavage of the integral
      transmembrane amyloid precursor protein (APP). Beta-Secretase or BACE-1 (beta
      site APP cleaving enzyme) is a transmembrane aspartic protease responsible for
      the first of these cleavage events, generating the soluble APP ectodomain
      sAPPbeta, and a C-terminal fragment CTFbeta. CTFbeta is subsequently cleaved by
      the ?gamma-secretase complex, of which presenilin is the catalytic core, to
      produce Ass. A variety of studies indicate that cholesterol is an important
      factor in the regulation of Ass production, with high cholesterol levels being
      linked to increased Ass generation and deposition. However, the mechanism(s)
      underlying this effect are unclear at present. Recent evidence suggests that
      amyloidogenic APP processing may preferentially occur in the cholesterol-rich
      regions of membranes known as lipid rafts, and that changes in cholesterol levels
      could exert their effects by altering the distribution of APP-cleaving enzymes
      within the membrane. Rafts may be involved in the aggregation of Ass and also in
      its clearance by amyloid-degrading enzymes such as plasmin or possibly neprilysin
      (NEP).

PMID- 16611587
TI  - Coding of visual information in the brain.

PMID- 16611588
TI  - Biologically motivated space-variant filtering for robust optic flow processing.
AB  - We describe and test a biologically motivated space-variant filtering method for
      decreasing the noise in optic flow fields. Our filter model adopts certain
      properties of a particular motion-sensitive area of the brain (area MT), which
      averages the incoming motion signals over receptive fields, the sizes of which
      increase with the distance from the center of the projection. We use heading
      estimation from optic flow as a criterion to evaluate the improvement of the
      filtered flow field. The tests are conducted on flow fields calculated with a
      standard flow algorithm from image sequences. We use two different sets of image
      sequences. The first set is recorded by a camera which is installed in a moving
      car. The second set is derived from a database containing three dimensional data
      and reflectance information from natural scenes. The latter set guarantees full
      control of the camera motion and ground truth about the flow field and the
      heading. We test the space-variant filtering method by comparing heading
      estimation results between space-variant filtered flow, flow filtered by
      averaging over domains of the visual field with constant size (constant
      filtering) and raw unfiltered flow. Because of noise and the aperture problem the
      heading estimates obtained from the raw flows are often unreliable. Estimated
      heading differs widely for different sub-sampled calculations. In contrast, the
      results obtained from the filtered flows are much less variable and therefore
      more consistent. Furthermore, we find a significant improvement of the results
      obtained from the space-variant filtered flow compared to the constant filtered
      flow. We suggest extensions to the space-variant filtering procedure that take
      other properties of motion representation in area MT into account.

PMID- 16611589
TI  - Local image structures and optic flow estimation.
AB  - Different kinds of local image structures (such as homogeneous, edge-like and
      junction-like patches) can be distinguished by the intrinsic dimensionality of
      the local signals. Intrinsic dimensionality makes use of variance from a point
      and a line in spectral representation of the signal in order to classify it as
      homogeneous, edge-like or junction-like. The concept of intrinsic dimensionality
      has been mostly exercised using discrete formulations; however, recent work has
      introduced a continuous definition. The current study analyzes the distribution
      of local patches in natural images according to this continuous understanding of
      intrinsic dimensionality. This distribution reveals specific patterns than can be
      also associated to local image structures established in computer vision and
      which can be related to orientation and optic flow features. In particular, we
      link quantitative and qualitative properties of optic-flow error estimates to
      these patterns. In this way, we also introduce a new tool for better analysis of
      optic flow algorithms.

PMID- 16611590
TI  - Movement-induced motion signal distributions in outdoor scenes.
AB  - The movement of an observer generates a characteristic field of velocity vectors
      on the retina (Gibson 1950). Because such optic flow-fields are useful for
      navigation, many theoretical, psychophysical and physiological studies have
      addressed the question how ego-motion parameters such as direction of heading can
      be estimated from optic flow. Little is known, however, about the structure of
      optic flow under natural conditions. To address this issue, we recorded sequences
      of panoramic images along accurately defined paths in a variety of outdoor
      locations and used these sequences as input to a two-dimensional array of
      correlation-based motion detectors (2DMD). We find that (a) motion signal
      distributions are sparse and noisy with respect to local motion directions; (b)
      motion signal distributions contain patches (motion streaks) which are
      systematically oriented along the principal flow-field directions; (c) motion
      signal distributions show a distinct, dorso-ventral topography, reflecting the
      distance anisotropy of terrestrial environments; (d) the spatiotemporal tuning of
      the local motion detector we used has little influence on the structure of motion
      signal distributions, at least for the range of conditions we tested; and (e)
      environmental motion is locally noisy throughout the visual field, with little
      spatial or temporal correlation; it can therefore be removed by temporal
      averaging and is largely over-ridden by image motion caused by observer movement.
      Our results suggest that spatial or temporal integration is important to retrieve
      reliable information on the local direction and size of motion vectors, because
      the structure of optic flow is clearly detectable in the temporal average of
      motion signal distributions. Ego-motion parameters can be reliably retrieved from
      such averaged distributions under a range of environmental conditions. These
      observations raise a number of questions about the role of specific environmental
      and computational constraints in the processing of natural optic flow.

PMID- 16611591
TI  - Integrating neuronal coding into cognitive models: predicting reaction time
      distributions.
AB  - Neurophysiological studies have examined many aspects of neuronal activity in
      terms of neuronal codes and postulated roles for these codes in brain processing.
      There has been relatively little work, however, examining the relationship
      between different neuronal codes and the behavioural phenomena associated with
      cognitive processes. Here, predictions about reaction time distributions derived
      from an accumulator model incorporating known neurophysiological data in temporal
      lobe visual areas of the macaque are examined. Results from human experimental
      studies examining the effects of changing stimulus orientation, size and contrast
      are consistent with the model, including qualitatively different changes in
      reaction time distributions with different stimulus manipulations. The different
      changes in reaction time distributions depend on whether the image manipulation
      changes neuronal response latency or magnitude and can be related to parallel or
      serial cognitive processes respectively. The results indicate that neuronal
      coding can be productively incorporated into computational models to provide
      mechanistic accounts of behavioural results related to cognitive phenomena.

PMID- 16611592
TI  - Learning from humans: computational modeling of face recognition.
AB  - In this paper, we propose a computational architecture of face recognition based
      on evidence from cognitive research. Several recent psychophysical experiments
      have shown that humans process faces by a combination of configural and component
      information. Using an appearance-based implementation of this architecture based
      on low-level features and their spatial relations, we were able to model aspects
      of human performance found in psychophysical studies. Furthermore, results from
      additional computational recognition experiments show that our framework is able
      to achieve excellent recognition performance even under large view rotations. Our
      interdisciplinary study is an example of how results from cognitive research can
      be used to construct recognition systems with increased performance. Finally, our
      modeling results also make new experimental predictions that will be tested in
      further psychophysical studies, thus effectively closing the loop between
      psychophysical experimentation and computational modeling.

PMID- 16611593
TI  - The microcirculation of skeletal muscle in aging.
AB  - Microvascular structure and function are key aspects of tissue and organ health.
      At approximately 40% of total body mass, skeletal muscle contains more
      microvessels than any other organ system in the body. Moreover, skeletal muscle
      is the most dynamic tissue in the body with the capacity to increase blood flow
      and metabolic rate 30- to 50- fold. Aging is associated with decrements in
      microvascular function and exercise tolerance that are poorly understood. Here,
      experts in their respective fields of microvascular structure and function are
      brought together to review the current state of knowledge regarding microvascular
      adaptations to aging. Reviews are drawn from human and animal studies and focus
      on age-related changes in sympathetic nervous system control of microvessels,
      capillary hemodynamics and oxygen pressure, microvascular network structure and
      functional integration, microvascular reactivity, whole muscle perfusion, and
      cellular contacts and inflammation.

PMID- 16611594
TI  - Alpha-adrenergic control of skeletal muscle circulation at rest and during
      exercise in aging humans.
AB  - Aging is associated with many changes in autonomic nervous system function that
      often lead to impairments in the normal ability to respond to physiological
      stressors commonly encountered in daily life. In addition, many of these chronic
      age-related changes in autonomic-circulatory function can potentially predispose
      the older adult to elevated risk for acute and chronic cardiovascular
      complications. One of the most pronounced and repeatable findings with respect to
      changes in the autonomic nervous system with human aging is the progressive
      increase in basal muscle sympathetic nerve activity (MSNA) directed to skeletal
      muscle vascular beds. Although the mechanism(s) underlying this sustained age
      associated increase in MSNA are not completely understood, several changes in
      sympathetic a-adrenergic function occur with age. In this review, the authors
      discuss how aging affects (1) a-adrenergic control of skeletal muscle vascular
      tone under resting conditions and the differences that exist in this control of
      the upper and lower limbs (forearm vs leg circulation); (2) vasoconstrictor
      responsiveness to endogenous norepinephrine release, as well as the specific
      responsiveness of postjunctional a(1)- and a(2)-adrenergic receptors; and (3)
      sympathetic a-adrenergic control of muscle blood flow and vascular tone during
      exercise in humans. Further, they discuss how these changes in sympathetic a
      adrenergic control of skeletal muscle blood vessels have important physiological
      and clinical implications for the aging human.

PMID- 16611595
TI  - Effect of aging on the structure and function of skeletal muscle microvascular
      networks.
AB  - Humans are active creatures, yet physical activity and activity tolerance decline
      over the life span. One prevailing theme in the literature to account for a
      portion of the reduced activity tolerance with aging is the observation that the
      capacity to augment blood flow to skeletal muscle may be impaired with advancing
      age. This dysfunction may be due to adaptations in the structure or function of
      their microvascular networks, which collectively determine blood flow resistance.
      The intent of this review is to present the current knowledge of structure and
      function of microvascular networks from skeletal muscle with special regard to
      how these may adapt to, or persist through, the aging process. Skeletal muscles
      are supplied by an intricate branching network of arterioles and venules. The
      consistency of findings among available studies suggests that the overall
      arteriolar and venular network branching topology establishes early in
      development and varies little, if at all, over the life span. Microvascular
      networks are not a series of functionally isolated segmental branches. Rather,
      these networks transmit and communicate vasomotor signals along their lengths and
      among their branches. Current evidence suggests that aging is associated with a
      decrement in the capacity of upstream vessels to respond to downstream
      vasodilation and signals transmitted cell-to-cell along the vascular wall.

PMID- 16611596
TI  - Effect of inflammation on the aging microcirculation: impact on skeletal muscle
      blood flow control.
AB  - To meet the metabolic demands of skeletal muscle, the vasculature supplying these
      vascular beds has to be connected to respond in a coordinated uniform manner,
      thus providing the necessary oxygen and nutrients during increased activity. The
      skeletal muscle microcirculation is the major resistance network controlling
      vascular blood supply and it is the integrity of the endothelium lining the blood
      vessels that is paramount in facilitating this action. Aging is a major risk
      factor for cardiovascular disease and is associated with significant increases in
      inflammatory agents that negatively impact the vasculature. Several inflammatory
      agents such as cytokines (tumor necrosis factor-a), advanced glycation products
      (AGEs), and matrix metalloproteinases (MMPs) along with storage cells for
      inflammatory mediators (mast cells) are associated with a chronic "low-grade
      inflammation" state that has been observed over the course of the aging process.
      Current research suggests that these age-related increases in inflammatory agents
      can disrupt the microvascular endothelium and thus impair blood flow. This
      impairment could exacerbate the common age-related disease states such as
      hypertension, diabetes, congestive heart failure, and sarcopenia, leading to
      increased mortality and morbidity.

PMID- 16611597
TI  - Vasodilation and vascular control in contracting muscle of the aging human.
AB  - There is accumulating evidence in humans that the control of blood flow to
      dynamically contracting skeletal muscle is altered with normal aging. Despite
      some inconsistencies in the literature, most healthy older subject groups studied
      to date (approximately 55-75 years) exhibited attenuated leg blood flow responses
      to moderate intensity leg exercise in comparison to younger (approximately 20-30
      years) controls. In most cases, older subjects also have higher arterial
      perfusion pressures at rest and at any submaximal workload than their younger
      counterparts, suggesting a heightened level of vasoconstriction in the legs that
      could result from structural and/or functional alterations within the arterial
      vasculature. The influence of age on vasodilator responsiveness in the
      contracting limbs of humans remains an open question, with reports of blunted,
      similar, and augmented increases in local vascular conductance during graded
      exercise in older vs. younger adults. Recent results from the authors' laboratory
      suggest that the ability of vascular smooth muscle in the legs to dilate in
      response to physiological and pharmacological stimuli is relatively well
      preserved with advancing age in men; however, a sex difference may exist in that
      older estrogen-deficient women exhibit blunted leg vasodilator responses compared
      to younger women. Potential mechanisms underlying altered vascular control within
      the resistance vasculature of contracting muscles of older men and women remain
      to be determined, but could include (1) fewer, smaller, and/or stiffer vessels,
      (2) impaired endothelium-dependent vasodilation, (3) augmented sympathetic
      vasoconstriction, (4) alterations in metabolic or myogenic control, and (5)
      reduced effectiveness of the skeletal muscle pump. Systematic research involving
      both humans and animal models will be necessary to fully elucidate the mechanisms
      underlying compromised muscle blood flow in old age.

PMID- 16611598
TI  - Aging-induced adaptations of microvascular reactivity.
AB  - Control of blood flow to skeletal muscle depends on the vasomotor tone present in
      the resistance vasculature. Although muscle blood flow has been shown to decline
      with advancing age, our knowledge of how alterations of reactivity of the
      resistance vasculature contribute to reduced delivery or altered distribution of
      blood in the aged is limited. Recent work has demonstrated that age alters the
      reactivity of resistance arteries and arterioles from skeletal muscle, and that
      impairment of both vasodilator and vasoconstrictor responses occurs with
      advancing age. The alterations in cellular mechanisms that contribute to age
      related impairment of vasoreactive responses encompass both the vascular
      endothelium and smooth muscle, and differ in muscles of varying function and
      fiber type. Current research suggests that some degree of age-induced endothelial
      dysfunction occurs in resistance arteries and arterioles from most skeletal
      muscle; however, the severity of endothelial impairment appears greater in
      resistance arteries and arterioles from highly oxidative locomotory muscles. Age
      related impairment of vasoconstrictor responses to metabolites and endogenous
      constrictor agents has also been documented. These age-related reductions in
      vasoreactivity that occur in the skeletal muscle resistance vasculature may
      contribute to inadequate delivery or distribution of blood flow during exercise
      and ultimately be a factor in loss of exercise capacity that occurs with
      advancing age.

PMID- 16611599
TI  - Fast computation of supertrees for compatible phylogenies with nested taxa.
AB  - Typically, supertree methods combine a collection of source trees in which just
      the leaves are labeled by taxa. In such methods the resulting supertree is also
      leaf labeled. An underlying assumption in these methods is that across all trees
      in the collection, no two of the taxa are nested; for example, "buttercups" and
      "plants" are nested taxa. Motivated by Page, the first supertree algorithm for
      allowing the source trees to collectively have nested taxa is called
      AncestralBuild. Here, in addition to taxa labeling the leaves, the source trees
      may have taxa labeling some of their interior nodes. Taxa-labeling interior nodes
      are at a higher taxonomic level than that of their descendants (for example,
      genera versus species). Analogous to the supertree method Build for deciding the
      compatibility of a collection of source trees in which just the leaves are
      labeled, AncestralBuild is a polynomial-time algorithm for deciding the
      compatibility of a collection of source trees in which some of the interior nodes
      are also labeled by taxa. Although a more general method, in this paper we show
      that the original description of AncestralBuild can be modified so that the
      running time is as fast as the current fastest running time for Build. Fast
      computation for deciding compatibility is essential if one is to make use of
      phylogenetic databases that contain thousands of trees on tens of thousands of
      taxa. This is particularly so as AncestralBuild is incorporated as a basic tool
      inside more general supertree methods (that is, methods that always output a tree
      regardless of the compatibility of the source trees). We apply the method to
      propose a comprehensive phylogeny of the strepsirrhines, a major group of the
      primates.

PMID- 16611600
TI  - Evolutionary rates, divergence dates, and the performance of mitochondrial genes
      in Bayesian phylogenetic analysis.
AB  - The mitochondrial genome is one of the most frequently used loci in phylogenetic
      and phylogeographic analyses, and it is becoming increasingly possible to
      sequence and analyze this genome in its entirety from diverse taxa. However,
      sequencing the entire genome is not always desirable or feasible. Which genes
      should be selected to best infer the evolutionary history of the mitochondria
      within a group of organisms, and what properties of a gene determine its
      phylogenetic performance? The current study addresses these questions in a
      Bayesian phylogenetic framework with reference to a phylogeny of plethodontid and
      related salamanders derived from 27 complete mitochondrial genomes; this topology
      is corroborated by nuclear DNA and morphological data. Evolutionary rates for
      each mitochondrial gene and divergence dates for all nodes in the plethodontid
      mitochondrial genome phylogeny were estimated in both Bayesian and maximum
      likelihood frameworks using multiple fossil calibrations, multiple data
      partitions, and a clock-independent approach. Bayesian analyses of individual
      genes were performed, and the resulting trees compared against the reference
      topology. Ordinal logistic regression analysis of molecular evolution rate, gene
      length, and the G-shape parameter a demonstrated that slower rate of evolution
      and longer gene length both increased the probability that a gene would perform
      well phylogenetically. Estimated rates of molecular evolution vary 84-fold among
      different mitochondrial genes and different salamander lineages, and mean rates
      among genes vary 15-fold. Despite having conserved amino acid sequences, cox1,
      cox2, cox3, and cob have the fastest mean rates of nucleotide substitution, and
      the greatest variation in rates, whereas rrnS and rrnL have the slowest rates.
      Reasons underlying this rate variation are discussed, as is the extensive rate
      variation in cox1 in light of its proposed role in DNA barcoding.

PMID- 16611601
TI  - Ancestral state reconstruction of body size in the Caniformia (Carnivora,
      Mammalia): the effects of incorporating data from the fossil record.
AB  - A recent molecular phylogeny of the mammalian order Carnivora implied large body
      size as the ancestral condition for the caniform subclade Arctoidea using the
      distribution of species mean body sizes among living taxa. "Extant taxa-only"
      approaches such as these discount character state observations for fossil members
      of living clades and completely ignore data from extinct lineages. To more
      rigorously reconstruct body sizes of ancestral forms within the Caniformia, body
      size and first appearance data were collected for 149 extant and 367 extinct
      taxa. Body sizes were reconstructed for four ancestral nodes using weighted
      squared-change parsimony on log-transformed body mass data. Reconstructions based
      on extant taxa alone favored large body sizes (on the order of 10 to 50 kg) for
      the last common ancestors of both the Caniformia and Arctoidea. In contrast,
      reconstructions incorporating fossil data support small body sizes (< 5 kg) for
      the ancestors of those clades. When the temporal information associated with
      fossil data was discarded, body size reconstructions became ambiguous,
      demonstrating that incorporating both character state and temporal information
      from fossil taxa unambiguously supports a small ancestral body size, thereby
      falsifying hypotheses derived from extant taxa alone. Body size reconstructions
      for Caniformia, Arctoidea, and Musteloidea were not sensitive to potential errors
      introduced by uncertainty in the position of extinct lineages relative to the
      molecular topology, or to missing body size data for extinct members of an entire
      major clade (the aquatic Pinnipedia). Incorporating character state observations
      and temporal information from the fossil record into hypothesis testing has a
      significant impact on the ability to reconstruct ancestral characters and
      constrains the range of potential hypotheses of character evolution. Fossil data
      here provide the evidence to reliably document trends of both increasing and
      decreasing body size in several caniform clades. More generally, including
      fossils in such analyses incorporates evidence of directional trends, thereby
      yielding more reliable ancestral character state reconstructions.

PMID- 16611602
TI  - Multiple sequence alignment accuracy and phylogenetic inference.
AB  - Phylogenies are often thought to be more dependent upon the specifics of the
      sequence alignment rather than on the method of reconstruction. Simulation of
      sequences containing insertion and deletion events was performed in order to
      determine the role that alignment accuracy plays during phylogenetic inference.
      Data sets were simulated for pectinate, balanced, and random tree shapes under
      different conditions (ultrametric equal branch length, ultrametric random branch
      length, nonultrametric random branch length). Comparisons between hypothesized
      alignments and true alignments enabled determination of two measures of alignment
      accuracy, that of the total data set and that of individual branches. In general,
      our results indicate that as alignment error increases, topological accuracy
      decreases. This trend was much more pronounced for data sets derived from more
      pectinate topologies. In contrast, for balanced, ultrametric, equal branch length
      tree shapes, alignment inaccuracy had little average effect on tree
      reconstruction. These conclusions are based on average trends of many analyses
      under different conditions, and any one specific analysis, independent of the
      alignment accuracy, may recover very accurate or inaccurate topologies. Maximum
      likelihood and Bayesian, in general, outperformed neighbor joining and maximum
      parsimony in terms of tree reconstruction accuracy. Results also indicated that
      as the length of the branch and of the neighboring branches increase, alignment
      accuracy decreases, and the length of the neighboring branches is the major
      factor in topological accuracy. Thus, multiple-sequence alignment can be an
      important factor in downstream effects on topological reconstruction.

PMID- 16611603
TI  - Utility of nuclear allele networks for the analysis of closely related species in
      the genus Carabus, subgenus Ohomopterus.
AB  - Nuclear DNA sequence data for diploid organisms are potentially a rich source of
      phylogenetic information for disentangling the evolutionary relationships of
      closely related organisms, but present special phylogenetic problems owing to
      difficulties arising from heterozygosity and recombination. We analyzed allelic
      relationships for two nuclear gene regions (phosphoenolpyruvate carboxykinase and
      elongation factor-1a), along with a mitochondrial gene region (NADH dehydrogenase
      subunit 5), for an assemblage of closely related species of carabid beetles
      (Carabus subgenus Ohomopterus). We used a network approach to examine whether the
      nuclear gene sequences provide substantial phylogenetic information on species
      relationships and evolutionary history. The mitochondrial gene genealogy strongly
      contradicted the morphological species boundary as a result of introgression of
      heterospecific mitochondria. Two nuclear gene regions showed high allelic
      diversity within species, and this diversity was partially attributable to
      recombination between various alleles and high variability in the intron region.
      Shared nuclear alleles among species were rare and were considered to represent
      shared ancestral polymorphism. Despite the presence of recombination, nuclear
      allelic networks recovered species monophyly more often and presented genetic
      differentiation patterns (low to high) among species more clearly. Overall,
      nuclear gene networks provide clear evidence for separate biological species and
      information on the phylogenetic relationships among closely related carabid
      beetles.

PMID- 16611604
TI  - Discriminating supported and unsupported relationships in supertrees using
      triplets.

PMID- 16611605
TI  - Goodbye Gondwana? New Zealand biogeography, geology, and the problem of
      circularity.

PMID- 16611610
TI  - Multiethnic perspectives on elder mistreatment.
AB  - PURPOSE: We conducted this study to understand the interpretations of elder
      mistreatment (EM) in multiethnic older adults. DESIGN AND METHODS: Focus group
      sessions were held with three ethnically homogenous groups (n = 18) and a group
      of elder care professionals (n = 6) eliciting responses to vignettes depicting
      various types of elder mistreatment. Qualitative analysis of focus group
      transcripts was performed to define EM occurrence, its severity, and to identify
      the perpetrator and victim. RESULTS: Four main categories emerged: social
      expectations, caregiver expectations, victim characteristics, and characteristics
      of the interaction. Themes included issues of gender roles, filial obligations,
      martial commitments, and ageism as features of the vignette discussions.
      Professional and lay caregiver issues were features of the caregiver
      expectations. Mental capacity, physical dependency, physical attributes, and
      complicity were the victim characteristics discussed. The characteristics of the
      interaction that were identified included resistance to care, retaliation,
      habitual occurrence, and perpetrator intent. IMPLICATIONS: Older adults identify
      multiple factors influencing the interpretation of elder mistreatment. These
      factors may determine strategies for future EM intervention.

PMID- 16611609
TI  - An exploratory study of abuse among frail elders using services in a small
      village in Japan.
AB  - PURPOSE: The purpose of this study was to explore the presence and form of elder
      abuse and to identify associated risk factors for abuse in a small sample of
      frail elders using support services in a suburban community in Japan. DESIGN AND
      METHODS: The participants were all frail elderly (n = 78) among a sample of
      persons aged 60 or older (n = 1,134) in an agricultural village on the main
      island of Japan. RESULTS: The key results were that 17.9% were categorized as
      being abused, with psychological abuse, neglect, and financial abuse being the
      most common forms. IMPLICATIONS: Cultural factors may impact who an abuser is,
      but the contributing factors in this Japanese sample do not significantly differ
      from results found in other countries. Preventive strategies need to be targeted
      at multiple levels.

PMID- 16611611
TI  - Elder mistreatment in urban India: a community based study.
AB  - This study examined the extent and correlates of elder mistreatment among 400
      community dwelling older adults aged 65 and above in Chennai, India. The
      prevalence rate of mistreatment was 14%. Chronic verbal abuse was the most common
      followed by financial abuse and the rate of physical abuse and neglect was
      similar. Among the mistreated, exactly half of them had experienced more than one
      type of mistreatment (multifaceted-mistreatment). With the exception of financial
      abuse, a significantly greater number of women experienced verbal and physical
      abuse as well as neglect compared to men. Adult children, daughters-in-law,
      spouses, and sons-in-law were the prominent perpetrators. The mistreated older
      adults were more depressed and less satisfied with life than those who were not
      mistreated. Logistic regression analysis revealed gender, social support, and
      subjective rating of physical health as significant factors associated with
      abuse.

PMID- 16611612
TI  - Lay persons' emotional reactions toward an abused elderly person.
AB  - This study examined lay persons' emotional reactions to abuse, with special
      attention to two types of disease: Alzheimer's disease and osteoporosis. A total
      of 169 adults (mean age = 60) were interviewed face-to-face using a vignette
      methodology. Although the majority of the participants found the vignette to
      describe a situation of abuse, one-quarter did not consider it an abusive
      situation. The person described in the vignette elicited more positive than
      negative emotions, with a high percentage of participants expressing sympathy,
      desire to help, and concern. The various emotional reactions to abuse are
      associated with different correlates.

PMID- 16611613
TI  - Sexual abuse resulting in HIV positivity in a patient with Alzheimer's disease: a
      case report from Trinidad and Tobago.

PMID- 16611614
TI  - Definitions and indicators of elder abuse: a delphi survey of APS caseworkers.
AB  - Instruments designed to measure specific types of elder mistreatment are not
      available, but they may be warranted after an initial screen indicates abuse or
      risk for abuse. The purpose of this study was to evaluate definitions for
      different types of elder mistreatment and validate the indicators as perceived by
      adult protective services (APS) caseworkers' opinions. Through 351 APS research
      network participants, a Delphi survey was completed. A 45% return rate was
      achieved for round one and 40% for round two with 70 same respondents from both
      rounds. These types of abuse, emotional abuse, exploitation of finances and/or
      property, neglect, physical abuse, and sexual abuse, have some similar and some
      extremely different indicators that singly and together expand their definition.
      Instruments to measure five different types of abuse are offered for caseworker
      or prevalence study use.

PMID- 16611615
TI  - Differentiating self-neglect as a type of elder mistreatment: how do these cases
      compare to traditional types of elder mistreatment?
AB  - Official estimates suggest that self-neglect is the most common type of elder
      mistreatment. Interestingly, very few researchers have empirically assessed self
      neglect as a type of elder mistreatment. In the current study, attention is given
      to how self-neglect cases handled by adult protective services agencies compare
      to other types of elder mistreatment. Comparisons are made between the needs of
      self-neglect clients and other protective services clients as well as the role of
      stress in the different types of abuse. Findings suggest that self-neglect
      clients are less likely to need help with certain functional activities. In
      addition, those who are married and those who have completed fewer years of
      education are less likely to be labeled as experiencing self-neglect. City
      differences in rates of self-neglect were also found. Not surprisingly, self
      neglect clients were more likely than other protective services clients to refuse
      services. Implications are provided.

PMID- 16611616
TI  - Age and gender differences and predictors of victimization of the older homeless.
AB  - Using data from the National Survey of Homeless Assistance Providers and Clients
      (NSHAPC) and an application of Felson's Routine Activities Theory, this paper
      examines gender and age differences in victimization experiences of a sample of
      more than 4,200 homeless and near-homeless people, mostly adults. Results suggest
      that there are no differences in victimization experience by homelessness status
      and that the negative relationship between age and victimization rates found in
      the general population is also found in the homeless population. However, the
      relationship is relatively weak and erratic, suggesting that homeless older
      adults who are at least 50 years old are at increased risk of becoming victims, a
      finding consistent with Routine Activities Theory. In addition, similar to
      research with other populations, younger homeless males are statistically more
      likely to report being victims of theft and physical assault while females of all
      ages are more likely to report being victims of sexual assault. However, for
      older homeless adults, the gender difference in likelihood of victimization
      disappears. Perhaps because older homeless women are labeled as easy targets,
      they were equally as likely as men to be victims of physical assault and theft in
      old age. This is also consistent with Routine Activities Theory.

PMID- 16611617
TI  - Caregiver burden, dementia, and elder abuse in South Korea.
AB  - The purpose of this study is to identify characteristics that would increase the
      likelihood that a Korean older adult with dementia being cared for by a family
      caregiver is at risk of being abused. This analysis was based on a sample of 481
      primary family caregivers from the data of Comprehensive Study for the Elderly
      Welfare Policy in Seoul (2003). Multiple regression analysis was used to examine
      predictors among the demographic characteristics of caregivers and care
      recipients, the severity of cognitive impairment, functional ability, caregiver
      burden, and social support for the degree of elder abuse. The degree of elder
      abuse was significantly associated with caregiver burden, mental impairment,
      dependency of daily living of care recipient, and use of formal services.

PMID- 16611618
TI  - Nursing home administrators' views of their own and volunteer resident advocates'
      enhancement of long-term care.
AB  - Volunteers perform much of the work of federally mandated state ombudsman
      programs which may include review of resident care in nursing facilities to
      protect against abuse and neglect. Although volunteers' activities may take place
      in the nursing facility, Nursing Home Administrators' (NHAs) views of their work
      are seldom studied. Data from questionnaires completed by 199 NHAs predicted
      enhancement (improvement) of long-term care by volunteer resident advocates.
      Administrators also described their advice for improvement of care. NHAs'
      perceptions of residents' pleasure and families' satisfaction with volunteers'
      visits were associated with enhancement of long-term care. Effectiveness
      attributed to volunteers' protection of rights and resolution of complaints was
      not related to perceived enhancement of long-term care. Answers to a number of
      remaining questions could enhance the efforts of volunteers in ombudsman
      programs, improve long-term care, and diminish opportunities for abuse.

PMID- 16611620
TI  - Neonatal exposure to higher brominated diphenyl ethers, hepta-, octa-, or
      nonabromodiphenyl ether, impairs spontaneous behavior and learning and memory
      functions of adult mice.
AB  - Polybrominated diphenyl ethers (PBDEs), used as flame retardants, have been shown
      to be increasing in the environment and in human mother's milk. We have earlier
      reported that lower brominated PBDEs, such as tetra-, penta-, and hexa-brominated
      diphenyl ethers, can cause developmental neurotoxic effects in mice. Recently,
      this was also observed with the full-brominated PBDE, deca-brominated diphenyl
      ether (PBDE 209), although it was suggested that the effects were caused by a
      (possibly debrominated) metabolite thereof. The present study revealed that
      2,2',3,3',4,4',5,5',6-nonabromodiphenyl ether (PBDE 206), 2,2',3,4,4',5,5',6
      octabromodiphenyl ether (PBDE 203), and to a minor extent also 2,2',3,4,4',5',6'
      heptabromodiphenyl ether (PBDE 183) can induce developmental neurotoxic effects.
      Neonatal Naval Medical Research Institute male mice were exposed on postnatal day
      3 or 10 to PBDE 206, PBDE 203, or PBDE 183, given as a single oral dose of 21
      mumol/kg body weight. At the adult age of 2-3 months, the mice were observed for
      performance in a spontaneous behavior test and the Morris water maze test. PBDE
      203 and PBDE 206, when administered on neonatal day 10, caused disturbances in
      spontaneous behavior, leading to disrupted habituation and a hyperactive
      condition in adults at the age of 2 months. These behavioral changes were also
      seen in 2-month-old mice exposed to PBDE 203 on neonatal day 3. Furthermore,
      exposure to PBDE 203 on neonatal day 10 affected learning and memory functions in
      adult mice. The developmental neurotoxic effects were most pronounced in mice
      exposed to PBDE 203. These developmental neurobehavioral defects were in
      agreement with those we observed previously with lower brominated PBDEs and with
      PBDE 209. It is important to consider the fact that different PBDE congeners can
      have differing degrees of potency, when comparing levels of PBDEs in the
      environment and in mother's milk.

PMID- 16611621
TI  - Effect of short-term drinking water exposure to dichloroacetate on its
      pharmacokinetics and oral bioavailability in human volunteers: a stable isotope
      study.
AB  - Dichloroacetic acid (DCAA) is a by-product of drinking water disinfection, is a
      known rodent hepatocarcinogen, and is also used therapeutically to treat a
      variety of metabolic disorders in humans. We measured DCAA bioavailability in 16
      human volunteers (eight men, eight women) after simultaneous administration of
      oral and iv DCAA doses. Volunteers consumed DCAA-free bottled water for 2 weeks
      to wash out background effects of DCAA. Subsequently, each subject consumed (12)C
      DCAA (2 mg/kg) dissolved in 500 ml water over a period of 3 min. Five minutes
      after the start of the (12)C-DCAA consumption, (13)C-labeled DCAA (0.3 mg/kg) was
      administered iv over 20 s and plasma (12)C/(13)C-DCAA concentrations measured at
      predetermined time points over 4 h. Volunteers subsequently consumed for 14
      consecutive days DCAA 0.02 microg/kg/day dissolved in 500 ml water to simulate a
      low-level chronic DCAA intake. Afterward, the (12)C/(13)C-DCAA administrations
      were repeated. Study end points were calculation of AUC(0-->infinity), apparent
      volume of distribution (V(ss)), total body clearance (Cl(b)), plasma elimination
      half-life (t((1/2),beta)), oral absorption rate (K(a)), and oral bioavailability.
      Oral bioavailability was estimated from dose-adjusted AUC ratios and by using a
      compartmental pharmacokinetic model after simultaneous fitting of oral and iv
      DCAA concentration-time profiles. DCAA bioavailability had large interindividual
      variation, ranging from 27 to 100%. In the absence of prior DCAA intake, there
      were no significant differences (p > 0.05) in any pharmacokinetic parameters
      between male and female volunteers, although there was a trend that women
      absorbed DCAA more rapidly (increased K(a)), and cleared DCAA more slowly
      (decreased Cl(b)), than men. Only women were affected by previous 14-day DCAA
      exposure, which increased the AUC(0-->infinity) for both oral and iv DCAA doses
      (p < 0.04 and p < 0.014, respectively) with a corresponding decrease in the
      Cl(b).

PMID- 16611622
TI  - The developmental neurotoxicity of fipronil: notochord degeneration and locomotor
      defects in zebrafish embryos and larvae.
AB  - Fipronil is a phenylpyrazole insecticide designed to selectively inhibit insect
      gamma-aminobutyric acid (GABA) receptors. Although fipronil is often used in or
      near aquatic environments, few studies have assessed the effects of this
      neurotoxicant on aquatic vertebrates at sensitive life stages. We explored the
      toxicological effects of fipronil on embryos and larvae using the zebrafish
      (Danio rerio) experimental model system. Embryos exposed to fipronil at nominal
      concentrations at or above 0.7 microM (333 mug/l) displayed notochord
      degeneration, shortening along the rostral-caudal body axis, and ineffective tail
      flips and uncoordinated muscle contractions along the body axis in response to
      touch. This phenotype closely resembles zebrafish locomotor mutants of the
      accordion class and is consistent with loss of reciprocal inhibitory
      neurotransmission by glycinergic commissural interneurons in the spinal cord.
      Consistent with the hypothesis that notochord degeneration may be due to abnormal
      mechanical stress from muscle tetany, the expression patterns of gene and protein
      markers specific to notochord development were unaffected by fipronil. Moreover,
      the degenerative effects of fipronil (1.1 microM) were reversed by coexposure to
      the sodium channel blocker MS-222 (0.6mM). The notochord effects of fipronil were
      phenocopied by exposure to 70 microM strychnine, a glycinergic receptor
      antagonist. In contrast, exposure to gabazine, a potent vertebrate GABA(A)
      antagonist, resulted in a hyperactive touch response but did not cause notochord
      degeneration. Although specifically developed to target insect GABA receptors
      with low vertebrate toxicity, our results suggest that fipronil impairs the
      development of spinal locomotor pathways in fish by inhibiting a structurally
      related glycine receptor subtype. This represents an unanticipated and
      potentially novel mechanism for fipronil toxicity in vertebrates.

PMID- 16611623
TI  - Nasal NPSH depletion and propylene oxide uptake in the upper respiratory tract of
      the mouse.
AB  - Propylene oxide is a nasal toxicant and weak site-of-contact carcinogen in the
      mouse and rat. To aid in inhalation risk assessment of this vapor and to provide
      data for comparison to the rat, the current study was aimed at providing
      quantitative information on upper respiratory tract (URT) dosimetry of this vapor
      in the mouse. Toward this end, uptake efficiencies of propylene oxide were
      measured in the surgically isolated URT of the male B6C3F1 mouse under constant
      velocity inspiratory flow conditions at flow rates of 12 and 50 ml/min and
      exposure concentrations of 25, 50, 100, 300, or 500 ppm. URT uptake efficiencies
      were measured continuously during 1 h exposure; mice were terminated immediately
      after exposure and nasal respiratory and olfactory mucosal nonprotein sulfhydryl
      (NPSH) levels were determined. Propylene oxide was scrubbed with moderate
      efficiency in the URT, with uptake efficiencies of < or = 33 and < or = 16% at
      the low and high inspiratory flow rates, respectively. Uptake efficiencies were
      slightly (approximately 5%) higher at low (25 or 50 ppm) than high (300 or 500
      ppm) exposure concentrations, suggesting that a saturable uptake pathway may
      exist. Nasal tissue NPSH levels were significantly depleted at exposure
      concentrations of 300 and 500 ppm but not at concentrations of 100 ppm or lower.
      Similar levels of NPSH depletion were observed in both nasal respiratory and
      olfactory mucosa. These data from mouse show some key differences when compared
      with those reported for the rat.

PMID- 16611624
TI  - c-Src is the primary signaling mediator of polychlorinated biphenyl-induced
      interleukin-8 expression in a human microvascular endothelial cell line.
AB  - Interleukin-8/CXCL8 (IL-8) is a prominent factor that modulates endothelial cell
      proliferation, migration, and angiogenesis. Therefore, the present study focused
      on the regulatory mechanisms of IL-8 expression induced by environmental
      pollutants such as polychlorinated biphenyls (PCBs). Treatment of human
      microvascular endothelial cells (HMECs) with specific PCB congener, 2,2',4,6,6'
      pentachlorobiphenyl (PCB 104), dose dependently increased levels of IL-8 mRNA and
      secreted protein. IL-8-neutralizing antibody inhibited migration of endothelial
      cells stimulated by conditioned media derived from PCB 104-treated HMECs. Site
      directed mutagenesis of the IL-8 promoter- and DNA-binding assays revealed that
      activator protein 1 (AP-1) and nuclear factor kappaB (NF-kappaB) sites are
      required for PCB 104-induced IL-8 transcription. Most importantly,
      pharmacological inhibition of Src kinase activity or overexpression of dominant
      negative c-src in HMECs resulted in a significant decrease in IL-8 expression and
      promoter activity. In contrast, ectopic expression of activated c-Src markedly
      increased promoter activity of IL-8. These stimulatory effects of dominant
      positive c-src were abrogated by mutagenesis of AP-1- and NF-kappaB-binding sites
      in the IL-8 promoter.

PMID- 16611625
TI  - Acetaminophen metabolism does not contribute to gender difference in its
      hepatotoxicity in mouse.
AB  - Gender is an important factor in pharmacokinetics and pharmacodynamics. In the
      current study, gender difference in acetaminophen (APAP)-induced hepatotoxicity
      has been examined. Male and female mice were injected with a toxic dose of APAP
      (500 mg/kg, ip). Female mice were resistant to the hepatotoxic effects of APAP,
      depicted by serum alanine aminotransferase and sorbital dehydrogenase activities
      and histological analysis. Basal hepatic reduced glutathione (GSH) levels were
      lower in females than in males, suggesting that basal GSH level may not be a
      factor in determining the gender difference of APAP hepatotoxicity. APAP
      metabolism was slower in females than males, revealed by lower levels of
      glucuronidation and sulfation and higher amounts of free APAP in the livers of
      female mice. Lower basal Cyp1a2 mRNA levels and lower expression of Cyp1a2 and
      Cyp3a11 mRNAs after APAP dosing were also observed in females compared with
      males. However, there was no gender difference in N-acetyl-p-benzoquinone imine
      covalent binding 2 h after APAP administration, suggesting similar APAP
      bioactivation between genders. Moreover, liver Gst pi mRNA levels were
      significantly lower in females than males. This finding is consistent with a
      previous report, which showed that Gst pi knockout mice are protected from APAP
      induced liver toxicity. In conclusion, gender difference of APAP-induced
      hepatotoxicity is not likely due to APAP metabolism. Perhaps, it is in part due
      to gender-dependent Gst pi expression. However, the mechanism underlying the
      association between reduction in Gst pi expression and hepatoprotective effect
      against APAP toxicity remains to be further explored.

PMID- 16611626
TI  - Topical application versus intranasal instillation: a qualitative comparison of
      the effect of the route of sensitization on trimellitic anhydride-induced
      allergic rhinitis in A/J mice.
AB  - Allergic airway diseases caused by low-molecular weight chemicals including
      trimellitic anhydride (TMA) have been linked to Th2 cytokines and are
      characterized by mucus hypersecretion and infiltration of lymphocytes and
      eosinophils into the airways. The most common route of human exposure to chemical
      respiratory allergens is inhalation. Most murine models, however, use topical
      exposure to sensitize mice. The present study tests the hypothesis that topical
      sensitization on the ears of mice with TMA will induce a qualitatively similar
      immunologic and pathologic response in the nasal airways after intranasal
      challenge to that induced after intranasal sensitization and challenge. A/J mice
      were sensitized topically or by intranasal instillation followed by intranasal
      challenge with TMA in an ethyl acetate/olive oil vehicle. Intranasal challenge
      with TMA in mice that were either topically or intranasally sensitized with TMA
      caused a marked allergic rhinitis, of similar severity, characterized by an
      influx of eosinophils and lymphocytes. Both the topical and intranasal routes of
      sensitization also caused significant increases in total serum IgE after
      intranasal challenge with TMA. In addition, both the topical and intranasal
      routes of sensitization caused significant increases in the mRNA expression of
      the Th2 cytokines IL-4, IL-5, and IL-13. Collectively, these findings suggest
      that topical application is effective in sensitizing mice to TMA and induces a
      nasal airway lesion and associated immune response after intranasal challenge,
      which is qualitatively similar to that induced by intranasal sensitization and
      challenge. Skin exposure may be a potential route of sensitization of the
      respiratory tract to chemical allergens.

PMID- 16611627
TI  - The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in
      breast cancer cells.
AB  - Estrogen plays a crucial role in the development of breast cancer, and the
      inhibition of estrogen synthesis has been an important target for the prevention
      and treatment of this disease. The rate-limiting reaction of the hormone
      biosynthesis is catalyzed by cytochrome P450 (CYP) 19 enzyme or aromatase. It has
      been of genuine interest to uncover an aromatase-inhibitory compound from a
      dietary source. Resveratrol is a polyphenolic compound that can be isolated from
      grape peel. Because of its structural resemblance to estrogen, resveratrol's
      agonistic and antagonistic properties on estrogen receptor have been examined and
      demonstrated. In the present study, the effect of resveratrol on the expression
      and enzyme activity of aromatase was investigated. By assaying on MCF-7 cells
      stably transfected with CYP19 (MCF-7aro cells), resveratrol inhibited the
      aromatase activity with an IC(50) value of 25 microM. Kinetic analysis indicated
      that both competitive and noncompetitive inhibition might be involved. The
      administration of 10 nmol/l testosterone-a substrate of aromatase-produced a 50%
      increase in the MCF-7aro cell number. This cell proliferation specifically
      induced by testosterone was significantly reduced by 10 microM resveratrol. In
      addition, 50 microM resveratrol significantly reduced the CYP19-encoding mRNA
      abundance in SK-BR-3 cells. The transcriptional control of CYP19 gene is tissue
      specific, and promoter regions I.3 and II have previously been shown to be
      responsible for CYP19 expression in breast cancer cells. Luciferase reporter gene
      assays revealed that resveratrol could repress the transcriptional control
      dictated by the promoter regulation. The present study illustrated that
      pharmacological dosage of resveratrol inhibited aromatase at both the enzyme and
      mRNA levels.

PMID- 16611628
TI  - Neurotoxicological interactions of a five-pesticide mixture in preweanling rats.
AB  - The estimation of risk following exposure to mixtures is an important feature of
      pesticide risk assessment. Also of concern is the potential for increased
      sensitivity of the young to pesticide toxicity. We have conducted interaction
      studies using a mixture of five organophosphorus (OP) pesticides (chlorpyrifos,
      diazinon, dimethoate, acephate, and malathion) in both adult (published
      previously) and preweanling rats using a fixed-ratio ray design. In the present
      study, cholinesterase inhibition and behavioral changes (motor activity, gait,
      and tail-pinch response) were measured in 17-day-old Long-Evans male rats
      following acute exposure to the OPs. The ratio of pesticides in the mixture
      reflected the relative dietary exposure estimates projected by the U.S.
      Environmental Protection Agency Dietary Exposure Evaluation Model. Dose-response
      data were collected for each OP alone, which were used (alone or in conjunction
      with the mixture data) to build an additivity model to predict the effects of the
      pesticide mixture along a ray of increasing total doses, using the same fixed
      ratio of components. The mixture data (full ray) were similarly modeled and
      statistically compared to the additivity model along the ray. Since malathion has
      been shown to produce synergistic interactions with certain OPs, it was of
      interest to evaluate the influence of malathion in this study. A second pesticide
      mixture, without malathion (reduced ray), was tested using the same dose levels
      of the remaining four OPs. Analysis of the full ray revealed significant greater
      than-additive responses for all endpoints. The magnitude of this shift ranged
      from two- to threefold for estimates of the ED(20) and ED(50). The deviation from
      additivity was also detected in the reduced ray for all but two endpoints (motor
      activity and tail-pinch response); however, for all endpoints, the reduced ray
      was significantly different from the full ray. Thus, greater-than-additive
      responses were detected in preweanling rats with this OP mixture, and this effect
      can only partially be attributed to the malathion in the mixture.

PMID- 16611629
TI  - Coordinate inhibition of cytokine-mediated induction of ferritin H, manganese
      superoxide dismutase, and interleukin-6 by the adenovirus E1A oncogene.
AB  - Adenovirus E1A sensitizes cells to the cytotoxic action of tumor necrosis factor
      alpha (TNF-alpha). This effect has been attributed to direct blockade of NF
      kappaB activation, as well as to increased activation of components of the
      apoptotic pathway and decreases in inhibitors of apoptosis. In this report we
      evaluated the mechanism by which E1A modulates the expression of the cytokine
      inducible cytoprotective genes manganese superoxide dismutase (MnSOD),
      interleukin-6 (IL-6), and ferritin heavy chain (FH). We observed that E1A blocks
      induction of MnSOD, IL-6, and FH by TNF-alpha or IL-1alpha. Because NF-kappaB
      plays a role in cytokine-dependent induction of MnSOD, IL-6, and FH, we assessed
      the effect of E1A on NF-kappaB in cells treated with TNF. IkappaB, the inhibitor
      of NF-kappaB, was degraded similarly in the presence and absence of E1A. TNF
      induced a quantitatively and temporally equivalent activation of NF-kappaB in
      control and E1A-transfected cells. However, TNF-dependent acetylation of NF
      kappaB was diminished in cells expressing E1A. E1A mutants unable to bind p400 or
      the Rb family proteins were still capable of repressing TNF-dependent induction
      of FH. However, mutants of E1A that abrogated binding of p300/CBP blocked the
      ability of E1A to repress TNF-dependent induction of FH. These results suggest
      that p300/CBP is a critical control point in NF-kappaB-dependent transcriptional
      regulation of cytoprotective genes by cytokines.

PMID- 16611630
TI  - ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein.
AB  - Loss of articular cartilage because of extracellular matrix breakdown is the
      hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix
      protein (COMP), a prominent noncollagenous matrix component in articular
      cartilage, have been observed in the cartilage, synovial fluid, and serum of
      arthritis patients. The molecular mechanism of COMP degradation and the enzyme(s)
      responsible for it, however, remain largely unknown. ADAMTS-12 (a disintegrin and
      metalloprotease with thrombospondin motifs) was shown to associate with COMP both
      in vitro and in vivo. ADAMTS-12 selectively binds to only the epidermal growth
      factor-like repeat domain of COMP of the four functional domains tested. The four
      C-terminal TSP-1-like repeats of ADAMTS-12 are shown to be necessary and
      sufficient for its interaction with COMP. Recombinant ADAMTS-12 is capable of
      digesting COMP in vitro. The COMP-degrading activity of ADAMTS-12 requires the
      presence of Zn2+ and appropriate pH (7.5-9.5), and the level of ADAMTS-12 in the
      cartilage and synovium of patients with both osteoarthritis and rheumatoid
      arthritis is significantly higher than in normal cartilage and synovium.
      Together, these findings indicate that ADAMTS-12 is a new COMP-interacting and 
      degrading enzyme and thus may play an important role in the COMP degradation in
      the initiation and progression of arthritis.

PMID- 16611631
TI  - Distinct priming kinases contribute to differential regulation of collapsin
      response mediator proteins by glycogen synthase kinase-3 in vivo.
AB  - Collapsin response mediator proteins (CRMPs) are a family of neuron-enriched
      proteins that regulate neurite outgrowth and growth cone dynamics. Here, we show
      that Cdk5 phosphorylates CRMP1, CRMP2, and CRMP4, priming for subsequent
      phosphorylation by GSK3 in vitro. In contrast, DYRK2 phosphorylates and primes
      CRMP4 only. The Cdk5 and DYRK2 inhibitor purvalanol decreases the phosphorylation
      of CRMP proteins in neurons, whereas CRMP1 and CRMP2, but not CRMP4,
      phosphorylation is decreased in Cdk5(-/-) cortices. Stimulation of neuroblastoma
      cells with IGF1 or TPA decreases GSK3 activity concomitantly with CRMP2 and CRMP4
      phosphorylation. Conversely, increased GSK3 activity is not sufficient to
      increase CRMP phosphorylation. However, the growth cone collapse-inducing protein
      Sema3A increases Cdk5 activity and promotes phosphorylation of CRMP2 (but not
      CRMP4). Therefore, inhibition of GSK3 alters phosphorylation of all CRMP
      isoforms; however, individual isoforms can be differentially regulated by their
      respective priming kinase. This is the first GSK3 substrate found to be regulated
      in this manner and may explain the hyperphosphorylation of CRMP2 observed in
      Alzheimer's disease.

PMID- 16611632
TI  - Functional consequences of a mutation in an expressed human alpha-cardiac actin
      at a site implicated in familial hypertrophic cardiomyopathy.
AB  - Point mutations in human alpha-cardiac actin cause familial hypertrophic
      cardiomyopathy. Functional characterization of these actin mutants has been
      limited by the lack of a high level expression system for human cardiac actin.
      Here, wild-type (WT) human alpha-cardiac actin and a mutant E99K actin have been
      expressed and purified from the baculovirus/insect cell expression system. Glu-99
      in subdomain 1 of actin is thought to interact with a positively charged cluster
      located in the lower 50-kDa domain of the myosin motor domain. Actin-activated
      ATPase measurements using the expressed actins and beta-cardiac myosin showed
      that the mutation increased the K(m) for actin 4-fold (4.7 +/- 0.7 mum for WT
      versus 19.1 +/- 3.0 mum for the mutant), whereas the V(max) values were similar.
      The mutation slightly decreased the affinity of actin for S1 in the absence of
      nucleotide, which can partly be accounted for by a slower rate of association.
      The in vitro motility for the E99K mutant was consistently lower than WT over a
      range of ionic strengths, which is likely related to the lower average force
      supported by the mutant actin. The thermal stability of the E99K was comparable
      to that of WT-actin, implying no folding defects. The lower density of negative
      charge in subdomain 1 of actin therefore weakens the actomyosin interaction
      sufficiently to decrease the force and motion generating capacity of E99K actin,
      thus providing the primary insult that ultimately leads to the disease phenotype.

PMID- 16611633
TI  - Characterization of mRNA interferases from Mycobacterium tuberculosis.
AB  - mRNA interferases are sequence-specific endoribonucleases encoded by the toxin
      antitoxin systems in the bacterial genomes. MazF from Escherichia coli has been
      shown to be an mRNA interferase that specifically cleaves at ACA sequences in
      single-stranded RNAs. It has been shown that MazF induction in E. coli
      effectively inhibits protein synthesis leading to cell growth arrest in the
      quasidormant state. Here we have demonstrated that Mycobacterium tuberculosis
      contains at least seven genes encoding MazF homologues (MazF-mt1 to -mt7), four
      of which (MazF-mt1, -mt3, -mt4, and -mt6) caused cell growth arrest when induced
      in E. coli. MazF-mt1 and MazF-mt6 were purified and characterized for their mRNA
      interferase specificities. We showed that MazF-mt1 preferentially cleaves the era
      mRNA between U and A in UAC triplet sequences, whereas MazF-mt6 preferentially
      cleaves U-rich regions in the era mRNA both in vivo and in vitro. These results
      indicate that M. tuberculosis contains sequence-specific mRNA interferases, which
      may play a role in the persistent dormancy of this devastating pathogen in human
      tissues.

PMID- 16611634
TI  - Active and passive mechanisms drive secretory granule biogenesis during
      differentiation of the intestinal parasite Giardia lamblia.
AB  - The parasitic protozoan Giardia lamblia undergoes important changes to survive
      outside the intestine of its host by differentiating into infective cysts. During
      encystation, three cyst wall proteins (CWPs) are specifically expressed and
      concentrated within encystation-specific secretory vesicles (ESVs). ESVs are
      electron-dense secretory granules that transport CWPs before exocytosis and
      extracellular polymerization into a rigid cyst wall. Because secretory granules
      form at the trans-Golgi in higher eukaryotes and because Giardia lacks an
      identifiable Golgi apparatus, the aim of this work was to investigate the
      molecular basis of secretory granule formation in Giardia by examining the role
      of CWPs in this process. Although CWP1, CWP2, and CWP3 are structurally similar
      in their 26-kDa leucine-rich overlapping region, CWP2 is distinguished by the
      presence of a 13-kDa C-terminal basic extension. In non-encysting trophozoites,
      expression of different CWP chimeras showed that the CWP2 basic extension is
      necessary for biogenesis of ESVs, which occurs in a compartment derived from the
      endoplasmic reticulum. Nevertheless, the CWP2 basic extension per se is
      insufficient to trigger ESV formation, indicating that other domains in CWPs are
      also required. We found that CWP2 is a key regulator of ESV formation by acting
      as an aggregation factor for CWP1 and CWP3 through interactions mediated by its
      conserved region. CWP2 also acts as a ligand for sorting via its C-terminal basic
      extension. These findings show that granule biogenesis requires complex
      interactions among granule components and membrane receptors.

PMID- 16611635
TI  - Homology modeling and site-directed mutagenesis of pyroglutamyl peptidase II.
      Insights into omega-versus aminopeptidase specificity in the M1 family.
AB  - Pyroglutamyl peptidase II (PPII), a highly specific membrane-bound
      omegapeptidase, removes N-terminal pyroglutamyl from thyrotropin-releasing
      hormone (<Glu-His-Pro-NH(2)), inactivating the peptide in the extracellular
      space. PPII and enzymes with distinct specificities such as neutral
      aminopeptidase (APN), belong to the M1 metallopeptidase family. M1
      aminopeptidases recognize the N-terminal amino group of substrates or inhibitors
      through hydrogen-bonding to two conserved residues (Gln-213 and exopeptidase
      motif Glu-355 in human APN), whereas interactions involved in recognition of
      pyroglutamyl residue by PPII are unknown. In rat PPII, the conserved exopeptidase
      residue is Glu-408, whereas the other one is Ser-269. Given that variations in M1
      peptidase specificity are likely due to changes in the catalytic region, we
      constructed three-dimensional models for the catalytic domains of PPII and APN.
      The models showed a salt bridge interaction between PPII-Glu-408 and PPII-Lys
      463, whereas the equivalent APN-Glu-355 did not participate in a salt bridge.
      Docking of thyrotropin-releasing hormone in PPII model suggested that the
      pyroglutamyl residue interacted with PPII-Ser-269. According to our models, PPII
      S269Q and -K463N mutations should leave Glu-408 in a physicochemical context
      similar to that found in M1 aminopeptidases; alternatively, PPII-S269E
      replacement might be sufficient to transform PPII into an aminopeptidase. These
      hypotheses were supported by site-directed mutagenesis; the mutants lost
      omegapeptidase but displayed alanyl-aminopeptidase activity. In conclusion,
      recognition of a substrate without an N-terminal charge requires neutralization
      of the aminopeptidase anionic binding site; furthermore, shortening of side chain
      at PPII-269 position is required for adjustment to the pyroglutamyl residue.

PMID- 16611636
TI  - Activity-based protein profiling implicates urokinase activation as a key step in
      human fibrosarcoma intravasation.
AB  - Entry of malignant cells into the vasculature (i.e. intravasation) requires
      proteolytic remodeling of the extracellular matrix so that tumor cells may pass
      through the local stroma and penetrate the vessel wall. The circulatory system
      then provides a means of transporting tumor cells to distant sites where they
      extravasate and establish metastatic lesions. This study utilizes activity-based
      protein profiling to compare the active serine hydrolase repertoire in high
      intravasating (HT-hi/diss) and low intravasating (HT-lo/diss) variants of the
      human fibrosarcoma HT-1080 cell line to determine which enzyme(s) play a role in
      intravasation. Activity-based protein profiling revealed multiple serine
      hydrolases with altered activity between HT-hi/diss and HT-lo/diss cells, with
      the largest difference being the activity of urokinase-type plasminogen activator
      (uPA). Levels of inactive uPA zymogen were similar between the two cell variants,
      but only HT-hi/diss conditioned medium contained active uPA, suggesting that uPA
      activation may contribute to the enhanced intravasation of HT-hi/diss cells. To
      analyze the role of uPA activity specifically in the process of intravasation, we
      grafted cells from the two HT-1080 variants onto the chorioallantoic membrane of
      chick embryos and measured levels of tumor cell intravasation in the distal
      chorioallantoic membrane using quantitative human-specific Alu PCR. Inhibition of
      uPA activity with natural (plasminogen activator inhibitor-1) or synthetic
      (amiloride) inhibitors diminished HT-hi/diss Matrigel invasion in vitro and
      intravasation and metastasis in vivo. Additionally, treatment of HT-lo/diss
      tumors with exogenous active uPA increased the number of intravasated cells in
      vivo. These results indicate that active uPA promotes tumor cell intravasation
      and that uPA activation appears to be a key step in tumor progression.

PMID- 16611637
TI  - Molecular cloning of the Leishmania major UDP-glucose pyrophosphorylase,
      functional characterization, and ligand binding analyses using NMR spectroscopy.
AB  - The dense glycocalyx surrounding the protozoan parasite Leishmania is an
      essential virulence factor. It protects the parasite from hostile environments in
      the sandfly vector and mammalian host and supports steps of development and
      invasion. Therefore, new therapeutic concepts concentrate on disturbing
      glycocalyx biosynthesis. Deletion of genes involved in the metabolism of
      galactose and mannose have been shown to drastically reduce Leishmania virulence.
      Here we report the identification of Leishmania major UDP-glucose
      pyrophosphorylase (UGP). UGP catalyzes the formation of UDP-glucose from glucose
      1-phosphate and UTP. This activation step enables glucose to enter metabolic
      pathways and is crucial for the activation of galactose. UDP-galactose is made
      from UDP-glucose by nucleotide-donor transfer to galactose 1-phosphate or by
      epimerization of the glucose moiety. Isolated in a complementation cloning
      approach, the activity of L. major UGP was proven in vitro. Moreover, purified
      protein was used to investigate enzyme kinetics, quaternary organization, and
      binding of ligands. Whereas sequestration by oligomerization is a known
      regulatory mechanism for eukaryotic UGPs, the recombinant as well as native L.
      major UGP migrated as monomer in size exclusion chromatography and in accord with
      this showed simple Michaelis-Menten kinetics toward all substrates. In saturation
      transfer difference (STD)-NMR studies, we clearly demonstrated that the molecular
      geometry at position 4 of glucose is responsible for substrate specificity.
      Furthermore, the gamma-phosphate group of UTP is essential for binding and for
      induction of the open conformation, which then allows entry of glucose 1
      phosphate. Our data provide the first direct proof for the ordered bi-bi
      mechanism suggested in earlier studies.

PMID- 16611638
TI  - Metabolism of myeloperoxidase-derived 2-chlorohexadecanal.
AB  - Numerous studies have suggested relationships between myeloperoxidase (MPO),
      inflammation, and atherosclerosis. MPO-derived reactive chlorinating species
      attack membrane plasmalogens releasing alpha-chloro fatty aldehydes including 2
      chlorohexadecanal (2-ClHDA), which have been found to accumulate in activated
      neutrophils, activated monocytes, infarcted myocardium and human atheromas. The
      present study employed synthetically prepared 2-Cl-[3H]-HDA as well as stable
      isotope-labeled 2-ClHDA to elucidate the metabolism of 2-ClHDA. The results
      herein demonstrate that human coronary artery endothelial cells oxidize and
      reduce 2-ClHDA to its respective chlorinated fatty acid (alpha-ClFA) and
      chlorinated fatty alcohol (alpha-ClFOH). Within the first hour of incubations of
      human coronary artery endothelial cells with 2-Cl-[3H]-HDA, the label was
      incorporated into the alpha-ClFOH and alpha-ClFA pools. After 1 h, the radiolabel
      was predominantly found in the alpha-ClFOH pool. Cell-derived alpha-ClFOH and
      alpha-ClFA were also released into the cell culture medium. Additionally,
      chlorinated fatty acid was incorporated into complex endothelial cell
      glycerolipids, including monoglycerides, triglycerides, phosphatidylcholine, and
      phosphatidylethanolamine. The oxidation and reduction of 2-ClHDA to alpha-ClFA
      and alpha-ClFOH, respectively, was further supported by mass spectrometric
      analyses of human coronary artery endothelial cells incubated with either 2-ClHDA
      or stable isotope-labeled 2-ClHDA (2-Cl-[d4]-HDA). 2-ClHDA was also oxidized to
      alpha-ClFA and reduced to alpha-ClFOH in both control and phorbol 12-myristate 13
      acetate-stimulated neutrophils. Taken together, these results show that a family
      of chlorinated lipidic metabolites is produced from alpha-chloro fatty aldehydes
      derived from reactive chlorinating species targeting of plasmalogens. These
      metabolites are incorporated into complex lipids and their biological roles may
      provide new insights into MPO-mediated disease.

PMID- 16611639
TI  - STAT3 as a downstream mediator of Trk signaling and functions.
AB  - Signal transducer and activator of transcription 3 (STAT3) has long been shown to
      regulate gene transcription in response to cytokines and growth factors. Recent
      evidence suggests that STAT3 activation may also occur downstream of receptor
      tyrosine kinase activation. In the current study we have identified STAT3 as a
      novel signal transducer for TrkA, the receptor-tyrosine kinase that mediates the
      functions of nerve growth factor (NGF). Activation of TrkA by NGF triggered STAT3
      phosphorylation at Ser-727, and enhanced the DNA binding and transcriptional
      activities of STAT3. More importantly, neurotrophin-induced increase in STAT3
      activation was observed to underlie several downstream functions of neurotrophin
      signaling. First of all, knockdown of STAT3 expression using the RNA interference
      approach attenuated NGF-induced transcription of immediate early genes in PC12
      cells. Furthermore, reduced STAT3 expression in PC12 cells suppressed NGF-induced
      cyclin D1 expression, thereby inhibiting growth arrest normally triggered by NGF
      treatment. Finally, inhibition of STAT3 expression decreased brain-derived
      neurotrophic factor-promoted neurite outgrowth in primary hippocampal neurons.
      Together, our findings have identified STAT3 as an essential component of
      neurotrophin signaling and functions.

PMID- 16611640
TI  - Crystal structure of mammalian cysteine dioxygenase. A novel mononuclear iron
      center for cysteine thiol oxidation.
AB  - Cysteine dioxygenase is a mononuclear iron-dependent enzyme responsible for the
      oxidation of cysteine with molecular oxygen to form cysteine sulfinate. This
      reaction commits cysteine to either catabolism to sulfate and pyruvate or the
      taurine biosynthetic pathway. Cysteine dioxygenase is a member of the cupin
      superfamily of proteins. The crystal structure of recombinant rat cysteine
      dioxygenase has been determined to 1.5-A resolution, and these results confirm
      the canonical cupin beta-sandwich fold and the rare cysteinyltyrosine
      intramolecular cross-link (between Cys(93) and Tyr(157)) seen in the recently
      reported murine cysteine dioxygenase structure. In contrast to the catalytically
      inactive mononuclear Ni(II) metallocenter present in the murine structure,
      crystallization of a catalytically competent preparation of rat cysteine
      dioxygenase revealed a novel tetrahedrally coordinated mononuclear iron center
      involving three histidines (His(86), His(88), and His(140)) and a water molecule.
      Attempts to acquire a structure with bound ligand using either cocrystallization
      or soaking crystals with cysteine revealed the formation of a mixed disulfide
      involving Cys(164) near the active site, which may explain previously observed
      substrate inhibition. This work provides a framework for understanding the
      molecular mechanisms involved in thiol dioxygenation and sets the stage for
      exploration of the chemistry of both the novel mononuclear iron center and the
      catalytic role of the cysteinyl-tyrosine linkage.

PMID- 16611641
TI  - Probes of the catalytic site of cysteine dioxygenase.
AB  - The first major step of cysteine catabolism, the oxidation of cysteine to
      cysteine sulfinic acid, is catalyzed by cysteine dioxygenase (CDO). In the
      present work, we utilize recombinant rat liver CDO and cysteine derivatives to
      elucidate structural parameters involved in substrate recognition and x-ray
      absorption spectroscopy to probe the interaction of the active site iron center
      with cysteine. Kinetic studies using cysteine structural analogs show that most
      are inhibitors and that a terminal functional group bearing a negative charge
      (e.g. a carboxylate) is required for binding. The substrate-binding site has no
      stringent restrictions with respect to the size of the amino acid. Lack of the
      amino or carboxyl groups at the alpha-carbon does not prevent the molecules from
      interacting with the active site. In fact, cysteamine is shown to be a potent
      activator of the enzyme without being a substrate. CDO was also rendered inactive
      upon complexation with the metal-binding inhibitors azide and cyanide. Unlike
      many non-heme iron dioxygenases that employ alpha-keto acids as cofactors, CDO
      was shown to be the only dioxygenase known to be inhibited by alpha
      ketoglutarate.

PMID- 16611642
TI  - Up-regulation of the angiotensin II type 1 receptor by the MAS proto-oncogene is
      due to constitutive activation of Gq/G11 by MAS.
AB  - Coexpression of the MAS proto-oncogene with the angiotensin II type 1 (AT(1))
      receptor in CHO-K1 cells has been reported to increase the number of
      [(3)H]angiotensin II-binding sites, although MAS does not bind [(3)H]angiotensin
      II. In HEK293 cells stably expressing AT(1) receptor-cyan fluorescent protein
      (CFP), MAS-yellow fluorescent protein (YFP) expression from an inducible locus
      caused strong up-regulation of AT(1) receptor-CFP amounts and [(3)H]angiotensin
      II binding levels. The time course of AT(1) receptor-CFP up-regulation was also
      markedly slower than that of induction of MAS expression. These effects were not
      mimicked by induced expression of I138D MAS-YFP, a mutant unable to cause
      constitutive loading of [(35)S]guanosine 5'-O-(thiotriphosphate) onto the
      phospholipase Cbeta-linked G protein Galpha(11). Protein kinase C (PKC)
      inhibitors and the selective Galpha(q)/Galpha(11) inhibitor YM-254890 fully
      blocked MAS-induced up-regulation of AT(1) receptor-CFP amounts, whereas the PKC
      activator phorbol 12-myristate 13-acetate produced strong up-regulation of AT(1)
      receptor-CFP without induction of MAS-YFP expression and in the presence of I138D
      MAS-YFP. The C-terminal tail of the AT(1) receptor is a known target for PKC
      mediated phosphorylation. In cells stably expressing a C-terminally truncated
      version of the AT receptor, induction of MAS expression did not up-regulate the
      truncated construct levels. These data demonstrate that the ability of MAS to up
      regulate AT(1) receptor levels reflects the constitutive capacity of MAS to
      activate Galpha(q)/Galpha(11) and hence stimulate PKC-dependent phosphorylation
      of the AT(1) receptor.

PMID- 16611643
TI  - LIM mineralization protein-1 potentiates bone morphogenetic protein
      responsiveness via a novel interaction with Smurf1 resulting in decreased
      ubiquitination of Smads.
AB  - Development and repair of the skeletal system and other organs is highly
      dependent on precise regulation of bone morphogenetic proteins (BMPs), their
      receptors, and their intracellular signaling proteins known as Smads. The use of
      BMPs clinically to induce bone formation has been limited in part by the
      requirement of much higher doses of recombinant proteins in primates than were
      needed in cell culture or rodents. Therefore, control of cellular responsiveness
      to BMPs is now a critical area that is poorly understood. We determined that LMP
      1, a LIM domain protein capable of inducing de novo bone formation, interacts
      with Smurf1 (Smad ubiquitin regulatory factor 1) and prevents ubiquitination of
      Smads. In the region of LMP responsible for bone formation, there is a motif that
      directly interacts with the Smurf1 WW2 domain and can effectively compete with
      Smad1 and Smad5 for binding. We have shown that small peptides containing this
      motif can mimic the ability to block Smurf1 from binding Smads. This novel
      interaction of LMP-1 with the WW2 domain of Smurf1 to block Smad binding results
      in increased cellular responsiveness to exogenous BMP and demonstrates a novel
      regulatory mechanism for the BMP signaling pathway.

PMID- 16611644
TI  - The chloroplast genome sequence of Chara vulgaris sheds new light into the
      closest green algal relatives of land plants.
AB  - The phylum Streptophyta comprises all land plants and six monophyletic groups of
      charophycean green algae (Mesostigmatales, Chlorokybales, Klebsormidiales,
      Zygnematales, Coleochaetales, and Charales). Phylogenetic analyses of four genes
      encoded in three cellular compartments suggest that the Charales are sister to
      land plants and that charophycean green algae evolved progressively toward an
      increasing cellular complexity. To validate this phylogenetic hypothesis and to
      understand how and when the highly conservative pattern displayed by land plant
      chloroplast DNAs (cpDNAs) originated in the Streptophyta, we have determined the
      complete chloroplast genome sequence (184,933 bp) of a representative of the
      Charales, Chara vulgaris, and compared this genome to those of Mesostigma
      (Mesostigmatales), Chlorokybus (Chlorokybales), Staurastrum and Zygnema
      (Zygnematales), Chaetosphaeridium (Coleochaetales), and selected land plants. The
      phylogenies we inferred from 76 cpDNA-encoded proteins and genes using various
      methods favor the hypothesis that the Charales diverged before the Coleochaetales
      and Zygnematales. The Zygnematales were identified as sister to land plants in
      the best tree topology (T1), whereas Chaetosphaeridium (T2) or a clade uniting
      the Zygnematales and Chaetosphaeridium (T3) occupied this position in alternative
      topologies. Chara remained at the same basal position in trees including more
      land plant taxa and inferred from 56 proteins/genes. Phylogenetic inference from
      gene order data yielded two most parsimonious trees displaying the T1 and T3
      topologies. Analyses of additional structural cpDNA features (gene order, gene
      content, intron content, and indels in coding regions) provided better support
      for T1 than for the topology of the above-mentioned four-gene tree. Our
      structural analyses also revealed that many of the features conserved in land
      plant cpDNAs were inherited from their green algal ancestors. The intron content
      data predicted that at least 15 of the 21 land plant group II introns were gained
      early during the evolution of streptophytes and that a single intron was acquired
      during the transition from charophycean green algae to land plants. Analyses of
      genome rearrangements based on inversions predicted no alteration in gene order
      during the transition from charophycean green algae to land plants.

PMID- 16611645
TI  - Average gene length is highly conserved in prokaryotes and eukaryotes and
      diverges only between the two kingdoms.
AB  - The average length of genes in a eukaryote is larger than in a prokaryote,
      implying that evolution of complexity is related to change of gene lengths. Here,
      we show that although the average lengths of genes in prokaryotes and eukaryotes
      are much different, the average lengths of genes are highly conserved within
      either of the two kingdoms. This suggests that natural selection has clearly set
      a strong limitation on gene elongation within the kingdom. Furthermore, the
      average gene size adds another distinct characteristic for the discrimination
      between the two kingdoms of organisms.

PMID- 16611646
TI  - Self-reported history of hypercholesterolaemia and gallstones and the risk of
      prostate cancer.
AB  - BACKGROUND: Although prostate cancer is one of the most common male cancers, its
      aetiology-and particularly the role of comorbidity-remains poorly understood.
      PATIENTS AND METHODS: Between 1991 and 2002, a case-control study on prostate
      cancer was conducted in Italy. This included 1294 men under the age of 75 years
      with incident, histologically confirmed prostate cancer, and 1451 controls,
      admitted to the same hospitals as cases for a wide spectrum of acute, non
      neoplastic diseases. The subjects' self-reported history of selected medical
      conditions was assessed through a structured and satisfactorily reproducible
      questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs)
      were obtained after allowance for major potential confounding factors. RESULTS: A
      significant direct relation was observed between hypercholesterolaemia and
      prostate cancer (OR = 1.51, 95% CI 1.23-1.85). This association was stronger (OR
      = 1.80) in older subjects (age > or =65) than in younger ones (OR = 1.32). A non
      significant excess risk of prostate cancer was also observed for gallstones (OR =
      1.26, 95% CI 0.93-1.70) and the relation was apparently stronger in patients with
      lower body mass index (OR = 1.59). CONCLUSIONS: This study suggests a possible
      relation between hypercholesterolaemia and prostate cancer.

PMID- 16611647
TI  - Unstudied infants: outcomes of moderately premature infants in the neonatal
      intensive care unit.
AB  - BACKGROUND: Newborns of 30-34 weeks gestation comprise 3.9% of all live births in
      the United States and 32% of all premature infants. They have been studied much
      less than very low birthweight infants. OBJECTIVE: To measure in-hospital
      outcomes and readmission within three months of discharge of moderately premature
      infants. DESIGN: Prospective cohort study including retrospective chart review
      and telephone interviews after discharge. SETTING: Ten birth hospitals in
      California and Massachusetts. PATIENTS: Surviving moderately premature infants
      born between October 2001 and February 2003. MAIN OUTCOME MEASURES: (a)
      Occurrence of assisted ventilation during the hospital stay after birth; (b)
      adverse in-hospital outcomes-for example, necrotising enterocolitis; (c)
      readmission within three months of discharge. RESULTS: With the use of
      prospective cluster sampling, 850 eligible infants and their families were
      identified, randomly selected, and enrolled. A total of 677 families completed a
      telephone interview three months after hospital discharge. During the birth stay,
      these babies experienced substantial morbidity: 45.7% experienced assisted
      ventilation, and 3.2% still required supplemental oxygen at 36 weeks. Readmission
      within three months occurred in 11.2% of the cohort and was higher among male
      infants and those with chronic lung disease. CONCLUSIONS: Moderately premature
      infants experience significant morbidity, as evidenced by high rates of assisted
      ventilation, use of oxygen at 36 weeks, and readmission. Such morbidity deserves
      more research.

PMID- 16611648
TI  - Contribution of IL-18-induced innate T cell activation to airway inflammation
      with mucus hypersecretion and airway hyperresponsiveness.
AB  - Human bronchial asthma is characterized by airway hyperresponsiveness (AHR),
      eosinophilic airway inflammation, mucus hypersecretion and high serum level of
      IgE. IL-18 was originally regarded to induce T(h)1-related cytokines from Th1
      cells in the presence of IL-12. However, our previous reports clearly
      demonstrated that IL-18 with IL-2 promotes Th2 cytokines production from T cells
      and NK cells. Furthermore, IL-18 with IL-3 stimulates basophils and mast cells to
      produce Th2 cytokines. Thus, we examined the capacity of IL-2 and IL-18 to induce
      AHR, airway eosinophilic inflammation and goblet cell metaplasia. Intranasal
      administration of IL-2 and IL-18 induces AHR, mucus hypersecretion and
      eosinophilic inflammation in the lungs of naive mice. CD4+ T cells are
      prerequisite for this IL-2 plus IL-18-induced bronchial asthma, because CD4+ T
      cells-depleted or Rag-2-deficient (Rag-2-/-) mice did not develop bronchial
      asthma after IL-2 plus IL-18 treatment. Both STAT6-/- mice and IL-13-neutralized
      wild-type mice failed to develop AHR, goblet cell metaplasia and airway
      eosinophilic inflammation, while IL-4-/- mice almost normally developed,
      suggesting that IL-13 is a major causative factor and IL-4 mainly enhances the
      degree of AHR and eosinophilic inflammation. Both IL-4 and IL-13 equally induce
      eotaxin in mouse embryonic fibroblasts. However, only IL-13 blockade inhibited
      asthma symptoms, suggesting that IL-13 but not IL-4 is produced abundantly and
      plays a critical role in the pathogenesis of bronchial asthma in this model. As
      airway epithelial cells store robust IL-18, IL-18 might be critically involved in
      pathogen-induced bronchial asthma, in which pathogens stimulate epithelial cells
      to produce IL-18 without IL-12 induction.

PMID- 16611649
TI  - IL-4 influences the differentiation and the susceptibility to activation-induced
      cell death of human naive CD8+ T cells.
AB  - It is now well established that the cytokine environment influences the
      activation, differentiation, proliferation and death of T lymphocytes during the
      primary response to antigen. Using an in vitro model, we investigated the
      influence of IL-4, added at the onset of TCR stimulation, on phenotypic and
      functional markers of naive CD8+ T cell activation including the up-regulation of
      activation markers, proliferation as well as the susceptibility to activation
      induced cell death (AICD). We report that IL-4, unlike IL-2 added at the onset of
      repeated TCR stimulation of naive CD8+ T cells prevents AICD, in part due to its
      ability to maintain the level of the survival-related protein Bcl-2. Moreover,
      TCR-triggered activation of naive CD8+ T cells in the presence of IL-4 leads to
      the development of a CD8+ T cell subset that proliferates normally, but which
      fails to exhibit characteristic activation parameters such as the up-regulation
      of CD25 and Granzyme B. Taken together, these results demonstrate that exposure
      to IL-4 during primary activation influences CD8+ T cell differentiation by
      inducing the development of a sub-population of AICD-resistant, proliferation
      competent cells that do not show some of the typical features of CD8+ T cell
      activation.

PMID- 16611650
TI  - Variations in cardiac interventions: doctors' practices and views.
AB  - OBJECTIVES: To investigate referral rates for cardiac interventions by clinical
      specialty, to document doctors' reasons for referrals and to explore doctors'
      perceptions of the factors that influenced their clinical decisions. STUDY
      DESIGN: Doctors completed a clinical decision-making exercise involving, in
      total, 6093 electronic patients with cardiac disease, and subsequently took part
      in the semi-structured interviews about influences on their decisions. Interviews
      were audio-recorded, transcribed and coded using a thematic approach, with the
      coding categories derived from the data. STUDY SETTING: Eighty-eight doctors
      (GPs, care-of-the-elderly specialists, cardiologists) participated in the full
      study, in seven areas in southern, central and northern England. Complete
      interview data were analysed for 76 of these. PRINCIPAL FINDINGS: Not all
      patients who were eligible for specific investigations or treatment received
      these. The extent of variations in clinical decisions differed by type of
      intervention. Apart from the general reasons for referrals, doctors raised nine
      main influences on their actual decision making. The most commonly reported
      influence ('barrier') was poor access to equipment for intervention, which
      increased thresholds for investigation and treatment. CONCLUSIONS: The current
      emphasis on achieving targets in the British NHS has led to a focus on easily
      measurable, but crude, process targets such as waiting lists. This study points
      to the need to include a broader quality assurance element to investigate the
      cluster of system failures which lead to variations in clinical decisions and
      thereby to inequitable treatment.

PMID- 16611651
TI  - Nontuberculous mycobacterial disease and Aspergillus-related lung disease in
      bronchiectasis.
AB  - The aim of the present study was to determine whether patients with
      bronchiectasis and nontuberculous mycobacteria (NTM) have a higher prevalence of
      Aspergillus-related lung disease. A series of 30 consecutive patients with
      bronchiectasis and NTM (cases) were compared with 61 patients with bronchiectasis
      and no evidence of NTM (controls). Aspergillus serology and computerised
      tomography of the thorax were used to identify Aspergillus-related lung diseases,
      including aspergilloma, allergic bronchopulmonary aspergillosis and chronic
      necrotising pulmonary aspergillosis. The rate of positive Aspergillus serology
      was higher in cases with NTM disease compared with controls (10 out of 30 versus
      six out of 61). The radiological features of Aspergillus-related lung disease
      were also more common among patients with NTM disease than controls (six out of
      30 versus none out of 61). This association between NTM disease and Aspergillus
      related lung disease remained significant after adjustment for confounding
      effects of age and lung function (adjusted odds ratio 5.1, 95% confidence
      interval 1.5-17.0). Patients with bronchiectasis and nontuberculous mycobacterial
      disease have a higher prevalence of coexisting Aspergillus-related lung disease
      than patients with bronchiectasis and without nontuberculous mycobacteria.
      Identification of Aspergillus-related lung disease is important as prognosis
      amongst undetected cases is invariably poor.

PMID- 16611652
TI  - The efficacy of bosentan in inoperable chronic thromboembolic pulmonary
      hypertension: a 1-year follow-up study.
AB  - The treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH)
      is pulmonary endarterectomy (PEA). However, many patients develop a severe
      progressive small vessel pulmonary arteriopathy that is inaccessible to surgical
      intervention and is associated with poor survival. The purpose of the present
      study was to evaluate the medium-term efficacy and safety of the dual endothelin
      receptor antagonist, bosentan, in inoperable CTEPH. Forty-seven patients with
      inoperable CTEPH (distal disease or persistent pulmonary hypertension following
      PEA) underwent evaluation after 1 yr of bosentan therapy. Outcomes included
      assessment of 6-min walk test (6MWT), haemodynamics and World Health Organization
      functional classification. Monitoring of serious adverse effects and changes in
      therapy was undertaken. Patients showed sustained improvements in 6MWT (49+/-8
      m), functional classification, cardiac index (+0.2+/-0.07 L.min(-1).m(-2)) and
      total pulmonary resistance (-139+/-42 dyn.s.cm(-5)). Those patients with
      persisting pulmonary hypertension following PEA showed the greatest improvement.
      One-yr survival was 96%, and bosentan was well tolerated with only one patient
      developing deranged liver function. Although all patients with chronic
      thromboembolic pulmonary hypertension should be considered for pulmonary
      endarterectomy, bosentan provides an alternative medical therapy to improve
      function and delay the progression of this devastating disease in those in whom
      surgery is not suitable.

PMID- 16611653
TI  - COPD is associated with increased mortality in patients with community-acquired
      pneumonia.
AB  - Patients with chronic obstructive pulmonary disease (COPD) who develop community
      acquired pneumonia (CAP) may experience worse clinical outcomes. However, COPD is
      not included as a distinct diagnosis in validated instruments that predict
      mortality in patients with CAP. The aim of the present study was to evaluate the
      impact of COPD as a comorbid condition on 30- and 90-day mortality in CAP
      patients. A retrospective observational study was conducted at two hospitals.
      Eligible patients had a discharge diagnosis and radiological confirmation of CAP.
      Among 744 patients with CAP, 215 had a comorbid diagnosis of COPD and 529 did not
      have COPD. The COPD group had a higher mean pneumonia severity index score (105+/
      32 versus 87+/-34) and were admitted to the intensive care unit more frequently
      (25 versus 18%). After adjusting for severity of disease and processes of care,
      CAP patients with COPD showed significantly higher 30- and 90-day mortality than
      non-COPD patients. Chronic obstructive pulmonary disease patients hospitalised
      with community-acquired pneumonia exhibited higher 30- and 90-day mortality than
      patients without chronic obstructive pulmonary disease. Chronic obstructive
      pulmonary disease should be evaluated for inclusion in community-acquired
      pneumonia prediction instruments.

PMID- 16611654
TI  - Global burden of COPD: systematic review and meta-analysis.
AB  - The aim of this study was to quantify the global prevalence of chronic
      obstructive pulmonary disease (COPD) by means of a systematic review and random
      effects meta-analysis. PubMed was searched for population-based prevalence
      estimates published during the period 1990-2004. Articles were included if they:
      1) provided total population or sex-specific estimates for COPD, chronic
      bronchitis and/or emphysema; and 2) gave method details sufficiently clearly to
      establish the sampling strategy, approach to diagnosis and diagnostic criteria.
      Of 67 accepted articles, 62 unique entries yielded 101 overall prevalence
      estimates from 28 different counties. The pooled prevalence of COPD was 7.6% from
      37 studies, of chronic bronchitis alone (38 studies) was 6.4% and of emphysema
      alone (eight studies) was 1.8%. The pooled prevalence from 26 spirometric
      estimates was 8.9%. The most common spirometric definitions used were those of
      the Global Initiative for Chronic Obstructive Lung Disease (13 estimates). There
      was significant heterogeneity, which was incompletely explained by subgroup
      analysis (e.g. age and smoking status). The prevalence of physiologically defined
      chronic obstructive pulmonary disease in adults aged > or =40 yrs is
      approximately 9-10%. There are important regional gaps, and methodological
      differences hinder interpretation of the available data. The efforts of the
      Global Initiative for Chronic Obstructive Lung Disease and similar groups should
      help to standardise chronic obstructive pulmonary disease prevalence measurement.

PMID- 16611655
TI  - High ICAM-1 gene expression in pulmonary fibroblasts of COPD patients: a
      reflection of an enhanced immunological function.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by destruction of
      extracellular matrix (ECM) in parenchymal areas, whereas the bronchial walls can
      show fibrosis. In addition, an extensive inflammatory process is observed. CD8+ T
      cells, located throughout the lung, and epithelial cells in centrally located
      airways, produce cytokines involved in the inflammatory process. These cytokines
      may influence the present fibroblasts, the key effectors in the defective ECM
      repair and maintenance in COPD. The current authors explored the effects of the
      cytokine microenvironment on cell-cell interaction gene expression in pulmonary
      fibroblasts of controls (n = 6), and Global Initiative for Chronic Obstructive
      Lung Disease stage II (n = 7) and stage IV (n = 7) COPD patients. The current
      authors simulated the in vivo microenvironment using supernatants of CD3/CD28
      stimulated CD8+ T-cells isolated from peripheral blood of COPD patients,
      supernatant of a bronchial-epithelial cell line, or a combination of both. The
      present data show that fibroblasts of chronic obstructive pulmonary disease
      patients display an altered response to the cytokine microenvironment, depending
      on both the disease stage and the central or peripheral location in the lung.
      Especially adhesion-related genes are upregulated in fibroblasts of chronic
      obstructive pulmonary disease patients, which can indicate a more pronounced role
      of fibroblasts in the inflammatory process in chronic obstructive pulmonary
      disease, possibly resulting in reduced function as effectors of extracellular
      matrix repair.

PMID- 16611656
TI  - Integrated care prevents hospitalisations for exacerbations in COPD patients.
AB  - Hospital admissions due to chronic obstructive pulmonary disease (COPD)
      exacerbations have a major impact on the disease evolution and costs. The current
      authors postulated that a simple and well-standardised, low-intensity integrated
      care intervention can be effective to prevent such hospitalisations. Therefore,
      155 exacerbated COPD patients (17% females) were recruited after hospital
      discharge from centres in Barcelona (Spain) and Leuven (Belgium). They were
      randomly assigned to either integrated care (IC; n = 65; age mean+/-sd 70+/-9
      yrs; forced expiratory volume in one second (FEV(1)) 1.1+/-0.5 L, 43% predicted)
      or usual care (UC; n = 90; age 72+/-9 yrs; FEV(1) 1.1+/-0.05 L, 41% pred). The IC
      intervention consisted of an individually tailored care plan upon discharge
      shared with the primary care team, as well as accessibility to a specialised
      nurse case manager through a web-based call centre. After 12 months' follow-up,
      IC showed a lower hospitalisation rate (1.5+/-2.6 versus 2.1+/-3.1) and a higher
      percentage of patients without re-admissions (49 versus 31%) than UC without
      differences in mortality (19 versus 16%, respectively). In conclusion, this trial
      demonstrates that a standardised integrated care intervention, based on shared
      care arrangements among different levels of the system with support of
      information technologies, effectively prevents hospitalisations for exacerbations
      in chronic obstructive pulmonary disease patients.

PMID- 16611657
TI  - Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic
      pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly
      disease with no effective treatment. The purpose of this randomised prospective
      multicentric study was to characterise the clinical effects of interferon gamma
      (IFN-gamma) 1b administered subcutaneously thrice weekly versus colchicine for 2
      yrs. This study had no pre-specified end-points. Fifty consecutive IPF patients
      were randomised. Patients with mild-to-moderate IPF were eligible for the study
      if they had histologically proven IPF, or, in the absence of surgical biopsy,
      fulfilled the European Respiratory Society/American Thoracic Society criteria. In
      the intent-to-treat population, five out of 32 (15.6%) IFN-gamma-1b patients and
      seven out of 18 (38.8%) colchicine patients died after a median follow-up period
      of 25 months Patients treated with IFN-gamma 1b showed a better outcome after 2
      yrs of therapy, and fewer symptoms, as assessed using the St George's Respiratory
      Questionnaire, after 12 months of therapy. Also, the IFN-gamma-1b group exhibited
      a higher forced vital capacity (percentage of the predicted value) after 24
      months of treatment. No significant differences were detected in resting arterial
      oxygen tension, total lung capacity (% pred), transfer factor of the lung for
      carbon monoxide (% pred) and high-resolution computed tomographic scoring between
      the two treatment groups. These data suggest that long-term treatment with
      interferon gamma 1b may improve survival and outcome in patients with mild-to
      moderate idiopathic pulmonary fibrosis. Further studies are needed to verify
      these results.

PMID- 16611658
TI  - Comparison of two commercial interferon-gamma assays for diagnosing Mycobacterium
      tuberculosis infection.
AB  - The clinical usefulness of ex vivo interferon-gamma assays may largely depend on
      the assay format and epidemiological status of tuberculosis (TB) in the region
      studied. From July 2004 to June 2005 a prospective comparison study was
      undertaken at a tertiary referral hospital in South Korea. The results of
      tuberculin skin tests (TST) and the commercially available QuantiFERON-TB Gold
      (QFT-G) and T SPOT-TB (SPOT) assays were compared in an intermediate TB-burden
      country. Of the 224 participants studied, results from all three tests (TST, QFT
      G, and SPOT) were available in 218; 87 with active TB and 131 at a low risk for
      TB. Using 10 mm as a cut-off for TST, SPOT sensitivity (96.6%) was significantly
      higher than that seen for TST (66.7%) and QFT-G (70.1%). QFT-G showed superior
      specificity over TST (91.6 versus 78.6%). Although the specificity of QFT-G was
      higher than that of SPOT (91.6 versus 84.7%), the difference was not
      statistically significant. Whilst some differences were found in the performance
      of the two commercialised interferon-gamma assays, they seemed to be superior in
      their detection of Mycobacterium tuberculosis infection compared with tuberculin
      skin tests. The most appropriate choice of interferon-gamma assay to use may
      depend on the clinical setting.

PMID- 16611659
TI  - Direct costs of three models for the screening of latent tuberculosis infection.
AB  - The aim of the present study was to compare the direct costs of three models for
      detection of latent tuberculosis infection (LTBI) in routine clinical practice in
      Switzerland. Comparison of the overall costs of screening for LTBI, including
      medical and radiological examination, and preventive treatment associated with
      three screening models was carried out. Model 1 relies only on the tuberculin
      skin test (TST) according to the current national guidelines, model 2 relies on T
      SPOT.TB (Oxford Immunotec, Oxford, UK) only and model 3 relies on TST followed by
      confirmation of positive results by T-SPOT.TB. Costs were taken directly from the
      clinic's figures. Clinical assumptions were based on the 267 patients who were
      referred to the clinic over the study period. Model 3 was found to be the most
      cost-effective. Using only the skin test (model 1) was the least cost-effective.
      If only one test for LTBI is to be used, then model 2 (using T-SPOT.TB only) is
      cheaper than using the TST (model 1). Screening for latent tuberculosis infection
      by tuberculin skin test followed by confirmation with T-SPOT.TB is less costly
      than screening with tuberculin skin test alone, as it allows a reduction in the
      number of people who receive preventive treatment. In groups with a high
      proportion of negative tuberculin skin tests, screening with T-SPOT.TB test only
      may be the most cost-effective.

PMID- 16611660
TI  - Static pressure-volume curves and body posture in severe chronic bronchitis.
AB  - Based on prior data, the current authors hypothesised that beneficial pronation
      effects on gas exchange and respiratory mechanics might be maximised in severely
      hyperinflated chronic bronchitis patients. The current authors also sought to
      elucidate underlying mechanisms and to determine whether pronation effects are
      reflected by postural changes in inspiratory pressure-volume (P-V) curve
      characteristics. A total of 16 mechanically ventilated patients (for 16-36 h)
      with chronic bronchitis exacerbation were studied in pre-prone semirecumbent
      (SREC), prone and post-prone SREC postures. Static respiratory system intrinsic
      positive end-expiratory pressure (PEEPi,rs) was >12 cmH2O. Haemodynamics,
      partitioned respiratory mechanics, gas exchange, and lung volumes were determined
      at zero external positive end-expiratory pressure. P-V curves were constructed
      from functional residual capacity. End-expiratory lung volume exceeded opening
      volume. Prone position versus pre-prone SREC resulted in 20% reduced pressure at
      the lower inflection point (LIP) and 17% increased volume at the upper inflection
      point of the lung P-V curve, improved lung mechanics and volumes, oxygenation,
      and carbon dioxide arterial tension (Pa,CO2). In multiple linear regression,
      postural decreases in PEEPi,rs and additional lung resistance independently
      predicted postural decreases in lung LIP pressure and Pa,CO2), respectively. In
      conclusion, in severely hyperinflated patients, pronation reduces lung lower
      inflection point pressure and increases lung upper inflection point volume.
      Pronation effects on ventilation homogeneity and carbon dioxide arterial tension
      are maximised, implying that pronation can be useful during early controlled
      ventilation.

PMID- 16611661
TI  - The use of recursive partitioning analysis grouping in patients with brain
      metastases from non-small-cell lung cancer.
AB  - BACKGROUND: This study evaluates the use of recursive partitioning analysis (RPA)
      grouping in an attempt to predict the survival probabilities in patients with
      brain metastases from non-small-cell lung cancer (NSCLC). METHODS: Seventy-two
      patients with brain metastases from NSCLC treated with radiation therapy were
      included in the study. Sixty-three patients were male and nine patients were
      female. Their median age was 57 years and their median Karnofsky performance
      status was 70. At the time of brain metastases, there was no evidence of the
      intrathoracic disease in 27 patients and the extrathoracic disease was limited to
      the intracranial disease in 42 patients. In accordance with RPA grouping, 12
      patients were in Group 1, 24 patients were in Group 2, and 36 patients were in
      Group 3. Radiation therapy was delivered to the whole brain at a dose of 30 Gy in
      10 fractions in most of the patients. RESULTS: The median survival time was 7
      months for Group 1, 5 months for Group 2 and 3 months for Group 3. The survival
      probability at 1 year was 50% for Group 1, 26% for Group 2 and 14% for Group 3.
      CONCLUSIONS: This study presents evidence supporting the use of RPA grouping in
      an attempt to predict the survival probabilities in patients with brain
      metastases from NSCLC.

PMID- 16611662
TI  - A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with
      solid malignancy: safety assessment based on the phase I data.
AB  - OBJECTIVE: We conducted a phase I study to investigate the safety of a weekly WT1
      tumor vaccine therapy in patients with solid tumors that had been refractory to
      all other anti-cancer therapies. METHODS: Skin-test-negative patients were
      intradermally injected weekly for 12 weeks with 3.0 mg of an HLA-A*2402
      restricted modified 9-mer WT1 peptide emulsified in Montanide ISA51 adjuvant. We
      estimated the Bayesian posterior probability of the occurrence of grade 3 or 4
      toxicity when receiving the weekly WT1 vaccination. This analysis provided the
      basis for making a decision to terminate the phase I study and switch to phase
      II. Moreover, we performed an exploratory assessment of the anti-tumor effects of
      WT1 treatment. RESULTS: Ten patients received 114 vaccinations with WT1 on a
      weekly schedule. No grade 3 or 4 toxicities were observed. Based on the Bayesian
      approach, it was highly likely that the probability of grade 3 or 4 toxicity was
      below 20% (the posterior probability = 0.914). Fifteen grade 2 and two grade 1
      toxicities were observed; all of these incidents, however, were determined by the
      Independent Data and Safety Monitoring Committee to be unrelated to the WT1
      treatment. One patient exhibited a partial response; five additional patients had
      stable disease while receiving weekly WT1 treatment. CONCLUSION: This paper
      confirms that the potential toxicities of the treatment schedule of weekly WT1
      vaccination are acceptable and suggested a potential anti-tumor effect.
      Consequently, we validated the decision to continue to the phase II trial.

PMID- 16611663
TI  - Doxorubicin-conjugated anti-midkine monoclonal antibody as a potential anti-tumor
      drug.
AB  - BACKGROUND: Midkine is a heparin-binding growth factor preferentially expressed
      in tumor cells. The present study was performed to utilize anti-midkine antibody
      for tumor therapy. METHODS: A monoclonal antibody to midkine was raised by
      immunizing mice deficient in the midkine gene. The binding site of the antibody
      was studied by using N-terminal half and C-terminal half of midkine, both of
      which were chemically synthesized. Doxorubicin (DOX)-conjugate of the antibody
      was produced by chemical conjugation. The effects of the antibody and the
      conjugate on cell growth were examined using a midkine-secreting tumor cell, i.e.
      human hepatocellular carcinoma cell (HepG2). RESULTS: The monoclonal antibody
      bound to the N-terminal half of midkine. The antibody did not inhibit the growth
      of HepG2 cells probably because the active domain of midkine is in the C-terminal
      half. We produced the antibody conjugated with DOX with the hope that the
      conjugate would be internalized accompanied with midkine. Indeed, the antibody
      DOX conjugate significantly inhibited the growth of HepG2 cells compared with DOX
      conjugated control IgG. CONCLUSION: The result raises the possibility of using
      anti-midkine antibody conjugated with DOX for cancer therapy.

PMID- 16611664
TI  - Association of anthropometric measures with the presence and progression of
      benign prostatic hyperplasia.
AB  - The authors investigated the association of anthropometric measures with the
      presence and progression of components of benign prostatic hyperplasia (BPH) and
      a clinical outcome of BPH in a cohort of healthy, Caucasian men aged 40-79 years
      that was randomly selected from the Olmsted County, Minnesota, population
      beginning in 1990. Exclusionary criteria included prostate or bladder surgery,
      urethral surgery or stricture, or medical or other neurologic conditions that
      could affect normal urinary function. Height, weight, and waist and hip
      circumferences were measured. Components of BPH, including American Urological
      Association Symptom Index scores, peak urinary flow rate, and prostate volume,
      were assessed on a randomly selected subsample. Acute urinary retention was
      assessed through review of community medical records. There were few significant
      associations of anthropometric measures with the presence or progression of
      components of BPH or clinical outcome of BPH, and there were no instances where
      the point estimates for the BPH components suggested a dose-response effect. The
      authors conclude that anthropometric measures are not significantly associated
      with the presence or progression of BPH as measured by American Urological
      Association Symptom Index scores, peak urinary flow rate, prostate volume, or
      acute urinary retention. These data provide no evidence of a consistent
      significant relation between anthropometric measures and BPH.

PMID- 16611665
TI  - The long-term effect of insomnia on work disability: the HUNT-2 historical cohort
      study.
AB  - Chronic insomnia is common in the general population. Its effect on functioning
      and disability is usually attributed to an underlying condition, so the diagnosis
      of insomnia does not qualify for award of a disability pension in the United
      States or Europe. The aim of this study was to investigate whether insomnia,
      defined according to the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, contributed to long-term work disability. Using a historical
      cohort design, the authors gathered baseline data from a population-based
      Norwegian health study of 37,308 working-age people not claiming a disability
      pension through 1995-1997. The outcome was subsequent award of a disability
      pension (18-48 months after the health screening) as registered by the National
      Insurance Administration. Insomnia was a strong predictor of subsequent permanent
      work disability (adjusted odds ratio=3.90, 95% confidence interval: 3.20, 4.76).
      Sociodemographic and shift-work characteristics had little confounding effect
      (adjusted odds ratio=3.69, 95% confidence interval: 3.00, 4.53), and this
      association remained significant after adjustment for psychiatric and physical
      morbidity and for health-related behaviors (adjusted odds ratio=1.75, 95%
      confidence interval: 1.40, 2.20). This study suggests that insomnia should
      receive increased attention as a robust predictor of subsequent work disability.

PMID- 16611666
TI  - Combining risk estimates from observational studies with different exposure
      cutpoints: a meta-analysis on body mass index and diabetes type 2.
AB  - Studies on a dose-response relation often report separate relative risks for
      several risk classes compared with a referent class. When performing a meta
      analysis of such studies, one has to convert these relative risks into an overall
      relative risk for a continuous effect. Apart from taking the dependence between
      separate relative risks into account, this implies assigning an exposure level to
      each risk factor class and allowing for the nonlinearity of the dose-response
      relation. The authors describe a relatively simple method solving these problems.
      As an illustration, they applied this method in a meta-analysis of the
      association between body mass index and diabetes type 2, restricted to results of
      follow-up studies (n=31). Results were compared with a more ad hoc method of
      assigning exposure levels and with a method in which the nonlinearity of the dose
      response method was not taken into account. Differences with the ad hoc method
      were larger in studies with fewer categories. Not incorporating the nonlinearity
      of the dose response leads to an overestimation of the pooled relative risk, but
      this bias is relatively small.

PMID- 16611667
TI  - Plasma sphingomyelin and subclinical atherosclerosis: findings from the multi
      ethnic study of atherosclerosis.
AB  - Plasma sphingomyelin has been shown to be an independent risk factor for coronary
      heart disease, but the relation of plasma sphingomyelin to earlier, subclinical
      atherosclerotic disease has not been reported. The authors examined the
      association between plasma sphingomyelin and three measures of subclinical
      cardiovascular disease (carotid intimal-medial wall thickness, ankle-arm blood
      pressure index, and Agatston coronary artery calcium score) among 6,814 middle
      aged, asymptomatic adults in the Multi-Ethnic Study of Atherosclerosis, which was
      initiated in 2000. The sphingomyelin level was positively correlated with lipids
      and the Framingham risk score (p < 0.01 for both), and the mean level was higher
      in women than men (50 (standard deviation (SD), 16) vs. 45 (SD, 15) mg/dl) (p <
      0.01) and higher in never versus current smokers (49 (SD, 16) vs. 45 (SD, 17)
      mg/dl) (p < 0.01). Women with sphingomyelin levels of 60 or more mg/dl had more
      severe subclinical disease by all three measures than did the referent group with
      sphingomyelin levels of 39 or less mg/dl, although associations were not
      significant after multivariate adjustment for standard cardiovascular disease
      risk factors. Men with sphingomyelin levels of 60 or more mg/dl versus those with
      sphingomyelin levels of 39 or less mg/dl had higher calcium scores (135 vs. 99
      Agatston units) (p = 0.01). These observations are consistent with the hypothesis
      that plasma sphingomyelin is in the biologic pathway that mediates the risk for
      subclinical disease attributable to standard cardiovascular disease risk factors.

PMID- 16611668
TI  - Pesticides associated with wheeze among commercial pesticide applicators in the
      Agricultural Health Study.
AB  - Pesticides are potential risk factors for respiratory disease among farmers, but
      farmers are also exposed to other respiratory toxicants. To explore the
      association of pesticides with wheeze in a population without other farming
      exposures, the authors analyzed data from 2,255 Iowa commercial pesticide
      applicators enrolled in the Agricultural Health Study. Controlling for age,
      smoking status, asthma and atopy history, and body mass index, the authors
      calculated odds ratios for the relationship between wheeze and 36 individual
      pesticides participants had used during the year before enrollment (1993-1997).
      Eight of 16 herbicides were associated with wheeze in single-agent models;
      however, the risk was almost exclusively associated with the herbicide
      chlorimuron-ethyl (odds ratio (OR) = 1.62, 95% confidence interval (CI): 1.25,
      2.10). Inclusion of chlorimuron-ethyl in models for the other herbicides
      virtually eliminated the associations. The odds ratios for four organophosphate
      insecticides (terbufos, fonofos, chlorpyrifos, and phorate) were elevated when
      these chemicals were modeled individually and remained elevated, though
      attenuated somewhat, when chlorimuron-ethyl was included. The association for
      dichlorvos, another organophosphate insecticide, was not attenuated by
      chlorimuron-ethyl (OR = 2.48, 95% CI: 1.08, 5.66). Dose-response trends were
      observed for chlorimuron-ethyl, chlorpyrifos, and phorate; the strongest odds
      ratio was for applying chlorpyrifos on more than 40 days per year (OR = 2.40, 95%
      CI: 1.24, 4.65). These results add to the emerging literature linking
      organophosphate insecticides and respiratory health and suggest a role for
      chlorimuron-ethyl.

PMID- 16611669
TI  - Prognostic significance of the change in glucose level in the first 24 h after
      acute myocardial infarction: results from the CARDINAL study.
AB  - AIMS: In acute myocardial infarction (AMI), baseline hyperglycaemia predicts
      adverse outcomes, but the relation between subsequent change in glucose levels
      and outcomes is unclear. We evaluated the prognostic significance of baseline
      glucose and the change in glucose in the first 24 h following AMI. METHODS AND
      RESULTS: We analysed 1469 AMI patients with baseline and 24 h glucose data from
      the CARDINAL trial database. Baseline glucose and the 24 h change in glucose (24
      h glucose level subtracted from baseline glucose) were included in multivariable
      models for 30- and 180-day mortality. By 30 and 180 days, respectively, 45 and 74
      patients had died. In the multivariable 30-day mortality model, neither baseline
      glucose nor the 24 h change in glucose predicted mortality in diabetic patients
      (n=250). However, in nondiabetic patients (n=1219), higher baseline glucose
      predicted higher mortality [hazard ratio (HR) 1.12, 95% confidence interval (CI)
      1.04-1.20, per 0.6 mmol/L increase], and a greater 24 h change in glucose
      predicted lower mortality (HR 0.91, 95% CI 0.86-0.96, for every 0.6 mmol/L drop
      in glucose in the first 24 h) at 30 days. Baseline glucose and the 24 h change in
      glucose remained significant multivariable mortality predictors at 180 days in
      nondiabetic patients. CONCLUSION: Both higher baseline glucose and the failure of
      glucose levels to decrease in the first 24 h after AMI predict higher mortality
      in nondiabetic patients.

PMID- 16611670
TI  - Chronic kidney disease and risk of incident myocardial infarction and all-cause
      and cardiovascular disease mortality in middle-aged men and women from the
      general population.
AB  - AIMS: Chronic kidney disease (CKD) was found to be an independent risk factor for
      all-cause mortality as well as adverse cardiovascular disease (CVD) events in
      high-risk populations. Findings from population-based studies are scarce and
      inconsistent. We investigated the gender-specific association of CKD with all
      cause mortality, cardiovascular mortality, and incident myocardial infarction
      (MI) in a population-based cohort. METHODS AND RESULTS: The study was based on
      3860 men and 3674 women (aged 45-74 years) who participated in one of the three
      MONICA Augsburg surveys between 1984 and 1995. CKD was defined by an estimated
      glomerular filtration rate between 15 and 59 mL/min/1.73 m(2). Hazard ratios
      (HRs) were estimated from Cox proportional hazard models. In this study, 890
      total deaths, 400 CVD deaths, and 321 incident MIs occurred in men up to 31
      December 2002; the corresponding numbers in women were 442, 187, and 102. In
      multivariable analyses, the HR for women with CKD compared to women with
      preserved renal function was significant for incident MI [HR 1.67; 95% confidence
      interval (CI) 1.07-2.61] and CVD mortality (HR 1.60; 95% CI 1.17-2.18). In men,
      CKD was also significantly associated with incident MI (HR 1.51; 95% CI 1.09
      2.10) and CVD mortality (HR 1.48; 95% CI 1.15-1.92) after adjustment for common
      CVD risk factors. In contrast, men and women with CKD had no significant
      increased risk of all-cause mortality. CONCLUSION: CKD was strongly associated
      with an increased risk of incident MI and CVD mortality independent from common
      cardiovascular risk factors in men and women from the general population.

PMID- 16611671
TI  - Uric acid and inflammatory markers.
AB  - AIMS: The role of uric acid (UA) in the process of atherosclerosis and
      atherotrombosis is controversial. Epidemiological studies have recently shown
      that UA may be a risk factor for cardiovascular diseases and a negative
      prognostic marker for mortality in subjects with pre-existing heart failure.
      METHODS AND RESULTS: We evaluate a relationship between UA levels and several
      inflammatory markers in 957 subjects, free of severe renal failure, from a
      representative Italian cohort of persons aged 65-95. Plasma levels of UA and
      white blood cell (WBC) and neutrophil count, C-reactive protein, interleukin-1
      receptor antagonist (IL-1ra), interleukin-6 (IL-6), soluble IL-6 receptor (sIL
      6r), interleukin-18 (IL-18), and tumor necrosis factor-alpha (TNF-alpha) were
      measured. Complete information on potential confounders was collected using
      standard methods. WBC (P=0.0001), neutrophils (P<0.0001), C-reactive protein
      (P<0.0001), IL-1ra (P<0.0001), IL-6 (P=0.0004), sIL-6r (P=0.002), IL-18
      (P<0.0001), TNF-alpha (P=0.0008), and the percentage of subjects with abnormally
      high levels of C-reactive protein (P=0.004) and IL-6 (P=<0.0001) were
      significantly higher across UA quintiles. After adjustment for age, sex,
      behaviour- and disease-related confounders, results were virtually unchanged. In
      subjects with UA within the normal range, UA was significantly and independently
      associated with neutrophils count, C-reactive protein, IL-6, IL-1ra, IL-18, and
      TNF-alpha, whereas non-significant trends were observed for WBC (P=0.1) and sIL
      6r (P=0.2). CONCLUSION: A positive and significant association between UA and
      several inflammatory markers was found in a large population-based sample of
      older persons and in a sub-sample of participants with normal UA. Accordingly,
      the prevalence of abnormally high levels of C-reactive protein and IL-6 increased
      significantly across UA quintiles.

PMID- 16611672
TI  - Anthracycline cardiotoxicity.

PMID- 16611673
TI  - New susceptibility locus for hypertension on chromosome 8q by efficient pedigree
      breaking in an Italian isolate.
AB  - Essential hypertension (EH) affects a large proportion of the adult population in
      Western countries and is a major risk factor for cardiovascular diseases. EH is a
      multifactorial disease with a complex genetic component. To tackle the complexity
      of this genetic component, we have initiated a study of Campora, an isolated
      village in South Italy. A random sample of 389 adults was genotyped for a very
      dense microsatellite genome scan and phenotyped for EH. Of this sample, 173
      affected individuals were all related through a 2,180-member pedigree and could
      be integrated within a linkage analysis. The complexity of the pedigree prevented
      its direct use for a non-parametric linkage (NPL) analysis. Therefore, the method
      proposed by Falchi et al. [2004, Am. J. Hum. Genet., 75, 1015-1031] was used for
      automatic pedigree-breaking. We identified a new locus for EH on chromosome 8q22
      23 and detected linkage with two known loci for EH: 1q42-43 and 4p16. Simulations
      showed that the linkage with 8q22-23 is highly genome-wide significant, even when
      accounting for the breaking of the pedigree. An extension to qualitative traits
      of another pedigree-breaking approach [Pankratz et al., 2001, Genet. Epidemiol.,
      21 (Suppl. 1), S258-S263] also detected a significant linkage on 8q22-23 using a
      remarkably different set of sub-pedigrees and helped to refine the location of
      the linkage signal. This work both identifies a new locus strongly linked to
      hypertension and shows that the power of linkage analysis can be improved by the
      appropriate use of efficient pedigree-breaking strategies.

PMID- 16611674
TI  - A haplotype spanning two genes, ELN and LIMK1, decreases their transcripts and
      confers susceptibility to intracranial aneurysms.
AB  - The rupture of an intracranial aneurysm (IA) results in subarachnoid hemorrhage,
      a catastrophic neurological condition with high morbidity and mortality.
      Following-up on our previous genome-wide linkage study in Japanese population, we
      extensively analyzed a 4.6 Mb linkage region around D7S2472 on 7q11 by genotyping
      168 single nucleotide polymorphisms (SNPs). SNP association and window scan
      haplotype-based association studies revealed a susceptibility locus for IA on a
      single LD block covering the 3'-untranslated region (3'-UTR) of ELN and the
      entire region of LIMK1. An association study with 404 IA patients and 458 non-IA
      controls revealed that the ELN 3'-UTR G(+659)C SNP has the strongest association
      to IA (P=0.000002) and constitutes a tag-SNP for an at-risk haplotype, which
      contains two functional SNPs, the ELN 3'-UTR (+502) A insertion and the LIMK1
      promoter C(-187)T SNP. These allelic and haplotype-based associations were
      confirmed in a Korean population. Ex vivo and in vitro analyses demonstrate that
      the functional impact of both SNPs is the decrease of transcript levels, either
      through accelerated ELN mRNA degradation or through decreased LIMK1 promoter
      activity. Elastin and LIMK1 protein are involved in the same actin
      depolymerization signaling pathway; therefore, these lines of evidence suggest a
      combined effect of the SNPs in the at-risk haplotype possibly by weakening the
      vascular wall and promoting the development of IA.

PMID- 16611676
TI  - Is the diagnosis of chronic kidney disease missed in diabetic women?

PMID- 16611677
TI  - The search for a link between inflammation and hypertension--contribution from
      Bartter's/Gitelman's syndromes.

PMID- 16611675
TI  - A quantitative trait locus (QTL) on chromosome 6q influences birth weight in two
      independent family studies.
AB  - Low birth weight is an important cause of infant mortality and morbidity
      worldwide. Birth weight has been shown to be inversely correlated with adult
      complex diseases such as obesity, type-2 diabetes and cardiovascular disease.
      However, little is known about the genetic factors influencing variation in birth
      weight and its association with diseases that occur in later life. We, therefore,
      have performed a genome-wide search to identify genes that influence birth weight
      in Mexican-Americans using the data from the San Antonio Family Birth Weight
      Study participants (n=840). Heritability of birth weight was estimated as 72.0+/
      8.4% (P<0.0001) after adjusting for the effects of sex and term. Multipoint
      linkage analysis yielded the strongest evidence for linkage of birth weight
      (LOD=3.7) between the markers D6S1053 and D6S1031 on chromosome 6q. This finding
      has been replicated (LOD=2.3) in an independent European-American population.
      Together, these findings provide substantial evidence (LOD(adj)=4.3) for a major
      locus influencing variation in birth weight. This region harbors positional
      candidate genes such as chorionic gonadotropin, alpha chain; collagen, type XIX,
      alpha-1; and protein-tyrosine phosphatase, type 4A, 1 that may play a role in
      fetal growth and development. In addition, potential evidence for linkage
      (LOD>or=1.2) was found on chromosomes 1q, 2q, 3q, 4q, 9p, 19p and 19q with LODs
      ranging from 1.3 to 2.7. Thus, we have found strong evidence for a major gene on
      chromosome 6q that influences variation in birth weight in both Mexican- and
      European-Americans.

PMID- 16611678
TI  - Evaluation of cardiac function in the dialysis patient--a primer for the non
      expert.

PMID- 16611679
TI  - Ciprofloxacin crystal nephropathy--a 'new' cause of acute renal failure.

PMID- 16611680
TI  - Effect of L-carnitine administration on erythrocyte survival in haemodialysis
      patients.

PMID- 16611681
TI  - Dialysis dose (Kt/V) and clearance variation sensitivity using measurement of
      ultraviolet-absorbance (on-line), blood urea, dialysate urea and ionic
      dialysance.
AB  - BACKGROUND: An on-line monitoring system for dialysis dose calculations could
      make it possible to provide an adequate dialysis dose that is consistently given
      to haemodialysis (HD) patients. The aim of this study was to compare dialysis
      dose (Kt/V) using four different methods and their sensitiveness to a reduction
      in clearance. METHODS: Six patients were monitored on-line with ultraviolet (UV)
      absorbance at a wavelength of 297 nm in three consecutive dialysis sessions
      during 1 week. During the last treatment, the clearance was reduced by
      approximately 25% by decreasing the blood flow. For the determination of UV
      absorbance, a spectrophotometer was connected to the fluid outlet of the dialysis
      machine with all spent dialysate passing through a flow cuvette. The equilibrated
      Kt/V (eKt/V) estimated by UV-absorbance was compared with eKt/V from the ionic
      dialysance method using the on-line clearance monitor (OCM) and the appurtenant
      software dose-calculation tool DCTool (Fresenius Medical Care, Germany), eKt/V
      calculated from the dialysate-urea slope and with eKt/V from pre- and post
      dialysis blood-urea samples as reference. RESULTS: The study demonstrates that
      the sensitiveness to clearance reduction is similar in the four methods compared
      for eKt/V. When the different methods were compared, the mean eKt/V of UV
      absorbance was 1.21 +/- 0.20, blood 1.30 +/- 0.21, dialysate 1.32 +/- 0.21 and
      OCM (using the DCTool) 1.31 +/- 0.21. The standard deviation was of the same
      magnitude. CONCLUSION: The UV-method gives a similar response to clearance
      reduction compared with the other methods when comparing dialysis dose. The high
      sampling rate by continuous monitoring of UV-absorbance allows evaluation of the
      clearance process during dialysis and gives immediate feedback to on-line
      adjustments.

PMID- 16611682
TI  - A randomized trial of saline hydration to prevent contrast nephropathy in chronic
      renal failure patients.
AB  - BACKGROUND: Contrast nephropathy (CN) is a common cause of renal dysfunction that
      may be prevented by saline hydration and by drugs such as theophylline or
      furosemide. Whether oral saline hydration is as efficient as intravenous saline
      hydration is unknown. The preventive efficacy of theophylline and furosemide for
      CN remains controversial. The purpose of the current study was to evaluate the
      efficacy of oral saline hydration and of intravenous saline hydration plus
      theophylline or furosemide for the prevention of CN. METHODS: We prospectively
      studied 312 patients with chronic renal failure (serum creatinine 201+/-81
      micromol/l, Cockcroft clearance 37+/-12 ml/min/1.73 m(2)), who were undergoing
      various radiological procedures with a non-ionic, low osmolality contrast agent.
      Patients were randomly assigned to four arms. In arm A, patients received 1 g/10
      kg of body weight/day of sodium chloride per os for 2 days before the procedure.
      In arm B, patients received 0.9% saline intravenously at a rate of 15 ml/kg for 6
      h before the procedure. In arm C, patients received the same saline hydration as
      in arm B plus 5 mg/kg theophylline per os in one dose 1 h before the procedure.
      In arm D, patients received the same saline hydration as in arm B plus 3 mg/kg of
      furosemide intravenously just after the procedure. RESULTS: Patients were well
      matched with no significant differences at baseline in any measured parameters.
      Acute renal failure, defined as an increase in serum creatinine of 44 micromol/l
      (0.5 mg/dl), occurred in 27 out of 312 patients (8.7%). There was no significant
      difference between the rate of renal failure in the different arms of the study:
      five out of 76 (6.6%) in arm A, four out of 77 (5.2%) in arm B, six out of 80
      (7.5%) in arm C and 12 out of 79 (15.2%) in arm D. No patient had fluid overload
      or a significant increase in blood pressure in the 2 days following the
      radiological procedure. The independent predictors of CN were diabetes mellitus,
      high baseline serum creatinine and high systolic blood pressure. CONCLUSIONS:
      Oral saline hydration was as efficient as intravenous saline hydration for the
      prevention of CN in patients with stage 3 renal diseases. Furosemide and
      theophylline were not protective.

PMID- 16611683
TI  - Mannose-binding lectin level and polymorphism in patients on long-term peritoneal
      dialysis--level of serum mannose binding lectin with end-stage renal disease.

PMID- 16611684
TI  - Do sleep disorders start in dialysis or in early chronic kidney disease?

PMID- 16611685
TI  - Integrin-linked kinase acts as a pro-survival factor against high glucose
      associated osmotic stress in human mesangial cells.
AB  - BACKGROUND: Integrin-linked kinase (ILK) is a protein that plays an important
      role in extracellular matrix-mediated signalling. Recent studies implicated ILK
      dysregulation in the development of diabetic nephropathy. However, little is
      known about the significance of ILK up-regulation in response to high glucose in
      mesangial cells. METHODS: The ILK messenger (m)RNA and protein expression in
      human mesangial cells were analysed with quantitative real-time polymerase chain
      reaction (PCR) and western blotting after exposure to either 100, 200, or 500
      mg/dl glucose, or 100 mg/dl glucose + 400 mg/dl mannitol. Activation of protein
      Kinase B (PKB)/Akt was also determined by western blot analysis. Cells were
      transfected with ILK siRNA to determine the effects of ILK knockdown on PKB/Akt
      activation and cell death following treatment with high glucose or mannitol.
      RESULTS: High concentrations of glucose or mannitol for three days significantly
      up-regulated ILK mRNA and protein expression (P < 0.05 vs 100 mg/dl glucose). In
      contrast, ILK expression in cells exposed to the same conditions for seven days
      was unaffected. The time course of PKB/Akt phosphorylation was similar to that of
      ILK protein expression. The siRNA-mediated down-regulation of ILK expression
      inhibited the elevation of PKB/Akt phosphorylation induced by high glucose
      treatment. Furthermore, the inhibition of ILK expression promoted high glucose-
      or mannitol-induced apoptosis. CONCLUSION: The ILK may act as a pro-survival
      factor and play a role in protecting mesangial cells from hyperglycaemic osmotic
      stress.

PMID- 16611686
TI  - Quality of life in children with chronic kidney disease-patient and caregiver
      assessments.
AB  - BACKGROUND: Children with chronic kidney disease (CKD) require strict dietary and
      lifestyle modifications, however, there is little information on their quality of
      life. Our objective was to compare health-related quality of life (HRQOL) in
      children with different stages of CKD to each other and to a control population.
      METHODS: A cross-sectional assessment of HRQOL for physical, emotional, social
      and school domains was performed using the PedsQL Generic Core Scale. Data were
      collected from 20 children with chronic renal insufficiency (CRI; creatinine >
      200 micromol/l), 12 on maintenance haemodialysis or peritoneal dialysis (DIAL)
      and 27 with renal transplants (TX). Caregiver proxy reports were obtained for CRI
      (n = 20), DIAL (n = 17) and TX (n = 21). Between-group differences were assessed
      with ANOVA for the CKD groups; t-tests compared our CKD samples with controls.
      RESULTS: Children with CKD scored lower than the controls in all subscales,
      however, only TX compared with controls was significant (P < 0.02). DIAL children
      scored equal to or higher than the TX group in all domains. Analysis of
      covariance with number of medications as covariate yielded a significant result
      for the physical subscale (F = 8.95, df = 3, 53, P = 0.004). Proxy caregiver
      scores were lower than patient scores in all four domains. CONCLUSIONS: Children
      with CKD rate their HRQOL lower than the healthy controls do. It may be
      reassuring to caregivers that children on dialysis rate their HRQOL higher than
      would be expected. However, it is of some concern that caregiver perception of
      improved HRQOL following transplantation was not shared by their children in the
      present study.

PMID- 16611687
TI  - Tracing the first waves of lymphopoiesis in mice.
AB  - RAG1/GFP knock-in mice were used to precisely chart the emergence and expansion
      of cells that give rise to the immune system. Lymphopoietic cells detectable in
      stromal co-cultures arose as early as E8.5, i.e. prior to establishment of the
      circulation within the paraaortic splanchnopleura (P-Sp). These cells were Tie2+
      RAG1- CD34(Lo/-) Kit+ CD41-. While yolk sac (YS) also contained lymphopoietic
      cells after E9.5, CD41+ YS cells from < or =25-somite embryos produced myelo
      erythroid cells but no lymphocytes. Notch receptor signaling directed P-Sp cells
      to T lymphocytes but did not confer lymphopoietic potential on YS cells. Thus,
      definitive hematopoiesis arises in at least two independent sites that differ in
      lymphopoietic potential. Expression of RAG1, the earliest known lymphoid event,
      first occurred around E10.5 within the embryos. RAG1/GFP+ cells appeared in the
      liver at E11.0 and progenitors with B and/or T lineage potential were enumerated
      at subsequent developmental stages.

PMID- 16611688
TI  - Stabilization of beta-catenin impacts pancreas growth.
AB  - A recent study has shown that deletion of beta-catenin within the pancreatic
      epithelium results in a loss of pancreas mass. Here, we show that ectopic
      stabilization of beta-catenin within mouse pancreatic epithelium can have
      divergent effects on both organ formation and growth. Robust stabilization of
      beta-catenin during early organogenesis drives changes in hedgehog and Fgf10
      signaling and induces a loss of Pdx1 expression in early pancreatic progenitor
      cells. Together, these perturbations in early pancreatic specification culminate
      in a severe reduction of pancreas mass and postnatal lethality. By contrast,
      inducing the stabilized form of beta-catenin at a later time point in pancreas
      development causes enhanced proliferation that results in a dramatic increase in
      pancreas organ size. Taken together, these data suggest a previously
      unappreciated temporal/spatial role for beta-catenin signaling in the regulation
      of pancreas organ growth.

PMID- 16611689
TI  - C. elegans dystroglycan DGN-1 functions in epithelia and neurons, but not muscle,
      and independently of dystrophin.
AB  - The C. elegans dystroglycan (DG) homolog DGN-1 is expressed in epithelia and
      neurons, and localizes to basement membrane (BM) surfaces. Unlike vertebrate DG,
      DGN-1 is not expressed in muscle or required for muscle function. dgn-1 null
      mutants are viable but sterile owing to severe disorganization of the somatic
      gonad epithelium, and show defects in vulval and excretory cell epithelia and in
      motoneuron axon guidance. The defects resemble those of epi-1 laminin alphaB
      mutants, suggesting that DGN-1 serves as a receptor for laminin. dgn-1(0)/+
      animals are fertile but show gonad migration defects in addition to the defects
      seen in homozygotes, indicating that DGN-1 function is dosage sensitive.
      Phenotypic analyses show that DGN-1 and dystrophin-associated protein complex
      (DAPC) components have distinct and independent functions, in contrast to the
      situation in vertebrate muscle. The DAPC-independent functions of DGN-1 in
      epithelia and neurons suggest that vertebrate DG may also act independently of
      dystrophin/utrophin in non-muscle tissues.

PMID- 16611690
TI  - Diverse gap junctions modulate distinct mechanisms for fiber cell formation
      during lens development and cataractogenesis.
AB  - Different mutations of alpha3 connexin (Cx46 or Gja8) and alpha8 connexin (Cx50
      or Gja8), subunits of lens gap junction channels, cause a variety of cataracts
      via unknown mechanisms. We identified a dominant cataractous mouse line (L1),
      caused by a missense alpha8 connexin mutation that resulted in the expression of
      alpha8-S50P mutant proteins. Histology studies showed that primary lens fiber
      cells failed to fully elongate in heterozygous alpha8(S50P/+) embryonic lenses,
      but not in homozygous alpha8(S50P/S50P), alpha8-/- and alpha3-/- alpha8-/- mutant
      embryonic lenses. We hypothesized that alpha8-S50P mutant subunits interacted
      with wild-type alpha3 or alpha8, or with both subunits to affect fiber cell
      formation. We found that the combination of mutant alpha8-S50P and wild-type
      alpha8 subunits specifically inhibited the elongation of primary fiber cells,
      while the combination of alpha8-S50P and wild-type alpha3 subunits disrupted the
      formation of secondary fiber cells. Thus, this work provides the first in vivo
      evidence that distinct mechanisms, modulated by diverse gap junctions, control
      the formation of primary and secondary fiber cells during lens development. This
      explains why and how different connexin mutations lead to a variety of cataracts.
      The principle of this explanation can also be applied to mutations of other
      connexin isoforms that cause different diseases in other organs.

PMID- 16611691
TI  - vps25 mosaics display non-autonomous cell survival and overgrowth, and autonomous
      apoptosis.
AB  - Appropriate cell-cell signaling is crucial for proper tissue homeostasis. Protein
      sorting of cell surface receptors at the early endosome is important for both the
      delivery of the signal and the inactivation of the receptor, and its alteration
      can cause malignancies including cancer. In a genetic screen for suppressors of
      the pro-apoptotic gene hid in Drosophila, we identified two alleles of vps25, a
      component of the ESCRT machinery required for protein sorting at the early
      endosome. Paradoxically, although vps25 mosaics were identified as suppressors of
      hid-induced apoptosis, vps25 mutant cells die. However, we provide evidence that
      a non-autonomous increase of Diap1 protein levels, an inhibitor of apoptosis,
      accounts for the suppression of hid. Furthermore, before they die, vps25 mutant
      clones trigger non-autonomous proliferation through a failure to downregulate
      Notch signaling, which activates the mitogenic JAK/STAT pathway. Hid and JNK
      contribute to apoptosis of vps25 mutant cells. Inhibition of cell death in vps25
      clones causes dramatic overgrowth phenotypes. In addition, Hippo signaling is
      increased in vps25 clones, and hippo mutants block apoptosis in vps25 clones. In
      summary, the phenotypic analysis of vps25 mutants highlights the importance of
      receptor downregulation by endosomal protein sorting for appropriate tissue
      homeostasis, and may serve as a model for human cancer.

PMID- 16611692
TI  - Classic cadherins regulate tangential migration of precerebellar neurons in the
      caudal hindbrain.
AB  - Classic cadherins are calcium dependent homophilic cell adhesion molecules that
      play a key role in developmental processes such as morphogenesis,
      compartmentalization and maintenance of a tissue. They also play important roles
      in development and function of the nervous system. Although classic cadherins
      have been shown to be involved in the migration of non-neuronal cells, little is
      known about their role in neuronal migration. Here, we show that classic
      cadherins are essential for the migration of precerebellar neurons. In situ
      hybridization analysis shows that at least four classic cadherins, cadherin 6
      (Cad6), cadherin 8 (Cad8), cadherin11 (Cad11) and N-cadherin (Ncad), are
      expressed in the migratory streams of lateral reticular nucleus and external
      cuneate nucleus (LRN/ECN) neurons. Functional analysis performed by
      electroporation of cadherin constructs into the hindbrain indicates requirement
      for cadherins in the migration of LRN/ECN neurons both in vitro and in vivo.
      While overexpression of full-length classic cadherins, NCAD and CAD11, has no
      effect on LRN/ECN neuron migration, overexpression of two dominant negative (DN)
      constructs, membrane-bound form and cytoplasmic form, slows it down. Introduction
      of a DN construct does not alter some characteristics of LRN/ECN cells as
      indicated by a molecular marker, TAG1, and their responsiveness to chemotropic
      activity of the floor plate (FP). These results suggest that classic cadherins
      contribute to contact-dependent mechanisms of precerebellar neuron migration
      probably via their adhesive property.

PMID- 16611693
TI  - Differentiation of cerebellar cell identities in absence of Fgf signalling in
      zebrafish Otx morphants.
AB  - Although the secreted molecule Fgf8 is a key player of the isthmic organiser
      function, the mechanisms by which it acts remain unclear. Here, we present
      evidence indicating that Fgf8 is not instructive in establishing zebrafish
      cerebellar cell identities, although it is required for proliferation and
      morphogenesis of this territory. We first show that, as in mouse, lack of Otx
      function in zebrafish leads to transformation of the presumptive mesencephalon
      into an extended rhombomere 1 (r1). Expanded Fgf8 expression was proposed to be
      the cause of this fate transformation. However, this report demonstrates that
      zebrafish embryos lacking both Otx and fgf8 functions retain an extended r1 and
      display differentiation of at least two cerebellar cell fates. We show that this
      is not caused by presence of other Fgfs, which implies that in absence of Otx,
      Fgf function is not necessary for the differentiation of cerebellar cell types.
      Otx proteins are therefore potent repressors of cerebellar fates, kept out of r1
      progeny by Fgf8. Because Otx transcripts are not present in presumptive r1
      territory prior to fgf8 expression, Fgf8 is required to maintain, rather than
      induce, the posterior boundary of Otx expression. This maintenance is enough to
      allow cerebellar differentiation.

PMID- 16611694
TI  - Medaka simplet (FAM53B) belongs to a family of novel vertebrate genes controlling
      cell proliferation.
AB  - The identification of genes that regulate proliferation is of great importance to
      developmental biology, regenerative medicine and cancer research. Using an in
      situ screen on a cortical structure of the medaka fish brain, we identified the
      simplet gene (smp), which is homologous to the human FAM53B gene. smp was
      expressed in actively proliferating cells of the CNS throughout embryogenesis. It
      belongs to a family of vertebrate-specific genes with no characterized
      biochemical domains. We showed that FAM53B bound 14-3-3 chaperones, as well as
      SKIIP proteins, adaptor proteins connecting DNA-binding proteins to modulators of
      transcription. smp inactivation with morpholinos led to delayed epiboly and
      reduced embryonic size. Absence of Smp activity did not induce apoptosis, but
      resulted in a reduced cell proliferation rate and enlarged blastomeres. Moreover,
      smp was shown to control the expression of the pluripotency-associated
      oct4/pou5f1 gene. We propose that smp is a novel vertebrate-specific gene needed
      for cell proliferation and that it is probably associated with the maintenance of
      a pluripotent state.

PMID- 16611695
TI  - Retinoic acid guides eye morphogenetic movements via paracrine signaling but is
      unnecessary for retinal dorsoventral patterning.
AB  - Retinoic acid (RA) is required for patterning of the posterior nervous system,
      but its role in the retina remains unclear. RA is synthesized in discrete regions
      of the embryonic eye by three retinaldehyde dehydrogenases (RALDHs) displaying
      distinct expression patterns. Overlapping functions of these enzymes have
      hampered genetic efforts to elucidate RA function in the eye. Here, we report
      Raldh1, Raldh2 and Raldh3 single, double and triple null mice exhibiting
      progressively less or no RA synthesis in the eye. Our genetic studies indicate
      that RA signaling is not required for the establishment or maintenance of
      dorsoventral patterning in the retina, as we observe normal expression of Tbx5
      and ephrin B2 (Efnb2) dorsally, plus Vax2 and Ephb2 ventrally. Instead, RA is
      required for the morphogenetic movements needed to shape the developing retina
      and surrounding mesenchyme. At early stages, Raldh2 expressed in mesenchyme and
      Raldh3 expressed in the retinal pigmented epithelium generate RA that delivers an
      essential signal to the neural retina required for morphogenetic movements that
      lead to ventral invagination of the optic cup. At later stages, Raldh1 expressed
      in dorsal neural retina and Raldh3 expressed in ventral neural retina (plus
      weaker expression of each in lens/corneal ectoderm) generates RA that travels to
      surrounding mesenchyme, where it is needed to limit the anterior invasion of
      perioptic mesenchyme during the formation of corneal mesenchyme and eyelids. At
      all stages, RA target tissues are distinct from locations of RA synthesis,
      indicating that RALDHs function cell-nonautonomously to generate paracrine RA
      signals that guide morphogenetic movements in neighboring cells.

PMID- 16611696
TI  - Orexigenic effects of a growth hormone secretagogue and nitric oxide in aged rats
      and dogs: correlation with the hypothalamic expression of some
      neuropeptidergic/receptorial effectors mediating food intake.
AB  - Hypothalamic neurochemical alterations in mammals underlie disturbances of food
      intake. There is scarce information on these topics in elderly persons;
      therefore, the aims of the present study were: (i) to evaluate the orexigenic
      effects of a growth hormone secretagogue, administered to young and old rats and
      dogs, alone or in combination with molsidomine, a donor of nitric oxide and (ii)
      to evaluate by reverse transcription-polymerase chain reaction in the whole
      hypothalamus of young and old rats messenger RNA levels of a wide number of
      anabolic and catabolic peptides, receptors, and enzymes involved in the control
      of feeding behavior, relating the detected titers, whenever possible, to the
      feeding responses to growth hormone secretagogue. In all, the results obtained
      strengthen the proposition that, in the hypothalamus of old rats, anti
      anorexigenic compensatory mechanisms are operative, aimed at maintaining a
      "normal" feeding pattern. Thus, the occurrence of a primary, age-related
      alteration in the feeding mechanisms is unlikely.

PMID- 16611697
TI  - Adipocytokines and lipid levels in Ames dwarf and calorie-restricted mice.
AB  - Ames dwarf mice are long-lived and insulin sensitive, and have a normal or
      reduced percentage of body fat. Calorie restriction (CR) is known to improve
      insulin sensitivity and reduce body fat. The purpose of this study was to
      evaluate the mechanism of improved insulin sensitivity in the Ames dwarfs and the
      effects of CR on adipose signaling and metabolism in normal and dwarf mice.
      Enhanced insulin sensitivity in dwarf mice may be partly due to increased release
      of adiponectin and the reduced release of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-6 (IL-6). Altered levels of adipocytokines might be consequent to
      the decreased lipid synthesis, plasma triglycerides, and free fatty acid levels.
      In normal mice, CR improves insulin sensitivity by affecting the release of
      adipocytokines, and decreasing circulating fatty acid and triglycerides
      concentrations as well as liver triglyceride accumulation. However, CR may reduce
      rather than enhance some of the insulin effects in the highly insulin-sensitive
      dwarf mice.

PMID- 16611698
TI  - Proteomic analysis of nitrated and 4-hydroxy-2-nonenal-modified serum proteins
      during aging.
AB  - Using proteomic techniques, we investigated peroxynitrite (ONOO-) and 4-hydroxy-2
      nonenal (HNE) modified serum proteins from young and old Fischer 344 rats. Two
      dimensional gel electrophoresis/western blot analysis of nitrotyrosine and HNE
      histidine revealed that serum proteins were differentially modified by ONOO- and
      HNE. Among them, 16 of the modified proteins, identified by matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), are
      involved in blood coagulation, lipid transport, blood pressure regulation, and
      protease inhibition. Furthermore, nitration and HNE adduction were found to
      increase with age, lending support to the oxidative stress hypothesis of aging.
      Our data showed that proteomic techniques can be valuable tools in the study of
      protein profiling modifications during aging.

PMID- 16611699
TI  - The effect of aging on anaerobic and aerobic enzyme activities in human skeletal
      muscle.
AB  - The effect of aging on metabolic enzyme activity remains controversial, possibly
      due to physical activity differences. We examined the effect of aging on the
      enzyme activity for anaerobic and aerobic pathways in nonweight-bearing human
      skeletal muscle from relatively sedentary males. The muscle obliquus internus
      abdominis was analyzed for anaerobic (creatine kinase, adenylate kinase, and
      lactate dehydrogenase) and aerobic (2-oxoglutarate dehydrogenase and carnitine
      palmitoyltransferase) enzyme activities in two groups: middle-aged (29-54 years)
      and older (61-74 years) adults. All enzyme activities were lower in older versus
      middle-aged adults when results were expressed as muscle wet weight (p <.05).
      When activity was expressed relative to the protein content, only lactate
      dehydrogenase remained significantly lower in older versus middle-aged adults (p
      <.001). In conclusion, some of the reduction in muscle performance in older
      adults may be due to lower activity of the anaerobic and aerobic enzymes as well
      as protein content, not solely due to a decrease in physical activity.

PMID- 16611700
TI  - Siblings of Okinawan centenarians share lifelong mortality advantages.
AB  - Okinawa, an isolated island prefecture of Japan, has among the highest prevalence
      of exceptionally long-lived individuals in the world; therefore, we hypothesized
      that, within this population, genes that confer a familial survival advantage
      might have clustered. We analyzed the pedigrees of 348 centenarian families with
      1142 siblings and compared sibling survival with that of the 1890 Okinawan
      general population cohort. Both male and female centenarian siblings experienced
      approximately half the mortality of their birth cohort-matched counterparts. This
      mortality advantage was sustained and did not diminish with age in contrast to
      many environmentally based mortality gradients, such as education and income.
      Cumulative survival advantages for this centenarian sibling cohort increased over
      the life span such that female centenarian siblings had a 2.58-fold likelihood,
      and male siblings a 5.43-fold likelihood, versus their birth cohorts, of reaching
      the age of 90 years. These data support a significant familial component to
      exceptional human longevity.

PMID- 16611701
TI  - Chromosome 4q25, microsomal transfer protein gene, and human longevity: novel
      data and a meta-analysis of association studies.
AB  - Recently, chromosome 4q25 was linked to exceptional human longevity, and a
      haplotype of the positional candidate microsomal transfer protein (MTP) gene was
      associated to the phenotype in U.S. Caucasians. We investigated whether linkage
      to 4q25 could be detected in 164 nonagenarian sibships of the Leiden Longevity
      Study. Additionally, we compared the MTP -493G/T and Q95H allele and haplotype
      frequencies in the Leiden Longevity Study (379 nonagenarians, 525 of their
      offspring, and 251 partners of their offspring) and in the Leiden 85-Plus Study
      (655 octogenarians and 244 young controls). The latter study population was
      followed for at least 7 years, providing the opportunity to perform also
      prospective analyses using the longitudinal data. We found neither evidence for
      linkage at 4q25 nor association of the MTP locus with longevity in nonagenarian
      individuals. Meta-analyses of all previous studies implied that the association
      in U.S. Caucasians may have its source in admixture of the U.S. control
      population rather than in the genetic effect of the locus on exceptional
      longevity.

PMID- 16611702
TI  - Meeting the needs of disabled older persons: can the fragments be pieced
      together?

PMID- 16611703
TI  - A system of integrated care for older persons with disabilities in Canada:
      results from a randomized controlled trial.
AB  - BACKGROUND: Care for elderly persons with disabilities is usually characterized
      by fragmentation, often leading to more intrusive and expensive forms of care
      such as hospitalization and institutionalization. There has been increasing
      interest in the ability of integrated models to improve health, satisfaction, and
      service utilization outcomes. METHODS: A program of integrated care for
      vulnerable community-dwelling elderly persons (SIPA [French acronym for System of
      Integrated Care for Older Persons]) was compared to usual care with a randomized
      control trial. SIPA offered community-based care with local agencies responsible
      for the full range and coordination of community and institutional (acute and
      long-term) health and social services. Primary outcomes were utilization and
      public costs of institutional and community care. Secondary outcomes included
      health status, satisfaction with care, caregiver burden, and out-of-pocket
      expenses. RESULTS: Accessibility was increased for health and social home care
      with increased intensification of home health care. There was a 50% reduction in
      hospital alternate level inpatient stays ("bed blockers") but no significant
      differences in utilization and costs of emergency department, hospital acute
      inpatient, and nursing home stays. For all study participants, average community
      costs per person were C dollar 3390 higher in the SIPA group but institutional
      costs were C dollar 3770 lower with, as hypothesized, no difference in total
      overall costs per person in the two groups. Satisfaction was increased for SIPA
      caregivers with no increase in caregiver burden or out-of-pocket costs. As
      expected, there was no difference in health outcomes. CONCLUSIONS: Integrated
      systems appear to be feasible and have the potential to reduce hospital and
      nursing home utilization without increasing costs.

PMID- 16611704
TI  - Functional decline in patients with and without peripheral arterial disease:
      predictive value of annual changes in levels of C-reactive protein and D-dimer.
AB  - BACKGROUND: Inflammation may be a potential mechanism of aging-related functional
      decline. We determined whether greater annual increases in levels of high
      sensitivity C-reactive protein (hsCRP) and D-dimer predicted greater decline in
      functioning among persons with and without lower extremity peripheral arterial
      disease (PAD). METHODS: We prospectively studied 296 men and women with PAD and
      191 without PAD. Objective measures of functioning, hsCRP, and D-dimer were
      obtained at baseline and annually for 3 years (mean follow-up = 36.3 +/- 6.4
      months). RESULTS: Among PAD participants, greater annual increases in hsCRP were
      associated with greater annual declines in 6-minute walk performance (-2.63
      ft/mg/L, p =.039) but not in other functional outcomes. Higher prior year
      absolute hsCRP levels were associated with greater declines in 6-minute walk (
      2.93 ft/mg/L, p =.022), summary performance score (-0.038/mg/L, p =.017), and
      rapid paced 4-meter walk (-0.29 cm/s/mg/L, p =.026) during the subsequent year.
      Among participants without PAD, greater annual increases in hsCRP were associated
      with greater annual declines in 6-minute walk (-7.47 ft/mg/L, p =.002), usual
      pace 4-meter walk (-0.33 cm/s/mg/L, p <.001), fast paced 4-meter walk (-0.56
      cm/s/mg/L, p =.003), and the summary performance score (-0.029 mg/L, p <.001).
      There were no consistent associations between D-dimer levels and functional
      decline. CONCLUSION: These findings suggest that inflammation may play a role in
      functional decline in persons with and without PAD.

PMID- 16611705
TI  - Linking C-reactive protein to late-life disability in the National Health and
      Nutrition Examination Survey (NHANES) 1999-2002.
AB  - BACKGROUND: Chronic inflammation, measured by interleukin-6, predicts incident
      disability among elderly people. However, little is known about the relation of C
      reactive protein (CRP) to disability. METHOD: Participants (>60 years old, N =
      1680) were from the National Health and Nutrition Examination Survey 1999-2002.
      Disability in activities of daily living (ADL), instrumental activities of daily
      living (IADL), leisure and social activities (LSA), lower extremity mobility
      (LEM), and general physical activities (GPA) was obtained by self-report. Peak
      muscle power was the product of isokinetic peak leg torque and peak force
      velocity. Functional limitations were evaluated via habitual walking speed, which
      was obtained from a 20-foot timed walk. CRP levels were quantified by using latex
      enhanced nephelometry. RESULTS: Elevated CRP levels were associated with
      disability in IADL, LSA, LEM, and GPA, independent of basic demographics, chronic
      medical diseases, health behaviors, as well as nutritional markers. The
      corresponding odds ratios of disability for each standard-deviation increase in
      natural-log-transformed CRP were 1.18 (95% confidence interval [CI], 1.02-1.35),
      1.18 (95% CI, 1.00-1.39), 1.17 (95% CI, 1.03-1.33), and 1.17 (95% CI, 1.05-1.31),
      respectively. The relationship diminished after additional adjustment of leg
      power and/or walking speed, meaning that impairment in leg power and limitations
      in gait speed likely mediate the association between CRP and disability. CRP had
      an inverse relationship to leg power and walking speed. Likewise, additional
      adjustment for leg power substantially diminished the association between CRP and
      walking speed, suggesting a mediating effect of power between CRP and gait speed.
      CONCLUSIONS: Independent of chronic diseases, elevated CRP is associated with
      multiple domains of disability through mediation of muscle power, habitual gait
      speed, or both. Future research is needed to understand CRP as a risk factor for
      disability in older populations.

PMID- 16611706
TI  - Physical activity status, but not age, influences inflammatory biomarkers and
      toll-like receptor 4.
AB  - BACKGROUND: Chronic inflammation has been implicated in the development of
      cardiovascular disease, diabetes mellitus, cachexia, and osteoporosis. Regular
      physical activity has been purported to possess "anti-inflammatory" properties
      which may limit chronic inflammation. Recently, we hypothesized that toll-like
      receptor 4 (TLR4) may play a role in activity-induced modulation of inflammation.
      Therefore, the purpose of this study was to determine the association between
      age, physical activity status, biomarkers of inflammation, and TLR4. METHODS:
      Male and female participants (n = 84) were recruited to fill one of the following
      groups: young (18-30 years), active; young, inactive; old (60-80 years), active;
      or old, inactive. To assess physical activity status, participants completed a
      Paffenbarger Physical Activity Questionnaire and a modified Balke submaximal
      treadmill test. After grouping and screening, participants were given a standard
      mixed diet to consume 24 hours prior to arriving at the laboratory. Participants
      were instructed to consume all food by 10 pm the night prior to blood sampling (8
      hour fast). Following 30 minutes of seated rest in a quiet room, venous blood
      samples were collected. Lipopolysaccharide-stimulated inflammatory cytokine
      production and plasma high-sensitivity C-reactive protein (hsCRP) were determined
      by enzyme-linked immunosorbent assay, and TLR4 expression was determined by flow
      cytometry. RESULTS: Lipopolysaccharide-stimulated interleukin-6, interleukin
      1beta, and tumor necrosis factor-alpha production, TLR4 expression, and hsCRP
      were significantly lower in active compared to inactive participants (p <.05).
      Also, older participants had significantly higher hsCRP than young participants
      had (p <.05). CONCLUSIONS: The findings of the present study support previous
      reports which infer that acute exercise or a physically active lifestyle may
      possess anti-inflammatory properties. Also this study, along with previous work
      from our laboratory, suggests that TLR4 may play a role in regulating the link
      between inflammatory cytokine production and a physically active lifestyle.

PMID- 16611707
TI  - Predictors of falls in a multiethnic population of older rural adults with
      diabetes.
AB  - BACKGROUND: Falls are a recognized danger for older adults with diabetes. Persons
      in rural communities with diabetes may face additional risks from falling due to
      environmental and activity differences. METHODS: Data were obtained in a cross
      sectional survey of a stratified random sample of 691 community-dwelling adults
      (42.7% white, 31.4% African American, and 25.9% Native American) at least 65
      years old with two or more Medicare claims for diabetes in 1998-2000, living in
      two rural counties in North Carolina. Falls data were self-reported for the
      previous year. Demographic data, foot-related symptoms, diabetes medications, and
      other health characteristics were reported. RESULTS: Three hundred two persons
      (43.7%) reported falling at least once, including 171 (26.2%) who experienced two
      or more (frequent) falls. Frequent fallers were more likely to be male (odds
      ratio [OR] = 1.76; 95% confidence interval [CI] = 1.17, 2.66), report tingling or
      numbness in feet (OR = 1.75; 95% CI = 1.13, 2.70), have had a stroke (OR = 1.81;
      95% CI = 1.19, 2.76), have longer duration of diabetes (OR = 1.21; 95% CI = 1.00,
      1.47), have lower physical functioning (OR = 0.97; 95% CI = 0.96, 0.99) and
      mobility (OR = 0.89; 95% CI = 0.82, 0.96), and take a greater number of
      prescription medications (OR = 1.07; 95% CI = 1.01, 1.13). CONCLUSIONS: For rural
      older adults with diabetes, falls history should be screened to identify those at
      risk. Further research should investigate unique environmental factors
      contributing to falls for rural elderly persons.

PMID- 16611708
TI  - Impact of falls on the balance, gait, and activities of daily living functioning
      in community-dwelling Chinese older adults.
AB  - OBJECTIVE: The objective of the present study was to investigate the impact of
      incident falls on the balance, gait, and Activities of Daily Living functioning
      in community-dwelling older adults. METHODS: This was a population-based, 1-year
      prospective cohort study in older adults. We performed baseline assessment of
      potential predictors, the 1-year occurrence of falls, and then 1-year
      reassessment of the following outcome measures: the Barthel Index (BI), Lawton's
      Instrumental Activities of Daily Living (IADL) scale, gait speed, and Tinetti
      Balance and Gait Evaluation's total mobility score (TMS). At 1 year of follow-up,
      participants who had declined by > or = 1 standard deviation (SD) below the
      baseline mean value of each outcome measure were classified as "decliners."
      RESULTS: Of the 1517 participants, 93.5% (n = 1419) completed the 1-year follow
      up reassessment of BI and IADL. For gait speed and TMS, respectively, 88.2% (n =
      1338) and 88.3% (n = 1339) completed the 1-year outcome assessment. Fallers,
      particularly recurrent fallers, experienced significantly greater 1-year declines
      in the four functional measures. Multivariate logistic regression analyses showed
      that an incident fall was a significant independent predictor for decliners in
      the BI, Lawton's IADL score, gait speed, and TMS after adjustment of all
      significant confounding factors. The relative risks of an incident fall as an
      independent predictor for decliners in the BI, IADL score, gait speed, and TMS
      were 2.4 (95% confidence interval [CI], 1.4-4.0; p =.01), 2.9 (95% CI, 1.7-5.2; p
      <.001), 2.4 (95% CI, 1.5-3.8; p <.001), and 4.6 (95% CI, 2.7-7.8; p <.001),
      respectively. CONCLUSIONS: Incident falls have a significant negative impact on
      the balance, gait, and Activities of Daily Living functioning in community
      dwelling older adults.

PMID- 16611709
TI  - Poor sleep is associated with impaired cognitive function in older women: the
      study of osteoporotic fractures.
AB  - BACKGROUND: The association between objectively measured sleep and cognition
      among community-dwelling elderly persons remains understudied. This
      observational, cross-sectional analysis examined this association. METHODS:
      Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic
      Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental
      State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment
      was defined as MMSE < 26 or Trails B > 278 seconds. Sleep parameters measured
      objectively using actigraphy included total sleep time, sleep efficiency, sleep
      latency, wake after sleep onset (WASO), and total nap time. RESULTS: There were
      305 women (10.6%) with MMSE < 26 and 257 women (9.3%) with Trails B > 278
      seconds. Compared with women with sleep efficiency > or = 70%, those with <70%
      had a higher risk of cognitive impairment (MMSE < 26 multivariate odds ratio
      [MOR] = 1.61; 95% confidence interval [CI], 1.20-2.16; Trails B > 278 MOR = 1.96;
      95% CI, 1.43-2.67). Higher sleep latency was associated with higher risk of
      cognitive impairment (per half hour: MMSE < 26 MOR = 1.23; 95% CI, 1.13-1.33;
      Trails B > 278 MOR = 1.13; 95% CI, 1.04-1.24), as was higher WASO (per half hour:
      MMSE < 26 MOR = 1.15; 95% CI, 1.06-1.23; Trails B > 278 MOR = 1.24; 95% CI, 1.15
      1.34). Women who napped > or = 2 hours per day had a higher risk (MMSE < 26 MOR =
      1.42; 95% CI, 1.05-1.93; Trails B > 278 MOR = 1.74; 95% CI, 1.26-2.40). There was
      no significant relationship for total sleep time. CONCLUSION: Objectively
      measured disturbed sleep was consistently related to poorer cognition, whereas
      total sleep time was not. This finding may suggest that it is disturbance of
      sleep rather than quantity that affects cognition.

PMID- 16611710
TI  - Medication utilization in an urban homebound population.
AB  - BACKGROUND: The number of medically homebound adults has grown with the aging of
      the U.S. population, yet little is known about their health care utilization. We
      sought to characterize the health status and medication utilization of an urban
      cohort of homebound adults and to identify factors associated with medication use
      in this population. METHODS: We performed a retrospective cross-sectional
      analysis of 415 patients enrolled in a primary care program for homebound adults
      in New York City during October 2002. Numbers of medications were obtained from
      formularies corroborated by home visits. For patients without prescription
      insurance, medication out-of-pocket costs were estimated according to average
      wholesale pricing. Sociodemographic and disease characteristics were obtained by
      chart abstraction. RESULTS: The median age was 83 years (range 25-106 years).
      Seventy-seven percent of patients were female, 63% were non-white, and 28% spoke
      Spanish. Sixty-four percent of patients had Medicaid. The cohort had a mean of
      8.2 (range 1-27, standard deviation 4.5) medications prescribed per month.
      Multivariate analysis showed that increasing age was associated with fewer
      medications (p <.001). Charlson comorbidity score was positively associated with
      number of medications (p <.001), whereas Activities of Daily Living score, a
      measure of functional dependence, was not. Twenty-seven percent of the cohort
      lacked prescription drug coverage. The total number of medications per month
      among the uninsured patients was 7.4 (standard deviation 4.4). Estimated median
      monthly out-of-pocket cost for the uninsured patients was dollar 223 (range
      dollar 1-dollar 1512). CONCLUSIONS: For homebound patients without prescription
      drug coverage, medication use may represent substantial financial burden.
      Additional research is needed to determine whether out-of-pocket medication costs
      represent a barrier to care in this population.

PMID- 16611711
TI  - Early detection of progressive chronic kidney disease: is it feasible?

PMID- 16611712
TI  - Genetic investigation of autosomal recessive distal renal tubular acidosis:
      evidence for early sensorineural hearing loss associated with mutations in the
      ATP6V0A4 gene.
AB  - Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of
      apical H(+) ATPase, cause recessive forms of distal renal tubular acidosis
      (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing
      loss (SNHL), whereas ATP6V0A4 mutations are classically associated with either
      late-onset SNHL or normal hearing. The phenotype and genotype of 39 new kindreds
      with recessive dRTA, 18 of whom were consanguineous, were assessed. Novel and
      known loss-of-function mutations were identified in 31 kindreds. Fourteen new and
      five recurrent mutations of the ATP6V0A4 gene were identified in 21 families. For
      the ATP6V1B1 gene, two new and two previously described mutations were identified
      in 10 families. Surprisingly, seven probands with ATP6V0A4 gene mutations
      developed severe early SNHL between the ages of 2 mo and 10 yr. No mutation was
      detected in eight families. These data extend the spectrum of disease-causing
      mutations and provide evidence for genetic heterogeneity in SNHL. The data also
      demonstrate that mutations in either of these genes may cause early deafness, and
      they highlight the importance of genetic screening for recessive forms of dRTA
      independent of hearing status.

PMID- 16611713
TI  - Autosomal dominant pseudohypoaldosteronism type 1: mechanisms, evidence for
      neonatal lethality, and phenotypic expression in adults.
AB  - Autosomal dominant pseudohypoaldosteronism type 1 (adPHA1) is a rare condition
      that is characterized by renal resistance to aldosterone, with salt wasting,
      hyperkalemia, and metabolic acidosis. It is thought of as a mild disorder;
      affected children's symptoms respond promptly to salt therapy, and treatment is
      not required after childhood. Mutations in the mineralocorticoid receptor gene
      (MR) cause adPHA1, but the long-term consequences of MR deficiency in humans are
      not known. Herein are described six novel adPHA1-causing MR mutations (four de
      novo) and evidence that haploinsufficiency of MR is sufficient to cause adPHA1.
      Furthermore, genotype-phenotype correlation is reported in a large adPHA1
      kindred. A number of cases of neonatal mortality in infants who were at risk for
      adPHA1 were identified; coupled with the frequent identification of de novo
      mutations in affected individuals, this suggests that the seemingly benign adPHA1
      may have been a fatal neonatal disorder in previous eras, preventing propagation
      of disease alleles. In contrast, it is shown that adult patients with adPHA1 are
      clinically indistinguishable from their wild-type relatives except for presumably
      lifelong elevation of renin, angiotensin II, and aldosterone levels. These data
      highlight the critical role of MR in the maintenance of salt homeostasis early in
      life and illuminate the sodium dependence of pathologic effects of renin and
      angiotensin II. They furthermore argue that nongenomic effects of aldosterone
      play no significant role in the long-term development of cardiovascular disease.

PMID- 16611714
TI  - Non-contrast-enhanced computerized tomography and analgesic-related kidney
      disease: report of the national analgesic nephropathy study.
AB  - Previous studies suggested that the non-contrast-enhanced computerized tomography
      (CT) scan is a highly reliable tool for the diagnosis of analgesic-associated
      renal disease. However, this issue has not been addressed in the US population. A
      total of 221 incident patients with ESRD from different regions of the United
      States underwent a helical CT scan and detailed questioning about drug history.
      Specific renal anatomic criteria were developed to determine whether a
      constellation of CT findings (small indented calcified kidneys [SICK]) is linked
      to analgesic ingestion. For approximating use before the onset of renal disease,
      only analgesic ingestion at least 9 yr before starting dialysis was considered
      relevant. Fifteen patients met the criteria for SICK. This represented 7% of the
      enrolled patients and approximately 1% of the total ESRD population. There was a
      significant increase in the estimated risk among patients with a history of heavy
      aspirin ingestion (odds ratio [OR] 7.4 [95% confidence interval (CI) 1.2 to 43]
      for > or =1 kg lifetime; OR 8.8 [95% CI 1.2 to 66] for > or =0.3 kg/yr). Total
      analgesic ingestion of > or =0.3 kg/yr also was significantly associated with
      SICK (OR 8.2; 95% CI 1.5 to 45). These findings were accounted for largely by
      combination products that contained aspirin and phenacetin (used by three
      patients with SICK), which are no longer available. In addition, the CT finding
      of SICK was present only in a minority of heavy analgesic users, yielding a
      sensitivity of 5 to 26%. Findings of SICK are infrequent in the US ESRD
      population and do not occur among a sufficient proportion of heavy analgesic
      users to render the non-contrast-enhanced CT scan a sensitive tool to detect
      analgesic-associated kidney injury.

PMID- 16611715
TI  - Association of single measurements of dipstick proteinuria, estimated glomerular
      filtration rate, and hematocrit with 25-year incidence of end-stage renal disease
      in the multiple risk factor intervention trial.
AB  - The incidence of ESRD is increasing rapidly. Limited information exists regarding
      early markers for the development of ESRD. This study aimed to determine over 25
      yr the risk for ESRD associated with proteinuria, estimated GFR (eGFR), and
      hematocrit in men who did not have identified kidney disease and were randomly
      assigned into the Multiple Risk Factor Intervention Study (MRFIT). A total of
      12,866 men who were at high risk for heart disease were enrolled (1973 to 1975)
      and followed through 1999. Renal replacement therapy was ascertained by matching
      identifiers with the United States Renal Data System's data; vital status was
      from the National Death Index. Men who initiated renal replacement therapy or
      died as a result of kidney disease were deemed to have developed ESRD. Dipstick
      urine for proteinuria, eGFR, and hematocrit were related to development of ESRD.
      During 25 yr, 213 (1.7%) men developed ESRD. Predictors of ESRD were dipstick
      proteinuria of 1+ or > or =2+ (hazard ratio [HR] 3.1 [95% confidence interval
      (CI) 1.8 to 5.4] and 15.7 [95% CI 10.3 to 23.9] respectively) and an eGFR of <60
      ml/min per 1.73 m(2) (HR 2.4; 95% CI 1.5 to 3.8). Correlation between eGFR and
      serum creatinine was 0.9; the risk for ESRD with a 1-SD difference of each was
      identical (HR 1.21). Bivariate analysis demonstrated a 41-fold increase in ESRD
      risk in those with an eGFR <60 ml/min per 1.73 m(2) and > or =2+ proteinuria (95%
      CI 15.2 to 71.1). There was no association between hematocrit and ESRD. Other
      baseline measures that independently predicted ESRD included age, cigarette
      smoking, BP, low HDL cholesterol, and fasting glucose. Among middle-aged men who
      were at high risk for cardiovascular disease but had no clinical evidence of
      cardiovascular disease or significant kidney disease, dipstick proteinuria and an
      eGFR value <60 ml/min per 1.73 m(2) were strong predictors of long-term
      development of ESRD. It remains unknown whether intervention for proteinuria or
      early identification of those with chronic kidney disease reduces the risk for
      ESRD.

PMID- 16611716
TI  - Uric acid and endothelial dysfunction in essential hypertension.
AB  - Recent epidemiologic and experimental evidence suggests that serum uric acid (UA)
      is an independent risk factor for cardiovascular and renal diseases. However,
      endothelial dysfunction is an early predictor of cardiovascular events,
      particularly in hypertensive patients. For assessment of the association between
      UA and endothelial function, 217 (108 men, 109 women; aged 48.0 +/- 10.6 yr)
      white never-treated hypertensive patients were studied. All patients underwent
      the following procedures: BP measurements, laboratory tests (C-reactive protein
      [CRP], insulin resistance by homeostasis model assessment, serum creatinine, and
      UA), and endothelial function evaluated by intra-arterial infusion of
      acetylcholine (ACh). Serum creatinine, CRP, and maximal vasodilatory response to
      ACh were related to the UA (all P < 0.0001). In the multiple regression analysis,
      serum UA ranked as the third correlate of peak of forearm blood flow predictor,
      after homeostasis model assessment and CRP. The data show an independent link
      between UA and endothelial function, also in a statistical model that included
      CRP. In conclusion, the data demonstrate an inverse and significant relationship
      between UA and ACh-stimulated vasodilation in patients with uncomplicated,
      untreated essential hypertension, independent of traditional cardiovascular risk
      factors. Probably, the chronic inflammation that was documented in these patients
      may be considered the mechanistic link between serum UA and vascular damage.

PMID- 16611717
TI  - Podocyte-specific deletion of integrin-linked kinase results in severe glomerular
      basement membrane alterations and progressive glomerulosclerosis.
AB  - Alterations in glomerular podocyte cell-cell and cell-matrix contacts are key
      events in progressive glomerular failure. Integrin-linked kinase (ILK) has been
      implicated in podocyte cell-matrix interaction and is induced in proteinuria. For
      evaluation of ILK function in vivo, mice with a Cre-mediated podocyte-specific
      ILK inactivation were generated. These mice seemed normal at birth but developed
      progressive focal segmental glomerulosclerosis and died in terminal renal
      failure. The first ultrastructural lesions that are seen at onset of albuminuria
      are glomerular basement membrane (GBM) alterations with a significant increase in
      true harmonic mean GBM thickness. Podocyte foot process effacement and loss of
      slit diaphragm followed with progression to unselective proteinuria. No
      significant reduction of slit membrane molecules (podocin and nephrin), key GBM
      components (fibronectin, laminins, and collagen IV isoforms), or podocyte
      integrins could be observed at onset of proteinuria. However, alpha3-integrins
      were relocalized into a granular pattern along the GBM, consistent with altered
      integrin-mediated matrix assembly in ILK-deficient podocytes. As the increased
      GBM thickness precedes structural podocyte lesions and key components of the GBM
      were expressed at comparable levels to controls, these data suggest an essential
      role of ILK for the close interconnection of GBM structure and podocyte function.

PMID- 16611718
TI  - Isolation and confirmation of a calcium excretion quantitative trait locus on
      chromosome 1 in genetic hypercalciuric stone-forming congenic rats.
AB  - Hypercalciuria is the most common risk factor for kidney stones and has a
      substantial genetic component. The genetic hypercalciuric stone-forming (GHS) rat
      model displays complex changes in physiology involving intestine, bone, and
      kidney and overexpression of the vitamin D receptor, thereby reproducing the
      human phenotype of idiopathic hypercalciuria. Through quantitative trait locus
      (QTL) mapping of rats that were bred from GHS female rats and normocalciuric
      Wistar Kyoto (WKY) male rats, loci that are linked to hypercalciuria and account
      for a 6 to eight-fold phenotypic difference between the GHS and WKY progenitors
      were mapped. GHS x WKY rats were backcrossed to breed for congenic rats with the
      chromosome 1 QTL HC1 on a normocalciuric WKY background. Ten generations of
      backcrosses produced N10F1 rats, which were intercrossed to produce rats that
      were homozygous for GHS loci in the HC1 region between markers D1Mit2 and
      D1Mit32. On a high-calcium diet (1.2% calcium), significantly different levels of
      calcium excretion were found between male congenic (1.67 +/- 0.71 mg/24 h) and
      male WKY control rats (0.78 +/- 0.19 mg/24 h) and between female congenic (3.11
      +/- 0.90 mg/24 h) and female WKY controls (2.11 +/- 0.50 mg/24 h); the congenics
      preserve the calcium excretion phenotype of the GHS parent strain. Microarray
      expression analyses of the congenic rats, compared with WKY rats, showed that of
      the top 100 most changed genes, twice as many as were statistically expected
      mapped to chromosome 1. Of these, there is a clear bias in gene expression change
      for genes in the region of the HC1. Of >1100 gene groups analyzed, one third of
      the 50 most differentially expressed gene groups have direct or secondary action
      on calcium metabolism or transport. This is the first QTL for hypercalciuria to
      be isolated in a congenic animal.

PMID- 16611719
TI  - Early changes in bioelectrical estimates of body composition in chronic kidney
      disease.
AB  - The aim of this study was to detect the potential occurrence of early
      abnormalities of body composition in patients with chronic kidney disease (CKD)
      at first referral to an outpatient nephrology clinic. Eighty-four patients with
      CKD (49 men and 35 women) were compared with 604 healthy control subjects (298
      men and 306 women). Anthropometry and bioelectrical impedance analysis (BIA) were
      performed in all participants, whereas renal function, laboratory tests for
      nutritional status, and nutrient intake were assessed in the CKD group only.
      Creatinine clearance was 27.8 +/- 13.8 and 27.4 +/- 13.0 ml/min per 1.73 m(2) in
      male and female patients with CKD, respectively. No patient showed peripheral
      edema; frank malnutrition, defined by presence of serum albumin <3.5 g/dl plus
      body mass index <20 kg/m(2); or protein intake <0.6 g/kg per d. At the BIA,
      patients with CKD showed lower resistance (R) and abnormal mean impedance vectors
      for the bivariate normal distribution of R/height and reactance/height. Phase
      angle also was reduced (-22%), especially in patients with diabetes. When BIA
      derived data were considered, total body water was slightly higher (+4.3% in men;
      +3.5% in women) and body cell mass was lower (-6.7% in men; -7.7% in women) in
      patients with CKD. No difference in either BIA parameters or nutritional indexes
      was observed among various CKD stages. Despite the absence of overt malnutrition,
      patients with CKD exhibit altered BIA variables from the early phases of renal
      disease. These alterations are related to the renal dysfunction, are more marked
      in the presence of diabetes, and mainly indicate the presence of overhydration in
      the absence of edema. Therefore, BIA represents an attractive clinical tool to
      detect impairment of body composition from the early stages of CKD.

PMID- 16611720
TI  - Chronic kidney disease causes defects in signaling through the insulin receptor
      substrate/phosphatidylinositol 3-kinase/Akt pathway: implications for muscle
      atrophy.
AB  - Complications of chronic kidney disease (CKD) include depressed responses to
      insulin/IGF-1 and accelerated muscle proteolysis as a result of activation of
      caspase-3 and the ubiquitin-proteasome system. Experimentally, proteolysis in
      muscle cells occurs when there is suppression of phosphatidylinositol 3-kinase
      (PI3-K) activity. Postreceptor signaling through the insulin receptor substrate
      (IRS)/PI3-K/Akt pathway was evaluated in muscles of acidotic, CKD and pair-fed
      control rats under physiologic conditions and in response to a dose of insulin
      that quickly stimulated the pathway. Basal IRS-1-associated PI3-K activity was
      suppressed by CKD; IRS-2-associated PI3-K activity was increased. The basal level
      of activated Akt in CKD muscles also was low, indicating that the higher IRS-2
      associated PI3-K activity did not compensate for the reduced IRS-1-associated PI3
      K activity. Insulin treatment overcame this abnormality. The low IRS-1-associated
      PI3-K activity in muscle was not due to a decrease in IRS-1 protein, but there
      was a higher amount of the PI3-K p85 subunit protein without a concomitant
      increase in the p110 catalytic subunit, offering a potential explanation for the
      lower IRS-1-associated PI3-K activity. Eliminating the acidosis of CKD partially
      corrected the decrease in basal IRS-1-associated PI3-K activity and protein
      degradation in muscle. It is concluded that in CKD, acidosis and an increase in
      the PI3-K p85 subunit are mechanisms that contribute to suppression of PI3-K
      activity in muscle, and this leads to accelerated muscle proteolysis.

PMID- 16611721
TI  - Aerobic capacity and peak power output of elite quadriplegic games players.
AB  - BACKGROUND: Participation in wheelchair sports such as tennis and rugby enables
      people with quadriplegia to compete both individually and as a team at the
      highest level. Both sports are dominated by frequent, intermittent, short term
      power demands superimposed on a background of aerobic activity. OBJECTIVE: To
      gain physiological profiles of highly trained British quadriplegic athletes, and
      to examine the relation between aerobic and sprint capacity. METHODS: Eight male
      quadriplegic athletes performed an arm crank exercise using an ergometer fitted
      with a Schoberer Rad Messtechnik (SRM) powermeter. The sprint test consisted of
      three maximum-effort sprints of five seconds duration against a resistance of 2%,
      3%, and 4% of body mass. The highest power output obtained was recorded (PPO).
      Peak oxygen consumption (V(O2peak)), peak heart rate (HR(peak)), and maximal
      power output (PO(aer)) were determined. RESULTS: Mean PO(aer) was 67.7 (16.2) W,
      mean V(O2peak) was 0.96 (0.17) litres/min, and HR(peak) was 134 (19) beats/min
      for the group. There was high variability among subjects. Peak power over the
      five second sprint for the group was 220 (62) W. There was a significant
      correlation between V(O2peak) (litres/min) and PO(aer) (W) (r = 0.74, p<0.05).
      CONCLUSIONS: These British quadriplegic athletes have relatively high aerobic
      fitness when compared with the available literature. Moreover, the anaerobic
      capacity of these athletes appeared to be relatively high compared with
      paraplegic participants.

PMID- 16611722
TI  - Cryotherapy for acute ankle sprains: a randomised controlled study of two
      different icing protocols.
AB  - BACKGROUND: The use of cryotherapy in the management of acute soft tissue injury
      is largely based on anecdotal evidence. Preliminary evidence suggests that
      intermittent cryotherapy applications are most effective at reducing tissue
      temperature to optimal therapeutic levels. However, its efficacy in treating
      injured human subjects is not yet known. OBJECTIVE: To compare the efficacy of an
      intermittent cryotherapy treatment protocol with a standard cryotherapy treatment
      protocol in the management of acute ankle sprains. SUBJECTS: Sportsmen (n = 44)
      and members of the general public (n = 45) with mild/moderate acute ankle
      sprains. METHODS: Subjects were randomly allocated, under strictly controlled
      double blind conditions, to one of two treatment groups: standard ice application
      (n = 46) or intermittent ice application (n = 43). The mode of cryotherapy was
      standardised across groups and consisted of melting iced water (0 degrees C) in a
      standardised pack. Function, pain, and swelling were recorded at baseline and
      one, two, three, four, and six weeks after injury. RESULTS: Subjects treated with
      the intermittent protocol had significantly (p<0.05) less ankle pain on activity
      than those using a standard 20 minute protocol; however, one week after ankle
      injury, there were no significant differences between groups in terms of
      function, swelling, or pain at rest. CONCLUSION: Intermittent applications may
      enhance the therapeutic effect of ice in pain relief after acute soft tissue
      injury.

PMID- 16611723
TI  - Non-fatal horse related injuries treated in emergency departments in the United
      States, 2001-2003.
AB  - OBJECTIVE: To characterise and provide nationally representative estimates of
      persons with non-fatal horse related injuries treated in American emergency
      departments. METHODS: The National Electronic Injury Surveillance System All
      Injury Program (NEISS-AIP) is a stratified probability sample comprising 66
      hospitals. Data on injuries treated in these emergency departments are collected
      and reported. NEISS-AIP data on all types (horseback riding and otherwise) of non
      fatal horse related injuries from 2001 to 2003 were analysed. RESULTS: An
      estimated 102,904 persons with non-fatal horse related injuries (35.7 per 100,000
      population) were treated in American emergency departments each year from 2001 to
      2003 inclusive. Non-fatal injury rates were higher for females (41.5 per 100,000)
      than for males (29.8 per 100,000). Most patients were injured while mounted on a
      horse (66.1%), commonly from falling or being thrown by the horse; while not
      mounted, injuries most often resulted from being kicked by the horse. The body
      parts most often injured were the head/neck region (23.2%), lower extremity
      (22.2%), and upper extremity (21.5%). The most common principal diagnoses were
      contusions/abrasions (31.4%) and fractures (25.2%). For each year that was
      studied, an estimated 11 502 people sustained traumatic brain injuries from horse
      related incidents. Overall, more than 11% of those injured were admitted to
      hospital. CONCLUSIONS: Horse related injuries are a public health concern not
      just for riders but for anyone in close contact with horses. Prevention
      programmes should target horseback riders and horse caregivers to promote helmet
      use and educate participants about horse behaviour, proper handling of horses,
      and safe riding practices.

PMID- 16611724
TI  - Raised troponin T and echocardiographic abnormalities after prolonged strenuous
      exercise--the Australian Ironman Triathlon.
AB  - BACKGROUND: There is concern about whether cardiac damage occurs as a result of
      prolonged strenuous exercise. OBJECTIVE: To investigate whether competing in a
      triathlon is associated with cardiac damage based on a sustained increase in
      cardiac troponin T (cTnT), and whether such an increase correlates with
      echocardiographic changes METHODS: cTnT and echocardiographic measurements were
      made in 38 participants in the 2001 Australian ironman triathlon. cTnT was
      measured the day before, immediately after, and the day following the race.
      Echocardiography was done the day before, immediately after, and two to six weeks
      later for measurement of ejection fraction, stroke volume, cardiac output, wall
      motion analysis, and global left ventricular function (LVF). RESULTS: No subject
      had detectable cTnT in the pre-race sample. Following the race, 32 subjects
      (86.5%) had detectable levels of cTnT (>0.01 ng/ml), with six (16.2%) having
      >0.10 ng/ml. The day after the race, nine subjects (23.7%) still had detectable
      cTnT, with two recording a level >0.10 ng/ml. Previously described
      echocardiographic changes of "cardiac fatigue" were observed in the whole cohort.
      There was a modest but significant correlation between change in ejection
      fraction and peak cTnT level (p = 0.02, r = 0.39). Athletes with a post-race cTnT
      >0.10 ng/ml had a greater decrease in global LVF (p = 0.02) and a trend toward a
      greater fall in ejection fraction and stroke volume than athletes with cTnT
      levels <0.10 ng/ml. Cardiac output fell in the group with cTnT >0.10 ng/ml
      (p>0.05). CONCLUSIONS: Participation in ironman triathlon often resulted in
      persistently raised cTnT levels, and the troponin rise was associated with
      echocardiographic evidence of abnormal left ventricular function. The clinical
      significance and long term sequelae of such damage remains to be determined.

PMID- 16611725
TI  - Navicular stress fractures: outcomes of surgical and conservative management.
AB  - OBJECTIVE: To compare the long term outcomes of the two treatment options for
      navicular stress fractures: non-weightbearing cast immobilisation and surgical
      fixation. DESIGN: Retrospective case study. PARTICIPANTS: Subjects aged 18 years
      and older who had been treated for a navicular stress fracture more than two
      years previously. MAIN OUTCOME MEASURES: Questionnaire based analogue pain score
      and function score; tenderness on palpation; abnormality detected on computed
      tomography (CT). RESULTS: In all, 32 fractures in 26 subjects were investigated.
      No significant differences were found between surgical and conservative
      management for current pain (p = 0.984), current function (p = 0.170), or
      abnormality on CT (p = 0.173). However, surgically treated patients more often
      remained tender over the "N spot" (p = 0.005), even after returning to
      competition for two years or more. CONCLUSIONS: Surgical fixation of navicular
      stress fractures appears to be as effective as conservative management over the
      longer term. However, there remains a small but measurable degree of pain and
      loss of function over this period. The value of using "N spot" tenderness as the
      sole clinical predictor of treatment success requires further investigation, as
      some patients remained tender despite successful completion of treatment and
      return to competition.

PMID- 16611726
TI  - Glucocorticoid enhancement of memory requires arousal-induced noradrenergic
      activation in the basolateral amygdala.
AB  - Considerable evidence indicates that glucocorticoid hormones enhance the
      consolidation of long-term memories for emotionally arousing experiences but not
      that for less arousing or neutral information. However, previous studies have not
      determined the basis of such arousal-induced selectivity. Here we report the
      finding that endogenous noradrenergic activation of the basolateral complex of
      the amygdala (BLA) induced by emotional arousal is essential in enabling
      glucocorticoid memory enhancement. Corticosterone administered immediately after
      object recognition training enhanced 24-h memory of naive male rats but not that
      of rats previously habituated to the training context in order to reduce novelty
      induced emotional arousal. The beta-adrenoceptor antagonist propranolol
      administered either systemically or into the BLA blocked the corticosterone
      induced memory enhancement. Further, in habituated rats, corticosterone activated
      BLA neurons, as assessed by phosphorylated cAMP response element binding (pCREB)
      immunoreactivity levels, and enhanced memory only when norepinephrine release was
      stimulated by administration of the alpha(2)-adrenoceptor antagonist yohimbine.
      These findings strongly suggest that synergistic actions of glucocorticoids and
      emotional arousal-induced noradrenergic activation of the BLA constitute a neural
      mechanism by which glucocorticoids may selectively enhance memory consolidation
      for emotionally arousing experiences.

PMID- 16611727
TI  - Evidence that bovine forebrain embryonic zinc finger-like gene influences immune
      response associated with mastitis resistance.
AB  - Mastitis, a mammary gland inflammation in response to bacterial infection, is a
      major problem in the dairy industry. We found that cows susceptible to mastitis
      have a three-base insertion in a glycine-coding stretch of the gene for forebrain
      embryonic zinc finger-like (FEZL), a transcription factor with a role in neuronal
      development. Mastitis induces FEZL expression in mammary glands, and induced FEZL
      promotes expression of the axon-attracting molecule semaphorin 5A (SEMA5A)
      through a GCAG sequence. FEZL also induces SEMA5A expression in susceptible
      cattle but at a lower level than in resistant cattle. Enhanced SEMA5A induces
      expression of at least nine genes related to the host's immune response,
      including TNF-alpha and IL-8. We propose that susceptibility to mastitis results
      from an impaired immune response due to the lower transcription activity of
      susceptible FEZL. Our results provide an avenue to select for genetic improvement
      of resistance to mastitis and suggest that the FEZL-SEMA5A pathway might control
      both neuronal development and innate immunity.

PMID- 16611728
TI  - Cell-cell signaling in Xanthomonas campestris involves an HD-GYP domain protein
      that functions in cyclic di-GMP turnover.
AB  - HD-GYP is a protein domain of unknown biochemical function implicated in
      bacterial signaling and regulation. In the plant pathogen Xanthomonas campestris
      pv. campestris, the synthesis of virulence factors and dispersal of biofilms are
      positively controlled by a two-component signal transduction system comprising
      the HD-GYP domain regulatory protein RpfG and cognate sensor RpfC and by cell
      cell signaling mediated by the diffusible signal molecule DSF (diffusible signal
      factor). The RpfG/RpfC two-component system has been implicated in DSF perception
      and signal transduction. Here we show that the role of RpfG is to degrade the
      unusual nucleotide cyclic di-GMP, an activity associated with the HD-GYP domain.
      Mutation of the conserved H and D residues of the isolated HD-GYP domain resulted
      in loss of both the enzymatic activity against cyclic di-GMP and the regulatory
      activity in virulence factor synthesis. Two other protein domains, GGDEF and EAL,
      are already implicated in the synthesis and degradation respectively of cyclic di
      GMP. As with GGDEF and EAL domains, the HD-GYP domain is widely distributed in
      free-living bacteria and occurs in plant and animal pathogens, as well as
      beneficial symbionts and organisms associated with a range of environmental
      niches. Identification of the role of the HD-GYP domain thus increases our
      understanding of a signaling network whose importance to the lifestyle of diverse
      bacteria is now emerging.

PMID- 16611729
TI  - Cholesterol modification restricts the spread of Shh gradient in the limb bud.
AB  - Sonic hedgehog (Shh) produced in the zone of polarizing activity is the major
      determinant of anteroposterior development of the amniote limb. The mature and
      active Shh protein is cholesterol-modified at its C terminus, and the hydrophobic
      nature of the modification requires the function of Dispatched (mDispA), a seven
      pass transmembrane protein, for Shh release from its source. The current model
      suggests that the cholesterol moiety promotes the spread of Shh gradient in the
      limb bud. However, this model is inconsistent with findings in Drosophila and not
      in line with current thoughts on the role of the cholesterol moiety in Shh
      multimerization. Therefore, it remains unclear how the cholesterol moiety affects
      the postrelease extracellular behavior of Shh that relates to the shape of its
      activity gradient in responsive tissues. Here, we report functional analyses in
      mice showing that Shh lacking cholesterol modification (ShhN) has an increased
      propensity to spread long-distance, eliciting ectopic Shh pathway activation
      consistent with target gene expressions and modulating the level of Gli3
      processing in the anterior limb mesoderm. These molecular alterations are
      reflected in the mispatterning of digits in ShhN mutants. Additionally, we
      provide direct evidence for the long-distance movement of ShhN across the
      anteroposterior axis of the limb bud. Our findings suggest that the cholesterol
      moiety regulates the range and shape of the Shh morphogen gradient by restricting
      rather than promoting the postrelease spread of Shh across the limb bud during
      early development.

PMID- 16611730
TI  - Netrin-1 induces angiogenesis via a DCC-dependent ERK1/2-eNOS feed-forward
      mechanism.
AB  - Netrin-1 is critical for axonal pathfinding which shares similarities with
      formation of vascular network. Here we report that netrin-1 induction of
      angiogenesis is mediated by an increase in endothelial nitric oxide (NO*)
      production, which occurs via a DCC-dependent, ERK1/2-eNOS feed-forward mechanism.
      Exposure of mature aortic endothelial cells to netrin-1 resulted in a potent,
      dose-dependent increase in NO* production, detected by electron spin resonance.
      Scavenging NO* with 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO)
      abolished netrin-1 stimulated angiogenesis. Netrin-1-stimulated NO* production or
      angiogenesis was inhibited by DCC antibody, DCC small interfering RNA (siRNA),
      specific inhibitors (PD98059, U0126), or siRNAs for MEK1/2. PTIO attenuated
      ERK1/2 phosphorylation, indicating a feed-forward mechanism. Netrin-1 induced a
      time-dependent phosphorylation of eNOS(s1179, s116) and a rapid dephosphorylation
      of eNOS(t497). Only eNOS(s1179) was sensitive to U0126 or PTIO. These data
      characterized a mechanism whereby netrin-1 promotes angiogenesis, which may
      broadly relate to cardiovascular, neuronal and cancer physiology.

PMID- 16611731
TI  - Ubiquitylation of yeast proliferating cell nuclear antigen and its implications
      for translesion DNA synthesis.
AB  - The Rad6-Rad18 ubiquitin-conjugating enzyme complex promotes replication through
      DNA lesions by means of at least three different pathways: the DNA polymerase
      (Pol) eta- and zeta-dependent translesion DNA synthesis (TLS) and a Rad5-Mms2
      Ubc13-dependent pathway. In DNA-damaged yeast cells proliferating cell nuclear
      antigen (PCNA) becomes monoubiquitylated at the K164 residue, and genetic studies
      in yeast have indicated a requirement for this modification in TLS mediated by
      Poleta and Polzeta. To be able to decipher the role of PCNA monoubiquitylation in
      the TLS process, we have reconstituted this PCNA modification in vitro from
      purified yeast proteins. We show that, in addition to the requirement for Rad6
      Rad18, the reaction depends on the loading of the PCNA homotrimeric ring onto the
      DNA by replication factor C and that all three PCNA monomers become efficiently
      ubiquitylated. The availability of PCNA monoubiquitylated on all of its three
      monomers has enabled us to examine the effects of this PCNA modification on DNA
      synthesis by Pols delta, eta, zeta, and Rev1. Contrary to the prevailing ideas
      that presume a role for PCNA ubiquitylation in the disruption of Poldelta's
      binding to PCNA or in the enhancement of the binding affinity of the TLS Pols for
      PCNA, we find that PCNA ubiquitylation does not affect any of these processes.
      These observations lead us to suggest a role for PCNA monoubiquitylation in
      disrupting the PCNA binding of a protein(s) that otherwise is inhibitory to the
      binding of PCNA by TLS Pols.

PMID- 16611732
TI  - A pair-rule gene circuit defines segments sequentially in the short-germ insect
      Tribolium castaneum.
AB  - In Drosophila, a hierarchy of maternal, gap, pair-rule, and segment polarity gene
      interactions regulates virtually simultaneous blastoderm segmentation. For the
      last decade, studies have focused on revealing the extent to which Drosophila
      segmentation mechanisms are conserved in other arthropods where segments are
      added sequentially from anterior to posterior in a cellular environment. Despite
      our increased knowledge of individual segmentation genes, details of their
      interactions in non-Drosophilid insects are not well understood. We analyzed the
      Tribolium orthologs of Drosophila pair-rule genes, which display pair-rule
      expression patterns. Tribolium castaneum paired (Tc-prd) and sloppy-paired (Tc
      slp) genes produced pair-rule phenotypes when their transcripts were severely
      reduced by RNA interference. In contrast, similar analysis of T. castaneum even
      skipped (Tc-eve), runt (Tc-run), or odd-skipped (Tc-odd) genes produced severely
      truncated, almost completely asegmental phenotypes. Analysis of interactions
      between pair-rule components revealed that Tc-eve, Tc-run, and Tc-odd form a
      three-gene circuit to regulate one another as well as their downstream targets,
      Tc-prd and Tc-slp. The complement of primary pair-rule genes in Tribolium differs
      from Drosophila in that it includes Tc-odd but not Tc-hairy. This gene circuit
      defines segments sequentially in double segment periodicity. Furthermore, this
      single mechanism functions in the early blastoderm stage and subsequently during
      germ-band elongation. The periodicity of the Tribolium pair-rule gene
      interactions reveals components of the genetic hierarchy that are regulated in a
      repetitive circuit or clock-like mechanism. This pair-rule gene circuit provides
      insight into short-germ segmentation in Tribolium that may be more generally
      applicable to segmentation in other arthropods.

PMID- 16611734
TI  - Gene silencing of myostatin in differentiation of chicken embryonic myoblasts by
      small interfering RNA.
AB  - Myostatin (GDF-8) is known to negatively regulate skeletal muscle mass in
      myogenesis, but few studies have been conducted on the function of endogenous GDF
      8 in primary myoblasts. The present study was performed to assess the function of
      GDF-8 by RNA interference using primary culture of chicken embryonic myoblasts in
      which myoblasts were differentiated into myotubes. An active form of small
      interfering RNA (siRNA-1) targeting GDF-8 mRNA was introduced into myoblasts, and
      an inactive form of siRNA (siRNA-2) was used as a negative control. GDF-8
      transcript level was significantly reduced 24 h after the introduction of siRNA-1
      to 25% of the control, whereas a 52-kDa GDF-8 precursor was reduced to 45% of the
      control at 48 h. However, siRNA-2 did not decrease GDF-8 transcript level. When
      GDF-8-mediated promoter activity was measured chronologically by means of a
      pGL(CAGA)(10)-constructed luciferase reporter assay, a concomitant change in
      activity was initiated after 24 h. The activity rapidly decreased 30 h after
      siRNA-1 introduction, whereas high activity was maintained at 30-42 h in the
      control and siRNA-2-treated myoblasts. Myogenic factors such as MyoD and p21, but
      not myogenin, were altered after 72 h. Cell fusion of the multinucleated myotubes
      was delayed by the siRNA-1 introduction, and myotubes with aggregated nuclei were
      shorter and wider. These results strongly suggest that deficiency of GDF-8 delays
      cell differentiation and causes great alterations in the cellular morphology of
      chicken embryonic myotubes.

PMID- 16611733
TI  - Linkage of butterfly mate preference and wing color preference cue at the genomic
      location of wingless.
AB  - Sexual isolation is a critical form of reproductive isolation in the early stages
      of animal speciation, yet little is known about the genetic basis of divergent
      mate preferences and preference cues in young species. Heliconius butterflies,
      well known for their diversity of wing color patterns, mate assortatively as a
      result of divergence in male preference for wing patterns. Here we show that the
      specific cue used by Heliconius cydno and Heliconius pachinus males to recognize
      conspecific females is the color of patches on the wings. In addition, male mate
      preference segregates with forewing color in hybrids, indicating a genetic
      association between the loci responsible for preference and preference cue.
      Quantitative trait locus mapping places a preference locus coincident with the
      locus that determines forewing color, which itself is perfectly linked to the
      wing patterning candidate gene, wingless. Furthermore, yellow-colored males of
      the polymorphic race H. cydno alithea prefer to court yellow females, indicating
      that wing color and color preference are controlled by loci that are located in
      an inversion or are pleiotropic effects of a single locus. Tight genetic
      associations between preference and preference cue, although rare, make
      divergence and speciation particularly likely because the effects of natural and
      sexual selection on one trait are transferred to the other, leading to the
      coordinated evolution of mate recognition. This effect of linkage on divergence
      is especially important in Heliconius because differentiation of wing color
      patterns in the genus has been driven and maintained by natural selection for
      Mullerian mimicry.

PMID- 16611735
TI  - Release of iron from ferritin requires lysosomal activity.
AB  - How ferritin-Fe becomes available for cell functions is unknown. Our previous
      studies with rat hepatoma cells indicated ferritin had to be degraded to release
      its Fe. In these studies, we investigated whether this occurs in other cell types
      and whether lysosomes are required. Release of ferritin-Fe was induced with
      desferoxamine (DFO) in (59)Fe-preloaded hepatoma, Caco2, and erythroid K562 cells
      and measured by rocket immunoelectrophoresis and autoradiography. The half-lives
      for ferritin-(59)Fe and protein were parallel (23, 16, and 11 h for the hepatic,
      Caco2, and K562 cells, respectively). Co-treatment with 180 microM Fe, leupeptin,
      chymostatin, or chloroquine markedly decreased rates of ferritin-Fe release and
      ferritin degradation. Lactacystin had no effect except for a small one in
      erythroid cells. Fractionation of hepatoma cell lysates on iodixanol gradients
      showed rapid depletion of cytosolic ferritin by DFO treatment but no accumulation
      in lysosomes. We conclude that regardless of cell type, release of Fe from
      ferritin occurs mainly through lysosomal proteolysis.

PMID- 16611736
TI  - CGRP inhibits osteoprotegerin production in human osteoblast-like cells via
      cAMP/PKA-dependent pathway.
AB  - The osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand
      (RANKL)/receptor activator of nuclear factor-kappaB (RANK) system was evaluated
      as a potential target of CGRP anabolic activity on bone. Primary cultures of
      human osteoblast-like cells (hOB) express calcitonin receptor-like receptor (CLR)
      and receptor activity modifying protein 1, and, because CGRP stimulates cAMP (one
      of the modulators of OPG production in osteoblasts), it was investigated whether
      it affects OPG secretion and expression in hOB. CGRP treatment of hOB (10(-11) M
      10(-7) M) dose-dependently inhibited OPG secretion with an EC(50) of 1.08 x 10(
      10) M, and also decreased its expression. This action was blocked by the
      antagonist CGRP(8-37). Forskolin, a stimulator of cAMP production, and dibutyryl
      cAMP also reduced the production of OPG. CGRP (10(-8) M) enhanced protein kinase
      A (PKA) activity in hOB, and hOB exposure to the PKA inhibitor, H89 (2 x 10(-6)
      M), abolished the inhibitory effect of CGRP on OPG secretion. Conditioned media
      from CGRP-treated hOB increased the number of multinucleated tartrate-resistant
      acid phosphatase-positive cells and the secretion of cathepsin K in human
      peripheral blood mononuclear cells compared with the conditioned media of
      untreated hOB. These results show that the cAMP/PKA pathway is involved in the
      CGRP inhibition of OPG mRNA and protein secretion in hOB and that this effect
      favors osteoclastogenesis. CGRP could thus modulate the balance between
      osteoblast and osteoclast activity, participating in the fine tuning of all of
      the bone remodeling phases necessary for the subsequent anabolic effect.

PMID- 16611737
TI  - Translocon pores in the endoplasmic reticulum are permeable to small anions.
AB  - Contribution of translocon peptide channels to the permeation of low molecular
      mass anions was investigated in rat liver microsomes. Puromycin, which purges
      translocon pores of nascent polypeptides, creating additional empty pores, raised
      the microsomal uptake of radiolabeled UDP-glucuronic acid, while it did not
      increase the uptake of glucose-6-phosphate or glutathione. The role of translocon
      pores in the transport of small anions was also investigated by measuring the
      effect of puromycin on the activity of microsomal enzymes with intraluminal
      active sites. The mannose-6-phosphatase activity of glucose-6-phosphatase and the
      activity of UDP-glucuronosyltransferase were elevated upon addition of puromycin,
      but glucose-6-phosphatase and beta-glucuronidase activities were not changed. The
      increase in enzyme activities was due to a better access of the substrates to the
      luminal compartment rather than to activation of the enzymes. Antibody against
      Sec61 translocon component decreased the activity of UDP-glucuronosyltransferase
      and antagonized the effect of puromycin. Similarly, the addition of the puromycin
      antagonist anisomycin or treatments of microsomes, resulting in the release of
      attached ribosomes, prevented the puromycin-dependent increase in the activity.
      Mannose-6-phosphatase and UDP-glucuronosyltransferase activities of smooth
      microsomal vesicles showed higher basal latencies that were not affected by
      puromycin. In conclusion, translationally inactive, ribosome-bound translocons
      allow small anions to cross the endoplasmic reticulum membrane. This pathway can
      contribute to the nonspecific substrate supply of enzymes with intraluminal
      active centers.

PMID- 16611738
TI  - Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein
      tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway.
AB  - The multifunctional cell-surface protein dipeptidyl peptidase IV (DPPIV/CD26) is
      aberrantly expressed in many cancers and plays a key role in tumorigenesis and
      metastasis. Its diverse cellular roles include modulation of chemokine activity
      by cleaving dipeptides from the chemokine NH(2)-terminus, perturbation of
      extracellular nucleoside metabolism by binding the ecto-enzyme adenosine
      deaminase, and interaction with the extracellular matrix by binding proteins such
      as collagen and fibronectin. We have recently shown that DPPIV can be
      downregulated from the cell surface of HT-29 colorectal carcinoma cells by
      adenosine, which is a metabolite that becomes concentrated in the extracellular
      fluid of hypoxic solid tumors. Most of the known responses to adenosine are
      mediated through four different subtypes of G protein-coupled adenosine
      receptors: A(1), A(2A), A(2B), and A(3). We report here that adenosine
      downregulation of DPPIV from the surface of HT-29 cells occurs independently of
      these classic receptor subtypes, and is mediated by a novel cell-surface
      mechanism that induces an increase in protein tyrosine phosphatase activity. The
      increase in protein tyrosine phosphatase activity leads to a decrease in the
      tyrosine phosphorylation of ERK1/2 MAP kinase that in turn links to the decline
      in DPPIV mRNA and protein. The downregulation of DPPIV occurs independently of
      changes in the activities of protein kinases A or C, phosphatidylinositol 3
      kinase, other serine/threonine phosphatases, or the p38 or JNK MAP kinases. This
      novel action of adenosine has implications for our ability to manipulate
      adenosine-dependent events within the solid tumor microenvironment.

PMID- 16611739
TI  - ABCA1 mediates high-affinity uptake of 25-hydroxycholesterol by membrane vesicles
      and rapid efflux of oxysterol by intact cells.
AB  - ATP Binding Cassette (ABC) transporter, ABCA1, plays a pivotal role in reverse
      cholesterol transport by mediating the cellular efflux of phospholipid and
      cholesterol. Studies using intact cells strongly suggest that ABCA1 acts as a
      phospholipid floppase, but there has been no direct demonstration that the
      protein is a primary active sterol transporter. Using membrane vesicles from
      insect Sf21 cells, we found that ABCA1 mediated ATP-dependent uptake of [(3)H]25
      hydroxycholesterol with an apparent K(m) of 0.7 muM. Consistent with this high
      apparent affinity, expression of ABCA1 in human embryonic kidney cells both
      increased rapid efflux of 25-hydroxcholesterol and prevented oxysterol-mediated
      repression of low-density lipoprotein (LDL) receptor and 3-hydroxy-3
      methylglutaryl-coenzyme A (HMG-CoA) reductase mRNAs. Comparison of wild-type and
      ABCA1(-/-) murine fibroblasts indicates that 25-hydroxycholesterol is effluxed
      approximately 5-fold more rapidly by wild-type cells. In addition, the rate of
      efflux from the wild-type but not the ABCA1(-/-) fibroblasts is increased a
      further twofold by inducers of ABCA1 expression. Thus under the experimental
      conditions employed, endogenous ABCA1 is a major contributor to 25
      hydroxycholesterol efflux from wild-type fibroblasts. Evidence from in vitro
      studies indicates that oxysterols are potent inducers of genes involved in
      cellular cholesterol efflux and metabolism, including the ABCA1 gene, and
      repressors of genes involved in cholesterol synthesis or uptake. Our observations
      raise the possibility that efflux of oxysterols by ABCA1 could contribute to a
      homeostatic mechanism, which both attenuates oxysterol-induced expression of its
      cognate gene and alleviates repression of genes encoding proteins, such as HMG
      CoA reductase and LDL receptor.

PMID- 16611740
TI  - Denervation produces different single fiber phenotypes in fast- and slow-twitch
      hindlimb muscles of the rat.
AB  - Using a single, mechanically skinned fiber approach, we tested the hypothesis
      that denervation (0 to 50 days) of skeletal muscles that do not overlap in fiber
      type composition [extensor digitorum longus (EDL) and soleus (SOL) muscles of
      Long-Evans hooded rats] leads to development of different fiber phenotypes.
      Denervation (50 day) was accompanied by 1) a marked increase in the proportion of
      hybrid IIB/D fibers (EDL) and I/IIA fibers (SOL) from 30% to >75% in both
      muscles, and a corresponding decrease in the proportion of pure fibers expressing
      only one myosin heavy chain (MHC) isoform; 2) complex muscle- and fiber-type
      specific changes in sarcoplasmic reticulum Ca(2+)-loading level at physiological
      pCa approximately 7.1, with EDL fibers displaying more consistent changes than
      SOL fibers; 3) decrease by approximately 50% in specific force of all fiber
      types; 4) decrease in sensitivity to Ca(2+), particularly for SOL fibers (by
      approximately 40%); 5) decrease in the maximum steepness of the force-pCa curves,
      particularly for the hybrid I/IIA SOL fibers (by approximately 35%); and 6)
      increased occurrence of biphasic behavior with respect to Sr(2+) activation in
      SOL fibers, indicating the presence of both slow and fast troponin C isoforms. No
      fiber types common to the two muscles were detected at any time points (day 7,
      21, and 50) after denervation. The results provide strong evidence that not only
      neural factors, but also the intrinsic properties of a muscle fiber, influence
      the structural and functional properties of a particular muscle cell and explain
      important functional changes induced by denervation at both whole muscle and
      single cell levels.

PMID- 16611741
TI  - Cortactin has an essential and specific role in osteoclast actin assembly.
AB  - Osteoclasts are essential for bone dynamics and calcium homeostasis. The cells
      form a tight seal on the bone surface, onto which they secrete acid and proteases
      to resorb bone. The seal is associated with a ring of actin filaments. Cortactin,
      a c-Src substrate known to promote Arp2/3-mediated actin assembly in vitro, is
      expressed in osteoclasts and localizes to the sealing ring. To address the role
      of cortactin and actin assembly in osteoclasts, we depleted cortactin by RNA
      interference. Cortactin-depleted osteoclasts displayed a complete loss of bone
      resorption with no formation of sealing zones. On nonosteoid surfaces,
      osteoclasts flatten with a dynamic, actin-rich peripheral edge that contains
      podosomes, filopodia, and lamellipodia. Cortactin depletion led to a specific
      loss of podosomes, revealing a tight spatial compartmentalization of actin
      assembly. Podosome formation was restored in cortactin-depleted cells by
      expression of wild-type cortactin or a Src homology 3 point mutant of cortactin.
      In contrast, expression of a cortactin mutant lacking tyrosine residues
      phosphorylated by Src did not restore podosome formation. Cortactin was found to
      be an early component of the nascent podosome belt, along with dynamin,
      supporting a role for cortactin in actin assembly.

PMID- 16611742
TI  - Aip1 and cofilin promote rapid turnover of yeast actin patches and cables: a
      coordinated mechanism for severing and capping filaments.
AB  - Rapid turnover of actin structures is required for dynamic remodeling of the
      cytoskeleton and cell morphogenesis, but the mechanisms driving actin disassembly
      are poorly defined. Cofilin plays a central role in promoting actin turnover by
      severing/depolymerizing filaments. Here, we analyze the in vivo function of a
      ubiquitous actin-interacting protein, Aip1, suggested to work with cofilin. We
      provide the first demonstration that Aip1 promotes actin turnover in living
      cells. Further, we reveal an unanticipated role for Aip1 and cofilin in promoting
      rapid turnover of yeast actin cables, dynamic structures that are decorated and
      stabilized by tropomyosin. Through systematic mutagenesis of Aip1 surfaces, we
      identify two well-separated F-actin-binding sites, one of which contributes to
      actin filament binding and disassembly specifically in the presence of cofilin.
      We also observe a close correlation between mutations disrupting capping of
      severed filaments in vitro and reducing rates of actin turnover in vivo. We
      propose a model for balanced regulation of actin cable turnover, in which Aip1
      and cofilin function together to "prune" tropomyosin-decorated cables along their
      lengths. Consistent with this model, deletion of AIP1 rescues the temperature
      sensitive growth and loss of actin cable defects of tpm1Delta mutants.

PMID- 16611743
TI  - A discoidin domain receptor 1/SHP-2 signaling complex inhibits alpha2beta1
      integrin-mediated signal transducers and activators of transcription 1/3
      activation and cell migration.
AB  - Regulation of cell migration is an important step for the development of
      branching tubule morphogenesis in collagen gel. Here, we showed that discoidin
      domain receptor (DDR) 1a/b inhibited collagen-induced tyrosine phosphorylation of
      signal transducers and activators of transcription (Stat) 1/3 and cell migration
      triggered by alpha2beta1-integrin. Overexpression of DDR1a/b increased the
      interaction of DDR1 with SHP-2 and up-regulated the tyrosine phosphatase activity
      of SHP-2. Expression of catalytically inactive SHP-2 in DDR1-transfected cells
      restored the tyrosine phosphorylation of Stat3 and cell migration. We
      demonstrated that the Src homology-2 (SH2)-SH2 and phosphotyrosyl phosphatase
      (PTP) domains of SHP-2 were responsible for interaction with DDR1 and that both
      tyrosine phosphorylation sites 703 and 796 of DDR1 were essential for it to bind
      with SHP-2. Mutation of tyrosine 703 or 796 of DDR1 abolished the ability of DDR1
      to inhibit the tyrosine phosphorylation of Stat1 and Stat3 and restored collagen
      induced cell migration and hepatocyte growth factor-induced branching
      tubulogenesis in collagen gel. Together, these results demonstrate that SHP-2 is
      required for the DDR1-induced suppression of Stat1 and Stat3 tyrosine
      phosphorylation, cell migration, and branching tubulogenesis.

PMID- 16611744
TI  - PAK1 and aPKCzeta regulate myosin II-B phosphorylation: a novel signaling pathway
      regulating filament assembly.
AB  - Many signaling pathways regulate the function of the cellular cytoskeleton. Yet
      we know very little about the proteins involved in the cross-talk between the
      signaling and the cytoskeletal systems. Here we show that myosin II-B, an
      important cytoskeletal protein, resides in a complex with p21-activated kinase 1
      (PAK1) and atypical protein kinase C (PKC) zeta (aPKCzeta) and that the
      interaction between these proteins is EGF-dependent. We further show that PAK1 is
      involved in aPKCzeta phosphorylation and that aPKCzeta phosphorylates myosin II-B
      directly on a specific serine residue in an EGF-dependent manner. This latter
      phosphorylation is specific to isoform B of myosin II, and it leads to slower
      filament assembly of myosin II-B. Furthermore, a decrease in aPKCzeta expression
      in the cells alters myosin II-B cellular organization. Our finding of a new
      signaling pathway involving PAK1, aPKCzeta, and myosin II-B, which is implicated
      in myosin II-B filament assembly and cellular organization, provides an important
      link between the signaling system and cytoskeletal dynamics.

PMID- 16611745
TI  - Yeast Gcn4p stabilization is initiated by the dissociation of the nuclear
      Pho85p/Pcl5p complex.
AB  - Protein stability of the c-jun-like yeast bZIP transcriptional activator Gcn4p is
      exclusively controlled in the yeast nucleus. Phosphorylation by the nuclear
      Pho85p cyclin-dependent protein kinase, a functional homolog of mammalian Cdk5,
      initiates the Gcn4p degradation pathway in complex with the cyclin Pcl5p. We show
      that the initial step in Gcn4p stabilization is the dissociation of the
      Pho85p/Pcl5p complex. Pcl7p, another nuclear and constantly present cyclin, is
      required for Gcn4p stabilization and is able to associate to Pho85p independently
      of the activity of the Gcn4p degradation pathway. In addition, the nuclear cyclin
      dependent Pho85p kinase inhibitor Pho81p is required for Gcn4p stabilization.
      Pho81p only interacts with Pcl5p when Gcn4p is rapidly degraded but
      constitutively interacts with Pcl7p. Our data suggest that Pcl7p and Pho81p are
      antagonists of the Pho85p/Pcl5p complex formation in a yet unknown way, which are
      specifically required for Gcn4p stabilization. We suggest that dissociation of
      the Pho85p/Pcl5p complex as initial step in Gcn4p stabilization is a prerequisite
      for a shift of equilibrium to an increased amount of the Pho85p/Pcl7p complexes
      and subsequently results in decreased Gcn4p phosphorylation and therefore
      increased stability of the transcription factor.

PMID- 16611746
TI  - The rab exchange factor Sec2p reversibly associates with the exocyst.
AB  - Activation of the rab GTPase, Sec4p, by its exchange factor, Sec2p, is needed for
      polarized transport of secretory vesicles to exocytic sites and for exocytosis. A
      small region in the C-terminal half of Sec2p regulates its localization. Loss of
      this region results in temperature-sensitive growth and the depolarized
      accumulation of secretory vesicles. Here, we show that Sec2p associates with the
      exocyst, an octameric effector of Sec4p involved in tethering secretory vesicles
      to the plasma membrane. Specifically, the exocyst subunit Sec15p directly
      interacts with Sec2p. This interaction normally occurs on secretory vesicles and
      serves to couple nucleotide exchange on Sec4p to the recruitment of the Sec4p
      effector. The mislocalization of Sec2p mutants correlates with dramatically
      enhanced binding to the exocyst complex. We propose that Sec2p is normally
      released from the exocyst after vesicle tethering so that it can recycle onto a
      new round of vesicles. The mislocalization of Sec2p mutants results from a
      failure to be released from Sec15p, blocking this recycling pathway.

PMID- 16611747
TI  - Members of the NIMA-related kinase family promote disassembly of cilia by
      multiple mechanisms.
AB  - The genome of Tetrahymena thermophila contains 39 loci encoding NIMA-related
      kinases (NRKs), an extraordinarily large number for a unicellular organism.
      Evolutionary analyses grouped these sequences into several subfamilies, some of
      which have orthologues in animals, whereas others are protist specific. When
      overproduced, NRKs of three subfamilies caused rapid shortening of cilia.
      Ultrastructural studies revealed that each NRK triggered ciliary resorption by a
      distinct mechanism that involved preferential depolymerization of a subset of
      axonemal microtubules, at either the distal or proximal end. Overexpression of a
      kinase-inactive variant caused lengthening of cilia, indicating that constitutive
      NRK-mediated resorption regulates the length of cilia. Each NRK preferentially
      resorbed a distinct subset of cilia, depending on the location along the
      anteroposterior axis. We also show that normal Tetrahymena cells maintain unequal
      length cilia. We propose that ciliates used a large number of NRK paralogues to
      differentially regulate the length of specific subsets of cilia in the same cell.

PMID- 16611748
TI  - CDKL5 mutations cause infantile spasms, early onset seizures, and severe mental
      retardation in female patients.
AB  - OBJECTIVE: To determine the frequency of mutations in CDKL5 in both male and
      female patients with infantile spasms or early onset epilepsy of unknown cause,
      and to consider whether the breadth of the reported phenotype would be extended
      by studying a different patient group. METHODS: Two groups of patients were
      investigated for CDKL5 mutations. Group 1 comprised 73 patients (57 female, 16
      male) referred to Cardiff for CDKL5 analysis, of whom 49 (42 female, 7 male) had
      epileptic seizure onset in the first six months of life. Group 2 comprised 26
      patients (11 female, 15 male) with infantile spasms previously recruited to a
      clinical trial, the UK Infantile Spasms Study. Where a likely pathogenic mutation
      was identified, further clinical data were reviewed. RESULTS: Seven likely
      pathogenic mutations were found among female patients from group 1 with epileptic
      seizure onset in the first six months of life, accounting for seven of the 42 in
      this group (17%). No mutations other than the already published mutation were
      found in female patients from group 2, or in any male patient from either study
      group. All patients with mutations had early signs of developmental delay and
      most had made little developmental progress. Further clinical information was
      available for six patients: autistic features and tactile hypersensitivity were
      common but only one had suggestive Rett-like features. All had a severe epileptic
      seizure disorder, all but one of whom had myoclonic jerks. The EEG showed focal
      or generalised changes and in those with infantile spasms, hypsarrhythmia. Slow
      frequencies were seen frequently with a frontal or fronto-temporal predominance
      and high amplitudes. CONCLUSIONS: The spectrum of the epileptic seizure disorder,
      and associated EEG changes, in those with CDKL5 mutations is broader than
      previously reported. CDKL5 mutations are a significant cause of infantile spasms
      and early epileptic seizures in female patients, and of a later intractable
      seizure disorder, irrespective of whether they have suspected Rett syndrome.
      Analysis should be considered in these patients in the clinical setting.

PMID- 16611749
TI  - Predicting disease genes using protein-protein interactions.
AB  - BACKGROUND: The responsible genes have not yet been identified for many
      genetically mapped disease loci. Physically interacting proteins tend to be
      involved in the same cellular process, and mutations in their genes may lead to
      similar disease phenotypes. OBJECTIVE: To investigate whether protein-protein
      interactions can predict genes for genetically heterogeneous diseases. METHODS:
      72,940 protein-protein interactions between 10,894 human proteins were used to
      search 432 loci for candidate disease genes representing 383 genetically
      heterogeneous hereditary diseases. For each disease, the protein interaction
      partners of its known causative genes were compared with the disease associated
      loci lacking identified causative genes. Interaction partners located within such
      loci were considered candidate disease gene predictions. Prediction accuracy was
      tested using a benchmark set of known disease genes. RESULTS: Almost 300
      candidate disease gene predictions were made. Some of these have since been
      confirmed. On average, 10% or more are expected to be genuine disease genes,
      representing a 10-fold enrichment compared with positional information only.
      Examples of interesting candidates are AKAP6 for arrythmogenic right ventricular
      dysplasia 3 and SYN3 for familial partial epilepsy with variable foci.
      CONCLUSIONS: Exploiting protein-protein interactions can greatly increase the
      likelihood of finding positional candidate disease genes. When applied on a large
      scale they can lead to novel candidate gene predictions.

PMID- 16611751
TI  - Packing density in coiling of small intracranial aneurysms.

PMID- 16611750
TI  - Polymorphisms in the VKORC1 gene are strongly associated with warfarin dosage
      requirements in patients receiving anticoagulation.
AB  - BACKGROUND: Warfarin is a mainstay of therapy for conditions associated with an
      increased risk of thromboembolic events. However, the use of this common agent is
      fraught with complications and little is known regarding inter-individual
      variation in warfarin response. OBJECTIVE: We tested for association between
      single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 and average weekly
      warfarin dose required to maintain patients at their desired anticoagulation
      target. METHODS: The sample consisted of 93 European-American patients from
      anticoagulation clinics at the University of North Carolina at Chapel Hill. Data
      on mean weekly warfarin dose were collected over a mean treatment period of 20.6
      months. ANCOVA models were used and haplotype analysis was performed. RESULTS:
      Three of six VKORC1 SNPs were found to be very strongly associated with the
      average warfarin dose required to achieve the target international normalised
      ratio (INR; p<0.0001). The mean weekly dose by genotype ranged from approximately
      27 to 47 mg. There was no evidence for an association between either of the two
      CYP2C9 polymorphisms studied, CYP2C9*2 and CYP2C9*3. CYP2C9*3 was significantly
      (p = 0.05) associated with average warfarin dosage after adjustment for
      VKORC1*1173. CONCLUSIONS: These results are of considerable clinical interest and
      confirm recently published results regarding the role of these two genes in
      modifying warfarin metabolism and maintenance dosage. The consistent findings
      regarding the role of VKORC1 and CYP2C9 in warfarin metabolism and maintenance
      dosage represent a clinically useful proof of principal for the use of
      pharmacogenomic information in medicine and may lead to improved understanding of
      warfarin's actions.

PMID- 16611752
TI  - Experimental MR imaging of the rabbit brain: How to perform it better.

PMID- 16611753
TI  - Subarachnoid hemorrhage due to isolated spinal arteries: Rare cases with
      controversy about the treatment strategy.

PMID- 16611754
TI  - Imaging-guided acute ischemic stroke therapy: From "time is brain" to "physiology
      is brain".
AB  - The number of potential patients who are actually treated for acute ischemic
      stroke is disappointingly low, and effective treatments are making a minor impact
      on this major public health problem. Imaging is not regularly used to identify
      the ischemic penumbra, a key concept in stroke physiology, though it is capable
      of doing so in a clinically relevant manner. Evidence is accumulating that
      identification of the ischemic penumbra and making treatment decisions on the
      basis of its presence provide substantial benefit to patient outcomes. Moreover,
      the same studies suggest that an unexpectedly large proportion of patients are
      suitable for therapy well past the traditional time windows because of the
      existence of a substantial ischemic penumbra. Modern MR imaging and CT systems,
      now widely available, are capable of answering the most relevant physiologic
      questions in acute ischemic stroke. This capability presents new opportunities
      and responsibilities to neuroradiologists to make appropriate imaging readily
      available and to have the imaging data rapidly processed and interpreted. In this
      article, acute ischemic stroke therapy, including the role of imaging in current
      medical practice, is reviewed, and an evidence-based alternative to contemporary
      acute ischemic stroke therapy is suggested.

PMID- 16611755
TI  - A longitudinal immunohistochemical study of the healing of experimental aneurysms
      after embolization with platinum coils.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to probe the cellular
      mechanism of healing in aneurysms after platinum coil embolization, by using
      multiple special stains and immunolabels. METHODS: Elastase-induced aneurysms
      were created and embolized in 28 rabbits. Aneurysms were excised between 2 and 24
      weeks after embolization. Specimens were embedded in paraffin, sectioned, and
      stained with hematoxylin-eosin, Masson trichrome, and multiple immunostains.
      RESULTS: At 2 weeks, peripheral sparse spindle-nucleated cells were positive for
      alpha-smooth muscle actin (SMA), myosin, and vimentin, indicating myofibroblastic
      differentiation. At 4 weeks, all spindle-nucleated cells in the aneurysm were
      positive for SMA, myosin, desmin, and vimentin. Ten weeks after embolization,
      positive immunohistochemical staining in the cells populating the aneurysm
      significantly decreased. Mean positive SMA cells, per high-powered field were 5
      +/- 3, 45 +/- 9, 10 +/- 5, 0 +/- 0, and 0 +/- 0 at 2, 4, 10, 16, and 24 weeks,
      respectively. Findings of a Kruskal-Wallis test showed these data to be
      significantly different (P =.0001). Post hoc tests revealed significantly greater
      amounts of SMA-positive staining in the cells at 4 weeks compared with those at
      2, 10, 16, and 24 weeks (P < .05). In addition, the 10-week group had
      significantly more positive cells than the 16- and 24-week groups (P < .05).
      There was a 78% decrease in apoptotic cells between 4 (37 +/- 11) and 10 weeks (8
      +/- 4) after implantation. Apoptotic cells were completely absent beyond 10
      weeks. CONCLUSION: Aneurysm healing, in response to platinum coil embolization,
      appeared to progress through the stages of thrombus formation, granulated tissue
      organization, and loose connective tissue formation. Myofibroblasts, the key
      cellular component involved in healing, appeared within the aneurysm early. They
      progressively reduced in number with time and finally disappeared through the
      mechanism of apoptosis.

PMID- 16611756
TI  - Radiation exposure to the primary operator during endovascular surgical
      neuroradiology procedures.
AB  - Endovascular surgical neuroradiologists can receive a substantial amount of
      occupational radiation exposure. We evaluated the amount of radiation exposure
      that results from the practice of performing hand injections during digital
      subtraction angiography (DSA). The primary operator can significantly decrease
      the radiation dose by leaving the room for DSA procedures. However, the total
      radiation dose for the primary operator is relatively low and is certainly within
      allowable regulatory limits when extrapolated to a yearly dose.

PMID- 16611757
TI  - Follow-up of intracranial aneurysms selectively treated with coils: Prospective
      evaluation of contrast-enhanced MR angiography.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to determine the feasibility
      and usefulness of contrast-enhanced MR angiography (CE-MRA) for the follow-up of
      intracranial aneurysms treated with detachable coils, by comparing CE-MRA with
      digital subtraction angiography (DSA) and 3D time-of- flight (TOF) MRA. METHODS:
      Thirty-two patients with 42 treated aneurysms were included in the study; 6 had
      been treated for multiple aneurysms. All MRAs were performed with a 1.5T unit
      within 48 hours of DSA. We performed 2 types of acquisition: a 3D TOF sequence
      and CE-MRA. Twenty-eight patients were included 1 year after endovascular
      treatment, and 4 patients, after 3 years or more. DSA was the technique of
      reference for the detection of a residual neck or residual aneurysm. RESULTS:
      Compared with DSA, the sensitivity of MRA was good. For the detection of residual
      neck, there was no significant difference between the results of 3D TOF MRA
      (sensitivity, 75%-87.5%; specificity, 92.9%, according to both readers) and CE
      MRA (sensitivity, 75%-82.1%; specificity, 85.7%-92.9%). For the detection of
      residual aneurysm, sensitivity and specificity of both techniques were the same,
      respectively 80%-100% and 97.3%-100%. Therefore, CE-MRA was not better than 3D
      TOF MRA for the detection of residual neck or residual aneurysm. For large
      treated aneurysms, there was no difference between decisions regarding further
      therapy after CE and 3D TOF MRA, even though CE-MRA with a short echotime and
      enhancement gave fewer artifacts and better visualization of recanalization than
      3D TOF MRA. The interpretation of transverse source images and the detection of
      coil mesh packing seemed easier with 3D TOF imaging. CONCLUSION: This prospective
      study did not show that CE-MRA was significantly better than 3D TOF MRA for
      depicting aneurysm or neck remnants after selective endovascular treatment using
      coils. For aneurysms treated with coils, 3D TOF MRA seems a valid and useful
      technique for the follow-up of coiled aneurysms.

PMID- 16611758
TI  - Transarterial coil embolization of the venous component of aggressive type 4
      dural arteriovenous fistulas.
AB  - We report 2 patients with aggressive intracranial dural arteriovenous fistulae
      that were repaired via percutaneous, transarterial coil embolization of the
      venous outlets.

PMID- 16611759
TI  - Diffusion-weighted MR imaging in carotid angioplasty and stenting with protection
      by the reversed carotid arterial flow.
AB  - BACKGROUND AND PURPOSE: Distal embolism during carotid angioplasty with stent
      (CAS) can be protected by a flow-reversal device. Diffusion-weighted MR imaging
      was used to evaluate this protective procedure and perform a comparison with the
      control. METHODS: Cases of CAS with protection procedures were included in this
      study. Sixty-five men (68 procedures) and 5 women (5 procedures), with an average
      age of 68.8 years, having severe carotid stenosis were treated in our department
      between 2002 and 2004. Eleven cases were treated with the Parodi Anti-Emboli
      System, with which the internal carotid blood flow is reversed by simultaneous
      occlusion of the proximal common carotid artery and external carotid artery.
      Diffusion-weighted MR imaging was performed within 1-3 days after CAS. As
      controls, data from diffusion-weighted MR imaging in 26 patients who had
      diagnostic angiography were included. RESULTS: Diffusion-weighted MR imaging in
      diagnostic angiography showed 11.5% appearance of ischemic spots after
      procedures. In the Parodi Anti-Emboli System, this value was 18.2%. In the CAS
      group, ischemic lesions appeared only in the hemisphere ipsilateral to carotid
      stenosis. There were no ischemic lesions in the opposite carotid or
      vertebrobasilar territory. The appearance rate of new ischemic spots was not
      significantly different between the control group and the group of CAS with
      Parodi Anti-Emboli System (chi2 test, P = .6227, Fisher exact method).
      CONCLUSIONS: Protection results obtained with the Parodi system were excellent
      and comparable with conventional angiography.

PMID- 16611760
TI  - Multicenter evaluation of a self-expanding carotid stent system with distal
      protection in the treatment of carotid stenosis.
AB  - PURPOSE: Carotid artery stent placement may be limited by the embolization of
      atheromatous material. We evaluated the safety and feasibility of the Medtronic
      Self-Expanding Carotid Stent (Exponent) in combination with the Medtronic
      Interceptor Carotid Filter System for the treatment of carotid stenosis among
      patients at high risk for carotid endarterectomy. METHODS: Patients at high risk
      for carotid endarterectomy but amenable to percutaneous treatment with stent
      placement were enrolled. Clinical follow-up was performed at 30 days and 6 and 12
      months postprocedure. The National Institutes of Health Stroke Scale was assessed
      before and within 3 days postprocedure and at 30 days and 6 months postprocedure.
      Angiography was performed pre- and postprocedure, and carotid duplex scans were
      performed at baseline and at 30 days and 6 months. RESULTS: Fifty-two carotid
      procedures were performed in 51 patients (mean age, 69 years; 84% of patients
      were men). The major adverse event (MAE) rate (death, stroke, and myocardial
      infarction [MI]) at 30 days was 5.9%: 2 strokes and a single death from
      periprocedural MI. MAE rates after 6 and 12 months were 5.9% and 11.8%,
      respectively. The delivery success rate was 94.2% (49/52) for the Interceptor
      Filter System and 95.9% (47/49) for the Exponent Stent. The mean diameter
      stenosis of the target lesion was reduced from 62.4% preprocedure to 21.2%
      postprocedure. CONCLUSION: High delivery success rates were achieved with a low
      rate of MAE (death, stroke, or MI) in a high-risk population. Treatment of
      carotid artery disease with the Exponent Carotid Stent combined with distal
      protection from the Interceptor Filter System is effective and safe.

PMID- 16611761
TI  - Giant serpentine aneurysm with acute spontaneous complete thrombosis.
AB  - We report a case of a giant serpentine aneurysm (GSA) of the middle cerebral
      artery (MCA) that underwent complete spontaneous thrombosis after angiography.
      The patient was a 24-year-old man who had an acute headache. CT and MR
      examinations revealed a large partially thrombosed aneurysm of the MCA with
      residual flow in the artery. Angiography demonstrated a GSA arising from the left
      MCA. Thirteen days later, a second angiography showed complete thrombosis of the
      aneurysm.

PMID- 16611762
TI  - Intra-arterial reteplase compared to urokinase for thrombolytic recanalization in
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Reteplase (RP) and urokinase (UK) are being used "off
      label" to treat acute ischemic stroke. The safety and efficacy of intra-arterial
      RP or UK in the treatment of acute ischemic stroke, however, has yet to be
      proved. We aim to evaluate the safety and efficacy of RP compared with UK in
      acute ischemic stroke patients with large vessel occlusion. METHODS:
      Retrospective analysis was conducted of cases from a prospectively collected
      stroke data base on consecutive acute ischemic stroke patients with large vessel
      occlusion by digital subtraction angiography treated with intra-arterial RP or
      UK. Thrombolytic dosage, recanalization rate, intracerebral hemorrhage (ICH),
      mortality, and outcome were determined. RESULTS: Thirty-three patients received
      RP and 22 received UK (mean doses, 2.5 +/- 1.4 mg and 690,000 +/- 562,000 U,
      respectively). Vascular occlusions included 9 basilar arteries (BAs), 7 internal
      carotid arteries (ICAs), and 17 middle cerebral arteries (MCAs) with RP and 9
      BAs, 4 ICAs, and 9 MCAs with UK. Median baseline National Institutes of Health
      Stroke Scales were as follows: 16 (range, 5-25; 81% > or = 10) with RP and 17
      (range, 6-38; 85% > or =10) with UK. Mean time from symptom onset to thrombolytic
      initiation: 333 +/- 230 minutes with RP and 343 +/- 169 minutes with UK.
      Recanalization rates were as follows: 82% with RP and 64% with UK (P = .13).
      Symptomatic ICH rates were as follows: 12% with RP and 4.5% with UK (P = .50).
      The mortality rate was 24% with RP and 27% with UK (P = .8). CONCLUSION: Although
      limited in statistical power, our study suggests that, although IA thrombolysis
      with RP shows a trend for higher recanalization rates and hemorrhage rates, IA
      thrombolysis with RP is not significantly different in recanalization, outcome,
      mortality, and ICH compared with that of UK or rates reported with IA pro-UK.

PMID- 16611763
TI  - Microcatheter navigation and thrombolysis in acute symptomatic cervical internal
      carotid occlusion.
AB  - BACKGROUND AND PURPOSE: The treatment of acute stroke distal to an occluded
      cervical internal carotid artery (ICA) presents a challenge. We report our
      results of endovascular therapy in 7 patients presenting with acute symptomatic
      cervical ICA occlusion. PATIENTS AND TECHNIQUES: Among patients presenting with
      acute stroke at our institution from June 2001 to June 2005, we retrospectively
      identified 7 patients who underwent endovascular therapy of acute cervical ICA
      occlusion. The techniques used for vessel recanalization were analyzed.
      Postprocedure CT scans were reviewed for hemorrhage. The clinical outcomes were
      assessed by using the modified Rankin scale (mRS) with good outcomes assigned
      scores of < or =2. RESULTS: All 7 patients revealed cervical ICA occlusion, with
      additional intracranial thrombus in 6 of the 7 patients. In all patients, a
      guiding catheter was placed in the ipsilateral common carotid artery proximal to
      the occlusion and a microcatheter advanced through the ICA clot to deliver intra
      arterial (IA) tissue plasminogen activator (in 6 patients, the microcatheter was
      also advanced intracranially for thrombolysis). Successful recanalization of the
      occluded ICA was achieved in 6 patients. In 3 patients, balloon angioplasty and
      stent placement of the cervical ICA was also performed. Follow-up CT in 6
      patients showed small basal ganglia infarcts in 4, patchy parietal infarcts in
      one, and frontal lobe hematoma in one patient. At 1 month after the procedure, 5
      patients had good clinical outcomes (mRS of 0 in 4 patients and 1 in one
      patient). CONCLUSION: Performance of IA thrombolysis by passing a microcatheter
      through an acutely occluded internal carotid artery may be an effective therapy
      in acute stroke.

PMID- 16611764
TI  - Protective effect of agmatine on a reperfusion model after transient cerebral
      ischemia: Temporal evolution on perfusion MR imaging and histopathologic
      findings.
AB  - BACKGROUND AND PURPOSE: The goal of thrombolytic therapy in patients with acute
      ischemic stroke is early recanalization, but this may result in delayed
      reperfusion injury. The purpose of this study was to evaluate the neuroprotective
      effect of agmatine in a transient ischemic cat model by using MR perfusion
      imaging and histopathologic analyses. METHOD: One-hour temporary occlusion of the
      left middle cerebral artery of cats was performed in the control ischemia group
      (n = 10), and 100 mg/kg of agmatine was intravenously injected immediately after
      recanalization in the agmatine-treated group (n = 15). MR imaging was performed
      at 1, 24, and 48 hours after recanalization, and the perfusion patterns were
      investigated. Terminal-deoxynucleotidyl transferase mediated nick and end
      labeling (TUNEL) and hematoxylin-eosin (H&E) stainings were performed at the
      corresponding sections. RESULTS: In the control ischemia group, the number of
      TUNEL-positive cells was significantly increased in the areas with reperfusion
      hyperemia (P < .05). In the agmatine-treated group, no significant increase in
      the number of TUNEL-positive cells was noted in the areas of reperfusion
      hyperemia. The difference in the number of TUNEL-positive cells between the
      control ischemia and agmatine-treated group in the areas of reperfusion hyperemia
      was significant (P < .05). The total number of TUNEL-positive cells and the area
      of severe ischemic neuronal damage on H&E stain were also significantly
      attenuated in the agmatine-treated cats compared with the control ischemia cats
      (P < .05). CONCLUSION: Our results suggest that agmatine has neuroprotective
      effects against reperfusion injury and ischemia.

PMID- 16611765
TI  - Diffusion tensor imaging of tract involvement in children with pontine tumors.
AB  - BACKGROUND AND PURPOSE: Conventional MR imaging permits subcategorization of
      brain stem tumors by location and focality; however, assessment of white matter
      tract involvement by tumor is limited. Diffusion tensor imaging (DTI) is a
      promising method for visualizing white matter tract tumor involvement
      supratentorially. We investigated the ability of DTI to visualize and quantify
      white matter tract involvement in pontine tumors. METHODS AND MATERIALS: DTI data
      (echo-planar, 1.5T) were retrospectively analyzed in 7 patients with pontine
      tumors (6 diffuse, 1 focal), 4 patient controls, and 5 normal volunteers.
      Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were
      calculated from the diffusion tensor in 6 regions of interest: bilateral
      corticospinal tracts, transverse pontine fibers, and medial lemnisci.
      Relationships between FA and ADC values and results of the neurologic
      examinations were evaluated. RESULTS: The corticospinal tracts and transverse
      pontine fibers were affected more often than the medial lemnisci. The DTI
      parameters (FA and ADC) were significantly altered in all tracts of patients with
      pontine tumors (P < .05), compared with those values in the control groups. A
      marginally significant (P = .057) association was seen between the severity of
      cranial nerve deficit and decreased FA. CONCLUSION: DTI provided superior
      visualization and quantification of tumor involvement in motor, sensory, and
      transverse pontine tracts, compared with information provided by conventional MR
      imaging. Thus, DTI may be a sensitive measure of tract invasion. Further
      prospective studies are warranted to assess the ability of DTI to delineate tumor
      focality and improve risk stratification in children with pontine tumors.

PMID- 16611766
TI  - Hypothalamic hamartomas: Correlation of MR imaging and spectroscopic findings
      with tumor glial content.
AB  - BACKGROUND AND PURPOSE: There is variability in the literature concerning the
      appearance and histology of hypothalamic hamartomas. This study correlates the MR
      imaging and proton MR spectroscopic properties of hypothalamic hamartomas with
      histopathologic findings. METHODS: Studies were performed with 3T and 1.5T
      scanners. Single voxel hamartoma spectra were acquired by using short-echo-time
      point-resolved spectroscopy sequences (PRESS). 2D PRESS chemical shift imaging
      (CSI) spectroscopic sequences were also obtained for comparison of tumor-derived
      spectra with normal gray matter of the amygdala. Sequences were used to compare
      choline (Cho), N-acetylaspartate (NAA), and myoinositol (mI) resonances by using
      a creatine (Cr) reference. Spectral ratios and T2 signal intensity ratios of the
      hamartomas were then compared with histopathologic findings. RESULTS: Data from
      single voxel spectroscopic sequences demonstrated a statistically significant
      decrease in NAA/Cr and an increase in mI/Cr ratios in tumor tissue when compared
      with values in normal gray matter of the amygdala. In addition, Cho/Cr ratios
      were also increased when compared with those in normal gray matter controls.
      Among the 14 hamartomas sampled, a spectrum of increased mI/Cr ratios was seen.
      Those tumors with markedly elevated mI/Cr demonstrated an increased glial
      component when compared with the remaining tumors. Increased glial component was
      also found to have a positive correlation with hyperintensity of lesions on T2
      weighted images. CONCLUSION: We have identified a correlation between the
      glial/neuronal fraction as determined by histopathology and MR spectral and T2
      hyperintensity variations among hypothalamic hamartomas.

PMID- 16611767
TI  - How depth of anesthesia influences the blood oxygenation level-dependent signal
      from the visual cortex of children.
AB  - BACKGROUND AND PURPOSE: Functional MR imaging (fMRI) is playing an important role
      in investigations of cortical development and maturation. Functional MR imaging
      in young children or infants frequently involves measuring a clinical population
      under sedation or anesthesia. We examined the effect of depth of anesthesia on
      the extent and amplitude of the blood oxygen level-dependent (BOLD) response.
      METHOD: We performed BOLD-based fMRI on a visual stimulus flickering at 8 Hz at
      sevoflurane concentrations of 0.5 minimum alveolar concentration (MAC), 0.75 MAC,
      and 1.0 MAC, on 16 children at least 5 years of age. We determined the extent of
      activation by counting the number of activated voxels and assessed the change in
      the local deoxyhemoglobin concentration by comparing DeltaR2*. RESULTS: The
      number of activated voxels of the positive BOLD response was higher at 0.75 MAC
      than at 0.5 MAC or 1.0 MAC. The magnitude of their mean DeltaR2* steadily
      declined as the level of sevoflurane was increased from 0.5 MAC to 1.0 MAC. The
      extent of activation of the negative BOLD response declined progressively from
      0.5 MAC to 1.0 MAC. The magnitude of their mean amplitude of the DeltaR2* did not
      change with sevoflurane concentrations. The change in the extent of activation
      and the magnitude of DeltaR2* when the concentration of sevoflurane increased
      from 0.5 MAC to 0.75 MAC was due to its vasodilative property. The change in the
      extent of activation and the amplitude of DeltaR2* following the increase in the
      concentration of sevoflurane from 0.75 MAC and 1.0 MAC was due to its anesthetic
      property. This was the case for both the positive and negative BOLD response.
      CONCLUSIONS: Careful adjustment of anesthetic depth can be used advantageously
      when performing BOLD-based fMRI measurements in children.

PMID- 16611768
TI  - Longitudinal MR spectroscopic imaging of pediatric diffuse pontine tumors to
      assess tumor aggression and progression.
AB  - Two pediatric patients with diffuse pontine tumors underwent MR spectroscopic
      imaging pre- and postradiation. Choline/creatine (Cho/Cr) and Cho/N
      acetylaspartate (NAA) ratios were elevated before treatment, with no MR imaging
      contrast enhancement. These ratios were further elevated at 2 posttreatment
      follow-up studies, despite signs of excellent clinical improvement at initial
      follow-up. This study suggests that MR spectroscopic imaging is more specific in
      assessing the aggressiveness of diffuse pontine tumors than conventional MR
      imaging and can serve as a valuable tool in early prognostication.

PMID- 16611769
TI  - Spinal hamartoma in a neonate: Unusual presentation and MR imaging findings.
AB  - We report an extremely rare case of a congenital spinal cord hamartoma in a male
      neonate who presented with upper extremity weakness and a port wine stain on the
      right upper extremity and chest. MR imaging findings are described, and the
      importance of localizing the lesion in the spinal canal with respect to the dura
      and its impact on neurosurgical management is stressed.

PMID- 16611770
TI  - Multidetector CT angiography in diagnosing type I and type IVA spinal vascular
      malformations.
AB  - Multidetector CT (MDCT) angiography is an imaging technique that can provide high
      resolution and high-contrast images; however, published reports of MDCT
      angiography in the evaluation of spinal vascular malformations are limited. We
      present 2 cases in which MDCT angiography led to diagnosis of a type I (spinal
      dural arteriovenous fistula) in one and type IVA (perimedullary spinal cord
      simple arteriovenous fistula fed by a single arterial feeder) spinal vascular
      malformation, both confirmed by conventional angiography. MDCT angiography can
      localize the feeding vessel and the fistula, thus greatly reducing the amount of
      time required for conventional angiography.

PMID- 16611771
TI  - Cystic extramedullary ependymoma.
AB  - Intradural extramedullary location of ependymoma is rare. To the best of our
      knowledge, only 9 cases have been described in the literature. We report a case
      of a histologically confirmed ependymoma (WHO grade II) presented in the MR
      imaging as a cystic, nonenhancing thoracic intradural extramedullary lesion
      compressing the spinal cord. The cystic appearance mimicking an arachnoid cyst at
      diagnosis and the leptomeningeal dissemination developed later were peculiarities
      that have never been previously described in relation to these rare tumors.

PMID- 16611772
TI  - Intracranial time-resolved contrast-enhanced MR angiography at 3T.
AB  - BACKGROUND AND PURPOSE: A method is presented for high-temporal-resolution MR
      angiography (MRA) using a combination of undersampling strategies and a high
      field (3T) scanner. Currently, the evaluation of cerebrovascular disorders
      involving arteriovenous shunting or retrograde flow is accomplished with
      conventional radiographic digital subtraction angiography, because of its high
      spatial and temporal resolutions. Multiphase MRA could potentially provide the
      same diagnostic information noninvasively, though this is technically challenging
      because of the inherent trade-off between signal intensity-to-noise ratio (S/N),
      spatial resolution, and temporal resolution in MR imaging. METHODS: Numerical
      simulations addressed the choice of imaging parameters at 3T to maximize S/N and
      the data acquisition rate while staying within specific absorption rate limits.
      The increase in S/N at 3T was verified in vivo. An imaging protocol was developed
      with S/N, spatial resolution, and temporal resolution suitable for intracranial
      angiography. Partial Fourier imaging, parallel imaging, and the time-resolved
      echo-shared acquisition technique (TREAT) were all used to achieve sufficient
      undersampling. RESULTS: In 40 volunteers and 10 patients exhibiting arteriovenous
      malformations or fistulas, intracranial time-resolved contrast-enhanced MRA with
      high acceleration at high field produced diagnostic-quality images suitable for
      assessment of pathologies involving arteriovenous shunting or retrograde flow.
      The technique provided spatial resolution of 1.1 x 1.1 x 2.5 mm and temporal
      resolution of 2.5 seconds/frame. The combination of several acceleration methods,
      each with modest acceleration, can provide a high overall acceleration without
      the artifacts of any one technique becoming too pronounced. CONCLUSION: By taking
      advantage of the increased S/N provided by 3T magnets over conventional 1.5T
      magnets and converting this additional S/N into higher temporal resolution
      through acceleration strategies, intracranial time-resolved MRA becomes feasible.

PMID- 16611773
TI  - Combinations of the presence or absence of cerebral microbleeds and advanced
      white matter hyperintensity as predictors of subsequent stroke types.
AB  - BACKGROUND AND PURPOSE: Previous studies have shown microbleeds to be a risk
      factor for intracerebral hemorrhage and white matter hyperintensity (WMH) to be a
      risk factor for ischemic stroke. This study was performed to determine whether
      combinations of the presence or absence of microbleeds and advanced WMH are risk
      factors for subsequent recurrent stroke types. METHODS: In 266 patients with
      stroke, microbleeds on T2*-weighted MR images were counted, and WMH on T2
      weighted images was graded. Patients were divided into 4 groups by the
      combinations of the presence or absence of microbleeds and advanced WMH and were
      followed up for stroke recurrence. RESULTS: During a mean follow-up period of
      564.8 +/- 220.5 days, 26 patients developed recurrent strokes, including 10
      intracerebral hemorrhages and 16 ischemic strokes. Patients with microbleeds
      without advanced WMH (n = 42) developed only intracerebral hemorrhages (n = 8),
      and the recurrence rate of intracerebral hemorrhage in those patients estimated
      by the Kaplan-Meier method was the highest in the 4 groups (14.3% in 1 year and
      21.2% in 2 years). In contrast, patients with advanced WMH without microbleeds (n
      = 39) developed only ischemic strokes (n = 6), and the estimated recurrent rate
      of ischemic stroke in those patients was the highest in the 4 groups (10.5% in 1
      year and 17.4% in 2 years). Cox proportional hazards regression analysis revealed
      that microbleeds were associated with intracerebral hemorrhage (hazard ratio
      [HR], 85.626; 95% confidence interval [CI], 6.344-1155.649) and that advanced WMH
      was negatively associated with intracerebral hemorrhage (HR, 0.016; 95% CI, 0.001
      0.258). Advanced WMH was associated with ischemic stroke (HR, 10.659; 95% CI,
      2.601-43.678). CONCLUSION: It appears that patients at high risk of subsequent
      intracerebral hemorrhage or ischemic stroke can be identified by combinations of
      the presence or absence of microbleeds and advanced WMH.

PMID- 16611774
TI  - Widening spectrum of a reversible splenial lesion with transiently reduced
      diffusion.
AB  - Four patients with encephalitis/encephalopathy and parenchymal lesions
      accompanying reversible splenial lesions were retrospectively evaluated. In 3
      patients, reversible lesions with transiently reduced diffusion were seen in the
      splenium and symmetrically in the peripheral frontoparietal white matter,
      clinical signs and symptoms were mild, and recovery was complete. These and
      previous observations suggest a less severe course and outcome for patients with
      reversible lesions isolated to the splenium or to the splenium and peripheral
      frontoparietal white matter.

PMID- 16611775
TI  - Ellipsoid approximation versus 3D rotational angiography in the volumetric
      assessment of intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to compare the volumetric
      results of intracranial aneurysms obtained by calculation of the volume of an
      ellipsoid with those obtained with 3D rotational angiography (3D-RA). METHODS:
      First, the precision of 3D-RA in the assessment of volumetric measurement of
      intracranial aneurysm had to be established. The 3D-RA gave an overestimation of
      4% to 5.5% of the actual volume of a spherical object. Then, 484 consecutive
      human intracranial aneurysms were studied with 3D-RA, allowing the determination
      of their volume. In the meantime, aneurysm dimensions (height and width) were
      measured on the 3D pictures generated by the 3D-RA. The aneurysm volumes were
      obtained by considering the aneurysm shape to be ellipsoidal, according to the
      formula: (formula in text). RESULTS: The calculated aneurysm volume (V(calc))
      overestimated by 15 +/- 38% the volume given by 3D-RA. Taking into account a 10%
      margin of error, 227 (47%) aneurysms were overestimated by 44 +/- 34%, whereas
      113 (23%) aneurysms were underestimated by 25 +/- 12%. Only 144 (30%) aneurysms
      had calculated and 3D-RA results within the limits of 10% of discrepancy.
      Concordance was good for pericallosal and basilar tip aneurysms (mean
      overestimation of 6 +/- 22% and 8 +/- 27%, respectively). Conversely, there was a
      high discrepancy between calculated and 3D-RA results for posterior communicating
      artery aneurysms (mean overestimation of 22 +/- 44%). CONCLUSION: The calculation
      of the volume based on aneurysm dimensions is relatively accurate for
      pericallosal and basilar tip aneurysms, probably owing to their spherical or
      elliptic shape. Conversely, this formula is not adequate for irregularly shaped
      lesions, such as posterior communicating aneurysms.

PMID- 16611776
TI  - Artifact simulating subarachnoid and intraventricular hemorrhage on single-shot,
      fast spin-echo fluid-attenuated inversion recovery images caused by head
      movement: A trap for the unwary.
AB  - BACKGROUND AND PURPOSE: Single-shot, fast spin-echo, fluid attenuated inversion
      recovery (SS-FSE-FLAIR) images are frequently used to detect disease in the brain
      and subarachnoid space in confused or uncooperative patients who may move during
      the examination. In some of these patients, high signal intensity areas are seen
      on good-quality images in the subarachnoid space and ventricular system in
      locations not associated with high CSF flow. These artifacts may simulate
      hemorrhage or leptomeningeal disease. The purpose of this article was to
      determine the cause of these artifacts, describe ways to recognize them, and find
      methods to reduce or eliminate them. METHODS: Healthy volunteers were studied on
      6 occasions with conventional multisection FSE-FLAIR images and SS-FSE-FLAIR
      images while at rest and while nodding and rotating their heads at different
      speeds. In addition, SS-FSE-FLAIR images with different section widths of the
      initial inverting pulse and a non-section-selective initial inversion pulse were
      performed with the subjects moving their heads in the same way. The scans of 30
      successive patients with acute neurologic syndromes who had been studied with SS
      FSE-FLAIR sequences were reviewed for evidence of high signal intensity in the
      CSF in regions not associated with high CSF flow. RESULTS: Each of the volunteers
      showed areas of increased signal intensity in CSF at sites apart from those
      associated with rapid pulsatile CSF flow on SS-FSE-FLAIR images acquired during
      head motion. The images were otherwise virtually free of motion artifact. The use
      of a wider initial inversion pulse section and a non-section-selected initial
      inversion pulse reduced the extent of these artifacts. Nineteen of the 30
      patients showed areas of high signal intensity in the CSF in regions not
      associated with highly pulsatile CSF flow. Six of these patients had negative
      lumbar punctures for blood and xanthochromia and normal CSF protein levels.
      CONCLUSION: High signal intensity artifacts may be seen in CSF as a result of
      head movement on otherwise artifact-free images when imaging uncooperative
      patients with SS-FSE-FLAIR sequences. These artifacts have a different mechanism
      and distribution from those caused by CSF pulsation and may simulate subarachnoid
      and intraventricular hemorrhage. Artifact recognition is aided by signs of
      patient motion during the examination. The artifacts can be reduced by use of
      increased section width and non-section-selective initial inversion pulses.
      Recognition of these artifacts is important, because the circumstances in which
      the SS-FSE-FLAIR sequence is used and the particular properties of the sequence
      may conspire to produce a trap for the unwary.

PMID- 16611777
TI  - Feathering: Vertebral artery pseudostenosis with elliptical centric contrast
      enhanced MR angiography.
AB  - Elliptical centric contrast-enhanced MR angiography of the cervical vasculature
      is a well-established technique that in many practices has replaced conventional
      angiography for several clinical indications, including atherosclerotic disease
      and dissections. Occasionally blurring or loss of signal intensity occurs in the
      vertebral arteries, especially in young patients with rapid circulation times.
      This ringing artifact, which we termed "feathering," results from rapidly
      changing signal intensity in small vascular structures during the sampling of the
      center of k-space.

PMID- 16611778
TI  - Do cerebral blood volume and contrast transfer coefficient predict prognosis in
      human glioma?
AB  - INTRODUCTION: Noninvasive measurements of cerebral blood volume (CBV) and
      contrast transfer coefficient (K(trans)) have potential benefits in the diagnosis
      and therapeutic management of adult glioma. This study examines the relationship
      between CBV, K(trans), and overall survival. METHODS AND MATERIALS: Twenty-seven
      adult patients with glioma underwent T1-weighted dynamic contrast-enhanced MR
      imaging, and parametric maps of CBV and K(trans) were calculated. The
      relationship of histologic grade, CBV, K(trans), age, sex, surgical resection,
      and use of adjuvant therapy to survival were analyzed by using the logrank method
      and Cox regression analysis. The Kaplan-Meier method for displaying survival
      curves was used. The relationship of factors such as comorbidity, elevated
      intracranial pressure, size of nonenhancing tumor, and peritumoral edema were not
      considered. RESULTS: Both CBV (P < .01) and K(trans) (P < .01) show a significant
      relationship to histologic grade. CBV (P = .004), K(trans) (P = .008), and
      histologic grade (P < .001) all demonstrate a significant association with
      patient survival when analyzed individually. Cox regression analysis identified
      only histologic grade (P < .01) and K(trans) (P < .05) as independent significant
      prognostic indicators. Examination of survival data from high-grade (III and IV)
      tumors demonstrated a linear relationship between K(trans) and patient survival
      (P < .01). CONCLUSION: This study suggests a direct relationship between K(trans)
      and length of survival in high-grade gliomas, which could be of clinical
      importance. CBV relates directly to histologic grade but provides no independent
      prognostic information over and above that provided by grade. Further large
      prospective studies should be planned to test whether this observation holds
      true.

PMID- 16611779
TI  - Relative cerebral blood volume maps corrected for contrast agent extravasation
      significantly correlate with glioma tumor grade, whereas uncorrected maps do not.
AB  - BACKGROUND AND PURPOSE: Relative cerebral blood volume (rCBV) estimates for high
      grade gliomas computed with dynamic susceptibility contrast MR imaging are
      artificially lowered by contrast extravasation through a disrupted blood-brain
      barrier. We hypothesized that rCBV corrected for agent leakage would correlate
      significantly with histopathologic tumor grade, whereas uncorrected rCBV would
      not. METHODS: We performed dynamic T2*-weighted perfusion MR imaging on 43
      patients with a cerebral glioma after prebolus gadolinium diethylene triamine
      penta-acetic acid administration to diminish competing extravasation-induced T1
      effects. The rCBV was computed from non-necrotic enhancing tumor regions by
      integrating the relaxivity-time data, with and without contrast extravasation
      correction by using a linear fitting algorithm, and was normalized to
      contralateral brain. We determined the statistical correlation between corrected
      and uncorrected normalized rCBV and histopathologic tumor grade with the Spearman
      rank correlation test. RESULTS: Eleven, 9, and 23 patients had WHO grades II,
      III, and IV glioma, respectively. Mean uncorrected normalized rCBVs were 1.53,
      2.51, and 2.14 (grade II, III, and IV). Corrected normalized rCBVs were 1.52,
      2.84, and 3.96. Mean absolute discrepancies between uncorrected and corrected
      rCBVs were 2% (0%-15%), 16% (0%-106%), and 74% (0%-411%). The correlation between
      corrected rCBV and tumor grade was significant (0.60; P < .0001), whereas it was
      not for uncorrected rCBV (0.15; P = .35). CONCLUSION: For gliomas, rCBV
      estimation that correlates significantly with WHO tumor grade necessitates
      contrast extravasation correction. Without correction, artificially lowered rCBV
      may be construed erroneously to reflect lower tumor grade.

PMID- 16611780
TI  - Voxel-based analysis of quantitative T1 maps demonstrates that multiple sclerosis
      acts throughout the normal-appearing white matter.
AB  - BACKGROUND AND PURPOSE: Disease activity in normal-appearing white matter (NAWM)
      in multiple sclerosis (MS) has been demonstrated in vivo with T1 relaxation time
      measurements. We aimed to investigate the spatial distribution of T1 increases in
      MS NAWM without a priori selection of specific regions. METHODS: Whole-brain
      quantitative T1 maps were measured in 67 patients with one of the 3 main clinical
      types of MS (13 primary progressive [PP], 36 relapsing-remitting [RR], and 18
      secondary progressive [SP]) and in 23 healthy control subjects. After
      registration to standard space and segmentation of NAWM, the maps were analyzed
      by using voxel-based analyses with a cluster-based corrected P threshold of .05.
      RESULTS: Group mean T1 relaxation times throughout NAWM increased when going from
      control subjects to PP to RR to SP MS. In the RR and SP MS groups, the T1
      increases compared with control subjects were significant throughout the NAWM,
      without apparent preference for specific brain regions. In RR MS, 16% of NAWM
      voxels displayed a significant increase in T1 compared with control subjects, and
      in SP, this fraction was 49%. The comparison between RR MS and the subsequent
      phase SP MS revealed that, in these patients, disease progression occurs
      throughout the NAWM. In patients with PP MS, the spatial extent of significant T1
      increases is limited. There were no correlations with clinical disability scales
      or brain volume in a substantial fraction of voxels. CONCLUSION: This study
      demonstrates that in patients with RR MS and SP MS, NAWM disease processes have
      no regional preferences but can occur throughout the brain.

PMID- 16611781
TI  - Measuring longitudinal white matter changes: comparison of a visual rating scale
      with a volumetric measurement.
AB  - BACKGROUND AND PURPOSE: Detection of longitudinal changes in white matter
      hyperintensities (WMH) by using visual rating scales is problematic. We compared
      a widely used visual rating scale with a volumetric method to study longitudinal
      white matter changes. METHODS: WMH were assessed with the visual Scheltens scale
      and a volumetric method in 100 elderly subjects aged 70-81 years for whom
      repetitive MR images were available with an interval of 33 (SD, 1.4) months.
      Reliability was determined by intraclass correlation coefficients. To examine the
      sensitivity of both the visual and volumetric method, we calculated Spearman rank
      correlations of WMH ratings and volume measurements with age. RESULTS:
      Reliability of the visual rating scale was good, whereas reliability of the
      volumetric measurement was excellent. For baseline measurements of WMH, we found
      weaker associations between WMH and age when assessed with the visual scale (r =
      0.20, P = .045) than with the volumetric method (r = 0.31, P = .002).
      Longitudinal evaluation of WMH assessments showed regression in 26% of the
      subjects when analyzed with the visual rating scale against 12% of the subjects
      when using volumetric measurements. Compared with the visual rating, the
      correlation between progression in WMH and age was twice as high when using the
      volumetric measurement (r = 0.19, P = .062 and r = 0.39, P < .001, respectively).
      CONCLUSION: Volumetric measurements of WMH offer a more reliable, sensitive, and
      objective alternative to visual rating scales in studying longitudinal white
      matter changes.

PMID- 16611782
TI  - Corpus callosum diffusion anisotropy correlates with neuropsychological outcomes
      in twins disconcordant for traumatic brain injury.
AB  - Conventional and diffusion tensor MR imaging studies in twins sustaining severe
      pediatric traumatic brain injury identified reduction in fractional anisotropy
      (FA) in all regions of the corpus callosum, particularly the posterior body,
      rostral body, and genu, relative to healthy cotwins. FA from the rostrum, genu,
      anterior body, posterior body, and isthmus were correlated with measures of
      reading speed and comprehension; verbal working memory and math fact retrieval
      scores were correlated only with the rostral body FA.

PMID- 16611783
TI  - Spontaneous resolution of posttraumatic middle meningeal artery pseudoaneurysm.
AB  - We present a case of traumatic pseudoaneurysm of the middle meningeal artery
      (demonstrated on CT angiogram) associated with epidural hematoma that
      spontaneously resolved without treatment. Follow-up CT angiogram and conventional
      angiogram done 2 weeks later demonstrated complete resolution of the
      pseudoaneurysm. The literature suggests that these lesions require urgent
      treatment because they have a high mortality rate. We highlight the lack of
      proper data regarding the natural history of this disease and therefore lack of
      treatment guidelines.

PMID- 16611784
TI  - Diffuse CNS vasculopathy with chronic Epstein-Barr virus infection in X-linked
      lymphoproliferative disease.
AB  - We report a patient with X-linked lymphoproliferative disease (XLP) who developed
      multiple central nervous system (CNS) manifestations of Epstein-Barr virus
      infection. XLP, or Duncan syndrome, is a rare inherited disorder characterized by
      the inability to clear Epstein-Barr virus infection. In addition to Epstein-Barr
      virus encephalitis, CNS lymphoproliferative disease, and lymphoma, this patient
      also developed MR angiographic evidence of diffuse fusiform aneurysmal dilation
      of intracranial vessels.

PMID- 16611785
TI  - MR imaging of human herpesvirus-6-associated encephalitis in 4 patients with
      anterograde amnesia after allogeneic hematopoietic stem-cell transplantation.
AB  - MR imaging is typically obtained during the work-up of patients who have
      undergone allogeneic hematopoietic stem-cell transplant who present with
      unexplained change in mental status, amnesia, or seizures. Although the
      differential diagnosis is broad in this setting, the presence of T2 prolongation
      limited to the medial aspect of one or both temporal lobes with or without
      associated reduced water diffusion may help limit the possible diagnoses. A
      frequent etiology seen in this context is human herpesvirus-6 (HHV6) infection.
      We report the evolution of MR imaging findings and clinical course in 4 patients
      with limbic encephalitis probably related to HHV6.

PMID- 16611786
TI  - MR imaging assessment of brain and cervical cord damage in patients with
      neuroborreliosis.
AB  - BACKGROUND AND PURPOSE: Neuroborreliosis is frequently indistinguishable from
      multiple sclerosis (MS) on both clinical and radiologic grounds. By using MR
      imaging, we assessed "occult" brain white matter (WM), brain gray matter (GM),
      and cervical cord damage in patients with neuroborreliosis in an attempt to
      achieve a more accurate picture of tissue damage in these patients, which might
      contribute to the diagnostic work-up. METHODS: We studied 20 patients with
      neuroborreliosis and 11 sex- and age-matched control subjects. In all subjects,
      we acquired dual echo, T1-weighted, diffusion tensor (DT) and magnetization
      transfer (MT) MR imaging scans of the brain and fast short-tau inversion recovery
      and MT MR imaging scans of the cervical cord. T2-visible lesion load was measured
      by using a local thresholding segmentation technique. Mean diffusivity and
      fractional anisotropy histograms of the brain and cervical cord MT ratio
      histograms were produced. Normalized brain volumes (NBV) were measured by using
      SIENAx. RESULTS: Brain T2-visible lesions were detected in 12 patients, whereas
      no occult damage in the normal-appearing WM and GM was disclosed by using MT and
      DT MR imaging. No macroscopic lesions were found in the cervical cord, which was
      also spared by occult pathology. NBV did not differ between patients with
      neuroborreliosis and control subjects. CONCLUSION: This study shows that,
      contrary to what happens in MS, occult brain tissue damage and cervical cord
      pathology are not frequent findings in patients with neuroborreliosis. These
      observations might be useful in the diagnostic work-up of patients with
      neuroborreliosis and T2 brain lesions undistinguishable from those of MS.

PMID- 16611787
TI  - Pitfalls in lactate measurements at 3T.
AB  - In clinical MR spectroscopy at higher field strengths, lactate may show reduced
      or absent signal intensity at an echo time of 144 ms. Although this false
      negative result may be predicted from theory, experimental verification and
      clinical impact have not been fully established. Using scanners from 3 major
      vendors, spectra from phantoms and patients demonstrate the lactate signal loss
      and potential error in interpretation. Strategies are discussed to overcome, or
      at least alleviate, this problem.

PMID- 16611788
TI  - Pre- and posttreatment MR imaging findings in lead encephalopathy.
AB  - A 41-year-old man suspected of having lead poisoning was evaluated with MR
      imaging before and after British antilewisite therapy. The MR imaging findings
      showed bilateral symmetric involvement of the occipital lobe, affecting
      predominantly the gray-white matter junction and the subcortical white matter. A
      right cerebellar lesion was noted, with focal hyperintensities involving the gray
      white matter. Similar lesions were seen in the temporal, parietal, and frontal
      regions. These lesions resolved after chelation therapy.

PMID- 16611789
TI  - MR characteristics and neuropathology in adult-onset autosomal dominant
      leukodystrophy with autonomic symptoms.
AB  - BACKGROUND AND PURPOSE: Three families with adult-onset autosomal dominant
      leukodystrophy (ADLD) presenting autonomic dysfunction as the first symptom are
      reported. We describe detailed MR appearances of the brain in 2 new families and
      neuropathology in 2 patients and compare the findings with those in other adult
      onset leukodystrophies. METHODS: Twenty subjects (12 women and 8 men; age range,
      29-70 years) from 2 unrelated families with ADLD were examined with MR. Six
      subjects were asymptomatic. Fourteen had autonomic dysfunction. Eleven of them
      also had pyramidal signs and ataxia. The brains of 2 autopsied patients were
      examined histopathologically. RESULTS: Two subjects manifested no neurologic
      symptoms, signs, or MR pathology. Eighteen subjects displayed radiologic
      abnormalities ranging from subtle T2 high-signal-intensity changes in the upper
      corticospinal tract to extensive confluent white matter changes, predominantly in
      a frontoparietal distribution, along the corticospinal tracts down to the medulla
      oblongata and in the upper and middle cerebellar peduncles. Periventricular white
      matter was spared or less affected than the adjacent white matter. Histopathology
      revealed marked loss of cerebral and cerebellar myelin without signs of
      inflammation. Oligodendrocytes were relatively spared, the number of axons not
      markedly decreased, and reactive gliosis was modest. The number of Purkinje cells
      in the cerebellum was reduced. CONCLUSIONS: Two families with adult-onset ADLD
      with the disease entity originally reported by Eldridge et al. (N Engl J Med
      1984;311:948-53) were described. We propose naming the disease "adult-onset ADLD
      with autonomic symptoms." The characteristic radiologic findings, combined with
      the clinical symptoms and mode of inheritance, enable the diagnosis.

PMID- 16611790
TI  - Hippocampal cerebrospinal fluid spaces on MR imaging: Relationship to aging and
      Alzheimer disease.
AB  - BACKGROUND AND PURPOSE: Perihippocampal fissures (PHFs) and hippocampal sulcus
      residual cavities (HSCs) are common findings in the MR imaging examination of the
      hippocampus in aging and Alzheimer disease (AD); however, little is known about
      how to distinguish them or their relative clinical relevance. We hypothesized
      that prominence of the HSC, unlike PHF, is not significantly influenced by the
      hippocampal atrophy related to aging or AD. METHODS: We studied and evaluated
      these hippocampal CSF spaces on MR imaging scans from 130 normal control (NC)
      subjects (20-90 years of age) and 27 AD patients. RESULTS: HSC is poorly
      correlated with age and is not related to the magnitude of hippocampal atrophy.
      There is no significant difference of HSCs between AD and age-matched NCs, but in
      the extremely high HSCs group (top 20%), 91% of cases are NC. PHFs, on the other
      hand, are strongly correlated with age and are valuable in the diagnosis of AD.
      Location and communication with ambient cistern is the key to distinguish HSC
      from PHF. CONCLUSION: Identifying hippocampal atrophy (enlarged PHF) may be
      particularly challenging in the presence of HSC. Distinguishing among the CSF
      spaces in hippocampus may help in the radiologic evaluation of hippocampal
      atrophy. Patients with extremely high HSCs (>8.4) can be excluded from AD risk
      with 93% specificity.

PMID- 16611791
TI  - Xanthoma disseminatum of the central nervous system and cranium.
AB  - Xanthoma disseminatum is a rare normolipemic histiocytic disorder of non
      Langerhans cell origin. It is a chronic systemic disease with a benign course,
      characterized by disseminated, yellow-orange-colored papules on the face,
      flexures, and mucosal membranes. We report 3 patients with xanthoma disseminatum,
      who presented primarily with central nervous system disease and a multitude of
      imaging findings throughout the craniospinal axis.

PMID- 16611793
TI  - CT and MR imaging findings in sinonasal schwannoma.
AB  - We report a rare case of schwannoma of the sinonasal cavity, presenting with
      epistaxis and anosmia.

PMID- 16611792
TI  - Vital signs investigation in subjects undergoing MR imaging at 8T.
AB  - PURPOSE: This study investigates physiologic vital signs in subjects, with and
      without cerebral pathologies, undergoing ultra-high-field (UHF) 8T MR imaging.
      METHODS AND SUBJECTS: Eighteen normal subjects and 74 subjects with cerebral
      pathology consented for 8T UHF MR imaging. T2*-weighted gradient-echo and T2
      weighted rapid acquisition relaxation excitement sequences were used. Physiologic
      vital signs measured included systolic blood pressure, diastolic blood pressure,
      mean arterial pressure, electrocardiogram, heart rate (HR), respiratory rate
      (RR), and pulse oxygen saturation rate. They were collected before, during, and
      after imaging. Mean vital sign values at different stages were calculated and
      compared. Subjects were interviewed after imaging. RESULTS: No adverse vital sign
      change was detected. Statistically significant changes after imaging included a
      HR decrease from 65.2 beats per minute (bpm) to 60.3 bpm (P = .001, paired
      Student t test) in the normal group and a RR increase from 14.5 respirations per
      minute (rpm) to 15.1 rpm (P = .001, paired Student t test) in the patient group.
      Transient vertigo sensation was reported by 27% of normal subjects and 11% of
      subjects with cerebral pathologies. One normal subject and one subject with
      cerebral pathology reported an episode of nausea and vomiting. CONCLUSION: The
      current neurologic human MR imaging procedure at 8T UHF has no serious adverse
      effects on major physiologic vital signs in either normal subjects or patients.
      Transient vertigo, nausea, and vomiting were identified as potential risks.

PMID- 16611795
TI  - Extramedullary hematopoiesis involving the bilateral lacrimal fossae.
AB  - Extramedullary hematopoiesis is a complication of a number of myeloproliferative
      disorders. MR imaging of the orbits was performed in a patient with bilateral
      orbital swelling with known myeloproliferative disorder and myelofibrosis. The
      study revealed symmetric, bilateral enhancing masses in the lacrimal fossae
      extending into the nasolacrimal ducts. Biopsy demonstrated sclerotic
      extramedullary hematopoietic tumor.

PMID- 16611794
TI  - Kaposiform hemangioendothelioma arising from the internal auditory canal.
AB  - Kaposiform hemangioendothelioma is a rare vascular tumor and locally aggressive
      endothelial-derived spindle cell neoplasm, which occurs almost exclusively in
      infants and adolescents. Radiologically, hemangioendothelioma, including
      Kaposiform hemangioendothelioma, is seen as a highly vascularized well-enhancing
      tumor, but no characteristic findings differentiate Kaposiform
      hemangioendothelioma from other soft-tissue tumors, particularly when the tumor
      is too small to have any locally aggressive features or identifiable large
      vessels. We present a case of Kaposiform hemangioendothelioma in the internal
      auditory canal that had no differential features on initial MR images and rapidly
      grew into a huge mass in a few months.

PMID- 16611796
TI  - Herniation of the buccal fat pad into the maxillary antrum: CT findings in three
      cases.
AB  - We report the first 3 cases in which CT disclosed herniation of the body of the
      buccal fat pad into the maxillary antrum. Only 20 cases of traumatic herniation
      of the buccal fat pad have been described in the literature. In all except one
      instance, the buccal fat pad herniated into the oral cavity. The only previous
      report of herniation of the buccal fat pad into the maxillary antrum is in an
      article published before modern cross-sectional imaging, and the diagnosis was
      not made preoperatively in that case.

PMID- 16611797
TI  - Intrasubject reproducibility of functional MR imaging activation in language
      tasks.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to examine the
      reproducibility of functional MR imaging (fMRI) activation (volume and
      laterality) within both inferior frontal and temporoparietal regions of interest
      for both receptive and expressive language tasks. METHODS: Ten healthy volunteers
      participated in fMRI experiments for 6 language tasks: verb generation,
      confrontation naming, semantic decision making, visual sentence comprehension,
      auditory sentence comprehension, and story listening. Each subject was scanned
      during 2 separate sessions separated by a minimum of 4 weeks. Laterality of
      activation was defined by laterality indices (LIs), which were calculated by 2
      methods: one method based on the measured volume of activation and the other
      method based on the F statistic of the activation. Reproducibility was calculated
      by using concurrence ratios for the volume of activation (R(overlap), R(volume))
      and test-retest correlation for LIs. RESULTS: All tasks generated reproducible
      LIs within at least one of the regions of interest, but verb generation produced
      the highest test-retest correlations (r = 0.99) within both regions of interest.
      Verb generation was associated with the highest average concurrence ratios within
      the inferior frontal region of interest (R(overlap) = 45.2; R(volume) = 70.9). In
      general, the concurrence ratios were lower within the temporoparietal region of
      interest compared with the inferior frontal region of interest. LIs calculated
      with F statistics were more reproducible than the LIs calculated by activation
      volume. CONCLUSION: fMRI is able to provide reproducible LIs in both inferior
      frontal and temporoparietal regions for assessing hemispheric dominance in
      language processing. The volume of activation, especially within the
      temporoparietal regions, is less reproducible than the laterality of activation,
      so the former should be used with caution.

PMID- 16611801
TI  - The effect of temperature differences on the distribution of an airborne
      contaminant in an experimental room.
AB  - Estimating exposure to contaminants emitted into workroom air is essential for
      worker protection. Although contaminant concentrations are often not spatially
      uniform within workrooms, many methods for estimating exposure do not adequately
      account for this variability. Here the impact of temperature differences within a
      room on spatial contaminant distribution was studied. Tracer gas (99.5%
      propylene) concentrations were monitored automatically at 144 sampling points
      with a photoionization detector. One wall was chosen to represent a building's
      external wall and was heated or cooled to simulate summer or winter conditions.
      Experiments were preformed at two flow rates (5.5 and 3.3 m(3) min(-1)) and six
      thermal conditions (isothermal, three summer conditions and two winter
      conditions). For 5.5 m(3) min(-1) and all thermal conditions, the coefficient of
      variation (CV) ranged from 0.34 to 0.45 and the normalized average concentrations
      were similar. For 3.3 m(3) min(-1), winter conditions produced greater spatial
      variability of concentration (CV = 0.72 and 1.10) than isothermal or summer
      conditions (CV range = 0.29-0.34). Tests simulating winter conditions suggest
      that the resulting stable temperature structure inhibited the dilution of the
      tracer and enhanced its segregation in the lower portion of the room, especially
      for the lower flow rate (3.3 m(3) min(-1)). Therefore, not explicitly addressing
      thermal effect in exposure modeling may impact the estimated accuracy and
      precision when used for rooms that are non-isothermal and not well mixed. These
      findings also have implications for air monitoring. Dispersion patterns for
      different thermal conditions were found to be substantially different, even when
      the mean concentrations were nearly the same. Thus, monitoring data from a single
      season should not be taken as representative of the entire year, when summer and
      winter conditions create temperature gradients in a room.

PMID- 16611802
TI  - The time course of shifting visual attention.

PMID- 16611803
TI  - Policing the police: astrocytes modulate microglial activation.

PMID- 16611804
TI  - Spike-timing codes enhance the representation of multiple simultaneous sound
      localization cues in the inferior colliculus.
AB  - To preserve multiple streams of independent information that converge onto a
      neuron, the information must be re-represented more efficiently in the neural
      response. Here we analyze the increase in the representational capacity of spike
      timing over rate codes using sound localization cues as an example. The inferior
      colliculus receives convergent input from multiple auditory brainstem nuclei,
      including sound localization information such as interaural level differences
      (ILDs), interaural timing differences (ITDs), and spectral cues. Virtual space
      techniques were used to create stimulus sets varying in two sound-localization
      parameters each. Information about the cues was quantified using a spike distance
      metric that allows one to separate contributions to the information arising from
      spike rate and spike timing. Spike timing enhances the representation of spectral
      and ILD cues at timescales averaging 12 ms. ITD information, however, is carried
      by a rate code. Comparing responses to frozen and random noise shows that the
      temporal information is mainly attributable to phase locking to temporal stimulus
      features, with an additional first-spike latency component. With rate-based
      codes, there is significant confounding of information about two cues presented
      simultaneously, meaning that the cues cannot be decoded independently. Spike
      timing-based codes reduce this confounded information. Furthermore, the relative
      representation of the cues often changes as a function of the time resolution of
      the code, implying that information about multiple cues can be multiplexed onto
      individual spike trains.

PMID- 16611805
TI  - Brain-derived neurotrophic factor is critically involved in thermal-experience
      dependent developmental plasticity.
AB  - All species exhibit critical period for sensory development, yet very little is
      known about the molecules involved in the changes in the network wiring that
      underlies this process. Here the role of brain-derived neurotrophic factor (BDNF)
      in the critical period of thermal control establishment in chicks was
      investigated. Neuroanatomically, the body temperature is balanced by the preoptic
      anterior hypothalamus (PO/AH) and controlled by thermosensitive neurons. Exposure
      to hot or cold conditions during the critical period of temperature control
      development causes a plastic change in the ratio between heat- and cold-sensitive
      cells and can modulate temperature tolerance. It was found that expression of
      BDNF mRNA but not of NGF or neurotrophin-3 was induced in the PO/AH of 3-d-old
      chicks during both heat and cold exposure. The peak of BDNF induction in both
      heat and cold exposure occurred after 6 h, with, respectively, threefold and
      sevenfold increases in its mRNA expression. To prove the concept that BDNF
      activation is a critical step in thermal-experience-dependent plasticity, BDNF
      was "knocked down" using antisense. It was found that, when BDNF in the PO/AH was
      inhibited by 80% during the third postnatal day, thermal establishment was
      impaired, and, after 1 week, the chicks' body temperature was reduced by 0.5
      degrees C. Furthermore, later in life, their reaction to thermal challenge was
      altered, and they exhibited a pronounced reduction in their ability to maintain
      their body temperature and body weight under harsh conditions. Together, these
      results prove that BDNF is critically involved in thermal-experience-dependent
      development.

PMID- 16611806
TI  - Random wiring in the midget pathway of primate retina.
AB  - The present study addresses the questions of how topographically organized
      neuronal populations are connected, and whether there is anatomical evidence for
      color-selective wiring in retinal pathways for red-green color vision. The
      connectivity of OFF midget bipolar and OFF midget ganglion cells was studied in
      the peripheral retina of dichromatic ("red-green color blind") and trichromatic
      ("color normal") marmosets (Callithrix jacchus). Midget bipolar cells were
      identified immunohistochemically. Midget ganglion cells were retrogradely labeled
      from the lateral geniculate nucleus and photofilled. Comparable results were
      obtained from all retinas studied. Between 3 and 16 bipolar terminals converge
      onto each ganglion cell. Nearly all bipolar terminals investigated show regions
      of colocalization (areas of presumed synaptic contacts) with ganglion cell
      dendrites. This contact area makes up approximately 14% of the axon surface area
      for a typical midget bipolar cell. The output from individual midget bipolar
      axons is often shared between midget ganglion cells so that, on average, <70% of
      the axon terminal area of a midget bipolar cell shows overlap with the dendritic
      field of a given midget ganglion cell. We conclude that there is no morphological
      evidence of red-green color selectivity in the connections between midget bipolar
      and midget ganglion cell mosaics. Furthermore, the results suggest that
      convergence is based on local interactions between axons and dendrites rather
      than cell-by-cell recognition between members of each mosaic.

PMID- 16611807
TI  - Additive effects of genetic variation in dopamine regulating genes on working
      memory cortical activity in human brain.
AB  - Functional polymorphisms in the catechol-O-methyltransferase (COMT) and the
      dopamine transporter (DAT) genes modulate dopamine inactivation, which is crucial
      for determining neuronal signal-to-noise ratios in prefrontal cortex during
      working memory. We show that the COMT Met158 allele and the DAT 3' variable
      number of tandem repeat 10-repeat allele are independently associated in healthy
      humans with more focused neuronal activity (as measured with blood oxygen level
      dependent functional magnetic resonance imaging) in the working memory cortical
      network, including the prefrontal cortex. Moreover, subjects homozygous for the
      COMT Met allele and the DAT 10-repeat allele have the most focused response,
      whereas the COMT Val and the DAT 9-repeat alleles have the least. These results
      demonstrate additive genetic effects of genes regulating dopamine signaling on
      specific neuronal networks subserving working memory.

PMID- 16611808
TI  - Low doses of memantine disrupt memory in adult rats.
AB  - Memantine, a drug recently approved for treatment of Alzheimer's disease, has
      been characterized as a unique NMDA antagonist that confers protection against
      excitotoxic neurodegeneration without the serious side effects that other NMDA
      antagonists are known to cause. In the present study, we determined what dose of
      memantine is required to protect the adult rat brain against an NMDA receptor
      mediated excitotoxic process and then tested that dose and a range of lower doses
      to determine whether the drug in this dose range is associated with significant
      side effects. Consistent with previous research, we found that memantine confers
      a neuroprotective effect beginning at an intraperitoneal dose of 20 mg/kg, a dose
      that we found, contrary to previous reports, produces locomotor disturbances
      severe enough to preclude testing for learning and memory effects. We then
      determined that, at intraperitoneal doses of 10 and 5 mg/kg, memantine disrupts
      both memory and locomotor behaviors. Rats treated with these doses performed at
      control-like levels in learning a hole-board task but were significantly impaired
      in demonstrating what they had learned when tested 24 h later. This impairment of
      memory retention was not state dependent in that it was demonstrable regardless
      of whether the rats were or were not exposed to memantine on the day of retention
      testing. We conclude that, in the adult rat, memantine behaves like other NMDA
      antagonists in that it is neuroprotective only at doses that produce intolerable
      side effects, including memory impairment.

PMID- 16611809
TI  - Aging-dependent alterations in synaptic plasticity and memory in mice that
      overexpress extracellular superoxide dismutase.
AB  - Oxidative damage caused by reactive oxygen species (ROS) has been proposed to be
      critically involved in several pathological manifestations of aging, including
      cognitive dysfunction. ROS, including superoxide, are generally considered as
      neurotoxic molecules whose effects can be alleviated by antioxidant enzymes.
      However, ROS also are known to be necessary components of the signal transduction
      cascades underlying normal synaptic plasticity. Therefore, we reasoned that the
      role that ROS and antioxidant enzymes play in modulating neuronal processes
      varies over the lifespan of an animal. We examined hippocampal long-term
      potentiation (LTP) and memory-related behavioral performance in transgenic mice
      overexpressing extracellular superoxide dismutase (EC-SOD) and their wild-type
      littermates at different ages. We found that aged EC-SOD transgenic mice
      exhibited enhanced hippocampal LTP, better cerebellum-dependent motor learning,
      and better hippocampus-dependent spatial learning compared with their wild-type
      littermates. We also found that EC-SOD overexpression impaired contextual
      learning, but the impairment was decreased in the aged transgenic mice. At the
      molecular level, aged EC-SOD transgenic mice had lower superoxide levels, a
      decrease in protein carbonyl levels, and a decrease in p38 and extracellular
      signal-regulated kinase 2 phosphorylation compared with aged wild-type mice. Our
      findings suggest that elevated levels of superoxide contribute to aging-related
      impairments in hippocampal LTP and memory, and that these impairments can be
      alleviated by overexpression of EC-SOD. We conclude that there is an age
      dependent alteration in the role of superoxide in modulating synaptic plasticity
      and learning and memory.

PMID- 16611810
TI  - Pathological changes in dopaminergic nerve cells of the substantia nigra and
      olfactory bulb in mice transgenic for truncated human alpha-synuclein(1-120):
      implications for Lewy body disorders.
AB  - Dysfunction of the 140 aa protein alpha-synuclein plays a central role in Lewy
      body disorders, including Parkinson's disease, as well as in multiple system
      atrophy. Here, we show that the expression of truncated human alpha-synuclein(1
      120), driven by the rat tyrosine hydroxylase promoter on a mouse alpha-synuclein
      null background, leads to the formation of pathological inclusions in the
      substantia nigra and olfactory bulb and to a reduction in striatal dopamine
      levels. At the behavioral level, the transgenic mice showed a progressive
      reduction in spontaneous locomotion and an increased response to amphetamine.
      These findings suggest that the C-terminal of alpha-synuclein is an important
      regulator of aggregation in vivo and will help to understand the mechanisms
      underlying the pathogenesis of Lewy body disorders and multiple system atrophy.

PMID- 16611811
TI  - Long-term effects of brief acute stress on cellular signaling and hippocampal
      LTP.
AB  - In a previous study, we reported that a brief exposure to swim stress transforms
      an electrically induced, protein synthesis-independent early long-term
      potentiation (early LTP) into a protein synthesis-dependent late LTP
      ["reinforcement of LTP" in the hippocampal dentate gyrus (DG)] (Korz and Frey,
      2003). This transformation depends on activation of mineralocorticoid receptors
      (MRs) by corticosterone, and on intact basolateral amygdala (BLA) function. Here,
      we demonstrate that a brief swim experience results in lasting changes in levels
      of hippocampal cellular signaling molecules that are known to be involved in the
      induction of late LTP. Within the DG, MRs were rapidly upregulated, whereas
      glucocorticoid receptor (GR) levels were elevated with a 3 h delay. Levels of
      phosphorylated mitogen-activated protein kinase 2 (pMAPK2) and p38 MAPK, as well
      as phosphorylated calcium/calmodulin-dependent protein kinase II (pCaMKII) were
      enhanced shortly after swim stress and remained elevated until 24 h, whereas
      levels of phosphorylated cAMP response element-binding protein (pCREB) remained
      unchanged. MR and GR were upregulated with a longer delay within the CA1 region,
      whereas levels of pMAPK2 and p38MAPK were rapidly increased, but the former
      returned to basal levels after 3 h. Levels of pCREB and pCaMKII were maintained
      in an enhanced state after swim stress. DG-LTP reinforcement requires a
      serotonergic but not dopaminergic heterosynaptic receptor activation that
      probably mediates the BLA-dependent modulation of LTP under stress. Thus,
      molecular alterations induced by specific stress resemble late LTP-related
      molecular changes. These changes, in interaction with stress-specific
      heterosynaptic processes, may support the transformation of early LTP into late
      LTP. The results contribute to the understanding of the rapid consolidation of
      cellular and possibly systemic memories triggered by stress.

PMID- 16611812
TI  - Controlling the gain of rod-mediated signals in the Mammalian retina.
AB  - Effective sensory processing requires matching the gain of neural responses to
      the range of signals encountered. For rod vision, gain controls operate at light
      levels at which photons arrive rarely at individual rods, light levels too low to
      cause adaptation in rod phototransduction. Under these conditions, adaptation
      within a conserved pathway in mammalian retina maintains sensitivity as light
      levels change. To relate retinal signals to behavioral work on detection at low
      light levels, we measured how background light affects the gain and noise of
      primate ganglion cells. To determine where and how gain is controlled, we tracked
      rod-mediated signals across the mouse retina. These experiments led to three main
      conclusions: (1) the primary site of adaptation at low light levels is the
      synapse between rod bipolar and AII amacrine cells; (2) cellular noise after the
      gain control is nearly independent of background intensity; and (3) at low
      backgrounds, noise in the circuitry, rather than rod noise or fluctuations in
      arriving photons, limits ganglion cell sensitivity. This work provides
      physiological insights into the rich history of experiments characterizing how
      rod vision avoids saturation as light levels increase.

PMID- 16611813
TI  - Separate populations of receptor cells and presynaptic cells in mouse taste buds.
AB  - Taste buds are aggregates of 50-100 cells, only a fraction of which express genes
      for taste receptors and intracellular signaling proteins. We combined functional
      calcium imaging with single-cell molecular profiling to demonstrate the existence
      of two distinct cell types in mouse taste buds. Calcium imaging revealed that
      isolated taste cells responded with a transient elevation of cytoplasmic Ca2+ to
      either tastants or depolarization with KCl, but never both. Using single-cell
      reverse transcription (RT)-PCR, we show that individual taste cells express
      either phospholipase C beta2 (PLCbeta2) (an essential taste transduction
      effector) or synaptosomal-associated protein 25 (SNAP25) (a key component of
      calcium-triggered transmitter exocytosis). The two functional classes revealed by
      calcium imaging mapped onto the two gene expression classes determined by single
      cell RT-PCR. Specifically, cells responding to tastants expressed PLCbeta2,
      whereas cells responding to KCl depolarization expressed SNAP25. We demonstrate
      this by two methods: first, through sequential calcium imaging and single-cell RT
      PCR; second, by performing calcium imaging on taste buds in slices from
      transgenic mice in which PLCbeta2-expressing taste cells are labeled with green
      fluorescent protein. To evaluate the significance of the SNAP25-expressing cells,
      we used RNA amplification from single cells, followed by RT-PCR. We show that
      SNAP25-positive cells also express typical presynaptic proteins, including a
      voltage-gated calcium channel (alpha1A), neural cell adhesion molecule, synapsin
      II, and the neurotransmitter-synthesizing enzymes glutamic acid decarboxylase and
      aromatic amino acid decarboxylase. No synaptic markers were detected in PLCbeta2
      cells by either amplified RNA profiling or by immunocytochemistry. These data
      demonstrate the existence of at least two molecularly distinct functional classes
      of taste cells: receptor cells and synapse-forming cells.

PMID- 16611814
TI  - Estimation of the timing of human visual perception from magnetoencephalography.
AB  - To explore the timing and the underlying neural dynamics of visual perception, we
      analyzed the relationship between the manual reaction time (RT) to the onset of a
      visual stimulus and the time course of the evoked neural response simultaneously
      measured by magnetoencephalography (MEG). The visual stimuli were a transition
      from incoherent to coherent motion of random dots and an onset of a chromatic
      grating from a uniform field, which evoke neural responses in different cortical
      sites. For both stimuli, changes in median RT with changing stimulus strength
      (motion coherence or chromatic contrast) were accurately predicted, with a
      stimulus-independent postdetection delay, from the time that the temporally
      integrated MEG response crossed a threshold (integrator model). In comparison,
      the prediction of RT was less accurate from the peak MEG latency, or from the
      time that the nonintegrated MEG response crossed a threshold (level detector
      model). The integrator model could also account for, at least partially,
      intertrial changes in RT or in perception (hit/miss) to identical stimuli.
      Although we examined MEG-RT relationships mainly for data averaged over trials,
      the integrator model could show some correlations even for single-trial data. The
      model predictions deteriorated when only early visual responses presumably
      originating from the striate cortex were used as the input to the integrator
      model. Our results suggest that the perceptions for visual stimulus appearances
      are established in extrastriate areas [around MT (middle temporal visual area)
      for motion and around V4 (fourth visual area) for color] approximately 150-200 ms
      before subjects manually react to the stimulus.

PMID- 16611815
TI  - Control of mammalian cochlear amplification by chloride anions.
AB  - Chloride ions have been hypothesized to interact with the membrane outer hair
      cell (OHC) motor protein, prestin on its intracellular domain to confer voltage
      sensitivity (Oliver et al., 2001). Thus, we hypothesized previously that
      transmembrane chloride movements via the lateral membrane conductance of the
      cell, GmetL, could serve to underlie cochlear amplification in the mammal. Here,
      we report on experimental manipulations of chloride-dependent OHC motor activity
      in vitro and in vivo. In vitro, we focused on the signature electrical
      characteristic of the motor, the nonlinear capacitance of the cell. Using the
      well known ototoxicant, salicylate, which competes with the putative anion
      binding or interaction site of prestin to assess level-dependent interactions of
      chloride with prestin, we determined that the resting level of chloride in OHCs
      is near or below 10 mm, whereas perilymphatic levels are known to be
      approximately 140 mm. With this observation, we sought to determine the effects
      of perilymphatic chloride level manipulations of basilar membrane amplification
      in the living guinea pig. By either direct basolateral perfusion of the OHC with
      altered chloride content perilymphatic solutions or by the use of tributyltin, a
      chloride ionophore, we found alterations in OHC electromechanical activity and
      cochlear amplification, which are fully reversible. Because these anionic
      manipulations do not impact on the cation selective stereociliary process or the
      endolymphatic potential, our data lend additional support to the argument that
      prestin activity dominates the process of mammalian cochlear amplification.

PMID- 16611816
TI  - Semaphorin-1a functions as a guidance receptor in the Drosophila visual system.
AB  - The evolutionarily conserved Semaphorin family proteins are well known axon
      guidance ligands that mediate both attractive and repulsive responses in
      invertebrates and vertebrates. In this study, we show that the Drosophila
      Semaphorin-1a (Sema1a), a transmembrane Semaphorin, is required cell autonomously
      in adult photoreceptor (R-cell) axons for the establishment of an appropriate
      topographic termination pattern in the optic lobe. Loss of sema1a disrupts the
      association of neighboring R-cell growth cones leading to defects in local
      termination pattern, whereas overexpression of sema1a induces the hyper
      fasciculation of R-cell axons. The function of Sema1a in R-cell axon guidance
      absolutely requires its cytoplasmic domain. We propose that Sema1a functions as a
      receptor in regulating R-cell axon guidance in the Drosophila visual system.

PMID- 16611817
TI  - Requirement of Akt to mediate long-term synaptic depression in Drosophila.
AB  - Drosophila larval neuromuscular junction (NMJ) is a well established preparation
      enabling quantitative analyses of synaptic physiology at identifiable synapses.
      Here, we report the first characterization of synaptic long-term depression (LTD)
      at the Drosophila NMJ. LTD can be reliably induced by specific patterns of
      tetanic stimulation, and the level of LTD depends on both stimulus frequency and
      Ca2+ concentration. We provide evidence that LTD is likely a result of
      presynaptic changes. Through screening of targeted mutants with defects in memory
      or signal transduction pathways, we found that LTD is strongly reduced in the akt
      mutants. This defect can be rescued by acutely induced expression of the normal
      akt transgene, suggesting that altered LTD is not attributable to developmental
      abnormalities and that Akt is critical for the induction of LTD. Our study also
      indicates that the molecular mechanisms of LTD are distinct from that of short
      term synaptic plasticity, because akt mutants showed normal short-term
      facilitation and posttetanic potentiation, whereas LTD was unaffected in mutants
      that exhibit defective short-term synaptic plasticity, such as dunce and
      rutabaga. The characterization of LTD allows genetic analysis of the molecular
      mechanisms of long-term synaptic plasticity in Drosophila and provides an
      additional assay for studying functions of genes pertaining to synaptic and
      behavioral plasticity.

PMID- 16611818
TI  - Cholinergic modulation of synaptic transmission and postsynaptic excitability in
      the rat gracilis dorsal column nucleus.
AB  - Somatosensory information, conveyed through the gracilis nucleus (GN), is
      regulated by descending corticofugal (CF) glutamatergic fibers. In addition, the
      GN receives cholinergic inputs with still unclear source and functional
      significance. Using both the in vitro slice and intracellular recording with
      sharp and patch electrodes and in vivo extracellular single-unit recordings, we
      analyzed the effects of activation of cholinergic receptors on synaptic,
      intrinsic, and functional properties of rat GN neurons. The cholinergic agonist
      carbamilcholine-chloride [carbachol (CCh); 1-10 microM] in vitro (1) induced
      presynaptic inhibition of EPSPs evoked by both dorsal column and CF stimulation,
      (2) increased postsynaptic excitability, and (3) amplified the spike output of GN
      neurons. The inhibition by atropine (1 microM) and pirenzepine (10 microM) of all
      presynaptic and postsynaptic effects of CCh suggests actions through muscarinic
      M1 receptors. The above effects were insensitive to nicotinic antagonists. We
      searched the anatomical origin of the cholinergic projection to the GN throughout
      the hindbrain and forebrain, and we found that the cholinergic fibers originated
      mainly in the pontine reticular nucleus (PRN). Electrical stimulation of the PRN
      amplified sensory responses in the GN in vivo, an effect prevented by topical
      application of atropine. Our results demonstrate for the first time that
      cholinergic agonists induce both presynaptic and postsynaptic effects on GN
      neurons and suggest an important regulatory action of inputs from cholinergic
      neuronal groups in the pontine reticular formation in the functional control of
      somatosensory information flow in the GN.

PMID- 16611819
TI  - Persistent responses to brief stimuli: feedback excitation among brainstem
      neurons.
AB  - The ability of brief stimuli to trigger prolonged neuronal activity is a
      fundamental requirement in nervous systems, common to motor responses and short
      term memory. Bistable membrane properties and network feedback excitation have
      both been proposed as suitable mechanisms to sustain such persistent responses.
      There is now good experimental evidence for membrane bistability. In contrast,
      the long-standing hypotheses based on positive feedback excitation have yet to be
      supported by direct evidence for mutual excitatory connections between
      appropriate neurons. In young frog tadpoles (Xenopus), we show that a small
      region of caudal hindbrain and rostral spinal cord is sufficient to generate
      prolonged swimming in response to a brief stimulus. We used paired whole-cell
      patch recordings to identify hindbrain neurons in this region that actively
      excite spinal neurons to drive sustained swimming. We show directly that some of
      these hindbrain neurons make reciprocal excitatory connections with each other.
      We use a population model of the hindbrain network to illustrate how feedback
      excitation can provide a robust mechanism to generate persistent responses. Our
      recordings provide direct evidence for feedback excitation among neurons within a
      network that drives a prolonged response. Its presence in a lower brain region
      early in development suggests that it is a basic feature of neuronal network
      design.

PMID- 16611820
TI  - Opioid receptors in the nucleus accumbens regulate attentional learning in the
      blocking paradigm.
AB  - Fear learning depends on prediction error, or the discrepancy between the actual
      and expected outcome of a conditioning trial. These experiments used blocking and
      unblocking designs to study the role of opioid receptors in the nucleus accumbens
      (Acb) in predictive fear learning. Previous fear conditioning to a context
      blocked later fear conditioning to a conditioned stimulus (CS) in that context.
      Fear learning proceeded normally (i.e., unblocking occurred) if the CS signaled a
      more intense footshock than was used during previous context conditioning.
      Blocking and unblocking were mediated by Acb opioid receptors. Acb
      microinjections of a nonselective opioid receptor agonist prevented blocking,
      whereas a nonselective antagonist prevented unblocking. Examination of the
      associative mechanism for blocking and unblocking revealed that Acb opioid
      receptors mediate indirect predictive learning by controlling learned variations
      in attention. Mu-opioid and kappa-opioid receptors contribute to this learned
      regulation of attention because Acb microinjections of a mu-opioid receptor
      agonist impaired, whereas a kappa-opioid receptor agonist facilitated, blocking.
      Acb microinjections of a mu-opioid receptor antagonist also prevented unblocking.
      Microinjections of a delta-opioid receptor agonist or antagonist were without
      effect on blocking and unblocking. Our data show that the Acb mediates
      attentional selection between competing predictors of motivationally significant
      events to enable learning about the best predictor of such events at the expense
      of worse predictors. During fear learning, Acb mu-opioid receptors upregulate
      attention to conditioned stimuli that are predictive of shock, whereas kappa
      opioid receptors downregulate attention to conditioned stimuli that are redundant
      or noninformative predictors of shock.

PMID- 16611821
TI  - Effects of musical experience on different components of MEG responses elicited
      by sequential piano-tones and chords.
AB  - Magnetoencephalographic (MEG) studies have revealed enhancement of neural
      activity of the N1m response of auditory evoked fields in long-term trained
      musicians, reflecting neuroplastic modification of the representation of the
      auditory cortex. In contrast, the amplitude of the P2 response of auditory evoked
      potentials is modified by musical experience, with no alteration of N1. Here, we
      performed a comprehensive MEG study using stimulation of successive musical
      instrument tones to examine how the neural activities of different MEG responses
      are modified in long-term experienced musicians who commenced musical lessons at
      ages of approximately 5 years and had continued to practice. The dipole moment of
      the P2m response occurring at 160-180 ms was significantly enlarged in musicians
      compared with that in individuals who had not received musical lessons. The
      enlargement was found for the dipole moment of N1m occurring at 100-120 ms in a
      restricted condition but not for the moment of P1m at 50-60 ms. Furthermore, the
      dipole moment of P2m for successive stimuli, normalized by the moment for the
      first stimulus, was significantly larger for chord tones than single tones and
      was significantly larger in the musicians than controls. These results suggest
      that the P2m response is susceptible to be modified by musical training in a
      period of neural maturation, with a short refractory period of neural activity
      for the auditory input of composite tones. The P2m activity may be specialized to
      the processing of multifrequency sounds, such as musical timbre consisting of
      abundant harmonics.

PMID- 16611822
TI  - Tubulin-mediated binding of human immunodeficiency virus-1 Tat to the
      cytoskeleton causes proteasomal-dependent degradation of microtubule-associated
      protein 2 and neuronal damage.
AB  - One of the hallmarks of human immunodeficiency virus (HIV)-1 associated pathology
      in the CNS is deterioration of neuronal processes. Although there is mounting
      evidence of neuronal toxicity and cell death induced by the HIV-1 transactivating
      factor Tat, the molecular events linked directly to its detrimental effect on
      neuronal cells remain unclear. In this study, we used rat embryonic cortical
      neurons and demonstrated that Tat causes rapid degradation of microtubule
      associated protein 2 (MAP2) and the collapse of cytoskeletal filaments. The
      mechanism of Tat action on MAP2 stability involved Tat-mediated translocation of
      the proteasome to the site of microtubule filaments. Immunohistochemical analysis
      of clinical samples from patients with HIV encephalopathy further revealed a
      significant decrease in MAP2 with predominant cytoplasmic 20S in cortical neurons
      near microglial nodules. These findings indicate a novel mechanism for the action
      of Tat on neuronal cells. It involves proteasome-mediated MAP2 degradation and
      may account for the loss of MAP2 and neuronal damage observed in the brain of
      AIDS patients with neurological dysfunctions.

PMID- 16611823
TI  - Medial frontal cortex activity and loss-related responses to errors.
AB  - Making an error elicits activity from brain regions that monitor performance,
      especially the medial frontal cortex (MFC). However, uncertainty exists about
      whether the posterior or anterior/rostral MFC processes errors and to what degree
      affective responses to errors are mediated in the MFC, specifically the rostral
      anterior cingulate cortex (rACC). To test the hypothesis that rACC mediates a
      type of affective response, we conceptualized affect in response to an error as a
      reaction to loss and amplified this response with a monetary penalty. While
      subjects performed a cognitive interference task during functional magnetic
      resonance imaging, hemodynamic activity in the rACC was significantly greater
      when subjects lost money as a result of an error compared with errors that did
      not lead to monetary loss. A significant interaction between the incentive
      conditions and error events demonstrated that the effect was not merely
      attributable to working harder to win (or not lose) money, although an effect of
      motivation was noted in the mid-MFC. Activation foci also occurred in similar
      regions of the posterior MFC for error and interference processing, which were
      not modulated by the incentive conditions. However, at the level of the
      individual subject, substantial functional variability occurred along the MFC
      during error processing, including foci in the rostral/anterior extent of the MFC
      not appearing in the group analysis. The findings support the hypothesis that the
      rostral extent of the MFC (rACC) processes loss-related responses to errors, and
      individual differences may account for some of the reported variation of error
      related foci in the MFC.

PMID- 16611824
TI  - Impaired sequential egocentric and allocentric memories in forebrain-specific
      NMDA receptor knock-out mice during a new task dissociating strategies of
      navigation.
AB  - The hippocampus is considered to play a role in allocentric but not in egocentric
      spatial learning. How does this view fit with the emerging evidence that the
      hippocampus and possibly related cortical areas are necessary for episodic-like
      memory, i.e., in all situations in which events need to be spatially or
      sequentially organized? Are NMDA receptor-dependent mechanisms crucial for the
      acquisition of spatiotemporal relationships? To address this issue, we used knock
      out (KO) mice lacking hippocampal CA1 NMDA receptors and presenting a reduction
      of these receptors in the deep cortical layers (NR1-KO mice). A new task (the
      starmaze) was designed, allowing us to distinguish allocentric and sequential
      egocentric memories. NR1-KO mice were impaired in acquiring both types of memory.
      Our findings suggest that memories composed of multiple spatiotemporal events
      require intact NMDA receptors-dependent mechanisms in CA1 and possibly in the
      deep cortical layers.

PMID- 16611825
TI  - The unique 473HD-Chondroitinsulfate epitope is expressed by radial glia and
      involved in neural precursor cell proliferation.
AB  - Neural stem cells have been documented in both the developing and the mature
      adult CNSs of mammals. This cell population holds a considerable promise for
      therapeutical applications in a wide array of CNS diseases. Therefore,
      universally applicable strategies for the purification of this population to
      further its cell biological characterization are sought. Here, we report that the
      unique chondroitin sulfate epitope recognized by the monoclonal antibody 473HD is
      surface expressed on actively cycling, multipotent progenitor cells of the
      developing telencephalon with radial glia-like properties. When used for
      immunopanning, the antibody enriched at least threefold for neural
      stem/progenitor cells characterized by the ability to self-renew as neurospheres
      that generated all major neural lineages in differentiation assays. In contrast,
      the 473HD-depleted cell fraction was mostly devoid of neurosphere-forming cells.
      The isolation of 473HD-positive adult multipotent progenitors from the
      subependymal zone of the lateral ventricle wall revealed a substantial overlap
      with the known adult neural stem cell marker LewisX. When the chondroitin
      sulfates were removed from immunoselected 473HD-positive neural stem/progenitor
      cell surfaces by chondroitinase ABC treatment or perturbed by the monoclonal
      antibody 473HD that recognizes the unique DSD-1 chondroitin sulfate epitope, the
      generation of neurospheres was significantly reduced. Thus, the 473HD epitope
      could not only be used for the isolation of multipotent neural progenitors during
      forebrain development as well as from the adult neurogenic niche but may also
      constitute a functionally important entity of the neural stem cell niche.

PMID- 16611826
TI  - Seizures accelerate functional integration of adult-generated granule cells.
AB  - In humans and experimental animals, structural and functional changes in neural
      circuits can accompany the development of epilepsy. In the dentate gyrus,
      seizures enhance adult neurogenesis, but it is unclear to what extent newborn
      granule cells participate in seizure-induced synaptic reorganization. During the
      first weeks of their existence, mouse newborn granule cells labeled with enhanced
      green fluorescent protein have only short dendrites that lack excitatory input.
      We report that pilocarpine-induced seizures accelerated the morphological
      development of labeled granule cells, causing their dendrites to extend through
      the molecular layer. In whole-cell recordings 5-16 d after seizure induction,
      perforant-path stimulation now evoked glutamatergic input to newborn granule
      cells. These synaptic responses were mediated by monosynaptic as well as
      recurrent polysynaptic input. Thus, seizures facilitated functional integration
      of adult-generated granule cells. One month later, subsequent generations of
      newborn cells also showed alterations in dendrite morphology, suggesting
      persistent effects of seizures on granule cell maturation. The sensitivity of
      newborn granule cells to seizures could contribute to hyperexcitability during
      the latent period.

PMID- 16611827
TI  - Estrogen induces estrogen receptor alpha-dependent cAMP response element-binding
      protein phosphorylation via mitogen activated protein kinase pathway in basal
      forebrain cholinergic neurons in vivo.
AB  - In addition to classical genomic mechanisms, estrogen also exerts nonclassical
      effects via a signal transduction system on neurons. To study whether estrogen
      has a nonclassical effect on basal forebrain cholinergic system, we measured the
      intensity of cAMP response element-binding protein (CREB) phosphorylation (pCREB)
      in cholinergic neurons after administration of 17beta-estradiol to ovariectomized
      (OVX) mice. A significant time-dependent increase in the number of pCREB-positive
      cholinergic cells was detected after estrogen administration in the medial septum
      diagonal band (MS-DB) and the substantia innominata (SI). The increase was first
      observed 15 min after estrogen administration. The role of classical estrogen
      receptors (ERs) was evaluated using ER knock-out mice in vivo. The estrogen
      induced CREB phosphorylation in cholinergic neurons was present in ERbeta knock
      out mice but completely absent in ERalpha knock-out mice in MS-DB and SI. A
      series of in vitro studies demonstrated that estrogen acted directly on
      cholinergic neurons. Selective blockade of the mitogen activated protein kinase
      (MAPK) pathway in vivo completely prevented estrogen-induced CREB phosphorylation
      in cholinergic neurons in MS-DB and SI. In contrast, blockade of protein kinase A
      (PKA) was effective only in SI. Finally, studies in intact female mice revealed
      levels of CREB phosphorylation within cholinergic neurons that were similar to
      those of estrogen-treated OVX mice. These observations demonstrate an ERalpha
      mediated nonclassical effect of estrogen on the cholinergic neurons and that
      these actions are present under physiological conditions. They also reveal the
      role of MAPK and PKA-MAPK pathway activation in nonclassical estrogen signaling
      in the basal forebrain cholinergic neurons in vivo.

PMID- 16611828
TI  - Essential role of the hippocampal formation in rapid learning of higher-order
      sequential associations.
AB  - Evidence from studies of amnesia and functional imaging in humans suggest that
      the medial temporal lobe is involved in the learning of higher-order sequences
      during acquisition of serial reaction time (SRT) tasks. However, these studies
      have not clarified whether the hippocampal formation specifically is essential to
      this type of learning. Here, we developed a rodent model of the SRT task to
      examine the specific roles of the hippocampal formation in learning first- and
      second-order conditional sequences. Selective hippocampal formation lesions
      speeded performance and impaired accuracy on both first- and second-order
      sequences. Additionally, whereas controls distinguished the sequences based on
      their complexity alone, animals with hippocampal lesions initially differentiated
      sequences only by their length. Over multiple sessions, hippocampal rats
      gradually differentiated sequences by their complexity and not length, similar to
      control subjects. These findings indicate that the hippocampal formation itself
      plays an essential role in rapid acquisition of higher-order sequence
      representations. Extrahippocampal systems can also acquire complex sequential
      representations, albeit via a gradual learning mechanism.

PMID- 16611829
TI  - Separation of mu-opioid receptor desensitization and internalization: endogenous
      receptors in primary neuronal cultures.
AB  - A close relationship between desensitization and internalization of mu-opioid
      receptors (MORs) has been proposed based on differential actions of series of
      agonists. The role that these two processes have in the development of tolerance
      and dependence to opioids has been a controversial subject that has been studied
      in a variety of model systems. Here, we examine desensitization and
      internalization of endogenous MORs simultaneously in primary cultures of locus
      ceruleus neurons using fluorescently tagged peptide agonists. With the use of two
      fluorescent opioid peptides, dermorphin-Bodipy Texas Red and dermorphin-Alexa594
      (Derm-A594), desensitization was measured electrophysiologically and trafficking
      was followed by the accumulation of intracellular fluorescent puncta. Blocking
      endocytosis with concanavalin A eliminated the accumulation of fluorescent puncta
      but desensitization induced by Derm-A594 was unaffected. Likewise, after
      treatment with concanavalin A, there was no change in either desensitization or
      recovery from desensitization induced by [Met]5enkephalin. The results
      demonstrate that desensitization and the recovery from desensitization are not
      dependent on receptor internalization and suggest that the activity of endogenous
      MORs in primary neurons can be modulated at the level of the plasma membrane.

PMID- 16611830
TI  - Rapid taste responses in the gustatory cortex during licking.
AB  - Rapid tastant detection is necessary to prevent the ingestion of potentially
      poisonous compounds. Behavioral studies have shown that rats can identify
      tastants in approximately 200 ms, although the electrophysiological correlates
      for fast tastant detection have not been identified. For this reason, we
      investigated whether neurons in the primary gustatory cortex (GC), a cortical
      area necessary for tastant identification and discrimination, contain sufficient
      information in a single lick cycle, or approximately 150 ms, to distinguish
      between tastants at different concentrations. This was achieved by recording
      neural activity in GC while rats licked four times without a liquid reward, and
      then, on the fifth lick, received a tastant (FR5 schedule). We found that 34% (61
      of 178) of GC units were chemosensitive. The remaining neurons were activated
      during some phase of the licking cycle, discriminated between reinforced and
      unreinforced licks, or processed task-related information. Chemosensory neurons
      exhibited a latency of 70-120 ms depending on concentration, and a temporally
      precise phasic response that returned to baseline in tens of milliseconds.
      Tastant-responsive neurons were broadly tuned and responded to increasing tastant
      concentrations by either increasing or decreasing their firing rates. In
      addition, some responses were only evoked at intermediate tastant concentrations.
      In summary, these results suggest that the gustatory cortex is capable of
      processing multimodal information on a rapid timescale and provide the
      physiological basis by which animals may discriminate between tastants during a
      single lick cycle.

PMID- 16611831
TI  - Associative memory stored by functional novel pathway rather than modifications
      of preexisting neuronal pathways.
AB  - Associative conditioning involves changes in the processing pathways activated by
      sensory information to link the conditioned stimulus (CS) to the conditioned
      behavior. Thus, conditioning can recruit neuronal elements to form new pathways
      for the processing of the CS and/or can change the strength of existing pathways.
      Using a behavioral and systems level electrophysiological approach on a tractable
      invertebrate circuit generating feeding in the mollusk Lymnaea stagnalis, we
      identified three independent pathways for the processing of the CS amyl acetate
      used in appetitive conditioning. Two of these pathways, one suppressing and the
      other stimulating feeding, mediate responses to the CS in naive animals. The
      effects of these two pathways on feeding behavior are unaltered by conditioning.
      In contrast, the CS response of a third stimulatory pathway is significantly
      enhanced after conditioning, becoming an important contributor to the overall CS
      response. This is unusual because, in most of the previous examples in which
      naive animals already respond to the CS, memory formation results from changes in
      the strength of pathways that mediate the existing response. Here, we show that,
      in the molluscan feeding system, both modified and unmodified pathways are
      activated in parallel by the CS after conditioning, and it is their integration
      that results in the conditioned response.

PMID- 16611832
TI  - Passive calcium leak via translocon is a first step for iPLA2-pathway regulated
      store operated channels activation.
AB  - Calcium concentration within the endoplasmic reticulum (ER) plays an essential
      role in cell physiopathology. One of the most enigmatic mechanisms responsible
      for Ca2+ concentration in the ER is passive calcium leak. Previous studies have
      shown that the translocon complex is permeable to calcium. However, the
      involvement of the translocon in the passive calcium leak has not been directly
      demonstrated. Furthermore, the question whether the passive store depletion via
      the translocon could activate SOC (store operated channels) replenishing the ER,
      remains still unresolved. In this study, for the first time, we show that
      thapsigargin and calcium chelators deplete ER via translocon. Indeed, using
      confocal imaging, we demonstrate that when the number of opened translocons was
      lowered neither thapsigargin nor calcium chelators could induce ER store
      depletion. We also demonstrate that calcium leakage occurring via the translocon
      activates store-operated current, which is, by its kinetic and pharmacology,
      similar to that evoked by thapsigargin and EGTA (but not IP3), thus highlighting
      our hypothesis that calcium leakage via the translocon is a first step for
      activation of the specific iPLA2-regulated SOC. As the translocon is present in
      yeast and mammalian cells, our findings suggest that translocon-related calcium
      signaling is a common phenomenon.

PMID- 16611833
TI  - Adventitia contribution in vascular tone: insights from adventitia-derived cells
      in a tissue-engineered human blood vessel.
AB  - Whether the adventitia component of blood vessels directly participates in the
      regulation of vascular tone remains to be demonstrated. We have recently
      developed a human tissue-engineered blood vessel comprising the three tunicae of
      a native blood vessel using the self-assembly approach. To investigate the role
      of the adventitia in the modulation of vascular tone, this tissue-engineering
      method was used to produce three vascular constructs from cells explanted and
      proliferated from donor vessel tunicae 1) an adventitia + a media, or only 2) an
      adventitia, or 3) a media. The vasoconstriction responses of these 3 constructs
      to endothelin, the most potent vasopressor known up-to-date, as well as to
      nonselective and selective agonists and antagonists, were compared. The
      adventitia contracted to endothelin-1, -2, whereas the media and the
      media+adventitia contracted to all three endothelins. Endothelin-induced
      contraction of the adventitia was dependent on ET(A) receptors, whereas that of
      the media and the adventitia+media was ET(A) and ET(B) receptor-dependent. RT-PCR
      studies corroborated these results. SNP induced a dose-dependent relaxation of
      the three tissue constructs. We also demonstrated that the endothelin-converting
      enzyme, responsible for the formation of the active endothelin peptides, was
      present and functional in the adventitia. In conclusion, this is the first direct
      demonstration that the adventitia has the capacity to contract and relax in
      response to vasoactive factors. The present study suggests that the adventitia of
      a blood vessel could play a greater role than expected in the modulation of blood
      vessel tone.

PMID- 16611834
TI  - Leptin down-regulates insulin action through phosphorylation of serine-318 in
      insulin receptor substrate 1.
AB  - Insulin resistance in skeletal muscle is found in obesity and type 2 diabetes. A
      mechanism for impaired insulin signaling in peripheral tissues is the inhibition
      of insulin action through serine phosphorylation of insulin receptor substrate
      (Irs) proteins that abolish the coupling of Irs proteins to the activated insulin
      receptor. Recently, we described serine-318 as a protein kinase C (PKC)-dependent
      phosphorylation site in Irs1 (Ser-318) activated by hyperinsulinemia. Here we
      show in various cell models that the adipose hormone leptin, a putative mediator
      in obesity-related insulin resistance, promotes phosphorylation of Ser-318 in
      Irs1 by a janus kinase 2, Irs2, and PKC-dependent pathway. Mutation of Ser-318 to
      alanine abrogates the inhibitory effect of leptin on insulin-induced Irs1
      tyrosine phosphorylation and glucose uptake in L6 myoblasts. In C57Bl/6 mice, Ser
      318 phosphorylation levels in muscle tissue were enhanced by leptin and insulin
      administration in lean animals while in diet-induced obesity Ser-318
      phosphorylation levels were already up-regulated in the basal state, and further
      stimulation was diminished. In analogy, in lymphocytes of obese hyperleptinemic
      human subjects basal Ser-318 phosphorylation levels were increased compared to
      lean individuals. During a hyperinsulinemic euglycemic clamp, the increment in
      Ser-318 phosphorylation observed in lean individuals was absent in obese. In
      summary, these data suggest that phosphorylation of Ser-318 in Irs1 mediates the
      inhibitory signal of leptin on the insulin-signaling cascade in obese subjects.

PMID- 16611836
TI  - Twitch and tetanic properties of human thenar motor units paralyzed by chronic
      spinal cord injury.
AB  - Little is known about how human motor units respond to chronic paralysis. Our aim
      was to record surface electromyographic (EMG) signals, twitch forces, and tetanic
      forces from paralyzed motor units in the thenar muscles of individuals (n = 12)
      with chronic (1.5-19 yr) cervical spinal cord injury (SCI). Each motor unit was
      activated by intraneural stimulation of its motor axon using single pulses and
      trains of pulses at frequencies between 5 and 100 Hz. Paralyzed motor units (n =
      48) had small EMGs and weak tetanic forces (n = 32 units) but strong twitch
      forces, resulting in half-maximal force being achieved at a median of only 8 Hz.
      The distributions for cumulative twitch and tetanic forces also separated less
      for paralyzed units than for control units, indicating that increases in
      stimulation frequency made a smaller relative contribution to the total force
      output in paralyzed muscles. Paralysis also induced slowing of conduction
      velocities, twitch contraction times and EMG durations. However, the elevated
      ratios between the twitch and the tetanic forces, but not contractile speed,
      correlated significantly with the extent to which unit force summated in response
      to different frequencies of stimulation. Despite changes in the absolute values
      of many electrical and mechanical properties of paralyzed motor units, most of
      the distributions shifted uniformly relative to those of thenar units obtained
      from control subjects. Thus human thenar muscles paralyzed by SCI retain a
      population of motor units with heterogeneous contractile properties because
      chronic paralysis influenced all of the motor units similarly.

PMID- 16611835
TI  - Orexin neurons are directly and indirectly regulated by catecholamines in a
      complex manner.
AB  - We reported elsewhere that orexin neurons are directly hyperpolarized by
      noradrenaline (NA) and dopamine. In the present study, we show that NA, dopamine,
      and adrenaline all directly hyperpolarized orexin neurons. This response was
      inhibited by the alpha2 adrenergic receptor (alpha2-AR) antagonist, idazoxan or
      BRL44408, and was mimicked by the alpha2-AR-selective agonist, UK14304. A low
      concentration of Ba2+ inhibited NA-induced hyperpolarization, which suggests that
      activation of G protein coupled inward rectifier potassium channels is involved
      in the response. In the presence of a high concentration of idazoxan, NA induced
      depolarization or inward current. This response was inhibited by alpha1-AR
      antagonist, prazosin, which suggests the existence of alpha1-ARs on the orexin
      neurons along with alpha2-AR. We also examined the effects of NA on glutamatergic
      and GABAergic synaptic transmission. NA application dramatically increased the
      frequency and amplitude of spontaneous inhibitory synaptic currents (sIPSCs) and
      inhibited excitatory synaptic currents (sEPSCs) in orexin neurons; however, NA
      decreased the frequency of miniature EPSCs (mEPSCs) and IPSCs and the amplitude
      of evoked EPSCs and IPSCs through the alpha2-AR, because the NA response on mPSCs
      was inhibited by idazoxan. These results suggest that the NA-induced increase in
      sIPSC frequency and amplitude is mediated via alpha1-ARs on the somata of
      GABAergic neurons that innervate the orexin neurons. Calcium imaging using
      orexin/YC2.1 transgenic mouse brain revealed that NA-induced inhibition of orexin
      neurons is not altered by sleep deprivation or circadian time in mice. The
      evidence presented here revealed that orexin neurons are regulated by
      catecholamines in a complex manner.

PMID- 16611837
TI  - A-type K+ current of dopamine and GABA neurons in the ventral tegmental area.
AB  - A-type K(+) current (I(A)) is a rapidly inactivating voltage-dependent potassium
      current which can regulate the frequency of action potential (AP) generation.
      Increased firing frequency of ventral tegmental area (VTA) neurons is associated
      with the reinforcing effects of some drugs of abuse like nicotine and ethanol. In
      the present study, we classified dopamine (DA) and GABA VTA neurons, and
      investigated I(A) properties and the physiological role of I(A) in these neurons
      using conventional whole cell current- and voltage-clamp recording. DA VTA
      neurons had a mean firing frequency of 3.5 Hz with a long AP duration. GABA VTA
      neurons had a mean firing frequency of 16.7 Hz with a short AP duration. For I(A)
      properties, the voltage-dependence of steady-state I(A) activation and
      inactivation was similar in DA and GABA VTA neurons. I(A) inactivation was
      significantly faster and became faster at positive voltages in GABA neurons than
      DA neurons. Recovery from inactivation was significantly faster in DA neurons
      than GABA neurons. I(A) current density at full recovery was significantly larger
      in DA neurons than GABA neurons. In DA and GABA VTA neurons, latency to the first
      AP after the recovery from membrane hyperpolarization (repolarization latency)
      was measured. Longer repolarization latency was accompanied by larger I(A)
      current density in DA VTA neurons, compared with GABA VTA neurons. We suggest
      that I(A) contributes more to the regulation of AP generation in DA VTA neurons
      than in GABA VTA neurons.

PMID- 16611838
TI  - Kinetics of activity-evoked pH transients and extracellular pH buffering in rat
      hippocampal slices.
AB  - The kinetics of activity-dependent, extracellular alkaline transients, and the
      buffering of extracellular pH (pH(e)), were studied in rat hippocampal slices
      using a fluorescein-dextran probe. Orthodromic stimuli generated alkaline
      transients < or = 0.05 pH units that peaked in 273 +/- 26 ms and decayed with a
      half-time of 508 +/- 43 ms. Inhibition of extracellular carbonic anhydrase (ECA)
      with benzolamide increased the rate of rise by 25%, doubled peak amplitude, and
      prolonged the decay three- to fourfold. The slow decay in benzolamide allowed
      marked temporal summation, resulting in a severalfold increase in amplitude
      during long stimulus trains. Addition of exogenous carbonic anhydrase reduced the
      rate of rise, halved the peak amplitude, but had no effect on the normalized
      decay. A simulation of extracellular buffering kinetics generated recoveries from
      a base load consistent with the observed decay of the alkaline transient in the
      presence of benzolamide. Under control conditions, the model approximated the
      observed decays with an acceleration of the CO2 hydration-dehydration reactions
      by a factor of 2.5. These data suggest low endogenous ECA activity, insufficient
      to maintain equilibrium during the alkaline transients. Disequilibrium implies a
      time-dependent buffering capacity, with a CO2/HCO3- contribution that is small
      shortly after a base load. It is suggested that within 100 ms, extracellular
      buffering capacity is about 1% of the value at equilibrium and is provided mainly
      by phosphate. Accordingly, in the time frame of synaptic transmission, small base
      loads would generate relatively large changes in interstitial pH.

PMID- 16611839
TI  - Selective inhibition of spontaneous but not Ca2+ -dependent release machinery by
      presynaptic group II mGluRs in rat cerebellar slices.
AB  - Two main forms of neurotransmitter release are known: action potential-evoked and
      spontaneous release. Action potential-evoked release depends on Ca2+ entry
      through voltage-gated Ca2+ channels, whereas spontaneous release is thought to be
      Ca2+ -independent. Generally, spontaneous and action potential-evoked release are
      believed to use the same release machinery to release neurotransmitter. This
      study shows, using the whole cell patch-clamp technique in rat cerebellar slices,
      that at the interneuron- Purkinje cell synapse activation of presynaptic group II
      metabotropic glutamate receptors suppresses spontaneous GABA release through a
      mechanism independent of voltage-gated Ca2+ channels, store-operated Ca2+
      channels, and Ca2+ release from intracellular Ca2+ stores, suggesting that the
      metabotropic receptors target the release machinery directly. Voltage gated Ca2+
      channel-independent release following increased presynaptic cAMP production is
      similarly inhibited by these metabotropic receptors. In contrast, both voltage
      gated Ca2+ channel-dependent and presynaptic N-methyl-D-aspartate receptor
      dependent GABA release were unaffected by activation of group II metabotropic
      glutamate receptors. Hence, the mechanisms underlying spontaneous and Ca2+ 
      dependent GABA release are distinct in that only the former is blocked by group
      II metabotropic glutamate receptors. Thus the same neurotransmitter, glutamate,
      can activate or inhibit neurotransmitter release by selecting different receptors
      that target different release machineries.

PMID- 16611840
TI  - Developmental changes in electrophysiological properties and synaptic
      transmission in rat intracardiac ganglion neurons.
AB  - We charted postnatal changes in the intrinsic electrophysiological properties and
      synaptic responses of rat intrinsic cardiac ganglion (ICG) neurons. We developed
      a whole-mount ganglion preparation of the excised right atrial ganglion plexus.
      Using intracellular recordings and nerve stimulation we tested the hypothesis
      that substantial transformations in the intrinsic electrical characteristics and
      synaptic transmission accompany postnatal development. Membrane potential (E(m))
      did not change but time constant (tau) and cell capacitance increased with
      postnatal development. Accordingly, input resistance (R(in)) decreased but
      specific membrane resistance (R(m)) increased postnatally. Comparison of the
      somatic active membrane properties revealed significant changes in electrical
      phenotype. All neonatal neurons had somatic action potentials (APs) with small
      overshoots and small afterhyperpolarizations (AHPs). Adult neurons had somatic
      APs with large overshoots and large AHP amplitudes. The range of AHP duration was
      larger in adults than in neonates. The AP characteristics of juvenile neurons
      resembled those of adults, with the exception of AHP duration, which fell midway
      between neonate and adult values. Phasic, multiply adapting, and tonic evoked
      discharge activities were recorded from ICG neurons. Most neurons displayed
      phasic discharge at each developmental stage. All neurons received excitatory
      synaptic inputs from the vagus or interganglionic nerve trunk(s), the strength of
      which did not change significantly with postnatal age. The changes in the
      electrophysiological properties of the postganglionic neuron suggest that
      increased complexity of parasympathetic regulation of cardiac function
      accompanies postnatal development.

PMID- 16611841
TI  - Galanin modulates neuronal and synaptic properties in the rat supraoptic nucleus
      in a use and state dependent manner.
AB  - The magnocellular neurons of the hypothalamic supraoptic nucleus (SON) synthesize
      and secrete oxytocin (OXT) and vasopressin (AVP) from their dendrites. These
      peptides, and several other neurotransmitters, have been shown to modulate
      afferent glutamatergic neurotransmission in the SON. The neuropeptide, galanin
      (GAL) is also localized in SON magnocellular neurons and in afferent fibers in
      the nucleus. We show that GAL dose-dependently reduces evoked excitatory
      postsynaptic currents (eEPSCs), alters paired pulse ratio and decreases mEPSC
      frequency, but not amplitude or decay kinetics in both OXT and AVP neurons. GAL
      therefore modulates excitatory neurotransmission at a likely presynaptic
      receptor. Neither OXT/AVP, GABA(B) nor cannabinoid antagonists blocked this
      effect. A GAL2/3 agonist mimicked GAL's action while GAL1 antagonist did not
      block GAL's effect, suggesting that GAL2/3 receptors mediate the presynaptic
      effect. In nondehydrated rats GAL causes a small postsynaptic response, as
      assessed by input resistance measurements. When the rats were water deprived for
      2 days the presynaptic response to GAL was unaltered; however, the postsynaptic
      decrease in input resistance and hyperpolarization was increased, an effect
      consistent with a previously described increase in GAL1 receptor expression in
      dehydration. A GAL1 receptor antagonist blocked the postsynaptic effects. Last,
      when a train of eEPSCs was elicited, GAL was found to inhibit the earlier events
      in a train but not the latter. This indicates that GAL may modulate a single
      synaptic event more effectively than trains of synaptic inputs, thereby acting as
      a high-pass filter.

PMID- 16611842
TI  - Mitochondrial inhibition prior to oxygen-withdrawal facilitates the occurrence of
      hypoxia-induced spreading depression in rat hippocampal slices.
AB  - Oxygen withdrawal blocks mitochondrial respiration. In rat hippocampal slices,
      this triggers a massive depolarization of CA1 neurons and a negative shift of the
      extracellular DC potential, the characteristic sign of hypoxia-induced spreading
      depression (HSD). To unveil the contribution of mitochondria to the sensing of
      hypoxia and the ignition of HSD, we modified mitochondrial function.
      Mitochondrial uncoupling by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone
      (FCCP, 1 microM) prior to hypoxia hastened the onset and shortened the duration
      of HSD. Blocking mitochondrial ATP synthesis by oligomycin (10 microg/ml) was
      without effect. Inhibition of mitochondrial respiration by rotenone (20 microM),
      diphenyleneiodonium (25 microM), or antimycin A (20 microM) also hastened HSD
      onset and shortened HSD duration. 3-nitropropionic acid (1 mM) increased HSD
      duration. Cyanide (100 microM) hastened HSD onset and increased HSD duration. At
      higher concentrations, cyanide (1 mM), azide (2 mM), and FCCP (10 microM)
      triggered SD episodes on their own. Compared with control HSD, the spatial extent
      of the intrinsic optical signals of cyanide- and azide-induced SDs was more
      pronounced. Monitoring NADH (nicotinamide adenine dinucleotide) and FAD (flavin
      adenine dinucleotide) autofluorescence and mitochondrial membrane potential
      verified the mitochondrial targeting by the drugs used. Except 1 mM cyanide, no
      treatment reduced cellular ATP levels severely and no correlation was found
      between ATP, NADH, or FAD levels and the time to HSD onset. Therefore ATP
      depletion or a cytosolic reducing shift due to NADH/FADH2 accumulation cannot
      serve as a general explanation for the hastening of HSD onset on mitochondrial
      inhibition. Additional redox couples (glutathione) or events downstream of the
      mitochondrial depolarization need to be considered.

PMID- 16611843
TI  - Contribution of M-waves and H-reflexes to contractions evoked by tetanic nerve
      stimulation in humans.
AB  - Tetanic neuromuscular stimulation evokes contractions by depolarizing motor axons
      beneath the stimulating electrodes. However, we have shown that extra torque can
      develop due to the discharge of spinal neurons recruited by the evoked sensory
      volley. The present experiments investigated whether extra torque in the ankle
      plantar- and dorsiflexors was associated with enhanced H-reflexes. The tibial and
      common peroneal nerves were stimulated using 7-s trains (20 Hz for 2 s, 100 Hz
      for 2 s, 20 Hz for 3 s). Extra torque was defined as significantly more torque
      during 20-Hz stimulation after the 100-Hz burst (time2) than before it (time1).
      In 9 of 11 subjects, extra plantarflexion torque developed during stimulation
      just above motor threshold. In these nine subjects, torque increased from 8 to
      13% MVC (time1 to time2), the soleus H-reflex increased from 13 to 19% Mmax and
      the M-wave of approximately 2% Mmax did not change significantly. To evoke extra
      dorsiflexion torque, greater stimulation intensities were required. In 6 of 13
      subjects, extra torque developed at intensities that evoked an M-wave of 5-20%
      Mmax at time1. In these six subjects, torque doubled from 2 to 4% MVC (time1 to
      time2), whereas tibialis anterior (TA) H-reflexes and M-waves did not change
      significantly (H-reflex from 0.8 to 2% Mmax; M-wave from 12 to 14% Mmax). In 7 of
      13 subjects, extra torque developed at higher stimulation intensities (35-65%
      Mmax). In these seven subjects, torque increased from 13 to 20% MVC, whereas TA H
      reflexes and M-waves were not significantly different (H-reflex from 0.7 to 1%
      Mmax; M-wave from 49 to 54% Mmax). Thus enhanced H-reflexes contributed to extra
      plantarflexion, however, other factors generated extra dorsiflexion.

PMID- 16611845
TI  - Changes in mIPSCs and sIPSCs after kainate treatment: possible actions mediated
      by the direct activation of kainate receptors.

PMID- 16611846
TI  - Sciatic chronic constriction injury produces cell-type-specific changes in the
      electrophysiological properties of rat substantia gelatinosa neurons.
AB  - Peripheral nerve injury increases spontaneous action potential discharge in
      spinal dorsal horn neurons and augments their response to peripheral stimulation.
      This "central hypersensitivity, " which relates to the onset and persistence of
      neuropathic pain, reflects spontaneous activity in primary afferent fibers as
      well as long-term changes in the intrinsic properties of the dorsal horn
      (centralization). To isolate and investigate cellular mechanisms underlying
      "centralization," sciatic nerves of 20-day-old rats were subjected to 13-25 days
      of chronic constriction injury (CCI; Mosconi-Kruger polyethylene cuff model).
      Spinal cord slices were then acutely prepared from sham-operated or CCI animals,
      and whole cell recording was used to compare the properties of five types of
      substantia gelatinosa neuron. These were defined as tonic, irregular, phasic,
      transient, or delay according to their discharge pattern in response to
      depolarizing current. CCI did not affect resting membrane potential, rheobase, or
      input resistance in any neuron type but increased the amplitude and frequency of
      spontaneous and miniature excitatory postsynaptic currents (EPSCs) in delay,
      transient, and irregular cells. These changes involved alterations in the action
      potential-independent neurotransmitter release machinery and possible increases
      in the postsynaptic effectiveness of glutamate. By contrast, in tonic cells, CCI
      reduced the amplitude and frequency of spontaneous and miniature EPSCs. Such
      changes may relate to the putative role of tonic cells as inhibitory GABAergic
      interneurons, whereas increased synaptic drive to delay cells may relate to their
      putative role as the excitatory output neurons of the substantia gelatinosa.
      Complementary changes in synaptic excitation of inhibitory and excitatory neurons
      may thus contribute to pain centralization.

PMID- 16611847
TI  - Position information but not force information is used in adapting to changes in
      environmental dynamics.
AB  - This study investigated how movement error is evaluated and used to change
      feedforward commands following a change in the environmental dynamics. In
      particular, we addressed the question of whether only position-error information
      is used or whether information about the force-field direction can also be used
      for rapid adaptation to changes in the environmental dynamics. Subjects learned
      to move in a position-dependent force field (PF) with a parabolic profile and the
      dynamics of a negative spring, which produced lateral force to the left of the
      target hand path. They adapted very rapidly, dramatically reducing lateral error
      after a single trial. Several times during training, the strength of the PF was
      unexpectedly doubled (PF2) for two trials. This again created a large leftward
      deviation, which was greatly reduced on the second PF2 trial, and an aftereffect
      when the force field subsequently returned to its original strength. The
      aftereffect was abolished if the second PF2 trial was replaced by an oppositely
      directed velocity-dependent force field (VF). During subsequent training in the
      VF, immediately after having adapted to the PF, subjects applied a force that
      assisted the force field for approximately 15 trials, indicating that they did
      not use information about the force-field direction. We concluded that the CNS
      uses only the position error for updating the internal model of the environmental
      dynamics and modifying feedforward commands. Although this strategy is not
      necessarily optimal, it may be the most reliable strategy for iterative
      improvement in performance.

PMID- 16611848
TI  - Hippocampal sharp wave-ripples linked to slow oscillations in rat slow-wave
      sleep.
AB  - Slow oscillations originating in the prefrontal neocortex during slow-wave sleep
      (SWS) group neuronal network activity and thereby presumably support the
      consolidation of memories. Here, we investigated whether the grouping influence
      of slow oscillations extends to hippocampal sharp wave-ripple (SPW) activity
      thought to underlie memory replay processes during SWS. The prefrontal surface
      EEG and multiunit activity (MUA), along with hippocampal local field potentials
      (LFP) from CA1, were recorded in rats during sleep. Average spindle and ripple
      activity and event correlation histograms of SPWs were calculated, time-locked to
      half-waves of slow oscillations. Results confirm decreased prefrontal MUA and
      spindle activity during EEG slow oscillation negativity and increases in this
      activity during subsequent positivity. A remarkably close temporal link was
      revealed between slow oscillations and hippocampal activity, with ripple activity
      and SPWs being also distinctly decreased during negative half-waves and increased
      during slow oscillation positivity. Fine-grained analyses of temporal dynamics
      revealed for the slow oscillation a phase delay of approximately 90 ms with
      reference to up and down states of prefrontal MUA, and of only approximately 60
      ms with reference to changes in SPWs, indicating that up and down states in
      prefrontal MUA precede corresponding changes in hippocampal SPWs by approximately
      30 ms. Results support the notion that the depolarizing surface-positive phase of
      the slow oscillation and the associated up state of prefrontal excitation
      promotes hippocampal SPWs via efferent pathways. The preceding disfacilitation of
      hippocampal events temporally coupled to the negative slow oscillation half-wave
      appears to serve a synchronizing role in this neocorticohippocampal interplay.

PMID- 16611849
TI  - A central pattern generator producing alternative outputs: temporal pattern of
      premotor activity.
AB  - The central pattern generator for heartbeat in medicinal leeches constitutes
      seven identified pairs of segmental heart interneurons. Four identified pairs of
      heart interneurons make a staggered pattern of inhibitory synaptic connections
      with segmental heart motor neurons. Using extracellular recording from multiple
      interneurons in the network in 56 isolated nerve cords, we show that this pattern
      generator produces a side-to-side asymmetric pattern of intersegmental
      coordination among ipsilateral premotor interneurons. This pattern corresponds to
      a similarly asymmetric fictive motor pattern in heart motor neurons and
      asymmetric constriction pattern of the two tubular hearts, synchronous and
      peristaltic. We provide a quantitative description of the firing pattern of all
      the premotor interneurons, including phase, duty cycle, and intraburst frequency
      of this premotor activity pattern. This analysis identifies two stereotypical
      coordination modes corresponding to synchronous and peristaltic, which show phase
      constancy over a broad range of periods as do the fictive motor pattern and the
      heart constriction pattern. Coordination mode is controlled through one segmental
      pair of heart interneurons (switch interneurons). Side-to-side switches in
      coordination mode are a regular feature of this pattern generator and occur with
      changes in activity state of these switch interneurons. Associated with
      synchronous coordination of premotor interneurons, the ipsilateral switch
      interneuron is in an active state, during which it produces rhythmic bursts,
      whereas associated with peristaltic coordination, the ipsilateral switch
      interneuron is largely silent. We argue that timing and pattern elaboration are
      separate functions produced by overlapping subnetworks in the heartbeat central
      pattern generator.

PMID- 16611850
TI  - Metabolism of efavirenz and 8-hydroxyefavirenz by P450 2B6 leads to inactivation
      by two distinct mechanisms.
AB  - Efavirenz is a non-nucleoside human immunodeficiency virus (HIV)-1 reverse
      transcriptase inhibitor used in combination therapy to treat HIV-1. Efavirenz
      metabolism is catalyzed primarily by the polymorphic enzyme P450 2B6. Metabolism
      of efavirenz by P450 2B6 and the naturally occurring P450 2B6.4 mutant led to the
      formation of 8-hydroxyefavirenz. Efavirenz inactivated the 7-ethoxy-4
      (trifluoromethyl)coumarin activity of the wild-type P450 2B6 enzyme in a time-,
      concentration-, and NADPH-dependent manner. However, the P450 2B6.4 variant was
      not inactivated by efavirenz. The ability of efavirenz to inactivate both enzymes
      was investigated using cyclophosphamide and bupropion, two structurally unrelated
      substrates of P450 2B6, as probes. Preincubations with efavirenz decreased the
      ability of the wild-type enzyme to hydroxylate both substrates to similar extents
      but had no effect on the activities of the mutant enzyme. Interestingly, the
      inactivation of the wild-type enzyme was completely reversible after 24 h of
      dialysis as determined by heme, reduced CO spectra, and activity loss. In
      contrast, 8-hydroxyefavirenz, a metabolite of efavirenz, was able to inactivate
      both enzymes irreversibly. These data suggest that incubations of P450 2B6 and
      P450 2B6.4 with either the parent compound efavirenz or the metabolite 8
      hydroxyefavirenz in the reconstituted system result in the formation of two
      different reactive intermediates that lead to losses in enzymatic activity by two
      different mechanisms, one reversible and one irreversible.

PMID- 16611851
TI  - Carcinogen and anticancer drug transport by Mrp2 in vivo: studies using Mrp2
      (Abcc2) knockout mice.
AB  - The ATP-binding-cassette (ABC) transporter multidrug resistance protein (MRP) 2
      (ABCC2) forms a natural barrier and efflux system for various (conjugates of)
      drugs, other xenotoxins, and endogenous compounds. To obtain insight in the
      pharmacological and physiological functions of Mrp2, we generated Mrp2 knockout
      mice, which were viable and fertile but suffered from mild hyperbilirubinemia due
      to impaired excretion of bilirubin monoglucuronides into bile. The mice also had
      an 80-fold decreased biliary glutathione excretion and a 63% reduced bile flow.
      Levels of Mrp3 (Abcc3) in liver and Mrp4 (Abcc4) in kidney of Mrp2-/- mice were
      approximately 2-fold increased. After oral administration of the food-derived
      carcinogens [(14)C]PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and
      [14C]IQ (2-amino-3-methylimidazo[4,5-f]quinoline) plasma values were 1.9- and 1.7
      fold higher in Mrp2-/- mice versus wild-type mice, respectively, demonstrating
      the role of Mrp2 in restricting exposure to these compounds. At a high dose of 50
      mg/kg of the drug [3H]methotrexate, the plasma area under the curve for i.v.
      administration was 1.8-fold higher in Mrp2-/- mice (1345+/-207 versus 734+/-81
      min.microg/ml). No clear plasma concentration difference arose at low dose (1
      mg/kg). Subsequently, Mdr1a/b/Mrp2 knockout mice were generated. Their biliary
      excretion of doxorubicin after i.v. administration (5 mg/kg) was 54-fold
      decreased (0.32+/-0.13 versus 17.30+/-6.59 nmol/g liver in wild type), and a role
      for both Mdr1a/b and Mrp2 in this process was revealed. Our results demonstrate
      that the Mrp2-/- mouse provides a valuable tool for studies of the impact of Mrp2
      on behavior of drugs and other toxins, especially when combined with other ABC
      transporter knockout mice.

PMID- 16611852
TI  - N6-(3-iodobenzyl)-adenosine-5'-N-methylcarboxamide confers cardioprotection at
      reperfusion by inhibiting mitochondrial permeability transition pore opening via
      glycogen synthase kinase 3 beta.
AB  - Although the adenosine A(3) receptor agonist N(6)-(3-iodobenzyl)-adenosine-5'-N
      methylcarboxamide (IB-MECA) has been reported to be cardioprotective at
      reperfusion, little is known about the mechanisms underlying the protection. We
      hypothesized that IB-MECA may protect the heart at reperfusion by preventing the
      opening of mitochondrial permeability transition pore (mPTP) through inactivation
      of glycogen synthase kinase (GSK) 3beta. IB-MECA (1 microM) applied during
      reperfusion reduced infarct size in isolated rat hearts, an effect that was
      abrogated by the selective A3 receptor antagonist 1,4-dihydro-2-methyl-6-phenyl-4
      (phenylethynyl)-3,5-pyridinedicarboxylic acid 3-ethyl-5-[(3-nitrophenyl)
      methyl]ester (MRS1334) (100 nM). The effect of IB-MECA was abrogated by the mPTP
      opener atractyloside (20 microM), implying that the action of IB-MECA may be
      mediated by inhibition of the mPTP opening. In cardiomyocytes, IB-MECA attenuated
      oxidant-induced loss of mitochondrial membrane potential (DeltaPsim), which was
      reversed by MRS1334. IB-MECA also reduced Ca2+-induced mitochondrial swelling. IB
      MECA enhanced phosphorylation of GSK-3beta (Ser9) upon reperfusion, and the GSK-3
      inhibitor 3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione
      (SB216763) (3 microM) mimicked the protective effect of IB-MECA by attenuating
      both infarction and the loss of DeltaPsim. In addition, the effect of IB-MECA on
      GSK-3beta was reversed by wortmannin (100 nM), and IB-MECA was shown to enhance
      Akt phosphorylation upon reperfusion. In contrast, rapamycin (2 nM) failed to
      affect GSK-3beta phosphorylation by IB-MECA, and IB-MECA did not alter
      phosphorylation of either mTOR (Ser2448) or 70s6K (Thr389). Taken together, these
      data suggest that IB-MECA prevents myocardial reperfusion injury by inhibiting
      the mPTP opening through the inactivation of GSK-3beta at reperfusion. IB-MECA
      induced GSK-3beta inhibition is mediated by the PI3-kinase/Akt signal pathway but
      not by the mTOR/p70s6K pathway.

PMID- 16611853
TI  - Pleiotropic effects of the beta-adrenoceptor blocker carvedilol on calcium
      regulation during oxidative stress-induced apoptosis in cardiomyocytes.
AB  - Carvedilol is a nonselective beta-adrenoceptor blocker with multiple pleiotropic
      actions. A recent clinical study suggested that carvedilol may be superior to
      other beta-adrenoceptor blockers in the treatment of heart failure. Despite
      numerous investigations, the underlying mechanisms of carvedilol on improving
      heart failure are yet to be fully established. The purpose of this study is to
      clarify the pleiotropic effect of carvedilol on cytosolic and mitochondrial
      calcium regulation during oxidative stress-induced apoptosis in cardiomyocytes.
      Carvedilol (10 microM), but not metoprolol (10 microM), reduced H2O2 (100 microM)
      induced apoptosis in neonatal rat cardiomyocytes. During the process, changes in
      cytosolic calcium concentration ([Ca2+]i) and mitochondrial calcium concentration
      ([Ca2+]m) and mitochondrial membrane potential (DeltaPsim) were measured by
      fluorescent probes [Fluo-3/acetoxymethyl ester (AM), Rhod-2/AM, and
      tetramethylrhodamine ethyl ester, respectively] and imaged by laser confocal
      microscopy. The results showed that H2O2 caused [Ca2]m overload first, followed
      by [Ca2+]i overload, leading to DeltaPsim dissipation and the induction of
      apoptosis. Carvedilol (10 microM) significantly delayed these processes and
      reduced apoptosis. These effects were not observed with other beta-adrenoceptor
      blockers (metoprolol, atenolol, and propranolol) or with a combination of the
      alpha (phentolamine)- and the beta-adrenoceptor blocker. The antioxidant N-acetyl
      L-cysteine (NAC, 5 mM) and the combination of NAC and propranolol (10 microM)
      showed an effect similar to that of carvedilol. Therefore, the effect of
      carvedilol on H2O2-induced changes in [Ca2+]m, [Ca2+]i, and DeltaPsi(m) is
      independent of alpha- and beta-adrenoceptors but is probably dependent on the
      antioxidant effect.

PMID- 16611854
TI  - Peroxisome proliferator-activated receptor-gamma and retinoic acid X receptor
      alpha represses the TGFbeta1 gene via PTEN-mediated p70 ribosomal S6 kinase-1
      inhibition: role for Zf9 dephosphorylation.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma and retinoic acid X
      receptor (RXR) heterodimer regulates cell growth and differentiation. Zinc finger
      transcription factor-9 (Zf9), whose phosphorylation promotes target genes, is a
      transcription factor essential for transactivation of the transforming growth
      factor (TGF)-beta1 gene. This study investigated whether activation of PPARgamma
      RXR heterodimer inhibits TGFbeta1 gene transcription and Zf9 phosphorylation and,
      if so, what signaling pathway regulates it. Either 15-deoxy-delta(12,14)
      prostaglandin J2 (PGJ2) or 9-cis-retinoic acid (RA) treatment decreased the
      TGFbeta1 mRNA level in L929 fibroblasts. PGJ2 + RA, compared with individual
      treatment alone, synergistically inhibited the TGFbeta1 gene expression, which
      was abrogated by PPARgamma antagonists. Likewise, PGJ2 + RA decreased luciferase
      expression from the TGFbeta1 gene promoter. Promoter deletion analysis of the
      TGFbeta1 gene revealed that pGL3-323 making up to -323-base pair region, but
      lacking PPAR-responsive elements, responded to PGJ2 + RA. PGJ2 + RA treatment
      inhibited the activity of p70 ribosomal S6 kinase-1 (S6K1), abolishing Zf9
      phosphorylation at serine as did rapamycin [a mammalian target of rapamycin
      (mTOR) inhibitor]. Zf9 dephosphorylation by PGJ2 + RA was reversed by
      transfection of cells with the plasmid encoding constitutively active S6K1 (CA
      S6K1). Transfection with dominant negative S6K1 inhibited the TGFbeta1 gene.
      TGFbeta1 gene repression by PGJ2 + RA was consistently antagonized by CA-S6K1.
      Ectopic expression of PPARgamma1 and RXRalpha repressed pGL3-323 transactivation
      with S6K1 inhibition, which was abrogated by CA-S6K1 transfection. PGJ2 + RA
      induced phosphatase and tensin homolog deleted on chromosome 10 (PTEN), whose
      overexpression repressed the TGFbeta1 gene through S6K1 inhibition, decreasing
      extracellular signal-regulated kinase 1/2-90-kDa ribosomal S6 kinase 1 and Akt
      mTOR phosphorylations. Data indicate that activation of PPARgamma-RXR heterodimer
      represses the TGFbeta1 gene and induces Zf9 dephosphorylation via PTEN-mediated
      S6K1 inhibition, providing insight into pharmacological manipulation of the
      TGFbeta1 gene regulation.

PMID- 16611856
TI  - The in vivo and in vitro metabolic profile of 99mTc-NC100668, a new tracer for
      imaging venous thromboembolism: identification and biodistribution of the
      principal radiolabeled metabolite.
AB  - (99m)Tc-NC100668 [Acetyl-Asn-Gln-Glu-Gln-Val-Ser-Pro-Tyr(3-iodo)-Thr-Leu-Leu-Lys
      Gly-NC100194] is a radiopharmaceutical imaging agent being developed to aid the
      diagnosis of thromboembolism. The stability profile of (99m)Tc-NC100668 was
      investigated by high-performance liquid chromatography (HPLC) after in vitro
      exposure to blood and plasma obtained from rat and human, as well as to urine and
      bile obtained from rat. The metabolic profile of (99m)Tc-NC100668 exposed to
      human and rat hepatic S9 (a liver homogenate-rich cytochrome P450) was also
      studied. The profile of (99m)Tc-labeled species in plasma, urine, and bile was
      investigated following i.v. administration of (99m)Tc-NC100668 to rat. The major
      species observed in vitro and in vivo consisted of the (99m)Tc-chelator
      (NC100194) [N,N-Bis(N-(1,1-dimethyl-2-(hydroxylimino
      )propyl)aminoethyl)aminoethylamine] attached to the C-terminal amino acid residue
      and referred to as (99m)Tc-complex of Gly-NC100194. The identity of the major
      metabolite was confirmed by cochromatography with an authentic standard and the
      genuine metabolite using a second HPLC method. The minor metabolites were sodium
      pertechnetate ((99m)Tc) and (99m)Tc-NC100194. In addition, a small number of
      other species were transiently observed in vitro; they were not investigated
      further. The biodistribution of the major metabolite was studied in male Wistar
      rats. The affinity of the major metabolite toward plasma clot was established
      using a plasma clot-forming assay. A minor uptake of (99m)Tc-complex of Gly
      NC100194 in the plasma clot and a rapid removal from the body were noted. In
      conclusion, the metabolites of (99m)Tc-NC100668 are not anticipated to have a
      negative impact on the ability of the test substance to image blood clots.

PMID- 16611855
TI  - Interleukin-2 suppression by 2-arachidonyl glycerol is mediated through
      peroxisome proliferator-activated receptor gamma independently of cannabinoid
      receptors 1 and 2.
AB  - 2-Arachidonyl glycerol (2-AG) is an endogenous arachidonic acid derivative that
      binds cannabinoid receptors CB1 and CB2 and is hence termed an endocannabinoid. 2
      AG also modulates a variety of immunological responses, including expression of
      the autocrine/paracrine T cell growth factor interleukin (IL)-2. The objective of
      the present studies was to determine the mechanism responsible for IL-2
      suppression by 2-AG. Because of the labile properties of 2-AG, 2-AG ether, a
      nonhydrolyzable analog of 2-AG, was also used. Both 2-AG and 2-AG ether
      suppressed IL-2 expression independently of CB1 and CB2, as demonstrated in
      leukocytes derived from CB1/CB2-null mice. Moreover, we demonstrated that both 2
      AG and 2-AG ether treatment activated peroxisome proliferator-activated receptor
      gamma (PPARgamma), as evidenced by forced differentiation of 3T3-L1 cells into
      adipocytes, induction of aP2 mRNA levels, and activation of a PPARgamma-specific
      luciferase reporter in transiently transfected 3T3-L1 cells. Consequently, the
      putative role of PPARgamma in IL-2 suppression by 2-AG and 2-AG ether was
      examined in Jurkat T cells. Concordant with PPARgamma involvement, the PPARgamma
      specific antagonist 2-chloro-5-nitro-N-(4-pyridyl)-benzamide (T0070907) blocked 2
      AG- and 2-AG ether-mediated IL-2 suppression. Likewise, 2-AG suppressed the
      transcriptional activity of two transcription factors crucial for IL-2
      expression, nuclear factor of activated T cells and nuclear factor kappaB, in the
      absence but not in the presence of T0070907. 2-AG treatment also induced
      PPARgamma binding to a PPAR response element in activated Jurkat T cells.
      Together, the aforementioned studies identify PPARgamma as a novel intracellular
      target of 2-AG, which mediates the suppression of IL-2 by 2-AG in a manner that
      is independent of CB1 and/or CB2.

PMID- 16611857
TI  - Predominant contribution of OATP1B3 to the hepatic uptake of telmisartan, an
      angiotensin II receptor antagonist, in humans.
AB  - Telmisartan, a nonpeptide angiotensin II receptor antagonist, is selectively
      distributed to liver. In the present study, we have characterized the
      contribution of organic anion transporting polypeptide (OATP) isoforms to the
      hepatic uptake of telmisartan by isolated rat hepatocytes, human cryopreserved
      hepatocytes, and human transporter-expressing cells. Because it is difficult to
      evaluate the transport activity of telmisartan because of its extensive
      adsorption to cells and culture materials, we performed the uptake study in the
      presence of human serum albumin. The saturable uptake of telmisartan into
      isolated rat hepatocytes took place in a Na(+)-independent manner and was
      inhibited by pravastatin, taurocholate, and digoxin, which are Oatp substrates
      and inhibitors, but not by organic cation, tetraethylammonium, indicating the
      involvement of Oatp isoforms in its uptake into rat hepatocytes. To identify
      which human OATP transporters are important for the hepatic uptake of
      telmisartan, the uptake assay was carried out using OATP1B1- and OATP1B3
      expressing human embryonic kidney 293 cells and cryopreserved human hepatocytes.
      The uptake of telmisartan by OATP1B3-expressing cells was saturable (K(m) = 0.81
      microM) and significantly higher than that by vector-transfected cells. In
      contrast, no significant uptake was observed in OATP1B1-expressing cells. We also
      observed the saturable uptake of telmisartan by human hepatocytes. Thirty
      micromolar estrone-3-sulfate, which can selectively inhibit OATP1B1-mediated
      uptake compared with OATP1B3, did not inhibit the uptake of telmisartan in human
      hepatocytes, whereas it could inhibit the uptake of estradiol 17beta-d
      glucuronide mediated by OATP1B1. These results suggest that OATP1B3 is
      predominantly involved in the hepatic uptake of telmisartan in humans.

PMID- 16611858
TI  - Profiling the hepatic effects of flutamide in rats: a microarray comparison with
      classical aryl hydrocarbon receptor ligands and atypical CYP1A inducers.
AB  - The antiandrogen flutamide (FLU) is used primarily for prostate cancer and is an
      idiosyncratic hepatotoxicant that sometimes causes severe liver problems. To
      investigate FLU's overt hepatic effects, especially on inducible drug clearance
      related gene networks, FLU's hepatic gene expression profile was examined in
      female Sprague-Dawley rats using approximately 22,500 oligonucleotide
      microarrays. Rats were dosed daily for 3 days with FLU at 500, 250, 62.5, 31.3,
      and 15.6 mg/kg/day, and hepatic RNA was isolated. FLU resulted in the dose
      dependent regulation of approximately 350 genes. Employing a gene-response
      compendium, FLU was compared with three classical aryl hydrocarbon receptor (AhR)
      ligands, 3-methylcholanthrene, benzo[a]pyrene, and beta-naphthoflavone, and four
      atypical CYP1A inducers, indole-3-carbinol (I3C), omeprazole (OME),
      chlorpromazine (CPZ), and clotrimazole (CLO). The FLU gene response was
      comparable with classical AhR ligands across a signature AhR ligand gene set that
      included CYP1A1 and other members of the AhR gene battery. Dose-related responses
      of CYP1 genes established a maximum response ceiling and discerned potency
      differences in atypical inducers. FLU had a sharp down-regulation of c-fos that
      was comparable with all the compounds except CPZ and CLO. FLU absorption,
      distribution, metabolism, and excretion (ADME) gene expression analysis revealed
      that FLU, as well as I3C and OME, induced CYP2B and CYP3A, distinguishing them
      from the classical AhR ligands. By using a compendium of gene expression
      profiles, FLU was shown to signal in rats similar to an AhR activator with
      additional CYP2B and CYP3A effects that most resembled the ADME gene expression
      pattern of the atypical CYP1A inducers I3C and OME.

PMID- 16611859
TI  - Stochastic prediction of CYP3A-mediated inhibition of midazolam clearance by
      ketoconazole.
AB  - Conventional methods to forecast CYP3A-mediated drug-drug interactions have not
      employed stochastic approaches that integrate pharmacokinetic (PK) variability
      and relevant covariates to predict inhibition in terms of probability and
      uncertainty. Empirical approaches to predict the extent of inhibition may not
      account for nonlinear or non-steady-state conditions, such as first-pass effects
      or accumulation of inhibitor concentration with multiple dosing. A
      physiologically based PK model was developed to predict the inhibition of CYP3A
      by ketoconazole (KTZ), using midazolam (MDZ) as the substrate. The model
      integrated PK models of MDZ and KTZ, in vitro inhibition kinetics of KTZ, and the
      variability and uncertainty associated with these parameters. This model
      predicted the time- and dose-dependent inhibitory effect of KTZ on MDZ oral
      clearance. The predictive performance of the model was validated using the
      results of five published KTZ-MDZ studies. The model improves the accuracy of
      predicting the inhibitory effect of increasing KTZ dosing on MDZ PK by
      incorporating a saturable KTZ efflux from the site of enzyme inhibition in the
      liver. The results of simulations using the model supported the KTZ dose of 400
      mg once daily as the optimal regimen to achieve maximum inhibition by KTZ.
      Sensitivity analyses revealed that the most influential variable on the
      prediction of inhibition was the fractional clearance of MDZ mediated by CYP3A.
      The model may be used prospectively to improve the quantitative prediction of
      CYP3A inhibition and aid the optimization of study designs for CYP3A-mediated
      drug-drug interaction studies in drug development.

PMID- 16611860
TI  - Quantitative determination of aristolochic acid-derived DNA adducts in rats using
      32P-postlabeling/polyacrylamide gel electrophoresis analysis.
AB  - Aristolochic acids (AA) are nephrotoxic and carcinogenic nitroaromatic compounds
      produced by the Aristolochiaceae family of plants. Ingestion of these phytotoxins
      by humans results in a syndrome known as AA nephropathy, characterized by renal
      tubulointerstitial fibrosis and upper urothelial cancer. After activation by
      cellular enzymes, AA I and II react with DNA to form covalent adducts and as such
      represent potential biomarkers for studies of AA toxicity. Using site
      specifically modified oligodeoxynucleotides as standards, we have developed a
      method for quantifying 7-(deoxyadenosin-N(6)-yl) aristolactam-DNA or 7
      (deoxyguanosin-N(2)-yl) aristolactam-DNA adducts in tissues of Wistar rats using
      an assay in which (32)P-postlabeling techniques are coupled with nondenaturing
      polyacrylamide gel electrophoresis. The limit of detection with this technique is
      five adducts in 10(9) nucleotides for a 5-microg DNA sample. In contrast to
      previous reports, we find that the levels of AA adducts in renal tissues of
      Wistar rats treated p.o. with AA for 1 week with 5 mg/kg/day of AA I or AA II
      were much higher than that in the forestomach. Highest adduct levels were
      observed in rats treated with AA II, suggesting that this compound may be more
      genotoxic than AA I. Treatment of rats with aristolactam I, an end-product of AA
      I metabolism, resulted in a much lower level of adduction. This study establishes
      the feasibility of using AA-DNA adducts as intermediate biomarkers of exposure in
      studies of AA nephropathy and its associated urothelial cancer.

PMID- 16611862
TI  - Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and
      fatty acid amide hydrolase activity in male germ cells.
AB  - N-arachidonoylethanolamide (anandamide [AEA]) is the main endocannabinoid
      described to date in the testis. It exerts its effects through the activation of
      G-protein coupled cannabinoid receptors (CNR). However, the activity of AEA in
      controlling male reproduction is still poorly known. Here we provide direct
      evidence on the presence of the "endocannabinoid system," constituted by type-1
      cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH), in the frog
      Rana esculenta testis demonstrating its expression in tubular compartment. In
      fact, during the annual reproductive cycle, both proteins increase in September,
      when the appearance of spermatids (SPT) occurs. Immunocytochemistry confirms
      their localization in germ cells and, in particular, in elongated SPT. Signals
      are still present in spermatozoa (SPZ), as demonstrated by Western blot analysis.
      Furthermore, the activation of CNR1 reduces sperm motility. Comparative research,
      carried out using mouse and rat SPZ, definitely indicates that the
      endocannabinoid system operates in SPZ of phylogenetically distant species. A
      conserved physiological role of endocannabinoid system in controlling the
      inhibition of sperm motility is suggested.

PMID- 16611861
TI  - Identification of human hepatic cytochrome P450 enzymes involved in the
      metabolism of 8-prenylnaringenin and isoxanthohumol from hops (Humulus lupulus
      L.).
AB  - The female flowers of hops (Humulus lupulus L.) are used in the brewing of beer
      and are under investigation for use in dietary supplements for the management of
      menopausal symptoms in women. Hop extracts contain the weakly estrogenic compound
      isoxanthohumol (IX), proestrogenic xanthohumol, and the potent estrogen 8
      prenylnaringenin (8PN). Because IX can be metabolized in the human liver to form
      8PN, the specific cytochrome P450 (P450) enzymes responsible for this O
      demethylation reaction were identified. In addition, the enzymes that convert IX
      and 8PN to their most abundant metabolites were identified because these
      metabolic pathways might also affect the estrogenicity of hop preparations.
      Specifically, the P450 enzymes that catalyze the oxidation of the prenyl side
      chains of IX and 8PN into trans- or cis-alcohols were investigated. Human liver
      microsomes and monoclonal antibodies that inhibit specific P450 enzymes were used
      in combination with liquid chromatography/mass spectrometry to identify the
      enzymes responsible for these transformations. CYP2C19 was found to catalyze the
      formation of both cis- and trans-alcohols of the prenyl side chain of 8PN with
      K(m) values of 14.8 +/- 3.2 and 16.6 +/- 4.6 microM, respectively. CYP2C8
      converted 8PN regioselectively to the trans-alcohol of the prenyl group with a
      K(m) of 3.7 +/- 0.9 microM. Finally, CYP1A2 was found to catalyze the O
      demethylation of IX to generate 8PN, with a K(m) value of 17.8 +/- 3.7 microM.
      These results suggest that the estrogenicity of hop constituents in vivo will
      depend in part on metabolic conversion that may show individual variation.

PMID- 16611863
TI  - Dynamic HIF1A regulation during human placental development.
AB  - The human placenta is a unique organ in terms of oxygenation as it undergoes a
      transition from a low to a more oxygenated environment. This physiological switch
      in oxygen tension is a prerequisite for proper placental development and involves
      the hypoxia inducible factor (HIF). HIF is stable and initiates gene
      transcription under hypoxia, whereas in normoxia, interaction with the von Hippel
      Lindau tumor suppressor protein (VHL) leads to rapid degradation of the HIF1A
      subunit. The degradation requires formation of a multiprotein complex (VHLCBC)
      and hydroxylation of HIF1A proline residues via members of the egg-laying
      defective nine (EGLN) family. Herein, we have investigated the regulatory
      mechanisms of HIF1A expression during human placental development. Expression of
      HIF1A and VHL was high at 7-9 wk of gestation, when oxygen tension is low, and
      decreased when placental oxygen tension increases (10-12 wk of gestation). During
      early placentation, HIF1A localized in cytotrophoblasts, while VHL was present in
      syncytiotrophoblasts. At 10-12 wk, VHL appeared in cytotrophoblast cells, which
      coincided with the disappearance of HIF1A. At the same time the association of
      VHL and Cullin 2 as well as ubiquitination of HIF1A was maximal. EGLN1, EGLN2,
      and EGLN3 were also temporally expressed in an oxygen-dependent fashion, with
      greatest mRNA expression at 10-12 wk of gestation. Inhibition of EGLN activity
      increased HIF1A stability in villous explants and stimulated transforming growth
      factor beta 3 (TGFB3) expression consistent with promoter analyses showing that
      HIF1A transactivates TGFB3. These data demonstrate that during placental
      development, HIF1A is regulated by temporal and spatial changes in expression and
      association of molecules forming the multi-protein VHLCBC complex as well as
      prolyl hydroxylase activities.

PMID- 16611864
TI  - Cigarette smoking and the risk of systemic lupus erythematosus and rheumatoid
      arthritis.

PMID- 16611865
TI  - Morphological and quantitative assessment of mast cells in rheumatoid arthritis
      associated non-specific interstitial pneumonia and usual interstitial pneumonia.
AB  - BACKGROUND: The role of mast cells in extra-articular manifestations of
      rheumatoid arthritis (RA) has not been studied so far. OBJECTIVE: To characterise
      and quantify mast cells in RA associated interstitial pneumonia (IP) by an
      immunohistological study. METHODS: Lung biopsy specimens from 15 patients with RA
      associated IP, 12 patients with idiopathic IP, and 5 control patients were
      stained with antibodies directed against tryptase (mast cell marker).
      Morphological characterisation of stained specimens was carried out and staining
      was quantified by computer assisted image analysis. RESULTS: Tryptase staining
      showed the marked presence of mast cells in idiopathic IP and in RA associated
      IP. A significant difference in stained tissue area was found between RA
      associated IP (2.6%, IQR 2.0-3.2%, p = 0.015) and idiopathic IP (3.1%, IQR 1.8
      3.7%, p = 0.003) compared with control tissue specimens (1.0%, IQR 0.7-1.5%). The
      extent of mast cell infiltration correlated well and inversely with pulmonary
      function variables. CONCLUSIONS: Mast cell infiltrates are present in RA
      associated IP and idiopathic IP. The observed correlation of pulmonary function
      and mast cell numbers would be consistent with the proposed role of mast cell
      mediators in the promotion of fibrogenesis. The findings provide a rationale for
      studying functional aspects of mast cell involvement in the pathogenesis of RA
      associated lung disease.

PMID- 16611866
TI  - Hypertrophic osteoarthropathy associated with gastrointestinal stromal tumour.

PMID- 16611867
TI  - Prevalence of an abnormal ankle-brachial index in patients with antiphospholipid
      syndrome with pregnancy loss but without thrombosis: a controlled study.

PMID- 16611868
TI  - Pulmonary nodules as initial manifestation of primary Sjogren's syndrome.

PMID- 16611869
TI  - Treatment of ankylosing spondylitis with pamidronate: an open label study.

PMID- 16611870
TI  - Glucocorticoid resistance in a girl with Takayasu's arteritis.

PMID- 16611871
TI  - Successful treatment of meningeal involvement in Wegener's granulomatosis with
      infliximab.

PMID- 16611872
TI  - Bosentan may induce arthritis flare in patients with scleroderma concomitantly
      treated with methotrexate.

PMID- 16611873
TI  - Orthopaedic surgery in patients with rheumatoid arthritis: a shift towards more
      frequent and earlier non-joint-sacrificing surgery.

PMID- 16611874
TI  - Amelioration of severe psoriasis with psoriatic arthritis for 20 years after
      allogeneic haematopoietic stem cell transplantation.

PMID- 16611875
TI  - An unusual cause of death in Wegener's granulomatosis.

PMID- 16611876
TI  - Does anti-tumour necrosis factor alpha treatment modify the tuberculin PPD
      response?

PMID- 16611878
TI  - Short term palindromic rheumatism after clopidogrel use.

PMID- 16611879
TI  - Cognitive function and symptoms in adolescents with schizotypal personality
      disorder.
AB  - Cognitive deficits have been documented in schizophrenia and spectrum disorders.
      This study examines cognitive functioning and its relation to symptoms in
      adolescents with schizotypal personality disorder (SPD). Participants are 89
      adolescents recruited for a study of youth at risk for Axis I disorders,
      especially psychosis. At intake, 34 met criteria for SPD, 38 for another Axis II
      disorder and/or conduct disorder (Other disorder-OD), and 17 did not currently
      meet criteria for any DSM-IV disorder (normal control-NC). At initial assessment,
      cognitive functioning was measured using subtests from the Wechsler Intelligence
      Scales and Wechsler Memory Scales (WMS), and symptoms were measured using the
      Structured Interview for Prodromal Symptoms (SIPS). At the time of this report,
      50 were readministered the SIPS at 1-year follow-up (T2). The SPD group scored
      significantly below the NC group on the Arithmetic subtest of the Wechsler
      Intelligence Scales, but there was only limited evidence of group differences on
      the WMS. Poorer performance on the Wechsler Intelligence Scales was associated
      with greater severity of negative and disorganized symptoms. Deficits on the WMS
      were linked with more severe disorganized symptoms. The findings reported here
      are consistent with previous reports of limited cognitive deficits in adolescents
      with SPD, with the most marked deficits in mental arithmetic. The associations
      between symptoms and cognitive scores parallel those observed in adults with
      schizophrenia and spectrum disorder, and they are consistent with the notion that
      negative symptoms are more stable and partially reflect premorbid cognitive
      functions.

PMID- 16611880
TI  - Animal origins of the severe acute respiratory syndrome coronavirus: insight from
      ACE2-S-protein interactions.

PMID- 16611881
TI  - Investigating the origin and spread of hepatitis C virus genotype 5a.
AB  - Epidemiological and phylogenetic studies of hepatitis C virus (HCV) have
      identified six major HCV genotypes and have attempted to characterize their
      origin and spread worldwide. Putative regions of endemic infection have been
      identified for all HCV genotypes except HCV genotype 5a. Although HCV genotype 5a
      was previously thought to be largely restricted to the northern part of South
      Africa, this study reports an unexpected cluster of the genotype in West Flanders
      Province in Belgium. To investigate the molecular epidemiology of this cluster
      and of HCV genotype 5a in general, a rigorous phylogenetic analysis of Belgian
      and South African HCV genotype 5a samples was performed. Remarkably, the Belgian
      and South African strains form two distinct clusters of similar diversity. We
      used a Bayesian coalescent method to estimate the rate of virus spread through
      time for HCV genotype 5a in both regions. Our results indicate that HCV genotype
      5a strains have been spreading independently in Belgium and South Africa for more
      than 100 years, with a rate of spread characteristic of an epidemic genotype.
      These findings have major implications for tracing the origin of HCV genotype 5a.
      Here, we speculate about the possible origins of these clusters.

PMID- 16611882
TI  - An alternative splice product of IkappaB kinase (IKKgamma), IKKgamma-delta,
      differentially mediates cytokine and human T-cell leukemia virus type 1 tax
      induced NF-kappaB activation.
AB  - NF-kappaB is an inducible transcription factor mediating innate immune responses
      whose activity is controlled by the multiprotein IkappaB kinase (IKK)
      "signalsome". The core IKK consists of two catalytic serine kinases, IKKalpha and
      IKKbeta, and a noncatalytic subunit, IKKgamma. IKKgamma is required for IKK
      activity by mediating kinase oligomerization and serving to couple the core
      catalytic subunits to upstream mitogen-activated protein 3-kinase cascades. We
      have discovered an alternatively spliced IKKgamma mRNA isoform, encoding an in
      frame deletion of exon 5, termed IKKgamma-delta. Using a specific reverse
      transcription-PCR assay, we find that IKKgamma-delta is widely expressed in
      cultured human cells and normal human tissues. Because IKKgamma-Delta protein is
      lacking a critical coiled-coil domain important in protein-protein interactions,
      we sought to determine its signaling properties by examining its ability to self
      associate, couple to activators of the canonical pathway, and mediate human T
      cell leukemia virus type 1 (HTLV-1) Tax-induced NF-kappaB activity.
      Coimmunoprecipitation and confocal colocalization assays indicate IKKgamma-delta
      has strong homo- and heterotypic association with wild-type (WT) IKKgamma and,
      like IKKgamma WT, associates with the IKKbeta kinase. Similarly, IKKgamma-delta
      mediates IKK kinase activity and downstream NF-kappaB-dependent transcription in
      response to tumor necrosis factor (TNF) and the NF-kappaB-inducing kinase
      IKKalpha signaling pathway. Surprisingly, however, in contrast to IKKgamma WT,
      IKKgamma-delta is not able to mediate HTLV-1 Tax-induced NF-kappaB-dependent
      transcription, even though IKKgamma-delta binds and colocalizes with Tax. These
      observations suggest that IKKgamma-delta is a functionally distinct alternatively
      spliced mRNA product differentially mediating TNF-induced, but not Tax-induced,
      signals converging on the IKK signalsome. Differing levels of IKKgamma-delta
      expression, therefore, may affect signal transduction cascades coupling to IKK.

PMID- 16611883
TI  - Generation of measles virus with a segmented RNA genome.
AB  - Viruses classified in the order Mononegavirales have a single nonsegmented RNA
      molecule as the genome and employ similar strategies for genome replication and
      gene expression. Infectious particles of Measles virus (MeV), a member of the
      family Paramyxoviridae in the order Mononegavirales, with two or three RNA genome
      segments (2 seg- or 3 seg-MeV) were generated using a highly efficient reverse
      genetics system. All RNA segments of the viruses were designed to have authentic
      3' and 5' self-complementary termini, similar to those of negative-stranded RNA
      viruses that intrinsically have multiple RNA genome segments. The 2 seg- and 3
      seg-MeV were viable and replicated well in cultured cells. 3 seg-MeV could
      accommodate up to six additional transcriptional units, five of which were shown
      to be capable of expressing foreign proteins efficiently. These data indicate
      that the MeV genome can be segmented, providing an experimental insight into the
      divergence of the negative-stranded RNA viruses with nonsegmented or segmented
      RNA genomes. They also illustrate a new strategy to develop mononegavirus-derived
      vectors harboring multiple additional transcriptional units.

PMID- 16611884
TI  - The E7 oncoprotein is translated from spliced E6*I transcripts in high-risk human
      papillomavirus type 16- or type 18-positive cervical cancer cell lines via
      translation reinitiation.
AB  - High-risk human papillomaviruses (HPVs) encode two viral oncoproteins, E6 and E7,
      from a single bicistronic pre-mRNA containing three exons and two introns.
      Retention of intron 1 in the E6 coding region is essential for production of the
      full-length E6 oncoprotein. However, splicing of intron 1 is extremely efficient
      in cervical cancer cells, leading to the production of a spliced transcript,
      E6*I, of E6. Here, we investigated whether this splicing of intron 1 might
      benefit E7 production. Using RNA interference as a tool, we targeted the intron 1
      region using small interfering RNAs (siRNAs) in HPV-positive cell lines. At an
      effective low dose, the siRNAs specifically suppressed E6 expression but not E7
      expression, as demonstrated by the stabilization of p53. However, at high doses
      the HPV18 intron 1-specific siRNA substantially and specifically reduced the
      level of the 18E6*I mRNA lacking the intron region in HeLa cells, implying its
      nuclear silencing on the pre-mRNA before RNA splicing. Two other siRNAs targeting
      the exon 2 regions of HPV16 and -18, which encode the E7 oncoprotein, reduced the
      E6*I mRNAs to a remarkable extent and preferentially suppressed expression of E7,
      leading to accumulation of hypophosphorylated p105Rb and cell cycle arrest,
      indicating that the majority of E7 proteins are the translational products of
      E6*I mRNAs. This was confirmed by transient transfection in 293 cells: E7 could
      be translated only from the E7 open reading frame (ORF) on E6*I mRNA in a
      distance-dependent matter of upstream E6*I ORF by translation reinitiation. The
      data thus provide direct evidence that the E6*I mRNAs of high-risk HPVs are
      responsible for E7 production.

PMID- 16611885
TI  - Reconstitution of herpes simplex virus microtubule-dependent trafficking in
      vitro.
AB  - Microtubule-mediated anterograde transport of herpes simplex virus (HSV) from the
      neuronal cell body to the axon terminal is crucial for the spread and
      transmission of the virus. It is therefore of central importance to identify the
      cellular and viral factors responsible for this trafficking event. In previous
      studies, we isolated HSV-containing cytoplasmic organelles from infected cells
      and showed that they represent the first and only destination for HSV capsids
      after they emerge from the nucleus. In the present study, we tested whether these
      cytoplasmic compartments were capable of microtubule-dependent traffic.
      Organelles containing green fluorescent protein-labeled HSV capsids were isolated
      and found to be able to bind rhodamine-labeled microtubules polymerized in vitro.
      Following the addition of ATP, the HSV-associated organelles trafficked along the
      microtubules, as visualized by time lapse microscopy in an imaging microchamber.
      The velocity and processivity of trafficking resembled those seen for neurotropic
      herpesvirus traffic in living axons. The use of motor-specific inhibitors
      indicated that traffic was predominantly kinesin mediated, consistent with the
      reconstitution of anterograde traffic. Immunocytochemical studies revealed that
      the majority of HSV-containing organelles attached to the microtubules contained
      the trans-Golgi network marker TGN46. This simple, minimal reconstitution of
      microtubule-mediated anterograde traffic should facilitate and complement
      molecular analysis of HSV egress in vivo.

PMID- 16611886
TI  - Bromodomain protein 4 mediates the papillomavirus E2 transcriptional activation
      function.
AB  - The papillomavirus E2 regulatory protein has essential roles in viral
      transcription and the initiation of viral DNA replication as well as for viral
      genome maintenance. Brd4 has recently been identified as a major E2-interacting
      protein and, in the case of the bovine papillomavirus type 1, serves to tether E2
      and the viral genomes to mitotic chromosomes in dividing cells, thus ensuring
      viral genome maintenance. We have explored the possibility that Brd4 is involved
      in other E2 functions. By analyzing the binding of Brd4 to a series of alanine
      scanning substitution mutants of the human papillomavirus type 16 E2 N-terminal
      transactivation domain, we found that amino acids required for Brd4 binding were
      also required for transcriptional activation but not for viral DNA replication.
      Functional studies of cells expressing either the C-terminal domain of Brd4 that
      can bind E2 and compete its binding to Brd4 or short interfering RNA to knock
      down Brd4 protein levels revealed a role for Brd4 in the transcriptional
      activation function of E2 but not for its viral DNA replication function.
      Therefore, these studies establish a broader role for Brd4 in the papillomavirus
      life cycle than as the chromosome tether for E2 during mitosis.

PMID- 16611887
TI  - Role for TLR2 in NK cell-mediated control of murine cytomegalovirus in vivo.
AB  - Natural killer (NK) cells are essential for the early control of murine
      cytomegalovirus (MCMV) infection. Here, we demonstrate that toll-like receptor 2
      (TLR2) plays a role in the NK cell-mediated control of MCMV. TLR2 knockout (KO)
      mice had elevated levels of MCMV in the spleen and liver on day 4 postinfection
      compared to C57BL/6 mice. In vivo depletion of NK cells with anti-NK1.1
      antibodies, however, eliminated the differences in viral titers between the two
      groups, suggesting that the effect of TLR2 on MCMV clearance on day 4 was NK cell
      mediated. The defect in early antiviral control was associated with a decreased
      NK cell population in the spleen and liver and reduced amounts of interleukin-18
      and alpha/beta interferon secreted in the TLR2 KO mice. Our studies suggest that
      in addition to the reported involvement of TLR9 and TLR3, TLR2 is also involved
      in innate immune responses to MCMV infection.

PMID- 16611888
TI  - Targeting of p300/CREB binding protein coactivators by simian virus 40 is
      mediated through p53.
AB  - The primary transforming functions of simian virus 40 large T antigen (SV40 LT)
      are conferred primarily through the binding and inactivation of p53 and the
      retinoblastoma family members. Normal p53 function requires an association with
      the CREB binding protein (CBP)/p300 coactivators, and a ternary complex
      containing SV40 LT, p53, and CBP/p300 has been identified previously. In this
      report, we have evaluated a secondary function of p53 bound to the SV40 LT
      complex in mediating the binding of human CBP/p300. We demonstrate that p53
      associated with SV40 LT was posttranslationally modified in a manner consistent
      with the binding of CBP/p300. Furthermore, expression of SV40 LT induced the
      proportion of p53 phosphorylated on S15. An essential function for p53 in
      bridging the interaction between SV40 LT and CBP/p300 was identified through the
      reconstitution of the SV40 LT-CBP/p300 complex upon p53 reexpression in p53-null
      cells. In addition, the SV40 LT-CBP/p300 complex was disrupted through RNA
      interference-mediated depletion of endogenous p53. We also demonstrate that SV40
      LT was acetylated in a p300- and p53-dependent manner, at least in part through
      the CH3 domain of p300. Therefore, the binding of p53 serves to modify SV40 LT by
      targeting CBP and p300 binding to direct the acetylation of SV40 LT.

PMID- 16611889
TI  - Crystal structure of the simian virus 40 large T-antigen origin-binding domain.
AB  - The origins of replication of DNA tumor viruses have a highly conserved feature,
      namely, multiple binding sites for their respective initiator proteins arranged
      as inverted repeats. In the 1.45-angstroms crystal structure of the simian virus
      40 large T-antigen (T-ag) origin-binding domain (obd) reported herein, T-ag obd
      monomers form a left-handed spiral with an inner channel of 30 angstroms having
      six monomers per turn. The inner surface of the spiral is positively charged and
      includes residues known to bind DNA. Residues implicated in hexamerization of
      full-length T-ag are located at the interface between adjacent T-ag obd monomers.
      These data provide a high-resolution model of the hexamer of origin-binding
      domains observed in electron microscopy studies and allow the obd's to be
      oriented relative to the hexamer of T-ag helicase domains to which they are
      connected.

PMID- 16611890
TI  - Role of the alpha/beta interferon response in the acquisition of susceptibility
      to poliovirus by kidney cells in culture.
AB  - Replication of poliovirus (PV) is restricted to a few sites, including the brain
      and spinal cord. However, this neurotropism is not conserved in cultured cells.
      Monkey kidney cells become susceptible to PV infection after cultivation in
      vitro, and cell lines of monolayer cultures from almost any tissue of primates
      are susceptible to PV infection. These observations suggest that cellular changes
      during cultivation are required for acquisition of susceptibility. The molecular
      basis for the cellular changes during this process is not known. We investigated
      the relationship between PV susceptibility and interferon (IFN) response in
      primary cultured kidney and liver cells derived from transgenic mice expressing
      human PV receptor and in several primate cell lines. Both kidneys and liver in
      vivo showed rapid IFN response within 6 h postinfection. However, monkey and
      mouse kidney cells in culture and primate cell lines, which were susceptible to
      PV, did not show such rapid response or showed no response at all. On the other
      hand, primary cultured liver cells, which were partially resistant to infection,
      showed rapid IFN induction. The loss of IFN inducibility in kidney cells was
      associated with a decrease in expression of IFN-stimulated genes involved in IFN
      response. Mouse kidney cells pretreated with a small dose of IFN, in turn,
      restored IFN inducibility and resistance to PV. These results strongly suggest
      that the cells in culture acquire PV susceptibility during the process of
      cultivation by losing rapid IFN response that has been normally maintained in
      extraneural tissues in vivo.

PMID- 16611891
TI  - Enhanced replication of simian immunodeficiency virus adjacent to
      catecholaminergic varicosities in primate lymph nodes.
AB  - Clinical and in vitro studies have shown that activity of the autonomic nervous
      system (ANS) can stimulate lentivirus replication. To define the potential
      anatomical basis for this effect, we analyzed the spatial relationship between
      catecholaminergic neural fibers and sites of simian immunodeficiency virus (SIV)
      replication in lymph nodes from rhesus macaques experimentally infected with
      SIVmac251. Viral replication was mapped by in situ hybridization for SIV env,
      gag, and nef RNA, and catecholaminergic varicosities from the ANS were mapped by
      sucrose phosphate glyoxylic acid chemofluorescence. Spatial statistical analyses
      showed that the likelihood of active SIV replication increased by 3.9-fold in the
      vicinity of catecholaminergic varicosities (P < 0.0001). The densities of both
      ANS innervation and SIV replication differed across cortical, paracortical, and
      medullary regions of the lymph node, but analyses of each region separately
      continued to show increased replication of SIV adjacent to catecholaminergic
      varicosities. Ancillary analyses ruled out the possibility that SIV-induced
      alterations in lymph node architecture might create a spurious spatial
      association. These data support human clinical studies and in vitro molecular
      analyses showing that catecholamine neurotransmitters from the ANS can increase
      lentiviral replication by identifying a specific anatomic context for
      interactions between ANS neural fibers and replication of SIV in lymphoid tissue.

PMID- 16611892
TI  - Repair and polyadenylation of a naturally occurring hepatitis C virus 3'
      nontranslated region-shorter variant in selectable replicon cell lines.
AB  - The 3' nontranslated region (NTR) of the hepatitis C virus (HCV) genome is highly
      conserved and contains specific cis-acting RNA motifs that are essential in
      directing the viral replication machinery to initiate at the correct 3' end of
      the viral genome. Since the ends of viral genomes may be damaged by cellular
      RNases, preventing the initiation of viral RNA replication, stable RNA hairpin
      structures in the 3' NTR may also be essential in host defense against
      exoribonucleases. During 3'-terminal sequence analysis of serum samples of a
      patient with chronic hepatitis related to an HCV1b infection, a number of clones
      were obtained that were several nucleotides shorter at the extreme 3' end of the
      genome. These shorter 3' ends were engineered in selectable HCV replicons in
      order to enable the study of RNA replication in cell culture. When in vitro
      transcribed subgenomic RNAs, containing shorter 3' ends, were introduced into Huh
      7 cells, a few selectable colonies were obtained, and the 3' terminus of these
      subgenomic RNAs was sequenced. Interestingly, most genomes recovered from these
      colonies had regained the wild-type 3' ends, showing that HCV, like several other
      positive-stranded RNA viruses, has developed a strategy to repair deleted 3' end
      nucleotides. Furthermore, we found several genomes in these replicon colonies
      that contained a poly(A) tail and a short linker sequence preceding the poly(A)
      tail. After recloning and subsequent passage in Huh-7 cells, these poly(A) tails
      persisted and varied in length. In addition, the connecting linker became highly
      diverse in sequence and length, suggesting that these tails are actively
      replicated. The possible terminal repair mechanisms, including roles for the
      poly(A) tail addition, are discussed.

PMID- 16611893
TI  - Identification of functionally important negatively charged residues in the
      carboxy end of mouse hepatitis coronavirus A59 nucleocapsid protein.
AB  - The coronavirus nucleocapsid (N) protein is a multifunctional viral gene product
      that encapsidates the RNA genome and also plays some as yet not fully defined
      role in viral RNA replication and/or transcription. A number of conserved
      negatively charged amino acids are located within domain III in the carboxy end
      of all coronavirus N proteins. Previous studies suggested that the negatively
      charged residues are involved in virus assembly by mediating interaction between
      the membrane (M) protein carboxy tail and nucleocapsids. To determine the
      importance of these negatively charged residues, a series of alanine and other
      charged-residue substitutions were introduced in place of those in the N gene
      within a mouse hepatitis coronavirus A59 infectious clone. Aspartic acid residues
      440 and 441 were identified as functionally important. Viruses could not be
      isolated when both residues were replaced by positively charged amino acids. When
      either amino acid was replaced by a positively charged residue or both were
      changed to alanine, viruses were recovered that contained second-site changes
      within N, but not in the M or envelope protein. The compensatory role of the new
      changes was confirmed by the construction of new viruses. A few viruses were
      recovered that retained the D441-to-arginine change and no compensatory changes.
      These viruses exhibited a small-plaque phenotype and produced significantly less
      virus. Overall, results from our analysis of a large panel of plaque-purified
      recovered viruses indicate that the negatively charged residues at positions 440
      and 441 are key residues that appear to be involved in virus assembly.

PMID- 16611894
TI  - Characterization of transcription factor binding to human papillomavirus type 16
      DNA during cellular differentiation.
AB  - Human papillomaviruses (HPVs) require terminal differentiation of the host cell
      to produce infectious virions. The process of viral maturation involves a variety
      of changes in the expression/activity of host proteins that lead to high-level
      replication of the viral genome and expression of the late viral genes. Although
      the late promoter regions of HPV type 16 (HPV-16) are still not fully
      characterized, differentiation-dependent regulation of viral genes is thought to
      involve changes in the binding of host cell transcription factors to the viral
      promoter and regulatory regions. Currently, very little is known about specific
      cellular transcription factors involved in this process. We used the Panomics
      TransSignal protein/DNA array to identify changes in the levels of cellular
      transcription factors during methylcellulose-induced differentiation of W12
      (20863) cells containing HPV-16. We then identified the differentially expressed
      transcription factors that specifically bind to HPV-16 DNA, including the known
      promoter and regulatory regions. We have validated the results obtained from the
      Panomics array by Western blot analysis. Furthermore, by chromatin
      immunoprecipitation assays, we have shown that many of the transcription factors
      identified in the above screen bind to the HPV-16 promoter/regulatory sequences
      in vivo and that the level of this binding is increased during differentiation.
      This approach identified approximately 30 transcription factors that specifically
      bind to HPV-16 sequences and may be involved in regulating HPV-16 transcription
      during differentiation. Although some of these transcription factors have
      previously been suggested to be involved in HPV-16 transcription, a number of
      them represent novel viral DNA-host protein interactions.

PMID- 16611895
TI  - Cellular topoisomerase I modulates origin binding by bovine papillomavirus type 1
      E1.
AB  - In addition to viral proteins E1 and E2, bovine papillomavirus type 1 (BPV1)
      depends heavily on host replication machinery for genome duplication. It was
      previously shown that E1 binds to and recruits cellular replication proteins to
      the BPV1 origin of replication, including DNA polymerase alpha-primase,
      replication protein A (RPA), and more recently, human topoisomerase I (Topo I).
      Here, we show that Topo I specifically stimulates the origin binding of E1
      severalfold but has no effect on nonorigin DNA binding. This is highly specific,
      as binding to nonorigin DNA is not stimulated, and other cellular proteins that
      bind E1, such as RPA and polymerase alpha-primase, show no such effect. The
      stimulation of E1's origin binding by Topo I is not synergistic with the
      stimulation by E2. Although the enhanced origin binding of E1 by Topo I requires
      ATP and Mg2+ for optimal efficiency, ATP hydrolysis is not required. Using an
      enzyme-linked immunosorbent assay, we showed that the interaction between E1 and
      Topo I is decreased in the presence of DNA. Our results suggest that Topo I
      participates in the initiation of papillomavirus DNA replication by enhancing E1
      binding to the BPV1 origin.

PMID- 16611896
TI  - Hepatitis C virus core protein inhibits tumor necrosis factor alpha-mediated
      apoptosis by a protective effect involving cellular FLICE inhibitory protein.
AB  - We have previously shown that hepatitis C virus (HCV) core protein modulates
      multiple cellular processes, including those that inhibit tumor necrosis factor
      alpha (TNF-alpha)-mediated apoptosis. In this study, we have investigated the
      signaling mechanism for inhibition of TNF-alpha-mediated apoptosis in human
      hepatoma (HepG2) cells expressing core protein alone or in context with other HCV
      proteins. Activation of caspase-3 and the cleavage of DNA repair enzyme poly(ADP
      ribose) polymerase were inhibited upon TNF-alpha exposure in HCV core protein
      expressing HepG2 cells. In vivo protein-protein interaction studies displayed an
      association between TNF receptor 1 (TNFR1) and TNFR1-associated death domain
      protein (TRADD), suggesting that the core protein does not perturb this
      interaction. A coimmunoprecipitation assay also suggested that HCV core protein
      does not interfere with the TRADD-Fas-associated death domain protein (FADD)
      procaspase-8 interaction. Further studies indicated that HCV core protein
      expression inhibits caspase-8 activation by sustaining the expression of cellular
      FLICE (FADD-like interleukin-1beta-converting enzyme)-like inhibitory protein (c
      FLIP). Similar observations were also noted upon expression of core protein in
      context to other HCV proteins expressed from HCV full-length plasmid DNA or a
      replicon. A decrease in endogenous c-FLIP by specific small interfering RNA
      induced TNF-alpha-mediated apoptotic cell death and caspase-8 activation. Taken
      together, our results suggested that the TNF-alpha-induced apoptotic pathway is
      inhibited by a sustained c-FLIP expression associated with the expression of HCV
      core protein, which may play a role in HCV-mediated pathogenesis.

PMID- 16611897
TI  - Base pairing between the 5' half of epsilon and a cis-acting sequence, phi, makes
      a contribution to the synthesis of minus-strand DNA for human hepatitis B virus.
AB  - Synthesis of minus-strand DNA of human hepatitis B virus (HBV) can be divided
      into three phases: initiation of DNA synthesis, the template switch, and
      elongation of minus-strand DNA. Although much is known about minus-strand DNA
      synthesis, the mechanism(s) by which this occurs has not been completely
      elucidated. Through a deletion analysis, we have identified a cis-acting element
      involved in minus-strand DNA synthesis that lies within a 27-nucleotide region
      between DR2 and the 3' copy of DR1. A subset of this region (termed Phi) has been
      hypothesized to base pair with the 5' half of epsilon (H. Tang and A. McLachlan,
      Virology, 303:199-210, 2002). To test the proposed model, we used a genetic
      approach in which multiple sets of variants that disrupted and then restored
      putative base pairing between the 5' half of epsilon and phi were analyzed.
      Primer extension analysis, using two primers simultaneously, was performed to
      measure encapsidated pregenomic RNA (pgRNA) and minus-strand DNA synthesized in
      cell culture. The efficiency of minus-strand DNA synthesis was defined as the
      amount of minus-strand DNA synthesized per encapsidation event. Our results
      indicate that base pairing between phi and the 5' half of epsilon contributes to
      efficient minus-strand DNA synthesis. Additional results are consistent with the
      idea that the primary sequence of phi and/or epsilon also contributes to
      function. How base pairing between phi and epsilon contributes to minus-strand
      DNA synthesis is not known, but a simple speculation is that phi base pairs with
      the 5' half of epsilon to juxtapose the donor and acceptor sites to facilitate
      the first-strand template switch.

PMID- 16611898
TI  - Subunit stoichiometry of human immunodeficiency virus type 1 envelope
      glycoprotein trimers during virus entry into host cells.
AB  - The envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1)
      function as a homotrimer of gp120/gp41 heterodimers to support virus entry.
      During the process of virus entry, an individual HIV-1 envelope glycoprotein
      trimer binds the cellular receptors CD4 and CCR5/CXCR4 and mediates the fusion of
      the viral and the target cellular membranes. By studying the function of
      heterotrimers between wild-type and nonfunctional mutant envelope glycoproteins,
      we found that two wild-type subunits within an envelope glycoprotein trimer are
      required to support virus entry. Complementation between HIV-1 envelope
      glycoprotein mutants defective in different functions to allow virus entry was
      not evident. These results assist our understanding of the mechanisms whereby the
      HIV-1 envelope glycoproteins mediate virus entry and membrane fusion and guide
      attempts to inhibit these processes.

PMID- 16611899
TI  - The Us9 gene of bovine herpesvirus 1 (BHV-1) effectively complements a Us9-null
      strain of BHV-5 for anterograde transport, neurovirulence, and neuroinvasiveness
      in a rabbit model.
AB  - The alphaherpesvirus envelope protein Us9 is a type II viral membrane protein
      that is required for anterograde spread of bovine herpesvirus 5 (BHV-5) infection
      from the olfactory receptor neurons to the brain. In a rabbit seizure model, Us9
      deleted BHV-5 failed to invade the central nervous system (CNS) following
      intranasal infection. However, when injected directly into the olfactory bulb,
      retrograde-spread infection from the olfactory bulb (OB) to the piriform cortex
      and other areas connected to the OB was not affected. In contrast to BHV-5, wild
      type BHV-1 failed to invade the CNS following intranasal infection. In this
      study, we show that mature BHV-1 Us9 is a 30- to 32-kDa protein, whereas mature
      BHV-5 Us9 is an 18- to 20-kDa protein. In vitro, BHV-1 Us9 is expressed at 3 h
      postinfection (hpi), whereas BHV-5 Us9 is expressed at 6 hpi. Despite these
      differences, BHV-1 Us9 not only complemented for BHV-5 Us9 and rescued the
      anterograde-spread defect of the BHV-5 Us9-deleted virus but conferred increased
      neurovirulence and neuroinvasiveness in our rabbit seizure model. Rabbits
      infected with BHV-5 expressing BHV-1 Us9 showed severe neurological signs at 5
      days postinfection, which was 1 to 2 days earlier than BHV-5 wild-type or Us9
      reverted BHV-5 virus. The data underscore the importance of both Us9 genes for
      virion anterograde transport and neuroinvasiveness. However, Us9 is not the
      determinant of the differential neuropathogenesis of BHV-1 and BHV-5.

PMID- 16611900
TI  - Activation of focal adhesion kinase by hepatitis B virus HBx protein: multiple
      functions in viral replication.
AB  - The hepatitis B virus (HBV) X protein (HBx) is a multifunctional regulator of
      cellular signal transduction and transcription pathways and has a critical role
      in HBV replication. Much of the cytoplasmic signal transduction activity
      associated with HBx expression and its stimulation of viral replication is
      attributable to HBx-induced activation of calcium signaling pathways involving
      Pyk2 and Src tyrosine kinases. To further characterize upstream signal
      transduction pathways that are required for HBx activity, including activation of
      Src and mitogen-activated protein kinase (MAPK) cascades, we determined whether
      focal adhesion kinase (FAK), a known regulator of Src family kinases and the
      other member of the Pyk2/FAK kinase family, is activated by HBx. We report that
      HBx activates FAK and that FAK activation is important for multiple HBx
      functions. Dominant inhibiting forms of FAK blocked HBx activation of Src kinases
      and downstream signal transduction, HBx stimulation of NF-kappaB and AP-1
      dependent transcription, and HBV DNA replication. We also demonstrate that HBx
      induced activation of FAK is dependent on cellular calcium signaling, which is
      modulated by HBx. Moreover, prolonged expression of HBx increases both FAK
      activity and its level of expression. FAK activation may play a role in cellular
      transformation and cancer progression. HBx stimulation of FAK activity and
      abundance may also be relevant as a potential cofactor in HBV-associated
      hepatocellular carcinoma.

PMID- 16611901
TI  - Expression profiles of endogenous retroviruses in Old World monkeys.
AB  - Human endogenous retroviruses (HERVs) are a major component of the human genome
      and an active part of the transcriptome. Some HERVs play vital biological roles,
      while others potentially contribute to diseases. Many HERVs are relatively new in
      the primate genome, having entered or expanded after the lineages leading to the
      platyrrhines (New World monkeys) and catarrhines (Old World monkeys and apes)
      separated. Most HERVs are active in at least some tissues, though tissue
      specificity is common for most elements. We analyzed multiple tissues from
      several Old World monkeys using retroviral pol-based DNA microarrays and
      quantitative PCR methods to determine their ERV expression profiles. The results
      demonstrate that while many ERVs are active in nonhuman primates, overall the
      tissue expression specificity is unique to each species. Most striking is that
      while the majority of HERVs analyzed in this study are expressed in human brain,
      almost none are expressed in Old World monkey brains or are only weakly
      expressed.

PMID- 16611902
TI  - Negative regulation of the alpha interferon-induced antiviral response by the
      Ras/Raf/MEK pathway.
AB  - Interferon (IFN) is one of the molecules released by virus-infected cells,
      resulting in the establishment of an antiviral state within infected and
      neighboring cells. IFN-induced antiviral response may be subject to modulation by
      the cellular signaling environment of host cells which impact the effectiveness
      of viral replication. Here, we show that cells with an activated Ras/Raf/MEK
      signaling cascade allow propagation of viruses in the presence of IFN. Ras
      transformed (RasV12) and vector control NIH 3T3 cells were infected with
      vesicular stomatitis virus (VSV) or an IFN-sensitive vaccinia virus (delE3L) in
      the presence of alpha interferon. While IFN protected vector control cells from
      infection by both viruses, RasV12 cells were susceptible to viral infection
      regardless of the presence of IFN. IFN sensitivity was restored in RasV12 cells
      upon RNA interference (RNAi) knockdown of Ras. We further investigated which
      elements downstream of Ras are responsible for counteracting IFN-induced
      antiviral responses. A Ras effector domain mutant that can only stimulate the Raf
      kinase family of effectors was able to suppress the IFN response and allow VSV
      replication. IFN-induced antiviral mechanisms were also restored in RasV12 cells
      by treatment with a MEK inhibitor (U0126 or PD98059). Moreover, by using RNAi to
      MEK1 and MEK2, we determined that MEK2, rather than MEK1, is responsible for
      suppression of the IFN response. In conclusion, our results suggest that
      activation of the Ras/Raf/MEK pathway downregulates IFN-induced antiviral
      response.

PMID- 16611903
TI  - Different modes of human papillomavirus DNA replication during maintenance.
AB  - Human papillomavirus (HPV) begins its life cycle by infecting the basal cells of
      the epithelium. Within these proliferating cells, the viral genomes are
      replicated, maintained, and passed on to the daughter cells. Using HPV episome
      containing cell lines that were derived from naturally infected cervical tissues,
      we investigated the mode by which the viral DNAs replicate in these cells. We
      observed that, whereas HPV16 DNA replicated in an ordered once-per-S-phase manner
      in W12 cells, HPV31 DNA replicated via a random-choice mechanism in CIN612 cells.
      However, when HPV16 and HPV31 DNAs were separately introduced into an alternate
      keratinocyte cell line NIKS, they both replicated randomly. This indicates that
      HPV DNA is inherently capable of replicating by either random-choice or once-per
      S-phase mechanisms and that the mode of HPV DNA replication is dependent on the
      cells that harbor the viral episome. High expression of the viral replication
      protein E1 in W12 cells converted HPV16 DNA replication to random-choice
      replication and, as such, it appears that the mode of HPV DNA replication in
      proliferating cells is dependent on the presence or the increased level of this
      protein in the host cell. The implications of these observations on maintenance,
      latency, and persistence are discussed.

PMID- 16611904
TI  - In vitro microbicidal activity of the nonnucleoside reverse transcriptase
      inhibitor (NNRTI) UC781 against NNRTI-resistant human immunodeficiency virus type
      1.
AB  - The nonnucleoside reverse transcriptase inhibitor (NNRTI) UC781 is under
      development as a microbicide to prevent sexual transmission of the human
      immunodeficiency virus type 1 (HIV-1). However, NNRTI-resistant HIV-1 is
      increasingly prevalent in the infected population, and one of the concerns for
      NNRTI-based microbicides is that they will be ineffective against drug-resistant
      virus and may in fact selectively transmit NNRTI-resistant virus. We evaluated
      the microbicidal activity of UC781 against UC781-resistant (UCR), efavirenz
      resistant (EFVR), and nevirapine-resistant (NVPR) strains in a variety of
      microbicide-relevant tests, including inactivation of cell-free virus, inhibition
      of cell-to-cell HIV-1 transmission, and the ability of UC781 pretreatment to
      protect cells from subsequent infection in the absence of exogenous drug. UC781
      was 10- to 100-fold less effective against NNRTI-resistant HIV-1 compared to wild
      type (wt) virus in each of these tests, with UC781 microbicidal activity against
      the various virus strains being wt > or = NVPR > UCR > or = EFVR. Breakthrough
      experiments using UC781-pretreated cells and mixtures of wt and NNRTI-resistant
      HIV-1 showed that UC781-pretreatment selected for NNRTI-resistant HIV-1. However,
      the efficacy of UC781 was dose dependent, and 25 microM UC781 provided
      essentially equivalent microbicidal activity against NNRTI-resistant and wt
      virus. The amount of UC781 in topical microbicide formulations under current
      development is approximately 100-fold greater than this concentration, so
      transmission of NNRTI-resistant virus may not be an issue at these microbicide
      formulation levels of UC781. Nonetheless, the reduced microbicidal activity of
      UC781 against NNRTI-resistant HIV-1 suggests that additional antiviral agents
      should be included in NNRTI-based microbicide formulations.

PMID- 16611905
TI  - Recombinant vesicular stomatitis virus vectors expressing herpes simplex virus
      type 2 gD elicit robust CD4+ Th1 immune responses and are protective in mouse and
      guinea pig models of vaginal challenge.
AB  - Recombinant vesicular stomatitis virus (rVSV) vectors offer an attractive
      approach for the induction of robust cellular and humoral immune responses
      directed against human pathogen target antigens. We evaluated rVSV vectors
      expressing full-length glycoprotein D (gD) from herpes simplex virus type 2 (HSV
      2) in mice and guinea pigs for immunogenicity and protective efficacy against
      genital challenge with wild-type HSV-2. Robust Th1-polarized anti-gD immune
      responses were demonstrated in the murine model as measured by induction of gD
      specific cytotoxic T lymphocytes and increased gamma interferon expression. The
      isotype makeup of the serum anti-gD immunoglobulin G (IgG) response was
      consistent with the presence of a Th1-CD4+ anti-gD response, characterized by a
      high IgG2a/IgG1 IgG subclass ratio. Functional anti-HSV-2 neutralizing serum
      antibody responses were readily demonstrated in both guinea pigs and mice that
      had been immunized with rVSV-gD vaccines. Furthermore, guinea pigs and mice were
      prophylactically protected from genital challenge with high doses of wild-type
      HSV-2. In addition, guinea pigs were highly protected against the establishment
      of latent infection as evidenced by low or absent HSV-2 genome copies in dorsal
      root ganglia after virus challenge. In summary, rVSV-gD vectors were successfully
      used to elicit potent anti-gD Th1-like cellular and humoral immune responses that
      were protective against HSV-2 disease in guinea pigs and mice.

PMID- 16611906
TI  - Mutations in the endodomain of Sindbis virus glycoprotein E2 define sequences
      critical for virus assembly.
AB  - Envelopment of Sindbis virus at the plasma membrane is a multistep process in
      which an initial step is the association of the E2 protein via a cytoplasmic
      endodomain with the preassembled nucleocapsid. Sindbis virus is vectored in
      nature by blood-sucking insects and grows efficiently in a number of avian and
      mammalian vertebrate hosts. The assembly of Sindbis virus, therefore, must occur
      in two very different host cell environments. Mammalian cells contain cholesterol
      which insect membranes lack. This difference in membrane composition may be
      critical in determining what requirements are placed on the E2 tail for virus
      assembly. To examine the interaction between the E2 tail and the nucleocapsid in
      Sindbis virus, we have produced substitutions and deletions in a region of the E2
      tail (E2 amino acids 408 to 415) that is initially integrated into the
      endoplasmic reticulum. This sequence was identified as being critical for
      nucleocapsid binding in an in vitro peptide protection assay. The effects of
      these mutations on virus assembly and function were determined in both vertebrate
      and invertebrate cells. Amino acid substitutions (at positions E2: 408, 410, 411,
      and 413) reduced infectious virus production in a position-dependent fashion but
      were not efficient in disrupting assembly in mammalian cells. Deletions in the E2
      endodomain (delta406-407, delta409-411, and delta414-417) resulted in the failure
      to assemble virions in mammalian cells. Electron microscopy of BHK cells
      transfected with these mutants revealed assembly of nucleocapsids that failed to
      attach to membranes. However, introduction of these deletion mutants into insect
      cells resulted in the assembly of virus-like particles but no assayable
      infectivity. These data help define protein interactions critical for virus
      assembly and suggest a fundamental difference between Sindbis virus assembly in
      mammalian and insect cells.

PMID- 16611907
TI  - Importance of the N-distal AP-2 binding element in Nef for simian
      immunodeficiency virus replication and pathogenicity in rhesus macaques.
AB  - Point mutations in SIVmac239 Nef disrupting CD4 downmodulation and enhancement of
      virion infectivity attenuate viral replication in acutely infected rhesus
      macaques, but changes selected later in infection fully restore Nef function (A.
      J. Iafrate et al., J. Virol. 74:9836-9844, 2000). To further evaluate the
      relevance of these Nef functions for viral persistence and disease progression,
      we analyzed an SIVmac239 Nef mutant containing a deletion of amino acids Q64 to
      N67 (delta64-67Nef). This mutation inactivates the N-distal AP-2 clathrin adaptor
      binding element and disrupts the abilities of Nef to downregulate CD4, CD28 and
      CXCR4 and to stimulate viral replication in vitro. However, it does not impair
      the downmodulation of CD3 and class I major histocompatibility complex (MHC-I) or
      MHC-II and the upregulation of the MHC-II-associated invariant chain, and it has
      only a moderate effect on the enhancement of virion infectivity. Replication of
      the delta64-67Nef variant in acutely infected macaques was intermediate between
      grossly nef-deleted and wild-type SIVmac239. Subsequently, three of six macaques
      developed moderate to high viral loads and developed disease, whereas the
      remaining animals efficiently controlled SIV replication and showed a more
      attenuated clinical course of infection. Sequence analysis revealed that the
      deletion in nef was not repaired in any of these animals. However, some changes
      that slightly enhanced the ability of Nef to downmodulate CD4 and moderately
      increased Nef-mediated enhancement of viral replication and infectivity in vitro
      were observed in macaques developing high viral loads. Our results imply that
      both the Nef functions that were disrupted by the delta64-67 mutation and the
      activities that remained intact contribute to viral pathogenicity.

PMID- 16611908
TI  - Junctional adhesion molecule 1 is a functional receptor for feline calicivirus.
AB  - The life cycle of calicivirus is not fully understood because most of the viruses
      cannot be propagated in tissue culture cells. We studied the mechanism of
      calicivirus entry into cells using feline calicivirus (FCV), a cultivable
      calicivirus. From the cDNA library of Crandell-Rees feline kidney (CRFK) cells,
      feline junctional adhesion molecule 1 (JAM-1), an immunoglobulin-like protein
      present in tight junctions, was identified as a cellular-binding molecule of the
      FCV F4 strain, a prototype strain in Japan. Feline JAM-1 expression in
      nonpermissive hamster lung cells led to binding and infection by F4 and all other
      strains tested. An anti-feline JAM-1 antibody reduced the binding of FCV to
      permissive CRFK cells and strongly suppressed the cytopathic effect (CPE) and FCV
      progeny production in infected cells. Some strains of FCV, such as F4 and F25,
      have the ability to replicate in Vero cells. We found that regardless of
      replication ability, FCV bound to Vero and 293T cells via simian and human JAM-1,
      respectively. In Vero cells, an anti-human JAM-1 antibody inhibited binding, CPE,
      and progeny production by F4 and F25. In addition, feline JAM-1 expression
      permitted FCV infection in 293T cells. Taken together, our results demonstrate
      that feline JAM-1 is a functional receptor for FCV, simian JAM-1 also functions
      as a receptor for some strains of FCV, and the interaction between FCV and JAM-1
      molecules may be a determinant of viral tropism. This is the first report
      concerning a functional receptor for the viruses in the family Caliciviridae.

PMID- 16611909
TI  - DNA binding activity of the herpes simplex virus type 1 origin binding protein,
      UL9, can be modulated by sequences in the N terminus: correlation between
      transdominance and DNA binding.
AB  - UL9, the origin binding protein of herpes simplex virus type 1, is a member of
      the SF2 family of helicases. Cotransfection of cells with infectious viral DNA
      and plasmids expressing either full-length UL9 or the C-terminal DNA binding
      domain alone results in the drastic inhibition of plaque formation which can be
      partially relieved by an insertion mutant lacking DNA binding activity. In this
      work, C-terminally truncated mutants which terminate at or near residue 359 were
      shown to potentiate plaque formation, while other C-terminal truncations were
      inhibitory. Thus, residues in the N-terminal region appear to regulate the
      inhibitory properties of UL9. To identify which residues were involved in this
      regulation, a series of N-terminally truncated mutants were constructed which
      contain the DNA binding domain and various N-terminal extensions. Mutants whose N
      terminus is either at residue 494 or 535 were able to bind the origin efficiently
      and were inhibitory to plaque formation, whereas constructs whose N terminus is
      at residue 304 or 394 were defective in origin binding activity and were able to
      relieve inhibition. Since UL9 is required for viral infection at early but not
      late times and is inhibitory to infection when overexpressed, we propose that the
      DNA binding activities of UL9 are regulated during infection. For infection to
      proceed, UL9 may need to switch from a DNA binding to a non-DNA binding mode, and
      we suggest that sequences residing in the N terminus play a role in this switch.

PMID- 16611910
TI  - Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs
      and displays potent antiviral activity against select virus infections in vivo.
AB  - Type III interferons (IFNs) (interleukin-28/29 or lambda interferon [IFN-lambda])
      are cytokines with IFN-like activities. Here we show that several classes of
      viruses induce expression of IFN-lambda1 and -lambda2/3 in similar patterns. The
      IFN-lambdas were-unlike alpha/beta interferon (IFN-alpha/beta)-induced directly
      by stimulation with IFN-alpha or -lambda, thus identifying type III IFNs as IFN
      stimulated genes. In vitro assays revealed that IFN-lambdas have appreciable
      antiviral activity against encephalomyocarditis virus (EMCV) but limited activity
      against herpes simplex virus type 2 (HSV-2), whereas IFN-alpha potently
      restricted both viruses. Using three murine models for generalized virus
      infections, we found that while recombinant IFN-alpha reduced the viral load
      after infection with EMCV, lymphocytic choriomeningitis virus (LCMV), and HSV-2,
      treatment with recombinant IFN-lambda in vivo did not affect viral load after
      infection with EMCV or LCMV but did reduce the hepatic viral titer of HSV-2. In a
      model for a localized HSV-2 infection, we further found that IFN-lambda
      completely blocked virus replication in the vaginal mucosa and totally prevented
      development of disease, in contrast to IFN-alpha, which had a more modest
      antiviral activity. Finally, pretreatment with IFN-lambda enhanced the levels of
      IFN-gamma in serum after HSV-2 infection. Thus, type III IFNs are expressed in
      response to most viruses and display potent antiviral activity in vivo against
      select viruses. The discrepancy between the observed antiviral activity in vitro
      and in vivo may suggest that IFN-lambda exerts a significant portion of its
      antiviral activity in vivo via stimulation of the immune system rather than
      through induction of the antiviral state.

PMID- 16611911
TI  - Diverse effects of cyclosporine on hepatitis C virus strain replication.
AB  - Recently, a production system for infectious particles of hepatitis C virus (HCV)
      utilizing the genotype 2a JFH1 strain has been developed. This strain has a high
      capacity for replication in the cells. Cyclosporine (CsA) has a suppressive
      effect on HCV replication. In this report, we characterize the anti-HCV effect of
      CsA. We observe that the presence of viral structural proteins does not influence
      the anti-HCV activity of CsA. Among HCV strains, the replication of genotype 1b
      replicons was strongly suppressed by treatment with CsA. In contrast, JFH1
      replication was less sensitive to CsA and its analog, NIM811. Replication of JFH1
      did not require the cellular replication cofactor, cyclophilin B (CyPB). CyPB
      stimulated the RNA binding activity of NS5B in the genotype 1b replicon but not
      the genotype 2a JFH1 strain. These findings provide an insight into the
      mechanisms of diversity governing virus-cell interactions and in the sensitivity
      of these strains to antiviral agents.

PMID- 16611912
TI  - Differential chemokine expression following respiratory virus infection reflects
      Th1- or Th2-biased immunopathology.
AB  - Respiratory syncytial virus (RSV) is a major viral pathogen of infants that also
      reinfects adults. During RSV infection, inflammatory host cell recruitment to the
      lung plays a central role in determining disease outcome. Chemokines mediate cell
      recruitment to sites of inflammation and are influenced by, and influence, the
      production of cytokines. We therefore compared chemokine production in a mouse
      model of immunopathogenic RSV infection in which either Th1 or Th2
      immunopathology is induced by prior sensitization to individual RSV proteins.
      Chemokine expression profiles were profoundly affected by the nature of the
      pulmonary immunopathology: "Th2" immunopathology in BALB/c mice was associated
      with increased and prolonged expression of CCL2 (MCP-1), CXCL10 (IP-10), and
      CCL11 (eotaxin) starting within 24 h of challenge. C57BL/6 mice with "Th2"
      pathology (enabled by a deficiency of CD8+ cells) also showed increased CCL2
      production. No differences in chemokine receptor expression were detected.
      Chemokine blockers may therefore be of use for children with bronchiolitis.

PMID- 16611913
TI  - Cellular stress rather than stage of the cell cycle enhances the replication and
      plating efficiencies of herpes simplex virus type 1 ICP0- viruses.
AB  - This lab reported previously that the plating efficiency of a herpes simplex
      virus type 1 ICP0-null mutant was enhanced upon release from an isoleucine block
      which synchronizes cells to G1 phase (W. Cai and P. A. Schaffer, J. Virol.
      65:4078-4090, 1991). Peak plating efficiency occurred as cells cycled out of G1
      and into S phase, suggesting that the enhanced plating efficiency was due to
      cellular activities present in late G1/early S phase. We have found, however,
      that the enhanced plating efficiency did not occur when cells were synchronized
      by alternative methods. We now report that the plating efficiency of ICP0-
      viruses is not enhanced at a particular stage of the cell cycle but rather is
      enhanced by specific cellular stresses. Both the plating and replication
      efficiencies of ICP0- viruses were enhanced as much as 25-fold to levels similar
      to that of wild-type virus when monolayers were heat shocked prior to infection.
      In addition to heat shock, UV-C irradiation but not cold shock of monolayers
      prior to infection resulted in enhanced plating efficiency. We further report
      that the effect of cellular stress is transient and that cell density rather than
      age of the monolayers is the primary determinant of ICP0- virus plating
      efficiency. As both cell stress and ICP0 are required for efficient reactivation
      from latency, the identification of cellular activities that complement ICP0-
      viruses may lead to the identification of cellular activities that are important
      for reactivation from neuronal latency.

PMID- 16611914
TI  - Sendai virus infection induces efficient adaptive immunity independently of type
      I interferons.
AB  - Adaptive immunity in response to virus infection involves the generation of Th1
      cells, cytotoxic T cells, and antibodies. This type of immune response is crucial
      for the clearance of virus infection and for long-term protection against
      reinfection. Type I interferons (IFNs), the primary innate cytokines that control
      virus growth and spreading, can influence various aspects of adaptive immunity.
      The development of antiviral immunity depends on many viral and cellular factors,
      and the extent to which type I IFNs contribute to the generation of adaptive
      immunity in response to a viral infection is controversial. Using two strains
      (Cantell and 52) of the murine respiratory Sendai virus (SeV) with differential
      abilities to induce type I IFN production from infected cells, together with type
      I IFN receptor-deficient mice, we examined the role of type I IFNs in the
      generation of adaptive immunity. Our results show that type I IFNs facilitate
      virus clearance and enhance the migration and maturation of dendritic cells after
      SeV infection in vivo; however, soon after infection, mice clear the virus from
      their lungs and efficiently generate cytotoxic T cells independently of type I
      IFN signaling. Furthermore, animals that are unresponsive to type I IFN develop
      long-term anti-SeV immunity, including CD8+ T cells and antibodies.
      Significantly, this memory response is able to protect mice against challenge
      with a lethal dose of virus. In conclusion, our results show that primary and
      secondary anti-SeV adaptive immunities are developed normally in the absence of
      type I IFN responsiveness.

PMID- 16611915
TI  - Prion infection of oral and nasal mucosa.
AB  - Centrifugal spread of the prion agent to peripheral tissues is postulated to
      occur by axonal transport along nerve fibers. This study investigated the
      distribution of the pathological isoform of the protein (PrP(Sc)) in the tongues
      and nasal cavities of hamsters following intracerebral inoculation of the HY
      strain of the transmissible mink encephalopathy (TME) agent. We report that
      PrP(Sc) deposition was found in the lamina propria, taste buds, and stratified
      squamous epithelium of fungiform papillae in the tongue, as well as in skeletal
      muscle cells. Using laser scanning confocal microscopy, PrP(Sc) was localized to
      nerve fibers in each of these structures in the tongue, neuroepithelial taste
      cells of the taste bud, and, possibly, epithelial cells. This PrP(Sc)
      distribution was consistent with a spread of HY TME agent along both
      somatosensory and gustatory cranial nerves to the tongue and suggests subsequent
      synaptic spread to taste cells and epithelial cells via peripheral synapses. In
      the nasal cavity, PrP(Sc) accumulation was found in the olfactory and vomeronasal
      epithelium, where its location was consistent with a distribution in cell bodies
      and apical dendrites of the sensory neurons. Prion spread to these sites is
      consistent with transport via the olfactory nerve fibers that descend from the
      olfactory bulb. Our data suggest that epithelial cells, neuroepithelial taste
      cells, or olfactory sensory neurons at chemosensory mucosal surfaces, which
      undergo normal turnover, infected with the prion agent could be shed and play a
      role in the horizontal transmission of animal prion diseases.

PMID- 16611916
TI  - Retrovirus-induced oxidative stress with neuroimmunodegeneration is suppressed by
      antioxidant treatment with a refined monosodium alpha-luminol (Galavit).
AB  - Oxidative stress is involved in many human neuroimmunodegenerative diseases,
      including human immunodeficiency virus disease/AIDS. The retrovirus ts1, a mutant
      of Moloney murine leukemia virus, causes oxidative stress and progressive neuro-
      and immunopathology in mice infected soon after birth. These pathological changes
      include spongiform neurodegeneration, astrogliosis, thymic atrophy, and T-cell
      depletion. Astrocytes and thymocytes are directly infected and killed by ts1.
      Neurons are not infected, but they also die, most likely as an indirect result of
      local glial infection. Cytopathic effects of ts1 infection in cultured astrocytes
      are associated with accumulation of the viral envelope precursor protein gPr80env
      in the endoplasmic reticulum (ER), which triggers ER stress and oxidative stress.
      We have reported (i) that activation of the Nrf2 transcription factor and
      upregulation of antioxidative defenses occurs in astrocytes infected with ts1 in
      vitro and (ii) that some ts1-infected astrocytes survive infection by
      mobilization of these pathways. Here, we show that treatment with a refined
      monosodium alpha-luminol (Galavit; GVT) suppresses oxidative stress and Nrf2
      activation in cultured ts1-infected astrocytes. GVT treatment also inhibits the
      development of spongiform encephalopathy and gliosis in the central nervous
      system (CNS) in ts1-infected mice, preserves normal cytoarchitecture in the
      thymus, and delays paralysis, thymic atrophy, wasting, and death. GVT treatment
      of infected mice reduces ts1-induced oxidative stress, cell death, and
      pathogenesis in both the CNS and thymus of treated animals. These studies suggest
      that oxidative stress mediates ts1-induced neurodegeneration and T-cell loss.

PMID- 16611918
TI  - E2 proteins from high- and low-risk human papillomavirus types differ in their
      ability to bind p53 and induce apoptotic cell death.
AB  - The E2 proteins from oncogenic (high-risk) human papillomaviruses (HPVs) can
      induce apoptotic cell death in both HPV-transformed and non-HPV-transformed
      cells. Here we show that the E2 proteins from HPV type 6 (HPV6) and HPV11, two
      nononcogenic (low-risk) HPV types, fail to induce apoptosis. Unlike the high-risk
      HPV16 E2 protein, these low-risk E2 proteins fail to bind p53 and fail to induce
      p53-dependent transcription activation. Interestingly, neither the ability of p53
      to activate transcription nor the ability of p53 to bind DNA, are required for
      HPV16 E2-induced apoptosis in non-HPV-transformed cells. However, mutations that
      reduce the binding of the HPV16 E2 protein to p53 inhibit E2-induced apoptosis in
      non-HPV-transformed cells. In contrast, the interaction between HPV16 E2 and p53
      is not required for this E2 protein to induce apoptosis in HPV-transformed cells.
      Thus, our data suggest that this high-risk HPV E2 protein induces apoptosis via
      two pathways. One pathway involves the binding of E2 to p53 and can operate in
      both HPV-transformed and non-HPV-transformed cells. The second pathway requires
      the binding of E2 to the viral genome and can only operate in HPV-transformed
      cells.

PMID- 16611917
TI  - Hexamethylbisacetamide remodels the human immunodeficiency virus type 1 (HIV-1)
      promoter and induces Tat-independent HIV-1 expression but blunts cell activation.
AB  - Hexamethylbisacetamide (HMBA) induces human immunodeficiency virus type 1 (HIV-1)
      gene expression in latently infected T-cell and monocytoid cell lines. We find
      that HMBA activation of viral expression is Tat independent but, like Tat,
      increases the efficiency of elongation of the HIV-1 promoter (long terminal
      repeat [LTR]) transcripts. Further, exposure to HMBA induces chromatin remodeling
      at nucleosome 1 (Nuc-1) near the start site of LTR transcription but does so
      without increasing histone acetylation or altering histone methylation near Nuc
      1. Of note, despite enhanced proviral expression, HMBA suppressed HIV infection
      ex vivo in primary blood mononuclear cell (PBMC) cultures. Treatment with HMBA
      did not alter expression of the HIV coreceptors, CCR5 and CXCR4, in PBMCs but
      down-regulated CD4. Finally, HMBA interferes with cell proliferation and
      activation; it suppressed expression of Ki67 and CD25 and in PBMCs exposed to
      mitogen. As HMBA has been tested in oncology trials, its unusual properties make
      it a useful reagent for future studies of HIV promoter regulation and a novel
      prototype molecule for therapeutics that abort the latent proviral state of
      chronic HIV infection.

PMID- 16611919
TI  - Human cytomegalovirus infection elicits a glycoprotein M (gM)/gN-specific virus
      neutralizing antibody response.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous human pathogen that infects 40 to
      90% of adult human populations. HCMV infections are often asymptomatic in healthy
      individuals but can cause severe organ and life-threatening disease in
      immunocompromised patients. The antiviral antibody response to HCMV infection is
      complex and is known to include virus-neutralizing antibody production against
      surface glycoproteins encoded by HCMV. We have investigated the human antibody
      response to a complex of HCMV surface glycoproteins composed of glycoprotein M
      (gM)/gN, the gene products of the UL100 and UL73 open reading frames. Mouse
      monoclonal antibodies generated against gM/gN have previously been shown to
      neutralize HCMV infection of human fibroblasts in vitro. To determine whether
      human antibodies reactive with the gM/gN complex possess virus-neutralizing
      properties, we isolated human antibodies reactive with gM/gN from pooled human
      HCMV hyperimmune globulin by affinity purification using recombinant gM/gN. The
      affinity-purified human anti-gM/gN antibodies reacted specifically by
      immunofluorescence with HCMV-infected human fibroblasts and with cells
      transiently expressing gM/gN, but not with cells transfected with plasmids
      encoding other immunogenic HCMV proteins. The anti-gM/gN antibodies also reacted
      specifically only with gM/gN in immunoblot assays using lysates of transfected
      cells expressing specific HCMV proteins. Last, human anti-gM/gN antibodies
      efficiently neutralized infectious HCMV in vitro with a capacity comparable to
      that of human anti-gB antibodies. These data indicated that gM/gN can elicit a
      virus-neutralizing antibody response in humans infected with HCMV and therefore
      should be considered a potential candidate for inclusion in prophylactic CMV
      vaccines.

PMID- 16611920
TI  - Linkage of reduced receptor affinity and superinfection to pathogenesis of TR1.3
      murine leukemia virus.
AB  - TR1.3 is a Friend murine leukemia virus (MLV) that induces selective syncytium
      induction (SI) of brain capillary endothelial cells (BCEC), intracerebral
      hemorrhage, and death. Syncytium induction by TR1.3 has been mapped to a single
      tryptophan-to-glycine conversion at position 102 of the envelope glycoprotein
      (Env102). The mechanism of SI by TR1.3 was examined here in comparison to the non
      syncytium-inducing, nonpathogenic MLV FB29, which displays an identical BCEC
      tropism. Envelope protein expression and stability on both infected cells and
      viral particles were not statistically different for TR1.3 and FB29. However,
      affinity measurements derived using purified envelope receptor binding domain
      (RBD) revealed a reduction of >1 log in the K(D) of TR1.3 RBD relative to FB29
      RBD. Whole-virus particles pseudotyped with TR1.3 Env similarly displayed a
      markedly reduced binding avidity compared to FB29-pseudotyped viral particles.
      Lastly, decreased receptor affinity of TR1.3 Env correlated with the failure to
      block superinfection following acute and chronic infection by TR1.3. These
      results definitively show that acquisition of a SI phenotype can be directly
      linked to amino acid changes in retroviral Env that decrease receptor affinity,
      thereby emphasizing the importance of events downstream of receptor binding in
      the cell fusion process and pathology.

PMID- 16611921
TI  - Mouse polyomavirus enters early endosomes, requires their acidic pH for
      productive infection, and meets transferrin cargo in Rab11-positive endosomes.
AB  - Mouse polyomavirus (PyV) virions enter cells by internalization into smooth
      monopinocytic vesicles, which fuse under the cell membrane with larger endosomes.
      Caveolin-1 was detected on monopinocytic vesicles carrying PyV particles in mouse
      fibroblasts and epithelial cells (33). Here, we show that PyV can be efficiently
      internalized by Jurkat cells, which do not express caveolin-1 and lack caveolae,
      and that overexpression of a caveolin-1 dominant-negative mutant in mouse
      epithelial cells does not prevent their productive infection. Strong
      colocalization of VP1 with early endosome antigen 1 (EEA1) and of EEA1 with
      caveolin-1 in mouse fibroblasts and epithelial cells suggests that the
      monopinocytic vesicles carrying the virus (and vesicles containing caveolin-1)
      fuse with EEA1-positive early endosomes. In contrast to SV40, PyV infection is
      dependent on the acidic pH of endosomes. Bafilomycin A1 abolished PyV infection,
      and an increase in endosomal pH by NH4Cl markedly reduced its efficiency when
      drugs were applied during virion transport towards the cell nucleus. The block of
      acidification resulted in the retention of a fraction of virions in early
      endosomes. To monitor further trafficking of PyV, we used fluorescent resonance
      energy transfer (FRET) to determine mutual localization of PyV VP1 with
      transferrin and Rab11 GTPase at a 2- to 10-nm resolution. Positive FRET between
      PyV VP1 and transferrin cargo and between PyV VP1 and Rab11 suggests that during
      later times postinfection (1.5 to 3 h), the virus meets up with transferrin in
      the Rab11-positive recycling endosome. These results point to a convergence of
      the virus and the cargo internalized by different pathways in common transitional
      compartments.

PMID- 16611922
TI  - Regulated cleavages at the West Nile virus NS4A-2K-NS4B junctions play a major
      role in rearranging cytoplasmic membranes and Golgi trafficking of the NS4A
      protein.
AB  - A common feature associated with the replication of most RNA viruses is the
      formation of a unique membrane environment encapsulating the viral replication
      complex. For their part, flaviviruses are no exception, whereupon infection
      causes a dramatic rearrangement and induction of unique membrane structures
      within the cytoplasm of infected cells. These virus-induced membranes, termed
      paracrystalline arrays, convoluted membranes, and vesicle packets, all appear to
      have specific functions during replication and are derived from different
      organelles within the host cell. The aim of this study was to identify which
      protein(s) specified by the Australian strain of West Nile virus, Kunjin virus
      (KUNV), are responsible for the dramatic membrane alterations observed during
      infection. Thus, we have shown using immunolabeling of ultrathin cryosections of
      transfected cells that expression of the KUNV polyprotein intermediates NS4A-4B
      and NS2B-3-4A, as well as that of individual NS4A proteins with and without the C
      terminal transmembrane domain 2K, resulted in different degrees of rearrangement
      of cytoplasmic membranes. The formation of the membrane structures characteristic
      for virus infection required coexpression of an NS4A-NS4B cassette with the viral
      protease NS2B-3pro which was shown to be essential for the release of the
      individual NS4A and NS4B proteins. Individual expression of NS4A protein
      retaining the C-terminal transmembrane domain 2K resulted in the induction of
      membrane rearrangements most resembling virus-induced structures, while removal
      of the 2K domain led to a less profound membrane rearrangement but resulted in
      the redistribution of the NS4A protein to the Golgi apparatus. The results show
      that cleavage of the KUNV polyprotein NS4A-4B by the viral protease is the key
      initiation event in the induction of membrane rearrangement and that the NS4A
      protein intermediate containing the uncleaved C-terminal transmembrane domain
      plays an essential role in these membrane rearrangements.

PMID- 16611923
TI  - Generation of infectious hepatitis C virus in immortalized human hepatocytes.
AB  - Progress in understanding hepatitis C virus (HCV) biology has remained a
      challenge due to the lack of an efficient cell culture system for virus growth.
      In this study, we examined HCV core protein-mediated immortalized human
      hepatocytes (IHH) for growth of HCV. In vitro-transcribed full-length RNA from
      HCV genotype 1a (clone H77) was introduced into IHH by electroporation. Reverse
      transcription-PCR of cellular RNA isolated from HCV genome-transfected IHH
      suggested that viral RNA replication occurred. IHH transfected with the full
      length HCV genome also displayed viral protein expression by indirect
      immunofluorescence. In contrast, cells transfected with polymerase-defective HCV
      (H77/GND) RNA as a negative control did not exhibit expression of the viral
      genome. Immunogold labeling demonstrated localization of E1 protein in the rough
      endoplasmic reticulum of RNA-transfected IHH. Virus-like particles of
      approximately 50 nm were observed in the cytoplasm. After being inoculated with
      culture media of cells transfected with the full-length HCV genome, naive IHH
      displayed NS5a protein expression in a dilution-dependent manner, but expression
      of NS5a was inhibited by prior incubation of culture medium with HCV-infected
      patient sera. NS5a-positive immunofluorescence of cell culture media of IHH
      transfected with full-length H77 RNA yielded approximately 4.5 x 10(4) to 1 x
      10(5) focus-forming units/ml. A similar level of virus growth was observed upon
      transfection of RNA from HCV genotype 2a (JFH1) into IHH. Taken together, our
      results suggest that IHH support HCV genome replication and virus assembly.

PMID- 16611924
TI  - Newly identified families of human endogenous retroviruses.

PMID- 16611925
TI  - Early fibropapillomas in Hawaii and occurrences in all sea turtle species: the
      panzootic, associated leeches wide-ranging on sea turtles, and species of study
      leeches should be identified.

PMID- 16611926
TI  - Teachers' perceptions of and responses to adolescents with chronic pain
      syndromes.
AB  - OBJECTIVE: To examine factors that influence teachers' perceptions of and
      responses to chronic pain in students. METHODS: Two-hundred and sixty classroom
      teachers responded to a vignette describing a student with limb pain. The 2 x 2 x
      2 factorial design included conditions that varied by (a) the presence or absence
      of documented organic evidence for the pain, (b) cooperative vs. confrontational
      parent-teacher interactions, and (c) the presence or absence of communication
      from the medical team. Teachers rated pain severity and impairment, relief from
      classroom responsibilities, extent of accommodations the student would require in
      school, and sympathy for the student and family. RESULTS: Documented medical
      evidence supporting the pain was the most influential factor affecting teachers'
      responses to pain. Parental attitude also influenced responses. Communication
      from the medical team influenced teachers' decisions about relief from
      responsibilities but did not affect other reactions. CONCLUSIONS: Teachers'
      responses to students with pain are influenced by situational factors. Efforts to
      increase school functioning in youth with chronic pain should incorporate
      attempts to help teachers respond to pain adaptively.

PMID- 16611927
TI  - Small protein B interacts with the large and the small subunits of a stalled
      ribosome during trans-translation.
AB  - During trans-translation, stalled bacterial ribosomes are rescued by small
      protein B (SmpB) and by transfer-messenger RNA (tmRNA). Stalled ribosomes switch
      translation from the defective messages to a short internal reading frame on
      tmRNA that tags the nascent peptide chain for degradation and recycles the
      ribosomes. We present evidences that SmpB binds the large and small ribosomal
      subunits in vivo and in vitro. The binding between SmpB and the ribosomal
      subunits is very tight, with a dissociation constant of 1.7 x 10(-10) M, similar
      to its K(D) for the 70S ribosome or for tmRNA. tmRNA displaces SmpB from its 50S
      binding but not from the 30S. In vivo, SmpB is detected on the 50S when trans
      translation is impaired by lacking tmRNA or a functional SmpB. SmpB contacts the
      large subunit transiently and early during the trans-translational process. The
      affinity of SmpB for the two ribosomal subunits is modulated by tmRNA in the
      course of trans-translation. It is the first example of two copies of the same
      protein interacting with two different functional sites of the ribosomes.

PMID- 16611928
TI  - West Nile virus in the United States (1999-2005).
AB  - The accidental introduction of West Nile Virus into New York City from the Old
      World in 1999 resulted in an epidemic in humans, horses, and birds that swept to
      the west coast in just 3 years. The virus is transmitted by infective mosquitoes
      among susceptible native birds, which serve as amplifying hosts. Clinical disease
      occurs in humans and horses, but not enough virus is produced in their blood to
      infect other mosquitoes; therefore, humans and horses are considered dead-end
      hosts. Humans can best protect themselves by remaining indoors during periods of
      high mosquito activity and/or by using recommended repellents. Effective vaccines
      are available for horses.

PMID- 16611929
TI  - Efficacy and safety of preoperative etodolac and butorphanol administration in
      dogs undergoing ovariohysterectomy.
AB  - Eighteen dogs undergoing ovariohysterectomy were premedicated with etodolac,
      butorphanol, or their combination. Various parameters, such as blood pressure,
      isoflurane requirements, behavioral pain scores, plasma cortisol concentration,
      plasma glucose concentration, and mucosal bleeding time, were assessed. The
      integrated plasma cortisol values were significantly lower in the etodolac and
      etodolac with butorphanol groups. Dogs receiving etodolac and butorphanol had the
      lowest behavioral pain scores from extubation until the end of monitoring.
      Isoflurane concentration over time (area under the curve), buccal mucosal
      bleeding time, and indices of renal function were not significantly different
      among the treatment groups.

PMID- 16611930
TI  - Pemphigus foliaceus in 91 dogs.
AB  - A retrospective study of 91 dogs with pemphigus foliaceus was performed. Clinical
      signs of the disease included crusts (n=79), pustules (n=36), and alopecia
      (n=33). Lesions were most common on the trunk (n=53), inner pinnae (n=46), face
      (n=37), and foot pads (n=32). Cytological evaluation revealed acantholytic
      keratinocytes in 37 of 48 dogs. Results of combination treatment with
      prednisolone and azathioprine were comparable to results with prednisolone
      therapy alone. More than half of the dogs achieved remission with appropriate
      therapy, and another 25% significantly improved.

PMID- 16611931
TI  - Complications and outcomes of one-step low-profile gastrostomy devices for long
      term enteral feeding in dogs and cats.
AB  - Sixteen dogs and cats with a variety of primary diseases were retrospectively
      evaluated following endoscopic placement of a one-step low-profile gastrostomy
      device. Overall, the devices were well tolerated, with most complications being
      minor in nature. Complications included bloody or purulent peristomal discharge,
      peristomal swelling, peristomal inflammation, discomfort associated with the
      device, leaking through the device, chewing at the device, premature removal of
      the device, peritonitis, and aspiration pneumonia. Dogs survived for up to 2241
      days, and cats survived for up to 593 days after initial device placement. The
      median survival time after device insertion for dogs was 89 days, and for cats it
      was 87 days.

PMID- 16611932
TI  - Effects of the application of neck pressure by a collar or harness on intraocular
      pressure in dogs.
AB  - The effect on intraocular pressure (IOP) from dogs pulling against a collar or a
      harness was evaluated in 51 eyes of 26 dogs. The force each dog generated while
      pulling against a collar or a harness was measured. Intraocular pressure
      measurements were obtained during application of corresponding pressures via
      collars or harnesses. Intraocular pressure increased significantly from baseline
      when pressure was applied via a collar but not via a harness. Based on the
      results of the study, dogs with weak or thin corneas, glaucoma, or conditions for
      which an increase in IOP could be harmful should wear a harness instead of a
      collar, especially during exercise or activity.

PMID- 16611933
TI  - Disposition of deracoxib in cats after oral administration.
AB  - The pharmacokinetics of deracoxib in seven healthy cats were determined following
      a single oral (1 mg/kg) dose. Minimal variability among cats was found for all
      estimated pharmacokinetic variables. Terminal half-life (t(1/2)) was 7.9 hours.
      The mean maximum concentration (C(max)) was 0.28 microg/mL and was measured 3.64
      hours after drug administration. Deracoxib was not detectable in the plasma after
      60 hours. The compounded liquid formula was accepted readily, and no adverse
      effects were observed. Further studies are needed to determine the efficacy and
      safety of deracoxib after acute and chronic use in the cat.

PMID- 16611934
TI  - Surgical revision of the urethral stoma following perineal urethrostomy in 11
      cats: (1998-2004).
AB  - Eleven cats required urethral stoma revision because of urethral stricture
      following perineal urethrostomy. At surgery, eight cats had evidence of
      inadequate dissection to the bulbourethral glands, and three cats had evidence of
      urine extravasation into the subcutaneous tissues. Following revision of the
      stoma, long-term follow-up was obtained in nine cases. For eight cats, owners
      reported no complications after the revision. Failure to dissect beyond the
      bulbourethral glands and inadequate mucosa-to-skin apposition resulted in
      postoperative stricture formation. Stoma revisions were performed a median of 71
      days following the initial perineal urethrostomy, indicating that long-term
      evaluation of cases is necessary.

PMID- 16611935
TI  - Intestinal choristoma in the midcervical region of a dog.
AB  - A 5-year-old, neutered male, mixed-breed dog was evaluated for a fluctuant mass
      in the right midcervical region. The mass recurred following aspiration of its
      contents and after removal of the right sublingual and mandibular salivary
      glands. The lateral midcervical location of the mass and the serous nature of the
      fluid within the mass were inconsistent with a salivary mucocele. Excisional
      biopsy was curative and revealed an intestinal choristoma.

PMID- 16611936
TI  - Fibrocartilaginous embolic myelopathy in five cats.
AB  - Five cats had clinical signs, radiographic findings, and cerebrospinal fluid
      analyses consistent with fibrocartilaginous embolic myelopathy. All cats had an
      acute onset of nonpainful, asymmetrical spinal cord signs (paresis or paralysis
      of one or more limbs). Magnetic resonance imaging was performed in three cats. On
      T2-weighted images, an intramedullary lesion was revealed that was hyperintense
      to normal spinal cord gray matter. On T1-weighted images, the lesion was
      isointense. Three of the cats were euthanized, and postmortem examination
      confirmed myelomalacia with intralesional fibrocartilaginous emboli. Two cats
      survived and were clinically improved within 3 weeks.

PMID- 16611937
TI  - Severe cholestatic liver disease secondary to liver fluke (Platynosomum
      concinnum) infection in three cats.
AB  - Three middle-aged domestic cats were presented for vomiting, lethargy, anorexia,
      and jaundice. Complete blood counts, serum biochemical profiles, and abdominal
      ultrasounds were suggestive of extrahepatic biliary obstruction in all of the
      cats. Infection with the liver fluke Platynosomum concinnum was confirmed by
      intraoperative bile cytology in three cases and by histopathology in two cases.
      All three cats were euthanized in the postoperative period because of
      complications. These cases illustrate the severity of signs and complications
      that can occur with liver fluke infection in cats.

PMID- 16611938
TI  - Survival of a suspected case of central nervous system cuterebrosis in a dog:
      clinical and magnetic resonance imaging findings.
AB  - A 3-year-old, spayed female rat terrier was evaluated for acute onset of stupor,
      disorientation, and tetraparesis. Clinical signs progressed over 3 weeks to
      eventual right-sided hemiparesis and circling to the left. A Cuterebra spp. larva
      was discovered in the vomitus of the dog 2 weeks after the onset of clinical
      signs. Cerebrospinal fluid analysis showed chronic inflammation, and magnetic
      resonance imaging supported a diagnosis of a parasitic tract through the left
      cerebral hemisphere. Medical management included a tapering anti-inflammatory
      dose of prednisone. Clinical signs improved slowly over time. This is the first
      description of a presumptive antemortem diagnosis of canine cuterebrosis in the
      central nervous system.

PMID- 16611939
TI  - Functional replacement of Trypanosoma brucei Argonaute by the human slicer
      Argonaute2.
AB  - RNA interference (RNAi) is widespread throughout the eukaryotic lineage, from
      protozoa to man. Central to all RNAi phenomena is a member of the Argonaute
      protein family, and, in the case of dsRNA-triggered mRNA cleavage, the Ago
      protein functions as the RNAi endonuclease or slicer. However, at present there
      is no definite experimental evidence that slicer Argonautes can be interchanged
      between distantly related organisms. Here, we show that the human slicer
      Argonaute2 (HsAgo2), but not HsAgo1, functions in RNAi in the early divergent
      protozoan Trypanosoma brucei, thus mimicking the situation in mammalian cells.
      This finding indicates that the basic features of the RNAi mechanism are
      conserved from T. brucei to man.

PMID- 16611941
TI  - Induction of the interferon response by siRNA is cell type- and duplex length
      dependent.
AB  - Long (27-29-bp dsRNA) Dicer-dependent substrates have been identified as potent
      mediators of RNAi-induced gene knockdown in HEK293 and HeLa cells. As the lengths
      of these molecules are reported to be below the threshold generally regarded as
      necessary for induction of the mammalian interferon (IFN) response, these long
      siRNA are being considered as RNAi substrates in both research and therapeutic
      settings. In this report, we demonstrate that >23-bp dsRNA can influence cell
      viability and induce a potent IFN response (highlighted by a strong up-regulation
      of the dsRNA receptor, Toll-like receptor 3) in a cell type-specific manner. This
      finding suggests that the length threshold for siRNA induction of the IFN
      response is not fixed but instead varies significantly among different cell
      types. Given the diversity of cell types that comprise whole organisms, these
      findings suggest great care should be taken when considering length variations of
      dsRNA molecules for RNAi experimentation, especially in therapeutic applications.

PMID- 16611940
TI  - Cryptic splice site usage in exon 7 of the human fibrinogen Bbeta-chain gene is
      regulated by a naturally silent SF2/ASF binding site within this exon.
AB  - In this work we report the identification of a strong SF2/ASF binding site within
      exon 7 of the human fibrinogen Bbeta-chain gene (FGB). Its disruption in the wild
      type context has no effect on exon recognition. However, when the mutation IVS7 +
      1G>T--initially described in a patient suffering from congenital afibrinogenemia-
      is present, this SF2/ASF binding site is critical for cryptic 5'ss (splice site)
      definition. These findings, besides confirming and extending previous results
      regarding the effect of SF2/ASF on cryptic splice site activation, identify for
      the first time an enhancer sequence in the FGB gene specific for cryptic splice
      site usage. Taken together, they suggest the existence of a splicing-regulatory
      network that is normally silent in the FGB natural splicing environment but which
      can nonetheless influence splicing decisions when local contexts allow. On a more
      general note, our conclusions have implications for the evolution of alternative
      splicing processes and for the development of methods to control aberrant
      splicing in the context of disease-causing mutations.

PMID- 16611942
TI  - Compositionally and functionally distinct editosomes in Trypanosoma brucei.
AB  - Uridylate insertion/deletion RNA editing in Trypanosoma brucei mitochondria is
      catalyzed by a multiprotein complex, the approximately 20S editosome. Editosomes
      purified via three related tagged RNase III proteins, KREN1 (KREPB1/TbMP90),
      KREPB2 (TbMP67), and KREN2 (KREPB3/TbMP61), had very similar but nonidentical
      protein compositions, and only the tagged member of these three RNase III
      proteins was identified in each respective complex. Three new editosome proteins
      were also identified in these complexes. Each tagged complex catalyzed both
      precleaved insertion and deletion editing in vitro. However, KREN1 complexes
      cleaved deletion but not insertion editing sites in vitro, and, conversely, KREN2
      complexes cleaved insertion but not deletion editing sites. These specific
      nuclease activities were abolished by mutations in the putative RNase III
      catalytic domain of the respective proteins. Thus editosomes appear to be
      heterogeneous in composition with KREN1 complexes catalyzing cleavage of deletion
      sites and KREN2 complexes cleaving insertion sites while both can catalyze the U
      addition, U removal, and ligation steps of editing.

PMID- 16611944
TI  - Videos in Clinical Medicine. Placement of an arterial line.

PMID- 16611943
TI  - The domain of the Bacillus subtilis DEAD-box helicase YxiN that is responsible
      for specific binding of 23S rRNA has an RNA recognition motif fold.
AB  - The YxiN protein of Bacillus subtilis is a member of the DbpA subfamily of
      prokaryotic DEAD-box RNA helicases. Like DbpA, it binds with high affinity and
      specificity to segments of 23S ribosomal RNA as short as 32 nucleotides (nt) that
      include hairpin 92. Several experiments have shown that the 76-residue carboxy
      terminal domain of YxiN is responsible for the high-affinity RNA binding. The
      domain has been crystallized and its structure has been solved to 1.7 Angstroms
      resolution. The structure reveals an RNA recognition motif (RRM) fold that is
      found in many eukaryotic RNA binding proteins; the RRM fold was not apparent from
      the amino acid sequence. The domain has two solvent exposed aromatic residues at
      sites that correspond to the aromatic residues of the ribonucleoprotein (RNP)
      motifs RNP1 and RNP2 that are essential for RNA binding in many RRMs. However,
      mutagenesis of these residues (Tyr404 and Tyr447) to alanine has little effect on
      RNA affinity, suggesting that the YxiN domain binds target RNAs in a manner that
      differs from the binding mode commonly found in many eukaryotic RRMs.

PMID- 16611945
TI  - Images in clinical medicine. Pseudoclubbing.

PMID- 16611946
TI  - After the storm--health care infrastructure in post-Katrina New Orleans.

PMID- 16611947
TI  - Adaptations.

PMID- 16611948
TI  - Access to the scientific literature--a difficult balance.

PMID- 16611949
TI  - Abdominal sacrocolpopexy with Burch colposuspension to reduce urinary stress
      incontinence.
AB  - BACKGROUND: We designed this trial to assess whether the addition of standardized
      Burch colposuspension to abdominal sacrocolpopexy for the treatment of pelvic
      organ prolapse decreases postoperative stress urinary incontinence in women
      without preoperative symptoms of stress incontinence. METHODS: Women who did not
      report symptoms of stress incontinence and who chose to undergo sacrocolpopexy to
      treat prolapse were randomly assigned to concomitant Burch colposuspension or to
      no Burch colposuspension (control) and were evaluated in a blinded fashion three
      months after the surgery. The primary outcomes included measures of stress
      incontinence (symptoms, stress testing, or treatment) and measures of urge
      symptoms. Enrollment was stopped after the first interim analysis because of a
      significantly lower frequency of stress incontinence in the group that underwent
      the Burch colposuspension. RESULTS: Of 322 women who underwent randomization, 157
      were assigned to Burch colposuspension and 165 to the control group. Three months
      after surgery, 33.6 percent of the women in the Burch group and 57.4 percent of
      the controls met one or more of the criteria for stress incontinence (P<0.001)
      [Corrected]. There was no significant difference between the Burch group and the
      control group in the frequency of urge incontinence (32.7 percent vs. 38.4
      percent, P=0.48). After surgery, women in the control group were more likely to
      report bothersome symptoms of stress incontinence than those in the Burch group
      who had stress incontinence (24.5 percent vs. 6.1 percent, P<0.001). CONCLUSIONS:
      In women without stress incontinence who are undergoing abdominal sacrocolpopexy
      for prolapse, Burch colposuspension significantly reduced postoperative symptoms
      of stress incontinence without increasing other lower urinary tract symptoms.

PMID- 16611950
TI  - The effect of telithromycin in acute exacerbations of asthma.
AB  - BACKGROUND: We conducted a double-blind, randomized, placebo-controlled study to
      evaluate the efficacy of telithromycin in patients with acute exacerbations of
      asthma. METHODS: A total of 278 adults with diagnosed asthma were enrolled within
      24 hours after an acute exacerbation of asthma requiring short-term medical care.
      The patients were randomly assigned to receive 10 days of oral treatment with
      telithromycin (at a dose of 800 mg daily) or placebo in addition to usual care.
      Primary efficacy end points were a change from baseline over the treatment period
      in symptoms (as recorded by patients in a diary card) and in the peak expiratory
      flow in the morning at home. The presence of Chlamydophila pneumoniae or
      Mycoplasma pneumoniae was ascertained by serologic analysis, polymerase chain
      reaction, and culture. RESULTS: Of the two prespecified primary outcomes, only
      asthma symptoms showed a significantly greater reduction among patients receiving
      telithromycin than among those receiving placebo. Mean (+/-SD) scores on a test
      of asthma symptoms (on a 7-point scale, with 0 denoting no symptoms and 6
      denoting severe symptoms) were 3.0+/-1.4 at baseline and 1.7+/-1.1 at the end of
      treatment for the telithromycin group and 2.8+/-1.3 at baseline and 2.0+/-1.0 at
      the end of treatment for the placebo group. The mean decrease in symptom scores
      during the treatment period was 1.3 for telithromycin and 1.0 for placebo (mean
      difference, -0.3; 95 percent confidence interval, -0.5 to -0.1; P=0.004). There
      was no significant treatment effect on the other primary outcome measure, a
      change in morning peak expiratory flow. Nausea was more common among patients in
      the telithromycin group than in the placebo group (P=0.01). Although 61 percent
      of patients had evidence of infection with C. pneumoniae, M. pneumoniae, or both,
      there was no relationship between bacteriologic status and the response to asthma
      treatment. CONCLUSIONS: This study provides evidence of the benefit of
      telithromycin in patients with acute exacerbations of asthma; the mechanisms of
      benefit remain unclear. (ClinicalTrials.gov number, NCT00273520.).

PMID- 16611951
TI  - Trans fatty acids and cardiovascular disease.

PMID- 16611952
TI  - Images in clinical medicine. Pellagra-like dermatitis.

PMID- 16611953
TI  - Case records of the Massachusetts General Hospital. Case 11-2006. A 54-year-old
      woman with a mass in the pelvis.

PMID- 16611954
TI  - The vexing problem of hidden incontinence.

PMID- 16611955
TI  - Treating acute asthma with antibiotics--not quite yet.

PMID- 16611957
TI  - A toggle for type 2 diabetes?

PMID- 16611958
TI  - Rescue angioplasty after thrombolysis.

PMID- 16611959
TI  - Intraperitoneal chemotherapy for ovarian cancer.

PMID- 16611960
TI  - Hypothermia for neonates with hypoxic-ischemic encephalopathy.

PMID- 16611961
TI  - Deaths from Clostridium sordellii after medical abortion.

PMID- 16611962
TI  - Estrogens and breast cancer.

PMID- 16611963
TI  - Curing the nursing shortage--the role of compensation.

PMID- 16611964
TI  - Postmortem analysis and retrieval of implantable pacemakers and defibrillators.

PMID- 16611965
TI  - High levels of industrially produced trans fat in popular fast foods.

PMID- 16611966
TI  - The scope of qualitatively derived clinical interventions.

PMID- 16611967
TI  - The meaning of support as narrated by family carers who care for a senior
      relative at home.
AB  - The authors' aim in this study is to illuminate the meaning of support as
      narrated by family members who care for a senior relative at home. This study
      originates from a context of advanced in-home palliative care in Sweden. Twenty
      individuals who cared for a senior relative at home participated. Narrative
      interviews resulted in a text, which the authors analyzed in three recurring
      phases, naive understanding, structural analyses, and comprehensive
      understanding, using a phenomenological hermeneutical method. They formulated two
      themes from the analysis: Experiencing a togetherness with others in caring and
      Sensing togetherness with oneself in caring. The meaning of support was
      understood here as Sensing togetherness. In the comprehensive understanding, the
      authors further illuminate this meaning using literature on the concepts of
      friendship, inner strength, and manageability through the sense of coherence
      theory. They provide suggestions for relevance to practice and further research.

PMID- 16611968
TI  - The specifics of coping: parents of daughters with anorexia nervosa.
AB  - In this article, the authors report on an interview study in which parents
      described the coping strategies they used to deal with the demands of having a
      daughter diagnosed with anorexia nervosa. They compare parents' accounts with
      commonly used categorizations in quantitative studies of parental coping and
      adjustment. The study indicates that parents attribute multiple, complex, and
      unique motives to their actions that problematize quantitative constructions of
      types of coping. Parents often defined their actions differently and reported
      using coping strategies that were not considered or measured by the most widely
      used quantitative coping instruments. The analysis indicates that when the focus
      is on understanding and assisting parental coping in particular circumstances,
      situated, context-specific analyses are necessary to design measures that
      accurately reflect parents' coping efforts.

PMID- 16611969
TI  - Storying disability and impairment: retrospective accounts of disabled family
      life.
AB  - Much previous British research on disability and its effects on family life has
      seen impairment as a personal or family tragedy. In this article, the authors
      describe current English research that is asking families about their experiences
      of professional health and social care support since the birth of their disabled
      child. Interviews with the families uncovered a range of themes that challenged
      the personal tragedy approach. Far from being passive recipients of care, these
      are ordinary families seeking appropriate information from professionals to
      support them in their ordinary parenting role. For them, the professionalized
      care service should be based on negotiated relationships of equality that give
      respect to parental perspectives on what is right for their child. The authors
      conclude that these data are useful in describing ongoing barriers to enabling
      care provision and in offering a positive view of disabled family life.

PMID- 16611970
TI  - Striving for therapeutic relationships: parent-provider communication in the
      developmental treatment setting.
AB  - The purpose of this grounded theory study is to develop a beginning substantive
      theory that explains the communication process between parents of children
      receiving center-based services for developmental delays and disabilities and the
      professional providers of those services. Communication is defined broadly as
      including both content and relationship dimensions. Twenty parents and 14
      providers described their experience of communication with one another. The core
      phenomenon constructed from the data was striving for therapeutic relationships
      within a context of uncertainty. Both parents and providers operated in a context
      of uncertainty regarding the child and his or her development and prospects for
      the future as well as their expectations of each other. Both parents and
      providers used strategies of balancing, reading the cues, questioning, managing
      uncertainty, and managing the sessions. The outcomes were relationships that were
      valued by the extent to which they were perceived as therapeutic to parents and
      child.

PMID- 16611971
TI  - Parental schemata in the management of children with attention deficit
      hyperactivity disorder.
AB  - The authors describe the management schemata held by parents of children
      diagnosed with attention deficit-hyperactivity disorder (ADHD). They conducted
      semistructured interviews with 10 mothers of children who had ADHD and used
      interpretative, phenomenological analysis on the interview transcriptions to
      identify the schemata that guided the parents' management practices. The
      predominant schemata were the perceived difference of children with ADHD,
      parental aspirations, the necessity of medication, psychological management,
      parental authority, role of the father, mothering concept, and community support.
      The authors discuss these schemata in the context of the current controversy as
      to whether ADHDis best regarded as a medical or a developmental disorder. They
      conclude that the parents' schemata conformed to current child-raising theory,
      but as a consequence, the parents might not consider social factors involved in
      the development of ADHD sufficiently. The authors suggest that this restricted
      perspective limits the parents' options for managing the condition.

PMID- 16611972
TI  - Perceived social support and HIV/AIDS medication adherence among African American
      women.
AB  - HIV/AIDS incidence is increasing more quickly among women than any other segment
      of the population. The typical woman with HIV/AIDS is young, in her late 20s,
      economically challenged, and of childbearing age. Adherence to HIV therapies is
      critical if patients are to achieve and maintain virologic suppression. The
      author recruited HIV/AIDS-infected African American women from an outpatient
      clinic to investigate the women's perceptions of social support and how it
      affected their medication adherence. She collected data through tape-recorded
      interviews using a semistructured guide and journaling over a 2-week period.
      Facilitators of adherence included supportive family members and having young
      children. Barriers to adherence included perceived stigma, feeling unloved or
      uncared for, relationship turbulence, and having a husband who was also HIV
      positive. Although participants reported being "fairly" satisfied with the
      quality of support they received, emotional support and often instrumental
      support were most desired and wanted.

PMID- 16611973
TI  - The myth of creating an integrative story: the therapeutic experience of
      Holocaust survivors.
AB  - In this article, the authors explore how Holocaust survivors experience therapy.
      The qualitative method by which the authors illuminate the therapeutic experience
      is in-depth interviews with 11 survivors. They base their analysis on the
      phenomenological tradition and use psychodynamic perspective as a heuristic
      device, generating five main themes: (a) knowing and not knowing the story of the
      trauma, (b) therapy as a reproduction of the trauma and its aftermath, (c) the
      fight to keep the therapist as a split object, (d) the perception of therapy as
      interminable, and (e) creating alternative narratives. Overall, the findings
      contradict the traditional perception, in which the goal of therapy is defined as
      one of integrating the traumatic narrative with the entire life story. Successful
      therapy, as was found in the present study, is often experienced when the
      traumatic narrative is put into a capsule separated from other parts of the life
      story.

PMID- 16611974
TI  - Writing qualitatively, or the demands of writing.
AB  - Have you ever said this or heard someone say this: "I have done all of my data
      analysis--I just have to write it down." Or, "I just have to write it up"? I will
      suggest that within the context of phenomenological inquiry, it is not
      necessarily helpful to try to assist researchers learning "how to write down"
      their reflections or "how to write up" their results. What should be more helpful
      is learning "how to write." Qualitative writing may be seen as an active struggle
      for understanding and recognition of the lived meanings of the lifeworld, and
      this writing also possesses passive and receptive rhetoric dimensions. It
      requires that we be attentive to other voices, to subtle significations in the
      way that things and others speak to us. In part, this is achieved through contact
      with the words of others. These words need to touch us, guide us, stir us.

PMID- 16611975
TI  - The role of rapport: lessons learned from conducting research in a primary care
      setting.
AB  - Conducting research in a primary care setting is difficult because of the
      competing demands primary care offices have to manage in the current medical
      environment. Every primary care office has its own relationship and reporting
      structures, norms, and ways of conducting day-to-day affairs. Regardless of the
      setting, when carrying out qualitative and/or mixed-methods research, researchers
      must have rapport with the individuals or group of individuals they will be
      working with to carry out the research. In this article, the authors describe the
      different approaches that research staff have used to create rapport with
      practice staff that were not only participants in the study but were also
      responsible for the delivery and implementation of this effectiveness study.

PMID- 16611976
TI  - 'GnRH agonist trigger: looking for the coin under the lamp post?'.

PMID- 16611977
TI  - High (feminized) digit ratio (2D : 4D) in Danish men: a question of measurement
      method?

PMID- 16611978
TI  - Choice of ART programme for serodiscordant couples with an HIV infected male
      partner.

PMID- 16611979
TI  - Ubp8p, a histone deubiquitinase whose association with SAGA is mediated by
      Sgf11p, differentially regulates lysine 4 methylation of histone H3 in vivo.
AB  - Despite recent advances in characterizing the regulation of histone H3 lysine 4
      (H3-K4) methylation at the GAL1 gene by the H2B-K123-specific deubiquitinase
      activity of Saccharomyces cerevisiae SAGA (Spt-Ada-Gcn5-acetyltransferase)
      associated Ubp8p, our knowledge on the general role of Ubp8p at the SAGA
      dependent genes is lacking. For this study, using a formaldehyde-based in vivo
      cross-linking and chromatin immunoprecipitation (ChIP) assay, we have analyzed
      the role of Ubp8p in the regulation of H3-K4 methylation at three other SAGA
      dependent yeast genes, namely, PHO84, ADH1, and CUP1. Like that at GAL1, H3-K4
      methylation is increased at the PHO84 core promoter in the UBP8 deletion mutant.
      We also show that H3-K4 methylation remains invariant at the PHO84 open reading
      frame in the Deltaubp8 mutant, demonstrating a highly localized role of Upb8p in
      regulation of H3-K4 methylation at the promoter in vivo. However, unlike that at
      PHO84, H3-K4 methylation at the two other SAGA-dependent genes is not controlled
      by Ubp8p. Interestingly, Ubp8p and H3-K4 methylation are dispensable for
      preinitiation complex assembly at the core promoters of these genes. Our ChIP
      assay further demonstrates that the association of Ubp8p with SAGA is mediated by
      Sgf11p, consistent with recent biochemical data. Collectively, the data show that
      Ubp8p differentially controls H3-K4 methylation at the SAGA-dependent promoters,
      revealing a complex regulatory network of histone methylation in vivo.

PMID- 16611980
TI  - Leaky scanning and reinitiation regulate BACE1 gene expression.
AB  - beta-Site beta-amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is the
      beta-secretase in vivo for processing APP to generate amyloid beta protein
      (Abeta). Abeta deposition in the brain is the hallmark of Alzheimer's disease
      (AD) neuropathology. Inhibition of BACE1 activity has major pharmaceutical
      potential for AD treatment. The expression of the BACE1 gene is relatively low in
      vivo. The control of BACE1 expression has not been well defined. There are six
      upstream AUGs (uAUGs) in the 5' leader sequence of the human BACE1 mRNA. We
      investigated the role of the promoter and the uATGs in the 5' untranslated region
      (UTR) of the human BACE1 gene in BACE1 gene transcription and translation
      initiation. Our results show that the first and second uATGs are the integral
      part of the core minimal promoter of the human BACE1 gene, while the third uAUG
      is skipped over by ribosomal scanning. The fourth uAUG can function as a
      translation initiation codon, and deletion or mutation of this uAUG increases
      downstream gene expression. The fourth uAUG of the BACE1 5'UTR is responsible for
      inhibiting the expression of BACE1. Translation initiation by the BACE1 uAUGs and
      physiological AUG requires intact eIF4G. Our results demonstrate that during
      human BACE1 gene expression, ribosomes skipped some uAUGs by leaky scanning and
      translated an upstream open reading frame, initiated efficiently at the fourth
      uAUG, and subsequently reinitiated BACE1 translation at the physiological AUG
      site. Such leaky scanning and reinitiation resulted in weak expression of BACE1
      under normal conditions. Alterations of the leaky scanning and reinitiation in
      BACE1 gene expression could play an important role in AD pathogenesis.

PMID- 16611981
TI  - Sonic hedgehog signaling regulates Gli2 transcriptional activity by suppressing
      its processing and degradation.
AB  - Gli2 and Gli3 are the primary transcription factors that mediate Sonic hedgehog
      (Shh) signals in the mouse. Gli3 mainly acts as a transcriptional repressor,
      because the majority of full-length Gli3 protein is proteolytically processed.
      Gli2 is mostly regarded as a transcriptional activator, even though it is also
      suggested to have a weak repressing activity. What the molecular basis for its
      possible dual function is and how its activity is regulated by Shh signaling are
      largely unknown. Here we demonstrate that unlike the results seen with Gli3 and
      Cubitus Interruptus, the fly homolog of Gli, only a minor fraction of Gli2 is
      proteolytically processed to form a transcriptional repressor in vivo and that in
      addition to being processed, Gli2 full-length protein is readily degraded. The
      degradation of Gli2 requires the phosphorylation of a cluster of numerous serine
      residues in its carboxyl terminus by protein kinase A and subsequently by casein
      kinase 1 and glycogen synthase kinase 3. The phosphorylated Gli2 interacts
      directly with betaTrCP in the SCF ubiquitin-ligase complex through two binding
      sites, which results in Gli2 ubiquitination and subsequent degradation by the
      proteasome. Both processing and degradation of Gli2 are suppressed by Shh
      signaling in vivo. Our findings provide the first demonstration of a molecular
      mechanism by which the Gli2 transcriptional activity is regulated by Shh
      signaling.

PMID- 16611982
TI  - Cdc37 interacts with the glycine-rich loop of Hsp90 client kinases.
AB  - Recently, we identified a client-binding site of Cdc37 that is required for its
      association with protein kinases. Phage display technology and liquid
      chromatography-tandem mass spectrometry (which identifies a total of 33 proteins)
      consistently identify a unique sequence, GXFG, as a Cdc37-interacting motif that
      occurs in the canonical glycine-rich loop (GXGXXG) of protein kinases, regardless
      of their dependence on Hsp90 or Cdc37. The glycine-rich motif of Raf-1 (GSGSFG)
      is necessary for its association with Cdc37; nevertheless, the N lobe of Raf-1
      (which includes the GSGSFG motif) on its own cannot interact with Cdc37. Chimeric
      mutants of Cdk2 and Cdk4, which differ sharply in their affinities toward Cdc37,
      show that their C-terminal portions may determine this difference. In addition, a
      nonclient kinase, the catalytic subunit of cyclic AMP-dependent protein kinase,
      interacts with Cdc37 but only when a threonine residue in the activation segment
      of its C lobe is unphosphorylated. Thus, although a region in the C termini of
      protein kinases may be crucial for accomplishing and maintaining their
      interaction with Cdc37, we conclude that the N-terminal glycine-rich loop of
      protein kinases is essential for physically associating with Cdc37.

PMID- 16611983
TI  - Role for Upf2p phosphorylation in Saccharomyces cerevisiae nonsense-mediated mRNA
      decay.
AB  - Premature termination (nonsense) codons trigger rapid mRNA decay by the nonsense
      mediated mRNA decay (NMD) pathway. Two conserved proteins essential for NMD, UPF1
      and UPF2, are phosphorylated in higher eukaryotes. The phosphorylation and
      dephosphorylation of UPF1 appear to be crucial for NMD, as blockade of either
      event in Caenorhabditis elegans and mammals largely prevents NMD. The
      universality of this phosphorylation/dephosphorylation cycle pathway has been
      questioned, however, because the well-studied Saccharomyces cerevisiae NMD
      pathway has not been shown to be regulated by phosphorylation. Here, we used in
      vitro and in vivo biochemical techniques to show that both S. cerevisiae Upf1p
      and Upf2p are phosphoproteins. We provide evidence that the phosphorylation of
      the N-terminal region of Upf2p is crucial for its interaction with Hrp1p, an RNA
      binding protein that we previously showed is essential for NMD. We identify
      specific amino acids in Upf2p's N-terminal domain, including phosphorylated
      serines, which dictate both its interaction with Hrp1p and its ability to elicit
      NMD. Our results indicate that phosphorylation of UPF1 and UPF2 is a conserved
      event in eukaryotes and for the first time provide evidence that Upf2p
      phosphorylation is crucial for NMD.

PMID- 16611984
TI  - The negative c-Myc target onzin affects proliferation and apoptosis via its
      obligate interaction with phospholipid scramblase 1.
AB  - Onzin, the product of a negatively c-Myc-regulated target gene, is highly
      expressed in myeloid cells. As a result of its interaction with and activation of
      Akt1 and Mdm2, onzin down-regulates p53. The apoptotic sensitivity of several
      cell lines is thus directly related to onzin levels. We have conducted a search
      for additional onzin-interacting proteins and identified phospholipid scramblase
      1 (PLSCR1), an endofacial membrane protein, which is proposed to mediate the
      bidirectional movement of plasma membrane phospholipids during proliferation and
      apoptosis. PLSCR1 interacts with the same cysteine-rich domain of onzin as do
      Akt1 and Mdm2, whereas the onzin-interacting domain of PLSCR1 centers around, but
      does not require, a previously identified palmitoylation signal. Depletion of
      endogenous PLSCR1 in myeloid cells leads to a phenotype that mimics that of onzin
      overexpression, providing evidence that PLSCR1 is a physiologic regulator of
      onzin. In contrast, PLSCR1 overexpression in fibroblasts, which normally do not
      express onzin, affects neither growth nor apoptosis unless onzin is coexpressed,
      in which case PLSCR1 completely abrogates onzin's positive effects on
      proliferation and survival. These findings demonstrate a functional
      interdependence between onzin and PLSCR1. They further suggest a contiguous link
      between the earliest events mediated by c-Myc and the latest ones, which
      culminate at the cell surface and lead to phospholipid reshuffling and cell
      death.

PMID- 16611985
TI  - Protein kinase C delta activates topoisomerase IIalpha to induce apoptotic cell
      death in response to DNA damage.
AB  - DNA topoisomerase II is an essential nuclear enzyme that modulates DNA processes
      by altering the topological state of double-stranded DNA. This enzyme is required
      for chromosome condensation and segregation; however, the regulatory mechanism of
      its activation is largely unknown. Here we demonstrate that topoisomerase IIalpha
      is activated in response to genotoxic stress. Concomitant with the activation,
      the expression of topoisomerase IIalpha is increased following DNA damage. The
      results also demonstrate that the proapoptotic kinase protein kinase C delta
      (PKCdelta) interacts with topoisomerase IIalpha. This association is in an S
      phase-specific manner and is required for stabilization and catalytic activation
      of topoisomerase IIalpha in response to DNA damage. Conversely, inhibition of
      PKCdelta activity attenuates DNA damage-induced activation of topoisomerase
      IIalpha. Finally, aberrant activation of topoisomerase IIalpha by PKCdelta is
      associated with induction of apoptosis upon exposure to genotoxic agents. These
      findings indicate that PKCdelta regulates topoisomerase IIalpha and thereby cell
      fate in the genotoxic stress response.

PMID- 16611986
TI  - Cooperative regulation of extracellular signal-regulated kinase activation and
      cell shape change by filamin A and beta-arrestins.
AB  - beta-Arrestins (betaarr) are multifunctional adaptor proteins that can act as
      scaffolds for G protein-coupled receptor activation of mitogen-activated protein
      kinases (MAPK). Here, we identify the actin-binding and scaffolding protein
      filamin A (FLNA) as a betaarr-binding partner using Son of sevenless recruitment
      system screening, a classical yeast two-hybrid system, coimmunoprecipitation
      analyses, and direct binding in vitro. In FLNA, the betaarr-binding site involves
      tandem repeat 22 in the carboxyl terminus. betaarr binds FLNA through both its N-
      and C-terminal domains, indicating the presence of multiple binding sites. We
      demonstrate that betaarr and FLNA act cooperatively to activate the MAPK
      extracellular signal-regulated kinase (ERK) downstream of activated muscarinic M1
      (M1MR) and angiotensin II type 1a (AT1AR) receptors and provide experimental
      evidence indicating that this phenomenon is due to the facilitation of betaarr
      ERK2 complex formation by FLNA. In Hep2 cells, stimulation of M1MR or AT1AR
      results in the colocalization of receptor, betaarr, FLNA, and active ERK in
      membrane ruffles. Reduction of endogenous levels of betaarr or FLNA and a
      catalytically inactive dominant negative MEK1, which prevents ERK activation,
      inhibit membrane ruffle formation, indicating the functional requirement for
      betaarr, FLNA, and active ERK in this process. Our results indicate that betaarr
      and FLNA cooperate to regulate ERK activation and actin cytoskeleton
      reorganization.

PMID- 16611987
TI  - The tailless nuclear receptor acts as a dedicated repressor in the early
      Drosophila embryo.
AB  - Tailless is an orphan nuclear receptor that controls terminal body patterning in
      Drosophila. Genetic analyses have revealed both positive and negative regulatory
      interactions of Tailless with various target genes, leading to the idea that,
      like many other nuclear receptors, Tailless mediates both activation and
      repression of transcription. In this paper, we have examined the consequences of
      converting Tailless into an obligate repressor and compared the activities of the
      resulting protein with those of wild-type Tailless. We find that this repressor
      form of Tailless behaves like the intact protein in gain- and loss-of-function
      experiments, being sufficient to support normal embryonic development and
      establish accurate patterns of gene expression even for positive Tailless targets
      such as hunchback and brachyenteron. This suggests that Tailless functions
      exclusively as a transcriptional repressor in the embryo and that the observed
      positive interactions of Tailless with specific targets are secondary effects
      involving repression of repressors. We provide evidence that knirps is one such
      repressor gene acting between Tailless and its indirect positive targets.
      Finally, our results indicate that Tailless exerts an active mechanism of
      repression via its ligand-binding domain and that this activity is largely
      independent of the activation function 2 (AF2) motif characteristic of most
      nuclear receptors.

PMID- 16611988
TI  - FATP1 is an insulin-sensitive fatty acid transporter involved in diet-induced
      obesity.
AB  - Fatty acid transport protein 1 (FATP1), a member of the FATP/Slc27 protein
      family, enhances the cellular uptake of long-chain fatty acids (LCFAs) and is
      expressed in several insulin-sensitive tissues. In adipocytes and skeletal
      muscle, FATP1 translocates from an intracellular compartment to the plasma
      membrane in response to insulin. Here we show that insulin-stimulated fatty acid
      uptake is completely abolished in FATP1-null adipocytes and greatly reduced in
      skeletal muscle of FATP1-knockout animals while basal LCFA uptake by both tissues
      was unaffected. Moreover, loss of FATP1 function altered regulation of
      postprandial serum LCFA, causing a redistribution of lipids from adipocyte tissue
      and muscle to the liver, and led to a complete protection from diet-induced
      obesity and insulin desensitization. This is the first in vivo evidence that
      insulin can regulate the uptake of LCFA by tissues via FATP1 activation and that
      FATPs determine the tissue distribution of dietary lipids. The strong protection
      against diet-induced obesity and insulin desensitization observed in FATP1-null
      animals suggests FATP1 as a novel antidiabetic target.

PMID- 16611989
TI  - Specific role of the SR protein splicing factor B52 in cell cycle control in
      Drosophila.
AB  - E2F and retinoblastoma tumor suppressor protein pRB are important regulators of
      cell proliferation; however, the regulation of these proteins in vivo is not well
      understood. In Drosophila there are two E2F genes, an activator, de2f1, and a
      repressor, de2f2. The loss of de2f1 gives rise to the G(1)/S block accompanied by
      the repression of E2F-dependent transcription. These defects can be suppressed by
      mutation of de2f2. In this work, we show that the de2f1 mutant phenotype is
      rescued by the loss of the pre-mRNA splicing factor SR protein B52. Mutations in
      B52 restore S phase in clones of de2f1 mutant cells and phenocopy the loss of the
      de2f2 function. B52 acts upstream of de2f2 and plays a specific role in
      regulation of de2f2 pre-mRNA splicing. In B52-deficient cells, the level of dE2F2
      protein is severely reduced and the expression of dE2F2-dependent genes is
      deregulated. Reexpression of the intronless copy of dE2F2 in B52-deficient cells
      restores the dE2F2-mediated repression. These results uncover a previously
      unrecognized role of the splicing factor in maintaining the G(1)/S block in vivo
      by specific regulation of the dE2F2 repressor function.

PMID- 16611990
TI  - Nucleocytoplasmic trafficking of the Syk protein tyrosine kinase.
AB  - The protein tyrosine kinase Syk couples the B-cell receptor (BCR) for antigen to
      multiple intracellular signaling pathways and also modulates cellular responses
      to inducers of oxidative stress in a receptor-independent fashion. In B cells,
      Syk is found in both the nuclear and cytoplasmic compartments but contains no
      recognizable nuclear localization or export signals. Through the analysis of a
      series of deletion mutants, we identified the presence of an unconventional
      shuttling sequence near the junction of the catalytic domain and the linker B
      region that accounts for Syk's subcellular localization. This localization is
      altered following prolonged engagement of the BCR, which causes Syk to be
      excluded from the nucleus. Nuclear exclusion requires the receptor-mediated
      activation of protein kinase C and new protein synthesis. Both of these processes
      also potentiate the activation of caspase 3 in cells in response to oxidative
      stress in a manner that is dependent on the localization of Syk outside of the
      nucleus. In contrast, restriction of Syk to the nucleus greatly diminishes the
      stress-induced activation of caspase 3.

PMID- 16611991
TI  - Genome-wide analysis of p53 under hypoxic conditions.
AB  - Hypoxia is an important nongenotoxic stress that modulates the tumor suppressor
      activity of p53 during malignant progression. In this study, we investigated how
      genotoxic and nongenotoxic stresses regulate p53 association with chromatin, p53
      transcriptional activity, and p53-dependent apoptosis. We found that genotoxic
      and nongenotoxic stresses result in the accumulation and binding of the p53 tumor
      suppressor protein to the same cognate binding sites in chromatin. However, it is
      the stress that determines whether downstream signaling is mediated by
      association with transcriptional coactivators. In contrast to p53 induced by DNA
      damaging agents, hypoxia-induced p53 has primarily transrepression activity.
      Using extensive microarray analysis, we identified families of repressed targets
      of p53 that are involved in cell signaling, DNA repair, cell cycle control, and
      differentiation. Following our previous study on the contribution of residues 25
      and 26 to p53-dependent hypoxia-induced apoptosis, we found that residues 25-26
      and 53-54 and the polyproline- and DNA-binding regions are also required for both
      gene repression and the induction of apoptosis by p53 during hypoxia. This study
      defines a new role for residues 53 and 54 of p53 in regulating transrepression
      and demonstrates that 25-26 and 53-54 work in the same pathway to induce
      apoptosis through gene repression.

PMID- 16611992
TI  - Competitive control of independent programs of tumor necrosis factor receptor
      induced cell death by TRADD and RIP1.
AB  - Stimulation of tumor necrosis factor receptor 1 (TNFR1) can initiate several
      cellular responses, including apoptosis, which relies on caspases, necrotic cell
      death, which depends on receptor-interacting protein kinase 1 (RIP1), and NF
      kappaB activation, which induces survival and inflammatory responses. The TNFR
      associated death domain (TRADD) protein has been suggested to be a crucial signal
      adaptor that mediates all intracellular responses from TNFR1. However, cells with
      a genetic deficiency of TRADD are unavailable, precluding analysis with mature
      immune cell types. We circumvented this problem by silencing TRADD expression
      with small interfering RNA. We found that TRADD is required for TNFR1 to induce
      NF-kappaB activation and caspase-8-dependent apoptosis but is dispensable for
      TNFR1-initiated, RIP1-dependent necrosis. Our data also show that TRADD and RIP1
      compete for recruitment to the TNFR1 signaling complex and the distinct programs
      of cell death. Thus, TNFR1-initiated intracellular signals diverge at a very
      proximal level by the independent association of two death domain-containing
      proteins, RIP1 and TRADD. These single transducers determine cell fate by
      triggering NF-kappaB activation, apoptosis, and nonapoptotic death signals
      through separate and competing signaling pathways.

PMID- 16611993
TI  - Differential regulation of the transcriptional activities of hypoxia-inducible
      factor 1 alpha (HIF-1alpha) and HIF-2alpha in stem cells.
AB  - Transcriptional responses to hypoxia are primarily mediated by hypoxia-inducible
      factors (HIFs), HIF-1alpha and HIF-2alpha. The HIF-1alpha and HIF-2alpha subunits
      are structurally similar in their DNA binding and dimerization domains but differ
      in their transactivation domains, implying they may have unique target genes and
      require distinct transcriptional cofactors. Our previous results demonstrated
      that HIF-1alpha and HIF-2alpha regulate distinct target genes. Here, we report
      that HIF-2alpha is not transcriptionally active in embryonic stem (ES) cells, as
      well as possible inhibition by a HIF-2alpha-specific transcriptional repressor.
      Using DNA microarray analysis of hypoxia-inducible genes in wild-type (WT), Hif
      1alpha(-)(/)(-), and Hif-2alpha(-)(/)(-) ES cells, we show that HIF-1alpha
      induces a large number of both confirmed and novel hypoxia-inducible genes, while
      HIF-2alpha does not activate any of its previously described targets. We further
      demonstrate that inhibition of HIF-2alpha function occurs at the level of
      transcription cofactor recruitment to endogenous target gene promoters.
      Overexpression of WT and, notably, a DNA-binding-defective HIF-2alpha mutant
      restores endogenous HIF-2alpha protein activity, suggesting that ES cells express
      a HIF-2alpha-specific corepressor that can be titrated by overexpressed HIF
      2alpha protein. HIF-2alpha repression may explain why patients with mutations in
      the VHL tumor suppressor gene display cancerous lesions in specific tissue types.

PMID- 16611994
TI  - Rad18 regulates DNA polymerase kappa and is required for recovery from S-phase
      checkpoint-mediated arrest.
AB  - We have investigated mechanisms that recruit the translesion synthesis (TLS) DNA
      polymerase Polkappa to stalled replication forks. The DNA polymerase processivity
      factor PCNA is monoubiquitinated and interacts with Polkappa in cells treated
      with the bulky adduct-forming genotoxin benzo[a]pyrene dihydrodiol epoxide
      (BPDE). A monoubiquitination-defective mutant form of PCNA fails to interact with
      Polkappa. Small interfering RNA-mediated downregulation of the E3 ligase Rad18
      inhibits BPDE-induced PCNA ubiquitination and association between PCNA and
      Polkappa. Conversely, overexpressed Rad18 induces PCNA ubiquitination and
      association between PCNA and Polkappa in a DNA damage-independent manner.
      Therefore, association of Polkappa with PCNA is regulated by Rad18-mediated PCNA
      ubiquitination. Cells from Rad18(-/-) transgenic mice show defective recovery
      from BPDE-induced S-phase checkpoints. In Rad18(-/-) cells, BPDE induces elevated
      and persistent activation of checkpoint kinases, indicating persistently stalled
      forks due to defective TLS. Rad18-deficient cells show reduced viability after
      BPDE challenge compared with wild-type cells (but survival after hydroxyurea or
      ionizing radiation treatment is unaffected by Rad18 deficiency). Inhibition of
      RPA/ATR/Chk1-mediated S-phase checkpoint signaling partially inhibited BPDE
      induced PCNA ubiquitination and prevented interactions between PCNA and Polkappa.
      Taken together, our results indicate that ATR/Chk1 signaling is required for
      Rad18-mediated PCNA monoubiquitination. Recruitment of Polkappa to ubiquitinated
      PCNA enables lesion bypass and eliminates stalled forks, thereby attenuating the
      S-phase checkpoint.

PMID- 16611995
TI  - The murine ortholog of notchless, a direct regulator of the notch pathway in
      Drosophila melanogaster, is essential for survival of inner cell mass cells.
AB  - Notch signaling is an evolutionarily conserved pathway involved in intercellular
      communication and is essential for proper cell fate choices. Numerous genes
      participate in the modulation of the Notch signaling pathway activity. Among
      them, Notchless (Nle) is a direct regulator of the Notch activity identified in
      Drosophila melanogaster. Here, we characterized the murine ortholog of Nle and
      demonstrated that it has conserved the ability to modulate Notch signaling. We
      also generated mice deficient for mouse Nle (mNle) and showed that its disruption
      resulted in embryonic lethality shortly after implantation. In late mNle(-/-)
      blastocysts, inner cell mass (ICM) cells died through a caspase 3-dependent
      apoptotic process. Most deficient embryos exhibited a delay in the temporal down
      regulation of Oct4 expression in the trophectoderm (TE). However, mNle-deficient
      TE was able to induce decidual swelling in vivo and properly differentiated in
      vitro. Hence, our results indicate that mNle is mainly required in ICM cells,
      being instrumental for their survival, and raise the possibility that the death
      of mNle-deficient embryos might result from abnormal Notch signaling during the
      first steps of development.

PMID- 16611996
TI  - Neuroprotection by histone deacetylase-related protein.
AB  - The expression of histone deacetylase-related protein (HDRP) is reduced in
      neurons undergoing apoptosis. Forced reduction of HDRP expression in healthy
      neurons by treatment with antisense oligonucleotides also induces cell death.
      Likewise, neurons cultured from mice lacking HDRP are more vulnerable to cell
      death. Adenovirally mediated expression of HDRP prevents neuronal death, showing
      that HDRP is a neuroprotective protein. Neuroprotection by forced expression of
      HDRP is not accompanied by activation of the phosphatidylinositol 3-kinase-Akt or
      Raf-MEK-ERK signaling pathway, and treatment with pharmacological inhibitors of
      these pathways fails to inhibit the neuroprotection by HDRP. Stimulation of c-Jun
      phosphorylation and expression, an essential feature of neuronal death, is
      prevented by HDRP. We found that HDRP associates with c-Jun N-terminal kinase
      (JNK) and inhibits its activity, thus explaining the inhibition of c-Jun
      phosphorylation by HDRP. HDRP also interacts with histone deacetylase 1 (HDAC1)
      and recruits it to the c-Jun gene promoter, resulting in an inhibition of histone
      H3 acetylation at the c-Jun promoter. Although HDRP lacks intrinsic deacetylase
      activity, treatment with pharmacological inhibitors of histone deacetylases
      induces apoptosis even in the presence of ectopically expressed HDRP,
      underscoring the importance of c-Jun promoter deacetylation by HDRP-HDAC1 in HDRP
      mediated neuroprotection. Our results suggest that neuroprotection by HDRP is
      mediated by the inhibition of c-Jun through its interaction with JNK and HDAC1.

PMID- 16611997
TI  - Essential dosage-dependent functions of the transcription factor yin yang 1 in
      late embryonic development and cell cycle progression.
AB  - Constitutive ablation of the Yin Yang 1 (YY1) transcription factor in mice
      results in peri-implantation lethality. In this study, we used homologous
      recombination to generate knockout mice carrying yy1 alleles expressing various
      amounts of YY1. Phenotypic analysis of yy1 mutant embryos expressing
      approximately 75%, approximately 50%, and approximately 25% of the normal
      complement of YY1 identified a dosage-dependent requirement for YY1 during late
      embryogenesis. Indeed, reduction of YY1 levels impairs embryonic growth and
      viability in a dose-dependent manner. Analysis of the corresponding mouse
      embryonic fibroblast cells also revealed a tight correlation between YY1 dosage
      and cell proliferation, with a complete ablation of YY1 inducing cytokinesis
      failure and cell cycle arrest. Consistently, RNA interference-mediated inhibition
      of YY1 in HeLa cells prevents cytokinesis, causes proliferative arrest, and
      increases cellular sensitivity to various apoptotic agents. Genome-wide
      expression profiling identified a plethora of YY1 target genes that have been
      implicated in cell growth, proliferation, cytokinesis, apoptosis, development,
      and differentiation, suggesting that YY1 coordinates multiple essential
      biological processes through a complex transcriptional network. These data not
      only shed new light on the molecular basis for YY1 developmental roles and
      cellular functions, but also provide insight into the general mechanisms
      controlling eukaryotic cell proliferation, apoptosis, and differentiation.

PMID- 16611998
TI  - Transforming growth factor beta induces rosettes of podosomes in primary aortic
      endothelial cells.
AB  - Cytoskeletal rearrangements are central to endothelial cell physiology and are
      controlled by soluble factors, matrix proteins, cell-cell interactions, and
      mechanical forces. We previously reported that aortic endothelial cells can
      rearrange their cytoskeletons into complex actin-based structures called
      podosomes when a constitutively active mutant of Cdc42 is expressed. We now
      report that transforming growth factor beta (TGF-beta) promotes podosome
      formation in primary aortic endothelial cells. TGF-beta-induced podosomes
      assembled together into large ring- or crescent-shaped structures. Their
      formation was dependent on protein synthesis and required functional Src,
      phosphatidylinositide 3-kinase, Cdc42, RhoA, and Smad signaling. MT1-MMP and
      metalloprotease 9 (MMP9), both upregulated by TGF-beta, were detected at sites of
      podosome formation, and MT1-MMP was found to be involved in the local degradation
      of extracellular matrix proteins beneath the podosomes and required for the
      invasion of collagen gels by endothelial cells. We propose that TGF-beta plays an
      important role in endothelial cell physiology by inducing the formation of
      podosomal structures endowed with metalloprotease activity that may contribute to
      arterial remodeling.

PMID- 16611999
TI  - Loss of TSLC1 causes male infertility due to a defect at the spermatid stage of
      spermatogenesis.
AB  - Tumor suppressor of lung cancer 1 (TSLC1), also known as SgIGSF, IGSF4, and
      SynCAM, is strongly expressed in spermatogenic cells undergoing the early and
      late phases of spermatogenesis (spermatogonia to zygotene spermatocytes and
      elongating spermatids to spermiation). Using embryonic stem cell technology to
      generate a null mutation of Tslc1 in mice, we found that Tslc1 null male mice
      were infertile. Tslc1 null adult testes showed that spermatogenesis had arrested
      at the spermatid stage, with degenerating and apoptotic spermatids sloughing off
      into the lumen. In adult mice, Tslc1 null round spermatids showed evidence of
      normal differentiation (an acrosomal cap and F-actin polarization
      indistinguishable from that of wild-type spermatids); however, the surviving
      spermatozoa were immature, malformed, found at very low levels in the epididymis,
      and rarely motile. Analysis of the first wave of spermatogenesis in Tslc1 null
      mice showed a delay in maturation by day 22 and degeneration of round spermatids
      by day 28. Expression profiling of the testes revealed that Tslc1 null mice
      showed increases in the expression levels of genes involved in apoptosis,
      adhesion, and the cytoskeleton. Taken together, these data show that Tslc1 is
      essential for normal spermatogenesis in mice.

PMID- 16612000
TI  - Disruption of spermatogenic cell adhesion and male infertility in mice lacking
      TSLC1/IGSF4, an immunoglobulin superfamily cell adhesion molecule.
AB  - TSLC1/IGSF4, an immunoglobulin superfamily molecule, is predominantly expressed
      in the brain, lungs, and testes and plays important roles in epithelial cell
      adhesion, cancer invasion, and synapse formation. We generated Tslc1/Igsf4
      deficient mice by disrupting exon 1 of the gene and found that Tslc1(-/-) mice
      were born with the expected Mendelian ratio but that Tslc1(-/-) male mice were
      infertile. In 11-week-old adult Tslc1(-/-) mice, the weight of a testis was 88%
      that in Tslc1(+/+) mice, and the number of sperm in the semen was approximately
      0.01% that in Tslc1(+/+) mice. Histological analysis revealed that the round
      spermatids and the pachytene spermatocytes failed to attach to the Sertoli cells
      in the seminiferous tubules and sloughed off into the lumen with apoptosis in the
      Tslc1(-/-) mice. On the other hand, the spermatogonia and the interstitial cells,
      including Leydig cells, were essentially unaffected. In the Tslc1(+/+) mice,
      TSLC1/IGSF4 expression was observed in the spermatogenic cells from the
      intermediate spermatogonia to the early pachytene spermatocytes and from
      spermatids at step 7 or later. These findings suggest that TSLC1/IGSF4 expression
      is indispensable for the adhesion of spermatocytes and spermatids to Sertoli
      cells and for their normal differentiation into mature spermatozoa.

PMID- 16612001
TI  - Molecular mechanisms of Ca(2+) signaling in neurons induced by the S100A4
      protein.
AB  - The S100A4 protein belongs to the S100 family of vertebrate-specific proteins
      possessing both intra- and extracellular functions. In the nervous system, high
      levels of S100A4 expression are observed at sites of neurogenesis and lesions,
      suggesting a role of the protein in neuronal plasticity. Extracellular oligomeric
      S100A4 is a potent promoter of neurite outgrowth and survival from cultured
      primary neurons; however, the molecular mechanism of this effect has not been
      established. Here we demonstrate that oligomeric S100A4 increases the
      intracellular calcium concentration in primary neurons. We present evidence that
      both S100A4-induced Ca(2+) signaling and neurite extension require activation of
      a cascade including a heterotrimeric G protein(s), phosphoinositide-specific
      phospholipase C, and diacylglycerol-lipase, resulting in Ca(2+) entry via
      nonselective cation channels and via T- and L-type voltage-gated Ca(2+) channels.
      We demonstrate that S100A4-induced neurite outgrowth is not mediated by the
      receptor for advanced glycation end products, a known target for other
      extracellular S100 proteins. However, S100A4-induced signaling depends on
      interactions with heparan sulfate proteoglycans at the cell surface. Thus,
      glycosaminoglycans may act as coreceptors of S100 proteins in neurons. This may
      provide a mechanism by which S100 proteins could locally regulate neuronal
      plasticity in connection with brain lesions and neurological disorders.

PMID- 16612002
TI  - Normal T-cell development and immune functions in TRIM-deficient mice.
AB  - The transmembrane adaptor molecule TRIM is strongly expressed within thymus and
      in peripheral CD4(+) T cells. Previous studies suggested that TRIM is an integral
      component of the T-cell receptor (TCR)/CD3 complex and might be involved in
      regulating TCR cycling. To elucidate the in vivo function of TRIM, we generated
      TRIM-deficient mice by homologous recombination. TRIM(-/-) mice develop normally
      and are healthy and fertile. However, the animals show a mild reduction in body
      weight that appears to be due to a decrease in the size and/or cellularity of
      many organs. The morphology and anatomy of nonlymphoid as well as primary and
      secondary lymphoid organs is normal. The frequency of thymocyte and peripheral T
      cell subsets does not differ from control littermates. In addition, a detailed
      analysis of lymphocyte development revealed that TRIM is not required for either
      positive or negative selection. Although TRIM(-/-) CD4(+) T cells showed an
      augmented phosphorylation of the serine/threonine kinase Akt, the in vitro
      characterization of peripheral T cells indicated that proliferation, survival,
      activation-induced cell death, migration, adhesion, TCR internalization and
      recycling, TCR-mediated calcium fluxes, tyrosine phosphorylation, and mitogen
      activated protein family kinase activation are not affected in the absence of
      TRIM. Similarly, the in vivo immune response to T-dependent and T-independent
      antigens as well as the clinical course of experimental autoimmune
      encephalomyelitis, a complex Th1-mediated autoimmune model, is comparable to that
      of wild-type animals. Collectively, these results demonstrate that TRIM is
      dispensable for T-cell development and peripheral immune functions. The lack of
      an evident phenotype could indicate that TRIM shares redundant functions with
      other transmembrane adaptors involved in regulating the immune response.

PMID- 16612003
TI  - Recruitment of the type B histone acetyltransferase Hat1p to chromatin is linked
      to DNA double-strand breaks.
AB  - Type B histone acetyltransferases are thought to catalyze the acetylation of the
      NH(2)-terminal tails of newly synthesized histones. Although Hat1p has been
      implicated in cellular processes, such as telomeric silencing and DNA damage
      repair, the underlying molecular mechanisms by which it functions remain elusive.
      In an effort to understand how Hat1p is involved in the process of DNA double
      strand break (DSB) repair, we examined whether Hat1p is directly recruited to
      sites of DNA damage. Following induction of the endonuclease HO, which generates
      a single DNA DSB at the MAT locus, we found that Hat1p becomes associated with
      chromatin near the site of DNA damage. The nuclear Hat1p-associated histone
      chaperone Hif1p is also recruited to an HO-induced DSB with a similar
      distribution. In addition, while the acetylation of all four histone H4 NH(2)
      terminal tail domain lysine residues is increased following DSB formation, only
      the acetylation of H4 lysine 12, the primary target of Hat1p activity, is
      dependent on the presence of Hat1p. Kinetic analysis of Hat1p localization
      indicates that it is recruited after the phosphorylation of histone H2A S129 and
      concomitant with the recombinational-repair factor Rad52p. Surprisingly, Hat1p is
      still recruited to chromatin in strains that cannot repair an HO-induced double
      strand break. These results indicate that Hat1p plays a direct role in DNA damage
      repair and is responsible for specific changes in histone modification that occur
      during the course of recombinational DNA repair.

PMID- 16612004
TI  - The retinoblastoma protein regulates pericentric heterochromatin.
AB  - The retinoblastoma protein (pRb) has been proposed to regulate cell cycle
      progression in part through its ability to interact with enzymes that modify
      histone tails and create a repressed chromatin structure. We created a mutation
      in the murine Rb1 gene that disrupted pRb's ability to interact with these
      enzymes to determine if it affected cell cycle control. Here, we show that loss
      of this interaction slows progression through mitosis and causes aneuploidy. Our
      experiments reveal that while the LXCXE binding site mutation does not disrupt
      pRb's interaction with the Suv4-20h histone methyltransferases, it dramatically
      reduces H4-K20 trimethylation in pericentric heterochromatin. Disruption of
      heterochromatin structure in this chromosomal region leads to centromere fusions,
      chromosome missegregation, and genomic instability. These results demonstrate the
      surprising finding that pRb uses the LXCXE binding cleft to control chromatin
      structure for the regulation of events beyond the G(1)-to-S-phase transition.

PMID- 16612005
TI  - An HMG protein, Hmo1, associates with promoters of many ribosomal protein genes
      and throughout the rRNA gene locus in Saccharomyces cerevisiae.
AB  - HMG proteins are architectural proteins that bind to DNA with low sequence
      specificity, but little is known about their genomic location and biological
      functions. Saccharomyces cerevisiae encodes 10 HMG proteins, including Hmo1,
      which is important for maximal transcription of rRNA. Here we use chromatin
      immunoprecipitation coupled with microarray analysis to determine the genome-wide
      association of Hmo1. Unexpectedly, Hmo1 binds strongly to the promoters of most
      ribosomal protein (RP) genes and to a number of other specific genomic locations.
      Hmo1 binding to RP promoters requires Rap1 and (to a lesser extent) Fhl1,
      proteins that also associate with RP promoters. Hmo1, like Fhl1 and Ifh1,
      typically associates with an IFHL motif in RP promoters, but deletion of the IFHL
      motif has a very modest effect on Hmo1 binding. Surprisingly, loss of Hmo1
      abolishes binding of Fhl1 and Ifh1 to RP promoters but does not significantly
      affect the level of transcriptional activity. These results suggest that Hmo1 is
      required for the assembly of transcription factor complexes containing Fhl1 and
      Ifh1 at RP promoters and that proteins other than Fhl1 and Ifh1 also play an
      important role in RP transcription. Lastly, like mammalian UBF, Hmo1 associates
      at many locations throughout the rRNA gene locus, and it is important for
      processing of rRNA in addition to its role in rRNA transcription. We speculate
      that Hmo1 has a role in coordinating the transcription of rRNA and RP genes.

PMID- 16612006
TI  - Genetic variation of farrowing kinetics traits and their relationships with
      litter size and perinatal mortality in French Large White sows.
AB  - Genetic parameters of litter traits and their relationships with farrowing
      kinetics traits were estimated in a Large White population to examine the impact
      of selection for litter size on perinatal mortality and one of its main
      determinants, farrowing kinetics. Data were collected on 2,947 farrowings from
      1,267 sows between 1996 and 2004. Litter traits included the number born in total
      (NBT), number born alive (NBA), and the number (NSB) and proportion (PSB) of
      stillborn piglets. Four farrowing kinetics traits were considered: farrowing
      duration (FD), birth interval (BI = FD/NBT), heterogeneity of birth intervals
      (SDNB = SD of the number of piglets born each one-half hour), and birth
      assistance (BA) during the farrowing process. Genetic parameters were estimated
      using restricted maximum likelihood methodology. All traits were analyzed using a
      mixed linear animal model including year x month and parity as fixed effects; the
      additive genetic value of each animal and the sow permanent environment were
      treated as random effects. To normalize their distribution, kinetics traits were
      Box-Cox-transformed. Low heritability estimates were obtained for litter size and
      mortality traits, which was in agreement with literature results (i.e., 0.10 +/-
      0.02, 0.08 +/- 0.02, 0.19 +/- 0.02, and 0.14 +/- 0.02 for NBT, NBA, NSB, and PSB,
      respectively). Heritability values were also low for kinetics traits: 0.10 +/-
      0.02, 0.08 +/- 0.02, 0.01 +/- 0.01, and 0.05 +/- 0.03 for FD, BI, SDNB, and BA,
      respectively. The genetic correlation between NBT and NBA was strongly positive
      (ra = 0.90). On both phenotypic and genetic scales, NBT was positively associated
      with stillbirth (ra = 0.45 +/- 0.11, rp = 0.38 for NSB; ra = 0.46 +/- 0.13, rp =
      0.17 for PSB). Conversely, NBA had low correlations with SB and PSB. Number born
      in total was moderately correlated to FD (ra = 0.34 +/- 0.15) and BI (ra = -0.37
      +/- 0.15). A stronger relationship was found between NBA and BI (ra = -0.49 +/-
      0.13), whereas the relationship with FD was lower (ra = 0.16 +/- 0.17). Moreover,
      FD was strongly correlated with stillbirth (ra = 0.42 +/- 0.12 with NSB), whereas
      BI was nearly independent of stillbirth. Contrary to selection on NBT, selection
      on NBA appears to be a good way to limit the negative side effects on stillbirth.
      Moreover, selection on NBA would lead to a small increase in FD and a faster and
      more regular birth process than would be obtained by selecting on NBT.

PMID- 16612007
TI  - The expression of genes related to adipocyte differentiation in pigs.
AB  - The purpose of this study was to detect differential expression of genes related
      to adipocyte differentiation in pigs by suppression subtractive hybridization.
      Adipocytes and stromal vascular cells (a fraction containing preadipocytes) from
      pig adipose tissue were isolated for mRNA extraction. The cDNA from preadipocytes
      was subtracted from the cDNA from adipocytes. The subtracted gene fragments were
      cloned into pGEM-T Easy TA cloning vector. We selected 384 clones for gene
      sequence determination and for further analysis. These genes were subjected to a
      differential screening procedure to confirm the differential expression of genes
      between the 2 cell types. We found that at least 36 genes were highly expressed
      in the adipocytes compared with preadipocytes. Among these, 6 genes including 2
      novel genes with the greatest differences were selected and confirmed by Northern
      analysis. We found that angiotensin I-converting enzyme (ACE), ataxia
      telangiectasia mutated protein (ATM), calpain 1, and stearoyl coenzyme A
      desaturase 1 (SCD1) were highly expressed in adipocytes compared with
      preadipocytes (P < 0.05). The relative mRNA abundance of ACE, ATM, calpain 1,
      SCD1, and 2 novel genes discovered in the current study was increased at the
      later stages of adipocyte differentiation (P < 0.05). The results confirmed that
      the genes involved in lipid metabolism and adipocyte differentiation were highly
      expressed in porcine adipocytes. However, further investigation is needed to
      demonstrate specific functions of the novel genes discovered in the current
      study.

PMID- 16612008
TI  - Growth- and breed-related changes of marbling characteristics in cattle.
AB  - The objective of this study was to investigate the growth- and breed-related
      changes of marbling characteristics in cattle. Four cattle breeds with different
      growth impetus and muscularity were reared and slaughtered under experimental
      conditions. German Angus, as a typical beef cattle; Galloway, as a smaller,
      environmentally resistant beef cattle; Holstein-Friesian, as a dairy-type cattle;
      and double-muscled Belgian Blue, as an extreme type for muscle growth, were used.
      These 4 breeds were expected to have differences in muscle development and i.m.
      fat deposition. Between 5 and 15 bulls of each breed were slaughtered at 2, 4, 6,
      12, or 24 mo of age. Marbling characteristics were determined and classified in
      LM and semitendinosus muscle by computerized image analysis. Among breeds,
      differences appeared in the quantity, structure, and distribution of the marbling
      flecks in both muscles. The deposition of fat in the double-muscled Belgian Blue
      bulls remained substantially inferior to that of the other breeds, up to the age
      of 24 mo. Marbling in German Angus bulls particularly showed larger (P < 0.05)
      marbling fleck areas. Galloway cattle had the greatest (P < 0.05) number and the
      most regular (P < 0.05) distribution of the marbling flecks in young animals.
      Furthermore, for marbling characteristics in Holstein-Friesian animals, a great
      number and slightly finer structure were observed compared with the other breeds
      investigated. Postnatal growth-related changes of marbling in LM were
      characterized by as much as a 40-fold increase in the number of marbling flecks
      from 2 to 24 mo of age but also by up to a 4-fold enlargement in the area of the
      marbling flecks. The structure of marbling flecks was determined by 2 development
      trends. On the one hand, the marbling flecks became larger (P < 0.05), and the
      structure became coarser, which was reflected by an increasing (P < 0.01)
      proportion of long marbling flecks as well as an increasing (P < 0.01) maximum
      skeleton line length. On the other hand, continually new small, round marbling
      flecks appeared. This caused a decrease (P < 0.01) in the proportion of the 3
      largest marbling fleck areas. The distribution of the marbling flecks became more
      regular (P < 0.05) with increasing proportion and number of marbling flecks. The
      results suggest that hyperplasia of adipocytes plays an important role in
      marbling during growth of muscle in cattle.

PMID- 16612009
TI  - A comparison of thiazolidinedione-induced adipogenesis and myogenesis in stromal
      vascular cells from subcutaneous adipose tissue or semitendinosus muscle of
      postnatal pigs.
AB  - This study compared the adipogenic potential of porcine stromal-vascular (S-V)
      cells from semitendinosus muscles and s.c. adipose tissue using
      thiazolidinediones. Stromal-vascular cells were obtained from s.c. adipose tissue
      and both semitendinosus muscles from 5- to 7-d-old pigs after collagenase
      digestion. Preadipocyte recruitment was measured using immunohistological
      evaluation for AD-3, a preadipocyte antibody. Ciglitazone increased the number of
      preadipocytes in adipose tissue but not semitendinosus muscle S-V cell cultures,
      whereas 10 microM troglitazone increased preadipocyte abundance in both adipose
      and muscle S-V cultures by approximately 3-fold (P < 0.05). Increasing
      troglitazone doses did not further increase preadipocyte number. Increases in
      preadipocytes were paralleled by increases in CCAAT/enhancer-binding protein
      alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma
      (PPARgamma) positive cells in adipose tissue S-V cultures, whereas PPARgamma
      reactive but not C/EBPalpha-reactive cells were increased in muscle S-V cultures
      treated with 10 microM troglitazone. Additionally, troglitazone treatment did not
      increase lipid content in s.c. adipose tissue or muscle S-V cell cultures. Cells
      plated on laminin-precoated culture dishes were used to determine whether
      troglitazone influenced adipogenesis or myogenesis in cocultures from muscle S-V
      cells. There was no effect on the number of myotubes or the average number of
      nuclei per myotube, suggesting myogenesis was not impaired by troglitazone
      treatment. These results suggest that regulation of intramuscular adipogenesis
      differs from that of subcutaneous adipogenesis.

PMID- 16612010
TI  - Number of intramuscular adipocytes and fatty acid binding protein-4 content are
      significant indicators of intramuscular fat level in crossbred Large White x
      Duroc pigs.
AB  - Intramuscular fat content is generally associated with improved sensory quality
      and better acceptability of fresh pork. However, conclusive evidence is still
      lacking for the biological mechanisms underlying i.m. fat content variability in
      pigs. The current study aimed to determine whether variations in i.m. fat content
      of longissimus muscle are related to i.m. adipocyte cellularity, lipid
      metabolism, or contractile properties of the whole muscle. To this end, crossbred
      (Large White x Duroc) pigs exhibiting either a high (2.82 +/- 0.38%, HF) or a low
      (1.15 +/- 0.14%, LF) lipid content in LM biopsies at 70 kg of BW were further
      studied at 107 +/- 7 kg of BW. Animals grew at the same rate, but HF pigs at
      slaughter presented fatter carcasses than LF pigs (P = 0.04). The differences in
      i.m. fat content between the 2 groups were mostly explained by variation in i.m.
      adipocyte number (+127% in HF compared with LF groups, P = 0.005). Less
      difference (+13% in HF compared with LF groups, P = 0.057) was noted in adipocyte
      diameter, and no significant variation was detected in whole-muscle lipogenic
      enzyme activities (acetyl-CoA carboxylase, P = 0.9; malic enzyme, P = 0.35;
      glucose-6-phosphate dehydrogenase, P = 0.75), mRNA levels of sterol-regulatory
      element binding protein-1 (P = 0.6), or diacylglycerol acyltransferase 1 (P =
      0.6). Adipocyte fatty acid binding protein (FABP)-4 protein content in whole LM
      was 2-fold greater in HF pigs than in LF pigs (P = 0.05), and positive
      correlation coefficients were found between the FABP-4 protein level and
      adipocyte number (R2 = 0.47, P = 0.02) and lipid content (R2 = 0.58, P = 0.004).
      Conversely, there was no difference between groups relative to FABP-3 mRNA (P =
      0.46) or protein (P = 0.56) levels, oxidative enzymatic activities (citrate
      synthase, P = 0.9; beta-hydroxyacyl-CoA dehydrogenase, P = 0.7), mitochondrial (P
      = 0.5) and peroxisomal (P = 0.12) oxidation rates of oleate, mRNA levels of genes
      involved in fatty acid oxidation (carnitine-palmitoyl-transferase 1, P = 0.98;
      peroxisome proliferator-activated receptor delta, P = 0.73) or energy expenditure
      (uncoupling protein 2, P = 0.92; uncoupling protein 3, P = 0.84), or myosin heavy
      chain mRNA proportions (P > 0.49). The current study suggests that FABP-4 protein
      content may be a valuable marker of lipid accretion in LM and that i.m. fat
      content and myofiber type composition can be manipulated independently.

PMID- 16612011
TI  - Maintenance of body temperature in the neonatal lamb: effects of breed, birth
      weight, and litter size.
AB  - To survive, the newborn lamb must be able to maintain body temperature and to
      stand and move to the udder to suck colostrum to fuel heat production. The
      objective of this study was to investigate whether neonatal lambs showing slow
      behavioral progress to standing and sucking also have an impaired ability to
      maintain body temperature. The time taken to stand and suck after birth, rectal
      temperatures, and blood samples were collected from 115 newborn single, twin, and
      triplet lambs of 2 breeds, Scottish Blackface and Suffolk, which are known to
      show variations in their neonatal behavioral progress. Blood samples were assayed
      for thyroid hormones, known to be involved in heat production, and cortisol,
      which plays a role in tissue maturation before birth. In addition, colostrum
      samples were collected from the 56 ewes that gave birth to the lambs, and assayed
      for protein, fat, and vitamin contents. Heavy lambs (more than 1 SD above the
      breed mean), Blackface lambs, and singleton or twin lambs were quicker to stand
      and suck from their mothers than lightweight (more than 1 SD below the breed
      mean), Suffolk, or triplet lambs. Low birth weight lambs also had lower rectal
      temperatures than heavier lambs (P < 0.01), as did Suffolk compared with
      Blackface lambs (P < 0.001). Lambs that were slow to suck after birth had lower
      rectal temperatures than quick lambs, and this difference persisted for at least
      3 d after birth. Within breed, heavy lambs had greater plasma triiodothyronine
      and thyroxine immediately after birth than light lambs. Blackface lambs had
      greater plasma triiodothyronine and thyroxine than Suffolk lambs but tended to
      have less cortisol. Colostrum produced by Blackface ewes had a greater fat
      content than that of Suffolk ewes (P < 0.001). Thus, lambs that are behaviorally
      slow at birth are also less able to maintain their body temperature after birth.
      Although part of their lower body temperature might be attributable to behavioral
      influences on thermoregulation, the data also suggest that physiological
      differences exist between these animals. These differences may be related to
      different degrees of maturity at birth.

PMID- 16612012
TI  - Diet-induced alterations in progesterone clearance appear to be mediated by
      insulin signaling in hepatocytes.
AB  - Factors that affect progesterone clearance from plasma and by hepatocytes in
      culture were examined in a series of experiments. In Exp. 1, the objective was to
      determine whether an increase in hepatic portal blood acetate or propionate could
      alter progesterone metabolism by the liver. For ewe lambs gavaged orally with
      sodium propionate compared with those gavaged orally with sodium acetate, serum
      progesterone concentrations began to diverge as early as 0.5 h after
      administration and were greater (P < 0.05) at 3 and 4 h after administration. The
      objective of Exp. 2 was to determine the effect of a single oral gavage of either
      sodium acetate or sodium propionate on peripheral insulin and glucagon
      concentrations. Ewes gavaged orally with sodium propionate had greater (P < 0.05)
      insulin concentrations at 0.5 and 1 h after gavage than ewes gavaged with sodium
      acetate. Furthermore, glucagon concentrations were greater (P < 0.05) at 0.5, 1,
      and 2 h for ewe lambs gavaged orally with sodium propionate compared with those
      receiving sodium acetate. The third experiment investigated the rate of in vitro
      progesterone clearance by cultured hepatocytes in response to treatment with
      different concentrations of insulin and glucagon. Progesterone clearance was
      reduced (P < 0.05) with the addition of 0.1 nM insulin compared with the control.
      Furthermore, there was a greater reduction (P < 0.05) in progesterone clearance
      in response to 1.0 and 10 nM insulin compared with the control and 0.1 nM
      insulin. No change was observed in progesterone clearance in hepatocytes treated
      with either physiological (0.01 and 0.1 nM) or supraphysiological (1.0 nM)
      glucagon. Supraphysiological concentrations of glucagon (1.0 nM) negated the
      effects of either 0.1 or 1.0 nM insulin on progesterone clearance by hepatocytes.
      However, with physiological concentrations of glucagon (0.1 nM) and 1.0 nM
      insulin, glucagon was not able to negate the reduction in progesterone clearance
      caused by insulin. These data are consistent with a paradigm in which elevated
      hepatic portal vein propionate increases plasma insulin in ruminants, which
      decreases progesterone clearance, thereby increasing serum progesterone
      concentrations.

PMID- 16612013
TI  - Use of the in vitro cumulative gas production technique for pigs: an examination
      of alterations in fermentation products and substrate losses at various time
      points.
AB  - An experiment was conducted to examine changes in VFA and ammonia concentrations
      at different time points using 4 fermentable carbohydrate-rich feed ingredients
      as substrates and feces of unweaned piglets as inoculum. Fecal inoculum was
      collected, pooled, and mixed from 9 specially raised (no creep feed or
      antibiotics) crossbred piglets at 3 wk of age. Inulin, lactulose, molasses-free
      sugar beet pulp, and wheat starch were used as substrates and were fermented in
      vitro for 72 h (3 replicates per substrate). Cumulative gas production was
      measured as an indicator of the kinetics of fermentation. In addition, 3 bottles
      of substrate per time point with similar contents (amounts of substrate,
      inoculum, and media) were incubated but were allowed to release their gas
      throughout incubation. For these latter bottles, fermentation fluid was sampled
      at incubation time points including every hour between 1 and 24 h and at 48 h,
      and fermentation end products (VFA, lactate, and ammonia) and OM disappearance
      were measured. Dry matter and ash were analyzed from the postfermentative
      samples. The pH of the contents from these bottles was also recorded. The
      correlation in time between fermentation end products and cumulative gas produced
      was determined. The results showed that the prolongation of fermentation to 72 h,
      especially in the case of fast-fermenting inulin and lactulose, may lead to a
      different end product profile (P < 0.001) compared with the profile observed at
      the time at which most of the substrate has disappeared. Therefore, we concluded
      that the fermentation product profile at the end of in vitro fermentation at a
      specific time point cannot be used to compare fermentability of carbohydrate
      sources with different fermentation kinetics in terms of gas production.

PMID- 16612014
TI  - Estimating equivalency values of microbial phytase for amino acids in growing and
      finishing pigs fitted with steered ileo-cecal valve cannulas.
AB  - Ten crossbred barrows (48.3 +/- 2.3 kg of initial BW) fitted with steered ileo
      cecal valve cannulas were used to investigate the effects of supplemental
      microbial phytase on the apparent ileal digestibilities (AID) of AA, Ca, P, N,
      and DM, and the apparent total tract digestibilities of Ca, P, N, and DM. All
      diets were corn-soybean meal-based, and contained 0.44% Ca and 0.40% total P.
      Diets 1, 2, and 3 contained 12.0, 11.1, and 10.2% CP, respectively. Diets 4 and 5
      had the same ingredient composition as diet 3, plus 250 and 500 U/kg phytase
      (Natuphos), respectively. Pigs were randomly allotted to 1 of 5 dietary
      treatments in a paired 5 x 5 Latin square with an extra period to test for
      carryover effects. Each 14-d period consisted of a 7-d adjustment followed by a 3
      d total collection, a 12-h ileal digesta collection, a 3-d readjustment, and a
      second 12-h ileal digesta collection. Pigs were housed individually in metabolism
      pens (1.2 x 1.2 m). Water was supplied ad libitum, and feed was supplied at a
      level of 9% of the metabolic BW (BW(0.75)) per day in 2 equal daily feedings. As
      the dietary CP concentration increased, the AID of CP and all AA measured
      increased linearly (P < 0.05) with the exception of proline. In addition, the
      apparent total tract digestibilities (grams per day) and retention of N (grams
      per day) increased linearly (P < 0.01) with increasing CP levels. Supplementing
      diets with phytase increased the AID of Ca (P < 0.01), P (P < 0.001), CP (P =
      0.07), and the AA (P < 0.10) Gly, Ala, Val, Ile, Thr, TSAA, Asp, Glu, Phe, Lys,
      and Arg. Protein and phytase response equations were generated for those AA
      affected (P < 0.10) by both CP level and phytase supplementation. Based on these
      equations, 500 U/kg of phytase can replace 0.52 percentage units of the dietary
      CP, which includes a 0.03 percentage unit improvement in Lys AID. The results of
      this study show that supplementing pig diets with microbial phytase improves CP
      and AA digestibilities in addition to Ca and P digestibilities.

PMID- 16612015
TI  - Amino acid digestibility in dry extruded-expelled soybean meal fed to pigs and
      poultry.
AB  - The digestibility of AA in dry extruded-expelled soybean meal (DESBM) and
      regular, solvent-extracted soybean meal (SBM) were determined in pigs and
      poultry. In the pig assay, 4 Cotswold barrows (average initial BW of 80.4 kg)
      fitted with a T-cannula at the distal ileum were allotted to 4 semipurified diets
      in a 4 x 4 Latin square design. Diet 1, a low protein diet (5% casein), was used
      to quantify endogenous CP and AA losses. Diets 2, 3, and 4 were formulated to
      contain 35% regular, solvent-extracted SBM; batch 1 of DESBM (DESBM-1); and batch
      2 of DESBM (DESBM-2), respectively, as the sole source of protein. The DESBM
      samples were obtained from 2 different batches but were subjected to the same
      processing conditions. Chromic oxide (0.3%) was included as a digestibility
      marker in all diets. Compared with DESBM-1 and DESBM-2, apparent ileal
      digestibility of DM in SBM was greater (P < 0.05). Apparent and true ileal
      digestibilities of AA in SBM were greater (P < 0.05) compared with DESBM-2. In
      the poultry assay, 4 dietary treatments were each assigned to adult cecectomized
      roosters in a completely randomized design. Treatment 1 was a nonnitrogenous diet
      (NND; 90% sucrose and 10% vegetable oil) used to estimate endogenous N and AA
      losses. Treatments 2, 3, and 4 contained SBM, DESBM-1, and DESBM-2 as the only
      source of protein. Each of these diets was fed in 25-g quantities formulated to
      provide 5 g of CP from the respective soybean meal source. The SBM had greater (P
      < or = 0.05) true digestibility for isoleucine, leucine, cysteine, proline,
      serine, and tyrosine compared with DESBM-1. The results indicate that, relative
      to regular, solvent-extracted soybean meal, AA digestibilities of different
      batches of dry extruded-expelled soybean meal varied in pigs and poultry.

PMID- 16612016
TI  - Impact of supplement withdrawal and wheat middling inclusion on bone metabolism,
      bone strength, and the incidence of bone fractures occurring at slaughter in
      pigs.
AB  - The objective of this study was to determine if supplement withdrawal (omission
      of dietary vitamin and trace mineral premixes and 2/3 of inorganic P) 28-d
      preslaughter and the feeding of wheat middlings (dietary concentrations of 5, 15,
      or 30% from weaning to 16 kg, 16 to 28 kg, and 28 kg to slaughter, respectively)
      affect bone metabolism, bone strength, bone density, and the incidence of bone
      fractures at slaughter in pigs. Crossbred barrows (n = 64) were assigned to a 2 x
      2 factorial arrangement of treatments (with or without supplement withdrawal, and
      with or without wheat middlings). Serum was collected on d 0, 14, and 27 of the
      preslaughter withdrawal period to determine changes in the concentrations of
      osteocalcin, an indicator of bone formation, and pyridinoline, an indicator of
      bone resorption. The serum osteocalcin and pyridinoline concentrations on d 14
      and 27 were analyzed as change from the d-0 concentration. At slaughter,
      radiographs of the lumbar vertebrae and of the right and left femurs were taken
      to determine the incidence of bone fractures. Third metacarpal bones were
      analyzed for bone mineral density, peak load, ultimate shear stress, and percent
      ash. Supplement withdrawal increased (P < 0.05) serum osteocalcin and
      pyridinoline concentrations, indicating an increase in osteoblast activity and
      bone resorption. Supplement withdrawal decreased (P < 0.01) bone mineral density,
      peak load, ultimate shear stress, and percent ash of the metacarpal bones.
      Dietary wheat middling inclusion did not alter bone quality. Neither supplement
      withdrawal nor wheat middling inclusion affected the incidence of bone fractures
      at slaughter. The results of this study indicate that removing inorganic P,
      vitamin premix, and trace mineral premix for 28 d preslaughter increases bone
      turnover and decreases bone quality.

PMID- 16612017
TI  - A genetically engineered Escherichia coli phytase improves nutrient utilization,
      growth performance, and bone strength of young swine fed diets deficient in
      available phosphorus.
AB  - A 28-d experiment was conducted using 126 crossbred barrows to evaluate the
      addition of a genetically engineered Escherichia coli phytase to diets that were
      0.15% deficient in available P. Growth performance, bone strength, ash weight,
      and the apparent absorption of P, Ca, Mg, N, energy, DM, Zn, Fe, and Cu were the
      response criteria. The pigs (2 pigs/pen) averaged 7.61 kg of BW and 30 d of age
      initially. The low-P basal diet was supplemented with 0, 100, 500, 2,500, or
      12,500 units (U) of E. coli phytase/kg of diet, or 500 U of Peniophora lycii
      phytase/kg of diet. The positive control (PC) diet was adequate in available P.
      Pigs were fed the diets in meal form. Fecal samples were collected from each pig
      from d 22 to 27 of the experiment. There were linear and quadratic increases (P <
      0.001) in 28-d growth performance (ADFI, ADG, and G:F), bone breaking strength
      and ash weight, and the apparent absorption (g/d and %) of P, Ca, and Mg (P < or
      = 0.01 for quadratic) with increasing concentrations of E. coli phytase. Pigs fed
      the low-P diets containing 2,500 or 12,500 U/kg of E. coli phytase had greater (P
      < or = 0.01 or P < 0.001, respectively) values for growth performance, bone
      breaking strength and ash weight, and the apparent absorption (g/d and %) of P,
      Ca, and Mg than pigs fed the PC diet. The addition of E. coli phytase did not
      increase the apparent percentage absorption of N, GE, DM, Zn, Fe, or Cu. There
      were no differences in the efficacy of the E. coli or P. lycii phytase enzymes at
      500 U/kg of low-P diet for any criterion measured. In conclusion, there were
      linear increases in growth performance, bone breaking strength and ash weight,
      and the apparent absorption of P, Ca, and Mg with increasing addition of E. coli
      phytase up to 12,500 U/kg of diet. Also, all of these criteria were greater for
      pigs fed the low-P diets containing 2,500 or 12,500 U of E. coli phytase/kg than
      for pigs fed the PC diet. The addition of 500, 2,500, or 12,500 U of E. coli
      phytase/kg of low-P diet reduced P excretion (g/d) in manure by 35, 42, and 61%,
      respectively, compared with pigs fed the PC diet.

PMID- 16612018
TI  - The effects of dietary energy concentration and weaning site on weanling pig
      performance.
AB  - This study was conducted to evaluate the effects of dietary energy density and
      weaning environment on pig performance. Treatment diets were formulated to vary
      in DE concentration by changing the relative proportions of low (barley) and high
      (wheat, oat groats, and canola oil) energy ingredients. In Exp. 1, 84 pigs in
      each of 3 replications, providing a total of 252 pigs, were weaned at 17 x 2 d of
      age and randomly assigned to either an on-site or an off-site nursery and to 1 of
      3 dietary DE concentrations (3.35, 3.50, or 3.65 Mcal/kg). Each site consisted of
      a nursery containing 6 pens; 3 pens housed 7 barrows and 3 housed 7 gilts. All
      pigs received nontreatment diets in phase I (17 to 19 d of age) and phase II (20
      to 25 d of age), respectively. Dietary treatments were fed from 25 to 56 d of
      age. Off-site pigs were heavier at 56 d of age (23.4 vs. 21.3 kg; P < 0.05) and
      had greater ADFI (0.77 vs. 0.69 kg/d; P < 0.01) than on-site pigs. There was a
      linear decrease in ADG (P < 0.01) and ADFI (P < 0.001) with increasing DE
      concentration. Efficiency of gain improved (P < 0.01) with increasing DE
      concentration. There was no interaction between weaning site and diet DE
      concentration, indicating that on-site and off-site pigs responded similarly to
      changes in diet DE concentration. In Exp. 2, nutrient digestibility of the
      treatment diets used in Exp. 1 was determined using 36 pigs with either ad
      libitum or feed intake restricted to 5.5% of BW. Energy and N digestibility
      increased (P < 0.001) with increasing DE concentration. Nitrogen retention and
      daily DE intake increased with DE concentration in pigs fed the restricted amount
      of feed (P < 0.05). These results indicate that weaning off-site improves pig
      weight gain. The weanling pig was able to compensate for reduced dietary DE
      concentration through increased feed intake. Growth limitation in the weanling
      pig may not be overcome simply by increasing dietary DE concentration.

PMID- 16612019
TI  - Effect of graded doses and a high dose of microbial phytase on the digestibility
      of various minerals in weaner pigs.
AB  - An experiment with 224 weaner pigs (initial BW of 7.8 kg) was conducted to
      determine the effect of dose of dietary phytase supplementation on apparent fecal
      digestibility of minerals (P, Ca, Mg, Na, K, and Cu) and on performance. Four
      blocks, each with 8 pens of 7 pigs, were formed. Eight dietary treatments were
      applied to each block in the 43-d experiment: supplementation of 0 (basal diet),
      100, 250, 500, 750, 1,500, or 15,000 phytase units (FTU) or of 1.5 g of
      digestible P (dP; monocalcium phosphate; positive control) per kilogram of feed.
      The basal diet, with corn, barley, soybean meal, and sunflower seed meal as the
      main components, contained 1.2 g of dP per kilogram of feed. Fresh fecal grab
      samples were collected in wk 4 and 5 of the experiment. Average daily feed
      intake, ADG, G:F, and digestibility of all of the minerals increased (P < 0.001)
      with increasing phytase dose. Digestibility of P increased from 34% in the basal
      diet to a maximum of 84% in the diet supplemented with 15,000 FTU, generating
      1.76 g of dP per kilogram of feed. At this level, 85% of the phytate phosphorus
      was digested, compared with 15% in the basal diet. Compared with the basal diet,
      digestibility of the monovalent minerals increased maximally at 15,000 FTU, from
      81 to 92% (Na) and from 76 to 86% (K). In conclusion, phytase supplementation up
      to a level of 15,000 FTU/kg of a dP-deficient diet improved performance of weaner
      pigs and digestibility of minerals, including monovalent minerals. Up to 85% of
      the phytate-P was digested. Thus, dietary phytase supplementation beyond present
      day standards (500 FTU/kg) could further improve mineral use and consequently
      reduce mineral output to the environment.

PMID- 16612020
TI  - Use of bovine somatotropin for increased skeletal and lean tissue growth of
      Holstein steers.
AB  - One hundred-sixty Holstein growing-finishing steers (initial BW of 185 kg) were
      blocked by BW to determine the effectiveness of long-term bovine somatotropin
      (bST) administration on lean, skeletal, and carcass measurements. Steers were
      randomly allocated to 4 treatments (10 steers/treatment) within a block (n = 4
      blocks). Treatments were control, no bST (C-C); bST from d 0 to 182 (bST-C); bST
      from d 183 to slaughter (C-bST); and bST from d 0 to slaughter (bST-bST). Steers
      received a s.c. injection of placebo or bST at 14-d intervals. Doses were 320 mg
      of bST/injection from d 0 to 112 and 640 mg of bST/injection from d 113 to
      slaughter. The last treatment was administered 31 d before slaughter. Steers
      received a 14% CP (DM basis) diet from d 0 to 182 and 11.5% CP from d 183 to
      slaughter that consisted of dry, whole-shelled corn and a pelleted protein
      mineral supplement. Steers were slaughtered when BW per block averaged 615 kg (d
      325, 353, 367, and 381 for the 4 blocks, respectively). Thirty steers were
      removed from the study because of poor performance with respect to their pen
      mates, illness, lameness, death, incomplete castration, and incorrect treatment.
      Serum IGF-I concentrations increased 151% (P < 0.01) from d 7 through 35 in bST
      treated steers compared with control steers. During the first 182 d, bST-C and
      bST-bST steers were heavier (P < 0.01) and had greater (P < 0.01) ADG, G:F, hip
      height, and hip height gain compared with C-C and C-bST steers. From d 183 to
      slaughter, C-bST steers had reduced (P < 0.05) daily DMI and greater G:F than bST
      C steers. At final slaughter, C-bST and bST-bST steers had greater (P < 0.05) hip
      height than C-C steers. Noncarcass weight was increased and dressing percent
      reduced (P < 0.05) in C-bST and bST-bST steers compared with C-C steers. Quality
      grade was least (P < 0.05) in bST-bST carcasses compared with C-C, whereas bST-C
      and C-bST carcasses were intermediate. At final slaughter, steers receiving bST
      had greater (P < 0.05) carcass protein and water composition and lower (P < 0.05)
      carcass lipid and lipid accretion than C-C steers. Bovine somatotropin was
      effective in reducing carcass fat and increasing edible lean. Administering bST
      to young, lightweight steers increased skeletal growth and noncarcass weight
      without an increase in total carcass weight, but decreased carcass quality.

PMID- 16612021
TI  - Effects of nonstructural carbohydrates and protein sources on intake, apparent
      total tract digestibility, and ruminal metabolism in vivo and in vitro with high
      concentrate beef cattle diets.
AB  - To investigate the effects of synchronizing nonstructural carbohydrate (NSC) and
      protein degradation on intake and rumen microbial fermentation, four ruminally
      fistulated Holstein heifers (BW = 132.3 +/- 1.61 kg) fed high-concentrate diets
      were assigned to a 4 x 4 Latin square design with a 2 x 2 factorial arrangement
      of treatments studied in vivo and in vitro with a dual-flow continuous culture
      system. Two NSC sources (barley and corn) and 2 protein sources [soybean meal
      (SBM) and sunflower meal (SFM)] differing in their rate and extent of ruminal
      degradation were combined resulting in a synchronized rapid fermentation diet
      (barley-SFM), a synchronized slow fermentation diet (corn-SBM), and 2
      unsynchronized diets with a rapidly and a slowly fermenting component (barley
      SBM, and corn-SFM). In vitro, the fermentation profile was studied at a constant
      pH of 6.2, and at a variable pH with 12 h at pH 6.4 and 12 h at pH 5.8.
      Synchronization tended to result in greater true OM digestion (P = 0.072), VFA
      concentration (P = 0.067), and microbial N flow (P = 0.092) in vitro, but had no
      effects on in vivo fermentation pattern or on apparent total tract digestibility.
      The NSC source affected the efficiency of microbial protein synthesis in vitro,
      tending to be greater (P = 0.07) for barley-based diets, and in vivo, the NSC
      source tended to affect intake. Dry matter and OM intake tended to be greater (P
      > or = 0.06) for corn- than barley-based diets. Ammonia N concentration was lower
      in vitro (P = 0.006) and tended to be lower in vivo (P = 0.07) for corn- than
      barley-based diets. In vitro, pH could be reduced from 6.4 to 5.8 for 12 h/d
      without any effect on ruminal fermentation or microbial protein synthesis. In
      summary, ruminal synchronization seemed to have positive effects on in vitro
      fermentation, but in vivo recycling of endogenous N or intake differences could
      compensate for these effects.

PMID- 16612022
TI  - Effects of dietary nonstructural carbohydrates and protein sources on feeding
      behavior of tethered heifers fed high-concentrate diets.
AB  - To describe the feeding behavior of growing heifers fed high-concentrate diets
      with different sources of protein and nonstructural carbohydrates, and to explain
      the ruminal fermentation pattern, 4 ruminally fistulated Holstein heifers (BW =
      132.3 +/- 1.61 kg) were assigned to a 4 x 4 Latin square design with a 2 x 2
      factorial arrangement of treatments. Two non-structural carbohydrate sources
      (barley and corn) and 2 protein sources [soybean meal (SBM) and sunflower meal
      (SFM)] that differ in their rate and extent of ruminal degradation were combined,
      resulting in a synchronized, rapid fermentation diet (barley-SFM), a
      synchronized, slow fermentation diet (corn-SBM), and 2 unsynchronized diets
      consisting of a rapidly and a slowly fermenting component (barley-SBM and corn
      SFM). The corn-SFM diet resulted in a lower frequency of feeding (P < or = 0.05),
      longer meal length (P < or = 0.043), and larger meal size (P < or = 0.037) than
      the other 3 diets. Dietary treatment had no effect (P > or = 0.09) on the daily
      percentages of posture and behaviors. In general, heifers spent 9.97 +/- 0.83% of
      the day eating, 2.11 +/- 0.42% drinking, 25.13 +/- 1.36% ruminating, 16.97 +/-
      1.42% in other activities such as social behavior and self-grooming, and the rest
      of the day (45.82 +/- 2.55%) resting or doing no chewing activities. Eating,
      drinking, and social behaviors were performed while standing (P < or = 0.01),
      whereas resting and ruminating occurred mainly while lying (P = 0.001). Eating
      took place mainly in the first 4 h after feeding (P = 0.001), whereas ruminating
      occurred mainly at night (P = 0.001). When chewing activities (eating and
      ruminating) were expressed per kilogram of DM or NDF from roughage intake, more
      time (P = 0.004) was spent chewing per kilogram of DMI for barley-based diets,
      and per kilogram of NDF from roughage intake for barley- (P = 0.01) and SFM- (P =
      0.002) based diets. Tethered heifers fed the more fermentable and rapidly
      synchronized diet (barley-SFM) reduced intake and increased chewing time. With
      these high-concentrate diets, time spent chewing was inversely related to
      roughage intake.

PMID- 16612023
TI  - Wet corn gluten feed and alfalfa hay levels in dry-rolled corn finishing diets:
      effects on finishing performance and feedlot nitrogen mass balance.
AB  - One-hundred ninety-two crossbred steers (initial BW = 351 +/- 11 kg) were used to
      determine the effects of removing alfalfa hay (AH) from dry-rolled corn-based
      diets containing wet corn gluten feed (WCGF) on animal performance and nutrient
      (N and OM) mass balance in open feedlot pens. Steers were stratified by weight
      and assigned randomly to 24 pens (2 x 3 factorial) and fed for 132 d from June to
      October 2002. Experimental diets contained either 0 or 35% WCGF and 0, 3.75, or
      7.5% AH, and were formulated to be isonitrogenous. For efficiency of gain, an
      interaction occurred (P = 0.09) between AH and WCGF. Feed efficiencies of cattle
      fed 35% WCGF were improved 4.4% (P = 0.10) compared with efficiencies of cattle
      fed no WCGF at 0% AH; there was a marked improvement in ADG for cattle fed WCGF
      compared with no WCGF in diets with 0% AH. Within 35% WCGF diets, efficiency
      decreased as AH inclusion increased (P = 0.06). Efficiency was equal across AH
      levels when 0% WCGF was fed; however, ADG was decreased when AH was removed.
      Interactions between AH and WCGF were not detected for other performance or
      carcass criteria; therefore, main effects of AH and WCGF are discussed. Daily
      intake, ADG, and HCW increased linearly (P < 0.05) as dietary AH level increased.
      Feeding 35% WCGF also resulted in greater DMI (P < 0.01) and a tendency for
      greater ADG and HCW (P < or = 0.10) compared with steers fed no WCGF.
      Interactions between AH and WCGF were not observed for feedlot N mass balance. As
      level of AH increased across diets, N intake, N retention, and N excretion
      increased (P < 0.05). Steers fed 35% WCGF consumed and excreted more N (P < 0.01)
      than those fed no WCGF. More manure DM (P = 0.11), OM, and N (P < 0.01) were
      removed from pens housing steers fed 35% WCGF as well as greater OM and N
      recovery in finished compost. More N (kilogram/steer) was also lost to
      volatilization as a result of greater N excretion when WCGF was fed. Expressed as
      a percentage of N excretion, loss of N from pens housing steers fed 0 and 35%
      WCGF was not different, averaging nearly 80%. These data suggest that AH has less
      value when dry-rolled corn-based diets contain 35% WCGF and can be decreased from
      conventional levels. Furthermore, loss of N from open feedlot pens is high during
      the summer months, and feeding WCGF may not reduce N losses during these times of
      year.

PMID- 16612024
TI  - Determination of parotid sulfate secretion in sheep by means of ultrasonic flow
      probes.
AB  - The bilateral output of sulfate in parotid saliva, the relationship with its
      plasma level and with parotid flow, and its variation according to feeding
      behavior were determined in ad libitum, normal-sulfate (0.28% DM)-fed sheep (n =
      6) using a transit time ultrasonic flow meter system to measure salivary flow.
      Ultrasonic flow meter probes were bilaterally implanted, under general
      anesthesia, around parotid ducts previously fitted through their oral ends with
      nonobstructive sampling catheters. Salivary flows were continuously recorded
      during 24 h, and saliva and blood samples for sulfate determinations were
      obtained hourly. Jaw movements were monitored with the submandibular balloon
      technique. The sulfate concentration in parotid saliva (mean of the group = 4.9
      +/- 3.7 microg/mL) showed high variability between sheep (individual means from
      0.4 +/- 0.3 to 9.3 +/- 5.9 microg/mL) and averaged 12.3% of the more stable
      plasma level (41.2 +/- 8.1 microg/mL). Pronounced intraindividual variations were
      also evident (0.1 to 26.3 microg of sulphate/mL of parotid saliva), in strong
      association with the fluctuations of salivary output. In 4 sheep, a decreasing
      exponential relationship was observed between parotid sulfate concentration and
      salivary secretion rate (r2 = 0.36, P < 0.01). This fact and the absence of a
      relationship between sulfate levels in plasma and in saliva suggest a sulfate
      secretory process during the passage of primary saliva through the ductal tree of
      the gland. The greatest rates of bilateral salivary sulfate output were observed
      during feeding (14.1 +/- 14.0 microg/min) and rumination (12.7 +/- 11.0
      microg/min). Nevertheless, 49% of the sulfate output in parotid saliva was
      present during rest, as a result of the length of the resting times. The
      contribution of parotid sulfate to the ruminal S pool was highly variable and
      averaged 13.2 mg/d, representing less than 1% of the S intake. In conclusion, the
      accurate, reliable, nonobstructive, and bilateral salivary flow monitoring, using
      a previously characterized ultrasonic flow meter technique, allowed a detailed
      determination of the secretory dynamics of sulfate in parotid saliva, without
      disturbing the animal's routine or altering the physiological regulation of
      salivary output. The results indicated that, in the absence of S deficiency, the
      recycling of sulfate via saliva seems not to be a major factor in sheep
      nutrition.

PMID- 16612025
TI  - Consumer sensory acceptance and value of wet-aged and dry-aged beef steaks.
AB  - To determine sensory preference and value of fresh beef steak differing in aging
      technique, strip steaks were evaluated by consumers in Denver (n = 132 consumers)
      and Chicago (n = 141 consumers). Wet-aged Choice strip loins were matched with
      dry-aged Choice strip loins, whereas wet-aged Prime strip loins were matched with
      dry-aged Prime strip loins. Dry-aged strip loins were commercially aged in air in
      a controlled environment for 30 d and vacuum-aged for 7 d during shipping and
      storage. Wet-aged strip loins were vacuum-packaged and aged for 37 d in a 1
      degrees C cooler. Pairs of strip loins were matched to similar Warner-Bratzler
      shear force values and marbling scores. Twelve sensory evaluation panels (of 12
      scheduled panelists each) were conducted over a 3-d period in each city.
      Individual samples from a pair of steaks were evaluated by the panelists for
      sensory traits. Bids were placed on the samples after sensory traits were
      obtained utilizing a variation of the Vickery auction with silent, sealed bids.
      No significant differences for sensory traits of flavor, juiciness, tenderness,
      or overall acceptability were detected between wet-aged Choice samples and dry
      aged Choice samples. Although wet-aged Choice samples were numerically superior
      for all sensory traits, consumers placed similar bid values (P = 0.12) on wet-
      and dry-aged Choice samples ($3.82 per 0.45 kg and $3.57 per 0.45 kg,
      respectively). Wet-aged Prime samples were rated more desirable (P < 0.001) for
      flavor, tenderness, and overall acceptability than dry-aged Prime samples. Wet
      aged Prime samples were valued at $4.02 per 0.45 kg, whereas dry-aged Prime
      samples brought $3.58 per 0.45 kg (P = 0.008). Consumers (29.3%) who preferred
      the dry-aged Choice samples over the wet-aged Choice samples were willing to pay
      $1.99/0.45 kg more (P < 0.001) for dry-aged samples. The consumers who preferred
      the wet-aged Choice over the dry-aged Choice samples (39.2%) were willing to pay
      $1.77/0.45 kg more (P < 0.0001). Consumers who preferred wet-aged Prime over dry
      aged Prime samples (45.8%) paid $1.92/0.45 kg more (P < 0.0001). Consumers who
      preferred dry-aged Prime samples (27.5%) were willing to pay $1.92/0.45 kg more
      than for the wet-aged Prime samples. Although more consumers preferred wet-aged
      samples, markets do exist for dry-aged beef, and consumers are willing to pay a
      premium for this product.

PMID- 16612026
TI  - Effects of boar presence on agonistic behavior, shoulder scratches, and stress
      response of bred sows at mixing.
AB  - The objective of this study was to determine the effects of boar presence on
      aggression, shoulder scratches, and salivary cortisol in group-housed sows during
      the period after mixing, which is when dominance hierarchies are formed. A total
      of 225 York-shire sows were used. Five groups of 15 sows were each exposed to 1
      of 3 levels of boar presence (n = 15): physical (boar in pen with sows; 2.15 m2
      per sow), fenceline (boar housed adjacent to sows; 2.3 m2 per sow), or control
      (no boar in the room; 2.3 m2 per sow). The experiment was divided into 2 phases.
      In phase 1, behavioral measurements were taken for 48 h after mixing and boar
      introduction. In phase 2, behavioral measurements were taken beginning on d 6
      after mixing and included 24 h before and 48 h after boar removal. In phases 1
      and 2, shoulder scratches were scored 24 h before and 24 h after mixing and boar
      removal, respectively. Saliva samples were collected each morning (0600 to 0700)
      and afternoon (1600 to 1700) during both phases. Frequencies of intersow
      aggressive contact (bite, body knock, and head knock) and threats as well as
      frequencies and durations of fighting bouts were determined from video recordings
      during daily feeding (49.6 +/- 1.4 min) and nonfeeding (21 +/- 0.2 h) periods.
      During phase 1, boar presence did not affect the frequency of threats during
      either the feeding or nonfeeding periods. Control groups had fewer aggressive
      contacts at feeding during the 25- to 48-h period compared with the fenceline
      groups (P = 0.01). Total duration of fighting and average fighting bout duration
      were unaffected by treatment. However, the number of fights occurring during
      feeding 25 to 48 h postmixing was lower in the physical groups than in the
      fenceline groups (P = 0.023); measures for the control groups were intermediate.
      Physical sows also received fewer shoulder scratches postmixing than did control
      sows (P = 0.048). After mixing, physical sows showed greater morning (P = 0.08)
      and afternoon (6 h postmixing, P = 0.01; 32 h postmixing, P = 0.08) salivary
      cortisol concentrations compared with fenceline sows, although they were only
      numerically greater than those for control sows. During phase 2, removing the
      boar did not increase fighting among sows or affect shoulder scratches or
      salivary cortisol concentrations. The presence of a boar was minimally effective
      at reducing fighting and scratches during the postmixing period, and sows showed
      a greater stress response in the presence of a boar.

PMID- 16612027
TI  - Thermal balance of cattle grazing winter range: model application.
AB  - Beef cattle grazing semiarid foothill rangeland of the Northern Rockies during
      winter may be exposed to cold temperatures and high winds while grazing pastures
      with low nutritional value. Cattle can physiologically and behaviorally respond
      to the changing environment to lower their metabolic requirements and reduce the
      effects of cold exposure. Requirements of grazing cattle may be overpredicted
      with models developed in controlled settings that do not account for energy
      conserving behaviors. We refined a simple thermal balance equation to model heat
      exchange of free-ranging cattle. We accounted for the complex interactions
      between animal behavior and the changing natural environment by applying the
      insulation characteristics of the cattle's tissue and coat to a simple geometric
      shape of an asymmetric ellipsoid at different orientations to the sun and wind.
      We compared the model predictions with heat production measured in 3 studies, and
      in all cases the model predictions were similar to those reported. Model
      simulations indicate behaviors, such as lying and orientation to the sun,
      mitigated the effects of extreme weather. For many combinations of winter weather
      variables, metabolic requirements increased only slightly due to cold exposure of
      mature beef cattle in a near-maintenance state. The results indicate that solar
      radiation contributes strongly to the thermal balance of a cow. Thus, previous
      models that do not account for the irradiative environment may overestimate
      metabolic requirements of cattle acclimated to grazing winter range.

PMID- 16612028
TI  - Technical note: a monoclonal antibody-based immunoassay for determination of
      ractopamine in swine feeds.
AB  - An ELISA was developed for routine screening of ractopamine in swine feeds. Swine
      feed samples were extracted and purified, and the aqueous portion of the extract
      was analyzed for ractopamine using ELISA and confirmed by HPLC. For swine complex
      feeds containing ractopamine at 2.5 to 40 mg/kg, the average recoveries ranged
      from 73.1 to 86.5% by ELISA and 81.9 to 98.2% by HPLC. For the swine supplement
      containing ractopamine at 50 to 400 mg/kg, the average recoveries were 105.5 to
      111.4% by ELISA and 89.1 to 92.9% by HPLC. The limit of detection was 0.24
      microg/g by ELISA and 0.48 microg/g by HPLC, respectively. Results from the swine
      complex feeds (P = 0.009) and the supplement (P = 0.005) using ELISA and HPLC
      were not highly correlated. The ELISA was more sensitive and rapid and less
      expensive than the HPLC method and could be used for ractopamine screening in
      swine feeds before confirmation and quantification by other methods, such as
      HPLC.

PMID- 16612029
TI  - Differential effects of sodium and magnesium sulfate on water consumption by beef
      cattle.
AB  - The existing guidelines for maximum sulfate (SO4) in cattle drinking water are
      based on Na2SO4, although many water sources contain greater concentrations of
      MgSO4. Two experiments compared the effect of different SO4 salts on water
      consumption and fecal DM of cattle. In Exp. 1, 8 yearling heifers (initial BW =
      345 +/- 8 kg; mean +/- SD) were watered twice daily with tapwater or water
      containing Na2SO4 or MgSO4 at target levels of 1,500, 3,000, or 4,500 mg of SO4/L
      for 2-d treatment periods separated by 2 d of access to tapwater. In Exp. 2, 16
      yearling cattle (initial BW = 421 +/- 24 kg) were watered twice daily with tap
      water (16 mg of SO4/L) or water containing Na2SO4 at target levels of 2,000 mg of
      SO4/L (low Na2SO4), MgSO4 at 2,000 mg of SO4/L (low MgSO4), or MgSO4 at 4,000 mg
      of SO4/L (high MgSO4) in 21-d treatment periods separated by 7-d periods on
      tapwater. The first 10 d of each period were allowed for adjustment to the
      treatment, and the final 11 d was considered the treatment period for analysis
      purposes. Treatments were applied in an incomplete Latin square, where each
      animal was exposed to 3 of the 4 treatments. In Exp. 1, the average daily water
      consumption decreased linearly as the SO4 concentration increased for MgSO4 (P =
      0.0001) but not for Na2SO4 (P = 0.39). In Exp. 2, the average daily water
      consumption was less for cattle on the high-MgSO4 treatment than for cattle on
      the low-MgSO4 treatment (P = 0.0001), and cattle on the low-MgSO4 treatment
      tended (P = 0.09) to drink less than those on the tap-water treatment. Fecal DM
      was greater for cattle on the high-MgSO4 treatment than for those on the low
      MgSO4 treatment (P < 0.01). These findings indicate that cattle reduce their
      consumption of water containing high (> or = 4,000 mg of SO4/L) concentrations of
      MgSO4, even after a given time to adjust to the treatment; such reductions may be
      accompanied by an increase in fecal DM.

PMID- 16612030
TI  - Examination of potential methods to predict pulmonary arterial pressure score in
      yearling beef cattle.
AB  - Susceptibility of beef cattle to high altitude disease (HAD) is of major
      importance to economic and genetic selection on high elevation ranches. However,
      currently the best indicator of HAD susceptibility is the pulmonary arterial
      pressure (PAP) test, a test with high cost and invasive nature. Therefore, 2
      experiments were undertaken to determine whether emerging technologies that
      predict blood components could be used to predict the PAP score in yearling Angus
      cattle. In Exp. 1, 39 yearling Angus bulls were used to determine if a
      relationship existed between PAP score and 10 blood components provided by a
      hemogram using whole blood or oxygen saturation as predicted by pulse oximetry in
      nonanesthetized cattle measured rectally or orally. Three of the hemogram values
      (packed cell volume, hemoglobin concentration, and red cell distribution width)
      were correlated (P < 0.10) with the PAP score. Prediction equations for PAP score
      were generated using the hemogram values and resulted in R2 values of 0.375 and
      0.305 for the regression model using all of values and the best 2-variable model,
      respectively. Pulse oximetry was able to provide oxygen saturation predictions
      rectally or orally; however, the predicted values were not correlated with the
      PAP score (P > 0.10) or with each other (P > 0.10). In Exp. 2, 84 yearling Angus
      cattle (62 bulls, 22 heifers) were used to evaluate the ability of a portable
      clinical analyzer to predict the PAP score using 11 blood components from a
      sample of whole blood evaluated at the processing chute. The portable clinical
      analyzer was able to provide values for all of the 11 blood components; however,
      none of the predicted values were correlated with the PAP score (P > 0.10). In
      these preliminary experiments, 3 blood component values provided via the hemogram
      were the only variables both correlated with the PAP score and able to contribute
      to the development of a useful PAP prediction equation that could reduce the cost
      of traditional measures of HAD susceptibility. Future research is needed to
      determine whether additional blood components or emerging blood analysis
      technologies are able to accurately predict the PAP score in beef cattle.

PMID- 16612031
TI  - Evaluation in Appalachian pasture systems of the 1996 (update 2000) National
      Research Council model for weaning cattle.
AB  - This study was conducted to evaluate the accuracy of the National Research
      Council's (2000) Nutrient Requirements of Beef Cattle computer model when used to
      predict calf performance during on-farm pasture or dry-lot weaning and
      backgrounding. Calf performance was measured on 22 farms in 2002 and 8 farms in
      2003 that participated in West Virginia Beef Quality Assurance Sale marketing
      pools. Calves were weaned on pasture (25 farms) or dry-lot (5 farms) and fed
      supplemental hay, haylage, ground shell corn, soybean hulls, or a commercial
      concentrate. Concentrates were fed at a rate of 0.0 to 1.5% of BW. The National
      Research Council (2000) model was used to predict ADG of each group of calves
      observed on each farm. The model error was measured by calculating residuals (the
      difference between predicted ADG minus observed ADG). Predicted animal
      performance was determined using level 1 of the model. Results show that, when
      using normal on-farm pasture sampling and forage analysis methods, the model
      error for ADG is high and did not accurately predict the performance of steers or
      heifers fed high-forage pasture-based diets; the predicted ADG was lower (P <
      0.05) than the observed ADG. The estimated intake of low-producing animals was
      similar to the expected DMI, but for the greater-producing animals it was not.
      The NRC (2000) beef model may more accurately predict on-farm animal performance
      in pastured situations if feed analysis values reflect the energy value of the
      feed, account for selective grazing, and relate empty BW and shrunk BW to NDF.

PMID- 16612032
TI  - Hormonal profiles, behavioral responses, and short-term growth performance after
      castration of pigs at three, six, nine, or twelve days of age.
AB  - The objective of this study was to determine the effects of castration on short
      term growth performance, hormone profiles, and behavior in pigs at 3, 6, 9, or 12
      d of age. Ninety intact male pigs were assigned randomly to a treatment age by
      litter [3, 6, 9, or 12 d of age; n = 9 to 13 pigs per treatment (age) group].
      Pigs within a single litter were then assigned to noncastrated (NC) or castrated
      (CAS) treatment groups according to BW. Pigs were nonsurgically fitted with
      jugular catheters, and blood samples were drawn immediately before castration (0
      h) and at 0.5, 1, 1.5, 2, 24, and 48 h after castration. Body weights were
      obtained when pigs were catheterized and again at 24 and 48 h after castration.
      Serum samples were analyzed for cortisol, porcine corticosteroid-binding
      globulin, and dehydroepiandrosterone sulfate (DHEA-S). No differences were
      detected in initial BW of pigs, and there was no overall treatment effect on
      growth performance of pigs at 24 or 48 h posttreatment. A time x treatment
      interaction was detected (P < 0.01) for serum cortisol concentrations, such that
      cortisol was greater in CAS pigs than in NC pigs. No overall effect of age at
      castration was observed on cortisol concentrations. At 24 h after castration,
      serum cortisol concentrations returned to baseline in all treatment groups;
      however, at 48 h after castration, overall cortisol concentrations were elevated
      (P < 0.01) in the 6-, 9-, and 12-d-old pigs in both the CAS and NC groups
      compared with baseline concentrations. Total cortisol and porcine corticosteroid
      binding globulin were used to calculate the free cortisol index (FCI). A time x
      treatment interaction was observed (P < 0.01) for FCI, such that FCI was greater
      in CAS males than in NC males. The FCI was also affected by age (P < 0.01). There
      was a time x treatment x age interaction (P < 0.01) for serum DHEA-S, such that
      DHEA-S concentrations decreased in CAS animals but increased in NC animals, and
      DHEA-S concentrations increased with age. During the first 2 h after castration,
      there was an overall age effect (P = 0.01) on the time that pigs spent standing,
      such that 3-d-old pigs stood more than 6-, 9-, or 12-d-old pigs. Treatment did
      not influence the time that pigs spent nursing, lying, standing, or sitting,
      although there was a trend (P = 0.08) for CAS pigs to be less active than NC
      pigs. These data indicate that castration is stressful regardless of age;
      however, the stress associated with handling seems to increase as pigs age.

PMID- 16612033
TI  - Genomic analysis of the impact of fescue toxicosis on hepatic function.
AB  - Fescue toxicosis is caused by consumption of toxins produced by an endophytic
      fungus, Neotyphodium coenophialum, in tall fescue [Lolium arundinaceum (Schreb.)
      Darbysh]. Microarray analysis was used to identify shifts in genetic expression
      associated with the affected physiological processes to identify potential
      targets for future pharmacological/toxicological intervention. Male rats (n = 24)
      were implanted with temperature transmitters, which measure core temperature
      every 5 min. After an 8-d recovery, the rats were fed an endophyte-free diet for
      5 d. During the following 5-d treatment period, rats were fed either an endophyte
      free or an endophyte-infected (91.5 microg of ergovaline.kg of BW(-1).d(-1))
      diet. At the end of treatment, rats were euthanized and a sample of the liver was
      obtained. Feed conversion efficiency was calculated for both treatment groups.
      Serum prolactin concentrations were measured using ELISA. Liver tissue RNA was
      reverse transcribed and hybridized to an oligonucleotide microarray chip.
      Microarray data were analyzed using a 2-step ANOVA model and validated by
      quantitative real-time PCR. Significant reductions in mean core temperature, feed
      intake, feed conversion efficiency, BW, liver weight per unit of BW, and serum
      prolactin concentrations were observed in endophyte-infected rats. There was
      downregulation (P < 0.05) of various genes associated with energy metabolism,
      growth and development, and antioxidant protection, as well as an upregulation of
      genes associated with gluconeogenesis, detoxification, and biotransformation.
      This study demonstrated that even short-term exposure of rats to tall fescue
      endophytic toxins under thermoneutral conditions can result in physiological
      responses associated with altered gene expression within the liver.

PMID- 16612034
TI  - Simultaneous and minimally invasive assessment of muscle tolerance and
      bioavailability of different volumes of an intramuscular formulation in the same
      animals.
AB  - Evaluation of skeletal muscle tolerance during development of new drug
      formulations for i.m. use is most often based on terminal methods performed in
      the target species after slaughtering. The objective of this study was to
      evaluate the effect of muscle damage on the pharmacokinetic parameters of the
      drug delivered into the muscle using an alternative, noninvasive method.
      Phenylbutazone (PBZ) was used as the test article. Six ewes received increasing
      volumes of a 20% PBZ i.m. formulation, according to a cross-over design, and an
      i.v. bolus of the same formulation. Serial blood samples were taken, and a
      pharmacokinetic analysis of the plasma activity of creatine kinase and plasma PBZ
      concentrations was carried out. The amount of muscle damage after i.m.
      administration of 2, 4, or 8 mL of PBZ, calculated from the area under the curve
      of plasma creatine kinase across time was 36, 76, and 178 g for a 70-kg ewe. The
      corresponding absolute bioavailability of PBZ was 100 +/- 32%, 96 +/- 19%, and
      100 +/- 17%, and the maximal PBZ concentrations were 42 +/- 3.4, 74 +/- 8.8, and
      119 +/- 18.2 microg/mL. The plasma clearance of PBZ (i.v.) was 4.2 +/- 0.94
      mL.kg(-1).h(-1). In conclusion, the absolute bioavailability of PBZ after i.m.
      administration was not altered by the increased volume of formulation
      administered despite the overall increase in the extent of muscle damage.

PMID- 16612035
TI  - Effects of glutaraldehyde exposure on human health.
AB  - Glutaraldehyde (GA) is widely used in the industrial, scientific and biomedical
      fields. Many adverse health effects on humans have been reported in association
      with biomedical uses of GA, with 2-3.5% aqueous GA solution generally used for
      cold sterilization and GA exposure ranges of 0.001 to 2.6 ppm for this type of
      use. GA is metabolized extensively to CO(2), but urinary excretion of it is low.
      Sensory irritant effects, sensitization of skin and respiratory organs and other
      symptoms have been reported among endoscopy nurses and medical radiation
      technologists. The prevalence of chronic bronchitis and nasal symptoms in humans
      is significantly correlated with peak concentrations of GA exposure. The extent
      of primary skin irritation depends on the duration and site of contact, and the
      severity of symptoms is dose-related. Chronic inhalation affects the nose and
      respiratory tract, and lesions become severe with prolonged duration of exposure.
      Increases in neither mortality nor tumor incidence have been found in workers
      with less than 0.2 ppm GA exposure, no evidence of carcinogenic activity has been
      obtained in experimental animal studies. There has been no clear evidence of
      genetic toxicity of GA in either in vitro or in vivo studies, and neither
      developmental nor reproductive toxicity has been found in humans or animals. To
      prevent hazards from GA exposure, use of closed-system, fully automated washing
      machines is recommended, since numerous symptoms have been found in individuals
      with less than 0.05 ppm GA exposure, the recommended peak exposure limit in many
      countries.

PMID- 16612036
TI  - Hazards of X-ray radiation on the quantitative and phagocytic functions of
      polymorphonuclear neutrophils in X-ray technicians.
AB  - Over exposure to X-ray radiation is detrimental to the living cells and may lead
      to development of life-threatening diseases. It is intuitive to postulate that a
      low level exposure may lead to functional abnormalities in human immune cells.
      Therefore, the objective of the present study was to study the effects of X-ray
      radiation on the total leukocyte count (TLC) and phagocytic activity of
      Polymorphonuclear neutrophils (PMN). A group of 42 apparently healthy X-ray
      technicians were recruited with age ranging from 25-50 years. They were matched
      with another group of 42 control healthy volunteer subjects in terms of age, sex
      and ethnic variation. The mean exposure level of X-ray radiation in X-ray
      technicians was 72.4 mrem per calendar quarter and 289.6 mrem per year. TLC was
      performed by using a Beckman Coulter counter and phagocytic activity of whole
      blood and PMN was determined by measuring chemiluminescence (CL) response with a
      chemiluminescence luminometer. The mean value of CL response was significantly
      decreased (p<0.0005) in X-ray technicians, even though they had low levels of
      exposure, compared to their controls. However, no significant difference was
      observed in TLC between the two groups at this low level of exposure. Exposure to
      X-ray radiation decreases the physiological functions of PMN as measured by
      decreasing chemiluminescence response even at low levels of exposure.

PMID- 16612037
TI  - DNA lesion and Hprt mutant frequency in rat lymphocytes and V79 Chinese hamster
      lung cells exposed to cadmium.
AB  - Cadmium is a potential carcinogenic environmental and occupational pollutant. A
      wide variety of mutagens have been shown to cause DNA damage, but it is not yet
      clear whether the DNA damage is relative to inducement of mutations. DNA damage
      and the formation of mutations at the hypoxanthine guanine phosphoribosyl trans
      ferase (HPRT) induced by cadmium chloride (CdCl(2)) were investigated with rat
      lymphocytes and V79 Chinese hamster lung cells. The hprt mutant frequency (MF)
      assay was used as the method to measure gene mutation in the rat lymphocytes and
      V79 cells exposed to CdCl(2), and comet assay analysis was performed to detect
      DNA lesion and repair in CdCl(2)-induced V79 cells. The results showed that
      CdCl(2) treatment caused a strong genotoxic effect and a marginal effect on the
      frequency of gene mutations. The hprt mutant frequencies in the rat lymphocytes
      and V79 cells exposed to CdCl(2) were statistically higher than those of the
      negative control. There was statistical significance in TL, TD and percentage of
      comet cell with tails. CdCl(2) treatment can induce DNA single-strand breaks.
      There was a dose-dependent increase between CdCl(2) and DNA lesion. After cells
      were treated with CdCl(2) and hydrogen peroxide (H(2)O(2)), the TL and TD
      declined with repair time increasing, which indicated that DNA damages were
      repaired gradually. However, DNA repair with treatment of CdCl(2) was slower than
      that of H(2)O(2) in V79 cells, which suggests that CdCl(2) affected DNA repair of
      damaged cells. The study also showed that the hprt MF and comet assay can be used
      for genotoxicity testing of heavy metals. DNA damage detected with the comet
      assay may be relative to mutagenesis.

PMID- 16612038
TI  - The effect of occupational exposure to metals on the nervous system function in
      welders.
AB  - We explored the relationship between metals exposure and nervous impairment in
      welders. The metals exposure of 82 welders and 51 operators were evaluated for
      blood Pb, Cd and Mn by atomic absorption spectrometry, and the nervous system
      impairment was evaluated with the neurobehavioral core test battery and
      electromyography. Pb (geometric mean: 117.31 mug/L; range: 0.5-327.6 mug/L) and
      Cd (geometric mean: 3.54 mug/L; range: 0.2-12.5 mug/L) in welders were
      significantly higher than those in operators. Welders had higher prevalence of
      nervous system symptoms and worse standard scores of 8 items such as depression
      dejection than operators. Significant difference of nervous performance in
      welders only existed in different concentration groups of Pb and Mn. The
      performances of fatigue-inertia and some others had negative correlations with Pb
      and digit span with Mn. Therefore, the nervous system impairment in welders could
      be attributed to occupational exposure of Pb and Mn, but not Cd, concomitantly.

PMID- 16612039
TI  - Visual display terminal work and sick building syndrome--the role of psychosocial
      distress in the relationship.
AB  - The present study investigated the association between visual display terminal
      (VDT) work and sick building syndrome (SBS) and the role of psychosocial factors
      in the relationship. Subjects were 2,161 Japanese office workers who responded to
      a cross-sectional anonymous self-administered questionnaire survey. Questions
      included were derived from the Miljomedicin 040, a validated questionnaire on SBS
      symptoms. After exclusion of data with missing information, data for 1,881
      subjects were used for analysis. Multivariate logistic regression was used to
      estimate the odds ratio for SBS with adjustment for potential confounding
      factors, including psychosocial work stress. In multivariate analysis, the odds
      ratio for SBS was significantly elevated for men engaged in VDT work for 4 or
      more hours a day (OR=2.5, 95%CI: 1.0, 5.9) compared with less than 1 hour a day,
      showing a significant trend association (P for trend=0.04). In women, although
      the odds ratio for SBS with VDT use of 4 or more hours a day was somewhat
      elevated with adjustment for non-psychosocial factors (OR=1.5, 95%CI: 0.5, 4.3),
      the increase was greatly attenuated after adjustment for psychosocial work
      distress (OR=1.1). In conclusion, our study suggests that extended hours of VDT
      use might be related to increased SBS symptoms. Moreover, psychosocial distress
      related to VDT work might mediate the relationship between VDT use and SBS
      symptoms in women.

PMID- 16612040
TI  - Mental and physical effects of Tanshin funin, posting without family, on married
      male workers in Japan.
AB  - This paper investigates the effects of tanshin funin, a posting without family,
      on the health of married male workers. A prospective study using the pair-matched
      method was performed. One hundred and twenty-nine married male tanshin funin
      workers in their 40s and 50s and as many matched workers living with their family
      (regular workers) participated. Fewer tanshin funin workers took breakfast
      everyday (OR=3.3, p<0.001). Tanshin funin workers more frequently suffered from
      stress due to daily chores (OR=3.6, p<0.001) and from stress-related health
      problems, namely headache (OR=4.7, p=0.013) and gastric/duodenal ulcers (OR=8.7,
      p<0.001). They also developed more frequently common cold/bronchitis (OR=14.5,
      p<0.001). The levels of gamma-glutamyl transpeptidase for workers reluctant to
      work under tanshin funin and workers who spent less than two years in tanshin
      funin increased significantly from the fiscal year 1997 to year 2001 (46.7 to
      67.5 IU/l, p<0.001, and 36.9 to 72.4 IU/l, p=0.005, respectively), although those
      of their matched regular workers did not show significant changes. The daily
      alcohol intake of reluctant tanshin funin workers (the equivalent of
      approximately 817 ml of beer) was higher than that of the matched regular workers
      (582 ml, p=0.026). In summary, abrupt changes in lifestyle and elevated mental
      stress were thus important effects of tanshin funin. Tanshin funin workers should
      be provided with health and lifestyle education programs and mental health care
      before and during tanshin funin. Doctors and nurses in the healthcare departments
      of companies should play a leading role.

PMID- 16612041
TI  - Expression of heme oxygenase-1 in the lungs of rats exposed to crystalline
      silica.
AB  - Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced
      by particles, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative
      stress. We hypothesized that HO-1 is also associated with oxidative lung injury
      caused by exposure to particles. The present study was conducted to investigate
      the time course of HO-1 expression of lungs exposed to crystalline silica in
      vivo. Male Wistar rats were administered 1 mg or 2 mg of crystalline silica
      suspended in saline by a single intratracheal instillation and were sacrificed at
      3 d, 1 wk, 1 month, 3 months and 6 months of recovery time. The expression of HO
      1 was observed by western blot analysis and immunostaining. Protein levels of HO
      1 were increased compared to the controls at 3 d, and from 1 month to 6 months
      following intratracheal instillation of 2 mg of crystalline silica. The levels of
      HO-1 were increased compared to the controls from 1 month to 6 months following
      intratracheal instillation of 1 mg of crystalline silica. Many HO-1 positive
      cells were found particularly in the alveolar macrophages during immunostaining.
      These findings suggest that HO-1 is related to lung injury arising from exposure
      to crystalline silica.

PMID- 16612042
TI  - Three occupationally exposed cases of severe methyl bromide poisoning: accident
      caused by a gas leak during the fumigation of a folklore museum.

PMID- 16612043
TI  - Two new criteria of the metabolic syndrome: prevalence and the association with
      brachial-ankle pulse wave velocity in Japanese male workers.
AB  - In 1998 and 2001, The World Health Organization and the National Cholesterol
      Education Program Adult Treatment Panel III proposed working criteria for the
      metabolic syndrome (MS), but they are not perfect for use in diverse ethnicities.
      In 2005, the International Diabetes Federation (IDF) and eight societies in Japan
      respectively proposed new criteria. However, there has been no report regarding
      the application of these new criteria in Japanese workplaces. We conducted a
      cross-sectional study of 377 healthy Japanese men aged 20-64 yr who worked in a
      chemical factory in Kanagawa, Japan. Participants completed a self-reported
      questionnaire, underwent a physical examination including waist measurements and
      brachial-ankle pulse wave velocity (baPWV), and provided overnight fasting blood
      samples. The prevalence of MS in Japanese men was 17.0% and 13.5% according to
      the new IDF and Japanese criteria respectively. In both of the new criteria,
      baPWV was significantly higher in those with MS than those without MS (1,563 +/-
      264.2 vs 1,362 +/- 204.6 cm/sec, p<0.001 in the new IDF criterion; 1,574 +/-
      265.2 vs 1,368 +/- 209.1 cm/sec, p<0.001 in the Japanese criterion). In the
      analysis of the 5 or 6 subgroups stratified according to the number of MS
      components, baPWV increased significantly with increasing number of MS components
      (p for trend<0.01 in both criteria). The new IDF and Japanese criterion are both
      good for diagnosing MS among Japanese because a linear increase in baPWV occurred
      with increasing MS components after adjustment for potential confounding factors.
      Further studies are expected using these new criteria.

PMID- 16612044
TI  - Impact of acute coronary syndrome (ACS) on work-relatedness evaluation in
      cerebrovascular and cardiovascular diseases among workers.

PMID- 16612045
TI  - Biological, physiological, and pharmacological aspects of ghrelin.
AB  - Ghrelin, identified as an endogenous ligand for the growth hormone secretagogue
      receptor, functions as a somatotrophic and orexigenic signal from the stomach.
      Ghrelin has a unique post-translational modification: the hydroxyl group of the
      third amino acid, usually a serine but in some species a threonine, is esterified
      by octanoic acid and is essential for ghrelin's biological activities. The
      secretion of ghrelin increases under conditions of negative energy-balance, such
      as starvation, cachexia, and anorexia nervosa, whereas its expression decreases
      under conditions of positive energy-balance such as feeding, hyperglycemia, and
      obesity. In addition to having a powerful effect on the secretion of growth
      hormone, ghrelin stimulates food intake and transduces signals to hypothalamic
      regulatory nuclei that control energy homeostasis. Thus, it is interesting to
      note that the stomach may play an important role in not only digestion but also
      pituitary growth hormone release and central feeding regulation. We summarized
      recent findings on the integration of ghrelin into neuroendocrine networks that
      regulate food intake, energy balance, gastrointestinal function and growth.

PMID- 16612046
TI  - Cardiac adrenoceptors: physiological and pathophysiological relevance.
AB  - At present, nine adrenoceptor (AR) subtypes have been identified: alpha(1A)-,
      alpha(1B)-, alpha(1D)-, alpha(2A)-, alpha(2B)-, alpha(2C)-, beta(1)-, beta(2)-,
      and beta(3)AR. In the human heart, beta(1)- and beta(2)AR are the most powerful
      physiologic mechanism to acutely increase cardiac performance. Changes in betaAR
      play an important role in chronic heart failure (CHF). Thus, due to increased
      sympathetic activity in CHF, betaAR are chronically (over)stimulated, and that
      results in beta(1)AR desensitization and alterations of down-stream mechanisms.
      However, several questions remain open: What is the role of beta(2)AR in CHF?
      What is the role of increases in cardiac G(i)-protein in CHF? Do increases in G
      protein-coupled receptor kinase (GRK)s play a role in CHF? Does betaAR-blocker
      treatment cause its beneficial effects in CHF, at least partly, by reducing GRK
      activity? In this review these aspects of cardiac AR pharmacology in CHF are
      discussed. In addition, new insights into the functional importance of beta(1)-
      and beta(2)AR gene polymorphisms are discussed. At present it seems that for
      cardiovascular diseases, betaAR polymorphisms do not play a role as disease
      causing genes; however, they might be risk factors, might modify disease, and/or
      might influence progression of disease. Furthermore, betaAR polymorphisms might
      influence drug responses. Thus, evidence has accumulated that a beta(1)AR
      polymorphism (the Arg389Gly beta(1)AR) may affect the response to betaAR-blocker
      treatment.

PMID- 16612047
TI  - Relationship between symptoms and quality of life in a sarcoidosis population.
AB  - BACKGROUND: As sarcoidosis is a multisytemic disorder, patients may suffer from
      various symptoms. The relationship between frequently reported symptoms and
      quality of life (QOL) has not yet been studied. OBJECTIVES: The aim of the
      present cross-sectional study was to examine the predictive value of the most
      frequently reported subjective symptoms on QOL after controlling for demographic
      variables and clinical parameters. METHODS: A cross-sectional study was conducted
      at an outpatient pulmonary clinic in Zagreb, Croatia. One hundred and fifty
      outpatients with sarcoidosis were seen between January 2002 and May 2004.
      Symptoms were assessed with a symptom inventory questionnaire, and QOL was
      measured using the World Health Organization Quality of Life Assessment
      Instrument. Clinical parameters were derived from the patients' medical files.
      Regression analyses were performed to examine the predictive value of symptoms on
      QOL. RESULTS: The four most frequently mentioned symptoms were fatigue,
      breathlessness, reduced exercise capacity and arthralgia. In various
      combinations, being female, using corticosteroids and fatigue predicted the QOL
      domains physical and psychological health as well as level of independence.
      CONCLUSIONS: Fatigue appeared to be the most important symptom in predicting
      various QOL domains after controlling for demographics, disease stage and
      clinical parameters. Therefore, considering improvement in the patients' QOL, it
      is recommended to focus not only on objective health parameters, but also on
      fatigue in the management of sarcoidosis.

PMID- 16612048
TI  - Mechanics of respiratory muscles in single-lung transplant recipients.
AB  - BACKGROUND: Emphysema and pulmonary fibrosis force the patients to breathe at an
      abnormal lung volume, which alters the lengths of the respiratory muscles and
      thereby their work capability is reduced. After single-lung transplantation,
      muscle function is restored on the side of the transplant but it may be
      asymmetric to that on the side of the native diseased lung. OBJECTIVE:
      Investigating the hypothesis that single-lung transplantation induces mechanical
      asymmetry of the respiratory muscles on the two sides. METHODS: Simultaneously
      noninvasive measurements of inspiratory and expiratory mouth pressure, airflow
      rate and electromyography signals from the sternomastoid, external intercostal,
      rectus abdominis and external oblique muscles were acquired during different
      breathing maneuvers. The study group included 10 single-lung transplant
      recipients (5 with pulmonary fibrosis and 5 with emphysema) and 10 healthy
      controls. RESULTS: Analysis of the finding shows a significant lower global
      strength of the respiratory muscles of single-lung transplant recipients compared
      to that of healthy subjects. No significant difference in the EMG signals of
      respiratory muscles was found either between the different groups or between the
      sides of the transplant and the native lung in the patient groups. Both single
      lung transplant recipients and healthy subjects demonstrated high EMG activity of
      the inspiratory muscles during inspiration at different breathing efforts.
      CONCLUSION: Patients after single-lung transplantation have lower respiratory
      muscle strength than healthy subjects, but apparently normal electrical activity.
      The lower global respiratory muscle strength emphasizes the importance of their
      rehabilitation before and after single-lung transplantation.

PMID- 16612049
TI  - Rotation frequency of human bronchial and nasal epithelial spheroids as an
      indicator of mucociliary function.
AB  - BACKGROUND: We evaluated a new in vitro model for mucociliary transport function.
      Spheroids of human respiratory epithelium show beating cilia at their surface.
      When cultured in their own mucus, spheroids can rotate along their axis due to
      coordinated ciliary beating. OBJECTIVE AND METHODS: To assess whether this setup
      yields meaningful results we measured rotation frequency (RF) of human bronchial
      or nasal epithelial spheroids under different temperatures and concentrations of
      isoproterenol. Isoproterenol was administered either as caged compound releasing
      active isoproterenol after illumination with UV light, or through a permeable
      membrane in a two-chamber system. RESULTS: Under stable conditions, RF remained
      constant over 200 min. Between 27 and 35 degrees C, there was a temperature
      dependent increase: RF(27)( degrees )(C) = 0.27 +/- 0.08 s(-1), and RF(37)(
      degrees )(C) = 0.43 +/- 0.10 s(-1) (means +/- SEM). Isoproterenol (10(-5), 10(-4)
      and 10(-3) mmol/l) induced concentration-dependent increases in RF (9, 20 and
      25%, respectively; medians) if applied in the two-chamber system. The experiments
      with caged isoproterenol did not yield conclusive results, probably because the
      byproducts from photolysis negatively affected ciliary function. The transport
      velocity at the surface of bronchial and nasal spheroids was estimated to be 2.96
      and 3.62 mm/min (medians), respectively, which is in the same range as mucus
      transport velocity measured in vivo in humans. CONCLUSIONS: This setup can be
      used to study mucociliary transport function under controlled conditions in
      vitro, in particular as RF is likely to reflect not only ciliary beat frequency,
      but also the coordination of ciliary beating and the properties of the mucus.

PMID- 16612050
TI  - Evaluation of body fat changes during weight loss by using improved
      anthropometric predictive equations.
AB  - BACKGROUND/AIM: Skinfold-based equations are widely used to evaluate body fat
      (BF), but over-/underestimation is often reported. We evaluate the capacity of
      improved skinfold-based equations to estimate BF changes during weight reduction
      and compare them against well-established equations. METHODS: Overweight adults
      (n = 44) participated in a 4-month weight reduction intervention. Dual-energy X
      ray absorptiometry (DXA) and anthropometric measurements were taken at baseline
      and after intervention. The BF% was calculated using Garcia, Peterson, and Durnin
      and Womersley (DW) equations. RESULTS: Baseline and postintervention BF% measured
      by DXA correlated highest with BF% predicted according to Garcia (r = 0.934 and r
      = 0.948, respectively), followed by Peterson (r = 0.941 and r = 0.932,
      respectively) and DW (r = 0.557 and r = 0.402, respectively); only a slight
      systematic error in overestimating the BF% was observed in estimates according to
      Garcia (r = 0.147 and r = 0.104, respectively; p < 0.001), while increasing
      errors occurred using the Peterson (r = 0.624 and r = 0.712, respectively; p <
      0.001) and DW (r = 0.767 and r = 0.769, respectively; p < 0.001) equations.
      Moderate correlations between BF changes (kg) measured by DXA and predicted by DW
      (r = 0.7211), Peterson (r = 0.697), and Garcia (r = 0.645) were observed.
      CONCLUSION: Improved skinfold equations cannot accurately measure changes in BF
      after weight reduction.

PMID- 16612051
TI  - Envelope following responses to natural vowels.
AB  - Envelope following responses to natural vowels were recorded in 10 normal hearing
      people. Responses were recorded to individual vowels (/a/, /i/, /u/) with a
      relatively steady pitch, to /[symbol: see text]/ with a variable and steady
      pitch, and to a multivowel stimulus (/[symbol: see text]ui/) with a steady pitch.
      Responses were analyzed using a Fourier analyzer, so that recorded responses
      could follow the changes in the pitch. Significant responses were detected for
      all subjects to /a/, /i/ and /u/ with the time required to detect a significant
      response ranging from 6 to 66 s (average time: 19 s). Responses to /[symbol: see
      text]/ and /[symbol: see text]ui/ were detected in all subjects, but took longer
      to demonstrate (average time: 73 s). These results support the use of a Fourier
      analyzer to measure envelope following responses to natural speech.

PMID- 16612052
TI  - Cancer and pregnancy share similar mechanisms of immunological escape.
AB  - BACKGROUND: Despite the fact that trophoblasts and cancer are both immunogenic,
      they are able to escape from host immunosurveillance, and the precise mechanisms
      involved in this process are surprisingly similar in both situations. METHODS: A
      literature review of studies on immunological changes occurring during normal
      pregnancy and cancer was performed. RESULTS: Loss or downregulation of classical
      HLA antigens as well as the presence of non-classical HLA-G molecules, a Th2
      cytokine activity shift, secretion of immunosuppressive factors and blocking
      antibodies and finally induction of apoptosis in immunocytes seem to be the most
      effective mechanisms of immunological escape in pregnancy and cancer.
      CONCLUSIONS: The process of immunological escape in cancer and pregnancy is based
      on similar mechanisms.

PMID- 16612054
TI  - Linezolid and human polymorphonuclear leukocyte function.
AB  - BACKGROUND: To examine whether linezolid, a new oxazolidinone antibiotic, has an
      effect on human polymorphonuclear leukocyte (PMN) function. METHODS: Flow
      cytometric techniques for the demonstration of PMN chemotaxis towards zymosan
      activated serum, and phagocytosis and respiratory burst after incubation in
      linezolid. RESULTS: Linezolid at concentrations of 10- 160 mg/l did not
      significantly influence PMN function as measured by chemotaxis, phagocytosis and
      respiratory burst. CONCLUSIONS: Linezolid at therapeutic or supratherapeutic
      concentrations does not influence human PMN function. This applies to the
      chemically pure substance as well as to the commercial preparation containing
      additives for intravenous infusion.

PMID- 16612053
TI  - Influence of sex on the pharmacokinetics of ciprofloxacin and ofloxacin.
AB  - The pharmacokinetics of orally administered ciprofloxacin and ofloxacin were
      studied in healthy volunteers to assess the influence of sex on drug
      bioavailability. The first group of subjects (9 males and 9 females) received a
      single oral dose of 200 mg ofloxacin, and the second group of volunteers included
      24 subjects (12 males and 12 females) treated with a single oral dose of 100 mg
      ciprofloxacin. Blood samples (3 ml) were collected and investigated in this
      parallel design study in both groups, and ciprofloxacin and ofloxacin
      concentrations were determined. These experimental data, which had not been
      changed by any mathematical operation, were collected and used to determine the
      effect of sex on the pharmacokinetic profile using parametric and non-parametric
      tests as well as multivariate classification tools like cluster analysis (CA) and
      principal component analysis (PCA). The following variables demonstrated
      significant differences (p < 0.05) in c(0.5), c(1.5), c(2.0), c(4.0), c(10),
      c(12.0), c(24) and c(6.0), c(8.0), c(10.0) for ofloxacin and ciprofloxacin,
      respectively, using Student's t test and ANOVA. Therefore the alternative
      hypothesis about sex differences between males and females was accepted. The CA
      and PCA plot separated females from males and allowed to select subjects
      accounting for differences between males and females. Data on the whole
      pharmacokinetic profile enabled to determine subtle sex differences between males
      and females.

PMID- 16612055
TI  - Molecular markers of multiple drug resistance in breast cancer.
AB  - Breast cancer is a significant health problem in terms of both morbidity and
      mortality, with approximately 12% of women directly affected by this disease.
      Chemotherapy, given to patients with earlier stage disease, has a good survival
      impact and may contribute to cure. The failure of chemotherapeutic drugs to
      eradicate cancer cells in more advanced disease states may be due to intrinsic or
      acquired drug resistance, including multiple drug resistance. The drug resistance
      observed in breast cancer patients is likely to be multifactorial, involving
      mechanisms such as altered expression and/or activity of drug efflux pumps,
      nuclear DNA-binding enzymes, metabolizing and conjugating enzymes, and mismatch
      repair deficiency. More extensive transcriptomic and proteomic analyses of breast
      tumour and normal biopsies, followed by functional genomic studies in relevant
      cell line models, should increase our understanding of this phenomenon and lead
      to therapies being individualized for identifiable subgroups of breast cancer
      patients.

PMID- 16612056
TI  - Human subjects, third parties, and informed consent: a brief historical
      perspective of developments in the United States.
AB  - The protection of human subjects in biomedical research has become a source of
      increasing concern over the past century. During the early days of human
      experimentation, the human subject was rarely if ever consulted about his or her
      participation in research because scientists and physicians acted in the
      traditional paternalistic role with respect to their subjects and patients.
      However, as options for both researchers and their subjects increased, more
      attention was focused on the rights and obligations of participants on both sides
      of the research relationship. Investigators became more aware of the costs and
      benefits associated with their research programs, and subjects became more
      curious about the nature of research and what could be reasonably expected from
      their participation. This paper reviews the evolution of the doctrine of informed
      consent in biomedical research and the development of rules and guidelines for
      the conduct of research in the United States, for the benefit of both researchers
      and their human subjects.

PMID- 16612057
TI  - How do women decide? Accepting or declining BRCA1/2 testing in a nationwide
      clinical sample in the United States.
AB  - OBJECTIVE: To examine the role of the practitioner, informed consent, and genetic
      counseling in genetic testing decisions and to assess their relative influence on
      women's decision to have clinical BRCA1/2 testing. METHODS: Qualitative study
      using in-depth open-ended interviews with 68 women who had considered clinical
      BRCA1/2 testing. RESULTS: Slightly less than half of the women who had considered
      BRCA1/2 testing were found to have had a clear and preexisting desire to test or
      not to test, irrespective of practitioner attitude or advice. CONCLUSION: The
      decision to accept or decline genetic testing is the result of a complex process
      that goes beyond interactions between health care providers and patients,
      indicating a caution against exclusive reliance on informed consent or counseling
      encounters.

PMID- 16612058
TI  - Analysis of co-aggregation of cancer based on registry data.
AB  - OBJECTIVE: An exploratory analysis of co-aggregation of cancers using registry
      based data. METHODS: We utilized sibships from over 18,000 families who had been
      recruited to the NCI-sponsored multi-institutional Cancer Genetics Network. The
      analysis assesses co-aggregation at the individual and family level and adjusts
      for ascertainment. RESULTS: We found statistically significant familial co
      aggregation of lung cancer with pancreatic (adjusted p < 0.001), prostate
      (adjusted p < 0.003), and colorectal cancers (adjusted p = 0.004). In addition,
      we found significant familial co-aggregation of pancreatic and colorectal cancers
      (adjusted p = 0.018), and co-aggregation of hematopoietic and (non-ovarian)
      gynecologic cancers (adjusted p = 0.01). CONCLUSION: This analysis identified
      familial aggregation of cancers for which a genetic component has yet to be
      established.

PMID- 16612059
TI  - Fourteen-year experience of prenatal diagnosis of thalassemia in Iran.
AB  - For 14 years, Iranian scientists have worked to develop a national thalassemia
      prevention program. Although historically abortion was considered unacceptable in
      Iran, intensive consultations led to the clerical approval of induced abortion in
      cases with beta-thalassemia major in 1997, and a nationwide prevention program
      with screening, counseling and prenatal diagnosis (PND) networks has been
      developed. This paper reports the experience from one of the two national PND
      reference laboratories. As one of the oldest reference laboratories, we performed
      a total of 906 PND in 360 couples at risk for thalassemia from 1990 to 2003.
      Direct and indirect mutation detection methods were applied for all cases. In
      total, 22 mutations were tested routinely, and an additional 30 rare mutations
      were identified. 208 fetuses were found to be normal, 215 fetuses had beta
      thalassemia major, and 435 fetuses were carriers of the trait. In 40 cases, we
      only defined one allele. In 8 cases, we were unable to provide any diagnosis,
      corresponding to 0.9%. Our data support the functionality of the Iranian beta
      thalassemia prevention program. The success of this system in Iran, a multiethnic
      and Islamic-based country, would mean that it might be applied as an adaptive
      system for neighboring and other Islamic countries.

PMID- 16612060
TI  - Economic evaluation of the familial cancer programme in Western Australia:
      predictive genetic testing for familial adenomatous polyposis and hereditary non
      polyposis colorectal carcinoma.
AB  - AIM: To evaluate costs and outcomes of genetic testing for familial colorectal
      cancer through services provided by Genetic Services of Western Australia (GSWA).
      METHODS: Costs and outcomes of predictive DNA-based testing for inherited
      colorectal cancers (CRC) were assessed, specifically for familial adenomatous
      polyposis (FAP) and hereditary non-polyposis CRC (HNPCC) using a decision
      analysis model. Costs were assigned according to standards of care in Western
      Australia (WA). Cancer risks and the efficacy of surveillance on long-term
      outcomes were derived from the published literature. RESULTS: The cost
      effectiveness of genetic testing was compared in first-degree relatives of known
      mutation carriers who have a 50% risk of carrying the mutated gene (intervention
      group) to individuals with the same risk but who do not undergo a genetic test
      (control subjects). Compared with control subjects undergoing the same high-level
      surveillance and surgery, the FAP and HNPCC intervention groups provided total
      savings of 13,390 US dollars and 14,783-15,460 per person (males-females),
      respectively. HPNCC mutation carriers also gained 1 CRC-free year. Compared to
      control subjects having only population surveillance, individuals in the FAP
      intervention group delayed the onset of CRC by 40 years for a net cost of 9,042
      US dollars. Individuals in the HNPCC intervention group delayed the onset of CRC
      by 8 years at a net cost of 12,141 US dollars for males and 12,596 US dollars for
      females. CONCLUSIONS: Genetic testing for familial CRC in WA allows targeted
      surveillance for mutation carriers, which ensures the efficient use of resources
      and reduces cancer-related morbidity, if clinical recommendations for
      intervention are adopted.

PMID- 16612061
TI  - Epidemiological characterization of congenital heart disease in Sao Miguel
      Island, Azores, Portugal.
AB  - OBJECTIVES: This study aimed to characterize the prevalence of congenital heart
      disease (CHD) in children born alive in Sao Miguel island from January 1992 to
      December 2001. METHODS: Based on the Azorean Registry of CHD, which includes
      complete clinical and personal information, 189 patients were diagnosed. RESULTS:
      During this 10-year period, the average prevalence of CHD is 9.16 per 1,000 live
      births (range 4.77-12.75). The most frequent cardiac malformations found were:
      ventricular septal defect (38.1%), atrial septal defect (12.2%) and patent ductus
      arteriosus (11.6%). Until now, four familial clusters were identified,
      representing a total of 13 patients. CONCLUSIONS: This first epidemiological
      study of CHD in the Azorean population reveals evidence for familial aggregation,
      which is of great interest for understanding the genes involved in these complex
      pathologies.

PMID- 16612062
TI  - Relationship of the sickle cell gene to the ethnic and geographic groups
      populating the Sudan.
AB  - The presence of a geographical pattern in the distribution of the sickle cell
      gene (S gene) and its association with malaria is well documented. To study the
      distribution of the S gene among various ethnic and linguistic groups in the
      Sudan we analyzed a hospital-based sample of 189 sickle cell anemia (SCA)
      patients who reported to the Khartoum Teaching Hospital between June 1996 and
      March 2000 and 118 controls with other complaints, against their ethnic and
      linguistic affiliations and geographic origin. Electrophoresis for hemoglobin S
      and sickling tests were carried out on all patients and controls as a
      prerequisite for inclusion. The majority of patients (93.7%) belonged to families
      of single ethnic descent, indicating the high degree of within-group marriages
      and thus the higher risk of augmenting the gene. SCA was found to be predominant
      among the Afro-Asiatic-speaking groups (68.4%) including nomadic groups of Arab
      and non- Arab descent that migrated to the Sudan in various historical epochs.
      Those patients clustered in western Sudan (Kordofan and Darfur) from where 73% of
      all cases originate. The proportion of patients reporting from other geographic
      areas like the south (3.1%), which is primarily inhabited by Nilo-Saharan
      speaking groups (19% of the whole sample) who populated the country in previous
      times, is disproportionate to their total population in the country (chi(2) =
      71.6; p = 0.0001). Analysis of the haplotypes associated with the S gene
      indicated that the most abundant haplotypes are the Cameroon, Benin, Bantu and
      Senegal haplotypes, respectively. No relationship was seen between haplotypes and
      the various hematological parameters in the sub-sample analyzed for such
      association. These results provide an insight into the distribution of the sickle
      cell gene in the Sudan, and highlight the strong link of the middle Nile Valley
      with West Africa through the open plateau of the Sahel and the nomadic cattle
      herders and also probably the relatively young age of the S gene.

PMID- 16612063
TI  - Hemoglobinopathy control program in Turkey.
AB  - Hemoglobinopathies are a very important health problem in Turkey. To date many
      studies have been performed but there has been no national hemoglobinopathy
      control program (HCP). After the Turkish National Hemoglobinopathy Council (TNHC)
      was created all centers, foundations, and associations were combined into one
      organization controlled by the Ministry of Health (MOH). The MOH and the TNHC
      have started to register the results of the screening of 377,339 healthy subjects
      from 16 different cities and the recorded average frequency of the beta
      thalassemia trait was 4.3%. The highest prevalence of thebeta-thalassemia trait
      (13.1%) was found in the Antalya region and of the HbS trait (10%) in the
      Cukurova region. Next, written regulations for the Fight against Hereditary Blood
      Disease were published especially for preventing and treating hemoglobinopathies.
      The MOH and the TNHC selected 33 provinces situated in the Thrace, Marmara,
      Aegean, Mediterranean and South Eastern regions with a high birth prevalence of
      severe hemoglobinopathies. The hemoglobinopathy scientific committee was set up,
      a guidebook was published and a national HCP was started in these high-risk
      provinces.

PMID- 16612064
TI  - Assessment of a pioneer metabolic information service in Brazil.
AB  - The Information Service on Inborn Errors of Metabolism (SIEM), a pioneer toll
      free service in both Brazil and South America, is based in Porto Alegre, Southern
      Brazil. SIEM has been operating since October 2001 providing support to health
      care professionals involved in the diagnosis and management of suspected
      metabolic diseases. We analyzed the demographic and clinical characteristics of
      the 376 consults received and followed in the first two and half years of SIEM.
      Our results show that the suspicion of a metabolic disease was most often
      associated with neurological symptoms. Among the consults, 24.4% were eventually
      confirmed as inborn errors of metabolism (IEM), with organic acidurias and amino
      acid disorders being the two most frequent diagnostic groups. Our conclusion
      shows this kind of service to provide helpful support to the diagnosis and acute
      management of IEM, especially to health professionals working in developing
      countries who are often far from reference centers.

PMID- 16612065
TI  - Changes in metalloproteinase and tissue inhibitor of metalloproteinase during
      tachycardia-induced cardiomyopathy by rapid atrial pacing in dogs.
AB  - BACKGROUND: It was the aim of this study to investigate the variation in
      metalloproteinase and tissue inhibitor of metalloproteinase (TIMP) connexin
      levels during tachycardia-induced cardiomyopathy (TIC). METHODS: Canine models of
      TIC were established by rapid right atrial pacing at 350-400 beats per min for 8
      weeks in 11 dogs, with another 6 dogs acting as sham operation group.
      Echocardiography, left ventricular pressure and its first derivation with time
      (positive and negative maximum, dp/dt(max) and -dp/dt(max)), as well as
      intracardiac electrograms were recorded before and after rapid pacing at 1, 4 and
      8 weeks. Data were acquired in sinus rhythm. Ultrastructural changes in left
      ventricular tissue were observed by transmission electron microscope. The
      relative abundance of matrix metalloproteinase (MMP)-9 and TIMP-1 was studied by
      immunoblotting. RESULTS: The following hemodynamic changes were detected after 8
      weeks of rapid pacing: the TIC group had decreased dp/dt(max) (p < 0.05), the
      left ventricular relaxation time constant (tau) was prolonged (p < 0.05), both
      left ventricular end-diastolic volume and left ventricular end-systolic volume
      were decreased (p <0.05), left ventricular end-diastolic pressure was
      significantly increased (p <0.05), and -dp/dt(max) was significantly decreased (p
      <0.001) compared with the control group; no statistical differences in the left
      ventricular ejection fraction between weeks 1, 4 or 8 (p >0.05) were observed,
      but left ventricular ejection fraction was significantly decreased after 1 week
      of pacing (p < 0.05). The left ventricular end-diastolic volume was increased
      after 1 week of pacing compared with the control group (24.15 +/- 8.15 vs.11.19
      +/- 4.41 ml; p <0.05), as shown by echocardiography. Compared with the control
      group, MMP-9 was significantly higher (0.217 +/- 2.16 E-02 vs. 0.314 +/- 5.263 E
      02; p < 0.001), while TIMP-1 was decreased (0.230 +/- 8.944 E-02 vs. 0.120 +/-
      9.258 E-03; p < 0.001). CONCLUSIONS: Ventricular dilatation and systolic
      dysfunction occurred after 1 week of rapid right atrial pacing. Enlarged and
      disarrayed fibers and mitochondria with disintegrated crystal and an anarchic
      pattern were observed. Additionally, moderate dilation of the rough endoplasmic
      reticulum and intercalated disk discontinuity were seen after 8 weeks of pacing,
      and MMP-9 was increased and TIMP-1 was decreased after the same time period.

PMID- 16612066
TI  - Clinical features and outcome of patients with apical hypertrophic cardiomyopathy
      in Taiwan.
AB  - OBJECTIVES: The aim of this study was to analyze clinical characteristics and the
      outcome of patients with apical hypertrophic cardiomyopathy (ApHCM) followed in a
      Taiwan tertiary referral medical center. BACKGROUND: ApHCM is regarded as a
      subgroup of nonobstructive HCM that occurs largely in Japanese patients. The
      clinical features, gender differences and prognosis of the disease in Taiwan are
      poorly understood. METHODS: A retrospective cohort study with 40 patients was
      performed. Diagnosis was based on the demonstration of left ventricular
      hypertrophy by echocardiography. Clinical features, cardiovascular morbidity and
      mortality were analyzed. Multiple logistic regression was used to adjust for
      potential confounding factors. RESULTS: Among 40 patients, males predominated
      with a percentage of 75%. The female patients obviously had later onset of
      presentation (mean age +/- SD, 62.2 +/- 5.7 vs. 54.1 +/- 11.4 years; p = 0.038).
      During a mean follow-up of 72.2 +/- 60.1 months, there was no mortality. However,
      13 patients (32.5%) had one or more major cardiovascular morbidities, the most
      frequent being syncope or near syncope (15%) and ischemic stroke-associated
      atrial fibrillation (10%). In a multivariate analysis, left atrial enlargement
      (odds ratio 5.85, 95% CI 1.15-29.40; p = 0.034) was the only predictor of
      cardiovascular morbidity. CONCLUSIONS: Patients with ApHCM in Taiwan have a
      benign clinical course without association with sudden death and cardiovascular
      mortality. Left atrial enlargement was the only identified predictor of
      cardiovascular morbidity

PMID- 16612067
TI  - Differential densities of muscarinic acetylcholine receptor and I(K,ACh) in
      canine supraventricular tissues and the effect of amiodarone on cholinergic
      atrial fibrillation and I(K,ACh).
AB  - BACKGROUND: Vagal nerve plays an important role in the induction and maintenance
      of atrial fibrillation (AF). This study investigated the differential densities
      of M2 receptor and acetylcholine-induced inward rectifier K+ current (I(K,ACh))
      in atrial appendage, atrium, pulmonary vein (PV) and super vena cava (SVC) to
      discuss the role of atrial appendage and PV in cholinergic AF. METHODS AND
      RESULTS: In 10 dogs, action potential duration was determined at 24 sites during
      bilateral cervical vagal stimulation and amiodarone administration. AF could be
      induced at first in right atrial appendage (RAA) and right atrium (RA) without
      left atrial appendage (LAA) and left atrium (LA). Amiodarone decreased the
      initiation of AF in vivo. Western blot and patch clamp were used to determine M2
      receptor and I(K,ACh) in RAA, LAA, RA, LA, PV and SVC. The densities of M2
      receptor and I(K,ACh) in LAA, RAA and LA were higher than that in RA, PV and SVC
      (21.34 +/- 0.92 vs. 8.24 +/- 0.45 pA/pF, p < 0.05). Furthermore, the densities of
      the M2 receptor and I(K,ACh) in LAA and RAA were higher than that in LA (21.34 +/
      0.92 vs. 14.17 +/- 0.65 pA/pF, p < 0.05). After amiodarone administration,
      densities of I(K,ACh) in LA and RA were not different, but densities of I(K,ACh
      )were also less in atrium than in atrial appendage. CONCLUSIONS: Densities of the
      M2 receptor and I(K,ACh) are higher in atrial appendage than other sites. Atrial
      appendage perhaps plays an important role in initiation of cholinergic AF.
      However, PV and SVC less often play an important role in vagotonic paroxysmal AF.
      Reduced dispersion of I(K,ACh) is the mechanism for amiodarone to therapy AF.

PMID- 16612068
TI  - Effect of hormone replacement therapy on plasma lipoproteins and apolipoproteins,
      endothelial function and myocardial perfusion in postmenopausal women with
      estrogen receptor-alpha IVS1-397 C/C genotype and established coronary artery
      disease.
AB  - Effect of hormone replacement (HRT) therapy on plasma lipoproteins and
      apolipoproteins, endothelial function and myocardial perfusion in postmenopausal
      women with estrogen receptor-alpha (ER-alpha) IVS1-397 C/C genotype and
      established coronary artery disease. BACKGROUND/AIMS: Associations between
      various ER-alpha polymorphisms and clinical phenotypes have been studied,
      including lipid levels and coronary atherosclerosis. We studied 48 postmenopausal
      women to determine the effect of ER-alpha IVS1-397 polymorphism on the response
      to treatment with HRT. METHODS: The study had a randomized, double-blind, placebo
      controlled and crossover design. Patients were divided into two groups according
      to ER-alpha IVS1-397 polymorphism: CC genotype (n = 9); CT or TT genotype (n =
      39). HRT was given continuously for 4 weeks, with 4-week washout periods between
      the treatment periods. Brachial artery Doppler and Tl-201 scintigraphy were
      performed at the end of each treatment period. RESULTS: HRT lowered total
      cholesterol, LDL-c and Apo-B levels from baseline values (all p < 0.05) and to a
      similar degree in CC and CT/TT genotype patients. HRT increased estradiol, HDL-c
      and Apo A-1 levels relative to baseline values, but to a greater degree in CC
      patients (p = 0.04, 0.05 and 0.04 by ANOVA, respectively). HRT increased peak
      forearm blood flow, brachial artery diameter during reactive hyperemia and
      endothelium-dependent dilation in both groups, but to a greater degree in CC
      patients (p = 0.03, 0.03 and 0.04 by ANOVA, respectively). Summed stress and rest
      scores were also more markedly reduced in CC patients (p = 0.04 and 0.05,
      respectively). The increase in estradiol levels was strongly correlated with the
      improvement in endothelium-dependent dilation (r = 0.66, p < 0.01), which in turn
      showed negative correlation with summed stress (r = -0.62, p < 0.01) and rest
      scores (r = -0.52, p < 0.05) in the CC genotype group. CONCLUSION: These data
      suggest that the improvement in endothelium-dependent dilation and the reduction
      in perfusion abnormalities by increasing estradiol levels with HRT in
      postmenopausal women with coronary artery disease may differ with respect to
      different genotypes, the effect being more prominent in those patients with ER
      alpha IVS1-397 CC genotype.

PMID- 16612069
TI  - Coronary artery bypass grafting is associated with a significant worsening of QT
      dynamicity and heart rate variability.
AB  - BACKGROUND: Imbalance in autonomic nervous system and impaired myocardial
      repolarization has been shown to increase the risk for arrhythmias in patients
      with coronary artery disease. This study evaluated the effects of coronary artery
      bypass grafting (CABG) on heart rate variability and QT interval dynamicity in
      subjects with coronary artery disease undergoing elective CABG surgery. METHODS:
      The study group consisted of 68 consecutive patients (mean age +/-SD: 61 +/- 9
      years) with coronary artery disease who underwent elective CABG. Twenty-four-hour
      Holter monitoring was performed 2-5 days before cardiac surgery and was repeated
      10 days after CABG. ELATEC holter software was used to calculate heart rate
      variability and QT dynamicity parameters. All subjects had a complete history,
      laboratory examination and transthoracic echocardiography. RESULTS: All patients
      had beta-blocking agent medication pre- and postoperatively. Standard deviation
      of all NN intervals for a selected time period, square root of the mean of the
      sum of the squares of differences between adjacent RR intervals, the proportion
      of differences in successive NN intervals greater than 50 ms, normalized low
      frequency power, and normalized high-frequency power were significantly decreased
      after CABG surgery, whereas low-frequency/high-frequency ratio was significantly
      increased after CABG. QT/RR slopes over 24 h were significantly increased after
      CABG surgery for QT end and QT apex (QTapex/RR: 0.16 +/- 0.13 vs. 0.28 +/- 0.19,
      p < 0.001; QTend/RR: 0.18 +/- 0.13 vs. 0.36 +/- 0.23, p < 0.001). CONCLUSION:
      This prospective study showed for the first time that CABG was associated with a
      significant worsening of heart rate variability and QT dynamicity parameters in
      the postoperative period.

PMID- 16612070
TI  - Dilated cardiomyopathy: an unusual presentation of aortic coarctation in an
      infant.
AB  - Coarctation of the aorta commonly presents in infancy as congestive heart
      failure, or later in childhood as hypertension or as a heart murmur. However, we
      experienced a unique infant case of isolated coarctation presenting with acute
      decompensation of a dilated cardiomyopathy, which recovered completely 8 months
      postoperatively. Our report highlights the previously unreported presentation of
      coarctation in infancy as a dilated cardiomyopathy. It also implies that before
      we label any patient presenting with a dilated cardiomyopathy as an idiopathic
      cardiomyopathy, we must exclude all possible specific causes of myocardial
      dysfunction because many such specific cardiomyopathies are curable and very
      rewarding, just like our patient.

PMID- 16612071
TI  - Urgent cardiac resynchronization therapy in patients with decompensated chronic
      heart failure receiving inotropic therapy. A case series.
AB  - BACKGROUND: It remains unknown whether patients with severe decompensated class
      IV heart failure (HF) receiving intravenous inotropic treatment benefit from
      cardiac resynchronization therapy (CRT). METHODS: We identified patients who
      underwent urgent CRT implantation due to decompensated class IV HF necessitating
      intravenous inotropic therapy. RESULTS: Of 10 patients with chronic ischemic
      cardiomyopathy (median QRS duration of 170 ms), CRT implantation was associated
      with symptomatic improvement in 8 patients. The mortality rate was 50% during a
      median follow-up of 9.5 months, with a median CRT-to-death duration of 6 months.
      CONCLUSIONS: CRT was feasible among class IV patients receiving inotropic
      treatment and was associated with clinical improvement.

PMID- 16612072
TI  - Congenital left ventricular aneurysms and diverticula: definition,
      pathophysiology, clinical relevance and treatment.
AB  - A congenital left ventricular aneurysm or diverticulum is a rare cardiac
      malformation; 411 cases have been reported since its first description in 1816,
      and other cardiac, vascular or thoraco-abdominal abnormalities have been shown in
      about 70%. It appears to be a developmental anomaly, starting in the 4th
      embryonic week. Diagnosis can be made after exclusion of coronary artery disease,
      local or systemic inflammation or traumatic causes as well as cardiomyopathies.
      Clinically, most congenital left ventricular aneurysms and diverticula are
      asymptomatic or may cause systemic embolization, heart failure, valvular
      regurgitation, ventricular wall rupture, ventricular tachycardia or sudden
      cardiac death. Diagnosis is established by imaging studies such as
      echocardiography, magnetic resonance imaging or left ventricular angiography,
      visualizing the structural changes and accompanying abnormalities. Mode of
      treatment has to be individually tailored and depends on clinical presentation,
      accompanying abnormalities and possible complications; treatment options include
      surgical resection especially in symptomatic patients, anticoagulation after
      systemic embolization, radiofrequency ablation or implantation of an implantable
      cardioverter defibrillator in case of symptomatic ventricular tachycardia,
      occasionally combined with class I or III antiarrhythmic drugs.

PMID- 16612073
TI  - Aneurysms of the sinuses of Valsalva.
AB  - Sinus of Valsalva aneurysms are rare cardiac anomalies which may be acquired or
      congenital, most commonly involving the right or noncoronary sinuses. The
      congenital aneurysms are more common and often caused by weakness at the junction
      of the aortic media and the annulus fibrosus. Acquired aneurysms are caused by
      conditions affecting the aortic wall, such as infections (syphilis, bacterial
      endocarditis, or tuberculosis), trauma, or connective tissue disorders.
      Unruptured aneurysms are usually found incidentally during diagnostic studies.
      More commonly, sinus of Valsalvaaneurysms are diagnosed after clinical sequelae
      of rupture. Diagnosis of sinus of Valsalva aneurysm is facilitated by
      echocardiography, contrast aortography, and more recently, magnetic resonance
      imaging. Repair is generally required for ruptured aneurysms; unruptured
      aneurysms encroaching on nearby structures, causing myocardial ischemia, or
      having the potential to rupture warrant repair. A review of the literature is
      presented focusing on anatomy, clinical presentation of ruptured and unruptured
      aneurysms, noninvasive diagnostic modalities, and techniques for repair of this
      anomaly.

PMID- 16612074
TI  - Effects of fluid shear stress on eNOS mRNA expression and NO production in human
      endothelial progenitor cells.
AB  - The increases in physiological levels of fluid shear stress have beneficial
      effects on vascular homeostasis. Endothelial progenitor cells (EPCs) play an
      important role in the maintenance of endothelial integrity. We hypothesized that
      shear stress-mediated vascular protection is related to the upregulation of
      endothelial nitric oxide synthase expression in EPCs. The human EPCs exposed to
      in vitro shear stress levels of 5, 15 and 25 dyn/cm(2) for 4 h. In vitro shear
      stress, in a dose-dependent fashion, increased the endothelial nitric oxide
      synthase mRNA expression and the nitric oxide production in human EPCs. The
      present findings for the first time provide novel insights into the mechanisms of
      the physiological levels of fluid shear stress on the regulation of human EPC
      biologic phenotype as a potential factor, which might contribute to vascular
      protective activities in humans although evidence is indirect.

PMID- 16612075
TI  - QT interval dispersion as a new marker of restenosis after percutaneous
      transluminal coronary angioplasty of isolated single-vessel coronary artery
      stenosis.
AB  - BACKGROUND: There are no reliable non-invasive markers of restenosis after
      percutaneous transluminal coronary angioplasty (PTCA). The aim of our study was
      to measure changes in QT interval dispersion after PTCA and to determine whether
      restenosis subsequently affects QT interval dispersion. METHODS AND RESULTS:
      Fifty-six consecutive patients - 41 men and 15 women (mean age: 56.2 +/-8.3
      years) - with isolated stenosis of the left anterior descending artery who
      underwent successful PTCA were studied. A symptom-limited treadmill exercise test
      was performed within 7 days after PTCA and then again before repeated
      angiography. Repeated coronary angiography revealed restenosis in 15 patients
      (26.8%) and no signs of significant stenosis in 41 patients (73.2%). QT interval
      dispersion in the group of patients with restenosis measured before exercise
      increased from baseline 34 +/- 7 to 49 +/- 15 ms after 6 months (p < 0.01) and QT
      interval dispersion measured immediately after exercise increased from baseline
      38 +/- 4 to 68 +/- 21 ms after 6 months (p < 0.001). In contrast, patients
      without restenosis showed no significant changes in QT interval dispersion
      measured before (baseline: 34 +/- 9 ms; after 6 months 33 +/- 12 ms; p = NS) and
      immediately after exercise (baseline: 34 +/- 12 ms; after 6 months: 33 +/- 10; p
      = NS). When QT interval dispersion > or =60 ms (measured 6 months after PTCA
      procedure) was considered as a potential marker of restenosis, this indicator had
      very high sensitivity and specificity when measured immediately after exercise
      (80 and 95% respectively). CONCLUSIONS: QT interval dispersion significantly
      increases in the group of patients with documented restenosis and may be a
      simple, non-invasive marker of restenosis. However, further studies are needed to
      confirm this observation.

PMID- 16612076
TI  - Spondyloarthropathy-associated aortitis and massive thickening of the aortic
      mitral curtain: diagnosis by echocardiography.
AB  - Cardiac involvement in reactive arthritis is well-recognized, and usually results
      in aortic regurgitation, proximal aortitis, and conduction system abnormalities.
      Aortitis is usually recognized in conjunction with aortic regurgitation, but can
      be diagnosed in isolation as aortic root thickening and subaortic fibrous
      ridging. We report a case of spondyloarthropathy-associated aortitis diagnosed by
      transesophageal echocardiography. The case illustrates the aortic root pathology
      and highlights the unique morphologic echocardiographic feature of this
      condition, prominent thickening of the aortic-mitral curtain.

PMID- 16612077
TI  - Extra-cellular matrix in the craniofacial complex. Proceedings of a symposium at
      the American Association of Dental Research. March 10, 2005.

PMID- 16612078
TI  - The extracellular matrix environment in suture morphogenesis and growth.
AB  - Sutures are the major bone growth sites of the craniofacial skeleton and form in
      response to developmental approximation of and interaction between two opposing
      osteogenic fronts. Premature obliteration of these craniofacial bone growth sites
      or craniosynostosis results in compensatory growth at other bone growth sites,
      with concomitant craniofacial dysmorphology. While much is now known about the
      growth and transcriptional factor regulation of suture formation and maintenance,
      little about the nature of the extracellular environment within sutures and their
      surrounding bones has been described. This review elucidates the nature of the
      sutural extracellular matrix and its role in mediating suture maintenance and
      growth through the regulation of cellular and biomechanical signaling.

PMID- 16612079
TI  - Mice deficient in biglycan and fibromodulin as a model for temporomandibular
      joint osteoarthritis.
AB  - The temporomandibular joint (TMJ) within the craniofacial complex is unique. In
      humans, the TMJ can become diseased resulting in severe and disabling pain. There
      are no cures for TMJ disease at this time. Animal models of TMJ disease are
      scarce, but some exist, and they are described in this paper. We present in
      greater detail one animal model that is deficient in two extracellular matrix
      (ECM) proteoglycans, biglycan (BGN) and fibromodulin (FMOD). Doubly deficient
      BGN/FMOD mice develop premature TMJ osteoarthritis (OA). In order to explore the
      mechanistic basis of TMJ-OA, tissues from the condyle of mutant mice were
      examined for their relative capacity to differentiate and undergo apoptosis. Our
      data show that there is a redistribution of the critical ECM protein, type II
      collagen, in mutant mice compared with controls. Mutant mice also have increased
      apoptosis of the chondrocytes embedded in the articular cartilage. We speculate
      that the overall imbalance in apoptosis may be the cellular basis for the
      abnormal production of structural ECM proteins. The abnormal production of the
      ECM could, in turn, lead to premature erosion and degradation of the articular
      surface resulting in TMJ-OA. These data underscore the importance of the ECM in
      controlling the structural integrity of the TMJ.

PMID- 16612080
TI  - Variation in mineral properties in normal and mutant bones and teeth.
AB  - Hydroxyapatite mineral is deposited in an organized fashion in the matrices of
      bones and teeth. The amount of mineral present, the composition of the mineral,
      and the size of the mineral crystals varies with both tissue and animal age,
      diet, health status, and the tissue being examined. Here, we review methods for
      measuring these differences in mineral properties and provide some illustrations
      from bones and teeth of animals in which the small leucine-rich proteoglycans
      (biglycan and decorin) were ablated. Differences in mineral properties between
      biglycan-deficient bones and teeth are related to the functions of this small
      proteoglycan in these tissues.

PMID- 16612081
TI  - Collagenase in cranial morphogenesis.
AB  - Collagen is the most abundant extracellular matrix protein in connective tissues
      of higher animals. The growth of connective tissues is intimately linked to the
      ability to model and remodel the collagen-rich matrices of the organism at
      critical points during development and growth to allow expansion and adaptation
      of tissue interfaces. The mammalian cranium is one such place where collagen
      remodeling is required for proper growth, and this review explores the
      consequences of abrogated collagen remodeling as they materialize in a mouse
      model deficient for the membrane type 1 matrix metalloproteinase.

PMID- 16612082
TI  - Role of matrix Gla protein in parathyroid hormone inhibition of osteoblast
      mineralization.
AB  - Parathyroid hormone (PTH) exerts biphasic effects on bone, dependent on the
      frequency and dose of administration. The catabolic actions of PTH on bone have
      been associated with continuous treatment, an increase in osteoblast-mediated
      resorption of bone via osteoclast activation, and inhibition of osteoblast
      activity and mineralization. Downregulation of differentiation markers and
      inhibition of mineralization by PTH have been reported in primary calvarial
      explants and osteoblast cell lines. Using MC3T3-E1 osteoblast-like cells, we have
      shown that matrix Gla protein (MGP) can be induced by PTH, and that this
      induction may explain the PTH-mediated inhibition of osteoblast
      biomineralization. MGP is a known inhibitor of mineralization, and mice deficient
      in Mgp show severe vascular calcification and premature bone mineralization. This
      review discusses the role of MGP in mineralization, comparing bone and vascular
      mineralization. In addition to MGP, the regulation and possible role of
      osteopontin, another known regulator of osteoblast mineralization, in PTH
      mediated regulation of bone and vascular mineralization is discussed.

PMID- 16612083
TI  - Hierarchies of extracellular matrix and mineral organization in bone of the
      craniofacial complex and skeleton.
AB  - Structural hierarchies are common in biologic systems and are particularly
      evident in biomineralized structures. In the craniofacial complex and skeleton of
      vertebrates, extracellular matrix and mineral of bone are structurally ordered at
      many dimensional scales from the macro level to the nano level. Indeed, the
      nanocomposite texture of bone, with nanocrystals of apatitic mineral embedded
      within a crosslinked matrix of fibrillar and nonfibrillar proteins, imparts to
      bone the very mechanical properties and toughness it needs to function in vital
      organ protection, musculoskeletal movement and mastication. This article focuses
      on how hierarchies of extracellular matrix protein organization influence bone
      cell behavior, tissue architecture and mineralization. Additional attention is
      given to recent work on the molecular determinants of mineral induction in bone,
      and how the mineralization process is subsequently regulated by inhibitory
      proteins.

PMID- 16612084
TI  - Essential roles of ameloblastin in maintaining ameloblast differentiation and
      enamel formation.
AB  - During tooth development, dental epithelial cells interact with extracellular
      matrix components, such as the basement membrane and enamel matrix. Ameloblastin,
      an enamel matrix protein, plays a crucial role in maintaining the ameloblast
      differentiation state and is essential for enamel formation. Ameloblastin-null
      mice developed severe enamel hypoplasia. In mutant mice, dental epithelial cells
      started to differentiate into ameloblasts, but ameloblasts soon lost cell
      polarity, proliferated, and formed multiple cell layers, indicative of some
      aspects of preameloblast phenotypes. In addition, the expression of amelogenin,
      another component of the enamel matrix, was specifically reduced in mutant
      ameloblasts. More than 20% of amelobastin-null mice developed odontogenic tumors.
      We also found that recombinant ameloblastin specifically bound to ameloblasts and
      inhibited proliferation of dental epithelial cells. These results suggest that
      ameloblastin is an important regulator to maintain the differentiation state of
      ameloblasts.

PMID- 16612085
TI  - The use of animal models to explore amelogenin variants in amelogenesis
      imperfecta.
AB  - Amelogenin proteins are secreted by ameloblast cells during tooth development.
      Because of extensive alternative splicing of the amelogenin primary RNA
      transcript, and because systematic proteolysis results in many additional
      peptides during enamel maturation, it has been difficult to assign function to
      individual amelogenins. Targeted deletions and transgenic mice have been
      generated in order to better understand amelogenin protein function in vivo. From
      these murine models, we have determined that amelogenins are responsible for
      normal enamel thickness and structure, but not for initiation of enamel mineral
      formation at the dentin-enamel junction. Although it is now clear that the
      amelogenin (AmelX) gene exists in a nested orientation and that AmelX is
      expressed at a low level in various developing tissues, the significance of these
      findings is incompletely understood. Future studies are expected to answer
      remaining questions concerning structure/function relationships among these
      'enamel proteins'.

PMID- 16612086
TI  - Amelogenin supra-molecular assembly in vitro compared with the architecture of
      the forming enamel matrix.
AB  - Tooth enamel is formed in the extracellular space within an organic matrix
      enriched in amelogenin proteins. Amelogenin nanosphere assembly is a key factor
      in controlling the oriented and organized growth of enamel apatite crystals.
      Recently, we have reported the formation of higher ordered structures resulting
      from organized association and self-orientation of amelogenin nanospheres in
      vitro. This remarkable hierarchical organization includes self-assembly of
      amelogenin molecules into subunits of 4-6 nm in diameter followed by their
      assembly to form nanospheres of 15-25 nm in radii. Chains of >100 nm length are
      then formed as the result of nanosphere association. These linear arrays of
      nanospheres assemble to form the microribbons that are hundreds of microns in
      length, tens of microns in width, and a few microns in thickness. Here, we review
      the step by step process of amelogenin self-assembly during the formation of
      microribbon structures in vitro. Assembly properties of selected amelogenins
      lacking the hydrophilic C terminus will then be reviewed. We will consider
      amelogenin as a template for the organized growth of crystals in vitro. Finally,
      we will compare the structures formed in vitro with globular and periodic
      structures observed earlier, in vivo, by different sample preparation conditions.
      We propose that the alignment of amelogenin nanospheres into long chains is
      evident in vivo, and is an important indication for the function of this protein
      in controlling the oriented and elongated growth of apatite crystals during
      enamel biomineralization.

PMID- 16612087
TI  - Proteomics and genetics of dental enamel.
AB  - The initiation of enamel crystals at the dentino-enamel junction is associated
      with the expression of dentin sialophosphoprotein (DSPP, a gene normally linked
      with dentin formation), three 'structural' enamel proteins--amelogenin (AMELX),
      enamelin (ENAM), and ameloblastin (AMBN)--and a matrix metalloproteinase,
      enamelysin (MMP20). Enamel formation proceeds with the steady elongation of the
      enamel crystals at a mineralization front just beneath the ameloblast distal
      membrane, where these proteins are secreted. As the crystal ribbons lengthen,
      enamelysin processes the secreted proteins. Some of the cleavage products
      accumulate in the matrix, others are reabsorbed back into the ameloblast. Once
      crystal elongation is complete and the enamel layer reaches its final thickness,
      kallikrein 4 (KLK4) facilitates the breakdown and reabsorption of accumulated
      enamel matrix proteins. The importance of the extracellular matrix proteins to
      proper tooth development is best illustrated by the dramatic dental phenotypes
      observed in the targeted knockouts of enamel matrix genes in mice (Dspp, Amelx,
      Ambn, Mmp20) and in human kindreds with defined mutations in the genes (DSPP,
      AMELX, ENAM, MMP20, KLK4) encoding these matrix proteins. However, ablation
      studies alone cannot give specific mechanistic information on how enamel matrix
      proteins combine to catalyze the formation of enamel crystals. The best approach
      for determining the molecular mechanism of dental enamel formation is to
      reconstitute the matrix and synthesize enamel crystals in vitro. Here, we report
      refinements to the procedures used to isolate porcine enamel and dentin proteins,
      recent advances in the characterization of enamel matrix protein
      posttranslational modifications, and summarize the results of human genetic
      studies that associate specific mutations in the genes encoding matrix proteins
      with a range of dental phenotypes.

PMID- 16612088
TI  - Role of phosphophoryn in dentin mineralization.
AB  - Mineral deposition is essential for the development of hard tissues like bone and
      teeth. In matrix-mediated mechanisms responsible for dentin formation, type I
      collagen defines the framework for mineral deposition and by itself is not
      sufficient to support nucleation of hydroxyapatite. However, in the presence of
      non-collagenous proteins, nucleation sites have been identified within the hole
      regions of the fibrils, and at these sites, mineral crystals can grow and
      propagate. Non-collagenous proteins constitute 5-10% of the total extracellular
      matrix proteins. They are embedded within the mineral deposits, suggesting a
      possible interaction with the mineral phase. During dentin formation,
      phosphophoryn (PP), an abundant macromolecule in the extracellular matrix, can
      initiate mineral deposition in localized regions by matrix-mediated
      mineralization mechanism. In our work, we have demonstrated that PP, due to its
      highly phosphorylated post-translational modification, can bind calcium ions with
      high affinity and at the same time aggregate collagen fibrils at the
      mineralization front. Molecular modeling has further demonstrated that the
      spacing of the carboxyl and phosphate groups present on PP might be essential for
      dictating the crystal orientation relative to the collagen substrate. Thus, PP
      may provide the interface linkage between mineral crystal and collagen fibrils.

PMID- 16612089
TI  - Differential regulation of dentin matrix protein 1 expression during
      odontogenesis.
AB  - Dentin matrix protein 1 (DMP1) is highly expressed in mineralized tooth and bone.
      Both in vitro and in vivo data show that DMP1 is critical for mineralization and
      tooth morphogenesis (growth and development). In this study, we studied Dmp1 gene
      regulation. The in vitro transient transfection assay identified two important
      DNA fragments, the 2.4- and 9.6-kb promoter regions. We next generated and
      analyzed transgenic mice bearing the beta-galactosidase (lacZ) reporter gene
      driven by the 2.4- or 9.6-kb promoter with the complete 4-kb intron 1. The 9.6-kb
      Dmp1-lacZ mice conferred a DMP1 expression pattern in odontoblasts identical to
      that in the endogenous Dmp1 gene. This is reflected by lacZ expression in Dmp1
      lacZ knock-in mice during all stages of odontogenesis. In contrast, the 2.4-kb
      Dmp1-lacZ mice display activity in odontoblast cells only at the early stage of
      odontogenesis. Thus, we propose that different transcription factors regulate
      early or later cis-regulatory domains of the Dmp1 promoter, which gives rise to
      the unique spatial and temporal expression pattern of Dmp1 gene at different
      stages of tooth development.

PMID- 16612090
TI  - Defining the roots of cementum formation.
AB  - Significant progress has been seen in research aimed at regeneration of the
      disease-damaged periodontium. Our own strategy has been to approach periodontal
      tissue development (i.e. root, cementum, periodontal ligament, and bone) as a
      source for the identification of key regulators of cellular processes that may be
      applicable to periodontal tissue repair. Specifically, enamel-like molecules,
      bone morphogenetic proteins (BMPs), and phosphates have been investigated for
      their role in altering gene expression and cell functions in follicle cells,
      periodontal ligament cells, and cementoblasts. Amelogenin, leucine-rich
      amelogenin peptide, and tyrosine-rich amelogenin peptide have been found to
      similarly affect cementoblast gene expression and cementoblast-mediated
      mineralization in vitro; however, these enamel-like factors do not increase cell
      proliferation as has been observed in cells treated with Emdogain (Biora AB,
      Malmo, Sweden), an enamel matrix derivative. BMP-2 has been found to promote
      differentiation of follicle cells into a cementoblast/osteoblast phenotype, and
      BMP-3 is being investigated as a negative regulator of mineralization. The
      increased ratio of phosphate to pyrophosphate in the local region during root
      development has been found to significantly enhance the extent of cementum
      formation in animal models. Furthermore, phosphate has been identified as a
      regulator of cementoblast SIBLING (small integrin-binding ligand N-linked
      glycoprotein) gene expression in vitro. These investigations of candidate factors
      for periodontal regeneration have uncovered mechanisms regulating gene expression
      and cell function in cells controlling the behavior of periodontal tissues (i.e.
      follicle cells, periodontal cells, and cementoblasts) and offer new directions to
      consider for clinical repair of periodontal defects.

PMID- 16612091
TI  - Therapy with budesonide in patients with refractory sprue.
AB  - INTRODUCTION: Refractory sprue (RS) is a rare malabsorption syndrome, which often
      requires long-term corticosteroid treatment. Locally acting budesonide could
      replace systemic corticosteroid therapy and reduce toxicity in patients with RS.
      AIMS: To evaluate the efficacy and toxicity of budesonide in patients with RS.
      PATIENTS AND METHODS: Clinical and histological data from patients with RS who
      received budesonide were analyzed. RS was defined as villous atrophy and
      malabsorption in spite of a strict gluten-free diet persisting for >6 months or
      requiring earlier therapeutic intervention. RESULTS: We identified 9 patients (1
      with autoimmune enteropathy, 4 with RS type I without and 3 with RS type II with
      signs of early T cell lymphoma and 1 with CD4-positive sprue-like intestinal T
      cell lymphoma), who received 9 mg/day of budesonide (range 6-12) for 24 months (1
      60), and 7 of whom had an initial treatment with 40 mg/day of prednisolone (30
      60) for 4 months (1-144). The initial body mass index was 18 (13.1-22.8) and
      increased similarly under prednisolone [21.5 (14.9-26.7), p < 0.05] and
      budesonide therapy [21 (18-27.2), p < 0.05]. The stool frequency per day also
      decreased similarly from 6 (2-8) to 2 (1-3) and 2 (1-5), each p < 0.05, under
      prednisolone and budesonide therapy, respectively. Two patients with RS type II
      did not respond and 7, including all 4 with RS type I, were clinically stable
      with budesonide therapy. Skin fragility in 1 patient was the only adverse effect
      of budesonide therapy. CONCLUSIONS: Budesonide may be an effective treatment
      option in patients with RS type I, which can stabilize the clinical condition
      similar to prednisolone.

PMID- 16612092
TI  - Screening for the formation of reactive oxygen species and of NO in muscle tissue
      and remote organs upon mechanical trauma to the mouse hind limb.
AB  - BACKGROUND: Until now, no systematic surveys exist in the literature on the early
      local and systemic generation of reactive oxygen species and of nitric oxide in
      response to muscle crush injury. Therefore, this study aims to evaluate the
      formation of reactive oxygen species and nitric oxide in different tissues
      (injured and contralateral muscle, liver, kidney, spleen and blood) that is
      induced by closed muscle trauma. METHODS: 5, 45 and 180 min after induction of
      blunt trauma to the mouse gastrocnemius muscle, animals were sacrificed, tissues
      harvested and homogenized, and analyzed for their content of glutathione, nitrate
      and thiobarbituric acid-reactive substances. RESULTS: The local formation of
      reactive oxygen species in the injured muscle started immediately upon induction
      of the mechanical trauma as indicated by changes in the glutathione redox
      balance. Liver and kidney did not show any response to trauma; however, a marked
      and immediate increase in the splenic nitrate content was detected, thus
      suggesting a specific nitric oxide-dependent response of splenic cells to injury.
      CONCLUSION: We conclude that immediately after the induction of trauma a
      formation of reactive oxygen species takes place at the site of crush injury.
      This might constitute the basis of further damage to the injured tissue by free
      radical-dependent mechanisms. The immediate formation of nitric oxide within the
      spleen upon muscle crush appears to represent a specific signalling mechanism of
      the body in response to distant organ injury.

PMID- 16612093
TI  - RF-assisted cystectomy and pericystectomy: a new technique in the treatment of
      liver hydatid disease.
AB  - BACKGROUND: Radiofrequency (RF) energy has been used for ablation and resection
      of liver tumors. PURPOSE: To present a new technique for the treatment of liver
      hydatid cyst disease. MATERIAL AND METHODS: Two patients with liver hydatid
      disease treated with RF energy cauterization and surgical resection are
      presented. Cystectomy was performed in a female patient aged 35 years and
      pericystectomy was carried out in another female patient aged 55 years using RF
      energy cauterization. Blood was not needed during the operation. RITA System
      (RITA Model 1500 RF Generator, RITA Medical Systems, Inc., USA) was used during
      the procedure. CONCLUSION: Cystectomy and pericystectomy in liver hydatid disease
      can be successfully performed with the assistance of RF energy.

PMID- 16612094
TI  - Arboreal locomotion in wild black-and-white snub-nosed monkeys (Rhinopithecus
      bieti).
AB  - This paper presents spatiotemporal gait parameters of arboreal locomotion in the
      colobine Rhinopithecus bieti in its natural habitat. While adult females used
      exclusively either extended-elbow vertical climbing or pulse climbing, the much
      larger adult males preferred the less demanding flexed-elbow vertical climbing on
      thin trees or on trunks with handholds. If sex-specific differences are taken
      into consideration, the differences between flexed-elbow and extended-elbow
      vertical climbing in Rhinopithecus parallel those observed in Ateles. During
      flexed-elbow vertical climbing, the gait parameters of R. bieti are very similar
      to those of spider monkeys (Ateles fusciceps) or bonobos (Pan paniscus). Maximum
      limb joint excursions also lie in the range of hominoids and atelines and are
      clearly larger than in Macaca fuscata. It seems likely that climbing kinematics
      may differ more between Rhinopithecus and macaques than between Rhinopithecus and
      hominoids or atelines.

PMID- 16612095
TI  - Evidence of leopard predation on bonobos (Pan paniscus).
AB  - Current models of social organization assume that predation is one of the major
      forces that promotes group living in diurnal primates. As large body size renders
      some protection against predators, gregariousness of great apes and other large
      primate species is usually related to other parameters. The low frequency of
      observed cases of nonhuman predation on great apes seems to support this
      assumption. However, recent efforts to study potential predator species have
      increasingly accumulated direct and indirect evidence of predation by leopards
      (Panthera pardus) on chimpanzees and gorillas. The following report provides the
      first evidence of predation by a leopard on bonobos (Pan paniscus).

PMID- 16612096
TI  - Feeding patterns in a small-bodied nocturnal folivore (Avahi laniger) and the
      influence of leaf chemistry: a preliminary study.
AB  - We present data on feeding patterns in Avahi laniger and compare these data to
      temporal variations in leaf chemistry. Because A. laniger is one of the smallest
      folivorous primates and has a monogastric stomach, we hypothesized that this
      lemur would display behavioural adaptations to a leaf-based diet by scheduling
      feeding times when leaves were of highest quality. Data were collected from May
      to August 2004 at the Vatoharanana site in Ranomafana National Park, Madagascar.
      A. laniger fed during different time periods despite leaf carbohydrate and
      protein concentrations exhibiting little variation throughout the night. Although
      tannin concentrations exhibited temporal fluctuations, they did not covary with
      A. laniger feeding times. We suggest that A. laniger feeding times cannot be
      explained entirely by variations in leaf chemistry.

PMID- 16612097
TI  - The locomotor behavior of Callicebus brunneus and Callicebus torquatus.
AB  - This study presents data on the positional behavior of Callicebus torquatus and
      Callicebus brunneus collected from two different localities in Peru. C. brunneus
      primarily utilizes short-distance, bounding leaps, while C. torquatus relies
      predominantly on quadrupedal walking. Both species utilize small, horizontal and
      terminal branches more than any other substrate class. We relate the differences
      in locomotor behaviors between the two species to their utilization of different
      forest levels. C. brunneus tends to reside in the understory and brush layer
      forest levels. These more discontinuous strata necessitate higher frequencies of
      short-distance leaping. C. torquatus occupies the more continuous, interconnected
      canopy level, and much of its food is found in this level. Comparisons with other
      species show that Callicebus spp. locomote along smaller-sized, horizontal
      branches using quadrupedal progression and leaping.

PMID- 16612098
TI  - A universal microsatellite multiplex kit for genetic analysis of great apes.
AB  - DNA profiling with microsatellite markers is a commonly used genetic method of
      studying the great apes. An efficient method of generating the genetic data is
      amplification of multiple microsatellites in a single PCR reaction. Here we
      describe a PCR multiplex in which 9 genetic markers can be amplified
      simultaneously, thereby saving time, expenses and DNA. This marker system can
      discriminate between all the great ape species except bonobos and chimpanzees.
      Furthermore, the cumulative probability of identity values were low for all 4
      species tested.

PMID- 16612099
TI  - A dynamic force analysis system for climbing of large primates.
AB  - Registering substrate reaction forces from primates during climbing requires the
      design and construction of customized recording devices. The technical
      difficulties in constructing a reliable apparatus hinder research on the kinetics
      of primate locomotion. This is unfortunate since arboreal locomotion, especially
      vertical climbing, is an important component of the hominoid locomotor
      repertoire. In this technical paper, we describe a custom-built climbing pole
      that allows recordings of dynamic 3-dimensional forces during locomotion on
      horizontal and sloping substrates and during vertical climbing. The pole contains
      an instrumented section that can readily be modified and enables us to register
      forces of a single limb or multiple limbs in a broad range of primates. For
      verification, we constructed a similar set-up (which would not be usable for
      primates) using a conventional force plate. Data for a human subject walking on
      both set-ups were compared. The experimental set-up records accurate and reliable
      substrate reaction forces in three orthogonal directions. Because of its
      adjustability, this type of modular set-up can be used for a great variety of
      primate studies. When combining such kinetic measurements together with kinematic
      information, data of great biomechanical value can be generated. These data will
      hopefully allow biological anthropologists to answer current questions about
      primate behaviours on vertical substrates.

PMID- 16612100
TI  - Measurement of tension-free vaginal tape trocar insertion and exit forces.
AB  - BACKGROUND/AIMS: This study aims to establish a model to measure the forces
      required for tension-free vaginal tape (TVT) trocar application using a pressure
      transducer. METHODS: A 3.5 x 3.5 cm pressure transducer was constructed from
      piezo-resistive material. The transducer digitally recorded the surface contact
      pressure (pressure = force/area) profile continuously during TVT trocar
      application. Recordings were successfully obtained from 24 subjects. RESULTS: The
      mean (standard error) peak contact pressures during application at the right and
      left side vaginal walls, and right and left side abdominal walls were 1.05 (0.12)
      pounds per square inch (psi), 1.08 (0.21) psi, 2.49 (0.3) psi and 2.49 (0.3) psi,
      respectively. On both the right and left side, pair-wise comparisons between
      trocar insertion and exit forces were significantly different (p < 0.001).
      CONCLUSION: A model has been developed by which TVT trocar application forces can
      be objectively measured. The TVT trocar exit force is substantially greater than
      the insertion force, regardless of side.

PMID- 16612101
TI  - Health status function after treatment with thermal balloon endometrial ablation
      and levonorgestrel intrauterine system for idiopathic menorrhagia: a randomized
      study.
AB  - AIM: To compare patients' health status function after treatment with thermal
      balloon endometrial ablation (TBEA) and levonorgestrel intrauterine system (LNG
      IUS) for idiopathic menorrhagia. METHODS: Forty-four patients were recruited into
      a randomized trial comparing their health status after treatment with TBEA or LNG
      IUS for idiopathic menorrhagia. RESULTS: At 1 year follow-up, the mean
      haemoglobin was significantly higher in women treated with TBEA (12.6 g/dl vs.
      10.3 g/dl, p = 0.018). Iron deficiency occurred in 13.3% from the TBEA arm and in
      50% from the LNG-IUS arm (p = 0.026). The women's mean Short Form 36
      Questionnaire general health perception scores (54.9 vs. 40.5, p = 0.024) and
      mental health scores (49.5 vs. 38.3, p = 0.021) in TBEA arm were significantly
      higher than in the LNG-IUS arm. The mental health domain score was also
      significantly lower in the LNG-IUS arm (46.1 vs. 38.3, p = 0.041). CONCLUSION:
      TBEA appears to offer better health status function at 1 year follow-up and to be
      more acceptable to our Chinese population in the treatment of idiopathic
      menorrhagia following failed medical treatment.

PMID- 16612102
TI  - Prediction of empirical p values from asymptotic p values for conditional
      logistic affected relative pair linkage analysis.
AB  - OBJECTIVE: p Values are inaccurate for model-free linkage analysis using the
      conditional logistic model if we assume that the LOD score is asymptotically
      distributed as a simple mixture of chi-square distributions. When analyzing
      affected relative pairs alone, permuting the allele sharing of relative pairs
      does not lead to a useful permutation distribution. As an alternative, we have
      developed regression prediction models that provide more accurate p values.
      METHODS: Let E(alpha) be the empirical p value, which is the proportion of
      statistical tests whose LOD score under the null hypothesis exceeds a threshold
      determined by alpha, the nominal single test significance value. We used
      simulated data to obtain values of E(alpha) and compared them with alpha. We also
      developed a regression model, based on sample size, number of covariates in the
      model, alpha and marker density, to derive predicted p values for both single
      point and multipoint analyses. To evaluate our predictions we used another set of
      simulated data, comparing the Ealpha for these data with those obtained by using
      the prediction model, referred to as predicted p values (P(alpha)). RESULTS:
      Under almost all circumstances the values of P(alpha) were closer to the E(alpha)
      than were the values of alpha. CONCLUSION: The regression models suggested by our
      analysis provide more accurate alternative p values for model-free linkage
      analysis when using the conditional logistic model.

PMID- 16612103
TI  - Effects of differential genotyping error rate on the type I error probability of
      case-control studies.
AB  - OBJECTIVES: It is well known that genotyping error adversely affects the power of
      genetic case-control association studies but there is little research on its
      effects on type I error, and none that has addressed possible differences in
      genotype error rates between cases and controls. METHODS: We used simulations to
      examine the influence of genotyping error on the type I error probability given
      by case-control studies. The effect of genotyping error on the magnitude of type
      I error was explored for a single marker of varying minor allele frequency (MAF),
      and for haplotypic tests based on two markers with varying MAF and linkage
      disequilibrium (LD) measure r(2). RESULTS: We show that even with low genotyping
      error rates (<0.01), systematic differences in the error rate between samples can
      result in type I error rates substantially above 0.05. The effect was maximal for
      markers with small MAF, markers in strong LD, and where a common allele is more
      frequently misclassified as a rare allele than vice versa. The problem was also
      exacerbated by the use of large samples. CONCLUSIONS: Our results show that small
      differential genotyping error rates between cases and controls pose significant
      problems for association analyses. Differential genotyping error rates are
      particularly likely to arise where genotype data are combined from multiple
      sites, or where case genotypes are examined against archived reference population
      cohort genotypes that are being generated in several countries. Although these
      strategies may be necessary to obtain adequately powered samples, our data show
      the importance of stringent quality control. Furthermore, associations based on
      rare haplotypes should be treated with caution.

PMID- 16612104
TI  - Effects of phytoestrogen extracts isolated from rye, green and yellow pea seeds
      on hormone production and proliferation of trophoblast tumor cells Jeg3.
AB  - BACKGROUND: Phytoestrogens are a diverse group of non-steroidal plant compounds.
      Because they have chemical structures similar to estrogens they are able to bind
      on estrogen receptors in humans. OBJECTIVES: In this study, we tested the effects
      of crude phytoestrogen extracts from rye (Secale cereale), green pea (Pisum
      sativum) and yellow pea seeds (Pisum sativum cv.) on cell proliferation and the
      production of progesterone in trophoblast tumor cells of the cell line Jeg3.
      METHODS: Isoflavone extracts from green and yellow pea seeds and lignan extracts
      from rye seeds were obtained, using different extraction methods. Isolated
      extracts were incubated in different concentrations with trophoblast tumor cells.
      Untreated cells were used as controls. At designated times, aliquots were removed
      and tested for estradiol and progesterone production. In addition, we tested the
      effects of the phytoestrogen extracts on cell proliferation. RESULTS: Cell
      proliferation is significantly inhibited by potential phytoestrogens isolated
      from rye, green and yellow pea seeds in trophoblast tumor cells of the cell line
      Jeg3. We found a correlation between the effects of proliferation and production
      of estradiol in isoflavone extracts from green and yellow pea seeds in Jeg3
      cells. In addition, higher concentrations of isoflavones isolated from green pea
      seeds and lignans from rye showed also a inhibition of progesterone production
      whereas higher concentrations of rye lignans elevated estradiol production in
      Jeg3 cells. CONCLUSION: A useful indicator test system for potential
      phytoestrogens could be established. Based on the obtained results it is proposed
      that green and yellow pea seeds contain measurable concentrations of isoflavones
      and rye seeds contain lignans which can be isolated and used for special human
      diet programs.

PMID- 16612105
TI  - Pamidronate: Treatment for severe hypercalcemia in neonatal subcutaneous fat
      necrosis.
AB  - BACKGROUND: Subcutaneous fat necrosis (SCFN) of the newborn is an uncommon
      disorder that occurs in the first weeks of life after foetal distress. It can be
      complicated by potentially life-threatening hypercalcemia. Treatments of
      hypercalcemia have included hydration, furosemide and corticosteroids. Only one
      report has described the use of intravenous bisphosphonates for this condition.
      We propose that pamidronate could be the first line therapy for severe
      hypercalcemia in SCFN. PATIENTS AND RESULTS: Four newborns presented between 2001
      and 2004 with SCFN complicated by severe hypercalcemia. At diagnosis, ionized
      calcium levels were higher than 1.4 mmol/l and were associated with high urinary
      calcium/creatinine ratios and high 1,25-dihydroxyvitamin D levels. Despite
      treatment with IV fluids, low calcium diet and furosemide, calcium levels
      remained high. The patients were given 3-4 doses (0.25-0.50 mg/kg/dose) of
      pamidronate. Urinary calcium/creatinine ratios and calcium levels decreased
      within 48-96 h. 1,25-dihydroxyvitamin D levels normalized with resolution of the
      skin lesions. No persistent nephrocalcinosis was observed. CONCLUSION:
      Pamidronate is effective, well-tolerated in the short-term and obviates the need
      for prolonged treatment with furosemide and corticosteroids. To prevent
      nephrocalcinosis, pamidronate might be considered as first line treatment for
      severe hypercalcemia in SCFN.

PMID- 16612106
TI  - Reduced serum acylated ghrelin levels in patients with hyperthyroidism.
AB  - BACKGROUND AND OBJECTIVE: Recent studies have revealed that circulating ghrelin
      levels seem to play a role in energy homeostasis. The effect of hyperthyroidism
      on ghrelin levels is not fully known. METHODS: Serum levels of ghrelin and its
      relationship with insulin resistance were evaluated in 48 patients with
      hyperthyroidism and 43 euthyroid healthy controls. Thyroid hormones, insulin,
      glucose, ghrelin levels and lipid parameters were measured in all subjects.
      Insulin sensitivity was determined using the homeostasis model assessment.
      RESULTS: Serum ghrelin levels were significantly decreased in hyperthyroid
      patients than in controls (32.5 +/- 23.3 vs. 54.1 +/- 35.5 pg/ml, p < 0.001).
      Circulating ghrelin levels significantly correlated with age (r = -0.26, p =
      0.01), fasting glucose (r = -0.21, p = 0.01), free triiodothyronine (r = -0.18, p
      = 0.04), free thyroxine (r = -0.23, p = 0.02) and thyroid stimulating hormone (r
      = 0.21, p = 0.04), but not with blood pressure, body mass index, lipid
      parameters, insulin and homeostasis model assessment (p > 0.05). Multiple
      regression analysis revealed glucose level to be the most important predictor of
      circulating ghrelin level. CONCLUSION: These results indicate that
      hyperthyroidism has effect on serum ghrelin levels. Further studies are needed
      for the exact mechanism.

PMID- 16612107
TI  - Understanding the biology and therapeutic consequences of being born small for
      gestational age. Proceedings of SGA 2005, Montreux, Switzerland, 18-20 September
      2005.

PMID- 16612108
TI  - The consequences of being born small - an adaptive perspective.
AB  - Absolute definitions of fetal growth are being replaced by definitions that focus
      on an optimal life-course trajectory. The fetus makes responses to its
      environment that are determined by the maternal macro-environment, health and
      physiology. The processes of maternal constraint create significant variations
      within the normal range of maternal environments and function, and in the fetal
      environment, which are reflected in different patterns of growth. Deficient
      nutrient provision may induce immediate adaptation in the form of fetal growth
      impairment, but will also induce adaptive responses that have evolved for
      predictive advantage; that is, for a later phase of the life cycle. This latter
      class of response, probably mediated by epigenetic processes, explains many
      outcomes of a less-than-optimal pregnancy, including impaired growth, increased
      visceral obesity, impaired cognitive development, advanced maturation and a
      greater risk of metabolic and related disease in later life. While these adaptive
      processes evolved and were appropriate in the environments of prehistory, they
      are increasingly mismatched with modern environments. Such considerations suggest
      different approaches to intervention and prevention in population-specific
      contexts.

PMID- 16612109
TI  - New definition of small for gestational age based on fetal growth potential.
AB  - Accurate definition of small for gestational age (SGA) is essential for antenatal
      as well as postnatal care. SGA is associated with significant antenatal and
      postnatal pathology. The term, however, includes constitutional smallness, and it
      is essential to adjust for physiological variation in order to identify those
      babies who are pathologically small. Maternal height, weight, parity, ethnic
      origin and the baby's gender have all been found to be significantly associated
      with normal variation in birth weight. These variables need to be adjusted for to
      calculate the true growth potential, which can be represented as individually
      customized fetal growth curves and birth weight percentiles (www.gestation.net).
      This method for calculating growth potential has been validated in a number of
      international studies. 'Customized SGA' defines neonates with intrauterine growth
      restriction, while 'small-normal' does not represent increased risk. Currently,
      coefficients are being developed for more ethnic groups, to broaden the
      international applicability of individualized standards. Work is also underway to
      incorporate the customized birth weight percentile as the starting point of
      infant growth curves.

PMID- 16612110
TI  - Normal and abnormal fetal growth.
AB  - The fetal origins of adult disease hypothesis suggests that poor intrauterine
      growth is associated with an increased risk of cardiovascular disease. The
      hypothesis goes on to implicate different growth 'phenotypes', particularly
      disproportionate growth, in the determination of the type of cardiovascular
      disease that develops. Analysis of the antenatal growth of a low-risk pregnancy
      population does not identify such growth phenotypes within the general
      population. Rather, intrauterine growth is characterized by poor predictability
      of subsequent size, suggesting that centile crossing is a common feature of
      intrauterine growth. Furthermore, there is a sexually dimorphic pattern to this
      growth that needs to be considered in further work to test the fetal origins
      hypothesis.

PMID- 16612111
TI  - Hormonal regulation of fetal growth.
AB  - Fetal growth is a complex process depending on the genetics of the fetus, the
      availability of nutrients and oxygen to the fetus, maternal nutrition and various
      growth factors and hormones of maternal, fetal and placental origin. Hormones
      play a central role in regulating fetal growth and development. They act as
      maturational and nutritional signals in utero and control tissue development and
      differentiation according to the prevailing environmental conditions in the
      fetus. The insulin-like growth factor (IGF) system, and IGF-I and IGF-II in
      particular, plays a critical role in fetal and placental growth throughout
      gestation. Disruption of the IGF1, IGF2 or IGF1R gene retards fetal growth,
      whereas disruption of IGF2R or overexpression of IGF2 enhances fetal growth. IGF
      I stimulates fetal growth when nutrients are available, thereby ensuring that
      fetal growth is appropriate for the nutrient supply. The production of IGF-I is
      particularly sensitive to undernutrition. IGF-II plays a key role in placental
      growth and nutrient transfer. Several key hormone genes involved in embryonic and
      fetal growth are imprinted. Disruption of this imprinting causes disorders
      involving growth defects, such as Beckwith-Wiedemann syndrome, which is
      associated with fetal overgrowth, or Silver-Russell syndrome, which is associated
      with intrauterine growth retardation. Optimal fetal growth is essential for
      perinatal survival and has long-term consequences extending into adulthood. Given
      the high incidence of intrauterine growth retardation and the high risk of
      metabolic and cardiovascular complications in later life, further clinical and
      basic research is needed to develop accurate early diagnosis of aberrant fetal
      growth and novel therapeutic strategies.

PMID- 16612112
TI  - Genetic variations and normal fetal growth.
AB  - Size at birth is said to be a highly heritable trait, with an estimated 30-70% of
      the variability a result of genetics. Data from family studies may be confounded,
      however, by potential interactions between fetal genes and the maternal uterine
      environment. Overall, the maternal environment tends to restrain fetal growth,
      and this is most evident in first pregnancies. Restraint of fetal growth appears
      to be inherited through the maternal line. Potential genetic candidates include
      the mitochondrial DNA 16189 variant, and common variants of exclusively
      maternally expressed genes, such as H19, which have been associated with size at
      birth. Maternal blood glucose levels and blood pressure are also correlated with
      size at birth, but the degree to which these changes relate to genetic variation
      in the mother is unclear. Elegant studies in mouse knockout models and rare
      genetic variants in humans have highlighted the importance of insulin-like growth
      factor I (IGF-I), IGF-II, insulin and their respective receptors in determining
      fetal growth. However, data linking common variation in the genes that regulate
      these proteins and receptors with size at birth are few and inconsistent.
      Interestingly, common variation in the insulin gene (INS) variable number tandem
      repeats, which regulates the transcription of insulin and IGF-II, has been
      associated with size at birth, largely in second and subsequent pregnancies,
      where maternal restraint is least evident. This suggests that fetal genes, and in
      particular paternally expressed genes, may have significant effects on fetal
      growth during pregnancies where maternal restraint of fetal growth is less
      evident.

PMID- 16612113
TI  - Regulation of maternal metabolism by pituitary and placental hormones: roles in
      fetal development and metabolic programming.
AB  - This review outlines the regulation of maternal metabolism by hormones, cytokines
      and growth factors, highlighting recent studies that implicate disordered
      somatolactogen signalling in the pathogenesis of perinatal growth failure and the
      development of the metabolic syndrome.

PMID- 16612114
TI  - Imprinted genes, placental development and fetal growth.
AB  - In mammals, imprinted genes have an important role in feto-placental development.
      They affect the growth, morphology and nutrient transfer capacity of the placenta
      and, thereby, control the nutrient supply for fetal growth. In particular, the
      reciprocally imprinted Igf2-H19 gene complex has a central role in these
      processes and matches the placental nutrient supply to the fetal nutrient demands
      for growth. Comparison of Igf2P0 and complete Igf2 null mice has shown that
      interplay between placental and fetal Igf2 regulates both placental growth and
      nutrient transporter abundance. In turn, epigenetic modification of imprinted
      genes via changes in DNA methylation may provide a mechanism linking
      environmental cues to placental phenotype, with consequences for development both
      before and after birth. Changes in expression of imprinted genes, therefore, have
      major implications for developmental programming and may explain the poor
      prognosis of the infant born small for gestational age and the wide spectrum of
      adult-onset diseases that originate in utero.

PMID- 16612115
TI  - Maternal lipid metabolism and placental lipid transfer.
AB  - During early pregnancy, long-chain polyunsaturated fatty acids (LC-PUFA) may
      accumulate in maternal fat depots and become available for placental transfer
      during late pregnancy, when the fetal growth rate is maximal and fetal
      requirements for LC-PUFAs are greatly enhanced. During this late part of
      gestation, enhanced lipolytic activity in adipose tissue contributes to the
      development of maternal hyperlipidaemia; there is an increase in plasma
      triacylglycerol concentrations, with smaller rises in phospholipid and
      cholesterol concentrations. Besides the increase in plasma very-low-density
      lipoprotein, there is a proportional enrichment of triacylglycerols in both low
      density lipoproteins and high-density lipoproteins. These lipoproteins transport
      LC-PUFA in the maternal circulation. The presence of lipoprotein receptors in the
      placenta allows their placental uptake, where they are hydrolysed by lipoprotein
      lipase, phospholipase A(2) and intracellular lipase. The fatty acids that are
      released can be metabolized and diffuse into the fetal plasma. Although present
      in smaller proportions, maternal plasma non-esterified fatty acids are also a
      source of LC-PUFA for the fetus, their placental transfer being facilitated by
      the presence of a membrane fatty acid-binding protein. There is very little
      placental transfer of glycerol, whereas the transfer of ketone bodies may become
      quantitatively important under conditions of maternal hyperketonaemia, such as
      during fasting, a high-fat diet or diabetes. The demands for cholesterol in the
      fetus are high, but whereas maternal cholesterol substantially contributes to
      fetal cholesterol during early pregnancy, fetal cholesterol biosynthesis rather
      than cholesterol transfer from maternal lipoproteins seems to be the main
      mechanism for satisfying fetal requirements during late pregnancy.

PMID- 16612116
TI  - Size at birth, postnatal growth and risk of obesity.
AB  - Epidemiological studies over the last 15 years have shown that size at birth,
      early postnatal catch-up growth and excess childhood weight gain are associated
      with an increased risk of adult cardiovascular disease and type 2 diabetes. At
      the same time, rising rates of obesity and overweight in children, even at pre
      school ages, have shifted efforts towards the identification of very early
      factors that predict risk of subsequent obesity, which may allow early targeted
      interventions. Overall, higher birth weight is positively associated with
      subsequent greater body mass index in childhood and later life; however, the
      relationship is complex. Higher birth weight is associated with greater
      subsequent lean mass, rather than fat mass. In contrast, lower birth weight is
      associated with a subsequent higher ratio of fat mass to lean mass, and greater
      central fat and insulin resistance. This paradoxical effect of lower birth weight
      is at least partly explained by the observation that infants who have been growth
      restrained in utero tend to gain weight more rapidly, or 'catch up', during the
      early postnatal period, which leads to increased central fat deposition. There is
      still debate as to whether there are critical early periods for obesity: does
      excess weight gain during infancy, childhood or even very early neonatal life
      have a greater impact on long-term fat deposition and insulin resistance? Early
      identification of childhood obesity risk will be aided by identification of
      maternal and fetal genes that regulate fetal nutrition and growth, and postnatal
      genes that regulate appetite, energy expenditure and the partitioning of energy
      intake into fat or lean tissue growth.

PMID- 16612117
TI  - Hormonal regulation of postnatal growth in children born small for gestational
      age.
AB  - Children born small for gestational age (SGA) are at high risk of permanent short
      stature, with approximately 10% continuing to have stature below the third
      centile throughout childhood and adolescence and into adulthood. The mechanisms
      involved in catch-up growth, and those that prevent catch-up growth, are still
      unknown. To date, no reliable anthropometric or endocrine parameter predictive of
      postnatal catch-up growth has been identified. However, subtle abnormalities in
      the growth hormone-insulin-like growth factor axis, the hypothalamic-pituitary
      adrenal axis and thyroid function have been described, and a mechanism involving
      intrauterine programming of hypothalamic-pituitary function has been proposed.

PMID- 16612118
TI  - Growth and the premature baby.
AB  - There is considerable evidence to show that babies born prematurely have poor
      postnatal growth, and the more premature the baby, the greater the impairment is
      likely to be and the longer it will persist. Nutrition has been shown to play an
      important part in this, but adequate nutrition is difficult, if not impossible,
      to achieve in these infants. In the most immature infants, growth retardation may
      continue for many months and catch-up may be delayed and incomplete. Evidence
      from long-term studies suggests that preterm infants will be shorter and lighter
      than term controls and that reduced stature and head size may be linked with
      lower intelligence. Although there is evidence linking better growth to better
      neurodevelopmental outcome, with reports suggesting that this can be achieved
      with dietary manipulation, there are also data that suggest that there could be a
      link between increased postnatal growth and increased morbidity and mortality in
      later childhood and adult life. Here, we provide an overview of current
      understanding of growth impairment in infants born prematurely and the effects in
      later life.

PMID- 16612119
TI  - Perinatal nutrition and hormone-dependent programming of food intake.
AB  - It is increasingly accepted that alterations of the intrauterine and early
      postnatal nutritional, metabolic and hormonal environment may predispose
      individuals to development of diseases in later life. Results from studies of the
      offspring of diabetic mothers strongly support this hypothesis. It has also been
      suggested that being light at birth leads to an increased risk of the metabolic
      syndrome (Syndrome X) in later life (the Barker hypothesis). The
      pathophysiological mechanisms that underlie this programming are unclear.
      However, hormones are important environment-dependent organizers of the
      developing neuroendocrine-immune network, which regulates all the fundamental
      processes of life. Hormones can act as 'endogenous functional teratogens' when
      present in non-physiological concentrations, induced by alterations in the
      intrauterine or neonatal environment during critical periods of perinatal life.
      Perinatal hyperinsulinism is pathognomic in offspring of diabetic mothers. Early
      hyperinsulinism also occurs as a result of early postnatal overfeeding. In rats,
      endogenous hyperinsulinism, as well as peripheral or intrahypothalamic insulin
      treatment during perinatal development, may lead to 'malprogramming' of the
      neuroendocrine systems regulating body weight, food intake and metabolism. This
      results in an increased disposition to become obese and to develop diabetes
      throughout life. Similar malprogramming may occur due to perinatal
      hypercortisolism and hyperleptinism. With regard to 'small baby syndrome' and the
      thrifty phenotype hypothesis, we propose that early postnatal overfeeding of
      underweight newborns may substantially contribute to their long-term risk of
      obesity and diabetes. In summary, a complex malprogramming of the central
      regulation of body weight and metabolism may provide a general aetiopathogenetic
      concept, explaining perinatally acquired disposition to later disease and,
      thereby, opening a wide field for primary prevention.

PMID- 16612120
TI  - Regulation of fat storage via suppressed thermogenesis: a thrifty phenotype that
      predisposes individuals with catch-up growth to insulin resistance and obesity.
AB  - Catch-up growth during infancy and childhood is increasingly recognized as a
      major risk factor for later development of insulin-related complications and
      chronic diseases, namely abdominal obesity, type 2 diabetes and cardiovascular
      disease. As catch-up growth per se is characterized by insulin resistance,
      hyperinsulinaemia and an accelerated rate of fat storage (i.e., catch-up fat)
      even in the absence of hyperphagia, the possibility arises that suppressed
      thermogenesis in certain organs/tissues - for the purpose of enhancing the
      efficiency of catch-up fat - also plays a role in the pathophysiological
      consequences of catch-up growth. Here, the evidence for the existence of an
      adipose-specific control of thermogenesis, the suppression of which contributes
      to catch-up fat, is reviewed. Recent findings suggest that such suppression of
      thermogenesis is accompanied by hyperinsulinaemia, insulin resistance in skeletal
      muscle and insulin hyperresponsiveness in adipose tissue, all of which precede
      the appearance of excess body fat, central fat distribution and elevations in
      intramyocellular triglyceride or circulating lipid concentrations. These findings
      underscore a role for suppressed thermogenesis per se as an early event in the
      pathophysiology of catch-up growth. It is proposed that, in its evolutionary
      adaptive role to spare glucose for the rapid rebuilding of an adequate fat
      reserve (for optimal survival capacity during intermittent famine), suppressed
      thermogenesis in skeletal muscle constitutes a thrifty phenotype that confers to
      the phase of catch-up growth its high sensitivity to the development of insulin
      resistance and hyperinsulinaemia. In the context of the complex interactions
      between earlier reprogramming and a modern lifestyle characterized by nutritional
      abundance and low physical activity, this thrifty 'catch-up fat phenotype' is a
      central event that predisposes individuals with catch-up growth to abdominal
      obesity, type 2 diabetes and cardiovascular disease.

PMID- 16612121
TI  - Nutrition, glucocorticoids and pancreas development.
AB  - Low birth weight is strongly predictive of hypertension, cardiovascular diseases,
      obesity, insulin resistance and diabetes. The mechanisms by which fetal
      undernutrition and, hence, low birth weight increase the risk of developing these
      diseases are unclear. To investigate the hypothesis of a primary defect in beta
      cell development, we designed a rat model of undernutrition, involving an overall
      reduction in maternal food intake. In this model, fetuses with intrauterine
      growth retardation have a decreased beta-cell mass, which persists into adulthood
      and ultimately causes glucose intolerance, thereby mimicking features of the
      metabolic syndrome. Maternal undernutrition causes elevations in glucocorticoid
      concentrations, which, in turn, cause a reduction in beta-cell mass in the fetus.
      Our data also suggest a key role of glucocorticoids when nutrient supply is
      normal. By combining in-vitro studies with in-vivo investigations in mice lacking
      the glucocorticoid receptor in the whole organism or in specific pancreatic cell
      populations, we have shown that the glucocorticoid receptor is critical for
      ensuring pancreatic architecture and survival, as well as for beta-cell mass
      expansion during a critical developmental window. Glucocorticoids act on
      precursor cells before the onset of hormone gene expression and are likely to
      programme beta-cell differentiation by modifying the balance of specific
      transcription factors, mostly Pdx-1. Glucocorticoids should therefore be
      considered as important hormones in pancreatic development, in situations of both
      normal nutrition and undernutrition. To investigate whether this is also the case
      in human pancreatic development, we studied the expression of the glucocorticoid
      receptor and that of the transcription factor Pdx-1 on pancreatic specimens from
      very early to late stages of development of the human embryo. In terms of beta
      cell ontogeny, expression of the glucocorticoid receptor in the pancreas
      coincides with that of the transcription factor Pdx-1 in beta cells. These
      results are consistent with a possible role for glucocorticoids during human
      pancreatic development.

PMID- 16612122
TI  - Early influences on the tempo of puberty.
AB  - Fetal growth retardation appears to be associated with an increased risk of
      premature adrenarche, early puberty, polycystic ovary syndrome and associated
      fertility problems. In a rat model of intrauterine growth retardation, based on
      ligation of the uterine arteries, the onset of puberty was delayed in female
      pups, with anovulation during the first cycle. The ovaries showed a lower number
      of follicles. The onset of puberty was also delayed in male pups. Testosterone
      production was lower in these growth-retarded rats compared with controls. The
      relationship between birth weight and the onset of puberty and pubertal
      progression in different cohorts of healthy children has been examined. In girls,
      no differences were observed in timing and progression of puberty, including age
      of menarche, between groups of different birth weights. In boys, a relatively
      delayed onset of puberty was observed in those with low birth weight, with a
      normally timed progression. In children with low birth weight, particularly boys,
      higher dehydroepiandrosterone levels were found compared with children with a
      normal birth weight, indicating an overactive adrenal gland in children with low
      birth weight. These data indicate that impaired fetal growth may have long
      lasting effects on pubertal development. The fact that results of human studies
      on the relationship between fetal growth and the onset of puberty are often
      controversial may be explained by the heterogeneity of children born small for
      gestational age with respect to the intrauterine insult that they experience.
      From rat studies, it is clear that a serious intrauterine insult associated with
      growth failure can lead to dysregulation of puberty and gonadal function.

PMID- 16612123
TI  - Puberty after prenatal growth restraint.
AB  - There is increasing evidence for a link between prenatal growth and pubertal
      development. Here we highlight a selection of pubertal characteristics in
      children who were born small for gestational age (SGA). Boys born SGA are at risk
      of high levels of follicle-stimulating hormone (FSH) and low levels of inhibin B
      and a small testicular volume during adolescence. In girls born SGA, the age at
      pubertal onset and the age at menarche are advanced by about 5-10 months;
      prenatal growth restraint may also be associated with higher FSH levels and
      smaller internal genitalia in adolescence. The ovulation rate was found to be
      reduced in adolescent girls born SGA, and an insulin-sensitizing therapy was
      capable of raising this low ovulation rate. Menarche is definitely advanced in
      girls born SGA with precocious pubarche and in those with an early-normal onset
      of puberty. Current evidence suggests that insulin resistance is a key mechanism
      linking a post-SGA state to early menarche; hence, insulin sensitization may
      become a valid approach to prevent early menarche and early growth arrest in
      girls born SGA.

PMID- 16612124
TI  - Low birth weight and male reproductive function.
AB  - Scientific interest in morbidity in children born small for gestational age (SGA)
      has increased considerably over the last few decades. The elevated risk of
      cardiovascular and metabolic diseases in adulthood in individuals born SGA has
      been well documented, whereas data on gonadal development are limited.
      Prospective studies, case-control investigations and registry surveys show that
      impaired intrauterine growth increases the risks of congenital hypospadias,
      cryptorchidism and testicular cancer approximately two- to threefold. Although
      few studies focus on the effect of intrauterine growth on male pubertal
      development, testicular hormone production or sperm quality, available evidence
      points towards a subtle impairment of both Sertoli cell and Leydig cell function.
      Animal studies support the hypothesis that impaired perinatal growth restriction,
      depending on the timing, can affect postnatal testis size and function into
      adulthood. Current human data, however, are often based on highly selected
      hospital populations and lack precise distinctions between low birth weight, SGA,
      timing of growth restriction and a differentiation of catch-up growth patterns.
      Despite the methodological inadequacies of individual study results, the combined
      evidence from all data leaves little doubt that fetal growth restriction is
      associated with increased risk of male reproductive health problems, including
      hypospadias, cryptorchidism and testicular cancer.

PMID- 16612125
TI  - Small for gestational age and the metabolic syndrome: which mechanism is
      suggested by epidemiological and clinical studies?
AB  - The metabolic and cardiovascular complications associated with in-utero
      undernutrition have been identified during the past 10 years. Reduced fetal
      growth is independently associated with an increased risk of development of
      cardiovascular diseases, the insulin-resistance syndrome or one of its components
      (i.e., hypertension, dyslipidaemia, impaired glucose tolerance and type 2
      diabetes). Insulin resistance appears to be a key component underlying these
      metabolic complications. Although the mechanism remains unclear, several pieces
      of evidence support an active role of adipose tissue in the emergence of insulin
      resistance (an abnormal growth pattern and repartition, hypersensitivity to
      catecholamines, regulation of leptin and adiponectin secretion and modulation of
      peroxisome proliferator-activated receptor gamma). Among individuals born SGA,
      those who are more at risk of gaining excess adiposity are those who are thin at
      birth following a period of fetal growth restriction. This period of
      undernutrition is followed by a neonatal period of catch-up growth and
      renutrition. This pattern induces important modifications in adipose tissue, with
      long-term consequences, among which is a high risk of early development of
      insulin resistance. Not all individuals born SGA will show such modifications in
      adipose tissue, meaning that not all of those born SGA are at risk of insulin
      resistance and diabetes. From a broader point of view, several hypotheses have
      been proposed over the past 10 years to explain this unexpected association
      between being born SGA and the later development of disease. Each of them points
      to a detrimental fetal environment, to a genetic susceptibility or to
      interactions between these two components playing a critical role in this
      context. Although not confirmed, the hypothesis suggesting that this association
      could be the consequence of genetic/environmental interactions remains the most
      attractive.

PMID- 16612126
TI  - Prematurity and insulin sensitivity.
AB  - Premature infants of low and extremely low birth weight represent a challenge for
      neonatal intensive care units and paediatricians. These neonates may be at
      increased risk of insulin resistance and diabetes perinatally and during
      childhood. During the first week of postnatal life, infants born prematurely are
      at risk of abnormalities in glucose homeostasis. Additionally, there are major
      differences in their glucose/insulin homeostasis compared with infants born at
      term. Preterm infants are at risk of hypoglycaemia, due to decreases in deposits
      of glycogen and fat that occur during the third trimester, and also to transient
      hyperinsulinaemia. Hyperglycaemia may also be observed in preterm infants during
      the perinatal period. These infants are unable to suppress glucose production
      within a large range of glucose and insulin concentrations, insulin secretory
      response is inappropriate, insulin processing is immature and there is an
      increased ratio of the glucose transporters Glut-1/Glut-2 in fetal tissues, which
      limits sensitivity and hepatocyte reaction to increments in glucose/insulin
      concentration during hyperglycaemia. In addition, increased concentrations of
      tumour necrosis factor alpha present in intrauterine growth retardation (IUGR)
      and induce insulin resistance. It has been proposed that the reduced insulin
      sensitivity may result from adaptation to an adverse in utero environment during
      a critical period of development. We have investigated postnatal insulin
      resistance in 60 children born with very low birth weight and either small for
      gestational age or at an appropriate size for gestational age. This study showed
      that IUGR, rather than low birth weight itself, was associated with increased
      fasting insulin levels. As poor fetal growth may be associated with the
      development of obesity, type 2 diabetes and the metabolic syndrome in later life,
      it is important that we continue to increase our understanding of the effects of
      IUGR on postnatal growth and metabolism.

PMID- 16612127
TI  - Metabolic aspects of insulin resistance in individuals born small for gestational
      age.
AB  - Numerous studies have shown an association between low weight at birth and being
      born small for gestational age (SGA) on the one hand and risk of developing
      insulin resistance and type 2 diabetes on the other. Our studies in twins have
      indicated a non-genetic age-dependent origin of insulin resistance and type 2
      diabetes associated with being born SGA. In order to gain insight into the
      molecular metabolic defects and mechanisms linking SGA with insulin resistance
      and type 2 diabetes, we performed a series of experiments in young and elderly
      twins, and, in particular, in young men (aged 19-23 years) with a weight at birth
      at term in the lowest 10th percentile with no family history of diabetes. The
      control group included age-matched men with birth weights at term in the upper
      normal range. While body mass index and waist-to-hip ratios were similar in the
      individuals born SGA and controls, dual-energy X-ray absorptiometry studies
      documented a higher degree of abdominal obesity in the men who had a low weight
      at birth. Using the gold standard hyperinsulinaemic-euglycaemic clamp technique
      combined with glucose tracers and studies of forearm glucose uptake, we found an
      impairment of insulin-stimulated glycolytic flux and reduced forearm (muscle)
      glucose uptake in the face of normal whole-body glucose uptake. In addition, we
      found a significantly decreased insulin secretion rate during oral glucose
      ingestion after correction for insulin action (disposition index), a paradoxical
      enhanced insulin suppression of hepatic glucose production and lower fasting
      plasma glycerol levels, suggesting impaired lipolysis. Finally, analysis of
      skeletal muscle biopsies showed reduced muscle expression of several key proteins
      involved in insulin signalling and glucose transport, including protein kinase C
      zeta, the two subunits of phosphoinositol 3-kinase (i.e., p85alpha and p110beta)
      and the insulin-sensitive glucose transporter, Glut-4, in individuals of low
      birth weight. In conclusion, being born SGA and of low birth weight is associated
      with type 2 diabetes in a non-genetic manner, and programming of muscle insulin
      action and signalling represents an early mechanism responsible for this
      association.

PMID- 16612128
TI  - Growth hormone therapy in short children born small for gestational age.
AB  - There is still a lack of data from randomized, controlled, long-term studies of
      growth hormone (GH) treatment in children born small for gestational age (SGA),
      but the available evidence indicates consistently that GH therapy is a valid
      growth-promoting treatment in these children, particularly if started early.
      Whilst side effects appear uncommon, ongoing surveillance is required and treated
      children should be monitored for changes in glucose homeostasis, lipid profiles
      and blood pressure, especially during puberty. We provide an update on the safety
      and efficacy of GH treatment in short children born SGA.

PMID- 16612129
TI  - Safety of growth hormone treatment in children born small for gestational age:
      the US trial and KIGS analysis.
AB  - BACKGROUND: Recently, growth hormone (GH) therapy for children with short stature
      born small for gestational age (SGA) has been approved in the USA and Europe.
      There have been few reports examining adverse events during GH treatment of these
      children. AIMS: (i) To examine glucose tolerance and insulin sensitivity during
      GH treatment of children born SGA in a US trial. (ii) To determine and compare
      adverse events reported in children born SGA with those reported in children with
      idiopathic short stature (ISS) enrolled in KIGS - Pfizer International Growth
      Database. METHODS: In the US SGA trial, an oral glucose tolerance test was
      performed and fasting plasma glucose, insulin and glycosylated haemoglobin
      (HbA(1C)) concentrations were measured at baseline and after 12 months of GH
      therapy. Insulin sensitivity was calculated using the homeostasis model
      assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI).
      In the KIGS analysis, a retrospective audit of spontaneously logged cumulative
      adverse events in children born SGA and those with ISS was undertaken. Adverse
      events are reported per 1,000 patients. Values are expressed as mean with 10th
      90th percentiles. RESULTS: In the US trial, 84 patients had complete data sets
      for analysis. Median birth weight was 1.78 kg (SDS, -2.5) and birth length 43 cm
      (SDS, -2.2) at a median gestational age of 36.5 weeks; 79% were Caucasian. At
      entry, median age of the patients analysed was 6.6 years, and 65% were male.
      Median height was 104.3 cm (SDS, -2.97), median weight 15.95 kg (SDS, -2.21) and
      body mass index 14.66 kg/m(2) (SDS, -0.67). No patients developed impaired
      glucose tolerance or overt diabetes mellitus. The 0-min glucose concentration was
      81 mg/dl at baseline and 86 mg/dl at 1 year, while the 120-min glucose
      concentration was 90 mg/dl at baseline and 96 mg/dl at 1 year. The 0-min insulin
      concentrations were 2.9 mU/l at baseline and 5.3 mU/l at 1 year, while the 120
      min insulin levels were 7.7 mU/l at baseline and 11 mU/l at 1 year. The
      proportions of HbA(1C) were 5.2 and 5.4% at baseline and 1 year, respectively.
      HOMA and QUICKI values were 0.59 and 0.42, respectively, at baseline, and 1.13
      and 0.38 at 1 year. In KIGS, there were 1909 children born SGA aged 9.1 (3.9
      13.3) years with a birth weight SDS of -2.6 (-4.0 to -1.5), birth length SDS of 
      2.7 (-4.3 to -1.3) and height SDS of -2.71 (-3.9 to -1.8) prior to treatment. GH
      doses ranged from 0.032 to 0.037 in the USA and from 0.022 to 0.023 mg/kg/day in
      the remaining countries in KIGS. Neither total (187 vs. 183) nor serious (14 vs.
      10) adverse events occurred more commonly in the SGA group than in the ISS group.
      Although respiratory adverse events occurred more commonly in children born SGA
      (34.3 vs. 16.8; p < 0.05), endocrine (12.0 vs. 2.7; p < 0.05) and hepatobiliary
      (6.2 vs. 1.1; p < 0.05) adverse events occurred more commonly in children with
      ISS. CONCLUSIONS: As expected, a reduction in insulin sensitivity occurred during
      GH treatment of children born SGA; however, glucose tolerance remained normal. No
      adverse events were reported more commonly in children born SGA than in those
      with ISS. Minor differences in adverse events reporting within organ systems
      between children born SGA and those with ISS are probably due to variable under
      reporting of adverse events. GH appears to be a safe drug to use at current doses
      as a growth-promoting agent in short children born SGA.

PMID- 16612131
TI  - Signal transduction induced by opioids in immune cells: a review.
AB  - New data regarding signal transduction triggered by opioid ligands in immune
      cells are reviewed, and the signal transduction in neuronal cells is documented.
      Similar signaling pathways are induced by opioids in immune as well as neuronal
      cells. Opioids altered second messenger cAMP, intracellular calcium, and second
      messenger-induced kinases in immune cells. Met-enkephalin, preferentially delta
      opioid, was bimodally regulated, while kappa-opioids inhibited these second
      messengers. delta-, kappa- and micro-opioids altered nitric oxide secretion,
      inducing cGMP as the second messenger in immune cells. Coupling of opioid
      agonists to opioid receptors activated mitogen-activated protein/extracellular
      signal-regulated protein kinases and various transcription factors in immune
      cells. Activator protein 1 (AP-1), c-fos, and nuclear factor-kappaB (NF-kappaB)
      are transcription factors shared by neuronal and immune cells. Delta-opioids
      activated AP-1, c-fos, activating transcription factor 2, Ikaros-1 and Ikaros-2
      transcription factors in immune cells. Induction of kappa-opioid receptor gene by
      retinoic acid resulted in increased binding of Sp1 transcription factor to the
      promoter of the kappa-opioid receptor. Micro-opioids inhibited synthesis of
      common transcription factors AP-1, c-fos, NF-kappaB, and nuclear factor of
      activated T cells in activated or stimulated immune cells, whereas micro-opioids
      activated NF-kappaB, GATA-3, and Kruppel-like factor 7 transcription factors in
      non-stimulated immune cells.

PMID- 16612132
TI  - Relation between laterality and immune response after acute cerebral ischemia.
AB  - OBJECTIVE: During the last 2 decades, right/left hemisphere dominance was
      supposed to affect the immune system differently. Experimental and clinical
      observations indicate that the left hemisphere plays a crucial role in the
      development of the immune system. The true relationship between immune response
      and acute ischemic stroke laterality remains to be elucidated. METHODS: We
      studied acute right-handed stroke patients admitted to a single acute neurology
      department with a specialized stroke unit. Being part of our clinical protocol,
      blood samples were taken within the first 24 h after the onset of stroke
      symptoms. The medical record of each patient was reviewed, and demographic,
      clinical laboratory (key criteria: C-reactive protein, CRP, and white blood cell
      count, WBC) and neuroimaging information was retrieved. All data were presented
      descriptively, and bivariate test statistics, ANOVA (log-transformed data) or
      linear correlations were calculated. RESULTS: Fifty-six of the 187 patients
      admitted to our Stroke Unit between October 2003 and March 2004 with different
      stroke subtypes according to the TOAST criteria were retrospectively evaluated in
      order to characterize the impact of stroke laterality on immunoregulatory
      response measured by CRP levels and WBC. Correlation analysis revealed that left
      sided ischemic stroke yielded a significantly higher correlation between CRP
      levels and WBC. Following left-sided stroke, a more marked variability in CRP and
      WBC was found compared to patients with right-sided ischemic stroke, although
      ANOVA did not show significant differences between immune response values as a
      function of stroke subtypes. CONCLUSIONS: We identified an association between
      stroke laterality and immunoregulatory response in patients with acute ischemic
      stroke. Left-sided stroke may be considered as a direct risk factor for
      infectious disease or immune deficits and should attract special attention.
      However, these preliminary results need be confirmed by controlled studies.

PMID- 16612133
TI  - Mouse strains differ in their susceptibility to poststroke infections.
AB  - OBJECTIVE: Severe infections, in particular pneumonia, have a major impact on the
      clinical management and outcome of stroke patients. In a mouse model we have
      recently demonstrated that stroke induces immunodepression which can result in
      life-threatening infections. Here, we investigated whether the susceptibility to
      infections after stroke is strain dependent. METHODS AND RESULTS: Mice from
      129SV, C57/B6, and Balb/C strains were subjected to experimental stroke by
      filament occlusion of the middle cerebral artery (MCAO) for 60 min. Infarct
      volumes were measured 3 days after MCAO. Microbiological assessment was based on
      cultures of bronchoalveolar lavage (BAL), lung tissue and blood of animals
      obtained 3 days after stroke. Three days after stroke 129SV mice did not only
      develop bacterial chest infection, but also had a strongly increased
      susceptibility to bacteremia. In contrast, C57BL/6 and Balb/C mice acquired
      bacterial lung infections only. In addition, bacterial load in BAL was
      significantly higher in 129SV mice than in the other mice strains. These
      differences in susceptibility to infection did not correlate with infarct
      volumes. CONCLUSIONS: Stroke-associated pneumonia developed in three commonly
      used mouse strains while severity of infections differed between strains. Since
      infections affect outcome, monitoring of infections is highly relevant for the
      interpretation of results in experimental stroke research.

PMID- 16612134
TI  - Thiamine and cyanocobalamin relieve neuropathic pain in rats: synergy with
      dexamethasone.
AB  - Treatment of neuropathic pain is an area of largely unmet medical need.
      Therefore, this pain may require the development of novel drug entities. In the
      search for alternatives, B vitamins have been found to be a clinically useful
      pharmacological tool for patients with neuropathic pain. However, preclinical
      studies supporting this use are lacking. In this study, we assessed the possible
      antiallodynic effects of thiamine, pyridoxine, and cyanocobalamin as well as
      dexamethasone and their combination on spinal nerve ligation induced allodynia.
      Sub cutaneous administration of thiamine (75-600 mg/kg), pyridoxine (75-600
      mg/kg), cyanocobalamin(0.75-6 mg/kg), and dexamethasone (4-32 mg/kg)
      significantly reduced tactile allodynia in rats. Maximal antiallodynic effects
      were reached with 600 mg/kg of thiamine (approximately 58%), 600 mg/kg of
      pyridoxine (approximately 22%), 6 mg/kg of cyanocobalamin (approximately 73%),
      and 32 mg/kg of dexamethasone (approximately 68%). Since a small antiallodynic
      effect was observed with pyridoxine, this drug was not further analyzed in the
      combinations. Coadministration of thiamine or cyanocobalamin and dexamethasone
      remarkably reduced spinal nerve ligation induced allodynia (approximately 90%),
      showing a synergistic interaction between either thiamine or cyanocobalamin and
      dexamethasone. Our data indicate that thiamine and pyridoxine as well as the
      combination of B vitamins and dexamethasone are able to reduce tactile allodynia
      in rats and suggest the possible clinical use of these drugs in the treatment of
      neuropathic pain in human beings.

PMID- 16612135
TI  - Posttraumatic syndromes in children and adolescents after road traffic accidents-
      a prospective cohort study.
AB  - BACKGROUND: The impact of road traffic accidents (RTAs) on the physical health of
      children is well recognized, but their psychological consequences have only
      recently become a topic of research. While other traumatic experiences in
      childhood are well studied, this kind of trauma has been poorly investigated to
      date. SAMPLING AND METHODS: A prospective cohort study was conducted of 8- to 18
      year-old children and adolescents who were involved in RTAs in a large urban area
      during a 6-month period. The children and adolescents were interviewed within 1
      week after the accident and, again, 3 months later. In total, 72 children and
      adolescents took part in the study. Symptoms of posttraumatic stress, depression
      and anxiety were assessed by a structured clinical interview and standardized
      questionnaires. RESULTS: One week after the accident, 11% of the children met the
      diagnostic criteria for posttraumatic stress disorder (PTSD) according to ICD-10
      and a further 13% met the criteria for 'subsyndromal PTSD'. Complex syndromes
      consisting of subsyndromal posttraumatic stress, (separation) anxiety and
      depression were common among those children. Isolated cases of anxiety and
      depression symptoms were also observed but rarely reached an impairing level.
      Three months after the accident, 25% of the children reported persistence of the
      PTSD symptoms (measured by the Impact of Event Scale - Revised). The strongest
      predictor of the extent of posttraumatic stress after 3 months was proven to be
      the initial level of PTSD symptoms. This predictor alone accounted for 38% of its
      variance. CONCLUSIONS: Our results provide evidence that even after 'everyday'
      RTAs, psychological consequences are common. Special attention should be paid to
      the common occurrence of subsyndromal psychological disturbances and more complex
      syndromes. The results further indicate the limitations of the PTSD concept in
      the assessment of posttraumatic disturbances in childhood and adolescence.

PMID- 16612136
TI  - Parental attachment and its impact on the development of psychiatric
      manifestations in school-aged children.
AB  - BACKGROUND: Few studies have examined the relationship between the attachment
      styles of the primary caregivers and the behavioral problems of their school-aged
      children. This study was performed to identify the impact of insecure attachment
      patterns of parents on the development of their children's psychiatric
      manifestations and disorders. SAMPLINGS AND METHODS: We included 494 2nd to 3rd
      graders and their primary caretakers. A relationship questionnaire was applied to
      identify the parental attachment patterns. We investigated the children's mental
      and behavioral problems by using the Korean Child Behavior Checklist. For
      objective psychiatric diagnoses, we interviewed 130 high-risk subjects using the
      Korean Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and
      Lifetime version. RESULTS: Those parents judged to be preoccupied had children
      with more internalized symptoms than those who were judged to be secure (p<
      0.01); dismissing/avoidant parents had children with higher scores on Attention
      problems (p = 0002), and fearful/avoidant parents had children with more
      externalized symptoms (p < 0.01). Moreover, children with insecure attachment
      type parents revealed more psychiatric morbidity than children with secure
      parents (p = 0.042). CONCLUSION: Parental insecure attachment was associated with
      the development of the psychopathologies and psychiatric illness of their
      children.

PMID- 16612137
TI  - Assessing the social behavior of unipolar depressives: the criteria for Typus
      melancholicus.
AB  - AIM: (a) To define the nuclear characteristics of the melancholic type of
      personality (TM), that in European and Japanese psychopathological tradition is
      considered the model which most accurately describes the social behavior of
      unipolar depressives, through clear, valid, and synthetic criteria (criteria for
      TM = CTM); (b) to evaluate the diagnostic power, reliability, internal
      consistency, and other psychometric properties of these criteria. METHODS:
      Personality features of 115 unipolar depressives consecutively admitted to 2
      psychiatric facilities were assessed with the CTM and with the Kasahara Scale
      (KS). Four further unipolar depressives were assessed with the CTM by 13
      different raters (11 CTM-naive and 2 experienced). RESULTS: The CTM have shown
      high reliability and internal consistency. They were also highly concordant with
      the KS scores. CONCLUSIONS: The CTM can discriminate between TMs and non-TMs and
      suggests that the TM kind of personality is not a dimensional concept but a
      coherent structure in which one feature entails the presence of all the others.

PMID- 16612138
TI  - Dystonic movement disorders and spinal degenerative disease.
AB  - The occurrence of degenerative spinal disease subsequent to dystonic movement
      disorders has been neglected and has received more attention only recently.
      Spinal surgery is challenging with regard to continuous mechanical stress when
      treatment of the underlying movement disorder is insufficient. To characterize
      better the particular features of degenerative spinal disease in patients with
      dystonia and to analyze operative strategies, we reviewed the available published
      data. Epidemiologic studies reveal that degenerative spinal disorders in patients
      with dystonia and choreoathetosis occur much earlier than in the physiological
      aging process. Dystonic movement disorders more often affect the spine at higher
      cervical levels (C(2-5)), in contrast to spinal degeneration with age which
      manifests more frequently at the middle and lower cervical spine (C(5-7)).
      Degenerative changes of the cervical spine are more likely to occur on the side
      where the chin is rotated or tilted to. Various operative approaches for
      treatment of spinal pathologies have been advocated in patients with dystonic
      movement disorders. The available data do not allow making firm statements
      regarding the superiority of one approach over the other. Posterior approaches
      were first used for decompression, but additional anterior fusion became
      necessary in many instances. Anterior approaches with or without instrumented
      fusion yielded more favorable results, but drawbacks are pseudarthrosis and
      adjacent-level disease. Parallel to the development of posterior fusion
      techniques, circumferential surgery was suggested to provide a maximum degree of
      cord decompression and a higher fusion rate. Perioperative local injections of
      botulinum toxin were used initially to enhance patient comfort with halo
      immobilization, but they are also applied in patients without external fixation
      nowadays. Treatment algorithms directed at the underlying movement disorder
      itself, taking advantage of new techniques of functional neurosurgery, combined
      with spinal surgery have recently been introduced and show promising results.

PMID- 16612139
TI  - Current state and perspectives of dendritic cell vaccination in cancer
      immunotherapy.
AB  - Recent progress in the approach towards immunotherapy of cancer consists in
      molecular definition of tumor antigens, new tools for phenotypical and functional
      characterization of tumor-specific effector cells and clinical use of novel
      adjuvants for optimal stimulation of a cancer-specific immune response such as
      dendritic cells. In spite of these advances and immunological as well as clinical
      responses in selected patients, mechanisms involved in dendritic-cell-based
      cancer immunotherapy are still poorly understood. Therefore, a standardized study
      design and small pilot trials are needed to explore open scientific questions in
      future clinical trials. This review focuses on the different parameters of
      dendritic cell biology relevant to cancer immunotherapy and on innovative
      approaches to hopefully enhance the efficacy of dendritic cell vaccination.

PMID- 16612140
TI  - Thermal behaviour of human stratum corneum. A differential scanning calorimetry
      study at high scanning rates.
AB  - PURPOSE: To use high-speed differential scanning calorimetry (DSC) in the
      identification of transitions in human stratum corneum (SC). Several scanning
      rates (100 degrees C/min to 400 degrees C/min) are used. RESULTS: Eight
      transitions from 0 to 120 degrees C are detected in a significant number of
      samples. Most of these transitions have already been identified in previous
      studies, but have been labeled considering essentially that only four are
      present. Results also indicate some degree of reversibility for transitions
      occurring at temperatures above 90 degrees C. Dehydrated SC samples displayed
      slightly more defined transition peaks and a less frequent presence of the
      transitions below 50 degrees C. In turn, the delipidised SC matrix showed two
      major endothermic signals, centered around 55 and 100 degrees C, in conjunction
      with other much less marked features. CONCLUSIONS: The interpretation of DSC
      traces in terms of four main transition temperatures must be complemented having
      in mind the occurrence of other transitions, some of them at physiological
      temperatures. This work further suggests that transitions at temperatures above
      90 degrees C may to a large degree be associated to lipids, while transition at
      approx. 55 degrees C is probably related to lipids covalently linked to proteins,
      as previously suggested.

PMID- 16612141
TI  - Reduced cellular toxicity of a new silver-containing antimicrobial dressing and
      clinical performance in non-healing wounds.
AB  - Bacterial colonisation of wounds may delay wound healing. Modern silver
      containing dressings are antimicrobial, yet cellular toxicity is a serious side
      effect. We provide data for a newly formulated silver-containing ointment
      dressing, Atrauman Ag, for antimicrobial activity and cytotoxicity. Atrauman Ag
      effectively killed a panel of commensal skin as well as pathogenic bacterial
      strains while cytotoxicity for HaCaT keratinocytes was only around 10%. With
      these favourable in vitro tests, Atrauman Ag was analysed in 86 patients with
      traumatic and non-healing wounds of different aetiologies. The wound state was
      evaluated for 3 subsequent dressing changes. The slough score was reduced from
      59.2 to 35.8%, granulation tissue increased from 27 to 40% and epithelialisation
      went up from 12.1 to 24%. We conclude that Atrauman Ag has a superior profile of
      antimicrobial activity over cellular toxicity and the low silver ion release rate
      may prevent interference with wound-healing mechanisms.

PMID- 16612142
TI  - Establishing a minimal erythema concentration of methyl nicotinate for optimum
      evaluation of anti-inflammatories.
AB  - Topical administration of chemicals such as methyl nicotinate that induce
      erythema have been employed to measure the effectiveness of formulations
      containing anti-inflammatory agents. Prior studies have utilized a single
      concentration of methyl nicotinate, between 36.5 and 100 mM, for all test
      subjects in evaluations of topical formulations. However, individuals have
      different thresholds of response to methyl nicotinate; thus, a single
      concentration may not be appropriate for all individuals and could result in the
      apparent lack of anti-inflammatory activity of the formulation being evaluated.
      In the current study, we evaluated the use of a minimal erythema concentration
      (MEC) of methyl nicotinate, defined as the lowest concentration that produces a
      complete and even erythema at the test site, compared with a 36.5-mM
      concentration of methyl nicotinate. Hydroalcoholic gels containing the
      nonsteroidal anti-inflammatory drug ibuprofen were compared with placebo. Diffuse
      reflectance spectroscopy was employed to measure differences in cutaneous
      inflammatory response between the control (placebo)-treated group and the
      ibuprofen-treated group. When chemical erythema was induced using an MEC of
      methyl nicotinate, greater reductions in erythema were seen in ibuprofen-treated
      sites compared with sites treated with a 36.5-mM concentration of methyl
      nicotinate. In conclusion, for an accurate assessment method of erythema induced
      by methyl nicotinate, consideration should be given to determining the extent of
      response of an erythema-producing agent on an individual basis. An MEC of methyl
      nicotinate should be determined and employed for each individual to obtain more
      consistent and reliable efficacy results of anti-inflammatory activity.

PMID- 16612143
TI  - Treatment of head and neck dermatitis with ciclopiroxolamine cream--results of a
      double-blind, placebo-controlled study.
AB  - In atopic dermatitis, microbial allergens may be pathogenetically significant.
      Apart from Staphylococcus aureus, these are primarily lipophilic Malassezia
      yeasts. They are particularly involved in the pathogenesis of head and neck
      dermatitis (HND), a special form of atopic dermatitis, which is often difficult
      to treat. Fifty patients (21 men, 29 women) with moderate to severe HND of at
      least 6 months' duration were included in a prospective double-blind study. All
      of them showed at least 10% involvement of the head-neck region. The severity of
      disease was evaluated by Investigator Global Assessment (IGA), Eczema Area and
      Severity Index (EASI) for the head-neck region and a pruritus score. IgE
      antibodies to Malassezia sympodialis and/or Malassezia furfur (at least CAP class
      1) were a prerequisite for study enrollment. Either 1% ciclopiroxolamine cream
      (Batrafen; Aventis Pharma, Bad Soden, Germany) or the corresponding base cream
      were thinly applied to the affected areas twice daily for 28 days. Sixteen
      patients in the ciclopiroxolamine group and 13 patients in the placebo group
      completed the study. To assess the change in severity of atopic eczema, IGA
      differences between the individual measuring points were determined for all
      patients. There were significant differences in the IGA score change between the
      ciclopiroxolamine group and the placebo group, from t3 to t4, and over the total
      period. Similar, but not significant, changes were observed with the EASI score,
      in terms of affected skin area and itching. The present study is the first to
      examine the effect of antifungal single-drug therapy with a cream containing
      ciclopiroxolamine on the course of HND. The study medication was found to be
      significantly effective. To optimize this effect, suitable patients selected in
      terms of fungal load, specific IgE, prick test and particularly atopy patch test
      for Malassezia antigens could receive combined treatment with antimycotic
      containing shampoos and/or short-term systemic antimycotic therapy in severe
      cases.

PMID- 16612144
TI  - Effect of c-Met expression on survival in head and neck squamous cell carcinoma.
AB  - The proto-oncogene c-Met has been suggested to be associated with progression of
      squamous cell carcinoma of the head and neck. The aims of the present study were
      to assess the prevalence of c-Met expression in oral squamous cell carcinoma
      (OSCC) and to verify whether c-Met can be considered a marker of prognosis in
      these patients. In a retrospective study, a cohort of 84 OSCC patients was
      investigated for c-Met expression and its cellular localization by
      immunohistochemistry. After grouping for c-Met expression, OSCC patients were
      statistically analyzed for the variables age, gender, histological grading, tumor
      node metastasis, staging and overall survival rate. Univariate and multivariate
      statistics were used for data analysis. Sixty-nine cases (82.2%) of OSCC showed
      immunopositivity, with a mainly membranous expression and scattered areas also
      showing a cytoplasmic localization, whereas 15 cases (17.8%) did not show c-Met.
      No statistical association was found between c-Met expression and any variables
      considered at baseline, apart from the higher number of c-Met positivity in
      females (p = 0.026). Among positive tumors, well-differentiated areas showed low
      or absent cytoplasmic expression, while low-differentiated areas showed both
      membranous and cytoplasmic positivity. In terms of prognostic significance, c-Met
      expression was found to have an independent association with a poorer overall
      survival rate (p = 0.036). On the basis of these results, it is possible to
      suggest c-Met as an early marker of poor prognosis, a hallmark of aggressive
      biological behavior in OSCC, suggested to be useful in identifying cases of OSCC
      before the relapse.

PMID- 16612145
TI  - Characterization of antibodies to CA 125 that bind preferentially to the cell
      associated form of the antigen.
AB  - OBJECTIVE: Antibodies to CA 125 have been used to predict relapse of ovarian
      cancer, but have performed poorly as therapeutic agents. One rationale for this
      is antibody binding to circulating shed antigen. Our aim in this study was to
      develop antibodies to human CA 125 that have enhanced selectivity for the cell
      associated form of the antigen. METHODS: Monoclonal antibodies were raised to a
      recombinant fragment of CA 125 that included sequence proximal to the putative
      membrane attachment site. Antibodies were characterized in terms of their binding
      site, affinity and selectivity for cell-associated CA 125. RESULTS: In assays
      using patient-derived CA 125, a subset of high-affinity (KD <5 nM) monoclonal
      antibodies demonstrated a 10- to greater than 200-fold increase in selectivity
      for cell-associated CA 125 when compared with controls. Based on mapping of the
      various monoclonal antibodies obtained, it was determined that shedding of CA 125
      most likely occurs in the most C-terminal repeat domain. CONCLUSION: Results from
      competition analysis using patient-derived shed antigen predict that the
      antibodies described in this study may have significantly enhanced tumor
      targeting properties when compared with existing antibodies to CA 125 in a tumor
      environment having high concentrations (>10,000 CA 125 units) of shed CA 125.

PMID- 16612146
TI  - Expression of tyrosine kinase receptors in lung carcinoids.
AB  - OBJECTIVES: Typical lung carcinoids are usually relatively benign tumors, but
      distant metastases are seen in up to 12% of the patients. In contrast, atypical
      carcinoids are more aggressive tumors, displaying metastases in up to 70%. The
      current treatment of metastatic lung carcinoids is discouraging. New therapies,
      such as inhibitors of the tyrosine kinase receptor family c-kit, platelet-derived
      growth factor receptors (PDGFR) alpha and beta and epidermal growth factor
      receptor (EGFR) have shown promising results in other malignancies and might be
      of value in malignant lung carcinoids. PATIENTS AND METHODS: Tumor tissue from 51
      patients with typical lung carcinoids were immunostained with polyclonal
      antibodies against c-kit, PDGFRalpha, PDGFRbeta and EGFR. Of the 24 patients who
      had metastatic disease, 17 had distant metastases. Fifteen of the patients had
      died from their disease. RESULTS: Twelve of the tumors stained positive for c
      kit, 44 expressed PDGFRalpha, 30 showed positive immunoreactivity for PDGFRbeta
      and 26 were EGFR immunoreactive. Among the 17 patients with distant metastases, 5
      tumors expressed c-kit, 12 were PDGFRalpha immunoreactive, 9 stained positive for
      PDGFRbeta, and 7 showed positive immunoreactivity for EGFR. There was no
      correlation to distant metastases or survival for c-kit, PDGFRbeta or EGFR.
      CONCLUSIONS: Tyrosine kinase receptors such as c-kit, PDGFRalpha, PDGFRbeta and
      EGFR are expressed in a significant number of patients with metastatic lung
      carcinoids. Treatment with inhibitors of the tyrosine kinase receptors expressed
      may be considered.

PMID- 16612147
TI  - [New treatment strategy of multiple myeloma for cure].
AB  - Multiple myeloma has long been considered an incurable disease. Indeed, the
      median survival time in patients treated with conventional chemotherapy has been
      reported to be about 3 years, and the survival rate decreased consecutively and
      was about 2 to 3% at 10 years. However, after introduction of autologous stem
      cell transplantation in the 1990s, the median survival time was improved to about
      5 years. Furthermore, novel drugs have been introduced in the treatment of
      patients with relapsed/refractory multiple myeloma, and improved the prognosis of
      these patients. Thalidomide, which has anti-angiogenetic activity, has a 30-40%
      response rate, and the combination of thalidomide and dexamethasone has a 40-50%
      response rate. Lenalidomide, which is a thalidomide analog, has a higher efficacy
      and lower incidence of adverse effects than thalidomide. Bortezomib, which is a
      proteasome inhibitor and inhibits NF-kappaB activity, has also excellent efficacy
      like thalidomide. The clinical trials using these drugs for newly diagnosed
      patients are now ongoing around the world, and show very excellent results. The
      good combination of stem-cell transplantation and novel drugs may well improve
      the prognosis of patients with multiple myeloma, and induce a cure,especially in
      young patients.

PMID- 16612148
TI  - [Brachytherapy for prostate cancer].
AB  - This review article aims to overview modern prostate brachytherapy in Japan.
      Permanent transperineal prostate brachytherapy with I-125 started in September,
      2003 in Japan. Brachytherapy has several advantages: the dose is adapted
      precisely to the tumor shape and size, and the long-lived isotope gives a higher
      tumor dose with less damage to normal tissue; less-time consuming for patients
      and staff: long-term results comparable to surgery or external beam series in the
      USA; and quality of life after brachytherapy also appealing. These advantages
      have brought about increasing use in Japan as well. Patients with a high
      probability of organ-confined disease and a low-risk group are appropriately
      treated with brachytherapy. Brachytherapy candidates with a significant risk of
      extraprostatic extension should be treated with supplemental external beam
      radiation therapy. High-dose-rate (HDR) brachytherapy with Ir-192 has preceded
      seed implants in Japan. HDR has some theoretical advantages. Long-term results of
      brachytherapy in the USA are comparable with surgery or external beam irradiation
      so far. We should develop more sophisticated brachytherapy techniques in Japan.

PMID- 16612149
TI  - [Altered fractionation].
AB  - For improving radiotherapy treatment results, altered fractionation (AF) is one
      of the most important biological factors to modify the conventional fractionation
      schedule. AF is classified into two categories. One is decreasing in dose-per
      fraction and increasing in total dose, so-called hyperfractionation (HF), which
      expands the difference in radio-sensitivity between tumor and normal tissue. On
      the other hand, shortening of overall treatment time, so-called accelerated
      hyperfractionation (AHF), prevents accelerated repopulation of tumor cells during
      radiotherapy. AF is rarely recognized as a standard therapy despite many reports
      about its efficacy against various cancers, totally. This is often used for head
      and neck cancer. However, the problem is that they usually improve local-control,
      but do not always improve survival. Although AHF is recognized as one of a
      standard treatment for small cell lung cancer, it is still objectionable and
      disputable. Besides these, efficacy of AF against non-small cell lung cancer,
      bladder cancer and malignant glioma, has been reported. However, AF is not
      considered as a standard treatment. Accompanied with spread out of stereotactic
      irradiation, dose-fractionation-time relationship becomes to be more important
      subject, especially hypofractionation, to clarify the new aspect of AF.

PMID- 16612150
TI  - [Intensity Modulated Radiation Therapy (IMRT)].
AB  - Radiotherapy plays an important role in the management of cancer patients, and
      half of the patients with malignant tumors are treated with radiotherapy in the
      United States. In Japan, the necessity of radiation therapy has come to be widely
      acknowledged in cancer treatment, and more and more cancer patients are being
      treated with radiation. External beam radiation is the most-used radiotherapy at
      the present time. The advantage is that this treatment modality can be used in a
      short time, although the problem is that not only the cancer lesion but also the
      surrounding normal tissue is irradiated,causing an adverse effect on normal
      tissue. In order to solve this problem,treatments such as 3D-Conformal Radiation
      Therapy (3D-CRT), Intensity Modulated Radiation Therapy (IMRT), Stereotactic
      Radiation Surgery (SRS) and Stereotactic Radiation Therapy (SRT) are clinically
      used as an extremely precise radiotherapy, thanks to the advances in computer
      technology in recent years. Therefore, the purpose of these extremely precise
      radiation therapies is to administer a high dose to the tumor intensively, and to
      suppress quantities of magnetism to normal tissues. IMRT treatment results for
      prostate cancer patients and head and neck cancer patients are reportedly better
      than with other irradiation methods. In this chapter,we explain the external
      irradiation method with the focus on IMRT and the extremely precise radiotherapy
      preformed in the Tokyo Women's Medical University Hospital.

PMID- 16612151
TI  - [Clinical experience of carbon ion radiotherapy for malignant tumors].
AB  - The carbon ion (C-ion) beams provide unique advantageous biological and physical
      properties in radiotherapy (RT) for malignant tumors. C-ion beams have a high
      relative biological effectiveness (RBE) resulting from the high linear energy
      transfer (LET). In terms of their physical characteristics, C-ion beams exhibit a
      spread-out Bragg peak (SOBP) and make for a better dose distribution of the
      target volume by specified beam modulations. Between June 1994 and August 2005, a
      total of 2,371 patients with malignant tumors were registered in phase I/II dose
      escalation studies and clinical phase II trials using C-ion beams generated at
      Heavy Ion Medical Accelerator in Chiba (HIMAC). In the initial dose-escalation
      studies, grade 3 or more late rectal complications had developed in some
      patients. However, the adverse effects were resolved because of the use of
      appropriate dose levels and modification of the radiation technique. C-ion beams
      can carry out hypofractionated radiotherapy with a large fraction dose and reduce
      the overall treatment times compared with conventional radiotherapy. They can
      also achieve better local tumor control even for radio-resistant tumors such as
      malignant melanoma, hepatocellular carcinoma and bone and soft tissue sarcomas
      with minimal morbidity to the normal surrounding tissues.

PMID- 16612152
TI  - [Proton beam therapy].
AB  - Proton beam therapy (PBT) has made it possible to deliver a higher concentration
      of radiation to the tumor by its Bragg-peak, and is easy to utilize due to the
      fact that its biological characteristics are identical with X-rays. PBT has a
      half-century history, and more than 40,000 patients have been reported as having
      had treatments with proton beams worldwide. The historic change to this therapy
      occurred in the 1990s, when the Loma Linda University Medical Center began its
      clinical activity as the first hospital in the world to utilize a medically
      dedicated proton therapy facility. Since then, similar hospital-based medically
      dedicated facilities have been constructed. Results from around the world have
      shown the therapeutic superiority of PBT over alternative treatment options for
      ocular melanoma, skull base sarcoma, head & neck cancer, lung cancer,esophageal
      cancer, hepatocellular carcinoma, and prostate cancer. PBT is expected to achieve
      further advancement both clinically and technologically.

PMID- 16612153
TI  - [Stereotactic body radiotherapy (SBRT)].
AB  - The techniques of three-dimensional conformal radiotherapy (3 D-CRT) and patient
      immobilization have recently been developed, enabling us to focus high doses on
      the target with relatively less irradiation of normal tissues. In radiotherapy
      for solitary lung tumors, the local control may be safely improved by delivering
      a higher dose at only the target volume using these techniques. Recently, several
      clinical studies on stereotactic body radiotherapy (SRT) using the 3 D-CRT
      technique for solitary lung tumors have been reported. The single dose used is 10
      15 Gy, and the total sessions are three to five. The local control rate is more
      than 90% and complication rates are very low. Therefore, this treatment is a
      promising new non-invasive treatment for early stage lung cancer. A multi
      institutional clinical study, JCOG 0403, in now underway.

PMID- 16612154
TI  - [Change of creatinine clearance rate in accordance with aging in Japanese
      patients with head and neck cancer].
AB  - Most of the head and neck tumors are squamous cell carcinomas (SCCs), which are
      relatively sensitive to chemotherapeutic agents. Cis-platinum (CDDP), 5
      fluorouracil and taxanes are widely used worldwide for SCCs, and CDDP is the most
      common agent. Renal toxicity is a well-known adverse effect of CDDP, and adequate
      pre and post-hydration or combined administration of neutralizing agents is
      performed during CDDP injection. Before the CDDP administration, we have to
      evaluate renal function of the patients using creatinine clearance rate (Ccr). In
      Japan, CDDP at the dose of 60-70 mg/m(2)/day is administered in cases with over
      65 ml/min/1.73 m(2) of Ccr, whereas in cases under 60 ml/min/1.73 m(2), we use
      other drugs, e.g., carboplatin, to prevent the renal dysfunction followed by
      chemotherapy. In other countries, the dose of CDDP is 70-100 mg/m(2)/day, and the
      discrepancy is based on the poor renal function of Japanese. We calculated Ccrs
      of 107 head and neck cancer patients since January, 2004 to August, 2005, and
      evaluated renal function before any treatment. Ccr was decreased in proportion to
      aging. At the age of fifties, 43.5% of the patients indicated lower Ccr than 65
      ml/min/1.73 m(2): sixties, 45.7%; seventies, 50.0%; and eighties, 85.7%. In the
      United States, the average glomerular filtration rate of over 70 year-old healthy
      people is estimated as 75 ml/min/ 1.73 m(2), and it is considered sufficient
      kidney function for the administration of CDDP at the dose of 70-100 mg/
      m(2)/day. The incident rate of end-stage renal disease is 1.3 times higher in the
      United States than in Japan. The incident rate of diabetes, which is the main
      cause of renal dysfunction, is almost the same in both countries. Though the
      reason is unclear, it is the fact that the renal function of Japanese decreases
      quickly in accordance with aging.

PMID- 16612155
TI  - [Gefitinib as a first-line therapy in patients with advanced non-small cell lung
      cancer].
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity
      of gefitinib as a first-line therapy in patients with advanced non-small cell
      lung cancer (NSCLC). METHODS: We analyzed 19 patients with advanced NSCLC
      retrospectively, who were treated with gefitinib as a first-line therapy. These
      patients were not considered for systemic chemotherapy secondary to co-morbid
      conditions, poor performance status (PS) or refusal of chemotherapy. RESULTS:
      Median age 68 years, male/female 10/9, stage III/IV 7/12, smoker/non-smoker 12/7,
      adenocarcinoma/non-adeno 13/6, PS 0/1/2/3/4 0/4/7/5/3. Four patients had a
      partial response and the overall response rate was 21.0%. The median survival
      time was 6.8 months and 1-year survival was 27%. Overall toxicities were mild.
      Grade (G) 3 diarrhea was observed in one patient and G1 interstitial pneumonia in
      one. CONCLUSIONS: These results demonstrate that gefitinib is active as a first
      line therapy in patients with advanced NSCLC.

PMID- 16612156
TI  - [Combination chemotherapy with carboplatin and weekly Paclitaxel in patients with
      advanced non-small cell lung cancer].
AB  - BACKGROUND: The objective of this study was to evaluate the efficacy and toxicity
      of carboplatin plus weekly paclitaxel as first-line therapy in patients with
      advanced non-small cell lung cancer (NSCLC). METHODS: Forty-nine patients were
      analyzed retrospectively. Every 4 weeks patients received 70 mg/m(2)paclitaxel on
      days 1, 8, and 15, and AUC 5-6 carboplatin on day 1. RESULTS: A median of four
      cycles (range, 1-7) was administered. Twenty-four patients had a partial
      response, and the overall response rate was 48.9%. The median survival time was
      12.8 months and the 1-year survival was 50.7%. Overall toxicities were mild. The
      most common toxicity was neutropenia, grade 3/4 in 32% of the patients. Grade 3/4
      hematologic toxicities included anemia (16%) and thrombocytopenia (8%). Grade 3/4
      non-hematologic toxicities included febrile neutropenia (2%), pneumonia (10%) and
      interstitial pneumonia (2%). Grade 2 peripheral neuropathy was seen in one
      patient (2%). CONCLUSIONS: These results demonstrate that this regimen is an
      active and tolerable treatment for patients with advanced NSCLC. It is suggested
      that this weekly regimen should be considered as one of the standard therapies
      for future chemotherapy in advanced NSCLC.

PMID- 16612157
TI  - [Experimental chemotherapy against human esophageal carcinoma xenografts with TS
      1, cisplatin and docetaxel].
AB  - Three strains of human esophageal carcinoma xenografts established in our
      institution were tested against combination chemotherapy in vivo and in vitro. TS
      1 plus cisplatin (CDDP) was shown to be an effective combination against two
      carcinoma strains of moderately-differentiated type. Determination of the
      thymidylate synthase (TS) demonstrated a higher inhibition of the enzyme by
      adding CDDP to 5-FU, suggesting biochemical modulation. The remaining strain of
      poorly-differentiated type was resistant to the combination and an attempt was
      made to add docetaxel (DTX) to show that the three-drug combination was effective
      against the strain. Combination chemotherapy including TS-1 and CDDP thus appears
      to be useful treatment choice for esophageal carcinoma.

PMID- 16612158
TI  - [Clinicopathological significance of orotate phosphoribosyltransferase in gastric
      carcinoma].
AB  - Orotate phosphoribosyltransferase (OPRT EC 2.4.2.10) is a key enzyme related to
      the first-step phosphorylation process of 5-fluorouracil. We have recently
      developed an ELISA system to measure OPRT levels in cancerous tissues. We
      examined OPRT levels in 75 gastric carcinoma tissues using this ELISA, and the
      relationships with clinicopathologic factors were evaluated. A total of 75
      surgically-resected gastric carcinoma tissues were subjected to the present
      study. The intratumoral OPRT level was determined by a newly-developed enzyme
      linked immunosorbent assay (ELISA). Enzyme activities of OPRT were also
      determined using a conventional enzyme assay using radiolabeled 5-fluorouracil as
      a substrate. OPRT levels in gastric carcinoma tissues measured by ELISA were
      5.4+/-3.6 ng/mg protein, ranging from 0.2 to 15.7 ng/mg protein. There was a
      significant correlation between the OPRT level measured by the ELISA and OPRT
      enzyme activity (y=0.545x - 0.017, r(2)=0.617, p<0.0001). OPRT levels were
      significantly higher in patients with differentiated type and invasive type of
      gastric carcinoma, whereas OPRT levels were not associated with the pathological
      stage of gastric carcinoma. These results suggest that OPRT levels were related
      to the histopathological characteristics of gastric carcinoma, and may be related
      to the response to fluoropyrimidine-based anticancer chemotherapy.

PMID- 16612159
TI  - [Successful chemotherapy with carboplatin and docetaxel for an elderly patient
      with advanced non-small cell lung cancer].
AB  - A 79-year-old man was admitted to our hospital with right hypochondrium pain. His
      chest X-ray and CT scan showed a mass lesion on the left upper lobe, and multiple
      metastases in the liver. The diagnosis was non-small cell carcinoma of the lung.
      He received 4 courses of combined chemotherapy of carboplatin and docetaxel every
      4 weeks. At the end of 4 courses, a partial response was achieved. Two courses of
      a in similar regimen were added at the time of a later recurrence, and the effect
      was a partial response. Carboplatin+docetaxel combined chemotherapy, which can be
      conducted relatively safely on an outpatient basis, may be an effective treatment
      for non-small cell lung cancer in the elderly.

PMID- 16612160
TI  - [A case of complete response in a primary lesion treated by gefitinib for two
      years after surgery of brain metastasis from lung cancer].
AB  - A 54-year-old woman was admitted to our hospital for vertigo, headache and
      vomiting at the end of July, 2001. Under a diagnosis of cerebellar tumor and
      right lung tumor, she underwent a resection of cerebellar tumor on August 7,
      2001. The histopathological diagnosis was "metastatic adenocarcinoma". Lung
      cancer was doubted as for the origin, however, she did not want further
      examination. The patient was given 2 courses of postoperative chemotherapy
      (CBDCA+VNR) and radiotherapy (50 Gy), and discharged. Gefitinib treatment was
      begun in September, 2002 at her request. The tumor marker was not elevated, and
      the tumor size on CT showed the tendency toward some reduction. Close examination
      including PET revealed no metastasis. The patient then underwent right upper
      lobectomy (ND 2 a) on October 8, 2004 at her request. Histopathologically,
      psammoma body existed but no cancer cells nor lymph node metastasis. It seemed
      that there was a complete response by gefitinib after 3 years.

PMID- 16612161
TI  - [A case of adenocarcinoma of the lung significantly responding to TS-1 plus
      cisplatin combination chemotherapy].
AB  - A 67-year-old man was admitted to our hospital, complaining of productive cough
      and chest pain. Chest radiograph and computed tomography revealed a huge mass
      invading the mediastinum, enlargement of right hilar and cardiophrenic lymph
      nodes and nodules in right lower lobe and left upper lobe. Multiple space
      occupying regions in the liver were also observed. Cytology for exfoliated sputum
      revealed adenocarcinoma, so he was diagnosed with advanced lung cancer (clinical
      stage T 4 N 2 M 1, stage IV). He was enrolled in a clinical phase II study, and
      received combination chemotherapy with TS-1 and cisplatin. TS-1 was administered
      on days 1-21. Cisplatin was administered on day 8. Every cycle was repeated every
      5 weeks. The patient then received 6 cycles of chemotherapy,and yielded a partial
      response (87% decrease in size determined by RECIST criteria version 2. 0). Grade
      2 leukopenia and neutropenia were observed, and non-hematologic toxicities were
      also mild. The disease progressed after the end of chemotherapy, and he was given
      5 regimens of chemotherapy, including gefitinib. He died of brain metastases.
      Time to progression of his disease for combination chemotherapy using TS-1 and
      cisplatin chemotherapy was 240 days. Survival time was 709 days. This combination
      chemotherapy was effective in the present case, and might prolong survival. We
      think it is valuable to confirm the efficacy of TS-1 and cisplatin combination
      chemotherapy.

PMID- 16612162
TI  - [Successful treatment for advanced hepatocellular carcinoma by hepatic arterial
      infusion of CDDP powder as second-line chemotherapy].
AB  - A 72-year-old man with type C liver cirrhosis had suffered from hepatocellular
      carcinoma (HCC) since April, 2001. HCC spread diffusely all over the right lobe
      of his liver, and the serum alpha-fetoprotein (AFP) value increased up to 42,696
      ng/ml in June of 2004. He was implanted with a port-catheter system, and hepatic
      arterial infusion chemotherapy (HAIC) using low-dose of CDDP and 5-FU was
      started. However, it was not effective and after 4 months, the serum AFP level
      increased up to 755,030 ng/ml, ascites appeared, and gastro-esophageal varices
      also spread. No definite metastasis was detected, then we started to second-line
      chemotherapy. He was then given HAIC using CDDP powder for intraarterial use
      (CDDP 50 mg/m(2)/20 min, monthly). After 3 courses, the serum AFP level decreased
      to 9 10 ng/ml, and abdominal CT revealed that the main tumor had regressed and
      ascites had disappeared. After one more course, the serum AFP value decreased to
      8 ng/ml and complete response was achieved on abdominal CT imaging. There was no
      major complication related to the chemotherapy. HAIC for advanced HCC using LFP
      has been reported to achieve favorable results, but no other regimens have been
      proved to the standard for HCC. HAIC using CDDP powder for advanced HCC may be
      beneficial as the second-line chemotherapy.

PMID- 16612163
TI  - [A case of scirrhous gastric cancer responding to TS-1/CDDP neoadjuvant
      chemotherapy].
AB  - A 72-year-old female with scirrhous-type advanced gastric cancer was treated with
      TS-1/CDDP as neoadjuvant chemotherapy. TS-1 (80 mg/m(2)/day) was orally
      administered for 3 weeks and CDDP (60 mg/m(2)) was administered by intravenous
      drip on day 8. Partial response (PR) was obtained after the first course, and
      total gastrectomy was performed. The histological diagnosis revealed complete
      disappearance of cancer cells in the stomach and a few regional lymph node
      metastases (3/67). The patient has now been in good health without a recurrence
      for 1 year and 9 months after surgery.

PMID- 16612164
TI  - [A case of gastric cancer with multiple liver metastases resistant to TS-1
      responding to chemotherapy with paclitaxel plus doxifluridine].
AB  - A 74-year-old man was revealed to have type 3 gastric cancer with synchronous
      multiple liver metastases. Despite treatment with TS-1 (120 mg/body), an increase
      in tumor size was demonstrated by computer tomography and endoscopy. We tried a
      course of a combination chemotherapy consisting of paclitaxel (PTX) plus
      doxifluridine (5'-DFUR ) to reduce the tumor. 5'-DFUR (600 mg/m(2)) was
      administered day 1 to 14 followed by 7 days'rest as one course. PTX (80 mg/m(2))
      was infused on days 1 and 8. After 5 courses, the tumor markers decreased
      markedly, and computer tomography and endoscopy revealed remarkable tumor
      reduction which was thought to show a partial response. After 13 courses we
      discontinued this chemotherapy, so increase of the tumor marker was remarkable.
      This case suggests that PTX/5'-DFUR protocol is effective for clinical management
      of gastric cancer resistant to TS-1.

PMID- 16612165
TI  - [Successful bi-weekly paclitaxel treatment of an AFP-producing gastric cancer
      patient with peritoneal dissemination and multiple liver metastasis].
AB  - The patient was a 71-year-old man. Chemotherapy was conducted in two courses
      combining TS-1 (120 mg) and CDDP (80 mg) under the diagnosis of AFP-producing
      gastric cancer with multiple liver metastasis and peritoneal dissemination.
      Peritoneal dissemination disappeared, liver metastasis almost disappeared after
      completion of two courses, and the therapeutic efficacy was rated as PR. Then,
      the patient underwent distal gastrectomy and lymph node dissection. He received
      TS-1 monotherapy after surgery, but his condition gradually became worse. TS-1
      and CDDP combination were given again, but an ileus resulted due to peritonitis
      carcinomatous. We therefore administered bi-weekly paclitaxel (80 mg/m(2))
      intravenously. The ileus disappeared after one week, liver metastatic lesions and
      ascites were improved after completion of one course, and therapeutic efficacy
      was rated as PR. Grade 3 neutropenia and grade 1 alopecia occurred, but no other
      adverse reaction occurred. This therapy made it possible to eat foods, conduct
      chemotherapy safely while ambulatory. Paclitaxel can be expected to show good
      therapeutic efficacy and improve QOL of a peritonitis carcinomatosa patient with
      TS-1 resistant advanced gastric cancer.

PMID- 16612166
TI  - [A case of advanced colon cancer with metastases to both para-aortic lymph nodes
      and cervical vertebrae effectively treated by TS-1 therapy].
AB  - The patient was a 68-year-old woman who had cecal cancer with para-aortic lymph
      node metastases. Ileocecal resection was performed palliatively. Since metastasis
      to cervical vertebrae was detected after the operation, she received radiation
      therapy of 14 Gy to improve neck pain. Chemotherapy with TS-1 (80 mg/day) was
      started on an outpatient basis (4 weeks administration followed by a 2-week drug
      free period). After 4 courses of this chemotherapy, metastases to both para
      aortic lymph nodes and cervical vertebrae were remarkably reduced on CT and PET.
      Throughout the period of treatment, there was no adverse effect and this
      treatment has been maintained. In conclusion, this case seems significant from
      the viewpoint of achieving a partial response to TS-1 and maintaining a high
      quality of life. Moreover,we identified the presence of TS and DPD using an
      immunohistochemical staining technique. The primary tumor was positive for DPD
      stain test and negative for TS stain test. It was suggested that this cancer
      especially would respond to TS-1 chemotherapy.

PMID- 16612167
TI  - [Pancreatic acinar cell carcinoma successfully treated with combination of oral
      TS-1 and intra-arterial cisplatin].
AB  - Pancreatic acinar cell carcinomas are rare, and little is reported on their
      chemotherapy. We report a 49-year old male patient with pancreatic acinar cell
      carcinoma and multiple liver metastases, which responded to oral TS-1 and hepatic
      arterial infusion of cisplatin. The patient underwent a partial hepatectomy, MCT
      abrasions and excision of the pancreatic tumor. Postoperative pathological
      studies revealed metastases of acinar cell carcinoma to the liver and lymph
      nodes; the primary lesion was undetermined. After surgery, the patient was
      treated with hepatic arterial infusion of cisplatin and oral TS-1. Metastatic
      tumors completely disappeared, and serum lipase decreased to normal levels.
      Abdominal CT one year after surgery revealed a pancreatic body tumor, which was
      surgically removed. Pathological studies showed primary pancreatic acinar cell
      carcinoma, while previous metastases remained under control. To summarize, TS-1
      and cisplatin can be effective treatments for pancreatic acinar cell carcinomas.

PMID- 16612168
TI  - [Efficacy of controlled-release oxycodone for dyspnea in cancer patients--three
      case series].
AB  - Dyspnea is a common symptom in patients with advanced cancer. Systemic morphine
      administration has been reported as an effective pharmacological treatment to
      control dyspnea. However, there have been few reports on similar effects of
      alternative opioids except for morphine. To evaluate the effect of controlled
      release oxycodone on the relief of dyspnea, we investigated three cases with
      opioid substitution from subcutaneous morphine to oral oxycodone. In all cases,
      both opioids provided equivalent effects for the palliation of cancer dyspnea
      with no significant adverse effects. Future studies in the appropriate clinical
      designs will be needed to confirm our findings.

PMID- 16612170
TI  - Bibliography. Current world literature. Personality disorders and neuroses.

PMID- 16612169
TI  - [Clinical trials of vnorelbine in breast cancer--its scientific usefulness and
      development history until regulatory approval].
AB  - Vinorelbine, a novel vinca alkaloid derivative developed in France, has been
      widely used for the treatment of breast cancer and non-small cell lung cancer
      since the 1990s in many foreign countries. In Japan, it has been available for
      the treatment of non-small cell lung cancer since 1999, and the additional
      indication of breast cancer was approved in May 2005. Japanese phase I clinical
      trials started in 1988. A total of six trials have been conducted in patients
      with advanced or recurrent breast cancer, and have provided evidence of efficacy
      in all groups of patients, including those receiving vinorelbine as first-line
      monotherapy and those previously treated with both anthracyclines and taxanes.
      This report reviews the data from these studies and also presents the results of
      combination therapy evaluated outside Japan. In addition,we explain why it took
      17 years for vinorelbine to be approved despite the fact that as early as the
      beginning of development, it was scientifically proven to be very useful in
      patients with breast cancer, and that the new drug application was submitted in
      1993. The relationship between healthcare professionals, patients and the
      regulatory agency is also discussed to point out related issues.

PMID- 16612171
TI  - Mood patterns and classification in bipolar disorder.
AB  - PURPOSE OF REVIEW: The aim of this review is to highlight recent studies that
      have questioned the current split of mood disorders into the categories of
      bipolar and depressive disorders. RECENT FINDINGS: A continuity between bipolar
      disorders (mainly bipolar II disorder) and major depressive disorder was
      supported by several lines of evidence: depressive mixed states (mixed
      depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the
      same episode do not support the splitting between mania/hypomania and
      depression); family history, major depressive disorder is the most common mood
      disorder in relatives of bipolar probands; lack of points of rarity between the
      depressive syndromes of bipolar II disorder and major depressive disorder;
      bipolar features in major depressive disorder; major depressive disorder shifting
      to bipolar disorders; history of manic/hypomanic symptoms in major depressive
      disorder and correlation between lifetime manic/hypomanic symptoms and depressive
      symptoms in major depressive disorder; factors of hypomania inside major
      depressive disorder; recurrent course of major depressive disorder; depression
      more common than mania and hypomania in bipolar disorders; trait mood lability in
      major depressive disorder. SUMMARY: This review of the recent findings on the
      relationship between bipolar disorders (especially bipolar II disorder) and
      depressive disorders seems to support a continuity among mood disorders, and runs
      against the current classification of mood disorders dividing them into
      independent categories. Further research is needed in the area, in part because
      of its possible treatment impact.

PMID- 16612172
TI  - Classification and treatment of sub-threshold depression.
AB  - PURPOSE OF REVIEW: The purpose of this review is to evaluate the recent
      literature on depressive spectrum disorders. RECENT FINDINGS: Research into so
      called 'minor' forms of depression has moved beyond efforts justifying these
      entities and describing their components to an exploration of the impact of
      depressive spectrum disorders on health, quality of life, and as a predisposing
      factor for major depressive disorder. As with major depression, pharmacological
      and psychosocial interventions may be useful treatments. Researchers have begun
      to examine the nature of depressive spectrum disorders in specific populations,
      such as the elderly and the medically ill. SUMMARY: Sub-threshold forms of
      depression are becoming a focus of research at a time when quality of life and
      prevention of serious mental illness are being recognized as important public
      health concerns. Individuals with depressive spectrum disorders are at an
      increased risk of developing major depressive disorder and are more likely to
      have a history of episodes of depression. The challenges confronting psychiatric
      researchers include developing a consensus about diagnosis of depressive spectrum
      disorders and ways to measure their severity, and increasing public recognition
      of the impact of the entire spectrum of depression in order to facilitate the
      discovery of appropriate treatments.

PMID- 16612173
TI  - Depression and neurological disorders.
AB  - PURPOSE OF REVIEW: Clinical studies support a bidirectional link between
      depression and neurological diseases. Here we review the most recent findings
      supporting the hypothesis that major depression is a medical illness of the brain
      which can be elicited by neurological illnesses. RECENT FINDINGS: In the last
      year major improvements in brain-imaging techniques allowed correlations to be
      demonstrated between functional and structural brain abnormalities in specific
      brain areas (prefrontal cortex, hippocampus, cingulate gyrus) and the presence
      and severity of affective disorders, thus suggesting a neural basis for their
      onset and progression. Similar lesions, caused by neurological diseases, have
      been found to correlate with the presence of depression in neurological
      illnesses, but literature on the topic is still lacking. Depression in
      neurological disorders responds to the same treatments available for idiopathic
      major depression, but patients seem to have different sensitivities to side
      effects depending on their specific neurological syndrome. Most available data
      come from case reports and open trials. SUMMARY: 'Psychiatric' and 'neurologic'
      depression seem to share common abnormalities in specific brain areas, but sound
      brain-imaging studies of the neural correlates of depression in neurological
      disorders are still lacking. Available treatments are efficacious, but no clear
      cut guidelines about the best drugs and dosages can be defined because double
      blind placebo-controlled studies are still scarce.

PMID- 16612174
TI  - Depression, pain, and somatoform disorders.
AB  - PURPOSE OF REVIEW: The frequent co-occurrence of depression and somatic symptoms
      poses a continuing challenge to clinicians, researchers and experts involved in
      drawing up classifications. In this review we present recently published
      literature on aspects of epidemiology, classification and treatment in this
      important overlap area. RECENT FINDINGS: From the multitude of papers published
      annually on the co-occurrence of different pain conditions and depression,
      temporomandibular dysfunction stands out this year by sheer quantity; it can be
      seen as a model case of the necessity for differentiated high-quality assessments
      on the biological as well as the psychosocial level. There is a general move to
      separate utility of diagnostic classifications from their validity, and this
      strengthens classificatory approaches that help to view the regular overlap of
      depression, pain and other somatic symptoms as the rule rather than the
      exception. The incorporation of cognitive variables like causal attributions
      should help to distinguish clinically relevant subtypes among overlap cases. The
      classificatory future of the category of 'somatoform disorders' is somewhat in
      doubt, but reforms seem to be more productive than abolishment.
      Psychopharmacology provides rather intense recent coverage of the overlap field,
      with newer dual serotonergic-noradrenergic reuptake inhibitors offering some
      promise. SUMMARY: Treating the overlap of depression, pain and other somatic
      symptoms as the rule rather than the exception is necessary for adequate
      aetiological research as well as for diagnosis and treatment, with one
      dimensional classificatory and treatment approaches almost certainly being
      insufficient.

PMID- 16612175
TI  - An update on regional brain volume differences associated with mood disorders.
AB  - PURPOSE OF REVIEW: Structural brain changes are apparent in some magnetic
      resonance imaging studies of patients with mood disorders, but results are
      inconsistent. The focus of this review is to examine whether there are
      demographic or clinical characteristics of people with mood disorders that are
      associated with regional brain volume changes. A systematic search of the
      literature in English, from January 2004 to July 2005, was performed on MEDLINE.
      References cited in all reports were searched iteratively to identify missing
      studies. RECENT FINDINGS: Recent studies have focused on factors that might help
      to reconcile the divergent reports of regional brain volume changes in major
      depressive disorder and bipolar disorder. Small hippocampal volumes are apparent
      in patients with recurrent major depressive disorder, but not generally reported
      early in the course of adult onset depression. Small hippocampal volumes may be
      apparent in patients with childhood onset illness. Small hippocampal volumes are
      infrequently reported in bipolar disorder, but studies to date have not accounted
      for illness history or treatment status. Changes in amygdala volumes are
      inconsistently reported in patients with major depressive disorder or bipolar
      disorder. There are relatively fewer reports of other brain regions, including
      the areas of the frontal cortex and striatum. An extensive preclinical literature
      suggests that various psychotropic medications may have neurotrophic and
      neuroprotective effects, making documentation of treatment history essential.
      SUMMARY: Patients' age, sex, age at onset of disease, course of illness and
      treatment status may affect the detection of regional brain volume changes in
      people with mood disorders.

PMID- 16612176
TI  - Emotional information processing in mood disorders: a review of behavioral and
      neuroimaging findings.
AB  - PURPOSE OF REVIEW: A relatively long history of research has shown that mood
      disorders are associated with abnormalities in the processing of emotional
      stimuli. Only the most recent studies, however, have begun to elucidate the
      specificity and neural basis of these abnormalities. This article reviews and
      discusses the results of these studies. RECENT FINDINGS: Individuals diagnosed
      with major depressive disorder exhibit an attentional bias toward negative
      emotional cues (e.g. sad faces), an attentional bias away from positive emotional
      cues (e.g. happy faces), and an enhanced memory for negative emotional material.
      Compared with healthy controls, individuals with major depressive disorder show
      increased neural activity in response to sad faces and diminished neural activity
      in response to happy faces in emotion-related brain circuits (e.g. amygdala and
      ventral striatum). Some of these abnormalities in the processing of emotional
      information persist after symptom remission and they have also been found in
      healthy individuals who are at heightened risk for the development of mood
      disorders. SUMMARY: The reviewed data show that major depressive disorder
      involves specific abnormalities in the cognitive and neural processing of
      emotional information and that these abnormalities may potentially contribute to
      the vulnerability for negative emotion and onset of depressive episodes.

PMID- 16612177
TI  - Psychodynamic psychotherapy in the treatment of mood disorders.
AB  - PURPOSE OF REVIEW: This article summarizes recent studies of psychodynamic
      psychotherapy for mood disorders. It is important to note whether the therapy
      studied is adhering to the principles of psychodynamic psychotherapy, whether it
      is manual based or flexibly responsive to patient developments, whether it is
      short term or long term and whether it is combined with pharmacotherapy. RECENT
      FINDINGS: A review of recently published studies has found that all studies show
      a significant improvement in symptoms in patients who were depressed before
      treatment with psychodynamic psychotherapy. It is rare, however, for a study to
      meet the criteria of randomized clinical trials: use of treatment manuals and
      assured adherence, a sample of patients specifically diagnosed with depression
      and relevant measures. In one metaanalysis of studies meeting the above criteria,
      two of 17 studies included a sample with a diagnosis of depression, and short
      term psychodynamic psychotherapy achieved similar results as other
      psychotherapies. Naturalistic studies show improvement with dynamic psychotherapy
      over time in both symptoms and dynamic measures, such as defense styles and
      frustration tolerance. SUMMARY: In the last year there were few randomized
      controlled studies specifically examining psychodynamic psychotherapy for mood
      disorders. Most evidence from naturalistic and various efficacy studies indicates
      that dynamic psychotherapy, with or without pharmacotherapy, is associated with
      improvement in symptoms and some character features. Longer follow-ups provide
      useful data for what can be a chronic or recurring illness. There are no data
      showing that psychodynamic therapy is more or less effective than other forms of
      psychotherapy.

PMID- 16612178
TI  - Adherence to treatment in mood disorders.
AB  - PURPOSE OF REVIEW: Nonadherence to medication is common in mood disorders.
      Improving adherence should decrease risk of relapse, improve outcome and lessen
      costs. Here we review recent qualitative and quantitative work in this area.
      RECENT FINDINGS: Themes that emerged from qualitative studies for nonadherence
      are discomfort about psychiatric diagnoses, including denial of the illness,
      problematic side effects, fears around dependency and the view that medication
      was unhelpful following resolution of the acute phase. The psycho-educational
      intervention model alone has shown little improvement in adherence. The
      collaborative managed care model for improving outcomes in depression in primary
      care is of limited benefit in increasing adherence or indeed outcomes.
      Psychological approaches have been most successful when concentrating on the
      patient-clinician alliance when attitudes and experience are explored,
      recognizing the importance of the patient's opinion in treatment decisions.
      Psycho-pharmaceutical interventions such as changing medication preparations have
      potential efficacy. SUMMARY: There are difficulties in assessing adherence and
      developing interventions. The majority of both qualitative and quantitative
      studies indicate that a collaborative approach when patients are involved in the
      decision-making process appear to be the most effective. The focus on trial
      driven, specialty-specific interventions may not be the most helpful way to
      investigate or improve adherence. This is a fertile area for qualitative work.
      Interventions that focus on the structure of care alongside increasing patient
      involvement in treatment have the most potential to improve adherence and hence
      outcome in mood disorders.

PMID- 16612179
TI  - Self-help Internet interventions for mental disorders.
AB  - PURPOSE OF REVIEW: In recent years a considerable number of publications has
      appeared on various aspects of Internet interventions for mental health care. The
      purpose of the present article is to review the current scientific status of
      Internet interventions for the treatment of mental disorders. RECENT FINDINGS:
      Randomized controlled studies on the use Internet interventions for the treatment
      of mental disorders are still scarce. Most studies in the field have been on
      Internet interventions for the treatment of depressive disorders and anxiety
      disorders, using cognitive behavioural therapy. In addition, a few studies have
      been published on the use of Internet interventions in the treatment of substance
      use disorders (smoking, problem drinking), insomnia and tinnitus. SUMMARY: Recent
      studies provide provisional evidence that Internet interventions may be a
      promising tool for the treatment of some mental disorders.

PMID- 16612180
TI  - Abnormal illness behaviour: physiological, psychological and social dimensions of
      coping with distress.
AB  - PURPOSE OF REVIEW: Pilowsky introduced the term 'abnormal illness behaviour' to
      characterize syndromes of excessive or inadequate response to symptoms, including
      hypochondriasis, somatization, and denial of illness. This review summarizes
      recent work from sociology, health psychology and psychiatry that contributes to
      an understanding of the processes that may underlie abnormal illness behaviour.
      RECENT FINDINGS: Disturbances in the regulation of physiological systems may
      account for many 'unexplained' symptoms and sickness behaviour. Increased
      attention to bodily sensations, sensitivity to pain and catastrophizing play
      important roles in illness behaviour in medical illness. Developmental
      adversities and parental modelling of illness behaviour in childhood may increase
      bodily preoccupation and health care utilization. Apparent cross-national
      differences in illness behaviour may reflect differences in health care systems,
      but cultural models of illness and social stigma remain important determinants of
      illness denial and avoidance of mental health services. SUMMARY: Research into
      illness behaviour is relevant to efforts to rethink the psychiatric nosology of
      somatoform disorders. The discrete somatoform disorders might well be replaced by
      a dimensional framework that identifies specific pathological processes in
      cognition, perception and social behaviour that contribute to bodily distress,
      impaired coping, inappropriate use of health services, chronicity and disability.

PMID- 16612181
TI  - Dissociative and conversion disorders: defining boundaries.
AB  - PURPOSE OF REVIEW: Although dissociative disorders have been described and
      diagnosed for some time, their aetiology, pathogenesis, phenomenology and
      management continues to arouse debate. It is only in recent times that
      researchers have made some progress by integrating trauma related theories with
      more contemporary cognitive theories and neurobiology. RECENT FINDINGS:
      Dissociation as a phenomenon is reported to occur in a variety of disorders. This
      widespread occurrence has contributed to a better understanding of dissociation.
      An expansion of this concept may have contributed to the loss of its original
      significance. Recent studies in the field of dissociation that pertain to its
      aetiology, pathophysiology, neurobiology and management are critically reviewed.
      SUMMARY: Dissociative disorder is conceptually a difficult disorder to study.
      Apart from exposure to trauma, certain primary personality attributes may
      contribute to the propensity to develop dissociative disorder. Recent advances in
      functional neuroimaging facilitated by enhanced knowledge in the neural
      representation of body state have helped to improve our understanding of
      dissociation. There is confusion over the use of various terms such as sexual
      abuse and physical abuse in explaining causality. Current classificatory systems
      have not been found suitable when applied across cultures. In spite of all of
      these limitations, there has been recent progress toward a better understanding
      of dissociative disorders.

PMID- 16612182
TI  - Chronic fatigue syndrome: an update focusing on phenomenology and
      pathophysiology.
AB  - PURPOSE OF REVIEW: Chronic fatigue syndrome is a controversial condition
      especially concerning its clinical definition and aetiopathogenesis. Most recent
      research progress has been made in phenomenology and pathophysiology and we
      focused our review on these two areas. RECENT FINDINGS: The phenomenology
      research supports the notion of a discrete fatigue syndrome which can be
      distinguished from depression and anxiety. The current case definition, however,
      may need an improvement based on empirical data. Recent advances in understanding
      the pathophysiology of chronic fatigue syndrome continue to demonstrate the
      involvement of the central nervous system. Hyperserotonergic state and
      hypoactivity of the hypothalamic-pituitary-adrenal axis constitute other
      findings, but the question of whether these alterations are a cause or
      consequence of chronic fatigue syndrome still remains unanswered. Immune system
      involvement in the pathogenesis seems certain but the findings on the specific
      mechanisms are still inconsistent. Genetic studies provide some evidence of the
      syndrome being a partly genetic condition, but environmental effects seem to be
      still predominant and identification of specific genes is still at a very early
      stage. SUMMARY: The recent findings suggest that further research is needed in
      improving the current case definition; investigating overlaps and boundaries
      among various functional somatic syndromes; answering the question of whether the
      pathophysiologic findings are a cause or consequence; and elucidating the
      involvement of the central nervous system, immune system and genetic factors.

PMID- 16612183
TI  - An update on body dysmorphic disorder.
AB  - PURPOSE OF REVIEW: The present review provides an update on current research into
      body dysmorphic disorder. RECENT FINDINGS: Recent findings can be considered
      under four groupings: the classification of body dysmorphic disorder, its current
      inclusion under the somatoform disorders, and its relationship to obsessive
      compulsive disorder and other obsessive compulsive spectrum disorders; the
      psychotic 'variant' of body dysmorphic disorder, and whether it is simply a more
      severe form of the nonpsychotic type; the cognitive aspects of body dysmorphic
      disorder; and the treatment of body dysmorphic disorder, both in terms of
      pharmacological and psychological parameters. SUMMARY: Body dysmorphic disorder
      does not sit comfortably in the somatoform disorder category, and there is a good
      case for it being considered part of the obsessive compulsive spectrum, although
      it is not merely a subtype of obsessive compulsive disorder. Insight into the
      illness suggests that it represents a spectrum of disorders, and a categorical
      delineation of 'psychotic' and 'nonpsychotic' variants cannot be supported. We
      are beginning to understand more about the neurocognitive aspects of body
      dysmorphic disorder, but more research is required to assess which
      deficits/aberrations (if any) are exclusive to body dysmorphic disorder as an
      entity, and which are a reflection of broader phenomenological manifestations.
      Finally, the mainstay of treatment for body dysmorphic disorder remains
      behaviour/cognitive behaviour therapy and serotonin reuptake inhibitors; much
      more work is required to identify effective interventions for those patients who
      fail to respond to these treatment modalities.

PMID- 16612184
TI  - Anxiety states: a review of conceptual and treatment issues.
AB  - PURPOSE OF REVIEW: The aim is to review studies published between August 2004 and
      July 2005, which address selected conceptual and treatment issues regarding
      various anxiety states. RECENT FINDINGS: It remains unclear whether anxiety
      states are to be better conceptualized as several putatively distinct diagnostic
      entities or as one broadly conceived syndrome within which there are no clear
      boundaries between various manifestations of anxiety. The efficacy of selective
      serotonin reuptake inhibitors and venlafaxine in the treatment of anxiety states
      has been demonstrated by recent studies, but the comparisons between these agents
      did not show consistent advantages of one over the other. Novel medications for
      anxiety states, especially pregabalin, hold promise, but require further study.
      Cognitive-behavioural therapy for panic disorder is not only efficacious in
      controlled trials, but appears effective in routine clinical settings. A novel
      approach to the combined treatment of anxiety states may involve adding to
      behaviour therapy a medication that enhances associative learning. SUMMARY: There
      is a need for further studies to improve conceptualization and classification of
      anxiety states. Optimal treatment approaches to anxiety states continue to
      involve cognitive-behavioural therapy and pharmacotherapy. Under certain
      circumstances, careful combinations of these basic treatment modalities may
      produce further benefits.

PMID- 16612185
TI  - Deconstructing obsessive-compulsive disorder: a multidimensional perspective.
AB  - PURPOSE OF REVIEW: The aim of this article is to critically summarize the most
      promising attempts to split obsessive-compulsive disorder into subgroups based on
      clinical characteristics (i.e. age of onset, presence of comorbid tics, positive
      family history) and symptom theme, with particular emphasis on the latter. RECENT
      FINDINGS: Attempts to split obsessive-compulsive disorder into mutually exclusive
      sub-groups based on clinical characteristics have been useful but not exempt of
      problems. The complex clinical presentation of the condition can be reduced to a
      few consistent, temporally stable symptom dimensions that can coexist in any
      given individual. Researchers have begun to investigate the genetics and neural
      mechanisms of these symptom dimensions and to develop specific assessment and
      treatment protocols for each particular problem. SUMMARY: The multidimensional
      model of obsessive-compulsive disorder proposes a middle ground between the
      'lumping' and 'splitting' perspectives. The disorder can be better understood as
      a spectrum of multiple potentially overlapping syndromes. The most fruitful
      research strategy will be to examine the common and specific etiological factors
      implicated in each symptom dimension.

PMID- 16612186
TI  - Personality disorders: new data versus old concepts.
AB  - PURPOSE OF REVIEW: The purpose of this paper is to review the most recent
      literature on personality disorders. RECENT FINDINGS: Recent data suggest that
      individual personality disorder criteria and full diagnosis may remit within 1-2
      years. The same line of evidence disputes the separation of axis I and axis II
      disorders and suggests the presence of a continuum. Neuropsychological,
      neurobiological and genetic studies favor the presence of cognitive disorders and
      a non-specific mode of hereditability concerning all externalizing disorders. How
      to best treat personality disorders remains elusive. The most impressive news in
      the forensic field concerns the introduction of a new concept, dangerous and
      severe personality disorder by the UK government, for prevention and treatment
      purposes. SUMMARY: The most recent data do not adequately support a separate axis
      II. Future classification may need to move personality disorders to axis I, each
      under a suitable group of diseases and eliminate the very term 'personality' from
      the nomenclature, since it constitutes an empirically unsupported theoretical
      invasion in a system supposed to be 'atheoretical'.

PMID- 16612187
TI  - Suicide and deliberate self-harm in personality disorders.
AB  - PURPOSE OF REVIEW: This article reviews literature published over the period
      January 2004-May 2005 on suicidal behaviour and self-harm in personality
      disorders. RECENT FINDINGS: Studies have confirmed that personality disorders and
      their co-morbidity with other psychiatric conditions are risk factors for both
      fatal and nonfatal suicidal behaviours, and self-mutilation. Negative life
      events, childhood sexual abuse, difficulties in social functioning, deficits in
      future-directed thinking and time perception, as well as familial and
      neurocognitive factors may be related to increased suicide risk in individuals
      with borderline and other personality disorders. Findings seem to confirm that
      suicidality and self-injurious behaviour are efficient DSM-IV diagnostic criteria
      for borderline personality disorder. Out of several psychosocial and
      pharmacological interventions for treating suicidality in personality disorders,
      only one randomized, controlled study has recently been published. Medico-legal
      concerns related to the clinical management of chronically suicidal patients,
      including hospitalization and alternative treatment approaches, are also
      discussed. SUMMARY: Although recent studies have contributed to the theoretical
      knowledge and clinical practice, there are unsettled questions that should be
      addressed in the future. More randomized, controlled trials evaluating the
      efficacy of interventions in suicidal individuals with personality disorders
      should be conducted. As the majority of studies conducted to date have
      concentrated on borderline personality disorder and antisocial personality
      disorder, the prevalence and risk factors for suicidal behaviours and self
      mutilation in other personality disorders require further clarification. The
      introduction of unified nomenclature related to suicidal behaviours and self
      mutilation would facilitate comparability of results across studies.

PMID- 16612188
TI  - Bibliography. Current world literature. Mood disorders.

PMID- 16612191
TI  - Treatment of schizophrenia patients: comparing new-generation antipsychotics to
      each other.
AB  - PURPOSE OF REVIEW: Although the debate on whether new antipsychotics have
      advantages over the old neuroleptics has recently been refueled by the first
      publication of the Clinical Antipsychotic Trials of Intervention Effectiveness
      results, one of the new challenges in the pharmacological management of
      schizophrenia patients is to choose among the new-generation drugs. RECENT
      FINDINGS: Earlier work has compared these medications primarily to traditional
      antipsychotics and until very recently there was little published information on
      the relative efficacy/safety of new-generation antipsychotics. SUMMARY: This
      review covers studies wherein therapeutic effects and adverse events of these
      drugs in schizophrenia patients were compared in head-to-head studies and that
      were published in 2005. Information is clearly more homogenous on the safety
      profile side, while the available evidence still offers little help for the
      clinicians' daily struggles to find the optimally effective antipsychotic for an
      individual schizophrenia patient.

PMID- 16612192
TI  - What have we learned from proton magnetic resonance spectroscopy about
      schizophrenia? A critical update.
AB  - PURPOSE OF REVIEW: This review discusses recent studies investigating
      schizophrenia with proton magnetic resonance spectroscopy including the first
      meta-analysis [Steen RG, Hamer RM, Lieberman JA. Measurement of brain metabolites
      by 1H magnetic resonance spectroscopy in patients with schizophrenia: a
      systematic review and meta-analysis. Neuropsychology 2005; 30:1949-1962]. We also
      highlight methodological issues and suggest a modality for future research to
      further explore glutamatergic dysfunction in schizophrenia. RECENT FINDINGS:
      Despite methodological differences, spectroscopy studies with schizophrenia show
      reductions in N-acetylaspartate in the medial temporal and prefrontal regions.
      Other areas such as the anterior cingulate, parietal cortex thalamus, and
      cerebellum may also have N-acetylaspartate reductions. The proton magnetic
      resonance spectroscopy studies at higher fields and with shorter echo time have
      revealed abnormalities in glutamate and glutamine. Animal studies have shown that
      the discrepancies in metabolites between patients and controls are not due to
      antipsychotic medication exposure, and that chronic exposure to N-methyl-D
      aspartate antagonists has produced decreased N-acetylaspartate in the temporal
      cortex. The human and animal studies both support an excitoxic glutamatergically
      mediated process that may explain decreased N-acetylaspartate, volume loss, and
      the poor outcomes of schizophrenia. SUMMARY: Use of higher field strengths and
      longitudinal studies may reveal a progressive excitoxic glutamatergic process
      that leads to N-acetylaspartate and volume reductions. This may lead to the
      development of neuroprotective agents that change the course of schizophrenia.

PMID- 16612193
TI  - Social outcomes in schizophrenia: from description to action.
AB  - PURPOSE OF REVIEW: The reality of schizophrenia is not fully expressed by
      measures of psychopathology and both descriptive research and research into
      interventions benefit from the investigation of social outcomes. We define these
      as measures which reflect performance compared to normal social expectations,
      either of oneself or of another. The studies we reviewed looked at the effects on
      summary measures, for example, quality of life, as well as simpler, more self
      explanatory outcomes such as employment, marital status, financial independence
      and housing. RECENT FINDINGS: The review contrasts studies which describe the
      determinants of social outcomes and studies designed to estimate the effects of
      interventions on these outcomes. Recent descriptive studies demonstrate that
      social outcomes have both longitudinal and cross-sectional associations with
      cognitive impairment, preexisting functional impairment and certain symptoms.
      Studies of both pharmacological and social interventions suggest that, at best,
      these can affect social outcomes. SUMMARY: Simpler social outcomes are reported
      less frequently than summary measures which can make interpretation more
      difficult, thus diluting a potential advantage of social outcome measures to
      researchers and clinicians alike. Social outcomes are underreported compared to
      measures of psychopathology, particularly in trials of interventions.

PMID- 16612194
TI  - Effects of antipsychotics on brain structure.
AB  - PURPOSE OF REVIEW: This review highlights the recent findings of different
      effects of typical and atypical antipsychotics on brain structure. RECENT
      FINDINGS: Studies examining the effect of treatment with typical antipsychotics
      on brain structure revealed a significant increase in basal ganglia volumes and
      decreased grey matter volume in different cortical regions. These volume changes
      were detectable even after a 12-week treatment. In contrast to these results,
      treatment with atypical antipsychotics does not seem to change basal ganglia
      volumes in neuroleptic-naive patients. Moreover, switching from typical to
      atypical antipsychotic treatment reduces the increased basal ganglia volume to
      normal values compared with healthy controls. Only the volumes of thalamus and
      cortical grey matter increased after atypical antipsychotic treatment. SUMMARY:
      Currently, there is growing evidence that atypical antipsychotics might
      ameliorate structural changes caused by the disease process underlying
      schizophrenia and effects of typical antipsychotics. Further studies have to
      investigate the mechanism leading to these varying effects on brain structure.

PMID- 16612195
TI  - Is the glycine site half saturated or half unsaturated? Effects of glutamatergic
      drugs in schizophrenia patients.
AB  - PURPOSE OF REVIEW: Current treatments for schizophrenia target the dopamine
      system. Developments of new treatments that target the glutamate system, however,
      are under progress, in particular, for the N-methyl-D-aspartate-type glutamate
      receptor. Compared with dopaminergic treatments, these treatments may show
      improved efficacy in the treatment of persistent negative symptoms. RECENT
      FINDINGS: During the past year, clinical trials have been published with several
      agonists at the glycine site of the N-methyl-D-aspartate receptor, including
      glycine, D-serine, D-alanine and with the glycine transport inhibitor, sarcosine.
      Studies published during the past year indicate highly significant beneficial
      effects on negative symptoms when these compounds are added to both conventional
      and newer atypical antipsychotics in efficacy models although an effectiveness
      trial of current formulations of glycine and D-cycloserine failed to show an
      overall benefit. Relevant issues across studies may include the compound chosen,
      its formulation and tolerability, populations studied, and the nature and dose of
      the base antipsychotic treatment. SUMMARY: The present findings continue to
      support the use of N-methyl-D-aspartate/glycine site agonists as potential new
      treatments for persistent negative symptoms of schizophrenia. Ongoing work with
      novel compounds and new formulations may assist in the translation of these
      advances into clinic-ready pharmacotherapies.

PMID- 16612196
TI  - An update on the genetics of schizophrenia.
AB  - PURPOSE OF REVIEW: This paper reviews recent molecular genetic studies of
      schizophrenia and evaluates claims implicating specific genes as susceptibility
      loci. RECENT FINDINGS: Molecular genetic studies have identified several
      potential regions of linkage and two associated chromosomal abnormalities, and
      the evidence is accumulating in favour of several positional candidate genes.
      Currently, the strongest evidence for putative schizophrenia susceptibility loci
      relates to the genes encoding dysbindin (DTNBP1) and neuregulin (NRG1). For other
      genes, disrupted in schizophrenia (DISC1), D-amino acid oxidase activator (DAOA),
      regulator of G-protein signalling 4 (RGS4) and V-AKT murine thymoma viral
      oncogene homolog 1 (AKT1) the data are promising but not yet compelling. In the
      most convincing cases, the risk haplotypes appear to be associated with small
      effect sizes and do not fully explain the linkage findings that prompted each
      study. SUMMARY: The ability of positional genetics to implicate novel genes and
      pathways will open up new vistas for neurobiological research. Despite the
      accumulation of significant genetic data, however, the susceptibility variants
      have yet to be identified and detailed follow-up studies are now required.

PMID- 16612197
TI  - Schizophrenia and bipolar disorder: differences and overlaps.
AB  - PURPOSE OF REVIEW: Following the recent progress mainly in the fields of genetics
      and neurobiology, the validity of the diagnostic distinction between
      schizophrenia and bipolar disorder is increasingly challenged. RECENT FINDINGS:
      Evidence for basic neurobiological processes common for both disorders is
      expanding with regard to (a) susceptibility genes, (b) neurodevelopment (for
      example myelination), and (c) brain functions (for example sensory gating,
      visuospatial achievement). Recent epidemiological studies also stress
      communalities. SUMMARY: The diagnostic split between schizophrenia and bipolar
      disorder is unable to define distinct etiological and/or pathophysiological
      entities.

PMID- 16612198
TI  - Mass hysteria revisited.
AB  - PURPOSE OF REVIEW: Instances of mass psychogenic response have occurred
      throughout history, and across population groups; however, the present-day threat
      of terrorism and biological warfare is expected to enhance societal vulnerability
      to epidemics of such events. This paper provides a brief review of the current
      state of knowledge regarding the conceptualization, diagnosis, and management of
      mass psychogenic response. RECENT FINDINGS: Various terms are nowadays used to
      denote mass hysteria, such as 'mass psychogenic illness' and 'mass sociogenic
      illness'. Recent studies investigating personality types predisposed to mass
      hysteric reactions are inconclusive with a range of results found. Cognitive
      models of this condition have been effective in promoting empowerment and
      adaptation among vulnerable individuals. The actions of governments, medical
      communities, and the media are pivotal in the management of mass hysteria.
      SUMMARY: The diagnosis of mass hysteria remains contentious, and the mechanisms
      underlying its perpetuation are similarly ambiguous. The prevalence of 'threat'
      within the modern sociocultural climate is likely to increase the incidence of
      the condition, and this could result in serious implications for health services.
      A holistic approach entailing the collaboration of various public sectors
      performing a range of preventive activities will be required to contain future
      mass psychogenic reactions.

PMID- 16612199
TI  - Diamonds in the coalface: new research in consultation-liaison psychiatry.
AB  - PURPOSE OF REVIEW: Consultation-liaison psychiatry deals with patients who
      manifest both psychological and somatic symptoms and involves a close and
      collaborative interaction with other medical specialities. While it is a
      clinically rich area, resource constraints and service requirements have meant
      that it has perhaps contributed a little below its weight in academic terms. This
      review, although far from exhaustive, seeks to present some themes of recent
      research in this fascinating discipline. RECENT FINDINGS: The need to demonstrate
      the utility, and ensure the funding, of a service that is all too often regarded
      as 'non-core' by both mental health services and general hospitals remains
      constant. Useful work is being done in streamlining data collection, accurately
      measuring disability and improving outcomes for these complex and resource
      intensive patients. Recent reviews have helped to clarify our understanding of
      medication-induced depression, the treatment options in self-harm, the place of
      psychosocial interventions in oncology, and the relationship between depression
      and heart disease among other areas. SUMMARY: Consultation-liaison psychiatry is
      a fascinating and underresearched field. Important work remains to be done in
      service delivery, diagnosis, treatment and outcome, as well as medical ethics and
      systems research. Although our knowledge is progressing, many existing studies
      are underpowered and multisite collaborations are necessary. Our patients carry
      an enormous burden of ill health and require the services of skilled clinicians,
      advocates and treatment brokers.

PMID- 16612200
TI  - Recent trends in behavioral medicine.
AB  - PURPOSE OF REVIEW: Behavioral medicine is an interdisciplinary field, integrating
      research from a variety of disciplines. This review focuses on recent advances
      and developments in behavioral medicine. RECENT FINDINGS: Stress, as well as
      having a role in the etiology and maintenance of somatic disease and somatoform
      disorders, is an important factor in the behavioral medicine literature.
      Consequentially, recent advances in psychological interventions targeting these
      conditions were developed. Furthermore, a variety of psychobiological mechanistic
      studies investigating the dysregulations of stress axes in conditions relevant to
      behavioral medicine have been undertaken. SUMMARY: Studies investigating factors
      and processes relevant to health and illness clearly demonstrate the impact of
      psychosocial factors such as stress. The biopsychosocial perspective becomes
      increasingly sophisticated, focusing on specific disease processes and
      empirically tested and effective interventions.

PMID- 16612201
TI  - Stressful life events and physical health.
AB  - PURPOSE OF REVIEW: This review summarizes the findings of recent researches from
      selected empirical and nonempirical publications focused on stressful life events
      and physical health. RECENT FINDINGS: The findings can be divided into
      biological, psychological, and social issues concerning the important
      relationship between stressful life events and physical health. Growing evidence
      in the field of psychoneuroimmunology contributes to the understanding of the
      mechanisms by which stressful events affect physical health. The interactions
      between behavior, central nervous system, and endocrine system that might cause
      immunosuppression is the most fascinating finding in modern medicine, and its
      implications are important for the prevention and treatment of somatic illnesses.
      Trauma, abuse, and stressful events have been studied extensively, especially
      among vulnerable groups such as children, women, caregivers, and combatants. Risk
      factors and resilience were the focus of attention of some authors as well as the
      behavioral intervention for coping with stressful events. SUMMARY: The findings
      support old observations and case reports of a close link between stressful life
      events and physical health and emphasize the necessity of early recognition and
      timely management of stress-induced illnesses. Psychosomatic approach,
      multidimensional diagnostics, and treatment should be sine qua non in the
      integrated care of affected people and should improve their quality of life.

PMID- 16612202
TI  - Physical activity and cognition in old age.
AB  - PURPOSE OF REVIEW: With the rapid ageing of the world's population, investigating
      protective factors that may prevent or delay age-related disorders has become a
      new public health priority. Dementia is a common age-related disorder, affecting
      up to one in every two people reaching 80 years of age or above. Amongst the
      various potential 'protective factors' currently under investigation, physical
      activity seems to hold promise for the primary and the secondary prevention of
      dementia. This paper critically reviews the evidence in support of the
      association between exercise and cognitive decline/dementia, as reported by
      cohort studies or clinical trials. RECENT FINDINGS: The results of cohort studies
      show that physical activity is associated with better cognitive function and less
      cognitive decline in later life although there is only scant evidence suggesting
      that physical activity may in fact reduce the risk of dementia and Alzheimer's
      disease. In addition, data to support the systematic introduction of physical
      activity programmes to reduce the risk of dementia in later life are not as yet
      available from randomized clinical trials. SUMMARY: The results of observational
      studies are largely consistent with the hypothesis that physical activity reduces
      the risk of cognitive decline and dementia in later life. These findings are,
      however, not as yet adequately supported by data from randomized clinical trials.

PMID- 16612203
TI  - General medical and psychiatric perspectives on somatoform disorders: separated
      by an uncommon language.
AB  - PURPOSE OF REVIEW: While Diagnostic and Statistical Manual of Mental Disorders-IV
      provided updated definitions and diagnostic criteria for the diagnoses subsumed
      under the category of somatoform disorders, various nosological questions are
      still unresolved. We assessed current research activity on important key concepts
      related to nosology, validity, and reliability of the Diagnostic and Statistical
      Manual of Mental Disorders-IV somatoform diagnoses. RECENT FINDINGS: The initial
      Medline search for articles from 2000 through 2005 yielded a total of 912
      articles. After checking for redundancy and excluding publications using other
      than Diagnostic and Statistical Manual of Mental Disorders-IV diagnostic
      criteria, a total of 101 articles was further reviewed. Heterogeneity of papers
      precluded statistical approaches; thus, a descriptive and narrative review was
      pursued. SUMMARY: It appears that applying the specific categories and criteria
      as proposed by Diagnostic and Statistical Manual of Mental Disorders-IV only
      captures a small proportion of the phenomena of interest at the interface of
      medicine and psychiatry. A paradigm shift towards 'general medical/psychiatry
      interface disorders' in exchange for the current dichotomy of 'mind' vs. 'body'
      disorders, may reduce stigma associated with current diagnostic labeling, improve
      user acceptability, and stimulate research in this important but still fragmented
      clinical area that still lacks agreed-upon diagnostic definitions.

PMID- 16612204
TI  - Psychosomatic disorders in developing countries: current issues and future
      challenges.
AB  - PURPOSE OF REVIEW: This paper focuses on understanding of the concept, recent
      advances, and challenges to be faced in the field of psychosomatic disorders by
      the developing countries. RECENT FINDINGS: Changing health scenario in developing
      countries has led to imminent epidemic of noncommunicable diseases along with the
      unmet agenda of controlling infectious diseases. Psychosomatic medicine has a
      role to play in curtailing the upcoming epidemic. Research studies on
      psychosomatic disorders from developing countries are very few. Most of the
      publications are in nonpsychiatric medical journals covering explorative to
      intervention studies. Traditional, complementary, and alternative medicines such
      as ayurveda are already playing their role in the area of psychosomatic disorders
      in developing countries. SUMMARY: The role and responsibility of the psychiatrist
      is changing from treating major mental disorders to preventing and treating
      psychosomatic disorders. In this regard, developing countries have to meet
      various challenges such as development of manpower, training of medical and
      paramedical staff, funding resources for clinical practice and research,
      coordinating with complementary and alternative medicines, and networking with
      policy makers in combating the imminent epidemic.

PMID- 16612205
TI  - Bibliography. Current world literature. Schizophrenia.

PMID- 16612207
TI  - The cannabis withdrawal syndrome.
AB  - PURPOSE OF REVIEW: The demand for treatment for cannabis dependence has grown
      dramatically. The majority of the people who enter the treatment have difficulty
      in achieving and maintaining abstinence from cannabis. Understanding the impact
      of cannabis withdrawal syndrome on quit attempts is of obvious importance.
      Cannabis, however, has long been considered a 'soft' drug, and many continue to
      question whether one can truly become dependent on cannabis. Skepticism is
      typically focused on whether cannabis use can result in 'physiological'
      dependence or withdrawal, and whether withdrawal is of clinical importance.
      RECENT FINDINGS: The neurobiological basis for cannabis withdrawal has been
      established via discovery of an endogenous cannabinoid system, identification of
      cannabinoid receptors, and demonstrations of precipitated withdrawal with
      cannabinoid receptor antagonists. Laboratory studies have established the
      reliability, validity, and time course of a cannabis withdrawal syndrome and have
      begun to explore the effect of various medications on such withdrawal. Reports
      from clinical samples indicate that the syndrome is common among treatment
      seekers. SUMMARY: A clinically important withdrawal syndrome associated with
      cannabis dependence has been established. Additional research must determine how
      cannabis withdrawal affects cessation attempts and the best way to treat its
      symptoms.

PMID- 16612208
TI  - Psychosis among substance users.
AB  - PURPOSE OF REVIEW: This work reviews the evidence that substances of abuse can
      cause psychosis in nonpsychotic persons. The review is based on the concept that
      psychosis exists in continuum. Studies examining substance use in, or its effect
      on, already psychotic individuals were not reviewed. RECENT FINDINGS: A
      substantial proportion of substance users experience psychosis. Use of cocaine,
      amphetamines, cannabis and alcohol seems to be associated with greater risk for
      psychosis. Severity and duration of use, age at the time of first use and
      vulnerability to develop psychosis by virtue of familial, possibly genetic and
      personality factors seem to be the determinants for the development of psychosis.
      Epidemiological and preliminary biological studies suggest that cannabis is a
      component cause in the development of schizophrenia. Evidence for the causative
      role of other substances is less systematic. SUMMARY: There exists strong
      evidence that abuse of substances is associated with greater risk for psychosis
      and preliminary evidence for their causative role in the development of
      psychosis. More systematic examination of this issue is likely to throw light on
      the neurobiology of psychosis and possibly help the vulnerable population in
      primary prevention.

PMID- 16612209
TI  - Insights from recent positron emission tomographic studies of drug abuse and
      dependence.
AB  - PURPOSE OF REVIEW: Recent positron emission tomographic studies demonstrate a
      variety of abnormalities in the brains of addicted individuals. This review aims
      to discuss and highlight these findings. RECENT FINDINGS: The recent findings are
      as follows: (a) the reward response to an addictive substance is associated with
      increased dopamine release in the striatum. (b) Activation of the orbitofrontal
      region is involved in the reinforcing properties of a drug. (c) Behavioral,
      cognitive and affective abnormalities are associated with alterations in specific
      brain networks and regions (e.g., prefrontal cortices) in drug abusers. (d)
      Personality traits may play a role in the susceptibility to addiction and the
      brain's responses to drugs. (e) Sex-differences exist for cue-induced craving.
      (f) Several studies have confirmed decreased D2 receptors in drug users, which is
      associated with increased salience to drug cues. (g) Serotonergic transporters
      are decreased in the current users of 3,4-methylene-deoxy-methamphetamine but
      found normal in the past users of 3,4-methylene-deoxy-methamphetamine. SUMMARY:
      Abnormalities in the dopaminergic, opioid, and serotonergic systems in drug
      abusers are seen in positron emission tomography scans. Decreased D2 receptor
      densities in drug users, whether premorbid or the consequence of substance
      misuse, imply a source of the susceptibility to relapse of this population.
      Insights from these studies could lead to better treatment approaches targeting
      specific neurotransmitter systems.

PMID- 16612210
TI  - New findings on the genetic influences on alcohol use and dependence.
AB  - PURPOSE OF REVIEW: Alcohol dependence is a complex disorder with a well
      documented highly hereditary nature. This article reviews the recent advances in
      our understanding of the direct and indirect genetic influences on alcohol use
      and dependence. RECENT FINDINGS: Recent findings can be summarized as follows:
      (a) twin studies have defined and estimated the risks of general and specific
      alcohol-related vulnerabilities. (b) Linkage studies have provided largely
      inconsistent findings, though several chromosomal regions have been implicated.
      (c) Quantitative trait loci analyses in animals have identified that the Mpdz
      gene predisposes to alcohol dependence and withdrawal. (d) Examination of family
      based samples has identified several genes including GABRA2 and CHRM2 thought to
      be associated with alcohol dependence. SUMMARY: Despite great advances in
      understanding of genetic vulnerability in alcohol use disorders, only two gene
      complexes, ADH and ALDH2, have been identified as having defined effects on
      alcohol use and liability to dependence in humans. New genes associated with
      increased risks for the disorder will certainly be added to this list in the near
      future. Neurobiological analyses of the effects of these genes will surely
      contribute to further understanding of the cause of alcohol dependence and the
      interindividual differences in risks.

PMID- 16612211
TI  - The place of detoxification in treatment of opioid dependence.
AB  - PURPOSE OF REVIEW: This review summarizes current research on the management of
      opioid withdrawal and considers the selection of the approach in different
      situations. RECENT FINDINGS: The recent publication of three controlled trials
      makes firm conclusions about the relative effectiveness of newer approaches
      (antagonist-induced withdrawal under anaesthesia or with minimal sedation;
      buprenorphine) to the management of opioid withdrawal possible. SUMMARY:
      Antagonist-induced withdrawal under anaesthesia should not be pursued as it has
      an increased risk of life-threatening adverse events and has no additional
      benefits relative to antagonist-induced withdrawal under minimal sedation.
      Antagonist-induced withdrawal with minimal sedation is feasible and may be
      suitable for those who intend to enter antagonist-maintenance treatment with a
      clear commitment to abstinence and good support. Buprenorphine is suitable for
      quick withdrawal, supports transition to naltrexone maintenance treatment, is
      safe and effective in outpatient settings and can be extended into maintenance
      treatment if the detoxification attempt is unsuccessful. Adrenergic agonists
      (clonidine and lofexidine) remain an effective option for those who do not want
      to use an opioid and do not intend to transfer to naltrexone maintenance
      treatment, with lofexidine being preferable for outpatient settings. Through
      appropriate choice of approach, detoxification can be a gateway to multiple, long
      term treatment options.

PMID- 16612212
TI  - Family interventions for drug and alcohol misuse: is there a best practice?
AB  - PURPOSE OF REVIEW: Recent developments in research and practice have highlighted
      the effectiveness of family interventions in substance misuse treatment. The
      present paper will critically review studies of family approaches published over
      the past 12 months, assess the current state of this field and suggest future
      directions. RECENT FINDINGS: Family interventions lead to positive outcomes for
      both misusers and family members. Some recent interventions have widened the
      focus also to include other members of the user's social networks and have
      focused on a range of treatment goals. SUMMARY: An increasingly robust evidence
      base supports family-focused and social network-focused interventions in
      substance misuse treatment. Recent studies have continued to show that family and
      network approaches either match or improve outcomes when compared with individual
      interventions. Research needs (and is starting) to consider a broader set of
      outcomes relevant to family and network interventions, besides simply making an
      impact on substance use. The major challenge involves implementation of family
      approaches in routine service provision; interventions with most evidence
      supporting them are not used routinely in practice. Research studies and policy
      initiatives need to focus on dissemination of family approaches and their
      integration into treatment services.

PMID- 16612213
TI  - Cognitive deficits in the families of patients with schizophrenia.
AB  - PURPOSE OF REVIEW: Studies of first-degree relatives of patients with
      schizophrenia over the past 25 years have reported a number of cognitive
      deficits, primarily in the domains of memory and executive function.
      Nevertheless, due to a number of methodological issues, such as including
      different types of relatives and not controlling for possible psychopathology, it
      is not yet clear that these findings can fully support a conclusion of
      heritability of cognitive dysfunction associated with a schizophrenia genotype.
      RECENT FINDINGS: Several recent meta-analyses have shown that the most consistent
      deficit shown by relatives is impaired performance on 'maintenance plus' frontal
      lobe tasks requiring increased effort and higher central executive processing.
      Studies of multiplex families (multiple diagnoses in one family) also report that
      family members tend to have more difficulty on executive function tasks. Another
      interesting trend is research on subgroups of patients and relatives displaying
      distinct cognitive syndromes, particularly a subgroup with a generalized
      cognitive deficit. SUMMARY: As methodological designs improve, this field of
      study holds promise not only for understanding the neurobiological mechanisms of
      schizophrenia and the associated cognitive deficits, but also for possibly
      describing endophenotypes that may lead to identifying at-risk patients and
      relatives.

PMID- 16612215
TI  - Sleep and youth suicidal behavior: a neglected field.
AB  - PURPOSE OF REVIEW: Sleep undergoes substantial changes during adolescence and
      suicide risk begins to increase during this period as well. This review focuses
      on recent literature on the relationship between sleep and suicidal behavior and
      proposes directions for future research. RECENT FINDINGS: Adolescent sleep is
      characterized by widespread sleep restriction, irregular sleep schedules, daytime
      sleepiness, and elevated risk for sleep disturbances. More research on adolescent
      sleep and psychosocial impairment, psychiatric disorders, and suicidal behavior
      has been conducted. Suicidal psychiatric patients had more sleep disturbances
      including insomnia, hypersomnia, or nightmares than nonsuicidal patients. Shorter
      rapid eye movement latency and increased rapid eye movement activity have been
      noted to be a marker of suicidality in psychiatric patients. Epidemiological
      studies have demonstrated that insomnia, nightmares, and sleep insufficiency are
      associated with elevated risk for suicide. Although the link between insomnia and
      suicidal behavior appears to be mediated by depression, existing data suggest an
      independent predictive role of nightmares in future suicidal behavior. SUMMARY:
      Sleep loss or disturbances are likely to signal an increased risk of future
      suicidal action in adolescents. Large-scale prospective studies and
      neurobiological studies are needed for a better understanding of the complex
      relationship between sleep, psychopathology, and youth suicidal behavior.

PMID- 16612214
TI  - Understanding sleep-wake behavior and sleep disorders in children: the value of a
      model.
AB  - PURPOSE OF REVIEW: Sleep-wake problems such as night wakings, excessive crying,
      or difficulties in falling asleep are frequent behavioral issues during
      childhood. Maturational changes in sleep and circadian regulation likely
      contribute to the development and maintenance of such problems. This review
      highlights the recent research examining bioregulatory sleep mechanisms during
      development and provides a model for predicting sleep-wake behavior in young
      humans. RECENT FINDINGS: Findings demonstrate that circadian and sleep
      homeostatic processes exhibit maturational changes during the first two decades
      of life. The developing interaction of both processes may be a key determinant of
      sleep-wake and crying behavior in infancy. Evidence shows that the dynamics of
      sleep homeostatic processes slow down in the course of childhood (i.e., sleep
      pressure accumulates more slowly with increasing age) enabling children to be
      awake for consolidated periods during the day. Another current topic is the
      adolescent sleep phase delay, which appears to be driven primarily by
      maturational changes in sleep homeostatic and circadian processes. SUMMARY: The
      two-process model of sleep regulation is a valuable framework for understanding
      and predicting sleep-wake behavior in young humans. Such knowledge is important
      for improving anticipatory guidance, parental education, and patient care, as
      well as for developing appropriate social policies.

PMID- 16612216
TI  - Depression in neurological disorders: an update.
AB  - PURPOSE OF REVIEW: Depressions are a heterogeneous group of conditions that
      contribute significantly to impairments in quality of life, independent of the
      severity of neurological illness. Depression may predate neurological signs and
      symptoms in the evolution of neurodegenerative disorders, and there is some
      evidence that depressive illness itself may be a risk factor in the aetiology of
      some dementias. This review aims to summarize the relevant current literature on
      diagnosis, aetiology and treatment of depression in neurology. RECENT FINDINGS:
      Diagnosing depression in neurological conditions can be particularly difficult
      because of communication difficulties and changes in emotional expression as a
      result of the underlying neurological disease. Rating scales loaded towards
      somatic symptoms can show poor validity for screening or rating of severity in
      this setting. The evidence for the treatment of depression in neurological
      disease is scant, and often the treatment advice is based on consensus views of
      clinicians. Nevertheless, there have been some clinical trials, which are
      reported. SUMMARY: Depression is common in neurology. It is underrecognized and
      undertreated. Recent research has allowed us to define depression more clearly in
      this setting. Trials of treatment are urgently needed, especially as depression
      is a significant factor in quality of life and may affect prognosis.

PMID- 16612217
TI  - Functional magnetic resonance imaging of cholinergic modulation in mild cognitive
      impairment.
AB  - PURPOSE OF REVIEW: Mild cognitive impairment often represents the earliest
      clinical phase of Alzheimer's disease and is thought to involve synaptic
      dysfunction. Functional neuroimaging methods may be sensitive to these early
      physiologic changes and may be useful in early detection, therapeutic monitoring,
      and prediction of treatment response and other clinical outcomes. This review
      will focus on functional magnetic resonance imaging and its use in measuring the
      effects of cholinergic modulation in mild cognitive impairment. RECENT FINDINGS:
      Functional magnetic resonance imaging has begun to be applied to measure changes
      in regional brain activation during cognitive task performance after
      pharmacologic manipulation. In mild cognitive impairment, recent reports have
      appeared demonstrating alterations in neocortical activation after acute and
      prolonged administration of acetylcholinesterase inhibitors. These functional
      changes may relate to both behavioral performance and measures of brain structure
      (e.g., hippocampal volume). SUMMARY: Pharmacologic functional magnetic resonance
      imaging is a rapidly emerging field, with applications in both basic human
      neuroscience and clinical psychiatry and neurology. Its use in mild cognitive
      impairment and Alzheimer's disease may provide novel insights into the
      cholinergic system, memory, and neurodegenerative disease.

PMID- 16612218
TI  - Apoptosis in schizophrenia: pathophysiologic and therapeutic considerations.
AB  - PURPOSE OF REVIEW: A role for apoptosis in schizophrenia has long been
      hypothesized, but only recently have studies begun to examine this issue. This
      paper will review studies of apoptotic regulatory proteins, DNA fragmentation,
      and gene microarrays to highlight the potential role of apoptosis in the
      pathophysiology and treatment of schizophrenia. RECENT FINDINGS: Although several
      studies indicate a possible increase in apoptotic susceptibility, accumulating
      evidence suggests that apoptotic activity may actually be downregulated in
      chronic schizophrenia. Furthermore, antipsychotics produce complex effects on
      apoptotic regulation in the central nervous system, activating both proapoptotic
      and antiapoptotic signaling pathways. SUMMARY: Somewhat paradoxically, apoptosis
      appears to be downregulated in cortex of patients with chronic schizophrenia.
      This could reflect either a pathophysiological failure to mount an effective
      response to an apoptotic insult or an appropriate compensatory response to an
      earlier insult. The former could account for evidence indicating reduced neuronal
      viability without large-scale neuronal death in schizophrenia. The latter could
      reflect an earlier period of increased apoptotic activity in response to one or
      more proapoptotic insults. Antipsychotic treatment can modify the apoptotic
      response. This suggests implications for treatment, especially if future studies
      indicate that gray matter loss occurs via apoptotic mechanisms.

PMID- 16612219
TI  - The extracellular signal-regulated kinase pathway: an emerging promising target
      for mood stabilizers.
AB  - PURPOSE OF REVIEW: There exists a growing appreciation that, though not classical
      neurodegenerative disorders, severe mood disorders are associated with regional
      impairments of structural plasticity and cellular resilience. Exciting recent
      data suggest that synaptic plasticity probably is involved in mechanisms of
      actions of mood stabilizers and antidepressants. Notably, the extracellular
      signal-regulated kinase pathway is a critical 'plasticity pathway' in the brain.
      The present review summarizes neurobiological, pharmacological, and behavioral
      data on the role of the extracellular signal-regulated kinase pathway in
      regulating some of the symptoms of bipolar disorder and as a therapeutically
      relevant target for mood stabilizers. RECENT FINDINGS: The extracellular signal
      regulated kinase pathway is known to mediate neurotrophic actions and synaptic
      plasticity. Treatment with lithium and valproate activates the extracellular
      signal-regulated kinase pathway in cultured cells and in prefrontal cortex and
      hippocampus. In addition, lithium or valproate treatment promotes neurogenesis,
      neurite growth, and cell survival. The extracellular signal-regulated kinase
      pathway is also targeted by antipsychotics. Modulation of the central nervous
      system extracellular signal-regulated kinase pathway induces animal behavioral
      alterations reminiscent of manic symptoms; these complex behaviors probably
      depend on the effects of extracellular signal-regulated kinase on discrete brain
      regions and the presence of other interacting molecules. SUMMARY: The
      extracellular signal-regulated kinase pathway may represent a novel target for
      the development of improved therapeutics for bipolar disorder.

PMID- 16612220
TI  - Bibliography. Current world literature. Addictive disorders.

PMID- 16612222
TI  - Guideline 1: Minimum technical requirements for performing clinical
      electroencephalography.

PMID- 16612223
TI  - Guideline 2: Minimum technical standards for pediatric electoencephalography.

PMID- 16612224
TI  - Guideline 3: Minimum technical standards for EEG recording in suspected cerebral
      death.

PMID- 16612225
TI  - Guideline 4: Standards of practice in clinical electroencephalography.

PMID- 16612226
TI  - Guideline 5: Guidelines for standard electrode position nomenclature.

PMID- 16612227
TI  - Guideline 6: A proposal for standard montages to be used in clinical EEG.

PMID- 16612228
TI  - Guideline 7: Guidelines for writing EEG reports.

PMID- 16612229
TI  - Guideline 8: Guidelines for recording clinical EEG on digital media.

PMID- 16612230
TI  - Guideline 9A: Guidelines on evoked potentials.

PMID- 16612231
TI  - Guideline 9B: Guidelines on visual evoked potentials.

PMID- 16612232
TI  - Guideline 9C: Guidelines on short-latency auditory evoked potentials.

PMID- 16612233
TI  - Guideline 9D: Guidelines on short-latency somatosensory evoked potentials.

PMID- 16612234
TI  - Guideline 10: Guidelines for writing clinical evoked potential reports.

PMID- 16612235
TI  - Role of leptin in blood pressure regulation and arterial hypertension.
AB  - Leptin is a 16-kDa protein secreted by white adipose tissue that is primarily
      involved in the regulation of food intake and energy expenditure. Plasma leptin
      concentration is proportional to the amount of adipose tissue and is markedly
      increased in obese individuals. Recent studies suggest that leptin is involved in
      cardiovascular complications of obesity, including arterial hypertension. Acutely
      administered leptin has no effect on blood pressure, probably because it
      concomitantly stimulates the sympathetic nervous system and counteracting
      depressor mechanisms such as natriuresis and nitric oxide (NO)-dependent
      vasorelaxation. By contrast, chronic hyperleptinemia increases blood pressure
      because these acute depressor effects are impaired and/or additional sympathetic
      nervous system-independent pressor effects appear, such as oxidative stress, NO
      deficiency, enhanced renal Na reabsorption and overproduction of endothelin.
      Although the cause-effect relationship between leptin and high blood pressure in
      humans has not been demonstrated directly, many clinical studies have shown
      elevated plasma leptin in patients with essential hypertension and a significant
      positive correlation between leptin and blood pressure independent of body
      adiposity both in normotensive and in hypertensive individuals. In addition,
      leptin may contribute to end-organ damage in hypertensive individuals such as
      left ventricular hypertrophy, retinopathy and nephropathy, independent of
      regulating blood pressure. Here, current knowledge about the role of leptin in
      the regulation of blood pressure and in the pathogenesis of arterial hypertension
      is presented.

PMID- 16612236
TI  - Diagnostic certainty in hypertension.

PMID- 16612237
TI  - The burden of hypertension and inadequate control in populations.

PMID- 16612238
TI  - Does blood pressure control require a Cuban-style revolution?

PMID- 16612239
TI  - Assessment of retinal vascular changes in hypertension: new perspectives.

PMID- 16612240
TI  - Sympathetic overdrive as an independent predictor of left ventricular
      hypertrophy: prospective evidence.

PMID- 16612241
TI  - Adducin and microalbuminuria: a complex association.

PMID- 16612242
TI  - Progression of pre-hypertension, stage 1 and 2 hypertension (JNC 7): a population
      based study in Keelung, Taiwan (Keelung Community-based Integrated Screening No.
      9).
AB  - OBJECTIVE: To investigate the prevalence and progression of, and identify risk
      factors for, pre-hypertension, stage 1 and 2 hypertension in a population-based
      study. DESIGN: A prospective cohort study. SETTING: An integrated community-based
      multiple screening program in Keelung, Taiwan. PARTICIPANTS: A total of 67 011
      individuals aged 20-79 years between 1999 and 2003 were included. Of these, 22
      111 re-attended, yielding 53 689 repeated recordings of blood pressure, including
      movement between normal and pre-hypertension and progression from pre
      hypertension to stage 1 or stage 2 hypertension. MAIN OUTCOME MEASURES: Blood
      pressure was defined and classified according to the JNC 7 Report as normal, pre
      hypertension, stage 1, and stage 2 hypertension. RESULTS: Below 50 years of age,
      males had a higher progression rate, particularly from normal to pre
      hypertension, than females. Annual regression rates from pre-hypertension to
      normal were higher in the young age group than in the old age group, particularly
      for females. Factors associated with the occurrence of pre-hypertension were old
      age, male gender, high waist circumference, abnormal blood lipids, smoking,
      chewing betel nuts, lack of exercise, and having parents with hypertension.
      Factors associated with regression from pre-hypertension to normal were body mass
      index, fasting glucose, high-density lipoprotein level, smoking, and parents with
      hypertension. Progression from pre-hypertension to stage 1 hypertension was
      positively related to male gender, higher waist circumference, and having parents
      with hypertension. CONCLUSIONS: The rates of progression and regression of
      hypertension vary with age and gender, anthropometric and biochemical
      measurements, and family history.

PMID- 16612243
TI  - Trends in hypertension care in eastern and south-western Finland during 1982
      2002.
AB  - OBJECTIVE: To assess the trends in blood pressure (BP) levels and the control of
      hypertension in eastern and south-western Finland during 1982-2002. DESIGN: Five
      independent cross-sectional population surveys conducted in 1982, 1987, 1992,
      1997 and 2002. SETTING: The provinces of North Karelia and Kuopio in eastern
      Finland and the region of Turku-Loimaa in south-western Finland. PARTICIPANTS:
      Stratified random samples of men and women aged 25-64 years were selected from
      the national population register. The total number of participants was 29 127.
      MAIN OUTCOME MEASURES: Mean systolic blood pressure (SBP) and diastolic blood
      pressure (DBP), the prevalence and control of hypertension. The distribution of
      all subjects with no antihypertensive drug treatment in 2002 according to the
      modified risk stratification scheme introduced in 2003 European Society of
      Hypertension-European Society of Cardiology guidelines. RESULTS: Mean SBP and DBP
      and the prevalence of hypertension decreased significantly in all areas. The
      proportion of treated hypertensive subjects with adequately controlled BP (SBP <
      140 mmHg and DBP < 90 mmHg) increased from 13.7 to 33.3% in men (P < 0.001) and
      from 11.4 to 32.0% in women (P < 0.001). The unsatisfactory treatment of
      hypertension was mainly a result of the lack of control of high SBP. According to
      the 2003 guidelines, 35.9% of the entire population currently not on
      antihypertensive drug treatment should have been prescribed such treatment within
      a year. CONCLUSIONS: Hypertension care has improved significantly in Finland
      during 1982-2002. However, the difference between the actual situation at the
      population level and the treatment goals presented by the hypertension guidelines
      remains vast.

PMID- 16612244
TI  - Hypertension prevalence, awareness, control and association with metabolic
      abnormalities in the San Marino population: the SMOOTH study.
AB  - BACKGROUND: The aim of the SMOOTH (San Marino Observational Outlooking Trial on
      Hypertension) study was to explore hypertension awareness, treatment and control
      and the associated metabolic abnormalities and risk factors in the population of
      San Marino, a small state in the Mediterranean area, for which limited evidence
      is available. METHODS: Nine general practitioners enrolled 4590 consecutive
      subjects (44% of the San Marino population age 40-75 years), seen in their office
      by collecting history, physical and laboratory data and office blood pressure
      (BP) measurements. RESULTS: Of these subjects, 2446 were normotensive and 2144
      hypertensive; 62.3% of hypertensive patients were aware of their condition, 58.6%
      were treated (monotherapy 31.5%, combination therapy 27.1%), and 21.7% were
      controlled. Hypertension awareness and treatment were more frequent above age 50
      and in females; BP control was similarly low in both genders. As compared to
      normotensives, hypertensive subjects were less frequently smokers (20.1 versus
      27.8%), had greater body mass index (28.1 +/- 4.5 versus 25.8 +/- 3.7 g/m), and a
      higher prevalence of diabetes mellitus (15.8 versus 6.3%), lower high-density
      lipoprotein (HDL) cholesterol and higher prevalence of increased blood total
      cholesterol (66.1 versus 51.3%), triglycerides and serum uric acid. Values of
      subjects with 'high-normal' blood pressure were closer to those of hypertensive
      subjects. The prevalence of metabolic syndrome was higher in hypertensive than in
      normotensive subjects, and in treated than in untreated hypertensives.
      CONCLUSIONS: Even in a small Mediterranean country with high health-care
      standards, hypertension awareness, treatment and control are inadequate and
      hypertension clusters with metabolic abnormalities and risk factors as in non
      Mediterranean areas.

PMID- 16612245
TI  - Success in control of hypertension in a low-resource setting: the Cuban
      experience.
AB  - BACKGROUND: Pharmacologic control of hypertension is an essential component of
      the current strategy to control cardiovascular diseases. Much concern has been
      focused in recent years on the challenge that cardiovascular disease poses for
      developing countries. Available medical therapies should be equally effective in
      low- and high-resource settings; however, this has not yet been demonstrated.
      Cuba has a well-organized primary-care system and has made reduction of
      cardiovascular diseases a priority, particularly through detection and treatment
      of hypertension. METHODS: To determine current hypertension control rates a
      population-based sample of 1667 persons aged 15-74 years was examined in the city
      of Cienfuegos. RESULTS: The prevalence of hypertension, weighted to the age
      structure of the sampled population, was 20%. Among all hypertensives, 78% were
      previously aware of the condition, 61% were currently taking medications, and 40%
      had systolic/diastolic blood pressures < 140/90 mmHg (men = 29%, women = 49%).
      Among treated hypertensives, 62% had blood pressures < 140/90 mmHg. DISCUSSION:
      The level of control documented in this survey is higher than reported previously
      from population surveys in other countries. If confirmed in broader samples in
      Cuba, these findings would suggest that effective control of hypertension is
      highly feasible in low-resource settings.

PMID- 16612246
TI  - Hyperhomocysteinemia predicts total and cardiovascular mortality in high-risk
      women.
AB  - OBJECTIVE: The impact of homocysteine on cardiovascular disease can be more
      detrimental in women than in men, but it is unknown whether this applies to high
      risk women. We therefore investigated the association of hyperhomocysteinemia
      with coronary artery disease (CAD) and cardiovascular mortality in high-risk
      women referred for CAD, both in the total population and in the hypertensive and
      normotensive cohorts. DESIGN: A prospective study cohort. SETTING: A tertiary
      centre. PATIENTS:  INCLUSION CRITERIA: 262 consecutive Caucasian postmenopausal
      women referred for coronary angiography. EXCLUSION CRITERIA: acute myocardial
      infarction and vitamin supplementation. MAIN OUTCOME MEASURE(S): We assessed
      total plasma homocysteine (tHcy), folate levels, and the MTHFR677C-->T
      polymorphism. CAD was defined as a modified Duke Index score greater than 0;
      hyperhomocysteinemia as tHcy levels of 15 micromol/l or greater. The primary
      study outcome was cardiovascular mortality at follow-up. RESULTS: Mild/moderate
      and severe hyperhomocysteinemia was found in 15.1 and 1.6% of women,
      respectively, without differences between CAD and non-CAD women. By the ATPIII
      criteria, 92.2% of the women were in the highest risk class and 55% had CAD;
      however, no association of tHcy with the CAD score was found. After a median
      follow-up of 3.6 years, 23 women (9.1%) had died, 15 (6%) of cardiovascular
      causes. Women with high tHcy levels showed the worst all-cause and cardiovascular
      death-free survival at Kaplan-Meier and Cox regression analysis. Moreover, in the
      hypertensive cohort only women with hyperhomocysteinemia showed increased
      cardiovascular mortality. CONCLUSION: Hyperhomocysteinemia is common in high-risk
      women and adversely affects their prognosis, although it is unrelated to the CAD
      atherosclerotic burden.

PMID- 16612247
TI  - How should patients treated with alpha-blockers be followed? Insights from an
      ambulatory blood pressure monitoring database.
AB  - OBJECTIVE: Adrenergic alpha-antagonists have been suggested to confer lesser
      protection, compared to diuretics, when used as first agents for hypertension.
      While differences in clinic blood pressure may be partly responsible, this
      inferiority is unexpected in light of the metabolic advantages of alpha-blockade.
      The aim of this study was to evaluate the relationship between use of alpha
      blockers and blood pressure dipping. METHODS: A database of a 24-h ambulatory
      monitoring service was cross-sectionally evaluated for associations between
      antihypertensives and dipping. There were 681 treated subjects during a 3-year
      period (age 63 +/- 14, 57% female). RESULTS: Overall, 78 of 681 treated
      hypertensive subjects used alpha-blockers (11%). Nine per cent of dippers and 16%
      of nondippers were treated with alpha-blockade, odds ratio 2.0. Whereas clinic,
      24-h, and awake blood pressures were similar in alpha-blocker users and nonusers,
      sleep blood pressure was significantly higher in the former group. Furthermore,
      significantly fewer subjects given alpha-blockers had a controlled sleep blood
      pressure. Among alpha-blocker nonusers sleep blood pressure was the best
      controlled category, whereas in alpha-blocker users manual blood pressure had the
      highest rate of control. Generally, accounting for covariates of alpha-blockade
      (age, gender, diabetes, total number of medications) did not influence the above
      mentioned trends. Finally, a limited negative dose-response relationship between
      alpha-blockade and dipping magnitude was also noticed. CONCLUSIONS: We found a
      significant negative association between adrenergic alpha-blockade and the
      magnitude of sleep-related blood pressure decline. Awaiting results from
      interventional studies, this may suggest a need to perform ambulatory monitoring
      in patients given alpha-blocking agents (or at least supine and standing
      measurements), and may partially clarify the inferiority of doxazosin in the
      Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial
      (ALLHAT).

PMID- 16612248
TI  - Lack of prognostic role of endothelial dysfunction in subcutaneous small
      resistance arteries of hypertensive patients.
AB  - OBJECTIVE: The presence of endothelial dysfunction in the coronary circulation or
      in the brachial artery has been found to be associated with a greater incidence
      of cardiovascular events. However, no data are presently available about the
      prognostic role of endothelial dysfunction in human small resistance arteries.
      DESIGN AND METHODS: Ninety subjects were included in the present study. They
      were: 10 normotensive subjects, 36 patients with essential hypertension, 10
      patients with phaeochromocytoma, 11 patients with primary aldosteronism, 10
      patients with renovascular hypertension, and 13 normotensive patients with non
      insulin-dependent diabetes mellitus (NIDDM). All subjects were submitted to a
      biopsy of subcutaneous fat from the gluteal or the anterior abdominal region.
      Small resistance arteries were dissected and mounted on an isometric myograph,
      and the concentration-response curves to acetylcholine (from 10 to 10 mol/l)
      (endothelium-dependent vasodilatation) and sodium nitroprusside (from 10 to 10
      mol/l) (endothelium-independent vasodilatation) after precontraction of the
      vessels with norepinephrine were evaluated. The subjects were re-evaluated (by
      clinical visits or telephone interviews) after an average follow-up time of 5.5
      years. RESULTS: Twenty-nine subjects had a documented fatal or non-fatal
      cardiovascular event (5.87%/year). The endothelium-dependent vasodilatation in
      the subcutaneous small arteries was similar in subjects with or without
      cardiovascular events. Also, endothelium-independent vasodilatation to sodium
      nitroprusside was similar in the two groups. Similar results were obtained by
      subdividing patients in the different subgroups (essential hypertension,
      secondary hypertension, etc.). CONCLUSIONS: Our results indicate that endothelial
      dysfunction in the microcirculation does not predict cardiovascular events. It is
      possible that a prognostic role of endothelial dysfunction may be observed when
      other vascular districts prone to atherosclerosis are evaluated, or it might be
      detected only in patients at low to medium cardiovascular risk, in whom
      endothelial dysfunction is less advanced.

PMID- 16612249
TI  - Middle cerebral artery structure and distensibility during developing and
      established phases of hypertension in the spontaneously hypertensive rat.
AB  - OBJECTIVE: The aims of the current study were to examine the structural
      properties of middle cerebral arteries (MCA) from young (5-7 weeks) and adult (20
      24 weeks) spontaneously hypertensive rats (SHR), compared with age-matched Wistar
      Kyoto (WKY) control rats. DESIGN: MCA segments (8-10 per group) were secured onto
      glass pipettes in a small vessel chamber and studied using a pressure
      arteriograph system. Vessels were perfused in Ca2+-free physiological salt
      solution to ensure the absence of tone. The wall thickness and lumen diameter
      were recorded at intraluminal pressures ranging from 3 to 180 mmHg using a video
      dimension analyser. RESULTS: There was a borderline increase in systolic pressure
      of the young SHR, compared with WKY controls, but the systolic pressure of the
      older SHR was significantly raised. The MCA lumen diameter from young SHR was
      reduced across the entire pressure range and arterial distensibility was not
      reduced, compared with WKY vessels. The MCA lumen diameter from adult SHR was
      reduced at high pressure, but converged with the lumen diameter of the WKY
      vessels at 3 mmHg, and the stress-strain relation was shifted to the left,
      compared with the WKY vessels; nevertheless, the slope of the tangential elastic
      modulus-stress relation was not significantly increased. The pressure-wall cross
      sectional area relationship did not differ between strains at either time point.
      CONCLUSIONS: These data demonstrate eutrophic inward remodelling of the MCA from
      young SHR, compared with WKY controls. In the adult SHR the structural changes
      are probably a consequence of a reduced arterial distensibility.

PMID- 16612250
TI  - Exaggerated blood pressure response to exercise is associated with carotid
      atherosclerosis in apparently healthy men.
AB  - OBJECTIVE: Although an exaggerated systolic blood pressure (SBP) response to
      exercise is a predictor of future hypertension and cardiovascular mortality, the
      underlying mechanisms are not fully understood. We tested the hypothesis that an
      exaggerated SBP response is associated with carotid atherosclerosis in a cross
      sectional study of 9073 healthy men (aged 47.8 +/- 8.8 years). METHODS:
      Exaggerated SBP response was defined as an SBP of 210 mmHg or greater during a
      maximal treadmill test. Carotid atherosclerosis was defined as stenosis greater
      than 25% or intima-media thickness greater than 1.2 mm using B-mode
      ultrasonography. RESULTS: An exaggerated SBP response was present in 375 men
      (4.1%). The proportion of individuals with carotid atherosclerosis in the group
      with an exaggerated SBP response to exercise was higher than in the group with a
      normal SBP response (14.4 versus 5.3%, P < 0.001). In a multivariable logistic
      regression model, individuals with an exaggerated SBP (>or= 210 mmHg) response to
      exercise had a 2.02 times [95% confidence interval (CI) 1.33-3.05] increased risk
      of carotid atherosclerosis compared with individuals with an SBP response of less
      than 210 mmHg. The highest quartile (> 61 mmHg) group of relative exercise
      induced increases in SBP showed a 1.57 (95% CI 1.18-2.08) greater risk of carotid
      atherosclerosis compared with individuals in the lowest quartile (< 38 mmHg) in
      the adjusted model. CONCLUSIONS: These results suggest that an exaggerated SBP
      response to exercise is strongly associated with carotid atherosclerosis,
      independent of established risk factors in healthy men. It may be an important
      factor in evaluating hypertension related to target-organ damage.

PMID- 16612251
TI  - Quantification of topological changes in retinal vascular architecture in
      essential and malignant hypertension.
AB  - OBJECTIVE: Grading of hypertension severity by fundoscopic appearance is
      difficult and inaccurate. We investigated whether essential hypertension (EHT)
      and malignant phase hypertension (MHT) were associated with quantifiable
      abnormalities of the topology and architecture of the retinal circulation.
      METHODS: The topology and architecture of the retinal microvasculature were
      compared in images from 20 normotensive subjects, 20 patients with EHT and 20
      patients with MHT. Digitized retinal photographs were analysed by a novel
      multiscale image analysis method using a semi-automated program to quantify
      geometrical and topological properties of arteriolar and venular trees. RESULTS:
      EHT was associated with an increase in the arteriolar length-to-diameter ratio (P
      < 0.01). There were also alterations in arteriolar topology indicative of
      rarefaction, including a marked reduction in the number of terminal branches in
      EHT (P < 0.01). These changes in the arteriolar network were exaggerated in MHT
      and there was also increased venular tortuosity and venular rarefaction in MHT
      compared with normotensive subjects. CONCLUSIONS: Hypertension is associated with
      marked topological alterations in the retinal vasculature, and quantification of
      these changes may be a useful novel approach to the assessment of target organ
      damage in hypertension.

PMID- 16612252
TI  - The chromogranin A fragment catestatin: specificity, potency and mechanism to
      inhibit exocytotic secretion of multiple catecholamine storage vesicle co
      transmitters.
AB  - BACKGROUND: Secretory granules of chromaffin cells and neurons co-store and
      release, by exocytosis, the acidic soluble protein chromogranin A (human, CHGA;
      rodent, Chga) along with catecholamines, neuropeptides and adenosine triphosphate
      (ATP). CHGA serves as a pro-protein and upon proteolytic cleavage it generates
      active peptides, including catestatin (human CHGA352-372), first discovered in
      adrenal medullary chromaffin granules. Studies in our laboratory demonstrated
      that catestatin acts at the nicotinic acetylcholine receptor to inhibit
      catecholamine secretion. However, the specificity of catestatin to exert
      nicotinic-cholinergic antagonism among its co-transmitters is not clearly known,
      nor is the potential effect of catestatin on multiple vesicle co-transmitters
      understood. AIM: Here we probed the specificity of catestatin's actions among its
      co-transmitters: catecholamines, ATP, and neuropeptide Y (NPY). METHODS: We
      studied the effects of each transmitter on exocytotic secretion of its co
      transmitters from PC12 chromaffin cells, stimulating secretion by triggering
      physiological pathways at multiple sites. RESULTS: We observed that, among
      chromaffin granule co-transmitters, only catestatin and NPY inhibited
      catecholamine release induced by nicotinic-cholinergic stimulation; catestatin
      was more than tenfold more potent than NPY in this setting. We also stimulated
      norepinephrine secretion by other chromaffin cell agonists: catestatin blocked
      norepinephrine release induced by nicotine, but not by other agents (such as
      membrane depolarization) acting at later stages in the secretory pathway, nor by
      agents acting on other receptor classes. By contrast, NPY acted less
      specifically, blocking norepinephrine release triggered by either nicotine or
      membrane depolarization. Catestatin inhibited nicotinic-cholinergic co-release of
      all classes of chromaffin granule co-transmitters: catecholamines, chromogranins,
      neuropeptides, and ATP. Naturally occurring variants of human catestatin
      (Gly364Ser and Pro370Leu) exhibited parallel changes in potency to inhibit
      secretion of catecholamines and ATP. CONCLUSION: We conclude that, among the
      chromaffin granule co-transmitters, catestatin acts as the most specific and
      potent inhibitor of physiological pathway (nicotinic-cholinergic) stimulated
      secretion. Furthermore, catestatin generally inhibits nicotinically triggered
      exocytotic release of multiple co-transmitters from chromaffin granules. The
      results have physiological and pharmacological implications for co-transmission
      in the sympathochromaffin system.

PMID- 16612253
TI  - Arterial plasma noradrenaline predicts left ventricular mass independently of
      blood pressure and body build in men who develop hypertension over 20 years.
AB  - BACKGROUND: Increased sympathetic activity may be an underlying mechanism in
      cardiovascular disease. It has been hypothesized that the degree of left
      ventricular (LV) hypertrophy is partly related to the blood pressure level, and
      partly to neurohormonal factors. The aim of this study was to investigate
      predictors of LV mass, including arterial plasma noradrenaline as an index of
      sympathetic activity, with particular emphasis on subjects who developed
      hypertension over a period of 20 years. METHODS: In a 20-year prospective study
      of middle-aged men, sustained hypertensives (n = 22), new hypertensives
      (crossovers) (n = 17) and sustained normotensives (controls) (n = 17) were
      examined both at baseline and after 20 years of follow-up (at ages 42.1 +/- 0.5
      and 62.3 +/- 0.6 years, respectively). Relationships between arterial plasma
      catecholamines, blood pressure and body mass index at baseline to left
      ventricular parameters by echocardiography at follow-up were investigated.
      RESULTS: Groups were homogeneous regarding age, gender, race and body build. The
      group of sustained hypertensives had significantly more LV hypertrophy (P =
      0.025) and diastolic dysfunction (P = 0.010). Among the crossovers, LV mass index
      was positively correlated to arterial plasma noradrenaline (r = 0.50, P = 0.043)
      and body mass index (BMI) (r = 0.51, P = 0.039) and showed a positive trend with
      systolic blood pressure (SBP) at baseline. Arterial plasma noradrenaline (beta =
      0.47) was found to predict LV mass index after 20 years independently of BMI
      (beta = 0.45) and SBP (beta = 0.22) at baseline (R adjusted = 0.345, P = 0.037).
      Such a relationship was not found in the controls or in the sustained
      hypertensives, of which 16 were treated with antihypertensive drugs. CONCLUSIONS:
      Arterial plasma noradrenaline at baseline, as an index of sympathetic activity,
      predicts LV mass at follow-up independently of systolic blood pressure and body
      build in middle-aged men who developed hypertension over a period of 20 years.

PMID- 16612254
TI  - Antihypertensive drugs clonidine, diazoxide, hydralazine and furosemide regulate
      the production of cytokines by placentas and peripheral blood mononuclear cells
      in normal pregnancy.
AB  - BACKGROUND: Antihypertensive drugs such as clonidine, diazoxide, hydralazine and
      furosemide are used in the hypertensive disorders of pregnancy to control blood
      pressure, but it is not clear if they modulate the production of placental or
      circulating cytokines. OBJECTIVE: To examine the effect of pharmaceutical doses
      of well known antihypertensive drugs used for blood pressure control on the
      production of the cytokines interleukin (IL)-6, IL-10 and tumour necrosis factor
      (TNF)-alpha in placental tissue and peripheral blood mononuclear cells (PBMCs) in
      normal pregnancy. DESIGN: Placental biopsies were taken from the decidual surface
      of placentas after delivery of normal pregnancies (n = 6) and PBMCs were
      separated from the whole blood of normal term pregnant women (n = 7). Both
      villous explants and PBMCs were cultured with increasing concentrations of
      antihypertensive drugs. The dose effect of drugs on the production of placental
      and circulating cytokines (IL-6, IL-10 and TNF-alpha) were examined by enzyme
      linked immunosorbent assay. RESULTS: Placental production of IL-10 was not
      affected by clonidine, but decreased significantly after incubation of the tissue
      with diazoxide, hydralazine or furosemide. Production of IL-10 by PBMCs increased
      significantly: by from 3.4 +/- 2.7% [16.3 pg/ml (range 6.1-21.5 pg/ml)] to 24.5
      +/- 3.3% [30.4 pg/ml (range 16.9-34.8 pg/ml)] with increasing concentrations of
      clonidine (0.08-1.3 microg/ml), and by 8.8 +/- 3.5% [4.1 pg/ml (range 3.0-17.8
      pg/ml)] and 17.2 +/- 1.9% [22.6 pg/ml (range 13.2-23.2 pg/ml)] with lower doses
      of hydralazine (6.3 and 12.5 microg/ml) (all P values < 0.05). There was a
      stepwise reduction in production of TNF-alpha and IL-6 with increasing doses of
      diazoxide, hydralazine and furosemide by placentas and PBMCs from these women
      with normal pregnancies. CONCLUSION: Our data suggest that the antihypertensive
      drugs clonidine and hydralazine can stimulate production of the circulating anti
      inflammatory cytokine IL-10, whereas furosemide and diazoxide inhibit the
      production of this cytokine and the proinflammatory cytokines TNF-alpha and IL-6
      by placentas and PBMCs.

PMID- 16612255
TI  - Association of CYP3A5 genotypes with blood pressure and renal function in African
      families.
AB  - OBJECTIVE: Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with
      blood pressure and salt sensitivity in humans. We determined whether CYP3A5
      polymorphisms are associated with ambulatory blood pressure (ABP) and with
      glomerular filtration rate (GFR) in African families. METHODS: Using a cross
      sectional design, 375 individuals from 72 families, each with at least two
      hypertensive siblings, were recruited through a hypertension register in the
      Seychelles (Indian Ocean). We analyzed the association between the CYP3A5 alleles
      (*1, *3, *6 and *7) and ABP, GFR and renal sodium handling (fractional excretion
      of lithium), from pedigree data, allowing for other covariates and familial
      correlations. RESULTS: CYP3A5*1 carriers increased their daytime systolic and
      diastolic ABP with age (0.55 and 0.23 mmHg/year) more than non-carriers (0.21 and
      0.04 mmHg/year). CYP3A5*1 had a significant main effect on daytime
      systolic/diastolic ABP [regression coefficient (SE): -29.6 (10.0)/-8.2 (4.1)
      mmHg, P = 0.003/0.045, respectively] and this effect was modified by age
      (CYP3A5*1 x age interactions, P = 0.017/0.018). For night-time ABP, the effect of
      CYP3A5*1 was modified by urinary sodium excretion, not by age. For renal
      function, CYP3A5*1 carriers had a 7.6(3.8) ml/min lower GFR (P = 0.045) than non
      carriers. Proximal sodium reabsorption decreased with age in non-carriers, but
      not in CYP3A5*1 carriers (P for interaction = 0.02). CONCLUSIONS: These data
      demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5*1
      carriers showing a higher age- and sodium- related increase in ABP than non
      carriers. The age effect may be due, in part, to the action of CYP3A5 on renal
      sodium handling.

PMID- 16612256
TI  - Alpha-adducin and angiotensin-converting enzyme polymorphisms in hypertension:
      evidence for a joint influence on albuminuria.
AB  - BACKGROUND: A single-nucleotide polymorphism (Gly460Trp) within the alpha-adducin
      gene (ADD1) may influence several renal phenotypes, including salt sensitivity,
      susceptibility to renal failure, the renal haemodynamics and confer a worse
      cardiovascular risks profile. However, its relationship with microalbuminuria, a
      marker of early renal and cardiovascular damage and an independent predictor of
      morbid events in hypertension, is unknown. For this reason, we related the ADD1
      genetic polymorphism to urine albumin levels and other clinical variables in
      essential hypertensive men. The angiotensin-converting enzyme (ACE)
      insertion/deletion (ID) polymorphism was also evaluated because of its
      interactive potential with the ADD1 genotype. METHODS: Albuminuria (three
      overnight collections), echocardiographic left ventricular mass index, blood
      pressure, body mass index, renal function, glucose and lipids were measured in
      238 genetically unrelated, never treated, uncomplicated Caucasian essential
      hypertensive men. Polymerase chain reaction or a 5' nuclease assay were used to
      characterize the ACE ID and ADD1 Gly460Trp variants, respectively. RESULTS:
      Microalbuminuria (albuminuria >or= 15 microg/min) was more frequent in patients
      with the ACE DD variant, but only in those with a ADD1 Gly460Gly background. In
      contrast, urine albumin did not differ by ACE ID genotype in the presence of
      mutated ADD1 Trp alleles. ADD1 polymorphisms per se were not associated with
      albuminuria. Cardiovascular, renal, metabolic parameters were homogeneously
      distributed among different genetic backgrounds. CONCLUSIONS: ACE DD and ADD1
      Gly460Gly polymorphisms may jointly influence albuminuria in hypertensive men,
      460Gly homozygosis facilitating or, possibly, the 460Trp allele mitigating the
      noxious renal impact of the ACE DD genotype. The data highlight further the
      complex pathophysiological implications of microalbuminuria in hypertension.

PMID- 16612257
TI  - The effect of sodium and angiotensin-converting enzyme inhibition on the classic
      circulating renin-angiotensin system in autosomal-dominant polycystic kidney
      disease patients.
AB  - BACKGROUND: It has been suggested that inappropriate stimulation of the renin
      angiotensin system (RAS) is responsible for the increase in blood pressure that
      occurs in autosomal-dominant polycystic kidney disease (ADPKD) before the
      development of renal failure. However, the interpretation of previous studies in
      ADPKD patients is confounded by inadequate matching with control populations for
      blood pressure and renal function, or failure to control the sodium intake of
      participants. METHODS: A double-blind, placebo-controlled study of two different
      sodium intakes (350 and 50 mmol/day for 5 days) in a group of 11 hypertensive
      ADPKD patients and eight matched control subjects with essential hypertension. In
      addition, blood pressure and hormonal responses were measured after the
      administration of the angiotensin-converting enzyme inhibitor enalapril for 3
      days. RESULTS: Blood pressure and hormonal responses of the RAS after a reduction
      in sodium intake and after the administration of enalapril were identical in
      ADPKD patients and controls. CONCLUSIONS: Activation of the classic circulating
      RAS is no greater in hypertensive ADPKD patients than in individuals with
      essential hypertension.

PMID- 16612258
TI  - Lipoic acid supplementation prevents cyclosporine-induced hypertension and
      nephrotoxicity in spontaneously hypertensive rats.
AB  - BACKGROUND: Cyclosporine (CsA) has significantly improved long-term survival
      after organ transplantations. Hypertension and nephrotoxicity are common side
      effects during CsA treatment and are aggravated by high salt intake. OBJECTIVE:
      To examine whether lipoic acid (LA), a natural antioxidant that scavenges
      reactive oxygen species and regenerates/recycles endogenous antioxidants, could
      prevent CsA-induced hypertension and nephrotoxicity. METHODS: Six-week-old
      spontaneously hypertensive rats (SHR) on a high-sodium diet (NaCl 6%) received
      CsA [5 mg/kg subcutaneously (s.c.)] alone or in combination with LA (0.5% w/w)
      for 6 weeks. Blood pressure, arterial functions, and tissue morphology were
      determined. Immunohistochemistry, quantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR) and high-pressure liquid chromatography were used for
      kidney and heart samples. RESULTS: CsA induced severe hypertension, cardiac
      hypertrophy, endothelial dysfunction, and pronounced albuminuria. Histologically,
      the kidneys showed severe thickening of the media of the afferent arteries with
      fibrinoid necrosis, perivascular monocyte/macrophage infiltration and
      nitrotyrosine overexpression. CsA induced the expression of fibrogenic connective
      tissue growth factor both in the heart and kidneys. The detrimental effects of
      CsA were associated with upregulation of myocardial atrial natriuretic peptide
      (ANP) mRNA expression, paradoxical activation of the renin-angiotensin system
      (RAS), induction of renal reduced nicotinamide-adenine dinucleotide phosphate
      (NADPH) oxidase, and overexpression of oxidative stress-induced transcription
      factor NRF2. LA lowered blood pressure, ameliorated cardiac hypertrophy and
      endothelial dysfunction, and totally normalized albuminuria. In LA-treated rats,
      renal and cardiac morphologies were indistinguishable from those of SHR controls.
      CsA-induced myocardial ANP and connective tissue growth factor (CTGF) mRNA
      overexpression, RAS activation, NADPH oxidase induction, and NRF2 overexpression
      were prevented by LA. LA induced the mRNA expression of gamma-glutamylcysteine
      ligase, the rate-limiting enzyme in glutathione synthesis, and markedly increased
      hepatic cysteine and glutathione concentrations. CONCLUSIONS: Our findings
      suggest a salutary role for lipoic acid supplementation in the prevention of CsA
      induced hypertension and nephrotoxicity, and underscore the importance of
      increased oxidative stress in the pathogenesis of CsA toxicity.

PMID- 16612259
TI  - Sympathetic nerve activity in renal transplant patients before and after
      withdrawal of cyclosporine.
AB  - BACKGROUND: It has been suggested that the increase in blood pressure observed in
      transplant patients treated with cyclosporine is mediated by cyclosporine-induced
      sympathoexcitation. However, the chronic effects of cyclosporine on sympathetic
      outflow in renal transplant patients have not been investigated. Therefore we
      studied sympathetic nerve activity and blood pressure before and 6 months after
      the withdrawal of cyclosporine in renal transplant patients. METHODS: Twenty-four
      renal transplant patients with histologically confirmed chronic allograft
      nephropathy (age 48 +/- 3 years, 60 +/- 10 months after transplantation) were
      included in the prospective study and randomly assigned to either withdrawal (n =
      12) or continuation (n = 12) of cyclosporine. Both groups received mycophenolate
      mofetil and prednisolone as additional immunosuppressants. At entry and 6 months
      later blood pressure, muscle sympathetic nerve activity (MSNA), and plasma
      norepinephrine were measured. To assess the potential influence of the diseased
      native kidneys, three renal transplant patients who had their native kidneys
      removed were studied before and after cyclosporine withdrawal. RESULTS: Mean
      arterial pressure decreased significantly in the cyclosporine-withdrawal group
      (95 +/- 4 versus 105 +/- 4 mmHg 6 versus 0 months, P < 0.05) but not in the
      cyclosporine-continuation group (103 +/- 3 versus 105 +/- 4 mmHg, NS). However,
      plasma norepinephrine and MSNA did not change significantly in either group (MSNA
      43 +/- 4 versus 44 +/- 3 and 38 +/- 5 versus 39 +/- 4 bursts/min in the
      cyclosporine-withdrawal and cyclosporine-continuation groups, NS). Graft function
      remained stable in both groups and in transplant patients who had their native
      kidneys removed MSNA did not decrease after cyclosporine withdrawal. CONCLUSION:
      The withdrawal of cyclosporine in renal transplant patients, receiving relatively
      low doses of cyclosporine, resulted in a substantial decrease in blood pressure.
      However, MSNA and norepinephrine did not change. This suggests that cyclosporine
      treatment does not cause chronic sympathetic activation that could explain the
      cyclosporine-induced blood pressure elevation in renal transplant patients.

PMID- 16612260
TI  - The interplay between haemodynamic load, brain natriuretic peptide and left
      atrial size in the early stages of essential hypertension.
AB  - OBJECTIVE: Left atrial (LA) enlargement is an index of adverse cardiovascular
      events. We sought to investigate any possible correlation between haemodynamic
      load, neurohumoral factors and LA size in the early stages of essential
      hypertension. METHODS: We studied 94 consecutive middle-aged subjects, with newly
      diagnosed stage I-II essential hypertension without left ventricular (LV)
      hypertrophy and 34 age and sex-matched normotensive individuals. Ambulatory blood
      pressure (BP) monitoring, plasma levels of brain natriuretic peptide (BNP),
      metabolic profile and left atrial volume index (LAVI), an echocardiographic
      measurement of LA volume indexed for the body surface area, constituted the work
      up of all subjects. RESULTS: Hypertensive compared with normotensive subjects had
      significantly increased office and ambulatory systolic and diastolic BP (P <
      0.0001 for all cases) as well as body mass index and waist-to-hip ratio (P < 0.05
      for both cases). BNP levels were greater in hypertensive compared with
      normotensive subjects but were not statistically significant (20.4 versus 17.1
      pg/ml, P = NS). Hypertensive compared with normotensive subjects also had
      significantly increased LV mass index (105 versus 84 g/m, P < 0.0001), LA
      diameter (39 versus 36 mm, P < 0.0001), and LAVI (22 versus 19 ml/m, P < 0.05).
      In the hypertensive population, LAVI exhibited significant positive relationships
      with office systolic BP, ambulatory pulse pressure, LV mass index and BNP. In
      multiple linear regression analysis only LV mass index and BNP were significantly
      associated with LAVI (beta = 0.298, P = 0.030 and beta = 0.322, P = 0.009,
      respectively). CONCLUSIONS: Increased LAVI, closely associated with LV mass index
      and BNP, was still found in the early stages of essential hypertension. However,
      the clinical significance of these findings remains to be elucidated in future
      studies.

PMID- 16612261
TI  - Blood pressure normalization is associated with normal left ventricular mass but
      not carotid geometry: the ICARe Dicomano Study.
AB  - OBJECTIVE: While many studies have examined the relation between antihypertensive
      treatment and ventricular hypertrophy, relatively few data are available
      regarding changes in arterial structure due to blood pressure reduction.
      Therefore, we compared normotensive to untreated hypertensive subjects to
      uncontrolled (treated with elevated blood pressure values) or controlled (treated
      with normal blood pressure values) hypertensive older subjects. PATIENTS:
      Community-dwellers (age >or= 65 years) of a small town in Italy (Dicomano)
      underwent extensive clinical examination, echocardiography, carotid
      ultrasonography, and applanation tonometry. Of the 614 participants, 173 subjects
      were normotensive; among the hypertensive subjects, 225 were untreated (51%), 177
      (40%) were uncontrolled, and only 39 (9%) were controlled. RESULTS: The majority
      of treated hypertensive subjects were on monotherapy (82%). Subjects with a
      history of coronary artery disease or stroke were more frequently treated.
      Controlled hypertensives had left ventricular mass index similar to normotensives
      but lower than uncontrolled and untreated hypertensives. There were no
      differences among the three hypertensive groups in carotid artery structure. Only
      the pressure-independent stiffness index was reduced in the treated hypertensive
      subjects compared to untreated hypertensives, with no difference between
      controlled and uncontrolled subjects. CONCLUSIONS: In our community-based, older
      population, antihypertensive treatment was associated with a normal left
      ventricular mass only when blood pressure was well controlled. In contrast,
      carotid artery remodeling and atherosclerosis were independent of
      antihypertensive treatment as well as of achievement of satisfactory blood
      pressure control. However, antihypertensive treatment was associated with
      significantly higher carotid compliance even in the absence of detectable changes
      in carotid structure.

PMID- 16612262
TI  - Estimation of attributable burden of disease: authors' reply.

PMID- 16612263
TI  - Copper and silver wiring in hypertensive retinopathy.

PMID- 16612264
TI  - Monoclonal and polyclonal antibody therapy for treating acute rejection in kidney
      transplant recipients: a systematic review of randomized trial data.
AB  - BACKGROUND: We performed a comprehensive systematic review to determine the
      relative benefits and harms of widely used interventions used to treat acute
      rejection in kidney transplant recipients: monoclonal or polyclonal antibodies
      (Ab). METHODS: Databases and conference proceedings were searched for eligible
      trials in all languages, and two reviewers, working independently, assessed
      trials for eligibility and quality, and extracted data. Results are expressed as
      relative risk (RR) with 95% confidence intervals (CI). RESULTS: Twenty-one trials
      (49 reports) were identified. Most trials were small, incompletely reported,
      especially for potential harms, and did not define outcome measures adequately.
      Fourteen trials (965 patients) compared therapies for first rejection episodes
      (eight Ab versus steroid, two Ab versus another Ab, and four other comparisons)
      In treating first rejection, Ab was better than steroid in reversing rejection
      (RR 0.57; CI 0.38-0.87) and preventing graft loss (death-censored RR 0.74; CI
      0.58-0.95) but there was no difference in preventing subsequent rejection (RR
      0.67; CI 0.43-1.04) or death (RR 1.16; CI 0.57-2.33) at 1 year. Seven trials (422
      patients) investigated Ab treatment of steroid-resistant rejection (four Ab vs.
      another Ab, one different doses Ab, one different formulation Ab, two other
      comparisons). There was no benefit of muromonab-CD3 over ATG or ALG in reversing
      rejection (RR 1.32; CI 0.33-5.28), preventing subsequent rejection (RR 0.99; CI
      0.61-1.59) or preventing graft loss (RR 1.80; CI 0.29-11.23) or death (RR 0.39;
      CI 0.09-1.65). CONCLUSIONS: Given the clinical problem caused by acute rejection,
      comparable data are sparse, and clinically important differences in outcomes
      between widely used interventions have not been excluded. Standardized
      reproducible outcome criteria are needed.

PMID- 16612265
TI  - Could more effective use of kidneys recovered from older deceased donors result
      in more kidney transplants for older patients?
AB  - In the face of a severe shortage of kidneys from deceased organ donors that
      limits access to transplantation for many patients, about one of every seven
      kidneys (more than 1,500 each year) recovered from deceased donors in the United
      States are not transplanted. Eurotransplant, which coordinates organ distribution
      for six countries and a population of about 118 million, discards only one of
      every 20 kidneys procured for transplantation. We compared kidney procurement,
      transplants, and discards between January 2000 and June 2003 in the United States
      and in the Eurotransplant region using the Organ Procurement and Transplantation
      Network/United Network for Organ Sharing and Eurotransplant databases to examine
      differences that might account for this wide disparity.

PMID- 16612266
TI  - Is age the only determinant?

PMID- 16612267
TI  - What can we learn from discarded deceased donor kidneys?

PMID- 16612268
TI  - Should retrieved kidneys ever be discarded?

PMID- 16612269
TI  - Not all donors are equal.

PMID- 16612270
TI  - The protective effect of the liver: does it apply to the bowel too?

PMID- 16612271
TI  - Clinical trials of immunosuppression in lung transplantation: a coming of age.

PMID- 16612272
TI  - Incidence of second primary cancer in transplanted patients.
AB  - BACKGROUND: Solid organ transplanted patients have a three- to fourfold higher
      lifetime risk of developing a cancer than the general population. However, the
      incidence of a second primary cancer in transplanted patients has never been
      studied, despite the fact that the presence of regular follow-ups and the
      increased survival of these patients make them a very attractive model. METHODS:
      We investigated the incidence of a second primary cancer (SPC) in 7,636 patients
      who underwent a kidney, liver, lung or heart transplant between 1970 and 2004,
      and were followed-up for 51,819 person-years. RESULTS: During the follow-up, 499
      subjects developed a first cancer (annual incidence: 98.6 x 10,000 PY), and 22 of
      them developed a SPC (annual incidence: 3.9 x 10,000 PY). The annual incidence of
      a SPC in the transplanted patients who developed a first cancer was 107.8 x
      10,000 PY, giving a standardized incidence ratio of 1.1 (95% CI: 0.83-1.41).
      CONCLUSIONS: This result shows that the incidence of the SPC was the same as the
      incidence of a first cancer. Our study does not indicate an increased risk of SPC
      in transplanted subjects who already suffered a first malignancy.

PMID- 16612273
TI  - Plasma cell-rich rejection processes in renal transplantation: morphology and
      prognostic relevance.
AB  - BACKGROUND: Renal transplantation is the most effective therapy in end-stage
      renal disease. The prognosis of transplant survival is still determined by
      rejection. Morphologically, this involves interstitial rejection with potential
      development of vascular rejection (VR) and/or glomerular rejection processes,
      designated as transplant glomerulopathy (TGP). The cellular infiltrates are
      usually dominated by lymphocytes and macrophages in differing quantity,
      characterizing the severity of the rejection processes. METHODS: In 14% of the
      renal transplant biopsies and explants in our investigation (n = 399) plasma
      cells (PR) predominate in the cellular infiltrate. To determine whether the
      enrichment of PR has an impact on graft function or could even constitute an
      independent parameter for transplant survival, we analyzed 109 cases of
      transplanted patients matched for AR and CR and divided them into those rich and
      those nonrich in PR. RESULTS: In the group rich in PR, PR comprised 30% of all
      infiltrates in comparison to 5% in the group non-rich in PR. VR and TGP appeared
      significantly more often in PR-rich rejections (P = 0.0044). The group rich in PR
      had a significantly more adverse prognosis (P = 0.0024), especially if PR
      enrichment was observed in the chronic rejection processes (P = 0.0148). In the
      Cox proportional hazard model the occurrence of VR was the only independent
      factor. CONCLUSION: In itself, plasma-cell enrichment is not a prognostic marker,
      but it is an indicator of a more adverse outcome because it is often accompanied
      by the appearance or subsequent development of VR +/- TGP. The detection of PR
      rich rejection processes should therefore encourage the clinician to intensify
      the immunosuppressive schedule.

PMID- 16612274
TI  - Study of the impact of liver transplantation on the outcome of intestinal grafts
      in children.
AB  - BACKGROUND: Successful small bowel transplantation remains a challenge due to the
      septic and immune content of the gut. The possible beneficial role of the liver
      was assessed in pediatric recipients of isolated intestinal and liver intestinal
      combined transplantation, receiving the same immunosuppressive therapy. METHODS:
      Fifteen children who underwent small bowel transplantation (seven SbTx) or
      combined liver-small bowel transplantation (eight LSbTx) at a single center
      between 1994 and 1998 were retrospectively reviewed and compared with fifteen
      controls (eight normal and seven appendicitis as inflammatory control).
      Transplant and patient survival, acute rejection episodes were analyzed and
      compared. Epithelial apoptotic body counts (ABC) and NF-kB (p65), Caspase-3 and
      Bax intestinal immunostaining from days 0 to 20 after transplantation were
      assessed. RESULTS: Graft and patient survivals at 5 years were respectively 75%
      and 75% in LSbTx; 43% and 57% in SbTx (NS). Histological analysis showed higher
      ABC in LSbTx intestinal mucosa (P = 0.05 on day 5, P < 0.01 thereafter).
      Immunostaining of biopsies on day 0 after reperfusion showed different expression
      of NF-kB, Caspase-3 and Bax on endothelial (P < 0.05 for NF-kB and Bax),
      mononuclear (P < 0.05 for Bax) and epithelial cells in LSbTx and SbTx.
      CONCLUSIONS: Our results suggest a protective role of the liver toward intestinal
      transplantation even in absence of significative difference, probably due to the
      small number of children. Early changes in NF-kB immunostaining in the biopsies
      sampled on day 0, pointed to a possible beneficial effect of the liver in the
      very early phase following transplantation, perhaps through the differential
      control of ischemia-reperfusion.

PMID- 16612276
TI  - Improved renal function after conversion from tacrolimus/sirolimus to
      tacrolimus/mycophenolate mofetil in kidney transplant recipients.
AB  - BACKGROUND: There is limited data on the potential nephrotoxicity of sirolimus
      (SRL) and tacrolimus (TAC) in combination. METHODS: We reviewed the course of 97
      kidney transplant patients treated with SRL and reduced-dose TAC. Conversion from
      SRL to mycophenolate mofetil (MMF) was prescribed in a minority (n = 19) for
      various nonrenal side effects. We compared outcomes of converted patients to
      those remaining on TAC/SRL (n = 78). RESULTS: TAC levels were increased in
      converters (P = 0.009). Rejection rates were similar between groups over 18
      months (21% vs. 16%, p = ns). Serum creatinine (Cr) and MDRD glomerular
      filtration rate (GFR) were similar between groups at nadir and six-months, but at
      18 months the percent change from six-month Cr was +17% in non-converters vs. 
      10% in converters (P = 0.004 for the difference). The difference in GFR between
      groups at 18 months was also significant (P = 0.01). By multivariate analysis,
      only conversion to MMF was associated with a greater percent change in Cr from 6
      to 18 months (P = 0.015). Conversion to MMF also correlated with higher GFR at 18
      months independent of rejection, delayed graft function, and ethnicity.
      CONCLUSIONS: Conversion from TAC/SRL to TAC/MMF led to improved renal function
      despite increased TAC exposure after conversion.

PMID- 16612275
TI  - Comparison of mycophenolate mofetil and azathioprine for prevention of
      bronchiolitis obliterans syndrome in de novo lung transplant recipients.
AB  - BACKGROUND: There are no data on the effects of mycophenolate mofetil (MMF) on
      the incidence of bronchiolitis obliterans syndrome (BOS) in lung-transplant
      patients. This study attempted to determine whether MMF reduces the incidence of
      BOS in de novo lung transplant recipients compared with azathioprine (AZA).
      METHODS: This prospective, randomized, open-label, multicenter study compared the
      effects of MMF with AZA in combination with induction therapy, cyclosporine
      (Neoral) and corticosteroids in patients receiving their first lung transplant.
      Primary endpoint was incidence of BOS at 3 years. Secondary endpoints were
      incidence of acute rejection, time to first rejection event, and survival.
      RESULTS: The incidence of acute rejection and the time to first rejection event
      at 1 and 3 years did not differ between groups (54.1% vs. 53.8% and 56.6% vs.
      60.3% for MMF and AZA respectively). Survival at 1 year tended to be better in
      patients receiving MMF (88 vs. 80%, P = 0.07). At year 3, there was no difference
      in survival or in the incidence, severity or time to acquisition of BOS between
      the two groups. Treatment was generally well tolerated, however more patients
      withdrew from AZA treatment than from MMF (59.6% vs. 46.5%, P = 0.02). As a
      result, there was an imbalance in the observation times of the two groups (876 +/
      395 vs. 947 +/- 326 days). CONCLUSIONS: No differences were seen in the
      incidence of acute rejection or BOS in lung transplant recipients treated with
      MMF or AZA. This null result may have been influenced by the shorter observation
      time for AZA patients.

PMID- 16612277
TI  - Early cyclosporine C0 and C2 monitoring in de novo kidney transplant patients: a
      prospective randomized single-center pilot study.
AB  - BACKGROUND: C2 monitoring of cyclosporine (CsA) has been promoted as improving
      the results of organ transplantation. No randomized, controlled studies in de
      novo kidney transplant recipients are available. METHODS: Between June 2003 and
      August 2004, 160 consecutive cadaveric kidney recipients allocated to CsA,
      mycophenolate and steroids were randomized to either C0 or C2 monitoring of CsA
      for the first 3 weeks posttransplant. Both levels were measured, keeping the
      other level blinded until 3 weeks. Altogether, 1451 double measurements were
      done. The target C0 was 200-300 microg/L and C2 1500-2000 microg/L. From the
      fourth week on, only C0 monitoring was used. Median follow up time was 505 days.
      RESULTS: The overall 3-month rejection rate was 7.5% in Group C0 vs. 10.8% in
      Group C2 and the one-year graft survival rates were 92.5% vs. 94.6% (NS). Rate of
      delayed graft function was similar in the groups. Plasma creatinine tended to be
      higher in group C2 at 3 weeks, but not thereafter. During the first three weeks
      posttransplant, the mean CsA dose was 57%, mean C2 levels were 55%, and mean C0
      levels were 98% higher in group C2 than in group C0 (P < 0.00001). CONCLUSION:
      This pilot study showed no advantages of C2 monitoring but led to significantly
      higher CsA doses and blood levels than C0 monitoring.

PMID- 16612278
TI  - Liver retransplantation: a model for determining long-term survival.
AB  - BACKGROUND: Because of the worse results from retransplantation in relation to
      the initial liver transplantation, there is a need to refine the indication for
      retransplantation, such that fair distribution of this benefit is obtained.
      METHODS: This was a study of 139 patients who underwent liver retransplantation.
      Thirty variables were studied: 18 relating to the recipient and 12 to the donor.
      All the independent variables were initially compared with the length of survival
      using univariate analyses. Variables presenting significance were compared with
      the dependent variable of length of survival, to determine which factors were
      related to longer survival among patients, when evaluated together. RESULTS: A
      multivariate model for determining long-term survival among patients with
      retransplants was built up using the following variables: recipient's age,
      creatinine, urgency of retransplantation and early failure of the first graft.
      Through this multivariate model it was possible to determine a score that was
      categorized according to tertile distributions (below the 33rd percentile, score
      <24; 33rd to 66th percentile, 24 < or = score < or = 32; above the 66th
      percentile, score > 32). One-year, 3-year, and 5-year patient survival rates
      following retransplantation were respectively 85%, 82%, and 77% for scores <24;
      69%, 66%, and 61% for scores between 24 and 32; and 21%, 19%, and 16% for scores
      >32 (P < 0.0001). CONCLUSION: The variables of recipient's age, creatinine,
      urgency of retransplantation, and early failure of the initial transplantation
      were factors that were independently related to the long-term survival of
      patients with liver retransplants.

PMID- 16612279
TI  - Transplanted neonatal cardiomyocytes as a potential biological pacemaker in pigs
      with complete atrioventricular block.
AB  - BACKGROUND: Sinus node dysfunction and severe heart block are major indications
      for electronic pacemaker implantation. The aim of the present study was to
      investigate the feasibility of an alternative approach by using spontaneously
      excitable cell grafts to serve as a biological pacemaker. METHODS: Enzymatically
      isolated neonatal atrial cardiomyocytes (including sinus nodal cells) were
      grafted into the free wall of the left ventricle of 5 male pigs. In the control
      group (n = 4), the medium was used for injecting. Three weeks after the
      transplantation the pigs underwent catheter ablation of the atrioventricular (AV)
      node. Microelectrode technique was used to record the transmembrane action
      potential of myocytes from cell- and medium-injected preparations.
      Immunohistochemistry was used to verify the grafted cells and the establishment
      of the gap junctions between donor and host cardiomyocytes. RESULTS: After the
      creation of complete AV-block, a higher average idioventricular rate was observed
      in cell-grafted pigs than that in control pigs (89 +/- 13 vs. 30 +/- 11 bpm, P <
      0.05). Administering isoprenaline caused a significant increase in the
      idioventricular rate from 89 +/- 13 to 120 +/- 18 bpm in the cell-grafted animals
      (P < 0.05). Microelectrode recordings showed that the spontaneously beating rate
      was significantly higher in the cell-implanted than that in the control
      preparations (82 +/- 17 vs. 33 +/- 13 bpm, P < 0.05). Furthermore, the
      immunofluorescence microscopy identified the DAPI-labeled donor cells, and the
      connexin-43 and N-cadherin positive junctions between them and host
      cardiomyocytes. CONCLUSION: Grafted neonatal atrial cardiomyocytes are able to
      survive and integrate into the host myocardium, and show a pacing function that
      can be modulated by autonomic agents.

PMID- 16612280
TI  - Thymocyte/splenocyte-derived CD4+CD25+Treg stimulated by anti-CD200R2 derived
      dendritic cells suppress mixed leukocyte cultures and skin graft rejection.
AB  - BACKGROUND: CD200 delivers immunoregulatory signals following engagement of its
      receptor, CD200R. A family of CD200Rs (CD200R1-4) has been described. Spleen
      expresses cell surface CD200R1, while bone marrow shows predominantly expression
      of cell surface CD200R2/R3. We showed that dendritic cell precursors (DCp)
      cultured with anti-CD200R2/3 develop the capacity to induce CD4(+)CD25(+)
      regulatory T cells (Treg) from peripheral lymphocytes. We now characterize DCs
      involved in induction of antigen-specific Treg from thymocytes or peripheral T
      cells, and the properties of Treg cells maintained in long-term culture. METHODS:
      Bone marrow DCp (C3H or BL/6 origin) were cultured for 8 days with GMCSF, IL-4
      and anti-CD200R2, or with CD200Fc and a previously described peptide inhibitor of
      CD200R1 to allow preferential engagement of non-CD200R1 receptors by CD200. Mixed
      leukocyte cultures (MLCs) were initiated with allogeneic responder
      lymphocytes/thymocytes (BL/6 or C3H) and mitomycin-c treated DCs to induce Treg.
      Treg cells were maintained by reculture with DCs derived in the same manner and
      IL-2, cloned at limiting dilution, and tested for their ability to suppress MLCs
      and skin graft rejection in vivo. RESULTS: Foxp3(+) CD4(+)CD25(+) Treg were
      derived from 60-hr thymocyte and splenocyte T cell cultures using both DC
      populations. Cloned C3H Treg (Foxp3(+)) suppressed both C3H anti-BL/6 reactivity
      in a fresh MLC and rejection of BL/6 skin allografts in C3H recipients; the
      converse was true for BL/6 Treg. CONCLUSIONS: We conclude that CD200 triggering
      of bone-marrow DCs in the absence of CD200R1 engagement induces CD4(+)CD25(+)
      Treg, and these cloned antigen-specific Treg may have clinical utility.

PMID- 16612281
TI  - Slowing the progression of chronic allograft nephropathy by conversion from
      cyclosporine to tacrolimus: a randomized controlled trial.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) is a multifactorial process with
      immunologic and nonimmunologic factors. Because tacrolimus (Tac) has been
      ascribed a beneficial effect on some of these factors when compared to
      cyclosporine A (CyA), a randomized controlled trial was conducted to investigate
      whether conversion from CyA to Tac can ameliorate the progression of renal
      dysfunction in kidney transplant recipients (KTR) with CAN. METHODS: Of the 46
      patients with biopsy-proven CAN enrolled, 24 were converted from CyA to Tac,
      whereas 22 patients were maintained on CyA. Serum creatinine (SCrea), lipid
      profiles and an antihypertensive score (AHS) were determined after 3, 6 and 12
      months. AHS is based on the total number and dosages of antihypertensive
      medications used. SCrea and AHS were additionally evaluated at 36 months.
      RESULTS: SCrea was decreased in the Tac group (Tac(baseline): 297 +/- 67
      micromol/L; Tac(6): 261+/- 70 micromol/L, P < 0.001; Tac(12): 254 +/- 55
      micromol/L, P < 0.001; Tac(36): 255 +/- 78 micromol/L, P = 0.235), whereas a
      significant increase of SCrea was detected in the CyA group (CyA(baseline): 279
      +/- 77 micromol/L, CyA(12): 333 +/- 98 micromol/L, P < 0.001; CyA(36): 317 +/- 89
      micromol/L, P < 0.001). Compared to CyA therapy, SCrea in the Tac group declined
      after 12 and 36 months (P = 0.011 and 0.048, respectively) as well as AHS
      (Tac(12): 59 +/- 13, CyA(12): 83 +/- 14, P < 0.001; Tac(36): 60 +/- 12, CyA(36):
      84 +/- 14, P < 0.001). LDL cholesterol was lower in the Tac group after 12 months
      (Tac(12): 2.5 +/- 0.5 mmol/L, CyA(12): 3.5 +/- 0.6 mmol/L, P < 0.001).
      CONCLUSION: Conversion from CyA to Tac in KTR with CAN improves allograft
      function, lowers blood pressure, and reduces LDL cholesterol. This superior
      profile may translate into improved long-term graft survival.

PMID- 16612282
TI  - Suppression of the cell-mediated immune response by a Fas-immunoglobulin fusion
      protein.
AB  - INTRODUCTION: Immunosuppressive agents must not only be effective in impairing
      the host's allo-immune response, but should also be selective in targeting only
      those elements of the immune system activated by the allograft. The fact that
      allo-activated T cells express surface protein molecules that are not typically
      present on resting T cells can be exploited to specifically target this
      population. Fas ligand is one such molecule whose cell surface expression on T
      cells is dramatically up-regulated upon activation. METHODS: We constructed a
      murine fusion protein by linking the extracellular domain of Fas to the Fc region
      of IgG2a. The rationale being to selectively target activated T cells via binding
      of its Fas moiety to cell surface Fas ligand, and then to allow the Fc moiety to
      invoke its usual effector mechanisms resulting in the destruction of the allo
      activated T cell. Here, we describe the design and expression of Fas-IgG2a and
      characterize several key in vitro and in vivo properties of this fusion protein
      including its ability to impact on both cell-mediated immune responses and
      cellular apoptotic activity using a murine model of delayed-type
      hypersensitivity. RESULTS: In vitro, our Fas-IgG2a construct bound activated T
      cells via FasL and invoked cytotoxicity. In vivo, it demonstrated a prolonged
      half-life characteristic of an immunoglobulin-like molecule. Most significantly,
      it suppressed the cell-mediated immune response and diminished cellular apoptotic
      activity in lymphoid tissue in our murine model. CONCLUSION: Fas-IgG2a is a novel
      agent for delivering target-specific immunosuppression with potential
      applicability in the transplant setting.

PMID- 16612283
TI  - Role of flow cytometry to define unacceptable HLA antigens in lung transplant
      recipients with HLA-specific antibodies.
AB  - BACKGROUND: Antidonor HLA-specific antibodies have been associated with
      hyperacute rejection and primary graft failure in lung transplant recipients.
      Thus, transplant candidates with HLA-specific antibodies generally undergo
      prospective crossmatching to exclude donors with unacceptable HLA antigens.
      However, the need to perform a prospective crossmatch limits the donor pool and
      is associated with increased waiting list times and mortality. A virtual
      crossmatch strategy using flow cytometry, which enables precise determination of
      HLA-specific antibody specificity, was compared to prospective crossmatching in
      sensitized lung transplant candidates. METHODS: In all, 341 lung transplant
      recipients were analyzed retrospectively (April 1992 to July 2003). Sixteen
      patients with HLA-specific antibodies underwent transplantation based on flow
      cytometric determination of antibody specificity and 10 underwent prospective
      crossmatching. RESULTS: Freedom from bronchiolitis obliterans syndrome (BOS) at
      three years was similar in those undergoing a virtual crossmatch, those
      undergoing prospective crossmatching, and those without HLA-specific antibodies
      (80.4% +/- 13.4, 85.7% +/- 13.2, and 73.8% +/- 2.8, respectively, P = 0.88).
      Three-year survival was also comparable (87.5% +/- 8.3, 70.0% +/- 14.5, and 78.5%
      +/- 2.4, respectively, P = 0.31). Elimination of prospective crossmatching for
      sensitized patients was associated with a significant decrease in time on the
      waiting list (P < 0.01) and in waiting list mortality (P < 0.05). All 16 patients
      undergoing a virtual crossmatch had negative retrospective crossmatches.
      CONCLUSIONS: By carefully determining the specificity of HLA-specific antibodies,
      flow cytometry methodologies enable the prediction of negative crossmatch results
      with up to 100% accuracy, enabling the determination of appropriateness of
      donors. Using this virtual crossmatch strategy, crossmatching can be safely
      omitted prior to lung transplantation, thereby decreasing waiting list time and
      mortality rates for candidates with HLA-specific antibodies.

PMID- 16612284
TI  - Elicited antibodies in baboons exposed to tissues from alpha1,3
      galactosyltransferase gene-knockout pigs.
AB  - BACKGROUND: This study investigates anti-nonGal antibodies (Abs) in baboons after
      alpha1,3-galactosyltransferase gene-knockout (GalT-KO) pig heart transplantation
      (Tx). METHODS: Four baboons underwent pig heart Tx under chronic
      immunosuppression, which was discontinued after graftectomy. During follow-up,
      one baboon also received a pig splenocyte infusion. Hearts and splenocytes were
      from GalT-KO pigs (n = 3) or pigs with low Gal expression (Gal-low, n = 2), all
      of swine leukocyte antigen (SLA) dd haplotype. Several weeks after graftectomy,
      sera were tested by flow cytometry and cytotoxicity assay on porcine peripheral
      blood mononuclear cells (PBMC) for elicited anti-nonGal Abs. Sera were adsorbed
      on a Gal immunoaffinity matrix, and tested for SLA haplotype specificity using
      PBMC from SLA aa, cc, and dd haplotypes. RESULTS: Before heart Tx, no baboon had
      anti-nonGal Abs demonstrable by binding or cytotoxicity to GalT-KO PBMC. All four
      baboons developed anti-nonGal Abs after Tx, demonstrable by flow cytometry, and
      three sera from baboons showed cytotoxicity to GalT-KO PBMC of SLA(dd) haplotype.
      After adsorption of anti-Gal Abs, the elicited anti-nonGal Abs showed similar
      binding to PBMCs from pigs of all three haplotypes (SLA(dd), SLA(aa), SLA(cc)).
      CONCLUSIONS: Anti-nonGal Abs developed after GalT-KO pig heart Tx into baboons.
      The most potent of these antibodies appeared to detect antigens shared by the
      three pig haplotypes tested. It remains unclear whether these antibodies are
      directed towards shared SLA determinants or other pig antigens, and whether
      antibodies with specificity for allelic SLA determinants are also present, but at
      lower titer.

PMID- 16612285
TI  - T-reg mediated suppression of the allograft response in the draining lymph node.
AB  - We previously demonstrated that T-regs inhibit proliferation of graft-reactive T
      cells in the draining lymph node (DLN), suggesting that this site may be
      important for regulation. TCR transgenic mice (TS1) specific for viral
      hemagglutinin (HA) provided antigen-specific T cells for adoptive transfer into
      syngeneic Balb/c hosts bearing HA+ skin grafts. T-regs were obtained from
      (TS1xHA28)F1 mice known to have an expanded population of HA-specific T-regs. To
      determine whether the lymph node is an independent site of suppression, we
      developed a model in which donor antigen that migrates from the allograft to the
      DLN drives T-cell activation after graft removal. T-regs that did not encounter
      the allograft itself remained able to inhibit graft antigen-specific T-cell
      proliferation in the DLN. Alloantigen-induced regulation can occur in the absence
      of the graft. This finding identifies the DLN as a potentially critical site of
      regulation in the early posttransplant period.

PMID- 16612286
TI  - Disappearance of nephrotic syndrome in type 1 diabetic patients following
      pancreas transplant alone.

PMID- 16612287
TI  - Crisis in America: organ donation.

PMID- 16612288
TI  - Regional differences in outcomes for hospitalized injured patients.
AB  - BACKGROUND: Our goal was to use a hospital population-based data set that was a
      sample of all injured patients admitted to a hospital in the United States to
      develop universal measures of outcome and processes of care. METHODS: Patients
      with a primary discharge diagnosis of injury (ICD-9 800 to 959) in the
      HCUP/Nationwide Inpatient Sample for the years 1995 to 2000 were used to estimate
      the annual number of hospitalized injured patients. Using census data, we
      calculated age- and sex- adjusted average annual incidence rates for four census
      regions in the United States: Northeast, Midwest, South and West. Outcomes
      measured were annual rates per million populations of hospitalization rate, death
      rate, and potentially ineffective care (PIC) rate defined as >28 days of
      hospitalization ending in death. Length of stay (LOS) was calculated as total
      number of days annually hospitalized for injury for census regions per million
      populations. RESULTS: Incidence rates per million populations and 95% confidence
      intervals for rate of hospitalizations for injury were: Northeast, 5596 (5338
      5853); Midwest, 5516 (5316-5716); South, 5639 (5410-5869); West, 5307 (5071
      5543). Incidence rates per million populations and 95% confidence intervals for
      rate of in-hospital deaths were: Northeast, 129 (119-139); Midwest, 131 (122
      139); South, 141 (129-152); West, 114 (106-123). Incidence rates per million
      populations and 95% confidence intervals for rate of PIC were: Northeast, 11 (10
      13); Midwest, 5 (4-5); South, 6 (5-7); West, 4 (3-4). Incidence rates per million
      populations and 95% confidence intervals for hospital days were: Northeast, 34
      (32-36); Midwest, 30 (28-31); South, 30 (29-32); West, 26 (24-27). CONCLUSION:
      Regional differences in outcomes and processes of care for hospitalized injured
      patients exist and may be influenced by hospital characteristics and region of
      the country. Research to identify the factors that cause these hospital and
      regional variations is needed. These observations suggest that to develop a
      uniform standard for quality of care, it will be essential to have valid and
      robust hospital population-based measures.

PMID- 16612289
TI  - Identification of expression patterns associated with hemorrhage and
      resuscitation: integrated approach to data analysis.
AB  - BACKGROUND: Although transcriptional profiling is a well-established technique,
      its application to systematic studying of various biological phenomena is still
      limited because of problems with high-volume data analysis and interpretation.
      This research project's objective was to create a comprehensive summary of
      changes in gene expression after hemorrhagic shock (HS), reliant and impartial of
      multiple variables, such as resuscitation treatments, organ analyzed, and time
      after impact. METHODS: Rat model of severe (40% total blood loss) HS was
      employed. Hemorrhagic shock was treated with 6 different resuscitation
      strategies: (1) racemic lactated Ringer's (DL-LR); (2) L-lactated Ringer's (L
      LR); (3) ketone Ringer's (KR); (4) pyruvate Ringer's (PR); (5) 6% hetastarch
      (Hex); (6) 7.5% hypertonic saline (HTS). Nonresuscitated and nonhemorrhaged rats
      served as controls. Ketone and pyruvate Ringer solutions were identical to the
      lactated Ringer's solution except for equimolar substitution of lactate with beta
      hydroxybutyrate and sodium pyruvate, respectively. Total RNA from liver, lung,
      and spleen was isolated immediately (0 hour) and 24 hour postresuscitation. Each
      organ, time point and treatment was profiled using individual cDNA array (1,200
      genes), to produce 183 separate data files. Methods of analysis included one-way
      and unbalanced factorial ANOVA, Sokal-Michener average linkage clustering and
      contextual mapping. RESULTS: : Unresuscitated HS produced the highest number (56)
      of upregulated expressions in spleen and lungs. HEX and HTS affected mostly
      pulmonary genes (22 and 9). Fourteen genes changed in response to combination of
      all three factors: treatment, organ, and time. Eighteen genes were identified as
      treatment-specific. Fifteen genes adjusted expression 24 hour post-treatment. The
      largest number of genes with altered expression (168) responded differently in
      all three organs. In this study 15 gene clusters were pinpointed. Contextual
      mapping identified novel and confirmed known pathways contributing to
      hemorrhage/resuscitation. CONCLUSIONS: We have reliably identified genes and
      pathways that are affected by HS and are responsive to resuscitation. Gene
      expression in various organs is affected differentially by HS, which can be
      further modulated by the choice of resuscitation strategy.

PMID- 16612290
TI  - A practical application of practice-based learning: development of an algorithm
      for empiric antibiotic coverage in ventilator-associated pneumonia.
AB  - BACKGROUND: Development of practice-based learning (PBL) is one of the core
      competencies required for resident education by the Accreditation Council for
      Graduate Medical Education, and specialty organizations including the American
      College of Surgeons have formed task forces to understand and disseminate
      information on this important concept. However, translating this concept into
      daily practice may be difficult. Our goal was to describe the successful
      application of PBL to patient care improvement with development of an algorithm
      for the empiric therapy of ventilator-associated pneumonia (VAP). METHODS: The
      algorithm development occurred in two phases. In phase 1, the microbiology and
      timing of VAP as diagnosed by bronchoalveolar lavage was reviewed over a 2-year
      period to allow for recognition of patterns of infection. In phase 2, based on
      these data, an algorithm for empiric antibiotic coverage that would ensure that
      the large majority of patients with VAP received adequate initial empiric therapy
      was developed and put into practice. The period of algorithm use was then
      examined to determine rate of adequate coverage and outcome. RESULTS: : In Phase
      1, from January 1, 2000 to December 31 2001, 110 patients were diagnosed with
      VAP. Analysis of microbiology revealed a sharp increase in the recovery of
      nosocomial pathogens on postinjury day 7 (19% < day 7 versus 47% > or = day 7, p
      = 0.003). Adequate initial antibiotic coverage was seen in 74%. In Phase 2, an
      algorithm employing ampicillin- sulbactam for coverage of community- acquired
      pathogens before day 7 and cefipime for nosocomial coverage > or =day 7 was then
      employed from January 1, 2002 to December 31, 2003. Evaluation of 186 VAP cases
      during this interval revealed a similar distribution of nosocomial cases (13% <
      day 7 versus 64% > or = day 7, p < 0.0001). Empiric antibiotic therapy was
      adequate in 82% of cases <day 7 and 85% of cases > or =day 7: overall accuracy
      improved to 83% (p = 0.05). Mortality from phase 1 to phase 2 trended toward a
      decrease (21% versus 13%, p = 0.1). CONCLUSIONS: Application of the concept of
      PBL allowed for identification of local patterns of infection and development of
      an institution specific treatment algorithm that resulted in >80% adequate
      initial empiric coverage for VAP with a trend toward decreased mortality. PBL
      allows for alteration in practice based on local patterns and outcomes and has
      the potential to improve patient care.

PMID- 16612291
TI  - Timing of pulmonary emboli after trauma: implications for retrievable vena cava
      filters.
AB  - BACKGROUND: Four recent reports of the retrieval of optional vena cava filters
      (VCF) in trauma patients had average implant durations of 10, 19, and 19 days
      (one not specified). Two patients in these studies had pulmonary emboli after VCF
      removal. No evidence-based guidelines exist on the appropriate time to remove
      optional VCF. The purpose of this study was to examine the timing of pulmonary
      emboli (PE) and determine the optimal time to remove optional VCFs. METHODS: A
      multicenter retrospective chart review of trauma patients who had a postinjury PE
      between January 2001 and December 2004 was performed. We examined the
      demographics, prophylaxis at the time of PE (pharmacologic [unfractionated or low
      molecular weight heparin] or sequential compression devices [SCD]), diagnostic
      test used, timing of PE from the date of injury, and survival outcome. RESULTS:
      In all, 146 patients were identified, mean age 45.1 (+/- 21.1 SD); Injury
      Severity Score 18.0 (+/- 12.1 SD). Diagnosis was obtained by spiral computed
      tomography (N = 93), pulmonary arteriogram (N = 18), V/Q (N = 26), autopsy (N =
      6), clinical (N = 6), and unknown (N = 3). Overall mortality was 17.8% (N = 26).
      Pulmonary embolism was felt to contribute to or was the cause of death in 85% (N
      = 22) of these patients. Two late PE deaths occurred (days 21 and 43). Sixty
      (37%) patients had pharmacologic prophylaxis at the time of PE and 83 (50.9%) had
      SCDs. Average time from injury to PE was 7.9 days (+/- 8.1 SD), the longest being
      43 days postinjury. Eleven percent of PE occurred after 21 days, including fatal
      PE. CONCLUSIONS: Clinical criteria defining the time to remove optional VCFs
      without exposing patients to the risk of PE by removing a filter too soon should
      be determined.

PMID- 16612292
TI  - Norepinephrine modulates the inflammatory and proliferative phases of wound
      healing.
AB  - BACKGROUND: Injury results in the massive release of norepinephrine (NE) into the
      peripheral circulation. Recent investigations have demonstrated functional
      adrenoreceptors on the cellular mediators of cutaneous wound healing and NE
      induced phenotypic alterations in immune cells have been demonstrated in vitro.
      Despite this, there is little description of how NE might alter the phases of
      wound healing in vivo. The purpose of this study was to compare cutaneous wound
      healing in norepinephrine-intact and norepinephrine-depleted mice. METHODS:
      Norepinephrine-depleted (NED) mice were generated by chemical axotomy with 6
      hydroxydopamine and compared with norepinephrine-intact (NEI) animals (n = 6-12
      per group, per time point). Using an excisional wound model, neutrophil
      recruitment was measured by myeloperoxidase assay. Macrophage recruitment and
      angiogenesis were measured by immunohistochemistry and re-epithelialization was
      determined histologically. The development of incisional wound disruption
      strength was determined over time. Finally, macrophage scavenger function was
      assessed by an in vitro latex bead phagocytosis assay. RESULTS: Wounds from NEI
      mice demonstrated greater neutrophil infiltration than NED wounds (24, 72 hours;
      p < 0.05). Wound macrophage recruitment was initially higher in NEI animals (24
      hours, p < 0.05), but was eventually surpassed by that of NED animals (120 hours,
      p < 0.05). Angiogenesis was decreased while re-epithelialization was accelerated
      in NEI animals (p < 0.05). Wound disruption strength and macrophage scavenger
      function were unaltered between NED and NEI mice. CONCLUSIONS: Norepinephrine
      modulates the inflammatory and proliferative phases of wound healing in a
      temporally defined, cell-specific manner. By increasing recruitment of innate
      immune cells and expediting wound closure, norepinephrine appears to play a
      protective role in defense against infection.

PMID- 16612293
TI  - Sixteen-slice computed tomographic angiography is a reliable noninvasive
      screening test for clinically significant blunt cerebrovascular injuries.
AB  - BACKGROUND: In light of their potential for devastating consequences, a
      liberalized screening approach for blunt cerebrovascular injuries (BCVI) is
      becoming increasingly accepted. The gold standard for diagnosis of BCVI is
      arteriography (ART), but noninvasive diagnostic alternatives offer clear
      advantages. Prospective comparative studies found that computed tomographic
      angiography (CTA) was unreliable in detecting BCVI. However, with advanced CTA
      technology, it has become more difficult to justify ART in asymptomatic patients.
      We implemented a liberal screening protocol for BCVI, employing 16-slice CTA. We
      hypothesized that CTA would detect all clinically significant BCVI. METHODS:
      Patients undergoing computed tomography scanning for cranial or cervical trauma,
      as well as those with high-risk injury mechanisms or patterns, had craniocervical
      CTA performed. Abnormal CTA studies were confirmed with ART. Patients were
      followed for signs or symptoms of ischemic neurologic events. RESULTS: Over an 11
      month period, 331 patients underwent CTA. Eighteen (5.4%) patients had a total of
      20 BCVI. There were 11 carotid and 9 vertebral artery injuries. Seven of nine
      (78%) vertebral injuries were associated with cervical spine fractures. Two
      patients who did not meet screening criteria had signs or symptoms of BCVI before
      CTA. No patient with normal CTA developed evidence of BCVI. CONCLUSIONS: CTA
      detected all clinically significant injuries during this study period. Liberal
      screening with 16-slice CTA is appropriate and is likely to miss very few
      significant injuries. A multicenter trial will help to clarify risk factors and
      the accuracy of noninvasive diagnostic modalities.

PMID- 16612294
TI  - Is the delay to surgery for isolated hip fracture predictive of outcome in
      efficient systems?
AB  - BACKGROUND: Adverse outcomes for patients with isolated hip fracture have been
      documented when preoperative delay is longer than 48 hours. An efficient system
      will have the capacity to repair all hip fractures within 48 hours. We
      hypothesized that in an efficient system, there would be a medical justification
      for a delay greater than 48 hours. The purpose of this study was to identify the
      causes and outcome of delay for hip surgery in an efficient system. METHODS: All
      patients with isolated hip fracture admitted to a regional trauma center from
      April 1993 to March 2003 were reviewed. Demographics, presence of comorbidity,
      preoperative delay, complications, and mortality were collected. Univariate and
      multivariate analysis were carried out. RESULTS: The cohort included 977
      patients. Overall mortality was 12.2%. Surgery was performed within 24 hours in
      53% of cases and within 48 hours in 87% of cases. The presence of comorbidity
      partly explained longer (>48 hours) surgical delays. Multivariate analysis
      revealed that age greater than 65, male sex, and the presence of pulmonary and
      cardiac comorbid conditions or an active cancer but not surgical delay were
      associated with mortality and complications. However, surgical delay was
      associated with longer postsurgical hospital stay, independently of the presence
      of comorbidity or increasing age. CONCLUSIONS: Preoperative delay does not entail
      adverse outcomes when the surgery is delayed to allow for treatment of comorbid
      medical conditions. Preoperative delay is associated with a longer hospital stay.
      The presence of comorbidity only partly explains preoperative delay and adverse
      outcomes. A prospective study coding for the severity of comorbid conditions and
      the justification of the preoperative delay will be required to fully elucidate
      the link between delay and outcome.

PMID- 16612295
TI  - Volume replacement with lactated Ringer's or 3% hypertonic saline solution during
      combined experimental hemorrhagic shock and traumatic brain injury.
AB  - BACKGROUND: The devastating effects of hypotension on head-trauma-related
      mortality are well known. This study evaluates the systemic and cerebral
      hemodynamic responses to volume replacement with 3% hypertonic saline (HSS) or
      lactated Ringer's solution (LR), during the acute phase of hemorrhagic shock (HS)
      associated with traumatic brain injury (TBI). METHODS: Fifteen dogs were assigned
      to one of three groups (n = 5, each) according to the volume replacement
      protocol, infused after TBI (brain fluid percussion, 4 atm) and epidural balloon
      to an intracranial pressure (ICP) higher than 20 mm Hg and HS, induced by blood
      removal to a mean arterial pressure (MAP) of 40 mm Hg in 5 minutes: Group
      HS+TBI+HSS (8 mL/kg of 3% HSS), HS+TBI+LR (16 mL/kg LR), and Group HS+TBI
      (controls, no fluids). We simulated treatment during prehospital and early
      hospital admission. Groups HS+ TBI and HS+TBI+LR received shed blood infusion to
      a target hematocrit of 30%. Measurements included shed blood volume, fluid volume
      infused to restore MAP, MAP, cardiac output, cerebral perfusion pressure,
      cerebral and systemic lactate, and oxygen extraction ratios. RESULTS: Fluid
      replacement with HSS 3% or LR promoted major hemodynamic benefits over control
      animals without luids. Cerebral perfusion pressure was higher than controls and
      similar between treated groups; however, HSS 3% infusion was associated with
      lower ICP during the "early hospital phase" and a higher serum sodium and
      osmolarity. CONCLUSION: In the event of severe head trauma and hemorrhagic shock,
      the use of HSS 3% and larger volumes of LR promote similar systemic and cerebral
      hemodynamic benefits. However, a lower ICP was observed after HSS 3% than after
      LR.

PMID- 16612296
TI  - Stent versus open surgery for acute and chronic traumatic injury of the thoracic
      aorta: a single-center experience.
AB  - BACKGROUND: Traumatic injuries of the thoracic aorta have a high morbidity and
      mortality. Treatment options include either open surgery or endovascular stent
      graft implantation. METHODS: We have reviewed retrospectively all our patients
      treated for acute and chronic traumatic injury of the thoracic aorta and compared
      the outcome of the endovascular versus open therapy. Age, gender, severity of
      injuries, interventional delay, perioperative morbidity, 30-day mortality, length
      of intensive care, and overall hospital stay were evaluated. RESULTS: In all, 46
      patients were treated over the past 14 years. Overall 30-day mortality was 16% in
      patients treated for acute or contained aortic ruptures (n = 31) and not
      significantly different after endovascular versus open repair (13.3% versus
      18.8%). There was no mortality in the patients receiving elective stent grafting
      or open surgery for chronic posttraumatic aortic aneurysms (n = 15). Conversion
      and/or operative revision following stent graft implantation occurred in three
      patients (12.5%). Neurologic complications were absent in the stent graft group
      (0 of 24), whereas paraplegia (n = 2) or minor neurologic (n = 3) deficits
      developed following open surgery (5 of 22; 22.7%; p = 0.013). Length of intensive
      care and overall hospital stay were significantly shorter for patients after
      elective stent graft treatment compared with open surgery (p = 0.045).
      CONCLUSIONS: According to our midterm results, minimally invasive endovascular
      repair for patients with acute traumatic ruptures and chronic posttraumatic
      aneurysms is an equally effective treatment option compared with open surgery,
      with advantages regarding perioperative neurologic complications and duration of
      hospital stay under elective circumstances.

PMID- 16612297
TI  - The delivery of critical care services in US trauma centers: is the standard
      being met?
AB  - BACKGROUND: Although there is substantial evidence supporting the benefits of an
      intensivist model of critical care delivery, the extent to which this model has
      been adopted by trauma centers across the United States is unknown. We set out to
      evaluate how critical care is delivered in Level I and II trauma centers and the
      extent to which these centers implement evidence-based patient care practices
      known to improve outcome. METHODS: All Level I and Level II trauma centers in the
      United States were surveyed using a previously validated questionnaire pertaining
      to the organizational characteristics of critical care units. Questions
      identifying the impediments to the implementation of an intensivist model of
      critical care delivery were added to the original survey. An intensivist model
      intensive care unit (ICU) was defined as one meeting all of the following
      criteria: a) the physician director was board certified in critical care; b) >50%
      of physicians responsible for care were board certified in critical care; c) an
      intensivist made daily rounds on the patients; and d) an intensive care team had
      the authority to write orders on the patients. The survey respondents were also
      queried regarding the extent to which they complied with evidence-based
      guidelines for care in the ICU. RESULTS: The overall response rate was 65% (295
      centers). Only 61% of Level I centers and 22% of Level II centers provided an
      intensivist model of critical care delivery. Sixty-nine percent of centers had a
      form of collaborative care with an intensivist, but few centers had dedicated
      intensivists without responsibilities outside the ICU. The most common reason
      cited for not involving an intensivist in the delivery of critical care services
      was a concern regarding a loss of continuity of care. There was limited
      implementation of evidence-based practices in the ICU; the model of critical care
      delivery had no effect on rates of implementation of these practices. CONCLUSION:
      The process of trauma center verification and designation should assure a high
      quality of trauma care. In keeping with these expectations of quality, the
      delivery of critical care services in trauma centers should evolve to a model
      that both includes the trauma surgeon in the care of the injured and allows for
      collaboration with a dedicated intensivist, who may or may not be a surgeon. The
      benefits of an intensivist model might be distinct from the utilization of
      evidence-based practices, suggesting that there might be incremental benefit in
      using these practices as markers of quality.

PMID- 16612298
TI  - Prospective study to evaluate the influence of FAST on trauma patient management.
AB  - BACKGROUND: Previous studies have concentrated on the accuracy of Focused
      Assessment with Sonography in Trauma (FAST), but evaluation of whether FAST
      changes subsequent management has not been fully assessed. METHODS: This
      prospective study compared 419 trauma admissions in two groups, FAST and no-FAST,
      for demographics, time of resuscitation, and action after resuscitation. The 194
      patients undergoing FAST had their management plan specified before, and
      confirmed after, FAST was performed to assess for change in management. To ensure
      scan consistency and to minimize bias, criteria were established to define an
      adequate FAST. RESULTS: FAST was performed in 194 patients (46%), assessing for
      free fluid. Management was changed in 59 cases (32.8%) after FAST. Laparotomy was
      prevented in 1 patient, computed tomography was prevented in 23 patients, and
      diagnostic peritoneal lavage was prevented in 15 patients. Computed tomography
      rates were reduced from 47% to 34% and diagnostic peritoneal lavage rates were
      reduced from 9% to 1%. CONCLUSIONS: FAST plays a key role in trauma, changing
      subsequent management in an appreciable number of patients.

PMID- 16612299
TI  - Predicting hospital mortality among injured children using a national trauma
      database.
AB  - PURPOSE: The purpose of this study was to develop a model that accurately
      predicts mortality among injured children based on components of the initial
      patient evaluation and that is generalizable to diverse acute care settings.
      Important predictive variables obtained in an emergency setting are frequently
      missing in even large national databases, limiting their effectiveness for
      developing predictions. In this study, a model predicting pediatric trauma
      mortality was developed using a national database and methods to handle missing
      data that may avoid biases that can occur restricting analyses to complete cases.
      METHODS: Records of pediatric patients included in the National Pediatric Trauma
      Registry (NPTR) between 1996 and 1999 were used as a training set in a logistic
      regression model to predict hospital mortality using vital signs, Glasgow Coma
      Scale (GCS) score, and intubation status. Multiple imputation was applied to
      handle missing data. The model was tested using independent data from the NPTR
      and National Trauma Data Bank (NTDB). RESULTS: Complete case analysis identified
      only GCS-eye and intubation status as predictors of mortality. A model based on
      complete case analysis had good discrimination (c-index = 0.784) and excellent
      calibration (Hosmer-Lemeshow c-statistic, 6.8) (p > 0.05). Using multiple
      imputation, three additional predictors of mortality (systolic blood pressure,
      pulse, and GCS-motor) were identified and improved model performance was
      observed. The model developed using multiple imputation had excellent
      discrimination (c-index, 0.947-0.973) in both test datasets. Calibration was
      better in the NPTR testing set than in the NTDB (Hosmer-Lemeshow c-statistic, 9.2
      for NPTR [p > 0.05] and 258.2 for NTDB [p < 0.05]). At a probability cutoff that
      minimized misclassification in the training set, the false-negative and false
      negative rates of the model were better than those obtained with either the
      Revised Trauma Score (RTS) or Pediatric Trauma Score using data from the NPTR
      testing set. Although the false-positive rates were lower with the RTS using data
      from the NTDB, the false-negative rates of the proposed model and the RTS were
      similar in this test dataset. CONCLUSIONS: Using multiple imputation to handle
      missing data, a model predicting pediatric trauma mortality was developed that
      compared favorably with existing trauma scores. Application of these methods may
      produce predictive trauma models that are more statistically reliable and
      applicable in clinical practice.

PMID- 16612300
TI  - Two worst injuries in different body regions are associated with higher mortality
      than two worst injuries in the same body region.
AB  - BACKGROUND: The Injury Severity Score (ISS) accounts for only one injury in each
      body region. The New Injury Severity Score (NISS) considers all injuries in a
      body region. Despite a big difference between the two scores in patients with
      multiple injuries, the NISS does not offer significant improvement in mortality
      prediction. This paper hypothesizes that two injuries in different body regions
      are associated with higher mortality than two injuries in the same body region,
      independently of injury severity. METHODS: The population consisted of 15,200
      patients with two or more injuries from the Quebec Trauma Registry, Canada,
      abstracted between 1998 and 2004. The two worst injuries were considered.
      Logistic regression analysis was used to assess the mortality odds ratio of
      having two worst injuries in different body regions (DR) compared with two worst
      injuries in the same body region (SR), while adjusting for the severity and the
      body region of the two worst injuries and age. RESULTS: A total of 5,869 patients
      (49%) had their worst injuries in DR. DR patients had 75% higher risk of
      mortality than SR patients (odds ratio = 1.75, 95% confidence interval = 1.42
      2.15). CONCLUSION: After accounting for differing injury severity, patients with
      their two worst injuries in different body regions have higher mortality than
      those with their two worst injuries in the same region. Results suggest that the
      observed effect is not due to a foible in the Abbreviated Injury Scale system but
      rather to physiologic, clinical, or organizational elements. The results of this
      study should be considered in the development of future injury severity
      instruments and may have implications for the care of patients with multiple
      injuries.

PMID- 16612301
TI  - Functional status and quality of life in survivors of injury treated at tertiary
      trauma centers: what are we neglecting?
AB  - BACKGROUND: The purpose of this study was to describe the functional status and
      quality of life (QOL) of patients at 12 months after injury. METHODS:
      Retrospective study consisting of patients treated at three tertiary trauma
      centers for injuries. Functional capacity (FC) was measured using the Sickness
      Impact Profile and QOL was measured using the Medical Outcomes Study Short Form
      (MOS SF-36) at approximately 12 months after the date of injury. RESULTS: There
      were 144 patients that fulfilled the study inclusion and exclusion criteria. The
      mean duration of follow-up was 1.3 years, with a range of 0.8 to 1.5 years. Age
      and gender were not associated with the FC or QOL. The mean(standard deviation)
      Injury Severity Score (ISS) was 18.9(9.4), whereas ISS category distribution was
      1 to 11 (22.9%), 12 to 24 (50.0%), and 25 to 49 (27.1%). Patients with an ISS of
      25 to 49 had significantly worse physical (p = 0.008) and total (p = 0.023)
      Sickness Impact Profile scores and had more physical functioning (p = 0.096),
      emotional role functioning (p = 0.080), and energy (p = 0.017) impairments when
      compared with those with an ISS less than 24. Patients injured in motor vehicle
      collisions had significantly impaired psychosocial function (p = 0.031), whereas
      those injured in falls had reduced quality of life scores for physical function
      (p = 0.089), physical role (p = 0.066), and mental health (p = 0.081).
      CONCLUSION: Patients who survive injuries experience residual impairments in FC
      and QOL for as long as 1 year after injury. Changes to the long-term management
      of these patients should be considered.

PMID- 16612302
TI  - The role of debridement and antibiotics in gunshot wounds to the spine.
AB  - BACKGROUND: The number of spinal cord injuries due to gunshot wounds continues to
      rise each year, and they currently rank third behind motor vehicle collisions and
      falls. Spine and wound infections pose difficult problems for
      transgastrointestinal gunshot wounds to the spine. METHODS: A retrospective
      review of 114 patients with low-velocity gunshot wounds to the spine was
      performed. Attention was paid to associated gastrointestinal (GI) tract injuries,
      antibiotic coverage, surgical intervention, and the development of spine and
      wound infections. RESULTS: Of 114 patients with gunshot wounds to the spine, 27
      (23.7%) sustained a concomitant GI tract injury and 87 (76.3%) did not. Four
      spine infections (4/114, 3.5%) and 23 wound infections (23/114, 20.2%) developed
      in our patient population. Spine infection (chi = 13.36, p < 0.001) and wound
      infection (chi = 12.94, p < 0.001) rates were significantly higher in
      transgastrointestinal gunshot wounds to the spine. Surgical treatment of the
      spine in patients with transgastrointestinal gunshot wounds showed a
      significantly higher rate of spinal infection than did nonsurgical treatment of
      the spine (p = 0.013, Cramer's V = 0.61). No significant difference in spine
      infection rate was seen with adequate versus inadequate antibiotic coverage in
      the trans- gastrointestinal subset (p = 1.00), or in the development of wound
      infections with spine surgery (p = 0.628) or varying antibiotic coverage (p =
      1.00). CONCLUSIONS: There is a significantly higher rate of spine and wound
      infections with trans-gastrointestinal gunshot wounds to the spine. These
      injuries, particularly those that involve the colon, put patients at risk for the
      development of spine infections after spinal surgery. Randomized controlled
      trials are necessary for the development of a specific protocol for intravenous
      antibiotic therapy in the setting of transgastrointestinal gunshot wounds to the
      spine.

PMID- 16612303
TI  - Cultured skin substitutes reduce requirements for harvesting of skin autograft
      for closure of excised, full-thickness burns.
AB  - BACKGROUND: Rapid and effective closure of full-thickness burn wounds remains a
      limiting factor in burns of greater than 50% of the total body surface area
      (TBSA). Hypothetically, cultured skin substitutes (CSS) consisting of autologous
      cultured keratinocytes and fibroblasts attached to collagen-based sponges may
      reduce requirements for donor skin, and morbidity from autograft harvesting and
      widely-meshed skin grafts. METHODS: To test this hypothesis, CSS were prepared
      from split-thickness skin biopsies collected after enrollment of 40 burn patients
      by informed consent into a study protocol approved by the local Institutional
      Review Boards of three participating hospitals. CSS and split-thickness skin
      autograft (AG) were applied in a matched-pair design to patients with full
      thickness burns involving a mean value of 73.4% of the TBSA. Data collection
      consisted of photographs, area measurements of donor skin and healed wounds after
      grafting, qualitative outcome by the Vancouver Scale for burn scar, and biopsies
      of healed skin. RESULTS: Engraftment at postoperative day (POD) 14 was 81.5 +/-
      2.1% for CSS and 94.7 +/- 2.0 for AG. Percentage TBSA closed at POD 28 was 20.5
      +/- 2.5% for CSS, and 52.1 +/- 2.0 for AG. The ratio of closed to donor areas at
      POD 28 was 66.2 +/- 8.4 for CSS, and 4.0 +/- 0.0 for each harvest of AG. Each of
      these values was significantly different between the graft types. Correlation of
      percent TBSA closed with CSS at POD 28 with percent TBSA full-thickness burn
      generated an r value of 0.37 (p < 0.0001). Vancouver Scale scores at 1 year after
      were not different for erythema, pliability, or scar height, but pigmentation
      remained deficient in CSS. CONCLUSIONS: These results demonstrate that CSS reduce
      requirements for donor skin harvesting for grafting of excised, full-thickness
      burns of greater than 50% TBSA with qualitative outcome that is comparable to
      meshed AG. Availability of CSS for treatment of extensive, deep burns may reduce
      time to wound closure, morbidity, and mortality in this patient population.

PMID- 16612304
TI  - Fixation of diaphyseal fractures with a segmental defect: a biomechanical
      comparison of locked and conventional plating techniques.
AB  - BACKGROUND: Locking plates are an alternative to conventional compression plate
      fixation for diaphyseal fractures. The objective of this study was to compare the
      stability of various plating with locked screw constructs to conventional
      nonlocked screws for fixation of a comminuted diaphyseal fracture model using a
      uniform, synthetic ulna. Locked screw construct variables were the use of
      unicortical or bicortical screws, and increasing bone to plate distance. METHODS:
      This biomechanical study compared various construct groups after cyclic axial
      loading and three-point bending. Results were analyzed via one-way analysis of
      variance. Displacements after cyclical axial loading and number of cycles to
      failure in cyclic bending were used to assess construct stability. RESULTS: The
      constructs fixed by plates with bicortical locked screws withstood significantly
      more cycles to failure than the other constructs (p < 0.001). Significantly less
      displacement occurred after axial loading with bicortical locked screws than with
      bicortical nonlocked screws. Increased distance of the plate from the bone
      surface, and use of unicortical locked screws led to early failure with cyclic
      loading for constructs with locked screws. CONCLUSIONS: These results support the
      use of plating with bicortical locked screws as an alternative to conventional
      plating for comminuted diaphyseal fractures in osteoporotic bone. Bicortical
      locked screws with minimal displacement from the bone surface provide the most
      stable construct in the tested synthetic comminuted diaphyseal fracture model.
      The results of this study suggest use of plates with unicortical screws for the
      described fracture is not recommended.

PMID- 16612305
TI  - Biomechanical evaluation of the less invasive stabilization system and the 95
      degree angled blade plate for the internal fixation of distal femur Fractures in
      human cadaveric bones with high bone mineral density.
AB  - BACKGROUND: The less invasive stabilization system (LISS) is an internal fixator
      that utilizes unicortical locked screws for fixation of distal femur fractures. A
      question is whether locked unicortical screw fixation is sufficient, when
      compared with a standard implant such as a blade plate. METHODS: Eight matched
      pairs of fresh-frozen cadaveric femora were instrumented with either the LISS or
      a 95-degree blade plate. A 4-cm supracondylar gap fracture model was created and
      all bone-implant constructs were tested to failure in axial loading. RESULTS: All
      constructs failed by plastic deformation of the implant. There was no significant
      difference between the LISS and the blade plate constructs with respect to load
      to failure. CONCLUSIONS: Despite unicortical fixation axial loading to failure of
      the LISS did not result in implant/screw pull-out neither proximally nor
      distally. However, there does not appear to be a biomechanical advantage of using
      the LISS as opposed to a blade plate in bones with high bone mineral density.

PMID- 16612306
TI  - Complications after plate fixation of phalangeal fractures.
AB  - PURPOSE: To assess the complications after plate fixation of phalangeal
      fractures, their correlation with the type of injury, and the outcome. METHODS:
      We retrospectively reviewed the clinical records and the x-rays of 54 consecutive
      patients with 64 phalangeal fractures treated by open reduction and plate
      fixation with regard to fracture healing, plate loosening or failure, infection,
      complex regional pain syndrome, pain, return to work, and range of motion.
      RESULTS: In 31 out of 54 patients (57%) and 33 out of 64 fractures (52%), one or
      more major complications occurred. Stiffness (definition is composite range of
      motion of metaphalangeal, proximal interphalangeal, and distal interphalangeal
      joints added together equaling <180 degrees) contributed the highest number (22
      patients, 24 fractures). The complication rates were not different whether the
      fracture was open or closed, if it was located in the proximal or middle phalanx,
      the presence or absence of an associated soft tissue lesion, and the patient's
      occupation. CONCLUSIONS: In spite of early mobilization, stiffness is the most
      frequent complication after open reduction and plate fixation of phalangeal
      fractures. The undue amount of scarring and adhesion may arise from the implant
      itself or the difficulty in finding the perfect mixture between the minimal
      surgical invasiveness and a sufficient restoration of skeletal stability.
      Otherwise, plate fixation of unstable and complex phalangeal fractures proved
      efficient and reliable, although not free of potential problems.

PMID- 16612307
TI  - Alteration of polymorphonuclear neutrophil surface receptor expression and
      migratory activity after isolation: comparison of whole blood and isolated PMN
      preparations from normal and postfracture trauma patients.
AB  - BACKGROUND: Post-traumatic MOF results from local tissue injury because of
      migration and activation of dysfunctional polymorphonuclear leukocytes (PMN).
      Although fracture surgery exacerbates the postinjury inflammatory response, it is
      usually beneficial. This study compared changes in PMN receptor expression and
      migratory activity, in whole blood and following PMN isolation. METHODS: IL-8
      mediated PMN migration and expression of CXCR-1, CD11b, and CD18 was studied in
      isolated and whole blood PMN in normal controls. Migration was studied at
      admission and day 5 after surgery in trauma patients undergoing fracture surgery.
      RESULTS: PMN isolation results in increased expression of surface receptors and
      enhanced migration in normal controls. In trauma patient samples, isolated PMN
      migration is enhanced after injury, but suppressed when migration from whole
      blood is studied, both after injury and fracture surgery. CONCLUSION: PMN
      isolation results in priming for migration, which has a relatively greater impact
      upon PMN in trauma patients. The observation that PMN activity may decline but
      priming potential remains enhanced is novel. Further refinements of whole blood
      and isolated PMN techniques are clearly warranted. This may help to resolve the
      mismatch in clinical and scientific experience in those patients with major
      fractures requiring surgical stabilization.

PMID- 16612308
TI  - Pulmonary endothelial permeability is increased by fluid from packed red blood
      cell units but not by fluid from clinically-available washed units.
AB  - BACKGROUND: Massive transfusions are a risk factor for acute respiratory distress
      syndrome (ARDS) in severely injured patients. Neutrophil priming has been
      proposed to be an integral part of the early inflammatory response to trauma. To
      complement that work, we studied another major cell type involved in
      inflammation: the endothelial cell. Our hypothesis was that soluble factors from
      units of leukoreduced packed red blood cells (PRBC) directly increase pulmonary
      endothelial permeability. We also determined whether fluid from clinically
      available washed PRBC units affects endothelial permeability. METHODS: As a
      measure of permeability, transendothelial electrical resistance (TER) was
      determined across monolayers of a human pulmonary microvascular endothelial cell
      line after addition of full-strength, diluted, and washed PRBC fluid. Monolayers
      were stained with phalloidin to assess intercellular space. Storage solution
      Adsol-1 was tested alone to determine additive component effects on TER. RESULTS:
      PRBC fluid decreased TER and increased intercellular space, both of which
      indicate an increase in endothelial monolayer permeability. PRBC fluid diluted to
      2% and washed PRBC fluid did not decrease TER and thereby did not change
      endothelial permeability. Likewise, Adsol-1 did not duplicate the dramatic
      decrease in TER seen with the PRBC fluid. CONCLUSIONS: Fluid from stored PRBC
      units contains a soluble, transferable factor that directly increases endothelial
      permeability. Fluid from washed PRBC units, currently available for patients with
      immunoglobulin A allergies, does not. This study complements previous work of
      others that demonstrated that neutrophil priming by PRBC fluid is abrogated by
      washing. Now that two cell types have been shown to respond more favorably to
      washed PRBC in vitro, clinical studies should be initiated to investigate whether
      use of washed PRBC reduces ARDS following transfusions in trauma patients.

PMID- 16612309
TI  - Nafamostat attenuated the impairment of fibrinolysis in animal sepsis model by
      suppressing the increase of plasminogen activator inhibitor type 1.
AB  - BACKGROUND: In endotoxemia, plasminogen activator inhibitor-1 (PAI-1) increases
      and develops clinical symptoms by suppressing fibrinolysis. We analyzed
      therapeutic advantage of nafamostat, a broad-range protease inhibitor, on
      fibrinolysis in an animal sepsis model. METHODS: Male Wister rats infused with
      lipopolysaccharide (LPS) (50 mg/kg) alone or together with nafamostat (0.1
      mg/kg/hr) for 4 hours were analyzed. RESULTS: Plasma PAI-1 (4.2: 4.0-5.0 ng/mL,
      median and interquartile range) increased after LPS infusion (3700: 3400-4000),
      which was attenuated by nafamostat (2300: 2100-2600, p < 0.05). Fibrin(ogen)
      degradation products after LPS injection (173: 152-182 microg/mL) were further
      elevated by nafamostat (205: 205-228, p < 0.05), Nafamostat attenuated
      polymorphonuclear neutrophils infiltration in the liver, and tended to suppress
      plasma tumor necrosis factor-alpha levels. Nafamostat did not affect thrombin
      generation, platelet count, markers of liver and kidney function, and overall
      mortality. CONCLUSIONS: Nafamostat appeared to improve impaired fibrinolysis by
      suppressing the increase of PAI-1 in plasma, though it did not largely improve
      clinical parameters.

PMID- 16612310
TI  - Effects of hyperglycemia and insulin therapy on outcome in a hyperglycemic septic
      model of critical illness.
AB  - BACKGROUND: The effects of hyperglycemia and insulin therapy on septic outcome
      have not been well studied. METHODS: Septic hyperglycemia was induced by infusion
      of TPN (254 kcal/kg x d) immediately following cecal ligation and puncture (CLP)
      surgery in rats. Animals (N = 109) were monitored for blood glucose and followed
      for survival for 4 days. Separate cohorts (N = 36) were sacrificed at 22 hours
      post-CLP and analyzed for cytokines/chemokines, hormones, and organ damage
      markers. The effects of insulin treatment on 4 day survival were also examined (N
      = 60). RESULTS: Hyperglycemic septic animals had significantly higher blood
      glucose (p < 0.0001), plasma proinflammatory cytokine levels, serum organ damage
      markers (p < 0.05) and reduced mean survival time (p < 0.001). Insulin treatment
      (2 IU/kg/hr) resulted in significantly lower blood glucose (p < 0.01) and
      improved 4 day survival (p < 0.03). CONCLUSIONS: Hyperglycemia is associated with
      greater morbidity and mortality in sepsis. Insulin therapy significantly improved
      survival suggesting that management of hyperglycemia with insulin may improve
      outcome in septic patients.

PMID- 16612311
TI  - Hyperglycemia has a stronger relation with outcome in trauma patients than in
      other critically ill patients.
AB  - BACKGROUND: Acute hyperglycemia is associated with adverse outcome in critically
      ill patients. Glucose control with insulin improves outcome in surgical intensive
      care unit (SICU) patients, but the effect in trauma patients is unknown. We
      investigated hyperglycemia and outcome in SICU patients with and without trauma.
      METHODS: A 12-year retrospective study was performed at a 12-bed SICU. We
      collected the reason for admission, Injury Severity Scores (ISS), and 30-day
      mortality rates. Glucose measurements were used to calculate the hyperglycemic
      index (HGI), a measure indicative of overall hyperglycemia during the entire SICU
      stay. RESULTS: In all, 5234 nontrauma and 865 trauma patients were studied.
      Trauma patients were younger, more frequently male, and had both lower median
      admission glucose (123 versus 133 mg/dL) and HGI levels (8.9 vs. 18.4 mg/dL) than
      nontrauma patients (p < 0.001). Mortality was 12% in both groups. Area under the
      receiver-operator characteristic for HGI and mortality was 0.76 for trauma
      patients and 0.58 for nontrauma patients (p < 0.001). In multivariate analysis,
      HGI correlated better with mortality in trauma patients than in nontrauma
      patients (p < 0.001). Head-injury and nonhead-injury trauma patients showed
      similar glucose levels and relation between glucose and mortality. CONCLUSIONS:
      The relation of hyperglycemia and mortality is more pronounced in trauma patients
      than in SICU patients admitted for other reasons. The different behavior of
      hyperglycemia in these patients underscores the need for evaluation of intensive
      insulin therapy in these patients.

PMID- 16612312
TI  - Kidney injury: an experimental investigation of blunt renal trauma.
AB  - BACKGROUND: The abdomen ranks third with regard to injured body regions, and
      urogenital trauma accounts for up to 10% of all abdominal injuries. Predictive
      numerical models are evolving as important tools for the development of
      preventative measures and preliminary clinical diagnostics. Such models require
      accurate biomechanical input data that at present is not sufficiently available.
      METHOD: The purpose of the present study was to determine the biomechanical
      response of whole, perfused porcine kidneys to blunt impact. Specifically of
      interest were the force-displacement characteristics of the organs, as well as
      the injury thresholds. Thirty nine young, adult pig kidneys (kidney mass 0.17 +/-
      0.02 kg) were infused with physiologic saline solution, and impacted on their
      dorsal surface by a freely swinging right cylindrical pendulum. Two impact masses
      (2.1 and 4.7 kg) were used at varying impact velocities and corresponding impact
      energies. Resulting injuries were graded according to the AAST injury scale, and
      injury was related to impact mass, impact velocity, and impact energy. RESULTS
      AND CONCLUSIONS: It was determined that injury was best predicted by impact
      energy, and that for a given impact energy the resulting injury severity was
      relatively independent of either impact mass or impact velocity. For a moderate
      to severe injury, an impact energy threshold of 4 J, or a corresponding strain
      energy density of 25 kJ/m, was established. This information is essential to the
      development and implementation of accurate, predictive computational trauma
      models.

PMID- 16612313
TI  - Comparing the biomechanical response of human and porcine kidneys to blunt
      trauma.

PMID- 16612314
TI  - Severe traumatic brain injury complicated by status asthmaticus: favorable
      neurological outcome despite excessive hypercapnia.

PMID- 16612315
TI  - Intracranial penetration of a glass piece through the temporal region in civilian
      head injury.

PMID- 16612316
TI  - Immediate diagnosis and nonoperative treatment of a pulmonary artery
      pseudoaneurysm after blunt traumatic injury.

PMID- 16612317
TI  - Delayed pancreaticoduodenal arterial pseudoaneurysmal formation after abdominal
      penetrating injury.

PMID- 16612318
TI  - Accessory spleen rupture in a patient with previous traumatic splenectomy.

PMID- 16612319
TI  - Closed traumatic avulsion of both flexor tendons in the ring finger.
AB  - Traumatic rupture of the deep flexor tendon is a well-recognized entity known as
      "jersey finger". However, simultaneous traumatic rupture or avulsion of both
      flexor tendons in a finger without pre-existing disease is extremely rare. Such
      an injury is presented and discussed here, with regards to the mechanism,
      location, and treatment in comparison with similar reports in the literature.

PMID- 16612320
TI  - Historical vignette: the introduction of arterial repair into the US Marine
      Corps, US Naval Hospital, in July-August 1952.

PMID- 16612321
TI  - An improvised wound closure system.
AB  - BACKGROUND: Skin stretching harnesses the same viscoelastic properties of the
      skin as expansion, with the difference that the forces are applied externally and
      not internally. An improvised system for wound closure is presented. METHOD: The
      system is assembled using silicone vascular loops used as sutures and the flow
      controllers of intravenous sets as locking devices. The wounds are gradually
      closed by increasing the tension applied by the devices. RESULTS: The system has
      been applied to nine traumatic wounds in six patients. The average size of the
      wounds was 70 cm; the average number of devices used was 4.3 (range, 1-9; median,
      3); the average time to achieve closure was 1.55 days (range, 0-2 days; median, 2
      days). CONCLUSION: This system permits the closure of wounds not suitable for
      closure by primary intention and avoids the use of skin grafts or flaps.

PMID- 16612322
TI  - Visceral torso computed tomography for clearance of the thoracolumbar spine in
      trauma: a review of the literature.
AB  - BACKGROUND: Accurate screening of the thoracolumbar spine (TLS) remains
      problematic in the care of trauma patients. The current standard of care for TLS
      screening is not clearly defined. In trauma patients undergoing computed
      tomography (CT) of the chest and or abdomen, compelling supportive evidence for
      reformatting and reusing this CT data to clear the thoracolumbar spine has
      accumulated over the last 3 years. The objective of this review was to identify
      and review all published studies comparing reformatted CT to traditional plain
      radiography for TLS clearance. METHODS: A Medline search for all English language
      articles published on this subject since 1980 identified seven studies. Each was
      classified according to the levels of evidence classification of the Agency for
      Health Care Policy and Research. The methodology of each study was reviewed for
      the CT protocol, utilization of radiologist blinding and whether historical
      dictated reports or de novo image readings were used for comparison. The
      sensitivity and specificity of each study and the gold standard utilized in its
      calculation was noted. Where available, detailed information regarding the missed
      injuries and their clinical relevance was abstracted for each study. RESULTS: All
      evaluated studies demonstrated superior sensitivity and interobserver variability
      for reformatted CT compared with plain radiographic screening. CT was also more
      accurate in localizing, classifying, and delineating the age, bony intrusion, and
      soft-tissue damage associated with the fracture. For studies with time-motion
      components, a protocol utilizing CT clearance was not only more accurate but
      faster and more economical. Screening with reformatted visceral CT data required
      no additional scan time or radiation exposure. CONCLUSION: The evidence to date
      demonstrates the superior sensitivity of reformatted visceral CT for detecting
      thoracolumbar spine injury. With no further patient movement, radiation exposure,
      cost, or time, trauma patients undergoing visceral CT can have their
      thoracolumbar spine promptly evaluated. Further prospective evaluation of the CT
      protocols to optimize visualization of both the viscera and the bone is
      warranted.

PMID- 16612323
TI  - Chance fracture of the second thoracic vertebra: case illustration.

PMID- 16612324
TI  - Surgical Critical Care (SCC).

PMID- 16612326
TI  - The multifaceted mismatch-repair system.
AB  - By removing biosynthetic errors from newly synthesized DNA, mismatch repair (MMR)
      improves the fidelity of DNA replication by several orders of magnitude. Loss of
      MMR brings about a mutator phenotype, which causes a predisposition to cancer.
      But MMR status also affects meiotic and mitotic recombination, DNA-damage
      signalling, apoptosis and cell-type-specific processes such as class-switch
      recombination, somatic hypermutation and triplet-repeat expansion. This article
      reviews our current understanding of this multifaceted DNA-repair system in human
      cells.

PMID- 16612327
TI  - ABC transporter expression profiling after ischemic reperfusion injury in mouse
      kidney.
AB  - Renal ATP binding cassette (ABC) transporters have an important role in the
      elimination of metabolic waste products and compounds foreign to the body. The
      kidney has the ability to tightly control the expression of these efflux
      transporters to maintain homeostasis, and as a major mechanism of adaptation to
      environmental stress. In the present study, we investigated the expression of 45
      ABC transporter genes in the mouse kidney under basal conditions, after induction
      of ischemia and after regeneration. Two days after clamping, mice showed a 76%
      decrease in renal creatinine clearance, which improved clearly within 7 days.
      This was confirmed by histological examinations. Seven days after ischemia, real
      time quantitative Polymerase chain reaction data showed that transcript abundance
      of abcb1, abcb11, and abcc4 was increased, and that of abca3, abcc2, and abcg2
      decreased. Expression of all transporters returned to baseline after 14 days,
      except for abcb11, which was reduced. Abcb11 is the major liver canalicular bile
      salt export pump. Here we show for the first time expression in the kidney and
      localization of the transporter to the apical membrane of proximal tubules. The
      presence of another novel renal transporter, abca3, was confirmed by Western
      blotting. Immunohistochemistry showed that abca3 is localized to the peritubular
      capillaries and apical membrane of proximal tubules. In conclusion, after
      inducing ischemic reperfusion injury in the kidney, ABC transporters appear to be
      differentially regulated, which might be associated with the renal regeneration
      process. Furthermore, we showed for the first time expression and subcellular
      localization of abcb11 and abca3 in mouse kidney.

PMID- 16612328
TI  - Glomerular filtration rate via plasma iohexol disappearance: pilot study for
      chronic kidney disease in children.
AB  - To guide the design of a nation-wide cohort study of chronic kidney disease in
      children, we determined how iohexol plasma disappearance curves could be used in
      children to measure glomerular filtration rate (GFR). Iohexol (5 ml) was
      administered intravenously and blood samples were obtained at 10, 20, 30, 60,
      120, 240, 300, and 360 min after injection (N=29) and assayed by high performance
      liquid chromatography. Four urines were also collected following the injection.
      Intra-assay coefficient of variation (CV) in serum was 1.3% at 100 mg/l, 2.6% at
      15 mg/l, and 3.4% for duplicate unknowns. GFR(9) was computed from iohexol dose
      and area under the nine-point blood disappearance curve, using double exponential
      modeling. Only 2.8% of 254 data points deviated by >3 CV from the curves. GFR(4)
      calculated from 10, 30, 120, and 300 min points correlated well with GFR(9)
      (r=0.999) and showed no bias (means+/-s.d. of GFR(9) and GFR(4)=59.3+/-36.3 and
      59.4+/-36.0 ml/min per 1.73 m(2)). Relationship of GFR(9) and one-compartment GFR
      followed quadratic equation as previously reported by Brochner-Mortensen,
      allowing GFR to be calculated from 120 and 300 min points. This GFR(2) correlated
      well with GFR(9) (r=0.986). Estimated GFR from Schwartz height/creatinine formula
      correlated with GFR(9)(r=0.934) but overestimated GFR by 12.2 ml/min per 1.73
      m(2). Urine iohexol clearance was poorly correlated (r=0.770) with GFR(9) owing
      to variability in urine collections (median CV=24%). GFR can be measured
      accurately using four-point iohexol plasma disappearance (in most cases, two
      points suffice); estimated GFR and urinary clearances are less useful.

PMID- 16612329
TI  - The importance of residual renal function in dialysis patients.
AB  - Preserving residual renal function has always been the primary clinical goal for
      every nephrologist managing patients with chronic kidney disease. There is no
      reason why this important goal should not extend to patients with stage 5 chronic
      kidney disease receiving dialysis. Indeed, there is now clear evidence that
      preserving residual renal function remains important after the commencement of
      dialysis. Residual renal function contributes significantly to the overall health
      and well-being of dialysis patients. It not only provides small solute clearance
      but also plays an important role in maintaining fluid balance, phosphorus
      control, and removal of middle molecular uremic toxins, and shows strong inverse
      relationships with valvular calcification and cardiac hypertrophy in dialysis
      patients. Decline of residual renal function also contributes significantly to
      anemia, inflammation, and malnutrition in patients on dialysis. More importantly,
      the loss of residual renal function, especially in patients on peritoneal
      dialysis, is a powerful predictor of mortality. In addition, there is increasing
      evidence that residual renal and peritoneal dialysis clearance cannot be assumed
      to be equivalent qualitatively, thus indicating the need to preserve residual
      renal function in patients on dialysis. In this article, we will review evidence
      that residual renal function is important in dialysis patients (especially
      peritoneal dialysis) and outline potential strategies that may better preserve
      residual renal function in dialysis patients.

PMID- 16612330
TI  - Prevalence and risk factors for microalbuminuria in a referred cohort of type II
      diabetic patients: a global perspective.
AB  - We described the characteristics in a referred cohort of type II diabetic
      patients in the Developing Education on Microalbuminuria for Awareness of renal
      and cardiovascular risk in Diabetes study evaluating the global prevalence and
      determinants of microalbuminuria (MA). A cross-sectional study evaluating 32,208
      type II diabetic patients without known albuminuria from 33 countries was
      performed. Overall, 8057 patients were excluded, either because of prior known
      proteinuria or non-diabetic nephropathy (3670), or because of invalid urine
      collections (4387). One single random urinary albumin/creatinine ratio was
      obtained in 24,151 patients (75%). The overall global prevalence of normo-, micro
      , and macroalbuminuria was 51, 39, and 10%, respectively. The Asian and Hispanic
      patients had the highest prevalence of a raised urinary albumin/creatinine ratio
      (55%) and Caucasians the lowest (40.6), P<0.0001. HbA1c, systolic blood pressure
      (BP), ethnicity, retinopathy, duration of diabetes, kidney function, body height,
      and smoking were all independent risk factors of MA, P<0.0001. Estimated
      glomerular filtration rate was below 60 ml/min/1.73 m(2) in 22% of the 11,573
      patients with available data. Systolic BP below 130 mmHg was found in 33 and 43%
      had an HbA1c below 7%. The frequency of patients receiving aspirin was 32%,
      statins 29%, and BP-lowering therapy 63%. A high prevalence globally of MA and
      reduced kidney function, both conditions associated with enhanced renal and
      cardiovascular risk, was detected in type II diabetic patients without prior
      known nephropathy. Early detection, monitoring of vascular complications, and
      more aggressive multifactorial treatment aiming at renal and vascular protection
      are urgently needed.

PMID- 16612331
TI  - Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells.
AB  - Vascular smooth muscle cell (VSMC) proliferation is a key event in the
      progression of arteriosclerosis. Clinical studies show that uremic toxins
      deteriorate the arteriosclerosis in renal failure patients. Indoxyl sulfate (IS)
      is a strong protein-bound uremic toxin, but the effect of IS on VSMC
      proliferation has not been studied. We examined the effect of IS on rat VSMC
      proliferation, assessed by a cell counting kit (4-[3-[4-lodophenyl]-2-4(4
      nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] assay) and by
      [(3)H]thymidine incorporation in vitro. We further evaluated a contribution of
      mitogen-activated protein kinase (MAPK; p44/42 MAPK) to VSMC proliferation by IS.
      Immunohistochemical staining was performed for VSMCs using antirat organic anion
      transporter (OAT)3 antibody. The mRNA expressions of platelet-derived growth
      factor (PDGF)-A and -C chains, and PDGF-beta receptor were evaluated by real-time
      PCR. IS stimulated the proliferation of VSMCs in a concentration-dependent manner
      and activated p44/42 MAPK. Concentration of IS needed to stimulate the
      proliferation of rat VSMC was about 250 microM, which is compatible with that in
      the serum of end-stage renal failure patients. PD98059 (10 microM), a selective
      inhibitor of MAPK/extracellular signal-regulated kinase, inhibited the IS-induced
      (250 microM) VSMC proliferation and phosphorylation of MAPK. Probenecid (0.5 mM),
      an inhibitor and substrate of OAT, inhibited the IS-induced (250 microM) VSMC
      proliferation. Rat OAT3 was detected in VSMCs. The mRNA expressions of PDGF-C
      chain and PDGF-beta receptor were significantly increased by IS. We conclude that
      IS directly stimulates rat VSMC proliferation and activates MAPK in vitro. This
      might be one of the mechanisms underlying the progression of atherosclerotic
      lesions in end-stage renal disease patients.

PMID- 16612332
TI  - TGF-beta1 mRNA upregulation influences chronic renal allograft dysfunction.
AB  - Acute rejection (AR) is a dominant risk factor for developing chronic allograft
      nephropathy (CAN) after kidney transplantation. CAN is characterized by
      progressive interstitial fibrosis. It has been associated with increased
      transforming growth factor (TGF)-beta1 expression, however, kinetic studies are
      absent. We investigated whether intragraft TGF-beta1 expression in various causes
      of early graft dysfunction may influence late renal allograft dysfunction. A
      total of 174 human renal biopsies were quantified for TGF-beta1 mRNA expression
      using real-time reverse transcriptase-polymerase chain reaction. Expression
      levels were correlated with the Banff histopathological grades, TGF-beta1
      immunohistology, and clinical follow-up. TGF-beta1 was most markedly upregulated
      in AR, CAN, and acute tubular necrosis - delayed graft function compared to non
      rejecting controls (P < 0.001). TGF-beta1 expression was heightened in borderline
      changes (P < 0.01), recurrence of glomerulonephritis, and cyclosporine toxicity
      (P < 0.05). There was no correlation between intragraft TGF-beta1 expression
      during AR and short-term outcome of a rejection episode. TGF-beta1 gene
      overexpression during CAN has been shown to be associated with the increased risk
      for renal allograft dysfunction 18 months after biopsy (odds ratios 9.9 vs 3.2,
      respectively). Intragraft TGF-beta1 mRNA expression is significantly upregulated
      in both AR and CAN. Thus, our results support the hypothesis that TGF-beta1 might
      play a key role in chronic allograft dysfunction.

PMID- 16612333
TI  - The influence of CYP3A gene polymorphisms on cyclosporine dose requirement in
      renal allograft recipients.
AB  - Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes
      and characterized by a narrow therapeutic range with wide interindividual
      variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in
      CYP3A genes have been shown to correlate significantly with the CYP3A protein
      expression and activity. We therefore postulated that these polymorphisms could
      be responsible for some of the interindividual variation in cyclosporine
      pharmacokinetics. The objective of our study is to determine correlation if any
      between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine
      dose requirement and concentration-to-dose ratio in renal allograft recipients.
      Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5
      A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the
      corresponding cyclosporine trough levels for each patient were recorded so that
      cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D,
      whereby C(0) is trough level and D is daily dose per weight) could be calculated.
      A total of 67 patients were recruited for our study. The dose requirement for 1,
      3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2
      mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked
      genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3
      (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post
      transplantation (P < 0.016). The identification of patients with *1*1*1*1 by
      CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive
      impact on patient outcome with reduced rejection rate by providing pretransplant
      pharmacogenetic information for optimization of cyclosporine A dosing.

PMID- 16612334
TI  - Osteoporosis in hemodialysis patients revisited by bone histomorphometry: a new
      insight into an old problem.
AB  - Osteoporosis in hemodialysis patients is associated with high morbidity and
      mortality and, although extensively studied by noninvasive methods, has never
      been assessed through bone biopsy. The aim of this study was to use
      histomorphometry to evaluate osteoporosis and identify factors related to its
      development in hemodialysis patients. We conducted a cross-sectional study
      involving 98 patients (35 women and 63 men; mean age: 48.4 +/- 13 years) on
      hemodialysis for 36.9 +/- 24.7 months. Patients were submitted to transiliac bone
      biopsy with double tetracycline labeling. The bone metabolism factors ionized
      calcium, phosphorus, bone alkaline phosphatase, deoxypyridinoline, intact
      parathyroid hormone, and 25(OH) vitamin D were evaluated, as were the bone
      remodeling cytokines osteoprotegerin (OPG), soluble receptor-activator of NF
      kappabeta ligand (sRANKL) and tumor necrosis factor-alpha (TNF)alpha.
      Osteoporosis was defined as trabecular bone volume (BV/TV) greater than 1 s.d.
      below normal (men <17.4%; women <14.7%). Forty-five patients (46%) presented
      osteoporosis, which was correlated with white race. We found BV/TV to correlate
      with age, OPG/sRANKL ratio, TNFalpha levels, and length of amenorrhea. In
      multiple regression analysis adjusted for sex and age, length of amenorrhea,
      white race, and OPG/sRANKL ratio were independent determinants of BV/TV.
      Histomorphometric analysis demonstrated that osteoporotic patients presented
      normal eroded surface and low bone formation rate (BFR/BS). Osteoporosis is
      prevalent in hemodialysis patients. Low BFR/BS could be involved in its
      development, even when bone resorption is normal. Cytokines may also play a role
      as may traditional risk factors such as advanced age, hypogonadism, and white
      race.

PMID- 16612335
TI  - Deletion of Lys224 in regulatory domain 4 of Factor H reveals a novel
      pathomechanism for dense deposit disease (MPGN II).
AB  - We report a novel pathomechanism for membranoproliferative glomerulonephritis
      type II (MPGN II) caused by a mutant Factor H protein expressed in the plasma.
      Genetic analyses of two patients revealed deletion of a single Lys residue (K224)
      located within the complement regulatory region in domain 4 of Factor H. This
      deletion resulted in defective complement control: mutant protein purified from
      the plasma of patients showed severely reduced cofactor and decay-accelerating
      activity, as well as reduced binding to the central complement component C3b.
      However, cell-binding activity of the mutant protein was normal and comparable to
      wild-type Factor H. The patients are daughters of consanguineous parents. As both
      patients but also their healthy mother were positive for C3 nephritic factor, the
      mutant Factor H protein is considered relevant for unrestricted activation of the
      disease-causing activation of the alternative complement pathway. Replacement of
      functional Factor H by fresh frozen plasma (10-15 ml/kg/14 days) was well
      tolerated, prevented so far disease progression in both patients, and is in the
      long run expected to preserve kidney function.

PMID- 16612340
TI  - More than the money.

PMID- 16612336
TI  - Taxonomy: Sus bucculentus revisited.
AB  - In 1997, the rediscovery of Sus bucculentus in Laos was announced by Groves et
      al.--this wild pig species had gone unrecorded since first being described in
      1892. Although the identification of the new specimen was based initially on
      morphology, the authors also used a 7% sequence divergence from the common
      Eurasian pig S. scrofa (based on their analysis of 327 base pairs of the gene
      encoding mitochondrial 12S ribosomal RNA) as support for the species status of S.
      bucculentus. Concerned about the large divergence reported for a relatively
      conserved gene, and the absence of the sequence in any public database, we
      analysed an additional tissue sample from the specimen and found only 0.6%
      divergence from S. scrofa. Our more extensive analysis places the sample within
      the S. scrofa clade, calling into question the species status of S. bucculentus
      and demonstrating the need for both phylogenetic and morphological evidence in
      defining species.

PMID- 16612342
TI  - Neglected neighbour.

PMID- 16612341
TI  - The constant gardeners.

PMID- 16612344
TI  - Patients warned about unproven spinal surgery.

PMID- 16612345
TI  - Bird-flu experts question advice on eating poultry.

PMID- 16612346
TI  - Malaria breakthrough raises spectre of drug resistance.

PMID- 16612348
TI  - Two telescopes join hunt for ET.

PMID- 16612349
TI  - Can super-antibody drugs be tamed?

PMID- 16612350
TI  - Japan revises its military plans for space.

PMID- 16612352
TI  - Plant science: gardens in full bloom.

PMID- 16612353
TI  - Seismology: breaking new ground.

PMID- 16612354
TI  - University challenge.

PMID- 16612355
TI  - Local people may be the best allies in conservation.

PMID- 16612356
TI  - Risks of a high-protein diet outweigh the benefits.

PMID- 16612357
TI  - Industry: speak up to stop its pressure on academia.

PMID- 16612358
TI  - Industry: policing the 'dark side' of ecology.

PMID- 16612364
TI  - Astrophysics: a whirling dervish.

PMID- 16612365
TI  - Ageing: chromatin unbound.

PMID- 16612366
TI  - Conservation biology: roads and genetic connectivity.

PMID- 16612367
TI  - Chemistry: a nose for sarin.

PMID- 16612368
TI  - Quantum physics: equilibrium on hold.

PMID- 16612369
TI  - Biogeochemistry: methane and microbes.

PMID- 16612370
TI  - Biological imaging: the diffraction barrier broken.

PMID- 16612371
TI  - Behavioural ecology: grasshoppers don't play possum.

PMID- 16612372
TI  - Evolution: a catfish that can strike its prey on land.
AB  - An important step towards understanding the evolution of terrestriality in
      vertebrates is to identify how the aquatic ancestors of tetrapods were able to
      access ground-based prey. We have discovered that the 'eel catfish' Channallabes
      apus, an inhabitant of the muddy swamps of tropical Africa, has a remarkable
      ability to forage and capture prey on land. The animal's capacity to bend its
      head down towards the ground while feeding seems to be an essential feature that
      may have enabled fish to make the transition from an aquatic to a terrestrial
      mode.

PMID- 16612373
TI  - Asa Issie, Aramis and the origin of Australopithecus.
AB  - The origin of Australopithecus, the genus widely interpreted as ancestral to
      Homo, is a central problem in human evolutionary studies. Australopithecus
      species differ markedly from extant African apes and candidate ancestral hominids
      such as Ardipithecus, Orrorin and Sahelanthropus. The earliest described
      Australopithecus species is Au. anamensis, the probable chronospecies ancestor of
      Au. afarensis. Here we describe newly discovered fossils from the Middle Awash
      study area that extend the known Au. anamensis range into northeastern Ethiopia.
      The new fossils are from chronometrically controlled stratigraphic sequences and
      date to about 4.1-4.2 million years ago. They include diagnostic craniodental
      remains, the largest hominid canine yet recovered, and the earliest
      Australopithecus femur. These new fossils are sampled from a woodland context.
      Temporal and anatomical intermediacy between Ar. ramidus and Au. afarensis
      suggest a relatively rapid shift from Ardipithecus to Australopithecus in this
      region of Africa, involving either replacement or accelerated phyletic evolution.

PMID- 16612374
TI  - Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell
      dendritic cell interaction.
AB  - CD8+ T cells have a crucial role in resistance to pathogens and can kill
      malignant cells; however, some critical functions of these lymphocytes depend on
      helper activity provided by a distinct population of CD4+ T cells. Cooperation
      between these lymphocyte subsets involves recognition of antigens co-presented by
      the same dendritic cell, but the frequencies of such antigen-bearing cells early
      in an infection and of the relevant naive T cells are both low. This suggests
      that an active mechanism facilitates the necessary cell-cell associations. Here
      we demonstrate that after immunization but before antigen recognition, naive CD8+
      T cells in immunogen-draining lymph nodes upregulate the chemokine receptor CCR5,
      permitting these cells to be attracted to sites of antigen-specific dendritic
      cell-CD4+ T cell interaction where the cognate chemokines CCL3 and CCL4 (also
      known as MIP-1alpha and MIP-1beta) are produced. Interference with this actively
      guided recruitment markedly reduces the ability of CD4+ T cells to promote memory
      CD8+ T-cell generation, indicating that an orchestrated series of differentiation
      events drives nonrandom cell-cell interactions within lymph nodes, optimizing
      CD8+ T-cell immune responses involving the few antigen-specific precursors
      present in the naive repertoire.

PMID- 16612375
TI  - Vega is a rapidly rotating star.
AB  - Vega, the second brightest star in the northern hemisphere, serves as a primary
      spectral type standard. Although its spectrum is dominated by broad hydrogen
      lines, the narrower lines of the heavy elements suggested slow to moderate
      rotation, giving confidence that the ground-based calibration of its visible
      spectrum could be safely extrapolated into the ultraviolet and near-infrared
      (through atmosphere models), where it also serves as the primary photometric
      calibrator. But there have been problems: the star is too bright compared to its
      peers and it has unusually shaped absorption line profiles, leading some to
      suggest that it is a distorted, rapidly rotating star seen pole-on. Here we
      report optical interferometric observations that show that Vega has the
      asymmetric brightness distribution of the bright, slightly offset polar axis of a
      star rotating at 93 per cent of its breakup speed. In addition to explaining the
      unusual brightness and line shape peculiarities, this result leads to the
      prediction of an excess of near-infrared emission compared to the visible, in
      agreement with observations. The large temperature differences predicted across
      its surface call into question composition determinations, adding uncertainty to
      Vega's age and opening the possibility that its debris disk could be
      substantially older than previously thought.

PMID- 16612376
TI  - A quantum Newton's cradle.
AB  - It is a fundamental assumption of statistical mechanics that a closed system with
      many degrees of freedom ergodically samples all equal energy points in phase
      space. To understand the limits of this assumption, it is important to find and
      study systems that are not ergodic, and thus do not reach thermal equilibrium. A
      few complex systems have been proposed that are expected not to thermalize
      because their dynamics are integrable. Some nearly integrable systems of many
      particles have been studied numerically, and shown not to ergodically sample
      phase space. However, there has been no experimental demonstration of such a
      system with many degrees of freedom that does not approach thermal equilibrium.
      Here we report the preparation of out-of-equilibrium arrays of trapped one
      dimensional (1D) Bose gases, each containing from 40 to 250 (87)Rb atoms, which
      do not noticeably equilibrate even after thousands of collisions. Our results are
      probably explainable by the well-known fact that a homogeneous 1D Bose gas with
      point-like collisional interactions is integrable. Until now, however, the time
      evolution of out-of-equilibrium 1D Bose gases has been a theoretically unsettled
      issue, as practical factors such as harmonic trapping and imperfectly point-like
      interactions may compromise integrability. The absence of damping in 1D Bose
      gases may lead to potential applications in force sensing and atom
      interferometry.

PMID- 16612377
TI  - Parametric oscillation in vertical triple microcavities.
AB  - Optical parametric oscillation is a nonlinear process that enables coherent
      generation of 'signal' and 'idler' waves, shifted in frequency from the pump
      wave. Efficient parametric conversion is the paradigm for the generation of twin
      or entangled photons for quantum optics applications such as quantum
      cryptography, or for the generation of new frequencies in spectral domains not
      accessible by existing devices. Rapid development in the field of quantum
      information requires monolithic, alignment-free sources that enable efficient
      coupling into optical fibres and possibly electrical injection. During the past
      decade, much effort has been devoted to the development of integrated devices for
      quantum information and to the realization of all-semiconductor parametric
      oscillators. Nevertheless, at present optical parametric oscillators typically
      rely on nonlinear crystals placed into complex external cavities, and pumped by
      powerful external lasers. Long interaction lengths are typically required and the
      phase mismatch between the parametric waves propagating at different velocities
      results in poor parametric conversion efficiencies. Here we report the
      demonstration of parametric oscillation in a monolithic semiconductor triple
      microcavity with signal, pump and idler waves propagating along the vertical
      direction of the nanostructure. Alternatively, signal and idler beams can also be
      collected at finite angles, allowing the generation of entangled photon pairs.
      The pump threshold intensity is low enough to envisage the realization of an all
      semiconductor electrically pumped micro-parametric oscillator.

PMID- 16612378
TI  - Management of singlet and triplet excitons for efficient white organic light
      emitting devices.
AB  - Lighting accounts for approximately 22 per cent of the electricity consumed in
      buildings in the United States, with 40 per cent of that amount consumed by
      inefficient (approximately 15 lm W(-1)) incandescent lamps. This has generated
      increased interest in the use of white electroluminescent organic light-emitting
      devices, owing to their potential for significantly improved efficiency over
      incandescent sources combined with low-cost, high-throughput manufacturability.
      The most impressive characteristics of such devices reported to date have been
      achieved in all-phosphor-doped devices, which have the potential for 100 per cent
      internal quantum efficiency: the phosphorescent molecules harness the triplet
      excitons that constitute three-quarters of the bound electron-hole pairs that
      form during charge injection, and which (unlike the remaining singlet excitons)
      would otherwise recombine non-radiatively. Here we introduce a different device
      concept that exploits a blue fluorescent molecule in exchange for a
      phosphorescent dopant, in combination with green and red phosphor dopants, to
      yield high power efficiency and stable colour balance, while maintaining the
      potential for unity internal quantum efficiency. Two distinct modes of energy
      transfer within this device serve to channel nearly all of the triplet energy to
      the phosphorescent dopants, retaining the singlet energy exclusively on the blue
      fluorescent dopant. Additionally, eliminating the exchange energy loss to the
      blue fluorophore allows for roughly 20 per cent increased power efficiency
      compared to a fully phosphorescent device. Our device challenges incandescent
      sources by exhibiting total external quantum and power efficiencies that peak at
      18.7 +/- 0.5 per cent and 37.6 +/- 0.6 lm W(-1), respectively, decreasing to 18.4
      +/- 0.5 per cent and 23.8 +/- 0.5 lm W(-1) at a high luminance of 500 cd m(-2).

PMID- 16612379
TI  - Deep origin and hot melting of an Archaean orogenic peridotite massif in Norway.
AB  - The buoyancy and strength of sub-continental lithospheric mantle is thought to
      protect the oldest continental crust (cratons) from destruction by plate tectonic
      processes. The exact origin of the lithosphere below cratons is controversial,
      but seems clearly to be a residue remaining after the extraction of large amounts
      of melt. Models to explain highly melt-depleted but garnet-bearing rock
      compositions require multi-stage processes with garnet and clinopyroxene possibly
      of secondary origin. Here we report on orogenic peridotites (fragments of
      cratonic mantle incorporated into the crust during continent-continent plate
      collision) from Otroy, western Norway. We show that the peridotites underwent
      extensive melting during upwelling from depths of 350 kilometres or more, forming
      a garnet-bearing cratonic root in a single melting event. These peridotites
      appear to be the residue after Archaean aluminium depleted komatiite magmatism.

PMID- 16612380
TI  - A microbial consortium couples anaerobic methane oxidation to denitrification.
AB  - Modern agriculture has accelerated biological methane and nitrogen cycling on a
      global scale. Freshwater sediments often receive increased downward fluxes of
      nitrate from agricultural runoff and upward fluxes of methane generated by
      anaerobic decomposition. In theory, prokaryotes should be capable of using
      nitrate to oxidize methane anaerobically, but such organisms have neither been
      observed in nature nor isolated in the laboratory. Microbial oxidation of methane
      is thus believed to proceed only with oxygen or sulphate. Here we show that the
      direct, anaerobic oxidation of methane coupled to denitrification of nitrate is
      possible. A microbial consortium, enriched from anoxic sediments, oxidized
      methane to carbon dioxide coupled to denitrification in the complete absence of
      oxygen. This consortium consisted of two microorganisms, a bacterium representing
      a phylum without any cultured species and an archaeon distantly related to marine
      methanotrophic Archaea. The detection of relatives of these prokaryotes in
      different freshwater ecosystems worldwide indicates that the reaction presented
      here may make a substantial contribution to biological methane and nitrogen
      cycles.

PMID- 16612381
TI  - Nitrogen limitation constrains sustainability of ecosystem response to CO2.
AB  - Enhanced plant biomass accumulation in response to elevated atmospheric CO2
      concentration could dampen the future rate of increase in CO2 levels and
      associated climate warming. However, it is unknown whether CO2-induced
      stimulation of plant growth and biomass accumulation will be sustained or whether
      limited nitrogen (N) availability constrains greater plant growth in a CO2
      enriched world. Here we show, after a six-year field study of perennial grassland
      species grown under ambient and elevated levels of CO2 and N, that low
      availability of N progressively suppresses the positive response of plant biomass
      to elevated CO2. Initially, the stimulation of total plant biomass by elevated
      CO2 was no greater at enriched than at ambient N supply. After four to six years,
      however, elevated CO2 stimulated plant biomass much less under ambient than
      enriched N supply. This response was consistent with the temporally divergent
      effects of elevated CO2 on soil and plant N dynamics at differing levels of N
      supply. Our results indicate that variability in availability of soil N and
      deposition of atmospheric N are both likely to influence the response of plant
      biomass accumulation to elevated atmospheric CO2. Given that limitations to
      productivity resulting from the insufficient availability of N are widespread in
      both unmanaged and managed vegetation, soil N supply is probably an important
      constraint on global terrestrial responses to elevated CO2.

PMID- 16612382
TI  - Parental investment by skin feeding in a caecilian amphibian.
AB  - Although the initial growth and development of most multicellular animals depends
      on the provision of yolk, there are many varied contrivances by which animals
      provide additional or alternative investment in their offspring. Providing
      offspring with additional nutrition should be favoured by natural selection when
      the consequent increased fitness of the young offsets any corresponding reduction
      in fecundity. Alternative forms of nutrition may allow parents to delay and
      potentially redirect their investment. Here we report a remarkable form of
      parental care and mechanism of parent-offspring nutrient transfer in a caecilian
      amphibian. Boulengerula taitanus is a direct-developing, oviparous caecilian, the
      skin of which is transformed in brooding females to provide a rich supply of
      nutrients for the developing offspring. Young animals are equipped with a
      specialized dentition, which they use to peel and eat the outer layer of their
      mother's modified skin. This new form of parental care provides a plausible
      intermediate stage in the evolution of viviparity in caecilians. At independence,
      offspring of viviparous and of oviparous dermatotrophic caecilians are relatively
      large despite being provided with relatively little yolk. The specialized
      dentition of skin-feeding (dermatophagous) caecilians may constitute a
      preadaptation to the fetal feeding on the oviduct lining of viviparous
      caecilians.

PMID- 16612383
TI  - Independent evolution of bitter-taste sensitivity in humans and chimpanzees.
AB  - It was reported over 65 years ago that chimpanzees, like humans, vary in taste
      sensitivity to the bitter compound phenylthiocarbamide (PTC). This was suggested
      to be the result of a shared balanced polymorphism, defining the first, and now
      classic, example of the effects of balancing selection in great apes. In humans,
      variable PTC sensitivity is largely controlled by the segregation of two common
      alleles at the TAS2R38 locus, which encode receptor variants with different
      ligand affinities. Here we show that PTC taste sensitivity in chimpanzees is also
      controlled by two common alleles of TAS2R38; however, neither of these alleles is
      shared with humans. Instead, a mutation of the initiation codon results in the
      use of an alternative downstream start codon and production of a truncated
      receptor variant that fails to respond to PTC in vitro. Association testing of
      PTC sensitivity in a cohort of captive chimpanzees confirmed that chimpanzee
      TAS2R38 genotype accurately predicts taster status in vivo. Therefore, although
      Fisher et al.'s observations were accurate, their explanation was wrong. Humans
      and chimpanzees share variable taste sensitivity to bitter compounds mediated by
      PTC receptor variants, but the molecular basis of this variation has arisen
      twice, independently, in the two species.

PMID- 16612384
TI  - STED microscopy reveals that synaptotagmin remains clustered after synaptic
      vesicle exocytosis.
AB  - Synaptic transmission is mediated by neurotransmitters that are stored in
      synaptic vesicles and released by exocytosis upon activation. The vesicle
      membrane is then retrieved by endocytosis, and synaptic vesicles are regenerated
      and re-filled with neurotransmitter. Although many aspects of vesicle recycling
      are understood, the fate of the vesicles after fusion is still unclear. Do their
      components diffuse on the plasma membrane, or do they remain together? This
      question has been difficult to answer because synaptic vesicles are too small
      (approximately 40 nm in diameter) and too densely packed to be resolved by
      available fluorescence microscopes. Here we use stimulated emission depletion
      (STED) to reduce the focal spot area by about an order of magnitude below the
      diffraction limit, thereby resolving individual vesicles in the synapse. We show
      that synaptotagmin I, a protein resident in the vesicle membrane, remains
      clustered in isolated patches on the presynaptic membrane regardless of whether
      the nerve terminals are mildly active or intensely stimulated. This suggests that
      at least some vesicle constituents remain together during recycling. Our study
      also demonstrates that questions involving cellular structures with dimensions of
      a few tens of nanometres can be resolved with conventional far-field optics and
      visible light.

PMID- 16612385
TI  - Production of the antimalarial drug precursor artemisinic acid in engineered
      yeast.
AB  - Malaria is a global health problem that threatens 300-500 million people and
      kills more than one million people annually. Disease control is hampered by the
      occurrence of multi-drug-resistant strains of the malaria parasite Plasmodium
      falciparum. Synthetic antimalarial drugs and malarial vaccines are currently
      being developed, but their efficacy against malaria awaits rigorous clinical
      testing. Artemisinin, a sesquiterpene lactone endoperoxide extracted from
      Artemisia annua L (family Asteraceae; commonly known as sweet wormwood), is
      highly effective against multi-drug-resistant Plasmodium spp., but is in short
      supply and unaffordable to most malaria sufferers. Although total synthesis of
      artemisinin is difficult and costly, the semi-synthesis of artemisinin or any
      derivative from microbially sourced artemisinic acid, its immediate precursor,
      could be a cost-effective, environmentally friendly, high-quality and reliable
      source of artemisinin. Here we report the engineering of Saccharomyces cerevisiae
      to produce high titres (up to 100 mg l(-1)) of artemisinic acid using an
      engineered mevalonate pathway, amorphadiene synthase, and a novel cytochrome P450
      monooxygenase (CYP71AV1) from A. annua that performs a three-step oxidation of
      amorpha-4,11-diene to artemisinic acid. The synthesized artemisinic acid is
      transported out and retained on the outside of the engineered yeast, meaning that
      a simple and inexpensive purification process can be used to obtain the desired
      product. Although the engineered yeast is already capable of producing
      artemisinic acid at a significantly higher specific productivity than A. annua,
      yield optimization and industrial scale-up will be required to raise artemisinic
      acid production to a level high enough to reduce artemisinin combination
      therapies to significantly below their current prices.

PMID- 16612386
TI  - Reactive oxygen species have a causal role in multiple forms of insulin
      resistance.
AB  - Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic
      of a wide range of other clinical and experimental settings. Little is known
      about why insulin resistance occurs in so many contexts. Do the various insults
      that trigger insulin resistance act through a common mechanism? Or, as has been
      suggested, do they use distinct cellular pathways? Here we report a genomic
      analysis of two cellular models of insulin resistance, one induced by treatment
      with the cytokine tumour-necrosis factor-alpha and the other with the
      glucocorticoid dexamethasone. Gene expression analysis suggests that reactive
      oxygen species (ROS) levels are increased in both models, and we confirmed this
      through measures of cellular redox state. ROS have previously been proposed to be
      involved in insulin resistance, although evidence for a causal role has been
      scant. We tested this hypothesis in cell culture using six treatments designed to
      alter ROS levels, including two small molecules and four transgenes; all
      ameliorated insulin resistance to varying degrees. One of these treatments was
      tested in obese, insulin-resistant mice and was shown to improve insulin
      sensitivity and glucose homeostasis. Together, our findings suggest that
      increased ROS levels are an important trigger for insulin resistance in numerous
      settings.

PMID- 16612387
TI  - IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll
      like receptors 7 and 9.
AB  - The Toll-like receptor (TLR) family has important roles in microbial recognition
      and dendritic cell activation. TLRs 7 and 9 can recognize nucleic acids and
      trigger signalling cascades that activate plasmacytoid dendritic cells to produce
      interferon-alpha (IFN-alpha) (refs 7, 8). TLR7/9-mediated dendritic cell
      activation is critical for antiviral immunity but also contributes to the
      pathogenesis of systemic lupus erythematosus, a disease in which serum IFN-alpha
      levels are elevated owing to plasmacytoid dendritic cell activation. TLR7/9
      induced IFN-alpha induction depends on a molecular complex that contains a TLR
      adaptor, MyD88, and IFN regulatory factor 7 (IRF-7) (refs 10-14), but the
      underlying molecular mechanisms are as yet unknown. Here we show that IkappaB
      kinase-alpha (IKK-alpha) is critically involved in TLR7/9-induced IFN-alpha
      production. TLR7/9-induced IFN-alpha production was severely impaired in IKK
      alpha-deficient plasmacytoid dendritic cells, whereas inflammatory cytokine
      induction was decreased but still occurred. Kinase-deficient IKK-alpha inhibited
      the ability of MyD88 to activate the Ifna promoter in synergy with IRF-7.
      Furthermore, IKK-alpha associated with and phosphorylated IRF-7. Our results
      identify a role for IKK-alpha in TLR7/9 signalling, and highlight IKK-alpha as a
      potential target for manipulating TLR-induced IFN-alpha production.

PMID- 16612388
TI  - The reversibility of mitotic exit in vertebrate cells.
AB  - A guiding hypothesis for cell-cycle regulation asserts that regulated proteolysis
      constrains the directionality of certain cell-cycle transitions. Here we test
      this hypothesis for mitotic exit, which is regulated by degradation of the cyclin
      dependent kinase 1 (Cdk1) activator, cyclin B. Application of chemical Cdk1
      inhibitors to cells in mitosis induces cytokinesis and other normal aspects of
      mitotic exit, including cyclin B degradation. However, chromatid segregation
      fails, resulting in entrapment of chromatin in the midbody. If cyclin B
      degradation is blocked with a proteasome inhibitor or by expression of non
      degradable cyclin B, Cdk inhibitors will nonetheless induce mitotic exit and
      cytokinesis. However, if after mitotic exit, the Cdk1 inhibitor is washed free
      from cells in which cyclin B degradation is blocked, the cells can revert back to
      M phase. This reversal is characterized by chromosome recondensation, nuclear
      envelope breakdown, assembly of microtubules into a mitotic spindle, and in most
      cases, dissolution of the midbody, reopening of the cleavage furrow, and
      realignment of chromosomes at the metaphase plate. These findings demonstrate
      that proteasome-dependent degradation of cyclin B provides directionality for the
      M phase to G1 transition.

PMID- 16612389
TI  - Toxin-induced conformational changes in a potassium channel revealed by solid
      state NMR.
AB  - The active site of potassium (K+) channels catalyses the transport of K+ ions
      across the plasma membrane--similar to the catalytic function of the active site
      of an enzyme--and is inhibited by toxins from scorpion venom. On the basis of the
      conserved structures of K+ pore regions and scorpion toxins, detailed structures
      for the K+ channel-scorpion toxin binding interface have been proposed. In these
      models and in previous solution-state nuclear magnetic resonance (NMR) studies
      using detergent-solubilized membrane proteins, scorpion toxins were docked to the
      extracellular entrance of the K+ channel pore assuming rigid, preformed binding
      sites. Using high-resolution solid-state NMR spectroscopy, here we show that high
      affinity binding of the scorpion toxin kaliotoxin to a chimaeric K+ channel (KcsA
      Kv1.3) is associated with significant structural rearrangements in both
      molecules. Our approach involves a combined analysis of chemical shifts and
      proton-proton distances and demonstrates that solid-state NMR is a sensitive
      method for analysing the structure of a membrane protein-inhibitor complex. We
      propose that structural flexibility of the K+ channel and the toxin represents an
      important determinant for the high specificity of toxin-K+ channel interactions.

PMID- 16612391
TI  - Fgf21 is essential for haematopoiesis in zebrafish.
AB  - Fibroblast growth factors (Fgfs) function as key secreted signalling molecules in
      many developmental events. The zebrafish is a powerful model system for the
      investigation of embryonic vertebrate haematopoiesis. Although the effects of Fgf
      signalling on haematopoiesis in vitro have been reported, the functions of Fgf
      signalling in haematopoiesis in vivo remain to be explained. We identified Fgf21
      in zebrafish embryos. Fgf21-knockdown zebrafish embryos lacked erythroid and
      myeloid cells but not blood vessels and lymphoid cells. The knockdown embryos had
      haemangioblasts and haematopoietic stem cells. However, the knockdown embryos had
      significantly fewer myeloid and erythroid progenitor cells. In contrast, Fgf21
      had no significant effect on cell proliferation and apoptosis in the intermediate
      cell mass. These results indicate that Fgf21 is a newly identified factor
      essential for the determination of myelo-erythroid progenitor cell fate in vivo.

PMID- 16612392
TI  - Endosomal hyperacidification in cystic fibrosis is due to defective nitric oxide
      cylic GMP signalling cascade.
AB  - Endosomal hyperacidification in cystic fibrosis (CF) respiratory epithelial cells
      is secondary to a loss of sodium transport control owing to a defective form of
      the CF transmembrane conductance regulator CFTR. Here, we show that endosomal
      hyperacidification can be corrected by activating the signalling cascade
      controlling sodium channels through cyclic GMP. Nitric oxide (NO) donors
      corrected the endosomal hyperacidification in CF cells. Stimulation of CF cells
      with guanylate cyclase agonists corrected the pH in endosomes. Exposure of CF
      cells to an inhibitor of cGMP-specific phosphodiesterase PDE5, Sildenafil,
      normalized the endosomal pH. Treatment with Sildenafil reduced secretion by CF
      cells of the proinflammatory chemokine interleukin 8 following stimulation with
      Pseudomonas aeruginosa products. Thus, the endosomal hyperacidification and
      excessive proinflammatory response in CF are in part due to deficiencies in NO-
      and cGMP-regulated processes and can be pharmacologically reversed using PDE5
      inhibitors.

PMID- 16612393
TI  - Proceeding of the Contrast-Induced Nephropathy Consensus Panel, 17 September
      2005, Paris, France.

PMID- 16612394
TI  - Contrast-induced nephropathy: definition, epidemiology, and patients at risk.
AB  - Radiological procedures utilizing intravascular iodinated contrast media
      injections are being widely applied for both diagnostic and therapeutic purposes.
      This has resulted in an increasing incidence of procedure-related contrast
      induced nephropathy (CIN). The definition of CIN includes absolute (> or = 0.5
      mg/dl) or relative increase (> or = 25%) in serum creatinine at 48-72 h after
      exposure to a contrast agent compared to baseline serum creatinine values, when
      alternative explanations for renal impairment have been excluded. Although the
      risk of renal function impairment associated with radiological procedures is low
      (0.6-2.3%) in the general population, it may be very high in selected patient
      subsets (up to 20%), especially in patients with underlying cardiovascular
      disease. This review provides information on the known risk factors for the
      development of CIN, and completes with describing user-friendly CIN risk score
      based on the readily available information.

PMID- 16612395
TI  - Prevention of contrast-induced nephropathy with volume supplementation.
AB  - Volume supplementation remains the cornerstone for the prevention of contrast
      induced nephropathy (CIN). Current evidence suggests that the combination of
      intravenous and oral volume supplementation effectively prevents CIN in low- and
      moderate-risk patients. Normal isotonic (0.9%) saline should be started 12 h
      before (or at least in the morning of) the contrast procedure with an infusion
      rate of 1 ml/kg of body weight per hour and be continued for 24 h. In addition,
      patients should be encouraged to drink plenty of fluids (tea, mineral water). The
      use of bicarbonate infusion may allow shorter volume supplementation periods.
      Combined intravenous and oral volume supplementation protocols feasible for
      outpatients who limit the intravenous infusion to the contrast procedure are
      under investigation. Future studies are necessary to define further details
      regarding the optimal use of volume supplementation.

PMID- 16612396
TI  - Concomitant drugs with exposure to contrast media.
AB  - The increasing number of radiological procedures performed in old patients with
      high co-morbidity may be one of the problems physicians have to deal with when
      regarding the increasing number of acute renal failures. A key question when
      addressing the patients scheduled to receive iodinated contrast media (CM) is
      which concomitant medications prescribed to the patient are potentially harmful
      or helpful in terms of the risk of contrast-induced nephropathy. This overview
      summarizes the knowledge of concomitant medications in the setting of CM
      application and gives suggestion for prescription. In general, due to the unique
      (yet not fully understood and of high complexity) mechanism of renal damage
      proposed for a variety of nephrotoxic drugs including CM, physicians should
      carefully monitor patients' renal function and hydration status whenever
      concomitant nephrototoxic drugs are used. Recommendations are to monitor kidney
      function with more sensitive measurements of glomerular filtration rate (i.e.
      cystatin C).

PMID- 16612397
TI  - Dialysis and iodinated contrast media.
AB  - Contrast media are excreted mainly by glomerular filtration. There is thus, a
      significant correlation between both body and renal clearances of contrast media
      and glomerular filtration rate, and their renal excretion will be delayed in
      patients with renal insufficiency. Contrast media can be efficiently removed from
      blood by hemodialysis (HD). Since most contrast media are middle-sized molecules,
      the main factors potentially influencing their removal by HD are blood flow,
      membrane surface area, molecular size, transmembrane pressure, and dialysis time.
      Peritoneal dialysis is also effective in removing contrast agents from the body
      but takes longer than HD. Dialysis immediately after radiographic contrast
      studies has been suggested for two groups of patients. Those on chronic HD and
      those at very high risk for contrast nephropathy. Three studies have examined the
      necessity of immediate dialysis after intravascular injection of contrast media
      in chronic HD patients; the authors found no evidence that it is effective at
      preventing contrast nephropathy. The reasons why HD treatment was not beneficial
      in those three studies are not known. Perhaps, the rapid onset of renal injury
      after administration of contrast media is one answer. It is also possible that HD
      per se was nephrotoxic and might have offset the beneficial effect of the removal
      of contrast media. Marenzi et al. randomized 114 consecutive patients with
      chronic renal failure undergoing coronary interventions to either hemofiltration
      in an intensive care unit or isotonic saline hydration. The authors concluded
      that periprocedural hemofiltration given in an intensive care unit setting
      appears to be effective in preventing the deterioration of renal function due to
      contrast agent induced nephropathy and is associated with improved in-hospital
      and long term outcomes. The concentration of contrast media can effectively be
      reduced by HD and peritoneal dialysis. HD does not offer any protection against
      contrast media induced nephrotoxicity. Hemofiltration may decrease the risk of
      contrast induced nephropathy and have some long-term benefits, but additional
      studies are needed to better define the appropriate population for this
      treatment.

PMID- 16612398
TI  - Contrast-induced nephrotoxicity: clinical landscape.
AB  - Over 80 million doses of iodinated intravascular contrast media (CM) were
      administered in the most recent tabulations of 2003, corresponding to
      approximately 8 million liters, making it one of the highest volume medical drugs
      used compared to any other pharmaceutical. The evolution of CM has focused on
      minimizing adverse events by eliminating ionicity, increasing hydrophilicity,
      lowering osmolality and increasing the number of iodine atoms per molecule.
      Contrast media are classified into three general categories based on their
      osmolality relative to blood: high osmolar (5 times or greater than blood), low
      osmolar (2-3 times blood) and iso-osmolar (the same as blood). All imaging
      modalities that employ CM, especially computerized tomography (CT), have shown
      rapid growth. In the last two decades, the use of CT scanning has increased by
      800%. From 1979 to 2002, the number of cardiac catheterization procedures in the
      USA increased by 390% and in Europe from 1992 to 1999 by 112%. There is a general
      consensus that renal insufficiency and diabetes are major risk factors for
      contrast-induced nephropathy (CIN), particularly when co-existing. The US Renal
      Data System documents a 'relentless' increase in kidney failure, projecting a 90%
      increase by 2010. Diabetes affects 194 million people worldwide and the number is
      anticipated to increase by 75% by 2025. The unavoidable conclusion is that
      patient exposure and prevalence of risk factors for CIN will continue to
      increase.

PMID- 16612399
TI  - Contrast-induced nephropathy: pharmacological prophylaxis.
AB  - Contrast media-associated acute renal failure represents the third most common
      cause of in-hospital renal function deterioration after decreased renal perfusion
      and post-operative renal insufficiency. Although generally benign, this
      complication is associated with a mortality rate ranging from 3.8 to 64%,
      depending on the increase of creatinine concentration. Multiple drugs have been
      tested in an attempt to prevent this complication. Central to the pathophysiology
      of contrast-induced nephrotoxicity (CIN) is an alteration in renal hemodynamics.
      In an effort to reverse these hemodynamic changes, vasodilators and diuretics
      have been tested as prophylactic drugs. However, their effectiveness has not been
      confirmed. Recently, considerable interest has resulted from the initial positive
      data on the effectiveness of prophylactic administration of antioxidant
      compounds, such as acetylcysteine and ascorbic acid. In this review, we focus on
      the effectiveness of pharmacologic therapies for preventing CIN.

PMID- 16612400
TI  - Selection of contrast media.
AB  - The pathophysiologic mechanisms of contrast-induced nephropathy (CIN) have been
      reviewed by Persson and Tepel. They focus on the renal response to contrast media
      (CM). In this section, we focus on the CM itself. Aspects of importance with
      regard to CIN include the route of administration, the volume of CM, the manner
      of X-ray attenuation, and the specific chemical structure of the CM.

PMID- 16612401
TI  - Follow-up of patients with contrast-induced nephropathy.
AB  - In this chapter, we review the approach to following the patient after contrast
      is administered. We first discuss the clinical importance of renal injury for if
      there were no clinically significant consequences of this renal injury, we would
      have far less concern for the adequacy of follow-up. We next look at markers of
      renal injury and what tests are used in clinical practice to define contrast
      induced nephropathy (CIN). Finally, we discuss the steps that should be taken in
      those who do develop CIN to limit the impact of the injury and protect them from
      future adverse events.

PMID- 16612402
TI  - How to prevent contrast-induced nephropathy and manage risk patients: practical
      recommendations.

PMID- 16612403
TI  - Contrast medium-induced nephropathy: the pathophysiology.
AB  - A widespread, rather general, definition of contrast-induced nephropathy (CIN) is
      an impairment in renal function occurring within 3 days following the
      intravascular administration of contrast media (CM) and the absence of an
      alternative aetiology. In spite of the vast clinical importance of CIN, its
      understanding and the pathophysiology behind CIN remain incomplete. Many studies
      have been performed; however, they have provided no widely accepted conclusion so
      far. Here the possible mechanisms underlying CIN are outlined, which span from
      altered rheological properties, perturbation of renal haemodynamics, regional
      hypoxia, auto-, and paracrine factors (adenosine, endothelin, reactive oxygen
      species) to direct cytotoxic effects. Although these potential mediators of CIN
      will be discussed separately, several factors may act in concert to perturb
      kidney function after exposure to contrast media. From the current knowledge of
      the mechanisms causing CIN, it is not possible to recommend a certain class of
      contrast media, except to avoid large doses of CM of the first generation. From a
      pathophysiological perspective, volume expansion is effective in avoiding CIN,
      since water permeability of the collecting ducts will decrease and enhance fluid
      excretion. Hence, CM in the distal portions of the tubular system is diluted,
      which implies reduced fluid viscosity and a lower risk of obstruction.

PMID- 16612404
TI  - The developing role of receptors and adaptors.
AB  - The response of a cell to the myriad of signals that it receives is varied, and
      it is dependent on many different factors. The most-studied responses involve
      growth-factor signalling and these signalling cascades have become key targets
      for cancer therapy. Recent reports have indicated that growth-factor receptors
      and associated adaptors can accumulate in the nucleus. Are there novel functions
      for these proteins that might affect our understanding of their role in cancer
      and have implications for drug resistance?

PMID- 16612405
TI  - Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic
      leukaemia.
AB  - The chromosomal translocation t(7;9) in human T-cell acute lymphoblastic
      leukaemia (T-ALL) results in deregulated expression of a truncated, activated
      form of Notch 1 (TAN1) under the control of the T-cell receptor-beta (TCRB)
      locus. Although TAN1 efficiently induces T-ALL in mouse models, t(7;9) is present
      in less than 1% of human T-ALL cases. The recent discovery of novel activating
      mutations in NOTCH1 in more than 50% of human T-ALL samples has made it clear
      that Notch 1 is far more important in human T-ALL pathogenesis than previously
      suspected.

PMID- 16612407
TI  - Nephrologists Sans Frontieres: a kidney foundation-- advancing research and
      helping patients meet their needs.

PMID- 16612408
TI  - Truth and trust in scientific publishing.

PMID- 16612409
TI  - Infection hunter: gallium scintigraphy for hemodialysis access graft infection.

PMID- 16612410
TI  - Time to consider ACE insertion/deletion genotypes and individual renoprotective
      treatment in diabetic nephropathy?
AB  - One reason for the inadequacy of current renoprotective therapy and the
      persistent poor renal prognosis in diabetic nephropathy is the large
      interindividual variation in response to treatment. Genetic as well as non
      genetic factors are known to influence treatment efficacy. This Commentary
      summarizes the impact of the angiotensin-converting enzyme (ACE)
      insertion/deletion polymorphism in the ACE gene on initiation and progression of
      diabetic nephropathy.

PMID- 16612411
TI  - Cellular contributions to glomerular size-selectivity.
AB  - The glomerular capillary wall permits free passage of low-molecular-weight
      solutes, while severely restricting large proteins. Although both cell layers
      (endothelium and epithelium) almost certainly contribute to this size
      selectivity, their relative importance has been difficult to assess. The finding
      by Rippe et al. of an inverse relationship between the sieving coefficient of
      Ficoll and glomerular filtration rate sheds light on this.

PMID- 16612412
TI  - Beta2-microglobulin, a uremic toxin with a double meaning.
AB  - beta(2)M is a strong and independent indicator of hemodialysis patient outcomes
      and an excellent surrogate for middle molecules, and deserves to be routinely
      monitored and incorporated into dialysis adequacy targets. beta(2)M has a double
      meaning, reflecting both dialysis efficacy in terms of solute mass transfer and
      patient bioactivity. The work of Ward et al. in this issue warrants a study to
      test the hypothesis that long daily hemodiafiltration treatment would be the
      optimal renal replacement modality to improve dialysis patient outcomes.

PMID- 16612414
TI  - Response to Taylor and Curhan.

PMID- 16612415
TI  - Population characteristics of a recovering US Virgin Islands red hind spawning
      aggregation following protection.
AB  - Many species of groupers form spawning aggregations, dramatic events where 100s
      to 1000s of individuals gather annually at specific locations for reproduction.
      Spawning aggregations are often targeted by local fishermen, making them
      extremely vulnerable to over fishing. The Red Hind Bank Marine Conservation
      District located in St. Thomas, United States Virgin Islands, was closed
      seasonally in 1990 and closed permanently in 1999 to protect an important red
      hind Epinephelus guttatus spawning site. This study provides some of the first
      information on the population response of a spawning aggregation located within a
      marine protected area. Tag-and-release fishing and fish transects were used to
      evaluate population characteristics and habitat utilization patterns of a red
      hind spawning aggregation between 1999 and 2004. Compared with studies conducted
      before the permanent closure, the average size of red hind increased mostly
      during the seasonal closure period (10 cm over 12 yr), but the maximum total
      length of male red hind increased by nearly 7 cm following permanent closure.
      Average density and biomass of spawning red hind increased by over 60% following
      permanent closure whereas maximum spawning density more than doubled. Information
      from tag returns indicated that red hind departed the protected area following
      spawning and migrated 6 to 33 km to a ca. 500 km(2) area. Protection of the
      spawning aggregation site may have also contributed to an overall increase in the
      size of red hind caught in the commercial fishery, thus increasing the value of
      the grouper fishery for local fishermen.

PMID- 16612416
TI  - Harm reduction: milestones, dilemmas, prospects, challenges.

PMID- 16612418
TI  - Debate on the paper by David Vlahov & David D. Celentano. The double dimension of
      care and management of injecting drug users living with HIV/AIDS.

PMID- 16612417
TI  - Access to highly active antiretroviral therapy for injection drug users:
      adherence, resistance, and death.
AB  - Injection drug users (IDUs) continue to comprise a major risk group for HIV
      infection throughout the world and represent the focal population for HIV
      epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged
      from HIV testing and counseling, education, behavioral and network interventions,
      drug abuse treatment, bleach disinfection of needles, needle exchange and
      expanded syringe access, as well as reducing transition to injection and primary
      substance abuse prevention. With the advent of highly active antiretroviral
      therapy (HAART) in 1996, dramatic clinical improvements have been seen. In
      addition, the treatment's impact on reducing HIV viral load (and therefore
      transmission by all routes) provides a stronger rationale for an expansion of the
      focus on prevention to emphasize early identification and treatment of HIV
      infected individuals. However, treatment of IDUs has many challenges including
      adherence, resistance and relapse to high risk behaviors, all of which impact
      issues of access and ultimately effectiveness of potent antiretroviral treatment.
      A major current challenge in addressing the HIV epidemic revolves around an
      appropriate approach to HIV treatment for IDUs.

PMID- 16612419
TI  - Debate on the paper by David Vlahov & David D. Celentano. The question of
      technology transfer: how does that apply to Brazilian reality?

PMID- 16612420
TI  - Debate on the paper by David Vlahov & David D. Celentano.

PMID- 16612421
TI  - Debate on the paper by David Vlahov & David D. Celentano.

PMID- 16612422
TI  - Debate on the paper by David Vlahov & David D. Celentano. Drug users and the
      HIV/AIDS epidemic: old problems, new perspectives.

PMID- 16612423
TI  - Debate on the paper by David Vlahov & David D. Celentano. HIV infection,
      injection drug users and bioethics.

PMID- 16612424
TI  - Debate on the paper by David Vlahov & David D. Celentano.

PMID- 16612425
TI  - Debate on the paper by David Vlahov & David D. Celentano. Access to AIDS
      treatment: appropriateness and correctness in the pursuit of good practice.

PMID- 16612427
TI  - Getting clean and harm reduction: adversarial or complementary issues for
      injection drug users.
AB  - Many contemporary HIV prevention interventions targeting injection drug users
      (IDUs) have been implemented using Harm Reduction as a theoretical framework.
      Among drug-using individuals, however, the abstinence-based "getting clean"
      models espoused by Narcotics Anonymous and other widely adopted approaches to
      drug treatment are often more readily accepted. This paper describes an
      ethnographic examination of the ideological dichotomy between Harm Reduction and
      abstinence-based "getting clean" treatment model which emerged during the
      piloting phase of an HIV prevention intervention in Baltimore City, Maryland,
      USA. This paper describes how the conflict was identified and what changes were
      made to the intervention to help resolve the participants' dichotomous thinking
      concerning their substance abuse issues.

PMID- 16612428
TI  - The HIV/AIDS epidemic and changes in injecting drug use in Buenos Aires,
      Argentina.
AB  - This article discusses the changes in injecting drug use from 1998 to 2003 in
      Buenos Aires, Argentina. The Rapid Situation Assessment and Response methodology
      was used to obtain the information. Quantitative and qualitative techniques were
      triangulated: 140 current IDUs and 35 sex partners of injection drug users (IDUs)
      were surveyed; 17 in-depth interviews with the surveyed IDUs and 2 focus groups
      were held, as well as ethnographic observations. The way in which risk and care
      practices among injecting drug users changed and the influence of the HIV/ AIDS
      epidemic on this process are described. In recent years, the frequency of
      injection practices and sharing of injecting equipment has decreased, while
      injecting drug use is a more hidden practice in a context of increasing impact of
      the disease in the injecting drug use social networks and changes in the price
      and quality of drugs. Knowledge about these changes helps build harm reduction
      activities oriented to IDUs in their particular social context.

PMID- 16612429
TI  - Reconstructing the AIDS epidemic among injection drug users in Brazil.
AB  - The HIV/AIDS epidemic among injection drug users (IDUs) in Brazil has been unique
      in terms of temporal and geographical contrasts. This analysis explores these
      contrasts through the use of multilevel modeling. Standardized AIDS incidence
      rates among IDUs for Brazilian municipalities (1986-2000) were used as the
      dependent variable, with a set of social indicators as independent variables
      (covariates). In some States of the North/Northeast, the epidemic among IDUs has
      been incipient. The Sao Paulo epidemic extended to reach a network of
      municipalities, most of which located far from the capital. More recently, on a
      smaller scale, a similar extension has been observed in the southernmost States
      of the country. Both "number of physicians per inhabitant" and "standard distance
      to the State capital" were found to be associated with AIDS incidence. AIDS cases
      among IDUs appeared to cluster in wealthier, more developed municipalities. The
      relative weight of such extensive dissemination in key, heavily populated States
      prevails in the Brazilian IDU epidemic, defining a central-western-southeastern
      strip of wealthier middle-sized municipalities and more recently a southern strip
      of municipalities deeply affected by the epidemic in this population.

PMID- 16612430
TI  - Syringe exchange programs in Brazil: preliminary assessment of 45 programs.
AB  - The present study aims to evaluate the current operation of Brazilian syringe
      exchange programs (SEP). After consulting national and regional networks of
      people working in projects/programs aiming to reduce drug-related harm, we
      identified 134 potential participant programs. Unfortunately, only 45 SEPs
      answered a survey, even after repeated attempts. The survey addressed: coverage,
      funding, procurement of basic supplies, managerial capacity, and the local
      political environment. Findings were triangulated with in-depth interviews with
      key informants. The main findings included: satisfactory adherence to the
      initiatives and adequate documentation, but deficiencies in terms of coverage and
      monitoring, and uneven procurement of resources. Program personnel work mostly on
      a provisional basis, despite the efforts of local coordinators. Most programs are
      funded by the National STDs/AIDS Program. A comprehensive agenda aiming to
      improve current operations should include: concerted efforts to improve local and
      regional databanks, incentives/sanctions toward full accountability of
      initiatives carried by the programs, and a genuine culture of monitoring and
      evaluation.

PMID- 16612431
TI  - The contribution of two Brazilian multi-center studies to the assessment of HIV
      and HCV infection and prevention strategies among injecting drug users: the AjUDE
      Brasil I and II Projects.
AB  - This study assessed 1,144 Brazilian injecting drug users (IDUs) recruited on the
      street through outreach syringe exchange programs by two multi-center cross
      sectional studies: 287 IDUs were recruited during the AjUDE-Brasil I Project and
      857 during the AjUDE-Brasil II Project. IDU characteristics related to drug use
      and sexual behavior, and legal and health conditions for the two studies were
      compared, using decision tree and logistic regression for each individual study,
      with HIV infection as the outcome. Fifty-two percent of IDUs were HIV-infected in
      AjUDE I versus 36.5% in AjUDE II. In both studies, HIV infection was
      independently associated with: mean background HIV prevalence for each site (OR =
      2.17; 10.66), HCV seropositive status (OR = 19.79; 15.48), and men who reported
      ever having sex with other men (OR = 2.10; 2.09). Incarceration (OR = 1.41) and 8
      or more years of injecting drug (OR = 2.13) were also associated with HIV in
      AjUDE II. The high HIV infection rates and high prevalence of both parenteral and
      sexual risk behaviors in the context of syringe-exchange programs are of great
      concern and demand thorough surveillance and renewed prevention strategies.

PMID- 16612432
TI  - A capture-recapture technique to estimate the size of the injecting drug user
      population attending syringe exchange programs: AjUDE-Brasil II Project.
AB  - This paper presents the results of a study with a two-occasion capture-recapture
      design. The data are part of the AjUDE-Brasil II Project, carried out in 2000
      2001. Estimation of the size of the IDU population attending a syringe-exchange
      program (SEP) in Sao Jose do Rio Preto, Salvador, and Porto Alegre, Brazil, was
      performed using Chao's model. Capture probabilities were also estimated. For
      Porto Alegre a comparison of the results from the AjUDE-Brasil I and AjUDE-Brasil
      II Projects was performed. Results are also presented for error rates secondary
      to the choice of matching criteria.

PMID- 16612433
TI  - Characteristics of male and female injecting drug users of the AjUDE-Brasil II
      Project.
AB  - The object of this study is to compare female and male injection drug users
      (IDUs) in terms of sociodemographic profile and aspects of their initiation to
      the use of injection drugs. It was a cross-sectional and multicentric study
      realized in 2000-2001 in six Brazilian syringe-exchange programs. 146 women and
      709 men were interviewed, with average ages of 29.5 and 28.3 years, respectively.
      Both began injection drug use at similar ages, 18.6 and 19.3, for women and men,
      respectively, although women report more frequently than men that they were
      initiated by a sexual partner to acquiring drugs and syringes, and to the act of
      injection. Compared to men, women report significantly more regular sexual
      partners (83% versus 72%); fewer casual partners (39% versus 58%), more use of
      injection drugs with their partners, as well as more "exchange" of sex for drugs.
      Among HIV-seropositive individuals, women show less education, had more chance of
      their sexual partners participating in their initiation to injection drugs, and
      report sexual partners that used injection drugs more frequently. Female IDUs
      exhibit aspects of behavior indicating greater vulnerability to HIV infection
      than do males.

PMID- 16612434
TI  - Utilization of HIV/AIDS treatment services: comparing injecting drug users and
      other clients.
AB  - This study compared healthcare utilization by injection drug users (IDUs) and non
      IDUs. Data were abstracted from patients' medical records, admitted on HIV/AIDS
      treatment centers, between 1986 and 2002, forming a non-concurrent cohort study.
      Variables included: sociodemographics, HIV/AIDS exposure group, healthcare
      utilization (consultations, procedures, and prescriptions). Descriptive analyses
      included age-period and cohort effects. Out of 170 patients, with an average age
      of 30 years, 39.4% were IDUs, 71.8% were males and had low levels of education.
      At the first consultation, 86.5% neither received an ARV prescription nor had a
      request for CD4 or viral load. Injection drug users, as compared to non-IDUs,
      were less likely to receive ARV prescriptions and requests for CD4 lymphocyte and
      viral load counts, even though the number of consultations did not differ between
      the two groups. Healthcare utilization increased in calendar-year in the non-IDUs
      group, parallel to the implementation of the Brazilian health policy of universal
      care. However, this favorable trend was not observed among IDUs. Differential
      outcomes for HIV/AIDS among IDUs, towards worse prognosis, suggest difficulties
      in terms of adherence and follow-up of ARV therapy in this population.

PMID- 16612435
TI  - Injecting drug users who are (un)aware of their HIV serostatus: findings from the
      multi-center study AjUDE-Brasil II.
AB  - This study aimed to characterize the profiles of injecting drug users (IDUs) who
      were unaware of their HIV serostatus, given the importance of this information
      for prevention strategies, especially in this vulnerable population, key to the
      HIV/AIDS dynamic. As part of a cross-sectional multi-city survey, IDUs were
      interviewed and HIV-tested by the ELISA technique. IDUs were categorized
      according to knowledge of their own HIV status as either aware or unaware. Means,
      averages, and proportions were compared between the groups using bi- and
      multivariate analyses. Of 857 IDUs interviewed, 34.2% were unaware of their HIV
      serostatus. Those who were unaware were more likely: to have been recruited at
      sites where the HIV prevalence rate was considered medium (> 10 to 50%; odds
      ratio = 8.0) or high (> 50%; 4.0); to be illiterate (OR = 4.54); to have no prior
      HIV test (OR = 2.22); to be male (OR = 1.81); and to have been enrolled more
      recently in syringe-exchange programs (OR = 1.69). HIV prevention programs should
      target both individuals at risk and HIV-positive individuals. Programs to expand
      access to HIV testing are pivotal and should be tailored to specific contexts and
      populations.

PMID- 16612436
TI  - AIDS incidence and mortality in injecting drug users: the AjUDE-Brasil II
      Project.
AB  - This paper presents AIDS incidence and mortality among injecting drug users
      (IDUs) reached by the AjUDE-Brasil II Project. From a cross-sectional survey, 478
      IDUs were interviewed in three Brazilian cities: Porto Alegre, Sao Jose do Rio
      Preto, and Itajai. The cohort was followed up in the Brazilian surveillance
      database for AIDS and mortality during 2000 and 2001. AIDS incidence was 1.1
      cases per 100 person-years, and the mortality rate was 2.8 deaths per 100 person
      years. AIDS cases only occurred in IDUs who reported ever having shared injecting
      equipment. Female gender (RR = 5.30), homelessness (RR = 6.16), and report of
      previous sexual relations with same-sex partners (RR = 6.21) were associated with
      AIDS. Deaths occurred only among males. Homelessness (RR = 3.00), lack of income
      (RR = 2.65), HIV seropositive status (RR = 4.52), and no history of incarceration
      (RR = 3.71) were also associated with death. These findings support evidence that
      gender and socioeconomic conditions are both determinants of morbidity and
      mortality in Brazilian IDUs.

PMID- 16612437
TI  - HCV and HIV infection and co-infection: injecting drug use and sexual behavior,
      AjUDE-Brasil I Project.
AB  - This study aimed to characterize sexual and drug-use behaviors in injecting drug
      users (IDUs) in relation to single hepatitis C virus (HCV) and human
      immunodeficiency virus (HIV) infection and HCV/HIV co-infection. The sample
      consisted of 272 IDUs enrolled in the AjUDE-Brasil I Project, a cross-sectional
      multi-center study conducted in five Brazilian cities in 1998. Data were
      collected with a structured questionnaire using self-reported risk behavior, and
      HCV and HIV serological status used ELISA on filter paper. IDUs were clustered in
      four distinct groups: HCV/HIV seronegative; HCV mono-infected; HIV mono-infected;
      and HCV/HIV co-infected. Active sharing of injecting equipment was associated
      with HCV infection (p = 0.001). Sexual behavior variables, especially male same
      sex sexual relations, were consistently associated with HIV infection. HCV/HIV co
      infection was associated with both sexual and drug use variables. It was possible
      to distinguish different behavioral indicators for HCV and HIV infection and co
      infection in this population.

PMID- 16612438
TI  - Profile of male Brazilian injecting drug users who have sex with men.
AB  - This study aims to characterize the profile of male injecting drug users who have
      sex with other men (MSM IDUs) recruited through a cross-sectional multi-city
      survey (AjUDE-Brasil II Project) in six Brazilian cities, in 2000-2001. MSM IDUs
      were compared to other male IDUs using bivariate and multivariate procedures
      (logistic regression and answer tree analysis with the CHAID algorithm). Among
      the 709 male IDUs, 187 (26.4%) reported ever having had sex with other men, while
      only 37 reported sex with other men in the previous six months. MSM IDUs were
      more likely to be unemployed (OR = 2.3), to have injected tranquilizers (OR =
      3.6), and to be HIV-seropositive (OR = 2.1), compared to other male IDUs. Male
      same-sex relations in this subgroup appear to be associated with strategies to
      finance drug consuming habits, including sex for drugs with occasional female
      partners or obtaining injection paraphernalia from occasional sex partners.
      Further studies should focus on this especially vulnerable subgroup of IDUs, due
      to the bidirectional and complex interrelationships between their drug injecting
      habits and sexual risk behaviors.

PMID- 16612439
TI  - "The first shot": the context of first injection of illicit drugs, ongoing
      injecting practices, and hepatitis C infection in Rio de Janeiro, Brazil.
AB  - The context of first drug injection and its association with ongoing injecting
      practices and HCV (hepatitis C virus) infection were investigated. Injection drug
      users (IDUs) (N = 606) were recruited in "drug scenes" (public places, bars) in
      Rio de Janeiro, Brazil, interviewed, and tested for HCV. Sharing of
      needles/syringes was more prevalent at the first injection (51.3%) than at the
      baseline interview (36.8%). Those who shared syringes/needles at first injection
      were more likely to be currently engaged in direct/indirect sharing practices.
      Among young injectors (< 30 years), those reporting sharing of needles/ syringes
      at the first injection were about four times more likely to have been infected by
      HCV. Hepatitis C virus prevalence among active IDUs (n = 272) was 11%. Prison
      history and longer duration of drug injection were identified as independent
      predictors of HCV infection. To effectively curb HCV transmission among IDUs and
      minimize harms associated with risk behaviors, preventive strategies should
      target individuals initiating drug injection beginning with their very first
      injection and discourage the transition from non-injecting use to the self
      injection of illicit drugs.

PMID- 16612440
TI  - Advocacy and coverage of needle exchange programs: results of a comparative study
      of harm reduction programs in Brazil, Bangladesh, Belarus, Ukraine, Russian
      Federation, and China.
AB  - To prevent or mitigate an AIDS epidemic among injecting drug users (IDUs),
      effective activities need to be implemented on a large enough scale to reach and
      assist sufficient numbers of drug users and thereby change their risk behaviors
      related to drug use and sex. Recent work by UNAIDS on "high coverage sites",
      adopting the above strategies, has shown that one of the key elements in
      achieving high coverage is ongoing and sophisticated advocacy. High coverage harm
      reduction sites were studied through literature search and site visits, including
      key informant interviews, review of service statistics, and data analysis, in
      order to document the steps that led to scaling up, the way coverage was defined
      in these sites, and the lessons learned from their efforts. Syringe-exchange
      programs can achieve high coverage of IDUs. Monitoring to determine regular reach
      (those who are in regular contact with harm reduction services) should be added
      to uniform data collection carried out by harm reduction programs. Advocacy is
      crucial to achieving high coverage.

PMID- 16612442
TI  - [Renal function outcome in acute myocardial infarction as a prognostic factor of
      in-hospital events and at one-year follow-up].
AB  - OBJECTIVE: To analyze the role of renal dysfunction at admission or during
      hospitalization in patients with acute myocardial infarction (AMI). METHODS: Two
      hundred and seventy-four patients with AMI were assessed between January 2000 and
      December 2001. Renal function was monitored by serum creatinine (Cr) measurement
      at admission and peak level during hospitalization. Creatinine clearance (CrCl)
      was estimated by the Cockcroft-Gault formula. In-hospital and one-year morbidity
      and mortality were evaluated. RESULTS: Mean age of the population studied was
      62.2 +/- 13.5, and 73% of the patients were male. Renal function was more reduced
      in male patients and in those with systemic arterial hypertension and prior CABG.
      Multivariate analysis showed higher hospital mortality rates associated with
      increased peak serum Cr levels (OR: 1.18 95% CI: 1.18-2.77 p = 0.006), decreased
      baseline CrCl (OR: 0.96 95% CI: 0.93-0.99 p = 0.025) and peak CrCl (OR: 0.96 95%
      CI: 0.92-0.99 p = 0.023). Percent difference between baseline CrCl and the lowest
      CrCl obtained during hospitalization also indicated higher mortality rates (OR:
      1.04 95% CI: 1.00-1.07 p = 0.033). No change was observed in the one-year
      morbidity and mortality from worsening of renal function. CONCLUSION: Renal
      dysfunction at admission and its deterioration during hospitalization have proved
      to be a major prognostic marker for immediate poor outcome.

PMID- 16612443
TI  - [NT pro-BNP levels in pericardial diseases and how they are used as complementary
      evaluation method of diastolic restriction. Initial experience: 25 cases].
AB  - OBJECTIVE: To determine whether NT pro-BNP levels are high in patients reporting
      pericardial diseases, as well as to investigate how they relate to diastolic
      dysfunction echocardiographic measures. METHODS: Twenty-five patients were split
      into two groups: 1) pericardial effusion (PE): 15 patients; 2) constrictive
      pericarditis (CP): 10 patients. A control group was made up with 30 individuals
      reporting no heart disease. Pericardial effusion was evaluated by bidimensional
      echocardiogram, with restriction evaluated by pulsed Doppler of mitral flow. CP
      diagnosis was confirmed by MRI. NT pro-BNP levels were measured by immunoassay
      and detected by electrochemiluminescence. RESULTS: From the 15 PD patients, 14
      reported relevant PD, and only 1, moderate PD. Log NT pro-BNP was shown to be
      higher in PD (p < 0.05), with log mean of 2.31 pg/ml and CP (p < 0.05), with log
      mean of 2.67 pg/ml, when compared to control group, log mean of 1.32 pg/ml. No
      difference was reported between PD and CP (p = 0.149). The NT pro-BNP log showed
      to be correlated to peak velocity of the E wave (r = 0.845; p = 0.001) and with
      E/A (r = 0.717; p = 0.003). CONCLUSION: NT pro-BNP is shown to have increased in
      pericardial diseases, and is associated to diastolic dysfunction. It may serve as
      an additional method in quantifying restriction.

PMID- 16612444
TI  - [Influence of Diabetes Mellitus on immediate results of coronary stent: National
      Center for Cardiovascular Interventions (CENIC) data analysis].
AB  - OBJECTIVE: This study sought to investigate the influence of Diabetes Mellitus
      (DM) on immediate results after coronary stenting implantation (CSI) according to
      clinical presentation. METHODS: Between January, 1997 and December, 2003, 11,874
      diabetic patients underwent CSI, as recorded by CENIC database: 7,386 (62.3%) had
      chronic coronary disease (CCD); 3,142 (26.4%) acute coronary syndrome with non-ST
      segment elevation (ACSNST); and 1,346 (11.3%), reported acute myocardial
      infarction (AMI), with ST Segment elevation. Those groups were compared with
      48,103 non-diabetics: 30,980 (64.5%) with CCD; 10,938 (22.7%), with non-elevated
      ST segments and unstable angina; and 6,185 (12.8%), with AMI. RESULTS: Diabetic
      patients presented worse clinical and angiographic characteristics. Diabetics
      with CCD showed similar incidence of MACE as compared to non-diabetics (0.98% x
      0.91%, p = 0.5971); however, diabetics with ACSNST and AMI reported higher
      incidence of events: 2.76% x 1.46% (p < 0.0001) and 7.87% x 4.1% (p < 0.0001),
      respectively. Multivariate analysis showed DM to act as independent risk
      predictor for larger adverse events under non-elevated ST segment and unstable
      angina (ACSNST) (OR: 1.92 CI: 1.46-2.52 p < 0.0001) and with AMI (OR: 2.0 CI:
      1.57-2.54 p < or = 0.0001) and no influence for CCD (OR: 1.08 CI: 0.83-1.42 p =
      0.5470. CONCLUSION: Diabetic patients with CCD reported similar outcome as
      compared to the non-diabetics; however, those with ACSNST and AMI presented
      higher incidence of major adverse cardiac events during hospital stay.

PMID- 16612445
TI  - [Electrical cardioversion and myocardial injury: evaluation by new cardiac injury
      markers].
AB  - OBJECTIVE: Evaluate, based on the evolution of new biochemical markers of cardiac
      damage, if electrical cardioversion (ECV) causes myocardial injury. METHODS:
      Seventy-six patients (P) submitted to elective ECV for atrial fibrillation or
      atrial flutter were evaluated. Creatine phosphokinase (CPK), CK-MB activity, CK
      MB mass, myoglobin and cardiac troponin I (cTnI) were measured before, and 6 and
      24 hours after ECV. RESULTS: ECV was successful in 58 P (76.3%). Cumulative
      energy (CE) was up to 350 joules (J) in 36 P, from 500 to 650 J in 20 P and from
      900 to 960 J in 20 P; the mean energy delivered being 493 J (+/- 309). The levels
      of cTnI remained within normal limits in all 76 P. The increase of cumulative
      energy led to an elevation of CPK levels (> p value = 0.007), CK-MB activity (> p
      value = 0.002), CK-MB mass (> p value = 0.03), and myoglobin (> p value = 0.015).
      A positive correlation between the cumulative energy and CPK peaks was observed
      (r = 0.660; p < 0.001), CK-MB activity (r = 0.429; p < 0.0001), CK-MB mass (r =
      0.265; p = 0.02), and myoglobin (r = 0.684; p < 0.0001), as well as between the
      number of shocks and the CPK peaks (r = 0.770; p < 0.001), CK-MB activity (r =
      0.642; p < 0.0001), CK-MB mass (r = 0.430; p < 0.0001), and myoglobin (r = 0.745;
      p < 0.0001). CONCLUSION: ECV does not cause myocardial injury detectable by cTnI
      measurement. Elevations of CPK, CK-MB activity, CK-MB mass and myoglobin result
      from skeletal muscle injury and are positively correlated with the CE delivered
      or with the number of shocks.

PMID- 16612446
TI  - [Blood pressure profile along the arterial tree and genetics of hypertension].

PMID- 16612447
TI  - [Different patterns for the 6-minute walk test as a test to measure exercise
      ability in elderly with and without clinically evident cardiopathy].
AB  - OBJECTIVES: Evaluate the correlation between peak oxygen consumption (VO2peak),
      from cardiopulmonary test with the distance covered in the six-minute walk test
      (6MWT) in healthy elderly and with myocardial infarction (MI). METHODS: Thirty
      individuals were studied, with age range 65-87 years (76.03 +/- 4.75), divided
      into 2 groups: Group I--14 with clinically evident coronary heart disease (CHD)
      and Group II--16 without clinically evident CHD. They were submitted to
      cardiopulmonary test (CPT) and 2 types of 6MWT, standard test 6MWTs. Variables
      measure at rest and exertion were heart rate (HR) and respiratory rate (RR),
      blood pressure (BP), distance covered (DC), and Borgs rate subjective perceived
      exertion (RPE). RESULTS: The study showed significant, strong correlation between
      distances covered for both 6MWT, and (VO2peak) obtained from cardiopulmonary test
      (CPT) for all elderly included in the study. When comparing the 6MWT with
      physiotherapist support (6MWTphy) and without support (6MWTw), statistically
      significant difference was observed, with higher average values of the DC, of the
      RH and RR and Borgs RPE in the 6MWTphy, both of the groups. Additionally, the RH
      reached at final the exertion in 6MWTphy was similar to that obtained in CPT
      (p<0.05) suggesting that the 6MWT stimulates higher cardiovascular performance.
      CONCLUSION: 6MWTw, adopted a worldwide, by being submaximal imposes lower
      cardiovascular overburden as compared to 6MWTphy and is probably safer for
      elderly who are cardiopaths.

PMID- 16612448
TI  - [Effects of cimetidine on chronotropic response to cardiopulmonary exercise
      testing].
AB  - OBJECTIVE: To test the hypothesis that the administration of cimetidine will
      modify the chronotropic response to exercise testing through a random clinical
      trial. METHODS: The study selected 24 eligible healthy subjects, ages between 20
      and 68 years, not athletes, who agreed to undergo cardiopulmonary exercise
      testing after the administration of placebo and 400 mg of cimetidine twice a day
      for one week. The tests were performed on a treadmill using a ramp protocol and
      direct analysis of the expired gases. Peak, resting and anaerobic threshold heart
      rate were recorded. RESULTS: The twenty subjects studied were equally distributed
      across sex with mean (+/- SD) age 43 +/- 11 years. Tests on placebo and on
      cimetidine presented similar duration (578 +/- 90 sec vs 603 +/- 131 sec) and
      similar peak oxygen uptake (35 +/- 8 ml/kg.min vs 35 +/- 8 ml/kg.min). Cimetidine
      administration had no significant effect on resting heart rate (75 +/- 10 bpm vs
      74 +/- 8 bpm), heart rate at peak exercise (176 +/- 12 bpm vs 176 +/- 11 bpm),
      and on the difference between the peak and the resting heart rates--delta HR (101
      +/- 14 bpm vs 101 +/- 13 bpm). CONCLUSION: The administration of cimetidine for 7
      days has no significant effect on the chronotropic response to exercise testing.

PMID- 16612449
TI  - [Gender influence on the immediate and medium-term progression after primary
      percutaneous coronary intervention and analysis of independent risk factors for
      death or events].
AB  - OBJECTIVE: Determine gender-related differences and risk factors for death and
      events, both in-hospital and at six-month evolution, of patients admitted within
      the first twelve hours of ST-segment elevation acute myocardial infarction and
      who underwent primary percutaneous coronary intervention. METHODS: Between July
      1998 and December 2000, 199 consecutive patients were enrolled in the study, with
      elevation myocardial infarction and without cardiogenic shock, outcome, in
      hospital and six-month progression were studied. RESULTS: Clinical
      characteristics were similar in both groups, except that women were older than
      men (67.04 +/- 11.53 x 59.70 +/- 10.88, p < 0.0001). In-hospital mortality was
      higher among women (9.1% x 1.5%, p = 0.0171), as was the incidence of major
      events (12.1% x 3.0%, p = 0.0026). The difference in mortality rates remained the
      same at six months (12.1% x 1.5%, p = 0.0026). The multivariate analysis
      predicted death: female gender and an age over eighty years, and major events
      and/or stable angina multivessel: disease and severe ventricular dysfunction.
      CONCLUSION: Female gender and an age over eighty years were independent
      predictors of mortality, six months of patients who had undergone primary
      percutaneous intervention.

PMID- 16612450
TI  - [Study of the prevalence and multiplicity of cardiovascular risk factors in
      hypertensive individuals from the city of Brusque, SC, Brazil].
AB  - OBJECTIVE: To investigate the prevalence and multiplicity of additional risk
      factors (RF) in a population sample of hypertensive smokers, diagnosed and
      enrolled at the Hiperdia Program of the Ministry of Health, in the city of
      Brusque, SC, Brazil. METHODS: Determination of the anthropometrical parameters
      and laboratory variables recognized as cardiovascular risk factors. RESULTS:
      Elevated prevalence of RF in addition to systemic arterial hypertension (SAH) and
      smoking, configuring the multiplicity that concurs with a marked elevation of the
      risk of cardiovascular events in this population sample. CONCLUSION: In
      hypertensive populations, the prevention, identification and RF control measures
      must be implemented; computerized programs such as the Hiperdia/MS can help in
      patients follow-up, allowing a more stringent multidisciplinary approach,
      especially regarding the analysis of the attainment of treatment goals and the
      subsequent decrease of cardiovascular risk.

PMID- 16612451
TI  - [Correlation between biochemical markers and coronary angiography in patients
      with non-ST elevation acute coronary syndromes].
AB  - OBJECTIVE: Investigate the correlation between biochemical markers (TNI, CRP and
      fibrinogen) and anatomical coronary angiographic findings in patients with non-ST
      elevation acute coronary syndromes (NSTE-ACS). METHODS: One blood sample was
      obtained to test for markers, and coronary angiography was performed within the
      first 72 hours after hospitalization. Univariate analysis was used to search for
      correlations between the 3 markers and the angiographic findings in the group of
      patients with an identified ischemia-related artery (IRA), and multivariate
      analysis was performed to investigate the correlation between these markers and
      the presence of unstable atherosclerotic lesions solely in the group with a
      coronary obstruction > 50%. RESULTS: Prospective study conducted with 84
      patients, 65.5% of whom were men. In the IRA-identified group, blood levels of
      the three markers were higher than in the groups with no IRA-identified or with
      normal coronary arteries. The analysis used to evaluate the IRA-identified group
      showed significant correlations between TIMI flow and TN-I (p = 0.006), unstable
      atherosclerotic lesions and TN-I and fibrinogen (p = 0.02 and p = 0.01,
      respectively), and multivessel disease and CRP (p = 0.0005). The multivariate
      analysis showed that CRP, fibrinogen and TN-I were independent predictors of
      unstable atherosclerotic lesions (p = 0.002; p = 0.003 and p = 0.007,
      respectively). CONCLUSION: In NSTE-ACS patients, TN-I, CRP and fibrinogen blood
      levels within the first 10 hours after hospitalization correlated with coronary
      angiographic findings.

PMID- 16612452
TI  - [Comparative study between intermittent (Muller Reanimator) and continuous
      positive airway pressure in the postoperative period of coronary artery bypass
      grafting].
AB  - OBJECTIVE: To compare the effect of the use of intermittent and continuous
      positive airway pressure in postoperative patients undergoing coronary artery
      bypass grafting. METHODS: This study included forty patients divided into two
      groups: one undergoing continuous positive airway pressure (CPAP Group), and the
      other undergoing intermittent pressure (Muller Resuscitator Group). The patients
      were evaluated in relation to the several study variables at the following time
      points: preoperative, 3rd, 24th, and 48th hours. RESULTS: The patient groups were
      homogeneous in relation to the several demographic and clinical variables. The
      values of pO2, pCO2 and sO2 were within normal limits and no significant
      differences were found between the groups. Regarding respirometry, the groups
      showed significant differences in the tidal volume and respiratory rate at the
      48th postoperative hour. Dyspnea and use of accessory muscle in postoperative
      assessments were found with a significantly higher frequency in patients
      undergoing CPAP. Patients undergoing Muller Resuscitator had a normal chest
      radiograph more frequently than did patients undergoing CPAP. CONCLUSION: Both
      devices were shown to be able to keep pO2, pCO2, and sO2 values within normal
      limits. However, when the objective was pulmonary reexpansion with less imposed
      workload, the Muller Resuscitator was more effective because of its prompter
      action and consequently lower levels of dyspnea, respiratory rate (RR) and use of
      accessory muscle were observed.

PMID- 16612453
TI  - [Monocytosis is an independent risk marker for coronary artery disease].
AB  - OBJECTIVES: Inflammation and activation of immune system cells play an important
      role in the pathogenesis of atherosclerosis. This study analyzes the white blood
      count, including neutrophils, eosinophils, lymphocytes, monocytes and basophils,
      of patients with chronic coronary artery disease (CAD) and acute myocardial
      infarction (AMI). METHODS: The white blood cell count was analyzed in 232
      patients without diabetes between the ages of 15 and 88. One hundred and forty
      two patients were angiographically diagnosed with CAD (57 with stable CAD and 85
      with AMI) and compared to 90 control individuals. The control and CAD groups were
      similar in respect to age, body mass index, family history, smoking habits,
      hypertension, HDL and LDL (all variables with p > 0.25). RESULTS: The univariate
      analysis revealed a higher prevalence of leukocytosis in the CAD group, which in
      turn was higher in the AMI patients than the stable CAD patients. The same trend
      was observed for monocytes. However, the distribution of all other cells in the
      complete blood count (CBC) was similar. Multivariate analysis using the logistic
      regression method with the stepwise (all variables) and backward models (p <
      0.25), showed that monocytosis was an independent variable for CAD and AMI.
      CONCLUSION: The number of monocytes, one of the most important components of the
      inflammatory process in the atherosclerosis plaque was an independent risk marker
      for CAD and AMI.

PMID- 16612455
TI  - Comparison between 100-g glucose tolerance test and two other screening tests for
      gestational diabetes: combined fasting glucose with risk factors and 50-g glucose
      tolerance test.
AB  - CONTEXT AND OBJECTIVE: Lack of consensus about which screening tests to use for
      gestational diabetes mellitus (GDM) and difficulties in performing the gold
      standard diagnostic test, the 100-g glucose tolerance test (100-g GTT), justify
      comparison with alternatives. The aim was to compare this with two other
      screening tests: combined fasting glucose with risk factors (FG + RF) and 50-g
      GTT. DESIGN AND SETTING: Prospective longitudinal cohort study in the Hospital
      School of Universidade Federal de Mato Grosso do Sul. METHODS: The three tests
      were performed independently on 341 pregnant women. Sensitivity (S), specificity
      (Sp), positive (PPV) and negative (NPV) predictive values, positive (PLR) and
      negative (NLR) likelihood ratios, and false-positive (FP) and false-negative (FR)
      rates obtained with FG + RF and 50-g GTT were compared with values from 100-g
      GTT. The average one-hour post-intake glucose levels (1hPG) with 50-g and 100-g
      were compared. Students t test was used in the statistical analysis. RESULTS: FG
      + RF led more pregnant women (53.9%) to diagnostic confirmation than did 50-g GTT
      (14.4%). The tests were equivalent for S (86.4 and 76.9%), PPV (98.7 and 98.9%),
      NLR (0.3 and 0.27) and FR (15.4 and 23.1%). Average 1hPG values were similar: 50
      g GTT = 106.8 mg/dl and 100-g GTT = 107.5 mg/dl. CONCLUSION: Diagnostic
      efficiency with simplicity, practicality and low cost make FG + RF more
      appropriate for screening for GDM. The equivalence of 1hPG allows a new, cheaper
      and less uncomfortable protocol to be proposed for screening and diagnosing GDM.

PMID- 16612456
TI  - Computed tomography guided needle biopsy: experience from 1,300 procedures.
AB  - CONTEXT AND OBJECTIVE: Computed tomography (CT) guided biopsy is widely accepted
      as effective and safe for diagnosis in many settings. Accuracy depends on target
      organ and needle type. Cutting needles present advantages over fine needles. This
      study presents experience from CT guided biopsies performed at an oncology
      center. DESIGN AND SETTING: Retrospective study at Hospital do Cancer A. C.
      Camargo, Sao Paulo. METHODS: 1,300 consecutive CT guided biopsies performed
      between July 1994 and February 2000 were analyzed. Nodules or masses were
      suspected as primary malignancy in 845 cases (65%) or metastatic lesion in 455
      (35%). 628 lesions were thoracic, 281 abdominal, 208 retroperitoneal, 134
      musculoskeletal and 49 head/neck. All biopsies were performed by one radiologist
      or under his supervision: 765 (59%) with 22-gauge fine-needle/aspiration
      technique and 535 (41%) with automated 16 or 18-gauge cutting-needle biopsy.
      RESULTS: Adequate samples were obtained in 70-92% of fine-needle and 93-100% of
      cutting-needle biopsies. The specific diagnosis rates were 54-67% for fine-needle
      and 82-100% for cutting-needle biopsies, according to biopsy site. For any site,
      sample adequacy and specific diagnosis rate were always better for cutting-needle
      biopsy. Among 530 lung biopsies, there were 84 pneumothorax (16%) and two
      hemothorax (0.3%) cases, with thoracic drainage in 24 (4.9%). Among abdominal and
      retroperitoneal biopsies, there were two cases of major bleeding and one of
      peritonitis. CONCLUSION: Both types of needle showed satisfactory results, but
      cutting-needle biopsy should be used when specific diagnosis is desired without
      greater incidence of complications.

PMID- 16612457
TI  - Effects of prone position on the oxygenation of patients with acute respiratory
      distress syndrome.
AB  - CONTEXT AND OBJECTIVE: Acute respiratory distress syndrome (ARDS) is
      characterized by arterial hypoxemia, and prone position (PP) is one possible
      management strategy. The objective here was to evaluate the effects of PP on
      oxygenation. DESIGN AND SETTING: Non-randomized, open, prospective, controlled
      clinical trial, in a surgical intensive care unit at a tertiary university
      hospital. METHODS: Forty-one ARDS patients underwent PP for three-hour periods.
      Arterial partial oxygen pressure (PaO2) was measured immediately before changing
      to PP, after 30, 60, 120 and 180 minutes in PP and 60 minutes after returning to
      dorsal recumbent position (DP). The paired-t and Dunnett tests were used.
      RESULTS: A notable clinical improvement in oxygenation (> 15%) was detected in
      78.0% of patients. This persisted for 60 minutes after returning to DP in 56% and
      lasted for 12 and 48 hours in 53.6% and 46.3%, respectively. Maximum improvement
      was seen after 30 minutes in 12.5% of responding patients and after 180 minutes
      in 40.6%. No statistically significant associations between PP response and age,
      gender, weight, PEEP level, tidal volume, respiratory rate, PaO2/FiO2 or duration
      of mechanical ventilation were detected. One accidental extubation and four cases
      of deterioration through oxygenation were detected. The 48-hour mortality rate
      was 17%. CONCLUSIONS: For a significant number of ARDS patients, PP may rapidly
      enhance arterial oxygenation and its inclusion for management of severe ARDS is
      justified. However, it is not a cost-free maneuver and caution is needed in
      deciding on using PP.

PMID- 16612458
TI  - Childhood carcinoid tumors: description of a case series in a Brazilian cancer
      center.
AB  - CONTEXT AND OBJECTIVE: Carcinoid tumors are very rare both in children and
      adults. About 85% of these tumors develop in the gastrointestinal tract. The
      objective of the present study was to describe our experience with children
      treated of carcinoid tumors, and investigate the frequency morphological findings
      and results. DESIGN AND SETTING: Report on case series, at the Department of
      Pediatrics of Centro de Tratamento e Pesquisa Hospital do Cancer, Sao Paulo.
      METHODS: This was a retrospective analysis of clinical pathological data and
      outcomes among children (< 18 years old) with carcinoid tumors admitted from
      January 1, 1990, to December 31, 2001. RESULTS: Nine patients (mean age 12.2
      years) were included: six girls and three boys (2:1), all of them Caucasian. In
      eight cases (89%), the primary tumor site was the appendix and in one (11%) it
      was the left bronchus. For those with primary tumor in the appendix, the main
      complaint was abdominal pain, which led to appendectomy. Only one patient
      underwent right hemicolectomy due to tumor extension into the serosa. The patient
      with bronchial tumor underwent left pneumonectomy. All patients had localized
      disease and are alive and free of disease. They have had follow-ups lasting from
      1 to 11 years (mean of 3.5 years). CONCLUSION: Although the majority of carcinoid
      tumors arise from the appendix, these tumors can also occur in other primary
      sites. Surgical resection at an early stage allows for good prognosis without the
      need for any adjuvant treatment.

PMID- 16612459
TI  - Management of salivary gland adenoid cystic carcinoma: institutional experience
      of a case series.
AB  - CONTEXT AND OBJECTIVE: Salivary gland tumor management requires long-term follow
      up because of tumor indolence and possible late recurrence and distant
      metastasis. Adenoid cystic carcinoma (ACC) accounts for 10-15% of such tumors.
      The aim here was to evaluate surgical and clinical management, staging and follow
      up of ACC patients in one academic institution. DESIGN AND SETTING: Retrospective
      study at Head and Neck Service, Universidade Estadual de Campinas. METHODS: Data
      on 21 patients treated between 1993 and 2003 were reviewed. Management utilized
      clinical staging, histology and imaging. Major salivary gland tumor extent was
      routinely assessed by preoperative ultrasonography. Diagnosis, surgery type,
      margin type (negative/positive), postoperative radiotherapy and recurrence
      (presence/absence) were evaluated. RESULTS: There were eleven major salivary
      gland tumors (52.3%), seven submandibular and four parotid. Ten patients (47.7%)
      had minor salivary gland ACC (all in palate), while the submandibular was the
      most frequently affected major one. Diagnoses were mostly via fine-needle
      aspiration (FNA) and incision biopsy. Frozen sections were used for six patients.
      There was good ultrasound/FNA correlation. Sixteen (76%) had postoperative
      radiotherapy. One (4.7%) died from ACC and five now have recurrent disease: three
      (14.2%) locoregional and two (9.5%) distant metastases. CONCLUSION: Adenoid
      cystic carcinoma has locally aggressive behavior. In 21 cases, of ACC, the facial
      nerve was preserved in all except in the few with gross tumor involvement.
      Treatment was defined from physical examination, imaging, staging and histology.

PMID- 16612460
TI  - Noncompaction of the left ventricle: a new cardiomyopathy is presented to the
      clinician.
AB  - Noncompaction of the left ventricular myocardium is a morphogenetic abnormality
      involving loss of compaction of the myocardial fiber meshwork during intrauterine
      life. It is an extremely rare condition, accounting for only 0.05% of the cases
      evaluated in databanks. It has been described in both genders, in many ethnic
      groups and at different ages. Recently published studies of case series have
      shown a high mortality rate among these patients during follow-up of up to 48
      months. Many cases have so far been misdiagnosed due to poor knowledge of the
      findings relating to this syndrome. There needs to be an attempt at early and
      accurate diagnosis, because of the need to investigate the patients family upon
      such diagnosis, and today this can be achieved using echocardiographic criteria.

PMID- 16612461
TI  - Practical ways to deal with the high burden of cardiovascular disease in
      hemodialysis patients.
AB  - Cardiovascular disease is the main cause of death among hemodialysis patients.
      Although uremia by itself may be considered to be a cardiovascular risk factor, a
      significant proportion of dialysis patients die because of cardiovascular disease
      not directly attributable to uremia. Indeed, many of the cardiovascular diseases
      and cardiovascular risk factors in these patients are common to those occurring
      in the general population and are amenable to intervention. Lack of proper
      medical care during the early stages of renal insufficiency and present-day
      dialysis routines, by failing to correct hypertension, hypervolemia and left
      ventricular hypertrophy in many patients, may also add to the cardiovascular
      burden. The author suggests that, in addition to early treatment and referral to
      a specialist, chronic renal failure patients should undergo intensive
      cardiovascular screening and treatment, and correction of cardiovascular risk
      factors based on guidelines established for the general population.

PMID- 16612462
TI  - Clinical suspicion and parathyroid carcinoma management.
AB  - CONTEXT AND OBJECTIVE: Adequate management of parathyroid carcinoma apparently
      relates to the surgeons ability to identify it at the first operation. The
      objective of this paper was to evaluate the role of clinical suspicion in the
      management of parathyroid carcinoma. DESIGN AND SETTING: Retrospective analysis
      of parathyroid carcinoma patients treated in Department of Head and Neck Surgery,
      Faculdade de Medicina da Universidade de Sao Paulo. METHODS: Cross-sectional
      study of 143 patients who underwent surgery from 1995 to 2000, due to
      hyperparathyroidism. These cases were reviewed to ascertain whether preoperative
      and intraoperative suspicion of parathyroid carcinoma were helpful during the
      operation, and which factors demonstrated the suspicion of cancer best. RESULTS:
      Among 66 patients with primary hyperparathyroidism there were four cases of
      parathyroid carcinoma (6.1%), and one case was found in secondary
      hyperparathyroidism (1.3%). Palpable nodules were found in five patients with
      primary hyperparathyroidism, four of them with parathyroid carcinoma.
      Preoperative levels of calcium in primary hyperparathyroidism with cancer
      patients varied from 12.0 mg/dl to 18.2 mg/dl. Two patients had gross macroscopic
      spread of the tumor to adjacent structures. Except for one patient, with
      extensive disease, tumors were resected en bloc. In secondary
      hyperparathyroidism, parathyroid carcinoma was found in a fifth mediastinal
      gland. One atypical adenoma was observed. CONCLUSIONS: High levels of calcium,
      palpable tumors and adherence to close structures are more common in parathyroid
      carcinoma. These clinical signs may be helpful for decision-making during
      parathyroid surgery.

PMID- 16612463
TI  - High prevalence of morphological subtype FAB M1 in adults with de novo acute
      myeloid leukemia in Sao Jose dos Campos, Sao Paulo.
AB  - CONTEXT AND OBJECTIVE: Geographical variations have been described in acute
      myelogenous leukemia (AML). In Brazil, few studies have been published on this.
      The aim of this study was to demonstrate the high prevalence of French-American
      British (FAB) M1 subtype in adults with de novo AML in Sao Jose dos Campos, State
      of Sao Paulo, Brazil. DESIGN AND SETTING: Retrospective analysis, at Hospital Pio
      XII in Sao Jose dos Campos, a public non-teaching institution. METHODS: Records
      from 39 consecutive adult patients with de novo AML referred to Hospital Pio XII
      between January 2002 and September 2004 were reviewed. Peripheral blood and blood
      marrow smears were reviewed blindly by five hematologists and classified
      according to FAB criteria. The rates of remission, relapse, mortality according
      treatment phase, survival and leukemia-free survival were calculated. RESULTS:
      The prevalence of each category as determined via a consensus among five
      observers was M0: 0%; M1: 43.6%; M2: 30.7%; M3: 12.8%; M4: 5.1%; M5: 2.6%: M6:
      2.6%; and M7: 2.6%. The remission and the relapse rates were 82% and 41%
      respectively. The mortality rate was 69% (induction of remission: 7/39, 17.9%;
      post induction: 10/32, 31.2%; and relapse: 10/16, 62.5%). The survival rate was
      30% and leukemia-free survival was 33%. CONCLUSIONS: The study demonstrated a
      high prevalence of FAB M1 subtype in adults with de novo AML in Sao Jose dos
      Campos. Our data suggest the occurrence of different regional prevalences of FAB
      AML categories in Brazil.

PMID- 16612464
TI  - Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug.
AB  - A high dose of delta9-tetrahydrocannabinol, the main Cannabis sativa (cannabis)
      component, induces anxiety and psychotic-like symptoms in healthy volunteers.
      These effects of delta9-tetrahydrocannabinol are significantly reduced by
      cannabidiol (CBD), a cannabis constituent which is devoid of the typical effects
      of the plant. This observation led us to suspect that CBD could have anxiolytic
      and/or antipsychotic actions. Studies in animal models and in healthy volunteers
      clearly suggest an anxiolytic-like effect of CBD. The antipsychotic-like
      properties of CBD have been investigated in animal models using behavioral and
      neurochemical techniques which suggested that CBD has a pharmacological profile
      similar to that of atypical antipsychotic drugs. The results of two studies on
      healthy volunteers using perception of binocular depth inversion and ketamine
      induced psychotic symptoms supported the proposal of the antipsychotic-like
      properties of CBD. In addition, open case reports of schizophrenic patients
      treated with CBD and a preliminary report of a controlled clinical trial
      comparing CBD with an atypical antipsychotic drug have confirmed that this
      cannabinoid can be a safe and well-tolerated alternative treatment for
      schizophrenia. Future studies of CBD in other psychotic conditions such as
      bipolar disorder and comparative studies of its antipsychotic effects with those
      produced by clozapine in schizophrenic patients are clearly indicated.

PMID- 16612465
TI  - Chemotherapy versus support cancer treatment in advanced gastric cancer: a meta
      analysis.
AB  - The aim of the present study was to compare the efficacy of chemotherapy and
      support treatment in patients with advanced non-resectable gastric cancer in a
      systematic review and meta-analysis of randomized clinical trials that included a
      comparison of chemotherapy and support care treatment in patients diagnosed with
      gastric adenocarcinoma, regardless of their age, gender or place of treatment.
      The search strategy was based on the criteria of the Cochrane Base, using the
      following key words: 1) randomized clinical trials and antineoplastic combined
      therapy or gastrointestinal neoplasm, 2) stomach neoplasm and drug therapy, 3)
      clinical trial and multi-modality therapy, 4) stomach neoplasm and drug therapy
      or quality of life, 5) double-blind method or clinical trial. The search was
      carried out using the Cochrane, Medline and Lilacs databases. Five studies
      fulfilled the inclusion criteria, for a total of 390 participants, 208 (53%)
      receiving chemotherapy, 182 (47%) receiving support care treatment and 6 losses
      (1.6%). The 1-year survival rate was 8% for support care and 20% for chemotherapy
      (RR = 2.14, 95% CI = 1.00-4.57, P = 0.05); 30% of the patients in the
      chemotherapy group and 12% in the support care group attained a 6-month symptom
      free period (RR = 2.33, 95% CI = 1.41-3.87, P < 0.01). Quality of life evaluated
      after 4 months was significantly better for the chemotherapy patients (34%; RR =
      2.07, 95% CI = 1.31-3.28, P < 0.01) with tumor mass reduction (RR = 3.32, 95% CI
      = 0.77-14.24, P = 0.1). Chemotherapy increased the 1-year survival rate of the
      patients and provided a longer symptom-free period of 6 months and an improvement
      in quality of life.

PMID- 16612466
TI  - Chemokines in the cerebrospinal fluid of patients with active and stable
      relapsing-remitting multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      human central nervous system. Although its etiology is unknown, the accumulation
      and activation of mononuclear cells in the central nervous system are crucial to
      its pathogenesis. Chemokines have been proposed to play a major role in the
      recruitment and activation of leukocytes in inflammatory sites. They are divided
      into subfamilies on the basis of the location of conserved cysteine residues. We
      determined the levels of some CC and CXC chemokines in the cerebrospinal fluid
      (CSF) of 23 relapsing-remitting MS patients under interferon-ss-1a therapy and 16
      control subjects using ELISA. MS patients were categorized as having active or
      stable disease. CXCL10 was significantly increased in the CSF of active MS
      patients (mean +/- SEM, 369.5 +/- 69.3 pg/mL) when compared with controls (178.5
      +/- 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active
      MS (144.7 +/- 14.4 pg/mL) than in controls (237.1 +/- 16.4 pg/mL, P < 0.01).
      There was no difference in the concentration of CCL2 and CXCL10 between patients
      with stable MS and controls. CCL5 was not detectable in the CSF of most patients
      or controls. The qualitative and quantitative differences of chemokines in CSF
      during relapses of MS suggest that they may be useful as a marker of disease
      activity and of the mechanisms involved in the pathogenesis of the disease.

PMID- 16612467
TI  - Estrogen receptor 1 gene polymorphisms and coronary artery disease in the
      Brazilian population.
AB  - We examined the association of three established single nucleotide polymorphisms,
      IVS1-397T>C, IVS1-351A>G, and +261G>C, in the ESR1 gene with the prevalence and
      severity of coronary atherosclerosis in a southern Brazilian population of
      European ancestry. Three hundred and forty-one subjects (127 women and 214 men)
      with coronary artery disease (CAD) were classified as having significant disease
      (CAD+ patient group) when they showed 60% or more luminal stenosis in at least
      one coronary artery or major branch segment at angiography; patients with 10% or
      less luminal stenosis were considered to have minimal CAD (CAD- patient group).
      The control sample consisted of 142 subjects (79 women and 63 men) without
      significant disease, in whom coronary angiography to rule out the presence of
      asymptomatic CAD was not performed. The polymorphisms were investigated by
      polymerase chain reaction followed by restriction analyses. In the male sample,
      the +261G>C*C allele was more frequent in CAD+ than CAD- subjects (8 versus 1%, P
      = 0.024). Homozygosity for the C allele of the IVS1-397T>C polymorphism was also
      significantly associated with increased CAD severity (OR: 2.99; 95% CI = 1.35
      6.63; P = 0.007). In agreement with previous findings, these results suggest that
      the IVS1-397T>C*C allele was associated with CAD severity independent of gender,
      whereas the association of the +261G>C variant with CAD was observed in males
      only. The relation between ESR1 variation and CAD may influence clinical
      decisions such as the use of hormone therapy, and additionally will be helpful to
      identify the genetic susceptibility determinants of cardiovascular disease
      development.

PMID- 16612468
TI  - Hyperhomocystinemia in patients with coronary artery disease.
AB  - Hyperhomocystinemia has been related to an increased risk of cardiovascular
      disease in several studies. The C677T polymorphism for the gene that encodes the
      methylenetetrahydrofolate reductase enzyme (MTHFR) and low plasma folate levels
      are common causes of hyperhomocystinemia. Due to differences in nutritional
      patterns and genetic background among different countries, we evaluated the role
      of hyperhomocystinemia as a coronary artery disease (CAD) risk factor in a
      Brazilian population. The relation between homocysteine (Hcy) and the extent of
      CAD, measured by an angiographic score, was determined. A total of 236 patients
      referred for coronary angiography for clinical reasons were included. CAD was
      found in 148 (62.7%) patients and 88 subjects had normal or near normal arteries.
      Patients with CAD had higher Hcy levels [mean (SD)] than those without disease
      (14 (6.8) vs 12.5 (4.0) microM; P = 0.04). Hyperhomocystinemia (Hcy >17.8 microM)
      prevalence was higher in the CAD group: 31.1 vs 12.2% (P = 0.01). After
      adjustment for major risk factors, we found an independent association between
      hyperhomocystinemia and CAD (OR = 2.48; 95% CI = 1.02-6.14). Patients with a more
      advanced coronary score had a higher frequency of hyperhomocystinemia and tended
      to have higher mean Hcy levels. An inverse relation between plasma folate and Hcy
      levels was found (r = -0.14; P = 0.04). Individuals with the MTHFR C677T
      polymorphism had a higher prevalence of hyperhomocystinemia than those without
      the mutated allele. We conclude that hyperhomocystinemia is independently
      associated with CAD, with a positive association between Hcy level and disease
      severity.

PMID- 16612469
TI  - L-carnitine as an ergogenic aid for patients with chronic obstructive pulmonary
      disease submitted to whole-body and respiratory muscle training programs.
AB  - The effects of adding L-carnitine to a whole-body and respiratory training
      program were determined in moderate-to-severe chronic obstructive pulmonary
      disease (COPD) patients. Sixteen COPD patients (66 +/- 7 years) were randomly
      assigned to L-carnitine (CG) or placebo group (PG) that received either L
      carnitine or saline solution (2 g/day, orally) for 6 weeks (forced expiratory
      volume on first second was 38 +/- 16 and 36 +/- 12%, respectively). Both groups
      participated in three weekly 30-min treadmill and threshold inspiratory muscle
      training sessions, with 3 sets of 10 loaded inspirations (40%) at maximal
      inspiratory pressure. Nutritional status, exercise tolerance on a treadmill and
      six-minute walking test, blood lactate, heart rate, blood pressure, and
      respiratory muscle strength were determined as baseline and on day 42. Maximal
      capacity in the incremental exercise test was significantly improved in both
      groups (P < 0.05). Blood lactate, blood pressure, oxygen saturation, and heart
      rate at identical exercise levels were lower in CG after training (P < 0.05).
      Inspiratory muscle strength and walking test tolerance were significantly
      improved in both groups, but the gains of CG were significantly higher than those
      of PG (40 +/- 14 vs 14 +/- 5 cmH2O, and 87 +/- 30 vs 34 +/- 29 m, respectively; P
      < 0.05). Blood lactate concentration was significantly lower in CG than in PG
      (1.6 +/- 0.7 vs 2.3 +/- 0.7 mM, P < 0.05). The present data suggest that
      carnitine can improve exercise tolerance and inspiratory muscle strength in COPD
      patients, as well as reduce lactate production.

PMID- 16612470
TI  - Exercise stress testing before and after successful multivessel percutaneous
      transluminal coronary angioplasty.
AB  - Controversy exists regarding the diagnostic accuracy, optimal technique, and
      timing of exercise testing after percutaneous coronary intervention. The
      objectives of the present study were to analyze variables and the power of
      exercise testing to predict restenosis or a new lesion, 6 months after the
      procedure. Eight-four coronary multi-artery diseased patients with preserved
      ventricular function were studied (66 males, mean age of all patients: 59 +/- 10
      years). All underwent coronary angiography and exercise testing with the Bruce
      protocol, before and 6 months after percutaneous coronary intervention. The
      following parameters were measured: heart rate, blood pressure, rate-pressure
      product (heart rate x systolic blood pressure), presence of angina, maximal ST
      segment depression, and exercise duration. On average, 2.33 lesions/patient were
      treated and restenosis or progression of disease occurred in 46 (55%) patients.
      Significant increases in systolic blood pressure (P = 0.022), rate-pressure
      product (P = 0.045) and exercise duration (P = 0.003) were detected after the
      procedure. Twenty-seven (32%) patients presented angina during the exercise test
      before the procedure and 16 (19%) after the procedure. The exercise test for the
      detection of restenosis or new lesion presented 61% sensitivity, 63% specificity,
      62% accuracy, and 67 and 57% positive and negative predictive values,
      respectively. In patients without restenosis, the exercise duration after
      percutaneous coronary intervention was significantly longer (460 +/- 154 vs 381
      +/- 145 s, P = 0.008). Only the exercise duration permitted us to identify
      patients with and without restenosis or a new lesion.

PMID- 16612471
TI  - Minor segmental wall motion abnormalities detected in patients with Chagas'
      disease have adverse prognostic implications.
AB  - Recent data from our laboratory have shown that patients with the indeterminate
      form of Chagas' disease can have impairment of left ventricular contractility, as
      evaluated by the slope of the left ventricle end-systolic pressure-dimension
      relationship. We also showed that Chagas' disease patients with minimal baseline
      wall motion abnormalities detected by two-dimensional echocardiography have more
      intense contractility impairment when compared to patients with the indeterminate
      form of the disease without this abnormality. The prognostic implications of
      these findings have not been established. We evaluated 59 patients (37-76 years,
      mean = 55 years) with different clinical forms of Chagas' disease, who had normal
      left ventricular global systolic function at baseline (57.6 +/- 6.9%) and who had
      at least one additional echo during clinical follow-up (0.4-17.6; mean 4.6
      years). Group 1 consisted of 14 patients with minor baseline left ventricle wall
      motion abnormalities and group 2 consisted of 45 patients without these
      abnormalities. During follow-up, global left ventricle systolic function
      deterioration was observed in 10 group 1 patients (71.4%) and in only 10 group 2
      patients (22.2%; P < 0.005). Age and duration of follow-up were not independent
      determinants of left ventricular function deterioration in these patients. The
      present data indicate that mild segmental left ventricular wall motion
      abnormalities are associated with worsening of systolic function in Chagas'
      disease patients who have normal baseline global systolic performance.

PMID- 16612472
TI  - Effects of metformin on the glycemic control, lipid profile, and arterial blood
      pressure of type 2 diabetic patients with metabolic syndrome already on insulin.
AB  - Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were
      assessed by a paired analysis before and 6 months after addition of metformin as
      combination therapy to evaluate the impact of the association on glycemic
      control, blood pressure, and lipid profile. This was a historical cohort study in
      which the files of type 2 diabetic patients with metabolic syndrome on insulin
      were reviewed. The body mass index (BMI), waist circumference, lipid profile, A1C
      level, fasting blood glucose level, daily dose of NPH insulin, systolic blood
      pressure, and diastolic blood pressure were assessed in each patient before the
      start of metformin and 6 months after the initiation of combination therapy.
      Glycemic control significantly improved (P < 0.001) after the addition of
      metformin (1404.4 +/- 565.5 mg/day), with 14% of the 57 patients reaching A1C
      levels up to 7%, and 53% reaching values up to 8%. There was a statistically
      significant reduction (P < 0.05) of total cholesterol (229.0 +/- 29.5 to 214.2 +/
      25.0 mg/dL), BMI (30.7 +/- 5.4 to 29.0 +/- 4.0 kg/m2), waist circumference
      (124.6 +/- 11.7 to 117.3 +/- 9.3 cm), and daily necessity of insulin. The
      reduction of total cholesterol occurred independently of the reductions of A1C
      (9.65 +/- 1.03 to 8.18 +/- 1.01%) and BMI and the reduction of BMI and WC did not
      interfere with the improvement of A1C. In conclusion, our study showed the
      efficacy of the administration of metformin and insulin simultaneously without
      negative effects. No changes were detected in HDL-cholesterol or blood pressure.

PMID- 16612473
TI  - High incidence of adverse reactions to initial antiretroviral therapy in Brazil.
AB  - A concurrent prospective study was conducted from 2001 to 2003 to assess factors
      associated with adverse reactions among individuals initiating antiretroviral
      therapy at two public referral HIV/AIDS centers in Belo Horizonte, MG, Brazil.
      Adverse reactions were obtained from medical charts reviewed up to 12 months
      after the first antiretroviral prescription. Cox proportional hazard model was
      used to perform univariate and multivariate analyses. Relative hazards (RH) were
      estimated with 95% confidence intervals (CI). Among 397 charts reviewed, 377
      (95.0%) had precise information on adverse reactions and initial antiretroviral
      treatment. Most patients received triple combination regimens including
      nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase
      inhibitors and protease inhibitors. At least one adverse reaction was recorded on
      34.5% (N = 130) of the medical charts (0.17 adverse reactions/100 person-day),
      while nausea (14.5%) and vomiting (13.1%) were the most common ones. Variables
      independently associated with adverse reactions were: regimens with nevirapine
      (RH = 1.78; 95% CI = 1.07-2.96), indinavir or indinavir/ritonavir combinations
      (RH = 2.05; 95% CI = 1.15-3.64), female patients (RH = 1.93; 95% CI = 1.31-2.83),
      5 or more outpatient visits (RH = 1.94; 95% CI = 1.25-3.01), non-adherence to
      antiretroviral therapy (RH = 2.38; 95% CI = 1.62-3.51), and a CD4+ count of 200
      to 500 cells/mm3 (RH = 2.66; 95% CI = 1.19-5.90). An independent and negative
      association was also found for alcohol use (RH = 0.55; 95% CI = 0.33-0.90).
      Adverse reactions were substantial among participants initiating antiretroviral
      therapy. Specially elaborated protocols in HIV/AIDS referral centers may improve
      the diagnosis, management and prevention of adverse reactions, thus contributing
      to improving adherence to antiretroviral therapy among HIV-infected patients.

PMID- 16612474
TI  - Etiology of diarrheal infections in children of Porto Velho (Rondonia, Western
      Amazon region, Brazil).
AB  - In the present study, 470 children less than 72 months of age and presenting
      acute diarrhea were examined to identify associated enteropathogenic agents.
      Viruses were the pathogens most frequently found in stools of infants with
      diarrhea, including 111 cases of rotavirus (23.6% of the total diarrhea cases)
      and 30 cases of adenovirus (6.3%). The second group was diarrheogenic Escherichia
      coli (86 cases, 18.2%), followed by Salmonella sp (44 cases, 9.3%) and Shigella
      sp (24 cases, 5.1%). Using the PCR technique to differentiate the pathogenic
      categories of E. coli, it was possible to identify 29 cases (6.1%) of
      enteropathogenic E. coli (EPEC). Of these, 10 (2.1%) were typical EPEC and 19
      (4.0%) atypical EPEC. In addition, there were 26 cases (5.5%) of
      enteroaggregative E. coli, 21 cases (4.4%) of enterotoxigenic E. coli, 7 cases
      (1.4%) of enteroinvasive E. coli (EIEC), and 3 cases (0.6%) of enterohemorrhagic
      E. coli. When comparing the frequencies of diarrheogenic E. coli, EPEC was the
      only category for which significant differences were found between diarrhea and
      control groups. A low frequency of EIEC was found, thus EIEC cannot be considered
      to be a potential etiology agent of diarrhea. Simultaneous infections with two
      pathogens were found in 39 diarrhea cases but not in controls, suggesting
      associations among potential enteropathogens in the etiology of diarrhea. The
      frequent association of diarrheogenic E. coli strains was significantly higher
      than the probability of their random association, suggesting the presence of
      facilitating factor(s).

PMID- 16612475
TI  - Effect of a single tetanus-diphtheria vaccine dose on the immunity of elderly
      people in Sao Paulo, Brazil.
AB  - Epidemiological data regarding tetanus and diphtheria immunity in elderly people
      in Brazil are scarce. During the First National Immunization Campaign for the
      Elderly in Brazil in April 1999, 98 individuals (median age: 84 years) received
      one tetanus-dyphtheria (Td) vaccine dose (Butantan Institute, lot number
      9808079/G). Inclusion criteria were elderly individuals without a history of
      severe immunosuppressive disease, acute infectious disease or use of
      immunomodulators. Blood samples were collected immediately before the vaccine and
      30 days later. Serum was separated and stored at -20 degrees C until analysis.
      Tetanus and diphtheria antibodies were measured by the double-antigen ELISA test.
      Tetanus and diphtheria antibody concentrations lower than 0.01 IU/mL were
      considered to indicate the absence of protection, between 0.01 and 0.09 IU/mL
      were considered to indicate basic immunity, and values of 0.1 IU/mL or higher
      were considered to indicate full protection. Before vaccination, 18% of the
      individuals were susceptible to diphtheria and 94% were susceptible to tetanus.
      After one Td dose, 78% became fully immune to diphtheria, 13% attained basic
      immunity, and 9% were still susceptible to the disease. In contrast, 79% remained
      susceptible to tetanus, 4% had basic immunity and 17% were fully immune. Although
      one Td dose increases immunity to diphtheria in many elderly people who live in
      Brazil, a complete vaccination series appears to be necessary for the prevention
      of tetanus.

PMID- 16612476
TI  - HBV vaccination of HCV-infected patients with occult HBV infection and anti-HBc
      positive blood donors.
AB  - Anti-HBc positivity is a frequent cause of donation rejection at blood banks.
      Hepatitis B virus (HBV) infection may also occur in HBsAg-negative patients, a
      situation denoted occult infection. Similarly, very low levels of HBV-DNA have
      also been found in the sera of patients with chronic hepatitis C virus (HCV)
      infection, even in the absence of serum HBsAg. Initially we searched for HBV-DNA
      in serum of 100 blood donors and 50 HCV-infected patients who were HBsAg
      negative/anti-HBc positive by nested-PCR and by an HBV monitor commercial test
      for HBV-DNA. Anti-HBs seroconversion rates were measured in 100 blood donors and
      in 22 patients with chronic HCV infection after HBV vaccination to determine if
      the HBV vaccination could eliminate an occult HBV infection in these individuals.
      Occult HBV infection was detected in proportionally fewer blood donors (6/100 =
      6%) than chronic hepatitis C patients (12/50 = 24%) (P < 0.05). We noted
      seroconversion in 6/6 (100%) HBV-DNA(+) and in 84/94 (89.4%) HBV-DNA(-) blood
      donors (P > 0.05). All subjects who were HBV-DNA(+) before the first dose of HBV
      vaccine (D1), became HBV-DNA(-) after D1, D2, and D3. Among 22 HCV-positive
      patients, 10 HBV-DNA(+) and 12 HBV-DNA(-), seroconversion was observed in 9/10
      (90%) HBV-DNA(+) and in 9/12 (75%) HBV-DNA(-) subjects (P > 0.05). The
      disappearance of HBV-DNA in the majority of vaccinated patients suggests that
      residual HBV can be eliminated in patients with occult infection.

PMID- 16612477
TI  - Renal and extrarenal manifestations of autosomal dominant polycystic kidney
      disease.
AB  - The objective of the present study was to determine the frequency of the most
      common clinical features in patients with autosomal dominant polycystic kidney
      disease in a sample of the Brazilian population. The medical records of 92
      patients with autosomal dominant polycystic kidney disease attended during the
      period from 1985 to 2003 were reviewed. The following data were recorded: age at
      diagnosis, gender, associated clinical manifestations, occurrence of stroke, age
      at loss of renal function (beginning of dialysis), and presence of a family
      history. The involvement of abdominal viscera was investigated by
      ultrasonography. Intracranial alterations were prospectively investigated by
      magnetic resonance angiography in 42 asymptomatic patients, and complemented with
      digital subtraction arteriography when indicated. Mean age at diagnosis was 35.1
      +/- 14.9 years, and mean serum creatinine at referral was 2.4 +/- 2.8 mg/dL. The
      most frequent clinical manifestations during the disease were arterial
      hypertension (63.3%), lumbar pain (55.4%), an abdominal mass (47.8%), and urinary
      infection (35.8%). Loss of renal function occurred in 27 patients (mean age: 45.4
      +/- 9.5 years). The liver was the second organ most frequently affected (39.1%).
      Stroke occurred in 7.6% of the patients. Asymptomatic intracranial aneurysm was
      detected in 3 patients and arachnoid cysts in 3 other patients. In conclusion,
      the most common clinical features were lumbar pain, arterial hypertension,
      abdominal mass, and urinary infection, and the most serious complications were
      chronic renal failure and stroke. Both intracranial aneurysms and arachnoid cysts
      occurred in asymptomatic patients at a frequency of 7.14%.

PMID- 16612478
TI  - Risk factors for excess weight loss and hypernatremia in exclusively breast-fed
      infants.
AB  - Data were prospectively obtained from exclusively breast-fed healthy term
      neonates at birth and from healthy mothers with no obstetric complication to
      determine risk factors for excess weight loss and hypernatremia in exclusively
      breast-fed infants. Thirty-four neonates with a weight loss > or = 10% were
      diagnosed between April 2001 and January 2005. Six of 18 infants who were
      eligible for the study had hypernatremia. Breast conditions associated with
      breast-feeding difficulties (P < 0.05), primiparity (P < 0.005), less than four
      stools (P < 0.001), pink diaper (P < 0.001), delay at initiation of first breast
      giving (P < 0.01), birth by cesarean section (P < 0.05), extra heater usage (P <
      0.005), extra heater usage among mothers who had appropriate conditions
      associated with breast-feeding (P < 0.001), mean weight loss in neonates with
      pink diaper (P < 0.05), mean uric acid concentration in neonates with pink diaper
      (P < 0.0001), fever in hypernatremic neonates (P < 0.02), and the correlation of
      weight loss with both serum sodium and uric acid concentrations (P < 0.02) were
      determined. Excessive weight loss occurs in exclusively breast-fed infants and
      can be complicated by hypernatremia and other morbidities. Prompt initiation of
      breast-feeding after delivery and prompt intervention if problems occur with
      breast-feeding, in particular poor breast attachment, breast engorgement, delayed
      breast milk "coming in", and nipple problems will help promote successful breast
      feeding. Careful follow-up of breast-feeding dyads after discharge from hospital,
      especially regarding infant weight, is important to help detect inadequate breast
      feeding. Environmental factors such as heaters may exacerbate infant dehydration.

PMID- 16612479
TI  - Epidemiological studies in the information and genomics era: experience of the
      Clinical Genome of Cancer Project in Sao Paulo, Brazil.
AB  - Genomics is expanding the horizons of epidemiology, providing a new dimension for
      classical epidemiological studies and inspiring the development of large-scale
      multicenter studies with the statistical power necessary for the assessment of
      gene-gene and gene-environment interactions in cancer etiology and prognosis.
      This paper describes the methodology of the Clinical Genome of Cancer Project in
      Sao Paulo, Brazil (CGCP), which includes patients with nine types of tumors and
      controls. Three major epidemiological designs were used to reach specific
      objectives: cross-sectional studies to examine gene expression, case-control
      studies to evaluate etiological factors, and follow-up studies to analyze genetic
      profiles in prognosis. The clinical groups included patients' data in the
      electronic database through the Internet. Two approaches were used for data
      quality control: continuous data evaluation and data entry consistency. A total
      of 1749 cases and 1509 controls were entered into the CGCP database from the
      first trimester of 2002 to the end of 2004. Continuous evaluation showed that,
      for all tumors taken together, only 0.5% of the general form fields still
      included potential inconsistencies by the end of 2004. Regarding data entry
      consistency, the highest percentage of errors (11.8%) was observed for the follow
      up form, followed by 6.7% for the clinical form, 4.0% for the general form, and
      only 1.1% for the pathology form. Good data quality is required for their
      transformation into useful information for clinical application and for
      preventive measures. The use of the Internet for communication among researchers
      and for data entry is perhaps the most innovative feature of the CGCP. The
      monitoring of patients' data guaranteed their quality.

PMID- 16612480
TI  - Somatic cytogenetic and azoospermia factor gene microdeletion studies in
      infertile men.
AB  - The objective of the present study was to determine the frequency of somatic
      chromosomal anomalies and Y chromosomal microdeletions (azoospermia factor genes,
      AZF) in infertile males who seek assisted reproduction. These studies are very
      important because the assisted reproduction techniques (mainly intracytoplasmic
      sperm injection) bypass the natural selection process and some classical
      chromosomal abnormalities, microdeletions of AZF genes or some deleterious genic
      mutations could pass through generations. These genetic abnormalities can cause
      in the offspring of these patients male infertility, ambiguous external
      genitalia, mental retardation, and other birth defects. We studied 165 infertile
      men whose infertility was attributable to testicular problems (60 were
      azoospermic, 100 were oligospermic and 5 were asthenospermic). We studied 100
      metaphases per patient with GTG banding obtained from temporary lymphocyte
      culture for chromosomal abnormality detection and performed a genomic DNA
      analysis using 28 Y chromosome-specific sequence-tagged sites for Y AZF
      microdeletion detection. Karyotyping revealed somatic anomalies in 16 subjects
      (16/165 = 9.6%). Of these 16, 12 were in the azoospermic group (12/60 = 20%) and
      4 were in the oligospermic group (4/100 = 4%). The most common chromosomal
      anomaly was Klinefelter syndrome (10/165 = 6%). Microdeletions of AZF genes were
      detected in 12 subjects (12/160 = 7.5%). The frequencies detected are similar to
      those described previously. These results show the importance of genetic
      evaluation of infertile males prior to assisted reproduction. Such evaluation can
      lead to genetic counseling and, consequently, to primary and secondary prevention
      of mental retardation and birth defects.

PMID- 16612481
TI  - Disseminating child & adolescent mental health treatment methods: an
      international feasibility study.

PMID- 16612482
TI  - [Conflicts of interests and their repercussions on science].

PMID- 16612483
TI  - How do experts recognize schizophrenia: the role of the disorganization symptom.
AB  - OBJECTIVE: Research on clinical reasoning has been useful in developing expert
      systems. These tools are based on Artificial Intelligence techniques which assist
      the physician in the diagnosis of complex diseases. The development of these
      systems is based on a cognitive model extracted through the identification of the
      clinical reasoning patterns applied by experts within the clinical decision
      making context. This study describes the method of knowledge acquisition for the
      identification of the triggering symptoms used in the reasoning of three experts
      for the diagnosis of schizophrenia. METHOD: Three experts on schizophrenia, from
      two University centers in Sao Paulo, were interviewed and asked to identify and
      to represent the triggering symptoms for the diagnosis of schizophrenia according
      to the graph methodology. RESULTS: Graph methodology showed a remarkable
      disagreement on how the three experts established their diagnosis of
      schizophrenia. They differed in their choice of triggering-symptoms for the
      diagnosis of schizophrenia: disorganization, blunted affect and thought
      disturbances. CONCLUSIONS: The results indicate substantial differences between
      the experts as to their diagnostic reasoning patterns, probably under the
      influence of different theoretical tendencies. The disorganization symptom was
      considered to be the more appropriate to represent the heterogeneity of
      schizophrenia and also, to further develop an expert system for the diagnosis of
      schizophrenia.

PMID- 16612484
TI  - Depression in women infected with HIV.
AB  - OBJECTIVE: The number of women with HIV infection has been on the rise in recent
      years, making studies of the psychiatric aspects of this condition very
      important. The aim of this study was to evaluate the prevalence of major
      depression in women with HIV infection. METHOD: A total of 120 women were
      studied, 60 symptomatic (with AIDS symptoms) and 60 asymptomatic (without AIDS
      symptoms). Sociodemographic data were collected, and depressive disorders were
      identified. The instruments used to evaluate the depressive disorders were the
      SCID, DSM-IV, 17-item Hamilton depression scale, Hamilton depression scale for
      nonsomatic symptoms and the Beck depression scale. RESULTS: The prevalence of
      major depression was 25.8% and was higher in the symptomatic group than in the
      asymptomatic group (p = 0.002). CONCLUSIONS: The prevalence of major depressive
      episodes in women with HIV infection is high, and women with AIDS-related
      symptoms are more often depressed than are those who have never presented such
      symptoms.

PMID- 16612485
TI  - Effect of isopregnanolone on rapid tolerance to the anxiolytic effect of ethanol.
AB  - OBJECTIVE: It has been shown that neurosteroids can either block or stimulate the
      development of chronic and rapid tolerance to the incoordination and hypothermia
      caused by ethanol consumption. The aim of the present study was to investigate
      the influence of isopregnanolone on the development of rapid tolerance to the
      anxiolytic effect of ethanol in mice. METHOD: Male Swiss mice were pretreated
      with isopregnanolone (0.05, 0.10 or 0.20 mg/kg) 30 min before administration of
      ethanol (1.5 g/kg). Twenty-four hours later, all animals we tested using the plus
      maze apparatus. The first experiment defined the doses of ethanol that did or did
      not induce rapid tolerance to the anxiolytic effect of ethanol. In the second,
      the influence of pretreatment of mice with isopregnanolone (0.05, 0.10 or 0.20
      mg/kg) on rapid tolerance to ethanol (1.5 g/kg) was studied. CONCLUSIONS: The
      results show that pretreatment with isopregnanolone interfered with the
      development of rapid tolerance to the anxiolytic effect of ethanol.

PMID- 16612486
TI  - Validation study of the Multicultural Quality of Life Index (MQLI) in a Peruvian
      sample.
AB  - OBJECTIVE: The Multicultural Quality of Life Index is a concise instrument for
      comprehensive, culture-informed, and self-rated assessment of health-related
      quality of life. It is composed of 10 items (from physical well-being to global
      perception of quality of life). Each item is rated on a 10-point scale. The
      objective was to evaluate the reliability (test-retest), internal structure,
      discriminant validity, and feasibility of the Multicultural Quality of Life Index
      in Lima, Peru. METHOD: The reliability was studied in general medical patients (n
      = 30) hospitalized in a general medical ward. The Multicultural Quality of Life
      Index was administered in two occasions and the correlation coefficients ("r")
      between both interviews were calculated. Its discriminant validity was studied
      statistically comparing the average score in a group of patients with AIDS (with
      presumed lower quality of life, n = 50) and the average score in a group of
      dentistry students and professionals (with presumed higher quality of life, n =
      50). Data on its applicability and internal structure were compiled from the 130
      subjects. RESULTS: A high reliability correlation coefficient (r = 0.94) was
      found for the total score. The discriminant validity study found a significant
      difference between mean total score in the samples of presumed higher (7.66) and
      lower (5.32) quality of life. The average time to complete the Multicultural
      Quality of Life Index was less than 4 minutes and was reported by the majority of
      subjects as easily applicable. A high Cronbach's a (0.88) was also documented.
      CONCLUSIONS: The results reported that the Multicultural Quality of Life Index is
      reliable, has a high internal consistency, is capable of discriminating groups of
      presumed different quality of life levels, is quite efficient, and easy to use.

PMID- 16612487
TI  - Hypericum perforatum versus fluoxetine in the treatment of mild to moderate
      depression: a randomized double-blind trial in a Brazilian sample.
AB  - OBJECTIVE: Hypericum perforatum has demonstrated antidepressant efficacy when
      compared to placebo, but comparisons with other antidepressants remain
      controversial. We assessed the efficacy and safety of Hypericum perforatum in
      comparison with fluoxetine, in a 8-week double-blind trial in patients with mild
      to moderate depression. METHOD: Seventy-two outpatients were randomly assigned to
      receive Hypericum perforatum 900 mg/day, fluoxetine 20 mg/day or placebo.
      Efficacy measures included the HAM-D21 scale, the Montgomery-Asberg Rating Scale,
      and the Clinical Global Impression. Safety was assessed with the UKU Side Effect
      Rating Scale. RESULTS: Intention-to-treat analysis showed no differences between
      the mean scores of the three groups. In the analyses of observed cases, patients
      receiving Hypericum perforatum had the lowest remission rates (12%, p = 0.016)
      compared to fluoxetine (34.6%) and placebo (45%). CONCLUSIONS: Hypericum
      perforatum was less efficacious than both fluoxetine and placebo. Both drugs were
      safe and well-tolerated. Larger trials are needed for definite conclusions.

PMID- 16612488
TI  - Lead levels and cognitive abilities in Peruvian children.
AB  - OBJECTIVE: To study the relationship between blood lead levels and cognitive
      abilities of children exposed to this metal. METHOD: This is a cross-sectional
      study that included 134 children aged 6 to 8.5 years old from 3 schools with
      different risks of lead exposure located in El Callao (Peru). Cognitive
      assessments were made by means of the Graphic Test of Reasoning (GTR) and the
      Kohs Block Design Test (KBDT). Blood lead levels and other laboratory tests were
      performed. RESULTS: Children with lead > 10 ug/dl presented greater prevalence of
      low scores in the Graphic Test of Reasoning (18.9% vs. 7.1%, p = 0.049) and in
      the Kohs Block Design Test (KBDT) (39.6% vs. 18.6%, p = 0.01) compared with those
      with lower lead blood levels. A deficit of 1 category in the Graphic Test of
      Reasoning was associated with an increase in lead blood level of 16.78 ug/dl
      (assuming a linear relationship) and from 1 to 5.19 ug/dl (logarithmic model).
      For each 10 ug/dl of increase in lead levels, the Kohs Block Design Test
      decreases in 6.24 units (12.91 in males and 0.216 in females) (linear model), and
      an increase from 1 to 10 ug/dl corresponds to a drop of 16.44 points in the Kohs
      Block Design Test (31.19 in males and 3.98 in females) (logarithmic model).
      Considering the Graphic Test of Reasoning subscales, lead levels correlated
      negatively with the areas of numerical problems (rho = -0.445, p < 0.001),
      numerical relationships (rho = -0.365, p < 0.001), inferences (rho = -0.281, p =
      0.002) and similarities (rho = -0.250, p = 0.005). CONCLUSIONS: Lead levels were
      non-linearly associated with lower cognitive abilities, especially in males,
      being the numerical reasoning the most affected area.

PMID- 16612489
TI  - Psychodramatic psychotherapy combined with pharmacotherapy in major depressive
      disorder: an open and naturalistic study.
AB  - OBJECTIVE: Recent literature has highlighted the role of psychotherapy in the
      treatment of major depressive disorder. Combined therapies comprising both
      psychotherapy and pharmacotherapy have presented the best results. Although
      several kinds of psychotherapies have been studied in the treatment of depressive
      disorders, there remains a lack of data on psychodramatic psychotherapy in the
      treatment of major depressive disorder. The objective of this study was to
      evaluate the impact of psychodramatic psychotherapy (in a sample of major
      depressive disorder patients. METHOD: This is an open, naturalistic, controlled,
      non-randomized study. Twenty major depressive disorder patients (according to the
      DSM-IV criteria), under pharmacological treatment for depression, with Hamilton
      Depression Scale total scores between 7 and 20 (mild to moderate depression),
      were divided into two groups. Patients in the psychotherapeutic group took part
      in 4 individual and 24 structured psychodramatic group sessions, whilst subjects
      in the control group did not participate in this psychodramatic psychotherapy.
      Both groups were evaluated with the Social Adjustment Scale-Self Report and the
      Hamilton Depression Scale. RESULTS: Psychotherapeutic group patients showed a
      significant improvement according to the Social Adjustment Scale-Self Report and
      the Hamilton Depression Scale scores at endpoint, compared to those of the
      control group. CONCLUSIONS: Results suggest that individual and group
      psychodramatic psychotherapy, associated to pharmacological treatment, provides
      good clinical benefits in the treatment of major depressive disorder.

PMID- 16612490
TI  - [Transcranial magnetic stimulation in neuropsychology: new horizons for brain
      research].
AB  - This review addresses the use of transcranial magnetic stimulation as a research
      tool of neuropsychological functions. Transcranial magnetic stimulation is a non
      invasive and painless technique to modulate brain function that can be applied to
      conscious human beings and is based on a variable magnetic field. Using this
      technique, it is possible to generate virtual transient lesions in healthy people
      or modulate the brain activity, increasing or decreasing the activity of the
      stimulated areas. In this review we discuss studies with transcranial magnetic
      stimulation in which broad aspects of language, memory and neuropsychological
      tests have been evaluated following or during the application of transcranial
      magnetic stimulation. We concluded that transcranial magnetic stimulation open
      new horizons for brain research in the neuropsychological field as transcranial
      magnetic stimulation allows the investigation of the relationship between focal
      cortical activity and behavior therefore contributing to the study of the
      functional brain activity.

PMID- 16612491
TI  - [Associated factors to quality of life of patients with schizophrenia].
AB  - OBJECTIVE: Treatment of individuals with schizophrenia in Brazil has been
      gradually shifting from an almost exclusively hospital-based approach to a
      community-based treatment. These patients have received treatments focused less
      on symptoms reduction, and more on social reintegration and improvement of their
      life conditions. Thus, it is necessary to evaluate the quality of life of these
      patients living in the community. METHOD: A review of studies was carried out to
      describe the distribution of sociodemographic and clinical factors that may
      influence quality of life of individuals with schizophrenia. RESULTS: Twenty-five
      studies were selected, most of them from European countries. The majority of
      these studies was developed in the 90's. Almost all studies were cross-sectional,
      and most of them evaluated samples of individuals living in the community.
      Sociodemographic factors, other than monthly income, were not associated to
      quality of life. However, some studies found associations between quality of life
      and gender, age, marital status and educational level. Depressive and anxiety
      symptoms were related to worse quality of life in several studies. Such finding
      was also true for negative and positive symptoms of schizophrenia, but without an
      homogeneous pattern. CONCLUSIONS: Generally, studies were not consistent
      regarding association between sociodemographic and clinical factors and quality
      of life of patients with schizophrenia. These lack of homogeneity may be due to
      either disease-related issues or design aspects of these studies, not adequate
      for causal inference.

PMID- 16612492
TI  - Implementation of evidence-based practices for children in four countries: a
      project of the World Psychiatric Association.
AB  - OBJECTIVE: The present study examined implementation issues in adopting cognitive
      behavioral therapies in routine clinical settings in four countries reflecting
      diverse cultures, languages, settings, and traditions. METHOD: A Director's
      Systems Survey was administered prior to program implementation and one year
      later. Therapist ratings on attitudes about evidence-based practices and
      satisfaction were also gathered. RESULTS: All sites reported successful adoption
      of the program, although significant variations existed in fiscal support, family
      involvement, prior experience with cognitive-behavioral therapies, and plans for
      sustainability. Therapists' ratings indicated overall satisfaction with the
      implementation of the project. Findings from the Director's Systems Survey
      pointed to five factors facilitating implementation: 1) early adoption and
      guidance by innovative leaders (i.e., the Directors); 2) attention to the "fit"
      between the intervention model and local practices; 3) attention to front-end
      implementation processes (e.g., cultural adaptation, translation, training,
      fiscal issues); 4) attention to back-end processes early in the project (e.g.,
      sustainability); and 5) establishing strong relationships with multiple
      stakeholders within the program setting. CONCLUSIONS: The implementation issues
      here mirror those identified in other studies of evidence-based practices uptake.
      Some of the obstacles to implementation of evidence-based practices may be
      generic, whereas issues such as the impact of political/economic instability,
      availability of translated materials, constitute unique stressors that
      differentially affect implementation efforts within specific countries.

PMID- 16612493
TI  - Development of adaptable and flexible treatment manuals for externalizing and
      internalizing disorders in children and adolescents.
AB  - In this paper we describe the process used to develop treatment manuals for
      internalizing and externalizing disorders in children and adolescents. These
      manuals were developed to offer health care providers and others working in child
      mental health a flexible intervention that could be adapted to different
      countries and localities based on: 1) the amount of health care and school
      resources that are available; 2) the nature and severity of the types of problems
      children have; and 3) the preferences and cultural factors that are important
      within these communities. We also discuss the experiences and cultural issues
      faced by sites in Egypt, Lebanon, Israel, and Brazil who volunteered to implement
      the manualized treatment programs. The feedback received from these sites
      indicates that the manuals can be implemented to help children with internalizing
      and externalizing problems.

PMID- 16612494
TI  - Training of evidence-based assessment and intervention approaches in cross
      cultural contexts: challenges and solutions.
AB  - Dissemination of evidence-based assessment and intervention approaches for child
      and adolescent with behavioral and/or emotional problems is now a priority in the
      field worldwide. However, developing staff competence in evidence-based
      assessment and intervention approaches in different countries is complicated by
      some environmental and economic constraints. In this paper a distance
      training/supervision model is discussed. We describe seven specific challenges
      encountered and solutions used for overcoming the obstacles in order to implement
      evidence-based assessment and intervention approaches in different sites in
      Brazil, Egypt, Israel, and Lebanon.

PMID- 16612495
TI  - An examination of cross-cultural systems implementing evidence-based assessment
      and intervention approaches.
AB  - Implementation of evidence-based assessment and intervention approaches for youth
      with behavioral and/or emotional problems is rising to recognition worldwide.
      Feasibility research is critical to examine what characteristics of systems allow
      for success or barriers to the implementation of evidence-based practices into
      real-world settings, especially when working cross-culturally. This paper briefly
      reviews the experience of 4 international sites to understand how the overall
      structure and specific site variables directed the implementation of the World
      Health Organization and the World Psychiatry Association project. Discussion
      includes a thematic summary of the successes and challenges experienced by the
      sites, and future directions of feasibility studies.

PMID- 16612496
TI  - Plus-maze following the microinjection of muscimol into the dorsal periaqueductal
      gray of the rat.

PMID- 16612497
TI  - [Mogens Schou and the use of lithium in psychiatry].

PMID- 16612498
TI  - Bipolar disorder: building the path of return to the ideas of Kraepelin.

PMID- 16612500
TI  - [The article by GREA-USP do not declare conflicts of interest].

PMID- 16612501
TI  - [Agranulocytosis induced by interferon-alpha and ribavirin in a patient with
      schizophrenia using clozapine].

PMID- 16612502
TI  - [Anorexia nervosa and mitochondrial neurogastrointestinal encephalomyopathy in
      male].

PMID- 16612505
TI  - Physiological changes in Biomphalaria glabrata Say, 1818 (Pulmonata: Planorbidae)
      caused by sub-lethal concentrations of the latex of Euphorbia splendens var.
      hislopii N.E.B (Euphorbiaceae).
AB  - Molluscides have been used as one of the strategies to control schistosomiasis.
      Many plant extracts with molluscidal effects have been tested, but the action of
      the latex of Euphorbia splendens var. hislopii is considered the most promising
      because it meets the recommendations of the World Health Organization (WHO). The
      objective of this study was to determine the lethal dose and identify the effects
      of the different doses of latex of E. splendens var. hislopii on the physiology
      of Biomphalaria glabrata submitted to treatment for 24 h. The concentrations of
      glucose, uric acid and total proteins in the hemolymph and of glycogen in the
      digestive gland and cephalopodal mass were determined. The LD50 value was 1 mg/l.
      The highest escape index was found to be at a concentration of 0.6 mg/l. The
      results showed that the latex of E. splendens var. hislopii caused a sharp
      reduction in the reserves of glycogen in the digestive gland and elevation of the
      protein content in the hemolymph of B. glabrata.

PMID- 16612506
TI  - Recombinant tegumental protein Shistosoma japonicum very lowdensity lipoprotein
      binding protein as a vaccine candidate against Schistosoma japonicum.
AB  - A polyhistidine-tagged recombinant tegumental protein Schistosoma japonicum very
      lowdensity lipoprotein binding protein (SVLBP) from adult Schistosoma japonicum
      was expressed in Escherichia coli. The affinity purified rSVLBP was used to
      vaccinate mice. The worm numbers and egg deposition recovered from the livers and
      veins of the immunized mice were 33.5% and 47.6% less than that from control
      mice, respectively (p<0.05). There was also a marked increase in the antibody
      response in vaccinated mice: the titer of IgG1 and IgG2a, IgG2b in the vaccinated
      group was significantly higher than that in the controls (>1:6,400 in total IgG).
      In a comparison of the reactivity of sera from healthy individuals and patients
      with rSVLBP, recognition patterns against this parasite tegumental antigen varied
      among different groups of the individuals. Notably, the average titres of anti
      rSVLBP antibody in sera from faecal egg-negative individuals was significantly
      higher than that in sera from the faecal egg-positives, which may be reflect
      SVLBP-specific protection. These results suggested that the parasite tegumental
      protein SVLBP was a promising candidate for further investigation as a vaccine
      antigen for use against Asian schistosomiasis.

PMID- 16612507
TI  - Taeniosis-cysticercosis complex in individuals of a peasants' settlement (Teodoro
      Sampaio, Pontal of Paranapanema, SP, Brazil).
AB  - In order to evaluate the taeniosis-cysticercosis complex in a population of a
      peasants' settlement, located at Teodoro Sampaio, state of Sao Paulo, Brazil
      (longitude 52 degrees 36'12 ", latitude 22 degrees 17'12 ") a series of
      laboratory markers were determined. After signing an informed consent,
      participants answered a standardized questionnaire. To determine anti-Taenia
      solium cysticercus antibodies, the samples were tested by enzyme linked
      immunoabsorbent assay using 18-and 14-kDa antigen proteins from vesicular fluid
      of Taenia crassiceps (VF-Tcra). The reactive and inconclusive ELISA samples were
      tested by immunoblotting. Total IgE levels were determined by
      chemmiluminescence's assay and hemogram by flow cytometer flux counter. A total
      of 84 individuals, 5.9% presented anti-T. solium cysticercus antibodies in ELISA
      and 3.6% were strongly reactive in the 18/14 kDa immunoblotting confirmatory
      test. All of the individuals with positive antibodies showed elevated Total IgE
      levels. We conclude that the frequency of anti-T. solium cysticercus antibodies
      in this population is higher than other regions considered endemic in Sao Paulo.
      Thus, it is important to carry out surveys in Peasants' settlement areas with the
      objective of establishing public health measures for prevention and control of
      infectious diseases such as taeniosis-cysticercosis.

PMID- 16612508
TI  - Frequency of viruses associated with acute respiratory infections in children
      younger than five years of age at a locality of Mexico City.
AB  - A locality in the district of Tlalpan, Mexico City, was selected in order to
      identify the viral agents in children younger than 5 years of age with acute
      respiratory infection (ARI). A total of 300 children were randomly selected and
      were included in this study for a period of 13 months. During this period
      nasopharyngeal exudates were collected for the isolation of viral agents.
      Monoclonal fluorescent antibodies were used for viral identification after cell
      culture. Viral infection was detected in 65% of the specimens. The respiratory
      syncytial virus (RSV) was the most common virus agent detected. Children required
      an average of two consultations during the study period. Two high incidence peaks
      were observed, one during the summer and the other during winter; the most
      frequent viruses during these seasons were influenza A and RSV, respectively. The
      largest number of viruses was isolated in the group of children between 1 and 2
      years of age and in the group between 4 and 5 years of age. This study
      demonstrated the presence of ARI and of different viruses in a period of 13
      months, as well as the most frequent viruses in children younger than 5 years of
      age from a community of Mexico City.

PMID- 16612509
TI  - Molecular trees of trypanosomes incongruent with fossil records of hosts.
AB  - Molecular trees of trypanosomes have confirmed conventionally accepted genera,
      but often produce topologies that are incongruent with knowledge of the
      evolution, systematics, and biogeography of hosts and vectors. These distorted
      topologies result largely from incorrect assumptions about molecular clocks. A
      host-based phylogenetic tree could serve as a broad outline against which the
      reasonability of molecular phylogenies could be evaluated. The host-based tree of
      trypanosomes presented here supports the " invertebrate first " hypothesis of
      trypanosome evolution, supports the monophyly of Trypanosomatidae, and indicates
      the digenetic lifestyle arose three times. An area cladogram of Leishmania
      supports origination in the Palaearctic during the Palaeocene.

PMID- 16612510
TI  - High exposure to Tunga penetrans (Linnaeus, 1758) correlates with intensity of
      infestation.
AB  - Tungiasis is a parasitic skin disease widespread in resource-poor urban and rural
      communities in Brazil. Inhabitants of an urban slum in Northeast Brazil were
      examined for the presence of tungiasis lesions and followed-up twice a week for a
      period of three weeks. Each time the number, stages, and topographic localization
      of lesions were recorded on a documentation sheet. The infestation rate (number
      of newly embedded sand fleas per individual and day) remained stable during the
      observation period. The infestation rate was significantly related to the
      intensity of infestation (total number of lesions present) (rho = 0.70, p <
      0.0001) and the proportion of viable lesions (rho = 0.28, p < 0.0001). The
      results indicate that in an endemic area the infestation intensity and the
      proportion of viable lesions can be used as a proxy to assess the exposure of
      individuals at risk for tungiasis. Persistently high infestation rates during the
      transmission season favour the use of prevention measures against invading sand
      fleas (such as a repellent) rather than a drug to kill already embedded
      parasites.

PMID- 16612511
TI  - Evaluation of the dot enzyme-linked immunosorbent assay in comparison with
      standard ELISA for the immunodiagnosis of human toxocariasis.
AB  - A dot enzyme-linked immunosorbent assay (dot-ELISA) was standardized using
      excretory-secretory antigens of Toxocara canis for the rapid immunodiagnosis of
      human toxocariasis. Thirty patients with clinical signs of toxocariasis, 20 cases
      with other parasitic diseases, and 40 healthy subjects were tested. A total of
      0.2 ng of antigen per dot, serum dilution of 1:160 and dilution conjugate of
      1:1000 were found optimal. The sensitivity and specificity of the assay were 100
      and 95%, respectively. Comparable sensitivity of dot-ELISA and the standard ELISA
      was obtained, but only 3 cross-reactions occurred in the dot-ELISA, compared with
      6 in the standard ELISA. Dot-ELISA is simple to perform, rapid, and low cost.
      Large-scale screening studies should be done to evaluate its usefulness under
      field conditions.

PMID- 16612513
TI  - Morphometric aspects of the human hypoglossal nerve in adults and the elderly.
AB  - AIM: Perform a morphometric analysis of the myelinic fibers of the right
      hypoglossal nerve, in two age groups; to verify quantitative changes as a result
      of the aging process. STUDY DESIGN: Anatomic. MATERIAL AND METHOD: A 1 cm
      fragment of the right hypoglossal nerve was collected from 12 male corpses
      without any medical history of diseases such as: diabetes, alcoholism, and
      malignant neoplasia. The sample was divided in two groups: group with six corpses
      under sixty years old (adult), and another group with six corpses sixty years old
      or above (elderly). The material was fixed at 2.5% glutaldehyde and 2%
      paraformaldehyde solution; post-fixed at 2% osmium tetroxide; dehydrated with
      increasing ethanol concentrations, and included in epoxy resin. Semi-thin
      sections of 0.3 microm were obtaining, colored in 1% toluidine blue, and
      evaluated with light microscope combined with image analyzing system. The
      following morphometric data were quantified: intraperineural transversal section
      area, number, and diameter of the myelinic fibers. RESULTS: The intraperineural
      area of the hypoglossal nerve was similar in both age groups (p=0.8691). The
      average area in the adult group was 1.697 mm2 and in the elderly group it was
      1.649 mm2. The total number of myelinic fibers of the hypoglossal nerve was
      similar in both age groups (p=0.9018). The adult group presented an average of
      10,286 +/- 2,308 myelinic fibers, and the elderly group presented an average of
      10,141 +/- 1,590 myelinic fibers. A bimodal distribution of the myelinic fibers
      was observed, with a significant peak on the 9 microm fibers, and another smaller
      peak on the 2 microm fibers. CONCLUSION: The intraperineural area and the total
      number of myelinic fibers of the right hypoglossal nerve are similar in both age
      groups.

PMID- 16612514
TI  - Mandibular fracture: analysis of 293 patients treated in the Hospital of Clinics,
      Federal University of Uberlandia.
AB  - Mandibular fracture is the second most common facial fracture and there has been
      a significant increase in number of cases in the last years. Misidentification
      and inadequate treatment can take to permanent aesthetic or functional deformity.
      AIM: Evaluate cases of mandibular fracture reduction in the Hospital of Clinics
      of the Federal University of Uberlandia, from January of 1974 to December of
      2002. STUDY DESIGN: Historical cohort. PATIENT AND METHOD: Two hundred and ninety
      three cases of reduction of mandibular fractures were retrospectively analyzed
      according to factors related to: patient, trauma, signs and symptoms, and
      surgical treatment. RESULTS: There has been a clear tendency of increase of the
      number of mandibular fractures along the years. There was higher prevalence in
      male (4:1), with occurrence peak between 20 to 29 years old. The principal causes
      of fracture in this study were traffic accidents and violence, representing
      72.4%. One hundred and thirty-five patients presented only one fracture. The most
      injured sites were, in decreasing order, symphysis, condyle, angle, body, ramus,
      and coronoid. We performed closed reduction (28), open reduction (213) and
      association of the two (11 patients); 56.8% of the patients were treated within
      the first 3 days; and, 50.4% were discharged from the hospital until the first
      postoperative day. About 10% of the patients presented complications, being
      osteomyelitis the most frequent one. CONCLUSION: The incidence of mandibular
      fractures was remarkably larger in the male sex, during the third decade of life.
      The most common cause was traffic accident, and symphysis and condyle were the
      most injured sites. Isolated fractures occurred in over half of the cases. Most
      of the patients were treated in the first three days and were discharged until
      the first postoperative visit. Closed reduction was the treatment most commonly
      employed. The most frequent complication was osteomyelitis.

PMID- 16612515
TI  - Application of botulinum toxin to reduce the saliva in patients with amyotrophic
      lateral sclerosis.
AB  - AIM: To demonstrate the effect of local application of Botox(R) in patients with
      amyotrophic lateral sclerosis (ALS), following our 2002 institutional protocol of
      sialorrhea treatment. STUDY DESIGN: Clinical prospective. MATERIAL AND METHOD:
      Five patients with ALS assisted at Clinic of Otolaryngology of AACD (Associacao
      de Assistencia a Crianca Deficiente). They were all submitted to local
      application of Botox in salivary glands and followed up for a year. The protocol
      consisted of clinical questionnaire about the inability of swallowing saliva and
      its repercussions in quality of life. Patients were submitted to previous
      odontological treatment, had intolerance to the adverse effects of anti
      cholinergic agents and had not used Botox for at least six months. The
      application was guided by ultrasound and the doses were 30U in one point for
      submandibular gland, and 20U in two points for each parotid gland, after topic
      anesthetic with prilocaine. RESULTS: Five patients with ALS with sialorrhea, aged
      45 to 59 years, were submitted to Botox salivary glands application. We observed
      that the symptoms of sialorrhea changed dramatically in four patients. Three
      patients stayed almost four months without complaints with repercussion in
      quality of life. No patient presented local or systemic effects with local
      injection of Botox.

PMID- 16612516
TI  - Infantile recurrent parotitis: follow up study of five cases and literature
      review.
AB  - Recurrent parotitis (RP) is defined as recurrent parotid inflammation, generally
      associated with non-obstructive sialectasis of the parotid gland. It is a rare
      condition, and its etiology remains an enigma. AIM: The purposes of the present
      study were (1) to relate the follow up of five RP cases; (2) to examine the role
      of sialography and ultrasound in diagnosis and follow up; and (3) to make a
      literature review. STUDY DESIGN: Series review. MATERIAL AND METHOD: We reviewed
      all recurrent parotitis cases from the files of the Otolaryngology Division at
      University of Sao Paulo, Brazil. The criteria for inclusion were at least two
      years of evolution and more than one year and a half follow-up in our service. We
      included five children in the study. Sialography was performed in the first
      evaluation and sonography was executed annually. Recurrent parotitis showed male
      predominance, and affected mainly children between the ages of 3 and 6. Frequency
      of crisis improved with time in all cases. Sialography showed sialectasis aspect
      in the affected glands and sonographic exams demonstrated hypoechoic and
      heterogeneous internal echoes. One case showed regression of ultrasound changes
      after clinical improvement.

PMID- 16612517
TI  - Vestibular folds configuration in vocal nodule.
AB  - Vocal nodules are among the most common laryngopathies that cause vocal
      functional disorders. The voice production mechanism is complex and demand
      interaction of different systems of the human body. The physiological role of the
      vocal folds as the glottic sound source is evident, however, there is no
      consensus regarding the vestibular folds' participation/influence in phonation.
      AIM: To verify if there is difference in the bidimensional configuration of the
      vestibular folds between two distinct groups of women, one with the diagnosis of
      vocal nodules and the other without vocal complaints and vocal fold lesions.
      STUDY DESIGN: Clinical with transversal cohort. MATERIAL AND METHOD: Ninety-six
      laryngeal images were evaluated, 48 from individuals without vocal complaints and
      48 from patients with the diagnosis of vocal nodules. Angles were obtained and
      bilaterally measured in single frames of the vestibular folds during sustained
      phonation and those structures were morphologically classified as concave, linear
      or convex. RESULTS: Among the 96 vestibular folds evaluated in each group, there
      was predominance of the concave form, followed by the linear and the convex ones.
      In the control group, there was a single convex vestibular fold, 27 were linear
      and 68 were concave folds. In the group of vocal nodules, 8 were convex, 15 were
      linear and 73 were concave folds. However, the differences among groups were not
      statistically significant as well as those among the angles, whose average
      measures were proven quite similar. CONCLUSION: In the female gender, the
      vestibular folds presented similar behavior regarding the morphology in both
      patients with vocal nodules and women without vocal complaints.

PMID- 16612518
TI  - Analysis of fundamental frequency, jitter, shimmer and vocal intensity in
      children with phonological disorders.
AB  - Phonological Disorder is a disturbance of primary manifestation of undefined
      causes that makes speech become unintelligible. The analysis of vocal parameters
      becomes important in the process of diagnosis of this disorder, since voice
      disorders could interfere in the production of speech sounds. AIM: The objective
      of this study was to verify vocal characteristics related to the intensity and
      fundamental frequency--F0--and their disturbance indexes--jitter and shimmer--in
      children with phonological disorders. STUDY DESIGN: Clinical prospective with
      transversal cohort. MATERIAL AND METHOD: There were 40 children, 20 of them with
      phonological disorders and 20 with no speech and language disturbances.
      Phonological exams with the ABFW infantile language test and spontaneous speech
      were applied. The Computer Speech Lab was used to record and perform acoustic
      analyses of the vowels /a/, /e/, /i/, through the vocal parameters: fundamental
      frequency, intensity, jitter and shimmer. RESULTS: F0--vowel /e/ was smaller, on
      average, in the Phonological Disorder Group and it was 126 Hz in the Control
      Group. To shimmer and jitter there was no evidence that the means of the
      Phonological Disorder Group were different from the ones of the Control Group (p=
      0.191, p= 0.865, respectively). As for intensity, there was evidence that the
      average did not differ in the Phonological Disorder Group and the Control Group
      (p= 0.002). CONCLUSION: The frequency of the vowel /e/ was smaller in the
      Phonological Disorder Group. There was difference between the two groups
      regarding the means of intensity of vowels /a/, /e/ and /i/, smaller in the
      Phonological Disorder Group. No differences between the groups were found
      regarding the averages of jitter and shimmer.

PMID- 16612519
TI  - Evaluation of Brazilian web site information on allergic rhinitis.
AB  - Nowadays, the World Wide Web (Internet) is an information source for non-experts
      and physicians. AIM: To evaluate, based on ethical principles, Brazilian web
      sites information about "allergic rhinitis". Allergic rhinitis is a very common
      disease, effecting more than 10% of the general population, leading to decrease
      in quality of life. STUDY DESIGN: Review. MATERIAL AND METHOD: We performed the
      evaluation of 173 Brazilian web sites, which were obtained from four search
      engines (Google, Yahoo, AltaVista and Radar Uol). The web sites were evaluated
      according to the Manual of Ethical Principles, Regional Council of Medicine of
      the state of Sao Paulo (CREMESP), regarding transparency, honesty, quality,
      privacy, medical ethics, informed consent, responsibility and origin. RESULTS:
      Among the analyzed web sites, 149 (86.1%) were not in accordance with the Manual
      of Ethical Principles of Regional Council of Medicine of the state of Sao Paulo
      (CREMESP). According to the analyzed items, the irregularities that were found
      were quality (84.4%), privacy (46.2%), honesty (18.5%), informed consent (15.6%),
      responsibility and origin (13.9%), transparency (12.1%), medical ethics (2.3%).
      There was inaccurate information in 24.3% of the analyzed sites. CONCLUSIONS: The
      majority of the websites regarding allergic rhinitis are not in accordance with
      the ethical principles of CREMESP. In general, the quality of a great part of the
      Brazilian web sites that address "allergic rhinitis", and the quality of the
      information disseminated by them, are insufficient to satisfy doctors and
      patients.

PMID- 16612520
TI  - Evaluation of inspiratory pressure in children with enlarged tonsils and
      adenoids.
AB  - Children with enlarged tonsils and adenoids usually present breathing
      abnormalities such as snoring, mouth breathing and sleep apnea. It is known that
      upper airway obstruction and consequent mouth breathing may result in pulmonary
      diseases. AIM: The goal of this preliminary study was to evaluate the inspiratory
      pressure in children with upper airway obstruction due to enlarged tonsils. STUDY
      DESIGN: Clinical with transversal cohort. MATERIAL AND METHOD: We evaluated 37
      children (4-3 years old, female/male) with enlarged tonsils who would be
      submitted to a T&A surgery in the Department of Otolaryngology, Medical School,
      University of Sao Paulo, from October 2002 to March 2003. The control group
      comprised 28 children without tonsillar disease submitted to the same tests.
      Inspiratory pressure was obtained using a manometer and vacuum meter. RESULTS: We
      could observe lower inspiratory pressures in children with upper airway
      obstruction. The mean of inspiratory pressure in the upper airway obstruction
      group was 14.607 cm/H2O and in the control group was of 27.580 cm/H2O.
      CONCLUSIONS: Enlarged tonsils and adenoids were associated with poor inspiratory
      pressure, resulting in increased breathing effort and work of the involved
      muscles.

PMID- 16612521
TI  - Chronic rhinosinusitis in HIV-infected patients: radiological and clinical
      evaluation.
AB  - The advent of protease inhibitors, which enhances the survival rate of HIV
      infected individuals, leads patients to search for otorhinolaryngologists, as 40
      70% of them may present some sort of otorhinolaryngological disorder. AIM: We
      aimed at comparing the CT scan findings and the nasosinusal complaints of HIV
      infected and AIDS patients with clinical diagnosis of chronic rhinosinusitis. The
      literature on the subject is revised and discussed. STUDY DESIGN: Clinical
      prospective with transversal cohort. MATERIAL AND METHODS: Prospectively, 39
      patients with chronic rhinosinusitis, in use of antiretroviral therapy, were
      included in the present study and divided into two groups: patients with
      diagnosis of AIDS (group I) and those infected by HIV (group II). Clinical and
      laboratorial assessments, with CD4+ cell count and CT evaluation, were performed
      and compared among groups I and II. RESULTS: Group I and II presented mean CD4+
      cell count of 118 cells/10-9l and 377 cells/10-9l, respectively. Comparison of
      the tomographic findings by the Lund-Mackay staging system presented a score of
      12 for group I and 5.63 (pd" 0.001) for group II. Fever and postnasal discharge
      were more prevalent in group I (pd" 0.001). CONCLUSIONS: In our Service,
      prevalence of chronic rhinosinusitis in HIV-infected patients was 12%. AIDS
      patients had a higher incidence of fever and postnasal discharge than those of
      group II. Moreover, extensive radiological findings were prevalent in patients
      with AIDS (group I) than in HIV-infected individuals (group II).

PMID- 16612522
TI  - A ten-year historic study of paranasal cavity endoscopy in patients with Leprosy.
AB  - Leprosy is an infectious condition that has a chronic evolution caused by the
      Mycobacterium leprae. It very often attacks the nasal cavities mucosa independent
      of its clinical form, even before skin lesions or lesions to other parts of the
      body arise, in the presence or not of clinical complaints. AIM: To show the
      efficiency of nasal endoscopy to identify endonasal mucosa lesions and the
      importance of the Otorhinolaryngologist in the diagnosis and follow-up of Leprosy
      patients. STUDY DESIGN: Clinical history study. MATERIAL AND METHOD: A historic
      study was performed with 173 patient's records without previous treatment from
      1990 to 2000 at the Otorhinolaryngology Services, Instituto de Pesquisas Clinicas
      Hospital Evandro Chagas, Fiocruz. RESULTS: All of the patients showed nasal
      lesions, 121 with and 52 without clinical complaints. DISCUSSION: Nasal cavities
      endoscopy exam enabled early identification of the mucosa alteration in Leprosy
      patients as well as how to identify the evolution of the lesions. This type of
      exam also helps to establish local treatment. CONCLUSION: The evaluation and
      follow-up of Leprosy patients by the Otorhinolaryngologist in a multidisciplinary
      team are justified and offer the patient early diagnosis and specific treatment.

PMID- 16612523
TI  - Tinnitus treatment with acamprosate: double-blind study.
AB  - Nowadays, the treatment of tinnitus is still a great challenge for the
      otolaryngologists. Many facts remain unknown in its pathophysiology, leading to
      many different therapies, with irregular results. Acamprosate is a drug used in
      alcoholism treatment, due to its regulating effects in glutamatergic and GABA
      neurotransmission, and has never been used before in the treatment of tinnitus
      AIM: To evaluate efficacy and safety of the acamprosate in the treatment of
      sensorineural tinnitus. STUDY DESIGN: Randomized clinical trial. MATERIAL AND
      METHOD: 50 patients with sensorineural tinnitus were divided into two groups: 25
      received acamprosate and 25 placebo, for a period of 3 months, in a prospective
      double-blind study, being analyzed for its efficacy and safety by the subjective
      score from 1 to 10 given by the patient. RESULTS: We found a high index of
      success in the relief of tinnitus, about 86.9%. In 47.8% of the cases we found
      more than 50% relief. The incidence of side effects was low, 12%, all of them
      mild. CONCLUSION: Acamprosate, a drug used in the treatment of alcoholism, is a
      safe and successful alternative for sensorineural tinnitus' treatment.

PMID- 16612524
TI  - Reliability of recognition thresholds of sentences in quiet and in noise.
AB  - A larger number of research studies has been performed with different people and
      objectives and have shown that the sentence recognition test in noise is the best
      instrument to evaluate individuals' daily communication. However, we believe
      these tests are not applied so frequently because they require a lot of research
      to establish the parameters and variables related to their application and
      interpretation of the results. AIM: To check the reliability of the recognition
      threshold of the sentences in quiet and in noise for a group of young normal
      listeners. STUDY DESIGN: Transversal cohort. MATERIAL AND METHOD: The group
      comprised 40 subjects, 20 males and 20 females, with ages between 18 and 28 and
      all of them with normal hearing threshold. First, we applied the Basic
      Audiological Evaluation and after this, the Sentence Recognition Threshold test
      in quiet (LRSS) and in noise (LRSR). The sentences and the noise (fixed in 65 dB
      HL) were presented monoaurally, by earphones through "ascending-descending"
      strategy. The test and retest were done in different evaluation sessions, with an
      interval of seven days between them, respecting the same hour of evaluation.
      RESULTS: The results showed strong positive statistically significant correlation
      between the test and retest of LRSS, both for right ear (r = 0.6107) and left ear
      (r = 0.5853), as S/N ratio, for right ear (r = 0.5711) and for left ear (r =
      0.5867) for the assessed individuals. CONCLUSION: In the end of this study, we
      concluded that LRSS and S/N ratio obtained from the Portuguese Sentence List Test
      showed to be highly reliable, with strong positive correlation when compared to
      the results obtained in different sessions of evaluation in a group of young
      normal listeners.

PMID- 16612525
TI  - Clinical, etiological and progression factors of hearing in sudden deafness.
AB  - Out of the many forms of therapy for sudden deafness, some require
      hospitalization and present significant risks. AIM: This prospective study
      analyzes etiology and evolution in cases of sudden deafness (SD) where outpatient
      oral treatment was used. STUDY DESIGN: Clinical with transversal cohort. MATERIAL
      AND METHOD: Forty cases of sudden hearing loss were followed for at least one
      year. All were submitted to initial clinical evaluation, auditory tests, routine
      blood analysis, and magnetic resonance imaging. All received initial treatment
      with pentoxifylline and prednisone. RESULTS: 45% (n=18) presented normal auditory
      thresholds, 40% (n=16) showed some improvement in hearing, 15% (n=6) maintained
      initial hearing level. Nine cases (22.5%) presented clinical conditions possibly
      implicated in hearing loss (viral infection, immunomediated hearing loss,
      vascular disorders, and so on); three (7.5%) had cerebellopontine tumors.
      Evolution of hearing in these 12 cases with presumed etiology presented no
      differences from hearing in the 28 cases without any known etiological factor.
      Clinical treatment within the first seven days was the only statistically
      significantly different condition in patients who improved hearing. CONCLUSIONS:
      An objective search for etiological bases should be conducted in any case of
      acute sensorineural hearing loss. The presence of cerebellopontine tumors in 7.5%
      of cases of SD, among other treated causes, justifies a thorough clinical
      investigation in these patients. Overall good evolution of hearing was observed
      in 67.5% of cases of SD, regardless of its etiology. Therapy within the first
      seven days of SD was significantly related to better outcomes in hearing.

PMID- 16612526
TI  - Equivalent volume: study in subjects with chronic otitis media.
AB  - The equivalent ear canal volume ranges from 0.3 ml to 1.0 ml in children and from
      0.65 to 1.75 ml in adults. In subjects with chronic otitis media these values can
      be different, according to the disease status. AIM: To study the equivalent ear
      canal volume in 52 ears of patients with chronic otitis media with and without
      active infection. STUDY DESIGN: Clinical prospective with transversal cohort.
      MATERIAL AND METHOD: The equivalent ear canal volume was obtained from 52 ears
      diagnosed with chronic otitis media with and without active infection and in age
      and gender matched control group. The study group with active infection was
      evaluated before and after clinical treatment. RESULTS: Equivalent ear canal
      volume mean for the studied groups with and without infection and for the control
      group was 2.86 ml; 1.42 ml and 0.80 ml, respectively. The equivalent ear canal
      volume mean for the study group with infection prior and post clinical treatment
      was 1.42 ml and 1.82 ml, respectively. CONCLUSIONS: The equivalent ear canal
      volume mean was higher in patients with chronic otitis media. We did not observe
      variation of equivalent ear canal volume before and after clinical treatment.

PMID- 16612527
TI  - Intracranial complications of chronic suppurative otitis media in children.
AB  - In spite of significant decrease after antibiotic advent, intracranial
      complications of otitis media still represent a challenging situation owing to
      its high mortality rate (36%). The most common presentations are meningitis,
      cerebral abscess, extradural abscess and lateral sinus thrombophlebitis. For
      early management, it is necessary to have a high index of suspicion. It is
      important to identify non-typical cases because they might be masqueraded by
      antibiotic use. AIM: We present six cases of intracranial complications due to
      otitis media in children and adolescents at Complexo Hospitalar Santa Casa de
      Porto Alegre for the past two years. STUDY DESIGN: Series review.

PMID- 16612528
TI  - Evaluation of satisfaction measures of analog and digital hearing aid users.
AB  - AIM: The objective of this study was to investigate the satisfaction measure of
      analog and digital hearing aid users. STUDY DESIGN: Clinical with transversal
      cohort. MATERIAL AND METHOD: Among the 40 interviewed subjects, 20 were analog
      hearing aid users (Group I) and 20 were digital hearing aid users (Group II). The
      subjects had mild to moderate sensorineural hearing impairment, and were aged 45
      to 95 years old. RESULTS: The inventory of self-assessment completed by the
      hearing aid users was the International Outcome Inventory for Hearing Aids (IOI
      HA--Portuguese version) proposed by Cox et al. (2002). The users of Group II used
      the hearing aid longer every day than the analog hearing aid users (Group I). The
      users of Group II have fewer difficulties with the amplification at some
      situations than the users of Group I. Despite the fact that users of Group I have
      presented mode deficit than the users of Group II, the results agree that all the
      subjects reported satisfaction with their hearing aids.

PMID- 16612529
TI  - Neural response telemetry measures in patients implanted with Nucleus 24.
AB  - Cochlear implantation has been recommended for children under 24 months of age.
      The use of objective measures is needed to help speech processor programming. The
      electrically evoked compound potential (EAP), which can be assessed by neural
      response telemetry (NRT), is one of those objective measures. AIM: to determine
      how often the EAP can be recorded by NRT system during surgery and to describe
      the responses. STUDY DESIGN: Clinical with transversal cohort. MATERIAL AND
      METHOD: The impedances and NRT were measured in a group of 17 Nucleus 24 implant
      users. The responses were analyzed and compared to the etiology, hearing loss
      duration and electrode array position. RESULTS: The EAP was easily recorded in
      the apical electrodes and, in otosclerosis and meningitis cases the EAP threshold
      was higher than in the other etiology cases. CONCLUSIONS: The NRT can be found in
      82% of the cases during surgery. The responses obtained may vary according to
      etiology and the position of electrodes along the cochlea.

PMID- 16612530
TI  - Otomicroscopic and histologic findings of induced myringosclerosis in rats: a
      critical study of an experimental model.
AB  - Myringosclerosis is characterized by hyaline changes of the lamina propria of the
      tympanic membrane. Experimental studies have used otomicroscopy or histology to
      evaluate myringosclerosis in animals, but they do not correlate precisely these
      two methods. AIM: The present study evaluates the accuracy of otomicroscopy in
      the diagnosis of myringosclerosis in rats. STUDY DESIGN: Experimental. MATERIAL
      AND METHOD: Myringosclerosis was induced by transtympanic inoculation of
      Streptococcus pneumoniae in 25 Wistar rats, which were examined weekly through
      otomicroscopy and sacrificed after eight weeks for histologic study of their
      tympanic membranes. RESULTS: From the comparison of the otomicroscopic data in
      relation to the histologic findings, we could observe sensibility of 80% and
      specificity of 75% for the otomicroscopy. CONCLUSION: Considering the results in
      this study, otomicroscopy did not represent a good method to evaluate
      myringosclerosis in this experimental model.

PMID- 16612531
TI  - Anatomic and radiograph study of the persistence of Foramen of Huschke.
AB  - AIM: The aim of this study is to assess and locate the Foramen of Huschke. STUDY
      DESIGN: Anatomical. MATERIAL AND METHOD: Using contrast material like gutta
      percha and barium sulfate, through extraoral radiographs, such as panoramic,
      submental vertex and corrected sagittal linear Temporal Mandibular Joint
      tomograms in four skulls where we clinically checked the existence of foramen of
      Huschke. RESULTS: The results proved that the foramen of Huschke can be observed
      in skulls submitted to contrast using radiographic techniques.

PMID- 16612532
TI  - Oculomotricity in childhood: is the normal range the same as in adults?
AB  - The study of oculomotricity is done by the evaluation of three systems: saccade
      eye movements (MOS), optokinetic nystagmus (NO) and smooth pursuit eye movement
      (MORL). The joint action of these three systems allows the visual field's
      establishment in different movement situations. AIM: To compare the value of
      oculomotricity in normal adults and children to confirm, or not if it is viable
      to use the same parameters of adults normality to children's exams
      interpretation. STUDY DESIGN: Clinical with transversal cohort. MATERIAL AND
      METHOD: We studied MOS, NO and MORL in 50 normal children and in 35 adults and
      the results were compared by the t Student test. RESULTS: The data analysis
      showed significant difference between children and adults (significance at level
      +/- = 0.05) DISCUSSION: In the literature we have found evidence that
      myelinization of the vestibular pathways happen at about 16 weeks and the
      pyramidal tracts, at 24 months. Oculomotricity is finished at this time. Other
      papers describe the importance of these tests in the diagnostic of neurological
      diseases, visual alterations and as predictors of the risk of schizophrenia
      development but they do not report the normal range in children. In our study we
      found increased latency of MOS, increase in gain of NO, reduction in gain and
      increase in the distortion of MORL in children if compared to adults, which is in
      accordance with the literature. These alterations can be explained by the low
      attention during the tests and the immaturity of ocular movements' control in
      children. CONCLUSION: Therefore, the establishment of a parameter of normality to
      the oculomotricity in childhood is necessary for the correct analysis of the
      oculography to avoid misinterpretation of the exam.

PMID- 16612533
TI  - Antibiotic use in tonsillectomies: therapeutic or prophylactic? Required or
      excessive?
AB  - Adenotonsillectomy is one of the most commonly performed surgeries in the
      pediatric and young adult populations. The postoperative morbidity of this
      surgical procedure is often significant, including odynophagia, dysphagia, fever,
      halitosis, loss of weight and reduced oral intake. After tonsillectomy, with or
      without adenoidectomy, the colonization of the open tonsillar fossae by the
      bacterial population of the oral cavity would cause an exacerbation of the local
      inflammatory response worsening postoperative pain. The hypothesis that a
      reduction of the bacterial population of an open surgical wound could minimize
      the local inflammation, stimulate the healing process and hasten recovery
      triggered a considerable number of studies addressing the relation between the
      use of perioperative antibiotics and postoperative morbidity of
      adenotonsillectomy. In spite of the fact that those studies claim to perform an
      assessment of the surgical prophylactic use of antibiotics, their outline is not
      in compliance with the worldwide-accepted principles of surgical antibiotic
      prophylaxis. By performing a critical review of the literature, the authors
      discuss the advantages and disadvantages of using antibiotics in tonsillectomies
      or adenotonsillectomies, as well as the most appropriate definition for its
      utilization.

PMID- 16612534
TI  - Endoscopic posterior mesorectal resection after transanal local excision of T1
      carcinomas of the lower third of the rectum.
AB  - PURPOSE: The rectum-sparing transanal local excision is a well-established
      treatment of T1 carcinomas of the lower third of the rectum. A potentially
      increased locoregional recurrence rate by this procedure is tolerated because of
      the high morbidity and mortality risk of transabdominal rectal resection.
      Dorsoposterior extraperitoneal pelviscopy makes it possible to remove the
      relevant lymphatic drainage of the lower third of the rectum minimally
      invasively, in the sense of a rectum-sparing endoscopic posterior mesorectal
      resection. It has to be considered whether endoscopic posterior mesorectal
      resection in combination with transanal local excision allows for local
      radicality and an adequate tumor staging in T1 carcinomas of the lower third of
      the rectum, in terms of better-directed therapy planning compared with transanal
      local excision alone. METHODS: We operated on 11 consecutive patients with T1
      carcinomas of the lower third of the rectum by transanal local excision in
      combination with endoscopic posterior mesorectal resection as a two-stage
      procedure in the period from 1998 to 2005. RESULTS: It was possible to perform a
      complete excision of the primary and to resect the posterior part of the
      mesorectum in all cases. Postoperative morbidity consisted of two transient
      neurologic complications and a pulmonary embolism. There was no mortality.
      Histologic analysis revealed a median of eight (range, 4-20) lymph nodes. Two
      patients diagnosed with lymph-node metastases received adjuvant
      radiochemotherapy. After a median follow-up of 48 (range, 4-60) months, there was
      no evidence for locoregional recurrence. In one patient liver metastasis was
      detected eight months postoperatively. CONCLUSIONS: Radical excision of the
      primary tumor and an adequate tumor staging in T1 carcinomas of the lower third
      of the rectum seems to be achievable by means of transanal local excision and
      endoscopic posterior mesorectal resection.

PMID- 16612535
TI  - Processed pseudogenes, processed genes, and spontaneous mutations in the
      Arabidopsis genome.
AB  - We identified 411 processed sequences in the Arabidopsis thaliana genome based on
      the fact that they have lost their intron(s) and have a length that is at least
      95% of the length of the gene that gave rise to them. These sequences were
      generated by 230 different genes and clearly originated from retrotranspositons
      events because most of them (91%) have a poly(A)-tail. They are composed of 376
      sequences with frame shifts and/or premature stop codons (processed pseudogenes)
      and 35 sequences without disablements (processed genes). Eleven of these
      processed genes are likely functional retrotransposed genes because they have low
      Ka/Ks ratios and high Ks values, and their sequences match numerous Arabidopsis
      ESTs. Processed sequences are mostly randomly distributed in the Arabidopsis
      genome and their rate of accumulation has steadily been decreasing since it
      peaked some 50 MYA. In contrast with the situation observed in mammals, the
      processed sequences found in the Arabidopsis genome originate from genes with
      high copy numbers and not from highly expressed genes. The patterns of
      spontaneous mutations in Arabidopsis are slightly different than those of mammals
      but are similar to those observed in Drosophila. This suggests that methylated
      cytosine deamination is less frequent in Arabidopsis than in mammals.

PMID- 16612536
TI  - Evolution of structural shape in bacterial globin-related proteins.
AB  - The globin family of proteins has a characteristic structural pattern of helix
      interactions that nonetheless exhibits some variation. A simplified model for
      globin structural evolution was developed in which protein shape evolved by
      random change of contacts between helices. A conserved globin domain of 15
      bacterial proteins representing four structural families was studied. Using a
      parsimony approach ancestral structural states could be reconstructed. The
      distribution of number of contact changes per site for a fixed topology tree fit
      a gamma distribution. Homoplasy was high, with multiple changes per site and no
      support for an invariant class of residue-residue contacts. Contacts changed more
      slowly than sequence. A phylogenetic reconstruction using a distance measure
      based on the proportion of shared contacts was generally consistent with a
      sequence-based phylogeny but not highly resolved. Contact pattern convergence
      between members of different globin family proteins could not be detected.
      Simulation studies indicated the convergence test was sensitive enough to have
      detected convergence involving only 10% of the contacts, suggesting a limit on
      the extent of selection for a specific contact pattern. Contact site methods may
      provide additional approaches to study the relationship between protein structure
      and sequence evolution.

PMID- 16612537
TI  - The repetitive DNA elements called CRISPRs and their associated genes: evidence
      of horizontal transfer among prokaryotes.
AB  - We have found direct DNA repeats 21-47 bp in length interspersed with
      nonrepetitive sequences of similar length, or clustered regularly interspaced
      short palindromic repeats (CRISPRs) in a wide range of diverse prokaryotes,
      including many Archaeal and Eubacterial species. A number of cas, CRISPR
      associated genes have also been characterized in many of the same organisms.
      Phylogenetic analysis of these cas genes suggests that the CRISPR loci have been
      propagated via HGT, horizontal gene transfer. We suggest a mechanism by which
      this HGT has occurred, namely, that the CRISPR loci can be carried between cells
      on megaplasmids > or = 40 kb in length.

PMID- 16612538
TI  - A sequential "2-1-3" model of genetic code evolution that explains codon
      constraints.

PMID- 16612539
TI  - Sauria SINEs: Novel short interspersed retroposable elements that are widespread
      in reptile genomes.
AB  - SINEs are short interspersed retrotransposable elements that invade new genomic
      sites. Their retrotransposition depends on reverse transcriptase and endonuclease
      activities encoded by partner LINEs (long interspersed elements). Recent genomic
      research has demonstrated that retroposons account for at least 40% of the human
      genome. Hitherto, more than 30 families of SINEs have been characterized in
      mammalian genomes, comprising approximately 4600 extant species; the distribution
      and extent of SINEs in reptilian genomes, however, are poorly documented. With
      more than 7400 species of lizards and snakes, Squamata constitutes the largest
      and most diverse group of living reptiles. We have discovered and characterized a
      novel SINE family, Sauria SINEs, whose members are widely distributed among
      genomes of lizards, snakes, and tuataras. Sauria SINEs comprise a 5' tRNA-related
      region, a tRNA-unrelated region, and a 3' tail region (containing short tandem
      repeats) derived from LINEs. We distinguished eight Sauria SINE subfamilies in
      genomes of four major squamate lineages and investigated their evolutionary
      relationships. Our data illustrate the overall efficacy of Sauria SINEs as novel
      retrotransposable markers for elucidation of squamate evolutionary history. We
      show that all Sauria SINEs share an identical 3' sequence with Bov-B LINEs and
      propose that they utilize the enzymatic machinery of Bov-B LINEs for their own
      retrotransposition. This finding, along with the ubiquity of Bov-B LINEs
      previously demonstrated in squamate genomes, suggests that these LINEs have been
      an active partner of Sauria SINEs since this SINE family was generated more than
      200 million years ago.

PMID- 16612540
TI  - Rapid adaptive evolution of the tumor suppressor gene Pten in an insect lineage.
AB  - The Pten gene was initially identified in humans as a tumor suppressor. It has
      since been shown to play important roles in the control of cell size, cell
      motility, apoptosis, and organ size, and it has also been implicated in aging.
      Pten is highly conserved among organisms as diverse as nematodes, insects, and
      vertebrates. In contrast, a phylogenetic analysis by maximum likelihood of a 133
      amino acid region showed an average nonsynonymous-to-synonymous rate ratio of
      10.4 for Pten in the lineage leading to parasitoid wasps of the Nasonia genus,
      indicating very strong positive selection. A previous study identified Pten as a
      potential QTL candidate gene for differences in male wing size in Nasonia. Most
      of the amino acid replacements that occurred in the Nasonia lineage cluster in a
      small region of the protein surface, suggesting that they might be involved in an
      interaction between Pten and another protein. The phenotypic changes due to Pten
      are not yet known, although it is not associated with known differences in male
      wing size. Introgression of Pten from one species to another does affect
      longevity, but a causal relationship is not established.

PMID- 16612542
TI  - The histidine operon is ancient.

PMID- 16612541
TI  - Selection for chromosome architecture in bacteria.
AB  - Bacterial chromosomes are immense polymers whose faithful replication and
      segregation are crucial to cell survival. The ability of proteins such as FtsK to
      move unidirectionally toward the replication terminus, and direct DNA
      translocation into the appropriate daughter cell during cell division, requires
      that bacterial genomes maintain an architecture for the orderly replication and
      segregation of chromosomes. We suggest that proteins that locate the replication
      terminus exploit strand-biased sequences that are overrepresented on one DNA
      strand, and that selection increases with decreased distance to the replication
      terminus. We report a generalized method for detecting these architecture
      imparting sequences (AIMS) and have identified AIMS in nearly all bacterial
      genomes. Their increased abundance on leading strands and decreased abundance on
      lagging strands toward replication termini are not the result of changes in
      mutational bias; rather, they reflect a gradient of long-term positive selection
      for AIMS. The maintenance of the pattern of AIMS across the genomes of related
      bacteria independent of their positions within individual genes suggests a well
      conserved role in genome biology. The stable gradient of AIMS abundance from
      replication origin to terminus suggests that the replicore acts as a target of
      selection, where selection for chromosome architecture results in the maintenance
      of gene order and in the lack of high-frequency DNA inversion within replicores.

PMID- 16612543
TI  - A genomic comparison of faster-sex, faster-X, and faster-male evolution between
      Drosophila melanogaster and Drosophila pseudoobscura.
AB  - A genomic comparison of Drosophila melanogaster and Drosophila pseudoobscura
      provides a unique opportunity to investigate factors involved in sequence
      divergence. The chromosomal arrangements of these species include an autosomal
      segment in D. melanogaster which is homologous to part of the X chromosome in D.
      pseudoobscura. Using orthologues to calculate rates of nonsynonymous (d(N))
      substitutions, we found genes on the X chromosome to be significantly more
      diverged than those on the autosomes, but it is not true for segment 3L-XR which
      is autosomal in D. melanogaster (3L) and X-linked in D. pseudoobscura (XR). We
      also found that the median d(N) values for genes having reproductive functions in
      either the male, the female, or both sexes are higher than those for sequences
      without reproductive function and even higher for sequences involved in male
      specific function. These estimates of divergence for male sex-related sequences
      are most likely underestimates, as the very rapidly evolving reproductive genes
      would tend to lose homology sooner and thus not be included in the comparison of
      orthologues. We also noticed a high proportion of male reproductive genes among
      the othologous genes with the highest rates of d(N). Reproductive genes with and
      without an orthologue in D. pseudoobscura were compared among D. melanogaster, D.
      simulans, and D. yakuba and it was found that there were in fact higher rates of
      divergence in the group without a D. pseudoobscura orthologue. These results,
      from widely separated taxa, bolster the thesis that sexual system genes
      experience accelerated rates of change in comparison to nonsexual genes in
      evolution and speciation.

PMID- 16612544
TI  - Twinkle, the mitochondrial replicative DNA helicase, is widespread in the
      eukaryotic radiation and may also be the mitochondrial DNA primase in most
      eukaryotes.
AB  - Recently, the human protein responsible for replicative mtDNA helicase activity
      was identified and designated Twinkle. Twinkle has been implicated in autosomal
      dominant progressive external ophthalmoplegia (adPEO), a mitochondrial disorder
      characterized by mtDNA deletions. The Twinkle protein appears to have evolved
      from an ancestor shared with the bifunctional primase-helicase found in the T-odd
      bacteriophages. However, the question has been raised as to whether human Twinkle
      possesses primase activity, due to amino acid sequence divergence and absence of
      a zinc-finger motif thought to play an integral role in DNA binding. To date, a
      primase protein participating in mtDNA replication has not been identified in any
      eukaryote. Here we investigate the wider phylogenetic distribution of Twinkle by
      surveying and analyzing data from ongoing EST and genome sequencing projects. We
      identify Twinkle homologues in representatives from five of six major eukaryotic
      assemblages ("supergroups") and present the sequence of the complete Twinkle gene
      from two members of Amoebozoa, a supergroup of amoeboid protists at the base of
      the opisthokont (fungal/metazoan) radiation. Notably, we identify conserved
      primase motifs including the zinc finger in all Twinkle sequences outside of
      Metazoa. Accordingly, we propose that Twinkle likely serves as the primase as
      well as the helicase for mtDNA replication in most eukaryotes whose genome
      encodes it, with the exception of Metazoa.

PMID- 16612545
TI  - Some aspects of E. coli promoter evolution observed in a molecular evolution
      experiment.
AB  - We devised a molecular evolution procedure to evolve E. coli promoter sequences
      and applied it to observe an arbitrary, nonfunctional sequence evolving into
      functional promoters. In the experiments, DNA sequence variations were generated
      with error-prone PCR and were inserted in the promoter region of the cat
      (chloramphenicol acetyl transferase) gene on a plasmid. Upon transforming the
      cells, functional promoters on the plasmid were selected according to the
      chloramphenicol resistance. Within a few cycles of mutation-selection, promoters
      emerged, and the sequences converged into a small number of groups. In the
      process, the extended minus 10 type of promoters emerged quickly, and small
      deletions were often involved in adjusting the length between the -35 and the -10
      elements. Our results also suggest a possible selection for promoter stability
      against mutation.

PMID- 16612546
TI  - Molecular organization of 5S rDNAs in Rajidae (Chondrichthyes): Structural
      features and evolution of piscine 5S rRNA genes and nontranscribed intergenic
      spacers.
AB  - The genomic and gene organisation of 5S rDNA clusters have been extensively
      characterized in bony fish and eukaryotes, providing general issues for
      understanding the molecular evolution of this multigene DNA family. By contrast,
      the 5S rDNA features have been rarely investigated in cartilaginous fish (only
      three species). Here, we provide evidence for a dual 5S rDNA gene system in the
      Rajidae by sequence analysis of the coding region (5S) and adjacent
      nontranscribed spacer (NTS) in five Mediterranean species of rays (Rajidae), and
      in a large number of piscine taxa including lampreys and bony fish. As documented
      in several bony fish, two functional 5S rDNA types were found here also in the
      rajid genome: a short one (I) and a long one (II), distinguished by distinct 5S
      and NTS sequences. That the ancestral piscine genome had these two 5S rDNA loci
      might be argued from the occurrence of homologous dual gene systems that exist in
      several fish taxa and from 5S phylogenetic relationships. An extensive analysis
      of NTS-II sequences of Rajidae and Dasyatidae revealed the occurrence of large
      simple sequence repeat (SSR) regions that are formed by microsatellite arrays.
      The localization and organization of SSR within the NTS-II are conserved in
      Rajiformes since the Upper Cretaceous. The direct correlation between the SSRs
      extension and the NTS length indicated that they might play a role in the
      maintenance of the larger 5S rDNA clusters in rays. The phylogenetic analysis
      indicated that NTS-II is a valuable systematic tool limited to distantly related
      taxa of Rajiformes.

PMID- 16612547
TI  - Molecular evolution of the periphilin gene in relation to human endogenous
      retrovirus m element.
AB  - HERV-M (human endogenous retrovirus M), related to the super family of HERV-K,
      has a methionine (M) tRNA primer-binding site, and is located within the
      periphilin gene on human chromosome 12q12. HERV-M has been integrated into the
      periphilin gene as the truncated form, 5'LTR-gag-pol-3'LTR. Polymerase chain
      reaction (PCR) and reverse transcription-polymerase chain reaction (RT-PCR)
      approaches were conducted to investigate its evolutionary origins. Interestingly,
      the insertion of retroelements in a common ancestor genome can make different
      transcript variants in different species. In the case of the periphilin gene,
      human (10 variants) and mouse (2 variants) lineages show different transcript
      variants. Insertion of HERV-M (variant 1-3) could affect the protein-coding
      region. Also, Alusq/x (variant 4-9) and L1ME4a (mammalian-wide subfamilies of
      LINE-1) (variant 10) in humans and SINE (short interspersed repetitive element)
      and RLTR15 (the mouse putative long terminal repeat) (variant 2) in mice could be
      driving forces in transcript diversification of the periphilin gene during
      mammalian evolution. The HERV-M derived transcripts (variant 1-3) were expressed
      in different human tissues, whereas they were not detected in crab-eating monkey
      and squirrel monkey tissues by RT-PCR amplification. Taken together, HERV-M seems
      to have been integrated into our common ancestor genome after the divergence of
      simians and prosimians, and then was actively expressed during hominoid
      evolution.

PMID- 16612548
TI  - Strong purifying selection on the Odysseus gene in two clades of sibling species
      of the Drosophila montium species subgroup.
AB  - The Odysseus (OdsH) gene was duplicated from its ancestral neuron-expressed gene,
      unc-4, and then evolved very rapidly under strong positive Darwinian selection as
      a speciation gene causing hybrid-male sterility between closely related species
      of the Drosophila simulans clade. Has OdsH also experienced similar positive
      selection between Drosophila sibling species other than those of the simulans
      clade? We cloned and sequenced OdsH and unc-4 from two clades of the Drosophila
      montium species subgroup, the Drosophila lini and the Drosophila kikkawai clades.
      The ratios of Ka/Ks for OdsH were remarkably low between sibling species of these
      two clades, suggesting that OdsH has been subjected to strong purifying selection
      in these two clades.

PMID- 16612549
TI  - Prevalence, extension and characteristics of fluid-fluid levels in bone and soft
      tissue tumors.
AB  - The purpose of this study was to determine the prevalence, extension and signal
      characteristics of fluid-fluid levels in a large series of 700 bone and 700 soft
      tissue tumors. Out of a multi-institutional database, MRI of 700 consecutive
      patients with a bone tumor and MRI of 700 consecutive patients with a soft tissue
      neoplasm were retrospectively reviewed for the presence of fluid-fluid levels.
      Extension (single, multiple and proportion of the lesion occupied by fluid-fluid
      levels) and signal characteristics on magnetic resonance imaging of fluid-fluid
      levels were determined. In all patients, pathologic correlation was available. Of
      700 patients with a bone tumor, 19 (10 male and 9 female; mean age, 29 years)
      presented with a fluid-fluid level (prevalence 2.7%). Multiple fluid-fluid levels
      occupying at least one half of the total volume of the lesion were found in the
      majority of patients. Diagnoses included aneurysmal bone cyst (ten cases),
      fibrous dysplasia (two cases), osteoblastoma (one case), simple bone cyst (one
      case), telangiectatic osteosarcoma (one case), "brown tumor" (one case),
      chondroblastoma (one case) and giant cell tumor (two cases). Of 700 patients with
      a soft tissue tumor, 20 (9 males and 11 females; mean age, 34 years) presented
      with a fluid-fluid level (prevalence 2.9%). Multiple fluid-fluid levels occupying
      at least one half of the total volume of the lesion were found in the majority of
      patients. Diagnoses included cavernous hemangioma (12 cases), synovial sarcoma (3
      cases), angiosarcoma (1 case), aneurysmal bone cyst of soft tissue (1 case),
      myxofibrosarcoma (1 case) and high-grade sarcoma "not otherwise specified" (2
      cases). In our series, the largest reported in the literature to the best of our
      knowledge, the presence of fluid-fluid levels is a rare finding with a prevalence
      of 2.7 and 2.9% in bone and soft tissue tumors, respectively. Fluid-fluid levels
      remain a non-specific finding and can occur in a wide range of bone and soft
      tissue tumors, both benign and malignant. Therefore, they cannot be considered
      diagnostic of any particular type of tumor, and the diagnosis should be made on
      the basis of other radiological and clinical findings.

PMID- 16612550
TI  - Application and assessment of a robust elastic motion correction algorithm to
      dynamic MRI.
AB  - The purpose of this study was to assess the performance of a new motion
      correction algorithm. Twenty-five dynamic MR mammography (MRM) data sets and 25
      contrast-enhanced three-dimensional peripheral MR angiographic (MRA) data sets
      which were affected by patient motion of varying severeness were selected
      retrospectively from routine examinations. Anonymized data were registered by a
      new experimental elastic motion correction algorithm. The algorithm works by
      computing a similarity measure for the two volumes that takes into account
      expected signal changes due to the presence of a contrast agent while penalizing
      other signal changes caused by patient motion. A conjugate gradient method is
      used to find the best possible set of motion parameters that maximizes the
      similarity measures across the entire volume. Images before and after correction
      were visually evaluated and scored by experienced radiologists with respect to
      reduction of motion, improvement of image quality, disappearance of existing
      lesions or creation of artifactual lesions. It was found that the correction
      improves image quality (76% for MRM and 96% for MRA) and diagnosability (60% for
      MRM and 96% for MRA).

PMID- 16612551
TI  - Analysis of the ear pulse oximeter waveform.
AB  - OBJECTIVE: For years researchers have been attempting to understand the
      relationship between central hemodynamics and the resulting peripheral waveforms.
      This study is designed to further understanding of the relationship between ear
      pulse oximeter waveforms, finger pulse oximeter waveforms and cardiac output
      (CO). It is hoped that with appropriate analysis of the peripheral waveforms,
      clues can be gained to help to optimize cardiac performance. METHODS: Part 1:
      Studying the effect of cold immersion test on plethysmographic waveforms. Part 2:
      Studying the correlation between ear and finger plethysmographic waveforms and
      (CO) during CABG surgery. The ear and finger plethysmographic waveforms were
      analyzed to determine amplitude, width, area, upstroke and downslope. The CO was
      measured using continuous PA catheter. Using multi-linear regression, ear
      plethysmographic waveforms, together with heart rate (HR), were used to determine
      the CO Agreement between the two methods of CO determination was assessed.
      RESULTS: Part 1: On contralateral hand immersion, all finger plethysmographic
      waveforms were reduced, there was no significant change seen in ear
      plethysmographic waveforms, except an increase in ear plethysmographic width.
      Part 2: Phase 1: Significant correlation detected between the ear
      plethysmographic width and other ear and finger plethysmographic waveforms. Phase
      2: The ear plethysmographic width had a significant correlation with the HR and
      CO. The correlation of the other ear plethysmographic waveforms with CO and HR
      are summarized (Table 5). Multi-linear regression analysis was done and the best
      fit equation was found to be: CO=8.084 - 14.248 x Ear width + 0.03 x HR+ 92.322 x
      Ear down slope+0.027 x Ear Area Using Bland & Altman, the bias was (0.05 L) but
      the precision (2.46) is large to be clinically accepted. CONCLUSION: The ear is
      relatively immune to vasoconstrictive challenges which make ear plethysmographic
      waveforms a suitable monitor for central hemodynamic changes. The ear
      plethysmographic width has a good correlation with CO.

PMID- 16612552
TI  - Isolation and characterization of novel denitrifying alkalithermophiles, AT-1 and
      AT-2.
AB  - Two novel denitrifying alkalithermophilic bacteria, AT-1 and AT-2, were isolated
      from manure-amended soil. The isolates grew at 35-65 degrees C with an optimum
      temperature at 50-60 degrees C, and pH 6.5-10.0 with an optimum pH at 9.5. Both
      isolates were Gram-positive, facultative anaerobic, non-motile rod-shaped
      bacteria. A phylogenetic analysis based on 16S rRNA sequence data indicated that
      both AT-1 and AT-2 are members of the genus Anoxybacillus. DNA-DNA hybridization
      revealed moderate relatedness between AT-1 and AT-2 and one phylogenetically
      related strain, A. pushchinensis K1 (69.5 and 69.1%, respectively). Comparative
      analysis of morphology and biochemical characteristics of the two isolates also
      showed similarity to A. pushchinensis K1. Based on these results, we identified
      AT-1 and AT-2 as A. pushchinensis. To our knowledge, this is the first report of
      denitrifying bacterium isolated from alkalithermophilic Anoxybacillus spp.

PMID- 16612553
TI  - A membrane-bound nitrate reductase encoded by the narGHJI operon is responsible
      for anaerobic respiration in Halomonas maura.
AB  - The halophilic bacterium Halomonas maura is capable of anaerobic respiration on
      nitrates. By insertional mutagenesis with the minitransposon Tn-5 we obtained the
      mutant Tc62, which was incapable of anaerobic respiration on nitrates. An
      analysis of the regions adjacent to the transposon allowed us to characterize the
      membrane-bound anaerobic-respiratory nitrate reductase narGHJI gene cluster in H.
      maura. We identified consensus sequences for fumarate and nitrate reductase
      regulator (FNR)-like protein-binding sites in the promoter regions of the nar
      genes and consensus sequences corresponding to the NarL binding sites upstream of
      the nar genes. RT-PCR analysis showed that the narGHJI operon was expressed in
      response to anaerobic conditions when nitrate was available as electron acceptor.
      This membrane-bound nitrate reductase is the only enzyme responsible for
      anaerobic respiration on nitrate in H. maura. In this article we discuss the
      possible relationship between this enzyme and a dissimilatory nitrate-reduction
      to-ammonia process (DNRA) in H. maura and its role in the colonization of the
      rhizosphere.

PMID- 16612554
TI  - The medial branch of the lateral branch of the posterior ramus of the spinal
      nerve.
AB  - In the needle insertion of epidural anesthesia with the paramedian approach, the
      needle can pass through the longissimus muscle in the dorsum of the patients.
      When the needle touches a nerve in the muscles, the patients may experience pain
      in the back. Obviously, the needle should avoid the nerve tract. To provide
      better anesthetic service, analysis of the structure and where the concerned
      nerves lie in that region is inevitable. MATERIAL AND METHOD: We studied five
      cadavers in this study. Two cadavers were fixed with Thiel's method. With these
      cadavers, we studied the nerve running of the posterior rami of the spinal nerve
      from the nerve root to the distal portion. Three of them were used for the study
      of transparent specimen, with which we studied the course and size of the nerve
      inside the longissimus muscle. RESULTS: We observed there were three branches at
      the stem of the posterior rami of the spinal nerves between the body segment T3
      and L5, i.e. medial branch, medial branch of the lateral branch and lateral
      branch of the lateral branch. The medial branch of the lateral branch supplied to
      the longissimus muscle. With the transparent specimen, we found that there were
      different nerve layouts between the upper thoracic, lower thoracic, upper lumbar,
      and lower lumbar segments in the medial branch of the lateral branch in the
      longissimus muscle. In the lower thoracic and upper lumbar segments, the medial
      branch of the lateral branch of the upper lumbar segments produced layers nerve
      network in the longissimus muscle. L1 and L2 nerves were large in size in the
      muscle. CONCLUSION: In the upper lumbar segments the medial branch of the lateral
      branch of the posterior rami of the spinal nerve produced dense network in the
      longissimus muscle, where the epidural needle has high possibility to touch the
      nerve. Anesthetists have to consider the existence of the medial branch of the
      lateral branch of the posterior rami of the spinal nerve when they insert the
      needle in the paramedical approach to the spinal column.

PMID- 16612555
TI  - Microsurgical anatomy of intralaryngeal distribution of the inferior laryngeal
      nerve.
AB  - The functional results of a partial laryngeal surgery or a laryngeal
      reinnervation depend on the precise knowledge of the intra laryngeal anatomy of
      the inferior laryngeal nerve (ILN). Ten human larynges without known laryngeal
      disorders were obtained from human cadavers for ILN microdissection. Intra
      laryngeal ILN branching patterns were determined bilaterally. The lengths of the
      vertical, genu and oblique segments of the anterior division of ILN and the
      distance between the nerve within the paraglottic space and the cricothyroid
      articulation (CTA) were measured with a digital microcaliper. The mean lengths of
      the vertical, genu and oblique segments were 10.82, 5.89 and 9.29 mm,
      respectively. The mean distance between the nerve in the paraglottic space and
      the CTA was 11.20 mm. Key anatomical landmarks of the abductor division (vertical
      and genu segments of ILN) were the lateral border of posterior cricoarytenoid
      (PCA) muscle and the superior ligament of the CTA. The two-branch pattern for the
      lateral border of the PCA muscle has been the most frequent (50%). A branch of
      interarytenoid muscle (IA) originated from the genu segment. One or two branches
      for the PCA muscle has been identified in 75% of cases from the IA neural plexus
      on the front side of PCA muscle. The adductor division for the thyroarytenoid
      muscle and the lateral cricoarytenoid muscle was the oblique segment of the
      nerve. We conclude that abductor and adductor divisions of intra laryngeal ILN
      can be readily identified and the knowledge of key landmarks allows preservation
      of the ILN during partial surgery of the larynx and possibly selective muscle
      reinnervation.

PMID- 16612556
TI  - Differential activation of mitogen-activated protein kinases in ischemic and
      nitroglycerin-induced preconditioning.
AB  - Previous studies have shown that the cardioprotective effect of ischemic
      preconditioning (IPC) can be mimicked pharmacologically with clinically relevant
      agents, including nitric oxide (NO) donors. However, whether pharmacological
      preconditioning shares the same molecular mechanism with IPC is not fully
      elucidated. The present study aimed to determine the activation of mitogen
      activated protein kinases (MAPKs) (ERK1/2, p38 MAPK and p46/p54 JNKs) during
      ischemia and at reperfusion in nitroglycerin-induced preconditioning as compared
      to IPC and to correlate this with the conferred cardioprotection in anesthetized
      rabbits. Sixty minutes of intravenous administration of nitroglycerin was capable
      of inducing both early and late phase preconditioning in anesthetized rabbits, as
      it was expressed by the reduction of infarct size. Despite the cardioprotective
      effect conferred by both ischemic and nitroglycerin-induced preconditioning,
      there was a differential phosphorylation of MAPKs between the studied groups. p38
      MAPK was activated early in ischemia in both ischemic and the early nitroglycerin
      induced preconditioning while JNKs were markedly increased only after IPC.
      Furthermore, in these groups, ERK1/2 were activated during reperfusion. A
      different profile was observed in the late preconditioning induced by
      nitroglycerin with increased p38 MAPK and ERK1/2 phosphorylation during late
      ischemia. No activation of JNKs was observed at any time point in this group. It
      seems that activation of individual MAPK subfamilies depends on the nature of
      preconditioning stimulus.

PMID- 16612557
TI  - Paradoxical response to water immersion in replanted fingers.
AB  - When the fingers are immersed in water digital blood flow is reduced and the skin
      wrinkles, suggesting that vasoconstriction plays a role. However, is wrinkling
      due to sympathetic activation or some intrinsic property of the skin? To define
      the role of autonomic innervation in skin wrinkling we measured changes in blood
      perfusion (Laser Doppler Perfusion Imager) in 20 successfully replanted fingers
      (mean time after complete amputation 17.5 +/- 5.2 months). We compared responses
      in replanted fingers with those in corresponding contralateral normal fingers
      before and immediately after immersion in saline (0.5 mol/l NaCl at 40 degrees
      C). In the normal fingers, immersion caused a decrease in blood flow by 27.6 +/-
      11.5% and skin wrinkling. However, in the replanted fingers blood flow increased
      by 22.8 +/- 19.6% and the skin did not wrinkle. The paradoxical cutaneous
      vasodilatation and absence of wrinkling in the denervated fingers suggests that
      sympathetic innervation is important in water-immersion skin wrinkling.

PMID- 16612559
TI  - Zigzag instability of a chi disclination line in a cholesteric liquid crystal.
AB  - We studied the formation of chi disclination lines in planar cholesteric samples
      placed in a temperature gradient near the cholesteric to smectic A phase
      transition. We observed that the first simple line which forms close to the
      smectic-cholesteric front zigzags when it is perpendicular to the direction of
      planar anchoring and is straight for other orientations. This instability is
      similar to Herring instability for crystalline surfaces. We show numerically that
      it originates from a strong increase of the elastic anisotropy close to the
      transition. In addition, we propose a new method to measure the pitch divergence
      at the smectic to cholesteric phase transition.

PMID- 16612560
TI  - Faceting and stability of smectic A droplets on a solid substrate.
AB  - It is shown that a smectic A droplet deposited on a solid substrate treated for
      strong homeotropic anchoring is faceted at the top in spite of the fact that
      there are no steps at the free surface, but instead edge dislocations in the
      bulk. The radius of the facet and the full profile of the curved part of the
      droplet are determined as a function of the temperature in the vicinity of a
      nematic-smectic A phase transition. It is shown that the observed profiles do not
      correspond to the actual equilibrium shape, but to metastable configurations
      close to their point of marginal stability. In addition, we predict that the
      profiles must be different for a given temperature depending on whether the
      droplet has been heated or cooled down to reach this temperature. Finally, we
      discuss the problem of the formation of giant dislocations in big droplets
      (Grandjean terraces).

PMID- 16612561
TI  - Spinodal wrinkling in thin-film poly(ethylene oxide)/polystyrene bilayers.
AB  - Optical microscopy and atomic force microscopy were used to study a novel
      roughness-induced wrinkling instability in thin-film bilayers of poly(ethylene
      oxide) (PEO) and polystyrene (PS). The observed wrinkling morphology is
      manifested as a periodic undulation at the surface of the samples and occurs when
      the bilayers are heated above the melting temperature of the semi crystalline PEO
      (T(m) = 63 Celsius) layer. During the wrinkling of the glassy PS capping layers
      the system selects a characteristic wavelength that has the largest amplitude
      growth rate. This initial wavelength is shown to increase monotonically with
      increasing thickness of the PEO layer. We also show that for a given PEO film
      thickness, the wavelength can be varied independently by changing the thickness
      of the PS capping layers. A model based upon a simple linear stability analysis
      was developed to analyse the data collected for the PS and PEO film thickness
      dependences of the fastest growing wavelength in the system. The predictions of
      this theory are that the strain induced in the PS layer caused by changes in the
      area of the PEO/PS interface during the melting of the PEO are sufficient to
      drive the wrinkling instability. A consideration of the mechanical response of
      the PEO and PS layers to the deformations caused by wrinkling then allows us to
      use this simple theory to predict the fastest growing wavelength in the system.

PMID- 16612562
TI  - Psoriasin and its allergenic bovine homolog Bos d 3.

PMID- 16612563
TI  - Cancer and blood coagulation.
AB  - In human patients, blood coagulation disorders often associate with cancer, even
      in its early stages. Recently, in vitro and in vivo experimental models have
      shown that oncogene expression, or inactivation of tumour suppressor genes,
      upregulate genes that control blood coagulation. These studies suggest that
      activation of blood clotting, leading to peritumoral fibrin deposition, is
      instrumental in cancer development. Fibrin can indeed build up a provisional
      matrix, supporting the invasive growth of neoplastic tissues and blood vessels.
      Interference with blood coagulation can thus be considered as part of a
      multifaceted therapeutic approach to cancer.

PMID- 16612564
TI  - YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes
      and is related to insulin resistance.
AB  - OBJECTIVE AND DESIGN: YKL-40 participates in inflammatory states and vascular
      processes, which implies that comparison can be made with other inflammatory
      markers associated with insulin resistance and type 2 diabetes (T2D). In the
      present study levels of plasma YKL-40 and serum hsCRP were evaluated in patients
      with T2D. MATERIALS AND METHODS: Patients with T2D and age-matched healthy
      controls participated in the study. Insulin resistance was estimated using HOMA
      IR model. Biochemical parameters were measured in venous blood after a 10 h fast.
      RESULTS: Patients with T2D were insulin resistant (p<0.001) and had raised levels
      of plasma YKL-40 (p<0.001) and serum hsCRP (p<0.001). YKL-40 was correlated with
      HOMA-IR (r=0.23, p<0.01), NEFA (r=0.32, p<0.001) and triglycerides (r=0.24,
      p<0.05). YKL-40 and hsCRP were not correlated (r=0.17, p=NS). All participants
      with hsCRP<1 mg/l had higher insulin sensitivity (p<0.05 and p<0.01,
      respectively). HsCRP were predicted by HOMA-IR and BMI (r2=0.48, p<0.01). Plasma
      YKL-40 was predicted by HOMA-IR and triglycerides (r2=0.27, p<0.01). CONCLUSIONS:
      YKL-40 and hsCRP are elevated in patients with T2D and are related to insulin
      resistance. No correlation was found between YKL-40 and hsCRP indicating that
      increased levels of YKL-40 occur independently from elevated plasma hsCRP.

PMID- 16612565
TI  - Comparison of the pharmacology of hydroxamate- and carboxylate-based matrix
      metalloproteinase inhibitors (MMPIs) for the treatment of osteoarthritis.
AB  - OBJECTIVE AND DESIGN: Hydroxamic-and carboxylic-acid based matrix
      metalloproteinase inhibitors (MMPIs) were compared for their potency against
      various MMPs, pharmacodynamic properties and in vivo efficacy in a model of
      cartilage degeneration. MATERIALS AND METHODS: The MMPIs were evaluated for their
      ability to inhibit human MMPs using the quenched fluorescence assay. The ability
      of the MMPIs to inhibit the degeneration of the knee joint was evaluated in rats
      injected intraarticularly with iodoacetate. The amount of MMPI in the plasma and
      cartilage was determined using liquid chromatography/mass spectrometry/mass
      spectrometry (LC/ MS/MS). Plasma protein binding was measured by ultrafiltration
      and unbound MMPI was quantitated using HPLC. RESULTS: The hydroxamic acid based
      inhibitor PGE-3321996 and the carboxylic acids PGE-2909492 and PGE-6292544 were
      potent MMP-13 inhibitors, but only the hydroxamic acid PGE 3321996 demonstrated
      significant inhibition of knee degeneration in the rat iodoacetate model. Both of
      the carboxylic acids demonstrated superior pharmacokinetic properties and
      established much higher plasma concentrations than the hydroxamic acid. However,
      neither of the carboxylic acids was detectable in the cartilage, whereas, the
      hydroxamic acid was present in both the cartilage and the plasma. The carboxylic
      acid based MMPIs also demonstrated higher plasma protein binding (>99%) than the
      hydroxamic acid (79%). CONCLUSIONS: Carboxylic acid-based MMPIs were identified
      that had superior in vivo plasma exposure compared to a hydroxamic acid inhibitor
      but lacked in vivo efficacy in the rat iodoacetate model of cartilage
      degeneration. The lack of in vivo efficacy of the carboxylic acid based MMPIs
      were probably due to their lack of cartilage penetration which was related to
      their physicochemical properties.

PMID- 16612566
TI  - Release and permeation of histamine in isolated caecum epithelia of pigs.
AB  - OBJECTIVE: The objective was to investigate the role of histamine in the porcine
      caecum with special regard to its release and permeation. MATERIAL AND METHODS:
      Caecal epithelia were mounted in Ussing chambers. Mast cells were stimulated by
      A23187 (1 micromol/l). Permeation and changes in short-circuit current (Isc) were
      assessed after unilateral application of 3H-labelled histamine (100 micromol/l).
      Mucosal-to-serosal (ms) and serosal- to-mucosal (sm) flux rates were calculated
      based on the contralateral appearance of radioactive histamine label (hist-rad;
      representing histamine plus catabolites) as well as histamine. 14C-mannitol
      fluxes were measured to assess paracellular permeability. RESULTS: Both A23187
      and serosal addition of histamine increased Isc of caecal epithelia. The Isc
      increase due to A23187 was associated with an elevated histamine release from
      epithelia. A discrepancy between hist-rad and histamine fluxes (P<0.05) indicated
      efficient histamine catabolism (ca. 85%), which was decreased by blockage of
      diamine oxidase through aminoguanidine. Fluxes of histamine were correlated to
      14C-mannitol fluxes. Fluxes of hist-rad and histamine were higher in the sm
      direction. CONCLUSIONS: Histamine can be released from endogenous stores and acts
      on the epithelium. The absorption of luminal histamine is predominantly
      restricted by paracellular permeability and catabolism. The latter is only
      partially catalysed by diamine oxidase.

PMID- 16612567
TI  - Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of
      nitric oxide.
AB  - OBJECTIVE: Articular cartilage is an avascular tissue in which chondrocytes are
      exposed to hypoxic conditions. We previously demonstrated that reactive oxygen
      species (ROS) induced apoptosis of chondrocytes. We also demonstrated that nitric
      oxide (NO) was induced when chondrocytes were exposed to hypoxia and that NO
      inhibited the ROS-induced apoptosis. Hyaluronan (HA) is a high molecular weight
      glycosaminoglycan whose antioxidative effects have been reported. The purpose of
      the present study was to determine whether HA synthesis was induced in
      chondrocytes exposed to hypoxia, and, if so, whether the hypoxia-induced HA
      synthesis is regulated by NO. METHODS: Bovine articular chondrocytes were used in
      this study. Levels of HA were determined by the sandwich enzyme-binding assay.
      Expression of HA synthase (HAS) was determined with reverse transcription
      polymerase chain reaction. The production of NO was examined using the Griess
      reaction. We also determined inducible nitric oxide synthase (iNOS) enzyme
      synthesis using the histochemistry and Western blot analysis. RESULTS:
      Chondrocytes cultured under hypoxic conditions exhibited enhanced HA synthesis.
      When the NO inhibitors, L-NMMA and L-NAME, were added, the hypoxia-enhanced HA
      levels in the culture medium were significantly inhibited. CONCLUSIONS:
      Endogenous NO synthesis plays an important role in hypoxia-enhanced HA synthesis.

PMID- 16612568
TI  - Substance P stimulates release of RANKL via COX-2 expression in human dental pulp
      cells.
AB  - OBJECTIVE: Our previous study found that substance P (SP), a sensory
      neuropeptide, was expressed in the dental pulp of rats during experimental tooth
      movement. We examined the effects of SP on the production of prostaglandin (PG)
      E2 and the receptor activator of nuclear factor- B ligand (RANKL) by human dental
      pulp fi broblast-like (HDPF) cells. MATERIALS AND METHODS: SP was added to
      cultured HDPF cells at concentrations ranging from of 10(-4) to 10(-12) mol/L.
      PGE2 and soluble RANKL (sRANKL) levels were determined using enzyme-linked
      immunosorbent assay kits. Gene expression was confi rmed by RT-PCR analysis. Pit
      formation assays using dentin slices were carried out to examine the effect of SP
      on osteoclastogenesis. RESULTS: The levels of PGE2 and sRANKL increased in the
      presence of SP, though the increases were greater in the experimental groups in
      both a time- and concentration-dependent manner, and the increase of RANKL was
      partially mediated by PGE2. The gene expression of cyclooxygenase (COX)-2 and
      RANKL was up-regulated, and conditioned medium samples obtained from HDPF cells
      treated with SP induced bone resorption. CONCLUSIONS: SP stimulated the
      production of PGE2 and RANKL, and promoted bone resorption. Therefore, SP may be
      involved in pulpal inflammation and root resorption during orthodontic tooth
      movement.

PMID- 16612569
TI  - Is the United States an outlier in health care and health outcomes? A preliminary
      analysis.
AB  - U.S. health care is often seen as an outlier, with high costs and only middling
      outcomes. This view implies a household production function for health, with both
      health care and lifestyle serving as inputs. Building on earlier work by Miller
      and Frech (2004), we make this argument explicit by estimating a production
      function from augmented OECD data. This allows us to determine whether the U.S.
      is literally an outlier; which turns on whether the United States is very far off
      the production surface. We find that the Unites States is somewhat less
      productive than the average OECD country, but that a substantial part of the
      observed difference results from poor lifestyle choices, particularly obesity.

PMID- 16612570
TI  - Employer choices of family premium sharing.
AB  - In 1997, nearly two-thirds of married couples with children under age 18 were
      dual-earner couples. Such families may have a variety of insurance options
      available to them. If so, declining a high employee premium contribution may be a
      mechanism for one spouse to take money wages in lieu of coverage while the other
      spouse takes coverage rather than high wages. Employers may use these preferences
      and the size of premium contributions to encourage workers to obtain family
      coverage through their spouse. The purpose of this paper is to explore the
      effects of labor force composition, particularly the proportion of dual-earner
      couples in the labor market, on the marginal employee premium contribution
      (marginal EPC) for family coverage. We analyze data from the 1997-2001 Medical
      Expenditure Panel Survey--Insurance Component (MEPS-IC) List Sample of private
      establishments. We find strong evidence that the marginal EPC for family coverage
      is higher when there is a larger concentration of women in the workforce, but
      only in markets with a higher proportion of dual-earner households.

PMID- 16612571
TI  - OBRA 1987 and the quality of nursing home care.
AB  - Because minimum government standards for quality regulate only part of the market
      failure, they may have unintended effects. We present a general theory of how
      government regulation of quality of care may affect different market segments,
      and test the hypotheses for the nursing home market. OBRA 1987 was a sweeping
      government reform to improve the quality of nursing home care. We study how the
      effect of OBRA on the quality of nursing home care, measured by resident
      outcomes, varied with nursing home profitability. Using a semi-parametric method
      to control for the endogenous effects of regulation, we found that this landmark
      legislation had a negative effect on the quality of care in less profitable
      nursing homes, but improved the quality in more profitable nursing homes during
      the initial period after OBRA. But, this legislation had no statistically
      significant effect in the later period when the regulation was weakly enforced.

PMID- 16612572
TI  - Reimbursing for the costs of teaching and research in Finnish hospitals: a
      stochastic frontier analysis.
AB  - In this study stochastic frontier cost function was used to estimate the teaching
      and research costs of Finnish hospitals. Predicted efficiency adjusted costs were
      calculated and compared to evaluate the current level of teaching and research
      reimbursement. The efficiency adjustment had significant impact on the marginal
      and average cost estimates of the teaching and research output. The results
      suggest that the average rate of teaching and research reimbursement should be
      approximately 14.6% of the total operating costs in university teaching
      hospitals. The main finding was that the university teaching hospitals were
      underfunded with respect to both research and teaching output.

PMID- 16612573
TI  - Rejection of RG-2 gliomas is mediated by microglia and T lymphocytes.
AB  - Immunotherapy holds great promise for the treatment of invasive brain tumors, and
      we are interested specifically in evaluating immune stimulation of microglial
      cells as one potential strategy. In order to better understand the tumor fighting
      capabilities of microglial cells, we have compared the responses of syngeneic
      (Fisher 344) and allogeneic (Wistar) rat strains after intracranial implantation
      of RG-2 gliomas. Animals were evaluated by clinical examination, magnetic
      resonance imaging (MRI) and immunohistochemistry for microglial and other immune
      cell antigens. While lethal RG-2 gliomas developed in all of the Fisher 344 rats,
      tumors grew variably in the Wistar strain, sometimes reaching considerable sizes,
      but eventually all of them regressed. Tumor regression was associated with
      greater numbers of T cells and CD8 positive cells and increases in MHC I and CD4
      positive microglia. Our findings suggest that the combined mobilization of
      peripheral and CNS endogenous immune cells is required for eradicating large
      intracranial tumors.

PMID- 16612574
TI  - Inhibition of hypoxia inducible factor-1alpha (HIF-1alpha) decreases vascular
      endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas.
AB  - INTRODUCTION: Hypoxia inducible factor-1alpha (HIF-1alpha) regulates vascular
      endothelial growth factor (VEGF), the presumed principal mediator of angiogenesis
      in malignant gliomas, under normal physiologic conditions. We examined the effect
      of HIF-1alpha on VEGF secretion, tumor growth, and angiogenesis in malignant
      gliomas. METHODS: We examined 175 human gliomas for expression of HIF-1alpha and
      its downstream-regulated proteins. HIF-1alpha expression and VEGF secretion in
      glioma cell lines under normoxia and hypoxia were examined using ELISA and
      Western blot. Malignant glioma cell lines were transfected with dominant-negative
      HIF-1alpha (DN-HIF-1alpha) expression vector or siRNA constructs against the HIF
      1alpha gene. Growth studies were conducted on cells with the highest VEGF/HIF
      1alpha inhibition isolated from stable transfected cell lines. MIB-1-labeling
      index and microvascular density (MVD) measurements were performed on the in vivo
      tumors. RESULTS: HIF-1 expression correlates with malignant glioma phenotype and
      was not confined to perinecrotic, pseudopalisading cells. VEGF and HIF-1
      expression was high in glioma cell lines even under normoxia, and increased after
      exposure to hypoxia or growth factor stimulation. Cells transfected with DN-HIF
      1alpha or HIF-1alpha siRNA demonstrated decreased HIF-1alpha and VEGF secretion.
      In vivo but not in vitro growth decreased in response to VEGF and HIF-1
      inhibition. HIF-1 siRNA studies showed decreased VEGF secretion and in vitro and
      in vivo growth of glioma cell lines. MVD was unchanged but MIB-1 proliferation
      index decreased for both types of HIF-1 inhibition. CONCLUSIONS: VEGF and HIF
      1alpha are elevated in malignant gliomas. HIF-1alpha inhibition results in VEGF
      secretion inhibition. HIF-1alpha expression affects glioma tumor growth,
      suggesting clinical applications for malignant glioma treatment.

PMID- 16612575
TI  - Beneficial role of aminoguanidine on acute cardiomyopathy related to doxorubicin
      treatment.
AB  - Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has
      cardiotoxicity as a major side effect. One mechanism of this toxicity is believed
      to involve the reactive oxygen radical species (ROS); these agents likely account
      for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an
      effective antioxidant and free radical scavenger which has long been known to
      protect against ROS formation. We investigated the effects of AG on DOX-induced
      changes in thiobarbituric acid reactive substances (TBARS) and reduced
      glutathione (GSH) content. The rats were divided into four groups:1) Control; 2)
      DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose
      3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg
      AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg
      for 3 days. DOX administration to control rats increased TBARS and decreased GSH
      levels. AG administration before DOX injection caused significant decrease in
      TBARS and increase in GSH levels in the heart tissue when compared with DOX only.
      Morphological changes, including severe myocardial fibrosis and inflammatory cell
      infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX
      induced heart damage. Therefore AG could protect the heart tissue against free
      radical injury. The application of AG during cancer chemotherapy may attenuate
      tissue damage and improve the therapeutic index of DOX.

PMID- 16612576
TI  - Superior disembedding performance of high-functioning individuals with autism
      spectrum disorders and their parents: the need for subtle measures.
AB  - We assessed the disembedding performance on the Embedded Figures Test (EFT) of
      high-functioning subjects with autism or autism spectrum disorders from multi
      incidence families and the performance of their parents. The individuals with
      autism spectrum disorders were significantly faster than matched controls in
      locating the shape, but their parents were not faster than a control group of
      parents. However, both the individuals with autism spectrum disorders and their
      fathers made significantly fewer incorrect attempts before finding the right
      shape than matched controls. These results suggest that the number of incorrect
      attempts is a more subtle measure than accuracy or response time for assessing
      superior disembedding skills and therefore may be useful in the assessment of
      individuals with autism spectrum disorders.

PMID- 16612577
TI  - How do they do it? Insight on calendar skills from an Asperger's savant.

PMID- 16612578
TI  - Delayed postconditionig initiates additive mechanism necessary for survival of
      selectively vulnerable neurons after transient ischemia in rat brain.
AB  - 1. The aim of this study was to validate the role of postconditioning, used 2
      days after lethal ischemia, for protection of selectively vulnerable brain
      neurons against delayed neuronal death. 2. Eight, 10, or 15 min of transient
      forebrain ischemia in rat (four-vessel occlusion model) was used as initial
      lethal ischemia. Fluoro Jade B, the marker of neurodegeneration, and NeuN, a
      specific neuronal marker were used for visualization of changes 7 or 28 days
      after ischemia without and with delayed postconditioning. 3. Our results confirm
      that postconditioning if used at right time and with optimal intensity can
      prevent process of delayed neuronal death. At least three techniques, known as
      preconditioners, can be used as postconditioning: short ischemia, 3
      nitropropionic acid and norepinephrine. A cardinal role for the prevention of
      death in selectively vulnerable neurons comprises synthesis of proteins during
      the first 5 h after postconditioning. Ten minutes of ischemia alone is lethal for
      70% of pyramidal CA1 neurons in hippocampus. Injection of inhibitor of protein
      synthesis (Cycloheximide), if administered simultaneously with postconditioning,
      suppressed beneficial effect of postconditioning and resulted in 50% of CA1
      neurons succumbing to neurodegeneration. Although, when Cycloheximide was
      injected 5 h after postconditioning, this treatment resulted in survival of 90%
      of CA1 neurons. 4. Though postconditioning significantly protects hippocampal CA1
      neurons up to 10 min of ischemia, its efficacy at 15 min ischemia is exhausted.
      However, protective impact of postconditioning in less-sensitive neuronal
      populations (cortex and striatum) is very good after such a damaging insult like
      15 min ischemia. This statement also means that up to 15 min of ischemia,
      postconditioning does not induce cumulation of injuries produced by the first and
      the second stress.

PMID- 16612579
TI  - Phosphoproteomic analysis of neurotrophin receptor TrkB signaling pathways in
      mouse brain.
AB  - 1. The signaling pathways activated by trkB neurotrophin receptor have been
      studied in detail in cultured neurons, but little is known about the pathways
      activated by trkB in intact brain. TrkB is a tyrosine kinase and protein
      phosphorylation is a key regulatory process in the neuronal signal transduction
      pathways. 2. We have investigated trkB signaling in the transgenic mice
      overexpressing trkB in postnatal neurons (trkB.TK) using phosphoproteomics. 3. We
      found that several proteins are overphosphorylated on tyrosine residues in the
      brain of trkB.TK mice and identified some of these proteins. 4. We demonstrate
      that the well characterized signaling molecules mitogen-activated protein kinase
      (MAPK) and cyclic AMP responsive element binding protein (CREB) were
      phosphorylated at a higher level in the brain of trkB.TK mice when compared to
      the wild type littermates. Furthermore, we found that beta-actin was tyrosine
      phosphorylated in the brain of the transgenic mice. 5. Our results demonstrate
      that phosphoproteomics is a sensitive approach to investigate signaling pathways
      activated in mouse brain.

PMID- 16612580
TI  - Eyewitness lineups: is the appearance-change instruction a good idea?
AB  - The Department of Justice's Guide for lineups recommends warning eyewitnesses
      that the culprit's appearance might have changed since the time of the crime.
      This appearance-change instruction (ACI) has never been empirically tested. A
      video crime with four culprits was viewed by 289 participants who then attempted
      to identify the culprits from four 6-person arrays that either included or did
      not include the culprit. Participants either received the ACI or not and all were
      warned that the culprit might or might not be in the arrays. The culprits varied
      in how much their appearance changed from the video to their lineup arrays, but
      the ACI did not improve identification decisions for any of the lineups.
      Collapsed over the four culprits, the ACI increased false alarms and filler
      identifications but did not increase culprit identifications. The ACI reduced
      confidence and increased response latency. Two processes that could account for
      these results are discussed, namely a decision criterion shift and a general
      increase in ecphoric similarity.

PMID- 16612581
TI  - Physiological changes in venous hemodynamics associated with elective fasciotomy.
AB  - It has been postulated that lower extremity fasciotomy may disrupt the calf
      musculovenous pump and predisposes to development of chronic venous insufficiency
      (CVI). However, studies based on trauma patients who undergo emergent fasciotomy
      are confounded by the possibility of concomitant vascular and soft tissue injury
      and use historical controls. This is a prospective study that evaluates venous
      hemodynamics in young patients undergoing elective fasciotomy for chronic
      exertional compartment syndrome (CECS), eliminating the problems associated with
      retrospective study of trauma patients. CECS was diagnosed by history and, when
      indicated, measurement of compartment pressures. Prior to elective two- or four
      compartment fasciotomy, each patient underwent lower extremity air
      plethysmography (APG) and colorflow duplex ultrasonography. These studies were
      repeated a minimum of 6 weeks postoperatively. Fifteen patients who had
      fasciotomies for CECS were studied; two of these patients had bilateral
      fasciotomies for a total of 17 limbs. There were 13 male and two female patients
      (average age 31.2 years). APG and colorflow duplex were performed an average of
      12 weeks after fasciotomy. Outflow fraction, venous volume, and ejection volume
      showed no significant changes postoperatively. However, the venous filling index
      (VFI) increased (0.9 +/- 0.1 vs. 1.1 +/- 0.1 mL/sec; p < 0.05, paired t-test),
      the ejection fraction tended to decrease (59 +/- 4% vs. 52 +/- 2%; p < 0.08,
      paired t-test), and the residual volume fraction (RVF) increased (26 +/- 3% vs.
      36 +/- 5%; p < 0.05, paired t-test). There were no patients with evidence of deep
      venous reflux. Two extremities with preoperative greater saphenous vein (GSV)
      reflux did not worsen, and three extremities developed new GSV reflux following
      fasciotomy, although VFI remained normal in each extremity. Elective fasciotomy
      for CECS does not lead to significant venous reflux but likely does diminish calf
      muscle pump function and increases RVF moderately in young adult patients. With
      longer follow-up this diminished calf muscle pump function may increase the risk
      of CVI.

PMID- 16612582
TI  - Expression of P2X receptors on immune cells in the rat liver during postnatal
      development.
AB  - Single and double-labeling immunofluorescence and RT-PCR expression of P2X
      receptor proteins and mRNAs were used in a study of the liver of postnatal rats.
      OX62 and ED1 were used as markers for dendritic and macrophage (Kupffer) cells
      respectively. The results showed that the P2X6 receptor subunit was up-regulated
      by 15-fold on hepatic sinusoid cells during postnatal days P1 to P60.
      Subpopulations of Kupffer cells co-expressed P2X4 and P2X6 receptor subunits and
      dendritic cells co-expressed P2X4 and P2X7 receptor subunits. Lipopolysaccharide
      (endotoxin) injected into the peritoneal cavity led to increased expression of
      the P2X6 receptor on Kupffer cells, suggesting that the P2X6 receptor subunit may
      be up-regulated by endotoxin. This study presents the first evidence that P2X
      receptors are widely distributed in the rat liver immune system and that
      activation of Kupffer and dendritic cells in the rat liver might be regulated by
      extracellular ATP.

PMID- 16612583
TI  - Determination of thallium in biological samples.
AB  - Determination of thallium has become a major interest because of its high
      toxicity, especially as the monovalent cation. Thallium poisoning in the human
      body must be checked quickly by analysis of biological samples. This review
      highlights the development of highly sensitive detection techniques applied to
      the determination of thallium in biological samples, with or without
      pretreatment, based on the literature compiled in Analytical Abstracts from 1990.

PMID- 16612584
TI  - Proteins as micro viscosimeters: Brownian motion revisited.
AB  - Translational and rotational diffusion coefficients of proteins in solution
      strongly deviate from the Stokes-Einstein laws when the ambient viscosity is
      induced by macromolecular co-solutes rather than by a solvent of negligible size
      as was assumed by A. Einstein one century ago for deriving the laws of Brownian
      motion and diffusion. Rotational and translational motions experience different
      micro viscosities and both become a function of the size ratio of protein and
      macromolecular co-solute. Possible consequences upon fluorescence spectroscopy
      observations of diffusing proteins within living cells are discussed.

PMID- 16612585
TI  - A generalization of the van-der-Pol oscillator underlies active signal
      amplification in Drosophila hearing.
AB  - The antennal hearing organs of the fruit fly Drosophila melanogaster boost their
      sensitivity by an active mechanical process that, analogous to the cochlear
      amplifier of vertebrates, resides in the motility of mechanosensory cells. This
      process nonlinearly improves the sensitivity of hearing and occasionally gives
      rise to self-sustained oscillations in the absence of sound. Time series analysis
      of self-sustained oscillations now unveils that the underlying dynamical system
      is well described by a generalization of the van-der-Pol oscillator. From the
      dynamic equations, the underlying amplification dynamics can explicitly be
      derived. According to the model, oscillations emerge from a combination of
      negative damping, which reflects active amplification, and a nonlinear restoring
      force that dictates the amplitude of the oscillations. Hence, active
      amplification in fly hearing seems to rely on the negative damping mechanism
      initially proposed for the cochlear amplifier of vertebrates.

PMID- 16612586
TI  - PET/CT cardiology: an area whose boundaries are still out of sight.

PMID- 16612587
TI  - Impact of sympathetic innervation on recurrent life-threatening arrhythmias in
      the follow-up of patients with idiopathic ventricular fibrillation.
AB  - PURPOSE: Idiopathic ventricular fibrillation (IVF) is defined as VF in the
      absence of any identifiable structural or functional cardiac disease. The
      underlying pathophysiological mechanisms are unknown. This study was performed to
      investigate the potential impact of sympathetic dysfunction, assessed by (123)I
      meta-iodo-benzylguanidine scintigraphy ((123)I-MIBG SPECT), on the long-term
      prognosis of patients with IVF. METHODS: (123)I-MIBG SPECT was performed in 20
      patients (mean age 37+/-13 years) with IVF. Mean follow-up of patients after
      study entry was 7.2+/-1.5 years (range 4.9-10.5 years). Ten patients (five men,
      five women; mean age 43+/-12 years; p=NS versus study group) with medullary
      carcinoma of the thyroid gland served as an age-matched control group. RESULTS:
      Abnormal (123)I-MIBG uptake was observed in 13 patients (65%). During follow-up,
      18 episodes of VF/fast polymorphic ventricular tachycardias occurred in four IVF
      patients with abnormal (123)I-MIBG uptake whereas only two episodes of
      monomorphic ventricular tachycardia (and no VF) occurred in a single IVF patient
      with normal (123)I-MIBG uptake. CONCLUSION: Impairment of sympathetic innervation
      may indicate a higher risk of future recurrent episodes of life-threatening
      ventricular tachyarrhythmias in patients with IVF. Studies in larger cohorts are
      required to validate the significance of (123)I-MIBG SPECT during the long-term
      follow-up of these patients.

PMID- 16612588
TI  - How few cancer cells can be detected by positron emission tomography? A frequent
      question addressed by an in vitro study.
AB  - PURPOSE: Positron emission tomography (PET) has gained widespread use in cancer
      diagnosis and treatment, but how many malignant cells are required for a tumour
      to be detected by PET? METHODS: Three human cancer cell lines [glioblastoma and
      two subtypes of small cell lung cancer (SCLC)] in concentrations from 10(4) to
      10(7) were seeded on six-well plates or plastic tubes and treated with
      [(18)F]fluorodeoxy-glucose (FDG) in vitro. FDG retention was measured in a PET/CT
      scanner and in a calibrated well counter. The clinical situation was simulated
      using a cylinder phantom with a background concentration of FDG. RESULTS: The
      theoretical detection limit was found to be around 10(5) malignant cells. In a
      cylinder phantom the detection limit was increased by a factor of 10. The FDG
      retention by the glioblastoma cell line was significantly higher than the
      activity of the SCLC cell line. FDG retention measured by PET and a gamma counter
      was closely correlated to the number of cells and a linear relationship was
      found. DISCUSSION: The detection limit of PET is in the magnitude of 10(5) to
      10(6) malignant cells. The experimental set-up was robust and well suited as a
      platform for further investigations of factors influencing the detection limit of
      PET.

PMID- 16612589
TI  - Lower haemoglobin level and subsequent decline in kidney function in type 2
      diabetic adults without clinical albuminuria.
AB  - AIMS/HYPOTHESIS: Anaemia has been suggested to be an independent risk factor for
      subsequent progression of advanced diabetic nephropathy; however, the
      relationship between haemoglobin levels and progression of nephropathy in
      patients without clinical albuminuria is unknown. METHODS: We conducted this
      prospective hospital-based cohort study of 464 type 2 diabetic patients (149
      women and 315 men, 55+/-13 [mean+/-SD] years of age) with serum creatinine <177
      micromol/l (2.00 mg/dl) and urinary albumin : creatinine ratio <300 mg/g
      creatinine. GFR was estimated using the equation formulated by the Modification
      of Diet in Renal Disease Study group, refitted for Japanese individuals. Most
      patients had haemoglobin concentrations in the normal range (144+/-15 g/l), only
      modest renal impairment (GFR: 74.8+/-14.5 ml min(-1) 1.73 m(-2)), and normal
      urinary albumin levels (81.5/18.5% with normo-/microalbuminuria). The primary
      outcome measurement was the rate of change in GFR determined by regression
      analysis with GFR as a function of time. Patients were followed up for a mean
      observation period of 5.0+/-0.9 (range: 2.5 to 6.2) years. RESULTS: Univariate
      and multiple regression analyses yielded a significant association between the
      rate of change in GFR and baseline haemoglobin concentration. After adjusting for
      covariates, the rate of decline in GFR was significantly greater in patients in
      the lowest haemoglobin quartile (-3.27 ml min(-1) 1.73 m(-2) year(-1)) than in
      the third (-2.71 ml min(-1) 1.73 m(-2) year(-1), p = 0.024) and highest quartiles
      (-2.78 ml min(-1) 1.73 m(-2) year(-1), p = 0.046). CONCLUSIONS/INTERPRETATION:
      Lower haemoglobin concentrations in type 2 diabetic patients without clinical
      albuminuria may be a significant predictor of subsequent decline in GFR.

PMID- 16612590
TI  - A new model of insulin-deficient diabetes: male NOD mice with a single copy of
      Ins1 and no Ins2.
AB  - AIMS/HYPOTHESIS: We describe a novel model of insulin-deficient diabetes with a
      single copy of the gene encoding insulin 1 (Ins1) and no gene encoding insulin 2
      (Ins2). MATERIALS AND METHODS: We constructed five lines of mice: mice with two
      copies of Ins1 (NOD( Ins1+/+,Ins2-/-)), mice with a single copy of Ins1 (NOD(
      Ins1+/-,Ins2-/-)), mice with two copies of Ins2 (NOD( Ins1-/-,Ins2+/+)), mice
      with a single copy of Ins2 (NOD( Ins1-/-,Ins2+/-)) and NOD( Ins1+/-,Ins2-/-) mice
      with a transgene encoding B16:Ala proinsulin. RESULTS: By 10 weeks of age, all
      male NOD( Ins1+/-,Ins2-/-) mice were diabetic, whereas all female NOD( Ins1+/
      ,Ins2-/-) were not diabetic (p < 0.0001). In contrast, neither male nor female
      NOD( Ins1-/-,Ins2+/-) with a single copy of Ins2 (rather than single copy of
      Ins1) developed early diabetes and no mice with two copies of either gene
      developed early diabetes. Islets of the diabetic male NOD( Ins1+/-,Ins2-/-) at
      this early age had no lymphocyte infiltration. Instead there was heterogeneous
      (between islet cells) weak staining for insulin. Although only male NOD( Ins1+/
      ,Ins2-/-) mice developed diabetes, both male and female NOD( Ins1+/-,Ins2-/-)
      mice had markedly decreased insulin content. In NOD( Ins1+/+,Ins2-/-), there was
      also a significant decrease in insulin content, whereas NOD( Ins1-/-,Ins2+/+)
      mice, and even NOD( Ins1-/-,Ins2+/-) mice, were normal. Male NOD( Ins1+/-,Ins2-/
      ) mice were completely rescued from diabetes by introduction of a transgene
      encoding proinsulin. On i.p. insulin tolerance testing, male mice had insulin
      resistance compared with female mice. CONCLUSIONS/INTERPRETATION: These results
      suggest that Ins1 is a 'defective gene' relative to Ins2, and that the mouse
      lines created provide a novel model of sex-dimorphic insulin-deficient diabetes.

PMID- 16612591
TI  - Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 reduces food intake and
      weight gain but maintains energy expenditure in diet-induced obese mice.
AB  - AIMS/HYPOTHESIS: The 11beta-hydroxysteroid dehydrogenase type-1 inhibitor
      BVT.2733 lowers blood glucose and insulin in mutant mouse models of obesity and
      diabetes. Its effects on energy balance and body composition, and their
      contribution to improved glucose homeostasis have received little attention.
      MATERIALS AND METHODS: BVT.2733 (100 mg/kg, orally) was given twice daily to lean
      and diet-induced obese mice for 16 or 17 days. A group of obese mice was pair-fed
      to the amounts consumed by BVT.2733-treated mice. RESULTS: In both obese and lean
      mice, BVT.2733 reduced food intake and weight gain, but increased water intake.
      Pair-feeding caused almost as great a decrease in body weight as BVT.2733. Energy
      expenditure was 38+/-8% higher in the BVT.2733-treated obese mice than in the
      pair-fed mice. Terminal plasma corticosterone was raised, lean body weight
      reduced and percentage fat unchanged in the pair-fed mice (control, 47.8+/-2.6%;
      pair-fed, 47.1+/-1.9%), whereas BVT.2733 did not reduce lean mass, but did reduce
      percentage fat (40.9+/-2.0%). BVT.2733 but not pair-feeding reduced both the
      glucose tolerance AUC and the plasma insulin concentration 30 min after giving
      glucose. CONCLUSIONS/INTERPRETATION: BVT.2733 reduced food intake but prevented a
      concomitant reduction in lean body mass and energy expenditure. The latter
      effects may have contributed to improved glucose tolerance.

PMID- 16612592
TI  - Cardiac contractile dysfunction in Lep/Lep obesity is accompanied by NADPH
      oxidase activation, oxidative modification of sarco(endo)plasmic reticulum Ca2+
      ATPase and myosin heavy chain isozyme switch.
AB  - AIMS/HYPOTHESIS: Obesity is an independent risk factor for heart diseases but the
      underlying mechanism is not clear. This study examined cardiac contraction,
      oxidative stress, oxidative modification of sarco(endo)plasmic reticulum Ca2+
      ATPase (SERCA) and the myosin heavy chain (MHC) isoform switch in obese mice.
      METHODS: Mechanical properties were evaluated in ventricular myocytes from
      C57BL/6J lean and Lep/Lep obese mice (formerly known as ob/ob mice), including
      peak shortening (PS), time to 50 or 90% PS, time to 50 or 90% relengthening
      (TR50, TR90), maximal velocity of shortening/relengthening (+/-dL/dt),
      intracellular Ca2+ and its decay (tau). Oxidative stress, lipid peroxidation,
      protein damage and SERCA activity were assessed by glutathione/glutathione
      disulfide, malondialdehyde, protein carbonyl and 45Ca2+ uptake, respectively.
      NADPH oxidase was determined by immunoblotting. RESULTS: Myocytes from Lep/Lep
      mice displayed depressed PS and +/- dL/dt, prolonged TR50, TR90, elevated resting
      [Ca2+]i, prolonged tau, reduced contractile capacity at high stimulus frequencies
      and diminished responsiveness to extracellular Ca2+ compared with lean controls.
      Cardiac glutathione/glutathione disulfide was decreased whereas malondialdehyde,
      protein carbonyl, membrane p47(phox) and membrane gp91(phox) were increased in
      the Lep/Lep group. SERCA isoenzyme 2a was markedly modified by oxidation in
      Lep/Lep hearts and associated with decreased 45Ca2+ uptake. The MHC isozyme
      displayed a shift from the alpha to the beta isoform in Lep/Lep hearts. Short
      term incubation of angiotensin II with myocytes mimicked the mechanical defects,
      SERCA oxidation and 45Ca2+ uptake seen in Lep/Lep myocytes. Incubation of the
      NADPH oxidase inhibitor apocynin with Lep/Lep myocytes alleviated contractile
      defects without reversing SERCA oxidation or activity.
      CONCLUSIONS/INTERPRETATION: These data indicate that obesity-related cardiac
      defects may be related to NADPH oxidase activation, oxidative damage to SERCA and
      the MHC isozyme switch.

PMID- 16612593
TI  - Non-viral in vivo immune gene therapy of cancer: combined strategies for
      treatment of systemic disease.
AB  - Many patients with various types of cancers have already by the time of
      presentation, micrometastases in their tissues and are left after treatment in a
      minimal residual disease state [Am J Gastroenterol 95(12), 2000]. To prevent
      tumour recurrence these patients require a systemic based therapy, but current
      modalities are limited by toxicity or lack of efficacy. We have previously
      reported that immune reactivity to the primary tumour is an important regulator
      of micrometastases and determinant of prognosis. This suggests that recruitment
      of specific anti-tumour mechanisms within the primary tumour could be used
      advantageously for tumour control as either primary or neo-adjuvant treatments.
      Recently, we have focused on methods of stimulating immune eradication of solid
      tumours and minimal residual disease using gene therapy approaches. Gene therapy
      is now a realistic prospect and a number of delivery approaches have been
      explored, including the use of viral and non-viral vectors. Non-viral vectors
      have received significant attention since, in spite of their relative delivery
      inefficiency, they may be safer and have greater potential for delivery of larger
      genetic units. By in vivo electroporation of the primary tumour with plasmid
      expressing GM-CSF and B7-1, we aim to stimulate immune eradication of the treated
      tumour and associated metastases. In this symposium report, we describe an
      effective gene based approach for cancer immunotherapy by inducing cytokine and
      immune co-stimulatory molecule expression by the growing cells of the primary
      tumour using a plasmid electroporation gene delivery strategy. We discuss the
      potential for enhancement of this therapy by its application as a neoadjuvant to
      surgical excision and by its use in combination with suppressor T cell depletion.

PMID- 16612594
TI  - Co-expression of alpha(1,3)galactosyltransferase and Bacillus thuringiensis PIPLC
      enhances hyperacute rejection of tumor cells.
AB  - The use of alpha(1,3)galactosyltransferase (alphaGT) as a method of inducing
      hyperacute rejection of tumors has been gaining interest recently. However, the
      approach is based in part on the sensitivity of each tumor line to the effects of
      complement lysis. Tumors expressing complement resistance factors such as
      membrane cofactor (CD46), decay accelerating factor (CD55) and protectin (CD59)
      have been shown to be more resistant to complement mediated lysis. Anchored to
      the membrane by a glycosylphosphoinositol moiety (GPI-anchored), CD55 and CD59
      can be cleaved by Bacillus thuringiensis phosphatidylinositol-specific
      phospholipase C (PIPLC). Complement resistant A549 human lung carcinoma cells
      were engineered to express both the murine alphaGT gene and the B. thuringiensis
      PIPLC gene to alleviate complement resistance and enhance alphagal-mediated
      cancer killing. The PIPLC native signal sequence was replaced with the human
      epidermal growth factor signal sequence, EGFssPIPLC, to induce secretion from
      A549. Expression of EGFssPIPLC resulted in complete removal of CD55 and CD59
      while sparing the non-GPI-anchored CD46. Results demonstrated that A549 cells
      transduced with two recombinant retroviral vectors carrying the alphaGT and
      EGFssPIPLC genes expressed high levels of alphagal epitope and exhibited a 5-fold
      increase in sensitivity to anti-alphagal mediated complement lysis.

PMID- 16612595
TI  - Immuno-gene therapy of cancer with tumour-mRNA transfected dendritic cells.
AB  - We have developed immuno-gene therapy for malignant melanoma and prostate cancer.
      The therapy is based on monocyte-derived dendritic cells (DCs) that are
      transfected with autologous melanoma-mRNA or mRNA from three prostate cancer cell
      lines (DU-145, LN-CaP and PC-3). A broad spectrum of tumour-associated antigens
      will be included in both DC-vaccines. The use of autologous melanoma-mRNA
      moreover allows targeting of individual tumour antigens that are specific to each
      patient. Effective protocols have been established for mRNA-transfection by
      square wave electroporation and for the generation of clinical grade DCs. A full
      scale preclinical evaluation demonstrated in vitro T cell responses in 6/6
      advanced melanoma patients. The responses were specific to antigens encoded by
      the transfected tumour-mRNA. Recently, we have conducted two phase I/II trials,
      in advanced malignant melanoma and androgen-resistant prostate cancer. Successful
      vaccine preparations were obtained for all 41 patients elected. No serious
      adverse effects were observed. Specific T cell responses (T cell proliferation
      and/or IFNgamma ELISPOT) were demonstrated in 9/19 evaluable melanoma patients
      and in 12/19 prostate cancer patients. The response rates were higher for
      patients receiving intradermal vaccination, compared to intranodal injection.
      Thirteen prostate cancer patients developed a decrease in log-slope PSA. The PSA
      response was significantly related to the T cell response (P=0.002). We conclude
      that the DC-vaccine is feasible and safe, and that T cell responses are elicited
      in about 50% of patients.

PMID- 16612596
TI  - Tumor-derived CD4(+)CD25(+) regulatory T cell suppression of dendritic cell
      function involves TGF-beta and IL-10.
AB  - CD4(+)CD25(+) regulatory T cells have been characterized as a critical population
      of immunosuppressive cells. They play a crucial role in cancer progression by
      inhibiting the effector function of CD4(+) or CD8(+) T lymphocytes. However,
      whether regulatory T lymphocytes that expand during tumor progression can
      modulate dendritic cell function is unclear. To address this issue, we have
      evaluated the inhibitory potential of CD4(+)CD25(+) regulatory T cells from mice
      bearing a BCR-ABL(+) leukemia on bone marrow-derived dendritic cells. We present
      data demonstrating that CD4(+)CD25(+)FoxP3(+) regulatory T cells from tumor
      bearing animals impede dendritic cell function by down-regulating the activation
      of the transcription factor NF-kappaB. The expression of the co-stimulatory
      molecules CD80, CD86 and CD40, the production of TNF-alpha, IL-12, and
      CCL5/RANTES by the suppressed DC is strongly down-regulated. The suppression
      mechanism requires TGF-beta and IL-10 and is associated with induction of the
      Smad signaling pathway and activation of the STAT3 transcription factor.

PMID- 16612598
TI  - Targeted and shielded adenovectors for cancer therapy.
AB  - Conditionally replicative adenovirus (CRAd) vectors are novel vectors with
      utility as virotherapy agents for alternative cancer therapies. These vectors
      have already established a broad safety record in humans and overcome some of the
      limitations of non-replicative adenovirus (Ad) vectors. In addition, one
      potential problem with these vectors, attainment of tumor or tissue selectivity
      has widely been addressed. However, two confounding problems limiting efficacy of
      these drug candidates remains. The paucity of the native Ad receptor on tumor
      tissues, and host humoral response due to pre-existing titers of neutralizing
      antibodies against the vector itself in humans have been highlighted in the
      clinical context. The well-characterized CRAd, AdDelta24-RGD, is infectivity
      enhanced, thus overcoming the lack of coxsackievirus and adenovirus receptor
      (CAR), and this agent is already rapidly progressing towards clinical
      translation. However, the perceived host humoral response potentially will limit
      gains seen from the infectivity enhancement and therefore a strategy to blunt
      immunity against the vector is required. On the basis of this caveat a novel
      strategy, termed shielding, has been developed in which the genetic modification
      of a virion capsid protein would provide uniformly shielded Ad vectors. The
      identification of the pIX capsid protein as an ideal locale for genetic
      incorporation of shielding ligands to conceal the Ad vector from pre-existing
      neutralizing antibodies is a major progression in the development of shielded
      CRAds. Preliminary data utilizing an Ad vector with HSV-TK fused to the pIX
      protein indicates that a shield against neutralizing antibodies can be achieved.
      The utility of various proteins as shielding molecules is currently being
      addressed. The creation of AdDelta24S-RGD, an infectivity enhanced and shielded
      Ad vector will provide the next step in the development of clinically and
      commercially feasible CRAds that can be dosed multiple times for maximum
      effectiveness in the fight against cancers in humans.

PMID- 16612597
TI  - Effects of interferon gamma on native human acute myelogenous leukaemia cells.
AB  - T cell targeting immunotherapy is now considered a possible strategy in acute
      myelogenous leukaemia (AML), and IFNgamma release may then contribute to the
      antileukaemic effects. We investigated the effects of IFNgamma on native human
      AML cells. Normal T cells could be activated to release IFNgamma in the presence
      of AML cells. Furthermore, high levels of CD119 (IFNgamma receptor alpha chain)
      expression were observed for all 39 patients examined. Receptor expression was
      decreased after exposure to exogenous IFNgamma, and receptor ligation caused
      Stat1 phosphorylation but no phosphorylation of the alternative messengers
      Erk1/2. The effect of exogenous IFNgamma on AML blast proliferation was dependent
      on the local cytokine network and IFNgamma (1) inhibited proliferation in the
      presence of exogenous IL1beta, GM-CSF, G-CSF and SCF; (2) had divergent effects
      in the presence of IL3 and Flt3 (65 patients examined); (3) inhibited
      proliferation in the presence of endothelial cells but had divergent effects in
      the presence of fibroblasts, osteoblasts and normal stromal cells (65 patients
      examined). IFNgamma increased stress-induced (spontaneous) in vitro apoptosis as
      well as cytarabine-induced apoptosis only for a subset of patients. Furthermore,
      IFNgamma decreased the release of proangiogenic CXCL8 and increased the release
      of antiangiogenic CXCL9-11. We conclude that IFNgamma can be released in the
      presence of native human AML cells and affect AML cell proliferation, regulation
      of apoptosis and the balance between pro- and antiangiogenic chemokine release.

PMID- 16612600
TI  - A mechanistic study of immune system activation by fusion of antigens with the
      ligand-binding domain of CTLA4.
AB  - Fusion proteins consisting of the ligand-binding domain of CTLA4 covalently
      attached to an antigen (Ag) are potent immunogens. This fusion strategy
      effectively induces Ag-specific immunity both when introduced as a DNA-based
      vaccine and as a recombinant protein. CTLA4 is a ligand for B7 molecules
      expressed on the surface of antigen-presenting cells (APCs), and this interaction
      is critical for the fusion protein to stimulate Ag-specific immunity. We show
      that interaction of the fusion protein with either B7-1 or B7-2 is sufficient to
      stimulate immune activity, and that T cells are essential for the development of
      IgG responses. In addition, we demonstrate that human dendritic cells (DCs)
      pulsed with CTLA4-Ag fusion proteins can efficiently present Ag to T cells and
      induce an Ag-specific immune response in vitro. These studies provide further
      mechanistic understanding of the process by which CTLA4-Ag fusion proteins
      stimulate the immune system, and represent an efficient means of generating Ag
      specific T cells for immunotherapy.

PMID- 16612599
TI  - Dendritic cell-based multi-epitope immunotherapy of hormone-refractory prostate
      carcinoma.
AB  - BACKGROUND: Dendritic cell (DC)-based immunotherapy is a promising approach to
      augment tumor antigen-specific T cell responses in cancer patients. However,
      tumor escape with down-regulation or complete loss of target antigens may limit
      the susceptibility of tumor cells to the immune attack. Concomitant generation of
      T cell responses against several immunodominant antigens may circumvent this
      potential drawback. In this trial, we determined the immunostimulatory capacity
      of autologous DC pulsed with multiple T cell epitopes derived from four different
      prostate-specific antigens in patients with advanced hormone-refractory prostate
      cancer. PATIENTS AND METHODS: Autologous DC of HLA-A*0201(+) patients with
      hormone-refractory prostate cancer were loaded with antigenic peptides derived
      from prostate stem cell antigen (PSCA(14-22)), prostatic acid phosphatase
      (PAP(299-307)), prostate-specific membrane antigen (PSMA(4-12)), and prostate
      specific antigen (PSA(154-163)). DC were intradermally applied six times at
      biweekly intervals followed-in the case of an enhanced immune response-by monthly
      booster injections. Immune monitoring during the time of ongoing vaccinations (12
      59 weeks) included ex vivo ELISPOT measurements, MHC tetramer analysis and in
      vitro cytotoxicity assays. RESULTS: Of the initial six patients, three qualified
      for long-term multi-epitope DC vaccination. This regime was tolerated well by all
      three patients. The vaccination elicited significant cytotoxic T cell responses
      against all prostate-specific antigens tested. In addition, memory T cell
      responses against the control peptides derived from influenza matrix protein and
      tetanus toxoid were efficiently boosted. Clinically, the long-term DC vaccination
      was associated with an increase in PSA doubling time. CONCLUSIONS: DC-based multi
      epitope immunotherapy with repeated boosting in men with hormone-refractory
      prostate carcinoma is feasible and generates efficient cellular antitumor
      responses.

PMID- 16612602
TI  - [Magnetic resonance imaging of the hand in rheumatoid arthritis. New scientific
      insights and practical application].
AB  - Magnetic resonance imaging (MRI) is a sensitive diagnostic modality for the
      detection of inflammatory changes in peripheral joints. Nevertheless, the
      widespread clinical use of MRI in assessing patients with early rheumatoid
      arthritis is still hampered by the technical complexity and higher cost of MRI
      compared with conventional radiography. This overview summarizes the results of
      recent research and gives practical tips on how to perform MRI of the hands. The
      authors present an MR protocol for hand imaging, discuss the pros and cons of low
      field MR scanners, and outline pitfalls and artifacts. The MRI changes associated
      with rheumatoid arthritis such as synovitis, tenosynovitis, erosions, and bone
      marrow edema are described including their prognostic significance. The proven
      facts on the validation and grading of MR changes in rheumatoid arthritis are
      summarized. Finally, the role of MRI in the differential diagnosis of arthritis
      is critically discussed.

PMID- 16612603
TI  - [Arthroplasty of the rheumatoid hand. Pre- and postoperative imaging with special
      consideration of biomechanical and pathobiomechanical aspects and its
      radiological evaluation].
AB  - Radiology plays a key role when the indications for arthroplasties of the hand
      and finger joints are determined and for the postoperative follow-up. On the one
      hand, the degree of inflammatory changes in all affected compartments is to be
      evaluated and graded; on the other hand, conventional radiograms allow for a
      first assessment of possible joint instability and impaired biomechanics. Both
      aspects influence the choice of the proper surgical therapeutic strategy.
      Osteolysis, deformity, fracture, prosthesis loosening or failure, heterotopic
      ossification, and foreign body-associated formation of granulation tissue are
      complications which can be detected on follow-up radiographs early on.

PMID- 16612604
TI  - [Pre- and postoperative radioligical evaluation of knee joint endoprothesis.
      Orthopedist's view].
AB  - The implantation of a knee arthroplasty is still a demanding operation. There is
      still no "golden standard" available, although a lot of guidelines have been
      declared. Because of this fact this article should provide the radiologist with
      an overview of and some background knowledge for the radiological evaluation of
      knee arthroplasty.

PMID- 16612606
TI  - Kinetic modelling of phenol co-oxidation using horseradish peroxidase.
AB  - Phenol is an industrial pollutant and its removal from industrial wastewaters is
      of great importance. In order to design optimised phenol removal procedures by
      using horseradish peroxidase-based systems, there are some points that have to be
      dealt with. One of the most important issues is the need for reliable kinetics as
      this is one of the difficulties found during process scale-up. Although
      simplified kinetics can be used for limited ranges of operating conditions, they
      are not usually reliable for the description of varying process conditions. The
      present work describes the implementation of a kinetic model, based on a
      mechanism, for the co-oxidation of phenol and 4-aminoantipyrine (Am-NH2), which
      is used as a chromogen agent, with hydrogen peroxide as the oxidant. The model
      covers not only the variation of the concentrations of all the species involved,
      but also the effect of temperature in the reaction. The estimation of kinetic
      rate constants and activation energies for the various steps in the mechanism is
      performed with a single optimisation procedure, and all the experimental results
      are described using a unique set of parameters, which, thus, is valid over an
      extended range of operating conditions. The mechanism allowed the determination
      of a reliable kinetic model which is appropriate for the range of experimental
      conditions used. The computational model was also tested with an independent set
      of experiments with different conditions from the ones for which the parameters
      were estimated.

PMID- 16612607
TI  - Morphological assembly mechanisms in Neotropical bat assemblages and ensembles
      within a landscape.
AB  - Empirical studies on bat assemblages have shown that richness is not appreciably
      influenced by local processes such as ecological interactions. However, most of
      these studies have been done in large areas that include high heterogeneity, and
      they analyse all bat species within such areas, and thus they may be not
      reflecting local but supra-community conditions. We followed an ecomorphological
      approach to assess how bat assemblages of species from the families
      Phyllostomidae and Mormoopidae, and ensembles of frugivorous bats, are assembled
      in local habitats within a single landscape. We measured the volume of the space
      defined by wing morphology and quantified the average distance between species
      within such a volume. Then, we related these measures to local richness. Such
      relationships were contrasted against relationships with random assemblages to
      test for statistical differences. At the ensemble level of organization, we found
      that the frugivorous bat morphological assembly mechanism is different from
      random patterns, and it corresponds to the volume-increasing model. On the other
      hand, bat assembly mechanisms may be ubiquitous at the assemblage level, because
      groups of species coexisting in a local habitat and delimited only by phylogeny
      include more than one ecological group with no potential to interact. Assembling
      processes are crucial to an understanding of species diversity in local
      communities, and ecomorphological analyses are very promising tools that may help
      in their study.

PMID- 16612608
TI  - [Gastritis from a histological point of view].
AB  - Since the rediscovery of spiral-shaped gastric bacteria in 1983 by Warren and
      Marshal numerous detailed facts have enlarged our knowledge base for a better
      understanding of gastritis. The WHO classified Helicobacter as a class 1
      carcinogen. Helicobacter plays a role in many diseases of the upper GI tract
      (gastric and duodenal ulcer, MALT lymphoma, and gastric cancer). Knowledge of the
      interaction between bacterium and host led to an improvement of the diagnosis of
      gastritis. Unfortunately endoscopy, histology, and patient's symptoms do not
      correlate with each other. Therefore, gastritis is a purely histological
      diagnosis. A histological diagnosis always needs to be accompanied by an
      etiological cause of the inflammation. Only when this information is given a
      clinical consequence can be drawn from a histological diagnosis. In Germany the
      so-called ABCD scheme of gastritis is widely used (A: autoimmune gastritis, B:
      bacterial gastritis, C: chemical reactive gastritis, D: other forms of
      gastritis). At least two antrum and two corpus biopsies (matrix diagnostics) are
      necessary to reach representative tissue with an acceptable probability. If less
      than these four (minimal standard) biopsies are taken, the histological diagnosis
      will remain uncertain.

PMID- 16612609
TI  - Macrolide use identified as risk factor for macrolide-resistant Streptococcus
      pneumoniae in a 17-center case-control study.
AB  - The objective of the case-control study presented here was to examine the risk
      factors for macrolide-resistant Streptococcus pneumoniae. As part of a 44-center
      U.S. surveillance study, 1,817 unique isolates of S. pneumoniae were collected
      from November 2002 through April 2003. Seventy-five randomly selected macrolide
      resistant isolates (cases) were each matched with one susceptible control.
      Macrolide use in the 6 weeks prior to sample collection was reported for seven
      cases and one control. The final conditional logistic regression model identified
      two statistically significant variables: a history of alcohol abuse was
      protective, while macrolide use in the 6 weeks prior to sample collection was a
      significant risk factor for macrolide-resistant S. pneumoniae. Macrolide
      resistance was associated with use of any antibiotic during the prior 6 weeks,
      and was most strongly associated with previous macrolide use.

PMID- 16612610
TI  - Clavicular osteomyelitis: a rare complication after surgery for head and neck
      cancer.
AB  - Clavicular osteomyelitis (COM) is a rarely described disease entity, occurring
      especially after head and neck surgery. We herein report the ninth case according
      to the English language literature and describe the pertinent diagnostic and
      therapeutic measures to treat this complication. A 63-year-old Caucasian male
      underwent total laryngectomy and partial pharyngectomy for a post-radiotherapy
      recurrence of a T2 hypopharyngeal cancer. He presented multiple systemic
      (cardiovascular problems, previous pneumonectomy, malnutrition) and local
      regional (previous radiotherapy, neck dissection, tracheostomy) factors favoring
      postoperative complications. Sixteen days after surgery, he developed a painful
      swelling with overlying erythematous skin at the level of the medial portion of
      the left clavicle. A purulent discharge from the adjacent stomal dehiscence was
      also noted. COM, suspected on the base of patient's history and clavicular
      inspection, was confirmed by CT scan. Surgical debridement allowed for definitive
      diagnosis, ruling out any possible suspicion of stomal recurrence or secondary
      localization to the clavicle. Cultures from the debrided bone sequestra grew
      Streptococcus pyogenes Group A and allowed for proper targeting of antibiotic
      therapy, which was carried out for 4 weeks after surgery. Four years after
      surgery the patient is tumor-free and does not show any sequela related to the
      COM or its treatment. COM is a rarely encountered complication after major head
      and neck surgery. Nevertheless, prompt diagnosis and treatment are mandatory due
      to the potential life-threatening evolution of this condition.

PMID- 16612611
TI  - Audiovestibular evolution in a patient undergoing surgical resection of a
      temporal bone myxoma.
AB  - Primary myxoma in the head and neck region occurs mostly in the maxilla and
      mandible, and rarely in the temporal bone. A 32-year-old female patient with
      temporal bone myxoma manifested as acute vertigo, headache, and tinnitus on the
      right ear. Audiometry and auditory brainstem response revealed normal responses,
      bilaterally. Vestibular function test displayed spontaneous nystagmus beating
      toward the left side. Absent ice water caloric response was disclosed on the
      right ear, whereas vestibular evoked myogenic potential test showed normal
      responses, bilaterally. MRI scan demonstrated a well-enhanced mass at the
      anterior middle portion of the right temporal bone with intracranial extension.
      Tumor excision via craniotomy was performed, and the histopathological study
      confirmed as myxoma. One year after operation, follow-up audiovestibular function
      tests revealed normal responses, except for 23 dB conductive hearing loss on the
      right ear.

PMID- 16612612
TI  - Defective expression of Galpha12 in the testes of azoospermia patients and in the
      spermatozoa with low motility.
AB  - Antibody to the Galpha12-subunit of guanine nucleotide regulatory proteins was
      used to determine whether the Galpha12 is present in adult human spermatogenic
      cells and to determine its role in dyszoospermia. Immunoblots from testes and
      spermatozoa demonstrated the presence of Galpha12 in the samples.
      Immunohistochemical analyses of testes found that Galpha12 was expressed in the
      cytoplasm of Leydig cells and was expressed in spermatids from the elongating Sb
      phase to mature sperm. Indirect immunofluorescence of human spermatozoa revealed
      the presence of Galpha12 in the neck region and the midpiece of the sperm.
      Galpha12 in spermatids and spermatozoa partially co-localized with F-actin and
      alpha-tubulin. Immunohistochemical analyses of tissues from three patients with
      non-obstructive azoospermia showed abnormal expression of Galpha12 in more than
      45% of spermatids. Furthermore, Western blots and indirect immunofluorescence
      found defective expression of Galpha12 in low-motility spermatozoa with midpieces
      that were bent on themselves. Therefore, it suggests that Galpha12 plays a role
      in polarity and tail formation as spermatids mature. Furthermore, Galpha12 may be
      a candidate protein responsible for azoospermia caused by spermatogenic
      disturbance or midpiece deformities.

PMID- 16612613
TI  - Genome-wide meta-analysis for rheumatoid arthritis.
AB  - Meta-analysis is being increasingly used as a tool for integrating data from
      different studies of complex phenotypes, because the power of any one study to
      identify causal loci is limited. We applied a novel meta-analytical approach
      (Loesgen et al. in Genet Epidemiol 21(Suppl 1):S142-S147, 2001) in compiling
      results from four studies of rheumatoid arthritis in Caucasians including two
      studies from NARAC (Jawaheer et al. in Am J Hum Genet 68:927-936, 2001; Jawaheer
      et al. in Arthritis Rheum 48:906-916, 2003), one study from the UK (MacKay et al.
      in Arthritis Rheum 46:632-639, 2001) and one from France (Cornelis et al. in Proc
      Natl Acad Sci USA 95:10746-10750, 1998). For each study, we obtained NPL scores
      by performing interval mapping (2 cM intervals) using GeneHunter2 (Kruglyak et
      al. in Am J Hum Genet 58:1347-1363, 1996; Markianos et al. in Am J Hum Genet
      68:963-977, 2001). The marker maps differed among the three consortium groups,
      therefore, the marker maps were aligned after the interval mapping was completed
      and the NPL scores that were within 1 cM of each other were combined using the
      method of Loesgen et al. (Genet Epidemiol 21(Suppl 1):S142-S147, 2001) by
      calculating the weighted average of the NPL score. This approach avoids some
      problems in analysis encountered by using GeneHunter2 when some markers in the
      sample are not genotyped. This procedure provided marginal evidence (P<0.05) of
      linkage on chromosome 1, 2, 5 and 18, strong evidence (P<0.01) on chromosomes 8
      and 16, and overwhelming evidence in the HLA region of chromosome 6.

PMID- 16612614
TI  - A novel locus (RP33) for autosomal dominant retinitis pigmentosa mapping to
      chromosomal region 2cen-q12.1.
AB  - Retinitis pigmentosa (RP) is a heterogeneous group of progressive degenerative
      disorders of the retina with a strong genetic component. Here, we report the
      clinical and genetic findings in a Chinese family in which autosomal dominant RP
      (adRP) was inherited by 13 affected members in four generations. Using a genome
      wide linkage screening approach, a novel disease locus (RP33) was assigned to the
      long arm of chromosome 2. A maximum multi-point LOD score of 4.69 was reached at
      marker D2S2222 in 2q11.2. Meiotic recombination events in affected members placed
      RP33 in a 15.5 cM region between D2S329 and D2S2229. From meiotic recombinations
      in two unaffected members RP33 was further refined to a 4.8 cM (9.5 Mb) interval
      flanked by D2S2159 and D2S1343 in chromosomal region 2cen-q12.1. No disease
      associated mutations were detected in the candidate genes SEMA4C, CNGA3 or HNK1ST
      from within the region. MERTK, a known disease gene for autosomal recessive RP
      located close to RP33 was similarly excluded. Clinically, the family presented
      relatively late onset of night blindness, gradually decreased visual acuity,
      progressive loss of peripheral visual field and typical RP fundus changes in the
      mid-periphery of the retina. In conclusion, a novel locus for adRP has been
      assigned to chromosomal region 2cen-q12.1, which in the present kindred was
      associated with a relatively late onset form of the disease.

PMID- 16612616
TI  - An mGluR2/3 antagonist, MGS0039, exerts antidepressant and anxiolytic effects in
      behavioral models in rats.
AB  - RATIONALE: Abnormalities of glutamatergic neurotransmission have been reportedly
      observed in psychiatric disorders. Previously, we demonstrated that (1R, 2R, 3R,
      5R, 6R)-2-Amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6
      dicarboxylic acid (MGS0039) is a selective antagonist for group II metabotropic
      glutamate receptors (mGluR2/3), and that it exerted antidepressant effects in
      some animal behavioral tests. OBJECTIVES: In the present study, we provide
      additional evidence that MGS0039 exhibits antidepressant and anxiolytic effects
      in experimental rodent models, which are predictive of clinical efficacy.
      METHODS: The learned helplessness (LH) paradigm, which is a common model used to
      examine the depressive state, was used to assess antidepressant effects of
      MGS0039. Moreover, anxiolytic effects of MGS0039 were investigated in the
      conditioned fear stress (CFS) model, which represents emotional abnormality,
      including anxiety. RESULTS: Intraperitoneal administration of MGS0039 (10 mg/kg)
      to rats for 7 days elicited a significant reduction in escape failures in the LH
      paradigm. In addition, rats treated with MGS0039 (2 mg/kg) showed significantly
      attenuated freezing behavior in a CFS model, indicating the anxiolytic-like
      potential of MGS0039. CONCLUSIONS: These results suggest that the blockade of
      mGluR2/3 with MGS0039 may be effective in the treatment of depressive and anxiety
      disorders.

PMID- 16612618
TI  - Salvage of the tibial malunion and nonunion with the use of angled blade plate:
      other treatment method.

PMID- 16612617
TI  - Persistent dysfunctional frontal lobe activation in former smokers.
AB  - OBJECTIVE: Chronic smoking and nicotine exposure are accompanied by impaired
      cognitive task performance, modulated cerebral activity in brain imaging studies,
      and neuritic damage in experimental animals. The profile of the described
      dysfunctions matches frontal lobe circuits which also play a role in reward
      processing and reinforcement behavior. However, it is largely unknown if cerebral
      dysfunctions are reversible or persist during long term abstinence. MATERIALS AND
      METHODS: Cortical activation during auditory target processing (oddball task,
      P300 component) was recorded with 32-channel EEG in 247 healthy subjects
      consisting of 84 smokers, 53 former smokers (mean time of abstinence 11.9 years),
      and 110 never smokers. RESULTS: Both current smokers and former smokers exhibited
      significantly diminished P300 amplitudes (Cz, Pz) relative to never smokers.
      Neuroelectric source analysis (low resolution brain electromagnetic tomography)
      revealed a hypoactivation of the anterior cingulate, orbitofrontal, and
      prefrontal cortex in smokers compared to never smokers. A similar profile of
      hypoactivation was observed in former smokers. CONCLUSION: For the first time,
      evidence is provided that dysfunctional activation of frontal lobe networks in
      smokers is also present in long term abstainers.

PMID- 16612619
TI  - Inferior stability of a biodegradable cement plug. 122 total hip replacements
      randomized to degradable or non-degradable cement restrictor.
AB  - INTRODUCTION: Modern cementing technique demands high intramedullar cement
      pressure to create an optimum fixed cement support of the femoral stem. Pressure
      resistant, stable closure of the canal therefore is absolutely necessary.
      Biodegradable cement restrictors, if corresponding to above mentioned attributes,
      could be of immense advantage in case of potential revision surgery. MATERIAL AND
      METHODS: A prospective, randomized trial was performed on a consecutive series of
      130 patients who underwent primary cemented total hip arthroplasty due to hip
      arthrosis to compare a degradable cement restrictor and a non-degradable cement
      restrictor in their ability to resist distal migration during stem insertion.
      RESULTS: The median cement plug length measured 27 mm (range -12 to 126 mm, 95%
      confidence interval (CI) 20-33 mm) in the biodegradable restrictor group and 15
      mm (range 0-61 mm, 95% CI 12-18 mm) in the non-degradable restrictor group
      (P=0.003). A significant effect of the relationship between the difference of
      restrictor size and the diameter of the femoral canal on length of cement distal
      of the tip of the stem in between the two groups was evident (P=0.031).
      CONCLUSION: The results indicate insufficient intramedullary plug fixation of the
      degradable restrictor probably due to the elastic material properties which also
      may lead to inferior precision in restrictor size choice.

PMID- 16612620
TI  - A transepiphyseal fracture of the proximal femur combined with a fracture of the
      mid-shaft of ipsilateral femur in a child: a case report and literature review.
AB  - The paper describes a rare fracture of proximal femur, classified by Delbet (Am J
      Surg 6:793-797, 1929) as type I (transepiphyseal type) combined with a fracture
      of the midshaft of ipsilateral femur in a 2-year-old child. Immediate operation
      with open reduction and internal fixation was successful. During the
      postoperative course, avascular necrosis (AVN) of capital femoral epiphysis was
      seen by bone scan. Applying an abduction orthosis used for the treatment of Legg
      Calve-Perthes disease, collapse of capital epiphysis was prevented. Although, a
      minimal area of AVN and coxa vara remained, no clinical complaints were recorded
      at the midterm follow-up. While reviewing the relevant literature, the type-I
      fractures need to be subclassified into two types for appropriate treatment
      and/or prediction of outcomes based on their anatomic location of the separated
      femoral capital epiphysis. In type Ia, femoral capital epiphysis is minimally
      displaced and within the acetabulum and in type Ib it is widely displaced and
      lying outside the capsule. Our case is a first case of a type Ib fracture of the
      proximal femur combined with a fracture of the midshaft of ipsilateral femur.
      Since the complication rate and the prognosis differed between two subclasses,
      type-Ib fractures need immediate surgical intervention, our case was prevented
      from massive AVN. And to prevent the collapse of femoral head following AVN, a
      major complication of the fracture of proximal femur in child, abduction orthosis
      is recommended as a choice of treatment.

PMID- 16612615
TI  - Treatment of human disease by adeno-associated viral gene transfer.
AB  - During the past decade, in vivo administration of viral gene transfer vectors for
      treatment of numerous human diseases has been brought from bench to bedside in
      the form of clinical trials, mostly aimed at establishing the safety of the
      protocol. In preclinical studies in animal models of human disease, adeno
      associated viral (AAV) vectors have emerged as a favored gene transfer system for
      this approach. These vectors are derived from a replication-deficient, non
      pathogenic parvovirus with a single-stranded DNA genome. Efficient gene transfer
      to numerous target cells and tissues has been described. AAV is particularly
      efficient in transduction of non-dividing cells, and the vector genome persists
      predominantly in episomal forms. Substantial correction, and in some instances
      complete cure, of genetic disease has been obtained in animal models of
      hemophilia, lysosomal storage disorders, retinal diseases, disorders of the
      central nervous system, and other diseases. Therapeutic expression often lasted
      for months to years. Treatments of genetic disorders, cancer, and other acquired
      diseases are summarized in this review. Vector development, results in animals,
      early clinical experience, as well as potential hurdles and challenges are
      discussed.

PMID- 16612621
TI  - Myocardial sleeves of pulmonary veins and atrial fibrillation: a postmortem
      histopathological study of 100 subjects.
AB  - Atrial fibrillation (AF) is triggered by ectopic beats originating from
      extensions of the left atrial myocardium over the pulmonary veins (PVs), so
      called myocardial sleeves. A total of 100 hearts (393 PVs) obtained at autopsy
      were studied. Of these, 50 were from patients with chronic AF and 50 from
      controls in sinus rhythm. Out of a total of 393 PVs studied, a sleeve was present
      in 349 PVs (88.8%). The myocardial sleeves frequently harboured senile atrial
      amyloid and scarring. These two changes were evaluated semi-quantitatively (grade
      0-3). Amyloidosis was found in 68% of all hearts and in 55% of all sleeves. It
      was more frequent in patients with AF (58.5%) than in those without (51.7%),
      however, without statistical significance (p values 0.948, 0.306, 0.166 and 1).
      Scarring was present in all 349 sleeves studied. It was significantly more severe
      in patients with AF (average grade 2.44) than in those without (average grade
      2.00) (p values <0.001, <0.1, <0.05 and <0.01). In conclusion, amyloidosis and
      particularly scarring of the myocardial sleeves of the pulmonary veins, appear to
      be common in the elderly population as an arrhythmogenic substrate for AF.

PMID- 16612622
TI  - Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma.
AB  - Endoglin (CD105) is a proliferation-associated protein abundantly expressed in
      angiogenic endothelial cells. Recent studies revealed that CD105 is intensively
      expressed in tumor vasculature, whereas intratumoral microvessel density (MVD)
      determined with the use of antibodies to CD105 has been found to be an important
      prognostic indicator for the outcome in a number of malignancies. In the current
      study, we investigated endoglin expression and evaluated MVD in 108 patients with
      head and neck squamous cell carcinoma. Endoglin was intensively expressed in
      intratumoral blood vessels, whilst lymphatics were rarely positive for CD105.
      High microvessel density was associated with a more aggressive tumor phenotype,
      including advanced clinical stage (p = 0.008) and the presence of lymph node
      metastasis at the time of diagnosis (p = 0.02). When microvessel counts were
      assessed for their prognostic values (high vs low MVD), there was a statistically
      significant difference in the overall survival among patients with tumors of the
      oral cavity and larynx (p < 0.001) and in the disease-free survival among
      patients with tumors of the lower lip (p = 0.01). The prognostic impact of
      microvessel density was not dependent on clinical stage or lymph node status. The
      results of the current study suggest that CD105 is a promising target for tumor
      imaging and prognosis.

PMID- 16612623
TI  - Genetic similarities and differences between lobular in situ neoplasia (LN) and
      invasive lobular carcinoma of the breast.
AB  - One of the most controversial issues in breast pathology is whether lobular
      neoplasia (LN) is a risk factor or a precursor lesion of invasive lobular
      carcinoma (ILC). This is consequent to the fact that no conclusive data on the
      biology of LN exist. Molecular studies of LN and ILC are scanty, variable, and
      not consistent. Clonality of 12 cases of LN and ILC present simultaneously in the
      same block has been studied. Cells from both lesions were obtained by
      microdissection and were studied for mitochondrial DNA (mtDNA), D-loop
      sequencing, and neighbor-joining trees. Eight of the same cases were studied with
      comparative genomic hybridization (CGH) array to have additional data consistent
      with mtDNA. In all cases, loss of heterozygosity was studied for D16S496,locus
      16q22.1 related to e-cadherin. It appears that no fewer than eight cases were
      genetically very similar (clonal) with mtDNA. Seven of these cases appeared also
      clonal with CGH array. It is concluded that in the present series, LN and ILC are
      genetically related lesions in the majority of cases and that LN might be the
      precursor of ILC.

PMID- 16612624
TI  - Comparative study of T84 and T84SF human colon carcinoma cells: in vitro and in
      vivo ultrastructural and functional characterization of cell culture and
      metastasis.
AB  - To better understand the relationship between tumor heterogeneity,
      differentiation, and metastasis, suitable experimental models permitting in vitro
      and in vivo studies are necessary. A new variant cell line (T84SF) exhibiting an
      altered phenotype was recently selected from a colon cancer cell line (T84) by
      repetitive plating on TNF-alpha treated human endothelial cells and subsequent
      selection for adherent cells. The matched pair of cell lines provides a useful
      system to investigate the extravasation step of the metastatic cascade. Since
      analysis of morphological differences can be instructive to the understanding of
      metastatic potential of tumor cells, we compared the ultrastructural and
      functional phenotype of T84 and T84SF cells in vitro and in vivo. The reported
      ultrastructural features evidence differences between the two cell lines;
      selected cells showed a marked pleomorphism of cell size and nuclei, shape, and
      greater surface complexity. These morphological differences were also coupled
      with biochemical data showing a distinct tyrosine phosphorylation-based
      signaling, an altered localization of beta-catenin, MAPK, and AKT activation, as
      well as an increased expression in T84SF cells of Bcl-X(L), a major regulator of
      apoptosis. Therefore, these cell lines represent a step forward in the
      development of appropriate models in vitro and in vivo to investigate colon
      cancer progression.

PMID- 16612625
TI  - Atherosclerosis research from past to present--on the track of two pathologists
      with opposing views, Carl von Rokitansky and Rudolf Virchow.
AB  - It is now clear that inflammation plays a key role in atherogenesis. As a matter
      of fact, signs of inflammation of atherosclerotic plaques have been observed for
      centuries and also constituted the basis for a fierce controversy in the 19th
      century between the prominent Austrian pathologist Carl von Rokitansky and his
      German counterpart, Rudolf Virchow. While the former attributed a secondary role
      to these inflammatory arterial changes, Virchow considered them to be of primary
      importance. We had the unique opportunity to address this controversy by
      investigating atherosclerotic specimens from autopsies performed by Carl von
      Rokitansky up to 178 years ago. Twelve atherosclerotic arteries originally
      collected between the years 1827 to 1885 were selected from the Collection
      Rokitansky of the Federal Museum of Pathological Anatomy, Vienna Medical
      University. Using modern sophisticated immunohistochemical and immunofluorescence
      techniques, it was shown that various cellular intralesional components, as well
      as extracellular matrix proteins, were preserved in the historic atherosclerotic
      specimens. Most importantly, CD3 positive cells were abundant in early lesions,
      thus, rather supporting Virchows's view, that inflammation is an initiating
      factor in atherogenesis. Furthermore, we hope to have opened a new and intriguing
      possibility to study various pathological conditions using valuable historical
      specimens.

PMID- 16612626
TI  - Effects of dibucaine on the endocytic/exocytic pathways in Trypanosoma cruzi.
AB  - Although local anesthetics (LA) are considered primarily Na+-channel blockers in
      the past decade, an alternative action of LA as inhibitors of fusion among
      compartments of the endocytic/exocytic pathways was described. In epimastigote
      forms of Trypanosoma cruzi, we observed that 50 mM dibucaine reduced the rates of
      uptake of bovine serum albumin (BSA) and immunoglobulin to 60% of control values
      in addition to the delay of exocytosis of cysteine proteases. Fusion among
      endocytic compartments was not inhibited in the presence of dibucaine because
      previously labeled reservosomes was loaded with a second label in sequential
      pulse-chase experiments. However, dibucaine reduced the degradation of BSA-gold
      complex in the reservosomes, which was not caused either by an inhibition of the
      whole proteolytic activity of the parasite or by a reduction on the expression
      levels of cruzipain. The immunocytochemical analysis suggested that the
      inhibition of the degradation of gold-labeled BSA in reservosomes could be due to
      a subversion of the regular traffic of proteases toward the reservosomes in
      dibucaine-treated cells.

PMID- 16612627
TI  - Experimental study of the effects of probiotics on Cryptosporidium parvum
      infection in neonatal rats.
AB  - To date, there is no efficient treatment for cryptosporidiosis and parasite
      eradication relies on innate and acquired immunity. In this study, we
      investigated the effect of administration of probiotic bacteria on the
      development and progression of the experimental infection in suckling rats. Rats
      were fed daily with 2.10(7) CFU of Lactobacillus casei-containing mixture,
      starting 2 days before the infection until the spontaneous clearance of the
      parasite. Effects on weight gain, parasite burden, mucosal histology and
      production of mucosal cytokines (IFNgamma, IL10 and TNFalpha) were studied.
      Although a trend to a more rapid clearance of parasites was noted in rats treated
      with probiotics, no significant effect of probiotics administration was observed
      in terms of weight gain, parasite burden, mucosal damage, or kinetics of mucosal
      cytokines during the course of infection. Overall, our results showed that the
      daily administration of L. casei-containing mixtures was unable to eradicate the
      parasite in our model.

PMID- 16612628
TI  - Analysing the effect of candidate genes on complex traits: an application in
      multiple sclerosis.
AB  - The conventional approach of candidate gene studies in complex diseases is to
      look at the effect of one gene at a time. However, as the outcome of chronic
      diseases is influenced by a large number of alleles, simultaneous analysis is
      needed. We demonstrate the application of multivariate regression and cluster
      analysis to a multiple sclerosis (MS) dataset with genotypes for 489 patients at
      11 candidate genes selected on their involvement in the immune response. Using
      multivariate regression, we observed that different sets of genes were associated
      with different disease characteristics that reflect different aspects of disease.
      Out of 15 polymorphisms, we identified one that contributed to the severity of
      disease. In addition, the set of 15 polymorphisms was predictive for yearly
      increase in lesion volume as seen on T1-weighted MRI (p=0.044). From this set, no
      individual polymorphisms could be identified after adjustment for multiple
      hypotheses testing. By means of a cluster analysis, we aimed to identify
      subgroups of patients with different pathogenic subtypes of MS on the basis of
      their genetic profile. We constructed genetic profiles from the genotypes at the
      11 candidate genes. The approach proved to be feasible. We observed three
      clusters in the sample of patients. In this study, we observed no significant
      differences in the usual clinical and MRI outcome measures between the different
      clusters. However, a number of consistent trends indicated that this clustering
      might be related to the course of disease. With a larger number of genes
      regulating the course of disease, we may be able to identify clinically relevant
      clusters. The analyses are easily implemented and will be applicable to candidate
      gene studies of complex traits in general.

PMID- 16612629
TI  - Phe-met-arg-phe (FMRF)-amide is a substrate source of NO synthase in the
      gastropod nervous system.
AB  - The possible involvement of the L-arginine-containing Phe-met-arg-phe (FMRF)
      amide (FMRFa) in neuronal nitric oxide (NO) biosynthesis was studied in a
      gastropod species. We found NADPH-diaphorase-positive neurons and FMRFa
      containing fibers in close proximity in the enteric nervous system.
      Administration of L-arginine and FMRFa induced quantitatively similar nitrite
      production in both intact intestinal tissues and tissue homogenates. These
      changes could be prevented by the presence of NOARG (an NO synthase inhibitor).
      Neither chemically modified FMRFa (D-arginine instead of L-arginine) nor amino
      acid constituents of FMRFa (methionine, phenylalanine) affected basal nitrite
      production. FMRFa-induced alterations were reduced in the presence of Na+ channel
      blockers (tetrodotoxin, amiloride, lidocaine), the Na+/K+ATPase inhibitor
      ouabain, or protease inhibitors (leupeptine, pepstatine-a). FMRFa and its amino
      acid constituents were analyzed by paper chromatography. When FMRFa was added to
      tissue homogenates, the peptide was eliminated within 1-2 min, whereas
      methionine, phenylalanine, arginine, and citrulline levels were elevated
      simultaneously. We tested the effects of FMRFa, L-arginine, and NOARG on
      intestinal contractile activity. FMRFa relaxed the intestine for 1-2 min and then
      induced contractions for 20-40 min. In the presence of NOARG, no relaxant effect
      of FMRFa was recorded. As administration of L-arginine strongly inhibits the
      mechanical activity of the intestinal muscle, NO production presumably plays a
      substantial role in the action of FMRFa, at least in the initial phase. Our
      biochemical data indicate a direct involvement of FMRFa in NO biosynthesis. FMRFa
      might be hydrolyzed by extracellular peptidases and then the locally released
      arginine might be transported into the cells and broken-down to produce NO.
      Depolarization-induced NO production attributable to the activation of amiloride
      sensitive Na+ channels might also be involved.

PMID- 16612630
TI  - Multiple sources of non-embryonic multipotent stem cells: processed lipoaspirates
      and dermis as promising alternatives to bone-marrow-derived cell therapies.
AB  - A body of evidence points to the existence of stem cell stores in adult tissues,
      in addition to the well-known hematopoietic stem cells from bone marrow. Many
      reports describe the ability of these multipotent cells (developmentally non
      compromised with their organs of origin) to give rise to many different cell
      types in response to specific stimuli. This apparent plasticity provides new
      perspectives in tissue engineering and suggests the usefulness of these cells in
      future protocols of autologous transplantation, gene therapy, and tissue
      reconstitution in a number of pathological processes. Lipoaspirates and dermis
      represent accessible sources for obtaining such cells, with minimal discomfort to
      the donor, and might be promising candidates for cell therapy procedures once
      their features are experimentally accessed. The intention of the present work has
      been to gather reports on the phenotypic characteristics, profile, and plastic
      potential of these stem cells.

PMID- 16612631
TI  - Sex categorization of conspecific pictures in Japanese monkeys (Macaca fuscata).
AB  - We investigated whether monkeys discriminate the sex of individuals from their
      pictures. Whole-body pictures of adult and nonadult monkeys were used as stimuli.
      Two male Japanese monkeys were trained for a two-choice sex categorization task
      in which each of two choice pictures were assigned to male and female,
      respectively. Following the training, the monkeys were presented with novel
      monkey pictures, and whether they had acquired the categorization task was
      tested. The results suggested that while monkeys discriminate between the
      pictures of adult males and females, discrimination of nonadult pictures was
      difficult. Partial presentations of the pictures showed that conspicuous and
      sexually characteristic parts (i.e., underbellies including male scrotums or
      breasts including female nipples) played an important role in the sex
      categorization.

PMID- 16612632
TI  - How great apes perform on a modified trap-tube task.
AB  - To date, neither primates nor birds have shown clear evidence of causal knowledge
      when attempting to solve the trap tube task. One factor that may have contributed
      to mask the knowledge that subjects may have about the task is that subjects were
      only allowed to push the reward away from them, which is a particularly difficult
      action for primates in certain problem solving situations. We presented five
      orangutans (Pongo pygmaeus), two chimpanzees (Pan troglodytes), two bonobos (Pan
      paniscus), and one gorilla (Gorilla gorilla) with a modified trap tube that
      allowed subjects to push or rake the reward with the tool. In two additional
      follow-up tests, we inverted the tube 180 degrees rendering the trap
      nonfunctional and also presented subjects with the original task in which they
      were required to push the reward out of the tube. Results showed that all but one
      of the subjects preferred to rake the reward. Two orangutans and one chimpanzee
      (all of whom preferred to rake the reward), consistently avoided the trap only
      when it was functional but failed the original task. These findings suggest that
      some great apes may have some causal knowledge about the trap-tube task. Their
      success, however, depended on whether they were allowed to choose certain tool
      using actions.

PMID- 16612633
TI  - Atypical spherical deposition on vitreoretinal interface associated with
      toxoplasmic chorioretinitis.
AB  - PURPOSE: To report the clinical and optical coherence tomography features of
      spherical deposits associated with recurrent toxoplasmic chorioretinitis.
      METHODS: Case report. RESULTS: Atypical, 100 microm to 150 microm, greyish
      deposits appeared along retinal arteries and veins as well as on the
      vitreoretinal interface in the macula of a 44-year-old Caucasian woman while she
      was being treated for recurrent toxoplasmic chorioretinitis with antiparasitic
      drugs and subconjunctival injection of betamethasone. They disappeared
      progressively with the systemic use of corticosteroids. Their clinical course was
      nicely documented by optical coherence tomography. CONCLUSIONS: Greyish spherical
      deposits on the vitreoretinal interface have been previously described as
      inflammatory reactions in asymptomatic human T-lymphotropic virus type I (HTLV-1)
      carriers and in patients with HTLV-1-associated uveitis. For the first time,
      optical coherence tomography (OCT) provided clinical correlation of this unusual
      presentation of toxoplasmic chorioretinitis.

PMID- 16612634
TI  - Periocular abscess caused by Pseudallescheria boydii after a posterior subtenon
      injection of triamcinolone acetonide.
AB  - BACKGROUND: A posterior subtenon injection of triamcinolone acetonide is an
      alternative to intravitreal injection in diabetic macular edema and is known to
      have fewer vision-threatening complications. Here, we report a case of periocular
      abscess following posterior subtenon injection of triamcinolone. METHODS: A 62
      year-old woman who had diabetic macular edema and disc neovascularization
      underwent a posterior subtenon injection of triamcinolone acetonide and
      panretinal laser photocoagulation. One month later a periocular abscess was noted
      in the inferotemporal area adjacent to the scleral wall. Pus was removed by fine
      needle aspiration, and microbiologic cultures identified Pseudallescheria boydii.
      The patient was given systemic and subconjunctival treatment with itraconazole.
      However, conjunctival infection and anterior chamber inflammation worsened, and
      another posterior subtenon abscess was found. RESULTS: Despite long-term systemic
      and topical itraconazole therapy, retinal detachment and vitreous opacity were
      shown on B-scan, and atrophic bulbi resulted. CONCLUSIONS: Pseudallescheria
      boydii infection of the eye and orbit can result in a poor visual outcome. Prompt
      surgical debridement and drainage of the abscess, along with appropriate
      antifungal therapy based on susceptibility testing, must be mandatory.

PMID- 16612635
TI  - Intraretinal and periretinal pathology in anterior proliferative
      vitreoretinopathy.
AB  - OBJECTIVES: To determine the intraretinal and periretinal pathological changes in
      early anterior proliferative vitreoretinopathy (APVR). DESIGN: Observational case
      series. PARTICIPANTS: Eighteen patients undergoing retinectomy for APVR. METHODS:
      Retinectomy specimens removed at vitrectomy surgery were analysed by (a) semithin
      light microscopy, (b) immunohistochemistry and (c) electron microscopy. RESULTS:
      The specimens showed consistent outer retinal degenerative changes, marked Muller
      cell hypertrophy and glial continuity to epiretinal membranes. Photoreceptor
      outer and inner segments were markedly disrupted and occasional photoreceptor
      nuclear had pyknosis and chromatin clumping consistent with apoptosis. Muller
      cells expressed upregulated levels of glial fibrillary acid protein (GFAP) and
      extended through glial bridges to complex epiretinal membranes which in some
      areas had a bilaminar structure with a glial-negative inner lamina. CONCLUSION:
      Retinal degeneration and photoreceptor apoptosis occur in retinal detachment
      complicated by proliferative vitreoretinopathy (PVR), although during the early
      stages of the process neural retinal cells remain present, suggesting potential
      for recovery. The intraretinal glial response appears to be centrally involved in
      the formation of contractile epiretinal membranes. The retina retains the
      capacity for a degree of functional recovery following surgery for PVR. Surgical
      separation of anterior epiretinal membranes in PVR may be difficult and
      incomplete and alternative surgical strategies may be necessary to prevent
      recurrence.

PMID- 16612636
TI  - Dysfunction of transmission in the inner retina: incidence and clinical causes of
      negative electroretinogram.
AB  - BACKGROUND: Only limited data exist on the incidence of negative
      electroretinograms (ERG) in clinical practice. The purpose of this study is
      therefore to determine the incidence and clinical causes of a negative ERG in a
      tertiary care centre focused on inherited and acquired retinal degenerations.
      METHODS: All ERGs recorded (in accordance with ISCEV standards) in our
      electrophysiological laboratory from 1992 to 2004 were retrospectively reviewed.
      The negative ERGs (criterion: ERG with b:a wave ratio<or=1 in the scotopic
      standard combined response in at least one eye) were analysed in the context of
      further clinical results. The photopic ON- and OFF-responses were recorded with
      long duration (200 ms) stimuli. RESULTS: A total of 1999 ERGs from 1644 patients
      were performed during the study period. 47/1644 patients (2.9%) presented with a
      negative ERG and were included in the study. Clinical diagnoses included
      inherited retinal dystrophies [X-linked congenital retinoschisis (XRS) (n=17),
      congenital stationary night blindness (CSNB) (n=6), retinitis pigmentosa (RP)
      (n=6), cone (-rod) dystrophy (n=5), choroideremia (n=1), Muller cell sheen
      dystrophy (MCSD) (n=1)] and acquired retinopathies (melanoma-associated
      retinopathy (MAR) (n=1), vigabatrin retinotoxicity (n=1)). In nine patients a
      definitive diagnosis could not be established. Unilateral negative ERGs were seen
      in 10/37 patients where ERG was bilaterally recorded. The fellow eye presented
      with a b:a wave ratio >1 (8 eyes) or ERG responses were not detectable (2 eyes).
      Photopic ON- and OFF-responses were recorded in 38 eyes of 29 patients and 32/38
      eyes presented with a negative ERG. The ON-response was reduced in 25/32 eyes,
      whereas the OFF-response was reduced in only 11/32 eyes. CONCLUSIONS: The
      incidence of a negative ERG can differ between the laboratories depending on the
      causes for ERG recording and was in our laboratory 2.9% in a consecutive series
      of patients with inherited or acquired retinal degenerations. A disorder
      characteristically associated with negative ERG (e.g. XRS, CSNB, MAR) was
      diagnosed in 53% of these patients, whereas in 47% the negative ERG indicated an
      unexpected post-receptoral dysfunction, e.g. in cone (-rod) dystrophy or RP. The
      ON-bipolar pathway was affected in most cases.

PMID- 16612637
TI  - Genotype-phenotype correlation and longitudinal course in ten families with Best
      vitelliform macular dystrophy.
AB  - AIM: Longitudinal course and genotype-phenotype correlation in patients and
      carriers with heterozygous mutations in hBEST1 (bestrophin). METHODS: Thirteen
      patients and seven possible carriers were characterised by mutation analysis with
      SSCPA and direct sequencing, clinical examination and fundus autofluorescence
      (AF). Electrophysiology (EOG and mfERG) and optical coherence tomography (OCT)
      were additionally performed whenever possible. RESULTS: We identified seven
      different heterozygous mutations in ten unrelated families with Best disease.
      I296del was the most frequent mutation. Five of nine individuals with I295del and
      two of three with N99K were asymptomatic carriers. One patient with I295del
      mutation had funduscopically unilateral Best disease. In three children (all with
      I295del), EOG initially showed a clearly present light peak that deteriorated
      during 5 years of follow-up in two of them. Increased AF corresponded well to
      funduscopically visible lesions. During 3-6 years of follow-up, the lesion area
      did not change significantly, but there were obvious changes in the inner
      structure of the lesion. CONCLUSION: In the present series I295del, the most
      frequent mutation in our study, and N99K showed reduced penetrance. EOG was
      normal in young patients even if prime signs were visible. The lesion area did
      not depend on the mutation and did not correlate with VA. Lower VA was associated
      with a more irregular AF pattern due to scarring or haemorrhage. Our results
      indicate a disease causing effect that is cumulative over time.

PMID- 16612638
TI  - Collagen XVIII/endostatin shows a ubiquitous distribution in human ocular tissues
      and endostatin-containing fragments accumulate in ocular fluid samples.
AB  - BACKGROUND: The endostatin domain of type XVIII collagen (ColXVIII) inhibits
      neovascularization and regulates cell migration and matrix turnover. This study
      was designed to demonstrate the protein and gene expression patterns of
      ColXVIII/endostatin in the human eye and to ascertain whether endostatin is
      detectable in ocular fluid samples. METHODS: Twenty human eyes enucleated on
      account of choroidal melanoma were used for immunohistochemical stainings with
      antibodies against ColXVIII and endostatin. In situ hybridization was used to
      localize cells responsible for the production of mRNA for ColXVIII. Tear fluid,
      aqueous humor, and vitreous gel samples were used for Western immunoblotting to
      detect endostatin fragments in these samples. RESULTS: ColXVIII was
      immunolocalized to almost all ocular structures, namely the basement membranes
      (BMs) of the corneal and conjunctival epithelia, Descement's membrane, the
      anterior border layer and posterior pigmented epithelium of the iris, the BMs of
      the pigmented and non-pigmented ciliary epithelia, the internal wall of Schlemm's
      canal and trabeculae, the ciliary and iris muscle cells, the BMs of the pigment
      epithelium of the retina, and the internal limiting membrane. Universal
      expression was seen in the BMs of vascular endothelial cells, and in fibroblasts
      located in the conjunctiva, the iris, and the ciliary body. Endostatin showed a
      corresponding pattern, but additional immunostaining was present in the corneal
      and conjunctival epithelial cells. Most epithelial and mesenchymal cells
      expressed the mRNA for ColXVIII. Endostatin-containing fragments varying in size
      were detected in tear fluid, aqueous humor and vitreous gel samples. CONCLUSIONS:
      Practically all structures of the human eye contain ColXVIII/endostatin,
      emphasizing its possible important structural and functional role in the human
      eye. Furthermore, ocular fluid samples contain endostatin fragments, which may
      contribute to the antiangiogenic properties of the eye.

PMID- 16612639
TI  - Comparison of intact and denuded amniotic membrane as a substrate for cell
      suspension culture of human limbal epithelial cells.
AB  - BACKGROUND: We have previously developed a limbal epithelial culture system using
      a cell-suspension method on denuded amniotic membrane (AM). However, other
      workers reported that intact AM is advantageous for limbal epithelial culture in
      that it preserves stem cell characteristics. In this study, we cultivated human
      limbal epithelial cell-suspensions on both intact and denuded AM and compared the
      morphology and adhesion of the limbal epithelial cells on these two substrates.
      METHODS: Human limbal epithelial cells were dissociated from donor eyes using
      dispase and gentle pipetting and then seeded onto intact and denuded AM as cell
      suspension. Limbal epithelial cells on AM were co-cultured with a MMC-treated 3T3
      fibroblast feeder layer and epithelial differentiation was promoted by air
      lifting. Cultures were examined by light, scanning and transmission electron
      microscopy and differences in cellular attachments and intercellular spacing were
      quantified. Basement membrane complexes were examined by indirect
      immunofluorescence. RESULTS: Limbal cells grown on denuded AM were well
      stratified and differentiated. Cells were well attached to each other and to the
      basement membrane. In contrast, limbal cells cultured on intact AM failed to
      stratify and in places formed a monolayer. The culture on denuded AM had
      significantly (P<0.001) more desmosomal junctions as well as significantly
      (P<0.001) more junctional attachments to the carrier than the intact culture. In
      addition, the intercellular spaces between cells cultivated on denuded AM were
      significantly (P<0.001) smaller than those between cells grown on the intact
      substrate. In cultures on both denuded and intact AM, the basement membrane zone
      displayed a positive staining for collagen VII, integrins alpha-6 and beta-4 and
      laminin 5. CONCLUSIONS: We successfully cultivated well-stratified and 
      differentiated limbal cells on denuded AM, while on the intact AM limbal cells
      failed to stratify and in places formed only a monolayer of cells. The limbal
      cells cultivated on denuded AM were well attached to the AM stroma and were
      morphologically superior to the limbal epithelium cultivated on intact AM. We
      conclude that for purposes of transplantation of differentiated epithelial
      sheets, denuded AM is probably the more practical carrier for human limbal
      epithelial cell cultures when using our cell-suspension culture system.

PMID- 16612640
TI  - Efficient transient expression of human GM-CSF protein in Nicotiana benthamiana
      using potato virus X vector.
AB  - The human granulocyte macrophage colony-stimulating factor (GM-CSF) is a
      glycoprotein with important clinical applications for the treatment of
      neutropenia and aplastic anemia and reducing infections associated with bone
      marrow transplants. We evaluated the potential for using a potato virus X (PVX)
      viral vector system for efficient expression of the biologically functional GM
      CSF protein in Nicotiana benthamiana leaves. The GM-CSF gene was cloned into PVX
      viral expression vector, driven with the CaMV 35S promoter. Gene transfer was
      accomplished by inoculating N. benthamiana leaves with the plasmid DNA of PVX
      vector containing the GM-CSF gene. The expression level of the recombinant GM-CSF
      protein was determined with ELISA and its size was confirmed by Western blot
      analysis. The results showed that: (1) leaf age significantly affects GM-CSF
      protein concentration with younger leaves accumulating 19.8 mg g(-1) soluble
      protein which is 2.6 times the concentration in older leaves, (2) recombinant
      protein accumulation within a given leaf declined slightly over time but was not
      significantly different between 7 and 11 days post-inoculation (dpi), and (3) the
      two leaves immediately above the inoculated leaves play an important role for GM
      CSF accumulation in the younger leaves. Protein extracts of infected N.
      benthamiana leaves contained recombinant human GM-CSF protein in concentrations
      of up to 2% of total soluble protein, but only when the pair of leaves
      immediately above the inoculated leaves remained intact. The recombinant protein
      actively stimulated the growth of human TF-1 cells suggesting that the
      recombinant human GM-CSF expressed via PVX viral vector was biologically active.

PMID- 16612641
TI  - An accumulation of tandem DNA repeats on the Y chromosome in Silene latifolia
      during early stages of sex chromosome evolution.
AB  - Sex chromosomes in mammals are about 300 million years old and typically have a
      highly degenerated Y chromosome. The sex chromosomes in the dioecious plant
      Silene latifolia in contrast, represent an early stage of evolution in which
      functional X-Y gene pairs are still frequent. In this study, we characterize a
      novel tandem repeat called TRAYC, which has accumulated on the Y chromosome in S.
      latifolia. Its presence demonstrates that processes of satellite accumulation are
      at work even in this early stage of sex chromosome evolution. The presence of
      TRAYC in other species of the Elisanthe section suggests that this repeat had
      spread after the sex chromosomes evolved but before speciation within this
      section. TRAYC possesses a palindromic character and a strong potential to form
      secondary structures, which could play a role in satellite evolution. TRAYC
      accumulation is most prominent near the centromere of the Y chromosome. We
      propose a role for the centromere as a starting point for the cessation of
      recombination between the X and Y chromosomes.

PMID- 16612642
TI  - A founder effect and mutational hot spots may contribute to the most frequent
      mutations in the SPG3A gene.

PMID- 16612643
TI  - The transverse placement laminoplasty using titanium miniplates for the
      reconstruction of the laminae in thoracic and lumbar lesion.
AB  - Laminoplasty for thoracic and lumbar spine surgery enables surgeons to preserve
      the posterior arch of the spine while preventing invasion of hematoma and scar
      tissue, postoperative instability, subluxation, and kyphotic deformities. The
      authors have developed a new surgical technique: namely, transverse placement
      laminoplasty (TPL) using titanium miniplates. Eight patients and 18 laminae
      underwent TPL using a titanium mini-plate. The preoperative diagnoses were six
      intradural tumors, one ossification of a yellow ligament and one spontaneous
      spinal cord herniation. The mean blood loss was 219 g and the mean duration of
      surgery was 3 h and 54 min. The mean postoperative follow-up period was 2 years
      and 1 month. All eight patients started to sit with a soft brace within the
      second postoperative day, and were able to walk within the fifth postoperative
      day. There were no cases of spinal deformity, an invasion of hematoma or scar
      tissue into the spinal canal on magnetic resonance imaging, or back pain. TPL
      simultaneously enables surgeons to obtain sufficient field of vision and rigid
      early fixation of the reduced lamina at the time of surgery. Moreover, our novel
      technique also simplifies the postoperative treatment, while preserving the
      posterior arch of the spine, and also preventing an invasion of a hematoma and
      scar tissue, postoperative instability, subluxation, and kyphotic deformities.

PMID- 16612644
TI  - [Old drugs and new approval procedures: Akrinor remains marketable and an
      application for reapproval of Arginin Vasopressin has been made].

PMID- 16612645
TI  - [Chemotherapy of testicular cancer].
AB  - Platinum-based polychemotherapy has increased the cure rate in testicular cancer
      dramatically: at first, chemotherapy was mainly used in advanced disease.
      Recently it has also become common in low-stage disease, though other therapeutic
      options are equivalent. Risk factors might help to find the right decision. The
      success of treatment in patients with metastatic disease results from the
      combination of chemotherapy and secondary surgery. High-dose chemotherapy for
      patients with poor prognosis or recurrent disease is being evaluated in clinical
      trials. Concerning the success in these stages prognostic factors are of special
      importance. Patients with advanced-stage nonseminoma need residual tumor
      resection after chemotherapy if no complete remission could be achieved. The
      therapist should be aware of the indication for and schedule of chemotherapy, its
      side effects, and supportive care.

PMID- 16612646
TI  - Determinants of repeated-sprint ability in females matched for single-sprint
      performance.
AB  - This study investigated the relationship between VO2max and repeated-sprint
      ability (RSA), while controlling for the effects of initial sprint performance on
      sprint decrement. This was achieved via two methods: (1) matching females of low
      and moderate aerobic fitness (VO2max: 36.4 +/- 4.7 vs 49.6 +/- 5.5 ml kg(-1) min(
      1) ; p < 0.05) for initial sprint performance and then comparing RSA, and (2)
      semi-partial correlations to adjust for the influence of initial sprint
      performance on RSA. Tests consisted of a RSA cycle test (5 x 6-s max sprints
      every 30 s) and a VO2max test. Muscle biopsies were taken before and after the
      RSA test. There was no significant difference between groups for work (W1, 3.44
      +/- 0.57 vs 3.58 +/- 0.49 kJ; p = 0.59) or power (P1, 788.1 +/- 99.2 vs 835.2 +/-
      127.2 W; p = 0.66) on the first sprint, or for total work (W(tot), 15.2 +/- 2.2
      vs 16.6 +/- 2.2 kJ; p = 0.25). However, the moderate VO2max group recorded a
      smaller work decrement across the five sprints (W(dec), 11.1 +/- 2.5 vs 7.6 +/-
      3.4%; p = 0.045). There were no significant differences between the two groups
      for muscle buffer capacity, muscle lactate or pH at any time point. When a semi
      partial correlation was performed, to control for the contribution of W1 to
      W(dec), the correlation between VO2max and W(dec) increased from r = -0.41 (p >
      0.05) to r = -0.50 (p < 0.05). These results indicate that VO2max does contribute
      to performance during repeated-sprint efforts. However, the small variance in
      W(dec) explained by VO2max suggests that other factors also play a role.

PMID- 16612647
TI  - Congenital absence of the portal vein in a child with Turner syndrome.
AB  - Congenital absence of the portal vein (CAPV) is a rare malformation associated
      with hepatic encephalopathy and liver function abnormalities. We report a case of
      a 2-year-old with Turner syndrome, CAPV, and congenital heart malformations.

PMID- 16612648
TI  - Construction of BAC and BIBAC libraries from sunflower and identification of
      linkage group-specific clones by overgo hybridization.
AB  - Complementary BAC and BIBAC libraries were constructed from nuclear DNA of
      sunflower cultivar HA 89. The BAC library, constructed with BamHI in the pECBAC1
      vector, contains 107,136 clones and has an average insert size of 140 kb. The
      BIBAC library was constructed with HindIII in the plant-transformation-competent
      binary vector pCLD04541 and contains 84,864 clones, with an average insert size
      of 137 kb. The two libraries combined contain 192,000 clones and are equivalent
      to approximately 8.9 haploid genomes of sunflower (3,000 Mb/1C), and provide a
      greater than 99% probability of obtaining a clone of interest. The frequencies of
      BAC and BIBAC clones carrying chloroplast or mitochondrial DNA sequences were
      estimated to be 2.35 and 0.04%, respectively, and insert-empty clones were less
      than 0.5%. To facilitate chromosome engineering and anchor the sunflower genetic
      map to its chromosomes, one to three single- or low-copy RFLP markers from each
      linkage group of sunflower were used to design pairs of overlapping
      oligonucleotides (overgos). Thirty-six overgos were designed and pooled as probes
      to screen a subset (5.1x) of the BAC and BIBAC libraries. Of the 36 overgos, 33
      (92%) gave at least one positive clone and 3 (8%) failed to hit any clone. As a
      result, 195 BAC and BIBAC clones representing 19 linkage groups were identified,
      including 76 BAC clones and 119 BIBAC clones, further verifying the genome
      coverage and utility of the libraries. These BAC and BIBAC libraries and linkage
      group-specific clones provide resources essential for comprehensive research of
      the sunflower genome.

PMID- 16612650
TI  - Mozart: a metropolitan legend with pediatric neurosurgical implications.

PMID- 16612649
TI  - Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic
      antifolates.
AB  - Cellular uptake of hydrophilic antifolates proceeds via the reduced folate
      carrier whereas lipophilic antifolates enter cells by diffusion. Recently we have
      shown that transfectant cells overexpressing the mutant G482 ABCG2 displayed 120
      6,250-fold resistance to hydrophilic antifolates than untransfected cells upon 4
      h drug exposure, but lost almost all their antifolate resistance upon 72 h drug
      exposure (Shafran et al. in Cancer Res 65:8414-8422, 2005). Here we explored the
      ability of the wild type (WT) R482-as well as the mutant G482-and T482 ABCG2 to
      confer resistance to lipophilic antifolate inhibitors of dihydrofolate reductase
      (trimetrexate, piritrexim, metoprine and pyrimethamine) and thymidylate synthase
      (AG337, AG377 and AG331). Lipophilic antifolate resistance was determined using
      growth inhibition assays upon 72 h drug exposure. Cells overexpressing these
      mutant efflux transporters displayed up to 106-fold resistance to lipophilic
      antifolates relative to untransfected cells; this resistance was reversed by the
      specific and potent ABCG2 efflux inhibitor Ko143. In contrast, cells
      overexpressing the WT R482 ABCG2 exhibited either no or only a low-level of
      lipophilic antifolate resistance. These results provide the first evidence that
      overexpression of the mutant G482- and T482 but not the WT R482 ABCG2 confers a
      high-level of resistance to lipophilic antifolates. The high membrane
      partitioning of lipophilic antifolates along with the large confinement of ABCG2
      to the plasma membrane suggest that these mutant ABCG2 transporters may possibly
      recognize and extrude lipophilic antifolates from the lipid bilayer. The
      potential implications to cancer chemotherapy as well as the mechanism of
      anticancer drug extrusion by these mutant exporters are discussed.

PMID- 16612651
TI  - Monogenea of marine fishes from Hainan Island, China. VIII. Two new species of
      Euryhaliotrema Kritsky & Boeger, 2002 (Dactylogyridae) from Lutjanus
      argentimaculatus (Teleostei: Lutjanidae).
AB  - This paper reports two new species of Euryhaliotrema Kritsky & Boeger, 2002
      collected from the gills of Lutjanus argentimaculatus (Forsskal). E. xinyingense
      n. sp. is similar to Euryhaliotrema atlanticum Kritsky & Boeger, 2002 in the
      structure of copulatory apparatus, but differs from the latter in the shape of
      anchors and the structure of vagina. E. hainanense n. sp. also closely resembles
      E. atlanticum Kritsky & Boeger, 2002, but differs from the latter in the
      structure of haptor and the shape of accessory piece.

PMID- 16612652
TI  - A new species of Aberrapex Jensen, 2001 (Cestoda: Lecanicephalidea) from Taeniura
      lymma (Forsskal) (Myliobatiformes: Dasyatidae) from off Sabah, Malaysia.
AB  - A new lecanicephalidean species of Aberrapex Jensen, 2001 is described from the
      blue-spotted fantail ray Taeniura lymma (Forsskal) collected off the eastern
      coast of Sabah in Malaysian Borneo. This is the first record of a
      lecanicephalidean tapeworm from the island of Borneo and the first record of
      Aberrapex from this host species. A. manjajiae n. sp. is easily distinguished
      from its two congeners, A. senticosus Jensen, 2001 and A. arrhynchum (Brooks,
      Mayes & Thorson, 1981) Jensen, 2001, based on its overall smaller size (928-1,971
      vs 1,485-6,333 and up to 3,350 microm long, respectively) and fewer testes (10-19
      vs 20-40 and 18-25, respectively). In addition, A. manjajiae n. sp. is readily
      distinguished from A. senticosus based on a more anteriorly positioned genital
      pore (76-85 vs 52-72% of proglottid length from posterior end) and its distal
      bothridial microthrix pattern. A. manjajiae n. sp. can be further distinguished
      from A. arrhynchum based on its smaller scolex (82-101 x 119-164 vs 177-186 x 233
      326 microm). The host distribution of Aberrapex is expanded from the Myliobatidae
      to include the Dasyatidae.

PMID- 16612653
TI  - Two new species of Eutrombidium Verdun, 1909 (Acari: Prostigmata: Eutrombidiidae)
      from Asia and a new host record for this genus.
AB  - Two new species of larval mites are described Eutrombidium laosanum n. sp.
      ectoparasitic on undetermined Gryllidae (Orthoptera) from Laos and Indonesia
      (Lingga Islands) and E. sigirijanum n. sp. ectoparasitic on undetermined
      Tenebrionidae (Coleoptera) from Sri Lanka.

PMID- 16612654
TI  - The phylogenetic position of Ixodes stilesi Neumann, 1911 (Acari: Ixodidae):
      morphological and preliminary molecular evidences from 16S rDNA sequences.
AB  - The female of Ixodes stilesi Neumann, 1911 (Acari Ixodidae) is redescribed and
      the male and nymph are described from specimens collected from Pudu puda (Molina)
      (Artiodactyla: Cervidae) in Chile. Both sexes of I. stilesi have characteristics
      of the subgenera Ixodes Latreille, 1795 and Ixodiopsis Filippova, 1957. The
      females of I. stilesi are peculiar in having the combination of the sinuous
      scutum outline, rounded porose areas with distinct borders separated by the width
      of one area, slender and long palpi, and two subequal spurs on coxa I. The male
      is unique in having a combination of a posteriorly wrinkled marginal folder, a
      basis capituli longer than wide, a non-crenulate hypostome toothed portion, two
      spurs on coxa II to IV and the presence of a pseudoscutum. The nymph of I.
      stilesi has blunt anterior and posterior processes on palpal article I
      (characteristics of the subgenus Ixodiopsis and some Pholeoixodes Schulze, 1942)
      and a wing-shaped basis capituli with a prominent triangular cornua. Phylogenetic
      analyses based on 16S mitochondrial rDNA sequences of 12 Neotropical and two
      Australian Ixodes species, plus three argasids, were carried out to clarify the
      position of I. stilesi. The results of phylogenetic analyses and morphological
      characters indicate a close relationships between I. stilesi and two other
      Neotropical species of uncertain subgeneric status, I. neuquenensis Ringuelet,
      1947 and I. sigelos Keirans, Clifford & Corwin, 1976.

PMID- 16612655
TI  - Leucocytozoon atkinsoni n. sp. (Apicomplexa: Leucocytozoidae) from the avian
      family Timaliidae.
AB  - Investigators of haematozoa of the Timaliidae have reported the presence of two
      species of Leucocytozoon Berestneff, 1904, i.e. L. liothricis Laveran & Marullaz,
      1914 and L. timaliae Bennett, Earle & Pierce, 1993. Blood films collected from 42
      wild-caught babblers in Madagascar were stained and examined for the presence of
      haematozoa using a compound microscope. To date, no species of avian haematozoa
      have been reported from babblers in Madagascar, although haematozoa have been
      observed. In the present study, we report a new species of Leucocytozoon, L.
      atkinsoni n. sp., whose morphometrics fall between those reported for the two
      previously described species from timaliids. The parasite is capped by the host
      cell nucleus covering 38% of its perimeter. L. atkinsoni n. sp. was found to have
      a marked, intensely staining, nucleolus as well as vacuoles in the parasite
      cytoplasm, in contrast to both L. liothricis and L. timaliae. Remnants of the
      host cell cytoplasm are commonly observed in cells infected with L. atkinsoni, a
      characteristic not reported in association with either of the previously
      described species from these hosts.

PMID- 16612656
TI  - Seven new species of Eimeria Schneider, 1875 (Apicomplexa: Eimeriidae) from
      colubrid snakes of Guatemala and a discussion of what to call ellipsoid
      tetrasporocystic, dizoic coccidia of reptiles.
AB  - During a survey of Guatemalan herpetofauna in the summers of 1998-2000, 29
      presumed new species of Eimeria Schneider, 1875 were found, seven of which have a
      distinct elongate-ellipsoidal shape (L/W ratio >or= 1.7) and are described
      herein. Six of the seven new species are similar in oocyst length, width and L/W
      ratio and sporocyst length, width and L/W ratio, lack a micropyle, oocyst
      residuum, Stieda body, sub-- and parastieda bodies, have a polar granule and
      sporocyst residuum, and their sporocysts appear to have dehiscence sutures. The
      seventh is slightly smaller and has sporocysts with a Stieda body. The new
      species are: E. coniophanes n. sp - whose sporulated oocysts from Coniophanes
      fissidens are 29.2x14.9 (27-31x13-16) microm, with sporocysts 10.0 x 7.8 microm;
      E. coniophis n. sp. -from Conophis lineatus are 32.0x16.5 (30-34x14-18) microm,
      with sporocysts 10.2 x 8.9microm; E. dryomarchoni n. sp. - from Drymarchon corais
      are 32.2x17.7 (31-34x17-19) microm, with sporocysts 10.7 x 8.6 microm; E.
      leptophis n. sp. - from Leptophis mexicanus are 29.5x17.0 (28-31x16-18) microm,
      with sporocysts 10.0 x 9.1 microm; E. oxybelis n. sp. - from Oxybelis aeneus are
      31.8x16.5 (29-33x15-18) microm, with sporocysts 10.3 x 8.8 microm; and E.
      scaphiodontophis n. sp. - from Scaphiodontophis annulatus are 30.0x15.3 (28-33x14
      16) microm, with sporocysts 9.9 x 7.9 microm. Sporulated oocysts of E. siboni n.
      sp. from Sibon nebulata are 24.3x14.2 (21-27x13-16) microm, with sporocysts 10.0
      x 7.1 microm and with a Stieda body. We conclude that until all aspects of each
      life-cycle are known, it is prudent at this time to name all tetrasporocystic
      dizoic coccidia from snakes as members of Eimeria rather than place some of them
      in Choleoeimeria Paperna & Landsberg, 1989.

PMID- 16612657
TI  - Neotropical Monogenoidea. 49. Four new species of the Diplectanidae
      (Dactylogyrinea) from the gills of some pachyurines (Teleostei: Sciaenidae) from
      the Rio Tocantins and Rio Doce Basins, with the proposal of Anoplectanum n. g.
      and Spinomatrix n. g.
AB  - Four new species of the Diplectanidae from the gills of freshwater sciaenid
      species (Pachyurinae) in Brazil are described and two new genera, Anoplectanum n.
      g. and Spinomatrix n. g., are proposed. These are: Diplectanum copiosum n. sp.
      from Pachyurus junki and Petilipinnis grunniens; Anoplectanum haptorodynatum n.
      g., n. sp. from Pachyurus junki and Petilipinnis grunniens, and A. microsoma n.
      g., n. sp. from Petilipinnis grunniens, all in the Tocantins Basin; and
      Spinomatrix penteormos n. g., n. sp. from Pachyurus adspersus in the Rio Doce
      Basin. Anoplectanum is proposed to accommodate diplectanids lacking squamodiscs
      and having a superficial root of the ventral anchor as long or longer than the
      deep root. Spinomatrix is proposed for species having a haptoral and peduncular
      armature composed of spines, hooks, anchors, squamodiscs and armed muscular pads.

PMID- 16612658
TI  - Redescription and new data on Microsomacanthus jaegerskioeldi (Fuhrmann, 1913)
      (Cestoda: Hymenolepididae).
AB  - Microsomacanthus jaegerskioeldi (Fuhrmann, 1913) is redescribed and illustrated
      on the basis of type-material from Somateria mollissima captured in the vicinity
      of Goteborg (Sweden) and specimens from the same host from the Barents Sea, off
      Iceland and in the East Siberian Sea. A lectotype is designated and an amended
      diagnosis is provided. Previous reports of this parasite in various hosts and
      localities are discussed, and the geographical distribution and host range of the
      species are updated.

PMID- 16612659
TI  - Neoascarophis macrouri n. sp. (Nematoda: Cystidicolidae) from the stomach of
      Macrourus berglax (Macrouridae) in the eastern Greenland Sea.
AB  - A new species of parasitic nematode, Neoascarophis macrouri n. sp.
      (Cystidicolidae), is described from the stomach and stomach wall of the marine
      deep-water fish Macrourus berglax (onion-eye grenadier) in the eastern Greenland
      Sea (North Atlantic Ocean). The new species, studied using both light and
      scanning electron microscopy, is characterised mainly by the location of the
      vulva near the posterior end of the body (a short distance anterior to the anus),
      non-filamented eggs, the structure of the mouth, a short vestibule and the length
      of the spicules (567-615 and 144-156 mum). Metabronema insulanum Solov'eva, 1991
      is transferred to Neoascarophis as N. insulana (Solov'eva, 1991) n. comb.

PMID- 16612660
TI  - Thaumatocotyle pseudodasybatis Hargis, 1955 (Monogenea: Monocotylidae) from
      Aetobatus cf. narinari, with a comparison of specimens from Australia, French
      Polynesia and New Caledonia.
AB  - Thaumatocotyle pseudodasybatis Hargis, 1955, has previously been described from
      Aetobatus narinari in the Atlantic and subsequently recorded from the Pacific.
      Aetobatus cf. narinari is now considered a species complex; as monocotylids are
      often strictly species specific, we test the hypothesis that detailed examination
      of specimens of monocotylids from rays from various localities could reveal
      morphological differences and eventually help our understanding of the
      systematics of the host. T. pseudodasybatis, previously known from seven
      specimens only, is redescribed from an additional 26 specimens from the South
      Pacific (off New Caledonia, Australia and Ranguiroa, French Polynesia), all from
      Aetobatus cf. narinari. The female reproductive organs are described in detail.
      The distal extremity of the male sclerotised copulatory organ, described in
      detail for the first time, shows a characteristic pattern of longitudinal
      striations on its edge that might be useful for future distinction from other
      species. The development of the male and female organs in juveniles is described,
      showing that growth of the male sclerotised copulatory organ begins with its
      basal part and precedes development of the ejaculatory bulb. Specimens from New
      Caledonia, Australia and French Polynesia had similar measurements and
      morphology, especially in the shape of the distal end of the male sclerotised
      copulatory organ; they were also similar to the holotype from the Atlantic. This
      suggests that all specimens from the Pacific and Atlantic belong to a single
      species; T. pseudodasybatis thus cannot be used to differentiate populations of
      Aetobatus cf. narinari, perhaps because this monocotylid is not strictly species
      specific.

PMID- 16612661
TI  - Description de deux nouvelles especes de Lamellodiscus Johnston & Tiegs, 1922
      (Monogenea: Diplectanidae) du groupe morphologique 'ignoratus', parasites de
      Diplodus sargus et D. vulgaris (Teleostei: Sparidae).
AB  - The study of the diplectanid gill parasites of Diplodus Rafinesque (Teleostei:
      Sparidae) from off the Algerian coast revealed the presence of several species of
      Lamellodiscus Johnston & Tiegs, 1922 on D. sargus (Linnaeus) and D. vulgaris
      (Geoffroy Saint-Hilaire). Some of these species differ from the others by having
      a copulatory organ "en lyre" and lamellodiscs of the morphological group
      'ignoratus' of Oliver (1987). In Lamellodiscus, the subgroup 'ignoratus',
      proposed by Amine & Euzet (2005), characterised by a simple lateral dorsal bar,
      includes L. ignoratus Palombi, 1943 and L. fraternus Bychowsky, 1957. Two new
      species, L. falcus n. sp. and L. neifari n. sp. form part of the 'ignoratus'
      subgroup. These species are distinguished by the morphology and the size of the
      sclerotised parts of the haptor and copulatory organ.

PMID- 16612662
TI  - Terranova galeocerdonis (Thwaite, 1927) (Nematoda: Anisakidae) from Carcharias
      taurus (Chondrichthyes: Odontaspididae) off Argentina, with comments on some
      related species.
AB  - The purpose of this study was to study and redescribe Terranova galeocerdonis
      (Thwaite, 1927) from Carcharias taurus off Argentina. Its fourth larval stage was
      described, measured and illustrated for the first time. The host and geographical
      range of this species is extended into the southwestern Atlantic Ocean. When the
      present material was compared with T. rochalimai (Pereira, 1935) and T.
      ginglymostomae Olsen, 1952, it was considered that both morphological and
      morphometrical differences between the three species did not justify
      differentiation at the specific level. As a result, T. rochalimai and T.
      ginglymostomae are considered to be junior synonyms of T. galeocerdonis.

PMID- 16612663
TI  - Monogeneans from the gills of glassfishes (Teleostei: Perciformes: Ambassidae) in
      India, with the proposal of Chandacleidus n. g. (Monogenea: Dactylogyridae).
AB  - Chandacleidus n. g. (Monogenea, Dactylogyridae) is proposed to include three
      species collected from the gills of Indian glassfishes (Ambassidae):
      Chandacleidus recurvatus (Jain, 1961) n. comb. (syn. Urocleidus recurvatus Jain,
      1961) from Chanda nama and C. ranga (new host record) is redescribed; and
      Chandacleidus saiensis n. sp. and C. lucknowensis n. sp., both from Chanda nama
      and C. baculis, are described. Chandacleidus n. g. is characterised by species
      possessing: posteriorly united intestinal caeca; overlapping gonads (testis
      dorsal to ovary); a counterclockwise male copulatory organ; a grooved accessory
      piece; a dextro-marginal vaginal pore; a haptor with two lateral flaps and armed
      with dissimilar dorsal and ventral anchor/bar complexes and 14 similar hooks
      (dissimilar in size); and hook shanks comprised of two subunits.

PMID- 16612664
TI  - Multiple evidence for an early age pro-oxidant state in Down Syndrome patients.
AB  - Oxidative stress has been associated with Down syndrome (DS) and with its major
      phenotypic features, such as early ageing. In order to evaluate an in vivo pro
      oxidant state, the following analytes were measured in a group of DS patients
      aged 2 months to 57 years: (a) leukocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG);
      (b) blood glutathione; (c) plasma levels of: glyoxal (Glx) and methylglyoxal
      (MGlx); some antioxidants (uric acid, UA, ascorbic acid, AA and Vitamin E), and
      xanthine oxidase (XO) activity. A significant 1.5-fold increase in 8-OHdG levels
      was observed in 28 DS patients vs. 63 controls, with a sharper increase in DS
      patients aged up to 30 years. The GSSG:GSH x 100 ratio was significantly higher
      in young DS patients (< 15 years), in contrast to DS patients aged >or=15 years
      that showed a significant decrease in the GSSG:GSH x 100 ratio ratio vs. controls
      of the respective age groups. Plasma Glx levels were significantly higher in
      young DS patients, whereas no significant difference was detected in DS patients
      aged >or=15 years. Unlike Glx, the plasma levels of MGlx were found to be
      significantly lower in DS patients vs. controls. A significant increase was
      observed in plasma levels of UA in DS patients that could be related to an
      increased plasma XO activity in DS patients. The plasma concentrations of AA were
      also increased in young (< 15 years) DS patients, but not in older patients vs.
      controls in the same age range. The levels of Vitamin E in DS patients did not
      differ from the values determined in control donors. The evidence for a multiple
      pro-oxidant state in young DS patients supports the role of oxidative stress in
      DS phenotype, with relevant distinctions according to patients' ages.

PMID- 16612665
TI  - A revolution for aging research.
AB  - In the year 1992, two publications on age-specific mortality rates revealed a
      cessation of demographic aging at later ages in very large cohorts of two
      dipteran species reared under a variety of conditions. Despite some initial
      concerns about possible artifacts, these findings have now been amply
      corroborated in the experimental literature. The eventual cessation of aging
      undermines the credibility of simple Gompertzian aging models based on a
      protracted acceleration in age-specific mortality during adulthood. The first
      attempt to explain the apparent cessation of aging was extreme lifelong
      heterogeneity among groups with respect to frailty. This lifelong heterogeneity
      theory assumes an underlying Gompertzian aging affecting every member of an adult
      cohort, with a merely apparent cessation of aging explained in terms of the
      increasing domination of a slowly aging group among the survivors to late ages.
      This theory has received several experimental refutations. The second attempt to
      explain the cessation of aging applied force of natural selection theory. This
      explanation of the cessation of aging has been corroborated in several Drosophila
      experiments. In particular, this theory requires that both age-specific survival
      and age-specific fecundity cease declining in late life, which has now been
      experimentally established. This theory also predicts that the timing of the
      cessation of aging should depend on the last age of reproduction in a
      population's evolutionary history, a prediction that has been corroborated. While
      lifelong heterogeneity should reduce average age-specific mortality in late life
      whenever it is pronounced, the cessation of aging in late life can be explained
      by plateaus in the forces of natural selection whether lifelong heterogeneity is
      present or not. The discovery that aging ceases is one of the most significant
      discoveries in recent aging research, with potentially revolutionary scientific
      implications.

PMID- 16612666
TI  - Interconnections between genetics, ageing, pathology and medicine, as revealed in
      an interview with George Martin. Interview by Robin Holliday.

PMID- 16612667
TI  - Biological cycle of Lorryia formosa (Acari, Tydeidae) on rubber tree leaves: a
      case of thelytoky.
AB  - Lorryia formosa Cooreman has been collected on many different host plants around
      the world. The biological cycle of this species was studied at 28 degrees C with
      mites collected from a rubber tree crop. The life table was constructed based on
      sixty individuals. The average lifetime was 37.43 +/- 20.23 (SE) days, and the
      r(m) was 0.08. The sex ratio was totally female biased, and unfertilized eggs
      developed into females. This is the first record of thelytoky in Tydeoidea proved
      by rearing.

PMID- 16612668
TI  - Anatomical injury induced by the eriophyid mite Aceria anthocoptes on the leaves
      of Cirsium arvense.
AB  - Anatomical injury of the leaves of the invasive species, Cirsium arvense (L.)
      Scop., caused by the eriophyid mite Aceria anthocoptes (Nal.), which is the only
      eriophyid mite that has been recorded on C. arvense worldwide, is described. The
      injury induced by the mite feeding on the leaves of C. arvense results in visible
      russeting and bronzing of the leaves. Other conspicuous deformations are folding
      and distortion of the leaf blade and curling of leaf edge, as well as gradual
      drying of leaves. The anatomical injury of the mature leaves of field-collected
      plants was limited to the epidermis of the lower leaf surface. However, on young
      leaves of experimentally infested plants, rust mite injuries extend to epidermal
      cells on both leaf surfaces and to those of deeper mesophyll layers. On these
      leaves, lesions on the lower leaf surface even affected the phloem of the
      vascular bundles. Leaf damage induced by A. anthocoptes is discussed with regard
      to the mite's potential as a biological control agent of C. arvense.

PMID- 16612669
TI  - Assessment of sublethal effects of clofentezine on life-table parameters in
      Hawthorn spider mite (Tetranychus viennensis).
AB  - A leaf disc bioassay was employed in the laboratory to assess the population
      responses of Tetranychus viennensis Zacher to clofentezine at three
      concentrations (LC(10), LC(25) and LC(50)) in three successive generations. Life
      table parameters were calculated in each acaricide exposure regime and compared
      by jackknife procedures. Clofentezine treatments in the juvenile stages
      significantly delayed development of the mites, and this delay increased with
      increasing dose but decreased as the mites developed. Exposure to clofentezine
      reduced the net reproduction rate (R(0)) in a concentration-dependent manner. The
      LC(50) treatment had strong effects on the hatchability of eggs produced by
      surviving females. Hatch rate dropped from 0.83 in the untreated control to 0.51
      in the third generation. When exposed to constant concentrations of clofentezine
      in three successive generations, the intrinsic rate of increase and R(0) of the
      mites decreased significantly, but they increased significantly when exposed to
      decreasing concentrations. Unexposed offspring of the exposed mother also
      displayed increases in R(0) and the jackknife procedures indicated no significant
      differences in R(0) between LC(10) and LC(25) offspring and their mothers vs. the
      control, while R(0) in unexposed LC(50) offspring was significantly higher than
      their mother's, but lower than that in the control. These changing patterns of
      r(m) reveal that acaricide effects at the population level strongly depend on the
      life-history characteristics of T. viennensis and the chemical mode of action.

PMID- 16612670
TI  - A novel disease affecting the predatory mite Phytoseiulus persimilis (Acari,
      Phytoseiidae): 1. Symptoms in adult females.
AB  - Adult female Phytoseiulus persimilis Athias-Henriot (Acari, Phytoseiidae) of one
      of our laboratory populations showed a lower degree of attraction to herbivore
      induced plant volatiles than other laboratory populations. We hypothesized
      earlier that this consistent change in foraging behavior is a symptom of a
      disease, as it is a contagious phenomenon. Here we describe more symptoms by
      comparing mated females of this population (non-responding (NR) population) with
      mated females of other populations that are strongly attracted to herbivore
      induced plant volatiles (responding populations). The most apparent
      characteristic of the NR population was the presence of numerous dorso-ventrally
      flattened females (76% of all females). These females had a normal size after
      mating but shrank during adulthood. Independent of their age, shrunken females
      did not reproduce and died a few days after shrinking. In addition to these
      profound differences in short term performance, females from the NR-population
      showed behavioral changes, including a lower degree of attraction to herbivore
      induced plant volatiles, a higher tendency to leave a prey-patch and a lower
      predation rate. Moreover, about half of the live females of the NR-population
      carried birefringent dumbbell-shaped crystals in the legs whereas live females of
      a responding population carried crystals only in the lumen of the Malpighian
      tubules and the rectum. The symptom 'crystals in the legs' was correlated with
      low reproduction. Energy dispersive X-ray diffraction of these crystals revealed
      that they contain calcium and phosphorus along with carbon and oxygen. Crystals
      with comparable elemental compositions and the same characteristic concentric
      layering are well known in insects, where they are thought to play a major role
      in detoxification of calcium and heavy metals, and in storage of phosphorus. The
      fraction of predators carrying a white spot in the distal part of the
      opisthosoma, due to accumulation of excretory material in the rectum, was the
      same in both populations. Present results are discussed in the context of mite
      pathology and biological control.

PMID- 16612671
TI  - Side effects of five new acaricides on the predator Galendromus occidentalis
      (Acari, Phytoseiidae).
AB  - Contact and residual effects of etoxazole, spiromesifen, fenpyroximate,
      bifenazate, and acequinocyl on life parameters of Galendromus occidentalis
      (Nesbitt) were studied under laboratory conditions. Fenpyroximate reduced adult
      female longevity to <24 h, and no eggs were laid. Longevity of spiromesifen- and
      acequinocyl-treated adult females was reduced to 4 days, with observed reductions
      in fecundity and fertility. Etoxazole and bifenazate did not reduce adult female
      longevity, but progeny were not produced.

PMID- 16612672
TI  - The distribution and ecological preferences of Boophilus microplus (Acari:
      Ixodidae) in Mexico.
AB  - This paper focuses on the distribution of the cattle tick, Boophilus microplus,
      in Mexico. The study is aimed to understand the climate factors responsible of
      the recorded distribution that can statistically define the suitable habitat for
      the tick. Sites where the tick is recorded display significantly higher values of
      some climate variables in comparison with those where the tick is absent, namely
      mean monthly temperature (T) and atmospheric water vapour (W), yearly accumulated
      T, W and rainfall (R) (p < 0.001 for every variable), with smaller significance
      for the yearly sum of T/R and T/W ratios (p < 0.05). Interestingly, variables
      involving the Normalized Derived Vegetation Index (NDVI) do not shown statistical
      differences between the sites where the tick is present or absent. The best set
      of habitat-defining variables was integrated into a framework to assess the
      habitat suitability for the tick in Mexico. We used a point-to-point similarity
      metric to assign a classification value to a candidate site based on the
      proximity in environmental space of the most similar record site. A combination
      of 7 yearly and monthly values for temperature, rainfall and water vapour
      variables captured the tick distribution. Model performance, as tested with a
      separate set of distribution tests and defined by the AUC value, was 0.89. Causes
      of errors as detected with a visual comparison of both known and predicted
      distribution of the tick may be attributed to the use of a medium resolution,
      unable to capture locally important features of tick distribution, and to
      incomplete collections in some parts of the country.

PMID- 16612673
TI  - Incidence of acneform reactions after laser hair removal.
AB  - There have been several studies published on the side effects of laser hair
      removal, but none specifically looked at acneform reactions. The aim of this
      study is to obtain an accurate assessment of the incidence of acneform reactions
      after laser hair removal in relation to skin type, laser type, site of treatment,
      polycystic ovarian syndrome history (PCOS), age, and sex of the patient. This is
      a multi-centre prospective study of patients presenting for laser hair removal.
      Data were gathered using a questionnaire completed by the staff who performed the
      treatment. The incidence of acneform reactions was 6%. The following variables
      showed a statistically significant effect on the percentage of patients with
      reactions: age, with younger patients more likely to develop lesions; those
      treated with the Nd:YAG laser type were more likely to develop lesions than those
      treated with the alexandrite; and the Fitzpatrick skin type V showed the highest
      incidence of acneform lesions, followed by skin types II and IV. History of PCOS,
      number of prior treatments, use of aloe vera cooling gel, and the sex of the
      patient had no apparent effect on the incidence of acneform lesions. Acneform
      reactions are relatively common after laser hair removal; however, in the
      majority of cases, the severity of the reaction was mild and lasted for a short
      duration.

PMID- 16612674
TI  - The WHO-ILAR COPCORD Bhigwan (India) model: foundation for a future COPCORD
      design and data repository.
AB  - Launched by the International League of Associations for Rheumatology (ILAR) and
      the World Health Organization (WHO), the Community oriented program for control
      of rheumatic diseases (COPCORD) aims to fill the gaps in the knowledge on the
      global burden of rheumatic musculoskeletal disorders (RMS). During the population
      survey (Stage I), data on symptoms (pain and disability in focus), rather than
      diseases or syndromes, is collected. The survey may be followed by a planned
      stage to impart health education, identify risk factors, and devise preventive
      and control strategies. Several countries in the Asia Pacific and Pan-America
      have completed COPCORD survey. Africa has recently joined. Only COPCORD Bhigwan
      (India) has continued into the tenth year. COPCORD Bhigwan is a fast-track model
      that has provided significant data on rheumatic disorders. Using COPCORD Bhigwan
      model, the Bone and Joint Decade (BJD) India has launched several population
      surveys to measure the RMS burden. There is an urgent need for a COPCORD data
      repository. Several COPCORD have differed in their methods. Differences pertain
      to population sample size, techniques for data collection and recording,
      chronology of events and phases, and classification of
      symptoms/diseases/disorders. The COPCORD model in current global use needs to be
      revised. Based on the COPCORD Bhigwan model, a future design for COPCORD is
      proposed. COPCORD needs to have a uniform and standardized core program with a
      flexibility to cater to regional needs. It must imbibe some of the recent
      advances in rheumatology while retaining its socioeconomic appeal. It must have a
      planned follow-up/longitudinal observational phase. Above all, it must serve and
      benefit community. WHO-ILAR COPCORD and the global BJD initiative must join hands
      to serve a common cause of controlling rheumatic musculoskeletal disorders.
      COPCORD is also a reflection of the ILAR mission statement "think global, act
      local."

PMID- 16612699
TI  - Are there second thoughts about the results of the WHI study?
AB  - The publication of the Women's Health Initiative (WHI) study had significant
      impact on the attitude of physicians and patients towards the use of hormones in
      the menopause. It has been estimated that 40-83% of patients using hormones
      ceased treatment on their own initiative following publication of the WHI
      results. While in the pre-WHI period, use of hormones in the menopause was termed
      'hormone-replacement therapy' (HRT) with an emphasis on replacement; 'HRT' has
      now been replaced with the term 'hormone therapy' (HT), focusing on the therapy's
      status as a treatment with defined risks and benefits. Following the publication
      of the WHI study, many caregivers concluded that HT had absolutely no role in
      clinical practice. However, the decision to begin HT for the symptomatic,
      healthy, newly postmenopausal woman should be based on whether the WHI study
      addresses all the issues that must be taken into consideration before initiation
      of HT, whether there are effective alternatives available to relieve climacteric
      symptoms, and also whether HT is better able to prevent cardiovascular disease
      (CVD) and Alzheimer's disease (AD) than to halt atherosclerotic lesions. Every
      postmenopausal woman should have an individual risk-benefit evaluation to
      determine whether HT suits her needs. Until the effectiveness of HT for primary
      prevention of CVD and AD is established or disproved, there is no justification
      for HT use in the asymptomatic postmenopausal woman. However, symptomatic newly
      menopausal women might experience relief of their climacteric symptoms following
      HT use without exposing themselves to unreasonable risks.

PMID- 16612700
TI  - The comparison of vessels in elective and spontaneous abortion decidua in first
      trimester pregnancies: importance of vascular changes in early pregnancy losses.
AB  - BACKGROUND: To determine whether adequate trophoblastic migration and maternal
      placental perfusion occurs in cases of early pregnancy loss, we compared vessels
      in elective abortion decidua with those in spontaneous abortion decidua. METHODS:
      Elective abortion decidua at 5-11 weeks (n = 40) were compared with spontaneous
      abortion decidua at 5-12 weeks (n = 25). Also normal late secretory endometrial
      biopsy specimens (n = 10) were examined. The cross-sections of veins and arteries
      were counted in 25 elective and 15 spontaneous abortion materials. The number of
      the veins that contain trophoblastic fragments and the number of the spiral
      arteries converted by trophoblasts were determined. Statistical significance by
      Mann-Whitney U and Spearman's correlation test was p < 0.05. RESULTS: All sets of
      decidua had dilated veins, but no secretory endometrium did. The ratio of
      converted spiral arteries to nonconverted arteries was much more in elective
      abortion decidua (113/938, 12.04%) than in spontaneous abortion decidua (11/511,
      2.15%) (p < 0.001). CONCLUSIONS: The presence of converted arteries, dilated
      veins, and intravenous trophoblastic fragments in decidual specimens were
      evidence of intervillous circulation and placental perfusion by maternal
      circulation in the first trimester. Also the insufficient conversion of the
      arteries in spontaneous abortions might be responsible for many cases of early
      pregnancy loss.

PMID- 16612701
TI  - Symphysis-fundus measurements for detection of small for gestational age
      pregnancies.
AB  - BACKGROUND: In Sweden measurements of the symphysis-fundus (SF) distance are used
      to detect small for gestational age (SGA) pregnancies. The aim of this study was
      to evaluate the efficiency of Swedish ultrasound-based SF reference curves in
      detecting SGA pregnancies. METHODS: To assess the sensitivity for detection of
      SGA pregnancies we performed a case-control study. Through the Swedish Medical
      Birth Register we identified all singleton SGA infants born in Uppsala in 1993
      1997 and randomly recruited non-SGA singleton infants as controls. We included
      169 term and 73 preterm SGA cases and 296 controls, all born at term. The
      reference curves constructed by Steingrimsdottir (S curve) and Kieler (K curve)
      were evaluated. Gestational age at the first alarm in the preterm SGA group was
      recorded. RESULTS: In term pregnancies the S curve showed a sensitivity of 32%
      and specificity of 90% at a cut-off of -2 SDs. The corresponding values for the K
      curve were 51% and 83%, respectively. In preterm SGA pregnancies the sensitivity
      of the S curve was 49% and of the K curve 58%. The first alarm below 2 SDs was
      noted before 32 weeks in 37% with the S curve and 43% with the K curve for
      preterm SGA pregnancies. CONCLUSIONS: Both tested Swedish SF reference curves had
      low sensitivities for term SGA pregnancies. Sensitivity was higher for the
      preterm group and SF measurements seem to be better for detecting the most severe
      cases of SGA.

PMID- 16612702
TI  - Association of maternal protein intake before conception and throughout pregnancy
      with birth weight.
AB  - BACKGROUND: The aim of this study is to analyze how the maternal intake of
      macronutrients before conception and in the 6th, 10th, 26th, and 38th weeks of
      pregnancy affects birth weight. METHODS: A longitudinal study of food consumption
      to assess the nutritional status of 77 healthy female volunteers (age range: 24
      36) who were planning immediate pregnancy was performed in Reus between 1992 and
      1996. A seven-consecutive-day dietary record was used in order to evaluate the
      dietary intake. We fitted multiple linear regression models of macronutrients on
      birth weight adjusted for energy intake, maternal age, pre-conceptional body mass
      index, sex of the newborn, length of pregnancy, parity, physical activity in
      leisure time, and smoking. RESULTS: In the 6th, 10th, and 26th weeks of
      pregnancy, 7.2-12.7% of the variability of the birth weight can be explained by
      the intake of macronutrients. In the protein and fat model, a 1 g increase in
      maternal protein intake during preconception and in the 10th, 26th, and 38th
      weeks of pregnancy leads to a significant increase of 7.8-11.4 g in birth weight.
      CONCLUSIONS: The diet of well-nourished women in the preconception period and
      throughout most of pregnancy has a significant effect on birth weight, and
      proteins are the macronutrient that has the greatest influence.

PMID- 16612703
TI  - Intrapartum transfer from a birth centre to a hospital - reasons, procedures, and
      consequences.
AB  - BACKGROUND: Investigation of the reasons for the transfer of women from a birth
      centre to a hospital in the course of childbirth as well as modalities and
      effects. PATIENTS AND METHOD: In the prospective investigation from September 1,
      1999 to August 31, 2001, information was collected for all women in Berlin and
      Bavaria transferred intrapartum from a birth centre to a hospital concerning the
      reason for the transfer, stage of delivery at the start of transfer, details of
      the transport, accompaniment, state of mother and medical diagnosis on arrival at
      the hospital, further progress of delivery, and the condition of the baby
      postnatum. Comparison groups were formed by all birth centre deliveries in Berlin
      and Bavaria 1999/2000 (n = 3060) and hospital deliveries in Berlin and Bavaria
      1998/1999 (selected data, n = 89 696 births). RESULTS: Three hundred and sixty
      transfer cases could be evaluated, and a majority of these were nulliparous. The
      most frequent reasons for transfer were prior premature rupture of membranes and
      failure to progress in labor. Fifty-seven percentages of the women who were
      transferred subsequently delivered spontaneously, with an episiotomy rate of
      approximately 30%. 1-min Apgar value < or = 7 were frequently in nulliparous and
      multiparous patients in the transfer group than in the comparison groups, as were
      5-min Apgar values < or = 7 and pH < 7.10 in arterial cord blood in particular
      for nulliparous in the transfer group. Hospitalisation of neonates born to the
      transfer group and in particular the nulliparous was significantly more common.
      CONCLUSIONS: Women delivering in a birth centre represent in general a low-risk
      group as a result of careful preselection by the centres. However, some neonatal
      data and the high rate of operative deliveries (cesarean section, forceps, and
      vaginal extraction) indicate that the intrapartum-transferred women, in
      particular when nulliparous, represent than a special high-risk group.

PMID- 16612704
TI  - Methods for myometrium closure and other factors impacting effects on cesarean
      section scars of the uterine segment detected by the ultrasonography.
AB  - OBJECTIVE: Ultrasound examination is an objective method for assessment of
      uterine scar defects. The present study was conducted to compare single-layer
      interrupted sutures (Group A) with double-layer interrupted sutures (Group B) and
      our new method (Group C) as well as other perioperative parameters in relation to
      risk of wedge defects in scars. METHODS: We have introduced a new myometrium
      closure procedure consisting of continuous suture with decidual closure followed
      by interrupted myometrium suture. In this prospective study, women undergoing
      cesarean operation (n = 137) were examined by transvaginal ultrasound one month
      after surgery to assess the appearance of lower uterine scars. Multivariate
      logistic regression analysis was performed to identify associations of
      perioperative parameters and methods for lower myometrium closure with abnormal
      wedge formation. RESULTS: Wedge defects were observed in a total of 27 patients
      (19.7%). The analysis revealed Groups B and C to have reduced risks with odds
      ratios of 0.28 and 0.077, respectively, as compared to Group A. Furthermore,
      increasing gestational week at delivery, plural fetal pregnancies, premature
      rupture of membranes and pre-eclampsia were also linked with an increased risk,
      with odds ratios of 1.4-8.9. CONCLUSION: The incidence of uterine scar defects 1
      month after cesarean sections varies with the method applied for myometrial
      suture and perioperative variables. The data suggest that methods for myometrium
      closure as well as other factors influence the condition of myometrial healing.

PMID- 16612705
TI  - Fear of childbirth and history of abuse: implications for pregnancy and delivery.
AB  - BACKGROUND: The aim of this study was to assess the prevalence of fear of
      childbirth, and to find possible associations to selected sociodemographic
      factors and important life events. A secondary aim was to explore the
      relationship between these factors and pregnancy outcome. METHODS: Questionnaire
      booklets were sent to 2680 women at 18 weeks of gestation, of whom 1452 women
      (54%) responded. The questionnaire included background factors (marital status,
      education, history of abuse, current pregnancy), W-DEQ (measurement of fear of
      childbirth), and STAI (measurement of subjective anxiety). Pregnancy outcome
      information was recorded. RESULTS: The prevalence of serious fear of childbirth
      (W-DEQ > 100) was 5.5%. The W-DEQ and STAI scores were positively correlated (r =
      0.44, p < 0.001). Among the anxious women, a trend towards more frequent
      operative vaginal delivery (12.1% versus 6.9%, p = 0.07) was noted, but not for
      emergency cesarean section (10.6% versus 7.6%, p = 0.34). Women who reported
      being exposed to physical or sexual abuse in childhood had a higher W-DEQ score
      (71, SD 31 and 69, SD 27) than did the non-abused (61, SD 23, p < 0.01). Only
      half of women sexually or physically abused in childhood (54% and 57%
      respectively) had uncomplicated vaginal delivery at term versus 75% among non
      abused (p < 0.001). CONCLUSION: The prevalence of serious fear of childbirth was
      5.5%. Fear of childbirth was not associated with mode of delivery, whereas sexual
      or physical abuse in childhood influenced negatively mode of delivery.

PMID- 16612706
TI  - Performance of acupuncture as labor analgesia in the clinical setting.
AB  - BACKGROUND: Three randomized controlled trials have shown that acupuncture during
      labor can reduce the use of epidural analgesia and meperidine. To supplement
      these trials, we have designed an observational study to answer the research
      question: "Do laboring women in a normal hospital setting who receive acupuncture
      require less epidural analgesia than those who do not receive acupuncture?"
      METHODS:  SETTING: Delivery ward of a tertiary care University hospital in
      Norway. SUBJECTS: All attempted vaginal labors during the period 01.12.99
      31.12.03 (n = 17,741). STATISTICAL ANALYSIS: Multivariate logistic regression
      analysis. RESULTS: The dependent variable in the regression analysis was use of
      epidural analgesia. The independent variables were: use of acupuncture, use of
      nitrous oxide, use of meperidine, parity, ethnicity, age, duration of pregnancy,
      type of labor (induced or not), and duration of first stage of labor. In the
      multivariate analysis the odds ratio for having an epidural was 0.6 (95% CI 0.5
      0.7) for the patients having acupuncture compared to those not having
      acupuncture. CONCLUSIONS: Women having acupuncture as labor analgesia in the
      clinical setting have a reduced use of epidural analgesia.

PMID- 16612707
TI  - Performance of Pap smear and human papilloma virus testing in the follow-up of
      women with cervical intraepithelial neoplasia grade 1 managed conservatively.
AB  - BACKGROUND: Conservative management (follow-up) of cervical intraepithelial
      neoplasia grade 1 (CIN1) is acceptable, but evidence on performance of follow-up
      tools, such as Pap smear and human papilloma virus (HPV) test, is still needed.
      METHODS: A cohort of 78 women with histologically confirmed CIN1, referred
      because of atypical squamous cell or low-grade squamous intraepithelial lesion in
      their Pap smear, was enrolled between August 2000 and September 2002 and was
      prospectively followed-up at 6 and 12 months, until September 2003. Follow-up
      examinations included Pap test and Hybrid Capture II (HCII) with high-risk HPV,
      colposcopy, and cervical biopsies in patients with persistent abnormalities. Odds
      ratios and performance indicators (with 95% confidence interval) were calculated
      for HPV and Pap test results in detecting biopsy-confirmed CIN during the follow
      up. RESULTS: Thirty-seven (47%) of the women were HPV-positive at baseline. At
      first follow-up visit, 30 women had persistent CIN1 and one woman progressed to
      CIN2; 15 patients had CIN1 and one patient CIN2 at the second follow-up visit.
      Women with persistent CIN1 (or progression) during follow-up had a significantly
      higher HPV detection rate and abnormal Pap tests, compared to women with
      regressive disease. Cytology had a far better sensitivity in detecting CIN than
      HCII at the first follow-up visit (81 versus 52%, respectively), whereas both
      examinations had equivalent sensitivities at the second follow-up visit (69 and
      56%, respectively). Cytology had a superior negative predictive value at the
      first follow-up visit and better positive predictive value, in addition, at the
      second visit. CONCLUSIONS: Because cytological abnormalities correlated generally
      better with the persistence of biopsy-confirmed CIN1 in this follow-up protocol,
      HCII test is the second-hand option to Pap test, but the use of both Pap and HCII
      together seems an unnecessary waste of resources.

PMID- 16612708
TI  - Validation of a test model of induced dysmenorrhea.
AB  - BACKGROUND: The myometrial hyperactivity and reduced uterine blood flow of
      primary dysmenorrhea is to a large extent caused by increased vasopressin
      secretion. A new therapeutic approach for this condition is to develop
      antagonists of uterine vasopressin V1a receptors. We studied a test model of
      vasopressin-induced dysmenorrhea in healthy, sterilized women and compared
      responses against those in dysmenorrheic subjects. METHODS: Eight women with
      primary dysmenorrhea and eight sterilized, healthy women participated in
      recordings of intrauterine pressure and experienced pain on days 1-2 of two
      menstruations. We tried to identify biochemical markers in plasma of uterine
      ischemia. Furthermore, the effects of repeated bolus injections of 10 pmol/kg b w
      of vasopressin or placebo on these parameters were assessed. RESULTS: The
      vasopressin injections caused statistically significant increases in the area
      under the intrauterine pressure curve (AUC) in both healthy volunteers and
      patients with dysmenorrhea, the overall responses being greater in healthy
      volunteers. The experienced pain measured by visual analog scale in individual
      dysmenorrheic subjects tended to show higher maximal post-dose scores for the
      vasopressin injections than for placebo. Maximum visual analog scale scores and
      maximum AUCs in individual subjects tended to be related. Mean creatine kinase MB
      levels were higher in women with dysmenorrhea than in healthy subjects both
      before and after vasopressin administration, the converse being observed for C
      reactive protein levels. CONCLUSIONS: The present model appears to be useful for
      evaluating new drugs for the treatment of primary dysmenorrhea.

PMID- 16612709
TI  - Peritoneal fluid and serum levels of hepatocyte growth factor may predict the
      activity of endometriosis.
AB  - BACKGROUND: The suitable parameter in PF as well as in serum that may predict the
      activity of endometriosis is not well described. Therefore, we tried to examine
      the peritoneal fluid (PF) and serum concentrations of hepatocyte growth factor
      (HGF) in different revised American Society of Reproductive Medicine (r-ASRM)
      staging and morphologic appearances of endometriosis in an attempt to determine
      whether HGF can be clinically useful to predict the activity of pelvic
      endometriosis. METHODS: Peritoneal fluid was collected from 137 women with
      endometriosis and 57 women without endometriosis during laparoscopy and blood
      sampling was collected from 37 women with endometriosis and 21 women without
      endometriosis before laparoscopy. The concentration of HGF in PF and serum was
      measured by enzyme-linked immunosorbent assay. The ability of isolated
      macrophages and stroma to secrete HGF in response to lipopolysaccharide (LPS) was
      evaluated. RESULTS: A significantly increased concentration of HGF in PF was
      found in women with endometriosis (1451.75 +/- 90.7 pg/mL) than that in non
      endometriosis (1120.5 +/- 77.3 pg/mL, p < 0.01) without any remarkable difference
      in HGF levels between women with stage I-/II endometriosis and stage III-/IV
      endometriosis. When we distributed serum and PF levels of HGF according to
      different color appearances of endometriosis, we found a significantly higher
      serum and PF levels of HGF in women containing dominant red peritoneal lesions in
      pelvic cavity (740 +/- 109.3 pg/mL for serum; 1685 +/- 183.4 pg/mL for PF) than
      those having other pigmented lesions (649 +/- 79.5 pg/mL, p < 0.05 for serum;
      1224 +/- 67.8 pg/mL, p < 0.05 for PF) or chocolate cysts (485 +/- 43.1 pg/mL, p <
      0.05 for serum; 1118 +/- 83.1 pg/mL, p < 0.01 for PF). Exogenous stimulation with
      LPS significantly increased the production of HGF in the culture media by
      macrophages and stroma derived from women with endometriosis than that in women
      without endometriosis. CONCLUSIONS: These results suggest that women with early
      or advanced endometriosis as measured by r-ASRM scoring system are not associated
      with an increase in either serum or PF concentrations of HGF. Rather HGF levels
      in serum and PF were significantly increased in women harboring blood-filled red
      peritoneal lesions and may be clinically useful to predict the activity of pelvic
      endometriosis.

PMID- 16612710
TI  - Spontaneous abortion: a prospective cohort study of younger women from the
      general population in Denmark. Validation, occurrence and risk determinants.
AB  - OBJECTIVE: To assess the occurrence of spontaneous abortion, comparing two
      different data sources. To estimate the rate of spontaneous abortion over a 2
      year period, and examine potential predictors of the risk for incident
      spontaneous abortion. METHODS: We used interview data from a population-based
      prospective cohort study comprising 11,088 women and data from a linkage of the
      cohort with the Hospital Discharge Register to compare spontaneous abortions as
      reported in the interview with those identified in the register. Based on
      interview data, we estimated the rate of spontaneous abortion during the two-year
      follow-up. Finally, risk determinants for incident spontaneous abortion were
      analyzed by means of logistic regression. RESULTS: A total of 654 spontaneous
      abortions before enrolment in the study were reported by the women compared to
      531 abortions found in the register. More than 80% of the spontaneous abortions
      identified from both sources were recorded in the same year. During follow-up a
      total of 20.9% of pregnancies intended to be carried to term ended as a
      spontaneous abortion. In the risk factor analysis, we found that previous
      spontaneous abortion, being single, never having used oral contraceptives, and
      use of intrauterine device were associated with increased risk of subsequent
      spontaneous abortion. In addition, it was indicated that a short interpregnancy
      interval following a spontaneous abortion may confer an increased risk of
      abortion in the subsequent pregnancy. CONCLUSION: We found a high rate of
      spontaneous abortion in the present study and an acceptable agreement between
      information obtained by interview and register information. More than 25% of the
      spontaneous abortions were only reported by the women, and this could not be
      explained by erroneously reported induced abortions, and may be early,
      nonhospitalized abortions. We confirm that number of previous spontaneous
      abortions is a strong determinant, and our data may also indicate a role of
      previous contraceptive habits. A role of the length of interpregnancy interval in
      the risk of spontaneous abortion cannot be ruled out.

PMID- 16612711
TI  - Postoperative voiding, bacteriuria and urinary tract infection with Foley
      catheterization after gynecological surgery.
AB  - BACKGROUND: The use of bladder drainage to avoid urinary retention after
      gynecological surgery is more or less custom based, and duration of drainage
      varies considerably. In this paper the use of 1-day drainage by transurethral
      Foley catheter was investigated with regard to impaired voiding, asymptomatic
      bacteriuria, and urinary tract infection. Furthermore, the use of methenamine
      hippurate was studied with regard to postoperative asymptomatic bacteriuria and
      urinary tract infection. METHODS. This summary is based on six published papers
      totaling 917 patients. In three case series, 1-day catheterization was used in
      women undergoing gynecological laparotomy, colposuspension, or vaginal plastic
      surgery. To compare 1- and 3-day Foley catheterization, two open, randomized
      trials were performed on women undergoing vaginal plastic surgery or
      colposuspension. The last study was a double-blind trial between methenamine
      hippurate and placebo as prophylaxis against urinary tract infection and
      asymptomatic bacteriuria using 1-day catheterization. RESULTS: Postoperative
      voiding problems and urinary tract infection occurred infrequently with 1-day
      catheterization, and no more frequently than with catheterization for three days.
      Methenamine hippurate decreased the incidence of urinary tract infection and
      asymptomatic bacteriuria by 80 and 40%, respectively. CONCLUSIONS: One-day
      bladder drainage by transurethral Foley catheter may be used routinely in common
      gynecological surgery with a low rate of voiding problems, asymptomatic
      bacteriuria, and urinary tract infection. Methenamine hippurate prophylaxis
      effectively reduces postoperative urinary tract infection.

PMID- 16612712
TI  - Long-term results of the tension-free vaginal tape operation in an unselected
      group of 129 stress incontinent women.
AB  - BACKGROUND: This study was undertaken to examine the long-term effects and
      effectiveness of the tension-free vaginal tape (TVT) procedure in an unselected
      group of women. METHOD: One hundred and twenty-nine stress urinary incontinent
      women (including primary, recurrent, mixed, and low pressure urethra cases) were
      studied prospectively and examined according to a strict protocol at a mean time
      of 6 years after their TVT operation. Cough and pad tests were used for objective
      evaluation, whereas visual analog scale and patients' verbal estimation were
      applied for subjective evaluation. RESULTS: As assessed by the cough stress test
      and the pad test, 74 and 81% of the women were totally cured, respectively.
      Symptoms possibly indicating reduced urine flow were reported from 17% of the
      women and recurrent urinary tract infections from 9.3% of the women. The de novo
      urge rate was 4.7%. The tape was visualized in 3.1% of the women and necessitated
      resection in 1.6% of the cases due to subjective discomfort. No serious or
      unexpected adverse events were revealed. CONCLUSION: The TVT operation appears to
      be a safe and effective anti-incontinence procedure in all female stress
      incontinence subgroups.

PMID- 16612713
TI  - The effect of accelerated rehabilitation on recovery after surgery for ovarian
      malignancy.
AB  - BACKGROUND: In patients undergoing colonic surgery the postoperative hospital
      stay has been reduced from 8-12 days to 2-4 days with multimodal rehabilitation
      programs. The aim of this study was to evaluate the postoperative outcome after
      surgery for ovarian malignancy with conventional care compared to fast-track
      multimodal rehabilitation. METHODS: Seventy-two consecutive patients receiving
      conventional care (group 1) were compared with 69 consecutive patients receiving
      multimodal, fast-track rehabilitation with a planned care program including
      continuous epidural analgesia, early oral feeding and mobilization (group 2) in
      the same department. Outcome was postoperative hospital stay and morbidity during
      the first postoperative month. RESULTS: Median age was 63 years (group 1) and 62
      years (group 2). Median postoperative hospital stay was reduced from 6 days in
      group 1 (mean 7.3) to 5 days in group 2 (mean 5.4) (p < 0.05). There was no
      difference in the overall complication rate, although severe medical
      complications were reduced in group 2 (14% versus 2%; p < 0.01). Readmission rate
      was 10% in group 1 and 3% in group 2 (p > 0.05). CONCLUSIONS: The concept of fast
      track multimodal rehabilitation appears to be beneficial in patients operated for
      ovarian malignancy, as hospital stay and medical morbidity are reduced.

PMID- 16612714
TI  - COX-2 and preoperative CA-125 level are strongly correlated with survival and
      clinical responsiveness to chemotherapy in ovarian cancer.
AB  - BACKGROUND: CA-125 is elevated in the serum of the majority of ovarian carcinoma
      patients. Cyclooxygenase-2 is an enzyme whose synthesis is upgraded by several
      cytokines, growth factors, and tumor promoters. METHODS: We analyzed
      cyclooxygenase-2, preoperative CA-125 levels, and CA-125 levels during
      chemotherapy in 41 FIGO stage III, grade 3, ovarian serous carcinoma patients in
      relation to survival with a logistic regression. The correlation of
      cyclooxygenase-2 expression and CA-125 preoperative level with clinical
      responsiveness to chemotherapy was studied according to Fisher's exact test. We
      compared 23 patients living with no evident disease five years after primary
      treatment to 18 patients who had died of progression of disease no later than two
      years after primary treatment. RESULTS: Cyclooxygenase-2 overexpression (p =
      0.014 and p = 0.036) and preoperative CA-125 level (p = 0.012 and p = 0.029) were
      found to be independent predictors of survival in univariate and multivariate
      analyses. Cyclooxygenase-2 and CA-125 level were correlated to responsiveness to
      chemotherapy (p = 0.003 and p = 0.036, respectively; Fisher's exact test). The
      patients with a CA-125 level <35 U/ml after two cycles of chemotherapy showed a
      longer survival (p = 0.008). The median preoperative CA-125 was 195 in high
      survival patients and 650 in low survival patients (p= 0.004, Wilcoxon Mann
      Whitney test). CONCLUSIONS: Cyclooxygenase-2 overexpression and CA-125 levels may
      help the management of ovarian cancer patients, permitting the selection of more
      aggressive and tailored first-line therapy.

PMID- 16612715
TI  - Maternal mortality audit in a hospital in Northern Namibia: the impact of
      HIV/AIDS.

PMID- 16612716
TI  - Successful pregnancy in a patient with initially procidentia uteri.

PMID- 16612717
TI  - Severe reversible myocardial depression in septic abortion.

PMID- 16612718
TI  - Postablation-tubal sterilization syndrome following thermal balloon endometrial
      ablation.

PMID- 16612719
TI  - Primary malignant mixed Mullerian tumor arising in the rectosigmoid.

PMID- 16612720
TI  - Diagnostic accuracy of three-dimensional hysterosalpingo-contrast-sonography.

PMID- 16612722
TI  - Therapeutic use of ultrasound targeted microbubble destruction: a review of non
      cardiac applications.
AB  - The development of second generation ultrasound contrast agents has extended the
      diagnostic scope of ultrasound imaging. Due to their physical characteristics, a
      therapeutic application of such microbubble based contrast agents has been
      promoted. Recently, several groups have demonstrated that ultrasound targeted
      microbubble destruction (UTMD) may deliver drugs or gene therapy vectors to
      organs accessible by ultrasound, thus providing a new technique for non-invasive,
      organ specific delivery of bioactive substances. Most applications in this field
      have been tested in cardiac models, but other organs can be treated as well. This
      article will give an overview of the background of UTMD and its non-cardiac
      applications.

PMID- 16612723
TI  - Duplex sonography after living donor kidney transplantation: new insights in the
      early postoperative phase.
AB  - AIM: Vascular complications of kidney transplantation, including transplant vein
      thrombosis, are relevant causes for graft loss in the early postoperative phase.
      However, duplex flow characteristics after living renal transplantation are
      widely unknown. Aim of the study was to assess renal perfusion in the
      postoperative period with special emphasis on the renal vein. METHODS: 22
      consecutive kidney graft recipients and their donors were included and
      prospectively followed up for three months. The following Doppler parameters were
      collected: in the donor before operation: the intrarenal resistive index (RI), in
      the recipient after transplantation and at one and three months: the intrarenal
      RI, peak flow velocities and area under the curve in the renal vein, as well as
      peak systolic velocities of the iliac and renal artery. RESULTS: None of the 22
      transplants failed due to vascular complications. Highest median venous (92 cm/s
      [range 22-211]) and arterial peak velocities (271.5 cm/s [141.5-458]) were
      observed close to the anastomosis immediately after transplantation. During
      follow-up, flow parameters significantly decreased at three months (44.3 cm/s
      [13.3-156.9] and 186.8 cm/s [105.5-267.5]). The RI decreased from donor to
      recipient at the day of operation due to tachycardia (0.65 to 0.60; P = 0.06).
      After correction for heart rate, the RI was stable during follow-up. CONCLUSIONS:
      Initial high peak velocities in conjunction with stable resistive indices in a
      cohort, free of vascular graft complications, suggest a postoperative physiologic
      adaptation process rather than a relevant stenosis requiring medical
      intervention.

PMID- 16612724
TI  - Comparison of the acoustic streaming in amniotic fluid and water in medical
      ultrasonic beams.
AB  - AIM: Acoustic streaming in amniotic fluid has been investigated under a variety
      of conditions relevant to the diagnostic use of ultrasound. METHOD: An ultrasonic
      Doppler method has been used for measurement. Streaming velocities have been
      compared with those generated in water for the same exposure conditions. Beams
      were generated by laboratory equipment simulating beams from clinical systems.
      The fluids were insonated IN VITRO using 3.5 MHz, 5 MHz and 7.5 MHz transducers
      in continuous wave (CW) and pulsed mode. RESULTS: Acoustic streaming was measured
      in both amniotic fluid and water at the power levels 50 mW and 140 mW.
      Enhancement of velocities due to non-linear effects in high amplitude pulses was
      demonstrated for amniotic fluid as well as for water. The potential and
      limitations of present numeric methods for the prediction of acoustic streaming
      were explored. CONCLUSION: Pulsed ultrasound caused similar streaming velocities
      in amniotic fluid and water while continuous wave beams induced significantly
      faster streaming in amniotic fluid than in water.

PMID- 16612725
TI  - [Trans-fontanellar Doppler sonography of the intracranial veins in infants. Part
      II--pathology].
AB  - Colour coded Doppler sonography can be very helpful for the diagnosis of
      haemorrhagic infarction of the brain parenchyma, cerebral venous thrombosis and
      arterio-venous malformations of the brain. Intracranial haemorrhages into the
      brain parenchyma are caused by the compression of the subependymal and terminal
      veins which impede the venous drainage from the white matter. Haemorrhage of the
      basal ganglia is highly suspicious of cerebral venous thrombosis especially of
      the deep venous drainage. Unilateral occlusion of only one internal cerebral vein
      causes unilateral haemorrhage, bilateral thrombosis of both internal cerebral
      veins as well as occlusion of the great vein of Galens or the straight sinus
      causes bilateral haemorrhage of the basal ganglia as well as ventricular
      haemorrhage and haemorrhagic infarction of the white matter. The most common
      arterio-venous malformation of the brain is AV-malformation of Galens's vein.
      Sonographically, a pulsating cystic structure behind the 3rd ventricle can be
      shown. Colour coded Doppler sonography demonstrates the vascular nature of the
      cyst. Doppler sonography can show the feeding arteries, most frequently the
      posterior choroidal arteries and the venous drainage by the straight sinus.

PMID- 16612726
TI  - [Early systolic notched peripheral Doppler flow pattern as an indicator of
      functional obstruction of the common iliac artery after iatrogenic aortic
      dissection: a case report].
AB  - We report on a 57-year-old male patient with typical claudication localised in
      the right thigh, following aortic valve replacement. The ankle brachial index
      under resting conditions is within normal range on both sides. A conspicuous
      monomorphic double-humped peripheral Doppler flow pattern with an early systolic
      notch extending to the baseline can be registered in all the arteries of the
      right lower limb. The flow patterns of all other peripheral arteries are properly
      configured and of triphasic morphology. As the underlying cause of the
      pathologically altered Doppler flow morphology, aortic dissection Type A can be
      detected, extending from the former cannulation site of the ascending aorta into
      the right common iliac artery. Its dissection membrane functionally occludes the
      right common iliac artery in the early systole, the effect being brief and
      reversible. The pathogenesis of this morphologically altered Doppler flow pattern
      and potential differential diagnoses are discussed in this case report, also
      considering the current literature.

PMID- 16612727
TI  - Focal myositis of the iliopsoas muscle--a benign pseudotumour: ultrasound
      appearance in correlation with CT and MRI.
AB  - OBJECTIVE: Focal myositis of the iliopsoas muscle is a rare condition. A case is
      presented, emphasizing the value of ultrasound for detection, localisation, image
      guided biopsy and follow-up in correlation with CT and MRI findings. MATERIAL AND
      METHODS: A 58-year-old woman was referred to our clinic with strong left sided
      inguinal pain, which radiated to the thigh and had lasted for four days.
      Ultrasound, CT and MRI were performed. Ultrasound-guided biopsy with histological
      correlation was obtained and US-follow-ups were available. RESULTS: CT showed an
      enlarged iliopsoas muscle on the left side without any focal pathology or
      enhancement. MRI revealed a sharpely delineated lesion, which was hypointense to
      muscle in fat-suppressed T1 w images with circumferential enhancement and showed
      a hyperintense appearance in T2 w images. Ultrasound displayed a polylobulated,
      inhomogeneous and hypoechoic tumour within the iliopsoas muscle. Ultrasound
      guided biopsy was found to be compatible with myositis. After oral therapy with
      steroids, improvement could be documented by serial ultrasound follow-up as the
      size of the tumour was definitely regressing. CONCLUSION: Focal myositis of the
      iliopsoas muscle is a rare entity which may mimic a tumoural lesion. Imaging
      findings may not be conclusive, and US-guided biopsy is recommended to rule out a
      malignant mass. Ultrasound seems to be the most cost-effective method for
      diagnosis, image guided biopsy and follow-up.

PMID- 16612728
TI  - [DEGUM grade I quality standards in obstetric ultrasound diagnosis during the
      19th-22nd week of pregnancy].

PMID- 16612729
TI  - [Hydration for the prevention of contrast medium-induced nephropathy: an update].
AB  - Contrast medium-induced nephropathy (CIN) continues to be one of the most common
      causes of hospital-acquired acute renal failure. Since most of the clinical
      studies on the prophylactic use of different drugs to prevent CIN produced
      disappointing results, hydration remains the mainstay of prophylaxis. A number of
      recent prospective randomized trials provided further evidence of the
      effectiveness of hydration and relevant information regarding the optimization of
      hydration protocols. It was shown that a bolus hydration solely during
      examination is not sufficient to prevent CIN. In addition, isotonic 0.9 % saline
      was superior to the commonly used half-isotonic 0.45 % saline in another trial.
      An outpatient hydration protocol including oral hydration before the examination
      followed by forced intravenous hydration over 6 hrs. beginning 30 to 60 min.
      prior to examination seems to be comparable to the usual hydration over 24 hrs.
      Another hydration protocol, which could also be very attractive especially for
      outpatients, included the infusion of sodium bicarbonate. In a recent trial,
      hydration with sodium bicarbonate, given as a bolus for 1 hr. prior to
      examination followed by an infusion for 6 hrs. after examination, was more
      effective than hydration with sodium chloride for the prophylaxis of CIN.
      However, there is still a lack of large-scale, multi-center trials comparing
      different hydration protocols and investigating their influence on clinically
      relevant endpoints such as mortality or the need for dialysis.

PMID- 16612730
TI  - [Preoperative and palliative embolization of renal cell carcinomas: follow-up of
      49 patients].
AB  - PURPOSE: To evaluate the influence of preoperative and palliative embolization of
      renal cell carcinomas on survival, intra- and post-operative procedures, and
      symptom control for palliative and preoperative indications. MATERIALS AND
      METHODS: 56 patients who underwent renal cell carcinoma embolization from 1981 to
      1999 were included in this retrospective study. RESULTS: 24 women and 32 men were
      included (mean age 59.4 years). Complete follow-up data was available for 49
      patients. 42 patients underwent preoperative embolization at different tumor
      stages (pT1: 1 patient, pT2: 6, pT3 a: 4, pT3 b: 19, pT3 c: 2, pT4: 5). 14
      patients underwent palliative embolization (T1: 0 patients, T2: 5, T3: 4, T4: 4).
      Indications for preoperative embolization were bleeding of the renal tumor in 6
      cases -- non-recurrent bleeding reported, flank pain in 4 patients -- 3 of 4
      patients had no further symptoms, recurrent tumor embolization in 1 patient, and
      2 patients who wanted to be treated without symptoms. The mean survival time of
      preoperative embolized patients was 3.1 +/- 5.11 years with a 5-year survival
      rate of 50 %. The mean survival time of palliative embolized patients was 0.67 +/
      0.76 years with initial metastases (n = 7) and 2.33 +/- 2.40 without metastases
      (n = 6). CONCLUSION: Palliative embolization of renal cell carcinomas is a safe
      therapeutic method to treat advanced renal cell carcinomas allowing control of
      symptoms such as hematuria and flank pain in more than 90 % of our cases.
      Preoperative embolization yields a patient survival time comparable to that of
      patients at earlier tumor stages and is dependent on the metastases.

PMID- 16612731
TI  - [Value of diffusion-weighted imaging for diagnosing vertebral metastases due to
      prostate cancer in comparison to other primary tumors].
AB  - PURPOSE: Several publications have reported that the apparent diffusion
      coefficient is generally lower in metastatically affected vertebrae. Therefore,
      metastases are represented in diffusion-weighted images by increased signal
      intensity in comparison to unaffected vertebrae. However, there were indications
      that metastases due to prostate cancer may differ from this. Therefore, the
      contrast behavior of vertebral metastases due to prostate cancer or tumors with
      another histology are to be systematically studied using diffusion-weighted
      images. The present study is intended to examine whether the two groups differed
      and whether possible differences depended on the degree of sclerosis. MATERIALS
      AND METHOD: In a retrospective study the vertebral metastases of patients with
      prostate cancer (n = 18) were compared to those of patients with tumors of
      another histology (n = 20). A steady-state free precession sequence was used for
      the diffusion-weighted imaging. Additionally, a T1 weighted sequence before and
      after administration of contrast agent as well as a fat suppressed T2 weighted
      sequence were performed. The contrast behavior of the metastases was evaluated
      for all four sequences and was compared to that of the unaffected parts of the
      vertebra. RESULTS: In 18 patients of the tumor group, the vertebral metastases
      showed positive contrast in the diffusion-weighted images, and 2 had minimally
      negative contrast up to - 0.04. In the prostate cancer group, the contrast was
      positive in 9 patients and negative in 9. 6 of the metastases with negative
      contrast had an osteoblastic metastasization, 1 had an osteolysis, and 1 had a
      normal finding in the conventional X-ray image. Between the tumor group and the
      prostate cancer group, the medians of the contrasts were not significantly
      different (p = 0.054). CONCLUSION: In general, the metastatically affected
      vertebrae appear hyperintense in the diffusion-weighted images. This observation
      is only true for some vertebral metastases due to prostate cancer. The cause for
      this seems to be the degree of sclerosis of the metastases. Thus, it cannot be
      generally deduced from the hypointensity in diffusion-weighted images that a
      lesion is benign.

PMID- 16612732
TI  - [Transfemoral catheter embolization of a hepatic pseudoaneurysm after surgical
      therapy of traumatic liver rupture].

PMID- 16612733
TI  - [Massive cerebral air embolism after computerized tomography guided lung biopsy].

PMID- 16612734
TI  - [Extravasation of contrast medium after coronary angiography simulates
      subarachnoid hemorrhage].

PMID- 16612735
TI  - [Spontaneous dissection of the internal carotid artery with ipsilateral Collet
      Sicard syndrome].

PMID- 16612736
TI  - [Pancreatic tuberculosis--a diagnostic chameleon].

PMID- 16612737
TI  - [Pancreas anulare as an incidental finding in multidetector computer tomography
      for symptomatic abdominal aortic aneurysm].

PMID- 16612738
TI  - Power responses of a rowing ergometer: mechanical sensors vs. Concept2
      measurement system.
AB  - The aim of this study was to compare the power provided by a recent ergometer
      with the power developed by the rower determined using mechanical sensors set on
      the same apparatus. Six rowers and six non-rowers performed a power graded test
      and an all-out start on an instrumented ergometer (Concept2 system, model D,
      Morrisville, VT, USA). Power values displayed by the ergometer were recorded with
      a specific software. A strain gauge placed near the handle and a position sensor
      installed on the chain allowed the calculation of the power developed by the
      rower. Power values provided by the ergometer were strongly correlated to those
      determined with a direct measurement and calculation of power. However, power
      values given by the Concept2 system were lower (- 17.4 to - 72.4 W) than those
      calculated using mechanical sensors. This difference in power measurements was
      lower at a steady pace and for rowers. The Concept2 system underestimates the
      power produced by the rower by approximately 25 W. This difference in power seems
      to be independent of the level of power developed but increases with variations
      in intensity and pace. The deletion of the first strokes following changes in
      power production allows to limit this phenomenon. According to the use of the
      power parameter in the experimental design, it could be appropriate to correct
      values provided by the Concept2 ergometer.

PMID- 16612739
TI  - Pulmonary O2 uptake on-kinetics in endurance- and sprint-trained master athletes.
AB  - The purpose of this study was to characterise the VO2 kinetic response to
      moderate intensity cycle exercise in endurance-trained (END) and sprint or power
      trained (SPR) track and field master athletes ranging in age from 45 to 85 years.
      We hypothesised that the time constant (tau) describing the Phase II VO2 on
      response would be smaller in the END compared to the SPR athletes, and that the
      tau would become greater with increasing age in both groups. Eighty-four master
      athletes who were competing at either the British or European Veteran Athletics
      Championships acted as subjects, and were classified as either END (800 m -
      marathon; n = 41), or SPR (100 - 400 m and field events; n = 43) specialists.
      Subjects completed two 6 minute "step" transitions to a work rate of moderate
      intensity on a cycle ergometer and pulmonary gas exchange was measured breath-by
      breath. Analysis of variance revealed that SPR athletes had slower VO2 on
      kinetics (i.e., greater tau) compared to END athletes at each of the age groups
      studied: 46 - 55 yrs (END: 25 +/- 6 vs. SPR: 36 +/- 9 s; p < 0.10), 56 - 65 yrs
      (END: 25 +/- 5 vs. SPR: 35 +/- 10 s; p < 0.05), 66 - 75 yrs (END: 29 +/- 10 vs.
      SPR: 40 +/- 13 s; p < 0.05), and 76 - 85 yrs (END: 31 +/- 10 vs. SPR: 51 +/- 18
      s; p < 0.05). The VO2 on-kinetics became slower with advancing age in the SPR
      athletes (p < 0.05 between 56 - 65 and 76 - 85 yrs) but were not significantly
      changed in the END athletes. The slower VO2 on-kinetics in SPR compared to END
      master athletes is consistent both with differences in physiology (e.g., muscle
      fibre type, oxidative/glycolytic capacity) and training between these specialist
      athletes. Master END athletes have similar tau values to their younger
      counterparts (approximately 25 s) suggesting that participation in endurance
      exercise training limits the slowing of VO2 on-kinetics with age in this
      population.

PMID- 16612740
TI  - Evaluation of the energy expenditure in competitive swimming strokes.
AB  - The purpose of this study was to measure and compare the total energy expenditure
      of the four competitive swimming strokes. Twenty-six swimmers of international
      level were submitted to an incremental set of 200-m swims (5 swimmers at
      Breaststroke, 5 swimmers at Backstroke, 4 swimmers at Butterfly and 12 swimmers
      at Front Crawl). The starting velocity was approximately 0.3 m x s (-1) less than
      a swimmer's best performance and thereafter increased by 0.05 m x s (-1) after
      each swim until exhaustion. Cardio-pulmonary and gas exchange parameters were
      measured breath-by-breath (BxB) for each swim to analyze oxygen consumption (VO2)
      and other energetic parameters by portable metabolic cart (K4b(2), Cosmed, Rome,
      Italy). A respiratory snorkel and valve system with low hydrodynamic resistance
      was used to measure pulmonary ventilation and to collect breathing air samples.
      Blood samples from the ear lobe were collected before and after each swim to
      analyze blood lactate concentration (YSI 1500 L, Yellow Springs, Ohio, USA).
      Total energy expenditure (E(tot)), was calculated for each 200-m stage. E (tot)
      differed significantly between the strokes at all selected velocities. At the
      velocity of 1.0 m x s (-1) and of 1.2 m x s (-1) the E(tot) was significantly
      higher in Breaststroke than in Backstroke, in Breaststroke than in Freestyle and
      in Butterfly than in Freestyle. At the velocity of 1.4 m x s (-1), the E(tot) was
      significantly higher in Breaststroke than in Backstroke, in Backstroke than in
      Freestyle, in Breaststroke than in Freestyle and in Butterfly than in Freestyle.
      At the velocity of 1.6 m x s (-1), the E(tot) was significantly higher in
      Breaststroke and in Butterfly than in Freestyle. As a conclusion, E(tot) of well
      trained competitive swimmers was measured over a large range of velocities
      utilising a new BxB technique. Freestyle was shown to be the most economic among
      the competitive swimming strokes, followed by the Backstroke, the Butterfly and
      the Breaststroke.

PMID- 16612741
TI  - ACTN3 genotype in professional endurance cyclists.
AB  - The Z-disk protein alpha-actinin-3 is only expressed in type II muscle fibres,
      which are responsible for generating forceful contractions at high velocity.
      Despite the evolutionary conservation of alpha-actinin-3, approximately one in
      every five Caucasians of European ancestry is totally deficient in this protein,
      due to homozygosity for a R577X polymorphism in the ACTN3 gene. This, together
      with the results of recent research on elite athletes, suggests that the "null"
      XX polymorphism might confer some advantage to endurance performance events. To
      test this hypothesis, we studied the frequency distribution of R577X genotypes in
      a group of 50 top-level male professional cyclists (26.9 +/- 0.4 yrs [mean +/-
      SEM]; VO2max: 73.5 +/- 0.8 ml x kg (-1) x min (-1)). Their results were compared
      with those of a group of 52 Olympic-class male endurance runners (26.8 +/- 0.6
      yrs; VO2max: 73.3 +/- 0.8 ml x kg (-1) x min (-1)) and 123 healthy, sedentary
      male controls. All subjects were Caucasian, and of European ancestry. No
      significant differences (p > 0.05) were found between groups: RR: 28.5 %; RX:
      53.6 % and XX: 17.9 % in controls; RR: 28.0 %; RX: 46.0 % and XX: 26.0 % in
      cyclists; and RR: 25.0 %; RX: 57.7 %; XX: 17.3 % in runners). No differences were
      found in indices of endurance performance (VO2peak or ventilatory thresholds)
      between athlete carriers of each R577X genotype. In summary, although the alpha
      actinin-3 deficient XX genotype may be detrimental for sprint performance in
      humans, the R577X polymorphism of the ACTN3 gene does not appear to confer an
      advantage on the ability of male athletes to sustain extreme endurance
      performance.

PMID- 16612742
TI  - Effect of physical fitness and endurance exercise on indirect biomarkers of
      recombinant growth hormone misuse: insulin-like growth factor I and procollagen
      type III peptide.
AB  - Serum insulin-like growth factor-I (IGF-I) and procollagen type III peptide (P
      III-P) have been proposed as indirect biomarkers of rhGH misuse in sports. The
      purpose of the present study was to investigate concentrations of these
      biomarkers in athletes at different levels of physical fitness and endurance
      exercise. Serum total IGF-I and P-III-P were measured in 96 elite athletes of
      various sports along the training season; in 21 recreational athletes at baseline
      non-exercising conditions and in another 129 recreational athletes before and
      after long-distance races (10 and 21 km). No differences were evidenced for IGF-I
      concentrations, but statistically higher values of serum P-III-P were found in
      elite athletes compared to recreational ones. Among elite athletes, the specific
      sport did not affect serum IGF-I. However, P-III-P was statistically higher in
      the sport performed by the youngest athletes (rhythmic gymnastics), even after
      correction of the logarithm of the concentration by the reciprocal of age. Over
      the training season, the within-athlete variabilities of IGF-I and P-III-P in
      elite athletes were low (22.8 % and 21.7 %, respectively). Recreational athletes
      taking part in a 21 km competition race showed a significant increase in serum
      values of IGF-I and P-III-P immediately after the event. Exercise workload and
      age had a significant effect on serum concentration of P-III-P, while age alone
      affected IGF-I serum concentrations. Therefore, athlete's reference concentration
      ranges for doping detection should include subjects from as many different ages
      and sports as possible.

PMID- 16612743
TI  - Cardiorespiratory responses of Hi Fit and Low Fit subjects to mental challenge
      during exercise.
AB  - The influence of psychological states on physiological responses during exercise
      is of considerable importance to individuals for which the efficiency of energy
      production is critical to occupational performance. Numerous studies have shown
      that aerobic fitness is associated with enhanced cardiovascular efficiency at
      rest and that responses to mental stress demonstrate evidence of increased
      sensitivity (relative increase in HR response) and enhanced efficiency (a
      decrease in absolute HR). However, the effect of aerobic fitness and its impact
      on cardiorespiratory (CR) responses to psychological stress during exercise has
      not been investigated. Therefore, the purpose of this study was three-fold; (1)
      to examine during exercise, anxiety, effort sense, and CR responses to a mental
      challenge, (2) to examine anxiety and heart rate (HR) responses from rest to
      exercise with mental challenge between below average fitness (Low Fit) and well
      above average fitness (Hi Fit) individuals (exercising at similar relative
      intensities), and (3) to examine anxiety, effort sense, and CR responses of Low
      Fit and Hi Fit individuals to a mental challenge during exercise at a similar
      relative intensity. Twelve Low Fit and eleven Hi Fit subjects participated in
      two, 32-minute cycle ergometer rides at 65 % of VO2max. In the mental challenge
      condition (MCC), subjects rode while participating in mentally challenging tasks
      (Stroop Color-Word task and mental arithmetic) from min 6 to min 14 of the
      protocol. In the no mental challenge condition (NMCC), subjects exercised at the
      same intensity and duration without a stressor. Subjects were counter-balanced
      between fitness levels and condition. HR, VE, VE/VO2, RR, VO2, RER, effort sense
      (RPE), and state anxiety (SAI) were assessed at 5, 14, 24, and 30 min. SAI was
      also assessed at - 5 min before exercise and after 15 min of recovery. In
      addition, the NASA task load index (NTLX) was used to assess perceived overall
      workload. SAI increased significantly at 14 min in the MCC. NTLX scores indicated
      that the MCC was perceived as a greater overall workload. Furthermore, HR, VE,
      VE/VO2, and RR were significantly elevated during the mental challenge condition
      at 14 min. The Hi Fit subjects tended to respond to the dual stress of exercise
      and mental challenge with a relative increase in HR, while absolute HR was
      similar in both groups. An examination of fitness group differences revealed that
      SAI and NTLX were similar for Low Fit and Hi Fit subjects when exercising in the
      MCC, although, Hi Fit subjects demonstrated lower HR responses from 6 min to 14
      min. VE, VE/VO2, and RR were similar for Low Fit and Hi Fit subjects. These
      results suggest that psychological stress during physical activity can exacerbate
      cardiorespiratory responses and suggests that factors that impact CR adjustment
      to mental challenge from resting baseline may differ from the factors that impact
      CR adjustment to mental challenge during exercise. Finally, fitness level
      attenuates HR and may attenuate additional cardiorespiratory responses while
      participating in a dual stress condition, of exercise and mental challenge.

PMID- 16612744
TI  - The use of acetic acid in magnification chromocolonoscopy for pit pattern
      analysis of small polyps.
AB  - BACKGROUND AND STUDY AIMS: The role of acetic acid spray during magnification
      chromocolonoscopy has not previously been evaluated. We aimed to compare the
      accuracy of predicting polyp histology at magnification colonoscopy, using acetic
      acid and indigo carmine, either alone or in combination. PATIENTS AND METHODS: A
      total of 46 consecutive patients with polyps detected during colonoscopy which
      measured 10 mm or less were alternately divided into two groups. In group A
      patients, 1.5 % acetic acid was applied to the mucosa first, followed by indigo
      carmine spray; in group B patients, the order was reversed. The pit pattern was
      assessed after application, in real time. All the lesions were resected and
      examined histologically. RESULTS: Altogether, 37 adenomas and 36 hyperplastic
      polyps were evaluated. In group A, the diagnostic accuracy after spraying with
      acetic acid was 95 %, which increased to 98 % after application of indigo
      carmine. In group B, the accuracy after indigo carmine application was 83 %.
      After subsequent spraying with acetic acid, images were enhanced in 70 % of
      patients, with an increase in accuracy to 97 %. The mean time required to obtain
      an initial clear image with the first dye was 14 seconds for both groups.
      CONCLUSIONS: This is the first description of the use of acetic acid for pit
      pattern analysis of colonic polyps. Its ease of use, low cost, and safety,
      together with its excellent accuracy in the assessment of polyp pit patterns
      suggest that this method could easily be applied to routine magnification
      colonoscopy.

PMID- 16612745
TI  - Segmental colitis associated with diverticula: a 7-year follow-up study.
AB  - BACKGROUND AND STUDY AIMS: We performed a long-term follow-up study of patients
      with segmental colitis associated with diverticula, in order to clarify the
      natural history of this disease. PATIENTS AND METHODS: We identified 15 patients
      who were diagnosed as having segmental colitis associated with diverticula during
      1997. We assessed these patients by means of periodic follow-up visits from 1997
      to 2004. RESULTS: Eight of the 15 patients had no clinical recurrence during
      follow-up. Five patients had sporadic recurrences that were clinically mild (on
      average, one in 5 years), which responded to topical therapy and often to self
      medication. Only two patients were diagnosed during the follow-up period as
      having Crohn's disease; notably, these were the only patients who did not have
      hematochezia as the main symptom at onset. CONCLUSION: The course of this disease
      appears to be substantially benign.

PMID- 16612746
TI  - Evaluation of the effectiveness of an enzymatic cleaner and glutaraldehyde-based
      disinfectant for chemothermal processing of flexible endoscopes in washer
      disinfectors in accordance with prEN ISO 15 883.
AB  - BACKGROUND AND STUDY AIMS: This study evaluated the effectiveness of the cleaning
      process, the disinfection process, and a combination of the two in accordance
      with the new international standard, prEN ISO 15 883. MATERIALS AND METHODS: The
      cleaning process consisted of a 1-min prerinse at 20 degrees C, followed by a 5
      min cleaning step at 45 degrees C (with an enzymatic cleaner, 0.5 %), followed by
      a 1-min interim rinse from 45 degrees C to 55 degrees C. The disinfection process
      consisted of a 1-min prerinse at 20 degrees C, followed by a 5-min disinfection
      step at 55 degrees C (with a glutaraldehyde-based disinfectant, 1 %), followed by
      two final rinses of 1 min each at 55 degrees C. Transparent test pieces were
      contaminated with a mixture of blood and ENTEROCOCCUS FAECIUM, and were assessed
      for visible cleanliness and microbial load. RESULTS: Cleaning alone, disinfection
      alone, and the combination of the two always led to visible cleanliness of all
      test pieces. The cleaning process revealed a mean reduction factor of > or = 4.6
      (n = 6); the disinfection process revealed a mean reduction factor of > or = 9.0
      (n = 6), and the combination of the two was found to reduce the test organism in
      the WD440 by 9.0 +/- 0.2 log (10) steps (n = 12) and in the AdaptaScope by 9.3 +/
      0.4 log (10) steps (n = 5). CONCLUSIONS: Overall, the entire process was found
      to be very effective and compatible for reprocessing flexible endoscopes in
      washer-disinfectors. No visible residual blood was found, despite the use of
      glutaraldehyde in the disinfection phase. These findings once again emphasize the
      importance of effective cleaning for the overall results when reprocessing
      flexible endoscopes.

PMID- 16612747
TI  - [Ultrastructural analysis of secretion-transport through the parotid duct].
AB  - BACKGROUND: Mechanisms of secretion transport through the parotid duct (stenon's
      duct) and their influence on diseases of the parotid gland have not been
      investigated sufficiently until today. METHODS: According to this background we
      performed histologic and scanning electron microscopical investigations of 23
      parotid ducts in order to investigate the arrangement of fibrillar structures of
      the duct as well as get deeper insights into the physiology of secretion
      transport mechanisms. RESULTS: The subepithelial soft tissue of the parotid duct
      could be divided into two layers. The inner layer measured about 100-200 microm
      and consisted of collagen and elastic fibres running in a spiral arrangement. The
      outer layer varied in its thickness and was composed of collageous fibres, which
      were mostly arranged longitudinally. CONCLUSIONS: The arrangement of collagen
      fibrils in the wall of the parotid duct seems to influence secretion transport.
      Due to the spiral organization of collagen fibrils, distension of the duct is
      likely to be associated with a "wring-out" mechanism leading to unidirectional
      transport of saliva into the oral cavity. A muscular sphincter at the outlet of
      the parotid duct did not exist. The duct pierced the buccinatory muscle. Here, it
      was surrounded by sceletal muscle fibres that lead to a functional closure during
      contraction. Our results indicate that an active transport of saliva through the
      parotid duct--as so far assumed--is unlikely.

PMID- 16612748
TI  - [Paraganglioma of the head and neck--tumor control, functional results and
      quality of life].
AB  - BACKGROUND: Surgical therapy for paragangliomas (PG) of the head and neck is, due
      to the alternatives of radiation therapy and wait-and-scan strategy and because
      of postoperative morbidity, under ongoing discussion. MATERIAL AND METHODS:
      Between 1981 and 2004, 79 patients with 94 PG of the head and neck were treated
      at our department. These patients had follow-up examination within a clinical
      trial considering tumor control, functional results and for the first time
      neuropsychologically evaluated postoperative quality of life. Mean follow-up time
      was 65 months (1 to 228 months). RESULTS: Among the 94 PG there were 19 carotid
      body (GCP), 12 vagal nerve (GVP) and 63 jugular-tympanal paragangliomas (JTP). Of
      these, 87 tumors underwent surgery. In 68 patients (78.1 %), the tumor could be
      removed completely. In particular, complete resection of GCP was achieved in 100
      %, of GVP in 90.9 %, of JTP type A in 100 %, of JTP type B in 83.3 %, of JTP type
      C in 66.6 % and of JTP type D in 61.5 %. During the follow-up period, residual or
      recurrent tumors were diagnosed in 17 patients (19.5 %). Six of the seven
      residual PG were observed by magnetic resonance tomography and did not show
      growth. One residual PG and 6 recurrencies were resected completely. One
      recurrent tumor was radiated and 3 others are under observation without showing
      growth tendencies. Two patients died postoperatively due to borderline operations
      of extended tumors. The quality of life after PG surgery showed a SIP of 4.8,
      which is comparably much better than after acoustic neuroma surgery (SIP 10.3).
      CONCLUSION: Whereas complete tumor resection of GCP and JTP types A and B is
      almost ever possible without cranial nerve palsies, surgery of GVP and advanced
      JTP causes often severe functional deficits. However, postoperative quality of
      life is mostly good. Nevertheless, advanced PG require an individualized
      therapeutic regime also including radiation and observation of tumor growth.

PMID- 16612749
TI  - [ENT relevant changes in the German OPS Procedure Classification System for
      2006].
AB  - BACKGROUND: Classification of surgical and medical procedures is of increasing
      relevance for health care financing. From this viewpoint, classification
      according to the German "Operations- und Prozedurenschlussel" (OPS) was
      frequently inadequate so far. METHODS: In the course of a comprehensive DRG
      evaluation project, deficits of the economic classification of ENT-medicine were
      identified. Based on these findings, proposals for further improvement of the OPS
      were developed. RESULTS: An improper medical economic classification was
      identified for common surgical procedures on middle ear, nose and paranasal
      sinuses, and for coding of prosthetic voice restoration. In agreement with the
      German Institute for Medical Documentation and Information (DIMDI) the OPS was
      revised accordingly. CONCLUSIONS: Significant modifications of the OPS will take
      place at January 1 (st) 2006, which are of great impact for health care financing
      by the G-DRG-System and in the context of outpatient surgery.

PMID- 16612750
TI  - [Information before tumor extirpation at the neck].

PMID- 16612751
TI  - [Phoneme discrimination test material for preschool children: development and
      preliminary assessment].
AB  - BACKGROUND: Several tests have been developed to probe phoneme discrimination.
      However, little is known about the reliability and validity of discrimination
      abilities in preschool children as assessed by these tests. Based on previous
      results we now developed a test material based on minimal pair presentation.
      METHODS: Prospective study; 30 preschool children (5;1 to 6;3 years old, 17 boys,
      13 girls); descriptive statistics and correlational analysis; items: 60 minimal
      pairs consisting of real words and nonsense words. RESULTS: Empirical testing
      confirmed prediction of normal distributed phoneme discrimination errors. No
      gender specific effects were found. Results correlated with the degree of phoneme
      opposition and with phonological loop capacity. DISCUSSION: These results
      indicate that the test material developed is suitable for testing phoneme
      discrimination in preschool children. However other normative assessments using
      larger test populations are warranted. Phoneme discrimination tasks appear to
      include testing of sensory as well as linguistic-cognitive functioning.

PMID- 16612752
TI  - [Neurotrophic factors of the GDNF family and their receptors are detectable in
      spiral ganglion cells of normal hearing as well as of deafened rats].
AB  - BACKGROUND: Recent studies have shown that neurotrophic factors like BDNF, NT-3
      and GDNF induce protective effects on spiral ganglion cells after noise- or drug
      induced hearing loss. According to these studies it is suggested that deafness
      leads to a lack of neurotrophic factor or relating receptor expression in spiral
      ganglion cells, that has to be compensated by local cochlear application of these
      factors. METHODS: In the present study we examined the expression pattern of
      members of the GDNF family (GDNF, Neurturin, Artemin, Persephin) and their
      relating receptors (Ret, GFRalpha1 - 3) as well as BDNF and trkB on spiral
      ganglion cells of normal hearing and experimentally deafened rats (10 %
      neomycine). Indirect immunofluorescence was carried out to determine protein
      expression of these factors and their receptors 26 days following deafening.
      RESULTS: Our results demonstrate neurotrophic factor and receptor expression on
      spiral ganglion cells of normal hearing as well as experimentally deafened
      animals. CONCLUSIONS: Our data indicate that within a period of 26 days after
      deafening no detectable reduction of the GDNF-family member expression and their
      receptors was ascertainable on spiral ganglion cells by immunohistochemistry.
      Thus, a lack of neurotrophic factor expression is unlikely to be the only cause
      of spiral ganglion cell loss following deafening.

PMID- 16612753
TI  - [Comparison of gold-plated silver- and silver oxide-impregnated silastic
      tympanostomy tubes: a randomized, prospective clinical trial].
AB  - The insertion of tympanostomy tubes is the most common surgical procedure in the
      world. A major complication of chronic intubation is infectious otorrhea. The
      present study compares the rate of infectious otorrhea and survival rate of gold
      plated silver tubes (GPR) vs. Silver Oxide-Impregnated Silastic Tubes (SPR).
      STUDY DESIGN: The prospective, randomized clincial trial was conducted with 116
      children (59 female, 57 male) aged between 16 and 127 months (median: 51 months).
      Bilateral insertion of ventilation tubes was performed with SPR on one side and
      GPR on the other side in all children. The resulting data were compared using 2
      tailed Wilcoxon-test. RESULTS: Out of 116 children, 11 left the study, 26
      children finished the study by extrusion of both tubes, 32 children lost one tube
      and 47 children lost no tube. Total follow-up of GPR and SPR amounted to 703 and
      949 months, respectively. Mean survival rate of SPR and GPR was 9.9 +/- 4.6 and
      7.0 +/- 3.4 months, respectively (p < 0.001). During the first postoperative
      week, 13% of children suffered from otorrhea; after the first postoperative week
      until extrusion of the tubes, otorrhea was observed in 55% of children. The ratio
      otorrhea/months amounted to 0.046 and 0.05 in SPR and GPR, respectively (p: n.
      s.). CONCLUSIONS: Survival rate of SPR is significantly longer than compared to
      GPR. No differences in the otorrhea rate of SPR vs. GPR are detectable. The
      longer survival rate of SPR seems to be independent of the rate of infectious
      otorrhea but depends probably on other effects of biocompatibility.

PMID- 16612754
TI  - [Cognitive group therapy for tinnitus--a retrospecive study of their efficacy].
AB  - BACKGROUND: At the moment there are various possible therapy forms for ear
      noises, for example medicamentous, acoustical, electrical, surgical,
      radiological, behaviour-medical and "alternative" strategies, though a reliable
      curative therapy is not known up to now. However by combination of several
      therapy forms an improvement of the tinnitus aurium is possible. METHOD: Most
      participants of this study first received an infusion therapy for 5 to 15 days
      which improved the blood circulation. In case of an insufficient improvement of
      the patient's discomfort, participation in the psychological support at the
      Tinnitus-Therapy-Centre was recommended. Both a psychological immunization
      (Psychologisches Immunisierungstraining) and the auditive stimulation therapy
      were part of the measures of intervention. The patients acquired methods of
      relaxing and easing, like Progressive Muscle Relaxation according to Jacobson,
      cognitive restructuring methods as well as attention-steering techniques. Beyond
      that the healing process was strengthened with relaxing music. PATIENTS: In
      retrospective view in a period of nearly 6 years over 500 patients were asked
      about their discomfort by the Tinnitus questionnaire (TQ) by Goebel and Hiller at
      the beginning and at the end of their group therapy. RESULTS: The evaluation
      shows an improvement of the score at 93.2% of all treated patients, whereby with
      6.8% of the participant a stagnation and/or a degradation of the scores could be
      detected in the TQ. On average the value after the treatment improved at around
      16 points. CONCLUSION: In comparison with the stationary treatment this therapy
      represents a meaningful treatment alternative, which is accepted by health
      insurance companies.

PMID- 16612755
TI  - [Neurotrophic factor expression in vestibular schwannoma. An overview].
AB  - The vestibular schwannoma is a benign, slow-growing neoplasm that originates from
      the neurolemmal sheath of the vestibular branch of the VIIIth cranial nerve. This
      tumor entity accounts for 6 % of all intracranial tumors and the annual incidence
      of newly diagnosed vestibular schwannoma is reported as 13 per million. The
      molecular pathogenesis of both sporadic vestibular schwannoma and those occurring
      in neurofibromatosis type II appears to be associated with an aberration of a
      tumor suppressor gene on chromosome 22q12. The biological background for the
      various growth patterns of vestibular schwannoma is, however, largely unknown.
      This differing clinical and biological behaviour of vestibular schwannoma may be
      explained by the presence of neurotrophic factors. The results of recent
      immunohistochemical studies demonstrate the co-expression of transforming growth
      factor (TGF)-beta 1 and glial cell line-derived neurotrophic factor (GDNF) in
      vestibular schwannoma and suggest a trophic synergism of both neurotrophic
      factors in this tumor. Moreover, expression of numerous different neurotrophic
      factors has been shown in studies of nerve growth factor (NGF), vascular
      endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast
      growth factor (FGF), neuregulin (NRG) and erythropoietin (EPO) indicating a
      biological role in development, maintainance or growth of vestibular schwannoma.
      In this article, we summarize the findings on neurotrophic factor expression and
      discuss their characteristics and biological role in vestibular schwannoma.

PMID- 16612756
TI  - [Significance of PET and integrated PET/CT in the diagnostics of occult primary
      tumors].
AB  - BACKGROUND: In the last years (18)F-FDG-positron-emission-tomography (PET) worked
      satisfactorily as helpful auxiliary method in order to verify recurrency of head
      and neck tumors and to detect primary tumors in case of CUP syndrome especially
      when CT and MR imaging failed to identify the tumor accurately. Fusion of FDG
      hypermetabolism in PET scan and anatomical structures is achieved by integrating
      positron emission tomography with CT and provides improvement also in case of CUP
      syndrome. This retrospective study shows 47 patients with neck metastases where
      PET or PET/CT helped to detect primary tumor site. PATIENTS: In a retrospective
      investigation 49 PET studies of 47 patients with CUP syndrome were analyzed.
      RESULTS: 9 cases had positive PET findings, 1 case false-positive. 5 cases were
      false-negative. In 40 PET studies there couldn't be found any sign of suspicious
      FDG hypermetabolism. CONCLUSION: PET and PET/CT deliver a certain improvement in
      localization of primary tumor site and therapeutical strategy.

PMID- 16612757
TI  - [Clinical use of a voice prosthesis with a flap valve containing silver oxide
      (Blom-Singer Advantage), biofilm formation, in-situ lifetime and indication].
AB  - BACKGROUND: Fungal growth and the resulting leakage through an indwelling voice
      prosthesis remains the most frequent reason of prosthesis failure and renewal. In
      some patients leakage caused by fungal growth occurs in very short intervals
      (below 12 weeks in-situ lifetime) and causes frequent treatments and high costs.
      METHODS: The Blom-Singer(R) Advantage voice prosthesis is a new prosthesis type
      with a modified flange design, a flap valve containing 7 % silver oxide in the
      silicon matrix and is expected to be resistant against biofilm formation and
      fungal growth. PATIENTS: In a clinical trial we used the Blom-Singer(R) Advantage
      prosthesis in 33 patients with short in-situ lifetimes of their voice prosthesis
      and analysed the effects on in-situ lifetime and complications statistically.
      RESULTS: The clinical use of the Blom-Singer(R) Advantage prosthesis was similar
      to other types of indwelling voice prosthesis (Provox(R) II, Blom-Singer
      Indwelling(R)) and did not cause any special problems. Prosthesis specific side
      effects (i. e. allergy against silver oxide) did not occur. Statistical analysis
      of the aquired data showed an interindividually changing, but significantly
      longer in-situ lifetime for the Blom-Singer(R) Advantage prosthesis. The mean
      device lifetime increased from 36 days (median 36 days) to a mean lifetime of 110
      days (median 87 days) with the use of the Blom-Singer(R) Advantage prosthesis.
      CONCLUSIONS: Using a voice prosthesis with a valve containing silver oxide can
      normalize and even increase the in-situ lifetime in patients with frequent
      changing procedures caused by fungal growth on the valve. Therefore we recommend
      the use of this type of voice prosthesis for those patients as reduction of costs
      and effort results.

PMID- 16612758
TI  - [Myositis of the sternocleidomastoid muscle as a result of arthritis of the
      sternoclavicular joint].
AB  - This article describes a rare case of a myositis of the sternocleidomastoid
      muscle due to an acute septic arthritis of the sternoclavicular joint. A 51-year
      old male in reduced condition was admitted to the Department of
      Otorhinolaryngology with a one-week history of a painless swelling of the
      sternocleidomastoid muscle associated with recurrent fever. Physical examination
      was otherwise unremarkable. An intravenous antibiotic therapy was initiated
      without improvement of the process, accordingly a specific infection or a
      malignancy was ruled out by biopsy. The positron emission tomography and magnetic
      resonance imaging finally revealed the diagnosis of a septic arthritis of the
      sternoclavicular joint as the causal focus of the infection. After an extensive
      surgical debridement and under continued antibiotic therapy the patient made an
      uneventful recovery. The acute septic arthritis of the sternoclavicular joint is
      an uncommon infection with an insidious onset and is often unrecognized until it
      spreads to adjacent structures leading to serious complications. This case
      emphasizes that a myositis of sternocleidomastoid muscle can be caused by an
      ascending infection due to an acute septic arthritis of the sternoclavicular
      joint. Clinical course, diagnosis and treatment of this uncommon disease are
      reviewed in this article.

PMID- 16612759
TI  - [Myositis ossificans of the neck in a 47 year old patient].
AB  - BACKGROUND: Myositis ossificans is a heterotopic ossification of the soft tissue,
      which leads in progredient cases to functional disorder. Cervical localization is
      a rare entity. The clinical symptoms are more or less unspecific. Indicating is a
      foregoing trauma of the affected region. CASE REPORT: We report about a 47 year
      old male patient with a dorsocervical mass, which had caused dysfunction. He was
      operated after the diagnosis had been histologically and radiologically
      confirmed. CONCLUSIONS: In case of cervical tumors with radiological evidence of
      partial calcification differential diagnosis should keep in mind myositis
      ossificans next to tuberculosis or sarcoma. Surgery and postoperative prophylaxis
      with Indometacin is the therapy of choice.

PMID- 16612760
TI  - [Titanium oxide ceramic as an implantation material in otosurgery: animal
      experimental results and surgical technique].
AB  - BACKGROUND: For the experimental animal study to evaluate a new ossicular chain
      replacement prosthesis, we developed a new technique for surgical implantation
      into the middle ear of rabbits. The selection of the species was based on its
      similarity to human middle ear anatomy and the favored, standardized,
      microsurgical approach to the middle ear cavity. METHOD: For the study we
      included a total of 34 approximately 6-month-old female white rabbits (New
      Zealand) with a weight of 3.2 to 4.4 kg. The implants used were constructed of
      ceramic materials TiO(2) (titania) with different pore size. Directly before the
      implantation of the TORPs, as well as at 28, 84 and 300 days after implantation,
      electric response audiometry was used to determine the hearing thresholds of the
      animals (bone conduction click stimulus nHL). The Erbium Yag-Laser was used to
      cut out the originally ossicular chain. RESULTS: After implantation we could not
      detect any stenosis of the outer ear canal or perforation of the tympanic
      membrane. The conductive hearing threshold was in the range of 4.21 +/- 6.68 dB
      nHL (n = 131). The hearing level showed no significant difference before and
      after surgery (p > 0.05). CONCLUSIONS: The laser surgery is a very safe procedure
      for prosthesis implantation in the middle ear of rabbits..

PMID- 16612762
TI  - The eosinophil: the cell and its weapons, the cytokines, its locations.
AB  - Although the functional role of eosinophils is primarily considered to be host
      defense against parasitic infection, current studies indicate that this complex
      cell is ideally adapted for other roles that may involve immune modulation and
      tissue repair. The eosinophil is an important source of basic proteins, lipid
      mediators, cytokines, and growth factors. In disease states, eosinophil
      mobilization from the marrow and circulation can be very rapid yet highly
      organized and cell selective, particularly in response to interleukin (IL) 5 and
      eotaxin. Such elaborate recruitment is regulated by a series of interactions by
      eosinophil receptors and the endothelium and extracellular matrix ligands.
      Several priming mechanisms activate the eosinophils during this recruitment
      process so that the cell arrives at its tissue destination prepared for immediate
      action and prolonged tissue survival. Degranulation is strictly controlled and
      allows the cell to differentially release its contents in an ordered manner. This
      is essential to prevent injury to tissue during migration. Therapy is still
      limited for eosinophil-driven diseases, but intervention at the key events that
      govern eosinophil recruitment and effector function may be the way forward.

PMID- 16612763
TI  - Eosinophilic airway disorders.
AB  - Diseases of the airway are common and make up a significant proportion of the
      respiratory physician's workload. The major contributors to this situation, such
      as asthma, chronic obstructive pulmonary disease (COPD), and chronic cough, all
      result from airway inflammation and often have an overlapping clinical picture,
      which in some instances makes accurate clinical diagnosis difficult. Asthma is a
      condition characterized by variable airflow obstruction, airway hyper
      responsiveness, and airway inflammation, which is usually eosinophilic. However,
      the relationship between eosinophilic inflammation and asthma is complex, with
      only a weak correlation between the severity of airway inflammation and the
      markers of the severity of asthma, such as Pc20 and FEV1. Eosinophilic bronchitis
      is characterized by a chronic cough and sputum eosinophilia without airway hyper
      responsiveness or variable airflow obstruction. The asthma phenotype is
      characterized by microlocalization of mast cells in the airway smooth muscle,
      emphasizing the importance of airway smooth muscle dysfunction in asthma. COPD
      has generally been considered to be a neutrophilic disease, in contrast to
      asthma. However, there is increasing evidence that a significant subgroup exists
      consisting of patients with stable COPD who have chronic airway eosinophilia with
      a more steroid-responsive disease. This article covers the role of eosinophils in
      the airway disorders asthma, COPD, and eosinophilic bronchitis.

PMID- 16612764
TI  - Idiopathic chronic eosinophilic pneumonia.
AB  - Idiopathic chronic eosinophilic pneumonia is a rare disorder of unknown cause
      with nonspecific respiratory and systemic symptoms but rather characteristic
      peripheral alveolar infiltrates on imaging. The disorder is highly responsive to
      oral corticosteroid therapy. However, relapses are frequent when tapering or
      after stopping treatment. Moreover, some patients develop severe asthma at some
      time in the follow-up. The high incidence of relapses and prevalence of severe
      asthma is responsible for the great proportion of patients with idiopathic
      chronic eosinophilic pneumonia who require prolonged oral corticosteroid therapy.
      There are tight links between asthma and idiopathic chronic eosinophilic
      pneumonia. These links might help in the comprehension of the pathogenesis of
      both diseases. Interestingly, there might exist a continuum between
      hypereosinophilic asthma, idiopathic chronic eosinophilic pneumonia, and the
      Churg-Strauss syndrome.

PMID- 16612765
TI  - Acute eosinophilic pneumonia.
AB  - Acute eosinophilic pneumonia is a sudden and severe febrile illness that can
      result in life-threatening respiratory failure. Because this disease can mimic
      other diseases causing acute respiratory failure, the diagnosis may be missed or
      delayed. It is clinically distinguishable from other pulmonary eosinophilic
      diseases and can be diagnosed with bronchoalveolar lavage. Treatment with
      corticosteroids results in rapid reversal of respiratory failure and complete
      recovery, generally without relapse. In some patients, acute eosinophilic
      pneumonia may be caused by drugs, tobacco smoke, or other inhaled substances;
      however, in the majority of patients, the condition is idiopathic.

PMID- 16612766
TI  - Churg-Strauss syndrome.
AB  - Churg-Strauss syndrome was originally called "allergic granulomatosis and
      angiitis," describing the combination of eosinophilic inflammation, extravascular
      granulomas, and necrotizing vasculitis occurring in patients with severe asthma.
      It is now classified as a small-vessel vasculitis and, together with Wegener's
      granulomatosis and microscopic polyangiitis, as one of the vasculitides
      associated with antineutrophil cytoplasmic autoantibodies (ANCA). Glucocorticoid
      sparing agents used in the treatment of asthma, such as leukotriene receptor
      antagonists, may unmask this particular form of vasculitis as oral
      glucocorticoids are withdrawn. ANCA occur in 40-75% of patients with active
      disease and typically react with myeloperoxidase. Patients' symptoms are defined
      by various degrees of eosinophilic inflammation and necrotizing vasculitis, which
      may affect any organ. On presentation, Churg-Strauss syndrome needs to be
      differentiated from other eosinophilic pneumonias, idiopathic hypereosinophilic
      syndrome, and Wegener's granulomatosis and microscopic polyangiitis. Churg
      Strauss syndrome remains a rare disease with a poorly understood pathogenesis.
      Treatment consists primarily of glucocorticoids. Patients who have ANCA at the
      time of presentation should be treated according to the treatment principles for
      ANCA-associated vasculitides. However, the exact role of glucocorticoid-sparing
      immunosuppressive agents and treatment options for refractory disease remain
      poorly studied.

PMID- 16612768
TI  - Parasitic pulmonary eosinophilia.
AB  - Parasitic infections, although common in tropical and subtropical regions, are
      prevalent worldwide because of changing immigration patterns and in international
      travel. The burden of worm infection is enormous and the intensity of infection
      is usually high among the poor and in immunocompromised individuals. Pulmonary
      eosinophilia occurs in almost all metazoan infections. In the Western world, the
      most common infections are caused by Strongyloides, Ascaris, Toxocara, and
      Ancylostoma species. Most of the nematodes multiply within the human host and
      cause pulmonary eosinophilia during larval migration through the lungs. Despite
      larval migration through the lungs, there is usually no permanent lung damage.
      The result is an increased number of eosinophils in the airways or lung
      parenchyma with or without peripheral eosinophilia. Loffler's syndrome, visceral
      larva migrans, and tropical pulmonary eosinophilia are the most common infections
      that cause pulmonary eosinophilia. The most serious parasitic eosinophilic lung
      disease is tropical pulmonary eosinophilia, a disorder caused by the filarial
      worms Wuchereria bancrofti and Brugia malayi, in which cases have typically been
      reported to masquerade acute or refractory bronchial asthma. Increasing
      awareness, newer diagnostic techniques, preventative measures, and antiparasitic
      drugs are important in reducing the worldwide morbidity and mortality from
      parasitic helminths and protozoa. This review focuses on common and some uncommon
      causes of pulmonary parasitic eosinophilia and their manifestations, diagnosis,
      and management.

PMID- 16612767
TI  - Hypereosinophilic syndrome: lymphoproliferative and myeloproliferative variants.
AB  - Idiopathic hypereosinophilic syndrome is a largely heterogeneous disorder defined
      as persistent, marked hypereosinophilia of unknown origin complicated by end
      organ damage. Recent research in cellular and molecular biology has led to the
      characterization of distinct underlying hematological disorders, primitively
      involving cells of the myeloid or lymphoid lineage. The ability to classify many
      hypereosinophilic syndrome patients on the basis of pathogenesis of
      hypereosinophilia has radically changed therapeutic perspectives. Indeed,
      imatinib mesylate has become first-line therapy for patients in whom the FIP1L1
      PDGFRalpha fusion gene is detected, whereas corticosteroids remain the mainstay
      for management of patients in whom hypereosinophilia is secondary to the
      overproduction of interleukin 5 by abnormal T-cells. Use of monoclonal anti
      interleukin-5 antibodies in the latter group of patients has a strong rationale
      and could decrease cumulative corticosteroid doses and toxicity. As far as
      prognosis of these disease variants is concerned, hypereosinophilic syndrome
      patients with the FIP1L1-PDGFRalpha fusion gene may develop acute myelogenous
      (eosinophilic) leukemia, whereas those with clonal interleukin-5-producing T
      cells have an increased risk of developing T-cell lymphoma. It is currently
      unclear whether timely therapeutic intervention in such patients could interfere
      with long-term progression toward malignant hematological disorders.

PMID- 16612769
TI  - Allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis is an uncommon but serious respiratory
      condition characterized by chronic airway inflammation and airway damage
      resulting from persistent colonization by and sensitization to the fungus
      Aspergillus fumigatus. The immunopathogenesis of allergic bronchopulmonary
      aspergillosis involves several pathways. Aspergillus allergens stimulate an
      interleukin 5-mediated Th2 pathway responsible for the eosinophilic infiltrate,
      whereas aspergillus proteases promote epithelial activation and a potent
      chemokine response that induces neutrophilic airway inflammation. The resulting
      airway inflammation is intense, involves tissue damage and remodeling, and is
      linked with the severity of bronchiectasis. Treatment involves corticosteroids
      and antifungal therapy with oral azoles. Additional management seeks to monitor
      and control the other disease components of severe asthma, bronchiectasis, and
      disease exacerbations.

PMID- 16612770
TI  - Drug-, toxin-, and radiation therapy-induced eosinophilic pneumonia.
AB  - A significant number of drugs and toxins have been associated with eosinophilic
      pneumonia. Antibiotics and NSAID, are the most commonly reported drugs. Toxins
      suspected to cause eosinophilic pneumonia include cigarette smoke and illicit
      drugs. Drug- or toxin-induced eosinophilic pneumonia is indistinguishable from
      idiopathic acute or chronic eosinophilic pneumonia by clinical, radiographic, and
      histopathologic criteria. The diagnosis is supported by a temporal relationship
      to a drug or toxin. The condition usually resolves with removal from the agent
      and recurs with rechallenge. Treatment involves discontinuation of the offending
      drug or toxin and treatment with corticosteroids in severe respiratory failure.
      There are also mass outbreaks of eosinophilic pneumonia reported, such as the
      toxic-oil syndrome in 1981 and the eosinophilia-myalgia syndrome related to the
      ingestion of L-tryptophan in 1989. A recent report has described an outbreak of
      acute eosinophilic pneumonia found in soldiers in Iraq. Radiation therapy has
      also been associated with the development of eosinophilic pneumonia in patients
      receiving this treatment for breast cancer.

PMID- 16612771
TI  - [Liver resection (part I) -- anatomical basis, indication, and preoperative
      planning].

PMID- 16612772
TI  - [Theo Becker -- surgical pioneer in the former German Democratic Republic].

PMID- 16612773
TI  - [Multimodal treatment of solid carcinoma -- evidence based?].

PMID- 16612774
TI  - [Limited surgical resection versus local endoscopic therapy of early cancers of
      the esophagogastric junction].
AB  - BACKGROUND: Adenocarcinomas of the esophagogastric junction (especially Barrett's
      cancers) are increasingly diagnosed at early stages. The current standard
      treatment - radical resection with extensive lymphadenectomy - has been
      challenged. Limited resection or endoscopic mucosal ablation have been proposed
      as less invasive alternatives. METHODS: Available data regarding limited surgical
      resections and endoscopic interventional procedures are evaluated with respect to
      short- and long-term results (mortality, morbidity, oncologic adequacy, quality
      of life). RESULTS: Limited resection of the esophagogastric junction has been
      proven as safe (low morbidity and mortality) and oncologically adequate procedure
      (low rate of recurrence/excellent long-term survival) with good quality of life.
      The procedure meets the oncological requirements (R0-resection, complete
      resection of potentially tumor-infiltrated lymph nodes and the entire
      precancerous Barrett's esophagus). Reconstruction with interposition of a
      pedicled isoperistaltic jejunal loop prevents reflux and is crucial for achieving
      good postoperative quality of life. In contrast, endoscopic mucosal resection
      (EMR) carries the risk of high recurrence rates (at least 30 %). This has to be
      regarded as an effect of the frequent incomplete resection, multicentric tumor
      growth, the persistence of precancerous Barrett's mucosa and persistence of
      gastroesophageal reflux. Consequently, from the oncological view point, EMR is
      only suited for unicentric mucosal tumors (T1a) in short segments of Barrett's
      esophagus. Reliable preoperative identification of such tumors is, however,
      currently not possible. CONCLUSION: For adequately selected patients with early
      Barrett's cancer, limited resection of the esophagogastric junction is an
      appropriate procedure. Endoscopic mucosa resection (EMR) might gain importance as
      staging tool.

PMID- 16612775
TI  - [Neoadjuvant therapy in oesophageal cancer surgery].
AB  - Neoadjuvant therapy has been implemented to improve the prognosis of patients
      with oesophageal cancer. Operative therapy remains the therapy of choice for
      nonmetastatic disease in patients who can tolerate resection. Adjuvant therapy
      following resection is usually not indicated. For neoadjuvant therapy it seems to
      be confirmed that preoperative radiotherapy has only very little benefit and
      therefore, should not be recommended. Data for preoperative chemotherapy are
      conflicting. Following preoperative combined radio-chemotherapy a complete
      response of tumour can be expected in 20-25 % of treated patients with a marked
      advantage for these patients. However, there are still no markers available
      indicating tumour response before the start of perioperative radio-chemotherapy.
      Recently published meta-analyses confirm a small overall benefit for
      perioperative radio-chemotherapy. However, these data so far have not led to a
      broad agreement on the indication of neoadjuvant therapy in oesophageal cancer.

PMID- 16612776
TI  - [Multimodal treatment of non small cell lung cancer].
AB  - The primary treatment of lung cancer depends on tumor stage. Chest CT scan and
      bronchoscopy are used to define the TNM stage and resectability. In case of lung
      cancer without mediastinal lymph node enlargement or direct mediastinal
      involvement (clinical stage I-IIb + T3N1) surgical treatment is recommended. The
      use of adjuvant chemotherapy has to be defined, but will be indicated in stage II
      and IIIa. Expected 5-year survival achieves 40 to 80 % depending on tumor stage.
      Exceeds the shorter diameter of mediastinal lymph nodes in chest CT scan more
      than 1 cm (or in case of positive PET scan) mediastinoscopy is indicated. In case
      of N2-disease and after tumor response to preoperative chemotherapy (about 60 %)
      secondary resection of the tumor leads to higher 5-year survival rates (20-40 %)
      compared to patients without induction therapy (5-20 %). In these patients and
      after unexpected detection of solitary lymph node metastasis by primary resection
      adjuvant mediastinal radiotherapy should be added. If the tumor has infiltrated
      the mediastinum or the upper sulcus (T3/4) and/or mediastinal lymph nodes are
      obviously tumor burden (e. g. > 3 cm, N2 bulky, N3) radical primary resection may
      not be possible. In these patients combined radio- and chemotherapy induces a
      high percentage of tumor regression and can be used before secondary resection (5
      year survival 5-20 %). Locally advanced tumors infiltrating the main bronchus
      close to the carina or the carina itself and tumors with metastases in the same
      lobe, both without mediastinal lymph node metastases (T3/4N0-1), can be resected
      by sleeve pneumonectomy and lobectomy with satisfactory results respectively. In
      patients with resectable lung cancer and no clinical sign of tumor disease (f. e.
      anemia, weight loss, pain) limited staging procedure with chest CT scan including
      upper abdomen and bronchoscopy is reasonable. In the remaining patients complete
      staging is necessary. We recommend an interdisciplinary approach to patients with
      lung cancer.

PMID- 16612777
TI  - [Treatment of carcinoma of the pancreatic head].
AB  - For patients with carcinoma in the head of the pancreas surgical resection
      remains the only chance of cure. Perioperative mortality could be reduced in the
      last years dramatically, postoperative morbidity, however, remains high. Only a
      small percentage of all patients suffering from pancreas carcinoma are good
      candidates for an operative therapy. The most frequent contraindications are
      metastases in the liver or the peritoneum or a locally too advanced tumor. The
      extent of surgical resection necessary in patients with pancreas carcinoma is
      still in discussion. Even after an operation under curative aspects long term
      results remain disappointing. Median survival still ranges only about 16 months.
      A substantial improvement of long term- survival can only be expected from new
      multimodal therapeutic strategies. Adjuvant chemotherapy should strongly be
      recommended after resection of a pancreas carcinoma. Neoadjuvant therapy on the
      other hand is still an experimental procedure and under evaluation in ongoing
      prospective randomized studies.

PMID- 16612778
TI  - [Efficacy of current adjuvant and neoadjuvant therapeutic concepts in gastric
      cancer?].
AB  - The incidence of gastric cancer in Europe is declining but the prognosis after
      curatively intended surgery remains dismal. In recent years several studies and
      meta-analysis concerning the impact of adjuvant postoperative chemotherapy and
      chemoradiation as well as preoperative chemotherapy were published. This review
      aims to interpret results and to support decision making in individual patients.
      Results of trials on adjuvant chemotherapy were inconsistent and the studies were
      underpowered to detect meaningful but modest advantages. Meta-analyses including
      more than 3 000 patients revealed a significant survival benefit but no specific
      chemotherapy protocol can be regarded an optimal regimen. Postoperative adjuvant
      schedules including cisplatin led to high drop out rates due to toxicity.
      Applying cisplatin and infusional fluorouracil initially after diagnosis as a so
      called neoadjuvant therapy is better tolerated. Two trials testing this approach
      showed a significant survival benefit with preoperative cisplatin and infusional
      fluorouracil as compared to surgery alone. Postoperative chemoradiation was shown
      to be effective concerning local regional relapses and survival benefit in a
      large trial in the US but the majority of patients were treated with less radical
      lymph node dissection than it is routine in Germany. Enrollment of patients in
      prospective trials evaluating the impact of adjuvant and neoadjuvant strategies
      is warranted.

PMID- 16612779
TI  - [Multimodal treatment of colon cancer?].
AB  - Surgical therapy is still the basis of therapy of patients with colon carcinoma.
      Multimodal therapeutical concepts are presently applied as a therapeutical
      standard in the adjuvant therapy and increasingly in the systemic therapy of
      patients with primarily inoperable metastases of the liver to reach a secondary
      operability. Interdisciplinary multimodal therapeutical concepts are even
      accepted within the therapy of metastasized colon carcinomas. There are still
      unanswered questions regarding sequences of palliative systemic therapies and
      their combinations with local ablative methods.

PMID- 16612780
TI  - [Fiction and facts about multi-modal therapy in rectal cancer].
AB  - The prognosis of patients with rectal cancer has been improved significantly
      after introduction of the total mesorectal excision (TME). Just by performing
      TME, the local recurrence rates could be decreased to less than 10 %, independent
      of multi-modal therapeutic concepts. In contrast, the local recurrence rate
      reached 4 to 55 % (median 20 %) in a German multicenter study in 1995 prior to
      the nationwide introduction of TME. The goal of this overview is to compare the
      different concepts in the multi-modal therapy of rectal cancer with their
      advantages and disadvantages based on the current literature. Mentioned will be
      local recurrence rates and survival, but also toxicity, costs and acceptance of
      patients. Furthermore, a preview is given about future developments.

PMID- 16612781
TI  - [Colorectal cancer liver metastases -- neoadjuvant concepts for preoperative down
      sizing].
AB  - Liver resection for colorectal metastases disease can be performed with curative
      intent at low morbidity and mortality. Only 15-30 % of liver metastases are
      amenable to potentially curative resection. Five year survival following primary
      and repeat liver resection has consistently been reported as 25-40 %. Future
      strategies focus at widening the indication and extending therapeutic options.
      The aim of neoadjuvant treatment of irresectable liver metastasis is the
      conversion to secondary resectability either via increasing residual liver mass
      (portal vein embolisation/2-stage resection) and/or reducing tumor load via
      chemotherapy ("down-sizing"). Current data suggest resectability following
      neoadjuvant chemotherapy in around 8 % of cases but varying between 1-33 %.

PMID- 16612782
TI  - [Predictive and prognostic factors in the neoadjuvant/adjuvant therapy of
      gastrointestinal tumors: wishful thinking or reality?].
AB  - Malignant gastrointestinal tumors are still worldwide a very common cause of
      death from cancer. Even though the surgical techniques and the
      neoadjuvant/adjuvant therapies have improved over the last years and multimodal
      concepts in cancer treatment have been established, these types of tumors remain
      a challenge. Therefore predictive/prognostic markers need to be established, to
      be able to tailor chemotherapies and therefore improve efficacy of
      neoadjuvant/adjuvant treatment. Over the last years potential
      predictive/prognostic factors have been characterized by molecular-biological
      technologies: the tumor suppressor gene p53, the cell-cycle regulatory proteins
      p21 and p27, the marker of proliferation Ki-67, the epidermal growth factor
      receptor, HER2/neu, angiogenetic factors (the vascular endothelial growth factor,
      cyclooxygenase 2, thymidine phosphorylase), enzymes involved in the DNA-repair
      system (ERCC1), enzymes involved in the 5-fluorouracil-metabolism (thymidylate
      synthase, dihydropyrimidine dehydrogenase) or other genetic alterations, like the
      loss of heterozygosity or the microsatellite instability. The results of the
      mainly retrospective studies are promising but prospective studies are needed to
      validate those markers in the therapy of gastrointestinal tumors. The goal is
      that we will be able to predict when and with what to treat.

PMID- 16612783
TI  - [Histopathological faults and their importance for staging and therapy].
AB  - There is a variety of mistake sources of histopathological workup of biopsies and
      resection specimen. Among those are the incorrect or missing transmission of
      clinical findings and data. The most critical opportunities for producing
      mistakes are the histopathological examination, diagnosis and classifications.
      Many of these mistakes bear the potential to induce a wrong therapy. Generally,
      the use of forms, check lists and standardized diagnosis sheets may help to
      reduce the mistake rates. Comparison of own data with quality indicators enables
      pathologists to validate their own findings.

PMID- 16612784
TI  - [The laparoscopic pancreas resection].
AB  - Laparoscopic surgery of the pancreas has been used for diagnostic but also for
      therapeutic purposes in increasing number. Case reports and multicenter studies
      summarizing the European and world wide experience have been published recently.
      The results show that laparoscopic surgery can be used for tumor staging of
      pancreatic cancer but also for the treatment of acute necrotizing pancreatitis
      and treatment of chronic pancreatitis, benign cystic lesions and solid tumors. In
      particular left sided pancreatic resection (90 % of the cases) is the preferred
      approach delivering good results. Recent studies show that the conversion rate is
      14 % and mortality can be as low as 0 %. The reoperation rate is 6.3 % and the
      fistula formation is 17 % which is comparable to the results of open pancreatic
      surgery. The postoperative hospital stay seems to be limited to a mean of 7 days
      as compared to pancreatic surgery in the open abdomen. The laparoscopic Whipple
      resection with less than 3 % of the cases in the literature remains the
      exception.

PMID- 16612785
TI  - [Pancreatic heterotopia as a rare diagnosis of a size increasing gastric tumor].
AB  - A 39 years old woman was noted to have a submucosal gastric tumor during
      gastroscopy for cholecystectomy. She was asymptomatic regarding this tumor. The
      patient was primarily observed, but the tumor size increased. The lesion was
      biopsied with a negative result. A local excision with simultaneous endoscopy was
      done laparoscopically. Malignancy was excluded by immediate sectioning.
      Histological examination revealed pancreatic heterotopy Type I by Heinrichs- with
      exocrine and endocrine cells. The patient had an uneventful postoperative course.
      Eight months after resection the patient was free from recurrence and symptoms.

PMID- 16612786
TI  - Early diagnosis of conjoined twins by real-time three-dimensional ultrasound-
      case report and review of the literature.
AB  - In 1:50 000 to 1:100 000 births, conjoined twins occur, caused by incomplete
      division of the embryonic disc more than 13 days after fertilisation. We present
      a case of cephalothoracopagus janiceps, a very rare form of conjoined twins,
      which was diagnosed at 13 weeks of gestation. Three-dimensional and colour
      Doppler ultrasound enabled precise prenatal visualisation of the fusion of the
      foetal head and chest up to the umbilicus. We could demonstrate the presence of
      two foetal hearts connected by an arterio-arterial shunt as well as two pairs of
      upper and lower extremities. After the clear 3-D presentation of the anomaly,
      making the poor prognosis visible, the mother decided to have the pregnancy
      terminated. Autopsy confirmed the prenatal diagnosis.

PMID- 16612787
TI  - [Multislice CT urography (MSCTU): evaluation of a modified scan protocol for
      optimized opacification of the collecting system].
AB  - PURPOSE: To retrospectively quantify opacification of the urinary tract using a
      MSCTU protocol based on furosemide and individual adaptation of urographic
      acquisition delay. MATERIALS AND METHODS: MSCTU examinations obtained from 4-row
      and 16-row CT scanners in 53 patients (35 men, 18 women, average age 59) were
      independently reviewed by two radiologists. MSCTUs were performed using a low
      dose injection of furosemide. No fixed scan delay for urographic image
      acquisition was applied. The urographic timing was individually adapted by
      performing low-dose test images of the distal ureters to display their current
      opacification. Image analysis included grading of the opacification of the
      segmented collecting system. The average urographic delay was calculated.
      Stratified comparisons of mean scores were assessed using the Friedman and
      Wilcoxon tests. The inter-observer kappa value was calculated. RESULTS: The
      calculated median scan delay for patients with normal serum-creatinine levels (n
      = 51) was 418 sec (mean 447 sec; SD, 118 sec). The median number of acquired test
      images was 2 (range 1 - 6 images). The opacification analysis demonstrated that
      98 % of the ICS, 90 % of the proximal, 86 % of the middle, and 83 % of the distal
      ureteral segments showed opacification greater than 90 %. 9.5 % of the distal
      ureteral segments could not be visualized. Statistics did not show significant
      opacification differences between proximal, middle, and distal ureteral segments
      (p > 0.05). The two observers were largely in agreement (kappa coefficient r =
      0.81). CONCLUSION: The analyzed MSCTU technique based on furosemide and scan
      delay timing by means of test images reliably lead to a homogenous opacification
      of the entire upper urinary tract. It features the individual adaptation of MSCTU
      to the excretory rate of the kidneys.

PMID- 16612788
TI  - [E-Learning in radiology; the practical use of the content management system
      ILIAS].
AB  - PURPOSE: Due to the possibility of using different kinds of visualization, e
      learning has the advantage of allowing individualized learning. A check should be
      performed to determine whether the use of the web-based content management system
      ILIAS simplifies the writing and production of electronic learning modules in
      radiology. MATERIALS AND METHODS: Internet-based e-learning provides access to
      existing learning modules regardless of time and location, since fast Internet
      connections are readily available. RESULTS: Web Content Management Systems (WCMS)
      are suitable platforms for imparting radiology-related information (visual
      abilities like the recognition of patterns as well as interdisciplinary
      specialized knowledge). The open source product ILIAS is a free WCMS. It is used
      by many universities and is accepted by both students and lecturers. Its modular
      and object-oriented software architecture makes it easy to adapt and enlarge the
      platform. The employment of e-learning standards such as LOM and SCORM within
      ILIAS makes it possible to reuse contents, even if the platform has to be
      changed. CONCLUSION: ILIAS renders it possible to provide students with texts,
      images, or files of any other kind within a learning context which is defined by
      the lecturer. Students can check their acquired knowledge via online testing and
      receive direct performance feedback. The significant interest that students have
      shown in ILIAS proves that e-learning can be a useful addition to conventional
      learning methods.

PMID- 16612789
TI  - [Whole-heart coronary MR angiography -- initial results].
AB  - PURPOSE: To evaluate a new coronary MR angiography technique covering the whole
      coronary artery tree in one data set acquisition. MATERIALS AND METHODS: Six
      healthy volunteers and 15 patients with known CAD were examined with a navigator
      gated and corrected (NAV) free-breathing 3D steady-state free precession sequence
      covering the whole heart (WH-MRA) (TR = 5.4, TE = 2.7, SENSE factor = 2, 160
      slices, 0.75 mm reconstructed slice thickness, in-plane resolution = 0.99 x 0.99
      mm(2), scan time 14 min [50 % NAV efficiency]) and a vessel targeted 3D SSFP MRA
      sequence (t-MRA) (TR = 5.6 ms, TE = 2.8 ms, 20 slices of 1.5 mm reconstructed
      slice thickness, in-plane resolution = 0.99 x 0.99 mm(2), scan time = 7 min [50 %
      NAV efficiency]). Subjective image quality (4-point scale) and objective image
      quality parameters including vessel sharpness, vessel diameter and CNR were
      calculated for WH-MRA and t-MRA. In patients, the accuracy for detection of
      stenosis larger than 50 % was compared to the accuracy of X-ray coronary
      angiography (XA), which was considered the standard. RESULTS: WH-MRA demonstrated
      good vessel visibility in healthy subjects (100 %) whereas vessel visibility in
      patients was limited (78 % in an 8 segment evaluation). Vessel sharpness was
      inferior to that of t-MRA in patients (37 vs. 42 %) but equal in healthy subjects
      (42 %). Vessel diameter did not differ significantly between WH-MRA and t-MRA.
      CNR was significantly reduced for WH-MRA (CNR 7.4 vs. 11.5). The diagnostic
      accuracy for the detection of CAD was comparable for both MRA approaches (85.5
      vs. 86.2 %). CONCLUSION: WH-MRA allows good coronary artery visualization in
      healthy subjects and patients and provides a simplified scanning procedure and
      advantages in 3D post-processing. Regarding image parameters and the detection of
      CAD, the results are comparable to those acquired with t-MRA. The major
      disadvantage remains the high number of diagnostically insufficient images.

PMID- 16612790
TI  - [Unusual appearance picture of intracranial extra-axial metastasis of prostatic
      carcinoma].

PMID- 16612791
TI  - [Myoepithelial carcinoma in pleomorphic adenoma -- a rarity among tumors of the
      parotid gland].

PMID- 16612792
TI  - Mechanically loaded ex vivo bone culture system 'Zetos': systems and culture
      preparation.
AB  - This paper introduces the culture preparation of ovine, bovine and human
      cancellous bone cores to be used in an explants model Zetos. The three
      dimensional (3D) bone cores were prepared and evaluated for all three animals.
      Bone cells in vivo constantly interact with each other, migratory cells,
      surrounding extracellular matrix (ECM) and interstitial fluid in a
      microenvironment, which continuously responds to various endogenous and exogenous
      stimuli. The Zetos system was designed to culture and mechanically load viable
      cancellous bone explants in their near natural microenvironment. This 3D ex vivo
      system bridges the current gap between in vitro and in vivo methods. One aim of
      this work was to compare the macro and micro-architecture of ovine, bovine and
      human cancellous bone tissue in preparation for culture within the Zetos system
      in order to determine the optimal source of experimental material. A second aim
      was to optimise the preparations of the bone cores as well as develop techniques
      involved during tissue maintenance. Bone core response was visualised using
      histological and immunohistochemical methods. The results demonstrate that
      cancellous bone explants vary greatly in trabecular density and bone volume
      depending on species, age and location. Sheep and human samples displayed the
      greatest variation between bones cores when compared to bovine. Even cores taken
      from the same animal possessed very different characteristics. The histology
      demonstrated normal bone and cell structure after the core preparation.
      Immunohistochemistry results demonstrated antigen retention after preparation
      methods.

PMID- 16612794
TI  - A proteomic approach for dissecting H-Ras signaling networks in NIH/3T3 mouse
      embryonic fibroblast cells.
AB  - To elucidate an understanding into H-Ras protein network, we have established
      various oncogene H-Ras-expressing NIH/3T3 mouse embryonic fibroblast cell clones,
      which are expressing G12V H-Ras, G12R H-Ras, and G12V/T35S H-Ras proteins under
      the tight control of expression by an antibiotic doxycycline. Here we provide a
      catalog of proteome profiles in total cell lysate derived from the oncogenic and
      partial loss of function H-Ras-expressing NIH/3T3 cells. In this biological
      context, we compared total proteome changes by the combined methods of 2-DE,
      quantitative image analysis and MALDI-TOF-MS analysis both commonly in oncogenic
      and partial loss of function H-Ras expression system. Thus, we tried to dissect H
      Ras signaling pathway, especially a downstream effector molecule, Raf in NIH/3T3
      cells using proteomics tools. In this study, we centralized upon the proteome
      profile changes as common targets for oncogenic H-Ras and a partial loss of
      function H-Ras in the H-Ras-expressing cells. Thirteen protein spots were
      selected as what the staining intensities on the gels for 2-DE images from both
      kinds of cells were consistently changed in their protein expression level.
      Differentially regulated expression was further confirmed for some subsets of
      candidates by semiquantitative RT-PCR and Western blot analysis using specific
      antibodies. Taken together, our results obtained and present here show that the
      comparative analysis of proteome from oncogenic and partial loss of function H
      Ras-expressing cells has yielded interpretable data to elucidate the protein
      network directly and/or indirectly.

PMID- 16612795
TI  - Effects of salinity levels on proteome of Suaeda aegyptiaca leaves.
AB  - Saline soils are the major problem of cultivated lands of Iran. Suaeda aegyptiaca
      is a salt-tolerant plant (halophytes) that grow naturally in salt-affected areas
      of Iran. We have employed proteomics to identify the mechanisms of salt
      responsiveness in leaves of S. aegyptiaca grown under different salt
      concentrations. Ten-day-old plants were treated with 0, 150, 300, 450, and 600 mM
      NaCl. After 30 days of treatment, leaf samples were collected and analyzed using
      2-D-PAGE. Out of 700 protein spots reproducible detected within replications, 102
      spots showed significant response to salt treatment compared to 0 mM NaCl. We
      analyzed expression pattern of salt-responsive proteins using a hierarchical and
      two nonhierarchical (Fuzzy ART and SOM) statistical methods and concluded that
      Fuzzy ART is the superior method. Forty proteins of 12 different expression
      groups were analyzed using LC/MS/MS. Of these, 27 protein spots were identified
      including proteins involved in oxidative stress tolerance, glycinebetain
      synthesis, cytoskeleton remodeling, photosynthesis, ATP production, protein
      degradation, cyanide detoxification, and chaperone activities. The expression
      pattern of these proteins and their possible roles in the adaptation of S.
      aegyptiaca to salinity is discussed.

PMID- 16612798
TI  - X-ray absorption spectroscopic study of LiCoO2 as the negative electrode of
      lithium-ion batteries.
AB  - Lithium cobalt oxide (LiCoO(2)) particles are modified using rotor blade grinding
      and re-annealing and used as the active electrode material versus lithium in the
      3-0 V potential interval, in which a maximum capacity of 903 mA h g(-1) is
      achieved. X-ray absorption near edge structure spectra reveal the complete
      reduction of Co(3+) to Co metal at 0 V. Cell recharge leads to an incomplete
      reoxidation of cobalt. A maximum reversible capacity of 812 mA h g(-1) is
      obtained, although a poor capacity retention upon prolonged cycling may limit its
      application.

PMID- 16612799
TI  - Computational study of 19F NMR spectra of double four ring-containing Si/Ge
      zeolites.
AB  - (19)F NMR chemical shifts are calculated in order to study the F(-) environment
      in double four ring (D4R) containing Si/Ge-zeolites. The calculations with the
      DFT/CSGT/B3PW91 methodology yielded an agreement within 2 ppm with respect to the
      experimental peaks corresponding to the D4R units containing 8Si0Ge, 7Si1Ge and
      0Si8Ge of the octadecasil zeolite. The optimisation of the 7Si1Ge-, 6Si2Ge-,
      5Si3Ge- and 4Si4Ge-D4R units with DFT/B3LYP methodology shows that a covalent Ge
      F bond is formed and therefore a Ge atom in the D4R is pentacoordinated. The
      displacement of the fluoride ion towards a Ge atom in the Ge-containing D4R units
      locates four Si/Ge atoms in the close vicinity of the F(-) and this makes
      possible a rationalization of the (19)F NMR signals in groups according to the
      number of Si (n) and Ge (m) atoms in the nearest F(-) environment, F-Si(n)Ge(m)
      (where n+m=4). Thus, the calculated chemical shifts show that higher values are
      observed when the number of Ge atoms in the nearest F(-) environment increases.

PMID- 16612801
TI  - Geometrical and algebraic approach to central molecular chirality: a chirality
      index and an Aufbau description of tetrahedral molecules.
AB  - On the basis of empirical Fischer projections, we develop an algebraic approach
      to the central molecular chirality of tetrahedral molecules. The elements of such
      an algebra are obtained from the 24 projections which a single chiral tetrahedron
      can generate in S and R absolute configurations. They constitute a matrix
      representation of the O4 orthogonal group. According to this representation,
      given a molecule with n chiral centres, it is possible to define an "index of
      chirality chi identical with {n, p}", where n is the number of stereogenic
      centres of the molecule and p the number of permutations observed under rotations
      and superimpositions of the tetrahedral molecule to its mirror image. The
      chirality index not only assigns the global chirality of a given tetrahedral
      chain, but indicates also a way to predict the same property for new compounds,
      which can be built up consistently.

PMID- 16612802
TI  - An attempt to determine the absolute configuration of two ascolactone
      stereoisomers with time-dependent density functional theory.
AB  - Two stereoisomers of ascolactone (A, B), natural products with two asymmetric
      carbon atoms, are isolated from the marine-derived fungus Ascochyta salicorniae.
      Although these compounds show virtually opposite CD spectra and [alpha]D, 1H- and
      13C-NMR data exclude the presence of enantiomers and suggest ascolactone A and B
      to be epimeric lactones. By comparing the experimental CD spectra with those
      calculated employing time-dependent density functional theory (TDDFT), we
      elucidate the configuration at one of the asymmetric carbon atoms.

PMID- 16612803
TI  - Theoretical insights into photochemical reactions initiated with circularly
      polarized light.
AB  - A theoretical analysis of several hypothetical photoreactions initiated with
      circularly polarized light has been carried out to determine the factors
      influencing the enantiomeric excess of recovered reactant. The anistropic g value
      is the dominant influence, although quantum yields and F values may be important
      in certain cases.

PMID- 16612804
TI  - Protein Circular Dichroism Data Bank (PCDDB): data bank and website design.
AB  - The Protein Circular Dichroism Data Bank (PCDDB) is a new deposition data bank
      for validated circular dichroism spectra of biomacromolecules. Its aim is to be a
      resource for the structural biology and bioinformatics communities, providing
      open access and archiving facilities for circular dichroism and synchrotron
      radiation circular dichroism spectra. It is named in parallel with the Protein
      Data Bank (PDB), a long-existing valuable reference data bank for protein crystal
      and NMR structures. In this article, we discuss the design of the data bank
      structure and the deposition website located at http://pcddb.cryst.bbk.ac.uk. Our
      aim is to produce a flexible and comprehensive archive, which enables user
      friendly spectral deposition and searching. In the case of a protein whose
      crystal structure and sequence are known, the PCDDB entry will be linked to the
      appropriate PDB and sequence data bank files, respectively. It is anticipated
      that the PCDDB will provide a readily accessible biophysical catalogue of
      information on folded proteins that may be of value in structural genomics
      programs, for quality control and archiving in industrial and academic labs, as a
      resource for programs developing spectroscopic structural analysis methods, and
      in bioinformatics studies.

PMID- 16612805
TI  - Spontaneous absolute asymmetric synthesis in the presence of achiral silica gel
      in conjunction with asymmetric autocatalysis.
AB  - An enantiomerically enriched pyrimidyl alkanol with either S or R configurations
      was obtained stochastically from the reaction between pyrimidine-5-carbaldehyde
      and diisopropylzinc in the presence of achiral silica gel in conjunction with
      asymmetric autocatalysis with amplification of chirality.

PMID- 16612806
TI  - 1H-MRS internal thermometry in test-objects (phantoms) to within 0.1 K for
      quality assurance in long-term quantitative MR studies.
AB  - Many magnetic resonance test-object properties are temperature-dependent, with
      typical temperature coefficients of approximately 2-3% K(-1). Therefore, to
      achieve consistent quality assurance measurements to within 1%, test object
      temperatures should ideally be known to within 0.3 K. Proton magnetic resonance
      spectroscopy has previously been used to estimate accurately absolute tissue
      temperature in vivo, based on the linear temperature dependence of the chemical
      shift difference between water and temperature-stable reference metabolites such
      as N-acetylaspartate. In this study, this method of 'internal thermometry' in
      quality assurance test-objects was investigated, and in particular the value of
      sodium 3-(trimethylsilyl)propane-1-sulfonate (DSS) as a chemical shift reference
      was demonstrated. The relationship between the DSS-water chemical shift
      difference (sigma, expressed in ppm) and temperature tau (in K) was shown to be
      tau = 764.55 (+/-5.05) - 97.72 (+/-1.05) sigma (286 <or= tau <or= 309 K).
      Internal thermometry in MRI test-objects is feasible and straightforward, using
      readily available (1)H-MRS pulse sequences and standard spectroscopy evaluation
      packages, with a minimum detectable temperature difference of 100 (+/-20) mK.

PMID- 16612807
TI  - Cathepsin B-like proteinase is involved in the decomposition of the adult fat
      body of Helicoverpa armigera.
AB  - Cathepsin B-like proteinase (HCB, EC 3.4.22.1) is expressed in Helicoverpa
      armigera oocytes and adult fat bodies. Previous work has revealed that HCB plays
      a key role in the degradation of yolk proteins during embryogenesis. This study
      investigated the function and regulatory activation of HCB in adult fat bodies
      during aging and oogenesis. The HCB transcript was detected at all stages from
      larval to adult fat bodies with Northern blot analysis. Pro-HCB was also detected
      in fat bodies at these stages with an immunoblot assay using a monoclonal
      antibody against HCB. However, mature HCB and its activity were only detected in
      fat bodies of pre-adults and adults. This evidence suggested that HCB is
      regulated post-translationally by activation of the pro-enzyme during the pupa
      adult metamorphosis. The activation of HCB was coupled with the expression of
      hormone receptor 3 (HHR3), and was up-regulated by the ecdysteroid agonist, RH
      2485, suggesting that HCB activation is related to the ecdysone regulatory
      system. The decomposition of the adult fat bodies during aging and oogenesis was
      found to occur via programmed cell death, in which HCB took part.

PMID- 16612808
TI  - Allatotropin-like peptide in Heliothis virescens: tissue localization and
      quantification.
AB  - The mating-induced increase in juvenile hormone (JH) biosynthesis in Heliothis
      virescens females may be stimulated by production and/or release of stimulatory
      neuropeptides such as allatotropins (AT). Although there is evidence that H.
      virescens allatotropin may be structurally related to Manduca sexta allatotropin
      (Manse-AT), little is known of its occurrence and distribution in H. virescens.
      An enzyme-linked immunosorbent assay (ELISA) using a monoclonal antibody against
      Manse-AT was used to quantify concentrations of Manse-AT immunoreactivity in
      tissue extracts of H. virescens. In mated females, the highest concentrations of
      Manse-AT-like material occurred in the brain. The ventral nervous system and the
      accessory glands also contained considerable amounts of Manse-AT-like material,
      whereas concentrations were very low in ovaries, fat body, and flight muscle. The
      Manse-AT antibody was used for whole-mount immunocytochemistry to localize Manse
      AT-immunoreactivity in the central nervous system. Several groups of Manse-AT
      immunoreactive cells were discovered in the brain, subesophageal ganglion, and
      thoracic and abdominal ganglia of H. virescens females and males. Strong
      immunoreactivity was detected in axons going through the corpora cardiaca and
      branching out over the surface of the corpora allata. The presence of Manse-AT
      like material in various locations in the central nervous system suggests that
      these peptides may have other as yet unknown functions. At the posterior margin
      of the terminal ganglion of males, a group of large immunoreactive cells was
      observed that was not present in females. Other than that, there were no obvious
      differences between virgin and mated females or males. The lack of differences in
      AT distribution in mated and virgin females suggests that mating-induced
      differences in female JH biosynthesis rates may be caused by changes in cellular
      response to AT at the level of the CA, rather than by changes in the amounts of
      AT acting on the CA.

PMID- 16612809
TI  - Responses of protein phosphatases and cAMP-dependent protein kinase in a freeze
      avoiding insect, Epiblema scudderiana.
AB  - Larvae of the goldenrod gall moth, Epiblema scudderiana, use the freeze avoidance
      strategy of winter cold hardiness and show multiple metabolic adaptations for
      subzero survival including accumulation of large amounts of glycerol as a
      colligative antifreeze. Induction and regulation of cold hardiness adaptations
      requires the intermediary action of signal transduction enzymes. Changes in the
      activities of several signaling enzymes including cAMP-dependent protein kinase
      (PKA), protein phosphatases 1 (PP1), 2A, 2C, and protein tyrosine phosphatases
      (PTPs) were monitored over the winter and during experimental exposures of larvae
      to subzero temperatures (-4 degrees C, a temperature that triggers rapid glycerol
      synthesis, or -20 degrees C, a common midwinter ambient temperature) or anoxia. A
      strong increase in the amount of active PP1 in the latter part of the winter may
      be responsible for shutting off glycogenolysis once glycerol levels are
      maximized. There appears to be a limited role for PKA in overwintering but PP2A
      and PP2C activities rose when larvae were exposed to -20 degrees C and PTP
      activities rose significantly over the winter months and also in response to
      laboratory subzero (-20 degrees C) and anoxia exposures. The strong responses by
      PTPs suggest that these may be involved in cell cycle and growth arrest during
      winter diapause.

PMID- 16612810
TI  - Courtship dances in the flies of the genus Lispe (Diptera: Muscidae): from the
      fly's viewpoint.
AB  - Two predatory fly species, Lispe consanguinea Loew, 1858 and L. tentaculata
      DeGeer, 1776, inhabit the supralittoral zone at the shore of a fresh-water
      reservoir. Both species look alike and possess similar "badges," reflective
      concave silvery scales on the face. Flies occupy different lek habitats. Males of
      the first species patrol the bare wet sand on the beach just above the surf.
      Males of the second species reside on the more textured heaps of algae and
      stones. Courtship and aggressive behaviour of males was video-recorded and
      analysed frame by frame. Visual stimuli provided by the conspecific partner were
      computed in the body-fixed space of a fly observer. Males of L. consanguinea
      perform long pedestrian dances of pendulating circular arcs (frequency 2 s(-1),
      median radius 2.5 cm, linear velocity 0.130 m/s). Right and left side runs are
      equally probable. Circular runs are interrupted by standby intervals of average
      duration 0.35 s. The female views the male as a target covering 2 by 2 ommatidia,
      moving abruptly with the angular velocity over 200 degrees/s in a horizontal
      direction down the path of about 50 degrees till the next standpoint. Dancing is
      evenly distributed around the female. On the contrary, the male fixates the image
      of the female within the narrow front sector (median +/-10 degrees); the target
      in his view has 6-7 times less angular velocity and angular span of oscillations,
      and its image in profile overlays 6-8 by 2 ommatidia. If the female walks, the
      male combines tracking with voluntary circular dances. Rival males circle about
      one another at a distance shorter than 15 mm, but not in close contact. Males of
      L. tentaculata are capable of similar circular courting dances, but do so rarely.
      Usually they try to mount any partner immediately. In the latter species, male
      combat consists of fierce wrestling. Flies of both species often walk sideward
      and observe the partner not in front but at the side.

PMID- 16612812
TI  - Sensitivity of Uncinula necator to quinoxyfen: evaluation of isolates selected
      using a discriminatory dose screen.
AB  - Quinoxyfen is a protectant fungicide that provides excellent control of many
      powdery mildew diseases. Prior to the launch of quinoxyfen in vines in 1998, a
      leaf disc sporulation assay was developed to assess the sensitivity of Uncinula
      necator (Schw) Burr to quinoxyfen. The distribution of EC(50) values from 56
      monoconidial U. necator isolates collected from six countries between 1993 and
      1996 was found to range from less than 0.03 to 2.6 mg litre(-1). Although this
      range of EC(50) values was quite broad, the inability to establish a minimum
      inhibitory concentration (MIC) for the majority of these isolates, including some
      of the most sensitive isolates, was unexpected and suggested that the leaf disc
      sporulation assay may not reflect the true activity of quinoxyfen in the field.
      In 2002, following the detection of isolates resistant to quinoxyfen in Blumeria
      graminis Speer f. sp. tritici Marchal, a discriminatory dose screen was developed
      to test large populations of U. necator for rare individuals with significantly
      decreased sensitivity to quinoxyfen. The individual isolates selected by this
      method were tested with the leaf disc sporulation assay. Although a significant
      proportion were found to have EC(50) values within the original distribution, a
      number of isolates with apparent reduced sensitivity to quinoxyfen were also
      detected. However, further examination of a subset of these isolates in a more
      quantitative germination/germ tube elongation inhibition assay suggested that the
      magnitude of the reduction in sensitivity for some of these isolates was much
      less than predicted by the sporulation assay. Thus, for an exclusively protectant
      fungicide such as quinoxyfen, a leaf disc sporulation assay may overestimate the
      frequency of isolates with significantly reduced sensitivity and the threat of
      decreased performance due to resistance.

PMID- 16612813
TI  - Mineralisation of atrazine, metolachlor and their respective metabolites in
      vegetated filter strip and cultivated soil.
AB  - In vegetated filter strips (VFS) the presence of perennial vegetation,
      rhizodeposition of labile organic substrates and the accumulation of an organic
      residue thatch layer may enhance microbial numbers and activity, thereby
      increasing the potential for mineralisation of herbicides and herbicide
      metabolites retained during run-off events. The objective of this laboratory
      experiment was to compare the mineralisation of atrazine and metolachlor with
      that of their respective metabolites in VFS and cultivated soil. With the
      exception of total bacteria, propagule density of the microbial groups,
      endogenous soil enzymes and microbial diversity were higher in the VFS soil. This
      correlated with increased mineralisation of metolachlor and its metabolites in
      the VFS soil and indicates potential for VFS to curtail the subsequent transport
      of these compounds. In contrast, the mineralisation of atrazine and the majority
      of its metabolites was substantially reduced in VFS soil relative to cultivated
      soil. Consequently, the potential for subsequent transport of atrazine and many
      of its metabolites may be greater in VFS soil than in cultivated soil if reduced
      mineralisation is not offset by increased sorption in the VFS.

PMID- 16612814
TI  - Panic reactions to terrorist attacks and probable posttraumatic stress disorder
      in adolescents.
AB  - A number of factors, including subjective reactions and appraisal of danger,
      influence one's reaction to a traumatic event. This study used telephone survey
      methodology to examine adolescent and parent reactions to the 2001 World Trade
      Center attacks 6 to 9 months after they occurred. The prevalence of probable
      posttraumatic stress disorder (PTSD) in adolescents was 12.6%; 26.2% met study
      criteria for probable subthreshold PTSD. A probable peri-event panic attack in
      adolescents was strongly associated with subsequent probable PTSD and probable
      subthreshold PTSD. This study suggests that the early identification of peri
      event panic attacks following mass traumatic events may provide an important
      gateway to intervention in the subsequent development of PTSD. Future studies
      should use longitudinal designs to examine the course and pathogenic pathways for
      the development of panic, PTSD, and other anxiety disorders after exposure to
      disasters.

PMID- 16612815
TI  - Differential relationships of childhood abuse and neglect subtypes to PTSD
      symptom clusters among adolescent inpatients.
AB  - This article investigates whether childhood abuse and neglect subtypes (i.e.,
      physical, sexual, and emotional abuse, and physical and emotional neglect)
      differentially predict the severity of individual posttraumatic stress disorder
      (PTSD) symptom clusters and overall posttraumatic stress. Eighty-nine patients
      admitted to the short-term adolescent treatment unit of a psychiatric hospital
      completed a battery of psychological assessments. Findings of multiple regression
      analyses showed that emotional and sexual abuse rather than physical abuse,
      emotional neglect, or physical neglect is related to individual symptom cluster
      severity and overall posttraumatic stress. Results suggested that a greater level
      of specificity is necessary when assessing child abuse and posttraumatic stress
      because each level provides more specific information about how to intervene to
      reduce the risk of negative outcomes.

PMID- 16612816
TI  - Validation of the multiple language versions of the Reactions of Adolescents to
      Traumatic Stress questionnaire.
AB  - The objective of this study was to assess the preliminary psychometric properties
      of the Reaction of Adolescents to Traumatic Stress questionnaire (RATS) for
      refugee adolescents. Four independent heterogeneous adolescent population samples
      (N = 3,535) of unaccompanied refugee minors, immigrants, and native Dutch and
      Belgian adolescents were assessed at school. The confirmatory factor analyses,
      per language version, support the three-factor structure of intrusion,
      avoidance/numbing, and hyperarsoual. The total and subscales of the RATS show
      good internal consistency and good (content, construct, and criterion) validity.
      The RATS, in this study, was found to be a reliable and valid instrument for
      assessing posttraumatic stress reactions of culturally diverse adolescents.

PMID- 16612817
TI  - Effect of reinforcement particle size on in vitro behavior of beta-tricalcium
      phosphate-reinforced high-density polyethylene: a novel orthopedic composite.
AB  - Beta-tricalcium phosphate-reinforced high-density polyethylene (beta-TCP/HDPE) is
      a new biomaterial, which was made to simulate bone composition and study its
      capacity to act like bony tissues. This material was produced by replacing
      mineral component and collagen soft tissue of bone with beta-TCP and HDPE,
      respectively. The biocompatibility of composite samples with different volume
      fractions of TCP (20, 30, and 40 vol %) and two different particle sizes (80-100
      and 120-140 mesh size) was examined in vitro using the osteoblast cell line G-292
      by proliferation, alkaline phosphatase (ALP) production, and cell adhesion
      assays. Cell-material interaction on the surface of the composites was observed
      by scanning electron microscopy (SEM). The effect of beta-TCP particle size on
      behavior of the osteoblast cell line was compared between two groups of the
      composite samples containing smaller and larger reinforcement particle sizes as
      well as with those of a negative control. In general, results showed that the
      composite samples containing larger particles supported a higher rate of
      proliferation and ALP production by osteoblast cells after 3, 7, and 14 days of
      incubation compared to the composite samples with smaller particle size and
      control. Furthermore, more cells were attached to the surface of composite
      samples containing larger particle size when compared to the smaller particle
      size composites (p<0.05). This number was nearly equal with numbers adhered on
      negative control [tissue culture polystyrene (TPS)] and significantly higher in
      comparison with composite control [polyethylene (PE)] (p<0.05). Adhered cells
      presented a normal morphology by SEM and many of the cells were seen to be
      undergoing cell division. These findings indicate that beta-TCP/HDPE composites
      are biocompatible, nontoxic, and in some cases, act to stimulate proliferation of
      the cells, ALP production, and cell adhesion when compared to the control
      counterparts. Furthermore, beta-TCP/HDPE samples with larger reinforcement
      particle size were shown to possess better biological properties.

PMID- 16612818
TI  - Special section: innovations in trauma research methods.

PMID- 16612819
TI  - Disaster research methods: past progress and future directions.
AB  - Published results for 225 disaster studies were coded on methodological
      variables, severity of effects, and event year. Methods varied greatly, but cross
      sectional, after-only designs, convenience sampling, and small samples were
      modal. Samples that were assessed before the disaster, selected for reasons of
      convenience, or were large tended to show less severe effects than other samples.
      Developing countries were underrepresented overall, but not in recent years.
      Certain desirable study characteristics (longitudinal designs, representative
      samples) have been decreasing in prevalence over time, whereas others (early
      first assessment) have been increasing. Innovations such as latent trajectory
      modeling or hierarchical linear modeling might advance the field's ability to
      capture the complexity of disasters, but the field still needs to attend to the
      fundamentals of sound epidemiologic research.

PMID- 16612820
TI  - Web-based methods in terrorism and disaster research.
AB  - This article provides an overview of the use of the Internet for conducting
      studies after terrorist attacks and other large-scale disasters. We begin with a
      brief summary of the scientific and logistical challenges of conducting such
      research, followed by a description of some of the most important design features
      that are required to produce valid findings. We then describe one approach to
      Internet surveys that, although not perfect, addresses many of the challenges
      well. We close with some thoughts about how the Internet-based methods available
      today are likely to develop further in coming years.

PMID- 16612821
TI  - Domestic violence exposure in Colombian adolescents: pathways to violent and
      prosocial behavior.
AB  - Associations between domestic violence exposure and violent and prosocial
      behavior were tested in a sample of Colombian adolescents, with attention to
      impulsivity and substance use problems as mediators of these associations. A
      representative sample of 1,152 school youths and a convenience group of 148
      juvenile offenders aged 11-19 years participated. Results using structural
      equation modeling showed indirect effects of impulsivity and substance use
      problems between family violence (i.e., exposure to interparental violence) and
      violent behavior. Maltreatment (i.e., harsh parenting) was directly associated
      with violent behavior, though impulsivity and substance use problems also
      mediated this relation. Maltreatment directly and inversely contributed to
      prosocial behavior but there was no evidence of mediation. Results are discussed
      in terms of cognitive and behavioral factors that explain violent and prosocial
      behavior among Colombian youths. Limitations and implications for prevention are
      described.

PMID- 16612822
TI  - Child sexual abuse and posttraumatic stress disorder: the role of age at first
      use of substances and lifetime traumatic events.
AB  - This study explores cross-sectional relationships among childhood sexual abuse
      (CSA), lifetime traumatic events (LTEs), age at first use of substances, and
      posttraumatic stress disorder (PTSD) in 644 low-income substance abusing women.
      History of CSA covaried with earlier age at substance use and higher reported
      rates of LTEs. Association between first use and LTEs was inconclusive. Both CSA
      and LTEs predicted PTSD with a partial mediation effect by LTEs. However, first
      use did not mediate the relationship between CSA and LTEs, rather, CSA directly
      contributed to increased rates of LTEs.

PMID- 16612823
TI  - Sexual and physical abuse among Korean female inpatients with schizophrenia.
AB  - The study reports the prevalence and correlates of sexual and physical abuse in a
      sample of 100 female inpatients with schizophrenia in South Korea. Clinical
      assessment interviews consisted of the Positive and Negative Syndrome Scale, the
      Scale for the Assessment of Positive Symptoms, an interview assessing history of
      sexual and repeated physical abuse, and demographic and psychosocial factors.
      Lifetime prevalence of severe sexual or physical abuse was 52%. Compared with
      nonabused patients (n = 48), the abused patients (n = 52) showed more
      nonpsychotic symptoms (i.e., anxiety, depression) and higher levels of distress,
      but no difference in psychotic symptoms. This study failed to note significant
      differences in positive symptoms addressed in previous Western studies.

PMID- 16612824
TI  - Posttraumatic stress in aging World War II survivors after a fireworks disaster:
      a controlled prospective study.
AB  - Little is known about the effects of cumulative trauma and whether traumatized
      individuals are more vulnerable. In 2000, a fireworks disaster created the
      possibility to examine this issue among World War II survivors who were part of
      an ongoing longitudinal study. Between 1998 and 2000 posttraumatic stress
      increased in disaster exposed respondents as opposed to the control group. War
      related reexperiencing and avoidance also increased. The strongest increase
      occurred in disaster-exposed respondents who had low levels of wartime stress and
      a slight decrease occurred in those who had high wartime exposure. This unique
      controlled observation suggests that disasters do increase the levels of
      posttraumatic stress, and that reactivation of previous traumatic events
      generally occurs. However, the vulnerability hypothesis was not supported.

PMID- 16612825
TI  - Posttraumatic stress in children with first responders in their families.
AB  - High levels of exposure and occupational stress of first responders may have
      caused children in first-responder families to become traumatized following the
      September 11th, 2001 terrorist attacks. New York City public school children (N =
      8,236) participated in a study examining mental health problems 6 months after
      the World Trade Center attack. Results revealed that children with emergency
      medical technician (EMT) family members had a high prevalence of probable
      posttraumatic stress disorder (PTSD; 18.9%). Differences in rates of probable
      PTSD among EMTs' and firefighters' children were explained by demographic
      characteristics. Where EMTs are drawn from disadvantaged groups, one implication
      of this study is to target EMT families in any mental health interventions for
      children of first responders.

PMID- 16612826
TI  - Predictors of responses to psychotherapy referral of WTC utility disaster
      workers.
AB  - This study examined male utility disaster workers' responses to referral for
      trauma-specific psychotherapy. Among 328 workers offered referral for symptoms
      related to the World Trade Center (WTC) attacks during psychological screening,
      approximately 48% chose to accept, 28% chose to consider only, and 24% chose to
      decline. Analyses examined predisposing factors, i.e., age, race/ethnicity,
      marital status, education, previous mental health treatment, and previous
      disorder; as well as illness level; i.e., posttraumatic stress disorder (PTSD),
      depression, and general psychiatric distress; current treatment; and time of
      referral as predictors of referral response. PTSD (specifically reexperiencing
      and hyperarousal symptoms), depressive symptoms, and previous mental health
      treatment were positively associated with workers' accepting referral.
      Implications and limitations of these findings are discussed.

PMID- 16612827
TI  - Characterizing time in longitudinal trauma research.
AB  - Despite the proliferation of longitudinal trauma research, careful attention to
      timing of assessments is often lacking. Patterns in timing of assessments,
      alternative time structures, and the treatment of time as an outcome are
      discussed and illustrated using trauma data.

PMID- 16612828
TI  - Measuring and modeling the social and geographic context of trauma: a multilevel
      modeling approach.
AB  - Increasingly it is recognized that health and illness are products of individual
      level risk and protective factors, as well as forces operating at contextual
      levels. In this article, we present the motivation and rationale for
      understanding trauma within its context. We use the example of the concept of
      social capital to illustrate the relevance of the contextual approach for trauma
      research and outline a multilevel modeling approach to examining contextual
      influences on trauma outcomes.

PMID- 16612829
TI  - Interlobular excretory ducts of mammalian salivary glands: structural and
      histochemical review.
AB  - In the major salivary glands of mammals, excretory ducts (EDs) succeed striated
      ducts. They are for the most part interlobular in position, although their
      proximal portions sometimes are on the periphery of a lobule, where they
      occasionally retain some of the structural features of striated ducts. Based on a
      survey of a broad range of mammalian species and glands, the predominant tissue
      type that composes EDs is pseudostratified epithelium. In some species, there is
      a progression of epithelial types: the proximal EDs are composed of simple
      cuboidal or columnar epithelium that, in the excurrent direction, usually gives
      way to the pseudostratified variety. Secretory granules are visible in the apical
      cytoplasm of the principal cells of the EDs of only a few species, but
      histochemistry has shown the presence of a variety of glycoproteins in these
      cells in a spectrum of species. Moreover, the latter methodology has revealed the
      presence of a variety of oxidative, acid hydrolytic, and transport enzymes in the
      EDs, showing that, rather than simply acting as a conduit for saliva, these ducts
      play a metabolically active role in gland function. It is difficult to describe a
      "typical" mammalian ED because it can vary along its length and interspecific
      variation does not follow a phylogenetic pattern. Moreover, in contrast to
      intercalated and striated ducts, ED cellular features do not exhibit a
      relationship to diet.

PMID- 16612830
TI  - Tissue distribution of basigin and monocarboxylate transporter 1 in the adult
      male mouse: a study using the wild-type and basigin gene knockout mice.
AB  - Basigin (Bsg) is a transmembrane protein that is responsible for targeting of
      monocarboxylate transporters (MCTs) to the cell membrane. The present study was
      conducted to determine whether or not Bsg was required for the proper
      localization of MCT isoform 1 (MCT1) in a wide range of tissues in adult male
      mice. The tissue distributions of Bsg and MCT1 in wild-type (WT) mice, the tissue
      distribution of MCT1 in Bsg gene knockout (Bsg-KO) mice, and the protein and mRNA
      levels of MCT1 in both genotypes were studied. Immunohistochemistry demonstrated
      that Bsg colocalized with MCT1 in the cerebrum, retina, skeletal and cardiac
      muscle, duodenal epithelium, hepatic sinusoid, proximal uriniferous tubules,
      Leydig cells, and efferent ductule epithelium in WT mice. Bsg was absent but MCT1
      was present in Sertoli cells, cauda epididymis, myoepithelial cells and duct of
      the mandibular gland, surface epithelium of the stomach and bronchioles. In Bsg
      KO mice, with the exception of Leydig cells, MCT1 immunostaining was greatly
      reduced in intensity and its distribution was altered in tissues that expressed
      both Bsg and MCT1 in WT mice. Levels of the protein and mRNA for MCT1 in these
      tissues did not change significantly in Bsg-KO mice. On the other hand,
      immunostaining patterns in cells in which Bsg was absent but MCT1 was present in
      WT mice remained unchanged in Bsg-KO mice. These observations suggest that Bsg is
      required for the proper localization of MCT1 in a wide range of cells but not in
      every cell type.

PMID- 16612831
TI  - Comparative analysis of neuroectodermal differentiation capacity of human bone
      marrow stromal cells using various conversion protocols.
AB  - Human adult bone marrow-derived mesodermal stromal cells (hMSCs) are able to
      differentiate into multiple mesodermal tissues, including bone and cartilage.
      There is evidence that these cells are able to break germ layer commitment and
      differentiate into cells expressing neuroectodermal properties. There is still
      debate about whether this results from cell fusion, aberrant marker gene
      expression or real neuroectodermal differentiation. Here we extend our work on
      neuroectodermal conversion of adult hMSCs in vitro by evaluating various
      epigenetic conversion protocols using quantitative RT-PCR and
      immunocytochemistry. Undifferentiated hMSCs expressed high levels of fibronectin
      as well as several neuroectodermal genes commonly used to characterize neural
      cell types, such as nestin, beta-tubulin III, and GFAP, suggesting that hMSCs
      retain the ability to differentiate into neuroectodermal cell types. Protocols
      using a direct differentiation of hMSCs into a neural phenotype failed to induce
      significant changes in morphology and/or expression of markers of early and
      mature glial/neuronal cells types. In contrast, a multistep protocol with
      conversion of hMSCs into a neural stem cell-like population and subsequent
      terminal differentiation in mature glia and neurons generated relevant
      morphological changes as well as significant increase of expression levels of
      marker genes for early and late neural cell types, such as nestin, neurogenin2,
      MBP, and MAP2ab, accompanied by a loss of their mesenchymal properties. Our data
      provide an impetus for differentiating hMSCs in vitro into mature neuroectodermal
      cells. Neuroectodermally converted hMSCs may therefore ultimately help in
      treating acute and chronic neurodegenerative diseases. Analysis of marker gene
      expression for characterization of neural cells derived from MSCs has to take
      into account that several early and late neuroectodermal genes are already
      expressed in undifferentiated MSCs.

PMID- 16612832
TI  - Long-lasting coexpression of nestin and glial fibrillary acidic protein in
      primary cultures of astroglial cells with a major participation of
      nestin(+)/GFAP(-) cells in cell proliferation.
AB  - Nestin, a currently used marker of neural stem cells, is transiently coexpressed
      with glial fibrillary acidic protein (GFAP) during development and is induced in
      reactive astrocytes following brain injury. Nestin expression has also been found
      in cultures of astroglial cells, but little is known about the fate and the
      mitotic activity of nestin-expressing cells in this in vitro model. The present
      study reveals a long-lasting expression of nestin in primary cultures of
      astroglial cells derived from the rat brain. Over 70% of the cells were nestin(+)
      at 12 weeks, with a large majority coexpressing the GFAP astrocytic marker. Time
      course analyses supported a transition from a nestin(+)/GFAP(-) to a
      nestin(+)/GFAP(+) phenotype over time, which was further increased by cell cycle
      arrest. Interestingly, double staining with Ki67 revealed that over 90% of
      cycling cells were nestin(+) whereas only 28% were GFAP(+) in a population
      consisting of almost equivalent numbers of nestin(+) and GFAP(+) cells. These
      observations indicated that nestin(+)/GFAP(-) cells are actively engaged in
      mitotic activity, even after 2 weeks in vitro. Part of these cells might have
      retained properties of neural stem cells, insofar as 10% of cells in a primary
      culture of glial cells were able to generate neurospheres that gave rise to both
      neurons and astrocytes. Further studies will be necessary to characterize fully
      the proliferating cells in primary cultures of glial cells, but our present
      results reveal a major contribution of the nestin(+)/GFAP(-) cells to the
      increase in the number of astrocytes, even though nestin(+)/GFAP(+) cells
      proliferate also.

PMID- 16612833
TI  - Unconjugated bilirubin activates and damages microglia.
AB  - Microglia are the resident immune cells of the brain and are the principal source
      of cytokines produced during central nervous system inflammation. We have
      previously shown that increased levels of unconjugated bilirubin (UCB), which can
      be detrimental to the central nervous system during neonatal life, induce the
      secretion of inflammatory cytokines and glutamate by astrocytes. Nevertheless,
      the effect of UCB on microglia has never been investigated. Hence, the main goal
      of the present study was to evaluate whether UCB leads to microglial activation
      and to the release of the cytokines tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta, and IL-6. Additionally, we investigated the effects of
      UCB on glutamate efflux and cell death. The results showed that UCB induces
      morphological changes characteristic of activated microglia and the release of
      high levels of TNF-alpha, IL-1beta, and IL-6 in a concentration-dependent manner.
      In addition, UCB triggered extracellular accumulation of glutamate and an
      increased cell death by apoptosis and necrosis. These results demonstrate, for
      the first time, that UCB is toxic to microglial cells and point to microglia as
      an important target of UCB in the central nervous system. Moreover, they suggest
      that UCB-induced cytokine production, by mediating cell injury, can further
      contribute to exacerbate neurototoxicity. Interestingly, microglia cells are much
      more responsive to UCB than astrocytes. Collectively, these data indicate that
      microglia may play an important role in the pathogenesis of encephalopathy during
      severe hyperbilirubinemia.

PMID- 16612834
TI  - Measurement of inter-rater agreement for transient events using Monte Carlo
      sampled permutations.
AB  - In this paper we demonstrate the adverse effect of serially observed data
      sequences containing transient events on the calculation of Cohen's kappa as an
      index of inter-rater agreement in the detection of these events. We develop and
      use a Monte-Carlo-based permutation technique to produce an empiric distribution
      of kappa in the presence of serial dependence. We find that the empiric
      confidence intervals for kappa tend to be wider than parametrically derived
      intervals and in the case of longer event lengths, are markedly so. We evaluate
      the effect of number and length of events, and further, describe and evaluate
      three permutation methods which match specific rating situations. Finally, we
      apply these techniques to the measurement of inter-rater agreement for sleep
      disordered breathing events, a transient event identified during nocturnal
      polysomnography, for which traditionally computed confidence intervals for kappa
      are incorrect.

PMID- 16612835
TI  - A note on parameter estimation for variant Creutzfeldt-Jakob disease epidemic
      models.
AB  - A recent series of papers has raised issues regarding estimation of the key
      epidemiological parameters of variant Creutzfeldt-Jakob disease (vCJD) from
      fitting survival models to case data. In particular, it was stated that the scale
      of the epidemic cannot be estimated and must be fixed in any analysis. We show
      that this problem is an artefact of the approximate likelihood used in these
      papers to facilitate model-fitting, and is not a concern if estimation is based
      on the full likelihood. We also address comments in these papers regarding the
      choice of incubation period distribution.

PMID- 16612836
TI  - Comparison of validity of assessment methods using indices of adjusted agreement.
AB  - For comparing the validity of rating methods, the adjusted kappa (S coefficient)
      and Yule's Y index are better than Cohen's kappa which is affected by marginal
      probabilities. We consider a validity study in which a subject is assessed as
      exposed or not-exposed by two competing rating methods and the gold standard. We
      are interested in one of the methods, which is closer in agreement with the gold
      standard. We present statistical methods taking correlations into account for
      comparing the validity of the rating methods using S coefficient and Y index. We
      show how the S coefficient and Yule's Y index are related to sensitivity and
      specificity. In comparing the two rating methods, the preference is clear when
      the inference is the same for both S and Y. If the inference using S differs from
      that using Y, then it is not obvious how to decide a preference. This may occur
      when one rating method is better than the other in sensitivity but not in
      specificity. Numerical examples for comparing asbestos-exposure assessment
      methods are illustrated.

PMID- 16612837
TI  - Using trajectories from a bivariate growth curve as predictors in a Cox
      regression model.
AB  - An important research objective in most psychiatric clinical trials of
      maintenance treatment is to find predictors of recurrence of illness. In those
      trials, patients are first admitted into an open treatment period also called
      acute treatment. If they respond to the treatment and are considered to have
      stable remission from the illness, they enter the second phase of the trial where
      they are randomized into different arms of the 'maintenance treatments'. Often,
      more than one response variable is measured longitudinally in the acute treatment
      phase to monitor treatment responses. Trajectories of these response measures are
      believed to have predictive ability for recurrences in the maintenance phase of
      the trial. By using a bivariate growth curve from two such longitudinal measures,
      we developed a method to use the estimated trajectories of each subject in a Cox
      regression model to predict recurrence in the maintenance phase. To adjust for
      the parameter estimation errors, we applied a full likelihood approach based on
      the conditional expectations of the predictors. Simulation studies indicate that
      the estimation error corrected estimators for the Cox model parameters are less
      biased when compared to the naive regression estimators without accounting for
      these errors. The uniqueness of this method lies in estimating trajectories from
      bivariate unequally spaced longitudinal response measures. An illustrative
      example is provided with data from a maintenance treatment trial for major
      depression in an elderly population. Visual Fortran 90 programs were developed to
      implement the algorithm.

PMID- 16612838
TI  - Capsaicin and glucose absorption and utilization in healthy human subjects.
AB  - Although many animal experiments (under different experimental circumstances)
      have been performed, however, to date there have been no human studies of the
      role of capsaicin-sensitive afferent nerves in carbohydrate metabolism. The
      glucose loading test (administration of 75 g orally given glucose) was evaluated
      in 14 human healthy subjects by the simultaneous measurement of plasma level of
      glucose, C-peptide and glucagon every 15 min for 4 h without and with (ED50) oral
      application of capsaicin. The plasma level of glucose increased significantly
      from 30 to 150 min, and the plasma glucagon level increased from 90 to 180 min
      after the glucose loading when capsaicin administered. The plasma levels of
      insulin and C-peptide increased from 90 to 165 min after glucose loading but
      there were no significant difference between the results obtained without and
      with capsaicin administration. It is concluded that the capsaicin increases the
      glucose absorption from the gastrointestinal tract and increases the glucagon
      release (independently of the hormonal antagonist regulation by insulin released
      after glucose) loading during glucose loading tests carried out in human healthy
      subjects.

PMID- 16612839
TI  - Effects of mutations at conserved TM II residues on ligand binding and activation
      of mouse 5-HT6 receptor.
AB  - An aspartate residue (Asp-72) in the transmembrane helix II of mouse 5
      hydroxytryptamine-6 receptor (5-HT6) is conserved among most G protein-coupled
      receptors. We have examined the functional significance of this residue by site
      directed mutagenesis. A single Asp --> Ala (D72A) mutation resulted in an 8-fold
      decrease in apparent affinity for 5-HT, and a 60-fold reduction in EC50 value of
      agonist-induced stimulation of adenylyl cyclase. A F69L/T70I/D72A triple mutant
      showed a 2-fold reduction in apparent affinity for 5-HT but complete loss of
      adenylyl cyclase stimulation. Binding of SB-258585 (4-iodo-N-[4-methoxy-3-(4
      methylpiperazin-1-yl)phenyl]benzene-sulfonamide), a selective 5-HT6 antagonist,
      was mildly affected (2- to 4-fold decrease in affinity) in the two mutants. Our
      data suggest that Asp-72 and additional residues toward the intracellular side of
      TM II have a limited role in ligand binding but are critical for functional
      activation of the 5-HT6 receptor.

PMID- 16612840
TI  - The effect of ketamine on intraspinal acetylcholine release: involvement of
      spinal nicotinic receptors.
AB  - The general anaesthetic ketamine affects the central cholinergic system in
      several manners, but its effect on spinal acetylcholine release, which may be an
      important transmitter in spinal antinociception, is unknown. This study aimed to
      investigate the effect of ketamine on spinal acetylcholine release. Microdialysis
      probes were placed intraspinally in male rats, and acetylcholine was quantified
      with HPLC. Anaesthesia was switched from isoflurane (1.3%) to ketamine (150 mg/kg
      h), which resulted in a 500% increased acetylcholine release. The increase was
      attenuated during nicotinic receptor blockade (50 microM mecamylamine). The
      nicotinic receptor agonist epibatidine (175 microM) produced a ten-fold higher
      relative increase of acetylcholine release during isoflurane anaesthesia compared
      to ketamine anaesthesia (270% to 27%). Intraspinal administration of ketamine and
      norketamine both increased the acetylcholine release in high concentrations (100
      microM to 10 mM). The results indicate that spinal nicotinic receptors are
      important for the ketamine-induced acetylcholine release, and that the effect is
      partly mediated at the spinal level.

PMID- 16612841
TI  - Ascorbate elevates perfusion pressure in the bovine extraocular long posterior
      ciliary artery: role of endothelium-derived hyperpolarizing factor (EDHF).
AB  - Ascorbate blocks agonist-induced, endothelium-derived hyperpolarizing factor
      (EDHF)-mediated vasodilatation in the bovine perfused ciliary artery and this is
      associated with a rise in perfusion pressure. We now report the origins of this
      ascorbate-induced rise in perfusion pressure. In segments of ciliary artery
      perfused at 2.5 ml/min, the addition of ascorbate (10-150 microM) enhanced U46619
      induced perfusion pressure. Ascorbate produced no enhancement in the absence of
      U46619, suggesting that its effects resulted not from a constrictor action but
      through removal of a tonic vasodilator influence. Experiments revealed the
      endothelial source of this vasodilator influence, and EDHF, but not nitric oxide
      or prostanoids, appeared to be involved. The ascorbate-induced enhancement of
      vasoconstrictor tone was not seen in a static myograph or in segments perfused at
      low rates of flow, but was seen at flow rates of 2.5 ml(-1) and above. We
      conclude that ascorbate augments vasoconstrictor tone through inhibition of flow
      induced EDHF activity.

PMID- 16612842
TI  - Different effects of optical isomers of the 5-HT1A receptor antagonist
      pyrapyridolol against postischemic guinea-pig myocardial dysfunction and
      apoptosis through the mitochondrial permeability transition pore.
AB  - The recovery (%) of the left ventricular developed pressure by (S)-(-)
      pyrapyridolol (5 x 10(-8) M) (90.7%), an optical isomer of a new 5-HT1A receptor
      antagonist, was greater than that by (R)-(+)-pyrapyridolol (66.2%, control:
      34.4%) against ischemia-reperfusion injury in perfused Langendorff guinea-pig
      hearts. In the perfused mitochondrial preparation, (S)-(-)-pyrapyridolol
      inhibited the mitochondrial Ca2+ (Cam) elevation that was brought about by the
      change of Ca2+ content or pH of perfusate, similar to findings with cyclosporin
      A, well known to be an inhibitor of the mitochondrial permeability transition
      pore (MPTP). The mitochondrial K(ATP) channel opener, diazoxide, also inhibited
      the Cam elevation, but the mitochondrial K(ATP) channel antagonist, 5
      hydroxydecanoic acid, attenuated it. There were significantly fewer numbers of
      TUNEL-positive cells in these (S)-(-)-pyrapyridolol-treated hearts than the
      control or (R)-(+)-pyrapyridolol, with decreases of the caspase-3 activity.
      Therefore, these results suggest that (S)-(-)-pyrapyridolol likely inhibits the
      opening of the MPTP by preventing the Cam overload induced apoptosis related to
      endogenous 5-HT accumulation in ischemia-reperfusion hearts.

PMID- 16612843
TI  - Contribution of endothelin receptors and cyclooxygenase-derivatives to the
      altered response of the rabbit renal artery to endothelin-1 in diabetes.
AB  - The influence of diabetes on regulatory mechanisms and specific receptors
      implicated in the response of isolated rabbit renal artery to endothelin-1 was
      examined. Endothelin-1 induced a concentration-dependent contraction that was
      less potent in arteries from diabetic rabbits than in arteries from control
      rabbits. Endothelium removal or N(G)-nitro-L-arginine (L-NOARG) enhanced
      contractions to endothelin-1 either in control and diabetic arteries.
      Indomethacin inhibited endothelin-1-induced response in control arteries, but
      enhanced it in diabetic arteries. In contrast to that observed in rubbed and in L
      NOARG treated arteries, in the presence of indomethacin the contractile action of
      endothelin-1 was higher in diabetic arteries than in control arteries. Nimesulide
      enhanced endothelin-1 contractions both in control and diabetic arteries. Cyclo
      (D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123, endothelin ET(A) receptor antagonist),
      attenuated endothelin-1 vasoconstriction in control rabbits, while
      vasoconstriction resulted increased in diabetic rabbits. 2,6
      Dimethylpiperidinecarbonyl-gamma-Methyl-Leu-N(in)-(Methoxycarbonyl)-D-Trp-D-Nle
      (BQ-788, endothelin ET(B) receptor antagonist), enhanced the contractile response
      in control rabbit arteries without modifying this response in diabetic rabbits.
      In summary, diabetes decreases the sensitivity of the rabbit renal artery to
      endothelin-1 by decreasing the ratio between vasoconstrictor and vasodilator
      prostanoids released after activation of endothelin ET(A) receptors.

PMID- 16612844
TI  - Melatonin effect on endothelial cells reduces vascular permeability increase
      induced by leukotriene B4.
AB  - The aim of this study was to investigate the effect of melatonin on the
      inflammatory increase in vascular permeability. Vascular permeability was
      stimulated by a nonspecific pro-inflammatory agent (carrageenan), by drugs that
      disrupt endothelial cells junction (histamine, serotonin or bradykinin) or drugs
      that promote neutrophil recruitment (leukotriene B4 or N-formyl-methionyl-leucyl
      phenylalanine fMLP). Vascular permeability was measured by Evan's blue dye
      extravasation after simultaneous injection of melatonin and the pro-inflammatory
      drugs in rat dorsal skin. Melatonin only reduced the increase in vascular
      permeability induced by leukotriene B4, which activates both neutrophil and
      endothelial cells. The neutrophil expression of CD18 induced by leukotriene B4 or
      fMLP was not changed by melatonin. On the other hand, melatonin inhibited the
      leukotriene B4-induced endothelial cells hyperadhesiveness. Our findings suggest
      that vascular permeability reduction induced by local melatonin injection is
      mediated by a reduction of endothelial cells ability to interact with
      neutrophils.

PMID- 16612845
TI  - [Most people have to understand that accidents happen!][Interview by Ulrike
      Rostan].

PMID- 16612846
TI  - [Buprenorphine matrix patch well tolerated. The challenge of tumor pain].

PMID- 16612847
TI  - [Up-to-date indications for surgery in pleural and pulmonary tuberculosis].
AB  - Tuberculosis is an "old disease" but still remains a threat in modern days life.
      Despite human and material efforts, despite the improvements in drug therapy, the
      treatment of tuberculosis continue to consume a great amount of health care
      worldwide. A certain percentage among the patients with pleuro-pulmonary
      tuberculosis represents failures of DOTS therapy. Among them, paraclinical
      investigations will select candidates eligible for thoracic surgery. In our study
      we are reviewing the main surgical options and we present our experience
      regarding surgery in pleuro-pulmonary tuberculosis--what to operate and when is
      the best moment.

PMID- 16612848
TI  - [Thoracoscopic pleurodesis in malignant pleural effusions].
AB  - We performed retrospectively study on 136 thoracoscopies done in our clinic in
      the period January 2000 and December 2004. We reviewed 136 thoracoscopies, 71
      patients were male and 65 were female (mean age 58.4 years). Straw colored
      effusions were present in 78 cases (57%) and hemorrhagic in 58 cases (43%). The
      surgical procedure consist in diagnostic of thoracoscopy with drainage of pleural
      effusion, multiply pleural biopsy, pleurodesis and continuous pleural drainage.
      In our study, the talc powder (5g) was successfully as sclerosing agent. The
      primary tumor was: lung-63 (46%), breast-26 (19%), mesothelioma-21 (15.5%),
      stomach-3, ovarian-3, prostate-3, colon-2, lymphoma-1, leukemia-2, plasmocytoma-1
      and unknown primary tumor in 11 cases (8%). Adverse effects included-chest pain
      35 cases (25%), fever-20 cases (15%), empyema-6 cases (4.5%), prolonged air leak
      5 cases (4%), pulmonary infection-2 cases, acute respiratory failure-1 case,
      malignant invasion of scar-1 patient. For statistical analysis, the success of
      talc pleurodesis was defined as the absence of pleural fluid on the follow-up
      chest radiographs. Pleurodesis was successful in 125 cases (92%) of the patients
      after 1 month-follow-up. Thoracoscopic talc pleurodesis is a safe, economical and
      effective treatment for malignant pleural effusion.

PMID- 16612849
TI  - [Method for the molecular diagnosis of lipoprotein lipase genetic deficiency].
AB  - Modifications of plasma lipid profile is one of the major causes of a high
      cardiovascular risk. They can be the consequences of mutations in the gene
      encoding lipoprotein lipase (LPL), an enzyme that has an important role in the
      metabolism of plasma lipoproteins. The aim of the present study was to put into
      practice a method for detecting the Gly188Glu mutation in the LPL gene. The
      search was performed on a group of 107 patients with cardiovascular diseases
      and/or dyslipidemias. DNA investigation consisted, in a first stage, in the
      enzymatic digestion of exon 5 of the LPL gene, previously amplified by the PCR
      reaction, with the AvaII restriction endonuclease. Three of the subjects were
      further investigated by the sequencing of exon 5, in order to search for the
      presence of other mutations. We didn't detect the Gly188Glu mutation in none of
      the cases, and no other mutation in exon 5 was found in the three patients tested
      by DNA sequencing. We conclude that the amplification-restriction method can be
      used for the detection of known mutations in the LPL gene, allowing an early
      identification of the subjects with a high cardiovascular risk and the onset of
      the appropriate therapy. In order to detect mutations which don't affect the
      recognition sequence of a restriction enzyme and eventually new mutations, the
      sequencing of that gene is recommended.

PMID- 16612850
TI  - [Graphical registration of tongue in evaluation of the maxillo-mandibular
      relationship].
AB  - OBJECTIVE: The evaluation of the tongue-maxilla relationship, in interrelation
      with the maxilla-mandibular relationship, determined by the skeletal pattern or
      modified by the total dentures. MATERIAL AND METHOD: Clinical observations and
      verification of the tongue-maxilla relationship by a tongue-graphical
      registration, in edentulous patients, with Class II and Class III skeletal
      relationships, which had inappropriate dentures, both in vertical dimension of
      occlusion and maximal intercuspidation/centric relation. RESULTS: According to
      clinical observations and tongue-graphical registrations, there are obvious
      differences in the tongue-maxilla relationship, depending on the vertical and
      antero-posterior relations from every skeletal class and on the incorrect
      prosthesis; this leads to changes in denture's equilibrium, functionality,
      comfort and tolerance. CONCLUSIONS: The tongue-graphical registration can be used
      as a simple method of evaluation of the maxillo mandibular relationship,
      determined by the skeletal pattern or modified by dentures.

PMID- 16612852
TI  - Conservation of avian genetic resources: current opportunities and challenges.
      Proceedings of the 2005 Poultry Science Association's Ancillary Scientists
      Symposium. July 31, 2005. Auburn, Alabama, USA.

PMID- 16612851
TI  - [Periodontal reaction versus dental movement].
AB  - In orthodontics the relation between the force (natural or artificial) and the
      structures that must be modified or led towards a normal situation is in fact a
      complex equation would multiple aspects determined by the biological part. The
      orthodontic forces imply, both in action as in effect, all the elements of the
      dental system, meaning bones, teeth, periodontal tissue. On the other side, the
      structures of the dental system may help, limit ate, or even erase the action of
      the orthodontic forces. Our article brings into discussion the relation between
      the teeth' sustaining structures and their movements determined by the
      orthodontic forces both as a reaction to a therapeutical treatment and as their
      direct implication into the result and the stability of the orthodontic
      treatment, on a long-term.

PMID- 16612853
TI  - Reorganization of oral anticoagulant (warfarin) treatment follow-up.
AB  - OBJECTIVE: To evaluate the impact of the reorganization of oral AC treatment
      management in a primary healthcare setting in terms of quality of care and cost
      of care. The evaluated reorganization involved the adoption of an AC nurse
      service model supported by the use of information and communication technology
      for storing and handling follow-up data. DESIGN: Statistical analysis of AC
      follow-up data, personnel task distribution and resource use analysis, and survey
      of personnel experiences. SETTING: The Paloheina health station in Helsinki,
      Finland. SUBJECTS: All 122 Paloheina patients on oral AC treatment and the
      related Paloheina personnel. Also, follow-ups from two comparison health stations
      from Helsinki were used. MAIN OUTCOME MEASURES: Laboratory P-INR and follow-up
      density distributions before and after follow-up reorganization for Paloheina and
      comparison station patients, task distribution, and personnel resource use in
      treatment guideline assignment before and after reorganization and gathered
      personnel experiences. RESULTS: No statistically significant changes (Pearson's
      chi-square test, p < 0.05) were observed in P-INR distributions, considering also
      the comparison stations. Adoption of the AC nurse model resulted in a 66%/34%
      task distribution between nurses and physicians in guideline assignment.
      Personnel resource use analysis showed a cost decrease of 1.61 euros per follow
      up in guideline assignment. Users who responded to the survey were generally
      satisfied with the reorganization and its subjective impacts. CONCLUSION:
      Reorganization resulted in a potential reduction in cost of care per follow-up
      without a change in the observed quality of care in the Paloheina setting.
      Personnel generally accepted the reorganization.

PMID- 16612854
TI  - The responsible conduct of basic and clinical research. Papers from the 6th
      International Conference on Bioethics. June 3-4, 2005. Warsaw, Poland.

PMID- 16612855
TI  - [When will asthma run out of air?].

PMID- 16612856
TI  - Oral and maxillofacial surgery, University of Texas Southwestern Medical
      Center/Parkland Memorial Hospital.

PMID- 16612857
TI  - Personalized health: the integration of innovative sensing, textiles, information
      and communication technologies. Proceedings of an international workshop.
      December 13-15, 2004. Belfast, Northern Ireland.

PMID- 16612858
TI  - Forming a book club for nurses.

PMID- 16612859
TI  - International Conference on Harmonisation; Guidance on S8 Immunotoxicity Studies
      for Human Pharmaceuticals; availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled "S8 Immunotoxicity Studies for Human Pharmaceuticals." 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 recommendations on nonclinical testing
      approaches to identify compounds that have the potential to be immunotoxic and
      guidance on a weight-of-evidence decision making approach for immunotoxicity
      testing. The guidance is intended to provide recommendations on nonclinical
      testing for immunotoxicity induced by human pharmaceuticals. The guidance applies
      to unintended immunosuppression and immunoenhancement, excluding allergenicity or
      drug-specific autoimmunity.

PMID- 16612860
TI  - [Anatomy and diseases of the retroperitoneum CT].

PMID- 16612861
TI  - Abstracts of the 6th International Diabetes Federation Western Pacific Region
      Congress, Bangkok, Thailand.

PMID- 16612862
TI  - [MR examination of the urinary region].

PMID- 16612863
TI  - [Female pelvic MR imaging for technologists].

PMID- 16612864
TI  - [Law for the protection of personal data in the health service].

PMID- 16612865
TI  - [Introduction of software development kits on Windows for novice programmers
      handling CAD seminar contents].

PMID- 16612866
TI  - [Study of guidelines for the MDCT-imaging method for lung cancer screening].

PMID- 16612868
TI  - [Activities to promote medical safety (2003-2005)].

PMID- 16612867
TI  - [Chest CT image database for development of computer-aided diagnosis scheme].

PMID- 16612869
TI  - Abstracts of the American Association of Immunologists Annual Meeting, May 12-16,
      2006, Boston, Massachusetts, USA.

PMID- 16612870
TI  - [Present status of information technology in radiation safety regulation in
      Japan].

PMID- 16612871
TI  - [Diabetes--Paris 2006. Abstracts of Alfediam (French Language Association for the
      Study of Diabetes and Metabolic Diseases) and Alfediam Paramedical meeting, 7-10
      March 2006, Paris, France].

PMID- 16612872
TI  - [Abstracts of the 40th Congress of the French College of Vascular Pathology,
      Paris, France, 15-17 March 2006].

PMID- 16612873
TI  - Abstracts of the 38th Annual Meeting of the American Burn Association, April 4-7,
      2006, Las Vegas, Nevada.

PMID- 16612875
TI  - [Abstracts of the 30th Francophone Meeting of Digestive Pathology, 18-22 March
      2006, Paris, France].

PMID- 16612874
TI  - Selected clinical trials in breast cancer.

PMID- 16612876
TI  - Abstracts of the 31st Annual Meeting of the Society of Interventional Radiology,
      Toronto, Ontario, Canada, March 30-April 4, 2006.

PMID- 16612877
TI  - [French Neurology Society. List of members, 2006].

PMID- 16612878
TI  - Re: Bioethics, the Surviving Sepsis Campaign, and the industry.

PMID- 16612879
TI  - Re: Bioethics, the Surviving Sepsis Campaign, and the industry.

PMID- 16612880
TI  - Re: Bioethics, the Surviving Sepsis Campaign, and the industry.

PMID- 16612881
TI  - Re: Bioethics, the Surviving Sepsis Campaign, and the industry.

PMID- 16612882
TI  - Vital capacity.

PMID- 16612883
TI  - Introduction. Sexual conflict: a new paradigm?

PMID- 16612884
TI  - Sexual conflict over mating and fertilization: an overview.
AB  - Sexual conflict is a conflict between the evolutionary interests of individuals
      of the two sexes. The sexes can have different trait optima but this need not
      imply conflict if their optima can be attained simultaneously. Conflict requires
      an interaction between males and females (e.g. mating or parental care), such
      that the optimal outcomes for each sex cannot be achieved simultaneously. It is
      important to distinguish between battleground models, which define the parameter
      space for conflict and resolution models, which seek solutions for how conflicts
      are resolved. Overt behavioural conflict may or may not be manifest at
      resolution. Following Fisherian principles, an immediate (i.e. direct) benefit to
      a male that has a direct cost to his female partner can have an indirect benefit
      to the female via her male progeny. Female resistance to mating has been claimed
      to represent concurrence rather than conflict, due to female benefits via sons
      (males with low mating advantage are screened out by resistance). However, the
      weight of current evidence (both theoretical and empirical) supports sexual
      conflict for many cases. I review (i) conflicts over mate quality, encounters
      between males and females of genetically diverged subpopulations, mating rate and
      inbreeding, (ii) the special features of postcopulatory sexual conflict and (iii)
      some general features of importance for conflict resolution.

PMID- 16612885
TI  - Rapid evolution of reproductive proteins in abalone and Drosophila.
AB  - Observations from different taxa, including plants, protozoa, insects and
      mammals, indicate that proteins involved in reproduction evolve rapidly. Several
      models of adaptive evolution have been proposed to explain this phenomenon, such
      as sexual conflict, sexual selection, self versus non-self recognition and
      pathogen resistance. Here we discuss the potential role of sexual conflict in the
      rapid evolution of reproductive genes in two different animal systems, abalone
      (Haliotis) and Drosophila. In abalone, we reveal how specific interacting sperm
      egg proteins were identified and discuss this identification in the light of
      models for rapid protein evolution and speciation. For Drosophila, we describe
      the genomic approaches taken to identify male accessory gland proteins and female
      reproductive tract proteins. Patterns of protein evolution from both abalone and
      Drosophila support the predicted patterns of rapid protein evolution driven by
      sexual conflict. We stress however that other selective pressures may contribute
      to the rapid evolution that is observed. We conclude that the key to
      distinguishing between sexual conflict and other mechanisms of protein evolution
      will be an integration of genetic, experimental and theoretical data.

PMID- 16612886
TI  - Trauma, disease and collateral damage: conflict in cimicids.
AB  - The bed bugs and bat bugs (Hemiptera: Cimicidae) are unusual in being a
      gonochorist (separate male and female genders) taxon with obligate traumatic
      insemination. Males of all the species in this family have a lanceolate paramere
      (intromittent organ) which they use to pierce the female's body wall and
      inseminate directly into her haemocoel, despite the presence of a functional
      female genital tract. Mating is tightly linked to the feeding cycle in Cimex
      lectularius, the common bed bug. In this paper, I examine key aspects of the
      reproductive anatomy and behaviour of C. lectularius that underpin the nature of
      the conflict over mating rate in this species. I then examine the consequences of
      traumatic insemination for female fitness and examine potential mechanisms that
      might underpin those costs. Finally, the collateral consequences of the male
      reproductive tactic on other males of C. lectularius and the African bat bug,
      Afrocimex constrictus are examined.

PMID- 16612887
TI  - Detecting sexual conflict and sexually antagonistic coevolution.
AB  - We begin by providing an operational definition of sexual conflict that applies
      to both inter- and intralocus conflict. Using this definition, we examine a
      series of simple coevolutionary models to elucidate fruitful approaches for
      detecting interlocus sexual conflict and resultant sexually antagonistic
      coevolution. We then use published empirical examples to illustrate the utility
      of these approaches. Three relevant attributes emerge. First, the dynamics of
      sexually antagonistic coevolution may obscure the conflict itself. Second,
      competing models of inter-sexual coevolution may yield similar population
      patterns near equilibria. Third, a variety of evolutionary forces underlying
      competing models may be acting simultaneously near equilibria. One main
      conclusion is that studies of emergent patterns in extant populations (e.g.
      studies of population and/or female fitness) are unlikely to allow us to
      distinguish among competing coevolutionary models. Instead, we need more research
      aimed at identifying the forces of selection acting on shared traits and sexually
      antagonistic traits. More specifically, we need a greater number of functional
      studies of female traits as well as studies of the consequences of both male and
      female traits for female fitness. A mix of selection and manipulative studies on
      these is likely the most promising route.

PMID- 16612888
TI  - Assessing sexual conflict in the Drosophila melanogaster laboratory model system.
AB  - We describe a graphical model of interlocus coevolution used to distinguish
      between the interlocus sexual conflict that leads to sexually antagonistic
      coevolution, and the intrinsic conflict over mating rate that is an integral part
      of traditional models of sexual selection. We next distinguish the 'laboratory
      island' approach from the study of both inbred lines and laboratory populations
      that are newly derived from nature, discuss why we consider it to be one of the
      most fitting forms of laboratory analysis to study interlocus sexual conflict,
      and then describe four experiments using this approach with Drosophila
      melanogaster. The first experiment evaluates the efficacy of the laboratory model
      system to study interlocus sexual conflict by comparing remating rates of females
      when they are, or are not, provided with a spatial refuge from persistent male
      courtship. The second experiment tests for a lag-load in males that is due to
      adaptations that have accumulated in females, which diminish male-induced harm
      while simultaneously interfering with a male's ability to compete in the context
      of sexual selection. The third and fourth experiments test for a lag-load in
      females owing to direct costs from their interactions with males, and for the
      capacity for indirect benefits to compensate for these direct costs.

PMID- 16612889
TI  - The evolutionary outcome of sexual conflict.
AB  - Inter-locus sexual conflict occurs by definition when there is sexually
      antagonistic selection on a trait so that the optimal trait value differs between
      the sexes. As a result, there is selection on each sex to manipulate the trait
      towards its own optimum and resist such manipulation by the other sex. Sexual
      conflict often leads additionally to the evolution of harmful behaviour and to
      self-reinforcing and even perpetual sexually antagonistic coevolution. In an
      attempt to understand the determinants of these different outcomes, I compare two
      groups of traits-those related to parental investment (PI) and to mating-over
      which there is sexual conflict, but which have to date been explored by largely
      separate research traditions. A brief review suggests that sexual conflict over
      PI, particularly over PI per offspring, leads less frequently to the evolution of
      manipulative behaviour, and rarely to the evolution of harmful behaviour or to
      the rapid evolutionary changes which may be symptomatic of sexually antagonistic
      coevolution. The chief determinants of the evolutionary outcome of sexual
      conflict are the benefits of manipulation and resistance, the costs of
      manipulation and resistance, and the feasibility of manipulation. All three of
      these appear to contribute to the differences in the evolutionary outcome of
      conflicts over PI and mating. A detailed dissection of the evolutionary changes
      following from sexual conflict exposes greater complexity than a simple
      adaptation-counter-adaptation cycle and clarifies the role of harm. Not all of
      the evolutionary changes that follow from sexual conflict are sexually
      antagonistic, and harm is not necessary for sexually antagonistic coevolution to
      occur. In particular, whereas selection on the trait over which there is conflict
      is by definition sexually antagonistic, collateral harm is usually in the
      interest of neither sex. This creates the opportunity for palliative adaptations
      which reduce collateral harm. Failure to recognize that such adaptations are in
      the interest of both sexes can hinder our understanding of the evolutionary
      outcome of sexual conflict.

PMID- 16612890
TI  - Lonely hearts or sex in the city? Density-dependent effects in mating systems.
AB  - Two very basic ideas in sexual selection are heavily influenced by numbers of
      potential mates: the evolution of anisogamy, leading to sex role differentiation,
      and the frequency dependence of reproductive success that tends to equalize
      primary sex ratios. However, being explicit about the numbers of potential mates
      is not typical to most evolutionary theory of sexual selection. Here, we argue
      that this may prevent us from finding the appropriate ecological equilibria that
      determine the evolutionary endpoints of selection. We review both theoretical and
      empirical advances on how population density may influence aspects of mating
      systems such as intrasexual competition, female choice or resistance, and
      parental care. Density can have strong effects on selective pressures, whether or
      not there is phenotypic plasticity in individual strategies with respect to
      density. Mating skew may either increase or decrease with density, which may be
      aided or counteracted by changes in female behaviour. Switchpoints between
      alternative mating strategies can be density dependent, and mate encounter rates
      may influence mate choice (including mutual mate choice), multiple mating, female
      resistance to male mating attempts, mate searching, mate guarding, parental care,
      and the probability of divorce. Considering density-dependent selection may be
      essential for understanding how populations can persist at all despite sexual
      conflict, but simple models seem to fail to predict the diversity of observed
      responses in nature. This highlights the importance of considering the
      interaction between mating systems and population dynamics, and we strongly
      encourage further work in this area.

PMID- 16612891
TI  - Sexual conflict and the alternation of haploid and diploid generations.
AB  - Land plants possess a multicellular diploid stage (sporophyte) that begins
      development while attached to a multicellular haploid progenitor (gametophyte).
      Although the closest algal relatives of land plants lack a multicellular
      sporophyte, they do produce a zygote that grows while attached to the maternal
      gametophyte. The diploid offspring shares one haploid set of genes with the
      haploid mother that supplies it with resources and a paternal haploid complement
      that is not shared with the mother. Sexual conflict can arise within the diploid
      offspring because the offspring's maternal genome will be transmitted in its
      entirety to all other sexual and asexual offspring that the mother may produce,
      but the offspring's paternally derived genes may be absent from these other
      offspring. Thus, the selective forces favouring the evolution of genomic
      imprinting may have been present from the origin of modern land plants. In
      bryophytes, where gametophytes are long-lived and capable of multiple bouts of
      asexual and sexual reproduction, we predict strong sexual conflict over
      allocation to sporophytes. Female gametophytes of pteridophytes produce a single
      sporophyte and often lack means of asexual reproduction. Therefore, sexual
      conflict is predicted to be attenuated. Finally, we explore similarities among
      models of mate choice, offspring choice and segregation distortion.

PMID- 16612892
TI  - The dynamics of two- and three-way sexual conflicts over mating.
AB  - We consider mathematical models describing the evolutionary consequences of
      antagonistic interactions between male offence, male defence and female
      reproductive tract and physiology in controlling female mating rate. Overall, the
      models support previous verbal arguments about the possibility of continuous
      coevolutionary chase between the sexes driven by two-way (e.g. between male
      offence and female traits) and three-way (e.g. between male offence, male defence
      and female traits) inter-sexual antagonistic interactions. At the same time, the
      models clarify these arguments by identifying various additional potential
      evolutionary dynamics and important parameters (e.g. genetic variances, female
      optimum mating rates, strength of selection in females and the relative
      contributions of first and second males into offspring) and emphasizing the
      importance of initial conditions. Models also show that sexual conflict can
      result in the evolution of monandry in an initially polyandrous species and in
      the evolution of random mating in a population initially exhibiting non-random
      mating.

PMID- 16612893
TI  - Natural variation in male-induced 'cost-of-mating' and allele-specific
      association with male reproductive genes in Drosophila melanogaster.
AB  - One of the most sharply defined sexual conflicts arises when the act of mating is
      accompanied by an inflated risk of death. Several reports have documented an
      increased death rate of female Drosophila as a result of recurrent mating.
      Transgenic and mutation experiments have further identified components of seminal
      fluid that are at least in part responsible for this toxicity. Variation among
      males in their tendency for matings to be toxic to their partners has also been
      documented, but here for the first time we identify polymorphism within
      particular genes conferring differential post-mating female mortality. Such
      polymorphism is important, as it raises the challenge of whether sexual conflict
      models can provide means for maintenance of polymorphism. Using a set of second
      chromosome extraction lines, we scored differences in post-mating female
      fecundity and longevity subsequent to mating, and identified significant among
      line differences. Seventy polymorphisms in ten male reproductive genes were
      scored and permutation tests were used to identify significant associations
      between genotype and phenotype. One polymorphism upstream of PEBII and an amino
      acid substitution in CG17331 were both associated with male-induced female
      mortality. The same allele of CG17331 that is toxic to females also induces
      greater refractoriness to remating in the females, providing an example of an
      allele-specific sexual conflict. Postcopulatory sexual selection could lead to
      sexual conflict by favouring males that prevent their mates from mating, even
      when there is a viability cost to those females.

PMID- 16612894
TI  - Quantifying the gender load: can population crosses reveal interlocus sexual
      conflict?
AB  - Six sister populations of Drosophila melanogaster kept under identical
      environmental conditions for greater than 600 generations were reciprocally
      crossed to investigate the incidence of population divergence in allopatry.
      Population crosses directly influenced fitness, mating frequency, and sperm
      competition patterns. Changes in both female remating rate and the outcome of
      male sperm competition (P1, P2) in response to foreign males were consistent with
      intersexual coevolution. Moreover, seven of the 30 crosses between foreign mates
      resulted in significant reductions in female fitness, whereas two resulted in
      significant increases, compared to local matings. This tendency for foreign males
      to reduce female fitness may be interpreted as evidence for either sexually
      antagonistic coevolution or the disruption of mutualistic interactions. However,
      instances in which female fitness improved via cohabitation with foreign males
      may better reveal sexual conflict, signalling release from the cost of
      interacting with locally adapted males. By this metric, female reproduction in D.
      melanogaster is strongly constrained by local adaptation by males, a situation
      that would promote antagonistic coevolution between the sexes. We conclude that
      sexual selection can promote population differentiation in allopatry and that
      sexual conflict is likely to have played a role in population differentiation in
      this study system.

PMID- 16612895
TI  - Sensory exploitation and sexual conflict.
AB  - Much of the literature on male-female coevolution concerns the processes by which
      male traits and female preferences for these can coevolve and be maintained by
      selection. There has been less explicit focus on the origin of male traits and
      female preferences. Here, I argue that it is important to distinguish origin from
      subsequent coevolution and that insights into the origin can help us appreciate
      the relative roles of various coevolutionary processes for the evolution of
      diversity in sexual dimorphism. I delineate four distinct scenarios for the
      origin of male traits and female preferences that build on past contributions,
      two of which are based on pre-existing variation in quality indicators among
      males and two on exploitation of pre-existing sensory biases among females.
      Recent empirical research, and theoretical models, suggest that origin by sensory
      exploitation has been widespread. I argue that this points to a key, but perhaps
      transient, role for sexually antagonistic coevolution (SAC) in the subsequent
      evolutionary elaboration of sexual traits, because (i) sensory exploitation is
      often likely to be initially costly for individuals of the exploited sex and (ii)
      the subsequent evolution of resistance to sensory exploitation should often be
      associated with costs due to selective constraints. A review of a few case
      studies is used to illustrate these points. Empirical data directly relevant to
      the costs of being sensory exploited and the costs of evolving resistance is
      largely lacking, and I stress that such data would help determining the general
      importance of sexual conflict and SAC for the evolution of sexual dimorphism.

PMID- 16612896
TI  - Spatial and geographical variations of urban, suburban and rural atmospheric
      concentrations of phenols and nitrophenols.
AB  - GOAL, SCOPE AND BACKGROUND: Atmospheric sampling (gas and particles) of 5 phenols
      (phenol, m-cresol, p-cresol, o-cresol, pentachlorophenol) and 15 nitrophenols (3
      methyl-2-nitrophenol, 3-nitrophenol, 4-methyl-2-nitrophenol, 5-methyl-2
      nitrophenol, 2-methyl-3-nitrophenol, 3-methyl-4-nitrophenol, 2,6-dinitrophenol,
      bromoxynil, 2,5-dinitrophenol, 2,6-dinitropcresol, 2,4-dinitrophenol, ioxynil,
      DNOC, 3,4-dinitrophenol, dinoseb) on XAD-2 resin (20 gr) and glass fibre filters,
      respectively, were performed in 2002 by using 'Digitel DA80' high volume
      sampiers. These measurements were undertaken in order to show spatial and
      geographical variations of concentrations and the role of traffic in the
      emissions of these compounds to the atmosphere. METHODS: Sampling were performed
      in Strasbourg (eastern France), in its vicinity (Schiltigheim) and in Erstein.
      Sites were chosen to be representative of urban (Strasbourg), suburban
      (Schiltigheim) and rural (Erstein) conditions. Field campaigns were undertaken
      simultaneously in urban and suburban sites during all the seasons during 4 hours
      at a flow rate of 60 m3 h(-1), which gives a total of 240 m3 of air per sample.
      Period of sampling varied between 06h00 to 10h00, 11h00 to 15h00 and 18h00 to
      22h00 in order to evaluate a variation of concentration during automobile traffic
      between urban, suburban and rural areas. Gas and particle samples were separately
      Soxhlet extracted for 12 h with a mixture of CH2Cl2 / n-hexane (50:50 v/v),
      concentrated to about 1 mL with a rotary evaporated and finally dried under
      nitrogen. Dry extracts were dissolved in 1 mL of CH3CN. Before analysis, extracts
      were sylilated by using MTBSTFA. Analysis was performed by GC/MSD in the SIM
      mode. RESULTS AND DISCUSSION: Partitioning of phenolic compounds between gas and
      particle phases seems to be mainly correlated with vapour pressure. Among
      phenolic compounds analysed, phenol, p-cresol, pentachlorophenol and 2.4
      dinitrophenol were detected in all samples and emissions from traffic seems to be
      the major source for the presence of these compounds to the atmosphere. No
      increase of concentrations in autumn tend to confirm this hypothesis since, with
      the use of domestic heating in colder months, increases of PAHs concentrations
      were observed and these compounds are known to be emitted by all combustion
      processes, Pentachlorophenol is a special case since this molecule is only used
      as wood preservative. Its presence in all atmospheric samples, whatever the
      locations and the period of time is the consequence of its persistence.
      CONCLUSIONS AND PERSPECTIVES: These measurements demonstrate that phenols and
      nitrophenols are emitted to the atmosphere and further measurements, in order to
      confirm their sources, their behaviour and their potential impact to the air
      quality and to human health should be undertaken especially since the literature
      collected is relatively old. Concentrations of pentachlorophenol measured are
      very low and, due to its toxicity, further investigations should be undertaken.

PMID- 16612897
TI  - Accumulation and chemical fractionation of heavy metals in andisols after a
      different, 6-year fertilization management.
AB  - GOAL, SCOPE AND BACKGROUND: Andisols are widespread in Japan and have some
      special properties such as high anion exchange capacity, low bulk density, and
      high organic matter content, which might influence the accumulation or chemical
      fractionation of heavy metals. However, few such data exist in Japanese andisols.
      The primary objective of this study was to investigate the distribution and
      chemical fractions of Cu, Zn, Ni, and Cr in the soil profiles and subsequently to
      assess their potential environmental hazard. MATERIALS AND METHODS: Soil samples
      were taken from a field experiment conducted on Japanese andisols, which had
      received either swine compost or chemical fertilizers for 6 years. Concentrations
      of Cu, Zn, Ni, and Cr were determined for all of the obtained extract solutions
      by ICP-AES. RESULTS AND DISCUSSION: Considerably higher total concentrations of
      Cu and Zn were observed in the top 20 cm layer of the compost-amended soil,
      relative to the unfertilized soil, while chemical fertilizers had little effect.
      Application of the swine compost increased the concentrations of Cu and Zn, but
      not Ni and Cr, in all fractions in the top 20 cm layer. The greatest increase in
      the organically bound fraction (OM) Cu and dilute acid-exchangeable fraction
      (DAEXCH) Zn was observed. This suggests that Cu and Zn are potentially
      bioavailable and mobile in the andisol profiles after 6-year consecutive
      applications of the swine compost. On the other hand, distribution of Cu, Zn, Ni
      and Cr among various soil fractions was generally unaffected by chemical
      fertilizers. CONCLUSIONS: We observed that 6-year consecutive applications of the
      swine compost led to an increase in total metals of Cu and Zn, as well as their
      all-chemical fractions, in the top 20 cm soil layers. Potential hazard of heavy
      metals, especially of Cu and Zn, as a result of the use of swine compost on
      andisols, must be taken into account. RECOMMENDATIONS AND OUTLOOK: The long-term
      effect of the accumulation of heavy metals, particularly Cu and Zn, in various
      plant tissues and soils, as well as their potential risk to surface water via
      runoff and groundwater via leaching, needs to be carefully considered. Further
      investigations in the long-term experiments are therefore necessary.

PMID- 16612898
TI  - Toxicity of heavy metals on Scenedesmus quadricauda (Turp.) de Brebisson in batch
      cultures.
AB  - BACKGROUND: Aquatic environments are often exposed to various pollutants like
      heavy metals that are released from industrial, agricultural and domestic wastes.
      Emissions of heavy metals can then enter all ecosystems and bring about severe
      problems in plants, especially algae depending on the concentrations of a given
      element. The objective of the investigation presented is to detect toxic effects
      due to some heavy metals in the biomass of green alga Scenedesmus quadricauda.
      METHODS: All experiments were conducted with axenic cultures of the green alga
      Scenedesmus quadricauda (Turp.) de Brebisson (Chlorococcales, Chlorophyta). The
      cultures were grown in Chu-no.10 medium, and optimum physical and chemical growth
      conditions were provided to get higher growth rates and lower doubling times of
      cells. Growth of the micro algal cultures was measured on a daily schedule by
      counting cultures and determination of chlorophyll-a. The sterile-filtered heavy
      metal concentration solutions (Cd, Pb and Cu) were prepared and added as stock
      solutions of their salts (CdCl2*2.5 H2O, Pb(NO3)2*H2O and CuSO4*5 H2O). RESULTS
      AND DISCUSSION: The growth decreased gradually with the alga exposed to Cd at
      0.05, 0.1, and 0.5 mg/L in comparison with the control whereas 1 mg/L Cd2+ had a
      clearly destructive effect. The growth was decreased with Pb at 15, 20 and 25
      mg/L gradually, while at 30 mg/L the effect was more pronounced. When Cu was
      used, the growth was increased gradually at 0.5, 1 and 1.5 mg/L and vice versa at
      2 mg/L. CONCLUSION: There were differences in toxic effects of the metals with
      different metal as well as their concentrations and the time of exposure.

PMID- 16612899
TI  - Transformation and ecotoxicity of carbamic pesticides in water.
AB  - BACKGROUND: N-methylcarbamate insecticides are widely used chemicals for crop
      protection. This study examines the hydrolytic and photolytic cleavage of
      benfuracarb, carbosulfan and carbofuran under natural conditions. Their toxicity
      and that of the corresponding main degradation products toward aquatic organisms
      were evaluated. METHODS: Suspensions of benfuracarb, carbosulfan and carbofuran
      in water were exposed to sunlight, with one set of dark controls, for 6 days, and
      analyzed by 1H-NMR and HPLC. Acute toxicity tests were performed on Brachionus
      calyciflorus, Daphnia magna, and Thamnocefalus platyurus. Chronic tests were
      performed on Pseudokirchneriella subcapitata, and Ceriodaphnia dubia. RESULTS AND
      DISCUSSION: Under sunlight irradiation, benfuracarb and carbosulfan gave off
      carbofuran and carbofuran-phenol, while only carbofuran was detected in the dark
      experiments. The latter was degraded to phenol by exposure to sunlight. Effects
      of pH, humic acid and KNO3 were evaluated by kinetics on dilute solutions in the
      dark and by UV irradiation, which evidenced the lability of the pesticide at pH
      9. All three pesticides and phenol exhibited acute and higher chronic toxicity
      towards the aquatic organisms tested. CONCLUSION: Investigation on the hydrolysis
      and photolysis of benfuracarb and carbosulfan under natural conditions provides
      evidence concerning the selective decay to carbofuran and/or phenol. Carbofuran
      is found to be more persistent and toxic. RECOMMENDATIONS AND OUTLOOK: The decay
      of benfuracarb and carbosulfan to carbofuran and the relative stability of this
      latter pesticide account for many papers that report the detection of carbofuran
      in water, fruits and vegetables.

PMID- 16612900
TI  - Evaluation of measured and predicted environmental concentrations of selected
      human pharmaceuticals and personal care products.
AB  - GOAL, SCOPE AND BACKGROUND: In the past few years, there was an increasing
      awareness of the occurrence of pharmaceuticals and personal care products (PPCPs)
      in surface water and drinking water resources, and measurements in surface water,
      sediment or waste water were done for a number of PPCPs. In the regulatory
      context, an environmental risk assessment (ERA) has become essential for new
      PPCPs. Reliably predicted or measured environmental concentrations (PECs or MECs)
      of chemicals are essential for the exposure assessment, which is one of the two
      main pillars of environmental risk assessment (ERA). This paper reports on
      measured data of selected PPCPs in surface waters and compares the measured
      values with predicted environmental concentrations from exposure models. Such
      models have been proposed by the European Agency for the Evaluation of Medicinal
      Products (EMEA) and the Technical Guidance Document on Risk Assessment for New
      Notified and Existing Chemical Substances (TGD). METHODS: Four pharmaceuticals
      and one personal care product were in the scope of the investigation reported
      here: 17alpha-ethinylestradiol, carbamazepine, sulfamethoxazole and iopromide as
      well as tonalide. Measured environmental concentrations in surface waters for
      these PPCPs were reviewed in the scientific literature. The appropriateness of
      these data was evaluated according to criteria for monitoring data recommended by
      the TGD. A total of 38 references were evaluated with emphasis on the adequacy of
      chemical analysis and the representativeness of sampling. Measurements of
      concentrations in surface water (MECsw), which were found to be adequate for use
      in exposure assessment according to the monitoring quality criteria, were
      averaged and compared with respective PECs in surface water (PECsw) derived from
      exposure modelling (cf. EMEA and TGD). RESULTS AND DISCUSSION: Measured
      environmental concentrations adequate for use in exposure assessment were found
      in 20 out of 38 references. Several of the measurements from Germany could be
      used for a comparison with calculated PECs. Average MECs(sw) in Germany were <
      0.58 ng/L for 17alpha-ethinylestradiol, 454 ng/L for carbamazepine, 126 ng/L for
      sulfamethoxazole, 1105 ng/L for iopromide and 311 ng/L for tonalide. In
      comparison to the measured concentrations, PECs calculated with the model
      proposed by the EMEA in 2001 were in the same range, but slightly higher than the
      MECs. The EMEA model from 2001 is based on a production/use volume of the PPCPs.
      The more recent EMEA model (2003/2005) overestimated the PECs by more than one
      order of magnitude for carbamazepine and sulfamethoxazole, but underestimated the
      concentration of 17alpha-ethinylestradiol by a factor of almost 5 compared to the
      MECs. This model is based on maximum daily doses and the assumption that 1% of
      the population is consuming the pharmaceutical (default value). Calculations with
      the European Union System for the Evaluation of Substances (EUSES), which is part
      of the TGD describing the risk assessment of chemicals and biocides, resulted for
      the investigated pharmaceuticals in almost the same PECs as derived by the older
      EMEA model (2001). For the PCP tonalide, to which the recent EMEA model (2003/
      2005) cannot be applied, the PEC was overestimated by a factor of 3 with the
      older EMEA model (2001), but underestimated with EUSES by a factor of 5 compared
      to the averaged MECsw in Germany. Conclusions. It was shown that PEC calculations
      with exposure models provided by EMEA and the TGD, resulted in PECs very close to
      the corresponding MECs in most cases. However, environmental concentrations can
      be underestimated by models in cases, where, e.g. due to high lipophilicity,
      sorption to sewage sludge is assumed which does not occur to that extent under
      real conditions. Thus, it appears that the exposure models do not come up to the
      complexity of the real environment. However, the main factor with the highest
      impact on predicted environmental concentrations and a high degree of uncertainty
      is the production volume. Recommendations and Outlook. References and their data
      evaluated as not adequate for use in exposure assessment were mainly rejected due
      to missing or insufficient specifications related to the sampling procedure
      and/or representativeness of the samples. Several of the evaluated studies aimed
      at the introduction and establishment of a new analytical methodology. A detailed
      description of sampling frequency and pattern, for example, was therefore
      neglected. Often, a more accurate description of analytical procedure, sampling
      pattern and statistical analysis of data would be sufficient to provide an
      adequate basis for exposure assessment and hence establish confidence in
      environmental risk assessment procedures. For new substances, an exposure
      assessment is solely based on estimations using environmental fate models. To
      avoid unacceptable risks for the environment, PECs should not underestimate
      actual environmental concentrations. Since it was shown that under specific
      conditions the models applied in this study underestimated measured environmental
      concentrations, further development of the calculation models appears to be
      necessary.

PMID- 16612901
TI  - Formaldehyde exposure in a gross anatomy laboratory--personal exposure level is
      higher than indoor concentration.
AB  - GOAL, SCOPE AND BACKGROUND: Cadavers for gross anatomy laboratories are usually
      prepared by using embalming fluid which contains formaldehyde (FA) as a principal
      component. During the process of dissection, FA vapors are emitted from the
      cadavers, resulting in the exposure of medical students and their instructors to
      elevated levels of FA in the laboratory. The American Conference of Governmental
      Industrial Hygienists (ACGIH) has set a ceiling limit for FA at 0.3 ppm. In
      Japan, the Ministry of Health, Labour and Welfare has set an air quality
      guideline defining two limit values for environmental exposure to FA: 0.08 ppm as
      an average for general workplaces and 0.25 ppm for specific workplaces such as an
      FA factory. Although there are many reports on indoor FA concentrations in gross
      anatomy laboratories, only a few reports have described personal FA exposure
      levels. The purpose of the present study was to clarify personal exposure levels
      as well as indoor FA concentrations in our laboratory in order to investigate the
      relationship between them. METHODS: The gross anatomy laboratory was evaluated in
      the 4th, 10th and 18th sessions of 20 laboratory sessions in total over a period
      of 10 weeks. Air samples were collected using a diffusive sampling device for
      organic carbonyl compounds. Area samples were taken in the center and four
      corners of the laboratory during the entire time of each session (4-6 hours).
      Personal samples were collected from instructors and students using a sampling
      device pinned on each person's lapel, and they were 1.1 to 6 hours in duration.
      Analysis was carried out using high performance liquid chromatography. RESULTS
      AND DISCUSSION: Room averages of FA concentrations were 0.45, 0.38 and 0.68 ppm
      for the 4th, 10th and 18th sessions, respectively, ranging from 0.23 to 1.03 ppm.
      These levels were comparable to or relatively lower than the levels reported
      previously, but were still higher than the guideline limit for specific
      workplaces in Japan and the ACGIH ceiling limit. The indoor FA concentrations
      varied depending on the contents of laboratory sessions and seemed to increase
      when body cavity or deep structures were being dissected. In all sessions but the
      4th, FA levels at the center of the room were higher than those in the corners.
      This might be related to the arrangement of air supply diffusers and return
      grills. However, it cannot be ruled out that FA levels in the corners were
      lowered by leakage of FA through the doors and windows. Average personal exposure
      levels were 0.80, 0.45 and 0.51 ppm for instructors and 1.02, 1.08 and 0.89 ppm
      for students for the 4th, 10th and 18th session, respectively. The exposure
      levels of students were significantly higher than the mean indoor FA
      concentrations in the 4th and 10th sessions, and the same tendency was also
      observed in the 18th session. The personal exposure level of instructors was also
      significantly higher than the indoor FA level in the 4th session, while they were
      almost the same in the 10th and 18th sessions. Differences in behavior during the
      sessions might reflect the differential personal exposure levels between students
      and instructors. CONCLUSION: The present study revealed that, if a person is
      close to the cadavers during the gross anatomy laboratory, his/her personal
      exposure level is possibly 2 to 3-fold higher than the mean indoor FA
      concentration. This should be considered in the risk assessment of FA in gross
      anatomy laboratories. RECOMMENDATION AND OUTLOOK: If the risk of FA in gross
      anatomy laboratories is assessed based on the indoor FA levels, the possibility
      that personal exposure levels are 2 to 3-fold higher than the mean indoor FA
      level should be taken into account. Otherwise, the risk should be assessed based
      on the personal exposure levels. However, it is hard to measure everyone's
      exposure level. Therefore, further studies are necessary to develop a method of
      personal exposure assessment from the indoor FA concentration.

PMID- 16612902
TI  - Safety evaluation for a biodiesel process using prion-contaminated animal fat as
      a source.
AB  - BACKGROUND: Due to the bovine spongiform encephalopathy (BSE), specified risk
      material (SRM) as well as animal meat and bone meal (MBM) are banned from the
      food and feed chain because of a possible infection with pathogenic prions
      (PrP(Sc)). Nowadays, prions are widely accepted to be responsible for
      TSE(transmissible spongiform encephalopathies)-caused illnesses like BSE and
      scrapie, and especially for the occurrence of the new variant of CJD in humans.
      Presently, SRM and MBM are burnt under high temperatures to avoid any hazards for
      humans, animals or the environment. The aim of this study was to evaluate a
      method using animal fat separated from Category I material which includes SRM and
      the carcasses of TSE-infected animals, or animals suspected of being infected
      with TSE, as a source for producing biodiesel by transesterification, analogous
      to the biodiesel process using vegetable oil. METHODS: For this purpose, animal
      fat was spiked with scrapie-infected hamster brain equivalents--as representative
      for a TSE-infected animal--and the biodiesel manufacturing process was downscaled
      and performed under lab-scale conditions. RESULTS AND DISCUSSION: The results
      analysed by Western blotting showed clearly that almost each single step of the
      process leads to a significant reduction of the concentration of the pathogenic
      prion protein (PrP(Sc)) in the main and side-products. CONCLUSION: The data
      revealed that the biodiesel production, even from material with a high
      concentration of pathogenic prions, can be considered as safe. RECOMMENDATIONS
      AND OUTLOOK: The obtained results indicated that biodiesel produced from prion
      contaminated fat was safe under the tested process conditions. However, it has to
      be pointed out that the results cannot be generalized because a different process
      control using other conditions may lead to different results and then has to be
      analysed independently. It is clear that the production of biodiesel from high
      risk material represents a more economic usage than the combustion of such
      material.

PMID- 16612903
TI  - Efforts of the European Commission to improve communication between environmental
      scientists and policy-makers.

PMID- 16612904
TI  - The dismantling of end-of-life vehicles in Estonia before putting into effect the
      Directive 2000/53/EC.
AB  - BACKGROUND, AIMS AND SCOPE: When joining the European Union on 1st May 2004,
      Estonia had to conform its legislation to the European Union legislation. In
      relation with that, also the treatment requirements on end-of-life vehicles
      proceeding from Directive 2000/53/EC of the European Parliament and of the
      Council of 18 September 2000 were established in Estonia for the first time.
      Since this area was not regulated with law beforehand, there was not any
      information available about it. The aim of the current survey was to ascertain
      the condition of scrap yards in mid 2004. In addition to that, also to identify
      the number of scrap yards operating in Estonia, to classify these by the number
      of dismantled vehicles and the potential environmental hazard, and to map the
      locations of car dismantling companies and evaluate their compliance with the
      valid requirements. METHODS: The companies that have been registered in the
      Commercial Registry under the activity code 503090-end-of-life vehicle
      dismantling were visited and visually reviewed. During the visits, the compliance
      of scrap yards with the existing requirements was evaluated and it was also
      attempted to identify how environmentally sound the dismantling technology of
      every scrap yard owner is. RESULTS AND DISCUSSION: Altogether, 63 scrap yards
      operated in Estonia by mid 2004. Twelve of them dismantled more than 100
      vehicles, 13 of them 51-99 vehicles and 38 up to 50 vehicles a year. The total
      annual market capacity on dismantling of vehicles in Estonia is considered to be
      approx. 10,000 units. There are very few companies dealing only with car
      dismantling as the main business. Most scrap-yard owners also offer side
      services, e.g. haulage, car repair and maintenance. The dismantlers are
      interested in the selling of second-hand spare parts and scrap metal. Only one
      company out of 63 complied with all the requirements enacted by the relevant
      decision of the Estonian Minister of Environment. The rest of the scrap yards did
      not meet the requirements on the site on storage and treatment nor did they have
      the hazardous waste handling licence or the waste permit. Of the requirements
      established for the site for storage of end-of-life vehicles, 97% of the scrap
      yards were surrounded with a fence, 67% had a 24-hour guard, 45% had covered the
      areas with waterproof cover, but only 3% had an oil trap. Sites for treatment
      were in a somewhat better condition, these were mostly situated inside the
      buildings, where floors were covered with waterproof covers. Most of the
      dismantlers collected the waste oil and waste fluids into separate vessels, but
      there were a number of dismantlers who did not know of existence of
      polychlorinated biphenyls (PCB) in car air conditioning systems and the
      availability of mercury in sensors belonging in passenger safety systems.
      Proceeding from the general condition of the scrap yard, the rest of 62 scarp
      yards were distributed between two empirical parameters--'rather environmentally
      hazardous' or 'rather not environmentally hazardous'. As a matter of fact, 17% of
      scrap yards turned out 'rather environmentally hazardous'. CONCLUSION: Out of the
      scrap yards operating in Estonia, only one is compliant with the requirements set
      up by Directive 2000/53/EC. Another 62 appeared during the review to be sites of
      potential environmental pollution. In order to comply with environmental
      requirements and get the hazardous waste treatment license, the scrap yard owners
      have to invest into state-of-the-art dismantling and environment protection
      equipment. The main obstacle to reach the environmentally sound scrap-yard is the
      high investment cost and the black market for spare parts. RECOMMENDATION AND
      OUTLOOK: As the correction of the market in end-of-life vehicle treatment started
      after the adoption of Directive 2000/53/EC, the environmental authorities have to
      look after the ongoing correction. It is because there is still a demand for
      cheap spare parts and it makes it attractive to dismantle the vehicles out of
      scrap-yards by licensees.

PMID- 16612905
TI  - GLOBOX--a spatially differentiated multimedia fate and exposure model.

PMID- 16612906
TI  - Antimicrobial therapy for intra-abdominal infections: guidelines from the
      Infectious Disease Advisory Board (IDAB).
AB  - Intra-abdominal infection is a common cause of severe sepsis in a hospital
      setting and remains associated with a significant morbidity, mortality and
      resource use. Early adequate surgery or drainage remain the cornerstones of intra
      abdominal infection management and impact on patients outcome. Concomitant early
      and adequate empiric antimicrobial therapy further influences patients morbidity
      and mortality. Multiple empirical regimens have been proposed in this setting,
      but rarely supported by well designed, randomized-controlled studies. The current
      manuscript summarizes the recommendations of the Infection Disease Advisory Board
      on the management of intra-abdominal infections. Empiric antimicrobial therapy
      for the most common causes of abdominal infections is proposed. In addition,
      particular attention has been paid on antibiotic treatment duration.

PMID- 16612907
TI  - How to maintain the quality of laparoscopic surgery in the era of lack of hands?
AB  - Lack of personnel in the operating rooms is not a future problem, it is today's
      reality in many hospitals throughout the OECD countries. As studies anticipate
      that this situation will not change overnight (1), the issue of the quality of
      surgery within this new environment needs to be addressed on short notice. The
      problem is even more critical for laparoscopic surgeons, who have enjoyed
      proportionally more assistance since the emergence of minimally invasive surgery.
      After analyzing the tasks performed by OR assistants and nurses, we have looked
      at available techniques and tools (2) that could help laparoscopic surgeons,
      using the following criteria to assess their benefits : capability to address the
      shortage of assistance, impact on quality of surgery, economic affordability
      within the existing Belgian healthcare system.

PMID- 16612908
TI  - Current trends in superficial venous surgery.

PMID- 16612909
TI  - Endovenous laser treatment for primary varicose veins.
AB  - Venous insufficiency of the lower extremities is a highly prevalent condition.
      Successful treatment of superficial venous insufficiency will most often
      necessitate treatment of the saphenofemoral junction incompetence with correction
      of saphenous vein reflux. In the majority of patients it concerns a reflux of the
      greater saphenous vein. The standard procedure consists of ligation and stripping
      of the greater saphenous vein combined with with additional phlebectomies or
      ligation of insufficient perforant veins if necessary. Although the standard
      procedure is widely known and accepted, the postoperative morbidity and
      postoperative limitations of activity are high. In this context minimally
      invasive percutaneous endovenous techniques were developed to improve the
      patients comfort and faster resumption of work. Among these, endovenous laser
      ablation of the greater saphenous vein is a relatively new procedure.
      Percutaneous introduction of a laser fiber into the incompetent vein and ablation
      with pulsed laser energy is far less invasive than stripping.

PMID- 16612910
TI  - Total laparoscopic aortic aneurysm surgery.
AB  - This paper describes our technique and results with total laparoscopic aortic
      aneurysm repair. MATERIAL AND METHODS: A transperitoneal left retrorenal access
      was used in all cases. Special laparoscopic clamps often in combination with
      balloon catheters were used to occlude the aorta and the renal arteries. Exactly
      the same techniques like in open surgery were used. Either a tube graft or a
      bifurcated graft,anastomosed with the iliac arteries or the femoral arteries, was
      implanted to exclude the aneurysm. Laparoscopic surgery is becoming a third way
      to perform aortic aneurysm repair. In contrast to EVAR it can offer to aneurysm
      patients the same definitive outcome which we obtain in open surgery.

PMID- 16612911
TI  - A defunctioning stoma in the treatment of lower third rectal carcinoma.
AB  - INTRODUCTION: Total mesorectal excision (TME) is the accepted standard for rectal
      cancer treatment. However, there is an increased risk of symptomatic anastomotic
      leakage associated with TME as TME potentially endangers the blood supply of the
      remaining rectum. On top of this, many patients will receive neo-adjuvant radio
      chemotherapy. A defunctioning stoma helps in avoiding severe complications of
      anastomotic failure. MATERIAL AND METHODS: We prospectively collected data of all
      patients with a rectal carcinoma within reach of the palpating finger, operated
      on in our department between December 2000 and January 2005. There were 70
      patients (42 men and 28 women, median age 70 (range 32-95)). RESULTS: In 40
      patients (40/70 = 57%) a sphincter-saving procedure was performed. Eleven
      patients were diagnosed with anastomotic leakage or failure. Seven patients had
      neo-adjuvant radio-chemotherapy, 4 had no neo-adjuvant therapy. In 4 patients
      signs of anastomotic leakage were seen on the barium-enema that is routinely
      performed before closing the defunctioning stoma. Seven patients (7/40 = 17,5%)
      had clinical signs of anastomotic leakage. Three of them could be treated
      conservatively with antibiotics and parenteral nutrition. Two of these patients
      did not have a defunctioning stoma. Four patients needed re-intervention and were
      treated in intensive care for several days. Three of these patients did not have
      a defunctioning stoma. CONCLUSION: Neo-adjuvant radio-chemotherapy and TME
      resection are two factors in the treatment of rectal cancer that might interfere
      with anastomotic healing in the case of a sphincter-saving procedure. The
      construction of a defunctioning stoma helps in limiting the complications of
      anastomotic leakage or failure.

PMID- 16612912
TI  - Early Belgian experience with the Kugel patch inguinal hernia repair.
AB  - The Kugel hernia repair is an open but minimally invasive, tension free repair,
      offering the advantages of a preperitoneal repair without the need for general
      anaesthesia. We report our initial experience with this technique in 25 inguinal
      hernia repairs. Operating time averaged 40 +/- 16 min, and one complication, a
      bladder tear, occurred intra-operatively. Patients were discharged after a median
      of 2 days and were then seen after 3 weeks and after at least one year. Three
      weeks postoperatively, there were two superficial skin inflammations and one
      haematoma. One year post-operatively no recurrences occurred but two patients
      complained of persistent inguinodynia. The Kugel hernia repair is a relatively
      new technique with a short operating time and minimal postoperative pain, but a
      learning curve, comparable to that of TEP has to be overcome in order to
      reproduce the results of its inventor.

PMID- 16612913
TI  - Spiral computerized tomography : a diagnostic aid in patients with atypical acute
      appendicitis.
AB  - This retrospective study aimed to estimate the value of spiral Computerized
      Tomography (sCT) in patients with suspected appendicitis who remained undiagnosed
      after 48 hours of expectant management. We assessed a cohort of 150 patients by
      focused unenhanced sCT. According to the clinical scenario we occasionally
      employed contrast media and extended the scanned area. The major radiological
      signs were appendiceal enlargement and inflammatory changes of periappendiceal
      tissue and mesenteric fat. Regarding acute appendicitis the examination was 95.8%
      sensitive, 97.4% specific, had a positive predictive value of 97.18%, a negative
      predictive value of 96.2% and an accuracy of 96.7%. It also provided alternative
      diagnoses in 55 patients leading correctly 31 of them to the theatre for a
      variety of abdominal surgical diseases. For abdominal surgical pathology in
      general, sCT was 97.1% sensitive, 95.7% specific, had a positive predictive value
      of 98% and a negative predictive value of 93.8%. The importance of good
      communication between the clinicians and radiologists was pointed out by the
      correct alternative diagnoses set by imaging in the 55 patients after modifying
      the sCT protocol and was highlighted by the unnecessary appendectomy of three
      patients with negative imaging. Our results verify the accuracy and value of
      unenhanced sCT in patients with a clinical picture which remains inconclusive
      after an initial period of expectant management.

PMID- 16612914
TI  - Surgical results of leg amputation according to Ghormley's technique in the
      treatment of chronic lower limb ischaemia.
AB  - The authors present their experience in the treatment of chronic lower limb
      ischaemia resulting from atherosclerosis by below knee amputation according to
      Ghormley's technique, with the immediate application of a semi-rigid plaster cast
      and early rehabilitation. From a group of 664 patients requiring major
      amputations, 61 patients (52 men) aged 64 +/- 11 fulfilled the criteria for
      unilateral below-knee amputation for critical limb ischaemia for atherosclerosis
      consequences. Peri-operative (30-days) mortality was of 3.28%. Stump healing was
      very good or good (no need for further surgery) in over 2/3 of patients, but in
      20% the need for above-knee amputation developed. Postoperative knee contracture
      (defined as 15 degrees or more limitation to the movement range) was observed in
      11.5% of patients.

PMID- 16612915
TI  - Comparison of topical glyceryl trinitrate ointment and oral nifedipine in the
      treatment of chronic anal fissure.
AB  - This study was designed to compare the effect of topical glyceryl trinitrate
      (GTN) and oral nifedipine treatments on maximal anal resting pressure (MARP) and
      subsequently to assess their effectiveness in healing of chronic anal fissure
      (CAF). Patients were allocated randomly to receive either oral nifedipine retard
      (10 patients) 20 mg twice daily or instructed to apply glyceryl trinitrate (0.2
      percent) ointment (10 patients) into the lower half of the anal canal twice
      daily. They were reviewed and assessed at the first visit and every fortnight for
      measurement of MARP, pain scores, blood pressure, pulse rate, healing of the
      fissure and adverse effects. Treatment were continued until healing had occurred
      or for up to 8 weeks. MARP values before and after application of the GTN
      ointment was 113.2 cm H2O and 72.5 cm H2O respectively (P < 0.001). Nifedipine
      caused a reduction in mean MARP from 105.2 to 74.0 cm H2O (P < 0.001). Linear
      analogue pain scores were significantly reduced after 2 weeks treatment with GTN
      and nifedipine (P < 0.001) and continued throughout the treatment period. At the
      end of the study; 7 of the 10 patients in the GTN group were deemed to be healed
      (5) or improved (2), compared with 6 of the 10 patients in the nifedipine group
      (5 healed, 1 improved). Headaches occurred in 3 patients in the GTN group,
      compared with one patient in the nifedipine group. There was no significant
      difference between GTN and nifedipine in terms of reduction in MARP and pain
      score, healing of the fissure and incidence of early recurrence and side effects
      of treatments. We conclude that GTN ointment and oral nifedipine are equally
      effective in the treatment of chronic anal fissure.

PMID- 16612916
TI  - The effect of mechanical bowel preparation on colonic anastomotic healing: an
      experimental study.
AB  - PURPOSE: Although bowel preparation is traditionally used in elective colorectal
      surgery, its value is debatable. The aim of this study was to evaluate the
      influence of mechanical bowel preparation on healing of colonic anastomoses.
      MATERIAL AND METHODS: Twenty-seven rats were divided into three groups, each of
      nine animals. All rats had left colonic resection and anastomosis. Group 1 and
      group 2 were the control and sham group, respectively. Group 3 had colonic lavage
      before resection and anastomosis. On the fourth postoperative day, animals were
      killed; bursting pressure and tissue hydroxyproline concentrations were measured
      and compared. RESULTS: The median bursting pressure values were 87 (range 4-135)
      mmHg in group 1, 88 (range 78-136) mmHg in group 2 and 76.0 (range 57.0-125) mmHg
      in group 3. The differences between bursting pressure values of the groups were
      not statistically significant (p= 0.07). The median tissue hydroxyproline
      concentrations were 3.25 (range 2.63-5.16) mg/mg in group 1, 4.15 (range 1.54
      5.72) mg/mg in group 2 and 3.52 (range 2.04-5.27) mg/mg in group 3. The
      differences between tissue hydroxyproline concentrations of the groups were not
      statistically significant (p = 0.7). CONCLUSION: Mechanical bowel preparation is
      not necessary for enhancing colonic anastomotic integrity in the rat.

PMID- 16612917
TI  - Effects of beta-D-glucan on steroid-induced impairment of colonic anastomotic
      healing.
AB  - BACKGROUNDS/AIMS: Inflammation during the early phase of anastomotic wound
      healing is an essential cellular response and is suppressed by corticosteroids.
      The anti-inflammatory effect of corticosteroids is largely responsible for its
      impairment of wound healing in bowel anastomosis. Beta-D-glucan, a commonly used
      macrophage activator, has been shown to improve anastomotic wound healing under
      normal conditions. In the present study, we have investigated the effects of beta
      D-glucan on anastomotic wound healing in rats treated with long-term
      corticosteroid. METHODOLOGY: 92 male Sprague-Dawley rats were randomized into
      four groups. 1 : control, 2: control + beta-D-glucan, 3 : steroid, 4 : steroid +
      beta-D-glucan. Methylprednisolone (5mg/kg) was injected IM daily for 14 days in
      groups 3 and 4. After 14 days, following anaesthesia and laparotomy, colonic
      anastomosis was performed 3 cm away from the peritoneal reflection of rectum. In
      groups 2 and 4, 100mg/kg beta-D-glucan was administered orally for 7 days before
      laparotomy. On postoperative day 3, relaparotomies were performed and bursting
      pressures, hydroxyproline levels and histopathological specimens were studied.
      RESULTS: The mean values of bursting pressures groups were 50.8 (95% CI 46.99
      56.50), 58.2 (95% CI 54.49-61.90), 32.0 (95% CI 29.21-34.98), 45.9 (95% CI 43.09
      48.80) respectively. The differences of the mean values of the groups between
      group 1 and 2 and also 3 were significant (p = 0.002, p < 0.001). The mean values
      of hydroxyproline of the groups were 3.8 (95% CI 3.56-4.06), 4.7 (95% CI 4.50
      5.04), 2.9 (95% CI 2.73-3.20), 3.9 (95% CI 3.65-4.22) respectively. The
      differences of the values of the groups between control (group1) and group 2 and
      also group 3 were significant (p = 0.001, p < 0.001). In histopathological
      examination, increased macrophages and fibroblast population were observed in
      specimens from beta-D-glucan-treated animals. CONCLUSION: The results indicate
      that in rat model, oral administration of beta-D-glucan causes a significant
      improvement in the healing of anastomotic wound impaired by long-term
      corticosteroid administration.

PMID- 16612918
TI  - The effects of desferrioxamine and quercetin on liver injury induced by hepatic
      ischaemia-reperfusion in rats.
AB  - BACKGROUND: This study was designed to examine the effects of desferrioxamine and
      quercetin on hepatic ischaemia-reperfusion injury in rat. METHODOLOGY: Thirty
      Wistar albino rats were randomized into five groups. Group I was the control
      group. Group II received no treatment. Group III and group IV received
      intramuscular injections of desferrioxamine (100 mg/kg per day) and quercetin (50
      mg/kg per day) respectively. Group V was administered desferrioxamine and
      quercetin in combination. After treatment for 3 days, groups II, III, IV, and V
      were exposed to total hepatic ischaemia for 45 minutes. Plasma alanine
      aminotransferase levels, malondialdehyde and reduced glutathione activities were
      measured after reperfusion for 1 hour. Histopathological analysis of liver
      tissues was carried out. RESULTS: Our results indicated that tissue
      malondialdehyde levels and histopathological liver damage scores were
      significantly higher in the ischaemia-reperfusion group than in the control
      group. Administration of desferrioxamine, quercetin, and
      desferrioxamine+quercetin significantly decreased these parameters. Plasma
      alanine aminotransferase levels were also increased after ischaemia-reperfusion.
      Quercetin and desferrioxamine + quercetin significantly decreased the activity of
      this enzyme when compared to ischaemia-reperfusion group. CONCLUSIONS: The
      present data suggest that both desferrioxamine and quercetin may be useful to
      protect against ischaemia-reperfusion induced liver damage.

PMID- 16612919
TI  - Retinoic acid and intestinal wound healing in intra-operatively irradiated rat.
AB  - AIM: This study was undertaken to assess the effect of intra-operative
      radiotherapy on intestinal wound healing and prevention of its side effects by
      retinoic acid. MATERIALS AND METHODS: Thirty Spraque-Dawley rats were divided
      into 3 groups of (n = 10). All the groups had laparatomies and terminal ileum
      exteriorization. Group I was the control group with no irradiation and no
      anastomosis; group II had both irradiation and anastomosis and group III rats had
      peroral retinoic acid conditioning and irradiation + anastomosis. On the seventh
      postoperative day, tensile strength and intestinal elongation measurements were
      to evaluate the effect of retinoic acid on wound healing. RESULTS: Compared to
      the non-retinoic acid conditioned group, the retinoic acid conditioned group had
      statistically significant higher tensile strength and lower intestinal elongation
      values, revealing better wound healing. CONCLUSION: Peroral retinoic acid
      supplement administration has a preventive effect on radiation-induced wound
      healing inhibition in intra-operative abdominopelvic irradiation and anastomoses.

PMID- 16612921
TI  - Follow-up and its importance for long-term pedal bypass functionality.
AB  - Pedal bypasses, for salvage of a critically ischaemic limb, demonstrate excellent
      long-term outcomes. However, regular follow-up of patients and timely detection
      and treatment of a contingent haemodynamically significant bypass stenosis, which
      could cause its thrombosis, are prerequisites. The authors report a case of
      femoropedal bypass graft in which regular duplex follow-up detected critical
      stenoses at 18 months and at 36 months. Patch-angioplasty (at 18 months) and
      percutaneous balloon angioplasty (at 36 months) preserved the long-term patency
      of this pedal bypass graft.

PMID- 16612920
TI  - Pituitary apoplexy after aortic abdominal aneurysm surgery: a case report.
AB  - Pituitary apoplexy (PA) occurring after surgery is a rare but life-threatening
      acute clinical situation following extensive haemorrhage or necrosis within a
      pituitary adenoma. Pituitary apoplexy has been reported to occur spontaneously in
      the majority of cases or in association with various inducing factors. One of the
      pathophysiological mechanism that has been postulated is the fall of arterial
      blood pressure inducing ischaemia followed by infarction of the pituitary gland.
      We report a case of pituitary apoplexy following aortic abdominal surgery. To our
      knowledge, this has not been previously reported. A 73-year old man complained of
      headache and diplopia. At clinical examination, he presented a right oculomotor
      nerve palsy. Magnetic resonance imaging (MRI) showed a haemorrhagic sellar mass.
      In our case, intraoperative hypotension could have been the precipitating factor.
      Diagnostic and therapeutic measures are discussed.

PMID- 16612922
TI  - Surgical repair of residual shunt after transcatheter closure of secundum atrial
      septal defect with an amplatzer septal occluder: a case report.
AB  - Secundum atrial septal defect is the most common congenital heart defect in
      adulthood. As an alternative to surgery, the transcatheter occlusion appears to
      be safe. We herein report a case of a residual shunt after transcatheter closure
      of ASD of a 66 year old man. Surgical repair was indicated. Real and potential
      problem with device closure of ASD are discussed.

PMID- 16612923
TI  - Chylomediastinum following tracheal surgery.
AB  - Chylomediastinum is a rare but serious complication following thoracic
      procedures. A 70-year-old woman underwent tracheal resection through median
      sternotomy. Sternal dehiscence and chylous drainage appeared on the second
      postoperative week. Oral intake was stopped and total parenteral nutrition was
      started. Drainage stopped after two weeks. The region was ligated with a purse
      string suture during revision of sternotomy. A minimal lymph leakage was
      determined on control Tc-99 lymphoscintigraphy, which indicated injury of the
      thoracic duct. The patient has been problem-free for 9 months.

PMID- 16612924
TI  - Toe leiomyoma: A case report with radiological correlation.
AB  - Only a limited number of case reports concerning the magnetic resonance imaging
      appearance of lower extremity leiomyoma have been published. To the best of our
      knowledge, there is not any instance of toe leiomyoma reported with MRI findings.
      We present MRI findings of a toe leiomyoma and discuss the literature.

PMID- 16612925
TI  - Diaphragmatic hydatid disease.
AB  - Hydatid disease caused by echinococcus granulosus is still a serious problem in
      both underdeveloped and developing countries. Clinical signs of the disease are
      not specific. Most patients have no symptom or sign when a hydatid cyst is
      discovered. Symptoms depend on its complications, location and size. Parasite can
      settle in every organ and tissue in the human body. We report two cases with
      diaphragmatic hydatid disease with no other cyst present.

PMID- 16612926
TI  - Endovascular stent-graft placement in the descending aorta through an ascending
      aorto-bifemoral bypass.
AB  - PURPOSE: To report a combined conventional and endovascular strategy to treat a
      descending aorta anastomotic aneurysm. CASE REPORT: A 60-year-old man with
      previous obliteration of the infra renal aorta suffered from bilateral lower limb
      acute ischemia. Lower limb vascularization was provided by a previous thoraco
      bifemoral bypass. Computed tomography and angiography revealed an aortic
      anastomotic false aneurysm and an embolic aspect of the first centimeters of the
      graft. Treatment combined revascularisation of the lower limbs by an ascending
      aorta bifemoral bypass through a median sternotomy and endovascular coverage of
      the false aneurysm by stent-graft placement in the descending aorta. Stent-grafts
      were introduced through a graft's limb and across the anastomosis in the
      ascending aorta. Imaging at 3 months revealed no endoleak and perfect patency of
      the bypass. CONCLUSION: This case illustrates how combined endovascular and
      conventional procedures can minimize surgical risks in complex cases.

PMID- 16612927
TI  - Expanding ulnar artery aneurysm presenting with signs of threatened rupture.
AB  - The case of a 25-year-old man admitted with an ulnar artery aneurysm of the wrist
      is presented. The size of the aneurysm (1.5 x 2.7 cm) and progressive pain gave
      the impression of a threatened rupture. Radiologic examinations confirmed the
      existence of a non-thrombosed ulnar artery aneurysm with occlusion of the 4th and
      5th digital arteries. During an urgent surgical exploration a pseudo-aneurysm was
      found and resected and the artery was repaired. Thrombolysis of the digital
      arteries was performed with a good result. The combination of a large-sized
      pseudo-aneurysm, lack of a history of penetrating trauma and presentation of
      threatened rupture are unique and not reported previously in the literature.

PMID- 16612928
TI  - A rare cause of massive rectal bleeding: internal iliac artery aneurysm.
AB  - Internal iliac artery aneurysm is a rare cause of lower gastro-intestinal tract
      (GIT) haemorrhage. A fifty-four year old male patient presented with massive
      rectal bleeding. Sigmoidoscopy was not conclusive and pelvic angiography revealed
      an aneurysm from a branch off the main trunk of the anterior division of the
      right internal iliac artery that was located in juxtaposition to the sigmoid
      colon. The aneurysm was successfully obliterated by transcatheter arterial
      embolotherapy with acrylic glue. A high index of suspicion of internal iliac
      artery aneurysm as a possible cause of lower GIT haemorrhage is of paramount
      importance. Pelvic angiography is essential for the diagnosis, and embolotherapy
      with acrylic glue was an effective treatment method in this patient.

PMID- 16612929
TI  - Management of a large pseudo-aneurysm secondary to balloon angioplasty for aortic
      coarctation.
AB  - Balloon dilation of native aortic coarctation has been employed safely and
      effectively in selected patients and with good results during follow-up. However,
      pseudo-aneurysm formation at the site of dilatation occurs in about 2%-8% of
      patients. Although the majority of these aneurysms remain stable, they
      occasionally may increase in size during follow-up, raising concerns in regard to
      potential rupture, massive bleeding, and death. We report a case of aneurysm
      formation after balloon dilation of native coarctation of the aorta, treated
      successfully with the interposition of a tube graft.

PMID- 16612930
TI  - Internal herniation with fatal outcome: herniation through an unusual apertura
      between epiploic appendices and greater omentum.
AB  - Internal hernia is an unusal cause of intestinal obstruction. Herniation related
      to epiploic appendix is a very rare entity. We herein report a case of internal
      herniation due to an adhesion between epiploic appendixes and the greater
      omentum. A 71-year-old woman complaining of abdominal pain and intermittent
      nausea was operated on with the pre-operative diagnosis of intestinal
      obstruction. Three epiploic appendixes of the left side of the transverse colon
      and the corresponding part of the greater omentum had created a tunnel and a loop
      of small bowel 25 cm in length was strangulated. No resection was required after
      releiving the strangulation. However, the patient died due to massive myocardial
      infarction in the postoperative period. Internal herniation must be included in
      the differential diagnosis of patients with acute abdomen or intestinal
      obstruction. A high index of suspicion with prompt surgical intervention may be
      the key to the reduction of morbidity and mortality.

PMID- 16612931
TI  - Carcinoid tmour of the common bile duct: report of a case and a review of the
      literature.
AB  - Carcinoid tumours of the common bile duct are extremely rare lesions. In this
      article we report a case with an extrahepatic bile duct carcinoid tumour. A 40
      year-old woman suffered from biliary colic and jaundice. Pre-operative computed
      tomography demonstrated a tumour in the biliary tract. At laparotomy there was a
      tumour invading the common bile duct. Common bile duct resection was performed.
      Carcinoid tumour of the common bile duct was diagnosed histopathologically. For
      extrahepatic bile duct carcinoid tumours surgical resection is the only treatment
      modality that offers a chance to provide a cure and prolonged disease-free
      survival. The favourable histopathological and biological features of these
      tumours encouraged the surgeons to use more aggressive approaches for advanced
      disease.

PMID- 16612932
TI  - An uncommon soft tissue tumour of the chest wall: dermatofibrosarcoma
      protuberans.
AB  - Dermatofibrosarcoma protuberans is a slow-growing tumour with propensity for
      local recurrence. We report herein a case of a 36-year-old man, who presented
      with a huge, recurrent tumour arising from the left upper anterior part of his
      chest wall. We performed a wide excision with 4 cm free skin margins.
      Reconstruction was performed with a pedicled latissimus dorsi musculocutaneous
      flap and free split skin grafts. Histologic and immunohistochemical studies
      revealed the lesion to be dermatofibrosarcoma protuberans.

PMID- 16612933
TI  - Persistent mullerian duct syndrome associated with irreducible inguinal hernia,
      bilateral cryptorchidism and testicular neoplasia: a case report.
AB  - Persistent mullerian duct syndrome is a rare form of male pseudohermaphroditism.
      A case is reported of normal male appearance with bilateral cryptorchidism and a
      right irreducible inguinal hernia. On exploration, an uterus with two fallopian
      tubes and a testicle were found in the hernia sac. The uterus, fallopian tubes
      and left testicle were en bloc removed. Right orchidopexy and hernia repair were
      performed. In conclusion, if there is an adult bilateral cryptorchidism, surgeons
      should take into consideration a persistent mullerian duct syndrome.

PMID- 16612934
TI  - Eccrine porocarcinoma: a case report.
AB  - Eccrine porocarcinoma is a rare malignant sweat gland tumour. Clinical
      presentation can vary from an indurated plaque to a polypoid ulcerated and
      bleeding lesion. Diagnosis of eccrine porocarcinoma on clinical observation only
      is quite impossible. Here we present the case of a 64-year-old female patient
      with a small reddish nodule of the knee that, on histological evaluation, proved
      to be an eccrine porocarcinoma.

PMID- 16612935
TI  - Multifocal tuberculosis of the chest wall without pulmonary involvement.
AB  - Skeletal tuberculosis (TB) is usually seen in association with a primary
      pulmonary focus. However, it is being increasingly recognized that the former may
      be encountered without the latter, particularly in children. Sternal lesions have
      been frequently reported in infants, presumably secondary to Bacillus Calmette
      Guerin (BCG) vaccination. Herein we report a case of rib TB and a cold abscess in
      a child who had previously had sternal TB ; that diagnosis had been missed at the
      time. Timely treatment of apparently solitary skeletal lesions may reduce the
      number of multifocal cases of skeletal TB in children.

PMID- 16612936
TI  - Primary pulmonary lymphoma disguised as asthma.
AB  - Primary pulmonary lymphomas (PPL) only constitute 4% of extra-nodal, non-Hodgkin
      lymphomas (NHL), less than 1% of NHL in general, and between 0.5% and 1% of
      malignant pulmonary neoplasms. Fifty-eight to 87% of cases of this extremely
      uncommon disease are low-grade B-cell lymphomas and 11%-19% are high-grade or
      large B-cell lymphomas. The prognosis for.high-grade or large B-cell lymphomas is
      worse than for low-grade lymphomas; respiratory and general symptoms are usually
      present. However asthmatic symptoms are not often found in their clinic. We
      report the case of a 49-year old woman with resistant asthma clinic in the form
      of wheezing, dyspnea and non-productive painless cough; associated with an
      irregular lobulated mass with air bronchograms in the lower lobe of the right
      lung. Histological diagnosis showed a pattern of high-grade B-cell lymphoma and
      all asthmatic symptoms disappeared following gross total resection of this
      lesion.

PMID- 16612937
TI  - David van mauden (+/- 1538 +/- 1597), "sworn medical doctor and surgical
      prelector of antwerp", and his book on anatomy.

PMID- 16612938
TI  - [Patients expect counseling from the family physician. Don't exclude "sex" !].

PMID- 16612939
TI  - [Acute abdominal pain caused by vascular occlusion].

PMID- 16612940
TI  - [Erroneous recommendation results in steep increase of sudden infant deaths.
      Prone position-induced catastrophy].

PMID- 16612942
TI  - [Effective for one year and longer].

PMID- 16612941
TI  - [How do you manage difficult patients? (interview by Friederike Klein)].

PMID- 16612943
TI  - [Patient with joint problem or hypertension wants to jog. Do you allow him to
      run? (interview by Dr. Thomas Meissner)].

PMID- 16612944
TI  - [First aid, adequate therapy and after care for fractures of the extremities.
      Quick return to health].

PMID- 16612945
TI  - [Primary care of fractures of the extremities].
AB  - The initial care of a fractured bone provided by the general physician includes
      reduction followed by immobilization and the treatment of pain. Open fractures
      must be covered by a sterile dressing, prior to the transportation of the patient
      to a hospital. Depending upon the severity of the injury, further treatment is
      provided by an orthopedic surgeon or in an appropriate hospital.

PMID- 16612946
TI  - [Fractures of the extremities--surgical or conservative treatment?].
AB  - When a fracture of an extremity has been established, the question immediately
      arises: should it be treated conservatively or surgically? For each of these
      options the three "R's" of fracture treatment apply "reduction, retention,
      rehabilitation". In humans, the most common fracture is that of the distal
      radius, which is usually amenable to conservative treatment. A fracture of the
      ankle is treated conservatively only when it is stable with no syndesmotic
      injury, and the fragments are in good alignment. Should surgical treatment be
      necessary, stabilization is accomplished with a plate and screws. The advantages
      and disadvantages of each of the options must be weighed up on an individual
      basis.

PMID- 16612947
TI  - [After care of fractures of the extremities].
AB  - Today, early mobilization is recommended, irrespective of whether a patient with
      a fracture of the extremities has been treated conservatively or surgically. In
      this way, morbidity and mortality risks can be considerably reduced, in
      particular in the elderly patient. As a result of the continuing trend towards an
      ever shorter hospital stay, the general physician is faced with the task of
      providing aftercare to such patients at an early stage in the healing process of
      the fracture. This includes wound care, prevention of thromboembolism, the timely
      initiation of physiotherapeutic measures, and the requesting of x-ray follow-up.

PMID- 16612948
TI  - [Dysmorphophobia].
AB  - In the ICD-10 classification, the body dysmorphophobic (dysmorphic) disorder is
      subsumed under the code for somatoform or hypochondriacal disorders (F45.2). To
      the fore is an excessive preoccupation with an imagined, but not objectifiable,
      bodily defect, usually affecting a part of the body that is either exposed or
      considered to be of importance for the patient's attractiveness. In many cases,
      the patient insistently demands surgical correction. During the further course of
      the condition, depression, social phobia, obsessive-compulsive and self
      destructive behavior may develop. The condition usually begins early in the
      patient's life, and the lifetime prevalence is estimated to be 5%. Since an
      involvement of the serotonergic system is assumed, selective serotonin reuptake
      inhibitors are considered to be the medication of first choice. Surgical
      interventions do not lead to remission but simply to a transference of symptoms.
      Referral to a psychiatric specialist with the aim of clarifying the diagnosis is
      indicated.

PMID- 16612949
TI  - [Where do skin pigment spots come from?].

PMID- 16612950
TI  - [Will prescribing all types of insulin no longer be allowed?].

PMID- 16612951
TI  - [One brown eye and one blue eye--bad mood of nature].

PMID- 16612952
TI  - [Singultus: indication of an atypical myocardial infarct?].

PMID- 16612953
TI  - [A hairy situation].

PMID- 16612954
TI  - [Do you recognize the pseudo-physician?].

PMID- 16612955
TI  - [So you become the aphthae master].

PMID- 16612956
TI  - [Even in fever, joint pain and erythema: Borrelia antibodies do not prove Lyme
      disease].

PMID- 16612957
TI  - [Are the short-acting insulin analogs superfluous?].

PMID- 16612958
TI  - [How healthy is healing fasting?].

PMID- 16612959
TI  - [Thromboembolisms endanger the internist patients, too: who needs heparin].

PMID- 16612960
TI  - [Exercise ECG, lung function and gastroenterological tests. Function testing in
      the doctor's office].

PMID- 16612961
TI  - [The exercise ECG in the general physician's office].
AB  - In the majority of cases, the exercise ECG serves to confirm or exclude the
      presence of myocardial ischaemia. It is applied both as a primary diagnostic tool
      in CAD patients with dyspnea or chest pain, and also to monitor the success of
      treatment. It is, however, important to remember that the information provided by
      an exercise ECG will vary depending on the patient's age and individual
      circumstances, and this may make additional investigations necessary.

PMID- 16612962
TI  - [Pulmonary function tests in the family doctor's office].
AB  - The basic diagnostic work-up including history-taking, clinical findings, and
      simple functional tests alone, suffices to enable the family doctor to rapidly
      differentiate between an obstructive and a restrictive pulmonary disease. This in
      particular by determining the "Tiffenau index", the ratio of the forced
      expiratory volume FEV1 to the forced vital capacity FVC (FEV1/ FVC). The question
      as to whether an obstructive condition is due to COPD or bronchial asthma is
      decided on the basis of the bronchospasmolytic test to determine the
      reversibility of the airways obstruction.

PMID- 16612963
TI  - [Gastroenterological function tests in the GP's office].
AB  - Breath tests are quick, noninvasive, simple to perform and reliable. In
      particular in patients with diarrhea, bloating, nausea and uncharacteristic
      abdominal symptoms, the H2 breath test is highly useful. Using this procedure,
      malabsorption of various different carbohydrates, the absorptive performance of
      the upper abdominal tract, the orocecal transit time, or bacterial overgrowth in
      the small bowel, can be determined. Using 24-hour pH-metry, the acidity in the
      stomach and esophagus can be measured, and reflux disease, for example,
      diagnosed. Today, elevated fat in the stool is detected on the basis of the beta
      carotene level in the serum. Further function tests for the detection of
      pancreatic insufficiency, such as the determination of fecal pancreatic elastase,
      are also available.

PMID- 16612964
TI  - [Dermatitis artefacta (factitial dermatitis)--an interdisciplinary diagnostic and
      therapeutic challenge].
AB  - Factitial cutaneous lesions result from self-inflicted injury leading to
      objectifiable clinically relevant damage to the skin. Triggering factors are
      frequently psychiatric disorders or specific stress situations. Clinical
      manifestations range from superficial erosions to deep wounds.The establishment
      of the diagnosis is often a time-consuming and complicated process that precedes
      acceptance of the underlying pathology by both the therapist and patient. If
      lasting therapeutic success is to be achieved, the possibility of such cutaneous
      lesions must be included in differential diagnostic considerations, and early
      interdisciplinary cooperation is necessary.

PMID- 16612965
TI  - [Antihypertensive therapy: risk stratification in diabetes and cardiac diseases].

PMID- 16612966
TI  - [Rather work again as employee?].

PMID- 16612967
TI  - [Airway diseases--leukotriene antagonist kills two flies with one fly-flap].

PMID- 16612968
TI  - [Allergic asthma and allergic rhinitis. Many similarities].

PMID- 16612969
TI  - [Muscle cramp--what is at the bottom of it? Only a little strained or seriously
      sick?].

PMID- 16612970
TI  - [At first backache, then acne].

PMID- 16612971
TI  - Co-culture of Trypanosoma musculi with spleen-derived adherent fibroblasts:
      possible transfer of small molecules via connexons.
AB  - Trypanosoma musculi, a protozoan parasite specific to mouse, was cultured in
      vitro in the presence of spleen-derived adherent cells. T. musculi co-cultured
      with adherent cells survived and proliferated indefinitely as long as cellular
      contact was retained. Scanning and transmission electron microscopy confirmed
      intimate membrane-to-membrane contact between the adherent cells and parasites.
      Cellular contact, therefore, seemed to be essential for trypanosomal survival and
      growth. Immunocytochemical studies demonstrated intense fibroblast growth factor
      (FGF) activity in adherent cells, and FGFR-2 in associated trypanosomes.
      BioPorter Lucifer yellow protein delivery reagent studies demonstrated that
      Lucifer yellow transfected into fibroblast was incorporated into associated
      trypanosomes. The results suggest the existence of viable channels reminiscent of
      gap junctions between associated cells. Such transfer of low molecular weight
      molecules might represent antiapoptotic metabolic factors that support survival
      of adherent trypanosomes in vitro. Immunocytochemical studies also detected
      connexin-32 and connexin-43 in the cytoplasm of fibroblasts and associated
      trypanosomes, however, restriction of connexons to trypanosome/fibroblast
      adherent sites was not observed. Western blots confirmed the presence of connexin
      protein molecules in trypanosomes.

PMID- 16612972
TI  - The myofibroblast: a study of normal, reactive and neoplastic tissues, with an
      emphasis on ultrastructure. part 2 - tumours and tumour-like lesions.
AB  - This paper describes the ultrastructure of the commoner myofibroblastic tumours
      and tumour-like lesions. The objective is to complement mainstream pathology
      texts, which have concentrated on the clinical and light microscopy features of
      these lesions and which have arguably but understandably somewhat neglected
      electron microscopy as an ancillary diagnostic tool and a technique for
      investigating tumour cell biology. Ultrastructural features are described of
      nodular fasciitis, the myofibromatoses (including Dupuytren's disease),
      inflammatory myofibroblastic tumour, post-operative spindle cell nodule, fibroma
      of tendon sheath, fibrous pseudotumour, benign fibrous histiocytoma, atypical
      fibroxanthoma, dermatofibrosarcoma protuberans, myofibrosarcoma (myofibroblastic
      sarcoma), malignant fibrous histiocytoma (pleomorphic myofibrosarcoma),
      epithelioid sarcoma and spindle-cell carcinoma. Fibrosarcoma and leiomyosarcoma
      are illustrated for comparison. The fibronexus is emphasised as an important
      marker for the most confident diagnosis of myofibrosarcoma. Some pathologists
      accept a light microscope definition, which includes alpha-smooth-muscle actin
      positivity, h-caldesmon negativity and, in some cases, desmin positivity. Caution
      in the interpretation of desmin staining in a possible myofibroblastic lesion is
      urged, since, in combination with an ultrastructurally identified lamina, it more
      probably suggests true smooth-muscle differentiation. Myofibroblastoma and
      angiomyofibroblastoma are examples of tumours argued on the basis of
      ultrastructural findings (sometimes in combination with desmin staining) to be
      primitively differentiated smooth-muscle cell rather than myofibroblastic
      proliferations.

PMID- 16612973
TI  - 'Round head' sperm defect. Ultrastructural and meiotic segregation study.
AB  - The sperm 'round head' defect, also known as globozoospermia, is an uncommon
      alteration of sperm morphology generally characterised by 100% round headed sperm
      totally lacking an acrosome. This alteration is a genetic sperm defect as
      demonstrated by analysing the incidence of these alterations in a population of
      infertile men showing a history of consanguinity and cases belonging to the same
      family. Ultrastructural characteristics and meiotic segregation in spermatozoa
      from two patients affected by 'round head' sperm defect were investigated. The
      sperm quality was examined by light and transmission electron microscopy (TEM)
      and fluorescence in situ hybridization (FISH) analysis was performed in order to
      investigate the meiotic behavior of chromosomes namely gonosomes and chromosome
      18. TEM analysis, mathematically elaborated, clearly diagnosed the 'round head'
      genetic sperm defect and highlighted at the same time the presence of other
      phenotypic alterations belonging to pathologies such as immaturity, apoptosis and
      necrosis. It is possible to hypothesize that round headed sperm could be a 'weak
      phenotype' allowing the sperm pathologies to overlap with a sperm defect of
      genetic origin, further compromising fertilizing potential. FISH analysis
      revealed a positive correlation between globozoospermia and higher disomies of
      sex chromosomes and diploidies suggesting a higher risk of creating an aneuploid
      embryo after intracytoplasmic sperm injection.

PMID- 16612974
TI  - Reduplicated basal lamina of the peritubular capillaries in renal biopsy
      specimens.
AB  - Reduplicated basal lamina of the peritubular capillaries (PTC) is usually found
      in kidney allografts in association with chronic transplant nephropathy and
      sometimes in native renal biopsies. In order to assess the incidence of this
      phenomenon in native renal biopsy specimens, we have carried out a retrospective
      review of the diagnostic ultrastructural pathology records of 80 consecutive
      renal biopsies excluding renal allografts and children with clinical signs of
      heavy proteinuria. Reduplicated basal lamina of the PTC was found in 19 out of
      the 80 cases (23.8%) with renal diseases. It was frequently seen in lupus
      nephritis, IgA nephropathy, and membranoproliferative glomerulonephropathy, being
      the subtypes of mesangial proliferative lesions. In a few cases it was also found
      in anti-neutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis
      and benign nephrosclerosis renal biopsies. Reduplicated basal lamina of the PTC
      was strongly associated with glomerular and peritubular inflammation, and tubular
      necrosis. Peritubular interstitial edema, slight to moderately increased collagen
      fibrils, many spiraled collagen fibrils (indicative of degeneration), and
      collagen fibrils drawing from basal lamina were found around the reduplicated
      basal lamina of the PTC but not in normal basal lamina. These results indicate
      that in native renal biopsy specimens, reduplication of the basal lamina of the
      PTC is associated with endothelial cell injury and capillary permeability
      abnormality.

PMID- 16612975
TI  - Sperm morphology of mud dauber Sceliphron fistularium dahlbom (Hymenoptera:
      Apoidea: Sphecidae), as an indication of bees relation.
AB  - The morphology of spermatozoon of Sceliphron fistularium is very similar to that
      described for bees. In particular, the response to E-PTA stains is similar to
      that observed in corbiculated Apidae, especially Meliponini bees. Spermatozoa
      measure 285 microm and are composed of 1) a bilayered acrosome (acrosomal vesicle
      and perforatorium); 2) a homogeneous and compact nucleus; 3) a 9+9+2 axoneme; 4)
      a rod-shaped centriolar adjunct; 5) two asymmetrical mitochondrial derivatives
      with paracrystalline material exclusively in the larger one, and 6) two accessory
      bodies. Only the accessory microtubules of axoneme and the paracrystalline
      material are E-PTA positive. Comparison of S. fistularium sperm to data on
      Hymenoptera corroborates their proximity with bees.

PMID- 16612976
TI  - Fine structure of juvenile feathers of the zebrafinch in relation to the
      evolution and diversification of pennaceous feathers.
AB  - The present ultrastructural study describes the formation of feather ramification
      in developing juvenile feathers of the zebrafinch, a small passeraceous bird. The
      study stresses the importance of the detailed knowledge on the cell structure of
      barb ridges for the understanding of feather development and evolution. Feather
      formation depends on the morphogenesis of long barb ridges, in which cells are
      displaced into lateral barbule plates and a medial barb cells region. These cells
      merge into long chains and form a syncitium organized in a ramified structure
      that preserves the original cell disposition within the barb ridge. Barb vane
      ridge cells surround barb and barbule cells. Barbules separate after the
      degeneration of barb vane ridge cells. In barbule cells the formation of hooklets
      resembles the process of formation of climbing setae of digital pads of some
      lizards. The cytoplasm of barb vane ridge cells is localized among tile-like
      overlapped barbule cells that form barbule chains, and maintains a serrated
      outline. When barb vane ridge cells degenerate among keratinized barbules,
      keratinized hooklets remain. Hooklets allow the ordered grasping of barbules to
      form a close and planar vane of feathers. The rachis of juvenile feathers seems
      to be formed from the fusion of two or more barb ridges localized in the dorsal
      part of the follicle, but the process of fusion is unclear. Juvenile and adult
      feathers contain the same type of feather keratin present in downfeathers: this
      indicates that stem cells for the regeneration of a new feather remain in the
      follicle after shedding of downfeathers. The presence of embryonic organelles
      (periderm granules) in barb vane ridge cells of juvenile feathers further
      indicates that also stem cells for the regeneration of the latter cells remain in
      the follicle. Molting feathers are therefore derived from stem cells. The
      permanence of stem cells in the follicle and the modulation of barb ridges
      dimension and fusion into different patterns allow the production of different
      feather morphotypes such as contour, filoplumes, semiplumes, and bristles.

PMID- 16612977
TI  - Metallothioneins and zinc dysregulation contribute to neurodevelopmental damage
      in a model of perinatal viral infection.
AB  - Neonatal Borna disease (NBD) virus infection in the Lewis rat results in life
      long viral persistence and causes behavioral and neurodevelopmental
      abnormalities. A hallmark of the disorder is progressive loss of cerebellar
      Purkinje and dentate gyrus granule cells. Findings of increased brain
      metallothionein-I and -II (MT-I/-II) mRNA expression in cDNA microarray
      experiments led us to investigate MT isoforms and their relationship to brain
      zinc metabolism, cellular toxicity, and neurodevelopmental abnormalities in this
      model. Real-time PCR confirmed marked induction of MT-I/-II mRNA expression in
      the brains of NBD rats (40.5-fold increase in cerebellum, p<0.0001; 6.8-fold
      increase in hippocampus, p=0.003; and 9.5-fold increase in striatum, p=0.0012),
      whereas a trend toward decreased MT-III mRNA was found in hippocampus (1.25-fold
      decrease, p=0.0841). Double label immunofluorescence revealed prominent MT-I/-II
      expression in astrocytes throughout the brain; MT-III protein was decreased in
      granule cell neurons and increased in astrocytes, with differential subcellular
      distribution from cytoplasmic to nuclear compartments in NBD rat hippocampus.
      Modified Timm staining of hippocampus revealed reduced zinc in mossy fiber
      projections to the hilus and CA3, accumulation of zinc in glial cells and
      degenerating granule cell somata, and robust mossy fiber sprouting into the inner
      molecular layer of the dentate gyrus. Zinc Transporter 3 (ZnT-3) mRNA expression
      was decreased in hippocampus (2.3-fold decrease, p= 0.0065); staining for its
      correlate protein was reduced in hippocampal mossy fibers. Furthermore, 2
      molecules implicated in axonal pathfinding and mossy fiber sprouting, the
      extracellular matrix glycoprotein, tenascin-R (TN-R), and the hyaluronan receptor
      CD44, were increased in NBD hippocampal neuropil. Abnormal zinc metabolism and
      mechanisms of neuroplasticity may contribute to the pathogenesis of disease in
      this model, raising more general implications for neurodevelopmental damage
      following viral infections in early life.

PMID- 16612978
TI  - NF2 mutations in secretory and other rare variants of meningiomas.
AB  - The WHO classification defines different histological variants of meningiomas.
      Mutations of the tumor suppressor gene NF2 on 22q have been described in 30% to
      60 % of sporadic meningiomas. However, the vast majority of the meningiomas that
      have been subject to NF2 analysis belong to the most frequent variants like
      transitional, fibroblastic and meningothelial meningiomas. Within these subtypes,
      transitional and fibroblastic meningiomas harbor significantly more NF2 mutations
      than meningothelial meningiomas, indicating molecular subsets of these tumors. To
      determine whether rare meningioma variants carry NF2 mutations we analyzed 80
      tumors. NF2 mutations were detected in 5 (36%) of 14 psammomatous, 1 (11%) of 9
      angiomatous, 2 (22%) of 9 clear cell, 1 (33%) of 3 chordoid and 1 (100%) of 1
      papillary meningioma. In the single papillary meningioma, 2 different NF2
      mutations were observed. No NF2 mutations were found in 33 secretory, 7
      microcystic, 2 lymphoplasmacyte-rich, one rhabdoid and one metaplastic
      meningioma. In the control group of 25 fibroblastic meningiomas, 11 cases were
      identified to carry an NF2 mutation. These results support the concept of
      different molecular subgroups of meningiomas which overlap with histological
      variants.

PMID- 16612979
TI  - Human herpesvirus 6 and multiple sclerosis: a one-year follow-up study.
AB  - BACKGROUND: This study was undertaken in order to investigate the possible
      relation of HHV-6 and EBV in relapsing-remitting MS (RRMS). MATERIALS AND
      METHODS: A one-year follow up study was performed analysing peripheral blood
      mononuclear cells and serum samples of 57 patients with RRMS and 57 healthy blood
      donors (HBD) by a quantitative real time PCR, to detect HHV-6 and EBV. Clinical
      data (starting age and EDSS increase) were collected. RESULTS: We did not find
      any statistically significant difference for EBV between RRMS patients and HBD.
      Regarding HHV-6: i) There was a higher prevalence of HHV-6 in RRMS patients than
      in controls: 80.7% versus 29.8% respectively. ii) HHV-6 active replication seems
      to be related to exacerbations. iii) Only variant A was detected among RRMS
      patients with HHV-6 active replication. iv) Although some difference was found
      when we compared clinical data in RRMS patients with and without HHV-6 active
      replication, the results did not reach statistical significance. CONCLUSIONS: A
      higher HHV-6A frequency of active infection (reactivation or new infection) would
      lead to a more frequent exposure of HHV-6A antigens to the immune system of RRMS
      patients; this active replication of HHV-6A seems to be specifically related with
      the exacerbations in a subset of RRMS patients.

PMID- 16612980
TI  - The cerebral beta-amyloid angiopathies: hereditary and sporadic.
AB  - We review the clinical, radiologic, and neuropathologic features of the
      hereditary and sporadic forms of cerebral amyloid angiopathy (CAA) associated
      with vascular deposition of the beta-amyloid peptide. Amino acid substitutions at
      4 sites in the beta-amyloid precursor protein, all situated within the beta
      amyloid peptide sequence itself, have been shown to cause heritable forms of CAA.
      The vascular diseases caused by these mutations are associated primarily with
      cerebral hemorrhages, white matter lesions, and cognitive impairment, and only
      variable extents of the plaque and neurofibrillary pathologies characteristic of
      Alzheimer disease. Sporadic CAA typically presents 20 or more years later than
      hereditary CAA, but is otherwise characterized by a comparable constellation of
      recurrent cerebral hemorrhages, white matter lesions, and cognitive impairment.
      The clinical, radiologic and pathologic similarities between hereditary and
      sporadic CAA suggest that important lessons for this common age-related process
      can be learned from the mechanisms by which mutation makes beta-amyloid tropic or
      toxic to vessels.

PMID- 16612981
TI  - Mechanism of cerebral beta-amyloid angiopathy: murine and cellular models.
AB  - Cerebral amyloid angiopathy of the beta-amyloid type (Abeta-CAA) is a risk factor
      for hemorrhagic stroke and independently is believed to contribute to dementia.
      Naturally occurring animal models of Abeta-CAA are scarce and not well suited for
      the laboratory. To this end, a variety of transgenic mouse models have been
      developed that, similar to cerebral Abeta-amyloidosis in humans, develop either
      Abeta-CAA only or both Abeta-CAA and parenchymal amyloid, or primarily
      parenchymal amyloid with only scarce Abeta-CAA. The lessons learned from these
      mouse models are: i) Abeta-CAA alone is sufficient to induce cerebral hemorrhage
      and associate pathologies including neuroinflammation, ii) the origin of vascular
      amyloid is mainly neuronal, iii) Abeta-CAA results largely from impaired Abeta
      clearance, iv) a high ratio Abeta40:42 favors vascular over parenchymal
      amyloidosis, and v) genetic risk factors such as ApoE modulate Abeta-CAA and CAA
      induced hemorrhages. Therapeutic strategies to inhibit Abeta-CAA are poor at the
      present time. Once Abeta-CAA is present current Abeta immunotherapy strategies
      have failed to clear vascular amyloid and even run the risk of serious side
      effects. Despite this progress in deciphering the pathomechanism of Abeta-CAA,
      with these first generation mouse models of Abeta-CAA, refining these models is
      needed and will help to understand the emerging importance of Abeta-CAA for
      dementia and to develop biomarkers and therapeutic strategies.

PMID- 16612982
TI  - Hereditary cystatin C amyloid angiopathy: genetic, clinical, and pathological
      aspects.
AB  - Hereditary cystatin C amyloid angiopathy (HCCAA) is a rare, fatal amyloid disease
      in young people in Iceland caused by a mutation in cystatin C, which is an
      inhibitor of several cysteine proteinases, such as cathepsins S, B, and K. The
      same mutation in cystatin C, L68Q, has been found in all patients examined so far
      pointing to a common founder. Most of the families can be traced to a region in
      the northwest of Iceland, around Breidafjordur bay. Mutated cystatin C forms
      amyloid, predominantly in brain arteries and arterioles, but also to a lesser
      degree in tissues outside the central nervous system such as skin, lymph nodes,
      testis, spleen, submandibular salivary glands, and adrenal cortex. The amyloid
      deposition in the vessel walls causes thickening of the walls leading to
      occlusion or rupture and resulting in brain hemorrhage. Although the amyloid can
      be detected outside the brain, the clinical manifestation is restricted to the
      brain, and usually consists of repeated hemorrhages leading to paralysis.
      Sometimes the initial signs of hemorrhage are dementia and personality changes.

PMID- 16612983
TI  - The role of cystatin C in cerebral amyloid angiopathy and stroke: cell biology
      and animal models.
AB  - A variant of the cysteine protease inhibitor, cystatin C, forms amyloid deposited
      in the cerebral vasculature of patients with hereditary cerebral hemorrhage with
      amyloidosis, Icelandic type (HCHWA-I), leading to cerebral hemorrhages early in
      life. However, cystatin C is also implicated in neuronal degenerative diseases in
      which it does not form the amyloid protein, such as Alzheimer disease (AD).
      Accumulating data suggest involvement of cystatin C in the pathogenic processes
      leading to amyloid deposition in cerebral vasculature and most significantly to
      cerebral hemorrhage in patients with cerebral amyloid angiopathy (CAA). This
      review focuses on cell culture and animal models used to study the role of
      cystatin C in these processes.

PMID- 16612984
TI  - Genetic alterations of the BRI2 gene: familial British and Danish dementias.
AB  - Classic arguments sustaining the importance of amyloid in the pathogenesis of
      dementia are usually centered on amyloid beta (Abeta) and its role in neuronal
      loss characteristic of Alzheimer disease, the most common form of human cerebral
      amyloidosis. Two non-Abeta cerebral amyloidoses, familial British and Danish
      dementias, share many aspects of Alzheimer disease, including the presence of
      neurofibrillary tangles, parenchymal pre-amyloid and amyloid deposits, cerebral
      amyloid angiopathy, and a widespread inflammatory response. Both early-onset
      conditions are linked to specific mutations in the BRI2 gene, causing the
      generation of longer-than-normal protein products and the release of 2 de novo
      created peptides ABri and ADan, the main components of amyloid fibrils in these
      inherited dementias. Although the molecular mechanisms and signal transduction
      pathways elicited by the amyloid deposits and their relation to cognitive
      impairment remain to be clarified, new evidence indicates that, independent of
      the differences in their primary structures, Abeta, ABri, and ADan subunits are
      able to form morphologically compatible ion-channel-like structures and elicit
      single ion-channel currents in reconstituted lipid membranes. These findings
      reaffirm the notion that non-Abeta amyloidosis constitute suitable alternative
      models to study the role of amyloid deposition in the mechanism of neuronal cell
      death.

PMID- 16612985
TI  - Modeling familial British dementia in transgenic mice.
AB  - The chromosome 13 linked amyloidopathies familial British dementia (FBD) and
      familial Danish dementia (FDD) are caused by mutations in the C-terminus of the
      BRI2 gene. In both diseases, novel peptides are deposited in amyloid plaques in
      the brain. Several laboratories have attempted to model these diseases in BRI2
      transgenic mice with limited success. While high expression levels of BRI protein
      were achieved in transgenic lines, no ABri-amyloidosis was observed in aged mice.
      This review discusses the strategies chosen and problems experienced with the
      development of FBD/FDD models and suggests novel approaches to model the diseases
      in murine models.

PMID- 16612986
TI  - Supratentorial primitive neuroectodermal tumor (sPNET).

PMID- 16612987
TI  - A 21-year-old female with a third ventricular tumor.
AB  - A 21-year-old female presented with a 2-months history of tinnitus, vertigo and
      nausea. On magnetic resonance imaging of the brain, she demonstrated a small
      contrast-enhancing mass in the posterior part of the third ventricle.
      Intraoperatively, the tumor showed a close relationship to the choroid plexus of
      the third ventricle. Histopathology revealed a benign schwannoma of World Health
      Organization grade I. To our knowledge, only 9 cases of intraventricular Schwann
      cell tumors have been published so far. Most of these tumors were benign
      schwannomas, except for 2 cases of malignant peripheral nerve sheath tumors. The
      tumor of our patient is the first reported schwannoma of the third ventricle. The
      origin of intraventricular Schwann cell tumors is unknown. They may arise from
      autonomic perivascular nerves in the choroid plexus or from ectopic neural crest
      derived cells. Histologically, intraventricular schwannoma needs to be
      distinguished from other spindle cell tumors, in particular pilocytic astrocytoma
      and fibroblastic meningioma.

PMID- 16612988
TI  - 45-year-old male with symptomatic mass in the frontal lobe.
AB  - A 45-year-old male patient developed focal seizures in his right arm.
      Neuroimaging demonstrated a tumor of the left frontal lobe. Tumor classification
      was undecided after stereotactic biopsy. Neuropathological examination of the
      open biopsy specimen revealed overlapping morphological features of an
      oligodendroglioma and a central neurocytoma. Groups of tumor cell featured the
      typical "fried egg" appearance seen in oligodendroglioma; microcalcifications and
      a network of branching non-proliferating vessels were present. Neurocytoma-like
      features included small nucleus-free areas of neuropil and perivascular
      pseudorosettes. Neuron specific enolase was strongly expressed cytoplasmically in
      the tumor cells and the "neuropil islands" were found to express synaptophysin.
      The final diagnosis of an oligodendroglioma with neurocytic differentiation was
      based on tumor location, clinicopathological findings and diagnostic genotyping.
      Combined loss of heterozygosity (LOH) on the short arm of chromosome 1 (1p) and
      the long arm of chromosome 19 (19q), the "molecular signature" of
      oligodendrogliomas, was revealed. Besides supporting the diagnosis of an
      oligodendroglioma, the molecular data allow for additional therapeutic options.
      These tumors may point to the presence of yet another potential tumor precursor
      cell similar to the recently discovered "N-O"-cells in the cerebral cortex of
      rats, capable of differentiation into neurons and oligodendrocytes.

PMID- 16612990
TI  - Introduction to medical anthropology in the Muslim world.

PMID- 16612989
TI  - A 43-year-old woman with a temporal mass.
AB  - A 43-year-old woman with a past medical history of breast cancer and an acute
      myeloid leukemia (AML) presented with headache over a 3-week period. The clinical
      examination was completely unremarkable. CT and MRI scans showed a contrast
      enhancing lesion in the left temporal lobe. Histopathologic examination revealed
      a malignant, hematopoietic tumor with high mitotic activity, areas of necrosis
      and diffuse infiltration of the brain parenchyma. Positive staining for
      Chloroacetateesterase and lysozyme of tumor cells identified its myeloid lineage.
      The diagnosis was granulocytic sarcoma (GS)/chloroma, a metastatic manifestation
      of AML. Granulocytic sarcoma (GS) most often occurs in patients with AML,
      myelodysplastic syndromes and myeloproliferative disorders, and can involve any
      organ. However intracerebral manifestation of GS is a rare event. In this case
      histopathological features and differential diagnoses of intracerebral GS are
      discussed.

PMID- 16612991
TI  - On the politics and practice of Muslim fertility: comparative evidence from West
      Africa.
AB  - Recent popular works have represented Muslim fertility as dangerously high, both
      a cause and consequence of religious fundamentalism. This article uses
      comparative, statistical methods to show that this representation is empirically
      wrong, at least in West Africa. Although religion strongly inflects reproductive
      practice, its effects are not constant across different communities. In West
      African countries with Muslim majorities, Muslim fertility is lower than that of
      their non-Muslim conationals; in countries where Muslims are in the minority,
      their apparently higher reproductive rates converge to those of the majority when
      levels of education and urban residence are taken into account. A similar pattern
      holds for infant mortality. By contrast, in all seven countries, Muslim women are
      more likely to report that their most recent child was wanted. The article
      concludes with a discussion of the relationship between autonomy and fertility
      desires.

PMID- 16612992
TI  - Reproductive strategies and Islamic discourse: Malian migrants negotiate everyday
      life in Paris, France.
AB  - Approximately 37 thousand Malians currently reside in France as part of the West
      African diaspora. Primarily Muslim, both women and men confront challenges to
      their understandings of Islamic prohibitions and expectations, especially those
      addressing conjugal relations and reproduction. Biomedical policies generate
      marital conflicts and pose health dilemmas for women who face family and
      community pressures to reproduce but biomedical encouragement to limit
      childbearing. For many women, contraception represents a reprieve from repeated
      pregnancies and fatigue in spite of resistance from those who contest women's
      reproductive decisions as antithetical to Islam. French social workers play a
      particularly controversial role by introducing women to a discourse of women's
      rights that questions the authority of husbands and of religious doctrine. Women
      and men frame decisions and debate in diverse interpretations of Islam as they
      seek to manage the contradictions of everyday life and assert individual agency
      in the context of immigration and health politics.

PMID- 16612993
TI  - "Fewer children, better life" or "as many as God wants"? Family planning among
      low-income Iranian and Afghan refugee families in Isfahan, Iran.
AB  - In the West it is often assumed that religion (esp. Islam) and contraception are
      mutually exclusive. Yet, the Islamic Republic of Iran has one of the most
      successful family-planning programs in the developing world, and is often looked
      to as a potential model for other Muslim countries. Although Iran's family
      planning program has been extremely successful among Iranians, it has been far
      less successful among Afghan refugees and other ethnic groups. Afghans and
      Iranians both seek services in Iran's public health sector for family health
      care, treatment of infectious disease, and childhood vaccinations. On these
      occasions, all adult married patients are strongly encouraged to use family
      planning to reduce the number of offspring. In this article, we explore how
      Iran's family-planning program is differentially perceived and utilized among low
      income Iranian and Afghan refugee families in rural and urban locations.
      Particular attention is given to how different interpretations of Islam may or
      may not influence reproductive health-related behaviors and how cultural factors
      influence reproductive strategies.

PMID- 16612994
TI  - Bleeding babies in Badakhshan. Symbolism, materialism, and the political economy
      of traditional medicine in post-Soviet Tajikistan.
AB  - The bleeding of infants via the skin (pile) and the roof of the mouth (qum) is
      practiced in Badakhshan, the easternmost province of Tajikistan. Like folk
      practices elsewhere, pile and qum exist at the interstices of modern society and
      reflect a complex religious, historical, and social response to poverty,
      marginality, and the global processes associated with the collapse of the Soviet
      Union. In this article, I attempt to move beyond an ethnomedical analysis by
      examining these bloodletting practices in the context of their contemporary
      meaning, as a moral response to suffering and to the social changes that have
      taken place in the post-Soviet period.

PMID- 16612995
TI  - "He won't be my son": Middle Eastern Muslim men's discourses of adoption and
      gamete donation.
AB  - In the Sunni Muslim world, religious mandates prohibit both adoption and gamete
      donation as solutions to infertility, including in the aftermath of in vitro
      fertilization (IVF) failures. However, both of these options are now available in
      two Middle Eastern countries with significant Shi'ite Muslim populations (Iran
      and Lebanon). On the basis of fieldwork in multisectarian Lebanon, I examine in
      this article attitudes toward both adoption and gamete donation among childless
      Muslim men who are undertaking IVF with their wives. No matter the religious
      sect, most Muslim men in Lebanon continue to resist both adoption and gamete
      donation, arguing that such a child "won't be my son". However, against all odds,
      some Muslim men are considering and undertaking these alternatives to family
      formation as ways to preserve their loving marriages, satisfy their fatherhood
      desires, and challenge religious dictates, which they view as out of step with
      new developments in science and technology. Thus, in this article I examine the
      complicated intersections of religion, technology, marriage, and parenthood in a
      part of the world that is both poorly understood and negatively stereotyped,
      particularly in the aftermath of September 11, 2001.

PMID- 16612996
TI  - Sexuality issues in the movement to abolish female genital cutting in Sudan.
AB  - Ethnographic research in seven rural Sudanese communities in 2004 demonstrates
      the deep association between infibulation and expectations for successful male
      sexual response, reinforced by aesthetic values about the preferred body form for
      females. In contrast, women conceive of the uninfibulated body as lacking in both
      propriety and beauty, as well as making a woman less able to please a husband
      sexually. Female sexual response has only recently begun to be discussed in the
      context of change efforts to end female genital cutting.

PMID- 16612997
TI  - [Radiation medicine and its significance to scientific and practical internist's
      activity].
AB  - The author of the article analyzes the significance of radiation medicine in the
      system of medical sciences, and stresses that radiation medicine and other fields
      of medicine have a lot of common points in their interests and the ways of
      development. All these points concern patients and problems of the evaluation of
      their health status in connection with diverse forms of radiation contacts. The
      author discusses the reliability of the sources of information and the forms of
      data presentation in the main publications addressed to certain groups of medical
      practitioners, researchers, and healthcare managers. The most significant results
      of radiation medicine, which may be useful to clinical medicine in general, are
      summarized in the article. The author annotates and assesses the targeting of
      manuals of radiobiology and radiation medicine issued in the resent years.

PMID- 16612998
TI  - [Atrial fibrillation (the questions of etiology, classification, and treatment)].
AB  - The issue of atrial fibrillation is covered in the article in detail; the
      frequency of its individual forms is presented. The systematization of the
      individual forms of atrial fibrillation, the pathogenesis of its various forms,
      their reversibility and constancy are given from up-to-date positions. The author
      adduces a detailed description of modern methods of pharmacotherapy and
      instrumental therapy.

PMID- 16612999
TI  - [The incidence and primary multiplicity of colon cancer].
AB  - Analysis of Moscow cancer register demonstrates a steady growth of colon cancer
      (CC) incidence and mortality in Moscow, also noted in all large industrial cities
      of economically developed countries. In Moscow between 1996 and 2001, the
      incidence of CC had grown 1.5 times (from 19.6 up to 30% per 100,000), and the CC
      related mortality had grown twice (from 9.1 up to 19.5% per 100,000). The
      incidence of CC among women is 1.5 to 2 times higher than that among men. The
      burst of CC incidence is noted after age 55, and the peak incidence is noted at
      age 65. Not rare (2.9% of cases) are tumors that develop simultaneously in
      different divisions of the colon, which are diagnosed during the surgery or are
      omitted even then. Such synchronous large bowel tumors are found mostly in
      patients over 60. The analysis show that metachronous tumors (3.4% of cases)
      usually develop in the colon 8 to 10 years after the first surgery for CC, or
      some other cancer, and are found mostly in patients over 70. Unlike foreign
      statistics on multicentric CC cancer, according to which primary-multiple
      (synchronous and metachronous) cancers occur in 1.24 to 14% of cases, Moscow
      statistics demonstrate a lower likelihood of such a pathology in Muscovites. To
      sum up, patients who underwent treatment for CC or any other cancer should keep
      being under an oncologist's observation due to the likelihood of the development
      of a metachronous colon tumor 8 to 10 years later.

PMID- 16613000
TI  - [Diagnostics and differential diagnostics of bronchial asthma and chronic
      obstructive pulmonary disease].
AB  - The subjects of the study were 14 patients with bronchial asthma (BA) and 11
      patients with chronic obstructive pulmonary diseases (COPD). A special diagnostic
      approach, including spirography with a broncholytic test after inhalation loading
      (IL), was developed and applied to these patients in order to optimize
      diagnostics and differentiation diagnostics of BA. IL included the use of
      hypertonic sodium chloride solution inhalation. The control group consisted of 10
      patients with non-obstructive chronic bronchitis and 22 healthy individuals. The
      results show that bronchial reaction to IL is different in patients with BA and
      COPD, and demonstrate that this diagnostic approach is appropriate when
      evaluating the peculiarities of bronchial patency. This allows more accurate
      diagnostics and differential diagnostics of BA and COPD, optimization of patient
      grouping for scientific studies, including genetic ones, and is interesting from
      the perspective of therapy prediction in patients with these diseases.

PMID- 16613001
TI  - [The clinicofunctional characterization of the phenotypes of severe
      uncontrollable bronchial asthma].
AB  - The aim of the study was to compare the clinical characteristics and the
      inflammatory process activity in the airway of patients with severe therapy
      sensitive and therapy-resistant bronchial asthma (TSBA; TRBA). The subjects were
      171 patients with severe bronchial asthma (BA) aged 18 to 60; the diagnosis was
      established prior to the study according to GINA 2002 criteria. There were 50
      TSBA patients, 121 TRBA, and 50 controls. According to a range of criteria, BA in
      TRBA was more severe than that in TSBA. TRBA patients displayed significantly
      higher indices of inflammatory process activity, such as absolute and relative
      number of eosinophiles and neutrophiles in induced sputum (IS), and IS level of
      IL-5. Evaluation of IS inflammatory markers in patients with severe BA allowed
      substantiation of the central role of persistent inflammation as a risk factor of
      TRBA development.

PMID- 16613002
TI  - [Endothelial dysfunction and risk factors in coronary heart disease].
AB  - The subjects of the study were 64 patients with coronary heart disease, and 38
      healthy individuals. In order to evaluate the degree of endothelial dysfunction
      (ED) reactive hyperemia test was performed; the degree of the relative increase
      of the brachial artery diameter, and the level of desquamated endothelial cells
      circulating in blood (CEC) were used as criteria of this dysfunction. Only in
      6.5% of the controls signs of ED (endothelium-dependent vasodilatation (EDVD)
      less than 10% and the number of CEC being greater than 5 in the field of vision)
      was noted. In group II the signs of ED were registered in 40% of patients, in
      group III--in 59% of patients (p < 0.05). In patients with no standard risk
      factors or with only one of them, both tests revealed no signs of ED, while the
      presence of 4 or more risk factors lead to a 6-fold increase of the relative
      frequency of ED.

PMID- 16613004
TI  - [Local myocardial contractility in patients with coronary heart disease and
      chronic heart failure].
AB  - The aim of the study was to evaluate the peculiarities of local left and right
      ventricular myocardial contractility in patients with coronary heart disease
      (CHD) and various degrees of chronic heart failure (CHF) using biventricular
      radioventriculography (RVG). Local left and right ventricular myocardial
      contractility was evaluated in 127 patients with CHD and CHF using RVG with a
      standard procedure of segmentary and phase histogram analysis. The patients were
      divided into two groups according to left ventricular ejection fraction (LVEF).
      Group I consisted of 89 CHD patients with NYHA II-III CHF and LVEF of > 40%;
      group II included 38 CHD patients with NYHA III-IV CHF and LVEF of < 40%. The
      significant decrease of LVEF in group II was caused by the prevalence of hypo-
      and akinetic segments in the structure of local contractility. In both groups
      total LVEF was maintained by lateral wall segments. Right ventricular
      contractility in patients with CHD and CHF was maintained by anteroseptal
      segments.

PMID- 16613003
TI  - [The cell immunity parameters in patients with acute coronary syndrome].
AB  - The subjects of the study were 75 patients with instable angina (IA) and 16
      patients with chronic coronary heart disease (CHD) following transcutaneous
      transluminal balloon angioplasty (TTBA). Their examination included the
      evaluation of the changes of some cell immunity parameters, such as the levels of
      interleukins IL-1, IL-6, and IL-10, tumor necrosis factor alpha (TNFalpha), and
      serum neopterin (NEOP), the measurement of C-reactive protein level, the
      detection of certain viral agents in blood (herpes simplex virus (HSV),
      cytomegalovirus, Chlamydia pneuoniae) using polymerase chain reaction (PCR), The
      study revealed such signs of cell immunity disbalance as the pronounced
      activation of pro-inflammatory factors (IL-6, TNFalpha, and serum NEOP). Along
      with no changes of the activity of anti-inflammatory factors (IL-10), the
      research revealed the similar direction of immune shifts in IA patients and CHD
      patients who had no clinical signs of exacerbation and had undergone TTBA. Most
      patients displayed signs of persistent viral infection, which was HSV in the
      majority of cases.

PMID- 16613005
TI  - [The rhythms of arterial pressure and heart rate in individuals with arterial
      hypertension under the conditions of Far North].
AB  - The circadian and ultradian rhythms of blood pressure (BP) and heart rate (HR)
      were studied by means of 24-hour BP monitoring in patients with arterial
      hypertension (AH) and practically healthy people working in Far North shifts. The
      subjects were 418 men. The main group consisted of 177 men aged 18 to 59 working
      in trans-polar shifts in Yamburg, Tyumen region, latitude 57 North. The
      comparison group included 158 residents of a moderate climatic zone (Tyumen,
      latitude 57 North). The control group consisted of 83 practically healthy men, of
      whom 43 worked in Far North shifts, and 40 were residents of Tyumen. The groups
      were comparable by age, AH duration, and office systolic and diastolic BP (SBP;
      DBP). The study demonstrates that even healthy people working in Far North shifts
      display high BP variability and the decrease of the stability and power of SBP,
      DBP and HR circadian rhythms due to the reduction of the amplitude, contribution
      of the rhythm to the total variability, and the increase of the amplitude of high
      frequency harmonics of the spectrum (a manifestation of extracircadian
      dissemination), which may be a sign of accelerated ageing and biological age
      increase, and may facilitate AH development. Development of AH under the extreme
      conditions of Far North shifts, unlike the conditions of moderate climatic zones,
      is accompanied by progressive BH variability increase, the worsening of the
      chronological structure of SBP and DBP, the increase of extracircadian
      dissemination, which can be of both clinical and prognostic significance.

PMID- 16613006
TI  - [The peculiarities of renal lesion in nodular polyarteritis].
AB  - Analysis of the medical records of 122 patients with nodular polyarteritis showed
      that the most frequent visceral manifestations were renal (93.4%), cardial (72%),
      and gastrointestinal (57.4%) ones. Central nervous system (CNS), pulmonary, and
      peripheral arterial lesions were less frequent (36.8%, 17.2%, and 6.6%,
      respectively). Renal lesions were manifested by arterial hypertension (AH) in 107
      patients, urinary syndrome in 97, nephrotic syndrome in 7, and rapidly
      progressing glomerulonephritis in 5 patients. Monofactor analysis revealed the
      following predictors of poor prognosis: malignant AH, nephrotic proteinuria, male
      sex, body mass reduction, intestinal ulcers, gastrointestinal hemorrhage, CNS
      lesion, heart failure, and pulmonary lesion. The relative risk of lethal outcome
      was the highest in nephrotic proteinuria (3.5) and malignant AH (2.9). In 56% of
      cases death was caused by cardiovascular complications, in 18%--chronic renal
      failure, in 11%--abdominal complications.

PMID- 16613007
TI  - [An AT-II blocker in patients with type II diabetes and arterial hypertension].
AB  - The subjects of the study were 30 patients with type II diabetes mellitus and
      mild or moderate arterial hypertension. Clinical-and-hemodinamic organoprotective
      effects of eprosartan, a new angiotensin II blocker, was evaluated in these
      patients within 16 weeks. The study found a good hypotensive effect of
      monotherapy with eprosartan in a mean therapeutic dose of 600 mg/day--the target
      blood pressure levels were achieved in 63.3% of the patients. Fasting insulin
      level and insulin resistance decreased, which improved hydrocarbonate and lipid
      exchange parameters. Eprosartan was significantly effective as an
      organoprotective agent: the patients displayed improvement of eye ground vessel
      condition, decrease of microalbuminuria, improvement of cardiodynamic parameters
      i.e. decrease of the thickness of left ventricular (LV) back wall and
      intravenricular septum, as well as reduction of myocardial mass index. 70% of the
      patients demonstrated improvement of LV diastolic function.

PMID- 16613008
TI  - [Antibiotics in pancreatology: pros and contras].
AB  - The problems of antibioticotherapy in patients with pancreatic diseases and
      pancreonecrosis in the first place, are discussed in the article in detail. The
      paper covers the indications and contraindications, as well as the most
      preferable classes of antibiotics according to bacterial flora present. The
      authors have developed a classification of medications as possible agents
      provoking pancreatitis.

PMID- 16613009
TI  - [The influence of low-intensive laser therapy on the aggregation properties of
      thrombocytes in patients with peptic ulcer].
AB  - The purpose of the study was to evaluate the influence of low-intensive laser
      therapy (LILT) on the aggregation properties of thrombocytes in patients with
      exacerbation of peptic ulcer (PU). The subjects, 111 patients aged 18 to 63, were
      divided into two groups: the main group (n = 81), and the control group (n = 30).
      In addition there were 15 healthy people who also underwent examination. Patients
      in the main group received complex treatment with untiulcer drugs and different
      methods of laser therapy: intravenous laser irradiation of blood, cutaneous
      irradiation, and a combination of both. The control group was treated with drugs
      only. The study found various changes in the aggregation properties of
      thrombocytes in patients with PU exacerbation, which consisted mostly in
      hyperaggregation. LILT had a normalizing effect on the aggregation properties of
      thrombocytes in patients of the main group.

PMID- 16613010
TI  - [Ambulatory blood pressure monitoring in the diagnostics of arterial hypertension
      associated with nephroptosis].
AB  - Nephroptosis, associated with renal circulatory disorder, is one of the reasons
      for symptomatic arterial hypertension (AH). An obvious dependence of blood
      pressure (BP) level on the body position is a feature of this form of AH.
      However, this correlation is not always easy to reveal when performing a routine
      physical examination. The authors of the article adduce 2 clinical observations
      in which ambulatory BP monitoring became the key method that allowed assuming
      dynamic vasorenal AH.

PMID- 16613011
TI  - [Decision-making in a physician's practice].
AB  - The article covers modern principles of the decision-making method, used in
      medicine and gastroenterology, in particular. These principles are based upon
      taking into consideration psychosocial features of a doctor and a patient, types
      of doctor's thinking and pathologic processes, as well as the effect of a range
      of negative factors, such as conformism, engageness of a doctor, neurotism etc.
      The author pioneers the treatment of decision-making in medicine.

PMID- 16613012
TI  - [Hiatus hernia and gastroesophageal reflux disease as a manifestation of a newly
      revealed hypothyroidism].
AB  - The aim of the study was to reveal hypothyroidism (HT) in patients with hiatus
      hernia (HH), treated at Russian Centre of Functional Surgical Gastroenterology.
      The subjects were 64 women: 18--with HH and diffuse or diffuse nodular goiter, 36
      -with HH, and 10--without endocrine or somatic disease background. The
      examination included the evaluation of the thyroid and metabolic status,
      endoscopy, and 24-hour ph-metry. The results show that one of the early signs of
      HT is HH and gastroesophageal reflux disease. The latter in HT patients is
      associated with gastrointestinal motor-evacuatory disturbances rather than with
      acid exposition in the distal esophagus.

PMID- 16613013
TI  - When do people visit a doctor?
AB  - We examine the length of time between when an individual feels sick and when
      he/she visits a doctor using survival analysis to capture the dynamic aspects of
      this behavior. If the disease is light, actions such as OTC medicine or sick
      leave are alternatives to visiting a clinic or a hospital immediately. The timing
      of the visit depends only the person's decision, not on a doctor's, so we can
      limit discussion to the effect of ex-post moral hazard excluding physician
      induced demand. Participants were asked to keep a log of illness-related behavior
      such as dates of episodes, subjective symptoms, sick leaves, and medical
      treatment at hospitals. Neither the copayment rate nor access cost had a
      significant effect on the behavior of visiting a doctor, whereas available
      alternatives delay the timing of a visiting. Severe symptoms and fever hastened
      the time. The results suggest that the traditional argument about ex-post moral
      hazard is somewhat misleading.

PMID- 16613014
TI  - Modelling the redistribution of hospital supply to achieve equity taking account
      of patient's behaviour.
AB  - Policies that seek to achieve geographic equity in countries with a National
      Health Services (NHS) require information on how to change the distribution of
      supply to achieve greater equity in access and utilisation. Previous methods for
      analysing the impact of hospital changes have relied on crude assumptions on
      patients' behaviour in using hospitals. The approach developed in this study is a
      multi-modelling one based on two mathematical programming location-allocation
      models to redistribute hospital supply using different objective functions and
      assumptions about the utilisation behaviour of patients. These models show how
      different policy objectives seeking equity of geographic access or utilisation
      produce different results and imply trade-offs in terms of reduction in total
      utilisation.

PMID- 16613015
TI  - Stochastic bed balancing of an obstetrics hospital.
AB  - Health care is one of the largest industries in the developed world and the top
      domestic industry in the United States (US). Over the past thirty years there has
      been a dramatic increase in healthcare costs in the US, of which about one-third
      can be attributed to hospital spending. One of the key factors in hospital cost
      containment and revenue enhancement is effective and efficient bed planning and
      capacity analysis. This study aims to balance bed unit utilizations across an
      obstetrics hospital and minimize the blocking of beds from upstream units within
      given constraints on bed reallocation. The methodology includes the assessment
      and effect of time-dependent patterns of monthly, daily, and hourly demand.
      Queuing networks are first used to assess the flows between units, establish
      target utilizations of bed units, and involve stakeholders in a flow
      characterization that they understand. Discrete-event simulation is then used to
      maximize the flow through the balanced system including non-homogeneous effects,
      non-exponential lengths of stay, and blocking behavior. Results of the models are
      validated against actual data collected from the hospital. Several 'what if'
      scenarios are studied showing that 38% more patient flow can be achieved with
      only 15% more patient beds. The results of the study have been implemented.

PMID- 16613016
TI  - Designing appointment scheduling systems for ambulatory care services.
AB  - The current climate in the health care industry demands efficiency and patient
      satisfaction in medical care delivery. These two demands intersect in scheduling
      of ambulatory care visits. This paper uses patient and doctor-related measures to
      assess ambulatory care performance and investigates the interactions among
      appointment system elements and patient panel characteristics. Analysis
      methodology involves simulation modeling of clinic sessions where empirical data
      forms the basis of model design and assumptions. Results indicate that patient
      sequencing has a greater effect on ambulatory care performance than the choice of
      an appointment rule, and that panel characteristics such as walk-ins, no-shows,
      punctuality and overall session volume, influence the effectiveness of
      appointment systems.

PMID- 16613017
TI  - Determinants of hospital loss in Thailand: experience from the first year of a
      universal coverage health insurance program.
AB  - The objective of this study was to examine determinants of hospital loss in
      Thailand. Administration national data for 640 public hospitals of fiscal year
      2002 from Ministry of Public Health were analyzed. Results showed that various
      managerial, service mix, and market variables were significantly associated with
      the likelihood of the hospital being unprofitable. Hospital characteristics were
      associated with the amount of loss. The results also suggested that managing the
      number of hospital employees, inventory, and patient hospitalization could
      control the amount of loss. In conclusion, most of identified factors associated
      with hospital loss were manageable. The ramification of this study was to help
      policy makers understand the hospital loss situation in Thailand after
      implementing the UC scheme and design policy to resolve the hospital loss
      problems.

PMID- 16613018
TI  - Incremental changes in the workforce to accommodate changes in demand.
AB  - In many service organizations, rosters must be constructed weekly or monthly as
      demand and available personnel change. Once the permanent workforce is fixed, it
      may not be possible to alter its composition easily, implying that expensive
      contract labor may be the only option to cover shortages. With respect to nursing
      resources, this means calling in part-timers, casuals, or agency nurses on a
      daily basis, or hiring travelers for up to several months at a time. This paper
      addresses the latter option and presents two models that can be used to solve
      what we call the nurse addition problem. The first was originally developed to
      solve the midterm preference scheduling problem and is based on a pattern-view
      formulation. The second is derived from a shift-view formulation and is solved
      with a branch-and-price algorithm. In either case, the objective is to hire up to
      some predetermined number of nurses and assign them midterm schedules that
      minimize the maximum amount of uncovered shifts per day in the planning horizon.
      Each roster selected for a new nurse must satisfy a set of hard constraints
      related to the total working hours, workstretches, time between shifts, and
      weekend requirements, and a set of soft constraints related

PMID- 16613019
TI  - Impact of surgical sequencing on post anesthesia care unit staffing.
AB  - This paper analyzes the impact of sequencing rules on the phase I post anesthesia
      care unit (PACU) staffing and over-utilized operating room (OR) time resulting
      from delays in PACU admission. The sequencing rules are applied to each surgeon's
      list of cases independently. Discrete event simulation shows the importance of
      having a sufficient number of PACU nurses. Sequencing rules have a large impact
      on the maximum number of patients receiving care in the PACU (i.e., peak of
      activity). Seven sequencing rules are tested, over a wide range of scenarios. The
      largest effect of sequencing was on the percentage of days with at least one
      delay in PACU admission. The best rules are those that smooth the flow of
      patients entering in the PACU (HIHD (Half Increase in OR time and Half Decrease
      in OR time) and MIX (MIX OR time)). We advise against using the LCF (Longest
      Cases First) and equivalent sequencing methods. They generate more over-utilized
      OR time, require more PACU nurses during the workday, and result in more days
      with at least one delay in PACU admission.

PMID- 16613020
TI  - A note on health care productivity with uncertain data.
AB  - The present paper suggests extending the FDH-method, known from the efficiency
      measurement literature, to cover interval production data. Interval data
      represent a direct way to handle data uncertainty and problems with data
      comparability which seem particularly prevalent concerning health care
      applications. We illustrate the method using a simple 1-input-2-output model on
      health care data from the OECD health statistics.

PMID- 16613021
TI  - Development of a computed tomographic calibration method for the determination of
      lean meat content in pig carcasses.
AB  - Sixty left sides of pig carcasses were scanned by spiral computed tomography (CT)
      to measure lean meat weight and percentage. The carcasses were fully dissected
      and scanned to develop a calibration protocol. Different image analyses were
      performed on the basis of anatomically defined scans, direct volumetric
      estimation, body- and grey-scale ranges and using Partial Least Squares (PLS)
      regression of data provided by CT. The R2 values of the calibrations for lean
      meat weight were 0.874, 0.976, 0.983 and 0.992, respectively, depending on the
      method applied. The PLS proved to be the best approach with a calibration RSD of
      232 g. When changing from lean meat weight to percentage, the statistical
      goodness drops-to a very small extent (R2 = 0.988, RSD = 0.56). According to the
      results, the CT method can be recommended as a reference for determining the lean
      meat content of pig carcasses.

PMID- 16613022
TI  - Plasmid profiles of virulent Rhodococcus equi isolates from soil environment on
      horse-breeding farms in Hungary.
AB  - The plasmid profiles of virulent Rhodococcus equi strains isolated on three horse
      breeding farms located in different parts of Hungary were investigated. From 49
      soil samples collected on the three farms, 490 R. equi isolates (10 from each
      sample) were obtained and tested for the presence of 15- to 17-kDa antigens
      (VapA) by immunoblotting and PCR. Ninety-eight VapA-positive isolates were
      detected from 30 of the 49 culture-positive samples with a prevalence ranging
      from 13.1% to 23.2%. Of the 98 virulent isolates, 70 contained an 85-kb type I
      plasmid, 13 contained an 87-kb type I plasmid, and 15 contained an 85-kb type III
      plasmid which had been uniquely isolated from soil isolates in the United States.
      This study demonstrates that the virulent form of R. equi is very widespread in
      the soil environment of these stud farms in Hungary and the plasmid pattern is
      different from farm to farm.

PMID- 16613023
TI  - Clinicopathological changes and effect of imidocarb therapy in dogs
      experimentally infected with Babesia canis.
AB  - In this study one spleen-intact dog (A) and two splenectomised dogs (BSE, CSE)
      were infected with Babesia canis. All animals developed an acute disease
      characterised by fever, haemoglobinuria and anaemia, the latter being more severe
      in the splenectomised dogs. Fever and parasitised red blood cells were detected
      for three days after imidocarb treatment in the splenectomised animals.
      Haematological abnormalities included regenerative anaemia, thrombocytopenia and
      leukopenia (due to neutropenia and lymphopenia) in the acute phase, soon followed
      by leukocytosis, neutrophilia and left shift a few days later. Acute hepatopathy
      was detected in all dogs with elevated ALT activity, which was more seriously
      altered in the splenectomised dogs. Diffuse changes in liver structure and
      hepatomegaly were seen by ultrasonography. Liver biopsy and histology revealed
      acute, non-purulent hepatitis in the splenectomised dogs. Both splenectomised
      dogs were successfully cured after collection of 400 ml highly parasitised blood,
      proving that large-amount antigen production is possible with rescuing the
      experimental animals. Whole blood transfusion, imidocarb and supportive care with
      infusions, antipyretics, glucocorticoids and diuretics were applied. The spleen
      intact dog clinically recovered after receiving supportive treatment, with no
      imidocarb therapy. Microbial infections developed in both splenectomised animals
      (BSE: haemobartonellosis, CSE: osteomyelitis caused by Escherichia coli),
      probably as a consequence of immunosuppression after splenectomy and
      glucocorticoid therapy.

PMID- 16613024
TI  - Electroencephalographic and electromyographic changes during the use of
      detomidine and detomidine-butorphanol combination in standing horses.
AB  - Clinically, the use of detomidine and butorphanol is suitable for sedation and
      deepening of analgosedation. The aim of our study was to establish the influence
      of detomidine used alone and a butorphanol-detomidine combination on brain
      activity and to evaluate and compare brain responses (using
      electroencephalography, EEG) by recording SEF90 (spectral edge frequency 90%),
      individual brain wave fractions (beta, alpha, theta and delta) and
      electromyographic (EMG) changes in the left temporal muscle in standing horses.
      Ten clinically healthy cold-blooded horses were divided into two groups of five
      animals each. Group I received detomidine and Group II received detomidine
      followed by butorphanol 10 min later. SEF90, individual brain wave fractions and
      EMG were recorded with a pEEG (processed EEG) monitor using computerised
      processed electroencephalography and electromyography. The present study found
      that detomidine alone and the detomidine-butorphanol combination significantly
      reduced SEF90 and EMG, and they caused changes in individual brain wave fractions
      during sedation and particularly during analgosedation. The EMG results showed
      that the detomidine-butorphanol combination provided greater and longer muscle
      relaxation. Our EEG and EMG results confirmed that the detomidine-butorphanol
      combination is safer and more appropriate for painless and non-painless
      procedures on standing horses compared to detomidine alone.

PMID- 16613025
TI  - Atmospheric flash injuries in roe deer (Capreolus capreolus).
AB  - The pathological and histopathological examination of two female roe deer found
      dead after a severe thunderstorm is described. One of the two roe deer was killed
      by a direct hit of atmospheric flash, while the other animal, lying 1.5 m from
      the first one, died as a consequence of ground current strike. The major part of
      the coat and skin of the animal that was killed by a direct hit was covered with
      scorched streaks. The trachea and bronchi of both animals contained a
      considerable amount of aspirated light-red foam. Necropsy revealed diffuse
      haemorrhages over the epicardium of the right atrium with a diameter of 1
      millimetre. The liver and the kidney exhibited severe congestion.

PMID- 16613026
TI  - Molecular diagnosis of avian nephritis: preliminary report.
AB  - Kidney samples from chickens diagnosed with acute nephritis and gout were
      subjected to histological and electron microscopic examination. The
      investigations revealed cytoplasmic inclusion bodies in the tubular epithelial
      cells containing round virions of about 30 nm in diameter. Since avian nephritis
      virus (ANV) is known as a potential causative agent of the so-called baby chick
      nephropathy, an RT-PCR assay was developed for the molecular detection of ANV
      specific nucleic acid in the specimen. The specificity of the assay was confirmed
      by direct sequencing of the amplicon obtained in the reaction. The nucleotide
      sequence of the PCR product showed 92% identity with the reference ANV sequence
      deposited in the GenBank database. After having been validated on some other
      suspicious cases of avian nephritis, the PCR method described in this study can
      be a potential tool for routine diagnostic examination of samples submitted from
      cases of gout and nephropathy in chickens.

PMID- 16613027
TI  - The role of copepods (Cyclops spp.) in eliminating the actinospore stages of fish
      parasitic myxozoans.
AB  - The actinospore consumption of copepods (Cyclops spp.) was demonstrated by
      laboratory observations. It was observed that in experimental dishes the number
      of actinospores floating in the water decreased, or such actinospores were
      completely eliminated, in the presence of copepods. The ingestion of actinospores
      by copepods and their further fate were monitored by fluorescent staining and by
      conventional histological techniques. The actinospores were observed to have got
      caught on the filters of Cyclops spp. Two and a half hours after the copepods had
      been placed into water containing actinospores, their digestive tract was found
      to contain spores that had extruded their filaments from the polar capsules.
      After copepods having ingested the actinospores of the species Myxobolus
      pseudodispar had been fed to roaches, no muscle infection developed in the fish
      host. It is likely that Cyclops spp. can filter out actinospores floating in the
      water also from natural waters, thus decreasing the chance of development of
      myxosporean infections.

PMID- 16613028
TI  - Noradrenergic and cholinergic innervation of the accessory sexual glands in male
      sheep.
AB  - Immunohistochemistry was applied to determine the distribution patterns of nerve
      fibres containing tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH),
      neuropeptide Y (NPY), vasoactive intestinal peptide (VIP) and vesicular
      acetylcholine transporter (VAChT) in the prostate, seminal vesicle (SV) and
      bulbourethral glands (BU) of male sheep. In all organs studied, cholinergic
      innervation was more developed than noradrenergic innervation. Numerous VAChT
      immunoreactive (IR) nerve fibres were found in the muscular layer and mucosa of
      the SV and BU as well as in the prostate. A similar abundance of noradrenergic
      nerve fibres (showing immunoreactivity both to TH and DbetaH) was also found in
      both layers of the SV and BU (but not in the prostate). In the prostate a
      moderate density of VIP-IR nerve fibres was present but only very scarce NPY-IR
      nerve fibres were shown. All the studied accessory sexual glands (ASG) of male
      sheep contained VIP-IR nerve fibres in a similar frequency. Double
      immunohistochemistry revealed that the vast majority of noradrenergic nerve
      fibres also contained NPY. None of the noradrenergic nerve fibres showed the
      presence of VAChT or VIP. The possible functional significance of these findings
      is discussed.

PMID- 16613029
TI  - Effects of feeding a standard diet on duodenal impedancometry in pigs.
AB  - The effects of gastric feeding on intestinal motility are still under debate. In
      order to better define the character of the contractile activity in fed and
      fasting states, we used the impedance technique to investigate the duodenal time
      periods of the migrating motor complex (MMC) and the interdigestive phases I-III.
      During general anaesthesia, pigs (32-40 kg) were instrumented with a luminal
      impedance catheter into the proximal duodenum in fasting (n = 6) and fed states
      (n = 6, Muskator, 400 g, Muskator-Werk, Dusseldorf, Germany). Duodenal motility
      was recorded continuously for 4 h, which made it possible to determine the length
      of interdigestive phases I-III and the MMC cycle. Differences between the groups
      were compared by using the Wilcoxon Rank-Sum Test. Feeding patterns were only
      found in pigs in the fed state. The subsequent MMC cycle length was shortened by
      34% (p = 0.007) which was due to a shortened phase I of the MMC cycle (p =
      0.014). While phase II seemed to be unaffected, phase III was prolonged by 31%
      after feeding had occurred (p = 0.012). The present study suggests that a
      standard maintenance diet disrupts the spontaneous MMC cycles by turning into fed
      pattern with the subsequent MMC cycle length being shortened. This was mainly due
      to a shortened phase I.

PMID- 16613030
TI  - Measurement of redox potential and steroid concentrations in the follicular fluid
      of growing and regressing follicles of mares.
AB  - The aim of this study was to prove if oxidation-reduction levels in the
      follicular fluid were new functional indices of follicular health and whether
      there was a high level of accordance with endocrinological parameters and with
      the growth stage as detected by ultrasound monitoring of individual follicles
      during the oestrous cycle in mares. Follicles were classified as growing and
      regressing follicles using ultrasonography. Altogether 48 follicles with a
      diameter from 20 to 56 mm were aspirated by transvaginal ultrasound guided
      follicular aspiration. Follicular concentration of oestradiol and progesterone in
      relation to the diameter of growing follicles showed correlations of r = 0.64 and
      r = 0.57, respectively. The redox potential derived index D2 varied from -448 to
      +431 in the collected fluids of the follicles. The accordance of the judgement of
      all follicles using both complexes of methods - endocrinological and
      ultrasonographic parameters vs. analysis of oxidation and reduction levels -
      reached 72.5%. This finding has shown that parameters of redox reactions do not
      correlate closely with the stage of follicular growth or regression as determined
      by in vivo scanning of ovaries or by assessment of follicular steroid
      concentrations. However, the measurement of redox potentials offers an
      opportunity to examine the whole process of metabolism in follicular cells and to
      forecast impairments of cellular performances. Changes of redox parameters in
      growing follicles enable an earlier prediction of their further development. The
      data demonstrate that growing and regressing follicles do not represent
      nonatretic, early atretic and atretic follicles, respectively.

PMID- 16613031
TI  - Effect of open pulled straw (OPS) vitrification on the fertilisation rate and
      developmental competence of porcine oocytes.
AB  - Freezing technologies are very important to preserve gametes and embryos of
      animals with a good pedigree or those having high genetic value. The aim of this
      work was to compare immature and in vitro matured porcine oocytes regarding their
      morphology and ability to be fertilised after vitrification by the open pulled
      straw (OPS) method. In four experiments 830 oocytes were examined. To investigate
      the effect of cumulus cells on oocyte survival after OPS vitrification, both
      denuded and cumulus-enclosed oocytes were vitrified at the germinal vesicle (GV)
      stage, then after vitrification they were matured in vitro. Besides, in vitro
      matured oocytes surrounded with a cumulus and those without a cumulus were also
      vitrified. The survival of oocytes was evaluated by their morphology. After in
      vitro fertilisation the rates of oocytes penetrated by spermatozoa were compared.
      Our results suggest that the vitrification/warming procedure is the most
      effective in cumulus-enclosed oocytes (22.35 +/- 1.75%). There was no difference
      between the order of maturation and vitrification in cumulus-enclosed oocytes,
      which suggests the importance of cumulus cells in protecting the viability of
      oocytes during cryopreservation.

PMID- 16613032
TI  - Survival of mouse embryos after vitrification depending on the cooling rate of
      the cryoprotectant solution.
AB  - The aim of the study was to determine the relationship between the rate of
      cooling of eight-cell mouse embryos to the temperature of liquid nitrogen (-196
      degrees C) and their developmental capacity after thawing on the basis of their
      ability to leave the zona pellucida ('hatching') during in vitro culturing. Eight
      cell embryos were obtained from superovulated female mice and divided into three
      experimental and one control group. Embryos from the experimental groups were
      cryopreserved by the vitrification method using ethylene glycol as
      cryoprotectant. The vitrification protocols used in the study differed in the
      rate of cooling of the cryoprotectant solution. Embryos from the first group were
      frozen in conventional 0.25-ml plastic straws, those from the second group in
      pipetting 'tips', and embryos from the third group, placed in vitrification
      solution, were introduced dropwise directly into liquid nitrogen. The control
      group of embryos was cultured in vitro without freezing in a culturing medium in
      an environment consisting of 95% air and 5% CO2. The developmental capacity of
      thawed embryos was assessed on the basis of their ability to leave the zona
      pellucida ('hatching') after three days of in vitro culturing. In the control
      group 95.1% of embryos 'hatched'. A significantly higher number of embryos that
      'hatched' after thawing was observed in the group introduced dropwise directly
      into liquid nitrogen (60.0%) compared to the group frozen in pipetting 'tips'
      (37.9%). The group frozen in straws yielded significantly the lowest proportion
      of 'hatching' embryos (8.1%). These results showed that increasing cooling rates
      during vitrification of embryos improved their survival.

PMID- 16613033
TI  - Determination of carbendazim residues in the eggs, liver and pectoral muscle of
      Japanese quail (Coturnix coturnix japonica).
AB  - The effect of carbendazim, a widely applied cereal seed dressing agent, was
      studied in Japanese quail (Coturnix coturnix japonica) during an overall period
      of eight weeks, consisting of a four-week feeding phase and a subsequent four
      week excretion period. Body mass and feed consumption of the birds were monitored
      and residues of the active ingredient were determined by an analytical chemical
      method. During the eight-week study period, changes (either decrease or increase)
      directly attributable to the toxic effects of carbendazim were not found either
      in body mass or in feed consumption. Active ingredient levels exceeding the limit
      of detection were found in the liver (average: 0.0262 mg/kg) and pectoral muscle
      (average: 0.0236 mg/kg) of the birds and also in the egg (0.0338 mg/kg) samples.
      From the results it can be concluded that through the consumption of cereal seeds
      dressed with carbendazim, this active ingredient can be incorporated into the
      tissues of animals. Via the food chain, carbendazim can also enter the human
      organism, where it may cause various pathological changes in interaction with
      other chemicals.

PMID- 16613034
TI  - [Fifty years later or the way it was].

PMID- 16613035
TI  - [Combined regional anesthesia of the lower extremities in children with cerebral
      paralysis].
AB  - The authors share their first experience of combined regional anesthesia during
      surgical interventions into the lower extremities in children with infantile
      cerebral paralysis (ICP). A hundred and twenty-five blocks were performed in
      patients aged 5 to 20 years. Lidocaine, marcaine, naropine, or a mixture of
      lidocaine and marcaine mixture, were used. The paper describes the specific
      features of techniques for femoral-sciatic nerve blocks in these patients, shows
      the adequacy of anesthesia at surgery and the very good course of the
      postoperative period due to continuous analgesia and the alleviation of muscle
      spasticity in the operated limb.

PMID- 16613036
TI  - [Postoperative epidural bupivacaine infusion in pediatric oncology].
AB  - The paper presents the results of use of continuous epidural bupivacaine infusion
      for postoperative anesthesia in 88 children operated on for malignant tumors. Two
      groups of patients differing in the procedure of epidural bupivacaine infusion
      are compared. The use of bupivacaine at a higher concentration (0.25%) within the
      first 12 hours of the early postoperative period can provide a more effective
      anesthesia than that at a concentration of 0.125%. The efficacy and tolerability
      of the above procedures for injecting the local anesthetic are studied and their
      after-effects are analyzed.

PMID- 16613037
TI  - [Temperature balance and the possibility of its maintenance during general
      anesthesia in children].
AB  - The problems of hypothermia in the perioperative period, which are one of the
      most important ones in pediatric practice, in babies in particular, are solved,
      by using a broad spectrum of methods for preventing and correcting the patients'
      thermal balance. Convection heating systems exercise an on-line control over the
      baby's thermal regime during a surgical intervention and intensive care. The
      authors' own experience allows these systems to be recommended for wide practical
      application in the activities of anesthesiology and intensive care services.

PMID- 16613038
TI  - [Continuous epidural ropivacaine analgesia in adolescents].
AB  - The paper deals with the efficiency of postoperative analgesia after
      thoracoplasty in 43 adolescents with the funnel chest. Within the first 64-72
      postoperative hours, the patients received a continuous epidural infusion of 0.2%
      ropivacaine solution at a rate of 0.3 ml/kg/hr. Analyses of hemodynamic
      parameters and the pain scale demonstrated the efficiency of this postoperative
      analgesia in 74.4% of the adolescents.

PMID- 16613039
TI  - [Induction of anesthesia with halogen-containing anesthetic agents in children].
AB  - The study has comparatively evaluated the effectiveness and safety of halothane,
      enflurane, and isoflurane in children during induction. Seventy hundred and eight
      patients aged 1-14 years who had ASA I-II anesthetic risks were examined. Gas
      induction was performed as monoanesthesia through the semi-open circuit with high
      gas flow (100% O2 6 l/min) in combination with halothane (n = 236), enflurane (n
      = 236), or isoflurane (n = 236) without N2O. The authors have compared the
      following criteria: the speed and comfort of induction, the parameters of
      hemodynamics and external respiration, and the rate of adverse reactions and
      complications during induction. The studies have established that in terms of
      comfort, safety, and the rate clinical effect achievement, the drugs of choice
      for gas induction in children are enflurane and, to a lesser extent, halothane.
      Gas induction with isoflurane should not be performed in children since the agent
      rather frequently exerts an irritant action on the upper airways, which reduces
      the speed of initial narcosis and increases the likelihood of one or another
      adverse reactions; however; it has advantages as a less hemodynamic effect.

PMID- 16613040
TI  - [Use of a laryngeal mask during combined regional anesthesia in children].
AB  - For intraoperative anesthesia, the authors applied central regional blocks. A
      laryngeal mask was used to maintain free airways patency. The purpose of this
      study was to provide evidence for the effectiveness of a laryngeal mask used
      under combined regional anesthesia and to establish whether the mask could be
      employed for artificial ventilation during laparoscopy in children.

PMID- 16613041
TI  - [The early postanesthetic period in children].
AB  - Forty-one children aged 4 to 15 years, who had been operated on for varicocele
      and hernias at various sites, were examined. Central hemodynamics, and the level
      of sedation and pain were assessed. Studies were performed in 2 groups of
      patients: 1) those who received anesthesia with ketamine in combination with
      propofol and 2) those who had inhalational-mask anesthesia using phtorotan in
      combination with nitrous oxide. They indicated that the patients more promptly
      emerged from phtorotan anesthesia; however, they require preventive analgesia.

PMID- 16613042
TI  - [Diagnosis and treatment of ventilator-associated pneumonia in children].
AB  - The purpose of the investigation was to optimize the diagnosis and treatment of
      ventilator-associated pneumonia (VAP) in children. The prevalence, etiology, and
      onset of VAP in a pediatric intensive care unit, and the diagnostic value the
      clinical pulmonary infection score scale were studied. The prevalence of VAP was
      found to be 37.56 per 1,000 mechanical ventilation days, and the CPIS scale was
      not always useful in diagnosing VAP in children. The most common causative agents
      of VAP were Enterobacteriaceae spp, and its major pathogen is P. aeruginosa.
      Early adequate antibacterial therapy prevents and treats VAP, without causing any
      complications.

PMID- 16613043
TI  - [Treatment of neonatal respiratory distress syndrome with surfactant BL].
AB  - The paper presents the results of use of the Russian drug Surfactant BL as part
      of complex intensive care of respiratory distress syndrome (RDS) in the premature
      newborn. The drug was used in 45 children (a study group). A control group
      comprised 52 children with RDS who had undergone a course of therapy before the
      use of the drug at our clinic. Statistical analysis indicated the practical
      uniformity of the study and control groups. Particular emphasis was laid on the
      study of changes in the parameters of blood oxygenation and those of artificial
      ventilation (AV) regimens in both groups of children. The study demonstrated that
      in the Surfactant BL-treated patients, blood oxygenation (pO2, A-aDO2,
      respiratory coefficient) improved much more rapidly and, from the end of the
      first day of treatment to the termination of therapy in the intensive care unit
      of a maternity hospital, the mean values of these parameters remained
      statistically significantly better than those in the controls. In the study
      group, under AV, insufflated gas FiO2 could be reduced more rapidly and by a
      large quantity and some other AV parameters "attenuated". Analyzing the outcome
      of treatment of neonatal infants with RDS has indicated that Surfactant BL has a
      statistically significant advantage in the positive outcomes of treatment in a
      group of patients treated with this agent as part of complex intensive care.

PMID- 16613044
TI  - [Infusion therapy for burn shock in children].
AB  - The study deals with infusion therapies in children with thermal injury and with
      its impact of its qualitative composition at the local (tissue) and systemic
      levels. The investigations have indicated that the best qualities' in
      replenishing the volume of circulating blood and in eliminating hypovolemia are
      shown by hydroxyethylated starch (the study used voluvene) that offers advantages
      in the rate of correction of blood concentrations and in the maintenance of a
      volumic effects and that increases oxygen delivery, resulting in a rapider
      emergency from shock and improving the trophism of a burn wound.

PMID- 16613045
TI  - [Experience with a selenium-containing biological active supplement used in
      children with pneumonias in an intensive care unit].
AB  - The efficacy of the biologically active additive (BAA) "Spirulin-Sochi-Selen" was
      evaluated in 45 children aged 3 to 15 years who had acute pneumonia treated in
      the intensive care unit for infected patients of the Tushino children's city
      hospital, Moscow. The levels of selenium were determined by the Alfthan
      microfluorimetric technique (1984). The time course of clinical, laboratory,
      functional, and X-ray changes was determined. A control group comprised 20
      children taking no selenium-containing foods or biologically active additives.
      The findings suggest that the BAA "Spirulin-Sochi-Selen" is effective as part of
      therapy for acute pneumonia in children treated in an intensive care unit. There
      were no signs of selenium deficiency in any case despite the baseline reduction
      in the average serum levels in both groups.

PMID- 16613046
TI  - [Short bowel syndrome in children: etiology and basic approaches to treatment].
AB  - The paper considers the main causes and clinical manifestations of the short
      bowel syndrome in children, defines the clinical and physiological features of
      the disease in children. The world experience in managing patients with short
      bowel syndrome is summed up. Indications for total parenteral or parenteral-and
      enteral feeding in relation to the site of intestinal resection are analyzed.
      Artificial therapeutic feeding is shown to play the leading role in the complex
      of rehabilitation of children with short bowel syndrome.

PMID- 16613047
TI  - [Procedure for determining the initiation of tube feeding in children in an
      intensive care unit].
AB  - A procedure is proposed to determine the timing of tube feeding in children
      treated in an intensive care unit, which records the hypertonia of the pyloric
      sphincter and consists in the determination the time of gastric administration of
      distilled water before its evacuation into the duodenal lumen (water evacuation
      test) visualized in the real-time mode through abdominal ultrasonography. The
      proposed procedure was successfully applied to 42 children aged 3 months to 14
      years who had severe brain injury, appendicular peritonitis, polytrauma, and
      polysegmental pneumonias. This determining procedure makes it possible to exclude
      radiation exposure in patients treated in intensive care units and to improve the
      outcomes of treatment, by prescribing the artificial feeding, that is adequate to
      the patients' status, in the periods optimal for each specific clinical case.

PMID- 16613048
TI  - [Organization of anesthesiological care of children in outpatient surgical
      practice].

PMID- 16613049
TI  - [Organizational aspects of medical care delivery to children during emergency
      situations].

PMID- 16613050
TI  - [Transcutaneous dilation tracheostomy in children].
AB  - The paper presents the experience of transcutaneous dilatation tracheostomy (TDT)
      in 16 children. Up to date, childhood has been a contraindication for TDT. The
      experience gained at the Department of Resuscitation, Institute of Neurosurgery,
      in performing TDT in more than 300 adult patients has permitted this procedure to
      be also used in childhood. Based on the analysis of the outcome of 16 TDTs, the
      authors have posed indications for TDT, its performance modification, approaches
      to preventing perioperative complications, by taking into account the anatomic
      and physiological characteristics of childhood.

PMID- 16613051
TI  - [Evolution of the sepsis terminology in children over the past decade].

PMID- 16613052
TI  - [Hypermetabolism syndrome in critically ill children].
AB  - The paper focuses on the developmental mechanisms and triggers of
      hypermetabolism, by describing the specific features of pathophysiological
      reactions occurring in the child's body. It also shows the leading role of
      artificial therapeutic feeding included into the multimodality therapy of
      children under stresses in restoring plastic and energy demands and in preventing
      the development of multiple organ dysfunction.

PMID- 16613053
TI  - [The influence of space flights on water-electrolytes turnover and its
      regulation].
AB  - A study of water-electrolyte exchange, the condition of water milieu of the
      organism, and the volume- and electrolyte homeostasis regulation in space
      flights, and also in postflight period has shown the important role of the water
      salt homeostasis in adaptation of the human and animal organism to
      weightlessness. Obviously, downturn of food consumption, renal excretion and the
      intestine output seem to be caused by suppression of activity of mechanisms of
      ion deposition. The most intensive changes of the liquid milieu volumes occur in
      the first days of weightlessness or in its ground simulation. And, with prolonged
      duration, the changes of extracellular liquid volume and the volume of plasma do
      not extend. After termination of long space flights, activation of renin
      aldosterone systems occurs as well as a decrease in efficiency of antidiuretic
      hormone, misbalance of pressor/unpressor prostanoids. In the period of re
      adaptation after space flights, development of desensitization of kidneys to
      endogenous ADH occurs. This is the basis for researches directed to improvement
      of the existing scheme of correction of the hydrogenous status of the astronaut
      organism in the closing stage of flight.

PMID- 16613054
TI  - [Three types of miniature inhibitory potentiaes in the frog spinal cord
      motoneurons: the possibility of GABA and glycine co-release].
AB  - Miniature inhibitory postsynaptic potentials (mlPSPs) were recorded from
      motoneurons of the frog isolated spinal cord after blocking action potentials and
      ionotropic glutamate receptors (TTX 1 mcm: CNQX 25 mcm, D-AP5 50 mcm). Three
      types of mlPSPs were selected by their time characteristics) fast, slow and
      mlPSPs with two decay time constants. We classified 8.7% of mlPSPs as dual
      component, 64.5% as fast mlPSPs, and 26.8% as slow mlPSPs. The GABA(A)R blocker
      bicuculline (20 mcm) diminished the number of the slow and dual-component events
      while the number of mlPSP with a fast kinetics was increased. The GlyR antagonist
      strychnine (1 mcm) reduced the frequency of fast mlPSPs and increased this
      parameter of slow mlPSPs. These data suggest existence of three different mlPSP
      groups distinguished by their kinetics and sensitivity to receptor antagonists:
      fast events mediated by glycine, slow events mediated by GABA and dual-component
      mlPSPs corresponding to glycine and GABA co-release.

PMID- 16613055
TI  - [Mechanisms of blockade of glutamate receptors channels: the significance for
      structural and physiological investigations].
AB  - The mechanism of blocking effect of phenylcyclohexyl derivative, IEM-1925, on
      ionotropic glutamate receptors of the NMDA and AMPA types has been studied on the
      rat isolated brain neurons. The whole-cell configuration of patck clanp recording
      technique was used equilibrium conditions and -80 mV holding potential, the IEM
      1925 manifests nonselective action on open channels of both receptors. However,
      the prominent differences in the mechanism of the blocking effect were revealed.
      Although IEM-1925 can not enter the closed channels of both types, its molecule
      are able to leave closed channels of the AMPA but not the NMDA receptors.
      Hyperpolarization reduces removal of blocker from the open channels of the NMDA
      receptors. Contrary to that, hyperpolarization facilitates going out of the IEM
      1925 to cytozol from both open and closed channels. Evidently, the bloker can
      pass through the AMPA receptor channels into the cell, and the gating mechanism
      of these channels is located above the binding site for the blocker. The blocking
      action of the IEM-1925 on the NMDA and AMPA receptors was compared with its
      potency to weaken the tremor evoked by subcutaneous injection of arecoline to
      mice. The observed differences in the mechanisms of action help to explain the
      ambiguous effects of channel blocking drugs on experimental models of
      pathological processes.

PMID- 16613056
TI  - [Participation of the DNA-binding cytokine amphoterine in triggering the
      processes of tissue reparation].
AB  - Author's studies and literature references indicate that the DNA-binding
      cytokine: amphoterine, being a non-histone component of chromatin, acts in
      extracellular milieu as cytokine regulating gene expression in target cells. The
      amphoterine effects are mediated by its interaction with the cell surface
      receptors including those of the final glucosiding product (RAGE), which leads to
      activation of the ERK and p38 MAP-kinases as well as NF-kappaB. Amphoterine
      prompts inflammatory response by means of activating synthesis of interleukins-1,
      -6 and -8 as well as tumour necrosis factors (TNF-alpha) and activates tissue
      regeneration by means of involvement of the precursor cells into the damage foci
      and induction of the cells' differentiation. These properties of amphoterine
      suggest that appearance of this protein in extracellular space signals of a
      tissue damaging.

PMID- 16613057
TI  - [Developmental peculiarities of short-term nongenomic effect of aldosterone on
      intracellular sodium concentration in rat distal nephron].
AB  - Intracellular sodium concentration in CCD fragments micro-dissected from the
      kidneys of 10-day and adult rats using fluorescent dye Na+ Green, was studied.
      The steady state level of intracellular sodium was lower in fragments from
      amiloride kidney (24.50 +/- 1.3 and 35.3 +/- 4.9 mM, n = 8, respectively).
      Amiloride reduced this parameter but, in the epithelia cells from immature
      kidney, the effect of imaloride was less pronounced. Fast nongenomic action of
      aldosterone on intracellular sodium concentration was found in both groups.
      Aldosterone significantly raised the steady state sodium level in epithelial
      cells in conditions of low sodium concentration (14 mM) in outer medium in both
      type of CCD fragments: from 10-day pups and adult animals (4.0 +/- 1, 5.5 +/- 0.5
      and 5.1 +/- 0.2, 7.9 +/- 0.2 mM, n = 8). We suggest that, along with the well
      known mineral-corticoid effect, aldosterone takes part in regulation of cell
      volume in CCD rat kidney from the earliest stages of postnatal ontogenesis.

PMID- 16613058
TI  - [Physico-chemical determinants of physiOlogical evolution: from protocell to the
      human].
AB  - One of the key physiological problems of evolution is elucidation of the role of
      environmental inorganic factors in origin of life. A statement is substantiated
      that a highly significant event in evolution of life was the appearance of
      protocells with the K cytoplasm in K water reservoirs with their subsequent
      adaptation to the environment in which Na dominated. This step was accompanied by
      replacement of the cell envelope with the cell plasma membrane. Precursors of
      animals' elaborated mechanism of maintenance of the K-cytoplasm with Na
      counterkation in the environment. In plants, Na remains a trace element, in
      animals the Na and K contents are approximately equal, but they are present in
      different fluid phases. In animals presence of Na+ in the external medium, K+
      inside cells has become an initial pre-requisition for electrogenesis and
      appearance of asymmetrical cells. Electrogenesis of these cells has become a
      physiological pre-requisition for cell differentiation, the appearance of the
      nerve cell. Asymmetrical cell has provided development of absorption, digestion,
      excretion, respiration. Formation of the inner medium has become a prerequisite
      for establishment of homeostasis. Serum osmolality, sodium concentration, pH,
      Ca2+ are the most rigidly maintained constants in the blood serum of humans.

PMID- 16613059
TI  - [Analysis of auditory information in the brain of the cetacean].
AB  - The cetacean brain specifics involve an exceptional development of the auditory
      neural centres. The place of projection sensory areas including the auditory that
      in the cetacean brain cortex is essentially different from that in other mammals.
      The EP characteristics indicated presence of several functional divisions in the
      auditory cortex. Physiological studies of the cetacean auditory centres were
      mainly performed using the EP technique. Of several types of the EPs, the short
      latency auditory EP was most thoroughly studied. In cetacean, it is characterised
      by exceptionally high temporal resolution with the integration time about 0.3 ms
      which corresponds to the cut-off frequency 1700 Hz. This much exceeds the
      temporal resolution of the hearing in terranstrial mammals. The frequency
      selectivity of hearing in cetacean was measured using a number of variants of the
      masking technique. The hearing frequency selectivity acuity in cetacean exceeds
      that of most terraneous mammals (excepting the bats). This acute frequency
      selectivity provides the differentiation among the finest spectral patterns of
      auditory signals.

PMID- 16613060
TI  - [Mirror brain systems, concepts and language: the price for anthropogenesis].
AB  - The paper discusses the problem of cognitive evolution and the basis for the
      origin of language and mind, genetic history of Homo sapiens and whether the
      basic concepts are inborn or effected by experience, sensory or cognitive per se.
      The problem of localization of higher functions and Theory of Mind in norm and
      pathology is analyzed.

PMID- 16613061
TI  - [Creatine as a metabolic controller of skeletal muscles structure and function in
      strength exercises in humans. The cellular mechanisms].
AB  - The effects of creatine oral supplementation combined with a 10-week resistive
      training of morphometric, contractile and molecular characteristics of human vast
      lateral muscle fibers were studied. 2 groups consisting of 9 young healthy men
      each were involved in resistive training of knee extensors for 10 weeks.
      Volunteers of the first group received per os 20 g of creatine for the 1st week
      of training and 5 g for the rest of the experimental training period. We found a
      significant increase of slow and fast-twitch fiber size in both trained groups
      and a significant increase of Ca-sensitivity of skinned single fiber
      contractility in creatine-supplemented group. The serum creatine phosphokinase
      activity in blood samples taken 24 hours after exercise session increased in all
      stages of the experimental training in both groups. At the same time, the
      adaptive decrease of the after-exercise CK concentration was observed in the
      placebo but not in the creatine-supplemented group. The altered integrity of the
      subsarcolemmal dystrophin layer was revealed in both groups after training.

PMID- 16613062
TI  - [Creatine as a metabolic controller of skeletal muscles structure and function in
      strength exercises in humans].
AB  - The aim of study was to investigate the effect of oral creatine supplementation
      upon muscle performance and aerobic capacity of the organism. Knee extensor
      muscles of two groups with 9 subjects in each were subjected to strength training
      with and without creatine supplementation (Cre and Pla) for 10 weeks, three times
      a week with an effort of up to 85% of maximal voluntary contraction (MVC). The
      Cre group received 5 g of creatine monohydrate a day. After 10 weeks strength
      training, an increase of MVC by 29 and 40% in training (isotonic) regimen was
      recorded for the Pla and Cre groups respectively. The muscle isokinetic torque
      increments of 10-11% were obtained in the Pla group at angular velocities
      corresponding to training velocities, and in the Cre group increments of 11-17%
      were recorded at all angular velocities tested. No changes were found in the
      fatigue test by the Pla group, whereas Cre group showed a tendency for an
      increase. The aerobic and anaerobic capacities of the organism did not decrease
      in both groups. Thus the creatine supplementation during strength training
      potentates an increase of force-velocity characteristics of trained muscle group
      without impeding aerobic capacity of the organism.

PMID- 16613063
TI  - [The stress effect in the prenatal period on sexual excitation and sexual
      orientation of the mice males].
AB  - Estrus female behind holed transparent partition produced sexual motivation and
      sexual arousal in males. It was manifested in behavioral changes (an increase in
      time spent near the partition) and the testosterone level augmentation in blood.
      Female mice were exposed to stress (1 h/day restraint) in the last week of
      gestation. Prenatal stress was shown to decrease the blood corticosterone level
      as well as to diminish sexual motivation and sexual arousal in adult male mice.
      Estrus female exposure produced a lesser behavioral response and a lesser
      testosterone level augmentation. No changes in weight of testicles, seminal
      vesicles or adrenal glands were found, but preputial gland weight increased. In
      prenatally stressed males, a female preference decrease and a male preference
      increase were revealed in the partner preference test. These data suggest that
      prenatal stress decreases sexual motivation in males and leads to clear
      predisposition to homosexuality, although it does not produce complete inversion
      of sexual orientation.

PMID- 16613064
TI  - [Ivan Petrovich Pavlov and William Gant--encounter of generations, unknown
      photos].

PMID- 16613065
TI  - [Preventive medicine in times of a rapid epidemiologic transition in Korea].
AB  - Ever since the foundation of the Korean Society for Preventive Medicine in 1947,
      members of the Society had made remarkable contributions to the public health
      development and national health promotion. They had played key roles in
      establishing national health system, improving environmental hygiene, controlling
      infectious and chronic diseases, promoting family planning, improving industrial
      and environmental health, and developing health service management. However, the
      Society had less actively responded to the changes in health service needs of the
      population that were caused by a rapid epidemiologic transition in last a few
      decades. Early detection and treatment of chronic diseases including cancer and
      cardiovascular diseases and risk reduction by the life style modification are
      major approaches to the contemporary national health problems and they are the
      core contents of preventive medicine. The author proposed to develop the clinical
      preventive medicine specialist who will have additional training in clinical
      medicine for health screening and life style modification to the current
      preventive medicine training program and thus will be able to provide
      comprehensive preventive medical services. Another area that the Society may take
      the initiative is training preventive medicine specialist in the disaster,
      including bioterrorism, preparedness and management. The Society should be more
      active in proposing health policy and health service program and also participate
      collectively in a large scale health research project of the government. These
      approaches may not only contribute more effectively to the national health
      promotion but also improve the identity of the Society.

PMID- 16613066
TI  - [Future of preventive medicine education in Korea: hopes and challenges].
AB  - Throughout the century, based on the precedent set by Flexner in the United
      States, almost every subsequent report on the reform of medical education has
      pointed out the need for more prevention-oriented teaching in the curriculum.
      This has been particularly so in countries like Korea where the basic public
      health services have been so important for the improvement of health of the
      people. And, in fact, preventive medicine and public health have contributed a
      great deal to the prevention of communicable diseases and prolongation of life
      expectancy. Recently, however, along with the educational reform that emphasizing
      the interdisciplinary teaching, integration of basic science and clinical
      education, and centralization of responsibility for the medical education
      curriculum, concerns are being voiced by preventive medicine educators. These
      concerns are primarily centered around the fear that the implementation of
      interdisciplinary, centrally administered courses would result in a weakening of
      content and teaching expertise as well as a loss of departmental power and
      control. This paper foresees that preventive medicine and public health will be
      more important in Korea in the future and proposes that preventive medicine
      educators will have to step forward and turn the challenges of curricula
      restructuring into opportunities to expand the role of preventive medicine in the
      curricula of their institutions.

PMID- 16613067
TI  - [Does a higher coronary artery bypass graft surgery volume always have a low in
      hospital mortality rate in Korea?].
AB  - OBJECTIVES: To propose a risk-adjustment model with using insurance claims data
      and to analyze whether or not the outcomes of non-emergent and isolated coronary
      artery bypass graft surgery (CABG) differed between the low- and high-volume
      hospitals for the patients who are at different levels of surgical risk. METHODS:
      This is a cross-sectional study that used the 2002 data of the national health
      insurance claims. The study data set included the patient level data as well as
      all the ICD-10 diagnosis and procedure codes that were recorded in the claims.
      The patient's biological, admission and comorbidity information were used in the
      risk-adjustment model. The risk factors were adjusted with the logistic
      regression model. The subjects were classified into five groups based on the
      predicted surgical risk: minimal (<0.5%), low (0.5% to 2%), moderate (2% to 5%),
      high (5% to 20%), and severe (=20%). The differences between the low- and high
      volume hospitals were assessed in each of the five risk groups. RESULTS: The
      final risk-adjustment model consisted of ten risk factors and these factors were
      found to have statistically significant effects on patient mortality. The C
      statistic (0.83) and Hosmer-Lemeshow test (x2=6.92, p=0.55) showed that the
      model's performance was good. A total of 30 low-volume hospitals (971 patients)
      and 4 high-volume hospitals (1,087 patients) were identified. Significant
      differences for the in-hospital mortality were found between the low- and high
      volume hospitals for the high (21.6% vs. 7.2%, p=0.00) and severe (44.4% vs.
      11.8%, p=0.00) risk patient groups. CONCLUSIONS: Good model performance showed
      that insurance claims data can be used for comparing hospital mortality after
      adjusting for the patients' risk. Negative correlation was existed between
      surgery volume and in-hospital mortality. However, only patients in high and
      severe risk groups had such a relationship.

PMID- 16613068
TI  - [Socioeconomic costs of alcohol drinking in Korea].
AB  - OBJECTIVES: We wanted to estimate the annual socioeconomic costs of alcohol
      drinking in Korea. METHODS: The costs were classified as direct costs, indirect
      costs and the other costs. The direct costs consisted of direct medical costs,
      indirect medical costs and subsidiary medical costs. Particularly, the medical
      costs and population attributable fraction for disease were considered to reflect
      the calculation of the direct medical costs. The indirect costs were computed by
      the extent to which the loss of productivity and loss of the workforce might have
      occurred due to changes in mortality and morbidity according to alcohol drinking.
      The other costs consisted of property loss, administration costs and costs of
      alcoholic beverage. RESULTS: The annual costs, which seemed to be attributable to
      alcohol drinking, were estimated to be 149,352 hundred million won (2.86% of
      GDP). In case of the latter, the amount includes 9,091 hundred million won for
      direct costs (6.09%), 62,845 hundred million won for the reduction and loss of
      productivity (42.08%), 44,691 hundred million won for loss of the workforce
      (29.92%), and the other costs (21.91%). CONCLUSIONS: Our study confirms that
      compared with the cases of Japan (1.9% of GNP) and the other advanced countries
      (1.00-1.42% of GDP), alcohol drinking incurs substantial socioeconomic costs to
      the Korean society. Therefore, this study provides strong support for government
      interventions to control alcohol drinking in Korea.

PMID- 16613069
TI  - [A multilevel study on the relationship between the residential distribution of
      high class (power elites) and smoking in Seoul].
AB  - OBJECTIVES: We examined whether the neighborhood socioeconomic position predicts
      the smoking rates after adjusting for individual socioeconomic position
      indicators. METHODS: Data were obtained from the 2001 Seoul Health Indicators
      Survey. The neighborhood socioeconomic position was the residential distribution
      of the high class (power elites), as measured by the location quotients (LQ) for
      each administrative dong (district). A high LO denotes a high neighborhood
      socioeconomic status. The individual socioeconomic position included education,
      occupation and income. Age-adjusted smoking rates according to the LQ level were
      computed with the direct method. The total number of subjects in this study
      (26,022 men and 28,007 women) was the reference. A multilevel logistic regression
      analysis was conducted with the individuals at the first level and the
      neighborhoods at the second level to estimate the odds ratios of smoking with 95%
      confidence intervals. RESULTS: For men, the age-adjusted smoking rates increased
      with a decrease in the LQ. For women, the relationship between the age-adjusted
      smoking rate and the LQ was not clear. The odds of smoking for both genders were
      greater among those subjects with lower incomes and lower education. The manual
      occupational class had greater odds of smoking than the non-manual class for the
      males, while the odds ratio of smoking among females with a manual occupation
      tended to be lower than those females with a non-manual occupation. For the
      males, the LQ levels independently predicted smoking after adjustment for
      individual income. However, this relation between the LQ and smoking in males was
      explained by full adjustment for the individual socioeconomic position indicators
      (education, occupation and income). CONCLUSIONS: A low level of neighborhood
      socioeconomic position was associated with higher smoking rates among the men
      residing in Seoul. This association between the neighborhood socioeconomic
      position and smoking in men was explained by the individual socioeconomic
      position. Anti-smoking efforts to reduce geographical inequality in smoking
      should be directed at reducing the smoking rates between the individuals with
      different socioeconomic backgrounds in the metropolitan city of Seoul, South
      Korea.

PMID- 16613070
TI  - [Estimating the burden of psychiatric disorder in Korea].
AB  - OBJECTIVES: This study estimated the burden of disease especially caused by
      psychiatric disorders in Korea by using DALY, a composite indicator that was
      recently developed by the Global Burden of Disease study group. METHODS: First,
      11 of the major psychiatric disorders in Korea were selected based on the ICD-10.
      Second, the burden of disease due to premature death was estimated by using YLLs
      (years of life lost due to premature death). Third, for the calculation of the
      YLD (years lived with disability), the following parameters were estimated in the
      formula: the incidence rate, the prevalence rate and the disability weight of
      each psychiatric disorder. Last, we estimated the DALY of the psychiatric
      disorders by adding the YLLs and YLDs. RESULTS: The burden of psychiatric
      disorder per 100,000 people was attributed mainly to unipolar major depression
      (1,278 person-years), schizophrenia (638 person-years) and alcohol use disorder
      (287 person-years). For males, schizophrenia (596 person-years) and alcohol use
      disorder (491 person-years) caused the highest burden. For females, unipolar
      major depression (1,749 person-years) and schizophrenia (680 person-years) cause
      the highest burden. As analyzed by gender and age group, alcohol use disorder
      causes a higher burden than schizophrenia in men aged 40 years and older. For
      females, unipolar major depression causes the highest burden in all age groups.
      CONCLUSIONS: We found that each of the psychiatric disorders that cause the
      highest burden is different according to gender and age group. This study's
      results can provide a rational basis to plan a national health policy regarding
      the burden of disease caused by psychiatric disorders.

PMID- 16613071
TI  - [The relationship between regional material deprivation and the standardized
      mortality ratio of the community residents aged 15-64 in Korea].
AB  - OBJECTIVES: This study was performed to investigate the relationship between
      regional material deprivation and the standardized mortality ratios(SMRs) of
      community residents aged 15-64 in Korea. METHODS: SMRs were investigated using
      the registered death data from 1995 to 2000 that was obtained from the Korean
      National Statistics Office with the denominators being drawn from the 1995 to
      2000 census. Material deprivation was measured using the Townsend score that was
      calculated from the 1995 to 2000 census. The relationship between the regional
      material deprivation and the SMRs of the community residents aged 15-64 was
      investigated by using ANOVA, Spearman's rank correlation analysis and Pearson's
      correlation analysis. The trends in mortality inequality were investigated using
      the concentration index. RESULTS: On the ANOVA, the SMRs of the men and women
      residents in the least deprived areas were the smallest and those in the most
      deprived areas were the largest. Spearman's rank correlation analysis, Pearson's
      correlation analysis and the concentration index revealed that significant
      positive relationships exist between the regional material deprivation and the
      SMRs of the community residents aged 15-64. CONCLUSIONS: This study suggests that
      there are mortality inequalities among the communities in Korea and part of this
      difference is due to the material deprivation of the community. Strategies aimed
      at reducing mortality inequalities among the communities will be needed to
      address economic inequalities. Further studies are needed to explore the
      mechanisms of how the regional deprivation influences on health and how the other
      factors of the community influence on the health of the community residents.

PMID- 16613072
TI  - [Human multi-route exposure assessment of lead and cadmium for Korean
      volunteers].
AB  - OBJECTIVES: We wanted to evaluate the main route of exposure to lead and cadmium
      for the general population in Korea by using multi-route and multi-media exposure
      assessment METHODS: Samples of air at the homes, samples of the food and water
      and peripheral blood samples were collected from thirty volunteers living in
      Seoul (the metropolitan area), Yong-in (the suburban area) and Ansan (the
      industrial area) in 2001. Graphite furnace atomic absorption spectrometric
      methods were used for the determination of the Pb and Cd levels in the air, food,
      water and blood samples. RESULTS: The average intake of lead through the air,
      drinking water and food were 5.06 microg/day (26.3%), 0.002 microg /day (0.1%),
      and 16.4 microg/day (73.6%), respectively. The average intake of cadmium through
      the air, drinking water and food were 0.082 microg/day (0.9%), 0.001 microg/day
      (0.007%), and 12.61 microg/day (99.0%), respectively. The blood lead level was
      statistically higher in the male subjects than in the female subjects (3.39 and
      2.22 microg/dl, respectively), and only gender was a significant variable on the
      multiple regression analysis for blood lead. CONCLUSIONS: This study showed that
      the intake of lead and cadmium through food was the major route of exposure. A
      policy to reduce the pollutants according to the exposure routes should be
      established. However, more studies will be needed to support these data for the
      general population.

PMID- 16613073
TI  - [Health behavior factors affecting waist circumference as an indicator of
      abdominal obesity].
AB  - OBJECTIVES: This study was performed to identify the socioeconomic factors, the
      psychosocial factors and the heath behavior factors that have an influence on
      abdominal obesity, as measured by using the waist circumference. METHODS: Data
      was obtained from individuals aged above 20 years who had their waist
      circumference measured on the Korean National Health and Nutrition Examination
      Survey 2001, which was a cross-sectional health survey. RESULTS: Regression
      analysis of the factors that affect abdominal obesity showed that the education
      level, income, smoking, duration of smoking, drinking consumption, frequency of
      exercises and sleeping were the associated factors for abdominal obesity. For
      men, the duration of smoking, education level, income and drinking consumption
      were the associated factors for abdominal obesity. For woman, the education
      level, income, duration of smoking, drinking consumption and frequency of
      exercise were the associated factors for abdominal obesity. CONCLUSIONS:
      Abdominal obesity is a risk factor for morbidity and mortality, and it is
      associated with chronic diseases, including cardiovascular disease and diabetes.
      Based on the findings, it is essential to modify heath behaviors for preventing
      abdominal obesity, which is a condition associated with the incidence of chronic
      disease.

PMID- 16613074
TI  - [Related factors for the initiation of smoking in high school students based on
      the transtheoretical model].
AB  - OBJECTIVE: This study was conducted to investigate the relationship between the
      intention of smoking and its related factors in high school students. METHODS:
      Our study subjects were 1,203 high school students who resided in one city and in
      one county region. We conducted a self-administered questionnaire survey from
      June 7 to June 19, 2004. Both the decisional balance and temptation inventory
      showed high reliability estimates. We provided good fit for the 12-item
      decisional balance inventory and the 10-item temptation inventory by using a
      confirmatory factor analysis. We also used multiple logistic regression analysis
      to identify the major contributing factors for the intention to start smoking.
      RESULTS: On the univariate analysis, the subjects who were female, the 2nd and
      3rd grade students,the students in vocational high school, the ex-drinkers or
      current drinkers, and ex-smokers were found to be significantly more distributed
      in the groups with intention to start smoking. Except for the concept of the
      cons, the group with intention to start smoking showed significantly higher
      standardized T scores for the 7 concepts of decisional balance and temptations.
      On the multiple logistic regression analysis, the females, the 2nd and 3rd grade
      students, the students in vocational high school, the experience of cigarette
      smoking and low T score of the cons were significantly related to the intention
      to start smoking. CONCLUSIONS: The intention to start smoking in high school
      students was affected by various factors such as gender, the school grade and the
      experience of smoking. Therefore, further research should be conducted for
      providing the essential data for developing a brief instrument for selecting the
      groups with intention of starting smoking among adolescents.

PMID- 16613075
TI  - [Factors affecting breastfeeding rate and duration].
AB  - OBJECTIVES: The purpose of this study is to examine the factors affecting the
      rate and duration of breastfeeding. METHODS: We analyzed the data from the year
      2000 Korea National Fertility Survey that was collected through direct
      interviews. In particular, the mothers who delivered their last child and the
      child was under 1 year of age from January 1998 to June 2000 (N=1,066) were
      analyzed via a logistic model to assess the factors affecting the breastfeeding
      rate. Among the study subjects, those who had initiated breastfeeding (N=740)
      were analyzed through Cox's proportional hazard model to evaluate the factors
      affecting the duration of breastfeeding. RESULTS: The multivariate logistic model
      showed that the delivery type and the baby's birth-weight have a statistically
      significant influence on the breastfeeding rate. Women who delivered their babies
      through Cesarean section were less likely than others to breastfeed. In contrast,
      the women whose babies weighed 2.5 Kg or more were more likely than others to
      breastfeed. The results obtained from the survival analysis are as follows : the
      higher the mother's education level, the shorter is the breastfeeding duration.
      The mother's work status played a significant role in the early termination of
      breastfeeding. Women aged 35 or older showed a longer breastfeeding duration than
      the younger age groups, whereas the maternal age was not a significant factor in
      affecting whether or not a mother would breastfeed. CONCLUSIONS: Reducing the
      cases of operative delivery (Cesarean section) and low weight births,
      enlightening young and highly educated women on breastfeeding and improving the
      environment for breastfeeding on the job are important strategies to encourage
      women to breastfeed.

PMID- 16613077
TI  - [The reasons for a nursing prescription].

PMID- 16613076
TI  - [Relationship between the exposure to ozone in Seoul and the childhood asthma
      related hospital admissions according to the socioeconomic status].
AB  - BACKGROUND: A number of studies have reported associations between the ambient
      air pollution concentrations and various health outcomes. Especially, ozone is
      well known for primary risk factor of asthma attacks. The results of a recent
      study indicate that the size of the effect on health outcomes due to air
      pollution varied according to several conditions, including age, gender, race and
      the socioeconomic status. Therefore, this study was conducted to examine the
      associations of ozone with the childhood asthma hospitalizations as stratified by
      the socioeconomic status (SES) at the community level in Seoul, Korea, 2002.
      METHODS: SES at aggregated levels was measured on the basis of average regional
      health-insurance rate per citizen in the area. We applied the generalized
      additive model to analyze the effect of ozone on asthma after controlling for the
      potential confounding variables that were capable of influencing the results.
      RESULTS: Our analysis showed that the number of children who were hospitalized
      for asthma increased as the SES of the residence area decreased. The estimated
      relative risks of hospitalization for asthma, as stratified by the SES of the
      community level, were 1.12 (95% confidence interval 1.00-1.25) in districts with
      the highest SES levels, 1.24 (95% CI=1.08-1.43) within the moderate SES levels,
      and 1.32 (95% CI=1.11-1.58) in the districts with the lowest SES levels.
      CONCLUSIONS: Our analysis showed that exposure to air pollution did not equally
      affect the health status of individuals. This suggests that not only the
      biological-sensitivity markers, but also the SES of the subjects should be
      considered as potentially confounding factors.

PMID- 16613078
TI  - [Diabetic foot].
AB  - In many instances, a diabetic foot poses a serious health problem due to its
      multiple complications. To prevent this from happening, it is necessary to know
      the characteristics of a diabetic foot, the complications associated with it, and
      to evaluate the effectiveness of health education as a preventive measure. This
      article takes all these points as its objectives.

PMID- 16613079
TI  - [Manifesto for reading. "Bad times are those in which we have to fight for what
      is obvious"].

PMID- 16613080
TI  - [Nursing professionals' reading habits; a study in a hospital in Granada].
AB  - In all the hospital library standards, as well as in the existing Accreditation
      Norms for hospitals, a section is included which cites the distinct professionals
      who work at the institution which the library services must attend to provide for
      their scientific information needs. Among the sanitary collectives, nursing
      professionals are explicitly listed. Nonetheless, since the creation of hospital
      library services in Spain, many librarians have noticed that the nursing
      professionals, which compose the most numerous group in a hospital, have a very
      low library visitation rate in relationship to other collectives such as doctors
      in particular. Desiring to have objective data regarding library use, and not
      merely perceptions, the authors planned out a study in a large, 1.200 bed,
      hospital where more than 1.000 professionals comprise the nursing staff. The
      authors wanted to verify the nursing staff's needs for scientific information,
      their habits regarding their scientific information needs, and the possible
      difficulties which they encounter trying to acquire this type of information;
      furthermore, the authors wanted to know the nursing professionals' attitude
      towards this issue.

PMID- 16613081
TI  - [What we should know and how we should act when avian flu strikes].
AB  - The author presents an updated review on the flu and the ever more commented bird
      flu. The most highlighted aspects of this article deal with what composes flu and
      how one should act given the current circumstances.

PMID- 16613082
TI  - [The ethics of treatment: a proposal having a future for nurses and health
      companies].
AB  - This article is the fruit of various circumstances. In the first place, it is the
      result of a long reflection shared by its authors; it is also the proof of the
      primary interests the authors hold specific time; and lastly, it is the
      reflection of our opinion regarding how nurses should with their compromise a
      future treating patients.

PMID- 16613083
TI  - [The placenta, from a residue to a treasure].
AB  - Midwifes are the ones in charge of the procedure to obtain a blood donation from
      the umbilical cord, a procedure which consists of informing mothers what the
      advantages and inconveniences of such a donation are, filling out the file for
      the blood bank, extracting the blood donation, and completing the patient's
      records for the pediatrician. In Spain, the Spanish Register of Bone Marrow
      Donors (REDMO in Spanish acronym) is the organization in charge of internal
      coordination and in conjunction with other countries, the bone marrow and
      umbilical cord blood donations. Every pregnant woman in good health who does not
      meet the criteria for being excluded as a donor by the umbilical cord blood banks
      is considered to be a possible umbilical cord blood donor. Once an umbilical cord
      blood donation is extracted, the donation is stored, identified, processed and
      revised so that it can be sent to the blood bank designated for the hospital and,
      once there, when the opportune moment arrives, to the place where there is a
      compatible receiver At the present time, the number of donations of umbilical
      cord blood is increasing; but on the list of reasons to not donate there appears,
      to a high degree, the lack of knowledge about this type of donation among
      pregnant women. Therefore, health professionals role to inform pregnant women
      about umbilical cord blood donations is important.

PMID- 16613084
TI  - [Sleeping difficulties among the elderly].
AB  - Sleeping difficulties affect individuals at all ages, but the number of those
      affected increases in direct proportion to age. Frequently the elderly manifest
      their difficulties in achieving a satisfactory degree of sleep. This
      circumstance, which has a negative effect on their physical and psychological
      well-being, is a common reason to consult a doctor. However treatment with
      pharmaceuticals should not be considered a definitive solution. Health Education
      workshops make it possible to deal with sleep related difficulties in an
      integrated manner with a group of patients. These workshops enable health
      professionals to work with the elderly to analyze positive and negative factors
      which condition sleep, to know the changes which age produces in sleep patterns,
      to facilitate adapting to the aforementioned changes, to reeducate inadequate
      habits and to promote healthy life styles which make an improvement possible.
      Furthermore, in these sleep workshops, participants receive training in
      techniques to control stimuli and induce relaxation, developing skills which the
      elderly can daily employ.

PMID- 16613085
TI  - [Psychological repercussion of the scars in the burned patient].
AB  - The scars produced by burns have serious consequences for the patient. The
      repercussions go further than the discomfort, pain and physical restrictions,
      going as far as causing significant psychological consequences which can restrict
      the personal and social relationships of those affected. From the accounts told
      by two burn victims, and the technical analysis carried out by psychologists and
      psychiatrists specialised in this field, we gain a better understanding of the
      situation of these patients, on the basis of which we propose a series of nursing
      interventions designed to improve the care given in the area of wound healing.

PMID- 16613086
TI  - [Numbers are also words].
AB  - The author, leaving aside his development as a statistician, opens up to other
      proposals, reviewing some studies about qualitative research methodology as
      related to health sciences. He concludes that qualitative research complements
      quantitative research and that a subjective element exists in both: numbers are
      also words because behind numbers there is a reflexive process and a human
      interpretation.

PMID- 16613087
TI  - [Pain in the right iliac region in therapeutic practice].

PMID- 16613088
TI  - [Current ideas about gastrointestinal diseases associated with Helicobacter
      pylori].

PMID- 16613089
TI  - [Antibodies to Helicobacter pylori in gastric diseases].
AB  - AIM: To study the count of antibodies to Helicobacter pylori (ABHP), their role
      in diagnosis and prognosis in gastric diseases (GD). MATERIAL AND METHODS: Enzyme
      immunoassay (kits from EcoLab and Vektor-Best, Russia) was used to measure serum
      levels of ABHP (IgG, IgA, IgM+IgG+IgA) in 46 GD patients. RESULTS: It is shown
      that GD are characterized by a regular rise of serum ABHP which are serological
      markers of Helicobacter pylori infection. Percentage and absolute value of IgG-HP
      were the highest (78%, mean titer 1:604 vs control 1:110) as well as
      (IgM+IgG+IgA) antibodies to CagA-HP (approximately 82%, mean titer 1:160 vs.
      control 1:10); the level of IgA-HP was elevated by 39%, mean titer 1:442, control
      1:120. Elevated levels of IgG-HP reflect intensity of inflammatory processes, IgA
      HP--atrophic processes, IgM+IgG+IgA)-CagA-HP--proliferative processes in GD.
      CONCLUSION: High concentrations of ABHP are a diagnostic criterion of HP
      infection, reflect intensity of infectious, inflammatory, atrophic and
      proliferative processes in GD. Long-term persistence of elevated ABHP
      concentrations is one of the indications for application of antichelicobacter
      therapy in GD associated with HP while ABHP fall is an additional criterion of
      efficacy of the treatment.

PMID- 16613090
TI  - [Prevalence of polyresistance to antibiotics among Helicobacter pylori strains
      isolated from patients with gastroduodenal zone diseases].
AB  - To study prevalence of polyresistance (PR) among the strains of Helicobacter
      pylori isolated from patients with chronic gastritis, gastroduodenal ulcer and
      gastric cancer in Georgia. Material and methods. Biopsies of gastric mucosa and
      resection material were studied in 206patients with gastroduodenal zone diseases
      for identification of H. pylori (HP) and PR strains of HP. Results. The number of
      antibiotics involved in development of polyresistant strains varies from 3 to 8.
      The greatest number of strains (28.57 +/- 1.06%) develop PR to 5 antibiotics, the
      least--to 8 antibiotics. CONCLUSION: PR prevalence among HP strains is 35.25 +/-
      4.05%. PR is most frequently seen to metronidasol and oxacilline, least
      frequently--to amoxicilline and clarithromycin.

PMID- 16613091
TI  - [Effects of probiotic bifiform on efficacy of Helicobacter pylori infection
      treatment].
AB  - AIM: To study effects of the probiotic bifiform on efficacy of Helicobacter
      pylori (HP) eradication in patients with chronic gastritis and ulcer disease.
      MATERIAL AND METHODS: A total of 98 patients with verified HP infection were
      divided into two groups. The study group received a week three-component anti-HP
      therapy+a probiotic. The control group received the same treatment without the
      probiotic. All the patients were tested for HP before the treatment and one month
      after the end of the treatment. Cell composition of duodenal mucosa (DM), tissue
      proinflammatory cytokines, secretory immunoglobulin A (sIgA) in coprofiltrates,
      serum IgA, IgM, IgG, phagocytic parameters and copromicrobiology were studied.
      RESULTS: HP eradication rate in the study group was higher than in the control
      group (89.1 vs 63.5, respectively, p < 0.05). After the treatment, patients of
      the study group had lower rates of side effects, impaired intestinal biocenosis,
      tissue cytokines levels but higher concentration of plasmatic cells in CO and
      cIgA in coprofiltrates. CONCLUSION: The addition of probiotic bifiform to the
      standard three-component antihelicobacter scheme of the treatment raises its
      efficacy and is promising treatment of HP. Mechanisms of a potentiating action of
      the probiotic are related to enhancement of antibacterial activity of local
      immune reactions.

PMID- 16613092
TI  - [Time course changes in morphological and functional characteristics of gastric
      mucosa after eradication of Helicobacter pylori in duodenal ulcers].
AB  - AIM: To study trends in morphological changes of gastric mucosa (GM) and its
      functional characteristics (serum gastrin-17, pepsinogens I and II) in
      eradication of Helicobacter pylori (HP) in patients with duodenal ulcer (DU).
      MATERIAL AND METHODS: HP infection was detected with a rapid urease test,
      morphological study of gastrobiopsies and polymerase chain reaction in 59
      patients with DU. The results of HP eradication were assessed two months after
      the treatment. Morphological study of gastrobiopsies, assays for gastrin-17,
      pepsinogens I and II in blood serum were made before the treatment and one year
      after HP eradication. RESULTS: By the results of eradication two groups were
      formed: with effective eradication and uneffective eradication of H. pylori.
      Examination of GM one year after successful H. pylori eradication in DU patients
      GM inflammation relieved: reduction in polymorphonuclear (by 42.6%), mononuclear
      (by 29.3%) infiltration and number of lymphocytic follicules (16.8-fold). GM
      atrophy decreased by 47.8%. In patients with uneffective eradication the above
      positive changes were not registered. After H. pylori eradication, serum gastrin
      17 lowered by 46. 7%, pepsinogen I--by 30.5%, pepsinogen II--by 36.9%. In
      uneffective eradication this decrease did not occur. CONCLUSION: H. pylori
      eradication leads to positive changes in morphological and functional indices
      reflecting GM condition.

PMID- 16613093
TI  - [Quantitative-qualitative assessment of duodenogastric reflux at 24-h pH-metry].
AB  - AIM: To study characteristics (other than duration) of duodenogastric reflux
      (DGR), correlations of secretory function and DGR characteristics with
      gastroduodenal disorders (ulcer, chronic hyperacid gastritis). MATERIAL AND
      METHODS: A total of 110 patients were examined with 24-h pH-metry: 68 patients
      with duodenal ulcer (DU), 15 patients with gastric ulcer (GU), 27 patients with
      chronic hyperacid gastritis (CHG). Mean levels of pH and duration of hyperacidity
      in the body and an antral part of the stomach, duration of DGR, pH in the body
      and antral part of the stomach depending on DGR severity were studied. RESULTS:
      DGR was registered almost in all the patients with DU, GU and CHG. Groups of the
      patients differed by duration and height" of the DGR. CONCLUSION: Patients with
      DU are characterized by low refluxes which do not reach gastric body.

PMID- 16613095
TI  - [Quality of life in patients with duodenal ulcer].
AB  - AIM: To examine influence of duodenal ulcer (DU) on quality of life (QL) and
      changes in QL after different DU treatments. MATERIAL AND METHODS: QL in DU was
      assessed with Russian version of SF-36 questionnaire in 66 DUpatients with
      Helicobacter pylori (HP) aged 16-80 years (mean age 44.6 +/- 17.3 years).
      RESULTS: DU healing was achieved after 2 weeks of therapy with ranitidine (300
      mg/day), amoxicilline (2000 mg/day), metronidasole (1000 mg/day), and famotidin
      (40 mg/day), amoxicilline (2000 mg/day, clarithromycin (1000 mg/day) in 69.2 and
      94.9% cases (p = 0.04), after 4 weeks--88.2 and 96.8%, rrespectively (p = 0.52).
      Hospital stay was 16.1 +/- 2.1 and 22.2 +/- 3.4 (p < 0.05), respectively.
      Exacerbation of DU leads to deterioration of QL according to all the SF-36
      scales. Four weeks of therapy produced a statistically significant (p < 0.05)
      improvement of QL by all the scales. In failure of HP eradication QL worsened.
      CONCLUSION: QL is low in exacerbation of DU associated with HP. Antihelicobacter
      therapy improves QL of DUpatients. QL investigations help to select most
      effective therapy.

PMID- 16613094
TI  - [Complex evaluation of the action of inhibitors of hydrochloric acid secretion on
      gastric function in ulcer disease].
AB  - AIM: To characterize actions of inhibitors of hydrochloric acid secretion on
      gastric function and to formulate indications to using different antisecretory
      drugs in ulcer disease (UD). MATERIAL AND METHODS: Of 120 examinees with duodenal
      ulcer (DU), 40 received gastrocepin, 40--famotidin, 40--omeprasol. Follow-up
      study was made of motor, acid-, pepsin- and mucus-forming functions of the
      stomach. RESULTS: By reducing production of acid and pepsin, gastrocepin is
      inferior to famotidin and omeprasol. Gastrocepin is more effective than famotidin
      and omeprasol in motor-evacuatory dysfunction. Gastrocepin improves defensive
      properties of gastric mucus better. CONCLUSION: The results expand indications
      for a differential administration of antisecretory drugs in UD.

PMID- 16613096
TI  - [The course of gastroesophageal reflux disease in elderly patients with
      concomitant ischemic heart disease].
AB  - AIM: To study basic functional and pathogenetic features of the course of
      gastroesophageal reflux disease (GERD) in elderly patients with concomitant
      coronary heart disease (CHD). MATERIAL AND METHODS: Esophagogastroduodenoscopy,
      24-h pH-metry, simultaneous 24-h pH- and ECG-monitoring, omeprasol test were made
      in 126 patients: 74 GERD patients with CHD and 52 patients with GERD alone.
      RESULTS: Mean number of refluxes for 24 hours in isolated GERD was maximal at
      stages IIa and IIb (74%). In CHD patients (77%) there was a trend to a rise in
      this number. Only patients with associated CHD demonstrated a clinically
      significant depression of ST segment related to reflux, a significantly more
      frequent occurrence of supraventricular and ventricular extrasystoles.
      CONCLUSION: The acid component of gastric content pushed into the esophagus is
      not a leading factor of esophageal mucosa lesion in GERD patients with CHD.
      Pathological gastroesophageal refluxes may trigger mechanisms provoking new
      attacks of angina pectoris.

PMID- 16613097
TI  - [Celiac disease as a cause of iron deficiency anemia].
AB  - AIM: To examine incidence of celiac disease in patients with iron deficiency
      anemia (IDA) of unclear origin. MATERIAL AND METHODS: A total of 331 IDA patients
      were examined for celiac disease (CD). The diagnosis was made on the basis of
      histological findings upon examination of the biopsy of small intestinal mucosa,
      detection of antibodies to alpha-gliadine (AGA) and tissue transglutaminase
      (TTG). RESULTS: The cause of anemia was revealed in 270 (81.5%) of 331 patients.
      The rest 61 patients (18.4%) had anemia of unknown cause. A rise of AGA was
      detected in 33 (54.0%) of 61 patients, TTG--in 29 (47.5%) patients. CD was
      diagnosed in 29 (47.5%) patients. Four of 61 patients (6.5%) had no symptoms of
      malabsorption. CONCLUSION: All the patients with IDA of unclear genesis must
      undergo serological tests for CD. In high titers of antibodies to AGA and TTG,
      retrobulbar duodenal biopsy is indicated with histological study of small
      intestinal mucosa.

PMID- 16613098
TI  - [Gilbert's syndrome: a clinicogenetic trial].
AB  - AIM: To improve diagnosis of Gilbert's syndrome (GS) basing on functional and
      genetic methods of examination. MATERIAL AND METHODS: GS was diagnosed in 88
      patients aged 15-72 years using clinical and genetic tests. RESULTS: Genotyping
      has detected changes in promotor part of the gene coding
      uridindiphosphateglucuroniltransferase. In homozygous carriers GS was
      characterized by a higher baseline level of bilirubin, distinct response to
      functional tests, frequent combination with essential tremor. In heterozygous
      patients GS often ran latently. CONCLUSION: Four variants of GS course were
      established: dispepsic, asthenovegetative, jaundice, latent. Low-caloric diet
      followed by fenobarbital raised sensitivity and specificity of the test. A
      clinical classification of GS is proposed. The detected disorders of antipirin
      pharmacokinetics allow prognosis of the risk of unwanted reactions to the drugs
      metabolized by monooxigenases of the liver.

PMID- 16613099
TI  - [Hepatic lesion in patients with hepatocerebral dystrophy].
AB  - AIM: To study hepatic affection in hepatocerebral dystrophy (HCD) regarding
      clinical course and duration of the disease. MATERIAL AND METHODS: The records on
      63 HCD patients were studied retrospectively as to early clinical symptoms, onset
      dynamics, biochemical tests for hepatic function, morphological changes of the
      liver, immune and cytokine status, markers of hepatotropic viruses. RESULTS: Six
      variants of HCD course were identified: hepatic (24 patients), endocrine (17
      patients), neurological (12 patients), psychoemotional (5 patients), hemolytic (3
      patients), renal (1 patient). Early hepatitis and hepatic cirrhosis progress were
      characteristic for the hepatic variant. The other variants were characterized by
      hepatic fibrosis, lipofuscinosis, fat dystrophy of the liver. Markers of viral
      hepatitides B, C, G, TT were detected primarily in patients with a hepatic
      variant of HCD. A moderate rise of aminotransferases, immunoglobulins, cytokines
      level indicate weak inflammation in hepatic tissue. Disorders in proteins
      synthesis, hepatic detoxication function reflect changes in the microsomal system
      and endoplasmic network. CONCLUSION: Hepatic lesions in HCD are different.
      Clinical, biochemical, morphological activity and immune status affections were
      most severe in patients with hepatic and endocrine variants of HCD, being the
      least severe in neurological, psychoemotional and hemolytic variants.
      Hepatotropic viruses in some patients deteriorate hepatic lesion caused by copper
      imbalance.

PMID- 16613100
TI  - [A cytokine status in chronic alcoholic and biliary pancreatitis].
AB  - AIM: To determine characteristics of a cytokine status in chronic pancreatitis
      (CP) depending on etiological factor, stage of the disease, complications,
      therapy. Material and methods. 72 patients had chronic alcoholic pancreatitis
      (CAP), 38 patients--chronic biliary pancreatitis (CBP). Control group consisted
      of 20 healthy subjects. RESULTS: At early stages and height of CAP exacerbation,
      concentrations of IL-1beta, IL-6, IL-8, TNF-gamma and TNFalpha were elevated
      (951.1 +/- 104.2 pg/ml; 172.8 +/- 24.3 pg/ml; 432.6 +/- 68.5 pg/ml; 823.3 +/-
      97.5 pg/ml; 158.7 +/- 19.6 pg/ml, respectively). Regenerative processes in CP
      were accompanied with IL-4 elevation to 614.9 +/- 64.6 pg/ml. In CAP without
      complications and with them the levels of cytokines differed significantly. The
      level of TGF-beta1 stimulating development of fibrosis was in CAP patients 627.8
      +/- 92.2 pg/ml, in CAP patients with complications--796.8 +/- 102.5, in the
      controls--40.2 +/- 4.6 pg/ml (p < 0.05). In early stages of CBP exacerbation, IL
      1beta rose to 527.2 +/- 62.7 pg/ml, IL-6--to 80.9 +/- 11.4 pg/ml, IL-8--to 290.4
      +/- 46.8 pg/ml, INF-gamma to 853.3 +/- 91.6 pg/ml; TNF-alpha--to 79.7 +/- 8.3
      pg/ml, TGF-beta1--534.1 +/- 78.4 pg/ml. With attenuation of acute syndromes and
      development ofregeneration, levels of IL-4 went up (226.7 +/- 32.4 pg/ml).
      CONCLUSION: CP is accompanied by increase in cytokine contents depending on the
      etiological factor, variants of course, stage, presence of complications.

PMID- 16613101
TI  - [Use of spironolactone and indapamide in the treatment of low-renin arterial
      hypertension].
AB  - AIM: To compare efficacy of use of the blocker of aldosteron receptors
      spironolactone and diuretic indapamide in low-renin arterial hypertension (AH),
      their action on blood pressure, serum concentrations of sodium, potassium,
      creatinine, plasmic renin activity (PRA), plasmic aldosteron concentration (PAC).
      MATERIAL AND METHODS: The study included 31 females aged 40-60 years with hardly
      correctable AH and high PAC to (PRA) ratio. Biochemical parameters were measured
      before 2-week treatment with indapamide (1.5 mg/day) and spironolactone (25
      mg/day) and after the treatment. Between the courses there was a 2-week interval.
      RESULTS: In AH patients with high PAC/PRA spironolacton reduced AP more
      significantly (-15.5 / -8.2 mmHg) than indapamide (-10.9 / -5.9 mmHg). Indapamide
      lowered potassium serum levels by 0.28 mmol/l (p < 0.05), spironolacton raised it
      by 0.26 mmol/l (p = 0.05). Sodium concentration in the serum reduced only after
      treatment with spironolactone. Both drugs increased blood concentrations of
      creatinine, aldosteron, PRA, but spironolactone was more active. CONCLUSION: In
      treatment-resistant AH it is necessary to perform screening for detection of
      patients with low-renin hypertension. Such patients are effectively treated with
      spironolacton in low doses.

PMID- 16613102
TI  - [Dental diseases and osteoporosis may serve a diagnostic key for celiac disease
      (a case report)].

PMID- 16613103
TI  - [Food allergy and food intolerance: differential diagnosis].

PMID- 16613104
TI  - [Treatment of ischemic heart disease in patients with gastrointestinal diseases].

PMID- 16613105
TI  - [Diagnosis and treatment of intestinal inflammation: a sign of the progress in
      medicine of the XXI century].

PMID- 16613106
TI  - [The role of psychic factor in development of peptic gastroduodenal ulcers].

PMID- 16613107
TI  - [Microhemorheological disorder: characteristics and clinical value].

PMID- 16613108
TI  - [Some aspects of erectile dysfunction pathogenesis and treatment in patients with
      obesity].

PMID- 16613109
TI  - [COPD diagnosis according to a Swedish model. Age-related FEV percent-value gives
      acceptable approximation].

PMID- 16613110
TI  - [Neuraminidase inhibitors are effective in influenza---if administered quickly
      after the debut or as prophylaxis to infected persons].

PMID- 16613111
TI  - [Family planning using contraceptive vaccination. Immunologic infertility gives
      the clue].

PMID- 16613112
TI  - [Medical students experience more stress compared with other students].

PMID- 16613113
TI  - [Was it paradoxal embolism? Cerebellar infarction, patent foramen ovale and APC
      resistance--a controversial combination and and therapeutic challenge].

PMID- 16613114
TI  - [Are healthy persons diagnosed with COPD?].

PMID- 16613115
TI  - [Waran following thrombolysis with Actilyse].

PMID- 16613116
TI  - [Interaction between Waran and cranberry juice].

PMID- 16613117
TI  - [Fibrates, nicotinic acid preparations and muscular pain].

PMID- 16613118
TI  - [No clinical support for the statement that asylum seeking children hav been
      drugged].

PMID- 16613119
TI  - [The "innovative" drug industry].

PMID- 16613120
TI  - [Simvastatin 40 mg as secondary prophylaxis: Effective, tolerable and cost
      efficient!].

PMID- 16613121
TI  - [La Salpetriere--the cradle of modern neurology].

PMID- 16613122
TI  - Competency: ensuring best possible outcomes.

PMID- 16613123
TI  - Flattening the nursing world.

PMID- 16613124
TI  - Faculty matters: Kathleen L Sitzman.

PMID- 16613125
TI  - Strong minds, healing hands, and compassionate hearts: Developing a contemporary
      and creative twist on tradition.

PMID- 16613126
TI  - Creating new futures in nursing education: envisioning the evolution of e-nursing
      education.
AB  - This article discusses the explosion of technology and its impact on nursing
      education in the face of a nurse educator shortage. An attempt is made to answer
      the following questions:What incremental changes in technology do we have now?
      How do we envision technology being used in the future? Four scenarios of
      nontraditional approaches to nursing education are presented. They touch on the
      delivery of education with increased technology and universal access; the teacher
      as educator/mentor/coach; the product, including testing, outcomes, competencies,
      and process; and attracting and keeping human attention. The final section
      focuses on issues to consider as nurse leaders and educators bring nursing
      education into the future.

PMID- 16613127
TI  - Innovations in clinical simulation: Application of Benner's theory in an
      interactive patient care simulation.
AB  - This article introduces the University of Maryland Baltimore School of Nursing
      clinical simulation protocol structure and lessons learned while using this
      protocol in a mandatory learning experience for over 190 adult health students.
      Students use a SimMan manikin in a high-fidelity, interactive clinical simulation
      to provide care to "unstable patients." Benner's concepts regarding the
      performance characteristics and learning needs of nurses with varying levels of
      clinical competency were incorporated into the development of the simulation. The
      simulation provides a positive learning experience in which students refine their
      patient management skills and collaborate with multidisciplinary team members to
      resolve common postoperative problems.

PMID- 16613128
TI  - The Population-Focused Analysis Project for teaching community health.
AB  - New instructional methodologies that foster student inquiry, critical thinking,
      accountability, group work, and self-mastery skills must be created to meet the
      challenges of modern community health nursing. Bold steps need to be taken to
      examine current nursing curricula and institute innovative teaching-learning
      methods to achieve these outcomes. Designing a unique way of providing clinical
      practice in community assessment is one step toward achieving these goals. The
      purpose of this article is to share the development, implementation, and
      evaluation of the Population Focused Analysis Project (PFAP). This new approach
      to community assessment for baccalaureate nursing students links theory and
      clinical practice and provides students with an opportunity to learn about and
      implement the core functions of public health in relation to a selected
      population.

PMID- 16613129
TI  - Evidence-based program requirements: evaluation of statistics as a required
      course.
AB  - A retrospective student record review was conducted to determine how achievement
      in a prerequisite statistics course related to achievement in nursing research
      courses and the overall program for undergraduate and graduate nursing students.
      For undergraduate students (n=218 generic, n=111 RN/BS), the statistics grade was
      associated with 4.3 percent of the variance in research course grades and 6.8
      percent of the variance in graduating grade point average (GPA), controlling for
      entering GPA. For students in accelerated second-degree programs (n=33), there
      were minimal differences in mean research course grades and graduating GPA
      between students with and without prior statistics courses. For master's degree
      students (n=160), higher statistics grades were not associated with graduate
      research course grades. At best, the amount of prediction associated with
      statistics course grades was found to be small and not educationally meaningful.
      The value of statistics as a program requirement for undergraduate or graduate
      nursing students cannot be supported by these analyses.

PMID- 16613131
TI  - The 2005 word of the year: podcast.

PMID- 16613130
TI  - Academic dishonesty, bullying, incivility, and violence: difficult challenges
      facing nurse educators.

PMID- 16613132
TI  - A first step toward reform: results of the Faculty Survey on Innovation.

PMID- 16613133
TI  - Laboratory diagnosis of bloodstream infections caused by extended-spectrum beta
      lactamase-producing E. coli and Klebsiella species.
AB  - Extended-spectrum beta-lactamase (ESBL)-producing organisms are resistant to the
      third-generation cephalosporins commonly used as empirical therapy for a wide
      range of serious infections. It is therefore important for laboratories to offer
      reliable ESBL detection methods. This study compares two combination disc methods
      (Oxoid and Mast Diagnostics) containing cepodoxime with and without clavulanate
      with Vitek 2 for routine detection of ESBLs in Escherichia coli and Klebsiella
      spp. isolated from blood cultures. From December 2003 to April 2005, a total of
      58 potential ESBL-producing isolates (resistant to cefotaxime and/or ceftazidime)
      by BSAC disc susceptibility were tested by the combination discs and Vitek 2. The
      Advanced Expert System, a feature of Vitek 2 reports possible mechanisms of
      resistance, based on interpretive reading of MICs. This study detected 7.4% more
      ESBL-producing isolates by Vitek 2 than by Oxoid disc testing (95% CI: 0.15
      14.7%; P < 0.2) and 31.6% more ESBL-producing isolates were detected by Vitek 2
      than by Mast disc testing, (95% CI: 16.2-46.96%; P < 0.001). Batch-to-batch
      variation was evident in disc performance for both disc types. Thus, use of
      appropriate controls is recommended when testing by the combination disc methods.
      Although no phenotypic test is 100% sensitive and specific, the Vitek 2 was a
      reliable system for ESBL detection; however, it is expensive and interpretation
      of results can be confusing to inexperienced users. Further studies to compare
      Vitek 2 with cefotaxime and ceftazidime combination discs may reveal disc
      methodology for ESBL detection to be a more reliable alternative than using
      cefpodoxime combination discs alone.

PMID- 16613134
TI  - Candida albicans and Candida dubliniensis: comparison of biofilm formation in
      terms of biomass and activity.
AB  - Candida albicans and C. dubliniensis are two species responsible for oral
      candidiasis, especially in immunocompromised patients. Microbial infection is
      preceded by adherence and biofilm formation. Biofilm formation represents the
      most common form of C. albicans in the oral cavity and is considered to be one of
      the most important virulence factors. In this study, the biofilm formation
      ability of C. dubliniensis was compared with that of C. albicans in terms of
      biomass (quantified using crystal violet) and activity (assessed by formazan
      salts formation). Both species formed heterogeneous biofilms; however, species
      and strain variations were seen in the quantification of biomass and activity.
      There was no correlation between pseudohyphae formation and biofilm formation
      capability.

PMID- 16613135
TI  - Stimulatory effects of Antidesma madagascariense on D-glucose, L-tyrosine, fluid
      and electrolyte transport across rat everted intestine, comparable to insulin
      action in vitro.
AB  - Medicinal plants are believed to be an important source of potential therapeutic
      agents. This study investigates the effects of Antidesma madagascariense (AM)
      extract on the transport of D-glucose, L-tyrosine, fluid and electrolytes (Na+
      and K+) across rat everted intestinal sacs. These sacs were mounted in an organ
      bath containing Krebs-Henseleit bicarbonate (KHB) buffer. Experimental findings
      showed that incubation with graded aqueous AM extracts above 0.375 mg/mL
      significantly (P < 0.05) stimulated the mucosal disappearance and serosal
      appearance of glucose and fluid. The concentration of glucose accumulated in the
      intestinal tissues also increased significantly (P < 0.05) compared to that found
      in the controls. Transport of the amino acid L-tyrosine was not significantly
      enhanced (P > 0.05) when incubated with increasing concentrations of AM extract.
      Effects on electrolyte (K+ and Na+) transport were assessed. Na+ uptake and
      transport was significantly enhanced (P < 0.05) when incubated with 0.75 mg/mL AM
      extract; however, K+ transport was not significantly enhanced (P > 0.05). For
      comparison, insulin (1 and 2 units/mL) was incubated in the mucosal solution.
      Aqueous AM extract produced similar stimulatory effects on the transport of
      glucose, fluid and Na+ as were found with insulin. It is hypothesised that
      bioactive phytochemicals such as flavonoids, alkaloids, leucoanthocyanins,
      phenols and saponins from AM leaf extract might interfere with the Na+/glucose
      carrier, thereby enhancing the transport of glucose, Na+ and fluid across rat
      everted intestinal sacs. Thus, AM may represent a possible alternative dietary
      supplement for the treatment of type 2 diabetes.

PMID- 16613136
TI  - Detection of red cell antibodies: comparison of two low ionic strength diluents.
AB  - Various low ionic strength diluents are used routinely for red cell alloantibody
      detection in the antiglobulin test to increase the rate of antibody association
      to antigen, thereby allowing a reduction in the incubation time while achieving
      optimal agglutination. Two commercial low ionic strength diluents (DiaMed ID
      CellStab and Inverclyde LISS) were assessed using the DiaMed-ID LISS Coombs'
      microtube column system, to assess whether or not the choice of diluent
      influences red cell antibody detection. Effects of two low ionic strength
      diluents after 15-min incubation were assessed in 150 samples containing a wide
      range of typical red cell alloantibodies. Inverclyde LISS gave significantly
      higher reaction strengths in 25% of samples when compared with the same red cells
      suspended in ID-CellStab. Variation in reaction strengths ranged from 1+ to 2+,
      using Inverclyde LISS versus CellStab. Of 131 red cell alloantibodies directed
      against Rh, Kell, Kidd and Duffy antigens, Inverclyde LISS detected 90% after 15
      min incubation, whereas 83% were detected with CellStab. This study suggests that
      Inverclyde LISS provides better red cell alloantibody detection than does ID
      CellStab, and this may be due to the higher ionic strength of ID-CellStab.

PMID- 16613137
TI  - Microorganisms mistaken as vancomycin-resistant Staphylococcus aureus at a cancer
      hospital in Lahore, Pakistan: their true identity revealed.

PMID- 16613138
TI  - Antibiotic resistance and identification of uncommon Gram-negative bacteria
      isolated from sputum of adult patients with cystic fibrosis.

PMID- 16613139
TI  - Analysis of 16S-23S intergenic spacer regions of the rRNA operons in Tsukamurella
      pulmonis.

PMID- 16613140
TI  - Detection of Dientamoeba fragilis and Blastocystis hominis using a simple
      staining method.

PMID- 16613141
TI  - Human immunodeficiency virus and hepatitis C co-infection in sub-Saharan West
      Africa.
AB  - Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      is becoming a major global problem, leading to increased morbidity and mortality
      in developed countries. Co-existence in sub-Saharan West Africa of a high
      prevalence of HIV and HCV, which share similar behavioural risk factors and modes
      of transmission, must be seen in the broader context of an emerging third
      epidemic of HIV and HCV co-infection, as many factors that may affect the spread
      of HIV and HCV co-infection are endemic in the continent, including host factors
      such as sexual behaviour, presence of other sexually transmitted diseases, female
      and male circumcision status, percutaneous and perinatal exposure, and poverty.
      This review examines the epidemiology, risk factors and transmission of HIV and
      HCV co-infection and draws attention to the possible emergence of an epidemic of
      HIV and HCV co-infection in the region.

PMID- 16613142
TI  - [Avoidance of patient-prosthesis mismatch].
AB  - To minimize the incidence of patient-prosthesis mismatch (PPM), we have routinely
      adopted aortic root enlargement to avoid PPM for patients with small aortic
      annulus. The aim of this study was to review our strategy of avoiding PPM. The
      Carpentier-Edwards Perimount (CEP) valves were implanted in 53 patients who were
      mostly aged over 65 and the St. Jude Medical (SJM) mechanical valves were used in
      128 patients aged under 65. A standard 21-mm SJM valve was used in only 3
      patients and no 19-mm valves were employed. However, 19-mm CEP valves were used
      in 12 patients with a small body surface area (1.43 +/- 0.14 m2). Of these, 26
      patients (14.4%) who had a small aortic annulus and 24 patients aged under 65
      underwent aortic root enlargement. No patient receiving an SJM valve had an
      projected indexed effective orifice area (EOAI) < or = 0.85 cm2/m2 because of
      performing aortic valve replacement (AVR) with annular enlargement and only 2
      (3.8%) out of 53 patients receiving CEP valves developed PPM. Consequently, the
      prevalence of PPM was 1.1% in this series. The prevalence of PPM was low in
      patients over 65 years old with a relatively small body size who received
      bioprosthetic valves. A pericardial bioprosthesis was considered to be an
      appropriate valve in older population with regard to avoiding PPM. In patients
      under 65 years old with a small annulus, the first choice for avoiding PPM is
      aortic annular enlargement, which may be avoided by high performance mechanical
      valves with larger EOA.

PMID- 16613143
TI  - [Aortic valve replacement for the small aortic annulus].
AB  - Aortic valve surgery for the small aortic annulus is still challenging for
      surgeons. Recently, the new types of high performance prosthesis have been
      developed and the chance of an aortic root enlargement (ARE) is decreasing. In
      this study, we propose the ideal strategy of the aortic surgery for the small
      aortic annulus. We analyzed the clinical records of 158 patients who underwent
      aortic valve replacement from August 1999 to October 2005 in our institution. The
      small aortic annulus was observed in 38 patients (24%). Fourteen patients of this
      group underwent ARE. Patient-prosthesis mismatch (PPM) was less frequently
      observed in patients with ARE compared to those without ARE. The additional time
      required for ARE was not considerable, and neither ischemic time nor
      cardiopulmonary bypass time was significantly prolonged by ARE. In conclusion, we
      have to select a prosthesis with sufficient orifice area to avoid PPM, otherwise
      we should choose an option of ARE. For this consideration, we definitely need the
      chart that demonstrates the relationship between the nominal size of various
      types of prostheses and the size of a patient's annulus that those prostheses
      actually fit.

PMID- 16613144
TI  - [Aortic root enlargement in elderly patients].
AB  - From January 2003 to June 2005, 12 elderly patients with severe aortic stenosis
      underwent aortic root enlargement (ARE) by Nicks procedure. Their ages ranged
      from 74 to 87 with a mean of 79.3. Stented bioprosthesis were used in 11 cases.
      There was no death. Cardiothoracic ratio on chest X-ray decreased from 59.4 to
      53.6% and New York Heart Association (NYHA) functional class improved from 3.4 to
      1.3. Echocardiography also showed remarkable improvement, in peak pressure
      gradient (PG) from 98.3 to 20.7 mmHg, in left ventricular mass index (LVMI) 181
      to 137 g/m2. LVM and LVMI regression rates were 25.3 and 22.3%, respectively.
      Comparative study of those with ARE alone and those with combined operation
      showed much hazardous effect in the latter, but no significant difference in
      echocardiographic findings postoperatively. ARE by Nicks procedure, if it could
      be performed without concomitant procedure, is a safe and effective option also
      in elderly patients with small aortic annulus.

PMID- 16613145
TI  - [Surgical technique of aortic valve replacement for small aortic annulus in
      elderly patients].
AB  - Recent reports have shown that aortic valve replacement in elderly patients over
      65 years with atherosclerotic aortic stenosis and a small aortic annulus is
      possible by using a small sized bioprosthesis (Carpentier-Edwards pericardial
      valve). Here we present out surgical technique. Firstly, the native calcified
      aortic valve was removed completely to gain total exposure of the surrounding
      aortic root and sinus of Valsalva like Bentall procedure. Secondly, a small sized
      bioprosthesis was implanted with intermittent noneverting mattress 2-0 sutures
      with spaghetti and small polytetrafluoroethylene (PTFE) felt. Aortic annulus is
      the dilated by inserting Hegar dilator sizing from 25 to 27 mm. Therefore, aortic
      valve replacement for small aortic annulus in intra- or supra-annular position
      should be easily accomplished. Good surgical results and hemodynamic state were
      achieved in 25 consecutive cases using this technique.

PMID- 16613146
TI  - [Advantage of supra-annular patch enlargement in aortic stenosis with a small
      aortic annulus].
AB  - BACKGROUND: We routinely perform supra-annular patch enlargement as a strategy to
      avoid patient-prosthesis mismatch (PPM) in patients with a small aortic annulus
      who are undergoing aortic valve replacement (AVR). METHOD: We performed a
      retrospective review of 128 consecutive single AVR patients from 1999 to 2005. Of
      these, 34 patients underwent supra-annular patch enlargement. The enlargement was
      selectively performed in patients at risk of PPM. This involved patch extension
      of the aortotomy just above the annulus of noncoronary sinus, and valve
      implantation with stitches placed directly on the patch. Along with this
      procedure, AVR with a valve size appropriate to body surface area (BSA) was
      performed. RESULT: Of these patients, 74% were female and the mean BSA was less
      than 1.50 m2. The enlargement required an average of 33 minutes of additional
      aortic clamp time. The 30-day mortality was 0%. A favorable hemodynamic outcome
      was achieved. CONCLUSION: Our results show that supra-annular patch enlargement
      can be performed with minimal added risk, relative to standard root enlargement
      and a satisfactory hemodynamic status can be achieved by employing this
      procedure.

PMID- 16613147
TI  - [Apicoaortic conduit insertion for elderly patients with acquired aortic stenosis
      and small aortic annulus].
AB  - BACKGROUND: Patients with critical aortic stenosis, a heavily calcified aorta,
      and a small aortic annulus are at an increasing risk of complications during a
      conventional aortic valve replacement (AVR) procedure. Insertion of an
      apicoaortic conduit (AAC) can be an alternative to AVR in such situations. This
      study is a review of our experiences with AAC in elderly patients with acquired
      aortic stenosis. METHOD: From 2001 to 2005, 7 elderly patients (mean age of 81 :
      range 74 to 87) underwent an AAC insertion for severe symptomatic aortic stenosis
      with a small aortic annulus (mean annulus size 17.9 mm). Preoperatively, all were
      symptomatic, with 4 rated as New York Heart Association (NYHA) functional class
      IV, 2 as class III, and 1 as class II. In addition, 3 patients had severe
      congestive heart failure with mechanical ventilation and received a high dose
      administration of catecholamine, and 1 had undergone coronary artery bypass
      grafting (CABG) previously. RESULT: The AAC insertions were performed under a
      cardiopulmonary bypass through a left thoracotomy in 6 patients, while 1 patient
      underwent the procedure without a cardiopulmonary bypass. Distal anastomoses were
      performed in the descending thoracic aorta with a partial occluding clamp. A
      composite woven Dacron conduit with a stented biological valve was used in 2
      cases, and a woven Dacron conduit with a stentless bioprosthesis was used in 5.
      Two patients underwent a concomitant CABG. There was 1 hospital death due to
      obstructive ileus 4 months after the operation. One patient who had been in a
      shock state preoperatively had hypoxic encephalopathy due to inoperative severe
      hypotension. Postoperative echocardiography showed relief of the left ventricle
      aortic gradient in all patients. After a mean follow-up period of 22 months,
      there was no late death, while 3 patients were readmitted due to congestive heart
      failure. Further, 1 of the patients was rated as NYHA class I, 1 as class II, and
      2 as class III. CONCLUSION: An AAC procedure was found to be an acceptable
      alternative for elderly patients who had a high-risk of complications with the
      standard procedure.

PMID- 16613148
TI  - [Aortic valve replacement for calcified aortic valve and annulus with ultrasonic
      decalcification].
AB  - We conducted ultrasonic decalcification on calcified annulus in patients with
      aortic stenosis (AS) using an ultrasonic operator, Sonopet (UST 2001) prior to
      aortic valve replacement (AVR). We studied the reliability of this method.
      SUBJECT AND METHOD: From January 2002 to August 2005, AVR was conducted for AS
      using the Sonopet in 45 patients, comprising of 18 male and 27 female subjects.
      The mean age was 73.3 +/- 9.7. RESULT: Artificial valves were successfully
      inserted at the intra-annular level in 37 patients and at the supra-annular level
      in 8 patients without conducting annular enlargement. In the patients with narrow
      annuli of less than 19 mm (23 patients), the preoperative mean annular diameter
      was 18.2 +/- 1.0 mm, but significantly larger artificial valves with an average
      diameter of 19.3 +/- 1.5 mm (p=0.003) were successfully inserted. CONCLUSION: AVR
      was proved to be safe and easy by previous ultrasonic decalcification of the
      annuls using the Sonopet. This method was very useful because it required no
      enlargement of aortic annulus.

PMID- 16613149
TI  - [Long-term results of conventional aortic valve replacement for small aortic
      annulus].
AB  - We studied cardiac function, clinical outcome and quality of life (QOL) long
      after aortic valve replacement for pure aortic stenosis. Forty-four patients in
      small group [St. Jude Medical (SJM) 17 HP, 19 A], and 69 patients in non-small
      group (19 HP, 21 A, 23 A) operated on from 1984 to 2004 were enrolled in this
      study. We assessed the clinical data, aortic pressure gradient, left ventricular
      mass index (LVMI), and ejection fraction (EF) by preoperative and postoperative
      echocardiography. Moreover to evaluate QOL after the operation, we performed SF
      36 used for the evaluation of health and QOL worldwide. Mean follow-up is 7.1 +/-
      4.8 years in small group, and 6.8 +/- 4.6 years in non-small group. There were 2
      hospital deaths in small group, and 1 in non-small group. The actual survival
      rate at 10-year were 89.2% in small group, and 85.6% in non-small group. There
      was no significant difference in hospital mortality, LVMI, long-term survival
      rate, and the scores of SF-36 between the 2 groups. The use of small sized
      prosthetic valves in patients with small aortic annulus might be justified when
      there is no patient-prosthesis mismatch.

PMID- 16613150
TI  - [Clinical outcome of aortic valve replacement with 19-mm prosthetic valve in
      elderly patients].
AB  - From 1979 to June 2005, 90 patients aged 65 or older underwent aortic valve
      replacement with 19-mm prosthetic valve. They were 84 women and 6 men, with a
      mean age of 74. The mean body surface area was 1.35 m2. Bioprosthetic valves were
      implanted in 77 patients (85.6%). In-hospital mortality was 2.2% (2 of 90). There
      were 13 late deaths. New York Heart Association (NYHA) functional class improved
      to class I in most of survivors. Survival rates for 5 and 10 years were 84.9 and
      71.2%, respectively. The outcome of aortic valve replacement with 19-mm
      prosthetic valve in elderly patients was excellent.

PMID- 16613151
TI  - [Patient-prosthesis mismatch after aortic valve replacement; tolerable lower
      limit of indexed effective orifice area].
AB  - This study was aimed at determining the tolerable lower limit of the indexed
      effective orifice area (EOAI) to prevent patient-prosthesis mismatch (PPM).
      Echocardiography was performed in 87 consecutive patients who underwent aortic
      valve replacement (AVR). EOAI was estimated for each type and size of prosthesis
      and used to define PPM as moderate if >0.65 cm2/ m2 and < or = 0.85 cm2/m2, and
      severe if < or = 0.65 cm/m2. Aortic valve pressure gradients, left ventricular
      dimensions, and outcome (in-hospital and 1-year) were analyzed in the presence or
      absence of abnormal gradients (> or = 40 mmHg) to assess the influence of a small
      valve (19 mm or less labeled size). Severe PPM was found in 23% of all patients,
      and 50% of the severe PPM patients had an abnormal gradient. There was 1 death
      and 1 brain damage from ventricular fibrillation because of severe PPM in the
      abnormal gradient group with a small valve. In PPM patients with a small valve,
      EOAI (0.61 +/- 0.04 vs 0.69 +/- 0.07) and preoperative interventricular septal
      thickness (IVST : 16.4 +/- 2.6 mm vs 13.5 +/- 1.5 mm) were significantly
      different between abnormal and normal gradient groups. An EOAI > or = 0.69
      appeared to be tolerable in patients with a lower level of hypertrophy (IVST < 16
      mm).

PMID- 16613152
TI  - [Diastolic heart failure in patients with aortic valve disease].
AB  - From March 2002 to August 2005, 53 patients with age between 30 and 86 underwent
      surgical treatment for aortic valve disease. Preoperative diastolic heart failure
      was observed in 15 cases (28.3%). Operative procedures consisted of aortic valve
      replacement (AVR) in 42 cases [AVR and mitral valve replacement (MVR) in 3],
      aortic valve plasty (AVP) in 2, and aortic root replacement in 4. Concomitant
      procedures included maze procedure in 2 cases, coronary artery bypass grafting
      (CABG) in 6, mitral valve surgery in 15, and tricuspid valve annuloplasty (TAP)
      in 8. There were 7 cases for patient-prosthesis mismatch (PPM) [13.2%]. There
      were 2 hospital deaths (both were low-output syndrome). Among the surgical
      survivors, there were 2 late cardiac-related complications (all cases were
      cardiac failure). There was no recurrence or re-operation. Although all cases had
      severe diastolic failure, their systolic function was almost normal. Our study
      suggested that in patients with aortic valve disease, not PPM but diastolic heart
      failure correlated strongly with postoperative event and survival.

PMID- 16613153
TI  - [Aortic valve replacement in elderly patients with small aortic annulus; is the
      indexed effective orifice area important?].
AB  - We sought to determine whether the small indexed effective orifice area (EOAI)
      increased mortality and morbidity after aortic valve replacement (AVR) in
      patients over 75 years of age. From May 1999 to July 2005, 77 patients underwent
      isolated AVR for aortic stenosis. They were divided into 3 groups (S-EOAI : EOAI
      < or = 0.7 cm2/m2, M-EOAI : 0.7 cm2/m2 <EOAI < or = 0.85 cm2/ m2, L-EOAI :
      0.85cm2/m2 <EOAI) for evaluation. We examined the body surface area (BSA), EOAI,
      and the left ventricular (LV) mass index (LVMI). We found that patients with S
      EOAI had less symptomatic improvement (p <0.05, vs L-EOAI) and LV mass regression
      (p< 0.01, vs L-EOAI). But, their average New York Heart Association (NYHA) class
      was improved significantly (2.3 +/- 0.8 vs 1.8 +/- 0.7 : preoperative vs
      postoperative, p=0.001). Furthermore, severe patient-prosthesis mismatch (PPM)
      had no significant negative impacts on the freedom of valve-related complications
      (75.1% : S-EOAI group vs 92.0% : L-EOAI group) and the 5-year survival (84.9% : S
      EOAI group vs 87.8% : L-EOAI group). In elderly patients, the average NYHA class
      was 1.9 +/- 0.6 postoperatively (p<0.0001 vs preoperative) and the LVMI showed
      significant regression (p<0.0001) despite an average EOAI of 0.73 +/- 0.13
      cm2/m2. It is important to consider whether the benefits of avoiding PPM overcome
      the drawbacks of other complicated techniques. In this study, we found that
      moderate PPM (0.7 cm2/m2 < or = EOAI) is acceptable to elderly patients.

PMID- 16613154
TI  - [Evaluation of aortic valve replacement involving small severely calcified aortic
      annulus in elderly patients].
AB  - We performed aortic valve replacement in 24 patients aged over 70 with small
      calcified valves. The surgical management of such patients remains controversial
      as the extensive calcification compromises implantation. Hence, we used an
      ultrasonic debridement instrument to remove calcium and selected a small
      prosthesis with the largest possible orifice without enlargement of the aortic
      annulus. Echocardiography showed significant reductions in left ventricular mass
      index compared with preoperative values. Early and mid-term prognosis has been
      relatively good.

PMID- 16613155
TI  - [Mediastinal emphysema after a punch on the back; report of a case].
AB  - A 19-year-old man was punched on the back, and anterior chest pain appeared about
      3 hours after injury. The patient was consulted a physician complaining of
      anterior chest pain. On chest X-ray, mediastinal emphysema was suspected, and
      transferred to our hospital. Chest computed tomography (CT) revealed mediastinal
      emphysema. On esophageal radiography and bronchofiberscopy, no abnormal findings
      were detected. Conservative therapy was conducted, and symptoms had gradually
      improved. On the 8th hospital day, mediastinal emphysema was improved on chest
      CT. The patient was discharged on the 10th hospital day. The most frequent cause
      of mediastinal emphysema after trauma is traffic or downfall accident, and no
      report on this condition after the punch on the back was found.

PMID- 16613156
TI  - [Descriptions of treatment in the Hippocratic Collection with special reference
      to surgery, particularly for urinary stones].
AB  - PURPOSE: I analyzed mentions of treatment in the Hippocratic Collection.
      MATERIALS AND METHODS: I examined quantitatively mentions of treatments in the
      Hippocratic Collection (Roeb edition, Otsuki edition, and Kon edition) to compare
      preferences for therapy between the Kos and Knidos schools. RESULTS: Treatments,
      mentioned in 2,687 passages, were medical in 2,319 (86%), and surgical in 368
      (14%). These 2,687 descriptions included 1,023 (38%) from the Kos, 1,261 (47%)
      from the Knidos school, and 403 (15%) from unspecified schools. Of the 2,319
      descriptions of medical treatment, 560 (24%) referred to medicines and 466 (20%)
      to diet, followed by baths, vapor baths, exercise, running, walking, warm
      applications, and others. The 368 surgical descriptions involved traction and
      adjustment for treating fractures of bones or dislocation of joints in 166 (45%)
      and surgery using knife or fire in 202 (55%). Of the latter 202 mentions, 87
      (43%) referred to incision with knife, 74 (37%) to cauterization and 73 (37%) to
      bloodletting. Diet, exercises, running, walks, traction, adjustment and
      bloodletting were mentioned more frequently by the Kos school than the Knidos
      school, while medicines, baths, vapor baths (for gynecological diseases) and
      incision were mentioned more frequently by the Knidos school (chi-squared test, p
      < 0.01). Medicines, diet, baths, warm applications, and incision over the kidney
      were mentioned among treatments for urinary stones, but cystolithotomy was not.
      Hippocates stated in "Aphorisms" that diseases that medicines do not cure can be
      cured by the knife. He also, stressed that any one intending to practice surgery
      for wounds arising in military service must serve in the army. CONCLUSIONS: A
      large number of medical treatments were mentioned in Hippocratic Collection,
      while surgical treatments also were emphasized. Hippocrates warned beginning
      doctors not to used unproven treatments for urinary stone in the introduction to
      the "Oath", but did not forbid surgical treatments.

PMID- 16613157
TI  - [Clinical value of primary decompression operation for unilateral ureterocele
      with complete duplex system].
AB  - PURPOSE: To assess a value of decompression operation for a unilateral
      ureterocele with a complete duplex system as an initial procedure. METHODS: We
      reviewed records of 33 pediatric patients with a unilateral ureterocele in a
      complete duplex system who underwent decompression operation between 1987 and
      2000. We checked the patient operative age, followup period, position of the
      ureterocele, type of decompression operation, and additional operation.
      Furthermore we also checked postoperative vesicoureteral reflux (VUR) in patients
      who underwent transurethral incision (TUI). RESULTS: Mean operative age and
      followup period were 6 months old and 82 months. Of the patients, 22 underwent
      TUI and 11 underwent upper moiety operation (UMO). In the TUI group, 14 (63.6%)
      had postoperative VUR and 13 (59.0%) underwent additional operations. These rates
      were higher in the patients with ectopic ureteroceles than with intravesical
      ureteroceles. Most additional operations were undergone for the patients with
      postoperative VUR in TUI group by lower complete reconstructions without UMO. All
      patients with non-functioning upper moiety underwent heminephrectomy at the
      additional operations. In the other hand, in the UMO group, 3 (27.3%) had
      additional operation because of persistent VUR which was found preoperatively in
      lower moiety or contralateral renal unit. CONCLUSION: TUI was useful approach as
      an initial procedure for intravesical ureteroceles because of low additional
      operation rate. For ectopic ureteroceles with functioning upper moiety, TUI was
      high additional operation rate, but it was more useful initial operation of two
      staged operation than UMO because of avoiding UMO, like heminephrectomy, at
      additional operation. UMO was low additional operation rate for ectopic
      ureteroceles without preoperative VUR of renal unit excluding upper moiety.
      Especially heminephrectomy was a useful approach as an initial procedure if upper
      moiety was non-functioning.

PMID- 16613158
TI  - [Assessment criteria of lower urinary tract symptom severity for general
      practitioners].
AB  - OBJECTIVES: We conducted a preliminary study to examine the validity of
      assessment criteria of lower urinary tract symptoms (LUTS) severity for general
      practitioners (GPs). MATERIALS AND METHODS: This study included 194 patients with
      LUTS, who visited the urology clinics in three hospitals. In 177 who completed
      International Prostate Symptom Score (I-PSS), International Consultation on
      Incontinence Questionnaire : Short-Form (ICIQ-SF), frequency-volume chart,
      uroflowmetry and post-void residual urine measurement, three overall grades
      (mild, moderate and severe) of LUTS were determined using the newly-developed
      assessment criteria for GPs. The relationship between diagnoses and treatments by
      the urologists, and overall LUTS grades were examined. RESULTS: All of the 70
      patients with "severe" grade and 68 (94%) of 72 with "moderate" grade were
      diagnosed as having urination problems. Sixty-eight (97%) with "severe" grade and
      64 (89%) with "moderate" grade were treated with fluid restriction, behavioral
      therapy, and/or drug therapy. Of 35 with "mild" grade, 17 (49%) were diagnosed as
      having normal urination. In this grade, eight patients (23%) were treated with
      fluid restriction and 15 (43%) with drug therapy. CONCLUSIONS: This preliminary
      study revealed that our criteria of LUTS severity for GPs were useful to
      determine whether the elderly patients should be treated or not. It is necessary
      to examine the validity of the criteria in a model in which GPs participate.

PMID- 16613159
TI  - [Histopathological changes due to transurethural microwave thermotherapy
      associated with androgen deprivation therapy in patients with localized prostate
      cancer].
AB  - PURPOSE: The 2nd generation transurethral microwave thermotherapy (TUMT),
      equipped with high energy microwave generator and urethral cooling device is
      widely accepted as an less invasive effective modality to treat benign prostatic
      hyperplasia. For prostatic cancer, however, it is generally estimated as
      insufficient because of limitation in penetration of microwave into deep
      prostatic tissue. In this study, we examined histopathologic changes after
      androgen deprivation theraphy (ADT) and TUMT. PATIENTS AND METHODS: Ten patients
      with localized prostate cancer underwent ADT for 3 months, and then TUMT was
      proceeded using Urowave (Dornier MedTech GmbH). Additional 3 months after TUMT
      and continued ADT, TURP in radical fashion was performed in all the patients, and
      all the resected chips were submitted for pathological study. RESULTS:
      Significant reduction in prostate volume was noted after NHT for 3 months from
      37.4 +/- 9.6 ml to 22.0 +/- 5.6 ml. The pathological study of resected chips
      revealed progressive fibrotic changes without viable cancer cells in 9 of 10
      patients. In 1 patient, however, some remnant of carcinomatous foci were noted in
      a resected chip from the middle lobe of the prostate. CONCLUSION: Although the
      number of patient is limited and longer follow-up is needed, the results in
      present series was interested and worth considering.

PMID- 16613160
TI  - [Endoscopic trigonoplasty II for primary vesico-ureteral reflux].
AB  - PURPOSE: We report a technique and outcome of endoscopic trigonoplasty II (ET
      II), anti-reflux surgery via a transvesicostomy transurethral approach and
      discuss its usefulness. MATERIALS AND METHODS: Fifteen female patients, aged 5 to
      64, with 23 refluxing ureters (grade I : 5, II : 2, III : 14, IV : 2) underwent
      the ET II. The principle of this surgery is tightening the muscular backing and
      elongating the intramural ureter. The operation consists of three steps: 1) two 5
      mm locking trocars are placed into the bladder, 2) irrigating with 3% D-sorbitol
      solution, the bladder wall is incised upward along each side of the ureter using
      a resectoscope, to make a 2 to 3 cm U-shaped bladder flap including the ureter,
      3) under a pneumobladder, the incised wall is sutured to make a muscular bed with
      a needle-holder via the urethra and forceps via the abdominal trocar. The U
      shaped flap is fixed with two distal anchor sutures and four additional mucosal
      sutures. Urethral catheter is indwelled and the operation is finished. In recent
      four cases, we closed the tracts endoscopically. RESULTS: The average operative
      time was 144 minutes per ureter. In one patient with unilateral reflux, we
      switched to open surgery because of bleeding. Of 22 refluxing ureters, the reflux
      disappeared in 18 ureters (82%) and improved grade III to I in 1 ureter (5%)
      after 3 months and disappeared in 19 ureters (86%) after 12 months
      postoperatively. Ureteral injury was occurred in 3 patients during the
      transurethral incision of the bladder. Though we repaired it by placing a double
      J stent in the 2 patients, reflux recurred in 12 months postoperatively in one of
      them. In the other patient cystoscopy revealed a vesicoureteral fistula in the
      injured portion. She subsequently underwent successful open Politano-Leadbetter
      ureteroneocystostomy. The average duration of indwelling catheter was shortened
      from 4.3 to 3.0 days by closing the tracts endoscopically. CONCLUSIONS: The
      overall cessation rate of the ET II was inferior to those of open anti-reflux
      surgeries or laparoscopic extravesical ureteral reimplantation. We do not
      recommend ET II for vesicoureteral reflux.

PMID- 16613161
TI  - [Clinical analysis of 1,000 patients with prostate cancer].
AB  - OBJECTIVES: Treatment outcomes for prostate cancer in our hospital were reported.
      MATERIALS AND METHODS: We analyzed 1,009 patients with prostate cancer treated at
      Niigata Cancer Hospital between 1983 and 2003. RESULTS: As for the clinical
      stage, 20 cases belonged to Stage I, 367 cases to Stage II, 269 cases to Stage
      III and 353 cases to Stage IV. The overall 5-year survival rate of the all 1,009
      cases was 59.0%, comprising 78.2% for stage I, 82.0% for Stage II, 76.0% for
      Stage III and 30.0% for Stage IV cases. Disease-specific 5-year survival rates
      for Stage I, II, III and IV were 100%, 96.8%, 89.3% and 41.1% respectively. In
      Stage III patients, the radiotherapy (with endocrine therapy) group showed longer
      cause-specific survival than the endocrine therapy group (p = 0.0056).
      CONCLUSIONS: Our result suggest that the radiotherapy with endocrine therapy is
      useful for Stage III prostate cancer.

PMID- 16613162
TI  - [Case report of advanced renal cancer that showed different responses to the
      alteration of therapeutic cytokines].
AB  - We report a case of advanced renal cancer that showed different responses to the
      alteration of therapeutic cytokines. A 73-year-old man presented with
      asymptomatic macrohematuria, and was diagnosed as right renal cancer (11 x 9 x 9
      cm in diameter) with metastases to abdominal and mediastinal lymph nodes
      (cT3bN2M1, stage IV). Transluminal embolization of the right renal artery was
      performed, and then he was treated by intramuscular administration of natural
      human interferon (IFN)-alpha (Sumiferon; 6 x 10(6) units) three times a week.
      Four months later, lymph node metastases enlarged, and human interleukin-2
      therapy (intravenous administration; 1.4 x 10(6) units) was initiated instead of
      IFN-alpha. However, lymph node metastases further enlarged and multiple lung
      metastases newly appeared in 5 weeks after the alteration of the therapy. Then,
      the treatment was switched to intramuscular administration of another natural
      human IFN-alpha (OIF; 5 x 10(6) units) three times a week. In 3 months after OIF
      administration, all lung metastases disappeared. Lymph node metastases have shown
      no progression for 9 months after the switch to OIF. Different responses to the
      two types of IFN-alpha in this case may be caused by the difference in the
      composition of IFN-alpha subtypes. Alteration of therapeutic cytokines,
      especially a switch from one type to another IFN-alpha may be one of worth
      attempts even if other cytokines are not effective.

PMID- 16613163
TI  - [Case of proximal-type epithelioid sarcoma of the perineum].
AB  - A 31-year-old man was referred to our department for investigation and treatment
      of a rapidly-growing mass in the perineal region. MRI showed a periurethral tumor
      in the perineal region measuring 3.5cm in maximum diameter and bilateral inguinal
      lymph nodes enlargement. Therefore, the tumor was extirpated immediately with
      bilateral inguinal lymphadenectomy. The pathological examination with
      immunohistochemistry revealed that the tumor was proximal-type epithelioid
      sarcoma. Multidisciplinary therapy with irradiation, chemotherapy, and tumor
      ablation with a microwave tissue coagulator, was not effective for local
      recurrence and metastasis, and finally he died of progressive disease 14 months
      after the operation. Epithelioid sarcoma originating from the thigh or trunk is
      classified into the proximal-type, which shows significantly poorer prognosis
      than the distal-type that develops in the distal extremities. The proximal-type
      epithelioid sarcoma of the perineum is rare and, to our knowledge, the present
      report is the fourth case in the Japanese literatures.

PMID- 16613164
TI  - [Primary clear cell carcinoma of the ureter: a case report].
AB  - In September 2003, a 58-year-old woman complained of bladder irritation and
      urinary frequency. She was admitted to a nearby hospital, and an evaluation was
      performed. Urine cytology revealed a class V, and a tumor was detected in the
      lower left ureter with mild hydroneprhosis of the left kidney. We performed a
      left ureteronephrectomy with partial cystectomy in April 2004. The pathological
      diagnosis was clear cell carcinoma with small foci of conventional urothelial
      carcinoma of the left ureter (pT3pN0, G3 > G2, INFgamma). And now she lives well
      without recurrence in August 2005. This is the first case report of clear cell
      carcinoma of the ureter in Japan.

PMID- 16613165
TI  - [Robustness and plasticity of chromatin that is organized functionally in the
      nucleus].

PMID- 16613166
TI  - [Nuclear and chromatin dynamics].

PMID- 16613167
TI  - [Dynamic organization of chromatin in DNA repair].

PMID- 16613168
TI  - [Chromatin dynamics in gene rearrangement].

PMID- 16613169
TI  - [Dynamics of the kinetochore proteins which target to the chromatin of
      centromeres].

PMID- 16613170
TI  - [Discovery of a novel BMP antagonist, ectodin, and its role in tooth
      morphogenesis].

PMID- 16613171
TI  - [ABC proteins move lipids].

PMID- 16613172
TI  - [Dynamics and function of actin-binding proteins in excitatory synapses].

PMID- 16613173
TI  - [Enigma in the physiological role of hexacoordinate globins: an insight from
      structural point of view].

PMID- 16613174
TI  - [Regulation mechanism of Na+ H+ exchanger by novel calcium binding proteins].

PMID- 16613175
TI  - [Detection of coronary unstable plaque by radionuclide imaging].

PMID- 16613176
TI  - [Definition and pathophysiology of acute coronary syndrome].
AB  - Acute coronary syndrome is a clinical state induced by the thrombosis following
      the rupture of unstable atherosclerotic plaque. Atherosclerotic plaque increases
      its vulnerability by the accumulation of foam cells, inflammation, oxidative
      stress, and apoptosis of vascular wall cells including macrophage. Inflammation
      and oxidative stress stimulates macrophages to produce matrix metalloproteinase
      (MMP), which degrades extracellular matric proteins and causes thinning of the
      fibrous cap. When the fibrous cap of the plaque tears, thrombogenic lipid core is
      exposed to blood, and platelets accumulate at the site, resulting in the
      significant reduction of coronary blood flow. Treatment of acute coronary
      syndrome patients should be focused on the stabilization of the plaque as well as
      vasodilatation, oxygen supply, or control of hemodynamics.

PMID- 16613177
TI  - [Progress in the diagnosis and treatment of acute coronary syndromes].
AB  - As the pathogenesis of acute coronary syndromes (ACS) has been well increasingly
      defined, there has been enormous progress in the diagnosis and treatment of ACS
      during the past 50 years. The previous terminology referring to the heterogeneity
      of the disease has shifted toward a unifying concept encompassing the wide
      spectrum of manifestations of ACS, subdivided for the purpose of therapeutic
      considerations into ST elevation myocardial infarction (MI), and non ST elevation
      ACS with or without cell necrosis (utilizing troponins), namely non ST elevation
      MI or unstable angina. The advent of coronary care units and the results of
      randomized clinical trials on reperfusion therapy, thrombolysis or percutaneous
      coronary intervention, and medical treatment with various pharmacological agents
      have substantially changed the therapeutic approach, and decreased in-hospital
      mortality.

PMID- 16613178
TI  - [Epidemiology of acute coronary syndrome].
AB  - We reviewed epidemiological findings of acute coronary syndrome (ACS) in Japan.
      Japan has the lowest mortality and morbidity of ACS in the world. However, the
      crude mortality of acute myocardial infarction in 2003 increased approximately as
      twice as that in 1970, most likely due to an aging of population. More
      importantly, several Japanese prospective studies have failed to demonstrate the
      decline of the age-adjusted incidence of ACS despite the obvious reduction of ACS
      incidence caused by the intervention to the risk factors. Particularly, one study
      implied the increase of ACS patients aged more than 80. Given that the prevalence
      of dyslipidemia, diabetes, and obesity has increased in Japan, we should endeavor
      to modify these risk factors, especially in the elderly.

PMID- 16613179
TI  - [Mechanisms of coronary plaque formation and disruption].
AB  - We review here the evolutional understanding of the pathophysiology of chronic
      and acute phase of coronary artery disease (CAD). Although we previously
      considered CAD as a cholesterol storage disease, we currently understand that
      atherosclerosis is an inflammatory disorder and inflammation plays a major role
      in all stages of atherogenesis. We formerly focused our attention on luminal
      narrowing due to the atheroma. However, we now recognize the need to attend to
      non-obstructive lesions and their biological attributes as well. Moreover, plaque
      disruption is thought to occur due to, not only local changes in the plaque
      itself, but also systemic changes in the patient. Thus, treatment of CAD should
      involve the approach of mechanical revascularization and systemic preventive
      intervention.

PMID- 16613180
TI  - [Acute coronary syndrome related factors].
AB  - Dysruption of vulnerable plaque is a major cause of acute coronary syndromes,
      including acute myocardial infarction and unstable angina. Therefore, plaque
      vulnerability has been important role in the pathogenesis of acute cardiovascular
      events. Recent studies have reported the mechanisms responsible for plaque
      rupture and erosion leading to acute thrombosis in the histologic, cellular, and
      molecular levels. A basic approach to atherosclerotic diseases is important and
      helpful for physicians in clinical situation. In this article, we review related
      factors leading to plaque rupture and erosion in the basic aspect.

PMID- 16613182
TI  - [Electrocardiographic diagnosis in patients with acute coronary syndrome].
AB  - Electrocardiographic role in a diagnosis of ischemic heart disease has still
      important value. As important electrocardiographic findings of myocardial
      ischemia, there are ST elevation or depression, increase high T wave (hyperacute
      T wave), negative T wave and negative U wave, but it is particularly important to
      compare those findings and manifestation. Because the patient can always carry
      it, event ECG is advantageous in that they can record electrocardiography by
      themselves when they have some symptom. It is necessary to have attention to what
      abnormal findings of the electrocardiogram which it is easy to be overlooked such
      as increase T wave or negative U wave appear in early stage of phase of acute
      coronary syndrome. When the patient has some symptom that acute coronary syndrome
      is thought about, it is necessary to record electrocardiograms on several times
      and to do follow up even if there is no electorcardiographic abnormalities at
      first recording.

PMID- 16613181
TI  - [Relation between gene polymorphism and acute coronary syndrome].
AB  - The acute coronary syndrome, consisting of myocardial infarction and unstable
      angina, is the most important manifestation of coronary disease and is
      characterized by atherosclerotic plaque disruption and coronary thrombosis. In
      the coronary vessel wall, this process contains abnormalities of extracellular
      matrix, fibrinolytic system, endothelial function, and, possibly, vascular
      inflammation. Potentially thousands of genes are relevant to this apparently
      complex disease. Although many risk factors are intercorrelated, raising the
      possibility of a higher level of genetic control by a small number of master
      genes that control fundamental physiological systems. Such genes are likely to be
      relevant to the combined processes of plaque instability and coronary thrombosis.

PMID- 16613183
TI  - [Coronary arteriography for diagnosis of acute coronary syndrome].
AB  - The acute coronary syndrome (ACS) is an acute ischemic attack resulted from
      disruption of coronary atheroma followed by thrombus formation. Because current
      guidelines recommend an early invasive strategy for patients who have ACS with
      and without ST-segment elevation and with an elevated cardiac troponin T level,
      early coronary angiography is indicated in almost all patients with ACS. Coronary
      angiography of ischemia related artery reveals total occlusion or severe stenosis
      associated with thrombus. In a patient with multivessel disease, a careful
      interpretation of coronary angiography is needed to identify the ischemia related
      artery.

PMID- 16613184
TI  - [CT, MRI for diagnosis of acute coronary syndrome].
AB  - Recent pathological and clinical observations support the notion that coronary
      artery plaque disruption and subsequent thrombosis is the primary cause of acute
      coronary syndrome (ACS) including acute myocardial infarction and unstable
      angina. Therefore, detection and characterization of coronary artery plaques are
      of utmost importance in the management of patients with suspected coronary artery
      disease. Histologic and clinical observations using intravascular ultrasound have
      suggested that vulnerable, rupture-prone plaques are characterized by the
      presence of large lipid cores, thin fibrous caps and positive coronary artery
      remodeling. In this review, we describe the efficacy of multislice computed
      tomography (MSCT) to characterize vulnerable plaques, especially in patients with
      suspected ACS. In addition, the efficacy of coronary magnetic resonance imaging
      is discussed.

PMID- 16613185
TI  - [Acute coronary syndrome diagnosed by the intravascular imaging].
AB  - Coronary plaque rupture and the following formed thrombus have been revealed the
      cause of acute coronary syndrome. This evidence had been proposed by the
      pathologists 100 years ago; however, the intravascular imaging such as
      intravascular ultrasound (IVUS) or coronary angioscopy has revealed the clinical
      evidences in live human being. Thrombus and yellow plaque detected by coronary
      angioscopy as well as the ruptured fibrous cap detected by IVUS are the
      characteristics for the lesion of ACS, which does not show the significant
      stenosis. Thus, ACS lesion should be diagnosed by IVUS or coronary angioscopy.

PMID- 16613186
TI  - [Multi-biomarker approach to acute coronary syndrome].
AB  - High-risk acute coronary syndrome is characterized by vulnerable-plaque with
      subocclusive thrombus and down-stream microemboli spreading minor myocardial
      damage, resulting in non-ST-elevation myocardial infarction. Advances in the
      understanding of the pathogenesis and consequences of acute coronary syndrome
      have stimulated development of novel biomarkers, and expanded their role in the
      different spectrum of the underlying pathophysiology, namely multi-biomarker
      strategy; consisted of biomarkers for 1) myocardial necrosis(membrane damage to
      myofibril necrosis), 2) plaque destabilization, 3) myocardial stress(ischemic
      stress per se and end-diastolic atrial or ventricular wall stress), 4) myocardial
      ischemia, and 5) inflammatory process. In this article, we review clinical
      importance of novel biomarkers referring our previous clinical investigation and
      other reports, especially troponin T for detection of minor myocardial damage
      associated with vulnerable plaque with thrombus/embolus, heart-type fatty acid 
      binding protein for earlier detection of myocardial damage and it's role for the
      rule-out triage, N-terminal pro-BNP for earlier risk stratification in cardiac
      emergency, and soluble CD40 ligand for earlier identification of plaque
      destabilization with platelet activation in non-ST-elevation acute coronary
      syndrome.

PMID- 16613187
TI  - [Fibrinolysis in patients with acute coronary syndrome].
AB  - The reperfusion therapy including both fibrinolytic therapy and primary
      percutaneous coronary intervention (PCI) has been established in patients with ST
      segment elevation acute myocardial infarction (STEMI). Fibrinolysis has the
      advantage of universal availability and short time to administration. Because the
      benefit of fibrinolysis is directly related to the time from symptom onset to
      treatment as demonstrated in many studies, every effort must be made to minimize
      any delays between symptom onset and the initiation of a safe and effective
      reperfusion strategy in patients with STEMI. Although the benefit of fibrinolysis
      is limited by inadequate reperfusion or reocclusion of the infarct-related artery
      in a sizable portion of patients, fibrinolysis followed by planned PCI can be one
      of approaches in patients presenting within 2 or 3 hours from onset of STEMI.

PMID- 16613188
TI  - [PCI for the patients with acute coronary syndrome].
AB  - Numerous clinical trials have been conducted to compare therapeutic efficacy of
      thrombolysis and that of primary percutaneous coronary intervention (PCI) in the
      patients with acute coronary syndrome (ACS). Several recent meta-analyses
      revealed that primary PCI provides better short-term and long-term clinical
      results for ACS patients than thrombolysis does. However, in order to obtain such
      benefit of primary-PCI, PCI procedure has to be done by the team of well-trained
      angioplasters and para-medical staffs with on-site surgical back-up, as indicated
      by the JCS guideline for ACS treatment.

PMID- 16613189
TI  - [Technical evolution of the stent].
AB  - Percutaneous coronary intervention has been hampered by restenosis since its
      inception. Many research projects including the use of various devices and
      systemic drug administration have shown disappointing results. Recently, the
      advent of drug-eluting stents has reduced incidence of restenosis compared with
      bare metal stents. This article provides an overview of the developments of drug
      eluting stents, their clinical impact on the treatment of acute coronary
      syndrome, and their future perspectives.

PMID- 16613190
TI  - [Thrombus aspiration therapy for acute coronary syndrome].
AB  - Reducing thrombus burden before percutaneous coronary intervention (PCI) may lead
      to better myocardial reperfusion in patients with acute myocardial infarction
      (AMI). Thus, several types of devices have been developed to remove intracoronary
      thrombus during reperfusion therapy, which includes X-sizer, AngioJet, and
      aspiration devices. There are two important randomized studies by using X-sizer
      and AngioJet to evaluate the efficacy of thrombus removal, which implied the
      possible benefit in myocardial tissue reperfusion, but could not prove the
      beneficial impact on clinical outcomes. As for thrombus aspiration, there also
      seems to be no data to demonstrate its clinical impact on prognosis. However, the
      aspiration therapy has been accepted widespread in Japan, mainly because of the
      practical benefit to clarify the lesion morphology with easy manipulation.
      Further studies are needed to demonstrate the characteristics of patient or
      lesion characteristics which are likely to benefit most by thrombus removal
      therapy or which demand to perform distal protection strategy.

PMID- 16613191
TI  - [Strategy for cardiac arrhythmias in acute coronary syndrome].
AB  - Acute coronary syndrome causes several types of arrhythmia because of its
      electrical instability and ischemia. The most important arrhythmia is ventricular
      tachycardia which degenerates to ventricular fibrillation. Prompt direct current
      cardioversion will be needed and prevention of ventricular tachyarrhythmia by
      potassium channel blocker became more popular in Japan. Nifekalant or amiodarone
      should be selected. Atrial fibrillation also occurred in the patients with acute
      coronary syndrome, and it may deteriorate hemodynamics condition. Therefore,
      termination and prevention of atrial fibrillation is another important issue in
      acute coronary syndrome. Aprindine, amiodarone, or bepridil will be the choice to
      prevent recurrent atrial fibrillation after direct current cardioversion.

PMID- 16613192
TI  - [Use of angiotensin converting enzyme inhibitors and angiotensin receptor
      blockers in patients with acute coronary syndrome].
AB  - Renin-angiotensin system is well known that it plays an important role in the
      initiation and amplification of atherosclerosis that lead to cardiovascular
      disease. Angiotensin II is deeply involved in vasoconstriction, oxidative stress,
      inflammation, thrombosis, vascular remodeling, and sympathetic nerve activity.
      Many studies have documented the favorable effects of angiotensin converting
      enzyme inhibitor(ACE-I) and angiotensin receptor blocker(ARB) on cardiovascular
      disease in basic and clinical trials. Now accumulated evidences suggest ACE-I and
      ARB potentially prevent coronary plaque rapture, thrombosis and myocardial
      remodeling with acute coronary syndrome (ACS). ACS is occurred from plaque
      rupture on mild to moderate coronary atherosclerosis. Therefore, on treatment of
      ACS, it is important to prevent the plaque rupture and thrombosis by
      pharmacological intervention with ACE-I and ARB than coronary artery intervention
      which is down stream therapy for coronary artery stenosis.

PMID- 16613193
TI  - [Anti-platelet drugs (aspirin, ticlopidine, etc)].
AB  - Previous clinical trials have shown that anti-platelet drugs, such as aspirin and
      ticlopidine, are approved for prevention of serious cardiovascular events in
      special populations who are at increased risk of cardiovascular events. Of these
      trials, the Antithrombotic Trialists' Collaboration (ATT) meta-analysis includes
      approximately 200,000 patients: Anti-platelet therapy was associated with a 34%
      reduction in the risk of nonfatal myocardial infarction, a 25% reduction in the
      risk of stroke, and a 15% reduction in the risk of vascular death. Also in
      patients with acute coronary syndrome (acute myocardial infarction and unstable
      angina), both aspirin and ticlopidine have been shown to prevent serious
      cardiovascular events.

PMID- 16613194
TI  - [Anti-anginal medication in management of acute coronary syndrome].
AB  - Pharmacological therapy for acute coronary syndrome (ACS) is divided into the
      treatment for myocardial ischemia and that for coronary thrombosis. Immediate
      nitrates(sublingual tablets and sprays) are used to alleviate attacks and
      patients not responding them are treated by intravenously in 24 hours. The
      initial treatment for non-ST-segment elevation myocardial infarction(NSTEMI) with
      the administration of nitrates and beta blocker is judged as Class I (evidence
      level B) by ACC/AHA classification. Administering beta blocker in patients with
      ACS has reduced the progression to myocardial infarction by 13%. Ca antagonist is
      administered in patients for whom nitrates and/or beta blocker are
      contraindicated or in whom myocardial ischemia persists or frequently relapses in
      spite of the treatment with an adequate dose of the drugs. Since recent studies
      have suggested that ACS may not result from a local vascular stenosis, but from
      coronary inflammation, treating the local vascular lesion alone with PCI is not
      enough. Rather, pharmacological therapy is important to reduce overall patient
      risk, thereby suppressing the progress of atherosclerosis.

PMID- 16613195
TI  - [Statin treatment in patients with acute coronary syndrome].
AB  - In PROVE IT trial, intensive lipid-lowering therapy with statin (80 mg of
      atorvastatin daily) provides greater protection against cardiovascular events
      than does a standard regimen (40 mg of pravastatin daily) in patients with acute
      coronary syndrome (ACS), indicating that such patients benefit from early and
      continued lowering of LDL cholesterol to levels substantially below current
      target levels. However, differences between Japanese and Westerns as far as
      atherogenesis and response to statins are concerned, remain an unsolved problem
      that requires additional investigation. New guideline for the management of
      patients with ACS is needed for Japanese patients.

PMID- 16613196
TI  - [Therapeutic angiogenesis for ischemic diseases].
AB  - The clinical consequences of peripheral arterial disease include pain on walking,
      pain at rest and loss of tissue integrity in the distal ischemic limbs. Although
      development of beneficial drugs and intervention devices do contribute to the
      treatment of this disease, critical limb ischemia is estimated to develop in 500
      to 1,000 individuals per million per year. As angiogenic growth factors can
      stimulate the development of collateral arteries, a concept called "therapeutic
      angiogenesis" is now evaluated in the clinical fields. Recent progress in
      molecular biology has led to the development of gene therapy as a new strategy to
      treat a variety of cardiovascular diseases using angiogenic growth factors such
      as vascular endothelial growth factor (VEGF). Therapeutic angiogenesis using
      angiogenic growth factors is expected to be a new treatment for patients with
      severe ischemic heart or peripheral arterial disease.

PMID- 16613197
TI  - [Emergency/resuscitation systems and problems].
AB  - The proportion of cardiac etiology is more than 50% of the patients of out-of
      hospital cardiac arrest and the cause of cardiac etiology is acute coronary
      syndromes (ACS) in about 70%. Although the mortality rate of acute myocardial
      infarction with ST elevation was about 7% in the cardiac reperfusion era, there
      is a high mortality rate in the patients with ACS who developed out-of-hospital
      cardiac arrest. We summarized the emergency medical service system in Japan and
      its problems. Achieving the optimal survival rate for out-of-hospital cardiac
      arrest due to ACS is the challenge now and in the future.

PMID- 16613198
TI  - [Acute coronary syndrome risk management].
AB  - Coronary atherosclerosis begins in early life and progresses through adulthood,
      exacerbated by various risk factors. The past decade has witnessed an increasing
      recognition that endothelial dysfunction and inflammatory mechanisms play a
      central role in the pathogenesis of atherosclerosis and acute coronary syndrome
      (ACS). Advances in the management of patients with ACS have evolved dramatically.
      Recently the concept of interventional cardiology expand beyond mechanical
      revascularization to embrace preventive interventions that forestall future
      cardiac and vascular events. The pleiotropic effect of preventive agents
      contributes to early and significant risk reduction in high-risk patients and
      also after being suffered from ACS.

PMID- 16613199
TI  - [Complications related to procedures for acute coronary syndrome].
AB  - Recent advances in thrombolytic therapy and percutaneous coronary intervention
      (PCI) have resulted in dramatic improvements in the outcome of patients with
      acute coronary syndromes (ACS). Unfortunately, the reduced risk of cardiac and
      non-cardiac complications associated with advancements in technology has also
      been paralleled by an increase in the incidence of some complications. The most
      important complications relate to abrupt vessel closure with PCI, which may
      result in myocardial infarction or cardiac death. Major bleeding is also a
      relatively frequent non-cardiac complication of thrombolytic therapy and it is
      associated with a poor hospital prognosis. Most complication can be prevented or
      at least minimized with proper strategy, execution, and patient selection.

PMID- 16613200
TI  - [Obesity in offspring with maternal undernutrition during pregnancy].
AB  - Recent epidemiology demonstrates higher rate of obesity and metabolic syndrome in
      offspring with undernutrition in utero. IUGR babies with intrauterine
      undernutrition grow rapidly to catch up with normal growth course. Leptin is an
      adipocyte derived satiety factor that regulates food intake and energy
      expenditure. We demonstrated in mice model with maternal food restriction during
      pregnancy that premature leptin surge during neonatal catch up growth of the
      offspring lead them to impaired leptin sensitivity and obesity in adulthood.

PMID- 16613201
TI  - [Renin-angiotensin system in atherosclerosis].
AB  - The renin-angiotensin system(RAS) has been demonstrated to play a critical role
      in initiation and progression of atherosclerosis, thereby contributing to
      development cardiovascular diseases. Angiotensin II(Ang II), major substrate in
      RAS, stimulates atherosclerosis through various processes such as endothelial
      dysfunction, cellular proliferation and inflammation. Recently, local RAS in
      vasculature is reported to play an important role. Many of these atherogenic
      effects of Ang II are mediated by reactive oxygen species(ROS). Investigation of
      the role of ROS and inflammation induced by RAS may provide a clue to
      understanding the pathophysiology of atherosclerotic diseases, and may lead to a
      new therapeutic strategy.

PMID- 16613202
TI  - [Working conditions for surgeons: consideration of flexible working hours system
      in national university corporation].

PMID- 16613203
TI  - [Current status of endoscopic surgery for malignancies].

PMID- 16613204
TI  - [Current topics of endoscopic surgery for thyroid cancer].
AB  - Endoscopic surgery has been introduced in the field of thyroid disease.
      Endoscopic thyroid surgery is divided into complete endoscopic surgery using CO2
      gas, which is approached from the axilla, mammary areola, and anterior chest; and
      video-assisted thyroid surgery without CO2 gas, approached from the neck or
      anterior chest under the clavicula through a small incision. Many thyroid tumors
      are benign, and cases of thyroid cancer are few. Only 7.9% of patients who
      underwent endoscopic thyroid surgery in the English and Japanese literature had
      papillary thyroid cancer. Most of these underwent video-assisted thyroidectomy
      without gas. The indications for endoscopic surgery in papillary thyroid cancer
      is microcancer or small tumor without lympnode metastasis before surgery. In
      follicular thyroid cancer, minimally invasive thyroid cancer of less than 5cm is
      recommended for endoscopic thyroid surgery. Furthermore, in medullary carcinoma
      with multiple endocrine neoplasia, prophylactic thyroidectomy can be performed
      using these endoscopic techniques. At present, it is still controversial whether
      endoscopic surgery should be performed to treat thyroid cancer.

PMID- 16613205
TI  - [Endoscopic breast surgery for breast cancer].
AB  - Since 1995, endoscopic breast surgery (EBS) has been gradually established in
      Japan. Establishment of EBS was inextricably linked to explosive development of
      instruments for endoscopic surgery and profound theoretical understanding, how to
      perform broad & stable dissection of the compact connective tissue thorough small
      incisions. EBS consisted chiefly of two procedures added to breast and axilla and
      procedures to breast is classified into three methods according to incisions,
      axillar, periareolar and combined incisions. With EBS technique, any kind breast
      surgery, sentinel node biopsy, reconstruction, augmentation, and benign tumor
      excision, could be performed through same skin incisions. Curability of breast
      cancer EBS is same as that with conventional method and local recurrence rate
      after total and partial mastectomy. All breast cancer without skin involvement of
      cancer would be candidate for EBS. To minimize invasiveness of treatment and
      maintain cosmetic outcome of breast, combination treatment of ablation treatment,
      EBS and evolution of radiation therapy would be important.

PMID- 16613206
TI  - [Video-assisted thoracoscopic surgery for lung cancer: current indications].
AB  - Recently, video-assisted thoracoscopic surgery (VATS) has been widely applied in
      lung cancer surgery in Japan, although there is no consensus on the definition of
      VATS and its standard techniques. VATS lobectomy may result in long-term survival
      rates as high as after standard thoracotomy and is becoming an optional treatment
      for stage IA lung cancer. It is still not a standard treatment because of the
      problems of safety and oncologic radicality. However, as long as the safety and
      radicality are ensured by the tumor type, patient risk factors, and the expertise
      of the surgeon, less-invasive techniques like VATS should be performed.

PMID- 16613207
TI  - [Current status and evaluation of thoracoscopic esophagectomy for thoracic
      esophageal cancer].
AB  - The current status and evaluation of esophagectomy by thoracoscopic approach for
      thoracic esophageal cancer are described. The esophagectomy by thoracoscopic
      approach for thoracic esophageal cancer have been reported in some Instituts
      since 1996 in Japan. In 10 years, series consisting a large number of esophageal
      cancer patients have been treated with esophagectomy by thoracoscopic approach
      and evaluated about operative safety, curabirity and postoperative morbidity.
      Now, the establishment of training system is the most important subject to
      achieve the standardization of thoracoscopic esophagectomy for thoracic
      esophageal caner.

PMID- 16613208
TI  - [Current status and evaluation of laparoscopic surgery for gastric cancer].
AB  - Laparoscopic surgery for gastric cancer in Japan has been established as a
      treatment for early gastric cancer after technical improvements, development of
      instruments, and efforts of surgeons. The technigue was extended to some advanced
      gastric cancers and now plays an important role in the gastric cancer treatment
      strategy with open surgery and endoscopic mucosal resection. Laparoscopic surgery
      for early gastric cancer has been evaluated as less invasive, offering radical
      cure, and safe in several clinical trials and case-control studies. However, the
      accumulation of more cases and additional basic research are necessary before
      adapting laparoscopic surgery for advanced gastric cancer. A large-scale,
      randomized, controlled study will be carried out in early gastric cancer, and, as
      a result, scientific and objective evaluation of laparoscopic surgery for gastric
      cancer will be possible in the near future.

PMID- 16613209
TI  - [Laparoscopic surgery for colonic cancer: present status and evaluation].
AB  - It has been 15 years since laparoscopic surgery was first performed in colonic
      cancer. An inquiry-based analysis by the Japan Society of Endoscopic Surgery
      (JSES) in 2003 showed a steady increase in the number of laparoscopic colonic
      resections for cancer. This report also indicates that advanced cancer candidates
      exceeded early-stage patients in 2003. From the technical point of view, pure
      laparoscopic access and a medial dissection approach rather than hand-assisted
      laparoscopic surgery (HALS) and a lateral dissection approach is more likely to
      be selected as a standard procedure. In 2004, the Endoscopic Surgical Skill
      Qualification System was proposed by the JSES to promote safer laparoscopic
      surgery in Japan. For colonic qualification, a thorough videotape of colonic
      cancer resection is to be evaluated so that not only laparoscopic surgical skill
      but also oncologic handling is taken into account. In clinical research, based on
      the results of a multicenter, randomized, controlled study of open vs.
      laparoscopic-assisted colectomy in the USA and Europe, a Japanese trial has also
      now started to determine the optimum quality control of surgical skill. The
      results of this study arre expected to lead to less deviation in the level of
      surgical skill.

PMID- 16613210
TI  - [Clinical islet transplantation].

PMID- 16613211
TI  - [What we can learn from a case of medical malpractice].

PMID- 16613212
TI  - [Laparoscopic adrenalectomy].

PMID- 16613213
TI  - [Study of thrombophilia in Japan achieved by the Department of Clinical Chemistry
      and Laboratory Medicine, Kyushu University].

PMID- 16613214
TI  - [Regulation of mitochondrial biogenesis and morphogenesis].

PMID- 16613215
TI  - Effect of probucol on elderly hypercholesterolemic patients in the FAST study.
AB  - The present study involved a detailed post hoc comparison of the efficacy and
      safety of lipid-lowering therapy in elderly hypercholesterolemic patients from
      the Fukuoka Atherosclerosis Trial (FAST). The FAST cohort of 246
      hypercholesterolemic patients included 76 patients who were (75 years old.
      Patients were randomized to receive probucol (500 mg/day) or pravastatin (10
      mg/day) therapy, or to a control group (diet alone), and then were followed for 2
      years. In patients > or = 75 years old, either probucol or pravastatin achieved a
      significant reduction of carotid intima-media thickness (IMT). In patients <75
      years old, lipid-lowering therapy also achieved a significant reduction of IMT.
      In patients > or = 75 years old receiving probucol, the relative risk (95%
      confidence interval) of all-cause mortality was 0.15 (0.02 to 1.28) and that for
      major coronary events was 0.12 (0.02 to 1.04). In conclusion, probucol reduced
      the incidence of cardiovascular disease in elderly hypercholesterolemic patients
      as well as younger patients.

PMID- 16613216
TI  - [Treatment strategy for dural arteriovenous fistulae].

PMID- 16613217
TI  - [Uchimura artery (arteries)].

PMID- 16613218
TI  - [Radiosurgery of epidermoid tumors with gamma knife: possiblility of
      radiosurgical nerve decompression].
AB  - Long-term results of radiosurgery for epidermoid tumors are reported. There are 7
      cases including 2 males and 5 females, ages ranging from 6 to 46 (mean: 33.3
      years). At radiosurgery whole tumor was covered in 4 cases and partially covered
      in 3 cases in attempting to relieve cranial nerve signs like trigeminal neuralgia
      and facial spasm. The mean maximum and marginal doses were 25.6 Gy and 14.6 Gy
      respectively. In the mean follow-up of 52.7 months, all the tumors showed good
      tumor control without any progression and tumor shrinkage has been confirmed in 2
      out of the 7 cases. Symptomatic trigeminal neuralgia improved or disappeared in
      all 4 cases and facial spasm disappeared in one. No neurological deterioration
      was found in any of the cases after the treatment. In conclusion, it is apparent
      that epidermoid tumors do respond well to radiosurgery and the accompanying
      hyperactive dysfunction of cranial nerves is significantly improved by gamma
      knife treatment with either entire or partial tumor coverage. Therefore the
      radiosurgical nerve decompression for epidermoid tumor seems to be achieved by
      gamma-radiosurgery.

PMID- 16613219
TI  - [Aneurysms at the early branch of middle cerebral artery].
AB  - The cortical arteries arising from the proximal (Ml) segment of the middle
      cerebral artery (MCA) are called "early branches". We retrospectively analyzed
      clinical features in 10 patients with aneurysms located at the early branches of
      MCA. The incidence of these aneurysms was 9.5% among 95 MCA aneurysms. Patients
      consisted of 4 males and 6 females. Ages were 33-77 years old (average of 54.4).
      Four patients presented with subarachnoid hemorrhage (2 of them had intracerebral
      hematoma). The aneurysms were classified into 2 groups, the group of the early
      frontal branch (EFB: 7 cases) and the early temporal branch (ETB: 3 cases). All
      aneurysms were smaller than 6mm in diameter. The surgical treatment was performed
      through the pterional approach. Poor outcome occurred in 3 ruptured aneurysms of
      EFB (MD 1, SD 1, and D 1). At surgery, it is necessary to produce the working
      space by dissecting sylvian fissure sufficiently and to prevent ischemic
      complication by avoiding injury of the lenticulostriate arteries (LSA).

PMID- 16613220
TI  - [Case of hydrocephalus associated with vestibular schwannoma, treated by tumor
      removal].
AB  - A 57-year-old male presented with gait disturbance, urinary incontinence,
      dementia resembling symptom of normal pressure hydrocephalus (NPH) and was
      admitted to our institusion. A computerized tomographic scan (CT) and magnetic
      resonance imaging (MRI) revealed hydrocephalus as well as a tumor in the right
      cerebellopontine angle. We diagnosed communicating-type hydrocephalus associated
      with the vestibular schwannoma and tumor removal was performed prior to
      ventriculo-peritoneal (V-P) shunt. After surgery, symptoms of the patient
      disappeared promptly and cerebrospinal fluid protein elevation was normalized.
      One month after surgery, CT and MRI revealed reduction of the ventricle size and
      V-P shunt became unnecessary. Hydrocephalus is occasionally complicated by
      vestibular schwannoma. The majority results from obstruction of the cerebrospinal
      fluid (CSF) pathway by large tumors. But, small tumors also cause communicating
      type hydrocephalus. Although the selection of the treatment is controversial,
      tumor removal without a shunt is considered as a good strategy for management of
      hydrocephalus associated with vestibular schwannoma.

PMID- 16613221
TI  - [Hemifacial spasm due to vascular compression of the distal portion of root exit
      zone of the facial nerve: report of two cases].
AB  - It has been generally assumed that only vascular contact at the root exit zone
      (REZ) of the facial nerve can cause hemifacial spasm. We treated two cases of
      hemifacial spasm in which compression of the distal site of the REZ of the facial
      nerve produced symptoms. The microvascular decompression for the patients showed
      excellent results. Extreme care must be taken not to stretch the internal
      auditory artery during surgical manipulation. The ABR monitoring is useful to
      prevent the postoperative hearing loss. It must be kept in mind that the
      compression of distal portions of the facial nerve may be responsible for
      hemifacial spasm in cases in which neurovascular compression at the REZ is not
      confirmed intraoperatively.

PMID- 16613222
TI  - [Repeated, reversible MR angiographic findings in pediatric moyamoya disease:
      case report].
AB  - The authors report a 6-year-old girl presented with headache and transient
      ischemic attack due to moyamoya disease. MR angiography (MRA) revealed that her
      symptoms were closely related to reversible deterioration of stenosis in the left
      middle cerebral artery (MCA). Deterioration of stenosis led to a decreased flow
      signal in the distal branches of the left MCA. MRA could also detect reversible
      stenotic changes in the right MCA, although she did not develop any neurological
      symptom. Although precise mechanism of reversible MR angiographic findings is
      still unknown, the phenomenon may play an important role in disease progression
      in pediatric patients with moyamoya disease.

PMID- 16613223
TI  - [Leiomyosarcoma of the uterus metastatic to the brain].
AB  - A case of 52-year-old female presented with dysarthria and paresis of right upper
      extremity 3 years after an operation and chemotherapy for uterine leiomyosarcoma.
      Magnetic resonance imaging showed an enhanced mass in the left corona radiata.
      Brain biopsy was carried out and pathological examination of the specimen showed
      features of a leiomyosarcoma. Uterine leiomyosarcoma is an uncommon tumor and its
      metastasis to the brain is rare. Only 13 other cases have been published. The
      patient underwent gamma-knife therapy and obtains good quality of life.

PMID- 16613224
TI  - [Endovascular treatment of large petrous internal carotid artery aneurysm
      associated with chronic otitis media: case report].
AB  - Aneurysms of the petrous internal carotid artery are rare, and surgical treatment
      of the aneurysm in the petrous bone carries high risk with procedure. We report a
      case of large petrous internal carotid artery aneurysm associated with otitis
      media. A 58-year-old female was admitted to our institution with left hearing
      loss and facial palsy. She had 4-year history of left exudative otitis media.
      Imaging studies demonstrated a 17 mm left petrous internal carotid artery
      aneurysm, destroying osseous partition between carotid canal and Eustachian tube,
      and protruding into left middle cranial fossa. Endosaccular coil embolization
      with balloon assist technique was performed successfully without neurological
      deficit. Follow up magnetic resonance angiogram demonstrated complete
      obliteration of the aneurysm without parent artery occlusion. Traumatic, mycotic,
      radiation, and congenital origin have been implicated for petrous internal
      carotid artery aneurysm. In a review of the literature, 11 cases of mycotic
      aneurysms in this location were reported and all of them were complicated with
      chronic otitis media. Because of its close proximity of middle ear and Eustachian
      tube, adventitial infection of the artery weakens the arterial wall, and gives
      rise to formation of aneurysm. We conclude that our case is of mycotic origin,
      and endosaccular coil embolization is effective and less invasive treatment.

PMID- 16613225
TI  - [Case of clipping of a ruptured aneurysm of the posterior cerebral artery (P2)
      via the transchoroidal-fissure approach].
AB  - A 59-year-old female was found to be drawn in a swimming pool and transferred to
      our hospital. The patient was comatose on admission (Hunt & Kosnk: Grade IV).
      Computed tomography (CT) showed diffuse subarachnoid hemorrhage (SAH) with thick
      hematoma in the left ambient cistern. Conventional cerebral angiography and 3D
      digital subtraction angiography revealed aneurysms (ANs) of the left posterior
      cerebral artery (P2), and bifurcation of the left internal carotid and posterior
      communicating arteries (IC-PC). Successful neck clipping was performed the same
      day through the temporal horn via the insula for ruptured P2 AN, and the non
      ruptured IC-PC AN was also obliterated using a pterional approach. Postoperative
      course was uneventful except for initial disturbance of consciousness and
      aphasia. The patient was discharged with no neurological deficit 1 month after
      surgery. This approach may be preferable in cases involving high positioned PCA
      AN in the ambient cistern, particularly in the acute phase of severe SAH, as the
      brain is protected from the detrimental effects of strong temporal retraction and
      a wider working space is provided.

PMID- 16613226
TI  - Surgical revascularization for acute coronary syndrome: comparative surgical and
      long-term results.
AB  - OBJECTIVE: The purpose of this study was to evaluate the adequate timing of
      coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS).
      METHODS: In our institution, emergency CABG has been avoided when possible for
      ACS patients favoring stabilization with medical therapies, including intra
      aortic balloon pumping or percutaneous coronary intervention. After thorough
      preoperative examinations, an urgent CABG is performed. A total of 67 patients
      with ACS underwent CABG, comprised of 33 patients receiving an emergency CABG
      (emergent group: E-G) and 34 patients receiving an urgent CABG (urgent group: U
      G). The early and long-term results were evaluated retrospectively. RESULTS:
      Preoperatively, the incidences of acute myocardial infarction and cardiogenic
      shock were significantly higher in E-G. No significant differences were found in
      the intraoperative factors except for the number of distal anastomoses (2.5 in E
      G vs. 3.1 in U-G, p=0.01). The hospital mortality was 9.1% in E-G, and 2.9% in U
      G, with no significant difference between the groups. Moreover, no patient in U-G
      necessitated emergency CABG while waiting for surgery. The patency rate of the
      grafts was 100% in E-G, and 96.2% in U-G. The 5-year survival rate excluding in
      hospital death was 80.3% in E-G, and 78% in U-G (p>0.05). The 5-year cardiac
      event-free rate was 80.3% in E-G, and 80.9% in U-G (p>0.05). CONCLUSION: An
      emergency CABG can be reserved for ACS patients when symptoms and hemodynamic
      state are stabilized with medical therapies. Improvements in long-term results
      can be expected after high quality and complete surgical revascularization.

PMID- 16613227
TI  - Impact of mediastinal lymph node dissection on octogenarians with non-small cell
      lung cancer.
AB  - OBJECTIVE: Impacts of mediastinal lymph node dissection on a patient's course
      after pulmonary resection is unclear in octogenarians with non-small cell lung
      cancer. METHODS: Retrospectively identified subjects included 39 octogenarians
      and 1 nonagenarian, with grades according to the Charlson Comorbidity Index
      ranging from only 0 to 2. We performed mediastinal lymph node dissection in 19
      patients (D group), and just lymph node sampling biopsy in the other 21 (S
      group). We compared clinicopathologic features and outcome after surgery between
      both groups. RESULTS: Deterioration of performance status at the time of
      discharge, evident in 17 patients overall, was significantly more frequent in the
      D group. Postoperative complications occurred in 27 patients overall and there
      was no significant difference between the two groups. Survival rates in younger
      patients at 1, 3, and 5 years were 86, 59, and 49%, respectively; in
      octogenarians these were 83, 58, and 42% (no significant difference). Nor did
      survival differ significantly by surgical management of mediastinal lymph nodes;
      1-, 3-, and 5-year survival rates were 94, 63, and 40%, respectively in the D
      group and 78, 66, and 43%, respectively in the S group. CONCLUSION: Octogenarians
      with non-small cell lung cancer should be treated by urgent pulmonary resection
      whenever possible. Since mediastinal lymph node dissection has little effect on
      long-term survival or the carried risk of worsening performance status at
      discharge, pulmonary resection without complete mediastinal lymph node dissection
      should be considered.

PMID- 16613228
TI  - Preoperative chemotherapy for cStage III-pN0 patients with non-small cell lung
      cancer.
AB  - OBJECTIVES: Survival benefits with preoperative chemotherapy for non-small cell
      lung cancer (NSCLC) remain controversial. Preoperative chemotherapy may act on
      micrometastasis but not lymph node metastasis. To clarify the role of induction
      chemotherapy for control of micrometastasis, we reviewed and compared 5-year
      follow-ups of clinical stage III but pathologically-proven node-negative NSCLC
      patients after complete resection with or without preoperative chemotherapy.
      METHODS: We reviewed 148 consecutive patients who underwent anatomical lung
      resection and mediastinal nodal dissection for pathologically-proven node
      negative NSCLC at our hospital between 1994 and 1999. Fifty-six patients were
      preoperatively diagnosed as stage III: 26 received platinum-based chemotherapy
      prior to surgery (PCT group) and 30 underwent surgery without any prior
      chemotherapy (PRS group). RESULTS: The 5-year survival rate for clinical stage
      I/II and pathological node-negative patients was 74.9%; for clinical stage III,
      but for pathological node-negative patients it was 92.3% in the PCT and 63.3% in
      the PRS groups. The survival benefit of preoperative chemotherapy was significant
      for clinical stage II patients without node involvement. CONCLUSION: Preoperative
      chemotherapy may provide survival benefits for node-negative NSCLC patients.

PMID- 16613229
TI  - Arterial switch operation using aortic homograft for transposition of the great
      arteries with pulmonary regurgitation.
AB  - We report a case of a 15 month-old boy who underwent the arterial switch
      operation using cryopreserved aortic homograft for transposition of the great
      arteries with pulmonary regurgitation, with coexisting right ventricular outflow
      tract obstruction precluding atrial switch operation. Follow-up echocardiography
      at 6 months showed trivial neoaortic valve regurgitation, no significant systemic
      outflow obstruction, with good cardiac function. In small children, the choice of
      material for left ventricular outflow tract reconstruction is one of the most
      crucial issues. Cryopreserved homograft has been one of the primary options for
      the aortic valve replacement in small children because of the ease of suturing
      and excellent hemostasis.

PMID- 16613230
TI  - Pulmonary sequestration with high levels of tumor markers tending to be
      misdiagnosed as lung cancer.
AB  - A 62-year-old man with hemoptysis and an abnormal shadow on chest roentgenogram
      was diagnosed as having anomalous systemic arterial supply to the normal basal
      segment of the left lower lobe. The preoperative serum carbohydrate antigen 19-9
      and carcinoembryonic antigen levels were 73.8 units/ml and 10.8 ng/ml,
      respectively. Histopathological examination confirmed that the lesion was an
      intralobar pulmonary sequestration without air connection. There was no malignant
      finding in the resected specimen. The serum values of tumor markers returned to
      their approximate normal ranges after lower lobectomy.

PMID- 16613231
TI  - Aortic dissection late after aortic valve replacement.
AB  - We experienced 3 cases of an aortic dissection occurring late after an aortic
      valve replacement, and successfully treated by an aortic root replacement. An
      aortic dissection involving the ascending aorta can develop late after an aortic
      valve replacement, and such an occurrence is associated with a high mortality and
      morbidity. The development of effective surgical strategies at the initial aortic
      valve surgery, strict control of blood pressure after aortic valve replacement,
      serial evaluations of aortic size, and the prophylactic replacement of the
      ascending aorta for patients with aortic dilatation after aortic valve
      replacement, all play clinically important roles in preventing an aortic
      dissection after aortic valve replacement. When an aortic dissection occurs in
      patients with a previous aortic valve replacement, an aortic root replacement
      should be performed in order to avoid leaving the fragile diseased aortic wall
      including the sinus of Valsalva.

PMID- 16613232
TI  - Complete rupture of the posterior papillary muscle caused by late reperfusion for
      acute myocardial infarction.
AB  - We describe a patient with acute mitral regurgitation due to complete rupture of
      the papillary muscle immediately after successful late reperfusion for inferior
      myocardial infarction. An 81-year-old woman was admitted complaining of mild
      chest discomfort. Although the electrocardiograms, biochemical test results, and
      her clinical history showed that several days had passed since the onset of acute
      myocardial infarction, a late coronary stenting was performed. Immediately after
      successful stenting, she suddenly developed acute pulmonary edema, leading to
      cardiogenic shock. In addition to high pulmonary capillary wedge pressure (mean
      35 mmHg), color Doppler imaging revealed massive mitral regurgitation caused by
      complete rupture of the posterior papillary muscle. Emergent mitral valve
      replacement with a prosthetic valve was performed, saving the patient. Hence,
      late reperfusion should be considered carefully when treating a patient with a
      high risk, such as an elderly patient or a patient with single-vessel disease or
      initial transmural myocardial infarction.

PMID- 16613233
TI  - Successfully treated infected left ventricular pseudoaneurysm after the Dor
      operation.
AB  - A 65-year-old woman received a bovine pericardial patch repair with a sutureless
      technique for a left ventricular free-wall rupture. Three months later the Dor
      operation was performed for a left ventricular aneurysm. She was admitted again
      with a mycotic aneurysm 15 months after the Dor operation. Computed tomography
      suggested a rupture of the pseudoaneurysm due to a damaged endoventricular patch.
      An emergency Dor reoperation was performed with profound hypothermia. Right
      thoracotomy was performed with insertion of a left vent catheter via the right
      upper pulmonary vein in order to prevent ventricular distention. Omentopexy was
      performed to avoid infection of the mediastinum. The patient had an uneventful
      postoperative course.

PMID- 16613234
TI  - Metastatic chest wall tumor suspected to be of lung origin by immunoreactivity
      for cytokeratin 7 and 20.
AB  - We report a rare case of unknown primary carcinoma. A 36-year-old man was
      admitted to the hospital because of a chest wall tumor. Serum carcinoembryonic
      antigen level was 160 ng/ml. The resected chest wall tumor was pathologically
      diagnosed as metastatic adenocarcinoma, showing positive immunoreactivity for
      cytokeratin 7 and negative immunoreactivity for cytokeratin 20, suggesting lung
      origin. Serum carcinoembryonic antigen level returned to normal limits. Twenty
      one months later, a chest X-ray showed a nodular lesion in the left upper lobe
      and serum carcinoembryonic antigen level increased to 12.3 ng/ml. Left upper
      lobectomy was performed 23 months after chest wall resection. The resected tumor
      was pathologically diagnosed as primary lung adenocarcinoma, showing the same
      immunoreactivity as in the chest wall tumor. The combination of
      immunohistochemistry for cytokeratin 7 and 20 appeared to be a useful tool in
      determining the site of origin and helpful for premortem diagnosis of the origin
      of unknown primary carcinoma.

PMID- 16613235
TI  - Ruptured giant aneurysm of the ascending aorta caused by chronic aortic
      dissection.
AB  - A 55-year-old man developed acute chest pain and dyspnea. Computed tomography
      demonstrated a rupture of a giant aneurysm of the ascending aorta. The lesion was
      14 cm in diameter--the largest ever reported-and resulted from chronic aortic
      dissection. The patient did not have aortic insufficiency or aortic dissection
      around the coronary ostium. Graft replacement of the ascending aorta was
      performed successfully under deep hypothermia with right hemisphere perfusion.

PMID- 16613236
TI  - [Alpha-2-agonists: everyday anesthetic treatment in veterinary medicine, but far
      from safe. The consequences of accidental self injection].

PMID- 16613237
TI  - [Spread of post-weaning multisystemic wasting disease (PMWS) in Europe].

PMID- 16613238
TI  - [Pasture access and animal housing of the dairy cow in the Netherlands].

PMID- 16613239
TI  - [Avian influenza: the European legislation encourages a pandemic in humans and
      animals].

PMID- 16613240
TI  - [The market parties determine the quality standards. Interview by Miel Bingen].

PMID- 16613241
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. The last milk can].

PMID- 16613242
TI  - [(Ab)use of veterinary medicines in developing countries].

PMID- 16613243
TI  - [ONCOlogic Congress 2006. Head and neck tumors in dogs and cats].

PMID- 16613244
TI  - [Decision of the court of December 15th, 2005 (case 02/05)].

PMID- 16613245
TI  - [Relief for surviving relatives following a suicide].
AB  - After the suicide of a 43-year-old woman with known depression, a 41-year-old
      paraplegic man who recently developed diarrhoea and a 41-year-old woman with
      probable depression with symptoms of psychosis, the general practitioners of the
      surviving relatives offered a sympathetic ear, answered questions and prescribed
      sedatives and/or follow-up counselling. Completed suicide occurs 1500 times each
      year in the Netherlands and is strongly associated with psychiatric morbidity as
      well as psychological features like hopelessness and inability to solve problems.
      Generally, this irreversible act ofdespair can lead to existential difficulties
      in surviving relatives. Following a loss, acceptance of reality is essential to
      initiating effective emotional processing. The general practitioner is often
      first and foremost involved in providing support and comfort to bereaved
      families, during which many questions about the cause of death are brought up.
      The general practitioner helps the family to reconstruct the rationale behind the
      suicide in order to initiate effective emotional processing. In addition, the
      general practitioner can assess the risk of psychiatric morbidity, including
      suicidal behaviour, in surviving relatives.

PMID- 16613246
TI  - [New evidence for endovascular versus open treatment of patients with an aneurysm
      of the abdominal aorta].
AB  - Recent randomised trials have compared conventional and endovascular repair of
      asymptomatic abdominal aortic aneurysms (DREAM and EVAR I trials), and
      endovascular repair with no intervention in high-risk patients (EVAR 2 trial).
      DREAM and EVAR I showed that endovascular repair is associated with lower
      perioperative mortality, but overall survival is not improved after mid-term
      follow-up. EVAR 2 showed that high-risk patients do not benefit from elective
      endovascular repair. It can be concluded that relatively young and low-risk
      patients should be treated with open repair and that conservative treatment may
      be appropriate for high-risk patients. Between these extremes is a large group
      ofpatients who may benefit from endovascular repair. However, long-term follow-up
      data are not yet available and costs for endovascular therapy are substantial.

PMID- 16613247
TI  - [Dealing with medically unexplained symptoms in general practice: from irritation
      to 'the tricks of the trade'].
AB  - Patients with medically unexplained symptoms pose a problem for medical
      professionals. Doctors usually lack tools to handle these complaints adequately.
      Over the past decades much research has been done in the areas of classification
      and intervention both in general practice and in specialist care. If the doctor
      responds to the patient by offering to prescribe medicinal symptom relief, the
      first step into the vicious circle is taken. The patient is polite enough to try
      the medication but when it does not help, returns to the doctor. If the doctor
      continues to think along somatic lines the phenomenon known as iatrogenically
      enforced somatic fixation may arise. The main development in intervention stems
      from cognitive behavioural therapy, which is now considered the gold standard for
      all patients, regardless of their symptoms. In the Netherlands, a postgraduate
      course has been developed to implement the fundamentals of this approach into
      general practice. On this course, the doctor learns not to be deterred by the
      somatizing patient and to effectively close off their somatic treatment
      trajectory. He or she teaches the patient to look at the situation from a new
      perspective and instead of being preoccupied with what is not functioning well to
      concentrate on training those activities which can be carried out effectively.
      This shift in emphasis can help to cause the preoccupation of the patient to
      slowly disappear. Initial results are encouraging: both patients and general
      practitioners have responded favourably.

PMID- 16613248
TI  - [Medical assistance by doctors on board an aircraft].
AB  - Medical assistance by doctors on board an aircraft The number of in-flight
      medical emergencies continues to increase due to the rise in the number of
      (older) passengers, the greater capacity of new airplanes and the constant
      increases in the distances flown. The most common medical problems on board an
      aircraft are vasovagal collapse, dizziness, and gastro-intestinal and cardiac
      complaints. According to Dutch law, a physician on board an aircraft is obliged
      to deliver medical assistance in case of a medical emergency involving a
      passenger if requested by the cabin crew. The chances of being involved in a
      lawsuit afterwards are, however, very small because the usual medical standards
      do not apply and because the patient usually does not know the doctor that has
      assisted him. Even if it should come to a legal procedure, the chance that a
      physician will be found guilty of malpractice is very small because of the
      special circumstances and limitations in an airplane.

PMID- 16613249
TI  - [The guideline 'Treatment of acute carbon-monoxide poisoning' from doctors in
      clinics with a tank for hyperbaric ventilation].
AB  - The guideline 'Treatment of acute carbon-monoxide poisoning' from doctors in
      clinics with a tank for hyperbaric ventilation Carbon-monoxide (CO) poisoning is
      a potentially life-threatening emergency. Its prognosis is determined by prompt
      recognition and treatment. CO is toxic because it binds to haemoglobin (Hb), thus
      impairing oxygen transport and causing tissue hypoxia. The most important
      symptoms are headache and altered consciousness, ranging from somnolence to coma.
      The diagnosis is based on a history ofCO exposure combined with an elevated
      carboxyhaemoglobin (HbCO) level in the blood. On the basis of the available
      literature, it is recommended that patients with a HbCO level > or = 10% should
      always be treated. In patients requiring artificial ventilation, 100% oxygen for
      8 hours is recommended. In pregnant women and in patients who are or have been
      comatose, hyperbaric oxygen can be considered. In all other symptomatic patients,
      use of a non-rebreathing mask with 100% oxygen for 8 hours is recommended.

PMID- 16613250
TI  - [Diagnostic image (267). A man with a painful ulcer on the finger].
AB  - A 28-year-old man presented with severe ulceration on the right middle finger and
      erythematous nodules on the forearm due to infection with Mycobacterium marinum
      after cleaning an aquarium.

PMID- 16613251
TI  - [Somatoform disorders in general practice: prevalence, functional limitations and
      comorbidity with anxiety and depression].
AB  - OBJECTIVE: To quantify the prevalence of, and functional impairment associated
      with, somatoform disorders in general practice and their comorbidity with anxiety
      and depression. DESIGN: Prevalence study. METHOD: In the first phase of a two
      stage prevalence study from April 2000 up to December 2001, a questionnaire was
      completed by 1046 consecutive attendees at general practices, aged 25-79 years (n
      = 1778). This was followed in the second phase by a standardised diagnostic
      interview ('Schedules for clinical assessment in neuropsychiatry'; SCAN 2.1) in a
      stratified sample of 473 patients. In the analyses, the prevalence figures were
      estimated by weighting back to the original attending population. RESULTS: The
      prevalence ofsomatoform disorders was 16% (95% CI: 12.8-19.4). Comorbidity of
      somatoform disorders and anxiety or depression disorders was 3.3 times more
      likely than would be expected by chance. Somatoform disorders as well as anxiety
      or depressive disorders were associated with substantial functional impairment.
      In patients with comorbid disorders, physical symptoms, depressive symptoms and
      functional limitations were proportionately increased. CONCLUSION: These findings
      underline the importance of a comprehensive diagnostic approach covering anxiety
      and depressive disorders as well as somatoform disorders in general practice.

PMID- 16613252
TI  - [Ovarian tumour in a girl with chronic abdominal pain and distension].
AB  - A 12-year-old girl presented with chronic abdominal pain and distension that had
      persisted for 6 and 3 months, respectively. The cause was a Sertoli-Leydig cell
      tumour originating in the left ovary. The cyst and ovary were resected. The
      patient recovered and was asymptomatic 2 years after the operation. Ovarian
      tumours are rarely seen in children. The sex cordstromal tumours constitute a
      heterogeneous subgroup. Two of the most frequently observed sex cord-stromal
      tumours are the juvenile granulosa cell tumour and the Sertoli-Leydig cell
      tumour. Even though these tumours may contain histologically malignant
      characteristics, their behaviour is usually benign. Clinical characteristics are
      endocrine symptoms, fatigue, chronic abdominal pain and abdominal distension. In
      addition, pressure from the tumour mass may result in symptoms in adjacent organ
      systems. Surgical excision is usually curative. Patients with advanced disease
      may benefit from adjuvant chemotherapy. Chronic abdominal pain is frequently
      observed in children and, in some rare cases, may be caused by ovarian tumours.

PMID- 16613253
TI  - [Acute pancreatitis in a hepatitis C positive patient following treatment with
      peginterferon alfa-2b and ribavirin].
AB  - A 59-year-old man, treated with peginterferon alfa-2b and ribavirin because of a
      chronic Hepatitis C virus infection presented in the emergency department with
      acute epigastric pain. An acute pancreatitis, probably toxic, was diagnosed. A
      literature search confirmed that acute pancreatitis may develop as a result of
      treatment with (peg)interferon whether or not in combination with ribavirin. It
      is important to be aware of pancreatitis when patients treated with these
      medications present with acute epigastric pain. Discontinuing the medication will
      lead to a rapid reduction of the symptoms and recovery.

PMID- 16613254
TI  - [Guideline on the use of corticosteroids in Duchenne muscular dystrophy from
      paediatric neurologists, neurologists and rehabilitation physicians].
AB  - A guideline on the treatment of boys with muscular dystrophy with corticosteroids
      has been written and is available from the Dutch patients' organization. The
      guideline has been approved by the Dutch Societies of Neurology, Rehabilitation
      and Paediatrics. Based on the available literature the advice is to treat the
      boys with corticosteroids as soon as they become symptomatic. Prednisone is the
      drug ofchoice. The recommended dosage is 0.75 mg/kg body weight/day, every day or
      in a schedule of 10 days with treatment and 10 days without. From the initiation
      of the prednisone treatment dietary advice is given to control body weight.
      Monitoring for adverse effects takes place regularly.

PMID- 16613255
TI  - [Unexplained physical symptoms: a widespread problem but still low-profile in
      training programs and guidelines].
AB  - Unexplained physical symptoms or functional somatic syndromes that cannot be
      explained in terms of a defined medical disease are common. If persistent, they
      can cause significant distress and disability, and lead to absenteeism and social
      isolation as well as major health-care costs. Unexplained physical symptoms form
      a spectrum from transient unexplained mild physical symptoms to chronic severe
      somatoform disorders. Various functional somatic syndromes overlap one another
      substantially in symptomatology and are often resistant to conventional medical
      therapy. The 'Vereniging Nederlands Tijdschrift voor Geneeskunde' (Dutch Journal
      of Medicine Association) recently held a special conference on unexplained
      physical symptoms. The conclusions were: (a) patients are reluctant to accept the
      diagnosis of unexplained physical symptoms, because physicians do not have
      sufficient knowledge, expertise, and skill to diagnose and treat them, (b)
      patients with unexplained physical symptoms do not necessarily need to be treated
      by a psychiatrist except in cases of chronic and serious somatoform disorder.
      Patients with unexplained physical symptoms, who often have multiple and complex
      problems, are best treated by a team of physicians and allied paramedical
      professionals; (c) patients with unexplained physical symptoms can be treated
      effectively by specialists using cognitive behaviour therapy. Different cognitive
      models are available; the 're-attribution model' focuses on the re-establishment
      of a liveable life, while 'the consequence model' is directed at reducing the
      consequences of the unexplained physical symptoms. Management using the
      attribution model may be followed up by the consequence model approach; (d) the
      development of a practice guideline for the diagnosis and treatment of patients
      with both acute and chronic unexplained physical symptoms would improve the
      quality of patient care, reduce disability, increase the possibility of
      reintegration, and stimulate scientific research; (e) both theoretical and
      practical training in the diagnosing and managing of unexplained physical
      symptoms is inadequate in both university curriculums and postgraduate training
      programmes for medical specialists. Scientific research for the development of an
      evidence-based practice guideline is urgently needed.

PMID- 16613256
TI  - [Evaluation of a programme for the prenatal screening for Down's syndrome by
      ultrasonographic nuchal translucency measurement and serum determinations in the
      first trimester of pregnancy].

PMID- 16613257
TI  - [Bacterial meningitis following spinal anesthesia].

PMID- 16613258
TI  - [Careless medical terminology].

PMID- 16613259
TI  - [A multi-centeric epidemiological survey on TCM syndrome in 1016 patients with
      IgA nephropathy and analysis of its relevant factors].
AB  - OBJECTIVE: To investigate the distribution pattern of TCM syndrome in patients
      with IgA nephropathy and its relationship with the main clinical prognostic
      indexes to provide a basis for the standardization of integrative medicine in
      diagnosis and treatment of IgA nephropathy. METHODS: Multi-centeric
      epidemiological field survey was adopted to collect the materials of 1016 IgA
      nephropathic patients, including demography, TCM syndrome and laboratory
      findings, for exploring the distribution pattern of TCM syndrome of IgA
      nephropathy patients. RESULTS: Probability of over 10% could be found in the TCM
      syndromes as yin deficiency, qi deficiency, yang deficiency, damp-heat and blood
      stasis syndrome, the highest (41.5%) was found in qi-yin deficiency syndrome and
      the lowest (8.1%) in yang deficiency of Pi and Shen. Along with the increasing of
      age, the percentage of patients with Pi-Fei qi asthenia syndrome descended while
      those with Pi-Shen yang asthenia ascended. In the accompanying syndromes, damp
      heat syndrome and blood stasis syndrome, with the proportion of 32.6% and 28.9%
      respectively, were the most frequently encountered. The levels of 24 h urinary
      protein, serum creatinine and urea nitrogen in patients with Pi-Fei qi asthenia
      syndrome, qi-yin deficiency syndrome and Gan-Shen yin asthenia syndrome were
      significantly lower than those in patients with Pi-Shen yang asthenia syndrome,
      respectively (P < 0.05), while the blood pressure in patients with Pi-Fei qi
      asthenia syndrome, and qi-yin deficiency syndrome were significantly lower than
      that in patients with Gan-Shen yin asthenia syndrome and Pi-Shen yang asthenia
      syndrome (P<0.01). CONCLUSION: Qi-asthenia and yin deficiency is the principal
      clinical manifestation of IgA nephropathy. TCM syndrome types are closely related
      with the prognostic indexes as urine protein, hypertension, renal lesion, etc.

PMID- 16613260
TI  - [Clinical study on effect of fluoxetine combined with Chinese medicine or tibetan
      drugs in treating senile depression in plateau district].
AB  - OBJECTIVE: To compare the ettect and side-ettect of fluoxetine and combination of
      fluoxetine and Chinese or Tibetan medicine in treating senile depression in
      plateau district. Methods Ninety patients with diagnosis of senile depression
      conformed to CCMD-3 standard, in plateau district of 2260 - 3200 m altitude were
      randomly divided into three groups and treated with fluoxetine (group A),
      fluoxetine plus Sanpu Xinnao Xin granule (group B) and fluoxetine plus Xiaoyao
      pill (group C), respectively, 30 cases in each group. Therapeutic effects were
      evaluated with Hamilton' s depressive scale (HAMD) and treatment emergent symptom
      scale (TESS) after 6 weeks treatment. RESULTS: There was no significant
      difference in the therapeutic effects between the three groups. The adverse
      reaction in Group B and C was less than that in Group A (P<0.01). Conclusion
      Sanpu Xinnao Xin granule and Xiaoyao pill can raise the tolerance of patients
      with senile depression in plateau area against the adverse reaction of
      fluoxetine.

PMID- 16613261
TI  - [Protective effect of ligustrazine and propofol on peri-operational liver
      ischemia-reperfusion injury].
AB  - OBJECTIVE: To explore the protective effect and mechanism of ligustrazine (LGT)
      and propofol (PRO) on peri-operational liver ischemia-reperfusion injury (HIRI).
      METHODS: Thirty-six patients scheduled for hepatic surgery were randomly divided
      into the control group, the LGT group, the PRO group and the LGT + PRO group, 9
      patients in each group. Changes of superoxide dismutase (SOD), lipid peroxide
      (LPO), ratio of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto
      PGF1alpha), alanine aminotransferase (ALT) activity, and the ultrastructure of
      liver tissue were dynamically observed. RESULTS: Compared with the control group,
      SOD activity was significantly higher, LPO concentration, TXB2/6-keto-PGF1alpha
      ratio and ALT value were significantly lower (P < 0.05 and P < 0.01) in the LGT
      group, the PRO group and the LGT + PRO group during HIRI, with the abnormal
      changes of hepatic ultrastructure 25 min after reperfusion significantly
      alleviated in the three treated group. CONCLUSION: Combination of ligustrazine
      and propofol shows protective effect on liver by decreasing oxygen free radical
      level, reducing lipid peroxidation and adjusting TXA2/PGI2 imbalance after
      hepatic ischemia-reperfusion in patients undergoing hepatic cancer surgery.

PMID- 16613262
TI  - [Comparative study on two methods of back propagation network test in TCM
      syndrome typing of depression].
AB  - OBJECTIVE: To compare the effect of the two methods of back propagation network
      (BPN) test on TCM syndrome typing of depression. METHODS: Test was carried out by
      two methods as following: (1) Cross train-test method: 1731 patients with
      depression typed to 5 syndrome types were randomly divided into 2 groups, and
      they were trained and tested in turn; (2) Round-Robin method: Test was conducted
      in an altered cycle mode, that is, in a cycle, one out of the 1731 patients were
      selected to be tested, while the others were trained, the next cycle started when
      the test on the selected patient was finished and another one for test was
      selected. In this way, one cycle after the other, until all patients had been
      tested. RESULT: The total training sensitivity of the two methods was 97.9% and
      98.2% respectively, and the total testing sensitivity was 72.7% and 74.2%
      respectively. CONCLUSION: (1) The five TCM syndrome types of depression could be
      well differentiated by BPN, which is valuable for TCM syndrome typing in certain
      extent; (2) The sensitivity of Round-Robin method is slightly higher than that of
      Cross train-test method, but in comparison between them no remarkable
      significance was shown.

PMID- 16613263
TI  - [Clinical observation on effect of danzhi xiaoyao powder in treating depression].
AB  - OBJECTIVE: To observe the effect and side effect of Danzhi Xiaoyao powder (DXP)
      in treating depression. METHODS: A randomized controlled and double-blinded study
      was conducted in 63 cases of depression by divided them into the western medicine
      group (WMG, 31 cases) treated with maprotiline, and the Chinese medicine group
      (CMG, 32 cases) treated with DXP. The effect of therapy was evaluated before and
      at the 2nd, 4th and 6th week of the treatment with Hamilton's depressive scale
      (HAMD), self-rating depression scale (SDS), self-rating anxiety scale (SAS) and
      the scale for TCM syndrome and symptom differentiation (TCM-SSD), and the side
      effect of therapy was assessed with Asberg side-effect scale as well. RESULTS:
      There was no significant difference between the two groups in scores of HAMD,
      SDS, SAS, and TCM-SSD. The markedly effective rate in CMG was 84% and in WMG 87%,
      showed no significance between them (P > 0.05). The scores of HAMD, SDS and SAS
      of both groups were remarkably lowered after therapy (P < 0.05). However, the
      score of Asberg in CMG was lower than that in WMG (P < 0.05). CONCLUSION: DXP
      shows the effect equivalent to that of maprotiline, but with obviously less side
      effect.

PMID- 16613264
TI  - [Clinical study on preventive effect of fuzheng quxie granule on respiratory
      viral infection].
AB  - OBJECTIVE: To evaluate the effect of Fuzheng Quxie granule (FQG) on immune cells
      and cytokines of populations susceptible to respiratory viral infection. METHODS:
      One thousand four hundred and two subjects selected from 25 hospitals in Shanghai
      between May and June in 2003, were divided into the FQG group treated with FQG
      and the control group treated with placebo. Serum levels of interleukin 2 (IL-2),
      interleukin 4 (IL-4), gamma-interferon (gamma-IFN), blood lymphocyte subsets
      (CD3+ , CD4+, CD8+), B-cell count and natural killer cell (NK) percent ratio were
      measured in 130 of the FQG group and 120 of the control group before treatment,
      by the end of the 2nd week and two weeks after treatment. RESULTS: By the end of
      the 2nd week of treatment, as compared with before treatment, the levels of IL-2,
      gamma-IFN, and NK percent in the FQG group increased significantly (P < 0.05),
      while IL-4 and CD3+, CD4+, CD8+ and B-cell count were unchanged. Besides, levels
      of Th1/Th2 ratio markedly increased at the end of the 2nd week and two weeks
      after treatment, in comparing with that before treatment and in the control group
      (P<0.05). CONCLUSION: FQG could improve immune function of population susceptible
      to respiratory viral infection certain extent.

PMID- 16613265
TI  - [Preliminary study on intestinal flora in diarrhea type irritable bowel syndrome
      with pi-wei dampness-heat syndrome].
AB  - OBJECTIVE: To observe the changes of intestinal flora in diarrhea type irritable
      bowel syndrome with Pi-wei dampness-heat syndrome (IBS-PDS). METHODS: The seven
      kinds of common intestinal bacteria in feces, including enteri bacillus,
      enterococci, saccharomycete, bifid bacteria, lactobacillus, bacteroides and
      peptococcus were studied in 21 patients suffered from IBS-PDS, and compared with
      those in 22 patients with IBS with deficiency of Pi syndrome (DPS) and 25 healthy
      subjects as control. RESULTS: As compared with the healthy subjects, the levels
      of enteri bacillus and enterococci were significantly increased (P<0.01), the
      levels of bifid bacteria, Lactobacillus and Peptococcus were significantly
      decreased (P < 0.01), and saccharomycete and Bacteroides were insignificantly
      different in patients with PDS. As compared with patients with DPS, the levels of
      enteri bacillus, enterococci, bifid bacteria, Lactobacillus, Peptococcus and
      Bacteroidaceae were significantly increased except the level of saccharomycete.
      CONCLUSION: There may be alteration of intestinal flora in patients with IBS-PDS.

PMID- 16613266
TI  - [Effects of Xuezhikang on serum levels of high sensitive-C reactive protein,
      matrix metalloproteinase-9 and lipoprotein in patients with acute coronary
      syndrome].
AB  - OBJECTIVE: To investigate the effects of Xuezhikang (XZK) on serum levels of high
      sensitivity-C reactive protein (Hs-CRP), matrix metalloproteinase-9 (MMP-9) and
      lipoprotein in patients with acute coronary syndrome (ACS). METHODS: Sixty-nine
      ACS patients were divided into the XZK group (40 cases) treated with conventional
      therapy and XZK and the control group (29 cases) with conventional therapy alone,
      another 30 healthy persons were assigned as the normal group. Before and after
      the treatment, the levels of Hs-CRP, MMP-9 and lipids were detected. RESULTS:
      Compared with those in the normal subjects, Hs-CRP and MMP-9 levels in the ACS
      patients increased significantly (P <0.05), parallel with the extent of
      myocardial injury. After 2 weeks of XZK treatment, levels of Hs-CRP and MMP-9 of
      the XZK group decreased significantly (P <0.05), while lipids levels had no
      remarkable changes. CONCLUSION: Hs-CRP and MMP-9 levels were closely correlated
      to the genesis and severity of ACS. Anti-inflammatory action of XZK plays an
      important role in early stage treatment of ACS patients.

PMID- 16613267
TI  - [Dynamic change of metabolism related protein in liver tissue of rats' model of
      hepatic fibrosis and regulatory effect of fuzheng huayu decoction on it].
AB  - OBJECTIVE: To investigate the effect of Fuzheng Huayu decoction (FHD)
      intervention on hepatic fibrosis. METHODS: Wistar rats were randomly divided into
      3 groups: rats in the normal group only treated with subcutaneous injection of
      saline, rats in the model group and the FHD group were made into hepatic fibrosis
      by subcutaneous injection of 40% carbon tetrachloride (CCl4)-olive solution and
      then those in the FHD group were treated with FHD by gastric perfusion after
      modeling. Liver samples of the rats were obtained for routine pathological
      observation, hydroxyproline determination and proteome quantitative
      determination. After then, the proteome profile was obtained through 2
      dimensional electrophoresis and silver staining, and analyzed. More than 30
      proteins with different expression were identified by MALDI-TOF-MS. RESULTS: (1)
      The integral response of vital movement such as body weight and activity of
      hepatic fibrosis declined in the CCl4 induced liver fibrosis rats; (2) Liver
      fibrosis were associated with abnormal metabolism; (3) There were four material
      metabolism-related protein showed by hepatic proteome mass spectrography, which
      expressed different between the normal and the fibrotic rats, i. e. the
      perchloric acid soluble protein, the phosphatidylinositol transferase, the
      phosphoglycerate kinase and the endoplasmic reticulum-60 protease; (4) The
      expressions of the above-mentioned four proteins in the FHD group were nearly the
      same as those of normal level. CONCLUSION: (1) Liver fibrosis is accompanied with
      abnormal protein synthesis and decomposition, as well as the enhanced activity of
      glycolysis; (2) The existence of metabolism-related proteins is one of the
      elements for the liver in regulating metabolism; (3) The regulation on the
      expressions of metablism-related proteins is one of the pathways for FHD to exert
      its anti-hepatic fibrosis effect.

PMID- 16613268
TI  - [Nuclear factor-kappaB mRNA and protein expression in stomach tissue of rats with
      gastric ulcer recurrence and effect of jianwei yuyang granule on its expression].
AB  - OBJECTIVE: To observe the inflammatory reaction, nuclear factor-kappaB (NF
      kappaB) mRNA and protein expression in stomach tissue of rats with gastric ulcer
      recurrence and the effect of Jianwei Yuyang granule (JYG) on them. METHODS:
      Gastric ulcer and its recurrent lesion were successively induced by acetic acid
      and interliukin1-beta (IL-1beta), and the model rats were divided into the sham
      operation group, the model group, the omeprazole (correction of omepraxole) group
      and the JYG group to observe the state of chronic inflammatory cell, neutrophil
      count, NF-kappaBmRNA and protein expression in stomach tissue. RESULTS: On the
      16th and 92th day after administration, the increase of chronic inflammatory
      cell, neutrophil, NF-kappaBmRNA and protein expression in the model group was
      more significant than those in the sham operated group (P < 0.01), while that was
      lower in the JYG group than in the model group (P < 0.05, P <0.01), but with no
      remarkable difference to the omepraxole group. In addition, the mRNA and protein
      expression of NF-kappaB were correlated closely with the count of chronic
      inflammatory cell and neutrophil respectively (P < 0.01). CONCLUSION: NF-kappaB
      may play an important role in regulating inflammatory reaction during the healing
      and recurrence processes of gastric ulcer induced by acetic acid. JYG may
      suppress inflammatory reaction by inhibiting the activation and expression of NF
      kappaB in stomach tissue, which may be one of the mechanisms of JYG in preventing
      the recurrence of gastric ulcer.

PMID- 16613269
TI  - [Effects of huanglian jiedu decoction on leptin and resistin in insulin resistive
      rats].
AB  - OBJECTIVE: To study effects of Huanglian Jiedu Decoction (HJD) on lipid
      metabolism, leptin and resistin in insulin resistive rats. METHODS: Type 2
      diabetes mellitus (DM2) rat model was induced by intravenous injection with a low
      dose of streptozotocin and high fat and high caloric diet, and randomized into
      four groups: the model control group, the HJD group, the berberine group and the
      aspirin group. Meanwhile 16 normal rats were assigned as the normal control
      group. The body weight was observed before and after treatment, total cholesterol
      (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C),
      apolipoprotein A1 and B (apoA1, apoB), free fatty acid (FFA), insulin (INS) in
      serum, skeletal muscle triglyceride (mTG) in skeletal muscle, and oral glucose
      tolerance test (OGTT) and fasting blood glucose (FBG) were detected after 10
      weeks of treatment, at the same time, serum levels of leptin and resistin were
      determined using ELLISA. RESULTS: The levels of TC, TG, apoB, FBG, FFA, mTG,
      leptin and resistin were obviously lowered, the levels of HDL-C and apoA1
      significantly raised, glucose tolerance improved and body weight reduced in
      insulin resistive rats, as compared with the model control (P<0.05, P<0.01).
      CONCLUSION: The effects of HJD in lowering lipids, as well as reducing leptin and
      resistin might be closely correlated with its effects in ameliorating insulin
      resistance.

PMID- 16613270
TI  - [Effect of prepared radix Polygoni multiflori on the elevation of extracellular
      hydroxyl radical in striatum of rats induced by intracerebral perfusion of 6
      hydroxy dopamine].
AB  - OBJECTIVE: To investigate the effect and mechanism of prepared Radix Polygoni
      Multiflori (RPM) on the elevation of extracellular hydroxyl radical in striatum
      of rats induced by intracerebral perfusion of 6-hydroxy dopamine (6-OHDA).
      METHODS: Cerebral microdialysis was used to establish the model. Hydroxyl radical
      was captured by salicylic acid, and 2,3-dihydroxy benzyl acid (2,3-DHBA) and 2,5
      dihydroxy benzyl acid (2,5-DHBA) formed by hydroxyl radical in vital brain were
      measured by high performance liquid chromatography-electrochemical detector (HPLC
      ED). RESULTS: After perfusion of 6-OHDA in brain of rats, the levels of 2,3-DHBA
      and 2,5-DHBA in the model group increased rapidly. The former was higher during
      the whole course of observation (P<0.01), while the latter was higher at most
      time points than that in the control group (P<0.05 or P<0.01). The level of 2,3
      DHBA in the RPM group was lower than that in the model group at 5 time points (P
      < 0.05, P < 0. 01). CONCLUSION: RPM could inhibit the elevating of extracellular
      hydroxyl radical in striatum of rats induced by intracerebral perfusion of 6
      OHDA, indicating one of the brain protective mechanisms of RPM may be related to
      its anti-oxidation effect.

PMID- 16613271
TI  - [Effect of ginkgo biloba extract and dipyridamole on transcription and
      translation of inducible NO synthbase in rabbits after myocardial ischemia
      reperfusion injury].
AB  - OBJECTIVE: To investigate the effects of Egb761, an extract of ginkgo biloba ,
      and dipyridamole on inducible NO synthase (iNOS) in rabbits after myocardial
      ischemia-reperfusion injury. METHODS: After being established into ischemia
      reperfusion injury model, 35 rabbits were divided randomly into 5 groups: Group A
      (the sham group), Group B (the model group), Group C (treated with dipyridamole
      0.8 mg/kg), Group D (treated with Egb761, 40 mg/kg), and Group E (treated with
      Egb761 40 mg/kg combined with dipyridamole 0.8 mg/kg), all the medications were
      administered by intravenous injection 30 min after reperfusion. After
      administration, myocardial iNOS mRNA expression was detected by RT-PCR and
      western blot. RESULTS: Myocardial iNOS mRNA transcriptive expression in the 5
      groups were A 0, B 157.11 +/- 17.73, C 202.6 +/- 21.84, D 356.13 +/- 24.18 and E
      562.34 +/- 35.19 respectively, showing significant difference between the treated
      groups and group B (P <0.01). The translative expression of myocardial iNOS in
      the 5 groups were A 34.24 +/- 15.78, B 75.70 +/- 13.71, C 116.89 +/- 22.57, D
      143.75 +/- 16.05 and E 195.09 +/- 22.25 respectively, showing significant
      difference between the treated groups and group B as well (P < 0.05, P < 0.01).
      CONCLUSION: Both Egb761 and dipyridamole could increase myocardial iNOS
      expression in transcriptive and translative levels in rabbits after myocardial
      ischemia-reperfusion injury, and the combined treatment of them shows a more
      significant effect.

PMID- 16613272
TI  - [Effect of new qingkailing injection on cerebral edema following intracerebral
      hemorrhage in rats].
AB  - OBJECTIVE: To investigate the effect of New Qingkailing injection (NQKLI) on
      cerebral edema following intracerebral hemorrhage (ICH) induced by collagenase
      VII in rats. METHODS: After being established into ICH model by collagenase VII,
      rats were treated with NQKLI by intraperitoneal injection. Forty-eight hrs later,
      brain contents of water was detected with wet and dry method, calcium content in
      brain was detected by atomic spectrophotometer, tumor necrosis factor-alpha (TNF
      alpha) in brain tissue was determined by liquid competitive ibhibitory
      immunoassay, and serum matrix metalloproteinase-9 (MMP-9) were detected with
      enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: NQKLI reduced
      the contents of water, calcium and TNF-alpha content of brain tissue and serum
      MMP-9 in rats with ICH. CONCLUSION: NQKLI could alleviate both vasogenic and
      cytotoxic cerebral edema by prohibiting calcium over-load, protecting basilar
      membrane and eliminating inflammation.

PMID- 16613273
TI  - [Clinical observation on liang's anti-rheumatism and rheumatoid granule in
      rheumatoid arthritis in the active stage].
AB  - OBJECTIVE: To evaluate the therapeutic effect of Liang's anti-rheumatism and
      rheumatoid granule (LARG) in treating patients with rheumatoid arthritis (RA) at
      the active stage. METHODS: Fifty patients were administered orally with LARG in
      the treated group, 30 patients were treated with Wangbi granule in the control
      group. Symptoms, physical signs and relevant laboratory indexes in the 2 groups
      were observed and compared before treatment and after being treated for 2 months.
      RESULTS: The total effective rate and curative-markedly effective rate in the
      treated groups were superior to those in the control group (P <0.01). The
      improvement in aspects of integral scoring of symptom and physical signs,
      including arthragia, tumefaction, dysfunction indexes, morning stiffness and 15m
      walking time, and laboratory indexes, including blood sedimentation rate,
      rheumatoid factor, C creative protein, immunoglobin, as well as hemorheology
      relevant indexes in the treated group after treatment were significantly
      different to those before treatment and those in the control group (P <0.05 or P
      <0.01). CONCLUSION: LARG has obvious therapeutic effect on RA at the active
      stage.

PMID- 16613274
TI  - [Application of electro-acupuncture-anesthesia device in brachiplex nerve
      blocking].
AB  - OBJECTIVE: To investigate the effect of electro-acupuncture-anesthesia device
      (EAAD) as an auxiliary localizing method for brachiplex nerve blocking. METHODS:
      One hundred and twenty patients scheduled for operation in upper limbs were
      randomly divided into group A and group B, 60 in each group. Bupivacaine 25 ml
      (0.375% in concentration) was used to block intermuscular plexus brachialis in
      the operation for anesthesia and EAAD was used for adjunctive localizing in group
      A, while in group B paresthesia elicitation was used. RESULTS: In group A, the
      blocking was complete in 56 cases and incomplete in 4, the anesthesia effect was
      superior to that in group B, complete in 46, incomplete in 9, and of inefficient
      in 5 (P < 0.01). CONCLUSION: EAAD provides a localizing method for plexus
      brachialis blocking more precise than paresthesia elicitation.

PMID- 16613275
TI  - [Short-term curative effect of electroacupuncture as an adjunctive treatment on
      schizophrenia].
AB  - OBJECTIVE: To compare the short-term curative effect of clozapine (CZ) and its
      combination with electroacupuncture (EA) in treating schizophrenia. METHODS:
      Ninety schizophrenia patients were randomly divided into two groups equally: the
      EA group treated with combination of CZ (200 - 300 mg/d in mean) and EA, and the
      CZ group treated with CZ alone. The effects of treatment were evaluated with
      PANSS, CGI and TESS before and at the 2th, 4th, 6th and 8th weekend of the
      treatment. RESULTS: The initiation of effect in the two groups was the same, the
      total effective rate was 75% in the EA group and 73% in the CZ group. However,
      somatic complaint was lower and compliance was higher in the EA group than that
      in the CZ group respectively. CONCLUSION: With the effect equal to CZ,
      combination of CZ and EA shows higher compliance in treating schizophrenia, which
      would be beneficial in the later stage treatment for consolidation.

PMID- 16613276
TI  - [Protective effects of puerarin against myocardial injury in patients with
      hypertension during perioperational period].
AB  - OBJECTIVE: To investigate the protective effects of puerarin against myocardial
      injury in patients with hypertension during perioperational period. METHODS:
      Thirty-four patients with hypertension underwent general anesthesia were randomly
      divided into the control group and the puerarin group, 500mg puerarin was given
      to the puerarin group 1hr before anesthesia induction by venoclysis and to the
      control group, normal saline was given instead. The concentration of serum
      cardiac troponin I (cTnI) and isoenzyme of creatine kinase containing M and B
      subunits (CK-MB) were measured before anesthesia induction and 2 hrs after
      operation respectively. RESULTS: The serum concentration of cTnI and CK-MB were
      insignificantly different in the two groups before induction, the two indexes
      increased in different degrees (P <0.01) 2 hrs after operation in both groups,
      but the increments in the puerarin group were significantly lower than those in
      the control group (P< 0.01). CONCLUSION: Stress of operation and anesthesia could
      induce myocardial injury in patients with hypertension, which can be prevented by
      puerarin medicated during perioperational period.

PMID- 16613277
TI  - [Exploration on thinking approach and methodology of syndrome standardization].
AB  - The researching thinking approach of "descending the dimension with the lowering
      rank, ascending the rank with the raising of nsion of dimension", which could
      exclude the intervention of non-crucial fact ors and reveal the complexity of
      syndrome as well, provides a feasible approach for syndrome standardization. A
      study was conducted by analyzing some syndromes and their correlated factors
      selected from the "Ancient Good-sized Medical Records Database" through
      unconditional logistic multivariate stepwise regression by SAS 6.12 universal
      statistical software to sieve the variable, and the mathematical mode of
      regression equation was obtained eventually, expressed as logit (p) = alpha +
      beta1X1 + beta2X2 + ... + betamXm. With that, the research of syndrome
      standardization was proceeded on the syndromes with diagnostic significance to
      provide references for standardization of syndrome differentiation. I

PMID- 16613278
TI  - [Gaseous signaling molecule and study on activating blood circulation and
      removing stasis].
AB  - The finding of gaseous signaling molecule NO, CO and H2S, and the advocacy of
      "gas biology" concept have provided a novel thinking for the study of Huoxue
      Huayu (HXHY, a traditional Chinese medicine method of promoting blood circulation
      to remove blood stasis). The concept "Qi" in TCM and gaseous signaling molecule
      are correlated in respects of their source and mesomeric function. Study of HXHY
      could only be deepened through an overall cognition on blood stasis syndrome with
      the view of Qi-blood correlation.

PMID- 16613279
TI  - [Application of morpheme translation method in english translation of TCM].
AB  - In this paper, application of morpheme translation method in English translation
      of TCM was introduced, and its superiorities and limitations were analyzed in
      order to promote the standardization and improve the confused current status of
      the English translation of TCM.

PMID- 16613280
TI  - [Current situation of the study on treatment of bacteria translocation with
      integrated traditional Chinese and Western medicine].
AB  - Bacteria translocation (BT) induced enterogenous infection in multiple organs
      dysfunction syndrome (MODS) is closely related with the stress pyemia and MODS.
      For prevention of BT, western medicine stresses to improve the blood and oxygen
      supply of intestinal tract, mucosa protection, and application of microorganism
      preparation, while traditional Chinese medicine could also win good effect by
      using such drugs as rhubarb, red sage root, and compound decoctions.

PMID- 16613281
TI  - [Current situation of research and problems in diagnosis and treatment of senile
      depression with integrative traditional Chinese and Western medicine].
AB  - This paper summarized the researches on diagnosis and treatment of senile
      depression with integrative Chinese and Western medicine in the recent 5 years,
      and some problems existed at present were also submitted. It is pointed out that
      it's necessary to expand the study with senior electrocerebral neurotransmitter
      analysis technique (SET) for the diagnosis and efficacy evaluation of senile
      depression by either traditional Chinese or Western medicine. By which it would
      also be able to offer convincing evidence for diagnosis of depression, TCM
      syndrome differentiation dependant therapy and the efficacy evaluation.

PMID- 16613282
TI  - [Minute of the Seventh National Conferences of Integrative Chinese and Western
      Medicine on Cardiovascular Disease].

PMID- 16613284
TI  - [Organization in poles, a hospital experience].

PMID- 16613285
TI  - [Empathic patient care--an endangered art of symptomatic therapy].
AB  - It is essential that empathic and tender care assumes top priority in any
      physician's work despite or because of hightech medicine. Provision of care is
      not taught sufficiently in medical school and is not adequately trained during
      postgraduate formation mostly due to administrative overload. In addition,
      financial incentives are poorly developped. However warm patient care adds
      important personal value to any patient contact for the physician and protects-
      in the right dose--efficiently against a burnout syndrome. Some practical hints
      help the practising to regain some of this professional quality despite a highly
      rationalized health care system.

PMID- 16613286
TI  - [Symptomatic surgery].
AB  - We can distinguish between symptomatic and aetiological surgery. Symptomatic
      surgery includes operations, which remove the symptoms of a disease or at least
      palliate them albeit without removing their underlying pathology. On the other
      hand aetiological surgery means the curative removal of a pathology. It can be
      argued that any type of a surgery is symptomatic in nature, but that a part of
      the symptomatic surgery is curative as well. In addition to symptomatic and
      curative surgery, we also apply prophylactic surgery. Prophylactic surgery
      constitutes a controverse chapter. The question is whether an indication for
      prophylactic surgery does exist. One can argue, that it is difficult to improve
      the life of a well being patient by operating on him. On the other hand the
      question is whether it would not be more intelligent to improve the condition of
      a patient by removing the pathological aspects before symptoms appear. In
      addition, a pathological situation should not be allowed to progress to the stage
      where neither surgery nor conservative treatment offer sufficient benefit to
      patients.

PMID- 16613287
TI  - [Bereavement, burn out and chronic pain--symptomatic treatment with
      antidepressants].
AB  - Antidepressants can also be useful for non-classical indications such as
      bereavement, burn out and pain, if these conditions lead into a depressive
      episode or if additional effects like modulation of pain are of therapeutic
      benefit. Due to the range of side-effects and potential interactions, present
      medical condition, medication and the clinical appearance of the depressive
      episode have to be taken into account for the choice of the specific
      antidepressant. Patients need to be thoroughly informed and accompanied to build
      and sustain compliance. Patient's sceptical attitude towards antidepressants must
      be taken seriously and the risk of treatment needs to be considered.

PMID- 16613288
TI  - [Fever--useful or noxious symptom that should be treated?].
AB  - Fever is a phylogenetically ancient host reaction to invading microorganisms and
      other noxious stimuli. Poikylothermic organisms can reach febrile temperatures by
      seeking a hot environment in response to a higher set point in their
      thermoregulatory center. Endothermic organisms produce febrile temperatures
      through endogenous heat production at the expenditure of a higher metabolic rate.
      Nevertheless, fever has been conserved during evolution through millennia,
      obviously because of its advantage for host defense. Despite of these arguments
      most doctors, nurses and patients treat fever with antipyretics. The role of
      fever for the recovery from low risk infections is marginal at best. A large
      study of ibuprofen in patients with severe sepsis could not establish a positive
      or negative role on the course or final outcome of the infection in an intensive
      care setting. These clinical observations seemingly contradict findings in severe
      experimental bacterial infections in rodents but it has to be taken into
      consideration that these animals, in contrast to patients, received no antibiotic
      treatment. In patients with influenza-like illnesses non-steroidal antirhumatics
      (NSAR) improve fever and wellbeing with little or no evidence for undesired side
      effects. It therefore appears appropriate to treat patients with these and
      similar infections with NSAR. Antipyretic therapy in special patient groups such
      as brain injury victims, patients with cardiac or respiratory failure or dementia
      has not been established to be indicated to overcome a worsening of these organs
      to fail during infections. In children with a history of fever convulsions
      prevention or lowering of fever does not reduce recurrence. In patients with
      strokes it appears advisable however to use antipyretics in case of fever despite
      of a present lack of a proven beneficial effect. In conclusion symptomatic
      antipyretic therapy should be considered for low risk infections if patient
      suffering from fever. For more severe infections antipyretic therapy can be
      applied on an individual basis without too much hope to improve outcome or cause
      a severe worsening of prognosis.

PMID- 16613289
TI  - [Cough as a symptom--clarify or treat empirically?].
AB  - Cough is one of the most prevalent symptoms for which patients seek the attention
      of their physicians. Cough may serve as a protective reflex but can also impair
      social well-being and can profoundly and adversely affect patient's quality of
      life. Short and self-limited cough often does not require therapy, whereas
      prolonged cough is bothersome and should prompt further workup. If possible, the
      underlying cause should be identified and treated accordingly. Often, the patient
      history helps to establish a working hypothesis, such as possible post-nasal drip
      syndrome or gastroesophageal reflux as a cause. Asthma, another frequent cause of
      prolonged cough, is readily diagnosed in most cases. The response to empirical
      therapy often "confirms" a suspected etiology, if not, extensive workup involving
      function testing such as bronchoprovocation, radiology, endoscopy, and extended
      search for exceptional causes is warranted. Productive cough is often related to
      a bronchopulmonary disease, whereas an irritant cough is often of an
      extrapulmonary origin.

PMID- 16613290
TI  - [Polymyalgia rheumatica--fibromyalgia-syndrome: symptoms, syndromes or
      diseases?].
AB  - Polymyalgia rheumatica and Fibromyalgia are probably not distinct clinical
      entities. Rather polymyalgia rheumatica is the common denomiator of a large
      spectrum of different diseases. The historical separation between Polymyalgia
      rheumatica and Giant-Cell Arteritis is no more clinically applicable in most
      cases. A better clinical approach is to view them as extrems of a continuum.
      Similarly, fibromyalgia is one manifestation of chronic pain syndromes of
      undetermined etiology. In addition, fibromyalgia can often not be delineated
      clearely from functional disorders, including depression.

PMID- 16613291
TI  - [Symptomatic therapy in general practice--art or ignorance?].
AB  - Symptomatic therapy is well established in our society. Selftreatment of people
      normally is symptomatic and symptomatic treatment is also very common in family
      practice. A special situation is symptomatic therapy as a diagnostic method.
      Preconditions, benefits and risks are discussed.

PMID- 16613292
TI  - [Headache from overuse of medication].
AB  - Medication overuse headache (MOH) occurs in about 1% of the general population. A
      marked increase of its prevalence has to be expected in the future, since more
      and more adolescents are subject to medication overuse. The revised International
      Classification of Headache Disorders contains detailed diagnostic criteria for
      headache due to particular groups of substances. They help recognizing MOH due to
      ergots, triptans, analgesics and opioids, and to distinguish them from each other
      MOH almost exclusively occurs in patients with a long history of migraine or
      chronic tension type headache, which suggests some genetic disposition. The
      treatment of choice of MOH is withdrawal of the causing drug. Long-term treatment
      for headache is ineffective during medication overuse. Relapse rate is variable
      depending on the substance overused, and may be considerable. Therefore,
      prophylaxis in patients with migraine or chronic tension type headache who do not
      yet suffer from MOH, is essential.

PMID- 16613293
TI  - [From understanding the pathophysiological mechanisms of dyspnea to the correct
      symptomatic treatment].
AB  - Breathing discomfort is one of the most common and distressing symptoms
      experienced by patients. Various pathophysiologic mechanisms underlie the symptom
      of dyspnea, and multiple mechanisms may be present in a given patient. The
      evaluation of the dyspneic patient must begin with a thorough history examining
      the key characteristics of the symptom, including quality, intensity, duration,
      frequency, and distress. The words utilized by patients to describe their
      breathing discomfort may provide insights into the underlying pathophysiology of
      their disease. Treatment for dyspnea should be selected based on the
      pathophysiologic mechanisms involved and not only according to the specific
      disease. Attempts are made to reduce mechanical impedance (by reducing lung
      hyperinflation by bronchodilators or surgical volume reduction), to reduce
      ventilatory demand (by exercise training), to improve inspiratory muscle function
      (by inspiratory muscle training), to alter breathing patterns, to begin
      supplemental oxygen therapy and to reduce central perception. It is often
      necessary to combine several treatment modalities in order to achieve a
      significant reduction in dyspnea.

PMID- 16613294
TI  - [Percutaneous transluminal coronary angioplasty--treatment of symptoms or
      treatment of cause?].
AB  - Percutaneous transluminal angioplasty is a highly efficient therapy of an acute
      arterial occlusion, particularly in the coronary system. Arteriosclerosis is the
      most common cause of an acute occlusion of a coronary artery. However,
      arteriosclerosis is not only limited to the coronary circulation but is a
      panarterial disease. The molecular characterization of the underlying disease
      process and, consecutively, the individual typing of arteriosclerosis forms the
      basis of a targeted, personalized drug therapy. First approaches of such targeted
      therapies to treat arterioscleroses are currently tested in randomized,
      controlled trials.

PMID- 16613295
TI  - [Symptomatic therapies in palliative medicine].
AB  - Palliative Care is an approach that improves quality of life of patients in
      complex situations with life-threatening illness. The relief of suffering is
      important. In this meaning palliative care has a lot to do with symptomatic
      therapy, because we can't treat the underlying illness. In spite all of that the
      knowledge of the illness, its possibilities of treatment and its prognosis are
      important to know, if we want do take good and wise decisions. With three
      examples I would like to show, how different decisions about therapies can be of
      the illness. The neuropathic pain can derive from different aetologies. There are
      multiple options of therapy, but we don't have a good test to predict which
      therapy will fit for which patient in pain. We have only one evidence-based
      pharmacological treatment of dyspnoea, that's morphine. The decision whether to
      give or not nutrition to a patient with advanced cancer or advanced dementia
      seems to be a difficult one. But if we have a look into the literature it's much
      easier to decied, because there is almost no advantage for the patient if we
      nourish him.

PMID- 16613296
TI  - Medication aides--what the laws and rules say.

PMID- 16613299
TI  - [Radiotherapy of breast carcinoma. 2005 version].

PMID- 16613300
TI  - Postprocedural monitoring of cerebral aneurysms: which method and what length of
      follow-up after intervention?

PMID- 16613301
TI  - Is diffusion tensor imaging at 3T useful in assessing tumor extension in brain
      tumors?

PMID- 16613302
TI  - Availability, indications, and technical performance of computed tomographic
      colonography: a national survey.
AB  - PURPOSE: To determine the availability, indications, and technique of computed
      tomographic colonography (CTC) in Sweden and to investigate opinions on its
      future role in colon imaging. MATERIAL AND METHODS: In May 2004, a questionnaire
      on CTC was mailed to all Departments of Radiology in Sweden, and one year later a
      telephone interview was conducted with the departments that intended to start a
      CTC service. RESULTS: Ninety-nine departments (83%) answered the questionnaire,
      indicating that 23/ 99 (23.2%) offered a CTC service. Reasons for non
      implementation of CTC were lack of CTC training in 34/73 (46.6%) and non
      availability of multi-detector row CT scanners in 33/73 (45.2%), while 26% were
      awaiting further scientific documentation on CTC. Incomplete colonoscopy was the
      main indication for CTC in 21/23 (91.3%) departments performing CTC. Dual
      positioning, room air insufflation, and thin-slice collimation were used in all
      the responding departments. The number of CTC studies performed varied from 1-5
      (26.1%) to more than 200 (17.4%). Intravenous contrast material was routinely
      administered by 9/23 (39.1%) departments. Out of 30 (39.5%) departments that in
      2004 intended to start CTC, 9 (30%) had done so by June 2005. A total of 32/99
      (32.3%) departments had therefore started CTC by June 2005. Half of the
      departments that replied believed that CTC would absolutely or probably replace
      barium enema in the future. CONCLUSION: The survey shows relatively limited
      diffusion of CTC practice in Sweden, with approximately one-third of radiology
      departments offering a CTC service, mostly on a small scale. A wider
      dissemination of CTC requires further scientific documentation of its capability,
      intensified educational efforts, and additional funding.

PMID- 16613303
TI  - Abdominal plain film findings in acute ischemic bowel disease differ with age.
AB  - PURPOSE: To evaluate the use and findings of abdominal plain film in acute
      ischemic bowel disease (AIBD) in different age subsets, and to correlate the
      clinical findings. MATERIAL AND METHODS: Eighty-nine radiographically examined
      patients with AIBD at Malmo University Hospital, Sweden between 1987 and 1996.
      RESULTS: In 89%, the plain film displayed pathologic signs. Bowel dilatation was
      more common in the elderly. Of 68 patients aged > or = 71 years, 19 (28%) had
      colon gas/fluid levels with/without colon dilatation, and of 19 patients > 84
      years 16 (84%) had small-bowel dilatation. Of 20 patients aged < 71 years, 1 (5%)
      had colon gas/fluid levels with/without colon dilatation, and 11 (55%) small
      bowel dilatation (P < 0.05; P < 0.05). Gasless abdomen was more common in the
      younger age group, noted in 5 of 20 (25%) patients aged < 71 years, compared to 2
      of 68 (3%) patients aged > or = 71 years (P = 0.001). Of the patients with
      diarrhea, 13 of 33 (40%) had colon gas/fluid levels with/without colon dilatation
      compared to 2 of 29 (7%) without (P = 0.003). In the elderly (> or = 71 years),
      48 of 53 (91%) patients with bowel dilatation on plain film died, compared to 11
      out of 16 (69%) without this finding (P < 0.05). CONCLUSION: Abdominal plain film
      findings differed with age. Bowel dilatation was more frequent in the elderly
      with AIBD, whereas gasless abdomen was more common in younger patients. The
      radiographic findings were associated with clinical symptoms and mortality.

PMID- 16613304
TI  - Transcatheter arterial embolization in patients with bleeding duodenal ulcer: an
      alternative to surgery.
AB  - PURPOSE: To evaluate the efficacy and safety of transcatheter arterial
      embolization (TAE) in patients with bleeding/rebleeding duodenal ulcers. MATERIAL
      AND METHODS: Over a 6-year-period, 40 consecutive patients with bleeding/
      rebleeding after endoscopic therapy and/or surgery for duodenal ulcer were
      included in the study. Superselective angiographic catheterization and coil
      embolization were performed by the same interventional radiologist. RESULTS:
      Lasting hemostasis was achieved in 26 of 40 patients (65%). Transfusion
      requirement was reduced from median 14 (range 3-35) units of blood before TAE to
      2 (range 0-53) units after TAE. Ten patients died, five because of continuous
      bleeding. No adverse effects as a result of TAE were seen. CONCLUSION: TAE is an
      effective and safe treatment in a significant proportion of patients with
      bleeding duodenal/rebleeding ulcers after therapeutic endoscopy and/or surgery.

PMID- 16613305
TI  - Multidetector computed tomography and neuroendocrine pancreaticoduodenal tumors.
AB  - PURPOSE: To investigate the accuracy of dedicated pancreatic multidetector
      computed tomography (MDCT) in the diagnosis of neuroendocrine pancreaticoduodenal
      tumors (NPTs). MATERIAL AND METHODS: MDCT and other imaging studies in patients
      with suspected NPTs were identified. Thirty dedicated MDCT studies were done in
      23 patients. Fourteen patients (16 operations) subsequently had surgery. Imaging
      reports were reviewed and findings compared with surgical findings and findings
      in other imaging studies. RESULTS: Patients with surgery: 19 NPTs (16
      extrapancreatic gastrinomas and 3 pancreatic NPTs) were identified at surgery.
      MDCT identified 16 and somatostatin receptor scintigraphy (SRS) 11 out of 19
      tumors. Endoscopic ultrasound detected 11 out of 14 NPTs. Patients without
      surgery: In 4 out of 9 patients, no NPTs were identified at MDCT. CONCLUSION:
      Dedicated MDCT of the pancreas can identify many NPTs, including small duodenal
      and periduodenal tumors, and the detection rate is better than reported in the
      older literature on CT.

PMID- 16613306
TI  - Effect of computer-aided detection on mammographic performance: experimental
      study on readers with different levels of experience.
AB  - PURPOSE: To evaluate the effect of computer-aided detection (CAD) on the reader's
      performance. MATERIAL AND METHODS: Four screening radiologists, two novice
      radiologists, and two residents with no prior experience in CAD read films of 200
      women without and with CAD. The films, including 16 screen-detected cancers and
      35 cancers "missed" on prior screening, were divided into two rollers: A (free
      time schedule) and B (prompted time schedule). Reading times were noted.
      Individual readings without and with CAD were compared, sensitivities and
      specificities were calculated. RESULTS: The sensitivity of CAD was 70.6% and
      specificity 15.8%. In 408 cancer readings, the screeners found 10 and other
      readers 7 new cancers with the aid of CAD. The screeners changed their opinion
      four times and others six times from true positive to false negative when CAD was
      negative. CAD output produced 12 versus 13 new false-positive findings
      respectively after 2352 readings. CAD did not significantly affect the reader's
      sensitivities/specificities regardless of the time limit (P = not significant).
      The use of CAD increased mean time for roller reading from 56 to 63 min (P =
      0.053). CONCLUSION: Screening radiologists benefited slightly more from CAD than
      other readers did, but no statistical significant difference was found in
      personal readings without and with CAD.

PMID- 16613307
TI  - Macrophage uptake of ultra-small iron oxide particles for magnetic resonance
      imaging in experimental acute cardiac transplant rejection.
AB  - PURPOSE: To discriminate between acutely rejecting and non-rejecting transplanted
      hearts using a blood pool contrast agent and T2* magnetic resonance imaging (MRI)
      in a clinical 1.5T scanner. MATERIAL AND METHODS: Allogeneic and syngeneic
      heterotopic heart transplantations were performed in rats. One allogeneic and one
      syngeneic group each received either the ultra-small iron oxide particle (USPIO),
      at two different doses, or no contrast agent at all. MRI was performed on
      postoperative day 6. Immediately after the MR scanning, contrast agent was
      injected and a further MRI was done 24 h later. Change in T2* was calculated.
      RESULTS: No significant difference in change in T2* could be seen between
      rejecting and non-rejecting grafts in either of the doses, or in the control
      groups. There was a difference between the allogeneic group that received the
      higher contrast agent dose and the allogeneic group that did not receive any
      contrast agent at all. CONCLUSION: In our rat model, measurements of T2* after
      myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not
      useful for the diagnosis of acute rejection.

PMID- 16613308
TI  - Magnetic resonance imaging-guided diskography and diagnostic lumbar 0.23T MRI: an
      assessment study.
AB  - PURPOSE: To describe the in vivo appearance of magnetic resonance imaging (MRI)
      diskograms of normal and degenerated lumbar intervertebral disks, and to evaluate
      the differences in imaging findings between sequential diagnostic MRI and MRI
      diskography. MATERIAL AND METHODS: Nine consecutive patients underwent MRI-guided
      diskography in order to determine possible pain provocation during puncture and
      contrast medium injection. All patients had preceding clinical suspicion of
      lumbar diskogenic pain and findings of lumbar disk degeneration in diagnostic
      (MRI, computed tomography (CT), plain radiography). A 0.23T open MRI scanner with
      interventional tools was used for imaging and instrument guidance. On all
      patients, a complementary diagnostic MRI study of the lumbar spine before and
      after the MRI-guided disk injection was performed, and subsequent axial MRI
      diskograms were obtained. RESULTS: A total of 25 disk punctures were initialized,
      and 25 MRI diskograms were obtained and their expression described. There was a
      correlation between the degenerative disk findings visualized by diagnostic MRI
      and MRI diskograms. CONCLUSION: The use of gadolinium contrast media in MRI
      guided diskography enables the evaluation of MRI diskograms. Our results suggest
      that MRI-guided diskography can be used to substitute conventional diskography or
      CT-diskography and as an augmenting method to assess diagnostic information upon
      degenerative processes of the lumbar spine.

PMID- 16613309
TI  - Indications of inflammation visualized by ultrasound in osteoarthritis of the
      knee.
AB  - PURPOSE: Ultrasound examination of a group of patients with osteoarthritis (OA)
      of the knee for signs of inflammation. MATERIAL AND METHODS: 71 knees in 71
      patients with osteoarthritis of the knee were examined with high-resolution gray
      scale ultrasound combined with color and spectral Doppler. The medial, lateral,
      and antero-superior compartments were examined. Hyperemia was identified as
      presence of color Doppler signals in the synovial membrane. Low resistance flow
      was defined as a resistive index < 0.80 on spectral Doppler. RESULTS: Synovial
      thickening was found in all knees; fluid in 61 patients; and hyperemia (color
      Doppler activity) in 51 patients. Of these, 44 had arterial flow on spectral
      Doppler - 36 with a low resistance flow. When present, fluid and color Doppler
      activity was found in all three compartments, but with uneven distribution.
      CONCLUSION: The finding in the majority of cases of both effusions on B-mode US
      and Doppler activity confirms that there is a varying degree of inflammation in
      knee OA as diagnosed by the ACR criteria.

PMID- 16613310
TI  - Evolution of the imaging tests in hemophilia with emphasis on radiography and
      magnetic resonance imaging.
AB  - Even before the discovery of X-rays in 1895 attempts were being made to classify
      the joint destruction that occurs in hemophilic arthropathy. The advent of
      radiography added impetus to the search for the optimum classification system.
      Subsequent attempts have included advanced imaging methods, especially magnetic
      resonance imaging (MRI). Because of its high spatial resolution and ability to
      visualize soft tissue abnormalities, MRI is ideally suited as the best way to
      classify arthropathy. A literature search was carried out to document and list
      all the imaging methods for hemophilic arthropathy that have been published up to
      the present. All published classification systems are discussed and listed in
      tables. MRI has superior imaging capability and will probably become the most
      important modality for radiological classification of hemophilic arthropathy in
      the future.

PMID- 16613311
TI  - Treatment of recurrent chordomas by percutaneous ethanol injection therapy and
      radiation therapy.
AB  - We report a case of recurrent sacral chordomas that have been successfully
      controlled by the combination therapy of percutaneous ethanol injection therapy
      (PEIT) and radiation therapy in a 71-year-old man. PEIT may be one of the
      adjuvant therapies for recurrent chordomas.

PMID- 16613312
TI  - Multi-slice computed tomography appearance of abscess of cavum septum pellucidum:
      a case report and review of the literature.
AB  - Abscesses involving the cavum septum pellucidum are rare and, owing to their
      location, detection may be difficult with routine conventional computed
      tomography (CT). Only a few isolated cases have been reported and mostly in
      children. We report a case of abscess involving the cavum septum pellucidum in an
      adult and its appearance on multi-slice spiral CT.

PMID- 16613313
TI  - Glioma assessment using quantitative blood volume maps generated by T1-weighted
      dynamic contrast-enhanced magnetic resonance imaging: a receiver operating
      characteristic study.
AB  - PURPOSE: To investigate the use of blood volume maps in the non-invasive
      separation of glioma grades. MATERIAL AND METHODS: T1-weighted quantitative
      dynamic contrast-enhanced magnetic resonance imaging was used to quantify the
      fractional intratumoral blood volume of 41 gliomas (World Health Organization
      (WHO) grades II-IV). Two methods, mean fractional intratumoral blood volume
      determination and a system based on thresholds for extracting the tumor pixels
      with the highest vascularization from the blood volume maps, were investigated by
      means of receiver operating characteristic (ROC) analysis. The thresholds were
      adjusted using the ROC curve area calculated using the trapezoid method. RESULTS:
      The ability to separate grade II (WHO) gliomas from grades III-IV was nearly the
      same for both methods (ROC curve area 0.941 (threshold) versus 0.932 (mean
      value)) and significantly greater than the ability to separate grade IV (WHO)
      gliomas from grades II-III (ROC curve area 0.792 (threshold) versus 0.787 (mean
      value)). The best correspondence with WHO glioma grading was achieved using
      thresholds corresponding to only the 5.2% of tumor voxels with the largest blood
      volume for separating grade II gliomas and 4% for separating grade IV gliomas.
      CONCLUSION: Use of the optimized threshold resulted in matching with the WHO
      grading system in 74% of cases.

PMID- 16613314
TI  - Tumor extension in high-grade gliomas assessed with diffusion magnetic resonance
      imaging: values and lesion-to-brain ratios of apparent diffusion coefficient and
      fractional anisotropy.
AB  - PURPOSE: To determine whether the apparent diffusion coefficient (ADC) and
      fractional anisotropy (FA) can distinguish tumor-infiltrated edema in gliomas
      from pure edema in meningiomas and metastases. MATERIAL AND METHODS: Thirty
      patients were studied: 18 WHO grade III or IV gliomas, 7 meningiomas, and 5
      metastatic lesions. ADC and FA were determined from ROIs placed in peritumoral
      areas with T2-signal changes, adjacent normal appearing white matter (NAWM), and
      corresponding areas in the contralateral healthy brain. Values and lesion-to
      brain ratios from gliomas were compared to those from meningiomas and metastases.
      RESULTS: Values and lesion-to-brain ratios of ADC and FA in peritumoral areas
      with T2-signal changes did not differ between gliomas, meningiomas, and
      metastases (P = 0.40, P = 0.40, P = 0.61, P = 0.34). Values of ADC and FA and the
      lesion-to-brain ratio of FA in the adjacent NAWM did not differ between tumor
      types (P = 0.74, P = 0.25, and P = 0.31). The lesion-to-brain ratio of ADC in the
      adjacent NAWM was higher in gliomas than in meningiomas and metastases (P =
      0.004), but overlapped between tumor types. CONCLUSION: Values and lesion-to
      brain ratios of ADC and FA in areas with T2-signal changes surrounding
      intracranial tumors and adjacent NAWM were not helpful for distinguishing pure
      edema from tumor-infiltrated edema when data from gliomas, meningiomas, and
      metastases were compared.

PMID- 16613315
TI  - Postprocedural monitoring of cerebral aneurysms.
AB  - The treatment of intracranial aneurysms has been revolutionized since the
      introduction of electrolytically detachable platinum coils in 1991. Since this
      basic innovation, many refinements of the embolic materials and techniques have
      emerged. Today, in Europe, half of all aneurysms are treated endoarterially and
      this share is growing. The reassuring results of the International Subarachnoid
      Aneurysm Trial (ISAT) have changed the treatment strategy from neurosurgical
      clipping to embolization. However, the role of these alternative modes of
      treatment varies between institutions and countries. An angiographic follow-up
      pattern after endovascular treatment has remained largely undefined and in the
      same way there has been much diversity in applying alternative imaging
      modalities. Although some institutions continue to perform intervalled digital
      subtraction angiography, magnetic resonance angiography has assumed an increasing
      role. A vast majority of patients with embolized aneurysms are eligible to be
      monitored solely by non-contrast three-dimensional time-of-flight technique.

PMID- 16613316
TI  - Survival time and period of catheterization in patients treated with percutaneous
      nephrostomy for urinary obstruction due to malignancy.
AB  - PURPOSE: To assess patient mortality and survival time, period of
      catheterization, and indications for percutaneous nephrostomy (PCN) withdrawal in
      patients treated with PCN for urinary obstruction due to malignancy. MATERIAL AND
      METHODS: A retrospective analysis of 151 patients treated with 257 PCNs in a 5
      year period was performed. Data on survival time, duration of catheterization,
      and clinical end-points for PCN treatment were collected. RESULTS: The median
      survival time of the patients was 255 days, while median catheterization time was
      62 days. The majority of patients (84) died with the catheter. Indications for
      PCN withdrawal were surgery, stent treatment, catheter displacement, and response
      to medical treatment. CONCLUSION: The majority of patients with malignancy
      treated with PCN have advanced disease and short life expectancy. Factors such as
      diagnosis, prognosis, economy, and the patient's preference influence the choice
      of urinary diversion method. However, PCN should be considered in patients with
      malignancy on grounds of safety and low cost.

PMID- 16613317
TI  - An unusual renal vascular anomaly: common origin of arteries to the lower poles
      demonstrated by a computed tomography angiography using 16-slice multidetector
      computed tomography.
AB  - Arterial connection between the left and right kidneys is extremely rare. Only
      eight cases of such anomalous conditions have been reported in the world
      literature and all were confirmed by invasive angiography or dissection. We
      report a patient with this vascular anomaly clearly demonstrated by 16-slice
      multidetector computed tomography.

PMID- 16613318
TI  - Prostate cancer diagnosis: even the experts disagree.

PMID- 16613319
TI  - Recommendations for the supervision of pathology assistants: association of
      directors of anatomic and surgical pathology.

PMID- 16613320
TI  - Characterization of human Rab20 overexpressed in exocrine pancreatic carcinoma.
AB  - In a large-scale analysis of gene expression in pancreatic cancer, we isolated
      the homologue of the mouse Rab20. The mouse protein was previously identified
      during a search for novel Rab proteins, a family of small GTP-binding proteins
      involved in the regulation of intracellular vesicular transport. The Rab20
      protein has no close relationship to any member of the Rab protein subfamily. In
      contrast to other members, it contains an insertion of 40 amino acids of unknown
      function and an inversion of 3 amino acids at the position corresponding to codon
      61 in p21ras proteins. Using immunofluorescence and immunoelectron microscopy, we
      localized the Rab20 protein in the vicinity of the Golgi apparatus. Rab20
      expression was detected by Western blot analysis in 11 of 11 pancreatic tumor
      cell lines and 7 of 8 primary pancreatic carcinomas. Absent or very faint
      expression was observed in normal pancreas cell extracts. Immunohistochemical
      analysis of Rab20 in tissues showed low or absent expression in normal pancreas
      and stronger expression in 15 of 18 exocrine pancreatic adenocarcinomas. Rab20
      was also detected in preneoplastic pancreatic intraductal neoplasia lesions,
      suggesting that its up-regulation may be an early event in pancreatic
      carcinogenesis.

PMID- 16613321
TI  - Correlation and significance of histopathological and clinical features in breast
      cancer with skin involvement (T4b).
AB  - A retrospective review was performed to investigate the prognostic significance
      and validity of the pathological and clinical TNM staging of noninflammatory skin
      involvement in breast cancer. In 128 tumors with histologically proven skin
      involvement and a size up to 5 cm (64% of the entire group), we distinguished
      clearly between group A) cases showing the classical clinical signs (cT4b) and
      those that do not, and between group B) carcinomas infiltrating the epidermis
      (pT4b) and those infiltrating only the dermis. We found only moderate concordance
      (kappa = 0.44) between the pathological and clinical TNM staging system. In the
      analysis of 80 patients with a tumor size from 2.1 to 5.0 cm, neither the
      appearance of classical clinical signs nor the histological diagnosis of
      infiltration of the epidermis was shown to be a relevant factor. In comparison to
      the control groups, similar clinicopathologic entities without significant
      differences in long-term outcome were observed. After regrouping of the patients
      having tumor infiltration of the papillary dermis from the control group into the
      study group (pT4), the study group showed a significant higher number of involved
      axillary lymph nodes (P = .014) and a more extensive lymph node involvement (pN3;
      P = .025). The combination epidermis-papillary dermis seems to be more a
      functional unit than the epidermis alone that is defined as the crucial and
      delineating factor in the TNM Classification. Our results challenge the validity
      of the TNM rules and recommendations concerning T4b breast cancer because it
      leads, in the majority of cases, to tumors of comparable extent and prognosis
      being placed in different categories.

PMID- 16613322
TI  - Prognostic value of detecting recurrent glioblastoma multiforme in surgical
      specimens from patients after radiotherapy: should pathology evaluation alter
      treatment decisions?
AB  - The prognostic significance of the histologic type and grade of gliomas at
      initial surgery is well established, but the value of histologic findings in
      resections after radiotherapy is unclear. Despite this uncertainty, pathologic
      interpretation of specimens after radiotherapy influences immediate treatment
      decisions. It is important to determine if, and to what extent, treatment
      decisions should be based on this information. We aimed to determine the
      prognostic value of pathologic evaluation in postradiation specimens from 54
      patients with similar clinical features who underwent a second surgery for the
      treatment of radiologic worsening after external beam radiotherapy. We
      categorized the specimens from the second surgery as either recurrent tumor
      (category 1) or radionecrosis (category 2). Patients in category 1 had actively
      proliferating neoplasms with classical features of glioblastoma, whereas patients
      in category 2 had no evidence of tumor in their surgical specimens. Cases in
      which a clear-cut definition could not be made were labeled indeterminate
      (category 3). Despite the morphological evidence of tumor, there were no
      significant differences between categories 1 and 2 in any of the survival
      parameters tested. The only difference between groups was higher frequency of
      iodine 125 (125I) placement at second surgery in category 1 patients (P <.028).
      Patients in category 1 with or without 125I treatment had similar survival
      characteristics. We conclude that histopathologic evaluation of postradiotherapy
      specimens was not helpful in predicting outcome or dictating further management.
      A comprehensive prospective study with advanced radiologic, pathologic, and
      molecular analyses may be more useful to determine prognostically valuable
      parameters.

PMID- 16613323
TI  - Prognostic impact of cholangiocellular and sarcomatous components in combined
      hepatocellular and cholangiocarcinoma.
AB  - Combined hepatocellular and cholangiocarcinoma (cHC-CC) is a rare type of liver
      cancer displaying both hepatocellular and cholangiocellular components. The
      cholangiocellular carcinoma (CC) in these tumors ranges from focal to prominent.
      Those cHC-CCs with sarcomatous features are reported to have a poor prognosis. To
      clarify whether the CC and sarcomatous component affects the prognosis, we
      classified 40 patients with cHC-CCs into 4 groups according to the presence of a
      sarcomatous component and the extent of the CC component. Seven (17.5%) tumors
      showed areas with a sarcomatous component. The remaining tumors were divided into
      a low-CC group (CC occupying <30% of the tumor, n = 12), a middle-CC group (30%
      60%, n = 15), and a high-CC group (>60%, n = 6). Vascular invasion was more
      frequently present in the high-CC and sarcomatous group than in the other groups
      (P = .0007). No lymph node metastasis occurred in either the low- or the middle
      CC groups, but it was detected in 3 (50%) cases of the high-CC group and in 2
      (29%) cases of the sarcomatous group (P < .0001). There was a tendency for tumor
      size to increase from the low- to the middle- to the high-CC group. The Ki-67
      labeling index values for the hepatocellular carcinoma, CC, and sarcomatous
      components were 11.4% +/- 12.9%, 25.4% +/- 18.3%, and 46.0% +/- 23.6%,
      respectively. The overall survival of patients in the high-CC and sarcomatous
      group was significantly poorer than that of patients in the low- and middle-CC
      groups (P = .0048). By multivariate analysis of overall survival, lymph node
      metastasis, histological subgroup, and vascular invasion were significant
      independent prognostic factors. A cHC-CC with a large CC component is as
      aggressive as cHC-CC with sarcomatous features.

PMID- 16613324
TI  - Current practice of diagnosis and reporting of prostate cancer on needle biopsy
      among genitourinary pathologists.
AB  - As there is a lack of hard data in the literature about many of the issues
      relating to diagnosing and reporting prostate cancer, we sought to survey current
      practices. A questionnaire was sent to 93 genitourinary pathologists with a
      response rate of 69%. Almost all respondents (95%) used formalin as fixative for
      needle biopsies. Unstained intervening sections were retained by 47%. Three
      levels of needle biopsies were used routinely by 63%. For verification of a
      diagnosis of cancer, high-molecular-weight cytokeratin was still the most
      commonly used immunohistochemical marker (91%), followed by p63 (58%) and alpha
      methylacyl-CoA-racemase (50%). Features considered pathognomonic for cancer were
      glomeruloid bodies (58%), collagenous micronodules (64%), circumferential
      perineural invasion (84%), and growth in fat (36%). With none of these present,
      39% required a minimum of 2 to 10 glands (median, 3) to diagnose cancer, whereas
      the others had no lower limit. A Gleason score was always given to even minute
      cancer foci by 86% and typically a Gleason score 6 was assigned (77%). Perineural
      invasion was mentioned by 86%. The extent of cancer on needle biopsies was
      quantified by all respondents with number of involved cores (80%) being the most
      commonly used measure. Linear extent was estimated by almost all, either as a
      percentage (80%) or millimeters of cancer length (41%) or both (22%). Measuring
      cancer from end to end or subtracting intervening benign tissue were almost
      equally common. For those general pathologists who would like to be in the
      mainstream of most urological pathologists, our survey data provide a guideline
      on how to diagnose and report prostate cancer.

PMID- 16613325
TI  - Arsenic trioxide inhibits DNA methyltransferase and restores methylation-silenced
      genes in human liver cancer cells.
AB  - In the present study, we investigated methylation status of the CpG islands of
      some major tumor suppressor genes both in human hepatocellular carcinoma and
      liver cancer cell lines and examined whether demethylation by arsenic trioxide
      (As2O3) could restore their expression in the cell lines. HepG2 and Huh-7 cells
      were treated with 2 to 10 micromol/L of AS2O3 and/or 1 micromol/L of 5-aza-2'
      deoxycytidine for 24, 48, and 72 hours. The methylation status of the CpG island
      around the promoter regions of p161NK4a, RASSF1A, E cadherin, and GSTP1 was
      detected by a methylation-specific polymerase chain reaction (MSP). The messenger
      RNA (mRNA) and protein levels of these genes were determined by quantitative real
      time reverse transcriptase-polymerase chain reaction, Western blot, and
      immunohistochemical analyses. The DNA methyltransferase (DNMT) mRNA levels and
      enzyme activity were also examined. The hypermethylated status of the promoter
      regions of p16INK4a, RASSF1A, E cadherin, and GSTP1 was observed in 10 (40%), 14
      (56%), 6 (24%), and 12 (48%) of 25 patients with hepatocellular carcinoma,
      respectively. CpG methylation of the p16INK4a, RASSF1A, E cadherin, and GSTP1
      genes was correlated to the reduction of mRNA levels in the cell lines, and mRNA
      expression of these 4 genes were indeed restored by low concentrations (2-6
      micromol/L) of As2O3 through demethylation, as well as 1 micromol/L of 5-aza-2'
      deoxycytidine. Western blot and immunohistochemical analyses confirmed that each
      protein was markedly enhanced after treatment with a low concentration of As2O3.
      In contrast, As2O3 at a high concentration (10 micromol/L) damaged cell membranes
      and remarkably suppressed these 4 protein levels. As2O3 decreased the mRNA
      expression of DNMT 1 and also dose-dependently inhibited DNMT activity. In
      conclusion, a low concentration of As2O3 induces CpG island demethylation of
      tumor suppressor genes by inhibition of DNMT and reactivates the partially/fully
      silenced genes in liver cancer cells.

PMID- 16613326
TI  - Calretinin expression in tumors of adipose tissue.
AB  - Although well established as a marker of mesothelial cells, calretinin is also
      expressed in several other tissue types, including adipose tissue. Accordingly,
      immunohistochemical staining for calretinin has been described in an increasing
      number of neoplasms other than mesothelioma. A detailed analysis of calretinin
      expression in lipogenic tumors has not yet been reported, however. Given the
      known expression patterns of calretinin in normal tissues, we predicted that
      calretinin immunoreactivity would be detected in lipoma and the various
      histologic subtypes of liposarcoma, and that this marker might be of use in the
      differential diagnosis of selected fatty tumors. A variety of pleomorphic and
      small round cell sarcomas were studied for comparison. Calretinin
      immunoreactivity was detected, at least focally, in all 10 samples of normal
      adipose tissue and in 22 of 23 lipomas or lipoma variants. Staining for
      calretinin was also positive within the lipogenic component of 28 of 29
      liposarcoma variants. Of the 7 dedifferentiated liposarcomas, 3 were focally
      positive for calretinin. Pleomorphic variants of other sarcomas, including
      undifferentiated high-grade pleomorphic sarcoma, rhabdomyosarcoma,
      leiomyosarcoma, and malignant peripheral nerve sheath tumor also exhibited focal
      calretinin immunoreactivity in a minority of cases, as did some small round cell
      sarcomas. These results suggest that calretinin immunoreactivity in normal and
      neoplastic adipose tissue is more ubiquitous than previously reported and may be
      a useful, albeit nonspecific marker of lipogenic differentiation. However, its
      utility in the differential diagnosis of fatty tumors appears limited.

PMID- 16613327
TI  - Use of whole slide imaging in surgical pathology quality assurance: design and
      pilot validation studies.
AB  - By imaging large numbers of slides automatically at high resolution, modem
      automated whole slide imaging (WSI) systems have the potential to become useful
      tools in pathology practice. This article describes a pilot validation study for
      use of automated high-speed WSI systems for surgical pathology quality assurance
      (QA). This was a retrospective comparative study in which 24 full genitourinary
      cases (including 47 surgical parts and 391 slides) were independently reviewed
      with traditional microscopy and whole slide digital images. Approximately half
      the cases had neoplasia in the diagnostic line. At the end of the study,
      diagnostic discrepancies were evaluated by a pathology consensus committee. The
      study pathologists felt that the traditional and WSI methods were comparable for
      case review. They reported no difference in perceived case complexity or
      diagnostic confidence between the methods. There were 4 clinically insignificant
      discrepancies with the signed-out cases: 2 from glass slide and 2 with WSI
      review. Of the 2 discrepancies reported by the WSI method, the committee agreed
      with the reviewer once and the original report once. At the end of the study, the
      participants agreed that automated WSI is a viable potential modality for
      surgical pathology QA, especially in multifacility health systems that would like
      to establish interfacility QA. The participants felt that major issues limiting
      the implementation of WSI-based QA did not involve image acquisition or quality
      but rather image management issues such as the pathologist's interface, the
      hospital's network, and integration with the laboratory information system.

PMID- 16613328
TI  - Aberrant composition of the dendritic cell population in hepatic lymph nodes of
      patients with hepatocellular carcinoma.
AB  - Patients with hepatocellular carcinoma (HCC) are characterized by a weak T-cell
      response to their tumor, and chronic carriers of hepatitis B virus or hepatitis C
      virus have a poor T-cell response against the virus. These inadequate T-cell
      responses may be due to insufficient activation of the T cells by dendritic cells
      (DCs). Because lymph nodes (LNs) are the primary site of antigen-specific T-cell
      activation, we hypothesized that hepatic LNs of patients with HCC and/or chronic
      viral hepatitis might have aberrant compositions of their DC populations. To
      address this hypothesis, we enumerated mature myeloid DCs (MDCs) and plasmacytoid
      DCs (PDCs) in hepatic LNs by quantitative immunohistochemistry. Patients with HCC
      and chronic viral hepatitis and patients with chronic viral hepatitis without HCC
      were compared with patients with liver inflammation of nonviral etiology and with
      organ donors with healthy livers. The numbers of PDCs and mature MDCs in hepatic
      LNs of patients with chronic viral hepatitis did not differ from those of
      patients with liver inflammation of nonviral etiology nor from individuals with
      healthy livers. However, hepatic LNs of patients with HBV or HCV infection
      complicated by HCC showed a 1.5-fold reduction in numbers of mature MDCs and a 4
      fold increase in numbers of PDCs in their T-cell areas compared with those of
      patients with viral hepatitis only (P <.01). In conclusion, patients with HCC
      have an aberrant composition of the DC population in their hepatic LNs. This may
      be one of the causes of the inadequate T-cell response against HCC in these
      patients.

PMID- 16613329
TI  - Multicystic biliary hamartoma: a hitherto undescribed lesion.
AB  - In this report, we presented 3 cases of unusual hamartomatous nodules of the
      liver. These nodules were located around hepatic capsule of the left hepatic lobe
      and characteristically protruded from the liver. Histologically, these nodular
      lesions consisted of ductal structures, periductal glands, and fibrous connective
      tissues containing blood vessels. Smooth muscle bundles focally surrounded ductal
      structures. Bile-like materials were observed within some ducts. Two cases were
      associated with xanthogranulomatous inflammation around bile-like materials, and
      this inflammatory process extended from ductal lumens to periductal connective
      tissues. In contrast, the remaining case, which was not associated with
      inflammation, showed a honeycomb appearance. Ductal epithelium and periductal
      glands resembled biliary epithelium and peribiliary glands, respectively, and
      they also expressed biliary-type cytokeratins such as cytokeratins 7 and 19.
      These nodules shared pathologic characteristics of ciliated hepatic foregut
      cysts, such as their location (around the falciform ligament) and periductal
      smooth muscle bundles, but did not fulfill the diagnostic criteria (no ciliated
      cells and multilocular lesions). These hamartomatous nodules of the liver did not
      fit into any of the described categories of hepatic nodular lesions. At present,
      we speculate that these lesions might be related to developmental abnormalities
      of the biliary tract or embryonal foregut.

PMID- 16613330
TI  - Intraprostatic spermatozoa: zonal distribution and association with atrophy.
AB  - Intraprostatic spermatozoa (IS) have been demonstrated in only 2 articles in the
      literature reporting on postmortem prostates. Intraprostatic spermatozoa have not
      been previously described in radical prostatectomies. This is the first study
      that describes the presence of IS in radical prostatectomies with prostatic
      carcinoma (PC) and its association with atrophy. We examined whole mount sagittal
      sections from 69 consecutive radical prostatectomy cases for PC. A central
      section including the seminal vesicle ejaculatory duct urethra complex (SVEDU)
      from each case was stained with Berg's stain to identify spermatozoa and their
      location. The extent and the type of atrophy were assessed on the entire prostate
      by using a grid method. Eighteen cases (26.1%) revealed spermatozoa both in the
      SVEDU and in the prostate (IS) (group 1). Twenty-two cases (31.9%) showed
      spermatozoa exclusively in the SVEDU but not in the prostate (group 2). The
      remaining 29 cases (42.0%) had no spermatozoa in either site. Location of IS was
      72.2% peripheral zone, 22.2% central zone, and 5.6% transitional zone.
      Intraprostatic spermatozoa were frequently seen accompanied by inflammatory
      infiltrate in the periglandular stroma. The extent of atrophy was greater in
      group 1 than in group 2 (25.7% versus 15.3%; P = .006). Postatrophic hyperplasia
      was seen more frequently in group 1 than in group 2 (72.2% versus 40.9%; P =
      .025). In conclusion, the frequency of IS is 26.1% when including all prostates
      and 45.0% when including prostates with evidence of residual ejaculate
      (spermatozoa in the SVEDU), more than previously reported. Intraprostatic
      spermatozoa are predominantly located in the peripheral zone similar to atrophy
      and PC. Prostates with IS have larger atrophic areas and increased frequency of
      postatrophic hyperplasia. The role of IS in the pathogenesis of prostate
      inflammation and atrophy should be investigated.

PMID- 16613331
TI  - Fibroblast activation protein: a serine protease expressed at the remodeling
      interface in idiopathic pulmonary fibrosis.
AB  - Fibroblast activation protein (FAPalpha) is a member of the cell surface
      dipeptidyl peptidase (DPP) family of serine proteases. In its dimer form,
      FAPalpha exhibits gelatinase, collagenase, and DPP activity in vitro. Reactive
      fibroblasts in healing wounds and stromal fibroblasts associated with epithelial
      tumors express FAPalpha. Idiopathic pulmonary fibrosis (IPF) is a disease of the
      lung characterized by progressive fibrosis with no clear etiology or molecular
      marker for disease activity. Recently, it has been shown that fibroblast FAPalpha
      expression is induced in liver cirrhosis, with an expression pattern distinct
      from alpha-smooth muscle actin (alpha-SMA). In this study, we determine whether
      FAPalpha expression is selectively induced in areas of ongoing tissue remodeling
      characterized by fibroblast foci in IPF. Human lung tissue was obtained from
      patients with IPF, centrilobular emphysema, and normal lung. Immunohistochemical
      studies were performed using anti-FAPalpha antibody and antibodies against alpha
      SMA and CD26 (DPPIV), another member of the DPP family. We found that FAPalpha
      was not expressed in normal human lung tissue or tissue with evidence of
      centriacinar emphysema, but was induced in all patients with IPF and With a
      pattern distinct from that of CD26 found primarily on hyperplastic alveolar
      epithelium. Specifically, FAPalpha was detected in fibroblast foci and in
      fibrotic interstitium and not in the interstitium of adjacent architecturally
      normal lung. Alveolar/airway epithelium and vascular smooth muscle did not
      express FAPalpha. This is the first report of FAPalpha expression in IPF and our
      results suggest that FAPalpha is selectively induced in fibrotic foci, but not in
      normal or emphysematous lung. Future studies will address whether FAPalpha may be
      used as a marker for disease activity in IPF.

PMID- 16613332
TI  - Contribution of microdissection for the detection of microsatellite instability
      in colorectal cancer.
AB  - The determination ofmicrosatellite instability (MSI) is an important step in the
      identification of familial colorectal cancer such as hereditary nonpolyposis
      colon cancer. It could also be of interest in the therapeutic management of
      sporadic cancer. International criteria for the determination of MSI have been
      published, recommending the use of microdissection. The aim of this work was to
      evaluate the impact of contaminant normal DNA in tumor samples for MSI assessment
      in colorectal cancer using a microdissection technique. We performed a
      comparative analysis of the microsatellite status between total DNA (DNA
      extracted from whole tumor samples) and microdissected DNA in 3 different regions
      from 23 cases of colorectal cancer. Six microsatellites were amplified using
      fluorescent polymerase chain reaction. We analyzed 9 cases with MSI and 14 cases
      without instability, with similar results between total DNA and microdissected
      DNA. Moreover, within a same tumor, the MSI phenotype was observed regardless of
      the region analyzed. Thus, this work shows the reproducibility of the MSI
      phenotype throughout a tumor. However, we observed a regional heterogeneity of
      the MSI profile, consisting of variations in the number and the size of unstable
      alleles within different regions. This result reflects the genetic heterogeneity
      of colorectal cancer with MSI. In the 14 cases without instability, we observed
      an increase of more than 60% in the loss of heterozygosity detection rate after
      microdissection. Thus, this work confirms the contribution of microdissection for
      loss of heterozygosity assessment.

PMID- 16613333
TI  - Ductal carcinoma in situ of the breast with osteoclast-like giant cells.
AB  - Mammary carcinoma with multinucleated osteoclast-like giant cells (OGCs) is a
      rare, distinctive variant of breast carcinoma. To date, all of these instances
      have been described as part of an invasive carcinoma. Here, we report a case of
      ductal carcinoma in situ of the breast with numerous admixed OGCs present within
      gland lumens without an associated invasive component. Similar to invasive
      carcinomas with OGCs, both the in situ carcinoma and the OGCs exhibited
      overexpression for vascular endothelial growth factor. This case expands the
      spectrum of tumors associated with OGCs and provides further evidence for the
      possible role of vascular endothelial growth factor in the stromal-epithelial
      interactions of in situ mammary carcinoma.

PMID- 16613335
TI  - Prostate-specific antigen: a clinical and mathematical conundrum.

PMID- 16613334
TI  - Enteropathy with loss of enteroendocrine and paneth cells in a patient with
      immune dysregulation: a case of adult autoimmune enteropathy.
AB  - Autoimmune enteropathy (AIE) is a relatively rare condition found most frequently
      in children. It presents with persistent watery diarrhea and malabsorption and
      may require total parenteral nutrition for nutritional support. Rare cases have
      been reported in adults. On histology, the small intestinal villi are flattened
      but lack the intraepithelial lymphocytosis of celiac disease. In children and
      rarely in adults, some cases are linked to the IPEX syndrome (Immune
      dysregulation, Polyendocrinopathy, Enteropathy, X-linked inheritance). We report
      a 21-year-old man who presented with chronic persistent diarrhea for 4 years. The
      duodenal biopsies showed villous blunting, chronic inflammation, and decreased to
      absent goblet cells, Paneth cells, and endocrine cells by histology and electron
      microscopy. These changes are consistent with an AIE with involvement of non
      enterocyte populations. Pathologists must be aware of the possibility of AIE in
      adults and consider it in the differential diagnosis of duodenitis,
      intraepithelial lymphocytosis, and small bowel villous flattening.

PMID- 16613336
TI  - Predictive probability of serum prostate-specific antigen for prostate cancer: an
      approach using Bayes rule.
AB  - This article introduces the use of Bayes probability rule to calculate age and
      serum prostate-specific antigen (PSA)-specific positive predictive values (PPVs)
      for prostate cancer. The PPV is the conditional probability of having prostate
      cancer, given a value of PSA and a particular age group. The formulation uses
      values of sensitivity obtained from previously reported studies of more than
      2,700 men with prostate cancer, and it uses values of specificity obtained from
      previously reported studies of more than 99,000 men without prostate cancer. The
      formulation also introduces the use of a population-based and age-specific
      probability of prostate cancer, and for this it relies on the National Cancer
      Institute-sponsored Surveillance, Epidemiology and End Results data. The Bayes
      PPV suggests that in younger men, cut points defining an elevated PSA level
      should be raised rather than lowered. The Bayes formulation also provides
      estimates of the PPV for narrow intervals of PSA, and these tabulated results may
      provide useful guidelines for the implications of serum PSA levels at specific
      age groups.

PMID- 16613337
TI  - The quality of laboratory testing today: an assessment of sigma metrics for
      analytic quality using performance data from proficiency testing surveys and the
      CLIA criteria for acceptable performance.
AB  - To assess the analytic quality of laboratory testing in the United States, we
      obtained proficiency testing survey results from several national programs that
      comply with Clinical Laboratory Improvement Amendments (CLIA) regulations. We
      studied regulated tests (cholesterol, glucose, calcium, fibrinogen, and
      prothrombin time) and nonregulated tests (international normalized ratio [INR],
      glycohemoglobin, and prostate-specific antigen [PSA]). Quality was assessed on
      the sigma scale with a benchmark for minimum process performance of 3 sigma and a
      goal for world-class quality of 6 sigma. Based on the CLIA criteria for
      acceptable performance in proficiency testing (allowable total errors [TEa]), the
      national quality of cholesterol testing (TEa = 10%) estimated sigma values as 2.9
      to 3.0; glucose (TEa = 10%), 2.9 to 3.3; calcium (TEa = 1.0 mg/dL), 2.8 to 3.0;
      prothrombin time (TEa = 15%), 1.8; INR (TEa = 20%), 2.4 to 3.5; fibrinogen (TEa =
      20%), 1.8 to 3.2; glycohemoglobin (TEa = 10%), 1.9 to 2.6; and PSA (TEa = 10%),
      1.2 to 1.8. The analytic quality of laboratory tests requires improvement in
      measurement performance and more intensive quality control monitoring than the
      CLIA minimum of 2 levels per day.

PMID- 16613338
TI  - Cholesterol crystals causing falsely elevated automated cell count.
AB  - This is a report of 3 cases of body fluid containing numerous cholesterol
      crystals that caused falsely elevated cell counts on an automated cell counter.
      Two of the cases were pleural effusion fluid from patients with long-standing
      rheumatoid arthritis. Fluid in the third case was from upper extremity cystic
      lesions of a patient with squamous cell carcinoma of the head and neck.
      Microscopic examination revealed abundant cholesterol crystals in all fluid
      samples. In all 3 cases, initially, the automated cell counter reported very
      elevated WBC and RBC counts that were much higher than those from the manual
      count. This interference by cholesterol in the automated cell counter is
      discussed. In addition, possible pathophysiology of cholesterol formation in the
      body fluid is discussed and chylous and pseudochylous (chyliform) effusions are
      reviewed. Finally, the use of automated instruments in the evaluation of body
      fluid is reviewed.

PMID- 16613339
TI  - A comparison of morphologic features, flow cytometry, TCR-Vbeta analysis, and TCR
      PCR in qualitative and quantitative assessment of peripheral blood involvement by
      Sezary syndrome.
AB  - The strengths and weaknesses of various laboratory methods for peripheral blood
      (PB) Sezary cell quantitation have not been compared rigorously. In this study,
      manual Sezary cell counting, qualitative and quantitative flow cytometry, T-cell
      receptor (TCR) Vbeta flow cytometry, and TCR polymerase chain reaction were
      performed on PB specimens from 11 patients with Sezary syndrome (SS), 9 with
      reactive erythroderma, 6 with mycosis fungoides, and 11 healthy control subjects.
      These methods identified neoplastic cells in more than 90% of SS cases. The
      diagnostic specificities of these tests varied; they were enhanced by applying
      criteria proposed by the International Society for Cutaneous Lymphoma. Comparison
      of sequentially analyzed specimens from 6 patients with SS revealed that although
      the absolute number of clonal cells was reduced, in some cases, these cells still
      constituted the vast majority of the CD4+ T-cell subset, suggesting that
      quantitative subset analysis might be sufficient to monitor changes in the PB
      tumor burden.

PMID- 16613340
TI  - E-cadherin status in breast cancer correlates with histologic type but does not
      correlate with established prognostic parameters.
AB  - Our objective was to assess the loss of E-cadherin (EC) as a diagnostic marker or
      a predictor of prognosis. We stained 276 breast carcinomas with monoclonal
      antibodies to EC (invasive lobular carcinomas [ILC] and variants, 59; invasive
      ductal carcinoma and ductal special types [IDC], 204; tubulolobular carcinoma
      [TLC], 4; and invasive carcinoma [IC], uncertain whether lobular or ductal type,
      9). The results were as follows: EC+IDCs, 99.5%; EC-ILCs, 90%; EC+ILCs, 10%;
      EC+pleomorphic ILCs, 20%; EC-ICs, 44%. All 4 TLCs showed positive tubules while
      cords were negative. Statistically a correlation of EC loss with a positive
      diagnosis of ILC was found but there was no correlation with any prognostic tumor
      variables. A negative EC stain confirms the diagnosis of ILC (specificity, 97.7%;
      negative predictive value, 96.8%; sensitivity, 88.1%; positive predictive value,
      91.2%). EC is helpful in classifying cases with indeterminate histologic
      features. EC loss is uncommon in nonlobular carcinomas with no correlation to
      currently established prognostic variables.

PMID- 16613341
TI  - HIV-1 target cells in foreskins of African men with varying histories of sexually
      transmitted infections.
AB  - Numerous epidemiologic studies have found significant associations between lack
      of circumcision and HIV-1 acquisition in men. To our knowledge, this is the first
      study of human foreskin tissue that examines biologic mechanisms that increase
      susceptibility of uncircumcised African men to HIV-1. Foreskin specimens from 20
      men with and 19 men with no history of sexually transmitted infections were
      examined for HIV-1 target cells. Most Langerhans cells were found in the
      epithelium; most CD4+ T cells and macrophages were in the submucosa. There were
      no differences in HIV-1 target cells between men with and those without history
      of sexually transmitted infections. However Langerhans cells and macrophages were
      more abundant in the group with a history of infection. The densities and
      positions of HIV-1 target cells in the foreskin tissue of these Kenyan men
      indicate that the inner mucosal surface of the human foreskin contains cells that
      make it highly susceptible to HIV infection.

PMID- 16613342
TI  - Caveolin-1 immunohistochemical analysis in differentiating chromophobe renal cell
      carcinoma from renal oncocytoma.
AB  - Chromophobe renal cell carcinoma (ChRCC) and oncocytoma might mimic each other
      histologically. We studied the immunohistochemical staining pattern of caveolin-1
      in 21 ChRCCs and 26 oncocytomas and compared it with cytokeratin (CK) 7 to
      evaluate its usefulness in differentiating these 2 neoplasms. All 21 ChRCCs
      (100%) were positive for caveolin-1, 20 of which were stained in 20% or more of
      the tumor cells. In contrast, only 3 (12%) of 26 oncocytomas showed positivity in
      fewer than 20% tumor cells and 23 (88%) of 26 were negative. In the nonneoplastic
      kidney, positive caveolin-1 staining was detected in the interstitial blood
      vessels and the parietal cells of the Bowman capsules but not in the tubular
      epithelium and glomerular and peritubular capillaries. All 21 ChRCCs (100%) were
      positive for CK7, with 18 (86%) stained in 20% or more of the tumor cells and 3
      (14%) in fewer than 20%. Of 26 oncocytomas, 25 (96%) were positive for CK7, with
      7 (27%) stained in 20% or more of the tumor cells and 18 (69%) in fewer than 20%.
      These results strongly suggest that caveolin-1 immunohistochemical analysis is
      useful for differentiating ChRCC from oncocytoma and is superior to CK7.

PMID- 16613343
TI  - Coexistent anaplastic and differentiated thyroid carcinoma: an
      immunohistochemical study.
AB  - The aim of the present study was to clarify the underlying molecules that might
      contribute to the highly aggressive behavior of anaplastic thyroid carcinoma. We
      selected 5 cases of anaplastic thyroid carcinoma that had a differentiated area
      to determine differences in the molecules of undifferentiated and differentiated
      cancer cells. We immunohistochemically examined the localization of nuclear
      antigen (Ki-67), proliferating cell nuclear antigen (PCNA), p53, apoptotic
      protease-activating factor-1 (Apaf-1), CD26, galectin-3, E-cadherin, and CD147.
      We found increased Ki-67, PCNA, and p53 labeling indices; decreased levels of
      Apaf-1, CD26, galectin-3, and E-cadherin; and overexpression of CD147 in the
      undifferentiated area compared with the differentiated area. These findings
      indicate high proliferative properties, suppression of apoptosis, disruption of
      cell-cell interaction, and induction of matrix metalloproteinases in the
      undifferentiated areas. Thus the molecules examined might be useful for
      evaluating the aggressive nature of this tumor and the prognosis.

PMID- 16613344
TI  - MIB-1 and MCM-2 immunohistochemical analysis does not aid in identification of
      serrated colorectal polyps with abnormal proliferation.
AB  - We investigated the staining characteristics of serrated polyps with abnormal
      proliferation (SPAP) using MIB-1 and MCM-2 to determine if they could provide
      assistance in delineating SPAPs from traditional hyperplastic polyps (HPs). Using
      published morphologic criteria we reviewed H&E slides of 107 polyps from 80
      patients. Thirty-nine (36.4%) polyps met the criteria for SPAP Within a given
      region, polyps in the transverse colon had the largest percentage of SPAPs
      (50.0%) followed by the right colon (40.9%). The majority of SPAPs (82.1%) and
      HPs (72.1%) showed MIB-1 staining confined to the basal third of the crypts. The
      majority of SPAPs (59.0%) and HPs (52.9%) showed MCM-2 staining extending into
      the apical third of the crypts. We do not recommend MIB-1 or MCM-2 staining to
      differentiate SPAPs from conventional HPs, since staining characteristics are not
      significantly different between the 2 groups, and frequent variable crypt
      staining within a given polyp is difficult to interpret.

PMID- 16613345
TI  - Negative colposcopic biopsy after positive human papilloma virus (HPV) DNA
      testing: false-positive HPV results or false-negative histologic findings?
AB  - We studied histologic examination-related factors contributing to false-negative
      colposcopic biopsy results. Patients positive for high-risk human papillomavirus
      (HPV) DNA with negative cervical histologic findings were identified between
      January 2002 and December 2003. Three additional H&E-stained levels were obtained
      when the original diagnosis was confirmed on review. Patients with atypical
      squamous cells of undetermined significance (ASC) Papanicolaou test results,
      positive HPV DNA results, and negative cervical histologic findings accounted for
      4.5% of all ASC smears submitted for HPV DNA testing. Slides and tissue blocks
      were available for 95 cases; 4% had focal HPV infection or mild dysplasia. When
      deeper levels were examined, 31% had clinically significant lesions: HPV
      infection or cervical intraepithelial neoplasia (CIN) 1, 19%; CIN 2/3, 8%; and
      dysplasia, not otherwise specified, 3%. Of the remaining patients, follow-up
      revealed squamous abnormalities in 25%. About 5% of patients with positive HPV
      DNA results had a negative follow-up biopsy result. "False-negative" biopsies
      accounted for one third of cases. Additional levels should be obtained for
      discrepant results. Close follow-up is crucial when the initial biopsy result is
      negative because a small number of patients will have squamous abnormalities in
      subsequent studies.

PMID- 16613346
TI  - Pulmonary artery sarcoma: a clinicopathologic and immunohistochemical study of 12
      cases.
AB  - We report 12 cases of pulmonary artery sarcoma. The mean age at diagnosis was
      48.4 years. Based on histomorphologic features and immunohistochemical findings,
      2 tumors were classified as rhabdomyosarcoma, 4 as leiomyosarcoma, 1 as
      osteogenic sarcoma, 1 as angiosarcoma, and 4 as high-grade sarcoma. All patients
      underwent surgery. In addition, 7 patients received neoadjuvant or adjuvant
      therapy. Five patients died 3 to 23 months after surgery. Three patients were
      still alive at 8, 27, and 68 months at last follow-up. Another 3 patients were
      alive at 2, 15, and 40 months and then lost to follow-up. The 2 patients with the
      longest survival (40 months and 68 months) had a diagnosis of leiomyosarcoma.
      Both patients with rhabdomyosarcoma died at 3 months after surgery. Pulmonary
      artery sarcoma is an uncommon entity with a poor prognosis. The role of early
      diagnosis, histologic classification, surgical treatment, and adjuvant therapy in
      patient outcome is discussed.

PMID- 16613347
TI  - Prognostic significance of p53 and Ki-67 antigen expression in surgically treated
      non-small cell lung cancer: immunocytochemical detection with imprint cytology.
AB  - The purpose of this study was to determine the prognostic significance of the
      expression of p53 and Ki-67 in non-small cell lung cancer (NSCLC) using
      immunocytochemical detection. All consecutive NSCLC cases were selected for
      study, and, after surgery, a part of each tumor sample was frozen at -20 degrees
      C and stored for immunocytochemical studies. Overexpression of p53 was associated
      significantly with worse patient outcome in stage I disease, whereas no excess
      risk was evident in stage II and III cases. The same pattern was observed for Ki
      67 expression. The excess risk in stage I cases with p53 and Ki-67 overexpression
      was observed only in adenocarcinoma. These findings are in agreement with other
      retrospective studies and support the hypothesis that p53 alteration may have
      different roles in adenocarcinoma and in squamous cell carcinoma, such as a
      carcinogenic factor for both cellular types but progression only for
      adenocarcinoma.

PMID- 16613348
TI  - Lymphocytic esophagitis: a histologic subset of chronic esophagitis.
AB  - A novel histologic phenotype of chronic esophagitis, ie, lymphocytic esophagitis,
      is reported in 20 patients. Lymphocytic esophagitis is characterized by high
      numbers of intraepithelial lymphocytes (IELs) gathered mainly around
      peripapillary fields and by none (n = 12) to occasional (n = 8) CD15+
      intraepithelial granulocytes. IELs expressed CD3, CD4 (42%), CD8 (36%), and
      granzyme B (0.2%), whereas T-cell intracytoplasmic antigen (TIA) 1 was not
      expressed. Of the 20 patients, 11 (55%) were 17 years or younger. Of 20 patients,
      5 had no symptoms in the upper gastrointestinal tract. Only 4 (20%) of 20
      patients had symptoms of gastroesophageal reflux disease and 6 (30%) of
      gastroduodenitis; 2 (10%) had celiac disease; 4 (20%) had carcinoma of the
      esophagus (1) or elsewhere (3); 1 (5%) each had hiatus hernia, gastric
      ulcer/asthma/blood hypertension, Hashimoto thyroiditis, and cirrhosis/diabetes;
      and 8 (40%) had Crohn disease. Hence, a novel histologic phenotype of chronic
      esophagitis called lymphocytic esophagitis is reported. Because phenotype is
      defined as the visible features resulting from the interaction between the
      genetic makeup and the environment, it is suggested that those factors might have
      a decisive role in the development of lymphocytic esophagitis.

PMID- 16613349
TI  - Transthoracic fine-needle aspiration vs concurrent core needle biopsy in
      diagnosis of intrathoracic lesions: a retrospective comparison of diagnostic
      accuracy.
AB  - To assess the value and limitations of fine-needle aspiration (FNA) and core
      needle biopsy (CNB) in the diagnosis of intrathoracic lesions, we retrospectively
      compared the diagnostic accuracy of 362 FNA and concurrent CNB procedures
      performed on 350 patients. Based on the final diagnoses that were determined
      based on combined information from biopsy, resection, clinical, radiologic, and
      microbiologic findings, the study cases were grouped into 188 malignant, 161
      benign, and 13 inconclusive lesions. FNA and CNB yielded similar diagnostic
      accuracy for malignant tumors (85.1% vs 86.7%) and epithelial malignant neoplasms
      (86.4% vs 85.2%), whereas CNB yielded better diagnostic accuracy (96%) than FNA
      (77%) for nonepithelial malignant neoplasms. Combined FNA and CNB substantially
      improved the rate of malignancy diagnosis (95.2%). Of 161 benign cases, 50 were
      proven to be benign-specific lesions; FNA provided specific diagnosis in 20 (40%)
      and CNB in 46 (92%). The remaining 111 benign lesions yielded benign-nonspecific
      findings on both specimens. These results indicate that CNB should be obtained
      when clinical or radiologic findings do not match the cytologic findings or
      nonepithelial lesions and benign lesions are considered likely.

PMID- 16613350
TI  - Anti-glomerular basement membrane glomerulonephritis: a morphologic study of 80
      cases.
AB  - Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare disease
      caused by IgG autoantibodies against the glomerular basement membrane. We
      describe clinical and pathologic findings in a series of renal biopsy specimens
      from 80 patients. The patients ranged in age from 16 to 87 years. The age
      distribution was bimodal, with one peak at a young age predominated by males and
      a second peak in the sixth to eighth decades with females predominating. Most
      patients (70 [88%]) had severe necrotizing glomerulonephritis with crescents in
      more that 50% of glomeruli. The fraction of crescentic glomeruli in biopsy
      specimens correlated well with serum creatinine levels but not with serologic
      titers for anti-GBM antibodies. Interstitial fibrosis was uncommon and, when
      present, minimal to mild. Linear IgG deposition defines this entity, but
      immunofluorescent costaining for other immunoglobulins and complement is found
      frequently. To our knowledge, this is the largest series of renal biopsy
      specimens with anti-GBM glomerulonephritis studied to date.

PMID- 16613351
TI  - NK- and B-cell infiltration correlates with worse outcome in metastatic ovarian
      carcinoma.
AB  - We studied the clinical role of leukocyte infiltration and chemokine receptor
      expression in ovarian carcinoma effusions. Expression of leukocyte markers (CD3,
      CD4, CD8, CD4/CD8 ratio, CD16, CD19, and CD14) and chemokine receptors (CXCR1,
      CXCR4, CCR2, CCR5, and CCR7) was studied in 73 effusions by using flow cytometry.
      CXCR4, CCR5, and CCR7 were expressed abundantly on leukocytes, but all receptors
      were expressed rarely on cancer cells. The presence of natural killer cells (P =
      .042) and International Federation of Gynecology and Obstetrics (FIGO) stage IV
      disease (P = .024) predicted worse overall survival (OS). A higher percentage of
      CD19+ cells (P = .015) and stage IV disease (P = .008) predicted poor survival
      for patients with postchemotherapy effusions. Only FIGO stage retained
      significance as a predictor of OS (P = .035) in multivariate analysis. Chemokine
      receptors are expressed widely on leukocytes but rarely on carcinoma cells in
      ovarian carcinoma effusions, arguing against an autocrine chemokine pathway in
      this malignancy. Immune response parameters in ovarian cancer effusions are weak
      predictors of outcome.

PMID- 16613352
TI  - Comparison of complement fixation with two enzyme-linked immunosorbent assays for
      the detection of antibodies to respiratory viral antigens.
AB  - We compared complement fixation (CF) for the measurement of antibodies against
      influenza A, influenza B, respiratory syncytial virus (RSV), human adenovirus,
      and parainfluenza viruses 1, 2, and 3 (para-1, para-2, and para-3) with 2 enzyme
      linked immunosorbent assays (ELISA kits, A and B). The IgG ELISA kits compared
      very well with each other except for the influenza A and B IgG ELISAs. The IgG
      ELISAs, in general, did not agree with CF In contrast, the IgM ELISAs compared
      well with CF and each other except for the consensus parainfluenza panel from
      ELISA B. The poor agreement of the IgG ELISAs with the CF test can be explained
      by the increased sensitivity of the ELISAs and differences between CF antigens
      and the ELISA antigens. The influenza A and influenza B ELISA antigens differed
      between both kits, which may explain their poor agreement. The ELISA is a
      suitable replacement for CF, providing greater sensitivity, isotype specificity,
      and ease of use.

PMID- 16613353
TI  - Evaluation of an in vitro assay for interferon gamma production in response to
      the Mycobacterium tuberculosis-synthesized peptide antigens ESAT-6 and CFP-10 and
      the PPD skin test.
AB  - We compared the tuberculin skin test (TST) to QuantiFERON-TB (QFT) and
      QuantiFERON-TB Gold (QFT-G) for the detection of latent tuberculosis. The QFT-G
      uses synthesized early secretory antigenic target 6 and culture filtrate protein
      10 peptide antigens instead of purified protein derivative (PPD) antigens. The
      study included 137 adults in 3 groups: 1 (n = 81), at low risk for Mycobacterium
      tuberculosis (TB) and not vaccinated for Mycobacterium bovis bacillus Calmette
      Guerin (BCG); 2 (n = 30), probably had TB exposure and were BCG vaccinated; and 3
      (n = 26), at low risk for TB, not BCG vaccinated, but previously had a positive
      TST result. Positive results were as follows: group 1: TST 3 (3.7%); QFT 9
      (11.1%); and QFT-G, 0 (0.0%); group 2: TST 26 (86.7%); QFT, 15 (50.0%); and QFT
      G, 5 (16. 7%); and group 3: TST, 26 (100.0%); QFT, 13 (50.0%); and QFT-G, 9
      (34.6%). The QFT-G demonstrated less cross-reactivity with BCG antigen and was
      more specific than QFT and TST in low-risk individuals.

PMID- 16613354
TI  - The potency of prevalence.

PMID- 16613355
TI  - Improving healthcare. A dose of competition.

PMID- 16613356
TI  - Payment philosophy: make a market.

PMID- 16613357
TI  - Sausages and surveys.

PMID- 16613358
TI  - 1918 the influenza pandemic.

PMID- 16613359
TI  - Influenza facts.

PMID- 16613360
TI  - Introduction: avian flu.

PMID- 16613361
TI  - Vaccines to protect humans from pandemic avian influenza strains.
AB  - Influenza viruses infect a wide range of animal hosts and cause yearly wintertime
      epidemics among people living in temperate zones. Because of their ability to
      mutate, re-assort gene segments, and cross species, influenza viruses can also
      lead to pandemics in which immunologically naive people are exposed to a new,
      highly contagious subtype. In the last century, these pandemics were caused by
      influenza viruses whose surface attachment proteins, or hemagglutinins, were
      derived from birds, the natural reservoir of influenza virus. Vaccines are the
      primary means to provide protection for people at risk for inter-pandemic
      influenza, and new vaccines, directed against avian-potentially pandemic-strains
      are now being tested. To date, these vaccines have been shown to be safe and well
      tolerated, but have required multiple doses and dosage levels higher than
      traditionally needed for seasonal influenza vaccines in order to generate immune
      responses thought to be protective. No efficacy studies have yet been performed.
      Future efforts will be directed toward adjuvants, different routes of
      administration, newer manufacturing methods, and possibly new viral targets.

PMID- 16613362
TI  - Quarantine and isolation.

PMID- 16613363
TI  - Mandatory influenza vaccination for health care workers--a timely step forward.

PMID- 16613364
TI  - Influenza vaccine availability in the private practice setting in Maryland.

PMID- 16613365
TI  - Influenza pandemic: the need to plan ahead.

PMID- 16613366
TI  - Influenza.

PMID- 16613367
TI  - [Assessment of voice acoustic parameters in female teachers with diagnosed
      occupational voice disorders].
AB  - BACKGROUND: Laryngovideostroboscopy is the method most frequently used in the
      assessment of voice disorders. However, the employment of quantitative methods,
      such as voice acoustic analysis, is essential for evaluating the effectiveness of
      prophylactic and therapeutic activities as well as for objective medical
      certification of larynx pathologies. The aim of this study was to examine voice
      acoustic parameters in female teachers with occupational voice diseases.
      MATERIALS AND METHODS: Acoustic analysis (IRIS software) was performed in 66
      female teachers, including 35 teachers with occupational voice diseases and 31
      with functional dysphonia. RESULTS: The teachers with occupational voice diseases
      presented the lower average fundamental frequency (193 Hz) compared to the group
      with functional dysphonia (209 Hz) and to the normative value (236 Hz), whereas
      other acoustic parameters did not differ significantly in both groups.
      CONCLUSIONS: Voice acoustic analysis, when applied separately from vocal loading,
      cannot be used as a testing method to verify the diagnosis of occupational voice
      disorders.

PMID- 16613368
TI  - [Evaluation of the intensity of stress at work and burnout syndrome in the
      managers].
AB  - BACKGROUND: Burn out syndrome is connected with the intensity of stress at work.
      It is a common problem among people who work in management departments. This
      significantly decreased the effectiveness of work and the quality of psychosocial
      functioning. The purpose of the study was to establish the dependence between
      occupational stress and burnout syndrome in the group of managers. MATERIAL AND
      METHODS: The studied group consisted of 73 managers, aged 27-55 years. The
      Perceived Job Stress Questionnaire and Maslach Burnout Inventory (MBI) were used
      in this study. RESULTS: The data obtained revealed significant intensity of
      stress filling at work in evaluated group. The most stressful factors occur:
      psychical balance of work, lack of rewards, social contacts and uncertainty at
      work. The highest risk of burnout syndrome is associated with symptoms of
      emotional exhaustion and depersonalization. CONCLUSIONS: Higher intensity of
      occupational stress is connected with the greater intensification of burnout
      syndrome in investigated group of managers.

PMID- 16613370
TI  - [Comparative analysis of occupational hearing loss risk among private farmers
      with reference to decision-making criteria contained in the cabinet ordinances
      (current and previous)].
AB  - BACKGROUND: Noise present in the agricultural environment constitutes a
      significant risk for the hearing organ among private farmers. The change of the
      principles concerning diagnostic and decision-making procedures give rise to
      specific consequences of an ethical, social, medical, economic or political
      nature. The aim of the study was to perform a comparative analysis of the
      occurrence of the occupational hearing loss risk among private farmers, with
      reference to two different decision-making criteria. MATERIALS AND METHODS: The
      assessment of the state of hearing in farmers, previously carried out in a
      selected group of 128 people, was the major research material. A comparative
      analysis of hearing loss and the evaluation of the risk of occupational hearing
      impairment was conducted on the basis of two different decision-making criteria
      set forth in the Cabinet Ordinances of 2002 and 1983, supplemented with the
      Instruction of the Minister of Health issued in 1987. In the evaluation of
      hearing loss the following aspects were considered: selected age and employment
      duration intervals as well as selected audiometric frequencies and types of the
      diagnosed hearing loss (total or corrected). The analysis of occupational risk,
      however, was based on specified frequencies of standard-exceeding hearing loss
      (standard: 30 dB or 45 dB). RESULTS: The analysis showed that the total hearing
      loss increased with farmers' age, whereas corrected loss was not age-ndependent.
      An increase in hearing loss independent on the duration of employment was
      observed only up to 30 years of employment; beyond this period a decrease in
      hearing loss (total and corrected) was noted. Standard-exceeding hearing loss,
      according to the 1983 decision-making criterion occurred considerably more often
      (11 cases; 8.6%), compared to that based on the 2002 criterion (8 cases; 6.2%).
      CONCLUSIONS: Bearing in mind that the greater corrected hearing loss occurs among
      younger people, it is recommended to apply corrected hearing loss in the
      evaluation of the degree of hearing impairment. Due to more frequent hearing loss
      within the range of high frequencies (4 and 6 kHz), and to provide the required
      distinctiveness of speech (tone), the frequency of 4 kHz should be applied in
      calculations of mean values. The comparative analysis of hearing loss inclined us
      to presume that the 1983 diagnostic procedures and decision-making criterion
      (corrected values; frequencies: 1, 2 and 4 kHz, standard: 30 dB) should be
      reinstated to ensure a proper protection of workers against noise.

PMID- 16613369
TI  - ["My work"--adaptation to work questionnaire].
AB  - BACKGROUND: Although the interest in the problem of adaptation to work among
      psychologists is still growing, there are a few methods for investigating this
      issue. The present study was undertaken to develop a new instrument for assessing
      one's adaptation to work and to evaluate the psychometric parameters of the test.
      MATERIALS AND METHODS: A questionnaire called "My work", based on the person
      environment fit theory model, has been elaborated. RESULTS: The questionnaire
      consists of 23 items, describing various aspects of adaptation to work. The
      results of a survey, performed on 292 individuals, provided the grounds for
      testing the validation parameters of the questionnaire. The following
      psychometric properties were assessed: Cronbach's alpha reliability coefficient
      (0.92), stability (0.75), and content validity. Preliminary normative values for
      the test were also established. CONCLUSIONS: The "My work" test shows a good
      psychometric characteristic and it can be useful for both research work and
      practical application (as a diagnostic tool).

PMID- 16613371
TI  - [Exposure to hazardous chemical substances in furniture industry].
AB  - BACKGROUND: The aim of the study was to assess the exposure to organic solvents
      in plants of the furniture industry. MATERIALS AND METHODS: Studies were
      conducted in five furniture plants. Hazardous chemicals present in the air at
      workposts were determined by capillary gas chromatography with mass spectrometry
      and flame ionization detection. RESULTS: The analysis of air samples collected at
      the workposts allowed to identify the following chemicals occurring during
      varnishing and cleaning of furniture surface elements: acetone, butan-2-one,
      ethyl, isobutyl and methoxypropyl acetate, 4-methylpentan-2-on, toluene,
      ethylbenzene and xylenes. Indices characteristic of combined exposure ranged from
      0.13 to 1.67 and exceeded the limit value at 21% of workposts. CONCLUSIONS: The
      results of the study indicate that chemicals present at representative workposts
      during the furniture production are harmful to health of workers, especially
      those involved in varnishing and cleaning of furniture elements.

PMID- 16613372
TI  - [How to measure efficiency of health investments in enterprises: selected
      issues].
AB  - BACKGROUND: World trends and international organization recommendations point out
      the necessity of OHS economic appraisal methods improvement in order to ensure
      effective resources management in companies. MATERIALS AND METHODS: Published
      world literature on economic appraisal results, recommendations of international
      organizations, results of the own studies on economic appraisal in the field of
      health and safety at work in the companies in Poland were the background of the
      economic appraisal model for Polish companies. Several project assumptions have
      been adopted. The model of the return of the investment, model based on the
      company participation and some elements of the net costs formula are recommended
      for Polish companies in order to appraise efficiency of the health investment.
      The basic ratio in economic evaluation should be cost/benefit ratio. The project
      of the economic evaluation algorithm has been elaborated. RESULTS AND
      CONCLUSIONS: The economic analysis of the health protection and safety at work
      should include clear division between the internal and external costs. The
      proposed model could be used for the companies management needs in two
      directions: to microeconomic efficiency appraisal of investment in
      programs/intervensions in health and safety at workplace and to analyze the
      influence of the costs of accidents and occupational diseases and costs of
      preventive programs on finance management on the company level.

PMID- 16613373
TI  - [Occupational alergy: a major health hazard among food processing workers].
AB  - Food-processing is one of the industries characterized by high exposure to
      occupational allergens. Exposure to allergens of plant or animal origin is most
      extensive during food processing, including meat, fish, fruit, vegetables, dairy
      products, and grain products as well as during production of animal feed and
      other foodstuffs. Respiratory diseases are the major problem in the food
      processing industry. It is essential to better recognize the structure of food
      allergens and mechanisms by which they induce diseases to identify risk factors
      and health problems which may occur in workers. The authors describe the most
      essential food allergens responsible for occupational diseases, reactions
      resulting from exposure to food allergens in the occupational context, their
      diagnosis and prevention in food processing workers.

PMID- 16613374
TI  - [Diagnostics of occupational asthma: measurements of exhaled nitric oxide].
AB  - Nitric oxide (NO) is an endogenous, soluble gas whose highly reactive molecules
      are involved in many biological and pathophysiological organic processes. It is
      generated from arginine through the action of the enzyme nitric oxide synthase
      (NOS). Over the recent years, accurate and non-invasive diagnostic methods have
      been searched for illustrating the allergic airway inflammation. Lately, great
      hopes have been associated with the use of measurements of exhaled nitric oxide
      (FENO) in the estimation of bronchial inflammation in asthmatic subjects. This
      method is non-invasive and can be frequently repeated. Furthermore, positive
      correlation between FENO and blood eosinophilia and induced sputum in atopic
      children and asthmatic adults has been observed. A significant increase in FENO
      after specific challenge test has also been shown. Therefore, determination of
      this parameter can be an additional source of information useful in the
      interpretation of occupational challenge tests in cases with boderline functional
      changes.

PMID- 16613375
TI  - [Epidemiology of viral hepatitis cases, types B and C, transmitted from carriers-
      health service workers to patients. Is it still a"no problem" issue in Poland].
AB  - This paper presents current epidemiological data on transmissions of HBV and HCV
      from infected health care workers to patients. In view of the increasing risk of
      those transmissions, in many countries, relevant legal regulations have been
      adopted to limit occupational activity of infected health care workers. In
      Poland, there is a real risk of such accidents (especially regarding HCV).
      Therefore, this problem should also be regulated by law in our country.

PMID- 16613376
TI  - [The influence of lead on testis function].
AB  - The deterioration of male fertility, found in numerous epidemiological studies of
      past decades, can be connected to growing exposure to environmental toxins. Heavy
      metals, especially lead is widely spread and extremely toxic. The mechanism by
      which lead exerts toxic effects on testis is quite complex. It involves
      spermatogenesis, steroidogenesis, and red-ox system. The chronic lead exposure
      can induce functional disorder (decrease of testosterone synthesis) or
      morphological disorder (decrease of testicular weight and seminal vesicle,
      peritubular fibrosis, seminiferous tubular diameter decrease and decrease in germ
      cell population related to an apoptotic process). Currently existing
      environmental and occupational exposure to lead and increasing combined exposure
      to environmental toxins results in constantly increasing number of diagnosed
      fertility impairments.

PMID- 16613377
TI  - [Verification of Polish regulations of maximum permissible intensities in
      electromagnetic fields by the Commission for Bioelectromagnetic Issues of the
      Polish Radiation Research Society].
AB  - Experts in the field of bioelectromagnetism have reported a growing need to
      verify Polish regulations on the protection against electromagnetic fields (EMF)
      in the 0-300 GHz range, especially in their maximal permissible intensities
      (MPI). There is a general belief that Polish standards do not fully comply with
      recommendations and directives of the European Union (EU) and that Polish
      regulations on the border values for environmental and occupational exposure to
      EMF are not harmonized. To this end, the Commission for Bioelectromagnetic Issues
      have been set up in the Polish Radiation Research Society. Following a through
      analysis of standards binding in Poland and EU, the Commission set about working
      on verified MPI values for EMF. This paper presents some comments of the
      Commission members, stressing the complexity of this undertaking.

PMID- 16613378
TI  - [Professor Julian Liniecki--fifty years of his professional activities and
      accomplishments].

PMID- 16613379
TI  - [International Symposium on Epidemiology in Occupational Health (EPICOH, 11-14
      September 2005, Bergen, Norway].

PMID- 16613380
TI  - [Strategies for competence development in different levels of nursing education
      according to teacher's indication].
AB  - Qualitative study carried out with twenty-two professors of public universities
      using semi-structured questionnaries for data collection. The study aimed at
      identifying the teaching strategies adopted by professors to build student
      competences in different levels of nursing education. The content analysis
      exposed the tendency in adopting a constructivist model and the intention of
      promoting pedagogical changes in the search for a different educational formation
      according to the level of complexity.

PMID- 16613381
TI  - [Managerial strategies in the implantation of family health program].
AB  - Study that focuses on the implementation process of Family Health Program (FHP)
      in a community of Santa Cruz, district of Rio de Janeiro city. This community is
      characterized by a high social and sanitary risk marked by violence. The
      objectives were: (1) to identify strategies used by local managers in the
      implantation of eight teams of FHP in this community; (2) to describe the
      mechanism of community participation in the implantation process and, (3) to
      analyse the nurse's insertion in as this process coordinator. Among these
      findings, the importance of social control is emphasized at legitimation process
      that FHP strategy causes to users, the nurse's management function to construct
      the local autonomy and approaches used by the management to introduce FHP in
      poverty communities.

PMID- 16613382
TI  - [Correlation of basic conditioning factors for selfcare of patients who underwent
      coronary bypass].
AB  - It was aimed at to correlate selfcare actions developed by patients that
      undergone coronary bypass with the variables: gender, age, occupation, marital
      status and family antecedents for cardiovascular diseases. Exploratory
      descriptive study, carried out at a cardiology hospital, in Fortaleza-CE, with 52
      patients that had undergone coronary bypass in a period less than one year. The
      patients'has the following profile: majority was men (53.84%), age from 65 years
      old or more (59.61%), retired (71.15%), married (63.46%), with family
      predisposition for cardiovascular diseases (67.30%). Women, elderly patients,
      married patients and the ones who have family predisposition for cardiovascular
      alterations had better selfcare practices, mainly when the patient is retired.
      The conclusion is that patients that participated in this research, keep a
      satisfactory selfcare level, supporting the importance of the group orientation
      process, in a continuous way and with different approaches to provide conditions
      to the patient who have been submitted to the coronary bypass to practice the
      selfcare.

PMID- 16613383
TI  - [Follow-up group for schizophrenic patients using Clozapine and their relatives:
      the participants' perception].
AB  - This study described the views of Schizophrenic patients as well as those of
      their relatives concerning the group follow-up. The population consisted of 11
      patients participating in the group and of 11 relatives who most often
      accompanied them to group meetings. Interviews, which were tape-recorded and
      fully transcribed, were used for data collection. The obtained results showed
      that the group consisted in a favorable space for talking and listening about the
      disease as well as to exchange experiences as it provided more security and self
      esteem to the participants. In addition to improving the patients' relationships
      and providing therapeutic help to their relatives. Such results showed the need
      for a new way to view mentally ill patients in order to search for more adequate
      therapeutic attitudes which can act on life production.

PMID- 16613384
TI  - [Characteristics, frequency and factors present in nipples damage occurence in
      lactating women].
AB  - Our objectives were to verify the occurrence of nipple damage, according to the
      newborn and mother characteristics; to characterize the suction pattern of
      newborn, whose mothers present nipple damage. The sample was of 1020 lactating
      women and their infants, and of them, 84 were followed up by the researcher. It
      was verified that the gestational age of the newborn, the skin color, parity and
      the type of anesthesia received by the mothers during the labor were
      statistically significant for the occurrence of nipple damage. Only 5.95% of the
      newborn revealed appropriate grasp and dynamic suction, increasing to 43.33% at
      the first appointment after hospital discharge. The most of women presented
      complete healing of lesion from 5 to 6 days postpartum, this indicate that this
      period of a week is critical, when the mother needs stimulation and follow-up to
      the maintainance of lactation.

PMID- 16613385
TI  - [Profile of adolescent suicide attempters admitted in an emergency unit].
AB  - Emergency Units frequently assist suicide attempts. It is important to study this
      phenomenon in adolescence, since this is a conflict period. This study aimed to
      outline an epidemiological profile of adolescents admitted in an Emergency Unit,
      who were diagnosed as suicide attempters. Thus, we examined the records of
      adolescents admitted at this Unit as suicide attempters in 2002. The results
      revealed that 77.8% of the cases are characterized as follows: female,
      predominant age range between 15 and 19 years old, single, white, student, living
      in neighborhoods with low purchasing power, taking medication during the day. Our
      findings were similar to those described in other studies and thus require
      special attention.

PMID- 16613386
TI  - [Quality of life and measure of disease in elderly people with end-stage renal
      disease].
AB  - The purpose of this research was to identify, in an elderly population with end
      stage renal disease (ESRD) undergoing ambulatory hemodialysis, the correlation
      between a generic index of quality of life (WHOQOL-BREF) and the severity index
      of the ESRD-SI. The work consisted of a correlational cross-section study
      conducted at two clinics providing replacement of renal therapy and involved 100
      elderly patients suffering from ESRD, who had already been in hemodialytic
      treatment for at least six months. The WHOQOL-BREF showed a negative correlation
      with the severity of the ESRD-SI and the technique employed allowed for a
      distinction to be made between patients with greater and lesser severity of ERSD
      SI.

PMID- 16613387
TI  - [The stress of the multiprofessional team in the operating room].
AB  - This article is a case study that presents common stressors, answers to
      professional's individual and collective handling in the operating room. The data
      was collected through interview of 32 persons of the surgical team, submitted to
      content analysis, arising eight differentiated categories from them: significant
      stress experiences; stressing situations; individual behavior in the operating
      room; stress handling; responsibilities and compromises; behavioral responses.
      Even though relationship with patients generates important life experiences, the
      patient was considered the minor stressor agent, being the interpersonal
      relations the most significant one. To cope with stressful situations the
      professionals use the handling focused on the problem, on emotion, on relief
      maneuvers, and on development of social relationships.

PMID- 16613388
TI  - [Institution of nurse's leadership in health matters].
AB  - The subject matter in focus in this research was the fact of nurses begin to work
      in the management leadership at the Municipal Health Foundation of Niteroi (FMS).
      The Institutional Analysis, Rene Lourau trend, was the method used for analyzing
      the relationships established by 10 nurses acting as health managers. The
      "theoretical base" was constructed by oral activity of the agents, through an
      oriented interview, limiting three categories: "The Challenge of Being a
      Manager", "The Challenge of Being a Leader" and "The Challenge of Decision
      Making". Among the knowledge constructed one can points out the CHALLENGES that
      the nurse has to face in the health management, which are: to organize the work
      of other professionals and to take charge in fact of the leader role in the
      health system.

PMID- 16613389
TI  - [Nurse's care practice according to the view of the healthcare team].
AB  - This study aims to comprehend the healthcare team perception about the
      (in)visibility of care practice of being a nurse in pediatric critical care
      units, according to Paterson and Zderad Humanist Theory. This is a qualitative
      research that combines the phenomenological approach. For data collection, it was
      used semi-structured interviews with nurses, physicians, psichologists,
      physiotherapists, nurse aides and hygienization employes working in pediatric
      critical care units of a hospital in Curitiba. The analysis followed the steps
      proposed by Giorgi and presented six categories, being three related to nurses'
      perception and three related to the multiprofessional team. Based on these
      statements it was possible to outline a conceptual model of nurses' perception
      about invisibility in their care practice, and also showed ways to obtain nurses'
      visibility.

PMID- 16613390
TI  - [An instrument for attitude measurement about professional appraisal].
AB  - The study describes a construction of an attitude measurement tool, the Likert
      Scale, about the performance evaluation process used by the Nursing Department of
      the University Hospital at University of Sao Paulo, related to the nurse's
      beliefs, feelings and ability. The test's results of confidence, Cronbach Alpha
      and Spearman-Brown Correlation, showed that the tool is confident and appropriate
      for application in other populations.

PMID- 16613391
TI  - [Application analysis of Nursing Care Systematization according to Horta's
      Conceptual Model].
AB  - This study has as purpose to analyse the implementation of the Nursing Care
      Systematization in a private hospital in medical surgical units. Results
      evidenced that the Horta's Conceptual Model was present only in part of nursing
      hystory instrument, that the remaining phases of nursing process were not inter
      related and that there was a lack of coherence of the prescribed actions in
      relation to the patient's health condition. From the results of the study it can
      be concluded that the model used for Nursing Care Systematization is eclectic,
      not obeying therefore, only to Horta's conceptual model; the totality of the data
      had not been collected in some phases of the nursing process; there is no
      correlation of the phases in the majority of analyzed patient records; diagnostic
      and planning phases do not comprise the phases of the nursing process as proposed
      by Horta.

PMID- 16613392
TI  - [The representation of the "others" in nursing relations].
AB  - The lack of humanization between health professionals and patients are becoming
      more common. We are not ethical, but we become ethical through our behavior. The
      hereby study interviews nurses who act in the hospital departments with the
      objective to identify the representation of the "other" (patient and familiar) in
      the relationship of nursing and to understand how these relationships occur. The
      study shows a clear dichotomy between theory and practice; nurses are, in most
      cases, unsatisfied with work and the recognition of the profession; there is
      difficulty in communicating with the patient without demonstrating authority;
      recognizing the importance of the family, however still not dealing with it.

PMID- 16613393
TI  - [Exhibition of the client's body during the physical examination in the intensive
      care unit].
AB  - Descriptive study with a quanti-qualitative approach that aimed at analyzing the
      involving situations during the exhibition of the client's body in his assistance
      in the ICU, the involved people's behaviors and the consequences for the own
      ones. The data were collected together with 15 female nurses, being used the
      Critical Incident Technique. It was identified situation, behavior and
      consequence categories. It was chosen, in this study, to discuss the category
      physical evaluation due to its relevance for intensive treatment. It was
      evidenced that the patient privacy protection and respect assure the quality of
      care. The gender of the person who care emerged as a complicating factor for the
      maintenance of privacy. Both professional insecurity and inability in solving
      conflicts related to the exhibition of the client's body are perceptible, even
      predominating attitudes addressed to the protection of the client's intimacy.

PMID- 16613394
TI  - [Ways of learning in the practice of the attending nurse].
AB  - This study was carried out in a university hospital in Rio de Janeiro. Its
      objectives were to identify the ways of learning in the practice of the attending
      nurse in the hospital organization. The theoretical support was based on the
      light of Shon, Perrenoud, and Benner. This is a case study with a qualitative
      approach, developed with a semi-structured interview and a focal group. The
      content analysis was done. The results suggest that in the hospital we find two
      learning modalities: learning that uses transformation elements and the one that
      uses the reproduction. We notice that nurses alternate these models taking as a
      starting point the following variables: how long they have been working in this
      field, the work atmosphere and the personal identity.

PMID- 16613395
TI  - [Reflecting about congenital malformation].
AB  - The study consisted in a bibliographical revision about congenital malformations.
      The objectives consist of making a survey of the nursing production about the
      subject, presenting the current referring contributions related to the questions
      of congenital malformations and to propitiate a reflection for the performance of
      nursing professionals when facing this situation. As results, the revision
      located studies that had been categorized in thematic units: mother perception,
      familiar questions, monitorization project and nursing care in the specific
      anomalies. The conclusion points out that the adequate assistance to be given to
      the child with congenital malformation, demands beyond technician training,
      ability and sensitivity of the multidisciplinary team, that becomes them capable
      to perceive and to intervent in the bio-psicossocial and spiritual dimension of
      the child and the family.

PMID- 16613396
TI  - [Decubitus ulcer and nutritional status: literature review].
AB  - In order to better understand aspects related to the nutritional assessment of
      patients in risk for pressure ulcers, we reviewed the national and international
      literature indexed on Medline and LILACS bibliographic databases, from 1987 to
      2001. The aim of this research was to investigate the knowledge production on
      pressure ulcers and nutritional status, as well as to learn about the authors and
      the publication focus. We concluded that patients in risk for pressure ulcers can
      be early identified based on nutritional assessment, including biochemical data,
      anthropometric evaluation, clinical data, diet history and energetic consumption.
      The alterations are frequent in elderly patients, hospitalized patients, patients
      with a chronic disease such as a vascular cerebral accident, cancer and spinal
      cord injury.

PMID- 16613397
TI  - [Subcutaneous medication administration: agreement or controverse for nursing?].
AB  - The correct and safe medication administration, independently of the form, is
      under the responsibility of the nursing team. To this team it is necessary
      specific knowledge and abilities, as well as continuous update of the processes
      that involve such care. This article has as objective to make some considerations
      about this subject, adjusting them to the common nursing practice. For this, we
      present a literature review that approaches the main application methods used for
      subcutaneous medication. After that, we argue some aspects for professional
      improvement, so that the medication administration be satisfactory and safe in
      the caring process.

PMID- 16613398
TI  - [Education and care in nursing: passport to the learning, education, and care in
      health].
AB  - This is an essay about care and education in nursing from integrative and
      converging approaches, elucidating that the dialogical process between the
      subject who cares and the citizen-subject who is cared must occur in a problem
      maker perspective, contextualized and transversalized between the two conceptual
      worlds that involve the human relations. It shows furthermore that, to the
      professional exert the care and education, he must use a "passport" that conducts
      him to different "scales" of knowledge in a creative, aesthetical, ethical,
      political and technical approach. In which the education empowers the capacity of
      care and the use of it, capacitates him to intervent in a constructive/reflexive,
      singular/plural, dynamic/flexible way, in a given historical cultural context of
      relationships between subjects.

PMID- 16613399
TI  - [Recreation and child development: an approach in music and in nursing care].
AB  - The imaginary world is important for the comprehension and insertion of the child
      in her surrounding world. Being this way, the ludicrous nursing care arises,
      assuring an integral and careful assitance, where games, plays, songs, and dances
      are present to subsidize the care. Music and all its involving and instructing
      sonority must be highlighted, being its musicality inserted in her environment.
      The child establishes herself as to be for to interact with other and the world,
      being the playing necessary for her growth and development.

PMID- 16613400
TI  - EORTC QLQ-C15-PAL: the new standard in the assessment of health-related quality
      of life in advanced cancer?

PMID- 16613401
TI  - Defining the patient population: one of the problems for palliative care
      research.
AB  - There is a lack of clear definition and clear inclusion criteria in palliative
      care research. The aim of this study was to describe consequences of three
      inclusion criteria in the build up of different study populations, studied in
      terms of size, number of doctor-patient contacts and demographic characteristics.
      General practitioners received a questionnaire for all patients who died during
      the second Dutch National Survey of General Practice (n=2194), to determine
      whether (1) patients received non-curative treatment; (2) patients received
      palliative care; and (3) death was expected (total response rate =73%). The
      criterion 'death was expected' included most patients (62%) followed by
      'palliative care' (46%) and 'noncurative treatment' (39%). Similarity between the
      definition-based populations was fair to moderate. More 'palliative care' and
      'death was expected' in patients who had cancer than 'non-curative treatment'
      patients. The conclusions show substantial differences in populations according
      to the different inclusion criteria used to select them. Future research in
      palliative care should acknowledge the limitations of using certain inclusion
      criteria and explore potential bias.

PMID- 16613402
TI  - Management guidelines for motor neurone disease patients on non-invasive
      ventilation at home.
AB  - Most motor neurone disease (MND) patients die of respiratory system
      complications. When patients have advanced disease with symptoms of respiratory
      failure, management issues can become complicated by the introduction of assisted
      ventilatory devices. Therefore, care provision by a multidisciplinary team must
      be structured and co-ordinated in order to ensure that patients and their carers
      receive the optimal level of care. The objective of this article is to review the
      literature and explore the complex issues surrounding the use of non-invasive
      positive pressure ventilation (NIPPV) in home care MND patients as a
      justification for the development of a management guideline for medical
      practitioners. A guideline for multidisciplinary care of home ventilated MND
      patients will be proposed.

PMID- 16613403
TI  - Shelter-based palliative care for the homeless terminally ill.
AB  - BACKGROUND: The homeless have high rates of mortality, but live in environments
      not conducive to terminal care. Traditional palliative care hospitals may be
      reluctant to accept such patients, due to behavior or lifestyle concerns. The
      Ottawa Inner City Health Project (OICHP) is a pilot study to improve health care
      delivery to homeless adults. This is a retrospective analysis of a cohort of
      terminally ill homeless individuals and the effectiveness of shelter-based
      palliative care. As proof of principle, a cost comparison was performed. METHODS:
      28 consecutive homeless terminally ill patients were admitted and died at a
      shelter-based palliative care hospice. Demographics, diagnoses at admission and
      course were recorded. Burden of illness was assessed by medical and psychiatric
      diagnoses, addictions, Karnofsky scale and symptom management. An expert panel
      was convened to identify alternate care locations. Using standard costing scales,
      direct versus alternate care costs were compared. RESULTS: 28 patients had a mean
      age 49 years; average length of stay 120 days. DIAGNOSES: liver disease 43%,
      HIV/AIDS 25%, malignancy 25% and other 8%. Addiction to drugs or alcohol and
      mental illness in 82% of patients. Karnofsky performance score mean 40 +/- 16.8.
      Pain management with continuous opiates in 71%. The majority reunited with
      family. Compared to alternate care locations, the hospice projected 1.39 million
      dollars savings for the patients described. CONCLUSION: The homeless terminally
      ill have a heavy burden of disease including physical illness, psychiatric
      conditions and addictions. Shelter-based palliative care can provide effective
      end-of-life care to terminally ill homeless individuals at potentially
      substantial cost savings.

PMID- 16613404
TI  - Would people with Parkinson's disease benefit from palliative care?
AB  - Parkinson's disease (PD) is a chronic, progressive, degenerative disorder of the
      nervous system, causing substantial morbidity and has the capacity to shorten
      life. People with PD and their families can find the disease devastating.
      Nevertheless, this population of patients is not usually considered a group to be
      supported by palliative care specialists. But the nature of the illness and the
      challenges of managing its many physical and psychological effects raises
      questions about the potential benefits of a palliative care approach. The purpose
      of this project was to describe the experience of PD and consider the relevance
      of palliative care for this population. Semi-structured interviews were conducted
      with eight people with PD, 21 family caregivers and six health professionals.
      Five themes were developed from the data analysis: (1) emotional impact of
      diagnosis; (2) staying connected; (3) enduring financial hardship; (4) managing
      physical challenges; and (5) finding help for advanced stages. These data
      revealed that people with PD and family caregivers are confronted with similar
      issues to people with typical palliative care diagnoses, such as advanced cancer,
      and that a palliative approach may be helpful in the care of people with PD and
      their families.

PMID- 16613405
TI  - Determinants of resource utilization in four palliative care units.
AB  - OBJECTIVE: To assess resources mobilized per day and per patient receiving
      palliative care (PC) and to explain the observed cost variability. STUDY SETTING:
      We conducted a prospective study in four French PC units. STUDY DESIGN/DATA
      COLLECTION: For each patient, socio-demographic and medical data were collected
      (using a case-report form developed specifically for this purpose) and a daily
      cost for the provision of care was estimated. Three methods were used to analyse
      causal relationships. The first method was to ask the PC staff, individually and
      in group meetings, their own perception of the relationship between daily costs
      and the other variables; the remaining two methods used the data collected in the
      prospective study: correlational analysis and segmentation. The database
      contained 140 hospitalization sequences. PRINCIPAL FINDINGS: The daily cost per
      patient was, on average, Euro 434 (standard deviation: Euro 73) and ranged from
      Euro 301 to Euro 667. Beyond differences in resources between PC units in this
      study, six variables were predictive of higher costs: degree of anxiety of
      patients and/or their families; proximity of death; extreme dependence; ENT
      cancer; relatively young age of the patient; and provision of certain procedures
      (drip, syringe driver, aspiration, oxygen therapy). CONCLUSIONS: These elements
      suggest using, not a single rate to finance this type of care, but modifying this
      tariff according to the characteristics of the patients. They raise the question
      about the criteria to be used if such a step were to be taken.

PMID- 16613406
TI  - The ethics of palliative care and euthanasia: exploring common values.
AB  - The ethical underpinnings of palliative care and those of voluntary euthanasia
      and assisted suicide (VE/AS) are often viewed as opposites. In this article, we
      review the values held in common by the euthanasia legalization movement and
      palliative care providers. Outlining this common ground serves to define, with
      greater clarity, the issues on which differences do exist, and ways in which some
      open questions, which are as yet unresolved, could be approached. Open discussion
      between VE/AS legalization advocates and palliative care providers is important
      to address these open questions seriously, and to enrich the care of terminally
      ill patients by giving members of both groups access to each other's experience.

PMID- 16613407
TI  - The proposed assisted dying bill in the U.K.: a response to Lord Joffe.

PMID- 16613408
TI  - Centralized inpatient palliative care units in remote areas: an obstacle to
      future home care?

PMID- 16613409
TI  - Older adults' attitudes to death, palliative treatment and hospice care: a view
      from Singapore.

PMID- 16613410
TI  - Caring for the caregivers.

PMID- 16613411
TI  - Assessing advance care planning readiness in individuals with kidney failure.
AB  - The purpose of this study was to initiate development of an instrument to assess
      readiness of patients to discuss advance care plans. The first step of the
      development of the instrument involved the generation of a 49-item pool
      representative of the grounded theory of personal preservation (Calvin, 2004).
      The second step was to assess the content validity of the items using both a
      professional panel of four experts in end-of-life care and a patient panel of
      five persons currently being treated with hemodialysis in an inpatient setting.
      The third step was to pilot test the resultant 30-item instrument with another
      sample of 10 patients on hemodialysis. The instrument showed preliminary evidence
      of content validity (overall content validity index = 0.90) and internal
      consistency reliability of the scale (Cronbach's alpha = 0.73).

PMID- 16613412
TI  - Illness representations in patients with chronic kidney disease on maintenance
      hemodialysis.
AB  - A sample of patients with chronic kidney disease on maintenance hemodialysis
      participated in a study to explore the relationship between illness perception
      and quality of life. Illness perception was examined based on the Common-Sense
      Model of Illness as described by Leventhal. Forty-two participants completed the
      Revised Illness Perception Questionnaire (IPQ-R), the Index of Well-being (IWB)
      and a brief demographic form. All of the subscales of the IPQ-R and the IWB
      demonstrated adequate reliability (alpha levels > or = .70) except for the
      treatment control subscale (alpha = .46). More perceived consequences of kidney
      disease and higher scores on the emotional representation scale were negatively
      correlated with scores on the IWB. Future research is needed to assess the
      influence of factors such as coping strategies on illness representations and on
      well-being. Nephrology nurses are in an optimal position to identify the illness
      perceptions of patients on chronic hemodialysis and can introduce specific coping
      mechanisms to enhance overall well-being. As well nephrology nurses can function
      as part of the overall health care team to identify the resources available to
      minimize the perceived consequences of chronic kidney disease.

PMID- 16613413
TI  - How a dedicated vascular access center can promote increased use of fistulas.
AB  - Fistula First, now a CMS "Breakthrough Initiative", sets the eventual goal of 66%
      prevalence of arteriovenous (AV) fistulas in the U.S. dialysis population. The
      benefit of an AVfistula as the hemodialysis access has been clearly demonstrated;
      yet the current incidence of AV fistulas in patients new to dialysis in the U.S.
      is extremely low and prevalence rates are approximately half the eventual target
      rate. In this article, the components of an Integrated Vascular Access Program
      are described. One of these is a dedicated Vascular Access Center (VAC), a
      facility specializing in radiographic and interventional procedures for the
      vascular access care of patients with ESRD. Procedures carried out in a dedicated
      VAC are described and are shown to support both K/DOQI and the Fistula First
      "Change Package" in terms of promoting increased prevalence of AV fistulas. These
      include preoperative vessel mapping, fistula maturation, fistula maintenance, and
      identification of candidates for secondary fistula. The above type procedures
      that were carried out in our dedicated VAC in 2004 are described. These included
      vessel mapping (n=220), fistula maturation procedures (n=104), and fistula
      maintenance procedures (n=103). The results suggest that the shift to a "fistula
      culture" within a dialysis practice requires a significant number of
      interventional procedures--both maturation and maintenance types. A dedicated VAC
      can efficiently carry out these procedures and is an important component of an
      Integrated Vascular Access Program.

PMID- 16613415
TI  - Erythropoietin claims monitoring policy: implications for clinical practice.
AB  - The revised erythropoietin claims monitoring policy that will govern
      reimbursement by the Centers for Medicare & Medicaid Services for Epoettin alfa
      and darbepoetin alfa administered to patients on dialysis takes effect on April
      1, 2006. The new policy provides several significant improvements that should
      enhance clinicians' ability to manage anemia rationally. However, several aspects
      of the new policy are ambiguous and will require further clarification and
      ongoing evaluation to determine the effect on practice patterns and clinical
      outcomes.

PMID- 16613416
TI  - Determining maturity of new arteriovenous fistulae.

PMID- 16613417
TI  - Peritoneal dialysis as the treatment of choice for pediatric patients. CAPD is
      the best modality for children.
AB  - In our center, we believe that a PD modality should not be arbitrarily assigned
      by the dialysis facility. Rather, the choice of PD modality should be made based
      on the individual child's treatment requirements and PET results as well as the
      family's strengths, challenges, and desires (Harmon et al., 2000). The family has
      the choice whether to use CCPD or CAPD. Families and children who are able to
      switch back and forth between the two modalities as needed are the most flexible
      and most successful because they can build their therapy around their lifestyle
      and not the other way around (Hislop & Lansing, 1983).

PMID- 16613418
TI  - Peritoneal dialysis as the treatment of choice for pediatric patients. CCPD is
      the therapy of choice for pediatric patients with ESRD.

PMID- 16613419
TI  - Non-dietary causes of hyperkalemia.
AB  - This discussion is not all inclusive of nondietary causes of hyperkalemia, but is
      meant to alert healthcare providers to possible factors other than excessive
      dietary potassium intake.

PMID- 16613420
TI  - "Fistula Force"--a team approach to Fistula First.

PMID- 16613421
TI  - The legislative process and the Kidney Care Quality and Improvement Act of 2005.

PMID- 16613422
TI  - Encroachment into practice.

PMID- 16613423
TI  - Toward a developmental psychopathology approach to borderline personality
      disorder.

PMID- 16613424
TI  - Emotion dysregulation and the development of borderline personality disorder.
AB  - We review the role of emotion regulation in borderline personality disorder
      (BPD). We briefly discuss the historical development of BPD as a disorder where
      emotional regulation plays a key role. We review the concept of emotion
      regulation in general and explore both one-factor and two-factor models of
      emotion regulation. We discuss cognitive and attentional aspects of emotion
      regulation, and explore these regulatory controls as operating as both voluntary
      as well as automatic processes. We then turn to other neurophysiological models
      of emotion regulation in general and examine how those models, both
      neurophysiologically and neuroanatomically, are expressed in individuals with
      BPD. We examine how neuroimaging, both anatomical and functional, reveals the
      roles that various neuroanatomical structures play in the regulation of emotion
      in BPD. We conclude by creating a neurodevelopmental model that describes how a
      complex matrix involving the interplay of constitutional/biological
      predispositions with environmental stressors as well as with parental
      effectiveness in response to the child's emotion expression can impact key
      aspects of adult cognitive, affective, interpersonal, and behavioral functioning
      that culminate in a diagnosis of BPD.

PMID- 16613425
TI  - The psychodynamics of borderline personality disorder: a view from developmental
      psychopathology.
AB  - This article provides a contemporary view of the psychodynamics of borderline
      personality disorder (BPD) from a developmental psychopathology perspective. We
      first briefly describe the evolution of the borderline construct in
      psychoanalysis and psychiatry. Then we provide clinically and empirically
      informed model of domains of personality function and dysfunction that provides a
      roadmap for thinking about personality pathology from a developmental
      psychopathology standpoint and examine the nature and phenomenology of BPD in
      terms of these domains of functioning. Next, we describe prominent dynamic
      theories of etiology of BPD and examine these in relation to the available
      research. Finally, we describe psychodynamic conceptions of treatment and the way
      BPD phenomena manifest in treatment, followed again by consideration of relevant
      research, particularly on transference-countertransference constellations
      empirically identified in the treatment of patients with BPD.

PMID- 16613426
TI  - The implications of attachment theory and research for understanding borderline
      personality disorder.
AB  - Borderline personality disorder (BPD) is a highly prevalent, chronic, and
      debilitating psychiatric problem characterized by a pattern of chaotic and self
      defeating interpersonal relationships, emotional lability, poor impulse control,
      angry outbursts, frequent suicidality, and self-mutilation. Recently,
      psychopathology researchers and theorists have begun to understand fundamental
      aspects of BPD such as unstable, intense interpersonal relationships, feelings of
      emptiness, bursts of rage, chronic fears of abandonment and intolerance for
      aloneness, and lack of a stable sense of self as stemming from impairments in the
      underlying attachment organization. These investigators have noted that the
      impulsivity, affective lability, and self-damaging actions that are the hallmark
      of borderline personality occur in an interpersonal context and are often
      precipitated by real or imagined events in relationships. This article reviews
      attachment theory and research as a means of providing a developmental
      psychopathology perspective on BPD. Following a brief review of Bowlby's theory
      of attachment, and an overview of the evidence with respect to the major claims
      of attachment theory, I discuss individual differences, the evidence that these
      differences are rooted in patterns of interaction with caregivers, and how these
      patterns have important implications for evolving adaptations and development.
      Following this discussion, I present recent work linking attachment theory and
      BPD, focusing on the implications for understanding the etiology and treatment of
      BPD. In conclusion, I address some of the salient issues that point to the
      direction for future research efforts.

PMID- 16613427
TI  - The developmental line of autonomy in the etiology, dynamics, and treatment of
      borderline personality disorders.
AB  - Borderline personality disorder (BPD) is considered as a disorder of autonomy,
      and is related to both predisposing vulnerabilities and social relationships that
      fail to support basic psychological needs. Autonomy, which is defined within the
      self-determination theory as the capacity for self-endorsed action based on
      integrative, reflective awareness, is discussed as a developmental line that is
      dependent on specific supports from caregivers. Unresponsiveness, invalidation,
      or abuse by caregivers is argued to impair the capacity for autonomy and to
      catalyze an array of processes, both biological and psychological, which impact
      subsequent development and, in vulnerable individuals, can lead to BPD. Aspects
      of treatment, including the emphases on validation and acceptance of the
      patient's experience, and the cultivation of more reflective or mindful
      regulation of behavior, can be deduced, from this analysis of autonomy
      disturbance, and these in turn have appeared as the cornerstones of effective
      treatments for BPD.

PMID- 16613428
TI  - Family interaction and the development of borderline personality disorder: a
      transactional model.
AB  - Although no prospective epidemiological studies have evaluated the relationship
      between family interactions and the development of borderline personality
      disorder (BPD), there is considerable evidence for the central role of family
      interactions in the development of BPD. This paper describes the role of family
      interactions or processes, especially those that might be regarded as
      invalidating or conflictual, negative or critical, and the absence of more
      validating, positive, supportive, empathic interactions, in the development of
      BPD. Perhaps more importantly, the proposed model considers how these parental
      and family behaviors transact with the child's own behaviors and emotional
      vulnerabilities, resulting in a developmental model of BPD that is neither
      blaming of the family member with BPD nor of her or his parents and caregivers,
      and has important and specific implications for both prevention and intervention.

PMID- 16613429
TI  - Developmental precipitants of borderline personality disorder.
AB  - Traditional theories regarding the etiology of borderline personality disorder
      have focused on poor attachment figures and/or traumatic experience. The present
      review posits an additional pathogenic course for this disorder. Specifically,
      the proposed mechanism involves a basic disruption of the neural hardware that
      supports the formation and maintenance of unconscious emotional memory, hardware
      essential for the formation of early attachments. It is further theorized that
      this early disruption has ongoing effects on both behavioral and concomitant
      neural development. Within this model, adolescence is described as a period of
      intense change that serves as the tipping point for the onset of borderline
      personality disorder.

PMID- 16613430
TI  - Borderline personality features in childhood: a short-term longitudinal study.
AB  - Borderline personality disorder is a particularly devastating, yet understudied
      form of psychopathology. One of the most significant gaps in existing knowledge
      is the lack of systematic, prospective empirical attention to the developmental
      precursors of borderline personality. The present investigation was an
      exploratory attempt to address this limitation through (a) development of a
      psychometrically sound self-report instrument that assesses borderline
      personality features in childhood, the Borderline Personality Features Scale for
      Children (BPFS-C); (b) examination of the stability of BPF in childhood; (c)
      evaluation of gender differences in BPF in childhood; and (d) evaluation of the
      specificity of the BPFS-C for assessing borderline personality features. These
      goals were achieved through the prospective study of a normative sample of 400
      (54% female) fourth though sixth graders who were assessed during the Fall of
      Year 1, Spring of Year 1, and Fall of Year 2. The use of linear mixed modeling
      techniques provided evidence for the construct validity of the BPFS-C. Further,
      borderline personality features as assessed with the BPFS-C were found to be
      moderately stable over the course of the study, with girls reporting higher
      levels of BPF than boys. Results also demonstrated that children's scores on the
      BPFS-C were uniquely related to indicators of borderline personality pathology
      above and beyond their scores on the Children's Depression Inventory. The
      implications of these results for the study of the development and etiology of
      borderline pathology are discussed.

PMID- 16613432
TI  - The development of impulsivity and suicidality in borderline personality
      disorder.
AB  - Borderline personality disorder (BPD) is characterized by a broad pattern of
      impulsivity and suicidality. BPD usually begins in adolescence; the full clinical
      picture of the disorder is associated with developmental increases in
      impulsivity. However, BPD also has childhood precursors. The developmental
      pathways are similar to those found in other impulsive spectrum disorders, but
      children who later develop BPD probably have both externalizing and internalizing
      symptoms. Research in this area has made use of retrospective data from adults,
      prospective data from community studies, follow-up studies from children at risk,
      as well as research on "borderline pathology of childhood" (a condition with
      symptoms similar to adult BPD). Existing evidence suggests that both
      temperamental and environmental risk factors play a role in the development of
      the behavioral patterns associated with the disorder. These pathways also help
      account for the life course and outcome of BPD in adulthood.

PMID- 16613431
TI  - Child maltreatment, attention networks, and potential precursors to borderline
      personality disorder.
AB  - Potential precursors to borderline personality disorder (BPD) were investigated
      in a sample of 185 maltreated and 175 nonmaltreated school-aged children
      attending a summer camp research program. Self-report, peer-report, and counselor
      report measures were utilized to assess developmental constructs conceptualized
      to constitute vulnerability for later emerging BPD. These areas, including
      personality features, representational models of self, parent, and peers,
      interpersonal relationship difficulties with peers and adults, and suicidal/self
      harm behavior, were used to develop a BPD precursors composite. Additionally, the
      efficiency of three attention networks was assessed with a computerized task.
      Maltreated children had higher mean scores on the BPD precursors composite, and
      children classified as having high levels of these precursors were more prevalent
      in the maltreatment group. No maltreatment group differences were found for the
      efficiency of the three attention networks; however, children with high levels of
      BPD precursors evinced less efficient processing of the conflict attention
      network, comparable to findings observed among adult patients with BPD. Child
      maltreatment and efficiency of the conflict attention network independently
      predicted scores on the BPD precursors composite. Experiential and biological
      contributions to risk for BPD and recommendations for prevention and intervention
      are discussed.

PMID- 16613433
TI  - Psychological, autonomic, and serotonergic correlates of parasuicide among
      adolescent girls.
AB  - Although parasuicidal behavior in adolescence is poorly understood, evidence
      suggests that it may be a developmental precursor of borderline personality
      disorder (BPD). Current theories of both parasuicide and BPD suggest that emotion
      dysregulation is the primary precipitant of self-injury, which serves to dampen
      overwhelmingly negative affect. To date, however, no studies have assessed
      endophenotypic markers of emotional responding among parasuicidal adolescents. In
      the present study, we compare parasuicidal adolescent girls (n=23) with age
      matched controls (n=23) on both psychological and physiological measures of
      emotion regulation and psychopathology. Adolescents, parents, and teachers
      completed questionnaires assessing internalizing and externalizing
      psychopathology, substance use, trait affectivity, and histories of parasuicide.
      Psychophysiological measures including electrodermal responding (EDR),
      respiratory sinus arrhythmia, and cardiac pre-ejection period (PEP) were
      collected at baseline, during negative mood induction, and during recovery.
      Compared with controls, parasuicidal adolescents exhibited reduced respiratory
      sinus arrhythmia (RSA) at baseline, greater RSA reactivity during negative mood
      induction, and attenuated peripheral serotonin levels. No between-group
      differences on measures of PEP or EDR were found. These results lend further
      support to theories of emotion dysregulation and impulsivity in parasuicidal
      teenage girls.

PMID- 16613434
TI  - Disinhibition and borderline personality disorder.
AB  - We review different conceptions of inhibitory control that may be relevant to the
      regulatory problems featured in borderline personality disorder (BPD). These
      conceptions have often been framed with regard to personality traits of
      inhibitory control, but can also be related to cognitive measures of response
      suppression as well as affect regulation. Reactive behavioral inhibition is
      relatively unstudied in relation to BPD. A substantial amount of literature links
      executive function problems with BPD, but that literature has not isolated
      executive response inhibition nor been controlled for other personality disorder
      symptoms of antisociality, attention-deficit/hyperactivity disorder (ADHD), or
      depression, anxiety, or posttraumatic symptoms. We therefore conducted a study of
      this question looking at BPD symptoms in an adult sample with a small number of
      BPD subjects and other disorders. Results indicated that symptoms of BPD were
      correlated with response inhibition (measured by stop signal reaction time) even
      after controlling for the overlap of stop inhibition with ADHD, antisociality,
      and other Axis II disorder symptoms. We conclude by hypothesizing discrete
      developmental routes to BPD, based on different mechanism breakdowns, which would
      be amenable to empirical investigation at the cognitive or trait level of
      analysis.

PMID- 16613435
TI  - Developmental psychopathology and neurobiology of aggression.
AB  - The aim of this paper is to clarify how neural mechanisms at the molecular level,
      specifically the serotonergic (5-HT) system and the hypothalamic-pituitary
      adrenal axis system (HPA) in conjunction with early life stress may contribute to
      the emergence of aggression, self-directed and otherwise, in borderline
      personality disorder (BPD). Chronic dysregulation of these biological systems,
      which function to regulate stress and emotion, may potentiate the development of
      impulsive aggression in borderline personality conditions. Our central premise in
      this paper is that brain development, stress regulation, and early pathonomic
      experience are interactive and cumulative in their mutual influence on the
      development of impulsive aggression in BPD. We review the parameters of impulsive
      aggression in BPD, followed by a discussion of the neurobiological and
      neuroendocrine correlates of impulsive aggression with and without BPD. We then
      focus on the developmental continuities in BPD with attention to brain maturation
      of 5-HT and HPA axis function during the life span and the influence of early
      adverse experiences on these systems. Finally, we comment on the data of the
      relative stability of aggression in BPD, adolescence as a developmental stage of
      potential vulnerability, and the course of aggressive behavior during the life
      span.

PMID- 16613436
TI  - Neurocognitive impairment as a moderator in the development of borderline
      personality disorder.
AB  - Borderline personality disorder (BPD) is characterized by a pervasive instability
      of interpersonal relationships, affects, self-image, marked impulsivity,
      dissociation, and paranoia. The cognitive dimension of the disorder has received
      relatively little attention and is poorly understood. This paper proposes that
      neurocognitive impairment is a key moderator in the development of BPD and
      elaborates a possible pathway for the expression of the cognitive domain.
      Neurocognitive impairment is hypothesized to moderate the relationship between
      caretaking and insecure disorganized attachment and pathological dissociation in
      the formation of the disorder contributing to impaired metacognition and a range
      of cognitive difficulties. The empirical evidence from studies of cognitive
      processes, brain function, attachment, and dissociation that support this theory
      are reviewed and discussed. Areas for future research that might verify or refute
      this theory are suggested.

PMID- 16613437
TI  - Defining the neurocircuitry of borderline personality disorder: functional
      neuroimaging approaches.
AB  - Functional neuroimaging recently has been used to localize brain dysfunction in
      borderline personality disorder (BPD). Initial studies have examined baseline
      activity or emotional reactivity, and our group has investigated what we consider
      to be a crucial interaction between negative emotion and behavioral (dys)control.
      This research is beginning to identify abnormal frontolimbic circuitry likely
      underlying core clinical features of this condition. We review the evidence for
      dysfunction in specific frontolimbic regions, leading to a mechanistic model of
      symptom formation in BPD. In addition, we offer an integration of these
      neuroimaging findings with developmental perspectives on the emergence of
      borderline psychopathology, focusing on the ways in which early psychosocial
      experience may interact with developing brain systems. We also consider possible
      mechanisms of psychotherapeutic change at the neural systems level in BPD.
      Finally, we propose that future neuroimaging studies of BPD should integrate
      multiple levels of observation (structural, functional, neurochemical, genetic,
      and clinical) in a model-driven fashion to further understand the dynamic
      relationship between biological and psychological factors in the development and
      treatment of this difficult condition.

PMID- 16613439
TI  - Atomic scale control of single molecule charging.
AB  - A scanning tunneling microscope was used to study charging of single copper
      phthalocyanine molecules adsorbed on an ultrathin Al(2)O(3) film grown on a
      NiAl(110) surface. A double-barrier tunnel junction is formed by a vacuum barrier
      between the tip and the molecule and an oxide barrier between the molecule and
      the NiAl. In this geometry the molecule can be charged by the tunneling
      electrons. This charging was found to be strongly dependent on the position of
      the tip above the molecule and the applied bias voltage.

PMID- 16613438
TI  - Predicting change in borderline personality: Using neurobehavioral systems
      indicators within an individual growth curve framework.
AB  - The natural history and course of borderline personality disorder (BPD) has long
      been the focus of speculation, typically guided by impressions from clinical work
      with BPD-affected individuals. Not unlike the other personality disorders (PDs),
      it has long been assumed that BPD is relatively stable, traitlike, and enduring
      in nature. The extent to which BPD is or is not a plastic construct has
      implications not only for understanding its longitudinal course, but also for
      understanding its development and, ultimately, its treatment and/or prevention.
      This paper consists of two parts. The first part reviews the longitudinal
      research corpus that bears directly upon the issue of stability of BPD in both
      adolescents and adults. The consistent trend in very nearly all studies, whether
      using a categorical or dimensional approach to assessment, is one of considerable
      change over time. This literature presents complexities, however, because most of
      the extant studies examine BPD-affected individuals who have been exposed to
      treatment. However, at least two large-scale longitudinal studies, which include
      both treated and untreated persons, also provide support for viewing BPD as a
      malleable disorder that declines in severity over time. The second part presents
      original data from the Longitudinal Study of Personality Disorders that
      specifically examine the predictors of change in BPD using a neurobehavioral
      model of personality within an individual growth curve (IGC) analytical
      framework. This IGC analysis revealed important predictors of both overall level
      of BPD features as well as rate of change in BPD features, with particularly
      important roles played by the agentic positive emotion (i.e., incentive
      motivation) and anxiety (negative emotion) systems. The benefits of the IGC
      approach for understanding the developmental psychopathology of BPD is also
      stressed.

PMID- 16613440
TI  - The calculated infrared spectrum of Cl- H2O using a full dimensional ab initio
      potential surface and dipole moment surface.
AB  - We report a full dimensional ab initio-based global potential energy surface
      (PES) and dipole moment surface (DMS) for Cl(-)H(2)O. Both surfaces are symmetric
      with respect to interchange of the H atoms. The PES is a fit to thousands of
      electronic energies calculated using the coupled-cluster method (CCSD(T)) with a
      moderately large basis (aug-cc-pVTZ). The infrared spectrum and vibrational
      dynamics are reported and compared to experiment. These results are analyzed by
      examination of wave function and the dipole surface.

PMID- 16613441
TI  - Close-packed structures and phase diagram of soft spheres in cylindrical pores.
AB  - It is shown for a model system consisting of spherical particles confined in
      cylindrical pores that the first ten close-packed phases are in one-to-one
      correspondence with the first ten ways of folding a triangular lattice, each
      being characterized by a roll-up vector like the single-walled carbon nanotube.
      Phase diagrams in pressure-diameter and temperature-diameter planes are obtained
      by inherent-structure calculation and molecular dynamics simulation. The phase
      boundaries dividing two adjacent phases are infinitely sharp in the low
      temperature limit but are blurred as temperature is increased. Existence of such
      phase boundaries explains rich, diameter-sensitive phase behavior unique for
      cylindrically confined systems.

PMID- 16613442
TI  - Bilayer vesicles as precursors for spherical fractal aggregates from the self
      assembly of a C60-fullerene-dyad in polar solvent.
AB  - Spherical fractal aggregates of approximately 10 microm were formed from a pi
      electronic amphiphile, C(60)-didodecyloxybenzene dyad when extracted from THF
      into water, necessitating a critical dielectric constant epsilon > or =30 in
      binary THF-water mixtures. Molecular dynamics simulations revealed the unit
      cluster to such a form involves an aggregation number approximately 90 with
      predominant soft associative molecular interactions which corroborated the
      octadecahedral model proposed for the cluster growth.

PMID- 16613443
TI  - Mutual information and electron correlation in momentum space.
AB  - Mutual information and information entropies in momentum space are proposed as
      measures of the nonlocal aspects of information. Singlet and triplet state
      members of the helium isoelectronic series are employed to examine Coulomb and
      Fermi correlations, and their manifestations, in both the position and momentum
      space mutual information measures. The triplet state measures exemplify that the
      magnitude of the spatial correlations relative to the momentum correlations
      depends on and may be controlled by the strength of the electronic correlation.
      The examination of one- and two-electron Shannon entropies in the triplet state
      series yields a crossover point, which is characterized by a localized momentum
      density. The mutual information density in momentum space illustrates that this
      localization is accompanied by strong correlation at small values of p.

PMID- 16613444
TI  - Order-parameter-based Monte Carlo simulation of crystallization.
AB  - A Monte Carlo simulation method is presented for simulation of phase transitions,
      with emphasis on the study of crystallization. The method relies on a random walk
      in order parameter Phi(q(N)) space to calculate a free energy profile between the
      two coexisting phases. The energy and volume data generated over the course of
      the simulation are subsequently reweighed to identify the precise conditions for
      phase coexistence. The usefulness of the method is demonstrated in the context of
      crystallization of a purely repulsive Lennard-Jones system. A systematic analysis
      of precritical and critical nuclei as a function of supercooling reveals a
      gradual change from a bcc to a fcc structure inside the crystalline nucleus as it
      grows at large degrees of supercooling. The method is generally applicable and is
      expected to find applications in systems for which two or more coexisting phases
      can be distinguished through one or more order parameters.

PMID- 16613445
TI  - Computing the density of paths in complex systems.
AB  - Trajectories of duration tau joining two points q(0) and q(1) in the
      configuration space of a classical system satisfy Hamilton's principle: they are
      stationary points of the classical action. The second variation (fluctuations) of
      the action around the stationary point signals whether the latter is or not a
      minimum and delivers the density in trajectory space around the points q(0) and
      q(1). This concept of density of paths is of great importance in semiclassical
      quantum theory, where it weights the contribution to the propagator from the
      single classical trajectories. In this paper, two algorithms based on the
      concepts of molecular dynamics simulation are introduced for computing the
      density of paths, also called van Vleck [Proc. Natl. Acad. Sci. U.S.A. 14, 178
      (1928)] determinant. Examples for realistic systems are presented, together with
      a suggestion about possible applications in the field of rare events in physics
      and chemistry.

PMID- 16613446
TI  - A coherent state approach to semiclassical nonadiabatic dynamics.
AB  - A semiclassical (SC) approximation to the quantum mechanical propagator for
      nonadiabatic systems is derived. Our derivation starts with an exact path
      integral expression that uses canonical coherent states for the nuclear degrees
      of freedom and spin coherent states for the electronic degrees of freedom. A
      stationary path approximation (SPA) is then applied to the path integral to
      obtain the SC approximation. The SPA results in complex classical trajectories of
      both nuclear and electronic degrees of freedom and a double ended boundary
      condition. The root search problem is solved using the previously proposed "real
      trajectory local search" algorithm. The SC approximation is tested on three
      simple one dimensional two-state systems proposed by Tully [J. Chem. Phys. 93,
      1061 (1990)], and the SC results are compared to Ehrenfest and surface hopping
      predictions. Excellent agreement with quantum results is reached when the SC
      trajectory is far away from caustics. We discuss the origin of caustics in this
      SC formalism and the strengths and weaknesses of this approach.

PMID- 16613447
TI  - Multimode wavelet basis calculations via the molecular self-consistent-field plus
      configuration-interaction method.
AB  - Wavelets provide potentially useful quantum bases for coupled anharmonic
      vibrational modes in polyatomic molecules as well as many other problems. A
      single compact support wavelet family provides a flexible basis with properties
      of orthogonality, localization, customizable resolution, and systematic
      improvability for general types of one-dimensional and separable systems. While
      direct product wavelet bases can be used in coupled multidimensional problems,
      exponential scaling of basis size with dimensionality ultimately provides limits
      on the number of coupled modes that can be treated simultaneously in exact
      quantum calculations. The molecular self-consistent-field plus configuration
      interaction method is used here in multimode wavelet calculations to reduce the
      basis size without sacrificing flexibility or the ability to systematically
      control errors. Both two-dimensional Cartesian coordinate and three-dimensional
      curvilinear coordinate systems are examined with wavelets serving as universal
      bases in each case. The first example uses standard Daubechies [Ten Lectures on
      Wavelets (SIAM, Philadelphia (1992)] wavelets for each mode and the second adapts
      symmlet wavelets to intervals for each of the curvilinear coordinates.

PMID- 16613448
TI  - Numerical solution of Dalgarno-Lewis equations by a mapped Fourier grid method.
AB  - Inhomogeneous radial differential equations emerging in applications of standard
      perturbation theory are numerically solved by a novel approach making use of
      Fourier grid methods in conjunction with a simple mapping scheme. The proposed
      algorithm is applied along the lines of the Dalgarno-Lewis method [Proc. R. Soc.
      London, Ser. A 223, 70 (1955)] to the calculation of the static dipole
      polarizabilities and hyperpolarizabilities of 1s, 2s, and 2p states of hydrogen
      atom and their frequency dependent dynamic dipole polarizabilities. The high
      efficiency and accuracy of the algorithm are demonstrated for the above test
      cases, where exact values are available. Then, the frequency dependent dipole
      polarizability of the ground state of lithium atom is computed by a variationally
      stable method combining an effective local potential approach with a second-order
      energy correction. The obtained results are in perfect agreement with other
      elaborate theoretical approaches.

PMID- 16613449
TI  - Nonadiabatic reactant-product decoupling calculation for the F(2P(1/2)) + H2
      reaction.
AB  - In this paper we present a theoretical study using time-dependent nonadiabatic
      reactant-product decoupling method for the state-to-state reactive scattering
      calculation of F((2)P(1/2))+H(2) (nu=j=0) reaction on the Alexander-Stark-Werner
      potential energy surface. In this nonadiabatic state-to-state calculation, the
      full wave function is partitioned into reactant component and a sum of all
      product components. The reactant and product components of the wave function are
      solved independently. For the excited state reaction, the state-to-state reaction
      probabilities for J=0.5 are calculated. Comparing the state-to-state reaction
      probabilities, it is found that the vibrational population of the HF product is
      dominated by vibrational levels nu=2 and 3. The rotation specific reaction
      probabilities of HF product in j=1 and 2 are larger than those in other
      rotational levels. As the rotation quantum number j increases, the positions of
      the peak in the rotational reaction probability of HF product in nu=3 shift to
      higher collision energy.

PMID- 16613450
TI  - Fluorescence excitation and emission spectroscopy of the A1A"<--X1A' system of
      CHBr.
AB  - We report fluorescence excitation and emission spectra of CHBr in the 450-750 nm
      region. A total of 30 cold bands involving the pure bending levels 2(0)(n) with
      n=2-8 and combination bands 2(0)(n)3(0)(1)(n=1-8), 2(0) (n)3(0)(2)(n=1-6),
      2(0)(n)3(0)(3)(n=1-2), 1(0)(1)2(0)(n)(n=5-7), 1(0)(1)2(0)(n)3(0)(1)(n=4-6), and
      1(0)(1)2(0)(n)3(0)(2)(n=5) in the A (1)A(")<--X (1)A(') system were observed, in
      addition to a number of hot bands. The majority of these are reported and/or
      rotationally analyzed here for the first time. Spectra were measured under jet
      cooled conditions using a pulsed discharge source, and rotational analysis
      yielded band origins and rotational constants for both bromine isotopomers (CH
      (79)Br,CH (81)Br). The derived A (1)A(") vibrational intervals are combined with
      results of [Yu et al. J. Chem. Phys. 115, 5433 (2001)] to derive barriers to
      linearity for the 2(n), 2(n)3(1), and 2(n)3(2) progressions. The A (1)A(") state
      C-H stretching frequency is determined here for the first time, and the observed
      nu(3) dependence of the (79)Br-(81)Br isotope splitting in the A(1)A(") state is
      in good agreement with theoretical expectations. Our dispersed fluorescence
      spectra probe the vibrational structure of the X(1)A(') state up to approximately
      9000 cm(-1) above the vibrationless level; the total number of levels observed is
      more than twice that previously reported. As first reported by [Chen et al. J.
      Mol. Spectrosc. 209, 254 (2001)], these spectra reveal numerous perturbations due
      to spin-orbit interaction with the low-lying a(3)A(") state. The results of a
      Dunham expansion fit of the ground state vibrational term energies, and
      comparisons with previous experimental and theoretical studies, are reported. Our
      results lead to several revised assignments, including the X (1)A(') C-H
      stretching fundamental. Globally, the vibrational frequencies of X(1)A('),
      a(3)A("), and A(1)A(") are in excellent agreement with theoretical predictions.

PMID- 16613451
TI  - Energy transfer of highly vibrationally excited azulene. II. Photodissociation of
      azulene-Kr van der Waals clusters at 248 and 266 nm.
AB  - Photodissociation of azulene-Kr van der Waals clusters at 266 and 248 nm was
      studied using velocity map ion imaging techniques with the time-sliced
      modification. Scattered azulene molecules produced from the dissociation of
      clusters were detected by one-photon vacuum ultraviolet ionization. Energy
      transfer distribution functions were obtained from the measurement of recoil
      energy distributions. The distribution functions can be described approximately
      by multiexponential functions. Fragment angular distributions were found to be
      isotropic. The energy transfer properties show significantly different behavior
      from those of bimolecular collisions. No supercollisions were observed under the
      signal-to-noise ratios S/N=400 and 100 at 266 and 248 nm, respectively.
      Comparisons with the energy transfer of bimolecular collisions in thermal systems
      and the crossed-beam experiment within detection limit are made.

PMID- 16613452
TI  - Photodissociation of the BrO radical using velocity map ion imaging: excited
      state dynamics and accurate D0(0)(BrO) evaluation.
AB  - We have studied the photodissociation dynamics of expansion-cooled BrO radical
      both above (278-281.5 nm) and below (355 nm) the A (2)Pi(3/2) state threshold
      using velocity map ion imaging. A recently developed late-mixing flash pyrolytic
      reactor source was utilized to generate an intense BrO radical molecular beam.
      The relative electronic product branching ratios at 355 nm and from 278 to 281.5
      nm were determined. We have investigated the excited state dynamics based on both
      the product branching and the photofragment angular distributions. We find that
      above the O((1)D(2)) threshold the contribution of the direct excitation to
      states other than the A (2)Pi(3/2) state and the role of curve crossing is
      considerably larger in BrO compared to that observed for ClO, in agreement with
      recent theoretical studies. The measurement of low velocity photofragments
      resulting from photodissociation just above the O((1)D(2)) threshold provides an
      accurate and direct determination of the A (2)Pi(3/2) state dissociation
      threshold of 35418+/-35 cm(-1), leading to a ground state bond energy of
      D(0)(0)(BrO)=55.9+/-0.1 kcal/mol.

PMID- 16613453
TI  - Pulsed-field ionization electron spectroscopy of group 6 metal (Cr, Mo, and W)
      bis(benzene) sandwich complexes.
AB  - Group 6 metal bis(benzene) sandwich complexes (M-bz(2): M=Cr, Mo, and W and
      bz=C(6)H(6)) were produced with laser vaporization molecular beam techniques and
      studied by pulsed-field ionization zero electron kinetic energy spectroscopy and
      density functional theory calculations. Each sandwich complex is in a D(6h)
      eclipsed configuration with (1)A(1g) and (2)A(1g) as the neutral and cationic
      ground electronic states, respectively. The adiabatic ionization energies for Cr
      , Mo-, and W-bz(2) are measured to be 44,081(7), 44,581(10), and 43,634(7) cm(
      1), respectively. The metal-benzene stretch and benzene torsion frequencies of
      the ion are measured to be 264, 277, and 370 cm(-1) and 11, 21, and 45 cm(-1) for
      Cr-, Mo-, and W-bz(2), respectively. In addition, a C-H out-of-plane bending mode
      is measured to be 787 cm(-1) for the Cr(+)-bz(2) complex, while a C-C in-plane
      bending mode is measured to be 614 cm(-1) for the W(+)-bz(2) complex. The unusual
      trend in the ionization energy and metal-benzene stretch frequency indicates
      strong relativistic effects on tungsten binding.

PMID- 16613454
TI  - Molecular dynamics investigations of the dissociation of SiO2 on an ab initio
      potential energy surface obtained using neural network methods.
AB  - The neural network (NN) procedure to interpolate ab initio data for the purpose
      of molecular dynamics (MD) simulations has been tested on the SiO(2) system.
      Unlike other similar NN studies, here, we studied the dissociation of SiO(2)
      without the initial use of any empirical potential. During the dissociation of
      SiO(2) into Si+O or Si+O(2), the spin multiplicity of the system changes from
      singlet to triplet in the first reaction and from singlet to pentet in the
      second. This paper employs four potential surfaces. The first is a NN fit
      [NN(STP)] to a database comprising the lowest of the singlet, triplet, and pentet
      energies obtained from density functional calculations in 6673 nuclear
      configurations. The other three potential surfaces are obtained from NN fits to
      the singlet, triplet, and pentet-state energies. The dissociation dynamics on the
      singlet-state and NN(STP) surfaces are reported. The results obtained using the
      singlet surface correspond to those expected if the reaction were to occur
      adiabatically. The dynamics on the NN(STP) surface represent those expected if
      the reaction follows a minimum-energy pathway. This study on a small system
      demonstrates the application of NNs for MD studies using ab initio data when the
      spin multiplicity of the system changes during the dissociation process.

PMID- 16613455
TI  - Equation of state of nitrogen (N2) at high pressures and high temperatures:
      molecular dynamics simulation.
AB  - Nitrogen equation of state at pressures up to 30 GPa (300 kbars) and temperatures
      above 800 K was studied by molecular dynamics (MD) simulations. The dynamics of
      the N(2) molecules is treated in hard rotor approximation, i.e., it accounts both
      translational and rotational degrees of freedom. The rotational motion of the
      N(2) molecule is treated assuming constant moment of inertia of the nitrogen
      molecule. The new MD program fully accounts anisotropic molecular nitrogen
      interaction. The N(2)-N(2) interaction potential has been derived by van der
      Avoird et al. [J. Chem. Phys. 84, 1629 (1986)] using the results of high
      precision Hartree-Fock ab initio quantum mechanical calculations. The potential,
      fully accounts rotational symmetry of the N(2)-N(2) system, by employing 6-j
      Wigner symbols, i.e., preserving full rotational symmetry of the system. Various
      numerical algorithms were tested, in order to achieve the energy preservation
      during the simulation. It has been demonstrated that the standard Verlet
      algorithm was not preserving the energy for the standard MD time step, equal to
      5x10(-16) s. Runge-Kutta fourth order method was able to preserve the energy
      within 10(-4) relative error, but it requires calculation of the force four times
      for each time step and therefore it is highly inefficient. A predictor-corrector
      method of the fifth order (PC5) was found to be efficient and precise and was
      therefore adopted for the simulation of the molecular nitrogen properties at high
      pressure. Singer and Fincham algorithms were tested and were found to be as
      precise as PC5 algorithm and they were also used in the simulation of the
      equation of state. Results of MD simulations are in very good agreement with the
      experimental data on nitrogen equation of state at pressures below 1 GPa (10
      kbars). For higher pressures, up to 30 GPa (300 kbars), i.e., close to molecular
      nitrogen stability limit, determined by Nellis et al. [Phys. Rev. Lett. 85, 1262
      (1984)], the obtained numerical results provide new data of the experimentally
      unexplored region. These data were formulated in the analytical form of pressure
      density-temperature equation of state.

PMID- 16613456
TI  - Thermodynamics of symmetric dimers: lattice density functional theory predictions
      and simulations.
AB  - A new lattice density functional theory (DFT) approach is proposed for symmetric
      dimers taking into account all possible configurations for molecules adjacent to
      a central dimer. Comparison with Monte Carlo simulations shows significant
      improvement of the proposed model compared to previously developed version of
      lattice DFT for dimers. It is shown that the new model gives accurate analytical
      solutions over a wide range of densities and temperatures. Phase transitions in
      dimers are analyzed and fundamental differences between dimers and monomers are
      discussed.

PMID- 16613457
TI  - The dynamic susceptibility in glass forming molecular liquids: the search for
      universal relaxation patterns II.
AB  - The susceptibility spectra of ten molecular glass formers are completely
      interpolated by an extension of the generalized gamma distribution of correlation
      times. The data cover at least 15 decades in frequency and the interpolation
      includes both alpha peak and excess wing. It is shown that the line shape
      parameters and the time constant of the alpha relaxation are related to each
      other. Master curves are identified by a scaling procedure that involves only
      three parameters, namely, the glass transition temperature T(g), the fragility m,
      and the excess wing exponent at T(g). This holds independent of whether a further
      secondary relaxation peak is present or not. Above a crossover temperature T(x)
      this unique evolution of the line shape parameters breaks down, and a crossover
      to a simple peak susceptibility without excess wing is observed. Here, the
      frequency-temperature superposition principle holds in good approximation up to
      temperatures well above the melting point. It turns out that the crossover
      coincides with the temperature at which the low-temperature Vogel-Fulcher law
      starts to fail upon heating. Thus, the so-called Stickel temperature gets a more
      physical meaning as it marks a qualitative change in the evolution of the
      susceptibility spectra of glass formers. Moreover, the interrelation of the line
      shape parameters can explain why the "Nagel scaling" works in some approximation.
      Our study demonstrates that the excess wing in molecular glass formers is a
      secondary relaxation, which is linked to the alpha process in a unique way.

PMID- 16613458
TI  - Soft sticky dipole-quadrupole-octupole potential energy function for liquid
      water: an approximate moment expansion.
AB  - A new, efficient potential energy function for liquid water is presented here.
      The new model, which is referred here as the soft sticky dipole-quadrupole
      octupole (SSDQO) model, describes a water molecule as a Lennard-Jones sphere with
      point dipole, quadrupole, and octupole moments. It is a single-point model and
      resembles the hard-sphere sticky dipole potential model for water by Bratko et
      al. [J. Chem. Phys. 83, 6367 (1985)] and the soft sticky dipole model by Ichiye
      and Liu [J. Phys. Chem. 100, 2723 (1996)] except now the sticky potential
      consists of an approximate moment expansion for the dimer interaction potential,
      which is much faster than the true moment expansion. The object here is to
      demonstrate that the SSDQO potential energy function can accurately mimic the
      potential energy function of a multipoint model using the moments of that model.
      First, the SSDQO potential energy function using the dipole, quadruple, and
      octupole moments from SPC/E, TIP3P, or TIP5P is shown to reproduce the dimer
      potential energy functions of the respective multipoint model. In addition, in
      Monte Carlo simulations of the pure liquid at room temperature, SSDQO reproduces
      radial distribution functions of the respective model. However, the Monte Carlo
      simulations using the SSDQO model are about three times faster than those using
      the three-point models and the long-range interactions decay faster for SSDQO
      (1/r(3) and faster) than for multipoint models (1/r). Moreover, the contribution
      of each moment to the energetics and other properties can be determined. Overall,
      the simplicity, efficiency, and accuracy of the SSDQO potential energy function
      make it potentially very useful for studies of aqueous solvation by computer
      simulations.

PMID- 16613459
TI  - Isotope quantum effects in water around the freezing point.
AB  - We have measured the difference in electronic structure factors between liquid
      H(2)O and D(2)O at temperatures of 268 and 273 K with high energy x-ray
      diffraction. These are compared to our previously published data measured from
      279 to 318 K. We find that the total structural isotope effect increases by a
      factor of 3.5 over the entire range, as the temperature is decreased. Structural
      isochoric temperature differential and isothermal density differential functions
      have been used to compare these data to a thermodynamic model based upon a simple
      offset in the state function. The model works well in describing the magnitude of
      the structural differences above approximately 310 K, but fails at lower
      temperatures. The experimental results are discussed in light of several quantum
      molecular dynamics simulations and are in good qualitative agreement with recent
      temperature dependent, rotationally quantized rigid molecule simulations.

PMID- 16613460
TI  - Application of Fokker-Planck-Kramers equation treatment for short-time dynamics
      of diffusion-controlled reaction in supercritical Lennard-Jones fluids over a
      wide density range.
AB  - The validity of a Fokker-Planck-Kramers equation (FPKE) treatment of the rate of
      diffusion-controlled reaction at short times [K. Ibuki and M. Ueno, J. Chem.
      Phys. 119, 7054 (2003)] is tested in a supercritical Lennard-Jones fluid over a
      wide density range by comparing it with the Langevin dynamics and molecular
      dynamics simulations and other theories. The density n range studied is
      0.323n(c)< or =n< or =2.58n(c) and the temperature 1.52T(c), where n(c) and T(c)
      are the critical density and temperature, respectively. For the rate of
      bimolecular reactions, the transition between the collision-limited and diffusion
      limited regimes is expected to take place in this density range. The simulations
      show that the rate constant decays with time extensively at high densities, and
      that the magnitude of decay decreases gradually with decreasing density. The
      decay profiles of the rate constants obtained by the simulations are reproduced
      reasonably well by the FPKE treatment in the whole density range studied if a
      continuous velocity distribution is used in solving the FPKE approximately. If a
      discontinuous velocity distribution is used instead of the continuous one, the
      FPKE treatment leads to a rate constant much larger than the simulation results
      at medium and low densities. The rate constants calculated from the Smoluchowski
      Collins-Kimball (SCK) theory based on the diffusion equation are somewhat smaller
      than the simulation results in medium and low densities when the intrinsic rate
      constant is chosen to adjust the steady state rate constant in the low density
      limit to that derived by the kinetic collision theory. The discrepancy is
      relatively small, so that the SCK theory provides a useful guideline for a
      qualitative discussion of the density effect on the rate constant.

PMID- 16613461
TI  - Partial molar volume of n-alcohols at infinite dilution in water calculated by
      means of scaled particle theory.
AB  - The partial molar volume of n-alcohols at infinite dilution in water is smaller
      than the molar volume in the neat liquid phase. It is shown that the formula for
      the partial molar volume at infinite dilution obtained from the scaled particle
      theory equation of state for binary hard sphere mixtures is able to reproduce in
      a satisfactory manner the experimental data over a large temperature range. This
      finding implies that the packing effects play the fundamental role in determining
      the partial molar volume at infinite dilution in water also for solutes, such as
      n-alcohols, forming H bonds with water molecules. Since the packing effects in
      water are largely related to the small size of its molecules, the latter feature
      is the ultimate cause of the decrease in partial molar volume associated with the
      hydrophobic effect.

PMID- 16613462
TI  - Anisotropic dynamics of dipolar liquids in narrow slit pores.
AB  - We report molecular dynamics simulation results for Stockmayer fluids confined to
      narrow slitlike pores with structureless, nonconducting walls. The translational
      and rotational dynamics of the dipolar particles have been investigated by
      calculating autocorrelation functions, diffusion coefficients, and relaxation
      times for various pore widths (five or less particle diameters) and directions
      parallel and perpendicular to the walls. The dynamic properties of the confined
      systems are compared to bulk properties, where corresponding bulk and pore states
      at the same temperature and chemical potential are determined in parallel grand
      canonical Monte Carlo simulations. We find that the dynamic behavior inside the
      pore depends on the distance from the walls and can be strongly anisotropic even
      in globally isotropic systems. This concerns especially the particles in the
      surface layers close to the walls, where the single particle and collective
      dipolar relaxation resemble that of true two-dimensional dipolar fluids with
      different in-plane and out-of-plane relaxations. On the other hand, bulklike
      relaxation is observed in the pore center of sufficiently wide pores.

PMID- 16613463
TI  - Mesoscale simulation of morphology in hydrated perfluorosulfonic acid membranes.
AB  - Current fuel cell proton exchange membranes rely on a random network of
      conducting hydrophilic domains to transport protons across the membrane. Despite
      extensive investigation, details of the structure of the hydrophilic domains in
      these membranes remain unresolved. In this study a dynamic self-consistent mean
      field theory has been applied to obtain the morphologies of hydrated
      perfluorosulfonic acid membranes (equivalent weight of 1100) as a model system
      for Nafion at several water contents. A coarse-grained mesoscale model was
      developed by dividing the system into three components: backbone, side chain, and
      water. The interaction parameters for this model were generated using classical
      molecular dynamics. The simulated morphology shows phase separated micelles
      filled with water, surrounded by side chains containing sulfonic groups, and
      embedded in the fluorocarbon matrix. The size distribution and connectivity of
      the hydrophilic domains were analyzed and the small angle neutron scattering
      (SANS) pattern was calculated. At low water content (lambda<6, where lambda is
      the number of water molecules per sulfonic group) the isolated domains obtained
      from simulation are nearly spherical with a domain size smaller than that fitted
      to experimental SANS data. At higher water content (lambda>8), the domains deform
      into elliptical and barbell shapes as they merge. The simulated morphology,
      hydrophilic domain size and shape are generally consistent with some experimental
      observations.

PMID- 16613464
TI  - Forces between chemically structured substrates mediated by critical fluids.
AB  - We consider binary liquid mixtures close to their critical points confined by two
      parallel, geometrically flat, and chemically structured substrates. Universal
      order parameter profiles are calculated within mean field theory for periodic
      patterns of stripes with alternating preferences for the two species of the
      mixture and with different relative positions of the two substrates. From the
      order parameter profiles the effective forces between the two plates are derived.
      The tuning of Casimir amplitudes is discussed.

PMID- 16613465
TI  - Quantitative determination of the single-molecule detection regime in
      fluorescence fluctuation microscopy by means of photon counting histogram
      analysis.
AB  - Fluorescence fluctuation experiments are performed in single-molecule detection
      regime if the fluorescence of at most one molecule is registered at a time.
      Although the significance of such experiments for investigations of complex
      nonergodic systems like those met in the biosciences has been stressed out by
      many scientists, the quantitative and accurate determination of the single
      molecule detection regime received rather little attention. In this work we
      present a method based on the photon counting histogram (PCH) analysis, which
      enables the determination of the average number N of molecules within the
      observation volume, for which only the fluorescence of individual molecules is
      detected at a time. Thus, the accurate design of fluorescence fluctuation
      experiments performed in single-molecule detection regime is possible.
      Demonstrative fluorescence fluctuation experiments based on two-photon excitation
      are performed on diluted solutions of coumarin 153, in order to verify the
      potential of the PCH analysis in experiments on the single-molecule detection
      level. If the mean number N of molecules within the excitation volume is larger
      than 0.048, the probability to simultaneously detect the fluorescence of two or
      more molecules is no longer negligible, i.e., no single-molecule detection
      regime. If the mean number N of molecules is lower than 0.0057, the detection
      limit of the method is reached, i.e., the fluorescence signal cannot be
      distinguished from the background. Consequently, the concentration of coumarin
      153 characteristic for the single-molecule detection regime lies in the range 13
      110 pmol/l for the given experimental conditions. We also investigate the
      influence of the molecular brightness, i.e., detected photons per fluorophore
      molecule and sampling time, on the single-molecule detection regime.

PMID- 16613466
TI  - Molecular dynamics study of carbon nanotube oscillators revisited.
AB  - We performed molecular dynamics simulation of double walled carbon nanotube
      (DWCNT) oscillators under constant energy and constant temperatures with various
      commensurations and nanotube lengths. We clarify and resolve questions and
      differences raised by previous simulation results of similar systems. At constant
      energy, sustained oscillation is available for a wide range of initial
      temperatures. But low initial temperature is advantageous for DWCNTs to sustain
      oscillation under constant energy. We observed sustained oscillation at constant
      energy for both commensurate and incommensurate DWCNTs. On the other hand, under
      constant temperatures, both high and low temperatures are disadvantageous to
      sustain DWCNT oscillations. At constant low temperature, neither commensurate nor
      incommensurate DWCNTs can maintain oscillation. At appropriate constant
      temperatures, the oscillatory behavior of incommensurate nanotubes is much more
      sustained than that of commensurate tubes. The oscillatory frequency of DWCNTs
      depends significantly on the length of tubes. The initial oscillatory frequency
      is inversely proportional to the DWCNT lengths. The oscillation frequency of
      DWCNTs is insensitive to the initial temperatures at constant energy, but
      slightly dependent on the temperature at constant temperatures.

PMID- 16613467
TI  - Chain orientation and headgroup structure in Langmuir monolayers of stearic acid
      and metal stearate (Ag, Co, Zn, and Pb) studied by infrared reflection-absorption
      spectroscopy.
AB  - The monolayers of stearic acid at the air-water interface on pure water and ion
      containing subphases have been studied using infrared reflection-absorption
      spectroscopy. In the presence of Co(2+), Zn(2+), and Pb(2+), ordered hydrocarbon
      chains and hexagonal subcell structure remain almost unchanged in comparison with
      those for the monolayer on pure water at the surface pressure of 20 m/Nm. In the
      cases of Co(2+) and Zn(2+), the H-bonded monodentate and unsymmetric bidentate
      chelating structure within the headgroups were formed, and in the case of Pb(2+),
      three types of structures, bidentate chelating, unsymmetric chelating, and
      bidentate bridging coordinations, were formed. The hydrocarbon chains in the
      monolayers are uniaxially oriented at a tilt angle of approximately 0 degrees
      with respect to the surface normal in contrast to a tilt angle of approximately
      20 degrees on pure water surface at 20 m/Nm by the computer simulation of
      theoretical calculation to experimental data. In the presence of Ag(+),
      multilayers were developed with the highly ordered hydrocarbon chains in a
      triclinic subcell structure and a bidentate bridging structure within the
      headgroups. The multilayers were composed of three monolayers and the hydrocarbon
      chains in each monolayer were oriented at an angle of approximately 30 degrees
      away from the surface normal with their C-C-C planes almost perpendicular to the
      water surface.

PMID- 16613468
TI  - The role of excitons' quasiequilibrium in the temperature dependence of the
      poly(9,9-dioctylfluorene) beta phase photoluminescence.
AB  - We investigated the temperature dependence of the poly(9,9-dioctylfluorene) beta
      phase photoluminescence (PL) spectra in spin coated thin films from
      tetrahydrofuran solutions. As the temperature increases from 18 to 300 K a
      continuous blueshift of the 0-0 PL peak of about 25 meV and an increase of the
      peak full width at half maximum (FWHM) of about 49 meV are observed. We show that
      the PL spectra temperature dependence is not due to a temperature dependent
      average conjugation length, as often assumed, but instead it can be
      quantitatively explained in the frame of a thermal quasiequilibrium model for
      excitons in an inhomogeneously broadened excited states distribution. We
      demonstrate that the emission blueshift and broadening are mainly due to the
      increase of the excitons' temperature with the sample one. This effect is
      partially compensated by an increasing efficiency of the exciton energy
      migration. The interplay between these two processes quantitatively explains the
      observed temperature dependence of the PL peak energy and of its FWHM. On the
      contrary we show that the PL spectra are almost independent of the absorption
      blueshift with temperature.

PMID- 16613469
TI  - Surface-enhanced resonance Raman scattering and background light emission coupled
      with plasmon of single Ag nanoaggregates.
AB  - We investigated the optical properties of isolated single aggregates of Ag
      nanoparticles (Ag nanoaggregates) on which rhodamine 6G molecules were adsorbed
      to reveal experimentally a correlation among plasmon resonance Rayleigh
      scattering, surface-enhanced resonance Raman scattering (SERRS), and its
      background light emission. From the lack of excitation-laser energy dependence of
      background emission maxima we concluded that the background emission is
      luminescence, not Raman scattering. The polarization dependence of both SERRS and
      background emission was the same as that of the lowest-energy plasmon resonance
      maxima, which is associated with a longitudinal plasmon. From the common
      polarization dependence, we identified that the lowest-energy plasmon is coupled
      with both SERRS and background emission. In addition, we revealed that the lowest
      energy plasmon with a higher quality factor (Q factor) yields larger SERRS and
      background emission intensity. Also, we identified that the Q factor dependence
      of the SERRS intensity was similar to that of the background emission intensity.
      This similarity directly supported us to demonstrate an enhancement of both SERRS
      and background emission by coupling with a common plasmon radiative mode.

PMID- 16613470
TI  - Density functional calculations of surface free energies.
AB  - We propose a general method of thermodynamic integration to find the free energy
      of a surface, where our integration parameter is taken to be the strain on the
      unit cell of the system (which in the example presented in this paper is simply
      the extension of the unit cell along the normal to the surface), and the
      integration is performed over the thermal average stress from a molecular
      dynamics run. In order to open up a vacuum gap in a continuous and reversible
      manner, an additional control interaction has been introduced. We also use
      temperature integration to find a linear relation for the temperature dependence
      of the free surface energy. These methods have been applied to the titanium
      dioxide (110) surface, using first principles density functional theory. A proof
      of principle calculation for zero temperature shows excellent agreement between
      the integral calculation and the difference in energy calculated by the DFT
      program. Calculations that have been performed at 295 and 1000 K give excellent
      agreement between the two integration methods.

PMID- 16613471
TI  - Electronic structure and excitations in oligoacenes from ab initio calculations.
AB  - Oligoacenes C(4n+2)H(2n+4) (n=2,...,6) are studied using a variety of ab initio
      methods. Density functional theory (DFT) optimized geometries were in good
      agreement with experiment. Vertical and adiabatic ionization potentials and
      electron affinities were computed with DFT and it was found that standard
      exchange-correlation (xc) functionals underestimate ionization potentials in
      oligoacenes. Possible reasons for this underestimation are discussed. Low lying
      electronic excitations were computed using time-dependent density functional
      theory, configuration interaction singles, and configuration interaction singles
      with approximate treatment of doubles. In agreement with earlier work, time
      dependent DFT in conjunction with standard xc-energy functionals substantially
      underestimates the lowest (p) singlet-singlet electronic transition.

PMID- 16613472
TI  - Electrolyte distribution around two like-charged rods: their effective attractive
      interaction and angular dependent charge reversal.
AB  - A simple model for two like-charged parallel rods immersed in an electrolyte
      solution is considered. We derived the three point extension (TPE) of the
      hypernetted chain/mean spherical approximation (TPE-HNC/MSA) and Poisson
      Boltzmann (TPE-PB) integral equations. We numerically solve these equations and
      compare them to our results of Monte Carlo (MC) simulations. The effective
      interaction force, F(T), the charge distribution profiles, rho(el)(x,y), and the
      angular dependent integrated charge function, P(theta), are calculated for this
      system. The analysis of F(T) is carried out in terms of the electrostatic and
      entropic (depletion) contributions, F(E) and F(C). We studied several cases of
      monovalent and divalent electrolytes, for which the ionic size and concentration
      are varied. We find good qualitative agreement between TPE-HNC/MSA and MC in all
      the cases studied. The rod-rod force is found to be attractive when immersed in
      large size, monovalent or divalent electrolytes. In general, the TPE-PB has poor
      agreement with the MC. For large monovalent and divalent electrolytes, we find
      angular dependent charge reversal charge inversion and polarizability. We discuss
      the intimate relationship between this angular dependent charge reversal and rod
      rod attraction.

PMID- 16613473
TI  - Thermodynamics and rheology of cycloolefin copolymers.
AB  - Cycloolefin copolymers of ethylene and norbornene, with norbornene content in the
      range from 36 to 62 mol %, were studied with respect to the thermal,
      thermodynamic, and rheological properties using differential scanning
      calorimetry, pressure-volume-temperature, and dynamic mechanical measurements.
      All copolymers obey the principle of time-temperature superposition, i.e., they
      can be considered as thermorheologically simple except for a temperature range in
      the vicinity of T(g). Despite this, the results on (i) the ratio of activation
      energies E(V)(*)/H(*) used to quantify the origin of the liquid-to-glass
      transition, (ii) the pressure coefficient of the glass temperature T(g)(P), and
      (iii) the dynamic fragility m suggest increasing dynamic heterogeneity with
      increasing norbornene content that is driven by the structural heterogeneity
      along the backbone.

PMID- 16613474
TI  - Aggregation of polyalanine in a hydrophobic environment.
AB  - The dimerization of polyalanine peptides in a hydrophobic environment was
      explored using replica exchange molecular dynamics simulations. A nonpolar
      solvent (cyclohexane) was used to mimic, among other hydrophobic environments,
      the hydrophobic interior of a membrane in which the peptides are fully embedded.
      Our simulations reveal that while the polyalanine monomer preferentially adopts a
      beta-hairpin conformation, dimeric phases exist in an equilibrium between random
      coil, alpha-helical, beta-sheet, and beta-hairpin states. A thermodynamic
      characterization of the dimeric phases reveals that electric dipole-dipole
      interactions and optimal side-chain packing stabilize alpha-helical
      conformations, while hydrogen bond interactions favor beta-sheet conformations.
      Possible pathways leading to the formation of alpha-helical and beta-sheet dimers
      are discussed.

PMID- 16613475
TI  - Stacking fault structure in shear-induced colloidal crystallization.
AB  - We report measurements of the spatial distribution of stacking faults in
      colloidal crystals formed by means of an oscillatory shear field at a particle
      volume fraction of 52% in a system where the pair potential interactions are
      mildly repulsive. Stacking faults are directly visualized via confocal laser
      scanning microscopy. Consistent with previous scattering studies, shear orders
      the initially amorphous colloids into close-packed planes parallel to the
      shearing surface. Upon increasing the strain amplitude, the close-packed
      direction of the (111) crystal plane shifts from an orientation parallel to the
      vorticity direction to parallel the flow direction. The quality of the layer
      ordering, as characterized by the mean stacking parameter, decreases with strain
      amplitude. In addition, we directly observe the three-dimensional structure of
      stacking faults in sheared crystals. We observe and quantify spatial
      heterogeneity in the stacking fault arrangement in both the flow-vorticity plane
      and the gradient direction, particularly at high strain amplitudes (gamma> or
      =3). At these conditions, layer ordering persists in the flow-vorticity plane
      only over scales of approximately 5-10 particle diameters. This heterogeneity is
      one component of the random layer ordering deduced from previous scattering
      studies. In addition, in the gradient direction, the stacking registry shows that
      crystals with intermediate global mean stacking probability are comprised of
      short sequences of face-centered cubic and hexagonal close-packed layers with a
      stacking that includes a component that is nonrandom and alternating in
      character.

PMID- 16613476
TI  - Isotropic-nematic spinodals of rigid long thin rodlike colloids by event-driven
      Brownian dynamics simulations.
AB  - The isotropic-nematic spinodals of solutions of rigid spherocylindrical colloids
      with various shape anisotropies L/D in a wide range from 10 to 60 are
      investigated by means of Brownian dynamics simulations. To make these simulations
      feasible, we developed a new event-driven algorithm that takes the excluded
      volume interactions between particles into account as instantaneous collisions,
      but neglects the hydrodynamic interactions. This algorithm is applied to dense
      systems of highly elongated rods and proves to be efficient. The calculated
      isotropic-nematic spinodals lie between the previously established binodals in
      the phase diagram and extrapolate for infinitely long rods to Onsager's [Ann. N.
      Y. Acad. Sci. 51, 627 (1949)] theoretical predictions. Moreover, we investigate
      the shear induced shifts of the spinodals, qualitatively confirming the
      theoretical prediction of the critical shear rate at which the two spinodals
      merge and the isotropic-nematic phase transition ceases to exist.

PMID- 16613477
TI  - Vibrational excitons in alpha-helical polypeptides: multiexciton self-trapping
      and related infrared transient absorption.
AB  - Based on the multiexciton expansion of a model Hamiltonian, an accurate quantum
      dynamical description of vibrational states formed by amide modes in alpha
      helical polypeptides is presented. Using the multiconfiguration time-dependent
      Hartree method, linear and pump-probe infrared absorption spectra are calculated
      by numerical time propagation of the exciton-chain vibrational wave function. The
      formation of self-trapped exciton states is discussed within the approximation of
      adiabatic excitons and within the full quantum description.

PMID- 16613478
TI  - Facilitated diffusion of DNA-binding proteins: efficient simulation with the
      method of excess collisions.
AB  - In this paper, a new method to efficiently simulate diffusion controlled second
      order chemical reactions is derived and applied to site-specific DNA-binding
      proteins. The protein enters a spherical cell and propagates via two competing
      modes, a free diffusion and a DNA-sliding mode, to search for its specific
      binding site in the center of the cell. There is no need for a straightforward
      simulation of this process. Instead, an alternative and exact approach is shown
      to be essentially faster than explicit random walk simulations. The speed-up of
      this novel simulation technique is rapidly growing with system size.

PMID- 16613479
TI  - Liquid-liquid phase separation and static light scattering of concentrated
      ternary mixtures of bovine alpha and gammaB crystallins.
AB  - We have used light scattering, turbidimetry, and thermodynamic analysis to study
      the phase diagram of concentrated aqueous mixtures of the bovine lens proteins,
      gammaB crystallin, and alpha crystallin. We find that dilute alpha crystallin
      raises the phase separation temperature of concentrated gammaB crystallin, while
      more concentrated alpha crystallin suppresses phase separation. Very concentrated
      alpha/gammaB mixtures can reversibly cloud above 37 degrees C, even though gammaB
      alone phase separates only below temperatures near 0 degrees C, and alpha does
      not phase separate. At the scattering vector magnitude used, high-concentration
      alpha/gammaB mixtures scatter less light than the weighted average of their
      component alpha and gammaB solutions, while low-concentration alpha/gammaB
      mixtures scatter more than such a weighted average. We use a mean-field
      thermodynamic analysis of such ternary mixtures to show that the observed light
      scattering and phase boundaries of alpha and gammaB crystallin mixtures give
      evidence for prominent local fluctuations of relative protein composition. In the
      single phase, these fluctuations scatter comparatively little light, but are
      associated with enhanced thermodynamic instability. By applying this analysis to
      the experimental tie lines we estimate the magnitude of the saddlelike component
      of the free energy near the aqueous-gammaB critical point.

PMID- 16613480
TI  - Paramagnetic relaxation of protons in rotationally immobilized proteins.
AB  - The proton magnetic relaxation dispersion profiles are reported over the proton
      Larmor frequency range from 0.01 to 30 MHz for cross-linked gels and for the dry
      lyophilized bovine serum albumin covalently labeled at lysine with
      diethylenetriaminepentaacetic acid chelates of either Gd(III) or Mn(II) ions. The
      proton spin-lattice relaxation dispersion for the cross-linked paramagnetic
      protein gel is accurately represented as a sum of two major relaxation
      contributions. The diamagnetic term is a power law from the magnetic field
      dependence of the protein protons. The paramagnetic term is approximately
      described by the Solomon-Bloembergen-Morgan class of models. However, the
      paramagnetic relaxation mechanism in the dry lyophilized protein is fundamentally
      different and we develop a new quantitative description of the dispersion
      profile. In the dry case, no peak in the proton relaxation dispersion profile is
      detected from the field dependence of the electron spin relaxation times. The
      high-field paramagnetic relaxation dispersion is a power law in the Larmor
      frequency with an exponent of -0.8, which results from modulation of the electron
      nuclear coupling by the intramolecular dynamics of the protein which primarily
      propagates along the primary structure of the protein. The low-field plateau is
      caused by the interruption of the electron-nuclear spin correlation by electron
      spin relaxation. This new quantitative description provides a simple approach to
      the measurement of electron spin-lattice relaxation times in paramagnetic protein
      systems at room temperature based on the magnetic field dependence of the proton
      spin-lattice relaxation rate constant.

PMID- 16613482
TI  - Comment on "Calculation of nuclear magnetic shieldings using an analytically
      differentiated relativistic shielding formula" [J. Chem. Phys. 123, 114102
      (2005)].

PMID- 16613481
TI  - Optimum folding pathways of proteins: their determination and properties.
AB  - We develop a dynamic optimization technique for determining optimum folding
      pathways of proteins starting from different initial configurations. A coarse
      grained Go model is used. Forces acting on each bead are (i) the friction force,
      (ii) forces from bond length constraints, (iii) excluded volume constraints, and
      (iv) attractive forces between residue pairs that are in contact in the native
      state. An objective function is defined as the total attractive energy between
      nonbonded residues, which are neighbors in the native state. The objective
      function is minimized over all feasible paths, satisfying bond length and
      excluded volume constraints. The optimization problem is nonconvex and contains a
      large number of constraints. An augmented Lagrangian method with a penalty
      barrier function was used to solve the problem. The method is applied to a 36
      residue protein, chicken villin headpiece. Sequences of events during folding of
      the protein are determined for various pathways and analyzed. The relative time
      scales are compared and scaled according to experimentally measured events.
      Formation times of the helices, turn, and the loop agree with experimental data.
      We obtain the overall folding time of the protein in the range of 600 ns-1.2
      micros that is smaller than the experimental result of 4-5 micros, showing that
      the optimal folding times that we obtain may be possible lower bounds. Time
      dependent variables during folding and energies associated with short- and long
      range interactions between secondary structures are analyzed in modal space using
      Karhunen-Loeve expansion.

PMID- 16613484
TI  - Are corals colorful?
AB  - Using in situ spectrometry data and visual system modeling, we investigate
      whether the colors conferred to the reef-building corals by GFP-like proteins
      would look colorful not only to humans, but also to fish occupying different
      ecological niches on the reef. Some GFP-like proteins, most notably fluorescent
      greens and nonfluorescent chromoproteins, indeed generate intense color signals.
      An unexpected finding was that fluorescent proteins might also make corals appear
      less colorful to fish, counterbalancing the effect of absorption by the
      photosynthetic pigments of the endosymbiotic algae, which might be a form of
      protection against herbivores. We conclude that GFP-determined coloration of
      corals may be an important factor in visual ecology of the reef fishes.

PMID- 16613483
TI  - Chromosomal distribution of PcG proteins during Drosophila development.
AB  - Polycomb group (PcG) proteins are able to maintain the memory of silent
      transcriptional states of homeotic genes throughout development. In Drosophila,
      they form multimeric complexes that bind to specific DNA regulatory elements
      named PcG response elements (PREs). To date, few PREs have been identified and
      the chromosomal distribution of PcG proteins during development is unknown. We
      used chromatin immunoprecipitation (ChIP) with genomic tiling path microarrays to
      analyze the binding profile of the PcG proteins Polycomb (PC) and Polyhomeotic
      (PH) across 10 Mb of euchromatin. We also analyzed the distribution of GAGA
      factor (GAF), a sequence-specific DNA binding protein that is found at most
      previously identified PREs. Our data show that PC and PH often bind to clustered
      regions within large loci that encode transcription factors which play multiple
      roles in developmental patterning and in the regulation of cell proliferation.
      GAF co-localizes with PC and PH to a limited extent, suggesting that GAF is not a
      necessary component of chromatin at PREs. Finally, the chromosome-association
      profile of PC and PH changes during development, suggesting that the function of
      these proteins in the regulation of some of their target genes might be more
      dynamic than previously anticipated.

PMID- 16613485
TI  - Photoconvertible fluorescent protein EosFP: biophysical properties and cell
      biology applications.
AB  - EosFP is a fluorescent protein from the coral Lobophyllia hemprichii that changes
      its fluorescence emission from green to red upon irradiation with near-UV light.
      Here we present the spectroscopic properties of wild-type EosFP and a variety of
      monomeric and dimeric mutants and provide a structural interpretation of its
      oligomerization and photoconversion, which is based on X-ray structure analysis
      of the green and red species that we reported recently. Because functional
      expression of the monomeric EosFP variant is limited to temperatures of 30
      degrees C, we have developed a tandem dimer. This construct, in which two EosFP
      subunits are connected by a flexible 12 amino acid linker, expresses well after
      fusion with the androgen and endothelin A receptors at 37 degrees C. A variety of
      applications in cellular imaging, developmental biology and automated high
      content screening applications are presented, which demonstrate that EosFP is a
      powerful tool for in vivo monitoring of cellular processes.

PMID- 16613486
TI  - The 2.0 angstroms crystal structure of a pocilloporin at pH 3.5: the structural
      basis for the linkage between color transition and halide binding.
AB  - The pocilloporin Rtms5 and an engineered variant Rtms5H146S undergo distinct
      color transitions (from blue to red to yellow to colorless) in a pH-dependent
      manner. pK(a) values of 4.1 and 3.2 were determined for the blue (absorption
      lambda(max), 590 nm) to yellow (absorption lambda(max), approximately 453 nm)
      transitions of Rtms5 and Rtms5H146. The pK(a) for the blue-yellow transition of
      Rtms5H146S increased by 1.4 U in the presence of 0.1 M KI, whereas the pK(a) for
      the same transition of Rtms5 was relatively insensitive to added halides. To
      understand the structural basis for these observations, we have determined to 2.0
      angstroms resolution the crystal structure of a yellow form of Rtms5H146S at pH
      3.5 in the presence of iodide. Iodide was found occupying a pocket in the
      structure with a pH of 3.5, forming van der Waals contacts with the tyrosyl
      moiety of the chromophore. Elsewhere, it was determined that this pocket is
      occupied by a water molecule in the Rtms5H146S structure (pH 8.0) and by the side
      chain of histidine 146 in the wild-type Rtms5 structure. Collectively, our data
      provide an explanation for the observed linkage between color transitions for
      Rtms5H146S and binding to halides.

PMID- 16613487
TI  - The role of the protein matrix in green fluorescent protein fluorescence.
AB  - In the ground state of the highly conjugated green fluorescent protein (GFP), the
      chromophore should be planar. However, numerous crystal structures of GFP and GFP
      like proteins have been reported with slightly twisted chromophores. We have
      previously shown that the protein cavity surrounding the chromophore in wild-type
      GFP is not complementary with a planar chromophore. This study shows that the
      crystal structure of wild-type GFP is not an anomaly: most of the GFP and GFP
      like proteins in the protein databank have a protein matrix that is not
      complementary with a planar chromophore. When the pi-conjugation across the
      ethylenic bridge of the chromophore is removed the protein matrix will
      significantly twist the freely rotating chromophore from the relatively planar
      structures found in the crystal structures. The possible consequences of this
      nonplanar deformation on the photophysics of GFP are discussed. A volume analysis
      of the cis-trans-isomerization of HBDI, a GFP chromophore model compound, reveals
      that its hula-twist motion is volume conserving. This means that, if the GFP
      chromophore or GFP chromophore model compounds undergo a cis-trans-isomerization
      in a volume-constricting medium, such as a protein matrix or viscous liquid, it
      will probably isomerize by means of a HT-type motion.

PMID- 16613489
TI  - (Sub)-picosecond spectral evolution of fluorescence in photoactive proteins
      studied with a synchroscan streak camera system.
AB  - The spectral evolution of three photoactive proteins has been investigated by
      measuring the fluorescence with good temporal and wavelength resolution and a
      high signal-to-noise ratio. Upon excitation at 400 nm wild-type (wt) PYP both at
      neutral pH and in the low-pH blueshifted pBdark state exhibited a strong
      quenching of the fluorescence, the major part of which could be described by
      lifetimes of about 1.7 and 7.7 ps. The remaining fluorescence decay occurred
      multiexponentially with lifetimes between 30 and 125 ps. Additionally, in wtPYP
      at neutral pH, a dynamic Stokes shift was found to occur with a time constant of
      about 0.25 ps. In a PYP preparation that was reconstituted with the chromophore 7
      hydroxy-coumarin-3- carboxylic acid rather than the native coumaric acid, and
      which is therefore not capable of performing the cis-trans-isomerization that
      initiates the photocycle in wtPYP, the fluorescence was found to decay
      multiexponentially with lifetimes of 51 ps, 0.33 and 3.77 ns. Additionally,
      dynamic Stokes shifts were observed with time constants of about 0.1 and 3.5 ps.
      Upon comparison of the dynamics of this preparation with that of wtPYP the
      multiexponential decay with lifetimes of 1.7 and 7.7 ps found in wtPYP was
      attributed to photochemistry of the p-coumaric-acid chromophore. The emission
      from bacteriorhodopsin mutant D85S upon excitation at 635 nm decays
      biexponentially with estimated lifetimes of 5.2 and 19.1 ps. No dynamic Stokes
      shift was observed here. Four lifetimes were needed to describe the decay of the
      emission from the A* state in the green fluorescent protein. From a target
      analysis it was concluded that the longer lifetimes are accompanied by a
      decreasing probability of forming I*, which approaches zero with the longest A*
      lifetime of 1.5 ns. These observations may be explained by heterogeneity of A and
      by relaxation of A*. In all three systems studied, multiexponential decay of
      emission was present, suggesting that heterogeneity is a common feature of these
      chromophore protein complexes.

PMID- 16613490
TI  - Penetration of ultraviolet radiation in the marine environment. A review.
AB  - UV radiation (UVR) is a significant ecological factor in the marine environment
      that can have important effects on planktonic organisms and dissolved organic
      matter (DOM). The penetration of UVR into the water column is likely to change in
      the near future due to interactions between global warming and ozone depletion.
      In this study we report underwater instruments employed for the measurement of
      UVR and we review data dealing with the depth of UVR penetration in different
      oceanic areas including the open ocean, Antarctic waters and coastal waters. We
      provide the 10% irradiance depth (Z10%) for UV-A and UV-B as well as for DNA
      damage effective dose (DNA), which we calculated from the values of diffuse
      attenuation coefficients or vertical profiles reported in the literature. We
      observe a clear distinction between open ocean (high Z10%, no variation in the
      ratio UV-B/UV-A), Antarctic waters (increase in the ratio UV-B/UV-A during ozone
      hole conditions) and coastal waters (low Z10%, no variation in the ratio UV-B/UV
      A). These variations in the penetration of UVR could lead to differences in the
      relative importance of photobiological/photochemical processes. We also compare
      in this study the penetration of UV-B (unweighted and weighted by the Setlow
      action spectrum) and DNA damage effective dose.

PMID- 16613491
TI  - Photochemopreventive effect of pomegranate fruit extract on UVA-mediated
      activation of cellular pathways in normal human epidermal keratinocytes.
AB  - UVA is the major portion (90-99%) of solar radiation reaching the surface of the
      earth and has been described to lead to formation of benign and malignant tumors.
      UVA-mediated cellular damage occurs primarily through the release of reactive
      oxygen species and is responsible for immunosuppression, photodermatoses,
      photoaging and photocarcinogenesis. Pomegranate fruit extract (PFE) possesses
      strong antioxidant and anti-inflammatory properties. Our recent studies have
      shown that PFE treatment of normal human epidermal keratinocytes (NHEK) inhibits
      UVB-mediated activation of MAPK and NF-kappaB pathways. Signal transducers and
      activators of transcription 3 (STAT3), Protein Kinase B/AKT and Map Kinases
      (MAPKs), which are activated by a variety of factors, modulate cell
      proliferation, apoptosis and other biological activities. The goal of this study
      was to determine whether PFE affords protection against UVA-mediated activation
      of STAT3, AKT and extracellular signal-regulated kinase (ERK1/2). Immunoblot
      analysis demonstrated that 4 J/cm2 of UVA exposure to NHEK led to an increase in
      phosphorylation of STAT3 at Tyr705, AKT at Ser473 and ERK1/2. Pretreatment of
      NHEK with PFE (60-100 microg/mL) for 24 h before exposure to UVA resulted in a
      dose-dependent inhibition of UVA-mediated phosphorylation of STAT3 at Tyr705, AKT
      at Ser473 and ERK1/2. mTOR, structurally related to PI3K, is involved in the
      regulation of p70S6K, which in turn phosphorylates the S6 protein of the 40S
      ribosomal subunit. We found that UVA radiation of NHEK resulted in the
      phosphorylation of mTOR at Thr2448 and p70S6K at Thr421/Ser424. PFE pretreatment
      resulted in a dose-dependent inhibition in the phosphorylation of mTOR at Thr2448
      and p70S6K at Thr421/Ser424. Our data further demonstrate that PFE pretreatment
      of NHEK resulted in significant inhibition of UVA exposure-mediated increases in
      Ki-67 and PCNA. PFE pretreatment of NHEK was found to increase the cell-cycle
      arrest induced by UVA in the G1 phase of the cell cycle and the expression of Bax
      and Bad (proapoptotic proteins), with downregulation of Bcl-X(L) expression
      (antiapoptotic protein). Our data suggest that PFE is an effective agent for
      ameliorating UVA-mediated damages by modulating cellular pathways and merits
      further evaluation as a photochemopreventive agent.

PMID- 16613492
TI  - Radiation sources providing increased UVA/UVB ratios induce photoprotection
      dependent on the UVA dose in hairless mice.
AB  - In studies involving mice in which doses of UVA (320-400 nm) and UVB (290-320 nm)
      radiation were administered alone or combined sequentially, we observed a
      protective effect of UVA against UVB-induced erythema/edema and systemic
      suppression of contact hypersensitivity. The UVA immunoprotection was mediated by
      the induction of the stress enzyme heme oxygenase-1 (HO-1) in the skin,
      protection of the cutaneous Th1 cytokines interferon-gamma (IFN-gamma) and IL-12
      and inhibition of the UVB-induced expression of the Th2 cytokine IL-10. In this
      study, we seek evidence for an immunological waveband interaction when UVA and
      UVB are administered concurrently to hairless mice as occurs during sunlight
      exposure in humans. A series of spectra providing varying ratios of UVA/UVB were
      developed, with the UVA ratio increased to approximately 3.5 times the UVA
      component in solar simulated UV (SSUV). We report that progressively increasing
      the UVA component of the radiation while maintaining a constant UVB dose resulted
      in a reduction of both the erythema/edema reaction and the degree of systemic
      immunosuppression, as measured as contact hypersensitivity. The UVA-enhanced
      immunoprotection was abrogated in mice treated with a specific HO enzyme
      inhibitor. UVA-enhanced radiation also upregulated the expression of cutaneous
      IFN-gamma and IL-12 and inhibited expression of both IL-6 and IL-10, compared
      with the activity of SSUV. The results were consistent with the previously
      characterized mechanisms of photoprotection by the UVA waveband alone and suggest
      that the UVA component of solar UV may have beneficial properties for humans.

PMID- 16613493
TI  - Determination of the minimum temperature required for selective photothermal
      destruction of cancer cells with the use of immunotargeted gold nanoparticles.
AB  - Laser photothermal therapy of cancer with the use of gold nanoparticles
      immunotargeted to molecular markers on the cell surface has been shown to be an
      effective modality to selectively kill cancer cells at much lower laser powers
      than those needed for healthy cells. To elucidate the minimum light dosimetry
      required to induce cell death, photothermal destruction of two cancerous cell
      lines and a noncancerous cell line treated with antiepidermal growth factor
      receptor (anti-EGFR) antibody-conjugated gold nanoparticles is studied, and a
      numerical heat transport model is used to estimate the local temperature rise
      within the cells as a result of the laser heating of the gold nanoparticles. It
      is found that cell samples with higher nanoparticle loading require a lower
      incident laser power to achieve a certain temperature rise. Numerically estimated
      temperatures of 70-80 degrees C achieved by heating the gold particles agree well
      with the measured threshold temperature for destruction of the cell lines by oven
      heating and those measured in an earlier nanoshell method. Specific binding of
      anti-EGFR antibody to cancerous cells overexpressing EGFR selectively increases
      the gold nanoparticle loading within cancerous cells, thus allowing the cancerous
      cells to be destroyed at lower laser power thresholds than needed for the
      noncancerous cells. In addition, photothermal therapy using gold nanoparticles
      requires lower laser power thresholds than therapies using conventional dyes due
      to the much higher absorption coefficient of the gold nanoparticles.

PMID- 16613494
TI  - Conidial pigmentation is important to tolerance against solar-simulated radiation
      in the entomopathogenic fungus Metarhizium anisopliae.
AB  - The importance of conidial pigmentation to solar UV radiation tolerance in the
      entomopathogenic fungus Metarhizium anisopliae var. anisopliae, was estimated by
      comparing the effects of exposure to simulated solar UV radiation on the wild
      type parent strain U.S. Department of Agriculture (USDA)-Agricultural Research
      Service (ARS) Collection of Entomopathogenic Fungal Cultures (ARSEF) 23, which
      has dark green conidia, and three groups of color mutants with yellow, purple and
      white conidia. The comparisons included inactivation levels and the kinetics of
      germination of conidia exposed or not exposed to simulated solar UV radiation. In
      addition to significantly inactivating the conidia of different mutants, exposure
      to radiation delayed for several hours the germination of surviving conidia of
      the wild type and all mutants. In general, mutants with white conidia were more
      sensitive to simulated solar UV radiation than mutants with purple conidia, which
      were more sensitive than mutants with yellow conidia, which in turn were more
      sensitive than the green wild strain. A significant variation in tolerance to
      simulated solar radiation was observed among mutants within each color group,
      particularly among mutants with yellow conidia. Revertants with green conidia,
      DWR 179 and DWR 176, were obtained from the very sensitive UV mutants DWR 148
      (yellow conidia) and DWR 149 (purple conidia), respectively. These revertants had
      levels of tolerance to simulated solar UV radiation similar to those of the wild
      type ARSEF 23. This observation is strong evidence of the importance of green
      conidial pigmentation for tolerance to simulated solar UV radiation, a factor
      that could be manipulated to produce M. anisopliae strains with more tolerance to
      solar UV radiation.

PMID- 16613495
TI  - Inhibition of UVA-induced c-Jun N-terminal kinase activity results in caspase
      dependent apoptosis in human keratinocytes.
AB  - Inhibition of c-Jun N-terminal kinase (JNK) with the pharmacologic inhibitor
      SP600125 in UVA-irradiated HaCaT cells and human primary keratinocytes resulted
      in dramatic phenotypic changes indicative of cell death. These phenotypic changes
      correlated with caspase 8, 9 and 3 activations as well as cleavage of the caspase
      substrate polyADP-ribose polymerase (PARP). Morphologic analysis and analysis of
      sub-G0 DNA content confirmed apoptotic cell death in these keratinocytes after
      combination treatment. Addition of the general caspase inhibitor zVAD-fmk to
      combination-treated HaCaT cells was able to completely block caspase activation,
      PARP cleavage, the increase in sub-G0 DNA content and the classic morphologic
      features of apoptosis, indicating that this combination treatment resulted in
      caspase-dependent apoptotic cell death. zVAD-fmk treatment of primary
      keratinocytes was able to completely inhibit caspase activation and PARP
      cleavage, reduce morphologic apoptosis at lower concentrations of SP600125 and
      decrease the sub-G(0) DNA content detected after UVA + SP600125 treatment.
      However, cell death and a significant amount of debris was still detected after
      caspase inhibitor treatment, particularly with 125 nM SP600125. At subconfluent
      conditions and low passage, primary keratinocytes were more sensitive to UVA
      irradiation alone than HaCaT cells. In conclusion, we have observed that
      inhibition of UVA-induced JNK activity with the pharmacologic inhibitor SP600125
      resulted in caspase-dependent apoptotic cell death in both the immortalized
      keratinocyte cell line HaCaT and primary keratinocytes. However, the increased
      sensitivity of primary keratinocytes to experimental stress may have also
      resulted in direct cellular injury and caspase-independent cell death.

PMID- 16613496
TI  - In vitro and in vivo inhibition of skin matrix metalloproteinases by Pothomorphe
      umbellata root extract.
AB  - Exposure to UV radiation up-regulates the synthesis of matrix metalloproteinases
      (MMPs), a group of matrix-degrading enzymes. MMPs are regarded as promising
      therapeutic targets and the development of effective inhibitors is an important
      research focus. The plant Pothomorphe umbellata has been shown to exert a potent
      antioxidant activity on the skin and to delay the onset and reduce the incidence
      of UVB-induced chronic skin damage. The aim of the present study was to determine
      the effect of P. umbellata ethanolic root extract on MMP-2 and MMP-9. The in
      vitro inhibition of MMP-2 and MMP-9 was measured by gelatin zymography in the
      presence of different concentrations of P. umbellata extract, as well as in the
      presence of its isolated active principle 4-nerolidylcatechol (4-NC). The
      inhibitory effect of the P. umbellata extract was stronger than that of 4-NC.
      Gelatin zymography and histological analysis revealed that P. umbellata was able
      to inhibit constitutive MMP-9 activity in vivo in mice sacrificed 2 h after UVB
      irradiation. The intensity of the MMP-2 band was unchanged. Our data contribute
      to the elucidation of the mechanism of prevention of photoaging by P. umbellata
      and may provide a rational basis for the use of this plant in prophylaxis against
      and treatment of skin cancer.

PMID- 16613497
TI  - Simultaneous two-photon excitation of photofrin in relation to photodynamic
      therapy.
AB  - Photodynamic therapy (PDT), the use of light-activated drugs (photosensitizers),
      is an emerging treatment modality for tumors as well as various nononcologic
      conditions. Single-photon (1-gamma) PDT is limited by low specificity of the
      photosensitizer, leading to damage to healthy tissue adjacent to the diseased
      target tissue. One solution is to use simultaneous two-photon (2-gamma)
      excitation with ultrafast pulses of near-IR light. Due to the nonlinear
      interaction mechanism, 2-gamma excitation with a focused beam is localized in
      three dimensions, allowing treatment volumes on the order of femtoliters. We
      propose that this will be valuable in PDT of age-related macular degeneration
      (AMD), which causes blindness due to abnormal choroidal neovasculature and which
      is currently treated by 1-gamma PDT. Here, Photofrin has been used as the
      photosensitizer to demonstrate proof-of-principle of 2-gamma killing of vascular
      endothelial cells in vitro. The 2-gamma absorption properties of Photofrin were
      investigated in the 750-900 nm excitation wavelength range. It was shown that 2
      gamma excitation dominates over 1-gamma excitation above 800 nm. The 2-gamma
      absorption spectrum of Photofrin in the 800-900 nm excitation wavelength range
      was measured. The 2-gamma cross section decreased from about 10 GM (1 GM = 10(
      50) cm4 s/photon) at 800 nm to 5 GM at 900 nm. Adherent YPEN-1 endothelial cells
      were then incubated with Photofrin for 24 h and then treated by PDT at 850 nm
      where the 1-gamma contribution was negligible. Cell death was monitored with the
      use of 2-gamma scanning laser microscopy. The light doses required for killing
      were high (6300 J cm(-2) for approximately 50% killing), but 2-gamma cytotoxicity
      was unequivocally demonstrated. Although Photofrin is, per se, not a good choice
      for 2-gamma PDT due to its low 2-gamma cross section, this work provides baseline
      data to guide the development of novel photosensitizers with much higher 2-gamma
      cross sections (>100 GM), which will be required for 2-gamma PDT of AMD (and
      other conditions) to be clinically practical.

PMID- 16613498
TI  - Targeting of sebocytes by aminolevulinic acid-dependent photosensitization.
AB  - Photodynamic therapy using 5-aminolevulinic acid-induced protoporphyrin IX has
      been developed as a very useful therapeutic modality. Recently, several authors
      have reported on the efficacy of this procedure for acne. This approach is based
      on the fact that 5-aminolevulinic acid-induced protoporphyrin IX has strong
      selectivity for sebaceous glands. We used the immortalized human sebaceous gland
      cell line SZ95 to investigate cellular mechanisms of photodynamic therapy using 5
      aminolevulinic acid-induced protoporphyrin IX. Quantification of induced
      protoporphyrin IX production showed dependence on the applied 5-aminolevulinic
      acid dose. When SZ95 sebocytes were differentiated by arachidonic acid treatment,
      there was no difference between them and the control cells with respect to both
      the amount of 5-aminolevulinic acid-induced protoporphyrin IX and the phototoxic
      effects. We altered protoporphyrin IX formation rates by growing cells scattered
      as single cells in the culture dishes. Single cells produced significantly lower
      protoporphyrin IX levels than those grown with intercellular contacts.
      Intracellular localization of protoporphyrin IX was imaged using confocal laser
      scanning microscopy. The differentiation-specific lipid droplets were virtually
      excluded from protoporphyrin IX fluorescence. In addition to weak mitochondrial
      and strong membrane fluorescence, distinctive spots with strong fluorescence were
      observed. These did not colocalize with fluorescent probes for mitochondria,
      lysosomes or the Golgi apparati.

PMID- 16613500
TI  - Photosensitized oxidation and inactivation of pyocyanin, a virulence factor of
      Pseudomonas aeruginosa.
AB  - Pyocyanin (PyO-) (1-hydroxy-5-methylphenazine) is a cytotoxic compound secreted
      by Pseudomonas aeruginosa, an omnipresent bacterium and a human pathogen. We
      report that visible light illumination in the presence of rose bengal, or
      riboflavin, in aerated solutions (pH 7.0-7.2) induces irreversible loss of the
      pigment's characteristic absorption band at 690 nm, indicating its oxidation.
      This photobleaching was paralleled by generation of a multiline Electron
      Paramagnetic Resonance (EPR) spectrum attributed to a PyO(-)-derived radical. The
      reaction was dependent on the presence of air, sensitizers and light, was
      inhibited by sodium azide and was unaffected by ethanol. This suggests that PyO-
      was oxidized largely via singlet oxygen and that hydroxyl radicals were not
      involved. The photochemically modified pigment was less efficient in oxidizing
      NAD(P)H and generated less superoxide (by approximately 50%) than the intact PyO
      , indicating its partial inactivation. 1-Methoxy-5-methylphenazine, a PyO- analog
      in which the -O- moiety was replaced by the methoxy group (-OMe), was resistant
      to oxidation, suggesting that oxidation of PyO- involves its phenolate moiety.
      These results also suggest that photosensitization could be a potentially useful
      method for inactivation of PyO- and, possibly, detoxification of superficial
      wounds (skin, eye) infected with P. aeruginosa.

PMID- 16613499
TI  - Potentiation of the antitumor effect of Merocyanine 540-mediated photodynamic
      therapy by amifostine and amphotericin B.
AB  - Leukemia and lymphoma cells are much more sensitive to Merocyanine 540 (MC540)
      mediated photodynamic therapy (PDT) than normal pluripotent hematopoietic stem
      cells and normal colony forming unit-granulocyte/macrophage progenitors (CFU-GM).
      By contrast, most solid tumor cells are only moderately sensitive to MC540-PDT.
      The limited activity against solid tumor cells has detracted from MC540's appeal
      as a broad-spectrum purging agent. We report here that noncytotoxic
      concentrations of amifostine (Ethyol, Ethiofos, WR-2721) and amphotericin B used
      either alone or in combination potentiate the MC540-sensitized photoinactivation
      of leukemia cells, wild-type small cell lung cancer cells and cisplatin-resistant
      small cell lung cancer cells. Amphotericin B also enhances the MC540-sensitized
      photoinactivation of normal CFU-GM, whereas amifostine protects CFU-GM against
      the cytotoxic action of MC540-PDT. The yield of CD34-positive normal
      hematopoietic stem and progenitor cells is only minimally diminished by
      pretreatment with amifostine, amphotericin B or combinations of amifostine plus
      amphotericin B. Purging protocols that combine MC540-PDT with amifostine or with
      amifostine plus amphotericin B could offer a simple and effective approach to the
      purging of autologous stem cell grafts that are contaminated with solid tumor
      cells or the purging of stem cell grafts from heavily pretreated leukemia
      patients that contain reduced numbers of normal stem and progenitor cells and,
      therefore, can ill afford additional losses caused by purging.

PMID- 16613501
TI  - Antioxidant properties of melanin in retinal pigment epithelial cells.
AB  - The retinal pigment epithelium (RPE) is a monolayer of highly pigmented cells
      lining the inner aspect of Bruch's membrane. This pigmentation is due to
      eumelanin and a possible antioxidant role of melanin is reported here. The photo
      oxidation of A2E, a constituent of RPE lipofuscin, leads to the sequential
      addition of up to nine oxygen atoms and/or the addition or loss of two hydrogen
      atoms. These photo-oxidations were investigated in the presence and absence of
      either calf or human RPE melanin in A2E-laden RPE cells. It was found that calf
      melanin was protective against the photo-oxidation of A2E, with an inhibition of
      oxidation of up to 50% in the case of the addition of two oxygen atoms. Calf
      melanin was also protective against blue light-induced damage to RPE cells. In
      addition this ability appears to decrease in humans as they grow older. With
      aging, a melanin-lipofuscin complex called melanolipofuscin forms. It is
      suggested that the oxidation or photo-oxidation of A2E in vivo may contribute to
      the age-related deterioration of the anti-oxidant role of RPE melanin and lead to
      various retinal disorders, such as age-related macular degeneration.

PMID- 16613502
TI  - Pyrene excimer fluorescence of yeast alcohol dehydrogenase: a sensitive probe to
      investigate ligand binding and unfolding pathway of the enzyme.
AB  - The cysteine residues of yeast alcohol dehydrogenase (YADH) were covalently
      modified by N-(1-pyrenyl) maleimide (PM). A maximum of 3.4 cysteines per YADH
      monomer could be modified by PM. The secondary structure of PM-YADH was found to
      be similar to that of the native YADH using far-UV circular dichroism. The
      covalent modification of YADH by PM inhibited the enzymatic activity indicating
      that the active site of the enzyme was altered. PM-YADH displayed maximum excimer
      fluorescence at an incorporation ratio of 2.6 mol of PM per monomeric subunit of
      YADH. Nucleotide adenine dinucleotide (NAD) divalent zinc and ethanol reduced the
      excimer fluorescence of PM-YADH indicating that these agents induce
      conformational changes in the enzyme. Guanidinium hydrochloride (GdnHCl)-induced
      unfolding of YADH was analyzed using tryptophan fluorescence, pyrene excimer
      fluorescence and enzymatic activity. The unfolding of YADH was found to occur in
      a stepwise manner. The loss of enzymatic activity preceded the global unfolding
      of the protein. Further, changes in tryptophan fluorescence with increasing
      GdnHCl suggested that YADH was completely unfolded by 2.5 M GdnHCl.
      Interestingly, residual structures of YADH were detected even in the presence of
      5 M GdnHCl using the excimer fluorescence of PM-YADH.

PMID- 16613503
TI  - Effect of cloud cover on UVB exposure under tree canopies: will climate change
      affect UVB exposure?
AB  - The effect of cloud cover on the amount of solar UV radiation that reaches
      pedestrians under tree cover was evaluated with a three-dimensional canopy
      radiation transport model. The spatial distribution of UVB irradiance at the base
      of a regular array of spherical tree crowns was modeled under the full range of
      sky conditions. The spatial mean relative irradiance (I(r)) and erythemal
      irradiance of the entire below-canopy domain and the spatial mean relative
      irradiance and erythemal irradiance in the shaded regions of the domain were
      determined for solar zenith angles from 15 degrees to 60 degrees. The erythemal
      UV irradiance under skies with 50% or less cloud cover was not remarkably
      different from that under clear skies. In the shade, the actual irradiance was
      greater under partly cloudy than under clear skies. The mean ultraviolet
      protection factor for tree canopies under skies with 50% or less cloud cover was
      nearly equivalent to that for clear sky days. Regression equations of spatially
      averaged I(r) as a function of cloud cover fraction, solar zenith angle and
      canopy cover were used to predict the variation in erythemal irradiance in
      different land uses across Baltimore, MD.

PMID- 16613504
TI  - Photochemical behavior and Na+,K+-ATPase sensitivity of voltage-sensitive
      styrylpyridinium fluorescent membrane probes.
AB  - RH421 is a widely used voltage-sensitive fluorescent membrane probe. Its exposure
      to continuous illumination with 577 nm light from an Hg lamp leads, however, to
      an increase in its steady-state fluorescence level when bound to lipid membranes.
      The increase occurs on the second time scale at typical light intensities and was
      found to be due to a single-photon excited-state isomerization. Modifications to
      the dye structure are, therefore, necessary to increase photochemical stability
      and allow wider application of such dyes in kinetic studies of ion-transporting
      membrane proteins. The related probe ANNINE 5, which has a rigid polycyclic
      structure, shows no observable photochemical reaction when bound to DMPC vesicles
      on irradiation with 436 nm light. The voltage sensitivity of ANNINE 5 was tested
      with the use of Na+,K+-ATPase membrane fragments. As long as ANNINE 5 is excited
      on the far red edge of its visible absorption band, it shows a similar
      sensitivity to RH421 in detecting charge-translocating reactions triggered by ATP
      phosphorylation. Unfortunately the wavelengths necessary for ANNINE 5 excitation
      are in a region where the Hg lamps routinely used in stopped-flow apparatus have
      no significant lines available for excitation.

PMID- 16613505
TI  - Microwave treatment of eight seconds protects cells of Isatis indigotica from
      enhanced UV-B radiation lesions.
AB  - To determine the role of microwaves in the stress resistance of plants to
      enhanced ultraviolet-B (UV-B) radiation, Isatis indigotica Fort. seeds were
      subjected to microwave radiation for 8 s (wavelength 125 mm, power density 1.26
      mW mm(-2), 2450 MHz). Afterwards they were cultivated in plastic pots in an
      artificial-glass greenhouse maintained at 25 degrees C, 70% relative humidity,
      and 400 micromol mol(-1) CO2, under visible-light conditions of 1500 micromol m(
      2) s(-1) for 8 h day(-1). When the seedlings were 10 days old, they were
      subjected to 10.08 kJ m(-2) UV-B (PAR: 220 micromol m(-2) s(-1)) radiation for 8
      days. Changes in a number of physiological and biochemical characteristics and in
      the thermal decomposition enthalpy of biomass were measured and used as
      indicators of the protective capacity of microwave radiation in this experiment.
      Our results revealed that microwave pretreatment of seeds enhanced UV-B stress
      resistance in the seedlings by decreasing the concentration of malondialdehyde
      (MDA) and increasing the concentration of ascorbic acid (AsA) and UV-B-absorbing
      compounds, increasing the activities of catalase (CAT), peroxidase (POD), and
      superoxide dismutase (SOD), and increasing the energy accumulation of
      photosynthesis. All these results suggest that microwave radiation enhances plant
      metabolism and results in increased UV-B stress resistance. This is the first
      investigation reporting the use of microwave pretreatment to protect the cells of
      Isatis indigotica from UV-B-induced lesions.

PMID- 16613506
TI  - Modified calibration procedures for a Yankee Environmental System UVB-1 biometer
      based on spectral measurements with a brewer spectrophotometer.
AB  - The calibration of the erythemal irradiance measured by a Yankee Environmental
      System (YES) UVB-1 biometer is presented using two methods of calibration with a
      wide range of experimental solar zenith angles (SZAs) and ozone values. The
      calibration is performed through simultaneous spectral measurements by a
      calibrated double-monochromator Brewer MK-III spectrophotometer at "El
      Arenosillo" station, located in southwestern Spain. Because the range of spectral
      measurements of the Brewer spectrophotometer is 290-363 nm, a previously
      validated radiative transfer model was used to account for the erythemal
      contribution between 363 and 400 nm. Both methods are recommended by the World
      Meteorological Organization and we present and discuss here a wide range of
      results and features given by modified procedures applied to these two general
      methods. As is well established, the calibration factor for this type of
      radiometric system is dependent on atmospheric conditions, the most important of
      which are the ozone content and the SZA. Although the first method is insensitive
      to these two factors, we analyze this behavior in terms of the range used for the
      SZA and the use of two different mathematical approaches for its determination.
      The second method shows the dependence on SZA and ozone content and, thus, a
      polynomial as a function of SZA or a matrix including SZA and ozone content were
      determined as general calibration factors for the UV radiometric system. We must
      note that the angular responses of the YES radiometer and Brewer
      spectroradiometer have not been considered, because of the difficulty in
      correcting them. The results show in detail the advantages and drawbacks (and the
      corresponding associated error) given by the different approaches used for the
      determination of these calibration coefficients.

PMID- 16613507
TI  - A five-year study of solar ultraviolet radiation in southern Chile (39 degrees
      S): potential impact on physiology of coastal marine algae?
AB  - This study reports 5 years of (1998-2003) data on continuous solar-irradiation
      measurements from a scanning spectroradiometer (SUV-100) in Valdivia, Chile (39
      degrees S), accompanied by evaluation of the impact of ultraviolet radiation
      (UVR) on marine macroalgae of this site. UVR conditions showed a strong seasonal
      variation, which was less pronounced toward longer wavelengths. Daily maximum
      dose rates (clear days) averaged in winter-summer: UV-B(290-315 nm) 0.30-2.1, UV
      B(290-320 nm) 0.70-3.7, UV-A(315-400 nm) 20.6-62.1, UV-A(320-400 nm) 20.2-60.5 W
      m(-2), and photosynthetically active radiation (PAR) 969-2423 micromol m(-2) s(
      1). The corresponding daily doses (all the days) ranged: UV-B(290-315 nm) 2.6
      40.7, UV-B(290-320 nm) 6.7-78.5, UV-A(315-400 nm) 228-1539, UV-A(320-400 nm) 224
      1501, and PAR 2008-13308 kJ m(-2) d(-1). Taking into consideration action spectra
      of a biological interest, the risk of UV exposure could be up to 37 times higher
      in summer than in winter. The photosynthetic activity (as maximum quantum yield
      of chlorophyll fluorescence, F(v)/F(m)) of the brown alga Lessonia nigrescens
      from the infralittoral zone was markedly more sensitive to UVR than of the green
      alga Enteromorpha intestinalis from the upper midlittoral, and the UV-B wave band
      increased markedly photoinhibition. In L. nigrescens, maximal photoinhibition
      (40%) took place at weighted (the action spectrum for photoinhibition of
      photosynthesis) UVR doses of 800 kJ m(-2), irrespective of the season
      (corresponding midsummer daily dose in Valdivia is 480 kJ m(-2)). In winter, when
      this alga was at its most sensitive, the weighted UV dose causing 35-40%
      photoinhibition was around 200 kJ m(-2). In E. intestinalis, weighted doses of
      800 kJ m(-2) resulted in low photoinhibition (<10 %) and no clear seasonal
      patterns could be inferred. These results confirm that midday summer levels of UV
      B and their daily doses in southern Chile are high enough to produce stress to
      intertidal macroalgae.

PMID- 16613508
TI  - Thioridazine induces immediate and delayed erythema in photopatch test.
AB  - Thioridazine is a phenothiazine derivative that has been used as an
      antipsychotic; it rarely causes photosensitization. However, we noticed that this
      drug induced an erythematous reaction in a photopatch test. Six volunteers were
      patch tested with various concentrations of thioridazine and irradiated with a
      range of UVA doses, and the time courses of the color of and blood flow to the
      test sites were monitored. The free-radical metabolites of thioridazine generated
      under UVA irradiation and its effects on ascorbate radical formation were
      examined with an electron paramagnetic resonance (EPR) spectrometer in vitro. As
      a result, immediate erythema developed during UVA irradiation in most subjects
      when 1% thioridazine was applied for 48 h and irradiation doses were higher than
      4 J cm(-2). Another peak of erythematous reaction was observed 8-12 h after
      irradiation. The in vitro examination detected an apparent EPR signal, which
      appeared when 2 mM thioridazine in air-saturated phosphate buffer was irradiated
      with UVA, whereas this reaction was attenuated under anaerobic conditions. The
      EPR signal of the ascorbate radical was augmented under both aerobic and
      anaerobic conditions. Thioridazine-derived oxidants and/or thioridazine radicals
      generated during UVA irradiation seem to play an important role in this unique
      phototoxic reaction.

PMID- 16613509
TI  - Shiga-like toxin subunit B (SLTB)-enhanced delivery of chlorin e6 (Ce6) improves
      cell killing.
AB  - We used Shiga-like toxin B subunit (SLTB) to deliver the photosensitizer, chlorin
      e6 (Ce6), to Vero cells expressing the Gb3 receptor. Our aim was to provide an
      example of carrier-enhanced photodynamic cell killing with which to start a
      systematic consideration of photosensitizer delivery at the subcellular level.
      SLTB, in contrast to many other potential protein carriers, is delivered
      intracellularly to the Golgi apparatus and endoplasmic reticulum (ER). Ce6 was
      chosen both for its phototoxic properties and its potential for covalent
      conjugation with SLTB. Ce6-SLTB after cleanup contained < or =10% noncovalently
      bound Ce6. The noncovalent binding of porphyrins and chlorins to protein
      conjugates has been well documented, and hence the effective cleanup procedure is
      a significant accomplishment. We demonstrate that Ce6-SLTB enhances delivery of
      Ce6 to target cells as compared to free Ce6. In Vero cells, Ce6-SLTB was over an
      order of magnitude more photodynamically toxic than free Ce6. Moreover, we show
      that in the case of Ce6-SLTB, photosensitizer accumulation is in a combination of
      subcellular sites including mitochondria, Golgi apparatus, ER and plasma
      membrane. The occurrence in nature of diverse B subunit binding sites and the
      possibilities of varied intracellular delivery make optimized use of B subunit
      carriers attractive.

PMID- 16613510
TI  - Mechanism of radical cation formation from the excited states of zeaxanthin and
      astaxanthin in chloroform.
AB  - The C-40 xanthophylls zeaxanthin and astaxanthin were confirmed to form radical
      cations, Car.+, in the electron-accepting solvent chloroform by direct excitation
      using subpicosecond time-resolved absorption spectroscopy in combination with
      spectroelectrochemical determination of the near-infrared absorption of Car.+.
      For the singlets, the S2(1B(u+) state and most likely the S(x)(3A(g)-) state
      directly eject electrons to chloroform leading to the rapid formation of Car.+ on
      a timescale of approximately 100 fs; the lowest-lying S1(2A(g)-) state, however,
      remains inactive. Standard reduction potential for Car.+ was determined by cyclic
      voltametry to have the value 0.63 V for zeaxanthin and 0.75 V for astaxanthin
      from which excited state potentials were calculated, which confirmed the
      reactivity toward radical cation formation. On the other hand, Car.+ formation
      from the lowest triplet excited state T1 populated through anthracene
      sensitization is mediated by a precursor suggested to be a solute-solvent complex
      detected with broad near-infrared absorption to the shorter wavelength side of
      the characteristic Car.+ absorption. However, ground state carotenoids are able
      to react with a secondary solvent radical to yield Car.+, a process occurring
      within 16 micros for zeaxanthin and within 21 mus for astaxanthin. Among the two
      xanthophylls together with lycopene and beta-carotene, all having 11 conjugated
      double bonds, zeaxanthin ranks with the highest reactivity in forming Car.+ from
      either the S2(1B(u+)) or the ground state. The effects of substituent groups on
      the reactivity are discussed.

PMID- 16613511
TI  - Sublethal exposure to UV radiation affects respiration rates of the freshwater
      cladoceran Daphnia catawba.
AB  - We examined the effects of UV radiation (UVR) on metabolic rates of the
      freshwater cladoceran Daphnia catawba. We exposed D. catawba to UVB for 12 h in a
      lamp phototron at levels of 2.08 and 4.16 kJ m(-2) both with and without
      concomitant exposure to UVA and visible photorepair radiation (PRR). We also
      included a group that received PRR only and a dark control group. Respiration
      rates were measured for 6 h following exposure. Respiration rates increased by
      31.8% relative to the dark control at the lowest level of UVB stress (2.08 kJ m(
      2) UVB with PRR), whereas respiration was inhibited by 70.3% at the highest
      stress level (4.16 kJ m(-2) UVB without PRR). Survival rates in the group that
      received PRR only and the group exposed to 2.08 kJ m(-2) and PRR were not
      significantly different from that in the control group; however, the survival
      rate was reduced for all other UVR exposures. We hypothesize that enhanced
      respiration rates reflect energetic costs related to repair of cellular
      components damaged by sublethal levels of UVR. Increases in respiration rate of
      the magnitude we found in our experiment could significantly reduce energetic
      reserves available for growth and reproduction, especially in cases where these
      costs are incurred repeatedly during a series of days with high levels of UVR.

PMID- 16613512
TI  - Determination of photo-oxidation products within photoyellowed bleached wool
      proteins.
AB  - Photo-oxidative processes occurring in wool can lead to significant
      photoyellowing of the fiber. In particular, wool that has been chemically
      bleached photoyellows more rapidly and to a greater degree than untreated wool.
      Direct identification of the chromophores responsible for such yellow
      discoloration in irradiated wool has proven to be elusive for many years. This
      article describes the characterization and location of yellow photo-oxidation
      products within the proteins of photoyellowed bleached wool fabric, using
      advanced protein chemistry techniques. The discolored fabric was enzymatically
      digested and chromatographed by high-pressure liquid chromatography, with
      monitoring at 400 nm, to select out fractions containing yellow chromophoric
      species. Thorough tandem mass spectrometric analysis was then used to sequence
      peptides and, in turn, to characterize modifications to key amino acid residues
      that had resulted in yellow chromophore formation. In total, 11 separate yellow
      chromophoric species were identified, ten derived from tryptophan residues and
      one from tyrosine. The tryptophan-derived modifications characterized included
      hydroxytryptophan, N-formylkynurenine, hydroxyformylkynurenine, kynurenine,
      hydroxykynurenine, carbolines, tryptophandiones and nitrotryptophan. The tyrosine
      derived modification of tyrosine to dopa was also identified. The range of
      photomodifications we observed provides insight into the photo-oxidation pathways
      occurring within irradiated fibrous proteins leading to the formation of yellow
      chromophores.

PMID- 16613513
TI  - Role of complement anaphylatoxin C3a in photodynamic therapy-elicited engagement
      of host neutrophils and other immune cells.
AB  - Tumor treatment by photodynamic therapy (PDT) provokes a host-protective
      inflammatory and acute-phase response and an immune reaction. Neutrophilia
      manifested in this context is driven by multiple mediators of neutrophil
      chemotaxis orchestrated by an activated complement system. Mouse FsaR
      fibrosarcoma was used in this study to further investigate neutrophilia induced
      by Photofrin-based PDT. The complement anaphylatoxin C3a was identified as a
      major chemoattractant in the advanced phase of PDT-induced neutrophilia, because
      injecting mice with antibodies blocking its receptor C3aR significantly inhibited
      the increase in neutrophil levels 8 h after PDT. At the same time point, an
      increased C3aR expression was detected in neutrophils, monocytes and B
      lymphocytes in the blood of host mice. Peritoneal macrophages and mast cells
      harvested from treatment-naive mice exhibited elevated C3aR expression after
      coincubation in vitro for 8 h with PDT-treated FsaR cells. Thus, C3a emerges as
      one of the key effector molecules engaged in PDT-induced host response.

PMID- 16613514
TI  - Tetrakis(4-pyridyl)porphyrin supramolecular complexes with cyclodextrins in
      aqueous solution.
AB  - The formation of inclusion complexes of hydroxypropyl-beta-cyclodextrin,
      heptakis(2,6-di-O-methyl)-beta-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-beta
      cyclodextrin with 5,10,15,20-tetrakis(4-pyridyl)porphyrin (TpyP) has been studied
      in aqueous buffer solution (phosphate buffer pH = 7 and I = 0.01 M) to give a
      structural and spectroscopic characterization of a new class of potential
      sensitizers for photodynamic therapy. The interaction was investigated by a
      combination of UV/Vis absorption, fluorescence anisotropy, time-resolved
      fluorescence and circular dichroism. The experimental results point to the
      presence of the pigment in water in a monomeric complexed form. The fluorescence
      anisotropy measurements suggest that TpyP forms 1:1 complexes with heptakis(2,3,6
      tri-O-methyl)-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, while 1:2
      complexes are obtained with heptakis(2,6-di-O-methyl)-beta-cyclodextrin.

PMID- 16613515
TI  - Prevention of UV radiation-induced premature skin aging in hairless mice by the
      novel compound Melanocin A.
AB  - Repetitive exposure of the skin to UV radiation induces various harmful changes,
      such as thickening, wrinkle formation, inflammation and carcinogenesis. A variety
      of natural compounds and synthetic compounds have been studied to determine
      whether they can prevent UV-induced harmful effects. In this study, we
      investigated the effect of a novel compound, Melanocin A, which was isolated from
      Eupenicillium shearii F80695, on UV-induced premature skin aging. First, we
      studied the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9
      expression in an immortalized human keratinocyte cell line, HaCaT, in vitro.
      Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels
      and Melanocin A suppressed this expression in a dose-dependent manner. We then
      investigated the effect of Melanocin A on UV-induced skin changes in hairless
      mice in vivo. Chronic exposure of hairless mouse dorsal skin to UV increased skin
      thickness and induced wrinkle formation and the gelatinase activities of MMP-2
      and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic
      skin changes and MMP-2 and MMP-9 expression. Taken together, these results show
      that Melanocin A can prevent the harmful effects of UV that lead to skin aging.
      Therefore, we suggest that Melanocin A should be viewed as a potential
      therapeutic agent for preventing and/or treating premature skin aging.

PMID- 16613516
TI  - A Web-based tool for UV irradiance data: predictions for European and Southeast
      Asian sites.
AB  - There are a range of UV models available, but one needs significant pre-existing
      knowledge and experience in order to be able to use them. In this article a
      comparatively simple Web-based model developed for the SoDa (Integration and
      Exploitation of Networked Solar Radiation Databases for Environment Monitoring)
      project is presented. This is a clear-sky model with modifications for cloud
      effects. To determine if the model produces realistic UV data the output is
      compared with 1 year sets of hourly measurements at sites in the United Kingdom
      and Thailand. The accuracy of the output depends on the input, but reasonable
      results were obtained with the use of the default database inputs and improved
      when pyranometer instead of modeled data provided the global radiation input
      needed to estimate the UV. The average modeled values of UV for the UK site were
      found to be within 10% of measurements. For the tropical sites in Thailand the
      average modeled values were within 1120% of measurements for the four sites with
      the use of the default SoDa database values. These results improved when
      pyranometer data and TOMS ozone data from 2002 replaced the standard SoDa
      database values, reducing the error range for all four sites to less than 15%.

PMID- 16613517
TI  - Bioluminescence color modulation of Vibrio fischeri strain Y1 coupled with
      alterable levels of endogenous yellow fluorescent protein and its fluorescence
      imaging.
AB  - Bioluminescence (BL) (lambda(max) approximately 535 nm) of Vibrio fischeri strain
      Y1 has been previously characterized in terms of the fluctuation in intracellular
      levels of yellow fluorescent protein (YFP). In this study fluorescence
      microscopic analysis has revealed that yellow fluorescence, as well as blue
      fluorescence attributable to a luciferase intermediate, is localized to the
      periphery of V. fischeri Y1 cells. This finding indicates that both YFP and the
      luciferase are present in the vicinity of the cell membrane. By using cyanide to
      enhance yellow BL, it has been shown that BL modulation is coupled with the
      fluctuations in the intracellular levels of YFP and the primary emitter. On the
      basis of the BL characterization, combined with results of a sedimentation
      experiment, it has been shown that larger cells produce a relatively stronger
      yellow BL. Two-dimensional gel electrophoresis of cell-protein extracts has shown
      that the YFP level is more alterable than the luciferase level. It is postulated
      that the yellow BL modulation takes place in connection with cell growth.

PMID- 16613518
TI  - Enhanced acidity, photophysical properties and liposome binding of
      perfluoroalkylated phthalocyanines lacking C-H bonds.
AB  - The acid-base, spectroscopic, photophysical and liposome-binding properties of
      the recently synthesized free base, 29H,31H,1,4,8,11,15,18,22,25-octafluoro
      2,3,9,10,16,17,23, 24-octakisperfluoro(isopropyl) phthalocyanine, F64PcH2, are
      reported. The perfluoroalkylation of the phthalocyanine core renders the hydrogen
      atoms acidic, with a pK(a) = 6. The F64Pc(-2) dianion is detected already at pH
      3, by singular-value decomposition analysis of electronic spectra. F64Pc(-2)
      generates 1O2 with quantum yields phi(delta) = 0.252 (in MeOH) and 0.019 in
      liposomes. Metallation of the Pc macrocycle to yield F64PcZn increases phi(delta)
      to 0.606 and 0.126 in MeOH and liposomes, respectively. Surprisingly, F64Pc(-2)
      (but not F64PcH2 or F64PcZn) binds strongly to liposomes, with a binding constant
      K(b) = 25 (mg/mL)(-1). The fully protonated F64PcH2, but not the zwitterionic
      F64Pc(-2), might favor hydrogen bonding, thus reducing its lipophilicity.
      Similarly, the Lewis acidity of Zn in F64PcZn, and thus its ability to bind water
      within a hydrophobic perfluoroalkyl pocket, is significantly enhanced by the
      fluorinated substituents.

PMID- 16613519
TI  - DH-I-180-3-mediated photodynamic therapy: biodistribution and tumor vascular
      damage.
AB  - An important goal of photodynamic therapy (PDT) for treatment of various cancers
      is to shorten PDT-performing time and simultaneously enhance PDT efficacy. Here,
      we investigated the nontumor tissue distribution of and the tumor vascular damage
      caused by a new photosensitizer, DH-I-180-3, in mice with implanted EMT6 mammary
      tumor cells. In addition, we performed cell-based assays to evaluate the basic
      antitumor effect of DH-I-180-3/PDT in EMT6 cells. After administration of PDT,
      the type of cell death was characterized to be apoptosis, and a change in the
      mitochondrial membrane potential was also observed within minutes. On the other
      hand, tumor growth was remarkably retarded in vivo in mice that received DH-I-180
      3/PDT, compared with mice in the control group, which were exposed to light
      irradiation alone. Finally, tumors in some mice nearly healed. The antitumor drug
      reached a maximum concentration approximately 3 h after administration. However,
      PDT was most effective when there was substantial accumulation of DH-I-180-3 in
      the tumor vasculature and in healthy tissue. The histological demonstration
      provided further evidence of tumor vascular damage. On the basis of these
      findings, we suggest that PDT with the photosensitizer DH-I-180-3 induces
      vascular damage with blood vessel shutdown, in addition to direct killing of
      tumor cells, in mice.

PMID- 16613520
TI  - Interspecific variation in UV defense mechanisms among temperate freshwater
      fishes.
AB  - An important step in predicting the effects of future increases in UV radiation
      (UVR) is to evaluate the mechanisms that organisms use to prevent and repair DNA
      damage and determine how those mechanisms influence UVR sensitivity. Damage is
      prevented to varying degrees through photoprotection and repaired via two main
      pathways: nucleotide excision repair and photoenzymatic repair. At present,
      little is known about the generality or similarity of these defenses among
      temperate freshwater fishes. We used laboratory experiments to compare UVR
      defense mechanisms among five freshwater fish species representing four families
      and three orders. Purified DNA, freeze-killed larvae and live larvae were exposed
      to UVB radiation for 12 h in the presence or absence of photorepair radiation.
      After exposure, we quantified frequencies of cyclobutane pyrimidine dimers in
      each exposure treatment. All five species used photoprotection and proportional
      decreases in dimer frequency were similar for all species. Evidence of excision
      repair was also found for all species but proportional decreases in photoproduct
      frequencies varied among species. Finally, evidence of photoenzymatic repair was
      found for only two of the five species.

PMID- 16613521
TI  - The iodide/iodate actinometer in UV disinfection: determination of the fluence
      rate distribution in UV reactors.
AB  - Thirty-seven Suprasil quartz spheres, each approximately 1 cm in diameter and
      containing an iodide-iodate actinometric solution, were attached to a metal rack
      and inserted into a bench-scale UV reactor filled with water. The spheres were
      located at various distances and heights around a 12.4 W low-pressure Hg lamp
      housed inside a 3.2 cm-radius quartz sleeve in the middle of an annular batch
      reactor. UV light exposure at 254 nm was performed with the percent transmittance
      of the water present in the reactor at either 73% or 100% defined over a 1 cm
      path length. The spheres were simultaneously exposed to the UV light for a given
      period of time, after which the solutions were removed from the spheres and the
      yield of triiodide determined from the increase in absorbance at 352 nm. The
      resulting fluence rate at each site was then calculated on basis of the yield of
      triiodide. These results were compared with the predictions of a mathematical
      model based on the multiple point source summation approximation, including
      reflection and refraction at the air-quartz-water interface. Initially, the
      agreement was not satisfactory, especially in regions at an oblique angle to the
      lamp. The model was modified from a multiple point source model to a multiple
      cylindrical segment model by incorporating a cosine factor. The agreement between
      the new model and the experimental data was excellent and these experiments
      provide a strong validation of the model, even under conditions in which the
      fluence rate varied by >1000-fold between extreme sites in the reactor.

PMID- 16613522
TI  - Novel porphyrin conjugates with a potent photodynamic antitumor effect:
      differential efficacy of mono- and bis-beta-cyclodextrin derivatives in vitro and
      in vivo.
AB  - In the present study we investigated the photosensitizing properties of two novel
      mono- and bis-cyclodextrin tetrakis (pentafluorophenyl) porphyrin derivatives in
      several tumor cell lines and in BALB/c mice bearing subcutaneously transplanted
      syngeneic mouse mammary carcinoma 4T1. Both studied sensitizers were localized
      mainly in lysosomes and were found to induce cell death by triggering apoptosis
      in human leukemic cells HL-60. In 4T1 and other cell lines both apoptotic and
      necrotic modes of cell death occurred depending on drug and light doses. Mono
      cyclodextrin porphyrin derivative P(beta-CD)1 exhibited stronger in vitro
      phototoxic effect than bis-cyclodextrin derivative P(beta-CD)2. However, in vivo
      P(beta-CD)2 displayed faster tumor uptake with maximal accumulation 6 h after
      application, leading to complete and prolonged elimination of subcutaneous tumors
      within 3 days after irradiation (100 J cm(-2)). In contrast, P(beta-CD)1 uptake
      was slower (48 h) and the reduction of tumor mass was only transient, reaching
      the maximum at the 12 h interval when a favorable tumor-to-skin ratio appeared.
      Thus, P(beta-CD)2 represents a new photosensitizing drug displaying fast and
      selective tumor uptake, strong antitumor activity and fast elimination from the
      body.

PMID- 16613524
TI  - The photochemistry of a bis-crown ether based on benzobis(thiazole) and its
      alkaline earth metal cation complexes.
AB  - Irradiation of acetonitrile solutions of the bis-crown ether E,E-2,7-bis[2
      (6,7,9,10,12,13,15,16-octahydro-5,8,11,14,17-pentaoxabenzocyclopentadecen-2
      yl)vinyl]-benzo[1,2-d;3,4-d']bisthiazole (hereafter, 1) gives efficient E --> Z
      photoisomerization (initial phi(trans --> cis) = 0.48), leading to lambda(exc)
      dependent quasi-photostationary states composed primarily of E,Z and E,E isomer
      mixtures. Further irradiation gives [2 + 2]-cycloadducts of 1. In the presence of
      Ba2+ ions, essentially quantitative formation of 2:2 complexes, 1(2) x (Ba2+)2
      controls the photochemical outcome. E --> Z photoisomerization of the ligand is
      entirely suppressed and efficient intramolecular [2 + 2]-photocycloaddition in
      the complexes leads to cyclobutane dimers of 1 (phiCB = 0.26). The reactivity of
      1 in the presence of Mg2+ ions for which 1:2 complex formation dominates gives
      both cis-trans photoisomerization and enhanced photocycloaddition.

PMID- 16613525
TI  - Ozone and UV radiation over southern South America: climatology and anomalies.
AB  - Ozone and UV radiation were analyzed at eight stations from tropical to sub
      Antarctic regions in South America. Ground UV irradiances were measured by
      multichannel radiometers as part of the Inter American Institute for Global
      Change Radiation network. The irradiance channels used for this study were
      centered at 305 nm (for UV-B measurements) and 340 nm (for UV-A measurements).
      Results were presented as daily maximum irradiances, as monthly averaged, daily
      integrated irradiances and as the ratio of 305 nm to 340 nm. These findings are
      the first to be based on a long time series of semispectral data from the
      southern region of South America. As expected, the UV-B channel and total column
      ozone varied with latitude. The pattern of the UV-A channel was more complex
      because of local atmospheric conditions. Total column ozone levels of < 220
      Dobson Units were observed at all sites. Analysis of autocorrelations showed a
      larger persistence of total column ozone level than irradiance. A decreasing
      cross-correlation coefficient between 305 and 340 nm and an increasing cross
      correlation coefficient between 305 nm and ozone were observed at higher
      latitudes, indicating that factors such as cloud cover tend to dominate at
      northern sites and that ozone levels tend to dominate at southern sites. These
      results highlight the value of long-term monitoring of radiation with
      multichannel radiometers to determine climatological data and evaluate the
      combination of factors affecting ground UV radiation.

PMID- 16613526
TI  - BPH: epidemiology and comorbidities.
AB  - Recently published data suggest that clinical benign prostatic hyperplasia (BPH),
      which is hallmarked by the occurrence of moderate-to-severe lower urinary tract
      symptoms (LUTS), occurs in about one quarter of men in their 50s, one third of
      men in their 60s, and about half of all men 80 years or older. Although effective
      treatments for LUTS/BPH are available, this condition often occurs in the context
      of common, age-related comorbidities such as cardiovascular disease,
      hypertension, and erectile dysfunction. Alpha1-selective adrenergic receptor (a1
      AR) antagonists (eg, alfuzosin, doxazosin, tamsulosin, terazosin) remain the
      cornerstone of therapy for LUTS/BPH. In addition, 5-alpha-reductase inhibitors
      (ie, dutasteride, finasteride) have been associated with improvements in LUTS/BPH
      in men with larger prostates, especially when used in combination with a1-AR
      antagonists. Although all these drugs have been shown to be beneficial for the
      treatment of BPH, there are differences in side-effect profiles. When selecting
      an appropriate course of therapy, these side effects and any impact they may have
      on existing comorbid conditions must be considered.

PMID- 16613527
TI  - Treatment and pharmacologic management of BPH in the context of common
      comorbidities.
AB  - Benign prostatic hyperplasia (BPH) is extremely common in the aging man and may
      cause significant lower urinary tract symptoms (LUTS) necessitating treatment.
      Drug treatment is the mainstay of treatment for symptomatic BPH and is directed
      at relaxing prostatic smooth muscle, reducing prostate volume, or a combination
      of these effects. The most commonly used drugs for this indication are alpha1
      adrenergic receptor antagonists, which relax prostatic smooth muscle, and 5-alpha
      reductase inhibitors, which reduce prostatic androgen levels and consequently
      prostate size. Invasive interventions include the gold standard, transurethral
      resection of the prostate (TURP), and several minimally invasive surgical
      options. Although effective in alleviating symptoms, TURP carries a higher risk
      of morbidity and complications, including sexual side effects (mainly ejaculatory
      dysfunction), than medical therapy or minimally invasive techniques. Treatment
      for BPH, whether medical or surgical, must take patients' comorbid conditions
      into consideration so that LUTS may be effectively relieved, with the smallest
      risk of exacerbating any concomitant conditions.

PMID- 16613529
TI  - The great debate part II: should managed care rely on cost sharing to manage big
      ticket biologics?

PMID- 16613528
TI  - BPH: costs and treatment outcomes.
AB  - The current treatments for benign prostatic hyperplasia (BPH) include
      pharmacotherapy with alpha1-selective adrenergic receptor (a1-AR) antagonists, 5
      alpha-reductase inhibitors (5-aRIs), and a range of invasive and minimally
      invasive interventions, each of which is effective in the amelioration of lower
      urinary tract symptoms (LUTS) and the prevention of symptom progression and BPH
      related complications. Pharmacotherapy is considered the mainstay of treatment
      for LUTS caused by BPH. The available a1-AR antagonists have comparable efficacy
      for the relief of LUTS and to enhance patients' quality of life. The use of
      nonsubtype-selective drugs in this class may precipitate vasodilatory adverse
      events such as dizziness, somnolence, and orthostatic hypotension. Based on
      current studies, a1-AR antagonists are more cost effective (particularly the
      subtype-selective a1-AR antagonist, tamsulosin) than the 5-aRIs (eg, finasteride)
      and comparable in cost to transurethral resection of the prostate and minimally
      invasive therapies. There are few cost-effectiveness studies comparing the
      various pharmacologic interventions for BPH. Only 1 cost-analysis model has
      addressed the impact of adverse events on the cost effectiveness of
      pharmacotherapy for BPH. The publication of additional analyses would contribute
      to the appropriate selection of therapy in patients with BPH.

PMID- 16613530
TI  - The case for cost sharing for biologic therapies.

PMID- 16613531
TI  - The case against excessive cost sharing.

PMID- 16613532
TI  - Balancing quality employee benefits with cost sharing.

PMID- 16613533
TI  - On the prevalence of familial nonmedullary thyroid cancer in multiply affected
      kindreds.
AB  - Clinical and genetic studies of familial nonmedullary thyroid cancer (FNMTC) have
      yielded conflicting results concerning the aggressiveness of the tumors, and
      uncertainty of their genetic makeup. In most reports of multiply affected
      families, the composition of the kindreds has favored families of 2 affected
      members. Using data for differentiated thyroid cancer (DTC) provided by the
      Surveillance Epidemiology and End Results (SEER) branch of the National Cancer
      Institute, and fine-needle aspiration data from Mayo Clinic, I found that the
      likelihood of 2 cases of sporadic DTC (RR) in a 9-member first-degree family was
      1.25% of all DTC families, amounting to 39.4% of 306 multi-hit families reported
      in the literature. To study the remaining affected families I used the Bernouilli
      trials model of exact probability. The 60.6% of non-RR, multiply affected
      families are mostly concentrated in kindreds of 2 to 5 affected members. In 2-hit
      families, 62%-69% of affected members are sporadic (RR) cases. In families having
      3 or more affected members, fewer than 6% have 1 or more sporadic (R) cases, and
      fewer than 0.15% have 2 or more. In families of 3 to 5 affected members, more
      than 96% of affected members have the familial (F) trait. Approximately 1 of 338
      DTC cases carries the F-trait. Since approximately 40% of multiply affected
      member first-degree kindreds of DTC, and a significant majority of 2-hit
      families, are composed of clinically evident, sporadic cases only clinical and
      genetic investigations of FNMTC should center on families of 3 or more affected
      members.

PMID- 16613534
TI  - The wind of change in the therapy of lung cancer.

PMID- 16613536
TI  - Role of efaproxiral in metastatic brain tumors.
AB  - Brain metastases from breast cancer are common and cause significant morbidity
      and mortality. Treatment with whole-brain radiotherapy provides a median survival
      of only 4-6 months. One mechanism affecting sensitivity to radiation is tumor
      oxygenation. Hypoxic tumor cells are more likely to be resistant to radiation and
      adversely affect prognosis. For nearly 70 years, all attempted modalities have
      failed to circumvent tumor hypoxia and increase tumor death. Abraham and
      colleagues developed a fibric acid derivative that would cause the displacement
      of oxygen from hemoglobin and improve tissue oxygenation. After modifications to
      enhance absorption into the red blood cell, RSR13 (efaproxiral) was developed.
      Efaproxiral was found to be safe and improved tumor oxygenation in preclinical
      studies. Early Phase I and II trials supported the earlier preclinical evidence
      while demonstrating that efaproxiral was safe and effective. A randomized Phase
      III study, Radiation Enhancing Allosteric Compounds of Hypoxic brain metastases
      (REACH, RT-009), failed to show a significant improvement in overall survival in
      all eligible patients treated with efaproxiral and whole-brain radiation.
      However, there was a statistically significant improvement in median survival and
      quality of life within a subset of metastatic breast cancer patients. Efaproxiral
      is currently being studied with radiotherapy in a confirmatory trial in the
      treatment of brain metastases from breast cancer. Furthermore, the combination of
      efaproxiral with radiotherapy is being investigated in other solid tumors.

PMID- 16613537
TI  - Clinical experiences with G17DT in gastrointestinal malignancies.
AB  - The development of new agents for the treatment of gastrointestinal malignancies
      is increasing in pace and importance. The discovery of novel targets, namely the
      epidermal growth factor receptor and vascular endothelial growth factor, have
      sparked an explosion of new agents being tested in gastrointestinal malignancies.
      Clearly, novel agents and approaches are required. G17DT is a novel
      immunoconjugate designed to elicit a humoral response against the N-terminal end
      of G17 gastrin. In this overview, the authors summarize the clinical research
      focused on gastrointestinal tract cancers to date. In total, there is a clear
      signal of efficacy with this compound, although further testing is required in
      order for this efficacy to be demonstrated in a manner that will support
      regulatory approval.

PMID- 16613538
TI  - Treatment of primary intraocular melanoma.
AB  - The treatment of intraocular melanoma has evolved recently. Enucleation has been
      superseded largely by brachytherapy, proton beam radiotherapy, stereotactic
      irradiation, trans-scleral local resection, transretinal resection and diode
      laser phototherapy. Many patients develop metastatic disease, which usually
      involves the liver and occurs hematogenously. Disseminated disease rarely
      responds to therapy, and is usually fatal within 1 year of the onset of symptoms.
      Uveal melanomas develop characteristic chromosomal abnormalities, such as loss of
      chromosome 3. This is associated with a reduction in the 5-year survival from
      approximately 95% to less than 50%.

PMID- 16613539
TI  - Protective effects of green tea against prostate cancer.
AB  - Prostate cancer has the third highest incidence of all cancers in men worldwide
      with incidence and mortality being particularly high in affluent, developed
      countries. Tea, especially green tea, has demonstrated promise in the prevention
      of several cancers. Green tea contains several components including catechins, a
      category of polyphenols that have chemopreventive properties. Although evidence
      from epidemiological studies is not comprehensive, it is strengthened by animal
      and in vitro evidence suggesting that consumption of tea is associated with
      decreased risk or progression of prostate cancer. Emerging evidence and potential
      biological mechanisms for the role of green tea in prostate cancer prevention are
      presented in this review.

PMID- 16613540
TI  - Regulation of the G1/S phase of the cell cycle and alterations in the RB pathway
      in human lung cancer.
AB  - The retinoblastoma (RB)-Cyclin (CCN)D1-p16 cell cycle pathway has a crucial role
      in lung tumorigenesis. Impairment of the RB pathway has been shown to occur in
      almost all lung tumors. A deregulation at any level of this core RB pathway seems
      to make cells insensitive to the mitogenic signaling that is required for cell
      cycle progression. To date, almost all participants in this pathway have been
      shown to be altered to a various degree in lung tumors. Some of the alterations
      are mutually exclusive, including RB and p16INK4A . In small cell lung cancer,
      the RB tumor suppressor gene is inactivated in almost 90% of the tumors, whereas
      in non-small cell lung cancer, the cyclin-dependent kinase (CDK)4 inhibitor
      p16INK4A is inactivated in 40-60% of the tumors. Many mechanisms may be
      responsible for activating the RB-Cyclin D1 pathway, including activating (CDK4)
      and inactivating mutations (p16INK4A ), deletions (RB and p16INK4A ),
      amplifications (CCND1 and CDK4), silencing methylation (p16INK4A and RB), and
      hyper-phosphorylation (RB). As some of these alterations, such as p16INK4A
      methylation, can also be detected in bronchial lavage and serum, they could
      potentially serve as useful markers for the early detection of lung cancer. This
      review summarizes recent experiments describing the variable roles of key-player
      molecules of the RB pathway and different mechanisms by which the RB pathway can
      be altered in lung cancer.

PMID- 16613541
TI  - The effect of chemotherapy on symptom control and quality of life in patients
      with advanced non-small cell lung cancer.
AB  - Differences in survival outcomes with various treatments for advanced non-small
      cell lung cancer are very modest. Despite this, end points looking at the
      patients' subjective benefit, such as symptom control, quality of life or
      clinical benefit, have only been sparsely implemented into clinical trials as
      primary points of interest. This review focuses on available evidence regarding
      these patients' subjective end points in recent clinical trials. Compared with
      best supportive care, chemotherapy offers symptom control, not only in patients
      with objective response to chemotherapy, but also in a proportion of patients
      with disease stabilization. However, interpretation of quality-of-life objectives
      is more difficult, owing to several methodological problems, but improvement in
      various domains of quality of life is also reported. Different treatment options,
      such as older platinum-based schedules, modern platinum-based doublets, single
      agent treatment with a new drug or nonplatinum-based doublets, are
      comprehensively reviewed. Future randomized studies should take up the challenge
      of looking at the patients' benefit as a primary end point.

PMID- 16613542
TI  - Clinical trials of antiangiogenic therapy in non-small cell lung cancer: focus on
      bevacizumab and ZD6474.
AB  - Lung cancer is the leading cause of cancer deaths in the USA. Despite the
      development of new chemotherapy regimens, the prognosis remains poor. Several
      studies comparing various platinum-based regimens failed to produce a significant
      impact in the outcomes for patients with non-small cell lung cancer and this
      therapeutic modality appears to be reaching a plateau. It has become clear that
      further advances will require the addition of agents with a different mechanism
      of action. Bevacizumab is the antiangiogenic agent at the most advanced stage of
      development in the treatment of cancer. Bevacizumab is synergistic with
      chemotherapy and usually well tolerated. The addition of bevacizumab to
      chemotherapy improved survival in patients with metastatic non-small cell lung
      cancer in a randomized clinical trial. Several small molecule antiangiogenic
      agents are in development. In this article, currently available data from
      clinical trials of antiangiogenic compounds in advanced non-small cell lung
      cancer are reviewed.

PMID- 16613543
TI  - Recent trends and future perspectives in isolated hepatic perfusion in the
      treatment of liver tumors.
AB  - Isolated hepatic perfusion (IHP) involves a method of complete vascular isolation
      of the liver to enable treatment of liver tumors with high drug doses without
      systemic toxicity. Recent clinical studies have mainly employed IHP with
      melphalan with or without tumor necrosis factor-alpha and mild hyperthermia. The
      results of these studies demonstrate that high response and survival rates can be
      achieved with IHP. The current status, recent developments and future
      perspectives of IHP are discussed in this review.

PMID- 16613544
TI  - Liver resection in the treatment of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is a leading cause of cancer death worldwide. Liver
      resection and liver transplantation remain the only options for cure. Since the
      indications for orthotopic liver transplantation are limited, partial liver
      resection is the more common treatment. Recently, indications for liver resection
      have been expanded and there have been advances in the associated surgical
      techniques. This review describes the state-of-the-art of liver resection for
      hepatocellular carcinoma. Topics covered include: new indications, such as
      treatment of large tumors, bilobar tumors and those associated with vascular
      invasion; preoperative assessment of liver function; and surgical strategies. An
      overview of the most common staging systems, which are useful in predicting
      prognosis after liver resection for hepatocellular carcinoma, is given.

PMID- 16613545
TI  - Cancer of the esophagus: the value of preoperative patient assessment.
AB  - In the past few years, major improvements and new technologies have been proposed
      and applied in esophageal surgery. Its evolution depended not only on a thorough
      knowledge of surgical anatomy and technique, but also on important developments
      in pre- and postoperative care. 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. The surgeon-related
      factors are surgical experience, hospital volume and multidisciplinary approach.
      Preoperative evaluation is defined as the process of clinical assessment that
      precedes the delivery of anesthesia. The principle is to gain information
      concerning patients that leads to modification of their management, and improves
      the outcome from surgery.

PMID- 16613546
TI  - Management of prostate cancer. Part 2: localized and locally advanced disease.
AB  - Prostate cancer is the most prevalent nondermatological malignancy affecting men
      in the Western world. An increase in public awareness has led to earlier
      detection. Accepted treatments for localized prostate cancer include active
      surveillance, radical prostatectomy, interstitial brachytherapy, external beam
      radiotherapy and watchful waiting. The authors discuss the rationale for the
      different approaches together with outcomes including toxicity. Novel approaches
      are also explored. The management of locally advanced disease has long been a
      challenge and the evolving evidence is reviewed.

PMID- 16613547
TI  - Electron intraoperative treatment in patients with early-stage breast cancer:
      data update.
AB  - Intraoperative radiotherapy is a technique where a high, single-fraction
      radiation dose is delivered directly to the tumor bed during a surgical
      procedure, after the removal of a neoplastic mass, with minimal exposure of
      surroundings tissues, which are displaced and shielded during the procedure.
      Intraoperative radiotherapy has been used in the treatment of various
      malignancies, mostly in combination with external beam radiation therapy. The
      long-term results suggest a positive impact on local controls that appear to be
      associated with increased survival. Modern intraoperative radiotherapy can be
      performed either with electron beams or photons, and has been used recently in
      early-stage cancer as a boost or as an exclusive treatment, especially for breast
      tumors, with extremely promising results. The results of different clinical
      studies have demonstrated the feasibility of the technique and it is expected
      that its application will become more widespread in the immediate future.
      Intraoperative electron radiotherapy in the treatment of initial-stage breast
      cancer may be an excellent alternative to external beam radiation therapy in an
      appropriate selected group of patients. However, intensive long-term follow-up is
      required for a better evaluation of local control and possible side effects.

PMID- 16613548
TI  - Second-line treatment of postmenopausal women with advanced breast carcinoma.
AB  - Breast cancer is the most prevalent cancer in women and, currently, there is no
      standard of care for the treatment of metastatic disease. Treatment options are
      based on a number of tumor- and patient-related factors. This review explores
      some of these options, including the use of hormonal manipulation in the
      treatment of hormone-positive disease, current chemotherapy options and the use
      of targeted therapies, such as trastuzumab.

PMID- 16613549
TI  - Positron emission tomography: clinical applications in oncology. Part 2.
AB  - This review continues from a previous review on this topic, which was published
      in the December issue. In that review, the role of positron emission tomography
      in lung cancer, lymphoma, breast cancer, head and neck cancer, gastroesophageal
      cancer, colorectal cancer, malignant melanoma, bone tumors and ovarian cancer was
      discussed. In this review, the role of positron emission tomography in other
      malignancies, such as gynecological malignancies other than ovary, pancreatic
      cancer, hepatocellular cancer, gastrointestinal tumors, urological malignancies,
      neuroendocrine tumors, adrenocortical tumors, soft-tissue sarcomas, pituitary and
      brain tumors, is discussed.

PMID- 16613551
TI  - Dopamine receptor pharmacology: interactions with serotonin receptors and
      significance for the aetiology and treatment of schizophrenia.
AB  - The classification of dopamine receptors proposed more than two decades ago
      remains valid today. Based on biochemical and pharmaceutical properties two main
      classes of dopamine receptors can be distinguished: D(1)-like (D(1), D(5)) and
      D(2)-like (D(2), D(3), and D(4)) dopamine receptors. Dopamine receptors belong to
      the class of G protein-coupled receptors and signal to a wide range of membrane
      bound and intracellular effectors such as ion channels, secondary messenger
      systems and enzymes. Although the pharmacological properties of ligands for D(1)
      like and D(2)-like dopamine receptors are quite different, the number of
      selective ligands for each of the five receptors subtypes is rather small. Many
      drugs used to treat neurological and neuropsychiatric disorders like Parkinson's
      disease, restless leg syndrome and schizophrenia have affinities for dopamine
      receptors. Such medications are not without limitations so the development of
      novel (selective or aselective) dopamine receptor ligands is of the utmost
      importance for improved therapeutic approaches for these diseases. In that
      respect it is also important to understand how dopamine receptor ligands affect
      receptor signalling processes such as desensitization, receptor
      heterodimerization and agonist-receptor trafficking, issues which will be
      discussed in the present review. Furthermore, attention is paid to interactions
      of dopamine receptors with serotonin receptors since many drugs used to treat
      above mentioned disorders of the brain also possess affinities for serotonin
      receptors. Because of the enormity of this area we have tried to focus more
      specifically on interactions within the prefrontal cortex where it appears that
      the serotonergic modulation of dopaminergic function might be very relevant to
      schizophrenia.

PMID- 16613552
TI  - The dopamine D3 receptor: a therapeutic target for the treatment of
      neuropsychiatric disorders.
AB  - The role of the D(3) receptor has remained largely elusive before the development
      of selective research tools, such as selective radioligands, antibodies, various
      highly specific pharmacological agents and knock-out mice. The data collected so
      far with these tools have removed some of the uncertainties regarding the
      functions mediated by the D(3) receptor. The D(3) receptor is an autoreceptor
      that controls the phasic, but not tonic activity of dopamine neurons. The D(3)
      receptor, via regulation of its expression by the brain-derived neurotrophic
      factor (BDNF), mediates sensitization to dopamine indirect agonists. This process
      seems responsible for side-effects of levodopa (dyskinesia) in the treatment of
      Parkinson's disease (PD), as well as for some aspects of conditioning to drugs of
      abuse. The D(3) receptor mediates behavioral abnormalities elicited by
      glutamate/NMDA receptor blockade, which suggests D(3) receptor-selective
      antagonists as novel antipsychotic drugs. These data allow us to propose novel
      treatment options in PD, schizophrenia and drug addiction, which are awaiting
      evaluation in clinical trials.

PMID- 16613553
TI  - Molecular biology, pharmacology and functional role of the plasma membrane
      dopamine transporter.
AB  - The plasma membrane dopamine transporter (DAT) tightly regulates the
      extracellular concentrations of dopamine (DA) by re-capturing released
      neurotransmitter back into the presynaptic neuronal terminals and/or neighboring
      DA projections thereby providing an effective way to regulate synaptic and
      extrasynaptic DA levels. This transporter is a primary target of many potent
      psychotropic drugs and neurotoxins, such as cocaine, amphetamines and 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this review we summarize recent
      advances in understanding the structure, regulation, and functional roles of DAT
      in normal DA physiology and pathological conditions, such as attention deficit
      hyperactivity disorder (ADHD) and neurodegenerative processes, as well as their
      contribution to the pharmacology of psychostimulant drugs. Significant new
      insights on these issues have been gained using mice with genetic deletion of
      DAT.

PMID- 16613554
TI  - Targeting exocytosis: ins and outs of the modulation of quantal dopamine release.
AB  - Dopaminergic neurotransmission is mediated by the vesicular release of dopamine
      (DA), i.e. DA exocytosis. DA exocytosis and its modulation are generally believed
      to affect neuronal communication, development, maintenance and survival, and
      contribute to extracellular DA levels in the brain. As a result, DA exocytosis
      likely plays an important role in several neurological and psychiatric disorders,
      like Parkinson's disease (PD) and schizophrenia. As exocytosis is part of a
      sophisticated ensemble of processes, it can be modulated at different levels,
      including DA synthesis, uptake and vesicular transport as well as Ca(2+)
      homeostasis and exocytotic proteins. Nonetheless, to be effective, modulation of
      exocytosis should result in functional changes, which are reflected by changes in
      release frequency, vesicle contents, and the time course of the exocytotic event.
      As will be shown in this review, functional changes in DA exocytosis can be
      produced by e.g. pharmacological/drug treatment, feedback mechanisms and up/down
      regulation of exocytosis-related proteins. Moreover, the mode of DA exocytosis,
      i.e. classical full fusion or kiss-and-run exocytosis, could also serve as a
      potential target for functional modulation of dopaminergic neurotransmission.
      Since the onset and progression of neurological and psychiatric disorders often
      show a strong correlation with changes in brain DA levels, DA synthesis,
      transport or uptake, the findings described in this review highlight the
      importance of the modulation of (the mode of) DA exocytosis for normal
      progression of dopaminergic neurotransmission and the potential of exocytotic
      processes as drug targets.

PMID- 16613555
TI  - Excitability of dopamine neurons: modulation and physiological consequences.
AB  - This aim of this chapter is to review literature on the excitability and function
      of dopamine neurons that originate in the midbrain and project to cortico-limbic
      and motor structures (A9 and A10 dopamine pathways). Electrophysiological studies
      on rodent or non-human primates have shown that these dopamine neurons are silent
      or spontaneously active. The spontaneously active neurons show slow regular
      firing, slow irregular firing or fast bursting activity. In the first section, we
      will review how neuronal firing is modulated by intrinsic factors, such as
      impulse-regulating somatodendritic dopamine autoreceptors, a balance between
      inward voltage-gated sodium and calcium currents and outward potassium currents.
      We will then review the major excitatory and inhibitory pathways that play
      important roles in modulating dopamine cell excitability. In the second section,
      we will discuss how, in addition to being modulated by intrinsic and synaptic
      factors, excitability of dopamine neurons can also be modulated by life
      experiences. Dopamine neurons change their firing rate throughout the
      developmental period, their activity can be modified by stressful life events,
      and the firing mode can change as a consequence of acute or repeated exposure to
      psychoactive drugs. Finally, these cells change their firing pattern in response
      to behaviorally relevant stimuli and learning experiences. We will conclude by
      discussing how changes in the physiology of the dopamine neurons could
      participate in the development or exacerbation of psychiatric conditions such as
      drug addiction.

PMID- 16613556
TI  - Phasic dopamine signaling during behavior, reward, and disease states.
AB  - The neurotransmitter dopamine is important in reward processing, however its
      precise modulatory role is still being investigated. Carbon-fiber microelectrodes
      can be used to monitor dopamine on a subsecond time scale in the striatum and
      nucleus accumbens of rats during behavior, and this approach is providing new
      insights into the mechanisms that control its extracellular concentration as well
      as the conditions under which it is released. Three main processes govern the
      amount of dopamine measured extrasynaptically: exocytotic release, neuronal
      uptake, and diffusion away from the release site. By monitoring local
      extracellular dopamine concentrations in the striatum following electrical
      stimulation of dopamine-containing neurons, release, uptake and diffusion can be
      individually examined and quantified. Dopaminergic neurons have been shown to
      fire in two firing modes, tonic and bursts at higher frequency. Electrical
      stimulation can be designed to mimic either mode to examine their effects on
      dopamine release. Burst firing causes a transient increase in extracellular
      dopamine while tonic firing causes a new steady-state level. In behaving
      primates, dopaminergic neurons display short-latency, phasic firing to primary
      reward and conditioned cues associated with reward. These bursts code differences
      between actual and predicted rewards. In rats, transient dopamine release in
      terminal regions that mimics that seen during burst firing has been demonstrated
      during reward-related cues. Taken together, these studies indicate that phasic
      dopamine release is a critical mediator of reward-related processes.

PMID- 16613557
TI  - Dopamine and the diseased brain.
AB  - Dysfunction of central dopaminergic neurotransmission has been implicated in a
      series of neuropsychiatric disorders, including Tourette's syndrome,
      schizophrenia, and drug and alcohol dependence. The behavioral and
      psychopathological manifestations of central dopaminergic dysfunction differ
      depending on the site of their neurobiological correlate. These sites may be
      found in the dorsal or ventral striatum, but also in cortical regions such as the
      limbic and prefrontal cortex, among other locations. A low basic dopamine
      turnover and an increase in the availability of dopamine D2 receptors in the
      caudate body have been associated with the severity of motor tics in Tourette's
      syndrome. In the ventral striatum and particularly in the nucleus accumbens,
      different drugs of abuse stimulate dopamine release and thus reinforce drug
      consumption. The downregulation of dopamine D2 receptors in this area of the
      brain has been associated with alcohol craving and an increase in the processing
      of alcohol-related stimuli in the medial prefrontal cortex. Brain imaging studies
      in which intrasynaptic dopamine release is manipulated in vivo have shown that
      increased subcortical dopamine release is associated with the pathogenesis of
      positive symptoms in schizophrenia. This review discusses a broad range of brain
      imaging and neuroendocrinological studies on dopaminergic dysfunction in
      neuropsychiatric disorders, including relevant findings on the basis of primate
      studies. In addition, the hypothesis is examined that phasic dopamine release is
      associated with salience attribution to external stimuli, insofar as it mediates
      reward anticipation in the ventral striatum and limbic cortex, habit formation in
      the dorsal striatum, and working memory function in the prefrontal cortex.

PMID- 16613558
TI  - Future directions for allergen immunotherapy.

PMID- 16613559
TI  - Modified recombinant allergens for safer immunotherapy.
AB  - Molecular cloning and recombinant production of allergens offered new
      perspectives for the increasing problem of allergies. A variety of preparations
      are being developed aiming to increase safety and improve efficacy of specific
      immunotherapy. Recombinant-based approaches are mostly focused on genetic
      modification of allergens to produce molecules with reduced allergenic activity
      and conserved antigenicity, i.e. hypoallergens. Studies dealing with genetic
      modifications of allergen genes reported the production of site-directed mutants,
      deletion mutants, allergen fragments and oligomers, and allergen chimeras. An
      alternative to genetic engineering is the chemical modification of pure
      recombinant allergens. It has been shown that allergens modified with
      immunostimulatory DNA sequences (allergen-ISS conjugates), which masks IgE
      epitopes and adds a desirable Th1-inducing character to the allergen molecule.
      Other chemical modifications include oligomerization by aldehydes (allergoids)
      and maleylation, which seems to target allergens to particular antigen presenting
      cells. Several of these modified allergen preparations have been already
      evaluated for their safety in clinical provocation studies. So far, clinical
      trials showed the efficacy and safety of immunotherapy with an Amb a 1-ISS
      conjugate for ragweed pollen-allergic patients. In addition, a preparation
      consisting of hypoallergenic fragments of Bet v 1 was evaluated for immunotherapy
      of birch pollen-allergic patients. In parallel, several animal studies have now
      demonstrated the potential of genetic immunization for allergy treatment in the
      future.

PMID- 16613560
TI  - Immunological mechanisms of specific allergen immunotherapy.
AB  - Allergy is an immunological disorder, which is driven by uncontrolled allergen
      activated T cell subsets, leading to immediate type hypersensitivity against
      otherwise harmless environmental allergens. These allergens are tolerated by
      healthy individuals as well as by patients, who successfully underwent allergen
      specific immunotherapy (SIT). The successful SIT is characterized by the
      induction of T cell unresponsiveness against the given allergen. Regulatory T
      cells (Tregs), which are installed or enhanced by SIT and govern the activity of
      potentially pro-allergic effector T cells, mediate this unresponsiveness. The
      current article reviews the mechanisms underlying the balance of these cell
      populations along with suppressive mechanisms of SIT, which may serve as future
      drug targets.

PMID- 16613561
TI  - Immunotherapy for food allergy.
AB  - The past two decades have witnessed an increase in prevalence of food allergy
      that has been matched with a tremendous progress in research that has led to
      better understanding of pathogenic mechanisms and development of novel therapies
      for food allergy. Establishment of murine models of peanut and cow's milk allergy
      has been extremely useful in investigating food allergy treatments. Diverse
      strategies for prevention and treatment of established food allergy are being
      evaluated. Anti-IgE antibody therapy, Chinese herbal medicines, and killed
      bacteria expressing modified major peanut allergens represent the most promising
      approaches that will lead to development of therapy for patients for whom no
      effective treatment is currently available.

PMID- 16613562
TI  - Information management for the study of allergies.
AB  - Microarrays and other large-scale screening technologies produce quantities of
      increasingly complex allergy data. These data link molecular and clinical
      measurements and observations and provide fertile ground for improving our
      understanding of the processes involved in allergic reactions. Information
      technology is employed in gathering, storage, retrieval and analysis of these
      data. The increasing proportion of allergy data are generated from genomics and
      proteomics approaches. The major activity focuses on characterization of
      allergens including IgE reactivity, structural properties, and mapping of IgE and
      T-cell epitopes. Because of the complexity of allergy data, their utilization
      requires bioinformatics approaches. Allergen data are stored in the general and
      specialist databases. At least a dozen of important allergen databases and data
      repositories have been developed to date. These data are analysed using general
      and specialist bioinformatics tools. The major applications of bioinformatics
      include support for allergen characterization, assessment of allergenicity, and
      identification of allergic cross-reactivity. These applications in turn support
      the development of vaccines and therapies for allergic disease. In this article
      we review allergen databases and tools for the analysis of allergens, and discuss
      the new directions in the field supported by large scale screening involving
      genomics, proteomics, and bioinformatics support.

PMID- 16613563
TI  - Non-injection routes for allergen immunotherapy: focus on sublingual
      immunotherapy.
AB  - Allergen specific immunotherapy, together with drugs and allergen avoidance, is a
      cornerstone in the management of respiratory allergy. The non-injection or local
      routes were developed with the main goal of improving the safety and minimizing
      the risk of those side effects, which can accompany the injection route. The pure
      oral route and the bronchial route showed, in the clinical trials, only a
      marginal efficacy with not negligible side effects. Therefore, these routes are
      no longer recommended for clinical use. The nasal route proved effective and
      safe, but its efficacy is strictly limited to the nose. Moreover, the practical
      problems with administration have made the use of nasal immunotherapy
      progressively declining. The efficacy of the sublingual route is confirmed by
      numerous controlled trials, and a meta analysis (in allergic rhinitis). The
      safety profile, as derived from clinical trials and post marketing surveillance
      studies, is satisfactory, with mild gastrointestinal complaints being the more
      frequent side effect reported. Recent studies have also demonstrated that SLIT
      has a long-lasting effect and a preventive effect on the onset of new skin
      sensitizations, and interesting data on adherence and mechanisms of action have
      become recently available. Based on these experimental data, SLIT is now
      officially accepted as a viable alternative to the subcutaneous route in adults
      and children. Several points still need to be elucidated, including: mechanisms
      of action, optimal dosages, and indications in pediatric patients.

PMID- 16613564
TI  - Recombinant expression systems for allergen vaccines.
AB  - Allergen immunotherapy of future is likely to be based on allergy vaccines that
      contain engineered allergens modified to abolish or substantially reduce their
      IgE-binding activity in order to remove the risk of unwanted anaphylactic
      responses. The development of efficient systems for the production of recombinant
      allergens in sufficient quantities is requirement for establishing use of
      engineered allergens as components of allergy vaccines. This review outlines
      relative advantages and disadvantages of various heterologous systems for
      production of recombinant allergens. Microbial systems are most convenient and
      cost effective platforms for the production of recombinant allergens. However,
      lack of post-translational processing implies that some allergens have to be
      expressed in eukaryotic systems for proper folding and post-translational
      modifications such as glycosylation. Yeast systems can yield high levels of
      recombinant allergens but often are associated with hyper- glycosylation
      problems. Mammalian cell culture systems offer suitable post -translational
      modifications but are nearly hundred fold more expensive than microbial systems.
      The use of plants as bio-factories for production of recombinant allergens is
      emerging as a very attractive option as plants-based production system offer
      several advantages over other expression systems such as post translational
      processing of proteins, low production costs, scale up ability and enhanced
      safety due to absence of animal or human pathogens.

PMID- 16613565
TI  - Current options in the treatment of mast cell mediator-related symptoms in
      mastocytosis.
AB  - Patients with mastocytosis have symptoms related to the tissue response to the
      release of mediators from mast cells (MC), local mast cell burden or associated
      non-mast cell hematological disorders. MC contain an array of biologically active
      mediators in their granules, which are preformed and stored. MC are also able to
      produce newly generated membrane-derived lipid mediators and are a source of
      multifunctional cytokines. Mediator-related symptoms can include pruritus,
      flushing, syncope, gastric distress, nausea and vomiting, diarrhea, bone pain and
      neuropsychiatric disturbances; these symptoms are variably controlled by adequate
      medications. Management of patients within all categories of mastocytosis
      includes: a) a careful counseling of patients (parents in pediatric cases) and
      care providers, b) avoidance of factors triggering acute mediator release, c)
      treatment of acute and chronic MC-mediator symptoms and, if indicated, d) an
      attempt for cytoreduction and treatment of organ infiltration by mast cells.

PMID- 16613567
TI  - Lipid mediators: lipoxin and aspirin-triggered 15-epi-lipoxins.
AB  - Lipoxins (LX) and their 15-epimers, aspirin triggered lipoxins (ATL) are emerging
      as major promoters of resolution of the inflammatory reaction. These eicosanoids,
      that carry a tetraene chromophore, derive from sequential lipoxygenase (LO)
      metabolism of arachidonic acid. Three principal routes of LX/ATL biosynthesis
      have been uncovered. One involves cooperation between 15- and 5-LO, one other
      requires interactions between 12- and 5-LO and a third is characterized by 5-LO
      transformation of intermediary products generated by aspirin-acetylated
      cyclooxygenase (COX)-2. Thus, in a large majority of cases the biosynthesis of
      these eicosanois requires transcellular metabolic exchange during cell-cell
      interactions. LX and ATL are rapidly metabolized and inactivated by monocyte 15
      hydroxyprostaglandin dehydrogenase (PGDH). A number of stable analogs that resist
      inactivation and retain biological activity has been synthesized. Accumulating
      evidence suggests that these analogs may have a potential therapeutic impact in a
      variety of diseases characterized by neutrophil-mediated persistent inflammation,
      such as reperfusion injury, gastro-intestinal and renal inflammatory disorders,
      periodontitis. Clinical evaluation of LXA4 and 15-epi-LXA4 formation and their
      pharmacological regulation may be now achieved using recently developed ELISA
      assays, that allow large-scale measurements in human biological fluids.

PMID- 16613568
TI  - Lipoxin and synthetic lipoxin analogs: an overview of anti-inflammatory functions
      and new concepts in immunomodulation.
AB  - Lipoxin A4 (LXA4) and lipoxin B4 (LXB4) were first identified in 1984 by Serhan
      and colleagues as 5- and 15-lipoxygenase interaction products of activated
      leukocytes. Endogenous transcellular biosynthesis of LXA4 and LXB4 occurs via
      interaction of leukocytes with epithelium, endothelium or platelets. Acetylation
      of cyclooxygenase-2 (COX-2) by aspirin can trigger 15-epi-LXA4 (ATL)
      biosynthesis. Elucidating the pharmacological actions of lipoxins and ATL was
      facilitated by total synthesis of LXA4 in 1988 by Nicolaou and colleagues. In
      1994, Fiore and colleagues used [3H]-LXA4 to identify the cDNA for a human G
      protein-coupled, high affinity LXA4 and ATL receptor (ALX-R/FPRL-1), providing
      the first hints for the molecular basis of lipoxin actions. The recognition that
      lipoxins and ATL undergo rapid, prostaglandin dehydrogenase (PGDH)-mediated
      metabolic inactivation led do the design and synthesis of first-generation PGDH
      resistant LXA4, LXB4 and ATL analogs in 1995-1998 by Serhan, Petasis and
      colleagues. These relatively stable pharmacological agents, together with myeloid
      specific ALX-R-expressing transgenic mice, have provided powerful tools to
      explore lipoxin functions in vivo. Here we briefly review the substantial body of
      evidence supporting the lipoxin --> ALX-R pathway as a novel and potent mechanism
      for preventing/resolving acute inflammation. Emphasis will also be placed on
      recent findings that lipoxins play new roles in "immunomodulation" via regulation
      of macrophage, dendritic cell, and T-lymphocyte effector functions in the setting
      of polarized T-helper cell responses (Th1 and Th2). These studies suggest roles
      for lipoxins as novel regulators of allergy and adaptive immunity and that
      lipoxins may have therapeutic potential in chronic immune disorders.

PMID- 16613569
TI  - Novel aspects of annexin 1 and glucocorticoid biology: intersection with nitric
      oxide and the lipoxin receptor.
AB  - This review will emphasize the concept of anti-inflammation and propose that
      better understanding of the resolution phase of the inflammatory response
      organized by the host against inflammatory insults can lead to the identification
      of novel targets for drug development. Under the umbrella of anti-inflammation,
      we discuss here recent discoveries in the biology of annexin 1 and
      glucocorticoids. The fact that annexin 1 and another anti-inflammatory mediator,
      lipoxin A4, converge onto a specific membrane receptor (termed ALX) might help
      understanding the resolution phase of inflammation, and strengthen the use of
      this target for innovative drug development. In addition, glucocorticoids (GC),
      historically linked to annexin 1, are widely use in the clinical control of
      several pathologies with an inflammatory etiology, though their use is often
      burdened by several side effects. The development of new GC with more specific or
      improved mechanisms, e.g. the nitro-steroids, would go along this wave and,
      potentially, could be of large applicability. The two mediators/targets here
      illustrated are to be taken as examples of the clues that the study of anti
      inflammation might give to the pharmaceutical industry for innovative drug
      discovery.

PMID- 16613570
TI  - Nitric oxide and inflammation.
AB  - There are several pre-clinical studies on the involvement of NO in inflammation.
      From this large amount of information it is clear that virtually every cell and
      many immunological parameters are modulated by NO. Thus, the final outcome is
      that NO cannot be rigidly classified as an anti-inflammatory or pro-inflammatory
      molecule. This peculiar aspect of the pathophysiology of NO has hampered the
      development of new drugs based on the concepts developed. Recent therapeutic
      approach are targeted to increase endogenous NO by activating the gene and some
      promising early data are available. At the present stage one of the most
      promising approach in the inflammation field is represented by a new class of NO
      releasing compounds namely NO-NSAIDs that have recently enrolled in phase 2
      clinical studies.

PMID- 16613572
TI  - Nitric oxide, aspirin-triggered lipoxins and NO-aspirin in gastric protection.
AB  - The use of nonsteroidal anti-inflammatory drugs is associated with an incidence
      of severe gastrointestinal adverse events of 2-4%, the most common of which is
      bleeding. These events are largely attributable to the ability of these drugs to
      suppress prostaglandin and thromboxane synthesis. Prostaglandins perform a number
      of important functions in the gastrointestinal tract, particularly with respect
      to resistance of the mucosa to injury. Nitric oxide also appears to be a key
      mediator of gastrointestinal mucosal defence, and this has been exploited in the
      development of a novel class of anti-inflammatory drugs, called "NO-NSAIDs",
      which exhibit little if any gastrointestinal toxicity. NO-NSAIDs are more
      effective than traditional NSAIDs in reducing pain and inflammation. Another
      class of inflammatory mediators that contribute to gastrointestinal mucosal
      defence are the lipoxins. These products of arachidonic acid metabolism can
      increase the resistance of the stomach to the damaging effects of aspirin.
      Indeed, aspirin can trigger the formation of a lipoxin by the stomach which acts
      to diminish the damaging effects of this drug. Lipoxins and nitric oxide are
      important mediators of mucosal defence in the stomach (and elsewhere in the
      gastrointestinal tract) and represent attractive therapeutic targets for reducing
      the incidence of gastric ulceration.

PMID- 16613571
TI  - NO-NSAIDs: from inflammatory mediators to clinical readouts.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase (COX)-2
      selective inhibitors (COXIBs) are widely used drugs. However, their use is
      hampered by gastrointestinal, cardiovascular and renal side effects. Nitric oxide
      (NO)-releasing NSAIDs, NO-NSAID, are a new class of anti-inflammatory and
      analgesic drugs generated by adding a nitroxybutyl or a nitrosothiol moiety to
      the parent NSAID via a short-chain ester linkage. While efficacy of nitrosothiol
      NSAIDs still awaits investigation, nitroxybutyl-NO-NSAIDs have been extensively
      studied in humans. The combination of balanced inhibition of the two main COX
      isoforms with release of NO confers to NO-NSAIDs reduced gastrointestinal and
      cardiorenal toxicity. It is suggested that the NO, which is released as the
      compounds are broken down, may counteract the consequences of the NSAID-induced
      decrease in gastric mucosal prostaglandins. Recent clinical trials with NO-NSAIDs
      have provided data consistent with pre-clinical observations.

PMID- 16613573
TI  - Synthetic and natural coumarins as antioxidants.
AB  - Coumarins, an old class of compounds, are naturally occurring benzopyrene
      derivatives. A lot of coumarins have been identified from natural sources,
      especially green plants. These natural compounds have served as valuable leads
      for further design and synthesis of more active analogs. The pharmacological and
      biochemical properties and therapeutic applications of simple coumarins depend
      upon the pattern of substitution. Coumarins have attracted intense interest in
      recent years because of their diverse pharmacological properties. Among these
      properties, their antioxidant effects were extensively examined. In this review,
      plant derived coumarins and their synthetic analogs will be systematically
      evaluated based on their plant origin, structure-activity relationship and
      antioxidant efficacy. Owing their diverse effects and inconclusive results from
      different in vitro studies, the mechanism of their action has not yet been fully
      understood and the correlation of effects with chemical structure is not
      conclusive at the moment. It is the objective of this review will be to summarize
      experimental data for different coumarins used as antioxidant agents, because
      promising data have been reported for a series of these agents. In addition,
      their ability to bind metal ions represents an additional means of modulating
      their pharmacological responses.

PMID- 16613574
TI  - Structural features of new quinolones and relationship to antibacterial activity
      against Gram-positive bacteria.
AB  - A major recent focus of quinolone antibacterials has been the development of
      agents with enhanced activity against Gram-positive bacteria. The extensive
      research efforts have enabled a better definition of the structural features of
      quinolones that offer the best combination of clinical efficacy and reduced
      resistance selection in Gram-positive bacteria. This review considers the
      structural features of new quinolones and relationship to antibacterial activity
      against Gram-positive bacteria, while trying to position them in the context of
      recent and possible future advances based on an understanding of their chemical
      structure and how these impact on target specificity, avoidance of efflux and
      prevention of emergence of quinolone-resistant mutants in Gram-positive bacteria.

PMID- 16613575
TI  - Towards the targeted therapy of melanoma.
AB  - Novel anti-cancer treatments use knowledge about the underlying biology of the
      tumor to find suitable molecular targets. The recent years have seen great
      advances in understanding the biology of melanoma. In the current review we
      discuss the most promising molecular targets for melanoma and suggest possible
      strategies for overcoming resistance.

PMID- 16613576
TI  - Ifosfamide. Metabolic studies, new therapeutic approaches and new analogs.
AB  - Ifosfamide (IFO), an oxazaphosphorine-type anticancer alkylating agent, was found
      to be particularly useful in the treatment of a wide variety of neoplasm in
      adults and children. IFO is a positional isomer of cyclophosphamide (CPA) and was
      introduced into clinical practice in the 80s and has recently attracted much
      attention. Therapeutic application of high-dose IFO is limited by several side
      effects; among them neurotoxicity and nephrotoxicity give the greatest concern.
      The presence of these side-effects is likely to be connected with the metabolism
      of this drug. In recent years there have been many studies aiming better
      understanding metabolism of this drug, employing new therapeutic approaches and
      preparing new analogs.

PMID- 16613578
TI  - Calcium signalling and reactive oxygen species in non-excitable cells.
AB  - Reactive oxygen species can induce several biological processes by stimulating
      signal transduction components such as cytosolic free calcium concentration. The
      physiological significance of the role of biological oxidants in the regulation
      of calcium signalling pathway as well as the mechanisms of the oxidant
      stimulation of signal transduction are discussed in this review.

PMID- 16613577
TI  - The role of genistein and synthetic derivatives of isoflavone in cancer
      prevention and therapy.
AB  - Genistein, one of the predominant soy isoflavones, has been shown to compete with
      17beta-estradiol for estrogen receptor binding because of its structural
      similarity, resulting in agonistic or antagonistic activity. It causes inhibition
      of cell growth in breast and prostate cancers in vivo and in vitro. From gene
      expression profiles, genistein has been found to regulate the genes that are
      critical for the control of cell proliferation, cell cycle, apoptosis,
      oncogenesis, transcription regulation, and cell signal transduction pathways. It
      has been reported that genistein induces apoptosis and inhibits activation of NF
      kappaB and Akt signaling pathways, both of which are known to maintain a balance
      between cell survival and apoptosis. Recently, we found that genistein sensitized
      cancer cells to apoptosis induced by chemotherapeutic agents including docetaxel,
      gemcitabine and cisplatin through inactivation of NF-kappaB in multiple cancer
      cell lines. To enhance the anti-cancer activity of genistein, we have synthesized
      structurally-modified derivatives of isoflavone based on the structural
      requirements for optimal anti-cancer effect. We found that these synthetic
      derivatives of isoflavone exerted higher anti-cancer activity with lower IC50.
      These derivatives of isoflavone also induced more apoptosis compared to
      genistein. These results suggest that genistein and synthetic structurally
      modified derivatives of isoflavone may be promising agents for cancer
      chemoprevention and therapy either alone or in combination with existing
      chemotherapeutic agents.

PMID- 16613579
TI  - Review in pharmacokinetic models on corticosteroids.
AB  - The pharmacokinetics of corticosteroids provides a large set of mathematical
      models which led to analyse many kinetic profiles corresponding to many clinical
      and/or physiological situations. In this paper, we present a review on the
      usefulness, advantages and limits of such models which could find a large
      application in medicinal chemistry.

PMID- 16613580
TI  - Recent advances in anti-influenza agents with neuraminidase as target.
AB  - Neuraminidase (NA) is the major surface glycoprotein of the influenza virus. It
      has been considered a suitable target for designing agents against influenza
      viruses. Rational drug design of NA inhibitors is now in the clinic and is
      effective for the treatment of influenza. Recently, research of structure-based
      NA inhibitors is becoming an interesting field, leading to a breakthrough in the
      control of influenza. Here we review a series of neuraminidase inhibitors and the
      recent progress in this field.

PMID- 16613581
TI  - Prediction of compounds with specific pharmacodynamic, pharmacokinetic or
      toxicological property by statistical learning methods.
AB  - Computational methods for predicting compounds of specific pharmacodynamic,
      pharmacokinetic, or toxicological property are useful for facilitating drug
      discovery and drug safety evaluation. The quantitative structure-activity
      relationship (QSAR) and quantitative structure-property relationship (QSPR)
      methods are the most successfully used statistical learning methods for
      predicting compounds of specific property. More recently, other statistical
      learning methods such as neural networks and support vector machines have been
      explored for predicting compounds of higher structural diversity than those
      covered by QSAR and QSPR. These methods have shown promising potential in a
      number of studies. This article is intended to review the strategies, current
      progresses and underlying difficulties in using statistical learning methods for
      predicting compounds of specific property. It also evaluates algorithms commonly
      used for representing structural and physicochemical properties of compounds.

PMID- 16613582
TI  - Geminin as a molecular target for the development of new anticancer drugs.
AB  - The unique biological properties of Geminin, particularly as an inhibitor of DNA
      replication initiation, have been recognized, and this has prompted a number of
      investigations into this molecule to explore its potential therapeutic as well as
      diagnostic usefulness. This review summarizes the possibility of Geminin serving
      as a new molecular target in the development of new anticancer drugs.

PMID- 16613583
TI  - Functional chemokine receptors in allergic diseases: is CCR8 a novel therapeutic
      target?
AB  - CC chemokine receptor (CCR) 8, which is expressed on Th2 cells and eosinophils,
      has been implicated in allergic diseases. This review represents an overview of
      the functional roles of CCR8 in the pathogenesis of eosinophilic inflammation and
      debates the potential of recently developed CCR8 antagonists to treat allergic
      disorders.

PMID- 16613584
TI  - A classical QSAR study on some platelet aggregation inhibitors.
AB  - Cardiovascular diseases are still the main cause of morbidity and mortality in
      the world. Anti-platelet drugs have found clinical application in the secondary
      prevention of vascular events including acute myocardial infarction, stroke and
      cardiovascular death. In the present review, we have developed sixteen
      quantitative structure-activity relationships (QSAR) for different sets of
      compounds that are X-phenols (I), X-catechols (II), caffeic acid amides (III), X
      alcohols (IV), 1,4-naphthoquinones (V), tetrahydronaphthalenes (VI),
      phenoxyacetaldehyde guanylhydrazones (VII), pyrrolobenzylisoquinolines (VIII) and
      phosphonic acids (IX) with respect to their anti-platelet activities. QSAR
      results have shown that the anti-platelet activities of these compounds are
      largely dependent not only on their hydrophobicity, but also on the influence of
      their molar refractivity.

PMID- 16613585
TI  - Allosteric modulation of drug binding to human serum albumin.
AB  - Human serum albumin (HSA), the most prominent protein in plasma, is best known
      for its extraordinary ligand binding capacity. The three homologous domains of
      HSA (labeled I, II, and III), each in turn composed of two subdomains (named A
      and B), give rise to the three-dimensional structure of HSA. This flexible
      structural organization allows the protein structure to adapt to a variety of
      ligands. As conformational adaptability of HSA extends well beyond the immediate
      vicinity of the binding site(s), cooperativity and allosteric modulation arise
      among binding sites; this makes HSA similar to a multimeric protein. Although
      kinetic and thermodynamic parameters for ligand binding to HSA calculated by
      quantitative structure-activity relationship models are in excellent agreement
      with those obtained in vitro, cooperative and allosteric equilibria between
      different binding sites and competition between drugs or between drugs and
      endogenous ligands make difficult the interpretation of HSA binding properties in
      vivo. Binding of exogenous and endogenous ligands to HSA appears to be relevant
      in drug therapy and management. Here, the allosteric modulation of drug binding
      to HSA is briefly reviewed.

PMID- 16613586
TI  - Glycaemic instability is an underestimated problem in Type II diabetes.
AB  - The aim of the present study was to assess the level of glycaemic control by the
      measurement of 24 h blood glucose profiles and standard blood analyses under
      identical nutritional and physical activity conditions in patients with Type II
      diabetes and healthy normoglycaemic controls. A total of 11 male patients with
      Type II diabetes and 11 healthy matched controls participated in a 24 h CGMS
      (continuous subcutaneous glucose-monitoring system) assessment trial under
      strictly standardized dietary and physical activity conditions. In addition,
      fasting plasma glucose, insulin and HbA(1c) (glycated haemoglobin) concentrations
      were measured, and an OGTT (oral glucose tolerance test) was performed to
      calculate indices of whole-body insulin sensitivity, oral glucose tolerance
      and/or glycaemic control. In the healthy control group, hyperglycaemia (blood
      glucose concentration >10 mmol/l) was hardly present (2+/-1% or 0.4+/-0.2/24 h).
      However, in the patients with Type II diabetes, hyperglycaemia was experienced
      for as much as 55+/-7% of the time (13+/-2 h over 24 h) while using the same
      standardized diet. Breakfast-related hyperglycaemia contributed most (46+/-7%;
      P<0.01 as determined by ANOVA) to the total amount of hyperglycaemia and
      postprandial glycaemic instability. In the diabetes patients, blood HbA(1c)
      content correlated well with the duration of hyperglycaemia and the postprandial
      glucose responses (P<0.05). In conclusion, CGMS determinations show that standard
      measurements of glycaemic control underestimate the amount of hyperglycaemia
      prevalent during real-life conditions in Type II diabetes. Given the macro- and
      micro-vascular damage caused by postprandial hyperglycaemia, CGMS provides an
      excellent tool to evaluate alternative therapeutic strategies to reduce
      hyperglycaemic blood glucose excursions.

PMID- 16613589
TI  - Recent trends and results for organ donation and transplantation in the United
      States, 2005.

PMID- 16613587
TI  - Identification of a nuclear-localized nuclease from wheat cells undergoing
      programmed cell death that is able to trigger DNA fragmentation and apoptotic
      morphology on nuclei from human cells.
AB  - PCD (programmed cell death) in plants presents important morphological and
      biochemical differences compared with apoptosis in animal cells. This raises the
      question of whether PCD arose independently or from a common ancestor in plants
      and animals. In the present study we describe a cell-free system, using wheat
      grain nucellar cells undergoing PCD, to analyse nucleus dismantling, the final
      stage of PCD. We have identified a Ca2+/Mg2+ nuclease and a serine protease
      localized to the nucleus of dying nucellar cells. Nuclear extracts from nucellar
      cells undergoing PCD triggered DNA fragmentation and other apoptotic morphology
      in nuclei from different plant tissues. Inhibition of the serine protease did not
      affect DNA laddering. Furthermore, we show that the nuclear extracts from plant
      cells triggered DNA fragmentation and apoptotic morphology in nuclei from human
      cells. The inhibition of the nucleolytic activity with Zn2+ or EDTA blocked the
      morphological changes of the nucleus. Moreover, nuclear extracts from apoptotic
      human cells triggered DNA fragmentation and apoptotic morphology in nuclei from
      plant cells. These results show that degradation of the nucleus is
      morphologically and biochemically similar in plant and animal cells. The
      implication of this finding on the origin of PCD in plants and animals is
      discussed.

PMID- 16613590
TI  - Organ donation and utilization, 1995-2004: entering the collaborative era.
AB  - Continued progress in organ donation will help enable transplantation to
      alleviate the increasing incidence of end-stage organ disease. This article
      discusses the implementation and effect of the federally initiated Organ Donation
      Breakthrough Collaborative; it then reviews organ donation data, living and
      deceased, from 1995 to 2004. It is the first annual report of the Scientific
      Registry of Transplant Recipients to include national data following initiation
      of the collaborative in 2003. Prior to that, annual growth in deceased donation
      was 2%-4%; in 2004, after initiation of the collaborative, deceased donation
      increased 11%. Identification and dissemination of best practices for organ
      donation have emphasized new strategies for improved consent, including revised
      approaches to minority participation, timing of requests and team design. The
      number of organs recovered from donation after cardiac death (DCD) grew from 64
      in 1995 to 391 in 2004. While efforts are ongoing to develop methodologies for
      identifying expanded criteria donors (ECD) for organs other than kidney, it is
      clear DCD and ECD raise questions regarding cost and recovery. The number of
      living donor organs increased from 3493 in 1995 to 7002 in 2004; data show trends
      toward more living unrelated donors and those providing non-directed donations.

PMID- 16613591
TI  - Immunosuppression: evolution in practice and trends, 1994-2004.
AB  - Over the last 10 years, there have been important changes in immunosuppression
      management and strategies for solid-organ transplantation, characterized by the
      use of new immunosuppressive agents and regimens. An organ-by-organ review of
      OPTN/SRTR data showed several important trends in immunosuppression practice.
      There is an increasing trend toward the use of induction therapy with antibodies,
      which was used for most kidney, pancreas after kidney (PAK), simultaneous
      pancreas-kidney (SPK) and pancreas transplant alone (PTA) recipients in 2004 (72
      81%) and for approximately half of all intestine, heart and lung recipients. The
      highest usage of the tacrolimus/mycophenolate mofetil combination as discharge
      regimen was reported for SPK (72%) and PAK (64%) recipients. Maintenance of the
      original discharge regimen through the first 3 years following transplantation
      varied significantly by organ and drug. The usage of calcineurin inhibitors for
      maintenance therapy was characterized by a clear transition from cyclosporine to
      tacrolimus. Corticosteroids were administered to the majority of patients;
      however, steroid-avoidance and steroid-withdrawal protocols have become
      increasingly common. The percentage of patients treated for acute rejection
      during the first year following transplantation has continued to decline,
      reaching 13% for those who received a kidney in 2003, 48% of which cases were
      treated with antibodies.

PMID- 16613592
TI  - Pediatric transplantation in the United States, 1995-2004.
AB  - This article reviews trends in pediatric solid organ transplantation over the
      last decade, as reflected in OPTN/SRTR data. In 2004, children younger than 18
      years made up nearly 3% of the 86,378 candidates for organ transplantation and
      nearly 7% of the 27,031 organ transplant recipients. Children accounted for
      nearly 14% of the 7152 deceased organ donors. The transplant community recognizes
      important differences between pediatric and adult organ transplant recipients,
      including different etiologies of organ failure, surgical procedures that are
      more complex or technically challenging, effects of development on the
      pharmacokinetic properties of common immunosuppressants, unique immunological
      aspects of transplant in the developing immune system and increased
      susceptibility to posttransplant complications, particularly infectious diseases.
      For these reasons, and because of the impact of end-stage organ failure on growth
      and development, the transplant community has generally provided pediatric
      candidates with special consideration in the allocation of deceased donor organs.
      Outcomes following kidney, liver and heart transplantation in children often rank
      among the best. This article emphasizes that the prospects for solid organ
      transplantation in children, especially those aged 1-10 years are excellent. It
      also identifies themes warranting further consideration, including organ
      availability, adolescent survival and challenges facing pediatric transplant
      clinical research.

PMID- 16613593
TI  - Kidney and pancreas transplantation in the United States, 1995-2004.
AB  - This article examines OPTN/SRTR data on kidney and pancreas transplantation for
      2004 and the previous decade, and discusses recent changes in kidney-pancreas
      (KP) allocation policy and emerging issues in kidney donation after cardiac death
      (DCD). Although the number of kidney donors continues to increase, new waiting
      list registrations again outpaced the number of kidney transplants performed,
      rising by 11% between 2003 and 2004 and contributing to a 1-year increase of 8%
      in the number of patients active on the waiting list. DCD has increased steadily
      since 2000; 39% more DCD transplants were performed in 2004 than 2003. Both
      deceased donor and living donor kidney graft survival rates remain excellent and
      are improving. The number of people living with a functioning kidney transplant
      doubled between 1995 and 2004, to 101,440 with a functioning kidney-alone and
      7213 with a functioning KP. Health care providers in all settings are more likely
      to be exposed to these transplant recipients. Patient survival following
      simultaneous pancreas-kidney (SPK) transplantation is excellent and has improved
      incrementally since 1995; death rates in the first year fell from 60 per 1000
      patient-years at risk in 2001 to 45 in 2003. The number of solitary pancreas
      transplants increased dramatically in 2004.

PMID- 16613594
TI  - Liver and intestine transplantation in the United States, 1995-2004.
AB  - Three years of survival data are now available and the impact of the model for
      end-stage liver disease (MELD) allocation system is becoming clear. After a
      decline in new registrants to the waiting list in 2002, the number increased to
      10 856 new patients in 2004. Since the implementation of MELD, the percentage of
      patients who have been on the list for 1-2 years has declined from 24% to 19%.
      There has been a shift upward in the percentage of patients with higher MELD
      scores on the waiting list. An increasing percentage of adult living donor liver
      recipients are over the age of 50 years; from 1% in 1997 to 51% in 2004. Parents
      donating to children (93% of living donors in 1995), represented only 14% in
      2004. Long-term adjusted patient survival declined with increasing recipient age
      in adults following either DDLT or LDLT. Cirrhosis caused by chronic hepatitis C
      virus (HCV) is the leading indication for liver transplantation and is associated
      with reduced long-term survival in recipients with HCV compared to those without
      HCV, 68% at 5 years compared to 76%. Although the intestine waiting list has more
      than doubled over the last decade, an increasing number of centers now perform
      intestinal transplantation with greater success.

PMID- 16613595
TI  - Thoracic organ transplantation in the United States, 1995-2004.
AB  - This article reviews trends in thoracic organ transplantation based on OPTN/SRTR
      data from 1995 to 2004. The number of active waiting list patients for heart
      transplants continues to decline, primarily because there are fewer patients with
      coronary artery disease listed for transplantation. Waiting times for heart
      transplantation have decreased, and waiting list deaths also have declined, from
      259 per 1000 patient-years at risk in 1995 to 156 in 2004. Fewer heart
      transplants were performed in 2004 than in 1995, but adjusted patient survival
      increased to 88% at 1 year and 73% at 5 years. Emphysema, idiopathic pulmonary
      fibrosis and cystic fibrosis were the most common indications among lung
      transplant recipients in 2004. Waiting time for lung transplantation decreased
      between 1999 and 2004. Waiting list mortality decreased to 134 per 1000 patient
      years at risk in 2004. One-year survival following transplantation has improved
      significantly in the past decade. The number of combined heart-lung transplants
      performed in the United States remains low, with only 39 performed in 2004.
      Overall unadjusted survival, at 58% at 1 year and 40% at 5 years, is lower among
      heart-lung recipients than among either heart or lung recipients alone.

PMID- 16613596
TI  - SRTR center-specific reporting tools: Posttransplant outcomes.
AB  - Measuring and monitoring performance--be it waiting list and posttransplant
      outcomes by a transplant center, or organ donation success by an organ
      procurement organization and its partnering hospitals--is an important component
      of ensuring good care for people with end-stage organ failure. Many parties have
      an interest in examining these outcomes, from patients and their families to
      payers such as insurance companies or the Centers for Medicare and Medicaid
      Services; from primary caregivers providing patient counseling to government
      agencies charged with protecting patients. The Scientific Registry of Transplant
      Recipients produces regular, public reports on the performance of transplant
      centers and organ procurement organizations. This article explains the
      statistical tools used to prepare these reports, with a focus on graft survival
      and patient survival rates of transplant centers--especially the methods used to
      fairly and usefully compare outcomes of centers that serve different populations.
      The article concludes with a practical application of these statistics--their use
      in screening transplant center performance to identify centers that may need
      remedial action by the OPTN/UNOS Membership and Professional Standards Committee.

PMID- 16613597
TI  - Development of the new lung allocation system in the United States.
AB  - This article reviews the development of the new U.S. lung allocation system that
      took effect in spring 2005. In 1998, the Health Resources and Services
      Administration of the U.S. Department of Health and Human Services published the
      Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule,
      which became effective in 2000, the OPTN had to demonstrate that existing
      allocation policies met certain conditions or change the policies to meet a range
      of criteria, including broader geographic sharing of organs, reducing the use of
      waiting time as an allocation criterion and creating equitable organ allocation
      systems using objective medical criteria and medical urgency to allocate donor
      organs for transplant. This mandate resulted in reviews of all organ allocation
      policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN
      Thoracic Organ Transplantation Committee. This paper reviews the deliberations of
      the Subcommittee in identifying priorities for a new lung allocation system, the
      analyses undertaken by the OPTN and the Scientific Registry for Transplant
      Recipients and the evolution of a new lung allocation system that ranks
      candidates for lungs based on a Lung Allocation Score, incorporating waiting list
      and posttransplant survival probabilities.

PMID- 16613598
TI  - Analytical methods and database design: implications for transplant researchers,
      2005.
AB  - Understanding how transplant data are collected is crucial to understanding how
      the data can be used. The collection and use of Organ Procurement and
      Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR)
      data continues to evolve, leading to improvements in data quality, timeliness and
      scope while reducing the data collection burden. Additional ascertainment of
      outcomes completes and validates existing data, although caveats remain for
      researchers. We also consider analytical issues related to cohort choice, timing
      of data submission, and transplant center variations in follow-up data. All of
      these points should be carefully considered when choosing cohorts and data
      sources for analysis. The second part of the article describes some of the
      statistical methods for outcome analysis employed by the SRTR. Issues of cohort
      and follow-up period selection lead into a discussion of outcome definitions,
      event ascertainment, censoring and covariate adjustment. We describe methods for
      computing unadjusted mortality rates and survival probabilities, and estimating
      covariate effects through regression modeling. The article concludes with a
      description of simulated allocation modeling, developed by the SRTR for comparing
      outcomes of proposed changes to national organ allocation policies.

PMID- 16613599
TI  - Solitary pulmonary metastasis from primary melanoma of the oesophagus 5 years
      after resection of the primary tumor.
AB  - BACKGROUND: Primary malignant melanoma of the oesophagus (PMME) is an uncommon
      tumor. PMME has an aggressive biological behavior, similar to melanomas developed
      elsewhere in the body. Most patients die from distant metastases, and the overall
      5 year survival rate is approximately 4%. CASE PRESENTATION: We report a rare
      case of a solitary pulmonary metastasis found 5 years after curative resection of
      primary esophageal melanoma. No other sites of metastatic disease were
      identified. Video-assisted lung wedge resection of the lung nodule was carried
      out successfully. CONCLUSION: This supports the concept that patients with
      primary melanoma of the oesophagus treated should be carefully followed up.

PMID- 16613600
TI  - Nucleus accumbens corticotropin-releasing factor increases cue-triggered
      motivation for sucrose reward: paradoxical positive incentive effects in stress?
AB  - BACKGROUND: Corticotropin-releasing factor (CRF) is typically considered to
      mediate aversive aspects of stress, fear and anxiety. However, CRF release in the
      brain is also elicited by natural rewards and incentive cues, raising the
      possibility that some CRF systems in the brain mediate an independent function of
      positive incentive motivation, such as amplifying incentive salience. Here we
      asked whether activation of a limbic CRF subsystem magnifies the increase in
      positive motivation for reward elicited by incentive cues previously associated
      with that reward, in a way that might exacerbate cue-triggered binge pursuit of
      food or other incentives? We assessed the impact of CRF microinjections into the
      medial shell of nucleus accumbens using a pure incentive version of Pavlovian
      Instrumental transfer, a measure specifically sensitive to the incentive salience
      of reward cues (which it separates from influences of aversive stress, stress
      reduction, frustration and other traditional explanations for stress-increased
      behavior). Rats were first trained to press one of two levers to obtain sucrose
      pellets, and then separately conditioned to associate a Pavlovian cue with free
      sucrose pellets. On test days, rats received microinjections of vehicle, CRF (250
      or 500 ng/0.2 microl) or amphetamine (20 microg/0.2 microl). Lever pressing was
      assessed in the presence or absence of the Pavlovian cues during a half-hour
      test. RESULTS: Microinjections of the highest dose of CRF (500 ng) or amphetamine
      (20 microg) selectively enhanced the ability of Pavlovian reward cues to trigger
      phasic peaks of increased instrumental performance for a sucrose reward, each
      peak lasting a minute or so before decaying after the cue. Lever pressing was not
      enhanced by CRF microinjections in the baseline absence of the Pavlovian cue or
      during the presentation without a cue, showing that the CRF enhancement could not
      be explained as a result of generalized motor arousal, frustration or stress, or
      by persistent attempts to ameliorate aversive states. CONCLUSION: We conclude
      that CRF in nucleus accumbens shell amplifies positive motivation for cued
      rewards, in particular by magnifying incentive salience that is attributed to
      Pavlovian cues previously associated with those rewards. CRF-induced
      magnification of incentive salience provides a novel explanation as to why stress
      may produce cue-triggered bursts of binge eating, drug addiction relapse, or
      other excessive pursuits of rewards.

PMID- 16613601
TI  - Comparison of perceived and modelled geographical access to accident and
      emergency departments: a cross-sectional analysis from the Caerphilly Health and
      Social Needs Study.
AB  - BACKGROUND: Assessment of the spatial accessibility of hospital accident and
      emergency departments as perceived by local residents has not previously been
      investigated. Perceived accessibility may affect where, when, and whether
      potential patients attend for treatment. Using data on 11,853 respondents to a
      population survey in Caerphilly county borough, Wales, UK, we present an analysis
      comparing the accessibility of accident and emergency departments as reported by
      local residents and drive-time to the nearest accident and emergency department
      modelled using a geographical information system (GIS). RESULTS: Median drive
      times were significantly shorter in the lowest perceived access category and
      longer in the best perceived access category (p < 0.001). The perceived access
      and GIS modelled drive-time variables were positively correlated (Spearman's rank
      correlation coefficient, r = 0.38, p < 0.01). The strongest correlation was found
      for respondents living in areas in which nearly all households had a car or van
      (r = 0.47, p < 0.01). Correlations were stronger among respondents reporting good
      access to public transport and among those reporting a recent accident and
      emergency attendance for injury treatment compared to other respondents.
      Correlation coefficients did not vary substantially by levels of household
      income. Drive-time, road distance and straight-line distance were highly inter
      correlated and substituting road distance or straight-line distance as the GIS
      modelled spatial accessibility measure only marginally decreased the magnitude of
      the correlations between perceived and GIS modelled access. CONCLUSION: This
      study provides evidence that the accessibility of hospital-based health care
      services as perceived by local residents is related to measures of spatial
      accessibility modelled using GIS. For studies that aim to model geographical
      separation in a way that correlates well with the perception of local residents,
      there may be minimal advantage in using sophisticated measures. Straight-line
      distance, which can be calculated without GIS, may be as good as GIS-modelled
      drive-time or distance for this purpose. These findings will be of importance to
      health policy makers and local planners who seek to obtain local information on
      access to services through focussed assessments of residents' concerns over
      accessibility and GIS modelling.

PMID- 16613602
TI  - SIMAGE: simulation of DNA-microarray gene expression data.
AB  - BACKGROUND: Simulation of DNA-microarray data serves at least three purposes: (i)
      optimizing the design of an intended DNA microarray experiment, (ii) comparing
      existing pre-processing and processing methods for best analysis of a given DNA
      microarray experiment, (iii) educating students, lab-workers and other
      researchers by making them aware of the many factors influencing DNA microarray
      experiments. RESULTS: Our model has multiple layers of factors influencing the
      experiment. The relative influence of such factors can differ significantly
      between labs, experiments within labs, etc. Therefore, we have added a module to
      roughly estimate their parameters from a given data set. This guarantees that our
      simulated data mimics real data as closely as possible. CONCLUSION: We introduce
      a model for the simulation of dual-dye cDNA-microarray data closely resembling
      real data and coin the model and its software implementation "SIMAGE" which
      stands for simulation of microarray gene expression data. The software is freely
      accessible at: http://bioinformatics.biol.rug.nl/websoftware/simage.

PMID- 16613604
TI  - ROC and confusion analysis of structure comparison methods identify the main
      causes of divergence from manual protein classification.
AB  - BACKGROUND: Current classification of protein folds are based, ultimately, on
      visual inspection of similarities. Previous attempts to use computerized
      structure comparison methods show only partial agreement with curated databases,
      but have failed to provide detailed statistical and structural analysis of the
      causes of these divergences. RESULTS: We construct a map of
      similarities/dissimilarities among manually defined protein folds, using a score
      cutoff value determined by means of the Receiver Operating Characteristics curve.
      It identifies folds which appear to overlap or to be "confused" with each other
      by two distinct similarity measures. It also identifies folds which appear
      inhomogeneous in that they contain apparently dissimilar domains, as measured by
      both similarity measures. At a low (1%) false positive rate, 25 to 38% of domain
      pairs in the same SCOP folds do not appear similar. Our results suggest either
      that some of these folds are defined using criteria other than purely structural
      consideration or that the similarity measures used do not recognize some relevant
      aspects of structural similarity in certain cases. Specifically, variations of
      the "common core" of some folds are severe enough to defeat attempts to
      automatically detect structural similarity and/or to lead to false detection of
      similarity between domains in distinct folds. Structures in some folds vary
      greatly in size because they contain varying numbers of a repeating unit, while
      similarity scores are quite sensitive to size differences. Structures in
      different folds may contain similar substructures, which produce false positives.
      Finally, the common core within a structure may be too small relative to the
      entire structure, to be recognized as the basis of similarity to another.
      CONCLUSION: A detailed analysis of the entire available protein fold space by two
      automated similarity methods reveals the extent and the nature of the divergence
      between the automatically determined similarity/dissimilarity and the manual fold
      type classifications. Some of the observed divergences can probably be addressed
      with better structure comparison methods and better automatic, intelligent
      classification procedures. Others may be intrinsic to the problem, suggesting a
      continuous rather than discrete protein fold space.

PMID- 16613603
TI  - Upregulation of a tonoplast-localized cytochrome P450 during petal senescence in
      Petunia inflata.
AB  - BACKGROUND: Gene expression in Petunia inflata petals undergoes major changes
      following compatible pollination. Severe flower wilting occurs reproducibly
      within 36 hours, providing an excellent model for investigation of petal
      senescence and programmed cell death. Expression of a number of genes and various
      enzyme activities involved in the degradation and remobilization of
      macromolecules have been found to be upregulated during the early stages of petal
      senescence. RESULTS: By performing differential display of cDNAs during Petunia
      inflata petal senescence, a highly upregulated gene encoding a cytochrome P450
      was identified. Analysis of the complete cDNA sequence revealed that the
      predicted protein is a member of the CYP74C family (CYP74C9) and is highly
      similar to a tomato CYP74C allene oxide synthase (AOS) that is known to be active
      on 9-hydroperoxides. Cloning of the petunia genomic DNA revealed an intronless
      gene with a promoter region that carries signals found in stress-responsive genes
      and potential binding sites for Myb transcription factors. Transcripts were
      present at detectable levels in root and stem, but were 40 times more abundant in
      flowers 36 hours after pollination. Ethylene and jasmonate treatment resulted in
      transitory increases in expression in detached flowers. A protein fusion of the
      CYP74C coding region to a C-terminal GFP was found to be located in the
      tonoplast. CONCLUSION: Though oxylipins, particularly jasmonates, are known to be
      involved in stress responses, the role of other products of CYP74 enzymes is less
      well understood. The identification of a CYP74C family member as a highly
      upregulated gene during petal senescence suggests that additional products of
      fatty acid metabolism may play important roles during programmed cell death. In
      contrast to the chloroplast localization of AOS proteins in the CYP74A subfamily,
      GFP fusion data indicates that the petunia CYP74C9 enzyme is in the tonoplast.
      This result suggests that the highly similar CYP74C enzymes that have been
      identified in two other Solanaceous plants may also be associated with the
      vacuole, an organelle known to have a prominent role in programmed cell death.

PMID- 16613606
TI  - Practice area and work demands in nurses' aides: a cross-sectional study.
AB  - BACKGROUND: Knowledge of how work demands vary between different practice areas
      could give us a better understanding of the factors that influence the working
      conditions in the health services, and could help identify specific work-related
      challenges and problems in the different practice areas. In turn, this may help
      politicians, and healthcare administrators and managers to develop healthy work
      units. The aim of this study was to find out how nurses' aides' perception of
      demands and control at work vary with the practice area in which the aides are
      working. METHODS: In 1999, 12,000 nurses' aides were drawn randomly from the
      member list of the Norwegian Union of Health--and Social Workers, and were mailed
      a questionnaire. 7478 (62.3 %) filled in the questionnaire. The sample of the
      present study comprised the 6485 nurses' aides who were not on leave. Respondents
      working in one practice area were compared with respondents not working in this
      area (all together). Because of multiple comparisons, 0.01 was chosen as
      statistical significance level. RESULTS: Total quantitative work demands were
      highest in somatic hospital departments, nursing homes, and community nurse
      units. Physical demands were highest in somatic hospital departments and nursing
      homes. Level of positive challenges was highest in hospital departments and
      community nurses units, and lowest in nursing homes and homes or apartment units
      for the aged. Exposure to role conflicts was most frequent in nursing homes,
      homes or apartment units for the aged, and community nurse units. Exposure to
      threats and violence was most frequent in psychiatric departments, nursing homes,
      and institutions for mentally handicapped. Control of work pace was highest in
      psychiatric departments and institutions for mentally handicapped, and was lowest
      in somatic hospital departments and nursing homes. Participation in decisions at
      work was highest in psychiatric departments and community nurse units, and was
      lowest in somatic hospital departments and nursing homes. CONCLUSION: The demands
      and control experienced by Norwegian nurses' aides at work vary strongly with the
      practice area. Preventive workplace interventions should be tailored each area.

PMID- 16613605
TI  - Multivariable risk prediction can greatly enhance the statistical power of
      clinical trial subgroup analysis.
AB  - BACKGROUND: When subgroup analyses of a positive clinical trial are unrevealing,
      such findings are commonly used to argue that the treatment's benefits apply to
      the entire study population; however, such analyses are often limited by poor
      statistical power. Multivariable risk-stratified analysis has been proposed as an
      important advance in investigating heterogeneity in treatment benefits, yet no
      one has conducted a systematic statistical examination of circumstances
      influencing the relative merits of this approach vs. conventional subgroup
      analysis. METHODS: Using simulated clinical trials in which the probability of
      outcomes in individual patients was stochastically determined by the presence of
      risk factors and the effects of treatment, we examined the relative merits of a
      conventional vs. a "risk-stratified" subgroup analysis under a variety of
      circumstances in which there is a small amount of uniformly distributed treatment
      related harm. The statistical power to detect treatment-effect heterogeneity was
      calculated for risk-stratified and conventional subgroup analysis while varying:
      1) the number, prevalence and odds ratios of individual risk factors for risk in
      the absence of treatment, 2) the predictiveness of the multivariable risk model
      (including the accuracy of its weights), 3) the degree of treatment-related harm,
      and 5) the average untreated risk of the study population. RESULTS: Conventional
      subgroup analysis (in which single patient attributes are evaluated "one-at-a
      time") had at best moderate statistical power (30% to 45%) to detect variation in
      a treatment's net relative risk reduction resulting from treatment-related harm,
      even under optimal circumstances (overall statistical power of the study was good
      and treatment-effect heterogeneity was evaluated across a major risk factor [OR =
      3]). In some instances a multi-variable risk-stratified approach also had low to
      moderate statistical power (especially when the multivariable risk prediction
      tool had low discrimination). However, a multivariable risk-stratified approach
      can have excellent statistical power to detect heterogeneity in net treatment
      benefit under a wide variety of circumstances, instances under which conventional
      subgroup analysis has poor statistical power. CONCLUSION: These results suggest
      that under many likely scenarios, a multivariable risk-stratified approach will
      have substantially greater statistical power than conventional subgroup analysis
      for detecting heterogeneity in treatment benefits and safety related to
      previously unidentified treatment-related harm. Subgroup analyses must always be
      well-justified and interpreted with care, and conventional subgroup analyses can
      be useful under some circumstances; however, clinical trial reporting should
      include a multivariable risk-stratified analysis when an adequate externally
      developed risk prediction tool is available.

PMID- 16613607
TI  - Comparison of knee motion on Earth and in space: an observational study.
AB  - BACKGROUND: Spaceflight has been shown to cause atrophy, reduced functional
      capacity, and increased fatigue in lower-limb skeletal muscles. The mechanisms of
      these losses are not fully understood but are thought to result, in part, from
      alteration in muscle usage. METHODS: Knee-joint angles and lower-extremity muscle
      activity were measured continually, via elecrogoniometry and surface
      electromyography respectively, from two subjects during entire working days of
      activity on Earth and onboard the International Space Station (ISS). RESULTS: On
      Earth the distribution of angular positions of the knee was typically bimodal,
      with peaks of >75 degrees of flexion and in almost full extension (<15 degrees of
      flexion). However, on the ISS, a single peak in the mid-range of the available
      range of motion was seen. The knee joint was also moved through fewer excursions
      and the excursions were smaller in amplitude, resulting in a reduced span of
      angles traversed. The velocities of the excursions in space were lower than those
      used on Earth. CONCLUSION: These results demonstrate that, in space, overall knee
      joint motion is reduced, and there is a transformation in the type of muscle
      action compared to that seen on Earth, with more isometric action at the expense
      of concentric and particularly eccentric action.

PMID- 16613608
TI  - Development and implementation of an algorithm for detection of protein complexes
      in large interaction networks.
AB  - BACKGROUND: After complete sequencing of a number of genomes the focus has now
      turned to proteomics. Advanced proteomics technologies such as two-hybrid assay,
      mass spectrometry etc. are producing huge data sets of protein-protein
      interactions which can be portrayed as networks, and one of the burning issues is
      to find protein complexes in such networks. The enormous size of protein-protein
      interaction (PPI) networks warrants development of efficient computational
      methods for extraction of significant complexes. RESULTS: This paper presents an
      algorithm for detection of protein complexes in large interaction networks. In a
      PPI network, a node represents a protein and an edge represents an interaction.
      The input to the algorithm is the associated matrix of an interaction network and
      the outputs are protein complexes. The complexes are determined by way of finding
      clusters, i. e. the densely connected regions in the network. We also show and
      analyze some protein complexes generated by the proposed algorithm from typical
      PPI networks of Escherichia coli and Saccharomyces cerevisiae. A comparison
      between a PPI and a random network is also performed in the context of the
      proposed algorithm. CONCLUSION: The proposed algorithm makes it possible to
      detect clusters of proteins in PPI networks which mostly represent molecular
      biological functional units. Therefore, protein complexes determined solely based
      on interaction data can help us to predict the functions of proteins, and they
      are also useful to understand and explain certain biological processes.

PMID- 16613609
TI  - Buoyancy studies in natural communities of square gas-vacuolate archaea in
      saltern crystallizer ponds.
AB  - BACKGROUND: Possession of gas vesicles is generally considered to be advantageous
      to halophilic archaea: the vesicles are assumed to enable the cells to float, and
      thus reach high oxygen concentrations at the surface of the brine. RESULTS: We
      studied the possible ecological advantage of gas vesicles in a dense community of
      flat square extremely halophilic archaea in the saltern crystallizer ponds of
      Eilat, Israel. We found that in this environment, the cells' content of gas
      vesicles was insufficient to provide positive buoyancy. Instead, sinking/floating
      velocities were too low to permit vertical redistribution. CONCLUSION: The
      hypothesis that the gas vesicles enable the square archaea to float to the
      surface of the brines in which they live was not supported by experimental
      evidence. Presence of the vesicles, which are mainly located close to the cell
      periphery, may provide an advantage as they may aid the cells to position
      themselves parallel to the surface, thereby increasing the efficiency of light
      harvesting by the retinal pigments in the membrane.

PMID- 16613610
TI  - Corto and DSP1 interact and bind to a maintenance element of the Scr Hox gene:
      understanding the role of Enhancers of trithorax and Polycomb.
AB  - BACKGROUND: Polycomb-group genes (PcG) encode proteins that maintain homeotic
      (Hox) gene repression throughout development. Conversely, trithorax-group (trxG)
      genes encode positive factors required for maintenance of long term Hox gene
      activation. Both kinds of factors bind chromatin regions called maintenance
      elements (ME). Our previous work has shown that corto, which codes for a
      chromodomain protein, and dsp1, which codes for an HMGB protein, belong to a
      class of genes called the Enhancers of trithorax and Polycomb (ETP) that interact
      with both PcG and trxG. Moreover, dsp1 interacts with the Hox gene Scr, the DSP1
      protein is present on a Scr ME in S2 cells but not in embryos. To understand
      better the role of ETP, we addressed genetic and molecular interactions between
      corto and dsp1. RESULTS: We show that Corto and DSP1 proteins co-localize at 91
      sites on polytene chromosomes and co-immunoprecipitate in embryos. They interact
      directly through the DSP1 HMG-boxes and the amino-part of Corto, which contains a
      chromodomain. In order to search for a common target, we performed a genetic
      interaction analysis. We observed that corto mutants suppressed dsp11 sex comb
      phenotypes and enhanced AntpScx phenotypes, suggesting that corto and dsp1 are
      simultaneously involved in the regulation of Scr. Using chromatin
      immunoprecipitation of the Scr ME, we found that Corto was present on this ME
      both in Drosophila S2 cells and in embryos, whereas DSP1 was present only in S2
      cells. CONCLUSION: Our results reveal that the proteins Corto and DSP1 are
      differently recruited to a Scr ME depending on whether the ME is active, as seen
      in S2 cells, or inactive, as in most embryonic cells. The presence of a given
      combination of ETPs on an ME would control the recruitment of either PcG or TrxG
      complexes, propagating the silenced or active state.

PMID- 16613611
TI  - Plasma DNA concentration as a predictor of mortality and sepsis in critically ill
      patients.
AB  - INTRODUCTION: Risk stratification of severely ill patients remains problematic,
      resulting in increased interest in potential circulating markers, such as
      cytokines, procalcitonin and brain natriuretic peptide. Recent reports have
      indicated the usefulness of plasma DNA as a prognostic marker in various disease
      states such as trauma, myocardial infarction and stroke. The present study
      assesses the significance of raised levels of plasma DNA on admission to the
      intensive care unit (ICU) in terms of its ability to predict disease severity or
      prognosis. METHODS: Fifty-two consecutive patients were studied in a general ICU.
      Blood samples were taken on admission and were stored for further analysis.
      Plasma DNA levels were estimated by a PCR method using primers for the human beta
      haemoglobin gene. RESULTS: Sixteen of the 52 patients investigated died within 3
      months of sampling. Nineteen of the 52 patients developed either severe sepsis or
      septic shock. Plasma DNA was higher in ICU patients than in healthy controls and
      was also higher in patients who developed sepsis (192 (65-362) ng/ml versus 74
      (46-156) ng/ml, P = 0.03) or who subsequently died either in the ICU (321 (185
      430) ng/ml versus 71 (46-113) ng/ml, P < 0.001) or in hospital (260 (151-380)
      ng/ml versus 68 (47-103) ng/ml, P < 0.001). Plasma DNA concentrations were found
      to be significantly higher in patients who died in the ICU. Multiple logistic
      regression analysis determined plasma DNA to be an independent predictor of
      mortality (odds ratio, 1.002 (95% confidence interval, 1.0-1.004), P = 0.05).
      Plasma DNA had a sensitivity of 92% and a specificity of 80% when a concentration
      higher than 127 ng/ml was taken as a predictor for death on the ICU. CONCLUSION:
      Plasma DNA may be a useful prognostic marker of mortality and sepsis in intensive
      care patients.

PMID- 16613613
TI  - Benchmarking ortholog identification methods using functional genomics data.
AB  - BACKGROUND: The transfer of functional annotations from model organism proteins
      to human proteins is one of the main applications of comparative genomics.
      Various methods are used to analyze cross-species orthologous relationships
      according to an operational definition of orthology. Often the definition of
      orthology is incorrectly interpreted as a prediction of proteins that are
      functionally equivalent across species, while in fact it only defines the
      existence of a common ancestor for a gene in different species. However, it has
      been demonstrated that orthologs often reveal significant functional similarity.
      Therefore, the quality of the orthology prediction is an important factor in the
      transfer of functional annotations (and other related information). To identify
      protein pairs with the highest possible functional similarity, it is important to
      qualify ortholog identification methods. RESULTS: To measure the similarity in
      function of proteins from different species we used functional genomics data,
      such as expression data and protein interaction data. We tested several of the
      most popular ortholog identification methods. In general, we observed a
      sensitivity/selectivity trade-off: the functional similarity scores per
      orthologous pair of sequences become higher when the number of proteins included
      in the ortholog groups decreases. CONCLUSION: By combining the sensitivity and
      the selectivity into an overall score, we show that the InParanoid program is the
      best ortholog identification method in terms of identifying functionally
      equivalent proteins.

PMID- 16613612
TI  - The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by
      macrophages via activation of nuclear factor kappa B and p38 mitogen-activated
      protein kinase in rheumatoid arthritis.
AB  - S100A8 and S100A9, two Ca2+-binding proteins of the S100 family, are secreted as
      a heterodimeric complex (S100A8/A9) from neutrophils and monocytes/macrophages.
      Serum and synovial fluid levels of S100A8, S100A9, and S100A8/A9 were all higher
      in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis
      (OA), with the S100A8/A9 heterodimer being prevalent. By two-color
      immunofluorescence labeling, S100A8/A9 antigens were found to be expressed mainly
      by infiltrating CD68+ macrophages in RA synovial tissue (ST). Isolated ST cells
      from patients with RA spontaneously released larger amounts of S100A8/A9 protein
      than did the cells from patients with OA. S100A8/A9 complexes, as well as S100A9
      homodimers, stimulated the production of proinflammatory cytokines, such as tumor
      necrosis factor alpha, by purified monocytes and in vitro-differentiated
      macrophages. S100A8/A9-mediated cytokine production was suppressed significantly
      by p38 mitogen-activated protein kinase (MAPK) inhibitors and almost completely
      by nuclear factor kappa B (NF-kappaB) inhibitors. NF-kappaB activation was
      induced in S100A8/A9-stimulated monocytes, but this activity was not inhibited by
      p38 MAPK inhibitors. These results indicate that the S100A8/A9 heterodimer,
      secreted extracellularly from activated tissue macrophages, may amplify
      proinflammatory cytokine responses through activation of NF-kappaB and p38 MAPK
      pathways in RA.

PMID- 16613614
TI  - The role played by cell-substrate interactions in the pathogenesis of osteoclast
      mediated peri-implant osteolysis.
AB  - Prosthetic wear debris-induced peri-implant osteolysis is a major cause of
      aseptic loosening after total joint replacement. In this condition, wear
      particles released from the implant components induce a granulomatous
      inflammatory reaction at the interface between implant and adjacent bone, leading
      to progressive bone resorption and loss of fixation. The present study was
      undertaken to characterize definitively the phenotype of osteoclast-like cells
      associated with regions of peri-implant focal bone resorption and to compare the
      phenotypic features of these cells with those of mononucleated and multinucleated
      cells associated with polyethylene wear particles. Peri-implant tissues were
      obtained from patients undergoing hip revision surgery for aseptic loosening
      after total joint replacement. Cells were examined for the expression of several
      markers associated with the osteoclast phenotype using immunohistochemistry,
      histochemistry, and/or in situ hybridization. CD68 protein, a marker expressed by
      multiple macrophage lineage cell types, was detected in mononucleated and
      multinucleated cells associated with polyethylene particles and the bone surface.
      Cathepsin K and tartrate-resistant acid phosphatase were expressed highly in both
      mononucleated and multinucleated cells associated with the bone surface. Levels
      of expression were much lower in cells associated with polyethylene particles.
      High levels of beta3 integrin protein were detected in cells in contact with
      bone. Multinucleated cells associated with polyethylene particles exhibited faint
      positive staining. Calcitonin receptor mRNA expression was detected solely in
      multinucleated cells present in resorption lacunae on the bone surface and was
      absent in cells associated with polyethylene particles. Our findings provide
      further evidence that cells expressing the full repertoire of osteoclast
      phenotypic markers are involved in the pathogenesis of peri-implant osteolysis
      after total joint replacement. They also demonstrate that foreign body giant
      cells, although believed to be phenotypically and functionally distinct from
      osteoclasts, express many osteoclast-associated genes and gene products. However,
      the levels and patterns of expression of these genes in the two cell types
      differ. We speculate that, in addition to the role of cytokines and growth
      factors, the substrate with which these cells interact plays a critical role in
      their differential phenotypic and functional properties.

PMID- 16613615
TI  - Small volume of hypertonic saline as the initial fluid replacement in
      experimental hypodynamic sepsis.
AB  - INTRODUCTION: We conducted the present study to examine the effects of hypertonic
      saline solution (7.5%) on cardiovascular function and splanchnic perfusion in
      experimental sepsis. METHODS: Anesthetized and mechanically ventilated mongrel
      dogs received an intravenous infusion of live Escherichia coli over 30 minutes.
      After 30 minutes, they were randomized to receive lactated Ringer's solution 32
      ml/kg (LR; n = 7) over 30 minutes or 7.5% hypertonic saline solution 4 ml/kg (HS;
      n = 8) over 5 minutes. They were observed without additional interventions for
      120 minutes. Cardiac output (CO), mean arterial pressure (MAP), portal and renal
      blood flow (PBF and RBF, respectively), gastric partial pressure of CO2 (pCO2;
      gas tonometry), blood gases and lactate levels were assessed. RESULTS: E. coli
      infusion promoted significant reductions in CO, MAP, PBF and RBF (approximately
      45%, 12%, 45% and 25%, respectively) accompanied by an increase in lactate levels
      and systemic and mesenteric oxygen extraction (sO2ER and mO2ER). Widening of
      venous-arterial (approximately 15 mmHg), portal-arterial (approximately 18 mmHg)
      and gastric mucosal-arterial (approximately 55 mmHg) pCO2 gradients were also
      observed. LR and HS infusion transiently improved systemic and regional blood
      flow. However, HS infusion was associated with a significant and sustained
      reduction of systemic (18 +/- 2.6 versus 38 +/- 5.9%) and mesenteric oxygen
      extraction (18.5 +/- 1.9 versus 36.5 +/- 5.4%), without worsening other
      perfusional markers. CONCLUSION: A large volume of LR or a small volume of HS
      promoted similar transient hemodynamic benefits in this sepsis model. However, a
      single bolus of HS did promote sustained reduction of systemic and mesenteric
      oxygen extraction, suggesting that hypertonic saline solution could be used as a
      salutary intervention during fluid resuscitation in septic patients.

PMID- 16613617
TI  - Household and community socioeconomic influences on early childhood malnutrition
      in Africa.
AB  - This paper uses multilevel modelling and Demographic and Health Survey data from
      five African countries to investigate the relative contributions of compositional
      and contextual effects of socioeconomic status and place of residence in
      perpetuating differences in the prevalence of malnutrition among children in
      Africa. It finds that community clustering of childhood malnutrition is accounted
      for by contextual effects over and above likely compositional effects, that urban
      rural differentials are mainly explained by the socioeconomic status of
      communities and households, that childhood malnutrition occurs more frequently
      among children from poorer households and/or poorer communities and that living
      in deprived communities has an independent effect in some instances. This study
      also reveals that socioeconomic inequalities in childhood malnutrition are more
      pronounced in urban centres than in rural areas.

PMID- 16613616
TI  - Polymorphisms in the vascular endothelial growth factor gene and breast cancer in
      the Cancer Prevention Study II cohort.
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF) plays a central role in
      promoting angiogenesis and is over-expressed in breast cancer. At least four
      polymorphisms in the VEGF gene have been associated with changes in VEGF
      expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter
      region; and +936C/T is located in the 3'-untranslated region. METHOD: We examined
      the association between these four VEGF polymorphisms and risk for breast cancer
      among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition
      Cohort. This cohort was established in 1992 and participants were invited to
      provide a blood sample between 1998 and 2001. Included in this analysis were 501
      postmenopausal women who provided a blood sample and were diagnosed with breast
      cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free
      postmenopausal women matched to the cases with respect to age, race/ethnicity,
      and date of blood collection (controls). RESULTS: We found no association between
      any of the polymorphisms examined and overall breast cancer risk. However,
      associations were markedly different in separate analyses of invasive cancer (n =
      380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both
      hypothesized to increase expression of VEGF, were associated with increased risk
      for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI]
      1.00-2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02-2.64 for -1154 GG versus
      AA) but they were not associated with risk for in situ cancer. The +936C allele,
      which is also hypothesized to increase VEGF expression, was not clearly
      associated with invasive breast cancer (OR 1.21, 95% CI 0.88-1.67 for +936 CC
      versus TT/CT), but it was associated with reduced risk for in situ cancer (OR
      0.59, 95% CI 0.37-0.93 for CC versus TT/CT). The -634 C/G polymorphism was not
      associated with either invasive or in situ cancer. CONCLUSION: Our findings
      provide limited support for the hypothesis that the -2578C and -1154G VEGF
      alleles are associated with increased risk for invasive but not in situ breast
      cancer in postmenopausal women.

PMID- 16613618
TI  - Migration as a determinant of marriage pattern: preliminary report on
      consanguinity among Afghans.
AB  - Two sample populations, one refugee and one resident, were studied. The
      frequencies of consanguineous marriages came out to be 49.8%and 55.4%,
      respectively, for the refugees and the residents. Caste endogamy was dominant
      both in the residents and the refugees. The mean coefficient of inbreeding was
      calculated to be 0.0303 for the refugee population and 0.0332 for the resident
      population samples. First cousin marriage was the dominant type of marriage in
      both samples; father's brother's daughter (FBD) marriage was more frequent among
      the refugees while mother's brother's daughter(MBD) marriage was more frequent
      among the residents. Education has no decreasing effect on the incidence of
      consanguineous marriages. A significant difference in the pattern of marriages in
      the refugees is observed after the Saur Revolution of 1979.

PMID- 16613619
TI  - A comparison of female- and male-headed households in Tanzania and poverty
      implications.
AB  - Female- and male-headed households were compared using data from a Demographic
      and Health Survey conducted in Tanzania in 1996. Chi-squared tests showed that
      sex of head of household was highly significantly associated with: residence,
      household size and composition, radio ownership, having enough food to eat, and
      age and marital status of head of household. An analysis by the logit regression
      model showed that female-headed households were more likely than male-headed
      households to be in rural areas, be small, have fewer men, not have radios and
      not have enough food to eat. The majority of female heads of households were
      unmarried and older than male heads of households. The implication is that female
      headed households are poorer than male-headed households.

PMID- 16613620
TI  - Perceived insufficient milk as a barrier to optimal infant feeding: examples from
      Bolivia.
AB  - In its recently adopted Global Strategy on Infant and Young Child Feeding, the
      World Health Assembly called for urgent action in addressing the barriers to
      optimal feeding practices. This paper examines mothers' concerns about milk
      insufficiency as a major contributor to suboptimal infant feeding decisions,
      using survey data from peri-urban areas of two Bolivian cities. Mothers in the
      lowland modernizing city of Santa Cruz were more likely than mothers in the
      highland traditional city of Cochabamba to express concern about insufficient
      milk, and also less likely to feed their infants according to international
      recommendations. Furthermore, perceived milk insufficiency was particularly
      common among mothers of infants younger than 6 months of age -- an age at which
      infants are particularly vulnerable to the adverse effects of breast-feeding
      cessation and complementary feeding initiation. The paper concludes with policy,
      programme and research recommendations to address the critical problem of
      perceived insufficient breast milk.

PMID- 16613621
TI  - Determinants of condom use among youth in Madagascar.
AB  - The objective of this study was to identify the key determinants of condom use
      with regular and casual partners among youth in Madagascar. Data stem from a
      reproductive health survey conducted in October-December 2000 among a
      representative sample of 2440 youth aged 15-24 living in Toamasina province.
      Following theoretical models of behaviour change, logistic regression was used to
      assess the effect of AIDS awareness,personal risk perception, condom access,
      perceived condom effectiveness,self-efficacy and social support on condom use.
      Among sexually experienced youth, only about four in ten males and two in ten
      females have ever used condoms. Fewer than 15% of youth used a condom in last
      intercourse with their regular partner. Whether youth will try condoms appears to
      depend largely on the perceived effectiveness of condoms for family planning,
      access to a nearby condom source, parental support for condom use, and patterns
      of risky sexual behaviour. Young males' likelihood of using a condom with a
      regular partner increases significantly if they perceive condoms to be effective
      for family planning (OR=11.4; p=0.019). For females, it increases with level of
      self-efficacy (OR=2 1; p=0.042) and having discussed HIV prevention with someone
      in the last year (OR=2.8; p=0.022). Among males,condom use with casual partners
      is significantly higher among those who perceive themselves to be at high risk of
      sexually transmitted infections(OR=2.3; p=0.014), who believe condoms are
      effective for family planning(OR=2.8; p=0.048), who have good access to condoms
      (OR=2.9; p=0.002)and who perceive their parents support condom use (OR=1-7;
      p=0.048). In conclusion, very few youth in Toamasina are using condoms,
      highlighting the need to continue and expand adolescent reproductive health
      interventions. In this low HIV prevalence setting, it is important for these
      programmes to emphasize that condoms are effective for both pregnancy prevention
      and STI/HIV prevention.

PMID- 16613622
TI  - Isonymic relationships in ethno-social categories (Argentinian colonial period)
      including illegitimate reproduction.
AB  - Surnames provide a useful method to study the structure of human populations for
      which biological data are not available. The isonymic method has had multiple
      applications, but difficulties emerge when dealing with groups where extramarital
      reproduction is common and the sample size is small, and even more so when only
      paternal surnames are taken into account.Therefore, it could be of interest to
      retain female surnames, including those of unmarried mothers. This study was
      carried out using all birth records froman Argentinian population in the colonial
      period, which was characterized by the presence of different ethno-social groups
      (Spanish, Indian and 'Mestizo'or mixed Spanish-Indian) and various reproductive
      patterns regarding legitimacy. Coefficient of relationship by isonymy (Ri)
      kinship matrices between geographical populations were obtained, and the results
      derived from sets of surnames (paternal, maternal of legitimate and illegitimate
      children,and all surnames in the registers) compared. The results show similar
      surname distribution regardless of the set of surnames and group considered.
      Kinship Ri matrices using paternal surnames, maternal surnames of legitimate
      children, maternal surnames of illegitimate children, and the set of whole
      surnames showed the same relationships among populations, indicating a similar
      pattern for Spanish, Indian and Mixed ethno-social groups. Mantel test
      correlation between all pairs of matrices was significant in all different ethno
      social groups. The results suggest that in populations with high illegitimacy,
      such as that studied here, it is possible to include maternal surnames, even
      corresponding to single mothers, in order to consider total reproduction and
      therefore maximize sample size.

PMID- 16613623
TI  - A varied pattern of change of the sex differential in survival in the G7
      countries.
AB  - Over the course of the 20th century the sex differential in life expectancy at
      birth in the industrialized countries has widened considerably in favour of
      women. Starting in the early 1970s, the beginning of a reversal in the long-term
      pattern of this differential has been noted in some high-income countries. This
      study documents a sustained pattern of narrowing of this measure into the later
      part of the 1990s for six of the populations that comprise the G7 countries:
      Canada, France, Germany, Italy, England and Wales (as representative of the
      United Kingdom) and USA. For Japan, a persistence of widening sex differences in
      survival is noted. The sex differences in life expectancy are decomposed over
      roughly three decades (early 1970s to late 1990s) from the point of view of four
      major cause-of-death categories: circulatory diseases, cancers,
      accidents/violence/suicide, and 'other' (residual) causes. In the six countries
      where the sex gap has narrowed, this has resulted primarily from reduced sex
      differences in circulatory disease mortality, and secondarily from reduced
      differences in male and female death rates due to accidents, violence and suicide
      combined. In some of the countries sex differentials in cancer mortality have
      been converging lately, and this has also contributed to a narrowing of the
      difference in life expectancy. In Japan, males have been less successful in
      reducing their survival disadvantage in relation to Japanese women with regard to
      circulatory disease and cancer; and in the case of accidents/violence/suicide,
      male death rates increased during the 1990s. These trends explain the divergent
      pattern of the sex difference in life expectation in Japan as compared with the
      other G7 nations.

PMID- 16613624
TI  - Factors affecting the choice of cooking fuel, cooking place and respiratory
      health in the Accra metropolitan area, Ghana.
AB  - Indoor air pollution resulting from the combustion of solid fuels has been
      identified as a major health threat in the developing world. This study examines
      how the choice of cooking fuel, place of cooking and behavioural risk factors
      affect respiratory health infections in Accra, Ghana. About 65.3% of respondents
      use charcoal and 4.2% use unprocessed wood. A total of 241 (25.4%) respondents
      who cook had had respiratory health symptoms in the two weeks preceding the
      study. Household socioeconomic status and educational attainment of respondents
      were found to have a significant impact on respiratory health through their
      particular influence on the choice of cooking fuel. Households that use wood and
      charcoal have a high incidence of respiratory health symptoms. The poor are more
      affected by respiratory health problems due to their heavy dependence on solid
      fuels as compared with their wealthy counterparts. Households that cook in
      multiple purpose rooms are more affected by respiratory health problems than
      those that cook outdoors. There is a positive correlation between the presence of
      children in the kitchen during cooking and the incidence of respiratory health
      symptoms among children (r=0.31, p<0.0001). Poverty and lack of education and
      awareness are the major factors affecting the choice of cooking fuel, place of
      cooking and respiratory health in Accra.

PMID- 16613625
TI  - Children of homosexuals and transsexuals more apt to be homosexual.
AB  - Do the sexual inclinations of parents influence those of their children? Of 77
      adult children of homosexual parents who volunteered for three different
      investigations, at least 23 (30%) were currently homosexual: twelve (55%) of 22
      daughters and three (21%) of fourteen sons of lesbians; five (29%) of seventeen
      daughters and three (17%) of eighteen sons of gays; none of six sons with both a
      gay and a lesbian parent. At least 25 (32%) were currently heterosexual. Of the
      ten with transsexual parents, one of nine daughters was currently lesbian, one
      was currently heterosexual, and one was transsexual. The son's sexual preference
      was not reported. These findings suggest that parents' sexual inclinations
      influence their children's.

PMID- 16613628
TI  - Temperature-jump apparatus with Raman detection based on a solid-state tunable
      (1.80-2.05 microm) kHz optical parametric oscillator laser.
AB  - The operating characteristics of a pulsed (10 ns) tunable near-infrared (NIR)
      laser source are described for temperature-jump (T-jump) applications. A Q
      switched Nd:YLF laser (approximately 10 ns pulses) with a 1 kHz repetition rate
      is used to pump a potassium titanyl arsenate (KTA) crystal-based optical
      parametric oscillator (OPO), producing approximately 1 mJ NIR pulses that are
      tunable (1.80-2.05 microm) across the 1.9 microm vibrational overtone band of
      water. This T-jump source has been coupled to a deep ultraviolet (UV) probe laser
      for Raman studies of protein dynamics. T-jumps of up to 30 degrees C, as measured
      via the O-H stretching Raman band of water, are readily achieved. Application to
      cytochrome c unfolding is demonstrated.

PMID- 16613629
TI  - New method for the microscopic, nondestructive acquisition of ultraviolet
      resonance Raman spectra from plant cell walls.
AB  - Raman spectroscopy has long been used for the chemical analysis of organic
      matter, including natural products, using excitation wavelengths in the visible,
      infrared, or ultraviolet portions of the spectrum. The use of ultraviolet
      resonance Raman spectroscopy (UVRR) to study bulk samples of plant tissue has
      typically been carried out by rotating homogeneous macro-samples beneath the
      laser beam in order to minimize the amount of UV radiation impinging on any one
      spot, thereby avoiding its potentially damaging effects on the organic matter
      analyzed. This paper extends the use of UVRR to the study on a microscopic scale
      of individual plant cell walls by use of the controlled micro-displacement of a
      sample.

PMID- 16613630
TI  - Classification of chemical and biological warfare agent simulants by surface
      enhanced Raman spectroscopy and multivariate statistical techniques.
AB  - Initial results demonstrating the ability to classify surface-enhanced Raman
      (SERS) spectra of chemical and biological warfare agent simulants are presented.
      The spectra of two endospores (B. subtilis and B. atrophaeus), two chemical agent
      simulants (dimethyl methylphosphonate (DMMP) and diethyl methylphosphonate
      (DEMP)), and two toxin simulants (ovalbumin and horseradish peroxidase) were
      studied on multiple substrates fabricated from colloidal gold adsorbed onto a
      silanized quartz surface. The use of principal component analysis (PCA) and
      hierarchical clustering were used to evaluate the efficacy of identifying
      potential threat agents from their spectra collected on a single substrate. The
      use of partial least squares-discriminate analysis (PLS-DA) and soft independent
      modeling of class analogies (SIMCA) on a compilation of data from separate
      substrates, fabricated under identical conditions, demonstrates both the
      feasibility and the limitations of this technique for the identification of known
      but previously unclassified spectra.

PMID- 16613631
TI  - Correlating changes in collagen secondary structure with aging and defective type
      II collagen by Raman spectroscopy.
AB  - A novel application of Raman spectroscopy for monitoring damage to ocular
      collagen in wild-type mice and Del1 (+/-) transgenic mice, a murine animal model
      of osteoarthritis, is described. In order to understand the progression of
      diseases of collagen, it is necessary to use methods that can recognize
      alterations in affected tissue due to chemical and/or genetic modifications. The
      heterozygous Del1 (+/-) transgenic mouse is established as a model for early
      onset osteoarthritis caused by modifications to the type II collagen gene
      (COL2A1) that result in a truncated collagen fiber. We expect that abnormal type
      II collagen is expressed in articular cartilage and eye tissue of the Del1 (+/-)
      mouse. Eyes excised from a subset of specimens from another study using Del1 (+/
      ) mice were examined by Raman spectroscopy for evidence of defective collagen.
      Spectral contributions from the collagen protein were readily observed. The amide
      III envelope (1220-1280 cm-1) was used to characterize changes in collagen
      secondary structure. Raman spectra of the sclera component of eyes taken from
      transgenic and older wild-type mice show an increased collagen disorder, as
      expected. These preliminary results suggest that Raman is capable of recognizing
      and measuring abnormality in eye collagen and may have potential as a diagnostic
      tool for ocular collagen damage.

PMID- 16613632
TI  - Quantitative analysis of methyl parathion pesticides in a polydimethylsiloxane
      microfluidic channel using confocal surface-enhanced Raman spectroscopy.
AB  - A fast and ultra-sensitive trace analysis of methyl parathion pesticides in a
      polydimethylsiloxane (PDMS) microfluidic channel was investigated using confocal
      surface-enhanced Raman spectroscopy (SERS). A three-dimensional PDMS-based
      passive micromixer was fabricated for this purpose. This PDMS micromixer showed a
      high mixing efficiency because a strong chaotic advection was developed by the
      simultaneous vertical and transverse dispersion of the confluent streams. The
      confocal SERS signal was measured after methyl parathion pesticides were
      effectively adsorbed onto silver nanoparticles while flowing along the upper and
      lower alligator-teeth-shaped PDMS channel. A quantitative analysis of the methyl
      parathion pesticides was performed based on the measured peak height at 1246 cm
      1. Our method has a detection limit of 0.1 ppm. This value satisfies the
      requirement recommended by the Collaborative International Pesticides Analytical
      Council (CIPAC) for the determination of methyl parathion in pesticide
      formulations. This study demonstrates the feasibility of using confocal SERS for
      the highly sensitive detection of methyl parathion pesticides in a PDMS
      microfluidic channel.

PMID- 16613633
TI  - Vibrational circular dichroism of matrix-assisted amino acid films in the mid
      infrared region.
AB  - Vibrational circular dichroism (VCD) spectra in the mid-infrared region of amino
      acid films are reported here for the first time. Amino acid films are formed from
      aqueous solutions with alpha-cyclodextrin (CD) serving as the matrix to
      facilitate the film formation. This film method eliminates the strong interfering
      water absorption seen in the solution study and makes it easier to measure the
      VCD in the 1800-1200 cm-1 region. VCD spectra for films of six amino acids, L
      alanine, L-proline, L-methionine, Lhistidine, L-phenylalanine, and L-tryptophan,
      are obtained. For amino acids with low solubility (L-phenylalanine and L
      tryptophan), VCD could not be measured in solution, so the film method is the
      only means of obtaining the VCD spectra for such amino acids. For amino acids
      with moderate solubility (L-alanine, L-proline, L-methionine, and L-histidine),
      VCD spectra are also obtained in the solution state and compared with their
      corresponding spectra in the film state. A good correlation is found between the
      film and solution spectra for both absorption and VCD. The VCD spectra of L
      methionine, L-histidine, L-phenylalanine, and Ltryptophan are reported here in
      the mid-infrared region for the first time. The present study broadens the
      application range of the VCD technique and enhances its role in the detection and
      analysis of biologically important compounds.

PMID- 16613634
TI  - Analysis of fiber blends using horizontal attenuated total reflection Fourier
      transform infrared and discriminant analysis.
AB  - We have investigated the utility of a horizontal attenuated total reflection
      Fourier transform infrared spectrometer (HATR/FT-IR) for the analysis of fiber
      and textile blends. The identification of a blended textile can be accomplished
      by subtracting a reference spectrum of the textile's most abundant component,
      leading to a difference spectrum that infers the identity of the second
      constituent of the blended textile. Mathematical post-processing of the spectra
      employing discriminant analysis provided a useful statistical tool to confirm the
      fiber blend components.

PMID- 16613635
TI  - Water diffusion behavior in epoxy resins with various fluorine contents.
AB  - In this work, novolac resin with perfluorinated side chains was synthesized and
      cured with o-Cresol novolac epoxy resin to obtain epoxy resins with various
      fluorine contents. Attenuated total reflection Fourier transform infrared
      spectroscopy (ATR/FT-IR) was used to monitor the in situ water diffusion process
      in these systems. The diffusion coefficient of water first increased and then
      slightly decreased with increasing fluorine content, which could be attributed to
      two opposite effects induced by perfluorinated side chains: enhanced
      hydrophobicity and increased free volume. In addition, generalized two
      dimensional (2D) correlation analysis was employed to investigate both the
      sorption and the desorption process of water diffusion, and two kinds of water
      molecules, named bound and free water, were found. It was interesting to find
      that in the sorption process, the change in the population of bound water
      molecules occurs earlier than the change in the population of free water
      molecules, while in the desorption process, the sequence was reversed.

PMID- 16613636
TI  - Perturbation-correlation moving-window two-dimensional correlation spectroscopy.
AB  - A new method of analysis, perturbation-correlation moving-window two-dimensional
      (PCMW2D) correlation spectroscopy, is proposed. For a spectral data set collected
      under an external perturbation, this method provides a pair of synchronous and
      asynchronous two-dimensional correlation spectra plotted on a plane between a
      spectral variable (e.g., wavenumber) axis and a perturbation variable (e.g.,
      temperature) axis. One of the advantages of this new correlation analysis method
      is that complicated spectral variation along the perturbation direction can be
      monitored. It has been found that the synchronous and asynchronous PCMW2D
      correlation spectra are similar to the first perturbation derivative and negative
      second perturbation derivative spectra of the original data, respectively. To
      demonstrate the potential of PCMW2D correlation spectroscopy, it has been applied
      to temperature-dependent infrared (IR) spectra of a poly(vinyl alcohol) (PVA)
      film. The thermal behavior of the PVA film has been revealed by the PCMW2D
      correlation analysis. Two characteristic cross-peaks are observed in the
      synchronous PCMW2D correlation spectra generated from the temperature-dependent
      IR spectra between the crystalline phase C-O stretching band at 1141 cm-1 and the
      melting temperature of 209 degrees C and between the amorphous phase C-O
      stretching band at 1095 cm-1 and another specific temperature of 233 degrees C.
      This specific temperature of 233 degrees C corresponds to the thermal degradation
      temperature due to the elimination of the hydroxyl group attached to the main
      chain.

PMID- 16613637
TI  - Transformation of time-resolved spectra to lifetime-resolved spectra by maximum
      entropy inversion of the laplace transform.
AB  - We present a method for the analysis of time-resolved spectroscopic data
      following first-order kinetics. The time traces at all the available
      spectroscopic channels (e.g., wavelength or wavenumber) are inverse Laplace
      transformed. The transformation is stabilized by the maximum entropy method
      generalized for solutions without sign-restriction. In this way, time-resolved
      spectra can be converted to lifetime-resolved spectra, where bands appear at
      coordinates corresponding to their spectroscopic maxima and time constant of
      appearance (negative amplitude) or disappearance (positive amplitude). From the
      lifetime-resolved spectra, the number of exponentially decaying components, their
      time constants, and their decay-associated spectra are readily available.
      Moreover, since bands are spread in two dimensions extra band-resolution is
      possible. We named this method of transforming time-resolved spectra into
      lifetime-resolved spectra multi-spectroscopic channel maximum entropy inversion
      of the Laplace transform (M-MaxEnt-iLT). The basis of M-MaxEnt-iLT is presented
      in detail and its properties and limitations are thoroughly discussed. We also
      show how the combination of M-MaxEnt-iLT with spectral smoothing or deconvolution
      can improve the appearance and/or band resolution of the obtained lifetime
      resolved spectra.

PMID- 16613638
TI  - Observation of room-temperature 5D1 luminescence of an organoeuropium complex
      encapsulated in sol-gel glass.
AB  - In comparing emissions of the inorganic Eu3+ salts (chloride or nitrate) to
      organoeuropium complexes doped into optically transparent sol-gel glass, previous
      studies have indicated that changes in the local chemical environment by
      chelation or variation of the ligand or gel matrix compositions were found to
      leave the main spectral features of Eu3+ essentially unchanged; complexation just
      increases the emission intensity of europium and leads to broadening and
      splitting of the peaks. In all cases studied and irrespective of the excitation
      energy, the observable emission peaks result only from relaxations out of the 5D0
      excited state of Eu3+ to the first five levels of the 7F ground manifold. The
      present research examines the luminescence behavior of EuCl3 and Eu-TETA (TETA is
      the macro cycle, 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraaceticacid)
      doped into a sol-gel host; in addition to emissions from the 5D0, emission from
      the 5D1 excited state of Eu3+ is observed for the first time.

PMID- 16613639
TI  - Interference effect of iron on the determination of gold in geological samples
      using the vapor generation technique and preconcentration in a graphite furnace.
AB  - A vapor generation procedure for the production of volatile species of Au was
      studied using electrothermal atomic absorption spectrometry (ETAAS). The
      interference effects of iron in solution and in the gas phase in a quartz T-tube
      were studied for the first time in detail. A dual vapor generation system was
      used for a single heated quartz tube atomizer, so that it was possible to study
      interferences and classify them regarding their origins. Results show that both
      gas-phase and liquid-phase interferences are present. It was also concluded that
      since the total interference effect causes the Au signal to be lower as compared
      to only the presence of gas-phase interactions in the experiment, the net liquid
      phase interference from Fe should be suppressed. The method described in this
      study was used for the determination of gold in an ore reference material, Carlin
      Ore Mine, for the purpose of demonstrating the ability of the reported method to
      determine Au without any extraction procedure.

PMID- 16613640
TI  - Near-infrared spectroscopic determination of salinity and internal pressure of
      fluid inclusions in minerals.
AB  - A near-infrared (NIR) spectroscopic method is proposed to achieve the
      simultaneous determination of salinity and internal pressure of fluid inclusions
      in natural minerals. A combination band between the anti-symmetric stretching and
      bending vibrations of molecular water at approximately 5180 cm-1 was observed for
      standard salt solutions and natural minerals containing fluid inclusions with
      known salinities. A curve-fitting procedure was used to analyze the change in the
      band shape of the combination. Justification of the calibration was confirmed by
      observation of fluid inclusions in natural minerals whose salinities had already
      been determined using microthermometry. The detection limit of the present method
      is 1 NaCl-eq wt. %. The minimum size of fluid inclusions that produced well
      resolved spectra was approximately 30 microm. This method was applied to assess
      micro fluid inclusions in a natural diamond with cubic growth habit (cuboid). The
      salinity and residual pressure of those fluid inclusions were estimated
      respectively as 4.4 wt. % NaCl-eq and 0.6-0.8 GPa. The present method is
      complementary to Raman microscopy and microthermometry for the determination of
      salinity in fluid inclusions of geological samples.

PMID- 16613641
TI  - Partial least squares regression calibration for determining wax content in
      processed flax fiber by near-infrared spectroscopy.
AB  - The quality of flax fiber in the textile industry is closely related to the wax
      content remaining on the fiber after the cleaning process. Extraction by organic
      solvents, which is currently used for determining wax content, is very time
      consuming and produces chemical waste. In this study, near-infrared (NIR)
      spectroscopy was used as a rapid analytical technique to develop models for wax
      content associated with flax fiber. Calibration samples (n=11) were prepared by
      manually mixing dewaxed fiber and isolated wax to provide a range of wax content
      from 0 to 5%. A total of fourteen flax fiber samples obtained after a cleaning
      process were used for prediction. Principal component analysis demonstrated that
      one principal component is enough to separate the flax fibers by their wax
      content. The most highly correlated wavelengths were 2312, 2352, 1732, and 1766
      nm, in order of significance. Partial least squares models were developed with
      various chemometric preprocessing approaches to obtain the best model
      performance. Two models, one using the entire region (1100-2498 nm) and the other
      using the selected wavelengths, were developed and the accuracies compared. For
      the model using the entire region, the correlation coefficient (R2) between
      actual and predicted values was 0.996 and the standard error of prediction
      (RMSEP) was 0.289%. For the selected-wavelengths model, the R2 was 0.997 and
      RMSEP was 0.272%. The results suggested that NIR spectroscopy can be used to
      determine wax content in very clean flax fiber and that development of a low-cost
      device, using few wavelengths, should be possible.

PMID- 16613642
TI  - New methodology to obtain a calibration model for noninvasive near-infrared blood
      glucose monitoring.
AB  - This paper reports new methodology to obtain a calibration model for noninvasive
      blood glucose monitoring using diffuse reflectance near-infrared (NIR)
      spectroscopy. Conventional studies of noninvasive blood glucose monitoring with
      NIR spectroscopy use a calibration model developed by in vivo experimental data
      sets. In order to create a calibration model, we have used a numerical simulation
      of light propagation in skin tissue to obtain simulated NIR diffuse reflectance
      spectra. The numerical simulation method enables us to design parameters
      affecting the prediction of blood glucose levels and their variation ranges for a
      data set to create a calibration model using multivariate analysis without any in
      vivo experiments in advance. By designing the parameters and their variation
      ranges appropriately, we can prevent a calibration model from chance temporal
      correlations that are often observed in conventional studies using NIR
      spectroscopy. The calibration model (regression coefficient vector) obtained by
      the numerical simulation has a characteristic positive peak at the wavelength
      around 1600 nm. This characteristic feature of the regression coefficient vector
      is very similar to those obtained by our previous in vitro and in vivo
      experimental studies. This positive peak at around 1600 nm also corresponds to
      the characteristic absorption band of glucose. The present study has reinforced
      that the characteristic absorbance of glucose at around 1600 nm is useful to
      predict the blood glucose level by diffuse reflectance NIR spectroscopy. We have
      validated this new calibration methodology using in vivo experiments. As a
      result, we obtained a coefficient of determination, r2, of 0.87 and a standard
      error of prediction (SEP) of 12.3 mg/dL between the predicted blood glucose
      levels and the reference blood glucose levels for all the experiments we have
      conducted. These results of in vivo experiments indicate that if the parameters
      and their vibration ranges are appropriately taken into account in a numerical
      simulation, the new calibration methodology provides us with a very good
      calibration model that can predict blood glucose levels with small errors without
      conducting any experiments in advance to create a calibration model for each
      individual patient. This new calibration methodology using numerical simulation
      has promising potential for NIR spectroscopy, especially for noninvasive blood
      glucose monitoring.

PMID- 16613643
TI  - Near-infrared combination and overtone bands of the CH2 sequence in CH2X2,
      CH2XCHX2, and CH3(CH2)5CH3 and their characteristic frequency zones.
AB  - We characterized near-infrared spectra of the CH2 sequence in CH2X2 (X=halogen),
      CH2ClCHCl2, and CH3(CH2)5CH3. Each near-infrared absorption in the region from
      3500 to 10,000 cm-1 is consistently assigned to one of the five different
      combination or overtone groups, in the order of increasing frequency, of the
      {[v(CH)]+[delta(CH)]} (A), {[v(CH)]+[2delta(CH)]} (B), [2v(CH)] (C),
      {[2v(CH)]+[delta(CH)]} (D), and [3v(CH)] (E) types, where v(CH) and delta(CH)
      denote the CH stretching and CH deformation normal modes, respectively. Each
      group has its own characteristic frequency zone. The bands of B, D, and E, which
      are second-order combinations or overtones, are weaker by 1/10-1/50 than those of
      A and C, which are first-order combinations or overtones. The near-infrared
      spectra of the CH2 sequence show "window zones" of very weak or no absorptions.
      This suggests that we can perceive the characteristic near-infrared bands of a
      functional group through the window zones, and we give an example to demonstrate
      this. The first-order combination bands of type A only of CH2X2 are reasonably
      assigned to a pair of the normal modes of v(CH) and delta(CH). From this we
      predict that the first-order combination bands should give structural information
      on the CH2 chain, similar to the infrared fundamental bands.

PMID- 16613644
TI  - Multispectral polarization imaging for observing blood oxygen saturation in skin
      tissue.
AB  - We propose a new technique that combines two-dimensional (2D) multispectral
      imaging and polarization gating for observing the blood oxygen saturation (SpO2)
      level in human skin tissue. The spectral decomposition of the skin tissue image
      provides the principal information on blood oxygenation. The polarization gating
      selects the measurement depth according to the relative orientation of the two
      polarizers that are placed on a camera and a light source. The combination of
      these two methods yields multispectral images of the superficial and deep layers
      of the skin tissue separately. In order to evaluate the blood oxygen, we focus on
      the multispectral images of the deep site. The SpO2 levels at each image pixel
      are calculated by means of the partial least squares regression with respect to
      each reflectance spectrum. The reassignment of the predicted responses retrieves
      an image whose pixel values represent the relative SpO2 levels. A demonstration
      experiment for acquiring the multispectral polarization images is performed in
      the spectral range of 500 to 680 nm, and the SpO2 distributions are obtained.

PMID- 16613645
TI  - Comparison between two detection systems for fiber-optic chemical sensor
      applications.
AB  - Two optical detection system designs are compared for fiber-optic chemical sensor
      applications. A single grating spectrograph with fiber-optic input and
      photodiodes at three different wavelengths is compared to 1x3 fiber-optic
      splitters and photodiode detectors with integrated interference filters. The
      splitters are used to direct the optical power to the filter photodiodes. Three
      types of 1x3 commercially available splitters were tested: a 400 microm fused
      glass fiber-optic coupler, a 1000 microm fused plastic fiber-optic coupler, and a
      1000 microm glass fiber-optic bundle. This study finds that the fiber-splitter
      based detection systems have similar stray light, signal-to-noise ratio, and long
      term absorbance stability compared to the spectrograph detection system with a
      modest improvement in spectral resolution (from approximately 12 nm to
      approximately 6 nm). It is also much smaller in size and lower in cost.
      Applications of the two systems in a colorimetric CO2 partial pressure sensor are
      compared and similar accuracy and precision are achieved.

PMID- 16613646
TI  - Gender differences in social representations of aggression: the phenomenological
      experience of differences in inhibitory control?
AB  - Women are more likely than men to experience acts of aggression as expressive (a
      loss of self-control) than as instrumental (control over others). We propose that
      this might arise from differences in behavioural restraint. If women have better
      inhibitory control, aggressive behaviour should occur less frequently yet should
      be experienced as more emotionally 'out of control' because women can tolerate
      higher levels of anger before inhibitory control is breached. Participants (N =
      606) aged 13-24 completed the Multidimensional Personality Questionnaire (MPQ),
      the State-Trait Anger Expression Inventory-2 (STAXI-2) and Expagg. A more
      expressive view of aggression was associated with higher levels of STAXI anger
      control and higher levels of MPQ constraint. However, it was the harm avoidance
      component of constraint, rather than control versus impulsivity, that was the
      stronger predictor. While behavioural inhibition is built on an infrastructure of
      fear, the latter may be more important in explaining gender differences in social
      representations of aggression.

PMID- 16613647
TI  - The role of affect in UK commuters' travel mode choices: an interpretative
      phenomenological analysis.
AB  - Previous research has suggested that the choice between public transport and
      private car use is not solely based on utility considerations, such as time and
      cost. However, affective considerations tend not to be targeted in policy
      interventions to reduce car use. This may be due, in part, to a lack of clarity
      about which affective responses to car use are important and how they may affect
      willingness to switch to public transport. This study sought to clarify the role
      of affective responses in transport mode choice. An interpretative
      phenomenological analysis (IPA) of car users' accounts was conducted to (i)
      explore affect associated with decisions to drive or use public transport to get
      to work; and (ii) describe the role of affect on such transport decisions, and
      its relationship to utility considerations. Semi-structured interviews were
      conducted with 18 car users employed at a medium-sized UK university. Four affect
      themes were identified: These were journey-based affect (JBA), personal space,
      autonomy and identity. Typical 'utility' factors such as time, cost and
      reliability had important affective effects, and these were considered alongside
      utility components (e.g. getting to work on time). However, these effects were
      not always additive, and the role of affect depended on participants' own
      assessment of their circumstances. Implications for interventions are discussed.

PMID- 16613648
TI  - Schizotypy and creativity in visual artists.
AB  - 'Every work of art is an uncommitted crime' Adorno (1951). Cited in Julius
      (2002). Given the putative relationship between creativity and
      schizotypy/psychoticism, the current study set out to investigate differences in
      scores on a range of personality and creativity measures between visual artists
      and non-artists. Results found that the visual artists group scored higher on
      measures of positive-schizotypy, disorganized-schizotypy, asocial-schizotypy,
      neuroticism, openness and divergent thinking (uniqueness) than did the non-artist
      group and lower on agreeableness. These findings lend support to other studies
      reporting higher schizotypy scores in artistic and creative cohorts, although
      provide some of the first evidence of higher unusual experiences and impulsive
      nonconformity scores on the Oxford-Liverpool Inventory of Feelings and
      Experiences (O-LIFE) in visual artists. The relationship between creativity and
      schizotypy is discussed in terms of unusual ideas and a propensity to endorse
      socially undesirable responses.

PMID- 16613649
TI  - The orthographic uniqueness point and eye movements during reading.
AB  - Recent research found that naming and lexical decision times for words with an
      early orthographic uniqueness point (OUP) were faster than for words with a late
      OUP (Kwantes & Mewhort, 1999a; Lindell, Nicholls, & Castles, 2003). A word's OUP
      corresponds to the letter position in the word where that word is differentiated
      from other words. These results have been presented as evidence for sequential
      letter processing in visual word recognition (Kwantes & Mewhort, 1999a). In two
      experiments, we attempted to extend these results to a more natural reading
      situation by recording participants' eye movements. Readers read sentences with
      early or late OUP words embedded in them. In both experiments, we manipulated the
      amount of parafoveal information available during reading. Readers did not show
      any consistent benefit for reading words with an early OUP regardless of the
      amount of preview available. Our results are at odds with the naming and lexical
      decision data and prove problematic for models that predict OUP effects.

PMID- 16613650
TI  - Visuospatial working memory and the processing of spatial descriptions.
AB  - The dual-task paradigm was used to determine whether the spatial, visual and
      verbal components of working memory are engaged in the processing of spatial
      descriptions. Participants listened to route or survey descriptions of urban-like
      spatial environments and then drew corresponding maps. The position of each new
      landmark was described either in terms of the direction to move toward this
      landmark (route descriptions) or its relative location with regard to the
      previously mentioned landmark (survey descriptions). Route and survey
      descriptions resulted in similar recall performance in the absence of an
      interfering task and landmarks were consistently less well recalled than their
      associated moves/locations. The pattern of interference resulting from the
      secondary tasks indicated that the processing of landmarks called upon both the
      visual and spatial components of working memory in the route perspective, whereas
      the processing of moves/locations essentially relied on the spatial component in
      both the route and the survey perspectives. The verbal component of working
      memory was only involved in the processing of landmarks in the survey
      perspective. The results suggest that distinct cognitive processes support memory
      for route and survey descriptions, and that distinct working memory resources
      support the processing of landmarks and landmark positions.

PMID- 16613651
TI  - Segregation accuracy in item-method directed forgetting across multiple tests.
AB  - Two experiments examined recall across tests following item-method directed
      forgetting instructions and the varying of presentation duration of items at
      study. For both immediate testing (Experiment 1) and delayed testing (Experiment
      2), accurate recall of remember instruction items (R-items) exceeded the accurate
      recall of forget instruction items (F-items). However, some F-items from study
      were inaccurately recalled as R-items and R-items from study as F-items.
      Inaccurate recall persisted across tests for both immediate and delayed recall
      and increased across tests for immediate recall. We view the R-item advantage in
      accurate recall as consistent with the account they receive more rehearsal at
      study than do F-items. We view inaccurate recall as reflecting the bias to report
      items retrieved on an immediate test lacking instructional tags as F-items. On
      delayed tests, items retrieved lacking instructional tags are first assessed
      against a criterion point on a memory-strength continuum and those with strength
      above the criterion reported as R-items and those below the criterion as F-items.

PMID- 16613652
TI  - The effect of word and character frequency on the eye movements of Chinese
      readers.
AB  - Eye movements of native Chinese readers were monitored as they read sentences
      containing target words that varied in terms of word frequency and character
      frequency. There was an effect of word frequency on fixation times on a target
      word and it was comparable in size to that typically found with readers of
      English. Furthermore, character frequency also influenced fixation time on the
      target word. The effect of the initial character in two character words was more
      pronounced than that of the second character. However, word frequency modulated
      the effect of character frequency. The effect of character frequency was
      attenuated with high frequency target words while it was quite apparent with low
      frequency target words.

PMID- 16613653
TI  - The distinctiveness effect in forenames: the role of subjective experiences and
      recognition memory.
AB  - We describe two experiments that tested the prediction that distinctive forenames
      would be better recognized than typical forenames and which investigated whether
      this distinctiveness effect, if obtained, occurred in subjective experiences of
      the recollective or familiarity components of recognition memory. To that end,
      the remember-know paradigm was used to measure people's experiences of
      recollection or familiarity. The results revealed that distinctive forenames were
      more memorable than typical forenames and that that this distinctiveness effect
      was present only in the subjective experience of remembering. Additionally, the
      present research showed that these distinctiveness effects were present after
      retention intervals of both 1 and 7 days. These results replicate and extend past
      research on distinctiveness effects and also provide support for Rajaram's (1996)
      distinctiveness-fluency account of the 2 states of subjective awareness.

PMID- 16613654
TI  - Primary lymphoma of the nervous system.
AB  - This review article provides guidelines for the diagnosis, staging, and
      management of primary nervous system lymphoma based on the results of clinical
      trials conducted during the last decade. Recent progress in our understanding of
      the pathogenesis of primary nervous system lymphoma is summarized, and
      implications of these findings for the development of diagnostic tools and new
      therapeutic strategies are outlined. We performed a search of the PubMed database
      (National Center for Biotechnology Information) for articles on primary nervous
      system lymphoma published between 1970 and May 2005. Primary nervous system
      lymphoma affects the brain, eye, and meninges as well as cranial, spinal, and
      peripheral nerves. Although important lessons have been learned from the
      pathogenesis of extraneural non-Hodgkin's lymphoma, the unique organotropism of
      primary nervous system lymphoma remains poorly understood. Diagnosis is
      facilitated by modern imaging techniques and molecular markers. Clinically
      recognizable "precursors" may exist but frequently elude specific diagnosis.
      Insight into the peculiar pharmacokinetics of chemotherapy aimed at tumors within
      the nervous system has led to the development of methotrexate-based regimens that
      can achieve prolonged progression-free survival without the use of radiation.
      Long-term survival and, in selected cases, even a cure are possible in primary
      nervous system lymphoma. Treatment should be provided in specialized
      multidisciplinary centers. In spite of remarkable progress through methotrexate
      based chemotherapy, the majority of patients experience relapse within a few
      years. Better diagnostic tools are required for earlier diagnosis and monitoring
      of treatment response. A deeper understanding of the pathogenesis of primary
      nervous system lymphoma may reveal new therapeutic targets.

PMID- 16613655
TI  - Re-excision for ductal carcinoma in situ: the surgeon's least favorite operation.

PMID- 16613656
TI  - Rapid screening for EGFR mutations: pros and cons.

PMID- 16613657
TI  - Stereotactic body radiation therapy: a treatment in need of basic biological
      research.

PMID- 16613658
TI  - Hypercalcemia of malignancy remains a clinically relevant problem.

PMID- 16613659
TI  - Long-term outcome for mammographically detected ductal carcinoma in situ managed
      with breast conservation treatment: prognostic significance of reexcision.
AB  - BACKGROUND: The importance of negative final resection margins for optimal local
      control has been established for women with ductal carcinoma in situ (intraductal
      carcinoma) undergoing breast conservation treatment. This study evaluated long
      term outcome after breast conservation treatment and whether reexcision or the
      presence of residual tumor in the reexcision specimen predicted for local
      recurrence in patients with ductal carcinoma in situ with negative margins.
      METHODS: The study cohort consisted of 192 women with ductal carcinoma in situ
      treated with breast conservation treatment at the University of Pennsylvania from
      1978 to 2000. Analysis was performed for unilateral, mammographically detected,
      intraductal breast carcinomas. Study endpoints of interest included rates of
      local recurrence, overall survival, and cause-specific survival. The median
      follow-up was 6.2 years (mean, 7 years; range, 0.1-21.4 years). RESULTS: The 10
      year overall survival and 10-year cause-specific survival rates were 87% and 99%,
      respectively. There were 11 local failures (6%) in the treated breast, with a 10
      year actuarial local failure rate of 10% and a median time to local failure of
      7.4 years (mean, 6.6 years; range, 1.6-10.2 years). Among the subset of 124
      patients with negative final resection margins, there was no statistically
      significant difference in the 8-year actuarial local recurrence rates among
      patients who underwent single excision (7%), reexcision with residual tumor (8%),
      or reexcision with no residual tumor (0%). DISCUSSION: The use of breast
      conservation treatment in patients with ductal carcinoma in situ remains an
      effective and durable treatment approach. The need for reexcision to achieve
      negative margins and the presence of residual ductal carcinoma in situ in the
      reexcision specimen do not negatively impact local recurrence rates in the
      current study. These findings suggest that requiring more than one surgery to
      obtain clear resection margins is not an adverse prognostic factor for local
      failure.

PMID- 16613660
TI  - Rapid detection of epidermal growth factor receptor mutations in non-small cell
      lung cancer using real-time polymerase chain reaction with TaqMan-MGB probes.
AB  - We investigated somatic mutations of the epidermal growth factor receptor gene in
      non-small cell lung cancer tumor tissue and their detection using real-time
      polymerase chain reaction with TaqMan-MGB probes. METHODS: The DNA was extracted
      from surgically resected non-small cell lung cancer tumor specimens. Genes
      encoding for epidermal growth factor receptor tyrosine (exons 18, 19, and 21)
      were amplified by nested polymerase chain reaction, sequenced, and analyzed by
      chromatograms with manual review. TaqMan-MGB probes were designed to detect the
      epidermal growth factor receptor gene mutations in the tumor tissues using real
      time polymerase chain reaction. RESULTS: Somatic point mutations and deletions
      were identified in the tyrosine kinase domain of the epidermal growth factor
      receptor gene in 21 of 80 non-small cell lung cancer patients, including 13
      patients with deletion mutations occurring in exon 19 and 8 patients with point
      mutations occurring in codon 858 (exon 21). The results from real-time polymerase
      chain reaction with TaqMan-MGB probes were completely consistent with sequencing
      outcomes. Both the sensitivity and specificity for detecting the epidermal growth
      factor receptor gene mutations using real-time polymerase chain reaction with
      TaqMan-MGB probes were 100%. The mutation incidence was significantly higher in
      female patients, nonsmokers, and patients with adenocarcinoma than in male
      patients, smokers, and those with nonadenocarcinomas (P < 0.05). The mutations
      were not related to patient's age or tumor nodal metastasis staging. CONCLUSIONS:
      Somatic mutations of the epidermal growth factor receptor gene that develop in
      non-small cell lung cancer patients are more common in female patients,
      nonsmokers, and patients with adenocarcinoma. Real-time polymerase chain reaction
      using TaqMan-MGB probes is effective, simple, and fast in the detection of
      epidermal growth factor receptor gene mutations.

PMID- 16613661
TI  - Characteristics of patients who developed radiation pneumonitis requiring steroid
      therapy after stereotactic irradiation for lung tumors.
AB  - BACKGROUND: To find possible risk factors for symptomatic radiation pneumonitis
      (RP) after stereotactic irradiation (STI) for peripheral non-small cell lung
      cancer (NSCLC), pre-treatment pulmonary function test and dose volume statistics
      in patients who developed RP requiring steroid intake were retrospectively
      compared with statistics of those who did not develop RP. MATERIALS AND METHODS:
      From 1996 to 2002, 156 patients with Stage I NSCLC received STI at 5 hospitals in
      Japan. Of those patients, 12 were medicated with steroids for RP after treatment
      (RP group). For comparison, 31 patients were randomly selected from the remaining
      144 patients who received STI but did not receive steroids (control group).
      RESULTS: There were no statistical differences in age, sex, tumor size,
      performance status, forced expiratory volume in 1 sec (FEV1.0%), or percent vital
      capacity (%VC) between patients medicated with steroids for RP and those who did
      not have RP and received no steroids. V20 (%) was 7 to 18% (median 8%) in
      patients medicated with steroids for RP and 2 to 16% (median 7%) in those who did
      not have RP. No difference was observed in V20, the biologically effectively dose
      (BED) at the periphery of the planning target volume, or the dose per fraction
      between the two groups. CONCLUSIONS: Pre-treatment pulmonary function test (%VC,
      FEV1.0%), and dose volume statistics V20, total dose, BED, dose per fraction,
      peripheral dose) were not predictive of RP requiring steroid intake after STI for
      stage I NSCLC.

PMID- 16613662
TI  - Randomized, double-blind, phase II trial of gallium nitrate compared with
      pamidronate for acute control of cancer-related hypercalcemia.
AB  - BACKGROUND: Both gallium nitrate and pamidronate are highly effective for acute
      control of cancer-related hypercalcemia. However, the proportion of patients who
      actually achieve normocalcemia has varied in published reports. Therefore, we
      conducted an exploratory, randomized, double-blind trial that compared the
      efficacy and safety of gallium nitrate and pamidronate in hospitalized patients
      with cancer-related hypercalcemia. PATIENTS AND METHODS: Eligible patients with
      hypercalcemia, defined as albumin-adjusted serum calcium > or = 12.0 mg/dL after
      intravenous hydration, were stratified on the basis of tumor histology (i.e.,
      epidermoid or nonepidermoid) and by study site. Patients were then randomly
      assigned to receive intravenous gallium nitrate 200 mg/m2 daily for 5 days or
      intravenous pamidronate 60 mg (increased during the study to 90 mg for patients
      with initial serum calcium > or = 13.5 mg/dL) followed by placebo infusions for 4
      days. The primary endpoint of the study was comparison of the proportion of
      patients who achieved normocalcemia. RESULTS: Sixty-four patients were
      randomized, and all patients were evaluable for efficacy and safety.
      Normocalcemia was achieved in 22 of 32 (69%) patients treated with gallium
      nitrate compared with 18 of 32 patients (56%) treated with pamidronate. Patients
      randomized to pamidronate with initial serum calcium > or = 13.5 mg/dL did not
      respond better to 90 mg (3 of 6; 50%) than to 60 mg (7 of 13; 54%), or compared
      with the response to gallium nitrate in this subset (15 of 21; 71%). Response to
      pamidronate was also lower in patients with epidermoid cancers (33%, vs 68% for
      gallium nitrate). Duration of normocalcemia was examined using both an intent-to
      treat analysis irrespective of response and an analysis that examined only
      responding patients. By intent-to-treat analysis, the median duration of
      normocalcemia was 1 day for the pamidronate group and 7 days for the gallium
      nitrate group. Estimated normocalcemic duration in responders was 10 days for the
      pamidronate group and 14 days for the gallium nitrate group. Both drugs were well
      tolerated, and clinically significant nephrotoxicity was not observed in either
      treatment group. DISCUSSION: Gallium nitrate appears to be at least as effective
      as pamidronate for acute control of cancer-related hypercalcemia. Results from
      this trial suggest that gallium nitrate may be particularly useful in patients
      with epidermoid cancers or severe hypercalcemia at baseline, and in patients who
      have previously exhibited a poor response to bisphosphonates.

PMID- 16613663
TI  - Central neurologic involvement in mycosis fungoides: ten cases, actuarial risk
      assessment, and predictive factors.
AB  - BACKGROUND: Neurologic involvement in mycosis fungoides is rare. Isolated case
      reports in the literature suggest the pattern and the natural history for such
      occurrences, while a literature summary can provide direction on diagnosis and
      management. Although case series may confirm such information, cohort data are
      required to establish an overall risk of occurrence and to evaluate possible
      predictive factors. METHODS: We presented a case of central nervous system
      involvement in mycosis fungoides from Haifa, Israel and tabulated a series of
      nine cases from Canada. To estimate the risk of neurologic involvement, a cohort
      of 680 consecutive patients with newly diagnosed mycosis fungoides, of which the
      nine cases of neurologic involvement emerged during follow up, was analyzed using
      the Kaplan-Meier method. The actuarial risk of developing neurologic involvement
      was related to the baseline tumor-node-metastasis-blood classification factors.
      RESULTS: The pattern of disease in these 10 additional cases confirms the overall
      pattern in the approximately 40 patients described in the literature. The main
      symptoms are fluctuating higher cognitive functions and cranial nerve
      dysfunction, with fairly rapid clinical onset of symptoms. Most cases of central
      neurologic involvement with mycosis fungoides emerge within a setting of advanced
      disease. In patients with newly diagnosed mycosis fungoides, the greatest risk of
      developing neurologic involvement is within the first several years after
      diagnosis and is associated with the initial stage of disease. Patients with two
      or more of the T3-4, N3, M1, and B1 classification factors have a one in six
      chance of developing central neurologic involvement, while there is about a one
      in a hundred chance for the corresponding control group. CONCLUSIONS: Neurologic
      involvement with mycosis fungoides is indeed rare, but it is associated with a
      more advanced stage at diagnosis and with other visceral disease that can precede
      it. Although the role of low-dose prophylactic cranial radiation is uncertain,
      overt neurologic involvement requires urgent palliative treatment.

PMID- 16613664
TI  - Phase I trial of concomitant hyperfractionated radiotherapy with docetaxel and
      cisplatin for locally advanced head and neck cancer.
AB  - BACKGROUND: This study was conducted to determine the maximum tolerated dose of
      docetaxel when administered concomitantly with radical hyperfractionated
      radiotherapy and cisplatin in patients with locally advanced head and neck
      cancer. PATIENTS AND METHODS: Patients with stage III-IV tumors received radical
      radiotherapy of 74.4 Gy given in two daily fractions of 1.2 Gy for 6 weeks.
      Cisplatin was given once weekly on day 1 at a constant dose of 15 mg/m2. The
      starting dose of docetaxel was 10 mg/m2 once weekly on day 3, with planned
      escalation steps of 5 mg/m2. Main endpoints of the study were the maximum
      tolerated dose of docetaxel, acute toxicities, and the preliminary efficacy
      results. RESULTS: Twenty-five patients were enrolled. Median follow-up was 15
      months (range: 4-40 months). Two of three patients presented with dose-limiting
      toxicities at the 15-mg/m2 dose of docetaxel (one patient presented with multiple
      grade 3-4 toxicities requiring hospitalization for management and another
      presented with multiple toxicities including life-threatening bronchoaspiration).
      Thus, the weekly docetaxel dose of 10 mg/m2 was considered the maximum tolerated
      dose. Nineteen patients were then treated with the maximum tolerated dose and no
      dose-limiting toxicities were observed. Radiotherapy was completed in all
      patients except one (median dose: 74.4; range: 73.2-74.4), and at least 80% of
      the scheduled cisplatin and docetaxel doses were given in 92% of the patients.
      Acute toxicities were dominated by grade 3 mucositis (92%) and grade 3-4
      dysphagia (68%). The 2.5 year actuarial local control rate was 87.5%, and the
      disease-free survival rate was 75%. At the time of last follow-up, 23 patients
      were alive and two had died from cancer. No distant metastases were observed.
      DISCUSSION: In patients with locally advanced head and neck cancer, this study
      determined the maximum tolerated dose of docetaxel to be 10 mg/m2 administered
      once weekly when given concurrently with 74.4 Gy hyperfractionated radiotherapy
      and a weekly 15-mg/m2 dose of cisplatin. The toxicity profile and the encouraging
      results suggest that this new combination merits further investigation in a multi
      institutional phase II trial.

PMID- 16613665
TI  - The influence of granisetron on the pharmacokinetics and pharmacodynamics of
      docetaxel in Asian lung cancer patients.
AB  - BACKGROUND: Docetaxel, which undergoes hepatic metabolism via cytochrome P450
      3A4, is a promising anticancer agent. Toxicity is serious problem, however,
      because it is difficult to predict the cytochrome P450 3A4 activity of the drug.
      Moreover, drug-drug interactions involving cytochrome P450 3A4 enzymes are
      important. Granisetron, a selective antagonist of the 5-hydroxytryptamine3
      receptor, also undergoes hepatic metabolism via cytochrome P450 3A4. In this
      study, we investigated the influence of granisetron on the pharmacokinetics and
      pharmacodynamics of docetaxel in Asian patients with lung cancer. METHODS: Six
      patients with advanced lung cancer were treated with doses of docetaxel (60
      mg/m2). In the first course of treatment, no antiemetic agents were administered.
      In the second course, all patients received 3.0 mg of granisetron before 30
      minute administration of docetaxel. In each of the treatment courses, blood
      samples (5 mL) were obtained for pharmacokinetic study at the following times: 0,
      0.5, 1.5, 2.0, 3.0, 5.0, 8.0, and 24 hours after the start of the docetaxel
      infusion. RESULTS: Six patients were enrolled in this pharmacokinetics study. The
      mean +/- SD systemic clearance of docetaxel administered alone or in combination
      with granisetron was 32.9 +/ - 8.3 and 28.2 +/- 5.9, respectively. The area under
      the concentration-versus-time curve of plasma docetaxel (alone or in combination
      with granisetron) ranged from 1.355 to 2.773 and 1.647 to 3.079 microg x h/mL
      (mean +/- SD: 1.936 +/- 0.541 and 2.219 +/- 0.510 microg x h/mL), respectively.
      There was no significant difference in mean residence time (or invariance of
      residence time) between the single dose of docetaxel and the combination of
      docetaxel and granisetron. DISCUSSION: We found no significant difference in the
      pharmacokinetic and pharmacodynamic parameters of docetaxel between the single
      dose of docetaxel and the combination of docetaxel and granisetron. However, a
      wide interindividual variation existed in cytochrome P450 3A4 activity. It is
      clear that the results of the present study should be confirmed in a population
      study involving a larger number of subjects addressing the genetic variations of
      drug metabolizing enzymes, drug receptors, and drug transporters.

PMID- 16613666
TI  - Cancer diagnosis and treatment: communication accuracy between patients and their
      physicians.
AB  - BACKGROUND: We evaluated a patient's understanding of his or her cancer
      (diagnosis, location, stage, status) as a function of age, race, education,
      income, and marital status. METHODS: Patients with cancer were prospectively
      recruited and surveyed during their outpatient chemotherapy. Survey questions
      related to demographics, cancer status, location of cancer, stage of disease,
      prescribed treatment, the treating oncologist, and satisfaction with both the
      oncologist and medical staff. Each patient's answers to the survey questions were
      then compared with his or her medical chart. Data analysis was performed with the
      Chi-square test, logistic regression, and multivariate analysis. RESULTS: Study
      participants included 284 patients (38% male, 62% female) (56% African American,
      42% Caucasian, 3% others) with a median age of 62 years. Patients correctly
      answered in regards to their diagnosis (98%), cancer location (91%), and name of
      their doctor (99%). However, only 23% scored correctly when asked the stage of
      their cancer. In univariate analysis, younger age (P = 0.006) was the only
      significant variable in answering the question correctly, while higher income (P
      = 0.065) and female gender (P = 0.092) approached statistical significance. In
      multivariate analysis, all three variables were shown to be significant (P values
      of 0.016, 0.028, and 0.041, respectively). Increasing age resulted in a reduction
      of 2.5% per year, higher income resulted in an increase of 1.3% per 1000 dollars,
      and females were 49% more accurate, in the ability to correctly identify the
      cancer stage. DISCUSSION: Although patients seem to know their condition well,
      many of them do not understand the stage of their cancer. Older patients,
      patients with lower income, and male patients seem to have less understanding of
      the stage of their cancer.

PMID- 16613667
TI  - [Security of dual cancer-specific targeting vector and its cytotoxic effect when
      harbored].
AB  - BACKGROUND & OBJECTIVE: The xenograft tumor mass in nude mice could be completely
      eliminated using the targeting dual gene-virotherapy strategy. Now, the most
      important point is to improve its security. This study was to construct dual
      cancer-specific targeting adenovirus called TD55 to evaluate its security, and
      construct TD55-TRAIL to explore its antitumor effect. METHODS: Plasmid pTD55 was
      constructed through replacing E1A promoter with promoter of human telomerase
      reverse transcriptase and deleting E1B 55KD gene, and plasmid pTD55-TRAIL was
      constructed by inserting TRAIL gene into pTD55. Adenoviruses TD55 and TD55-TRAIL
      were obtained through homologous recombination in 293 cells. Cytotoxic effects of
      TD55 and TD55-TRAIL on human colon cancer cell lines SW620 and HCT116, human lung
      cancer cell line A549, and human embryonic lung cell lines MRC5 and WI38 were
      detected by crystal violet staining and MTT assay. Tumor cell apoptosis was
      detected by flow cytometry. RESULTS: Cytotoxic effects of TD55-TRAIL on MRC5 and
      WI38 cells were weaker than those of ZD55-TRAIL. The virus proliferation ability
      of ZD55-TRAIL in normal cells is 3-5 times stronger than those of TD55 and TD55
      TRAIL. The apoptosis rate of TD55-TRAIL-infected SW620 cells was 3.3 times as
      high as that of TD55-infected SW620 cells. CONCLUSIONS: TD55-TRAIL has better
      security than ZD55-TRAIL in normal cells. So, the security of medication will be
      improved with dual targeting vector TD55. TD55-harbored gene as TD55-TRAIL has
      stronger effect than TD55 in inducing apoptosis of tumor cells.

PMID- 16613668
TI  - [Survivin antisense RNA induces apoptosis and sensitizes ovarian cancer cell line
      SKOV3 to docetaxel].
AB  - BACKGROUND & OBJECTIVE: Survivin gene overexpresses in a variety of human tumors,
      and plays an important role in cell apoptosis and drug resistance of tumors. This
      study was designed to establish Survivin antisense RNA, and explore its effects
      on apoptosis of ovarian cancer cell line SKOV3 and sensitivity to docetaxel.
      METHODS: Survivin antisense eukaryotic expression vector anti-pcDNA3-svv was
      established, and transfected into SKOV3 cells by electroperforation. Positive
      clones (SKOV3-SVVanti) were screened out. Survivin mRNA was detected by reverse
      transcription-polymerase chain reaction (RT-PCR); Survivin protein was detected
      by Western blot. The effect of Survivin antisense RNA on apoptosis of SKOV3 cells
      was measured by flow cytometry and observed under electron microscope; its effect
      on sensitivity of SKOV3 cells to docetaxel was examined by MTT assay. RESULTS:
      The mRNA and protein levels of Survivin were obviously lower in SKOV3-SVVanti
      cells than in control cells. Terminal apoptosis changes were observed under
      electron microscope after transfection. The apoptosis rate was 19%. The 50%
      inhibitory concentration (IC50) of docetaxel was significantly lower for SKOV3
      SVVanti cells than for control cells [(13.3+/-2.2) ng/ml vs. (53.2+/-2.4) ng/ml,
      P<0.05]. CONCLUSION: Surivivin antisense RNA can induce apoptosis of SKOV3 cells,
      and sensitize SKOV3 cells to docetaxel.

PMID- 16613669
TI  - [Effect of survivin shRNA on chemosensitivity of human ovarian cancer cell line
      OVCAR3 to paclitaxel].
AB  - BACKGROUND & OBJECTIVE: Drug resistance is a major obstacle to the successful
      chemotherapy of ovarian cancer. Recent studies have shown overexpression of
      Survivin in ovarian cancer tissues and cell lines, which may play an important
      role in the drug resistance of ovarian cancer. This study was to explore the
      effects of Survivin short hairpin RNA (shRNA) on Survivin expression, apoptosis,
      and chemosensitivity of human ovarian cancer cell line OVCAR3. METHODS: OVCAR3
      cells were transfected with Survivin shRNA. Untransfected, lip-transfected, and
      mU6-transfected cells were set as controls. Reverse transcription-polymerase
      chain reaction (RT-PCR) was used to detect the expression of Survivin mRNA. Flow
      cytometry was applied to examine the expression of Survivin protein and cell
      apoptosis. MTT assay was used to examine the effect of Survivin shRNA on
      chemosensitivity of OVCAR3 cells. RESULTS: The mRNA and protein levels of
      Survivin were obviously lower in Survivin shRNA-transfected OVCAR3 cells than in
      untransfected cells, lip-transfected cells, and mU6-transfected cells 24 h after
      transfection. The apoptotic rates of OVCAR3 cells 12 h, 24 h, 36 h, 48 h after
      Survivin shRNA transfection were 20.7%, 31.9%, 39.0%, and 46.7%, respectively,
      that showed a time-dependent manner. The 50% inhibitory concentrations (IC50) of
      paclitaxel were (0.305+/-0.032) micromol/L for untransfected cells, (0.157+/
      0.031) micromol/L for lip-transfected cells, (0.175+/-0.010) micromol/L for mU6
      transfected cells, and (0.019+/-0.001) micromol/L for Survivin shRNA-transfected
      cells; and the IC50 of cisplatin were (9.410+/-0.796) micromol/L, (6.675+/-1.739)
      micromol/L, (6.930+/-1.273) micromol/L, and (7.862+/-0.081) micromol/L,
      respectively. Survivin shRNA increased the sensitivity of OVCAR3 cells to
      paclitaxel by 16 folds (P<0.01), but had no significant effect on the sensitivity
      to cisplatin (P>0.05). CONCLUSION: Sequence-specific shRNA targeting Survivin can
      suppress the expression of Survivin gene effectively in OVCAR3 cells, and
      sensitize OVCAR3 cells to paclitaxel, but has no significant effect on the
      sensitivity to cisplatin.

PMID- 16613670
TI  - [Enhancive effect of PLK1 gene silencing on sensitivity of K562/A02 cells to
      adriamycin].
AB  - BACKGROUND & OBJECTIVE: Polo-like kinase 1 (PLK1), an important cell cycle
      regulator, is highly expressed in many types of cancer, and is associated with
      oncogenesis, treatment effectiveness and prognosis. This study was to investigate
      the enhancive effect of small interference RNA (siRNA) targeting PLK1 gene on the
      sensitivity of K562/A02 cells to adriamycin (ADM). METHODS: siRNA plasmid vector
      specifically targeting PLK1 gene with enhanced green fluorescent protein (EGFP)
      was constructed and transfected into K562/A02 cells. The expression of PLK1 was
      detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western
      blot. The 50% inhibitory concentration (IC50) of ADM on K562/A02 cells was
      measured by MTT assay. Intracellular ADM accumulation and ADM-induced apoptosis
      of K562/A02 cells were detected by flow cytometry. RESULTS: After treatment with
      PLK1 siRNA, the mRNA and protein levels of PLK1 in K562/A02 cells were decreased
      by (61.9+/-2.5)% and (65.3+/-2.4)% of control. The relative reverse rate of
      sensitivity of K562/A02 cells to ADM was 67.8%. The intracellular accumulation of
      ADM was greatly increased, and ADM-induced apoptosis of K562/A02 cells was
      elevated from 11.33% to 54.39%. CONCLUSION: PLK1 gene silencing could enhance
      intracellular ADM accumulation in K562/A02 cells, improve sensitivity of K562/A02
      cells to ADM, and induce cell apoptosis, therefore, reverse cell resistant to
      ADM.

PMID- 16613671
TI  - [Effects of suramin in combination with cisplatin on growth and metastasis of
      lung adenocarcinoma xenografts in mice].
AB  - BACKGROUND & OBJECTIVE: Recent study found angiogenesis plays some important
      roles in tumor growth and metastasis. This study was to explore the inhibitory
      effect of angiogenesis inhibitor Suramin in combination with cisplatin (DDP) on
      the growth and lung metastasis of lung adenocarcinoma LA795 cell xenografts in
      mice. METHODS: Highly metastatic LA795 cells were inoculated into the mammary
      fatty pad of 32 T739 mice to establish lung adenocarcinoma models. Four days
      after inoculation, the mice were randomized into 4 groups: the mice in control
      group received intraperitoneal injection of 0.2 ml normal saline everyday; the
      mice in DDP group received injection of DDP [2 mg. (kg.day)-1] at the 4th, 11th,
      and 18th days; the mice in Suramin group received injection of Suramin [10 mg.
      (kg.day)-1] everyday; the mice in combination group received injection of DDP [2
      mg. (kg.day)-1] at the 4th, 11th, and 18th days, and Suramin [10 mg. (kg day)-1]
      everyday. All mice were killed 24 days later. Lung and subcutaneous tumors were
      examined histologically. The metastatic tumor foci on lung surface were observed,
      lung weight was measured, the occurrence rate of lung metastasis and the
      inhibitory rate of metastatic foci were calculated, subcutaneous tumor
      microvessel density (MVD), vascular endothelial growth factor (VEGF), and nuclear
      factor-kappaB (NF-kappaB) were determined by immunohistochemistry, and tumor cell
      apoptosis was measured by TUNEL method. RESULTS: In DDP, Suramin, and combination
      groups, tumor growth was suppressed significantly, with growth inhibitory rates
      of 23.0%, 34.4%, and 56.3%, respectively (P<0.05). Necrosis and decrease of tumor
      vessels were observed in Suramin and combination groups. The expression of NF
      kappaB was significantly lower and tumor cell apoptosis index was significantly
      higher in DDP, Suramin, and combination groups than in control group (P<0.01).
      The metastatic foci on lung surface were less in Suramin and combination groups
      than in DDP and control groups. The expression of MVD and VEGF in subcutaneous
      tumors and the occurrence rate of lung metastasis were also obviously lower in
      Suramin and combination groups. CONCLUSION: Suramin has synergetic inhibitory
      effect with DDP on growth and metastasis of lung adenocarcinoma LA795 cell
      xenografts in mice through inhibiting angiogenesis and inducing cell apoptosis.

PMID- 16613672
TI  - [Inhibitory effects of cyclooxygenase-2 inhibitor celecoxib on growth and
      angiogenesis of human liver cancer HepG2 cell xenografts in small nude mice].
AB  - BACKGROUND & OBJECTIVE: Cyclooxygenase-2 (COX-2) is closely correlated to genesis
      of tumors, particularly digestive tract tumors, and its inhibitor has antitumor
      effect. This study was to investigate the inhibitory effects of COX-2 inhibitor
      celecoxib on growth and angiogenesis of human liver cancer HepG2 cell xenografts
      in small nude mice. METHODS: HepG2 cells were transplanted into the dorsal
      subcutaneous tissue of athymic nude mice. The mice were treated with celecoxib 4
      days after transplantation, and were killed 58 days later. Tumor volume and
      weight were measured. The expression of COX-2, vascular endothelial growth factor
      (VEGF), basic fibroblast growth factor (bFGF), and angiopoietin-2 (Ang-2) were
      detected by immunohistochemistry and reverse transcription-polymerase chain
      reaction (RT-PCR), and microvessel density (MVD) was observed by
      immunohistochemistry. RESULTS: The average tumor volume was significantly smaller
      and the average tumor weight was significantly lighter in celecoxib group than in
      control group [(709.11+/-108.53) mm3 vs. (1,417.55+/-69.50) mm3, and (2.63+/
      0.34) g vs. (5.32+/-0.98) g, P<0.01]. The inhibitory rate of tumor growth was
      55.21%. The expression levels of COX-2, VEGF, bFGF and Ang-2, and MVD were
      significantly lower in celecoxib group than in control group (2.43+/-0.29 vs.
      4.50+/-0.25, 2.80+/-0.30 vs. 5.49+/-0.58, 2.23+/-0.41 vs. 4.03+/-0.47, 2.88+/
      0.25 vs. 5.53+/-0.54, and 29.27+/-1.52 vs. 128.24+/-9.82, P<0.01, respectively).
      COX-2 expression was positively correlated to VEGF, bFGF and Ang-2 expression and
      MVD (r=0.862, r=0.882, r=0.857, r=0.837,P<0.01, respectively). CONCLUSIONS:
      Celecoxib inhibits the growth and angiogenesis of HepG2 cell xenografts in nude
      mice effectively via suppressing the expression of COX-2.

PMID- 16613673
TI  - [Inhibitory effect of human mitochondria-targeted MPG recombinant on
      proliferation of human non-small cell lung cancer multidrug-resistant cell line
      A549/DDP].
AB  - BACKGROUND & OBJECTIVE: Multidrug resistance is the key obstacle to the
      improvement of chemotherapy effect of lung cancer. This study was to construct
      eukaryotic expression vector of human mitochondria-targeted N-methylpurine DNA
      glycosylase (MPG), and explore its inhibitory effect on proliferation of human
      non-small cell lung cancer multidrug-resistant cell line A549/DDP. METHODS:
      Manganese-superoxide dismutase mitochondria-targeted sequence-MPG fusion gene
      (mito-MPG) was constructed through splicing by overlap extension (SOE).
      Recombinant eukaryotic expression vector pCMV-Script/mito-MPG was constructed by
      molecule-cloning technique, and then transfected into A549/DDP cells. In the
      stably transfected cells which were screened out by G418, the expression of mito
      MPG mRNA was detected by reverse transcription-polymerase chain reaction (RT
      PCR); its expression in separated and purified mitochondria was detected by
      Western blot. The proliferation of A549/DDP cells was detected by trypan blue
      exclusion trial. Cell cycle distribution was analyzed by flow cytometry. RESULTS:
      The mito-MPG fusion gene was confirmed by DNA sequencing,the recombinant pCMV
      Script/mito-MPG was confirmed by restrictive endonuclease digestion and DNA
      sequencing. mito-MPG mRNA and protein were detected in the cells transfected with
      pCMV-Script/mito-MPG (MPG group), but not in the cells transfected with pCMV
      Script (P group) and untransfected cells (C group). The cell double time were
      72.6 h in C group, 73.5 h in P group, and 98.9 h in MPG group. Cell cycle
      blockage and subdiploid peak were found in MPG group. The proliferation indexes
      were 51.3% in C group, 54.3% in P group, and 26.1% in MPG group. CONCLUSION: pCMV
      Script/mito-MPG could be constructed and transfected into mitochondria of
      A549/DDP cells successfully, and inhibit proliferation and induce apoptosis of
      A549/DDP cells.

PMID- 16613674
TI  - [The role of reactive oxygen species in cisplatin-induced apoptosis of esophageal
      cancer cell line EC-109].
AB  - BACKGROUND & OBJECTIVE: Reactive oxygen species (ROS), in vivo oxygen metabolites
      and important signaling molecules, play a vital role in cell apoptosis. This
      study was to investigate the role of ROS in cisplatin (DDP)-induced apoptosis of
      esophageal cancer cell line EC-109, and explore the mechanism. METHODS: EC-109
      cells were treated with different concentrations (0, 1, 5, 10, and 15 microg/ml)
      of DDP. MTT assay was used to evaluate the influence of DDP on cell
      proliferation. Flow cytometry was used to test ROS levels, intracellular
      mitochondrial transmembrane potential (Delta psi m), and hypodiploid apoptosis
      peak in EC-109 cells. Cell apoptosis after pretreatment with hydrogen peroxide
      scavenging enzyme catalase (CAT) was also detected. RESULTS: DDP obviously
      suppressed proliferation of EC-109 cells. When treated with 0, 1, 5, 10, 15
      microg/ml of DDP for 2 h, ROS levels were (3.3+/-1.0)%, (21.6+/-2.0)%, (32.6+/
      3.2)%, (44.7+/-2.2)%, and (53.1+/-3.6)%, respectively; when treated for 12 h,
      Delta psi m were (97.2+/-1.9)%, (90.6+/-1.9)%, (85.5+/-1.4)%, (67.8+/-2.0)%, and
      (62.4+/-3.0)%, respectively; when treated for 24 h, cell apoptotic rates were
      (3.4+/-1.2)%, (16.2+/-2.3)%, (28.1+/-1.5)%, (33.2+/-3.9)%, and (45.5+/-3.8)%,
      respectively. Pretreatment with CAT significantly rescued cells from apoptosis
      (P<0.05). CONCLUSION: DDP generates ROS in esophageal cancer EC-109 cells, which
      causes mitochondrial membrane permeabilization and Delta psi m decrease,
      therefore, leads to apoptosis of EC-109 cells.

PMID- 16613675
TI  - [Mechanisms of inhibiting proliferation and inducing apoptosis of human gastric
      cancer cell line SGC7901 by ursolic acid].
AB  - BACKGROUND & OBJECTIVE: Some studies have showed that ursolic acid (UA) can
      inhibit proliferation and induce apoptosis of many tumor cell lines, however its
      effect on gastric cancer cells has rarely been reported. Cyclooxygenase-2 (COX-2)
      is highly expressed in various precursor lesions and cancerous tissues. This
      study was to investigate the effect of UA on COX-2, Bcl-2 and Bax expression in
      human gastric cancer cell line SGC7901, and explore its potential mechanisms of
      inhibiting proliferation and inducing apoptosis. METHODS: MTT assay was used to
      observe the effect of UA (0, 10, 20, 30, 40 micromol/L) on proliferation of
      SGC7901 cells. Cell apoptosis was observed by fluorescence microscopy when
      treated with UA for 24 h. Cell cycle and apoptosis were analyzed by flow
      cytometry (FCM). The expression of COX-2, Bcl-2 and Bax was detected by Western
      blot. The level of prostaglandin E2 (PGE2) was measured by radioimmunoassay
      (RIA). RESULTS: UA (20-40 micromol/L) significantly inhibited the proliferation
      of SGC7901 cells in dose-and time-dependent manners, the IC50 value of UA at 12
      h, 24 h, 36 h, 48 h were (57.50+/-1.18) micromol/L, (34.28+/-2.05) micromol/L,
      (27.54+/-1.11) micromol/L, and (24.83+/-1.02) micromol/L, respectively. When
      treated with 20-40 micromol/L UA for 24 h, SGC7901 cells were arrested at G0/G1
      phase, and the apoptosis rates were (9.10+/-2.39)%, (26.30+/-1.25)%, and (35.20+/
      2.26)%, respectively; meanwhile, COX-2 expression and its catalysate PGE2 were
      decreased, Bcl-2 expression was also decreased, whereas Bax expression was
      unchanged. CONCLUSION: UA could inhibit proliferation and induce apoptosis of
      SGC7901 cells through arresting cell cycle, inhibiting COX-2 expression to reduce
      PGE2 production and down-regulate Bcl-2 expression.

PMID- 16613677
TI  - [Effects of interferon-gamma on Her-2/neu expression and antitumor activity of
      131I-Herceptin in breast cancer cell lines].
AB  - BACKGROUND & OBJECTIVE: Herceptin plays an important role in treating metastatic
      breast cancer by targeting Her2/neu, therefore, combining Herceptin with iodine
      131 (131I) might enhance its antitumor activity. This study was to up-regulate
      Her2/neu expression by interferon-gamma (IFN-gamma), and explore its effect on
      binding and antitumor activity of 131I-Herceptin in breast cancer cell lines MCF
      7, SKBR-3 and BT-474. METHODS: MCF-7, SKBR-3 and BT-474 cells were cultured with
      or without IFN-gamma (500 U/ml) for 48 h. The positive rate and mean fluorescence
      intensity (MFI) of Her2/neu on the 3 cell lines were tested by flow cytometry.
      Herceptin was labeled with 131I by Iodogen method, and its radiochemical purity
      (RCP) was tested by size-exclusion high-pressure liquid chromatography (HPLC).
      The binding rate of 131I-Herceptin on cells was measured by non-competitive
      saturation analysis, and its killing effect was estimated by colony-forming
      assay. The positive rate and MFI of Her2/neu, binding rate of 131I-Herceptin, and
      colony-forming rate were compared between IFN-gamma-induced group and control
      group by t test. RESULTS: For MCF-7 cells, the positive rate and MFI of Her2/neu
      were significantly higher in IFN-gamma-induced cells than in control cells
      [(15.2+/-4.7)% vs. (8.5+/-1.9)%, t=3.515, P<0.05; 121+/-17 vs. 38+/-7, t=7.823,
      P<0.002]; for SKBR-3 and BT-474 cells, no obvious difference of Her2/neu positive
      rate was observed between IFN-gamma-induced cells and control cells [(99.7+/
      0.9)% vs. (98.9+/-1.1)%, P>0.05; (99.5+/-1.2)% vs. (98.1+/-0.9)%, P>0.05], but
      the MFI of Her2/neu was significantly higher in IFN-gamma-induced cells than in
      control cells (1,608+/-201 vs. 952+/-125, t=4.802, P<0.01; 1,968+/-192 vs.
      1,020+/-98, t=7.614, P<0.002). The binding rates of Her2/neu were increased from
      (5.2+/-1.4)% to (12.3+/-3.4)% by 2.4 folds in MCF-7 cells, from (35.8+/-4.5)% to
      (48.9+/-7.1)% by 1.4 folds in SKBR-3 cells, and from (37.2+/-3.6)% to (59.5+/
      8.7)% by 1.6 folds in BT-474 cells after inducement with IFN-gamma. The colony
      forming rates were significantly lower in IFN-gamma-induced MCF-7, SKBR-3 and BT
      474 cells than in control cells [(30+/-4)% vs. (49+/-3)%, t=6.574, P<0.05; (23+/
      5)% vs. (37+/-6)%, t=3.105, P<0.05; (19+/-6)% vs. (34+/-5)%, t=3.323, P<0.05].
      CONCLUSION: IFN-gamma can up-regulate Her-2/neu expression and increase the
      binding of 131I-Herceptin, hence, improve the inhibitory effect of 131I-Herceptin
      on proliferation of breast cancer cells.

PMID- 16613676
TI  - [Inducement effect of synthetic indiosides from Solanum indicum L.on apoptosis of
      human hepatocarcinoma cell line Bel-7402 and its mechanism].
AB  - BACKGROUND & OBJECTIVE: Solanum indicum L., an anti-inflammatory and wound
      healing herb in traditional Chinese medicine, is enriched of unique dioscins,
      that is, indiosides. Our previous studies revealed that several synthetic
      indiosides from Solanum indicum L. have potent anticancer effects. This study was
      to investigate the anticancer mechanism of synthetic indiosides I from Solanum
      indicum L. METHODS: Human hepatocarcinoma Bel-7402 cells were treated with
      different concentrations of indiosides. The inhibitory rate of cell proliferation
      and 50% inhibitory concentration (IC50) of indiosides were detected by the acid
      phosphatase assay (APA). Cell morphology was observed under optical microscope
      with crystal violet staining. The expression of apoptosis-related proteins was
      detected by Western blot. RESULTS: Indiosides significantly inhibited
      proliferation of Bel-7402 cells: when treated with indioside I for 72 h, the IC50
      value was 4.2 microg/ml, cell density was decreased, and bubbles were observed in
      cytoplasm. Western blot showed that the cytoplasmic level of cytochrome c was
      increased significantly, Caspase-3 was activated, and poly (ADR-ribose)
      polymerase (PARP) was cleavaged after indioside I treatment. CONCLUSION:
      Indiosides have dose-dependent inhibitory effect on proliferation of Bel-7402
      cells, and can induce cell apoptosis through mitochondria-dependent pathway.

PMID- 16613678
TI  - [Inhibitory effects of iressa on hepatocellular carcinoma Hep-3B and HepG2 cell
      xenografts in nude mice].
AB  - BACKGROUND & OBJECTIVE: Iressa, a new molecular targeting medicine, has some
      effects on advanced non-small cell lung cancer, but its effect on hepatocellular
      carcinoma (HCC) has seldom been reported. This study was to observe the efficacy
      and adverse effect of Iressa on HCC Hep-3B and HepG2 cell xenografts in nude
      mice. METHODS: The nude mice with Hep-3B and HepG2 cell xenografts were
      randomized into control group (8 mice), low-dose group (8 mice), and high-dose
      group (8 mice), and received daily oral gavage of 5% glucose solution, 100 mg/kg
      Iressa, and 200 mg/kg Iressa, respectively, by 5 days each week for 3 weeks. The
      mice were killed 2 days after treatment. Inhibitory rate (IR) of tumor growth was
      calculated. Tumor volume, mice weight, and spleen index (SI) were compared
      between groups. RESULTS: Body weight and tumor volume of the mice were caparable
      before treatment. IRs of Hep-3B cell xenograft growth were 32.77% in low-dose
      group and 46.99% in high-dose group; IRs of HepG2 cell xenograft growth were
      68.57% and 75.24%, respectively. Body weight and SI of nude mice with either Hep
      3B or HepG2 cell xenografts were significantly lower in high-dose group than in
      control group, but no obvious difference was observed between low-dose group and
      control group. CONCLUSION: Iressa has obvious inhibitory effects on growth of
      both Hep-3B and HepG2 cell xenografts in nude mice, but high-dose (200 mg/kg) of
      Iressa may cause body weight lose and immunologic inhibition.

PMID- 16613679
TI  - [Inhibitory effects of tetraethylammonium on proliferation and voltage-gated
      potassium channels in human cervical carcinoma cell line SiHa].
AB  - BACKGROUND & OBJECTIVE: Various potassium channels are known to be involved in
      proliferation of many malignant cell lines. This study was to explore the role of
      voltage-gated potassium channels in proliferation of human cervical carcinoma
      cells through observing the effects of tetraethylammonium (TEA) on proliferation
      and outward potassium currents in human cervical carcinoma cell line SiHa.
      METHODS: SiHa cells were treated with TEA. The effect of TEA on proliferation of
      SiHa cells was assessed by MTT assay. Cell apoptosis and cell cycle were detected
      by flow cytometry with Hoechst 33258 staining. The outward potassium currents
      were recorded by patch clamp technique. RESULTS: TEA inhibited the proliferation
      of SiHa cells in dose-and time-dependent manners, and induced cell apoptosis. The
      cell cycle was arrested at G0/G1 phase after treatment with TEA. Exposure of SiHa
      cells to 10 mmol/L TEA reduced the peak outward potassium currents significantly
      from (260+/-12) pA to (58+/-6) pA (P<0.01). CONCLUSIONS: Voltage-gated potassium
      channels play an important role in regulating proliferation of cervical carcinoma
      SiHa cells. Blocking voltage-gated potassium channels could inhibit proliferation
      of SiHa cells.

PMID- 16613680
TI  - [In vitro killing effects of STI571 on esophageal carcinoma cell lines CE-48T and
      CE-81T].
AB  - BACKGROUND & OBJECTIVE: Tyrosine kinase mediates cell proliferation and
      differentiation, and plays important roles in tumorigenesis and development of
      esophageal carcinoma. STI571 is a tyrosine kinase inhibitor of platelet-derived
      growth factor receptor beta (PDGFR-beta) which is overexpressed in esophageal
      carcinoma. This study was to explore the in vitro killing effects of STI571 on
      esophageal carcinoma cell lines CE-48T and CE-81T. METHODS: The expression of
      PDGFR-alpha and PDGFR-beta in CE-48T and CE-81T cells was detected by Western
      blot. The killing effects of STI571 on CE-48T and CE-81T cells were evaluated by
      MTT assay. Cell apoptosis was analyzed by flow cytometry with Annexin V/PI
      labeling. The expression of p-PDGFR-beta was detected by Western blot before and
      after treatment of STI571. RESULTS: CE-48T cells expressed PDGFR-beta, but did
      not express PDGFR-alpha; CE-81T cells did not express both PDGFR-alpha and PDGFR
      beta. The 50% inhibitory concentration (IC50) of STI571 was significantly lower
      for CE-48T cells than for CE-81T cells [(8.32+/-1.50) micromol/L vs. (41.02+/
      7.64) micromol/L, P=0.002]. When treated with 10 micromol/L STI571 for 12 h, the
      apoptosis rate of CE-48T cells was (52.43+/-5.30)%, but the apoptosis rate did
      not increase as the treatment time and concentration increased. After treatment
      of STI571, the expression of p-PDGFR-beta was inhibited in CE-48T cells, but
      didn't change in CE-81T cells. CONCLUSIONS: STI-571 could induce the apoptosis of
      PDGFR-beta-positive esophageal carcinoma CE-48T cells. p-PDGFR-beta might be the
      target of STI571.

PMID- 16613681
TI  - [Prognostic analysis and assessment on the clinical staging systems of multiple
      myeloma--a report of 206 cases].
AB  - BACKGROUND & OBJECTIVE: Multiple myeloma (MM) is a heterogeneous disease of
      plasma cell tumor with poor prognosis. This study was to explore the prognostic
      factors of MM in China, and find the most suitable clinical staging systems.
      METHODS: Univariate and multivariate analyses were carried out on 18 clinical and
      laboratory indexes from 206 MM patients. These MM patients were classified
      according to 4 staging systems to compare their survival status. RESULTS: Of the
      206 patients, 138 were men and 68 were women, with median age of 59 years (ranged
      27-90 years) and median survival time of 33 months. The 2-and 5-year survival
      rates were 64.7% and 33.7%. Univariate analysis identified 10 prognostic factors:
      age, the amount of bone marrow plasma cells, hemoglobin, platelet count, adjusted
      serum calcium, albumin, creatinine, beta2 microglobulin, C-reactive protein, and
      skeletal disease stage. Multivariate analysis showed that C-reactive protein,
      beta2 microglobulin, albumin, age were independent prognostic factors.
      Significant differences of survival period existed among the 3 groups classified
      according to Durie Salmon staging system and Bataille staging system as well as
      between group I and group II of International staging system. However, no
      significant difference was found among the 3 groups classified according to
      British Medical Research Council staging system and between group II and group
      III of International staging system. CONCLUSIONS: High level of C-reactive
      protein, high level of beta2 microglobulin, low level of albumin and old age are
      correlated to poor prognosis. Durie Salmon staging system and Bataille staging
      system are suitable for Chinese MM patients.

PMID- 16613682
TI  - [Prognostic factors of primary non-Hodgkin's lymphoma of the nasal cavity--a
      report of 129 cases].
AB  - BACKGROUND & OBJECTIVE: The prognosis of primary non-Hodgkin's lymphoma (NHL) of
      the nasal cavity was poor, and the distant metastasis and local relapse rates are
      high. This study was to analyze the prognostic factors of this disease. METHODS:
      Clinical data of 129 patients with pathologically confirmed nasal NHL, treated
      from Jan. 1996 to Dec. 2002, were retrospectively reviewed. Of the 129 patients,
      116 were diagnosed as nasal NK/T-cell lymphoma. According to the Ann Arbor
      staging system, 102 patients had stage IE disease, 22 stage IIE, and 5 stage IVE.
      Among the 124 patients with stage IE or IIE disease, 22 received radiotherapy
      alone, 7 received chemotherapy alone, and 95 received combined modality therapy
      (CMT). Of the patients received CMT, 45 received radiotherapy followed by
      chemotherapy, and 50 received chemotherapy followed by radiotherapy. The stage
      IVE patients received chemotherapy with or without radiotherapy. RESULTS: The 5
      year overall survival (OS) and disease-freely survival (DFS) rates for all
      patients were 68.0% and 55.8%, respectively. The 5-year OS and DFS rates were
      71.7% and 60.9% for stage IE patients, and 70.6% and 47.0% for stage IIE
      patients, respectively (P>0.05). The 5-year OS and DFS rates were significantly
      higher in the patients who achieved complete response (CR) than in those who
      didn't (83.1% vs. 18.0%, 68.0% vs. 15.5%, P<0.01). The 5-year OS rates of the
      patients with international prognostic index (IPI) score of 0, 1, and > or =2
      were 81.1%, 60.1%, and 14.3% (P<0.01), respectively; the 5-year DFS rates were
      68.8%, 44.6%, and 22.5% (P<0.01), respectively. Thirty-eight patients developed
      progression or relapse, with distant extranodal dissemination (78.9%) as the
      primary pattern of failure. Univariate analysis showed that CR rate, PS, IPI, and
      modified IPI were related to prognosis. Multivariate analysis showed that CR rate
      was an independent prognostic factor. CONCLUSIONS: CR rate after treatment is an
      important prognostic factor of nasal NHL. Distant metastasis is the main failure
      pattern of nasal NHL.

PMID- 16613683
TI  - [Clinical analysis of reactive thymic hyperplasia following chemotherapy for
      childhood malignant lymphoma].
AB  - BACKGROUND & OBJECTIVE: Reactive thymic hyperplasia following chemotherapy for
      malignant tumors is likely to be misdiagnosed as tumor residue or relapse,
      therefore, leads to unnecessary treatment. This study was to analyze the clinical
      features of reactive thymic hyperplasia following chemotherapy for childhood
      malignant lymphoma. METHODS: Clinical data of 13 children with reactive thymic
      hyperplasia following chemotherapy for malignant lymphoma, treated from Mar. 1999
      to Mar. 2004, were retrospectively analyzed. Of the 13 cases, 5 were Hodgkin's
      disease (HD), and 8 were non-Hodgkin's lymphoma (NHL). All patients received
      computed tomography (CT) to evaluate the therapeutic effect. When a new thymic
      mass emerged, positive electron tomography/computed tomography (PET/CT) was
      performed to identify its quality. RESULTS: At diagnosis, 10 patients had
      mediastinal involvement. Reactive thymic hyperplasia occurred following the
      completion of chemotherapy in 9 cases, or during the maintenance of chemotherapy
      in 4 cases. CT showed that the longest diameters of the new mediastinal masses
      were 2.2-6.0 cm (mean 3.7 cm). The interval from last chemotherapy cycle to the
      occurrence of thymic hyperplasia was 2-12 months (mean 4 months). PET/CT was
      performed to 5 cases, and showed no vital tumors in the mediastinum. Three cases
      were misdiagnosed as tumor residue or relapse, and received second-line therapy.
      All patients were followed-up for 1-6 years (median 4 years), and none suffered
      tumor relapse. CONCLUSIONS: Reactive thymic hyperplasia may occur following
      intensive chemotherapy for childhood malignant lymphoma. It should not be
      misdiagnosed as malignant tumors and overtreated.

PMID- 16613684
TI  - [Primary central nervous system lymphoma--a report of 32 cases with literature
      review].
AB  - BACKGROUND & OBJECTIVE: The incidence of primary central nervous system lymphoma
      (PCNSL) is increasing, and its prognosis is poor. This study was to investigate
      the clinical features of PCNSL, and evaluate the efficacy of high-dose
      methotrexate (MTX)-based chemotherapy for immunocompetent Chinese patients with
      PCNSL. METHODS: Clinical data of 32 patients (median age, 50 years) with
      pathologically confirmed PCNSL were analyzed retrospectively. Before Nov. 2001,
      CHOP with or without whole brain radiotherapy (WBRT) was employed; after then,
      high-dose MTX-based chemotherapy with or without WBRT was employed. RESULTS: Of
      the 32 PCNSL patients, 25 (78.1%) were more than 45 years old; 24 (75.0%)
      suffered intracranial hypertension; 25 (78.1%) had single intracranial mass; no
      positive case of cerebrospinal fluid (CSF) cellular examination was found; 28
      (87.5%) were B-cell lymphoma, among which 19 (59.4%) were diffuse large B-cell
      lymphoma. Median follow-up of the patients was 13.5 months (1-84 months). Kaplan
      Meier test showed that the median overall survival time was 26 months, and the 2
      year survival rate was 45.7%. The complete response rate of the 18 patients who
      received high-dose MTX-based chemotherapy plus WBRT was 61.1%, the median
      survival time was more than 26 months, and the 2-year survival rate was 65.1%.
      The efficacy of high-dose MTX-based chemotherapy plus WBRT was better than that
      of CHOP plus WBRT. Log-rank test showed that the survival time of the patients
      with performance status (PS) of 0-1 or normal serum lactate dehydrogenase (LDH)
      was longer than those with PS of 2-3 or elevated LDH. CONCLUSIONS: PCNSL often
      occurs in middle-aged and aged patients, with intracranial hypertension as the
      main clinical manifestation. B-cell lymphoma is the predominant subtype. High
      dose MTX-based chemotherapy plus WBRT is efficient and feasible for PCNSL.

PMID- 16613685
TI  - [Clinical features of 89 patients with primary non-Hodgkin's lymphoma of the
      tonsil].
AB  - BACKGROUND & OBJECTIVE: Head and neck lymphoma develops predominantly in the
      tonsil. This study was to investigate the clinical features of primary non
      Hodgkin's lymphoma (NHL) of the tonsil, and to explore possible ways to improve
      the prognosis and quality of life of the patients after treatment. METHODS:
      Clinical data of 89 naive patients with NHL of the tonsil, treated from May 1990
      to Jan. 2003, were retrospectively reviewed. All patients were confirmed
      pathologically and classified according to revised European-American Lymphoid
      Neoplasms and World Health Organization Classification, and staged according to
      the Ann Arbor classification. Stage I-II patients received radiochemotherapy
      predominant treatment, whereas stage III-IV patients received chemotherapy
      predominant treatment. RESULTS: Of the 89 cases, 60 (67%) were diffuse large B
      cell subtype, 11 (12%) were peripheral T-cell subtype, 5 (6%) were indolent
      lymphoma, 1 was anaplastic large T-cell lymphoma, and 1 was T lymphoblastic
      lymphoma; 81 (91%) were stage I-II disease. Of the 89 patients, 58 (72%) received
      radiochemotherapy, 19 (21%) received radiotherapy alone, 3 received chemotherapy
      alone, and 1 received radiochemotherapy combined with rituximab. The 5-year
      overall survival rate was 80%, that of stage I-II patients was 84%. Cox
      regression multivariate analysis showed that the survival rate was correlated to
      the value of international prognostic index (IPI), and whether the patient had
      primary refractory or relapsed disease, but was not correlated to sex, age,
      pathologic subtype, B symptoms, and bulky disease. CONCLUSIONS: Most patients
      with NHL of the tonsil are at early stages, with good prognosis. Diffuse large B
      cell lymphoma is the most common pathologic subtype. Primary refractory, relapse,
      and IPI>1 are independent prognostic factors.

PMID- 16613686
TI  - [Efficacy of rituximab-containing salvage regimens on relapsed or refractory B
      cell non-Hodgkin's lymphoma].
AB  - BACKGROUND & OBJECTIVE: The prognosis of relapsed or refractory B-cell lymphoma
      is poor, with a short-term survival after conventional second-line chemotherapy.
      Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like
      chemotherapy may improve both disease-freely survival and overall survival of
      naive patients, but it's role in the second-line treatment for relapsed non
      Hodgkin's lymphoma (NHL) is uncertain. This study was to evaluate the efficacy of
      rituximab-containing salvage regimens on relapsed or refractory NHL, and observe
      the toxicities. METHODS: Clinical data of 35 patients with relapsed or refractory
      NHL, treated in Cancer Center of Sun Yat-sen University, were analyzed
      retrospectively. Of the 35 patients, 19 were man, and 16 were women, with a
      median age of 53.5 years (ranged from 21 to 77); for ECOG performance status, 33
      (94.3%) scored 0-1; for international prognostic index (IPI), 20 (57.1%) scored 0
      1, 7 (20%) scored 2, 4 (11.4%) scored 3, and 4 (11.4%) scored 4-5; 23 cases of
      diffuse large B-cell lymphoma (DLBL) accounted for 65.7% among all subtypes.
      Rituximab (375 mg/m2) was administered intravenously at the day before each
      chemotherapy cycle. The second-or third-line salvage regimens included EPOCH,
      CHOP, DHAP, DICE, IVAC, IMVP-16, and FND. RESULTS: Of the 35 patients, 30
      received rituximab-combined regimens, and 5 received rituximab alone. A total of
      102 cycles of rituximab-containing salvage regimens were administered. The
      objective response rate of the 32 evaluable cases was 68.8%, with a complete
      remission (CR) rate of 40.6%; 3 patients achieved CR after radiotherapy following
      rituximab-based regimens, and 3 achieved CR after autologous hematopoietic stem
      cell transplantation. The most frequent adverse events were nausea, leukopenia,
      and alopecia. The addition of rituximab to chemotherapy only elevated the
      occurrence of mild infusion-related reactions, such as chills, fever, and
      pruritus. The median follow-up time was 12.5 months (ranged from 3 to 69 months);
      2 patients were lost, 10 were died (9 died of lymphoma, and 1 died of severe
      hepatitis), the other patients remained alive. The median progression-freely
      survival was 11.8 months (ranged from 3 to 33 months). The overall 1-, 2-, and 3
      year survival rates were 72.9%, 62.8%, and 62.8%, respectively. CONCLUSION:
      Rituximab-containing salvage regimens are effective and well tolerated, even in
      extensively pretreated patients with relapsed or refractory B-cell NHL.

PMID- 16613687
TI  - [Efficacy of rituximab-containing regimens on indolent B-cell lymphoma--a report
      of 34 cases].
AB  - BACKGROUND & OBJECTIVE: The efficacy of rituximab given alone or in combination
      with chemotherapy on naive or relapsed indolent lymphoma is good. This study was
      to investigate the efficacy and safety of rituximab-containing regimens for
      patients with indolent B-cell lymphoma in China. METHODS: From Mar. 1999 to Jan.
      2005, 34 patients with indolent B-cell lymphoma received rituximab-containing
      regimens with a median of 5 cycles (ranged from 3 to 8 cycles). Of the 34
      patients, 2 received rituximab alone, and 32 received rituximab-based regimens,
      which including CHOP (16 cases), FMD (5 cases), CHOPE (4 cases), EPOCH (2 cases),
      DICE (2 cases), DAHP (2 cases), and FN (1 case). RESULTS: Of the 34 patients, 30
      were evaluable for objective response. The overall response (OR) rate was 93.3%,
      and the complete response (CR) rate was 60.0%; the OR rate and CR rate of 22
      evaluable naive patients were 95.4% and 66.7%, those of 18 evaluable follicular
      lymphoma patients were 88.9% and 66.7%. With a median follow-up of 17 months (4
      68 months), the 1-year progression-freely survival rate was 85.3%.
      Myelosuppression was the major adverse event: 19 patients suffered from
      leukopenia with 4 cases of grade III-IV event, 5 suffered from thrombocytopenia
      with 4 cases of grade III-IV event, and 2 suffered from febrile neutropenia.
      Other adverse events included grade I-II nausea/vomiting, mild alopecia, and
      transient liver function abnormality. The infusional reaction of rituximab
      consisted of grade I-II rigor/febrile, skin rash, mild hypotension, and
      asymptomatic ventricular premature beat. CONCLUSION: Rituximab-containing
      chemotherapeutic regimens are effective for indolent B-cell lymphoma with mild
      toxicity.

PMID- 16613689
TI  - [Phase I clinical trial of intravenous recombinant human lymphotoxin-alpha
      derivative].
AB  - BACKGROUND & OBJECTIVE: Intravenous recombinant human lymphotoxin-alpha
      derivative (rhLTalpha-Da) is a novel biological antitumor reagent developed in
      China. This study was to evaluate the tolerance of tumor patients to rhLTalpha
      Da, confirm its maximum tolerable dose (MTD) in vivo, and to provide recommending
      dose for phase II trial. METHODS: The dose escalation of rhLTalpha-Da was as
      follows: 10 microg.(m2.day)-1, 20 microg.(m2.day)-1, and 33 microg.(m2.day)-.
      Each group contained at least 3 patients. rhLTalpha-Da was solved in 5% GS (100
      ml), and intravenously infused over 30 minutes daily for 5 consecutive days.
      RESULTS: A total of 24 patients were enrolled. Grade I-III chill and fever were
      the most common adverse events, with the occurrence rate of 79.2% (19/24). Other
      adverse events observed were dyspnea (3/24), nausea/vomiting (3/24), headache
      (4/24), fatigue (2/24), hypotension (2/24), and skin discomfort at irradiation
      region (2/24). No obvious abnormity of liver and renal functions was observed.
      The dose-limiting toxicities (DLT), which occurred at dose level of 33
      microg.(m2.day)-1, were grade III chill, grade III fever, and grade III dyspnea.
      Although there was no definite efficacy showed in this primary study, initial
      response to rhLTalpha-Da was seen on a minority of patients with cancers,
      including malignant melanoma, mycosis fungoides, and renal carcinoma.
      CONCLUSIONS: The MTD of rhLTalpha-Da is 33 microg.(m2.day)-1. The recommended
      dose for phase II clinical trial is 20 microg.(m2.day)-1.

PMID- 16613688
TI  - [Phase I clinical trail of intravenous pegylated recombinant human granulocyte
      colony-stimulating factor].
AB  - BACKGROUND & OBJECTIVE: Recombinant human granulocyte colony-stimulating factor
      (rhG-CSF) is effective in the prophylaxis and management of chemotherapy-induced
      neutropenia, but requires daily administration because of its short half-life.
      Pegylated rhG-CSF (PEG-rhG-CSF) is a long-acting reagent that permits less
      frequent injection. This study was to evaluate the safety and tolerance of PEG
      rhG-CSF in Chinese patients, and to explore its efficacy of enhancing absolute
      neutrophil count (ANC) and CD34+ cell count in peripheral blood. METHODS: Naive
      non-small lung cancer or breast cancer patients with normal bone marrow function
      were eligible for this open-labeled, dose-escalation trial. All patients received
      2 cycles of chemotherapy of identical regimen. In cycle 1, rhG-CSF (150
      microg/day) was administrated in case of febrile neutropenia or grade 4
      neutropenia; in cycle 2, patients received a single injection of PEG-rhG-CSF (30
      microg/kg, 60 microg/kg, 100 microg/kg, or 200 microg/kg) 48 h after
      administration of paclitaxel and carboplatin. RESULTS: All the 16 patients
      enrolled (4 in each dose group) were evaluable for safety and efficacy of PEG-rhG
      CSF. Main adverse events related to PEG-rhG-CSF were musculoskeletal pain or
      arthralgia (13/16), fatigue (10/16), dizziness (2/16), and injection-site pain
      (1/16). All adverse events were mild to moderate, and most of them were
      reversible without treatment. PEG-rhG-CSF enhanced ANC in a dose-dependent manner
      to some extent, and PEG-rhG-CSF at 60 microg/kg or higher doses prevented
      chemotherapy-induced neutropenia with sustained effect; CD34+ cells in peripheral
      blood were also increased. CONCLUSIONS: PEG-rhG-CSF is well tolerated, with no
      serious adverse event in this trial. The recommended dose of PEG-rhG-CSF for
      phase II trial is 100 microg/kg because of its adequate efficacy and less adverse
      events than those of 200 microg/kg.

PMID- 16613690
TI  - [Intrapericardial infusion of etoposide and cisplatin in treating malignant
      pericardial effusion of non-small cell lung cancer].
AB  - BACKGROUND & OBJECTIVE: Pericardiocentesis and intrapericardial infusion of
      chemotherapeutic drugs is the main treatment of malignant pericardial effusion.
      This study was to observe the efficacy and side effect of intrapericardial
      infusion of etoposide (VP-16) and cisplatin (DDP) on malignant pericardial
      effusion of non-small cell lung cancer (NSCLC). METHODS: Twenty-eight NSCLC
      patients with malignant pericardial effusion were treated with pericardiocentesis
      and intrapericardial infusion of VP-16 (200-300 mg) and DDP (80-100 mg).
      Intravenous chemotherapy were given 2 weeks after the pericardiocentesis.
      RESULTS: The overall response(OR) rate of the first-time treatment of the 28
      patients was 85.7%, with complete response (CR) rate of 71.4%; the OR rate of the
      second-time treatment was 100%. Only 4 patients needed second-time
      pericardiocentesis. Sixteen patients developed gastrointestinal tract reaction
      (mainly grade I-II), 12 developed myelosuppression (mainly grade I), and 1 showed
      mild abnormal of transaminase. For the 24 naive patients, the overall survival
      time was 14 months for stage IIIB and 10.9 months for stage IV; whereas for the 4
      patients with relapsed disease, the overall survival time was 6 months (from the
      time of relapse). CONCLUSION: Intrapericardial infusion of VP-16 and DDP is an
      effective treatment for malignant pericardial effusion of NSCLC.

PMID- 16613691
TI  - [Progress of medical and combined treatment for esophageal carcinoma].
AB  - The combined treatment for esophageal carcinoma evoked increasing attention in
      clinic. The combination of radiotherapy, chemotherapy and operation is the
      tendency of combined treatment for esophageal carcinoma. The rational and
      efficient combined treatment has made more satisfied curative effect than single
      treatment, which improved the patients' long-term survival rate. Using new
      chemotherapeutic agents, exploring neoadjuvant chemotherapy, and renewing
      knowledge of adjuvant chemotherapy are important developments on medical
      treatment for esophageal carcinoma. This review discussed the progress of medical
      and combined treatment for esophageal carcinoma from the aspects of curative
      effect, survival rate, adverse events, and so on.

PMID- 16613693
TI  - [Partial splenic embolization therapy for chronic idiopathic thrombocytopenic
      purpura in children: a report of 2 cases].

PMID- 16613692
TI  - [Farnesyl transferase inhibitors--a novel agent for breast cancer].
AB  - The ras family of proto-oncogenes are upstream mediators of several essential
      cellular signal transduction pathways involved in cell proliferation and
      survival. Point mutations of ras oncogenes result in constitutive activation of
      oncogenic Ras. The key step in post-translational processing of Ras protein is
      farnesylation by farnesyl transferase. Inhibitors of this enzyme were developed
      initially as a therapeutic strategy for Ras-mutated tumors. Moreover, it is now
      clear that farnesyl transferase inhibitors (FTIs) have activity independent of
      Ras, and show some effects on tumors without oncogenic ras mutations. Preclinical
      data show that FTIs can inhibit proliferation of breast cancer cells in vitro and
      in vivo, and phase II studies of FTI-R115777 in advanced breast cancer show
      encouraging results. Therefore, FTIs, used alone or with other agents, may be a
      novel therapeutic approach for breast cancer.

PMID- 16613694
TI  - [A case report of hydroa vacciniforme].

PMID- 16613695
TI  - Effect of human cytomegalovirus on proliferation of hematopoietic progenitor
      cells of cord blood.
AB  - OBJECTIVE: This study was designed to investigate the effect of human
      cytomegalovirus (HCMV) on the proliferation of colony forming unit granulocyte
      macrophage (CFU-GM), CFU-erythroid (CFU-E), burst forming unit-erythroid (BFU-E),
      CFU-multipotential (CFU-Mix) and CFU-megakaryocytic (CFU-Mk) progenitor cells of
      cord blood in vitro as well as the possible mechanism. METHODS: Twenty cord blood
      specimens were collected from the umbilical vein of normal full-term neonates
      delivered spontaneously. This study consisted of five groups: 3 Infection groups
      in which 0.1 mL 10(3), 10(4) and 10(5) plague forming unit (PFU) HCMV-AD169 virus
      solution was added to the culture system, an Inactivated control group in which
      the equal volume of inactivated virus solution was added, and a Blank control
      group (normal progenitor cells culture system without HCMV virus infection).
      Colony forming unit-assay was applied to detect the effects of HCMV-AD169 strain
      on the colony formation, inhibition rate and colony-maintaining duration of CFU-
      GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk of cord blood. PCR technique was used to
      demonstrate the existence of HCMV-DNA in the colony cells of cultured CFU-GM, CFU
      E, CFU-Mix and CFU-Mk. RESULTS: HCMV-AD169 (10(3)PFU) in low concentration had
      inhibition effects on colony formation of the CFU-Mix and CFU-Mk (P < 0.05),
      whereas 10(5) PFU and 10(4) PFU HCMV-AD169 lead to decreased colonies in CFU-GM,
      CFU-E, BFU-E, CFU-Mix and CFU-Mk compared with the Blank control and the
      Inactivated control groups (P < 0.05). The suppression effect of HCMV on the
      colony formation was dose-dependent. The colony-maintaining duration of the CFU
      GM, CFU-E, BFU-E, CFU-Mix and CFU-Mk in the 10(5) PFU and 10(4) PFU HCMV
      infection groups was significantly shorter than that in the two control groups (P
      < 0.01). The low concentration of HCMV-AD169 (10(3)PFU) infection resulted in a
      shortened colony-maintaining duration of the CFU-Mix and CFU-Mk (P < 0.01), but
      had no effects on the colony-maintaining duration of CFU-GM, CFU-E and BFU-E. PCR
      amplification demonstrated the existence of HCMV-AD169 DNA in the colony cells of
      the three Infection groups. CONCLUSIONS: HCMV-AD169 strain can infect
      hematopoietic progenitors of cord blood and inhibit the proliferation of
      hematopoietic progenitors, associated with anemia, neutropenia and
      thrombocytopenia in HCMV patients.

PMID- 16613696
TI  - [Plasma levels of adrenomedullin in children with congenital heart disease].
AB  - OBJECTIVE: This study was designed to investigate the pathophysiological role of
      adrenomedullin (ADM) in congenital heart disease. METHODS: Forty-eight children
      with congenital heart disease confirmed by cardiac echocardiography and
      catheterization were studied. The patients were divided into three groups on the
      basis of hemodynamic indices measured during cardiac catheterization: high
      pulmonary blood flow with (group 1) or without (group 2) pulmonary hypertension
      (mean pulmonary arterial pressure > 20 mmHg) and a cyanosis group (without high
      pulmonary blood flow) (group 3). Six children who recovered from Kawasaki disease
      were used as a Control group. Plasma ADM levels were measured by
      radioimmunoassay. RESULTS: The plasma ADM levels from the femoral vein were
      significantly higher than those from femoral artery in patients with congenital
      heart disease. The patients from group 1 and group 3 had higher plasma ADM levels
      (1.9 +/- 1.8 pmol/L and 2.4 +/- 1.3 pmol/L, respectively) than the controls (1.0
      +/- 1.4 pmol/L; P < 0.01). Plasma ADM levels were significantly negatively
      correlated with mean systemic arterial pressure, oxygen saturation in mixed vein
      and oxygen saturation in systemic artery (r=-0.401, -0.562, -0.600, respectively;
      P < 0.01) but positively correlated with pulmonary vascular resistance (r=0.406;
      P < 0.01). CONCLUSIONS: Plasma ADM levels are increased in congenital heart
      disease with high pulmonary blood flow and hypertension or with cyanosis. Plasma
      ADM levels are related to pulmonary arterial resistance and hypoxemia. Increased
      ADM levels may play roles in reducing the pulmonary arterial resistance and
      alleviating hypoxemia in these patients.

PMID- 16613697
TI  - [Long-term effect of high dose chemotherapy combined with stem cell
      transplantation on stage IV neuroblastoma in children].
AB  - OBJECTIVE: Neuroblastoma is a highly malignant tumor. Stage IV neuroblastoma has
      a very poor long-term outcome by conventional chemotherapy and surgery and better
      therapies are essential. This study aimed to explore the long-term effect of high
      dose induction chemotherapy combined with autologous peripheral blood stem cell
      transplantation and 13-cis retinoid acid treatment on stage IV neuroblastoma in
      children. METHODS: Twenty-eight children with stage IV neuroblastoma, aged 2.1
      11.5 years (mean 3.3 +/- 1.9 years), were employed for the study. Primary sites
      of the tumors included adrenal (n=23), chest (n=3), chest-abdomen (n=1) and
      sacrum (n=1). Before autologous peripheral blood stem cell transplantation the
      patients received 6 courses of intensive induction chemotherapy. During
      chemotherapy the autologous peripheral blood stem cells were harvested and the
      tumor excision was done. After transplantation the local radiation and 13-cis
      retinoid acid therapy were administered. RESULTS: After 6 courses of induction
      chemotherapy 13 patients got complete remission (CR), 11 got partial remission
      (PR), and 4 had no response. The 24 patients who received CR or PR completed the
      full therapy. A 3.5 +/- 0.7 years follow-up showed that the 4-year event-free
      survival of the CR and PR patients was 29.2%. The median no-relapse survival time
      in CR patients was 4.1 +/- 0.7 years but 2.8 +/- 0.5 years in PR patients (t=
      3.9, P < 0.01). CONCLUSIONS: High dose chemotherapy combined with autologous
      peripheral stem cell transplantation and 13 cis-retinoid acid treatment can
      improve the long-term outcome of patients with stage IV neuroblastoma. The
      patients in CR before transplantation had better outcomes than those in PR.

PMID- 16613698
TI  - [Induction of apoptosis and inhibition of HL-60 cell proliferation by survivin
      antisense oligonucleotide].
AB  - OBJECTIVE: To investigate the effects of survivin antisense oligonucleotide (ODN)
      on cell proliferation and apoptosis of HL-60 cells. METHODS: Synthetic ODN was
      completely phosphorothioate-modified. Cationic lipid-mediated antisense ODN was
      transferred into HL-60 cells. The expression of survivin mRNA and protein was
      detected by RT-PCR and Western Blot. The incorporation of MTT was used as the
      measurement of HL-60 proliferation. The cell-cycle and apoptosis were analyzed by
      flow cytometry. RESULTS: HL-60 cells spontaneously expressed survivin mRNA and
      protein. Both mRNA and protein expression of survivin decreased significantly in
      the antisense ODN transfected cells in comparison to that in the original cells
      and cells transfected with sense ODN. Survivin antisense ODN significantly
      inhibited cell proliferation and induced apoptosis in a dose-dependent manner.
      The cell-cycle in the antisense ODN-transfected cells stopped at the G2/M phase.
      CONCLUSIONS: Antisense ODN targeting at survivin mRNA can inhibit HL-60 cell
      proliferation and induce G2/M stop and apoptosis.

PMID- 16613699
TI  - [Expression of survivin and its location in bone marrow cells of childhood acute
      leukemia: relationship to therapeutic efficacy].
AB  - OBJECTIVE: Survivin, a unique member of the inhibitor of apoptosis protein (IAP)
      family, plays an important role in regulating both apoptosis and cell division.
      Overexpression of survivin is associated with increased risk of recurrence and
      poor outcome in cancer patients. This study aimed to investigate the expression
      of survivin and its location as well as the relationship between cellular
      location and expression of survivin and the therapeutic efficacy at the cellular
      level. METHODS: The expression of survivin protein was detected by
      immunohistochemical assay in bone marrow cells from 62 children with acute
      leukemia and 40 hospitalized children who did not have leukemia (Control group),
      and in a human acute T lymphocytic leukemia cell line (Molt-4 cells) treated in
      vitro with daunorubicin (DNR). Cell apoptosis was detected using flow cytometry.
      RESULTS: Survivin protein was expressed in 41.9% of the 62 children with acute
      leukemia but in only 5.0% of the Control group (chi(2)=16.66; P < 0.01). The
      expression rate of survivin was 46.2% in cytoplasm and 53.9% in nucleus in the
      children with acute leukemia (chi(2)0.3077; P> 0.05). However, the remission rate
      of patients in whom survivin expression was seen in the nucleus was significantly
      higher than that in patients in whom survivin was expressed in cytoplasm after
      chemotherapy. The survivin expression in Molt-4 cells decreased remarkably by DNR
      treatment in a time and dosage-dependent manner. DNR treatment also induced
      survivin transllocation from cytoplasm to nucleus and cell apoptosis in a time
      and dosage-dependent manner. CONCLUSIONS: Survivin may play an important role in
      the development and prognosis of childhood acute leukemia. The different
      expression pattern of survivin in the cytoplasm and the nucleus may be associated
      with therapeutic efficacy and prognosis in acute leukemia. DNR may reduce the
      survivin expression in leukemic cells and induce cell apoptosis.

PMID- 16613700
TI  - [Differential response of developing human fetal lung explants to hyperoxia and
      the effects of dexamethasone on hyperoxia-exposed lungs].
AB  - OBJECTIVE: This study aimed to explore the effects of hyperoxia on the
      development of fetal lung by investigating the changes of morphological and cell
      proliferation induced by hyperoxia in cultured fetal lungs as well as the effects
      of dexamethasone on hyperoxia-exposed lungs. METHODS: Human fetal lung explants
      at the pseudoglandular stage of development were cultured randomly either in
      normoxia (21% O2/5% CO2) or hyperoxia (95% O2/5% CO2) for 72 hrs. Dexamethasone
      was added into the feeding medium at the concentration of 10(-6)M. Harvested
      tissues were stained for pancytokeratin to identify epithelial cells, with Ki-67
      as a marker of proliferation. The effects of lung morphometry were analyzed using
      computer assisted image analysis. The mean airway thickness, the proportion of
      the surface area occupied by airways, the mean airway surface area and the index
      of the epithelium proliferation were measured. RESULTS: The lung architectures
      remained unchanged after 72 hrs normoxia culture, whereas hyperoxia culture
      resulted in significant dilation of airways and thinning of epithelium, with the
      surface area of airways of 6662 microm(2) vs 2728 microm(2) and the thickness of
      airways of 7.8 microm vs 8.1 microm (P < 0.05). Hyperoxia culture also resulted
      in an increase in the proportion of the surface area occupied by airways than
      normoxia culture (35.2% vs 23.4%; P < 0.05). The surface area of airways (3174
      microm(2)) and the proportion of the surface area occupied by airways (23.9%)
      decreased significantly in hyperoxia-cultured lungs after dexamethasone
      administration (P < 0.05). The epithelium proliferation index in hyperoxia
      cultured lungs (21.8%) was higher than that in normoxia-cultured lungs (5.1%) and
      dexamethasone-treated hyperoxia-cultured lungs (7.4%) (P < 0.05). CONCLUSIONS:
      The exposure of pseudoglandular lungs to hyperoxia modulates the lung
      architecture to resemble saccular lungs with higher epithelium proliferation
      index. Dexamethasone may inhibit the effects induced by hyperoxia.

PMID- 16613701
TI  - [Association of Q576R polymorphism in the interleukin-4 receptor gene with serum
      IgE levels in children with asthma].
AB  - OBJECTIVE: Interleukin-4 plays a key role in the development of asthma. Overseas
      studies have shown that Q576R polymorphism in the interleukin-4 receptor (IL-4R)
      gene is related to asthma as well as increased serum IgE levels. This study was
      designed to investigate the association of Q576R polymorphism in IL-4R gene with
      childhood asthma and serum IgE levels. METHODS: The polymorphism of IL-4R Q576R
      was determined by PCR/RFLP and serum total IgE level was measured using ELISA in
      94 children with asthma. Sixty-eight healthy children served as controls.
      RESULTS: The distribution frequency of heterozygous genotype Q576R (41%) and
      mutant allele R576 (26%) was significantly higher in children with asthma than
      that of controls (16% each) (P < 0.01; P < 0.05). The total serum IgE level
      between patients with genotype Q576R and Q576Q was not significantly different
      (225.78 +/- 51.43 IU/mL vs 163.24 +/- 31.32 IU/mL, P> 0.05). CONCLUSIONS: The
      mutant R576 allele of IL-4R may be one of the candidate genes for susceptibility
      to asthma. Allele R576 of IL-4R is related to asthma but is irrelevant to the
      total serum IgE level in children with asthma.

PMID- 16613703
TI  - [Bacterial pathogens and resistance patterns in community acquired pediatric
      urinary tract infection: experience of 152 cases].
AB  - OBJECTIVE: This study investigated the pathogen distribution and resistance
      patterns in childhood urinary tract infection in order to provide references for
      optimal use of antibiotics in the treatment of this disorder. METHODS: The
      clinical data of 152 children with community acquired urinary tract infection
      (urinary culture positive) between December 2001 and December 2004 were studied
      retrospectively. The bacterial pathogens of urinary tract infection and
      antimicrobial resistance were analyzed. RESULTS: Gram-negative bacilli was
      predominant pathogenic bacteria, accounting for 79.0% of the cases, and
      Escherichia coli (E. coli) was most commonly found (56.2%). Gram-positive cocci
      accounted for 18.4%, including 15.1% of Enterococcus faecalis. Fungi was rarely
      seen, accounting for only 2.6%. E. coli had a resistance rate of more than 50% to
      ampicillin, amoxicillin/clavulate, co-trimoxazole, cefradine, and fosomycin, but
      a very low resistance rate (< 4%) to 3rd generation cefalosporin, nitrofurantoi,
      azactom and amikacin. Enterococcus faecalis had a low resistance rate (< 20%) to
      ampicillin, vancomycin, penicillin, and nitrofurantoin. CONCLUSIONS: E. coli is
      the major pathogen in community acquired pediatric urinary tract infection, and
      Enterococcus has been become another important pathogen. Selection of antibiotics
      for the treatment of this disorder should base on drug-sensitive test results.

PMID- 16613702
TI  - [Evaluation of association between an acute attack of childhood bronchial asthma
      and Chlamydia pneumoniae infection].
AB  - OBJECTIVE: To identify whether there is an association between an acute attack of
      childhood bronchial asthma and Chlamydia pneumoniae (CP) infection. METHODS:
      Serum specific antibodies IgM and IgG to CP were detected by ELISA in 120
      asthmatic children with an acute attack and 82 healthy children. RESULTS: Anti-CP
      IgM was demonstrated in 22 cases (18.3%) and anti-CP IgG was demonstrated in 32
      cases (26.7%) out of the 120 asthmatic patients. The incidence of CP infection in
      asthmatic children was significantly higher than that in healthy controls (3.7%)
      (P < 0.01). Glucocorticoid inhalation treatment alone resulted in a remission of
      an acute attack of asthma in 15 cases out of the 32 cases with CP infection, but
      17 cases required glucocorticoid inhalation treatment together with anti-CP
      infection treatment (macrolide antibiotics, eg. azithromycin) for remission of
      asthma attack. CONCLUSIONS: There may be a link between an acute attack of
      childhood asthma and CP infection. It is thus necessary to detect the CP-specific
      antibodies in asthmatic children for proper treatment.

PMID- 16613704
TI  - [Levels of atrial natriuretic peptide in umbilical cord blood of high risk
      neonates].
AB  - OBJECTIVE: Atrial natriuretic peptide (ANP) is a cardiac hormone with many
      biological effects. Hypersecretion may lead to hyponatremia. This study examined
      the umbilical ANP levels in high risk neonates. METHODS: A total of 117 high risk
      neonates born between June, 2004 and June, 2005 were divided into Simple asphyxia
      and Normal score groups according to their Apgar's scores. The Simple asphyxia
      group was subdivided into Mild (n=20) and Severe asphyxia groups (n=17), and the
      Normal score group was subdivided into Infection (n=25) and Non-infection groups
      (n=55). Forty normal neonates were used as the Control group. The samples of
      umbilical cord blood were collected at delivery and the umbilical ANP levels were
      measured by radioimmunoassay. Meanwhile the sodium levels in the peripheral vein
      were measured. RESULTS: The mean umbilical ANP levels in high risk neonates were
      significantly higher than those in the normal neonates. A more significant
      increase of the umbilical ANP level was observed in premature infants (1.46 +/-
      0.39 ng/mL), and neonates with serious infection (1.16 +/- 0.35 ng/mL) and with
      severe asphyxia (2.12 +/- 0.46 ng/mL) compared with the normal neonates (0.62 +/-
      0.33 ng/mL; P < 0.01). The serum sodium level was negatively correlated with the
      umbilical ANP level (r=-0.99, P < 0.01). CONCLUSIONS: The umbilical ANP levels
      increased significantly in the high risk neonates, suggesting high risk neonates
      are susceptible to hyponatremia.

PMID- 16613705
TI  - [Association between vitamin D receptor gene polymorphism and vitamin D
      deficiency rickets].
AB  - OBJECTIVE: To explore the genetic susceptibility of children to vitamin D
      deficiency rickets through studying the association between Vitamin D receptor
      (VDR) gene polymorphism and vitamin D deficiency rickets. METHODS: One hundred
      and fifty-nine children (100 boys and 59 girls, aged 0 to 2 years), with new
      onset vitamin D deficiency rickets were enrolled. The patients sampled from a
      community of Jiamusi City, Heilongjiang Province. Seventy-eight healthy age
      matched children (46 boys and 32 girls) were used as the controls. VDR gene
      polymorphism (cleaved by restriction endonuclease Fok I) was analyzed by
      polymerase chase reaction-restriction fragment length polymorphism (PCR-RFLP).
      The frequencies of the VDR genotype and allele were compared between the two
      groups. RESULTS: The frequencies of FF, Ff and ff genotypes were 37%, 51% and 12%
      in the Rickets group, and 18%, 55% and 27% in the Control group. A significant
      difference was found in the frequency distribution of the VDR genotype between
      the two groups (chi(2)(0.01(2))=9.210, chi(2)=13.3880, P < 0.01). In the Rickets
      group, f allele frequency was lower (37% vs 54%), while the F allele was more
      common than the Control group (63% vs 46%). CONCLUSIONS: There is an association
      between the VDR gene Fok I polymorphism and vitamin D deficiency rickets. The
      individuals with the F allele are more susceptible to vitamin D deficiency
      rickets.

PMID- 16613706
TI  - [A difficult and complicated case study: neonatal intrahepatic cholestasis caused
      by citrin deficiency].
AB  - Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a kind
      of inborn errors of metabolism, with the main clinic manifestations of jaundice,
      hepatomegaly, and abnormal liver function indices. As a mitochondrial solute
      carrier protein, citrin plays important roles in aerobic glycolysis,
      gluconeogenesis, urea cycle, and protein and nucleotide syntheses. Therefore
      citrin deficiency causes various and complicated metabolic disturbances, such as
      hypoglycemia, hyperlactic acidemia, hyperammonemia, hypoproteinemia,
      hyperlipidemia, and galactosemia. This paper reported a case of NICCD confirmed
      by mutation analysis of SLC25A13, the gene encoding citrin. The baby (male, 6
      months old) was referred to the First Affiliated Hospital with the complaint of
      jaundice of the skin and sclera, which it had suffered from for nearly 6 months.
      Physical examination showed obvious jaundice and a palpable liver 5 cm below the
      right subcostal margin. Liver function tests revealed elevated enzymatic
      activities, like GGT, ALP, AST, and ALT, together with increased levels of TBA,
      bilirubin (especially conjugated bilirubin), and decreased levels of total
      protein/albumin and fibrinogen. Blood levels of ammonia, lactate, cholesterol,
      and triglyceride were also increased, and in particular, the serum AFP level
      reached 319,225.70 microg/L, a extremely elevated value that has rarely been
      found in practice before. Tandem mass analysis of a dried blood sample revealed
      increased levels of free fatty acids and tyrosine, methionine, citrulline, and
      threonine as well. UP-GC-MS analysis of the urine sample showed elevated
      galactose and galactitol. The baby was thus diagnosed with suspected NICCD based
      on the findings. It was then treated with oral arginine and multiple vitamins
      (including fat-soluble vitamins A, D, E, and K), and was fed with lactose-free
      and medium-chain fatty acids enriched formula instead of breast feeding. After
      half a month of treatment, the jaundice disappeared, and the laboratory findings,
      including liver function indices, blood levels of ammonia, lactate and AFP, were
      returned to normal level. The baby was followed up for 6 months. It developed
      well, and the abnormal laboratory findings, including MS-MS and UP-GC-MS analysis
      results, have been corrected, except a slightly elevated lactate level sometimes.
      SLC25A13 gene mutation analysis for the patient revealed a compound heterozygote
      of mutation 851del4 and 1638ins23 and therefore NICCD was definitely diagnosed.

PMID- 16613707
TI  - [Effects of different oxygen inhalation modes on retinal vessels development in
      neonatal mice].
AB  - OBJECTIVE: This study was designed to investigate the effects of different oxygen
      inhalation modes on retinal vessels development in neonatal mice in order to
      provide experimental data for proper oxygen therapy for premature infants.
      METHODS: A total of 144 postnatal day (P) 7 C57BL/6J mice were randomly assigned
      into 6 groups according to different oxygen inhalation modes (n=24). Experimental
      group 1 was exposed to 30%, 40%, 50%, 60% and 75% oxygen in turn for one day
      respectively, followed by room air exposure for 5 days. Experimental group 2 was
      exposed to 75%, 60%, 50%, 40% and 30% oxygen in turn for one day respectively,
      followed by room air exposure for 5 days. Experimental group 3 was exposed to 75%
      oxygen for 5 days, followed by room air exposure for 5 days. Experimental group 4
      was exposed to 75% oxygen for 5 days, 50% oxygen for 2 days and 30% oxygen for 2
      days, then room air exposure for 6 days. The supplemental 75% oxygen and room air
      recovering was performed alternately for the mice in Experimental group 5 for 3
      times and then room air exposure for 5 days. The Control group was exposed to
      room air for consecutive 10 days. The retinal vascular development and
      proliferation were evaluated by the retinal flat-mounts (ADPase stained retina)
      and cross-section. RESULTS: The peripheral vascular pattern was clear, and a few
      avascular areas were seen in the Control group at P12. At P14 the avascular area
      disappeared. At P17, the entire vascular pattern became completely normal. In the
      Experimental groups 1, 3 and 5, the central vessels became tortuous and
      constricted and the central avascular area increased at P12. At P14,
      neovascularization was seen peaking at P17 in the Experimental groups 1, 3 and 5.
      In the Experimental group 4, the central avascular area increased and
      neovascularization was seen at P14, but the central avascular area was reduced
      and abnormal neovascularization disappeared, with slight constriction of the deep
      vessels, at P17. Five days later the vascular pattern became almost normal in the
      Experimental group 4. The retinal vascular form of the Experimental group 2 was
      similar to that of the Control group. The average number of neovascular nuclei
      extending into the vitreous per cross-section in the Experimental groups 1, 2, 3,
      4, and 5 and the Control group was 49.50 +/- 1.36, 5.17 +/- 0.67, 47.68 +/- 4.70,
      5.74 +/- 2.37, 29.15 +/- 2.48, and 1.22 +/- 0.20 respectively. There were
      significant differences between the Experimental groups 1, 3, 5 and the Control
      group (P < 0.05). CONCLUSIONS: The effects of different oxygen inhalation modes
      on the retinal vessels development in neonatal mice were different. The obvious
      fluctuation of inhaled oxygen concentration and abrupt stop of supplemental
      oxygen after high levels of supplemental oxygen may severely affect the
      development of retina vascular, leading to the pathologic changes similar to
      retinopathy of prematurity.

PMID- 16613708
TI  - [Role of caspase-1 and cytokines activated by caspase-1 in brain injury of the
      developing rats following recurrent seizures].
AB  - OBJECTIVE: The expressions of caspase-1 and cytokines activated by caspase-1 are
      associated with the pathophysiology of many diseases for its proinflammatory and
      proapototic peculiarity. However its relationship to brain injury of developing
      rats following recurrent seizures has not yet been identified. This study aimed
      to investigate the role of caspase-1 and cytokines activated by caspase-1 in
      brain injury of developing rats following recurrent seizures. METHODS: A total of
      96 postnatal 20 day Sprague-Dawley rats were randomly assigned into Control and
      Seizure groups. Seizures were induced in the Seizure group by flurothyl
      inhalation daily for six days. Brain tissues were sampled at 6 hrs, and at 1, 3,
      and 7 days after last seizure. The expressions of caspase-1, interleukin (IL)-18
      and IL-1beta mRNA in the cerebral cortex were detected by RT-PCR. The water
      content of the brain and the pathological changes of cortex nerve cells were
      observed. Brain injury was evaluated using a semiquantitative neuropathological
      scoring system. RESULTS: The levels of caspase-1 and IL-18 mRNA in the cerebral
      cortex of the Seizure group were obviously higher than those in the Control group
      at 6 hrs, and at 1, 3, and 7 days after seizure (P < 0.05 or P < 0.01). The
      expression of IL-1beta mRNA in the Seizure group exhibited a biphasic pattern:
      increased significantly at 6 hrs, and at 1 and 7 days post-seizure (P < 0.01),
      but was not significantly different from the Control group at 3 days post
      seizure. Edema, degeneration and necrosis of nerve cells in cerebral cortex,
      accompanying by inflammatory cell infiltration and apoptosis of nerve cells, were
      observed under a light microscope in the Seizure group after recurrent seizures.
      The water content of the brain in the Seizure group increased significantly
      compared with that in the Control group at 6 hrs, and at 1 and 3 days after
      recurrent seizures (P < 0.01). The Seizure group had significantly higher
      neuropathological scores than the Control group at each time point (P < 0.01).
      CONCLUSIONS: Caspase-1 and cytokines activated by caspase-1 play an important
      role in the developing brain injury after recurrent seizures.

PMID- 16613709
TI  - [Expression of p53 in neonatal mice following hypoxia-ischemia and effects of its
      inhibitor on neonatal brain injury].
AB  - OBJECTIVE: p53-induced apoptosis is crucial in the development of hypoxic
      ischemia (HI) brain damage and neurodegenerative disorders. Some experimental
      research has shown that a synthetic inhibitor of p53 can protect neurons against
      apoptosis. This study aimed to explore the expression of p53 in neonatal mice
      following HI brain damage and the effect of p53 inhibitor (pifithrin-alpha, PFT
      alpha) on brain damage. METHODS: HI was induced in 9-day-old mice pups by
      ligation of left carotid artery and 10% oxygen exposure for 55 minutes. The pups
      were sacrificed and the brains were taken out at 3, 8, 24, and 72 hrs post-HI.
      The brains were sectioned and stained with antibody against p53 and microtubule
      associated protein 2 (MAP-2). PFT-alpha was injected intraperitoneally: in
      experiment 1, immediately after HI with different dosages (1, 2 and 8 mg/kg); in
      experiment 2, 2 mg/kg at different HI times (1 hr before HI, and immediately and
      1 hr after HI). Control animals without HI received injections of 0.5% dimethyl
      sulfoxide. Brain damage was evaluated by gross morphology scoring at 72 hrs after
      HI. RESULTS: The number of p53 positive cells in the cortex, hippocampus and
      striatum of the ipsilateral hemisphere increased significantly and peaked at 3-8
      hrs post-HI when compared with those of contralateral hemisphere as well as
      normal controls. The positive cells distributed mainly in the MAP-2 negative
      area. Both different dosages and different injection time PFT-alpha treatment did
      not reduce the extent of brain damage. CONCLUSIONS: The immunoactivity of p53
      increased significantly as early as 3 hrs post-HI. The distribution area of p53
      expression was consistent with that of brain damage. The p53 inhibitor PFT-alpha
      has no protective effects against HI brain damage in neonatal mice.

PMID- 16613710
TI  - [Gamma-aminobutyric acid B receptor regulates the expression of hydrogen
      sulfide/cystathionine-beta-synthase system in recurrent febrile seizures].
AB  - OBJECTIVE: Febrile seizure (FS) is one of the most common seizure types in
      children. Our previous studies have demonstrated that both gamma-aminobutyric
      acid B receptor (GABABR) and hydrogen sulfide (H2S) are involved in the
      pathogenesis of FS. This study was designed to explore the effect of GABABR on
      H2S/cystathionine-beta-synthase (CBS) system in recurrent FS. METHODS: Sixty-four
      Sprague-Dawley rats aged 21 days were randomly assigned into four groups: Control
      (37 degrees C water bath exposure), FS, FS+baclofen (GABABR excitomotor), and
      FS+phaclofen (GABABR inhibitor) groups (n=16 each). FS was induced by warm water
      bath exposure (45.2 degrees C, once every 2 days, 10 times in total. The plasma
      level of H2S was detected by the spectrophotometer. The expression of CBS mRNA
      was examined by in situ hybridization. The expressions of CBS protein was
      observed by immunohistochemistry. RESULTS: The plasma level of H2S increased in
      the FS+baclofen group (427.45 +/- 15.91 micromol/L) but decreased in the
      FS+phaclofen group (189.72 +/- 21.53 micromol/L) compared with that in the FS
      group (362.14 +/- 19.71 micromol/L). The expressions of CBS mRNA and protein were
      up-regulated in the FS+baclofen group but were down-regulated in the FS+phaclofen
      group compared with those in the FS group. CONCLUSIONS: GABABR modulated the
      expression of H2S/CBS system in recurrent FS.

PMID- 16613711
TI  - [Transdifferentiation and collagen-synthesis effects of exogenous connective
      tissue growth factor on renal tubular epithelial cells in vitro].
AB  - OBJECTIVE: To investigate the effects of recombinal human connective tissue
      growth factor (rhCTGF) stimulation on epithelial-myofibroblast
      transdifferentiation (EMT) and collagen-synthesis in human renal tubular
      epithelial cell line (HK2) in vitro. METHODS: The cultured HK2 cells were
      stimulated with rhCTGF of 5 ng/mL. The morphological changes were observed under
      an inverted microscope. The cells were collected at 0, 3, 6, 12, 24 and 48 hrs
      after rhCTGF stimulation. The expression of E-cadherin,alpha-smooth muscle actin
      (alpha-SMA), collagen Ialpha1 (Col Ialpha1) and collagen IValpha1 (Col IValpha1)
      mRNAs were detected by RT-PCR. RESULTS: rhCTGF stimulation changed the HK2 cell
      appearance from oval to fusiformdown-regulated the E-cadherin mRNA expression and
      up-regulated alpha-SMA mRNA expression, but had no effects the Col Ialpha1 and
      Col IValpha1 mRNA expression. CONCLUSIONS: Exogenous CTGF can mediate the EMT but
      has no collagen-synthesis effects on HK2 cells.

PMID- 16613712
TI  - [Relationship between expression of aquaporin-1, -5 and pulmonary edema in
      hyperoxia-induced lung injury in newborn rats].
AB  - OBJECTIVE: Aquaporin (AQP) is a group of cell membrane transporting proteins. The
      study was designed to investigate the changes of AQP1 and AQP5 in the lung tissue
      under hyperoxia and their roles in pulmonary edema. METHODS: Two hundred newborn
      rats were randomized into different oxygen concentrations exposure: FiO2=0.80
      (Experimental group 1), FiO2=0.60 (Experimental group 2), FiO2=0.40 (Experimental
      group 3) and FiO2=0.21 (Air control group). Rats were sacrificed at 1, 3, 5, 7
      and 14 days after the beginning of experiment (10 rats each time point). The
      expressions of AQP1 and AQP5 were examined by Western Blot. The ratio of lung wet
      weight to lung dry weight (wet-to-dry weight ratio, W/D), and the protein content
      in bronchoalveolar lavage fluid (BALF) were measured. RESULTS: Compared with the
      Air control group, the W/D ratio and the protein content in BALF in the three
      experiment groups increased significantly and the increased extent was positively
      related to the duration and the oxygen concentration of hyperoxia-exposure. The
      expression of AQP1 in the experimental groups began to decrease at the 3rd day
      and significant differences were found at the 5th and the 7th days after
      hyperoxia-exposure compared with that in the Air control group (P < 0.05). The
      AQP1 expression was restored somewhat at the 14th day after hyperoxia-exposure,
      but it was still lower in the Experimental groups 1 and 2 than that in the Air
      control group (P < 0.05). The expression of AQP5 in the experimental groups were
      reduced compared with that in the Air control group 3 days after hyperoxia
      exposure and the decrease of AQP5 expression was associated with duration of
      hyperoxia-exposure. The comparison among three experimental groups showed that
      the decrease of AQP1 and AQP5 expressions was associated with the concentration
      of hyperoxia-exposure. CONCLUSIONS: The expressions of AQP1 and AQP5 decreased in
      hyperoxia-induced lung injury and correlated with the severity of pulmonary
      edema.

PMID- 16613714
TI  - [Inhaled nitric oxide for newborn infants with severe respiratory failure].

PMID- 16613713
TI  - [Effect of glucocorticoid on the expression of Puma in acute lymphoblastic
      leukemia].
AB  - OBJECTIVE: Glucocorticoid can induce apoptosis by regulating some genes'
      expression, but its effect on the pro-apoptotic protein Puma in leukemia remains
      unclear. This study was designed to investigate the effect of glucocorticoid on
      the expression of Puma in glucocorticoid-induced apoptosis of acute lymphoblastic
      leukemia cells in vitro. METHODS: Leukemia cells from acute lymphoblastic
      leukemia patients were transplanted into the immunodeficient mice. The
      transplanted leukemia cells were collected and then were treated with
      dexamethasone at the final concentration of 1 microM. The expression of Puma
      protein and mRNA in leukemia cells after dexamethasone treatment was detected by
      Western Blot and real-time quantitative PCR. A drug sensitive test was performed
      by MTT assay. RESULTS: The leukemia cells which came from the patients who had
      good clinical outcomes were sensitive to dexamethasone, while the ones from the
      patients who had poor clinical outcomes were resistant to dexamethasone in vitro.
      The sensitivity to dexamethasone in vitro between the resistant and sensitive
      leukemia cells was significantly different (P < 0.05). No upregulation of Puma
      protein and mRNA was detected in resistant and sensitive leukemia cells after
      dexamethasone treatment. CONCLUSIONS: Glucocorticoid can not upregulate the
      expression of Puma in glucocorticoid-induced apoptosis of acute lymphoblastic
      leukemia cells in vitro.

PMID- 16613715
TI  - [Temperament characteristics of children with cardiac neurosis].

PMID- 16613716
TI  - [Antiepileptic drug hypersensitivity syndrome: a report of 6 cases].

PMID- 16613717
TI  - [Value of the P/PR segment ratio in the evaluation of the left cardiac function
      of children with rheumatic heart disease].

PMID- 16613718
TI  - [Interstitial cells of Cajal and gastrointestinal diseases].

PMID- 16613719
TI  - [Essential fatty acid and immune responses].

PMID- 16613720
TI  - [A case report of spinal muscular atrophy].

PMID- 16613721
TI  - Sample preparation and RPHPLC determination of diuretics in human body fluids.
AB  - This article describes reverse phase high-performance liquid chromatography
      (RPHPLC) methods for determination of diuretics in different human body fluids
      (whole blood, plasma, serum or urine). Sample preparation procedures, including
      solid-phase extraction, liquid-liquid extraction, dilution, precipitation as well
      as automated RPHPLC procedures, are discussed in order to present the advantages
      and disadvantages of each type of sample preparation. Also, values of analytical
      recovery of each procedure used for sample preparation are summarized. The most
      important RPHPLC parameters (detection mode, stationary phase, mobile phase,
      sensitivity, etc.) are also summarized and discussed.

PMID- 16613722
TI  - Enhanced delivery of etoposide to Dalton's lymphoma in mice through polysorbate
      20 micelles.
AB  - The study evaluates the possibility of enhancing uptake of etoposide
      (topoisomerase II inhibitor) by tumor when delivered through polysorbate 20
      micelles. The micelle formation was ascertained by determining the critical
      micellar concentration (CMC) with a du Nouy ring tensiometer and by size
      measurement using dynamic light scattering. Addition of 5% ethanol decreased the
      CMC of Polysorbate 20 (from 5.0 x 10(-5) to 4.54 x 10(-5) mol L(-1)). Etoposide
      (ET) and etoposide loaded polysorbate 20 micelles (EPM) were radiolabeled with
      99mTc by the reduction method using stannous chloride. Labeling parameters were
      optimized to obtain high labeling efficiency. The diethylenetriaminepentaacetic
      acid and cysteine challenge tests showed very low transchelation of 99mTc-ET and
      99mTc-EPM complexes indicating their in vitro stability. The complexes also
      exhibited serum stability assessed by ascending thin layer chromatography.
      Subcutaneous injection of EPM resulted in significantly higher tumor uptake ( 100
      folds compared to ET 6 h post injection) (p < 0.001) and prolonged tumor
      retention. Tumor uptake was also confirmed by gamma imaging studies. EPM
      exhibited relatively high brain concentrations ( 7 fold 24 h post injection)
      compared to ET, suggesting the potential use of EPM in the treatment of brain
      malignancies.

PMID- 16613723
TI  - 3D-QSAR CoMFA/CoMSIA studies on 5-aryl-2,2-dialkyl-4-phenyl-3(2H)-furanone
      derivatives, as selective COX-2 inhibitors.
AB  - Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity
      Indices Analysis (CoMSIA) were performed on a series of 5-aryl-2,2-dialkyl-4
      phenyl-3(2H)-furanone derivatives, as selective cyclooxygenase-2 (COX-2)
      inhibitors. Ligand molecular superimposition on the template structure was
      performed by the atom/shape based root mean square fit and database alignment
      methods. Removal of three outliers from the initial training set of 49 molecules
      improved the predictivity of the model. The statistically significant model was
      established of 36 molecules, which were validated by a test set of ten compounds.
      The atom and shape based root mean square alignment (IV) yielded the best
      predictive CoMFA model [R2(cv) = 0.664, R2 (non-cross-validated square of
      correlation coefficient) = 0.916, F value = 47.341, R2(bs) = 0.947 with six
      components, standard error of prediction36 = 0.360 and standard error of
      estimate36 = 0.180] while the CoMSIA model yielded [R2(cv) = 0.777, R2 (non-cross
      validated square of correlation coefficient) = 0.905, F value = 66.322, R2(bs) =
      0.933 with four components, standard error of prediction36 = 0.282 and standard
      error of estimate36 = 0.185]. The contour maps obtained from 3D-QSAR studies were
      appraised for activity trends for the molecules analyzed. Results indicate that
      steric, electrostatic, hydrophobic (lipophilic) and hydrogen bond donor
      substituents play a significant role in COX-2 inhibitory activity and selectivity
      of the compounds. The data generated from the present study will further help
      design novel, potent and selective COX-2 inhibitors.

PMID- 16613724
TI  - Amino acid derivatives. Part I. Synthesis, antiviral and antitumor evaluation of
      new alpha-amino acid esters bearing coumarin side chain.
AB  - A series of amino acid esters bearing coumarin (3-15) were synthesized and
      evaluated, in vitro, against HIV-1, and bovine viral diarrhea virus (BVDV). The
      in vitro cytotoxicity of 3-10 and 12 was assayed against a panel of tumor cell
      lines consisting of CD4 human T-cells. Compound 14 showed inhibition of HIV-1
      with EC50 > 1.6 microg mL(-1), meanwhile compound 9 exhibited activity against
      leukaemia (MT4) with CC50 = 24 micromol L(-1).

PMID- 16613725
TI  - Novel colorimetric assay of indomethacin using 4-carboxyl-2,6-dinitrobenzene
      diazonium ion.
AB  - A simple, sensitive and direct colorimetric method for the determination of
      indomethacin either in pure form or in capsules has been developed. The method is
      based on the diazo coupling reaction between indomethacin and a highly reactive
      arenediazonium ion, 4-carboxyl-2,6-dinitrobenzene diazonium ion, with the
      consequent formation of an azo dye. The reaction is fast and gave an orange azo
      dye in ethyl acetate. The assay was carried out at 470 nm and the azo adduct was
      stable for three hours. Beer's law is obeyed in the concentration range of 3.3-11
      microg mL(-1) of indomethacin. Optimization studies established an optimum
      reaction time of 20 minutes at 30 degrees C and the drug-to-reagent ratio of 1:2
      for optimal detector response. The method developed has a low limit of detection
      of 0.90 microg mL(-1) and is precise (RSD 2.3%). The new method has been
      successfully applied to the determination of indomethacin in capsules and the
      method is of equivalent accuracy as the official (BP) spectrophotometric method.
      The new method could find application as a simple analytical method for the assay
      of indomethacin in capsules.

PMID- 16613726
TI  - Synthesis of some new testosterone derivatives fused with substituted pyrazoline
      ring as promising 5alpha-reductase inhibitors.
AB  - Condensation of 3beta-hydroxy-16-[(4-chlorophenyl)methylene]androst-5-en-17-one
      (1) with hydrazine hydrate in acetic acid afforded N-acetyl pyrazoline derivative
      2, while condensation of 1 with semicarbazide afforded compound 3. Also, compound
      1 was treated with hydrazine hydrate in absolute methanol or ethanol to afford
      the corresponding alpha-methoxy (4) and alpha-ethoxy (5) derivatives, which were
      cyclized with etherated boron trifluoride to the pyrazoline derivative 6. The
      latter could be prepared directly by refluxing 1 with hydrazine hydrate in
      dioxane. Oxidation of compound 6 with Oppenour or Moffat oxidizing agents yielded
      3-oxo-derivatives 7 and 8, respectively. On the other hand, condensation of
      compound 1 with substituted hydrazines, gave the corresponding 3beta
      hydroxyandrostenopyrazolines 9a,b, which were oxidized using the Moffat method to
      give 3-oxo-androstenopyrazolines 10a,b, which were condensed with ethylene
      triphenyl-phosphorane in DMSO to yield 3-ethylene androstenopyrazolines 11a,b.
      Dehydrogenation of 9a,b with Wettestein oxidation afforded Delta4,6-diene-3-one
      analogues 12a,b, which were treated with chloranil to yield Delta(4,6,8(14))-tri
      ene-3-one analogues 13a,b. Oppenour oxidation of 9a,b afforded Delta4-ene-3-one
      analogues 14a,b, which were treated with dichlorodicyanoquinone (DDQ) in dioxane
      to give Delta1,4,6-triene-3-one analogues 15a,b. Pharmacological screening showed
      that many of these compounds inhibit 5alpha-reductase activity.

PMID- 16613727
TI  - Effects of pressure sensitive adhesives and chemical permeation enhancers on the
      permeability of fentanyl through excised rat skin.
AB  - Drug-in-adhesive patches (DIAPs) of fentanyl were formulated using various
      pressure sensitive adhesives (PSAs) and various chemical permeation enhancers
      (CPEs). The effects of PSAs and CPEs on skin permeation of fentanyl from DIAPs
      were evaluated using modified jacketed Franz diffusion cells fitted with excised
      rat abdominal skin. It was demonstrated that the permeation rate or steady state
      flux (J(ss)) of the drug through the excised rat skin was dependent on the
      viscosity and type of acrylic PSA as well as the type of CPE. Among different
      acrylic PSAs, Duro-Tak 2054 and Duro-Tak 2516 showed the highest J(ss) of 1.95
      microg cm(-2) h(-1) and the lowest J(ss) of 1.43 microg cm(-2) h(-1),
      respectively. Among the various CPEs used, propylene glycol and polyethylene
      glycol 400 showed 1.61 and 1.18, the highest and the lowest enhancement ratios
      (ER) of the skin permeation of fentanyl, respectively. Oleic acid and cetyl
      alcohol moderately increased the skin permeation of fentanyl. It was also shown
      that increasing the concentration of CPE led to reduction in the adhesion
      property of PSA as measured by the 180 degrees peeling strength test. Moreover,
      it was found that the permeation rate increased as the fentanyl loading increased
      from 1 to 3%. The skin permeation rate of fentanyl did not increase significantly
      beyond 3% drug loading. It was concluded that propylene glycol as a CPE and
      cosolvent in 10% (m/m) with 3% fentanyl loading in Duro-Tak 2054 showed an
      effective monolithic DIAP for the development of a transdermal therapeutic system
      for fentanyl.

PMID- 16613728
TI  - Synthesis and biological evaluation of some pyrimidine, pyrimido[2,1
      b][1,3]thiazine and thiazolo[3,2-a]pyrimidine derivatives.
AB  - 4,6-Diamino-1H-pyrimidine-2-thione (1) was used for the preparation of pyrimidine
      derivatives 2-5. Compound 5 was cyclized to produce pyrimido[2,1-b][1,3]thiazine
      derivative 6 which was condensed with p-chlorobenzaldehyde to give compound 7.
      The latter compound was reacted with hydroxylamine to give isoxazolo[4,5
      d]thiazino[2,3-a]pyrimidine 8. Compound 8b was treated with 2-chloroethyl methyl
      ether to afford compound 9. Similarly, compound 3 reacted with chloroacetic acid
      to give thiazolo[3,2-a]pyrimidine 10, which was condensed with p
      chlorobenzaldehyde to give compound 11. Compound 11 was condensed with
      hydroxylamine to give isoxazolo[4,5-d]thiazolo[2,3-a]pyrimidine 12. Compound 12b
      was treated with 2-chloroethyl methyl ether to afford compound 13. Biological
      evaluation of some prepared products showed that many of them revealed promising
      antimicrobial activity.

PMID- 16613729
TI  - Qualitative and quantitative analysis of flavonoids of the strawberry tree -
      Arbutus unedo L. (Ericaceae).
AB  - The leaves and fruits of strawberry tree - Arbutus unedo L., collected from two
      separate geographic locations in Croatia were investigated to determine their
      flavonoid composition and content. Quercitrin, isoquercitrin, hyperoside and
      rutin were identified in all leaf samples by means of thin-layer chromatography;
      the fruits contained only isoquercitrin. Chlorogenic acid was present in some
      leaf samples. The content of flavonoids depended on the plant organ investigated,
      date of collection and the locality. Spectrophotometric determination of the
      flavonoids indicated that the leaves are richer in flavonoids (0.52-2.00%) than
      fruits (0.10-0.29%).

PMID- 16613730
TI  - Esterification of 7-theophyllineacetic acid with diethylene glycol monomethyl
      ether.
AB  - The kinetics of esterification of 7-theophyllineacetic acid with diethylene
      glycol monomethyl ether in the presence of dicyclohexylcarbodiimide and 4
      dimethylaminopyridine as catalyst was studied. According to the known mechanism,
      besides the main process, the side-reaction of intramolecular rearrangement with
      formation of pharmacologically active N-acylurea occurs. The course of the main
      and the side-process was monitored by RP-HPLC with UV-detection. For that
      purpose, quantification of both ester and N-acylurea in the reaction mixture was
      performed. Influence of the concentration of the reactants (acid, alcohol and
      catalyst) on the progress of esterification and preparation of the by-product was
      investigated. Based on the obtained results, the reaction conditions leading to
      maximal yield of the ester and N-acylurea are proposed. The possibility of
      turning esterification to the synthesis of the side-product was also found.
      Reactions of the preparation of both the ester and N-acylurea were found to
      follow first-order kinetics. The rate constants of both processes were estimated.

PMID- 16613731
TI  - Oxidative stress assays for disease risk stratification.
AB  - Despite the fact that oxidative stress is a significant aetiological factor in
      several degenerative diseases, its measurement is rarely a part of "routine
      analyses" performed in hospital clinical chemistry laboratories. This situation
      is likely to change, as interest in this topic is increasing rapidly. Here we
      review the pertinent literature, with an assessment of assays for oxidative
      stress, and categorize them under: (i) assays for monitoring lipid peroxidation,
      (ii) assays for measuring oxidized amino acids, (iii) assays for measuring
      oxidized nucleic acids, (iv) assays based on physicochemical and immunological
      properties of oxidized low-density lipoprotein, and (v) assays for measuring the
      antioxidant capacity of body fluids and tissues. Our overview should be of help
      when choosing appropriate laboratory assays for oxidative stress and for routine
      disease risk stratification.

PMID- 16613732
TI  - Glycoscience -- a new frontier in rational drug design.
AB  - Glycans are the most abundant and most diverse biopolymers in nature. Because of
      their highly specific interactions with physiological receptors, they participate
      in many crucial biological processes. All these processes are potential targets
      for therapeutic intervention, and carbohydrate-based drugs are rapidly being
      taken up by the modern biotechnology and pharmaceutical industry. Recent
      developments in the field of glycobiology have overcome the problem of glycan
      analysis and synthesis; and many compounds based on carbohydrates are now in
      various stages of clinical trials. This article presents glycoproteins in a new
      light, as an important biopharmaceutical target, giving an overview of their
      potential use as therapeutic glycoproteins and proteoglycans, inflammation
      blockers, cancer therapeutics and vaccines, inhibitors of pathogenic microbes,
      viral inhibitors and potential aids in the treatment of lysosomal diseases,
      neurological diseases and transplantation rejection.

PMID- 16613733
TI  - Synthesis of 1-acyl-2-alkylthio-1,2,4-triazolobenzimidazoles with antifungal,
      anti-inflammatory and analgesic effects.
AB  - Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized
      through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The
      resulting 1,2,4-triazolo[2,3-a]benzimidazole-2-thione intermediate reacted with
      one equivalent of the alkyl halide to give the corresponding 2-alkylthio
      derivative 3a-g. The latters were acylated to afford the 1-acyl-2-alkylthio-1,2,4
      triazolo[2,3-a]-benzimidazole derivatives 4-10 in good yields. Structures of the
      new compounds were verified on the basis of spectral and elemental methods of
      analyses. Fourteen of the prepared compounds were tested for their possible
      antifungal activities. Most of the tested compounds showed activity against
      Candida albicans and Fusarium oxysporum comparable to that of fluconazole as a
      reference drug. Compounds 8a, 9a, and 10d are the most active ones against most
      of the fungi used. Compounds 3e, 4d, 5d, 6d, 7d, 8c, 8d, 9d, and 10d were tested
      for their anti-inflammatory and analgesic effects; most of these compounds showed
      potent and significant results compared to indomethacin. Moreover, ulcerogenicity
      and the median lethal dose (LD(50)) of the most active compound 8d were
      determined in mice; LD(50) was found to be 275 mg kg(-1) (i.p.).

PMID- 16613734
TI  - Design and evaluation of bilayer floating tablets of captopril.
AB  - The objective of the present investigation was to develop a bilayer-floating
      tablet (BFT) for captopril using direct compression technology. HPMC, K-grade and
      effervescent mixture of citric acid and sodium bicarbonate formed the floating
      layer. The release layer contained captopril and various polymers such as HPMC
      K15M, PVP-K30 and Carbopol 934p, alone or in combination with the drug. The
      floating behavior and in vitro dissolution studies were carried out in a USP 23
      apparatus 2 in simulated gastric fluid (without enzyme, pH 1.2). Final
      formulation released approximately 95% drug in 24 h in vitro, while the floating
      lag time was 10 min and the tablet remained floatable throughout all studies.
      Final formulation followed the Higuchi release model and showed no significant
      change in physical appearance, drug content, floatability or in vitro dissolution
      pattern after storage at 45 degrees C/75% RH for three months. Placebo
      formulation containing barium sulphate in the release layer administered to human
      volunteers for in vivo X-ray studies showed that BFT had significantly increased
      the gastric residence time.

PMID- 16613735
TI  - Paraoxonase/arylesterase in serum of patients with type II diabetes mellitus.
AB  - The aim of this study was to determine whether the paraoxonase (PON1) status,
      i.e. PON1 activities and phenotypes (AA, AB and BB), and its relationship with
      lipid status are different in patients with type II diabetes as compared to
      healthy population. Diabetic group comprised 175 patients with type II diabetes
      mellitus (94 men and 81 women) who came to their regular control examination and
      took the oral glucose tolerance test. Patients with type II diabetes mellitus
      diagnosis for 12 years on average were on peroral antidiabetics, or insulin or
      diet, and 3 patients had no therapy prescribed yet. Control group comprised 114
      apparently healthy individuals (28 men and 86 women) who were not on any
      medication. The paraoxonase activity was measured with 2.0 mmol L(-1) paraoxon in
      the absence and in the presence of 1.0 mol L(-1) NaCl, and with 2.0 mmol L(-1)
      phenylacetate. Both activities were measured spectrophotometrically at 37 degrees
      C in 0.1 mol L(-1) Tris-HCl buffer, pH = 8.0, containing 2.0 mmol L(-1) CaCl(2).
      Sera of diabetic and control subjects were assigned to the paraoxonase phenotypes
      on the basis of the basal paraoxonase activity distribution. We assigned 45% sera
      of male and 49% sera of female diabetic patients, and 64% sera of both genders of
      the control group to the AA low activity phenotype. There were no differences in
      paraoxonase activities between the gender- and phenotype-matched diabetic and
      control groups. Enzyme activity against the phenylacetate was higher, and
      phenotype-dependent, only in diabetic patients. In contrast to AA phenotype
      individuals, total cholesterol and LDL-cholesterol in the female diabetic group
      and triglyceride concentration in the male diabetic group assigned to pooled AB
      and BB phenotypes were higher than in the corresponding controls. It follows from
      PON1 phenotype distribution that less antiatherogenic paraoxonase B allele is
      more frequent in type II diabetes mellitus than in the healthy population. Their
      lipid status is more atherogenic, which could indicate a risk of premature
      atherosclerosis.

PMID- 16613736
TI  - Determination of cadmium in wine by electrothermal atomic absorption
      spectrometry.
AB  - A method is described for direct electrothermal atomic absorption spectrometric
      (ETAAS) determination of cadmium in untreated samples of wine. Pyrolytic graphite
      tubes and graphite tubes with standard L'vov pyrolytic platforms were tested as
      atomizers. The detection limit achieved was 0.08 microg L(-1) Cd in wine. The
      relative standard deviation for the concentration range from 0.2 to 10 microg L(
      1) Cd ranged from 1 to 7%. The accuracy of the method was confirmed by comparing
      the current results with those found for wet digested wine samples and by the
      analysis of spiked samples. By applying the proposed method it was found that the
      cadmium concentration in Macedonian wines ranges from 0.10 to 0.90 microg L(-1).

PMID- 16613737
TI  - Synthesis and characterization of carbazole derivatives and their antimicrobial
      studies.
AB  - The reaction of 1-oxo-1,2,3,4-tetrahydrocarbazoles (1a-e) with paraformaldehyde
      and ethylenediamine yielded N,N'-bis(1,2,3,4-tetrahydrocarbazol-1-ylidene)ethane
      1,2-diamines (2a-e). Here, like in another similar attempt of replacing
      ethylenediamine by ethanolamine, ended up in formation of 2-{[1-(2-(2
      aminoethoxy)ethylimino)-1,2,3,4-tetrahydrocarbazol-2-yl-methyl]amino}ethanols (3a
      e). These products were characterized by IR, (1)H NMR, mass spectra and by
      elemental analysis. All end products (2a-e, 3a-e) were screened for antibacterial
      and antifungal activities. The compounds having substituents at C-6 position were
      found to exhibit pronounced antimicrobial activities.

PMID- 16613738
TI  - Effect of acarbose on alanine aminotransferase and aspartate aminotransferase
      activities in the liver of control and diabetic CBA mice.
AB  - The purpose of this study was to examine the short-term effects of diet
      containing 0.1% (m/m) of acarbose in standard laboratory chow on specific liver
      enzyme activities: alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST) in control and diabetic CBA mice. Diabetes was induced by intravenous
      injection of alloxan monohydrate in a dose of 75 mg kg(-1) mouse body mass seven
      days before the treatment with acarbose. There were four groups of CBA mice in
      the experiment: control (C) mice (n = 6) and diabetic (D) mice (n = 8) fed
      standard chow; control (C/A-100) mice (n = 8) and diabetic (D/A-100) mice (n = 8)
      fed standard chow containing 0.1% acarbose. Diabetes induced a decrease of the
      ALT catalytic activities to 69.6% of the control value. A similar level of
      decreased ALT catalytic activity was detected in the liver of control and
      diabetic mice fed chow containing 0.1% acarbose. No changes in the specific and
      total activities of AST in the liver of experimental groups were observed.

PMID- 16613739
TI  - Kinetics and activity of arylsulfatase A in leukocytes derived from patients with
      cerebral palsy.
AB  - Activity and kinetics of arylsulfatase A (ASA, EC 3.1.6.8) were analyzed in
      leukocyte homogenates derived from patients suffering from cerebral palsy. Lower
      ASA activity was found in the patients' leukocytes than in controls, as
      determined by spectrophotometry using chromogenic substrate p-nitrocatechol
      sulfate (p-NCS). Kinetic parameters, K(m) and v(max), for leukocyte ASA were
      determined from the dependence of initial reaction velocities on the p-NCS
      concentrations. A slight difference in K(m) values was found for leukocyte enzyme
      in cerebral palsy (0.26 mmol L(-1)) compared to the control (0.21 mmol L(-1)),
      whereas v(max) value for leukocyte ASA in disease reached only 58% of the control
      value. In addition, the presence of the most common mutations associated with ASA
      pseudo-deficiency (N350S, 1524+95 A>G) and metachromatic leukodystrophy (P426L)
      was detected in all investigated patients. Changes in activity and kinetic
      parameters of leukocyte ASA in cerebral palsy are most probably related to the
      decrease of enzyme concentration; the detected mutations might at least partially
      contribute to the observed changes.

PMID- 16613740
TI  - Properties of the copper(II)-histidine complex obtained after dialysis of human
      plasma with histidine.
AB  - The copper(II)-histidine complex obtained following dialysis of human plasma with
      histidine was investigated using various types of extraction systems and ion
      exchange resins. According to the results obtained, the Cu(II)-histidine complex
      formed under the dialysis conditions has one positive charge. Preconcentration of
      copper from the dialysis solution was achieved by its extraction as a
      dithiocarbamate complex and by sorption on cation-exchange resin or onto chelate
      sorbent.

PMID- 16613741
TI  - The Charnley hip replacement -- 43 years of clinical success.
AB  - The Charnley low-frictional torque arthroplasty of the hip with 22.225 mm
      diameter head and thick ultra high molecular weigh polyethylene cup, both
      components grouted with cold curing acrylic cement, has reached 43 years of
      clinical success. Follow-up past 30 years is now available. Over 96% of patients
      are satisfied with the result. Post operative activity level is a reflection of
      patient selection. The neuropathic nature of the new joint does not reflect the
      mechanical state of the arthroplasty: regular follow-up with good quality
      radiographs is essential. Revisions may have to be undertaken for asymptomatic
      radiographic changes: a principle that must be understood and accepted before the
      primary procedure. The long-term problems are wear and cup loosening and strain
      shielding of the proximal femur. Long-term success will be further extended by
      understanding and practical application of the principles at the primary
      procedure and use of low wear materials for the articulation. The operation of
      total hip arthroplasty marks the beginning and not the end of treatment.

PMID- 16613742
TI  - [Treatment of congenital pseudarthrosis of tibia by vascularized fibular graft].
AB  - PURPOSE OF THE STUDY: The aim of the study was to evaluate the results in a group
      of patients with congenital pseudarthrosis of the tibia treated by transfer of a
      vascularized fibular graft from the contralateral extremity. MATERIAL: The group
      included three boys and two girls aged 2 to 8 years at the time of surgery. In
      two patients, the vascularized graft transfer was preceded by other operations.
      All patients but one had Crawford type IV pseudarthrosis. The signs of peripheral
      neurofibromatosis were found in four of the five patients. METHODS: The operation
      was carried out by two surgical teams, i. e., orthopedic and microsurgery
      (plastic surgery) specialists. Deep dissection of the pseudarthrosis was
      performed down to healthy, well vascularized tissue; a vascularized pedicle bone
      graft was harvested from the contralateral fibula. The graft was inserted and
      anchored intramedullarily in both tibial fragments, and stability was provided
      with a K-wire introduced through the calcaneus. Subsequently, the vascular
      pedicle of the fibular graft was joined to the surrounding vessels (anterior
      tibial artery and anterior tibial vein). The extremity was immobilized in plaster
      cast and later a KAFO brace was applied. RESULTS: Graft union partially failed in
      the proximal end of the graft due to bone resorption of both the graft and the
      proximal tibial fragment in two patients. This was successfully treated by
      additional spongioplasty. In all patients bony union was achieved at an average
      time of 9.8 months (range, 6 to 21 months). An increase by more than 100 % in the
      diameter of the transplanted fibula was recorded in four patients. The increase,
      which was of course related to follow-up time, was a clear proof of primary graft
      vascularization. DISCUSSION: The use of vascularized fibular graft harvested from
      the contralateral extremity showed high effectiveness in comparison with other
      methods. This was in agreement with the relevant literature reports. CONCLUSIONS:
      This method can be used regardless of patients' age and our experience showed
      that, even in small children, union can be achieved and can thus allow for early
      weight-bearing and prevention of crus atrophy.

PMID- 16613743
TI  - [Scarf osteotomy for the treatment of forefoot deformity].
AB  - PURPOSE OF THE STUDY: The outcome of surgical treatment in hallux valgus is
      sometimes unsatisfactory for both the patient and the surgeon. The valgus
      position of the big toe in the metatarsophalangeal joint is associated with a
      deviation to varus of the first metatarsal, resulting in the space between the
      first and second metatarsals called the intermetatarsal (IMT) angle. In most
      patients the angle is between 10 and 20 degrees. These patients were indicated
      for scarf osteotomy as this method has been reported to achieve good outcomes.
      The results are compared with the relevant literature data on foot osteotomy.
      MATERIAL: Our group involved 62 scarf osteotomies carried out on 49 patients who
      were followed up for an average of 18 months (range, 6-36 months). Three patients
      underwent surgery on both feet in one stage, five had bilateral surgery in two
      stages. The average pre-operative IMT angle was 16 degrees (range, 9-21 degrees)
      and the average hallux valgus angle was 37 degrees. METHODS: The patients were
      indicated for surgery on the basis of subjective complains and weight-bearing
      radiographs. Scarf osteotomy was performed by the Barouk technique. From a signle
      incision in the first intermetatarsal space, the lateral articular capsule was
      released, adductor tendon was dissected and sesamoid bones were reduced. The
      first metatarsal was exposed from an incision along its medial axis, the bunion
      was excised and Z-osteotomy of the metatarsal was performed. The distal fragment
      was shifted laterally, fixed with two 3.5 mm Poldi screws, and the capsule was
      closed under tension with transosseal suture. If necessary, an additional
      procedure on the big toe phalanges or osteotomy of the other metatarsals are
      carried out. From the second post-operative day the patients were allowed to walk
      on the heel, after removal of sutures they walked wearing a special sandal and,
      from the third week onwards, full weight-bearing was allowed. The average
      hospital stay lasted 4 days. The evaluation of post-operative results was based
      on radiograms, subjective feelings of the patients and clinical assessment of the
      range of big toe motion. RESULTS: Out of 62 operations carried out on 49 patients
      (average age, 41.5 years), 23 were performed on the right and 23 on the left
      foot; bilateral surgery was carried out in three patients in one stage and in
      five patients in two stages. Simultaneously, the Weil osteotomy was performed on
      six feet, Akin osteotomy of the big toe phalanges on five feet, Braggard surgery
      of the second toe on three feet, and scarf osteotomy of the fifth metatarsal on
      three feet. All feet were indicated for scarf osteotomy because of pain and, in
      56 feet, also esthetic reasons were involved. The patients' subjective post
      operative assessments were as follows: satisfaction with the outcome in 58 feet,
      pain associated with tight shoes in two feet, pain while walking in six feet, and
      dissatisfaction with the big toe shape in one patient.The average IMT angle of 16
      degrees and hallux valgus angle of 37 degrees on the pre-operative radiograms
      showed improvements to 9 degrees and 18 degrees, respectively, on the post
      operative X-ray. The sesamoid bones were reduced in all cases. After surgery the
      average range of motion was restricted as follows: plantar flexion by 7 degrees
      (to 23 degrees) and dorsal flexion by 6 degrees (to 54 degrees). The
      complications included one fracture of the head requiring osteosynthesis, one
      failure of fixation with repeat valgus osteotomy, three cases of insufficient
      correction of a valgus position that had to be treated by additional osteotomy of
      the first toe phalanges. DISCUSSION: Out of other types of osteotomy (Funk, Dega,
      spike osteotomy), outcomes similar to scarf osteotomy have been achieved only by
      the Austin procedure. However, in this, shifting of the distal fragment is
      limited and the results show that the Austin method should be preferred in
      deformities with an IMT angle of about 10 degrees. Scarf osteotomy in addition
      allows for early weight-bearing, does not produce shortening of the first
      metatarsal but permits its elongation and elevation by oblique osteotomy, if
      necessary. It can also be used for the fifth metatarsal. The drawbacks include a
      more complicated surgical technique and higher risk of complications; shifting of
      the distal fragment is also limited and, for this reason, scarf osteotomy is not
      effective in deformities with an IMT angle higher than 20 degrees. CONCLUSIONS:
      Scarf osteotomy is an effective procedure for a moderate valgus deformity of the
      big toe with an IMT angle between 10 and 20 degrees. It permits early weight
      bearing of the treated extremity. It requires exact pre-operative planning and
      strict adherence to the operative technique.

PMID- 16613744
TI  - [Arthroscopic stabilization of the shoulder].
AB  - PURPOSE OF THE STUDY: Minimally invasive technique have recently gained
      importance because of their apparent advantages. One of them is arthroscopic
      stabilization of the shoulder used for treatment of traumatic anterior
      glenohumeral dislocation with subsequent instability. In this study we describe
      the results of and experience with this technique. MATERIAL: Conventional
      treatment of glenohumeral dislocation, which includes reduction and subsequent
      immobilization for 4 weeks, has a high risk of recurrent dislocation particularly
      in young patients.Therefore surgical treatment lowering this risk is preferred.
      Arthroscopic stabilization is effective in patients with post-traumatic anterior
      instability of the glenohumeral joint. This technique involves fixation of the
      torn glenoid labrum and reduction of the anterior articular space. The evaluation
      of 77 patients treated by this method is presented here. METHODS: The
      arthroscopic method of labrum fixation with Mitek anchors (Mitek, Norwood, Mass.,
      USA) was used. Arthroscopic stabilization is carried out in a lateral recumbent
      position with an extension device, using two standard arthroscopic ports. After
      preparation of the glenoid rim, the torn labrum is sutured to GII anchors
      inserted in pre-drilled tunnels in the edge of the glenoid. Insertion of three
      anchors appears optimal, because the use of fewer anchors may result in failure
      and repeat dislocation. The anchors have to be inserted in a manner ensuring
      fixation of maximum of the torn labrum. RESULTS: A total of 90 shoulder joints
      were treated by arthroscopic stabilization and 77 patients were followed up.
      Excellent results were achieved in 58 patients (75.4 %). Good results in 14
      joints (18.2 %) and poor in 4 patients (5.2 %). Three repeat dislocations were
      recorded and one patient experienced restriction of motion in the treated
      shoulder. DISCUSSION: The three repeat dislocations (3.9 %) correlate with the
      results reported in the recent relevant literature. CONCLUSIONS: Arthroscopic
      shoulder joint stabilization is a reliable method. It is a surgical procedure
      suitable for treatment of shoulder instability and is also indicated in patients
      with acute traumatic dislocation, because it significantly reduces the risk of
      recurrent dislocation that is high in conventional treatment. In the hands of an
      experienced surgeon this technique is fast and simple and, because of its minimal
      invasiveness, convenient for the patient. In comparison with open stabilization
      techniques, arthroscopy is associated with higher failure, but a classical open
      procedure can still be used for treatment of recurrent dislocations.

PMID- 16613745
TI  - [Measurement of acetabular polyethylene wear of total hip replacement, using a
      universal measuring microscope. Characteristics of measurements].
AB  - PURPOSE OF THE STUDY: The aim of the study was to present our own method of
      measuring acetabular polyethylene wear in total hip arthroplasty, including
      assessment of basic measurement characteristics. It is a well known fact that, in
      total hip replacement, polyethylene liners wear out with use. The rate of
      acetabular polyethylene wear can then be related to clinical or demographic data.
      MATERIAL AND METHODS: Our method, using a universal measuring microscope, is
      based on the ability of exact identification of central positions of the head of
      total hip replacement before implantation and after prosthesis removal. The
      difference between the original and final positions allows us to calculate both
      linear and volumetric wear of polyethylene. During one month, the same components
      were repeatedly measured by two independent investigators and a total of 10 ABG 1
      acetabular components were checked. The results of measurements were evaluated by
      a series of statistical tests, including correlation and regression analyses and
      analysis of variance. RESULTS: High correlations were found among individual
      measurements made by each observer (r = 0.998; r = 0.973) as well as between the
      mean values obtained from the two observers (r = 0.996). The reliability of
      measurements was proved by a high correlation of the regression curve of each
      measurement with the "ideal" line. With two exceptions, the differences between
      paired measurements were not significant. CONCLUSIONS: Our method facilitates an
      in vitro measurement of polyethylene wear with considerable accuracy and high
      reliability.

PMID- 16613746
TI  - [Use of post-operative drainage and auto-transfusion sets in total knee
      arthroplasty].
AB  - PURPOSE OF THE STUDY: The aim of the study was to show advantages of post
      operative collection of shed blood and its return to the patient's circulation,
      using blood-reinfusion sets, in terms of requirements for homologous blood,
      transmission of infections and posttransfusion reactions in total knee
      arthroplasty. MATERIAL: Two groups of patients were studied. In group 1,
      comprising 88 patients, shed blood was collected by means of sets for post
      operative wound drainage and subsequent autotransfusion. In group 2, with 44
      patients, the standard Redon drainage system was used and blood losses were
      compensated for by homologous blood. Osteoarthrosis of the knee joint was the
      indication for total knee arthroplasty. Patients with a hemoglobin level lower
      than 110 g/l, rheumatoid arthropathy, hemophilic arthropathy, coagulopathy,
      infectious or cancer diseases, or liver or kidney failure were not included, as
      well as patients who were treated with non-steroid anti-rheumatic drugs, steroids
      or anticoagulation drugs. METHODS: Post-operative blood losses within 6 h of
      surgery, by 24:00 hours on the day of operation and on the 1st and 2nd
      postoperative days were recorded. The amount of returned blood and requirements
      for homologous blood transfusion were also recorded. None of the patients had
      donated autologous blood. The patients were examined for blood pressure and heart
      rate; their body temperature was taken, blood samples were collected for blood
      cell counts and ion (Na(+), K(+), C1(-)) assessment, and urine samples were
      collected for laboratory tests. All side-effects and complications during
      hospitalization were recorded as well as all late consequences. The drainage
      systems used included Redyrob CAT, Retrans and Bellovac ABT. RESULTS: In group 1,
      the median value for total post-operative blood loss was 1065 ml, with the median
      reinfusion value of 500 ml; 31 % of the patients required homologous blood
      transfusion. In 36 % of the patients, body temperature increased by more than 1
      degrees C, as compared with the value before reinfusion, by 24:00 hours on the
      operative day, and in 2 % it was higher than 38.5 degrees C. No infection
      occurred in the early post-operative period, but late infectious complications
      resulted in reimplantation in one patient (1 %). In group 2, the median value of
      post-operative blood loss was 1045 ml and all patients received homologous blood
      transfusion. Post-operative complications directly related to blood reinfusion,
      such as febrile reaction, shivering, pruritus, blood pressure or heart rate
      fluctuation, renal failure or coagulopathy, were not recorded in either group.
      DISCUSSION: The use of drainage system allowed us to reduce the need for
      homologous blood transfusion by 63 %. Blood salvage reported in the relevant
      literature varies between 8 and 80 %, which reflects differences in views on lost
      blood compensation. The total blood loss in both our groups was in agreement with
      the data reported by other authors, and the same held true for the reinfusion
      volume; most of the authors recommend to use a maximum of 800 ml. A higher blood
      volume carries risks due to a high level of free hemoglobin. The recommended
      period of 6 h for blood reinfusion was respected (to eliminate potential
      complement activation). We assume that the temperature higher than 38.5 degrees C
      found in 2 % of our patients was caused by a changed environment and post
      operation reactions. The slightly higher losses recorded by 24:00 hours in group
      1 were caused, in our opinion, by the resetting of suction pressure after
      reinfusion had finished. This difference in shed blood was eliminated during the
      following day and the total losses were comparable in both groups. CONCLUSIONS:
      Our results showed that, in total knee arthroplasty, post-operative collection of
      shed blood and its reinfusion in the circulation can lower the need for
      homologous blood transfusion and reduce associated risks. If all conditions are
      observed, i. e., blood reinfusion within 6 h of surgery and the maximum of
      returned blood not exceeding 800 ml, the method is a safe way of compensating for
      blood losses in elective knee surgery.

PMID- 16613747
TI  - [Peripheral primitive neuroectodermal tumor -- PNET].
AB  - The authors describe three cases of peripheral primitive neuroectodermal tumor.
      The tumor was found in soft tissues of the crus, shoulder girdle and perineum,
      and was also located paravertebrally and epidurally at the level of L1-L2
      vertebrae. Radiological findings were not specific for this disease. The results
      of imaging methods (sonography, CT, MRI, DSA) were important for the assessment
      of tumor size, its boundary and invasion of the surrounding tissues, and for the
      evaluation of tumor response to therapy and detection of recurrent disease. The
      PNET diagnosis was based on immunohistochemical, biochemical and cytogenetic
      examinations. One patient died 5 months after the first clinical signs were
      manifested; the two patients surviving for 2 and 1 3/4 years after first sign
      manifestation, respectively, remained in the care of cancer specialists. Key
      words: skeletal Ewing's sarcoma, extra-skeletal Ewing's sarcoma, Ewing's sarcoma
      family of tumors, peripheral primitive neuroectodermal tumor.

PMID- 16613748
TI  - Fractures of the femoral neck: a review and personal statement.
AB  - EPIDEMIOLOGY: The number of hip fractures will increase enormously in the decades
      to come as will the cost of treatment of these patients do. In the USA the annual
      cost has estimated to be nearly $10 billion. Hip fractures, therefore, represent
      an enormous socio-economic and medical problem and challenge (orthopaedic)
      surgeons an anaesthetists to find the cheapest and most effective way to treat
      them. At the same time the search for preventive measures should be continued.
      Biphosphonates and hip protectors seem to be able to decrease the risk of
      suffering a hip fracture with 50%. CLASSIFICATION: The first classification of
      femoral neck fractures, proposed by Abraham Colles, in displaced and non
      displaced (impacted) fractures appears to be still the most useful one. The
      Pauwels classification cannot be applied to the preoperative x-ray, because the
      fractured leg is always in external rotation. The Garden classification is not
      reproducible and does not lead us to the right treatment. TREATMENT: Stability
      and healing chances of impacted fractures depend especially on age and general
      condition. In patients under 70 years of age without co-morbidity, the secondary
      instability rate after non-operative treatment is very low: 5%. In elderly people
      with multiple co-morbidity secondary instability can go up to 80%. These patients
      are better served with primary operative treatment. Although the majority of
      surgeons feel good with a strategy of prophylactic internal fixation in all
      patients, this author pleads for non-operative (early mobilization) treatment of
      all patients, who are healthy or have only one serious comorbidity. There is
      consensus about the treatment of displaced fractures in patients under 65 years
      of age: closed reduction and internal fixation. The best treatment for patients
      over 80 years of age is prosthetic replacement. In the (large) group of patients
      between 65 and 80 years of age calendar age is not a reliable guide to the right
      treatment. There is a growing conviction that the choice between internal
      fixation and prosthetic replacement in these patients should be made on the basis
      of the biological age (ASA-score, habitat, the activity level, the need for
      walking aids and cognitive function). Bone density does not seem to play an
      important role. If internal fixation is the preferred treatment, the choice of
      implant is controversial. It is the author's experience that fractures with a
      steep fracture line (Pauwels 3) should be anatomically reduced and stabilized
      with a sliding hip screw. The less steep fractures (Pauwels 1 and 2) can be
      slightly over-reduced in valgus and anteversion, which provides a bony support
      against shearing forces, and fixed with parallel screws according to the 3-point
      fixation principle. The timing of surgery continues to be a controversial
      subject. From a recent study in our own institution we concluded that no
      significant association could be found between delay to surgery and the clinical
      outcomes.However, considering the trends towards less complications and shorter
      length of hospital stay, early surgery (within 1 day from admission) is likely to
      be beneficial for hip fracture patients who are able to undergo operation. There
      is agreement about the use of the cemented arthroplasty. If a hemiarthroplasty is
      chosen, the bipolar type is to be preferred to the unipolar type. The difference
      in price between both prostheses is negligible because the overall cost of the
      treatment have gone up so immensely. Furthermore, a basic advantage of the
      bipolar system is the relatively small operation, needed for conversion to a
      total hip replacement, because the stem can stay in place. As to the question
      hemiarthroplasty or total hip replacement, the discussion has not yet been
      closed. We studied the natural history of the cemented bipolar hemiarthroplasty
      by evaluating 307 patients, operated between 1975 and 1989 in our institution.
      Only 3 patients, who not have been revised, were alive at the end of the
      observation period (2004). A striking difference was found in the occurrence of
      late mechanical complications (aseptic loosening and acetabular wear) between
      patients under 75 years of age (22%) and the older group of patients (6%). As to
      the patient's overall satisfaction 56% suffered no impairment from their
      sustained fracture, 36% were slightly impaired. We concluded that the use of the
      cemented bipolar prosthesis is justified in patients over 75 years of age.
      Patients between 65 and 75 years of age should either be treated with internal
      fixation or with a total hip replacement. NONUNION OF THE FEMORAL NECK: Nowadays
      in cases of nonunions of the femoral neck the surgeon is tempted to perform
      prosthetic replacement of the hip, the more so if there is also evidence of a
      disturbed vascularisation of the head. This will provide rapid pain relief and
      mobilization. However, long-term results of hip arthroplasties, especially in
      younger people and in presence of bone atrophy, are not always as expected and a
      less radical approach is worth considering. The intertrochanteric valgization
      osteotomy, described by Pauwels is an excellent alternative for patients up to 65
      years of age with a non-union of the femoral neck. A union rate of 80-90% is
      described by most authors. Leg length, rotational and angular deformities can be
      corrected at the same time. Between 65 and 80 years a total hip replacement is
      probably the best option for fit patients. For elderly patients a cemented
      bipolar hemiarthroplasty is an adequate treatment.

PMID- 16613749
TI  - Post-traumatic iatrogenic aggravation of eruptive collagenomas in a child.

PMID- 16613750
TI  - Chicken-wire erythema, but not urticaria, as the presenting sign of hereditary
      angioedema.

PMID- 16613751
TI  - Excimer-laser (308 nm) treatment of large plaque parapsoriasis and long-term
      follow-up.

PMID- 16613752
TI  - Disruption of skin natural tolerance by UV irradiation.

PMID- 16613753
TI  - Acrokeratoelastoidosis.

PMID- 16613754
TI  - Extramammary Paget's disease of the scrotum with Bowenoid features.

PMID- 16613755
TI  - Giant cell tumor of the distal phalanx of the foot.

PMID- 16613756
TI  - Immunohistochemical localization of activated Stat3 and hTERT protein in
      psoriasis vulgaris.

PMID- 16613757
TI  - Recent advances in the relationship between obesity, inflammation, and insulin
      resistance.
AB  - It now appears that, in most obese patients, obesity is associated with a low
      grade inflammation of white adipose tissue (WAT) resulting from chronic
      activation of the innate immune system and which can subsequently lead to insulin
      resistance, impaired glucose tolerance and even diabetes. WAT is the
      physiological site of energy storage as lipids. In addition, it has been more
      recently recognized as an active participant in numerous physiological and
      pathophysiological processes. In obesity, WAT is characterized by an increased
      production and secretion of a wide range of inflammatory molecules including TNF
      alpha and interleukin-6 (IL-6), which may have local effects on WAT physiology
      but also systemic effects on other organs. Recent data indicate that obese WAT is
      infiltrated by macrophages, which may be a major source of locally-produced pro
      inflammatory cytokines. Interestingly, weight loss is associated with a reduction
      in the macrophage infiltration of WAT and an improvement of the inflammatory
      profile of gene expression. Several factors derived not only from adipocytes but
      also from infiltrated macrophages probably contribute to the pathogenesis of
      insulin resistance. Most of them are overproduced during obesity, including
      leptin, TNF-alpha, IL-6 and resistin. Conversely, expression and plasma levels of
      adiponectin, an insulin-sensitising effector, are down-regulated during obesity.
      Leptin could modulate TNF-alpha production and macrophage activation. TNF-alpha
      is overproduced in adipose tissue of several rodent models of obesity and has an
      important role in the pathogenesis of insulin resistance in these species.
      However, its actual involvement in glucose metabolism disorders in humans remains
      controversial. IL-6 production by human adipose tissue increases during obesity.
      It may induce hepatic CRP synthesis and may promote the onset of cardiovascular
      complications. Both TNF-alpha and IL-6 can alter insulin sensitivity by
      triggering different key steps in the insulin signalling pathway. In rodents,
      resistin can induce insulin resistance, while its implication in the control of
      insulin sensitivity is still a matter of debate in humans. Adiponectin is highly
      expressed in WAT, and circulating adiponectin levels are decreased in subjects
      with obesity-related insulin resistance, type 2 diabetes and coronary heart
      disease. Adiponectin inhibits liver neoglucogenesis and promotes fatty acid
      oxidation in skeletal muscle. In addition, adiponectin counteracts the pro
      inflammatory effects of TNF-alpha on the arterial wall and probably protects
      against the development of arteriosclerosis. In obesity, the pro-inflammatory
      effects of cytokines through intracellular signalling pathways involve the NF
      kappaB and JNK systems. Genetic or pharmacological manipulations of these
      effectors of the inflammatory response have been shown to modulate insulin
      sensitivity in different animal models. In humans, it has been suggested that the
      improved glucose tolerance observed in the presence of thiazolidinediones or
      statins is likely related to their anti-inflammatory properties. Thus, it can be
      considered that obesity corresponds to a sub-clinical inflammatory condition that
      promotes the production of pro-inflammatory factors involved in the pathogenesis
      of insulin resistance.

PMID- 16613758
TI  - In vivo electrotransfer of interleukin-10 cDNA prevents endothelial upregulation
      of activated NF-kappaB and adhesion molecules following an atherogenic diet.
AB  - OBJECTIVES: Interleukin (IL)-10 has anti-atherogenic properties. However, the
      molecular mechanisms involved in IL-10 protection against atherosclerosis in vivo
      remain poorly understood. In this study, we examined the effect of IL-10 cDNA in
      vivo electrotransfer on diet-induced, endothelial activation. METHODS: C57BL/6J
      mice were fed an atherogenic diet for 10 days. Expression of VCAM-1 and ICAM-1
      was examined in the aortic sinus, a region predisposed to atherogenesis in mice,
      using immunohistochemistry. NF-kappaB activation was examined using a monoclonal
      antibody that selectively reacts with the activated form of the p65 subunit.
      RESULTS: We detected a low basal expression of activated NF-kappaB, VCAM-1 and
      ICAM-1 in the endothelium of the aortic sinus. Endothelial expression of
      activated NF-kappaB, VCAM-1 and ICAM-1 was markedly increased after 10 days on
      the atherogenic diet (p < 0.001). In vivo electrotransfer of a murine IL-10
      encoding plasmid completely prevented diet-induced endothelial upregulation of
      activated NF-kappaB, VCAM-1 and ICAM-1 (p < 0.01). CONCLUSION: In vivo
      electrotransfer of IL-10 cDNA prevents diet-induced endothelial activation. These
      results suggest that the protective effects of IL-10 may already occur in the
      very early stages of atherogenesis.

PMID- 16613759
TI  - Neutrophils process interleukin-1beta and interleukin-18 precursors in a caspase
      1-like fashion--processing is inhibited by human vascular smooth muscle cells.
AB  - Inflammation contributes to the pathogenesis of atherosclerosis. Proinflammatory
      cytokines, including interleukin-1 (IL-1), may be involved in the local
      inflammation occurring in the vessel wall. Vascular smooth muscle cells express
      the unprocessed IL-1beta precursor molecule. Invading leukocytes, such as
      monocytes or polymorphonuclear granulocytes (PMN) may activate the IL-1beta
      precursor during atherogenesis. Thus, we investigated the capacity of PMN to
      process IL-1beta and IL-18 precursors. Processing was analyzed using Western blot
      and bioassay for IL-1-activity was performed. As few as 80 to 400 PMN/mL
      detectably processed preIL-1beta. PMN also cleaved the caspase-1 substrate preIL
      18. The preIL-1beta and preIL-18 cleavage products were located at the same
      apparent molecular weight as those resulting from cleavage by monocyte-derived
      caspase-1. PMN expressed caspase-1 mRNA and immunoreactive protein. The N
      terminus of the preIL-1beta cleavage product expressed the sequence expected for
      caspase-1 cleavage. The cleavage product was active in the bioassay for IL-1
      activity, and the caspase-1 inhibitor YVAD blocked processing. We have shown
      previously that SMC can block processing of preIL-1 by caspase-1. In contrast,
      SMC do not block processing of PARP by caspase-3. Here, we show that SMC also
      inhibited the PMN-mediated processing of recombinant and native preIL-1beta or
      preIL-18 depending on the cell number, whereas EC or fibroblasts did not block
      processing. Our results indicate that PMN can activate preIL-1beta in a caspase-1
      like fashion. During inflammatory processes, PMN may activate preIL-1beta
      released from SMC, thereby altering IL-1-mediated cardiovascular functions,
      including contractility, apoptosis, and cytokine production.

PMID- 16613760
TI  - Toll-like receptor 4 Asp299Gly/Thr399Ile polymorphisms are a risk factor for
      Candida bloodstream infection.
AB  - Toll-like receptor (TLR)-4 is an important pattern recognition receptor for
      Candida albicans, playing a role in innate host defense. We investigated whether
      there is an association between the TLR4 Asp299Gly or TLR4 Thr399Ile
      polymorphism, and the occurrence of Candida bloodstream infection. We performed a
      case-control study, involving 43 patients with a Candida bloodstream infection
      and 166 healthy individuals. TLR4 Asp299Gly and Thr399Ile polymorphisms were
      assessed, as well as cytokine production after stimulation of peripheral blood
      mononuclear cells (PBMC) with Candida albicans. We observed that the prevalence
      of TLR4 Asp299Gly polymorphism was found to be higher in patients with Candida
      bloodstream infection than in controls (26% versus 10%; OR 3.0; 95%CI 1.3-6.9).
      All patients bearing the Asp299Gly polymorphism were also positive for the
      Thr399Ile allele, a linkage well described in literature. IL-10 production was
      higher in C. albicans-stimulated PBMC from volunteers bearing the TLR4 Asp299Gly
      polymorphism, and a similar tendency was observed in TLR4 Asp299Gly heterozygous
      patients who had recovered from candidemia. These findings show that the TLR4
      Asp299Gly/Thr399Ile polymorphisms are associated with an increased susceptibility
      to Candida bloodstream infections, and an increased production of IL-10 is
      probably involved in this effect.

PMID- 16613761
TI  - Development of a systemically-active dual CXCR1/CXCR2 allosteric inhibitor and
      its efficacy in a model of transient cerebral ischemia in the rat.
AB  - The chemokine receptors CXCR1 and CXCR2 present on polymorphonuclear neutrophils
      (PMN), bind the chemokine CXC ligand 8 (CXCL8)/interleukin-8 (IL-8), and have a
      key role in PMN recruitment in inflammation. Based on the structure of reparixin,
      a small-molecular-weight allosteric inhibitor of CXCR1, we designed a dual
      inhibitor of CXCR1 and CXCR2 with a longer in vivo half-life, DF2156A. This
      molecule inhibited human and rat PMN migration in response to CXCR1 and CXCR2
      ligands and showed an elimination half-life following i.v. administration, of 19
      hours. In a rat model of cerebral ischemia/reperfusion induced by temporary (90
      min) middle cerebral artery (MCA) occlusion, DF2156A (8 mg-kg, i.v., at the time
      of reperfusion) decreased the PMN infiltrate, infarct size and significantly
      improved neurological function. These results indicate that CXCR1/CXCR2 and their
      ligands have a role in the inflammatory component of cerebral ischemia, and that
      these pathways represent an important pharmacological target.

PMID- 16613762
TI  - The role of CXCR2 activity in the contact hypersensitivity response in mice.
AB  - The recruitment of polymorphonuclear neutrophil leukocytes (PMN) into a challenge
      site, and their subsequent activation, are thought to play a role in the
      elicitation of the contact hypersensitivity (CHS) response. The present study
      investigated the role played by CXCR2 activity in tissue PMN infiltration and
      subsequent triggering of CHS. Our results show that the cutaneous infiltration by
      PMN, induced by hapten challenge was dramatically inhibited in sensitized, CXCR2
      deficient (CXCR2(-/-)) mice. Inhibition of PMN recruitment into the hapten
      challenged ears of CXCR2(-/-) mice was associated with a consistent reduction of
      the CHS response (ear swelling) in CXCR2(-/-) mice as compared with that observed
      in neutropenic, wild-type (CXCR2(+/+)) mice. Prevention of skin PMN infiltration
      and the ear swelling response by the absence of functional CXCR2 was observed
      regardless of the hapten used. These data clearly suggest that CXCR2 activity
      plays an essential role in mediating cutaneous recruitment and activation of PMN,
      and thus indirectly regulates recruitment of hapten-primed T cells into challenge
      sites, with the subsequent elicitation of the CHS response. The role played by
      CXCR2 activity in the CHS response provides the rationale for testing CXCR2
      inhibitors as a new therapeutic approach to skin diseases.

PMID- 16613763
TI  - Synthetic chemokines directly labeled with a fluorescent dye as tools for
      studying chemokine and chemokine receptor interactions.
AB  - Chemokines constitute a protein family that exhibit a variety of biological
      activities involved in normal and pathological physiological processes. CCL11
      (eotaxin), CCL19 (MIP-3beta), CCL22 (MDC), CXCL11 (I-TAC) and CXCL12 (SDF-1alpha)
      chemokines, modified with the Alexa Fluor 647 fluorescent dye at specific
      positions along their sequence, were produced by a chemical route and their
      biological activities were characterized. In a migration assay, fluorescent
      chemokines were as biologically active as the unmodified forms. All labeled
      chemokines specifically stained cell lines transfected with the appropriate human
      chemokine receptors. The specificity of binding was further established by
      showing that the unlabeled ligands efficiently competed with the labeled
      chemokines for binding to their respective receptor. A low molecular weight
      antagonist of CXCR4 prevented binding of labeled CXCL12 to CXCR4 comparably to a
      neutralizing anti-CXCR4 antibody. Finally, labeled CCL19 was used for the
      staining of primary cells, illustrating that this reagent can be used for
      studying CCR7 expression on different cell types. Together, these results
      demonstrate that fluorescent synthetic chemokines constitute promising ligands
      for the development of chemokine receptor-binding assays on intact cells, for
      applications such as cell-based, high throughput screening, and studies of
      chemokine receptor expression by primary cells.

PMID- 16613764
TI  - Elevated IL-10 plasma levels correlate with poor prognosis in diffuse large B
      cell lymphoma.
AB  - The aim of the study was to confirm whether plasma levels of interleukin-10 (IL
      10) correlate with the prognosis in diffuse, large B-cell lymphoma (DLBCL)
      patients. Plasma IL-10 levels were determined at the time of diagnosis in a group
      of 157 consecutively treated, DLBCL patients. Of those, 122 patients (78%) had IL
      10 plasma levels below the detection limit (< 5 pg/mL) and 35 (22%) above this
      value. The median value for patients with detectable IL-10 levels was 35 pg/mL
      (range, 5 to 2480 pg/mL). Detectable plasma IL-10 levels were significantly
      associated with age > 60 years, ECOG performance status > or = 2, Ann Arbor
      advanced disease stage, bulky tumor mass, elevated serum levels of LDH and beta2
      microglobulin, presence of anemia and low serum albumin levels as well as the
      presence of B symptoms. The patients with detectable IL-10 levels had lower
      probability of CR achievement (OR = 0.23, 95% CI 0.1-0.5, p = 0.0003). In
      addition, detectable IL-10 levels were significantly associated with shorter PFS
      (OR = 2.5, 95% CI 1.5-4.4, p = 0.001) and OS (OR = 3.0, 95% CI 1.7-5.2, p =
      0.0001). In conclusion, we confirmed in this large group of DLBCL patients that
      elevated plasma IL-10 levels correlated with adverse disease features and poor
      prognosis. The plasma concentration of IL-10 may be a useful marker for
      evaluation of disease activity.

PMID- 16613765
TI  - Influence of a high carbohydrate diet on the functional activity of 5-HT1B/1D
      receptors on human peripheral blood lymphocytes during intense military training.
AB  - The present study was undertaken to examine the effect of a high carbohydrate
      diet on the functional activity of 5-HT1B/1D receptors in human peripheral blood
      lymphocytes, and on serum cortisol and plasma cytokine responses during intense
      military training. Thirty two male soldiers (mean age: 21 +/- 2 years) were
      randomly assigned to two groups and received either 3200 kcal/24 h [13440 kJ;
      habitual diet group (HD)] or 4200 kcal/24 h [17640 kJ, high carbohydrate diet
      group (HCD)] by adding 1000 kcal (4200 kJ) of fruit jelly to the HD. They took
      part in a three-week training program followed by a five-day combat course. Blood
      samples were collected from each group before entry into the commando training
      and after the five-day combat course. The results of [35S] GTPgammaS binding
      assays showed that h5-HT1B/1D receptors were desensitized after the training
      program in the HD group, whereas no change was observed between the beginning and
      the end of the military training in the HCD group [(HD : IC50 = 100 +/- 14 nM to
      544 +/- 178 nM; n = 16) and (HCD: IC50 = 68 +/- 14 nM to 101 +/- 22 nM; n = 16)].
      Serum cortisol was only significantly increased after the commando training in
      the HD group (from 532.2 +/- 30 to 642 +/- 45 nmol.L(-1), p < 0.05), whereas
      values were not significantly changed in the HCD group (441 +/- 31 to 502 +/- 40
      nmol.L(-1)). No changes were observed in IL-10, TNF-alpha and IFN-gamma levels
      after the training program in either group. Carbohydrate ingestion or additional
      dietary energy during repeated bouts of high-intensity exercise could attenuate
      the alterations in immune function via 5-HT1B/1D receptors and the action of 5-HT
      moduline, an endogenous tetrapeptide (Leu-Ser-Ala-Leu) that specifically
      modulates the sensitivity of 5-HT1B/1D receptors.

PMID- 16613766
TI  - Serum vascular endothelial growth factor and its receptor level in patients with
      chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a disorder which encompasses not
      only morphological changes in parenchyma, central and peripheral airways but also
      in structural and functional changes of pulmonary vessels. The role of angiogenic
      factors leading to abnormal pulmonary vessel remodeling remains unclear. We have
      investigated a cytokine vascular endothelial growth factor (VEGF) known to be
      involved in angiogenesis, and its soluble receptors (sVEGF R1, sVEGF R2) in the
      serum of 20 patients with mild COPD and 10 patients with very severe COPD, using
      sensitive enzyme-linked immunoassays. The control group consisted of 10 healthy
      volunteers. We found that the concentration of VEGF in the serum of patients with
      mild COPD was significantly higher (665.31 +/- 102.20 pg/mL) in comparison to the
      control group (318.94 +/- 51.40 pg/mL; p < 0.05), and there was a strong negative
      correlation with FEV1 (r = -0.859; p < 0.001). Additionally, the level of sVEGF
      R1 in the serum of patients with very severe COPD was also significantly higher
      (96.60 +/- 26.85 pg/mL) than in the control (36.01 +/- 3.29 pg/mL; p < 0.05) and
      a positive correlation between the serum level of sVEGF R1 and FEV1 was found (r
      = 0.748; p < 0.01). Moreover, we observed an insignificant increase of sVEGF R2
      in the serum of patients with mild COPD and those with very severe COPD. These
      results suggest that VEGF and sVEGF R1 receptor are involved in the development
      of abnormal pulmonary vascular remodelling in patients with COPD.

PMID- 16613768
TI  - [Risk stratification in non-ST segment elevation myocardial infarction].
AB  - Patients with either unstable angina or non ST elevation myocardial infarction
      are usually submitted to the emergency department with similar symptoms and
      signs. Generally cardiac enzyme determinations can differentiate these two
      conditions. Elevation of these enzymes and their detection in blood stream takes
      a certain amount of time. A number of studies demonstrated lately that the high
      risk patients benefit more aggressive treatment modalities. Risk stratification
      and identification of the high risk patients became an essential part of the
      evaluation in emergency departments.

PMID- 16613769
TI  - [Vulnerable high-risk plaque (thin cap fibroatheroma): vulnerable
      patient/vulnerable blood].
AB  - Coronary plaque disruption and subsequent thrombosis is the major recognized
      pathogenetic component of "vulnerable plaques", which characterize the transition
      from stable coronary artery disease to acute coronary syndromes. Autopsy studies
      have characterized a subgroup of high-risk, or vulnerable, plaques that result in
      acute coronary syndromes or sudden cardiac death. In recent years, cardiovascular
      research has sought potential strategies for detecting high-risk plaques before
      their disruption. This review focuses on definition of vulnerable plaque and
      vulnerable patients and the diagnostic modalities using identification of the
      vulnerable/high-risk plaques.

PMID- 16613770
TI  - [Antiplatelet therapy in acute coronary syndromes without ST segment elevation].
AB  - The pathophysiology of acute coronary syndromes involves plaque rupture or
      fissure with platelet activation and aggregation. Antiplatelet therapy is a
      cornerstone in the management of unstable angina and non-ST elevation myocardial
      infarction. Three classes of antiplatelet drugs have been found useful in the
      management of these patients: aspirin, thienopyridines and glycoprotein IIb/IIIa
      antagonists. There is a great amount of interpatient variability in response to
      these antiplatelet agents, and this variability may affect outcomes. It is needed
      to prescribe appropriate antiplatelet therapies according to potential benefit in
      reducing death and cardiovascular events vs the bleeding risks these agents
      cause. Antiplatelet drugs are the subjects of continued intensive investigation.

PMID- 16613771
TI  - [Antithrombotics (Antithrombin therapy)].
AB  - Thrombus on the atherosclerotic plaque is mainly responsible for acute coronary
      syndromes. Antithrombin therapy continues to be the mainstay of the therapy
      defeating thrombus. Up-to-date antithrombin therapy consists of vitamin K
      antagonists, unfractionated and low molecular heparins, direct thrombin
      inhibitors and selective inhibitors of factor Xa. Today, none of these drugs is
      effective enough in every aspect. The need for new antithrombin drugs, as well as
      the need for new antiplatelet drugs which can be safely and effectively used
      together with other antithrombin drugs, persists.

PMID- 16613772
TI  - [Early invasive treatment strategies in patients with non-ST-elevation acute
      coronary syndromes: which patients should be treated invasively?].
AB  - Early invasive strategy is a major therapeutic alternative in the treatment of
      patients with non-ST segment elevation acute coronary syndromes. In the recent
      randomised trials, there is a tendency supporting invasive strategy during the
      very early period of the disease and it is recommended routinely in almost all
      patients. Despite this strategy has a questionable effect on mortality per se,
      there is a remarkable benefits on reinfarction and rehospitalization rates
      especially in high risk subset of the patients. In addition to these medical
      benefits, an economical advantage of the invasive strategy is a reality by
      decreasing the hospital stay and reintervention incidence. Before intervention,
      optimal upstream medical treatment, selection of high risk patients and the
      lesions in which the intervention success expectation is low, is crucial for
      increasing the success of this strategy.

PMID- 16613773
TI  - [The use of other drugs apart from antithrombotic and antiplatelet agents for the
      treatment of non-ST-elevation acute coronary syndromes].
AB  - The purpose of this review is to summarize the established and evolving
      strategies used in the treatment of patients with unstable angina and non-ST
      segment elevation myocardial infarction. In this section we particularly
      emphasize the use of nitrates, beta-blockers, calcium channel blockers, statins,
      and angiotensin converting enzyme inhibitors.

PMID- 16613774
TI  - [Surgical treatment of non-ST-elevation acute coronary syndrome].
AB  - Patients with non-ST elevation acute coronary syndromes should be classified
      according to the risk characteristics. This classification is helpful to
      determine both the prognosis and the treatment strategy in early period. In high
      risk patients, early invasive strategy including coronary angiography and
      percutaneous coronary angioplasty/stenting or coronary artery by-pass graft
      surgery (CABG) revascularization is recommended. As a surgical method, off-pump
      or classical method with cardiopulmonary by-pass CABG can be preferred. In both
      methods, the aim should be the protection of myocardium and complete
      revascularization. Clinical features, age, co-morbidities, vascular anatomy,
      surgical experience should be considered for choosing the revascularization
      technique.

PMID- 16613775
TI  - Gap junctional communication does not contribute to the interaction between
      neutrophils and airway epithelial cells.
AB  - Cystic fibrosis (CF) is characterized by intense neutrophil migration into the
      airways. Increasing evidence indicates that interaction between neutrophils and
      airway epithelial cells contributes to the modulation of the inflammatory
      response. Blood neutrophils were reported to express connexins and form gap
      junctions with endothelial cells, thereby establishing gap junctional
      communication. We tested whether altered communication between human neutrophils
      and airway epithelial cells may contribute to the exaggerated inflammatory
      response observed in CF patients. Microinjections did not reveal dye coupling
      between activated blood neutrophils. By contrast, diffusion of calcein between
      neutrophils and airway epithelial cells of CF or non-CF origin was observed in
      transmigration and adhesion assays. This diffusion was prevented with probenicid,
      an inhibitor of ATP-dependent organic anion pumps, but not with gap junction
      blockers. Finally, RT-PCR failed to detect mRNAs for six connexins in blood
      neutrophils. These results suggest that gap junctional communication does not
      contribute to neutrophil-airway epithelial cell interaction.

PMID- 16613776
TI  - Administration of FGF-2 to the heart stimulates connexin-43 phosphorylation at
      protein kinase C target sites.
AB  - Fibroblast growth factor-2 (FGF-2) confers acute, preconditioning-like cardiac
      resistance to ischemic injury in a protein kinase C (PKC)-dependent fashion. One
      of the downstream targets of PKC is the gap junction protein connexin-43 (Cx43).
      We thus examined the effects of FGF-2 on Cx43 phosphorylation at specific PKC
      sites in the adult heart. Rat hearts perfused ex vivo for 20 min with an FGF-2
      containing solution displayed increased levels of phosphorylated 44-45 kDa Cx43,
      assessed by western blotting. In addition, FGF-2 significantly upregulated
      phosphorylation of the PKC target serines 262 and 368 on Cx43 at intercalated
      disks, assessed using phosphospecific antibodies in immunolocalization and
      western blotting assays. Our data show that FGF-2, administered by perfusion, can
      alter the phosphorylation status of Cx43 at cardiomyocyte intercalated disks, and
      suggest a link between phosphorylation of Cx43 at specific PKC sites and FGF-2
      cardioprotection.

PMID- 16613777
TI  - The antiarrhythmic peptide rotigaptide (ZP123) increases connexin 43 protein
      expression in neonatal rat ventricular cardiomyocytes.
AB  - Rotigaptide (formerly ZP123) is a novel antiarrhythmic peptide that prevents
      uncoupling of connexin 43 (Cx43)-mediated, gap junction communication during
      acute metabolic stress. Since rotigaptide's long-term effects on Cx43 are
      unknown, we studied its effect on Cx43 protein levels at 24 h in neonatal
      ventricular myocytes. As determined by Western blot analysis, rotigaptide
      produced a dose-dependent increase in Cx43 protein expression that reached a
      maximum level at 100 nM. Furthermore, 100 nM rotigaptide markedly increased Cx43
      immunoreactivity and Cx43-positive gap junctions as observed in
      immunocytochemical studies. Cycloheximide, an inhibitor of protein synthesis, was
      used to investigate rotigaptide's mechanism of action. Cycloheximide (10
      microg/ml) reduced Cx43 protein levels to 39% of vehicle (17 mM ethanol) whereas
      cotreatment of 10 microg/ml cycloheximide with 100 nM rotigaptide reduced Cx43
      protein levels to 56% of vehicle. Our findings suggest that rotigaptide's effect
      on Cx43 expression is partly due to increased biosynthesis.

PMID- 16613778
TI  - Local Ca2+ rise near store operated Ca2+ channels inhibits cell coupling during
      capacitative Ca2+ influx.
AB  - Using a new fluorescence imaging technique, LAMP, we recently reported that
      Ca(2+) influx through store operated Ca(2+) channels (SOCs) strongly inhibits
      cell coupling in primary human fibroblasts (HF) expressing Cx43. To understand
      the mechanism of inhibition, we studied the involvement of cytosolic pH (pH(i))
      and Ca(2+)([Ca(2+)](i)) in the process by using fluorescence imaging and ion
      clamping techniques. During the capacitative Ca(2+) influx, there was a modest
      decline of pH(i) measured by BCECF. Decreasing pH(i) below neutral using
      thioacetate had little effect by itself on cell coupling, and concomitant pH(i)
      drop with thioacetate and bulk [Ca(2+)(i) rise with ionomycin was much less
      effective in inhibiting cell coupling than Ca(2+) influx. Moreover, clamping
      pH(i) with a weak acid and a weak base during Ca(2+) influx largely suppressed
      bulk pH(i) drop, yet the inhibition of cell coupling was not affected. In
      contrast, buffering [Ca(2+)(i) with BAPTA, but not EGTA, efficiently prevented
      cell uncoupling by Ca(2+) influx. We concluded that local Ca(2+) elevation
      subjacent to the plasma membrane is the primary cause for closing Cx43 channels
      during capacitative Ca(2+) influx. To assess how Ca(2+) influx affects junctional
      coupling mediated by other types of connexins, we applied the LAMP assay to Hela
      cells expressing Cx26. Capacitative Ca(2+) influx also caused a strong reduction
      of cell coupling, suggesting that the inhibitory effect by Ca(2+) influx may be a
      more general phenomenon.

PMID- 16613779
TI  - Regulation of gap junction coupling through the neuronal connexin Cx35 by nitric
      oxide and cGMP.
AB  - Gap-junctional coupling among neurons is subject to regulation by a number of
      neurotransmitters including nitric oxide. We studied the mechanisms by which NO
      regulates coupling in cells expressing Cx35, a connexin expressed in neurons
      throughout the central nervous system. NO donors caused potent uncoupling of HeLa
      cells stably transfected with Cx35. This effect was mimicked by Bay 21-4272, an
      activator of guanylyl cyclase. A pharmacological analysis indicated that NO
      induced uncoupling involved both PKG-dependent and PKG-independent pathways. PKA
      was involved in both pathways, suggesting that PKG-dependent uncoupling may be
      indirect. In vitro, PKG phosphorylated Cx35 at three sites: Ser110, Ser276, and
      Ser289. A mutational analysis indicated that phosphorylation on Ser110 and
      Ser276, sites previously shown also to be phosphorylated by PKA, had a
      significant influence on regulation. Ser289 phosphorylation had very limited
      effects. We conclude that NO can regulate coupling through Cx35 and that
      regulation is indirect in HeLa cells.

PMID- 16613780
TI  - Spatiotemporal expression of connexin 39 and -43 during myoblast differentiation
      in cultured cells and in the mouse embryo.
AB  - Connexin39 (Cx39) and connexin43 (Cx43) are known to be expressed during
      development of skeletal muscles. Here we have compared the expression pattern of
      both connexins during differentiation of established C(2)C(12) mouse myoblasts
      and in the mouse embryo. Cx43 is highly abundant in undifferentiated myoblasts,
      but no Cx39 protein was detected in these cells. Upon differentiation into
      myotubes, Cx39 expression increased. The consecutive expression of these
      connexins was also observed in the mouse embryo. Cx39 and Cx43 were found in
      different plaques in accordance with the notion that Cx43 is exclusively
      expressed in myoblasts and Cx39 in myotubes. Thus, differentiating C(2)C(12)
      cells in culture can serve to study the involvement of gap junctions in
      myogenesis, since expression of corresponding Cx39 and Cx43 proteins appears to
      be very similar as in the mouse embryo.

PMID- 16613781
TI  - Cx37 and Cx43 localize to zona pellucida in mouse ovarian follicles.
AB  - In the ovarian follicle, granulosa cells adjacent to the oocyte extend processes
      through the zona pellucida matrix, and these projections establish gap junctions
      both with the oocyte and with neighboring transzonal projections. The identity of
      connexins contributing to gap junctions between transzonal projections has not
      been extensively studied. Here, we examined the expression pattern of Cx37 and
      Cx43 in mouse zona pellucida using multiple connexin-specific antibodies.
      Immunofluorescence staining revealed abundant Cx37 and Cx43 puncta within the
      zona pellucida of both preantral and antral follicles. Cx37 persisted in the zona
      pellucida of mature follicles up to 5 h after an ovulatory stimulus whereas Cx43
      was reduced in the zona pellucida by 3 h after an ovulatory stimulus. We suggest
      that in addition to its role in oocyte-granulosa cell communication, Cx37 could
      enable a distinct communication pathway between those granulosa cells that are in
      direct contact with the oocyte.

PMID- 16613782
TI  - Connexin over-expression differentially suppresses glioma growth and contributes
      to the bystander effect following HSV-thymidine kinase gene therapy.
AB  - Neoplastic transformation is frequently associated with a loss of gap junctional
      intercellular communication and reduced expression of connexins. The introduction
      of connexin genes into tumor cells reverses the proliferative characteristics of
      such cells. However, there is very little comparative information on the effects
      of different connexins on cancer cell growth. We hypothesized that Cx26, Cx32, or
      Cx43 would display differential growth suppression of C6 glioma cells and
      uniquely modulate the bystander effect following transduction of C6 cells with
      HSVtk followed by suicide gene therapy. The bystander phenomenon is the death of
      a greater number of tumor cells than are expressing the HSVtk gene, presumably
      due to the passage of toxic molecules through gap junction channels. To test this
      hypothesis, we used retroviral vectors to infect C6 glioma cells producing
      connexin-expressing and HSVtk-expressing cell lines. All three connexin
      expressing cell lines grew significantly slower than GFP-infected or native C6
      cells. Cx32 and Cx26 were significantly more effective at mediating the bystander
      effect in cocultures of C6-connexin cells with C6-HSVtk cells. These studies
      indicate that connexins have unique properties that contribute to their tumor
      suppressive function.

PMID- 16613783
TI  - Gap junctions mediate glucose transport between GLUT1-positive and -negative
      cells in the spiral limbus of the rat cochlea.
AB  - To elucidate the role of the spiral limbus in glucose transport in the cochlea,
      we analyzed the expression and localization of GLUT1, connexin26, connexin30, and
      occludin in the spiral limbus of the rat cochlea. GLUT1 and occludin were
      detected in blood vessels. GLUT1, connexin26, connexin30, and occludin were also
      expressed in fibrocytes just basal to the supralimbal lining cells. Connexin26
      and connexin30 were present among not only these GLUT1-positive fibrocytes but
      also GLUT1-negative fibrocytes. In vivo glucose imaging using 6-[N-(7-nitrobenz-2
      oxa-1,3-diazol-4-yl)amino]-6-deoxyglucose (6-NBDG, MW 342) together with Evans
      Blue Albumin (EBA, MW 68,000) showed that 6-NBDG was rapidly distributed
      throughout the spiral limbus, whereas EBA was localized only in the vessels.
      Moreover, the gap junctional uncoupler heptanol inhibited the distribution of 6
      NBDG. These findings suggest that gap junctions play an important role in glucose
      transport in the spiral limbus, i.e., that gap junctions mediate glucose
      transport from GLUT1-positive fibrocytes to GLUT1-negative fibrocytes in the
      spiral limbus.

PMID- 16613784
TI  - DE-cadherin, a core component of the adherens junction complex modifies
      subcellular localization of the Drosophila gap junction protein innexin2.
AB  - The Drosophila innexin multigene family of gap junction encoding proteins
      consists of eight family members whose function in epithelial morphogenesis is
      mostly unknown. We have recently shown that innexin2 plays a crucial role in the
      organization of embryonic epithelia. Innexin2 protein accumulates in the
      epidermis in the apico-lateral membrane domain and colocalizes with core proteins
      of adherens junctions, such as DE-cadherin and Armadillo, the ss -catenin
      homolog. Innexin2 localization is altered in both armadillo and DE-cadherin
      mutants Biochemical interaction studies point to a direct interaction of DE
      cadherin and Armadillo with innexin2 suggesting a close link between gap junction
      and adherens junction biogenesis. We have used the Drosophila Schneider cell
      tissue culture system to further study the interaction of innexin2 with DE
      cadherin. Our results provide evidence that DE-cadherin may be a key component to
      control trafficking, and localization of Innexin2 to the plasma membrane.

PMID- 16613787
TI  - Serum lipid levels at 28-32 weeks gestation and hypertensive disorders.
AB  - BACKGROUND: The etiology and pathogenesis of hypertensive disorders complicating
      pregnancy are poorly understood, and the definition of these disorders is
      controversial. METHODS: In a prospective study, 470 primigravida women between 28
      and 32 weeks of pregnancy were evaluated for serum levels of total cholesterol,
      low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and
      triglyceride. Afterward, they were observed for any symptoms of preeclampsia and
      gestational hypertension until 40 weeks of gestational age. We than compared the
      serum lipid levels among women with preeclampsia and gestational hypertension
      with those of matched women with normal pregnancies. RESULTS: The numbers of
      patients developing preeclampsia and gestational hypertension were 25 (5.3%) and
      32 (6.8%), respectively. At the beginning of the study, the mean values of serum
      triglyceride levels between women who later experienced preeclampsia or
      gestational hypertension and those who did not differed significantly (p <
      0.0001, p < 0.03). CONCLUSION: Although many cases of gestational hypertension
      represent latent essential hypertension based on the lipid levels, some of these
      women display true pregnancy-induced hypertension or nonproteinuric preeclampsia.

PMID- 16613785
TI  - Mechanical loading stimulates expression of connexin 43 in alveolar bone cells in
      the tooth movement model.
AB  - Bone osteoblasts and osteocytes express large amounts of connexin (Cx) 43, the
      component of gap junctions and hemichannels. Previous studies have shown that
      these channels play important roles in regulating biological functions in
      response to mechanical loading. Here, we characterized the distribution of mRNA
      and protein of Cx43 in mechanical loading model of tooth movement. The locations
      of bone formation and resorption have been well defined in this model, which
      provides unique experimental systems for better understanding of potential roles
      of Cx43 in bone formation and remodeling under mechanical stimulation. We found
      that mechanical loading increased Cx43 mRNA expression in osteoblasts and bone
      lining cells, but not in osteocytes, at both formation and resorption sites. Cx43
      protein, however, increased in both osteoblasts and osteocytes in response to
      loading. Interestingly, the upregulation of Cx43 protein by loading was even more
      pronounced in osteocytes compared to other bone cells, with an appearance of
      punctate staining on the cell body and dendritic process. Cx45 was reported to be
      expressed in several bone cell lines, but here we did not detect the Cx45 protein
      in the alveolar bone cells. These results further suggest the potential
      involvement of Cx43-forming gap junctions and hemichannels in the process of
      mechanically induced bone formation and resorption.

PMID- 16613789
TI  - Third nerve palsy and serous retinal detachment with preeclampsia.
AB  - Visual disturbances occur more frequently during preeclampsia than during
      pregnancy in general, but visual disturbances due to cranial nerve palsy are
      rare. We present the case of a 35-year-old preeclamptic woman with left third
      nerve palsy and left serous retinal detachment. The patient complained of visual
      disturbance and double vision soon after cesarean section. Left third nerve palsy
      and left serous retinal detachment were diagnosed by urgent ophthalmologic
      evaluation. Aneurysm and organic brain lesion were ruled out by diagnostic
      imaging. By 2 months postpartum, the visual disturbance had improved
      spontaneously.

PMID- 16613788
TI  - Study of association between hypertensive disorders of pregnancy and the human
      coagulation factor XI gene.
AB  - OBJECTIVE: Hypertensive disorders of pregnancy (HDP) are among the most common
      and serious complications of pregnancy. Persuasive evidence implicaties genetic
      factors in the genesis of HDP. The aim of the present study was to assess the
      association between single-nucleotide polymorphisms (SNPs) in the human
      coagulation factor XI (F11) gene and HDP, by conducting a haplotype-based case
      control study. METHODS: We chose 3 SNPs (rs925453, rs925451, and rs12500151) in
      the human F11 gene as genetic markers. We then conducted an association study
      with 77 HDP patients and 154 age-matched non-HDP subjects. RESULTS: The frequency
      of rs925453 genotypes significantly differed between the two groups. The
      frequency of the T-G-G haplotype was significantly higher in the HDP group than
      in the non-HDP group (p = 0.0002). CONCLUSIONS: The T allele of rs925453 and the
      T-G-G haplotype appear to be useful genetic markers of HDP.

PMID- 16613790
TI  - The activity of erythrocyte sodium-proton exchanger in women with pregnancy-
      induced hypertension.
AB  - BACKGROUND: Hypertension that develops after 20 gestational weeks and is defined
      as pregnancy-induced hypertension (PIH). The main cause of PIH is
      vasoconstriction and the thickening of vascular media, which decreases vascular
      capacity and increases peripheral resistance. One of the theories postulated to
      explain this phenomenon is that a transmembrane sodium transport disorder causes
      an increase in intracellular sodium concentration. In the latest literature,
      special attention is paid to the role of the increased intracellular sodium
      concentration in the pathogenesis of essential hypertension (EH). One of the best
      documented phenotypes for EH is the increased activity of the sodium-proton
      exchanger (NHE). The aim of this study was to assess if increased NHE activity
      could be the mechanism responsible for the development of PIH. SUBJECTS AND
      METHODS: The study included 30 women: 10 pregnant women with PIH after
      gestational week 30, 10 women with physiological pregnancy after 30 gestational
      weeks, and 10 healthy non-pregnant women. NHE activity was determined according
      to Orlov's method as amiloride-sensitive H(+) efflux from acid-loaded cells.
      RESULTS: The NHE activity in the group of women with PIH was significantly higher
      than that in women with physiological pregnancy: 10.09 +/- 1.65 vs. 6.81 +/- 2.3
      mmol/L RBC/h (p < 0.049) and in the group of non-pregnant women: 10.09 +/- 1.65
      vs. 7.56 +/- 1.66 mmol/L RBC/h (p < 0.029). Erythrocyte NHE activity did not
      differ in the group of women with physiological pregnancy and in the group of non
      pregnant women. CONCLUSION: These results seem to suggest that erythrocyte NHE
      activity is elevated in PIH pregnancies.

PMID- 16613792
TI  - Dynamics of neural populations: stability and synchrony.
AB  - A population formulation of neuronal activity is employed to study an excitatory
      network of (spiking) neurons receiving external input as well as recurrent
      feedback. At relatively low levels of feedback, the network exhibits time
      stationary asynchronous behavior. A stability analysis of this time stationary
      state leads to an analytical criterion for the critical gain at which time
      asynchronous behavior becomes unstable. At instability the dynamics can undergo a
      supercritical Hopf bifurcation and the population passes to a synchronous state.
      Under different conditions it can pass to synchrony through a subcritical Hopf
      bifurcation. And at high gain a network can reach a runaway state, in finite
      time, after which the network no longer supports bounded solutions. The
      introduction of time delayed feedback leads to a rich range of phenomena. For
      example, for a given external input, increasing gain produces transition from
      asynchrony, to synchrony, to asynchrony and finally can lead to divergence. Time
      delay is also shown to strongly mollify the amplitude of synchronous
      oscillations. Perhaps, of general importance, is the result that synchronous
      behavior can exist only for a narrow range of time delays, which range is an
      order of magnitude smaller than periods of oscillation.

PMID- 16613793
TI  - Excitability changes that complement Hebbian learning.
AB  - Experiments have shown that the intrinsic excitability of neurons is not
      constant, but varies with physiological stimulation and during various learning
      paradigms. We study a model of Hebbian synaptic plasticity which is supplemented
      with intrinsic excitability changes. The excitability changes transcend time
      delays and provide a memory trace. Periods of selective enhanced excitability can
      thus assist in forming associations between temporally separated events, such as
      occur in trace conditioning. We demonstrate that simple bidirectional networks
      with excitability changes can learn trace conditioning paradigms.

PMID- 16613794
TI  - Decoupling functional mechanisms of adaptive encoding.
AB  - In a natural setting, adaptive mechanisms constantly modulate the encoding
      properties of sensory neurons in response to changes in the external environment.
      Recent experiments have revealed that adaptation affects both the spatiotemporal
      integration properties and baseline membrane potential of sensory neurons.
      However, the precise functional role of adaptation remains an open question, due
      in part to contradictory experimental results. Here, we develop a framework to
      characterize adaptive encoding, including a cascade model with a time-varying
      receptive field (reflecting spatiotemporal integration properties) and offset
      (reflecting baseline membrane potential), and a recursive technique for tracking
      changes in the model parameters during a single stimulus/response trial.
      Simulated and experimental responses from retinal neurons are used to track
      adaptive changes in receptive field structure and offset during nonstationary
      stimulation. Due to the nonlinear nature of spiking neurons, the parameters of
      the receptive field and offset must be estimated simultaneously, or changes in
      the offset (or even in the statistical distribution of the stimulus) can mask,
      confound, or create the illusion of adaptive changes in the receptive field. Our
      analysis suggests that these confounding effects may be at the root of the
      inconsistency in the literature and shows that seemingly conflicting experimental
      results can be reconciled within our framework.

PMID- 16613795
TI  - Dopamine, prediction error and associative learning: a model-based account.
AB  - The notion of prediction error has established itself at the heart of formal
      models of animal learning and current hypotheses of dopamine function. Several
      interpretations of prediction error have been offered, including the model-free
      reinforcement learning method known as temporal difference learning (TD), and the
      important Rescorla-Wagner (RW) learning rule. Here, we present a model-based
      adaptation of these ideas that provides a good account of empirical data
      pertaining to dopamine neuron firing patterns and associative learning paradigms
      such as latent inhibition, Kamin blocking and overshadowing. Our departure from
      model-free reinforcement learning also offers: 1) a parsimonious distinction
      between tonic and phasic dopamine functions; 2) a potential generalization of the
      role of phasic dopamine from valence-dependent "reward" processing to valence
      independent "salience" processing; 3) an explanation for the selectivity of
      certain dopamine manipulations on motivation for distal rewards; and 4) a
      plausible link between formal notions of prediction error and accounts of
      disturbances of thought in schizophrenia (in which dopamine dysfunction is
      strongly implicated). The model distinguishes itself from existing accounts by
      offering novel predictions pertaining to the firing of dopamine neurons in
      various untested behavioral scenarios.

PMID- 16613796
TI  - V1 non-linear properties emerge from local-to-global non-linear ICA.
AB  - It has been argued that the aim of non-linearities in different visual and
      auditory mechanisms may be to remove the relations between the coefficients of
      the signal after global linear ICA-like stages. Specifically, in Schwartz and
      Simoncelli (2001), it was shown that masking effects are reproduced by fitting
      the parameters of a particular non-linearity in order to remove the dependencies
      between the energy of wavelet coefficients. In this work, we present a different
      result that supports the same efficient encoding hypothesis. However, this result
      is more general because, instead of assuming any specific functional form for the
      non-linearity, we show that by using an unconstrained approach, masking-like
      behavior emerges directly from natural images. This result is an additional
      indication that Barlow's efficient encoding hypothesis may explain not only the
      shape of receptive fields of V1 sensors but also their non-linear behavior.

PMID- 16613798
TI  - When a partner dies: lesbian widows.
AB  - Death of a life partner and the subsequent bereavement are profound experiences
      for an individual. By far, the majority of bereavement research reported is
      focused on heterosexual couples, primarily married and often in the later years
      of life. The purpose of this study was to describe the bereavement experiences of
      lesbians whose life partners have died. The study used a descriptive, qualitative
      design informed by feminist scholarship and phenomenology to access the depth of
      personal experiences, as well as internally interpreted meanings of those
      experiences, among lesbian widows.

PMID- 16613799
TI  - Telematic technologies in mental health caring: a web-based psychoeducational
      program for adolescent suicide survivors.
AB  - A significant other's completed suicide elicits complex physical, psychological,
      and social reactions in most suicide survivors. At present, mental health
      professionals and other caregivers have limited access to clear information and
      guidelines to meet the postvention needs of these individuals. Telematic
      technologies offer innovative and creative resources to address their needs by
      means of a web-based psychoeducational program. The development of a
      comprehensive web-based program that deals with the lived experiences of
      adolescent suicide survivors is described. Potential program users include
      adolescent suicide survivors, social supporters of suicide survivors, mental
      health professionals and survivor support groups.

PMID- 16613800
TI  - Talking theory, talking therapy: Emmy Gut and John Bowlby.
AB  - Emmy Gut was a psychotherapist who developed, in her later years, a unique theory
      distinguishing between "productive" and "unproductive" depression. Dr. John
      Bowlby was a leading psychoanalyst famous for his work on attachment theory.
      After the death of her second husband, Emmy contacted John because his work on
      mourning and grief spoke to her own depressed state. Although her views of the
      world and of her relationship with John were clearly coloured by bouts of
      depression, she was profoundly influenced by her personal, therapeutic, and
      intellectual involvement with him. Evidence of his influence is seen in the
      volumes of correspondence flowing between them beginning in 1971 and continuing
      until John's death in 1990. During that time, Emmy wrote more than 100-some very
      lengthy-letters to John. Much of her correspondence was devoted to discussions
      about their often ambiguous and conflicted therapeutic relationship. Through an
      analysis of attachment theory and the nature of the client-therapist alliance,
      this paper offers insights into the effects that imbalances in power,
      expectations, and shifting needs can play in the recovery process.

PMID- 16613801
TI  - Towards malecentric communication: sensitizing health professionals to the
      realities of male childhood sexual abuse survivors.
AB  - This article extends earlier reports of an ongoing qualitative inquiry on
      childhood sexual abuse survivors' experiences with health professionals. In this
      paper, we aim to enhance understanding of male survivors' experience. While male
      and female participants express similar anxieties and fears about their
      encounters with health professionals, there are gender-based differences related
      to the perceptions of victimhood and manhood; guilt and shame; homophobia;
      disclosure of abuse; and the expression of vulnerability. The implications of
      these differences for sensitive health care practice are analyzed within the
      context of gender relationships and the differential socialization of men.
      Malecentric communication is proposed as a method for addressing the specific
      experiences of male survivors in their encounters with health professionals.

PMID- 16613802
TI  - Using projective techniques in the evaluation of groups for children of
      rehabilitating drug addicts.
AB  - Evaluators and researchers often have to deal with situations in which
      conventional research tools are impossible to use, either because of the
      characteristics of a population or unclear research variables. This paper
      presents a technique that succeeds in overcoming this kind of problem--a
      projective technique, but one that differs from the usual approach to projective
      techniques. The approach presented here is a hermeneutic one that assumes an
      interpretive process. By means of an example, this paper presents the process of
      working with projective techniques and concludes with a discussion of this
      approach.

PMID- 16613803
TI  - The process of recovery: a tale of two men.
AB  - Recovery has been identified as a focus for mental health care. Recovery requires
      learning to live again after a life-altering acute event or during a chronic
      illness, mental or physical. By analyzing within-person change over time,
      utilizing multiple sources of evidence, two cases illustrated particular
      dimensions that influenced the recovery process after stroke, within a
      biopsychosocial framework. Restoration of the self, through co-occurring, dual
      processes of grief and reconstruction, appeared to be an essential dimension in
      the recovery process. Suggestions for integrating this concept into current adult
      clinical practice are congruent with current models of disease management of
      several chronic conditions.

PMID- 16613804
TI  - Nurses' tending instinct as a conduit for men's access to mental health
      counseling.
AB  - No article has been found melding the phenomenon of nurses' tending instinct and
      men's mental health counseling access. This theoretical article presents nurses'
      tending instinct as a viable rationale to support men in utilizing mental health
      counseling services. Nurses can be the conduit that assists men in accessing
      mental health counseling when the need arises. An amalgamation of related topics,
      including nurses' tending instinct, men's illness/injury/disease profile,
      psychological medicine, and counselor skills, were forged together to unify this
      innovative theoretical consideration. Implications for nursing practice also were
      explored.

PMID- 16613805
TI  - Appreciating what works: discovering and dreaming alongside people developing
      resilient services for young people requiring mental health services.
AB  - Within this paper we report on a study undertaken to identify resilient services
      for young people requiring mental health services in the United Kingdom. Whilst
      undertaking the study we faced issues related to determining what constitutes
      mental health services, and issues related to different disciplinary perspectives
      and discourses. These were set within an environment that was changing rapidly as
      new ways of working were being implemented. Data were collected via interviews
      and surveys. Nearly every participant felt that young people were not served
      well. However, the study focused on things that were working well and were being
      achieved.

PMID- 16613806
TI  - Identifying soil cleanup criteria for dioxins in urban residential soils: how
      have 20 years of research and risk assessment experience affected the analysis?
AB  - This article reviews the scientific evidence and methodologies that have been
      used to assess the risks posed by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      presents a probabilistic analysis for identifying virtually safe concentrations
      of TCDD toxicity equivalents (TEQ) in residential soils. Updated data
      distributions that consider state-of-the-science cancer and noncancer toxicity
      criteria, child soil ingestion and dermal uptake, bioavailability in soil, and
      residential exposure duration are incorporated. The probabilistic analysis shows
      that the most sensitive determinants of dose and risk are childhood soil
      ingestion, exposure duration, and the selected TCDD cancer potency factor. It
      also shows that the cancer risk at 1 per 100,000 predicted more conservative
      (lower) soil criteria values than did the noncancer hazard (e.g., developmental
      and reproductive effects). In this analysis, acceptable or tolerable soil dioxin
      concentrations (TCDD TEQ) ranged from 0.4 to 5.5 ppb at the 95th percentile for
      cancer potency factors from 9600 to 156,000 (mg/kg/d)(-1) with site-specific
      adjustments not included. Various possible soil guidelines based on cancer and
      noncancer risks are presented and discussed. In the main, the current toxicology,
      epidemiology, and exposure assessment data indicate that the historical 1 ppb TEQ
      soil guidance value remains a reasonable screening value for most residential
      sites. This analysis provides risk managers with a thorough and transparent
      methodology, as well as a comprehensive information base, for making informed
      decisions about selecting soil cleanup values for PCDD/Fs in urban residential
      settings.

PMID- 16613807
TI  - Human response to dioxin: aryl hydrocarbon receptor (AhR) molecular structure,
      function, and dose-response data for enzyme induction indicate an impaired human
      AhR.
AB  - The aryl hydrocarbon receptor (AhR) mediates nearly all studied adverse effects
      of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and many related compounds. Binding
      of TCDD or related ligands to AhR is the key initiating event in downstream
      biochemical responses. The binding affinity of AhR for TCDD is specific to
      species and strain, and studies of human AhR demonstrate binding affinities
      approximately an order of magnitude or more lower than those observed in the most
      sensitive laboratory strains and species. Molecular genetic studies confirmed
      that human AhR shares key mutations with the DBA mouse strain that result in an
      "impaired" AhR (with respect to TCDD binding and responsiveness). Despite a
      number of polymorphisms in human AhR, the key "DBA-type" mutations appear to be a
      constant feature of the human AhR, and no polymorphisms have been identified that
      compensate for the impaired binding function conferred by these mutations.
      Consistent with the impaired binding status of the human AhR, human cells have
      consistently required approximately 10-fold higher concentrations of TCDD in
      vitro than rodent cells to respond with enzyme induction. Recent studies of in
      vivo enzyme induction-related endpoints in human populations with moderately and
      highly increased TCDD body burdens detected no relationship between these
      endpoints and TCDD body burdens at body-burden levels up to 250 ng TEQ/kg body
      weight, or approximately 25 times above the upper range of current general
      population background body burdens, while marked elevations in enzyme activity
      were observed in persons with body burdens above 750 ng TEQ/kg. In contrast, the
      more sensitive laboratory rodent strains and species exposed to TCDD exhibit
      significant enzyme induction at body burdens below 50 ng/kg. These interspecies
      data on the most sensitive and best understood response to binding of TCDD and
      related compounds to the AhR are consistent with the binding affinity and
      molecular structure data and support the hypothesis that the human AhR is less
      functional than the AhR of the more sensitive laboratory animals at a molecular
      level. Quantitative risk assessments involving interspecies extrapolation from
      sensitive laboratory species and strains should take these fundamental
      differences into account when margins of exposure and safety factors are
      considered.

PMID- 16613808
TI  - Coexistent Anaplastic and Differentiated Thyroid Carcinoma.
AB  - The aim of the present study was to clarify the underlying molecules that might
      contribute to the highly aggressive behavior of anaplastic thyroid carcinoma. We
      selected 5 cases of anaplastic thyroid carcinoma that had a differentiated area
      to determine differences in the molecules of undifferentiated and differentiated
      cancer cells. We immunohistochemically examined the localization of nuclear
      antigen (Ki-67), proliferating cell nuclear antigen (PCNA), p53, apoptotic
      protease-activating factor-1 (Apaf-1), CD26, galectin-3, E-cadherin, and CD147.
      We found an increased Ki-67, PCNA, and p53 labeling indices; decreased levels of
      Apaf-1, CD26, galectin-3, and E-cadherin; and overexpression of CD147 in the
      undifferentiated area compared with the differentiated area. These findings
      indicate high proliferative properties, suppression of apoptosis, disruption of
      cell-cell interaction, and induction of matrix metalloproteinases in the
      undifferentiated areas. Thus the molecules examined might be useful for
      evaluating the aggressive nature of this tumor and the prognosis.

PMID- 16613809
TI  - Exercise and the stress system.
AB  - Exercise represents a physical stress that challenges homeostasis. In response to
      this stressor, autonomic nervous system and the hypothalamic-pituitary-adrenal
      axis are known to react and to participate in the maintenance of homeostasis.
      This includes elevation of cortisol and cathecholamines in plasma. However,
      sustained physical conditioning in highly trained athletes is associated with a
      decreased hypothalamic-pituitary-adrenal response to exercise. On the other hand,
      highly trained athletes exhibit a chronic mild hypercortisolism at baseline that
      may be an adaptive change to chronic exercise. In addition the proinflammatory
      cytokine IL-6 is also activated. Moreover, exercise stimulates the secretion of
      GH and prolactin, and may influence the type of immunity by stimulating TH2
      response profile. Besides, the stress of exercise inhibits the gonadal function,
      through the production of glucocorticoids and cathecholamines, as well as through
      activation of the CRH neurons. Nowadays, apart from the beneficial effects of
      exercise, there is increasing incidence of exercise-related short- and long- term
      consequences, especially concerning the female athlete that many authors describe
      as the so-called "exercise-related female reproductive dysfunction". These
      consequences include amenorrhea, infertility, eating disorders, osteoporosis,
      coronary heart disease and euthyroid "sick" syndrome. The mechanisms involved in
      the pathogenesis of the above disorders are discussed in this review.

PMID- 16613810
TI  - Obesity and renal disease: a possible role of leptin.
AB  - Obesity is one of the most frequently encountered medical problems of our time.
      Among the complications of this pathologic entity, renal disease is an important
      issue and its pathophysiologic mechanisms are a challenge for the physician,
      since a variety of etiologic factors are implicated in its genesis. For example,
      hypertension, hyperlipidemia and insulin resistance affect renal function, each
      one in a different way. Obesity seems to be a state in which kidneys demonstrate
      morphological and functional alterations, while hormonal and growth factors play
      a significant role. Among them, leptin, a recently discovered cytokine, has
      undergone extended investigation and has proven to be a factor that contributes
      to renal disease, mainly through mechanisms that involve activation of the TGF
      beta system resulting in glomerulopathy and related clinical symptoms.
      Experiments in animals have revealed interesting aspects as far as the role of
      leptin in kidney function. Understanding the underlying mechanisms of obesity
      related glomerulopathy may become a valuable aid in handling an obese patient
      with renal disease and associated problems.

PMID- 16613811
TI  - Intramuscular administration of ACTH1-24 vs. 24-hour blood sampling in the
      assessment of adrenocortical function.
AB  - The standard intravenous short Synacthen test (SSST) has long been accepted as
      one of the most reliable diagnostic tests of adrenocortical insufficiency.
      Intramuscular (i.m.) administration of ACTH obviates the need of venous
      cannulation and can be used as an alternative to the intravenous test.
      Nevertheless, reports of correlation between cortisol response to i.m. ACTH1-24
      and 24-hr average cortisol concentration are scarce. We studied this relation in
      64 nonobese healthy men. Blood samples for serial cortisol measurements were
      collected hourly over 24 hrs. The following day, blood samples were collected at
      baseline and at 30 and 60 min after intramuscular (i.m.) administration of 250
      microg of ACTH1-24. All healthy men reached 24-hr serum cortisol peak values
      (Cmax) between 0600 h and 1000 h. Following i.m. ACTH1-24, cortisol levels
      significantly increased at both 30 (C30ACTH) and 60 (C60ACTH) minutes, when
      compared to baseline values. C30ACTH and C60ACTH significantly correlated with
      Cmax and with the 24-hr time-integrated cortisol concentration (AUC0-24). Morning
      mean cortisol was calculated as the average of serum concentrations measured
      between 0600 h and 1000 h (C(av)6-10) and correlated very well with AUC0-24. In
      conclusion, we confirmed that i.m. administration of ACTH1-24, followed by a
      single blood sampling at 60 min for cortisol measurement represents a valid,
      convenient and cost- effective screening test of adrenal function.

PMID- 16613812
TI  - TSH and thyroid hormones concentrations in patients with hypothyroidism receiving
      replacement therapy with L-thyroxine alone or in combination with L
      triiodothyronine.
AB  - The aim of this study was to evaluate parameters of thyroid function in patients
      with primary hypothyroidism receiving either monotherapy with L-T4 or combination
      L-T4+L-T3. Fifty-eight women with primary hypothyroidism receiving L-T4 were
      enrolled in the study. The patients were randomised into two groups: Group 1
      (n=42) patients continued monotherapy with L-T4, and Group 2 (n=16) patients were
      switched to combined therapy with L-T4+L-T3 (25 microg L-T4 was replaced with
      12.5 microg L-T3). The final examination was carried out 6 months thereafter.
      There was also a third group of 20 healthy women (control group). Under
      monotherapy with L-T4, serum FT4 levels were higher (p < 0.05) and FT3 lower (p <
      0.05) than in the control group, while the monotherapy subgroup of patients with
      low-normal TSH had serum FT4 levels higher than in the control group (p < 0.05).
      Serum FT4 under combined therapy was significantly lower than in both control and
      monotherapy groups. FT3 levels did not differ between the two groups of combined
      and monotherapy subjects; the highest FT3 levels were in the control group. L-T4
      replacement therapy is associated with non-physiologically high FT4 and low FT3
      levels. Therapy with L-T3 once a day does not simulate the normal production of
      T3 by the thyroid.

PMID- 16613813
TI  - Reassessment of combined LT4 and LT3 treatment for hypothyroidism: the prospects
      for slow-release T3 preparations.

PMID- 16613814
TI  - Preoperative imaging and localization of small sized insulinoma with EUS-guided
      fine needle tattoing: a case report.
AB  - We report a case of an insulinoma that was not identified on either Computerized
      Tomography (CT) scan and Magnetic Resonance Imaging (MRI). Endoscopic
      ultrasonography (EUS) revealed a small insulinoma located at the body of the
      pancreas, which was histologically confirmed. The patient underwent a laparotomy
      but no tumour was identified either on palpation or with intra-operative
      ultrasound (IOUS). Subsequently, a further EUS was performed and after the tumour
      was identified was injected with blue dye. The patient then underwent a second
      exploratory laparotomy and a tumour at the posterior aspect of the pancreas close
      to the left side of the portal vein was identified and was successfully excised.
      Histology confirmed the presence of an endocrine tumour staining for chromogranin
      A and insulin. The patient had an uneventful postoperative recovery and has
      developed no further episodes of hypoglycemia 3 years after surgery.

PMID- 16613815
TI  - The ancient and medieval Greek writer's perceptions concerning the relationship
      between sexual characteristics and testicular volume.

PMID- 16613816
TI  - Data mining: a new technique in medical research.

PMID- 16613817
TI  - Obesity in childhood and adolescence: a review in the interface between adipocyte
      physiology and clinical challenges.
AB  - Body weight is regulated by a feedback loop in which peripheral signals report
      nutritional information to an integratory center in the brain. The cloning of the
      ob gene is consistent with this concept and suggests that body fat content in
      adult rodents is regulated by a negative feedback loop centered in the
      hypothalamus. In recent years a number of additional signaling molecules secreted
      by adipose tissue have been discovered. These hormones, named adipocytokines,
      include resistin, adiponectin, and visfatin. Among the adipocytokines,
      adiponectin is perhaps the most interesting compound for the clinician since low
      adiponectin serum levels have been found in obese subjects and in particular in
      insulin resistant subjects. The definition and diagnosis of obesity in children
      and adolescents are surprisingly difficult. The level of fatness at which
      morbidity increases is determined on an acturial basis. In children and
      adolescents the degree of body fat mass depends upon ethnic background , gender,
      developmental stage, and age. Treatment and prevention of obesity in childhood
      and adolescence are major challenges for today's health care providers and
      societies.

PMID- 16613818
TI  - Endocrine manifestations in DiGeorge and other microdeletion syndromes related to
      22q11.2.

PMID- 16613819
TI  - Thyroid carcinoma in children and adolescents: presentation, clinical course, and
      outcome of therapy in 23 children and adolescents in Northern Greece.
AB  - OBJECTIVE: To define clinical presentation, surgical complications, follow-up
      characteristics, and survival of 23 children and adolescents with thyroid
      carcinoma. DESIGN: Retrospective analysis of data of 23 children and adolescents
      with thyroid carcinoma cared for in the Theagenion Cancer Hospital, Thessaloniki.
      RESULTS: At the time of diagnosis cervical lymph node metastases were present in
      18 (78.2%), mediastinal in 2 (8.69%), and pulmonary in 3 patients (13%). Total
      thyroidectomy was performed in 21 patients, with lymph node dissection in 18 and
      subtotal thyroidectomy in 2. No significant post-operative complications were
      observed. Histological examination revealed differentiated thyroid carcinoma
      (DTC). Tumor was multifocal in 11 (47.8%) and bilateral in 7 subjects (63.6%).
      Thyroid capsule invasion, vascular invasion, soft tissue involvement, and
      parathyroid gland invasion was observed in 12 out of 23 patients (52.1%). All
      patients received thyroxine suppressive therapy and 21 of them additional therapy
      with radioactive iodine (131I). During follow-up (5.5 years), 6 out of the 23
      patients presented new metastases in the cervical and mediastinal lymph nodes,
      lungs, and bones. At last follow-up, 11 patients (47.8%) had residual disease but
      all were alive. CONCLUSIONS: Thyroid carcinoma in children and adolescents can be
      quite aggressive. When a young patient presents thyroid nodule or multinodular
      goiter or palpable lymph nodes, the existence of thyroid carcinoma must be
      seriously considered.

PMID- 16613820
TI  - The use of Data Mining in the categorization of patients with Azoospermia.
AB  - OBJECTIVE: Data Mining is a relatively new field of Medical Informatics. The aim
      of this study was to compare Data Mining diagnosis with clinical diagnosis by
      applying a Data Miner (DM) to a clinical dataset of infertile men with
      azoospermia. DESIGN: One hundred and forty-seven azoospermic men were clinically
      classified into four groups: a) obstructive azoospermia (n=63), b) non
      obstructive azoospermia (n=71), c) hypergonadotropic hypogonadism (n=2), and d)
      hypogonadotropic hypogonadism (n=11). The DM (IBM's DB2/Intelligent Miner for
      Data 6.1) was asked to reproduce a four-cluster model. RESULTS: DM formed four
      groups of patients: a) eugonadal men with normal testicular volume and normal FSH
      levels (n=86), b) eugonadal men with significantly reduced testicular volume
      (median 6.5 cm3) and very high FSH levels (n=29), c) eugonadal men with
      moderately reduced testicular volume (median 14.5 cm3) and raised FSH levels
      (n=20), and d) hypogonadal men (n=12). Overall DM concordance rate in hypogonadal
      men was 92%, in obstructive azoospermia 73%, and in non-obstructive azoospermia
      69%. CONCLUSIONS: Data Mining produces clinically meaningful results but
      different from those of the clinical diagnosis. It is possible that the use of
      large sets of structured and formalised data and continuous evaluation of DM
      results will generate a useful methodology for the Clinician.

PMID- 16613821
TI  - A unique case of a benign adrenocortical tumor with triple secretion of cortisol,
      androgens, and aldosterone: development of multiple sclerosis after surgical
      removal of the tumor.
AB  - We present a 39-year old female with a benign adrenal tumor characterized by
      autonomous secretion of cortisol, androgens, and aldosterone. The patient
      presented with a 4-year history of hypertension and severe hirsutism. Baseline
      investigations revealed elevated testosterone, androstendione, and 17OH
      progesterone with normal levels of dehydroepi androsterone sulfate. CT of the
      adrenals revealed a 2.5 x 3.0 cm tumor with characteristics of an adenoma on the
      left adrenal gland. Pelvic ultrasound was normal. Further investigations revealed
      suppressed basal ACTH levels, loss of diurnal rhythm of cortisol, and failure to
      suppress on low dose dexamethasone suppression test, suggesting autonomous
      cortisol secretion by the tumor. She had an exaggerated response of 17OH
      progesterone to ACTH, implying reduced 21-hydroxylase activity. An elevated
      plasma aldosterone concentration to plasma renin activity ratio was suggestive of
      hyperaldosteronism, which was confirmed by failure of aldosterone to suppress to
      a formal saline infusion test. Complete clinical and biochemical remission of the
      disease was observed after left adrenalectomy. Histology confirmed the presence
      of an adrenocortical adenoma. The patient developed multiple sclerosis 6 months
      after the operation. The flare-up of an autoimmune disease (multiple sclerosis)
      postoperatively could be coincidental or possibly related to the high
      normalization of the high cortisol levels acting as a precipitating factor.

PMID- 16613822
TI  - Ectopic thyroid tissue in the lower neck with a coexisting normally located
      multinodular goiter and brief literature review.
AB  - Ectopic thyroid tissue in the lower neck with a coexisting normally located
      multinodular goiter is a rare entity. We present a 27-year old asymptomatic woman
      with a recent history of a painless mass in the left side of her lower neck.
      Thyroid function tests were normal. An ultrasound of her neck showed a
      multinodular goiter and a 3.4 cm solid mass in the left lower cervical area.
      These findings were confirmed by an MRI scan of her neck. The Tc99m Pertechnetate
      scan showed the presence of a functioning area under the left lobe of the thyroid
      gland. The patient underwent surgery. The cervical mass was identified as a
      structure separate from the left lobe of the thyroid, without any attachments to
      the body of the gland and was uniformly resected. A subtotal thyroidectomy was
      also performed. The histology revealed that the separate structure represented
      ectopic thyroid tissue. The patient had an uneventful postoperative recovery,
      subsequent to which she was euthyroid and had normal calcium levels.

PMID- 16613823
TI  - Polycystic ovary syndrome. Revised diagnostic criteria and long-term health
      consequences.
AB  - The diagnostic criteria for polycystic ovary syndrome (PCOS) have recently been
      revised. The polycystic ovarian morphology has been introduced as part of the
      criteria and an international consensus has been achieved providing the basis for
      future research and collaboration. It is now accepted that polycystic ovary
      syndrome has important long-term health implications, including metabolic
      disorders and increased risk factors for cardiovascular disease. The overall risk
      of developing type 2 diabetes among women with PCOS was found to be increased 3-7
      times. Women with PCOS have increased levels of cardiovascular risk factors:
      insulin resistance, obesity, dyslipidaemia, hypertension and markers of abnormal
      vascular function. However, the level of risk for cardiovascular disease remains
      uncertain. The limited epidemiological data available to date have shown no
      increase in cardiovascular events although the incidence of cerebrovascular
      events was increased. The evidence for an increased risk for endometrial
      carcinoma among women with PCOS is limited. Long-term epidemiological studies of
      women with well defined PCOS are needed in order to assess the risk of long-term
      health consequences, to identify the subgroups among PCOS women who need to be
      targeted and to determine the timing and nature of measures for intervention and
      prevention.

PMID- 16613824
TI  - Growth hormone binding protein and acid labile subunit levels in the assessment
      of acromegaly treatment.
AB  - OBJECTIVE: Post-treatment monitoring of acromegalic patients is a matter of
      controversy, as discrepancies between GH and IGF-I levels have been reported. The
      aim of our study was to evaluate the role of acid-labile subunit (ALS), a
      component of the 150 kD IGF-I/IGFBP-3/ALS complex, and the growth hormone binding
      protein (GHBP) in the follow-up of patients with acromegaly after therapeutic
      intervention. DESIGN: Forty-one patients with acromegaly, 10 at the time of
      diagnosis and 31 post therapeutic intervention, were studied. Patients were
      evaluated by the determination of baseline (fasting) IGF-I, ALS and GHBP and of
      glucose and GH during OGTT. RESULTS: Significantly lower ALS and higher GHBP
      levels were detected in successfully treated acromegalics compared to patients
      before treatment (34.1+/-1.6 vs. 52.8+/-2 mg/L and 0.9+/-0.08 vs 0.4+/-0.1 ig/L,
      respectively P<0.05). Furthermore, no difference was noted in ALS and GHBP values
      between patients successfully treated with either somatostatin analogues or
      another type of treatment. CONCLUSIONS: a) Successfully treated acromegalic
      patients demonstrate lower ALS and higher GHBP levels than patients before
      treatment, and b) somatostatin analogue treatment does not have a direct effect
      on GHBP and ALS concentration in acromegaly. Studies in larger groups of patients
      are needed to disclose whether these alterations will be useful in the post
      treatment assessment of acromegalic patients.

PMID- 16613825
TI  - Effects of GH and IGF-I on the in vitro maturation of mouse oocytes.
AB  - OBJECTIVE: A number of hormones and growth factors have been reported to affect
      the in vitro maturation of oocytes. Their exact effects on follicular growth and
      oocyte maturation and the mechanisms involved are still unclear. In the present
      study, we have investigated the effects of Growth Hormone (GH) and Insulin-like
      Growth Factor 1 (IGF-1) on the in vitro maturation of mouse oocytes. DESIGN:
      Immature preovulatory oocytes without cumulus cells (denuded), were obtained from
      4- to 8-week old female mice and were cultured in Ham's F-10 medium. GH and IGF-1
      were added separately or in combination in gradually increasing concentrations in
      the culture media, while medium-only containing samples were employed as
      controls. Oocyte development was assessed daily for three days and maturation was
      considered to be completed when the first polar body appeared. RESULTS: In
      control samples, 44+/-3% (mean+/-SE) of denuded oocytes formed a polar body. The
      achieved maturation rate after the addition of either GH or IGF-1 or GH plus IGF
      1 was significantly higher than in controls. The highest maturation rates were
      achieved after the addition of 0.2 microg/ml GH (76%+/-5%), 50 ng/ml IGF-1 (69%+/
      5%) and a combination of 0.2 microg/ml GH plus 10 ng/ml IGF-1 (75%+/-5%).
      CONCLUSIONS: The data suggest that GH and IGF-1, alone or in combination, affect
      mouse oocyte maturation significantly. The lack of a synergistic effect on oocyte
      cultures when both hormones were added indicates that both hormones act through
      the same signaling pathway.

PMID- 16613826
TI  - Hypoparathyroidism in a patient presenting with severe myopathy and skin rash.
      Case report and review of the literature.
AB  - A 47-year old man with idiopathic hypoparathyroidism (IHP), presented as severe
      myopathy and skin rash is described. The serum muscle enzymes were increased.
      After treatment with calcium and vitamin D, the clinical condition improved, the
      skin rash gradually disappeared, and the muscle enzymes decreased and remained
      within the normal range thereafter.

PMID- 16613827
TI  - A case of a prolactinoma resistant to dopamine agonists.
AB  - Dopamine agonists are the drugs of choice in the treatment of prolactinomas, the
      most common type of pituitary adenomas. However, up to 25% of prolactinomas do
      not respond to these drugs and alternative treatments have to be considered. We
      describe a 37-year old female with a microprolactinoma who, although having
      received all available formulations of dopamine agonists over a period of 11
      years, did not respond either clinically--diminution of galactorrhea and
      restoration of her menstrual cycle--or hormonally through normalisation of the
      elevated prolactin levels. Throughout the same period, the size of the adenoma
      remained unchanged. While on high doses of dopamine agonists, the patient
      presented with side effects such as nausea, vomiting, orthostatic hypotension and
      tachycardia without any symptoms of psychosis. Therefore, either the dose of the
      dopamine agonists was not toxic enough for the mesolimbic dopaminergic pathway to
      be activated or the patient was dopamine-resistant in this pathway as well.

PMID- 16613828
TI  - Hypophosphataemic osteomalacia due to de Toni-Debre-Fanconi syndrome in a 19-year
      old girl.
AB  - Osteomalacia associated with adult onset Fanconi syndrome is thought to result
      from hypophosphataemia due to renal phosphate loss and relative 1,25
      dihydroxyvitamin D3 deficiency. In this disorder, the impaired renal phosphate
      uptake occurs as part of a generalized tubular defect in association with other
      features such as bicarbonuria, glycosuria and aminoaciduria. Fanconi syndrome is
      either hereditary--juvenile form--or is associated with various acquired or
      heritable diseases. In adults, the disease is similar to the juvenile form, but
      osteomalacia is a prominent feature. We report a sporadic, adult onset,
      hypophosphataemia in a 19-year old female patient who presented after puberty
      complaining of bone and joint pain and difficulty in walking following a minor
      fall. Radiological examination revealed numerous bilateral fractures of the ribs
      and pelvis while biochemical investigations showed combination of high phosphate
      clearance, low serum bicarbonate, glycosuria and glycinuria. Known causes of
      acquired renal tubular dysfunction were ruled out. The patient was diagnosed as
      having idiopathic Fanconi syndrome and started on vitamin D3 (Alfacalcidol 1
      mg/day) and oral phosphorus (Joulie Solution, 1.5 g/day), which led to resolution
      of symptoms and an increase in serum phosphate (from 0,54 to 0,71 mmol/l) within
      few months following the initiation of therapy. However, radiological re
      examination showed no signs of fracture healing.

PMID- 16613829
TI  - On the centenary of the term "hormone".

PMID- 16613830
TI  - Regulation of early lung morphogenesis: questions, facts and controversies.
AB  - During early respiratory system development, the foregut endoderm gives rise to
      the tracheal and lung cell progenitors. Through branching morphogenesis, and in
      coordination with vascular development, a tree-like structure of epithelial
      tubules forms and differentiates to produce the airways and alveoli. Recent
      studies have implicated the fibroblast growth factor, sonic hedgehog, bone
      morphogenetic protein, retinoic acid and Wnt signaling pathways, and various
      transcription factors in regulating the initial stages of lung development.
      However, the precise roles of these molecules and how they interact in the
      developing lung is subject to debate. Here, we review early stages in lung
      development and highlight questions and controversies regarding their molecular
      regulation.

PMID- 16613831
TI  - Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers.
AB  - Mouse embryos bearing hypomorphic and conditional null Fgf8 mutations have small
      and abnormally patterned telencephalons. We provide evidence that the hypoplasia
      results from decreased Foxg1 expression, reduced cell proliferation and increased
      cell death. In addition, alterations in the expression of Bmp4, Wnt8b, Nkx2.1 and
      Shh are associated with abnormal development of dorsal and ventral structures.
      Furthermore, nonlinear effects of Fgf8 gene dose on the expression of a subset of
      genes, including Bmp4 and Msx1, correlate with a holoprosencephaly phenotype and
      with the nonlinear expression of transcription factors that regulate neocortical
      patterning. These data suggest that Fgf8 functions to coordinate multiple
      patterning centers, and that modifications in the relative strength of FGF
      signaling can have profound effects on the relative size and nature of
      telencephalic subdivisions.

PMID- 16613832
TI  - Drosophila Eph receptor guides specific axon branches of mushroom body neurons.
AB  - The conserved Eph receptors and their Ephrin ligands regulate a number of
      developmental processes, including axon guidance. In contrast to the large
      vertebrate Eph/Ephrin family, Drosophila has a single Eph receptor and a single
      Ephrin ligand, both of which are expressed within the developing nervous system.
      Here, we show that Eph and Ephrin can act as a functional receptor-ligand pair in
      vivo. Surprisingly, and in contrast to previous results using RNA-interference
      techniques, embryos completely lacking Eph function show no obvious axon guidance
      defects. However, Eph/Ephrin signaling is required for proper development of the
      mushroom body. In wild type, mushroom body neurons bifurcate and extend distinct
      branches to different target areas. In Eph mutants, these neurons bifurcate
      normally, but in many cases the dorsal branch fails to project to its appropriate
      target area. Thus, Eph/Ephrin signaling acts to guide a subset of mushroom body
      branches to their correct synaptic targets.

PMID- 16613833
TI  - Sample size planning for developing classifiers using high-dimensional DNA
      microarray data.
AB  - Many gene expression studies attempt to develop a predictor of pre-defined
      diagnostic or prognostic classes. If the classes are similar biologically, then
      the number of genes that are differentially expressed between the classes is
      likely to be small compared to the total number of genes measured. This motivates
      a two-step process for predictor development, a subset of differentially
      expressed genes is selected for use in the predictor and then the predictor
      constructed from these. Both these steps will introduce variability into the
      resulting classifier, so both must be incorporated in sample size estimation. We
      introduce a methodology for sample size determination for prediction in the
      context of high-dimensional data that captures variability in both steps of
      predictor development. The methodology is based on a parametric probability
      model, but permits sample size computations to be carried out in a practical
      manner without extensive requirements for preliminary data. We find that many
      prediction problems do not require a large training set of arrays for classifier
      development.

PMID- 16613834
TI  - Are clusters found in one dataset present in another dataset?
AB  - In many microarray studies, a cluster defined on one dataset is sought in an
      independent dataset. If the cluster is found in the new dataset, the cluster is
      said to be "reproducible" and may be biologically significant. Classifying a new
      datum to a previously defined cluster can be seen as predicting which of the
      previously defined clusters is most similar to the new datum. If the new data
      classified to a cluster are similar, molecularly or clinically, to the data
      already present in the cluster, then the cluster is reproducible and the
      corresponding prediction accuracy is high. Here, we take advantage of the
      connection between reproducibility and prediction accuracy to develop a
      validation procedure for clusters found in datasets independent of the one in
      which they were characterized. We define a cluster quality measure called the "in
      group proportion" (IGP) and introduce a general procedure for individually
      validating clusters. Using simulations and real breast cancer datasets, the IGP
      is compared to four other popular cluster quality measures (homogeneity score,
      separation score, silhouette width, and weighted average discrepant pairs score).
      Moreover, simulations and the real breast cancer datasets are used to compare the
      four versions of the validation procedure which all use the IGP, but differ in
      the way in which the null distributions are generated. We find that the IGP is
      the best measure of prediction accuracy, and one version of the validation
      procedure is the more widely applicable than the other three. An implementation
      of this algorithm is in a package called "clusterRepro" available through The
      Comprehensive R Archive Network (http://cran.r-project.org).

PMID- 16613835
TI  - 7,12-dimethylbenz[a]anthracene interferes with the development of cultured mouse
      mandibular molars.
AB  - Clinical studies suggest that maternal smoking during pregnancy can reduce the
      crown size of the child's teeth. Delayed dental age compared with chronological
      age has also been reported in children whose parents smoke. Among the main
      components of tobacco smoke are nonhalogenated polycyclic aromatic hydrocarbons
      (PAHs), many of which are highly toxic. Humans are exposed to PAH compounds
      mainly via tobacco smoke and diet. The aim of our study was to investigate the
      effect of PAHs on tooth formation and the function of tooth-forming cells. We
      exposed mouse (NMRI) E18 mandibular first and second molar explants to 7,12
      dimethylbenz[a]anthracene (DMBA), a toxic PAH compound, in organ culture for 7 or
      12 days. DMBA concentrations used were 0.1, 0.5, 1, and 2 microM. The mesiodistal
      width of each first molar (12-day culture) was measured in stereomicroscopic
      images, and the teeth were analysed histologically. DMBA exposure significantly
      reduced the mesiodistal width of the first molars. DMBA impaired or delayed
      amelogenesis and dentinogenesis in both molars at the lowest concentration of 0.1
      microM. DMBA affected enamel formation more severely than dentin formation and
      occasionally prevented amelogenesis completely. Elongation and polarization of
      ameloblasts were impaired, and blood vessel architecture of the dental papilla
      (future pulp) was altered. Cusps were thin and sharp. In line with the finding
      that maternal smoking during pregnancy has an adverse effect on child's tooth
      development, this study shows the toxic influence of PAHs on tooth development in
      vitro.

PMID- 16613836
TI  - Differential sensitivity of rat kidney and liver to fumonisin toxicity: organ
      specific differences in toxin accumulation and sphingoid base metabolism.
AB  - Fumonisins (FBs) are mycotoxins in maize and are inhibitors of ceramide synthase
      (CS), the most likely proximate cause of FB toxicity. In liver and kidney, the
      primary target organs in FB-fed rats, inhibition of CS results in a marked
      increase in the ceramide precursor sphinganine (Sa). This study was conducted to
      investigate the differential time- and dose-dependent changes in Sa, sphingosine
      (So), sphinganine 1-phosphate (Sa-1-P), and sphingosine 1-phosphate (So-1-P) in
      kidney, liver, serum, and heart of male Sprague-Dawley rats (3-4 weeks old) fed
      diets containing 1.1, 13.5, and 88.6 mug/g of total FB for 10 days. The tissues
      were microscopically examined for the presence and severity of lesions consistent
      with FB exposure. There was a time- and dose-dependent increase in Sa in both
      liver and kidney, which was closely correlated with the tissue concentration of
      fumonisin B(1) (FB(1)) and histopathologic findings. However, the Sa alone
      greatly underestimated the degree of disruption of sphingolipid metabolism since
      accumulated Sa and So were quickly metabolized to Sa-1-P and So-1-P as evidenced
      by large increases in these metabolites in kidney but not in liver. The
      concentration of FB(1) in liver and kidney that first elicited an increase in Sa
      was similar in both tissues, however, over time, the kidney accumulated
      significantly more FB(1) (10x) and total Sa (Sa plus Sa-1-P) compared to liver.
      Thus, the relative sensitivity of male Sprague-Dawley rat kidney and liver is
      most likely a consequence of differences in the mechanisms responsible for both
      FB(1) uptake/clearance and Sa metabolism.

PMID- 16613837
TI  - Correlating nanoscale titania structure with toxicity: a cytotoxicity and
      inflammatory response study with human dermal fibroblasts and human lung
      epithelial cells.
AB  - Nanocrystalline titanium dioxide (nano-TiO(2)) is an important material used in
      commerce today. When designed appropriately it can generate reactive species (RS)
      quite efficiently, particularly under ultraviolet (UV) illumination; this feature
      is exploited in applications ranging from self-cleaning glass to low-cost solar
      cells. In this study, we characterize the toxicity of this important class of
      nanomaterials under ambient (e.g., no significant light illumination) conditions
      in cell culture. Only at relatively high concentrations (100 microg/ml) of
      nanoscale titania did we observe cytotoxicity and inflammation; these cellular
      responses exhibited classic dose-response behavior, and the effects increased
      with time of exposure. The extent to which nanoscale titania affected cellular
      behavior was not dependent on sample surface area in this study; smaller
      nanoparticlulate materials had effects comparable to larger nanoparticle
      materials. What did correlate strongly to cytotoxicity, however, was the phase
      composition of the nanoscale titania. Anatase TiO(2), for example, was 100 times
      more toxic than an equivalent sample of rutile TiO(2). The most cytotoxic
      nanoparticle samples were also the most effective at generating reactive oxygen
      species; ex vivo RS species generation under UV illumination correlated well with
      the observed biological response. These data suggest that nano-TiO(2) samples
      optimized for RS production in photocatalysis are also more likely to generate
      damaging RS species in cell culture. The result highlights the important role
      that ex vivo measures of RS production can play in developing screens for
      cytotoxicity.

PMID- 16613838
TI  - Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL)-mediated apoptosis through CHOP-independent DR5 upregulation.
AB  - Death receptor DR5 (DR5/TRAIL-R2) is an apoptosis-inducing membrane receptor for
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In this study,
      we showed that curcumin, a plant product containing the phenolic phytochemical,
      is a potent enhancer of TRAIL-induced apoptosis through upregulation of DR5
      expression. Both treatment with DR5/Fc chimeric protein and silencing of DR5
      expression using small interfering RNA (siRNA) attenuated curcumin plus TRAIL
      induced apoptosis, showing that the critical role of DR5 in this cell death.
      Curcumin also induced the expression of a potential pro-apoptotic gene, C/EBP
      homologous protein (CHOP), both at its mRNA and protein levels. However,
      suppression of CHOP expression by small interfering RNA did not abrogate the
      curcumin-mediated induction of DR5 and the cell death induced by curcumin plus
      TRAIL, demonstrating that CHOP is not involved in curcumin-induced DR5
      upregulation. Taken together, the present study demonstrates that curcumin
      enhances TRAIL-induced apoptosis by CHOP-independent upregulation of DR5.

PMID- 16613839
TI  - Ras mutation promotes p53 activation and apoptosis of skin keratinocytes.
AB  - Previous studies in our laboratory demonstrated that 7,12
      dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA)
      treatment induced apoptosis and mitochondrial translocation of the tumor
      suppressor p53 in a mouse skin carcinogenesis model, suggesting that oncogenic
      versus cell death signaling involve a common mediator. Mutational activation of
      oncogenic Ras is an early event and has been demonstrated to play a critical role
      in skin carcinogenesis. A malignant skin keratinocyte cell line (308), which
      carries a H-ras mutation at codon 61, showed elevated p53 levels, increased
      caspase 3 activity and enhanced apoptosis after TPA treatment. In contrast, the
      non-malignant counterpart (C50) showed undetectable levels of p53 and less
      apoptosis than 308 cells similarly treated. Inhibition of NADPH-oxidase (NOX) by
      diphenyleneiodonium suppressed p53 activation and apoptosis in 308 cells, linking
      Ras mutation to NOX-induced p53 activation, which was further supported by the
      finding that siRNA to Rac1 inhibited p53 activation after TPA treatment.
      Application of DPI to DMBA-initiated skin tissue significantly blocked TPA
      mediated increased p53 levels and reduced apoptosis in skin epidermal tissues.
      Taken together, our results suggest that NOX bridges oncogenic activation and p53
      mitochondrial translocation to apoptosis in the multistage chemical-induced skin
      carcinogenesis model.

PMID- 16613840
TI  - Human gene profiling in response to the active protein kinase, interferon-induced
      serine/threonine protein kinase (PKR), in infected cells. Involvement of the
      transcription factor ATF-3 IN PKR-induced apoptosis.
AB  - The interferon-induced serine/threonine protein kinase (PKR) has an essential
      role in cell survival and cell death after viral infection and under stress
      conditions, but the host genes involved in these processes are not well defined.
      We used human cDNA microarrays to identify, in infected cells, genes
      differentially expressed after PKR expression and analyzed the requirement of
      catalytic activity of the enzyme. To express PKR, we used vaccinia virus (VV)
      recombinants producing wild type PKR (VV-PKR) and the catalytically inactive
      mutant K296R (VV-PKR-K296R). Most regulated genes were classified according to
      biological function, including apoptosis, stress, defense, and immune response.
      Transcriptional changes detected by microarray analysis were confirmed for
      selected genes by quantitative real time reverse transcription PCR. A total of
      111 genes were regulated specifically by PKR catalytic activity. Of these, 97
      were up-regulated, and 14 were down-regulated. The ATF-3 transcription factor,
      involved in stress-induced beta-cell apoptosis, was up-regulated. Activation of
      endogenous PKR with a VV mutant lacking the viral protein E3L (VVDeltaE3L), a PKR
      inhibitor, triggered an increase in ATF-3 expression that was not observed in
      PKR(-/-) cells. Using null cells for ATF-3 and for the p65 subunit of NF-kappaB,
      we showed that induction of apoptosis by PKR at late times of infection was
      dependent on ATF-3 expression and regulated by NF-kappaB activation. Here, we
      identified human genes selectively induced by expression of active PKR in
      infected cells and linked ATF-3 to a novel mechanism used by PKR to induce
      apoptosis.

PMID- 16613841
TI  - Characterization of a novel protein kinase D: Caenorhabditis elegans DKF-1 is
      activated by translocation-phosphorylation and regulates movement and growth in
      vivo.
AB  - Protein kinase D (PKD) isoforms are protein kinase C (PKC) effectors in
      diacylglycerol (DAG)-regulated signaling pathways. Key physiological processes
      are placed under DAG control by the distinctive substrate specificity and
      intracellular distribution of PKDs. Comprehension of the roles of PKDs in
      homeostasis and signal transduction requires further knowledge of regulatory
      interplay among PKD and PKC isoforms, analysis of PKC-independent PKD activation,
      and characterization of functions controlled by PKDs in vivo. Caenorhabditis
      elegans and mammals share conserved signaling mechanisms, molecules, and pathways
      Thus, characterization of the C. elegans PKDs could yield insights into
      regulation and functions that apply to all eukaryotic PKDs. C. elegans DKF-1 (D
      kinase family-1) contains tandem DAG binding (C1) modules, a PH (pleckstrin
      homology) domain, and a Ser/Thr protein kinase segment, which are homologous with
      domains in classical PKDs. DKF-1 and PKDs have similar substrate specificities.
      Phorbol 12-myristate 13-acetate (PMA) switches on DKF-1 catalytic activity in
      situ by promoting phosphorylation of a single amino acid Thr(588) in the
      activation loop. DKF-1 phosphorylation and activation are unaffected when PKC
      activity is eliminated by inhibitors. Both phosphorylation and kinase activity of
      DKF-1 are extinguished by substituting Ala for Thr(588) or Gln for Lys(455)
      ("kinase dead") or incubating with protein phosphatase 2C. Thus, DKF-1 is a PMA
      activated, PKC-independent D kinase. In vivo, dkf-1 gene promoter activity is
      evident in neurons. Both dkf-1 gene disruption (null phenotype) and RNA
      interference-mediated depletion of DKF-1 protein cause lower body paralysis.
      Targeted DKF-1 expression corrected this locomotory defect in dkf-1 null animals.
      Supraphysiological expression of DKF-1 limited C. elegans growth to approximately
      60% of normal length.

PMID- 16613843
TI  - The role of calmodulin recruitment in Ca2+ stimulation of adenylyl cyclase type
      8.
AB  - Ca2+ stimulation of adenylyl cyclase type 8 (AC8) is mediated by calmodulin
      (CaM). An earlier study identified two CaM binding sites in AC8; one that was
      apparently not essential for AC8 activity, located at the N terminus, and a
      second site that was critical for Ca2+ stimulation, found at the C terminus (Gu,
      C., and Cooper, D. M. F. (1999) J. Biol. Chem. 274, 8012-8021). This study
      explores the role of these two CaM binding domains and their interaction in
      regulating AC8 activity, employing binding and functional studies with mutant CaM
      and modified AC8 species. We report that the N-terminal CaM binding domain of AC8
      has a role in recruiting CaM and that this recruitment is essential to permit
      stimulation by Ca2+ in vivo. Using Ca2+-insensitive mutants of CaM, we found that
      partially liganded CaM can bind to AC8, but only fully liganded Ca2+/CaM can
      stimulate AC8 activity. Moreover, partially liganded CaM inhibited AC8 activity
      in vivo. The results indicate that CaM pre-associates with the N terminus of AC8,
      and we suggest that this recruited CaM is used by the C terminus of AC8 to
      mediate Ca2+ stimulation.

PMID- 16613842
TI  - Conserved domains subserve novel mechanisms and functions in DKF-1, a
      Caenorhabditis elegans protein kinase D.
AB  - Protein kinase D (PKD) isoforms are effectors in signaling pathways controlled by
      diacylglycerol. PKDs contain conserved diacylglycerol binding (C1a, C1b),
      pleckstrin homology (PH), and Ser/Thr kinase domains. However, the properties of
      conserved domains may vary within the context of distinct PKD polypeptides. Such
      functional/structural malleability (plasticity) was explored by studying
      Caenorhabditis elegans D kinase family-1 (DKF-1), a PKD that governs locomotion
      in vivo. Phorbol ester binding with C1b alone activates classical PKDs by
      relieving C1-mediated inhibition. In contrast, C1a avidly ligated phorbol 12
      myristate 13-acetate (PMA) and anchored DKF-1 at the plasma membrane. C1b bound
      PMA (moderate affinity) and cooperated with C1a in targeting DKF-1 to membranes.
      Mutations at a "Pro(11)" position in C1 domains were inactivating; kinase
      activity was minimal at PMA concentrations that stimulated wild type DKF-1
      approximately 10-fold. DKF-1 mutants exhibited unchanged, maximum kinase activity
      after cells were incubated with high PMA concentrations. Titration in situ
      revealed that translocation and activation of wild type and mutant DKF-1 were
      tightly and quantitatively linked at all PMA concentrations. Thus, C1 domains
      positively regulated phosphotransferase activity by docking DKF-1 with pools of
      activating lipid. A PH domain inhibits kinase activity in classical PKDs. The DKF
      1 PH module neither inhibited catalytic activity nor bound phosphoinositides.
      Consequently, the PH module is an obligatory, positive regulator of DKF-1
      activity that is compromised by mutation of Lys(298) or Trp(396). Phosphorylation
      of Thr(588) switched on DKF-1 kinase activity. Persistent phosphorylation of
      Thr(588) (activation loop) promoted ubiquitinylation and proteasome-mediated
      degradation of DKF-1. Each DKF-1 domain displayed novel properties indicative of
      functional malleability (plasticity).

PMID- 16613844
TI  - Protein-tyrosine phosphatase (PTP) wedge domain peptides: a novel approach for
      inhibition of PTP function and augmentation of protein-tyrosine kinase function.
AB  - Inhibition of protein-tyrosine phosphatases (PTPs) counterbalancing protein
      tyrosine kinases (PTKs) offers a strategy for augmenting PTK actions.
      Conservation of PTP catalytic sites limits development of specific PTP
      inhibitors. A number of receptor PTPs, including the leukocyte common antigen
      related (LAR) receptor and PTPmu, contain a wedge-shaped helix-loop-helix located
      near the first catalytic domain. Helix-loop-helix domains in other proteins
      demonstrate homophilic binding and inhibit function; therefore, we tested the
      hypothesis that LAR wedge domain peptides would exhibit homophilic binding, bind
      to LAR, and inhibit LAR function. Fluorescent beads coated with LAR or PTPmu
      wedge peptides demonstrated PTP-specific homophilic binding, and LAR wedge
      peptide-coated beads precipitated LAR protein. Administration of LAR wedge Tat
      peptide to PC12 cells resulted in increased proliferation, decreased cell death,
      increased neurite outgrowth, and augmented Trk PTK-mediated responses to nerve
      growth factor (NGF), a phenotype matching that found in PC12 cells with reduced
      LAR levels. PTPmu wedge Tat peptide had no effect on PC12 cells but blocked the
      PTPmu-dependent phenotype of neurite outgrowth of retinal ganglion neurons on a
      PTPmu substrate, whereas LAR wedge peptide had no effect. The survival- and
      neurite-promoting effect of the LAR wedge peptide was blocked by the Trk
      inhibitor K252a, and reciprocal co-immunoprecipitation demonstrated LAR/TrkA
      association. The addition of LAR wedge peptide inhibited LAR co
      immunoprecipitation with TrkA, augmented NGF-induced activation of TrkA, ERK, and
      AKT, and in the absence of exogenous NGF, induced activation of TrkA, ERK, and
      AKT. PTP wedge domain peptides provide a unique PTP inhibition strategy and offer
      a novel approach for augmenting PTK function.

PMID- 16613845
TI  - Conformational features of a natural break in the type IV collagen Gly-X-Y
      repeat.
AB  - Fibrillar collagens have an absolute requirement for Gly as every 3rd residue,
      whereas breaks in the Gly-X-Y repeating pattern are found normally in the triple
      helix domains of non-fibrillar collagens, such as type IV collagen in basement
      membranes. In this study, a model 30-mer peptide is designed to include the
      interruption GPOGAAVMGPOGPO found in the alpha5 chain of type IV collagen. The
      GAAVM peptide forms a stable triple helix, with Tm= 29 degrees C. When compared
      with a control peptide with Gly as every 3rd residue, the GAAVM peptide has a
      marked decrease in the 225 nm maximum of its CD spectrum and a 10 degrees C drop
      in stability. A 50% decrease in calorimetric enthalpy is observed, which may
      result from disruption of ordered water structure anchored by regularly placed
      backbone carbonyls. NMR studies on specific 15N-labeled residues within the GAAVM
      peptide indicate a normal triple helical structure for Gly-Pro-Hyp residues
      flanking the break. The sequence within the break is not disordered but shows
      altered hydrogen exchange rates and an abnormal Val chemical shift. It was
      previously reported that a peptide designed to model a similar kind of
      interruption in the peptide (Pro-Hyp-Gly)10, (GPOGPOPOGPO), is unable to form a
      stable triple helix, and replacement of GAA by GPO or VM by PO within the GAAVM
      break decreases the stability. Thus, rigid imino acids are unfavorable within a
      break, despite their favorable stabilization of the triple helix itself. These
      results suggest some non-random structure typical of this category of breaks in
      the Gly-X-Y repeat of the triple helix.

PMID- 16613846
TI  - 14-3-3 isoforms are induced by aldosterone and participate in its regulation of
      epithelial sodium channels.
AB  - Aldosterone increases sodium absorption across renal collecting duct cells
      primarily by increasing the apical membrane expression of ENaC, the sodium entry
      channel. Nedd4-2, a ubiquitin-protein isopeptide ligase, tags ENaC with ubiquitin
      for internalization and degradation, but when it is phosphorylated by the
      aldosterone-induced kinase, SGK1, Nedd4-2 is inhibited and apical ENaC density
      and sodium absorption increase. We evaluated the hypothesis that 14-3-3 proteins
      participate in the aldosterone-mediated regulation of ENaC by associating with
      phosphorylated Nedd4-2. Mouse cortical collecting duct (mCCD) epithelia cultured
      on filters expressed several 14-3-3 isoforms; this study focused on an isoform
      whose expression was induced 3-fold by aldosterone, 14-3-3beta. In polarized mCCD
      epithelia, aldosterone elicited significant, time-dependent increases in the
      expression of alpha-ENaC, SGK1, phospho-Nedd4-2, and 14-3-3beta without altering
      total Nedd4-2. Aldosterone decreased the interaction of alpha-ENaC with Nedd4-2,
      and with similar kinetics increased the association of 14-3-3beta with phospho
      Nedd4-2. Short interfering RNA-induced knockdown of 14-3-3beta blunted the
      aldosterone-induced increase in alpha-ENaC expression, returned alpha-ENaC-Nedd4
      2 binding toward prealdosterone levels, and blocked the aldosterone-stimulated
      increase in transepithelial sodium transport. Incubation of cell extracts with a
      selective phospho-Nedd4-2 antibody blocked the aldosterone-induced association of
      14-3-3beta with Nedd4-2, implicating SGK1 phosphorylation at Ser-328 as the
      primary site of 14-3-3beta binding. Our studies show that aldosterone increases
      the expression of 14-3-3beta, which interacts with phospho-Nedd4-2 to block its
      interaction with ENaC, thus enhancing sodium absorption by increasing apical
      membrane ENaC density.

PMID- 16613847
TI  - Nrf2 negatively regulates osteoblast differentiation via interfering with Runx2
      dependent transcriptional activation.
AB  - Nrf2 (nuclear factor E2 p45-related factor 2) is believed to be a transcription
      factor essential for the regulation of many detoxifying and antioxidative genes
      in different tissues. In the present study, we investigated the role of Nrf2 in
      the regulation of osteoblastic differentiation. nrf2 mRNA expression was
      significantly up-regulated in femur isolated from ovariectomized mice, whereas in
      situ hybridization analysis revealed that up-regulation of nrf2 mRNA was mainly
      found in osteoblasts attached on cancellous bone in femur of ovariectomized mice.
      Expression of Nrf2 protein was also seen in osteoblasts in neonatal mouse tibia
      and calvaria. In osteoblastic MC3T3-E1 cells stably transfected with nrf2
      expression vector, significant inhibition was seen in the maturation-dependent
      increase in alkaline phosphatase activity as well as the mineralized matrix
      formation. Stable overexpression of nrf2 significantly impaired Runx2 (runt
      related transcription factor 2)-dependent stimulation of osteocalcin promoter
      activity and recruitment of Runx2 on osteocalcin promoter without affecting the
      expression of runx2 mRNA. Coimmunoprecipitation and mammalian two-hybrid assay
      revealed a physical interaction between Runx2 and Nrf2, whereas cellular
      distribution of endogenous Runx2 was not apparently changed by nrf2
      overexpression in MC3T3-E1 cells. Alternatively, Nrf2 bound to antioxidant
      responsive element-like-2 sequence of osteocalcin promoter. The inhibition by
      nrf2 on runx2-dependent osteocalcin promoter activity was partially prevented by
      the introduction of reporter of deletion mutant for ARE-like-2 sequence of
      osteocalcin promoter. These data suggest that Nrf2 may negatively regulate
      cellular differentiation through inhibition of the Runx2-dependent
      transcriptional activity in osteoblasts.

PMID- 16613848
TI  - RANKL stimulates inducible nitric-oxide synthase expression and nitric oxide
      production in developing osteoclasts. An autocrine negative feedback mechanism
      triggered by RANKL-induced interferon-beta via NF-kappaB that restrains
      osteoclastogenesis and bone resorption.
AB  - Nitric oxide (NO) is a multifunctional signaling molecule and a key
      vasculoprotective and potential osteoprotective factor. NO regulates normal bone
      remodeling and pathological bone loss in part through affecting the recruitment,
      formation, and activity of bone-resorbing osteoclasts. Using murine RAW 264.7 and
      primary bone marrow cells or osteoclasts formed from them by receptor activator
      of NF-kappaB ligand (RANKL) differentiation, we found that inducible nitric-oxide
      synthase (iNOS) expression and NO generation were stimulated by interferon (IFN)
      gamma or lipopolysaccharide, but not by interleukin-1 or tumor necrosis factor
      alpha. Surprisingly, iNOS expression and NO release were also triggered by RANKL.
      This response was time- and dose-dependent, required NF-kappaB activation and new
      protein synthesis, and was specifically blocked by the RANKL decoy receptor
      osteoprotegerin. Preventing RANKL-induced NO (via iNOS-selective inhibition or
      use of marrow cells from iNOS-/- mice) increased osteoclast formation and bone
      pit resorption, indicating that such NO normally restrains RANKL-mediated
      osteoclastogenesis. Additional studies suggested that RANKL-induced NO inhibition
      of osteoclast formation does not occur via NO activation of a cGMP pathway.
      Because IFN-beta is also a RANKL-induced autocrine negative feedback inhibitor
      that limits osteoclastogenesis, we investigated whether IFN-beta is involved in
      this novel RANKL/iNOS/NO autoregulatory pathway. IFN-beta was induced by RANKL
      and stimulated iNOS expression and NO release, and a neutralizing antibody to IFN
      beta inhibited iNOS/NO elevation in response to RANKL, thereby enhancing
      osteoclast formation. Thus, RANKL-induced IFN-beta triggers iNOS/NO as an
      important negative feedback signal during osteoclastogenesis. Specifically
      targeting this novel autoregulatory pathway may provide new therapeutic
      approaches to combat various osteolytic bone diseases.

PMID- 16613849
TI  - The C5 domain of the collagen VI alpha3(VI) chain is critical for extracellular
      microfibril formation and is present in the extracellular matrix of cultured
      cells.
AB  - Collagen VI, a microfibrillar protein found in virtually all connective tissues,
      is composed of three distinct subunits, alpha1(VI), alpha2(VI), and alpha3(VI),
      which associate intracellularly to form triple helical heterotrimeric monomers
      then dimers and tetramers. The secreted tetramers associate end-to-end to form
      beaded microfibrils. Although the basic steps in assembly and the structure of
      the tetramers and microfibrils are well defined, details of the interacting
      protein domains involved in assembly are still poorly understood. To explore the
      role of the C-terminal globular regions in assembly, alpha3(VI) cDNA expression
      constructs with C-terminal truncations were stably transfected into SaOS-2 cells.
      Control alpha3(VI) N6-C5 chains with an intact C-terminal globular region
      (subdomains C1-C5), and truncated alpha3(VI) N6-C1, N6-C2, N6-C3, and N6-C4
      chains, all associated with endogenous alpha1(VI) and alpha2(VI) to form collagen
      VI monomers, dimers and tetramers, which were secreted. These data demonstrate
      that subdomains C2-C5 are not required for monomer, dimer or tetramer assembly,
      and suggest that the important chain selection interactions involve the C1
      subdomains. In contrast to tetramers containing control alpha3(VI) N6-C5 chains,
      tetramers containing truncated alpha3(VI) chains were unable to associate
      efficiently end-to-end in the medium and did not form a significant extracellular
      matrix, demonstrating that the alpha3(VI) C5 domain plays a crucial role in
      collagen VI microfibril assembly. The alpha3(VI) C5 domain is present in the
      extracellular matrix of SaOS-2 N6-C5 expressing cells and fibroblasts
      demonstrating that processing of the C-terminal region of the alpha3(VI) chain is
      not essential for microfibril formation.

PMID- 16613850
TI  - Akt regulates basal and induced processing of NF-kappaB2 (p100) to p52.
AB  - NF-kappaB is a family of transcription factors important for innate and adaptive
      immunity. NF-kappaB is restricted to the cytoplasm by inhibitory proteins that
      are degraded when specifically phosphorylated, permitting NF-kappaB to enter the
      nucleus and activate target genes. Phosphorylation of the inhibitory proteins is
      mediated by an IkappaB kinase (IKK) complex, which can be composed of two
      subunits with enzymatic activity, IKKalpha and IKKbeta. The preferred substrate
      for IKKbeta is IkappaBalpha, degradation of which liberates p65 (RelA) to enter
      the nucleus where it induces genes important to innate immunity. IKKalpha
      activates a non-canonical NF-kappaB pathway in which p100 (NF-kappaB2) is
      processed to p52. Once produced, p52 can enter the nucleus and induce genes
      important to adaptive immunity. This study shows that Akt binds to and increases
      the activity of IKKalpha and thereby increases p52 production in cells.
      Constitutively active Akt augments non-canonical NF-kappaB activity, whereas
      kinase dead Akt or inhibition of phosphatidylinositol 3-kinase have the opposite
      effect. Basal and ligand-induced p52 production is reduced in mouse embryo
      fibroblasts deficient in Akt1 and Akt2 compared with parental cells. These
      observations show that Akt plays a role in activation of basal and induced non
      canonical NF-kappaB activity.

PMID- 16613851
TI  - MOZ-TIF2 alters cofactor recruitment and histone modification at the RARbeta2
      promoter: differential effects of MOZ fusion proteins on CBP- and MOZ-dependent
      activators.
AB  - MOZ-TIF2 and MOZ-CBP are leukemogenic fusion proteins associated with therapy
      induced acute myeloid leukemia. These proteins are thought to subvert normal gene
      expression in differentiating hematopoietic progenitor cells. We have previously
      shown that MOZ-TIF2 inhibits transcription by CREB-binding protein (CBP)/p300
      dependent activators such as nuclear receptors and p53. Here we have shown that
      MOZ-TIF2 associates with the RARbeta2 promoter in vivo, resulting in altered
      recruitment of CBP/p300, aberrant histone modification, and down-regulation of
      the RARbeta2 gene. In contrast, MOZ-TIF2 up-regulated transcription mediated by
      the MOZ/MYST3-dependent activator AML1/RUNX1. Both wild type MOZ and MOZ-TIF2
      were found to colocalize with AML1, and MOZ-TIF2 was recruited to an AML1 target
      promoter. A MOZ-CBP fusion protein showed similar functions to MOZ-TIF2 in that
      it inhibited retinoic acid receptor-mediated transcription but enhanced AML1
      reporter activation. Although it contains almost the entire CBP sequence, MOZ-CBP
      does not appear to associate with PML bodies. In summary, our results indicate
      that leukemogenic MOZ fusion proteins have differential effects on the activities
      of CBP-dependent and MOZ-dependent activators because of their ability to alter
      cofactor recruitment and chromatin modification at target promoters.

PMID- 16613852
TI  - Transformation by the Rho-specific guanine nucleotide exchange factor Dbs
      requires ROCK I-mediated phosphorylation of myosin light chain.
AB  - Dbs was identified in a cDNA-based expression screen for sequences that can cause
      malignant growth when expressed in murine fibroblasts. In previous studies we
      have shown that Dbs is a Rho-specific guanine nucleotide exchange factor that can
      activate RhoA and/or Cdc42 in a cell-specific manner. In this current study we
      have used a combination of genetic and pharmacological approaches to examine the
      relative contributions of RhoA x PRK and RhoA x ROCK signaling to Dbs
      transformation. Our analysis indicates that ROCK is activated in Dbs-transformed
      cells and that Dbs transformation is dependent upon ROCK I activity. In contrast,
      there appears to be no requirement for PRK activation in Dbs transformation. Dbs
      transformation is also associated with increased phosphorylation of myosin light
      chain and stress fiber formation, both of which occur in a ROCK-dependent manner.
      Suppression of myosin light chain expression by small interfering RNAs impairs
      Dbs focus formation, thus establishing a direct link between actinomyosin
      contraction and Rho-specific guanine nucleotide exchange factor transformation.

PMID- 16613853
TI  - Histone H3 lysine 4 dimethylation signals the transcriptional competence of the
      adiponectin promoter in preadipocytes.
AB  - Adipogenesis is regulated by a coordinated cascade of sequence-specific
      transcription factors and coregulators with chromatin-modifying activities that
      are between them responsible for the establishment of the gene expression pattern
      of mature adipocytes. Here we examine the histone H3 post-translational
      modifications occurring at the promoters of key adipogenic genes during adipocyte
      differentiation. We show that the promoters of apM1, glut4, gpd1, and leptin are
      enriched in dimethylated histone H3 Lys4 (H3-K4) in 3T3-L1 fibroblasts, where
      none of these genes are yet expressed. A detailed study of the apM1 locus shows
      that H3-K4 dimethylation is restricted to the promoter region in undifferentiated
      cells and associates with RNA polymerase II (pol II) loading. The beginning of
      apM1 transcription at the early stages of adipogenesis coincides with promoter H3
      hyperacetylation and H3-K4 trimethylation. At the coding region, H3 acetylation
      and dimethylation, as well as pol II binding, are found in cells at later stages
      of differentiation, when apM1 transcription reaches its maximal peak. This same
      pattern of histone modifications is detected in mouse primary preadipocytes and
      adipocytes but not in a related fibroblast cell line that is not committed to an
      adipocyte fate. Inhibition of H3-K4 methylation by treatment of 3T3-L1 cells with
      methylthioadenosine results in decreased apM1 gene expression as well as
      decreased adipogenesis. Taken together, our data indicate that H3-K4
      dimethylation and pol II binding to the promoter of key adipogenic genes are
      distinguishing marks of cells that have undergone determination to a preadipocyte
      stage.

PMID- 16613854
TI  - Amide hydrogen exchange reveals conformational changes in hsp70 chaperones
      important for allosteric regulation.
AB  - Hsp70 chaperones assist protein folding processes by a nucleotide-driven cycle of
      substrate binding and release. Although structural information is available for
      the isolated nucleotide-binding (NBD) and substrate-binding domains (SBD) in the
      high affinity conformation, the low affinity conformations and the conformational
      changes associated with mutual allosteric regulation remained largely enigmatic.
      By using amide hydrogen exchange in combination with mass spectrometry, we
      analyzed the Escherichia coli Hsp70 homologue DnaK as full-length protein and its
      individual domains in the nucleotide-free and ATP-bound conformation. We found a
      surprising degree of flexibility in both domains. The comparison of the full
      length protein with the isolated domains demonstrates a mutual stabilization of
      both domains. This protection from solvent was most pronounced and in addition
      was nucleotide-dependent in the lowerbeta-sheet of the SBD and the loop that
      connects the last beta-strand with helix alphaA. Interestingly, the linker
      region, which connects NBD and SBD and which is close to the protected loop in
      the SBD, is solvent-exposed in the absence of nucleotide and completely protected
      from hydrogen exchange in the presence of ATP. Peptide binding to DnaK.ATP
      reverts the ATP-induced conformational changes in the linker and selected parts
      of the NBD. Our data outline a pathway for allosteric interdomain control and
      suggest an important role of the linker and the base of helix alphaA.

PMID- 16613855
TI  - Opposing roles of zyxin/LPP ACTA repeats and the LIM domain region in cell-cell
      adhesion.
AB  - Cadherins mediate cell-cell adhesion by linking cell junctions to actin networks.
      Although several actin regulatory systems have been implicated in cell-cell
      adhesion, it remains unclear how such systems drive cadherin-actin network
      formation and how they are regulated to coincide with initiation of adhesion.
      Previous work implicated VASP in assembly of cell-cell junctions in keratinocytes
      and the VASP-binding protein zyxin colocalizes with VASP at cell-cell junctions.
      Here we examine how domains in zyxin and its relative LPP contribute to cell-cell
      junction assembly. Using a quantitative assay for cell-cell adhesion, we
      demonstrate that zyxin and LPP function to increase the rate of early cell-cell
      junction assembly through the VASP-binding ActA repeat region. We also identify
      the LIM region of zyxin and LPP to be a regulatory domain that blocks function of
      these proteins. Deletion of the LIM domains drives adhesion and increases VASP
      level in detergent insoluble cadherin-actin. Dominant-negative zyxin/LPP mutants
      reduce the rate of adhesion, lower VASP levels in detergent-insoluble cadherin
      actin networks, and allow for the accumulation of capping protein at cell-cell
      contacts. These data implicate the LIM domains of zyxin and LPP in regulating
      cell-cell junction assembly through VASP.

PMID- 16613856
TI  - Bone morphogenetic protein-2 stimulates Runx2 acetylation.
AB  - Runx2/Cbfa1/Pebp2aA is a global regulator of osteogenesis and is crucial for
      regulating the expression of bone-specific genes. Runx2 is a major target of the
      bone morphogenetic protein (BMP) pathway. Genetic analysis has revealed that
      Runx2 is degraded through a Smurf-mediated ubiquitination pathway, and its
      activity is inhibited by HDAC4. Here, we demonstrate the molecular link between
      Smurf, HDACs and Runx2, in BMP signaling. BMP-2 signaling stimulates p300
      mediated Runx2 acetylation, increasing transactivation activity and inhibiting
      Smurf1-mediated degradation of Runx2. HDAC4 and HDAC5 dea-cetylate Runx2,
      allowing the protein to undergo Smurf-mediated degradation. Inhibition of HDAC
      increases Runx2 acetylation, and potentiates BMP-2-stimulated osteoblast
      differentiation and increases bone formation. These results demonstrate that the
      level of Runx2 is controlled by a dynamic equilibrium of acetylation,
      deacetylation, and ubiquitination. These findings have important medical
      implications because BMPs and Runx2 are of tremendous interest with regard to the
      development of therapeutic agents against bone diseases.

PMID- 16613857
TI  - Cyclin D1-cdk4 induce runx2 ubiquitination and degradation.
AB  - Runx2 is a Runt domain transcription factor involved in the activation of genes
      encoding osteoblast and chondrocyte-specific proteins. Runx2 activity is
      regulated by transcriptional and post-transcriptional mechanisms. The functional
      significance of the post-translational modification of Runx2 has not been fully
      defined. We show that cyclin D1-Cdk4 induce Runx2 degradation in an
      ubiquitination-proteasome-dependent manner. Mutagenesis of Runx2 serine-472, a
      consensus Cdk site, to alanine increases the half-life of Runx2 and causes loss
      of sensitivity to cyclin D1-induced Runx2 degradation. The targeted Runx2
      degradation by cyclin D1 identifies a novel mechanism through which Runx2
      activity is regulated coordinately with the cell cycle machinery in bone cells.

PMID- 16613858
TI  - Erm/thyroid transcription factor 1 interactions modulate surfactant protein C
      transcription.
AB  - Expression of surfactant protein C (SP-C), which is restricted to alveolar type
      II epithelial cells of the adult lung, is critically dependent on thyroid
      transcription factor 1 (TTF-1). In the present study we have demonstrated that
      Erm, a member of the Ets family of transcription factors, is expressed in the
      distal lung epithelium during development and is also restricted to alveolar type
      II cells in the adult. Erm was up-regulated by fibroblast growth factors (FGFs)
      in culture, and blocking FGF signaling inhibited Erm expression both in vivo and
      in vitro. The SP-C minimal promoter was found to contain two potential Ets
      binding sites, and electrophoretic mobility shift assays showed that two 20-bp
      wild-type oligonucleotides containing the 5'-GGA(A/T)-3' Ets consensus binding
      motif were shifted by nuclear extracts from MLE15 cells. Co-transfection assays
      showed that Erm by itself had little effect on SP-C promoter activity but that
      Erm significantly enhanced TTF-1-mediated SP-C transcription. Mutation of one of
      the Ets binding sites reduced SP-C transcription to background levels, whereas
      mutation of the other site resulted in increased SP-C transcription. Protein
      protein interactions between Erm and TTF-1 were demonstrated by mammalian two
      hybrid assays and by co-immunoprecipitation assays. Mapping studies showed that
      the Ets domain of Erm and the combined N terminus and homeodomain of TTF-1 were
      critical for this interaction. Treatment of primary cultures of adult alveolar
      type II cells with siRNA targeting Erm diminished expression of both Erm and SP-C
      but had no effect on beta-actin or GAPDH (glyceraldehyde-3-phosphate
      dehydrogenase). Taken together, these results demonstrate that Erm is involved in
      SP-C regulation, which results from an interaction with TTF-1.

PMID- 16613859
TI  - A random-sequential mechanism for nitrite binding and active site reduction in
      copper-containing nitrite reductase.
AB  - The homotrimeric copper-containing nitrite reductase (NiR) contains one type-1
      and one type-2 copper center per monomer. Electrons enter through the type-1 site
      and are shuttled to the type-2 site where nitrite is reduced to nitric oxide. To
      investigate the catalytic mechanism of NiR the effects of pH and nitrite on the
      turnover rate in the presence of three different electron donors at saturating
      concentrations were measured. The activity of NiR was also measured
      electrochemically by exploiting direct electron transfer to the enzyme
      immobilized on a graphite rotating disk electrode. In all cases, the steady-state
      kinetics fitted excellently to a random-sequential mechanism in which electron
      transfer from the type-1 to the type-2 site is rate-limiting. At low [NO(-)(2)]
      reduction of the type-2 site precedes nitrite binding, at high [NO(-)(2)] the
      reverse occurs. Below pH 6.5, the catalytic activity diminished at higher nitrite
      concentrations, in agreement with electron transfer being slower to the nitrite
      bound type-2 site than to the water-bound type-2 site. Above pH 6.5, substrate
      activation is observed, in agreement with electron transfer to the nitrite-bound
      type-2 site being faster than electron transfer to the hydroxyl-bound type-2
      site. To study the effect of slower electron transfer between the type-1 and type
      2 site, NiR M150T was used. It has a type-1 site with a 125-mV higher midpoint
      potential and a 0.3-eV higher reorganization energy leading to an approximately
      50-fold slower intramolecular electron transfer to the type-2 site. The results
      confirm that NiR employs a random-sequential mechanism.

PMID- 16613860
TI  - The structure of G protein-coupled receptor kinase (GRK)-6 defines a second
      lineage of GRKs.
AB  - We describe the 2.6-A crystal structure of human G protein-coupled receptor
      kinase (GRK)-6, a key regulator of dopaminergic signaling and lymphocyte
      chemotaxis. GRK6 is a member of the GRK4 subfamily of GRKs, which is represented
      in most, if not all, metazoans. Comparison of GRK6 with GRK2 confirms that the
      catalytic core of all GRKs consists of intimately associated kinase and regulator
      of G protein signaling (RGS) homology domains. Despite being in complex with an
      ATP analog, the kinase domain of GRK6 remains in an open, presumably inactive
      conformation, suggesting that G protein-coupled receptors activate GRKs by
      inducing kinase domain closure. The structure reveals a putative phospholipid
      binding site near the N terminus of GRK6 and structural elements within the
      kinase substrate channel that likely influence G protein-coupled receptor access
      and specificity. The crystalline GRK6 RGS homology domain forms an extensive
      dimer interface using conserved hydrophobic residues distinct from those in GRK2
      that bind Galpha(q), although dimerization does not appear to occur in solution
      and is not required for receptor phosphorylation.

PMID- 16613861
TI  - A phosphoinositide 3-kinase-AKT-nitric oxide-cGMP signaling pathway in
      stimulating platelet secretion and aggregation.
AB  - Phosphoinositide 3-kinase (PI3K) and Akt play important roles in platelet
      activation. However, the downstream mechanisms mediating their functions are
      unclear. We have recently shown that nitric-oxide (NO) synthase 3 and cGMP
      dependent protein kinase stimulate platelet secretion and aggregation. Here we
      show that PI3K-mediated Akt activation plays an important role in agonist
      stimulated platelet NO synthesis and cGMP elevation. Agonist-induced elevation of
      NO and cGMP was inhibited by Akt inhibitors and reduced in Akt-1 knock-out
      platelets. Akt-1 knock-out or Akt inhibitor-treated platelets showed reduced
      platelet secretion and aggregation in response to low concentrations of agonists,
      which can be reversed by low concentrations of 8-bromo-cGMP or sodium
      nitroprusside (an NO donor). Similarly, PI3K inhibitors diminished elevation of
      cGMP and inhibited platelet secretion and the second wave platelet aggregation,
      which was also partially reversed by 8-bromo-cGMP. These results indicate that
      the NO-cGMP pathway is an important downstream mechanism mediating PI3K and Akt
      signals leading to platelet secretion and aggregation. Conversely, the PI3K-Akt
      pathway is the major upstream mechanism responsible for activating the NO-cGMP
      pathway in platelets. Thus, this study delineates a novel platelet activation
      pathway involving sequential activation of PI3K, Akt, nitric-oxide synthase 3,
      sGC, and cGMP-dependent protein kinase.

PMID- 16613862
TI  - Common phylogenetic origin of protamine-like (PL) proteins and histone H1:
      Evidence from bivalve PL genes.
AB  - Sperm nuclear basic proteins (SNBPs) can be grouped into three main categories:
      histone (H) type, protamine (P) type, and protamine-like (PL) type. Protamine
      like SNBPs represent the most structurally heterogeneous group, consisting of
      basic proteins which are rich in both lysine and arginine amino acids. The PL
      proteins replace most of the histones during spermiogenesis but to a lesser
      extent than the proteins of the P type. In most instances, PLs coexist in the
      mature sperm with a full histone complement. The replacement of histones by
      protamines in the mature sperm is a characteristic feature presented by those
      taxa located at the uppermost evolutionary branches of protostome and
      deuterostome evolution, while the histone type of SNBPs is predominantly found in
      the sperm of taxa which arose early in metazoan evolution; giving rise to the
      hypothesis that protamines may have evolved through a PL type intermediate from a
      primitive histone ancestor. The structural similarities observed between PL and
      H1 proteins, which were first described in bivalve molluscs, provide a unique
      insight into the evolutionary mechanisms underlying SNBP evolution. Although the
      evolution of SNBPs has been exhaustively analyzed in the last 10 years, the
      origin of PLs in relation to the evolution of the histone H1 family still remains
      obscure. In this work, we present the first complete gene sequence for two of
      these genes (PL-III and PL-II/PL-IV) in the mussel Mytilus and analyze the
      protein evolution of histone H1 and SNBPs, and we provide evidence that indicates
      that H1 histones and PLs are the direct descendants of an ancient group of
      "orphon" H1 replication-dependent histones which were excluded to solitary
      genomic regions as early in metazoan evolution as before the differentiation of
      bilaterians. While the replication-independent H1 lineage evolved following a
      birth-and-death process, the SNBP lineage has been subject to a purifying process
      that shifted toward adaptive selection at the time of the differentiation of
      arginine-rich Ps.

PMID- 16613863
TI  - How should the effectiveness of Social Stories to modify the behaviour of
      children on the autistic spectrum be tested? Lessons from the literature.
AB  - Social Stories are an extensively used intervention to address behaviour
      difficulties of children on the autistic spectrum. This article summarizes what
      Social Stories are and sets out to determine whether there is any relevant
      literature demonstrating the effectiveness of this intervention. Whilst the
      existing literature suggests positive findings with respect to the effectiveness
      of Social Stories, there is considerable variability in the quality of research
      methodology, with no single study employing comprehensive, stringent standards.
      This article highlights the factors that should be considered and addressed when
      testing the effectiveness of Social Stories, as a means of informing future
      research.

PMID- 16613864
TI  - Social comparison processes and depressive symptoms in children and adolescents
      with Asperger syndrome.
AB  - The present study investigated the relationship between social comparison
      processes and depressive symptoms in 36 participants (34 males and two females)
      aged 10 to 16 years with Asperger syndrome. Participants completed the Social
      Comparison Scale and the Children's Depression Inventory. Depressive symptoms
      were significantly correlated with the SCS (r = 0.52, p = 0.001), specifically
      perceived group membership (r = 0.56, p < 0.001). A regression analysis revealed
      that perceived group membership significantly and independently predicted
      depression scores (beta= 0.56, p = 0.002). It is suggested social comparison is a
      salient factor related to depressive symptoms in this group, and interventions
      involving adolescents with AS should therefore address this factor.

PMID- 16613865
TI  - Sensory and attention abnormalities in autistic spectrum disorders.
AB  - Individuals with autistic spectrum disorders (ASDs) often experience, describe
      and exhibit unusual patterns of sensation and attention. These anomalies have
      been hypothesized to result from overarousal and consequent overfocused
      attention. Parents of individuals with ASD rated items in three domains, 'sensory
      overreactivity', 'sensory underreactivity' and 'sensory seeking behaviors', of an
      expanded version of the Sensory Profile, a 103-item rating scale developed for
      the present study. Parents also rated symptom severity, overselective attention
      and exceptional memory, and completed the Vineland Adaptive Behavior Scales. Of
      222 rated subjects, 144 had complete data. Cluster analysis showed the predicted
      overfocused pattern of sensation and attention, comprising overreactivity,
      perseverative behavior and interests, overfocused attention and exceptional
      memory in 43 percent of this sample. This pattern was striking in 10 percent. The
      neurological basis of overreactivity and overfocusing is discussed in relation to
      the overarousal hypothesis. Attention is drawn to its considerable prevalence in
      the ASD population.

PMID- 16613866
TI  - Theory of mind abilities in young siblings of children with autism.
AB  - Deficits in theory of mind (ToM), evident in most individuals with autism, have
      been suggested as a core deficit of autism. ToM difficulties in young siblings of
      children with autism (SIBS-A) compared to siblings of typically developing
      children (SIBS-TD) would place the former within the broad phenotype. We examined
      ToM's possible associations with measures of language, cognition, and daily
      living skills. Participants comprised 24 SIBS-A and 24 matched SIBSTD aged 4.6
      years. They completed the false belief and the strange stories tasks. We also
      collected measures of verbal and cognitive ability and daily living skills. Non
      significant differences emerged between the groups on both ToM tasks. Differences
      did emerge in within-group associations between ToM ability and receptive
      language. The conclusion is that SIBS-A show resilience in ToM abilities.
      Possibly, these deficits are not genetically transferred to siblings, at least as
      measured in laboratory-based ToM tasks.

PMID- 16613867
TI  - IgA antibodies in Rett syndrome.
AB  - The level of IgA antibodies to gluten and gliadin proteins found in grains and to
      casein found in milk, as well as the level of IgG to gluten and gliadin, have
      been examined in 23 girls with Rett syndrome and 53 controls. Highly
      statistically significant increases were found for the Rett population compared
      to the controls. The reason for this remains unknown, but because IgA antibodies
      reflect the uptake of proteins and/or epitopes of proteins from the gut, this may
      be indicative of increased protein uptake.

PMID- 16613868
TI  - A comparative study of the spontaneous social interactions of children with high
      functioning autism and children with Asperger's disorder.
AB  - A comparative observational study was undertaken of the spontaneous social
      interactions of children with high-functioning autism and Asperger's disorder.
      The sample comprised 20 children with high-functioning autism, 19 children with
      Asperger's disorder and 17 typically developing children matched on chronological
      age and overall mental age. A one-zero time sampling technique was used in live
      coding of the children's spontaneous social and play behaviours in the
      schoolyard. Few differences were found between children with high-functioning
      autism and Asperger's disorder on the dimensions of social interaction
      investigated. In contrast, the social behaviour of both clinical samples often
      deviated markedly from that of the typically developing children. The findings
      confirmed that although children with high-functioning autism or Asperger's
      disorder are often socially isolated relative to their typically developing
      peers, they are capable of spontaneously engaging socially with other children.
      The results were supportive of the hypothesis that Asperger's disorder is on a
      continuum with autistic disorder.

PMID- 16613869
TI  - Ammonia (NH3), nitric oxide (NO) and nitrous oxide (N2O)--the connection with
      infantile autism.

PMID- 16613870
TI  - Extrusion of Ca2+ from mouse motor terminal mitochondria via a Na+-Ca2+ exchanger
      increases post-tetanic evoked release.
AB  - Mitochondria sequester much of the Ca2+ that enters motor nerve terminals during
      repetitive stimulation at frequencies exceeding 10-20 Hz. We studied the post
      stimulation extrusion of Ca2+ from mitochondria by measuring changes in matrix
      [Ca2+] with fluorescent indicators loaded into motor terminal mitochondria in the
      mouse levator auris longus muscle. Trains of action potentials at 50 Hz produced
      a rapid increase in mitochondrial [Ca2+] followed by a plateau, which was usually
      maintained after the end of the stimulus train and then slowly decayed back to
      baseline. Increasing the Ca2+ load delivered to the terminal by increasing the
      number of stimuli (from 500 to 2000) or the stimulation frequency (from 50 to 100
      Hz), by increasing bath [Ca2+], or by prolonging the action potential with 3,4
      diaminopyridine (100 microM) prolonged the post-stimulation decay of
      mitochondrial [Ca2+] without increasing the amplitude of the plateau during
      stimulation. Inhibiting the opening of the mitochondrial permeability transition
      pore with cyclosporin A (5 microM) had no significant effect on the decay of
      mitochondrial [Ca2+]. Inhibition of the mitochondrial Na+-Ca2+ exchanger with CGP
      37157 (50 microM) dramatically prolonged the post-stimulation decay of
      mitochondrial [Ca2+], reduced post-stimulation residual cytosolic [Ca2+], and
      reduced the amplitude of endplate potentials evoked after the end of a stimulus
      train in the presence of both low and normal bath [Ca2+]. These findings suggest
      that Ca2+ extrusion from motor terminal mitochondria occurs primarily via the
      mitochondrial Na+-Ca2+ exchanger and helps to sustain post-tetanic transmitter
      release at mouse neuromuscular junctions.

PMID- 16613871
TI  - Subthalamic stimulation evokes complex EPSCs in the rat substantia nigra pars
      reticulata in vitro.
AB  - The subthalamic nucleus (STN) plays an important role in movement control by
      exerting its excitatory influence on the substantia nigra pars reticulata (SNR),
      a major output structure of the basal ganglia. Moreover, excessive burst firing
      of SNR neurons seen in Parkinson's disease has been attributed to excessive
      transmission in the subthalamonigral pathway. Using the 'blind' whole-cell patch
      clamp recording technique in rat brain slices, we found that focal electrical
      stimulation of the STN evoked complex, long-duration excitatory postsynaptic
      currents (EPSCs) in SNR neurons. Complex EPSCs lasted 200-500 ms and consisted of
      an initial monosynaptic EPSC followed by a series of late EPSCs superimposed on a
      slow inward shift in holding current. Focal stimulation of regions outside the
      STN failed to evoke complex EPSCs. The late component of complex EPSCs was
      markedly reduced by ionotropic glutamate receptor antagonists (2-amino-5
      phosphonopentanoic acid and 6-cyano-7-nitro-quinoxalone) and by a GABAA receptor
      agonist (isoguvacine) when these agents were applied directly to the STN using a
      fast-flow microapplicator. Moreover, the complex EPSC was greatly enhanced by
      bath application of the GABAA receptor antagonists picrotoxin or bicuculline.
      These data suggest that recurrent glutamate synapses in the STN generate
      polysynaptic, complex EPSCs that are under tonic inhibition by GABA. Because
      complex EPSCs are expected to generate bursts of action potentials in SNR
      neurons, we suggest that complex EPSCs may contribute to the pathological burst
      firing that is associated with the symptoms of Parkinson's disease.

PMID- 16613872
TI  - Activity-dependent synaptic plasticity in the supraoptic nucleus of the rat
      hypothalamus.
AB  - Activity-dependent long-term synaptic changes were investigated at glutamatergic
      synapses in the supraoptic nucleus (SON) of the rat hypothalamus. In acute
      hypothalamic slices, high frequency stimulation (HFS) of afferent fibres caused
      long-term potentiation (LTP) of the amplitude of AMPA receptor-mediated
      excitatory postsynaptic currents (EPSCs) recorded with the whole-cell patch-clamp
      technique. LTP was also obtained in response to membrane depolarization paired
      with mild afferent stimulation. On the other hand, stimulating the inputs at 5 Hz
      for 3 min at resting membrane potential caused long-term depression (LTD) of
      excitatory transmission in the SON. These forms of synaptic plasticity required
      the activation of NMDA receptors since they were abolished in the presence of D
      AP5 or ifenprodil, two selective blockers of these receptors. Analysis of paired
      pulse facilitation and trial-to-trial variability indicated that LTP and LTD were
      not associated with changes in the probability of transmitter release, thereby
      suggesting that the locus of expression of these phenomena was postsynaptic.
      Using sharp microelectrode recordings in a hypothalamic explant preparation, we
      found that HFS also generates LTP at functionally defined glutamatergic synapses
      formed between the organum vasculosum lamina terminalis and SON neurons. Taken
      together, our findings indicate that glutamatergic synapses in the SON exhibit
      activity-dependent long-term synaptic changes similar to those prevailing in
      other brain areas. Such forms of plasticity could play an important role in the
      context of physiological responses, like dehydration or lactation, where the
      activity of presynaptic glutamatergic neurons is strongly increased.

PMID- 16613873
TI  - Direct excitation of deep dorsal horn neurones in the rat spinal cord by the
      activation of postsynaptic P2X receptors.
AB  - ATP mediates somatosensory transmission in the spinal cord through the activation
      of P2X receptors. Nonetheless, the functional significance of postsynaptic P2X
      receptors in spinal deep dorsal horn neurones is still not yet well understood.
      Using the whole-cell patch-clamp technique, we investigated whether the
      activation of postsynaptic P2X receptors can modulate the synaptic transmission
      in lamina V neurones of postnatal day (P) 9-12 spinal cord slices. At a holding
      potential of -70 mV, ATPgammaS (100 microm), a nonhydrolysable ATP analogue,
      generated an inward current, which was resistant to tetrodotoxin (1 microm) in
      61% of the lamina V neurones. The ATPgammaS-induced inward current was
      accompanied by a significant increase in the frequency of glutamatergic miniature
      excitatory postsynaptic currents (mEPSCs) in the majority of lamina V neurones.
      The ATPgammaS-induced inward current was not reproduced by P2Y receptor agonists,
      UTP (100 microm), UDP (100 microm), and 2-methylthio ADP (100 microm), and it was
      also not affected by the addition of guanosine-5'-O-(2-thiodiphosphate)
      (GDPbetaS) into the pipette solution, thus suggesting that ionotropic P2X
      receptors were activated by ATPgammaS instead of metabotropic P2Y receptors. On
      the other hand, alpha,beta-methylene ATP (100 microm) did not change any membrane
      current, but instead increased the mEPSC frequency in the majority of lamina V
      neurones. The ATPgammaS-induced inward current was suppressed by
      pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (10 microm), but
      not by trinitrophenyl-ATP (TNP-ATP) (1 microm). Furthermore, we found that
      ATPgammaS (100 microm) produced a clear inward current which was observed in all
      lamina V neurones over P16 spinal cord slices, in contrast to P9-12. These
      results indicate that distinct subtypes of P2X receptors were functionally
      expressed at the post- and presynaptic sites in lamina V neurones, both of which
      may contribute to the hyperexcitability of lamina V in a different manner. In
      addition, the data relating to the developmental increase in the functional P2X
      receptors suggest that purinergic signalling may thus be more common in
      somatosensory transmission with maturation.

PMID- 16613874
TI  - Electrophysiological diversity of the dorsal raphe cells across the sleep-wake
      cycle of the rat.
AB  - Through their widespread projections to the entire brain, dorsal raphe cells
      participate in many physiological functions and are associated with
      neuropsychiatric disorders. In previous studies, the width of action potentials
      was used as a criterion to identify putative serotonergic neurons, and to
      demonstrate that cells with broad spikes were more active in wakefulness, slowed
      down their activity in slow wave sleep and became virtually silent during
      paradoxical sleep. However, recent studies reported that about half of these
      presumed serotonergic cells were not immunoreactive for tyrosine hydroxylase.
      Here, we re-examine the electrophysiological properties of dorsal raphe cells
      across the sleep-wake cycle in rats by the extracellular recording of a large
      sample of single units (n = 770). We identified two major types of cells, which
      differ in spike waveform: a first population characterized by broad, mostly
      positive spikes, and a second one displaying symmetrical positive-negative spikes
      with a large distribution of spike durations (0.6-3.2 ms). Although we found
      classical broad-spike cells that were more active in wakefulness, we also found
      that about one-third of these cells increased or did not change their firing rate
      during sleep compared with wakefulness. Moreover, 62% of the latter cells were
      active in paradoxical sleep when most of raphe cells were silent. Such a
      diversity in the neuronal firing behaviour is important in the light of the
      recent controversy regarding the neurochemical identity of dorsal raphe cells
      exhibiting broad spikes. Our results also suggest that the dorsal raphe contains
      subpopulations of neurons with reciprocal activity across the sleep-wake cycle.

PMID- 16613875
TI  - Integrative spike dynamics of rat CA1 neurons: a multineuronal imaging study.
AB  - The brain operates through a coordinated interplay of numerous neurons, yet
      little is known about the collective behaviour of individual neurons embedded in
      a huge network. We used large-scale optical recordings to address synaptic
      integration in hundreds of neurons. In hippocampal slice cultures bolus-loaded
      with Ca2+ fluorophores, we stimulated the Schaffer collaterals and monitored the
      aggregate presynaptic activity from the stratum radiatum and individual
      postsynaptic spikes from the CA1 stratum pyramidale. Single neurons responded to
      varying synaptic inputs with unreliable spikes, but at the population level, the
      networks stably output a linear sum of synaptic inputs. Nonetheless, the network
      activity, even though given constant stimuli, varied from trial to trial. This
      variation emerged through time-varying recruitment of different neuron subsets,
      which were shaped by correlated background noise. We also mapped the input
      frequency preference in spiking activity and found that the majority of CA1
      neurons fired in response to a limited range of presynaptic firing rates (20-40
      Hz), acting like a band-pass filter, although a few neurons had high pass-like or
      low pass-like characteristics. This frequency selectivity depended on phasic
      inhibitory transmission. Thus, our imaging approach enables the linking of single
      cell behaviours to their communal dynamics, and we discovered that, even in a
      relatively simple CA1 circuit, neurons could be engaged in concordant information
      processing.

PMID- 16613876
TI  - AMPK and cell proliferation--AMPK as a therapeutic target for atherosclerosis and
      cancer.
AB  - AMPK is a serine/threonine protein kinase, which serves as an energy sensor in
      all eukaryotic cell types. Published studies indicate that AMPK activation
      strongly suppresses cell proliferation in non-malignant cells as well as in
      tumour cells. These actions of AMPK appear to be mediated through multiple
      mechanisms including regulation of the cell cycle and inhibition of protein
      synthesis, de novo fatty acid synthesis, specifically the generation of
      mevalonate as well as other products downstream of mevalonate in the cholesterol
      synthesis pathway. Cell cycle regulation by AMPK is mediated by up-regulation of
      the p53-p21 axis as well as regulation of TSC2-mTOR (mammalian target of
      rapamycin) pathway. The AMPK signalling network contains a number of tumour
      suppressor genes including LKB1, p53, TSC1 and TSC2, and overcomes growth factor
      signalling from a variety of stimuli (via growth factors and by abnormal
      regulation of cellular proto-oncogenes including PI3K, Akt and ERK). These
      observations suggest that AMPK activation is a logical therapeutic target for
      diseases rooted in cellular proliferation, including atherosclerosis and cancer.
      In this review, we discuss about exciting recent advances indicating that AMPK
      functions as a suppressor of cell proliferation by controlling a variety of
      cellular events in normal cells as well as in tumour cells.

PMID- 16613877
TI  - The influence of intracellular lactate and H+ on cell volume in amphibian
      skeletal muscle.
AB  - The combined effects of intracellular lactate and proton accumulation on cell
      volume, Vc, were investigated in resting Rana temporaria striated muscle fibres.
      Intracellular lactate and H+ concentrations were simultaneously increased by
      exposing resting muscle fibres to extracellular solutions that contained 20-80 mm
      sodium lactate. Cellular H+ and lactate entry was confirmed using pH-sensitive
      electrodes and 1H-NMR, respectively, and effects on Vc were measured using
      confocal microscope xz-scanning. Exposure to extracellular lactate up to 80 mm
      produced significant changes in pH and intracellular lactate (from a pH of 7.24
      +/- 0.03, n = 8, and 4.65 +/- 1.07 mm, n = 6, respectively, in control fibres, to
      6.59 +/- 0.03, n = 4, and 26.41 +/- 0.92 mm, n = 3, respectively) that were
      comparable to those observed following fatiguing stimulation (6.30-6.70 and 18.04
      +/- 1.78 mm, n = 6, respectively). Yet, the increase in intracellular osmolarity
      expected from such an increase in intracellular lactate did not significantly
      alter Vc. Simulation of these experimental results, modified from the charge
      difference model of Fraser & Huang, demonstrated that such experimental
      manoeuvres produced changes in intracellular [H+] and [lactate] comparable to
      those observed during muscle fatigue, and accounted for this paradoxical
      conservation of Vc through balancing negative osmotic effects resulting from the
      net cation efflux that would follow a titration of intracellular membrane
      impermeant anions by the intracellular accumulation of protons. It demonstrated
      that with established physiological values for intracellular buffering capacity
      and the permeability ratio of lactic acid and anionic lactate, P(LacH): P(Lac-),
      this would provide a mechanism that precisely balanced any effect on cell volume
      resulting from lactate accumulation during exercise.

PMID- 16613878
TI  - Changes in the histaminergic system during vestibular compensation in the cat.
AB  - To determine how the histaminergic system is implicated in vestibular
      compensation, we studied the changes in histidine decarboxylase (HDC; the enzyme
      synthesizing histamine) mRNA regulation in the tuberomammillary (TM) nuclei of
      cats killed 1 week, 3 weeks and 3 months after unilateral vestibular neurectomy
      (UVN). We also used one- and two-step bilateral vestibular neurectomized (BVN)
      cats to determine whether HDC mRNA regulation depended on the asymmetrical
      vestibular input received by the TM nuclei neurons. In addition, we analysed the
      HDC mRNA changes in the TM nuclei and the recovery of behavioural functions in
      UVN cats treated with thioperamide, a pure histaminergic drug. Finally, we
      quantified binding to histamine H3 receptors (H3Rs) in the medial vestibular
      nucleus (VN) by means of a histamine H3R agonist ([3H]N-alpha-methylhistamine) in
      order to further investigate the sites and mechanisms of action of histamine in
      this structure. This study shows that UVN increases HDC mRNA expression in the
      ipsilateral TM nucleus at 1 week. This increased expression persisted 3 weeks
      after UVN, and regained control values at 3 months. HDC mRNA expression was
      unchanged in the one-step BVN cats but showed mirror asymmetrical increases in
      the two-step BVN compared to the 1 week UVN cats. Three weeks' thioperamide
      treatment induced a bilateral HDC mRNA up-regulation in the UVN cats, which was
      higher than in the untreated UVN group. Binding to histamine H3Rs in the MVN
      showed a strong bilateral decrease after thioperamide treatment, while it was
      reduced ipsilaterally in the UVN cats. That such changes of the histaminergic
      system induced by vestibular lesion and treatment may play a functional role in
      vestibular compensation is strongly supported by the behavioural data. Indeed,
      spontaneous nystagmus, posture and locomotor balance were rapidly recovered in
      the UVN cats treated with thioperamide. These results demonstrate that changes in
      histamine levels are related to vestibular compensation.

PMID- 16613879
TI  - cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in
      human pancreatic beta cells and rat INS-1 cells.
AB  - The Epac family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs,
      also known as Epac1 and Epac2) mediate stimulatory actions of the second
      messenger cAMP on insulin secretion from pancreatic beta cells. Because Epac2 is
      reported to interact in vitro with the isolated nucleotide-binding fold-1 (NBF-1)
      of the beta-cell sulphonylurea receptor-1 (SUR1), we hypothesized that cAMP might
      act via Epac1 and/or Epac2 to inhibit beta-cell ATP-sensitive K+ channels (K(ATP)
      channels; a hetero-octomer of SUR1 and Kir6.2). If so, Epac-mediated inhibition
      of K(ATP) channels might explain prior reports that cAMP-elevating agents promote
      beta-cell depolarization, Ca2+ influx and insulin secretion. Here we report that
      Epac-selective cAMP analogues (2'-O-Me-cAMP; 8-pCPT-2'-O-Me-cAMP; 8-pMeOPT-2'-O
      Me-cAMP), but not a cGMP analogue (2'-O-Me-cGMP), inhibit the function of K(ATP)
      channels in human beta cells and rat INS-1 insulin-secreting cells. Inhibition of
      K(ATP) channels is also observed when cAMP, itself, is administered
      intracellularly, whereas no such effect is observed upon administration N6-Bnz
      cAMP, a cAMP analogue that activates protein kinase A (PKA) but not Epac. The
      inhibitory actions of Epac-selective cAMP analogues at K(ATP) channels are
      mimicked by a cAMP agonist (8-Bromoadenosine-3', 5'-cyclic monophosphorothioate,
      Sp-isomer, Sp-8-Br-cAMPS), but not a cAMP antagonist (8-Bromoadenosine-3', 5'
      cyclic monophosphorothioate, Rp-isomer, Rp-8-Br-cAMPS), and are abrogated
      following transfection of INS-1 cells with a dominant-negative Epac1 that fails
      to bind cAMP. Because both Epac1 and Epac2 coimmunoprecipitate with full-length
      SUR1 in HEK cell lysates, such findings delineate a novel mechanism of second
      messenger signal transduction in which cAMP acts via Epac to modulate ion channel
      function, an effect measurable as the inhibition of K(ATP) channel activity in
      pancreatic beta cells.

PMID- 16613880
TI  - Frequency-current relationships of rat hindlimb alpha-motoneurones.
AB  - The purpose of this study was to describe the frequency-current (f-I)
      relationships of hindlimb alpha-motoneurones (MNs) in both anaesthetized and
      decerebrate rats in situ. Sprague-Dawley rats (250-350 g) were anaesthetized with
      ketamine and xylazine (KX) or subjected to a precollicular decerebration prior to
      recording electrophysiological properties from sciatic nerve MNs. Motoneurones
      from KX-anaesthetized rats had a significantly (P < 0.01) hyperpolarized resting
      membrane potential and voltage threshold (Vth), increased rheobase current, and a
      trend (P = 0.06) for a smaller after-hyperpolarization (AHP) amplitude compared
      to MNs from decerebrate rats. In response to 5 s ramp current injections, MNs
      could be categorized into four f-I relationship types: (1) linear; (2) adapting;
      (3) linear + sustained; and (4) late acceleration. Types 3 and 4 demonstrated
      self-sustained firing owing to activation of persistent inward current (PIC). We
      estimated the PIC amplitude by subtracting the current at spike derecruitment
      from the current at spike recruitment. Neither estimated PIC nor f-I slopes
      differed between fast and slow MNs (slow MNs exhibited AHP half-decay times > 20
      ms) or between MNs from KX-anaesthetized and decerebrate rats. Motoneurones from
      KX-anaesthetized rats had significantly (P < 0.02) hyperpolarized ramp Vth values
      and smaller and shorter AHP amplitudes and decay times compared to MNs from
      decerebrate rats. Pentobarbitone decreased the estimated PIC amplitude and almost
      converted the f-I relationship from type 3 to type 1. In summary, MNs of animals
      subjected to KX anaesthesia required more current for spike initiation and
      rhythmic discharge but retained large PICs and self-sustained firing. The KX
      anaesthestized preparation enables direct recording of PICs in MNs from intact
      animals.

PMID- 16613881
TI  - Activation of the mTOR signalling pathway is required for pancreatic growth in
      protease-inhibitor-fed mice.
AB  - Cholecystokinin (CCK)-induced pancreatic growth in mice involves parallel
      increases in DNA and protein. The mammalian target of rapamycin (mTOR) signalling
      pathway regulates mRNA translation and its activation is implicated in growth of
      various tissues. The aim of this study was to elucidate whether mTOR activation
      is required for pancreatic growth in a mouse model of increased endogenous CCK
      release. In mice fed chow containing the synthetic protease inhibitor camostat,
      protein synthetic rates and phosphorylation of two downstream targets of mTOR,
      eukaryotic initiation factor 4E binding protein 1 (4E-BP1) and the ribosomal
      protein S6 (S6), increased in comparison with fasted controls. The camostat
      induced increases in protein synthesis and 4E-BP1 and S6 phosphorylation were
      almost totally abolished by administration of the mTOR inhibitor rapamycin 1 h
      prior to camostat feeding. In contrast, the phosphorylation of ERK1/2 and JNK and
      the expression of the early response genes c-jun, c-fos, ATF3 and egr-1 induced
      by camostat feeding were not affected by rapamycin. In mice fed camostat for 7
      days, the ratio of pancreatic to body weight increased by 143%, but when
      rapamycin was administered daily this was reduced to a 22% increase. Changes in
      pancreatic mass were paralleled by protein and DNA content following camostat
      feeding and rapamycin administration. Moreover, while BrdU incorporation, an
      indicator of DNA synthesis, was increased to 448% of control values after 2 days
      of camostat feeding, rapamycin administration completely inhibited this increase.
      We conclude that the mTOR signalling pathway is required for CCK-induced cell
      division and pancreatic growth.

PMID- 16613882
TI  - A noisy transform predicts saccadic and manual reaction times to changes in
      contrast.
AB  - One of the most important factors affecting the time taken to respond to a visual
      stimulus is contrast, and studies of reaction time can provide precise,
      quantitative information about the underlying signal processing. In this study we
      measured both saccadic and manual reaction times to step increments in target
      contrast. Our results over a range of initial contrasts are consistent with a
      simple model consisting of a noisy logarithmic transducer followed by a rise-to
      threshold accumulator. A systematic comparison with previous contrast-processing
      models also shows that the commonly used method of linear regression may not be a
      particularly sensitive tool in deciding between them. We found similar parameters
      for the contrast processor in both saccadic and manual reaction times, as might
      be expected if a common target detection stage precedes each type of reaction.

PMID- 16613883
TI  - Contributions of principal neocortical neurons to magnetoencephalography and
      electroencephalography signals.
AB  - A realistically shaped three-dimensional single-neuron model was constructed for
      each of four principal cell types in the neocortex in order to infer their
      contributions to magnetoencephalography (MEG) and electroencephalography (EEG)
      signals. For each cell, the soma was stimulated and the resulting intracellular
      current was used to compute the current dipole Q for the whole cell or separately
      for the apical and basal dendrites. The magnitude of Q is proportional to the
      magnetic field and electrical potential far from the neuron. A train of spikes
      and depolarization shift in an intracellular burst discharge were seen as spikes
      and an envelope in Q for the layer V and layer II/III pyramidal cells. The
      stellate cells lacked the envelope. As expected, the pyramidal cells produced a
      stronger Q than the stellate cells. The spikes produced by the layer V pyramidal
      cells (n = 4) varied between -0.78 and 2.97 pA m with the majority of the cells
      showing a current toward the pia (defined as positive). The basal dendrites,
      however, produced considerable spike currents. The magnitude and direction of
      dipole moment are in agreement with the distribution of the dendrites. The spikes
      in Q for the layer V pyramidal cells were produced by the transient sodium
      conductance and potassium conductance of delayed rectifier type; the conductances
      distributed along the dendrites were capable of generating spike propagation,
      which was seen in Q as the tail of a triphasic wave lasting several milliseconds.
      The envelope was similar in magnitude (-0.41 to -0.90 pA m) across the four layer
      V pyramidal cells. The spike and envelope for the layer II/III pyramidal cell
      were 0.47 and -0.29 pA m, respectively; these values agreed well with empirical
      and theoretical estimates for guinea pig CA3 pyramidal cells. Spikes were
      stronger for the layer IV spiny stellate (0.27 pA m) than the layer III aspiny
      stellate cell (0.06 pA m) along their best orientations. The spikes may thus be
      stronger than has been previously thought. The Q for a population of stellate
      cells may be weaker than a linear sum of their individual Q values due to their
      variable dendritic geometry. The burst discharge by pyramidal cells may be
      detectable with MEG and EEG when 10 000-50 000 cells are synchronously active.

PMID- 16613884
TI  - Rapidly cooled human sperm: no evidence of intracellular ice formation.
AB  - BACKGROUND: The cellular damage that human spermatozoa encounter at rapid rates
      of cooling has often been attributed to the formation of intracellular ice.
      However, no direct evidence of intracellular ice has been presented.
      Alternatively, the cell damage may be the result of an osmotic imbalance
      encountered during thawing. This article examines whether intracellular ice forms
      during rapid cooling or if an alternative mechanism is present. METHODS: In this
      study, human spermatozoa were cooled at a range of cooling rates from 0.3 to 3000
      degrees C/min. The ultrastructure of the samples was examined by cryo scanning
      electron microscopy and freeze substitution to determine whether intracellular
      ice formed during rapid cooling and to examine alternative mechanisms of cell
      injury during rapid cooling. RESULTS: No intracellular ice formation was detected
      at any cooling rate. Freeze substitution of cells that had been cooled at 3000
      degrees C/min and then slowly warmed showed that the cells had become plasmolysed
      and had evidence of membrane damage. CONCLUSIONS: Cell damage to human
      spermatozoa, at cooling rates of up to 3000 degrees C/min, is not caused by
      intracellular ice formation. Spermatozoa that have been cooled at high rates are
      subjected to an osmotic shock when they are thawed.

PMID- 16613885
TI  - Luteinized unruptured follicle syndrome: incidence and recurrence rate in
      infertile women with unexplained infertility undergoing intrauterine
      insemination.
AB  - BACKGROUND: The objective of this study was to determine the incidence and
      recurrence rate of luteinized unruptured follicle (LUF) syndrome in women with
      unexplained infertility undergoing intrauterine insemination (IUI). METHODS: A
      total of 167 women with unexplained infertility who underwent 292 cycles of IUI
      were enrolled in the study. All patients were treated with clomiphene citrate, 50
      150 mg/daily from day 5 to 9 of their menstrual cycle. Ultrasound examination to
      confirm ovulation was performed on the day of IUI (day 0) and every day
      thereafter for another 3 days (days 1, 2 and 3). A total of 69 women who failed
      to conceive in the first cycle and 56 women who failed to conceive in the second
      cycle underwent second and third cycles, respectively. RESULTS: Of the total 167
      patients who underwent first cycle, 42 (25%) had LUF. The incidence of LUF was
      56.5% in 69 patients who underwent a second cycle of IUI treatment, of whom 33
      patients had LUF in the first cycle with recurrence rate of 78.6%. In 56 patients
      who underwent 3 consecutive cycles, the incidence of LUF was 58.9% and recurrence
      rate of 90%. No pregnancies were recorded in patients with LUF during the study
      period. CONCLUSION: The incidence and recurrence rate of LUF are significantly
      increased in subsequent cycles of IUI. In these patients, other options of
      infertility treatment might be justified.

PMID- 16613886
TI  - Single versus double embryo transfer: cost-effectiveness analysis alongside a
      randomized clinical trial.
AB  - BACKGROUND: Twin pregnancies after IVF are still frequent and are considered high
      risk pregnancies leading to high costs. Transferring one embryo can reduce the
      twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective
      single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET)
      in an unselected patient population. METHODS: Patients starting their first IVF
      cycle were randomized between eSET and DET. Societal costs per couple were
      determined empirically, from hormonal stimulation up to 42 weeks after embryo
      transfer. An incremental cost-effectiveness ratio (ICER) was calculated,
      representing additional costs per successful pregnancy. RESULTS: Successful
      pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple
      were significantly lower after eSET (7334 euro) compared with DET (10,924 euro).
      The ICER of DET compared with eSET was 19,096 euro, meaning that each additional
      successful pregnancy in the DET group will cost 19,096 euro extra. CONCLUSIONS:
      One cycle eSET was less expensive, but also less effective compared to one cycle
      DET. It depends on the society's willingness to pay for one extra successful
      pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of
      view.

PMID- 16613887
TI  - Mutational analysis of the betaglycan gene-coding region in susceptibility for
      ovarian failure.
AB  - BACKGROUND: Elevation of FSH is frequently a consequence of impaired ovarian
      follicle growth. Down-regulation of the FSH levels by inhibins is mediated
      through its receptor betaglycan in the gonadotrophs. Understanding of germline
      status of the betaglycan gene (TGFBR3) is essential for ovarian failure
      pathophysiology. METHODS: Sequence analysis was performed for the coding region
      of TGFBR3 gene in a cohort of 196 ovarian failure cases that include 133
      premature ovarian failure (POF) cases, 63 primary amenorrhoea (PA) cases compared
      with 200 controls. RESULTS: Forty-six variants including six novel exonic
      variants and 16 novel intronic variants were revealed. Two variants were
      missense: (i) p.Iso184Val in a control and (ii) p.Pro775Ser in a POF case.
      Genotypic distribution of three variants (c.382-81C>T, c.382-77T>C and c.1200G>A)
      was significantly different in the patients as compared with the controls. Five
      variants c.382-81C>T, c.382-77T>C, c.566-216G>A, c.1200G>A and c.2022T>C were
      chosen for haplotyping. The CCAAT haplotype was significantly higher in the
      patient population as compared with the controls (P = 0.00007). CONCLUSION: This
      study establishes the first mutational report of the TGFBR3 gene in correlation
      with ovarian failure. Significant diversity of genotype distribution and
      haplotype analysis suggested susceptibility of the TGFBR3 gene for ovarian
      failure aetiology.

PMID- 16613888
TI  - Laser-assisted hatching increases pregnancy and implantation rates in
      cryopreserved embryos that were allowed to cleave in vitro after thawing: a
      prospective randomized study.
AB  - BACKGROUND: Cryopreservation of embryos may lead to zona hardening that may
      compromise in vivo hatching and implantation following thawing and transfer.
      Assisted hatching (AH) has been advocated as a means of assisting the natural
      hatching process and enhancing implantation. METHODS: The aim of this study was
      to assess in a prospective randomized manner the effect of laser-assisted
      hatching (LAH) on implantation as well as clinical and multiple pregnancy rates
      (the primary outcome) after the transfer of frozen-thawed embryos. All embryos
      were thawed the day before transfer, and LAH was performed the next day on
      embryos that cleaved. Control group consisted of embryos that were transferred
      without AH. RESULTS: The performance of LAH significantly increased implantation
      (9.9 versus 20.1%, P < 0.01), clinical pregnancy (27.3 versus 40.9, P < 0.05) and
      multiple pregnancy rates (16 versus 40.3%, P < 0.07). In the LAH group,
      significantly more excess embryos that were left in culture hatched in vitro.
      CONCLUSIONS: LAH improves the outcome of frozen-thawed embryo transfer when
      performed before transfer on embryos that were allowed to cleave.

PMID- 16613889
TI  - Risks of miscarriage and early preterm birth in trichorionic triplet pregnancies
      with embryo reduction versus expectant management: new data and systematic
      review.
AB  - BACKGROUND: Triplet pregnancies are associated with a high risk of miscarriage
      and early preterm birth. It is uncertain if the outcome is improved by embryo
      reduction (ER). METHODS: We examined trichorionic triplet pregnancies with three
      live fetuses at 10-14 weeks of gestation that were managed expectantly or by ER.
      The two groups were compared for the rates of miscarriage, defined as pregnancy
      loss before 24 weeks, and preterm delivery prior to 32 weeks. In addition,
      systematic searches were performed to identify studies comparing outcomes in
      expectant management versus ER in triplet pregnancies. RESULTS: We combined data
      from 365 pregnancies managed in our centre with those of five previous studies.
      In total there were 893 pregnancies. In the ER group (n=482) compared to the
      expectantly managed group (n=411), the rate of miscarriage was higher [8.1 versus
      4.4%; relative risk (RR)=1.83, 95% confidence interval (CI)=1.08-3.16, P=0.036]
      and the rate of early preterm delivery was lower (10.4 versus 26.7%, RR=0.37, 95%
      CI=0.27-0.51, P<0.0001). It was calculated that seven (95% CI=5-9) reductions
      needed to be performed to prevent one early preterm delivery, while the number of
      reductions that would cause one miscarriage was 26 (95% CI=14-193). CONCLUSIONS:
      In trichorionic triplets, ER to twins is associated with an increase in the risk
      of subsequent miscarriage and decrease in risk of early preterm birth.

PMID- 16613890
TI  - A novel selective progesterone receptor modulator asoprisnil (J867) down
      regulates the expression of EGF, IGF-I, TGFbeta3 and their receptors in cultured
      uterine leiomyoma cells.
AB  - BACKGROUND: This study was conducted to evaluate the effects of a novel selective
      progesterone receptor modulator (SPRM) asoprisnil on the expression of growth
      factors and their receptors and on growth factor-induced proliferation of
      cultured uterine leiomyoma and matching myometrial cells. METHODS: The expression
      of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I) and
      transforming growth factor (TGFbeta3) was assessed by immunocytochemistry and
      semi-quantitative RT-PCR. The expression of phosphorylated EGF receptor (p-EGFR),
      IGF-I receptor alpha subunit (IGF-IRalpha) and phosphorylated TGFbeta receptor
      type II (p-TGFbeta RII) was assessed by Western blot analysis. Cell proliferation
      was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4
      sulfophenyl)-2H-tetrazolium assay. RESULTS: Treatment with 10(-7) M asoprisnil
      decreased EGF, IGF-I and TGFbeta3 mRNA and protein expression as well as p-EGFR,
      IGF-IRalpha and p-TGFbeta RII protein expression in leiomyoma cells cultured for
      72 h. EGF (100 ng/ml), IGF-I (100 ng/ml) and TGFbeta3 (10 ng/ml) increased the
      number of viable leiomyoma cells cultured for 72 h, whereas the concomitant
      treatment with 10(-7) M asoprisnil antagonized the growth factor-induced increase
      in leiomyoma cell proliferation. In cultured myometrial cells, however,
      asoprisnil affected neither the growth factor and their receptor expression nor
      the cell proliferation. CONCLUSION: Asoprisnil inhibits the expression of EGF,
      IGF-I, TGFbeta3 and their receptors in cultured leiomyoma cells without affecting
      their expressions in myometrial cells.

PMID- 16613891
TI  - Homeobox gene ESX1L expression is decreased in human pre-term idiopathic fetal
      growth restriction.
AB  - Fetal growth restriction (FGR) is a clinically significant pregnancy disorder in
      which the fetus fails to achieve its full growth potential in utero. This study
      involved idiopathic FGR, which is frequently associated with placental
      dysfunction. Here, we investigated mRNA levels of the human placental homeobox
      gene ESX1L in pre-term and term idiopathic FGR pregnancies compared with
      gestation-matched controls. Real-time PCR quantitation showed ESX1L levels in
      control placentae decreased between pre-term and term [0.7 +/- 0.20 (27-35 weeks,
      n = 13) versus 0.2 +/- 0.06 (36-41 weeks, n = 12), t-test, P < 0.005]. ESX1L
      levels in FGR-affected placentae were significantly lower than in gestation
      matched controls, and there was no significant change between pre-term FGR and
      term FGR [0.32 +/- 0.04 (27-36 weeks, n = 11) versus 0.31 +/- 0.02 (36-41 weeks,
      n = 14), t-test, P = 0.82]. Multiple linear regression analysis revealed a rapid
      decline in ESX1L expression in control placentae [0.075-fold of the calibrator
      for each week of gestation (95% CI = -0.105 to -0.045, P < 0.0005)]. In FGR
      affected placentae, ESX1L levels were lower than in gestation-matched controls,
      and the decline in ESX1L levels with gestation was not significant [0.001-fold of
      the calibrator for each week of gestation (95% CI = -0.030 to 0.010, P < 0.3].
      The linear relationship between ESX1L mRNA levels in FGR-affected placentae and
      gestation-matched controls during gestation was significantly different
      (likelihood ratio test for interaction, P = 0.0005). Our findings were consistent
      with a potential role for the ESX1L gene within the growth control mechanism of
      the fetus, through its effect on placental function.

PMID- 16613892
TI  - Neuromyotonia and limbic encephalitis sera target mature Shaker-type K+ channels:
      subunit specificity correlates with clinical manifestations.
AB  - Autoantibodies to Shaker-type (Kv1) K+ channels are now known to be associated
      with three syndromes. Peripheral nerve hyperexcitability is the chief
      manifestation of acquired neuromyotonia; the combination of neuromyotonia with
      autonomic and CNS involvement is called Morvan's syndrome (MoS); and CNS
      manifestations without peripheral involvement is called limbic encephalitis (LE).
      To determine the cellular basis of these clinical manifestations, we
      immunostained mouse neural tissues with sera from patients with neuromyotonia (n
      = 10), MoS (n = 2) or LE (n = 5), comparing with specific antibodies to relevant
      K+ channel subunits. Fourteen of 17 patients' sera were positive for Kv1.1, Kv1.2
      or Kv1.6 antibodies by immunoprecipitation of 125I-alpha-dendrotoxin-labelled
      rabbit brain K+ channels. Most sera (11 out of 17) labelled juxtaparanodes of
      peripheral myelinated axons, co-localizing with Kv1.1 and Kv1.2. In the CNS, all
      sera tested (n = 12) co-localized with one or more areas of high Kv1.1, Kv1.2 or
      Kv1.6 channel expression: 10 out of 12 sera co-localized with Kv1.1 and Kv1.2 at
      spinal cord juxtaparanodes or cerebellar layers, while 3 out of 12 sera co
      localized additionally (n = 2) or exclusively (n = 1) with Kv1.6 subunits in
      Purkinje cells, motor and hippocampal neurons. However, only sera from LE
      patients labelled the hippocampal areas that are enriched in excitatory, Kv1.1
      positive axon terminals. All sera (17 out of 17) labelled one or more of these
      Kv1 subunits when expressed at the cell membrane of transfected HeLa cells, but
      not when they were retained in the endoplasmic reticulum. Again, LE sera labelled
      Kv1.1 subunits more prominently than did MoS or neuromyotonia sera, suggesting an
      association between higher Kv1.1 specificity and limbic manifestations. In
      contrast, neuromyotonia sera bound more strongly to Kv1.2 subunits than to Kv1.1
      or Kv1.6. These studies support the hypothesis that antibodies to mature surface
      membrane-expressed Shaker-type K+ channels cause acquired neuromyotonia, MoS and
      LE, and suggest that future assays based on immunofluorescence of cells
      expressing individual Kv1 subunits will prove more sensitive than the
      immunoprecipitation assay. Although more than one type of antibody is often
      detectable in individual sera, higher affinity for certain subunits or subunit
      combinations may determine the range of clinical manifestations.

PMID- 16613893
TI  - Molecular pathogenesis of spinocerebellar ataxias.
AB  - The autosomal dominant spinocerebellar ataxias (SCAs) are a group of
      neurodegenerative diseases, clinically and genetically heterogeneous,
      characterized by loss of balance and motor coordination due to dysfunction of the
      cerebellum and its afferent and efferent connections. Despite a well-described
      clinical and pathological phenotype, the molecular and cellular events that
      underlie neurodegeneration are still poorly understood. Compelling evidence
      points to major aetiological roles for interference with transcriptional
      regulation, protein aggregation and clearance, the ubiquitin-proteasome system
      and alterations of calcium homeostasis in the neuronal loss observed during the
      neurodegenerative process. But novel molecular routes that might be disrupted
      during disease progression are also being identified. These pathways could act
      independently or, more likely, interact and enhance each other, triggering the
      accumulation of cellular damage that eventually leads to dysfunction and,
      ultimately, the demise of neurons through a series of multiple events. This
      suggests that simultaneous targeting of several pathways might be therapeutically
      necessary to prevent neurodegeneration and preserve neuronal function.
      Understanding how dysregulation of these pathways mediates disease progression is
      leading to the establishment of effective therapeutic strategies in vivo, which
      may prove beneficial in the treatment of SCAs. Herein, we review the latest
      evidence for the proposed molecular processes to the pathogenesis of dominantly
      inherited spinocerebellar ataxias and the current therapeutic strategies.

PMID- 16613894
TI  - Schwann cell-derived factor-induced modulation of the NgR/p75NTR/EGFR axis
      disinhibits axon growth through CNS myelin in vivo and in vitro.
AB  - When associated with the Nogo receptor (NgR), the transmembrane receptor p75NTR
      signals growth cone collapse. Arrest of CNS axon growth in vivo is mediated by
      CNS myelin-derived inhibitory ligands through either an unknown pathway after NgR
      and Ca2+-dependent activation of the epidermal growth factor receptor (EGFR),
      and/or sequential Rho-A/ROCK/LIM-kinase/cofilin phosphorylation leading to actin
      depolymerization. Paradoxically, rat retinal ganglion cell (RGC) axons regenerate
      through the CNS myelin-rich transected optic nerve after intravitreal sciatic
      nerve grafting without inhibitory ligand neutralization. Here, we show that optic
      nerve regeneration in vivo correlates with Schwann cell-derived factor-induced
      cleavage of NgR and Nogo-A, and inactivation of p75NTR signalling by the
      induction of regulated intramembranous proteolysis (RIP) and the release of both
      extracellular (p75ECD) and intracellular (p75ICD) domains. Hence, Schwann cell
      derived factors compromise inhibitory signalling by (i) antagonizing ligand/NgR
      binding with metalloproteinase-cleaved Nogo-A peptides; (ii) RIP of p75NTR; (iii)
      competitively blocking NgR/p75NTR clustering with soluble p75ECD; and (iv)
      consequent reduced downstream EGFR phosphorylation and suppression of Rho-A
      activation. Moreover, in RGC cultures, exogenous tumour necrosis- converting
      enzyme (TACE) initiates RIP of p75NTR, reduces EGFR phosphorylation, suppresses
      activation of Rho-A, cleaves the ECD from both NgR and TROY, and disinhibits
      neurotrophic factor (NTF) stimulated RGC neurite outgrowth in the presence of CNS
      myelin. Soluble NgRECD binds all CNS myelin-derived ligands and thus has the
      potential to act as an inhibitory signalling antagonist, but the role of TROY and
      its shed ectodomain in growth cone mobility is unknown. siRNA knockdown of p75NTR
      also inactivates Rho-A and disinhibits NTF-stimulated RGC neurite outgrowth in
      cultures with added CNS myelin. In all the above experimental paradigms, Schwann
      cell-derived factor/NTF-induced attenuation of NgR/p75NTR signalling suppresses
      EGFR activation, thereby potentiating axon growth disinhibition.

PMID- 16613896
TI  - Treatment of portal vein tumor thrombosis of hepatoma patients with either
      stereotactic radiotherapy or three-dimensional conformal radiotherapy.
AB  - BACKGROUND: Patients with hepatocellular carcinoma (HCC) often have unresectable
      tumors. Transcatheter arterial chemoembolization (TACE) is one of the limited
      alternative treatments that can prolong these patients' survival. However, the
      presence of portal vein tumor thrombosis (PVTT) is a contraindication for TACE
      and, therefore, HCC patients with PVTT would be depleted of the advantage of
      TACE. The purpose of this study was to analyze the recanalization rate of
      thrombosed portal vein and treatment toxicities after stereotactic radiotherapy
      (SRT) or three-dimensional conformal radiotherapy (3DCRT). METHODS: From March
      2002 to November 2004, 43 patients were enrolled in this prospective study.
      Twenty-two patients were in the SRT group and 21 in the 3DCRT group. For SRT, 3
      Gy per fraction, 3 fractions per week, was given to a total dose of 45 Gy. For
      3DCRT, a daily dose of 1.8 Gy, 5 fractions per week, was given to a total dose of
      45 Gy. RESULTS: Of the 43 patients, 16 completed the planned radiotherapy.
      Eventually, 14 patients received evaluation for portal vein recanalization, 8 in
      the SRT and 6 in the 3DCRT group, respectively. For all patients, the crude
      response rate was 26%. For 14 evaluable patients, the crude response rate was
      79%. It was 75% in the SRT group and 83% in the 3DCRT group (P = 0.71). The
      median survival time was 6.0 and 6.7 months for the SRT and 3DCRT group,
      respectively (P = 0.911). CONCLUSIONS: Image-based radiotherapy, either SRT or
      3DCRT, can recanalize the PVTT in unresectable HCC patients. Responders also had
      better 1 year and 2 year survivals. A more strict patient selection criterion may
      maximize the potential benefits of radiotherapy for hepatoma patients with PVTT.

PMID- 16613895
TI  - Clinicopathological and imaging correlates of progressive aphasia and apraxia of
      speech.
AB  - Apraxia of speech (AOS) is a motor speech disorder characterized by slow speaking
      rate, abnormal prosody and distorted sound substitutions, additions, repetitions
      and prolongations, sometimes accompanied by groping, and trial and error
      articulatory movements. Although AOS is frequently subsumed under the heading of
      aphasia, and indeed most often co-occurs with aphasia, it can be the predominant
      or even the sole manifestation of a degenerative neurological disease. In this
      study we determine whether the clinical classifications of aphasia and AOS
      correlated with pathological diagnoses and specific biochemical and anatomical
      structural abnormalities. Seventeen cases with initial diagnoses of a
      degenerative aphasia or AOS were re-classified independently by two speech
      language pathologists--blinded to pathological and biochemical findings--into one
      of five operationally defined categories of aphasia and AOS. Pathological
      diagnoses in the 17 cases were progressive supranuclear palsy in 6, corticobasal
      degeneration in 5, frontotemporal lobar degeneration with ubiquitin-only
      immunoreactive changes in 5 and Pick's disease in 1. Magnetic resonance imaging
      analysis using voxel-based morphometry (VBM), and single photon emission
      tomography were completed, blinded to the clinical diagnoses, and clinicoimaging
      and clinicopathological associations were then sought. Interjudge clinical
      classification reliability was 87% (kappa = 0.8) for all evaluations. Eleven
      cases had evidence of AOS, of which all (100%) had a pathological diagnosis
      characterized by underlying tau biochemistry, while five of the other six cases
      without AOS did not have tau biochemistry (P = 0.001). A majority of the 17 cases
      had more than one yearly evaluation, demonstrating the evolution of the speech
      and language syndromes, as well as motor signs. VBM revealed the premotor and
      supplemental motor cortices to be the main cortical regions associated with AOS,
      while the anterior peri-sylvian region was associated with non-fluent aphasia.
      Refining the classification of the degenerative aphasias and AOS may be necessary
      to improve our understanding of the relationships among behavioural, pathological
      and imaging correlations.

PMID- 16613897
TI  - Progressive alterations in the hypothalamic-pituitary-adrenal axis in the R6/2
      transgenic mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is characterized by a triad of motor, psychiatric and
      cognitive symptoms. Although many of these symptoms are likely to be related to
      central nervous system pathology, others may be due to changes in peripheral
      tissues. The R6/2 mouse, a transgenic model of HD expressing exon 1 of the human
      HD gene, develops progressive alterations in the hypothalamic-pituitary-adrenal
      axis, reminiscent of a Cushing-like syndrome. We observed muscular atrophy,
      reduced bone mineral density, abdominal fat accumulation and insulin resistance
      in the mice. All these changes could be consequences of increased glucocorticoid
      levels. Indeed, hypertrophy of the adrenal cortex and a progressive increase in
      serum and urine corticosterone levels were found in R6/2 mice. In addition, the
      intermediate pituitary lobe was markedly enlarged and circulating adreno
      corticotrophic hormone (ACTH) increased. Under normal conditions dopamine
      represses the ACTH expression. In the R6/2 mice, however, the expression of
      pituitary dopamine D2 receptors was reduced by half, possibly explaining the
      increase in ACTH. Urinary samples from 82 HD patients and 68 control subjects
      were analysed for cortisol: in accord with the observations in the R6/2 mice,
      urinary cortisol increased in parallel with disease progression. This progressive
      increase in cortisol may contribute to the clinical symptoms, such as muscular
      wasting, mood changes and some of the cognitive deficits that occur in HD.

PMID- 16613898
TI  - Suppression of disease phenotypes of adult mito-mice carrying pathogenic mtDNA by
      bone marrow transplantation.
AB  - For directly addressing the issue of gene therapy of adult patients with
      mitochondrial diseases, we carried out bone marrow transplantation to adult mito
      mice with mutated mtDNA and expressing respiration defects for improvement of
      disease phenotypes. We supposed that bone marrow cells transdifferentiated into
      various tissues, so that their transplantation would suppress disease phenotypes.
      The results showed improvement of survival and delayed expression of renal
      failure. As most mito-mice without a transplant died due to renal failure, we
      examined whether transplanted bone marrow cells transdifferentiated into renal
      tissues carrying improved renal function. Histochemical analyses showed that the
      suppression of disease phenotypes was not due to transdifferentiation, but due to
      suppression of apoptosis of renal cells. Thus, bone marrow cells possess a novel
      function of supporting tissues by suppressing apoptosis induced by respiration
      defects.

PMID- 16613899
TI  - A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8)
      causes neonatal diabetes.
AB  - Neonatal diabetes is a genetically heterogeneous disorder with nine different
      genetic aetiologies reported to date. Heterozygous activating mutations in the
      KCNJ11 gene encoding Kir6.2, the pore-forming subunit of the ATP-sensitive
      potassium (K(ATP)) channel, are the most common cause of permanent neonatal
      diabetes. The sulphonylurea receptor (SUR) SUR1 serves as the regulatory subunit
      of the K(ATP) channel in pancreatic beta cells. We therefore hypothesized that
      activating mutations in the ABCC8 gene, which encodes SUR1, might cause neonatal
      diabetes. We identified a novel heterozygous mutation, F132L, in the ABCC8 gene
      of a patient with severe developmental delay, epilepsy and neonatal diabetes
      (DEND syndrome). This mutation had arisen de novo and was not present in 150
      control chromosomes. Residue F132 shows evolutionary conservation across species
      and is located in the first set of transmembrane helices (TMD0) of SUR1, which is
      proposed to interact with Kir6.2. Functional studies of recombinant K(ATP)
      channels demonstrated that F132L markedly reduces the sensitivity of the K(ATP)
      channel to inhibition by MgATP and this increases the whole-cell K(ATP) current.
      The functional consequence of this ABCC8 mutation mirrors that of KCNJ11
      mutations causing neonatal diabetes and provides new insights into the
      interaction of Kir6.2 and SUR1. As SUR1 is expressed in neurones as well as in
      beta cells, this mutation can account for both neonatal diabetes and the
      neurological phenotype. Our results demonstrate that SUR1 mutations constitute a
      new genetic aetiology for neonatal diabetes and that they act by reducing the
      K(ATP) channel's ATP sensitivity.

PMID- 16613900
TI  - Identification of cis-regulatory elements for MECP2 expression.
AB  - Rett syndrome (RTT) is an X-linked dominant disabling neurodevelopmental disorder
      caused by loss of function mutations in the MECP2 gene, located at Xq28, which
      encodes a multifunctional protein. MECP2 expression is regulated in a
      developmental stage and cell-type-specific manner. The need for tightly
      controlled MeCP2 levels in brain is strongly suggested by neurologically abnormal
      phenotypes of mouse models with mild overexpression and by mental retardation in
      human males with MECP2 duplication. We set out to identify long-range cis
      regulatory sequences that differentially regulate MECP2 transcription and, when
      mutated, may contribute to the pathogenesis of RTT, autism or X-linked mental
      retardation. By inter-species sequence comparisons, we detected 27 highly
      conserved non-coding DNA sequences within a 210 kb region covering MECP2. We
      functionally confirmed four enhancer and two silencer elements by performing
      luciferase reporter assays in four different human cell lines. The transcription
      factor binding capability of the identified regulatory elements was tested by gel
      shift assays. To locate the human MECP2 core promoter, we dissected the promoter
      region by reporter assays with deletion constructs. We then used chromosome
      conformation capture methods to document long-range interactions of three
      enhancers and two silencers with the MECP2 promoter. Acting over distances of up
      to 130 kb, these elements may influence chromatin configurations and regulate
      MECP2 transcription. Our study has defined the "MECP2 functional expression
      module" and identified enhancer and silencer elements that are likely to be
      responsible for the tissue-specific, developmental stage-specific or splice
      variant-specific control of MeCP2 protein expression.

PMID- 16613901
TI  - Mitochondrial localization of telomerase as a determinant for hydrogen peroxide
      induced mitochondrial DNA damage and apoptosis.
AB  - We have previously shown that the protein subunit of telomerase, hTERT, has a
      bonafide N-terminal mitochondrial targeting sequence, and that ectopic hTERT
      expression in human cells correlated with increase in mtDNA damage after hydrogen
      peroxide treatment. In this study, we show, using a loxP hTERT construct, that
      this increase in mtDNA damage following hydrogen peroxide exposure is dependent
      on the presence of hTERT itself. Further experiments using a dominant negative
      hTERT mutant shows that telomerase must be catalytically active to mediate the
      increase in mtDNA damage. Etoposide, but not methylmethanesulfate, also promotes
      mtDNA lesions in cells expressing active hTERT, indicating genotoxic specificity
      in this response. Fibroblasts expressing hTERT not only show a approximately 2
      fold increase in mtDNA damage after oxidative stress but also suffer a 10-30-fold
      increase in apoptotic cell death as assayed by Annexin-V staining, caspase-3
      activation and PARP cleavage. Mutations to the N-terminal mitochondrial leader
      sequence causes a complete loss of mitochondrial targeting without affecting
      catalytic activity. Cells carrying this mutated hTERT not only have significantly
      reduced levels of mtDNA damage following hydrogen peroxide treatment, but
      strikingly also do not shown any loss of viability or cell growth. Thus,
      localization of hTERT to the mitochondria renders cells more susceptible to
      oxidative stress-induced mtDNA damage and subsequent cell death, whereas nuclear
      targeted hTERT, in the absence of mitochondrial localization, is associated with
      diminished mtDNA damage, increased cell survival and protection against cellular
      senescence.

PMID- 16613902
TI  - Demography of the invasive geophyte Oxalis pes-caprae across a Mediterranean
      island.
AB  - BACKGROUND AND AIMS: Success during the early stages of the life-history of alien
      plants is essential for invasion to occur. The reproductive components of plant
      invaders have mostly been studied in species reproducing sexually but little is
      known about invaders that depend exclusively on vegetative reproduction. In this
      paper, the importance of the different recruitment stages on population growth is
      quantified and, thus, the invasion potential of the South African annual geophyte
      Oxalis pes-caprae invading Mediterranean ecosystems is assessed. METHODS: Tests
      and experiments were conducted across Menorca (Balearic Islands) to analyse the
      spatial variability of Oxalis pes-caprae reproductive components (i.e. bulb
      production, bulb bank, bulb predation, bulb mortality, bulb dormancy, bulb
      germination, plant establishment and survival). KEY RESULTS: Oxalis pes-caprae
      has a transient bulb bank that remains dormant in the soil during summer. High
      levels of bulb predation after dispersal, followed by bulb mortality during
      summer or a failure to germinate in autumn were the most critical factors
      limiting plant establishment. Bulb germination was high. However, plant
      establishment and bulb production is constrained by intraspecific competition,
      but is not affected by soil disturbance. No symptoms of spatial discordance could
      be found between recruitment stages because the spatial variability of the life
      cycle was extremely low at all the scales examined (i.e. among populations,
      habitats and microsites). It was estimated that, on average, 4 % of bulbs can
      become plants the following year and the field rate of population increase
      (lambda) to be 0.08. CONCLUSIONS: The results suggest that invasion is
      constrained by post-dispersal bulb predation, loss of viability of the propagule
      bank due to summer drought and high intraspecific competition. However, a high
      spatial concordance between recruitment stages and probably a high propagule
      pressure due to human and livestock bulb dispersal determine the success of this
      invader across Menorca Island.

PMID- 16613903
TI  - Charting the isophasic endophyte of dwarf mistletoe Arceuthobium douglasii
      (Viscaceae) in host apical buds.
AB  - BACKGROUND AND AIMS: Dwarf mistletoes (Arceuthobium; Viscaceae) are highly
      specialized dioecious angiosperms parasitic on many gymnosperm hosts in the
      northern hemisphere. Several dwarf mistletoe species are capable of inducing an
      unusual form of isophasic infection in which the internal (endophytic) system
      proliferates even into the apical buds of its hosts. Studies of the internal
      endophytic system have, for the most part, focused on the parasite within
      secondary host tissues. The present anatomical and ultrastructural study
      characterizes the growth pattern of the isophasic endophytic system of
      Arceuthobium douglasii within the dormant apical buds of Pseudotsuga menziesii.
      METHODS: Semi-thin serial sections from dwarf mistletoe-infected host apical buds
      were mounted, stained and micrographed. Graphic files were created from the
      serial micrographs and these files were stacked. These stacked files were
      utilized to describe the pattern of growth of the endophyte within the host
      tissue. The interface between cells of the mistletoe and host was also examined
      at the ultrastructural level by transmission electron microscopy. KEY RESULTS: By
      utilizing a novel technique of superimposed graphics, the current study reveals
      an organized pattern of mistletoe distribution that penetrates further into host
      tissues than previously known. A consistent pattern of growth occurring even into
      the preformed leaves of the host is documented. CONCLUSIONS: The apparently non
      intrusive growth of the parasite appears to be developmentally synchronized with
      that of the host. No symplastic connections were observed in the ultrastructural
      examination of the parasite/host interface within the apical buds of Pseudotsuga
      menziesii parasitized by A. douglasii or of Pinus contorta parasitized by A.
      americanum.

PMID- 16613904
TI  - Effect of local heating and cooling on cambial activity and cell differentiation
      in the stem of Norway spruce (Picea abies).
AB  - BACKGROUND AND AIMS The effect of heating and cooling on cambial activity and
      cell differentiation in part of the stem of Norway spruce (Picea abies) was
      investigated. METHODS: A heating experiment (23-25 degrees C) was carried out in
      spring, before normal reactivation of the cambium, and cooling (9-11 degrees C)
      at the height of cambial activity in summer. The cambium, xylem and phloem were
      investigated by means of light- and transmission electron microscopy and UV
      microspectrophotometry in tissues sampled from living trees. KEY RESULTS:
      Localized heating for 10 d initiated cambial divisions on the phloem side and
      after 20 d also on the xylem side. In a control tree, regular cambial activity
      started after 30 d. In the heat-treated sample, up to 15 earlywood cells
      undergoing differentiation were found to be present. The response of the cambium
      to stem cooling was less pronounced, and no anatomical differences were detected
      between the control and cool-treated samples after 10 or 20 d. After 30 d,
      latewood started to form in the sample exposed to cooling. In addition, almost no
      radially expanding tracheids were observed and the cambium consisted of only five
      layers of cells. Low temperatures reduced cambial activity, as indicated by the
      decreased proportion of latewood. On the phloem side, no alterations were
      observed among cool-treated and non-treated samples. CONCLUSIONS: Heating and
      cooling can influence cambial activity and cell differentiation in Norway spruce.
      However, at the ultrastructural and topochemical levels, no changes were observed
      in the pattern of secondary cell-wall formation and lignification or in lignin
      structure, respectively.

PMID- 16613905
TI  - Ribosomal RNA as molecular barcodes: a simple correlation analysis without
      sequence alignment.
AB  - MOTIVATION: We explored the feasibility of using unaligned rRNA gene sequences as
      DNA barcodes, based on correlation analysis of composition vectors (CVs) derived
      from nucleotide strings. We tested this method with seven rRNA (including 12, 16,
      18, 26 and 28S) datasets from a wide variety of organisms (from archaea to
      tetrapods) at taxonomic levels ranging from class to species. RESULT: Our results
      indicate that grouping of taxa based on CV analysis is always in good agreement
      with the phylogenetic trees generated by traditional approaches, although in some
      cases the relationships among the higher systemic groups may differ. The
      effectiveness of our analysis might be related to the length and divergence among
      sequences in a dataset. Nevertheless, the correct grouping of sequences and
      accurate assignment of unknown taxa make our analysis a reliable and convenient
      approach in analyzing unaligned sequence datasets of various rRNAs for barcoding
      purposes. AVAILABILITY: The newly designed software (CVTree 1.0) is publicly
      available at the Composition Vector Tree (CVTree) web server
      http://cvtree.cbi.pku.edu.cn.

PMID- 16613906
TI  - VizStruct for visualization of genome-wide SNP analyses.
AB  - MOTIVATION: The size, dimensionality and the limited range of the data values
      make visualization of single nucleotide polymorphism (SNP) datasets challenging.
      The purpose of this study is to evaluate the usefulness of 3D VizStruct, a novel
      multi-dimensional data visualization technique for analyzing patterns in SNP
      datasets. RESULTS: VizStruct is an interactive visualization technique that
      reduces multi-dimensional data to two dimensions using the complex-valued
      harmonics of the discrete Fourier transform (DFT). In the 3D VizStruct extension,
      the multi-dimensional SNP data vectors are reduced to three dimensions using a
      combination of the DFT and the Kullback-Leibler divergence. The performance of 3D
      VizStruct was challenged with several biologically relevant published datasets
      that included human Chromosome 21, the human lipoprotein lipase (LPL) gene locus
      and the multi-locus genotypes of coral populations. In every case, the 3D
      VizStruct mapping provided an intuitive visual description of the key
      characteristics of the underlying multi-dimensional genotype.

PMID- 16613907
TI  - FlyTF: a systematic review of site-specific transcription factors in the fruit
      fly Drosophila melanogaster.
AB  - SUMMARY: We present a manually annotated catalogue of site-specific transcription
      factors (TFs) in the fruit fly Drosophila melanogaster. These were identified
      from a list of candidate proteins with transcription-related Gene Ontology (Go)
      annotation as well as structural DNA-binding domain assignments. For all 1052
      candidate proteins, a defined set of rules was applied to classify information
      from the literature and computational data sources with respect to both DNA
      binding and transcriptional regulatory properties. We propose a set of 753 TFs in
      the fruit fly, of which 23 are confident novel predictions of this function for
      previously uncharacterized proteins.

PMID- 16613908
TI  - STRAL: progressive alignment of non-coding RNA using base pairing probability
      vectors in quadratic time.
AB  - MOTIVATION: Alignment of RNA has a wide range of applications, for example in
      phylogeny inference, consensus structure prediction and homology searches. Yet
      aligning structural or non-coding RNAs (ncRNAs) correctly is notoriously
      difficult as these RNA sequences may evolve by compensatory mutations, which
      maintain base pairing but destroy sequence homology. Ideally, alignment programs
      would take RNA structure into account. The Sankoff algorithm for the simultaneous
      solution of RNA structure prediction and RNA sequence alignment was proposed 20
      years ago but suffers from its exponential complexity. A number of programs
      implement lightweight versions of the Sankoff algorithm by restricting its
      application to a limited type of structure and/or only pairwise alignment. Thus,
      despite recent advances, the proper alignment of multiple structural RNA
      sequences remains a problem. RESULTS: Here we present StrAl, a heuristic method
      for alignment of ncRNA that reduces sequence-structure alignment to a two
      dimensional problem similar to standard multiple sequence alignment. The scoring
      function takes into account sequence similarity as well as up- and downstream
      pairing probability. To test the robustness of the algorithm and the performance
      of the program, we scored alignments produced by StrAl against a large set of
      published reference alignments. The quality of alignments predicted by StrAl is
      far better than that obtained by standard sequence alignment programs, especially
      when sequence homologies drop below approximately 65%; nevertheless StrAl's
      runtime is comparable to that of ClustalW.

PMID- 16613909
TI  - Improving MHC binding peptide prediction by incorporating binding data of
      auxiliary MHC molecules.
AB  - MOTIVATION: Various computational methods have been proposed to tackle the
      problem of predicting the peptide binding ability for a specific MHC molecule.
      These methods are based on known binding peptide sequences. However, current
      available peptide databases do not have very abundant amounts of examples and are
      highly redundant. Existing studies show that MHC molecules can be classified into
      supertypes in terms of peptide-binding specificities. Therefore, we first give a
      method for reducing the redundancy in a given dataset based on information
      entropy, then present a novel approach for prediction by learning a predictive
      model from a dataset of binders for not only the molecule of interest but also
      for other MHC molecules. RESULTS: We experimented on the HLA-A family with the
      binding nonamers of A1 supertype (HLA-A*0101, A*2601, A*2902, A*3002), A2
      supertype (A*0201, A*0202, A*0203, A*0206, A*6802), A3 supertype (A*0301, A*1101,
      A*3101, A*3301, A*6801) and A24 supertype (A*2301 and A*2402), whose data were
      collected from six publicly available peptide databases and two private sources.
      The results show that our approach significantly improves the prediction accuracy
      of peptides that bind a specific HLA molecule when we combine binding data of HLA
      molecules in the same supertype. Our approach can thus be used to help find new
      binders for MHC molecules.

PMID- 16613910
TI  - Dragon Promoter Mapper (DPM): a Bayesian framework for modelling promoter
      structures.
AB  - Dragon Promoter Mapper (DPM) is a tool to model promoter structure of co
      regulated genes using methodology of Bayesian networks. DPM exploits an
      exhaustive set of motif features (such as motif, its strand, the order of motif
      occurrence and mutual distance between the adjacent motifs) and generates models
      from the target promoter sequences, which may be used to (1) detect regions in a
      genomic sequence which are similar to the target promoters or (2) to classify
      other promoters as similar or not to the target promoter group. DPM can also be
      used for modelling of enhancers and silencers. AVAILABILITY: http://defiant.i2r.a
      star.edu.sg/projects/BayesPromoter/ CONTACT: vlad@sanbi.ac.za SUPPLEMENTARY
      INFORMATION: Manual for using DPM web server is provided at http://defiant.i2r.a
      star.edu.sg/projects/BayesPromoter/html/manual/manual.htm.

PMID- 16613911
TI  - Using hidden Markov models and observed evolution to annotate viral genomes.
AB  - MOTIVATION: ssRNA (single stranded) viral genomes are generally constrained in
      length and utilize overlapping reading frames to maximally exploit the coding
      potential within the genome length restrictions. This overlapping coding
      phenomenon leads to complex evolutionary constraints operating on the genome. In
      regions which code for more than one protein, silent mutations in one reading
      frame generally have a protein coding effect in another. To maximize coding
      flexibility in all reading frames, overlapping regions are often compositionally
      biased towards amino acids which are 6-fold degenerate with respect to the 64
      codon alphabet. Previous methodologies have used this fact in an ad hoc manner to
      look for overlapping genes by motif matching. In this paper differentiated
      nucleotide compositional patterns in overlapping regions are incorporated into a
      probabilistic hidden Markov model (HMM) framework which is used to annotate ssRNA
      viral genomes. This work focuses on single sequence annotation and applies an HMM
      framework to ssRNA viral annotation. A description of how the HMM is
      parameterized, whilst annotating within a missing data framework is given. A
      Phylogenetic HMM (Phylo-HMM) extension, as applied to 14 aligned HIV2 sequences
      is also presented. This evolutionary extension serves as an illustration of the
      potential of the Phylo-HMM framework for ssRNA viral genomic annotation. RESULTS:
      The single sequence annotation procedure (SSA) is applied to 14 different strains
      of the HIV2 virus. Further results on alternative ssRNA viral genomes are
      presented to illustrate more generally the performance of the method. The results
      of the SSA method are encouraging however there is still room for improvement,
      and since there is overwhelming evidence to indicate that comparative methods can
      improve coding sequence (CDS) annotation, the SSA method is extended to a Phylo
      HMM to incorporate evolutionary information. The Phylo-HMM extension is applied
      to the same set of 14 HIV2 sequences which are pre-aligned. The performance
      improvement that results from including the evolutionary information in the
      analysis is illustrated.

PMID- 16613912
TI  - Base excision repair fidelity in normal and cancer cells.
AB  - In mammalian cells, base excision repair (BER) is the major repair pathway
      involved in the removal of non-bulky damaged nucleotides. The fidelity of BER is
      dependent on the polymerization step, where the major BER DNA polymerase (Pol
      beta) must incorporate the correct Watson-Crick base paired nucleotide into the
      one nucleotide repair gap. Recent studies have indicated that expression of some
      Pol beta variants or changes in expression of wild-type Pol beta protein,
      frequently found in cancer cells, can lead to DNA repair synthesis errors and
      confers to cells a mutator phenotype.

PMID- 16613913
TI  - Possible involvement of XPA in repair of oxidative DNA damage deduced from
      analysis of damage, repair and genotype in a human population study.
AB  - Participants in a study of occupational exposure to mineral fibres in Slovakia
      were analysed for the polymorphism 23A-->G in the DNA repair gene XPA. Of the 388
      subjects, 239 were exposed to asbestos, stonewool or glass fibre; the rest were
      unexposed controls. Levels of DNA base alterations (oxidation and alkylation) in
      lymphocytes were measured using the comet assay with lesion-specific
      endonucleases. 8-oxoguanine DNA glycosylase (OGG1) DNA repair activity was
      measured, as incision activity of a lymphocyte extract on DNA containing the OGG1
      substrate 8-oxoguanine. Presence of the A allele was associated with higher
      levels of DNA damage (sites sensitive to formamidopyrimidine DNA glycosylase,
      endonuclease III or 3-methyladenine DNA glycosylase II) as well as with higher
      activity of OGG1 repair enzyme. DNA base damage increased with age, showing
      highly significant correlations when the whole population or subgroups of the
      population were analysed. OGG1 repair activity also increased with age, but when
      analysed according to XPA genotype, the increase was observed only in those
      individuals with an A allele. Although XPA is known as a protein involved in
      nucleotide excision repair of UV-induced damage and bulky DNA adducts, it may
      also have a role in the repair of oxidized bases.

PMID- 16613914
TI  - SMAD4 mutations found in unselected HHT patients.
AB  - BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant
      disease exhibiting multifocal vascular telangiectases and arteriovenous
      malformations. The majority of cases are caused by mutations in either the
      endoglin (ENG) or activin receptor-like kinase 1 (ALK1, ACVRL1) genes; both
      members of the transforming growth factor (TGF)-beta pathway. Mutations in SMAD4,
      another TGF-beta pathway member, are seen in patients with the combined syndrome
      of juvenile polyposis (JP) and HHT (JP-HHT). METHODS: We sought to determine if
      HHT patients without any apparent history of JP, who were undergoing routine
      diagnostic testing, would have mutations in SMAD4. We tested 30 unrelated HHT
      patients, all of whom had been referred for DNA based testing for HHT and were
      found to be negative for mutations in ENG and ALK1. RESULTS: Three of these
      people harboured mutations in SMAD4, a rate of 10% (3/30). The SMAD4 mutations
      were similar to those found in other patients with the JP-HHT syndrome.
      CONCLUSIONS: The identification of SMAD4 mutations in HHT patients without prior
      diagnosis of JP has significant and immediate clinical implications, as these
      people are likely to be at risk of having JP-HHT with the associated increased
      risk of gastrointestinal cancer. We propose that routine DNA based testing for
      HHT should include SMAD4 for samples in which mutations in neither ENG nor ALK1
      are identified. HHT patients with SMAD4 mutations should be screened for colonic
      and gastric polyps associated with JP.

PMID- 16613915
TI  - Undergraduate musculoskeletal examination teaching by trained patient educators-
      a comparison with doctor-led teaching.
AB  - BACKGROUND: To compare the core hand and knee examination skills gained by
      undergraduates taught either by trained patient educators (PEs) or by doctors.
      METHODS: A total of 50 final year medical students were randomized to receive
      training from PEs or doctors. Group A were taught hand examination by a PE with
      rheumatoid arthritis, and knee examination by a PE with osteoarthritis. Group B
      was taught hand and knee examination by a consultant rheumatologist plus an
      untrained patient with appropriate signs. All students were taught an established
      core skills set in small group workshops. Students then undertook two validated
      objective structured clinical examination (OSCE) stations with two blinded
      assessors. Pre- and post-teaching questionnaires established the students' self
      reported levels of skills (SRS) and a student evaluation of teaching (SET). The
      study was analysed as an equivalence trial. A mean difference in OSCE scores of
      10% was assumed to be of educational significance. RESULTS: Although the SET
      scores of both groups were high, the doctor-led group received higher scores.
      Aside from this, the two student groups did not differ significantly. There were
      no significant differences in mean hand OSCE (mean difference = 0.88, P = 0.28,
      95% CI = -0.73 to 2.49) or knee OSCE (mean difference = 0.28, P = 0.7, 95% CI = 
      1.19 to 1.75) scores. Both the upper and lower confidence intervals for each mean
      difference fell within the 10% range (-2.8 to 2.8 for the hand, and -2.5 to 2.5
      for the knee) and equivalence was assumed. CONCLUSIONS: Adequately trained PEs
      can deliver clearly structured undergraduate skills, teaching with equivalent
      learning outcomes to those of rheumatology consultants. PEs are a valuable
      development to augment musculoskeletal education in the face of expanding student
      numbers.

PMID- 16613916
TI  - Illness trajectories in Mexican children with juvenile idiopathic arthritis and
      their parents.
AB  - BACKGROUND: We hypothesize that the qualitative approach of socio-cultural
      aspects in children with juvenile idiopathic arthritis (JIA) and their parents
      would improve the understanding of their illness. OBJECTIVE: To explain the
      phenomenon of experiencing JIA within a specific cultural context. METHODS: The
      theoretical position of this research was based on the substantive theories of
      suffering, explanatory models and illness experience. Its design was that of
      qualitative field, and its analysis followed the interpretative grounded theory
      methodology. Data were collected by in-depth interviews and notes; tape
      recordings were transcribed verbatim, read and imported into the ATLAS/ti 4.2
      software. Data conceptualization, categorization and interpretation were based on
      the constant comparison method. RESULTS: A total of 16 adults and six children
      from 10 families were interviewed. 'Pilgrimage' (metaphorically referred by some
      of the parents) was a major code in the study that reflected the religious
      reference to the trajectory of pain, faith and hope. For children, pilgrimage was
      conformed by immediate concepts; for parents, by historical and immediate
      experiences influenced by JIA subtype. Pilgrimage was consistent with the model
      of the illness trajectory theory, which conceptually relates to the idea that the
      course of chronic diseases is variable and modifiable throughout time.
      CONCLUSION: The qualitative approach of JIA provides wide and deep information on
      the perception that children and parents have about the disease. The illness
      trajectory theory corresponds to pilgrimage, the theoretical model for JIA in
      this study.

PMID- 16613917
TI  - Development of ocular disease in patients with mucous membrane pemphigoid
      involving the oral mucosa.
AB  - AIM: To determine the rate of development of ocular disease in patients
      presenting with mucous membrane pemphigoid (MMP) involving their oral mucosa.
      METHODS: Diagnosis of oral MMP was made on the basis of clinical signs,
      histology, and direct and indirect immunofluorescence. Age, race, sex, age at
      diagnosis, progression of eye signs, duration of follow up, and time to
      progression of ocular disease were recorded. RESULTS: 30 patients with
      established oral MMP were reviewed. The mean age at diagnosis was 65.2 years
      (range 46-84 years) and 16/30 (53%) were male. At initial ocular review nine
      (30%) patients showed ocular signs of pemphigoid, of whom two had mild (IIA
      IIIB), four moderate (IIB IIIC), and three severe (IIC IIID) disease. The mean
      interval between diagnosis of oral MMP and first ophthalmic review was 19.3
      months (range 0-144). Over the period of follow up two (7%) patients developed
      ocular disease at 19 months and 48 months, respectively, despite having had no
      evidence of ocular involvement at presentation. In total, 11 (37%) patients with
      oral disease eventually showed ocular disease with a calculated incidence rate
      for the development of ocular disease of 0.03 per person year over 5 years.
      CONCLUSIONS: MMP may affect different tissues at different stages, often
      separated by many years. Patients with MMP involving their oral mucosa are at
      significant risk of developing ocular disease and should remain under ophthalmic
      review.

PMID- 16613918
TI  - Endothelial cell proliferation in the choriocapillaris during human retinal
      differentiation.
AB  - BACKGROUND: Differentiation patterns of the neural retina and its retinal
      vasculature are not well matched. The foveal region differentiates first, however
      the central retina is not vascularised until late in gestation. The authors
      explored the hypothesis that higher rates of endothelial cell proliferation in
      the choriocapillaris of the central retina might compensate for the slow growth
      of central retinal vessels, providing supplementary nutrients to the region
      during the early stages of neuronal maturation. METHODS: Frozen sections of five
      human fetal eyes (14-18.5 weeks' gestation), were examined for Ki-67 and CD34
      immunoreactivity using confocal microscopy. Measurements of choriocapillaris area
      and the number of proliferating choroidal endothelial cells were used to
      calculate the rate of choroidal endothelial proliferation at five different
      chorioretinal locations. RESULTS: The choriocapillaris area is consistently
      greater in the foveal region than at other locations and increases progressively
      with age. A higher rate of endothelial cell proliferation was found in parts of
      the choriocapillaris associated with the undifferentiated (proliferating) neural
      retina, compared with the differentiated, central region. CONCLUSION: The
      findings suggest that mechanisms regulating proliferation and growth of the
      choroidal vasculature are independent of differentiation in the neural retina,
      and are thus profoundly different from mechanisms that regulate formation of the
      retinal vasculature.

PMID- 16613919
TI  - Remote image based retinopathy of prematurity diagnosis: a receiver operating
      characteristic analysis of accuracy.
AB  - BACKGROUND/AIMS: Telemedicine offers potential to improve the accessibility and
      quality of diagnosis of retinopathy of prematurity (ROP). The aim of this study
      was to measure accuracy of remote image based ROP diagnosis by three readers
      using receiver operating characteristic (ROC) analysis. METHODS: 64 hospitalised
      infants who met ROP examination criteria underwent two consecutive bedside
      procedures: dilated examination by an experienced paediatric ophthalmologist and
      digital retinal imaging with a commercially available wide angle camera. 410
      images from 163 eyes were reviewed independently by three trained ophthalmologist
      readers, who classified each eye into one of four categories: no ROP, mild ROP,
      type 2 prethreshold ROP, or ROP requiring treatment. Sensitivity and specificity
      for detection of mild or worse ROP, type 2 prethreshold or worse ROP, and ROP
      requiring treatment were determined, compared to a reference standard of dilated
      ophthalmoscopy. ROC curves were generated by calculating values for each reader
      at three diagnostic cut-off levels: mild or worse ROP (that is, reader was asked
      whether image sets represented mild or worse ROP), type 2 prethreshold or worse
      ROP (that is, reader was asked whether image sets represented type 2 prethreshold
      or worse ROP), and ROP requiring treatment. RESULTS: Areas under ROC curves
      ranged from 0.747-0.896 for detection of mild or worse ROP, 0.905-0.946 for
      detection of type 2 prethreshold or worse ROP, and 0.941-0.968 for detection of
      ROP requiring treatment. CONCLUSIONS: Remote interpretation is highly accurate
      among multiple readers for the detection of ROP requiring treatment, but less so
      for detection of mild or worse ROP.

PMID- 16613920
TI  - Short term oral minocycline treatment of meibomianitis.
AB  - AIM: To evaluate the clinical impact, aqueous tear parameters, and meibomian
      gland morphology in patients with primary meibomianitis before, during, and 3
      months after a course of oral minocycline. METHODS: 16 patients were
      prospectively enrolled, 11 male and five female (mean age 69 years old). Each
      patient received routine clinical evaluations before, after 3 months therapy, and
      at 6 month study follow up visit. The clinical appearance, tear volume, flow and
      turnover, evaporation, Schirmer I test, meibomian gland dropout, lissamine green
      staining, and bacteriology wer evaluated. RESULTS: Improvement was observed in
      clinical signs of meibomianitis at the second and third visits. Microbial culture
      findings improved. Decreased aqueous tear volume and flow, and increased
      evaporation rate range at 35-45% relative humidity (RH) (p < 0.05) were also
      detected. Other related tear parameters did not change. Meibomian gland dropout
      showed no improvement. CONCLUSIONS: 3 months of oral minocycline resulted in
      clinical improvements in all meibomianitis signs that persisted for at least 3
      months after discontinuation despite decreased aqueous tear volume and flow with
      increased evaporation (35-45% RH). However, there was improvement in the
      turbidity of secretions. Short term minocycline therapy probably has efficacy in
      the management of meibomianitis that extends beyond eradication of bacteria.

PMID- 16613921
TI  - Adenosine A2A receptor mediated protective effect of 2-(6-cyano-1-hexyn-1
      yl)adenosine on retinal ischaemia/reperfusion damage in rats.
AB  - AIMS: To determine the effect of 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado), an
      adenosine A2A receptor agonist, on retinal ischaemia/reperfusion damage in rats.
      METHODS: Retinal ischaemia/reperfusion damage was induced by elevating the
      intraocular pressure of one eye to 130 mm Hg for 60 minutes and returning it to
      normal. 7 days later, retinal ischaemia/reperfusion damage was histologically
      quantified by measuring the thickness of retinal layers. Intraocular pressure was
      measured by pressure transducer. RESULTS: Retinal ischaemia/reperfusion caused
      cell loss in the ganglion cell layer and thinning of the inner plexiform and
      nuclear layer. Both ocular topical and intravenous administration of 2-CN-Ado
      caused a reduction of retinal ischaemia/reperfusion damage. A selective A2A
      receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine (CSC), but not a
      selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or
      a selective A2B receptor antagonist, alloxazine, reduced the protective effect of
      2-CN-Ado. While ocular topical administration of 2-CN-Ado caused a sustained
      reduction of intraocular pressure, intravenous administration of 2-CN-Ado showed
      a transient ocular hypotensive effect. CONCLUSIONS: These results suggest that 2
      CN-Ado attenuates retinal ischaemia/reperfusion damage, and at least some of this
      protective effect of 2-CN-Ado might be mediated via activation of the adenosine
      A2A receptor.

PMID- 16613922
TI  - Involvement of programmed death-ligand 2 (PD-L2) in the development of
      experimental allergic conjunctivitis in mice.
AB  - BACKGROUND/AIM: Involvement of programmed death-1 (PD-1) and its ligands has been
      demonstrated in experimental allergic airway disease. Here, the authors aimed to
      examine whether PD-1 and its ligands are involved in the development of
      experimental allergic conjunctivitis (EC) in mice. METHODS: EC was induced in
      Balb/c mice by active immunisation with short ragweed pollen (RW) in alum. 10
      days later (day 10), the mice were challenged with eye drops containing RW. 24
      hours after the challenge, conjunctivas, spleens, and sera were harvested for
      histological analysis, cytokine assays, and measurement of RW specific Ig levels.
      The actively immunised mice were treated with anti-PD-1, anti-PD-L1, anti-PD-L2
      antibodies (Abs), or normal rat immunoglobulin G (nrIgG) during either the
      induction (day 0, 2, 4, 6, and 8) or the effector (2 hours before RW challenge on
      day 10) phase. RESULTS: Ab treatment during the induction phase did not affect
      eosinophil infiltration although immune responses were modulated. In contrast,
      treatment with anti-PD-L2 Ab, but not anti-PD-1 or anti-PD-L1 Ab, during the
      effector phase significantly increased eosinophil infiltration into the
      conjunctiva without affecting systemic immune responses. CONCLUSIONS: Similar to
      allergic airway inflammation, PD-L2 is involved in the development of EC during
      the effector phase but not the induction phase.

PMID- 16613923
TI  - Location of glaucoma drainage devices relative to the optic nerve.
AB  - BACKGROUND: Limited data are available to guide optimal positioning of glaucoma
      drainage devices (GDD) in relation to the limbus and optic nerve. The authors aim
      to provide guidelines for appropriate and safe GDD implantation. METHOD: The
      optimal positioning of five different GDD were evaluated using necropsy eyes of
      varying axial lengths. The dependent variable that was measured was the maximum
      distance that a GDD could be placed posterior to the limbus while remaining 2 mm
      away from the optic nerve. RESULTS: The average maximum distance posterior to the
      limbus of the anterior plate edge ranged between 9.0-15.0 mm in the
      superotemporal quadrant for the GDD tested. The distances for superonasal,
      inferonasal, and inferotemporal quadrants ranged between 8.0-14.0 mm, 9.0-14.0
      mm, and 11.0-17.0 mm, respectively. The Molteno device could be placed most
      posteriorly while remaining 2 mm away from the nerve. The Ahmed FP7 and S2 were
      the least amenable to posterior placement before encroaching on the 2 mm limit.
      CONCLUSION: The maximum distance that a GDD can be placed posterior to the
      limbus, before encroachment around the optic nerve, varies between different
      devices and quadrants of placement. Taking a measurement of the exact distance of
      the plate from the limbus during GDD surgery is recommended.

PMID- 16613924
TI  - Verteporfin photodynamic therapy induced apoptosis in choroidal neovascular
      membranes.
AB  - AIM: To evaluate the impact of verteporfin photodynamic therapy (PDT) on the
      induction of apoptosis in choroidal neovascular membranes (CNV) secondary to age
      related macular degeneration. METHODS: Retrospective review of 22 surgically
      excised CNV. 12 of these patients had been treated with PDT 3-146 days
      previously. Apoptotic cells were detected with the TUNEL technique and compared
      to the expression of CD34 (endothelial cells, EC), CD105 (activated endothelial
      cells), Ki-67 (proliferation marker), and cytokeratin18 (retinal pigment
      epithelial cells, RPE). RESULTS: CNV excised 3 days after PDT were characterised
      both by collapsed and patent vessels. The EC displayed a statistical significant
      positive TUNEL reaction when compared to the remaining treated CNV (p < 0.001)
      and untreated CNV (P = 0.002). The proliferative activity was reduced. CNV
      excised 1-5 months after PDT displayed a patent vascularisation and high
      proliferative activity. All membranes either treated or untreated disclosed only
      sporadic TUNEL positive cells within the stroma and the RPE. CONCLUSIONS:
      Verteporfin PDT leads to selective and effective damage of EC within CNV. Both
      patent and occluded vessels were lined by apoptotic EC. This finding and the
      increased expression of proliferation marker at later time points suggest that
      revascularisation after PDT is caused by angiogenesis rather than recanalisation.

PMID- 16613925
TI  - Stage of presentation and visual outcome of patients screened for familial
      retinoblastoma: nationwide registration in the Netherlands.
AB  - BACKGROUND: In the Netherlands a comprehensive programme for screening just after
      birth for familial retinoblastoma is taking place. In this report the stage of
      the disease at the time of detection, by way of screening, and the long term
      visual outcome in these patients was evaluated. METHODS: A nationwide,
      retrospective study. From January 1992-July 2004, patients at risk for familial
      retinoblastoma were screened 1-2 weeks after birth, and investigated for
      laterality, Reese-Ellsworth classification/International Classification of
      Retinoblastoma, macular involvement, age of primary retinoblastoma, initial
      therapy, and visual outcome. RESULTS: 17 patients were diagnosed with familial
      retinoblastoma. 88.3% developed bilateral, 11.7% unilateral retinoblastoma. Of
      the 34 eyes, 56% were R-E group I, 16% were group II A-B, 16% were group III A-B,
      9% were group IV, 3% were group V. Using the International Classification of
      Retinoblastoma, 72% were group A, 19% were group B, 6% were group C, 3% were
      group E. The visual outcome revealed 73.5% of eyes with 20/20-20/40, 26.5% eyes
      with < or = 20/100-no light perception; 5.9% of eyes were enucleated, all other
      eyes were treated with local or conservative treatment methods. Of all eyes, 59%
      had extramacular retinoblastoma, 98% of patients had at least one eye with
      extramacular retinoblastoma. CONCLUSION: Most familial retinoblastoma patients
      present as a R-E group I or group A when screened within 2 weeks after birth.
      Nearly 90% of patients had a long term visual acuity of 20/20-20/40. Despite the
      common occurrence of macula involvement, bilateral macula involvement was
      infrequent, and since most eyes were salvaged, good vision was obtained in the
      majority of patients.

PMID- 16613926
TI  - Nitric oxide and liver microcirculation during autoregulation and haemorrhagic
      shock in rabbit model.
AB  - BACKGROUND: Direct evidence of nitric oxide (NO) involvement in the regulation of
      hepatic microcirculation is not yet available under physiological conditions nor
      in haemorrhagic shock. METHODS: A laser Doppler flowmetry was used to measure
      liver perfusion index and a specific NO-sensitive electrode was inserted into
      liver parenchyma of anaesthetized rabbits. Hepatic autoregulation during moderate
      hypovolaemia {mean arterial pressure at 50 mm Hg without liver perfusion
      alteration; blood withdrawal 17.7 (4.2) ml [mean (SD)]} or haemorrhagic shock
      [mean arterial pressure at 20 mm Hg associated with liver perfusion impairment
      and lactic acidosis; blood withdrawal 56.0 (6.8) ml] were investigated over 60
      min and were followed by a rapid infusion of the shed blood. Involvement of NO
      synthases was evaluated using a non-specific inhibitor, NAPNA (Nomega-nitro-L
      arginine P-nitro-anilide). RESULTS: In the autoregulation group, a decrease [30.0
      (4.0) mm Hg] of mean arterial pressure did not alter liver perfusion index,
      whereas the liver NO concentration increased and reached a plateau [125 (10)%;
      compared with baseline; P<0.05]. This NO concentration was reduced to zero by the
      administration of NO synthase inhibitor. Haemorrhagic shock led to a rapid
      decrease in liver perfusion index [60 (7)%; compared with baseline; P<0.05]
      before an immediate and continuous increase in NO concentration [250 (50)%;
      compared with baseline; P<0.05]. Infusion of NO inhibitor before haemorrhagic
      shock reduced the NO concentration to zero and hepatic perfusion by 60 (8)%
      (P<0.05) of the baseline. Mean arterial pressure increased simultaneously. In
      these animals, during haemorrhage, a continuous increase in NO concentration
      still occurred and liver perfusion slightly increased. In all groups but
      NAPNA+haemorrhagic shock, blood replacement induced recovery of baseline values.
      CONCLUSIONS: NO plays a physiological role in the liver microcirculation during
      autoregulation. Its production is enzyme-dependent. Conversely, haemorrhagic
      shock induces a rapid increase in hepatic NO that is at least partially enzyme
      independent.

PMID- 16613927
TI  - Emergence and recovery in children after desflurane and isoflurane anaesthesia:
      effect of anaesthetic duration.
AB  - BACKGROUND: We hypothesized that increasing duration of inhalation anaesthesia is
      associated with slower emergence and recovery in children, and that this effect
      would be less marked with desflurane in comparison with isoflurane. METHODS:
      Fifty-four infants and children assigned in groups according to age and expected
      length of operation were prospectively randomized to receive either isoflurane
      (I) or desflurane (D) for anaesthesia. After standard induction, the anaesthesia
      was maintained using an age-related 1.0 minimum alveolar concentration (MAC)
      equivalent for either agent in air and oxygen. Local analgesia was used as
      appropriate. End-tidal volatile agent concentration was recorded until
      extubation. Clinical evaluation of recovery was made by observers, blinded to
      group allocation. RESULTS: For patients <4 yr of age, the median (95% CI) times
      in minutes to first movement [5.27 (D), 9.22 (I)], eye opening [9.42(D), 13.3(I)]
      and extubation [7.18 (D), 12.5 (I)] were significantly shorter (P<0.05) for
      desflurane. In the group >4 yr of age, the median (95% CI) times in minutes to
      first movement [4.42 (D), 11.6 (I)], eye opening [8.55(D), 18.0(I)] and
      extubation [7.08 (D), 16.7 (I)] were significantly shorter (P<0.001) for
      desflurane. Times to leave recovery were not significantly different for the
      group <4 yr of age, but were significantly shorter for desflurane in the group >4
      yr of age (P<0.01). The isoflurane, but not desflurane, had a time-dependent
      effect on arousal. There were no significant differences in incidence of airway
      irritation or emergence delirium between the two agents. CONCLUSIONS: The rate of
      recovery in children after exposure to desflurane was faster than those patients
      receiving isoflurane; recovery from desflurane, but not isoflurane, was
      relatively unaffected by the duration of anaesthesia.

PMID- 16613928
TI  - Effects of intraoperative i.v. acetaminophen vs i.m. meperidine on post
      tonsillectomy pain in children.
AB  - BACKGROUND: Enteral acetaminophen, when used alone, is not very effective for
      postoperative analgesia because of delayed absorption and sub-therapeutic plasma
      concentrations. In contrast, i.v. acetaminophen is devoid of these shortcomings
      and could potentially provide adequate postoperative analgesia as a single agent.
      This randomized double-blind study compared the analgesic effects of i.v.
      acetaminophen and i.m. meperidine in paediatric patients undergoing
      tonsillectomy. METHODS: Eighty children undergoing tonsillectomy were randomized
      to receive either acetaminophen 15 mg kg(-1) i.v. (acetaminophen group) or
      meperidine 1 mg kg(-1) i.m. (meperidine group), intraoperatively. Anaesthesia was
      induced with either sevoflurane inhalation or propofol, and was maintained with
      sevoflurane. After operation, the objective pain scale (OPS), Ramsay sedation
      score and Aldrete score were recorded every 5 min, and nurses' satisfaction was
      determined on a 7-point scale (1-7). RESULTS: On admission to the recovery room,
      OPS scores were 3.1 (sem 0.3) for the acetaminophen group and 2.1 (sem 0.3) for
      the meperidine group (P=0.147); however, Ramsay sedation scores were 3 (sem 0.2)
      and 4 (sem 0.3) for the acetaminophen and meperidine groups, respectively
      (P<0.05). Patients in the meperidine group continued to be more sedated 5 min
      after arrival in recovery (P<0.05). Acetaminophen group patients achieved an
      Aldrete score of 10 min sooner than those in the meperidine group [median (IQR)
      time: 15 (0-20) min vs 25 (15-30) min, respectively, P=0.005]. Adjusted nurse
      satisfaction scores were similar in both groups [6.1 (sem 0.2) vs 5.7 (sem 0.2)
      min, P=0.311]. CONCLUSION: Compared with i.m. meperidine, i.v. acetaminophen
      provided adequate analgesia, less sedation and earlier readiness for recovery
      room discharge among paediatric patients undergoing tonsillectomy.

PMID- 16613929
TI  - Determination of interobserver variability for identifying inducible left
      ventricular wall motion abnormalities during dobutamine stress magnetic resonance
      imaging.
AB  - AIMS: To determine the interobserver variability for identifying inducible left
      ventricular (LV) wall motion abnormalities during high-dose dobutamine/atropine
      stress cardiovascular magnetic resonance (DSMR). METHODS AND RESULTS: Four
      readers from various institutions were supplied with the image data from 150
      consecutive DSMR examinations and asked to grade wall motion and image quality
      throughout graded doses of dobutamine infusion administered to achieve 85% of the
      maximum age-predicted heart rate. Inducible ischaemia was identified if more than
      one segment demonstrated a new or worsening LV wall motion abnormality, and
      significant stenosis was defined as > or =50% luminal diameter reduction by
      quantitative contrast coronary angiography. Seventy-seven patients (51%) had
      luminal narrowings > or =50%. Diagnostic performance (sensitivity, specificity,
      diagnostic accuracy) of all readers was 78.2, 87.0 and 82.5%. Disagreement
      between two readers occurred in every seventh examination. Agreement on the
      presence or absence of inducible wall motion abnormalities was moderate (mean
      kappa value 0.59, range 0.52-0.76). Diagnostic performance and disagreement were
      independent of the presence of luminal narrowings > or =50% or the number of
      diseased coronary vessels. Image quality was regarded excellent in 89.3% of
      standard views. CONCLUSION: In the setting of multiple observers from different
      institutions performing a diagnostic reading of DSMR examinations carried out at
      a single centre, the interobserver variability was low for identifying inducible
      LV wall motion abnormalities indicative of coronary arterial luminal narrowings >
      or =50%.

PMID- 16613930
TI  - Exercise and inflammation.

PMID- 16613931
TI  - What is the most useful and cost-effective strategy to screen for left
      ventricular systolic dysfunction in clinical practice?

PMID- 16613932
TI  - Radiofrequency ablation of arrhythmias guided by non-fluoroscopic catheter
      location: a prospective randomized trial.
AB  - AIMS: To compare the utility of non-fluoroscopic mapping systems (Carto and
      Ensite NavX) with that of conventional mapping in patients referred for catheter
      ablation of a wide variety of arrhythmias. METHODS AND RESULTS: Patients referred
      for catheter ablation (excluding atrial fibrillation, atypical atrial flutter,
      ventricular tachycardia in structural heart disease, and complete AV nodal
      ablation) were randomized equally to a procedure guided by Carto, Ensite NavX, or
      conventional mapping. A total of 145 patients were recruited (82 men, aged 49+/
      16, range 18-85). In 19 patients, no ablation was performed, and in the
      remaining, typical atrial flutter, atrioventricular nodal re-entrant tachycardia,
      and atrioventricular re-entrant tachycardias [including Wolff-Parkinson-White
      (WPW)] accounted for 93% of ablations. Overall procedure time, immediate and
      short-term success, complication rate, and freedom from symptoms at follow-up
      were identical for all groups. NavX led to the least X-ray exposure: Navx vs.
      conventional, median (range): 4 (0-50) vs. 13 (2-46) min (P<0.001); NavX vs.
      Carto, median (range): 4 (0-50) vs. 6 (1-55) min (P=0.008). Both Carto and NavX
      increased disposable costs by 50% when compared with conventional (P<0.001). For
      typical atrial flutter, Carto and NavX reduced screening times without increasing
      procedure cost. If ablation was not performed, NavX was twice as expensive as
      Carto or conventional. CONCLUSION: Ensite NavX and Carto procedures have similar
      effectiveness and safety to a conventional approach; however, they both reduce X
      ray exposure, with NavX producing a significantly greater effect than Carto.
      Although this benefit is achieved at a greater financial cost, there may be long
      term benefits to catheter laboratory staff.

PMID- 16613933
TI  - Usefulness of ECG-gated multi-detector computed tomography for the diagnosis of
      mechanical prosthetic valve dysfunction.

PMID- 16613934
TI  - Incidental finding of a ruptured thin-cap fibroatheroma by optical coherence
      tomography.

PMID- 16613935
TI  - Breast cancer in the family--children's perceptions of their mother's cancer and
      its initial treatment: qualitative study.
AB  - OBJECTIVES: To explore how children of mothers newly diagnosed with breast cancer
      perceive their mother's illness and its initial treatment; to contrast their
      accounts with the mothers' perceptions of their children's knowledge. DESIGN:
      Qualitative interview study with thematic analysis. SETTING: Home based
      interviews with mothers and children in Oxfordshire, England. PARTICIPANTS: 37
      mothers with early breast cancer and 31 of their children aged between 6 and 18
      years. RESULTS: Awareness of cancer as a life threatening illness existed even
      among most of the youngest children interviewed. Children described specific
      aspects of their mother's treatment as especially stressful (seeing her
      immediately postoperatively, chemotherapy, and hair loss). Children suspected
      that something was wrong even before they were told the diagnosis. Parents
      sometimes misunderstood their children's reactions and underestimated the
      emotional impact or did not recognise the children's need for more preparation
      and age appropriate information about the illness and its treatment. CONCLUSIONS:
      As part of their care, parents newly diagnosed with a life threatening illness
      need to be supported to think about how they will talk to their children. General
      practitioners and hospital specialists, as well as nurses, are well placed to be
      able to help with these concerns and if necessary to be involved in discussions
      with the children. The provision of appropriate information, including
      recommended websites, should be part of this care. More information specifically
      designed for young children is needed.

PMID- 16613936
TI  - Prevalence of deliberate self harm and attempted suicide within contemporary Goth
      youth subculture: longitudinal cohort study.
AB  - OBJECTIVE: To investigate whether deliberate self harm is associated with
      contemporary Goth youth subculture. DESIGN: Longitudinal cohort study. SETTING:
      School and community based study of young people living in the Central Clydeside
      Conurbation, Scotland. PARTICIPANTS: 1258 people aged 19, surveyed in 2002-4 and
      followed-up since age 11 (1994). MAIN OUTCOME MEASURES: Lifetime prevalence of
      self harm and attempted suicide and their association with Goth youth subculture,
      before and after adjusting for confounders. RESULTS: Identification as belonging
      to the Goth subculture was strongly associated with lifetime self harm and
      attempted suicide, with a prevalence of 53% and 47%, respectively among the most
      highly identified group, and evidence for a dose-response relation. Adjusting for
      potential confounders did not significantly attenuate this association. Analysis
      of other youth subcultures showed that this effect was primarily associated with
      Goth subculture. CONCLUSIONS: Identification as belonging to the Goth subculture
      was the best predictor of self harm and attempted suicide. Although based on
      small numbers, additional longitudinal analysis suggests both selection and
      modelling mechanisms are involved, selection mechanisms possibly being more
      likely.

PMID- 16613937
TI  - Medical academia is failing patients and clinicians.

PMID- 16613938
TI  - Brains and mobile phones.

PMID- 16613939
TI  - Strict glucose control in the critically ill.

PMID- 16613940
TI  - Regulating the collection and use of fetal stem cells.

PMID- 16613941
TI  - The care of older people.

PMID- 16613942
TI  - US lags in health care despite largest investment, survey shows.

PMID- 16613943
TI  - Massachusetts is to provide health care for 99% of population.

PMID- 16613944
TI  - Inquiry into adverse events in trial blames drug, not study design.

PMID- 16613945
TI  - UK launches panel to tackle research misconduct.

PMID- 16613946
TI  - Disease awareness campaigns turn healthy people into patients.

PMID- 16613947
TI  - Uganda sees a rise of 12% in TB cases.

PMID- 16613948
TI  - Nine drug company chiefs are charged with conspiracy to defraud NHS.

PMID- 16613949
TI  - EU warns four countries over tobacco advertising.

PMID- 16613951
TI  - Guidance does not require mandatory reporting of underage sex.

PMID- 16613952
TI  - Chance of bird flu mutating into virus transmissible between humans is "very
      low".

PMID- 16613953
TI  - Links between doctors across the world bring benefits.

PMID- 16613956
TI  - Agency is creating a pan-European drug database.

PMID- 16613959
TI  - Conference warns of epidemic of unsafe abortions in Africa.

PMID- 16613961
TI  - Metabolic syndrome and mortality.

PMID- 16613962
TI  - Nicorandil may be associated with gastrointestinal ulceration.

PMID- 16613963
TI  - Systemic lupus erythematosus.

PMID- 16613964
TI  - Understanding the NSAID related risk of vascular events.

PMID- 16613966
TI  - ABC of wound healing. Non-surgical and drug treatments.

PMID- 16613969
TI  - Seven years of feast, seven years of famine: boom to bust in the NHS?

PMID- 16613970
TI  - Can fetuses feel pain?

PMID- 16613971
TI  - Non-European doctors and change in UK policy: ten thousand international medical
      graduates may be affected.

PMID- 16613972
TI  - Bird flu: pandemic flu at the coal face.

PMID- 16613973
TI  - Bird flu: pandemic flu is not just about probability.

PMID- 16613974
TI  - Bird flu: pandemic flu preparation: an unheeded lesson from SARS.

PMID- 16613975
TI  - NHS financial crisis: signs of crisis or hope?

PMID- 16613976
TI  - Non-European doctors and change in UK policy: change is cruel and opportunistic.

PMID- 16613977
TI  - Non-European doctors and change in UK policy: what about highly skilled migrant
      doctors?

PMID- 16613979
TI  - Risks and benefits of omega 3 fats: a few thoughts on systematic review.

PMID- 16613980
TI  - Risks and benefits of omega 3 fats: health benefits of omega 3 fats are in doubt.

PMID- 16613981
TI  - New disease: motivational deficiency disorder: too much effort.

PMID- 16613982
TI  - New disease: motivational deficiency disorder: study ignores economic benefits.

PMID- 16613983
TI  - Entrenched misinformation about X and Y sperm.

PMID- 16613984
TI  - Something old, something new in wound dressings.

PMID- 16613985
TI  - Benefits from detecting dementia are dubious.

PMID- 16613986
TI  - From outdated to updated, keeping clinical guidelines valid.

PMID- 16613987
TI  - 1,25-Dihydroxyvitamin D3 regulates the expression of low-density lipoprotein
      receptor-related protein 5 via deoxyribonucleic acid sequence elements located
      downstream of the start site of transcription.
AB  - The skeleton is a direct target of vitamin D action, where the hormone modulates
      the proliferation of osteoblast precursors, their differentiation into mature
      osteoblasts, and their functional activity. Some of these effects of vitamin D
      are reminiscent of those orchestrated by the Wnt signaling pathway wherein
      stimulation of the membrane receptor Frizzled and its coreceptor LRP5 leads to
      activation of beta-catenin and subsequent transcription-mediated changes in
      osteoblast biology. Indeed, LRP5 is now known to play a particularly important
      role in bone formation such that the loss of this component results in a
      reduction in osteoblast number, a delay in mineralization, and a reduction in
      peak bone mineral density. Interestingly, we discovered during the course of a
      vitamin D receptor (VDR) chromatin immunoprecipitation/DNA microarray analysis
      that 1,25-(OH)2D3 could induce binding of the VDR to sites within the Lrp5 gene
      locus. VDR and retinoid X receptor binding was evident both in primary
      osteoblasts as well as in osteoblasts of cell line origin. Importantly, this
      interaction between 1,25-(OH)2D3-activated VDR and the Lrp5 gene led to both a
      modification in chromatin structure within the Lrp5 locus and the induction of
      Lrp5 mRNA transcripts in vivo as well as in vitro. One of these sites within the
      Lrp5 locus was discovered to confer vitamin D response to a heterologous promoter
      when introduced into osteoblastic cells, permitting both the identification and
      characterization of the vitamin D response element located within. Interestingly,
      additional studies revealed that whereas the regulatory region in the mouse Lrp5
      gene was highly conserved in the human genome, the vitamin D response element was
      not. Our studies show that 1,25-(OH)2D3 can enhance the expression of a critical
      component of the Wnt signaling pathway that is known to impact osteogenesis.

PMID- 16613988
TI  - Functional inactivation of the transcription factor Pax8 through oligomerization
      chain reaction.
AB  - Among the approaches used to provide a functional inactivation of a target
      protein, we have chosen the recently described oligomerization chain reaction
      (OCR) strategy to functionally inactivate the transcription factor Pax8, a member
      of the Pax gene family expressed in thyroid cells. The OCR strategy is based on
      the fusion of the self-associating coiled-coil (CC) domain of the nuclear factor
      promyelocytic leukemia (PML) to target proteins that are able to self-associate
      naturally or that form heterocomplexes. In the thyroid tissue, the transcription
      factor Pax8 is involved in the morphogenesis of the gland and in the
      transcriptional regulation of thyroid-expressed genes. We have recently
      demonstrated that in thyroid cells Pax8 interacts biochemically and functionally
      with the transcription factor TTF-1 (thyroid transcription factor 1), and that
      such interaction leads to the synergistic activation of thyroglobulin (Tg) gene
      expression. Fusion of the CC domain to Pax8 leads to the formation of aberrant,
      nonfunctional high-molecular mass complexes to which TTF-1 is also recruited. The
      CC-Pax8 chimera inhibits the transcriptional activity of Pax8 and of TTF-1 on
      both synthetic and physiological promoters and prevents the synergistic
      activation of the Tg promoter mediated by these two transcription factors.
      Furthermore, the expression of the CC-Pax8 chimera in differentiated thyroid
      cells leads to the down-regulation of the endogenous expression of several
      differentiation markers such as Tg, sodium/iodide symporter, Foxe1, TTF-1, and
      thyroid oxidase 2. These results demonstrate that the OCR is a useful tool to
      functionally inactivate a transcription factor. Moreover, by this approach, we
      identified Foxe1, TTF-1, and thyroid oxidase 2 as new direct targets of Pax8 or
      TTF-1.

PMID- 16613989
TI  - Down-regulation of the tumor suppressor gene retinoic acid receptor beta2 through
      the phosphoinositide 3-kinase/Akt signaling pathway.
AB  - The retinoic acid receptor beta2 (RARbeta2) is a potent, retinoid-inducible tumor
      suppressor gene, which is a critical molecular relay for retinoid actions in
      cells. Its down-regulation, or loss of expression, leads to resistance of cancer
      cells to retinoid treatment. Up to now, no primary mechanism underlying the
      repression of the RARbeta2 gene expression, hence affecting cellular retinoid
      sensitivity, has been identified. Here, we demonstrate that the phosphoinositide
      3-kinase/Akt signaling pathway affects cellular retinoid sensitivity, by
      regulating corepressor recruitment to the RARbeta2 promoter. Through direct
      phosphorylation of the corepressor silencing mediator for retinoic and thyroid
      hormone receptors (SMRT), Akt stabilized RAR/SMRT interaction, leading to an
      increased tethering of SMRT to the RARbeta2 promoter, decreased histone
      acetylation, down-regulation of the RARbeta2 expression, and impaired cellular
      differentiation in response to retinoid. The phosphoinositide 3-kinase/Akt
      signaling pathway, an important modulator of cellular survival, has thus a direct
      impact on cellular retinoid sensitivity, and its deregulation may be the
      triggering event in retinoid resistance of cancer cells.

PMID- 16613990
TI  - The LIM-homeodomain proteins Isl-1 and Lhx3 act with steroidogenic factor 1 to
      enhance gonadotrope-specific activity of the gonadotropin-releasing hormone
      receptor gene promoter.
AB  - The GnRH receptor (GnRH-R) plays a central role in mammalian reproductive
      function throughout adulthood. It also appears as an early marker gene of the
      presumptive gonadotrope lineage in developing pituitary. Here, using transient
      transfections combined with DNA/protein interaction assays, we have delineated
      cis-acting elements within the rat GnRH-R gene promoter that represent targets
      for the LIM-homeodomain (LIM-HD) proteins, Isl-1 and Lhx3. These factors,
      critical in early pituitary development, are thus also crucial for gonadotrope
      specific expression of the GnRH-R gene. In heterologous cells, the expression of
      Isl-1 and Lhx3, together with steroidogenic factor 1 (SF-1), culminates in the
      activation of both the rat as well as human GnRH-R promoter, suggesting that this
      combination is evolutionarily conserved among mammals. The specificity of these
      LIM-HD factors is attested by the inefficiency of related proteins, including
      Lhx5 and Lhx9, to activate the GnRH-R gene promoter, as well as by the repressive
      capacity of a dominant-negative derivative of Lhx3. Accordingly, targeted
      deletion of the LIM response element decreases promoter activity. In addition,
      experiments with Gal4-SF-1 fusion proteins suggest that LIM-HD protein activity
      in gonadotrope cells is dependent upon SF-1 binding. Finally, using a transgenic
      model that allows monitoring of in vivo promoter activity, we show that the
      overlapping expression of Isl-1 and Lhx3 in the developing pituitary correlates
      with promoter activity. Collectively, these data suggest the occurrence of a
      specific LIM-HD pituitary code and designate the GnRH-R gene as the first
      identified transcriptional target of Isl-1 in the anterior pituitary.

PMID- 16613991
TI  - Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in
      vertebrates.
AB  - Dietary and xenobiotic compounds can disrupt endocrine signaling, particularly of
      steroid receptors and sexual differentiation. Evidence is also mounting that
      implicates environmental agents in the growing epidemic of obesity. Despite a
      long-standing interest in such compounds, their identity has remained elusive.
      Here we show that the persistent and ubiquitous environmental contaminant,
      tributyltin chloride (TBT), induces the differentiation of adipocytes in vitro
      and increases adipose mass in vivo. TBT is a dual, nanomolar affinity ligand for
      both the retinoid X receptor (RXR) and the peroxisome proliferator-activated
      receptor gamma (PPARgamma). TBT promotes adipogenesis in the murine 3T3-L1 cell
      model and perturbs key regulators of adipogenesis and lipogenic pathways in vivo.
      Moreover, in utero exposure to TBT leads to strikingly elevated lipid
      accumulation in adipose depots, liver, and testis of neonate mice and results in
      increased epididymal adipose mass in adults. In the amphibian Xenopus laevis,
      ectopic adipocytes form in and around gonadal tissues after organotin, RXR, or
      PPARgamma ligand exposure. TBT represents, to our knowledge, the first example of
      an environmental endocrine disrupter that promotes adipogenesis through RXR and
      PPARgamma activation. Developmental or chronic lifetime exposure to organotins
      may therefore act as a chemical stressor for obesity and related disorders.

PMID- 16613992
TI  - Autocrine/paracrine regulation of breast cancer cell proliferation by growth
      hormone releasing hormone via Ras, Raf, and mitogen-activated protein kinase.
AB  - Although GHRH has previously been shown to regulate proliferation of breast
      cancer cells and prevent apoptosis, the intracellular pathways mediating this
      effect have not been clarified. Exogenous GHRH stimulated a dose-dependent
      proliferative response within 24 h in MDA-231, as well as in T47D cells and in
      MCF-7 cells transfected with the GHRH receptor. The proliferation of MDA-MB-231
      (MDA-231) cells was associated with an increase in tritiated thymidine uptake. In
      addition, phosphorylation of MAPK was rapidly stimulated by GHRH. The
      phosphorylation of MAPK by GHRH was prevented by transfection of the cells with
      dominant-negative Ras or Raf or by pretreatment of cells with Raf kinase 1
      inhibitor. The inhibition of Ras and Raf, as well as the inhibition of MAPK
      phosphorylation by PD98059, also prevented GHRH-induced cell proliferation.
      Finally, pretreatment of cells with the somatostatin analog, BIM23014, also
      prevented GHRH-induced MAPK phosphorylation and cell proliferation. These results
      indicate that GHRH stimulates dose-dependent cell proliferation of MDA-231 breast
      cancer cells through a pathway that requires Ras, Raf, and MAPK phosphorylation.
      The results also provide support for a possible autocrine/paracrine antagonism
      between GHRH and somatostatin in the regulation of MDA-231 cell population
      maintenance. Taken together, the studies provide further insight into the
      possible role of GHRH as a growth factor in breast cancer.

PMID- 16613993
TI  - Psychiatric co-morbidities in patients attending specialist obesity services in
      the UK.
AB  - BACKGROUND: The prevalence of obesity is rising, but little is known about its
      psychosocial correlates. AIM: To assess psychological co-morbidities and
      impairment of quality of life in obese individuals seeking treatment at two
      specialist centres in the UK. DESIGN: Retrospective analysis of anthropometric
      and questionnaire data collected at initial clinic visit. METHODS: Patients
      attending for a first visit between April 2004 and March 2005 completed
      questionnaires that included scales for measurement of anxiety and depression
      (Hospital Anxiety and Depression Scale), eating disorder-behaviour (Eating
      Disorder Inventory 2), assessment of body image (Body Image Assessment for
      Obesity) and quality of life (Impact of Weight on Quality of Life-Lite). We
      examined the relationships between variables measured on these scales and
      anthropometric data. RESULTS: Of 253 questionnaires evaluated, there were
      elevated scores for depression in 48%, and elevated scores for anxiety in 56%.
      Twenty-two percent demonstrated scores suggestive of a personality trait that
      overlaps with an eating disorder; an additional 11.5% had an elevated score for
      bulimia. About a third of individuals had significant impaired quality of life in
      the areas of examined. DISCUSSION: Psychological co-morbidities are common in
      obese individuals attending specialist weight-management clinics, and may merit
      consideration at (or before) commencement of a weight loss programme.

PMID- 16613994
TI  - Factor V Leiden, pregnancy complications and adverse outcomes: the Hordaland
      Homocysteine Study.
AB  - BACKGROUND: The factor V Leiden (FVL) mutation is the most common cause of
      inherited thrombophilia in Caucasian populations, and women with this variant
      allele are at increased risk for pregnancy complications. AIM: To examine whether
      the FVL allele is associated with pregnancy complications and adverse outcomes in
      a population-based study, and to identify potential factors that interact with
      the FVL genotype. DESIGN: Retrospective cohort study in a geographically-defined
      area. METHODS: Polymorphisms of factor V 1691G-->A, methylenetetrahydrofolate
      reductase (MTHFR) 677C --> T and 1298A --> C and plasma levels of total
      homocysteine, folate and vitamin B(12) were determined in blood samples collected
      in 1992-1993 from 5874 women aged 40-42 years, and linked with 14 474 pregnancies
      in the same women, recorded in the Medical Birth Registry of Norway, 1967-1996.
      RESULTS: The allelic frequency of FVL was 3.7% (6.9% heterozygotes, 0.3%
      homozygotes). Maternal FVL mutation was associated with significantly higher
      risks of pre-eclampsia (OR 1.63, 95%CI 1.15-2.30), pre-eclampsia at <37 weeks (OR
      2.76, 1.34-5.70), low birth weight (OR 1.34, 95%CI 1.03-1.74) and stillbirth (OR
      2.20, 95%CI 1.45-3.36). The presence of a variant allele for the 677C --> T MTHFR
      polymorphism strengthened the association between FVL and stillbirth (OR 3.34,
      95%CI 1.95-5.73) (p(interaction) = 0.034). DISCUSSION: FVL mutation is a
      significant risk factor for pregnancy complications and adverse outcomes, and
      MTHFR 677CT/TT genotype can further enhance the risk of stillbirth.

PMID- 16613995
TI  - Human P2X7 pore function predicts allele linkage disequilibrium.
AB  - BACKGROUND: Innate immune response amplification is achieved by leukocyte
      expression of the purinergic nucleotide receptor P2X7, an extracellular
      nucleotide-gated pore. Previously, low P2X7 pore activity in whole blood was
      associated with loss-of-function genotypes in correlation with a decreased ratio
      of lipopolysaccharide-stimulated tumor necrosis factor-alpha to interleukin-10,
      of relevance to a variety of infectious and inflammatory disorders. We
      hypothesized that evaluation of participants with discordance between the P2X7
      genotype and pore status would disclose additional alleles, linkage
      disequilibrium, and novel functional correlates of genotype to phenotype.
      METHODS: Comparison of whole-blood pore results with restriction fragment length
      polymorphism data for known loss-of-function genotypes from 200 healthy
      participants optimized the diagnostic threshold for low pore activity by ROC
      curve analysis. We identified novel alleles and inferred haplotypes by sequencing
      outlier genomic templates and by linkage analysis. RESULTS: With a refined
      threshold of low activity, a normal pore result had only a 2% probability of
      association with known loss-of-function variants. By contrast, the positive
      predictive value of low pore activity was 59% for identifying known alleles. DNA
      samples from this discordant group contained 28 P2X7 sequence variations. Linkage
      analysis demonstrated that A1513C, T1729A, and G946A are inherited independently
      from one another, although these loss-of-function variants are in disequilibrium
      with other alleles. When we segregated pore activity data according to genotypes,
      nonsynonymous sequence variations (G474A and A1405G) appeared to exhibit
      modulatory effects on P2X7 pore activity. CONCLUSIONS: Direct analysis of pore
      activity demonstrates functional interactions between P2X7 alleles. The
      performance characteristics of the whole-blood pore assay enables correlation of
      genomic variation with concomitant investigation of functional performance in
      clinical studies.

PMID- 16613996
TI  - Feasibility of standardization of serum C-peptide immunoassays with isotope
      dilution liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Serum C-peptide concentrations reflect pancreatic function in
      different clinical and diagnostic settings; however, the utility of C-peptide
      testing is limited by the lack of standardized commercial immunoassays.
      Standardization can best be done by split-sample comparison with a hierarchically
      higher reference measurement procedure with a set of native sera. For serum
      peptides, isotope-dilution liquid chromatography-mass spectrometry (ID-LC/MS) is
      recommended as a reference measurement procedure. METHODS: We evaluated the
      analytical performance characteristics of an ID-LC/tandem MS procedure for
      measurement of serum C-peptide after a 2-step solid-phase extraction. To
      investigate the feasibility of this procedure for use in standardization, we also
      performed a method comparison with 3 representative commercial assays. RESULTS:
      The ID-LC/tandem MS procedure showed maximum within-run, between-run, and total
      CVs on dedicated sera (C-peptide concentrations, 1.6 and 4.0 mug/L) of 2.1%,
      2.5%, and 2.9%, respectively; an accuracy of 94.6%-104.1%; a minimum trueness of
      98.1% (95% confidence interval, 96.2%-100.0%), and limits of quantification and
      detection of 0.15 and 0.03 mug/L, respectively. Deming linear regression analysis
      of the method-comparison data showed that the immunoassays correlated well with
      ID-MS and were specific, but lacked intercomparability and trueness. We propose
      that the deficiencies can be resolved by recalibration on the basis of the method
      comparison. CONCLUSIONS: The ID-LC/tandem MS procedure is suitable for specific
      and accurate measurement of basal and stimulated serum concentrations of
      proinsulin C-peptide fragment 33-63 and is suitable for use in standardization of
      C-peptide immunoassays.

PMID- 16613997
TI  - Early prediction of sepsis-induced disseminated intravascular coagulation with
      interleukin-10, interleukin-6, and RANTES in preterm infants.
AB  - BACKGROUND: The progression to disseminated intravascular coagulation (DIC) in
      infected very low birth weight (VLBW; <1500 g) infants is difficult to predict
      with precision at the onset of sepsis. We investigated the immunologic profiles
      of preterm infants with sepsis, using chemokine and cytokine measurements to
      predict the development of sepsis-induced DIC at the onset of infection. METHODS:
      We measured a panel of chemokines and cytokines at 0 and 24 h after clinical
      presentation in VLBW infants with suspected infection requiring full sepsis
      screening. The chemokines measured were interleukin (IL)-8, interferon-gamma
      inducible protein-10 (IP-10), monokine induced by interferon-gamma, monocyte
      chemoattractant protein-1, and regulated upon activation normal T-cell expressed
      and secreted (RANTES), and the cytokines were IL-6, IL-10, and tumor necrosis
      factor-alpha. RESULTS: Of 195 episodes of suspected clinical sepsis investigated,
      62 were culture-confirmed septicemia or necrotizing enterocolitis (28 of these
      infants developed DIC), 22 were culture-negative clinical infections, and 111
      involved noninfected episodes. All studied inflammatory mediators except RANTES
      showed significantly greater up-regulation in culture-positive infected infants
      than in noninfected infants at 0 and 24 h, whereas RANTES showed significant down
      regulation. The model that used plasma IL-10 (>208 ng/L), IL-6 (>168 ng/L), and
      RANTES (<3110 ng/L) at 0 h had sensitivity, specificity, and positive and
      negative predictive values of 100%, 97%, 85%, and 100%, respectively, for
      identifying infected patients who subsequently developed DIC. CONCLUSIONS: IL-10,
      IL-6, and RANTES measured at clinical presentation sensitively and accurately
      predicted the development of DIC in severely infected infants. This information
      could be vital for early and effective treatment of neonatal sepsis.

PMID- 16613998
TI  - Effect of vitamin B12 treatment on haptocorrin.
AB  - BACKGROUND: Haptocorrin (HC) carries the major part of circulating cobalamin, but
      whether HC is altered on treatment with vitamin B12 remains unknown. METHODS: Our
      study included 3 populations: a population of vegan men (n = 174; vegan
      population), of whom 63 were treated daily with 5 mg of oral vitamin B12 for 3
      months; a group of patients with a previous methylmalonic acid (MMA)
      concentration >0.4 micromol/L (n = 140; population with suspected deficiency), of
      which 69 were treated with weekly vitamin B12 injections (1 mg) for 4 weeks; and
      a subgroup of participants in a vitamin B intervention study (n = 88;
      nondeficient population), of whom 45 were treated daily with 0.4 mg of oral
      vitamin B12 for 3 months. Total HC and holoHC were measured by ELISA. Cobalamin
      was measured by an intrinsic factor (IF)-based assay. Samples were collected at
      baseline and 3 months after start of treatment. RESULTS: Compared with baseline
      results for the 3 study populations, total HC and holoHC increased 30 pmol/L for
      every 100 pmol/L increase in cobalamin. After treatment with vitamin B12, holoHC
      (P <0.0001) and total HC (P <0.0001) increased significantly in the vegan
      population. Only holoHC increased in the population with suspected deficiency (P
      <0.0001), whereas no alteration was observed in the nondeficient population.
      CONCLUSIONS: The HC concentration is decreased in severely cobalamin-deficient
      individuals and increases on treatment. The concentration of cobalamin also
      relates significantly to the HC concentration in nondeficient individuals.

PMID- 16613999
TI  - Comprehensive detection of disorders of purine and pyrimidine metabolism by HPLC
      with electrospray ionization tandem mass spectrometry.
AB  - BACKGROUND: Clinical presentation and disease severity in disorders of purine and
      pyrimidine metabolism vary considerably. We present a method that allows
      comprehensive, sensitive, and specific diagnosis of the entire spectrum of
      abnormalities in purine and pyrimidine metabolism in 1 analytical run. METHODS:
      We used reversed-phase HPLC electrospray ionization tandem mass spectrometry to
      investigate 24 metabolites of purine and pyrimidine metabolism in urine samples
      from healthy persons and from patients with confirmed diagnoses of inherited
      metabolic disorders. Urine samples were filtered and diluted to a creatinine
      concentration of 0.5 mmol/L. Stable-isotope-labeled internal standards were used
      for quantification. The metabolites were analyzed by multiple-reaction monitoring
      in positive and negative ionization modes. RESULTS: Total time of analysis was 20
      min. Recovery (n = 8) of a compound after addition of a known concentration was
      85%-133%. The mean intraday variation (n = 10) was 12%. The interday variation (n
      = 7) was < or =17%. Age-related reference intervals were established for each
      compound. Analysis of patient urine samples revealed major differences in tandem
      mass spectrometry profiles compared with those of control samples. Twelve
      deficiencies were reliably detected: hypoxanthine guanine phosphoribosyl
      transferase, xanthine dehydrogenase, purine nucleoside phosphorylase,
      adenylosuccinate lyase, uridine monophosphate synthase, adenosine deaminase,
      adenine phosphoribosyl transferase, molybdenum cofactor, thymidine phosphorylase,
      dihydropyrimidine dehydrogenase, dihydropyrimidinase, and beta-ureidopropionase.
      CONCLUSION: This method enables reliable detection of 13 defects in purine and
      pyrimidine metabolism in a single analytical run.

PMID- 16614000
TI  - Detection of a soluble form of BACE-1 in human cerebrospinal fluid by a sensitive
      activity assay.
AB  - BACKGROUND: Formation of deposits of the insoluble amyloid beta-peptide is
      believed to be causally related with neurodegeneration in Alzheimer disease (AD).
      The beta-peptide originates from a larger amyloid precursor protein (APP) by the
      action of proteolytic enzymes. The first proteolytic event leading to amyloid
      formation is the cleavage of APP by the membrane-bound aspartyl protease BACE-1,
      also known as memapsin-2. Inhibition of BACE-1 is thought to be a therapeutic
      approach to AD. Measuring BACE-1 activity in biological samples would be useful
      to elucidate the mechanism of AD and for development of AD drugs. METHODS: We
      developed a sensitive and specific activity assay for BACE-1. The assay is based
      on a genetically engineered proenzyme that is specifically activated by BACE-1.
      The resulting active enzyme is measured with a chromogenic substrate. The use of
      2 coupled reactions produces a detection limit as low as 0.4 pmol/L. RESULTS: The
      assay detected BACE-1 activity in extracts of human brain tissue as well as,
      unexpectedly, in human cerebrospinal fluid (CSF). Gel electrophoresis and Western
      blotting identified the BACE-1 present in CSF as a truncated soluble form of the
      originally membrane-bound BACE-1. CONCLUSION: Detection of the soluble form of
      BACE-1 in CSF, a relatively easily accessible biological fluid, may be useful for
      monitoring the effects of drug candidates in vivo and may have diagnostic or
      prognostic applications.

PMID- 16614001
TI  - Point: developing a curriculum in clinical pathology.

PMID- 16614002
TI  - Increased pregnancy-associated plasma protein-A as a marker for peripheral
      atherosclerosis: results from the Linz Peripheral Arterial Disease Study.
AB  - BACKGROUND: The aim of the present investigation was to test the hypothesis that
      pregnancy-associated plasma protein-A (PAPP-A), a zinc-binding metalloproteinase
      implicated in acute coronary syndrome, is associated with atherosclerotic
      peripheral arterial disease (PAD). METHODS: The study comprised 433 patients with
      symptomatic atherosclerotic PAD (i.e., chronic limb ischemia) and 433 controls
      matched to the patients with PAD in a 1:1 design by sex, age (+/-2 years), and
      diabetes mellitus status. Serum PAPP-A concentrations were measured with an
      enzymatically amplified 2-step sandwich-type immunoassay. RESULTS: The entire
      study sample included 612 male and 254 female patients with a median age of 68
      years. The median PAPP-A value was higher in the patients with PAD than in the
      referents (0.81 vs 0.64 mU/L; P <0.001). After we adjusted for several possible
      confounding variables with multivariable logistic regression, odds ratios for PAD
      were 1.59 (95% confidence interval, 1.00-2.52; P = 0.049), 2.28 (1.45-3.61; P
      <0.001), and 2.86 (1.78-4.59; P <0.001) in the 2nd, 3rd, and 4th quartiles of
      serum PAPP-A concentrations compared with the first quartile. In the present
      study, PAPP-A added to the predictive value of other markers commonly in use.
      CONCLUSIONS: PAPP-A was associated with atherosclerotic PAD in the elderly sample
      studied. Because atherosclerotic PAD is considered an indicator of systemic
      atherosclerotic disease in elderly patients, the present results indicate that
      circulating PAPP-A may be a marker for systemic atherosclerotic disease.

PMID- 16614003
TI  - Parathyroid hormone monitoring during total parathyroidectomy for renal
      hyperparathyroidism: pilot study of the impact of renal function and assay
      specificity.
AB  - BACKGROUND: Commonly used assays for intact parathyroid hormone (iPTH) detect not
      only the biologically active 84-amino acid hormone [PTH1-84], but cross-react
      with an N-terminal-truncated fragment. Because iPTH assays often fail to predict
      success of parathyroidectomy in patients with renal hyperparathyroidism (rHPT),
      we compared results of a 3rd-generation PTH1-84 assay (Bio-iPTH; Nichols
      Institute Diagnostics) with two 2nd-generation iPTH assays (from Nichols and
      Roche Diagnostics) by evaluating the PTH clearance kinetics during surgical
      treatment. METHODS: We collected blood samples in short time intervals from 35
      consecutive surgical patients with rHPT. Three patients had to be excluded from
      further calculations; the remainder were grouped according to kidney function and
      postoperative outcome. All samples were analyzed with the 3 automated PTH assays,
      which have different specificities. RESULTS: Twenty minutes after removal of the
      last gland, the PTH1-84 values decreased to within the reference intervals in all
      patients with total and subtotal resection; however, iPTH concentrations
      normalized in only one half of these patients. In patients with poor renal
      function, the half-life of PTH1-84 was shorter than the half-lives obtained with
      the iPTH assays. CONCLUSIONS: The accuracy of PTH monitoring during surgery for
      rHPT depends on renal function and assay specificity. All assays tested showed
      similar effectiveness in detecting missed glands, but the assay for PTH1-84 gave
      more reliable results than the iPTH assays, which overestimated the concentration
      of PTH and hampered the intrasurgical diagnosis of resection sufficiency.

PMID- 16614004
TI  - The role of the sca-1+/CD31- cardiac progenitor cell population in postinfarction
      left ventricular remodeling.
AB  - Cardiac stem cell-like populations exist in adult hearts, and their roles in
      cardiac repair remain to be defined. Sca-1 is an important surface marker for
      cardiac and other somatic stem cells. We hypothesized that heart-derived Sca
      1(+)/CD31(-) cells may play a role in myocardial infarction-induced cardiac
      repair/remodeling. Mouse heart-derived Sca-1(+)/CD31(-) cells cultured in vitro
      could be induced to express both endothelial cell and cardiomyocyte markers.
      Immunofluorescence staining and fluorescence-activated cell sorting analysis
      indicated that endogenous Sca-1(+)/CD31(-) cells were significantly increased in
      the mouse heart 7 days after myocardial infarction (MI). Western blotting
      confirmed elevated Sca-1 protein expression in myocardium 7 days after MI.
      Transplantation of Sca-1(+)/CD31(-) cells into the acutely infarcted mouse heart
      attenuated the functional decline and adverse structural remodeling initiated by
      MI as evidenced by an increased left ventricular (LV) ejection fraction, a
      decreased LV end-diastolic dimension, a decreased LV end-systolic dimension, a
      significant increase of myocardial neovascularization, and modest cardiomyocyte
      regeneration. Attenuation of LV remodeling was accompanied by remarkably improved
      myocardial bioenergetic characteristics. The beneficial effects of cell
      transplantation appear to primarily depend on paracrine effects of the
      transplanted cells on new vessel formation and native cardiomyocyte function. Sca
      1(+)/CD31(-) cells may hold therapeutic possibilities with regard to the
      treatment of ischemic heart disease.

PMID- 16614005
TI  - Notch signaling is inactive but inducible in human embryonic stem cells.
AB  - The NOTCH signaling pathway performs a wide range of critical functions in a
      number of different cell types during development and differentiation. The role
      of NOTCH signals in human embryonic stem cells (hESCs) has not been tested. We
      measured the activity of canonical NOTCH signaling in undifferentiated embryonic
      stem (ES) cells and tested the requirement for NOTCH activity in hESC self
      renewal or differentiation by growing hESCs in the presence of gamma-secretase
      inhibitors. Our results suggest that NOTCH signaling is not required for the
      propagation of undifferentiated human ES cells but instead is required for the
      maintenance of the differentiating cell types that accumulate in human ES cell
      cultures. Our studies suggest that NOTCH signaling is not required in human
      embryonic differentiation until the formation of extraembryonic, germ layer, or
      tissue-specific stem cells and progenitors.

PMID- 16614006
TI  - Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine
      kinase inhibitor imatinib does not impair engraftment of human CD133+ cells into
      NOD/SCIDbeta2mNull mice.
AB  - There is potential interest for combining allogeneic hematopoietic cell
      transplantation (HCT), and particularly allogeneic HCT with a nonmyeloablative
      regimen, to the tyrosine kinase inhibitor imatinib (Glivec; Novartis, Basel,
      Switzerland, http://www.novartis.com) in order to maximize anti-leukemic activity
      against Philadelphia chromosome-positive leukemias. However, because imatinib
      inhibits c-kit, the stem cell factor receptor, it could interfere with bone
      marrow engraftment. In this study, we examined the impact of imatinib on normal
      progenitor cell function. Imatinib decreased the colony-forming capacity of
      mobilized peripheral blood human CD133(+) cells but not that of long-term culture
      initiating cells. Imatinib also decreased the proliferation of cytokine
      stimulated CD133(+) cells but did not induce apoptosis of these cells. Expression
      of very late antigen (VLA)-4, VLA-5, and CXCR4 of CD133(+) cells was not modified
      by imatinib, but imatinib decreased the ability of CD133(+) cells to migrate.
      Finally, imatinib did not decrease engraftment of CD133(+) cells into irradiated
      nonobese diabetic/severe combined immunodeficient/beta2m(null) mice conditioned
      with 3 or 1 Gy total body irradiation. In summary, our results suggest that,
      despite inhibition of hematopoietic progenitor cell growth in vitro, imatinib
      does not interfere with hematopoietic stem cell engraftment.

PMID- 16614007
TI  - Anti-ganglioside complex antibodies in Miller Fisher syndrome.
AB  - BACKGROUND: Some ganglioside complexes (GSCs) are target antigens for serum
      antibodies in patients with Guillain-Barre syndrome (GBS). Anti-GSC antibodies
      may be associated with particular clinical features of GBS. OBJECTIVE: To
      investigate antibodies to GSCs in the sera of patients with Miller Fisher
      syndrome (MFS) characterised by elevation of the IgG anti-GQ1b antibody. RESULTS:
      In all, 7 of 12 (58%) consecutive patients with MFS were found to have IgG
      antibodies to GSCs containing GQ1b, of whom 5 had IgG antibodies to GQ1b-GM1
      complex (GQ1b/GM1) and 2 had antibodies to GQ1b/GD1a; 4 of 5 patients without
      sensory symptoms had anti-GQ1b/GM1 antibodies. CONCLUSIONS: At least three
      different specificities in MFS-associated antibodies, GQ1b-specific, anti
      GQ1b/GM1-positive and anti-GQ1b/GD1a-positive, were observed. In patients with
      MFS not only GQ1b itself but also clustered epitopes of GSCs, including GQ1b, may
      be considered to be prime target antigens for serum antibodies. A tendency to
      escape sensory disturbances is shown by anti-GQ1b/GM1-positive MFS.

PMID- 16614008
TI  - A pilot randomised controlled trial of a home-based exercise programme aimed at
      improving endurance and function in adults with neuromuscular disorders.
AB  - AIM: To investigate the feasibility and effect of a home-based exercise programme
      on walking endurance, muscle strength, fatigue and function in people with
      neuromuscular disorders (NMDs). METHODS: 20 adults with NMDs recruited to a
      control (n = 11) or exercise (n = 9) group were assessed by blinded assessors at
      baseline and at week 8. Walking and strengthening exercises were given to the
      exercise group in an 8-week home exercise programme. A 2-min walk distance was
      the main outcome measurement; isometric muscle strength, fatigue and function
      were secondary measurements. RESULTS: 2-min walk distances were not found to
      change in either group (p>0.05; control: mean 14.50 (SD 22.06) m; exercise: mean
      2.88 (SD 20.08) m), and no difference was observed in the change scores between
      groups (p>0.05). Leg muscle strength increased in the exercise group (p<0.05) but
      not in the control group (p>0.05). Significance was reached between the groups
      with respect to the difference in change in muscle strength scores in the right
      quadriceps (p<0.05; control: mean -2.82 (SD 4.87) kg; exercise: mean -7.08 (SD
      2.82) kg). No change was observed in fatigue or function scores (p<0.05).
      CONCLUSIONS: A home-based approach aimed at improving endurance in adults with
      NMDs is feasible and further investigation on a larger sample is warranted.

PMID- 16614009
TI  - Fulminant Devic disease successfully treated by lymphocytapheresis.

PMID- 16614010
TI  - Influence of APOE polymorphism on cognitive and behavioural outcome in moderate
      and severe traumatic brain injury.
AB  - AIM: To analyse the influence of apolipoprotein (APOE) epsilon4 status on the
      cognitive and behavioural functions usually impaired after moderate and severe
      traumatic brain injury (TBI). METHODS: In all, 77 patients with TBI selected from
      140 consecutive admissions were genotyped for APOE. Each patient was subjected to
      neuropsychological and neurobehavioural assessment at least 6 months after
      injury. RESULTS: Performance of participants carrying the epsilon4 allele was
      notably worse on verbal memory (Auditory Verbal Learning Test), motor speed, fine
      motor coordination, visual scanning, attention and mental flexibility (Grooved
      Pegboard, Symbol Digit Modalities Test and part B of the Trail Making Test) and
      showed considerably more neurobehavioural disturbances (Neurobehavioral Rating
      Scale-Revised) than the group without the epsilon4 allele. CONCLUSIONS: In
      particular, performance on neuropsychological tasks that are presumed to be
      related to temporal lobe, frontal lobe and white matter integrity is worse in
      patients with the APOE epsilon4 allele than in those without it. More
      neurobehavioural disturbances are observed in APOE epsilon4 carriers than in APOE
      epsilon2 and epsilon3 carriers.

PMID- 16614012
TI  - Pain after stroke: a neglected issue.

PMID- 16614013
TI  - Can severely disabled patients benefit from in-patient neurorehabilitation for
      acquired brain injury?

PMID- 16614011
TI  - Positive effects of tertiary centres for amyotrophic lateral sclerosis on outcome
      and use of hospital facilities.
AB  - OBJECTIVE: To evaluate the effects of tertiary centres for amyotrophic lateral
      sclerosis (ALS) on ALS outcome and the use of hospital facilities. METHODS: The
      study was based on the data of an epidemiological, prospective, population-based
      register on ALS (Piemonte and Valle d'Aosta Register for amyotrophic lateral
      sclerosis, PARALS). The 221 patients recruited between 1995 and 1996 were
      prospectively followed up for outcome and use of hospital-based services.
      RESULTS: In all, 97 patients were followed up by tertiary ALS centres and 124 by
      general neurological clinics. Patients followed up by tertiary ALS centres were
      found to be 4 years younger and underwent percutaneous endoscopic gastronomy and
      non-invasive positive-pressure ventilation more often. Patients followed up by
      tertiary ALS centres were found to have a considerably longer median survival
      time (1080 v 775 days), even when stratifying by age, site of onset and
      respiratory function at diagnosis. In Cox multivariate analysis, attending a
      tertiary ALS centre was observed to be an independent positive prognostic factor.
      Moreover, patients attending a tertiary ALS centre were admitted to hospital less
      often (1.2 v 3.3) and were more frequently admitted for planned interventions.
      Conversely, patients followed up by general neurological clinics were more
      frequently admitted for acute events. Also, the hospital stay was considerably
      shorter for patients attending tertiary ALS centres (5.8 v 12.4 days).
      CONCLUSIONS: Improved survival was seen in patients with ALS attending tertiary
      ALS centres, independently from all other known prognostic factors, possibly
      through a better implementation of supportive treatments. Moreover, because of
      these centres, the hospitalisation rate was markedly reduced, thus offering a
      cost-effective service to patients with ALS and to the community as a whole.

PMID- 16614014
TI  - Better scoring for better care?

PMID- 16614015
TI  - Endovascular management of unruptured intracranial aneurysms.
AB  - Endovascular coil embolisation is increasingly used to treat unruptured
      intracranial aneurysms (UIA). Endovascular coil embolisation of UIA is associated
      with a 5-10% risk of morbidity and nearly zero mortality from the procedure.
      Complete or near complete occlusion is usually achieved in >90% of cases, and
      endovascular therapy seems to reduce the risk of future rupture significantly.
      Specific selection criteria for endovascular embolisation and novel approaches to
      endovascular treatment of aneurysms are discussed. Endovascular therapy appears
      to be a safe and effective treatment for selected UIA. Treatment failure rates
      will probably decrease with greater experience and advances in techniques and
      devices. Further study with long term follow up, however, is still necessary to
      characterise the efficacy, durability, and cost efficiency of endovascular
      treatment of UIA.

PMID- 16614016
TI  - The Lille apathy rating scale (LARS), a new instrument for detecting and
      quantifying apathy: validation in Parkinson's disease.
AB  - BACKGROUND: Apathy is usually defined as reduced interest and participation in
      various activities. It is a frequent consequence of neurological and psychiatric
      disorders. Although various scoring methods have been proposed, there is a lack
      of validated, standardised instruments for detecting apathy and assessing its
      severity. OBJECTIVE: To develop an apathy rating scale using a structured
      standardised interview capable of distinguishing between the condition's various
      features. METHODS: The Lille Apathy Rating Scale (LARS) is based on a structured
      interview. It includes 33 items, divided into nine domains. Responses are scored
      on a dichotomous scale. The participants used to validate the scale consisted of
      159 patients with probable Parkinson's disease and 58 healthy control subjects.
      The Marin Apathy Scale, the Montgomery and Asberg Depression Rating Scale, and
      the Mattis Dementia Rating Scale were also administered. RESULTS: Principal
      component analysis showed that the LARS probed a single construct which forms the
      root of an oblique factor structure reflecting four dimensions: intellectual
      curiosity, self awareness, emotion, and action initiation. The main psychometric
      properties of the LARS (internal consistency, inter-rater and test-retest
      reliability) were satisfactory. Concurrent validity was evaluated by reference to
      the Marin scale and to judgements provided by expert clinicians. CONCLUSIONS:
      Standard validity indices showed that the LARS is sensitive and capable of
      distinguishing between apathy and depression. As a screening tool, the scale is
      able to support dichotomous judgements accurately and, when greater measurement
      sensitivity is required, also determine the severity of apathy within a four
      category classification.

PMID- 16614017
TI  - Motor subtype and cognitive decline in Parkinson's disease, Parkinson's disease
      with dementia, and dementia with Lewy bodies.
AB  - BACKGROUND: A previous cross sectional study found over-representation of a
      postural instability gait difficulty (PIGD) motor subtype in Parkinson's disease
      patients with dementia (PDD) and dementia with Lewy bodies (DLB), compared with
      Parkinson's disease (PD). AIMS: (1) To examine rates of cognitive and motor
      decline over two years in PD (n=40), PDD (n=42) and DLB (n=41) subjects, compared
      with age matched controls (n=41), (2) to record whether motor phenotypes of PD,
      PDD, and DLB subjects changed during the study, (3) to find out if cognitive and
      motor decline in PD was associated with baseline motor subtype, and (4) to report
      the incidence of dementia in PD patients in relation to baseline motor subtype.
      RESULTS: Most of PDD and DLB participants were PIGD subtype at baseline
      assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes
      were more evenly represented. Cognitive decline over two years was greater in PDD
      and DLB groups (mean decline in MMSE -4.5 and -3.9, respectively), compared with
      PD (-0.2) and controls (-0.3). There was an association between PIGD subtype and
      increased rate of cognitive decline within the PD group. Of 40 PD patients, 25%
      of the 16 PIGD subtype developed dementia over two years, compared with none of
      the 18 TD or six indeterminate phenotype cases (chi2=6.7, Fisher's exact test
      p<0.05). CONCLUSION: A PIGD motor subtype is associated with a faster rate of
      cognitive decline in PD and may be considered a risk factor for incident dementia
      in PD.

PMID- 16614018
TI  - Is NAA reduction in normal contralateral cerebral tissue in stroke patients
      dependent on underlying risk factors?
AB  - BACKGROUND AND PURPOSE: This retrospective study investigated the dependence of N
      acetyl aspartate (NAA) ratios on risk factors for cerebral vasculopathy such as
      sex, age, hypertension, diabetes mellitus, carotid stenosis, and dyslipidaemia,
      which may have affected brain vessels and induced metabolic brain abnormalities
      prior to stroke. We hypothesise that in stroke patients metabolic alterations in
      the apparently normal contralateral brain are dependent on the presence or not of
      such risk factors. METHODS: Fifty nine patients (31 male, 28 female: 58.8+/-16.1
      years old) with cortical middle cerebral artery (MCA) territory infarction were
      included. Long echo time chemical shift imaging spectroscopy was carried out on a
      Siemens 1.5 T Magnetom Vision scanner using a multi-voxel PRESS technique.
      Metabolite ratios (NAA/choline, NAA/creatine, lactate/choline, etc) were studied
      using uni- and multivariate analyses with respect to common risk factors. The
      influence of age, stroke lesion size, and time since stroke was studied using a
      linear regression approach. RESULTS: Age, sex, and hypertension all appeared to
      individually influence metabolite ratios, although only hypertension was
      significant after multivariate analysis. In both basal ganglia and
      periventricular white matter regions in apparently normal contralateral brain,
      the NAA/choline ratio was significantly lower in hypertensive (1.37+/-0.16 and
      1.50+/-0.19, respectively) than in normotensive patients (1.72+/-0.19 and 1.85+/
      0.15, respectively). CONCLUSIONS: Regarding MCA infarction, contralateral tissue
      remote from the lesion behaves abnormally in the presence of hypertension, the
      NAA ratios in hypertensive patients being significantly lower. These data suggest
      that hypertension may compromise the use of contralateral tissue data as a
      reference for comparison with ischaemic tissue.

PMID- 16614019
TI  - Longitudinal course of depression symptoms in multiple sclerosis.
AB  - BACKGROUND: Despite the high lifetime prevalence of depression in multiple
      sclerosis (MS), its longitudinal course is poorly understood. OBJECTIVE: To
      examine the longitudinal course of and reliable change in different depression
      symptom clusters in MS, and the longitudinal association of interferon beta
      treatment and coping with depression symptoms. METHODS: 53 MS patients were
      examined at two time points three years apart on the Beck Depression Inventory
      (BDI) and the Chicago Multiscale Depression Inventory (CMDI). RESULTS:
      Correlations from time 1 to time 2 for BDI, CMDI-total, CMDI-evaluative scale,
      and CMDI-vegetative scale were all highly significant, and reliable change
      indices reflected little change over time. In contrast, the correlation over time
      for the CMDI-mood scale was significantly lower (p<0.05) than the CMDI-evaluative
      and CMDI-vegetative scale correlations, and over 40% of patients showed reliable
      change. Patients who improved in their mood showed increased use of active
      coping, while patients who worsened showed decreased active coping strategies;
      the latter were also significantly more likely to have been taking interferon
      beta drugs at both time points than patients who did not change in their mood
      functioning. CONCLUSIONS: Mood symptoms of depression are significantly more
      variable over time than neurovegetative or negative evaluative symptoms in MS
      patients. Decreased use of active coping strategies may put patients at risk of
      increased depressed mood, whereas increased use of active coping may result in
      decreased depressed mood longitudinally. Interferon beta use may put patients at
      risk of increases in depressed mood.

PMID- 16614020
TI  - Prognosis of status epilepticus: role of aetiology, age, and consciousness
      impairment at presentation.
AB  - BACKGROUND: Identification of outcome-predictive factors could lower risk of
      under- or over-treatment in status epilepticus (SE). Older age and acute
      symptomatic aetiology have been shown to predict mortality, but other variables
      are controversial and level of consciousness has received relatively little
      attention. The objective of this study was to assess variables predictive of
      mortality, particularly those available at presentation. METHODS: The discharge
      database (1997-2004) of two university hospitals was screened for adult patients
      with EEG confirmed SE, excluding cerebral anoxia. Outcome at discharge
      (mortality, return to baseline clinical conditions) was analysed in relation to
      demographics, clinical features, and aetiology. Aetiologies were also classified
      based on whether or not they were potentially fatal independently of SE. RESULTS:
      Mortality was 15.6% among 96 patients with a first SE episode, 10 of whom also
      experienced recurrent SE during the study period. Eleven other patients had only
      recurrent SE. Mortality was 4.8% among these 21 patients with recurrent SE.
      Return to baseline condition was more frequent after recurrent than incident SE
      (p=0.02). For the first SE episode, death was associated with potentially fatal
      aetiology (p=0.01), age>or=65 (p=0.02), and stupor or coma at presentation
      (p=0.04), but not with gender, history of epilepsy, SE type, or time to
      treatment>or=1 h. CONCLUSIONS: At initial evaluation, older age and marked
      impairment of consciousness are predictive of death. Surviving a first SE episode
      could lower the mortality and morbidity of subsequent episodes, suggesting that
      underlying aetiology, rather than SE per se, is the major determinant of outcome.

PMID- 16614021
TI  - Ictal symptoms of anxiety, avoidance behaviour, and dissociation in patients with
      dissociative seizures.
AB  - OBJECTIVE: To examine anxiety related seizure symptoms and avoidance behaviour in
      adults with dissociative (psychogenic non-epileptic) seizures (DS) in comparison
      with a group suffering from partial epilepsy. METHODS: 25 DS and 19 epilepsy
      patients completed an attack symptom measure, the hospital anxiety and depression
      scale, the dissociative experiences scale, and the fear questionnaire. RESULTS:
      DS patients reported the presence of significantly greater numbers of somatic
      symptoms of anxiety during their attacks than the epilepsy group, despite not
      reporting subjectively higher levels of anxiety. The DS patients also reported
      higher levels of agoraphobic-type avoidance behaviour than the epilepsy group.
      Measures of dissociation were higher in the DS group, who also reported greater
      symptoms of depression. CONCLUSIONS: The findings support a model whereby DS
      occur as a paroxysmal, dissociative response to heightened arousal in the absence
      of raised general anxiety levels. The model has practical implications for
      clinical assessment and treatment: in clinical practice, inquiry about these
      symptoms may help in the diagnosis of DS; with respect to treatment, the anxiety
      related symptoms and avoidance behaviour prevalent in DS are a potential focus
      for a cognitive behavioural approach analogous to that used in the treatment of
      other anxiety disorders.

PMID- 16614022
TI  - Reduction in hypothalamic 1H-MRS metabolite ratios in patients with cluster
      headache.
AB  - OBJECTIVE: To determine the 1H-MR spectroscopic (MRS) findings in the
      hypothalamus in patients with episodic cluster headache. METHODS: 47 patients
      were recruited with episodic cluster headache (35 in cluster period and 12 in
      remission), 21 normal controls, and 16 patients with chronic migraine. The
      hypothalamic 1H-MRS metabolite ratio changes in patients with cluster headache
      were evaluated and compared with results in the normal controls as well as
      patients with chronic migraine. Seven patients in the cluster period group
      underwent a follow up hypothalamic MRS study five to six months after remission.
      RESULTS: In patients with cluster headache, the hypothalamic N-acetylaspartate
      (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were similar between those in
      cluster period and in remission. As a group, both NAA/Cr and Cho/Cr levels were
      significantly lower in patients with cluster headache in comparison with either
      the control or chronic migraine groups. In those with a follow up MRS study, the
      levels of metabolite ratios did not differ between the cluster and remission
      periods. CONCLUSIONS: This study provides evidence of persistent biochemical
      change of the hypothalamus in patients with episodic cluster headache. Low levels
      of NAA/Cr and Cho/Cr suggest that cluster headache might be related to both
      neuronal dysfunction and changes in the membrane lipids in the hypothalamus.

PMID- 16614023
TI  - Efficiency of specialist rehabilitation in reducing dependency and costs of
      continuing care for adults with complex acquired brain injuries.
AB  - OBJECTIVES: To examine functional outcomes from a rehabilitation programme and to
      compare two methods for evaluating cost efficiency of rehabilitation in patients
      with severe complex disability. SUBJECTS AND SETTING: Two hundred and ninety
      seven consecutive admissions to a specialist inpatient rehabilitation unit
      following severe acquired brain injury. METHODS: Retrospective analysis of
      routinely collected data, including the Functional Independence Measure (FIM),
      Barthel Index, and Northwick Park Dependency Score and Care Needs Assessment
      (NPDS/NPCNA), which provides a generic estimation of dependency, care hours. and
      weekly cost of continuing care in the community. Patients were analysed in three
      groups according to dependency on admission: "low" (NPDS<10 (n=83)); "medium"
      (NPDS10-24 (n=112)); "high" (NPDS>24 (n=102)). RESULTS: Mean length of stay (LOS)
      112 (SD 66) days. All groups showed significant reduction in dependency between
      admission and discharge on all measures (paired t tests: p<0.001). Mean reduction
      in "weekly cost of care" was greatest in the high dependency group at pound639
      per week (95% CI 488 to 789)), as compared with the medium (pound323/week (95% CI
      217 to 428)), and low (pound111/week (95% CI 42 to 179)) dependency groups.
      Despite their longer LOS, time taken to offset the initial cost of rehabilitation
      was only 16.3 months in the high dependency group, compared with 21.5 months
      (medium dependency) and 38.8 months (low dependency). FIM efficiency (FIM
      gain/LOS) appeared greatest in the medium dependency group (0.25), compared with
      the low (0.17) and high (0.16) dependency groups. CONCLUSIONS: The NPDS/NPCNA
      detected changes in dependency potentially associated with substantial savings in
      the cost of ongoing care, especially in high dependency patients. Floor effects
      in responsiveness of the FIM may lead to underestimation of efficiency of
      rehabilitation in higher dependency patients.

PMID- 16614024
TI  - Myxoedema and Sir William Withey Gull (1816-1890).

PMID- 16614025
TI  - Disability in young people and adults after head injury: 5-7 year follow up of a
      prospective cohort study.
AB  - BACKGROUND: Improvement 1-2 years after head injury is well established but the
      pattern thereafter is unclear. Past studies have not examined representative head
      injury populations and typically report findings in terms of functioning across
      social, psychological, neurobehavioural, or cognitive domains rather than global
      outcome. OBJECTIVE: To determine the late outcome of a representative cohort of
      participants admitted to hospital after a head injury 5-7 years previously and to
      identify early and late factors correlating with persisting disability and change
      between one and 5-7 years. METHODS: A representative cohort of head injured
      people whose outcome one year after injury was reported previously, were followed
      up 5-7 years after injury. Participants were assessed using structured and
      validated measures of global outcome (Glasgow Outcome Scale Extended), cognitive
      impairment, psychological wellbeing, health status, and social factors. RESULTS:
      Of 475 survivors studied at one year, 115 (24%) had died by seven years. In
      survivors at 5-7 years, disability remained frequent (53%); and the rate, similar
      to that found at one year (57%). Sixty three participants (29%) had improved but
      55 (25%) deteriorated. The persistence of disability and its development after
      previous recovery each showed stronger associations with indices of depression,
      anxiety, and low self-esteem than with initial severity of injury or persisting
      cognitive impairment. CONCLUSIONS: Admission to hospital after head injury is
      followed 5-7 years later by disability in a high proportion of survivors.
      Persistence of disability and development of new disability are strongly
      associated with psychosocial factors that may be open to remediation, even late
      after injury.

PMID- 16614026
TI  - Time dependent validity in the diagnosis of brain death using transcranial
      Doppler sonography.
AB  - OBJECTIVE: To evaluate the validity of transcranial Doppler (TCD) in confirming
      brain death from various pathological conditions. METHODS: An observational case
      control study over a 2.5 year period, in which transcranial Doppler (TCD)
      examinations were done on 101 comatose patients for confirmation of brain death.
      Between October 2002 to May 2005, 44 clinically diagnosed brain death cases (29
      male, 15 female; mean (SD) age, 46.5 (19.5) years; Glasgow Coma Scale (GCS)
      score, 3.0 (0.0)) and 57 controls (36 male, 21 female; age 48.1 (16.5) years;
      mean GCS, 4.9 (1.7)) were examined. Reverse diastolic flow, very small systolic
      spikes, or no signals were considered characteristic of cerebral circulatory
      arrest. RESULTS: The sensitivity and specificity of TCD examination of both the
      basilar artery and the middle cerebral arteries (MCAs) in confirming brain death
      were 77.2% and 100%, respectively. The sensitivity of TCD-diagnosed brain death
      increased with elapsed time. There was a trend for the basilar artery to have
      greater sensitivity (86.4% v 77.2%), higher positive predictive value (90.5% v
      85.1%), and fewer false negatives (14% v 23.7%) than the MCAs for diagnosing
      brain death (all NS). The consistency of the basilar artery and the MCAs for
      diagnosing brain death was significant (kappa=0.877, p<0.001 and kappa=0.793,
      p<0.001, respectively). CONCLUSIONS: TCD can be a confirmatory tool for
      diagnosing brain death. The validity of TCD diagnosed brain death depends on the
      time lapse between brain death and the performance of TCD. TCD of both the
      basilar artery and the MCAs showed significant consistency in brain death
      diagnosis.

PMID- 16614027
TI  - Sensorimotor dysfunction of grasping in schizophrenia: a side effect of
      antipsychotic treatment?
AB  - BACKGROUND: Antipsychotic treatment in schizophrenia is frequently associated
      with extrapyramidal side effects. Objective behavioural measures to evaluate the
      severity of extrapyramidal side effects in the clinical setting do not exist.
      OBJECTIVES: This study was designed to investigate grasping movements in five
      drug naive and 13 medicated subjects with schizophrenia and to compare their
      performance with that of 18 healthy control subjects. Deficits of grip force
      performance were correlated with clinical scores of both parkinson-like motor
      disability and psychiatric symptom severity METHODS: Participants performed
      vertical arm movements with a handheld instrumented object and caught a weight
      that was dropped into a handheld cup either expectedly from the opposite hand or
      unexpectedly from the experimenter's hand. The scaling of grip force and the
      temporospatial coupling between grip and load force profiles was analysed. The
      psychiatric symptom severity was assessed by the positive and negative symptom
      score of schizophrenia and the brief psychiatric rating scale. Extrapyramidal
      symptoms were assessed by the unified Parkinson's disease rating scale. RESULTS:
      Drug naive subjects with schizophrenia performed similar to healthy controls. In
      contrast, medicated subjects with schizophrenia exhibited excessive grip force
      scaling and impaired coupling between grip and load force profiles. These
      performance deficits were strongly correlated with the severity of both
      extrapyramidal side effects related to antipsychotic therapy and negative
      symptoms related to the underlying pathology. CONCLUSIONS: These data provide
      preliminary evidence that deficits of sensorimotor performance in schizophrenia
      are, at least in part, related to the side effects of antipsychotic treatment.
      The investigation of grasping movements may provide a sensitive measure to
      objectively evaluate extrapyramidal side effects related to antipsychotic
      therapy.

PMID- 16614028
TI  - Interaction of somatoform and vestibular disorders.
AB  - BACKGROUND: The high coincidence of organic vestibular and somatoform vertigo
      syndromes has appeared to support pathogenic models showing a strong linkage
      between them. It was hypothesised that a persisting vestibular dysfunction causes
      the development of anxiety disorders. OBJECTIVE: To determine the relation
      between vestibular deficits and somatoform vertigo disorders in an
      interdisciplinary prospective study. METHODS: Participants were divided into
      eight diagnostic groups: healthy volunteers (n=26) and patients with benign
      paroxysmal positioning vertigo (BPPV, n=11), vestibular neuritis (n=11),
      Meniere's disease (n=7), vestibular migraine (n=15), anxiety (n=23), depression
      (n=12), or somatoform disorders (n=22). Neuro-otological diagnostic procedures
      included electro-oculography with rotatory and caloric testing, orthoptic
      examination with measurements of subjective visual vertical (SVV) and ocular
      torsion, and a neurological examination. Psychosomatic diagnostic procedures
      comprised interviews and psychometric instruments. RESULTS: Patients with BPPV
      (35.3%) and with vestibular neuritis (52.2%) had pathological test values on
      caloric irrigation (p<0.001). Otolith dysfunction with pathological tilts of SVV
      and ocular torsion was found only in patients with vestibular neuritis (p<0.001).
      Patients with Meniere's disease, vestibular migraine, and psychiatric disorders
      showed normal parameters for vestibular testing but pathological values for
      psychometric measures. There was no correlation between pathological neurological
      and pathological psychometric parameters. CONCLUSIONS: High anxiety scores are
      not a result of vestibular deficits or dysfunction. Patients with Meniere's
      disease and vestibular migraine but not vestibular deficits showed the highest
      psychiatric comorbidity. Thus the course of vertigo syndromes and the possibility
      of a pre-existing psychopathological personality should be considered pathogenic
      factors in any linkage between organic and psychometric vertigo syndromes.

PMID- 16614029
TI  - Prevalence of the LRRK2 G2019S mutation in a UK community based idiopathic
      Parkinson's disease cohort.
AB  - The LRRK2 G2019S mutation is the commonest genetic cause of Parkinson's disease
      (PD) identified to date, although estimates of its prevalence in idiopathic
      disease vary considerably. Our objectives were to determine G2019S mutation
      frequency in an unselected, community based cohort of idiopathic PD cases from
      the UK and to describe phenotypic characteristics among carriers. The mutation
      was present in two of 519 cases (0.4%) and none of 887 control individuals. The
      true prevalence of the mutation in idiopathic disease, its penetrance, and the
      phenotypic heterogeneity of associated cases have important implications for
      genetic screening in the clinical field.

PMID- 16614030
TI  - Cognitive functioning in sporadic amyotrophic lateral sclerosis: a six month
      longitudinal study.
AB  - OBJECTIVE: To observe changes in cognition over six months in subjects with
      recently diagnosed sporadic amyotrophic lateral sclerosis (ALS). METHODS: The
      study used a between-group and within-group longitudinal design. Nineteen ALS
      subjects and eight matched caregivers were recruited to participate in baseline
      neuropsychological assessments that were repeated six months later. Between group
      comparisons for these variables were undertaken at baseline and six months later.
      Within group/across time comparisons for these variables were carried out for
      both groups. Individual analyses for the neuropsychological variables using z
      scores were done for the ALS subjects using their baseline performance as the
      basis for comparison with their six month performance. RESULTS: The between-group
      and within-group comparisons did not show significant differences in cognitive
      function over time. In individual analyses, however, seven of 19 ALS subjects
      (36.84%) developed abnormal neuropsychological performance over six months.
      CONCLUSIONS: Early in the disease course, over one third of the ALS subjects
      developed cognitive deficits over six months. These findings support the
      hypothesis that cognitive deficits in ALS become more prominent over time.

PMID- 16614031
TI  - Cardiomyopathy in motor neuron diseases.
AB  - OBJECTIVE: Myocardial involvement in motor neuron diseases (MND) is an uncommon
      feature. In amyotrophic lateral sclerosis (ALS) abnormalities of the autonomic
      nervous system affecting cardiac function have been described, for the hereditary
      spastic paraplegias (HSP) comparable manifestations are unknown. This study
      observed ALS and HSP patients with coexisting cardiomyopathy without major
      cardial risk factors. METHODS: Four patients with definite ALS and two pHSP
      patients. In all patients detailed clinical, cardiological, electrophysiological
      and laboratory data were analysed. In two ALS patients skeletal muscle biopsy was
      performed. RESULTS: In all investigated MND patients cardiomyopathy was present.
      Beside hyperlipoproteinaemia and mild hypertension in one case, none of the
      patients showed major cardiovascular risk factors. There was no evidence for a
      secondary cause of cardiomyopathy like coronary heart disease, myocarditis, or
      mitochondrial damage mimicking MND. CONCLUSION: This report could not conclude
      that the occurrence of cardiomyopathy is rare logically. Although an underlying
      pathophysiological cause was not obvious, it is proposed that in all MND patients
      a routine cardiological evaluation should be performed.

PMID- 16614032
TI  - Neurological picture. Temporal arteritis or phlebitis?

PMID- 16614033
TI  - Disruption of sitting balance after stroke: influence of spoken output.
AB  - OBJECTIVES: To identify the extent of dual task interference between cognitive
      and motor tasks, (cognitive motor interference (CMI)) in sitting balance during
      recovery from stroke; to compare CMI in sitting balance between stroke and non
      stroke groups; and to record any changes to CMI during sitting that correlate
      with functional recovery. METHOD: 36 patients from stroke rehabilitation settings
      in three NHS trusts. Healthy control group: 21 older volunteers. Measures of
      seated postural sway were taken in unsupported sitting positions, alone, or
      concurrently with either a repetitive utterance task or an oral word category
      generation task. Outcome measures were variability of sway area, path length of
      sway, and the number of valid words generated. RESULTS: Stroke patients were
      generally less stable than controls during unsupported sitting tasks. They showed
      greater sway during repetitive speech compared with quiet sitting, but did not
      show increased instability to posture between repetitive speech and word category
      generation. When compared with controls, stroke patients experienced greater dual
      task interferences during repetitive utterance but not during word generation.
      Sway during repetitive speech was negatively correlated with concurrent function
      on the Barthel ADL index. CONCLUSIONS: The stroke patients showed postural
      instability and poor word generation skills. The results of this study show that
      the effort of verbal utterances alone was sufficient to disturb postural control
      early after stroke, and the extent of this instability correlated with
      concomitant Barthel ADL function.

PMID- 16614034
TI  - Seasonal variability in spontaneous cervical artery dissection.
AB  - We examined the seasonal variability of spontaneous cervical artery dissection
      (sCAD) by analysing prospectively collected data from 352 patients with 380 sCAD
      (361 symptomatic sCAD; 305 carotid and 75 vertebral artery dissections) admitted
      to two university hospitals with a catchment area of 2,200,000 inhabitants
      between 1985 and 2004. Presenting symptoms and signs of the 380 sCAD were
      ischaemic stroke in 241 (63%), transient ischaemic attack in 40 (11%), retinal
      ischemia in seven (2%), and non-ischaemic in 73 (19%) cases; 19 (5%) were
      asymptomatic sCAD. A seasonal pattern, with higher frequency of sCAD in winter
      (31.3%; 95% confidence interval (CI): 26.5 to 36.4; p=0.021) compared to spring
      (25.5%; 95% CI: 21.1 to 30.3), summer (23.5%; 95% CI: 19.3 to 28.3), and autumn
      (19.7%; 95% CI: 15.7 to 24.1) was observed. Although the cause of seasonality in
      sCAD is unclear, the winter peaks of infection, hypertension, and aortic
      dissection suggest common underlying mechanisms.

PMID- 16614035
TI  - Transient hemiageusia in cerebrovascular lateral pontine lesions.
AB  - Knowledge of human central taste pathways is largely based on textbook
      (anatomical dissections) and animal (electrophysiology in vivo) data. It is only
      recently that further functional insight into human central gustatory pathways
      has been achieved. Magnetic resonance imaging studies, especially selective
      imaging of vascular, tumoral, or inflammatory lesions in humans has made this
      possible. However, some questions remain, particularly regarding the exact
      crossing site of human gustatory afferences. We present a patient with a pontine
      stroke after a vertebral artery thrombosis. The patient had infarctions in areas
      supplied by the anterior inferior cerebellar artery and showed vertical diplopia,
      right sided deafness, right facial palsy, and transient hemiageusia. A review of
      the sparse literature of central taste disorders and food preference changes
      after strokes with a focus on hemiageusia cases is provided. This case offers new
      evidence suggesting that the central gustatory pathway in humans runs
      ipsilaterally within the pons and crosses at a higher, probably midbrain level.
      In patients with central lesions, little attention has been given to taste
      disorders. They may often go unnoticed by the physician and/or the patient.
      Central lesions involving taste pathways seem to generate perceptions of
      quantitative taste disorders (hemiageusia or hypogeusia), in contrast to
      peripheral gustatory lesions that are hardly recognised as quantitative but
      sometimes as qualitative (dysgeusia) taste disorders by patients.

PMID- 16614036
TI  - Transverse myelitis due to trypanosomiasis in a middle aged Tanzanian man.
AB  - We report the case of a middle aged Tanzanian man who developed a spinal cord
      syndrome over 6 weeks, along with a mild encephalopathy. Investigations ruled out
      the usual major causes of such a syndrome in our setting in northern Tanzania.
      Examination of his cerebrospinal fluid revealed trypanosomes, and he made a slow
      but dramatic improvement after a full course of suramine and melarsoprol. We
      postulate that he had a transverse myelitis due to African trypanosomiasis, a
      rare and barely recognised cause.

PMID- 16614038
TI  - Orgasmic headache and middle cerebral artery dissection.
AB  - A patient with a 20 year history of primary orgasmic headache is described who,
      after suffering an unusually severe episode of orgasmic headache was found to
      have a middle cerebral artery dissection. This unusual association of primary and
      secondary orgasmic headache emphasises the need for a thorough diagnostic
      examination when the orgasmic headache differs from that of previous episodes or
      is associated with neurological symptoms.

PMID- 16614037
TI  - Diffusion tensor magnetic resonance imaging at 3.0 tesla shows subtle cerebral
      grey matter abnormalities in patients with migraine.
AB  - BACKGROUND AND OBJECTIVE: Diffusion tensor (DT) magnetic resonance imaging (MRI)
      has the potential to disclose subtle abnormalities in the brain of migraine
      patients. This ability may be increased by the use of high field magnets. A DT
      MRI on a 3.0 tesla scanner was used to measure the extent of tissue damage of the
      brain normal appearing white (NAWM) and grey matter in migraine patients with T2
      visible abnormalities. METHODS: Dual echo, T1 weighted and DT MRI with diffusion
      gradients applied in 32 non-collinear directions were acquired from 16 patients
      with migraine and 15 sex and age matched controls. Lesion load on T2 weighted
      images was measured using a local thresholding segmentation technique, and brain
      atrophy assessed on T1 weighted images using SIENAx. Mean diffusivity and
      fractional anisotropy histograms of the NAWM and mean diffusivity histograms of
      the grey matter were also derived. RESULTS: Brain atrophy did not differ between
      controls and patients. Compared with healthy subjects, migraine patients had
      significantly reduced mean diffusivity histogram peak height of the grey matter
      (p=0.04). No diffusion changes were detected in patients' NAWM. In migraine
      patients, no correlation was found between T2 weighted lesion load and brain DT
      histogram derived metrics, whereas age was significantly correlated with grey
      matter mean diffusivity histogram peak height (p=0.05, r=-0.52). CONCLUSIONS: DT
      MRI at high field strength discloses subtle grey matter damage in migraine
      patients, which might be associated with cognitive changes in these patients.

PMID- 16614039
TI  - Effect of neck flexion on F wave, somatosensory evoked potentials, and magnetic
      resonance imaging in Hirayama disease.
AB  - BACKGROUND: Flexion myelopathy is one of the suggested mechanism for Hirayama
      disease (HD) but simultaneous radiological and neurophysiological evaluation is
      lacking. This study therefore evaluates the effect of neck flexion in HD using
      somatosensory evoked potentials (SEPs), F waves, and magnetic resonance imaging
      (MRI). METHOD: Eight HD patients and seven matched controls were subjected to
      median and ulnar F wave (minimal latency, FM ratio, persistence, and
      chronodispersion), and SEPs evaluating N9, N13, and N20 potentials in neutral and
      neck flexion. Spinal MRI was carried out in neutral and neck flexion and
      evaluated for cord atrophy, signal changes, cord compression, posterior epidural
      tissue, and loss of dural attachment. RESULTS: The patients were aged 19 to 30
      years. Minimal F latency, FM ratio, persistence, and chronodispersion in neutral
      and neck flexion did not show any change nor was there any change in N13 latency
      and amplitude on median and ulnar SEPs. The difference in these parameters in
      neutral and neck flexion were also not significant in HD compared with controls.
      The change in N13 was also not related to loss of dural attachment and posterior
      epidural tissue. CONCLUSION: Neck flexion does not produce significant changes in
      N13 and F wave parameters and is not related to dynamic MRI changes. The other
      mechanisms for HD should therefore be explored.

PMID- 16614040
TI  - Neurological picture. Spinal endoscopic biopsy in the diagnosis of central
      nervous system neurosarcoidosis.

PMID- 16614041
TI  - Diffuse lesion in the splenium of the corpus callosum in patients with methyl
      bromide poisoning.

PMID- 16614042
TI  - Wasp sting induced autoimmune neuromyotonia.

PMID- 16614043
TI  - Left hemianomia of musical symbols caused by callosal infarction.

PMID- 16614044
TI  - Leucocytoclastic vasculitic neuropathy diagnosed by biopsy of normal appearing
      skin.

PMID- 16614045
TI  - Pulmonary arteriovenous fistulae thrombosis responsible for recurrent stroke.

PMID- 16614046
TI  - Hypothyroidism and nemaline myopathy in an adult.

PMID- 16614047
TI  - Parkinsonism in type 1 Gaucher's disease.

PMID- 16614048
TI  - Acute renal response to LPS: impaired arginine production and inducible nitric
      oxide synthase activity.
AB  - We have previously shown in rats that lipopolysaccharide (LPS) causes both
      decreased renal perfusion and kidney arginine production before nitric oxide (NO)
      synthesis, resulting in a >30% reduction in plasma arginine. To clarify the early
      phase effects of LPS, we asked the following two questions: 1) is the rapid
      change in renal arginine production after LPS simply the result of decreased
      substrate (i.e., citrulline) delivery to the kidney or due to impaired uptake and
      conversion and 2) is the systemic production of NO limited by plasma arginine
      availability after LPS? Arterial and renal vein plasma was sampled at 30-min
      intervals from anesthetized rats with or without citrulline or arginine (2
      micromol.min(-1).kg(-1) iv) a dose with no effect on MAP, renal function, or NO
      production. Exogenous citrulline was quickly converted to arginine by the kidney,
      resulting in plasma levels similar to equimolar arginine infusion. Also, the
      increase in citrulline uptake resulted primarily from increased filtered load and
      reabsorption. In a separate series, citrulline was infused after LPS
      administration, verifying that citrulline uptake and conversion persists during
      impaired kidney function. Last, in rats given LPS, the elevation of plasma
      arginine had no discernable impact on mean arterial pressure, kidney function, or
      systemic NO production. This work demonstrates how arginine synthesis is normally
      "substrate limited" and explains how impaired kidney perfusion quickly results in
      decreased plasma arginine. However, contrary to in vitro studies, the significant
      reduction in extracellular arginine during the early phase response to LPS in
      vivo is not functionally rate limiting for NO production.

PMID- 16614049
TI  - Cloning and functional characterization of a second urea transporter from the
      kidney of the Atlantic stingray, Dasyatis sabina.
AB  - The cloning of cDNAs encoding facilitated urea transporters (UTs) from the
      kidneys of the elasmobranchs indicates that in these fish renal urea reabsorption
      occurs, at least in part, by passive processes. The previously described
      elasmobranch urea transporter clones from shark (shUT) and stingray (strUT-1)
      differ from each other primarily because of the COOH-terminus of the predicted
      strUT-1 translation product being extended by 51-amino acid residues compared
      with shUT. Previously, we noted multiple UT transcripts were present in stingray
      kidney. We hypothesized that a COOH terminally abbreviated UT isoform, homologous
      to shUT, would also be present in stingray kidney. Therefore, we used 5'/3' rapid
      amplification of cDNA ends to identify a 3'UTR-variant (strUT-1a) of the cDNA
      that encodes (strUT-1), as well as three, 3'UTR-variant cDNAs (strUT-2a,b,c) that
      encode a second phloretin-sensitive, urea transporter (strUT-2). The 5'UTR and
      the first 1,132 nucleotides of the predicted coding region of the strUT-2 cDNAs
      are identical to the strUT-1 cDNAs. The remainder of the coding region contains
      only five novel nucleotides. The strUT-2 cDNAs putatively encode a 379-amino acid
      protein, the first 377 amino acids identical to strUT-1 plus 2 additional amino
      acids. We conclude that 1) a second UT isoform is expressed in the Atlantic
      stingray and that this isoform is similar in size to the UT previously cloned
      from the kidney of the dogfish shark, and 2) at least five transcripts encoding
      the 2 stingray UTs are derived from a single gene product through alternative
      splicing and polyadenylation.

PMID- 16614051
TI  - Intrauterine ethanol exposure results in hypothalamic oxidative stress and
      neuroendocrine alterations in adult rat offspring.
AB  - Prenatal ethanol (EtOH) exposure is associated with low birth weight, followed by
      increased appetite, catch-up growth, insulin resistance, and impaired glucose
      tolerance in the rat offspring. Because EtOH can induce oxidative stress, which
      is a putative mechanism of insulin resistance, and because of the central role of
      the hypothalamus in the regulation of energy homeostasis and insulin action, we
      investigated whether prenatal EtOH exposure causes oxidative damage to the
      hypothalamus, which may alter its function. Female rats were given EtOH by gavage
      throughout pregnancy. At birth, their offspring were smaller than those of non
      EtOH rats. Markers of oxidative stress and expression of neuropeptide Y and
      proopiomelanocortin (POMC) were determined in hypothalami of postnatal day 7
      (PD7) and 3-mo-old (adult) rat offspring. In both PD7 and adult rats, prenatal
      EtOH exposure was associated with decreased levels of glutathione and increased
      expression of MnSOD. The concentrations of lipid peroxides and protein carbonyls
      were normal in PD7 EtOH-exposed offspring, but were increased in adult EtOH
      exposed offspring. Both PD7 and adult EtOH-exposed offspring had normal
      neuropeptide Y and POMC mRNA levels, but the adult offspring had reduced POMC
      protein concentration. Thus only adult offspring preexposed to EtOH had increased
      hypothalamic tissue damage and decreased levels of POMC, which could impair
      melanocortin signaling. We conclude that prenatal EtOH exposure causes
      hypothalamic oxidative stress, which persists into adult life and alters
      melanocortin action during adulthood. These neuroendocrine alterations may
      explain weight gain and insulin resistance in rats exposed to EtOH early in life.

PMID- 16614052
TI  - An arousing, musically enhanced bird song stimulus mediates circadian rhythm
      phase advances in dim light.
AB  - A musically enhanced bird song stimulus presented in the early subjective night
      phase delays human circadian rhythms. This study determined the phase-shifting
      effects of the same stimulus in the early subjective day. Eleven subjects (ages
      18-63 yr; mean +/- SD: 28.0 +/- 16.6 yr) completed two 4-day laboratory sessions
      in constant dim light (<20 lux). They received two consecutive presentations of
      either a 2-h musically enhanced bird song or control stimulus from 0600 to 0800
      on the second and third mornings while awake. The 4-day sessions employing either
      the stimulus or control were counterbalanced. Core body temperature (CBT) was
      collected throughout the study, and salivary melatonin was obtained every 30 min
      from 1900 to 2330 on the baseline and poststimulus/postcontrol nights. Dim light
      melatonin onset and CBT minimum circadian phase before and after stimulus or
      control presentation was assessed. The musically enhanced bird song stimulus
      produced significantly larger phase advances of the circadian melatonin (mean +/-
      SD: 0.87 +/- 0.36 vs. 0.24 +/- 0.22 h) and CBT (1.08 +/- 0.50 vs. 0.43 +/- 0.37
      h) rhythms than the control. The stimulus also decreased fatigue and total mood
      disturbance, suggesting arousing effects. This study shows that a musically
      enhanced bird song stimulus presented during the early subjective day phase
      advances circadian rhythms. However, it remains unclear whether the phase shifts
      are due directly to effects of the stimulus on the clock or are arousal- or dim
      light-mediated effects. This nonphotic stimulus mediates circadian
      resynchronization in either the phase advance or delay direction.

PMID- 16614053
TI  - Ion channel proteins in neuronal temperature transduction: from inferences to
      testable theories of deep-body thermosensitivity.

PMID- 16614054
TI  - Intermediate filament protein nestin is expressed in developing kidney and heart
      and might be regulated by the Wilms' tumor suppressor Wt1.
AB  - Nestin is an intermediate filament protein originally described in neural stem
      cells and a variety of progenitor cells. More recently, nestin was detected in
      rat kidney podocytes. We show here that nestin is expressed in a developmentally
      regulated pattern in the kidney. Nestin was detected by immunohistochemistry in
      the condensing mesenchyme surrounding the ureter, in developing glomeruli, in
      podocytes of the adult kidney, and in a podocyte cell line. Nestin shared a
      striking overlap in expression with the Wilms' tumor suppressor Wt1. Nestin was
      significantly upregulated in a cell line with inducible Wt1 expression upon
      induction of Wt1. Cotransfection experiments in human embryonic kidney cells
      (HEK293) revealed stimulation of a nestin intron 2 enhancer element up to six
      fold by the Wt1(-KTS) splice variant. Nestin expression was significantly reduced
      in an inducible mouse model of glomerular disease. This model is based on
      podocyte-specific overexpression of Pax2 and associated with a loss of Wt1
      expression. Furthermore, also in the developing heart, nestin was found in an
      overlapping pattern with Wt1 in the epicardium and the forming coronary vessels.
      Strikingly, in the hearts of Wt1 knockout mice, nestin was barely detectable
      compared with the hearts of wild-type embryos. Our results show that nestin is
      expressed at different stages of kidney and cardiac development and suggest that
      its expression in these organs might be regulated by the Wilms' tumor suppressor
      Wt1.

PMID- 16614055
TI  - Postnatal environment overrides genetic and prenatal factors influencing
      offspring obesity and insulin resistance.
AB  - There is growing evidence that the postnatal environment can have a major impact
      on the development of obesity and insulin resistance in offspring. We postulated
      that cross-fostering obesity-prone offspring to lean, obesity-resistant dams
      would ameliorate their development of obesity and insulin resistance, while
      fostering lean offspring to genetically obese dams would lead them to develop
      obesity and insulin resistance as adults. We found that obesity-prone pups cross
      fostered to obesity-resistant dams remained obese but did improve their insulin
      sensitivity as adults. In contrast, obesity-resistant pups cross-fostered to
      genetically obese dams showed a diet-induced increase in adiposity, reduced
      insulin sensitivity, and associated changes in hypothalamic neuropeptide,
      insulin, and leptin receptors, which might have contributed to their metabolic
      defects. There was a selective increase in insulin levels and differences in
      fatty acid composition of obese dam milk which might have contributed to the
      increased adiposity, insulin resistance, and hypothalamic changes in obesity
      resistant cross-fostered offspring. These results demonstrate that postnatal
      factors can overcome both genetic predisposition and prenatal factors in
      determining the development of adiposity, insulin sensitivity, and the brain
      pathways that mediate these functions.

PMID- 16614056
TI  - Gastrointestinal and renal responses to water intake in the green-backed
      firecrown (Sephanoides sephanoides), a South American hummingbird.
AB  - To maintain water balance, nectar-feeding vertebrates oscillate between meeting
      the challenges of avoiding overhydration and preventing dehydration. To
      understand how green-backed firecrowns (Sephanoides sephanoides) accomplish this,
      we examined the response of water-handling processes in the gastrointestinal
      tract (GIT) and kidney to different rates of water intake during the evening,
      night, and morning. Fractional water absorption in the GIT was independent of
      water intake rate (evening: 0.91 +/- 0.08; morning: 0.88 +/- 0.04). Consistent
      with this nonregulated water absorption, we found linear increases in water flux,
      fractional turnover of body water, and the rate of renal water loading as water
      intake rate increased during both the evening and morning. Despite these
      relationships, glomerular filtration rate (GFR) was insensitive to water loading
      (evening: 2.08 +/- 0.56 ml/h; morning: 1.84 +/- 0.68 ml/h) and less than the
      allometric expectation (2.92 ml/h). During the evening, fractional renal water
      reabsorption decreased linearly as the rate of water intake increased. At night,
      a period of natural fasting for hummingbirds, mean GFR was not different from
      zero (0.00 +/- 0.05 ml/h). These findings indicate that green-backed firecrowns
      eliminate excess ingested water by decreasing water reabsorption in the kidney;
      to conserve water, it appears that hummingbirds arrest whole kidney GFR,
      effectively preventing urinary water losses. After discounting evaporative water
      losses, our results show that hummingbirds rely principally on their renal system
      to resolve the osmoregulatory quandary posed by nectarivory.

PMID- 16614057
TI  - Glucokinase and hexokinase expression and activities in rainbow trout tissues:
      changes with food deprivation and refeeding.
AB  - The expression and activities of glucokinase (GK) and hexokinase (HK) were
      assessed in different tissues of rainbow trout (Oncorhynchus mykiss) under
      different feeding conditions (fed, fasted for 14 days, and refed for 7 days). Two
      different HK-I cDNAs were identified with different tissue distributions. One
      transcript named heart or H-HK-I was observed in the four brain regions assessed,
      white muscle, kidney, and gills but not in liver or erythrocytes. A second
      transcript named liver or L-HK-I was found in all tissues surveyed. GK mRNA was
      identified only in liver and the four brain regions. GK expression was altered by
      feeding conditions, especially in liver and hypothalamus where food deprivation
      decreased and re-feeding increased expression; changes in expression reflected
      activity changes and changes in tissue glycogen levels. In contrast, feeding
      conditions did not alter expression of either HK-I transcript but did alter
      tissue HK activities. The reduced phosphorylating capacity noted with food
      deprivation correlates primarily with changes in tissue HK, whereas increased
      capacity, as with refeeding, was associated with changes in GK; these changes fit
      with the different K(m) values of the GK and HK enzymes. These results provide
      evidence for the hypothalamus acting as a glucosensor in trout, as hyperglycemia
      produced increased GK expression and activity, as well as increased glycogen
      levels. Thus, even though trout use glucose poorly, none of the parameters tested
      here relate to this inability to use glucose and suggest that, at least, rainbow
      trout, if given an appropriate carbohydrate diet, could metabolically adjust to
      such a diet.

PMID- 16614058
TI  - IGF-1 is downregulated in experimental cancer cachexia.
AB  - Cancer cachexia is characterized by skeletal muscle wasting that is mainly
      supported by hypercatabolism. Muscle atrophy has been suggested to depend on
      impaired IGF-1 signal transduction pathway. The present study has been aimed at
      investigating the IGF-1 system in rats bearing the AH-130 hepatoma, a well
      characterized model of cachexia. IGF-1 mRNA expression in the gastrocnemius of
      tumor hosts progressively decreases to approximately 50% of controls. By
      contrast, both IGF-1 receptor and insulin receptor mRNA levels increase in day 7
      AH-130 hosts. IGF-1 and insulin circulating levels, as well as IGF-1 expression
      in the liver, are reduced. Muscle wasting in the AH-130 bearers is associated
      with hyperactivation of the ubiquitin-proteasome system. Consistently, the mRNA
      levels of ubiquitin and of the ubiquitin ligases atrogin-1 and MuRF1 are
      significantly increased in the gastrocnemius of day 7 AH-130 hosts. Exogenous IGF
      1 administered to tumor bearers does not prevent cachexia. IGF-1 mRNA levels also
      have been evaluated in the gastrocnemius of AH-130 hosts treated with
      pentoxifylline, an inhibitor of TNF-alpha synthesis, alone or combined with
      formoterol, a beta(2)-adrenergic agonist. Both treatments partially correct
      muscle atrophy without modifying IGF-1 and atrogin-1 mRNA levels, whereas MuRF1
      hyperexpression is reduced by the combination of pentoxifylline with formoterol.
      These results demonstrate for the first time that the IGF-1 system is
      downregulated in cancer cachexia, although the underlying mechanism remains
      unknown. Moreover, no simple relation linking IGF-1 and/or atrogin-1 mRNA levels
      and muscle atrophy could be observed in these experimental conditions. Further
      studies are thus needed to clarify both issues.

PMID- 16614059
TI  - Expression of corticotropin-releasing factor and CRF receptors in micturition
      pathways after cyclophosphamide-induced cystitis.
AB  - Corticotropin-releasing factor (CRF) is a prominent neuropeptide involved in
      micturition reflexes, and different roles in these reflexes have been suggested.
      These studies examined the expression of CRF in the urinary bladder and
      lumbosacral sacral parasympathetic nucleus (SPN) in response to cyclophosphamide
      (CYP)-induced cystitis (4 h, 48 h, or chronic) in rats. The expression of CRF
      receptors, CRF(1) and CRF(2), was examined in urinary bladder from control and
      CYP-treated rats. Urinary bladder and lumbosacral spinal cord were harvested from
      rats killed by isoflurane (4%) and thoracotomy. CRF protein expression in whole
      urinary bladders significantly (P < or = 0.01) increased with 48 h or chronic CYP
      treatment. CRF immunoreactivity (IR) was increased significantly (P < or = 0.01)
      in the urothelium and SPN after CYP treatment. CRF IR nerve fibers increased in
      density in the suburothelial plexus and detrusor smooth muscle whole mounts with
      CYP-induced cystitis. CRF(2) receptor transcript was expressed in the urothelium
      or detrusor smooth muscle, and CRF(2) receptor expression increased in whole
      bladder with CYP-treatment, whereas no CRF(1) receptor transcript was expressed
      in either urothelium or detrusor. Immunohistochemical studies demonstrated CRF(2)
      IR in urinary bladder nerve fibers and urothelial cells from control animals,
      whereas no CRF(1) IR was observed. These studies demonstrated changes in the
      expression of CRF in urinary bladder and SPN region with CYP-induced cystitis and
      CRF receptor (CRF(2)) expression in nerve fibers and urothelium in control rats.
      CRF may contribute to urinary bladder overactivity and altered sensory processing
      with CYP-induced cystitis.

PMID- 16614061
TI  - Sex differences in regional brain response to aversive pelvic visceral stimuli.
AB  - To explore sex differences in the response of seven brain regions to an aversive
      pelvic visceral stimulus, functional magnetic resonance images were acquired from
      13 healthy adults (6 women) during 15 s of cued rectal distension at two
      pressures: 25 mmHg (uncomfortable), and 45 mmHg (mild pain), as well as during an
      expectation condition (no distension). Random-effects analyses combining subject
      data voxelwise found 45-mmHg pressure significantly activated the insular and
      anterior cingulate cortices in both sexes. In men only, the left thalamus and
      ventral striatum were also activated. Although all activations appeared more
      extensive in men, no sex difference attained significance. To explore the
      presence of deactivations, which are generally cancelled by more numerous
      activations when subjects are combined for each voxel, the number of activated
      voxels, number of deactivated voxels, and ratio of deactivated voxels to total
      voxels affected were assessed via random-effects, mixed-model analyses combining
      subject data at the region level. Greater insula activation in men compared with
      women was seen during the expectation condition and during the 25-mmHg
      distension. Greater deactivations in women were seen in the amygdala (25-mmHg
      distension) and midcingulate (45-mmHg distension). Women had a significantly
      higher proportion of deactivated voxels than men in all four subcortical
      structures during 25-mmHg distension. Greater familiarity of females with
      physiological pelvic visceral discomfort may have enhanced brain systems that
      dampen arousal networks during lower levels of discomfort.

PMID- 16614060
TI  - Individual differences in physical activity are closely associated with changes
      in body weight in adult female rhesus monkeys (Macaca mulatta).
AB  - The increased prevalence of overweight adults has serious health consequences.
      Epidemiological studies suggest an association between low activity and being
      overweight; however, few studies have objectively measured activity during a
      period of weight gain, so it is unknown whether low activity is a cause or
      consequence of being overweight. To determine whether individual differences in
      adult weight gain are linked to an individual's activity level, we measured
      activity, via accelerometry, over a prolonged period (9 mo) in 18 adult female
      rhesus monkeys. Weight, food intake, metabolic rate, and activity were first
      monitored over a 3-mo period. During this period, there was mild but significant
      weight gain (5.5 +/- 0.88%; t =-6.3, df = 17, P < 0.0001), whereas caloric intake
      and activity remained stable. Metabolic rate increased, as expected, with weight
      gain. Activity level correlated with weight gain (r = -0.52, P = 0.04), and the
      most active monkeys gained less weight than the least active monkeys (t = -2.74,
      df = 8, P = 0.03). Moreover, there was an eightfold difference in activity
      between the most and least active monkeys, and initial activity of each monkey
      was highly correlated with their activity after 9 mo (r = 0.85, P < 0.0001). In
      contrast, food intake did not correlate with weight gain, and there was no
      difference in weight gain between monkeys with the highest vs. lowest caloric
      intake, total metabolic rate, or basal metabolic rate. We conclude that physical
      activity is a particularly important factor contributing to weight change in
      adulthood and that there are large, but stable, differences in physical activity
      among individuals.

PMID- 16614062
TI  - Central angiotensin AT1-receptor blockade affects thermoregulation and running
      performance in rats.
AB  - The effect of central angiotensin AT1-receptor blockade on thermoregulation in
      rats during exercise on a treadmill (18 m/min, 5% inclination) was investigated.
      Core (Tb) and skin tail temperatures were measured in rats while they were
      exercising until fatigue after injection of 2 microl of losartan (Los; 20 nmol, n
      = 4; 30 nmol, n = 4; 60 nmol, n = 7), an angiotensin II AT1-receptor antagonist,
      or 2 microl of 0.15 mol/l NaCl (Sal; n = 15) into the right lateral cerebral
      ventricle. Body heat rate (BHR), heat storage rate, threshold Tb for tail
      vasodilation (TTbV), time to fatigue, and workload were calculated. During
      exercise, the BHR and heat storage rate of Los-treated animals were,
      respectively, 40 and 53% higher (P < 0.01) than in Sal-treated animals.
      Additionally, rats injected with Los showed an increased TTbV (38.59 +/- 0.19
      degrees C for Los vs. 38.12 +/- 0.1 degrees C for Sal, P < 0.02), a higher Tb at
      fatigue point (39.07 +/- 0.14 degrees C Los vs. 38.66 +/- 0.07 degrees C Sal, P <
      0.01), and a reduced running performance (27.29 +/- 4.48 min Los vs. 52.47 +/-
      6.67 min Sal, P < 0.01), which was closely related to the increased BHR. Our data
      suggest that AT1-receptor blockade attenuates heat dissipation during exercise
      due to the higher TTbV, leading to a faster exercise-induced increase in Tb, thus
      decreasing running performance.

PMID- 16614063
TI  - Dynamic responses of the glutathione system to acute oxidative stress in
      dystrophic mouse (mdx) muscles.
AB  - The precise mechanisms underlying skeletal muscle damage in Duchenne muscular
      dystrophy (DMD) remain ill-defined. Functional ischemia during muscle activation,
      with subsequent reperfusion during rest, has been documented. Therefore, one
      possibility is the presence of increased oxidative stress. We applied a model of
      acute hindlimb ischemia/reperfusion (I/R) in mdx mice (genetic homolog of DMD) to
      evaluate dynamic in vivo responses of dystrophic muscles to this form of
      oxidative stress. Before the application of I/R, mdx muscles showed: 1) decreased
      levels of total glutathione (GSH) with an increased oxidized (GSSG)-to-reduced
      (GSH) glutathione ratio; 2) greater activity of the GSH-metabolizing enzymes
      glutathione peroxidase (GPx) and glutathione reductase; and 3) lower activity
      levels of NADP-linked isocitrate dehydrogenase (ICDH) and aconitase, two
      metabolic enzymes that are sensitive to inactivation by oxidative stress and also
      implicated in GSH regeneration. Interestingly, nondystrophic muscles subjected to
      I/R exhibited similar changes in total glutathione, GSSG/GSH, GPx, ICDH, and
      aconitase. In contrast, all of the above remained stable in mdx muscles subjected
      to I/R. Taken together, these results suggest that mdx muscles are chronically
      subjected to increased oxidative stress, leading to adaptive changes that attempt
      to protect (although only in part) the dystrophic muscles from acute I/R-induced
      oxidative stress. In addition, mdx muscles show significant impairment of the
      redox-sensitive metabolic enzymes ICDH and aconitase, which may further
      contribute to contractile dysfunction in dystrophic muscles.

PMID- 16614064
TI  - In vivo oxidative metabolism of a major peroxidation-derived DNA adduct, M1dG.
AB  - 3-(2-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one
      (M1dG) is a DNA adduct arising from the reaction of 2-deoxyguanosine with the
      lipid peroxidation product, malondialdehyde, or the DNA peroxidation product,
      base propenal. M1dG is mutagenic in bacteria and mammalian cells and is present
      in the genomic DNA of healthy human beings. It is also detectable, albeit at low
      levels, in the urine of healthy individuals, which may make it a useful biomarker
      of DNA damage linked to oxidative stress. We investigated the possibility that
      the low urinary levels of M1dG reflect metabolic conversion to derivatives. M1dG
      was rapidly removed from plasma (t(1/2) = 10 min) after i.v. administration to
      rats. A single urinary metabolite was detected that was identified as 6-oxo-M1dG
      by MS, NMR spectroscopy, and independent chemical synthesis. 6-Oxo-M1dG was
      generated in vitro by incubation of M1dG with rat liver cytosols, and studies
      with inhibitors suggested that xanthine oxidase and aldehyde oxidase are involved
      in the oxidative metabolism. M1dG also was metabolized by three separate human
      liver cytosol preparations, indicating 6-oxo-M1dG is a likely metabolite in
      humans. This represents a report of the oxidative metabolism of an endogenous DNA
      adduct and raises the possibility that other endogenous DNA adducts are
      metabolized by oxidative pathways. 6-Oxo-M1dG may be a useful biomarker of
      endogenous DNA damage associated with inflammation, oxidative stress, and certain
      types of cancer chemotherapy.

PMID- 16614065
TI  - A collagenous protective coat enables Metarhizium anisopliae to evade insect
      immune responses.
AB  - The ubiquitous fungal pathogen Metarhizium anisopliae kills a wide range of
      insects. Host hemocytes can recognize and ingest its conidia, but this capacity
      is lost on production of hyphal bodies. We show that the unusual ability of
      hyphal bodies to avoid detection depends on a gene (Mcl1) that is expressed
      within 20 min of the pathogen contacting hemolymph. A mutant disrupted in Mcl1 is
      rapidly attacked by hemocytes and shows a corresponding reduction of virulence to
      Manduca sexta. Mcl1 encodes a three domain protein comprising a hydrophilic,
      negatively charged N-terminal region with 14 cysteine residues, a central region
      comprising tandem repeats (GXY) characteristic of collagenous domains, and a C
      terminal region that includes a glycosylphosphatidylinositol-dependent cell wall
      attachment site. Immunofluorescence assay showed that hyphal bodies are covered
      by the N-terminal domains of MCL1. The collagen domain became antibody accessible
      after treatment with DTT, suggesting that the N termini are linked by interchain
      disulfide bonds and are presented on the cell surface by extended collagenous
      fibers. Studies with staining reagents and hemocyte monolayers showed that MCL1
      functions as an antiadhesive protective coat because it masks antigenic
      structural components of the cell wall such as beta-glucans, and because its
      hydrophilic negatively charged nature makes it unattractive to hemocytes. A
      survey of 54 fungal genomes revealed that seven other species have proteins with
      collagenous domains suggesting that MCL1 is a member of a patchily distributed
      gene family.

PMID- 16614066
TI  - Direct electrical detection of DNA synthesis.
AB  - Rapid, sequence-specific DNA detection is essential for applications in medical
      diagnostics and genetic screening. Electrical biosensors that use immobilized
      nucleic acids are especially promising in these applications because of their
      potential for miniaturization and automation. Current DNA detection methods based
      on sequencing by synthesis rely on optical readouts; however, a direct electrical
      detection method for this technique is not available. We report here an approach
      for direct electrical detection of enzymatically catalyzed DNA synthesis by
      induced surface charge perturbation. We discovered that incorporation of a
      complementary deoxynucleotide (dNTP) into a self-primed single-stranded DNA
      attached to the surface of a gold electrode evokes an electrode surface charge
      perturbation. This event can be detected as a transient current by a voltage
      clamp amplifier. Based on current understanding of polarizable interfaces, we
      propose that the electrode detects proton removal from the 3'-hydroxyl group of
      the DNA molecule during phosphodiester bond formation.

PMID- 16614067
TI  - Vailulu'u Seamount, Samoa: Life and death on an active submarine volcano.
AB  - Submersible exploration of the Samoan hotspot revealed a new, 300-m-tall,
      volcanic cone, named Nafanua, in the summit crater of Vailulu'u seamount. Nafanua
      grew from the 1,000-m-deep crater floor in <4 years and could reach the sea
      surface within decades. Vents fill Vailulu'u crater with a thick suspension of
      particulates and apparently toxic fluids that mix with seawater entering from the
      crater breaches. Low-temperature vents form Fe oxide chimneys in many locations
      and up to 1-m-thick layers of hydrothermal Fe floc on Nafanua. High-temperature
      (81 degrees C) hydrothermal vents in the northern moat (945-m water depth)
      produce acidic fluids (pH 2.7) with rising droplets of (probably) liquid CO(2).
      The Nafanua summit vent area is inhabited by a thriving population of eels
      (Dysommina rugosa) that feed on midwater shrimp probably concentrated by
      anticyclonic currents at the volcano summit and rim. The moat and crater floor
      around the new volcano are littered with dead metazoans that apparently died from
      exposure to hydrothermal emissions. Acid-tolerant polychaetes (Polynoidae) live
      in this environment, apparently feeding on bacteria from decaying fish carcasses.
      Vailulu'u is an unpredictable and very active underwater volcano presenting a
      potential long-term volcanic hazard. Although eels thrive in hydrothermal vents
      at the summit of Nafanua, venting elsewhere in the crater causes mass mortality.
      Paradoxically, the same anticyclonic currents that deliver food to the eels may
      also concentrate a wide variety of nektonic animals in a death trap of toxic
      hydrothermal fluids.

PMID- 16614068
TI  - Limited evolutionary conservation of imprinting in the human placenta.
AB  - The epigenetic phenomenon of genomic imprinting provides an additional level of
      gene regulation that is confined to a limited number of genes, frequently, but
      not exclusively, important for embryonic development. The evolution and
      maintenance of imprinting has been linked to the balance between the allocation
      of maternal resources to the developing fetus and the mother's well being. Genes
      that are imprinted in both the embryo and extraembryonic tissues show extensive
      conservation between a mouse and a human. Here we examine the human orthologues
      of mouse genes imprinted only in the placenta, assaying allele-specific
      expression and epigenetic modifications. The genes from the KCNQ1 domain and the
      isolated human orthologues of the imprinted genes Gatm and Dcn all are expressed
      biallelically in the human, from first-trimester trophoblast through to term.
      This lack of imprinting is independent of promoter CpG methylation and correlates
      with the absence of the allelic histone modifications dimethylation of lysine-9
      residue of H3 (H3K9me2) and trimethylation of lysine-27 residue of H3 (H3K27me3).
      These specific histone modifications are thought to contribute toward regulation
      of imprinting in the mouse. Genes from the IGF2R domain show polymorphic
      concordant expression in the placenta, with imprinting demonstrated in only a
      minority of samples. Together these findings have important implications for
      understanding the evolution of mammalian genomic imprinting. Because most human
      pregnancies are singletons, this absence of competition might explain the
      comparatively relaxed need in the human for placental-specific imprinting.

PMID- 16614069
TI  - Monte Carlo simulations of proton pumps: on the working principles of the
      biological valve that controls proton pumping in cytochrome c oxidase.
AB  - Gaining a detailed understanding of the proton-pumping process in cytochrome c
      oxidase (COX) is one of the challenges of modern biophysics. Recent mutation
      experiments have highlighted this challenge by showing that a single mutation
      (the N139D mutation) blocks the overall pumping while continuing to channel
      protons to the binuclear center without inhibiting the oxidase activity.
      Rationalizing this result has been a major problem because the mutation is quite
      far from E286, which is believed to serve as the branching point for the proton
      transport in the pumping process. In the absence of a reasonable explanation for
      this important observation, we have developed a Monte Carlo simulation method
      that can convert mutation and structural information to pathways for proton
      translocation and simulate the pumping process in COX on a millisecond and even
      subsecond time scale. This tool allows us to reproduce and propose a possible
      explanation to the effect of the N139D mutation and to offer a consistent model
      for the origin of the "valve effect" in COX, which is crucial for maintaining
      uphill proton pumping. Furthermore, obtaining the first structure-based
      simulation of proton pumping in COX, or in any other protein, indicates that our
      approach should provide a powerful tool for verification of mechanistic
      hypotheses about the action of proton transport proteins.

PMID- 16614070
TI  - Quantifying archaeal community autotrophy in the mesopelagic ocean using natural
      radiocarbon.
AB  - An ammonia-oxidizing, carbon-fixing archaeon, Candidatus "Nitrosopumilus
      maritimus," recently was isolated from a salt-water aquarium, definitively
      confirming that chemoautotrophy exists among the marine archaea. However, in
      other incubation studies, pelagic archaea also were capable of using organic
      carbon. It has remained unknown what fraction of the total marine archaeal
      community is autotrophic in situ. If archaea live primarily as autotrophs in the
      natural environment, a large ammonia-oxidizing population would play a
      significant role in marine nitrification. Here we use the natural distribution of
      radiocarbon in archaeal membrane lipids to quantify the bulk carbon metabolism of
      archaea at two depths in the subtropical North Pacific gyre. Our compound
      specific radiocarbon data show that the archaea in surface waters incorporate
      modern carbon into their membrane lipids, and archaea at 670 m incorporate carbon
      that is slightly more isotopically enriched than inorganic carbon at the same
      depth. An isotopic mass balance model shows that the dominant metabolism at depth
      indeed is autotrophy (83%), whereas heterotrophic consumption of modern organic
      carbon accounts for the remainder of archaeal biomass. These results reflect the
      in situ production of the total community that produces tetraether lipids and are
      not subject to biases associated with incubation and/or culture experiments. The
      data suggest either that the marine archaeal community includes both autotrophs
      and heterotrophs or is a single population with a uniformly mixotrophic
      metabolism. The metabolic and phylogenetic diversity of the marine archaea
      warrants further exploration; these organisms may play a major role in the marine
      cycles of nitrogen and carbon.

PMID- 16614071
TI  - S-adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox
      capacity.
AB  - The transsulfuration pathway converts homocysteine to cysteine and represents the
      metabolic link between antioxidant and methylation metabolism. The first and
      committing step in this pathway is catalyzed by cystathionine beta-synthase
      (CBS), which is subject to complex regulation, including allosteric activation by
      the methyl donor, S-adenosylmethionine (AdoMet). In this study, we demonstrate
      that methionine restriction leads to a >10-fold decrease in CBS protein levels,
      and pulse proteolysis studies reveal that binding of AdoMet stabilizes the
      protein against degradation by approximately 12 kcal/mol. These observations
      predict that under pathological conditions where AdoMet levels are diminished,
      CBS, and therefore glutathione levels, will be reduced. Indeed, we demonstrate
      this to be the case in a mouse model for spontaneous steatohepatitis in which the
      gene for the MAT1A isoenzyme encoding AdoMet synthetase has been disrupted, and
      in human hepatocellular carcinoma, where MAT1A is silenced. Furthermore,
      diminished CBS levels are associated with reduced cell viability in hepatoma
      cells challenged with tert-butyl hydroperoxide. This study uncovers a mechanism
      by which CBS is allosterically activated by AdoMet under normal conditions but is
      destabilized under pathological conditions, for redirecting the metabolic flux
      toward methionine conservation. A mechanistic basis for the coordinate changes in
      redox and methylation metabolism that are a hallmark of several complex diseases
      is explained by these observations.

PMID- 16614072
TI  - Element interactions limit soil carbon storage.
AB  - Rising levels of atmospheric CO2 are thought to increase C sinks in terrestrial
      ecosystems. The potential of these sinks to mitigate CO2 emissions, however, may
      be constrained by nutrients. By using metaanalysis, we found that elevated CO2
      only causes accumulation of soil C when N is added at rates well above typical
      atmospheric N inputs. Similarly, elevated CO2 only enhances N2 fixation, the
      major natural process providing soil N input, when other nutrients (e.g.,
      phosphorus, molybdenum, and potassium) are added. Hence, soil C sequestration
      under elevated CO2 is constrained both directly by N availability and indirectly
      by nutrients needed to support N2 fixation.

PMID- 16614073
TI  - Defocused orientation and position imaging (DOPI) of myosin V.
AB  - The centroid of a fluorophore can be determined within approximately 1.5-nm
      accuracy from its focused image through fluorescence imaging with one-nanometer
      accuracy (FIONA). If, instead, the sample is moved away from the focus, the point
      spread-function depends on both the position and 3D orientation of the
      fluorophore, which can be calculated by defocused orientation and position
      imaging (DOPI). DOPI does not always yield position accurately, but it is
      possible to switch back and forth between focused and defocused imaging, thereby
      getting the centroid and the orientation with precision. We have measured the 3D
      orientation and stepping behavior of single bifunctional rhodamine probes
      attached to one of the calmodulins of the light-chain domain (LCD) of myosin V as
      myosin V moves along actin. Concomitant with large and small steps, the LCD
      rotates and then dwells in the leading and trailing position, respectively. The
      probe angle relative to the barbed end of the actin (beta) averaged 128 degrees
      while the LCD was in the leading state and 57 degrees in the trailing state. The
      angular difference of 71 degrees represents rotation of LCD around the bound
      motor domain and is consistent with a 37-nm forward step size of myosin V. When
      beta changes, the probe rotates +/-27 degrees azimuthally around actin and then
      rotates back again on the next step. Our results remove degeneracy in angles and
      the appearance of nontilting lever arms that were reported.

PMID- 16614075
TI  - Cart overexpression is the only identifiable cause of high bone mass in
      melanocortin 4 receptor deficiency.
AB  - The neural regulation of bone remodeling has proven to be increasingly complex at
      the molecular level because it involves both positive and negative mediators of
      bone formation and resorption. One of the mediators expressed in hypothalamic
      neurons that leptin uses to inhibit osteoclast differentiation and thereby bone
      resorption is cocaine- and amphetamine-regulated transcript (CART). CART
      expression in the hypothalamus is increased in mice lacking melanocortin 4
      receptor (Mc4r(-/-) mice). Moreover, we show here that humans or mice lacking
      only one allele of Mc4r display a decrease in bone resorption parameters, high
      bone mass, and an increase in CART serum levels and/or hypothalamic expression.
      To demonstrate that the Cart overexpression is the only identifiable cause for
      the high bone mass observed upon Mc4r inactivation, we removed one allele of Cart
      from mice either heterozygous or homozygous for Mc4r inactivation. This
      manipulation sufficed to either significantly improve or normalize bone
      resorption parameters, without improving the energy metabolism disturbance that
      characterizes Mc4r-deficient mice. These results identify CART signaling as the
      main if not only molecular pathway accounting for the decrease in bone resorption
      leading to high bone mass in mice and humans deficient in Mc4r. As importantly,
      they also indicate that CART regulates bone resorption independently of the role
      it may exert in energy metabolism, suggesting that the neural control of appetite
      and bone remodeling are independent of each other.

PMID- 16614074
TI  - Lack of IL-15 results in the suboptimal priming of CD4+ T cell response against
      an intracellular parasite.
AB  - IFN-gamma-producing CD4+ T cells, although important for protection against acute
      Toxoplasma gondii infection, can cause gut pathology, which may prove to be
      detrimental for host survival. Here we show that mice lacking IL-15 gene develop
      a down-regulated IFN-gamma-producing CD4+ T cell response against the parasite,
      which leads to a reduction in gut necrosis and increased level of survival
      against infection. Moreover, transfer of immune CD4+ T cells from WT to IL-15-/-
      mice reversed inhibition of gut pathology and caused mortality equivalent to
      levels of parental WT mice. Down-regulated CD4+ T cell response in the absence of
      IL-15, manifested as reduced antigen-specific proliferation, was due to defective
      priming of the T cell subset by dendritic cells (DCs) of these animals. When
      stimulated with antigen-pulsed DCs from WT mice, CD4+ T cells from IL-15-/- mice
      were primed optimally, and robust proliferation of these cells was observed. A
      defect in the DCs of knockout mice was further confirmed by their reduced ability
      to produce IL-12 upon stimulation with Toxoplasma lysate antigen. Addition of
      exogenous IL-15 to DC cultures from knockout mice led to increased IL-12
      production by these cells and restored their ability to prime an optimal parasite
      specific CD4+ T cell response. To our knowledge, this is the first demonstration
      of the role of IL-15 in the development of CD4+ T cell immunity against an
      intracellular pathogen. Furthermore, based on these observations, targeting of IL
      15 should have a beneficial effect on individuals suffering from CD4+ T cell
      mediated autoimmune diseases.

PMID- 16614076
TI  - Differential responsiveness of dopamine-beta-hydroxylase gene expression to
      glucoprivation in different catecholamine cell groups.
AB  - Hindbrain catecholaminergic neurons are key participants in systemic
      glucoregulation. However, the specific subpopulations critical for
      glucoregulatory function have not been fully identified. Here we used in situ
      hybridization and immunohistochemistry to investigate effects of glucoprivation
      on expression of the gene for the catecholamine biosynthetic enzyme, dopamine
      beta-hydroxylase (DBH), to further localize the critical cell populations.
      Glucoprivation induced by the glycolytic inhibitor, 2-deoxy-D-glucose (2DG) (250
      mg/kg) increased total DBH mRNA expression in caudal ventrolateral medullary cell
      groups (namely A1, the A1/C1 overlap, and the middle portion of C1) from six to
      49 times control levels. In retrofacial C1, no enhancement was observed. In the
      dorsomedial medulla, hybridization signal was modestly increased (tripled) in A2
      but was not increased in the area postrema. Previous microinjection of the
      retrogradely transported catecholamine immunotoxin (anti-DBH-saporin, or DSAP)
      into the paraventricular nucleus of the hypothalamus reduced the number of DBH
      immunoreactive cells in cell groups known to project to the paraventricular
      nucleus of the hypothalamus as well as reducing the 2DG-stimulated increases in
      total DBH mRNA expression in the caudal ventrolateral medulla and A2. The strong
      enhancement of DBH gene expression by glucoprivation is consistent with the
      demonstrated importance of catecholaminergic neurons for glucoregulation. The
      differential sensitivity of these neurons to glucoprivation is evidence of
      functional specialization within the total population. The pattern of 2DG-induced
      gene expression indicates that the ventrolateral medulla contains the vast
      majority of catecholamine neurons responsive to glucoprivation.

PMID- 16614077
TI  - Glucocorticoid regulation of osteoclast differentiation and expression of
      receptor activator of nuclear factor-kappaB (NF-kappaB) ligand, osteoprotegerin,
      and receptor activator of NF-kappaB in mouse calvarial bones.
AB  - In the present study, dexamethasone treatment of neonatal mouse calvarial bones
      increased mRNA expression of tartrate-resistant acid phosphatase, calcitonin
      receptor (CTR), cathepsin K, carbonic anhydrase II, osteoprotegerin (OPG), and
      receptor activator of nuclear factor-kappaB (RANK) as well as mRNA and protein
      expression of RANK ligand (RANKL). The increase in OPG mRNA noted with
      dexamethasone was in contrast to 1,25(OH)(2)-vitamin D3 (D3) treatment, which
      decreased OPG expression. Stimulation of (45)Ca release by dexamethasone and
      hydrocortisone in calvariae was blocked by OPG. Stimulation of RANKL, RANK, OPG,
      and CTR mRNA expression by dexamethasone in calvariae was blocked by the
      glucocorticoid receptor antagonist RU 38,486. Greater than additive potentiations
      of CTR mRNA and RANKL mRNA and protein were observed when D3 and dexamethasone
      were combined. Vitamin D receptor mRNA was increased by dexamethasone and D3,
      whereas glucocorticoid receptor (GR) mRNA was decreased by dexamethasone and
      unaffected by D3. No synergistic interaction between dexamethasone and D3 on
      either vitamin D receptor or GR mRNA expression was noted. The data demonstrate
      that dexamethasone-induced bone resorption in calvarial bones is associated with
      increased differentiation of osteoclasts and regulation of the RANKL-RANK-OPG
      system. The increase in OPG expression and the decrease of GR expression noted
      with dexamethasone offer an explanation for why bone breakdown in mouse calvariae
      treated with glucocorticoids is less than that caused by resorptive agents like
      D3. The synergistic stimulation of RANKL by dexamethasone and D3 offers an
      explanation of how glucocorticoids and D3 interact to potentiate bone resorption.

PMID- 16614078
TI  - Contribution of multidrug resistance protein MRP5 in control of cyclic guanosine
      5'-monophosphate intracellular signaling in anterior pituitary cells.
AB  - The energy-dependent cyclic nucleotide cellular efflux is operative in numerous
      eukaryotic cells and could be mediated by multidrug resistance proteins MRP4,
      MRP5, and MRP8. In pituitary cells, however, the operation of export pumps and
      their contribution to the control of intracellular cyclic nucleotide levels were
      not studied previously. Here we show that cellular efflux of cyclic nucleotides
      was detectable in normal and immortalized GH(3) pituitary cells under resting
      conditions and was enlarged after concurrent stimulation of cAMP and cGMP
      production with GHRH, corticotropin-releasing factor, vasoactive intestinal
      peptide, pituitary adenylate cyclase-activating polypeptide, and forskolin. In
      resting and stimulated cells, the efflux pumps transported the majority of de
      novo-produced cGMP, limiting its intracellular accumulation in a concentration
      range of 1-2 microm. In contrast, only a small fraction of cAMP was released and
      there was a time- and concentration-dependent accumulation of this messenger in
      the cytosol, ranging from 1-100 microm. Stimulation and inhibition of cGMP
      production alone did not affect cAMP efflux, suggesting the operation of two
      different transport pathways in pituitary cells. The rates of cAMP and cGMP
      effluxes were comparable, and both pathways were blocked by probenecid and
      progesterone. Pituitary cells expressed mRNA transcripts for MRP4, MRP5, and
      MRP8, whereas GH(3) cells expressed only transcripts for MRP5. Down-regulation of
      MRP5 expression in GH(3) cells decreased cGMP release without affecting cAMP
      efflux. These results indicate that cyclic nucleotide cellular efflux plays a
      critical role in elimination of intracellular cGMP but not cAMP in pituitary
      cells and that such selectivity is achieved by expression of MRP5.

PMID- 16614079
TI  - Insulin-like growth factor binding protein 3 has opposing actions on malignant
      and nonmalignant breast epithelial cells that are each reversible and dependent
      upon cholesterol-stabilized integrin receptor complexes.
AB  - IGF-binding protein (IGFBP)-3 is generally considered to have actions that
      counterbalance those of IGFs and is therefore being developed as a cancer
      treatment. In breast tumors, however, high levels are associated with aggressive
      tumors and poor prognosis. Consistent with this we have demonstrated that
      although IGFBP-3 and a non-IGF-binding fragment (serine phosphorylation domain
      peptide) reduced attachment and enhanced apoptosis of Hs578T breast cancer cells
      cultured on collagen or laminin, it promoted their attachment and survival on
      fibronectin, which is abundant in the matrix of aggressive tumors. We have now
      examined the factors that determine whether IGFBP-3 has positive or negative
      actions on breast epithelial cells. IGFBP-3 also promoted survival of Hs578T
      cells in the presence of an antibody to the beta1-integrin subunit or when
      cholesterol-stabilized complexes were disrupted. These actions were blocked by
      IGF-I or a MAPK inhibitor. Serine phosphorylation domain peptide had similar
      actions on MCF-7 cells that were again reversed on fibronectin or with disruption
      of cholesterol-stabilized complexes and blocked by the beta1-integrin antibody.
      In contrast, IGFBP-3 promoted growth and survival for nonmalignant MCF-10A cells,
      but these effects were again reversed on fibronectin and blocked by the beta1
      antibody or a MAPK inhibitor or by disruption of cholesterol-stabilized
      complexes. On Hs578T cells, IGFBP-3 bound to caveolin-1 and beta1-integrins,
      enhancing their aggregation, the recruitment of focal adhesion kinase, and the
      activation of MAPK. In summary, with three breast epithelial cell lines, IGFBP-3
      had positive or negative effects on growth and survival dependent upon the status
      of cholesterol-stabilized integrin receptor complexes.

PMID- 16614080
TI  - Sterol regulatory element binding protein-1a transactivates 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase gene promoter.
AB  - 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) catalyzes the
      synthesis and degradation of fructose-2,6-bisphosphate, a key modulator of
      glycolysis-gluconeogenesis. To gain insight into the molecular mechanism behind
      hormonal and nutritional regulation of PFKFB expression, we have cloned and
      characterized the proximal promoter region of the liver isoform of PFKFB (PFKFB1)
      from gilthead sea bream (Sparus aurata). Transient transfection of HepG2 cells
      with deleted gene promoter constructs and electrophoretic mobility shift assays
      allowed us to identify a sterol regulatory element (SRE) to which SRE binding
      protein-1a (SREBP-1a) binds and transactivates PFKFB1 gene transcription.
      Mutating the SRE box abolished SREBP-1a binding and transactivation. The in vivo
      binding of SREBP-1a to the SRE box in the S. aurata PFKFB1 promoter was confirmed
      by chromatin immunoprecipitation assays. There is a great deal of evidence for a
      postprandial rise of PFKB1 mRNA levels in fish and rats. Consistently, starved-to
      fed transition and treatment with glucose or insulin increased SREBP-1
      immunodetectable levels, SREBP-1 association to PFKFB1 promoter, and PFKFB1 mRNA
      levels in the piscine liver. Our findings demonstrate involvement of SREBP-1a in
      the transcriptional activation of PFKFB1, and we conclude that SREBP-1a may exert
      a key role mediating postprandial activation of PFKFB1 transcription.

PMID- 16614081
TI  - Activation of the lutropin/choriogonadotropin receptor in MA-10 cells stimulates
      tyrosine kinase cascades that activate ras and the extracellular signal regulated
      kinases (ERK1/2).
AB  - We show that activation of the recombinant lutropin/choriogonadotropin receptor
      (LHR) in mouse Leydig tumor cells (MA-10 cells) leads to the tyrosine
      phosphorylation of Shc (Src homology and collagen homology) and the formation of
      complexes containing Shc and Sos (Son of sevenless), a guanine nucleotide
      exchange factor for Ras. Because a dominant-negative mutant of Shc inhibits the
      LHR-mediated activation of Ras and the phosphorylation of ERK1/2, we conclude
      that the LHR-mediated phosphorylation of ERK1/2 is mediated, at least partially,
      by the classical pathway used by growth factor receptors. We also show that the
      endogenous epidermal growth factor receptor (EGFR) present in MA-10 cells is
      phosphorylated upon activation of the LHR. The LHR-mediated phosphorylation of
      the EGFR and Shc, the activation of Ras, and the phosphorylation of ERK1/2 are
      inhibited by expression of a dominant-negative mutant of Fyn, a member of the Src
      family kinases (SFKs) expressed in MA-10 cells and by PP2, a pharmacological
      inhibitor of the SFKs. These are also inhibited, but to a lesser extent, by
      AG1478, an inhibitor of the EGFR kinase. We conclude that the SFKs are
      responsible for the LHR-mediated phosphorylation of the EGFR and Shc, the
      formation of complexes containing Shc and Sos, the activation of Ras, and the
      phosphorylation of ERK1/2.

PMID- 16614082
TI  - Glucose induces glucagon release pulses antisynchronous with insulin and
      sensitive to purinoceptor inhibition.
AB  - Both increase of the glucose concentration and activation of purinoceptors are
      known to affect pancreatic alpha-cells. Effects obtained with various purino
      derivatives at 2.8 and 8.3 mmol/liter glucose have been taken to indicate that
      external ATP is less potent than adenosine as a stimulator of glucagon release.
      However, when making a corresponding comparison at 20 mmol/liter glucose, we
      observed marked stimulation of glucagon release from isolated rat islets with 100
      micromol/liter adenosine-5-O-2-thiodiphosphate but inhibition with 10
      micromol/liter adenosine. Analyses of 30-sec samples of perfusate from rat
      pancreas indicated that a rise of the glucose concentration from 3 to 20
      mmol/liter rapidly induces a glucagon peak followed by regular 4- to 5-min
      pulses. The glucagon pulses preceded those of insulin with a phase shift (1.8 +/-
      0.1 min) near half the interpeak interval. Because of the antisynchrony, the
      maximal glucagon effect on liver cells will be manifested during periods with low
      concentrations of insulin. In support for the idea that neural P2Y(1) receptors
      are important for coordinating the secretory activity of the islets, both the
      insulin and glucagon pulses disappeared in the presence of the purinoceptor
      inhibitor MRS 2179 (10 micromol/liter). However, in contrast to what was observed
      for insulin, MRS 2179 lowered average glucagon release to the level of the
      oscillatory nadirs.

PMID- 16614083
TI  - Intensity of transmitted photon spectra as a function of transverse and
      longitudinal dimensions of soil medium using 137Cs.
AB  - Transmitted photon spectra (pulse-height distribution) of (137)Cs gamma rays are
      measured through longitudinal and transverse dimensions of the soil medium. The
      intensity (photon fluence rate) of the multiple-scattered peak, appearing in the
      lower energy part of the spectrum, has been studied as a function of longitudinal
      as well as transverse thickness of the soil medium. The intensity of multiple
      scatter peak decreases exponentially with the increase in longitudinal thickness
      of the soil medium, whereas a reverse trend of multiple-scatter peak intensity
      with transverse thickness occurs as the longitudinal dimension increases. The
      soil medium as a whole takes part in multiple scattering affecting the
      intensities of transmitted photons.

PMID- 16614084
TI  - Interstitial brachytherapy dosimetry update.
AB  - In March 2004, the American Association of Physicists in Medicine (AAPM)
      published an update to the AAPM Task Group No. 43 Report (TG-43) which was
      initially published in 1995. This update was pursued primarily due to the marked
      increase in permanent implantation of low-energy photon-emitting brachytherapy
      sources in the United States over the past decade, and clinical rationale for the
      need of accurate dosimetry in the implementation of interstitial brachytherapy.
      Additionally, there were substantial improvements in the brachytherapy dosimetry
      formalism, accuracy of related parameters and methods for determining these
      parameters. With salient background, these improvements are discussed in the
      context of radiation dosimetry. As an example, the impact of this update on the
      administered dose is assessed for the model 200 (103)Pd brachytherapy source.

PMID- 16614086
TI  - LET dependence of bubble detector response to heavy ions.
AB  - A series of experiments have been recently performed at the Heavy Ion Medical
      Accelerator in Chiba (HIMAC) laboratory to study the response of bubble detectors
      to high-mass high-energy (HZE) particles. The motivation for this study was to
      improve our ability to interpret measurements of neutron energy spectra in space.
      A recent analysis showed that emulsions of light halocarbons display common
      properties when they are characterised by a quantity called 'reduced superheat'.
      This quantity evolved from the examination of neutron and gamma responses of many
      types of detectors. In this study, we describe direct irradiations with N, Ar and
      Kr charged particles at HIMAC. It was observed that when the linear energy
      transfer (LET) corresponding to bubble formation was plotted vs. reduced
      superheat, different curves were obtained for a particular ion for detectors at
      different temperatures. Different curves were also obtained when data from
      different ions were plotted. These results confirm that bubble nucleation is not
      a simple function of particle LET and that an analysis based on track-structure
      appears warranted.

PMID- 16614085
TI  - Optical imaging of dose distributions in Fricke gels.
AB  - Ferrous-sulphate infused gels, or 'Fricke gels', encounter great interest in the
      field of radiation dosimetry, due to their potential for 3D radiation dose
      mapping. Typically, magnetic resonance (MR) relaxation rates are determined in
      these systems in order to derive the absorbed dose. However, when large
      concentration gradients are present, diffusion effects before and during the MR
      imaging may not be negligible. In these cases, optical techniques may represent a
      viable alternative. This paper describes research aimed at measuring 3D dose
      distributions in a Fricke-xylenol orange gel by measuring optical density with a
      CCD camera. This method is inexpensive and fast. A series of early experiments is
      described, in which optical density profiles were measured with a commercial
      microdensitometer for film dosimetry. The light box of the device was modified to
      work at 567 nm, close to the maximum absorbance of the ferric ion-xylenol orange
      complex. Under these conditions, the gel shows linearity with dose and high
      sensitivity.

PMID- 16614087
TI  - Dose distribution around a needle-like anode X-ray tube: dye-film vs. planar
      thermoluminescent detectors.
AB  - The dosimetry around the X-ray tube with a needle-like anode (NAXT), developed at
      the Institute of Nuclear Studies, for interstitial brachytherapy has been
      performed using (1) dye films (Gafchromic XR-T), (2) large-area thermoluminescent
      (TL) detectors--prepared either by gluing TL powder onto thin Al foil (so-called
      planar detectors with spatial resolution of 0.1 mm) and (3) miniature (2 mm
      diameter and 0.5 mm thick) TL detectors. The measurements were performed in
      following geometries. (1) Needle inside a PMMA cylinder--the planar TL detector
      mounted on the surface of the cylinder. (2) Needle inside a thick block of PMMA
      and TL detector mounted vertically 7 mm from needle axis. TL detectors were read
      with the planar (2D) thermoluminescence reader, developed at IFJ, with a
      sensitive CCD (charge couple device) camera. Gafchromic films were evaluated with
      a system based on Agfa Arcus 1200 scanner and calibrated with X rays (35 kV)
      filtered with 0.03 mm Mo and with Co-60 photons. The intensity distribution of TL
      light on the planar detector was calibrated in terms of absorbed dose to water,
      using (137)Cs gamma-rays. TL planar detectors seem to be a promising tool for 2D
      dosimetry of miniature X-ray sources. Obtained results for TLDs and Gafchromic
      films seem to be comparable but differences have been found. Both methods are
      useful for measurements of dose distribution around the NAXT X-rays source.

PMID- 16614088
TI  - Analysis of spectrally resolved thermoluminescence of LiF:Mg,Cu,P detectors by
      the surface fitting method using algorithm for unrestricted peak positions.
AB  - Recently developed surface fitting technique is a natural replacement for the
      widely used glow curve deconvolution (GCD) technique. Surface fitting can be
      applied for advanced spectrally resolved thermoluminescence (TL) measurements. It
      combines both kinetic and emission-band analysis. Owing to greater number of
      parameters and data points the algorithm is more time-consuming than usual GCD.
      However, it offers greater reliability in determination of trap parameters. This
      is especially important for spectrally resolved measurements that are usually
      performed at low-light level conditions. This paper demonstrates an application
      of the surface fitting method to the analysis of TL-3D data from LiF:Mg,Cu,P
      detectors. The spectra were analysed using two different variants of surface
      fitting--for restricted and unrestricted peak positions.

PMID- 16614089
TI  - Two-dimensional thermoluminescence dosimetry using planar detectors and a TL
      reader with CCD camera readout.
AB  - A novel method of determining two-dimensional (2-D) dose distributions is
      presented, using in-house developed, large-area (a few cm(2)) thermoluminescent
      (TL) detectors based on LiF powder plated on Al foil. An in-house developed
      planar large-area TL reader equipped with a coupled charge device (CCD) camera is
      used for readout, providing digital images of 2-D dose distributions on the
      surface of these large-area TL detectors. The capability of the newly developed
      system is demonstrated by mapping 2-D dose distributions around a brachytherapy
      source, at dose ranges and source geometries relevant for clinical radiotherapy.
      Examples of local and dynamic evaluation of TL output from conventional TL
      detectors are also shown.

PMID- 16614090
TI  - Tissue-equivalent TL sheet dosimetry system for X- and gamma-ray dose mapping.
AB  - To measure dose distribution for X- and gamma rays simply and accurately, a
      tissue-equivalent thermoluminescent (TL) sheet-type dosemeter and reader system
      were developed. The TL sheet is composed of LiF:Mg,Cu,P and ETFE polymer, and the
      thickness is 0.2 mm. For the TL reading, a square heating plate, 20 cm on each
      side, was developed, and the temperature distribution was measured with an
      infrared thermal imaging camera. As a result, linearity within 2% and the
      homogeneity within 3% were confirmed. The TL signal emitted is detected using a
      CCD camera and displayed as a spatial dose distribution. Irradiation using
      synchrotron radiation between 10 and 100 keV and (60)Co gamma rays showed that
      the TL sheet dosimetry system was promising for radiation dose mapping for
      various purposes.

PMID- 16614091
TI  - Discrimination of photon from proton irradiation using glow curve feature
      extraction and vector analysis.
AB  - Two types of thermoluminescence dosemeters (TLDs), the Harshaw LiF:Mg,Ti (TLD
      100) and CaF(2):Tm (TLD-300) were investigated for their glow curve response to
      separate photon and proton irradiations. The TLDs were exposed to gamma
      irradiation from a (137)Cs source and proton irradiation using a positive ion
      accelerator. The glow curve peak structure for each individual TLD exposure was
      deconvolved to obtain peak height, width, and position. Simulated mixed-field
      glow curves were obtained by superposition of the experimentally obtained single
      field exposures. Feature vectors were composed of two kinds of features: those
      from deconvolution and those taken in the neighbourhood of several glow curve
      peaks. The inner product of the feature vectors was used to discriminate among
      the pure photon, pure proton and simulated mixed-field irradiations. In the pure
      cases, identification of radiation types is both straightforward and effective.
      Mixed-field discrimination did not succeed using deconvolution features, but the
      peak-neighbourhood features proved to discriminate reliably.

PMID- 16614092
TI  - A method for distinguishing between static and dynamic X-ray exposure of a
      personal TL-badge using the CCD camera TL reader.
AB  - This paper reports initial attempts to apply a thermoluminescent (TL) reader with
      CCD camera to identify cases of static and dynamic exposure of personal
      dosemeters to doses relevant for radiation protection. Standard MTS-N (LiF:Mg,Ti)
      and MCP-N (LiF:Mg,Cu,P) TL pellets with diameter of 4.5 mm and thickness of 0.9
      mm were used in a standard DOSACUS/RADOS personal dosimetry badge (holder). Pb,
      Cu and Al filters were installed instead of the standard Al 264 mg cm(-2) filters
      used in the RADOS badge. The badges were exposed statically and dynamically to X
      rays ranging from 28 keV (molybdenum anode) to 125 keV (tungsten anode) and to
      137Cs (662 keV) gamma rays. The absorbed doses (in tissue) ranged from 20 to 100
      mSv. Detectors were readout in the CCD reader and 2-D images were collected. The
      results obtained indicated that it was possible to identify the static, front
      exposure of the personal dosemeters equipped with Cu filter for doses >20 mGy for
      X rays up to 125 keV.

PMID- 16614093
TI  - Energy response of a two-dimensional sheet-type LiF:Mg,Cu,P TL dosemeter to
      photons.
AB  - A 2-D tissue-equivalent sheet-type dosemeter (NTL sheet) was developed using
      thermoluminescent material of LiF:Mg,Cu,P (NTL-250). The energy responses of the
      NTL sheet and NTL-250 powder were measured with 10-150 keV monoenergetic photons
      from synchrotron radiation at SPring-8. The sample was irradiated by a rotational
      method for the uniform irradiation with the narrow beam. Linearity of the NTL-250
      was confirmed up to 2 Gy. Energy responses of the NTL sheet and NTL-250 powder
      were close to that of soft tissue. On the other hand, the BaSO(4) sheet, which
      has been used practically, showed the response that the sensitivity approximately
      60 keV was 100 times higher than that for (60)Co gamma rays. Therefore the NTL
      sheet can be said to have excellent properties for dose measurements.

PMID- 16614094
TI  - The correlation between expression and localization of a foreign gene product in
      rice endosperm.
AB  - Glucagon-like peptide 1 (GLP-1) is a 30 amino acid peptide hormone involved in
      insulin stimulation that is dependent upon blood glucose levels. We have
      previously reported that when this short peptide gene was directly expressed
      under the control of a glutelin promoter and its signal peptide, it was not
      accumulated in transgenic rice seed due to gene silencing. However, when the
      modified GLP-1 (mGLP-1) gene was enlarged to 5xmGLP-1 (mGLPx5) by tandem repeat,
      no silencing was observed. The mGLPx5 peptide could be accumulated in rice seed
      and its localization was mainly limited to the endoplasmic reticulum (ER). We
      also investigated alternative cellular localization sites that would increase
      accumulation. The relationship between the expression level and localization was
      examined by attaching the chitinase signal peptide to mGLPx5 to direct it into
      the intercellular space (apoplast), or by expression as a fusion protein with
      glutelin by insertion into a variable region of the acidic subunit, thus
      directing the peptide to protein body II (PB II). Attachment of the KDEL ER
      retention signal to the 6xmGLP-1 (mGLPx6) or its fusion to the C-terminus of the
      13 kDa prolamin directed the peptide to the ER or PB I, respectively.
      Unexpectedly, these results indicated that mGLPx5 without any signal except for
      the glutelin signal peptide was accumulated to the greatest extent in rice
      endosperm. It can thus be concluded that the ER is a suitable intracellular
      organelle for accumulation of mGLPx5 peptide.

PMID- 16614095
TI  - The maize root plasma membrane H(+)-ATPase is regulated by a sugar-induced
      transduction pathway.
AB  - H(+)-ATPase, the key enzyme for the energization of ion and nutrient transport
      across the plasma membrane, is activated by phosphorylation-dependent 14-3-3
      binding. Since the involvement of 14-3-3 proteins in sugar sensing-regulated
      processes has recently emerged, here we address the question as to whether sugar
      sensing plays a role in the regulation of H(+)-ATPase. The data reported here
      show that sugar depletion inhibits the association of 14-3-3 proteins with H(+)
      ATPase by hampering phosphorylation of the 14-3-3 binding site of the enzyme. By
      using non-metabolizable disaccharides, we show that H(+)-ATPase regulation by 14
      3-3 proteins can involve a specific sugar perception and transduction mechanism.

PMID- 16614096
TI  - Are we ready for genome-wide association studies?

PMID- 16614097
TI  - Biorepositories: let's not lose what we have so carefully gathered!

PMID- 16614098
TI  - Is the association between cigarette smoking and breast cancer modified by
      genotype? A review of epidemiologic studies and meta-analysis.
AB  - Epidemiologic studies have examined the association between cigarette smoking and
      breast cancer risk according to genotype with increasing frequency, commensurate
      with the growing awareness of the roles genes play in detoxifying or activating
      chemicals found in cigarette smoke and in preventing or repairing the damage
      caused by those compounds. To date, approximately 50 epidemiologic studies have
      examined the association between smoking and breast cancer risk according to
      variation in genes related to carcinogen metabolism, modulation of oxidative
      damage, and DNA repair. Some of the findings presented here suggest possible
      effect modification by genotype. In particular, 14 epidemiologic studies have
      tended to show positive associations with long-term smoking among NAT2 slow
      acetylators, especially among postmenopausal women. Summary analyses produced
      overall meta-relative risk (RR) estimates for smoking of 1.2 [95% confidence
      interval (95% CI), 1.0-1.5] for rapid acetylators and 1.5 (95% CI, 1.2-1.8) for
      slow acetylators. After stratification by menopausal status, the meta-RR for
      postmenopausal slow acetylators was 2.4 (95% CI, 1.7-3.3), whereas similar
      analyses for the other categories showed no association. In addition, summary
      analyses produced meta-RRs for smoking of 1.1 (95% CI, 0.8-1.4) when GSTM1 was
      present and 1.5 (95% CI, 1.1-2.1) when the gene was deleted. Overall, however,
      interpretation of the available literature is complicated by methodologic
      limitations, including small sample sizes, varying definitions of smoking, and
      difficulties involving single nucleotide polymorphism selection, which likely
      have contributed to the inconsistent findings. These methodologic issues should
      be addressed in future studies to help clarify the association between smoking
      and breast cancer.

PMID- 16614099
TI  - The heritability of mammographically dense and nondense breast tissue.
AB  - BACKGROUND: Percent mammographic density (PMD) is a risk factor for breast
      cancer. Our previous twin study showed that the heritability of PMD was 63%. This
      study determined the heritabilities of the components of PMD, the areas of dense
      and nondense tissue in the mammogram. METHODS: We combined two twin studies
      comprising 571 monozygous and 380 dizygous twin pairs recruited from Australia
      and North America. Dense and nondense areas were measured using a computer
      assisted method, and information about potential determinants was obtained by
      questionnaire. Under the assumptions of the classic twin model, we estimated the
      heritability of the log dense area and log nondense area and the genetic and
      environmental contributions to the covariance between the two traits, using
      maximum likelihood theory and the statistical package FISHER. RESULTS: After
      adjusting for measured determinants, for each of the log dense area and the log
      nondense area, the monozygous correlations were greater than the dizygous
      correlations. Heritability was estimated to be 65% (95% confidence interval, 60
      70%) for dense area and 66% (95% confidence interval, 61-71%) for nondense area.
      The correlations (SE) between the two adjusted traits were -0.35 (0.023) in the
      same individual, -0.26 (0.026) across monozygous pairs, and -0.14 (0.034) across
      dizygous pairs. CONCLUSION: Genetic factors may play a large role in explaining
      variation in the mammographic areas of both dense and nondense tissue. About two
      thirds of the negative correlation between dense and nondense area is explained
      by the same genetic factors influencing both traits, but in opposite directions.

PMID- 16614100
TI  - The impact of acculturation on awareness of genetic testing for increased cancer
      risk among Hispanics in the year 2000 National Health Interview Survey.
AB  - Previous studies suggest disparities in use of preventive cancer services among
      U.S. Hispanics are partly explained by knowledge and access factors. One area of
      emerging interest is uptake of genetic counseling and testing services by
      underserved populations. This study aims to estimate the percentage of Hispanics
      in five ethnic subgroups who are aware of genetic testing for inherited cancer
      risk, and to assess the influence of acculturation factors primarily related to
      language on test awareness. Weighted data from 4,313 Hispanic respondents (age
      >25 years) in the year 2000 National Health Interview Survey were analyzed.
      Overall, 20.6% of Hispanics had heard of genetic testing for cancer risk, with
      percentages highest among Puerto Ricans (27.3%) and lowest among Mexicans
      (14.3%). Completing the interview in Spanish and English [odds ratio (OR), 0.52;
      95% confidence interval (95% CI), 0.35-0.78], or only Spanish (OR, 0.60; 95% CI,
      0.42-0.86), was inversely associated with test awareness (reference group, only
      English). Having an intermediate (OR, 0.66; 95% CI, 0.48-0.90) or low (OR, 0.63;
      95% CI, 0.39-1.01) level of English language preference was also inversely
      associated (reference, high level) whereas being born outside the United States
      was weakly associated (OR, 0.80; 95% CI, 0.57-1.11). Estimates were adjusted for
      age, education, ethnicity, parents' cancer history, health care access, and
      selected health behaviors and beliefs. Results of this national survey indicate
      that acculturation factors related to language may affect cancer genetic test
      awareness in Hispanics. These factors must be taken into account when informing
      individuals about the role of genetics in cancer risk and providing cancer
      genetic health services.

PMID- 16614101
TI  - Interindividual variations in DNA adduct levels assessed by analysis of multiple
      genetic polymorphisms in smokers.
AB  - Genetic polymorphisms in genes involved in processes that affect DNA damage may
      explain part of the large interindividual variation in DNA adduct levels in
      smokers. We investigated the effect of 19 polymorphisms in 12 genes involved in
      carcinogen metabolism, DNA repair, and oxidant metabolism on DNA adduct levels
      (determined by (32)P post-labeling) in lymphocytes of 63 healthy Caucasian
      smokers. The total number of alleles that were categorized as putatively high
      risk alleles seemed associated with bulky DNA adduct levels (P = 0.001).
      Subsequently, to investigate which polymorphisms may have the highest
      contribution to DNA adduct levels in these smokers, discriminant analysis was
      done. In the investigated set of polymorphisms, GSTM1*0 (P < 0.001), mEH*2 (P =
      0.001), and GPX1*1 (P < 0.001) in combination with the level of exposure (P <
      0.001) were found to be key effectors. DNA adduct levels in subjects with a
      relatively high number of risk alleles of these three genes were >2-fold higher
      than in individuals not having these risk alleles. Noteworthy, all three genes
      are involved in deactivation of reactive carcinogenic metabolites. This study
      shows that analysis of multiple genetic polymorphisms may predict the
      interindividual variation in DNA adduct levels upon exposure to cigarette smoke.
      It is concluded that discriminant analysis presents an important statistical tool
      for analyzing the effect of multiple genotypes on molecular biomarkers.

PMID- 16614102
TI  - Changes in cancer registry coding for lymphoma subtypes: reliability over time
      and relevance for surveillance and study.
AB  - Because lymphoma comprises numerous histologic subtypes, understanding the
      reasons for ongoing increases in its incidence requires surveillance and
      etiologic study of these subtypes. However, this research has been hindered by
      many coexisting classification schemes. The Revised European American
      classification of Lymphoid Neoplasms (REAL)/WHO system developed in 1994 and now
      used in clinical settings was not incorporated into the International
      Classification of Diseases-Oncology (ICD-O), used by cancer registries, until the
      release of the third edition (ICD-O-3) in 2001. Studies including patients
      diagnosed before 2001 may have codes from earlier ICD-O versions that must be
      converted to ICD-O-3 and have higher proportions of unclassified (e.g., lymphoma
      and not otherwise specified) cases. To better understand (a) the agreement of
      computer-converted ICD-O-3 codes to ICD-O-3 codes generated directly from
      diagnostic pathology reports and (b) the reproducibility of unclassified status,
      we reviewed a population-based series of diagnostic pathology reports for
      lymphoma patients diagnosed before (1988-1994; n = 1,493) and after (1998-2000; n
      = 1,527) the REAL/WHO scheme was introduced. Overall, computer- and coder
      assigned ICD-O-3 codes agreed for 77% of patients in both groups and improved
      slightly (82%) when codes were grouped. The most common lymphoma subtypes,
      diffuse large B cell and follicular, had relatively good reliability (84-89%)
      throughout the study period. T-cell and natural killer cell lymphomas had worse
      agreement than B-cell lymphomas, even when grouped. Many (42-43%) lymphomas
      reported as unclassifiable could be assigned a subtype upon pathology report
      review. These findings suggest that the study of lymphoma subtypes could be
      improved by (a) use of more standardized terminology in pathology reports, (b)
      grouping individual ICD-O-3 codes to reduce misclassification bias, and (c)
      routine secondary editing of unclassified lymphomas by central cancer registries.

PMID- 16614103
TI  - Relationship between urinary 15-F2t-isoprostane and 8-oxodeoxyguanosine levels
      and breast cancer risk.
AB  - To evaluate the role of oxidative stress in breast cancer, we measured urinary
      levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) and 8-oxodeoxyguanosine (8-oxodG)
      in 400 cases and 401 controls, participants of the Long Island Breast Cancer
      Study Project. We also analyzed the effect of different factors that are
      associated with oxidative stress and might influence 15-F(2t)-IsoP and 8-oxodG
      levels. We observed a statistically significant trend in breast cancer risk with
      increasing quartiles of 15-F(2t)-IsoP levels [odds ratio (OR), 1.25; 95%
      confidence interval (95% CI), 0.81-1.94; OR, 1.53; 95% CI, 0.99-2.35; OR, 1.88;
      95% CI, 1.23-2.88, for the 2nd, 3rd, and 4th quartile relative to the lowest
      quartile, respectively; P(trend) = 0.002]. Although it is possible that increased
      levels may reflect the stress associated with recent treatment, the positive
      association was also observed when the analyses were restricted to case women for
      whom chemotherapy and radiation therapy had not yet been initiated at the time of
      the urine collection. The association with the highest quartile compared with
      lowest quartile of 15-F(2t)-IsoP was similar across strata of age, physical
      activity, fruit and vegetable intake, alcohol intake, cigarette smoking, body
      mass index, and menopausal status. We did not observe any association of breast
      cancer risk with 8-oxodG levels, but when cases with radiation treatment were
      removed from the analysis, a significant inverse trend (P = 0.04) was observed.
      Among controls, levels of 15-F(2t)-IsoP were higher among current cigarette
      smokers but did not differ by the amount of physical activity, fruit and
      vegetable intake, alcohol intake, body mass index, and menopausal status. Among
      controls, levels of 8-oxodG were higher among postmenopausal women and current
      and former cigarette smokers but did not differ by the other factors. In summary,
      our results suggest that urinary markers of lipid peroxidation and oxidative DNA
      damage may be associated with breast cancer risk.

PMID- 16614104
TI  - Assessment of DNA damage in WBCs of workers occupationally exposed to fumes and
      aerosols of bitumen.
AB  - We conducted a cross-shift study with 66 bitumen-exposed mastic asphalt workers
      and 49 construction workers without exposure to bitumen. Exposure was assessed
      using personal monitoring of airborne bitumen exposure, urinary 1-hydroxypyrene
      (1-OHP), and the sum of 1-, 2 + 9-,3-,4-hydroxyphenanthrene (OHPH). Genotoxic
      effects in WBC were determined with nonspecific DNA adduct levels of 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxodGuo) and the formation of DNA strand breaks and
      alkali-labile sites. Concentration of fumes and aerosols of bitumen correlated
      significantly with the concentrations of 1-OHP and OHPH after shift (r(s) = 0.27;
      P = 0.03 and r(s) = 0.55; P < 0.0001, respectively). Bitumen-exposed workers had
      more DNA strand breaks than the reference group (P < 0.0001) at both time points
      and a significant correlation with 1-OHP and OHPH in the postshift urines (r(s) =
      0.32; P = 0.001 and r(s) = 0.27; P = 0.004, respectively). Paradoxically, we
      measured higher levels of DNA strand breaks, although not significant, in both
      study groups before shift. 8-OxodGuo adduct levels did not correlate with DNA
      strand breaks. Further, 8-oxodGuo levels were associated neither with personal
      exposure to bitumen nor with urinary metabolite concentrations. Significantly
      more DNA adducts were observed after shift not only in bitumen-exposed workers
      but also in the reference group. Only low-exposed workers had significantly
      elevated 8-oxodGuo adduct levels before as well as after shift (P = 0.0002 and P
      = 0.02, respectively). Our results show that exposure to fumes and aerosols of
      bitumen may contribute to an increased DNA damage assessed with strand breaks.

PMID- 16614105
TI  - Do testicular seminoma and nonseminoma share the same etiology? Evidence from an
      age-period-cohort analysis of incidence trends in eight European countries.
AB  - The incidence of the two main clinical subentities of testicular germ cell cancer
      (seminoma and nonseminoma) is increasing throughout Europe. Most studies have
      revealed little variation in risk factors between the two subtypes. This study
      compared generation-specific trends in eight European countries, hypothesizing
      that similar temporal pattern by birth cohort implied that seminoma and
      nonseminoma had a largely comparable etiology. The results are presented using
      the age-period-cohort model and the nonidentifiability problem highlighted by
      partitioning the age, period, and cohort effects in terms of their linear and
      curvature component parts, assuming a priori that cohort effects predominated.
      Despite uniform overall increases by calendar period, declining rates of
      nonseminoma but not pure seminoma were observed in the majority of countries
      during the 1990s. The subtype trends were, however, largely analogous on a birth
      cohort scale. Notable observations were a decline in rates of both subtypes among
      recent birth cohorts in Switzerland and a short-term wartime effect in several
      countries, involving an attenuation of increasing risk of both subtypes in men
      born in 1940 to 1945. Departures from the steady increases in testicular cancer
      over time were likely to occur for nonseminomas some years ahead of seminoma on a
      period scale. The importance of birth cohort coincided with the view that given a
      short time interval of susceptibility to exposures earlier in life and a
      biologically constant time to diagnosis, all temporal changes in rate-limiting
      exposures should appear as generational effects. Trends in seminoma and
      nonseminoma conform to largely the same temporal patterns on this scale, implying
      that they share important etiologic factors.

PMID- 16614106
TI  - GSTP1 genetic polymorphism is associated with a higher risk of DNA damage in
      pesticide-exposed fruit growers.
AB  - Pesticide exposure is associated with various neoplastic diseases and congenital
      malformations. Animal studies also indicated that pesticides may be metabolized
      by cytochrome P450 3A5 (CYP3A5) enzymes, paraoxonases (PON1 and PON2), or
      glutathione S-transferases (GSTM1, GSTT1, and GSTP1). However, little is known
      about the genotoxicity of pesticides in people with various genetic polymorphisms
      of human CYP3A5, PON1, PON2, GSTM1, GSTT1, and GSTP1. Thus, this study was
      designed to investigate whether various metabolic genotypes are more susceptible
      to DNA damage in pesticide-exposed fruit growers. Using the Comet assay, the
      extent of DNA damage was evaluated in the peripheral blood of 91 fruit growers
      who experienced pesticide exposure and 106 unexposed controls. Questionnaires
      were administered to obtain demographic data, cigarette smoking habits, medical,
      and occupational histories. The genotypes for CYP3A5, PON1, PON2, GSTM1, GSTT1,
      and GSTP1 genes were identified by PCR. The results showed that subjects
      experiencing high or low pesticide exposure had a significantly greater DNA tail
      moment (DAN damage) than did controls. The multiple regression model also
      revealed that age (P < 0.01), high pesticide exposure (P < 0.01), low pesticide
      exposure (P < 0.01), and CYP3A5 (P = 0.04) and GSTP1 (P = 0.02) genotypes were
      significantly associated with an increased DNA tail moment. Further analysis of
      environmental and genetic interactions revealed a significant interaction for
      GSTP1 genotypes to influence DNA tail moment for the high pesticide exposure
      group. These results suggest that individuals with susceptible metabolic GSTP1
      genotypes may experience an increased risk of DNA damage elicited by pesticide
      exposure.

PMID- 16614107
TI  - GSTM1 and CYP1A1 polymorphisms, tobacco, air pollution, and lung cancer: a study
      in rural Thailand.
AB  - OBJECTIVES: The Lampang Province is situated in the northern region of Thailand.
      Incidence rates of lung cancer are high for Asian standards, particularly in
      women. This study was conducted to quantify the risk of lung cancer associated
      with exposures prevalent in the area and to investigate possible interactions
      with genetic susceptibility. The presence of several large open-cast coal mines
      from 1955 close to electricity-generating plants was a particular focus of
      concern. METHODS: Two-hundred and eleven cases of primary lung cancers diagnosed
      in 1993 to 1995 and residents in the province were recruited at the Lampang
      Provincial Hospital (main referral center for treatment of the disease). Two sets
      of controls, frequency-matched to the cases by sex and age, were recruited (a)
      from the resident population (202 interviewed) and (b) from patients admitted to
      the hospital for diseases predominantly unrelated to tobacco smoking (211
      interviewed). Sociodemographic information, complete residential history, and
      characteristics of the household (place of cooking, cooking fuel, and heating
      fuels), occupational history, and history of tobacco smoking were obtained by
      interview. Cases and controls ( approximately 50% of the population-based series)
      provided a blood sample. A point source air pollution exposure index was
      calculated for each village/township reported in residential histories based on
      the linear distance from the Mae Moh Center (the area of the electricity
      generating plants), the year-specific gaseous (SO(2) and NO(2)) or total
      suspended particulate emissions from the Mae Moh Power Plant, and the percentage
      of wind from the center. Odds ratios (OR) for the disease associated with
      categorical variables were estimated within unconditional logistic regression.
      Extraction of genomic DNA and genotyping of variants in CYP1A1 and GSTM1 were
      conducted to assess the extent of modification of risk by these genes that are
      involved in the metabolism of polycyclic aromatic hydrocarbons, a common
      component of the exposures. RESULTS: Overall, there was no evidence of relevant
      differences in the socioeconomic level of the three groups. The two control sets
      were similar with respect to lifelong tobacco habit and were subsequently pooled
      in analyses. Never-smokers were 7% of men and 33% of women. Smoking of local
      traditional products unfiltered and high in tar content is a common habit in the
      rural female population. ORs associated with smoking increased with duration of
      the habit and average daily amount, being 4.9 [95% confidence interval (95% CI),
      2.5-9.7] for smokers of > or =7 cigarettes/d and 3.3 (95% CI, 1.7-6.2) for
      duration of 41 years or longer compared with nonsmokers. Smoking of local
      products was associated with an independent OR of 3.1 (95% CI, 1.7-5.6) adjusted
      for lifelong cumulative amount of tobacco smoked. Although most smokers had the
      habit for at least 16 years, the daily consumption was low compared with Western
      standards. Other potential sources of exposure to lung carcinogens (emission from
      the power-generating plants and domestic burning of coal and wood for cooking and
      heating) were not associated with increased risk of lung cancer. None of the
      three polymorphisms examined increased the risk of lung cancer or modified the
      risk associated with tobacco smoking. CONCLUSION: In this rural population, 96%
      of male and 64% of female lung cancer incidence were explained by tobacco
      smoking. None of the potential sources of air pollution deriving from the
      combustion of coal and wood, or polymorphisms in the CYP1A1 gene or deletion of
      the GSTM1 had an effect on the risk of lung cancer, either together or
      separately.

PMID- 16614108
TI  - Association of the progesterone receptor gene with breast cancer risk: a single
      nucleotide polymorphism tagging approach.
AB  - Association studies on susceptibility to breast cancer using single nucleotide
      polymorphisms (SNP) in the progesterone receptor (PGR) gene have been previously
      published, but the results have been inconclusive. We used a comprehensive SNP
      tagging approach to search for low-penetrance susceptibility alleles in a study
      of up to 4,647 cases and 4,564 controls, in a two-stage study design. We
      identified seven tagging SNPs using genotype data from the National Institute of
      Environmental Health Sciences (NIEHS) Environmental Genome Project and typed
      these, and an additional three SNPs, in 2,345 breast cancer cases and 2,284
      controls (set 1). Three SNPs showed no evidence for association and were not
      studied further, whereas seven SNPs (rs11571171, rs7116336, rs660149, rs10895068,
      rs500760, rs566351, and rs1042838) exhibited significant associations at P < 0.1
      using either a heterogeneity or trend test and progressed to be genotyped in set
      2. After both stages, only one SNP was significantly associated with an increased
      risk of breast cancer - the PGR-12 (rs1042638) V660L valine to leucine
      polymorphism [VL heterozygotes (odds ratio, 1.13; 95% confidence interval, 1.03
      1.24) and the LL homozygotes (odds ratio, 1.30; 95% confidence interval, 0.98
      1.73), P(het) = 0.008, P(trend) = 0.002]. Similar estimates were obtained in a
      combined analysis of our data with those from three other published studies. We
      conclude that the 660L allele may be associated with a moderately increased risk
      of breast cancer, but that other common SNPs in the PGR gene are unlikely to be
      associated with a substantial risk of breast cancer.

PMID- 16614109
TI  - Hepatitis viruses, alcohol, and tobacco in the etiology of hepatocellular
      carcinoma in Italy.
AB  - Mortality rates of hepatocellular carcinoma (HCC) are high in Italy compared with
      other Western countries. To elucidate further the role of hepatitis B virus
      (HBV), hepatitis C virus (HCV), alcohol drinking, and tobacco smoking in the
      etiology of HCC, we carried out a hospital-based case-control study in two areas
      of Italy: the province of Pordenone in the Northeast and the town of Naples in
      the South. A total of 229 HCC cases (median age, 66 years) and 431 controls
      (median age, 65 years) answered a questionnaire and provided blood samples
      between 1999 and 2002. Odds ratios (OR), percent attributable risks, and
      corresponding 95% confidence intervals were computed using unconditional multiple
      logistic regression. ORs for hepatitis B surface antigen (HBsAg) positive versus
      HBsAg negative and for anti-HCV antibody positive versus anti-HCV antibody
      negative were 20.2 and 15.6, respectively. Positivity for both markers was
      associated with an OR of 51.6. Sensitive molecular techniques applied to sera in
      a subset of HCC cases disclosed a very small number of occult hepatites. Maximal
      lifetime alcohol intake of > or =35 versus <7 drinks/wk was associated with an
      HBV/HCV adjusted OR of 5.9. Tobacco smoking was unrelated to HCC risk overall but
      seemed to enhance HCC risk among virus carriers. Overall, 61% of HCC were
      attributable to HCV, 13% to HBV, and 18% to heavy alcohol drinking. In
      conclusion, our study confirms the importance of HCV in HCC etiology in Italy
      where the widespread dissemination of the virus dates back four or five decades.

PMID- 16614110
TI  - Plasma C-reactive protein and risk of colorectal cancer in a nested case-control
      study: Japan Public Health Center-based prospective study.
AB  - C-reactive protein is a biomarker indicating inflammation in the body. We
      measured plasma C-reactive protein to assess whether this biomarker could predict
      subsequent colorectal cancer incidence. A nested case-control study was conducted
      within a Japan Public Health Center-based prospective study. During a 11.5-year
      follow-up, 375 newly diagnosed colorectal cancers were identified in a cohort of
      38,373 adults who had returned the baseline questionnaire and provided blood
      samples. Two controls were selected from the cohort for each case matched by age,
      sex, study area, date of blood drawn, and fasting time at blood donation. The
      odds ratio of colorectal cancer for plasma C-reactive protein was estimated using
      a conditional logistic regression model adjusted for pack-years of smoking, body
      mass index, alcohol consumption, physical exercise, and family history of
      colorectal cancer. The highest quartile group of plasma C-reactive protein was
      significantly associated with colorectal cancer compared with the lowest group
      (odds ratio, 1.6; 95% confidence interval, 1.1-2.5; P(trend) = 0.053). The
      association became clearer after excluding cases of rectal cancer (P(trend) =
      0.041) and limiting colorectal cancer to the intramucosal type (P(trend) =
      0.017). This association was unchanged after deletion of the first 2-year cases.
      In conclusion, plasma levels of C-reactive protein were associated with a
      subsequent risk of colon cancer. Inflammation may be involved at the early stage
      of colon tumor growth.

PMID- 16614111
TI  - Evidence for an important role of alcohol- and aldehyde-metabolizing genes in
      cancers of the upper aerodigestive tract.
AB  - BACKGROUND: Incidence and mortality rates of upper aerodigestive tract cancers in
      Central Europe are among the highest in the world and have increased
      substantially in recent years. This increase is likely to be due to patterns of
      alcohol and tobacco consumption. Genetic susceptibility to upper aerodigestive
      tract cancer in relation to such exposures is an important aspect that should be
      investigated among populations in this region. METHODS: A multicenter case
      control study comprising 811 upper aerodigestive tract cancer cases and 1,083
      controls was conducted in: Bucharest (Romania), Lodz (Poland), Moscow (Russia),
      Banska Bystrika (Slovakia), and Olomouc and Prague (Czech Republic). We analyzed
      six SNPs in three genes related to ethanol metabolism: alcohol dehydrogenase 1B
      and 1C (ADH1B, ADH1C) and aldehyde dehydrogenase 2 (ALDH2). RESULTS: The ADH1B
      histidine allele at codon 48 was associated with a decreased risk of upper
      aerodigestive tract cancer; odds ratios (OR) were 0.36 [95% confidence interval
      (95% CI), 0.17-0.77] for medium/heavy drinkers and 0.57 (95% CI, 0.36-0.91) for
      never/light drinkers. Moderately increased risks were observed for the ADH1C
      (350)Val allele (OR, 1.19; 95% CI, 0.98-1.55) and ADH1C (272)Gln allele (OR,
      1.24; 95% CI, 0.98-1.55). Medium/heavy drinkers who were heterozygous or
      homozygous at ALDH2 nucleotide position 248 were at a significantly increased
      risk of upper aerodigestive tract cancer (OR, 1.76; 95% CI, 1.13-2.75; OR, 5.79;
      95% CI, 1.49-22.5, respectively), with a significant dose response for carrying
      variant alleles (P = 0.0007). Similar results were observed for the ALDH2 +82A>G
      and ALDH2 -261C>T polymorphisms. When results were analyzed by subsite, strong
      main effects were observed for squamous cell carcinoma of the esophagus for all
      six variants. Among the 30% of the population who were carriers of at least one
      ALDH2 variant, the attributable fraction among carriers (AF(c)) was 24.2% (5.7
      38.3%) for all upper aerodigestive tract cancers, increasing to 58.7% (41.2
      71.0%) for esophageal cancer. Among carriers who drank alcohol at least thrice to
      four times a week, the AF(c) for having at least one ALDH2 variant was 49% (21.3
      66.8%) for all upper aerodigestive tract cancers, increasing to 68.9% (42.9
      83.1%) for esophageal cancer. CONCLUSIONS: Polymorphisms in the ADH1B and ALDH2
      genes are associated with upper aerodigestive tract cancer in Central European
      populations and interact substantially with alcohol consumption.

PMID- 16614112
TI  - Pancreatic cancer genetic epidemiology consortium.
AB  - We have organized the Pancreatic Cancer Genetic Epidemiology (PACGENE) Consortium
      to identify susceptibility genes in familial pancreatic cancer (FPC). The
      Consortium comprises seven data collection centers, a statistical genetics core,
      and a pathology/archival genotyping core. We recruit kindreds containing two or
      more affected blood relatives ascertained through incident pancreatic
      adenocarcinoma cases, physician referrals, and/or through Internet recruitment.
      Accrual to a database containing core clinical, demographic, lifestyle, and
      family history information from questionnaires is ongoing, along with biospecimen
      collection. To date, 13,147 patients have been screened for family history, of
      whom 476 (50% male) probands and 1,912 of their adult (99% unaffected) relatives
      have been enrolled. Of these, 379 kindreds meet criteria for FPC, having at least
      two first-degree relatives with pancreatic cancer. Cumulative incidence curves
      using available age of diagnosis (onset) among and affected relatives were
      compared with those for incident pancreatic cancer cases reported to 13 U.S.
      Surveillance Epidemiology and End Results (SEER) sites from 1973 to 2000 (N =
      72,700). The mean age +/- SD at diagnosis among 466 PACGENE probands and 670
      affected relatives was 64.1 +/- 11.8 and was 65.4 +/- 11.6 for the subset of 369
      FPC probands and 429 relatives. Both samples were significantly younger than the
      mean age at diagnosis in the SEER population (70.0 +/- 12.1 years; differences in
      curves versus SEER, P < 0.001). Age at diagnosis (excluding probands) in FPC
      kindreds does not decrease with increasing number of affected individuals. In our
      sample, younger age at diagnosis was observed whether we grouped probands by
      recruitment sites that predominantly recruited through high-risk referrals, or
      through screening all pancreatic cancer patients for family history. Linkage
      studies are ongoing. The PACGENE Consortium will be a valuable family-based
      resource that will greatly enhance genetic epidemiology research in pancreatic
      cancer.

PMID- 16614113
TI  - Aberrant neuropeptide Y and macrophage inhibitory cytokine-1 expression are early
      events in prostate cancer development and are associated with poor prognosis.
AB  - Studies to elucidate dysregulated gene expression patterns in premalignant
      prostate lesions have identified several candidate genes with the potential to be
      targeted to prevent the development and progression of prostate cancer and act as
      biomarkers of early disease. Herein, we explored the importance of two proteins,
      neuropeptide Y (NPY) and macrophage inhibitory cytokine-1 (MIC-1), as biomarkers
      of preinvasive prostate disease and investigated the relationship of expression
      to biochemical recurrence following treatment for localized prostate cancer. NPY
      and MIC-1 protein expression was determined by immunohistochemistry on tissue
      microarrays containing 1,626 cores of benign, low-grade prostatic intraepithelial
      neoplasia (PIN), high-grade PIN (HGPIN), and prostate cancer tissue from 243
      radical prostatectomy patients. Both NPY and MIC-1 showed higher proportional
      immunostaining in HGPIN and prostate cancer compared with benign epithelium (P <
      0.0001). NPY and MIC-1 immunostaining was higher in low-grade PIN compared with
      other benign tissues (both P < 0.0001) and was equivalent to immunostaining in
      HGPIN. NPY immunostaining of prostate cancer was independently associated with
      relapse, after adjusting for traditional prognostic factors, as a categorical
      variable in 20% intervals (P = 0.0449-0.0103) and as a continuous variable (P =
      0.0017). Low MIC-1 immunostaining (20% categories) was associated with pathologic
      stage >2C after adjusting for predictors of pathologic stage (P = 0.3894-0.0176).
      This is the first study to show that altered NPY and MIC-1 expression are
      significantly associated with prostate cancer progression and suggests that these
      molecules be developed further as biomarkers in the management of prostate
      disease.

PMID- 16614114
TI  - Heme and chlorophyll intake and risk of colorectal cancer in the Netherlands
      cohort study.
AB  - BACKGROUND: The evidence for red meat as a determinant of colorectal cancer
      remains equivocal, which might be explained by differences in heme content. Heme
      is the pro-oxidant, iron-containing porphyrin pigment of meat and its content
      depends on the type of meat. Chlorophyll from green vegetables might modify this
      association. METHODS: The Netherlands Cohort Study was initiated in 1986 when a
      self-administered questionnaire on risk factors for cancer was completed by
      120,852 subjects ages 55 to 69 years. After 9.3 years of follow-up through the
      Cancer Registry, 1,535 incident colorectal cancer cases (869 men and 666 women)
      were available. Nineteen of the 150 items in the validated dietary questionnaire
      related to consumption of specific types of fresh and processed meat. Heme iron
      content was calculated as a type-specific percentage of the total iron content
      and chlorophyll content of vegetables was derived from the literature. RESULTS:
      Multivariate rate ratios for quintiles of heme iron intake and colon cancer were
      1.00, 0.98, 1.04, 1.13, and 1.29 (P(trend) = 0.10) among men and 1.00, 1.31,
      1.44, 1.18, and 1.20 (P(trend) = 0.56) among women, respectively. No consistent
      associations were observed for rectal cancer. Rate ratios for colon cancer
      increased across successive quintiles of the ratio of heme/chlorophyll among men
      only (1.00, 1.08, 1.01, 1.32, and 1.43; P(trend) = 0.01). No associations were
      observed between fresh meat and colorectal cancer. CONCLUSION: Our data suggest
      an elevated risk of colon cancer in men with increasing intake of heme iron and
      decreasing intake of chlorophyll. Further research is needed to confirm these
      results.

PMID- 16614115
TI  - Inflammation, genetic polymorphisms in proinflammatory genes TNF-A, RANTES, and
      CCR5, and risk of pancreatic adenocarcinoma.
AB  - Adenocarcinoma of the exocrine pancreas is the fourth leading cause of cancer
      related death in men and women in the U.S. Cytokines and other proinflammatory
      mediators have been implicated in inflammatory pancreatic diseases including
      pancreatitis and cancer. We analyzed cytokine gene polymorphisms as risk factors
      for pancreatic cancer using questionnaire data obtained by in-person interviews
      and germ line DNA collected in a population-based case-control study of
      pancreatic cancer (532 cases and 1,701 controls) conducted in the San Francisco
      Bay Area. We used mass spectrometry and gel-based methods to genotype 308 cases
      and 964 population-based controls. Odds ratios (OR) and 95% confidence intervals
      (CI) were estimated using logistic regression analysis and included adjustment
      for age, sex, and smoking. We assessed potential interactions between these
      polymorphisms, proinflammatory conditions (e.g., pancreatitis, ulcer, and
      obesity), and smoking as risk factors for pancreatic cancer. There was no overall
      association between pancreatic cancer risk and tumor necrosis factor-alpha (TNF-A
      -308G/A), regulated upon activation, normally T cell-expressed, and presumably
      secreted (RANTES -403G/A), and CC chemokine receptor 5 (CCR5-Delta32)
      polymorphisms. There was a nearly 7-fold increased relative risk estimate for
      pancreatic cancer in individuals with a history of pancreatitis (adjusted OR,
      6.9; 95% CI, 3.4-14.1). Among patients with pancreatic cancer, pancreatitis was
      significantly associated with TNF-A -308 GA + AA (OR, 3.1; 95% CI, 1.3-7.4) and
      with RANTES -403 GA + AA (OR, 2.3; 95% CI, 1.0-5.4). There was evidence for a
      possible interaction between current active smoking and CCR5-32del. Our results
      lend support for the hypothesis that proinflammatory gene polymorphisms, in
      combination with proinflammatory conditions, may influence the development of
      pancreatic cancer.

PMID- 16614116
TI  - A longitudinal investigation of mammographic density: the multiethnic cohort.
AB  - Mammographic densities are hypothesized to reflect the cumulative exposure to
      risk factors that influence breast cancer incidence. This report analyzed percent
      densities over time and explored predictors of density change in relation to age.
      The study population consisted of 607 breast cancer cases and 667 frequency
      matched controls with 1,956 and 1,619 mammographic readings, respectively.
      Mammograms done over >20 years and before a diagnosis of breast cancer were
      assessed for densities using a computer-assisted method. Using multilevel
      modeling to allow for repeated measurements, we estimated the effect of
      ethnicity, case status, reproductive characteristics, hormonal therapy, body mass
      index, and soy intake on initial status and longitudinal change. After
      integrating the area under the percent density curve, cumulative percent density
      was compared with age-specific breast cancer rates in Hawaii. Percent densities
      decreased approximately 5.6% per 10 years but a nonlinear effect indicated a
      faster decline earlier in life. Cumulative percent densities and age-specific
      breast cancer rates increased at very similar rates; both standardized regression
      coefficients were >0.9. Japanese ancestry, overweight, estrogen/progestin
      treatment, and, to a lesser degree, estrogen-only therapy predicted a slower
      decline in densities with age. Case status and adult soy intake were related to
      higher densities whereas overweight and having any child were associated with
      lower densities at initial status. Risk factors that influence the decline in
      mammographic densities over time may be important for breast cancer prevention
      because cumulative percent densities may reflect the age-related increase in
      breast cancer risk.

PMID- 16614117
TI  - Bladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal
      bladder epithelium.
AB  - Schistosoma haematobium-infected patients are more likely to develop bladder
      cancer and be more exposed to carcinogenic N-nitroso compounds than uninfected
      patients. As N7-methylguanine is a marker of exposure to methylating agents of
      this type, we have measured N7-methyldeoxyguanosine 3'-monophosphate (N7-MedGp)
      by (32)P postlabeling. DNA was isolated from 42 paired normal and tumor tissue of
      Egyptians with bladder cancer. N7-MedGp was detected in DNA from 93% of the
      tumors and 74% of the normal bladder tissue samples. Adduct levels were highly
      variable and ranged from 0.04 to 6.4 and from 0.02 to 0.72 micromol/mol
      deoxyguanosine 3'-monophosphate (dGp) in tumor and normal DNA, respectively. N7
      MedGp levels in normal and tumor DNA were highly correlated with one another (P =
      0.007). The mean difference (95% confidence interval) in adduct levels between
      tumor and normal DNA was 0.21 (0.13-0.32) micromol/mol dGp and this was
      statistically significant (P < 0.001). The adduct ratio (tumor DNA/normal DNA)
      varied between 0.2 and 136 (median, 4.6). N7-MedGp levels were not associated
      with gender, age, or the presence of schistosomiasis. However, lower N7-MedGp
      levels were found in normal DNA from individuals lacking the GSTM1 gene (P =
      0.03) but not the GSTT1 gene or in subjects with the Ile105Val GSTP1
      polymorphism. These results show that exposure to methylating agents is
      widespread and suggest that such exposure may play a role both in tumor
      initiation and progression.

PMID- 16614118
TI  - Haplotype analysis of common vitamin D receptor variants and colon and rectal
      cancers.
AB  - Inherited variants of the vitamin D receptor (VDR) gene may influence cancer risk
      by altering the effect of vitamin D on cell growth and homeostasis. Studies have
      examined genotypes for common VDR polymorphisms, including a single nucleotide
      polymorphism (SNP) detected by Bsm1, a polyadenosine [poly(A)] repeat
      polymorphism, and a SNP detected by Fok1, as candidates for susceptibility to
      cancer, but most have not evaluated haplotypes for these markers. We investigated
      haplotypes for these polymorphisms in case-control studies of colon cancer (1,811
      cases and 1,451 controls) and rectal cancer (905 cases and 679 controls). We used
      the expectation-maximization algorithm to estimate haplotypes for White,
      Hispanic, African-American, and Asian subjects, tested for differences in VDR
      haplotype distribution, and calculated odds ratios (OR) for association between
      haplotype and cancer. The distribution of haplotypes differed by race or ethnic
      group, but four common haplotypes accounted for the majority of alleles in all
      groups. VDR haplotype distributions differed between colon cancer cases and
      controls (P = 0.0004). The common haplotype bLF, containing Bsm1 b (Bsm1
      restriction site present), poly(A) long (18-22 repeats), and Fok1 F (restriction
      site absent) was associated with increased risk of colon cancer, OR 1.15 (95%
      confidence interval, 1.03-1.28), as was the rare haplotype BLF, containing Bsm1 B
      (restriction site absent), poly(A) long, and Fok1 F (OR, 2.40; 95% confidence
      interval, 1.43-4.02). No case-control differences were detected for rectal
      cancer. In this analysis, haplotypes of the VDR influenced risk of colon cancer,
      but haplotype variables had only slightly better ability to explain case-control
      differences than genotype variables.

PMID- 16614119
TI  - C-peptide, insulin-like growth factor binding protein-1, glycosylated hemoglobin,
      and the risk of distal colorectal adenoma in women.
AB  - BACKGROUND: Determinants of insulin secretion and insulin-like growth factors
      (IGF) have been directly associated with risk for colorectal cancer. However, few
      studies have evaluated whether these factors are also associated with risk of
      colorectal adenoma, the main precursor lesion to colorectal cancer. METHODS: We
      identified 380 distal colorectal adenoma cases diagnosed between 1989 and 1998
      and 380 controls among nondiabetic women from the cohort of 32,826 women, nested
      in the Nurses' Health Study, who provided blood samples in 1989 to 1990. Cases
      and controls were individually matched on year of birth, time period of and
      indication(s) for endoscopy, and date of blood draw. RESULTS: High concentrations
      of C-peptide, an indicator of insulin secretion, were statistically significantly
      associated with risk of distal colorectal adenoma [multivariable relative risk
      (MVRR) top versus bottom quartile, 1.63; 95% confidence interval (95% CI), 1.01
      2.66; P = 0.01], even after including body mass index and physical activity in
      the statistical model. Fasting IGF binding protein-1 (IGFBP-1) concentrations did
      not show any clear association with risk for adenoma (MVRR top versus bottom
      quartile, 1.08; 95% CI, 0.56-2.07). These associations did not differ
      significantly by size/stage of adenoma. Glycosylated hemoglobin (HbA1c) was
      associated with a nonstatistically significant increased risk of colorectal
      adenoma (MVRR top versus bottom quartile, 1.47; 95% CI, 0.89-2.44). CONCLUSIONS:
      High HbA1c and low IGFBP-1 were not clearly associated with increased risk of
      distal colorectal adenoma. However, our current results and previous associations
      between C-peptide and colorectal cancer suggest that hyperinsulinemia may play a
      role throughout the development of colorectal neoplasia.

PMID- 16614120
TI  - Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation
      genes, interactions with smoking and prostate cancer risk.
AB  - The relationship between cigarette smoking and prostate cancer remains unclear.
      Any potential association may depend on the individuals' ability to metabolize
      and detoxify cigarette carcinogens--such as polycyclic aromatic hydrocarbons. To
      investigate this, we studied the association between prostate cancer and smoking,
      as well as the main and modifying effects of functional polymorphisms in genes
      that metabolize polycyclic aromatic hydrocarbons (CYP1A1 Ile(462)Val, microsomal
      epoxide hydrolase His(139)Arg) and detoxify reactive derivatives (GSTM1 null
      deletion, GSTT1 null deletion, GSTP1 Ile(105)Val and Ala(114)Val) using a family
      based case-control design (439 prostate cancer cases and 479 brother controls).
      Within the entire study population, there were no main effects for smoking or any
      of the polymorphisms. However, the nondeleted GSTM1 allele was inversely
      associated with prostate cancer [odds ratio (OR), 0.50; 95% confidence interval
      (95% CI), 0.26-0.94] among men with less aggressive disease (Gleason score < 7
      and clinical tumor stage < T2c) and positively associated (OR, 1.68; 95% CI, 1.01
      2.79) with prostate cancer in men with more aggressive disease (Gleason score >
      or = 7 or clinical tumor stage > or = T2c). We also found a statistically
      significant negative multiplicative interaction between the GSTM1 nondeleted
      allele and heavy smoking (> 20 pack-years) in the total study population (P =
      0.01) and in Caucasians (P = 0.01). Among Caucasians, heavy smoking increased
      prostate cancer risk nearly 2-fold in those with the GSTM1 null genotype (OR,
      1.73; 95% CI, 0.99-3.05) but this increased risk was not observed in heavy
      smokers who carried the GSTM1 nondeleted allele (OR, 0.95; 95% CI, 0.53-1.71).
      Our results highlight the importance of considering genetic modifiers of
      carcinogens when evaluating smoking in prostate cancer.

PMID- 16614121
TI  - Polymorphisms in the hMSH2 gene and the risk of primary lung cancer.
AB  - Polymorphisms in the DNA repair genes may be associated with differences in the
      capacity to repair DNA damage, and so this can influence an individual's
      susceptibility to lung cancer. To test this hypothesis, we investigated the
      association of hMSH2 -118T>C, IVS1+9G>C, IVS10+12A>G, and IVS12-6T>C genotypes
      and their haplotypes with the risk of lung cancer in a Korean population. The
      hMSH2 genotypes were determined in 432 lung cancer patients and in 432 healthy
      controls who were frequency matched for age and gender. The hMSH2 haplotypes were
      estimated based on a Bayesian algorithm using the Phase program. The presence of
      at least one IVS10+12G allele was associated with a significantly decreased risk
      of adenocarcinoma, as compared with the IVS10+12AA genotype [adjusted odds ratio
      (OR), 0.59; 95% confidence interval (95% CI), 0.40-0.88; P = 0.01], and the
      presence of at least one IVS12-6C allele was associated with a significantly
      increased risk of adenocarcinoma, as compared with the IVS12-6TT genotype
      (adjusted OR, 1.52; 95% CI, 1.02-2.27; P = 0.04). Consistent with the results of
      the genotyping analysis, the TGGT haplotype with no risk allele was associated
      with a significantly decreased risk of adenocarcinoma, as compared with the TCAC
      haplotype with two risk allele [i.e., IVS10+12A and IVS12-6C allele; adjusted OR,
      0.49; 95% CI, 0.30-0.78; P = 0.003 and P(c) (Bonferroni corrected P value) =
      0.012]. The effect of the hMSH2 haplotypes on the risk of adenocarcinoma was
      statistically significant in the never smokers and younger individuals (adjusted
      OR, 0.45; 95% CI, 0.27-0.75; P = 0.002 and P(c) = 0.004; and adjusted OR, 0.44;
      95% CI, 0.23-0.85; P = 0.014 and P(c) = 0.028, respectively) but not in the ever
      smokers and older individuals. These results suggest that the hMSH2 polymorphisms
      and their haplotypes may be an important genetic determinant of adenocarcinoma of
      the lung, particularly in never smokers.

PMID- 16614122
TI  - The effect of medicare health care delivery systems on survival for patients with
      breast and colorectal cancer.
AB  - BACKGROUND: Two of the most common types of health care delivery systems in the
      U.S. are fee-for-service (FFS) and managed care systems such as health
      maintenance organizations (HMO). Differences may exist in patient outcomes
      depending on the health care delivery system in which they are enrolled. We
      evaluated differences in the survival of patients with breast and colorectal
      cancer at diagnosis between the two Medicare health care delivery systems (FFS
      and HMO). METHODS: We used a linkage of two national databases, the Medicare
      database from the Centers for Medicare and Medicaid Services, and the National
      Cancer Institute's Surveillance, Epidemiology, and End Results program database,
      to evaluate differences in demographic data, stage at diagnosis, and survival
      between breast and colorectal cancer over the period 1985 to 2001. RESULTS:
      Medicare patients enrolled in HMOs were diagnosed at an earlier stage of
      diagnosis than FFS patients. HMO patients diagnosed with breast and colorectal
      cancer had improved survival, and these differences remained even after
      controlling for potential confounders (such as stage at diagnosis, age, race,
      socioeconomic status, and marital status). Specifically, patients enrolled in
      HMOs had 9% greater survival in hazards ratio if they had breast cancer, and 6%
      if they had colorectal cancer. CONCLUSIONS: Differences exist in survival among
      patients in HMOs compared with FFS. This is likely due to a combination of
      factors, including but not limited to, earlier stage at the time of diagnoses.

PMID- 16614123
TI  - Prospective study of alcohol consumption and risk of oral premalignant lesions in
      men.
AB  - Recent case-control studies indicate that alcohol increases the risk of oral
      premalignant lesions (OPL) among tobacco users, but the independent association
      between alcohol and OPL remains unclear. We prospectively evaluated the
      association between alcohol consumption and the incidence of OPL. Participants
      were 41,458 men in the Health Professionals Follow-up Study. Alcohol consumption
      was assessed every 4 years using validated food frequency questionnaires. We
      confirmed clinically or histopathologically diagnosed OPL events occurring
      between 1986 and 2002 by medical record review (193 cases). Multivariate-adjusted
      relative risks of OPL were calculated from Cox proportional hazards models. With
      detailed control for tobacco and other variables, multivariate relative risks
      (95% confidence intervals) were 1.7 (0.9-3.2) for drinkers of 0.1 to 14.9 g/d,
      2.9 (1.5-5.6) for 15 to 29.9 g/d, and 2.5 (1.3-5.1) for > or =30 g/d, compared
      with nondrinkers. Approximately one additional drink per day (12.5 g) was
      associated with a 22% increase in risk (P < 0.001). The associations did not vary
      by beverage type, frequency, or consumption with meals. Results were similar when
      restricted to cases of oral epithelial dysplasia. Alcohol increased OPL risk in
      never-users of tobacco as well as in past or current users. An interaction
      between alcohol and tobacco was apparent by their more-than-additive joint
      effects. Alcohol is an independent risk factor for OPL, regardless of beverage
      type or drinking pattern. Recommendations to reduce alcohol intake have the
      potential to reduce incidence of OPL in nonsmokers and smokers alike.

PMID- 16614124
TI  - Are there gender differences in colorectal cancer test use prevalence and
      correlates?
AB  - Despite evidence that screening tests reduce colorectal cancer incidence and
      mortality, screening prevalence is low. Gender differences in test uptake have
      been reported, but few studies examine correlates of test use by gender.
      Differences, if present, may inform strategies to increase test use. We examined
      gender differences in the prevalence and correlates of colorectal cancer test use
      [fecal occult blood test (FOBT) and endoscopy] using data from the 2002 to 2003
      Health Information National Trends Survey. Male (n = 999) and female (n = 1687)
      respondents ages > or =50 years, without a personal history of colorectal cancer,
      were interviewed by telephone. Age-adjusted prevalence rates were reported for
      lifetime, recent, and repeat use by gender and test type. Multivariable logistic
      regression analyses were used to identify correlates of test use stratified by
      gender and colorectal cancer test type. More females reported only using FOBT in
      lifetime and in the past year, whereas more males reported repeat endoscopy use.
      The use of other tests or combinations of tests did not differ by gender.
      Consistent positive correlates of colorectal cancer test use for both genders
      included age, recent physician visits, recent breast or prostate cancer
      screening, and knowledge of test-specific screening intervals. Correlates that
      differed by gender included comparative perceived risk, belief that colorectal
      cancer testing was too expensive, fear of finding colorectal cancer if tested,
      and attention to and trust in media sources of health information. Such
      differences, if confirmed in future studies, may inform the use of gender
      specific intervention strategies or messages to increase colorectal cancer test
      use.

PMID- 16614125
TI  - Emerging and widening colorectal carcinoma disparities between Blacks and Whites
      in the United States (1975-2002).
AB  - BACKGROUND: Colorectal carcinoma (CRC) is the fourth most common cancer diagnosed
      and the second most common cause of cancer death in the U.S. Incidence and
      mortality rates have decreased since the mid-1980s, although more among Whites
      than Blacks. METHODS: To determine if these racial differences were changing over
      time, we examined CRC rates in the National Cancer Institute's Surveillance,
      Epidemiology, and End Results (SEER) program (1975-2002). Rates were stratified
      by gender, race, anatomic subsite, historic stage, and grade. RESULTS: CRC rates
      were higher among men than women and higher among Blacks than Whites, with Black
      men having the highest rates during the latter years. Prior to the mid-1980s,
      male CRC rates were actually higher among Whites than Blacks; after which there
      was ethnic crossover with Black rates higher than White rates, and the gaps are
      widening. Proximal and transverse CRCs were more common and rectal cancers were
      less common among Blacks than Whites. Over time, rates for localized and regional
      stages increased among Blacks and decreased among Whites. Rates for distant
      stages declined for both racial groups, although less among Blacks. Black-to
      White rate ratio for distant stage was approximately 1.30. Notably, Blacks
      compared with Whites had lower grade tumors, despite higher stages and mortality
      rates. CONCLUSIONS: CRC racial disparities have emerged and widened for three
      decades. These temporal trends probably reflect complicated racial differences
      between screening practice patterns and etiologic factors.

PMID- 16614126
TI  - Smoking and overweight: negative prognostic factors in stage III epithelial
      ovarian cancer.
AB  - OBJECTIVE: Smoking and overweight are associated with poorer prognosis in several
      cancer types. The prognostic effect of smoking and body mass index (BMI) on
      ovarian cancer is unknown. METHODS: Ovarian cancer cases were from the Danish
      MALOVA (MALignant OVArian cancer) study. Information on smoking status and BMI
      was obtained from a personal interview conducted closely after primary surgery.
      Cox regression models were used to estimate adjusted hazard ratios (HR) and 95%
      confidence intervals (95% CI) for ovarian cancer-specific death in relation to
      smoking variables and BMI. RESULTS: A total of 295 women with stage III
      epithelial ovarian cancer were identified and followed to death or for a median
      of 7.3 years (range, 5.4-9.5 years). Median survival time for normal-weight never
      smokers was 2.8 years (95% CI, 2.3-3.2) compared with 1.2 years (95% CI, 0.8-2.3)
      for overweight current smokers. Current smokers had a significantly increased
      risk of ovarian cancer death compared with never smokers in multivariate Cox
      analysis (HR, 1.65; 95% CI, 1.22-2.24). The negative effect of smoking diminished
      with increasing time since a former smoker had stopped smoking (HR, 0.89; 95% CI,
      0.80-0.98 per 5 years since stop of smoking). Overweight women also had an
      increased risk of ovarian cancer death (HR, 1.83; 95% CI, 1.38-2.42) compared
      with normal-weight women. CONCLUSION: Smoking at the time of diagnosis and
      premorbid overweight were negative prognostic factors for ovarian cancer-specific
      survival. The negative effect of smoking decreased with increasing time since
      stop of smoking.

PMID- 16614127
TI  - Effects of chemical form of selenium on plasma biomarkers in a high-dose human
      supplementation trial.
AB  - Intervention trials with different forms of selenium are under way to assess the
      effects of selenium supplements on the incidence of cancer and other diseases.
      Plasma selenium biomarkers respond to selenium administration and might be useful
      for assessing compliance and safety in these trials. The present study
      characterized the effects of selenium supplementation on plasma selenium
      biomarkers and urinary selenium excretion in selenium-replete subjects. Moderate
      (approximately 200 microg/d) to large (approximately 600 microg/d) selenium
      supplements in the forms sodium selenite, high-selenium yeast (yeast), and l
      selenomethionine (selenomethionine) were administered. Subjects were randomized
      into 10 groups (placebo and three dose levels of each form of selenium). Plasma
      biomarkers (selenium concentration, selenoprotein P concentration, and
      glutathione peroxidase activity) were determined before supplementation and every
      4 weeks for 16 weeks. Urinary selenium excretion was determined at 16 weeks.
      Supplementation with selenomethionine and yeast raised the plasma selenium
      concentration in a dose-dependent manner. Selenite did not. The increased
      selenium concentration correlated with the amount of selenomethionine
      administered. Neither glutathione peroxidase activity nor selenoprotein P
      concentration responded to selenium supplementation. Urinary selenium excretion
      was greater after selenomethionine than after selenite, with excretion after
      yeast being intermediate and not significantly different from either of the other
      two. We conclude that plasma selenium concentration is useful in monitoring
      compliance and safety of selenium supplementation as selenomethionine but not as
      selenite. Plasma selenium seems to reflect the selenomethionine content of yeast
      but not the other yeast selenium forms. As judged by urinary selenium excretion,
      selenium in the form of selenomethionine is better absorbed than selenite.

PMID- 16614128
TI  - OGG1 polymorphisms and breast cancer risk.
AB  - The role of oxidative stress in breast cancer risk is still unclear. OGG1 encodes
      an 8-oxoguanine DNA glycosylase/AP lyase that catalyzes the removal of 8
      oxodeoxyguanosine from DNA. 8-Oxodeoxyguanosine, the most abundant lesion
      generated by oxidative stress, is highly mutagenic. Environmental sources of
      oxidative stress, such as alcohol consumption, cigarette smoking, high body mass
      index (BMI), and low fruits and vegetables intake, may modify the association of
      genetic polymorphisms with breast cancer risk. We investigated the association
      between three genetic polymorphisms in OGG1 (Ser(326)Cys, 7143A/G, and 11657A/G)
      and breast cancer risk among 1,058 cases and 1,102 controls participating in the
      Long Island Breast Cancer Study Project. No associations were observed between
      individual OGG1 polymorphisms, haplotypes, or diplotypes and breast cancer. The
      association between having at least one variant allele and breast cancer risk was
      stronger among moderate alcohol drinkers for Ser(326)Cys [odds ratio (OR), 1.82;
      95% confidence interval (95% CI), 1.06-3.10] relative to nondrinkers with the
      wild-type genotype and among those with higher BMI for 7143A/G (OR, 1.47; 95% CI,
      1.10-1.96) and for 11657A/G (OR, 1.41; 95% CI, 1.05-1.88), relative to women with
      BMI < 25 kg/m(2) and the wild-type genotype. However, the patterns were not seen
      for all three single nucleotide polymorphisms (SNP) nor were there any clear
      allele dose associations; only one interaction was statistically significant,
      assuming a multiplicative model (11657A/G, P(interaction) = 0.04). In summary,
      although we found some differences between the three OGG1 SNPs and breast cancer
      risk among moderate alcohol drinkers and women with higher BMI, replication of
      these results is needed to rule out spurious findings. In addition, data on
      functionality of these polymorphisms are crucial to understand if these modest
      differences are important.

PMID- 16614129
TI  - Buccal DNA collection: comparison of buccal swabs with FTA cards.
AB  - Collection and analysis of DNA, most commonly from blood or buccal cells, is
      becoming more common in epidemiologic studies. Buccal samples, which are painless
      to take and relatively easily collected, are often the preferred source. There
      are several buccal cell collection methods: swabs, brushes, mouthwash, and
      treated cards, such as FTA or IsoCode cards. Few studies have systematically
      compared methods of buccal cell collection with respect to DNA yield and
      amplification success under similar conditions. We compared buccal DNA collection
      and amplification using buccal swabs and FTA cards in 122 control subjects from
      our Australian case-control study of childhood acute lymphoblastic leukaemia.
      Buccal DNA was quantified using a real-time PCR for beta-actin and genotyped at
      the loci of three polymorphisms (MTHFR 677C>T, ACE I/D, and XPD 1012G>A). PCR was
      successful with DNA from buccal swabs for 62% to 89% of subjects and from FTA
      cards for 83% to 100% of subjects, depending on the locus. The matched pair odds
      ratios (95% confidence interval) comparing success of FTA cards with buccal swabs
      are as follows: MTHFR 677C>T using PCR-RFLP, 12.5 (11.6-13.5) and using real-time
      PCR, 130.0 (113.1-152.8); ACE I/D using PCR-amplified fragment length
      polymorphism, 3.36 (3.2-3.5); XPD 1012G>A using real-time PCR, 150.0 (132.7
      172.3). FTA cards are a robust DNA collection method and generally produce DNA
      suitable for PCR more reliably than buccal swabs. There are, however, technical
      challenges in handling discs punched from FTA cards that intending users should
      be aware of.

PMID- 16614130
TI  - Increased risk for cervical disease progression of French women infected with the
      human papillomavirus type 16 E6-350G variant.
AB  - To test the significance of human papillomavirus (HPV) type 16 and HPV16 E6
      variants as risk factors for viral persistence and progression to high-grade
      lesion, we did a nested case-control study within a cohort study of >15,000
      Caucasian French women. Three groups infected with high-risk HPV were compared:
      (a) women with cleared infection (controls, n = 201), (b) women with persistent
      infection (cases, n = 87), and (c) women who progressed into high-grade lesion
      (cases, n = 58). Women with persistent HPV infection and those that progressed
      into high-grade lesions were likelier to harbor HPV16 than other high-risk HPV
      types [odds ratio (OR), 2.4; 95% confidence interval (95% CI), 1.3-4.3 and OR,
      4.2; 95% CI, 2.2-8.1, respectively]. Notably, especially elevated ORs of
      persistence (3.0; 95% CI, 1.4-6.7) and progression (6.2; 95% CI, 2.7-14.3) were
      found among women who harbored the HPV16 350G variant. Thus, HPV type and HPV16
      variant seem to be risk factors for viral persistence and progression of
      infections into high-grade cervical lesions.

PMID- 16614131
TI  - Quantitative comparison of aflatoxin B1 serum albumin adducts in humans by
      isotope dilution mass spectrometry and ELISA.
AB  - Metabolic activation of the hepatocarcinogenic mycotoxin aflatoxin B(1) (AFB(1))
      results in the covalent attachment of AFB(1) to serum albumin. Digestion of
      adducted albumin releases AFB(1)-lysine, a biomarker of exposure status. AF
      albumin adducts have been most frequently measured in precipitated serum albumin
      using an immunoassay (ELISA); however, a sensitive and specific isotope dilution
      mass spectrometric (IDMS) assay for measurement of AFB(1)-lysine in serum has
      recently been developed. The ELISA and IDMS methods were compared using 20 human
      sera collected in Guinea, West Africa, where AF exposure is endemic. Measurement
      of AFB(1)-lysine adduct concentrations by IDMS in serum and albumin precipitated
      from the same sample revealed that precipitation has no effect on the measured
      adduct levels. The concentration of AF-albumin adducts measured by ELISA and
      AFB(1)-lysine measured by IDMS in 2 mg of albumin were well correlated (R = 0.88,
      P < 0.0001); however, AF-albumin adduct concentrations measured by ELISA were on
      average 2.6-fold greater than those of the AFB(1)-lysine adduct. Although these
      data suggest that the ELISA is measuring other AF adducts in addition to AFB(1)
      lysine, these biomarkers are comparable in their ability to assess AF exposure at
      AF-albumin concentrations > or =3 pg AFB(1)-lysine equivalents/mg albumin.
      Identification of other adducts may clarify the mechanistic basis for using AF
      protein biomarkers to assess exposure status in future epidemiologic studies of
      liver cancer.

PMID- 16614132
TI  - Independent occurrences of multiple repeats in the control region of
      mitochondrial DNA of white-tailed deer.
AB  - Deer in the genera Mazama and Odocoileus generally have two copies of a 75-base
      pair (bp) repeat in the left domain of the control region of the mitochondrial
      DNA (mtDNA). Phylogenetic analyses further suggest an ancient origin for the
      duplication supporting a previously stated contention that this event occurred
      before the separation of Mazama and Odocoileus. However, white-tailed deer
      (Odocoileus virginianus) had three or four copies of a 75-bp repeat in the
      control region of their mtDNA in 7.8% of the individuals analyzed, and all of
      these animals were from the coastal plain of the southeastern United States. When
      copy 3 is present, it is very similar in sequence to copy 2, but variation
      suggests that copy 3 probably evolved multiple times from copy 2. The pattern of
      phylogenetic clustering of the haplotypes from across the coastal plain also
      suggests that phenotypes with three or four copies of the repeat have originated
      multiple times. The 44 observed haplotypes showed strong spatial subdivision
      across the area with subpopulations frequently showing complete shifts in
      haplotype frequencies from others taken from nearby areas. Many of the
      subpopulations right along the coast or on adjacent barrier islands have a
      limited number of haplotypes as would occur in populations undergoing drift
      because of small numbers of breeding females and limited female dispersal.

PMID- 16614133
TI  - High levels of genetic variation exist in Aspergillus niger populations infecting
      Welwitschia mirabilis hook.
AB  - Aspergillus niger is an asexual, haploid fungus which infects the seeds of
      Namibia's national plant, Welwitschia mirabilis, severely affecting plant
      viability. We used 31 randomly amplified polymorphic DNA markers to assess
      genetic variation among 89 A. niger isolates collected from three W. mirabilis
      populations in the Namib Desert. While all isolates belonged to the same
      vegetative compatibility group, 84% were unique genotypes, and estimates of
      genotypic evenness and Simpson's index of diversity approached 1.0 in the three
      populations. Analysis of molecular variance revealed that 78% of the total
      variation sampled was among isolates from individual W. mirabilis plants. Lower,
      but significant, amounts of variation detected among isolates from different
      plants (12%) and different sites (10%) also indicated some site- and plant-level
      genetic differentiation. Total gene diversity (H(T) = 0.264) was mostly
      attributable to diversity within populations (H(S) = 0.217); the relatively low
      level of genetic differentiation among the sites (G(ST) = 0.141) suggests that
      gene flow is occurring among the three distant sites. Although sexual
      reproduction has never been observed in this fungus, parasexuality is a well
      known phenomenon in laboratory strains. We thus attribute the high levels of
      genetic variation to parasexuality and/or wind-facilitated gene flow from an as
      of yet undocumented broader host range of the fungus on other desert vegetation.
      Given the apparent ease of transmission, high levels of genetic diversity, and
      potentially broad host range, A. niger infections of W. mirabilis may be
      extremely difficult to control or prevent.

PMID- 16614134
TI  - Source populations of Quercus glauca in the last glacial age in Taiwan revealed
      by nuclear microsatellite markers.
AB  - In this work, we attempted to study genetic differentiation between populations
      of Quercus glauca in Taiwan using nuclear microsatellite markers to infer the
      potential refugium in the last glaciation stage. Four microsatellite loci for 20
      individuals each in 10 populations of Taiwan were analyzed. We found that Q.
      glauca has relatively high within-population diversity (H(E) = 0.741) and low
      population differentiation (F(ST) = 0.042) but shows isolation by distance. The
      most divergent populations, according to the average F(ST) for individual
      populations in comparison with every other population, were found in populations
      Cy, Sa, and Hy in southern Taiwan and Pa in north-central Taiwan. Moreover,
      populations Cy, Sa, and Pa were recognized as being the source populations for
      gene recolonization after the last glaciation stage. In addition, the three sites
      of Wu, Ym, and Cy exhibited the highest gene diversities that coincided with
      populations with the highest chloroplast DNA variations. This may have resulted
      from an admixture of colonization routes. In conclusion, observations of the most
      divergent populations and source populations suggest that southern and probably
      north-central Taiwan may have potentially been refugia for Q. glauca in the last
      glaciation. This agrees with the possible refugium in southern Taiwan revealed by
      a previous study using chloroplast DNA markers.

PMID- 16614135
TI  - Electrophoretic evidence for disomic inheritance and allopolyploid origin of the
      octoploid Cerastium alpinum (Caryophyllaceae).
AB  - The mode of inheritance of six enzyme markers in the octoploid alpine plant
      Cerastium alpinum was analyzed. Offspring from crosses between heterozygotes
      showed fixed heterozygosity at malate dehydrogenase-2, phosphoglucoisomerase-2,
      triosephosphate isomerase-2, and triosephosphate isomerase-3. Phosphoglucomutase
      1 also showed fixed heterozygosity except in offspring from one cross. Fixed
      heterozygosity in five enzyme systems suggests that C. alpinum has originated
      through at least some allopolyploidization. Offspring from plants heterozygous
      for two alleles at the menadione reductase-1 (Mr-1) locus did not deviate
      significantly from a 1:2:1 ratio. The large proportion of homozygotes suggests
      disomic inheritance because any kind of polysomic inheritance would result in a
      substantially increased proportion of heterozygotes relative to disomic
      inheritance. Assuming a diploid model for Mr-1, this locus was used to analyze
      the population genetic structure within C. alpinum populations. Inbreeding was
      found in many alpine populations. This may help explain the large genetic
      distances found among alpine populations in a previous study. The analysis is
      only based on one segregating locus, and the results should therefore be treated
      with caution. However, by establishing the mode of inheritance through crosses,
      we have been able to use a codominant marker in population genetic analysis of an
      octoploid plant.

PMID- 16614136
TI  - Inheritance of gynoecism in bitter gourd (Momordica charantia L.).
AB  - The inheritance of sex expression in cucumber (Cucumis sativus) and other
      cucurbits is well documented; however, the genetics of female sex (gynoecism)
      expression in bitter gourd (Momordica charantia) has not been described.
      Inheritance of gynoecism in bitter gourd was studied in a 100% gynoecious line
      (Gy263B). The F(2) and testcross segregation data revealed that gynoecism in
      Gy263B is under the control of a single, recessive gene. Following the gene
      nomenclature of cucurbits, it is proposed that the gene symbol, gy-1, be assigned
      for the expression of gynoecism in bitter gourd.

PMID- 16614137
TI  - Validation of a handheld display device for an expandable labeled magnitude scale
      (LMS).
AB  - Palmtop computers provide a possible avenue for the convenient collection of
      subjective ratings from individuals outside of a fixed laboratory setting. One
      disadvantage of these computers is the small size of their display screens, which
      may reduce the resolution of responses available as compared with standard
      display screens. One plausible solution to this problem is to use a scale that
      expands contingent on an initial response made by the subject, so that the final
      response is made from a scale with finer resolution. To validate this approach,
      we compared taste intensity judgments of six sucrose solutions (0.03, 0.06, 0.12,
      0.24, 0.48, and 0.96 M), using a labeled magnitude scale either presented in
      expandable form on a palmtop computer (Palm scale) or in conventional
      (nonexpandable) form on a standard 17'' PC monitor (PC scale). Twenty-four
      subjects rated all six sucrose solutions thrice, using both scale types, the
      different scales being used on different days of testing. The scales led to very
      similar taste intensity ratings at all but the lowest concentration, which was
      rated less intense on the Palm scale. The Palm scale was used with slightly less
      precision than the PC scale for the weakest solution concentrations. In summary,
      the responses of the two scales were similar enough to validate the use of the
      expandable scale on the palmtop computer outside the laboratory setting.

PMID- 16614139
TI  - Reducing and oxidizing agents sensitize heat-activated vanilloid receptor (TRPV1)
      current.
AB  - We have previously reported that the reducing agent dithiothreitol (DTT) strongly
      increases thermally induced activity of the transient receptor potential
      vanilloid receptor-1 (TRPV1) channel. Here, we show that exposure to oxidizing
      agents also enhances the heat-induced activation of TRPV1. The actions of
      sulfhydryl modifiers on heat-evoked whole-cell membrane currents were examined in
      TRPV1-transfected human embryonic kidney 293T cells. The sensitizing effects of
      the membrane-permeable oxidizing agents diamide (1 mM), chloramine-T (1 mM), and
      the copper-o-complex (100:400 microM) were not reversed by washout, consistent
      with the stable nature of covalently modified sulfhydryl groups. In contrast, the
      membrane-impermeable cysteine-specific oxidant 5,5'-dithio-bis-(2-nitrobenzoic
      acid) (0.5 mM) was ineffective. The alkylating agent N-ethylmaleimide (1 mM)
      strongly and irreversibly affected heat-evoked responses in a manner that
      depended on DTT pretreatment. Extracellular application of the membrane
      impermeable reducing agent glutathione (10 mM) mimicked the effects of 10 mM DTT
      in potentiating the heat-induced and voltage-induced membrane currents. Using
      site-directed mutagenesis, we identified Cys621 as the residue responsible for
      the extracellular modulation of TRPV1 by reducing agents. These data suggest that
      the vanilloid receptor is targeted by redox-active substances that directly
      modulate channel activity at sites located extracellularly as well as within the
      cytoplasmic domains. The results obtained demonstrate that an optimal redox state
      is crucial for the proper functioning of the TRPV1 channel and both its reduced
      and oxidized states can result in an increase in responsiveness to thermal
      stimuli.

PMID- 16614138
TI  - Neuroprotective effects of 17beta-estradiol and nonfeminizing estrogens against
      H2O2 toxicity in human neuroblastoma SK-N-SH cells.
AB  - Neuroprotective effects of estrogens have been shown in various in vitro and in
      vivo models, but the mechanisms underlying protection by estrogen are not clear.
      Mounting evidence suggests antioxidant effects contribute to the neuroprotective
      effects of estrogens. In the present study, we assessed the protective effects of
      estrogens against H2O2-induced toxicity in human neuroblastoma cells and the
      potential mechanisms involved in this protection. We demonstrate that 17beta
      estradiol (17beta-E2) increases cell survival against H2O2 toxicity in human
      neuroblastoma cells. 17beta-E2 effectively reduced lipid peroxidation induced by
      5-min H2O2 exposure. Furthermore, 17beta-E2 exerts the protective effects by
      maintaining intracellular Ca2+ homeostasis, attenuating ATP depletion, ablating
      mitochondrial calcium overloading, and preserving mitochondrial membrane
      potential. Two nonfeminizing estrogens, 17alpha- and ent-estradiol, were as
      effective as 17beta-E2 in increasing cell survival, alleviating lipid
      peroxidation, preserving mitochondrial function, and maintaining intracellular
      glutathione levels and Ca2+ homeostasis against H2O2 insult. Moreover, the
      estrogen receptor antagonist fulvestrant (ICI 182,780) did not block effects of
      17beta-E2, but increased cell survival and blunted intracellular Ca2+ increases.
      However, these estrogens failed to reduce cytosolic reactive oxygen species, even
      at concentrations as high as 10 microM. In conclusion, estrogens exert protective
      effects against oxidative stress by inhibiting lipid peroxidation and
      subsequently preserving Ca2+ homeostasis, mitochondrial membrane potential, and
      ATP levels.

PMID- 16614140
TI  - Resveratrol suppresses tumor necrosis factor-alpha-induced fractalkine expression
      in endothelial cells.
AB  - Up-regulation of fractalkine is involved in vascular and tissue damage in
      inflammatory conditions. Resveratrol has been shown to have anti-inflammatory,
      antioxidant, and antitumor activities. Its regulatory effects on expression of
      fractalkine in vascular endothelial cells and fractalkine receptor CX3CR1 in
      monocytes have not been studied. We evaluated the effects of resveratrol on
      fractalkine expression in human umbilical vein endothelial cells and CX3CR1
      expression in THP-1 cells in response to treatment with tumor necrosis factor
      (TNF)-alpha. TNF-alpha significantly induced fractalkine mRNA and protein
      expression in endothelial cells. Resveratrol strongly suppressed TNF-alpha
      induced fractalkine expression in endothelial cells through suppression of
      nuclear factor-kappaB and Sp1 activities. Resveratrol decreased the number of TNF
      alpha-induced fractalkine-positive endothelial cells and CX3CR1-positive cells
      determined by flow cytometric analysis. Resveratrol suppressed TNF-alpha
      stimulated monocytes adhesion to human umbilical vein endothelial cells.
      Immunohistochemical analysis revealed that resveratrol suppressed TNF-alpha
      induced arterial endothelial fractalkine expression in heart, kidney, and
      intestine and decreased ED-1-positive cell infiltration in intestinal villi.
      Resveratrol may provide a new pharmacological approach for suppressing
      fractalkine/CX3CR1-mediated injury in inflammatory conditions.

PMID- 16614141
TI  - Update on anticoagulant medications for the interventional radiologist.
AB  - For many years, available anticoagulant medications were limited to vitamin K
      antagonists, unfractionated heparin, and aspirin. However, in the past 20 years,
      several new agents have been developed for the treatment of thrombosis, and even
      more are being developed. This increasing number of medications has led to more
      specific treatment algorithms for the care of venous and arterial thrombotic
      events. As more agents become available, treatment guidelines are rapidly
      changing. With increasing frequency, interventional radiologists encounter
      patients already taking anticoagulant medications prophylactically or
      therapeutically, or they need to determine which anticoagulant medications need
      to be initiated for a particular procedure. Therefore, it has become increasingly
      important to understand the mechanisms, risks, and benefits of anticoagulant
      medications. A review of the traditional anticoagulants, their new counterparts,
      and their places in the medication repertoire of interventional radiology will be
      discussed herein.

PMID- 16614142
TI  - Society of Interventional Radiology position statement: treatment of acute
      iliofemoral deep vein thrombosis with use of adjunctive catheter-directed
      intrathrombus thrombolysis.

PMID- 16614143
TI  - Clinical competence statement on thoracic endovascular aortic repair (TEVAR)-
      multispecialty consensus recommendations: a report of the SVS/SIR/SCAI/SVMB
      writing committee to develop a clinical competence standard for TEVAR.

PMID- 16614144
TI  - Angioplasty balloon inflation pressures during treatment of hemodialysis graft
      related stenoses.
AB  - PURPOSE: This two-part prospective investigation was designed to determine the
      balloon inflation pressures required to dilate stenoses associated with
      hemodialysis grafts and evaluate the burst pressures of five different
      angioplasty balloons. MATERIALS AND METHODS: Eighty-nine patients with
      dysfunctional hemodialysis grafts were enrolled and underwent fistulography. The
      diagnostic studies revealed 104 stenoses, which were treated with balloon
      angioplasty. The characteristics of these stenoses and the balloon inflation
      pressures required to dilate the lesions were recorded. In part two of this
      investigation, the burst pressures of five different angioplasty balloons were
      evaluated immediately after their use during angioplasty procedures. Twenty-five
      balloons of each type were inflated until the balloon burst or 30 atm of pressure
      was achieved. Several different statistical tests were used to analyze the data
      set. RESULTS: The mean balloon inflation pressure required to dilate all 104
      stenoses was 17.2 atm. Subgroup analysis revealed that the mean balloon inflation
      pressure required to dilate 75 venous anastomotic stenoses was 17.9 atm and that
      a mean pressure of 15.6 atm was required to dilate 29 stenoses located within the
      native outflow veins. The angioplasty balloon burst pressure experiments revealed
      that the majority of the tested balloons can be inflated to pressures 5-6 atm
      greater than the manufacturers' rated burst pressures. However, the margin of
      safety for overinflation was variable among the balloons tested, and angioplasty
      balloons experience fatigue with repeated inflations. CONCLUSION: The majority of
      stenoses associated with hemodialysis grafts can be successfully dilated with use
      of available high-pressure angioplasty balloons.

PMID- 16614145
TI  - Tenecteplase in acute lower-leg ischemia: efficacy, dose, and adverse events.
AB  - PURPOSE: To prospectively evaluate tenecteplase (TNK) for thrombolysis in acute
      lower-limb ischemia. MATERIALS AND METHODS: Forty-three consecutive limbs in 37
      patients (15 male, 22 female) were treated for acute lower-limb ischemia. Group 1
      included 22 limbs treated with TNK infusion of 0.25 mg/h and group 2 included 21
      limbs treated with TNK at 0.125 mg/h. Technical success was defined by 95%
      clearing of thrombus, and clinical success was defined by Society of
      Interventional Radiology category for acute ischemia of +1. Complications were
      ranked by severity and relation to TNK administration. Logistic regression,
      Student t test, and analysis of variance were performed. RESULTS: TNK infusions
      averaged 24 hours in duration (SD, 13 h), with means of 20 hours in group 1 and
      27 hours in group 2 (P = .071). Technical success was achieved in 84% of limbs
      (36 of 43): 82% in group 1 (18 of 22) and 86% in group 2 (18 of 21; P = .827).
      The SIR ischemia category improved (ie, +1) in 86% of limbs (37 of 43), stayed
      the same (ie, category 0) in 12% of limbs (five of 43), and worsened (ie, -1) in
      2% of limbs (one of 43). TNK-related complications were seen in 12% of limbs (n =
      5) and were correlated with percentage decrease in fibrinogen level, initial TNK
      bolus, and abciximab administration (P = .001, P < .001, and P = .036,
      respectively). Initial TNK boluses of 1.5 mg or less were associated with fewer
      complications than boluses of 3-5 mg (P = .045). The percentage decrease in
      fibrinogen level in group 1 was 23% (SD, 29%), compared with 7% in group 2 (SD,
      20%; P = .045). There was a 7% incidence of major bleeding complications (n = 3)
      and no intracranial hemorrhages. CONCLUSIONS: Treatment of acute lower-limb
      ischemia with TNK infusion at 0.25 mg/h and 0.125 mg/h is associated with similar
      success and complication rates. TNK-related complications correlated with initial
      TNK bolus, abciximab treatment, and percent decrease in fibrinogen level. The
      initial TNK bolus dose should be limited to 1.5 mg.

PMID- 16614146
TI  - Stent placement with the monorail technique for treatment of mesenteric artery
      stenosis.
AB  - PURPOSE: To analyze the immediate and midterm success of stenting of mesenteric
      arteries by a monorail technique in patients with chronic mesenteric ischemia.
      MATERIALS AND METHODS: In this prospective case series, 19 patients (11 male, 8
      female; mean age, 62.9 +/- 10.4 y; range, 36-82 y) with 23 symptomatic stenoses
      of mesenteric arteries were treated with stent placement by a monorail technique
      in a radiologic intervention center over a period of 4.5 years. Clinical
      examinations and duplex sonography were used to evaluate the stents' patency and
      clinical success. Kaplan-Meier graphs were calculated to analyze the patency and
      freedom-from-symptom rate. RESULTS: Initial technical success rate was 22/23
      (96%). Mean follow-up was 17 months (range, 1-58 mo). Primary patency and primary
      clinical success rates were 82% and 78%, respectively. According to Kaplan-Meier
      tables, the patency rates were 96%, 87%, 76%, and 61% at 0, 1, 15, and 24 months,
      respectively, and the freedom-from-symptom rates were 95%, 90%, 72%, and 54% at
      0, 1, 24, and 30 months, respectively. No peri-interventional complications
      occurred. Two patients died of cardiac failure in the hospital within 30 days
      after intervention; deaths were not related to the intervention. CONCLUSIONS:
      Stent placement by a monorail technique in mesenteric arteries is an effective
      and safe treatment for symptomatic stenoses in patients with chronic mesenteric
      ischemia after a mean follow-up of 17 months.

PMID- 16614147
TI  - Stent implantation for acute iliac artery occlusions: initial experience.
AB  - PURPOSE: Treatment options for acute occlusion of the iliac arteries include
      surgical thrombectomy, surgical bypass, and endovascular interventions such as
      thrombolysis and mechanical thrombectomy with or without adjunctive angioplasty
      or stent implantation. Acute lesions are not usually treated by stent
      implantation for fear of distal embolism. The purpose of this study was to
      retrospectively review a single-center experience of primary iliac stent
      implantation for acute ischemia secondary to acute thrombosis. MATERIALS AND
      METHODS: Between April 2004 and August 2005, seven patients (five men and two
      women; mean age, 69.9 y; range, 53-93 y) underwent iliac stent implantation for
      the acute onset (within 12 days before presentation) of ipsilateral ischemic
      symptoms. Diagnostic angiography revealed occlusion of the common and external
      iliac arteries (n = 3) or external iliac artery (n = 4). Patients with rest pain
      (n = 6) were treated with unfractionated heparin. RESULTS: All acute occlusions
      were traversed by the guide wire with relative ease. Recanalization with stent
      implantation was successful in all cases without distal embolization. Five
      patients showed noticeable clinical improvement. Two elderly patients with
      isolated patent profunda segments with no demonstrable distal runoff vessels did
      not have long-term clinical improvement despite successful iliac recanalization.
      CONCLUSIONS: This small case series suggests that primary stent implantation for
      acute iliac occlusions with a patent common femoral artery under intravenous
      heparin protection may be a reasonable endovascular alternative to thrombolysis
      for patients who cannot tolerate the time delay to achieve thrombolysis or who
      have contraindications to thrombolysis. The safety of this technique may be
      comparable to that of primary stent implantation for chronic occlusions, but
      larger series would be necessary to confirm this.

PMID- 16614148
TI  - Withdrawal of port-catheter system for hepatic arterial infusion chemotherapy
      implanted with fixed catheter tip method.
AB  - PURPOSE: To evaluate the feasibility and safety of a method to withdraw port
      catheter systems implanted by the fixed catheter tip method. MATERIALS AND
      METHODS: Retrospective review was conducted of 14 cases of unresectable advanced
      liver cancer in which it was necessary to attempt 15 withdrawals of
      percutaneously placed implantable port-catheter systems. Reasons for withdrawal,
      withdrawal success, complications, and subsequent treatment of patient were
      evaluated. RESULTS: In 14 of the 15 procedures (93.3%), the port-catheter system
      was successfully retrieved. Because continuation of hepatic arterial infusion
      chemotherapy was necessary in 10 procedures, a second implantation was performed
      after withdrawal of the initial catheter. Only one complication occurred, in
      which the indwelling catheter was broken in the aorta during withdrawal.
      CONCLUSION: When retrieval of a port-catheter system implanted with the fixed
      catheter tip method is necessary, withdrawal can be accomplished safely with high
      frequency.

PMID- 16614149
TI  - Treatment of tracheobronchial obstruction with a polytetrafluoroethylene-covered
      retrievable expandable nitinol stent.
AB  - PURPOSE: To evaluate the clinical effectiveness of polytetrafluoroethylene (PTFE)
      covered retrievable expandable nitinol stents in tracheobronchial strictures.
      MATERIALS AND METHODS: With fluoroscopic guidance, PTFE-covered retrievable
      expandable nitinol stents were placed in 15 symptomatic patients with benign (n =
      6) or malignant (n = 9) tracheobronchial strictures. Complications and
      improvement in respiratory status were evaluated. Stents were removed electively
      6 months after placement in benign strictures or if complications occurred.
      Membrane degradation or separation from the wire mesh was evaluated in removed
      stents. RESULTS: A total of 17 stents were successfully placed and were well
      tolerated in all patients. Sputum retention, stent migration, and tissue
      hyperplasia occurred in 23.5% (n = 4), 17.6% (n = 3), and 17.6% (n = 3) of
      stents, respectively. A total of 11 stents were successfully removed electively 6
      months after placement (n = 4) or when complications occurred (n = 7). All 11
      such stents were removed without difficulty with use of standard techniques,
      antecedent balloon dilation being necessary in two cases as a result of tissue
      hyperplasia. No removed stent showed signs of membrane degradation, and two
      removed stents showed signs of membrane separation from the mesh. CONCLUSIONS:
      PTFE-covered retrievable expandable nitinol stents were effective in the
      treatment of tracheobronchial strictures. Stent removal was easy with use of
      standard techniques, and no removed stent showed evidence of membrane
      degradation.

PMID- 16614150
TI  - Comparison of adjunctive use of rofecoxib versus ibuprofen in the management of
      postoperative pain after uterine artery embolization.
AB  - PURPOSE: The primary purpose of the present study was to compare the
      antiinflammatory effectiveness of rofecoxib with that of ibuprofen in the first 5
      days after uterine artery embolization (UAE). The secondary aim was to compare
      pain levels and narcotic use among patients treated with different embolic
      agents. MATERIALS AND METHODS: From July 2003 to June 2004, 68 UAE procedures
      were performed by one of the authors (D.M.H.). Of this group, 50 women agreed to
      participate in this study. Exclusion criteria were limited to contraindication to
      either drug or current steroid or nonsteroidal antiinflammatory drug use. In a
      randomized, double-blinded fashion, patients received a numbered pill box that
      contained one of the two agents and its placebo counterpart. Four times per day
      for 5 days, patients recorded their level of pain on a visual analog scale and
      the amount of narcotic analgesic drug needed at that time. Score sheets were
      returned by mail after completion. During the course of the study, three embolic
      agents (Gold Embospheres, Contour SE particles, and Embospheres) were used in
      succession, with similar numbers of patients in each group. RESULTS: Four
      patients were excluded from analysis: two who were readmitted to the hospital for
      treatment of pain (one treated with each antiinflammatory medication) and two who
      failed to complete their score sheets. Subject demographics were very similar
      with respect to antiinflammatory drug treatment and embolic agent, except that
      the average age of patients in the Embosphere group was 6 years older than in the
      Embosphere Gold and Contour SE groups (P= .02). There was no difference in the
      pain level and narcotic drug intake between the two drug arms, but among embolic
      agents, the Embosphere Gold group tended to have a higher overall average pain
      score (P = .12), and the two patients readmitted were in this group. Patients in
      the Contour SE group tended to use a lower amount of narcotic drug than those in
      the other two embolic agent groups (P = .09). CONCLUSIONS: There was no
      difference between rofecoxib and ibuprofen with respect to postprocedural pain or
      narcotic use after UAE. Embolic agent appeared to have a greater impact, with
      patients in the Embosphere Gold group reporting higher pain scores and those in
      the Contour SE group requiring a lower amount of narcotic drug than those in the
      Embosphere Gold or Embosphere groups.

PMID- 16614151
TI  - Treatment strategy to optimize radiofrequency ablation for liver malignancies.
AB  - PURPOSE: The purposes of this study were to investigate a treatment strategy to
      increase liver tumor necrosis and minimize complications with ultrasound-guided
      percutaneous radiofrequency (RF) ablation and to evaluate its therapeutic
      efficacy. MATERIALS AND METHODS: A total of 332 patients with 503 liver
      malignancies underwent RF ablation according to a mathematical protocol with
      adjunctive measures. In the 332 patients, 205 had 308 hepatocellular carcinomas
      (HCCs) with a mean largest diameter of 4.1 cm and 127 had 195 metastatic liver
      carcinomas (MLCs) with a mean largest diameter of 3.9 cm. In patients with HCC,
      60 (29.3%) had stage I/II disease and 145 (70.7%) had stage III/IV disease.
      Depending on tumor size, shape, and location, a defined treatment strategy was
      adopted that consisted of a mathematical protocol, an individualized protocol,
      and adjunctive measures. The mathematical protocol was followed for tumors larger
      than 3.5 cm. The individualized protocol was used for tumors located adjacent to
      the diaphragm, gastrointestinal tract, or gallbladder. Some adjunctive measures
      such as supplementary fine needle localization, local saline solution injection,
      and feeding vessel ablation were used to deal with different features of these
      liver tumors. Patients were followed regularly to assess treatment efficiency,
      and the tumor was considered to have early complete necrosis if no viability was
      found on enhanced computed tomography 1 month after RF ablation. RESULTS: In this
      series, the early necrosis rates were 95.8% for HCC (295 of 308 tumors), 94.9%
      for MLC (185 of 195 tumors), 91.3% for tumors larger than 3.5 cm (189 of 207
      tumors), 90.7% for tumors near the gastrointestinal tract (49 of 54 tumors),
      91.5% for tumors near the diaphragm (86 of 94 tumors), and 90.6% for tumors near
      the gallbladder (48 of 53 tumors). The local recurrence rates were 10.7% for HCC
      (33 of 308 tumors) and 14.9% for MLC (29 of 195 tumors). The 1-, 2-, and 3-year
      overall survival rates were 89.6%, 69.4%, and 59.6%, respectively, for HCC and
      80.3%, 52.8%, and 30.9%, respectively, for MLC. The 1-, 2-, and 3-year survival
      rates in 60 patients with stage I/II HCC were 93.7%, 87.1%, and 76.2%,
      respectively. The incidence of major complications was 1.4% (eight of 574
      sessions), which included of three hemorrhages, four injuries to adjacent
      structures, and one case of needle tract seeding. CONCLUSION: In RF ablation of
      hepatic tumors, application of a proper protocol and adjunctive measures play
      important roles in improving tumor necrosis rate and minimizing potential
      complications.

PMID- 16614152
TI  - Optional inferior vena cava filter retrieval with retained thrombus: an in vitro
      model.
AB  - PURPOSE: Retrieval of an optional inferior vena cava (IVC) filter with retained
      thrombus may result in pulmonary emboli if the trapped thrombus is not removed
      along with the filter. An in vitro model was developed to determine the fate of
      trapped thrombus during filter removal. MATERIALS AND METHODS: An in vitro IVC
      flow model was created with 25-mm inner diameter tubing and a 50% glycerol/water
      solution. Three different optional filters-Recovery (Bard, Tempe, AZ), Gunther
      Tulip (Cook Inc., Bloomington IN), and OptEase (Cordis Endovascular/Johnson &
      Johnson, Warren, NJ)-were evaluated in the study. A known mass of mature thrombus
      (porcine, aged 1 wk) was trapped within the optional filters. The filters were
      then retrieved according to the manufacturers' protocol, and the mass of thrombus
      recovered with the filter was determined. For each filter, five iterations were
      performed with initial thrombus sizes less than 1 g (group A) and an additional
      five iterations with initial thrombus sizes greater than 1 g (group B). RESULTS:
      Thrombi from group A were statistically significantly smaller than those from
      group B (P < .0001). Retrieval of the Recovery filter resulted in an average of
      25% (range, 0%-53%) and 4% (range, 0%-7%) of the clot being removed in group A
      and group B, respectively. Retrieval of the Gunther-Tulip filter resulted in an
      average of 22% (group A) and 13% (group B) of the clot being removed. Retrieval
      of the OptEase filter resulted in an average of 43% (group A) and 0% (group B) of
      the clot being removed. CONCLUSIONS: In our in vitro model, we have established
      that the mass of thrombus retrieved with optional filters is only a fraction of
      the initial clot burden. Because of the risk of pulmonary emboli, care should be
      taken when IVC filters with large amounts of trapped thrombus are removed from
      patients.

PMID- 16614153
TI  - Comparison of the Texan foreign body retrieval device and the Amplatz goose neck
      snare in vivo and in vitro.
AB  - PURPOSE: To compare the capturing ability of the Texan foreign body retrieval
      device with that of the Amplatz gooseneck snare in a swine model and to analyze
      their capturing mechanisms. MATERIALS AND METHODS: The Texan device with a < or =
      30-mm adjustable loop was compared with the 5-mm, 15-mm, and 35-mm Amplatz snares
      for retrieval of foreign bodies from the iliac vein, infrarenal aorta, inferior
      vena cava, and stomach. Capture times by two investigators were compared.
      RESULTS: All 24 attempts with the Texan device were successful, as were 21 of 23
      attempts with the Amplatz snare; two attempts with the 5-mm Amplatz snare were
      abandoned, and the failures were attributed to the suboptimal size of the snare.
      Other than the two abandoned attempts, there was no difference between the
      capturing performances of the Texan device and the 5-mm, 15-mm, and 35-mm Amplatz
      snares when they were compared side by side. In all vascular interventions,
      however, the Texan device performed significantly better in capture times than
      did the 5-mm and 15-mm Amplatz snare (P = .015). In all interventions, the Texan
      device performed significantly better in capture times than did all three sizes
      of the Amplatz snare (P= .012). CONCLUSION: The overall performance of the Texan
      device based on its capturing ability was significantly better than that of the
      Amplatz snares. The adjustability of the loop and the more versatile capturing
      technique made capture and retrieval of foreign bodies easier.

PMID- 16614154
TI  - Hepatocellular carcinoma: transcatheter arterial chemoembolization of the gonadal
      artery.
AB  - Over the past 9 years, the authors have identified gonadal arteries supplying
      hepatocellular carcinoma in seven of 4,438 patients (0.16%) whom they attempted
      to treat by transcatheter arterial chemoembolization. All seven patients had
      tumors in the Couinaud segment 6 (S6) of the liver (mean size, 6.8 cm). The
      gonadal arteries in all seven patients showed anatomic variations, including a
      high origin (n = 3) and a common trunk with the adrenal artery (n = 4). The
      gonadal artery with anatomic variation may supply hepatocellular carcinomas
      located in liver S6.

PMID- 16614155
TI  - Transjugular intrahepatic portosystemic shunt creation in a polycystic liver
      facilitated by hybrid cross-sectional/angiographic imaging.
AB  - Polycystic liver disease (PCLD) has long been considered to represent a
      contraindication to transjugular intrahepatic portosystemic shunt (TIPS)
      creation, primarily because of the risk of hemorrhage. Three-dimensional (3D)
      navigation within the enlarged and potentially disorienting parenchyma can now be
      performed during the procedure with the development of C-arm cone-beam computed
      tomography, which relies on the same equipment already used for angiography. Such
      a hybrid 3D reconstruction-enabled angiography system was used for safe image
      guidance of a TIPS procedure in a patient with PCLD. This technology has the
      potential to expedite any image-guided procedure that requires 3D navigation.

PMID- 16614156
TI  - Successful interventional treatment of a spontaneous right common iliac artery
      dissection extending retrogradely into the left external iliac artery.
AB  - Spontaneous dissection of the iliac artery is very rare. In the present report, a
      patient presented with progressive right lower extremity pain and claudication
      and received a diagnosis of the even rarer condition of a spontaneous right
      common iliac artery dissection extending retrogradely into the contralateral left
      external iliac artery through the lower abdominal aorta. Treatment with primary
      stent-graft and stent placement followed by balloon angioplasty was successful.

PMID- 16614157
TI  - Carbon dioxide-enhanced sonographically guided radiofrequency ablation plus
      transcatheter arterial chemoembolization for hepatocellular carcinoma.
AB  - A 78-year-old man had a history of blood transfusion and hepatitis C virus
      related liver cirrhosis. He was admitted to the authors' hospital with a
      hepatocellular carcinoma just below the right hemidiaphragm. Although the lesion
      was not well visualized with standard sonography, it was clearly defined by
      performance of sonography with intraarterial injection of carbon dioxide,
      allowing safe and accurate radiofrequency ablation. To increase the extent of
      tumor ablation, transcatheter arterial chemoembolization was performed
      immediately before radiofrequency ablation. By concomitant application of these
      two techniques, complete tumor necrosis was achieved without the need to perform
      additional ablation.

PMID- 16614158
TI  - Complete necrosis of a spinal giant cell tumor after vertebroplasty.
AB  - In this case report, histologic evidence of complete tumor necrosis subsequent to
      injection of polymethylmethacrylate in a vertebral giant cell tumor is described.
      Radiologic and histologic findings are discussed, and literature pertaining to
      vertebroplasty-induced cell damaged is reviewed.

PMID- 16614159
TI  - Ureterocutaneous fistula and urostomy exclusion with use of a covered wallstent.
AB  - The present report describes a case of urostomy breakdown and failed urinary
      diversion with bilateral nephrostomy drainage treated with transrenal placement
      of a covered stent. Covered stents can be used successfully for the exclusion of
      ureterocutaneous fistulas and urostomies with the potential for ureteric
      occlusion.

PMID- 16614160
TI  - Progressive asymptomatic occlusion of a TIPS in a patient with Budd-Chiari
      syndrome.

PMID- 16614161
TI  - The "endoyear": a new unit of time.

PMID- 16614162
TI  - Percutaneous retrieval of a vena tech LP filter after failure of filter opening.

PMID- 16614164
TI  - Isolation and identification of nine sulfated glycosphingolipids containing two
      unique sulfated gangliosides from the African green monkey kidney cells, Verots
      S3, and their possible metabolic pathways.
AB  - Verots S3 cells derived from the African green monkey kidney were revealed to
      contain nine types of sulfoglycolipids by incorporating [35S]sulfate. These
      sulfated glycolipids were separated by DEAE-Sephadex column chromatography and
      preparative thin-layer chromatography (TLC). The major sulfoglycolipids were
      characterized using TLC, gas-liquid chromatography (GLC), mass spectrometry,
      solvolysis, TLC immunostaining, and nuclear magnetic resonance spectra as
      follows: V1, SM4s (GalCer I3-sulfate); V2, SM3 (LacCer II3-sulfate); V3, SM2a
      (Gg3Cer II3-sulfate); V4, globopentaosyl ceramide sulfate (Gb5Cer V3-sulfate);
      V5, (Gg4Cer II3-sulfate, IV3-NeuAc); V6, SB1a (Gg4Cer II3, IV3-bis-sulfate); and
      V8, (Gg4Cer II3-NeuAc, IV3-sulfate). Both V5 and V8 were sulfated gangliosides
      comprising both N-acetyl neuraminic acid and sulfate, and this was the first
      report on V8. A minor component V7 was identified as SM1a (Gg4Cer II3-sulfate)
      based on its behavior in TLC, GLC, and liquid secondary ion mass spectroscopy. It
      was postulated that this substance was a precursor of V6 (SB1a) and V5 (Gg4Cer
      II3-sulfate, IV3-NeuAc), and to date, its presence has not been demonstrated in
      nature. Another minor component V9 was identified as glucosyl ceramide sulfate
      based on its migration in TLC and GLC. This renal cell line was shown to be an
      excellent model for studying the metabolism and function of sulfoglycolipids.

PMID- 16614165
TI  - Human SII and posterior insula differently encode thermal laser stimuli.
AB  - The SII area and the posterior insular region are both activated by thermal
      stimuli in functional imaging studies. However, controversy remains as to a
      possible differential encoding of thermal intensity by each of these 2 contiguous
      areas. Using CO(2) laser stimulations, we analyzed the modifications induced by
      increasing thermal energy on evoked potentials recorded with electrodes implanted
      within SII and posterior insula in patients referred for presurgical evaluation
      of epilepsy. Although increasing stimulus intensities enhanced both SII and
      insular responses, the "dynamics" of their respective amplitude changes were
      different. SII responses were able to encode gradually the intensity of stimuli
      from sensory threshold up to a level next to pain threshold but tended to show a
      ceiling effect for higher painful intensities. In contrast, the posterior insular
      cortex failed to detect nonnoxious laser pulses but reliably encoded stimulus
      intensity variations at painful levels, without showing saturation effects for
      intensities above pain threshold. According to these results, one can assume that
      insular cortex could be more involved in the triggering of affective recognition
      of, and motor reaction to, noxious stimuli, whereas SII would be more dedicated
      to finer-grain discrimination of stimulus intensity, from nonpainful to painful
      levels.

PMID- 16614166
TI  - Paclitaxel and docetaxel stimulation of doxorubicinol formation in the human
      heart: implications for cardiotoxicity of doxorubicin-taxane chemotherapies.
AB  - Antitumor therapy with the anthracycline doxorubicin is limited by a dose-related
      cardiotoxicity that is aggravated by a concomitant administration of the taxane
      paclitaxel. Previous limited studies with isolated human heart cytosol showed
      that paclitaxel was able to stimulate an NADPH-dependent reduction of doxorubicin
      to its toxic secondary alcohol metabolite doxorubicinol. Here we characterized
      that 0.25 to 2.5 microM paclitaxel caused allosteric effects that increased
      doxorubicinol formation in human heart cytosol, whereas 5 to 10 microM paclitaxel
      decreased doxorubicinol formation. The closely related taxane docetaxel caused
      similar effects. Basal or taxane-stimulated doxorubicinol formation was blunted
      by 2,7-difluorospirofluorene-9,5'-imidazolidine-2',4'-dione (AL1576), a specific
      inhibitor of aldehyde reductases. Doxorubicinol was measured also in the cytosol
      of human myocardial strips incubated in plasma and exposed to doxorubicin in the
      absence or presence of paclitaxel or docetaxel and their clinical vehicles
      Cremophor EL or polysorbate 80. Low concentrations of taxanes stimulated
      doxorubicinol formation, whereas high concentrations decreased it. Doxorubicinol
      formation reached its maximum on adding plasma with 6 microM paclitaxel or
      docetaxel; this corresponded to the partitioning of 1.5 to 2.5 microM taxanes in
      the cytosol of the strips. Taxane-stimulated doxorubicinol formation was not
      mediated by vehicles, nor was it caused by increased doxorubicin uptake or de
      novo protein synthesis; however, doxorubicinol formation was blunted by AL1576.
      These results show that allosteric interactions with cytoplasmic aldehyde
      reductases enable paclitaxel or docetaxel to stimulate doxorubicinol formation in
      human heart. This information serves metabolic insights into the risk of
      cardiotoxicity induced by doxorubicin-taxane therapies.

PMID- 16614167
TI  - p53 suppression of arsenite-induced mitotic catastrophe is mediated by
      p21CIP1/WAF1.
AB  - Arsenic trioxide, an acute promyelocytic leukemia chemotherapeutic, may be an
      efficacious treatment for other cancers. Understanding the mechanism as well as
      genetic and molecular characteristics associated with sensitivity to arsenite
      induced cell death is key to providing effective chemotherapeutic usage of
      arsenite. Arsenite sensitivity correlates with deficient p53 pathways in multiple
      cell lines. The role of p53 in preventing arsenite-induced mitotic arrest
      associated apoptosis (MAAA), a form of mitotic catastrophe, was examined in TR9-7
      cells, a model cell line with p53 exogenously regulated in a tetracycline-off
      expression system. Arsenite activated G1 and G2 cell cycle checkpoints
      independently of p53, but mitotic catastrophe occurred preferentially in p53-
      cells. Cyclin B/CDC2(CDK1) stabilization and caspase-3 activation persisted in
      arsenite-treated p53- cells consistent with MAAA/mitotic catastrophe. N
      Benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone, a pan-caspase inhibitor,
      completely abolished arsenite-induced MAAA/mitotic catastrophe and greatly
      increased the mitotic index. WEE1 and p21CIP1/WAF1 inhibit cyclin B/CDC2 by CDC2
      tyrosine-15 phosphorylation and direct binding, respectively. CDC2-Y15-P was
      transiently elevated in arsenite-treated p53+ cells but persisted in p53- cells.
      Arsenite induced p53-S15-P and p21CIP1/WAF1 only in p53+ cells. P21CIP1/WAF1
      siRNA-treated p53+ cells were similar to p53- cells in mitotic index and cell
      cycle protein levels. p53-inducible proteins GADD45alpha and 14-3-3sigma are
      capable of inhibiting cyclin B/CDC2 but did not play a p53-dependent role in
      mitotic escape in TR9-7 cells. The data indicate that p53 mediates cyclin B/CDC2
      inactivation and mitotic release directly via p21CIP1/WAF1 induction.

PMID- 16614168
TI  - Differentiation of arrhythmia risk of the antibacterials moxifloxacin,
      erythromycin, and telithromycin based on analysis of monophasic action potential
      duration alternans and cardiac instability.
AB  - Antibacterial drugs are known to have varying degrees of cardiovascular liability
      associated with QT prolongation that can lead to the ventricular arrhythmia
      torsade de pointes. The purpose of these studies was to compare the assessment
      for the arrhythmogenic risk of moxifloxacin, erythromycin, and telithromycin.
      Each drug caused dose-dependent inhibition of the rapidly activating delayed
      rectifier potassium current encoded by the human ether-a-go-go-related gene
      (hERG) with IC20 concentrations of 31 microM (moxifloxacin), 21 microM
      (erythromycin), and 11 microM (telithromycin). These drugs were also evaluated in
      an anesthetized guinea pig model to measure changes in monophasic action
      potential duration (MAPD) and to quantify beat-to-beat alternations in MAPD
      during rapid ventricular pacing. Moxifloxacin dose dependently increased MAPD and
      caused a rate-dependent increase in alternans at the highest achieved free drug
      concentration (41 microM). Erythromycin also increased MAPD at its highest free
      drug concentration (58 microM), but alternans occurred at a relatively lower
      therapeutic multiple (13.9 microM), and the magnitude of alternans at higher
      concentrations was independent of pacing rate. Further analysis of the data
      showed that the beat-to-beat pattern of alternans with erythromycin was less
      stable than that with moxifloxacin and suggestive of greater arrhythmogenic
      liability. In contrast to erythromycin and moxifloxacin, telithromycin decreased
      both MAPD and alternans at the highest achievable drug concentration (7.9
      microM). The relative risk at therapeutic concentrations is
      erythromycin>moxifloxacin>telithromycin and appears to be consistent with
      clinical observations of torsade de pointes in patients.

PMID- 16614169
TI  - Selective inhibition of eosinophil influx into the lung by small molecule CC
      chemokine receptor 3 antagonists in mouse models of allergic inflammation.
AB  - CC chemokine receptor (CCR) 3 is a chemokine receptor implicated in recruiting
      cells, particularly eosinophils (EPhi), to the lung in episodes of allergic
      asthma. To investigate the efficacy of selective, small molecule antagonists of
      CCR3, we developed a murine model of EPhi recruitment to the lung. Murine eotaxin
      was delivered intranasally to mice that had previously received i.p. injections
      of ovalbumin (OVA), and the effects were monitored by bronchoalveolar lavage. A
      selective eosinophilic influx was produced in animals receiving eotaxin but not
      saline. Furthermore, the number of EPhi was concentration- and time-dependent.
      Although anti-CCR3 antibody reduced the number of EPhi, the effect of eotaxin in
      OVA-sensitized mice was not a direct chemotactic stimulus because mast cell
      deficiency (in WBB6F1-Kitw/Kitw-v mice) significantly reduced the response. Two
      representative small molecule CCR3 antagonists from our program were
      characterized as being active at mouse CCR3. They were administered p.o. to wild
      type mice and found to reduce eotaxin-elicited EPhi selectively in a dose
      dependent manner. Pump infusion of one of the inhibitors to achieve steady-state
      levels showed that efficacy was not achieved at plasma concentrations equivalent
      to the in vitro chemotaxis IC90 but only at much higher concentrations. To extend
      the results from our recruitment model, we tested one of the inhibitors in an
      allergenic model of airway inflammation, generated by adoptive transfer of OVA
      sensitive murine T helper 2 cells and aerosolized OVA challenge of recipient
      mice, and found that it inhibited EPhi recruitment. We conclude that small
      molecule CCR3 antagonists reduce pulmonary eosinophilic inflammation elicited by
      chemokine or allergenic challenge.

PMID- 16614170
TI  - Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle
      release.
AB  - The molecular organization of presynaptic active zones during calcium influx
      triggered neurotransmitter release is the focus of intense investigation. The
      Drosophila coiled-coil domain protein Bruchpilot (BRP) was observed in donut
      shaped structures centered at active zones of neuromuscular synapses by using
      subdiffraction resolution STED (stimulated emission depletion) fluorescence
      microscopy. At brp mutant active zones, electron-dense projections (T-bars) were
      entirely lost, Ca2+ channels were reduced in density, evoked vesicle release was
      depressed, and short-term plasticity was altered. BRP-like proteins seem to
      establish proximity between Ca2+ channels and vesicles to allow efficient
      transmitter release and patterned synaptic plasticity.

PMID- 16614171
TI  - Cyclopropenylidenes: from interstellar space to an isolated derivative in the
      laboratory.
AB  - Like many of the molecular species that have been detected in the interstellar
      medium, the singlet carbene cyclopropenylidene (C3H2) has been presumed to be too
      unstable to isolate in the laboratory. However, by appending pi-electron-donating
      amino groups to the triangular skeleton, we prepared a cyclopropenylidene
      derivative that is stable at room temperature. In contrast to previously isolated
      carbenes, this compound does not require a heteroatom adjacent to the electron
      deficient carbon to confer stability. Despite the presence of amino groups, the
      geometric parameters of the cyclic skeleton, revealed by x-ray crystallography,
      are only slightly perturbed relative to those of the calculated structure of
      unsubstituted cyclopropenylidene. Stable cyclopropenylidene derivatives might
      thus serve as models for a better understanding of the formation of carbon
      bearing molecules in the interstellar medium.

PMID- 16614173
TI  - Electronic confinement and coherence in patterned epitaxial graphene.
AB  - Ultrathin epitaxial graphite was grown on single-crystal silicon carbide by
      vacuum graphitization. The material can be patterned using standard
      nanolithography methods. The transport properties, which are closely related to
      those of carbon nanotubes, are dominated by the single epitaxial graphene layer
      at the silicon carbide interface and reveal the Dirac nature of the charge
      carriers. Patterned structures show quantum confinement of electrons and phase
      coherence lengths beyond 1 micrometer at 4 kelvin, with mobilities exceeding 2.5
      square meters per volt-second. All-graphene electronically coherent devices and
      device architectures are envisaged.

PMID- 16614172
TI  - An SNP caused loss of seed shattering during rice domestication.
AB  - Loss of seed shattering was a key event in the domestication of major cereals. We
      revealed that the qSH1 gene, a major quantitative trait locus of seed shattering
      in rice, encodes a BEL1-type homeobox gene and demonstrated that a single
      nucleotide polymorphism (SNP) in the 5' regulatory region of the qSH1 gene caused
      loss of seed shattering owing to the absence of abscission layer formation.
      Haplotype analysis and association analysis in various rice collections revealed
      that the SNP was highly associated with shattering among japonica subspecies of
      rice, implying that it was a target of artificial selection during rice
      domestication.

PMID- 16614174
TI  - Nick Cozzarelli.

PMID- 16614175
TI  - International exchanges. Secret Pyongyang meeting builds science ties between two
      Koreas.

PMID- 16614176
TI  - Clinical medicine. Accident prompts a closer look at antibody trials.

PMID- 16614177
TI  - Archaeology. Iraq antiquities find sparks controversy.

PMID- 16614178
TI  - Chemistry. Catalyst combo offers new route for turning waste products into fuel.

PMID- 16614179
TI  - Nuclear power. DOE asked to fill in the blanks on fuel recycling research plan.

PMID- 16614180
TI  - Peer review. Australia's proposed U.K.-style merit ranking stirs debate.

PMID- 16614181
TI  - U.S. immigration. Congress weighs steps to retain foreign talent.

PMID- 16614182
TI  - Development. Two unexpected players add twists to liver's comeback story.

PMID- 16614183
TI  - Paleoanthropology. Fossils clinch identity of Lucy's ancestor.

PMID- 16614184
TI  - Astrobiology science conference 2006. Life slow enough to live on radioactivity.

PMID- 16614185
TI  - Astrobiology science conference 2006. Diversity before life.

PMID- 16614186
TI  - Nuclear radiation. Return to the inferno: Chornobyl after 20 years.

PMID- 16614187
TI  - Ecology. Once a terminal case, the north Aral Sea shows new signs of life.

PMID- 16614188
TI  - Immunology. Targeting the tolls.

PMID- 16614189
TI  - Computer science. Life in silico: a different kind of intelligent design.

PMID- 16614190
TI  - Nuclear physics. Scheme for boiling nuclear matter gathers steam at accelerator
      lab.

PMID- 16614196
TI  - Retraction.

PMID- 16614197
TI  - Marketing drugs too early in testing.

PMID- 16614198
TI  - Life-span extension in yeast.

PMID- 16614199
TI  - Archaeopteryx: the lost evidence.

PMID- 16614200
TI  - Comment on "The illusion of invariant quantities in life histories".
AB  - Nee et al. (Reports, 19 August 2005, p. 1236) used a null model to argue that
      life history invariants are illusions. We show that their results are largely
      inconsequential for life history theory because the authors confound two
      definitions of invariance, and rigorous analysis of their null model demonstrates
      that it does not match observed data.

PMID- 16614201
TI  - Science communication. Environmental science adrift in the blogosphere.

PMID- 16614202
TI  - Earthquake anniversary. Halfway through Reid's cycle and counting.

PMID- 16614203
TI  - Earthquake anniversary. Can buildings be made earthquake-safe?

PMID- 16614204
TI  - Immunology. Thoracic thymus, exclusive no longer.

PMID- 16614205
TI  - Molecular biology. Managing associations between different chromosomes.

PMID- 16614206
TI  - Biochemistry. Enzyme motions inside and out.

PMID- 16614208
TI  - Mass spectrometry and protein analysis.
AB  - Mass spectrometry is a central analytical technique for protein research and for
      the study of biomolecules in general. Driven by the need to identify,
      characterize, and quantify proteins at ever increasing sensitivity and in ever
      more complex samples, a wide range of new mass spectrometry-based analytical
      platforms and experimental strategies have emerged. Here we review recent
      advances in mass spectrometry instrumentation in the context of current and
      emerging research strategies in protein science.

PMID- 16614209
TI  - The fluorescent toolbox for assessing protein location and function.
AB  - Advances in molecular biology, organic chemistry, and materials science have
      recently created several new classes of fluorescent probes for imaging in cell
      biology. Here we review the characteristic benefits and limitations of
      fluorescent probes to study proteins. The focus is on protein detection in live
      versus fixed cells: determination of protein expression, localization, activity
      state, and the possibility for combination of fluorescent light microscopy with
      electron microscopy. Small organic fluorescent dyes, nanocrystals ("quantum
      dots"), autofluorescent proteins, small genetic encoded tags that can be
      complexed with fluorochromes, and combinations of these probes are highlighted.

PMID- 16614210
TI  - New tools provide new insights in NMR studies of protein dynamics.
AB  - There is growing evidence that structural flexibility plays a central role in the
      function of protein molecules. Many of the experimental data come from nuclear
      magnetic resonance (NMR) spectroscopy, a technique that allows internal motions
      to be probed with exquisite time and spatial resolution. Recent methodological
      advancements in NMR have extended our ability to characterize protein dynamics
      and promise to shed new light on the mechanisms by which these molecules
      function. Here, we present a brief overview of some of the new methods, together
      with applications that illustrate the level of detail at which protein motions
      can now be observed.

PMID- 16614211
TI  - Living cells as test tubes.
AB  - The combination of specific probes and advanced optical microscopy now allows
      quantitative probing of biochemical reactions in living cells. On selected
      systems, one can detect and track a particular protein with single-molecule
      sensitivity, nanometer spatial precision, and millisecond time resolution.
      Metabolites, usually difficult to detect, can be imaged and monitored in living
      cells with coherent anti-Stokes Raman scattering microscopy. Here, we describe
      the application of these techniques in studying gene expression, active
      transport, and lipid metabolism.

PMID- 16614212
TI  - Thermal preference and tolerance of alvinellids.
AB  - The highest oceanic temperatures are found at hydrothermal vents, where the
      polychaete Paralvinella sulfincola lives on vent sulfides within steep and
      dynamic thermal gradients. To determine P. sulfincola thermotolerance and
      preference, we developed a high-pressure aquarium that mimics in situ thermal
      gradients and permits P. sulfincola to move within the gradient. These
      polychaetes were thermotaxic, preferring temperatures of 40 degrees to 50 degrees
      C. Some individuals remained at 50 degrees C for 7 hours (the duration of the
      experiment), whereas others endured exposure to 55 degrees C for over 15 minutes,
      demonstrating that alvinellids prefer high temperatures and are among the most
      thermotolerant of marine organisms.

PMID- 16614213
TI  - Nuclear receptor-dependent bile acid signaling is required for normal liver
      regeneration.
AB  - Liver mass depends on one or more unidentified humoral signals that drive
      regeneration when liver functional capacity is diminished. Bile acids are
      important liver products, and their levels are tightly regulated. Here, we
      identify a role for nuclear receptor-dependent bile acid signaling in normal
      liver regeneration. Elevated bile acid levels accelerate regeneration, and
      decreased levels inhibit liver regrowth, as does the absence of the primary
      nuclear bile acid receptor FXR. We propose that FXR activation by increased bile
      acid flux is a signal of decreased functional capacity of the liver. FXR, and
      possibly other nuclear receptors, may promote homeostasis not only by regulating
      expression of appropriate metabolic target genes but also by driving homeotrophic
      liver growth.

PMID- 16614214
TI  - Atomic description of an enzyme reaction dominated by proton tunneling.
AB  - We present an atomic-level description of the reaction chemistry of an enzyme
      catalyzed reaction dominated by proton tunneling. By solving structures of
      reaction intermediates at near-atomic resolution, we have identified the reaction
      pathway for tryptamine oxidation by aromatic amine dehydrogenase. Combining
      experiment and computer simulation, we show proton transfer occurs predominantly
      to oxygen O2 of Asp(128)beta in a reaction dominated by tunneling over
      approximately 0.6 angstroms. The role of long-range coupled motions in promoting
      tunneling is controversial. We show that, in this enzyme system, tunneling is
      promoted by a short-range motion modulating proton-acceptor distance and no long
      range coupled motion is required.

PMID- 16614215
TI  - Piezoelectric nanogenerators based on zinc oxide nanowire arrays.
AB  - We have converted nanoscale mechanical energy into electrical energy by means of
      piezoelectric zinc oxide nanowire (NW) arrays. The aligned NWs are deflected with
      a conductive atomic force microscope tip in contact mode. The coupling of
      piezoelectric and semiconducting properties in zinc oxide creates a strain field
      and charge separation across the NW as a result of its bending. The rectifying
      characteristic of the Schottky barrier formed between the metal tip and the NW
      leads to electrical current generation. The efficiency of the NW-based
      piezoelectric power generator is estimated to be 17 to 30%. This approach has the
      potential of converting mechanical, vibrational, and/or hydraulic energy into
      electricity for powering nanodevices.

PMID- 16614216
TI  - Control of electron localization in molecular dissociation.
AB  - We demonstrated how the subcycle evolution of the electric field of light can be
      used to control the motion of bound electrons. Results are presented for the
      dissociative ionization of deuterium molecules (D2 --> D+ + D), where asymmetric
      ejection of the ionic fragment reveals that light-driven intramolecular
      electronic motion before dissociation localizes the electron on one of the two D+
      ions in a controlled way. The results extend subfemtosecond electron control to
      molecules and provide evidence of its usefulness in controlling reaction
      dynamics.

PMID- 16614217
TI  - Hardening by annealing and softening by deformation in nanostructured metals.
AB  - We observe that a nanostructured metal can be hardened by annealing and softened
      when subsequently deformed, which is in contrast to the typical behavior of a
      metal. Microstructural investigation points to an effect of the structural scale
      on fundamental mechanisms of dislocation-dislocation and dislocation-interface
      reactions, such that heat treatment reduces the generation and interaction of
      dislocations, leading to an increase in strength and a reduction in ductility. A
      subsequent deformation step may restore the dislocation structure and facilitate
      the yielding process when the metal is stressed. As a consequence, the strength
      decreases and the ductility increases. These observations suggest that for
      materials such as the nanostructured aluminum studied here, deformation should be
      used as an optimizing procedure instead of annealing.

PMID- 16614218
TI  - Diels-alder in aqueous molecular hosts: unusual regioselectivity and efficient
      catalysis.
AB  - Self-assembled, hollow molecular structures are appealing as synthetic hosts for
      mediating chemical reactions. However, product binding has inhibited catalytic
      turnover in such systems, and selectivity has rarely approached the levels
      observed in more structurally elaborate natural enzymes. We found that an aqueous
      organopalladium cage induces highly unusual regioselectivity in the Diels-Alder
      coupling of anthracene and phthalimide guests, promoting reaction at a terminal
      rather than central anthracene ring. Moreover, a similar bowl-shaped host attains
      efficient catalytic turnover in coupling the same substrates (although with the
      conventional regiochemistry), most likely because the product geometry inhibits
      the aromatic stacking interactions that attract the planar reagents to the host.

PMID- 16614219
TI  - Double perovskites as anode materials for solid-oxide fuel cells.
AB  - Extensive efforts to develop a solid-oxide fuel cell for transportation, the
      bottoming cycle of a power plant, and distributed generation of electric energy
      are motivated by a need for greater fuel efficiency and reduced air pollution.
      Barriers to the introduction of hydrogen as the fuel have stimulated interest in
      developing an anode material that can be used with natural gas under operating
      temperatures 650 degrees C < T < 1000 degrees C. Here we report identification of
      the double perovskites Sr2Mg(1-x)MnxMoO(6-delta) that meet the requirements for
      long-term stability with tolerance to sulfur and show a superior single-cell
      performance in hydrogen and methane.

PMID- 16614220
TI  - Catalytic alkane metathesis by tandem alkane dehydrogenation-olefin metathesis.
AB  - With petroleum supplies dwindling, there is increasing interest in selective
      methods for transforming other carbon feedstocks into hydrocarbons suitable for
      transportation fuel. We report the development of highly productive, well
      defined, tandem catalytic systems for the metathesis of n-alkanes. Each system
      comprises one molecular catalyst (a "pincer"-ligated iridium complex) that
      effects alkane dehydrogenation and olefin hydrogenation, plus a second catalyst
      (molecular or solid-phase) for olefin metathesis. The systems all show complete
      selectivity for linear (n-alkane) product. We report one example that achieves
      selectivity with respect to the distribution of product molecular weights, in
      which n-decane is the predominant high-molecular-weight product of the metathesis
      of two moles of n-hexane.

PMID- 16614221
TI  - High natural aerosol loading over boreal forests.
AB  - Aerosols play a key role in the radiation balance of the atmosphere. Here, we
      present evidence that the European boreal region is a substantial source of both
      aerosol mass and aerosol number. The investigation supplies a straightforward
      relation between emissions of monoterpenes and gas-to-particle formation over
      regions substantially lacking in anthropogenic aerosol sources. Our results show
      that the forest provides an aerosol population of 1000 to 2000 particles of
      climatically active sizes per cubic centimeter during the late spring to early
      fall period. This has important implications for radiation budget estimates and
      relevancy for the evaluation of feedback loops believed to determine our future
      climate.

PMID- 16614222
TI  - A bifurcating pathway directs abscisic acid effects on stomatal closure and
      opening in Arabidopsis.
AB  - Terrestrial plants lose water primarily through stomata, pores on the leaves. The
      hormone abscisic acid (ABA) decreases water loss by regulating opening and
      closing of stomata. Here, we show that phospholipase Dalpha1 (PLDalpha1) mediates
      the ABA effects on stomata through interaction with a protein phosphatase 2C
      (PP2C) and a heterotrimeric GTP-binding protein (G protein) in Arabidopsis.
      PLDalpha1-produced phosphatidic acid (PA) binds to the ABI1 PP2C to signal ABA
      promoted stomatal closure, whereas PLDalpha1 and PA interact with the Galpha
      subunit of heterotrimeric G protein to mediate ABA inhibition of stomatal
      opening. The results reveal a bifurcating signaling pathway that regulates plant
      water loss.

PMID- 16614223
TI  - Selection on gamete recognition proteins depends on sex, density, and genotype
      frequency.
AB  - Gamete recognition proteins can evolve at astonishing rates and lie at the heart
      of reproductive isolation and speciation in diverse taxa. However, the source of
      selection driving this evolution remains unknown. We report on how the sperm
      bindin genotype influences reproductive success under natural conditions. An
      interaction between genotype frequency and spawning density determines how sperm
      bindin genotype influences reproductive success. Common genotypes are selected
      under sperm-limited conditions, whereas rare genotypes are selected under
      conditions of intense sperm competition and sexual conflict. Variation in the
      evolutionary rates of bindin may reflect historic differences in sperm
      availability.

PMID- 16614224
TI  - CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1.
AB  - Gene transcription may be regulated by remote enhancer or insulator regions
      through chromosome looping. Using a modification of chromosome conformation
      capture (3C) and fluorescence in situ hybridization, we found that one allele of
      the insulin-like growth factor 2 (Igf2)/H19 imprinting control region (ICR) on
      chromosome 7 colocalized with one allele of Wsb1/Nf1 on chromosome 11. Omission
      of CCCTC-binding factor (CTCF) or deletion of the maternal ICR abrogated this
      association and altered Wsb1/Nf1 gene expression. These findings demonstrate that
      CTCF mediates an interchromosomal association, perhaps by directing distant DNA
      segments to a common transcription factory, and the data provide a model for long
      range allele-specific associations between gene regions on different chromosomes
      that suggest a framework for DNA recombination and RNA trans-splicing.

PMID- 16614225
TI  - Conformational switches modulate protein interactions in peptide antibiotic
      synthetases.
AB  - Protein dynamics plays an important role in protein function. Many functionally
      important motions occur on the microsecond and low millisecond time scale and can
      be characterized by nuclear magnetic resonance relaxation experiments. We
      describe the different states of a peptidyl carrier protein (PCP) that play a
      crucial role in its function as a peptide shuttle in the nonribosomal peptide
      synthetases of the tyrocidine A system. Both apo-PCP (without the bound 4'
      phosphopantetheine cofactor) and holo-PCP exist in two different stable
      conformations. We show that one of the apo conformations and one of the holo
      conformations are identical, whereas the two remaining conformations are only
      detectable by nuclear magnetic resonance spectroscopy in either the apo or holo
      form. We further demonstrate that this conformational diversity is an essential
      prerequisite for the directed movement of the 4'-PP cofactor and its interaction
      with externally acting proteins such as thioesterases and 4'-PP transferase.

PMID- 16614226
TI  - A common genetic variant is associated with adult and childhood obesity.
AB  - Obesity is a heritable trait and a risk factor for many common diseases such as
      type 2 diabetes, heart disease, and hypertension. We used a dense whole-genome
      scan of DNA samples from the Framingham Heart Study participants to identify a
      common genetic variant near the INSIG2 gene associated with obesity. We have
      replicated the finding in four separate samples composed of individuals of
      Western European ancestry, African Americans, and children. The obesity
      predisposing genotype is present in 10% of individuals. Our study suggests that
      common genetic polymorphisms are important determinants of obesity.

PMID- 16614227
TI  - Outcome of patients with HER2-positive advanced breast cancer progressing during
      trastuzumab-based therapy.
AB  - We sought to describe patterns of treatment and clinical outcome in patients with
      HER2-positive advanced breast cancer progressing on trastuzumab-based therapy.
      One hundred eighty-four consecutive HER2-positive advanced breast cancer patients
      received trastuzumab-based therapy between September 1999 and September 2004.
      Patients were followed up until death or May 2005. For patients progressing on
      trastuzumab-based therapy, we calculated the response rate (RR) to the first post
      progression treatment, overall survival (OS) from the first administration of
      trastuzumab, time to second progression (TT-SP), and post-progression survival
      (PPS), according to treatment. At the time of this analysis, 132 patients had
      progressed on trastuzumab-based therapy, and 89 had died. Of the progressing
      patients, 21 experienced rapid progression and could not receive additional
      anticancer treatments;40 patients continued trastuzumab either alone (12 patients
      with isolated central nervous system progression), with chemotherapy (23
      patients), or with endocrine therapy (5 patients); and 71 stopped trastuzumab and
      received chemotherapy (61 patients) or endocrine therapy (10 patients) as the
      first post-progression treatment. Excluding patients with rapid progression,
      clinical outcomes were similar whether trastuzumab was continued or not, in terms
      of RR (18% and 27%, respectively), OS (31 and 30 months, respectively), TT-SP (6
      and 7 months, respectively), and PPS (21 and 19 months, respectively). The
      clinical outcome of patients with HER2-positive advanced breast cancer
      progressing during trastuzumab-based therapy might not be influenced by
      continuing trastuzumab. The optimal therapeutic strategy in this setting of
      patients needs evaluation in randomized trials.

PMID- 16614228
TI  - Capecitabine monotherapy: safe and effective treatment for metastatic breast
      cancer.
AB  - Optimal management for metastatic breast cancer frequently involves cytotoxic
      chemotherapy. Over the years, several complex multidrug regimens have been
      developed that were based upon a rationale of synergistic antitumor activity and
      nonoverlapping toxicities. However, recently the clinical value of these complex
      regimens has been called into question as several drugs used alone (monotherapy)
      or in sequence (serial single agent) have been shown to be both efficacious and
      better tolerated. Capecitabine (an orally administered fluoropyrimidine
      carbamate) is one such agent that has been proven to be effective when used alone
      for metastatic breast cancer, metastatic colorectal cancer, and adjuvant colon
      cancer. In this review, published (or reported in abstract form) data examining
      various aspects of clinical response and tolerability with single-agent
      capecitabine for (primarily) first- and second-line metastatic breast cancer are
      examined. For the most part, response rates are comparable with those of the more
      complex regimens. Dose reductions from the labeled dose of 1,250 mg/m(2) twice
      daily are relatively common. Toxicities (following dose reductions if needed) are
      generally manageable, even by more frail patients. Elderly patients are more
      likely to have impaired renal function or be receiving warfarin treatment, and
      special attention to these factors is warranted. Nonetheless, the drug
      administered alone is a reasonable choice when single-agent chemotherapy is
      entertained as a treatment option for metastatic breast cancer, including in the
      first-line setting.

PMID- 16614229
TI  - Pegylated liposomal doxorubicin consolidation therapy after platinum/paclitaxel
      based chemotherapy for suboptimally debulked, advanced-stage epithelial ovarian
      cancer patients.
AB  - OBJECTIVE: To assess the feasibility of using pegylated liposomal doxorubicin
      (PLD) as a consolidation therapy in patients with advanced ovarian cancer who
      have attained a clinically defined complete response to initial
      platinum/paclitaxel-based chemotherapy. METHODS: Patients diagnosed with
      suboptimally debulked stage IIIC/IV epithelial ovarian cancer who attained a
      clinically defined complete response at the completion of platinum/paclitaxel
      based chemotherapy were eligible for this protocol. Patients were treated with
      PLD at a dose of 40 mg/m(2) every 28 days for four cycles. A survival analysis
      was calculated using the Kaplan-Meier method. RESULTS: Of the 30 patients
      enrolled, 29 were evaluable. Twenty-three patients (79%) completed all four
      cycles of consolidation therapy. Palmar-plantar erythrodysesthesia was the most
      common toxicity. Six patients remained clinically without evidence of disease
      with a median follow-up of 35 months from the completion of primary chemotherapy.
      The median progression-free interval was 15 months, and median overall survival
      time was 31 months, with 47% of patients achieving a 4-year survival.
      CONCLUSIONS: Consolidation therapy with PLD chemotherapy administered to women
      with advanced epithelial ovarian cancer after initial chemotherapy appears
      feasible based on its toxicity profile. Considering the tolerability of this
      agent, further investigation is needed to depict the optimal dose and schedule
      needed for consolidation therapy.

PMID- 16614231
TI  - Clinical implications of EGFR expression in the development and progression of
      solid tumors: focus on non-small cell lung cancer.
AB  - Dysregulation of the epidermal growth factor receptor (EGFR) signaling pathway is
      associated with the development and progression of malignancy, and EGFR-targeted
      therapies offer the promise of better treatment for many types of solid tumors,
      including non-small cell lung cancer. Anti-EGFR agents include monoclonal
      antibodies (mAbs) targeting the EGFR extracellular receptor domain and small
      molecule tyrosine kinase inhibitors (TKIs) targeting the EGFR intracellular
      kinase domain. Both mAbs and TKIs have demonstrated encouraging results as
      monotherapies and in combination with chemotherapy and radiotherapy. This review
      provides a critical update on the status of these novel therapeutics.

PMID- 16614232
TI  - Introduction to a special series of unique entities within the spectrum of large
      cell lymphoma.

PMID- 16614233
TI  - Burkitt's lymphoma: clinicopathologic features and differential diagnosis.
AB  - Burkitt's lymphoma is a highly aggressive lymphoma identified and described in
      the last century by Denis Burkitt in Africa, in areas endemic for malaria. Since
      its description in African children, it has been recognized outside areas with
      endemic malaria, frequently also in children as well as among individuals with an
      underlying immunodeficiency. Since its initial designation as Burkitt's lymphoma,
      this type of lymphoma and lymphomas closely resembling it have received a variety
      of names in different classifications of lymphomas and leukemias:
      undifferentiated lymphoma, Burkitt's and non-Burkitt's type in the modified
      Rappaport Classification, malignant lymphoma, small non-cleaved cell, Burkitt's
      type in the Working Formulation, Burkitt's lymphoma and high-grade B-cell
      lymphoma, Burkitt-like in the REAL Classification, and acute lymphoblastic
      leukemia, L3 type in the FAB Classification. With the publication of the WHO
      Classification of Haematopoietic and Lymphoid Tumors, the nomenclature of this
      lymphoma has come full circle, and it is once again known simply as Burkitt's
      lymphoma. In recent years, efforts have focused on improving therapy for this
      rapidly proliferating neoplasm while minimizing, to the extent possible,
      treatment-associated toxicity. These efforts have led to the development of high
      intensity, short-duration combination chemotherapy that has proven extremely
      effective for a high proportion of Burkitt's lymphoma patients. The differential
      diagnosis of Burkitt's lymphoma is broad, and precise diagnosis based on
      histologic, immunophenotypic, and genetic features remains the critical first
      step in planning appropriate therapy.

PMID- 16614234
TI  - T-cell/histiocyte-rich B-cell lymphoma: biology, diagnosis, and management.
AB  - T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) is an uncommon morphologic
      variant of diffuse large B-cell lymphoma (DLBCL). Pathologically, it is
      distinguished by <10% malignant B cells amid a majority population of reactive T
      lymphocytes and histiocytes. Diagnosis of this entity is occasionally difficult,
      as it may appear similar to other lymphoid diseases, such as nodular lymphocyte
      predominant Hodgkin's lymphoma and classic Hodgkin's lymphoma. Accurate diagnosis
      therefore rests with careful immunohistochemical analysis of the tumor cells and
      the inflammatory microenvironment. Clinically, T/HRBCL occurs in younger
      patients, predominantly affects men, and involves the liver, spleen, and bone
      marrow with greater frequency than traditional DLBCL. Despite the unique clinical
      features and robust host inflammatory response, T/HRBCL follows a natural history
      similar to those of other DLBCLs and responds similarly to therapy. Recent gene
      expression analysis demonstrates that a productive relationship with the host
      immune response may extend beyond this small DLBCL variant to include as many as
      one third of all DLBCLs. At present, T/HRBCL should be treated similarly to other
      stage-matched DLBCLs, though future therapies will likely be targeted at the
      relationship of the tumor cells with their inflammatory microenvironment.

PMID- 16614230
TI  - Chemotherapeutic approaches for targeting cell death pathways.
AB  - For several decades, apoptosis has taken center stage as the principal mechanism
      of programmed cell death in mammalian tissues. It also has been increasingly
      noted that conventional chemotherapeutic agents not only elicit apoptosis but
      other forms of nonapoptotic death such as necrosis, autophagy, mitotic
      catastrophe, and senescence. This review presents background on the signaling
      pathways involved in the different cell death outcomes. A re-examination of what
      we know about chemotherapy-induced death is vitally important in light of new
      understanding of nonapoptotic cell death signaling pathways. If we can precisely
      activate or inhibit molecules that mediate the diversity of cell death outcomes,
      perhaps we can succeed in more effective and less toxic chemotherapeutic
      regimens.

PMID- 16614235
TI  - The promise of the human papillomavirus vaccine does not confer immunity against
      ethical reflection.
AB  - The recent announcement of an experimental vaccine against human papillomavirus
      (HPV) has raised great hopes and expectations. Promising trial results, however,
      should not obscure ethical issues related to a vaccine's ultimate dissemination.
      Although lay media might view an HPV vaccine as a panacea, a more complicated
      ethical reality exists, touching upon public knowledge, health care disparities,
      and parental consent for childhood vaccination.

PMID- 16614236
TI  - TNF-alpha in cancer treatment: molecular insights, antitumor effects, and
      clinical utility.
AB  - Tumor necrosis factor alpha (TNF-alpha), isolated 30 years ago, is a
      multifunctional cytokine playing a key role in apoptosis and cell survival as
      well as in inflammation and immunity. Although named for its antitumor
      properties, TNF has been implicated in a wide spectrum of other diseases. The
      current use of TNF in cancer is in the regional treatment of locally advanced
      soft tissue sarcomas and metastatic melanomas and other irresectable tumors of
      any histology to avoid amputation of the limb. It has been demonstrated in the
      isolated limb perfusion setting that TNF-alpha acts synergistically with
      cytostatic drugs. The interaction of TNF-alpha with TNF receptor 1 and receptor 2
      (TNFR-1, TNFR-2) activates several signal transduction pathways, leading to the
      diverse functions of TNF-alpha. The signaling molecules of TNFR-1 have been
      elucidated quite well, but regulation of the signaling remains unclear. Besides
      these molecular insights, laboratory experiments in the past decade have shed
      light upon TNF-alpha action during tumor treatment. Besides extravasation of
      erythrocytes and lymphocytes, leading to hemorrhagic necrosis, TNF-alpha targets
      the tumor-associated vasculature (TAV) by inducing hyperpermeability and
      destruction of the vascular lining. This results in an immediate effect of
      selective accumulation of cytostatic drugs inside the tumor and a late effect of
      destruction of the tumor vasculature. In this review, covering TNF-alpha from the
      molecule to the clinic, we provide an overview of the use of TNF-alpha in cancer
      starting with molecular insights into TNFR-1 signaling and cellular mechanisms of
      the antitumor activities of TNF-alpha and ending with clinical response. In
      addition, possible factors modulating TNF-alpha actions are discussed.

PMID- 16614238
TI  - The molecular perspective: estrogen sulfotransferase.

PMID- 16614237
TI  - Darbepoetin alfa administered every three weeks is effective for the treatment of
      chemotherapy-induced anemia.
AB  - Patients with cancer receiving chemotherapy often have chemotherapy-induced
      anemia (CIA) and reduced quality of life. Darbepoetin alfa can effectively treat
      CIA when administered at an extended dosing interval of once every 3 weeks (Q3W).
      Darbepoetin alfa administered Q3W may allow synchronization of darbepoetin alfa
      therapy with chemotherapy administered Q3W. This multicenter, open-label, 16-week
      study evaluated the effectiveness and safety of darbepoetin alfa administered as
      a fixed dose (300 mug) Q3W in patients with CIA. Eligible patients (> or =18
      years) were anemic (hemoglobin <11g/dl), had a nonmyeloid malignancy, and were
      receiving multicycle chemotherapy. This analysis includes 1,493 patients who
      received at least one dose of darbepoetin alfa. The effect of baseline hemoglobin
      (<10 or > or =10 g/dl) on clinical outcomes was evaluated. Patients in the > or
      =10-g/dl stratum achieved the hemoglobin target range (11-13 g/dl)in less time
      than patients in the <10-g/dlstratum (3 weeks vs. 9 weeks). More patients in the
      > or =10-g/dl stratum achieved the hemoglobin target range (87% vs. 66%);
      however, similar proportions of patients in both strata maintained hemoglobin
      within the target range (73% vs. 71%). Fewer patients in the > or =10-g/dl
      stratum received RBC transfusions from week 5 to the end of the study (12% vs.
      28%). Over 50% of patients in both strata reported clinically significant
      improvements (> or =3-point increase) in Functional Assessment of Cancer Therapy
      Fatigue score. Twenty-eight percent of patients reported serious adverse events;
      3% of all patients had a venous or arterial thrombotic event. This study
      demonstrates that darbepoetin alfa Q3W is well tolerated and effective for
      treating CIA.

PMID- 16614239
TI  - Unique effects of Stat3 on the early phase of hematopoietic stem cell
      regeneration.
AB  - Self-renewal of hematopoietic stem cells (HSCs) is key to their reconstituting
      ability, but the signaling pathways that regulate this process remain poorly
      understood. Here we show that transduction of adult mouse bone marrow cells with
      a constitutively activated form of Stat3 (Stat3-C) increased their regenerative
      activity in lethally irradiated recipients. Conversely, transduction of these
      cells with a dominant-negative form of Stat3 suppressed their regenerative
      activity. Serial transplantation and clonal tracking of the HSC progeny
      regenerated in vivo from STAT3-C-transduced HSCs demonstrated that the major
      effect of forced expression of STAT3-C was to enhance HSC self-renewal during the
      initial phase of hematopoietic recovery. This acquired potential for enhanced
      self-renewal divisions then became latent, but was reactivated when the cells
      were transferred to new irradiated recipients. Increased levels of activated
      STAT3 were also found to be associated with greater preservation of primitive
      hematopoietic cells in short-term cultures. These results indicate a novel
      biphasic regulation of HSC self-renewal in vivo in which activated STAT3 promotes
      HSC self-renewal under stimulated, but not homeostatic, conditions. STAT3 may
      thus be an important regulator of hematopoietic regeneration and a novel target
      for HSC engineering.

PMID- 16614241
TI  - Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be
      associated with clinical resistance to the Abl kinase inhibitor nilotinib
      (AMN107).
AB  - In advanced-phase chronic myeloid leukemia (CML), resistance to imatinib mesylate
      is associated with point mutations in the BCR-ABL kinase domain. A new generation
      of potent ABL kinase inhibitors is undergoing clinical evaluation. It is
      important to generate specific resistance profiles for each of these compounds,
      which could translate into combinatorial and sequential treatment strategies.
      Having characterized nilotinib (AMN107) against a large panel of imatinib
      mesylate-resistant Bcr-Abl mutants, we investigated which mutants might arise
      under nilotinib therapy using a cell-based resistance screen. In contrast to
      imatinib mesylate, resistance to nilotinib was associated with a limited spectrum
      of Bcr-Abl kinase mutations. Among these were mutations affecting the P-loop and
      T315I. Rarely emerging resistant colonies at a concentration of 400 nM nilotinib
      exclusively expressed the T315I mutation. With the exception of T315I, all of the
      mutations that were identified were effectively suppressed when the nilotinib
      concentration was increased to 2000 nM, which falls within the peak-trough range
      in plasma levels (3.6-1.7 microM) measured in patients treated with 400 mg twice
      daily. Our findings suggest that nilotinib might be superior to imatinib mesylate
      in terms of the development of resistance. However, our study indicates that
      clinical resistance to nilotinib may be associated with the predominant emergence
      of T315I.

PMID- 16614242
TI  - Prospective simultaneous quantification of human cytomegalovirus-specific CD4+
      and CD8+ T-cell reconstitution in young recipients of allogeneic hematopoietic
      stem cell transplants.
AB  - We investigated immune reconstitution against human cytomegalovirus (HCMV) in 57
      hematopoietic stem cell transplant (HSCT) recipients, aged 1 to 24 years, through
      a novel method combining T-cell stimulation by HCMV-infected autologous dendritic
      cells with simultaneous cytometric quantification of HCMV-specific, IFNgamma
      producing CD4(+) and CD8(+) T cells. Lymphoproliferative response (LPR) to HCMV
      antigens was also determined. Patients were stratified into 2 groups according to
      HCMV serostatus, comprising 39 HCMV-seropositive (R(+)) and 18 HCMV-seronegative
      (R(-)) patients who received a transplant from a sero-positive donor. Recovery of
      both HCMV-specific CD4(+) and CD8(+) T-cell immunity occurred in all 39 R(+)
      patients within 6 months and in 6 (33%) of 18 R(-) patients within 12 months. In
      R(+) patients, the median numbers of HCMV-specific CD8(+) and CD4(+)T cells were
      significantly higher than those of healthy controls, starting from days +60 and
      +180, respectively. In (R-) patients, the median numbers of HCMV-specific T cells
      were consistently lower than in R(+) patients. LPR was delayed compared with
      reconstitution of IFNgamma-producing T cells. Patients with delayed specific
      immune reconstitution experienced recurrent episodes of HCMV infection. HCMV
      seropositivity of young HSCT recipients is the major factor responsible for HCMV
      specific immune reconstitution, irrespective of donor serostatus, and measurement
      of HCMV-specific T cells appears useful for correct management of HCMV infection.

PMID- 16614244
TI  - Competition within the early B-cell compartment conditions B-cell reconstitution
      after hematopoietic stem cell transplantation in nonirradiated recipients.
AB  - Severe combined immunodeficiency (SCID) is characterized by a complete block in T
      lymphocyte differentiation. Most SCID also affects B-cell development or
      function, although a normal pool of pro-B cells is detectable. Treatment of SCID
      consists of allogeneic hematopoietic stem cell transplantation (HSCT), but in the
      absence of a myeloablative conditioning regimen, only T cells, and in some cases,
      natural killer (NK) cells, are of donor origin, while all other leukocytes
      subsets are of host origin. We hypothesized that donor B-cell development success
      could be conditioned by the competitive ability of recipient B-cell precursors in
      the bone marrow. We therefore compared the outcome of unconditioned HSCT in mice
      that differed with respect to their pro-B-cell compartments. B-cell
      reconstitution was limited in recipient mice containing a normal pro-B-cell pool,
      whereas immature and mature B-cell numbers reached wild-type levels in mice with
      compromised early B-cell precursors. Interestingly, host NK cells did not modify
      the outcome of unconditioned HSCT as long as the early B-cell compartment was
      compromised. These observations suggest that recipient B-cell precursors
      condition the reconstitution of the donor B-cell pool and, if extrapolative to
      humans, suggest that conditioning regimens targeting host pro-B cells may help
      improve B-cell reconstitution after allogeneic HSCT.

PMID- 16614245
TI  - Activating NOTCH1 mutations predict favorable early treatment response and long
      term outcome in childhood precursor T-cell lymphoblastic leukemia.
AB  - Activating mutations of the transmembrane receptor NOTCH1 are common in precursor
      T-cell lymphoblastic leukemia (T-ALL). We systematically analyzed the impact of
      activating NOTCH1 mutations on early treatment response and long-term outcome in
      157 patients with T-ALL of the pediatric ALL-Berlin-Frankfurt-Munster (BFM) 2000
      study. We confirm previous results that NOTCH1 mutations occur in more than 50%
      of T-ALL in children. In 82 patients (82/157; 52.2%), activating NOTCH1 mutations
      were identified either in the heterodimerization (55/82; 67.1%), in the PEST
      (13/82; 15.9%), or in both domains (14/82; 17.0%). The presence of NOTCH1
      mutations was significantly correlated with a good prednisone response and
      favorable minimal residual disease (MRD) kinetics, which was independent from
      sex, age, white blood cell count, and T-cell immunophenotype at the time of
      diagnosis. Furthermore, activating NOTCH1 mutations specified a large subgroup of
      patients with an excellent prognosis. These findings indicate that in the context
      of the ALL-BFM 2000 treatment strategy, NOTCH1 mutations predict a more rapid
      early treatment response and a favorable long-term outcome in children with T
      ALL.

PMID- 16614246
TI  - The apoptotic-cell receptor CR3, but not alphavbeta5, is a regulator of human
      dendritic-cell immunostimulatory function.
AB  - Dendritic cells (DCs) that capture apoptotic cells (ACs) in the steady state
      mediate peripheral tolerance to self-antigens. ACs are recognized by an array of
      receptors on DCs, the redundancy of which is not completely defined. We made use
      of an AC surrogate system to address the individual roles of the alphavbeta5 and
      complement receptors (CRs) in the phagocytosis and induction of immunity. CR3 and
      CR4, while substantially less efficient than alphavbeta5 in internalizing ACs,
      initiate signals that render DCs tolerogenic. Responding T cells show impaired
      proliferation and IFNgamma production and subsequently die by apoptosis. While
      tolerogenic DCs are not induced via alphavbeta5, coligation of CR3 and
      alphavbeta5 maintains the DC's tolerogenic profile. This immunomodulatory role,
      however, is countered by a significant inflammatory stimulus such as bacterial
      infection. Overall, our data suggest that under steady-state conditions,
      signaling via CRs predominates to render DCs tolerogenic.

PMID- 16614247
TI  - Aberrant somatic hypermutation in tumor cells of nodular-lymphocyte-predominant
      and classic Hodgkin lymphoma.
AB  - Aberrant somatic hypermutation (SHM) has been identified as a mechanism for
      genomewide instability in diffuse large B-cell lymphoma (DLBCL). To assess
      whether aberrant SHM plays a role in the molecular pathogenesis of Hodgkin
      lymphoma (HL), we investigated microdissected neoplastic cells of nodular
      lymphocyte-predominant HL (NLPHL; n = 10) and classic HL (cHL; n = 9) for the
      presence of mutations in the 5' sequences of 4 previously identified aberrant SHM
      targets (PIM1, PAX5, RhoH/TTF, c-MYC). Mutations in one or more genes were
      detected in 80% of NLPHLs and 55% of cHLs, with 50% and 30% of patients carrying
      mutations in 2 or more genes, respectively. The most frequently involved
      protooncogene was PAX5, mutated in 7 of 9 patients with NLPHL and 2 of 9 patients
      with cHL. In total, 34 mutations were detected in NLPHL (frequency, 1.04/1,000
      bp) and 35 were detected in patients with cHL (frequency, 1.92/1,000 bp).
      Mutations were of somatic origin because they were absent in control T cells and
      shared most of the features of the immunoglobulin variable (IGV) gene-associated
      SHM mechanism-ie, single nucleotide substitutions (n = 63) with rare
      deletions/insertions (n = 6) and a predominance of transitions over transversions
      with preferential targeting motifs. Our finding that NLPHL and cHL are targeted
      by aberrant SHM, as is DLBCL, suggests that these lymphomas may share common
      molecular pathogenetic events.

PMID- 16614248
TI  - Molecular strategies for detection and quantitation of clonal cytotoxic T-cell
      responses in aplastic anemia and myelodysplastic syndrome.
AB  - Immune mechanisms are involved in the pathophysiology of aplastic anemia (AA) and
      myelodysplastic syndrome (MDS). Immune inhibition can result from cytotoxic T
      cell (CTL) attack against normal hematopoiesis or reflect immune surveillance. We
      used clonally unique T-cell receptor (TCR) variable beta-chain (VB) CDR3 regions
      as markers of pathogenic CTL responses and show that while marrow failure
      syndromes are characterized by polyclonal expansions, overexpanded clones exist
      in these diseases and can serve as investigative tools. To test the applicability
      of clonotypic assays, we developed rational molecular methods for the detection
      of immunodominant clonotypes in blood and in historic marrow biopsies of 35 AA,
      37 MDS, and 21 paroxysmal nocturnal hemoglobinuria (PNH) patients, in whom
      specific CDR3 sequences and clonal sizes were determined. CTL expansions were
      detected in 81% and 97% of AA and MDS patients, respectively. In total, 81
      immunodominant signature clonotypes were identified. Based on the sequence of
      immunodominant CDR3 clonotypes, we designed quantitative assays for monitoring
      corresponding clones, including clonotypic Taqman polymerase chain reaction (PCR)
      and clonotype-specific sequencing. No correlation was found between clonality and
      disease severity but in patients treated with immunosuppression, truly pathogenic
      clones were identified based on the decline that paralleled hematologic response.
      We conclude that immunodominant clonotypes associated with marrow failure may be
      used to monitor immunosuppressive therapy.

PMID- 16614250
TI  - Pathogenic potential of novel Chlamydiae and diagnostic approaches to infections
      due to these obligate intracellular bacteria.
AB  - Novel chlamydiae are newly recognized members of the phylum Chlamydiales that are
      only distantly related to the classic Chlamydiaceae, i.e., Chlamydia and
      Chlamydophila species. They also exhibit an obligate biphasic intracellular life
      cycle within eukaryote host cells. Some of these new chlamydiae are currently
      considered potential emerging human and/or animal pathogens. Parachlamydia
      acanthamoebae and Simkania negevensis are both emerging respiratory human
      pathogens, Waddlia chondrophila could be a novel abortigenic bovine agent, and
      Piscichlamydia salmonis has recently been identified as an agent of the gill
      epitheliocystis in the Atlantic salmon. Fritschea spp. and Rhabdochlamydia spp.
      seem to be confined to arthropods, but some evidence for human exposure exists.
      In this review, we first summarize the data supporting a pathogenic potential of
      the novel chlamydiae for humans and other vertebrates and the interactions that
      most of these chlamydiae have with free-living amoebae. We then review the
      diagnostic approaches to infections potentially due to the novel chlamydiae,
      especially focusing on the currently available PCR-based protocols, mammalian
      cell culture, the amoebal coculture system, and serology.

PMID- 16614249
TI  - Clinical and laboratory features of the Nocardia spp. based on current molecular
      taxonomy.
AB  - The recent explosion of newly described species of Nocardia results from the
      impact in the last decade of newer molecular technology, including PCR
      restriction enzyme analysis and 16S rRNA sequencing. These molecular techniques
      have revolutionized the identification of the nocardiae by providing rapid and
      accurate identification of recognized nocardiae and, at the same time, revealing
      new species and a number of yet-to-be-described species. There are currently more
      than 30 species of nocardiae of human clinical significance, with the majority of
      isolates being N. nova complex, N. abscessus, N. transvalensis complex, N.
      farcinica, N. asteroides type VI (N. cyriacigeorgica), and N. brasiliensis. These
      species cause a wide variety of diseases and have variable drug susceptibilities.
      Accurate identification often requires referral to a reference laboratory with
      molecular capabilities, as many newer species are genetically distinct from
      established species yet have few or no distinguishing phenotypic characteristics.
      Correct identification is important in deciding the clinical relevance of a
      species and in the clinical management and treatment of patients with nocardial
      disease. This review characterizes the currently known pathogenic species of
      Nocardia, including clinical disease, drug susceptibility, and methods of
      identification.

PMID- 16614251
TI  - Laboratory diagnostics of botulism.
AB  - Botulism is a potentially lethal paralytic disease caused by botulinum
      neurotoxin. Human pathogenic neurotoxins of types A, B, E, and F are produced by
      a diverse group of anaerobic spore-forming bacteria, including Clostridium
      botulinum groups I and II, Clostridium butyricum, and Clostridium baratii. The
      routine laboratory diagnostics of botulism is based on the detection of botulinum
      neurotoxin in the patient. Detection of toxin-producing clostridia in the patient
      and/or the vehicle confirms the diagnosis. The neurotoxin detection is based on
      the mouse lethality assay. Sensitive and rapid in vitro assays have been
      developed, but they have not yet been appropriately validated on clinical and
      food matrices. Culture methods for C. botulinum are poorly developed, and
      efficient isolation and identification tools are lacking. Molecular techniques
      targeted to the neurotoxin genes are ideal for the detection and identification
      of C. botulinum, but they do not detect biologically active neurotoxin and should
      not be used alone. Apart from rapid diagnosis, the laboratory diagnostics of
      botulism should aim at increasing our understanding of the epidemiology and
      prevention of the disease. Therefore, the toxin-producing organisms should be
      routinely isolated from the patient and the vehicle. The physiological group and
      genetic traits of the isolates should be determined.

PMID- 16614252
TI  - The front line of enteric host defense against unwelcome intrusion of harmful
      microorganisms: mucins, antimicrobial peptides, and microbiota.
AB  - The intestinal tract is a complex ecosystem that combines resident microbiota and
      the cells of various phenotypes with complex metabolic activities that line the
      epithelial wall. The intestinal cells that make up the epithelium provide
      physical and chemical barriers that protect the host against the unwanted
      intrusion of microorganisms that hijack the cellular molecules and signaling
      pathways of the host and become pathogenic. Some of the organisms making up the
      intestinal microbiota also have microbicidal effects that contribute to the
      barrier against enteric pathogens. This review describes the two cell lineages
      present in the intestinal epithelium: the goblet cells and the Paneth cells, both
      of which play a pivotal role in the first line of enteric defense by producing
      mucus and antimicrobial peptides, respectively. We also analyze recent insights
      into the intestinal microbiota and the mechanisms by which some resident species
      act as a barrier to enteric pathogens. Moreover, this review examines whether the
      cells producing mucins or antimicrobial peptides and the resident microbiota act
      in partnership and whether they function individually and/or synergistically to
      provide the host with an effective front line of defense against harmful enteric
      pathogens.

PMID- 16614254
TI  - Clinically relevant chromosomally encoded multidrug resistance efflux pumps in
      bacteria.
AB  - Efflux pump genes and proteins are present in both antibiotic-susceptible and
      antibiotic-resistant bacteria. Pumps may be specific for one substrate or may
      transport a range of structurally dissimilar compounds (including antibiotics of
      multiple classes); such pumps can be associated with multiple drug (antibiotic)
      resistance (MDR). However, the clinical relevance of efflux-mediated resistance
      is species, drug, and infection dependent. This review focuses on chromosomally
      encoded pumps in bacteria that cause infections in humans. Recent structural data
      provide valuable insights into the mechanisms of drug transport. MDR efflux pumps
      contribute to antibiotic resistance in bacteria in several ways: (i) inherent
      resistance to an entire class of agents, (ii) inherent resistance to specific
      agents, and (iii) resistance conferred by overexpression of an efflux pump.
      Enhanced efflux can be mediated by mutations in (i) the local repressor gene,
      (ii) a global regulatory gene, (iii) the promoter region of the transporter gene,
      or (iv) insertion elements upstream of the transporter gene. Some data suggest
      that resistance nodulation division systems are important in pathogenicity and/or
      survival in a particular ecological niche. Inhibitors of various efflux pump
      systems have been described; typically these are plant alkaloids, but as yet no
      product has been marketed.

PMID- 16614257
TI  - HIV regulation of the IL-7R: a viral mechanism for enhancing HIV-1 replication in
      human macrophages in vitro.
AB  - We report a novel mechanism, involving up-regulation of the interleukin (IL)-7
      cytokine receptor, by which human immunodeficiency virus (HIV) enhances its own
      production in monocyte-derived macrophages (MDM) in vitro. HIV-1 infection or
      treatment of MDM cultures with exogenous HIV-1 Tat(86) protein up-regulates the
      IL-7 receptor (IL-7R) alpha-chain at the levels of steady-state RNA, protein, and
      functional IL-7R on the cell surface (as measured by ligand-induced receptor
      signaling). This IL-7R up-regulation is associated with increased amounts of HIV
      1 virions in the supernatants of infected MDM cultures treated with exogenous IL
      7 cytokine. The overall effect of IL-7 stimulation on HIV replication in MDM
      culture supernatants is typically in the range of one log and greater. The
      results are consistent with a model in which HIV infection produces the Tat
      protein, which in turn up-regulates IL-7R in a paracrine manner. This results in
      increased IL-7R signaling in response to the IL-7 cytokine, which ultimately
      promotes early events in HIV replication, including binding/entry and possibly
      other steps prior to reverse transcription. The results suggest that the effects
      of IL-7 on HIV replication in MDM should be considered when analyzing and
      designing clinical trials involving treatment of patients with IL-7 or Tat
      vaccines.

PMID- 16614256
TI  - Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for
      the future of antifungal susceptibility testing.
AB  - Developing interpretive breakpoints for any given organism-drug combination
      requires integration of the MIC distribution, pharmacokinetic and pharmacodynamic
      parameters, and the relationship between in vitro activity and outcome from both
      in vivo and clinical studies. Previously, the Subcommittee for Antifungal Testing
      of the Clinical and Laboratory Standards Institute (CLSI [formerly National
      Committee for Clinical Laboratory Standards]) proposed MIC interpretive
      breakpoints for fluconazole and Candida spp. These breakpoints were considered to
      be somewhat weak, because the clinical data supporting them came largely from
      mucosal infections and there were very few infections involving strains with
      elevated fluconazole MICs. We readdress the issue of fluconazole breakpoints for
      Candida by using published clinical and microbiologic data to provide further
      validation of the breakpoints proposed by the CLSI in 1997. We also address
      interpretive breakpoints for agar disk diffusion testing of fluconazole. The MIC
      distribution for fluconazole was determined with a collection of 13,338 clinical
      isolates. The overall MIC at which 90% of the isolates were inhibited was 8
      microg/ml: 91% were susceptible (S) at a MIC of <or=8 microg/ml and 3% were
      resistant (R) (MIC >or= 64 microg/ml). Similar results were obtained for 2,190
      isolates from randomized clinical trials. Analysis of available data for 1,295
      patient-episode-isolate events (692 represented mucosal infections and 603
      represented invasive infections) from 12 published clinical studies demonstrated
      an overall success rate of 77%, including 85% for those episodes in which the
      fluconazole MIC was <or=8 microg/ml, 67% for those episodes in which the MIC was
      16 to 32 microg/ml, and 42% for those episodes with resistant (MIC >or= 64
      microg/ml) isolates. Pharmacodynamic analysis demonstrated a strong relationship
      between MIC, fluconazole dose, and outcome. A dose/MIC ratio of approximately 25
      was supportive of the following susceptibility breakpoints for fluconazole and
      Candida spp.: S, MIC <or= 8 microg/ml; susceptible-dose dependent (SDD), MIC = 16
      to 32 microg/ml; R, MIC >or= 64 microg/ml. The corresponding disk test
      breakpoints are as follows: S, >or=19 mm; SDD, 15 to 18 mm; R, <or=14 mm.

PMID- 16614258
TI  - Mixed Langerhans cell and interstitial/dermal dendritic cell subsets emanating
      from monocytes in Th2-mediated inflammatory conditions respond differently to
      proinflammatory stimuli.
AB  - The skin harbors two dendritic cell (DC) subsets, Langerhans cells (LC) and
      interstitial/dermal DC (IDDC), which traffic to lymph nodes after inflammation
      and ultraviolet stress. To demonstrate that monocytes may act as DC precursors
      for skin DC in postinflammatory recolonization, we generated LC and IDDC from
      monocytes by using cytokines related to the T helper cell type 2 environment
      [granulocyte macrophage-colony stimulating factor/transforming growth factor
      beta/interleukin-13/tumor necrosis factor alpha (GM-CSF/TGF-beta/IL-13/TNF
      alpha)]. In this study, skin DC [LC as Langerin/CD207(+) cells and IDDC as DC
      specific intercellular adhesion molecule-grabbing nonintegrin (SIGN)/CD209(+)
      cells] displayed desynchronized programs along their differentiation,
      activation/maturation processes in response to stimuli characteristics of a
      proinflammatory context. First, we demonstrate that monocytes are able to diverge
      simultaneously along two distinct pathways toward Langerin(+)-LC-type DC and DC
      SIGN(+)-IDDC. Second, as TGF-beta is known to antagonize the TNF-alpha-induced
      maturation process of DC, we showed that IDDC did not mature and acquired a low
      CC chemokine receptor 7 (CCR7) receptor expression even when stimulated with
      prolonged incubation with TNF-alpha. It is striking that the LC subset is able to
      express a high level of CCR7 expression and the maturation marker DC-lysosome
      associated membrane protein (DC-LAMP). Third, mixed LC and IDDC subsets secrete
      IL-10 and IL-12 when stimulated by CD40 ligand and lipopolysaccharide (LPS) but
      not after prolonged incubation with TNF-alpha. In contrast, LPS was a better
      activator of IL-10 secretion than the CD40 ligand for GM-CSF/IL-4-generated DC
      and for GM-CSF/TGF-beta/IL-13-generated LC and IDDC populations. To summarize,
      the phenotypic/migratory maturation status of LC may be more easily enhanced by
      stimuli mimicking a proinflammatory situation, and IDDC are more resistant.
      Moreover, our culture system provided a means of studying cross-talk between two
      skin DC outside of their respective skin compartment.

PMID- 16614253
TI  - The continuing challenges of leprosy.
AB  - Leprosy is best understood as two conjoined diseases. The first is a chronic
      mycobacterial infection that elicits an extraordinary range of cellular immune
      responses in humans. The second is a peripheral neuropathy that is initiated by
      the infection and the accompanying immunological events. The infection is curable
      but not preventable, and leprosy remains a major global health problem,
      especially in the developing world, publicity to the contrary notwithstanding.
      Mycobacterium leprae remains noncultivable, and for over a century leprosy has
      presented major challenges in the fields of microbiology, pathology, immunology,
      and genetics; it continues to do so today. This review focuses on recent advances
      in our understanding of M. leprae and the host response to it, especially
      concerning molecular identification of M. leprae, knowledge of its genome,
      transcriptome, and proteome, its mechanisms of microbial resistance, and
      recognition of strains by variable-number tandem repeat analysis. Advances in
      experimental models include studies in gene knockout mice and the development of
      molecular techniques to explore the armadillo model. In clinical studies, notable
      progress has been made concerning the immunology and immunopathology of leprosy,
      the genetics of human resistance, mechanisms of nerve injury, and chemotherapy.
      In nearly all of these areas, however, leprosy remains poorly understood compared
      to other major bacterial diseases.

PMID- 16614259
TI  - Evidence that phospholipase-C-dependent, calcium-independent mechanisms are
      required for directional migration of T-lymphocytes in response to the CCR4
      ligands CCL17 and CCL22.
AB  - Macrophage-derived chemokine [CC chemokine ligand 22 (CCL22)] and thymus- and
      activation-regulated chemokine (CCL17) mediate cellular effects, principally by
      binding to their receptor CC chemokine receptor 4 (CCR4) and together, constitute
      a multifunctional chemokine/receptor system with homeostatic and inflammatory
      roles within the body. This study demonstrates that CCL22 and CCL17 stimulate
      pertussis toxin-sensitive elevation of intracellular calcium in the CEM leukemic
      T cell line and human peripheral blood-derived T helper type 2 (Th2) cells.
      Inhibition of phospholipase C (PLC) resulted in the abrogation of chemokine
      mediated calcium mobilization. Chemokine-stimulated calcium responses were also
      abrogated completely by the inhibition of inositol 1,4,5-trisphosphate
      [Ins(1,4,5)P3] receptor-mediated calcium release. Chemotactic responses of CEM
      and human Th2 cells to CCL17 and CCL22 were similarly abrogated by inhibition of
      PLC and inhibition of novel, Ca2+-independent/diacylglycerol-dependent protein
      kinase C (PKC) isoforms. Inhibition of Ins(1,4,5)P3 receptor-mediated calcium
      release from intracellular stores had no effect on chemotactic responses to CCR4
      ligands. Taken together, this study provides compelling evidence of an important
      role for PLC and diacylglycerol-dependent effector mechanisms (most likely
      involving novel PKC isoforms) in CCL17- and CCL22-stimulated, directional cell
      migration. In this regard, CCL22 stimulates phosphatidylinositol-3 kinase
      independent phosphorylation of the novel delta isoform of PKC at threonine 505,
      situated within its activation loop--an event closely associated with increased
      catalytic activity.

PMID- 16614261
TI  - Review of the American Heart Association's guidelines for cardiovascular disease
      prevention in women.
AB  - Cardiovascular disease (CVD) is the leading cause of death of women in the United
      States and most of the developed world. The latest available data from the World
      Health Organization indicate that 16.6 million people around the globe die of CVD
      each year. World deaths from coronary heart disease (CHD) in 2002 totalled 7.2
      million. One in seven women in Europe will die of CHD; in the United Kingdom >
      1.2 million women are living with CHD. Despite advances in diagnosing and
      treating CHD, the disease accounts for the majority of CVD deaths in women in the
      United States, with more than 240,000 dying annually. Although coronary heart
      disease is the predominant cause of mortality for adult women in the United
      States, screening for coronary risk factors and coronary risk reduction
      interventions remains underused in women. In February of 2004, the American Heart
      Association published the first evidence-based guidelines for CVD prevention in
      women, consisting of a set of clinical recommendations tailored to a woman's
      individual level of risk.

PMID- 16614262
TI  - Gender and heart failure: a population perspective.

PMID- 16614264
TI  - Epidemiology of coronary heart disease in women.

PMID- 16614263
TI  - Coronary revascularisation in women.
AB  - Coronary heart disease is the leading cause of death in men and women worldwide.
      It is still considered a disease of men and there has been little recognition of
      its importance in women. Gender differences exist in acute and chronic ischaemia
      in terms of clinical manifestations, investigations and treatment. There are
      clear gender differences in coronary revascularisation with a higher mortality
      seen in women. At the time a woman presents with coronary artery disease she is
      older and has more co-morbid factors. Furthermore, women have smaller coronary
      arteries making them more difficult to revascularise. In recent years there has
      been a general trend towards improved outcomes in women undergoing both surgical
      and percutaneous coronary intervention. The increasing use of drug eluting stents
      and adjunctive medical treatment as well as the use of off-pump bypass surgery
      needs further evaluation in terms of gender differences. This article reviews the
      current literature on coronary revascularisation in women.

PMID- 16614255
TI  - Burn wound infections.
AB  - Burns are one of the most common and devastating forms of trauma. Patients with
      serious thermal injury require immediate specialized care in order to minimize
      morbidity and mortality. Significant thermal injuries induce a state of
      immunosuppression that predisposes burn patients to infectious complications. A
      current summary of the classifications of burn wound infections, including their
      diagnosis, treatment, and prevention, is given. Early excision of the eschar has
      substantially decreased the incidence of invasive burn wound infection and
      secondary sepsis, but most deaths in severely burn-injured patients are still due
      to burn wound sepsis or complications due to inhalation injury. Burn patients are
      also at risk for developing sepsis secondary to pneumonia, catheter-related
      infections, and suppurative thrombophlebitis. The introduction of silver
      impregnated devices (e.g., central lines and Foley urinary catheters) may reduce
      the incidence of nosocomial infections due to prolonged placement of these
      devices. Improved outcomes for severely burned patients have been attributed to
      medical advances in fluid resuscitation, nutritional support, pulmonary and burn
      wound care, and infection control practices.

PMID- 16614265
TI  - Risk factors for cardiovascular disease and hormone therapy in women.

PMID- 16614266
TI  - Cardiac syndrome X in women: the role of oestrogen deficiency.
AB  - Cardiac syndrome X (CSX), defined as typical exertional chest pain, a positive
      response to stress testing, and normal coronary arteriograms, encompasses
      different pathogenic subgroups. Both cardiac and non-cardiac mechanisms have been
      suggested to play a pathogenic role, and it has been shown that the syndrome is
      associated with myocardial ischaemia in at least a proportion of patients.
      Radionuclide myocardial perfusion defects, coronary sinus oxygen saturation
      abnormalities and pH changes, myocardial lactate production and stress-induced
      alterations of cardiac high energy phosphate have been reported in CSX patients,
      suggesting an ischaemic origin for their symptoms. Microvascular abnormalities
      often caused by endothelial dysfunction appear to be responsible for myocardial
      ischaemia in these patients. CSX is more prevalent in women than in men, and the
      majority of women with CSX are peri- or post-menopausal. Thus oestrogen
      deficiency has been suggested to have a pathogenic role in CSX. Additional
      factors such as abnormal pain perception may also contribute to the genesis of
      chest pain in patients with angina and normal coronary angiograms. The management
      of this syndrome is difficult because of the heterogeneity of pathogenic
      mechanisms and uncertainties as to its origin. This article discusses the problem
      of CSX in women, the potential pathogenic role of oestrogen deficiency, and
      practical clinical management.

PMID- 16614267
TI  - Images in cardiology. Double coarctation and double grafts: role of computed
      tomographic angiography in diagnosis of a clinic mystery.

PMID- 16614268
TI  - Computed tomographic coronary angiography: how many slices do you need?
AB  - While increasing the number of slices in multislice computed tomography clearly
      brings benefits in terms of detecting significant coronary disease, heavy
      calcification remains a problem, as does the high radiation burden.

PMID- 16614269
TI  - Stamps in cardiology. Artificial heart.

PMID- 16614270
TI  - Images in cardiology. Permanent pacemaker lead thrombosis leading to recurrent
      pulmonary embolism.

PMID- 16614271
TI  - Images in cardiology. Guidewire loss: mishap or blunder?

PMID- 16614272
TI  - Images in cardiology. Covering your mistakes: PTFE covered stents in iatrogenic
      coronary dissection.

PMID- 16614273
TI  - Images in cardiology. Left main coronary artery stenosis associated with aortitis
      in a patient with Crohn's disease.

PMID- 16614275
TI  - Images in cardiology. Congenital foramen of the left pericardium masquerading as
      left ventricular aneurysm.

PMID- 16614274
TI  - Economic evaluation of the impact of nicorandil in angina (IONA) trial.
AB  - OBJECTIVE: To estimate the net cost of adding nicorandil to usual treatment for
      patients with angina and to compare this with indicators of health benefit.
      DESIGN: Cost effectiveness analysis. SETTING: Based on results of the IONA
      (impact of nicorandil on angina) trial. PATIENTS: Patients with angina fulfilling
      the entry criteria for the IONA trial. INTERVENTIONS: In one arm of the trial
      nicorandil was added to existing antianginal treatment and compared with existing
      treatment alone. MAIN OUTCOME MEASURES: Costs were for use of hospital resources
      (for cardiovascular, cerebrovascular, and gastrointestinal reasons), nicorandil,
      and care after hospital discharge. Benefits were assessed in three ways: (1) IONA
      trial primary outcome (coronary heart disease (CHD) death, non-fatal myocardial
      infarction, or hospital admission for cardiac chest pain); (2) acute coronary
      syndrome (CHD death, non-fatal myocardial infarction, or unstable angina); and
      (3) event-free survivors at the end of the trial. RESULTS: The net cost for each
      additional IONA trial end point averted was -5 pounds sterling (-7 euros). The
      net cost for each case of acute coronary syndrome averted was -8 pounds sterling
      (-12 euros). The net cost for each event-free survivor was -5 pounds sterling (-7
      euros). These figures are based on gastrointestinal events that were judged
      definitely or probably related to nicorandil. When all gastrointestinal events
      were included these three ratios rose to 567 pounds sterling (835 euros), 886
      pounds sterling (1305 euros), and 516 pounds sterling (760 euros), respectively.
      CONCLUSIONS: A substantial amount of the additional cost of nicorandil is offset
      by reduced use of hospital services. The limited comparisons possible with other
      CHD interventions suggest that nicorandil compares favourably.

PMID- 16614276
TI  - Images in cardiology. Mid aortic syndrome: a rare cause of reversible
      cardiomyopathy.

PMID- 16614277
TI  - Images in cardiology. Unusual dominant course of left circumflex coronary artery
      with absent right coronary artery.

PMID- 16614278
TI  - Images in cardiology. Coronary angiography through the radial approach: passage
      through "Z" bend innominate artery.

PMID- 16614279
TI  - Images in cardiology. ECG showing features of total left main coronary artery
      occlusion.

PMID- 16614280
TI  - Images in cardiology. Unexpected response of saphenous vein graft occlusion to
      antiplatelet drugs.

PMID- 16614281
TI  - Detection of functional differences between different platelet membrane
      glycoprotein Ibalpha variable number tandem repeat and Kozak genotypes as shown
      by the PFA-100 system.

PMID- 16614282
TI  - Images in cardiology. Multiple complications of aortic valve endocarditis
      diagnosed from the ECG.

PMID- 16614283
TI  - Relation between birth weight and soluble markers of endothelial function in
      middle aged subjects.

PMID- 16614284
TI  - Beneficial effect of short term intake of red wine polyphenols on coronary
      microcirculation in patients with coronary artery disease.

PMID- 16614285
TI  - Association of serum soluble heat shock protein 60 with toll-like receptor 4
      polymorphism and severity of coronary artery disease.

PMID- 16614286
TI  - Images in cardiology. Fabry's disease, an X-linked recessive condition, can have
      isolated cardiac manifestations in heterozygote females.

PMID- 16614287
TI  - Congestive heart failure: extent of cardiac functional changes caused by aging
      and organ dysfunction.

PMID- 16614288
TI  - Images in cardiology. Cardiac sarcoidosis in a 60 year old woman.

PMID- 16614289
TI  - Myocardial perfusion by first pass contrast magnetic resonance: a robust method
      for quantitative regional assessment of perfusion reserve index.

PMID- 16614290
TI  - Hospital burden of suspected acute coronary syndromes: recent trends.

PMID- 16614291
TI  - Images in cardiology. Spontaneous healing of a severe coronary artery dissection.

PMID- 16614292
TI  - Usefulness of quantitative myocardial contrast echocardiography for prediction of
      ventricular function recovery after myocardial infarction treated with primary
      angioplasty.

PMID- 16614293
TI  - Images in cardiology. Thrombus at the junction of the inferior vena cava and
      right atrium: a contraindication for transfemoral percutaneous mitral
      commissurotomy.

PMID- 16614294
TI  - Undertreatment of coronary heart disease in patients undergoing coronary artery
      bypass surgery.

PMID- 16614295
TI  - Images in cardiology. Intramyocardial dissecting haemorrhage and multiple left
      ventricular thrombus formations in subacute myocardial infarction and
      antiphospholipid syndrome.

PMID- 16614296
TI  - Exercise and heart failure: assessment and treatment.

PMID- 16614297
TI  - Approach to wide complex tachycardias in patients without structural heart
      disease.

PMID- 16614298
TI  - Current perspectives in diastolic dysfunction and diastolic heart failure.

PMID- 16614299
TI  - Images in cardiology. Clenched fist appearance in endomyocardial fibrosis.

PMID- 16614300
TI  - BCS (British Cardiac Society) Annual Scientific Conference 2006, 24-27 April,
      Glasgow, Scotland, United Kingdom. Abstracts.

PMID- 16614302
TI  - Transgenic mice overexpressing the 5-hydroxytryptamine transporter gene in smooth
      muscle develop pulmonary hypertension.
AB  - One intrinsic abnormality of pulmonary artery smooth muscle cells (PA-SMCs) in
      human idiopathic pulmonary hypertension (iPH) is an exaggerated proliferative
      response to internalized serotonin (5-HT) caused by increased expression of the 5
      HT transporter (5-HTT). To investigate whether 5-HTT overexpression in PA-SMCs is
      sufficient to produce PH, we generated transgenic mice overexpressing 5-HTT under
      the control of the SM22 promoter. Studies in SM22-LacZ(+) mice showed that the
      transgene was expressed predominantly in SMCs of pulmonary and systemic vessels.
      Compared with wild-type mice, SM22-5-HTT(+) mice exhibited a 3- to 4-fold
      increase in lung 5-HTT mRNA and protein, together with increased lung 5-HT uptake
      activity, but no changes in platelet 5-HTT activity or blood 5-HT levels. At 8
      weeks of age, SM22-5-HTT(+) mice exhibited PH, with marked increases in right
      ventricular systolic pressure (RVSP), right ventricle/left ventricle+septum
      ratio, and muscularization of distal pulmonary vessels, but no changes in
      systemic arterial pressure. PH worsened with age. Except a marked decrease in Kv
      channels, no changes in the lung expression of mediators of pulmonary vascular
      remodeling were observed in SM22-5-HTT(+) mice. Compared with wild-type mice,
      SM22-5-HTT(+) mice showed depressed hypoxic pulmonary vasoconstriction
      contrasting with greater severity of hypoxia- or monocrotaline-induced PH. These
      results show that increased 5-HTT expression in PA-SMCs, to a level close to that
      found in human iPH, lead to PH in mice. They further support a central role for 5
      HTT in the pathogenesis of PH, making 5-HTT a potential therapeutic target.

PMID- 16614303
TI  - Hypoxia-mediated degradation of Na,K-ATPase via mitochondrial reactive oxygen
      species and the ubiquitin-conjugating system.
AB  - We set out to determine whether cellular hypoxia, via mitochondrial reactive
      oxygen species, promotes Na,K-ATPase degradation via the ubiquitin-conjugating
      system. Cells exposed to 1.5% O2 had a decrease in Na,K-ATPase activity and
      oxygen consumption. The total cell pool of alpha1 Na,K-ATPase protein decreased
      on exposure to 1.5% O2 for 30 hours, whereas the plasma membrane Na,K-ATPase was
      50% degraded after 2 hours of hypoxia, which was prevented by lysosome and
      proteasome inhibitors. When Chinese hamster ovary cells that exhibit a
      temperature-sensitive defect in E1 ubiquitin conjugation enzyme were incubated at
      40 degrees C and 1.5% O2, the degradation of the alpha1 Na,K-ATPase was
      prevented. Exogenous reactive oxygen species increased the plasma membrane Na,K
      ATPase degradation, whereas, in mitochondrial DNA deficient rho(0) cells and in
      cells transfected with small interfering RNA against Rieske iron sulfur protein,
      the hypoxia-mediated Na,K-ATPase degradation was prevented. The
      catalase/superoxide dismutase (SOD) mimetic (EUK-134) and glutathione peroxidase
      overexpression prevented the hypoxia-mediated Na,K-ATPase degradation and
      overexpression of SOD1, but not SOD2, partially inhibited the Na+ pump
      degradation. Accordingly, we provide evidence that during hypoxia, mitochondrial
      reactive oxygen species are necessary to degrade the plasma membrane Na,K-ATPase
      via the ubiquitin-conjugating system.

PMID- 16614304
TI  - Atherosclerotic plaque macrophage transcriptional regulators are expressed in
      blood and modulated by tristetraprolin.
AB  - Circulating monocytes and plaque macrophages mediate inflammation in the
      pathogenesis of atherosclerosis. We purified these cells from patients undergoing
      carotid endarterectomy for advanced atherosclerosis and examined their in vivo
      transcriptomes using the serial analysis of gene expression (SAGE) technique. We
      observed striking differences in transcriptional regulators as monocytes
      transformed into plaque macrophages in contrast to monocytes and lung macrophages
      from normal subjects. Consistent with its role in moderating inflammation,
      tristetraprolin (TTP, ZFP36) was among the most highly expressed macrophage
      transcriptional regulators. Interestingly, the mRNAs of a subset of the
      macrophage transcriptional regulators specifically interacted with TTP, revealing
      a network of genes that may be important in controlling macrophage inflammatory
      activity. Giving functional significance to this interaction, the knockdown of
      TTP increased both cognate macrophage gene mRNAs and inflammatory tumor necrosis
      factor protein release. In contrast, transient overexpression of TTP resulted in
      decreased levels of the same genes supporting its role in regulating macrophage
      gene expression. Together, our results indicate that the in vivo gene expression
      analyses of cells involved in pathogenesis can provide biological insights for
      functional studies with potential clinical implications.

PMID- 16614305
TI  - Activation of myocardial contraction by the N-terminal domains of myosin binding
      protein-C.
AB  - Myosin binding protein-C (MyBP-C) is a poorly understood component of the thick
      filament in striated muscle sarcomeres. Its C terminus binds tightly to myosin,
      whereas the N terminus contains binding sites for myosin S2 and possibly for the
      thin filament. To study the role of the N-terminal domains of cardiac MyBP-C
      (cMyBP-C), we added human N-terminal peptide fragments to human and rodent
      skinned ventricular myocytes. At concentrations >10 micromol/L, the N-terminal
      C0C2 peptide activated force production in the absence of calcium (pCa 9). Force
      at the optimal concentration (80 micromol/L) of C0C2 was approximately 60% of
      that in maximal Ca2+ (pCa 4.5), but the rate constant of tension redevelopment
      (ktr) matched or exceeded (by up to 80%) that produced by Ca2+ alone. Experiments
      using different N-terminal peptides suggested that this activating effect of C0C2
      resulted from binding by the pro/ala-rich C0-C1 linker region, rather than the
      terminal C0 domain. At a lower concentration (1 micromol/L), exogenous C0C2
      strongly sensitized cardiac myofibrils to Ca2+ at a sarcomere length (SL) of 1.9
      microm but had no significant effect at SL 2.3 microm. This differential effect
      caused the normal SL dependence of myofibrillar Ca2+ sensitivity to be reduced by
      80% (mouse myocytes) or abolished (human myocytes) in 1 micromol/L C0C2. These
      results suggest that cMyBP-C provides a regulatory pathway by which the thick
      filament can influence the activation of the thin filament, separately from its
      regulation by Ca2+. Furthermore, the N-terminal region of cMyBP-C can influence
      the SL-tension (Frank-Starling) relationship in cardiac muscle.

PMID- 16614307
TI  - Reducing ryanodine receptor open probability as a means to abolish spontaneous
      Ca2+ release and increase Ca2+ transient amplitude in adult ventricular myocytes.
AB  - The aim of this work was to investigate whether it is possible to remove
      arrhythmogenic Ca2+ release from the sarcoplasmic reticulum that occurs in
      calcium overload without compromising normal systolic release. Exposure of rat
      ventricular myocytes to isoproterenol (1 micromol/L) resulted in an increased
      amplitude of the systolic Ca2+ transient and the appearance of waves of diastolic
      Ca2+ release. Application of tetracaine (25 to 50 micromol/L) decreased the
      frequency or abolished the diastolic Ca2+ release. This was accompanied by an
      increase in the amplitude of the systolic Ca2+ transient. Cellular Ca2+ flux
      balance was investigated by integrating Ca2+ entry (on the L-type Ca2+ current)
      and efflux (on Na-Ca2+ exchange). Isoproterenol increased Ca2+ influx but failed
      to increase Ca2+ efflux during systole (because of the abbreviation of the
      duration of the Ca2+ transient). To match this increased influx the bulk of Ca2+
      efflux occurred via Na-Ca2+ exchange during a diastolic Ca2+ wave. Subsequent
      application of tetracaine increased systolic Ca2+ efflux and abolished the
      diastolic efflux. The increase of systolic efflux in tetracaine resulted from
      both increased amplitude and duration of the systolic Ca2+ transient. In the
      presence of isoproterenol, those Ca2+ transients preceded by diastolic release
      were smaller than those where no diastolic release had occurred. When tetracaine
      was added, the amplitude of the Ca2+ transient was similar to those in
      isoproterenol with no diastolic release and larger than those preceded by
      diastolic release. We conclude that tetracaine increases the amplitude of the
      systolic Ca2+ transient by removing the inhibitory effect of diastolic Ca2+
      release.

PMID- 16614306
TI  - Differential calcineurin/NFATc3 activity contributes to the Ito transmural
      gradient in the mouse heart.
AB  - Kv4 channels are differentially expressed across the mouse left ventricular free
      wall. Accordingly, the transient outward K+ current (Ito), which is produced by
      Kv4 channels, is greater in left ventricular epicardial (EPI) than in endocardial
      (ENDO) cells. However, the mechanisms underlying heterogeneous Kv4 expression in
      the heart are unclear. Here, we tested the hypothesis that differential [Ca2+]i
      and calcineurin/NFATc3 signaling in EPI and ENDO cells contributes to the
      gradient of Ito function in the mouse left ventricle. In support of this
      hypothesis, we found that [Ca2+]i, calcineurin, and NFAT activity were greater in
      ENDO than in EPI myocytes. However, the amplitude of Ito was the same in ENDO and
      EPI cells when [Ca2+]i, calcineurin, and NFAT activity were equalized. Consistent
      with this, we observed complete loss of Ito and Kv4 heterogeneity in NFATc3-null
      mice. Interestingly, Kv4.3, Kv4.2, and KChIP2 genes had different apparent
      thresholds for NFATc3-dependent suppression and were ordered as Kv4.3
      approximately KChIP2>Kv4.2. Based on these data, we conclude that calcineurin and
      NFATc3 constitute a Ca(2+)-driven signaling module that contributes to the
      nonuniform distribution of Kv4 expression, and hence Ito function, in the mouse
      left ventricle.

PMID- 16614308
TI  - Pitting phosphate transport inhibitors against vascular calcification.

PMID- 16614309
TI  - Serotonin-induced inhibition of KV current: a supporting role in pulmonary
      vasoconstriction?

PMID- 16614310
TI  - Mechanical and chemical regulation of endothelial cell polarity.

PMID- 16614311
TI  - Endothelial dysfunction and hypertension in rats transduced with CYP4A2
      adenovirus.

PMID- 16614312
TI  - Excitation-transcription coupling in arterial smooth muscle.
AB  - The primary function of the vascular smooth muscle cell (SMC) is contraction for
      which SMCs express a selective repertoire of genes (eg, SM alpha-actin, SM myosin
      heavy chain [SMMHC], myocardin) that ultimately define the SMC from other muscle
      cell types. Moreover, the SMC exhibits extensive phenotypic diversity and
      plasticity, which play an important role during normal development, repair of
      vascular injury, and in vascular disease states. Diverse signals modulate ion
      channel activity in the sarcolemma of SMCs, resulting in altered intracellular
      calcium (Ca) signaling, activation of multiple intracellular signaling cascades,
      and SMC contraction or relaxation, a process known as "excitation-contraction
      coupling" (EC-coupling). Over the past 5 years, exciting new studies have shown
      that the same signals that regulate EC-coupling in SMCs are also capable of
      regulating SMC-selective gene expression programs, a new paradigm coined
      "excitation-transcription coupling" (ET-coupling). This article reviews recent
      progress in our understanding of the mechanisms by which ET-coupling selectively
      coordinates the expression of distinct gene subsets in SMCs by disparate
      transcription factors, including CREB, NFAT, and myocardin, via selective
      kinases. For example, L-type voltage-gated Ca2+ channels modulate SMC
      differentiation marker gene expression, eg, SM alpha-actin and SMMHC, via Rho
      kinase and myocardin and also regulate c-fos gene expression independently via
      CaMK. In addition, we discuss the potential role of IK channels and TRPC in ET
      coupling as potential mediators of SMC phenotypic modulation, ie, negatively
      regulate SMC differentiation marker genes, in vascular disease.

PMID- 16614313
TI  - Emerging imaging techniques.
AB  - This article reviews recent developments in selected imaging technologies focused
      on the cardiovascular system. The techniques covered are: ultrasound
      biomicroscopy (UBM), microSPECT, microPET, near infrared imaging, and quantum
      dots. For each technique, the basic physical principles are explained and recent
      example applications demonstrated.

PMID- 16614314
TI  - Signaling by the angiotensin-converting enzyme.
AB  - Inhibition of the angiotensin-converting enzyme (ACE) protects against the
      progression of several cardiovascular diseases. Because of its dual role in
      regulating angiotensin II and bradykinin levels, the positive clinical effects of
      ACE inhibitors were thought to be the consequence of concomitant reductions in
      the production of angiotensin II and the degradation of bradykinin. Recent
      evidence suggests that some of the beneficial effects of ACE inhibitors on
      cardiovascular function and homeostasis can be attributed to novel mechanisms.
      These include the accumulation of the ACE substrate N-acetyl-seryl-aspartyl-lysyl
      proline, which blocks collagen deposition in the injured heart, as well as the
      activation of an ACE signaling cascade that involves the activation of the kinase
      CK2 and the c-Jun N-terminal kinase in endothelial cells and leads to changes in
      gene expression. Moreover, at least one other ACE homologue (ACE2) is proposed to
      counteract the detrimental effects associated with the activation of the
      classical renin-angiotensin system. These data reveal hitherto unexpected levels
      of internal regulation of the renin-angiotensin system.

PMID- 16614315
TI  - In vivo low-density lipoprotein exposure induces intercellular adhesion molecule
      1 and vascular cell adhesion molecule-1 correlated with activator protein-1
      expression.
AB  - OBJECTIVE: We tested the hypothesis that direct native low-density lipoprotein
      (LDL) injection into LDL receptor-deficient (LDLR(-/-)) mice would induce the
      adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1) in their aortic endothelial cells, and that
      transcriptional regulation of this pathway involved activator protein-1 (AP-1)
      but not nuclear factor kappaB (NF-kappaB). METHODS AND RESULTS: Using tail vein
      injection of LDL into LDLR(-/-) mice, we were able to maintain atherogenic LDL
      blood levels, which induced ICAM-1 and VCAM-1 expression in their aortic
      endothelial cells after 24 hours. We were able to visualize and quantify this
      expression using immunohistochemistry and confocal microscopy. Under conditions
      in which ICAM-1 and VCAM-1 were expressed, the regulatory AP-1 proteins c-Fos and
      c-Jun were also highly expressed in the endothelial cell cytoplasm and observed
      within the cell nucleus. The NF-kappaB protein P65, although expressed in the
      endothelial cell cytoplasm after LDL injection, was not observed within the cell
      nucleus. CONCLUSIONS: Elevated LDL blood levels, maintained in vivo, increased
      the expression of the adhesion molecules ICAM-1 and VCAM-1 in aortic endothelial
      cells. This effect appeared to correlate with AP-1 but not NF-kappaB.

PMID- 16614317
TI  - Hyperinsulinemia is associated with increased production rate of intestinal
      apolipoprotein B-48-containing lipoproteins in humans.
AB  - OBJECTIVE: Whereas postprandial hyperlipidemia is a well-described feature of
      insulin-resistant states and type 2 diabetes, no previous studies have examined
      intestinal lipoprotein production rates (PRs) in relation to hyperinsulinemia or
      insulin resistance in humans. METHODS AND RESULTS: Apolipoprotein B-48 (apoB-48)
      containing lipoprotein metabolism was examined in the steady-state fed condition
      with a 15-hour primed constant infusion of [D3]-l-leucine in 14 nondiabetic men
      with a broad range of body mass index (BMI) and insulin sensitivity. To examine
      the relationship between indices of insulin resistance and intestinal lipoprotein
      PR data were analyzed in 2 ways: by correlation and by comparing apoB-48 PRs in
      those whose fasting plasma insulin concentrations were above or below the median
      for the 14 subjects studied (60 pmol/L). ApoB-48 PR was significantly higher in
      hyperinsulinemic, insulin-resistant subjects (1.73+/-0.39 versus 0.88+/-0.13
      mg/kg per day; P<0.05) and correlated with fasting plasma insulin concentrations
      (r=0.558; P=0.038), despite great heterogeneity in apoB-48 kinetic parameters,
      particularly among the obese subjects. There was no significant difference in
      clearance of apoB-48 between the 2 groups, nor was there a significant
      correlation between apoB-48 fractional clearance rate and fasting insulin or
      homeostasis model assessment-insulin resistance. CONCLUSIONS: These are the first
      human data to conclusively demonstrate that intestinal apoB-48-containing
      triglyceride-rich lipoprotein PR is increased in hyperinsulinemic, insulin
      resistant humans. Intestinal lipoprotein particle overproduction is a newly
      described feature of insulin resistance in humans.

PMID- 16614316
TI  - Pleiotrophin induces transdifferentiation of monocytes into functional
      endothelial cells.
AB  - OBJECTIVE: Pleiotrophin (PTN) is a cytokine that is expressed by
      monocytes/macrophages in ischemic tissues and that promotes neovascularization,
      presumably by stimulating proliferation of local endothelial cells. However, the
      effect of PTN on monocytes/macrophages remains unknown. We investigated the role
      of PTN in regulating the phenotype of monocytes/macrophages. METHODS AND RESULTS:
      RT-PCR, real-time PCR, and fluorescence-activated cell sorter analysis revealed
      that the expression of PTN by monocytic cells led to a downregulation of CD68, c
      fms, and CD14 monocytic cell markers and an upregulation of FLK-1, Tie-2,
      vascular endothelial-cadherin, platelet endothelial cell adhesion molecule-1,
      endothelial NO synthase, von Willebrand factor, CD34, GATA-2, and GATA-3
      endothelial cell markers. Fibrin gel assays showed that the treatment of mouse
      and human monocytic cells with PTN led to the formation of tube-like structures.
      In vivo studies showed that PTN-expressing monocytic cells incorporated into the
      blood vessels of the quail chorioallantoic membrane. The intracardial injection
      of PTN-expressing monocytic cells into chicken embryos showed that cells
      integrated only into the developing vasculature. Finally, the injection of PTN
      expressing monocytes into a murine ischemic hindlimb model significantly improved
      perfusion of the ischemic tissue. CONCLUSIONS: PTN expression by
      monocytes/macrophages led to a downregulation of their monocytic cell markers and
      an upregulation of endothelial cell characteristics, thus inducing the
      transdifferentiation of monocytes into functional endothelial cells.

PMID- 16614318
TI  - Young adults with family history of coronary heart disease have increased
      arterial vulnerability to metabolic risk factors: the Cardiovascular Risk in
      Young Finns Study.
AB  - OBJECTIVE: Subjects with family history for coronary heart disease (CHD) may be
      more susceptible to the adverse effects of risk factors than subjects without
      family history. We investigated the occurrence of subclinical atherosclerosis in
      young adults with family history of CHD and tested the hypothesis that their
      arteries are more vulnerable to the proatherogenic effects of metabolic risk
      factors. METHODS AND RESULTS: Carotid artery intima-media thickness (IMT),
      carotid artery compliance (CAC), and brachial artery flow-mediated dilation (FMD)
      were measured in the 21-year follow-up of the Cardiovascular Risk in Young Finns
      Study in 2265 white adults 24 to 39 years of age. Subjects with positive family
      history of CHD had greater IMT compared with those with negative history (mean+/
      SEM; 0.600+/-0.006 versus 0.578+/-0.002 mm; P=0.003, respectively). No
      differences were observed in CAC or FMD (both P>0.2). The difference in IMT
      remained similar after adjustment with current risk factors (P=0.008) or
      childhood risk factors measured 21 years earlier (P=0.002). The number of
      metabolic risk factors (components of the NCEP metabolic syndrome) correlated
      more strongly with IMT in subjects with family history of CHD than those without
      (P=0.007 for interaction). CONCLUSIONS: Young healthy adults with family history
      of CHD have increased carotid IMT. This is partly explained by their increased
      vulnerability to metabolic risk factors.

PMID- 16614319
TI  - Common genetic variation in five thrombosis genes and relations to plasma
      hemostatic protein level and cardiovascular disease risk.
AB  - OBJECTIVE: We undertook a linkage disequilibrium (LD)-based genetic approach to
      investigate the hypothesis that common sequence variants in 5 thrombosis genes
      influence plasma hemostatic protein levels or risk of cardiovascular disease
      (CVD). METHODS AND RESULTS: In a reference panel, we characterized LD structure
      at the fibrinogen gene cluster (fibrinogen-beta[FGB], FGA, and FGG), factor VII
      (F7), and tissue plasminogen activator (PLAT) loci. Forty-one tag single
      nucleotide polymorphisms (SNPs) were genotyped in 1811 unrelated Framingham Heart
      Study participants. There were significant associations of 9 FGB SNPs with
      fibrinogen level (minimum P=0.002) and of 7 F7 SNPs and factor VII level (minimum
      P<0.0001). SNPs at the PLAT locus were not associated with PLAT level. In
      stepwise analysis, a single FGB variant explained 1% of the residual variance in
      fibrinogen level, and 2 F7 SNPs together explained 10% of the residual variance
      in factor VII level. Two PLAT haplotypes were associated with CVD (multivariable
      adjusted global P=0.0004). CONCLUSIONS: A comprehensive survey of common sequence
      variation demonstrates that cis-regulatory SNPs explain a modest proportion of
      the residual variance in circulating fibrinogen and factor VII level and PLAT
      haplotypes increase the risk of CVD. Additional studies are warranted to confirm
      the association of PLAT sequence variation and risk of CVD.

PMID- 16614320
TI  - Unruptured cerebral arteriovenous malformations: to treat or not to treat.

PMID- 16614321
TI  - Clinical outcome after first and recurrent hemorrhage in patients with untreated
      brain arteriovenous malformation.
AB  - BACKGROUND AND PURPOSE: The morbidity from spontaneous hemorrhage of untreated
      brain arteriovenous malformations (AVM) is not well described. METHODS: The 241
      consecutive AVM patients (mean age 37+/-16 years, 52% women) from the prospective
      Columbia AVM Databank initially presenting with hemorrhage were evaluated using
      the Rankin Scale (RS) and the National Institute of Health Stroke Scale (NIHSS).
      From the 241 AVM patients, 29 (12%) had subsequent intracranial hemorrhage during
      follow-up. For further comparisons, 84 non-AVM patients with intracerebral
      hemorrhage from the Northern Manhattan Study (NOMAS) served as a control group.
      RESULTS: In 241 AVM patients presenting with hemorrhage the median RS was 2 and
      the median NIHSS was 1 (49% RS 0 to 1, 61% NIHSS <2). The median time between
      hemorrhage and clinical evaluation was 11 days (mean 219 days). Recurrent AVM
      hemorrhage during follow-up resulted in no significant increase in morbidity
      (median RS 2, P=0.004; median NIHSS 3, P=0.322; time between hemorrhage and study
      evaluation: median 55 days, mean 657 days). Among AVM-hemorrhage subtypes,
      parenchymatous AVM hemorrhage was associated with higher stroke morbidity (odds
      ratio, 2.9; 95% CI, 1.5 to 5.8 for NIHSS > or =2) than nonparenchymatous
      hemorrhages. Parenchymatous AVM hemorrhage had a significantly better outcome
      (median NIHSS 1) than non-AVM related hemorrhage (median NIHSS 12; P<0.0001).
      CONCLUSIONS: Hemorrhage, either at initial presentation or during follow-up of
      untreated AVM patients appears to carry a lower morbidity than intracranial
      hemorrhage from other causes. These findings support a careful weighing of risks
      from interventional treatment and natural history.

PMID- 16614322
TI  - Vasal reconstruction above the internal inguinal ring: what are the options?

PMID- 16614323
TI  - Is TESA Passe?

PMID- 16614324
TI  - Autism and diet.

PMID- 16614325
TI  - Antonovsky's sense of coherence scale and the relation with health: a systematic
      review.
AB  - STUDY OBJECTIVE: The aim of this paper is to synthesise empirical findings on the
      salutogenic concept sense of coherence (SOC) and examine its capacity to explain
      health and its dimensions. DESIGN: The study is descriptive and analytical with a
      systematic integration of the contemporary knowledge base on the salutogenic
      research published 1992-2003. The review includes 458 scientific publications and
      13 doctoral theses. SETTING: Worldwide, based on postgraduate scientific
      publications in eight authorised databases, doctoral theses, and available books.
      MAIN RESULTS: SOC is strongly related to perceived health, especially mental
      health. The stronger the SOC the better the perceived health in general, at least
      for those with an initial high SOC. This relation is manifested in study
      populations regardless of age, sex, ethnicity, nationality, and study design. SOC
      seems to have a main, moderating or mediating role in the explanation of health.
      Furthermore, the SOC seems to be able to predict health. SOC is an important
      contributor for the development and maintenance of people's health but does not
      alone explain the overall health. CONCLUSION: SOC seems to be a health promoting
      resource, which strengthens resilience and develops a positive subjective state
      of health. Salutogenesis is a valuable approach for health promotion and would be
      worth to implement in practice much more than to date.

PMID- 16614326
TI  - Randomised by (your) god: robust inference from an observational study design.

PMID- 16614327
TI  - Neighbourhoods and health: a GIS approach to measuring community resource
      accessibility.
AB  - OBJECTIVE: Recent studies suggest an association between the contextual
      attributes of neighbourhoods and the health status of residents. However, there
      has been a scarcity of studies that have directly measured the material
      characteristics of neighbourhoods theorised to have an impact on health and
      health inequalities. This paper describes the development of an innovative
      methodology to measure geographical access to a range of community resources that
      have been empirically linked to health. Geographical information systems (GIS)
      were applied to develop precise measures of community resource accessibility for
      small areas at a national scale. DESIGN: Locational access to shopping,
      education, recreation, and health facilities was established for all 38,350
      census meshblocks across New Zealand. Using GIS, distance measures were
      calculated from the population weighted centroid of each meshblock to 16 specific
      types of facilities theorised as potentially health related. From these data,
      indices of community resource accessibility for all New Zealand neighbourhoods
      were constructed. RESULTS: Clear regional variations in geographical
      accessibility to community resources exist across the country, particularly
      between urban and rural areas of New Zealand. For example, the average travel
      time to the nearest food shop ranged from less than one minute to more than 244
      minutes. Noticeable differences were also apparent between neighbourhoods within
      urban areas. CONCLUSIONS: Recent advances in GIS and computing capacity have made
      it feasible to directly measure access to health related community resources at
      the neighbourhood level. The construction of access indices for specific
      community resources will enable health researchers to examine with greater
      precision, variations in the material characteristics of neighbourhoods and the
      pathways through which neighbourhoods impact on specific health outcomes.

PMID- 16614328
TI  - Sick individuals and sick populations: 20 years later.
AB  - Twenty years after Geoffrey Rose published his classic paper, the central
      messages remain highly relevant to modern public health policy and practice. The
      individual and population approaches are fundamentally different but both are
      needed. Recent examples of powerful population approaches prove Rose's point that
      norms can change benefiting the most deprived. Individual approaches have also
      succeeded but their protection of the most deprived communities is limited.
      Consumerism in health and over-reliance on individual approaches risk widening
      health inequalities.

PMID- 16614329
TI  - Influenza pandemic preparedness in France: modelling the impact of interventions.
AB  - BACKGROUND: Influenza pandemics result in excess mortality and social disruption.
      To assist health authorities update the French pandemic plan, the authors
      estimated the number of health events (cases, hospitalisations, and deaths) in a
      pandemic and compared interventions in terms of impact and efficiency. METHOD: A
      Monte Carlo simulation model, incorporating probability distributions of key
      variables, provided estimates of health events (HE) by age and risk group. Input
      variables were set after literature and expert consultation. The impact of
      targeted influenza vaccination and antiviral prophylaxis/treatment (oseltamivir)
      in high risk groups (elderly, chronic diseases), priority (essential
      professionals), and total populations was compared. Outcome measures were HE
      avoided, number of doses needed, and direct cost per HE avoided. RESULTS: Without
      intervention, an influenza pandemic could result in 14.9 million cases, 0.12
      million deaths, and 0.6 million hospitalisations in France. Twenty four per cent
      of deaths and 40% of hospitalisations would be among high risk groups. With a 25%
      attack rate, 2000-86,000 deaths could be avoided, depending on population
      targeted and intervention. If available initially, vaccination of the total
      population is preferred. If not, for priority populations, seasonal prophylaxis
      seems the best strategy. For high risk groups, antiviral treatment, although less
      effective, seems more feasible and cost effective than prophylaxis (respectively
      29% deaths avoided; 1800 doses/death avoided and 56% deaths avoided; 18,500
      doses/death avoided) and should be chosen, especially if limited drug
      availability. CONCLUSION: The results suggest a strong role for antivirals in an
      influenza pandemic. While this model can compare the impact of different
      intervention strategies, there remains uncertainty surrounding key variables.

PMID- 16614330
TI  - Quitting smoking and experience of smoking cessation interventions among UK
      Bangladeshi and Pakistani adults: the views of community members and health
      professionals.
AB  - OBJECTIVE: To explore attitudes to quitting smoking and experience of smoking
      cessation among Bangladeshi and Pakistani ethnic minority communities. DESIGN:
      Qualitative study using community participatory methods, purposeful sampling,
      interviews and focus groups, and a grounded approach to data generation and
      analysis. SETTING: Newcastle upon Tyne, UK, 2000-2002. PARTICIPANTS: 53 men and
      20 women aged 18-80 years, including smokers, former smokers, and smokers'
      relatives, from the Bangladeshi and Pakistani communities; and eight health
      professionals working with these communities. RESULTS: Motivation to quit was
      high but most attempts had failed. "Willpower" was the most common approach to
      quitting. For some, the holy month of Ramadan was used as an incentive, however
      few had been successful in quitting. Perceived barriers to success included being
      tempted by others, everyday stresses, and withdrawal symptoms. Few participants
      had sought advice from health services, or received cessation aids, such as
      nicotine replacement therapy (NRT) or buproprion. Family doctors were not viewed
      as accessible sources of advice on quitting. Health professionals and community
      members identified common barriers to accessing effective smoking cessation,
      including: language, religion and culture; negative attitudes to services; and
      lack of time and resources for professionals to develop necessary skills.
      CONCLUSIONS: High levels of motivation do not seem to be matched by effective
      interventions or successful attempts to quit smoking among Bangladeshi and
      Pakistani adults in the UK. There is a need to adapt and test effective smoking
      cessation interventions to make them culturally acceptable to ethnic minority
      communities. UK tobacco control policies need to give special attention to the
      needs of ethnic minority groups.

PMID- 16614331
TI  - Actual and preferred place of death of cancer patients. Results from the Italian
      survey of the dying of cancer (ISDOC).
AB  - OBJECTIVE: To describe actual and preferred place of death of Italian cancer
      patients and to analyse the preferences met regarding the place of death. DESIGN:
      Mortality follow back survey of 2000 cancer deaths, identified with a two stage
      probability sample representative of the whole country. Information on patients'
      experience was gathered from the non-professional caregiver with an interview. A
      section of the interview covered information on the actual and preferred place of
      death of the patients. SETTING: 30 Italian local health districts randomly
      selected after stratification in four geographical areas. PARTICIPANTS: 1900 of
      2000 (95.0%) caregivers of cancer deaths identified. MAIN OUTCOME MEASURES:
      Prevalence of actual and preferred places of death. RESULTS: Valid interviews
      were obtained for 66.9% (n = 1271) of the caregivers. Place of death was home for
      57.9% of Italian cancer patients, hospital for 34.6%, hospice for 0.7%, nursing
      home for 6.5%, and ambulance for 0.4%. Wide and significant differences within
      Italy were seen (home deaths ranged between 94.0% in the south and 28.2% in the
      north east). Home was the preferred place of death for 93.5% of patients that
      expressed a preference, with minimal differences within the country (between
      89.5% and 99.0%). Overall 67.1% of the sample died in the place where they
      preferred to die. CONCLUSIONS: Policymakers should encourage health services to
      focus on ways of meeting individual preferences on place of death. As home was
      the preferred place of death for most cancer patients, effective programmes to
      enable the patients to remain at home should be implemented.

PMID- 16614332
TI  - Temperature and summer mortality: geographical and temporal variations in four
      Italian cities.
AB  - STUDY OBJECTIVE: To investigate geographical and temporal variations in the
      temperature-mortality relation. DESIGN: The relation between mortality and
      maximum apparent temperature (Tappmax) in 2003, 2004, and a previous reference
      period was explored by using segmented regression and generalised additive
      models. SETTING: Four Italian cities (Bologna, Milano, Roma, and Torino),
      included in a national network of prevention programmes and heat health watch
      warning systems (HHWWS) were considered. PARTICIPANTS: Daily mortality counts of
      the resident population dying in each city during summer (June to September).
      MAIN RESULTS: The impact of Tappmax on mortality differed between cities and
      varied in the three periods analysed. The geographical heterogeneity of the J
      shaped relation was seen in the reference period with Tappmax thresholds ranging
      from 28 degrees C in Torino to 32 degrees C in Milano and Roma. In all cities,
      the percentage variation in mortality was greatest in 2003. In Torino and Roma a
      significant increase was seen also at lower Tappmax values that are usually not
      associated to an increase in mortality (26-28 degrees C). In summer 2004 the
      exposure levels were similar to the reference period; only in Torino the effect
      of Tappmax on mortality remained relevant even if reduced compared with 2003,
      while in Bologna no statistically significant effect was seen for any temperature
      range. CONCLUSIONS: The observed heterogeneous reduction in the impact of
      temperature on mortality from 2003 to 2004 may be partly explained by the lower
      levels of exposure. Changes in the ability of individuals and communities to
      adjust to high temperatures as a consequence of the implementation of public
      health interventions, based on HHWWS, characterised by a diverse effectiveness,
      may also have played an important part.

PMID- 16614333
TI  - Risk of fatal and non-fatal occupational injury in foreign workers in Spain.
AB  - STUDY OBJECTIVE: In the past decade, Spain has experienced dramatic growth of its
      immigrant population. Available information on the occupational conditions of
      foreign workers is scarce. This study aims to add to this information by
      describing occupational injuries in foreign workers in Spain. DESIGN, SETTING,
      PARTICIPANTS: Data were analysed from the 2003 Ministry of Labour and Social
      Issues registry of non-fatal and fatal occupational injury in insured workers.
      The population at risk was estimated from the Social Security Affiliation
      Registry as of 31 December 2003. Comparing Spanish with foreign workers and also
      considering age and sex, incidence rates and relative risks, and their confidence
      intervals at 95%, were calculated within each population group. MAIN RESULTS: In
      women and in men, and in every age group, foreign workers had an increased risk
      of non-fatal and fatal occupational injury compared with Spanish workers. The
      differences were especially notable in foreign women workers and in older
      workers. CONCLUSIONS: Many factors probably combine to cause the differences
      found in this study. Better data collection on the situation of foreign workers
      is needed to understand these facts and apply appropriate public health
      solutions.

PMID- 16614334
TI  - Spatial clustering of mental disorders and associated characteristics of the
      neighbourhood context in Malmo, Sweden, in 2001.
AB  - STUDY OBJECTIVE: Previous research provides preliminary evidence of spatial
      variations of mental disorders and associations between neighbourhood social
      context and mental health. This study expands past literature by (1) using
      spatial techniques, rather than multilevel models, to compare the spatial
      distributions of two groups of mental disorders (that is, disorders due to
      psychoactive substance use, and neurotic, stress related, and somatoform
      disorders); and (2) investigating the independent impact of contextual
      deprivation and neighbourhood social disorganisation on mental health, while
      assessing both the magnitude and the spatial scale of these effects. DESIGN:
      Using different spatial techniques, the study investigated mental disorders due
      to psychoactive substance use, and neurotic disorders. PARTICIPANTS: All 89,285
      persons aged 40-69 years residing in Malmo, Sweden, in 2001, geolocated to their
      place of residence. MAIN RESULTS: The spatial scan statistic identified a large
      cluster of increased prevalence in a similar location for the two mental
      disorders in the northern part of Malmo. However, hierarchical geostatistical
      models showed that the two groups of disorders exhibited a different spatial
      distribution, in terms of both magnitude and spatial scale. Mental disorders due
      to substance consumption showed larger neighbourhood variations, and varied in
      space on a larger scale, than neurotic disorders. After adjustment for individual
      factors, the risk of substance related disorders increased with neighbourhood
      deprivation and neighbourhood social disorganisation. The risk of neurotic
      disorders only increased with contextual deprivation. Measuring contextual
      factors across continuous space, it was found that these associations operated on
      a local scale. CONCLUSIONS: Taking space into account in the analyses permitted
      deeper insight into the contextual determinants of mental disorders.

PMID- 16614335
TI  - Explaining the social gradient in coronary heart disease: comparing relative and
      absolute risk approaches.
AB  - STUDY OBJECTIVES: There are contradictory perspectives on the importance of
      conventional coronary heart disease (CHD) risk factors in explaining population
      levels and social gradients in CHD. This study examined the contribution of
      conventional CHD risk factors (smoking, hypertension, dyslipidaemia, and
      diabetes) to explaining population levels and to absolute and relative social
      inequalities in CHD. This was investigated in an entire population and by
      creating a low risk sub-population with no smoking, dyslipidaemia, diabetes, and
      hypertension to simulate what would happen to relative and social inequalities in
      CHD if conventional risk factors were removed. DESIGN, SETTING, AND PARTICIPANTS:
      Population based study of 2682 eastern Finnish men aged 42, 48, 54, 60 at
      baseline with 10.5 years average follow up of fatal (ICD9 codes 410-414) and non
      fatal (MONICA criteria) CHD events. MAIN RESULTS: In the whole population, 94.6%
      of events occurred among men exposed to at least one conventional risk factor,
      with a PAR of 68%. Adjustment for conventional risk factors reduced relative
      social inequality by 24%. However, in a low risk population free from
      conventional risk factors, absolute social inequality reduced by 72%.
      CONCLUSIONS: Conventional risk factors explain the majority of absolute social
      inequality in CHD because conventional risk factors explain the vast majority of
      CHD cases in the population. However, the role of conventional risk factors in
      explaining relative social inequality was modest. This apparent paradox may arise
      in populations where inequalities in conventional risk factors between social
      groups are low, relative to the high levels of conventional risk factors within
      every social group. If the concern is to reduce the overall population health
      burden of CHD and the disproportionate population health burden associated with
      the social inequalities in CHD, then reducing conventional risk factors will do
      the job.

PMID- 16614336
TI  - Are there socioeconomic differences in myocardial infarction event rates and
      fatality among patients with angina pectoris?
AB  - BACKGROUND: Systematic socioeconomic differences in mortality have been reported
      among myocardial infarction (MI) patients in many countries, including Finland.
      The findings have been similar irrespective of country, study period, age group,
      or length of follow up, but few studies have examined the disparities among other
      groups of coronary patients. This study examined whether similar socioeconomic
      differences in outcomes exist among patients with angina pectoris (AP). METHODS:
      The data were based on individual register linkages among a population based 40
      79 year-old cohort of 61,350 patients with incident AP or MI during 1995-1998 in
      Finland. Two year coronary heart disease mortality and one year MI incidence and
      its 28 day case fatality was studied among AP patients using Cox's and logistic
      regression analysis, and the results compared with those of the MI patient group.
      RESULTS: A clear socioeconomic pattern was found in two year coronary heart
      disease (CHD) mortality: the lower the socioeconomic group the higher the
      mortality risk. The socioeconomic patterning of mortality was similar to that
      found among MI patients. Controlling for comorbidity or disease severity did not
      change the results. Among AP patients a similar pattern was also found in MI
      incidence during the follow up, but no systematic socioeconomic differences were
      detected in its 28 day case fatality. CONCLUSIONS: Socioeconomic differences in
      CHD outcomes also exist among angina patients. These results suggest that
      targeted measures of secondary prevention are needed among CHD patients with
      lower socioeconomic status to reduce socioeconomic disparities in fatal and non
      fatal coronary events.

PMID- 16614337
TI  - Successful aging: measuring the years lived with functional loss.
AB  - Current research of risk factors potentially associated with successful aging
      faces the difficulty of taking into consideration two distinct outcome measures:
      survival and functioning. Previous studies either used successful aging measures
      restricted to survivors or presented more than one outcome measure to handle the
      dual outcome. This article illustrates the utility of health expectancy measures,
      based on life tables, to integrate the effects of survival and functioning across
      all ages. It is shown that three hypothetical successful aging strategies,
      considered equally successful according to the traditional measures restricted to
      survivors, are associated with vastly different changes in the years lived with
      and without disability. Furthermore, the intervention considered most successful
      when considering multiple successful aging measures, was associated with the
      largest increase in the time lived with disability. It is recommended that
      research on successful aging should be based on summary measures of population
      health that reflect both survival and functioning throughout life. These will
      provide more relevant information than is currently available for individuals and
      societies to evaluate and choose between successful aging strategies.

PMID- 16614338
TI  - Introduction: aging among Latin American and Caribbean populations.

PMID- 16614339
TI  - Survey data for the study of aging in Latin America and the Caribbean: selected
      studies.
AB  - The article summarizes three of the data collection studies that can assist
      researchers in examining population aging processes in the Latin America and
      Caribbean region with an emphasis on cross-national comparisons, including the
      population of Mexican immigrants in the United States. These are the Survey on
      Health and Wellbeing of Elders conducted in seven urban centers of the region,
      the national Mexican Health and Aging Study, and the Hispanic Established
      Populations for Epidemiologic Studies of the Elderly in the United States. The
      article describes the studies and marks them as informative, comprehensive, and
      still underanalyzed in particular for the purpose of cross-national analyses of
      aging among Latin American and Caribbean populations.

PMID- 16614340
TI  - The tide to come: elderly health in Latin America and the Caribbean.
AB  - This article introduces a conjecture and reviews partial evidence about
      peculiarities in the aging of populations in Latin America and the Caribbean
      (LAC) that may impact future elderly health status. Using Survey on Health and
      Well-Being of Elders data (SABE; n = 10,902), the authors estimated effects of
      early childhood conditions on adult diabetes and heart disease. Using Waaler-type
      surfaces, the authors obtained expected mortality risks for SABE and also U.S.
      elderly (Health and Retirement System, n = 12,527). Expected mortality risks
      using Waaler-type surfaces among elderly in LAC reflected excesses supporting our
      conjecture. There was partial evidence of a relation between various indicators
      of early childhood nutritional status (knee height, waist-to-hip ratio) and
      diabetes and even stronger evidence of a relation between rheumatic fever and
      adult heart disease. There is some evidence, albeit weak, to suggest that the
      conjecture regarding elderly health status' connection to early conditions has
      some merit.

PMID- 16614341
TI  - Prevalence of self-reported arthritis among elders from Latin America and the
      Caribbean and among Mexican Americans from the southwestern United States.
AB  - This study examines the prevalence of self-reported arthritis and arthritis
      symptoms and their relationship to functional limitations in elders from Latin
      America and the Caribbean and in Mexican Americans from the southwestern United
      States. This study includes 8,122 elderly aged 60 and older from seven Latin
      America and Caribbean countries and 2,580 noninstitutionalized Mexican Americans
      aged 65 or older residing in the southwestern United States. The estimated
      prevalence of self-reported arthritis ranged from 23.8% in Mexico City to 55.6%
      in Havana. The prevalence of self-reported pain among arthritic subjects across
      all countries ranged from 30.7% in older Mexican Americans to 83.7% in Santiago.
      Arthritis was independently associated with any Activities of Daily Living and
      any Instrumental Activities of Daily Living limitation across the eight countries
      after controlling for relevant factors. Self-reported arthritis and arthritis
      symptoms are highly prevalent among elders from Latin America and the Caribbean
      and older Mexican Americans and is a significant cause of disability in all
      studied populations.

PMID- 16614342
TI  - The prevalence of diagnosed diabetes among the elderly of seven cities in Latin
      America and the Caribbean: The Health Wellbeing and Aging (SABE) Project.
AB  - OBJECTIVE: To examine the relation of diagnosed diabetes mellitus (DM) to the
      level of education and body mass index (BMI) among the elderly of seven cities
      using data from SABE. METHODS: The SABE survey was based on a probabilistic
      sample of the elderly population. RESULTS: Results: The prevalence of diagnosed
      diabetes among the elderly was 15.7% (95% CI 14.7-16.8), with the highest
      prevalence reported in Bridgetown and the lowest in Buenos Aires. DISCUSSION:
      There was a high prevalence of diagnosed DM among the elderly of the seven
      cities. The prevalence of diagnosed DM was strongly associated with BMI and low
      education. The inclusion of these factors in policies and programs aiming to
      reduce the prevalence of diabetes among the elderly is recommended.

PMID- 16614343
TI  - Prevalence and risk factors associated with obesity in the elderly in Barbados.
AB  - This article's objective is to examine the epidemiology of obesity in the urban
      elderly population of Barbados. A random sample of adults >/= 60 years underwent
      comprehensive interviews and measurement of their weight, height, and waist
      circumference (WC). Outcomes of interest were obesity (body mass index [BMI] > 30
      kg/m2), high-risk WC (men >/= 102 cm; women >/= 88 cm), and high risk of disease
      comorbidity (from BMI and WC criteria). Total, 1,508 persons participated (80%
      response). Women had higher rates of obesity (31% vs. 11.9%), high-risk WC (61.9%
      vs. 13.9%), and disease co-morbidity risk (51.1% vs. 17.5%) compared to men.
      Multivariate regression confirmed female gender as an independent predictor of
      outcomes (p < 0.001). Other predictors were less consistent: self-reported
      fair/poor health status and eating two (vs. three) meals daily were associated
      with obesity, whereas semiprofessional occupation and unmarried status predicted
      high-risk WC. Obesity is highly prevalent among elderly Barbadians. Public health
      interventions must target this group, particularly women.

PMID- 16614344
TI  - Fertility decline, family structure, and support for older persons in Latin
      America and Asia.
AB  - OBJECTIVE: To compare family structures and support for older persons in two
      Asian countries (Taiwan and the Philippines) and six urban areas in Latin America
      (Buenos Aires, Sao Paulo, Havana, Santiago, Mexico City, and Montevideo).
      METHODS: Using the 1999 Survey of Health and Living Status of the Elderly in
      Taiwan, the 2000 Philippine Survey of the Near Elderly and Elderly, and the 2001
      Pan American Health Organisation surveys on Salud, Bienestar y Envejecimiento en
      America Latina y el Caribe, descriptive tables show variations across countries
      in family structure, proximity, and transfers of support by the timing of the
      fertility transition in each location. RESULTS: Older people in settings with
      earlier transitions had fewer children and more childlessness, higher levels of
      solitary living, and lower levels of co-residence with children. In earlier
      transition settings, receipt of family support was lower and provision higher.
      DISCUSSION: The timing of the demographic transition has significant implications
      for kin availability and support.

PMID- 16614345
TI  - Comparative analysis of cognitive impairment among Mexicans and Spanish-speaking
      immigrant's elders.
AB  - OBJECTIVE: This study aims to compare the prevalence of cognitive impairment
      among older Mexicans and Spanish-speaking U.S. immigrants. METHODS: The
      relationship of cognitive impairment with social and demographic variables was
      explored using data from five different population based survey studies. RESULTS:
      Prevalence rates increased with age, with low educational level, didn't show a
      clear association with gender and decreased in married subjects. Estimates of
      cognitive and functional impairment combined are greater in the immigrant samples
      than those for Mexican residents. Primary memory measures are the least
      discriminative for cognitive impairment, whereas orientation, attention, and
      secondary verbal memory measures discriminate better. DISCUSSION: Mexicans and
      Spanish-speaking USA immigrants have similar prevalence estimates of cognitive
      impairment. However, prevalence of functional impairment differs between Mexicans
      and immigrants because of measurement issues and cultural factors.

PMID- 16614346
TI  - Comorbidity and disability in elderly Mexican and Mexican American adults:
      findings from Mexico and the southwestern United States.
AB  - This article aims to compare the effects of morbid and comorbid medical
      conditions on disability in elderly Mexican and Mexican American adults. Data
      from the 2001 Mexican Health and Aging Study (N = 4,872) and 1993 to 1994
      Hispanic Established Population for Epidemiologic Studies of the Elderly (N =
      3,050) were analyzed. Prevalence of medical conditions and disability in
      activities of daily living were calculated and logistic models were used to test
      associations. Prevalence of disability in older Mexicans was 16.3% while it was
      slightly lower in Mexican Americans (13.1%). Prevalence of arthritis, cancer,
      diabetes, heart attack, and stroke were substantially higher in Mexican Americans
      than in older adults living in Mexico. Diabetes, stroke, and heart attack were
      comorbid conditions that raised the likelihood of disability in both populations
      among subjects with other medical conditions. Despite differences in prevalence,
      the associations of morbidity and comorbidity with disability had similar
      magnitudes in both populations.

PMID- 16614347
TI  - Relative corticosteroid insensitivity of peripheral blood mononuclear cells in
      severe asthma.
AB  - RATIONALE AND OBJECTIVES: Patients with severe asthma have a poor therapeutic
      response to corticosteroid therapy, and corticosteroid responsiveness cannot be
      easily measured in these patients. We hypothesized that this poor response is
      associated with a reduced effect of corticosteroids to inhibit cytokine release
      from activated peripheral blood mononuclear cells (PBMCs). METHODS: Patients with
      severe asthma were defined by American Thoracic Society criteria. We compared the
      suppression of LPS-induced cytokine release (monocyte chemotactic protein-1 [MCP
      1], macrophage inflammatory protein [MIP] 1alpha, RANTES, tumor necrosis factor
      alpha, interleukin 1beta (IL-1beta), IL-8, IFN-gamma, IL-6, IL-10, and
      granulocyte-macrophage colony-stimulating factor [GM-CSF]) by dexamethasone from
      PBMCs of patients with severe asthma (n = 16), patients with nonsevere asthma (n
      = 19), and normal volunteers (n = 10). RESULTS: There was no difference in
      baseline spontaneous or stimulated release of these cytokines among groups. LPS
      induced release of 10 cytokines was less suppressed by dexamethasone (10(-6) M)
      in patients with severe asthma compared with patients with nonsevere asthma, with
      statistical significance achieved for IL-1beta (p < 0.03), IL-8 (p < 0.03), and
      MIP-1alpha (p < 0.003), and borderline significance for IL-6 (p = 0.054). There
      was less difference between the two groups for dexamethasone at 10(-8) M. Nuclear
      histone deacetylase (HDAC) and histone acetyltransferase activities were reduced
      in patients with severe asthma compared with patients with nonsevere asthma (p <
      0.01). HDAC activity reduction correlated directly to the degree of steroid
      insensitivity of GM-CSF (r = 0.57, p < 0.01) and IFN-gamma (r = 0.56, p < 0.05)
      release. Reduction in histone acetyltransferase activity related to
      corticosteroid use rather than asthma severity. CONCLUSIONS: Patients with severe
      asthma have diminished corticosteroid sensitivity of PBMCs when compared with
      patients with nonsevere asthma, associated with a reduction in HDAC activity that
      parallels the impaired corticosteroid sensitivity.

PMID- 16614348
TI  - Endotoxin exposure, CD14, and allergic disease: an interaction between genes and
      the environment.
AB  - RATIONALE: High endotoxin exposure may reduce the risk of allergic sensitization.
      OBJECTIVE: To determine the relationship between a promoter polymorphism in the
      CD14 gene (CD14/-159 C to T) and endotoxin exposure in relation to the
      development of allergic sensitization, eczema, and wheeze within the setting of a
      birth cohort. METHODS: We genotyped 442 children (CD14/-159 C to T; rs2569190).
      We assessed children for allergic sensitization (IgE > 0.2 kU/L to at least one
      of seven allergens), eczema (physical examination), and parentally reported
      wheeze. Endotoxin was measured in house dust. MAIN RESULTS: Genotype frequencies
      were consistent with other populations (TT, 25%; CT, 47%; CC, 28%). Sensitization
      (present in 33% of children) was not associated with genotype. For children with
      TT and CT genotypes, there was no association between endotoxin and sensitization
      (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.71-1.23; p = 0.7; and OR,
      0.90; 95% CI, 0.77-1.04; p = 0.16, respectively) or endotoxin and eczema (OR,
      0.99; 95% CI, 0.81-1.20; p = 0.89; and OR, 1.38; 95% CI, 0.83-2.30; p = 0.22,
      respectively). In children with the genotype CC, increasing endotoxin load was
      associated with a marked and significant reduction in the risk of sensitization
      (OR, 0.70; 95% CI, 0.55-0.89; p = 0.004) and eczema (OR, 0.73; 95% CI, 0.56-0.95;
      p = 0.02). However, we observed an increased risk of nonatopic wheeze with
      increasing endotoxin exposure in children with the CC genotype (OR, 1.42; 95% CI,
      1.01-1.99; p = 0.04) but not other genotypes. No effect was seen for atopic
      wheeze. CONCLUSIONS: Increasing endotoxin exposure is associated with reduced
      risk of allergic sensitization and eczema but with increased risk of nonatopic
      wheeze in children with the CC genotype at -159 of the CD14 gene. The impact of
      environmental endotoxin may be enhanced in individuals with this genotype.

PMID- 16614349
TI  - Long-term oxygen treatment in chronic obstructive pulmonary disease:
      recommendations for future research: an NHLBI workshop report.
AB  - Long-term oxygen treatment (LTOT) prolongs life in patients with chronic
      obstructive pulmonary disease (COPD) and severe resting hypoxemia. Although this
      benefit is proven by clinical trials, scientific research has not provided
      definitive guidance regarding who should receive LTOT and how it should be
      delivered. Deficiencies in knowledge and in current research activity related to
      LTOT are especially striking in comparison to the importance of LTOT in the
      management of COPD and the associated costs. The National Heart, Lung, and Blood
      Institute, in collaboration with the Centers for Medicare and Medicaid Services,
      convened a working group to discuss research on LTOT. Participants in this
      meeting identified specific areas in which further investigation would likely
      lead to improvements in the care of patients with COPD or reductions in the cost
      of their care. The group recommended four clinical trials in subjects with COPD:
      (1) efficacy of ambulatory O(2) supplementation in subjects who experience
      oxyhemoglobin desaturation during physical activity but are not severely
      hypoxemic at rest; (2) efficacy of LTOT in subjects with severe COPD and only
      moderate hypoxemia; (3) efficacy of nocturnal O(2) supplementation in subjects
      who show episodic desaturation during sleep that is not attributable to
      obstructive sleep apnea; and (4) effectiveness of an activity-dependent
      prescription for O(2) flow rate that is based on clinical tests performed at
      rest, during exercise, and during sleep.

PMID- 16614350
TI  - Transcription factors T-bet and GATA-3 regulate development of airway remodeling.
AB  - RATIONALE: Airway remodeling is an important feature of chronic asthma that
      causes irreversible airflow obstruction. Although asthma is considered to be a
      Th2 disease, the role of T-bet and GATA-3, the key transcription factors for
      differentiation toward Th1 and Th2 cells, in the pathogenesis of airway
      remodeling is poorly understood. OBJECTIVES: We therefore examined the effects of
      GATA-3 or T-bet induction of Th1/Th2 bias on the development of airway remodeling
      in mice. METHODS: The development of airway remodeling after repeated allergen
      challenges was analyzed using transgenic mice overexpressing either GATA-3 or T
      bet. MAIN RESULTS: The degrees of subepithelial fibrosis and airway smooth muscle
      hyperplasia after repeated allergen exposure were significantly enhanced in mice
      overexpressing GATA-3, compared with wild-type mice. Allergen-induced goblet cell
      hyperplasia and mucus hypersecretion were significantly lower in mice
      overexpressing T-bet than in wild-type mice. Eosinophilic airway inflammation
      increased in mice overexpressing GATA-3, but decreased in mice overexpressing T
      bet after repeated allergen exposure. Cytokine analysis revealed that the Th1/Th2
      cytokine balance shifted to Th2 in lung homogenates and lung T cells of mice
      overexpressing GATA-3, whereas this balance shifted to Th1 in those of mice
      overexpressing T-bet after allergen exposure. Lung transforming growth factor
      beta and eotaxin levels were associated with the degree of subepithelial fibrosis
      and eosinophilic airway inflammation, respectively. CONCLUSIONS: Overall, the
      results indicate that development of airway remodeling is regulated by the lung
      Th1/Th2 bias induced by GATA-3 and T-bet.

PMID- 16614351
TI  - Pulmonary neuroendocrine cells, airway innervation, and smooth muscle are altered
      in Cftr null mice.
AB  - The amine- and peptide-producing pulmonary neuroendocrine cells (PNEC) are widely
      distributed within the airway mucosa of mammalian lung as solitary cells and
      innervated clusters, neuroepithelial bodies (NEB), which function as airway O2
      sensors. These cells express Cftr and hence could play a role in the
      pathophysiology of cystic fibrosis (CF) lung disease. We performed confocal
      microscopy and morphometric analysis on lung sections from Cftr-/- (null),
      Cftr+/+, and Cftr+/- (control) mice at developmental stages E20, P5, P9, and P30
      to determine the distribution, frequency, and innervation of PNEC/NEB,
      innervation and cell mass of airway smooth muscle, and neuromuscular junctions
      using synaptic vesicle protein 2, smooth muscle actin, and synaptophysin markers,
      respectively. The mean number of PNEC/NEB in Cftr-/- mice was significantly
      reduced compared with control mice at E20, whereas comparable or increased
      numbers were observed postnatally. NEB cells in Cftr null mice showed a
      significant reduction in intracorpuscular nerve endings compared with control
      mice, which is consistent with an intrinsic abnormality of the PNEC system. The
      airways of Cftr-/- mice showed reduced density (approximately 20-30%) of smooth
      muscle innervation, decreased mean airway smooth muscle mass (approximately 35%),
      and reduced density (approximately 20%) of nerve endings compared with control
      mice. We conclude that the airways of Cftr-/- mice exhibit heretofore
      unappreciated structural alterations affecting cellular and neural components of
      the PNEC system and airway smooth muscle and its innervation resulting in blunted
      O2 sensing and reduced airway tonus. Cftr could play a role in the development of
      the PNEC system, lung innervation, and airway smooth muscle.

PMID- 16614353
TI  - Single muscle fiber adaptations with marathon training.
AB  - The purpose of this investigation was to characterize the effects of marathon
      training on single muscle fiber contractile function in a group of recreational
      runners. Muscle biopsies were obtained from the gastrocnemius muscle of seven
      individuals (22 +/- 1 yr, 177 +/- 3 cm, and 68 +/- 2 kg) before, after 13 wk of
      run training, and after 3 wk of taper. Slow-twitch myosin heavy chain [(MHC) I]
      and fast-twitch (MHC IIa) muscle fibers were analyzed for size, strength (P(o)),
      speed (V(o)), and power. The run training program led to the successful
      completion of a marathon (range 3 h 56 min to 5 h 35 min). Oxygen uptake during
      submaximal running and citrate synthase activity were improved (P < 0.05) with
      the training program. Muscle fiber size declined (P < 0.05) by approximately 20%
      in both fiber types after training. P(o) was maintained in both fiber types with
      training and increased (P < 0.05) by 18% in the MHC IIa fibers after taper. This
      resulted in >60% increase (P < 0.05) in force per cross-sectional area in both
      fiber types. Fiber V(o) increased (P < 0.05) by 28% in MHC I fibers with training
      and was unchanged in MHC IIa fibers. Peak power increased (P < 0.05) in MHC I and
      IIa fibers after training with a further increase (P < 0.05) in MHC IIa fiber
      power after taper. These data show that marathon training decreased slow-twitch
      and fast-twitch muscle fiber size but that it maintained or improved the
      functional profile of these fibers. A taper period before the marathon further
      improved the functional profile of the muscle, which was targeted to the fast
      twitch muscle fibers.

PMID- 16614352
TI  - Respiratory epithelial gene expression in patients with mild and severe cystic
      fibrosis lung disease.
AB  - Despite having identical cystic fibrosis transmembrane conductance regulator
      genotypes, individuals with DeltaF508 homozygous cystic fibrosis (CF) demonstrate
      significant variability in severity of pulmonary disease. This investigation used
      high-density oligonucleotide microarray analysis of nasal respiratory epithelium
      to investigate the molecular basis of phenotypic differences in CF by (1)
      identifying differences in gene expression between DeltaF508 homozygotes in the
      most severe 20th percentile of lung disease by forced expiratory volume in 1 s
      and those in the most mild 20th percentile of lung disease and (2) identifying
      differences in gene expression between DeltaF508 homozygotes and age-matched non
      CF control subjects. Microarray results from 23 participants (12 CF, 11 non-CF)
      met the strict quality control guidelines and were used for final data analysis.
      A total of 652 of the 11,867 genes identified as present in 75% of the samples
      were significantly differentially expressed in one of the three disease
      phenotypes: 30 in non-CF, 53 in mild CF, and 569 in severe CF. An analysis of
      genes differentially expressed by severity of CF lung disease demonstrated
      significant upregulation in severe CF of genes involved in protein ubiquination
      (P < 0.04), mitochondrial oxidoreductase activity (P < 0.01), and lipid
      metabolism (P < 0.03). Analysis of genes with decreased expression in patients
      with CF compared with control subjects demonstrated significant downregulation of
      genes involved in airway defense (P < 0.047) and protein metabolism (P < 0.048).
      This study suggests that differences in CF lung phenotype are associated with
      differences in expression of genes involving airway defense, protein
      ubiquination, and mitochondrial oxidoreductase activity and identifies specific
      new candidate modifiers of the CF phenotype.

PMID- 16614354
TI  - ACE inhibition prevents myocardial infarction-induced skeletal muscle
      mitochondrial dysfunction.
AB  - Heart failure is associated with alterations in cardiac and skeletal muscle
      energy metabolism resulting in a generalized myopathy. We investigated the
      molecular and cellular effects of angiotensin-converting enzyme inhibition (ACEi)
      on skeletal muscle metabolism in infarcted animals. Myocardial infarction (MI)
      was obtained by left descending coronary artery ligation. Sham, MI, and MI
      treated rats (perindopril, 2 mg.kg(-1).day(-1) given 7 days after MI) were
      studied 1 and 4 mo after surgery. Oxygen consumption of white gastrocnemius (Gas)
      muscle was studied in saponin-permeabilized fibers, using the main substrates of
      mitochondrial respiration. mRNA expression of nuclear factors (PGC-1alpha, NRF
      2alpha, and mtTFA), involved in the transcription of mitochondrial proteins, and
      of MCIP1, a marker of calcineurin activation, were also determined.
      Echocardiographic left ventricular fractional shortening was reduced in both MI
      and perindopril group after 1 and 4 mo, whereas systemic blood pressure was
      reduced by 16% only in the MI group after 4 mo. The capacity of Gas to oxidize
      glutamate-malate, glycerol-triphosphate, or pyruvate (-30%, P < 0.01; -32%, P <
      0.05; -33%, P < 0.01, respectively), was greatly decreased. Furthermore, PGC
      1alpha (-54%), NRF-2alpha (-45%), and MCIP1 (-84%) gene expression were
      significantly downregulated. ACEi improved survival, left ventricular function,
      and blood pressure. Perindopril protected also totally the Gas mitochondrial
      function and preserved the mRNAs concentration of the mitochondrial
      transcriptional factors. Moreover, PGC-1alpha correlated with Gas oxidative
      capacity (r = 0.48), mitochondrial cytochrome-c oxidase (r = 0.65), citrate
      synthase (r = 0.45) activities, and MCIP1 expression (r = 0.44). Thus ACEi
      totally prevented MI-induced alterations of skeletal muscle mitochondrial
      function and protein expression, halting the development of this metabolic
      myopathy.

PMID- 16614355
TI  - Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic
      mechanisms in young vs. older adults.
AB  - Resistance training (RT) has shown the most promise in reducing/reversing effects
      of sarcopenia, although the optimum regime specific for older adults remains
      unclear. We hypothesized myofiber hypertrophy resulting from frequent (3 days/wk,
      16 wk) RT would be impaired in older (O; 60-75 yr; 12 women, 13 men), sarcopenic
      adults compared with young (Y; 20-35 yr; 11 women, 13 men) due to slowed
      repair/regeneration processes. Myofiber-type distribution and cross-sectional
      area (CSA) were determined at 0 and 16 wk. Transcript and protein levels of
      myogenic regulatory factors (MRFs) were assessed as markers of regeneration at 0
      and 24 h postexercise, and after 16 wk. Only Y increased type I CSA 18% (P <
      0.001). O showed smaller type IIa (-16%) and type IIx (-24%) myofibers before
      training (P < 0.05), with differences most notable in women. Both age groups
      increased type IIa (O, 16%; Y, 25%) and mean type II (O, 23%; Y, 32%) size (P <
      0.05). Growth was generally most favorable in young men. Percent change scores on
      fiber size revealed an age x gender interaction for type I fibers (P < 0.05) as
      growth among Y (25%) exceeded that of O (4%) men. Myogenin and myogenic
      differentiation factor D (MyoD) mRNAs increased (P < 0.05) in Y and O, whereas
      myogenic factor (myf)-5 mRNA increased in Y only (P < 0.05). Myf-6 protein
      increased (P < 0.05) in both Y and O. The results generally support our
      hypothesis as 3 days/wk training led to more robust hypertrophy in Y vs. O,
      particularly among men. However, this differential hypertrophy adaptation was not
      explained by age variation in MRF expression.

PMID- 16614356
TI  - Role of nitric oxide in the regulation of digital pulse volume amplitude in
      humans.
AB  - Measurement of the increase in digital pulse volume amplitude (PVA) during
      reactive hyperemia relative to baseline (PVA-RH) is being applied widely as a
      convenient test of nitric oxide bioavailability. However, evidence linking
      digital PVA-RH to nitric oxide is currently lacking. Accordingly, we investigated
      whether nitric oxide is responsible for the increase in digital PVA. During
      reactive hyperemia, we used a peripheral arterial tonometer to record digital PVA
      at baseline and during reactive hyperemia. The role of nitric oxide in these
      responses was investigated in 19 healthy subjects by inhibiting nitric oxide
      synthesis with N(G)-nitro-L-arginine methyl ester (L-NAME). Ten subjects
      underwent the identical protocol with saline and five with phenylephrine, a
      nonspecific vasoconstrictor, instead of L-NAME. The change in digital PVA after
      drug administration was compared between the three groups. Relative to the
      response with saline (-5 +/- 2%), baseline PVA was unchanged by L-NAME infusion (
      10 +/- 2%), but it decreased significantly with phenylephrine (-50 +/- 12%; P =
      0.003). PVA-RH increased slightly with saline infusion (9 +/- 4%). In comparison,
      PVA-RH was significantly blunted by L-NAME administration (-46 +/- 21%; P =
      0.002) and was relatively unchanged by phenylephrine (20 +/- 9%). The present
      study establishes a central role for nitric oxide in the augmentation of PVA
      during reactive hyperemia. The measurement of digital PVA-RH may indeed provide a
      simple means of assessing endothelial function in humans.

PMID- 16614357
TI  - Thermal effects of whole head submersion in cold water on nonshivering humans.
AB  - This study isolated the effect of whole head submersion in cold water, on surface
      heat loss and body core cooling, when the confounding effect of shivering heat
      production was pharmacologically eliminated. Eight healthy male subjects were
      studied in 17 degrees C water under four conditions: the body was either
      insulated or uninsulated, with the head either above the water or completely
      submersed in each body-insulation subcondition. Shivering was abolished with
      buspirone (30 mg) and meperidine (2.5 mg/kg), and subjects breathed compressed
      air throughout all trials. Over the first 30 min of immersion, exposure of the
      head increased core cooling both in the body-insulated conditions (head out: 0.47
      +/- 0.2 degrees C, head in: 0.77 +/- 0.2 degrees C; P < 0.05) and the body
      exposed conditions (head out: 0.84 +/- 0.2 degrees C and head in: 1.17 +/- 0.5
      degrees C; P < 0.02). Submersion of the head (7% of the body surface area) in the
      body-exposed conditions increased total heat loss by only 10%. In both body
      exposed and body-insulated conditions, head submersion increased core cooling
      rate much more (average of 42%) than it increased total heat loss. This may be
      explained by a redistribution of blood flow in response to stimulation of
      thermosensitive and/or trigeminal receptors in the scalp, neck and face, where a
      given amount of heat loss would have a greater cooling effect on a smaller
      perfused body mass. In 17 degrees C water, the head does not contribute
      relatively more than the rest of the body to surface heat loss; however, a cold
      induced reduction of perfused body mass may allow this small increase in heat
      loss to cause a relatively larger cooling of the body core.

PMID- 16614358
TI  - Bimodal distribution of vasodilator responsiveness to adenosine due to difference
      in nitric oxide contribution: implications for exercise hyperemia.
AB  - To gain insight into the role of adenosine (Ado) in exercise hyperemia, we
      compared forearm vasodilation induced by intra-arterial infusion of three doses
      of Ado with vasodilation during three workloads of forearm handgrip exercise in
      27 human subjects. We measured forearm blood flow (FBF) using Doppler ultrasound
      and mean arterial pressure (MAP) via brachial artery catheters and calculated
      forearm vascular conductance (FVC = FBF/MAP) during each infusion dose or
      workload. We found that about half of the subjects demonstrated robust
      vasodilator responsiveness to both Ado infusion and exercise, and the other half
      demonstrated blunted vasodilator responsiveness to Ado infusion compared with
      exercise. In 15 subjects (identified as "Ado responders"), the change in FVC
      above baseline was 209 +/- 33, 419 +/- 57, and 603 +/- 75 ml.min(-1).100 mmHg(-1)
      for the low, medium, and high doses of Ado, respectively, and 221 +/- 35, 413 +/-
      54, and 582 +/- 70 ml.min(-1).100 mmHg(-1) for the low, medium, and high exercise
      workloads, respectively. In the other 12 subjects (identified as "Ado
      nonresponders"), the change in FVC above baseline was 102 +/- 36, 113 +/- 42, and
      151 +/- 54 ml.min(-1).100 mmHg(-1) for the low, medium, and high doses of Ado,
      respectively (P < 0.05 vs. Ado responders), whereas exercise hyperemia was not
      different from Ado responders (P > 0.05). Furthermore, infusion of NG-monomethyl
      L-arginine (L-NMMA) blunted vasodilator responses to Ado infusion only in Ado
      responders (P < 0.01 vs. post-L-NMMA) and had no effect on exercise in either
      group. We also found differences in vasodilator responses to isoproterenol at all
      doses, but acetylcholine only at one dose, between Ado responders and
      nonresponders. We conclude that vasodilator responsiveness to Ado exhibits a
      bimodal distribution among human subjects involving differences in the
      contribution of nitric oxide to Ado-mediated vasodilation. Finally, our data
      support the concept that neither Ado nor nitric oxide is obligatory for exercise
      hyperemia.

PMID- 16614359
TI  - Castration prevents suppression of MHC class II (Ia) expression on macrophages
      after trauma-hemorrhage.
AB  - Several studies indicate that cell-mediated immune responses, i.e., macrophage
      (MPhi) cytokine release capacities, myosin heavy chain (MHC) class II (Ia)
      expression, etc., are suppressed after trauma-hemorrhage in male mice.
      Testosterone has been shown to be responsible for the depression of MPhi cytokine
      responses in males after trauma-hemorrhage. Antigen presentation via MHC class II
      plays a key role in initiating and maintaining cell-mediated and humoral immune
      responses. It remains unknown, however, whether testosterone has any effect on
      MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were
      castrated or sham castrated 2 wk before trauma (midline laparotomy) and
      hemorrhage (Hem; blood pressure 35 +/- 5 mmHg for 90 min and resuscitation) or
      sham operation. Four hours thereafter, MHC class II (Ia) expression was measured
      using flow cytometry. The results indicate that MHC class II (Ia) expression on
      peritoneal and splenic MPhi was significantly suppressed in male mice after
      trauma-hemorrhage. Prior castration, however, prevented the depression in MHC
      class II (Ia) expression on peritoneal and splenic MPhi after trauma-hemorrhage.
      Castration did not affect MHC class II (Ia) expression in MPhi from sham
      castrated mice. Thus testosterone depresses MHC class II (Ia) expression on
      peritoneal and splenic MPhi after trauma-hemorrhage in males. Because MHC class
      II is necessary for an adequate immune response, our results suggest that
      depletion of male sex steroids or blockade of androgen receptors using agents
      such as flutamide might prevent immunosuppression via maintaining MHC class II
      (Ia) expression after trauma and severe blood loss.

PMID- 16614360
TI  - Possible new mechanism underlying hypertonic saline therapy for cerebral edema.

PMID- 16614361
TI  - Physical activity and dietary intervention for chronic diseases: a quick fix
      after all?

PMID- 16614362
TI  - Breaking the rules for bone adaptation to mechanical loading.

PMID- 16614363
TI  - Does blood flow restriction enhance hypertrophic signaling in skeletal muscle?

PMID- 16614364
TI  - Respiratory and circulatory effects of parietal pleural afferent stimulation in
      rabbits.
AB  - Respiratory symptoms accompanying pleural diseases combine dyspnea, tachypnea,
      rapid shallow breathing, and sometimes hypotension. There are no experimental
      data on the changes in respiratory and circulatory functions elicited by the
      activation of pleural afferents. After removal of all muscles covering the 5th to
      10th intercostal spaces, we investigated in paralyzed, vagotomized rabbits the
      changes in phrenic discharge, transpulmonary pressure, and systemic arterial
      pressure in response to an outwardly directed force exerted on the parietal
      pleura or the local application of solutions containing lactic acid or
      inflammatory mediators. Mechanical stimulation of the pleura induced an immediate
      decrease in both integrated phrenic discharge and arterial blood pressure, the
      responses being positively correlated with the magnitude of force applied on the
      pleura. No accompanying changes in ventilatory timing, transpulmonary pressure,
      or heart rate were measured. Lactic acid solution also elicited an inhibition of
      phrenic activity and a fall in blood pressure. Section of the internal
      intercostal nerves supplying the stimulated intercostal spaces totally abolished
      the responses to mechanical stimulation or lactic acid. An inflammatory mixture
      elicited only modest respiratory and circulatory effects. We concluded that an
      acute mechanical distension of the parietal pleura as well as its chemical
      stimulation by lactic acid elicit a marked inhibition of phrenic motoneurons
      combined to a reduction of the sympathetic outflow to the circulatory system.

PMID- 16614365
TI  - A simplified noninvasive method to measure airway blood flow in humans.
AB  - Our laboratory has previously developed and validated a noninvasive soluble gas
      uptake method to measure airway blood flow (Qaw) in humans (Onorato DJ, Demirozu
      MC, Breitenbucher A, Atkins ND, Chediak AD, and Wanner A. Am J Respir Crit Care
      Med 149: 1132-1137, 1994; Scuri M, McCaskill V, Chediak AD, Abraham WM, and
      Wanner A. J Appl Physiol 79: 1386-1390, 1995). The method has the disadvantage of
      requiring eight breath-hold maneuvers for a single Qaw measurement, a complicated
      data analysis, and the inhalation of a potentially explosive gas mixture
      containing dimethylether (DME) and O2. Because of these shortcomings, the method
      thus far has not been used in other laboratories. We now simplified the method by
      having the subjects inhale 500 ml of a 10% DME-90% N2 gas mixture to fill the
      anatomical dead space, followed by a 5- or 15-s breath hold, and measuring the
      instantaneous DME and N2 concentrations and volume at the airway opening during
      the subsequent exhalation. From the difference in DME concentration in phase 1 of
      the expired N2 wash-in curve multiplied by the phase 1 dead space volume and
      divided by the mean DME concentration and the solubility coefficient for DME in
      tissue, Qaw can be calculated by using Fick's equation. We compared the new
      method to the validated old method in 10 healthy subjects and found mean +/- SE
      Qaw values of 34.6 +/- 2.3 and 34.6 +/- 2.8 microl.min(-1).ml(-1), respectively
      (r = 0.93; upper and lower 95% confidence limit +2.48 and -2.47). Using the new
      method, the mean coefficient of variation for two consecutive measurements was
      4.4% (range 0-10.4%); inhalation of 1.2 mg albuterol caused a 53 +/- 14% increase
      in Qaw (P = 0.02) and inhalation of 2.4 mg methoxamine caused a 32 +/- 7%
      decrease in Qaw (P = 0.07). We conclude that the new method provides reliable
      values of and detects the expected changes in Qaw with vasoactive drugs. The
      simplicity and improved safety of the method should improve its acceptability for
      the noninvasive assessment of Qaw in clinical research.

PMID- 16614366
TI  - Neural control and mechanisms of eccrine sweating during heat stress and
      exercise.
AB  - In humans, evaporative heat loss from eccrine sweat glands is critical for
      thermoregulation during exercise and/or exposure to hot environmental conditions,
      particularly when environmental temperature is greater than skin temperature.
      Since the time of the ancient Greeks, the significance of sweating has been
      recognized, whereas our understanding of the mechanisms and controllers of
      sweating has largely developed during the past century. This review initially
      focuses on the basic mechanisms of eccrine sweat secretion during heat stress
      and/or exercise along with a review of the primary controllers of
      thermoregulatory sweating (i.e., internal and skin temperatures). This is
      followed by a review of key nonthermal factors associated with prolonged heat
      stress and exercise that have been proposed to modulate the sweating response.
      Finally, mechanisms pertaining to the effects of heat acclimation and
      microgravity exposure are presented.

PMID- 16614367
TI  - Shivering in the cold: from mechanisms of fuel selection to survival.
AB  - In cold-exposed adult humans, significant or lethal decreases in body temperature
      are delayed by reducing heat loss via peripheral vasoconstriction and by
      increasing rates of heat production via shivering thermogenesis. This brief
      review focuses on the mechanisms of fuel selection responsible for sustaining
      long-term shivering thermogenesis. It provides evidence to explain large
      discrepancies in fuel selection measurements among shivering studies, and it
      proposes links between choices in fuel selection mechanism and human survival in
      the cold. Over the last decades, a number of studies have quantified the
      contributions of carbohydrate (CHO) and lipid to total heat generation. However,
      the exact contributions of these fuels still remain unclear because of large
      differences in fuel selection measurements even at the same metabolic rate.
      Recent advances on the mechanisms of fuel selection during shivering provide some
      plausible explanations for these discrepancies between shivering studies. This
      new evidence indicates that muscles can sustain shivering over several hours
      using a variety of fuel mixtures achieved by modifying diet (changing the size of
      CHO reserves) or by changing muscle fiber recruitment (increasing or decreasing
      the recruitment of type II fibers). From a practical perspective, how does the
      choice of fuel selection mechanism affect human survival in the cold? Based on a
      glycogen-depletion model, estimates of shivering endurance show that, whereas the
      oxidation of widely different fuel mixtures does not improve survival time, the
      selective recruitment of fuel-specific muscle fibers provides a substantial
      advantage for cold survival. By combining fundamental research on fuel metabolism
      and applied strategies to improve shivering endurance, future research in this
      area promises to yield important new information on what limits human survival in
      the cold.

PMID- 16614368
TI  - In vivo mechanisms of cutaneous vasodilation and vasoconstriction in humans
      during thermoregulatory challenges.
AB  - This review focuses on the neural and local mechanisms that have been
      demonstrated to effect cutaneous vasodilation and vasoconstriction in response to
      heat and cold stress in vivo in humans. First, our present understanding of the
      mechanisms by which sympathetic cholinergic nerves mediate cutaneous active
      vasodilation during reflex responses to whole body heating is discussed. These
      mechanisms include roles for cotransmission as well as nitric oxide (NO). Next,
      the mechanisms by which sympathetic noradrenergic nerves mediate cutaneous active
      vasoconstriction during whole body cooling are reviewed, including cotransmission
      by neuropeptide Y (NPY) acting through NPY Y1 receptors. Subsequently, current
      concepts for the mechanisms that effect local cutaneous vascular responses to
      direct skin warming are examined. These mechanisms include the roles of
      temperature-sensitive afferent neurons as well as NO in causing vasodilation
      during local heating of skin. This section is followed by a review of the
      mechanisms that cause local cutaneous vasoconstriction in response to direct
      cooling of the skin, including the dependence of these responses on intact
      sensory and sympathetic, noradrenergic innervation as well as roles for nonneural
      mechanisms. Finally, unresolved issues that warrant further research on
      mechanisms that control cutaneous vascular responses to heating and cooling are
      discussed.

PMID- 16614369
TI  - In health and in a normoxic environment, VO2 max is/is not limited primarily by
      cardiac output and locomotor muscle blood flow.

PMID- 16614370
TI  - Supraspinal locomotor centers do/do not contribute significantly to the hyperpnea
      of dynamic exercise in humans.

PMID- 16614371
TI  - Abcg5/Abcg8-independent pathways contribute to hepatobiliary cholesterol
      secretion in mice.
AB  - The ATP-binding cassette (ABC) half-transporters ABCG5 and ABCG8 heterodimerize
      into a functional complex that mediates the secretion of plant sterols and
      cholesterol by hepatocytes into bile and their apical efflux from enterocytes. We
      addressed the putative rate-controlling role of Abcg5/Abcg8 in hepatobiliary
      cholesterol excretion in mice during (maximal) stimulation of this process.
      Despite similar bile salt (BS) excretion rates, basal total sterol and
      phospholipid (PL) output rates were reduced by 82% and 35%, respectively, in chow
      fed Abcg5(-/-) mice compared with wild-type mice. When mice were infused with the
      hydrophilic BS tauroursodeoxycholate, similar relative increases in bile flow, BS
      output, PL output, and total sterol output were observed in wild-type, Abcg5(+/
      ), and Abcg5(-/-) mice. Maximal cholesterol and PL output rates in Abcg5(-/-)
      mice were only 15% and 69%, respectively, of wild-type values. An infusion of
      increasing amounts of the hydrophobic BS taurodeoxycholate increased cholesterol
      excretion by 3.0- and 2.4-fold in wild-type and Abcg5(-/-) mice but rapidly
      induced cholestasis in Abcg5(-/-) mice. Treatment with the liver X receptor (LXR)
      agonist T0901317 increased the maximal sterol excretion capacity in wild-type
      mice (fourfold), concomitant with the induction of Abcg5/Abcg8 expression, but
      not in Abcg5(-/-) mice. In a separate study, mice were fed chow containing 1%
      (wt/wt) cholesterol. As expected, hepatic expression of Abcg5 and Abcg8 was
      strongly induced (fivefold and fourfold) in wild-type but not LXR-alpha-deficient
      (Lxra(-/-)) mice. Surprisingly, hepatobiliary cholesterol excretion was increased
      to the same extent, i.e., 2.2-fold in wild-type mice and 2.0-fold in Lxra(-/-)
      mice, upon cholesterol feeding. Our data confirm that Abcg5, as part of the
      Abcg5/Abcg8 heterodimer, strongly controls hepatobiliary cholesterol secretion in
      mice. However, our data demonstrate that Abcg5/Abcg8 heterodimer-independent,
      inducible routes exist that can significantly contribute to total hepatobiliary
      cholesterol output.

PMID- 16614372
TI  - Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory
      response after hemorrhagic shock and resuscitation.
AB  - Hemorrhagic shock and resuscitation cause endotoxemia and hepatocellular damage.
      Because lipopolysaccharide-binding protein (LBP) enhances cellular responses to
      endotoxin, our aim was to determine whether LBP contributes to
      hemorrhage/resuscitation-induced injury by comparing LBP knockout and wild-type
      mice. Under pentobarbital anaesthesia, wild-type and LBP-deficient mice were
      hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood plus half
      the volume of lactated Ringer solution. Serum alanine aminotransferase (ALT)
      necrosis, neutrophil infiltration, and 4-hydroxynonenal by
      histology/cytochemistry and stress kinase activation by immunoblot analysis were
      then determined. ALT in wild-type mice was 2,461 +/- 383 and 1,418 +/- 194 IU/l
      (means +/- SE), respectively, at 2 and 6 h after resuscitation versus sham ALT of
      102 +/- 6 IU/l. In LBP-deficient mice, ALT was blunted at both time points to
      1,108 +/- 340 and 619 +/- 171 IU/l (P < 0.05). Liver necrosis after 6 h was also
      attenuated from 3.5 +/- 0.8% in wild-type mice to 1.3 +/- 0.5% in LBP-deficient
      mice (P < 0.05). After hemorrhage/resuscitation, neutrophil infiltration
      increased 71% more in wild-type than LBP knockout mice. Similarly, hepatic 4
      hydroxynonenal staining, indicative of lipid peroxidation, decreased from 33.8 +/
      4.5% in wild-type mice to 11.6 +/- 1.9% in knockout mice (P < 0.05). After
      hemorrhage/resuscitation, activation of MAPKs, JNK and ERK, occurred in wild-type
      mice, which was largely blocked in LBP-deficient mice. However, endotoxin in
      portal blood after resuscitation was not significantly different between wild
      type and knockout mice. In conclusion, hemorrhagic shock and resuscitation to
      mice cause severe, LBP-mediated hepatocellular damage. An absence of LBP blunts
      hepatocellular injury with decreased neutrophil infiltration, oxidative stress,
      and c-Jun and ERK activation.

PMID- 16614373
TI  - ANIT toxicity toward mouse hepatocytes in vivo is mediated primarily by
      neutrophils via CD18.
AB  - Alpha-naphthylisothiocyanate (ANIT) is a hepatotoxicant that causes acute
      cholestatic hepatitis with infiltration of neutrophils around bile ducts and
      necrotic hepatocytes. The objective of this study was to determine whether the
      beta2-integrin CD18, which plays an important role in leukocyte invasion and
      cytotoxicity, contributes to ANIT-induced hepatic inflammation and liver injury.
      Mice with varying levels of leukocyte CD18 expression were treated with ANIT and
      monitored for hepatic neutrophil influx and liver injury over 48 h. Mice that
      were partially deficient in CD18 (30% of normal levels) developed periportal
      inflammation and widespread hepatic necrosis after ANIT treatment in a pattern
      identical to that in wild-type (WT) mice. In contrast, mice that completely lack
      CD18 (CD18 null) were resistant to ANIT toxicity. Forty-eight hours after ANIT,
      CD18-null mice displayed 60% lower serum alanine aminotransferase (ALT) levels
      and 75% less hepatic necrosis, as shown by morphometry, than WT mice. This was
      true despite evidence that ANIT still provoked hepatic neutrophil influx in CD18
      null mice. WT mice could also be protected from ANIT-induced hepatocellular
      necrosis, by depleting the animals of neutrophils. Notably, neither CD18-null
      mice nor neutrophil-depleted WT mice exhibited any attenuation of bile duct
      injury or cholestasis due to ANIT. We conclude from these experiments that
      neutrophils invade ANIT-treated livers in a CD18-independent fashion but utilize
      CD18 to induce hepatocellular cytotoxicity. The results emphasize that neutrophil
      mediated amplification of ANIT-induced liver injury is directed toward
      hepatocytes rather than cholangiocytes. In fact, the data indicate that the
      majority of ANIT toxicity toward hepatocytes in vivo is neutrophil driven.

PMID- 16614374
TI  - Effect of luminal acidity on the apical cation channel in rabbit esophageal
      epithelium.
AB  - Esophageal epithelial cells contain an apical cation channel that actively
      absorbs sodium ions (Na(+)). Since these channels are exposed in vivo to acid
      reflux, we sought the impact of high acidity on Na(+) channel function in Ussing
      chambered rabbit epithelium. Serosal nystatin abolished short-circuit current
      (I(sc)) and luminal pH titrated from pH 7.0 to pH > or = 2.0 had no effect on
      I(sc). Circuit analysis at pH 2.0 showed small, but significant, increases in
      apical and shunt resistances. At pH < 2.0, I(sc) increased whereas resistance
      (R(T)) decreased along with an increase in fluorescein flux. The change in I(sc),
      but not R(T), was reversible at pH 7.4. Reducing pH from 7.0 to 1.1 with
      H(2)SO(4) gave a similar pattern but higher I(sc) values, suggesting shunt
      permselectivity. A 10:1 Na(+) gradient after nystatin increased I(sc) by
      approximately 4 muAmps/cm(2) and this declined at pH < or = 3.5 until it reached
      approximately 0.0 at pH 2.0. Impedance analysis on acid-exposed (non-nystatin
      treated) tissues showed compensatory changes in apical (increase) and basolateral
      (decrease) resistance at modest luminal acidity that were poorly reversible at pH
      2.0 and associated with declines in capacitance, a reflection of lower apical
      membrane area. In esophageal epithelium apical cation channels transport Na(+) at
      gradients as low as 10:1 but do not transport H(+) at gradients of 100,000:1
      (luminal pH 2.0). Luminal acid also inhibits Na(+) transport via the channels and
      abolishes it at pH 2.0. These effects on the channel may serve as a protective
      function for esophageal epithelium exposed to acid reflux.

PMID- 16614375
TI  - Impaired mucus-bicarbonate barrier in Helicobacter pylori-infected mice.
AB  - To resist the harsh intrinsic milieu, several lines of defense exist in the
      stomach. The aim of this study was to investigate the effect of the gastric
      pathogen Helicobacter pylori on these mechanisms in vivo. We used FVB/N mice
      expressing human alpha-1,3/4-fucosyl transferase (producing Lewis b epitopes) and
      inoculated with H. pylori 1. Mice were anesthetized with isoflurane or Hypnorm
      midazolam, the stomach was exteriorized, and the surface of the corpus mucosa was
      exposed. Mucus thickness was measured with micropipettes, juxtamucosal pH
      (pH(jm)) was measured with pH-sensitive microelectrodes, blood flow was measured
      with laser-Doppler flowmetry, and mRNA levels of the bicarbonate transporter
      SLC26A9 were quantified with real-time PCR. The increase in mucosal blood flow
      seen in response to luminal acid (pH 1.5) in control animals (140 +/- 9% of
      control) was abolished in infected mice. The firmly adherent mucus layer was
      significantly thinner in infected mice (31 +/- 2 microm) than in control mice (46
      +/- 5 microm), and no mucus accumulation occurred in infected mice. pH(jm)
      decreased significantly more on exposure to luminal acid in infected mice
      (luminal pH 1.5, pH(jm) 2.4 +/- 0.7) than in control mice (pH(jm) 6.4 +/- 0.5).
      Despite reduced pH(jm), SLC26A9 mRNA expression was significantly, by increased
      1.9-fold, in infected mice. The reduction in pH(jm) by infection with H. pylori
      might be due to a reduced firmly adherent mucus layer, increased mucus
      permeability to H(+), and/or inhibition of bicarbonate transport. The
      upregulation of SLC26A9 in H. pylori-infected epithelium might be a result of
      continuous inhibition of the transporter, e.g., by ammonium, a H. pylori product,
      which has been previously shown to inhibit SLC26A9.

PMID- 16614376
TI  - New literacies, multiple literacies, unlimited literacies: what now, what next,
      where to? A response to blue listerine, parochialism and ASL literacy.
AB  - This article is a response to Blue Listerine, Parochialism, and ASL Literacy
      (Czubek, 2006). The author presents his views on the concepts of literacy and the
      new and multiple literacies. In addition, the merits of print literacy and other
      types of literacies are discussed. Although the author agrees that there is an
      American Sign Language (ASL) literacy, he maintains that there should be a
      distinction between conversational "literacy" forms (speech and sign) and
      secondary literacy forms (reading and writing). It might be that cognitive skills
      associated with print literacy and, possibly, other captured literacy forms, are
      necessary for a technological, scientific-driven society such as that which
      exists in the United States.

PMID- 16614377
TI  - Phylogeny and evolution of class-I helical cytokines.
AB  - The class-I helical cytokines constitute a large group of signalling molecules
      that play key roles in a plethora of physiological processes including host
      defence, immune regulation, somatic growth, reproduction, food intake and energy
      metabolism, regulation of neural growth and many more. Despite little primary
      amino acid sequence similarity, the view that all contemporary class-I helical
      cytokines have expanded from a single ancestor is widely accepted, as all class-I
      helical cytokines share a similar three-dimensional fold, signal via related
      class-I helical cytokine receptors and activate similar intracellular signalling
      cascades. Virtually all of our knowledge on class-I helical cytokine signalling
      derives from research on primate and rodent species. Information on the presence,
      structure and function of class-I helical cytokines in non-mammalian vertebrates
      and non-vertebrates is fragmentary. Consequently, our ideas about the evolution
      of this versatile multigene family are often based on a limited comparison of
      human and murine orthologs. In the last 5 years, whole genome sequencing projects
      have yielded draft genomes of the early vertebrates, pufferfish (Takifugu
      rubripes), spotted green pufferfish (Tetraodon nigroviridis) and zebrafish (Danio
      rerio). Fuelled by this development, fish orthologs of a number of mammalian
      class-I helical cytokines have recently been discovered. In this review, we have
      characterised the mammalian class-I helical cytokine family and compared it with
      the emerging class-I helical cytokine repertoire of teleost fish. This approach
      offers important insights into cytokine evolution as it identifies the helical
      cytokines shared by fish and mammals that, consequently, existed before the
      divergence of teleosts and tetrapods. A 'fish-mammalian' comparison will identify
      the class-I helical cytokines that still await discovery in fish or,
      alternatively, may have been evolutionarily recent additions to the mammalian
      cytokine repertoire.

PMID- 16614378
TI  - Depletion of resting zone chondrocytes during growth plate senescence.
AB  - With age, the growth plate undergoes senescent changes that cause linear bone
      growth to slow and finally cease. Based on previous indirect evidence, we
      hypothesized that this senescent decline occurs because growth plate stem-like
      cells, located in the resting zone, have a finite proliferative capacity that is
      gradually depleted. Consistent with this hypothesis, we found that the
      proliferation rate in rabbit resting zone chondrocytes (assessed by continuous 5
      bromo-2'-deoxy-uridine labeling) decreases with age, as does the number of
      resting zone chondrocytes per area of growth plate. Glucocorticoid excess slows
      growth plate senescence. To explain this effect, we hypothesized that
      glucocorticoid inhibits resting zone chondrocyte proliferation, thus conserving
      their proliferative capacity. Consistent with this hypothesis, we found that
      dexamethasone treatment decreased the proliferation rate of rabbit resting zone
      chondrocytes and slowed the numerical depletion of these cells. Estrogen is known
      to accelerate growth plate senescence. However, we found that estradiol cypionate
      treatment slowed resting zone chondrocyte proliferation. Our findings support the
      hypotheses that growth plate senescence is caused by qualitative and quantitative
      depletion of stem-like cells in the resting zone and that growth-inhibiting
      conditions, such as glucocorticoid excess, slow senescence by slowing resting
      zone chondrocyte proliferation and slowing the numerical depletion of these
      cells, thereby conserving the proliferative capacity of the growth plate. We
      speculate that estrogen might accelerate senescence by a proliferation
      independent mechanism, or by increasing the loss of proliferative capacity per
      cell cycle.

PMID- 16614379
TI  - Differential involvement of nuclear factor-kappaB and activator protein-1
      pathways in the interleukin-1beta-mediated decrease of deiodinase type 1 and
      thyroid hormone receptor beta1 mRNA.
AB  - One of the hallmarks of the sick euthyroid syndrome or non-thyroidal illness is a
      decrease of serum triiodothyronine, caused mainly by a decrease in liver
      deiodinase type 1 (D1) mRNA and activity. Proinflammatory cytokines like
      interleukin (IL)-1beta are likely involved in this disease, but are also known to
      inhibit thyroid hormone receptor (TR)-beta1 gene expression, which is of interest
      as the D1 promoter contains TREs. The aim of the present study was to evaluate
      whether the IL-1beta-induced decrease of D1 and TRbeta1 mRNA is mediated by the
      same cytokine signalling pathways in a human hepatoma cell line (HepG2). We
      observed a downregulation of both D1 and TRbeta1 mRNA after 4 h of incubating the
      cells with IL-1beta. Sulfasalazine was used to inhibit the nuclear factor-kappaB
      (NFkappaB) pathway and SP600125, a chemical inhibitor of the c-Jun N-terminal
      kinase, was used as an inhibitor of the activator protein-1 (AP-1) pathway. AP-1
      inhibition did not affect the decrease of D1 and TRbeta1 mRNA, but the TRbeta1
      mRNA decrease was completely abolished after inhibiting NFkappaB, while D1 mRNA
      was unaffected. Only simultaneous inhibition of both the NFkappaB and AP-1
      pathways abolished the D1 mRNA decrease. We concluded that IL-1beta stimulation
      of HepG2 cells results in a marked decrease of D1 and TRbeta1 mRNA. The decrease
      of TRbeta1 mRNA is exclusively mediated by the NFkappaB pathway, while the
      decrease of D1 mRNA requires inhibition of both the AP-1 and the NFkappaB
      pathways.

PMID- 16614380
TI  - Integrative study of hypothalamus-pituitary-thyroid-immune system interaction:
      thyroid hormone-mediated modulation of lymphocyte activity through the protein
      kinase C signaling pathway.
AB  - Thyroid hormones play critical roles in differentiation, growth and metabolism,
      but their participation in immune system regulation has not been completely
      elucidated. Modulation of in vivo thyroid status was used to carry out an
      integrative analysis of the role of the hypothalamus-pituitary-thyroid (HPT) axis
      in T and B lymphocyte activity. The participation of the protein kinase C (PKC)
      signaling pathway and the release of some cytokines upon antigenic stimulation
      were analyzed. Lymphocytes from hyperthyroid mice displayed higher T-and B-cell
      mitogen-induced proliferation, and those from hypothyroid mice displayed lower T-
      and B-cell mitogen-induced proliferation, compared with euthyroid animals.
      Reversion of hypothyroid state by triiodothyronine (T3) administration recovered
      the proliferative responses. No differences were found in lymphoid subset
      balance. Both total PKC content and mitogen-induced PKC translocation were higher
      in T and B cells from hyperthyroid mice, and lower in cells from hypothyroid
      mice, compared with controls. Levels of thyroid-stimulating (TSH) and TSH
      releasing (TRH) hormones were not directly related to lymphocyte proliferative
      responses. After immunization with sheep red blood cells (SRBCs) and re
      stimulation, in vitro spleen cells from hyper- or hypothyroid mice showed,
      respectively, increased or decreased production of interleukin (IL)-2 and
      interferon (IFN)-gamma cytokines. Additionally, an increase in IL-6 and IFN-gamma
      levels was found in hyperthyroid cells after in vivo injection and in vitro re
      stimulation with lipopolysaccharide (LPS). Our results show for the first time a
      thyroid hormone-mediated regulation of PKC content and of cytokine production in
      lymphocytes; this regulation could be involved in the altered responsiveness to
      mitogen-induced proliferation of T and B cells. The results also confirm the
      important role that these hormones play in regulating lymphocyte reactivity.

PMID- 16614381
TI  - Ghrelin stimulates phagocytosis and superoxide production in fish leukocytes.
AB  - To clarify the role of ghrelin in the fish immune system, the in vitro effect of
      ghrelin was examined in phagocytic leukocytes of rainbow trout (Oncorhynchus
      mykiss). Administration of trout ghrelin and des-VRQ-trout ghrelin, in which
      three amino acids are deleted from trout ghrelin, increased superoxide production
      in zymosan-stimulated phagocytic leukocytes from the head kidney. Gene expression
      of growth hormone (GH) secretagogue-receptor (GHS-R) was detected by RT-PCR in
      leukocytes. Pretreatment of phagocytic leukocytes with a GHS-R antagonist, [D
      Lys3]-GHRP-6, abolished the stimulatory effects of trout ghrelin and des-VRQ
      trout ghrelin on superoxide production. Ghrelin increased mRNA levels of
      superoxide dismutase and GH expressed in trout phagocytic leukocytes.
      Immunoneutralization of GH by addition of anti-salmon GH serum to the medium
      blocked the stimulatory effect of ghrelin on superoxide production. These results
      suggest that ghrelin stimulates phagocytosis in fish leukocytes through a GHS-R
      dependent pathway, and also that the effect of ghrelin is mediated, at least in
      part, by GH secreted by leukocytes.

PMID- 16614382
TI  - Ghrelin enhances glucose-induced insulin secretion in scheduled meal-fed sheep.
AB  - The purpose of this study was to investigate the effects of physiologic levels of
      ghrelin on insulin secretion and insulin sensitivity (glucose disposal) in
      scheduled fed-sheep, using the hyperglycemic clamp and hyperinsulinemic
      euglycemic clamp respectively. Twelve castrated Suffolk rams (69.8 +/- 0.6 kg)
      were conditioned to be fed alfalfa hay cubes (2% of body weight) once a day.
      Three hours after the feeding, synthetic ovine ghrelin was intravenously
      administered to the animals at a rate of 0.025 and 0.05 mug/kg body weight (BW)
      per min for 3 h. Concomitantly, the hyperglycemic clamp or the hyperinsulinemic
      euglycemic clamp was carried out. In the hyperglycemic clamp, a target glucose
      concentration was clamped at 100 mg/100 ml above the initial level. In the
      hyperinsulinemic euglycemic clamp, insulin was intravenously administered to the
      animals for 3 h at a rate of 2 mU/kg BW per min. Basal glucose concentrations
      (44+/- 1 mg/dl) were maintained by variably infusing 100 mg/dl glucose solution.
      In both clamps, plasma ghrelin concentrations were dose-dependently elevated and
      maintained at a constant level within the physiologic range. Ghrelin infusions
      induced a significant (ANOVA; P < 0.01) increase in plasma GH concentrations. In
      the hyperglycemic clamp, plasma insulin levels were increased by glucose infusion
      and were significantly (P < 0.05) greater in ghrelin-infused animals. In the
      hyperinsulinemic euglycemic clamp, glucose infusion rate, an index of insulin
      sensitivity, was not affected by ghrelin infusion. In conclusion, the present
      study has demonstrated for the first time that ghrelin enhances glucose-induced
      insulin secretion in the ruminant animal.

PMID- 16614383
TI  - Effects of long-term treatment with resveratrol and subcutaneous and oral
      estradiol administration on pituitary function in rats.
AB  - Hormone replacement therapy (HRT) has been used for several decades to treat
      menopausal discomforts. However, in the light of recent studies that draw
      attention to the potential hazards of conventional HRT, various attempts have
      been undertaken to search for alternatives to classical HRT. Phytoestrogens are
      claimed to be capable of positively influencing menopausal symptoms, including
      hot flushes. We designed a long-term study of 3 months to assess the effects of
      subcutaneous and orally fed 17beta-estradiol (E2), as well as the actions of
      resveratrol (RES) on pituitary function in female rats. Our results have
      demonstrated that RES binds with a 10-fold lower affinity to estrogen receptor
      (ER)-alpha than to ERbeta. The data from the in vivo study revealed that a dosage
      of 5 microg and 50 microg RES/kg bodyweight per day given to ovariectomized (OVX)
      rats achieved serum levels of 1.0 and 8.1 microM respectively. Long-term
      treatment of OVX rats with RES revealed no estrogenic potential on pituitary
      function in vivo as assessed by LH and prolactin secretion and by regulation of
      mRNAs for LHalpha, LHbeta, and GnRH receptor. Subcutaneous treatment with E2 in
      silastic capsules exerted stronger effects on LH and prolactin secretion, as well
      as on LHbeta, LHalpha, GnRH receptor, and ERbeta mRNA regulation compared with
      orally applied estradiol benzoate despite comparable serum levels. Levels of aryl
      hydrocarbon receptor (AhR) mRNA in the pituitary were increased following OVX and
      attenuated by long-term E2 treatment, whereas RES did not modulate AhR mRNA
      expression.

PMID- 16614384
TI  - Differential expression and regulation of prostaglandin E synthases in the mouse
      ovary during sexual maturation and luteal development.
AB  - Prostaglandin (PGE) 2 is the most common prostanoid and plays an important role
      in female reproduction. The aim of this study was to examine the expression and
      regulation of microsomal (m) PGE synthase (PGES)-1 and cytosolic (c) PGES in the
      mouse ovary during sexual maturation, gonadotropin treatment and luteal
      development by in situ hybridization and immunohistochemistry. Both mPGES-1 mRNA
      signals and immunostaining were localized in the granulosa cells, but not in the
      thecal cells and oocytes. cPGES mRNA signals were localized in both granulosa
      cells and oocytes, whereas cPGES immunostaining was exclusively localized in the
      oocytes. In our superovulated model of immature mice, there was a basal level of
      mPGES-1 mRNA signals in the granulosa cells at 48 h after equine chorionic
      gonadotropin (eCG) treatment. mPGES-1 mRNA level was induced by human chorionic
      gonadotropin (hCG) treatment for 0.5 h, whereas mPGES-1 immunostaining was
      slightly induced at 0.5 h after hCG treatment and reached a maximal level at 3 h
      after hCG treatment. eCG treatment had no obvious effects on either cPGES mRNA
      signals or immunostaining. A strong level of cPGES immunostaining was present in
      both unstimulated and eCG-treated groups. Both mPGES-1 mRNA signals and
      immunostaining were highly detected in the corpus luteum 2 days post-hCG
      injection and declined from days 3 to 7 post-hCG injection. cPGES immunostaining
      was at a basal level or not detectable from days 1 to 7 after hCG injection and
      was highly expressed in the corpus luteum from days 9 to 15 post-hCG injection.
      PGE2 biosynthesized through the mPGES-1 pathway may be important for follicular
      development, ovulation and luteal formation.

PMID- 16614385
TI  - The influence of sex steroid hormones on ferrochelatase gene expression in
      Harderian gland of hamster (Mesocricetus auratus).
AB  - Ferrochelatase (protohaem ferrolyase, EC 4.99.1.1), the terminal enzyme of the
      haem biosynthetic pathway, catalyses the insertion of ferrous iron into
      protoporphyrin IX to form protohaem. The Syrian hamster Harderian gland (HG) is
      known for its ability to produce and accumulate large amounts of protoporphyrins.
      In this species, the female gland contains up to 120 times more porphyrin than
      the male gland. Data from biochemical studies suggest that this gland possesses
      the enzymatic complex for haem biosynthesis but lacks ferrochelatase activity.
      The abundance of intraglandular haem proteins does not support this idea. To gain
      more insight into this process, we isolated cDNA for ferrochelatase from hamster
      liver, using the 5'- and 3'- rapid amplification of complementary DNA ends
      (RACE), and investigated its expression in HG from males and females. The full
      length cDNA comprises an open reading frame of 1269 bp encoding a polypeptide of
      422 amino-acid residues. Hamster DNA sequence exhibits 92% identity to mouse and
      87% identity to human sequences. The predicted hamster enzyme was shown to have
      structural features of mammalian ferrochelatase, including a putative NH2-
      terminal presequence, a central core of about 330 amino-acid residues and an
      extra 30-50-amino-acid stretch at the carboxyl-terminus. RNA blotting experiments
      indicated that this cDNA hybridized to a liver mRNA of about 2.1 kb, while a weak
      hybridization signal was observed with mRNA from HG preparations. RT-PCR assays
      confirmed the expression of specific transcripts in both tissues. Male glands
      contained approximately twofold more enzyme mRNA than female glands. Likewise,
      the intraglandular content of mRNA varied during the oestrous cycle, with the
      highest levels found in the oestrous phase. These cyclic variations were less
      evident in liver. Ovariectomy plus treatment with progesterone or 17beta
      oestradiol plus progesterone increased ferrochelatase mRNA of the gland. In HG of
      short- or long-term castrated males, the administration of testosterone did not
      affect the ferrochelatase mRNA concentration. Based on mRNA expression levels, we
      conclude that Harderian ferrochelatase may play an active role in maintaining the
      physiological pool of haem required for processing cytochromes and other
      glandular haem proteins. Likewise, the sex-steroid hormones appear to have only a
      modest influence upon Harderian ferrochelatase.

PMID- 16614386
TI  - The activin-follistatin system and in vitro early follicle development in goats.
AB  - The aim of the present study was to investigate the effects of activin-A and
      follistatin on in vitro primordial and primary follicle development in goats. To
      study primordial follicle development (experiment 1), pieces of ovarian cortex
      were cultured in vitro for 5 days in minimal essential medium (MEM) supplemented
      with activin-A (0, 10 or 100 ng/ml), follistatin (0, 10 or 100 ng/ml) or
      combinations of the two. After culture, the numbers of primordial follicles and
      more advanced follicle stages were calculated and compared with those in non
      cultured tissue. Protein and mRNA expression of activin-A, follistatin, Kit
      ligand (KL), growth differentiation factor-9 (GDF-9) and bone morphogenetic
      protein-15 (BMP-15) in non-cultured and cultured follicles were studied by
      immunohistochemistry and PCR. To evaluate primary follicle growth (experiment 2),
      freshly isolated follicles were cultured for 6 days in MEM plus 100 ng/ml activin
      A, 100 ng/ml follistatin or 100 ng/ml activin-A plus 200 ng/ml follistatin.
      Morphology, follicle and oocyte diameters in cultured tissue and isolated
      follicles before and after culture were assessed. Terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labelling (TUNEL) reactions were performed to
      study DNA fragmentation in follicles. In experiment 1, it was found that goat
      primordial follicles were activated to develop into more advanced stages, i.e.
      intermediate and primary follicles, during in vitro culture, but neither activin
      A nor follistatin affected the number of primordial follicles that entered the
      growth phase. Activin-A treatment enhanced the number of morphologically normal
      follicles and stimulated their growth during cortical tissue culture. The effects
      were, however, not counteracted by follistatin. The follicles in cultured goat
      tissue maintained their expression of proteins and mRNA for activin-A,
      follistatin, KL, GDF-9 and BMP-15. Fewer than 30% of the atretic follicles in
      cultured cortical tissue had TUNEL-positive (oocyte or granulosa) cells. Activin
      A did not affect the occurrence of TUNEL-positive cells in follicles within
      cortical tissue. In experiment 2, addition of activin-A to cultured isolated
      primary follicles significantly stimulated their growth, the effect being
      counteracted by follistatin. Absence of such a neutralizing effect of follistatin
      in the cultures with ovarian cortical tissue can be due to lower dose of
      follistatin used and incomplete blockage of activin in these experiments. In
      contrast to cortical enclosed atretic follicles, all atretic follicles that had
      arisen in cultures with isolated primary follicles had TUNEL-positive cells,
      which points to differences between isolated and ovarian tissue-enclosed
      follicles with regard to the followed pathways leading to their degeneration. In
      summary, this in vitro study has demonstrated that cultured goat primordial
      follicles are activated to grow and develop into intermediate and primary
      follicles. During in vitro culture, the follicles maintain their ability to
      express activin-A, follistatin, KL, GDF-9 and BMP-15. The in vitro growth and
      survival of activated follicles enclosed in cortical tissue and the in vitro
      growth of isolated primary follicles are stimulated by activin-A.

PMID- 16614387
TI  - Ocimum sanctum leaf extracts stimulate insulin secretion from perfused pancreas,
      isolated islets and clonal pancreatic beta-cells.
AB  - Ocimum sanctum leaves have previously been reported to reduce blood glucose when
      administered to rats and humans with diabetes. In the present study, the effects
      of ethanol extract and five partition fractions of O. sanctum leaves were studied
      on insulin secretion together with an evaluation of their mechanisms of action.
      The ethanol extract and each of the aqueous, butanol and ethylacetate fractions
      stimulated insulin secretion from perfused rat pancreas, isolated rat islets and
      a clonal rat beta-cell line in a concentration-dependent manner. The stimulatory
      effects of ethanol extract and each of these partition fractions were potentiated
      by glucose, isobutylmethylxanthine, tolbutamide and a depolarizing concentration
      of KCl. Inhibition of the secretory effect was observed with diazoxide, verapamil
      and Ca2+ removal. In contrast, the stimulatory effects of the chloroform and
      hexane partition fractions were associated with decreased cell viability and were
      unaltered by diazoxide and verapamil. The ethanol extract and the five fractions
      increased intracellular Ca2+ in clonal BRIN-BD11 cells, being partly attenuated
      by the addition of verapamil. These findings indicated that constituents of O.
      sanctum leaf extracts have stimulatory effects on physiological pathways of
      insulin secretion which may underlie its reported antidiabetic action.

PMID- 16614388
TI  - Hepatocyte growth factor modulates in vitro survival and proliferation of germ
      cells during postnatal testis development.
AB  - The hepatocyte growth factor (HGF) is a pleiotropic cytokine that influences
      mitogenesis, motility and differentiation of many different cell types by its
      tyrosine kinase receptor c-Met. We previously demonstrated that the c-Met/HGF
      system is present and functionally active during postnatal testis development. We
      found also that spermatozoa express c-Met and that HGF has a positive effect on
      the maintenance of sperm motility. In the present paper, we extend our study on
      the germ cells at different stages of differentiation during the postnatal
      development of the testis. We demonstrate that c-met is present in rat
      spermatogonia, pachytene spermatocytes and round spermatids and that HGF
      significantly increases spermatogonial proliferation in 8- to 10-day-old pre
      pubertal rats. At this age HGF does not affect Sertoli cells and peritubular
      myoid cells proliferation. In addition, we studied the effect of the factor on
      germ cell apoptosis and we show that HGF prevents the germ cell apoptotic
      process. We also studied the effect of HGF on 18- to 20-day-old and 28- to 30-day
      old rat testes. At these ages also the factor significantly increases germ cell
      duplication and decreases the number of apoptotic cells. However, the effect on
      programmed cell death is higher in the 8- to 10-day-old rats and declines in the
      older animals. In conclusion, we report that rat germ cells (spermatogonia,
      pachytene spermatocytes and round spermatids) express c-met and that HGF
      modulates germ cell proliferating activity and apoptosis in vitro. These data
      indicate that the c-Met/HGF system is involved in male germ cell homeostasis and,
      consequently, has a role in male fertility.

PMID- 16614389
TI  - A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression,
      IGF-I production and body weight gain in normal mice.
AB  - Diabetic retinopathy and acromegaly are diseases associated with excess action of
      GH and its effector IGF-I, and there is a need for improved therapies. We have
      designed an optimised 2'-O-(2-methoxyethyl)-modified phosphorothioate
      oligodeoxynucleotide, ATL 227446, and demonstrated its ability to suppress GH
      receptor mRNA in vitro. Subcutaneous injections of ATL 227446 reduced GH receptor
      mRNA levels, GH binding activity and serum IGF-I levels in mice after seven days
      of dosing. The reduction in serum IGF-I could be sustained for over ten weeks of
      dosing at therapeutically relevant levels, during which there was also a
      significant decrease in body weight gain in antisense-treated mice relative to
      saline and mismatch control-treated mice. The findings indicate that
      administration of an antisense oligonucleotide to the GH receptor may be
      applicable to human diseases in which suppression of GH action provides
      therapeutic benefit.

PMID- 16614390
TI  - Atrial natriuretic peptide modulates cystic fibrosis transmembrane conductance
      regulator chloride channel expression in rat proximal colon and human intestinal
      epithelial cells.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is one of the most
      intensively investigated Cl- channels. Different mutations in the CFTR gene cause
      the disease cystic fibrosis (CF). CFTR is expressed in the apical membrane of
      various epithelial cells including the intestine. The major organ affected in CF
      patients is the lung, but it also causes an important dysfunction of intestinal
      ion transport. The modulation of CFTR mRNA expression by atrial natriuretic
      peptide (ANP) was investigated in rat proximal colon and in human intestinal CaCo
      2 cells by RNase protection assay and semi-quantitative reverse transcriptase PCR
      techniques. Groups of rats subjected to volume expansion or intravenous infusion
      of synthetic ANP showed respective increases of 60 and 50% of CFTR mRNA
      expression in proximal colon. CFTR mRNA was also increased in cells treated with
      ANP, reaching a maximum effect at 10(-9) M ANP, probably via cGMP. ANP at 10(-9)
      M was also able to stimulate both the CFTR promoter region (by luciferase assay)
      and protein expression in CaCo-2 cells (by Western blot and
      immunoprecipitation/phosphorylation). These results suggested the involvement of
      ANP, a hormone involved with extracellular volume, in the expression of CFTR in
      rat proximal colon and CaCo-2 intestinal cells.

PMID- 16614391
TI  - Expression of urocortin in rat lung and its effect on pulmonary vascular
      permeability.
AB  - Urocortin (UCN), a newly identified, 40-amino-acid, corticotropin-releasing
      hormone (CRH) structurally related peptide, has been demonstrated to be expressed
      in the central nervous system and many peripheral tissues of rats and man. This
      study aimed to investigate the expression profile of UCN in rat lung and the
      effect of UCN on lung vascular permeability. The expression of UCN mRNA was
      detected by reverse transcriptase PCR (RT-PCR). UCN peptide was measured by
      immunohistochemistry and Western blot analysis. We found that both UCN mRNA and
      peptide were obviously expressed in rat lung. Immunohistochemistry results showed
      that UCN peptide is mainly expressed in bronchial epithelium mucosa and alveolar
      epithelium. We also found that rats receiving inhalation aerosol of UCN had a
      significant elevation of lung vascular permeability compared with rats receiving
      vehicle and ovalbumin (OVA) by the Evans blue (EB) technique. UCN aerosol
      inhalation resulted in obvious pulmonary congestion and edema observed under
      light microscope by hematoxylin and eosin (HE) staining. The nonselective peptide
      CRH receptor antagonist astressin markedly reduced lung vascular permeability
      triggered by UCN. Enhanced pulmonary vascular permeability induced by UCN was
      markedly inhibited by pretreatment with the mast-cell stabilizer cromolyn and
      histamine-1 (H1) receptor antagonist azelastine respectively, but not by the
      leukotriene receptor antagonist montelukast. In summary, in the present study, we
      demonstrated for the first time that UCN is expressed in rat lung and contributes
      to an increase in lung vascular permeability through activation of CRH receptors.
      Mast cells and histamine may be involved in this effect of UCN. Peripherally
      produced UCN in lung may act as an autocrine and paracrine proinflammatory
      factor.

PMID- 16614392
TI  - Forkhead transcription factor FOXO1A is critical for induction of human
      decidualization.
AB  - Experiments utilizing RNA interference technology were performed to determine
      whether the forkhead transcription factor FOXO1A, a member of the FOXO family of
      proteins, plays a critical role in the induction of human uterine
      decidualization. Human decidual fibroblast cells were decidualized in vitro for 6
      days with medroxyprogester-one, estradiol, and dibutyryl cAMP in the presence or
      absence of a highly specific FOXO1A small interfering RNA (siRNA) that inhibits
      FOXO1A mRNA and protein expression by more than 80%. RNA and proteins were
      extracted from the cells at 0, 2, 4, and 6 days. FOXO1A and IGFBP-1 proteins were
      determined by immunoblotting; and intracellular mRNA levels for several
      decidualization marker genes were determined by real-time PCR. Exposure of the
      cells to FOXO1A siRNA in five separate experiments resulted in a 40-75%
      inhibition of prolactin, IGFBP-1, tissue inhibitor of metalloproteinase 3
      (TIMP3), somatostatin and endometrial bleeding-associated factor (EBAF) mRNAs,
      all of which are markedly induced during the decidualization process. In
      contrast, actin and GAPDH mRNA levels did not change during decidualization. The
      inhibition of mRNA levels was first noted at day 2 and persisted for the
      remainder of each experiment. Western blot analysis indicated that the FOXO1A
      siRNA inhibited IGFBP-1 protein expression by 60-80%. Decidual fibroblast cells
      exposed in an identical manner to a control RNA that had no effect on FOXO1A
      expression caused only a 0-15% inhibition of the marker genes and IGFBP-1
      protein. Taken together, these findings strongly suggest a critical role for
      FOXO1A in the induction of human decidualization.

PMID- 16614393
TI  - Lysophosphatidylethanolamine in Grifola frondosa as a neurotrophic activator via
      activation of MAPK.
AB  - We found that Grifola frondosa extracts induced the activation of mitogen
      activated protein kinase (MAPK) in cultured PC12 cells, a line of rat
      pheochromocytoma cells. The active substance was isolated by a few
      chromatographic steps, including high-performance liquid chromatography, and was
      identified to be lysophosphatidylethanolamine (LPE) from various structural
      analyses. LPE from G. frondosa (GLPE) was confirmed to induce the activation of
      MAPK of cultured PC12 cells and was found to suppress cell condensation and DNA
      ladder generation evoked by serum deprivation, suggesting that the GLPE had
      antiapoptotic effects. Moreover, GLPE caused morphological changes in and
      upregulation of neurofilament M expression of PC12 cells, demonstrating that the
      GLPE could induce neuronal differentiation of these cells. The activation of MAPK
      by GLPE was suppressed by AG1478, an antagonist of epidermal growth factor
      receptor (EGFR), and by U0126, an inhibitor of MAPK kinase (MEK1/2), but not by
      K252a, an inhibitor of TrkA, or by pertussis toxin. These results demonstrate
      that GLPE induced the MAPK cascade [EGFR-MEK1/2-extracellular signal-regulated
      protein kinases (ERK1/2)] of PC12 cells, the activation of which induced neuronal
      differentiation and suppressed serum deprivation-induced apoptosis. This study
      has clarified for the first time the involvement of the MAPK signal cascade in
      LPE actions.

PMID- 16614394
TI  - Malnutrition and energy restriction differentially affect viral immunity.
AB  - Protein-energy malnutrition is associated with a decrease in immunity and an
      increase in infectious disease. Both of these effects are exacerbated in aging.
      Conversely, energy restriction (ER) without malnutrition extends the lifespan in
      animals and retards the age-related decline in various parameters of immune
      function. Recent evidence suggests, however, that aged ER mice exhibit an
      increased mortality in response to primary influenza infection compared with age
      matched controls. Underweight may contribute to this outcome due to an inability
      to meet the energy demands associated with the immune response to primary viral
      infection. The energetic costs of immune responsiveness must be considered in the
      undernourished aging population and emerging studies of ER in humans.

PMID- 16614395
TI  - Hepatic gene regulation by glucose and polyunsaturated fatty acids: a role for
      ChREBP.
AB  - The liver is a major site for carbohydrate metabolism (glycolysis and glycogen
      synthesis) and triglyceride synthesis (lipogenesis). In the last decade,
      increasing evidence has emerged to show that nutrients, in particular, glucose
      and fatty acids, are able to regulate hepatic gene expression in a
      transcriptional manner. Indeed, although insulin was long thought to be the major
      regulator of hepatic gene expression, it is now clear that glucose metabolism
      rather that glucose itself also contributes substantially to the coordinated
      regulation of carbohydrate and lipid homeostasis in liver. In fact, the recent
      discovery of the glucose-signaling transcription factor carbohydrate responsive
      element binding protein (ChREBP) shed some light on the molecular mechanisms by
      which glycolytic and lipogenic genes are reciprocally regulated by glucose and
      fatty acids in liver. Here, we will review some of the recent studies that have
      begun to elucidate the regulation and function of this key transcription factor
      in liver. Indeed, a better understanding of the mechanisms by which glucose and
      fatty acids control hepatic gene expression may provide novel insight into the
      development of new therapeutic strategies for a better management of diseases
      involving blood glucose and/or disorders of lipid metabolism.

PMID- 16614396
TI  - Cocoa polyphenols inhibit phorbol ester-induced superoxide anion formation in
      cultured HL-60 cells and expression of cyclooxygenase-2 and activation of NF
      kappaB and MAPKs in mouse skin in vivo.
AB  - We investigated the antioxidant and antiinflammatory activities of a flavonoid
      rich polyphenolic fraction of cocoa. Cocoa polyphenol (CP) was fractionated from
      commercial cocoa powder and contained 468 mg/g of gallic acid-equivalent
      phenolics and 413 mg/g epicatechin-equivalent flavonoids. CP exhibited a dose
      dependent free radical-scavenging activity as determined by both 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) and 2,2'-diphenyl-1-picrylhydrazyl radical
      scavenging assays. CP also dose-dependently inhibited xanthine oxidase activity
      and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced superoxide-anion
      generation in cultured human promyeolcytic leukemia HL-60 cells. Oral
      administering of CP (4, 20, 40, and 200 mg/kg body weight) to ICR mice 1 h prior
      to TPA (10 nmol) inhibited ear edema at 5 h in a dose-dependent manner. The
      levels of COX-2 expression induced in mouse skin after 4-h treatment with topical
      TPA (10 nmol) was also diminished significantly by pretreating CP (40 or 200
      mg/kg) for 30 min. CP at the same doses inhibited TPA-induced nuclear
      translocation of p65 and subsequent DNA binding of NF-kappaB at 1 h by blocking
      the degradation of IkappaBalpha in mouse skin. Moreover, phosphorylation of p38
      mitogen-activated protein kinase in ICR mouse skin, measured 4 h after TPA
      treatment, was suppressed by oral pretreatment of CP (40 or 200 mg/kg). Although
      extracellular signal-regulated protein kinase 1/2 phosphorylation was unaffected,
      CP inhibited the catalytic activity of extracellular signal-regulated protein
      kinase 1/2 in TPA-stimulated mouse skin. Since cellular proinflammatory and
      prooxidant states are closely linked to tumor promotion, the antioxidant and
      antiinflammatory properties of CP may constitute the basis of possible antitumor
      promoting effects of this phytochemical.

PMID- 16614397
TI  - Tp53-associated growth arrest and DNA damage repair gene expression is attenuated
      in mammary epithelial cells of rats fed whey proteins.
AB  - Dietary protection from mammary cancer is likely coordinated through multiple
      signaling pathways, based on the known heterogeneity of the disease and the
      distinct origins of mammary tumor cells. The present study examined the
      modulatory effects of dietary intake of whey protein hydrolysate (WPH) relative
      to casein (CAS), on mammary epithelial cell resistance to endogenous DNA damage
      using Tp53 gene expression and signaling as a read-out, and on systemic
      proapoptotic and immune surveillance activity, in young adult female Sprague
      Dawley rats. Rats were fed AIN-93G diets made with CAS or WPH as the sole protein
      source beginning at gestation d 4. At postnatal day (PND) 50, mammary glands of
      rats fed WPH had lower levels of activated Tp53 and p38 mitogen-activated protein
      kinase proteins, and reduced transcript levels for Tp53-associated DNA damage
      repair, growth arrest, and proapoptotic genes than those of CAS-fed rats. Serum
      from WPH-fed rats had greater apoptotic activity in MCF-7 tumor cells than that
      from rats fed CAS. Serum levels of monocyte chemoattractant protein (MCP)-1 were
      higher in WPH- than in CAS-fed rats. MCF-7 cells treated with CAS serum +
      recombinant rat MCP-1 had apoptotic activity and Tp53 and p21 gene expression
      levels comparable to those treated with WPH serum or recombinant MCP-1. Results
      indicate that mammary glands of rats fed a WPH diet are more protected from
      endogenous DNA damage than are those of CAS-fed rats, and identify MCP-1 as a
      potential serum biomarker for the positive effects of healthy diets.

PMID- 16614398
TI  - The ABCG5 polymorphism contributes to individual responses to dietary cholesterol
      and carotenoids in eggs.
AB  - The ATP binding cassette G5 (ABCG5) polymorphisms have been postulated to play a
      role in the response to dietary cholesterol. The objective of this study was to
      examine the contribution of the ABCG5 polymorphism on the plasma response to
      consumption of cholesterol and carotenoids from eggs. For this purpose,
      genotyping was conducted for 40 men and 51 premenopausal women who were randomly
      assigned to consume an egg (EGG, 640 mg/d additional dietary cholesterol and 600
      microg lutein+ zeaxanthin) or placebo (SUB, 0 mg/d cholesterol, 0 microg lutein +
      zeaxanthin) diet for 30 d. The two arms of the dietary intervention were
      separated by a 3-wk washout period. Plasma concentrations of total cholesterol,
      LDL cholesterol (LDL-C), and HDL cholesterol were determined. Because eggs are an
      excellent source of lutein and zeaxanthin, the plasma levels of these carotenoids
      were also measured in a subset of subjects to determine whether the response to
      carotenoid intake was similar to that seen for dietary cholesterol and to
      evaluate the contribution of ABCG5 polymorphism to both responses. Individuals
      possessing the C/C genotype experienced a greater increase in both LDL-C (P <
      0.05) and a trend for lutein (P = 0.08) during the EGG period compared with those
      individuals with the C/G (heterozygote) or G/G genotypes (homozygotes). These
      results, although obtained from a small number of subjects, suggest that the
      ABCG5 polymorphism may play a role in the plasma response to dietary cholesterol
      and carotenoids.

PMID- 16614399
TI  - The soybean isoflavone genistein induces differentiation of MG63 human
      osteosarcoma osteoblasts.
AB  - A soybean-rich diet was shown to reduce the incidence of osteoporosis in Eastern
      countries; its effect on bone metabolism was ascribed to the action of the
      soybean isoflavones such as genistein. Although many studies have shown
      isoflavone-induced osteoblast differentiation, its preventative action on bone
      mass loss has not been clarified. Here, the osteogenetic effects of genistein on
      human cell line MG63 osteoblasts were elucidated using a variety of approaches.
      In particular, phalloidin-rhodamine staining revealed that genistein-treated
      osteoblasts possessed a more organized cytoskeleton, and genistein's inhibitory
      effect upon cell proliferation was associated with exposure of
      phosphatidylserines on the external plasmalemma surface. Although this
      phosphatidylserine exposure is considered a typical apoptotic marker, scanning
      and transmission electron microscopy revealed that genistein-treated osteoblasts
      released matrix vesicles and showed no evidence of chromatin condensation.
      Assays, stainings, and scanning electron microscopy showed that genistein-treated
      osteoblasts synthesized relatively high levels of collagen and alkaline
      phosphatase and, even in a nonosteogenic growth medium, formed mineralized bone
      noduli. A clear pattern of genistein-induced osteoblast activation therefore
      emerges, in which all of the essential components required for the rapid
      production of mineralized bone extracellular matrix are stimulated by this
      soybean isoflavone.

PMID- 16614400
TI  - Maternal iron deficiency identifies critical windows for growth and
      cardiovascular development in the rat postimplantation embryo.
AB  - Imbalances in nutrition during pregnancy can lead to long-, as well as short-term
      consequences, a phenomenon known as fetal programming. However, there is little
      information about when the fetus is most sensitive to its environment during
      gestation. We hypothesize that different fetal systems are most vulnerable to
      nutritional stress during periods of maximal growth and differentiation. We used
      iron (Fe) deficiency, which causes hypertension in the offspring, to test this
      hypothesis. We examined development between embryonic day (E) 10.5 and 12.5, when
      cardiovascular development is maximal, using whole embryo culture. Female rats
      were fed Fe-deficient or control diet for 4 wk before mating and up to E10.5. The
      embryos were cultured for 48 h in 95% rat serum collected from males fed either a
      control or Fe-deficient diet. Growth was impaired and heart size increased in
      embryos taken from Fe-deficient mothers and cultured in deficient serum compared
      with control embryos cultured in control serum. To test whether restoring normal
      Fe levels could reverse these effects, we cultured embryos from control and
      deficient dams in either control or deficient medium. The yolk sac circulation of
      embryos from dams fed either diet cultured in deficient medium was less
      developed, with a thinner and less branched network than that in all embryos
      cultured in control serum. The heart was enlarged in embryos of deficient dams
      cultured in deficient serum compared with the heart size of those cultured in
      control serum. Culturing embryos in control serum reversed these changes. We
      conclude, therefore, that this period of cardiovascular organogenesis is one of
      the sensitive windows during which optimal Fe status is critical for normal
      development.

PMID- 16614401
TI  - Quercetin inhibits eNOS, microtubule polymerization, and mitotic progression in
      bovine aortic endothelial cells.
AB  - Quercetin (QRN), one of the most abundant flavonoids in the human diet, is a
      known antioxidant and inhibitor of cancer cell cycle progression. Here, we
      provide the first evidence that QRN inhibits angiogenesis via a mechanism
      involving both suppression of endothelial nitric oxide synthase (eNOS) and early
      M-phase cell cycle arrest. Bovine aortic endothelial (BAE) cells were exposed to
      doses of up to 100 micromol/L QRN and assayed for eNOS activity and
      phosphorylation status. Phosphorylation of eNOS at Ser 617 (bovine sequence) is
      thought to occur in response to Akt stimulation and to be required for eNOS
      activity. Together with basal eNOS activity, eNOS phosphorylation at Ser 617 and
      Akt Ser 473 phosphorylation were dose dependently and concomitantly suppressed by
      QRN within 30 min. Furthermore, although the significant (P < 0.05) inhibitory
      effect of a single 100 micromol/L QRN dose on eNOS activity was overcome within
      approximately 24 h, chronic QRN exposures (24-48 h) led to early M-phase arrest
      and disruption of mitotic microtubule polymerization. In vivo, QRN administered
      i.p. to female Balb/C mice bearing both syngeneic mammary tumors and Matrigel
      implants suppressed angiogenesis as measured by endothelial cell
      immunohistochemistry and hemoglobin concentration. Taken together, these findings
      suggest a dual mechanism by which QRN suppresses endothelial cell proliferation,
      both acutely via inhibition of eNOS Ser 617 phosphorylation, and chronically via
      perturbation of mitotic microtubule polymerization. This novel mechanism of QRN
      in endothelial cells may in part explain its inhibitory action on angiogenesis
      and further discern a potential role of QRN as a chemopreventive agent.

PMID- 16614402
TI  - Zinc supplementation reduces iron absorption through age-dependent changes in
      small intestine iron transporter expression in suckling rat pups.
AB  - Zinc (Zn) supplementation negatively affects iron (Fe) absorption; however, the
      molecular mechanisms are not understood. We determined effects of Zn
      supplementation during mid- and late infancy on intestinal Fe transport
      mechanisms using a suckling rat model. Suckled rat pups were supplemented with 0
      (control), 300 (low), or 750 (high) microg Zn/d until weaning at postnatal day
      (PN) 20. At mid-(PN10) and late (PN20) infancy, tissue Fe distribution, Fe
      absorption, intestine DMT1, ferroportin-1 (FPN) and hephaestin expression, and
      localization and liver hepcidin expression were measured. During early infancy,
      DMT1 and FPN were localized intracellularly. Negative effects of Zn
      supplementation on Fe absorption were associated with increased small intestine
      Fe retention, decreased hephaestin, and increased FPN expression. During late
      infancy, both DMT1 and FPN were appropriately localized to the apical and
      basolateral membrane, respectively, and negative effects of Zn supplementation on
      Fe absorption were absent. Although FPN protein level was lower in Zn
      supplemented pups, hephaestin protein level was increased, which may have
      facilitated enhanced Fe efflux. These results indicate that Zn supplementation
      reduced Fe absorption during early infancy as a consequence of increased
      intestinal Fe retention due to reduced hephaestin levels. These effects were age
      dependent, further demonstrating that Fe transport regulation is not fully
      developed until weaning, which may have important implications regarding the
      safety and efficacy of Zn supplementation programs for infants.

PMID- 16614403
TI  - Chlorogenic acid is absorbed in its intact form in the stomach of rats.
AB  - The bioavailability of chlorogenic acid, a major polyphenol of the human diet
      that is particularly abundant in coffee and various fruits, was explored in rats.
      To identify the form under which it is absorbed through the gut mucosa and the
      site of absorption along the gastrointestinal tract, rats were fed a diet
      supplemented with chlorogenic acid (0.25%, wt:wt). Chlorogenic acid and its
      metabolites were estimated in the stomach, small intestine and cecal contents as
      well as in bladder urine and plasma by HPLC with coulometric detection at several
      time points (1.5, 3, 4.5, and 7 h) after the beginning of the meal. Minor
      hydrolysis of chlorogenic acid (<1%) occurred in the stomach and small intestine
      contents, whereas 15-32% of ingested chlorogenic acid was hydrolyzed into caffeic
      acid in the cecum. Chlorogenic acid and caffeic acid appeared early (at 1.5 h) in
      plasma and urine, suggesting an absorption of chlorogenic acid into the upper
      part of the gastrointestinal tract. Gastric absorption of chlorogenic acid was
      further examined by infusing chlorogenic acid in the ligated stomach of food
      deprived rats. After 30 min of infusion, intact chlorogenic acid was found in the
      gastric vein and aorta. No other metabolites could be detected by HPLC
      electrospray ionization-MS-MS. These results show for the first time that
      chlorogenic acid is quickly absorbed in the rat stomach in its intact form.

PMID- 16614404
TI  - Inulin alters the intestinal microbiota and short-chain fatty acid concentrations
      in growing pigs regardless of their basal diet.
AB  - Inulin stimulates intestinal bifidobacteria in humans and rodents but its effect
      in pigs is inconsistent. We assessed the effect of inulin on the intestinal
      microbiota by fluorescent in situ hybridization in growing pigs (age 9-12 wk).
      Pigs (n = 64) were assigned to 2 types of basal diets [wheat and barley (WB) or
      corn and wheat gluten (CG)] with or without 3% inulin (WBI or CGI) for 3 and 6 wk
      (n = 8/group) to test whether naturally occurring dietary fibers influence the
      inulin effect. Intestinal organic acids, pH values, and residual inulin were
      determined. The composition of the microbiota was highly individual. The duration
      of feeding did not affect any of the variables tested; therefore, data for the 2
      periods were pooled. Bifidobacteria were detected in less than half of the pigs.
      Inulin did not stimulate lactobacilli and bifidobacteria numbers irrespective of
      the basal diet, although 20-50% of inulin was degraded in the jejunum. The number
      of pigs with colonic bifidobacteria was higher in those fed diets containing
      inulin (40 vs. 13%; P < 0.05). Total colonic short-chain fatty acid (SCFA)
      concentrations were lower in both inulin-fed groups due to reduced acetate (P <
      0.05). Proportions of colonic butyrate were higher in pigs fed inulin
      supplemented diets (P < 0.05). Colonic pH tended to be lower in the WB groups
      (WB; 6.6 +/- 0.6), and was higher due to inulin (CGI, 7.1 +/- 0.1; P < 0.05). In
      conclusion, inulin affected intestinal SCFA and the number of pigs harboring
      bifidobacteria; this effect was independent of the basal diet.

PMID- 16614405
TI  - Anthropometrics provide a better estimate of urinary organic acid anion excretion
      than a dietary mineral intake-based estimate in children, adolescents, and young
      adults.
AB  - The role of elevated net endogenous acid production (NEAP) in the causation of
      osteoporosis, muscle wasting, and kidney stones is currently under discussion.
      The aim of this study was to examine whether urinary organic acid anion
      excretion, a major component of NEAP, is predicted primarily by anthropometric-
      (OA(anthro)) or diet- (OA(diet)) based estimates. Dietary intakes, anthropometric
      data, and 24-h urinary excretion rates of organic acids (24h-OA(urine)) were
      determined cross sectionally in healthy children (6-7 y; n = 217), adolescents
      (13-14 y; n = 91), and young adults (18-22 y; n = 82). OA(anthro) was computed
      from body surface area and OA(diet) calculated using a published algorithm based
      on dietary intakes of mineral anions and cations. There was a significant
      increase (P < 0.0001) in 24h-OA(urine) across the age groups that was no longer
      discernible after correction for body surface area. In almost all sex-stratified
      subsamples, OA(anthro) had a higher correlation with 24h-OA(urine) than OA(diet).
      Multiple regression analyses, using energy-corrected diet variables, revealed
      that OA(anthro) was consistently the primary predictor of 24h-OA(urine) (R(2)
      varying from 0.15 to 0.39) and dietary fat and protein were sporadic predictors.
      In accordance with the observed age independency of 24h-OA(urine) after body
      surface area correction, our findings indicate that OA(anthro) is a better
      estimate of 24h-OA(urine) in healthy children, adolescents, and young adults than
      OA(diet). This further confirms that the (principally diet-dependent) NEAP
      comprises a component, i.e., organic acid anions, that is reasonably predictable
      by anthropometrics. Consequently, the other component, i.e., the potential renal
      acid load, appears to be the primary parameter that characterizes the diet
      induced acid load.

PMID- 16614406
TI  - The conversion efficiency of trans-11 and trans-12 18:1 by Delta9-desaturation
      differs in rats.
AB  - The present study evaluated and compared the efficiency of the conversion of t11
      18:1 and t12 18:1 to their corresponding dienoic acids (c9,tn 18:2) and assessed
      whether differences due to gender existed in several tissues of rats. Three
      groups of 4-wk-old male and female rats were fed for 3 wk a diet supplemented
      with 0, 0.5, or 1% of a trans-octadecenoic acid isomer mixture (tOIM) containing
      t11 18:1 and t12 18:1 in equal proportion. t11 18:1 and t12 18:1 were
      incorporated in a tissue-specific manner, and the accrual was significant with
      increased dietary intake of these trans fatty acid (tFA) isomers. The t12 18:1
      isomer was more readily incorporated into the rat tissues than the t11 18:1
      isomer. From t11 and t12 18:1, the respective desaturase products, c9,t11 18:2
      and c9,t12 18:2, were formed. The calculated conversion rates varied greatly
      among the tissues of the rats but they were consistently lower for t12 18:1 than
      for t11 18:1, suggesting that t12 18:1 is a poorer substrate than t11 18:1 for
      Delta9-desaturase. For both fatty acids investigated, the calculated conversion
      rates in decreasing order of conversion efficiency were: testes = kidneys >
      adipose tissue > ovaries > muscle > liver > heart. Overall, there were distinct
      differences in the conversion of t11 18:1 and t12 18:1, indicating that these 2
      fatty acids are metabolized differently despite their structural similarities.
      Such metabolic differences in tFA accumulation and metabolism may have potential
      implication in assessing the safety of these tFA isomers because there is a
      positive correlation between the intake of tFA and the incidence of various
      diseases.

PMID- 16614407
TI  - Metabolic phenotype of isoflavones differ among female rats, pigs, monkeys, and
      women.
AB  - Various physiologic effects of soy food consumption have been attributed to the
      estrogenic actions of isoflavones. The order of estrogen receptor binding potency
      of soy-derived isoflavone aglycones is equol > genistein > daidzein, and their
      conjugates are less potent. Because the metabolic profile may be an important
      determinant of bioactivity after soy intake, we studied the serum and urine
      isoflavone concentrations in 3 animal models and compared them with isoflavone
      profiles in women. Female Sprague-Dawley rats, Hampshire/Duroc Cross pigs,
      cynomolgus monkeys, and women were fed diets containing soy protein isolate.
      Isoflavones and their metabolites were measured by LC-MS or electrochemical
      detection. Equol represented approximately 77 and 52% (molar ratio) of summed
      serum isoflavones (isoflavones plus metabolites) in rats and cynomolgus monkeys,
      respectively. Equol was undetectable in pig serum and human plasma, but daidzein
      and genistein contributed >88% of summed circulating isoflavones. Monkey and rat
      urine contained high levels of aglycones (>85% and >32%, respectively), whereas
      pigs and women excreted isoflavone mainly in the form of glucuronides (>80%),
      with <10% as aglycones. Isoflavones in human plasma were predominantly
      glucuronides (75%) with 24% as sulfates and <1% as aglycones; in monkey serum,
      however, 64% of isoflavones were sulfates, 30% glucuronides, and 6% aglycones.
      Equol was also a major serum metabolite of 6-mo-old rhesus monkeys (80% of summed
      isoflavones). Thus, there were significant interspecies differences in isoflavone
      metabolism, and the overall metabolic profile of pigs was closer to that of women
      than that of rats or monkeys.

PMID- 16614408
TI  - Dietary (n-3) fatty acids reduce plasma F2-isoprostanes but not prostaglandin
      F2alpha in healthy humans.
AB  - (n-3) Fatty acids are unsaturated and are therefore easily subject to
      oxidization; however, they have several beneficial health effects, which include
      protection against cardiovascular diseases. The aim of this study was to
      investigate whether (n-3) fatty acids, with a controlled fat quality in the
      background diet, affect nonenzymatic and enzymatic lipid peroxidation and
      antioxidant status in humans. A total of 162 men and women in a multicenter study
      (The KANWU study) were randomly assigned to a diet containing a high proportion
      of saturated fatty acids or monounsaturated fatty acids (MUFA) for 3 mo. Within
      each diet group, there was a second random assignment to supplementation with
      fish-oil capsules [3.6 g (n-3) fatty acids/d] or placebo. Biomarkers of
      nonenzymatic and enzymatic lipid peroxidation in vivo were determined by
      measuring 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) and prostaglandin
      F(2alpha) (PGF(2alpha)) concentrations in plasma at baseline and after 3 mo.
      Antioxidant status was determined by measuring plasma antioxidant capacity with
      an enhanced chemiluminescence assay. The plasma 8-iso-PGF(2alpha) concentration
      was significantly decreased after 3 mo of supplementation with (n-3) fatty acids
      (P = 0.015), whereas the PGF(2alpha) concentration was not affected. The
      antioxidant status was not affected by supplementation of (n-3) fatty acids, but
      was improved by the background diet with a high proportion of MUFA. We conclude
      that supplementation with (n-3) fatty acids decreases nonenzymatic free radical
      catalyzed isoprostane formation, but does not affect cyclooxygenase-mediated
      prostaglandin formation.

PMID- 16614409
TI  - A continuous dietary supply of free calcium formate negatively affects the
      parietal cell population and gastric RNA expression for H+/K+-ATPase in weaning
      pigs.
AB  - Baby formula acidification can be used to reduce diarrhea. Calcium formate is a
      dietary acidifier frequently used in animal weaning diets; it is also a source of
      available calcium. Gastric acidification reduces gastrin release and hydrochloric
      acid (HCl) secretion. To study the medium-term effects on fundic gastric mucosa,
      we fed weaning pigs control diets or diets supplemented with free or fat
      protected calcium formate. We evaluated the following: 1) the number of HCl
      secreting parietal cells, by immunohistochemistry using an antibody against
      H(+)/K(+)-ATPase; 2) the number of enteroendocrine cells immunohistochemically
      stained with chromogranin A (CGA), somatostatin, and histamine (HIS); and 3) the
      expression of the H(+)/K(+)-ATPase gene, by real-time RT-PCR in the oxyntic
      mucosa. Cells co-staining for CGA and HIS were defined as enterochromaffin-like
      (ECL) cells. Pigs fed calcium formate had fewer parietal cells and a lower
      expression of the H(+)/K(+)-ATPase gene than the controls (P < 0.05). This
      reduction did not occur in pigs fed fat-protected calcium formate. Somatostatin
      immune-reactive cells were also more numerous in pigs fed free calcium formate
      than in controls (P < 0.05). The number of ECL cells was not affected. Using
      covariance analysis, the number of parietal cells explained part of the
      differences in the expression of H(+)/K(+)-ATPase gene (positive correlation, r =
      0.385, P < 0.01), and excluded the statistical significance of the diet. In the
      future, the effects on the oxyntic mucosa should be checked when the diet
      supplemented with calcium formate is discontinued. Furthermore, a reduction in
      the number of parietal cells could impair the absorption of vitamin B-12 due to a
      reduced secretion of the intrinsic factor by these cells.

PMID- 16614410
TI  - Decreased hephaestin activity in the intestine of copper-deficient mice causes
      systemic iron deficiency.
AB  - Copper and iron metabolism intersect in mammals. Copper deficiency simultaneously
      leads to decreased iron levels in some tissues and iron deficiency anemia,
      whereas it results in iron overload in other tissues such as the intestine and
      liver. The copper requirement of the multicopper ferroxidases hephaestin and
      ceruloplasmin likely explains this link between copper and iron homeostasis in
      mammals. We investigated the effect of in vivo and in vitro copper deficiency on
      hephaestin (Heph) expression and activity. C57BL/6J mice were separated into 2
      groups on the day of parturition. One group was fed a copper-deficient diet and
      another was fed a control diet for 6 wk. Copper-deficient mice had significantly
      lower hephaestin and ceruloplasmin (approximately 50% of controls) ferroxidase
      activity. Liver hepcidin expression was significantly downregulated by copper
      deficiency (approximately 60% of controls), and enterocyte mRNA and protein
      levels of ferroportin1 were increased to 2.5 and 10 times, respectively, relative
      to controls, by copper deficiency, indicating a systemic iron deficiency in the
      copper-deficient mice. Interestingly, hephaestin protein levels were
      significantly decreased to approximately 40% of control, suggesting that
      decreased enterocyte copper content leads to decreased hephaestin synthesis
      and/or stability. We also examined the effect of copper deficiency on hephaestin
      in vitro in the HT29 cell line and found dramatically decreased hephaestin
      synthesis and activity. Both in vivo and in vitro studies indicate that copper is
      required for the proper processing and/or stability of hephaestin.

PMID- 16614411
TI  - Thiol/disulfide redox status is oxidized in plasma and small intestinal and
      colonic mucosa of rats with inadequate sulfur amino acid intake.
AB  - Low molecular weight thiol/disulfide redox pools are dependent upon extracellular
      cysteine (Cys) availability. We determined whether dietary sulfur amino acid
      (SAA) deficiency induces oxidative stress in vivo, as determined by redox state
      of major thiol/disulfide couples in plasma [Cys/cystine (CySS)] and intestinal
      mucosa [glutathione (GSH)/glutathione disulfide (GSSG)]. Rats were fed
      isocaloric, isonitrogenous semipurified diets: either SAA-adequate (control), SAA
      deficient, or SAA-supplemented, pair-fed to intake of the SAA-deficient group.
      Reference rats consumed standard rat food ad libitum. After 7 d, plasma and gut
      mucosal samples were analyzed for Cys, CySS, GSH and GSSG, and the redox
      potentials of Cys/CySS and GSH/GSSG were determined. Mean daily food intake in
      the pair-fed rats was similar (approximately one-half of reference-rat intake).
      Body weight decreased in all pair-fed groups, but rats fed the SAA-deficient diet
      lost significantly more body weight. Dietary SAA deficiency decreased GSH
      concentrations in both plasma and gut mucosa, increased plasma GSSG, and oxidized
      plasma and gut mucosal GSH/GSSG redox and plasma Cys/CySS redox. SAA
      supplementation resulted in a more reducing plasma Cys/CySS redox potential.
      Reference rats exhibited similar tissue and plasma GSH/GSSG redox as rats that
      ate semipurified SAA-adequate rat food, which provided similar net SAA intake.
      Our in vivo data show that inadequate dietary SAA intake oxidizes the
      thiol/disulfide redox status in rat-gut mucosa and plasma. Such oxidation of
      redox pools is associated with oxidative stress and the onset or progression of
      several pathological conditions. Thus, dietary SAA deficiency could contribute to
      the progression of disease by causing an oxidation of these components.

PMID- 16614413
TI  - A high-protein, high-fat, carbohydrate-free diet reduces energy intake, hepatic
      lipogenesis, and adiposity in rats.
AB  - The aim of this work was to determine the effects in rats of ingesting 1 of 3
      diets with normal or high protein concentrations and various carbohydrate:lipid
      ratios on weight gain, body composition, and the development and metabolism of
      white adipose tissue (WAT). For this purpose, male Wistar rats were fed for 20 or
      42 d a high-carbohydrate, low-fat, normal-protein diet (76, 10, and 14% of energy
      as carbohydrate, lipid, and protein, respectively, carbohydrate:lipid ratio (C/L)
      = 7.6), a normal-carbohydrate, low-fat, high-protein diet (35, 10, and 55% of
      energy as carbohydrate, lipid, and protein respectively, C:L = 3.5), or a
      carbohydrate-free, high-fat, high-protein diet (45 and 55% of energy as fat and
      protein, respectively, C:L = 0). Growth, food intake, body composition, WAT
      cellularity, and several markers of lipogenesis including fatty acid synthase and
      lipoprotein lipase activities were measured in adipose tissue and liver. Lowering
      the C:L ratio reduced the development of WAT, weight gain, body fat mass, and
      adipocyte size, and in rats fed the carbohydrate-free diet (C:L = 0), the total
      number of adipocytes in subcutaneous WAT. These reductions in adipose tissue
      development with decreases in the C:L ratio of the diet seemed to be due
      primarily to reduced hepatic lipogenesis.

PMID- 16614412
TI  - Skeletal muscle protein anabolic response to increased energy and insulin is
      preserved in poorly controlled type 2 diabetes.
AB  - Type 2 diabetes (T2DM) subjects failing diet treatment are characterized by
      hyperinsulinemia and insulin resistance leading to fasting and postprandial
      hyperglycemia and hyperlipidemia. Energy is essential for allowing the process of
      protein synthesis to proceed. Additionally, insulin can stimulate protein
      synthesis in human muscle. The aims of this study were to determine if poorly
      controlled T2DM affects postabsorptive muscle protein anabolism, and if the
      muscle anabolic response to hyperinsulinemia with high energy availability is
      maintained. Control (n = 6) and T2DM subjects (n = 6) were studied in the
      postabsorptive state and during an isoenergetic high nutritional energy clamp
      (relative to postabsorptive state). Muscle protein synthesis and breakdown (nmol
      . min(-1) . 100 g leg muscle(-1)) were assessed using stable isotope methodology,
      femoral arterio-venous sampling, muscle biopsies, and a three-pool model to
      calculate protein turnover. Postabsorptive phenylalanine net balance and whole
      body rate of appearance (Ra) were not different between groups; however, basal
      muscle protein breakdown was higher in T2DM (94 +/- 9) than in controls (58 +/-
      12) (P < 0.05) and muscle protein synthesis tended (P = 0.07) to be elevated in
      T2DM (66 +/- 14) compared with controls (39 +/- 6). During the clamp, net balance
      increased, whole body Ra and muscle protein breakdown decreased (P < 0.05), and
      muscle protein synthesis tended to decrease (P = 0.08) to a similar extent in
      both groups. We conclude that postabsorptive muscle protein turnover is elevated
      in poorly controlled T2DM, however, there is no excessive loss of muscle protein
      because net balance is not different from controls. Moreover, the anabolic
      response to increased insulin and energy availability is maintained in T2DM.

PMID- 16614414
TI  - Intestinal protein supply alters amino acid, but not glucose, metabolism by the
      sheep gastrointestinal tract.
AB  - This study was intended to establish the extent which amino acids (AAs) and
      glucose are net metabolized by the gastrointestinal tract (GIT) of ruminant sheep
      when intestinal protein supply is varied. Wether sheep (n = 4, 33 +/- 2.0 kg)
      were fitted with catheters for measurement of net absorption by the mesenteric
      (MDV) and portal-drained (PDV) viscera and a catheter inserted into the duodenum
      for casein infusions. Sheep received a fixed amount of a basal diet that provided
      adequate metabolizable energy (10.9 MJ/d) but inadequate metabolizable protein
      (75 g/d) to support 300-g gain per day. Four levels of casein infusion [0
      (water), 35, 70, and 105 g/d], each infused for 5.5 d, were assigned to sheep
      according to a 4 x 4 Latin square design. [methyl-(2)H(3)]leucine was infused (8
      h) into the duodenum while [1-(13)C]leucine plus [6-(2)H(2)]glucose were infused
      (8 h) into a jugular vein. With the exception of glutamate and glutamine, net
      absorption of AAs increased linearly (P < 0.05, R(2) = 0.46-1.79 for MDV; P <
      0.05, R(2) = 0.6-1.58 for PDV) with casein infusion rate. Net absorption by the
      PDV accounted for <100% of the additional supplies of leucine, valine, and
      isoleucine (0.6-0.66, P < 0.05) from casein infusion, whereas net absorption by
      the MDV accounted for 100% of the additional essential AA supply. Glucose
      absorption (negative) and utilization of arterial glucose supply by the GIT
      remained unchanged. There was a positive linear (P < 0.05) relation between
      transfer of plasma urea to the GIT and arterial urea concentration (MDV, P <
      0.05, r = 0.90; PDV, P < 0.05, r = 0.93). The ruminant GIT appears to metabolize
      increasing amounts of the branched-chain AAs and certain nonessential AAs when
      the intestinal supply of protein is increased.

PMID- 16614415
TI  - Sesame ingestion affects sex hormones, antioxidant status, and blood lipids in
      postmenopausal women.
AB  - Sesame ingestion has been shown to improve blood lipids in humans and
      antioxidative ability in animals. Sesamin, a sesame lignan, was recently reported
      to be converted by intestinal microflora to enterolactone, a compound with
      estrogenic activity and also an enterometabolite of flaxseed lignans, which are
      known to be phytoestrogens. Whether sesame can be a source of phytoestrogens is
      unknown. This study was designed to investigate the effect of sesame ingestion on
      blood sex hormones, lipids, tocopherol, and ex vivo LDL oxidation in
      postmenopausal women. Twenty-six healthy subjects attended, and 24 completed,
      this randomized, placebo-controlled, crossover study. Half of them consumed 50 g
      sesame seed powder daily for 5 wk, followed by a 3-wk washout period, then a 5-wk
      50-g rice powder placebo period. The other half received the 2 supplements in
      reverse order. After sesame treatment, plasma total cholesterol (TC), LDL-C, the
      ratio of LDL-C to HDL-C, thiobarbituric acid reactive substances in oxidized LDL,
      and serum dehydroepiandrosterone sulfate decreased significantly by 5, 10, 6, 23,
      and 18%, respectively. The ratio of alpha- and gamma-tocopherol to TC increased
      significantly by 18 and 73%, respectively. All of these variables differed
      significantly between the 2 treatments. Serum sex hormone-binding globulin and
      urinary 2-hydroxyestrone (n = 8) increased significantly by 15 and 72%,
      respectively, after sesame treatment, and these concentrations tended to differ
      (P = 0.065 and P = 0.090, respectively) from those after the placebo treatment.
      These results suggest that sesame ingestion benefits postmenopausal women by
      improving blood lipids, antioxidant status, and possibly sex hormone status.

PMID- 16614416
TI  - The glucose intolerance induced by caffeinated coffee ingestion is less
      pronounced than that due to alkaloid caffeine in men.
AB  - Although acute alkaloid caffeine (CAF) ingestion results in an impaired glucose
      tolerance, chronic coffee (RCOF) ingestion decreases the risk of developing type
      2 diabetes. This study examines the hypothesis that CAF ingestion impairs glucose
      tolerance to a greater extent than RCOF and that the ingestion of decaffeinated
      coffee (DECAF) results in a positive effect. Eleven healthy males underwent 4
      double-blinded randomized trials. Each trial included the ingestion of either: 1)
      CAF in capsule form (4.45 mg/kg body weight), 2) RCOF (4.45 mg/kg body weight
      caffeine), 3) dextrose (placebo, PL) in capsule form, or 4) DECAF (equal in
      volume to the RCOF trial), followed 1-h later by a 2-h oral glucose tolerance
      test. Blood samples were collected at baseline (-30), 0 (time of treatment
      ingestion), 60 (initiation of oral glucose tolerance test), 75, 90, 120, 150, and
      180 min. Area under the curve for glucose and insulin were higher (P < or = 0.05)
      following CAF than both PL and DECAF and, although a similar trend (P = 0.07) was
      observed following RCOF compared with DECAF, the effect was less pronounced.
      Interestingly, DECAF resulted in a 50% lower glucose response (P < or = 0.05)
      than PL, suggesting that the effects of PL and DECAF on glucose tolerance are not
      the same. These findings suggest that the effects of CAF and RCOF are not
      identical and may provide a partial explanation as to why acute CAF ingestion
      impairs glucose tolerance while chronic RCOF ingestion protects against type 2
      diabetes.

PMID- 16614417
TI  - Girls' calcium intake is associated with bone mineral content during middle
      childhood.
AB  - We examined longitudinally the association between calcium intake and total body
      bone mineral content (TBBMC) in 151 non-Hispanic white girls. Intakes of dairy,
      energy, and calcium were assessed using three 24-h dietary recalls in girls at
      ages 5, 7, 9, and 11 y. We assessed their total-body bone mineral content with
      dual-energy X-ray absorptiometry at ages 9 and 11 y. Dairy foods comprised the
      major contributor (70%) to calcium intake over the 6-y period; 28% of calcium
      came from other foods, and 2% from supplements. By age 9 and 11 y, the majority
      of girls did not meet calcium recommendations. Higher calcium intake at ages 7
      and 9 y was associated with higher TBBMC at age 11 y. Calcium intake at age 9 y
      was also positively associated with TBBMC gained from age 9 to 11 y. Calcium
      intake at age 11 y was not correlated with TBBMC at the same age. Relations
      between calcium intake and TBBMC did not differ for total calcium and for calcium
      from dairy sources, likely reflecting the fact that dairy products were the major
      source of calcium in this sample. Results from the present study provide new
      longitudinal evidence that calcium intake, especially calcium from dairy foods,
      can have a favorable effect on girls' TBBMC during middle childhood.

PMID- 16614418
TI  - Combined lycopene and vitamin E treatment suppresses the growth of PC-346C human
      prostate cancer cells in nude mice.
AB  - Epidemiologic studies have repeatedly associated a high intake of lycopene and
      vitamin E with reduced prostate cancer risk. The present study examined the
      ability of the 2 compounds to reduce tumor growth and prostate-specific antigen
      (PSA) plasma levels in the PC-346C orthotopic mouse model of human prostate
      cancer. Three days after intraprostatic tumor injection, NMRI nu/nu mice were
      administered a daily oral dose of synthetic lycopene [5 or 50 mg/kg body weight
      (BW)], vitamin E in the form of alpha-tocopheryl acetate (5 or 50 mg/kg BW), a
      mixture of lycopene and vitamin E (5 mg/kg BW each), or vehicle. Intraprostatic
      tumor volume and plasma PSA concentrations were measured at regular intervals.
      Mice were killed when the tumor load exceeded 1000 mm(3) or on d 95 when the
      study was terminated. Prostate and liver were analyzed by HPLC for lycopene
      isomers and alpha- and gamma, delta-tocopherol concentrations. None of the single
      treatments significantly reduced tumor volume. In contrast, combined treatment
      with lycopene and vitamin E, at 5 mg/kg BW each, suppressed orthotopic growth of
      PC-346C prostate tumors by 73% at d 42 (P < 0.05) and increased median survival
      time by 40% from 47 to 66 d (P = 0.02). The PSA index (PSA:tumor volume ratio)
      did not differ between experimental groups, indicating that PSA levels were not
      selectively affected. Lycopene was detected only in mice supplemented with
      lycopene. As in humans, most tissue lycopene was in the cis-isomer conformation,
      whereas 77% trans-lycopene was used in the dosing material. Liver alpha
      tocopherol concentrations were increased in mice supplemented with both 50 mg/kg
      (226%, P < 0.05) and 5 mg/kg vitamin E (41%, P < 0.05), whereas prostate alpha
      tocopherol concentrations were increased only by the higher dose (83%, P < 0.05).
      Our data provide evidence that lycopene combined with vitamin E may inhibit the
      growth of prostate cancer and that PSA can serve as a biomarker of tumor response
      for this treatment regimen.

PMID- 16614419
TI  - Co-ingestion of a protein hydrolysate with or without additional leucine
      effectively reduces postprandial blood glucose excursions in Type 2 diabetic men.
AB  - This study examined postprandial plasma insulin and glucose responses after co
      ingestion of an insulinotropic protein (Pro) hydrolysate with and without
      additional free leucine with a single bolus of carbohydrate (Cho). Male patients
      with long-standing Type 2 diabetes (n = 10) and healthy controls (n = 10)
      participated in 3 trials in which plasma glucose, insulin, and amino acid
      responses were determined after the ingestion of beverages of different
      composition (Cho: 0.7 g/kg carbohydrate, Cho+Pro: 0.7 g/kg carbohydrate with 0.3
      g/kg protein hydrolysate, or Cho+Pro+Leu: 0.7 g/kg carbohydrate, 0.3 g/kg protein
      hydrolysate and 0.1 g/kg free leucine). Plasma insulin responses [expressed as
      area under the curve (AUC)] were 141 and 204% greater in patients with Type 2
      diabetes and 66 and 221% greater in the controls in the Cho+Pro and Cho+Pro+Leu
      trials, respectively, compared with those in the Cho trial (P < 0.05). The
      concomitant plasma glucose responses were 15 and 12% lower in the patients with
      Type 2 diabetes and 92 and 97% lower in the control group in the Cho+Pro and
      Cho+Pro+Leu trials, respectively, compared with those in the Cho trial (P <
      0.05). Plasma leucine concentrations correlated with the insulin response in all
      subjects (r = 0.43, P < 0.001). We conclude that co-ingestion of a protein
      hydrolysate with or without additional free leucine strongly augments the insulin
      response after ingestion of a single bolus of carbohydrate, thereby significantly
      reducing postprandial blood glucose excursions in patients with long-standing
      Type 2 diabetes.

PMID- 16614420
TI  - Neoplastic transformation of BALB/3T3 cells and cell cycle of HL-60 cells are
      inhibited by mango (Mangifera indica L.) juice and mango juice extracts.
AB  - The mango, Mangifera indica L., is a fruit with high levels of phytochemicals,
      suggesting that it might have chemopreventative properties. In this study, whole
      mango juice and juice extracts were screened for antioxidant and anticancer
      activity. Antioxidant activity of the mango juice and juice extracts was measured
      by 3 standard in vitro methods. The results of the 3 methods were in general
      agreement, although different radicals were measured in each. Anticancer activity
      was measured by examining the effect on cell cycle kinetics and the ability to
      inhibit chemically induced neoplastic transformation of mammalian cell lines.
      Incubation of HL-60 cells with whole mango juice and mango juice fractions
      resulted in an inhibition of the cell cycle in the G(0)/G(1) phase. A fraction of
      the eluted mango juice with low peroxyl radical scavenging ability was most
      effective in arresting cells in the G(0)/G(1) phase. Whole mango juice was
      effective in reducing the number of transformed foci in the neoplastic
      transformation assay in a dose-dependent manner. These techniques provide
      valuable screening tools for health benefits derived from mango phytochemicals.

PMID- 16614421
TI  - The natural concentration of the conjugated linoleic acid, cis-9,trans-11, in
      milk fat has antiatherogenic effects in hyperlipidemic hamsters.
AB  - Milk fat is usually considered to be proatherogenic, although its fatty acid
      composition can vary, due mainly to farming conditions. No study has evaluated
      whether such variation can modify the atherogenic properties of dairy fat. Aortic
      lipid deposition and related risk factors were examined in Syrian hamsters fed
      diets for 12 wk containing 200 g/kg of 2 commercial milk fats [high content of
      saturated fatty acids (HSF) and low content of saturated fatty acids (LSF)]
      contrasting, respectively, in total saturated fatty acids (72 vs. 67 g/100 g),
      18:1, trans (4.24 vs. 7.26 g/100g), and conjugated linoleic acid (mainly cis
      9,trans-11 or rumenic acid; 0.39 vs. 2.59 g/100 g). Hamsters fed the LSF-diet had
      25% less aortic cholesteryl-ester deposition than those fed the HSF-diet; this
      was accompanied by an improved plasma cholesterol profile (lower LDL cholesterol
      and LDL:HDL cholesterol ratio), a lower local inflammatory status (aortic gene
      expression of cyclooxygenase-2), and lower aortic gene expression of vascular
      cell adhesion molecule-1 (all P < 0.05). Supplementation of the LSF-diet with
      rumenic acid (up to 9 g/kg) amplified the antiatherogenic effect of the original
      LSF-diet compared with the HSF-diet, i.e., less aortic cholesterol loading,
      increased reverse cholesterol transport potential (higher plasma HDL cholesterol
      concentration and ATP-binding cassette, subfamily A, transporter 1 gene
      expression in aorta), and decreased LDL-peroxidability index and gene expression
      of proinflammatory IL-1beta in the aorta (all P < 0.05). In conclusion, our
      results suggest that the atherogenic potential of milk fat can be greatly reduced
      in products with a naturally high abundance of rumenic acid, and argue for
      increasing this fatty acid in milk.

PMID- 16614422
TI  - Both selenoproteins and low molecular weight selenocompounds reduce colon cancer
      risk in mice with genetically impaired selenoprotein expression.
AB  - Selenium has cancer protective effects in a variety of experimental systems.
      Currently, it is not known whether selenoproteins or low molecular weight
      selenocompounds are responsible for this activity. To evaluate the contribution
      of selenoproteins to the cancer protective effects of selenium, we used
      transgenic mice that carry a mutant selenocysteine transfer RNA gene, which
      causes reduced selenoprotein synthesis. Selenium homeostasis was characterized in
      liver and colon of wild-type and transgenic mice fed selenium-deficient diets
      supplemented with 0, 0.1, or 2.0 microg selenium (as selenite)/g diet. (75)Se
      labeling, Western blot analysis, and enzymatic activities revealed that
      transgenic mice have reduced (P < 0.05) liver and colon glutathione peroxidase
      expression, but conserved thioredoxin reductase expression compared with wild
      type mice, regardless of selenium status. Transgenic mice had more (P < 0.05)
      selenium in the nonprotein fraction of the liver and colon than wild-type mice,
      indicating a greater amount of low molecular weight selenocompounds. Compared
      with wild-type mice, transgenic mice had more (P < 0.05) azoxymethane-induced
      aberrant crypt formation (a preneoplastic lesion for colon cancer). Supplemental
      selenium decreased (P < 0.05) the number of aberrant crypts and aberrant crypt
      foci in both wild-type and transgenic mice. These results provide evidence that a
      lack of selenoprotein activity increases colon cancer susceptibility.
      Furthermore, low molecular weight selenocompounds reduced preneoplastic lesions
      independent of the selenoprotein genotype. These results are, to our knowledge,
      the first to provide evidence that both selenoproteins and low molecular weight
      selenocompounds are important for the cancer-protective effects of selenium.

PMID- 16614423
TI  - Dietary energy density is associated with selected predictors of obesity in U.S.
      Children.
AB  - Increasing rates of childhood overweight have been linked to the rising energy
      density of the diet. We sought to provide temporal profiles of dietary energy
      density (DED) in a nationally representative sample of U.S. children and
      adolescents < or = 19 y old and to describe associations between DED and
      predictors of overweight. We used a subset of data from the 1994-1996, 1998
      Continuing Survey of Food Intake for Individuals (CSFII) and a multivariate
      regression model to determine independent associations between DED and
      socioeconomic and demographic variables after controlling for covariates. In this
      cross-sectional data set, DED was positively associated with total energy intakes
      and varied with both age and gender. DED increased from birth, peaked at 7-8 y of
      age, and then declined. Boys consumed more energy-dense diets than girls. Among
      children < or = 4 y old, higher DED was associated in the regression model with
      lower household incomes and with enrollment in the food stamp program. Among
      adolescents 12-19 y old, higher DED was associated with being African-American.
      In contrast, lower DED among children < or = 11 y old was associated with being
      Asian or Hispanic and with total daily consumption of fluid milk. The quality of
      the diet for young children, as indexed by high DED, may be adversely affected by
      limited household economic resources. Although food insecurity and WIC enrollment
      were not associated with DED in this study sample, milk consumption in children <
      or = 4 y old was associated with lower DED.

PMID- 16614424
TI  - Intake of fermented soybeans, natto, is associated with reduced bone loss in
      postmenopausal women: Japanese Population-Based Osteoporosis (JPOS) Study.
AB  - Japanese fermented soybeans (natto in Japanese), which contain a large amount of
      menaquinone-7, may help prevent the development of osteoporosis. We assessed the
      possibility of an association between habitual natto intake and bone mineral
      density (BMD) and BMD change over time in healthy Japanese women who participated
      in a large representative cohort study (Japanese Population-based Osteoporosis
      Study: JPOS study). The BMD was measured at the spine, hip, and forearm in 944
      women (20-79 y old) at baseline and at a follow-up conducted 3 y later. Dietary
      natto intake was assessed by a FFQ on both occasions. Additional covariates
      including age, height, weight, lifestyle factors, dietary calcium intake, and the
      intake of other soybean products, were also measured. The total hip BMD at
      baseline increased (P for trend = 0.0034) with increasing habitual natto intake
      in the postmenopausal women, although this was not the case at other skeletal
      sites. There were significant positive associations between natto intake and the
      rates of changes in BMD at the femoral neck (P < 0.0001) and at the distal third
      of the radius (P = 0.0002) in the postmenopausal women. The association in the
      femoral neck persisted even after adjusting for covariates. No significant
      association was observed between the intake of tofu or other soybean products and
      the rate of BMD change in the postmenopausal women. Natto intake may help prevent
      postmenopausal bone loss through the effects of menaquinone 7 or bioavailable
      isoflavones, which are more abundant in natto than in other soybean products.

PMID- 16614425
TI  - Vitamin intakes from supplements and fortified food in German children and
      adolescents: results from the DONALD study.
AB  - Frequent consumption of supplements is a common behavior in adults, as well as
      children and adolescents. We report on vitamin intake from consuming supplements,
      taking into account the vitamin intake from fortified and usual foods. A total of
      5990 3-d weighed dietary records from 931 German subjects (452 males, 479
      females, 2-18 y of age) between 1986 and 2003 from the Dortmund Nutritional and
      Anthropometric Longitudinally Designed (DONALD) Study were evaluated. We
      identified 133 different vitamin-containing supplements in 451 records (7.5%).
      Slightly more males (8.0%) than females (7.1%) consumed supplements, with highest
      frequencies found between ages 15 and 18 y. For the majority (10 of 13) of
      vitamins (vitamin A, vitamin E, vitamin K, thiamin, riboflavin, vitamin B-6,
      vitamin B-12, niacin, biotin, and vitamin C), intake from usual and fortified
      food already reached or exceeded 80% of the recommended dietary allowances in all
      age groups. In the case of folate and pantothenic acid, intake from supplements
      was necessary to achieve at least 80% of recommended dietary allowances for half
      of the age groups, especially in females. Supplements with vitamin D considerably
      helped increase vitamin intake but failed to achieve 80% of references in almost
      all age groups. Intakes of vitamin A and folic acid exceeded the tolerable upper
      level most frequently in many age groups and were most pronounced in up to 32%
      and 13% of children aged 2-3 y. Intake of vitamin D, vitamin E, and vitamin C
      exceeded the tolerable upper level in single age groups only (<7% of subjects).
      For the other vitamins, no exceeded limits were identified. The ubiquitous
      availability of supplements might indicate that even healthy children and
      adolescents profit by taking them. However, it is difficult to evaluate whether
      consumers receive more benefits or risks from the unrestricted consumption of
      supplements as they are marketed today.

PMID- 16614426
TI  - Urinary potassium is as reliable as urinary nitrogen for use as a recovery
      biomarker in dietary studies of free living individuals.
AB  - Twenty-four-hour urinary nitrogen (UN) is commonly used to validate dietary
      assessment methods. Potassium is more widespread in food than nitrogen, but the
      role of 24-h urinary potassium (UK) as a biomarker has been less studied and
      characterized. To investigate the performance of UK as a recovery biomarker
      compared with UN in subjects consuming their normal diet, 7 males and 6 females
      consumed known amounts of food based on their habitual varying diet (assessed
      beforehand from 4 consecutive 7-d food diaries) for 30 d in a metabolic suite.
      All daily urine samples and dietary duplicates were collected, and N and K were
      measured. Stool K was determined in 5-d pooled samples. Thirty-day mean analyzed
      K intake was 121.3 +/- 25.1 (mean +/- SD) mmol/d. Overall, 77 +/- 6.7% of K in
      the diet was excreted in urine and 18 +/- 5% in stool. Dietary K was correlated
      with UK (r = 0.89; P < 0.001). UN was 77.7 +/- 6.6% of N intake and was
      correlated with N in the diet (r = 0.87; P < 0.001). When 16 d of intake and 8 d
      of urine-collection measurements were randomly selected from the 30-d
      measurements, correlations were significant for both K (r = 0.86; P < 0.001) and
      N (r = 0.92; P < 0.001). The high correlations between UK and K in the diet show
      that UK is a reliable recovery biomarker for use in studies of dietary
      measurement error. Factors for use of urinary N as a recovery biomarker are also
      confirmed.

PMID- 16614427
TI  - The 2005 USDA Food Guide Pyramid is associated with more adequate nutrient
      intakes within energy constraints than the 1992 Pyramid.
AB  - The USDA issued the Food Guide Pyramid (FGP) to help Americans choose healthy
      diets. We examined whether adherence to the 1992 and 2005 FGP was associated with
      moderate energy and adequate nutrient intakes. We used data for 2138 men and 2213
      women > 18 y old, from the 2001-2002 U.S. National Health and Nutrition
      Examination Survey (NHANES). Quadratic programming was used to generate diets
      with minimal departure from intakes reported for the NHANES 2001-02. We examined
      the effect of the number of servings/d of Food Pyramid groups set at 1992 and at
      2005 FGP recommendations for 1600, 2200, and 2800 kcal (1 kcal = 4.184 kJ)
      levels. We calculated energy and nutrients provided by different FGP dietary
      patterns. Within current U.S. dietary practices, following the 1992 FGP without
      sodium restriction may provide 200 more kcal than recommended for each energy
      level. Although it can meet most of old nutrient recommendations (1989), it fails
      to meet the latest dietary reference intakes, especially for the 1600 kcal level.
      The 2005 FGP appears to provide less energy and more adequate nutrient intakes,
      with the exception of vitamin E and potassium for some groups. However, without
      discretionary energy restriction, Americans are at risk of having excessive
      energy intake even if they follow the 2005 FGP food serving recommendations. Our
      analysis suggests that following the 2005 FGP may be associated with lower energy
      and optimal nutrient intake. Careful restriction of discretionary calories
      appears necessary for appropriate energy intakes to be maintained.

PMID- 16614428
TI  - Prevalence of daidzein-metabolizing phenotypes differs between Caucasian and
      Korean American women and girls.
AB  - Interindividual differences in metabolism of the soy isoflavone, daidzein, to
      equol and O-desmethylangolensin (ODMA) by human gut bacteria, have been
      associated with altered risk of cancer and other chronic diseases, according to
      some studies. Differences have been reported in the prevalence of the equol
      producer phenotype among populations, with a higher prevalence in soy-consuming
      Asian populations than in Western populations. To date, prevalence of the
      daidzein-metabolizing phenotypes in Asians, compared with Caucasians, has not
      been evaluated in the context of a standardized phenotyping method. We assessed
      the prevalence of equol- and ODMA-producer phenotypes in 91 Korean American (KA)
      women and girls living in the Seattle, Washington area and compared this with
      previous similarly collected prevalence data in Caucasian American (CA) women and
      girls (n = 222). We also compared the dietary habits of the 2 groups.
      Isoflavonoid concentrations in first-void morning urines, collected after a 3-d
      soy challenge, were used to establish equol-, and ODMA-producer phenotypes (>44
      microg/L). The prevalence of the equol-producer phenotype was higher (51 vs. 36%;
      P = 0.015) and the ODMA-producer phenotype was lower (84 vs. 92%, P = 0.03) in KA
      than in CA women and girls. KAs consumed approximately 3 times more soy foods
      than the CAs, but no significant associations were found between the consumption
      of soy foods and equol-producer phenotype. Our findings support the reports that,
      compared with Western populations, Asian populations have a higher equol-producer
      prevalence. The additional observation that the prevalence of the ODMA-producer
      phenotype is lower in KAs suggests that daidzein-metabolizing patterns in general
      may differ between KAs and CAs.

PMID- 16614429
TI  - Dietary patterns and glucose tolerance abnormalities in Japanese men.
AB  - The Western dietary pattern appears to confer diabetes risk, but the role of
      dietary patterns in Asian populations remains unclear. We investigated the
      association between major dietary patterns and the glucose tolerance status of
      Japanese men. Abnormalities included impaired fasting glucose, impaired glucose
      tolerance, and type 2 diabetes. Subjects were 2106 Japanese men who were
      administered a 75-g oral glucose tolerance test at their preretirement health
      check-ups. Information about diet was obtained using a 74-item FFQ before the
      test. Three dietary patterns were generated by factor analysis: 1) a high-dairy,
      high-fruit and -vegetable, high-starch, low-alcohol pattern; 2) an animal food
      pattern; and 3) a Japanese pattern. We used logistic regression analysis to
      estimate odds ratios (OR) with adjustment for potential confounding variables. A
      significant inverse association was found for the high-dairy, high-fruit and 
      vegetable, high-starch, low-alcohol pattern (P for trend < 0.0001); the OR of
      having a glucose tolerance abnormality (impaired fasting glucose, impaired
      glucose tolerance, or type 2 diabetes) for the 2nd, 3rd, and 4th quartiles were
      0.80 (95% CI = 0.62-1.04), 0.71 (95% CI = 0.54-0.92), and 0.51 (95% CI = 0.38
      0.67), respectively, compared with the lowest quartile. The inverse association
      was consistent for each glucose tolerance abnormality as well as across subgroups
      stratified by risk factors for diabetes. The Japanese dietary pattern was
      positively associated with impaired glucose tolerance (P for trend = 0.048). A
      dietary pattern characterized by frequent consumption of dairy products and
      fruits and vegetables but low alcohol intake may be associated with a decreased
      risk of developing a glucose tolerance abnormality.

PMID- 16614430
TI  - Allowing for variations in multivitamin supplement composition improves nutrient
      intake estimates for epidemiologic studies.
AB  - Collecting detailed data on dietary supplement use is time-consuming for study
      participants and investigators, and this is particularly difficult for
      multivitamin use because of the many different formulations available. Therefore,
      many studies simply ask about the frequency of multivitamin use and assign
      default nutrient composition values to obtain nutrient intakes. Multivitamin
      supplements are important contributors to total nutrient intakes, but it is not
      known how default values affect the accuracy of intake estimation. In this study,
      nutrient intakes were calculated from multivitamins consumed by 26,735
      multivitamin users who provided detailed information like product name(s) and
      frequency of use on a mailed questionnaire. We then recalculated the intakes,
      using 2 different assumptions about the composition of the multivitamin
      supplements: 1) a single default composition for all products; and 2) four
      default compositions, 1 for each subtype of multivitamin, i.e., one-a-day with
      minerals, one-a-day without minerals, B-complex or stress multivitamins, and
      antioxidant combinations. A total of 1246 different brands of multivitamins were
      reported and nutrient composition varied widely. Spearman correlation coefficient
      analyses, using the 4 default nutrient profiles compared with actual nutrient
      intakes, were >0.5 (P < 0.001) for 12 of 15 nutrients examined. However,
      correlations using the single default were lower, with only 5 correlations >0.5.
      Our findings suggest that a questionnaire designed to assess the composition
      profiles for 4 types of multivitamin products substantially improves the accuracy
      of nutrient-intake estimates over one that uses a single default nutrient profile
      for all multivitamin products.

PMID- 16614432
TI  - Normalization of energy expenditure data for differences in body mass or
      composition in children and adolescents.
AB  - The most appropriate model for normalization of energy expenditure (EE) data for
      body mass or composition in growing children and adolescents has not been studied
      extensively. In this study, we investigated allometric modeling for the
      normalization of EE data for body mass or composition in a large cohort of
      children (n = 833), ages 5-19 y for a wide range of physical activities.
      Anthropometry was performed by standard techniques, and total body fat-free mass
      (FFM) and fat mass (FM) were determined by dual-energy X-ray absorptiometry
      (DXA). Weight status was defined as nonoverweight or overweight based on the 95th
      percentile for BMI. Total energy expenditure (TEE), basal energy expenditure
      (BEE), sleeping energy expenditure (SEE), and cycling EE were measured during 24
      h room respiration calorimetry. Walking and maximal EE (MaxEE) were measured
      according to a treadmill protocol. Allometric or power function models were used
      to identify appropriate scaling parameters for EE. For BEE and lower levels of
      EE, weight scaled to 0.5. For cycling and treadmill walking/running, the weight
      exponent approached 0.7. Scaling EE for FFM resulted in exponents of 0.6 for
      lower rates of EE and 0.8-1.0 for higher rates of EE. Appropriate scaling of EE
      for body weight and composition of children and adolescents varied primarily as a
      function of the level of EE. In some instances, the exponents for scaling EE by
      body weight or composition were influenced by gender and weight status, but not
      by age.

PMID- 16614431
TI  - The effect of vitamin A supplementation on the intestinal immune response in
      Mexican children is modified by pathogen infections and diarrhea.
AB  - Vitamin A supplementation has consistently reduced infant mortality and the
      severity of pathogen-induced diarrhea. The mechanism by which vitamin A modulates
      the mucosal immune response to produce these effects remains poorly defined. To
      address this issue, stools collected during the summer months from 127 Mexican
      children 5-15 mo old enrolled in a larger, randomized, double-blind, placebo
      controlled, vitamin A supplementation trial were screened for interleukin (IL)-4,
      IL-6, interferon-gamma (IFN-gamma), and gastrointestinal pathogens. Fecal
      cytokine values were categorized into 3 levels (undetectable, <median, > or
      =median). Multinomial regression models were used to determine the probability
      that vitamin A-supplemented children had higher categorical values of a cytokine
      than children in the placebo group. Differences in categorical values were also
      analyzed after stratification by gastrointestinal pathogen infections and
      diarrheal symptoms. Overall, fecal cytokine categorical levels did not differ
      between children randomized to the 2 arms. Vitamin A-supplemented children
      infected with enteropathogenic E. coli (EPEC) had reduced IL-4 and IFN-gamma
      levels [odds ratio (OR) = 0.3, 95% CI 0.13-0.67 and OR = 0.34, 95% CI 0.14-0.83,
      respectively] compared with children in the placebo group. Vitamin A-supplemented
      children had increased IL-4 levels when infected with A. lumbricoides (OR =
      12.06, 95% CI 0.95-153.85). In contrast, IL-4 levels increased (OR = 2.14, 95% CI
      0.94-4.87) and IFN-gamma levels decreased (OR = 0.51, 95% CI 0.26-0.99) among
      vitamin A-supplemented children with diarrhea compared with children in the
      placebo group. These findings suggest that the regulation of the mucosal immune
      response by vitamin A may depend on the type of enteric pathogen infecting the
      child and the presence of clinical symptoms.

PMID- 16614433
TI  - The glycemic load estimated from the glycemic index does not differ greatly from
      that measured using a standard curve in healthy volunteers.
AB  - Glycemic load (GL) is calculated indirectly as glycemic index (GI) times the
      weight of available carbohydrate. Alternatively, GL may be measured directly
      using a standard glucose curve. The purpose of this study was to test the
      agreement between GL values obtained using direct and indirect methods of
      measurement in 20 healthy volunteers. A standard curve in which glucose dose was
      plotted against blood glucose incremental area under the curve (iAUC) was
      generated using beverages containing 0, 12.5, 25, 50, and 75 g glucose. The GI
      and available carbohydrate content of 5 foods were measured. The foods (white
      bread, fruit bread, granola bar, instant potato, and chickpeas) were consumed in
      3 portion sizes, yielding 15 food/portion size combinations. GL was determined
      directly by relating the iAUC of a test food to the glucose standard curve. For
      12 of 15 food/portion size combinations, GL determined using GI x available
      carbohydrate did not differ from GL measured from the standard curve (P > 0.05).
      For 3 of the test products (100 g white bread, and 100- and 150-g granola bars),
      GI x available carbohydrate was higher than the direct measure. Benefits of the
      direct measure are that the method does not require testing for available
      carbohydrate and it allows portion sizes to be tested. For practical purposes, GI
      x available carbohydrate provided a good estimate of GL, at least under
      circumstances in which available carbohydrate was measured, and GI and GL were
      tested in the same group of people.

PMID- 16614434
TI  - Varying levels of food energy self-reporting are associated with between-group,
      but not within-subject, differences in food intake.
AB  - Energy intakes reported in diet diaries are frequently significantly below the
      energy requirements for a weight-stable individual. To investigate the impact of
      low energy reporting on between-group comparisons and within-subject analyses of
      eating behavior, we examined the baseline 7-d food-intake diaries submitted by
      365 male and 564 female free-living normal adult humans. Participants were
      separated into 5 different groups, based upon their levels of energy reporting
      relative to their predicted basal metabolic rate: EI:BMR(est) = 0-0.99, 1.0
      1.199, 1.2-1.399, 1.3-1.599, and > or =1.6. Between-group analysis revealed
      significant inverse relations among reporting level and body weight, BMI,
      cognitive restraint, positive relations with intake, meal size, and meal
      frequency. On the other hand, within-subject analyses suggested that, regardless
      of the level of energy reporting, equivalent relations are found among the
      amounts eaten in meals and the presence of other people, palatability, hunger,
      satiety, dietary energy density, contents of the stomach, time since the last
      meal, and time of day and correlations between daily intake and intake on
      subsequent days. The results suggest that comparing the intakes reported in diet
      diaries by different groups may be confounded by group differences in reporting
      levels. In contrast, the results clearly support the conclusion that diet diary
      data are suitable for assessing the relations between variables assessed within
      subjects irrespective of the level of reporting of energy intake.

PMID- 16614435
TI  - Treatment effects of maternal micronutrient supplementation vary by percentiles
      of the birth weight distribution in rural Nepal.
AB  - Certain antenatal micronutrient supplements increased birth weight by 40-70 g in
      rural Nepal. The effect was estimated by calculating the mean difference in birth
      weight between control and treatment groups, which assumes a constant treatment
      effect across the birth weight distribution. By estimating differences (and CI)
      in birth weight between treatment and control groups as a nonlinear, smooth
      function of the percentiles of the birth weight distribution, we can examine
      whether the shape of the birth weight distribution for a treatment group is
      different from that of the control group. Supplementation groups were folic acid,
      folic acid and iron, folic acid and iron and zinc, and a multiple micronutrient
      supplement all with vitamin A, compared with the control group of vitamin A
      alone. The shape of the birth weight distribution in the multiple micronutrient
      group was the same as that of the control group; however, the location of the
      distribution had shifted. The folic acid and iron group had fewer infants in the
      lower tail of its distribution but a similar proportion in the upper tail
      compared with the control group. The biologic pathways affecting intrauterine
      growth may vary by micronutrients such that some may confer a benefit among the
      most vulnerable infants, whereas others may have a more constant effect across
      the birth weight distribution. Future analytic approaches to estimating benefits
      of maternal supplementation on birth weight should examine whether there is a
      constant or variable treatment effect across the distribution of birth weight.

PMID- 16614436
TI  - Individual weight change is associated with household food security status.
AB  - This study examined the relation between household food security status and
      current measured weight and change in self-reported weight over 12 mo using data
      from the 1999-2000 and 2001-2002 National Health and Nutrition Examination
      Surveys. Current measured BMI categories were as follows: underweight (<18.5
      kg/m(2)), overweight (> or =25 kg/m(2)), and obese (> or =30 kg/m(2)). Change in
      self-reported weight used 2 cut-off points, i.e., a gain/loss of at least 2.27 kg
      (5 lb) and at least 4.54 kg (10 lb). Household food security categories were as
      follows: fully secure, marginally secure, insecure without hunger, and insecure
      with hunger. Multivariate analyses were adjusted for race/ethnicity, household
      income, education level, and current health status. Compared with women in
      households that were fully food secure, women in households that were marginally
      food secure [odds ratio (OR) 1.58] and food insecure without hunger (OR 1.76)
      were significantly more likely to be obese. Compared with women in households
      that were fully food secure, those in households that were marginally food secure
      were significantly more likely to gain at least 4.54 kg (OR 1.68). Compared with
      men in households that were fully food secure, men in households that were
      marginally food secure were more likely to be obese and to gain at least 4.54 kg,
      but these effects were smaller in magnitude than those for women and
      insignificant in some specifications. This study corroborates previous cross
      sectional associations between intermediate levels of food insecurity and obesity
      for women, and it finds an association between intermediate levels of food
      insecurity and 12-mo weight gain for women.

PMID- 16614437
TI  - Measuring household food insecurity: why it's so important and yet so difficult
      to do.
AB  - Food insecurity is a daily reality for hundreds of millions of people around the
      world. Although its most extreme manifestations are often obvious, many other
      households facing constraints in their access to food are less identifiable.
      Operational agencies lack a method for differentiating households at varying
      degrees of food insecurity in order to target and evaluate their interventions.
      This chapter provides an overview of a set of papers associated with a research
      initiative that seeks to identify more precise, yet simple, measures of household
      food insecurity. The overview highlights three main conceptual developments
      associated with practical approaches to measuring constraints in access to food:
      1) a shift from using measures of food availability and utilization to measuring
      "inadequate access"; 2) a shift from a focus on objective to subjective measures;
      and 3) a growing emphasis on fundamental measurement as opposed to reliance on
      distal, proxy measures. Further research is needed regarding 1) how well measures
      of household food insecurity designed for chronically food-insecure contexts
      capture the processes leading to, and experience of, acute food insecurity, 2)
      the impact of short-term shocks, such as major floods or earthquake, on household
      behaviors that determine responses to food security questions, 3) better
      measurement of the interaction between severity and frequency of household food
      insecurity behaviors, and 4) the determination of whether an individual's
      response to survey questions can be representative of the food insecurity
      experiences of all members of the household.

PMID- 16614438
TI  - Development and validation of an experience-based measure of household food
      insecurity within and across seasons in northern Burkina Faso.
AB  - Organizations measure household food insecurity for program design, planning,
      targeting, implementation, monitoring, and evaluation, but existing measures
      often are inadequate. Qualitative and quantitative methods were used to develop
      and validate an experienced-based measure of the access component of food
      insecurity in northern Burkina Faso. In-depth interviews on food insecurity were
      done with 10 household heads and 26 women using interview guides. We identified
      themes, classified households, created a table of food insecurity categories,
      identified items to add to or delete from an initial questionnaire, and developed
      and revised answer choices. A longitudinal study provided quantitative data on
      changes over time in household food insecurity, economic situation, and related
      factors. Data were collected on 126 simple and complex households from 9 villages
      each July and January from 2001 to 2003 (5 waves). These data allowed examination
      of changes in household food insecurity twice annually across the best and worst
      seasons for food, and evaluation of the ability of the experience-based measure
      to differentiate changes in household food insecurity. Validity was assessed by
      examining reliability and by comparing the experienced-based food insecurity
      measure with economic status, dietary, and anthropometric measures and with a
      measure created by an observer who rated the households' food insecurity. The
      results provide strong evidence that the food insecurity score, calculated from
      experience-based questionnaire items, was valid for determining seasonal
      differences in household food insecurity, differences among households in food
      insecurity at a given time, and changes in household food insecurity over time in
      northern rural Burkina Faso.

PMID- 16614439
TI  - Comparison of a qualitative and a quantitative approach to developing a household
      food insecurity scale for Bangladesh.
AB  - This paper compares a qualitative and a quantitative (Rasch) method of item
      assessment for developing the content of a food insecurity scale for Bangladesh.
      Data are derived from the Bangladesh Food Insecurity Measurement and Validation
      Study, in which researchers collected 2 rounds of ethnographic information and 3
      rounds of conventional household survey data between 2001 and 2003. The
      qualitative method of scale development relied on content experts and respondents
      themselves to evaluate household food insecurity items generated through
      ethnographic research. The quantitative method applied the Rasch model to assess
      the fit of the same items using representative survey data. The Rasch model was
      then used to test for differential item functioning (DIF) across diverse
      demographic and geographic subgroups. The qualitative assessment flagged and
      discarded 10 items, leaving 13. The Rasch assessment of infit and outfit flagged
      3 items, and the Rasch DIF test discarded another 10 items, leaving a total of 10
      items in the Rasch-derived scale. The 2 scales contained 8 of the same items. The
      qualitatively and quantitatively derived scales were highly correlated (r = 0.96,
      P < 0.01), and the 2 methods located 90% of households in the same food
      insecurity tercile. This convergence lends added confidence to the use of either
      scale for identifying food-insecure households in different regions of
      Bangladesh. Multiple methods should continue to be applied in a systematic and
      transparent way to lend additional credence to the results when they converge and
      to pinpoint directions for further clarification where they do not.

PMID- 16614440
TI  - Household food insecurity and food expenditure in Bolivia, Burkina Faso, And the
      Philippines.
AB  - This study examined the association between food insecurity, determined by a
      modified version of the U.S. Household Food Security Survey Module (US HFSSM),
      and total daily per capita (DPC) consumption (measured as household expenditures)
      in Bolivia, Burkina Faso, and the Philippines. Household food insecurity was
      determined by an adapted 9-item US HFSSM version. A short version of the World
      Bank's Living Standards Measurement Study (LSMS) consumption module measured
      household expenditures. Focus groups were used to adapt the survey instrument to
      each local context. The sample (n approximately 330 per country) includes
      residents of urban and rural areas. A 12-month food expenditure aggregate was
      generated as part of the total household expenditures calculation. DPC food
      expenditure, which represented over 60% of the total household consumption, as
      well as expenditures on specific food groups correlated with food insecurity both
      as a continuous Food Insecurity Score (FinSS) and a tricategorical food
      insecurity status variable. ANOVA and regression analysis were executed adjusting
      for social and demographic covariates. Food-secure households have significantly
      higher (P < 0.05) total DPC food expenditures as well as expenditures on animal
      source foods, vegetables, and fats and oils than moderately and severely food
      insecure households. The results offer evidence that the US HFSSM is able to
      discriminate between households at different levels of food insecurity status in
      diverse developing world settings.

PMID- 16614441
TI  - Commonalities in the experience of household food insecurity across cultures:
      what are measures missing?
AB  - This paper hypothesizes that there is a common "core" to the household food
      insecurity experience that goes beyond insufficient food quantity and that
      transcends culture. The paper for the first time employs an exploratory approach
      to identify cross-cultural commonalities of the food insecurity experience as
      captured in 22 scales and related ethnographies derived from 15 different
      countries. The constant comparative method was used to code elements of the food
      insecurity experience expressed in the ethnographies and to regroup them into
      domains and subdomains. This typology was then applied to ascertain which
      experiential domains and subdomains were measured (or not) across all 22 studies.
      Survey data from 11 of the studies were then analyzed to assess similarities in
      the relative frequency with which culturally diverse households responded to
      questionnaire items related to these common domains/subdomains. The analysis
      confirmed that insufficient food quantity, inadequate food quality, and
      uncertainty and worry about food were a significant part of the food insecurity
      experience in all sampled cultures; concerns about social unacceptability emerged
      in all ethnographic accounts. Several subdomains were identified, such as concern
      over food safety and meal pattern disruption, with potentially important
      consequences for physical and psychological well-being. The comparative survey
      data showed that the relative frequency at which populations responded to domain
      related questionnaire items was similar across all but a few cultures. Future
      food insecurity assessments should consider these core domains and subdomains as
      the starting point for measures that can generate rich information to inform food
      security policies and programs.

PMID- 16614442
TI  - Development of a universally applicable household food insecurity measurement
      tool: process, current status, and outstanding issues.
AB  - The United States Public Law 480 Title II food aid program is the largest U.S.
      government program directed at reducing hunger, malnutrition, and food insecurity
      in the developing world. USAID and Title II implementing partners face challenges
      in measuring the success of Title II programs in reducing household food
      insecurity because of the technical difficulty and cost of collecting and
      analyzing data on traditional food security indicators, such as per capita income
      and caloric adequacy. The Household Food Insecurity Access Scale (HFIAS) holds
      promise as an easier and more user-friendly approach for measuring the access
      component of household food security. To support the consistent and comparable
      collection of the HFIAS, efforts are under way to develop a guide with a
      standardized questionnaire and data collection and analysis instructions. A set
      of domains have been identified that is deemed to capture the universal
      experience of the access component of household food insecurity across countries
      and cultures. Based on these domains, a set of questions has been developed with
      wording that is deemed to be universally appropriate, with minor adaptation to
      local contexts. These underlying suppositions, based on research in multiple
      countries, are being verified by potential users of the guide. The key remaining
      issue relates to the process for creating a categorical indicator of food
      insecurity status from the HFIAS.

PMID- 16614443
TI  - An antibody-based microarray assay for small RNA detection.
AB  - Detection of RNAs on microarrays is rapidly becoming a standard approach for
      molecular biologists. However, current methods frequently discriminate against
      structured and/or small RNA species. Here we present an approach that bypasses
      these problems. Unmodified RNA is hybridized directly to DNA microarrays and
      detected with the high-affinity, nucleotide sequence-independent, DNA/RNA hybrid
      specific mouse monoclonal antibody S9.6. Subsequent reactions with a
      fluorescently-labeled anti-mouse IgG antibody or biotin-labeled anti-mouse IgG
      together with fluorescently labeled streptavidin produces a signal that can be
      measured in a standard microarray scanner. The antibody-based method was able to
      detect low abundance small RNAs of Escherichia coli much more efficiently than
      the commonly-used cDNA-based method. A specific small RNA was detected in amounts
      of 0.25 fmol (i.e. concentration of 10 pM in a 25 microl reaction). The method is
      an efficient, robust and inexpensive technique that allows quantitative analysis
      of gene expression and does not discriminate against short or structured RNAs.

PMID- 16614444
TI  - Polycistronic RNA polymerase II expression vectors for RNA interference based on
      BIC/miR-155.
AB  - Vector-based RNA interference (RNAi) has emerged as a valuable tool for analysis
      of gene function. We have developed new RNA polymerase II expression vectors for
      RNAi, designated SIBR vectors, based upon the non-coding RNA BIC. BIC contains
      the miR-155 microRNA (miRNA) precursor, and we find that expression of a short
      region of the third exon of mouse BIC is sufficient to produce miR-155 in
      mammalian cells. The SIBR vectors use a modified miR-155 precursor stem-loop and
      flanking BIC sequences to express synthetic miRNAs complementary to target RNAs.
      Like RNA polymerase III driven short hairpin RNA vectors, the SIBR vectors
      efficiently reduce target mRNA and protein expression. The synthetic miRNAs can
      be expressed from an intron, allowing coexpression of a marker or other protein
      with the miRNAs. In addition, intronic expression of a synthetic miRNA from a two
      intron vector enhances RNAi. A SIBR vector can express two different miRNAs from
      a single transcript for effective inhibition of two different target mRNAs.
      Furthermore, at least eight tandem copies of a synthetic miRNA can be expressed
      in a polycistronic transcript to increase the inhibition of a target RNA. The
      SIBR vectors are flexible tools for a variety of RNAi applications.

PMID- 16614445
TI  - Predicting cis-acting elements of Lactobacillus plantarum by comparative genomics
      with different taxonomic subgroups.
AB  - Cis-acting elements in Lactobacillus plantarum were predicted by comparative
      analysis of the upstream regions of conserved genes and predicted transcriptional
      units (TUs) in different bacterial genomes. TUs were predicted for two species
      sets, with different evolutionary distances to L.plantarum. TUs were designated
      'cluster of orthologous transcriptional units' (COT) when >50% of the genes were
      orthologous in different species. Conserved DNA sequences were detected in the
      upstream regions of different COTs. Subsequently, conserved motifs were used to
      scan upstream regions of all TUs. This method revealed 18 regulatory motifs only
      present in lactic acid bacteria (LAB). The 18 LAB-specific candidate regulatory
      motifs included 13 that were not described previously. These LAB-specific
      different motifs were found in front of genes encoding functions varying from
      cold shock proteins to RNA and DNA polymerases, and many unknown functions. The
      best-described LAB-specific motif found was the CopR-binding site, regulating
      expression of copper transport ATPases. Finally, all detected motifs were used to
      predict co-regulated TUs (regulons) for L.plantarum, and transcriptome profiling
      data were analyzed to provide regulon prediction validation. It is demonstrated
      that phylogenetic footprinting using different species sets can identify and
      distinguish between general regulatory motifs and LAB-specific regulatory motifs.

PMID- 16614447
TI  - Aspects of large-scale chromatin structures in mouse liver nuclei can be
      predicted from the DNA sequence.
AB  - The large amount of non-coding DNA present in mammalian genomes suggests that
      some of it may play a structural or functional role. We provide evidence that it
      is possible to predict computationally, from the DNA sequence, loci in mouse
      liver nuclei that possess distinctive nucleosome arrays. We tested the hypothesis
      that a 100 kb region of DNA possessing a strong, in-phase, dinucleosome period
      oscillation in the motif period-10 non-T, A/T, G, should generate a nucleosome
      array with a nucleosome repeat that is one-half of the dinucleosome oscillation
      period value, as computed by Fourier analysis of the sequence. Ten loci with
      short repeats, that would be readily distinguishable from the pervasive bulk
      repeat, were predicted computationally and then tested experimentally. We
      estimated experimentally that less than 20% of the chromatin in mouse liver
      nuclei has a nucleosome repeat length that is 15 bp, or more, shorter than the
      bulk repeat value of 195 +/- bp. All 10 computational predictions were confirmed
      experimentally with high statistical significance. Nucleosome repeats as short as
      172 +/- 5 bp were observed for the first time in mouse liver chromatin. These
      findings may be useful for identifying distinctive chromatin structures
      computationally from the DNA sequence.

PMID- 16614446
TI  - Comparison of characteristics and function of translation termination signals
      between and within prokaryotic and eukaryotic organisms.
AB  - Six diverse prokaryotic and five eukaryotic genomes were compared to deduce
      whether the protein synthesis termination signal has common determinants within
      and across both kingdoms. Four of the six prokaryotic and all of the eukaryotic
      genomes investigated demonstrated a similar pattern of nucleotide bias both 5'
      and 3' of the stop codon. A preferred core signal of 4 nt was evident,
      encompassing the stop codon and the following nucleotide. Codons decoded by hyper
      modified tRNAs were over-represented in the region 5' to the stop codon in genes
      from both kingdoms. The origin of the 3' bias was more variable particularly
      among the prokaryotic organisms. In both kingdoms, genes with the highest
      expression index exhibited a strong bias but genes with the lowest expression
      showed none. Absence of bias in parasitic prokaryotes may reflect an absence of
      pressure to evolve more efficient translation. Experiments were undertaken to
      determine if a correlation existed between bias in signal abundance and
      termination efficiency. In Escherichia coli signal abundance correlated with
      termination efficiency for UAA and UGA stop codons, but not in mammalian cells.
      Termination signals that were highly inefficient could be made more efficient by
      increasing the concentration of the cognate decoding release factor.

PMID- 16614448
TI  - Clerocidin interacts with the cleavage complex of Streptococcus pneumoniae
      topoisomerase IV to induce selective irreversible DNA damage.
AB  - Clerocidin (CL), a diterpenoid natural product, alkylates DNA through its epoxide
      moiety and exhibits both anticancer and antibacterial activities. We have
      examined CL action in the presence of topoisomerase IV from Streptococcus
      pneumoniae. CL promoted irreversible enzyme-mediated DNA cleavage leading to
      single- and double-stranded DNA breaks at specific sites. Reaction required the
      diterpenoid function: no cleavage was seen using a naphthalene-substituted
      analogue. Moreover, drug-induced DNA breakage was not observed using a mutant
      topoisomerase IV (ParC Y118F) unable to form a cleavage complex with DNA.
      Sequence analysis of 102 single-stranded DNA breaks and 79 double-stranded breaks
      revealed an overwhelming preference for G at the -1 position, i.e. immediately 5'
      of the enzyme DNA scission site. This specificity contrasts with that of
      topoisomerase IV cleavage with antibacterial quinolones. Indeed, CL stimulated
      DNA breakage by a quinolone-resistant topoisomerase IV (ParC S79F). Overall, the
      results indicate that topoisomerase IV facilitates selective irreversible CL
      attack at guanine and that its cleavage complex differs markedly from that of
      mammalian topoisomerase II which promotes both irreversible and reversible CL
      attack at guanine and cytosine, respectively. The unique ability to form
      exclusively irreversible DNA breaks suggests topoisomerase IV may be a key
      intracellular target of CL in bacteria.

PMID- 16614449
TI  - Structural model for the multisubunit Type IC restriction-modification DNA
      methyltransferase M.EcoR124I in complex with DNA.
AB  - Recent publication of crystal structures for the putative DNA-binding subunits
      (HsdS) of the functionally uncharacterized Type I restriction-modification (R-M)
      enzymes MjaXIP and MgeORF438 have provided a convenient structural template for
      analysis of the more extensively characterized members of this interesting family
      of multisubunit molecular motors. Here, we present a structural model of the Type
      IC M.EcoR124I DNA methyltransferase (MTase), comprising the HsdS subunit, two
      HsdM subunits, the cofactor AdoMet and the substrate DNA molecule. The structure
      was obtained by docking models of individual subunits generated by fold
      recognition and comparative modelling, followed by optimization of inter-subunit
      contacts by energy minimization. The model of M.EcoR124I has allowed
      identification of a number of functionally important residues that appear to be
      involved in DNA-binding. In addition, we have mapped onto the model the location
      of several new mutations of the hsdS gene of M.EcoR124I that were produced by
      misincorporation mutagenesis within the central conserved region of hsdS, we have
      mapped all previously identified DNA-binding mutants of TRD2 and produced a
      detailed analysis of the location of surface-modifiable lysines. The model
      structure, together with location of the mutant residues, provides a better
      background on which to study protein-protein and protein-DNA interactions in Type
      I R-M systems.

PMID- 16614450
TI  - NMR solution structures of LNA (locked nucleic acid) modified quadruplexes.
AB  - We have determined the NMR solution structures of the quadruplexes formed by
      d(TGLGLT) and d(TL4T), where L denotes LNA (locked nucleic acid) modified G
      residues. Both structures are tetrameric, parallel and right-handed and the
      native global fold of the corresponding DNA quadruplex is retained upon
      introduction of the LNA nucleotides. However, local structural alterations are
      observed owing to the locked LNA sugars. In particular, a distinct change in the
      sugar-phosphate backbone is observed at the G2pL3 and L2pL3 base steps and
      sequence dependent changes in the twist between tetrads are also seen. Both the
      LNA modified quadruplexes have raised thermostability as compared to the DNA
      quadruplex. The quadruplex-forming capability of d(TGLGLT) is of particular
      interest as it expands the design flexibility for stable parallel LNA
      quadruplexes and shows that LNA nucleotides can be mixed with DNA or other
      modified nucleic acids. As such, LNA-based quadruplexes can be decorated by a
      variety of chemical modifications. Such LNA quadruplex scaffolds might find
      applications in the developing field of nanobiotechnology.

PMID- 16614451
TI  - Computer simulation of chaperone effects of Archaeal C/D box sRNA binding on rRNA
      folding.
AB  - Archaeal C/D box small RNAs (sRNAs) are homologues of eukaryotic C/D box small
      nucleolar RNAs (snoRNAs). Their main function is guiding 2'-O-ribose methylation
      of nucleotides in rRNAs. The methylation requires the pairing of an sRNA
      antisense element to an rRNA target site with formation of an RNA-RNA duplex. The
      temporary formation of such a duplex during rRNA maturation is expected to
      influence rRNA folding in a chaperone-like way, in particular in thermophilic
      Archaea, where multiple sRNAs with two binding sites are found. Here we
      investigate possible mechanisms of chaperone function of Archaeoglobus fulgidus
      and Pyrococcus abyssi C/D box sRNAs using computer simulations of rRNA secondary
      structure formation by genetic algorithm. The effects of sRNA binding on rRNA
      structure are introduced as temporary structural constraints during co
      transcriptional folding. Comparisons of the final predictions with simulations
      without sRNA binding and with phylogenetic structures show that sRNAs with two
      antisense elements may significantly facilitate the correct formation of long
      range interactions in rRNAs, in particular at elevated temperatures. The
      simulations suggest that the main mechanism of this effect is a transient
      restriction of folding in rRNA domains where the termini are brought together by
      binding to double-guide sRNAs.

PMID- 16614452
TI  - Proteins surrounding hairpin IIIe of the hepatitis C virus internal ribosome
      entry site on the human 40S ribosomal subunit.
AB  - Binding of the internal ribosome entry site (IRES) of the hepatitis C virus (HCV)
      RNA to the eIF-free 40S ribosomal subunit is the first step of initiation of
      translation of the viral RNA. Hairpins IIId and IIIe comprising 253-302 nt of the
      IRES are known to be essential for binding to the 40S subunit. Here we have
      examined the molecular environment of the HCV IRES in its binary complex with the
      human 40S ribosomal subunit. For this purpose, two RNA derivatives were used that
      bore a photoactivatable perfluorophenyl azide cross-linker. In one derivative the
      cross-linker was at the nucleotide A296 in hairpin IIIe, and in the other at G87
      in domain II. Site-specific introduction of the cross-linker was performed using
      alkylating derivatives of oligodeoxyribonucleotides complementary to the target
      RNA sequences. No cross-links with the rRNA were detected with either RNA
      derivative. The RNA with the photoactivatable group at A296 cross-linked to
      proteins identified as S5 and S16 (major) and p40 and S3a (minor), while no cross
      links with proteins were detected with RNA modified at G87. The results obtained
      indicate that hairpin IIIe is located on the solvent side of the 40S subunit head
      on a site opposite the beak.

PMID- 16614453
TI  - Single question about drunkenness to detect college students at risk for injury.
AB  - OBJECTIVES: To examine the frequency of injuries reported by college students who
      replied affirmatively to the question, "In a typical week, how many days do you
      get drunk?" METHODS: In Fall 2003, a Web-based survey was administered to a
      stratified random sample of 3,909 college students from ten North Carolina (NC)
      universities. Students answered questions regarding alcohol use and its
      consequences. Data were analyzed using multiple logistic regression, controlling
      for within-school clustering of drinking behaviors and adjusting for other
      significant covariates. Adjusted odds ratios (AORs) and 95% confidence intervals
      (CI) were calculated for significant predictors (p < 0.05). RESULTS: Two thousand
      four hundred eighty-eight students reported that they are current drinkers; 1,353
      (54.4%) reported getting drunk at least once in a typical week. Compared with
      students who did not report getting drunk at least once a week, these students
      had higher odds of being hurt or injured at least once as a result of their own
      drinking (AOR = 4.97; 95% CI = 3.47 to 7.09), experiencing a fall from a height
      that required medical treatment (AOR = 2.16; 95% CI = 1.36 to 3.43), and being
      taken advantage of sexually as a result of another's drinking (AOR = 2.59; 95% CI
      = 1.72 to 3.89). Students who reported getting drunk at least one day in a
      typical week also were more likely to cause an injury requiring medical treatment
      to someone else. They had higher odds of causing injury in an automobile crash
      (AOR = 1.84; 95% CI = 1.01 to 3.40), of causing a burn that required medical
      treatment (AOR = 2.85; 95% CI = 1.51 to 5.39), and of causing a fall from a
      height that required medical treatment (AOR = 2.02; 95% CI = 1.01 to 4.04).
      Getting drunk was a better indicator of "self-experienced injury" and of "injury
      caused to someone else" than was binge drinking, for all outcomes (p < 0.05).
      CONCLUSIONS: The single question, "In a typical week, how many days do you get
      drunk?" identifies college students who are at higher than normal risk of injury
      as a result of their own drinking and the drinking of others. Future research
      should assess this question's effectiveness as a screening tool in campus health
      centers and in emergency departments.

PMID- 16614454
TI  - The effects of a physician slowdown on emergency department volume and treatment.
AB  - OBJECTIVES: In February 2003, many physicians in New Jersey participated in a
      work slowdown to publicize large increases in malpractice premiums and generate
      support for legislative reform. It was anticipated that the community physician
      slowdown (hereafter referred to as "slowdown") would increase emergency
      department (ED) visits. The authors' goal was to help others prepare for
      anticipated increases in ED volumes by describing the preparatory staffing
      changes made and quantifying increases in ED volume. METHODS: This was a
      retrospective cohort study performed at a New Jersey suburban teaching hospital
      with 70,000 annual visits. Consecutive patients seen by emergency physicians were
      enrolled. The authors extracted patient visit data from the computerized tracking
      system and analyzed hours worked by personnel, patient volumes, admission rates,
      and patient throughput times. Variables from each day of the slowdown with
      baseline values for the same day of the week for the four weeks before and after
      the slowdown were compared. A Bonferroni correction was used, with p < 0.01
      considered statistically significant. RESULTS: Total patient volume increased 79%
      from baseline (95% confidence interval [CI] = 20% to 137%). Pediatric volume
      increased 223% (95% CI = 171% to 274%). Overall admission rate decreased 29%
      compared with baseline (95% CI = 8% to 51%). Patient throughput times did not
      change significantly. Similar results for these variables were found for the
      second through fourth days of the slowdown. CONCLUSIONS: Emergency department
      visits, especially pediatric visits, increased markedly during the community
      physician slowdown. Anticipatory increases in staffing effectively prevented
      increased throughput times.

PMID- 16614455
TI  - CPR training and CPR performance: do CPR-trained bystanders perform CPR?
AB  - OBJECTIVES: To determine factors associated with cardiopulmonary resuscitation
      (CPR) provision by CPR-trained bystanders and to determine factors associated
      with CPR performance by trained bystanders. METHODS: The authors performed a
      prospective, observational study (January 1997 to May 2003) of individuals who
      called 911 (bystanders) at the time of an out-of-hospital cardiac arrest. A
      structured telephone interview of adult cardiac-arrest bystanders was performed
      beginning two weeks after the incident. Elements gathered during interviews
      included bystander and patient demographics, identifying whether the bystander
      was CPR trained, when and by whom the CPR was performed, and describing the
      circumstances of the event. If CPR was not performed, we asked the bystanders why
      CPR was not performed. Logistic regression was used to calculate odds ratios and
      95% confidence intervals (95% CI) for factors associated with CPR performance.
      RESULTS: Of 868 cardiac arrests, 684 (78.1%) bystander interviews were completed.
      Of all bystanders interviewed, 69.6% were family members of the victims, 36.8% of
      the bystanders had more than a high-school education, and 54.1% had been taught
      CPR at some time. In 21.2% of patients, the bystander immediately started CPR,
      and in 33.6% of cases, someone started CPR before the arrival of emergency
      medical services (EMS). Important overall predictors of CPR performance were the
      following: witnessed arrest (OR = 2.3; 95% CI = 1.4 to 3.8); bystander was CPR
      trained (OR = 6.6; 95% CI = 3.5 to 12.5); bystander had more than a high-school
      education (OR = 2.0; 95% CI = 1.2 to 3.1), or arrest occurred in a public
      location (OR = 3.1; 95% CI = 1.7 to 5.8). These variables were significant
      predictors of CPR performance among CPR-trained bystanders, as was CPR training
      within five years (OR = 4.5; 95% CI = 2.8 to 7.3). Common reasons that the CPR
      trained bystanders cited for not performing CPR were the following: 37.5% stated
      that they panicked, 9.1% perceived that they would not be able to do CPR
      correctly, and 1.1% thought that they would hurt the patient. Surprisingly, only
      1.1% objected to performing mouth-to-mouth resuscitation. CONCLUSIONS: A minority
      of CPR-trained bystanders performed CPR. CPR provision was more common in CPR
      trained bystanders with more than a high-school education and when CPR training
      had been within five years. Previously espoused reasons for not doing CPR (mouth
      to-mouth, infectious-disease risk) were not the reasons that bystanders cited for
      not doing CPR. Further work is needed to maximize CPR provision after CPR
      training.

PMID- 16614456
TI  - Physicians' preparedness for bioterrorism and other public health priorities.
AB  - OBJECTIVES: Potential bioterrorism challenges policy makers to balance competing
      public health priorities. Earlier surveys showed low physician bioterrorism
      preparedness but did not assess physicians' general public health preparedness,
      compare the preparedness of emergency and primary care physicians, or assess
      temporal trends. METHODS: This was a national, cross-sectional, random-sample
      survey conducted in 2003. RESULTS: Overall, 744 of 1,200 eligible physicians
      responded (response rate, 62%). Of these, 58% of emergency physician respondents
      and 48% of primary care physician respondents reported having learned a lot about
      responding to bioterror since September 11, 2001 (p < 0.01). However, only 43% of
      emergency physicians and 21% of primary care physicians agreed they are generally
      "well prepared to play a role in responding to a bioterror attack" (p < 0.001).
      Beliefs about balancing public health priorities were similar among emergency and
      primary care respondents. Seventy-eight percent of respondents believed that
      local health care systems need to be prepared for bioterrorism, and 92% believed
      that local health care systems need to be prepared for natural epidemics. By
      contrast, only 23% and 46% of respondents reported that their local health care
      systems are well prepared for bioterrorism and natural epidemics, respectively.
      Meanwhile, 77% agreed that "influenza is a greater threat to public health than
      bioterrorism," and 21% reported that bioterrorism preparedness efforts are
      diverting resources from more important public health problems. CONCLUSIONS: In
      2003, most emergency and primary care physicians reported that they and their
      local health care systems were not yet well prepared to respond to a bioterror
      attack, and many believed that more resources should go toward preparing for
      natural epidemics. These findings highlight the importance of expanding
      bioterrorism preparedness efforts to improve the public health system more
      broadly.

PMID- 16614457
TI  - Identifying bioethics learning needs: a survey of Canadian emergency medicine
      residents.
AB  - OBJECTIVES: Emergency medicine (EM) postgraduate training programs must prepare
      residents for the ethical challenges of clinical practice. Bioethics curricula
      have been developed for EM residents, but they are based on expert opinion rather
      than resident learning needs. Educational interventions based on identified
      learning needs are more effective at changing practice than interventions that
      are not. The goal of this study was to identify the bioethics learning needs of
      Canadian EM residents. METHODS: A survey-based needs assessment of Canadian EM
      residents was performed between July 2000 and June 2001. Residents were asked to
      identify their learning needs by rating bioethics topics and by relating their
      clinical experiences. Physicians and nurses who work with residents were surveyed
      in a similar manner and also asked to identify the residents' bioethics learning
      needs. RESULTS: A total of 129 EM residents (77% of eligible residents), 94
      physicians, and 87 nurses responded. Residents, physicians, and nurses all
      identified issues in end-of-life care as the greatest bioethics learning needs of
      the residents. Other areas identified as learning needs included negotiating
      consent, capacity assessment, truth telling, and breaking bad news. A learning
      need identified by nurses, but not residents, was the manner in which residents
      interact with patients and colleagues. CONCLUSIONS: This needs assessment
      provides valuable information about the ethical challenges EM residents encounter
      and the ethical issues they believe they have not been prepared to face. This
      information should be used to direct and shape ethics education interventions for
      EM residents.

PMID- 16614458
TI  - Gene expression and specificity in the mature zone of the lobster olfactory
      organ.
AB  - The lobster olfactory organ is an important model for investigating many aspects
      of the olfactory system. To facilitate study of the molecular basis of olfaction
      in lobsters, we made a subtracted cDNA library from the mature zone of the
      olfactory organ of Homarus americanus, the American lobster. Sequencing of the 5'
      end of 5,184 cDNA clones produced 2,389 distinct high-quality sequences
      consisting of 1,944 singlets and 445 contigs. Matches to known sequences
      corresponded with the types of cells present in the olfactory organ, including
      specific markers of olfactory sensory neurons, auxiliary cells, secretory cells
      of the aesthetasc tegumental gland, and epithelial cells. The wealth of neuronal
      mRNAs represented among the sequences reflected the preponderance of neurons in
      the tissue. The sequences identified candidate genes responsible for known
      functions and suggested new functions not previously recognized in the olfactory
      organ. A cDNA microarray was designed and tested by assessing mRNA abundance
      differences between two of the lobster's major chemosensory structures: the
      mature zone of the olfactory organ and the dactyl of the walking legs, a taste
      organ. The 115 differences detected again emphasized the abundance of neurons in
      the olfactory organ, especially a cluster of mRNAs encoding cytoskeletal
      associated proteins and cell adhesion molecules such as 14-3-3zeta, actins,
      tubulins, trophinin, Fax, Yel077cp, suppressor of profilin 2, and gelsolin.

PMID- 16614459
TI  - Hyperphagia, lower body temperature, and reduced running wheel activity precede
      development of morbid obesity in New Zealand obese mice.
AB  - Among polygenic mouse models of obesity, the New Zealand obese (NZO) mouse
      exhibits the most severe phenotype, with fat depots exceeding 40% of total body
      weight at the age of 6 mo. Here we dissected the components of energy balance
      including feeding behavior, locomotor activity, energy expenditure, and
      thermogenesis compared with the related lean New Zealand black (NZB) and obese
      B6.V-Lep(ob)/J (ob/ob) strains (11% and 65% fat at 23 wk, respectively). NZO mice
      exhibited a significant hyperphagia that, when food intake was expressed per
      metabolic body mass, was less pronounced than that of the ob/ob strain. Compared
      with NZB, NZO mice exhibited increased meal frequency, meal duration, and meal
      size. Body temperature as determined by telemetry with implanted sensors was
      reduced in NZO mice, but again to a lesser extent than in the ob/ob strain. In
      striking contrast to ob/ob mice, NZO mice were able to maintain a constant body
      temperature during a 20-h cold exposure, thus exhibiting a functioning cold
      induced thermogenesis. No significant differences in spontaneous home cage
      activity were observed among NZO, NZB, and ob/ob strains. When mice had access to
      voluntary running wheels, however, running activity was significantly lower in
      NZO than NZB mice and even lower in ob/ob mice. These data indicate that obesity
      in NZO mice, just as in humans, is due to a combination of hyperphagia, reduced
      energy expenditure, and insufficient physical activity. Because NZO mice differ
      strikingly from the ob/ob strain in their resistance to cold stress, we suggest
      that the molecular defects causing hyperphagia in NZO mice are located distal
      from leptin and its receptor.

PMID- 16614460
TI  - Strain-dependent pulmonary gene expression profiles of a cystic fibrosis mouse
      model.
AB  - Cystic fibrosis (CF) lung disease severity is influenced by unknown genetic
      factors apart from the disease causative gene, cystic fibrosis transmembrane
      conductance regulator (CFTR). Previous studies have shown the C57BL/6J congenic
      Cftr(-/-) (B6 CF) mouse to develop a fibrotic lung disease compared with both CF
      mice of the BALB/c background and wild-type animals. In this report, gene
      expression profiling with microarrays was used to identify genes differentially
      expressed in the lungs of B6 and BALB CF mice compared with non-CF littermates.
      Seven hundred two genes or expressed sequence tags (ESTs) were identified to be
      differentially expressed between the B6 CF and non-CF control lungs (P < 0.05),
      and, by Gene Ontology classification, the B6 CF response included the cell
      proliferation categories of DNA metabolism and mitosis. In the response of BALB
      mice to nonfunctional Cftr, 943 genes/ESTs were differentially expressed compared
      with controls. The biological processes of apoptosis and T and B cell
      proliferation were prominent in the gene list of the BALB CF strain. In support
      of this strain difference, increased T lymphocyte infiltration was evident in the
      lungs of BALB CF mice, through immunohistochemical staining, compared with the
      lungs from both B6 CF and non-CF control mice. Four hundred forty-four genes/ESTs
      were differentially expressed between B6 CF and BALB CF mice (P < 0.05, fold >
      2), including 56 that map to previously identified linkage intervals. These
      results suggest that the variable severity of CF lung disease in this mouse model
      is controlled by multiple genetic factors, including those of an immune response.

PMID- 16614461
TI  - Early detection of endothelial injury and dysfunction in conjunction with
      correction of hemodynamic maladjustment can effectively restore renal function in
      type 2 diabetic nephropathy.
AB  - This paper was aimed to investigate (1) the early marker of endothelial injury in
      type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the
      therapeutic strategy aiming to restore renal function. Fifty patients (35
      normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was
      collected for determination of circulating vascular endothelial cells (CEC) and
      the serum was prepared for determination of transforming growth factor beta
      (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule.
      Intrarenal hemodynamics and renal function were also assessed. The results showed
      that increased number of circulating EC, elevated TGFbeta and depleted ratio of
      CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a
      hemodynamic maladjustment characterized by preferential constriction of the
      efferent arteriole, intraglomerular hypertension and reduction in peritubular
      capillary flow. It was concluded that early marker of endothelial injury is
      reflected by increasing number of CEC. Such markers correlate with the glomerular
      endothelial dysfunction associated with hemodynamic maladjustment. Early
      detection of endothelial injury and appropriate correction of hemodynamic
      maladjustment by multidrug vasodilators can effectively restore renal function in
      type 2 diabetic nephropathy.

PMID- 16614462
TI  - Rheological properties of erythrocytes in patients suffering from erysipelas.
      Examination with LORCA device.
AB  - The rheological properties of erythrocytes: elongation and the aggregation, as
      well as basic peripheral blood parameters: RBC number, hematocrit, MCV, MCH, MCHC
      reticulocytes, fibrinogen level, ESR, and glucose level were studied in a group
      of erysipelas patients. The concentration of malonyl dialdehyde (MDA) in
      erythrocytes was also measured, as an indicator of oxidative stress exerted. The
      study involved 18 erysipelas patients and 18 healthy subjects. The rheological
      properties and the aggregation of erythrocytes were studied with the use of a
      LORCA instrument (Laser-assisted Optical Rotational Cell Analyser). Differences
      were found in elongation index (EI) between the blood control (C) and patients
      (P), with an increase of this value only at 0.58 Pa shear stress and at 1.13 Pa
      shear stress. Upstroke were used as the indexes of RBC deformability, and the
      following aggregation parameters: intensity of light scattering in the prior
      disaggregation (Isc dis) - C - 43.0 au (arbitrary units), P - 44.8 au, time when
      cells are round and not aggregated (Isc top) - C - 51.6 au, P - 49.3 au, the
      amplitude of aggregation, the difference between Isc max and Isc min (AMP) - C -
      39.9 au, P - 28.7 au, aggregation index (AI) - C - 64.6%, P - 70.0%, time for
      reach one half of the maximum aggregation (t(1/2)) - C - 2.0 s, P - 1.5 s,
      threshold shear stress, the lowest force that breaks the aggregation formed
      (Y(thr)) in P exceed 170% control group were measured. A decrease in the
      elasticity of erythrocytes in erysipelas patients was associated with the
      simultaneous increase of MDA - C - 0.08 nM/mgHb, P - 0.11 nM/mgHb content in the
      membranes of red blood cells. Basic peripheral blood parameters studied in
      patients with erysipelas did not differ significantly from the control group
      except for WBC, fibrinogen (C - 3.8 g/l, P - 7.8 g/l), and ESR (C - 6.1 mm/h, P -
      45.4 mm/h) which were significantly higher.

PMID- 16614463
TI  - Changes in renal hemodynamics in streptozotocin-induced diabetic rats with L
      ascorbic acid supplementation.
AB  - The present study was designed to investigate whether L-ascorbic acid (AA)
      supplementation could prevent changes in renal hemodynamics in diabetic rats or
      not. The experiments were carried out in 48 male Sprague-Dawley rats. Diabetes
      mellitus was induced in rats by intravenous injection with streptozotocin (STZ)
      (55 mg/kg.bw), while the control rats were received citrate buffer alone. The
      renal hemodynamics was examined after the supplementation of AA (1 mg/l) for 8
      and 16 weeks. The results demonstrated that AA could retard the increase (p<0.05)
      in renal vascular resistance (RVR) significantly compared with diabetic rats
      (STZ). Besides, at week 16, the effective renal plasma flow (ERPF) and the
      glomerular filtration rate (GFR) of STZ-AA were significantly higher than those
      of STZ (p<0.05). In conclusion, supplementation of AA was able to ameliorate the
      renal dysfunction in STZ-induced diabetic rats by decrease in RVR concomitant
      with an increase in both ERPF and GFR.

PMID- 16614464
TI  - Relationships between blood rheology and age, body mass index, blood cell count,
      fibrinogen, and lipids in healthy subjects.
AB  - We investigated the relationships between blood rheology assessed by microchannel
      method and the various hemorheologic factors in healthy subjects. One hundred
      seventy-six healthy volunteers (90 men and 86 women, mean age; 32.9+/-11.3 years)
      were participated in this study. Body weight, body mass index, red blood cell
      count, hematocrit, hemoglobin, white blood cell count, and platelet count, plasma
      fibrinogen, and fasting serum lipid and lipoprotein concentrations were measured.
      In order to assess blood rheology, blood passage time was determined by a
      microchannel method (Micro Channel Array Flow Analyzer). Age, body mass index,
      red blood cell count, hematocrit, hemoglobin, white blood cell count, total
      cholesterol, low-density lipoprotein cholesterol, and triglyceride were
      positively correlated with blood passage time in all subjects, respectively
      (p<0.01) and high-density lipoprotein cholesterol was inversely correlated with
      blood passage time (p<0.01). However, platelet count, and fibrinogen were not
      correlated with blood passage time. The present study showed that increased age,
      body mass index, red blood cell count, white blood cell count, total cholesterol,
      low-density lipoprotein cholesterol, and triglyceride and decreased high-density
      lipoprotein cholesterol were associated with impaired blood rheology measured by
      microchannel method in healthy subjects, suggesting that aging, obesity,
      erythrocytosis, leukocytosis, and dyslipidemia may be related to hemorheological
      disorders. This microchannel method may be useful to study blood rheology which
      may be associated with various risk factors of cardiovascular disorders.

PMID- 16614465
TI  - Effect of chronic kidney disease on red blood cell rheology.
AB  - BACKGROUND: Anemia of renal failure is primarily a problem of decreased RBC
      production due to erythropoietin deficiency. RBC survival is also reduced,
      perhaps due to decreased RBC deformability. This study measured blood viscosity
      over a range of shear rates in erythropoietin-treated patients on hemodialysis
      (HD), and compared the findings to matched patients with chronic renal
      insufficiency (CRI) and healthy controls. METHODS: Four groups (control, CRI, non
      diabetic HD, and diabetic HD) of 9 matched subjects were recruited. Blood
      viscosity was measured using a cone-plate viscometer over a variety of shear
      rates (11 to 225 s(-1)). RESULTS: Control subjects had lower viscosity values
      throughout all shear rates when compared to the 3 renal disease groups (P
      value=0.039). A trend was observed to higher levels of renal function being
      associated with decreased blood viscosity in patients with CRI. CONCLUSIONS:
      Patients with kidney disease have increased blood viscosity at all shear rates.
      This may be related to changes in RBC shape and decreased deformability in
      patients with kidney disease, independent of HD- or DM-status. This may have
      implications for strategies to treat anemia in these patients.

PMID- 16614466
TI  - Methylenetetrahydrofolate reductase mutation in subjects with abdominal aortic
      aneurysm subdivided for age.
AB  - The aim of the study was to verify the association between abdominal aortic
      aneurysms (AAA) and methylenetetrahydrofolate reductase (MTHFR) mutation, in
      relation to age. We studied the frequency of the MTHFR 677T allele in two groups
      of AAA patients, over and under 60 years. The first AAA group included 42
      patients (30 men and 12 women) aged between 65 and 75 years; the second AAA group
      included 46 patients (32 men and 14 women) aged between 49 and 59 years; the
      control group included 44 healthy controls (29 men and 15 women) aged between 49
      and 75 years. We examined MTHFR allele frequency and MTHFR genotype using Nuclear
      Laser Medicine. MTHFR allele frequency was significantly increased in AAA
      patients >60 compared to healthy controls and in AAA patients <60 compared to
      those >60. The genotype study showed a difference between controls and AAA
      patients and between AAA patients >60 and those <60. The frequency of MTHFR
      mutation was more elevated in both AAA groups vs controls, but it was more
      elevated in younger patients than in the older ones. This mutation might induce
      an early elastin degradation in the aortic wall.

PMID- 16614467
TI  - Metronidazole improves intestinal microcirculation in septic rats independently
      of bacterial burden.
AB  - To explore the effects of metronidazole (Me) on intestinal microcirculation in
      septic rats, intravital microscopy (IVM) following 16 hours of colon ascendens
      stent peritonitis (CASP model) was used. Four groups of animals were studied:
      control group (sham operation) and CASP group, each with and without Me treatment
      (10 mg/kg i.v.). In order to investigate the substance-specific effects of Me
      independently of the antibacterial effects within a pathologically altered
      microcirculation, a second experimental series with lipopolysaccharide challenge
      (LPS model) was carried out. The LPS model consisted of the four groups (control
      animals and LPS animals (15 mg/kg i.v. LPS from E. coli) with and without Me).
      IVM in the LPS experiments was performed following a two hour observation period.
      Me treated CASP or LPS animals, as compared with untreated, demonstrated
      significant improvement of functional capillary density (FCD) of the intestinal
      wall. The increase in the number of leukocytes firmly adhered to the endothelium
      (leukocyte sticking) in the untreated CASP or LPS animals within the V1 venules
      of the intestinal submucosal layer, was significantly reduced in the Me treated
      animals. In conclusion, Me exerts beneficial anti-bacterial and anti-inflammatory
      effects within the septic microcirculation.

PMID- 16614468
TI  - Gravity sedimentation of leukocytes is partially independent from erythrocyte
      sedimentation.
AB  - Leukocyte function tests are suitable for monitoring the severity of chronic
      inflammatory and acute infectious diseases. The tests usually require time
      consuming leukocyte separation techniques while the original character of
      leukocytes can substantially alter. In contrast, we noted that gravity
      sedimentation properties of leukocytes is simple to measure and it also reflects
      non-specific inflammatory reactions of leukocytes. Our novel test is named
      leukocyte antisedimentation rate (LAR) which is measured by leukocyte counting in
      the upper (U) and lower (L) half of the sedimentation blood column after one-hour
      gravity sedimentation of the whole blood. The formula LAR=100.(U-L)/(U+L) is used
      to calculate the percentage of leukocytes crosses the middle line of
      sedimentation blood column upward during one-hour sedimentation (normal
      range<15%, inter-assay coefficient of variation<5%). In this study we found that
      in vitro pre-treatment of septic patients' blood samples with protamine,
      lidocaine and prednisolone decreased leukocyte antisedimentation rate in a
      concentration dependent manner without effecting erythrocyte sedimentation rate.
      Leukocyte adherence was measured by the retention rate of leukocytes in a nylon
      fibre column. There was a significant positive correlation between leukocyte
      antisedimentation rate and leukocyte adherence (p<0.01), hematocrit (p<0.05),
      erythrocyte sedimentation rate (p<0.05) when blood samples of 35 healthy
      individuals were analysed. We concluded that leukocyte antisedimentation rate in
      septic patients is significantly elevated comparing to healthy controls and as a
      bedside test it can reflect leukocyte involvement in infections. In vitro
      protamine, lidocaine and prednisolone pre-treatment of septic patients' blood
      samples indicates that leukocyte antisedimentation process is partially
      independent from the ongoing erythrocyte sedimentation.

PMID- 16614469
TI  - The relationship between coagulation and the extend of surgery and postoperative
      infection in surgical infants below 6 months of age.
AB  - AIM: First to assess coagulation changes after surgery in children below 6 months
      of age. Second to detect differences attributable to the extent of surgery and
      postoperative infection. MATERIALS AND METHODS: Blood counts, haemoglobin
      concentration (Hb), haematocrit (Ht), prothrombine time (PT), activated partial
      thromboplastine time (aPTT) and thrombelastography (TEG) were studied pre- and
      2+/-1/2 d postoperatively. Patients were divided in 3 groups. I: minor surgery
      without access to the abdomen or thorax (n=51); II: abdominal or thoracic
      interventions (n=24); III: abdominal surgery with postoperative sepsis (n=11).
      RESULTS: Preoperative values of Hb, Ht and INR were related to the age of the
      infant. Postoperatively clot strength and formation rate increased in gr. I
      (p<0.05). In gr. II, clot formation was initiated earlier (p<0.05) even though PT
      decreased (p<0.05). In group III, patients postoperatively developed a tendency
      for hypocoagulability in all TEG-parameters, but not in plasmatic coagulation.
      Postoperative TEG measurements were significantly inferior in gr. III when
      compared to gr. I and II. CONCLUSION: Our findings suggest activation of whole
      blood coagulation in the uncomplicated postoperative period despite of a decrease
      in plasmatic coagulation. In sepsis, only thrombelastography, but not plasmatic
      coagulation was affected.

PMID- 16614471
TI  - Lateral rectus muscle changes after bilateral neonatal labyrinthectomy in the
      ferret.
AB  - The vestibular system is essential to the coordination of eye movements during
      head movements. Exercise, such as the eye movements mediated by the vestibular
      system, is a major factor in the development of muscle fiber types and the
      strength of muscle. In this study, the contents of the inner ear were removed
      (labyrinthectomy) from (LAB) ferrets at postnatal day 10 (P10) and raised with
      control (SHAM) animals. At P30, the lateral rectus muscles (LR) were removed to
      analyze the expression of myosin heavy chain (MHC) isoforms and to measure the
      least diameter of the developmental, slow and fast type muscle fibers. Another
      set of animals were sacrificed at P120 to analyze MHC isoform expression and
      muscle fiber diameters, as well as the contractile characteristics of the LR were
      measured prior to sacrifice. The average LAB LR was significantly stronger than
      the SHAM LR and the muscle fibers of the LAB animals were larger in diameter. The
      LAB animals expressed more type IIx and less slow type MHC. These results support
      the hypothesis that input from the inner ear influence the development of
      strength and muscle diameter in the ferret extraocular muscles.

PMID- 16614473
TI  - Effect of fluid forcing on vestibular hair bundles.
AB  - A dynamic 3-D hair bundle model including inertia and viscous fluid drag effects
      based on the finite element method is presented. Six structural components are
      used to construct the hair bundle--kinocilium, stereocilia, upper lateral links,
      shaft links, tip links, and kinocilial links. Fluid drag is distributed on the
      surface of cilia columns. Bundle mechanics are analyzed under two distinct
      loading conditions: (1) drag caused by the shear flow of the surrounding
      endolymph fluid (fluid-forced), (2) a single force applied to the tip of the
      kinocilium (point-forced). A striolar and a medial extrastriolar vestibular hair
      cell from the utricle of a turtle are simulated. The striolar cell bundle shows a
      clear difference in tip link tension profile between fluid-forced and point
      forced cases. When the striolar cell is fluid forced, it shows more evenly
      distributed tip link tensions and is far more sensitive, responding like an
      on/off switch. The extrastriolar cell does not show noticeable differences
      between the forcing types. For both forcing conditions, the extrastriolar cell
      responds serially--the nearest tip links to the kinocilium get tensed first, then
      the tension propagates to the farther tip links.

PMID- 16614472
TI  - Neonatal bilabyrinthectomy leads to changes in skeletal muscle fiber form and
      function.
AB  - Children with hypoactive semicircular canals commonly have delayed motor
      development. We studied ferrets whose vestibular labyrinths were removed at
      postnatal day 10 (P10) to evaluate 1) development of motor behavior, 2) soleus
      contractile characteristics, 3) muscle fiber diameter, and 4) the expression of
      myosin heavy chain (MHC) isoforms. At P30 labyrinthectomized (LAB) ferrets
      exhibited a significant delay in motor development. At P120, the LAB ferrets
      continued to have significantly more difficulty with dynamic balance than the
      SHAM ferrets. At P30, the muscle fibers were about the same diameter as those in
      the sham operated ferrets (SHAM) at the same age but significantly more
      developmental MHC isoforms were expressed in the LAB soleus muscle. At P120, both
      the LAB soleus and medial gastrocnemius expressed significantly more type IIX
      MHC. The P120 LAB soleus muscle was significantly weaker and the muscle fibers
      were significantly smaller. These results support the hypothesis that vestibular
      receptors are important to the development of upright posture and balance
      activities, and influence muscle fiber development and MHC expression in postural
      muscles.

PMID- 16614470
TI  - Development and evolution of the vestibular sensory apparatus of the mammalian
      ear.
AB  - Herein, we will review molecular aspects of vestibular ear development and
      present them in the context of evolutionary changes and hair cell regeneration.
      Several genes guide the development of anterior and posterior canals. Although
      some of these genes are also important for horizontal canal development, this
      canal strongly depends on a single gene, Otx1. Otx1 also governs the segregation
      of saccule and utricle. Several genes are essential for otoconia and cupula
      formation, but protein interactions necessary to form and maintain otoconia or a
      cupula are not yet understood. Nerve fiber guidance to specific vestibular end
      organs is predominantly mediated by diffusible neurotrophic factors that work
      even in the absence of differentiated hair cells. Neurotrophins, in particular
      Bdnf, are the most crucial attractive factor released by hair cells. If Bdnf is
      misexpressed, fibers can be redirected away from hair cells. Hair cell
      differentiation is mediated by Atoh1. However, Atoh1 may not initiate hair cell
      precursor formation. Resolving the role of Atoh1 in postmitotic hair cell
      precursors is crucial for future attempts in hair cell regeneration. Additional
      analyses are needed before gene therapy can help regenerate hair cells, restore
      otoconia, and reconnect sensory epithelia to the brain.

PMID- 16614474
TI  - Full-body gaze control mechanisms elicited during locomotion: effects of VOR
      adaptation.
AB  - We have previously shown that multiple, interdependent, full- body sensorimotor
      subsystems aid gaze stabilization during locomotion. In the present study we
      investigated how the full-body gaze control system responds following exposure to
      visual-vestibular conflict known to adaptively modify vestibulo-ocular reflex
      (VOR) function. Subjects (n = 14) walked (6.4 km/h) on a motorized treadmill
      before and after they were exposed to 0.5X minifying lenses worn for 30 minutes
      during self-generated sinusoidal vertical head rotations performed while seated.
      Results indicate that, following the exposure the major changes that subjects
      showed were to: 1) decrease the amplitude of head pitch and vertical translation
      of the torso movement with respect to space; 2) increase the amount of knee and
      ankle flexion during the initial stance phase of the gait cycle. A correlation
      analysis showed that: 1) changes in the head pitch significantly co-varied with
      that of the vertical torso translation 2) changes in the knee flexion
      significantly co-varied with that of the ankle flexion during the initial stance
      phase of the gait cycle 3) changes in the vertical torso translation
      significantly co-varied with that of the ankle flexion during the initial stance
      phase of the gait cycle. Thus we infer that the changes in the magnitude after
      VOR adaptation in comparison to their pre adaptation responses serve to aid gaze
      stabilization during locomotion. The significant covariation of the changes
      between subsystems provides further evidence that the full body contributes to
      gaze stabilization during locomotion, and its different functional elements are
      subject to adaptive reorganization following exposure to visual-vestibular
      conflict.

PMID- 16614475
TI  - Pulse-step-sine rotation test for the identification of abnormal vestibular
      function.
AB  - This study illustrates the use of a novel "pulse-step-sine" (PSS) rotational
      stimulus to identify abnormal function of the horizontal semicircular canals in
      human subjects with unilateral and bilateral vestibular deficits. The cyclic PSS
      stimulus includes a "bias component" and a "probe component". The bias component,
      consisting of a short duration pulse of acceleration followed by an acceleration
      step, is designed to produce a large change in canal afferent discharge rates
      that silences the neural activity in one canal during the step portion of the PSS
      stimulus. The pulse and step components are then repeated with opposite sign to
      silence afferent activity in the opposite canal. The probe component, consisting
      of a approximately 1 Hz sine wave superimposed on the step portions of the
      stimulus, is designed to test the ability of canal afferents in the excited canal
      to encode the probe stimulus. Various response measures are developed that
      characterize the horizontal slow phase eye movements evoked by the PSS stimulus.
      Results show that these measures can distinguish subjects with normal vestibular
      function from those with unilateral and bilateral vestibular loss, can identify
      the side-of-lesion in subjects with well compensated unilateral vestibular loss,
      and can possibly identify the side-of-greater-loss in subjects with asymmetric
      bilateral loss.

PMID- 16614476
TI  - Control of sway using vibrotactile feedback of body tilt in patients with
      moderate and severe postural control deficits.
AB  - We evaluated the effect of the vibrotactile display of body tilt upon the
      postural stability of vestibulopathic subjects during standing. Two groups were
      studied: those with moderate and with severe deficits as defined by postural
      stability test scores. They were studied under conditions of distorted sensory
      input, and during anterior-posterior perturbations. Seventeen subjects, with uni-
      or bilateral vestibular deficits, as determined by electronystagmography and
      vertical axis rotation, were tested using Equitest computerized dynamic
      posturography (CDP). Based on their performance on the CDP they were divided into
      two groups having either moderate (nine subjects) or severe (eight subjects)
      postural control deficits. Their anterior-posterior (A/P) body motion at the
      waist was measured with a micromechanical rate gyroscope and a linear
      accelerometer. The resulting tilt estimate was displayed by a vibrotactile array
      attached to the torso. The vibration served as a tilt feedback to the subject.
      The subject's performance was evaluated using the root-mean-square (RMS) of both
      the A/P body motion and center-of-pressure (CoP) estimates. Sensory distortions
      were introduced using the Equitest Sensory Organization Tests (SOT). These tests
      are designed to distort A/P sensory inputs while standing. The SOT 5 distorts
      proprioceptive information about ankle joint movement, while the subject stands
      eyes-closed on a moving support platform that measures foot pressure. The SOT 6
      adds distorted visual information about body movement instead of testing with
      eyes closed. Perturbations were introduced using the Equitest Motor Control Tests
      (MCT). These move the support platform forward or backward with small, medium and
      large displacements in the horizontal plane while measuring subjects' foot
      pressure responses. We used the medium and large backward tests. Vibrotactile
      display of body tilt reduced the subjects' A/P sway and improved their balance.
      The finding was more evident for those subjects with severe deficits than those
      moderate ones. This trend was found for both SOT 5 and 6, as well as the medium
      and large MCT. Additionally, during the MCT, the peak deflection and mean
      recovery time also decreased significantly.

PMID- 16614477
TI  - Vestibular function in migraine-related dizziness: a pilot study.
AB  - Migraine-related dizziness (MRD) refers to a disorder in which vestibular
      symptoms are an integral part of migraine symptomatology. The purpose of this
      study was to better define the pathophysiology of MRD, which is incompletely
      understood and to generate hypotheses regarding MRD by assessing the semicircular
      canal-ocular reflex, the otolith-ocular reflex, visual-vestibular interaction,
      vestibulo-spinal function, and visually induced postural sway. Subjects included
      five subjects with MRD, five subjects with migraine without dizziness, and five
      headache-free controls. Subjects with migraine were tested interictally. Results
      indicated that the mean gain of the semicircular canal-ocular reflex during both
      sinusoidal and constant velocity rotation was reduced in subjects with MRD. No
      changes were noted in the dynamics of the semicircular canal-ocular reflex. The
      otolith-ocular reflex, assessed with constant velocity OVAR, indicated that
      subjects with MRD showed a larger modulation component. No group differences were
      found in the bias component during constant velocity OVAR, nor in semicircular
      canal-otolith interaction or visual-vestibular interaction. Computerized dynamic
      posturography indicated that subjects with MRD demonstrated a surface-dependent
      pattern. Postural sway during optic flow indicated that subjects with MRD swayed
      more than the other subjects. We hypothesize that competing processes of
      serotonergic excitation and inhibition alter central vestibular pathways
      differently for semicircular canal vs. otolithic responses and for vestibulo
      ocular vs. vestibulo-spinal pathways.

PMID- 16614478
TI  - Effect of partially hydrolyzed soluble glucan produced by glucosyltrasferases of
      Streptococcus mutans on stimulating human T cell.
AB  - Soluble glucan, which was obtained from action of glucosyltransferases (GTFs) of
      Streptococcus mutans on sucrose, was partially hydrolyzed by acetic acid and
      examined for human T lymphoblast (MOLT-4) stimulating activity. Addition of the
      partially hydrolyzed glucan (15-60 microg/ml) stimulated human T cell (39-65%) in
      a dose dependant manner according to MTT assay. Production of interleukine-2 (IL
      2) and interleukine-2 receptor (IL-2R) from T cell was increased by 44.5 and 25%,
      respectively, by addition of partially hydrolyzed glucan (15 microg/ml). These
      results indicate that stimulation of human T cells by hydrolyzed glucan is
      probably caused by its effects on stimulating gene expression of IL-2 and IL-2R
      of human T cell.

PMID- 16614479
TI  - Induction of quinone reductase by allylisothiocyanate (AITC) and the N
      acetylcysteine conjugate of AITC in Hepa1c1c7 mouse hepatoma cells.
AB  - Cruciferous vegetables contain a series of relatively unique secondary
      metabolites of amino acids, called glucosinolates, from which isothiocyanates
      (ITC) can be generated. While glucosinolates are not thought to be bioactive
      directly, ITC appear to have anticarcinogenic activity. Sinigrin, the predominant
      aliphatic glucosinolate in cruciferous vegetables, is hydrolyzed to yield
      allylisothiocyanate (AITC), which, following absorption and metabolism in humans,
      is excreted in the urine as an N-acetyl-cysteine (NAC) conjugate. AITC possesses
      numerous biochemical and physiological activities. This study examined the
      induction of quinine reductase (QR) by AITC and synthetic AITC-NAC in Hepa1c1c7
      murine hepatoma cells. AITC and AITC-NAC inhibited cell growth in a dose
      dependent manner. The induction of QR activity and QR mRNA expression was dose
      responsive over a range of 0.1-2.5 microM. AITC caused 2.0- and 3.1-fold
      inductions of QR with 1- and 2-microM treatments, respectively. By comparison, 1
      and 2 microM AITC-NAC caused 2.9- and 3.7-fold inductions of QR, respectively.
      Considering the potential of ITC to prevent cancer, these results provide a basis
      for the use of NAC-ITC conjugates as chemopreventive agents.

PMID- 16614480
TI  - Inhibitory effect of the coffee diterpene kahweol on carrageenan-induced
      inflammation in rats.
AB  - Previous studies reported that kahweol, a coffee-specific diterpene, inhibits
      cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression in
      cultured lipopolysaccharide-activated macrophages. The aim of this study was to
      confirm the anti-inflammatory effects of kahweol by examining its effect on the
      inflammatory response induced by carrageenan in a rat using an acute air pouch
      inflammation model. Kahweol significantly reduced the levels of the inflammatory
      process markers in the air pouch, such as the volume of exudates, the amount of
      protein and the number of leukocytes and neutrophils. The levels of nitrite, TNF
      alpha and prostaglandin E2 (PGE2) were also markedly lower in the air pouch of
      the kahweol-treated animals than in the controls. Immunoblot analysis showed that
      kahweol reduced the COX-2 and iNOS expression level in the exudate cells. The
      histological examination showed that there was a lower inflammatory response in
      the pouch tissues from the kahweol-treated animals. In addition, kahweol
      significantly reduced the paw edema induced by carrageenan and also markedly
      reduced the level of PGE2 production in the inflamed paw. These results suggest
      that kahweol has significant anti-inflammatory effects in vivo, which might be
      due to the inhibition of iNOS and COX-2 expression in the inflammatory sites.

PMID- 16614481
TI  - Evaluation of chemopreventive action of Ginsenoside Rp1.
AB  - We evaluated the chemopreventive properties of Ginsenoside Rp1 on 7,12-Dimethyl
      benz (a) anthracene (DMBA) skin papillomagenesis in Swiss albino mice. A
      significant reduction in values of tumor incidence, tumor burden, and cumulative
      number of papilloma was observed in mice treated orally with Ginsenoside Rp1
      continuously at pre-, peri- and post-initiational stages of papillomagenesis as
      compared to the control group. Chemopreventive potential of Ginsenoside Rp1 was
      also observed on the skin metabolizing enzymes in Swiss albino mice. Ginsenoside
      Rp1 produced a significant elevation in the skin microsomal cytochrome p-450 and
      cytochrome b5, glutathione S-transferase (GST), reduced glutathione (GSH),
      glutathione peroxidase (GPX), glutathione reductase (GR), DT-diaphorase,
      superoxide dismutase (SOD) and catalase levels in the group of mice treated with
      Ginsenoside Rp1 for seven consecutive days. However, there was significant
      decrease in lipid peroxidation (LPO) level in Ginsenoside Rp1 treated group.

PMID- 16614482
TI  - Vitamin B12 and methionine synthesis: a critical review. Is nature's most
      beautiful cofactor misunderstood?
AB  - The mechanism by which Vitamin B12 prevents demyelination of nerve tissue is
      still not known. The evidence indicates that the critical site of B12 function in
      nerve tissue is in the enzyme, methionine synthase, in a system which requires S
      adenosylmethionine. In recent years it has been recognized that S
      adenosylmethionine gives rise to the deoxyadenosyl radical which catalyzes many
      reactions including the rearrangement of lysine to beta-lysine. Evidence is
      reviewed which suggests that there is an analogy between the two systems and that
      S-adenosyl methionine may catalyze a rearrangement of homocysteine on methionine
      synthase giving rise to iso- or beta-methionine. The rearranged product is
      readily degraded to CH3-SH, providing a mechanism for removing toxic
      homocysteine.

PMID- 16614483
TI  - Aqueous extract of Ilex paraguariensis attenuates the progression of
      atherosclerosis in cholesterol-fed rabbits.
AB  - Ilex paraguariensis aqueous extract (mate) is an antioxidant-rich beverage widely
      consumed in South American countries. Here we questioned whether mate could
      reduce the progression of atherosclerosis in 1% cholesterol-fed rabbits. New
      Zealand White male rabbits (n = 32) were divided into four groups: control (C, n
      = 5), control-mate (CM, n = 5), hypercholesterolemic (HC, n = 11) and
      hypercholesterolemic-mate (HCM, n = 11). The daily water and mate extract
      consumption was approximately 400 ml. After 2 months of treatment, mate intake
      did not change the lipid profile or hepatic cholesterol content of control or
      hypercholesterolemic rabbits (p < 0.05). However, the atherosclerotic lesion area
      was considerably smaller in the hypercholesterolemic-mate group (HCM, 35.4% vs.
      HC, 60.1%; p < 0.05). In addition, the aortic cholesterol content was around half
      that of the HC group (HCM, 36.8 vs. HC, 73.9 microg/mg of protein, p < 0.05). In
      spite of this, the thiobarbituric acid-reactive substances (TBARS) in the
      atherosclerotic aorta, liver and serum, and the activity of the antioxidant
      enzymes in liver and aorta did not differ among groups (p > 0.05). The results
      showed that Ilex paraguariensis extract can inhibit the progression of
      atherosclerosis in cholesterol-fed rabbits, although it did not decrease the
      serum cholesterol or aortic TBARS and antioxidant enzymes.

PMID- 16614484
TI  - Available lysine content in human milk: stability during manipulation prior to
      ingestion.
AB  - Available lysine content is an indicator of protein quality and nutritional value
      of milk. Many studies have examined the effects of extraction, treatment and
      storage of human milk upon its components, though no references are found
      regarding the possible changes in milk quality as defined by its content in
      essential amino acids such as lysine. The present study investigates the
      available lysine content in human milk and the variations in lysine resulting
      from milk manipulation as follows: (a) Cold storage (refrigeration at 4 degrees C
      for 48 hours, and frozen for 15 days at -20 degrees C); (b) Thermal treatment
      under conditions of low (Holder)(63 degrees C/30 minutes) and high pasteurization
      (75 degrees C/15 seconds). The results obtained show a decrease in milk lysine
      concentration after storage in both refrigerated and frozen samples.
      Pasteurization causes a highly significant loss of available lysine. The lysine
      losses were greater on applying low pasteurization versus the more gentle
      conditions of high pasteurization. CONCLUSIONS: While manipulation through cold
      storage or thermal treatment does not affect the protein content of human milk,
      its protein quality is modified. When human milk must be subjected to
      hygienization, it is preferable to apply high temperature treatment (75 degrees
      C, 15 seconds) than habitual pasteurization (63 degrees C, 30 minutes).

PMID- 16614485
TI  - S-allyl cysteine attenuated CCl4-induced oxidative stress and pulmonary fibrosis
      in rats.
AB  - This study examined effects of S-allyl cysteine (SAC) on carbon tetrachloride
      (CCl4)-induced interstitial pulmonary fibrosis in Wistar rats. CCl4 (0.5 ml/kg)
      was intraperitoneally injected into rats twice a week for 8 weeks, and SAC (50,
      100, or 200 mg/kg), N-acetyl cysteine (NAC, 200 or 600 mg/kg), or L-cysteine
      (CYS, 600 mg/kg) were orally administrated to rats everyday for 8 weeks. SAC
      significantly reduced the increases of transforming growth factor beta, lipid
      peroxides, AST, and ALT in plasma, induced by CCl4. Although CCl4 is mainly
      metabolized by hepatic cytochrome P450, CCl4 induced systemic inflammation and
      some organ fibrosis. SAC dose-dependently and significantly attenuated CCl4
      induced systemic inflammation and fibrosis of lung. SAC also inhibited the
      decrease of thiol levels, the increase of inducible nitric oxide synthase
      expression, the infiltration of leukocytes, and the generation of reactive oxygen
      species in lungs. Although NAC and CYS attenuated CCl4-induced pulmonary
      inflammation and fibrosis, the order of preventive potency was SAC > NAC > CYS
      according to their applied doses. These results indicate that SAC is more
      effective than other cysteine compounds in reducing CCl4-induced lung injury, and
      might be useful in prevention of interstitial pulmonary fibrosis.

PMID- 16614486
TI  - Robert Crispin Evans (1909-2005).

PMID- 16614487
TI  - Interpenetration of homogeneous sphere packings and of two-periodic layers of
      spheres.
AB  - All systems of interpenetrating sphere packings that occur with highest symmetry
      in the cubic, hexagonal or tetragonal crystal family are tabulated. Homogeneous
      sphere packings belonging to 49 different types may be intertwined to systems of
      interpenetrating sphere packings belonging to 74 types. For all compatible
      lattice complexes, the coordinate and lattice parameters are given. The
      corresponding patterns of interpenetration are analysed. For the interpenetration
      of two, three, four, five and eight sphere packings, eleven, three, five, one and
      two different patterns, respectively, are distinguished. In addition, four types
      of interpenetrating layers of spheres were found. Each such sphere configuration
      splits into two or three subsets of parallel sphere layers with an angle of 90
      degrees or of 120 degrees , respectively, between the directions of the normals
      of the layers. A single sphere layer corresponds either to a honeycomb net or to
      a net built up from quadrangles and octagons.

PMID- 16614488
TI  - Spectral decomposition of the linear elastic tensor for trigonal symmetry;
      classification of symmetry restrictions for arbitrary point groups.
AB  - The linear compliance tensor for trigonal symmetry has four different
      eigenvalues, two of which have multiplicity 1, the others multiplicity 2. They
      and the corresponding eigenvectors have been calculated in terms of the seven
      parameters of the corresponding Voigt matrix. Necessary and sufficient conditions
      have been derived for these components to guarantee positive eigenvalues and thus
      a positive strain energy. The hierarchy of restrictions on the linear elastic
      tensors that follow from Neumann's principle for arbitrary point groups in three
      dimensions has been established for the standard choice of the Cartesian
      coordinate system, as well as in coordinate-independent form.

PMID- 16614489
TI  - Multiple diffraction in the kinematical approach.
AB  - The expressions derived for the calculation of multiple diffraction patterns for
      a perfect crystal in the framework of the kinematical theory are compared with
      the relevant result of the kinematical power-transfer equation deduced for a
      mosaic crystal. It is shown that the results of the two concepts differ
      appreciably.

PMID- 16614490
TI  - Enumeration of polytypes MX and MX2 through the use of the symmetry of the
      Zhdanov symbol.
AB  - The different close-packed polytypes MX and MX2 have been enumerated for each of
      the possible space groups by counting the corresponding Zhdanov symbols for each
      space group and period of stacking, P, by the use of elementary combinatorial
      techniques. In special cases, simple closed formulae are obtained for these
      numbers as functions of P. The symmetry properties of the Zhdanov symbol have
      been investigated with the help of its cyclotomic representation and the two
      color symmetry point group thereof. Zhdanov-like rules have been developed for
      MX2 polytypes. The SiC cases have been generated to P = 18 under the ;1
      exclusion' rule and the possible diamond polytypes have been examined.

PMID- 16614491
TI  - Zhdanov's rules work both ways.
AB  - The relationship between the space-group symmetry of a close packing of equal
      balls of repeat period P and the symmetry properties of its representing Zhdanov
      symbol is analyzed. Proofs are straightforward when some symmetry is assumed for
      the stacking, and it is investigated how this symmetry is reflected in the
      structure of the Zhdanov symbol. Most of these proofs are documented in the
      literature, with variable degrees of rigor. However, the proof is somewhat more
      involved when working backwards, i.e. when some symmetry properties for the
      Zhdanov symbol are assumed and the corresponding effect on the symmetry of the
      polytype structure it represents is investigated, which may explain why these
      proofs are avoided or shrugged off as ;easily seen', 'obvious' and the like.

PMID- 16614492
TI  - Precise measurement of local strain fields with energy-unfiltered convergent-beam
      electron diffraction.
AB  - A simple and robust method to precisely determine local strain fields using
      energy-unfiltered convergent-beam electron diffraction is presented. This method
      involves the subtraction of background intensity, the extraction of higher-order
      Laue-zone lines by tracing using a Radon transformation and a system of
      analytical strain determination without the need for an optimization routine such
      as chi2-based minimization. As an example, the measurement of residual strain in
      a silicon-on-insulator wafer is demonstrated. It is found from micro-Raman
      spectroscopy analysis that, at the nanometre scale, this measurement succeeds
      with an accuracy of 0.06%.

PMID- 16614493
TI  - Theoretical structure factors for selected oxides and their effects in high
      resolution electron-microscope (HREM) images.
AB  - A reasonably detailed analysis of the effects of charge redistribution on both X
      ray and electron structure factors as well as for high-resolution electron
      microscope images are presented for a series of light-element oxides. The charge
      redistribution leads to differences of 2-3% for the X-ray structure factors and 5
      7% for electron structure factors in the 0-0.5 A(-1) region. There are detectable
      changes in images of about 10% of the contrast, somewhat dependent upon the
      alignment of atom columns, specimen thickness and defocus. These studies suggest
      that charge redistribution may be detectable using a Cc-limited aberration
      corrected microscope with a specimen thickness of about 50 A.

PMID- 16614494
TI  - Invarioms for improved absolute structure determination of light-atom crystal
      structures.
AB  - The determination of molecular absolute configuration from an X-ray analysis for
      structures that contain only light elements is challenging owing to the weak
      anomalous dispersion signal. The achievable precision of the Flack x parameter
      for such structures is therefore limited, especially when the independent-atom
      model is employed. Invariom modelling can improve this situation. Invarioms are
      theoretically predicted pseudoatoms within the Hansen & Coppens multipole
      formalism. They are transferable from one molecule to another and provide
      generalized aspherical atomic form factors. It is shown that, by application of
      the invariom approach, the precision and standard uncertainty of the Flack x
      parameter and therefore the reliability of deducing molecular chirality in an
      absolute structure determination can be improved.

PMID- 16614495
TI  - Finding optimal radial-function parameters for S atoms in the Hansen-Coppens
      multipole model through refinement of theoretical densities.
AB  - The multipolar model of the valence-electron-density distribution for S atoms has
      been optimized based on theoretical structure factors for six organic molecules.
      The evaluation of different sets of radial function parameters shows that: (a)
      the ratio of the n(l) values for different l is more important than their
      absolute values, as parallel changes in all n(l) for a given atom are compensated
      for by a change in the refined value of the kappa' parameter, and (b) the
      (2,4,6,8) set of n(l) with kappa' refined as a single value is an optimal choice
      of radial function parameters for S atoms.

PMID- 16614496
TI  - On a simple tiling of Deza and Shtogrin.
AB  - Some properties of an exceptional simple tiling by fullerenes, first described by
      Deza & Shtogrin [Southeast Asian Math. Soc. Bull. (1999), 23, 1-11], are
      presented.

PMID- 16614497
TI  - On the symmetry of simple 16-hedra.
AB  - The symmetry point group statistics for all combinatorially non-isomorphic convex
      simple 16-hedra (17490241 in total) are contributed in the paper for the first
      time. The most symmetrical polyhedra with 6 to 56 automorphism group orders (165
      in total) are drawn in Schlegel diagrams and characterized by facet symbols and
      symmetry point groups.

PMID- 16614498
TI  - The current status of asthma in Korea.
AB  - A systematic review of English and Korean articles published between 1990 and
      2004 and a search of database and various online resources was conducted to
      determine the prevalences, mortality rates, socioeconomic burden, quality of
      life, and treatment pattern of asthma in Korean adults and children. Asthma
      morbidity and mortality in Korea are steadily increasing. The prevalence of
      asthma in Korea is estimated to be 3.9% and its severity is often underestimated
      by both physicians and patients. Mortality resulting from chronic lower
      respiratory diseases including asthma increased from 12.9 to 22.6 deaths per
      100,000 of the population between 1992 and 2002. Disease severity, level of
      control, and symptom state were all found to negatively impact the quality of
      life of asthmatics. Although international and Korean asthma management
      guidelines are available, familiarity with and implementation of these guidelines
      by primary care physicians remain poor.

PMID- 16614499
TI  - Synergy of arbekacin-based combinations against vancomycin hetero-intermediate
      Staphylococcus aureus.
AB  - This study was undertaken to evaluate the in vitro activities of arbekacin-based
      combination regimens against vancomycin hetero-intermediate Staphylococcus aureus
      (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin
      sulbactam, teicoplanin, or quinupristin-dalfopristin against seven hetero-VISA
      strains and two methicillin-resistant S. aureus strains were evaluated by the
      time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or
      ampicillin-sulbactam showed the synergistic interaction against hetero-VISA
      strains. Data suggest that these arbekacin-based combination regimens may be
      useful candidates for treatment options of hetero-VISA infections.

PMID- 16614500
TI  - Genetic diversity and exotoxin A production of group A streptococci causing
      sepsis.
AB  - The M protein and streptococcus pyrogenic exotoxin (SPE A) are important
      virulence factors in group A streptococci (GAS) infections. The emm types of GAS
      strains isolated from patients with sepsis were determined by sequencing the 5' N
      terminus of the emm gene, encoding the M protein, and clonality analysis using
      pulsed-field gel electrophoresis. The presence of speA and production of SPE A
      were also examined. There were no predominant GAS clones. The emm genotypes were
      variable, and the most common genotype was emm13 (17.9%). The production
      prevalence of SPE A was 21.4%. The low mortality rate (7.1%) of GAS sepsis might
      be attributable to the low incidence of virulent strains such as emm1 (10.7%) and
      emm3 (7.1%), as well as to low production rate of SPE A.

PMID- 16614501
TI  - Current trends of infectious complications following hematopoietic stem cell
      transplantation in a single center.
AB  - This study was to analyze the infectious complications after hematopoietic stem
      cell transplantation (HSCT) according to the recent changes of HSCT. Medical
      records of 379 adult patients who underwent HSCT consecutively at Catholic HSCT
      Center from January 2001 to December 2002 were reviewed retrospectively.
      Allogeneic HSCT accounted for 75.7% (287/379) and autologous HSCT for 24.3%
      (92/379). During pre-engraftment period, bacterial infection was predominant, and
      E. coli was still the most common organism. After engraftment, viral infection
      was predominant. The incidence of invasive fungal infection showed bimodal
      distribution with peak correlated with neutropenia and graft-versus-host disease
      (GVHD). The overall mortality and infection-related mortality rates according to
      3 periods were as follows; during pre-engraftment, 3.16% (12/379) and 1.8%
      (7/379); during midrecovery period, 7.9% (29/367) and 4.1% (15/367); during late
      recovery period, 26.9% (91/338), and 15.9% (54/338). Risk factors for infection
      related mortality were as follows; during pre-engraftment period, fungal
      infection and septic shock; during the mid-recovery period, hemorrhagic cystitis
      and delayed engraftment; during the late-recovery period, fungal infection,
      chronic GVHD, and relapse. In conclusion, infection was still one of the main
      complications after HSCT and highly contributes to mortality. The early diagnosis
      and the effective vaccination strategy are needed for control of infections.

PMID- 16614502
TI  - Insertion/deletion polymorphism of angiotensin converting enzyme gene in Kawasaki
      disease.
AB  - Polymorphism of angiotensin converting enzyme (ACE) gene is reported to be
      associated with ischemic heart disease, hypertrophic cardiomyopathy, and
      idiopathic dilated cardiomyopathy. In this study, we investigated the
      relationship between Kawasaki disease and insertion/deletion polymorphism of ACE
      gene. Fifty five Kawasaki disease patients and 43 healthy children were enrolled.
      ACE genotype was evaluated from each of the subjects' DNA fragments through
      polymerase chain reaction (PCR). Frequencies of ACE genotypes (DD, ID, II) were
      12.7%, 60.0%, 27.3% in Kawasaki group, and 41.9%, 30.2%, 27.9% in control group
      respectively, indicating low rate of DD and high rate of ID genotype among
      Kawasaki patients (p<0.01). Comparing allelic (I, D) frequencies, I allele was
      more prevalent in Kawasaki group than in control group (57.3% vs. 43.0%, p<0.05).
      In Kawasaki group, both genotype and allelic frequencies were not statistically
      different between those with coronary dilatations and those without. ACE gene I/D
      polymorphism is thought to be associated with Kawasaki disease but not with the
      development of coronary dilatations.

PMID- 16614503
TI  - The effect of insulin resistance on prognosis of non-diabetic patients who
      underwent percutaneous coronary intervention.
AB  - Insulin resistance is an important risk factor for coronary artery disease.
      However, there has been no data regarding its clinical effect on the outcomes of
      percutaneous coronary intervention (PCI) in non-diabetic patients. We analyzed 98
      non-diabetic consecutive patients (59+/-11.5 yr, male:female=63:35) who underwent
      elective coronary angiography. The patients were divided into two groups: Group I
      (n=71; the value of HOMA-IR [homeostasis model assessment of insulin resistance]
      <2.6) and Group II (n=27; the value of HOMA-IR > or = 2.6). In-hospital and 30
      day major adverse cardiac events (MACE) were compared between the two groups. The
      concentrations of fasting insulin and triglyceride were significantly higher in
      Group II than in Group I. Significant correlations were observed between the
      value of HOMA-IR and body mass index (r=0.489, p<0.001), levels of total
      cholesterol (r=0.204, p=0.045), triglyceride (r=0.334, p=0.001) and
      apolipoprotein B (r=0.212, p=0.038). PCI was performed in 59 patients (60.2%). In
      hospital and 30-day MACE were higher in Group II than Group I (2.4% vs. 27.8%,
      p=0.008; 2.4% vs. 27.8%, p=0.008). Multivariate analysis revealed that the value
      of HOMA-IR > or = 2.6 was an independent predictor of MACE. Increased HOMA-IR
      level is an important prognostic indicator in non-diabetic patients underwent
      PCI.

PMID- 16614504
TI  - Acute geometric changes of the mitral annulus after coronary occlusion: a real
      time 3D echocardiographic study.
AB  - We performed real-time 3D echocardiography in sixteen sheep to compare acute
      geometric changes in the mitral annulus after left anterior descending coronary
      artery (LAD, n=8) ligation and those after left circumflex coronary artery (LCX,
      n=8) ligation. The mitral regurgitation (MR) was quantified by regurgitant volume
      (RV) using the proximal isovelocity surface area method. The mitral annulus was
      reconstructed through the hinge points of the annulus traced on 9 rotational
      apical planes (angle increment=20 degrees). Mitral annular area (MAA) and the
      ratio of antero-posterior (AP) to commissure-commissure (CC) dimension of the
      annulus were calculated. Non-planar angle (NPA) representing non-planarity of the
      annulus was measured. After LCX occlusion, there were significant increases of
      the MAA during both early and late systole (p<0.01) with significant MR (RV: 30+/
      14 mL), while there was neither a significant increase of MAA, nor a significant
      MR (RV: 4+/-5 mL) after LAD occlusion. AP/CC ratio (p<0.01) and NPA (p<0.01) also
      significantly increased after LCX occlusion during both early and late systole.
      The mitral annulus was significantly enlarged in the antero-posterior direction
      with significant decrease of non-planarity compared to LAD occlusion immediately
      after LCX occlusion.

PMID- 16614505
TI  - Surgical resection of recurrent lung cancer in patients following curative
      resection.
AB  - We reviewed our experience with resection of recurrent lung cancer to evaluate
      the benefit and risk of the procedure. From December 1994 to December 2003, 29
      consecutive patients underwent pulmonary resections for recurrent lung cancer.
      The mean duration from the first resection to second surgery was 25.4+/-15.1
      months for the definite 2nd primary lung cancer (n=20) and 8.9+/-5.7 months for
      metastatic lung cancer (n=9). The procedures at the second operations were
      completion-pneumonectomy in 11 patients, lobectomy in 5 patients, wedge resection
      in 12 patients and resection and anastomosis of trachea in 1 patient. Morbidity
      was observed in 6 (21%) of the patients and the in-hospital mortality was two
      patients (7%) after the repeated lung resection. Tumor recurrence after
      reoperation was observed in 14 patients (48%). The actuarial 5-yr survival rate
      was 69% and the 5-yr disease free rate following reoperation was 44%. No
      significant difference was found in overall survival and disease free survival
      between the 2nd primary lung cancer group and the metastatic lung cancer group.
      The recurrence rate following reoperation was significantly different between the
      wedge resection group and lobectomy/completion pneumonectomy group (p=0.008), but
      the survival rate was not significantly different (p=0.41). Surgical intervention
      for recurrent lung cancers can be performed with acceptable mortality and
      morbidity. If tolerable, completion pneumonectomy or lobectomy is recommended for
      resection of recurrent lung cancer.

PMID- 16614506
TI  - Preoperative concurrent radiochemotherapy and surgery for stage IIIA non-small
      cell lung cancer.
AB  - This is to examine whether aggressive multimodality therapy improves the
      treatment outcomes in stage IIIA non-small cell lung cancer (NSCLC). Fifty-three
      consecutive NSCLC patients with N2 disease, confirmed by mediastinoscopic biopsy,
      received preoperative thoracic radiation therapy (45 Gy/5 weeks) concurrent with
      two cycles of oral etoposide and intravenous cisplatin and surgery. Postoperative
      radiation therapy (PORT, 18 Gy/2 weeks) was optionally recommended for those with
      the risk factors of loco-regional recurrence based on the surgical and
      pathological findings. Surgical resection was performed in 38 patients (71.7%),
      and down-staging was achieved in 19 patients (50%). The median survival period
      was 27 months in 38 patients who underwent resection, and the rates at 3-yr of
      overall survival, loco-regional control, distant metastasis-free survival, and
      disease-free survival were 44.3%, 87.9%, 32.9%, and 29.3%. Significantly
      favorable factor regarding overall survival was achieving p0/I stage by the
      multivariate analysis. PORT was successful in reducing locoregional recurrences
      in patients with the risk factors. Current preoperative concurrent
      radiochemotherapy and surgery by the authors resulted in comparable survival with
      other reports, however, further refinement of multimodality approach may be
      warranted for more effective reduction of distant metastasis.

PMID- 16614507
TI  - Surgical treatment of non-small cell lung cancer with isolated synchronous brain
      metastases.
AB  - This study is a retrospective examination of our experiences with patients who
      underwent treatment of isolated synchronous brain metastases coupled with primary
      non-small cell lung cancer. From January 1995 to June 2004, 12 patients presented
      with isolated synchronous brain metastases coupled with primary non-small cell
      lung cancer. The patient was comprised of 8 men and 4 women. The median age was
      52 yr, in a range of 32 to 75 yr. Median follow-up duration was 10.6 months, in a
      range of 2 to 55.8 months. Recurrence developed in 7 patients, and the median
      interval from 1st treatment to recurrence was 4.5 months (2.8-6.5 months). The
      overall 1-yr survival rate was 61.7%. The 1-yr survival rates for pathologic N0
      and N1 cases were 75% and 66.7%, respectively. The median survival duration for
      pathologic N2 was 6.2 months (95% CI, 4.8-7.5 months). The 1-yr survival rate for
      cases of single brain metastasis was 75%. Based on our current observations, we
      could speculate that aggressive management of primary non-small cell lung cancer
      and isolated synchronous brain metastases was beneficial in a selected group of
      patients, as long as the brain lesions and pulmonary lesions were limited or
      resectable.

PMID- 16614508
TI  - Detection of pre-invasive endobronchial tumors with D-light/autofluorescence
      system.
AB  - Autofluorescence bronchoscopy (AFB) is one of the newly developed diagnostic
      tools to detect the pre-cancerous lesions in the bronchial tissue. The utility of
      DLight/AFB in the detection of pre-cancerous lesions was compared to the standard
      white light bronchoscopy (WLB). In 113 patients (male 106, female 7), who visited
      hospital for evaluation of lung cancer, WLB and AFB were done and 364 biopsy
      specimens were obtained from November 2001 to August 2002. The bronchoscopic
      findings on WLB and AFB were compared to the pathological findings. The
      pathologic diagnoses of the specimens were as follows: normal in 96; hyperplasia
      in 69; metaplasia in 32; mild dysplasia in 13, moderate dysplasia in 6, severe
      dysplasia in 4; carcinoma in situ in 6; invasive carcinoma in 57. The relative
      sensitivity of adjunctive AFB to WLB vs. WLB alone was 1.5 in moderate dysplasia
      or worse lesions, and 3.2 in intraepithelial neoplasia. The specificity of
      adjunctive AFB and WLB alone were 0.91 and 0.5, respectively. The adjunctive AFB
      to the standard WLB increased the detection rate of the localized pre-invasive
      lesions. However, there was high rate of false positive in AFB.

PMID- 16614509
TI  - Association between sensitization to outdoor spider mites and clinical
      manifestations of asthma and rhinitis in the general population of adults.
AB  - It has been demonstrated that spider mites such as the two-spotted spider mite
      (Tetranychus urticae) are important allergens for fruit farmers. A total of 2,467
      adults (795 metropolitan urban, 788 non-metropolitan urban, and 884 rural
      subjects) were enrolled. They responded to the questionnaire, and underwent
      methacholine bronchial provocation tests as well as skin prick tests to locally
      common aeroallergens including the two-spotted spider mite. The prevalences of
      asthma and rhinitis as reported on the questionnaire were 7.8% and 16.4% of
      adults aged 20-35, 9.4% and 24.7% of those 36-50, and 17.7% and 21.7% of those
      older than 50, respectively. Among the older group, the two-spotted spider mite
      was the most common sensitizing allergen, although it was second of that of house
      dust mites among the other two age groups. Sensitization to the two-spotted
      spider mite was significantly associated with the prevalence of asthma and
      rhinitis among the younger age group, and associated with the prevalence of
      rhinitis among the older age group. The two-spotted spider mite might be a common
      sensitizing allergen in the general population of adults, and sensitization to
      this mite may play a role in the manifestation of asthma and rhinitis symptoms
      during adulthood.

PMID- 16614510
TI  - Prognostic significance of multidrug resistance gene 1 (MDR1), multidrug
      resistance-related protein (MRP) and lung resistance protein (LRP) mRNA
      expression in acute leukemia.
AB  - The prognostic significance of multidrug resistance (MDR) gene expression is
      controversial. We investigated whether multidrug resistance gene 1 (MDR1),
      multidrug resistance-related protein (MRP) and lung resistance protein (LRP) mRNA
      expression are associated with outcomes in acute leukemia patients. At diagnosis
      we examined MDR1, MRP and LRP mRNA expression in bone marrow samples from 71
      acute leukemia patients (39 myeloid, 32 lymphoblastic) using nested RT-PCR. The
      expression of each of these genes was then expressed as a ratio in relation to
      beta-actin gene expression, and the three genes were categorized as being either
      0, 1+, 2+ or 3+. MDR1, MRP and LRP mRNA expression was detected in 23.9%, 83.1%
      and 45.1 %, respectively. LRP mRNA expression was significantly associated with
      resistance to induction chemotherapy in acute leukemia patients, and in the AML
      proportion (p=0.02 and p=0.03, respectively). MRP and high MDR1 mRNA expression
      was associated with poorer 2-yr survival (p=0.049 and p=0.04, respectively).
      Patients expressing both MRP and LRP mRNA had poorer outcomes and had worse 2-yr
      survival. The present data suggest that MDR expression affects complete remission
      and survival rates in acute leukemia patients. Thus, determination of MDR gene
      expression at diagnosis appears likely to provide useful prognostic information
      for acute leukemia patients.

PMID- 16614511
TI  - Clinical characteristics and outcomes of posttransplant lymphoproliferative
      disorders following allogeneic hematopoietic stem cell transplantation in Korea.
AB  - Between 1995 and 2003, seven cases of posttransplant lymphoproliferative disorder
      (PTLD) were identified among 1,116 patients who received allogeneic hematopoietic
      stem cell transplantations (HSCT) at Catholic HSCT Center (overall incidence
      0.6%). Five (71.4%) patients had episodes of acute graft-versus-host-disease
      (GVHD) and were treated with steroids. Cervical lymphadenopathy was observed in
      most cases (71.4%), but clinical symptoms varied depending on the involved sites.
      Pathologic findings varied: 1 case of plasmacytic hyperplasia, 3 of polymorphic
      PTLD, 2 of diffuse large B-cell lymphoma, 1 of large T-cell lymphoma, which
      proved to be associated with Epstein-Barr virus (EBV). The proportion of EBV
      negative PTLD was 33.3%. Five patients demonstrated a good response to treatment
      (treatment response rate 71.4%). The overall mortality was 42.8%, and one death
      was directly attributable to PTLD. The incidence of PTLD is expected to increase,
      based on the rising use of grafts from alternative donors and recent clinical
      features of PTLD manifested by a disseminated and fulminant nature. It is
      necessary to have a high level of suspicion when monitoring patients and readily
      adopt prompt and effective cellular immunotherapy for PTLD.

PMID- 16614512
TI  - Churg-Strauss syndrome: the clinical features and long-term follow-up of 17
      patients.
AB  - Churg-Strauss syndrome (CSS) is a rare multi-system vasculitis; some cases have
      been reported in Korea. The aim of this study is to describe the clinical
      features, treatment outcome, and long-term follow-up of CSS from a single Korean
      medical center. Between 1995 and 2004, seventeen patients were diagnosed with CSS
      at the Department of Medicine of the Samsung Medical Center, Sungkyunkwan
      University School of Medicine. The diagnosis of CSS is based on the
      classification criteria of the American Collage of Rheumatology. All patients had
      asthma. As in other case series, the lung, peripheral nervous system, and skin
      were the most commonly involved organs. During the active stage of the disease,
      most of the patients exhibited peripheral blood eosinophilia and an elevated
      serum eosinophil cationic protein level. Ten patients were treated with pulses of
      methylprednisolone followed by tapering and cyclophosphamide, and the others were
      treated with corticosteroids alone. The outcomes after long-term follow-up were
      generally good. One patient who was refractory to initial treatment died of heart
      failure during the follow-up period. CSS was highly variable in its presentation
      and course. The manifestations may range from mild symptoms to life-threatening
      conditions. The outcome after long-term follow-up was as good as that of previous
      studies.

PMID- 16614513
TI  - Expression of angiopoietin 1, 2 and their common receptor Tie2 in human gastric
      carcinoma: implication for angiogenesis.
AB  - Angiogenesis, formation of new microvessels providing oxygen and nutrient supply,
      is essential for tumor growth. It is dependent on the production of angiogenic
      growth factors by tumor cells. Angiopoietin 1 (Ang-1) and 2 (Ang-2) and their
      common receptor, Tie2, are thought to be critical regulators of tumor
      angiogenesis. We examined expression of Ang-1, Ang-2, and their common receptor
      Tie2 mRNAs and proteins in gastric cancers using in situ hybridization and
      immunohistochemistry. We also investigated the relationship between their
      expression and differentiation of cancer cells, lymph node metastasis, tumor
      size, depth of cancer cell invasion, TNM staging and microvessel density (MVD).
      The expression of Ang-1, Ang-2, and Tie2 mRNA in cancer cells significantly
      correlated with the MVD (p<0.001, <0.001 and =0.019, respectively). Ang-1 and
      Tie2 positivity correlated with advanced gastric cancers (p<0.05) and larger
      cancers had higher positive rates of Ang-1, Ang-2, and Tie2 mRNA expression
      (p<0.001, =0.010 and =0.039, respectively). Significant positive correlations
      were also found between mRNA expression of Tie2 and those of Ang-1 and Ang-2
      (p<0.01 and <0.001, respectively). These findings indicate that the expression of
      Ang-1 and Ang-2 is important for tumor angiogenesis, and suggest a possible role
      of autocrine/paracrine function of angiopoietin/Tie2 system in gastric cancer
      progression.

PMID- 16614514
TI  - The degrees of hepatocyte cytoplasmic expression of hepatitis B core antigen
      correlate with histologic activity of liver disease in the young patients with
      chronic hepatitis B infection.
AB  - Subcellular localizaton of HBcAg have been found to be related to the activity of
      liver disease and HBV replication. The aim of this study was to determine whether
      the degree of expression of HBcAg in the hepatocyte nucleus and cytoplasm
      reflects the level of viral replication and histological activity in chronic HBV
      infection. A total of 102 patients with biopsy proven chronic hepatitis B were
      included. There was a highly significant correlation between the levels of HBV
      DNA in serum and the degree of expression of HBcAg in the nucleus for HBeAg
      positive(p=0.000) and negative patients(p=0.04). There was a highly significant,
      correlation between the degrees of expression of HBcAg in hepatocyte cytoplasm
      and histologic activities (p<0.01) for HBeAg-positive patients. The degrees of
      expression of HBcAg in the hepatocyte cytoplasm correlated positively with the
      lobular activities (p<0.01), but not correlated with the portal activity and
      fibrosis for HBeAg-negative patients. In conclusion, in the young patients with
      chronic B viral hepatitis, the degree of expression of HBcAg in the hepatocyte
      nucleus may affect viral load, and the degree of expression of HBcAg in the
      hepatocyte cytoplasm may affect histologic activities of liver disease.

PMID- 16614515
TI  - The impact of intima-media thickness of radial artery on early failure of
      radiocephalic arteriovenous fistula in hemodialysis patients.
AB  - This study was performed to investigate the impact of intima-media thickness
      (IMT) of radial artery on early failure of radiocephalic arteriovenous fistula
      (AVF) in hemodialysis (HD) patients. Ninety uremic patients undergoing
      radiocephalic AVF operation were included in this study. During the operation, 10
      mm long partial arterial walls were removed with elliptical form for microscopic
      analysis. Specimens were stained with trichrome and examined by a pathologist
      blinded to the clinical data. And then AVF patency was followed up for 1 yr after
      the operation. Of the total 90 patients, 31 patients (34%) had AVF failure within
      1 yr after the operation. Mean IMT was thicker in failed group (n=31) than in
      patent group (n=59) (486+/-130 micrometer vs. 398+/-130 micrometer, p=0.004). The
      AVF patency rate within 1 yr after the operation was lower in patients with IMT >
      or = 500 micrometer (n=26) than in patients with IMT <500 micrometer (n=64)
      (p=0.017). Age was an independent risk factor of IMT. Diabetes mellitus tended to
      be independent risk factor but not statistically significant. Our data suggest
      that increased radial artery IMT is closely associated with early failure of
      radiocephalic AVF in HD patients.

PMID- 16614516
TI  - Influence of blood lead concentration on the nerve conduction velocity in
      patients with end-stage renal disease.
AB  - Diseases of the peripheral nervous system are the most prevalent in patients with
      end-stage renal disease (ESRD). Although increased blood levels of lead in ESRD
      have been reported, the role of lead remains to be elucidated. The purpose of
      this study was to determine the connection of blood lead concentration with
      peripheral nerve conduction velocity. One hundred ninety-eight healthy subjects
      (control group) and 68 patients with ESRD undergoing hemodialysis (ESRD group)
      were enrolled. Nerve conduction was measured within two hours after hemodialysis.
      Orthodromic sensory nerve action potentials and compound muscle action potentials
      were recorded on the median, ulnar, and radial nerves. Hemoglobin-corrected blood
      lead was significantly higher in ESRD patients than in controls (9.1+/-2.8
      microgram/dL vs. 5.9+/-2.3 microgram/dL, p<0.001). 32.4% of 68 ESRD patients with
      diabetes mellitus were significantly related to poorer motor and sensory nerve
      conduction velocity (p<0.001). However, blood lead was not a significant
      predictor of the nerve conduction velocity (p>0.05). Our result suggested that
      even though the blood lead levels were high in ESRD, they were not associated
      with the decline of peripheral nerve function. Diabetes mellitus is a primary
      independent risk of neuropathy in ESRD patients.

PMID- 16614517
TI  - The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scales in men with
      prostate cancer: reliability and validity of the Korean version.
AB  - The Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire is a
      relevant, worldwide tool used for assessing the health-related quality of life in
      men with prostate cancer. The purpose of this study was to translate the FACT-P
      into Korean, to assess its reliability and validity, and to test its
      discriminative ability between the cancer patients and normal controls. The
      Korean version was developed via the FACT multilingual translation project. The
      translated questionnaire was self-administered to 70 prostate cancer patients and
      70 age-matched controls. In evaluating its psychometric properties for cancer
      patients, internal consistency and test-retest reliability were used. Validity
      was estimated by using inter-subscale correlations and discriminant validity
      between cancer patients and controls. Cronbach's alpha coefficient for the
      individual subscales were 0.7 or greater (range 0.73 to 0.89), except for
      emotional well-being (0.61). The test-retest reliability showed high correlations
      (intraclass coefficients ranged from 0.72 to 0.93). Inter-subscale correlations
      demonstrated each subscale was unrelated, but moderate correlation was observed
      between social/family well-being and functional well-being subscales (r=0.56).
      The FACT-P scale could discriminate reliably between the cancer patients and
      controls in most subscales. In conclusion, the Korean version of the FACT-P is a
      reliable and valid questionnaire in patients with prostate cancer.

PMID- 16614518
TI  - Clinical efficacy of body mass index as predictor of in vitro fertilization and
      embryo transfer outcomes.
AB  - The aim of this study was to evaluate the clinical efficacy of body mass index
      (BMI) as a predictor of in vitro fertilization and embryo transfer (IVF-ET)
      outcomes. Two hundred twenty-three IVF-ET cycles in 164 patients under 37 yr
      using GnRH agonist long protocols were included in this retrospective study. All
      of the selected cases were divided into two groups by a cutoff of 24 kg/m2 and
      these two groups were compared in regard to the outcomes of IVF-ET. There were no
      significant differences between group 1 (BMI <24 kg/m2) and group 2 (BMI > or =
      24 kg/m2) in age, basal serum FSH level, estradiol (E2) level and endometrial
      thickness on hCG day, number of retrieved oocytes and transferred embryos.
      However, higher doses of gonadotropins were used in group 2 (30.8+/-12.7 ampoules
      vs. 35.4+/-15.3 ampoules, p=0.051). The clinical pregnancy rate was significantly
      lower in group 2 (25.9% vs. 10.5%, p=0.041) and implantation rate tended to be
      lower in group 2 (12.7% vs. 6.8%, p=0.085). BMI > or = 24 kg/m2 can be a
      candidate prognosticator of IVF-ET outcomes.

PMID- 16614519
TI  - The effect of Vero cell coculture on the development of mouse embryos exposed to
      monoclonal antibodies specific for mammalian heat shock protein 60.
AB  - Heat shock proteins (HSP) have been identified as an important factor of a very
      complex and highly conserved cellular defense mechanism to preserve cell survival
      under adverse environmental conditions. HSP 60 are immunodominant antigens of
      microbe such as Chlamydia trachomatis and have a potentiality to become a target
      antigen due to antigenic similarity between chlamydial and human HSP. This study
      was conducted to investigate the effects of Vero cell coculture to anti-HSP 60 on
      the early mouse embryo development in vitro. The 2-cell mouse embryos (ICR) were
      cultured and mouse embryo development was observed every 24 hr for 3 days. 45%
      and 22.1% of the embryos cultured in Ham's F-10 plus anti HSP 60 with Vero cells
      developed to the 4- to 8- cell stage (day 1) and morular stage (day 2) as
      compared with 29.2% and 2.7% of those cultured without Vero cells respectively.
      But at day 3, the beneficial effect of Vero cells was not noted. These findings
      suggest that Vero cells have some roles to overcome the detrimental effect of
      anti-HSP 60 to some degree. These results suggest that Vero cells coculture will
      promote reproductive outcome in patient previously sensitized to microbial (e.g.
      Chlamydia trachomatis) HSP 60.

PMID- 16614520
TI  - Clinicopathological significance of maspin expression in breast cancer.
AB  - Maspin is a unique serine proteinase inhibitor that has tumor suppressor
      activity. It has been reported that maspin is expressed in normal human mammary
      epithelial cells and it is down-regulated during the progression of cancer.
      However, to date, there is very limited data on the clinical significance of
      maspin expression in human breast cancer. In this study, maspin expression was
      assessed immunohistochemically from 80 invasive ductal carcinoma (IDC) specimens
      of the breast. Also, maspin expression was compared with the clinicopathological
      factors (age, grade, tumor size and lymph node status), the expression of
      estrogen receptor (ER), progesterone receptor (PR) and p53, DNA ploidy and the
      overall survival in an attempt to assess its prognostic value. The maspin
      expression was positive in 25 IDC cases (31.3%). The maspin expression in IDC was
      significantly correlated with a higher histologic grade, a larger tumor size, a
      positive p53 status and shorter survival. There was an inverse association with
      maspin expression and the PR status. These findings suggest that maspin
      expression is not down-regulated with the progression of cancer and maspin
      expression may be associated with a poor prognosis. The immunohistochemical
      detection of maspin in breast cancers may be helpful for predicting an aggressive
      phenotype.

PMID- 16614521
TI  - Role of staphylococcal superantigen in atopic dermatitis: influence on
      keratinocytes.
AB  - Staphylococcus aureus may perform an crucial function in atopic dermatitis (AD),
      via the secretion of superantigens, including staphylococcal enterotoxins (SE) A
      or B, and toxic shock syndrome toxin-1 (TSST-1). Dysregulated cytokine production
      by keratinocytes (KCs) upon exposure to staphylococcal superantigens (SsAgs) may
      be principally involved in the pathophysiology of AD. We hypothesized that
      lesional KCs from AD may react differently to SsAgs compared to nonlesional skin
      or normal skin from nonatopics. We conducted a comparison of HLA-DR or CD1a
      expression in lesional skin as opposed to that in nonlesional or normal skin by
      immunohistochemistry (IHC). We also compared, using ELISA, the levels of IL
      1alpha, IL-1beta, and TNF-alpha secreted by cultured KCs from lesional,
      nonlesional, and normal skin, after the addition of SEA, SEB and TSST-1. IHC
      revealed that both HLA-DR and CD1a expression increased significantly in the
      epidermis of lesional skin versus nonlesional or normal skin in quite a similar
      manner. IL-1alpha, IL-1beta, and TNF-alpha secretion was also significantly
      elevated in the cultured KCs from lesional skin after the addition of SsAgs. Our
      results indicated that KCs from lesional skin appear to react differently to
      SsAgs and increased proinflammatory cytokine production in response to SsAgs may
      contribute to the pathogenesis of AD.

PMID- 16614522
TI  - A novel application of amniotic membrane in patients with bullous keratopathy.
AB  - To evaluate the efficacy of amniotic membrane in the management of painful
      bullous keratopathy secondary to the intractable glaucoma and in preventing
      exposure of drainage devices, we inserted Ahmed valve with amniotic membrane
      patch graft over the implant itself, and debrided corneal epithelium with
      amniotic membrane graft over the exposed stroma as a single operation. During the
      follow-up periods, we monitored vision, intraocular pressure (IOP), presence of
      ocular pain, and postoperative complications associated with the implants. The
      mean follow up period was 8.4+/-3.2 months. IOP was well controlled after the
      intervention. The preoperative mean IOP was measured as 43.9+/-9.0 mmHg and
      lowered to 16.1+/-1.8 mmHg at the last visit and no complications associated with
      the implants were noted. Even though the improvement in vision was not prominent,
      the ocular surface stabilized rapidly and ocular pain associated with bullous
      keratopathy disappeared soon after surgery. Conclusively the use of amniotic
      membrane in conjunction with Ahmed valve implantation is an effective way to
      relieve ocular pain and lessen the chances of complications associated with the
      implant in patients with intractable glaucoma and bullous keratopathy.

PMID- 16614523
TI  - Angiotensin-converting enzyme gene insertion/deletion polymorphism in Korean
      patients with systemic sclerosis.
AB  - To determine whether angiotensin-converting enzyme (ACE) gene insertion/deletion
      (I/D) polymorphism is associated with the development and clinical features of
      systemic sclerosis (SSc) in Korean, we studied seventy two Korean patients with
      SSc fulfilling the ACR preliminary classification criteria. The controls were 114
      healthy, disease free Koreans. ACE I/D genotypes were determined by PCR method
      using oligonucleotides. Sixty eight patients (94.4%) were women and age at
      diagnosis was 43.5+/-12.6 yr old (mean+/-SD). Thirty nine patients (54.2%) had a
      diffuse type of SSc. There were no statistical differences in the frequencies of
      all ACE I/D genotypes and D allele between patients and controls, and neither
      between diffuse and limited types of SSc. ACE I/D gene polymorphism was not
      associated with the development of SSc in Korea. The investigation for the
      pathogenesis of SSc requires more studies about the role of other candidate genes
      such as endothelin, TGF-beta, nitric oxide, or angiotensin II receptor in
      addition to the ACE genes.

PMID- 16614524
TI  - Therapeutic factors of cognitive behavioral group treatment for social phobia.
AB  - This study investigated the therapeutic factors influencing the outcome of
      cognitive behavioral group treatment for social phobia and the most helpful
      therapeutic component. Fifty psychiatric outpatients who were diagnosed with
      social phobia according to the DSM-IV criteria were chosen as subjects. Patients
      were asked to complete the Yalom's Curative Factors Questionnaire and Therapeutic
      Components Evaluation Form at the end of their Cognitive Behavioral Group
      Treatment (CBGT). The patients who showed more improvement rated significantly
      higher in therapeutic factors such as "Interpersonal learning-output",
      "Guidance", "Universality", "Group cohesiveness" than the patients who showed
      less improvement. Among the four components of CBGT for social phobia, cognitive
      restructuring was rated as most helpful. These results suggest which therapeutic
      factors and components should be highlighted in CBGT for social phobia.

PMID- 16614526
TI  - Evaluation of morphological plasticity in the cerebella of basketball players
      with MRI.
AB  - Cerebellum is a key structure involved in motor learning and coordination. In
      animal models, motor skill learning increased the volume of molecular layer and
      the number of synapses on Purkinje cells in the cerebellar cortex. The aim of
      this study is to investigate whether the analogous change of cerebellar volume
      occurs in human population who learn specialized motor skills and practice them
      intensively for a long time. Magnetic resonance image (MRI)-based cerebellar
      volumetry was performed in basketball players and matched controls with V-works
      image software. Total brain volume, absolute and relative cerebellar volumes were
      compared between two groups. There was no significant group difference in the
      total brain volume, the absolute and the relative cerebellar volume. Thus we
      could not detect structural change in the cerebellum of this athlete group in the
      macroscopic level.

PMID- 16614525
TI  - Neuroprotective effect of cycloheximide on hypoxic-ischemic brain injury in
      neonatal rats.
AB  - This study was done to determine the neuroprotective effect of cycloheximide on
      neonatal hypoxic-ischemic brain injury. Seven day-old newborn rat pups were
      subjected to 90 min of 8% oxygen following a unilateral carotid artery ligation.
      The extent of cerebral infarction was evaluated at 1 and 4 week of recovery.
      Apoptosis was identified by performing terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a
      combination of fluoresceinated annexin V and propidium iodide. Brain infarction
      area was significantly increased at 4 week compared to 1 week after hypoxia
      ischemia in the control group. With cycloheximide treatment, the number of TUNEL
      positive cells in the ipsilateral cerebral cortex at 48 hr and peri-infarct area
      at 1 and 4 week of recovery was significantly reduced, both apoptotic and
      necrotic cells by flow cytometry 48 hr after the injury were significantly
      reduced, and the extent of cerebral infarction at 1 and 4 week of recovery was
      also significantly attenuated compared to the hypoxia-ischemia control group. In
      summary, our data suggest that apoptosis plays an important role in the
      development of delayed infarction, and inhibition of apoptosis with cycloheximide
      significantly reduces the ensuing cerebral infarction in a newborn rat pup model
      of cerebral hypoxia-ischemia.

PMID- 16614527
TI  - Outbreak of late-onset group B streptococcal infections in healthy newborn
      infants after discharge from a maternity hospital: a case report.
AB  - During a four-week period, four healthy term newborn infants born at a regional
      maternity hospital in Korea developed late-onset neonatal group B Streptococcus
      (GBS) infections, after being discharged from the same nursery. More than 10 days
      after their discharge, all of the infants developed fever, lethargy, and poor
      feeding behavior, and were subsequently admitted to the Korea University Medical
      Center, Ansan Hospital. GBS was isolated from the blood cultures of three babies;
      furthermore, GBS was isolated from 2 cerebral spinal fluid cultures. Three babies
      had meningitis, and GBS was isolated from their cerebral spinal fluid cultures.
      This outbreak was believed to reflect delayed infection after early colonization,
      originating from nosocomial sources within the hospital environment. This report
      underlines the necessity for Korean obstetricians and pediatricians to be aware
      of the risk of nosocomial transmissions of GBS infection in the delivery room
      and/or the nursery.

PMID- 16614528
TI  - A case of neonatal alloimmune neutropenia associated with anti-human neutrophil
      antigen-1a (HNA-1a) antibody.
AB  - Neonatal alloimmune neutropenia (NAN) is an uncommon disease of the newborn
      provoked by the maternal production of neutrophil-specific alloantibodies,
      whereby neutrophil IgG antibodies cross the placenta and induce the destruction
      of fetal neutrophils. Affected newborns are usually identified by the occurrence
      of bacterial infections. The most frequent antigens involved in NAN are the human
      neutrophil antigen-1a (HNA-1a), HNA-1b, and HNA-2a. We report a neonate who was
      delivered at 36 weeks and had a severe neutropenia but who responded well to
      recombinant human granulocyte colony-stimulating factor (rhG-CSF). Anti-HNA-1a
      antibody was identified by mixed passive hemagglutination assay in both the sera
      of the baby and the mother. The baby had HNA-1a and HNA-1b but the mother had
      only HNA-1b on granulocytes. This is the first Korean report of NAN in which the
      specificity of the causative antibody was identified.

PMID- 16614529
TI  - Primary percutaneous coronary intervention for acute myocardial infarction with
      idiopathic thrombocytopenic purpura: a case report.
AB  - Acute myocardial infarction (AMI) is rare in patients with idiopathic
      thrombocytopenic purpura (ITP). We describe a case of an AMI during
      thrombocytopenia in a patient with chronic ITP. A 47-yr-old woman presented with
      anterior chest pain and a low platelet count (21,000/microliter) at admission.
      Urgent coronary angiography revealed total occlusion of proximal right coronary
      artery and primary percutaneous coronary intervention (PCI) was performed
      successfully. This case suggests that primary PCI may be a therapeutic option for
      an AMI in patients with ITP, even though the patient had severe thrombocytopenia.

PMID- 16614530
TI  - A case of santorinicele without pancreas divisum: diagnosis with multi-detector
      row computed tomography.
AB  - A santorinicele is defined as a focal cystic dilatation of the terminal portion
      of the dorsal pancreatic duct at the minor papilla. Most cases reported
      previously were associated with pancreas divisum and a santorinicele without
      pancreas divisum is known to be rare. We recently experienced a typical case of a
      santorinicele without pancreas divisum in a 67-yr-old woman with abdominal pain
      and hematochezia, subsequently proven to be the result of an ischemic colitis.
      The santorinicele was diagnosed incidentally with multi-detector row computed
      tomography using a minimum intensity projection technique, which clearly showed a
      cystic dilatation of the terminal portion of the dorsal pancreatic duct and a
      communication between the ventral and dorsal pancreatic ducts. This finding was
      also confirmed by a magnetic resonance cholangiopancreatography.

PMID- 16614531
TI  - Laparoscopic management of complicated urachal remnant in a child.
AB  - A few cases of laparoscopic surgery for urachal remnant in children has been
      reported in English literature. With recent developments in minimal invasive
      surgery, laparoscopic approach for urachal remnant in adulthood is recommended by
      some laparoscopic surgeons because of its technical feasibility and safety as
      well as cosmesis. Recently we experienced a case of complicated urachal remnant
      in a 14-month-old girl, who was managed by laparoscopic approach. At
      presentation, she complained of high fever and lower urinary tract symptoms.
      After 6 weeks of antibiotics therapy, laparoscopic surgery was performed
      transperitoneally via 3 ports. Our experience suggests that laparoscopic excision
      of urachal remnant can be performed easily and safely in children.

PMID- 16614532
TI  - A case of autoimmune hemolytic anemia associated with an ovarian teratoma.
AB  - Autoimmune hemolytic anemia associated with an ovarian teratoma is a very rare
      disease. However, treating teratoma is the only method to cure the hemolytic
      anemia, so it is necessary to include ovarian teratoma in the differential
      diagnosis of autoimmune hemolytic anemia. We report herein on a case of a young
      adult patient who had severe autoimmune hemolytic anemia that was induced by an
      ovarian teratoma. A 25-yr-old woman complained of general weakness and dizziness
      for 1 week. The hemoglobin level was 4.2 g/dL, and the direct and indirect
      antiglobulin tests were all positive. The abdominal computed tomography scan
      revealed a huge left ovarian mass, and this indicated a teratoma. She was
      refractory to corticosteroid therapy; however, after surgical resection of the
      ovarian mass, the hemoglobin level and the reticulocyte count were gradually
      normalized. The mass was well encapsulated and contained hair and teeth. She was
      diagnosed as having autoimmune hemolytic anemia associated with an ovarian
      teratoma. To the best of our knowledge, this is the first such a case to be
      reported in Korea.

PMID- 16614533
TI  - Two cases of melasma with unusual histopathologic findings.
AB  - We reported two cases of clinically typical melasma presenting with unusual
      histopathologic findings. In one case, the epidermal melanocytes were markedly
      increased in number and protruded into the dermis, and in the other case,
      increased epidermal pigmentation as well as dermal melanocytosis were found. We
      suggested that the various treatment modalities of melasma should be applied
      depend on its histopathologic finding.

PMID- 16614534
TI  - Cutaneous polyarteritis nodosa presented with digital gangrene: a case report.
AB  - Cutaneous polyarteritis nodosa (CPAN) is an uncommon form of vasculitis involving
      small and medium sized arteries of unknown etiology. The disease can be
      differentiated from polyarteritis nodosa by its limitation to the skin and lack
      of progression to visceral involvement. The characteristic manifestations are
      subcutaneous nodule, livedo reticularis, and ulceration, mostly localized on the
      lower extremity. Arthralgia, myalgia, peripheral neuropathy, and constitutional
      symptoms such as fever and malaise may also be present. We describe a 34-yr-old
      woman presented with severe ischemic change of the fingertip and subcutaneous
      nodules without systemic manifestations as an unusual initial manifestation of
      CPAN. Therapy with corticosteroid and alprostadil induce a moderate improvement
      of skin lesions. However, necrosis of the finger got worse and the finger was
      amputated.

PMID- 16614535
TI  - A case of Pfeiffer syndrome.
AB  - Pfeiffer Syndrome is as rare as Apert syndrome in the Western population. This
      condition is very rare in the Asian population and has not been previously
      reported in Korea. The authors report with a review of literature the case of a
      newborn baby with Pfeiffer syndrome, manifested by bicoronal craniosynostosis,
      broad thumbs, and big toes. The infant also had bilateral syndactyly of the
      fingers and toes, mild proptosis, choanal hypoplasia and maxillary hypoplasia.

PMID- 16614536
TI  - Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease
      patients.
AB  - Adjunction of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN)
      to levodopa/carbidopa (LD/CD) improves motor symptoms in patients with Parkinson
      disease (PD) by a prolonged elimination of LD. But it is not known whether EN
      addition influences gastric emptying and thus LD pharmacokinetics and
      pharmacodynamics. Objectives were to simultaneously determine plasma LD
      elimination, gastric emptying, and clinical response after a single intake of the
      same LD dosage as LD/CD--or as (LD/CD/EN) formulation on 2 consecutive days. In
      both groups, PD patients with delayed gastric emptying had significant lower LD
      plasma concentrations. Addition of EN did not influence gastric emptying but
      significantly improved motor response, which was not different for patients with
      delayed gastric emptying. However, with and without EN adjunction gastric
      emptying distinctly contributes to the variability of plasma LD bioavailability.
      This may impact LD delivery to the brain and thus motor response in PD patients.
      Therefore, fine tuning of LD application, which considers gastric emptying,
      becomes more and more essential in advanced PD stages with a reduced striatal
      neuronal dopamine capacity, which is responsible for maintenance of motor
      response in early PD patients.

PMID- 16614537
TI  - Vitamin B6 versus mianserin and placebo in acute neuroleptic-induced akathisia: a
      randomized, double-blind, controlled study.
AB  - Treatment strategies against acute neuroleptic-induced akathisia (NIA) include
      anticholinergic (antimuscarinic) agents, dopamine agonists, GABAergic agents,
      beta-blockers, benzodiazepines, and serotonin antagonists. However, many patients
      who have acute akathisia fail to respond. In previous studies, mianserin and
      vitamin B6 were found to be effective in the treatment of acute akathisia. The
      purpose of this study was to compare the efficacy of B(6), mianserin and placebo
      in the treatment of acute NIA. Sixty schizophrenia and schizoaffective inpatients
      who have NIA were randomly divided to receive vitamin B(6) 1,200 mg/d, mianserin
      15 mg/d, or placebo for 5 days, in a double-blind design. The Barnes Akathisia
      Rating Scale, Brief Psychiatric Rating Scale, and Clinical Global Impression were
      used to assess the severity of NIA and psychotic symptoms. The assessment was
      made at baseline and daily for the duration of the study. Compared with the
      placebo group, the vitamin B(6)-treated and mianserin-treated patients showed a
      significant improvement in the subjective (P < 0.0001), subjective distress (P <
      0.0001), and global (P < 0.0001) subscales. The objective subscale did not show
      significant positive results (P = 0.056), but there was a trend toward symptom
      amelioration in both groups. A reduction of at least 2 points on the Barnes
      Akathisia Rating Scale global subscale was noted in the vitamin B(6) group
      (13/23, 56%) as well as in the mianserin groups (13/20, 65%), and in only one
      patient in the placebo group (1/17, 6%; P < 0.0005). Our results indicate that
      high doses of B(6) and a low dose of mianserin may be a useful addition to
      current treatments of NIA. The efficacy of vitamin B(6) and mianserin suggests
      that the pathophysiology of acute NIA is heterogeneous with the various subtypes
      of acute NIA responding differently to the various pharmacological approaches.

PMID- 16614538
TI  - Conversion from sustained release carbidopa/levodopa to
      carbidopa/levodopa/entacapone (stalevo) in Parkinson disease patients.
AB  - OBJECTIVES: This study was performed to determine if conversion from sustained
      release carbidopa/levodopa (SR-CL) with or without entacapone to
      carbidopa/levodopa/entacapone (CLE; Stalevo) improves motor functioning and
      quality of life in Parkinson disease (PD) patients and to assess patient
      tolerance and drug preference. METHODS: PD patients reporting suboptimal symptom
      control with SR-CL were converted to CLE. The basic conversion was 1 SR-CL 25/100
      to 1 25/100/200 CLE and 1 SR-CL 50/200 to 1 37.5/150/200 CLE with additional
      changes as necessary. RESULTS: There were 62 patients with an average age of 68
      years and an average disease duration of 11 years. CLE was preferred by 42
      patients and SR-CL was preferred by 20 patients. In those that preferred CLE,
      Unified Parkinson Disease Rating Scale (UPDRS) mentation and motor subscores,
      Parkinson Disease Questionnaire-39 (PDQ-39) quality-of-life activities of daily
      living (ADL) and bodily discomfort subscores, and Epworth Sleepiness Scale (ESS)
      scores were significantly improved. There were no significant changes in any
      measures in the group that preferred SR-CL. Common adverse effects in the group
      that preferred CLE included nausea, vomiting, increased dyskinesia or off time,
      dizziness, and somnolence. The most common adverse events in the group preferring
      SR-CL were increased off time or dyskinesia, nausea, and vomiting. CONCLUSIONS: A
      majority of patients suboptimally controlled on SR-CL can be successfully
      converted to CLE with improvements in motor function, quality of life, and
      sleepiness. Older patients, with longer disease duration not previously exposed
      to entacapone, may better tolerate CLE after the addition of entacapone.

PMID- 16614539
TI  - Safety of high-dose naltrexone treatment: hepatic transaminase profiles among
      outpatients.
AB  - OBJECTIVES: This study was carried out to test the hypothesis that the hepatic
      safety profile of prolonged high-dose oral naltrexone (150 mg/d) is acceptable if
      over-the-counter analgesic use is restricted. METHODS: Data from 41 consecutive
      outpatients with impulse-control disorder receiving naltrexone therapy were
      analyzed. RESULTS: The mean treatment duration was 328 days and the mean
      naltrexone dose was 142 mg/d. Pretherapy/posttherapy mean aspartate transaminase
      and alanine transaminase levels in the naltrexone-alone group were 21.79/22.54
      and 21.74/21.49 U, respectively (all within reference range). CONCLUSIONS:
      Although limited in scope, these findings support the hypothesis that long-term
      use of high-dose oral naltrexone is safe in otherwise healthy patients with
      impulse-control disorders who restrict their intake of acetaminophen, aspirin, or
      nonaspirin nonsteroidal anti-inflammatory drugs (NSAID). However, confirming
      studies are needed.

PMID- 16614541
TI  - Vasopressin antagonism: potential impact on neurologic disease.
AB  - Hyponatremia is a common electrolyte disorder frequently associated with central
      nervous system (CNS) diseases, neurosurgical procedures, and the use of
      neurotropic drugs. The clinical manifestations of hyponatremia are attributable
      to an increase in brain water content that occurs in response to a decrease in
      serum osmolality. Hyponatremia triggers adaptive processes in the brain to limit
      this cerebral swelling, but a rapid fall in serum [Na(+)] may overwhelm this
      adaptive mechanism. Patients with hyponatremia for more than 48 hours are at risk
      for developing osmotic demyelination when overly rapid correction of hyponatremia
      restores serum osmolality before this adaptive process can be reversed. The
      infusion of hypertonic saline for the restoration of serum [Na(+)] should
      therefore be carefully controlled to avoid this potentially devastating
      complication. Other options currently available for the treatment of
      hyponatremia, including strict restriction of fluid intake, are limited by their
      inconsistent response, poor tolerability, and frequent adverse effects. Arginine
      vasopressin (AVP)-receptor antagonists promote aquaresis (electrolyte-sparing
      excretion of free water) by blocking the antidiuretic action of the hormone at
      the level of the collecting ducts. In clinical trials, AVP-receptor antagonists
      increased serum [Na] in patients with euvolemic or hypervolemic hyponatremia
      associated with various conditions, including syndrome of inappropriate
      antidiuretic hormone secretion (SIADH). Patients who have neurologic disease with
      SIADH-related hyponatremia may be good candidates for treatment with AVP-receptor
      antagonists. Careful assessment of intravascular volume status before initiation
      of therapy and strict monitoring of the serum [Na] during treatment are necessary
      to avoid complications.

PMID- 16614540
TI  - Lisuride, a dopamine receptor agonist with 5-HT2B receptor antagonist properties:
      absence of cardiac valvulopathy adverse drug reaction reports supports the
      concept of a crucial role for 5-HT2B receptor agonism in cardiac valvular
      fibrosis.
AB  - OBJECTIVES: The high incidence of fibrotic cardiac valvulopathies reported in
      association with the 8beta-ergoline dopamine (DA) agonist, pergolide, and also
      case reports for cabergoline and bromocriptine have made it necessary to review
      the theoretical basis and actual findings in the case of another DA agonist, the
      8alpha-ergoline lisuride (used since the 1970s for migraine prophylaxis as well
      as since the 1980s for its prolactin-lowering and anti-Parkinson activity).
      METHODS: We have reviewed the pharmacology of lisuride in relation to other DA
      agonists, and we have performed a throughout literature search as well as a
      search of our own and other adverse drug reaction databases for a possible
      relationship of lisuride with cardiac valvulopathy or for any reports of fibrosis
      in other locations. RESULTS: Our review of the pharmacology and the literature
      strongly suggests that drug-induced cardiac valvulopathies are always related to
      a stimulatory drug effect on trophic 5-HT(2B) receptors. As lisuride is devoid of
      such an effect, but on the contrary is an extremely potent 5-HT(2B) antagonist,
      an association of lisuride therapy with cardiac valvulopathies seems to be highly
      unlikely. In agreement with this hypothesis, not a single report of a cardiac
      valvulopathy associated with lisuride therapy has been identified in any database
      so far.Furthermore, against a background of an estimated 360,000 patient years,
      we have found only a very small number of cases of any other form of fibrosis (1x
      retroperitoneal, 2x pleural, 2x pulmonary, 1x interstitial pulmonary changes), in
      part combined with other risk factors and confounding variables. This closely
      matches 4 reports available from WHO (1x retroperitoneal, 3x pleural fibrosis).
      In addition, only 5 other possibly related conditions (3x pleural effusion, 1x
      pleuritis, 1x pericarditis) were identified in the lisuride adverse drug reaction
      database of Schering, Berlin. CONCLUSIONS: No link has been found between
      lisuride use and fibrotic cardiac valvulopathy, in agreement with the 5-HT(2B)
      receptor antagonist effect of this drug. The very low incidence of spontaneous
      reports of any other fibrosis could be even compatible with an association by
      chance in the population exposed to lisuride. Although close monitoring for this
      kind of side effects is still to be recommended in the therapy with lisuride, our
      data do not support the concept of a class effect suggesting that all ergot
      derived drugs and especially DA receptor agonists with some chemical similarity
      to the ergot structure will cause or facilitate cardiac valvulopathies as
      observed with pergolide.

PMID- 16614542
TI  - A double-blind, placebo-controlled, crossover trial of topiramate in essential
      tremor.
AB  - The antiepileptic drug topiramate has been reported to improve essential tremor,
      but clinical trials have been small and of unsatisfactory design. We undertook a
      double-blind, placebo-controlled crossover study of topiramate in essential
      tremor, using accelerometry, spirography, and an activities of daily living
      questionnaire. Sixteen subjects were recruited between January and June 2002.
      Three withdrew consent, 13 commenced the study, and 10 finished it. Subjects were
      assessed at baseline and after 2, 4, and 6 weeks of treatment (placebo or
      topiramate doses 25, 50, and 100 mg daily). Following a washout period of 1 week,
      patients crossed over to the alternate arm of the study. Statistical analysis
      followed the method described by Altman. There was no period effect or treatment
      period interaction. No outcome measure improved significantly in the active
      treatment period as compared with the placebo control period, although 4 of the
      10 patients improved in at least 2 of the 3 outcome measures during the active
      treatment phase, and none during the control treatment phase. This study provided
      no evidence of therapeutic benefit of topiramate in essential tremor. A
      marginally larger study would be required formally to exclude a useful
      therapeutic effect. To achieve a study with a power of 80% to exclude the null
      hypothesis, at least 17 patients would be required using accelerometry, 19 using
      spirography, and 2,00 using an activities of daily living questionnaire.

PMID- 16614543
TI  - Diagnosing major depressive disorder: II: is there justification for compound
      symptom criteria?
AB  - The DSM-IV symptom inclusion criteria for the diagnosis of major depressive
      disorder (MDD) are constructed in three ways: single symptom criteria, compound
      criteria encompassing opposite variants of the same disturbance, and compound
      criteria encompassing related problems. In the present report from the Rhode
      Island Methods to Improve Diagnostic Assessment and Services project, we tested
      the following three hypotheses: (1) the components of compound-opposite criteria
      rarely occur simultaneously, (2) the components of the compound-related criteria
      frequently occur simultaneously, and (3) the components of the compound-related
      criteria more frequently co-occur than other pairs of the MDD criteria. We also
      examined how many patients would be rediagnosed if the compound criteria were
      split into separate items. One thousand eight hundred psychiatric outpatients
      were evaluated with a semistructured diagnostic interview. We inquired about all
      of the DSM-IV diagnostic criteria for MDD for all patients. As hypothesized, the
      symptoms of the compound-opposite criteria usually did not co-occur, whereas the
      symptoms of the compound-related criteria frequently were present simultaneously.
      However, the results also indicated that other pairs of symptoms were as likely
      to co-occur, and were as strongly associated with each other, as the symptoms of
      the compound-related criteria. Thus, the findings provide mixed support for the
      assumptions hypothesized to underlie the composition of the DSM-IV criteria for
      MDD. When the compound criteria were subdivided and the diagnostic threshold for
      MDD was kept constant, only a small percentage of patients was reclassified from
      a noncase to a case. The implications of these results for constructing
      diagnostic criteria, and for developing measures to assess the severity of
      depression, are discussed.

PMID- 16614544
TI  - Does the clinical course of depression determine improvement in symptoms and
      quality of life?
AB  - Clinical course factors characterizing individuals' history with depression may
      be helpful in predicting treatment-related change in quality of life (QOL). Such
      factors have been studied in relation to symptomatic change with mixed results.
      This 9-week single-blind treatment trial using reboxetine (1 week placebo lead
      in) evaluated the impact of age of onset, history of antidepressant treatment,
      duration of index episode, number of past episodes, and the presence of
      precipitating stress on depressed individuals' treatment response. We found that
      QOL did not normalize along with clinical remission in all areas. Using
      multivariate analysis, we found that age of onset, history with antidepressants,
      and the presence of identifiable precipitating stress were all significant
      predictors of QOL change (controlling for symptomatic change); some factors also
      predicted symptomatic improvement. Our results support the trend of
      distinguishing between treatment-related change in QOL and symptomatic change and
      suggest clinical course factors as promising predictors of QOL.

PMID- 16614545
TI  - Variety and intensity of emotions in nightmares and bad dreams.
AB  - Nightmares are usually defined as frightening dreams that awaken the sleeper.
      This study uses the waking criterion to distinguish between nightmares and bad
      dreams and investigated the variety and intensity of emotions reported in each
      form of disturbing dream. Ninety participants recorded their dreams for 4
      consecutive weeks and, for each dream recalled, noted the emotions present and
      their intensities on a 9-point scale. Thirty-six participants reported at least
      one nightmare and one bad dream over the 4 weeks covered by the log, while 29
      reported having had at least one bad dream but no nightmares. Nightmares were
      rated as being significantly (p < 0.001) more intense than bad dreams. Thirty
      percent of nightmares and 51% of bad dreams contained primary emotions other than
      fear. The findings support the claim that awakening can serve as an indirect
      measure of nightmare intensity and raise important implications for the
      operational definition of nightmares.

PMID- 16614546
TI  - Neurocognition as a stable endophenotype in bipolar disorder and schizophrenia.
AB  - Linkage and association studies have paid increasing attention to neurocognition
      as a putative endophenotype. However, there exists little documentation of its
      trait stability in schizophrenia or bipolar disorder. Our aim was to determine
      the longitudinal stability of neurocognitive performance in bipolar versus
      schizophrenia probands. We administered a neurocognitive battery at two time
      points, approximately 5 years apart, in 16 schizophrenia and 16 bipolar disorder
      age-matched subjects. There were no significant changes over time on variables
      including education, estimated IQ, depression, psychosis, global functioning, or
      medication status. Schizophrenia subjects showed significant deterioration in one
      measure of executive functioning but no significant changes in seven of eight
      other domains. Bipolar patients showed stability over time in attentional
      measures but greater variability in other domains. These preliminary findings
      suggest that neurocognitive domains appear longitudinally stable across broad
      domains in schizophrenia. In contrast, stable functioning may be more limited to
      attentional domains in bipolar disorder.

PMID- 16614547
TI  - The long-term changes in coping strategies in schizophrenia: temporal coping
      types.
AB  - This prospective study aimed to define the long-term changes in coping strategies
      used by schizophrenia patients and their relation to clinical and psychosocial
      factors. The Coping Inventory for Stressful Situations, psychiatric scales, and
      self-report questionnaires were administered to 148 schizophrenia patients at
      admission and 16 months thereafter. Based on trends of individual coping patterns
      to show change over time, four temporal coping types were distinguished: stable
      favorable and unfavorable, and becoming favorable and unfavorable. We found that
      coping patterns of 62.2% of patients remained stable over time, became
      unfavorable among 19.6% of patients, and became favorable among 18.2% of
      patients. Each temporal coping type is associated with a specific pattern of
      changes in clinical and psychosocial variables. The findings underscore the
      clinical relevance of temporal coping types and corroborate the appropriateness
      of focusing on aspects of coping behavior in treatment and rehabilitation of
      schizophrenia patients.

PMID- 16614548
TI  - Work-related abilities in schizophrenia and HIV infection.
AB  - Schizophrenia and human immunodeficiency virus (HIV) infection both are
      associated with high rates of neurocognitive impairment. These impairments
      predict unemployment in both disorders, independent of other disease-related
      factors that may affect employment. In this study, we investigated work-related
      abilities and previous employment patterns in 27 unemployed patients with
      schizophrenia, 27 demographically matched unemployed HIV-infected participants,
      and 27 nonmatched employed HIV seropositive (HIV+) participants. All subjects
      were administered a computerized and hands-on assessment of vocational abilities
      and a comprehensive work history interview. Compared with the employed HIV+
      group, the two unemployed groups had lower estimates of maximal lifetime job
      functioning. In terms of current vocational abilities, the employed HIV+ subjects
      generally performed best, followed by the unemployed HIV+ subjects and the
      patients with schizophrenia. Although the unemployed schizophrenia subjects had
      the most decline in vocational abilities (from estimated lifetime maximum level),
      the patterns of decline were similar in the two unemployed groups and were
      suggestive of parallel impairments in frontal-subcortical functioning.

PMID- 16614549
TI  - Symptom patterns associated with chronic PTSD in male veterans: new findings from
      the National Vietnam Veterans Readjustment Study.
AB  - A subsample of 255 male Vietnam veterans from the National Vietnam Veterans
      Readjustment Study received in-depth psychiatric diagnostic interviews. This
      paper focuses on the 88 veterans with a war-related onset of PTSD. Among these
      veterans, the avoidance cluster, especially its symptoms of numbing, was most
      strongly associated with chronic PTSD; less strongly but also significantly
      associated was the hyperarousal cluster. Further analyses show that these
      associations are not artifacts of the relationship of symptom patterns to prewar
      demographic factors (race/ethnicity, socioeconomic status, age at entry into
      Vietnam), comorbidity, treatment and compensation seeking, or probable severity
      of war-related trauma. We conclude that certain symptom profiles may predict
      enduring pathological responses to trauma and therefore provide targets for
      intervention efforts.

PMID- 16614550
TI  - Risk and protective factors mediating psychological symptoms and ideological
      commitment of adolescents facing continuous terrorism.
AB  - This study evaluated symptoms, risk, and protective factors of adolescents from
      six Israeli schools exposed to continuous terrorism. All children in the grades
      selected at each school (7, 9, and 11) were administered anonymous assessment
      materials measuring posttraumatic, grief, and dissociative symptoms, as well as
      traumatic exposure, personal resilience, and family factors. A high number of
      risk factors increased the likelihood of negative symptoms. Perceived personal
      resilience served as a protective factor against symptom development, perhaps
      enforced by ideology. Girls living on the West Bank had less severe posttrauma
      and were more willing to make personal sacrifices for their country. Proactive
      interventions aimed at enhancing a child's personal resilience and ability to
      cope with continuous stress may help protect against later symptomatology
      following traumatic events. Facing terrorism, political ideology may serve a
      double edge sword: protecting against symptom development as well as contributing
      to the toxic cycle of violence.

PMID- 16614551
TI  - Treatment compliance in different types of group psychotherapy: exploring the
      effect of age.
AB  - This study examined the effect of age on attending and completing different types
      of group therapy among psychiatric outpatients, and whether cohesion among group
      members mediates the effect of age on attendance. The sample consisted of 139
      outpatients who began short-term interpretive or supportive group psychotherapy.
      Hierarchical regression analysis and Kaplan-Meier survival analysis were used to
      test the effect of age on attending and completing therapy. Mediation analysis
      was used to examine whether cohesion mediated the effect of age. Significant
      associations between age, session attendance, and termination status were found
      for patients receiving supportive group therapy. Age was directly related to
      attending and completing therapy. Quality of the relationships among patients
      (i.e., cohesion) was found to mediate the effect of age on attendance. Depending
      of the type of group therapy offered, younger patients may be at risk for poor
      treatment adherence. Difficulty forming positive relationships with other group
      members may contribute to this risk.

PMID- 16614552
TI  - Use of leverage over patients' money to promote adherence to psychiatric
      treatment.
AB  - Persons who handle money for patients with mental disabilities often use access
      to funds as leverage to promote adherence to treatment. Drawing on data from a
      five-site study involving interviews of 1011 patients at community mental health
      centers, this paper explores who provides money assistance, the predictors of
      leverage use, and its impact on patients. A substantial minority of patients
      reported having experienced leverage. Substance abuse and frequent
      hospitalization were the strongest clinical predictors, suggesting that
      functional impairment is a key determinant. Patients experiencing money leverage
      were also likely to experience other forms of leverage, and although they were
      more likely to feel coerced, they were also more likely to believe that money
      leverage was effective. Family members seemed to provoke fewer negative feelings
      as money managers. The frequency with which money leverage is used suggests
      attention is needed to both the fairness of leverage and the means of minimizing
      negative effects.

PMID- 16614553
TI  - Attributional style in the eating disorders.
AB  - Previous research has shown that patients with eating disorders have a
      characteristic cognitive bias, making internal attributions when evaluating
      negative events. However, there is less clarity about their attributions for
      positive events. There are suggestions that this cognitive style might be
      influenced by depressed mood. This study examines attributional style in the
      eating disorders for positive and negative events, independent of covariant
      effects of depression. Twenty-five eating-disordered women and 26 nonclinical
      women each completed measures of attributional style, depressed mood, and eating
      pathology. They also completed a measure of verbal intelligence (to ensure
      comparability of groups). Women with an eating disorder had a greater tendency to
      attribute negative situations to the self when compared with nonclinical women,
      even when differences in depressed mood were controlled for. There were no
      comparable differences in positive attributional biases. Women with an eating
      disorder adopt a self-blaming style when evaluating negative events, and such
      self-blame is likely to contribute to the maintenance of an eating disorder. This
      suggests that therapy for the eating disorders should include an element that
      focuses on highlighting and re-evaluating such interpretations.

PMID- 16614556
TI  - Binghamton by way of Elmira.

PMID- 16614557
TI  - The multistate learning collaborative, states as laboratories: informing the
      national public health accreditation dialogue.
AB  - The Multistate Learning Collaborative on Performance and Capacity Assessment or
      Accreditation of Public Health Departments (MLC) is an initiative undertaken with
      the Exploring Accreditation Project (EAP). The EAP is jointly funded by the
      Robert Wood Johnson Foundation (RWJF) and the Centers for Disease Control and
      Prevention (CDC), and staffed collaboratively by the Association of State and
      Territorial Health Officials (ASTHO) and the National Association of County and
      City Health Officials (NACCHO) to explore the implications and feasibility of a
      national public health accreditation system. The MLC, also financially supported
      through grants from RWJF, is designed under the auspices of the National Network
      of Public Health Institutes (NNPHI) and the Public Health Leadership Society
      (PHLS) to enhance the accreditation/assessment activities already underway in
      each of the grantee states; to promote learning among the states participating in
      the collaborative; to disseminate information to state and local health
      departments nationally; and to inform the work of the EAP. Five states with
      mature accreditation or assessment programs were selected from among 18
      applicants. This article describes the ongoing work, including breakthroughs and
      challenges, in these natural "laboratories" so that this information may be a
      resource for other states as well as nationally.

PMID- 16614558
TI  - Roles of local public health agencies within the state public health system.
AB  - OBJECTIVES: In this study we assessed the structure and function of local and
      district health agencies throughout the United States. We compared these findings
      with those from a previous national assessment done a decade earlier. METHODS: We
      surveyed the state health officers of all 50 states in the summer of 2001 in
      regard to the structures and functions of their state's local and district health
      agencies. RESULTS: Forty-seven states completed the survey for a 94 percent
      response rate. Forty-three percent have a regional or district structure in
      place. According to more than 80 percent of the respondents, local health
      departments serve all areas of their state. Local boards of health provide
      guidance and oversight in two thirds of the states. Most local health departments
      continue to perform a variety of traditional public health functions, as well as
      a variety of newly emerging responsibilities. Many local functions varied by
      geographic regions, population size, and organizational type. CONCLUSIONS: The
      study identified structural and functional changes in the local and district
      health agencies of state public health systems over the last decade. The stage is
      set for future work on the relationship between public health structure and
      function, and performance in the 21st century.

PMID- 16614559
TI  - SARS outbreak in Germany 2003: workload of local health departments and their
      compliance in quarantine measures--implications for outbreak modeling and surge
      capacity?
AB  - OBJECTIVE: Public health management of severe acute respiratory syndrome epidemic
      must be evaluated to improve contingency planning for epidemics. METHODS:
      Standardized questionnaires on case management were sent to local health
      departments of 15 of 16 states in Germany. RESULTS: Of the 384 local health
      departments who received the questionnaire, 280 (72%) completed them. They
      reported 271 suspect or probable severe acute respiratory syndrome cases under
      investigation (average 4.7). The average duration of quarantine was 5.4 days.
      Contacts without professional activity were 2.78 times more likely to stay under
      10-day quarantine than those with professional activity (CI: 0.80-9.86). Local
      health departments with at least one case under investigation had invested an
      average of 104.5 working hours. CONCLUSIONS: Our contact-case ratios may serve
      for planning for modeling in epidemics. We found discrepancies between local and
      national surveillance figures; home quarantine was frequently not applied as
      recommended and the burden on urban health departments was disproportionally
      higher. Flexibility of the national surveillance system and surge capacity for
      the prevention of future epidemics need improvement, particularly in urban health
      departments.

PMID- 16614560
TI  - Health department costs of managing persons with suspected and noncounted
      tuberculosis in New York City, Three Texas counties, and Massachusetts.
AB  - OBJECTIVES: To describe persons with suspected (did not meet the national
      tuberculosis [TB] surveillance case definition) and noncounted TB (met the TB
      case definition but transferred and were counted by another jurisdiction) and
      estimate costs incurred by public health departments for managing them. METHODS:
      We reviewed TB registry, medical records, budgets, bills, salaries,
      organizational charts, and travel/activity logs from the year 2000 at health
      departments in New York City (NYC), three Texas (TX) counties (El Paso, Hidalgo,
      and Webb), and Massachusetts (MA). We also interviewed or observed personnel to
      estimate the time spent on activities for these patients. RESULTS: In 2000, NYC
      and MA had more persons with suspected (n = 2,996) and noncounted (n = 163) TB
      than with counted (n = 1,595) TB. TX counties had more persons with counted TB (n
      = 179) than with suspected (n = 55) and noncounted (n = 15) TB. Demographic and
      clinical characteristics varied widely. For persons with suspected TB, NYC spent
      an estimated $1.7 million, with an average cost of $636 for each person; TX
      counties spent $60,928 ($1,108 per patient); and MA spent $1.1 million ($3,330
      per patient). For persons with noncounted TB, NYC spent $303,148 ($2,180 per
      patient), TX counties spent $40,002 ($2,667 per patient), and MA spent $84,603
      ($3,525 per patient). CONCLUSIONS: Health departments incurred substantial costs
      in managing persons with suspected and noncounted TB. These costs should be
      considered when allocating TB program resources.

PMID- 16614561
TI  - Tuberculosis cases in Wisconsin: documentation of treatment improvement and
      completion of treatment, 2000-2002.
AB  - OBJECTIVE: In 2000, the Wisconsin Strategic Plan for the Elimination of
      Tuberculosis (TB) sets goals of 90 percent treatment completion and 95 percent
      documentation of treatment improvement for all reported cases of TB. This study
      measures the success in achieving these goals. METHODS: Data were abstracted from
      charts of all 249 reported TB cases during 2000-2002. Treatment completion was
      considered for patients indicated for completion in 12 months or less.
      Documentation of treatment improvement included therapy adherence, sputum culture
      conversion, and chest radiograph improvement for pulmonary cases, and therapy
      adherence and clinical improvement for extrapulmonary cases. RESULTS: Treatment
      completion was measured in 204 of 249 TB cases; 87.1 percent completed treatment
      in 12 months or less. There was a significant difference in completion by site of
      disease, 89.9 percent for pulmonary cases and 66.1 percent for extrapulmonary
      cases (P < .01). Documentation of treatment improvement was 61.2 percent among
      pulmonary cases and 83.6 percent among extrapulmonary cases (P < .01). During the
      study period, there was a significant decrease in documentation rates for
      patients with pulmonary TB (P < .01). CONCLUSIONS: The goal of 90 percent
      treatment completion was nearly accomplished but the goal of 95 percent
      documentation of treatment improvement was not achieved. Barriers to TB treatment
      in Wisconsin need to be identified. Case management of TB is necessary for
      control and prevention of TB.

PMID- 16614562
TI  - Diffusion of local restaurant smoking regulations in Massachusetts: identifying
      disparities in health protection for population subgroups.
AB  - OBJECTIVES: The objectives of this study were to examine the diffusion of smoke
      free restaurant regulations and identify socioeconomic and racial/ethnic
      disparities in health protection from secondhand smoke exposure in restaurants.
      METHODS: We examined the relationship between adoption of local smoking
      regulations by restaurants for each of the 351 cities and towns in Massachusetts
      and a number of individual variables over nine time points, starting when there
      were no 100% smoke-free restaurant regulations and ending with the eventual
      imposition of the statewide ban on smoking in restaurants and bars. RESULTS: We
      found that over the 10 years before the statewide ban went into effect, only 36
      percent of the total population was covered by local regulations that protected
      them from secondhand smoke exposure in restaurants. We also observed a
      substantial disparity in protection based on educational status, with up to 7
      percentage points fewer nongraduates protected by local smoke-free restaurant
      regulations.

PMID- 16614563
TI  - How reliably do community members audit the neighborhood environment for its
      support of physical activity? Implications for participatory research.
AB  - Environmental audits are used to assess supports for physical activity in the
      community. Understanding the suitability of such instruments for use by community
      members is crucial for advocacy and participatory research. This study examined
      the reliability of an audit instrument filled out by trained researchers and
      untrained community members. Two researchers and five community members conducted
      environmental audits on a total of 335 street segments in lower-income areas in
      St Louis, Missouri (representing a "low-walkable city"), and Savannah, Georgia
      (representing a "high-walkable" city). The audit tool consisted of six major
      sections--land use environment, recreational facilities, transportation
      environment, aesthetics, signage, and social environment. Interrater agreement
      between researchers and community members was assessed using percent observed
      agreement and the kappa statistic. According to observed agreement, the majority
      of audit items (67 of 76) had substantial to almost perfect agreement (> or
      =0.60) between researchers and community members. However, much lower agreement
      was observed using the kappa statistic (only 8 of 76 items with kappas > or
      =0.60). With some formal training, this audit tool may be useful for advocacy and
      participatory research to assess the activity friendliness of neighborhood
      environments.

PMID- 16614564
TI  - Identifying Health Maintenance Organization membership through self-report of
      health plan name: ascertainment and reliability.
AB  - OBJECTIVE: To evaluate the feasibility and reliability of (1) identifying Health
      Maintenance Organization (HMO) membership by ascertaining self-reported health
      plan name in a telephone survey and (2) using external information to determine
      whether the plan was an HMO. METHODS: Respondents to the 1999-2001 Massachusetts
      Behavioral Risk Factor Surveillance System (BRFSS) and the 1999 Massachusetts
      Colorectal Cancer (CRC) survey were asked to name their health plan. The authors
      used information from external sources to classify the plan as an HMO or a non
      HMO. Test-retest reliability of reported plan name was examined overall, by
      demographic characteristics, and by health plan name. Reliability of HMO
      classification was tested with the kappa statistic. RESULTS: More than 88 percent
      of respondents with commercial health insurance provided their health plan name;
      84 percent reported a plan that could be assigned as either an HMO or a non-HMO.
      The percentage whose HMO status could be assigned differed by demographic
      characteristics. Among those assigned, the distribution of specific HMOs among
      survey respondents was similar to the distribution reported by the Massachusetts
      Division of Insurance. In a subsample, 78 percent reported the same health plan
      during a follow-up interview. Agreement was higher for men, and differed
      according to the plan reported at the first time point. Kappa for HMO
      classification from health plan name was 0.87. CONCLUSIONS: Self-report of health
      plan name is a feasible and reliable method to ascertain health insurance
      information in a telephone interview.

PMID- 16614565
TI  - UNC certificate program in core public health concepts: lessons learned.
AB  - OBJECTIVES: Public health workers need to be trained in the core public health
      sciences. The University of North Carolina at Chapel Hill School of Public Health
      created a Certificate in Core Public Health Concepts to meet the training needs
      of public health workers, primarily those working in state or local public health
      agencies. METHODS: This article examines the demographic, educational, job
      classification, and workplace characteristics of certificate program applicants
      from the first 3 years of the program. In addition, this article assesses student
      performance and graduate satisfaction with the program. RESULTS: Among the 273
      applications reviewed, the majority were from females. They worked in a variety
      of job classifications: 19% were public health agency workers, 64% were public
      health system workers, and 17% worked in other occupations. Nearly all students
      received High Pass or Pass grades on courses. Initial data on graduate
      satisfaction with the program are positive. CONCLUSIONS: Implications of the
      findings for training the public health workforce are discussed.

PMID- 16614566
TI  - Measuring health disparities.

PMID- 16614568
TI  - Managing in the information age: preventing "electronic fatigue syndrome".

PMID- 16614569
TI  - National committee explores accreditation for state and local health departments.

PMID- 16614570
TI  - Short-term adaptation to vertical yoked prisms.
AB  - PURPOSE: The purpose of this study was to investigate short-term adaptation to
      vertical yoked prisms in visually normal subjects as well as to develop normative
      data for future comparative purposes in patients with acquired brain injury.
      METHODS: A full-body enclosure containing a calibrated laser pointer was used to
      assess egocentric localization (i.e., one's perceived sense of "straight ahead")
      in total darkness. Fourteen visually normal subjects were tested in a
      counterbalanced manner under both experimental (20 pd base-down) and control
      (plano or zero power) test conditions with each test condition lasting 1 hour. A
      rating scale questionnaire was also administered to assess quantitatively
      subjective adaptation to the yoked prisms. RESULTS: Group mean egocentric
      localization showed approximately 50% adaptation during the 1-hour test period.
      Subjective adaptation results were similar. CONCLUSION: The findings suggest that
      rapid perceptually driven, sensorimotor adaptation occurred as assessed both
      objectively and subjectively in response to vertical yoked prisms. These results
      are similar to those found in other experiments involving short-term adaptation
      to optical rearrangements.

PMID- 16614571
TI  - Sequential tilt and tilted power of thin lenses.
AB  - PURPOSE: The purposes of this article were, for any sequence of tilts applied to
      a thin lens, to calculate an equivalent turn and single tilt, to show how to use
      the equivalent turn and tilt to calculate the tilted power of the lens, and,
      given the desired tilted power, to calculate the power of the untilted lens
      necessary to compensate for the effects of tilt. The untilted lens may be
      stigmatic (spherical) or astigmatic (spherocylindrical). METHODS: The analysis
      makes use of rotation matrices to represent rotation in space and previous work
      in third-order optics on oblique central refraction. RESULTS: Equations are
      presented for calculating the combination of turn and tilt that is equivalent to
      any sequence of tilts. They are specialized for the particular case of
      combinations of faceform and pantoscopic tilts and allow the decomposition of an
      arbitrary tilt into a combination of turn and pantoscopic and faceform tilts. The
      equations also lead to a procedure for calculating or compensating for the tilted
      power of a sequentially tilted thin lens. CONCLUSIONS: Previous work on the
      effect of tilt on thin lenses has been generalized to handle combinations of
      arbitrary tilts.

PMID- 16614575
TI  - Prevalence of high astigmatism, eyeglass wear, and poor visual acuity among
      Native American grade school children.
AB  - PURPOSE: The purpose of this study was to examine the prevalence of astigmatism
      and poor visual acuity and rate of eyeglass wear in grade school children who are
      members of a Native American tribe reported to have a high prevalence of large
      amounts of astigmatism. METHODS: Vision screening was conducted on 1,327 first
      through eighth grade children attending school on the Tohono O'odham Reservation.
      Noncycloplegic autorefraction was conducted on the right and left eye of each
      child using the Nikon Retinomax K+ autorefractor, and monocular recognition
      acuity was tested using ETDRS logarithm of the minimum angle of resolution
      (logMAR) letter charts. RESULTS: Tohono O'odham children had a high prevalence of
      high astigmatism (42% had > or = 1.00 D in the right or left eye) and the axis of
      astigmatism was uniformly with-the-rule. However, only a small percentage of
      children arrived at the vision screening wearing glasses, and the prevalence of
      poor visual acuity (20/40 or worse in either eye) was high (35%). There was a
      significant relation between amount of astigmatism and uncorrected visual acuity
      with each additional diopter of astigmatism resulting in an additional 1 logMAR
      line reduction in visual acuity. CONCLUSIONS: Uncorrected astigmatism and poor
      visual acuity are prevalent among Tohono O'odham children. The results highlight
      the importance of improving glasses-wearing compliance, determining barriers to
      receiving eye care, and initiating public education programs regarding the
      importance of early identification and correction of astigmatism in Tohono
      O'odham children.

PMID- 16614576
TI  - Refraction and aberration across the horizontal central 10 degrees of the visual
      field.
AB  - PURPOSE: The purpose of this study was to measure refraction and aberrations
      across the horizontal central visual field. METHODS: Cycloplegic refraction was
      measured on eight subjects at 13 points across the horizontal central 10 degrees
      of the retina using a Hartmann-Shack wavefront sensor. Refractions were converted
      into mean sphere (M), 90 degrees to 180 degrees astigmatism (J180), and 45
      degrees to 135 degrees astigmatism (J45) components. For five subjects, higher
      order aberrations were determined at the center and edges of the field. RESULTS:
      Subtle changes in refraction were found to exist across the central 10 degrees of
      the retina, with changes in mean best sphere varying by up to half a diopter
      across this region and with smaller changes in astigmatism. Horizontal coma, but
      no other higher-order aberrations, varied systemically across the visual field;
      it varied linearly with angle but at different rates for the different subjects.
      CONCLUSION: Subtle changes in cycloplegic refraction exist across the horizontal
      central 10 degrees of the retina. The results indicate the need for correct
      alignment when measuring objective refraction.

PMID- 16614577
TI  - The impact of artificial light scatter on scanning laser tomography.
AB  - PURPOSE: The impact of cataract (which frequently occurs alongside glaucoma) on
      scanning laser tomography (SLT) is poorly understood. The aim of this pilot study
      was to determine the impact of artificial light scatter on SLT estimates of optic
      nerve head (ONH) topography. METHODS: The sample comprised 10 healthy, young
      subjects of mean age 23.5 years. One eye of each subject was randomly selected.
      Cells filled with increasing concentrations of 0.50-microm diameter polystyrene
      microspheres were prepared. The cells were mounted in front of the objective lens
      of the Heidelberg Retina Tomograph (HRT) II and were tilted at an angle of 20
      degrees to eradicate any surface reflections. Three sets of ONH scans were
      initially acquired without any light scatter cell in place and then three further
      sets were acquired for each of four different concentrations of microspheres in a
      randomized order. The impact of artificial light scatter on cup-to-disc area
      ratio, cup volume, rim volume, cup shape measure, height variation contour, and
      mean retinal nerve fiber layer (RNFL) thickness was evaluated. RESULTS: Repeated
      measures analysis of variance showed that there was no significant change in cup
      to-disc area ratio, cup volume, rim volume, height variation contour, cup shape
      measure, or mean RNFL thickness as a function of increasing light scatter cell
      concentration. CONCLUSION: Artificial light scatter had no statistically
      significant impact on the stereometric parameters of the HRT II. From a clinical
      perspective, useful SLT data can be acquired with confidence from patients with
      diagnosed/suspected glaucoma and concomitant cataract.

PMID- 16614578
TI  - Accuracy of the contrast sensitivity card test for infants: retest variability
      and prediction of spatial resolution.
AB  - PURPOSE: We assessed the retest variability of a new contrast sensitivity (CS)
      card procedure and its ability to predict spatial resolution. METHODS: Twenty
      four 3-month-olds were tested twice with the CS cards and once with the Teller
      acuity cards (TAC) within a single session. RESULTS: Coefficient of repeatability
      (COR) analysis revealed that retest variability of the new cards is superior to
      that of an earlier prototype at low to mid spatial frequencies. Furthermore,
      retest variability is comparable to that of infant visual evoked potential
      studies and the Vistech 6500, a chart commonly used to measure CS in adults.
      Finally, estimates of visual acuity based on the CS cards were consistent with
      those provided by the TAC (although CS-based estimates were generally lower
      overall). CONCLUSIONS: Given its reliability and accuracy, the new CS card
      procedure has good potential as a clinical tool for assessing spatial vision in
      infants and toddlers.

PMID- 16614579
TI  - Advantages of toric scleral lenses.
AB  - PURPOSE: The purpose of this study was to investigate whether back surface toric
      scleral lenses stabilized (i.e., returned to their original position after
      rotation) and how long the return times were. Return time was studied in relation
      with actual wearing time and comfort; moreover, the performance of the spherical
      scleral lens was compared with the toric scleral lens design. METHODS: Toric
      scleral lenses were rotated clockwise and counterclockwise over 60 degrees.
      Return times and the actual wearing time were recorded. Results were transformed
      into nasal and temporal return times for symmetry reasons. The present and former
      types of correction were compared for comfort (ranging from 0: very poor to 10:
      excellent) and regular wearing time. All the subjects attended regular follow-up
      visits. RESULTS: Forty-three subjects (43 lenses) entered the study. All the
      lenses returned to the original position within a median of 4 seconds after nasal
      rotation and 6 seconds after temporal rotation. A significant correlation was
      found between mean return times and actual wearing time (r = 0.63). Significant
      increases in median comfort (from 6-8) and median wearing time (from 15-16 hours)
      were demonstrated when the toric scleral lens designs were compared with the
      former type of correction (both p < 0.001). Median comfort and median wearing
      time also increased significantly after changing from spherical scleral lenses to
      the toric design (from 7-8 and from 14-16 hours, both p < 0.001, n = 27 eyes).
      CONCLUSIONS: Toric scleral lenses returned rapidly to their original position
      after rotation. The flattest meridian of the toric scleral lenses stabilized
      symmetrically. Patient interviews demonstrated differences in comfort and wearing
      time in favor of the toric design.

PMID- 16614580
TI  - Comparison of subjective heterophoria testing with a phoropter and trial frame.
AB  - PURPOSE: Subjective measurement of the oculomotor deviation at both distance and
      near is a standard test in optometric practice. A number of procedures are
      available to the practitioner, and previous studies have demonstrated differences
      in the repeatability of many of the techniques. However, it is unclear whether
      testing the subject through a phoropter or in free space (trial frame) will alter
      the oculomotor deviation. METHODS: Distance and near heterophoria was measured in
      60 visually normal subjects between 20 and 34 years of age using the Von Graefe
      (VG), Maddox Rod (MR), and Modified Thorington (MT) procedures. The deviation was
      assessed for viewing distances of 6 m and 0.40 m using both a phoropter and trial
      frame. To examine the repeatability of each technique, the deviation was measured
      on two separate occasions for each procedure, with the two sessions being
      separated by at least 24 hours. RESULTS: The mean vertical deviations at both
      distance and near were extremely close to orthophoria, and only minimal variation
      was observed. However, the MR procedure, when used with a trial frame, gave the
      best repeatability for measuring vertical deviations both at distance and near.
      Regarding horizontal deviations, the repeatability was better for all three
      procedures when using a trial frame compared with the phoropter. The best
      repeatability at distance and near was observed when the MT and MR techniques,
      respectively, were used with the trial frame. Consistent with previous reports,
      the VG procedure had poor repeatability, especially when used with the phoropter,
      and the mean findings showed a greater exo deviation when compared with the other
      two techniques. CONCLUSIONS: Testing oculomotor deviations in free space provides
      a more repeatable response than when using a phoropter. Accordingly, we recommend
      that subjective measurements of heterophoria in the clinical setting can best be
      quantified using either the MR or MT techniques in free space.

PMID- 16614581
TI  - Assessment of the validity of in vivo methods of measuring human macular pigment
      optical density.

PMID- 16614583
TI  - Comparing intravenous amiodarone or lidocaine, or both, outcomes for inpatients
      with pulseless ventricular arrhythmias.
AB  - OBJECTIVE: To compare survival rates of patients with in-hospital cardiac arrest
      due to pulseless ventricular tachycardia/ventricular fibrillation treated with
      lidocaine, amiodarone, or amiodarone plus lidocaine. DESIGN: Multicenter
      retrospective medical record review. SETTING: Three academic medical centers in
      the United States. PATIENTS: Hospitalized adult patients who received amiodarone,
      lidocaine, or a combination for pulseless ventricular tachycardia/ventricular
      fibrillation between August 1, 2000, and July 31, 2002. MEASUREMENTS AND MAIN
      RESULTS: Data were collected according to the Utstein style. In-hospital
      proportion of patients living at 24 hrs and discharge were analyzed using chi
      square analysis. Of the 605 patient medical records reviewed, 194 met criteria
      for inclusion (n=79 for lidocaine, n=74 for amiodarone, n=41 for combination).
      Available data showed no difference in proportion of patients alive 24 hrs post
      cardiac arrest (p=.39). Cox regression analysis indicated a decreased likelihood
      of survival in patients with pulseless ventricular tachycardia/ventricular
      fibrillation as an initial rhythm as compared with those who presented with
      bradycardia followed by pulseless ventricular tachycardia/ventricular
      fibrillation and in those patients who received amiodarone as compared with
      lidocaine. However, only 14 patients (25%) in the amiodarone group received the
      recommended initial 300-mg intravenous bolus, and amiodarone was administered an
      average of 8 mins later in the code compared with lidocaine (p<.001).
      CONCLUSIONS: These results generate the hypothesis that inpatients with cardiac
      arrest may have different benefits from lidocaine and amiodarone than previously
      demonstrated. Inadequate dosing and later administration of amiodarone in the
      code were two confounding factors in this study. Prospective studies evaluating
      these agents are warranted.

PMID- 16614584
TI  - Does fast-track treatment lead to a decrease of intensive care unit and hospital
      length of stay in coronary artery bypass patients? A meta-regression of
      randomized clinical trials.
AB  - OBJECTIVE: Evaluation of randomized, controlled clinical trials studying fast
      track treatment in low-risk coronary artery bypass grafting patients. DESIGN:
      Meta-regression. PATIENTS: Low-risk coronary artery bypass grafting patients.
      INTERVENTIONS: Fast-track treatments including (high or low) anesthetic dose,
      normothermia vs. hypothermia, and extubation protocol (within or after 8 hrs).
      MEASUREMENTS: Number of hours of intensive care unit stay, number of days of
      hospital stay, prevalence of myocardial infarction, and death. Furthermore,
      quality of life and cost evaluations were evaluated. The epidemiologic and
      economic qualities of the different trials were also assessed. MAIN RESULTS: A
      total of 27 studies evaluating fast-track treatment were identified, of which 12
      studies were with major and 15 were without major differences in extubation
      protocol or anesthetic treatment or both. The use of an early extubation protocol
      (p=.000) but not the use of a low anesthetic dose (p=.394) or normothermic
      temperature management (p=.552) resulted in a decrease of the total intensive
      care unit stay of low-risk coronary artery bypass grafting patients. Early
      extubation was found to be an important determinant of the total hospital stay
      for these patients. An influence of the type of fast-track treatment on mortality
      or the prevalence of postoperative myocardial infarction was not observed. In
      general, the epidemiologic and economic qualities of included studies were
      moderate. CONCLUSIONS: Although fast-track anesthetics and normothermic
      temperature management facilitate early extubation, the introduction of an early
      extubation protocol seems essential to decrease intensive care unit and hospital
      stay in low-risk coronary artery bypass grafting patients.

PMID- 16614585
TI  - A pilot study of vaginal flora changes with randomization to cessation of
      douching.
AB  - OBJECTIVES: The objectives of this study were to determine whether women who
      douche regularly would enter a randomized trial of douching cessation or
      continuation, whether they would adhere to the assigned behavior, and whether
      there was a dramatic impact on vaginal flora. GOAL: The goal of this study was to
      determine the feasibility of a large, definitive trial of douching cessation.
      STUDY DESIGN: Women who douched at least weekly and who had either bacterial
      vaginosis or normal flora by Gram stain were assigned at random either to
      continue douching or to stop for 8 weeks. Vaginal Gram stains were obtained every
      7 days from each woman. RESULTS: Forty-eight women were randomized. Those
      assigned to continue reported douching during 77% of study weeks; those assigned
      to stop denied douching in 94% of weeks. No dramatic differences in flora were
      observed between women in the continue versus stop groups. CONCLUSION: A large
      randomized trial of douching cessation is feasible.

PMID- 16614586
TI  - Decline in the prevalence of antibodies to herpes simplex virus types 1 and 2
      among Israeli young adults between 1984 and 2002.
AB  - OBJECTIVE: The objective of this study was to estimate the seroprevalence of
      herpes simplex virus (HSV) types 1 and 2 in male and female soldiers discharged
      from the Israel Defense Force (IDF) over a period of 18 years. GOAL: The goal of
      this study was to study the secular trends of HSV-1 and HSV-2 infection rates in
      Israeli young adults. STUDY DESIGN: Three consecutive cross-sectional studies
      were carried out on stored sera of systematic random samples of soldiers (median
      age = 20.8) discharged from the IDF in 1984-1985, 1992-1993, and 2001-2002. HSV-1
      and -2 seroprevalence was analyzed using indirect IgG enzyme-linked immunosorbent
      assay for type-specific antibodies. RESULTS: There was a significant decrease in
      HSV-1 and HSV-2 seropositivity rates at discharge from the army and an estimated
      10-fold decline in the incidence rates of HSV-2 infection during the military
      service over the last 2 decades. CONCLUSIONS: The decline in HSV-1 seroprevalence
      rate is similar to that reported from other industrialized countries. The
      decrease in HSV-2 seroprevalence and transmission rates among Israeli young
      adults is steeper than that reported from Western countries.

PMID- 16614587
TI  - School-based screening for Chlamydia trachomatis and Neisseria gonorrhoeae among
      Philadelphia public high school students.
AB  - CONTEXT: The prevalence of sexually transmitted diseases among adolescents is
      high. Innovative screening and treatment programs need evaluation. OBJECTIVES:
      The objectives of this study were to identify, treat, and describe the prevalence
      of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infections among
      Philadelphia public high school students. DESIGN: We analyzed cross-sectional
      data from the first year of an annual program offering education, screening, and
      treatment for CT and GC. For the school year analyzed, screening took place
      between January 2003 and June 2003. RESULTS: In the first year, 19,394 students
      aged 12-20 years were voluntarily tested; 1,052 students were identified with GC,
      CT, or both; 1,051 received treatment. Prevalence of CT among females (95%
      confidence interval [CI] = 8.1) was 3.3 times higher than among males (95% CI =
      2.5%). Attending disciplinary schools and residing in high reported morbidity
      areas were also related to higher prevalence of CT and GC. CONCLUSIONS: A high
      prevalence of CT infections was identified among Philadelphia public high school
      students. This program demonstrated the effectiveness of a school-based screening
      program to identify and treat these infections.

PMID- 16614588
TI  - Nested case-control study of cervical mucosal lesions, ectopy, and incident HIV
      infection among women in Cape Town, South Africa.
AB  - OBJECTIVE: The objective of this study was to test whether cervical mucosal
      lesions and ectopy increase women's susceptibility to HIV infection. STUDY
      DESIGN: HIV-seronegative women ages 35 to 65 years (n = 5773) enrolled into a
      cervical cancer screening trial were followed for up to 36 months. All HIV
      seroconverters (n = 86) in the cohort were compared with randomly selected
      controls (n = 324) who did not seroconvert. Magnified photographs of the cervix
      taken during speculum examination at enrollment were evaluated for cervical
      mucosal lesions and ectopy using standard criteria. RESULTS: The presence of
      mucosal lesions (observed among 19% of controls) was associated with increased
      risk of HIV seroconversion (adjusted odds ratio [AOR] = 1.93; 95% confidence
      interval [CI] = 1.07-3.48). Ectopy extending over >20% of the cervix was also
      associated with HIV seroconversion (AOR = 2.18; 95% CI = 1.01-4.69). CONCLUSIONS:
      Visible lesions of cervical mucosa and cervical ectopy may be markers of
      increased susceptibility to HIV infection among women. Protection of the mucosa
      of the cervix may provide an important approach for new HIV prevention
      technologies.

PMID- 16614589
TI  - Exploring HIV prevention needs for nongay-identified black and African American
      men who have sex with men: a qualitative exploration.
AB  - OBJECTIVES: The objectives of this study were to describe ways in which black men
      who have sex with men (MSM) identify their sexual identities, explore their views
      of HIV prevention interventions, and assess barriers to recruiting men for future
      study participation. STUDY DESIGN: Focus groups were conducted with 25 black MSM
      who have sex with women. Thematic analyses were conducted. RESULTS: Factors
      influencing HIV/AIDS prevention perceptions included men's responses and
      reactions to homosexual labels and vies, sexual behaviors, contextual factors,
      and self-worth. Men also expressed a need to discuss ambivalent feelings about
      same-sex sexual encounters. CONCLUSION: The qualitative study provided insights
      into the significance of sexual identity and sexual labeling for black MSMs' HIV
      prevention needs.

PMID- 16614590
TI  - Association of Chlamydia trachomatis Serovar Ia infection with black race in a
      sexually transmitted diseases clinic patient population in Birmingham, Alabama.
AB  - BACKGROUND: Black race is a risk marker for Chlamydia trachomatis infection.
      Because chlamydial serovar and race could both influence the transmission
      dynamics of chlamydia, studies characterizing serovars in a predominantly black
      population are of interest, yet remain sparse. STUDY DESIGN AND GOALS: C.
      trachomatis isolates collected consecutively from 109 female and 98 male patients
      presenting to a sexually transmitted disease clinic in Birmingham, Alabama, were
      serotyped. Our goal was to evaluate serovar distribution and associated
      demographic characteristics in a predominantly black population. RESULTS: The
      median age was 23 years and 91% were black. Serovars E (29%), D (19%), F (19%),
      Ia (16%), and J (9%) were the most prevalent. Blacks were less often infected
      with serovar E (30% vs. 41%) and J (9% vs. 24%), but more often infected with
      serovar Ia (17% vs. 0%) compared with individuals of other racial groups (P =
      0.07). The overall serovar distribution did not significantly differ by gender or
      age; however, serovar Ia infections were associated with older age (21% in age
      >or=23 years vs. 10% in those age <23 years; P = 0.03). CONCLUSIONS: Although the
      overall C. trachomatis serovar distribution in this predominantly black
      population in Birmingham was similar to that reported elsewhere, serovar Ia was
      only found in blacks, in whom it was commonly isolated. Finding differences in
      serovar distribution by race, particularly serovar Ia, may be of epidemiologic
      significance and deserves verification in similar cohorts.

PMID- 16614591
TI  - [Malaria: a medical and economic problem].

PMID- 16614593
TI  - [Clinical relevance of benzodiazepines].

PMID- 16614592
TI  - [Management and prevention of nutritional risk. What do we expect from hospitals
      and nursing homes?].

PMID- 16614594
TI  - [The new French hospital financing system: challenges for 2006].

PMID- 16614595
TI  - [The new French hospital financing system and public hospitals: will there be a
      moment of truth?].

PMID- 16614596
TI  - [Retrospective analysis of 107 imported adult cases of malaria. Experience report
      of uncomplicated falciparum malaria treatment in adults with oral atovaquone
      proguanil].
AB  - OBJECTIVES: The principal aim of this study was to assess the efficacy of the
      combination of oral atovaquone and proguanil (AP) in routine treatment of
      uncomplicated falciparum malaria in recent visitors to the tropics. We also
      analyzed the epidemiologic, clinical and hematologic characteristics of these
      patients with imported malaria. METHODS: This retrospective study reviewed the
      records of 107 cases of imported malaria, treated in the Tropical Disease Unit of
      Bordeaux University Hospital (France). RESULTS: More than 75% had uncomplicated
      falciparum malaria; 10 developed complications, and one died. Average time from
      fever onset to first medical consultation was 4.8 days. Less than 10% had used
      physical measures of prevention against mosquito bites, and nearly 65% had not
      used chemoprophylaxis. The most frequent hematologic abnormalities were
      eosinopenia (84%) and thrombocytopenia (75%). In more than 30% of cases, another
      disease was also present. The oral AP combination was administered to more than
      86% of patients with uncomplicated falciparum malaria (n=72). Tolerance was
      excellent and only one treatment failure was observed, associated with digestive
      disorders. CONCLUSION: Better information for travelers and general practitioners
      is required to reduce the number of cases of imported malaria and to shorten the
      delay between symptom onset and specific treatment. The oral AP combination
      appears to be a safe and effective treatment for uncomplicated imported
      falciparum malaria.

PMID- 16614597
TI  - [Prevention and treatment of undernutrition in hospitals and institutions. Cross
      sectional study in 116 health facilities in Haute-Normandie (France), 2003].
AB  - INTRODUCTION: The elderly, especially the institutionalized elderly, are at risk
      of undernutrition, which institutions do not appear to identify or treat
      adequately. OBJECTIVE: To identify activities undertaken to manage and prevent
      undernutrition in the elderly in institutions in Haute-Normandy (France).
      METHODS: In February 2003, all institutions in Haute-Normandy likely to house the
      elderly received questionnaires for this cross-sectional study: public hospitals
      (PH) responded, private hospitals (PRH), and retirement homes, classified into
      two groups according to the medical services provided (RH, retirement homes, NH,
      nursing homes). RESULTS: Slightly more than half the institutions responded:
      34/36 PH, 20/28 PRH, and 62/161 RH and NH. Half Only 22% reported specific
      protocols for undernutrition; this figure ranged from 30.3% for PH to 13.6% for
      RH (p=0.22). Patients' food intake was tracked at 67% of the institutions - from
      81.8% of the PH to 45.5% of the retirement homes (p=0.10). Meal choices were
      offered at 54% of the institutions: 85.0% of PRH hospitals offered a choice, but
      only 45.4% of the PH and of the RH (p=0.01). Overall, 51% asked about eating
      habits and preferences at admission. Nurses' aides provided help during meals in
      46.9% of institutions, and 49% considered they had sufficient staff to help
      patients during meals: 95.5% in RH, but only 20.7% in PH (p<0.001). DISCUSSION:
      Institutions for the elderly are well aware of the problems of undernutrition,
      but not enough of them appear to have a specific protocol to deal with it.
      Earlier screening for undernourishment would be useful. The study also shows the
      important role of nurses' aides in this area. CONCLUSION: Institutions in Haute
      Normandy agree about the need to screen for and treat undernutrition, but their
      interventions are not effective. Better organization and special training of
      health workers could improve this screening and treatment.

PMID- 16614598
TI  - [Advantages and limitations of electroneuromyography for analysis of upper limb
      pain].
AB  - OBJECTIVE: To study the utility of electroneuromyography in analysis of upper
      limb pain as a function of the existence of a diagnostic hypothesis. METHODS: We
      retrospectively compared the consecutive electroneuromyographic examinations
      performed between 1 January and 30 September 2004. All recordings were performed
      by the same examiner in the neurophysiology clinic in the department of neurology
      of Saint-Etienne university hospital UHC at the request of hospital specialists
      or surgeon and private general practitioners. In each examination, at a minimum
      and regardless of the specific situation, motor conduction speed, F waves, and
      sensory conduction speed were recorded for the median nerve and the ulnar nerve
      on the right and left. For the arm in question, needle electromyography explored
      the muscles depending on the C5-T1 roots. RESULTS: In all, 76 patients had ENMG
      examinations, 38 for whom the physician had a diagnostic hypothesis and 38
      patients without. In the case of a diagnosis based on clinical suspicions,
      examination was normal in 73.7% of cases compared with 23.7% when there was a
      clinically based hypothesis (p<0.01). These findings did not vary significantly
      according to the specialization of the referring physician. CONCLUSION:
      Electromyography and nerve conduction studies are useful to confirm a diagnosis
      based on patient reports and clinical data, it is not useful when no diagnosis
      has been suggested.

PMID- 16614599
TI  - [Bosentan for treatment of active digital ulcers in patients with systemic
      sclerosis].
AB  - OBJECTIVES: To describe the effect of bosentan and its dual inhibition of
      endothelin-1 ETA and ETB receptors on digital ulcers in patients with systemic
      sclerosis (SSc). METHODS: Patients receiving bosentan for SSc-related digital
      ulcers were identified in eight centers, and their characteristics and follow-up
      were recorded. RESULTS: Nine (six with diffuse and three with limited cutaneous
      forms of SSc) patients (median age: 54 years) had received bosentan for digital
      ulcers. Complete healing occurred in seven (median time to improvement: 4 weeks).
      Another experienced a significant decrease in the number of ulcers (from 22 to 5)
      in 8 weeks, while one had no improvement. After a median follow-up of 24.3
      months, only one recurrence was observed. Raynaud phenomenon improved in all but
      one patient. DISCUSSION: These data suggest that some patients may benefit from
      bosentan to treat digital ulcers. The short time to healing in these patients
      with rather chronic ulcers argues strongly in favor of its use. These results
      also strengthen the evidence that endothelin-1 plays an important role in the
      vascular manifestations of SSc. CONCLUSION: Bosentan can be effective in the
      treatment of digital ulcers in some SSc patients with SSc, probably especially
      those involving substantial ischemia. Bosentan is not a first-line drug in this
      indication yet and must be carefully used by specialists in SSc. Forthcoming
      results from the international RAPIDS-2 study should clarify the indications for
      bosentan in the treatment of SSc-related digital ulcers.

PMID- 16614600
TI  - [Ventricular septal defects: anatomic, clinical, therapeutic and prognostic
      aspects. 44 cases].
AB  - OBJECTIVES: The aim of this study is to analyze epidemiologic, anatomic, clinical
      and prognostic aspects of ventricular septal defect (VSD) in the pediatric
      population in Morocco. METHODS: This retrospective descriptive study included 44
      consecutive patients admitted to the cardiology B department of Rabat University
      Hospital Center from January 2000 through March 2003. The inclusion criteria
      were: VSD, isolated or associated with other left-right shunt defects, diagnosed
      by transthoracic echocardiography, and hospitalized in the service. RESULTS: VSD
      accounted for 10.6% of the congenital cardiac diseases hospitalized in our
      department. Patients' mean age was 2.25 +/- 2.6 years; the consanguinity rate was
      29%. The primary clinical symptoms were dominated by failure to gain weight
      (84%), exertional dyspnea (82%), and repeated bronchitis (72%). Early
      complications were infundibular stenosis (4 cases), aortic regurgitation (3
      cases), and infectious endocarditis (1 case). Nine children had other
      abnormalities, including 6 with trisomy 21. Echocardiography showed that
      membranous defects were by far the most common type (88%). All patients received
      symptomatic medical treatment. Only 31.7% (n=14) had surgery: 11.3% (n=5) to
      close the hole (corrective) and 20.4% (n=9) for pulmonary artery (palliative)
      banding. After two years of follow-up, those with surgical correction were all
      doing well. CONCLUSION: Surgically closing the VSD is the best way to avoid
      irreversible pulmonary arterial hypertension; banding should be only a temporary
      measure while awaiting corrective surgery.

PMID- 16614601
TI  - [Benzodiazepine withdrawal in subjects on opiate substitution treatment].
AB  - INTRODUCTION: Benzodiazepines are the most widely used psychotropic agents in the
      world. Abuse and dependence are reported in the general population and among drug
      misusers, including those dependent on heroine. Benzodiazepine use by heroine
      users increases their risk of overdose, not only from heroin but also
      substitution drugs such as methadone and more recently buprenorphine. Hence,
      detoxification from benzodiazepines is desirable. OBJECTIVE: The objective of
      this paper was to review the literature and determine the best benzodiazepine
      detoxification procedure for opiate-dependent individuals receiving substitution
      treatment. METHODS: Relevant studies were sought through systematic searches of
      Medline and Toxibase (a database focusing on substance abuse). RESULTS: There
      were fewer controlled studies than expected about benzodiazepine detoxification,
      and all of them excluded subjects who misused opiates or were in opiate
      substitution treatment. The best evidence supports a procedure where the patient
      is switched to a long-lasting benzodiazepine and the dose then tapered by 25% of
      the initial dose each week. Diazepam is the drug most often used in the
      framework. In opiate users, diazepam may raise special problems of misuse, as
      suggested by clinical and epidemiologic studies. Nonetheless, diazepam is the
      only benzodiazepine found to be effective for this withdrawal in controlled
      studies and some studies indicate that unprescribed diazepam use in heroin users
      is sometimes motivated by the desire to alleviate withdrawal symptoms and
      discomfort. CONCLUSION: Although diazepam appears to have potential for abuse,
      the available data does not rule out its therapeutic interest for benzodiazepine
      withdrawal in patients on opiate substitution treatment in an adequate treatment
      setting. Specific studies of this population are needed.

PMID- 16614602
TI  - [MRCP in the diagnosis and management of bile leak caused by blunt liver injury].
AB  - INTRODUCTION: Bile leak is a rare - and difficult to diagnose - complication of
      nonoperative treatment in blunt liver injury. Magnetic resonance
      cholangiopancreatography (MRCP) enables a positive diagnosis and localization of
      the biliary peritoneal fistula. CASE: We report the case of a child with blunt
      liver injury treated nonsurgically and subsequently complicated by bile leak.
      Percutaneous drainage was performed after localization of the biliary fistula
      with MRCP. The patient recovered without adverse sequelae. CONCLUSION: MRCP can
      be successfully used to diagnose abdominal complications of blunt liver injury.
      This minimally invasive approach is the gold standard for management of 80% of
      patients with blunt liver injury.

PMID- 16614603
TI  - [Mandibular resorption, an underdiagnosed manifestation of systemic scleroderma].
AB  - INTRODUCTION: Systemic sclerosis (SSc) is sometimes associated with bone
      resorption that can reach the mandible. CASES: We report here the cases of two
      women (aged 47 and 57 years) with SSc diagnosed 13 and 26 years earlier,
      respectively. Both presented marked mandibular bone resorption. The first had
      prominent interstitial lung disease, and the second, who died within a few
      months, had severe left ventricular dysfunction due to SSc. DISCUSSION:
      Mandibular resorption is a rare but probably underdiagnosed manifestation of SSc.
      In addition to its esthetic effects, it can cause severe disability.

PMID- 16614604
TI  - [Transverse myelitis revealing Hodgkin disease].
AB  - INTRODUCTION: Neurological complications during Hodgkin disease are rare and
      sometimes difficult to diagnose. We report the case of a patient with transverse
      myelitis. CASE: This 32-year-old man was hospitalized on month after onset of
      febrile spastic paraplegia, which was accompanied by progressive deterioration of
      his general condition. Examination revealed a febrile, conscious patient, with
      abolition of the lower-limb tendon reflexes, bilateral Babinski signs, and
      sensitivity at D6-D7. We also noted hepatosplenomegaly, but no peripheral
      adenopathies. Laboratory reports indicated bicytopenia, a major inflammatory
      syndrome and hepatic cytolysis. The computed tomography examination of thorax and
      abdomen showed swelling in deep lymph nodes and the brain MRI showed what
      appeared to be transverse myelitis. The brainstem biopsy was normal; the hepatic
      biopsy showed liver infiltration by Sternberg cells. The patient died rapidly,
      before treatment could begin. DISCUSSION: The variable neurological events
      observed during Hodgkin disease may serve to reveal this disease. Their
      association with a tumor suggests this diagnosis even when the neurological signs
      are nonspecific. They may affect either the brain or the brainstem. Diagnostic
      certainty requires histologic analysis, and prognosis depends on early diagnosis
      and management.

PMID- 16614605
TI  - Treatment of central pontine myelinolysis with thyrotropin-releasing hormone.
AB  - INTRODUCTION: Central pontine myelinolysis (CPM), demyelination of the brain
      stem, is a brain injury apparently due to osmotic forces. There is no consensus
      for its treatment. CASE: We describe here a case of CPM that occurred in a young
      patient after correction of hyponatremia, its treatment by intravenous
      thyrotropin-releasing hormone, and its outcome. DISCUSSION: Although very few
      instances of thyrotropin-releasing hormone treatment for CPM have been described,
      it appears to be effective and well tolerated. Studies are needed to assess its
      real efficacy.

PMID- 16614606
TI  - [Sneddon syndrome].

PMID- 16614607
TI  - [Sarcoidosis mimicking rheumatoid arthritis].

PMID- 16614608
TI  - [Biological therapies: evolution or revolution?].

PMID- 16614609
TI  - [Chikungunya on Reunion Island: chronicle of an epidemic foretold].
AB  - Chikungunya is a viral disease transmitted by a mosquito of the genus Aedes. It
      is currently epidemic on Reunion Island, in the Indian Ocean. It is essentially
      characterized by an influenza syndrome but associated with polyarthralgia and an
      eruption. The disabling and chronic nature of the arthralgia is the most
      remarkable clinical aspect of chikungunya infection. Severe and unusual forms
      have appeared, not previously described in the literature. These forms must be
      studied to determine whether there is a direct relation between the chikungunya
      virus and the severity factors. Treatment is solely symptomatic, combining
      analgesic and/or antiinflammatory agents. There is no vaccine. The epidemic is
      not limited to Reunion: cases of chikungunya have also been reported in
      neighboring islands (Maurice, Seychelles, and Madagascar). Travelers planning to
      visit the region should be counseled.

PMID- 16614610
TI  - [Anti-TNF alpha in the treatment of psoriatic arthritis].
AB  - Psoriatic arthritis is an inflammatory and possibly destructive form of
      arthritis. As in rheumatoid arthritis and ankylosing spondylitis, the use of
      biological therapy in psoriatic arthritis is a therapeutic revolution: both
      articular and cutaneous efficacy have been shown, and some improvement is visible
      on radiography. The benefit-risk ratio will improve when we learn to identify
      more accurately the patients likely to benefit from these treatments.

PMID- 16614611
TI  - [Helicobacter pylori resistance: who needs what treatment?].
AB  - The standard treatment recommended for eradication of Helicobacter pylori is a
      combination of three drugs for seven days: one proton pump inhibitor at a double
      dose and two antibiotics. The high risk of failure - on the order of 30% -
      justifies routine testing to verify eradication after this first treatment.
      Verification is most often conducted with a urea breath test, more rarely by
      endoscopy when endoscopy or gastric histology is otherwise necessary. When
      eradication fails, longer multidrug treatment with different antibiotics is
      proposed. The failure rate after second-line treatment is 9-10%. If a third
      treatment is necessary, bacterial culture is recommended to select antibiotics on
      the basis of the antibiotic susceptibility testing.

PMID- 16614612
TI  - [Misleading "hip" or buttock pain: proximal arteritis or lumbar spinal
      stenosis?].
AB  - Proximal arterial stenosis (bifurcation of the aortic, common iliac and
      especially hypogastric or hip arteries) can cause misleading 'hip' or buttock
      pain (two thirds of these cases involve the area of the trochanter, groin, or
      thigh). Their essential characteristic is that they cause patients to stop
      walking, improve in a minute or two and reappear when the patient starts walking
      again. Neither articular complications nor periarthritis of the hip fit this
      pattern, and physical examination and imaging exclude them. Neurogenic
      intermittent claudication is more difficult to rule out: it is 'often accompanied
      by paresthesia and anteflexion of the trunk to relieve the pain. A radiologic
      image of lumbar canal stenosis alone does not indicate that it is responsible for
      the pain: the stenosis may be asymptomatic and only fortuitously associated with
      the pain. The usual reduction in femoral pulse or ankle pressure index is absent
      if the stenosis is located on the hypogastric or gluteal artery and there is not
      substantial damage to the aorta-iliac axis. Arterial stenosis is confirmed by
      Doppler ultrasound. Arteriography is an examination performed during treatment,
      to guide angioplasty. It is indicated when medical treatment fails, as it
      frequently does.

PMID- 16614613
TI  - [Intraductal papillary mucinous tumors of the pancreas].
AB  - Reports of intraductal papillary mucinous tumors of the pancreas have become
      substantially more frequent in the literature in the past several years. This
      increased prevalence is due, among other things, to improved screening
      techniques, especially high-resolution spatial imaging. These tumors are
      characterized by proliferation of the intraductal epithelium, mucin production,
      and ductal dilatation. They grow slowly. Their potential for malignancy is high
      (although the precise risk remains difficult to assess), but their prognosis,
      when identified during the first stage of neoplastic transformation (before
      invasion), is far better than that of 'pancreatic ductal adenocarcinoma. Early
      diagnosis allows patients to be treated before carcinomatous degeneration.
      Specific diagnosis makes it possible to define an appropriate treatment strategy 
      either surgery or monitoring, especially when only the intralobular ducts are
      affected. In that case, the risk of malignant degeneration is much lower than
      with lesions in the pancreatic duct or in combined forms.

PMID- 16614614
TI  - [Adding aspirin to clopidogrel in secondary prevention of ischemic stroke: no
      significant benefits. Results of the Match study].
AB  - Antiplatelet therapy is the reference treatment for secondary prevention after
      noncardioembolic ischemic stroke. The main aim of the Match study was to compare
      the combination of aspirin (75 mg) and clopidogrel (75 mg) with clopidogrel (75
      mg) alone in secondary prevention after recent ischemic stroke or transcient
      ischemic attack in high-risk patients. The incidence of the composite principal
      endpoint (ischemic stroke, myocardial infarction, vascular death, or acute
      ischemic event causing hospitalization) was 15.7% at 18 months in patients in the
      aspirin-clopidogrel arm, compared with 16.7% in the placebo-clopidogrel arm. The
      relative risk reduction (6.4%) was not significant (95%CI, -4.6 to 16.3;
      p=0.244). Patients receiving the combination of aspirin and clopidogrel had more
      life-threatening bleeding than those treated by clopidogrel alone (2.6% vs 1.3%;
      95%CI, 1.3 to 2.6; p<0.001). Recruitment that began too late and an over-selected
      population, with overrepresentation of patients with diabetes and small vessel
      disease in particular, may partly explain these negative results.

PMID- 16614615
TI  - [Pulmonary damage during polymyositis and dermatomyositis: interstitial lung
      disease].
AB  - Interstitial lung disease is a serious complication of
      polymyositis/dermatomyositis and leads to death from chronic respiratory
      insufficiency in 30 to 66% of cases. It is a criterion of poor prognosis in these
      disorders. Its onset occurs at variable points in the course of
      polymyositis/dermatomyositis, and precedes them in half of all cases.
      Presentation may also vary: acute (25%), insidious (60%), or infraclinical,
      discovered fortuitously (15%). The examinations of choice for early screening are
      high-resolution computed tomography (CT) and pulmonary function tests, which
      should be performed during the initial work-up and during ongoing surveillance.
      Moreover, high-resolution CT also makes it possible to determine the type of
      histologic lesions in the interstitial lung disease. Today, diagnosis of this
      disease does not generally require histological confirmation; nonspecific
      interstitial lung disease seems to be the most common histologic form of lung
      damage in polymyositis/dermatomyositis (40 to 80%). Anti-Jo1 antibodies are a
      sensitive marker of interstitial lung disease during
      polymyositis/dermatomyositis, and close surveillance of lung function is
      recommended in patients with these autoantibodies. Systematic testing for them is
      also justified in patients with apparently idiopathic interstitial lung disease,
      to rule out underlying polymyositis/dermatomyositis. No clear treatment protocols
      have been established for interstitial lung disease during
      polymyositis/dermatomyositis. Corticosteroid treatment is the first choice. Its
      combination with cyclophosphamide may be most effective in corticosteroid
      resistant forms of polymyositis/dermatomyositis, especially when begun early; it
      may also be appropriate to begin corticosteroids as soon as factors predicting
      poor prognosis are detected.

PMID- 16614616
TI  - [Insulin in the treatment of ischemic stroke].
AB  - Hyperglycemia is correlated with poor prognosis in ischemic strokes and also
      increases the risk of hemorrhagic transformation after thrombolysis. The toxicity
      of hyperglycemia, already well established in animals, is beginning to be clear
      for humans. On the other hand, the beneficial effect of insulin remains
      controversial in animals and has never been demonstrated in humans. Preliminary
      data, which suggest that the speed and quality of glycemic control may be
      decisive in the efficacy of treatment, merit testing in a randomized trial.

PMID- 16614618
TI  - [Treating immune-mediated diseases].

PMID- 16614617
TI  - [Antipsychotic drugs and cardiovascular safety: need for monitoring the QT
      interval].
AB  - Torsades de pointes (TdP), a form of ventricular arrhythmia that can cause
      ventricular fibrillation and sudden death, may occur during prolongation of the
      QT interval. QT prolongation has recently been reported with antipsychotic drugs.
      Physicians should be able to obtain a corrected measurement of the QT interval.
      QT is measured from the beginning of the QRS complex to the end of the T wave
      (QTm). This value must then be corrected to take heartbeat into account. The most
      common formula in current use is Bazett's. In practice, a QTc interval value
      greater than 500 ms indicates an increased risk of TdP. Safe combinations of
      antipsychotic drugs have been recommended by the French drug agency (Agence
      francaise de securite sanitaire des produits de sante). Many other drugs,
      including psychotropic drugs such as tricyclic antidepressants, can prolong the
      QT interval. Combinations of these medications with one another, with
      antipsychotic medications, or with other concomitant factors, such as
      hypokalemia, also increase the risk. TdP is most often diagnosed only after
      observing QT prolongation. This underlines the need to monitor QT intervals
      attentively to prevent the risk of cardiac arrhythmia in patients treated with
      antipsychotic drugs.

PMID- 16614619
TI  - [New therapeutic approaches to autoimmune diseases].
AB  - Over the past decade, new biological therapies have been developed to treat
      systemic autoimmune diseases. These new treatments, which target various steps of
      the immune response, include: B lymphocyte (BL) inhibitors, such as anti-CD20
      monoclonal antibodies, BlyS antagonists, and tolerogens that inhibit specific BLs
      that produce pathogenic antibodies; inhibitors of costimulation between antigen
      presenting cells and T lymphocytes (TL), such as monoclonal antibodies against
      CD40 ligand and CTLA4-Ig (abatecept); TL antagonists, which can inhibit
      proliferation of autoreactive T cells; cytokine antagonists; chemokine and
      adhesin antagonists, which inhibit trafficking of immunocompetent cells to target
      organs. These new approaches are based on a deeper understanding of the
      autoimmune response.

PMID- 16614620
TI  - [Indications for intravenous immunoglobulins].
AB  - Intravenous immunoglobulins (IgIV) are therapeutic preparations of polyclonal
      human IgG, obtained from a pool of plasma from more than 1000 healthy donors.
      This article discusses only some of the recognized indications (Group I) and some
      of those currently under evaluation (Group II) for the treatment of autoimmune
      and systemic inflammatory diseases. Perspectives for IgIV use are approached
      through three diseases, each providing a different model of immune system
      modulation: ocular cicatricial pemphigoid, where an autoimmune reaction is
      modulated; alloimmunization of chronic hemodialysis patients, where
      alloreactivity can be modulated; and streptococcal toxic shock, where anti
      infectious immunity may be modulated.

PMID- 16614621
TI  - [Multifocal motor neuropathy with persistent conduction blocks. A chronic immune
      mediated neuropathy].
AB  - Multifocal motor neuropathy with persistent conduction blocks was first
      specifically identified in 1986. Its major criterion is conduction blocks in
      motor nerves only. Clinically, this is a multifocal, thus asymmetric, neuropathy
      that begins and predominant touches upper limbs; it especially affects men after
      the age of 50 years and has a chronic course with relapses. Approximately 40-50%
      of patients also have IgM serum antibodies directed against GM1 ganglioside.
      There are no other laboratory criteria, although moderately high protein levels
      are found in cerebrospinal fluid. Its course is unpredictable, because the
      neuropathy may remain limited to one or two motor nerves or extend progressively
      to all the motor nerves of all four limbs. In general, there is no damage to
      sensory or cranial nerves or to the autonomic or central nervous systems.
      Intravenous polyvalent immunoglobulins at high doses are remarkably effective in
      the short term in 70 to 80% of cases. Corticosteroids and plasma exchange are
      generally ineffective and may aggravate the neuropathy. The long-term efficacy of
      intravenous immunoglobulins in delaying motor decline and axon loss in the
      affected motor nerves is controversial. No information is currently available
      about the long-term efficacy of other immunomodulatory treatment.

PMID- 16614622
TI  - [Hepatocellular carcinoma, appearance on computed tomography].

PMID- 16614624
TI  - Nonopportunistic neurologic manifestations of the human immunodeficiency virus:
      an Indian study.
AB  - CONTEXT: HIV-1 is a neurotropic virus. In a resource-limited country such as
      India, large populations of affected patients now have access to adequate
      chemoprophylaxis for opportunistic infections (OIs), allowing them to live
      longer. Unfortunately the poor availability of highly active antiretroviral
      therapy (HAART) has allowed viral replication to proceed unchecked. This has
      resulted in an increase in the debilitating neurologic manifestations directly
      mediated by the virus. OBJECTIVE: The main objective of this study was to
      identify and describe in detail the direct neurologic manifestations of HIV-1 in
      antiretroviral treatment (ART)-naive, HIV-infected patients (excluding the
      neurologic manifestations produced by opportunistic pathogens). DESIGN: Three
      hundred successive cases of HIV-1 infected, ART-naive patients with neurologic
      manifestations were studied over a 3-year period. Each case was studied in detail
      to identify and then exclude manifestations due to opportunistic pathogens. The
      remaining cases were then analyzed specially in regard to their occurrence and
      the degree of immune suppression (CD4+ cell counts). SETTINGS AND PATIENTS: The
      study was carried out in an apex, tertiary, referral care center for HIV/AIDS in
      India. All patients were admitted for a detailed analysis. No interventions were
      carried out, as this was an observational study. RESULTS: Of the 300 cases, 67
      (22.3%) had neurologic manifestations due to the direct effects of HIV-1. The HIV
      infection involved the neuroaxis at all levels. The distribution of cases showed
      that the region most commonly involved was the brain (50.7%). The manifestations
      included stroke syndromes (29.8%), demyelinating illnesses (5.9%), AIDS dementia
      complex (5.9%), and venous sinus thrombosis (4.4%). The other manifestations seen
      were peripheral neuropathies (35.8% of cases), spinal cord pathologies (5.9% of
      cases), radiculopathies (4.4% of cases), and a single case of myopathy. The onset
      of occurrence of these diseases and their progression were then correlated with
      the CD4+ cell counts. CONCLUSIONS: HIV infection is responsible for a large
      number of nonopportunistic neurologic manifestations that occur across a large
      immune spectrum. During the early course of the disease, the polyclonal
      hypergammaglobulinemia induced by the virus results in demyelinating diseases of
      the central- and peripheral nervous systems (CNS and PNS). As the HIV infection
      progresses, the direct toxic effects of the virus unfold, directly damaging the
      CNS and PNS, resulting in protean clinical manifestations.

PMID- 16614625
TI  - The safety of psychotropic drug use during pregnancy: a review.
AB  - A substantial number of women of childbearing age are prescribed psychotropic
      drugs, and because nearly 50% of pregnancies are unplanned, many women are still
      taking them upon becoming pregnant. This article reviews the various classes of
      psychotropic drugs that are commonly used to treat psychiatric disorders-
      antidepressants, benzodiazepines, antipsychotics, antiepileptics, lithium and
      monoamine oxidase (MAO) inhibitors--in terms of their safety during pregnancy.
      Evidence-based information from epidemiologic studies indicates that most
      psychotropic drugs are relatively safe for use during pregnancy. There is also an
      increasingly large body of evidence-based information in the literature
      indicating that it may be more harmful to both the mother and her baby if she is
      not treated appropriately when suffering from a severe psychiatric disorder.
      Therefore, it is important for women with psychiatric disorders and their
      healthcare providers to have access to evidenced-based information about the
      safety of these drugs when taken during pregnancy to ensure that women make an
      informed decision as to whether they should continue with the pharmacotherapy
      they have been using to treat their condition.

PMID- 16614626
TI  - Sciatic nerve block after total knee replacement.

PMID- 16614627
TI  - Is there a place for medical blogs in a medical media company?

PMID- 16614628
TI  - Readers' responses to "doctors and patients working together".

PMID- 16614630
TI  - Management strategies of dyslipidemia in the elderly: 2005.
AB  - During the past 3 years, the treatment of dyslipidemia has evolved significantly.
      The impact of recent trial data on management strategies in older patients is
      especially important, because the elderly segment of the US population continues
      to grow. Several clinical trials have been completed since the publication of the
      National Cholesterol Education Program (NCEP) Adult Treatment Panel III
      guidelines were published in 2001. Recent trial data strongly support the use of
      lipid-lowering therapy in the elderly population. Although therapeutic lifestyle
      changes remain highly important, supplementation with lipid-lowering therapy has
      been shown to reduce the risk of cardiovascular events in both primary and
      secondary prevention models. Compelling data noted from recent clinical trials
      have prompted the NCEP to publish an updated report that addresses the
      significant interim developments.

PMID- 16614631
TI  - Case files from the Bellevue Hospital Center at New York University--lipoatrophy
      following long-term antiretroviral therapy.

PMID- 16614632
TI  - Are healthcare professionals advising obese patients to lose weight? A trend
      analysis.
AB  - BACKGROUND: During the past 20 years, adult obesity rates have doubled in the
      United States. The National Institutes of Health (NIH) issued guidelines in 1998
      recommending that healthcare professionals advise obese patients to lose weight.
      We examined trends in physician counseling for weight loss during 1994-2000,
      characteristics of obese adults receiving advice to lose weight in 2000, and the
      association in 2000 between receiving advice and attempting to lose weight.
      METHODS: We analyzed 1994, 1996, 1998, and 2000 data from the Behavioral Risk
      Factor Surveillance System (BRFSS), a state-based telephone survey of
      noninstitutionalized adults from 48 states and the District of Columbia. We
      limited the analysis to obese respondents who had visited physicians for a
      routine medical checkup during the previous 12 months (n = 61,968). RESULTS:
      Among obese patients, the proportion who received advice to lose weight decreased
      from 42.3% (se = 0.79) in 1994 to 40.3% (se = 0.55) in 2000. We observed declines
      in receipt of advice for almost all subgroups. Respondents in the youngest and
      oldest age groups and those without health insurance had the largest significant
      declines. Patients who reported receiving advice to lose weight had 2.8 the odds
      of trying to lose weight as those who did not receive advice (95% confidence
      interval, 2.5, 3.2). CONCLUSION: Despite the 1998 NIH guidelines and increases in
      morbid obesity, the proportion of obese persons who reported being counseled by a
      healthcare professional has declined slightly. Because counseling might be
      associated with weight loss attempts, barriers to counseling need to be
      identified and addressed.

PMID- 16614633
TI  - Grand rounds in gastroenterology from Baylor College of Medicine. A pustular skin
      rash in a woman with 2 weeks of diarrhea.

PMID- 16614634
TI  - One more reader responds to "boxing should be banned in civilized countries-
      round 4".

PMID- 16614635
TI  - A reader responds to "the crisis in America's laboratories: it's every
      physician's business".

PMID- 16614636
TI  - Women in medicine.

PMID- 16614637
TI  - Eye problem following foot surgery--abducens palsy as a complication of spinal
      anesthesia.
AB  - BACKGROUND: Paralysis of abducens nerve is a very rare complication of lumbar
      puncture, which is a common procedure most often used for diagnostic and
      anesthetic purposes. CASE REPORT: A 38-year-old man underwent surgery for a left
      hallux valgus while he was under spinal anesthesia. On the first postoperative
      day, the patient experienced a severe headache that did not respond to standard
      nonsteroidal anti-inflammatory medication and hydration. During the second
      postoperative day, nausea and vomiting occurred. On the fourth postoperative day,
      nausea ceased completely but the patient complained of diplopia. Examination
      revealed bilateral strabismus with bilateral abducens nerve palsy. His diplopia
      resolved completely after 9 weeks and strabismus after 6 months. CONCLUSION:
      Abducens palsy following spinal anesthesia is a rare and reversible complication.
      Spinal anesthesia is still a feasible procedure for both the orthopaedic surgeon
      and the patient. Other types of anesthesia or performing spinal anesthesia with
      smaller diameter or atraumatic spinal needles may help decrease the incidence of
      abducens palsy. Informing the patient about the reversibility of the complication
      is essential during the follow-up because the palsy may last for as long as 6
      months. Special attention must be paid to patient positioning following the
      operation. Recumbency and lying flat should be accomplished as soon as possible
      to prevent cerebrospinal fluid leakage and resultant intracranial hypotension.
      This becomes much more important if the patient has postdural puncture headache.

PMID- 16614638
TI  - Abducens palsy following spinal anesthesia: mechanism, treatment, and anesthetic
      considerations.

PMID- 16614640
TI  - Omega-3 fatty acids: recommendations for therapeutics and prevention.

PMID- 16614641
TI  - A life-threatening multilocalized hidradenitis suppurativa case.
AB  - The patient was a 38-year-old man. He had been suffering from hidradenitis
      suppurativa (HS) for approximately 20 years. He had active lesions at both
      axillas, hip, scrotum, and perineum, and inactive lesions located behind the
      ears, lower abdomen, and posterior neck. He was monitored and treated at
      different branches; he continuously used antibiotics and was given steroids at
      times. Antibiotic resistance developed subsequently. His general situation was
      bad; vital signs were poor; and he was in a state of sepsis and preshock, so this
      case was regarded as life-threatening. Total excision was performed first on the
      lesion at the right axilla, then on the lesion at the left axilla, and the
      parascapular fasciocutaneous flap was reversed. A skin graft was applied to the
      triangular defect on the scapula. No relapse occurred. Then the lesions at the
      hip were managed. Broad excision was used twice with the patient under general
      anesthesia; because the lesions spread to the retrococcygeal and gluteal muscles,
      coccyx resection and partial gluteal muscle resection were implemented. The
      defect was eliminated with a progressive flap. At the intergluteal sulcus, small
      lesions emerging at the median line were debrided with the patient under local
      anesthesia, and together with secondary recovery, the disease was completely
      managed. Lesions at the perineum and scrotum and at both inguinal areas were
      broadly excised and grafted. No lesion has relapsed so far. One year later,
      Hodgkin's lymphoma was diagnosed, and the patient was treated with
      chemoradiotherapy easily, because there was no infective focus. The disease is in
      remission now. The patient weighs 110 kg, is healthy, and is working again.

PMID- 16614642
TI  - The healthcare system is also a patient!

PMID- 16614643
TI  - Readers' responses to "thought for food: 2400-year-old advice for today's
      worldwide weight crisis".

PMID- 16614644
TI  - MRI replaces CT for stroke evaluation.

PMID- 16614646
TI  - Approaching cardiac arrhythmias in the elderly patient.

PMID- 16614645
TI  - Case report: A large extramedullary granulocytic sarcoma as the initial
      presenting feature of chronic myeloid leukemia.
AB  - Granulocytic sarcomas (chloromas) are rare extramedullary tumors consisting of
      primitive granulocytic cells. They arise de novo, or are associated with other
      hematologic disorders such as acute myeloid leukemia, myelodysplastic syndrome,
      or myeloproliferative disorders. We report here on a case of a 62-year-old woman
      who presented with a large swelling in her right groin and leg. The mass was
      confirmed by biopsy to be a granulocytic sarcoma. Bone marrow examination showed
      mild hypercellularity but no evidence of increase in blast count. However,
      cytogenetic examination of the marrow showed t(9;22), indicating an unexpected
      diagnosis of chronic myeloid leukemia.

PMID- 16614647
TI  - Atypical manifestations of gastroesophageal reflux disease.

PMID- 16614648
TI  - Increasing diversity in the medical workforce is one solid way to prevent
      disparities in healthcare.

PMID- 16614649
TI  - Reader responds to "did your genes give you that sore throat?".

PMID- 16614650
TI  - Reader responds to letter to the editor "doctors and patients working together".

PMID- 16614652
TI  - We were wrong about "crack babies": are we repeating our mistake with "meth
      babies"?

PMID- 16614653
TI  - On the futility of dieting.

PMID- 16614654
TI  - Clinical case conferences from the University of Pennsylvania School of Medicine-
      a 58-year-old man with dysphagia.

PMID- 16614655
TI  - Localized epidermolytic hyperkeratosis of the female genitalia: a case report and
      review of an underappreciated disorder of women.
AB  - Epidermolytic hyperkeratosis (EHK) is a distinct pathologic entity that may
      present as a generalized congenital disorder. A localized form occurring only
      upon the female genitalia may not be well appreciated by clinicians dealing with
      women. EHK of the female genitalia is a rare diagnosis, with just 6 cases
      reported within the indexed literature. Clinically, it may resemble condyloma,
      although involvement of human papillomavirus has never been demonstrated.
      Providers unfamiliar with this entity may be further confused by reports of the
      histopathologic features. Herein, we describe a case and review the literature
      with respect to EHK of the female genitalia. Familiarity with this condition is
      desirable, as confusion with condyloma is likely, yet the prognosis is decidedly
      different.

PMID- 16614657
TI  - Readers' responses to "it is time for marijuana to be reclassified as something
      other than a schedule I drug".

PMID- 16614658
TI  - How to write a medical paper to get it published in a good journal.

PMID- 16614659
TI  - Medicaid: a vision for the next 40 years.

PMID- 16614662
TI  - Management of idiopathic intracranial hypertension in pregnancy.

PMID- 16614661
TI  - Noninvasive diagnosis of liver fibrosis in patients with chronic hepatitis C.

PMID- 16614663
TI  - Response to diet and metformin in women with idiopathic intracranial hypertension
      with and without concurrent polycystic ovary syndrome or hyperinsulinemia.

PMID- 16614664
TI  - Choice of therapy and mode of delivery in idiopathic intracranial hypertension
      during pregnancy.
AB  - Benign intracranial hypertension (BIH) or idiopathic intracranial hypertension
      (IIH) is a rare disorder of unknown etiology that is most often seen in obese
      women of reproductive age (19.3/100,000) and is reported only occasionally during
      pregnancy. Both pregnancy and exogenous estrogens are thought to promote IIH or
      worsen it. It can occur in any trimester during pregnancy, and the visual outcome
      is the same as for nonpregnant patients with IIH. There is no increase in fetal
      wastage; therapeutic abortion to limit its progression is not indicated, and
      subsequent pregnancies do not increase the risk of recurrence. Most therapies
      used during the nonpregnant state can also be used during pregnancy. The aim of
      treatment is to preserve vision and improve symptoms. Treatments include
      analgesics, diuretics, steroids, and serial lumbar punctures. When medical
      therapy fails, surgical procedures need to be considered. Although this condition
      has been reviewed often, the issue of mode of delivery, especially when
      papilledema has not resolved, is unclear. We report on 3 women with IIH during
      pregnancy and review the choice of therapy and mode of delivery.

PMID- 16614665
TI  - Readers' responses to "are 80 hours a week enough to train a surgeon?".

PMID- 16614667
TI  - 1918 flu deaths give insight to avian virus.

PMID- 16614668
TI  - Thought for food, part 2: a great weight-loss supplement?

PMID- 16614669
TI  - So what is a sham peer review?

PMID- 16614671
TI  - Optimal initiation of insulin in type 2 diabetes.
AB  - Treatment goals for glycemic control in patients with type 2 diabetes are often
      not achieved or are difficult to maintain as the disease progresses. Too often,
      insulin therapy is either delayed or is suboptimal. We discuss how the
      introduction of new insulin analogs may help overcome some of the barriers to
      insulin use. If combination therapy with oral agents does not achieve glycemic
      control, the addition of a once-daily intermediate- or long-acting insulin is a
      simple and highly effective strategy for initiating insulin. If glycemic control
      is still not achieved, a short- or rapid-acting insulin may be needed prior to
      meals (basal-prandial approach). A patient's baseline glycosylated hemoglobin
      (A1C) can guide whether glycemic control can be achieved with basal insulin or
      will require basal-prandial replacement. In addition to A1C, a patient's age,
      lifestyle, competence, personal preferences, and comorbidities can be used to
      help determine the choice of insulin therapy.

PMID- 16614673
TI  - A response to the letter by NAMS regarding the role of testosterone therapy in
      postmenopausal women.

PMID- 16614674
TI  - Who gets shot? Firearms and the doctor.

PMID- 16614675
TI  - Are we really better off with HIPAA?

PMID- 16614677
TI  - Let's all remember that resident physicians are learners first.

PMID- 16614676
TI  - Opioids and treatment of chronic pain: understanding pain patterns and the role
      for rapid-onset opioids.
AB  - Chronic pain is a frequent medical condition that has a significant impact on
      patients, including their ability to function and enjoy life. In addition,
      chronic pain has a substantial economic impact on the workplace and costs of
      healthcare. Although not without controversy, opioids are effective in the
      treatment of noncancer chronic pain. Understanding the pattern of temporal
      variations in a patient's pain is important in developing an opioid-based
      treatment plan. By understanding those times of day and activities that may
      precipitate severe episodes of pain, tailored opioid treatment plans can be
      developed that manage pain, improve patient functionality, and minimize side
      effects. Recently developed rapid-onset opioid formulations should be considered
      as part of the chronic pain management strategy in addition to more traditional
      long-acting, sustained-release formulations and short-acting, normal-release
      formulations.

PMID- 16614678
TI  - Misdiagnosis of overweight and underweight children younger than 2 years of age
      due to length measurement bias.
AB  - CONTEXT: Accurate determination of the length of very young children is important
      because weight-for-length standards are used to assess both under- and
      overweight. Clinical measurements of length, which usually involve a paper-and
      pencil method, may often be inaccurate in children younger than 2 years.
      OBJECTIVE: To compare length measured by the conventional clinical paper-and
      pencil method with length measured by the research standard recumbent length
      board method in a sample of children under 2 years of age. METHODS: Research
      assistants measured 160 children 0 through 23 months of age using the recumbent
      length-board method, and clinical staff measured the same children using the
      paper-and-pencil method. To assess the relationship between the research and
      clinical length measurements, we used ordinary least squares regression. RESULTS:
      We found a strong linear relationship between the 2 measures of length (R2 =
      0.98). The paper-and-pencil method systematically overestimated length in
      children under 2 years of age. A fitted regression equation estimated that the
      research standard length was 95.3% of the clinical measurement plus 1.88 cm. Over
      the entire age span, the mean (SD) difference between clinical and research
      measurements was 1.3 (1.5) cm. CONCLUSIONS: Using the paper-and-pencil method can
      lead to underestimates of overweight and exaggerated estimates of thinness. To
      improve the accuracy of length measurement, medical providers should use
      standardized procedures with a recumbent length board to measure children under 2
      years of age, at least for children whose initial paper-and-pencil measurement of
      length puts them at one extreme or the other.

PMID- 16614680
TI  - Reader's response to "coercive restraint therapies: a dangerous alternative
      mental health intervention".

PMID- 16614679
TI  - Multifactorial etiology of cervical cancer: a hypothesis.
AB  - Cancer of the cervix is the second most common life-threatening cancer among
      women worldwide, with incidence rates ranging from 4.8 per 100,000 women per year
      in the Middle East to 44.3 per 100,000 in East Africa. Epidemiologic and clinical
      data demonstrate that human papillomaviruses (HPV), especially HPV-16 and HPV-18,
      play at least a major if not a necessary role in the etiology of cervical cancer.
      However, many investigators acknowledge that HPV is not sufficient to induce
      cervical cancer and that a multifactorial etiology is likely. HPV can be found in
      a growing proportion of patients with cervical cancer, approaching 100%, but is
      not yet found in every patient with disease. Other factors, such as herpes
      simplex virus type 2 infections, cigarette smoking, vaginal douching, nutrition,
      and use of oral contraceptives, have been proposed as contributing factors. In
      the first half of the 20th century, Peyton Rous and colleagues demonstrated the
      joint action of tars and Shope papillomavirus to consistently induce squamous
      cell carcinomas in rabbits. Using the Rous model as a prototype, one might
      hypothesize that some cases of cervical cancer arise from an interaction between
      oncogenic viruses and cervical tar exposures. Cervical tar exposures include
      cigarette smoking, use of tar-based vaginal douches, and long years of inhaling
      smoke from wood- and coal-burning stoves in poorly ventilated kitchens.

PMID- 16614682
TI  - Good medicine is efficient medicine.

PMID- 16614683
TI  - There have been inadequate warnings that erectile dysfunction drugs can cause
      blindness.

PMID- 16614684
TI  - Stress urinary incontinence in women: diagnosis and medical management.
AB  - Stress urinary incontinence (SUI) is the most common form of urinary incontinence
      in women and is associated with high financial, social, and emotional costs. The
      history and physical examination can identify most patients with a significant
      stress incontinence component without the need for urodynamic testing. A variety
      of pharmacologic agents have been used off-label, but an evidence-based
      pharmacologic treatment has not been readily available. The development of a
      selective serotonin and norepinephrine reuptake inhibitor will add a potentially
      useful drug to the primary care physician's practice for treating female patients
      with SUI. In August 2004, a selective serotonin and norepinephrine reuptake
      inhibitor, duloxetine, became the first medication approved for the treatment of
      women with moderate to severe SUI throughout the European Union. As of November
      2005, however, duloxetine has not been approved for the treatment of SUI in the
      United States.

PMID- 16614685
TI  - Macrolide-resistant Streptococcus pneumoniae: clinical implications for the
      empiric treatment of community-acquired respiratory tract infections.

PMID- 16614687
TI  - Readers' responses to "in the wake of Katrina: a surgeon's first-hand report of
      the New Orleans tragedy".

PMID- 16614688
TI  - Patient-centered primary care: it can happen here.

PMID- 16614689
TI  - The cost of marginal medicine is too high.

PMID- 16614690
TI  - SCOPE meets SCOPE in the gastrointestinal tract.

PMID- 16614691
TI  - Lysine clonixinate vs naproxen sodium for the acute treatment of migraine: a
      double-blind, randomized, crossover study.
AB  - BACKGROUND AND OBJECTIVES: The process of inflammation is crucial in migraine,
      and several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the
      treatment of migraine attacks. Despite their efficacy, the routine use of NSAIDs
      is limited by side effects as well as incomplete efficacy in some patients. Among
      the available options, lysine clonixinate (LC) and naproxen sodium (NS) have
      proved effective in migraine. The aim of this study was to compare the efficacy
      and tolerability of oral formulations of LC and NS in the treatment of moderate
      or severe migraine attacks, with a double-blind, crossover design. METHODS:
      Seventy subjects (62 women, 8 men) between ages 18 and 71 years (mean age, 41)
      with migraine according to the criteria of the International Headache Society
      were prospectively enrolled. The patients were randomized into 2 groups and each
      participant treated 2 migraine attacks. Group 1 treated the first attack with LC
      and the second attack with NS. Group 2 treated 2 attacks in a counterbalanced
      order. Doses were 250 mg of LC or 550 mg of NS, which were encapsulated for equal
      appearance. Headache intensity, nausea, photophobia, and side effects were
      evaluated at baseline, 1 hour, and 2 hours after drug administration. Rescue
      drugs were allowed after 2 hours for those who didn't respond, and this was also
      compared between groups. RESULTS: Sixty patients (54 women, 6 men) completed the
      study. At 1 hour, 13.6% patients who used LC were pain-free compared with 11.9%
      who used NS (P = .78). At 2 hours, 35.6% patients who took LC and 32.2% who took
      NS were pain-free (P = .69). At baseline, 52.5% of the patients randomized to
      group 1 reported nausea, compared with 33.9% in group 2, and both drugs
      eliminated nausea: At both 1 hour and 2 hours, nausea diminished significantly
      for those taking LC, but only after 2 hours for those who took NS (P < .0001).
      Both drugs eliminated photophobia at 1 hour and 2 hours; however, LC was superior
      to NS in reducing photophobia at 2 hours (P = .027). Ten patients who took LC and
      8 who took NS required rescue drugs after 2 hours. Twelve patients who used LC
      and 16 who took NS reported side effects. COMMENTS: Although this study did not
      include a placebo arm, which impairs any definitive efficacy claims, we found LC
      and NS to be similarly effective and well tolerated in patients presenting
      moderate or severe attacks of migraine.

PMID- 16614692
TI  - Gastroduodenal obstruction from Morgagni hernia in an elderly patient.

PMID- 16614693
TI  - Screening for at-risk drinking should be as routine as taking a vital sign.

PMID- 16614694
TI  - Are the authors listed on that paper really the authors?

PMID- 16614695
TI  - Leech bite: a rare gynecologic emergency.
AB  - Vaginal bleeding as the result of a leech bite is a rare occurrence. We report 2
      cases of vaginal bleeding in young girls that resulted from a leech bite and
      required treatment. Clinical presentation and management for young girls is
      described. Health professionals working in rural areas where leech infestation is
      common should be aware that children are at risk for leech bites in the genital
      region; a high index of suspicion is of great help to make an early diagnosis and
      ensure prompt treatment.

PMID- 16614696
TI  - Giant supratrigonal vesicocervicovaginal fistula--a case report.
AB  - Vesicovaginal fistula (VVF) is prevalent in the developing world, with recent
      estimates suggesting that 2 million women live with fistula, mainly in sub
      Saharan Africa and South Asia. VVF is associated with urogenital infections and
      ammonia dermatitis, and the psychosocial ramifications may be devastating, as
      women may be socially isolated from their families and community. VVF also
      remains a challenging condition for the gynecologic surgeon. We present a case of
      a giant supratrigonal VVF repaired using an abdominal (suprapubic)
      transperitoneal transvesical approach.

PMID- 16614699
TI  - Health policy year in review: a mixed bag.

PMID- 16614700
TI  - Experimental bladder carcinogenesis-rodent models.
AB  - Several rodent models of bladder cancer development have been established. The
      aim of this review article is to provide a critical assessment of different
      animal models available for the study of bladder carcinogenesis, its
      chemoprevention and therapy. All, except for transgenic and knockout animals,
      require 8-12 months experimental periods in order to generate a high yield of
      neoplasias. Spontaneous bladder tumor models are extremely rare. The significance
      of the results from animal experiments is dependent upon the selection of a
      suitable animal model. There are no rules regarding the choice of a model, it is
      however very useful to have knowledge of relevant comparative medical aspects
      concerning this subject. We describe chemical carcinogens most commonly used to
      induce bladder cancer, pellet implantation and urinary calculi, agents that
      promote bladder cancer, and irradiation. We also evaluated other tools such as
      cell cultures, tumor implantation and transgenic models for bladder cancer, that
      have been developed to study the process. The review considers how several
      imaging techniques can be applied to study rodent bladder carcinogenesis.

PMID- 16614701
TI  - Cell-cell contact mediated signalling - no fear of contact.
AB  - Cancer research with sole focus on the cancer cell and possibly growth factors
      cannot faithfully reproduce the environmental interaction, such as adhesion of
      tumor cells to e.g. stromal cells, which may determine the response of these
      tumors to therapy. Methodologically cell adhesion studies are often difficult
      since complete but careful detachment is the prerequisite for most signal
      transduction assays. We describe for the first time an alternative method for the
      co-incubation of multiple myeloma cells on long term primary bone marrow stromal
      cultures using the bone marrow stromal cell line HS-5. The methods are precisely
      described, advantages and disadvantages are discussed, and troubleshooting
      advises are given.

PMID- 16614702
TI  - Differential effect of selected methylxanthine derivatives on radiosensitization
      of lung carcinoma cells.
AB  - AIM: Using caffeine as a reference derivative, this study was performed to
      investigate how other methylxanthine derivatives, theophylline, 3-isobutyl
      methylxanthine and 1,3-dipropyl-7-methylxanthine, sensitize cells to radiation by
      modifying cell cycle checkpoints and inducing the apoptotic response. The effect
      of the methylxanthine derivatives was studied in response to gamma and
      ultraviolet radiation in a human large cell lung carcinoma cell line, null for
      p53, a normal lung epithelial cell line and the large cell lung carcinoma cell
      line stably transfected with p53. METHODS: Effects of theophylline, 3-isobutyl
      methylxanthine and 1,3-dipropyl 7-methylxanthine on cell-radiosensitization in
      comparison to caffeine tested by clonogenic survival assay, MTT assay, ELISA
      based apoptotic assay, flow cytometry, caspase-3 activity, TUNEL assay, and
      western blot analysis. RESULTS: All the derivatives, except 3-isobutyl
      methylxanthine, increased tumor cell sensitization to radiation by inducing
      apoptosis in the p53-null lung cancer cell line. The pattern of cell cycle
      progression revealed that these derivatives increased the number of cells in G1
      phase by abrogating the G2/M checkpoint, directing the cells to apoptose through
      a p53-independent mechanism. In contrast, 3-isobutyl-methylxanthine was more
      potent than the other derivatives in radiosensitization of normal lung epithelial
      cells and the lung carcinoma cells stably transfected with wild-type p53. IBMX
      increased p53 protein level more than caffeine in lung carcinoma cells stably
      transfected with wild-type p53. CONCLUSION: Our results suggest that 3-isobutyl
      methylxanthine might function through a p53-dependent mechanism.

PMID- 16614703
TI  - Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal
      cancer cells.
AB  - AIM: Ganoderma lucidum is a commonly used Chinese herb and an important
      ingredient in traditional Chinese medicine herbal formulations for immune
      dysfunction related illnesses. The effects of this medicinal mushroom on human
      colorectal cancer cells have not yet been evaluated. In this study, we
      investigated the effects of Ganoderma lucidum extract using SW 480 human
      colorectal cancer cell line. MATERIALS AND METHODS: Two different fractions of
      Ganoderma lucidum extract, i.e., a fraction containing mainly polysaccharides
      (GLE-1), and a triterpenoid fraction without polysaccharides (GLE-2) were
      analyzed. Their antiproliferative activity was evaluated by cell proliferation
      assay and 3H-thymidine incorporation assay. Scavenging effects of DPPH radical
      were assessed using ESR-spectroscopy. RESULTS: Our data showed that both GLE-1
      and GLE-2 significantly inhibited the proliferation of SW 480 cells. The
      inhibitory effect of GLE-2 was much stronger than that of GLE-1. GLE-1 inhibited
      DNA synthesis in the cells and reduced the formation of DPPH radicals.
      CONCLUSION: Ganoderma lucidum extract inhibits proliferation of human colorectal
      cancer cells and possesses antioxidant properties.

PMID- 16614704
TI  - beta-lapachone induces growth inhibition and apoptosis in bladder cancer cells by
      modulation of Bcl-2 family and activation of caspases.
AB  - AIM: To study in vitro the molecular mechanism of apoptosis caused by beta
      lapachone, a quinone obtained from the bark of the lapacho tree (Tabebuia
      avellanedae). MATERIALS AND METHODS: The study was carried out on human bladder
      carcinoma T24 cell line. Determination of cell viability was done using trypan
      blue exclusion method, apoptosis quantitative estimation - by DAPI staining and
      agarose gel electrophoresis for DNA fragmentation. Flow cytometry analysis, RT
      PCR and Western blot analysis, colorimetric assay of caspase activity were
      applied as well. RESULTS: It was found that in micromolar range of concentrations
      beta-lapachone inhibited the viability of T24 cells by inducing apoptosis, which
      could be proved by formation of apoptotic bodies and DNA fragmentation. Treatment
      of T24 cells with beta-lapachone resulted in a down-regulation of Bcl-2
      expression and up-regulation of Bax expression. beta-lapachone-induced apoptosis
      was also associated with activation of caspase-3 and caspase-9, inhibition of IAP
      expression, and degradation of poly (ADP-ribose) polymerase, phospholipase C
      gamma1 and beta-catenin proteins. At the same time Fas and FasL levels were
      inhibited upon treatment with beta-lapachone in a concentration-dependent manner.
      CONCLUSION: beta-lapachone-induced apoptosis in T24 cells is mediated, at least
      in part, by the mitochondrial-signaling pathway.

PMID- 16614705
TI  - Osteopontin regulation by protein kinase B (Akt) in HepG2 cells.
AB  - AIM: The mechanism responsible for osteopontin regulation is not understood in
      HepG2 cells. The aim of this study was to investigate the relationship between
      protein kinase B (Akt), a key gene in PI3K signal transduction pathway, and
      osteopontin expression. METHODS: HepG2 cells were transfected with constitutively
      active Akt and dominant negative Akt using lipofectin. The Akt transfection was
      confirmed by Western blot analysis. Osteopontin expression was detected by both
      Northern blot and Western blot. RESULTS: Overexpression of exogenous Akt was
      detected in HepG2 cells by Western blot, indicating that HepG2 cells were
      successfully transfected with the Akt genes. In serum-free condition, the
      expression of osteopontin was either low or undetectable in HepG2 cells
      transfected with vector only, however, the expression increased after
      transfection of cells with constitutively active Akt. Osteopontin expression
      decreased when HepG2 cells were transfected with dominant negative Akt.
      CONCLUSION: Protein kinase B (Akt) gene regulated osteopontin expression in RNA
      level and protein level, suggesting that osteopontin synthesis can be blocked by
      inactivation of the Akt gene. This leads to a potential means of intervention for
      the inhibition of metastases in liver cancer.

PMID- 16614706
TI  - The association between CD99 and LMP-1 expression in nasopharyngeal carcinoma.
AB  - AIM: To characterize the roles of LMP-1 and CD99 in nasopharyngeal
      carcinogenesis, we undertook this pilot study of LMP-1 and CD99 expressions in
      nasopharyngeal cancer (NPC). MATERIALS AND METHOD: 40 NPC tissue samples were
      grouped according to the WHO classification. Immunohistochemical studies were
      performed using monoclonal antibodies against EBV latent membrane protein 1 (LMP
      1) and CD99 protein. In addition, CD99 expression was evaluated in 10 samples of
      non-neoplastic nasopharyngeal epithelium. RESULTS: LMP-1 was detected in 12 of
      the 40 (30.0%) cases and its expression was found to be confined to epithelial
      tumor cells. WHO type I NPC samples were completely negative for LMP-1, whereas
      WHO type III NPC samples showed highest expression. Interestingly, CD99 was
      expressed in all of the non-neoplastic nasopharyngeal epithelium samples along
      the cytoplasmic border. CD99 expression was noted in NPC tumor cells (5 of the 40
      cases, 12.5%) and in surrounding lymphoid stroma (23 of the 40 cases, 57.5%), but
      was not expressed in WHO type I NPC. In the 12 LMP-1 positive cases, 9 cases
      (75.0%) were CD99 negative, and 3 cases (25.5%) were CD99 positive. There was a
      statistical significance between LMP-1 and CD99 expression in lymphoid stroma.
      CONCLUSION: Our results suggest that the LMP-1 induced down-regulation of the
      CD99 pathway is important in nasopharyngeal carcinogenesis, and that the
      expression of CD99 in lymphoid stroma may regulate immune response to NPC.

PMID- 16614707
TI  - Expression profiling of cyclin B1 and D1 in cervical carcinoma.
AB  - AIM: Cyclins are a family of regulatory proteins that play a key role in
      controlling the cell cycle. Abnormalities of cell cycle regulators, including
      cyclins and cyclin dependent kinases, have been reported in various malignant
      tumors. This study was undertaken to quantitatively detect cyclin B1 and D1 in
      cervical cancer. METHODS: A quantitative real-time reverse transcription
      polymerase chain reaction and Western blot assay were used to analyze the
      expression of cyclin B1/D1 mRNA and proteins, respectively, in fresh invasive
      cervical cancer (n = 41) and normal cervical tissues (n = 10). RESULTS: There was
      significantly greater cyclin B1 expression in invasive cervical cancer than in
      normal cervical tissue (P = 0.019). However, cyclin D1 expression was not
      significantly different. A Western blot assay yielded similar results.
      CONCLUSION: Our results were consistent with the concept that up-regulation of
      cyclin B1 expression occurred in cervical cancer and an aberrant expression of
      cyclin B1 might play an important role in cervical carcinogenesis.

PMID- 16614708
TI  - Effects of radical oxygen species and NO: formation of intracellular hypoxia and
      activation of matrix metalloproteinases in tumor tissues.
AB  - AIM: To establish the association between the radical oxygen species (ROS) and NO
      levels in the tumor cells mitochondria, between cell hypoxia development and
      activation of matrix metalloproteinases-2 and -9. MATERIALS AND METHODS: Electron
      paramagnetic resonance (EPR) at room temperature and at the temperature of liquid
      nitrogen (77 degrees K), spin traps technology, enzymography in polyacrylamide
      gel were applied. RESULTS: Redox-centers in the respiration cascade of
      mitochondria have been revealed, multiple oxidative damage of which in breast and
      liver cancer tissues of experimental animals as well as in tumor tissue from
      patients with gastric cancer promote the development of cell hypoxia. Involvement
      of ROS and NO in activation of latent forms of matrix metalloproteinases in
      gastric tumor tissues has been shown. CONCLUSION: We hypothesize that superoxide
      radical-anions participate in development of cell hypoxia in tumors and
      surrounding normal tissues inducing activation of latent forms of matrix
      metalloproteinases.

PMID- 16614709
TI  - Circadian rhythms of cytotoxic activity in peripheral blood mononuclear cells of
      patients with malignant melanoma.
AB  - AIM: To study circadian rhythms (CR) of cytotoxic activity in peripheral blood
      mononuclear cells of patients with malignant melanoma were compared with those in
      healthy men. METHODS: The NK-cell and phagocyte cytotoxic activity in five
      patients with malignant melanoma stage I or II and 12 healthy donors has been
      assessed by radioimmune assay and NBT-test. RESULTS: The circadian rhythmicity in
      NK-cells and phagocyte activity in all cancer patients under study has been
      disrupted. The extent of such disruption tended to increase in patients with more
      advanced cancer. The most typical alterations were discoordination between the
      cytotoxicity rhythms of NK-cells and phagocytes (synchronized in healthy persons)
      and alterations in basic rhythm parameters: phase shifts and amplitude damping.
      CONCLUSION: In melanoma patients the significant alteration of CR in NK-cells and
      phagocytes cytotoxic activity was revealed. In spite of individual variations,
      the degree of the rhythm disruption basically depended on a disease stage. The
      alteration of CR phase and amplitude and discoordination between the rhythms of
      NK-cells and phagocyte were registered in all cases studied.

PMID- 16614710
TI  - Patterns of hematological malignancies in Chernobyl clean-up workers (1996-2005).
AB  - AIM: The question as to whether the incidence of leukemias and malignant
      lymphomas among the Chernobyl clean-up workers increased in 20 years after the
      catastrophe is still a point of much controversy. Precise diagnosis of the main
      forms of hematopoietic malignancies according to FAB classification and new WHO
      classification and comparison of these data with that in the general population
      will be helpful in estimating the relative contribution of the radiation factor
      to the overall incidence of such pathologies. PATIENTS AND METHODS: The data on
      218 consecutive cases of malignant diseases of hematopoietic and lymphoid tissues
      in Chernobyl clean-up workers diagnosed in 1996-2005 are given in comparison with
      the data of 2697 consecutive patients of general population of the same age
      group. The morphology and cytochemistry of bone marrow and peripheral blood cells
      were studied. Immunocytochemical techniques (APAAP, LSAB-AP) and the broad panel
      of monoclonal antibodies to lineage specific and differentiation antigens of
      leukocytes were employed for immunophenotyping leukemic cells. RESULTS: Various
      types of oncohematological diseases developing 10-20 years after Chernobyl
      accident were registered in a group of clean-up workers under study including
      myelodysplastic syndromes (MDS), acute leukemias (ALL and AML), chronic
      myelogenous leukemia (CML) and other chronic myeloproliferative diseases, chronic
      lymphocytic leukemia (B-CLL) and other chronic lymphoproliferative diseases of B
      and T cell origin. MDS percentage among patients of clean-up workers group tended
      to exceed MDS percentage in the group of patients representing the general
      population examined at the same period (4.58 vs. 3.70%). Among 34 AML cases,
      leukemia was preceded by MDS in seven patients. The relative contribution of CML
      to the total number of clean-up workers with leukemia was higher than the
      corresponding percentage value in general population examined at the same period
      (9.17 vs. 6.59%). B-CLL was a predominant form of hematopoietic malignancies in
      clean-up workers under study (25.68%). Nevertheless, B-CLL percentage in patients
      of clean-up workers group did not differ significantly from that in the patients
      of general population. The multiple myeloma percentage (7.79%) in the group of
      patients belonging to clean-up workers in our study turned out to be twice as
      much as in the patients of general population (4.0%). CONCLUSION: The verified
      diagnosis of tumors of hematopoietic and lymphoid tissue according to modern
      classification (EGIL, WHO) could be the prerequisite for further molecular
      genetic and analytical epidemiology study of leukemias that may be related to
      Chernobyl NPP accident consequences.

PMID- 16614711
TI  - Genotoxic factors associated with the development of receptor-negative breast
      cancer: potential role of the phenomenon of switching of estrogen effects.
AB  - AIM: About 30-40% of breast cancers lack steroid receptors (ER and/or PR) at
      diagnosis that worsen prognosis and limit the usage of hormone therapy. The aim
      of this paper has been to study the role of DNA-damaging factors as the potential
      modifiers of the receptor-negative tumors incidence. MATERIALS AND METHODS: The
      investigation consisted of two principal parts. In one of them ER and PR content
      was measured in breast cancer samples from 2284 primary patients (350 of them -
      current or previous smokers). In separately studied subgroup of 1010 patients 95
      suffered with diabetes mellitus type II. RESULTS: As it was shown, smokers and
      diabetics carry more frequently (p = or < 0.05) tumors with phenotypes ER+PR- and
      PR- only in the group of women with conserved menstrual cycle that is in case of
      relatively higher estrogenic stimulation. In another part of the investigation
      immunohistochemical study of DNA damage marker - 8-hydroxy-2-deoxyguanosine (8-OH
      dG) in 16 R(-) and 18 R(+) breast cancer specimens demonstrated more frequent
      positive staining in the former group of samples (p = 0.05). Besides, as it was
      revealed in breast cancer cell line MCF-7 the combination of estradiol with aryl
      hydrocarbonic receptors agonist beta-naphtoflavone induced pronounced genotoxic
      damage (by 8-OH-dG content) in association with the loss of ER. CONCLUSION: Thus,
      pro-genotoxic status (smoking, diabetes) and direct signs of genotoxic injury, in
      accordance with regularities of the phenomenon of switching of estrogen effects
      can be reckoned among the factors promoting the development of receptor-negative
      breast cancer.

PMID- 16614712
TI  - The efficacy of the thyroid peroxidase marker for distinguishing follicular
      thyroid carcinoma from follicular adenoma.
AB  - AIM: Expression of thyroid peroxidase (TPO) in the thyroid gland tissue is well
      known as a sensitive marker of the thyroid malignancy. We have evaluated
      immunohistochemical assay of TPO for distinguishing follicular thyroid carcinoma
      from follicular adenoma. MATERIALS AND METHODS: Sections of formalin-fixed
      tissues obtained from 92 patients with thyroid tumors (52 follicular carcinomas
      and 40 follicular adenomas including the Hurthle cell type) were analyzed using a
      monoclonal antibody (TPO mAb 47) and the avidin-biotin peroxidase complex
      immunohistochemical technique. Lesions with staining of more than 80% of the
      follicular cells/specimen were considered benign, while less than 80% were
      considered malignant. RESULTS: TPO immunostaining correlated with the
      histopathological diagnosis in 24/40 cases of follicular adenomas and 41/52 cases
      of follicular carcinomas, giving a specificity of 60% and a sensitivity of 79%.
      CONCLUSION: These results suggest that immunohistochemical assay of TPO
      expression has limited value for the differential diagnosis of follicular thyroid
      carcinoma from thyroid follicular adenoma.

PMID- 16614713
TI  - First treatment activity and outcome of radioiodine therapy in thyroid cancer
      patients with metastases in lymph nodes: mathematical correlation and clinical
      implications.
AB  - AIM: The aim of the work was to estimate the strength of influence of the first
      (131)I activity on the outcome of the first course of radioiodine treatment as
      compared with other variables such as remnants volume, size and number of
      metastases in lymph nodes. PATIENTS AND METHODS: 68 adult patients with
      differentiated thyroid cancer have been treated with radioiodine after
      thyroidectomy. All patients had metastatic lesions in lymph nodes accumulating
      (131)I. Activities administered amounted from 1000 to 6000 MBq. From 1 to 4
      courses of radioiodine therapy were necessary for total ablation of metastases
      and remnants. Logistic function has been used to describe the probability of the
      total ablation of metastases and thyroid remnants after the first course.
      RESULTS: It was shown that the value of the first activity has the decisive
      influence on the treatment outcome. In patients included into analysis the
      outcome of the first course actually does not depend on level of radioiodine
      accumulation in pathological lymph nodes and effective half-time of (131)I
      excretion in remnants. CONCLUSION: As a result, in the case of metastatic lesions
      in lymph nodes accumulating radioiodine the first activity should not be less
      then 5000 MBq with the aim of minimizing the number of courses. Outcome of the
      treatment only slightly depends on such factors as histology, the number and the
      size of metastases in lymph nodes.

PMID- 16614714
TI  - The effect of hypoxia on photocytotoxicity of TICS tricarbocyanine dye in vitro.
AB  - AIM: To evaluate the effect of cell oxygenation on photocytotoxicity of a novel
      tricarbocyanine indolenine dye covalently bound to glucose (TICS). METHODS: HeLa
      cells were incubated with 5 microM TICS, 2 h later irradiated by laser at 740 nm
      with a light dose of 10 J/cm(2), delivered at a power density of 10, 20, 25 or 30
      mW/cm(2), in air or in argon atmosphere, and then scored for viability. RESULTS:
      The photocytotoxicity of TICS increased dramatically as the power density was
      reduced. Under hypoxia TICS-photosensitized cell death was determined but its
      value was lowered, compared to photoirradiation in the air. CONCLUSION:
      Photosensitizing effect of TICS is only partially dependent on the oxygenation of
      tumor cells.

PMID- 16614715
TI  - The clinical significance of soluble E-cadherin in nonsmall cell lung cancer.
AB  - AIM: Aberrant expression of the epithelial transmembrane adhesion molecule E
      cadherin (E-cad) has been associated with many human malignancies. In the present
      study the clinical significance of serum levels of soluble E-cadherin (sE-cad) in
      newly diagnosed patients with non small cell lung cancer (NSCLC) was
      investigated. MATERIAL AND METHODS: An enzyme linked immunospecific assay (ELISA)
      to determine the circulating levels of sE-cad in 20 newly diagnosed patients with
      NSCLC as well as in 29 healthy volunteers (control group) was used. RESULTS:
      NSCLC patients exerted increased circulating levels of sE-cad compared with
      individuals of the control group (p < 0.001). An association was also detected
      between serum sE-cad levels and the development of distant metastases. On the
      contrary, no statistically significant correlation could be established with
      histological type, gender and smoking habits. Patients with increased sE-cad
      levels at diagnosis had worser outcome, although multivariate analysis failed to
      demonstrate that sE-cad levels represent an independent prognostic factor of
      survival. CONCLUSION: Our data suggest that E-cad plays a role in the
      pathogenesis of NSCLC. sE-cad levels may be further studied as a potential
      prognostic biomarker.

PMID- 16614716
TI  - Protective effect of antioxidant enzymes against drug cytotoxicity in MCF-7
      cells.
AB  - AIM: To evaluate protective effect of antioxidant enzymes against epirubicin-HCI
      (EPI) cytotoxicity in vitro. MATERIALS AND METHODS: Viability of MCF-7 cells
      treated with EPI was measured using the MTT test. Glutathione (GSH), protein
      content and enzymatic activity were measured spectrophotometrically. NADPH -
      dependent cytochrome P-450 reductase (NADPH-CYP-450) and glutathione S
      transferase pi (GST-pi) expression in MCF-7 cells were determined by Western blot
      analysis. RESULTS: The IC50 values of EPI in MCF-7 cells were 1.0, 0.7 and 0.5
      ng/ml respectively for 24, 48 and 72 h applications. Simultaneously enzymatic
      activity of glutathione S-transferase, glutathione peroxidase, GSH and expression
      of GST-pi, NADPH-CYP-450 reductase were increased in EPI (1 ng/ml) - treated
      cells at the end of the 24 h incubation. Addition of superoxide dismutase,
      catalase and GSH decreased cytotoxicity of EPI. CONCLUSION: We hypothesized that
      the production of reactive oxygen species and hydrogen peroxide as result of EPI
      treatment can cause cytotoxicity in MCF-7 cells and antioxidant enzymes protect
      the cells against this process.

PMID- 16614717
TI  - Natural antibodies to endotoxin in experimental and clinical oncology.
AB  - The studies on natural endotoxin immunity, carried out at Preventive Immunology
      Laboratory of Institute of Oncology of Vilnius University have shown that the
      natural immune functions of both immunostimulated and immunosuppressed organisms
      are closely related to IgM class natural antibodies (IgMNA) to the
      enterobacterial common antigen (ECA) from membranes of intestinal microorganisms,
      i.e. endogenous or spontaneous antibodies to endotoxin. With aging, when cellular
      immunity functions deteriorate, the level of these NA to endotoxin (NAE) in blood
      serum increases. The population level of NAE is enhanced by carcinogens and
      chemotherapeutic drugs in dependence from their doses and downregulated by
      tobacco smoking, alcohol consumption, exposure to environmental pollution,
      professional exposure to harmful agents, and chronic diseases. IgMNAE reflects
      enhancement of the natural immune functions of the organism on the background of
      the suppressed functions of classic cellular immunity and suits well to our new
      conception of elucidating the natural compensatory responses of immune
      homeostasis related to immune response to endotoxin.

PMID- 16614718
TI  - Symptomatic hyponatremia with hypoxia is a medical emergency.
AB  - Patients presenting with the combined finding of severe symptomatic hyponatremia
      and hypoxia have such high mortality rates that they should be admitted to an
      intensive care unit and intubated sooner rather than later. Without delay, these
      patients need rapid correction of their serum sodium by 8-10 mequiv. per liter
      and an increase in their partial pressure of arterial oxygen to values above 70
      mm Hg.

PMID- 16614719
TI  - Cholesterol crystal embolism: diagnosis and treatment.
AB  - Cholesterol crystal embolization (CCE) is a dreaded complication of radiology,
      vascular surgery, and/or anticoagulation in patients with atherosclerosis and
      ulcerated aortic plaques. It also represents a cause of early graft failure and
      of poor results of renal artery surgery. Crystals lodge in small caliber renal
      arteries, where they induce early, transitory thrombosis followed by delayed,
      definitive obstruction by endarteritis, accompanied by evidence of inflammation
      and eosinophilia. Massive CCE leads to early oligoanuria. In subacute forms,
      renal insufficiency is often delayed by weeks or months following the triggering
      event. A third, chronic subset of CCE is easily mistaken for atherosclerotic
      renal ischemia and/or nephrosclerosis. The kidney is rarely the sole organ
      involved in acute/subacute forms, in which the central nervous system, the
      coronary arteries, the spinal cord, and the mesenteric and pancreatic blood
      supply compromise represent the main causes of death. Cutaneous, retinal, and
      muscle involvement allow diagnosis by inspection or scarcely invasive biopsies in
      about 80% of cases, whereas renal biopsy as the only diagnostic procedure is
      required in 20% of cases. Prevention is based on avoidance of endovascular
      radiology maneuvers, vascular surgery, and excess anticoagulation in
      atherosclerotic patients. Treatment of acute/subacute forms of renal
      insufficiency consisting of stopping anticoagulation and forbidding any new
      radiologic and/or vascular surgery procedure; treating hypertension with
      angiotensin 2 antagonists and vasodilators, strict volemic control by loop
      diuretics and ultrafiltration, along with parenteral nutrition and prednisone,
      has been credited with improved outcome. Iloprost may obtain favorable results.
      Statins definitely ameliorate the renal and patient's prognosis.

PMID- 16614720
TI  - Randall's plaque: pathogenesis and role in calcium oxalate nephrolithiasis.
AB  - The purpose of these studies was to test the hypothesis that Randall's plaque
      develops in unique anatomical sites of the kidney and their formation is
      conditioned by specific stone-forming pathophysiologies. We performed
      intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate
      (CaOx), intestinal bypass for obesity, brushite (BR) and cystine stone formers
      (SF) during percutaneous nephrolithotomy. Tissues were examined by infrared
      analysis and light and electron microscopy. Our analysis revealed a distinct
      pattern of mineral deposition and papillary pathology for each type of SF. CaOx
      SF had interstitial apatite crystals beginning at thin loops of Henle. These
      deposits termed Randall's plaque are thought to serve as sites for stone
      attachment. No tubular injury was noted. Intestinal bypass patients possessed
      intraluminal apatite deposits in inner medullary collecting ducts (IMCD) with
      associated cell injury. BR SF showed the most severe form of cortical and
      medullary changes with sites of Randall's plaque, and yellowish intraluminal
      deposits of apatite in IMCD. Cystine SF had plugging of ducts of Bellini with
      cystine crystals and apatite deposits in IMCD and loops of Henle. Intratubular
      sites of crystalline deposits were always associated to adjacent regions of
      interstitial fibrosis. The metabolic, anatomic, and surgical pathologic findings
      in four distinct groups of SF clearly show that 'the histology of the renal
      papilla from a stone former, is particular to the clinical setting'. We believe
      our approach to studying stone disease will provide insights into the
      pathogenesis of stone formation for each type of SF that will lead to improved
      clinical treatment.

PMID- 16614721
TI  - Hyponatremia with hypoxia: effects on brain adaptation, perfusion, and histology
      in rodents.
AB  - Hypoxia appears to be a prominent component of brain damage among patients with
      hyponatremic encephalopathy. Effects of hypoxia on brain in the presence of
      hyponatremia are not known. In order to evaluate the contributions of hypoxia to
      brain damage, three separate experiments were conducted in three groups of
      rodents. Experiment I evaluated the effects of hypoxia and acute (< 4 h)
      hyponatremia (plasma Na < 120 mmol/l) on brain adaptation in rabbits. Experiment
      II evaluated the effects of hypoxia and chronic (4 days) hyponatremia on cerebral
      perfusion in rats. Experiment III evaluated the effects of hypoxia and chronic
      hyponatremia on brain histology in rats. In experiment I, rabbits with acute
      hyponatremia demonstrated brain adaptation with significant falls in brain Na
      content (by 14.2%, P < 0.01) and osmolality (by 8.3%, P < 0.01), and a rise in
      brain water (by 10.6%, P < 0.05). Rabbits with combined hypoxia and hyponatremia
      failed to demonstrate brain adaptation. In experiment II, rats with chronic
      hyponatremia plus hypoxia had a decrease in cerebral perfusion index by more than
      50% (P < 0.01). In experiment III, 23% of hypoxic rats had brain lesions, which
      were in the cerebellum, thalamus, reticular formation, and basal ganglia.
      Hyponatremia without hypoxia resulted in no brain lesions. Hypoxia in
      normonatremic animals results in cerebral edema and histopathologic lesions
      similar to those found in rats whose plasma Na was overcorrected. Hypoxia in
      hyponatremic animals aggravates cerebral edema, impairs brain adaptation, and
      decreases cerebral perfusion.

PMID- 16614722
TI  - Novel keratin 14 mutations in patients with severe recessive epidermolysis
      bullosa simplex.

PMID- 16614723
TI  - PI3-kinase subunits are infrequent somatic targets in melanoma.

PMID- 16614724
TI  - Seasonal and latitudinal impact of polymorphic light eruption on quality of life.

PMID- 16614725
TI  - The A148T variant of the CDKN2A gene is not associated with melanoma risk in the
      French and Italian populations.

PMID- 16614726
TI  - Carbazole is a naturally occurring inhibitor of angiogenesis and inflammation
      isolated from antipsoriatic coal tar.
AB  - Coal tar is one of the oldest and an effective treatment for psoriasis. Coal tar
      has been directly applied to the skin, or used in combination with UV light as
      part of the Goeckerman treatment. The use of coal tar has caused long-term
      remissions in psoriasis, but has fallen out of favor because the treatment
      requires hospitalization and coal tar is poorly acceptable aesthetically to
      patients. Thus, determining the active antipsoriatic component of coal tar is of
      considerable therapeutic interest. We fractionated coal tar into its components,
      and tested them using the SVR angiogenesis inhibitor assay. Treatment of SVR
      endothelial cells with coal tar fractions resulted in the isolation of a single
      fraction with antiangiogenic activity. The active antiangiogenic compound in coal
      tar is carbazole. In addition to antiangiogenic activity, carbazole inhibited the
      production of inflammatory IL-15 by human mononuclear cells. IL-15 is elevated in
      psoriasis and is thought to contribute to psoriatic inflammation. Carbazole
      treatment also reduced activity of inducible nitric oxide synthase (iNOS), which
      is proinflammatory and elevated in psoriasis. The effect of carbazole on upstream
      pathways in human psoriasis was determined, and carbazole was shown to inhibit
      signal transducer and activator of transcription (stat)3-mediated transcription,
      which has been shown to be relevant in human psoriasis. IL-15, iNOS, and stat3
      activation require the activation of the small GTPase rac for optimal activity.
      Carbazole was found to inhibit rac activation as a mechanism for its inhibition
      of downstream inflammatory and angiogenic pathways. Given its antiangiogenic and
      anti-inflammatory activities, carbazole is likely a major component of the
      antipsoriatic activity of coal tar. Carbazole and derivatives may be useful in
      the therapy of human psoriasis.

PMID- 16614727
TI  - 40 nm, but not 750 or 1,500 nm, nanoparticles enter epidermal CD1a+ cells after
      transcutaneous application on human skin.
AB  - Although conventional vaccines have generated major successes in the control of
      infectious diseases, several obstacles remain in their development against
      chronic diseases (HIV, tuberculosis), against which no current candidate vaccines
      yet ensure protection. The transcutaneous route of vaccine administration appears
      to be a promising approach of targeting vaccines toward antigen-presenting cells
      (APCs) and thus improving immune responses. We investigated the suitability of
      nanoparticles in this approach. We found a high density of Langerhans cells (LCs)
      around hair follicles that, when sorted, readily internalized all size particles.
      However, flow cytometry after transcutaneous application of 40, 750, or 1,500 nm
      nanoparticles on human skin samples revealed that only 40 nm particles entered
      epidermal LC. Fluorescence and laser scan microscopies, which were carried out to
      identify the penetration pathway of transcutaneously applied nanoparticles,
      revealed that only 40 nm particles deeply penetrate into vellus hair openings and
      through the follicular epithelium. We conclude that 40 nm nanoparticles, but not
      750 or 1,500 nm nanoparticles, may be efficiently used to transcutaneously
      deliver vaccine compounds via the hair follicle into cutaneous APCs.

PMID- 16614728
TI  - Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-Cell
      lymphomas suggesting impaired cell cycle control in disease pathogenesis.
AB  - Upregulation of cyclin D1/B-cell leukemia/lymphoma 1 (CCND1/BCL1) is present in
      most mantle cell lymphomas with the t(11;14)(q13;q32) translocation. However,
      little is known about the abnormalities of CCND1 and its regulator RB1 in primary
      cutaneous T-cell lymphomas (CTCL). We analyzed CCND and RB status in CTCL using
      fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and
      Affymetrix expression microarray. FISH revealed loss of CCND1/BCL1 in five of
      nine Sezary syndrome (SS) cases but gain in two cases, and RB1 loss in four of
      seven SS cases. IHC showed absent CCND1/BCL1 expression in 18 of 30 SS, 10 of 23
      mycosis fungoides (MF), and three of 10 primary cutaneous CD30+ anaplastic large
      cell lymphoma (C-ALCL). Increased CCND1/BCL1 expression was seen in nine MF,
      seven C-ALCL, and six SS cases. Absent RB1 expression was detected in 8 of 12 MF
      and 7 of 9 SS cases, and raised RB1 expression in 7 of 8 C-ALCL. Affymetrix
      revealed increased gene expression of CCND2 in four of eight CTCL cases, CCND3 in
      three cases, and CDKN2C in two cases with a normal expression of CCND1 and RB1.
      These findings suggest heterogeneous abnormalities of CCND and RB in CTCL, in
      which dysregulated CCND and RB1 may lead to impaired cell cycle control.

PMID- 16614730
TI  - Hypoxic pulmonary hypertension (HPH) and iptakalim, a novel ATP-sensitive
      potassium channel opener targeting smaller arteries in hypertension.
AB  - Hypoxic pulmonary hypertension (HPH) is a serious and potentially devastating
      chronic disorder of the pulmonary circulation. Attempts to use drugs in the
      therapy of hypoxic pulmonary hypertension indicated the importance of prevention
      or reduction of vasoconstriction as well as of the reversal of remodeling within
      the cardiovascular system. Iptakalim (2,3-dimethyl-N-(1-methylethyl)-2
      butylamine), a novel ATP-sensitive potassium channel opener, has the desired
      effects on hypoxic pulmonary arteries. Iptakalim decreases the elevated mean
      pressure in pulmonary arteries, and attenuates remodeling in the right ventricle,
      pulmonary arteries and airways. Moreover, iptakalim has selective
      antihypertensive effects: it significantly lowers arterial pressure in
      hypertensive animals, but has little if any effect in normotensive animals. In
      HPH iptakalim has selective effects on smaller arteries. Long-term iptakalim
      therapy decreases expression of sulfonylurea receptor 2 and of mRNA of inwardly
      rectifying potassium channel in smaller arteries of spontaneously hypertensive
      rats. Iptakalim inhibits the effects of endothelin-1, reduces the intracellular
      calcium concentration and inhibits the cell cycle in smooth muscle cells of
      pulmonary arteries. There is no evidence for the development of tolerance to the
      long-lasting antihypertensive action of iptakalim. At therapeutic doses iptakalim
      has no effects on the central nervous, respiratory, digestive, or endocrine
      systems. It has a broad therapeutic range, so that it can be safely used in the
      therapy of HPH.

PMID- 16614729
TI  - Statins, nitric oxide and neovascularization.
AB  - Several landmark clinical trials suggest that 3-hydroxyl-3-methylglutaryl
      coenzyme A reductase inhibitors (statins) have additional cardiovascular
      protective activity that may function independently of their ability to lower
      serum cholesterol. The cardiovascular protective effects of statins are partly
      caused by the activation of postnatal neovascularization. At therapeutic doses,
      statins promote proliferation, migration and survival of endothelial cells,
      induce mobilization and differentiation of bone marrow-derived endothelial
      progenitor cells by stimulating the serine/threonine protein kinase Akt (also
      known as protein kinase B) and nitric oxide (NO) signal pathway. However, at
      excessive doses, statins may decrease protein isoprenylation as well as inhibit
      endothelial cell growth and migration. NO is an important signaling molecule that
      regulates a wide range of physiological and pathological processes in different
      tissues. There is substantial evidence that effective neovascularization requires
      endothelium-derived NO. Statins have pleiotropic effects on the expression and
      activity of endothelial nitric oxide synthase (eNOS) and lead to improved NO
      bioavailability. NO plays an important role in the effects of statins on
      neovascularization. In this review, we focus on the effects of statins on
      neovascularization and highlight specific novel targets, such as endothelial
      progenitor cells and NO.

PMID- 16614731
TI  - CGS 35601, a triple inhibitor of angiotensin converting enzyme, neutral
      endopeptidase and endothelin converting enzyme.
AB  - CGS 35601 (L-tryptophan, N-[[1-[[(2S)-2-mercapto-4-methyl-1-oxopentyl]amino]
      cyclopentyl]carbonyl]) is one of a few single molecules capable of inhibiting the
      activities of angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP)
      and endothelin converting enzyme (ECE) simultaneously, with IC(50) values of 22,
      2, and 55 nM, respectively. Through the inhibition of ACE and ECE, it blocks the
      conversion of angiotensin I (AI) and big endothelin-1 (big ET-1) into the two
      most potent peptidic vasoconstrictors, angiotensin II (AII) and ET-1,
      respectively. By inhibiting NEP, CGS 35601 also prevents the degradation of
      peptidic vasodilators such as bradykinin (BK), natriuretic peptides (NPs) and
      adrenomedullin (ADM) and, hence, modulates the secondary release of other
      vasoactive mediators such as nitric oxide (NO) and prostaglandins. In chronic (30
      days) experiments, CGS 35601 is well tolerated with a very good safety profile in
      healthy normotensive, hypertensive and type 2 diabetic rats. The antihypertensive
      efficacy of CGS 35601 was demonstrated in chronically instrumented, unrestrained
      and conscious rat models of hypertension (SHR and DSS) and type 2 diabetes (ZDF
      fatty). It lowered blood pressure effectively as well as modulated plasma
      concentrations of a number of circulating vasoactive peptidic mediators that are
      keys to the regulation of the vascular tone. These data suggest that CGS 35601, a
      triple vasopeptidase inhibitor (VPI), may represent a novel class of
      antihypertensive drugs and may have the potential to reduce morbidity and
      mortality from cardiovascular disorders, diabetes and subsequent renal
      complications. Similar in vivo ACE, NEP, and ECE inhibitory activities were also
      observed with the orally active prodrug, CGS 37808 (L-tryptophan, N-[[1-[[(2S)-2
      (acetylthio)-4-methyl-1-oxopentyl]amino]cyclopentyl]-carbonyl]-, methyl ester.

PMID- 16614732
TI  - Ximelagatran, the new oral anticoagulant: would warfarin survive the challenge?
AB  - The last decade witnessed major advances in the prevention and treatment of
      venous as well as of arterial thrombosis. Limitations of existing anticoagulants
      led to the development of novel therapeutic approaches. Ximelagatran is a new
      direct thrombin inhibitor (DTI) that is given orally, without the need for close
      monitoring. This compound was tried in the treatment of active venous
      thromboembolism, and the results were encouraging. Randomized trials suggest that
      ximelagatran is not inferior to warfarin in the prevention of stroke in patients
      with nonvalvular atrial fibrillation. Multiple controlled, prospective trials
      compared ximelagatran with low molecular weight heparin or warfarin in prevention
      of venous thromboembolism in patients undergoing major orthopedic procedures. The
      results of these clinical trials are reviewed in this article. Because of certain
      safety concerns (increased liver enzymes, potential hepatonecrosis, and increased
      coronary events) ximelagatran has not yet been approved by the FDA. Additional
      studies may be required to address these concerns. Ximelagatran has been
      approved, however, by the European regulatory authorities for short-term
      thromboprophylaxis. The success of ximelagatran or other oral antithrombin agents
      would provide significant proof of the concept for the long-term use of oral
      antithrombins in the prevention and treatment of both arterial and venous
      thrombosis.

PMID- 16614733
TI  - Bivalirudin: pharmacology and clinical applications.
AB  - Bivalirudin (Hirulog, Angiomax) is a specific, reversible and direct thrombin
      inhibitor with a predictable anticoagulant effect. It is cleared by both
      proteolytic cleavage and renal mechanisms, predominantly glomerular filtration.
      Bivalirudin inhibits both circulating thrombin and fibrin bound thrombin directly
      by binding to thrombin catalytic site and anion-binding exosite I in a
      concentration-dependent manner. Bivalirudin prolongs activated partial
      thromboplastin time, prothrombin time, thrombin time and activated clotting time
      (ACT). ACT levels with bivalirudin do not correlate with its clinical efficacy.
      Bivalirudin with a provisional GpIIb/IIIa inhibitor is indicated in elective
      contemporary percutaneous coronary intervention (PCI). In respect to combined
      ischemic and hemorrhagic endpoints of death, myocardial infarction, unplanned
      urgent revascularization and major bleeding during PCI (including subgroups of
      patients with renal impairment and diabetes) bivalirudin is not inferior to
      unfractioned heparin and planned GpIIb/IIIa inhibitors. In addition, bivalirudin
      has been consistently shown to have significantly less in-hospital major bleeding
      than heparin alone or heparin in combination with a GpIIb/IIIa inhibitor.
      Bivalirudin appears to be also safe and effective during PCI in patients with
      heparin-induced thrombocytopenia. Finally, data from PCI studies support the
      safety and efficacy of bivalirudin, although its direct randomized comparison
      with unfractionated heparin is lacking.

PMID- 16614734
TI  - ATC0175: an orally active melanin-concentrating hormone receptor 1 antagonist for
      the potential treatment of depression and anxiety.
AB  - Melanin-concentrating hormone (MCH) has been implicated in a variety of
      physiological events. Recent studies clearly suggest that MCH plays an important
      role in the regulation of stress and emotion. To date, two receptor subtypes of
      MCH (MCH1R and MCH2R) have been identified. MCH1R has been suggested to mediate
      most of the physiological functions of MCH. Recently, we synthesized an orally
      active, nonpeptidic antagonist of MCH1R, N-(cis-4-{[4-(dimethylamino)quinazolin-2
      yl]amino}cyclohexyl)-3,4-difluorobenzamide hydrochloride (ATC0175). This compound
      is a potent antagonist with a high affinity for MCH1R and additional affinities
      for 5-HT1A and 5-HT2B receptors. The receptor binding and the functional assay
      (MCH-induced increase in [Ca2+]i) indicated that ATC0175 is a noncompetitive
      antagonist at MCH1Rs. ATC0175 exhibited anxiolytic effects in numerous animal
      models of anxiety including the elevated plus-maze test, social interaction test,
      stress-induced hyperthermia and maternal separation-induced vocalization. Like
      with other stress-related peptide receptor antagonists, such as antagonists of
      corticotropin-releasing factor or vasopressin V1b receptor antagonists,
      anxiolytic effects of ATC0175 were more pronounced in models containing a stress
      component. ATC0175 also exhibited antidepressant effects in the forced swimming
      test. ATC0175 increased swimming performance without altering climbing behavior,
      as observed with selective serotonin reuptake inhibitors. ATC0175 has adequate
      ADME profile (reasonable oral bioavailability and brain penetration) and potent
      oral activity in animal models. In contrast, ATC0175 did not affect spontaneous
      locomotor activity, hexobarbital-induced sleeping time and did not impair rotarod
      performance. Thus, ATC0175 may be devoid of unwanted central nervous system side
      effects, which are sometimes observed with current medications. In addition,
      ATC0175 was well tolerated in rat repeated toxicity study, and had no genotoxic
      liability. Therefore, ATC0175 has the potential to be effective in the treatment
      of patients with depression and/or anxiety disorders.

PMID- 16614735
TI  - NAP: research and development of a peptide derived from activity-dependent
      neuroprotective protein (ADNP).
AB  - Activity-dependent neuroprotective protein (ADNP) is essential for brain
      formation. Peptide activity scanning identified NAP (NAPVSIPQ) as a small active
      fragment of ADNP that provides neuroprotection at very low concentrations. In
      cell culture, NAP has demonstrated protection against toxicity associated with
      the beta-amyloid peptide, N-methyl-D-aspartate, electrical blockade, the envelope
      protein of the AIDS virus, dopamine, H2O2, nutrient starvation and zinc overload.
      NAP has also provided neuroprotection in animal models of apolipoprotein E
      deficiency, cholinergic toxicity, closed head injury, stroke, middle aged anxiety
      and cognitive dysfunction. NAP binds to tubulin and facilitates microtubule
      assembly leading to enhanced cellular survival that is associated with
      fundamental cytoskeletal elements. A liquid-chromatography, mass spectrometry
      assay demonstrated that NAP reaches the brain after either intravenous or
      intranasal administration. In a battery of toxicological tests including repeated
      dose toxicity in rats and dogs, cardiopulmonary tests in dogs, and functional
      behavioral assays in rats, no adverse side effects were observed with NAP
      concentrations that were approximately 500-fold higher than the biologically
      active dose. A Phase Ia clinical trial in the US assessed the tolerability and
      pharmacokinetics of intranasal administration of NAP in sequential ascending
      doses. The results supported the safety and tolerability of a single dose of NAP
      administered at up to 15 mg intranasally. Furthermore, dosing was recently
      completed for a second Phase I clinical trial in healthy adults and elderly
      volunteers with an intravenous formulation of NAP. NAP is poised for further
      clinical development targeting several indications, including Alzheimer's
      disease.

PMID- 16614736
TI  - TAT-GDNF in neurodegeneration and ischemic stroke.
AB  - The delivery of proteins across the blood-brain barrier is severely limited by
      their size and biochemical properties. Numerous peptides have been characterized
      in recent years that prevent neuronal death in vitro, but cannot be used
      therapeutically, since they do not cross cell membrane barriers. It has been
      shown in the 1990s that the HIV TAT protein is able to cross cell membranes even
      when coupled with larger peptides. It appears, therefore, that TAT fusion
      proteins may enter the brain, even when used systemically. Indeed, the systemic
      delivery of a TAT protein linked with glial-derived neurotrophic factor (GDNF)
      successfully transduced central nervous system (CNS) neurons in mice. When
      administered after optic nerve transection and focal cerebral ischemia, TAT-GDNF
      protected retinal ganglion cells and brain neurons from cell death, elevated
      tissue Bcl-XL levels and attenuated the activity of the executioner caspase-3.
      These findings demonstrate the in vivo efficacy of fusion proteins in clinically
      relevant disease models, raising hopes that neuroprotection may become eventually
      feasible in human patients.

PMID- 16614738
TI  - Guest editor's editorial: Advances in managing hepatitis C virus (HCV) infection
      (A special issue).

PMID- 16614737
TI  - A review of the neuroprotective properties of the 5-HT1A receptor agonist
      repinotan HCl (BAYx3702) in ischemic stroke.
AB  - Repinotan HCl (repinotan, BAYx3702), a highly selective 5-HT1A receptor agonist
      with a good record of safety was found to have pronounced neuroprotective effects
      in experimental models that mimic various aspects of brain injury. Repinotan
      caused strong, dose-dependent infarct reductions in permanent middle cerebral
      artery occlusion, transient middle cerebral artery occlusion, and traumatic brain
      injury paradigms. The specific 5-HT1A receptor antagonist WAY 100635 blocked
      these effects, indicating that the neuroprotective properties of repinotan are
      mediated through the 5-HT1A receptor. The proposed neuroprotective mechanisms of
      repinotan are thought to be the result of neuronal hyperpolarization via the
      activation of G protein-coupled inwardly rectifying K+ channels upon binding to
      both pre- and post-synaptic 5-HT1A receptors. Hyperpolarization results in
      inhibition of neuron firing and reduction of glutamate release. These mechanisms,
      leading to protection of neurons against overexcitation, could explain the
      neuroprotective efficacy of repinotan per se, but not necessarily the efficacy by
      delayed administration. The therapeutic time window of repinotan appeared to be
      at least 5 h in in vivo animal models, but may be even longer at higher doses of
      the drug. Experimental studies indicate that repinotan affects various mechanisms
      involved in the pathogenesis of brain injury. In addition to the direct effect of
      repinotan on neuronal hyperpolarization and suppression of glutamate release this
      compound affects the death-inhibiting protein Bcl-2, serotonergic glial growth
      factor S-100beta and Nerve Growth Factor. It also suppresses the activity of
      caspase-3 through MAPK and PKCalpha; this effect may contribute to its
      neuroprotective efficacy. The dose- and time-dependent neuroprotective efficacy
      of repinotan indicates that the drug is a promising candidate for prevention of
      secondary brain damage in brain-injured patients suffering from acute ischemic
      stroke. Unfortunately, however, the first, randomized, double blind, placebo
      controlled clinical trial did not demonstrate the efficacy of repinotan in acute
      ischemic stroke.

PMID- 16614739
TI  - Molecular virology of hepatitis C virus (HCV): 2006 update.
AB  - Fascinating progress in the understanding of the molecular biology of hepatitis C
      virus (HCV) was achieved recently. The replicon system revolutionized the
      investigation of HCV RNA replication and facilitated drug discovery. Novel
      systems for functional analyses of the HCV glycoproteins allowed the validation
      of HCV receptor candidates and the investigation of cell entry mechanisms. Most
      recently, recombinant infectious HCV could be produced in cell culture, rendering
      all steps of the viral life cycle, including entry and release of viral
      particles, amenable to systematic analysis. In this review, we summarize recent
      advances and discuss future research directions.

PMID- 16614740
TI  - Hepatitis C virus serologic and virologic tests and clinical diagnosis of HCV
      related liver disease.
AB  - The use of serological and virological tests has become essential in the
      management of hepatitis C virus (HCV) infection in order to diagnose infection,
      guide treatment decisions and assess the virological response to antiviral
      therapy. Virological tools include serological assays for anti-HCV antibody
      detection and serological determination of the HCV genotype, and molecular assays
      that detect and quantify HCV RNA and determine the HCV genotype. Anti-HCV
      antibody testing and HCV RNA testing are used to diagnose acute and chronic
      hepatitis C. Only patients with detectable HCV RNA should be considered for
      pegylated interferon alfa and ribavirin therapy and the HCV genotype should be
      systematically determined before treatment, as it determines the indication, the
      duration of treatment, the dose of ribavirin and the virological monitoring
      procedure. HCV RNA monitoring during therapy is used to tailor treatment duration
      in HCV genotype 1 infection, and molecular assays are used to assess the end-of
      treatment and, most importantly the sustained virological response, i.e. the
      endpoint of therapy.

PMID- 16614741
TI  - Epidemiology of hepatitis C virus (HCV) infection.
AB  - Hepatitis C virus remains a large health care burden to the world. Incidence
      rates across the world fluctuate and are difficult to calculate given the
      asymptomatic, often latent nature of the disease prior to clinical presentation.
      Prevalence rates across the world have changed as well with more countries aware
      of transfusion-related hepatitis C and more and more evidence supporting
      intravenous drug use as the leading risk factor of spread of the virus. This
      article reviews current hepatitis C virus prevalence and genotype data and
      examines the different risk factors associated with the virus.

PMID- 16614742
TI  - The natural history of hepatitis C virus (HCV) infection.
AB  - Hepatitis C virus (HCV) is a leading cause of chronic liver disease, cirrhosis,
      and hepatocellular carcinoma, as well as the most common indication for liver
      transplantation in many countries. Although the incidence of hepatitis C
      infection has dramatically decreased during the past decade, the worldwide
      reservoir of chronically infected persons is estimated at 170 million, or 3% of
      the global population. There is much controversy surrounding the natural history
      of hepatitis C infection. The rate of chronic HCV infection is affected by a
      person's age, gender, race, and viral immune response. Approximately 75%-85% of
      HCV-infected persons will progress to chronic HCV infection, and are at risk for
      the development of extrahepatic manifestations, compensated and decompensated
      cirrhosis, and hepatocellular carcinoma (HCC). The rate of progression to
      cirrhosis is highly variable, and is influenced by several factors, including the
      amount of alcohol consumption, age of initial HCV infection, degree of
      inflammation and fibrosis on liver biopsy, HIV and HBV coinfection, and comordid
      conditions. An estimated 10%-15% of HCV-infected persons will advance to
      cirrhosis within the first 20 years. Persons with cirrhosis are at increased risk
      of developing HCC. An understanding of the natural history of hepatitis C is
      essential to effectively manage, treat, and counsel individuals with HCV
      infection.

PMID- 16614743
TI  - Hepatitis C virus (HCV) infection and hepatic steatosis.
AB  - There are two discrete forms of steatosis that may be found in patients infected
      with hepatitis C virus (HCV). Metabolic steatosis can coexist with HCV,
      regardless of genotype, in patients with risk factors such as obesity,
      hyperlipidemia, and insulin resistance. The second form of hepatic steatosis in
      HCV patients is a result of the direct cytopathic effect of genotype 3 viral
      infections. There have been proposed mechanisms for this process but it remains
      elusive. Both categories of steatosis tend to hasten the progression of liver
      fibrosis and therefore prompt recognition and management should be initiated in
      patients with HCV and steatosis. The authors review the current understanding of
      the relationship between hepatitis C infection and hepatic steatosis and discuss
      future research directions.

PMID- 16614744
TI  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) dual infection.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections account for a
      substantial proportion of liver diseases worldwide. Because the two hepatotropic
      viruses share same modes of transmission, coinfection with the two viruses is not
      uncommon, especially in areas with a high prevalence of HBV infection and among
      people at high risk for parenteral infection. Patients with dual HBV and HCV
      infection have more severe liver disease, and are at an increased risk for
      progression to hepatocellular carcinoma (HCC). Treatment of viral hepatitis due
      to dual HBV/HCV infection represents a challenge.

PMID- 16614745
TI  - A practical approach to managing patients with HCV infection.
AB  - Hepatitis C virus (HCV) infection is a major worldwide public health concern. It
      is a common cause of chronic liver disease and hepatocellular carcinoma. HCV
      antibody and HCV RNA testing are available diagnostic studies that offer high
      degree of accuracy. Current standard therapy includes a combination of pegylated
      interferon and ribavirin. Response rate is approximately 40% for genotype 1 and
      80% for genotypes 2 and 3, respectively. Successful treatment can stop the
      progression of chronic liver disease, reduce the need for liver transplantation,
      and possibly decrease the risk for Hepatocellular carcinoma (HCC). Evaluating for
      potential treatment candidacy is an important initial step in the management of
      chronic HCV infection as not all individuals may need or qualify for the
      treatment. Understanding the natural history, the different diagnostic
      modalities, the current therapeutic options and, the treatment response and
      adverse effect profiles can help the practitioners better manage chronic HCV
      infection.

PMID- 16614746
TI  - Treatment of chronic HCV infection in special populations.
AB  - The mainstay of treatment of chronic hepatitis C is pegylated interferon combined
      with ribavirin and more than 50% of naive patients will have viral cure with
      either 6 months (genotypes 2 and 3) or 12 months (genotypes 1,4, and 6) with the
      initial treatment. However, populations have been defined that respond less well
      to routine treatment including African Americans, immune suppressed populations,
      obese patients and cirrhotic patients. These types of patients are enriched in
      groups of patients who are non-responders to treatment. This article discusses
      viral kinetics that may impact treatment response, strategies to maximize
      treatment effectiveness in these populations and the treatment of non-responders
      in general. Early viral kinetics can be used to define response or non-response
      and these results can be used to modify subsequent treatment length and dose.

PMID- 16614747
TI  - Antiviral therapy of HCV in the cirrhotic and transplant candidate.
AB  - Despite the improved efficacy of peginterferons, the rate of sustained virologic
      response is suboptimal in cirrhotic patients, relative to non-cirrhotic patients.
      However, the treatment of patients with compensated cirrhosis has recently been
      encouraged by expert panels. Interferon-based therapy may provide additional
      benefit by reducing the risk of hepatocellular carcinoma in cirrhotic patients as
      suggested in preliminary studies. Results of two ongoing prospective studies are
      awaited to answer the important question of the effectiveness of suppressive
      interferon therapy, even in the absence of sustained virologic response. Given
      the importance of recurrent HCV following liver transplantation, attention has
      been directed toward the antiviral treatment of patients with advanced liver
      disease. This approach needs to be pursued with caution given the potential
      morbidity of the therapy. Recently, a low accelerating dosage regimen has
      provided excellent results and is the subject of additional inquiry.

PMID- 16614748
TI  - Management of HCV infection and liver transplantation.
AB  - A major challenge facing liver transplant recipients and their physicians is
      recurrence of hepatitis C virus infection following otherwise technically
      successful liver transplantation. Recurrent infection leads to diminished graft
      and patient survival. Although a number or predictors of severe recurrence have
      been identified, no definitive strategy has been developed to prevent recurrence.
      Generally the tempo of hepatitis C recurrence is gauged by serial liver biopsies
      with the decision to intervene with antiviral therapy based on local philosophy
      and expertise. Treating hepatitis C in this population has a number of major
      challenges including diminished patient tolerance for side-effects as well as
      managing the patient's immunesuppression. However sustained viral responses are
      possible with the potential to reduce the impact of recurrent hepatitis on the
      graft. However recurrent hepatitis C virus infection will remain the most
      frequent form of recurrent disease in liver transplant programs for the
      foreseeable future.

PMID- 16614749
TI  - DESCRIPTIVE ANALYSIS OF DIVALENT SALTS.
AB  - Many divalent salts (e.g., calcium, iron, zinc), have important nutritional value
      and are used to fortify food or as dietary supplements. Sensory characterization
      of some divalent salts in aqueous solutions by untrained judges has been reported
      in the psychophysical literature, but formal sensory evaluation by trained panels
      is lacking. To provide this information, a trained descriptive panel evaluated
      the sensory characteristics of 10 divalent salts including ferrous sulfate,
      chloride and gluconate; calcium chloride, lactate and glycerophosphate; zinc
      sulfate and chloride; and magnesium sulfate and chloride. Among the compounds
      tested, iron compounds were highest in metallic taste; zinc compounds had higher
      astringency and a glutamate-like sensation; and bitterness was pronounced for
      magnesium and calcium salts. Bitterness was affected by the anion in ferrous and
      calcium salts. Results from the trained panelists were largely consistent with
      the psychophysical literature using untrained judges, but provided a more
      comprehensive set of oral sensory attributes.

PMID- 16614752
TI  - The effective temperature of Peptide ions dissociated by sustained off-resonance
      irradiation collisional activation in fourier transform mass spectrometry.
AB  - A method for determining the internal energy of biomolecule ions activated by
      collisions is demonstrated. The dissociation kinetics of protonated leucine
      enkephalin and doubly protonated bradykinin were measured using sustained off
      resonance irradiation (SORI) collisionally activated dissociation (CAD) in a
      Fourier transform mass spectrometer. Dissociation rate constants are obtained
      from these kinetic data. In combination with Arrhenius parameters measured with
      blackbody infrared radiative dissociation, the "effective" temperatures of these
      ions are obtained. Effects of excitation voltage and frequency and the ion cell
      pressure were investigated. With typical SORI-CAD experimental conditions, the
      effective temperatures of these peptide ions range between 200 and 400 degrees C.
      Higher temperatures can be easily obtained for ions that require more internal
      energy to dissociate. The effective temperatures of both protonated leucine
      enkephalin and doubly protonated bradykinin measured with the same experimental
      conditions are similar. Effective temperatures for protonated leucine enkephalin
      can also be obtained from the branching ratio of the b(4) and (M + H - H(2)O)(+)
      pathways. Values obtained from this method are in good agreement with those
      obtained from the overall dissociation rate constants. Protonated leucine
      enkephalin is an excellent "thermometer" ion and should be well suited to
      establishing effective temperatures of ions activated by other dissociation
      techniques, such as infrared photodissociation, as well as ionization methods,
      such as matrix assisted laser desorption/ionization.

PMID- 16614753
TI  - Glial cell inclusions and the pathogenesis of neurodegenerative diseases.
AB  - In this review, we discuss examples that show how glial-cell pathology is
      increasingly recognized in several neurodegenerative diseases. We also discuss
      the more provocative idea that some of the disorders that are currently
      considered to be neurodegenerative diseases might, in fact, be due to primary
      abnormalities in glia. Although the mechanism of glial pathology (i.e. modulating
      glutamate excitotoxicity) might be better established for amyotrophic lateral
      sclerosis (ALS), a role for neuronal-glial interactions in the pathogenesis of
      most neurodegenerative diseases is plausible. This burgeoning area of
      neuroscience will receive much attention in the future and it is expected that
      further understanding of basic neuronal-glial interactions will have a
      significant impact on the understanding of the fundamental nature of human
      neurodegenerative disorders.

PMID- 16614754
TI  - Narrowed TCR repertoire and viral escape as a consequence of heterologous
      immunity.
AB  - Why some virus-specific CD8 TCR repertoires are diverse and others restricted or
      "oligoclonal" has been unknown. We show here that oligoclonality and extreme
      clonal dominance can be a consequence of T cell cross-reactivity. Lymphocytic
      choriomeningitis virus (LCMV) and Pichinde virus (PV) encode NP(205-212) epitopes
      that induce different but highly cross-reactive diverse TCR repertoires.
      Homologous viral challenge of immune mice only slightly skewed the repertoire and
      enriched for predictable TCR motifs. However, heterologous viral challenge
      resulted in a narrow oligoclonal repertoire with dominant clones with
      unpredictable TCR sequences. This shift in clonal dominance varied with the
      private, i.e., unique, specificity of the host's TCR repertoire and was simulated
      using affinity-based computer models. The skewing differences in TCR repertoire
      following homologous versus heterologous challenge were observed within the same
      private immune system in mice adoptively reconstituted with memory CD8 T cell
      pools from the same donor. Conditions driving oligoclonality resulted in an LCMV
      epitope escape variant in vivo resembling the natural Lassa virus sequence. Thus,
      T cell oligoclonality, including extremes in clonal dominance, may be a
      consequence of heterologous immunity and lead to viral escape. This has
      implications for the design of peptide-based vaccines, which might
      unintentionally prime for skewed TCR responses to cross-reactive epitopes.

PMID- 16614755
TI  - Spare guanylyl cyclase NO receptors ensure high NO sensitivity in the vascular
      system.
AB  - In the vascular system, the receptor for the signaling molecule NO, guanylyl
      cyclase (GC), mediates smooth muscle relaxation and inhibition of platelet
      aggregation by increasing intracellular cyclic GMP (cGMP) concentration. The
      heterodimeric GC exists in 2 isoforms (alpha1-GC, alpha2-GC) with
      indistinguishable regulatory properties. Here, we used mice deficient in either
      alpha1- or alpha2-GC to dissect their biological functions. In platelets, alpha1
      GC, the only isoform present, was responsible for NO-induced inhibition of
      aggregation. In aortic tissue, alpha1-GC, as the major isoform (94%), mediated
      vasodilation. Unexpectedly, alpha2-GC, representing only 6% of the total GC
      content in WT, also completely relaxed alpha1-deficient vessels albeit higher NO
      concentrations were needed. The functional impact of the low cGMP levels produced
      by alpha2-GC in vivo was underlined by pronounced blood pressure increases upon
      NO synthase inhibition. As a fractional amount of GC was sufficient to mediate
      vasorelaxation at higher NO concentrations, we conclude that the majority of NO
      sensitive GC is not required for cGMP-forming activity but as NO receptor reserve
      to increase sensitivity toward the labile messenger NO in vivo.

PMID- 16614756
TI  - Cyclooxygenases, microsomal prostaglandin E synthase-1, and cardiovascular
      function.
AB  - We investigated the mechanisms by which inhibitors of prostaglandin G/H synthase
      2 (PGHS-2; known colloquially as COX-2) increase the incidence of myocardial
      infarction and stroke. These inhibitors are believed to exert both their
      beneficial and their adverse effects by suppression of PGHS-2-derived
      prostacyclin (PGI(2)) and PGE(2). Therefore, the challenge remains to identify a
      mechanism whereby PGI(2) and PGE(2) expression can be suppressed while avoiding
      adverse cardiovascular events. Here, selective inhibition, knockout, or mutation
      of PGHS-2, or deletion of the receptor for PGHS-2-derived PGI(2), was shown to
      accelerate thrombogenesis and elevate blood pressure in mice. These responses
      were attenuated by COX-1 knock down, which mimics the beneficial effects of low
      dose aspirin. PGE(2) biosynthesis is catalyzed by the coordinate actions of COX
      enzymes and microsomal PGE synthase-1 (mPGES-1). We show that deletion of mPGES-1
      depressed PGE(2) expression, augmented PGI(2) expression, and had no effect on
      thromboxane biosynthesis in vivo. Most importantly, mPGES-1 deletion affected
      neither thrombogenesis nor blood pressure. These results suggest that inhibitors
      of mPGES-1 may retain their antiinflammatory efficacy by depressing PGE(2), while
      avoiding the adverse cardiovascular consequences associated with PGHS-2-mediated
      PGI(2) suppression.

PMID- 16614757
TI  - Placental growth factor mediates mesenchymal cell development, cartilage
      turnover, and bone remodeling during fracture repair.
AB  - Current therapies for delayed- or nonunion bone fractures are still largely
      ineffective. Previous studies indicated that the VEGF homolog placental growth
      factor (PlGF) has a more significant role in disease than in health. Therefore we
      investigated the role of PlGF in a model of semi-stabilized bone fracture
      healing. Fracture repair in mice lacking PlGF was impaired and characterized by a
      massive accumulation of cartilage in the callus, reminiscent of delayed- or
      nonunion fractures. PlGF was required for the early recruitment of inflammatory
      cells and the vascularization of the fracture wound. Interestingly, however, PlGF
      also played a role in the subsequent stages of the repair process. Indeed in vivo
      and in vitro findings indicated that PlGF induced the proliferation and
      osteogenic differentiation of mesenchymal progenitors and stimulated cartilage
      turnover by particular MMPs. Later in the process, PlGF was required for the
      remodeling of the newly formed bone by stimulating osteoclast differentiation. As
      PlGF expression was increased throughout the process of bone repair and all the
      important cell types involved expressed its receptor VEGFR-1, the present data
      suggest that PlGF is required for mediating and coordinating the key aspects of
      fracture repair. Therefore PlGF may potentially offer therapeutic advantages for
      fracture repair.

PMID- 16614758
TI  - Optimization of a self antigen for presentation of multiple epitopes in cancer
      immunity.
AB  - T cells recognizing self antigens expressed by cancer cells are prevalent in the
      immune repertoire. However, activation of these autoreactive T cells is limited
      by weak signals that are incapable of fully priming naive T cells, creating a
      state of tolerance or ignorance. Even if T cell activation occurs, immunity can
      be further restricted by a dominant response directed at only a single epitope.
      Enhanced antigen presentation of multiple epitopes was investigated as a strategy
      to overcome these barriers. Specific point mutations that create altered peptide
      ligands were introduced into the gene encoding a nonimmunogenic tissue self
      antigen expressed by melanoma, tyrosinase-related protein-1 (Tyrp1). Deficient
      asparagine-linked glycosylation, which was caused by additional mutations,
      produced altered protein trafficking and fate that increased antigen processing.
      Immunization of mice with mutated Tyrp1 DNA elicited cross-reactive CD8(+) T cell
      responses against multiple nonmutated epitopes of syngeneic Tyrp1 and against
      melanoma cells. These multi-specific anti-Tyrp1 CD8(+) T cell responses led to
      rejection of poorly immunogenic melanoma and prolonged survival when immunization
      was started after tumor challenge. These studies demonstrate how rationally
      designed DNA vaccines directed against self antigens for enhanced antigen
      processing and presentation reveal novel self epitopes and elicit multi-specific
      T cell responses to nonimmunogenic, nonmutated self antigens, enhancing immunity
      against cancer self antigens.

PMID- 16614759
TI  - A step forward for Brazilian pediatric research.

PMID- 16614760
TI  - Surface electromyography of facial muscles during natural and artificial feeding
      of infants: identification of differences between breast-, cup- and bottle
      feeding.

PMID- 16614761
TI  - Systematic literature review of modifiable risk factors for recurrent acute
      otitis media in childhood.
AB  - OBJECTIVE: Review evidence about modifiable risk factors for recurrent acute
      otitis media. SOURCE OF DATA: MEDLINE with no language restriction, from January
      1966 to July 2005, using descriptors "acute otitis media/risk factors". Two
      hundred and fifty-seven articles were obtained. These included randomized
      clinical trials, cohorts, case-control and cross-sectional studies that contained
      analyses of modifiable risk factors for the development of recurrent acute otitis
      media as the main objective and with samples of individuals up to the age of 18
      years. Except when relevant, the following were excluded: non-systematic reviews,
      reports of cases, series of cases, and medical society guidelines. SUMMARY OF
      DATA: Nine risk factors linked to the host and eight linked to the environment
      were identified. Of the first group, allergy, craniofacial abnormalities,
      gastroesophageal reflux and the presence of adenoids were classified as
      modifiable. In the second category, upper airway infections, day care center
      attendance, presence of siblings/family size, passive smoking, breastfeeding and
      use of pacifiers were included. Afterwards, the risk factors were classified in
      accordance with levels of evidence. CONCLUSIONS: The risk factors established for
      recurrent acute otitis media and capable of being modified were the use of
      pacifiers and care in daycare centers. The probable risk factors were privation
      of mother's milk, presence of siblings, craniofacial abnormalities, passive
      smoking and presence of adenoids. No modifiable factor was classified as
      unlikely. Among those that need further study are allergy, gastroesophageal
      reflux and passive smoking during gestation.

PMID- 16614762
TI  - Brazilian knowledge production in the field of child and adolescent health.
AB  - OBJECTIVES: To assess (a) the trend of MEDLINE citation of pediatrics articles
      associated with Brazilian institutions from 1990 through 2004; (b) the number of
      Brazilian pediatrics articles published in journals with the highest impact
      factor; and (c) the regional distribution of institutions. METHODS: PubMed search
      limited to ages 0 to 18 years, English language, MEDLINE and humans subsets,
      Brazilian affiliation. For each year, we compared the articles retrieved to the
      whole of MEDLINE citations with the same search limits, except for affiliation,
      as well as to the total Brazilian scientific production cited in MEDLINE, without
      age limits. We made a descriptive analysis, and used the chi-square test for
      trend. Data concerning publication in journals with the highest impact factor
      were aggregated into three-year periods. RESULTS: A total of 7,222 Brazilian
      pediatrics articles were listed in MEDLINE from 1990 through 2004, corresponding
      to 0.95% of all articles concerning the age group from 0 to 18 years. There was a
      fivefold increase in the absolute number of Brazilian articles along the study
      period. The ratio of Brazilian to total articles increased from 0.51 to 1.60% (p
      < 0.01). Scientific knowledge production remains strongly concentrated in the
      Southeast of Brazil. CONCLUSION: Brazilian research activities in pediatrics have
      had a steady upward trend, which relates to the proportional growth of the
      Brazilian scientific production as a whole.

PMID- 16614763
TI  - Surface electromyography of facial muscles during natural and artificial feeding
      of infants.
AB  - OBJECTIVE: To measure and compare the activity of the masseter, temporalis and
      buccinator muscles in different infant feeding methods. METHOD: Cross-sectional
      study of 60 full-term infants with no intercurrent diseases, aged between two and
      three months, classified into the following groups: 1) exclusive breastfeeding;
      2) breastfeeding plus bottle-feeding; and 3) exclusive breastfeeding plus cup
      feeding. Surface electromyography was performed during infant feeding. The
      Krushal-Wallis test was used, complemented by multiple paired comparisons of the
      groups. A 5% significance level was chosen for the tests. RESULTS: Statistically
      higher results were verified in the breastfeeding group in relation to the bottle
      feeding one, both in the range of movement and the mean contraction of the
      masseter. With regard to the temporalis muscle, statistically higher results were
      found in the breastfeeding group comparatively to the bottle-feeding one. As to
      the buccinator muscle, statistically higher results were observed in the
      breastfeeding group in relation to the bottle-feeding one, although in this case,
      the difference concerned only the range of contraction. CONCLUSION: The
      similarities between the muscle activity in the breastfeeding and in the cup
      feeding groups suggests that cup-feeding can be used as an alternative infant
      feeding method, being better than bottle-feeding, due to the hyperactivity of the
      buccinator muscle, which could result in changes to the structural growth and
      development of the stomatognathic system functions.

PMID- 16614764
TI  - Hearing screening in a neonatal intensive care unit.
AB  - OBJECTIVE: Investigate the prevalence of hearing impairment in newborns
      hospitalized at the Intensive and Intermediate Care Unit at the Women's
      Comprehensive Health Center Neonatology Service (UNICAMP) and associated risk
      factors. METHODS: 979 newborn babies were assessed between January 2000 and
      January 2003, through automated auditory brainstem response (AABR) (ALGO 2e color
      screener). The result was considered normal when the newborn showed response to a
      35dBNA signal bilaterally. The prevalence of AABR impairment and the odds ratio
      were analyzed with a 95% confidence interval using bivariate analysis. To
      identify the independent risk factors for hearing alterations, multivariate
      analyses were used with logistic regression. RESULTS: The prevalence of AABR
      impairment was 10.2%, of which 5.3% was unilateral and 4.9% bilateral. From the
      multivariate analyses, the following observations were made: family history of
      congenital hearing loss (OR = 5.192; p = 0.016), craniofacial deformity (OR =
      5.530; p < 0.001), genetic syndromes associated with hearing loss (OR = 4.212; p
      < 0.001), weight below 1,000 g (OR = 3.230; p < 0.001), asphyxia (OR = 3.532; p <
      0.001), hyperbilirubinemia (OR = 4.099; p = 0.002) and use of mechanical
      ventilation (OR = 1.826; p < 0.031) were the indicators that best characterized
      the group at risk for hearing impairment. CONCLUSIONS: The prevalence of hearing
      impairment using AABR is high. Therefore, it is essential for all newborns who
      present isolated or associated risk factors to undergo hearing screening in
      situations in which it is not possible to have universal hearing screening.

PMID- 16614765
TI  - Undergraduate teaching of pediatrics in medical schools of the state of Rio de
      Janeiro.
AB  - OBJECTIVE: The aim of this study is to describe and analyze the teaching of
      pediatrics in medical schools of the state of Rio de Janeiro in terms of
      structure, hour load, insertion into the Medical course curriculum, objectives,
      syllabuses, learning scenarios, and evaluation methods. METHODS: A cross
      sectional study of 16 pediatric courses of medical schools of the state of Rio de
      Janeiro was carried out using exploratory and descriptive research methods. The
      data were obtained at the investigated schools from the Teaching Coordinators of
      the Pediatric courses, and institutional documents were also analyzed. RESULTS:
      The insertion of pediatric education into the Medical course curriculum, the
      learning environments and the criteria for the selection of contents were not so
      different among the investigated courses. Pediatric education corresponds to
      10.07% of the total hour load of the medical course; this rate is very close to
      the one recommended by Southern Cone pediatric associations. Pediatric medical
      education begins in the third year in most of the undergraduate courses.
      Cognitive development in the learning process and student-centered evaluation,
      predominantly based on written tests, are highlighted. Among the analyzed
      courses, the percentage of practical activities ranges from 0 to 60% in the pre
      internship period. CONCLUSIONS: The teaching of pediatrics in medical schools of
      the state of Rio de Janeiro gives priority to general medical education; in the
      pre-internship period, expositive lectures prevail; primary health care settings
      are used; evaluation is focused on written tests, placing special emphasis on
      cognitive aspects in most courses.

PMID- 16614766
TI  - Factors associated with risk of low folate intake among adolescents.
AB  - OBJECTIVE: To evaluate factors associated with the risk of low folate intake
      among adolescents. METHODS: We employed cluster sampling, using a random
      selection of 40 representative census sectors and households within those
      sectors, including all individuals between 10 and 19 years of age. The weight,
      height and skin folds of subjects were measured and socioeconomic data on their
      families were collected. A 24-hour dietary recall and frequency questionnaire
      were used to estimate the quantity and frequency of folate intake. Folate
      consumption was quantified using Nutwin software. Risk of low folate intake was
      defined as Folate consumption below the estimated average requirement. The
      statistical analysis employed hierarchical logistic regression. RESULTS: A total
      of 722 adolescents were investigated and their mean folate intake was 145+/-117
      microg. The frequency of subjects at risk of having a lower than recommended
      folate intake was 89%. Adolescents had a greater risk of inadequate folate intake
      if their body mass index was at or above the 85th percentile, their waist
      circumference was at or above the 80th percentile or they had a family history of
      cardiovascular disease. Adolescents who ate beans and dark green vegetables less
      than four times a week also exhibited an increased chance of having folate intake
      below recommended levels. CONCLUSIONS: These adolescents present a high risk of
      low folate intake and this risk is linked with increasing age, waist
      circumference above the 80th percentile and low frequency of beans and dark green
      vegetables consumption.

PMID- 16614767
TI  - Endoscopic dilatation of esophageal strictures in children and adolescents.
AB  - OBJECTIVE: To assess the causes of esophageal stricture in pediatric patients and
      their response to endoscopic dilatation. METHODS: Retrospective analysis of
      clinical and endoscopic data obtained from children and adolescents with
      esophageal stricture submitted to endoscopic dilatation between July 1993 and
      January 2003. RESULTS: A total of 125 patients aged between 1 month and 16 years
      were included in the study. Among the types of stenosis, postoperative (43.2%),
      corrosive (27.2%) and peptic (21.6%) strictures were the most prevalent. Those
      patients with corrosive esophageal stricture needed more dilatation sessions.
      Five cases of esophageal perforation and one case of hemorrhage occurred due to
      complications during the procedure. Good response to endoscopic treatment was
      described in 74.4% of cases, but better results were obtained from patients with
      peptic esophageal stricture. CONCLUSIONS: Endoscopic treatment of esophageal
      strictures in children and adolescents yields good results and has a low rate of
      complications. Corrosive esophageal strictures have a higher morbidity and
      require more dilatation sessions.

PMID- 16614769
TI  - Prevalence of allergic rhinitis among adolescents from Distrito Federal, Brazil:
      comparison between ISAAC phases I and III.
AB  - OBJECTIVE: To determine the prevalence of allergic rhinitis in a random group of
      schoolchildren aged 13 to 14 years in Brasilia, Brazil, to evaluate tendencies
      over 6 years and to compare prevalence rates among different socioeconomic
      groups. METHODS: Two cross-sectional studies were undertaken 6 years apart, using
      the ISAAC (phases I and III) written questionnaire. Thirty-nine schools were
      chosen at random from eight administrative regions in Brasilia, and were
      classified into three groups according to the socioeconomic conditions of the
      population. RESULTS: A total of 3,009 questionnaires were collected. Of these
      53.5% related to female children and 80% to students from public schools.
      Prevalence rates for diagnosed rhinitis, recent rhinitis and allergic rhinitis
      were 20, 29.3 and 12.2%, respectively. Rhinitis was more prevalent in private
      schools than in public ones (17.8 versus 14.1%) and sufferers were predominantly
      female. Prevalence rates were also higher among populations with higher
      socioeconomic status (23.5 versus 12.2%). Comparison with the 1996 data revealed
      significant increases in the prevalence of diagnosed rhinitis (12.7 versus 20%, p
      = 0.001). These increases were observed at all socioeconomic levels. CONCLUSIONS:
      A large number of 13 and 14-year-old children resident in the Distrito Federal
      exhibit symptoms indicative of rhinitis and the majority of them have allergic
      rhinitis. Over a six-year period the prevalence of allergic rhinitis increased
      significantly, predominantly affecting females and with greater prevalence among
      students at private school and from families with higher socioeconomic status.

PMID- 16614768
TI  - Response to polysaccharide antigens in patients with ataxia-telangiectasia.
AB  - OBJECTIVE: To analyze the production of antibodies to polysaccharide antigens in
      patients with ataxia-telangiectasia. PATIENTS AND METHODS: We used the ELISA
      technique to measure the levels of IgG antibodies to serotypes 1, 3, 5, 6B, 9V
      and 14 of Streptococcus pneumoniae in 14 patients with ataxia-telangiectasia
      before and after immunization with 23-valent polysaccharide vaccine. Adequate
      response to individual polysaccharide can be defined as a postimmunization
      antibody titer equal to or greater than 1.3 microg/ml or as a minimum fourfold
      increase over the baseline (preimmunization) value. RESULTS: Six (43%) patients
      showed an absent response to all serotypes analyzed. Four patients showed
      adequate response to only one serotype, one patient to two serotypes, two
      patients to three serotypes and only one patient to four out of six serotypes
      analyzed. No patient had adequate response to all serotypes tested.
      Postimmunization pneumococcus IgG levels were higher than preimmunization levels
      to all serotypes analyzed, except for serotype 3. In spite of this, the mean
      postimmunization levels were lower than 1.3 microg/ml in all serotypes, except
      for serotype 14. Mean increment was less than four in all serotypes analyzed.
      CONCLUSIONS: Our results suggest that patients with ataxia-telangiectasia are at
      a high risk of having an impaired response to pneumococcus, which may be one of
      the causes of recurrent sinopulmonary infections in these patients.

PMID- 16614770
TI  - Pulmonary function assessment in children and teenagers before and after surgical
      treatment for rheumatic valve disease.
AB  - OBJECTIVE: To assess pulmonary function in children and adolescents subjected to
      correction of rheumatic valve disease in order to quantify changes caused by
      factors inherent to surgery and rheumatic heart disease. METHODS: This was a
      longitudinal and quantitative intervention study, undertaken at a children's
      hospital that is a center of excellence for the state of Pernambuco (Instituto
      Materno Infantil de Pernambuco), between December 2004 and May 2005. Eighteen
      children suffering from rheumatic fever and indicated for surgery to repair or
      replace the mitral valve were assessed preoperatively and again on the first and
      fifth postoperative days. The parameters recorded were minute volume, rapid
      shallow breathing index, peak expiratory flow, forced vital capacity and
      inspiratory capacity. RESULTS: All patients were aged 8 to 17 years (mean 12.4+/
      2.1), they had a mean body mass index of 16.1+/-2.2, and were weaned off invasive
      mechanical ventilation during the first 10 postoperative hours. All parameters
      had undergone significant deterioration on the first day (statistically
      significant, p < or = 0.01), demonstrating gradual improvement up to the last day
      of assessment, although, with the exception of minute volume which was no longer
      significantly different from the fourth day onwards (p > 0.01), without returning
      to baseline levels. CONCLUSION: We observed that the pulmonary dysfunction that
      results from this type of heart surgery is maintained until at least the fifth
      postoperative day. It appears that this dysfunction is influenced by the pain and
      mechanical alterations caused by sternotomy and reduced pulmonary compliance post
      surgery.

PMID- 16614771
TI  - Linguistic validation of cystic fibrosis quality of life questionnaires.
AB  - OBJECTIVE: The purpose of this study was to validate the Portuguese translations
      of four cystic fibrosis quality of life questionnaires (CFQ). The first three
      were developed for patients with cystic fibrosis aged from 6 to 11 years, from 12
      to 13 years and 14 years or more, while the fourth was developed for the parents
      of patients aged 6 to 13 years. MATERIAL AND METHODS: The four CFQ translations
      contained from 35 to 50 questions covering nine domains and were validated as
      follows: translation from English to Portuguese, pilot application, back
      translation and then approval by the author of the English versions. The four
      translations were applied to 90 stable patients (30 from each age group) and the
      parents of patients aged 6-13 years (n = 60), on two occasions with a 13 to 17
      day interval. Intraclass Correlation Coefficients (ICC) were used to measure
      reproducibility. This study was approved by the Commission for Ethics in Research
      at the institution. RESULTS: Reproducibility was good (ICC = 0.62 to 0.99) for
      the four translations in all domains, with the exceptions of the Digestion domain
      for the 6 to 11 and 12 to 13 years age groups with ICC = 0.59 and 0.47,
      respectively and the Social Role domain for the 14 and over age group (ICC = 
      0.19 ). CONCLUSION: The translation and cultural adaptation for Brazil resulted
      in four CFQ versions that are easy to understand and offer good reproducibility.

PMID- 16614772
TI  - Central pontine and extrapontine myelinolysis: report of a case with a tragic
      outcome.
AB  - OBJECTIVE: To report a pediatric case of central pontine and extrapontine
      myelinolysis, a rare neurological disease often associated with rapid correction
      of hyponatremia. DESCRIPTION: A 15 year-old female adolescent developed locked-in
      syndrome during severe hyponatremia. Brain magnetic resonance imaging was
      consistent with the diagnosis of central pontine and extrapontine myelinolysis.
      COMMENTS: Serum sodium correction should proceed slowly and cautiously, based
      upon a careful calculation of sodium deficit, in order to minimize metabolic
      stress and avoid the occurrence of this dreadful complication, which has a tragic
      outcome in most cases. There is no scientifically proved effective treatment for
      myelinolysis, and severe cases usually have a dismal prognosis.

PMID- 16614774
TI  - Rhinovirus and bronchiolitis.

PMID- 16614776
TI  - Cow's milk, infant formula and iron-deficiency anemia.

PMID- 16614779
TI  - Controlled dose delivery in topical treatment of anal fissure: pilot study of a
      new paradigm.
AB  - PURPOSE: Topical nitroglycerin has been widely used as a means for avoiding
      surgery in patients with anal fissure. However, nitroglycerin has not been
      universally accepted for this application because of inconsistency of efficacy
      and side effects. This study compares conventional digital application with
      precise intra-anal dosing of nitroglycerin using a specialized dose-delivery
      device and anal cannula. METHODS: Twenty-six consecutive patients (13 males) with
      chronic anal fissure and no previous treatment were randomly allocated to receive
      0.75 ml of 0.3 percent nitroglycerin ointment (2.25 mg nitroglycerin) t.i.d.
      intra-anal using the cannula (Group A) or perianally with the gloved finger
      (Group B). Nitroglycerin dosage was controlled in Group A by the dose-delivery
      device connected to the cannula and by single-dose preloaded syringes in Group B.
      RESULTS: Anal manometry: pressure reduction after application of nitroglycerin
      was 47 +/- 18.6 in Group A and 20.7 +/- 13.4 percent in Group B (P < 0.01).
      Headaches were reported by 1 of 10 patients in Group A and 10 of 12 patients in
      Group B (P = 0.0027). Seven patients of Group B had to be crossed to intra-anal
      treatment as a result of intensity of headaches. Pain relief was noted by 8 of 10
      and 9 of 12 patients in Groups A and B, respectively (P = 0.6). Sphincterotomy
      was required in only 13.6 percent of all patients. CONCLUSIONS: Controlled intra
      anal dosing of topical nitroglycerin produces a significantly greater reduction
      in sphincteric pressure and lower incidence of headaches than with perianal
      administration of the same dose of ointment. These results suggest a new paradigm
      for increasing safety and efficacy of dose-dependent prescription anal topical
      medications.

PMID- 16614778
TI  - Gene expression and genetic mapping analyses of a perennial ryegrass glycine-rich
      RNA-binding protein gene suggest a role in cold adaptation.
AB  - A perennial ryegrass cDNA clone encoding a putative glycine-rich RNA binding
      protein (LpGRP1) was isolated from a cDNA library constructed from crown tissues
      of cold-treated plants. The deduced polypeptide sequence consists of 107 amino
      acids with a single N-terminal RNA recognition motif (RRM) and a single C
      terminal glycine-rich domain. The sequence showed extensive homology to glycine
      rich RNA binding proteins previously identified in other plant species. LpGRP1
      specific genomic DNA sequence was isolated by an inverse PCR amplification. A
      single intron which shows conserved locations in plant genes was detected between
      the sequence motifs encoding RNP-1 and RNP-2 consensus protein domains. A
      significant increase in the mRNA level of LpGRP1 was detected in root, crown and
      leaf tissues during the treatment of plants at 4 degrees C, through which
      freezing tolerance is attained. The increase in the mRNA level was prominent at
      least 2 h after the commencement of the cold treatment, and persisted for at
      least 1 week. Changes in mRNA level induced by cold treatment were more obvious
      than those due to treatments with abscisic acid (ABA) and drought. The LpGRP1
      protein was found to localise in the nucleus in onion epidermal cells, suggesting
      that it may be involved in pre-mRNA processing. The LpGRP1 gene locus was mapped
      to linkage group 2. Possible roles for the LpGRP1 protein in adaptation to cold
      environments are discussed.

PMID- 16614780
TI  - Variations in epilimnion thickness in small boreal shield lakes: relationships
      with transparency, weather and acidification.
AB  - We used multiple linear regression analysis to investigate relationships between
      late-summer epilimnion thickness, transparency, lake area, acidity and summer
      weather conditions in a large ($n = 116$) multi-year data set for 9 small Boreal
      Shield lakes. Dissolved organic carbon (DOC) was the best individual predictor of
      late summer epilimnion thickness ($r;{2} = 0.69$). Total chlorophyll~$a$, the
      number of days between ice-out and late-summer stratification, and lake area
      collectively explained an additional 14% of the variation in epilimnion
      thickness. The three attributes of summer weather that we examined, mean daily
      temperature, mean daily wind speed, and mean daily hours of bright sunshine, did
      not add to the predictive ability of our regression model. Lake acidity also did
      not add directly to the predictive ability of the model, likely because DOC
      concentrations already reflected the effects of pH. Our study supports an
      increasing body of evidence indicating that the dominant effects of climate
      change on lake thermal structure in small lakes will be through effects on
      processes that affect lake transparency.

PMID- 16614781
TI  - Quality of shallow groundwater and drainage water in irrigated agricultural lands
      in a Mediterranean coastal region of Turkey.
AB  - Spatial and seasonal differences in water quality of drainage water and
      unconfined shallow groundwater were related to irrigation in Samandag, a
      Mediterranean coastal region. Eighteen wells, seven drainage points and Orontes
      River were monitored bimonthly for one year for analyses of electrical
      conductivity (EC), total dissolved solids (TDS), sodium adsorption ratio (SAR),
      cations (Na, K, Ca + Mg) and anions (CO(3), HCO(3), Cl and SO(4)). Agricultural
      irrigation using saline groundwater decreased water quality of Orontes River
      during the irrigation season (May to September) more than during the non
      irrigation season (October to April). Seasonal fluctuations in water quality of
      shallow groundwater were greater during the irrigation season than the non
      irrigation season in the study area. Excessive use of groundwater resulted in a
      decline in the water table levels in the irrigation season. Water table level
      rose up to the soil surface in areas where there was a lack of drainage or poor
      drainage, due to the impact of precipitation in the winter. SAR and pH values of
      drainage water increased in the irrigation season, while the other properties of
      drainage water decreased. Irrigation water quality of Orontes River was
      classified as C(3)S(1) in both seasons. Irrigation water quality of shallow
      groundwater and drainage water varied from C(2)S(1) to C(4)S(2) in one year.
      Drainage and well waters were found to be different on yearly basis in terms of
      Na, SAR (p<0.01) and Ca + Mg concentrations (p<0.001). Ca + Mg concentrations for
      both sources were different for all sampling dates (p<0.001).

PMID- 16614777
TI  - Testifying the rice bacterial blight resistance gene xa5 by genetic
      complementation and further analyzing xa5 (Xa5) in comparison with its homolog
      TFIIAgamma1.
AB  - The recessive gene xa5 for resistance to bacterial blight resistance of rice is
      located on chromosome 5, and evidence based on genetic recombination has been
      shown to encode a small subunit of the basal transcription factor IIA (Iyer and
      McCouch in MPMI 17(12):1348-1354, 2004). However, xa5 has not been demonstrated
      by a complementation test. In this study, we introduced the dominant allele Xa5
      into a homozygous xa5-line, which was developed from a cross between IRBB5 (an
      indica variety with xa5) and Nipponbare (a japonica variety with Xa5).
      Transformation of Xa5 and subsequent segregation analysis confirmed that xa5 is a
      V39E substitution variant of the gene for TFIIAgamma on chromosome 5 (TFIIAgamma5
      or Xa5). The rice has an addition gene for TFIIAgamma exists on chromosome 1
      (TFIIAgamma1). Analysis of the expression patterns of Xa5 (TFIIAgamma5)/xa5 and
      TFIIAgamma1 revealed that both the genes are constitutively expressed in
      different rice organs. However, no expression of TFIIAgamma1 could be detected in
      the panicle by reverse transcriptase-polymerase chain reaction. To compare the
      structural difference between the Xa5/xa5 and TFIIAgamma1 proteins, 3-D
      structures were predicted using computer-aided modeling techniques. The modeled
      structures of Xa5 (xa5) and TFIIAgamma1 fit well with the structure of TFIIA
      small subunit from human, suggesting that they may all act as a small subunit of
      TFIIA. The E39V substitution in the xa5 protein occurs in the alpha-helix domain,
      a supposed conservative substitutable site, which should not affect the basal
      transcription function of TFIIAgamma. The structural analysis indicates that xa5
      and Xa5 potentially retain their basic transcription factor function, which, in
      turn, may mediate the novel pathway for bacterial blight resistance and
      susceptibility, respectively.

PMID- 16614782
TI  - Assessment of air quality after the implementation of compressed natural gas
      (CNG) as fuel in public transport in Delhi, India.
AB  - Public transport in Delhi was amended by the Supreme Court of India to use
      Compressed Natural Gas (CNG) instead of diesel or petrol. After the
      implementation of CNG since April 2001, Delhi has the highest fraction of CNG-run
      public vehicles in the world and most of them were introduced within 20 months.
      In the present study, the concentrations of various criteria air pollutants (SPM,
      PM(10), CO, SO(2) and NO(x)) and organic pollutants such as benzene, toluene,
      xylene (BTX) and polycyclic aromatic hydrocarbons (PAHs) were assessed before and
      after the implementation of CNG. A decreasing trend was found for PAHs, SO(2) and
      CO concentrations, while the NO(x) level was increased in comparison to those
      before the implementation of CNG. Further, SPM, PM(10), and BTX concentrations
      showed no significant change after the implementation of CNG. However, the BTX
      concentration demonstrated a clear relation with the benzene content of gasoline.
      In addition to the impact of the introduction of CNG the daily variation in PAHs
      levels was also studied and the PAHs concentrations were observed to be
      relatively high between 10 pm to 6 am, which gives a proof of a relation with the
      limited day entry and movement of heavy vehicles in Delhi.

PMID- 16614783
TI  - Land-cover changes in an urban lake watershed in a mega-city, Central China.
AB  - Urbanization can exert a profound influence on land covers and landscape
      characteristics. In this study, we characterize the impact of urbanization on
      land cover and lacustrine landscape and their consequences in a large urban lake
      watershed, Donghu Lake watershed (the largest urban lake in China), Central
      China, by using Landsat TM satellite images of three periods of 1987, 1993 and
      1999 and ground-based information. We grouped the land covers into six
      categories: water body, vegetable land, forested land, shrub-grass land, open
      area and urban land, and calculated patch-related landscape indices to analyze
      the effects of urbanization on landscape features. We overlaid the land cover
      maps of the three periods to track the land cover change processes. The results
      indicated that urban land continuously expanded from 9.1% of the total watershed
      area in 1987, to 19.4% in 1993, and to 29.6% in 1999. The vegetable land
      increased from 7.0% in 1987, 11.9% in 1993, to 13.9% in 1999 to sustain the
      demands of vegetable for increased urban population. Concurrently, continuous
      reduction of other land cover types occurred between 1987 and 1999: water body
      decreased from 30.4% to 23.8%, and forested land from 33.6% to 24.3%. We found
      that the expansion of urban land has at least in part caused a decrease in
      relatively wild habitats, such as urban forest and lake water area. These
      alterations had resulted in significant negative environmental consequences,
      including decline of lakes, deterioration of water and air quality, and loss of
      biodiversity.

PMID- 16614784
TI  - Assessing water clarity as a component of water quality in Gulf of Mexico
      estuaries.
AB  - The U.S. Environmental Protection Agency Environmental Monitoring and Assessment
      Program (EMAP) uses water clarity as a water quality indicator for integrated
      assessments of coastal waters. After the publication of the first National
      Coastal Condition Report (USEPA, 2001c), the national water clarity reference
      value of 10% of ambient surface light at 1 m depth was reevaluated and modified
      to reflect expected differences in regional reference light conditions. These
      regional differences range from naturally turbid estuaries like those found in
      Mississippi and Louisiana to clear water estuaries expected to support extensive
      beds of submerged aquatic vegetation in, e.g., Florida and Tampa Bays. For the
      second National Coastal Condition Report, water clarity was assessed based on
      regional reference values (USEPA, 2004). Different regional water clarity
      reference values and data collection methods necessitated the development of a
      water clarity index based on light attenuation coefficients (k). This index
      incorporates regional reference conditions and is interchangeable with secchi
      depth and percent light transmission calculated from light meter measurements.
      Evaluation of the water clarity index shows that k values based on transmissivity
      at 1 m can be estimated from secchi depth measurements and successfully used as a
      surrogate for transmissivity calculated from light meter data. An approach for
      assessing water clarity in Gulf of Mexico estuaries using light meter data and
      secchi depth is presented.

PMID- 16614785
TI  - Mental health and the timing of men's retirement.
AB  - BACKGROUND: Analysis of the Psychiatric Morbidity Survey of Great Britain showed
      that the prevalence of common mental disorders was lower amongst men at or above
      Britain's state pension age of 65, relative to younger men. Retirees below this
      age had consistently higher rates of mental disorders than working men. In
      contrast, the low prevalence of mental disorders amongst retirees aged 65 and
      older was similar to that of their working peers. The aim of this analysis was to
      investigate this pattern of results in a national sample of Australian men, and
      the mediating role of socio-demographic factors. METHOD: Data were from the
      Household, Income and Labour Dynamics (HILDA) in Australia survey (2003). The
      analyses included men aged 45-74 years who were active in the labour force (n =
      1309), or retired (n = 635). Mental health was assessed using the mental health
      scale from the Short-Form 36 Health Questionnaire. RESULTS: Retirees were more
      likely to have mental health problems than their working peers, however this
      difference was progressively smaller across age groups. For retirees above,
      though not below, the age of 55 this difference was explained by poorer physical
      functioning. When age at retirement was considered it was found that early
      retirees who were now at or approaching the conventional retirement age did not
      display the substantially elevated rates of mental health problems seen in their
      younger counterparts. Further, men who had retired at age 60 or older did not
      display an initially elevated rate of mental health problems. CONCLUSIONS: The
      association between retirement and mental health varies across older adulthood.
      Retired British and Australian men below the conventional retirement age of 65
      are more likely to have mental health problems relative to their working peers,
      and retirees above this age. However, poor mental health appears to be linked to
      being retired below this age rather than an enduring characteristic of those who
      retire early.

PMID- 16614786
TI  - Children aged 4-8 years treated with parent training and child therapy because of
      conduct problems: generalisation effects to day-care and school settings.
AB  - In this study, generalisation effects to day-care/school settings were examined
      in an outpatient clinic sample of 127 children aged 4-8 years treated because of
      oppositional conduct problems in the home with parent training (PT) and parent
      training combined with child therapy (CT) ("Incredible Years"). Before treatment
      all children scored above the 90th percentile on the Eyberg Child Behavior
      Inventory (ECBI) for home problems, and met criteria for a possible or a
      confirmed diagnosis of either an oppositional defiant (ODD) or a conduct (CD)
      disorder. Further, 83% of the children showed clinical levels of conduct problems
      both at home and in day-care/school before treatment. Although most children
      improved at home, the majority still showed clinical levels of conduct problems
      in day-care/school settings after treatment and 1-year later. Combined PT and CT
      produced the most powerful and significant generalisation effects across the
      treatment period, however these improvements were not maintained 1-year later for
      most areas. The results of the present study, therefore, underline the need to
      target conduct problems not only exhibited at home but also in day-care/school
      settings, and to develop strategies to maintain positive generalisation effects
      after treatment for this age and problem-group.

PMID- 16614787
TI  - Autism and developmental delay: a comparative clinical study in very young
      children using IBSE scale.
AB  - OBJECTIVE: This study improves the knowledge of early autistic symptomatology and
      research concerning (i) the significant differences in the behaviors of children
      with autistic disorder (AD) and children with a developmental delay (DD), and
      (ii) the influence of the cognitive delay on symptomatology. METHOD: Two groups
      of 20 young children (7-42 months) were compared: children with AD, and those
      with DD. The groups were paired by chronological and developmental age. The
      comparison was extended to four subgroups composed according to age (younger and
      older children--<24 months, >24 months) and to the global development quotient
      (GDQ) (the more and less delayed). Each child was evaluated with the Infant
      Behavior Summarized Evaluation scale (IBSE). RESULTS: For the younger AD
      children, significant differences affected social communication and their
      adaptation to the environment (intolerance to frustration, resistance to change).
      For the older children (>24 months), this study showed the rapid progression of
      the number of distinctive signs between AD and DD children according to age
      and/or developmental level. CONCLUSIONS: Cognitive delay has an important
      influence on the symptomatology at the moment of initial recognition of an
      autistic syndrome. This study is a complement for the fuller understanding of the
      nature and early diagnosis of disorders specific to autism at the earliest phases
      of development.

PMID- 16614788
TI  - Emotional and behavioural difficulties in children of parents with multiple
      sclerosis: a controlled study in Greece.
AB  - Emotional and behavioural problems were investigated in children who have a
      parent with multiple sclerosis (MS), in relation to factors such as family
      dysfunction, parental depression and illness-related characteristics. The
      participants were 56 MS patients, their spouses and one randomly selected child
      aged 4-17 years, and a comparison group of 64 children and both their parents,
      none of whom reported somatic illness. Emotional and behavioural problems in the
      children were identified by reporting of both parents and self-report using the
      Achenbach's Child Behaviour Checklist and Youth Self Report respectively.
      Parental depression and family dysfunction were explored using the Beck
      Depression Inventory and Family Assessment Device, respectively. The data were
      analysed using independent samples t-tests for between-group comparisons, Pearson
      r correlations between children's problems and family dysfunction or parental
      depression, and multiple regression analyses for identifying predictors for
      children's problems. Children whose parents, especially mothers, had MS presented
      greater emotional and behavioural problems than comparison children. Children's
      problems were positively associated with maternal depression and family
      dysfunction. Family dysfunction predicted children's overall and externalizing
      problems, while the severity of impairment of the ill mother predicted children's
      internalizing problems. Implications of these findings for clinical practice are
      discussed.

PMID- 16614789
TI  - White matter damage of patients with Alzheimer's disease correlated with the
      decreased cognitive function.
AB  - Increasing evidence demonstrates that there is marked damage and dysfunction in
      the white matter in Alzheimer's disease (AD). The present study investigates the
      nature of white matter damage of patients with Alzheimer's disease with diffusion
      tensor magnetic resonance imaging (DTI) and analyses the relationship between the
      white matter damage and the cognition function. DTI, as well as T1 fluid
      attenuated inversion recovery (FLAIR) and T2-FLAIR, was performed on probable
      patients of Alzheimer's disease, and sex and age matched healthy volunteers to
      measure the fractional anisotropy (FA) and mean diffusivity (MD) in the genu and
      splenium of the corpus callosum, anterior and posterior limbs of the internal
      capsule, and the white matter of frontal, temporal, parietal, and occipital
      lobes. FA was lower in the splenium of corpus callosum, as well as in the white
      matter of the frontal, temporal, and parietal lobes from patients with
      Alzheimer's disease than in the corresponding region from healthy controls and
      was strongly positive correlated with MMSE scores, whereas FA appeared no
      different in the anterior and posterior limbs of internal capsule, occipital
      lobes white matter, and the genu of corpus callosum between the patients and
      healthy controls. MD was significantly higher in the splenium of corpus callosum
      and parietal lobes white matter from patients than in that those from healthy
      controls and was strongly negative correlated with MMSE scores, whereas MD in the
      anterior and posterior limbs of internal capsule, as well as in frontal,
      temporal, occipital lobes white matter and the genu of corpus callosum, was not
      different between the patients and healthy controls. The most prominent
      alteration of FA and MD was in the splenium of corpus callosum. Our results
      suggested that white matter of patients with Alzheimer's disease was selectively
      impaired and the extent of damage had a strong correlation with the cognitive
      function, and that selective impairment reflected the cortico-cortical and
      cortico-subcortical disconnections in the pathomechanism of Alzheimer's disease.
      The values of FA and MD in white matter, especially in the splenium of corpus
      callosum in AD patients, might be a more appropriate surrogate marker for
      monitoring the disease progression.

PMID- 16614790
TI  - Screening for autistic spectrum in children aged 14 to 15 months. I: the
      development of the Early Screening of Autistic Traits Questionnaire (ESAT).
AB  - This article describes the development of a screening instrument for young
      children. Screening items were tested first in a non-selected population of
      children aged 8-20 months (n = 478). Then, parents of children with clinically
      diagnosed ASD (n = 153, average age 87 months) or ADHD (n = 76, average age 112
      months) were asked to score the items retrospectively for when their child was 14
      months old. A 14-item screening instrument, Early Screening of Autistic Traits
      (ESAT) which had maximal sensitivity and specificity for ASD was developed. The
      sensitivity of the ESAT was checked in an independent sample of 34 children aged
      16-48 months clinically diagnosed with ASD. A 4-item version appears to be a
      promising prescreening instrument.

PMID- 16614792
TI  - Combination therapy of prednisolone and mizoribine improves cryoglobulinemic
      vasculitis with purpura and skin ulcers.
AB  - Conventional treatment is not standardized for hepatitis C virus-negative
      cryoglobulinemia, but corticosteroids, immunosuppressive agents, and plasma
      exchange typically improved the symptoms. Mizoribine is an immunosuppressive
      agent that was developed in Japan and has been found to inhibit the proliferation
      of lymphocytes, especially B cells. We have encountered an elder patient who had
      hepatitis C virus-negative, type II cryoglobulinemic vasculitis with leg purpura
      and skin ulcers. Her symptoms improved and cryoglobulin disappeared by the
      combination therapy of prednisolone and mizoribine. We speculate the action
      mechanism of this therapy is due to immunosuppressive effects including up
      regulation of the efficacy of prednisolone by mizoribine.

PMID- 16614791
TI  - Hyperserotoninemia and altered immunity in autism.
AB  - One of the most consistent biological findings in autism is elevated whole blood
      serotonin (5-HT) levels found in about 1/3 of cases. Immune abnormalities are
      also commonly observed in this disorder. Given 5-HT's role as an immunomodulator,
      possible connections between 5-HT and immune abnormalities in autism are explored
      in this review. Areas of focus include hyperserotoninemia and cellular immune
      function, autoantibodies to 5-HT receptors, and 5-HT's role in autoimmunity.
      Further research is needed to determine the interactions between neuropsychiatric
      and immune dysfunction in autism and related disorders.

PMID- 16614793
TI  - Oral cyclophosphamide improves pulmonary function in scleroderma patients with
      fibrosing alveolitis: experience in one centre.
AB  - Lung involvement constitutes nowadays the major cause of morbidity and mortality
      in scleroderma patients. Pulmonary fibrosis in systemic sclerosis (SSc) is
      thought to be the consequence of interstitial inflammation. Early diagnosis and
      treatment of active alveolitis is essential to prevent the deterioration of
      pulmonary function, improving outcome in SSc patients. The aim of the study was
      to investigate the effect of 1-year treatment with oral cyclophosphamide (CYC) on
      the evolution of interstitial lung disease in scleroderma patients with a
      diagnosis of active alveolitis. An open-label one-arm monocenteric study was
      conducted on 33 scleroderma patients with active alveolitis--defined as the
      presence of areas of 'ground-glass attenuation' on high-resolution computed
      tomography and a recent deterioration in lung function-treated with oral CYC 2 mg
      kg-1 day-1 for 1 year and medium-low dose steroids (prednisone 25 mg for 3 months
      and then tapered to 5 mg/day). Results showed that diffusing capacity for carbon
      monoxide (DLco) values remained stable after 6 months of treatment and
      significantly increased after 12 months (2.06+/-1.38, 2.21+/-1.62 and 2.39+/-1.64
      mmol/min/kPa, at baseline/6/12 months, respectively; p<0.001 12th month vs
      baseline) vital capacity (VC) values slightly increased (i.e. stabilised) in the
      same time frame (2.46+/-0.71, 2.41+/-0.76 and 2.56+/-0.75 l). Accordingly, the
      vast majority of our patients (n=29, 87.9%) presented a DLco and/or a VC
      improvement or stabilisation with respect to baseline. Favourable results were
      more likely to be observed in patients with a lower Wells' radiological grade
      (grade I). In 25 patients followed up for further 12 months after the
      interruption of therapy, VC and DLco remained stable. Thus, long-term therapy
      with oral CYC is effective in ameliorating and/or stabilising lung function in
      scleroderma patients with active alveolitis, with beneficial effects lasting up
      to 1 year after interruption. The higher efficacy in those patients with an early
      pulmonary disease stage and a lower radiological grade underlies the importance
      of an early diagnosis and intervention.

PMID- 16614794
TI  - Successful use of cyclosporin A in severe Schonlein-Henoch nephritis resistant to
      both methylprednisolone pulse and azathioprine.
AB  - Schonlein-Henoch nephritis (SHN) usually presents with micro-haematuria or mild
      proteinuria but can be associated with heavy proteinuria and nephrotic or acute
      nephritic syndrome. Although the treatment of SHN is still under debate, it has
      been suggested that cyclosporin A (CsA) may be beneficial in children with severe
      SHN, as reported by Ronkainen et al. (Pediatr Nephrol 18:1138-1142, 2003) and
      Someya et al. (Pediatr Int 46:111-113, 2004). However, histological effects of
      CsA on severe SHN had not been evaluated in their evaluations. We report the
      successful use of CsA in a male patient with severe SHN with nephrotic-range
      proteinuria, who failed to respond to methylprednisolone pulse and azathioprine
      therapy.

PMID- 16614795
TI  - A -16C>T substitution in the 5' UTR of the puratrophin-1 gene is prevalent in
      autosomal dominant cerebellar ataxia in Nagano.
AB  - The molecular bases of autosomal dominant cerebellar ataxia (ADCA) have been
      increasingly elucidated, but 17-50% of ADCA families still remain genetically
      undefined in Japan. In this study we investigated 67 genetically undefined ADCA
      families from the Nagano prefecture, and found that 63 patients from 51 families
      possessed the -16C>T change in the puratrophin-1 gene, which was recently found
      to be pathogenic for 16q22-linked ADCA. Most patients shared a common haplotype
      around the puratrophin-1 gene. All patients with the -16C>T change had pure
      cerebellar ataxia with middle-aged or later onset. Only one patient in a large, 
      16C>T positive family did not have this change, but still shared a narrowed
      haplotype with, and was clinically indistinguishable from, the other affected
      family members. In Nagano, 16q22-linked ADCA appears to be much more prevalent
      than either SCA6 or dentatorubral-pallidoluysian atrophy (DRPLA), and may explain
      the high frequency of spinocerebellar ataxia.

PMID- 16614797
TI  - Chitosan hydrogel as a drug delivery carrier to control angiogenesis.
AB  - An aqueous solution of photocrosslinkable chitosan containing azide groups and
      lactose moieties (Az-CH-LA) incorporating paclitaxel formed an insoluble hydrogel
      within 30 s of ultraviolet light (UV) irradiation. The chitosan hydrogel showed
      strong potential for use as a new tissue adhesive in surgical applications and
      wound dressing. The fibroblast growth factor (FGF)-2 molecules retained in the
      chitosan hydrogel and in an injectable chitosan/IO(4)-heparin hydrogel remain
      biologically active, and were gradually released from the hydrogels as they
      biodegraded in vivo. The controlled release of biologically active FGF-2
      molecules from the hydrogels caused induction of angiogenesis and collateral
      circulation occurred in healing-impaired diabetic (db/db) mice and in the
      ischemic limbs of rats. Paclitaxel, which is an antitumor reagent, was also
      retained in the chitosan hydrogel and remained biologically active as it was
      released on degradation of the hydrogel in vivo. The chitosan hydrogels
      incorporating paclitaxel effectively inhibited tumor growth and angiogenesis in
      mice. The purpose of this review is to describe the effectiveness of chitosan
      hydrogel as a local drug delivery carrier for agents (e.g., FGF-2 and paclitaxel)
      to control angiogenesis. It is thus proposed that chitosan hydrogel may be a
      promising new local carrier for drugs such as FGF-2 and paclitaxel to control
      vascularization.

PMID- 16614799
TI  - Role of ventricular assist devices in the German heart allocation system.
AB  - The Eurotransplant (ET) allocation algorithm, newly implemented in 2000, gives
      priority for heart transplantation (HTx) to patients with high urgency (HU)
      status, but now this status is rescinded upon ventricular assist device (VAD)
      implantation and only regained if severe complications occur during mechanical
      circulatory support (MCS). We studied the effects of this change on the patients
      in our institute who were waiting for HTx with MCS. The median duration of MCS
      until HTx in adult patients gradually increased from 3.1 months in 1994, reaching
      a peak of 16.7 months in 2000, and then gradually decreased to 6.0 months in
      2003. Among the patients with VAD implantation as a bridge to HTx, two patients
      were on MCS for more than 1 year (the longest duration of MCS being 1.6 years) at
      the end of 1999, and this figure increased to nine patients and a maximum MCS
      duration of 3.7 years at the end of 2003. These data imply that the patients in
      whom a complication occurred in the early phase of MCS and who had overcome this
      complication underwent HTx early with HU status, and those who were stable during
      MCS waited a long time for HTx. Furthermore, the number of patients in the latter
      group is increasing. The new allocation algorithm imposes on patients with MCS
      waiting for HTx who are relatively young and free from complications and serious
      coexisting disease, very long-term MCS without an end to VAD bridging, which is
      almost equivalent to destination therapy.

PMID- 16614798
TI  - Artificial liver support at present and in the future.
AB  - Liver failure is a fatal disease. Liver transplantation is the only established
      treatment for liver failure; however, donor shortages remain problematic. In the
      United States and Europe, artificial livers as a bridge to liver transplantation
      are being considered. In Japan, we have taken a different approach to the
      treatment of end-stage liver diseases because of the characteristics of the
      health-care insurance system, regulated by the government. Furthermore, cadaveric
      liver transplantations are unsuited to the social mores of Japanese culture.
      Practically speaking, we believe that plasma exchange (PE) and continuous
      hemodiafiltration (CHDF) are the most effective therapies for the treatment of
      liver failure, although randomized controlled studies are needed to determine
      their effects. Overall, we believe that the first line of treatment for liver
      failure should be PE and CHDF, and the second line should be bioartificial liver
      support. In the near future, we hope that both gene therapy and regenerative
      medicine will contribute to the development of a functional artificial liver.

PMID- 16614800
TI  - Design of an intravenous oxygenator.
AB  - The aim of this study was to design a new intravenous blood-gas exchange device
      and to estimate the design characteristics of the device with a dimensionless
      function by using a substance that can be used instead of bovine blood. In
      addition, the characteristics of oxygen transfer were estimated using empirical
      formulas and the reliability of the equations was ascertained by comparing their
      output with an experiment performed using bovine blood. The dimensionless
      function was derived using distilled water and bovine blood to estimate the
      oxygen transfer rate. Using the derived equations, the calculated oxygen transfer
      rates for bovine blood and distilled water were similar for Reynolds numbers
      ranging from 0.7 to 7.0. Therefore, it is possible to estimate the oxygen
      transfer rate in bovine blood, which is a non-Newtonian fluid, using distilled
      water, which is a Newtonian fluid. Moreover, it was possible to verify the
      related equations because the oxygen transfer rate could be estimated using the
      derived equations, according to the diameters of the various device modules.

PMID- 16614801
TI  - Bileaflet mechanical valve sound analysis using a continuous wavelet transform.
AB  - Bileaflet mechanical valve closing sounds have splits, the duration of which is
      not constant in normally functioning valves. However, no reports have discussed
      the influences of valve malfunction on the split interval, neither have any
      studies discussed the fact that mechanical valve closing sound signals must be
      analyzed using a time-frequency analysis because they are nonstationary signals.
      The continuous wavelet transform (CWT), a time-frequency analyzing method using
      mother wavelets modified by scale numbers, was selected in this study for
      analyzing bileaflet valve closing sounds because it is easy to understand and has
      no limitations such as the cross-terms in the Wigner-Ville distribution or the
      tradeoff between time and frequency resolutions of the short-time Fourier
      transform. This study compares the properties of the mother wavelets of various
      CWTs and selects one that is suitable for detection of the clear split in
      bileaflet mechanical valve closing sound signals. This article also establishes a
      standard frequency analyzing system for bileaflet mechanical valve sounds. A
      preliminary study with chirp Doppler signals for comparing the frequency
      properties of the mother wavelets of various CWTs suggested that Ishikawa's
      modified Morlet CWT has better time and frequency resolution at the highest
      frequency scale. Morlet/power CWT analysis of normal in vivo bileaflet valve
      closing sounds of the ST. Jude Medical (SJM), ATS, and Carbomedics (CM) valves
      demonstrated clear splits of very short interval at the highest level of
      frequency. Detection of the disappearance of the split by using this analytical
      method may be the key to identifying bileaflet mechanical valve malfunction in
      outpatient departments.

PMID- 16614802
TI  - Development of vitamin E-modified polysulfone membrane dialyzers.
AB  - Oxygen radicals have recently been attracting close attention because of their
      involvement in tissue damage and their close relationship to various clinical
      conditions. It has been suggested that hemodialysis increases oxidative stress,
      triggering the development of complications such as atherosclerosis and dialysis
      related amyloidosis. We recently developed a dialyzer containing a highly
      functional polysulfone membrane on which vitamin E had been bonded (PS-ViE). The
      present study was undertaken to evaluate the biocompatibility of this membrane
      and to conduct other experiments on the membrane in vitro. Human blood was
      dialyzed with minidialyzers (300-600 cm(2) membrane area) made of PS-ViE,
      cellulose, or untreated polusulfone (PS), and the effects of the dialyzers on
      complements (C3a, C4a, and C5a), cytokines (IL-1beta and IL-8), and granulocyte
      elastase as well as their anti-oxidative activity were investigated (n = 6). The
      effect of PS-ViE on complement activation and its effects on cytokines were
      comparable to those of PS membrane, whereas granulocyte elastase following
      dialysis with the PS-ViE membrane tended to be lower than that seen with PS
      membrane. The effects of PS-ViE-induced methemoglobin, lipid peroxide, and oxygen
      radicals were significantly less than those of PS membrane, indicating the
      antioxidative activity of PS-ViE. Vitamin E-modified polysulfone membrane
      dialyzers were found to have favorable effects on the immune system and to
      express antithrombotic and antioxidative effects.

PMID- 16614803
TI  - Corrosion of stainless steel sternal wire after long-term implantation.
AB  - A variety of metallic components have been used in medical devices where lifelong
      durability and physical strength are demanded. To investigate the in vivo changes
      of implanted metallic medical devices in humans, stainless steel sternal wires
      removed from patients were evaluated. Stainless steel (316L) sternal wires
      removed from four patients after 10, 13, 22, and 30 years of implantation were
      evaluated using scanning electron microscopy (SEM) and energy dispersive X-ray
      spectroscopy (EDS). Macroscopically, the removed specimens maintained their
      metallic luster and color. Under SEM, small holes were observed sporadically at
      10 years and they tended to connect in the drawing direction. The longer the
      implanted duration, the more numerous and deeper were the crevices observed. By
      EDS, sulfur, phosphorus, and calcium were identified in all areas at 10 years, in
      addition to the component elements of stainless steel, comprising iron, chromium,
      nickel, and manganese. Corrosion products observed at 30 years were identified as
      calcium phosphate. In conclusion, stainless steel sternal wires develop corroded
      pores that grow larger and deeper with time after implantation; however, the
      pores remain shallow even after decades of implantation and they may not be a
      cause of mechanical failure. An amount of metal ions equivalent to the corroded
      volume must have been released into the human body, but the effect of these metal
      ions on the body is not apparent.

PMID- 16614804
TI  - Idiopathic hypertrophic cranial pachymeningitis successfully treated with weekly
      subcutaneous methotrexate.
AB  - Idiopathic hypertrophic cranial pachymeningitis is a very infrequent disorder.
      Adequate management is still a matter of debate. We describe the use of low-dose
      pulse methotrexate in treating a 63-year-old woman with idiopathic hypertrophic
      cranial pachymeningitis. A weekly scheme with subcutaneous methotrexate was
      tried. Clinical improvement occurred in one week. Total remission of the clinical
      and neuro-imaging abnormalities was evident 6 months later, with minimal side
      effects. The patient is in complete remission after one year of follow-up without
      treatment. Hence, low-dose weekly subcutaneous methotrexate may be safe and
      effective in inducing complete and sustained remission of this condition. The
      experience with subcutaneous methotrexate to treat this entity has never been
      reported.

PMID- 16614805
TI  - Multiparametric analysis of cerebral substrates and nitric oxide delivery in
      cerebrospinal fluid in patients with intracerebral haemorrhage: correlation with
      hemodynamics and outcome.
AB  - BACKGROUND: There is no information regarding the possible role of cerebral
      substrates in the pathogenesis of neuronal injury in intracerebral haemorrhages
      (ICHs). Purposes of this prospective study were to clarify whether changes in
      substrates are the consequence of the initial brain damage in ICH and to
      elucidate the relationship among the biochemical mechanisms and clinical course
      of patients with ICH. METHOD: During a period of two years, patients (GCS < or
      =8) who had ICH secondary to an aneurysm (SAH), stroke (sICH), or trauma (tICH)
      and underwent ventriculostomy with ICP monitoring and/or underwent cranial
      surgery were randomly enrolled in this study. Extracellular concentrations of
      glutamate, aspartate, glycine, GABA, lactate, lactate/pyruvate ratio, and glucose
      in the CSF were measured by use of high-performance liquid chromatography (HPLC).
      The nitric oxide (NO) concentration in the CSF was analyzed by chemiluminescence.
      FINDINGS: There were 75 patients (38 women and 37 men) with ICH included in this
      study. Twenty-one patients had SAH, 28 sICH, and 26 tICH. In tICH patients, there
      was a 30-fold increase in glutamate and a 10-fold in aspartate over reference
      values. The levels of glutamate, aspirate, GABA, lactate, glucose, and NO
      differed significantly among the three groups (p<0.001). There were no
      significant differences in glycine and L/P ratio among the groups. The initial
      GCS, the mean CPP and outcome six months after the insult were all significantly
      correlated with the concentration of substrates (p<0.01), both within groups and
      among the total sample. The CSF levels of glutamate lactate, NO and glucose
      correlated significantly with outcome (p<0.005). CONCLUSIONS: This study confirms
      the correlation between the level of EAAs and the outcome of ICHs, suggesting
      that neurochemical monitoring of these substances may have a role in caring for
      patients.

PMID- 16614806
TI  - Measurement of adhesion energies and Young's modulus in thin polymer films using
      a novel axi-symmetric peel test geometry.
AB  - We present a novel method of probing adhesion energies of solids, particularly
      polymers. This method uses the axi-symmetric deformation of a thin spincast
      polymer membrane brought into contact with a flat substrate to probe the work of
      adhesion. The use of a thin membrane minimizes uncertainty in the radius of
      contact, while the use of spincast films provides very smooth surfaces by means
      of a very simple method. The experimental profile of the deformed membrane shows
      good agreement with the expected logarithmic profile. The experimental setup
      enables the measurement of Young's modulus and the solid-solid work of adhesion
      for thin films. The value obtained for Young's modulus of polystyrene (PS) was
      found to be in agreement with other conventional measurement techniques. In
      addition, measurement of the work of adhesion at the PS/silicon oxide interface
      was possible. The apparatus is well suited to studying the dependence of Young's
      modulus, work of adhesion and fracture energy on membrane thickness, temperature,
      pulling rate, and ageing of the interface, and can readily be modified to study
      biologically relevant samples.

PMID- 16614807
TI  - Bronchoalveolar levels of plasminogen activator inhibitor-1 and soluble tissue
      factor are sensitive and specific markers of pulmonary inflammation.

PMID- 16614808
TI  - Isoflurane therapy for severe refractory status asthmaticus in children.
AB  - OBJECTIVE: To describe the use of inhaled isoflurane in a series of children with
      life-threatening asthma. DESIGN: Retrospective case series. SETTING: Pediatric
      intensive care unit of a tertiary-care children's hospital. Ten children ranging
      in age from 1 to 16 years with 11 episodes of severe asthma requiring invasive
      mechanical ventilation in the pediatric intensive care unit over a 5-year period.
      RESULTS: Isoflurane resulted in an improvement in arterial pH and a reduction in
      partial pressure of arterial carbon dioxide (PaCO(2)) in all the 11 instances.
      This effect was sustained in 10 cases and led to clinical improvement and rapid
      weaning from mechanical ventilation. One child failed to show sustained response
      and was placed on veno-venous extracorporeal membrane oxygenation. One child died
      secondary to anoxic brain injury sustained prior to hospitalization. Hypotension
      was the major side effect, and occurred in 8 children necessitating vasopressor
      support. CONCLUSIONS: Isoflurane improves arterial pH and reduces partial
      pressure of arterial carbon dioxide in mechanically ventilated children with life
      threatening status asthmaticus who are not responsive to conventional management.

PMID- 16614809
TI  - Ethical, political, and social aspects of high-technology medicine: Eos and care.
AB  - OBJECTIVE: We discuss biosocial aspects of high-technology medicine (HTM) to
      provide a global view of the current model of medicine in the developed world and
      its consequences. METHODS: We analyze changes in the concept of death and in the
      use and cost of HTM. The consequences of HTM on the delivery of basic medical
      care within and among countries are discussed. Concepts derived from Greek
      mythology are used to illustrate the problems associated with HTM. RESULTS: HTM
      can be extremely effective in individual cases, but it poses important bioethical
      and biosocial problems. A major problem is related to the possibility of
      manipulating the process of dying and the consequent alteration in the social
      concept of death, which, if not carefully regulated, risks transforming medicine
      into an expensive way of pursuing pointless dreams of immortality (myth of Eos).
      Another problem is related to the extraordinary amount of resources necessary for
      HTM. This model of medicine (which is practiced daily) has limited
      sustainability, can work only in highly developed countries, may contribute to
      unequal access to health care, and has negligible positive impact on global
      health and survival. CONCLUSIONS: HTM poses very important biosocial questions
      that need to be addressed in a wider and transparent debate, in the best interest
      of society and HTM as well.

PMID- 16614810
TI  - Transnasal puncture based on echographic sinusitis evidence in mechanically
      ventilated patients with suspicion of nosocomial maxillary sinusitis.
AB  - OBJECTIVE: The aim of this prospective study was to evaluate the value of sinus
      echography results to directly indicate a transnasal puncture in intubated
      patients with suspicion of nosocomial maxillary sinusitis. DESIGN: prospective
      clinical investigation. SETTING: medical intensive care unit. PATIENTS: sixty
      patients undergoing intubation and mechanical ventilation more than 2 days, with
      a clinical suspicion of maxillary sinusitis with purulent nasal discharge.
      INTERVENTIONS: 120 sinuses were examined by sinus ultrasound. The image defined
      as normal was an acoustic shadow arising from the front wall. Two levels of
      positive echography were described: (1) a partial sinusogram was defined as the
      visualization of the hyperechogenic posterior wall of the sinus; and (2) a
      complete sinusogram was defined as the hyperechogenic visualization of posterior
      wall and the extension by the internal and external walls of the sinus. When
      sinus ultrasound was positive, a transnasal puncture was performed the same day.
      The transnasal puncture was positive if a fluid was obtained from sinus
      aspiration. The transnasal puncture was negative if there was no aspirated
      material. MEASUREMENTS AND RESULTS: sinus ultrasound was positive in 84 cases (54
      complete sinusograms and 30 partial sinusograms). Seventy-eight of 84 transnasal
      punctures were positive. Sensitivity of a sinusogram for obtaining positive
      transnasal puncture was 100%, and specificity was 86% (100% in case of complete
      sinusogram) in a clinically selected population. The only six negative transnasal
      punctures were performed in patients with partial sinusogram. CONCLUSIONS:
      Ultrasound sinusitis evidence seems to be of value to indicate and perform a
      transnasal puncture directly, avoiding CT exam.

PMID- 16614811
TI  - Prevalence of pulmonary hypertension associated with severe acute respiratory
      distress syndrome: predictive value of computed tomography.
AB  - OBJECTIVE: To evaluate the prevalence of pulmonary hypertension associated with
      severe acute respiratory distress syndrome (ARDS) and to asses the value of
      pulmonary artery trunk diameter (PAT) to predict pulmonary hypertension. DESIGN:
      Prospective study SETTING: University teaching hospital and ARDS referral center.
      PATIENTS: 103 patients with ARDS, who received both right heart catheterization
      and chest computed tomography. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: 95
      patients (92.2%) with ARDS had pulmonary artery hypertension, 16 of them (16.8%)
      mild, 72 (75.8%) moderate, and 7 (7.4%) severe, as assessed by right heart
      catheterization. Of the patients with moderate and severe pulmonary hypertension,
      43 had a pulmonary artery trunk diameter >or=29 mm yielding a sensitivity of 0.54
      and a specificity of 0.63. Pulmonary artery trunk diameter correlated
      significantly but weakly with mean pulmonary artery pressure (r=0.34, p=0.0004).
      The positive predictive value was 0.83, and the negative predictive value was
      0.28. The diagnosis of pulmonary hypertension by PAT diameter measurements was
      incorrect in 43.7% of patients with ARDS. CONCLUSIONS: Pulmonary artery
      hypertension has a high prevalence in patients with severe ARDS. Measurement of
      PAT diameter on admission CT scan is an unreliable tool for identification of
      ARDS patients with pulmonary hypertension.

PMID- 16614813
TI  - Transcript levels in plant mitochondria show a tight homeostasis during day and
      night.
AB  - In plants the physiological and biochemical demands on each cell vary greatly
      between day and night, mostly due to the differing output of photosynthesis.
      Chloroplasts, the organelles of photosynthesis, are biochemically closely linked
      to the other energy generating organelles, the mitochondria. We have now
      investigated whether gene expression in plant mitochondria is influenced by these
      daily physiological variations. Transcript synthesis in these organelles cycles
      in a diurnal rhythm, while steady state transcript levels do not vary between
      light and dark phases and are stable throughout the diurnal (as well as the
      circadian) time course. This finding suggests that available steady state
      transcript levels in plant mitochondria are sufficient to provide the required
      biochemical capacities also at times of peak respiratory and physiological
      demands.

PMID- 16614812
TI  - IBZM tool: a fully automated expert system for the evaluation of IBZM SPECT
      studies.
AB  - PURPOSE: Visual reading of [(123)I]IBZM SPECT scans depends on the experience of
      the interpreter. Therefore, semi-quantification of striatal IBZM uptake is
      commonly considered mandatory. However, semi-quantification is time consuming and
      prone to error, particularly if the volumes of interest (VOIs) are positioned
      manually. Therefore, the present paper proposes a new software tool ("IBZM tool")
      for fully automated and standardised processing, evaluation and documentation of
      [(123)I]IBZM SPECT scans. METHODS: The IBZM tool is an easy-to-use SPM toolbox.
      It includes automated procedures for realignment and summation of multiple frames
      (motion correction), stereotactic normalisation, scaling, VOI analysis of
      striatum-to-reference ratio R, classification of R and standardised display. In
      order to evaluate the tool, which was developed at the University of Hamburg, the
      tool was transferred to the University of Hannover. There it was applied to 27
      well-documented subjects: eight patients with multi-system atrophy (MSA), 12
      patients with Parkinson's disease (PD) and seven controls. The IBZM tool was
      compared with manual VOI analysis. RESULTS: The sensitivity and specificity of
      the IBZM tool for the differentiation of the MSA subjects from the controls were
      100% and 86%, respectively. The IBZM tool provided improved statistical power
      compared with manual VOI analysis. CONCLUSION: The IBZM tool is an expert system
      for the detection of reduced striatal D(2) availability on [(123)I]IBZM SPECT
      scans. The standardised documentation supports visual and semi-quantitative
      evaluation, and it is useful for presenting the findings to the referring
      physician. The IBZM tool has the potential for widespread use, since it appears
      to be fairly independent of the performance characteristics of the particular
      SPECT system used. The tool is available free of charge.

PMID- 16614814
TI  - Chromosomal and phylogenetic context for conglutin genes in Arachis based on
      genomic sequence.
AB  - Comparative genomic and cDNA sequence analysis of ara h 2, a major peanut
      allergen, and a related conglutin ara h 6 were performed in Arachis hypogaea L.
      and its putative progenitors, Arachis duranensis and Arachis ipaensis. The
      complete identity between sequences encoding Ara h 2 isoforms demonstrated that
      these are homeologous genes and represent orthologs from diploid ancestors. Three
      copies of ara h 6 were identified in A. hypogaea, one of them located in the A
      genome and the other two in the B-genome. Expression analysis showed higher
      levels of ara h 2 transcripts compared with ara h 6. Dual-labeled genomic in situ
      hybridization permitted identification of two subgenomes, each of which contained
      one pair of ara h 2-ara h 6 signals localized by fluorescence in situ
      hybridization. Characterization of genomic clones showed close genetic linkage
      between Ara h 2.02 and one copy of ara h 6 in the B-genome. The physical linkage
      may have arisen by tandem duplication and divergence of an ancestral gene. A gene
      duplication event specific to the B-genome progenitor has resulted in ara h 6
      paralogs. These data provide further evidence for progenitor relationships and
      genomic organization of the conglutin gene family in the genus Arachis and could
      contribute to the development of a hypoallergenic peanut.

PMID- 16614816
TI  - Arbuscular mycorrhiza reduces susceptibility of tomato to Alternaria solani.
AB  - Mycorrhiza frequently leads to the control of root pathogens, but appears to have
      the opposite effect on leaf pathogens. In this study, we studied mycorrhizal
      effects on the development of early blight in tomato (Solanum lycopersicum)
      caused by the necrotrophic fungus Alternaria solani. Alternaria-induced necrosis
      and chlorosis of all leaves were studied in mycorrhizal and non-mycorrhizal
      plants over time course and at different soil P levels. Mycorrhizal tomato plants
      had significantly less A. solani symptoms than non-mycorrhizal plants, but
      neither plant growth nor phosphate uptake was enhanced by mycorrhizas. An
      increased P supply had no effect on disease severity in non-mycorrhizal plants,
      but led to a higher disease severity in mycorrhizal plants. This was parallel to
      a P-supply-induced reduction in mycorrhiza formation. The protective effect of
      mycorrhizas towards development of A. solani has some parallels to induced
      systemic resistance, mediated by rhizobacteria: both biocontrol agents are root
      associated organisms and both are effective against necrotrophic pathogens. The
      possible mechanisms involved are discussed.

PMID- 16614815
TI  - Lymphoid tyrosine phosphatase (LYP/PTPN22) Arg620Trp variant regulates insulin
      autoimmunity and progression to type 1 diabetes.
AB  - AIMS/HYPOTHESIS: We analysed the contribution of the lymphoid protein tyrosine
      phosphatase (LYP) Arg620Trp variant (which corresponds to the PTPN22 C1858T
      polymorphism) to the emergence of beta-cell-specific humoral autoimmunity and
      progression to type 1 diabetes in man. We also explored the heterogeneity in the
      disease-predisposing effect of this polymorphism in relation to known disease
      loci, sex and age at disease onset. SUBJECTS AND METHODS: A population-derived
      Finnish birth cohort with increased disease susceptibility conferred by HLA-DQB1
      was monitored for the appearance of islet cell autoantibodies, and individuals
      found to be positive were tested for autoantibodies against insulin (IAA),
      glutamic acid decarboxylase and islet antigen-2 (n = 574; mean follow-up time 4.9
      years). Gene interaction effects on disease susceptibility were analysed in case
      control and family series (546 patients, 538 controls, 245 nuclear families). All
      subjects were typed for HLA DR-DQ, insulin gene (INS), CTLA4 and PTPN22 C1858T
      polymorphisms. RESULTS: The PTPN22 1858TT genotype was associated with the
      appearance of IAA (adjusted hazard ratio = 4.6, 95% CI 2.4-9.0; p = 0.000013).
      PTPN22, INS and HLA-DRB1 had an additive effect on the emergence of IAA. The
      1858TT and CT genotypes conferred an increased risk of developing additional
      autoantibodies or clinical disease (hazard ratio=4.1, 95% CI 1.5-11.6; and 1.6,
      95% CI 1.1-2.4, respectively; p = 0.003). The strong effect of PTPN22 on disease
      susceptibility (p = 2.1 x 10(-8)) was more pronounced in males (p = 0.021) and in
      subjects with non-DR4-DQ8/low-risk HLA genotypes (p = 0.0004).
      CONCLUSIONS/INTERPRETATION: In the pathogenesis of type 1 diabetes the underlying
      mechanism of the PTPN22 C1858T polymorphism appears to involve regulation of
      insulin-specific autoimmunity. Importantly, it strongly affects progression from
      prediabetes to clinical disease.

PMID- 16614817
TI  - Associations between arbuscular mycorrhizal fungi and grasses in the successional
      context of a two-phase mosaic in the Chihuahuan Desert.
AB  - The hypothesis that plant species are more responsive to mycorrhiza in late than
      in early successional stages was assessed in grasses from a successional process
      occurring in two-phase mosaics from the Mexican Chihuahuan Desert. We estimated
      the density of spores of arbuscular mycorrhizal (AM) fungi and the AM
      colonization of pioneer and late-successional grasses in the field. In growth
      chamber experiments, we tested the effect of the native AM fungal community on
      grasses growing in soils from different successional stages. Spore density was
      higher in late than in early successional stages. Late-successional species were
      more responsive to AM (positive AM responsiveness) whereas pioneer species were
      nondependent on mycorrhiza or if associated to AM fungi, the interaction showed a
      negative AM responsiveness for the seedling stage. Our findings showed that late
      successional species fitted the proposed models of mycorrhizal performance, but
      the two pioneer species differed in their AM condition and responsiveness. This
      further supports the idea that AM interactions are more complex along the
      successional processes than the predictions of the more widely cited hypotheses.

PMID- 16614818
TI  - Characterization of LF9, an octoploid strawberry genotype selected for rapid
      regeneration and transformation.
AB  - Cultivated strawberry (Fragaria xananassa) is a valuable crop, yet the absence of
      a rapid, high-throughput transgenic system has precluded meaningful application
      of biotechnology and translation of information from plant models to this crop. A
      new octoploid strawberry genetic line Laboratory Festival #9 has been identified,
      selected solely for its rapid regeneration and efficient transformation. Direct
      organogenesis has been achieved from all tissues tested, with rapidly-growing
      shoot initials visible in as few as 13 days. The conditions for optimal shoot
      regeneration, transformant selection, root generation, and plant acclimatization
      are presented. The progression from explant to plant in soil can be achieved in
      about 60 days. The development of transformation protocols in this rapid-cycling
      genotype allows high-throughput studies of gene function in the octoploid
      strawberry genetic background.

PMID- 16614819
TI  - Comparative analysis of induction pattern of programmed cell death and defense
      related responses during hypersensitive cell death and development of bacterial
      necrotic leaf spots in eggplant.
AB  - Pseudomonas cichorii causes necrotic leaf spots (NLS), while Pseudomonas syringae
      pv. tabaci induces a hypersensitive response (HR) in eggplant. P. cichorii
      induced cell death at 9 h after inoculation (HAI), reaching a maximum of around
      24-30 HAI. On the other hand, cell death was induced 6 HAI with P. syringae pv.
      tabaci, reaching a maximum of around 12-18 HAI. Superoxide generation was
      observed in eggplant inoculated with both bacteria. DNA fragmentation, cytochrome
      c release into the cytosol and expression of defense-related genes such as PR-1
      and hsr203J was also induced by inoculation with both bacteria, but these plant
      reactions were more rapidly induced in eggplant inoculated with P. syringae pv.
      tabaci rather than those with P. cichorii. Lipid peroxidation and induction of
      lipoxygenase (LOX) was drastically induced in eggplant inoculated with P.
      syringae pv. tabaci compared to P. cichorii-inoculated eggplant. Pharmacological
      studies showed that induction of the cell death, and the NLS or the HR in
      response to both bacteria was commonly associated with de novo protein synthesis,
      reactive oxygen species and caspase III-like protease. Interestingly, involvement
      of lipid peroxidation, LOX, serine protease, and DNase differed between induction
      of NLS and HR. These results suggest that programmed cell death might be closely
      associated not only with the HR but also NLS. However, there may be differences
      not only in the induction kinetics and level of plant responses but also in the
      infection-related responses between HR and NLS.

PMID- 16614821
TI  - Modi: a new mobile instrument for in situ double-pulse LIBS analysis.
AB  - Laser-induced breakdown spectroscopy (LIBS) is a promising technique for in situ
      elemental analysis. A new mobile instrument for LIBS analysis, developed in a
      collaboration between Marwan Technology s.r.l. and the Applied Laser Spectroscopy
      Laboratory in Pisa, is presented, and some applications of it and results from it
      are outlined. The innovative experimental set-up, based on the use of two
      suitably retarded laser pulses and a standardless analysis procedure, which
      overcomes problems related to matrix effects, greatly improves the potential of
      this technique for accurate quantitative analysis.

PMID- 16614820
TI  - Functional and phylogenetic analysis of a DREB/CBF-like gene in perennial
      ryegrass (Lolium perenne L.).
AB  - The dehydration-responsive element binding proteins (DREB1)/C-repeat (CRT)
      binding factors (CBF) function as transcription factors and bind to the DRE/CRT
      cis-acting element (core motif: G/ACCGAC) commonly present in cold-regulated
      (COR) genes and subsequently upregulate the expression of such genes in
      Arabidopsis. We identified a DREB1A/CBF3-like gene, designated LpCBF3, from
      perennial ryegrass (Lolium perenne L.) by using RT-PCR and RACE (rapid
      amplification of cDNA end). The LpCBF3 gene contains all the conserved domains
      known to exist in other CBF genes. A comprehensive phylogenetic analysis using
      known and computationally identified CBF homologs in this study revealed that all
      monocot CBF genes are separately clustered from eudicot CBF genes and the LpCBF3
      is the ortholog of rice OsDREB1A/CBF3 gene. Similar to other DREB1A/CBF3
      homologs, expression of the LpCBF3 is induced by cold stress, but not by abscisic
      acid (ABA), drought, or salinity. Overexpression of the LpCBF3 cDNA in
      Arabidopsis induced expression of the Arabidopsis DREB1A/CBF3 target COR genes,
      COR15a and RD29A, without cold acclimation. Ion leakage in leaves of the
      overexpression transgenic plants was significantly reduced, an indication of
      enhanced freezing tolerance. Our data demonstrated that LpCBF3 not only resembles
      DREB/CBF genes of Arabidopsis, but is also capable of functioning as a
      transcriptional regulator in Arabidopsis, a species distant to the grass family.

PMID- 16614822
TI  - Actinomycotic brain infection: registered diffusion, perfusion MR imaging and MR
      spectroscopy.
AB  - INTRODUCTION: Actinomycotic brain infection is caused by an organism of the
      Actinomyces genus. We report here one such case. METHODS: The methods used
      included coregistered diffusion, perfusion and spectroscopic magnetic resonance
      (MR) imaging. RESULTS: Decreased apparent diffusion coefficient, markedly
      elevated fractional anisotropy (FA) and reduced cerebral blood flow were
      observed. MR spectroscopy demonstrated elevated amino acids, acetate and
      succinate. CONCLUSION: Elevated FA values may be due to the microstructure of
      this special brain infection.

PMID- 16614823
TI  - The relationship between stem subsidence and improvement in the radiolucency in
      polished tapered stems.
AB  - We studied the relationship between stem subsidence and improvement in the
      initial radiolucency at the bone-cement interface in polished- and rough-surface
      stems. Stem subsidence was seen in 34 of 42 hips (81.0%), and improvement in the
      initial radiolucency was seen in 15 hips (35.7%) in collarless polished tapered
      stems at 1 year after operation. In polished stems, stem subsidence in cases with
      improvement in the initial radiolucency was significantly greater than in those
      with no change (average 1.12 mm and 0.48 mm, P<0.005). In rough-surface stems
      partially coated with polymethylmethacrylate (VerSys Cemented Plus), no stem
      subsidence and no improvement in the initial radiolucency was seen. In polished
      stems, stem subsidence leads to cement creep and compressive force on the bone
      cement interface and can improve the initial radiolucency.

PMID- 16614824
TI  - Neurotoxicity of the pentabrominated diphenyl ether mixture, DE-71, and
      hexabromocyclododecane (HBCD) in rat cerebellar granule cells in vitro.
AB  - Polybrominated diphenyl ethers (PBDE) and hexabromocyclododecane (HBCD) are
      compounds used as additive flame retardants in plastics, electronic equipment,
      and textiles. The aim of the present study was to investigate the in vitro
      effects of the pentabrominated diphenyl ether mixture, DE-71, and HBCD on
      cerebellar granule cells (CGC). Both DE-71 and HBCD induced death of CGC in low
      micromolar concentrations. The NMDA receptor antagonist MK801 (3 microM), and the
      antioxidant alpha-tocopherol (50 microM) significantly reduced the cell death.
      Incubation of the compounds together with the rat liver post-mitochondrial (S9)
      fraction reduced cell death by 58 and 64% for DE-71 and HBCD, respectively. No
      ROS formation and no elevation in intracellular calcium were observed. We further
      demonstrated apoptotic morphology (Hoechst straining) after exposure to low
      levels of the two brominated flame retardants and signs of DNA laddering were
      found after DE-71 exposure. However, other hallmarks of apoptosis, like caspase
      activity, were absent indicating an atypical form of apoptosis induced by DE-71.
      After intraperitoneal injection of the two compounds both DE-71 and HBCD were
      found in significant amounts in brain (559 +/- 194 and 49 +/- 13 microg/kg,
      respectively) and liver (4,010 +/- 2,437 and 1,248 +/- 505 microg/kg,
      respectively) 72 h after injection. Our results indicate that the lower
      brominated PBDEs have a higher potency of bioaccumulation than HBCD, and that
      both compounds have a neurotoxic potential in vitro.

PMID- 16614825
TI  - Evaluation of the use of salivary lead levels as a surrogate of blood lead or
      plasma lead levels in lead exposed subjects.
AB  - We conducted a study to evaluate the use of parotid salivary lead (Pb-saliva)
      levels as a surrogate of the blood lead (Pb-B) or plasma lead levels (Pb-P) to
      diagnose lead exposure. The relationship between these biomarkers was assessed in
      a lead exposed population. Pb-saliva and Pb-P were determined by inductively
      coupled plasma mass spectrometry, while in whole blood lead was determined by
      graphite furnace atomic absorption spectrometry. We studied 88 adults (31 men and
      57 women) from 18 to 60 years old. Pb-saliva levels varied from 0.05 to 4.4
      microg/l, with a mean of 0.85 microg/l. Blood lead levels varied from 32.0 to
      428.0 microg/l in men (mean 112.3 microg/l) and from 25.0 to 263.0 microg/l (mean
      63.5 microg/l) in women. Corresponding Pb-Ps were 0.02-2.50 microg/l (mean 0.77
      microg/l) and 0.03-1.6 microg/l (mean 0.42 microg/l) in men and women,
      respectively. A weak correlation was found between Log Pb-saliva and Log Pb-B
      (r=0.277, P<0.008), and between Log Pb-saliva and Log Pb-P (r=0.280, P=0.006).
      The Pb-saliva/Pb-P ratio ranged from 0.20 to 18.0. Age or gender does not affect
      Pb-saliva levels or Pb-saliva/Pb-P ratio. Taken together, these results suggest
      that salivary lead may not be used as a biomarker to diagnose lead exposure nor
      as a surrogate of plasma lead levels at least for low to moderately lead exposed
      population.

PMID- 16614826
TI  - On-line optimization of glutamate production based on balanced metabolic control
      by RQ.
AB  - In glutamate fermentations by Corynebacterium glutamicum, higher glutamate
      concentration could be achieved by constantly controlling dissolved oxygen
      concentration (DO) at a lower level; however, by-product lactate also severely
      accumulated. The results of analyzing activities changes of the two key enzymes,
      glutamate and lactate dehydrogenases involved with the fermentation, and the
      entire metabolic network flux analysis showed that the lactate overproduction was
      because the metabolic flux in TCA cycle was too low to balance the glucose
      glycolysis rate. As a result, the respiratory quotient (RQ) adaptive control
      based "balanced metabolic control" (BMC) strategy was proposed and used to
      regulate the TCA metabolic flux rate at an appropriate level to achieve the
      metabolic balance among glycolysis, glutamate synthesis, and TCA metabolic flux.
      Compared with the best results of various DO constant controls, the BMC strategy
      increased the maximal glutamate concentration by about 15% and almost completely
      repressed the lactate accumulation with competitively high glutamate
      productivity.

PMID- 16614827
TI  - Genetic variation within Taenia multiceps in Sardinia, Western Mediterranean
      (Italy).
AB  - Investigations were undertaken on Taenia multiceps to determine if genetic
      variation was present within the parasites of Sardinia (Italy). Forty samples
      were obtained from various locations of Sardinia and deoxyribonucleic acid (DNA)
      was extracted. Polymerase chain reaction (PCR) was performed on NADH
      dehydrogenase I (ND1) and cytochrome c subunit 1 (CO1) mitochondrial genes and
      amplicons were then sequenced and aligned with Bioedit software. Pairwise
      comparison between the ND1 sequences of the T. multiceps isolates showed
      differences ranging from 1.27 to 2.54% using an isolate obtained from Wales as an
      outgroup, while COI sequences showed within the samples coming from Sardinia a
      lesser degree of variability, ranging from 0.22 to 0.67%. Considering the two
      genes, it was possible to define at least three specific genetic variants in
      Sardinian samples, which we have termed Tm1, Tm2, and Tm3. This is the first
      description of genetic variability in T. multiceps. Further investigations will
      be required to understand to what extent the genetic variability described in
      this paper would be reflected also in phenotypic differences.

PMID- 16614828
TI  - Francisella sp. (Family Francisellaceae) causing mortality in Norwegian cod
      (Gadus morhua) farming.
AB  - In 2004, a new disease was detected in cod (Gadus morhua) in western Norway.
      Affected cod had white granulomas in the visceral organs and skin. A species of
      Francisella was isolated on blood agar plates from moribund cod. The bacterium
      could be grown at temperatures ranging from 6 to 22 degrees C, but did not grow
      at 37 degrees C. Challenge experiments showed that Francisella sp. was the cause
      for the new disease. The 16S rDNA gene sequence from Francisella sp. showed
      99.17% similarity to F. philomiragia, and the 16S-23S ribosomal RNA intergenic
      spacer (249 nt), shows a similarity with that from Francisella isolated from
      tilapia and F. tularensis of 96.8 and 35.9%, respectively. The 23S sequence is
      more similar to F. tularensis, 97.7% (2,862 nt), compared to the tilapia isolate
      96.8% (2,131 nt). The partial putative outer membrane protein (FopA) sequence
      (781 nt) from Francisella sp. shows a similarity with that from F. tularensis and
      F. philomiragia of 77.3 and 98.2%, respectively. Based on sequence data,
      culturing temperatures and pathogenicity for cod, it is suggested that this
      Francisella sp. from cod could be a new species of Francisella, Family
      Francisellaceae.

PMID- 16614829
TI  - Molecular mapping of a nuclear male-sterility gene in sunflower (Helianthus
      annuus L.) using TRAP and SSR markers.
AB  - A nuclear male-sterile mutant, NMS 360, induced by streptomycin from an inbred
      maintainer line HA 89, possesses a single recessive gene, ms9, controlling male
      sterility. The present study identified DNA markers linked to the ms9 gene in an
      F2 population derived from the cross of NMS 360 x RHA 271 and maps the ms9 gene
      to an existing sunflower SSR linkage map. Bulked segregant analysis was performed
      using the target region amplification polymorphism (TRAP) marker technique and
      the simple sequence repeats (SSR) technique. From 444 primer combinations, six
      TRAP markers linked with the ms9 gene were amplified. Two markers, Ts4p03-202 and
      Tt3p09-529, cosegregated with the ms9 gene. The other four markers, To3d14-310,
      Tt3p17-390, Ts4p23-300, and Tt3p09-531, linked with ms9 at a distance of 1.2,
      3.7, 10.3, and 22.3 cM, respectively. Thirty SSR primers from 17 linkage groups
      of a PHA x PHB cultivated sunflower linkage map were screened among the two
      parents and the F2 population. SSR primer ORS 705 of linkage group 10 was tightly
      linked to ms9 at a distance of 1.2 cM. The ms9 gene was subsequently mapped to
      linkage group 10 of the public sunflower SSR linkage map. The markers that were
      tightly linked with the ms9 gene will be useful in marker-assisted selection of
      male-sterile plants among segregating populations, and will facilitate the
      isolation of the ms9 gene by map-based cloning.

PMID- 16614830
TI  - Identification of QTLs for Ralstonia solanacearum race 3-phylotype II resistance
      in tomato.
AB  - Resistance against a Ralstonia solanacearum race 3-phylotype II strain JT516 was
      assessed in a F(2:3) and a population of inbred lines (RIL), both derived from a
      cross between L. esculentum cv. Hawaii 7996 (partially resistant) and L.
      pimpinellifolium WVa700 (susceptible). Resistance criteria used were the
      percentage of wilted plants to calculate the AUDPC value, and bacterial
      colonization scores in roots and stem (hypocotyl and epicotyl) assessed in two
      independent greenhouse experiments conducted during the cool and hot seasons in
      Reunion Island, France. Symptoms were more severe during the cool season trials.
      Heritability estimates in individual seasons ranged from 0.82 to 0.88, depending
      on resistance criterion. A set of 76 molecular markers was used for quantitative
      trait loci (QTL) mapping using the single- and composite- interval mapping
      methods, as well as ANOVA. Four QTLs, named Bwr- followed by a number indicating
      their map location, were identified. They explained from 3.2 to 29.8% of the
      phenotypic variation, depending on the resistance criterion and the season. A
      major QTL, Bwr-6, and a minor one, Bwr-3, were detected in each season for all
      resistance criteria. Both QTLs showed stronger effects in the hot season than in
      the cool one. Their role in resistance to R. solanacearum race 3-phylotype II was
      subsequently confirmed in the RIL population derived from the same cross. Two
      other QTLs, Bwr-4 and Bwr-8, with intermediate and minor effects, respectively,
      were only detected in the hot season, demonstrating that environmental factors
      may strongly influence the expression of resistance against the race 3-phylotype
      II strain JT516. These QTLs were compared with those detected in the RIL
      population against race 1-phylotype I strain JT519 as well as those detected in
      other previous studies in the same genetic background against other race 1
      phylotype I and II strains. This comparison revealed the possible occurrence of
      some phylotype-specific resistance QTLs in Hawaii 7996.

PMID- 16614831
TI  - Microsatellite marker diversity in common bean (Phaseolus vulgaris L.).
AB  - A diversity survey was used to estimate allelic diversity and heterozygosity of
      129 microsatellite markers in a panel of 44 common bean (Phaseolus vulgaris L.)
      genotypes that have been used as parents of mapping populations. Two types of
      microsatellites were evaluated, based respectively on gene coding and genomic
      sequences. Genetic diversity was evaluated by estimating the polymorphism
      information content (PIC), as well as the distribution and range of alleles
      sizes. Gene-based microsatellites proved to be less polymorphic than genomic
      microsatellites in terms of both number of alleles (6.0 vs. 9.2) and PIC values
      (0.446 vs. 0.594) while greater size differences between the largest and the
      smallest allele were observed for the genomic microsatellites than for the gene
      based microsatellites (31.4 vs. 19.1 bp). Markers that showed a high number of
      alleles were identified with a maximum of 28 alleles for the marker BMd1. The
      microsatellites were useful for distinguishing Andean and Mesoamerican genotypes,
      for uncovering the races within each genepool and for separating wild accessions
      from cultivars. Greater polymorphism and race structure was found within the
      Andean gene pool than within the Mesoamerican gene pool and polymorphism rate
      between genotypes was consistent with genepool and race identity. Comparisons
      between Andean genotypes had higher polymorphism (53.0%) on average than
      comparisons among Mesoamerican genotypes (33.4%). Within the Mesoamerican
      parental combinations, the intra-racial combinations between Mesoamerica and
      Durango or Jalisco race genotypes showed higher average rates of polymorphism
      (37.5%) than the within-race combinations between Mesoamerica race genotypes
      (31.7%). In multiple correspondance analysis we found two principal clusters of
      genotypes corresponding to the Mesoamerican and Andean gene pools and subgroups
      representing specific races especially for the Nueva Granada and Peru races of
      the Andean gene pool. Intra population diversity was higher within the Andean
      genepool than within the Mesoamerican genepool and this pattern was observed for
      both gene-based and genomic microsatellites. Furthermore, intra-population
      diversity within the Andean races (0.356 on average) was higher than within the
      Mesoamerican races (0.302). Within the Andean gene pool, race Peru had higher
      diversity compared to race Nueva Granada, while within the Mesoamerican gene
      pool, the races Durango, Guatemala and Jalisco had comparable levels of diversity
      which were below that of race Mesoamerica.

PMID- 16614832
TI  - Assessment of testcross performance and genetic diversity of yellow endosperm
      maize lines derived from adapted x exotic backcrosses.
AB  - Introduction of exotic maize (Zea mays L.) into adapted tropical germplasm may
      enhance genetic variability and lead to greater progress from selection. The
      first objective of this study was to determine if yellow endosperm lines derived
      from adapted x exotic backcrosses contain exotic alleles that are superior to the
      recurrent adapted parental line for yield and other agronomic traits in tropical
      environments. Thirteen exotic yellow maize inbred lines were crossed to an
      adapted orange line (KUSR) and the F1s were backcrossed to KUSR to generate the
      first backcrosses. Fifty BC1F4 lines derived from these backcrosses and the
      recurrent parent were crossed to a common inbred tester (L4001) to form
      testcrosses, which were evaluated at eight environments in Nigeria. Testcrosses
      of the BC-derived lines differed significantly for grain yield and other
      agronomic traits. Only two testcrosses yielded significantly less than L4001 x
      KUSR, with the best 15 testcrosses producing between 289 and 1,056 kg/ha more
      grain yield than L4001 x KUSR. The best testcrosses were similar to or better
      than L4001 x KUSR for other agronomic traits. The second objective of this study
      was to assess the extent of genetic diversity present among the BC-derived lines.
      We genotyped 46 BC-derived lines including KUSR and L4001 with 10 AFLP primer
      pairs and found 491 polymorphic fragments. The average allelic diversity of the
      lines was 0.30 +/- 0.01. The genetic distance of each BC-derived line from KUSR
      ranged between 0.49 and 0.91. The average genetic distance for all pairs of the
      BC-derived lines was 0.68 +/- 0.004, varying from 0.34 to 0.92. The increased
      grain yield and genetic diversity observed in these studies provide evidence that
      exotic germplasm can contribute new alleles to expand the genetic base of
      tropical maize and develop high-yielding hybrids.

PMID- 16614833
TI  - Conditional QTL mapping of oil content in rapeseed with respect to protein
      content and traits related to plant development and grain yield.
AB  - Oil content in rapeseed (Brassica napus L.) is generally regarded as a character
      with high heritability that is negatively correlated with protein content and
      influenced by plant developmental and yield related traits. To evaluate possible
      genetic interrelationships between these traits and oil content, QTL for oil
      content were mapped using data on oil content and on oil content conditioned on
      the putatively interrelated traits. Phenotypic data were evaluated in a
      segregating doubled haploid population of 282 lines derived from the F(1) of a
      cross between the old German cultivar Sollux and the Chinese cultivar Gaoyou. The
      material was tested at four locations, two each in Germany and in China.
      QTLMapper version 1.0 was used for mapping unconditional and conditional QTL with
      additive (a) and locus pairs with additive x additive epistatic (aa) effects.
      Clear evidence was found for a strong genetic relationship between oil and
      protein content. Six QTL and nine epistatic locus pairs were found, which had
      pleiotropic effects on both traits. Nevertheless, two QTL were also identified,
      which control oil content independent from protein content and which could be
      used in practical breeding programs to increase oil content without affecting
      seed protein content. In addition, six additional QTL with small effects were
      only identified in the conditional mapping. Some evidence was apparent for a
      genetic interrelationship between oil content and the number of seeds per silique
      but no evidence was found for a genetic relationship between oil content and
      flowering time, grain filling period or single seed weight. The results indicate
      that for closely correlated traits conditional QTL mapping can be used to dissect
      the genetic interrelationship between two traits at the level of individual QTL.
      Furthermore, conditional QTL mapping can reveal additional QTL with small effects
      that are undetectable in unconditional mapping.

PMID- 16614834
TI  - The effects of subthreshold synchrony on the perception of simultaneity.
AB  - We aimed to examine the effects of subthreshold synchrony and asynchrony on the
      perception of simultaneity. We rendered simultaneous or asynchronous luminance
      changes below detection thresholds by embedding them in a sequence of rapidly
      onsetting flankers. Still, simultaneity of subthreshold luminance changes can
      influence decisions concerning the simultaneity of clearly visible changes in
      luminance: across a range of very brief target SOAs, subthreshold synchrony was
      found to increase the tendency to report 'simultaneity', although simultaneity
      thresholds themselves remained largely uninfluenced. These effects are discussed
      in terms of the early synchronization of sensory mechanisms and the extent to
      which this pattern of synchronization influences the perception of relations
      between events in time.

PMID- 16614835
TI  - Visual perception in a snapshot.

PMID- 16614836
TI  - Rapid onset and long-term inhibition of return in the multiple cuing paradigm.
AB  - Inhibition of return (IOR) refers to the finding that targets at cued locations
      are responded to more slowly than targets at uncued locations when a relatively
      long temporal interval occurs between the two events. In studies which have
      examined the time course of IOR (e.g., Samuel & Kat in Psychonomic Bulletin &
      Review, 10, 897-906, 2003), the effect is generally shown to develop at around
      200 ms and dissipate at around 3,000 ms following a cue. A number of recent
      studies, however, have demonstrated that IOR can develop much more quickly (up to
      50 ms following a cue) and last much longer (up to 13 min following a cue) in
      certain tasks. The present study uses the multiple cuing paradigm to determine
      whether IOR can be observed outside the normally reported temporal boundaries
      (300-3,000 ms) when attention is shifted very quickly (every 15 ms) or very
      slowly (every 1,500 ms) throughout the visual field. IOR was observed as quickly
      as 30 ms following cue onset and as long as 6,000 ms following cue onset.
      Implications for the role of IOR in visual search are discussed.

PMID- 16614837
TI  - Control of neuronal synchrony by nonlinear delayed feedback.
AB  - We present nonlinear delayed feedback stimulation as a technique for effective
      desynchronization. This method is intriguingly robust with respect to system and
      stimulation parameter variations. We demonstrate its broad applicability by
      applying it to different generic oscillator networks as well as to a population
      of bursting neurons. Nonlinear delayed feedback specifically counteracts abnormal
      interactions and, thus, restores the natural frequencies of the individual
      oscillatory units. Nevertheless, nonlinear delayed feedback enables to strongly
      detune the macroscopic frequency of the collective oscillation. We propose
      nonlinear delayed feedback stimulation for the therapy of neurological diseases
      characterized by abnormal synchrony.

PMID- 16614838
TI  - [Unilateral recurring opacity of the corneal epithelium].

PMID- 16614839
TI  - [Increasing incidence of wasp stings in otorhinolaryngological practice].
AB  - BACKGROUND: Wasp sting injuries can be lethal due to generalized reactions and
      edematous obstruction of the upper respiratory system. Due to media reports and
      our own observations, the consequences of the 2004 "plague of wasps" should be
      examined for the ear, nose, and throat (ENT) region. PATIENTS AND METHODS: Wasp
      sting injuries treated during the years 2002 to 2004 were evaluated in a
      retrospective study with respect to frequency, localization, therapy, occurrence
      of allergic reactions, and other complications. RESULTS: In 2002 to 2004, the
      number of patients with wasp sting injuries tripled. The occurrence of stings in
      the ENT region increased from 20% to more than 40%, with a strong rise in enoral
      and endolaryngeal stings after accidental swallowing or inhalation of wasps. The
      medical treatments employed proved the existence of sufficient therapeutic
      strategies. CONCLUSIONS: The treatments demonstrate a clear increase in wasp
      sting injuries in the year 2004. The main climatic cause was the European record
      summer of 2003, in which wasps multiplied.

PMID- 16614840
TI  - [Techniques in otoplasty].
AB  - A great number of surgical techniques for the correction of protruding ears have
      been developed. Their basic concepts originate from Mustarde's suture, the
      scoring technique described by Chongchet, Stenstrom, and Cricelair, and the
      combined suture and scoring technique described by Converse. Techniques for cavum
      rotation and lobuleplasty have also been presented. Indication, diagnostics,
      selection of method, the operative technique itself, and postoperative care are
      described. Advantages and risks of each technique are discussed, and a therapy
      algorithm is proposed.

PMID- 16614841
TI  - [Vestibular evoked myogenic potentials].
AB  - The recording of vestibular evoked myogenic potentials is a relatively new neuro
      otologic method which gives specific information about the function of the
      sacculus and the inferior vestibular nerve on each side separately. The main
      indications for this method are vestibular schwannoma and fistula of the
      labyrinth, involvement of the sacculus or the inferior vestibular nerve in
      Meniere's disease and vestibular neuritis, vertigo of unknown etiology, and
      forensic questions.

PMID- 16614842
TI  - [Vacuum-assisted closure of nonhealing wounds in head and neck reconstructive
      surgery].
AB  - Chronic wounds are characterized by slow or nonexistent wound healing. Usually
      their treatment is expensive. Therefore new concepts in management are of
      interest in order to reduce treatment time and costs. One option is vacuum
      sealing. The concept of topical negative pressure is not new, and many chronic
      nonhealing wounds could be closed successfully with the help of vacuum sealing.
      Until now, there has been no documented case of vacuum sealing in head and neck
      reconstructive surgery. Our case shows the effectiveness of a vacuum-assisted
      device in successful closure of a chronic nonhealing wound in this region.

PMID- 16614843
TI  - [Rare sialadenoma papilliferum in the hard palate: case report and survey of the
      literature].
AB  - Sialadenoma papilliferum is a rare tumour of the salivary glands that usually
      occurs in the oral cavity. Following the course of the salivary glands of the
      oral mucosa, the hard and soft palate are the most common locations of this
      tumor. In the international literature, only a few case reports about this entity
      can be found. We present a 63-year-old patient with a sialadenoma papilliferum
      accidentally found during diagnostic procedures for progredient dysphagia.
      Suffering from infrabifurcal cancer of the oesophagus, the patient had undergone
      partial oesophagectomy 1 year before. Histological verification was performed
      with a tumor biopsy at the border of hard and soft palate, on the right side.
      This case is compared with 39 further cases reported in the literature. The
      therapy of choice is resection of the tumor. Because of the high frequency of
      recurrence, in sano resection should be planned.

PMID- 16614844
TI  - [Patients with chronic rhinosinusitis: disease-specific and general health
      related quality of life].
AB  - BACKGROUND: The negative effect of chronic rhinosinusitis on patient quality of
      life has been generally underappreciated and undervalued. So far, only a few
      studies have examined health-related quality of life at German language patient
      collectives with validated measuring instruments. PATIENTS AND METHODS:
      Preoperatively, 163 patients were included into the study. Three months and 1
      year after functional endonasal sinus surgery 123 and 82 patients, respectively,
      participated in the questioning. To measure health-related quality of life, we
      used version 20 of the German Adapted Version of the Sinonasal Outcome Test and
      the Short Form 36 Health Survey (SF-36). The German normative values of the SF-36
      were used for analysis. RESULTS: Postoperatively, a significant improvement in
      health-related quality of life was determined on all scales of both measuring
      instruments. Comparing our data with the German normative values of the SF-36, we
      found a lasting approximation of the average assessment levels in seven of eight
      scales. CONCLUSION: Functional endonasal sinus surgery leads to significant
      improvements in disease-specific and general quality of life in patients with
      chronic rhinosinusitis.

PMID- 16614845
TI  - [Paediatric laryngotracheal stenosis: pattern of care in Germany].
AB  - BACKGROUND: Stenoses of the larynx and upper trachea in the pediatric population
      require a multidisciplinary approach and center-based treatment. Patterns of care
      and treatment strategies in Germany were evaluated using a standardized
      questionnaire. MATERIAL AND METHODS: A questionnaire was transmitted by telefax
      to 141 departments of Otorhinolaryngology (ORL) and to 214 pediatric (PED)
      departments. Using primarily multiple-choice questions variables regarding
      caseload, surgical techniques, cooperating institutions, criteria for surgical
      indications and subjective assessment of success rates were investigated.
      RESULTS: The response rate was 55% (ORL) and 46% (PED), respectively, 34% of the
      replying ORL departments were offering tracheal surgery in children, with most of
      them using advanced surgical techniques. In 12 ORL departments 1-3 cases per year
      were operated, in 6 ORL departments more than 6 cases per year and 3 ORL
      departments were perceived as specialized centers for pediatric airway surgery by
      their peers. However, 41% of the PED departments were unable to identify a center
      for pediatric airway surgery. CONCLUSION: In Germany, surgery for pediatric
      airway stenoses is not primarily focused on treatment centers. There is a
      significant information gap among German pediatricians regarding success rates of
      reconstructive airway surgery and available centers offering surgical therapy for
      this population. Several factors offer potential to be optimized in the care for
      children with a compromised airway and improving communication between
      otolaryngologists and pediatricians should be a primary goal in the future.

PMID- 16614846
TI  - Complete remission upon bortezomib-dexamethasone therapy in three heavily
      pretreated multiple myeloma patients relapsing after allogeneic stem cell
      transplantation.

PMID- 16614847
TI  - Are changes in urinary parameters during pregnancy clinically significant?
AB  - We aimed to objectively determine changes in the various urinary parameters along
      with CaOx saturation level during pregnancy. The study included 15 pregnant women
      who had no known diseases and were taking no medication except prenatal
      supplements. Mean age of the patients was 26 years (range 20-30). In all of them,
      this study was carried out in each trimester and 3 months post partum. All
      participants were followed up, and blood and urine samples were obtained during
      the pregnancy and during 3 months post partum. All subjects collected 24-h urine
      samples. The pregnant women had hypercalciuria in all three trimesters. Except
      for the first trimester, urine calcium levels in all trimesters were
      significantly higher when compared with the post-partum period (P<0.01 for second
      trimester, P<0.05 for third trimester). Urine oxalate level in post-partum period
      was significantly higher than urine oxalate levels in each trimester (P<0.05).
      The urine citrate levels were similarly higher than normal levels in three
      trimesters. Urine citrate level of the post-partum period was in normal reference
      ranges. This difference was not statistically significant (P>0.05). We believe
      that hypercalciuria encountered at pregnancy is a reversible physiologic
      condition. Also, citrate and magnesium as urinary inhibitors increased in urine
      during gestation preventing stone formation. We think that long time periods are
      needed for hypercalciuria to be able to lead to the formation of urinary calculi
      in pregnant women (except women having a positive family history). Therefore, we
      think that the pregnancy alone does not predispose to a suitable condition for
      calculi.

PMID- 16614848
TI  - A combination therapy with transarterial chemo-lipiodolization and systemic chemo
      infusion for large extensive hepatocellular carcinoma invading portal vein in
      comparison with conservative management.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) invading the portal vein is a medical
      challenge. We evaluated the therapeutic efficacy of a combination of
      transarterial and systemic chemo-infusion for large HCC with portal vein
      thrombosis (PVT) compared with conservative management. PATIENTS AND METHODS:
      This was a case-control cohort study of 103 consecutive patients with Child-Pugh
      class A who had a large (>10 cm) HCC with PVT. The patients were assigned to
      receive either combined transarterial epirubicin (50 mg/m(2)) plus cisplatin (60
      mg/m(2)) chemo-lipiodolization and systemic 5-fluorouracil (200 mg/m(2)) chemo
      infusion (ECF regimen) at monthly intervals (n=80) or conservative management
      (n=23). RESULTS: The objective tumor response (21.3 vs. 0%, P=0.011) and overall
      survival (8.7 vs. 3.5 months, P<0.001) were significantly better in the treatment
      group than in the conservative group. The prognostic factors for survival were
      tumor type (P=0.007), bilobar involvement (P=0.001), distant metastasis (P=0.009)
      and objective tumor response (P<0.001) for the treatment group. Survival benefits
      with the treatment were also maintained in each subgroup after stratification of
      these variables. CONCLUSIONS: This study suggests that when the hepatic function
      is preserved, a therapeutic strategy could be more beneficial than conservative
      management for such a large extensive HCC. As a therapeutic option, a combination
      therapy using ECF regimen may provide a significantly better tumor response and
      survival benefit in patients with large HCC invading the portal vein.

PMID- 16614849
TI  - Phase II trial of a 2-h infusion of gemcitabine plus carboplatin as first-line
      chemotherapy for advanced non-small-cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy and safety of the combination of using
      gemcitabine as a rate infusion of 10 mg/m(2) per min with carboplatin in front
      line chemonaive patients with advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: Fifty-four chemonaive patients with stage IIIB or IV NSCLC
      have been included, 44 males and 10 females, with a median age 63 years (range 19
      75). Thirty-two (59%) patients had adenocarcinoma, 13 (24%) squamous cell, 1 (2%)
      large cell carcinoma and 8 (15%) others. Eight (15%) had stage IIIB and 46 (85%)
      stage IV. Treatment was consisted of 1,200 mg/m(2) gemcitabine given as a 2-h
      continuous infusion (10 mg/m(2) per min) on days 1 and 8 of each cycle an AUC 5
      carboplatin as on day 1, repeating each cycle for every 21 days. A total of 223
      chemotherapy cycles were administered, with a median of four cycles per patient
      (range 1-6), and 15 (28%) patients received all six cycles. RESULTS: Of the 54
      patients enrolled, all were evaluated for toxicity and 51 assessed for response.
      The overall response rate was 41% (95% confidence interval, 28-57%) with complete
      and partial responses of 4 and 37%, respectively. The median time to disease
      progression was 5.0 months (95% CI, 3.7-6.3 months), and median overall survival
      time was 11.5 months (95% CI, 9.9-13.1 months). One-year survival was 42%. The
      main grade 3-4 toxicity (according to the WHO scale) consisted of neutropenia
      (56%) and thrombocytopenia (57%). Patients were required platelet transfusion in
      27 cycles (12%) and hematopoietic growth factors support care in 56 (25%) cycles.
      No bleeding episodes were recorded. Grade 3 nausea/vomiting occurred in 6% and
      grade 1-2 skin rash occurred in 43%. CONCLUSIONS: Prolonged gemcitabine infusion
      combined with carboplatin is manageable and tolerated, and its efficacy is
      similar to that of other chemotherapeutic schemes used for NSCLC treatment.

PMID- 16614850
TI  - RNAi-mediated knockdown of aldehyde dehydrogenase class-1A1 and class-3A1 is
      specific and reveals that each contributes equally to the resistance against 4
      hydroperoxycyclophosphamide.
AB  - PURPOSE: Aldehyde dehydrogenases class-1A1 (ALDH1A1) and class-3A1 (ALDH3A1) have
      been associated with resistance to cyclophosphamide (CP) and its derivatives. We
      have previously reported the downregulation of these enzymes by all-trans
      retinoic acid (ATRA). METHODS: In this study, we used siRNA duplexes as well as
      retrovirally expressed siRNA to knockdown one or both enzymes together in A549
      lung cancer cell line in order to investigate the role of each one in mediating
      the resistance and the effect of the addition of ATRA. RESULTS: The results show
      that significant and specific knockdown of each enzyme can be achieved and that
      each one contributes similarly to cell resistance to 4
      hydroperoxycyclophosphamide (4-HC), an active derivative of CP. Added effects
      were seen when both enzymes were inhibited. The addition of ATRA also exhibited
      additional inhibitory effects on ALDH activity and increased 4-HC toxicity when
      added to single siRNA aimed at one of the enzymes. On the other hand, ATRA had
      minimal and insignificant additional inhibitory effects on ALDH enzyme activity
      when added to a combination of siRNAs against both enzymes, but still increased 4
      HC toxicity beyond that seen with RNAi-mediated inhibition of both enzymes
      together. CONCLUSIONS: We conclude that both enzymes, ALDH1A1 and ALDH3A1 will
      need to be blocked in order to achieve the highest sensitivity to 4-HC.
      Furthermore, ATRA increases 4-HC toxicity even when added to a combination of
      siRNAs against both enzymes, thus suggesting additional mechanisms by which ATRA
      can increase drug toxicity.

PMID- 16614851
TI  - Optimizing the factors which modify thermal enhancement of melphalan in a
      spontaneous murine tumor.
AB  - BACKGROUND: Hyperthermia enhances the cytotoxicity of some chemotherapeutic
      agents. Both clinical and laboratory studies suggest melphalan may be an
      important drug when hyperthermia is added to chemotherapy treatments. Factors
      that may modify the thermal enhancement of melphalan were studied to optimize its
      clinical use with hyperthermia. METHODS: The tumor studied was an early
      generation isotransplant of a spontaneous C3Hf/Sed mouse fibrosarcoma, Fsa-II.
      All studies were performed under supervision of the Animal Care and Use
      Committee. Hyperthermia was administered by immersing the tumor-bearing foot into
      a constant temperature water bath. Four factors were studied: duration of
      hyperthermia, sequencing of hyperthermia and melphalan, intensity of
      hyperthermia, and tumor size. To study duration of hyperthermia tumors were
      treated at 41.5 degrees C for 30 or 90 min immediately after intraperitoneal
      administration of melphalan. For sequencing of hyperthermia and melphalan,
      animals received hyperthermia treatment of tumors for 30 min at 41.5 degrees C
      immediately after drug administration, both immediately and 3 h after
      administration of drug or only at 3 h after administration of drug. Intensity of
      hyperthermia was studied using heat treatment of tumors for 30 min at 41.5 or
      43.5 degrees C immediately following drug administration. Effect of tumor size
      was studied by delaying experiments until three times the tumor volume (113 mm3)
      was observed. Treatment of tumors was for 30 min at 41.5 degrees C immediately
      following drug administration. Tumor response was studied by the mean tumor
      growth time. RESULTS: Hyperthermia in the absence of melphalan had a small but
      significant effect on tumor growth time at 43.5 degrees C but not at 41.5 degrees
      C. Hyperthermia at 41.5 degrees C immediately after melphalan administration
      doubled mean tumor growth time at 30 min and caused a threefold increase at 90
      min (P=0.0002) when compared to tumors treated with melphalan alone at room
      temperature. Application of hyperthermia for one-half hour immediately following
      drug administration was the most effective in delaying tumor growth. No
      significant difference in mean tumor growth time was observed with an increase in
      temperature from 41.5 to 43.5 degrees C. For large tumors heat alone and
      melphalan alone caused a moderate increase in tumor growth delay. These effects
      in large tumors were greatly increased by a combination of chemotherapy and
      hyperthermia. CONCLUSIONS: From our data it would appear that the administration
      of intraperitoneal melphalan immediately prior to 90 min of heat at 41.5 degrees
      C may optimize anti-neoplastic activity. These data may be useful in formulating
      clinical protocols in which melphalan and heat are combined.

PMID- 16614852
TI  - Fine-tuning of cross-bridge kinetics in cardiac muscle of rat and mouse by myosin
      light chain isoforms.
AB  - Cross-bridge kinetics underlying stretch-induced force transients was studied in
      cardiac muscle strips with different myosin heavy chain (MHC) and myosin light
      chain (MLC) isoforms. The force transients were induced by stepwise stretches of
      maximally Ca(2+)-activated skinned muscle strips. The MHC and MLC isoforms were
      analyzed by electrophoreses after the mechanical experiments. Muscle strips of
      euthyroid rats and mice exclusively containing alpha-MHC were used. In addition,
      muscle strips of hyper- and hypothyroid rats containing different combinations of
      MHC and MLC isoforms were used. The thyroid hormone is known to alter the
      expression of MHC but not of MLC isoforms. In muscle strips containing
      exclusively alpha-MHC, atrial MLC isoforms (all atria of rats and mice) were
      associated with about 30% faster kinetics than ventricular MLC isoforms
      (ventricles of hyperthyroid rats and some muscle strips of ventricles of
      euthyroid rats and mice). On the other hand, in muscle strips containing
      exclusively ventricular MLC isoforms, alpha-MHC (ventricles of hyperthyroid rats)
      was associated with about 2.6 times faster kinetics than beta-MHC (ventricles of
      hypothyroid rats). We conclude that the MLC isoforms fine-tune cross-bridge
      kinetics, which underlies stretch-induced force transients, whereas the MHC
      isoforms mainly determine this kinetics. The effect of MLC isoforms on the cross
      bridge kinetics may partially contribute to the faster twitch contraction in
      atria than in ventricles. Furthermore, it may play a role in various
      cardiomyopathies where atrial MLC isoforms are partially expressed in ventricles
      or ventricular MLC isoforms are partially expressed in atria.

PMID- 16614853
TI  - Herniated intervertebral disc associated with a lumbar spine dislocation as a
      cause of cauda equina syndrome: a case report.
AB  - To report a case of Cauda Equina syndrome with the completion of the paralysis
      after the reduction of a L4L5 dislocation due to a herniated disc. Although
      several articles have described a post-traumatic disc herniation in the cervical
      spinal canal, this is not well known in the lumbar region. A 30-year-old man was
      admitted to the emergency room with blunt trauma to the chest and abdomen with
      multiple contusions plus a dislocation of L4-L5 with an incomplete neurological
      injury. After an emergency open reduction and instrumentation of the dislocation,
      the patient developed a complete cauda equina syndrome that has resulted from an
      additional compression of the dural sac by a herniated disc. In a dislocation of
      the lumbar spine, MRI study is mandatory to check the state of the spinal canal
      prior to surgical reduction. A posterior approach is sufficient for reduction of
      the vertebral displacement, however an intra-canal exploration for bony or disc
      material should be systematically done.

PMID- 16614854
TI  - Altered cerebral blood flow in chronic neck pain patients but not in whiplash
      patients: a 99mTc-HMPAO rCBF study.
AB  - A cross-sectional study to investigate regional cerebral blood flow (rCBF) in
      patients with chronic whiplash syndrome and chronic neck pain patients without
      previous history of trauma along with a healthy control group. Chronic neck pain
      is a common disorder and a history of cervical spine injury including whiplash
      trauma constitute a risk factor for persistent neck pain. The aetiology of the
      late whiplash syndrome is unknown with no specific diagnostic criteria based on
      imaging, physiological, or psychological examination. Earlier studies indicate a
      parieto-occipital hypoperfusion but it is unclear if the hypoperfusion represents
      a response to chronic pain. The rCBF was monitored in 45 patients with chronic
      neck pain: 27 cases with chronic whiplash syndrome and 18 age and gender matched
      cases with non-traumatic chronic neck pain. The rCBF was estimated with single
      photon emission computed tomography (SPECT) using technetium-99m
      hexamethylpropylene amine oxime (HMPAO). The non-traumatic patients displayed
      rCBF changes in comparison with the whiplash group and the healthy control group.
      These changes included rCBF decreases in a right temporal region close to
      hippocampus, and increased rCBF in left insula. The whiplash group displayed no
      significant differences in rCBF in comparison with the healthy controls. The
      present study suggests different pain mechanisms in patients with chronic neck
      pain of non-traumatic origin compared to those with chronic neck pain due to a
      whiplash trauma.

PMID- 16614855
TI  - Validity and interobserver agreement of a new radiographic grading system for
      intervertebral disc degeneration: Part II. Cervical spine.
AB  - A new radiographic grading system for a more objective assessment of lumbar
      intervertebral disc degeneration has been described and tested in Part I of this
      study. The aim of the present Part II of the study was to adapt this system to
      the cervical spine, and to test it for validity and interobserver agreement. Some
      modifications of the grading system described in Part I were necessary to make it
      applicable to the cervical spine. Its basic structure, however, stayed untouched.
      The three variables "Height Loss", "Osteophyte Formation" and "Diffuse Sclerosis"
      first have to be graded individually. Then, the "Overall Degree of Degeneration"
      is assigned on a four-point scale from 0 (no degeneration) to 3 (severe
      degeneration). For validation, the radiographic degrees of degeneration of 28
      cervical discs were compared to the respective macroscopic ones, which were
      defined as "real" degrees of degeneration. The interobserver agreement was
      determined between one experienced and one unexperienced observer using the
      radiographs of 57 cervical discs. Quadratic weighted Kappa coefficients (kappa)
      with 95% confidence limits (95% CL) were used for statistical evaluation. The
      validation of the new version of the radiographic grading system showed a
      moderate agreement with the "real", macroscopic overall degree of degeneration
      (kappa=0.599, 95% CL 0.421-0.786). In 64% of all discs the "real" overall degree
      of degeneration was underestimated but never overestimated. This underestimation,
      however, was much less pronounced and the Kappa coefficients were significantly
      higher for the three variables: Height Loss, Osteophyte Formation, and Diffuse
      Sclerosis separately. The agreement between the radiographic ratings of the
      experienced and the unexperienced observer was substantial for the overall degree
      of degeneration (kappa=0.688, 95% CL 0.580-0.796), almost perfect for the
      variable, Height Loss, moderate for Osteophyte Formation and fair for Diffuse
      Sclerosis. In conclusion, we believe that the new version of the radiographic
      grading system is a sufficiently valid and reliable tool to quantify the degree
      of degeneration of individual cervical intervertebral discs. In comparison to the
      version for the lumbar spine described in Part I, however, a slightly higher
      tendency to underestimate the "real" overall degree of degeneration and somewhat
      higher interobserver differences have to be expected.

PMID- 16614856
TI  - Three dimensional finite element analysis of the pediatric lumbar spine. Part II:
      biomechanical change as the initiating factor for pediatric isthmic
      spondylolisthesis at the growth plate.
AB  - A non-linear 3-dimensional finite element pediatric lumbar spine model with
      vertebral growth plate and apophyseal bony ring was developed. Lumbar
      spondylolysis was simulated in the model. The Von Mises stresses in the
      structures surrounding the vertebral growth plate, including apophyseal bony ring
      and osseous endplate were calculated in various loading modes. Instantaneous axis
      of rotation (IAR) path from flexion to extension was also analyzed. The results
      were compared with those of the intact model and the literature. The IAR path was
      at the posterior disc-endplate space of the lower vertebra in the intact spine,
      and moved cranially towards the upper-posterior disc space in the lytic spine.
      This was in agreement with in vivo radiological data by Sakamaki et al. [19].
      During various loading modes, stresses in the spondylolytic pediatric model were
      higher than that of the intact model; ranging from 1.1 to 6.0 times, with the
      highest value in extension at the growth plate. In conclusion, FE models indicate
      that stress concentrations in the lytic model increase at the growth plate which
      may lead to physis stress fracture leading to spondylolisthesis.

PMID- 16614857
TI  - Three-dimensional finite element analysis of the pediatric lumbar spine. Part I:
      pathomechanism of apophyseal bony ring fracture.
AB  - The purpose of this study was to (1) develop a three-dimensional, nonlinear
      pediatric lumbar spine finite element model (FEM), and (2) identify the
      mechanical reasons for the posterior apophyseal bony ring fracture in the
      pediatric patients. The pediatric spine FE model was created from an
      experimentally validated three-dimensional adult lumbar spine FEM. The size of
      the FEM was reduced to 96% taking into account of the ratio of the sitting height
      of an average 14-years-old children to that of an adult. The pediatric spine was
      created with anatomically specific features like the growth plate and the
      apophyseal bony ring. For the stress analyses, a 10-N m moment was applied in all
      the six directions of motion for the lumbar spine. A preload of 351 N was applied
      which corresponds to the mean body weight of the 14-years-old group. The stresses
      at the apophyseal bony ring, growth plate and endplate were calculated. The
      results indicate that the structures surrounding the growth plate including
      apophyseal bony ring and osseous endplate were highly stressed, as compared to
      other structures. Furthermore, posterior structures in extension were in
      compression whereas in flexion they were in tension, with magnitude of stresses
      higher in extension than in flexion. Over time, the higher compression stresses
      along with tension stresses in flexion may contribute to the apophyseal ring
      fracture (fatigue phenomena).

PMID- 16614858
TI  - Unusual hydrophobic linker region of beta-glucosidase (BGLII) from Thermoascus
      aurantiacus is required for hyper-activation by organic solvents.
AB  - A gene encoding a putative beta-glucosidase was isolated from Thermoascus
      aurantiacus IFO9748 and designated as bgl2. The recombinant enzyme showed beta
      glucosidase activity when p-nitrophenyl-beta-glucose (pNP-Glc) was used as
      substrate. We also found that the enzyme activity was increased in the presence
      of organic solvents. An addition of 20 % (v/v) 1-octanol resulted in 54-fold
      higher activity of pNP-Glc hydrolysis, and transglycosylation activity was also
      found to be activated. The results of tryptophan fluorescence spectral analysis
      revealed the changes in the tertiary structure of the enzyme in the presence of 1
      hexanol that may cause increased enzyme activity. BGLII has a distinctive
      hydrophobic linker region between N- and C-terminal domains. A chimeric enzyme in
      which the linker region was substituted by the corresponding region of another
      beta-glucosidase failed to be activated by organic solvents, suggesting that the
      hydrophobic linker region may act as a molecular switch in BGLII.

PMID- 16614859
TI  - Characterization of bacterial beta-carotene 3,3'-hydroxylases, CrtZ, and P450 in
      astaxanthin biosynthetic pathway and adonirubin production by gene combination in
      Escherichia coli.
AB  - beta-Carotene hydroxylase (CrtZ) is one of rate-limiting enzymes for astaxanthin
      production. A complementation analysis was conducted using Escherichia coli
      transformants to compare the catalytic efficiency of bacterial CrtZ from
      Brevundimonas sp. SD212, Paracoccus sp. PC1 (formerly known as Alcaligenes sp. PC
      1), Paracoccus sp. N81106 (Agrobacterium aurantiacum), Pantoea ananatis (Erwinia
      uredovora 20D3), marine bacterium P99-3, and P450 monooxygenase (CYP175A1) from
      Thermus thermophilus HB27. Each crtZ or CYP175A1 gene was expressed in E. coli
      transformants synthesizing canthaxanthin and beta-carotene due to the respective
      presence of plasmids pAC-Cantha and pACCAR16DeltacrtX. The carotenoids that
      accumulated in the resulting recombinant E. coli cells were examined by
      chromatographic and spectroscopic analyses. E. coli carrying Brevundimonas sp.
      SD212 crtZ showed the highest astaxanthin production efficiency among the
      transformants examined, while there was no significant difference in the
      catalytic efficiency for conversion from beta-carotene to zeaxanthin. Recombinant
      E. coli expressing the CYP175A1 gene, in addition to the genes for canthaxanthin
      synthesis, surprisingly accumulated adonirubin (phoenicoxanthin) as the main
      product, although the other recombinant E. coli did not accumulate any
      adonirubin. The present results suggest that the Brevundimonas sp. SD212 crtZ and
      T. thermophilus HB27 CYP175A1 genes could, respectively, be used for the
      efficient production of astaxanthin and adonirubin in heterologous hosts.

PMID- 16614860
TI  - Microbial aldolases as C-C bonding enzymes--unknown treasures and new
      developments.
AB  - Aldolases are a specific group of lyases that catalyze the reversible
      stereoselective addition of a donor compound (nucleophile) onto an acceptor
      compound (electrophile). Whereas most aldolases are specific for their donor
      compound in the aldolization reaction, they often tolerate a wide range of
      aldehydes as acceptor compounds. C-C bonding by aldolases creates stereocenters
      in the resulting aldol products. This makes aldolases interesting tools for
      asymmetric syntheses of rare sugars or sugar-derived compounds as iminocyclitols,
      statins, epothilones, and sialic acids. Besides the well-known fructose 1,6
      bisphosphate aldolase, other aldolases of microbial origin have attracted the
      interest of synthetic bio-organic chemists in recent years. These are either
      other dihydroxyacetone phosphate aldolases or aldolases depending on
      pyruvate/phosphoenolpyruvate, glycine, or acetaldehyde as donor substrate.
      Recently, an aldolase that accepts dihydroxyacetone or hydroxyacetone as a donor
      was described. A further enlargement of the arsenal of available chemoenzymatic
      tools can be achieved through screening for novel aldolase activities and
      directed evolution of existing aldolases to alter their substrate- or
      stereospecifities. We give an update of work on aldolases, with an emphasis on
      microbial aldolases.

PMID- 16614861
TI  - hTERT immunopositivity patterns in the normal brain and in astrocytic tumors.
AB  - Accumulating data about the impact of hTERT in astrocytic tumor carcinogenesis
      and recent evidence about its association with disease outcome prompt the
      evaluation of this molecule with methods applicable in routine pathology
      practice. In this study, we investigated hTERT protein expression with
      immunohistochemistry (IHC) and the NCL-hTERT antibody in 49 astrocytic tumors.
      Results were validated with the assessment of hTERT mRNA (relative
      quantification, identification of splice variants, in situ hybridization).
      Specific nuclear hTERT immunostaining patterns (IPs) were characterized as
      patterns As (single large dot) and Am (multiple dots) without nucleoplasm
      staining and pattern B (nucleoplasm staining with or without dots), corresponding
      to low and high relative hTERT expression values (P<0.0001). Low- and high-grade
      astrocytic tumors were found positive for hTERT in 74 and 85% of cases,
      respectively. Heterogeneity in the distribution of hTERT-positive cells was
      observed in all tumors. The prevailing nuclear IPs differed significantly between
      pilocytic astrocytomas (pattern As) and the rest of histologic types up to
      glioblastoma (patterns Am and B) (P<0.0001). The described nuclear IPs were also
      observed in non-neoplastic cells. Positive endothelial cells were found in
      astrocytic tumors of all grades, even when tumor cells showed no hTERT
      immunoreactivity. A subset of mature normal neurons was positive for hTERT
      (pattern As), suggesting a role for this molecule in neuronal maintenance in the
      adult brain. The nuclear hTERT IPs described here may reflect the functional
      status of non-neoplastic brain and neoplastic astrocytic cells and support the
      model of a continuum in the development of glioblastomas from diffuse fibrillary
      astrocytomas.

PMID- 16614862
TI  - BSE immunohistochemical patterns in the brainstem: a comparison between UK and
      Italian cases.
AB  - The continuous monitoring of bovine spongiform encephalopathy (BSE) cases is an
      integral component of European research and surveillance programmes, to ensure
      that any changes in the presentation of transmissible spongiform encephalopathies
      (TSE) in cattle can be detected and defined. Monitoring is generally limited to
      the brainstem at the level of the obex, for reasons of practicality, safety and
      cost. Demonstration of disease-specific prion protein (PrP(d)) by
      immunohistochemistry is currently the most widely used confirmatory tool for both
      active and passive surveillance. This study assessed PrP(d) immunostaining in the
      brainstems (obex) of cattle with BSE in the UK and Italy. Immunoreactivity
      'profiles' were created for each case based on the nature of the immunostaining,
      its relative intensity and precise neuroanatomical location. This study compares
      the obex immunostaining patterns of Italian cases (only active surveillance) and
      two UK groups (both active and passive surveillance). The neuroanatomical
      distribution and relative intensity of PrP(d) was highly reproducible in all
      cases. The overall staining intensity varied widely but was generally stronger in
      the active than in the passive surveillance populations. The conclusion to be
      drawn from this comparative study is that the pattern of immunopathology in these
      routine screening samples for BSE diagnosis and surveillance is the same in the
      UK and Italy, whether or not the animal was displaying typical, or indeed any,
      clinical signs at the time of sampling. This indicates that the current
      confirmatory diagnostic strategy remains appropriate for active surveillance
      applications.

PMID- 16614863
TI  - Two-year clinical performance of cast gold vs ceramic partial crowns.
AB  - Cast gold partial crowns (CGPC) are an accepted means of restoring posterior
      teeth with extended lesions. However, for esthetic reasons, CGPC are being
      increasingly substituted with partial ceramic crowns (PCC). The aim of the
      present prospective split-mouth study was to compare the clinical performance of
      PCC and CGPC. There were 29 patients (male 12, female 17) who participated in the
      investigation for a total of 58 restorations. In each patient, one CGPC (Degulor
      C) and one PCC (Vita MarkII/Cerec III) were placed. CGPC were inserted using
      conventional zinc-phosphate cement (Harvard); PCC were adhesively luted to the
      cavities (Variolink II/Excite). The restorations were clinically rated using
      modified United States Public Health Service (USPHS) criteria at baseline and 1
      and 2 years after placement. The median patient age was 38 years (range 25-54).
      There were 29 of the CGPC and 14 PCC placed in molars, while 15 PCC were placed
      in premolars. All patients were available for the 1- and the 2-year recall. One
      PCC (1.7%) failed and had to be replaced after 2 years in situ. The rest of the
      restorations were functional without need of replacement. The evaluation using
      USPHS criteria revealed no statistically significant differences between CGPC and
      PCC with the exception of anatomic form: PCC showed occlusal chipping in two
      cases without need of replacement. From these data, it can be concluded that PCC
      may provide an esthetic and tissue-conservative alternative to CGPC. However,
      long-term studies comparing the clinical performance and longevity of cast gold
      and ceramic partial crowns for posterior teeth are desirable.

PMID- 16614864
TI  - What can we learn about the lipid vesicle structure from the small-angle neutron
      scattering experiment?
AB  - Small-angle neutron scattering (SANS) on the unilamellar vesicle (ULV)
      populations (diameter 500 and 1,000 A) in D2O was used to characterize lipid
      vesicles from dimyristoylphosphatidylcholine (DMPC) at three phases: gel Lbeta',
      ripple Pbeta' and liquid Lalpha. Parameters of vesicle populations and internal
      structure of the DMPC bilayer were characterized on the basis of the separated
      form factor (SFF) model. Vesicle shape changes from nearly spherical in the
      Lalpha phase to elliptical in the Pbeta' and Lbeta' phases. This is true for
      vesicles prepared via extrusion through pores with the diameter 500 A. Parameters
      of the internal bilayer structure (thickness of the membrane and the hydrophobic
      core, hydration and the surface area of the lipid molecule) were determined on
      the basis of the hydrophobic-hydrophilic (HH) approximation of neutron scattering
      length density across the bilayer rhox and of the step function (SF)
      approximation of rhox. DMPC membrane thickness in the Lalpha phase (T = 30
      degrees C) demonstrates a dependence on the membrane curvature for extruded
      vesicles. Prepared via extrusion through 500 A diameter pores, vesicle population
      in the Lalpha phase has the following characteristics: average value of minor
      semi-axis 266 +/- 2 A, ellipse eccentricity 1.11 +/- 0.02, polydispersity 26%,
      thickness of the membrane 48.9 +/- 0.2 A and of the hydrophobic core 19.9 +/- 0.4
      A, surface area 60.7 +/- 0.5 A2 and number of water molecules 12.8 +/- 0.3 per
      DMPC molecule. Vesicles prepared via extrusion through pores with the diameter
      1,000 A have polydispersity of 48% and membrane thickness of 45.5 +/- 0.6 A in
      the Lalpha phase. SF approximation was used to describe the DMPC membrane
      structure in Lbeta' (T = 10 degrees C) and Pbeta' (T = 20 degrees C) phases.
      Extruded DMPC vesicles in D2O have membrane thickness of 49.6 +/- 0.5 A in the
      Lbeta' phase and 48.3 +/- 0.6 A in the Pbeta' phase. The dependence of the DMPC
      membrane thickness on temperature was restored from the SANS experiment.

PMID- 16614865
TI  - [Detlev Ploog (1920 through 2005)].

PMID- 16614866
TI  - [EURAP: the European Registry of Antiepileptic Drugs and Pregnancy].
AB  - All old-generation antiepileptic drugs (AEDs) are considered to be teratogenic.
      In Germany, one out of 200 pregnant women (0.5%) is treated with AEDs for
      epilepsy. The risk of major malformations following exposure to AEDs during the
      first trimester of pregnancy is two to three times the rate reported in the
      general population, which is estimated at 2-3%. The risks associated with the
      treatment of epilepsy during pregnancy are therefore of major concern to all
      women of childbearing potential with epilepsy. Data on the comparative
      teratogenicity of these AEDs in humans are, however, conflicting, mainly due to
      inadequate sample sizes and other methodological shortcomings of previous
      studies. The teratogenic potential of newer AEDs is even less well known, which
      prevents a rational approach to AED treatment in women of childbearing potential.
      The European Registry of Antiepileptic Drugs and Pregnancy is a prospective
      international multicentre study of pregnancies with AEDs. In Germany the project
      was started in 2001 and so far more than 500 pregnancies have been enrolled. The
      enrollment rate is 4% of 4,000 pregnancies with AEDs reported annually.

PMID- 16614867
TI  - Nuclear DNA content of Vitis vinifera cultivars and ploidy level analyses of
      somatic embryo-derived plants obtained from anther culture.
AB  - Flow cytometry was employed to determine the ploidy level of Vitis vinifera L.
      somatic embryo-derived plants obtained from anther culture. Only one among the 41
      analysed plants (2.4%) presented somaclonal variation (tetraploidy); the other
      plants were diploid. No significant differences (P<or=0.05) were detected between
      diploid and parental field plants. No haploid or aneuploid plants were observed.
      The nuclear DNA content of nine V. vinifera cultivars was also estimated using
      flow cytometry. A non-significant variation was found among the cultivars, with
      DNA content ranging from 1.17 pg/2C (cv. 'Tinta Barroca' and 'Viosinho') to 1.26
      pg/2C (cv. 'Cabernet Sauvignon'). These results and previous studies on other
      Vitis species suggest that Vitis genome is stable with regard to nuclear DNA
      content.

PMID- 16614868
TI  - A pituitary abscess showing high signal intensity on diffusion-weighted imaging.
AB  - The utility of diffusion-weighted imaging (DWI) for the diagnosis of intracranial
      abscesses has already been established. However, the use of DWI for pituitary
      abscesses has not been previously reported. We present a case of postoperative
      pituitary abscess in which T1-weighted and T2-weighted magnetic resonance imaging
      (MRI) revealed a supra-sellar cystic mass, with the cyst contents showing high
      intensity on DWI. This case suggests that DWI is useful for the diagnosis of
      pituitary abscesses.

PMID- 16614869
TI  - Podospora anserina target of rapamycin.
AB  - We have isolated the Podospora anserina TOR gene. The PaTOR protein displayed
      strong identities with TOR proteins from other eukaryotes especially in the FRB
      domain and the kinase domain. Genome analysis suggests that a single TOR gene
      exists in Podospora. The serine residue known to be one site of missense
      mutations conferring rapamycin resistance in other organisms is conserved in the
      PaTOR protein (S1895). A PaTOR-S1895R mutated allele has been constructed and
      introduced in the wild-type strain, as expected strains expressing the PaTOR
      S1895R gene become resistant to rapamycin. The dominance of the PaTOR-S1895R
      allele indicates that apparently the mutation does not impair the kinase
      activity. We confirm that all cytological modifications associated with rapamycin
      treatment in Podospora are indeed mediated by PaTOR. We conclude that the PaTOR
      gene is likely to be essential and that rapamycin treatment might be useful to
      further investigate rapamycin-sensitive TOR functions in Podospora and especially
      newly identified rapamycin-sensitive functions such as the autophagy-independent
      control of vacuole remodeling and septation.

PMID- 16614870
TI  - Matrix proteins in the outer shells of molluscs.
AB  - The shells of molluscs are composed mainly of calcium carbonate crystals, with
      small amounts of matrix proteins. For more than 50 years, they have attracted
      attention for their unique mechanical and biological properties. Only recently,
      however, have researchers begun to realize that it is the matrix proteins that
      control the formation of calcium carbonate crystals and play key roles in their
      extraordinary properties, despite the fact that matrix proteins comprise less
      than 5% of the shell weight. This article reviews the matrix proteins identified
      to date from the shells of molluscs, their structural characteristics, and their
      roles in shell formation. Some suggestions are given for further investigation
      based on the summary and analysis.

PMID- 16614872
TI  - Differential gene expression in Symbiodinium microadriaticum clade B following
      stress.
AB  - Coral bleaching is caused by the loss of symbiont zooxanthellae and/or decrease
      in their pigments. Since the algal symbionts provide the energy basis for corals
      and whole reefs, their loss or impairment of function leads to widespread
      mortality. This phenomenon has been documented numerous times in recent years,
      and has extensively damaged coral reefs all over the world. Temperature has been
      found to be the major cause of bleaching, and rising sea temperatures have
      increased the frequency of these catastrophic episodes. To characterize the
      response of zooxanthellae to temperature stress at the molecular level, we used
      the mRNA differential display technique to monitor changes in the abundance of
      specific mRNA species in the cell under different temperature conditions.
      Axenically grown zooxanthellae were exposed to a range of temperatures (21.7, 17,
      26 degrees C) before extraction of their mRNA. Of numerous differentially
      expressed sequences, seven mRNA species were amplified by the polymerase chain
      reaction (PCR) and sequenced. One of those sequences was positively identified as
      encoding a multifunction cell surface aminopeptidase, dipeptidyl peptidase IV,
      which is active in cell matrix adhesion. Our work illustrates the power of the
      differential display technique as a useful tool to study the response of
      zooxanthellae to stressors.

PMID- 16614871
TI  - Efficient transfection strategy for the spatiotemporal control of gene expression
      in zebrafish.
AB  - Functional analyses of gene function by knockdown and expression approaches
      strongly enhance the genetic study of development. In vivo application of the
      introduction of inhibitors of gene expression, mRNA, and expression constructs in
      the target region make it possible to perform region- and stage-specific
      regulation of gene function in a simple manner. As a basic tool for the
      conditional regulation of gene expression in target tissue, we present methods
      for the efficient introduction of antisense morpholino oligonucleotide (MO),
      mRNA, and expression plasmid constructs into early and later stage zebrafish
      embryo and larva. Lipofection of a neuron-specific expression construct plasmid
      encoding green fluorescent protein (GFP) into optic vesicle resulted in clear GFP
      expression in the retinotectal pathway in hatched larva. Co-lipofection of MO and
      GFP mRNA to the presumptive head region resulted in brain-specific knockdown of
      the gene in mid-stage embryos.

PMID- 16614873
TI  - Completion lymphadenectomy for melanoma patients with a positive sentinel node
      biopsy remains standard of care.

PMID- 16614874
TI  - Patient satisfaction: an increasingly important measure of quality.

PMID- 16614875
TI  - Trends in hospital and surgeon volume and operative mortality for cancer surgery.
AB  - BACKGROUND: We measured 13-year trends in operative mortality for six cancer
      resections. We then examined whether these trends are driven by changes in
      hospital and surgeon volume or by changes that occurred among all providers,
      regardless of volume. METHODS: We analyzed administrative discharge data on
      patients who received one of six cancer resections in Florida, New Jersey, and
      New York for three time periods: 1988 to 1991, 1992 to 1996, and 1997 to 2000.
      Descriptive statistics and nested regression models were used to test for changes
      in the association between inpatient mortality and annual hospital and annual
      surgeon volume over time, adjusting for patient and hospital characteristics.
      RESULTS: Unadjusted inpatient mortality rates for the six cancer resections
      declined between .8 and 4.0 percentage points between the time periods 1988 to
      1991 and 1997 to 2000. Over this time period, annual hospital and surgeon volumes
      for the six cancer operations increased an average of 24.3% and 24.2%,
      respectively. The logistic regressions indicated a relatively stable relationship
      over time between both increased hospital and surgeon volume and lower inpatient
      mortality. Simulations suggest that increases in hospital and surgeon procedure
      volume over time led to a reduction in inpatient mortality ranging from .1
      percentage points for rectal cancer to 2.3 percentage points for pneumonectomy.
      CONCLUSIONS: Persistence of the volume-outcome relation and increasing hospital
      and surgeon volumes explain much of the decline over time in inpatient mortality
      for five of the six cancer operations studied. Concentrating cancer resections
      among high-volume providers should lead to further reduced inpatient mortality.

PMID- 16614876
TI  - Improved outcome of resection of hilar cholangiocarcinoma (Klatskin tumor).
AB  - BACKGROUND: Treatment of hilar cholangiocarcinoma (Klatskin tumors) has changed
      in many aspects. A more extensive surgical approach, as proposed by Japanese
      surgeons, has been applied in our center over the last 5 years; it combines hilar
      resection with partial hepatectomy for most tumors. The aim of this study was to
      assess the outcome of a 15-year evolution in the surgical treatment of Klatskin
      tumors. METHODS: A total of 99 consecutive patients underwent resection for hilar
      cholangiocarcinoma in three 5-year time periods: periods 1 (1988-1993; n=45), 2
      (1993-1998; n=25), and 3 (1998-2003; n=29). Outcome was evaluated by assessment
      of completeness of resection, postoperative morbidity and mortality, and
      survival. RESULTS: The proportion of margin negative resections increased
      significantly from 13% in period 1 to 59% in period 3 (P<.05). Two-year survival
      increased significantly from 33%+/-7% and 39%+/-10% in periods 1 and 2 to 60%+/
      11% in period 3 (P<.05). Postoperative morbidity and mortality were considerable
      but did not increase with this changed surgical strategy (68% and 10%,
      respectively, in period 3). Lymph node metastasis was, next to period of
      resection, also associated with survival in univariate analysis. CONCLUSIONS:
      Mainly in the last 5-year period (1998-2003), when the Japanese surgical approach
      was followed, more hilar resections were combined with partial liver resections
      that included segments 1 and 4, thus leading to more R0 resections. This,
      together with a decrease in lymph node metastases, resulted in improved survival
      without significantly affecting postoperative morbidity or mortality.

PMID- 16614877
TI  - Implication of the BRCA2 and putative "BRCA3" genes in Dukes' stage C,
      replication error-negative colon cancer.
AB  - BACKGROUND: Although BRCA genes have been implicated in certain tumors,
      particularly breast tumors, their role in colon tumorigenesis has not been fully
      explored. We aimed to investigate the association of the BRCA2 and putative
      "BRCA3" genes in a homogeneous series of right-sided colon cancer specimens.
      METHODS: Twenty-three Dukes' stage C, replication error-negative carcinomas were
      selected from patients with right-sided colon cancer. After histological
      examination and microdissection, DNA was extracted from normal colon and
      carcinoma from each patient. Five microsatellite markers spanning the region of
      BRCA2 and BRCA3 on chromosome 13 (D13S218, D13S219, D13S165, D13S156, and
      D13S160) and two markers intragenic to BRCA2 and BRCA3 (D13S171 and D13S1308,
      respectively) were used. Polymerase chain reaction products were analyzed by
      using a fluorescent allele imbalance assay. RESULTS: Markers demonstrating the
      highest allelic imbalance were D13S1308 (53%), D13S171 (33%), and D13S160 (37%).
      CONCLUSIONS: The intragenic markers D13S1308 (BRCA3) and D13S171 (BRCA2) on
      chromosome 13 demonstrated a high frequency of allelic imbalance in primary colon
      carcinoma. This suggests an involvement of BRCA2 and putative BRCA3 in colon
      tumorigenesis in right-sided, replication error-negative, Dukes' stage C cancers.
      Further studies are needed to confirm the precise role of these genes, and any
      prognostic significance, in colon cancer.

PMID- 16614878
TI  - Effect of primary tumor extirpation in breast cancer patients who present with
      stage IV disease and an intact primary tumor.
AB  - BACKGROUND: Currently, therapy for breast cancer patients with stage IV disease
      and an intact primary tumor is metastasis directed; the primary tumor is treated
      only when it causes symptoms. A recent review suggested that surgery may improve
      long-term survival in such patients. We evaluated the effect of surgery in such
      patients on long-term survival and disease progression. METHODS: We reviewed the
      records of all breast cancer patients treated at our institution between 1997 and
      2002 who presented with stage IV disease and an intact primary tumor. Information
      collected included demographics, tumor characteristics, site(s) of metastases,
      type/date of operation, use of radiotherapy, chemotherapy and hormonal therapy,
      disease progression (time to progression and location of progression) in the
      first year after diagnosis, and last follow-up. Overall and metastatic
      progression-free survival were compared between surgery and nonsurgery patients.
      RESULTS: Of 224 patients identified, 82 (37%) underwent surgical extirpation of
      the primary tumor (segmental mastectomy in 39 [48%] and mastectomy in 43 [52%]),
      and 142 (63%) were treated without surgery. The median follow-up time was 32.1
      months. After adjustment for other covariates, surgery was associated with a
      trend toward improvement in overall survival (P=.12; relative risk, .50; 95%
      confidence interval, .21-1.19) and a significant improvement in metastatic
      progression-free survival (P=.0007; relative risk, .54; 95% confidence interval,
      .38-.77). CONCLUSIONS: Removal of the intact primary tumor for breast cancer
      patients with synchronous stage IV disease is associated with improvement in
      metastatic progression-free survival. Prospective studies are needed to validate
      these findings.

PMID- 16614879
TI  - Tumor bed boost omission after negative re-excision in breast-conservation
      treatment.
AB  - BACKGROUND: We evaluated the necessity of a tumor bed boost after whole-breast
      radiotherapy for early-stage breast cancer after breast-conserving surgery and
      negative re-excision. METHODS: Of patients treated at the Virginia Commonwealth
      and Tufts Universities with breast-conservation therapy for early-stage breast
      cancer between 1983 and 1999, 205 required re-excision of the tumor cavity to
      obtain clear margins and were found to be without residual disease. Adjuvant
      conventionally fractionated whole-breast radiotherapy was given to a total dose
      of 50 Gy in 25 fractions. The tumor bed boost was omitted. RESULTS: The median
      follow-up was 98 months (range, 6-229 months). The tumor histological diagnosis
      was primarily infiltrating ductal carcinoma (183 cases; 89%). Nodal involvement
      was documented in 49 cases (24%). There were four documented recurrences at the
      tumor bed site. Five in-breast recurrences were documented to be in a location
      removed from the tumor bed. The overall Kaplan-Meier 15-year in-breast control
      rate was 92.4%, and the freedom from true recurrence rate was 97.6%. CONCLUSIONS:
      The findings support the concept that postlumpectomy radiotherapy can be tailored
      according to the degree of surgical resection. There is an easily identifiable
      subgroup of patients who can avoid a tumor bed boost, thus resulting in a reduced
      treatment time and improved cosmesis, while maintaining local control rates that
      approach 100%. The data suggest that in patients who undergo a negative re
      excision, treatment with whole-breast radiotherapy to 50 Gy is a sufficient dose
      to maximally reduce the risk of local recurrence.

PMID- 16614880
TI  - Current issues in adjuvant treatment of stage II colon cancer.
AB  - BACKGROUND: Adjuvant chemotherapy with 5-fluorouracil modulated by folinic acid,
      combined with oxaliplatin, has now become an accepted standard of care for
      patients with stage III colon cancer. In contrast, the use of adjuvant therapy
      for stage II patients remains controversial, and the identification of reliable
      prognostic factors to aid therapeutic decision making is crucial. METHODS: The
      authors critically review the results of clinical trials and meta-analyses
      investigating the value of adjuvant chemotherapy for stage II patients,
      emphasizing the heterogeneous nature of this population and the difficulty of
      performing clinical trials with sufficient power to reliably assess treatment
      efficacy. They also discuss the evidence concerning potential prognostic factors,
      particularly molecular markers. RESULTS: Available clinical trial data do not
      support the routine use of adjuvant chemotherapy for all stage II patients but
      suggest that it should be considered, particularly for certain high-risk
      patients. Recent guidelines advocate considering factors such as tumor
      differentiation, tumor perforation, number of lymph nodes examined, and T stage
      when assessing the likely benefit:risk ratio. Microsatellite instability and
      allelic imbalance seem to be strong predictors of good and poor prognosis,
      respectively, and in the near future, therapeutic decision-making models are
      likely to be further refined by the inclusion of such molecular markers.
      CONCLUSIONS: There is growing evidence that the prognosis of certain stage II
      patients with unfavorable prognostic factors can be improved by adjuvant
      chemotherapy, and increasingly refined tools are now available to define those
      most likely to benefit. Referral of stage II patients for individual assessment
      is strongly recommended.

PMID- 16614881
TI  - Fine-needle aspiration optimizes surgical management in patients with thyroid
      cancer.
AB  - BACKGROUND: Fine-needle aspiration (FNA) is accurate in diagnosing papillary,
      medullary, and anaplastic thyroid cancer, as well as lymphoma. Although many
      surgeons routinely perform FNA before surgery, some question whether FNA
      influences operative management. Therefore, to determine whether FNA affects
      surgical management in patients with thyroid cancer, we reviewed our experience.
      METHODS: A total of 442 consecutive patients underwent thyroid surgery at 1
      academic center. Of these, 411 had surgery for an index nodule in the absence of
      previous radiation or familial thyroid cancer. FNA, operative, and permanent
      histology findings were reviewed. RESULTS: The average patient age was 46 years,
      and 79% were female. A total of 211 patients (51%) had a preoperative FNA, and 71
      (17%) had a final diagnosis of cancer. The sensitivity and specificity of FNA for
      thyroid cancer were 89% and 92%, respectively. In the FNA group, 1 (2.4%) of 41
      patients with papillary thyroid cancer required completion thyroidectomy. In
      contrast, in the no-FNA group, 4 (40%) of 10 patients with papillary thyroid
      cancer required a second operation. No patient in the FNA group received thyroid
      resection for lymphoma, whereas three (100%) of three patients with lymphoma in
      the no-FNA group were treated surgically. A total of 98% of the FNA group,
      compared with 54% of the no-FNA group, received optimal surgical treatment for
      thyroid cancer. CONCLUSIONS: FNA is a sensitive and specific test for the
      diagnosis of thyroid cancer, allowing definitive initial surgery and avoiding
      unnecessary procedures. Therefore, we recommend routine use of preoperative
      thyroid FNA, even in those patients in whom a resection is already planned.

PMID- 16614882
TI  - Satisfaction with care: an independent outcome measure in surgical oncology.
AB  - BACKGROUND: Outcomes for treatment for upper gastrointestinal cancer
      traditionally include procedure-related morbidity and mortality and long-term
      survival. Patient-reported outcomes, such as quality of life (QOL) and
      satisfaction measures, add to standard end points, but associations between these
      factors are not fully understood. This study examined how patient satisfaction
      related to surgical morbidity, treatment type, and QOL outcomes after inpatient
      treatment for upper gastrointestinal cancer. METHODS: Consecutive patients who
      had completed treatment in one unit were invited to participate in this study and
      complete the European Organization for Research and Treatment of Cancer QLQ
      PATSAT32 and QLQ-C30 questionnaires within 2 months of discharge. Regression
      analyses examined relationships between satisfaction and surgical morbidity
      (major complications and type of treatment) and between satisfaction and QOL
      variables, adjusting for age and sex. RESULTS: During the study, 181 patients
      were treated, 162 were eligible, and 139 returned both questionnaires (response
      rate, 86%). Of the study sample, the treatment outcome was potential cure in 105
      (67 esophagectomy and 38 D2 gastrectomy), and 34 received palliative treatment.
      Thirty-seven patients (27%) had major complications. Patients who received
      palliative treatment reported satisfaction and QOL scores similar to those of
      patients who received curative treatment. However, patients who experienced major
      morbidity reported significantly worse QOL than those without morbidity (P<.01).
      Satisfaction scores were the same in patients with or without complications.
      There were no associations between satisfaction and QOL scores (r<.34).
      CONCLUSIONS: Patient satisfaction with hospital care is independent of morbidity,
      treatment type, and QOL outcomes. It may be used to feed back information to
      providers of health care to improve patients' experiences of treatment.

PMID- 16614883
TI  - The surgeon-patient interaction in older women with breast cancer: what are the
      determinants of a helpful discussion?
AB  - BACKGROUND: Surgery is a key modality in the treatment of breast cancer. The
      patient-physician interaction is a key determinant of a range of outcomes, but
      there is little work examining the surgeon-breast cancer patient interaction. We
      analyzed data from 240 women with a new breast cancer diagnosis to better
      understand this interaction and to delineate the patient, surgeon, and surgeon
      patient interaction-level characteristics affecting this interaction. METHODS: A
      cross-sectional survey was conducted in Los Angeles County of 240 women with a
      new breast cancer diagnosis aged>or=55 years. Women were asked to rate on a scale
      of 0 to 10 how helpful overall the way their surgeon discussed their breast
      cancer with them was. Logistic regression models were constructed to assess the
      relationship of patient, surgeon, and surgeon-patient interaction characteristics
      to the outcome variable. RESULTS: Forty-four percent of women said that they
      found the way their surgeon discussed their breast cancer with them extremely
      helpful. Women with a higher level of perceived self-efficacy, a longer
      consultation time with the surgeon, a higher interactive information-giving
      score, and a higher participatory decision-making score had significantly higher
      odds of reporting the discussion to be "extremely helpful." CONCLUSIONS: Our
      results indicate that strategies to improve the patient's perceived self-efficacy
      (preparing questions beforehand, practicing, watching a role model, and so on)
      will improve the surgeon-patient discussion. At a systems level, adequate time
      should be budgeted for the consultation, and we must ensure that adequate
      communication skills are imparted to surgeons during their educational training.

PMID- 16614885
TI  - Prognostic score in gastric cancer: the importance of a conjoint analysis of
      clinical, pathologic, and therapeutic factors.
AB  - BACKGROUND: This study was designed to establish a prognostic score for gastric
      cancer that takes into account factors related to the tumor, the patient, and the
      treatment. METHODS: Two hundred thirty patients with gastric adenocarcinoma
      admitted t o the Department of Abdominal Surgery at Hospital do Cancer A. C.
      Camargo (Sao Paulo) and treated by gastrectomy from January 1992 until December
      1996 were included in this retrospective cohort. The prognostic score was created
      according to the variables identified in the multivariate analysis and by using
      the regression coefficients generated by the Cox regression. RESULTS: The 5-year
      overall survival rate was 44.5%. The final multivariate model identified six
      variables with a significant and independent effect on survival: sex, weight
      loss, lymphocyte count, tumor-node-metastasis staging, lymphadenectomy, and lymph
      node ratio. Patients were divided into four groups according to their scores, as
      follows: group 1, 0 to 3.0; group 2, 3.5 to 5.5; group 3, 6.0 to 8.5; and group
      4, 9.0 to 14.0. The 5-year survival rates were 91.5%, 49.3%, 20.3%, and .0% for
      the score groups 1, 2, 3, and 4, respectively (P<.001). The score was superior in
      the assessment of prognosis when compared with tumor-node-metastasis staging
      alone. CONCLUSIONS: It is possible to create a prognostic score that
      simultaneously includes factors related to the tumor, patient, and treatment,
      thus generating a more effective system in predicting the prognosis than the
      morphology-based staging systems.

PMID- 16614884
TI  - Prognostic significance of epidermal growth factor receptor expression in colon
      cancer patients undergoing curative surgery.
AB  - BACKGROUND: To investigate the role of epidermal growth factor receptor (EGFR)
      expression as a prognostic marker for prediction of cancer behavior and clinical
      outcomes in colon cancer patients undergoing potentially curative surgery.
      METHODS: EGFR determination using a commercially available immunohistochemistry
      kit was performed in tissues from 149 colon cancer patients receiving primary
      surgical treatment and in 25 normal colon mucosa specimens from noncancer
      patients. EGFR positivity was correlated in univariate and multivariate analyses
      with disease recurrence and survival. In addition, p27, p53, and vascular
      endothelial growth factor expression were assessed by immunohistochemistry in 104
      patients and correlated with EGFR tumor expression and clinical outcome. RESULTS:
      EGFR expression was detected in approximately one third of colon cancer patients
      (53 of 149; 35.6%). In 126 curatively treated patients, EGFR expression was
      correlated with disease recurrence and worse survival in both univariate and
      multivariate analyses. In a multivariate model for predicting recurrence and
      survival, Dukes' staging, p27, and EGFR expression were the only independent
      covariates. In particular, in Dukes' A and B patients the 5-year survival
      probability was 96% for EGFR-negative and high p27 expression cases and was 30.7%
      for EGFR-positive and low p27 expression cases. CONCLUSIONS: EGFR expression was
      an independent prognostic indicator of disease recurrence and poor survival in
      colon cancer patients undergoing curative surgery. In the context of novel
      therapeutic options such as molecularly targeted therapies, these findings
      suggest that anti-EGFR drugs could be evaluated in the adjuvant treatment of EGFR
      positive colon cancer patients.

PMID- 16614886
TI  - Quality of life after hyperthermic isolated limb perfusion for locally advanced
      extremity soft tissue sarcoma.
AB  - BACKGROUND: Quality of life (QoL) and posttraumatic stress symptoms (PTSS) were
      studied in patients with soft tissue sarcoma (STS) of the extremities treated
      with isolated limb perfusion and delayed resection, with or without adjuvant
      irradiation. METHODS: Forty-one patients received a questionnaire that included
      the RAND-36 and Impact of Event Scale. RESULTS: Thirty-nine STS survivors (16
      [41%] male and 23 [59%] female; median age, 59 years; range, 15-78 years)
      participated in the questionnaire survey (response rate, 95%). The median age at
      perfusion was 49 years (range, 14-72 years). No significant differences were
      found in mean scores between STS survivors and the reference group with the
      exception of a worse physical functioning. Patients with amputations showed
      significantly worse physical and social functioning and more role limitations
      than patients whose limbs were saved. Eleven patients (28%) had a PTSS score of
      0, and eight patients (20.5%) had a score>or=26, which suggested the need for
      psychological counseling. None of these eight patients had lost a limb. Patients
      who indicated that the choice of treatment was made by the surgeon rather than
      collaboratively showed significantly decreased social functioning, more role
      limitations, and intrusion. Greater treatment satisfaction was significantly
      related to better social functioning, more vitality, better general health
      perception, less intrusion, avoidance, and total Impact of Event Scale scores.
      CONCLUSIONS: Even though STS survivors' QoL was different from that of a
      reference group only in physical functioning, one fifth of the patients had PTSS.
      An amputation, the physician's decision rather than the patient's decision for
      the perfusion treatment and a low satisfaction with the performed treatment
      negatively influenced QoL.

PMID- 16614887
TI  - Expression of interleukin 11 and its receptor and their prognostic value in human
      breast cancer.
AB  - BACKGROUND: Recent experimental evidence has shown a potential role of
      interleukin (IL)-11 and its receptor in breast cancer development and
      progression. However, there is little clinical information to support this
      hypothesis. We examined the expression of IL-11 and its receptor in primary
      breast cancer tissue samples and correlated their level of expression with the
      clinical outcome. METHODS: Primary breast cancer samples (n=109) and matched
      background tissue obtained from patients in the cohort (n=33) were processed for
      frozen section and RNA extraction. Frozen sections from matched tissues were
      immunostained with IL-11 and IL-11 receptor antibodies. Staining intensity was
      analyzed by computer image analysis. RNA was reverse-transcribed and quantified
      before analysis by quantitative polymerase chain reaction. Results were expressed
      as the number of transcripts (standardized by beta-actin). The data were compared
      with the clinical outcome of the disease. RESULTS: The intensity of staining for
      both IL-11 and the IL-11 receptor was distinctly high in tumor samples (P<.01).
      The transcript level of IL-11 was significantly higher in node-positive tumor
      samples compared with node-negative samples (P=.02). Tumors with a poor
      prognostic index and poor histological grade showed a higher level of IL-11. A
      higher level of IL-11 was linked to poorer survival with Kaplan-Meier survival
      analysis. CONCLUSIONS: IL-11 can be a predictor of poor prognosis in human breast
      cancer.

PMID- 16614888
TI  - Cell growth and shikonin production of Arnebia euchroma in a periodically
      submerged airlift bioreactor.
AB  - Arnebia euchroma was grown in a 2-l periodically submerged, airlift bioreactor
      (PSAB) in which the non-submerged (immobilization culture) and submerged
      (suspension culture) operations were controlled automatically. PSAB had
      advantages in improving cell growth, shikonin content, shikonin production and
      cell aggregation compared with suspension culture. Under the optimal
      submerged/non-submerged period of 10 min/15 h, the shikonin content (4.6%, w/w)
      and, cell dry mass (16.8 g/l) were 229 and 26% higher than those in suspension
      culture.

PMID- 16614889
TI  - Enhanced methane production from anaerobic digestion of disintegrated and
      deproteinized excess sludge.
AB  - To improve biogas yield and methane content in anaerobic digestion of excess
      sludge from the wastewater treatment plant, the sludge was disintegrated by using
      various methods (sonication, alkaline and thermal treatments). Since
      disintegrated sludge contains a high concentration of soluble proteins, the
      resulting metabolite, ammonia, may inhibit methane generation. Therefore, the
      effects of protein removal from disintegrated sludge on methane production were
      also studied. As a result, an obvious enhancement of biogas generation was
      observed by digesting disintegrated sludge (biogas yield increased from 15 to 36
      ml/g COD(added).day for the raw excess sludge and the sonicated sludge,
      respectively). The quality of biogas was also improved by removing proteins from
      the disintegrated sludge. About 50% (w/w) of soluble proteins were removed from
      the suspension of disintegrated sludge by salting out using 35 g MgCl(2) x
      6H(2)O/l and also by isoelectric point precipitation at pH 3.3. For deproteinized
      sludge, methane production increased by 19%, and its yield increased from 145
      ml/g COD(removed) to 325 ml/g COD(removed). Therefore, the yield and quality of
      biogas produced from digestion of excess sludge can be enhanced by disintegrating
      the sludge and subsequent protein removal.

PMID- 16614890
TI  - A polysaccharide isolated from the medicinal herb Bletilla striata induces
      endothelial cells proliferation and vascular endothelial growth factor expression
      in vitro.
AB  - A polysaccharide from the traditional Chinese medicinal herb, Bletilla striata
      (Thunb.) Reichb. f., was isolated, purified and characterized. It induced the
      proliferation of human umbilical vascular endothelial cells and the expression of
      vascular endothelial growth factor up to 156% and 147% of control after 72 h,
      respectively.

PMID- 16614891
TI  - Functional characterization of ketoreductase (rubN6) and aminotransferase (rubN4)
      genes in the gene cluster of Streptomyces achromogenes var. rubradiris.
AB  - ORF's for rubN6 and rubN4 have been annotated as thymidine diphosphate glucose 4
      ketoreductase and thymidine diphosphate glucose 3-aminotransferase by sequence
      analysis of the rubradirin biosynthetic gene cluster cloned from Streptomyces
      achromogenes var. rubradiris NRRL 3061. Both ORFs were heterologously expressed
      in Escherichia coli as His-tagged fusion proteins. The functionalities of TDP
      glucose 4-ketoreductase and TDP-glucose 3-aminotransferase were verified by in
      vitro enzyme assay, and a biosynthetic pathway for TDP-D: -rubranitrose is
      proposed.

PMID- 16614892
TI  - Co-lyophilization with D-proline greatly enhances peroxidase's stereoselectivity
      in a non-aqueous medium.
AB  - The impact of co-lyophilizing horseradish peroxidase (HRP) with numerous amino
      acids and other chiral excipients on the enzyme's subsequent stereoselectivity
      [E(S/R)] in the sulfoxidation of thioanisole in 2-propanol was systematically
      investigated. While many improved the stereoselectivity of (and significantly
      activated) HRP, the greatest effect was observed with D-proline which enhanced
      the E(S/R) value by over an order of magnitude from synthetically meaningless to
      useful.

PMID- 16614893
TI  - Direct electrochemical immunoassay based on immobilization of protein-magnetic
      nanoparticle composites on to magnetic electrode surfaces by sterically enhanced
      magnetic field force.
AB  - A direct electrochemical immunoassay system based on the immobilization of alpha
      1-fetoprotein antibody (anti-AFP), as a model system, on the surface of core
      shell Fe(2)O(3)/Au magnetic nanoparticles (MNP) has been demonstrated. To
      fabricate such an assay system, anti-AFP was initially covalently immobilized on
      to the surface of core-shell Fe(2)O(3)/Au MNP. Anti-AFP-modified MNP (bio
      nanoparticles) were then attached to the surface of carbon paste electrode with
      the aid of a permanent magnet. The performance and factors influencing the
      performance of the resulting immunosensor were studied. alpha-1-Fetoprotein
      antigen was directly determined by the change in current or potential before and
      after the antigen-antibody reaction versus saturated calomel electrode. The
      electrochemical immunoassay system reached 95% of steady-state potential within 2
      min and had a sensitivity of 25.8 mV. The linear range for AFP determination was
      from 1 to 80 ng AFP ml(-1) with a detection limit of 0.5 ng AFP ml(-1). Moreover,
      the direct electrochemical immunoassay system, based on a functional MNP, can be
      developed further for DNA sensor and enzyme biosensor.

PMID- 16614894
TI  - Improvement of interfacial protein stability by CHAPS.
AB  - Emulsification of aqueous protein solutions in methylene chloride triggered the
      formation of water-insoluble aggregates at a water/methylene chloride interface.
      As a result, the amounts of beta-lactoglobulin and ovalbumin recovered in water
      were 36 and 44%, respectively. Addition of 5 mM: CHAPS in the aqueous phase
      raised the degree of beta-lactoglobulin recovery to 96%. Sodium taurocholate,
      however, failed to improve protein recovery. The stabilizing effect of CHAPS was
      also protein-specific and concentration-dependent: at >or=5 mM: , the surfactant
      caused unfolding of ovalbumin to make a water-soluble oligomer. CHAPS thus
      stabilizes proteins at an interface.

PMID- 16614895
TI  - Production of the artemisinin precursor amorpha-4,11-diene by engineered
      Saccharomyces cerevisiae.
AB  - The gene encoding for amorpha-4,11-diene synthase from Artemisia annua was
      transformed into yeast Saccharomyces cerevisiae in two fundamentally different
      ways. First, the gene was subcloned into the galactose-inducible, high-copy
      number yeast expression vector pYeDP60 and used to transform the Saccharomyces
      cerevisiae strain CEN.PK113-5D. Secondly, amorpha-4,11-diene synthase gene,
      regulated by the same promoter, was introduced into the yeast genome by
      homologous recombination. In protein extracts from galactose-induced yeast cells,
      a higher activity was observed for yeast expressing the enzyme from the plasmid.
      The genome-transformed yeast grows at the same rate as wild-type yeast while
      plasmid-carrying yeast grows somewhat slower than the wild-type yeast. The
      plasmid and genome-transformed yeasts produced 600 and 100 microg/l of the
      artemisinin precursor amorpha-4,11-diene, respectively, during 16-days' batch
      cultivation.

PMID- 16614896
TI  - Enzymatic synthesis of cinnamic acid derivatives.
AB  - Using Novozym 435 as catalyst, the syntheses of ethyl ferulate (EF) from ferulic
      acid (4-hydroxy 3-methoxy cinnamic acid) and ethanol, and octyl methoxycinnamate
      (OMC) from p-methoxycinnamic acid and 2-ethyl hexanol were successfully carried
      out in this study. A conversion of 87% was obtained within 2 days at 75 degrees C
      for the synthesis of EF. For the synthesis of OMC at 80 degrees C, 90% conversion
      can be obtained within 1 day. The use of solvent and high reaction temperature
      resulted in better conversion for the synthesis of cinnamic acid derivatives.
      Some cinnamic acid esters could also be obtained with higher conversion and
      shorter reaction times in comparison to other methods reported in the literature.
      The enzyme can be reused several times before significant activity loss was
      observed.

PMID- 16614897
TI  - Extraction of high quality of RNA and construction of a suppression subtractive
      hybridization (SSH) library from chestnut rose (Rosa roxburghii Tratt).
AB  - Chestnut rose (Rosa roxburghii Tratt) is a rare fruit crop of promising
      economical importance in fruit and ornamental exploitation in China. Isolation of
      high quality RNA from chestnut rose is difficult due to its high levels of
      polyphenols, polysaccharides and other compounds, but a modified CTAB extraction
      procedure without phenol gave satisfactory results. High concentrations of PVP
      (2%, w/v), CTAB (2%, w/v) and beta-mercaptoethanol (4%, v/v) were used in the
      extraction buffer to improve RNA quality. The average yield was about 200 microg
      RNA g(-1) fresh leaves. The isolated RNA was of sufficient quality for
      construction of suppression subtraction hybridization (SSH) library, which
      allowed the isolation of several pathogen-induced defense genes.

PMID- 16614898
TI  - Expression of poplar chitinase in tomato leads to inhibition of development in
      colorado potato beetle.
AB  - The previously described poplar chitinase, WIN6, is induced during infestation by
      gypsy moth (Lymantria dispar L.) larvae, thus suggesting a role in defense
      against insect pests. To test this hypothesis, we produced tomato seedlings
      infected with a recombinant potato virus X (PVX), which produces WIN6, and tested
      its insecticidal properties on Colorado potato beetle [CPB; Leptinotarsa
      decemlineata (Say)], which is a serious pest of tomatoes and other crops. The
      advantage of PVX is that plant material is ready for insect bioassay within 3-4
      weeks of constructing the recombinant virus. Considering that production of
      transgenic tomato seedlings using Agrobacterium takes at least 6 months, this
      hastens the rate at which genes can be examined. Upon insect bioassay, only 47%
      CPB neonates feeding on leaves containing >0.3% w/w WIN6 developed to 2nd instar
      while 93% of controls reached 2nd instar. To our knowledge this is the first
      plant chitinase that retards development of an insect pest.

PMID- 16614899
TI  - Determination of conductivity of bacteria by using cross-flow filtration.
AB  - An important property of the bacterial surface is its conductivity. To obtain
      reliable conductivity values, it is essential to handle the cells as gently as
      possible during the measurement procedure. We have developed a method where a
      standard conductivity meter is used in combination with cross-flow filtration,
      thus avoiding repeated centrifugation and resuspension. With this method, the
      conductivity of Bacillus subtilis was determined to be 7,000 microS/cm, which is
      a deviation from previously published data by almost an order of a magnitude.

PMID- 16614901
TI  - Gene cloning and heterologous expression of glycoside hydrolase family 55 beta
      1,3-glucanase from the basidiomycete Phanerochaete chrysosporium.
AB  - The basidiomycete Phanerochaete chrysosporium produces several beta-1,3
      glucanases when grown on laminarin, a beta-1,3/1,6-glucan, as the sole carbon
      source. To characterize one of the major unknown beta-1, 3-glucanases with a
      molecular mass of 83 kDa, identification, cloning, and heterologous over
      expression were carried out using the total genomic information of P.
      chrysosporium. The cDNA encoding this enzyme included an ORF of 2337 bp and the
      deduced amino acid sequence contains a predicted signal peptide of 26 amino acids
      and the mature protein of 752 amino acids. The amino acid sequence showed a
      significant similarity with glycoside hydrolase family 55 enzymes from
      filamentous fungi and was named Lam55A. Since the recombinant Lam55A expressed in
      the methylotrophic yeast Pichia pastoris degraded branched beta-1,3/1,6-glucan as
      well as linear beta-1,3-glucan, the kinetic features of the enzyme were compared
      with those of other beta-1,3-glucanases.

PMID- 16614902
TI  - Generation of recombinant Chinese hamster ovary cell lines by microinjection.
AB  - Microinjection is a gene transfer technique enabling partial control of plasmid
      delivery into the nucleus or cytoplasm of cultured animal cells. Here this method
      was used to establish various recombinant mammalian cell lines. The injection
      volume was estimated by fluorescence quantification of injected fluorescein
      isothyocynate (FITC)-dextran. The DNA concentration and injection pressure were
      then optimized for microinjection into the nucleus or cytoplasm using a reporter
      plasmid encoding the green fluorescent protein (GFP). Nuclear microinjection was
      more sensitive to changes in these two parameters than was cytoplasmic
      microinjection. Under optimal conditions, 80-90% of the cells were GFP-positive 1
      day after microinjection into the nucleus or the cytoplasm. Recombinant cell
      lines were recovered following microinjection or calcium phosphate transfection
      and analyzed for the level and stability of recombinant protein production. In
      general, the efficiency of recovery of recombinant cell lines and the stability
      of reporter protein expression over time were higher following microinjection as
      compared to CaPi transfection. The results demonstrate the feasibility of using
      microinjection as a method to generate recombinant cell lines.

PMID- 16614903
TI  - A novel PHB depolymerase from a thermophilic Streptomyces sp.
AB  - A novel PHB depolymerase from a thermophilic Streptomyces sp. MG was purified to
      homogeneity by hydrophobic interaction chromatography and gel filtration. The
      molecular mass of the purified enzyme was 43 kDa as determined by size exclusion
      chromatography and 41 kDa by SDS-PAGE. The optimum pH and temperature were 8.5
      and 60 degrees C respectively. The enzyme was stable at 50 degrees C and from pH
      6.5-8.5. The enzyme hydrolyzed not only bacterial polyesters, i.e. poly(3
      hydroxybutyric acid and poly(3-hydroxybutyrate-co-3-hydroxyvalerate), but also
      synthetic, aliphatic polyesters such as polypropiolactone, poly(ethylene adipate)
      and poly(ethylene succinate).

PMID- 16614904
TI  - Differential gene expression of human CD34+ hematopoietic stem and progenitor
      cells before and after culture.
AB  - Ex vivo expanded CD34+ hematopoietic stem and progenitor cells (HSPCs) have
      compromised homing and engraftment capacities. To investigate underlying
      mechanisms for functional changes of expanded HSPCs, we compared gene expression
      profiling of cultured and fresh CD34+ cells derived from cord blood using SMART
      PCR and cDNA array: 20 genes were up-regulated while 25 genes were down-regulated
      in cultured CD34+ HSPCs. These differentially expressed genes are involved
      primarily in proliferation, differentiation, apoptosis, and homing.

PMID- 16614905
TI  - Equilibrium yields of mono- and di-lauroyl mannoses through lipase-catalyzed
      condensation in acetone in the presence of molecular sieves.
AB  - Modification was made to our previously reported method to predict the
      equilibrium yields for the synthesis of mono- and di-lauroyl mannoses through the
      lipase-catalyzed condensation of lauric acid and mannose in acetone in the
      presence of molecular sieves. HPLC and mass spectra (MS) analyses indicated that
      two types of dilauroyl mannoses, which would be positional isomers of each other
      and are designated dilauroyl mannose I and II, were produced as well as
      monolauroyl mannose. The predicted yields of total mannose esters and dilauroyl
      mannose I agreed well with the experimental ones on the whole. The equilibrium
      yields of dilauroyl mannose II were higher than the predicted values, while the
      experimental values of monolauroyl mannose were lower than the predicted values.

PMID- 16614906
TI  - Cloning, expression, and characterization of a DNA ligase from a
      hyperthermophilic archaeon Thermococcus sp.
AB  - Genomic analysis of a hyperthermophilic archaeon, Thermococcus sp. NA1, revealed
      an ORF of 1689 bases encoding 562 amino acids that showed a high similarity to
      DNA ligases from other hyperthermophilic archaea. The ligase, which was
      designated TNA1_lig (Thermococcus sp. NA1 ligase), was cloned and expressed in
      Escherichia coli. The recombinant TNA1_lig was purified by metal affinity
      chromatography. The optimum ligase activity of the recombinant TNA1_lig occurred
      at 80 degrees C and pH 7.5. The enzyme was activated by MgCl2 and ZnCl2 but was
      inhibited by MnCl2 and NiCl2. Additionally, the enzyme was activated by either
      ATP or NAD+.

PMID- 16614907
TI  - Characterization of pbpA and pbp2 encoding penicillin-binding proteins located on
      the downstream of clavulanic acid gene cluster in Streptomyces clavuligerus.
AB  - Two genes, pbpA (orf18) and pbp2 (orf19) located on the downstream of clavulanic
      acid (CA) gene cluster of Streptomyces clavuligerus were cloned into pET-28a(+),
      and confirmed to encode a family of high molecular-weight penicillin-binding
      proteins (PBPs). Both genes were amplified from genomic DNA by PCR and expressed
      in E. coli BL21 (DE3). Hydropathy plots of the proteins revealed a single stretch
      of hydrophobic amino acids indicating them to be transmembrane proteins. Pbp2 had
      lower affinity to penicillin G compared to PbpA, and was essential to the cell
      growth in contrast to PbpA.

PMID- 16614908
TI  - Heterochromatin protein 1 deleted chromo domain decreases gene silencing of
      transgene in mouse.
AB  - The heterochromatin protein 1 (HP1) regulates epigenetic gene silencing by
      promoting and maintaining chromatin condensation. To decrease gene silencing, the
      chromo domain (CD) in the M31 (the main HP1 in mouse) was deleted by site
      directed mutagenesis. Vector pcDNA3.1(+)/M31-DeltaCD, in which the M31-DeltaCD is
      driven by the CMV promoter, and vector pcDNA3.1(+)/P1A3-M31-DeltaCD, in which the
      M31-DeltaCD is driven by a goat ss-casein promoter were constructed. The former
      vector was transfected into a murine fibroblast cell line, which can express
      enhanced green fluorescent protein (EGFP). EGFP expression, which was determined
      by flow cytometric analysis, increased approximately 80% in the transfected
      cells. After injection of the latter vector into transgenic mouse mammary glands,
      which can express human clotting factor IX (hFIX), the hFIX expression level in
      the mouse milk increased approximately 40-60% and hFIX in one mouse milk was
      maintained at a high concentration for over 10 days.

PMID- 16614909
TI  - Polycyclic aromatic hydrocarbon (PAH) degradation coupled to methanogenesis.
AB  - Baltimore Harbor (Baltimore, MD) sediments were utilized to initiate anaerobic
      enrichment cultures with polycyclic aromatic hydrocarbons (PAHs) in the absence
      of supplementary electron acceptors. Cultures amended with naphthalene and
      phenanthrene exhibited sustained, transferable degradation of the PAHs.
      Bromoethanesulfonic acid, a selective inhibitor of methanogenesis, inhibited the
      degradation of 200 microM: naphthalene and phenanthrene; molecular
      characterization based on 16S rRNA sequences confirmed that methanogenic Archaea
      were eliminated, thus providing evidence that methanogenesis is involved in the
      degradation pathway.

PMID- 16614910
TI  - Rheology and shear stress of Centaurea calcitrapa cell suspension cultures grown
      in bioreactor.
AB  - Centaurea calcitrapa suspension cultures were grown either in Erlenmeyer flasks
      or in a mechanically stirred bioreactor. Its rheological behaviour, when fitted
      to the Oswald-de Waele model (power law), showed pseudoplastic characteristics in
      both cases. The flow behaviour index (n) decreased over the course of a growth
      cycle and the consistency index (K) increased, reached a value of 1.81 N sn m(-2
      )run on 2 l bioreactor. Bioreactor cultivation of C. calcitrapa cells at
      different agitation rates (30, 60, 100 and 250 rpm), highlighted the influence of
      shear forces on cell viability loss (90-34%) and phenol accumulation (74-140
      microg l(-1)), due to increased stirring speeds. Analysis of these results
      suggests that this cell line is shear-sensitive. An empirical exponential
      correlation was defined between apparent viscosity and biomass concentration,
      under the studied conditions, giving the possibility to estimate the prevailing
      broth regime and to optimize bioreactor design.

PMID- 16614911
TI  - Anti-apoptotic activity of laminarin polysaccharides and their enzymatically
      hydrolyzed oligosaccharides from Laminaria japonica.
AB  - Laminarin polysaccharides (LP1) were prepared from Laminaria japonica, a marine
      brown alga with potential biological activities, by hot water extraction,
      ultrafiltration and gel chromatography; the molecular weights of the LP1s were
      between 5 and 10 kDa. Laminarin oligosaccharides (LO) derived by hydrolyzing LP1
      with an endo-beta-(1-->3)-glucanase from Bacillus circulans were mainly di- and
      penta-oligosaccharides. Treatment of mouse thymocytes with LO or LP1 (1-4 mg ml(
      1)) suppressed apoptotic death around 3- or 2-fold and extended cell survival in
      culture at a rate of about 30 or 20%. A mouse cDNA microarray showing the genes
      coding for immune response proteins were induced and apoptotic cell death
      proteins were reduced significantly by LO provided preliminary information
      regarding the immunomodulatory mechanism of LO. These results suggest that
      laminarin oligosaccharides and polysaccharides can be utilized to develop new
      immunopotentiating substances and functional alternative medicines.

PMID- 16614912
TI  - New group-specific 16S rDNA primers for monitoring foaming mycolata during saline
      waste-water treatment.
AB  - Newly designed group-specific PCR primers for denaturing gradient gel
      electrophoresis (DGGE) were used to investigate foaming mycolata from a
      bioreactor treating an industrial saline waste-water. Genetic profiles on DGGE
      gels were different with NaCl at 1.65 and 8.24 g l(-1), demonstrating that
      mycolata community was affected by salinity. A semi-nested PCR strategy resulted
      in more bands in community genetic profiles than direct amplification. DNA
      sequencing of bands confirmed the efficacy of the novel primers with sequences
      recovered being most similar to foam producing mycolata. The new group-specific
      primers/DGGE approach is a new step toward a more complete understanding of
      functionally important groups of bacteria involved in biological treatment of
      waste-water.

PMID- 16614914
TI  - Dual reporter genes enabling cell tracing with viable and reliable selection of
      various cell types.
AB  - Dual reporter genes driven by either a ubiquitous cytomegalovirus (CMV) or a
      neuro-specific tubulin alpha1 promoter (Talpha1) were constructed. The new genes,
      CMV (pCMV-GL) or Talpha1 promoter-driven GFP-LacZ (pTalpha1-GL), robustly
      expressed the fused GFP-LacZ protein reporting constitutive expressions in
      various cell types including CHO cells, loach and chicken embryos, and neuro
      specific expression in differentiating mouse embryonic stem cells, respectively.
      The dual reporter genes thus provide a versatile tool for the studies of gene
      expression, cell lineage within the embryo and possibly the fate of stem cells in
      transplantation experiment, thus facilitating different analyses depending on the
      experimental purposes.

PMID- 16614915
TI  - Enhancement of enantioselectivity in the Bacillus subtilis protease-catalyzed
      hydrolysis of N-free amino acid esters using the ester grouping-modification
      approach.
AB  - The generality of enantioselectivity enhancement through the modification of the
      alcohol moiety of a substrate ester was ascertained, for in the Bacillus subtilis
      protease-catalyzed hydrolysis of N-unprotected amino acid esters the
      enantioselectivity was enhanced largely by switching the conventional methyl
      ester to esters with a longer alkyl chain such as the isobutyl ester (from E = 3
      to E = 130-170 in the case of 4-fluorophenylalanine esters) as in the enzymatic
      hydrolysis mediated by Aspergillus oryzae protease. There was indeed a profound
      dependence of E on the nature of the ester grouping.

PMID- 16614916
TI  - One-step purification and immobilization in cellulose of the GroEL apical domain
      fused to a carbohydrate-binding module and its use in protein refolding.
AB  - The apical domain of the chaperonin, GroEL, fused to the carbohydrate binding
      module type II, CBD(Cex), of Cellulomonas fimi, was expressed in Escherichia
      coli. The recombinant protein, soluble or from inclusion bodies, was directly
      purified and immobilized in microcrystalline cellulose particles or cellulose
      fabric membranes. Assisted refolding of rhodanese by the immobilized mini
      chaperone showed a two-fold improvement as compared to a control. Using
      chromatographic refolding, 35% of rhodanese activity was recovered in only 5 min
      (mean residence time) as compared to 17% for spontaneous refolding. This mini
      chaperone immobilized in cellulose could be a cost-efficient method to refold
      recombinant proteins expressed as inclusion bodies.

PMID- 16614917
TI  - Cloning and sequence analysis of the gene encoding (6-4)photolyase from
      Dunaliella salina.
AB  - DNA photolyase can repair UV-induced DNA damage in a light-dependent manner. A
      cDNA of (6-4)photolyase from Dunaliella salina (GenBank accession number:
      AY845324) was cloned, sequenced and its amino acid sequence was deduced. The
      derived amino acid sequence showed high homology with other (6-4)photolyases and
      a predicted 3D model was constructed by homology modeling.

PMID- 16614918
TI  - Improvement of Bacillus thuringiensis delta-endotoxins synthesis yields through
      acquisition of erythromycin resistance.
AB  - The acquisition of the erythromycin resistance by Bacillus thuringiensis kurstaki
      improved yields of delta-endotoxins in sporulating cells ranging from 134 to
      215%. Resistance to erythromycin decreased the final spore count by at least 50%.
      Consequently, erythromycin resistance is an efficient tool for the improvement of
      bioinsecticides yields with a high ratio of delta-endotoxins to spores.

PMID- 16614919
TI  - The occurrence of antibiotic resistance genes in Taq polymerases and a
      decontamination method applied to the detection of genetically modified crops.
AB  - Different antibiotic resistance (AR) genes, such as Bla, Tet and NPTII,
      contaminate commercially available Taq polymerases. The specificity of the AR
      gene PCR can be increased when using a restriction enzyme-based decontamination
      of polymerase. The elimination of Taq polymerase contamination allows the use of
      PCR tests to screen seeds (corn) and processed food for the presence of
      genetically modified organisms (GMO) based on the detection of AR genes. Without
      a decontamination procedure for AR genes, PCR screening tests should be
      interpreted with caution.

PMID- 16614920
TI  - Flavonoid-3',5'-hydroxylase from Phalaenopsis: a novel member of cytochrome
      P450s, its cDNA cloning, endogenous expression and molecular modeling.
AB  - A novel cDNA for the flavonoid-3',5'-hydroxylase (F35H) gene was cloned from
      petals of Phalaenopsis, and designated as Phf35h (accession number DQ148458 in
      GenBank/EMBL/DDBJ). The genomic clone of Phf35h was isolated by a PCR-based
      strategy. Nucleotide sequence analysis revealed that its genomic clone contains
      one intron and an open reading frame encoding a polypeptide of 507 amino acid
      residues. Southern hybridization analysis indicated the presence of a single gene
      coding for Phf35h. RT-PCR analysis showed that the Phf35h mRNA is transcribed in
      late phase of petal development, which is concomitant with the appearance of
      anthocyanins in petal tissue. The transcript is abundant in the purple petals but
      not in leaves or roots. The three-dimensional model of PhF3'5'H protein is
      classified into an alpha-domain which contains most of the alpha-helices with
      three small beta-sheets, a beta-domain that contains the larger beta-sheets with
      three small alpha-helices by homology modeling. The substrate-binding site for
      dihydrokaempferol on PhF3'5'H protein was determined by molecular docking
      algorithm. A highly conserved HPPTPLSLPH sequence was predicted to contact the
      aromatic ring of dihydrokaempferol.

PMID- 16614921
TI  - Kinetic analysis of the ex vivo expansion of human hematopoietic stem/progenitor
      cells.
AB  - The total cell expansion of human umbilical cord blood (CB) and adult bone marrow
      (BM) CD34+-enriched cells cultured in supplemented serum-free media, either over
      irradiated human feeder layers or in stroma-free systems, were characterized by a
      simple kinetic model using only two parameters: the specific cell expansion rate,
      mu, and the death rate constant, k(k). Both CB and BM cells can expand at
      approximately the same rate (0.21 day(-1)) in this culture system however, cell
      death depends on the presence of stroma and the environment in which the cells
      are cultured.

PMID- 16614922
TI  - Presence of unintended Agrobacterium tumefaciens cloning vector sequences in
      genetically modified plants.
AB  - Agrobacterium transformation was used in the production of genetically modified
      plants from oilseed rape (Brassica napus) and tobacco (Nicotiana tabacum). After
      inoculation stop with the antibiotic timentin, a subsequent one-week treatment
      eliminated the vector bacterium from the oilseed rape plate explant cultures.
      From the tobacco, however, we recorded vector-derived signals one week after
      potting the regenerants in the greenhouse and still 10 weeks later. Genetically
      modified plants produced through Agrobacterium-transformation therefore cannot be
      guaranteed to be completely free of unintended vector sequences after antibiotic
      treatment.

PMID- 16614923
TI  - High-level expression of an alpha-L-arabinofuranosidase from Thermotoga maritima
      in Escherichia coli for the production of xylobiose from xylan.
AB  - To efficiently produce xylobiose from xylan, high-level expression of an alpha-L
      arabinofuranosidase gene from Thermotoga maritima was carried out in Escherichia
      coli. A 1.5-kb DNA fragment, coding for an alpha-L-arabinofuranosidase of T.
      maritima, was inserted into plasmid pET-20b without the pelB signal sequence
      leader, and produced pET-20b-araA1 with 8 nt spacing between ATG and Shine
      Dalgarno sequence. A maximum activity of 12 U mg(-1) was obtained from cellular
      extract of E. coli BL21-CodonPlus (DE3)-RIL harboring pET-20b-araA1. The over
      expressed alpha-L-arabinofuranosidase was purified 13-fold with a 94% yield from
      the cellular extract of E. coli by a simple heat treatment. Production of
      xylooligosaccharides from corncob xylan by endoxylanase and alpha-L
      arabinofuranosidase was examined by TLC and HPLC: xylobiose was the major product
      from xylan at 90 degrees C and its proportion in the xylan hydrolyzates increased
      with the reaction time. Hydrolysis with in the xylanase absence of alpha-L
      arabinofuranosidase gave only half this yield.

PMID- 16614924
TI  - Cloning and production of a novel bacteriocin, lactococcin K, from Lactococcus
      lactis subsp. lactis MY23.
AB  - A gene encoding the antimicrobial peptide, lactococcin K, was isolated from
      Lactococcus lactis subsp. lactis MY23 then cloned and expressed in Escherichia
      coli. Because the expressed lactococcin K was formed as an inclusion body in
      recombinant E. coli, a fusion protein containing lactococcin K and maltose
      binding protein (MBP) was produced in a soluble form. For high-level production
      of lactococcin K, we performed a pH-stat fed-batch culture to produce 43,000 AU
      lactococcin K ml(-1) in 12 h.

PMID- 16614926
TI  - A comparative investigation on different refolding strategies of recombinant
      human tissue-type plasminogen activator derivative.
AB  - Recombinant human tissue-type plasminogen activator derivative (r-PA), fused with
      thioredoxin (Trx), was expressed in Escherichia coli. The resultant fusion
      protein, Trx-r-PA, was almost completely in the form of inclusion bodies and
      without activity. Different refolding strategies were investigated including
      different post-treatment of solubilized Trx-r-PA inclusion bodies, on-column
      refolding by size-exclusion chromatography (SEC) using three gel types (Sephacryl
      S-200, S-300 and S-400), refolding by Sephacryl S-200 with a urea gradient and
      two-stage temperature control in refolding. An optimized on-column refolding
      process for Trx-r-PA inclusion bodies was established. The collected Trx-r-PA
      inclusion bodies were dissolved in 6 M: guanidine hydrochloride (Gdm.HCl), and
      the denatured protein was separated from dithiothreitol (DTT) and Gdm.HCl with a
      G25 column and simultaneously dissolved in 8 M: urea containing oxidized
      glutathione (GSSG). Finally a refolding of Trx-r-PA protein on Sephacryl S-200
      column with a decreasing urea gradient combined with two-stage temperature
      control was employed, and the activity recovery of refolded protein was increased
      from 3.6 to 13.8% in comparison with the usual dilution refolding.

PMID- 16614927
TI  - Growth of Escherichia coli, Pichia pastoris and Bacillus cereus in the presence
      of the ionic liquids [BMIM][BF4] and [BMIM][PF6] and Organic Solvents.
AB  - The influence of the two most commonly used ionic liquids (1-butyl-3-methyl
      imidazolium tetrafluoroborate, [BMIM][BF(4)], 1-butyl-3-methyl imidazolium
      hexafluorophosphate, [BMIM][PF(6)]) and three selected organic solvents
      (dimethylsulfoxide, ethanol, methanol) on the growth of Escherichia coli, Pichia
      pastoris and Bacillus cereus was investigated. [BMIM][BF(4)] was toxic at 1%
      (v/v) on all three microorganisms. The minimal inhibitory concentration (MIC) of
      [BMIM][BF(4)] on E. coli growth was between 0.7 and 1% (v/v). In contrast,
      [BMIM][PF(6)] was less toxic for P. pastoris and B. cereus, whereas E. coli was
      not able to tolerate [BMIM][PF(6)] (MIC value: 0.3-0.7% v/v). Growth of P.
      pastoris was unaffected by [BMIM][PF(6)] at 10% (v/v). Similar results were found
      for dimethylsulfoxide. Thus, ionic liquids (ILs) can have substantial inhibitory
      effects on the growth of microorganisms, which should be taken into account for
      environmental reasons as well as for the use of ILs as co-solvents in
      biotransformations.

PMID- 16614928
TI  - Creation of circularly permutated yellow fluorescent proteins using fluorescence
      screening and a tandem fusion template.
AB  - By experimenting with many different circularly permutated yellow fluorescent
      protein (cpYFP) variants as acceptors in fluorescence resonance energy transfer
      based biosensors, the optimal dynamic range can be discovered by sampling the
      possibilities of relative fluorophore orientations before and after bioactivity.
      Hence, to facilitate the sampling process, we introduced a new approach to
      construct a library of cpYFP variants using fluorescence screening and a tandem
      fusion template. This new approach is rapid because it does not require creating
      intermediate N- and C-terminal fragments and it allows quick screening for
      positive colonies by fluorescence. As a demonstration, eleven cpYFP variants were
      created and eight showed fluorescence. The emission and excitation spectra of
      these cpYFP variants showed strong similarity to YFP and therefore can be used in
      replacement.

PMID- 16614929
TI  - Lactose-induced production of human soluble B lymphocyte stimulator (hsBLyS) in
      E. coli with different culture strategies.
AB  - Over-production of human soluble B lymphocyte stimulator (hsBLyS) was carried out
      with four different fed-batch culture strategies using lactose as inducer,
      instead of IPTG, in a fed-batch culture of Escherichia coli. As lactose acted as
      both inducer and carbon source, the best and simplest culture strategy was direct
      feeding of lactose after batch culture, thereby giving hsBLyS at 3.7 g l(-1) and
      a productivity of 0.11 g l(-1) h(-1).

PMID- 16614930
TI  - Application of a novel oscillatory flow micro-bioreactor to the production of
      gamma-decalactone in a two immiscible liquid phase medium.
AB  - A novel micro-bioreactor based on the oscillatory flow technology was applied to
      the scale-down of the biotechnological production of gamma-decalactone. A
      decrease up to 50% of the time required to obtain the maximum concentration of
      the compound was observed, when compared with other scaled-down platforms
      (stirred tank bioreactor or shake flask). A three-fold increase in gamma
      decalactone productivity was obtained by increasing oscillatory mixing intensity
      from Re(o) approximately 482 to Re(o) approximately 1447. This was presumably
      related to the effective contribution of the reactor geometry to enhanced mass
      transfer rates between the two immiscible liquid phases involved in the process
      by increasing the interfacial area.

PMID- 16614931
TI  - Deciphering the importance of three key media components in human embryonic stem
      cell cultures.
AB  - Development of a serum free, feeder-free (SFFF) culture platform for human
      embryonic stem cells (hESC) will be important for the expansion of hESC for
      future cell therapy applications. However, currently, culture of hESC consists of
      a combination of basal media, basic fibroblast growth factor (bFGF), serum
      replacer (SR) and conditioned media (CM) from feeders, and it is unclear which
      components of the mixture are absolutely critical in the maintenance of hESC. To
      evaluate the relative contributions of these media components in the development
      of SFFF culture, each was systematically eliminated and pluripotency assayed by
      dual embryonic stem cell markers, Oct-4 and TRA-1-60. We concluded that SR was
      the most critical component in the platform, followed by bFGF and CM produced by
      feeders, where down-regulation of Oct-4 occurred after 2, 5 and 5 passages,
      respectively, upon their withdrawal from the complete media.

PMID- 16614932
TI  - Aluminium chloride enhances colchicine production in root cultures of Gloriosa
      superba.
AB  - Root cultures of Gloriosa superba were treated with 5 mM: methyl jasmonate and
      125 microM: AlCl3 which enhanced the intracellular colchicine content of the
      roots by 50-fold and 63-fold, respectively. Ten millimolar of CaCl2 and 1 mM:
      CdCl2 enhanced biomass significantly (7- to 8.6-fold, respectively) while maximum
      release of colchicine into the medium was obtained with 10 mM: CdCl2. Casein
      hydrolysate, yeast extract and silver nitrate had no significant effect on growth
      and colchicine accumulation in root cultures.

PMID- 16614933
TI  - Direct force measurement of the interaction between liposome and the C2A domain
      of synaptotagmin I using atomic force microscopy.
AB  - The binding force between a liposome and the C2A domain of synaptotagmin I was
      determined by an atomic force microscopy (AFM). Liposomes were immobilized on the
      surface of the L1 sensor chip and the C2A domains, which recognize
      phosphatidylserine, were chemically conjugated onto a gold-coated cantilever tip.
      The average interaction force between the C2A domain and the liposome was 306 (+/
      57) pN while the force between untreated cantilever and the liposome was 58 (+/
      16) pN. This work helps understand the physicochemical interactions between
      proteins and lipid vesicles for the design of high affinity protein probes
      against the apoptotic cell surface.

PMID- 16614934
TI  - A simple and green procedure for the microbial effective synthesis of 1
      phenylethyl alcohol in both enantiomeric forms.
AB  - Both R- and S-phenylethyl alcohol of high enantiomeric purity (98%) and with a
      satisfactory yield (40-80%) were obtained by bioreduction of acetophenone,
      catalyzed by whole cells of baker's yeast.

PMID- 16614935
TI  - CAGE displays oncogenic potential and induces cytolytic T lymphocyte activity.
AB  - The cancer associated gene (CAGE) is a novel cancer/testis antigen. Over
      expression of CAGE enhanced growth rates, promoted cell motility and led to an
      ROS scavenging effect which was accompanied by an induced catalase cavity.
      Further, peptides of CAGE induced cytolytic T lymphocytes (CTL) activity, and
      CD8+ T cells pre-sensitized with these peptides displayed cytotoxic effects
      against cancer cells expressing CAGE. These results suggest that CAGE would be a
      valuable target for the development of an anti-cancer vaccine.

PMID- 16614938
TI  - Processing unpointed Hebrew: what can we learn from determining the identicalness
      of monosyllabic and bisyllabic nouns.
AB  - The aim of this study was to determine whether Hebrew readers reference
      phonological information for the silent processing of unpointed Hebrew nouns. A
      research paradigm in which participants were required to perform consecutive
      same/different judgments regarding the identicalness of members of stimulus pairs
      was used for answering this question. Twenty-eight students (mean grade 4.9)
      participated in the study. The nouns used in preparing the word stimulus pairs
      were comprised of various amounts of syllabic information (monosyllabic versus
      bisyllabic) and differed in the degree this information was represented by their
      letter graphemes. The main findings suggest that the processing of the
      identicalness of unpointed Hebrew words may not involve the referencing of their
      phonological information.

PMID- 16614939
TI  - The research status of Clayman and Heritage's (2002) "The news interview".
AB  - The databases of three books with almost identical titles are examined in order
      to throw light on the theory of neutralistic professionalism of news interviewers
      and on the empirical logic of the most recent of the three: "The news interview"
      by Steven Clayman and John Heritage (2002). Instead of a theory of neutralism, a
      theory of perspectivity that applies to both interviewer and interviewee is
      presented. The logic of Clayman and Heritage's arguments is found wanting in a
      number of respects: (a) their treatment of TV and radio interviews as if they
      were identical; (b) their treatment of news interviews in the United States and
      Great Britain as essentially the same in practices and ground rules; (c) their
      inferences from isolated excerpts to the structure of the news interview itself;
      (d) their very concept of the news interview as "an interactional encounter
      between a journalist and one or more newsworthy public figures" (p. 1).
      Inaccuracies in their database make it unsatisfactory as support for a theory of
      neutralistic professionalism. Despite these limitations, Clayman and Heritage
      provide an excellent overview of the recent history of the news interview in the
      United States and Britain and a wealth of information about the local
      organization of news interviews.

PMID- 16614940
TI  - Foundation and practice of neurofeedback for the treatment of epilepsy.
AB  - This review provides an updated overview of the neurophysiological rationale,
      basic and clinical research literature, and current methods of practice
      pertaining to clinical neurofeedback. It is based on documented findings,
      rational theory, and the research and clinical experience of the authors. While
      considering general issues of physiology, learning principles, and methodology,
      it focuses on the treatment of epilepsy with sensorimotor rhythm (SMR) training,
      arguably the best established clinical application of EEG operant conditioning.
      The basic research literature provides ample data to support a very detailed
      model of the neural generation of SMR, as well as the most likely candidate
      mechanism underlying its efficacy in clinical treatment. Further, while more
      controlled clinical trials would be desirable, a respectable literature supports
      the clinical utility of this alternative treatment for epilepsy. However, the
      skilled practice of clinical neurofeedback requires a solid understanding of the
      neurophysiology underlying EEG oscillation, operant learning principles and
      mechanisms, as well as an in-depth appreciation of the ins and outs of the
      various hardware/software equipment options open to the practitioner. It is
      suggested that the best clinical practice includes the systematic mapping of
      quantitative multi-electrode EEG measures against a normative database before and
      after treatment to guide the choice of treatment strategy and document progress
      towards EEG normalization. We conclude that the research literature reviewed in
      this article justifies the assertion that neurofeedback treatment of
      epilepsy/seizure disorders constitutes a well-founded and viable alternative to
      anticonvulsant pharmacotherapy.

PMID- 16614941
TI  - Increased concentrations of transforming growth factor beta1 and beta2 in the
      plasma of patients with glioblastoma.
AB  - Recently, several in vitro studies have demonstrated production of the potent
      immunosuppressive cytokine transforming growth factor beta (TGF-beta)2 in
      glioblastoma cell lines. Systematic studies of the concentration of TGF-beta
      isoforms in the plasma of patients harboring intracerebral tumors do not exist.
      In the present study, the concentrations of TGF-beta1 and TGF-beta2 in platelet
      poor plasma of 21 patients with glioblastoma before and after extensive resection
      were measured by specific ELISA systems and related to survival. The plasma
      concentrations of latent TGF-beta1 of patients with glioblastoma prior to surgery
      were significantly higher in comparison to healthy control probands, but not to
      patients with multiple sclerosis (MS). Furthermore, latent TGF-beta2 was found to
      be significantly increased in the plasma of patients with glioblastoma in
      comparison to healthy control probands and patients with MS. After extensive
      resection of the tumor, the value of latent TGF-beta2 evidently decreased.
      Interestingly, the concentration of latent TGF-beta2 prior to surgery was
      correlated with survival and a strong relationship was found between the survival
      and the difference of latent TGF-beta2 levels prior to surgery minus the TGF
      beta2 concentrations 7 days after surgery. A higher difference in these plasma
      concentrations >6 ng/ml vs. <6 ng/ml clearly correlates with a longer survival
      time. In conclusion, this study suggests that glioblastoma does secret TGF-beta2
      in vivo and that TGF-beta2 may play an important role in glioblastoma patients.

PMID- 16614942
TI  - Spinal extramedullary anaplastic ependymoma with spinal and intracranial
      metastases.
AB  - We describe a 29-year-old woman who presented with progressive neck pain, sensory
      deficit and weakness in both arms. Magnetic resonance imaging (MRI) of the
      cervical spine revealed an extramedullary tumor with severe spinal cord
      compression. During surgery an intradural extramedullary tumor was found. Further
      imaging showed a second lumbar spinal tumor. Microscopy of both tumors showed
      that both tumors were anaplastic ependymomas, which almost never present as
      extramedullary tumors. Two years after surgery, an intracranial extracerebral
      metastasis was found, without evidence of spinal recurrence.

PMID- 16614943
TI  - Vinorelbine combined with a protracted course of temozolomide for recurrent brain
      metastases: a phase I trial.
AB  - Temozolomide (TMZ) has shown modest efficacy in the treatment of recurrent brain
      metastasis (BM). We designed a new regimen utilizing dose-intensified, protracted
      course of TMZ in combination with vinorelbine, a lipophilic large-spectrum agent,
      in an attempt to improve the efficacy of TMZ. This phase I study was conducted to
      establish the maximum tolerated dose (MTD) of vinorelbine for this combination.
      Patients with recurrent or progressive BM were eligible. Chemotherapy consisted
      of 28-day cycles with TMZ (150 mg/m2, days 1-7 and 15-21) and vinorelbine (days
      one and eight at escalating doses). The starting dose was 15 mg/m2, with
      increments of 5 mg/m2 for each cohort of 3-6 patients, until MTD was reached (30
      mg/m2). A total of 21 patients were enrolled; the median age was 59 (41-77). The
      primary tumor was lung cancer in 13 patients (NSCLC in 10, SCLC in 3), breast in
      6, renal in 1 and endometrial in 1. Vinorelbine dose was 15 mg/m2 in seven
      patients, 20 mg/m2 in five, 25 mg/m2 in four and 30 mg/m2 in six. Grades 3 and 4
      neutropenia developed in six patients, lymphopenia in nine, and thrombocytopenia
      in six; other toxicities were rare. No dose-limiting toxicity was seen. Out of 18
      evaluable patients 2 had a radiographic response (one partial and one minor).
      Disease was stable in 6 of 18 patients and the median survival was 27 weeks. This
      regimen was well tolerated and a phase II trial using a dose of 30 mg/m2 of
      vinorelbine is warranted.

PMID- 16614944
TI  - Loss of heterozygosity of the APC gene found in a single case of
      oligoastrocytoma.

PMID- 16614945
TI  - Incidence of infusion plan alterations after angiography in patients undergoing
      intra-arterial chemotherapy for brain tumors.
AB  - During intra-arterial (IA) chemotherapy of brain tumors, the initial vessels
      chosen for infusion are based on the vascular distribution of the tumor as
      revealed by CT or MR imaging. However, angiography may reveal details of vascular
      anatomy that require an alteration of the vessel infusion plan. The incidence of
      infusional alterations and the underlying vascular anatomy involved remains
      unknown in patients with brain tumors undergoing IA chemotherapy. To evaluate
      this question, we performed a chart, CT/MRI, and angiography review of brain
      tumor patients receiving IA chemotherapy. Seventy-eight patients were identified
      with primary (39) and metastatic (39) brain tumors. The cohort consisted of 40
      males and 38 females, with a mean age of 47.8 years. During the course of IA
      treatment, angiographic review identified 5 patients (6.4%) that required an
      alteration of the vessel infusion plan. In three cases, angiography demonstrated
      more substantial perfusion of the tumor from a different arterial supply. In two
      cases, angiography revealed variations in normal anatomy associated with
      unexpected tumor perfusion. Careful interpretation of angiography at the
      initiation of each cycle of IA chemotherapy is very important to verify that the
      appropriate vessels have been chosen for drug infusion, in order to maximize
      regional dose intensity. In our series, the angiography results necessitated an
      alteration of the infusion plan in 6.4% of the patient cohort.

PMID- 16614946
TI  - Gemistocytic astrocytomas: histomorphology, proliferative potential and genetic
      alterations--a study of 32 cases.
AB  - Gemistocytic astrocytomas (GAs) are a distinct variant of astrocytomas, generally
      classified as WHO grade II, and are associated with an aggressive biological
      behavior. This study was undertaken to determine the histomorphological spectrum,
      and correlate these with their proliferative potential and genetic alterations,
      in order to establish a biological basis for their unfavorable prognosis.A total
      of 32 GAs diagnosed during an 11-year period (1993-2003) were included in the
      study. Immunoreactivity for CD3 (T-cells), CD20 (B-cells) and CD68 (macrophages)
      were evaluated to characterize the perivascular inflammatory infiltrates, while
      p53, epidermal growth factor receptor (EGFR), cyclin D1 and p27-immunolabeling
      were studied to analyze the tumor biology.Overall, the mean gemistocytic index in
      the study was 39.6% (range, 12.2-80.8%), with multinucleation in gemistocytes and
      mitosis being present in 56.2% and 15.6% respectively. Perivascular mononuclear
      cell cuffing was seen in 56.2% cases, which was immunopositive for CD3 and CD68
      in 14 cases each, with 13 cases being immunopositive for both. Similar type of
      inflammatory infiltrates was also present within the tumor parenchyma.
      Proliferation index depicted by MIB-1 LI was low (mean: 3.7%; range: 0.5-10.5%),
      with 70% cases having LI of <5%. MIB-1 labeling was restricted to the small
      astrocytic cells, similar to p27 and cyclin D1 immunoreactivity, both of which
      were present in 71.5% cases. In contrast, p53 protein expression was present in
      75% cases, and was strongly positive in both gemistocytes and small cells,
      denoting neoplastic population. However, EGFR protein expression was consistently
      negative in all cases. Gemistocytes lack proliferative activity possibly
      indicating terminal differentiation, while small cells are the proliferating
      cells and their overall percentage may reflect the biological aggressiveness of
      these tumors and help to identify GAs of higher grade undergoing malignant
      progression. Therefore it appears that GAs should not be uniformly graded as
      grade II but should be subdivided into grades II and III neoplasms based on
      histological features and MIB-1 LI. The poor prognosis in GAs could be attributed
      both to the high frequency of p53 mutations and low p27 LI.

PMID- 16614947
TI  - Cytoplasmic, but not nuclear, p16 expression may signal poor prognosis in high
      grade astrocytomas.
AB  - BACKGROUND: The negative consequences of the cytoplasmic localization of p16 in
      patients with high-grade astrocytomas, on their prognosis, was investigated.
      METHODS: p16 Expression was examined in 20 anaplastic astrocytoma and 42
      glioblastoma patients by immunohistochemical analysis, and the relationship
      between both cytoplasmic and nuclear p16 expression and prognosis analyzed.
      RESULTS: The cytoplasmic expression of p16 statistically correlated with poor
      prognosis. On the other hand, no correlation was observed between p16 nuclear
      expression and patient survival. CONCLUSION: The cytoplasmic immunoreactivity of
      p16 appears to be an unfavorable prognostic indicator in high-grade astrocytoma
      patients. The localization of p16 expression should be determined when evaluating
      the prognosis of these patients.

PMID- 16614948
TI  - Impact of Ginkgo Biloba Extract EGb 761 on ischemia/reperfusion - induced
      oxidative stress products formation in rat forebrain.
AB  - Dysbalance in reactive oxygen/nitrogen species is involved in the pathogenesis of
      cerebral ischemia/reperfusion injury (IRI). Ginkgo biloba extract (Egb 761) pre
      treatment was used to observe potential antioxidant/neuroprotective effect after
      global ischemia/reperfusion. Egb 761 significantly decreased the level of
      lipoperoxidation (LPO) in rat forebrain total membrane fraction (homogenate)
      induced by in vitro oxidative stress (Fe(2+)+H(2)O(2)). In animals subjected to
      four-vessel global ischemia for 15 min and 2-24 h reperfusion the EGb
      pretreatment slightly decreased LPO in forebrain homogenate. However, as detected
      in EGb treated group, the LPO-induced lysine conjugates are attenuated in
      comparison to non-treated IRI animals. EGb significantly improved parameters
      which indicate forebrain protein oxidative damage after IRI. The intensity of
      tryptophane fluorescence was increased by the 18.2% comparing to non-treated IRI
      group and bityrosine fluorescence was significantly decreased in ischemic (21%)
      and 24 h reperfused (15.9%) group in comparison non-treated IRI group. In
      addition, the level of total free SH- groups in pre-treated animals was
      significantly higher comparing to non-treated animals. Our results indicate that
      extract of EGb 761 has potent antioxidant activity and could play a role to
      attenuate the IRI-induced oxidative protein modification and lipoperoxidation in
      the neuroprotective process.

PMID- 16614949
TI  - Omeprazole treatment ameliorates oxyntic atrophy induced by DMP-777.
AB  - Atrophic gastritis, characterized as parietal cell loss or oxyntic atrophy, is
      the primary event in the evolution of the spectrum of metaplastic and
      hyperplastic lineage changes thought to predispose to gastric neoplasia. A number
      of animal models have provided insights into the lineage changes induced by
      oxyntic atrophy. Recently, we have reported a model for pharmacological induction
      of oxyntic atrophy with DMP-777. DMP-777 ablates parietal cells selectively and
      leads to the gastric cell lineage changes including foveolar hyperplasia and
      spasmolytic polypeptide expressing metaplasia (SPEM). Previous investigations
      showed that DMP-777 dissipated a gastric tubulovesicle proton gradient without
      impairing the H/K-ATPase activity, consistent with its pharmacological action as
      a parietal cell-specific protonophore which could induce parietal cell necrosis
      through backwash of luminal acid into actively secreting cells. We hypothesized
      that, if DMP-777 was acting as a parietal cell protonophore, then suppression of
      acid secretion should protect parietal cells from the toxic effects of the drug.
      In this study, we pretreated and coadministered the proton pump inhibitor
      omeprazole with DMP-777 to determine the effect of active acid secretion
      inhibition on the DMP-777-induced histologic changes in the stomachs of male
      rats. Omeprazole pretreatment ameliorated DMP-777-induced parietal cell loss as
      well as foveolar hyperplasia. These results indicate that active acid secretion
      is required for DMP-777 cytotoxicity, consistent with its suggested behavior as a
      parietal cell-specific protonophore.

PMID- 16614950
TI  - Prevalence, sociodemography, and quality of life of older versus younger patients
      with irritable bowel syndrome: a population-based study.
AB  - We studied the prevalence as well as the sociodemographic characteristics and QOL
      of older adults (> 50 years) with irritable bowel syndrome (IBS) among the
      population at large and compared it to their younger counterparts'. We
      hypothesized that IBS is less prevalent among older persons and they suffer
      poorer QOL compared to younger IBS patients. A total of 1000 adults from nine
      sites, including a medical center, churches, and a blood bank in our metropolitan
      area (670 African Americans, 320 Caucasians, and 10 others), completed self
      administered questionnaires providing sociodemographic information and details
      regarding bowel habits and associated symptoms for diagnosing the IBS based on
      Rome II criteria. QOL was assessed by the SF-12 questionnaire. The study database
      was divided into two groups, younger (< 50 years) and older (> or = 50 years).
      The two age groups were similar with respect to gender and household income.
      Ninety-five of the 1000 participants had IBS, giving a total sample prevalence of
      9.5% (< 50 years, 9.9%, vs > or = 50 years, 7.6%). The prevalence of IBS was
      similar in the two groups irrespective of race, sex, marital status, size of
      household, location of residence (rural versus urban), level of educational
      status, and household income. Compared to the older group, there was a trend
      toward a higher prevalence of IBS among divorced subjects (12.7% vs 0%; P = 0.1)
      and those below poverty level of income (15.3% vs 7.5%; P = 0.09) in the younger
      subjects. In contrast, older IBS patients were more likely to attend church
      regularly (32.5% vs 58.8%; P < 0.05). There were no differences in history of
      traveler's diarrhea, food intolerance, and drug allergies between the two groups.
      Health care utilization was similar between the two IBS groups in terms of number
      of physician visits, use of prescription and alternative medications, and being
      disabled due to IBS. There was no difference in the overall QOL score means (27.8
      vs 29.5; P = NS) or in its general health and physical functioning components.
      However, older IBS patients had better social functioning (9.1 vs 9.8; P < 0.05).
      Although in our study IBS occurred less frequently among older adults than among
      younger patients, the difference is not statistically significant. While IBS
      affects QOL at all ages, social functioning was actually better on average among
      older compared to younger IBS patients.

PMID- 16614951
TI  - Prevalence of irritable bowel syndrome and depression in fibromyalgia.
AB  - The purpose of this study was to determine the point prevalence of depressive
      symptoms, using the PRIME-MD questionnaire, and irritable bowel syndrome (IBS),
      while comparing the Rome II to the Rome I criteria, in patients with fibromyalgia
      (FM) and rheumatologic controls in an outpatient setting. The prevalence of IBS
      in FM patients (n = 105) was 63% by Rome I and 81% by Rome II criteria. The
      prevalence of IBS in controls (n = 62) was 15% by Rome I and 24% by Rome II
      criteria (FM vs. control; P < 0.001). Depressive symptoms were met in 40% of FM
      patients and 8% of controls (P < 0.001). The coexistence of IBS and depressive
      symptoms in the FM patients was 31% (Rome I) and 34% (Rome II). The prevalence of
      IBS and depressive symptoms was higher in FM patients compared to the control
      population. Identification of IBS and depressive symptoms in FM patients might
      enable clinicians to better meet the needs of this patient population.

PMID- 16614952
TI  - Transient lactose malabsorption in patients affected by symptomatic uncomplicated
      diverticular disease of the colon.
AB  - Lactose malabsorption (LM) may be secondary to several small bowel diseases, and
      small intestinal overgrowth (SIBO) may be one of them. We looked for a
      correlation between symptomatic diverticular disease of the colon and LM and
      assessed whether this correlation may be related to SIBO. Ninety consecutive
      patients (pts; 39 males, 51 females; mean age, 67.2 years; range, 32-91 years)
      affected by symptomatic uncomplicated diverticular disease of the colon were
      evaluated to assess orocecal transit time (OCTT), SIBO, and LM by lactulose and
      lactose H2 breath test (H2-BT) at entry and after 8 weeks of treatment. OCTT was
      delayed in 67 of 90 pts (74.44%). Fifty-three of 90 pts (58.88%) showed SIBO, and
      OCTT was normal in 23 of 90 pts (25.56%). LM was diagnosed in 59 of 90 pts
      (65.55%): 49 of 59 (71.74%) were simultaneously affected by SIBO and delayed OCTT
      (and thus 49 of 53 pts [92.45%] with delayed OCTT and SIBO were affected by LM);
      3 of 59 pts (5.09%) showed only delayed OCTT; 7 of 59 pts (11.86%) did not show
      either SIBO or delayed OCTT. The association of LM and SIBO was statistically
      significant (P < 0.001). Seventy-nine of 86 pts (91.86%) showed normal OCTT,
      while OCTT remained prolonged but shorter in the remaining 7 pts (8.14%). SIBO
      was eradicated in all pts completing the study, while a new lactulose H2-BT
      showed persistence of SIBO in one pt with recurrence of symptomatic diverticular
      disease. Forty-seven of 59 pts (79.66%) had a normal lactose H2-BT (P < 0.002),
      while 12 of 59 pts (20.34%) showed persistence of LM. LM disappeared in 46 of 49
      pts (93.88%) concurrently with normalization of OCTT and eradication of SIBO (P <
      0.002); it also disappeared in 1 of 3 pts (33.33%) previously affected by delayed
      OCTT (without SIBO) and LM concurrently with normalization of OCTT. On the
      contrary, it persisted in all pts with normal OCTT and absence of SIBO. Moreover,
      it persisted also in the pt with recurrence of symptomatic diverticular disease
      and persistence of SIBO. In conclusion, most pts affected by symptomatic
      uncomplicated diverticular disease of the colon showed LM, and in more than 70%
      of cases it disappeared after successful treatment of the colonic disease.

PMID- 16614953
TI  - Mild whole-body heat stress alters retinoid metabolism in the rat small
      intestine.
AB  - Mild heat treatment can modulate metabolism and prevent stress-induced
      alterations in cells and tissues. Retinoids are known to influence cellular
      metabolism and are essential for growth and differentiation, particularly of
      epithelial tissue. This study examines the effect of mild heat treatment on
      retinoid alterations in enterocytes in the rat small intestine. Heat treatment
      changed the differentiation pattern of enterocytes along the villus-crypt axis,
      accompanied by increases in retinol, retinaldehyde, and retinoic acid in
      proliferating crypt cells. Activities of retinoid metabolizing enzymes such as
      retinaldehyde oxidase and retinaldehyde reductase were also increased. These
      results suggest that mild heat treatment can alter retinoid metabolism in the
      small intestine, which might influence epithelial cell proliferation and
      differentiation.

PMID- 16614954
TI  - Oral rush desensitization in peanut allergy: a case report.

PMID- 16614955
TI  - Prevalence of methylenetetrahydrofolate reductase polymorphisms in young patients
      with inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) has been related to mutations of
      methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in the metabolism
      of folate and methionine, both of which are important factors in DNA methylation
      and synthesis. A mutated MTHFR genotype was associated with increased toxicity of
      methotrexate treatment. The objective of this study was to verify, in a
      population of young patients with IBD, the presence of an association among
      mutations in the MTHFR gene, the incidence of IBD, and the risk of adverse events
      during the treatment with thiopurines azathioprine (AZA) or 6-mercaptopurine
      (6MP). Ninety-two patients with IBD were enrolled; 63 were treated with
      thiopurines; patients and 130 controls were genotyped for MTHFR mutations by PCR
      based methods. The incidence of mutations in the MTHFR gene was not different
      between patients with IBD and control subjects; the mutated genotype was not
      associated with an increased risk of toxicity during thiopurine treatment.

PMID- 16614956
TI  - Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid
      induced colitis in rats.
AB  - The aim of this study was to assess the efficiency of hyperbaric oxygen alone and
      in combination with 5-aminosalicylic acid in the acetic acid-induced colitis
      model, a well-known experimental model of inflammatory bowel disease in rats.
      Rats were randomly divided into five groups. In the noncolitis control group,
      rats were given isotonic saline, while in the other groups rats were treated by
      intracolonic administration of 4% acetic acid. In group 2, the untreated control
      group, no additional therapy was applied. In groups 3, 4, and 5 hyperbaric
      oxygen, 5-aminosalicylic acid. and 5-aminosalicylic acid + hyperbaric oxygen
      therapies were applied, respectively. Administration of acetic acid caused an
      inflammatory response in all animals. Histopathologic score was significantly
      higher in group 2 than in any other group. 5-Aminosalicylic acid and hyperbaric
      oxygen significantly decreased the histopathologic score (P < 0.05).
      Myeloperoxidase activity was also reduced significantly by 5-aminosalicylic acid
      (P < 0.05) but not by hyperbaric oxygen. The most prominent ameliorative effect,
      however, was seen in group 5 and the histopathologic score and myeloperoxidase
      activity were significantly lower than in groups 3 (P < 0.05) and 4 (P < 0.001).
      Hydroxyproline level also increased significantly in group 5, but not in groups 3
      and 4 (P < 0.001). These findings indicate that hyperbaric oxygen therapy is
      effective in reducing the extent of colitis induced by acetic acid, although it
      is not as potent as 5-aminosalicylic acid. The combination of hyperbaric oxygen
      and 5-aminosalicylic acid, however, led to a much more prominent reduction in the
      severity of colitis. Hyperbaric oxygen may have a promising place in the
      treatment of inflammatory bowel disease.

PMID- 16614958
TI  - Intestinal 5-hydroxytryptamine and mast cell infiltration in rat experimental
      colitis.
AB  - The present study evaluated the extent of dysfunction of the 5
      hydroxytryptaminergic system in inflamed (distal colon) and noninflamed segments
      (jejunum and ileum) after intrarectal administration of 2,4,6-trinitrobenzene
      sulfonic acid (TNBS) in the rat. Dexamethasone was administered to control rats
      and TNBS-treated animals before and for 7 days after TNBS treatment. Tissue
      levels of 5-hydroxytryptamine (5-HT) in the inflamed colon were higher than in
      controls. The density of mast cells was also markedly increased. Treatment with
      dexamethasone attenuated the inflammatory response but did not prevent the
      increase in colonic 5-HT. In the noninflamed jejunum and terminal ileum, 5-HT
      tissue levels were markedly increased, but treatment with dexamethasone prevented
      this increase. It is concluded that the increase in 5-HT levels in the inflamed
      colon in TNBS-induced colitis may result from mast cell infiltration. In the
      noninflamed intestine, 5-HT tissue levels were also increased, favoring the view
      of a generalized mast cell infiltration.

PMID- 16614957
TI  - Effects of L-carnitine on oxidant/antioxidant status in acetic acid-induced
      colitis.
AB  - Recently, the role of oxidative stress in the pathogenesis of ulcerative colitis
      has been investigated. This study was designed to evaluate the possible
      beneficial effects of L-carnitine on tissue injury and oxidative stress in acetic
      acid-induced colitis in rats. Acetic acid administration induced severe damage
      macroscopically and histopathologically in colon and significantly increased the
      levels of malondialdehyde and myeloperoxidase in colonic tissue. Supplementation
      of L-carnitine to acetic acid-treated rats did not prove to induce any
      improvements in macroscopic scores, while L-carnitine administration improved
      histopathologic scores and significantly decreased malondialdehyde and
      myeloperoxidase levels in treatment groups. Acetic acid administration
      significantly decreased reduced glutathione, superoxide dismutase, and catalase
      levels in colonic homogenate. Supplementation of L-carnitine prevented the
      depletion of reduced glutathione levels but significantly increased superoxide
      dismutase levels. On the other hand, no significant change in catalase activity
      was observed. In conclusion, these results may reflect that L-carnitine could be
      beneficial as a complementary agent in treatment of ulcerative colitis.

PMID- 16614959
TI  - Colonic electrical stimulation regulates colonic transit via the nitrergic
      pathway in rats.
AB  - Gastrointestinal electrical stimulation has been proposed for the treatment of
      gastrointestinal motor disorders. However, little is known about potential roles
      of colonic electrical stimulation (CES). The aim of this study was to evaluate
      the effect and mechanism of CES on colonic transit in conscious rats. Male rats
      (N = 14) were equipped with a pair of colonic serosal electrodes for stimulation
      and a catheter in the colon. Colonic transit was assessed in four randomized
      sessions with or without CES and with or without nitric oxide synthesis blocker,
      L-NNA, by calculating the output of phenol red from the anus every 10 min for 90
      min. Results were as follows. (1) CES with trains of short pulses significantly
      enhanced colonic transit. Colonic emptying was 57.3 +/- 6.1% in the control
      session and 81.9 +/- 4.6% with CES at 90 min, reflecting a 43% increase. (2) L
      NNA delayed colonic transit compared with saline and prevented the accelerative
      effect of CES on colonic transit. We conclude that CES has an excitatory effect
      on colonic transit and this excitatory effect may be mediated via the nitrergic
      pathway.

PMID- 16614960
TI  - Regional variations in neurokinin receptor subtype contributions to muscularis
      mucosae and epithelial function in rat colon.
AB  - It is known that the muscularis mucosae and mucosa are not pharmacologically
      homogeneous throughout the rat colon. The aim of this study was to simultaneously
      characterize all three neurokinin (NK) receptors in the muscularis mucosae and
      mucosa along the length of the rat colon. Strips of proximal, mid, and distal
      colonic muscularis mucosae were prepared for isometric recording or sheets of
      muscle-free mucosa were mounted in Ussing chambers for measurement of short
      circuit current. In both muscularis mucosae and mucosa the greatest responses to
      substance P were found in the proximal region. Use of selective agonists revealed
      the presence of all three NK receptors in both structures, however, selective
      antagonism suggests that only NK2 receptors in the muscularis mucosae and NK1
      receptors in the mucosa are physiologically relevant. In conclusion, substance P
      induced responses in the rat colon are region-specific and not mediated by a
      single NK receptor subtype common to both structures.

PMID- 16614961
TI  - Relationships between intragastric food maldistribution, disturbances of antral
      contractility, and symptoms in functional dyspepsia.
AB  - We investigated the relationships between intragastric food maldistribution and
      antral dysmotility in functional dyspepsia, and whether these abnormalities
      relate to meal-induced symptoms. Intragastric distribution of food throughout
      gastric emptying was determined in patients (n = 24) and controls (n = 38) after
      a liquid nutrient meal labeled with (99m)technetium phytate. Antral contractility
      was also periodically assessed by dynamic scintigraphy and postprandial symptoms
      were monitored with visual analog scales. Residence of food in the proximal
      stomach was decreased in 8 (33%) and antral contractility was increased in 9
      (37.5%) and decreased in 2 (8%) patients. Proximal and distal stomach motor
      abnormalities were neither significantly correlated nor associated. Increased
      antral contractility was significantly correlated (Rs = 0.54; P < .01) with
      postprandial nausea. We conclude that diminished residence of food in the
      proximal stomach and disturbed antral contractility occur independently in
      different subsets of functional dyspepsia patients. Increased antral
      contractility seems to play a role in postprandial nausea in functional
      dyspepsia.

PMID- 16614962
TI  - A novel external esophageal perfusion model for reflux esophageal injury.
AB  - The current animal models of esophagitis and Barrett's esophagus consist of
      surgeries that divert the gastroduodenal contents to the esophagus. The
      limitations of these models are the inability to control the amount and
      concentration of the refluxate and the causing of significant postoperative
      stress and morbidity. Eighteen adult rats were cannulated at the upper esophagus
      and connected to a subcutaneous osmotic micropump to perfuse the esophageal lumen
      with bile and acid. Animals were sacrificed after 7 days of perfusion.
      Histological changes were determined. Cell proliferation, apoptosis, lipid
      peroxidation, and glutathione were measured. Histopathological changes in the
      bile- or acid-perfused esophagus were consistent with the findings associated
      with reflux esophagitis. Enhanced proliferation and apoptosis were seen, along
      with increased oxidative stress. The external esophageal perfusion model enabled
      precise control of the injurious agent. It induced the histologic and cellular
      injury of reflux esophagitis after 7 days.

PMID- 16614963
TI  - Three cases of adenocarcinoma arising in extremely long-segment Barrett's
      esophagus.

PMID- 16614964
TI  - Factors associated with the development of reflux esophagitis after Helicobacter
      pylori eradication.
AB  - We investigated whether Helicobacter pylori (HP) eradication increases the
      incidence of reflux esophagitis (RE) in patients with peptic ulcers. From 2001
      2005 consecutive out patients with peptic ulcers and HP received eradication and
      were followed endoscopically. HP was cured in 119 and RE developed in 33 of the
      153 patients. RE developed in 24 of the 119 HP-eradicated patients and 9 of the
      34 HP-persistent patients. The estimated RE occurrence rate within 1 year was
      higher in the HP-eradicated patients than in the HP-persistent patients, but it
      was reversed at 2 years by the Kaplan-Meier analysis. In 76 patients follow up
      for > or = 18 months, hiatal hernia, duodenal ulcer, and eradication failure were
      significantly associated with the increased RE rate by univariate and
      multivariate analysis. The follow-up period after HP eradication affected the RE
      occurrence rate, and eradication failure significantly increased the RE
      development in patients followed up for > or = 18 months.

PMID- 16614965
TI  - Clinical significance and outcome of gastric mucosal erosions: a long-term follow
      up study.
AB  - Our purpose was to evaluate the long-term clinical significance of gastric
      erosions. A series of 117 patients with gastric erosions without peptic ulcer
      disease, and matched controls were studied in 1974-1979. All available subjects
      were reinvestigated 17 years later, including detailed clinical history and
      laboratory analysis. At follow-up, erosions were still more prevalent (39%;
      20/50) in the erosion group than in the controls (11; 7/66). In Helicobacter
      pylori-positive participants, peptic ulcer or a scar was more common in the
      erosion group (17%; 9/52) than in controls (5%; 3/66). Overall malignancy rate
      was higher in controls (15%; 17/117) than in erosion group (5%; 6/117; P = .025),
      but no other differences were seen between the groups or related with current
      erosion. We conclude that a significant proportion of gastric erosions are
      chronic or recurrent but mostly without serious complications. However, H. pylori
      positive patients with erosions have significant risk to develop a peptic ulcer.

PMID- 16614966
TI  - Rat gastric gelatinase induction during endotoxemia.
AB  - Despite continued investigation, the pathogenesis of tissue injury secondary to
      sepsis remains elusive. Further evaluation of the mechanisms by which endotoxemia
      and sepsis induce tissue injury is necessary to formulate rational and effective
      treatment strategies. The purpose of these studies was to evaluate the role of
      the matrix metalloproteinases MMP-2 and MMP-9 in gastric injury during
      lipopolysaccharide induced endotoxemia. Lipopolysaccharide increased gastric
      gelatinase activity as determined by in situ and gelatin zymography.
      Specifically, lipopolysaccharide induced MMP-2, MMP-9, and tissue inhibitor of
      metalloproteinase-1 (TIMP-1) transcription, with subsequent increases in MMP-2
      and TIMP-1 protein expression. Furthermore, selective metalloproteinase
      inhibition ameliorated gastric injury in this model. These data suggest that
      lipopolysaccharide-induced gastric injury is mediated, at least in part, by
      increased MMP-2 production.

PMID- 16614967
TI  - The effect of opioids on the development of postoperative intra-abdominal
      adhesions.
AB  - People addicted to opium rarely develop intra-abdominal adhesions after abdominal
      surgery. We aimed to evaluate the effect of opium or morphine on preventing
      postoperative adhesions in rats. Sixty-three rats were randomly divided into a
      control group, opium-addicted group, and morphine-addicted group in a double
      blind study. Drug dependency was checked by using naloxone. Animals were then
      operated on and the cecum was abraded. At reoperation 3 weeks later the magnitude
      of adhesions was evaluated by a scoring system. There was a significant
      difference between the control, opium-addicted, and morphine-addicted groups with
      regard to the length (P < .001), thickness (P < .05), and severity of adhesions
      (P < .05). Opium or morphine reduces the severity of postoperative adhesions.
      Elucidation of the opioid receptor(s) involved in this process would enable the
      use of selective ligands and offer a pharmacologic strategy in preventing
      adhesion formation.

PMID- 16614968
TI  - Experimental study evaluating the effect of a barrier method on postoperative
      intraabdominal adhesions.
AB  - The purpose of this animal study was to determine if tissue glue-coated collagen
      sponge is an effective barrier method to prevent localized adhesions in a
      modified rabbit sidewall model. Rabbits were divided into two groups and
      underwent laparotomy with subsequent creation of a cecal wound according to the
      rabbit sidewall model. Rabbits of group I (treatment group; n = 10) were treated
      with a TachoComb H patch placed on the defect, whereas group II animals (control
      group; n = 6) did not receive further treatment. All animals were sacrificed 2
      weeks postoperatively and adhesions were evaluated using special adhesion score.
      A further six rabbits underwent TachoComb H application at the cecum to
      investigate the histological changes during a course of 12 weeks. The average
      adhesion scores were significantly (P < 0.05) reduced in the treatment group
      compared to the controls. Histologically the TachoComb H patch was surrounded by
      granulation tissue without signs of infection. Tissue glue-coated collagen sponge
      (TachoComb H) is effective to prevent localized intraabdominal adhesions in the
      modified rabbit sidewall model.

PMID- 16614969
TI  - Inhibition of inducible nitric oxide synthase prevents hepatic, but not
      pulmonary, injury following ischemia-reperfusion of rat liver.
AB  - The aim of this study was to investigate the contribution of inducible nitric
      oxide synthase (iNOS)-derived nitric oxide on the liver and lung injury following
      hepatic ischemia-reperfusion (I/R) using a novel and potent iNOS inhibitor, ONO
      1714. Rats were subjected to 90 min of partial hepatic ischemia followed by 3, 6,
      12, and 24 hr of reperfusion. Expression of iNOS mRNA peaked at 3 hr of
      reperfusion in the liver and lung. Plasma nitric oxide levels were increased
      fourfold at 24 hr of reperfusion and plasma ALT was increased, reaching a peak at
      12 hr of reperfusion; both were significantly inhibited by ONO-1714. Histological
      examination revealed extensive liver damage, whereas this was not seen in the ONO
      1714 group. Lung injury was not significantly changed in groups with versus
      without ONO-1714. Nitrotyrosine expression was seen in regions similar to those
      of the histological injuries of the liver, while this staining was absent in the
      ONO-1714 group. These data show that generation of peroxynitrite could be
      involved in the pathogenesis of liver injury but not lung injury after hepatic
      I/R. Inhibition of iNOS could be applied for attenuation of liver injury
      following hepatic I/R.

PMID- 16614970
TI  - Estrogen-induced proliferation in cultured hepatocytes involves cyclin D1,
      p21(Cip1) and p27(Kip1).
AB  - The purpose of this study was to establish if estrogen-induced hepatocyte
      proliferation in vitro involves the cell cycle regulators cyclin D1, p21(Cip1),
      and p27(Kip1). Male rat hepatocytes were cultured in presence of 17-beta
      estradiol (E2) +/- ICI-182780, a pure estrogen antagonist, and [3H]-thymidine, as
      required. DNA synthesis as well as p21(Cip1), p27(Kip1), and cyclin D1mRNA and
      protein levels were evaluated at different times (12, 24, 36, and 48 hours) of
      incubation. E2-increased DNA synthesis was correlated with cyclin D1 and
      p21(Cip1) (mRNA and protein) variations that were reversed by the addition of ICI
      182780. p27(Kip1) protein levels progressively increased regardless of the
      presence of E2 or ICI-182780. Our data confirm that estrogens' stimulatory effect
      is related to their ability to increase cyclin D1 levels. The increase of
      p21(Cip1) is probably related to the reentry of hepatocytes in the quiescent
      state. p27(Kip1) protein is not able to arrest hepatocyte proliferation.

PMID- 16614971
TI  - Zonation of hepatic bile salt transporters.
AB  - Pericentral and periportal hepatocytes differ in their capacity to eliminate and
      velocity of eliminating bile acids and other organic anions. We wonder whether
      differences in the distribution of anion transporters (ntcp [M77479], besp
      [NM_031760], mrp2 [NM_012833], oatp1 [NM_017111], oatp2 [NM_131906]) cause the
      differences in bile acid excretion. Therefore, we analyzed the distribution of
      these anion transporters in periportal and pericentral cells by immunohistology,
      their mRNA by quantitative PCR, and regulating nuclear factors (NF-kappaB, HNF1,
      HNF3, HNF4, FXR, PXR) by gel shift assay. We did not find any differences in
      nuclear factors or regarding the proteins that could explain the zonal
      differences in anion transport.

PMID- 16614972
TI  - Differentiating acute hepatitis B from the first episode of symptomatic
      exacerbation of chronic hepatitis B.
AB  - In countries with intermediate or high endemicity for chronic hepatitis B virus
      (HBV) infection, exacerbations of chronic hepatitis B (CHB) are common. We
      studied the clinical, biochemical, and virologic characteristics of patients
      first presenting clinically with features of acute icteric hepatitis B, to
      identify features that might differentiate between acute viral hepatitis B (AVHB)
      from first episode of exacerbation of chronic hepatitis (ECHB). We
      retrospectively analyzed 79 patients (mean age 35.4 +/- 14 years; M:F = 60:19)
      who first presented clinically as AVHB, within 4 weeks of onset of symptoms.
      Patients who on follow-up cleared HBsAg and/or did not develop any clinical,
      radiologic, or histologic evidence of chronic liver disease (CLD) were
      categorized as AVHB (group 1). Patients who had persistence of HBsAg and
      developed clinical, biochemical, radiologic, or histologic evidence of chronic
      liver disease were categorized as ECHB (group 2). Forty-nine patients were in
      group 1 and 30 in group 2. The 2 groups were comparable with respect to prodrome,
      onset of jaundice, serum bilirubin, ALT, prothrombin time prolongation, serum
      albumin, and A/G ratio. Among group 1 patients, 78% had IgM anti-HBc positive in
      titers > 1:1000; in group 2, there were negative or positive in titers < 1:1000
      in 70% patients (P < .001). Forty-seven of 49 (95.9%) patients in group 1 had HBV
      DNA levels < 0.5 pg/mL, whereas 26 of 30 (86.73%) patients in group 2 had levels
      > 0.5 pg/mL (P < or = .001). Quantitative HBV DNA and IgM anti-HBc titers at
      initial presentation can differentiate patients with a true episode of acute
      hepatitis B from patients with first episode of symptomatic exacerbation of
      chronic hepatitis B. Clinical and biochemical features do not help in
      differentiating the two.

PMID- 16614973
TI  - De novo hepatocellular carcinoma in a patient with chronic hepatitis C 5 years
      after sustained virologic response to interferon/ribavirin therapy.

PMID- 16614974
TI  - A long-term glycyrrhizin injection therapy reduces hepatocellular carcinogenesis
      rate in patients with interferon-resistant active chronic hepatitis C: a cohort
      study of 1249 patients.
AB  - To elucidate the influence of a glycyrrhizin therapy on hepatocarcinogenesis rate
      in interferon (IFN)-resistant hepatitis C, we retrospectively analyzed 1249
      patients with chronic hepatitis with or without cirrhosis. Among 346 patients
      with high alanine transaminase value (twice or more of upper limit of normal),
      244 patients received intravenous glycyrrhizin injection and 102 patients did
      not, after judgment of IFN resistance. Crude carcinogenesis rates in the treated
      and untreated group were 13.3%, 26.0% at the 5th year, and 21.5% and 35.5% at the
      10th year, respectively (P = .0210). Proportional hazard analysis using time
      dependent covariates disclosed that glycyrrhizin treatment significantly
      decreased the hepatocarcinogenesis rate (hazard ratio 0.49, 95% confidence
      interval 0.27-0.86, P = .014) after adjusting the background features with
      significant covariates. Glycyrrhizin injection therapy significantly decreased
      the incidence of hepatocellular carcinoma in patients with IFN-resistant active
      chronic hepatitis C, whose average aminotransferase value was twice or more of
      upper limit of normal after interferon.

PMID- 16614975
TI  - Primary hepatocellular carcinoma detected long after tumor markers and lymph node
      metastases--beyond our vision?

PMID- 16614976
TI  - Mutations of beta-catenin and KRAS in colorectal carcinomas.

PMID- 16614977
TI  - Effect of colitis and ileoanal pouch on biliary enrichment of ursodeoxycholic
      acid in primary sclerosing cholangitis.
AB  - In primary sclerosing cholangitis (PSC), biliary enrichment of ursodeoxycholic
      acid (UDCA) may represent the decisive factor for its presumable beneficial
      effect. Up to now it is not clear how colitis and colectomy with ileo-anal pouch
      affect the biliary enrichment of UDCA and the biliary bile acid composition. We
      determined the biliary bile acid composition in 63 patients with PSC including 7
      patients with ileo-anal pouch, 31 patients with colitis, and 25 patients without
      colitis. No differences existed between patients with and those without colitis.
      In patients with colectomy and pouch at a UDCA dose of 17.7 +/- 1.6 mg/kg (n =
      7), biliary UDCA represented 46.4 +/- 6.7% (mean +/- SD) of total bile acids. An
      increase in the dose in six pouch patients from 12.5 +/- 0.9 to 22.3 +/- 1.6
      mg/kg led to a slight increase in biliary enrichment of UDCA, from 39.8 +/- 8.1
      to 49.4 +/- 10.7%. In five of seven patients with ileo-anal pouch, biliary UDCA
      enrichment was within the normal range, and in two of seven it was permanently or
      intermittently abnormally low. During UDCA treatment, in pouch patients the
      biliary content of deoxycholic acid and lithocholic acid was reduced, whereas all
      other bile acids were unchanged. In a minority of patients with ileo-anal pouch,
      biliary enrichment of UDCA may be markedly reduced, whereas patients with colitis
      have a biliary UDCA enrichment not different from that of patient without
      colitis.

PMID- 16614978
TI  - Biliary cystadenomas: hormone receptor expression and clinical management.
AB  - Biliary cystadenomas with mesenchymal stroma are neoplasms whose growth may be
      hormone sensitive. This study profiled the immunohistochemistry of these lesions
      to clarify the pathophysiology and define clinical management. Twelve patients
      with biliary cystadenomas were identified. Tissue was tested with a panel of
      probes including estrogen and progesterone receptors and compared to pancreatic
      and ovarian cystadenomas. Epithelial ER, PR, CD117, or SMA expression was
      negative in all three tumors. Epithelial CD10 expression was seen in 60% biliary,
      75% pancreatic, and 0% ovarian tumors. Biliary cystadenoma stromal expression was
      ER+ (70%), PR+ (60%), CD10+ (40%), and c-kit+ (0%). Symptoms were seen in 92%
      patients. Percutaneous sclerotherapy and incomplete resection were associated
      with recurrence. Enucleation was the least morbid surgical technique. A role for
      hormonally mediated growth of biliary cystadenomas occurring through the stroma,
      rather than the epithelium, is suggested. Management remains complete surgical
      resection.

PMID- 16614979
TI  - Mucinous cystic neoplasm of the pancreas with ovarian-type stroma arising in the
      head of the pancreas: case report and review of the literature.

PMID- 16614981
TI  - Sandifer syndrome posturing: relation to abdominal wall contractions,
      gastroesophageal reflux, and fundoplication.
AB  - Sandifer syndrome designates abnormal posturing in patients with gastroesophageal
      reflux. To explore its mechanisms via examining relationships among Sandifer
      syndrome posturing, abdominal wall contractions, and reflux episodes, we studied
      an affected child in detail. The study utilized esophageal pHmetry, surface
      electromyography, and split-screen videography. The multichannel physiologic
      study demonstrated association of rectus abdominis contraction with onset of
      reflux episodes (P < 0.001) and association of reflux episodes with Sandifer
      syndrome posturing. This child's subsequent course confirmed his diagnosis and
      suggested mechanisms of the association of reflux and Sandifer syndrome. We
      conclude that abdominal wall contractions may induce reflux episodes. Sandifer
      syndrome may be due to gastroesophageal reflux even without hiatal hernia,
      macroscopic esophagitis, or reflux symptoms. Despite the absence of more typical
      reflux symptoms and failure to respond to very aggressive medical therapy,
      Sandifer syndrome may resolve after fundoplication.

PMID- 16614982
TI  - Non-Helicobacter bacterial flora rarely develops in the gastric mucosal layer of
      children.
AB  - Non-Helicobacter bacteria can be cultured from the gastric mucosa in adults but
      in children, there are no studies about such microflora. The purpose of this
      study, therefore, was to clarify whether gastric biota develops in children. In
      10 children and 10 adults or elderly (5 H. pylori-infected and 5 uninfected in
      each group), biopsy specimens of the gastric antrum and corpus and gastric juice
      were studied for bacterial examinations and the data were compared between both
      age groups in relation to H. pylori status and luminal pH. Bacterial genera and
      species were analyzed using both culture and real-time polymerase chain reaction
      (PCR) with the 52 genus- and species-specific primer sets. Non-Helicobacter
      bacteria in the mucosa were cultured from all adult patients, whereas
      microorganisms were cultured in only one child (p < .001). Gastric pH was lower
      in children (median, 1.4) than in adults (median, 2.6) (p < .005). The grade of
      endoscopic gastric atrophy was moderate or severe in 8 adults, but absent or mild
      in all 10 children. Among adults, there was a significant positive correlation
      between gastric pH and total bacterial counts of both the mucosa and juice. These
      data indicate that impaired gastric acid secretion associated with long-term H.
      pylori infection enables non-Helicobacter bacteria to colonize in the human
      stomach. Such microorganisms rarely colonize in the gastric mucosa in children
      regardless of H. pylori status.

PMID- 16614983
TI  - Acute on chronic intestinal pseudo-obstruction as a cause of death in a
      previously healthy twenty-year-old male.

PMID- 16614984
TI  - Effects of intraduodenal glucose concentration on blood pressure and heart rate
      in healthy older subjects.
AB  - The aims of this study were to determine whether the hypotensive and heart rate
      responses to small intestinal glucose infusion are dependent on the glucose
      concentration. Eight healthy subjects, aged 65-78 years, were studied on 3
      separate days in random order. Each subject received intraduodenal infusions of
      50 g of glucose in either 300 mL (16.7%), 600 mL (8.3%), or 1200 mL (4.1%) of
      saline (0.9%) at a rate of 3 kcal/min for 60 minutes (t = 0-60 minutes), followed
      by saline (0.9%) for a further 60 minutes (t = 60-120 minutes). During the
      infusions, blood pressure (systolic and diastolic) and heart rate were measured
      every 3 minutes, and blood glucose concentrations every 15 minutes. Systolic and
      diastolic blood pressure fell (P < .0001), and heart rate and blood glucose
      increased (P = .0001 for both) over time, during all 3 infusions. Between t = -2
      120 minutes, there was no difference in systolic blood pressure (P = .20),
      diastolic blood pressure (P = .61), or heart rate (P = .09) over the study days.
      There was also no significant difference in the glycemic response to the
      infusions. We conclude that in healthy older subjects, glucose concentration does
      not affect the blood pressure or heart rate responses to intraduodenal glucose
      and that, therefore, the magnitude of the postprandial fall in blood pressure
      induced by oral glucose is likely to depend primarily on the small intestinal
      glucose load.

PMID- 16614985
TI  - Increased antioxidant capacity of serum did not prevent lipid peroxidation in the
      intermittent ischemia-reperfusion of rat small intestine.
AB  - Changes in small molecular antioxidants were followed up in a model of small
      intestinal ischemia in Wistar rats to evaluate their possible role in ischemic
      preconditioning. The superior mesenteric artery was occluded either for 60
      minutes only or for 60 minutes preceded by one to three 15-minute periods of
      ischemia with 5-minute reperfusion periods interposed. Total antioxidant capacity
      (TRAP) in serum, serum antioxidants (uric acid, ascorbic acid, bilirubin), and
      the thiobarbituric acid reactive substances in both serum and mucosa were
      measured. An increase in TRAP observed after 60 minutes of ischemia was prevented
      in preconditioned animals. Ascorbic and uric acid concentrations increased
      generally in comparison to intact controls, but this increase was not sufficient
      to prevent lipid peroxidation in serum and intestinal mucosa. In short, the small
      molecular antioxidants measured did not contribute to the phenomenon of ischemic
      preconditioning.

PMID- 16614986
TI  - Selective COX-2 inhibition reduces leukocyte sticking and improves the
      microcirculation in TNBS colitis.
AB  - The role of cyclooxygenase-2 inhibitors in the course of experimental colitis is
      controversially discussed. The aim of this study was to evaluate leukocyte
      endothelium interaction and colitis activity after applying the selective
      cyclooxygenase-2 inhibitor NS-398 in a rat trinitrobenzene sulfonic acid (TNBS)
      colitis model. The acute phase of TNBS colitis is characterized by a significant
      reduction of capillary blood flow, capillary density, diuresis, and weight and a
      significant increase in capillary permeability, leukocyte sticking, and
      hematocrit. Applying the selective cyclooxygenase-2 inhibitor NS-398 leads to a
      significant improvement of all microcirculatory parameters and clinical findings
      compared to the (untreated) colitis group. There are no histopathological
      differences between the individual colitis groups. Acute colitis is characterized
      by an extensive disturbance of microcirculation together with signs of systemic
      inflammatory response syndrome. These alterations are significantly improved by
      inhibiting cyclooxygenase-2. The results support the described correlation
      between cyclooxygenase activation and leukocyte-endothelium interaction.
      Moreover, they underscore the postulated relation between leukocyte-endothelium
      interaction and capillary blood flow.

PMID- 16614987
TI  - Inhibitory effects of sildenafil on small intestinal motility and myoelectrical
      activity in dogs.
AB  - Previous studies have shown that sildenafil inhibits the esophageal motility in
      both humans and animals. The aim of this study was to investigate the effects of
      sildenafil on intestinal myoelectrical activity and motility. The study was
      composed of 2 experiments and performed in 7 healthy female dogs with a duodenal
      cannula 20 cm beyond pylorus (19-26 kg). The first experiment was designed to
      study the effects of sildenafil on intestinal myoelectrical activity and it
      included 2 sessions each consisting of 30-minute baseline, 15-minute
      posttreatment (placebo or 100 mg sildenafil) and 90 minutes after a liquid meal.
      Intestinal myoelectrical activity was recorded during the entire experiment
      period. The second experiment was aimed to investigate the effect of sildenafil
      on intestinal motility and was performed immediately after a solid meal.
      Intestinal motility was measured by a manometric catheter inserted into the small
      intestine via the duodenum cannula for 30 minutes at baseline and 60 minutes
      after sildenafil. Sildenafil significantly reduced the amplitude but had no
      effect on the frequency and regularity of the intestinal myoelectrical activity.
      Sildenafil significantly inhibited postprandial intestinal contractions. Although
      the frequency of the contractions was not altered, the mean area under the curve
      was significantly reduced during the first 30 minutes (P < .03) and second 30
      minutes after sildenafil (P < .03); the power of intestinal contractile
      activities was also significantly reduced during the first 30 minutes (P < .0004)
      and second 30 minutes after sildenafil (P < .0003) in comparison with baseline.
      In conclusion, sildenafil inhibits the amplitude of both intestinal contractile
      activity and intestinal slow waves.

PMID- 16614988
TI  - An inverse correlation of human peripheral blood regulatory T cell frequency with
      the disease activity of ulcerative colitis.
AB  - Evidence suggests that CD4+CD25+ regulatory T cells play a crucial role in the
      suppression of intestinal inflammation. However, their role in the suppression of
      inflammatory bowel disease has not yet been addressed. We examined the proportion
      of regulatory T cells in inflammatory bowel disease. First, we isolated
      CD4+CD45RO+CD25+ T cells from the peripheral blood of healthy persons and showed
      that these cells suppressed T cell proliferation profoundly and expressed FoxP3
      abundantly, revealing that they are regulatory cells. Then the proportion of
      CD45RO+CD25+ in peripheral blood CD4+ T cells was analyzed in patients and
      healthy controls by flow cytometry. CD4+CD45RO+CD25+ T cell frequency was
      significantly lower in active ulcerative colitis than in the control and inactive
      ulcerative colitis. CD4+CD45RO+CD25+ T cell frequency was inversely correlated
      with the clinical and endoscopic severity of ulcerative colitis. These results
      suggest that a deficiency of regulatory T cells is associated with the
      progression of ulcerative colitis.

PMID- 16614989
TI  - Increased frequency of mutations in the gene responsible for familial
      Mediterranean fever (MEFV) in a cohort of patients with ulcerative colitis:
      evidence for a potential disease-modifying effect?
AB  - The MEFV gene, responsible for familial Mediterranean fever (FMF), is involved in
      inflammatory reactions through altered leukocyte apoptosis, secretion of
      interleukin (IL)-1beta, and activation of the NF-kappa B pathway. Ulcerative
      Colitis (UC) and FMF are both characterized by a recurrent pattern of
      presentation with periods of remission and flares associated with neutrophilic
      infiltration at the site of injury. The aim of this study was to investigate the
      possible correlation between UC and MEFV gene alterations. Twenty-five
      consecutive, first-diagnosed and untreated UC patients, 28 control patients with
      rheumatoid arthritis, and 65 normal individuals were analyzed. Nonisotopic RNase
      Cleavage Assay (NIRCA) was applied as a first-step mutational screening method of
      exons 10 and 2 of MEFV gene; direct sequencing was subsequently performed to
      confirm the results. MEFV mutations were identified in 7 (3 M694V/0, 2 M680I/0, 1
      E148Q/E148Q, and 1 A744S/0) out of 25 UC patients versus 1 (M694V/0) out of 28
      rheumatoid arthritis patients (P = .0199) and 1 (M694V/0) out of 65 healthy
      controls (P = .0004). Four out of 7 patients with MEFV mutations had inflammatory
      arthritis, a clinical finding that was not observed in the 18 UC patients with
      unmutated MEFV (P = .0028). Patients with UC almost universally carried the T A C
      G MEFV exon 2 haplotype in contrast with normal individuals (P < .0001) and FMF
      patients (P = .0310). In conclusion the increased frequency of mutations of MEFV
      in UC patients, especially in those with episodic arthritis, suggests a possible
      modifying effect of MEFV in the disease process and its localization within the
      joint. The difference in distribution of MEFV exon 2 haplotypes between UC
      patients and both FMF patients and normal individuals, suggests that UC patients
      constitute a genetically distinct population. Larger, longitudinal studies are
      needed to confirm these initial findings.

PMID- 16614990
TI  - Attenuation of colonic inflammation by PPARgamma in intestinal epithelial cells:
      effect on Toll-like receptor pathway.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear
      receptor highly expressed in the colon and playing an anti-inflammatory role
      through inhibition of the NF-kappaB pathway. Toll-like receptor 4 (TLR4) has been
      known to mediate LPS-induced cellular signaling through activation of NF-kappaB
      pathway in intestinal epithelial cells. The aims of this study were to evaluate
      attenuation of inflammation by PPARgamma in intestinal epithelial cells and to
      study the possible relation between PPARgamma and TLR4. HT-29 human epithelial
      cells were stimulated with LPS (20 microg/ml) and PPARgamma ligand, 15d-PGJ2 (10
      microM), or with LPS (20 microg/ml) alone for 24 hr. COX-2, IL-8, TLR4, and
      PPARgamma mRNA expression was assessed by RT-PCR. IL-8 protein levels and TLR4
      protein expression were analyzed by ELISA and Western blot, respectively. To
      evaluate the action mechanisms of PPARgamma ligand, Western blot analysis for
      IkappaBalpha degradation was performed. Costimulation with LPS and PPARgamma
      ligand in comparison to LPS stimulation alone (1) decreased COX-2, IL-8 mRNA
      expression and IL-8 protein secretion, (2) decreased TLR4 mRNA and protein
      expression, and (3) decreased PPARgamma mRNA expression. PPARgamma ligand delayed
      LPS-induced IkappaBalpha degradation. These findings suggest that PPAR-gamma
      ligands suppress inflammation in intestinal epithelial cells. PPARgamma and TLR,
      these two antagonistic signaling pathways in intestinal epithelial cells may be
      partially cross-linked.

PMID- 16614991
TI  - Antioxidant therapy with N-acetylcysteine plus mesalamine accelerates mucosal
      healing in a rodent model of colitis.
AB  - The aims of this study were to examine the ability of the antioxidant N
      acetylcysteine (NAC) and mesalamine (5-ASA) alone and in combination to affect
      TNBS-induced colitis in rat. Three days following induction of TNBS colitis rats
      were randomized to receive daily intracolonic treatment with NAC, 5-ASA, and NAC
      plus 5-ASA for 5 or 8 days. At the end of the treatment period macroscopic and
      microscopic colonic injuries were scored. Myeloperoxidase (MPO) activity and
      cytokine gene expression were measured in colonic tissues. Results indicated that
      treatment with NAC plus 5-ASA caused a significantly greater reduction in colonic
      injury than either agent alone. Furthermore, combination therapy inhibited
      significantly MPO activity and inflammatory cytokine gene expression in the
      distal colon of TNBS-treated animals. The beneficial effects of NAC plus 5-ASA on
      reduction of colonic injury and promotion of healing were most evident after 8
      days of treatment.

PMID- 16614992
TI  - Distribution of common CARD15 variants in patients with sporadic Crohn's disease:
      cases from Turkey.
AB  - Three common genetic variations, namely, R702W, G908R, and 1007fs, on CARD15 have
      been shown to increase the risk for Crohn's disease (CD) in Caucasian
      populations. In this study the frequencies of these CARD15 variants were
      determined by genotyping in 56 patients with CD and 100 healthy ethnically
      matched controls from Turkey. Overall frequency of all three variants was 10.7%
      in CD patients, compared with 1.5% in controls (odds ratio [OR]: 7.9). Among
      them, the frequency of the G908R variant allele was 8% in CD cases, compared with
      0% in controls (OR: 36.8). The allele frequencies of three CD-related CARD15
      variants were considerably lower in the control group compared to the reported
      Caucasian populations. Among the described CARD15 variants, G908R confers an
      increased susceptibility to CD, whereas the more frequently reported associations
      in Europeans with R702W and 1007fs are not confirmed in this Turkish population.

PMID- 16614993
TI  - Crohn's-like colitis in a patient with immunodeficiency associated with a defect
      in expression of inducible costimulator.

PMID- 16614994
TI  - Postnatal epithelial growth of the small intestine in the rat occurs by both
      crypt fission and crypt hyperplasia.
AB  - Studies of growth of the small intestine have largely concentrated on crypt
      hyperplasia rather than crypt fission. The aim of this study was to investigate
      quantitatively both crypt fission and crypt hyperplasia. DAxPVG/c rats were
      killed at 7, 11, 14, 17, 19, 21, 25, 55, and 72-73 days of life. Samples of
      jejunum at one third of the intestinal length were taken for morphometry (villous
      area, crypt area, percentage of bifid crypts, and crypt mitotic count) by
      microdissection. Growth factors and their receptors were assessed by
      oligonucleotide microarray. Crypt fission was 10.5%, 5.2%, and 1.5% at days 11,
      25, and 72-73 of life, respectively. Crypt hyperplasia increased from day 21. No
      conventional growth factor was identified during crypt fission. We conclude that
      crypt fission contributes to growth of the small intestine prior to weaning and
      crypt hyperplasia to growth after weaning.

PMID- 16614995
TI  - Preventive effects of the probiotic Escherichia coli strain Nissle 1917 on acute
      secretory diarrhea in a pig model of intestinal infection.
AB  - Pretreatment with the probiotic Escherichia colistrain Nissle 1917 (EcN) was
      assessed in a pig model of intestinal infection to prevent acute secretory
      diarrhea. In the model 10(10) colony forming units of the porcine enterotoxigenic
      Escherichia coli Abbotstown (EcA) was given via orogastric tube to weaned piglets
      at day 21 postpartum (-EcN/+EcA group, n = 7). Forty-eight hours after challenge
      electrophysiological parameters of isolated intact jejunal epithelia were
      characterized in Ussing chambers. In agreement with clinical signs of diarrhea,
      tissues of challenged animals showed an overshoot of secretory response after
      stimulation of the cAMP-mediated second messenger pathway by forskolin,
      indicating higher excitability of chloride secretory systems under infected
      conditions. The data were compared with respective measurements from animals that
      got a daily dose of 10(10) cfu of the probiotic EcN over 10 days before EcA
      challenge (+EcN/+EcA group; n = 4), from a group that received only EcN (+EcN/
      EcA; n = 4), or from a group that remained totally untreated (-EcN/-EcA; n = 6).
      EcN pretreatment completely abolished clinical signs of secretory diarrhea in
      +EcN/+EcA animals. Furthermore, jejunum epithelia of these animals did not
      exhibit an overshoot of secretory response upon stimulation with forskolin. Our
      studies demonstrate for the first time the efficacy of prophylactic EcN in pig
      small intestine for preventing an effect of toxigenic EcA. This infection model
      with freshly weaned piglets may be predestinated to further characterize EcN
      effects on the cellular level, i.e., involved second messenger pathways, or it
      may also be useful to examine the efficacy of other substrates or microbe strains
      against secretory stimuli.

PMID- 16614996
TI  - The association of Streptococcus bovis bacteremia and gastrointestinal diseases:
      a retrospective analysis.
AB  - There is a well-established association between Streptococcus bovis bacteremia
      (SBB) and colorectal cancer. However, SBB is also frequently associated with
      chronic liver disease and has been described with other gastrointestinal
      disorders. The aim of the study was to evaluate the prevalence of
      gastrointestinal disease in patients with SBB. Retrospective analysis of the
      microbiology database at Jackson Memorial Medical Center, Miami, Florida, between
      1992 and 2002, was performed. Patients' clinical records were reviewed, with
      special focus on underlying gastrointestinal disease or other major
      comorbidities. Thirty-eight patients (83%) were adults and eight (17%) were
      pediatric patients. Nineteen patients presented with gastrointestinal disorders
      associated with SBB (41%). Nine adult patients (19%) had end-stage liver disease
      (five female). Six patients had alcohol-induced liver disease (one with
      concomitant chronic hepatitis C), with the remaining three cases related to
      autoimmune hepatitis, primary biliary cirrhosis, and nonalcoholic
      steatohepatitis. Colonic neoplasms (adenocarcinoma in 3 and adenomatous polyps in
      3) were found in 6 of 10 adult patients in whom colonoscopic evaluation was
      performed. Seven adult patients had acquired immunodeficiency syndrome (AIDS)
      (18%). Mortality in the patients with AIDS and SBB was high (71%). No significant
      association with gastrointestinal diseases was found in the pediatric population.
      Bacteremia due to S. bovis in adults is frequently associated with hepatic
      dysfunction (1:4), colonic neoplasms (1:6), and AIDS (1:6). This association was
      valid for our adult population only. SBB is an early clue to the likely presence
      of these serious underlying conditions and warrants rigorous investigation when
      recognized.

PMID- 16614997
TI  - Interindividual differences in microbial counts and biochemical-associated
      variables in the feces of healthy Spanish adults.
AB  - The aim of this study was to examine, over a period of 1 year, interindividual
      variations in the most prominent and representative of the cultivatable microbial
      populations in the feces of eight healthy Spanish persons. A number of
      biochemical variables (enzyme activities and ammonium and short-chain fatty acid
      [SCFA] concentrations) thought to be influenced by the GIT microbiota were also
      analyzed. Total cultivatable microbial counts ranged from 10(10) to 10(11) cfu/g
      of feces. The largest populations were obligate anaerobes belonging to the
      Clostridium clusters, followed by species of bifidobacteria and bacteroides.
      Coliforms and lactobacilli were found at a more intermediate level (10(5)-10(9)
      cfu/g). The predominant anaerobe populations remained quite constant over time,
      but all other microbial groups showed significant interindividual differences.
      Enzyme profiles were individual-dependent, but within subjects, moderate to high
      intersample variations over time were recorded for some activities. Fecal
      ammonium concentration was the most unpredictable variable; this fluctuated
      widely between individuals and samples. Acetic acid was the most abundant SCFA in
      the feces, followed by butyric and propionic acids. SCFA concentrations also
      varied according to the individual; some subjects showed specific profiles in
      terms of SCFA composition or concentration. The fecal microbial and biochemical
      parameters studied seemed to be individual-dependent. Most variables were rather
      stable over time, while others (e.g., ammonium concentration) varied widely.

PMID- 16614999
TI  - Retroperitoneal mucinous cystadenoma.

PMID- 16614998
TI  - Identification of dominant bacteria in feces and colonic mucosa from healthy
      Spanish adults by culturing and by 16S rDNA sequence analysis.
AB  - The aim of this work was to examine by culturing the changes in the total and
      indicator populations of the feces of two individuals over 1 year and to identify
      the dominant microbial components of a single sample of feces from each donor.
      Populations and dominant bacteria from a sample of colonic mucosa from a further
      individual were also assessed. The culture results were then compared to those
      obtained with the same samples by 16S rDNA cloning and sequencing. High
      interindividual variation in representative microbial populations of the
      gastrointestinal tract (GIT) was revealed by both the culture and the culture
      independent techniques. Species belonging to Clostridium clusters (XIVa, IV, and
      XVIII) predominated in both the fecal and the mucosal samples (except in the
      mucose cultured isolates), members of Clostridium coccoides cluster XIVa being
      the most numerous microorganisms. Species of gamma-proteobacteria (Escherichia
      coli and Shigella spp.), bifidobacteria, and actinobacteria appeared in lower
      numbers than those of clostridia. From the mucosal cultured sample, only
      facultative anaerobes and bifidobacteria were recovered, suggesting destruction
      of the anaerobe population during processing. In accordance with this, the
      microbial diversity revealed by 16S rDNA sequence analysis was greater than that
      revealed by culturing. Despite large interindividual differences, distinct human
      communities may have group-associated GIT microbiota characteristics, such as the
      low number of Bacteroides seen in the subjects in this study.

PMID- 16615000
TI  - Effects of lipopolysaccharide on gastric stasis: role of cyclooxygenase.
AB  - This study was done to examine the role of cyclooxygenase (COX) in
      lipopolysaccharide (LPS)-induced gastroprotection and gastric stasis. In
      conscious rats, LPS dose and time dependently increased gastric luminal fluid
      accumulation. LPS decreased blood flow (laser Doppler) and prevented gastric
      injury from acidified ethanol at time points before significant fluid
      accumulation occurred. LPS increased COX-2 but not COX-1 expression. In contrast,
      LPS decreased gastric mucosal prostaglandin synthesis. LPS-induced gastric
      luminal fluid accumulation was negated by both nonselective COX inhibition with
      salicylate and selective COX-2 inhibition with NS-398 but not by selective COX-1
      inhibition with SC-560. Neither salicylate nor NS-398 blocked LPS-induced
      gastroprotection. LPS-induced gastroprotection does not depend entirely on
      accumulation of luminal fluid and is independent of COX-1 and COX-2. However, the
      ability of LPS to cause gastric stasis and increase gastric luminal fluid
      accumulation involves COX-2.

PMID- 16615001
TI  - Indomethacin enhances bile salt detergent activity: relevance for NSAIDs-induced
      gastrointestinal mucosal injury.
AB  - Gastroduodenal toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) is
      partly independent from cyclooxygenase inhibition, possibly related to increased
      intermixed micellar-vesicular (nonphospholipid-associated) bile salt
      concentrations thought to be responsible for bile salt cytotoxicity. We evaluated
      the effects of indomethacin on bile salt cytotoxicity with complementary in vitro
      and ex vivo systems. In the erythrocyte model, indomethacin alone did not induce
      hemolysis. In contrast, indomethacin enhanced and phospholipids decreased
      hemolysis induced by hydrophobic taurodeoxycholate (TDC). Hydrophilic
      tauroursodeoxycholate (TUDC) enhanced rather than decreased TDC-induced hemolysis
      in the presence of indomethacin. Indomethacin did not affect intermixed micellar
      vesicular bile salt concentrations or compositions. Indomethacin also increased
      TDC-induced lactate dehydrogenase release in CaCo-2 cells and bile salt-induced
      rat colonic mucosal injury, and prevented potential protective effects of TUDC in
      these systems. Our data show that indomethacin enhances bile salt-induced
      cytotoxicity without affecting intermixed micellar-vesicular bile salt
      concentrations or compositions. These findings may be relevant for gastroduodenal
      injury during NSAID therapy.

PMID- 16615002
TI  - Successful treatment of Helicobacter pylori-negative gastric MALT lymphoma with
      rituximab.
AB  - Helicobacter pylori infection is strongly associated with low-grade gastric
      lymphoma, commonly known as mucosa-associated lymphoid tissue (MALT) lymphoma. H.
      pylori eradication leads to complete remission in 80% of early stage MALT
      lymphomas. The treatment for early stage H. pylori-negative gastric MALT lymphoma
      is evolving. Rituximab, a chimeric anti-CD20 antibody, has shown response rates
      of approximately 50% with minimal toxicity in patients with B-cell non-Hodgkin
      lymphoma. We describe herein the clinical, endoscopic, and histologic features of
      a patient with H. pylori-negative gastric MALT lymphoma treated successfully with
      rituximab.

PMID- 16615003
TI  - Effects of cyclooxygenase-2 inhibition on serum and tumor gastrins and expression
      of apoptosis-related proteins in colorectal cancer.
AB  - The objective of the present study was to determine the influence of
      cyclooxygenase-2 (COX-2) inhibition by Celecoxib (CLX) in humans with distal
      colorectal adenocarcinoma (CRC) on serum and tumor levels of progastrin and
      gastrin and serum levels of proinflammatory cytokines (IL-8, TNF-alpha). In
      addition, the effects of this CLX treatment on tumor and adjacent mucosa
      expression of gastrin, its receptors (CCK2), and COX-1 and COX-2, as well as
      protein expression of the active form of nuclear factor kappa B (NFkappa B) and
      the apoptotic-related proteins Bcl-2 and survivin, have been examined. Ten distal
      CRC patients were examined twice, once before and then after 14-day treatment
      with CLX (200 mg bid). Large biopsy samples were taken from the tumor and intact
      mucosa 10 cm above the tumor. For comparison, 20 age- and sex-matched healthy
      controls were enrolled and treated with CLX as CRC patients. Serum levels of IL-8
      and TNF-alpha were measured by enzyme-linked immunosorbent assay, and serum
      levels of amidated gastrins and progastrin, by specific radioimmunoassay. The
      gene or protein expressions of progastrin, gastrin, CCK2, COX-1, COX-2, Bcl-2,
      and survivin as well as NFkappa B were determined by RT-PCR or Western blot in
      biopsy samples of tumor and intact mucosa of CRC patients. Serum IL-8 and TNF
      alpha values were severalfold higher in CRC patients than in controls. The
      increase in serum proinflammatory cytokines was accompanied by increased
      expression of the active form of NFkappa B. Serum progastrin levels were also
      found to be significantly higher in CRC than in controls. Treatment of CRC with
      CLX resulted in a significant decrease in serum levels of progastrin and this was
      accompanied by an increment in tumor expression of COX-2 with a concomitant
      reduction in gastrin, Bcl-2, survivin, and NFkappa B expression. We conclude that
      (1) distal CRC patients show significantly higher serum progastrin levels than
      matched healthy controls, confirming that this hormone may be implicated in
      rectal carcinogenesis; (2) CRC patients exhibit significantly higher serum levels
      of IL-8 and TNF-alpha than healthy controls, probably reflecting more widespread
      inflammatory reaction in the colonic mucosa in CRC; (3) gastrin, COX-2, Bcl-2,
      survivin, and NFkappa B were overexpressed in CRC tumor compared to intact
      mucosa, but treatment with CLX significantly reduced serum levels of progastrin
      and IL-8 and TNF-alpha, which could mediate the up-regulation of COX-2 in CRC;
      and (4) CLX also enhanced expression of COX-2, while inhibiting the expression of
      gastrin, Bcl-2, survivin, and NFkappa B, suggesting that COX-2 inhibition might
      be useful in chemoprevention against CRC, possibly due to suppression of the
      antiapoptotic proteins and reduction in progastrin-induced and NFkappa B-promoted
      tumor growth.

PMID- 16615004
TI  - Upper gastrointestinal bleeding caused by small-cell lung cancer: a case report.

PMID- 16615005
TI  - Intussuscepted sigmoid colonic lipoma mimicking carcinoma.

PMID- 16615006
TI  - Diabetes: one of few remarkable differences in clinicopathologic features between
      cirrhotic and noncirrhotic Swedes with hepatocellular carcinoma.
AB  - The prognosis of hepatocellular carcinoma (HCC) is usually very poor, so
      increased knowledge of clinicopathologic characteristics and etiologic factors
      may improve the clinical handling. Because HCC in many patients is unrecognized
      before death, it is of particular interest to study cases from a period with a
      high autopsy frequency. The records and liver biopsies from all patients with a
      diagnosis of primary liver cancer in Goteborg, Sweden, during a 22-year period
      were scrutinized. Only patients with evaluable non-neoplastic liver tissue were
      included in the final analysis. The majority (95%) of 478 HCC cases were
      autopsied and cirrhosis of the liver could be established in 71%. At
      presentation, general paramalignant symptoms such as malaise, weight loss,
      anorexia, and hepatomegaly (84%) were common irrespective of cirrhosis.
      Alcoholism and diabetes mellitus were each significantly more common among
      cirrhotics (29% and 20%, respectively; P < .001), than among noncirrhotics, in
      which cholelithiasis was more common (54%; P < .001). The correlation between
      diabetes and cirrhosis was independent of reported alcoholism. In an unselected
      population in a low HCC incidence area, there are few differences in
      clinicopathologic features between cirrhotic and noncirrhotic patients. Diabetes
      mellitus seems to play an etiologic role in HCC in cirrhotics, and cholelithiasis
      in noncirrhotics.

PMID- 16615007
TI  - Individuals homozygous for the H63D mutation have significantly elevated iron
      indexes.
AB  - Our objective was to assess the iron indexes of patients with one or more
      mutations of the HFE gene with a specific interest in studying the effect of the
      H63D/H63D genotype. Eight hundred twenty subjects who underwent HFE mutational
      testing for C282Y and H63D mutations were retrospectively identified. Data
      collected included age, gender, HFE genotype, and values for serum ferritin, iron
      saturation, aspartate aminotransferase (AST), and alanine aminotransferase (ALT).
      Compared to the Wild/Wild genotype (0.34 +/- 0.17), genotypes H63D/C282Y (0.44 +/
      0.14 P < 0.01), H63D/H63D (0.51 +/- 0.21 P < 0.01), and C282Y/C282Y (0.64 +/-
      0.20 P < 0.01) had significantly higher transferrin saturation levels and were
      independent predictors of higher iron saturation in multivariate regression
      analysis. Compared to the Wild/Wild genotype, no abnormal HFE genotypes had
      significantly higher ferritin levels, although the genotype H63D/H63D was an
      independent predictor of higher serum ferritin (P = 0.02) in regression analysis.
      There was no significant difference in the proportion of patients with abnormally
      elevated AST (P = 0.64) or ALT (P = 0.80) between groups. H63D homozygotes have
      elevated transferrin saturation compared to the Wild genotype, comparable to that
      of C282Y homozygotes and compound heterozygotes. The clinical significance of
      this finding is unclear but warrants further study.

PMID- 16615008
TI  - A decrease in AFP level related to administration of interferon in patients with
      chronic hepatitis C and a high level of AFP.
AB  - It is known that there is a very high incidence of hepatocellular carcinoma (HCC)
      among patients with type C chronic hepatitis and cirrhosis, and alpha 
      fetoprotein (AFP) has been widely used as a diagnostic marker for HCC. However,
      there are some patients showing continuous high AFP values but no evidence of
      HCC, and some studies have defined such patients as a high-risk group for HCC. In
      vitro study has shown that interferon (IFN) inhibits cell proliferation and
      enhances apoptosis as well as specific cytotoxic T lymphocytes against HCC,
      resulting in direct anticancer actions. In this study, we investigated the effect
      of IFN on AFP changes in chronic hepatitis C patients. Of 40 patients with
      chronic hepatitis C in whom diagnostic imaging confirmed the absence of HCC, 24
      patients showed high pretreatment AFP values (high AFP group: AFP level > 10
      ng/dl; mean +/- SD, 46.3 +/- 41.5 ng/dl) and 16 showed low pretreatment AFP
      values (low AFP group: pretreatment AFP level < or = 10 ng/dl; mean +/- SD, 5.3
      +/- 2.2 ng/dl). Pretreatment clinical parameters were statistically evaluated in
      relation to the AFP value. In the high AFP group, the platelet count, albumin
      level, and prothrombin (%) were significantly lower (P = 0.047, P = 0.0002, and P
      = 0.044, respectively), suggesting that AFP value increases with advancing liver
      disease. Subsequently 27 patients were administered IFN (IFN group), and the
      remaining 13 patients were administered Stronger Neo-minophagen C (SNMC), a
      glycyrrhizin preparation (SNMC group), as a control group receiving liver
      protective therapy. Alanine aminotransferase was reduced in both the IFN and the
      SNMC group (mean, 132.56 to 60.07 mg/ml [P < 0001] and 147.85 to 56.23 mg/ml [P =
      0.0240], respectively). AFP was significantly reduced in the IFN group (mean,
      30.03 to 12.65 ng/ml; P = 0.0034), but there was no significant change in AFP in
      the SNMC group (mean, 29.70 to 39.17 ng/ml). AFP is useful for diagnosing HCC;
      however, some patients show a persistently high AFP level in the absence of HCC,
      and these patients have been described as a high-risk group for HCC. In this
      study, we found that IFN therapy but not SNMC universally reduced the AFP
      baseline. Since AFP is a significant predictor for HCC, therapeutic strategies
      for hepatitis C, e.g., long-term low-dose IFN treatment, may reduce
      hepatocarcinogenesis.

PMID- 16615009
TI  - Lupus-related hepatitis: complication of lupus or autoimmune association? Case
      report and review of the literature.

PMID- 16615011
TI  - [T-lymphocyte subgroups and tuberculin skin test reactivity in patients with
      chronic renal failure].
AB  - As anergy is common in patients with chronic renal failure (CRF), the use of
      tuberculin skin test (TST) is controversial. Therefore, determination of the
      factors that affect the TST reactivity would increase the diagnostic value of the
      test. The aim of the present study was to investigate the factors affecting TST
      reactivity and evaluate the relationship between T-lymphocyte subsets and TST
      reactivity. We thus examined 44 patients (mean age 46.6 +/- 15.6 years, 25 males,
      duration of CRF 5.6 +/- 5.2 years), performed TST (an induration with a diameter
      of 5 mm or more was considered as positive) and measured Tlymphocyte subsets and
      biochemical parameters. Twenty-three patients were on hemodialysis, six were on
      peritoneal dialysis, seven were transplant recipients, and eight were on medical
      treatment. Eleven patients (25%) had immunosuppressive treatment. Eleven patients
      (25%) had two, 29 patients (66%) had one, and four patients (9%) had no BCG
      scars. Five patients (11%) had low body mass index (BMI). T-lymphocyte subsets
      were as follows: CD4= 40.7 +/- 7.6%, CD8= 32 +/- 8.9%, CD4/CD8= 1.7 +/- 2.5%,
      CD3= 71.4 +/- 9.4%, CD19= 6.3 +/- 5.1%, NK= 9.7 +/- 5.9. Twenty-two patients had
      positive TST reactivity. No relation was found between TST reactivity and age,
      gender, co-morbidity, BCG vaccination, BMI, immunosuppressive therapy, duration
      and treatment of CRF. Similarly, TST reactivity was not related to the
      biochemical parameters and Tlymphocyte subsets. These data provide that
      tuberculin reactivity does not seem to be associated with T-lymphocyte
      dysfunction and clinical features in patients with chronic renal failure.

PMID- 16615010
TI  - T cell prolymphocytic leukemia: a rare cause of acute liver failure.

PMID- 16615012
TI  - [The importance of contact tracer in detection of childhood and female TB cases;
      a retrospective case-control study in Istanbul].
AB  - We compared age, sex and the forms of disease between the group consisted of
      patients admitted to dispensaries by symptoms and the other group consisted of
      patients found by screening of the contacts. Study covers randomly selected 640
      patients from the group diagnosed by passive methods (P-Tbc) and 419 patients
      from the group diagnosed by active methods (A-Tbc) in Istanbul dispensaries
      between 1999-2000. Data, since 1997 in Istanbul Union against Tbc, were taken
      from the central archives. Of P-Tbc cases, 27% (174/640) was female, 73%(466/640)
      was male. Of A-Tbc cases, 46% (193/419) was female and 54% (226/419) was male (p=
      0.0001). While 3.4% of P-Tbc cases (22/640) was between 0-14 years old, it was
      7.8% (33/419) in the A-Tbc group (p= 0.002). Study shows that screening the
      tuberculosis patients' close contact give us an important numbers of contagious
      cases. It also seems how to increase the female and child tuberculosis patients
      diagnosing.

PMID- 16615013
TI  - The value of serum interferon-gamma level in the differential diagnosis of active
      and inactive pulmonary tuberculosis.
AB  - Interferon (IFN)-gamma plays a pivotal role in protective immunity against
      Mycobacterium tuberculosis. Elevations of IFN-gamma have been found in the
      affected lung and bloodstream of patients with pulmonary tuberculosis. In the
      present study, we aimed to investigate the role of serum IFN-gamma level in the
      differential diagnosis of active and inactive pulmonary tuberculosis. Fourty
      seven patients with newly diagnosed active pulmonary tuberculosis, 21 patients
      with inactive pulmonary tuberculosis, and 20 healthy volunteers were enrolled in
      the study. Serum samples were collected from each subject and stored at - 70
      degrees C until the analysis of IFN-gamma. The mean value of IFN-gamma levels
      were 9.3 +/- 4.6 pg/mL in patients with newly diagnosed pulmonary tuberculosis,
      9.8 +/- 3.8 pg/mL in patients with inactive tuberculosis, and 10.2 +/- 3.4 pg/mL
      in healthy controls. The comparison of IFN-gamma levels of the three groups was
      not found statistically significant (p= 0.4). Serum IFN-gamma level was not found
      to be valuable in the differential diagnosis of active and inactive pulmonary
      tuberculosis.

PMID- 16615014
TI  - [C-reactive protein, leukocyte count and ESR in the assessment of severity of
      community-acquired pneumonia].
AB  - This study aimed to evaluate the relations between the levels of CRP, leukocyte
      count and ESR on admission and the severity of pneumonia according to the
      criteria of Turkish Thoracic Society (TTS) and British Thoracic Society (BTS) CAP
      guidelines. This study included the adult patients with CAP admitted to our
      clinic between the years 2003-2005. The history, physical findings, hemogram,
      ESR, the levels of CRP and the results of other laboratory investigations were
      obtained from the medical records. The patients were grouped according to BTS and
      TTS guidelines. The mean age was 47.2 years; 70 patients (75.3%) were male and 23
      patients (24.7%) were female. The severity of pneumonia according to BTS criteria
      was correlated with the levels of CRP and leukocyte count (p= 0.037, p= 0.01,
      respectively). The severity of pneumonia according to TTS criteria was correlated
      with the levels of CRP, leukocyte count and ESR (p= 0.000, p= 0.014, p= 0.015,
      respectively). Among TTS pneumonia groups, there were statistically significant
      differences between groups 1 and 3; groups 1 and 4; groups 2 and 3 (p= 0.006, p=
      0.041, p= 0.05, respectively) for mean CRP levels. The mean levels of CRP (103.2
      +/- 76.4 mg/L), leukocyte count (19.8 +/- 9.5 x 10(3)/microL) and ESR (57.2 +/-
      26.8 mm/hour) were statistically significantly higher in inpatients than the mean
      levels of CRP (53.2 +/- 52.8 mg/dL), leukocyte count (14.6 +/- 5.4 x
      10(3)/microL) and ESR (43.1 +/- 25.9 mm/hour) in outpatients (p= 0.000, p= 0.001,
      p= 0.012, respectively) according to TTS. It is considered that CRP, a powerful
      marker of inflammation, is related with severity of pneumonia and a high level of
      CRP may be useful to make a decision about hospitalisation.

PMID- 16615015
TI  - [Surgical results of large cell neuroendocrine carcinoma of the lung].
AB  - Large cell neuroendocrine carcinoma is rare in the group of primary lung cancers
      and its appropriate treatment and prognosis are controversial. In this report,
      patients diagnosed as large cell neuroendocrine carcinoma of the lung were
      presented and discussed in the light of pertaining literature. Between February
      1997 and March 2005, eight patients, who were diagnosed as large cell
      neuroendocrine carcinoma postoperatively among the patients with a preoperative
      diagnosis of nonsmall cell lung cancer, were analyzed retrospectively, by means
      of treatment method, disease free survival and overall survival. All eight
      patients were male and their mean age and age range were 64 +/- 7.6 and 50-72,
      respectively. Four patients had lobectomy, two had pneumonectomy and two had
      limited resections. One patient received neoadjuvant chemotherapy and seven
      patients received adjuvant chemotherapy, radiotherapy, or chemoradiotherapy.
      Follow-up period was 19.7 +/- 12.5 (3-39) months and disease-free interval was 19
      +/- 12.9 (3-39) months. Two patients died of recurrence 14 and 16 months
      postoperatively, whereas six of the cases are alive with disease-free. Large cell
      neuroendocrine carcinomas are aggressive tumors with poor prognosis but better
      prognosis is also revealed after surgery at early stages. Most of the series in
      the literature are small in number of patients, as in our report, and treatment
      strategies are tried to be formed according to these data.

PMID- 16615016
TI  - Analysis of patients with hemoptysis in a reference hospital for chest diseases.
AB  - Chest physicians frequently come across with the symptom hemoptysis, an alerting
      symptom which may result from a wide variety of disorders. In this study, we
      aimed to determine the main causes of hemoptysis in a reference hospital for
      chest diseases. All the patients who admitted to our emergency clinic with
      hemoptysis during three months of study period were included in the study. The
      mean age of 143 patients (106 males, 37 females) who were included in this study
      was 48 +/- 17 years. Medical history, physical examination and chest radiography
      were performed for each patient. Sputum examination for acid fast bacilli,
      computed tomography of thorax, fiberoptic bronchoscopy, ventilation-perfusion
      scintigraphy, echocardiography, ear-nose-throat examination and upper
      gastrointestinal system endoscopy were the further diagnostic investigations for
      selected patients. Bronchiectasis was the most common cause of hemoptysis
      (22.4%), followed by lung cancer (18.9%), active tuberculosis (11.2%), and
      inactive tuberculosis (10.5%). Sputum smear for acid fast bacilli was performed
      in 102 patients and were positive in 15.6% of them. Computed tomography of thorax
      was performed in 102 patients and was pathologic in 81.3% of them. Fiberoptic
      bronchoscopy was performed in 46 patients and localized the bleeding site in
      67.4% of them. In conclusion, the most common causes of hemoptysis were
      bronchiectasis, lung cancer and tuberculosis in our hospital. Based on this
      finding, we suggest that, the diagnostic approach to the patients presenting with
      hemoptysis should include first a detailed medical history, physical examination,
      and chest radiography; second sputum smear for acid fast bacilli; third computed
      tomography of thorax and lastly fiberoptic bronchoscopy.

PMID- 16615017
TI  - [Success of smoking cessation in patients with chronic obstructive pulmonary
      disease].
AB  - Smoking causes chronic obstructive pulmonary disease (COPD) in 15 to 20% of
      smokers. Smoking accelerates the annual rate of FEV(1) decline, whereas it was
      demonstrated that smoking cessation is the major factor that reduces this
      decline. The aims of this prospective study were to assess the success rate and
      factors affecting smoking cessation, besides, to evaluate the effect of cessation
      on annual FEV(1) decline. Sixty-five consecutive patients with COPD and as a
      control group 50 ageand sex-matched healthy smokers who were admitted to our
      smoking cessation clinic were enrolled in the study. Intensive behavioral therapy
      alone or with nicotine replacement therapy or bupropion HCL was given to both
      groups and success rate of smoking cessation after one year was assessed. It was
      shown that demographic features of the subjects and the history of COPD had no
      effect on success of smoking cessation. At the end of one year the rate of
      smoking cessation was 29% in patients with COPD and 49% in the control group (p<
      0.05). All different therapy interventions had similar effects on smoking
      cessation. The annual FEV(1) values increased 29 mL in quitters and decreased 25
      mL in patients continuing smoking (p> 0.05). In this study, we concluded that the
      success of smoking cessation in COPD patients admitted to the smoking cessation
      clinic was significantly lower than healthy smokers and annual FEV(1) decline was
      decreased in quitters.

PMID- 16615018
TI  - [The effect of postgraduate education on COPD knowledge level of primary care
      physicians].
AB  - Besides chest disease specialists, primary care physicians also have a great role
      in prevention and treatment of chronic obstructive pulmonary disease (COPD). The
      aim of this study was to evaluate the knowledge levels of primary care physicians
      about COPD before and after post graduate course. The level of knowledge was
      evaluated by a questionnaire including questions about COPD definition,
      prevalence, etiology, pathology, diagnostic methods, physical examination
      findings and treatment. Then a postgraduate course was performed about COPD and
      questionnaire forms were refilled. Ninety two physicians filled the questionnaire
      forms before and after seminar. Fifty of the physicians were female, 42 were
      male, mean age was 33.7 +/- 8.5 and duration of profession was 9.6 +/- 8 years.
      Thirty-six (39.2%) of physicians have attended a post graduate seminar on COPD
      previously. All physicians answered the questions about the most dominant sex
      that COPD was seen and etiologic agents correctly. Most of the physicians
      answered the questions about diseases that defined as COPD, pathology and
      physical examination findings incorrectly. There was no difference in number of
      correct answers between the physicians who have previously attended a post
      graduate seminar or not. Duration of profession was not correlated with correct
      answers. After the seminar, the number of correct answers increased
      significantly. Since most of the physicians answered the questions which are
      quite important in primary care such as COPD definition and physical examination
      findings incorrectly, it is thought that post graduate seminars about COPD should
      be performed more frequently. After the seminar, we observed significant increase
      in correct answers however long-term stability of this knowledge is needed to be
      determined in future studies.

PMID- 16615019
TI  - A relapsing case of Wegener's granulomatosis presenting as an endobronchial mass.
AB  - Wegener's granulomatosis (WG) relapse is frequent. Although lung involvement
      occurs in 85% of patients, endobronchial presentation of the disease is uncommon.
      We reported a relapsing case of WG presenting as an endobronchial mass. A 56-
      year-old man present ed with recurrence of WG following 14 months of
      cyclophosphamide and prednisolone therapy and 36 months of complete remission. At
      his first presentation, he was diagnosed as having WG with involvement of kidney,
      lung, upper airways, skin, joints and eyes. His chest X-ray showed bilateral
      patchy consolidation. Cytoplasmic-anti-neutrophil cytoplasmic antibodies (c-ANCA)
      was also present in high titres. c-ANCA was negative after therapy. At the time
      of relapse, he presented with nasal symptoms and hemoptysis. His chest X-ray
      showed right paracardiac opacity. Fiberoptic bronchoscopy revealed a mass lesion
      subtotally obstructing the proximity of right lower lobe. He has been given
      prednisolone in tapering doses and cyclophosphamide for 10 months.

PMID- 16615020
TI  - Bilateral choroidal metastases as an initial manifestation of small-cell
      carcinoma of the lung.
AB  - The occurrence of clinically symptomatic intraocular metastases as an initial
      manifestation of primary neoplasm is rare event. The recognition of metastatic
      ocular tumors is important since they indicate a poor prognosis. Prompt diagnosis
      and treatment can significantly improve the quality of life for these patients.
      We report the case of a 48-year-old man presenting with a two-week history of
      left sided intraocular pain with blurring of vision and headache, which are the
      first signs of small-cell lung carcinoma.

PMID- 16615021
TI  - Primary pulmonary amyloidosis associated with multiple myeloma.
AB  - Amyloidosis is a syndrome characterized by the deposition of an insoluble
      proteinaceous material in the extracellular matrix of one or several organs.
      Respiratory tract involvement with amyloid is rare and deposition of lower
      respiratory tract has been recognized in a variety of situations with different
      presentations. Primary idiopathic amyloidosis may be a diagnostic problem because
      of its low incidence and its variable manifestations. We report herein a case
      with multiple myeloma presenting diffuse interstitial infiltration, in which
      pulmonary AL type amyloidosis was diagnosed through transbronchial lung biopsy.

PMID- 16615022
TI  - [Pulmonary hyalinizing granuloma mimicking pulmonary carcinoma].
AB  - Pulmonary hyalinizing granuloma is a rare fibrosing nodular disease of the lung
      characterized by solitary or multiple pulmonary nodules. They can occur after
      inflammatory or post-inflammatory changes. A 60 years old asymptomatic patient
      admitted to our clinic because of a solid mass of 6 cm in his routine chest
      radiography. A lobectomy was performed and the histological diagnosis was
      reported as pulmonary hyalinizing granuloma. This case, mimicking pulmonary
      carcinoma, is rarely found in the literature.

PMID- 16615024
TI  - [Effects of air pollution on respiratory health].
AB  - Air pollution, which started to become a serious health concern with industrial
      revolution, has been threatening human health. Epidemiological studies have
      reported a close relation between air pollution and respiratory morbidity and
      mortality. Studies investigating the mechanisms underlying respiratory effects of
      air pollution have reported that pollutants lead to increased respiratory
      symptoms, decreased respiratory function and induce inflammatory changes in
      airways. In vitro studies have demonstrated that air pollutants exert their
      effects by causing cellular injury directly, and indirectly activating
      intracellular oxidative pathways. Air way epithelial cells, which form the first
      line of defence against air pollutants, may play an active role in this
      pathophysiological course.

PMID- 16615023
TI  - [A case of resistant pulmonary and cerebral aspergillosis successfully treated
      with voriconazole].
AB  - Invasive pulmonary aspergillosis (IPA) is the most common fungal pulmonary
      infection in immunocompromised patients. In this disease, it is hard to diagnose,
      it's therapy process is variable and mortality is high. Prognosis is even worse
      in the cases which have cerebral aspergillosis. The patient was following up as a
      diagnosis of usual interstitial pneumonia and treating with corticosteroids and
      azothiopurine. Patient attended our clinic with headache and lose of vision. IPA
      and cerebral aspergillosis was the diagnosis as his examinations. Amphotericin B
      lipid complex treatment were given because of pulmonary and cerebral
      aspergillosis. Voriconazole was the second therapy because of the no response.
      Voriconazole is more effective in cerebral aspergillosis and treated this patient
      successfully.

PMID- 16615025
TI  - [Cardiopulmonary exercise testing].
AB  - The resting pulmonary and cardiac function testing cannot reliably predict
      exercise performance and functional capacity. Cardiopulmonary exercise testing
      (CPET) provides to assessment of the pulmonary, cardiovascular, hematopoietic,
      neuropsychological, and skeletal muscle systems. Thus, CPET has gained increasing
      popularity for the evaluation of undiagnosed exercise intolerance and exercise
      related symptoms, and to reveal functional capacity and impairment.

PMID- 16615026
TI  - [Letter to the editor].

PMID- 16615029
TI  - [Avoiding and dealing with bleeding during endoscopic sinus surgery].
AB  - Endoscopic sinus surgery is one of the most frequent surgical ENT-procedures.
      Bleeding during surgery may increase complications and may have negative effects
      on surgery and outcome. The present paper describes strategies to prevent and
      deal with bleeding during sinus surgery. Preoperative conservative treatment of
      mucosal inflammation as well the use of adrenalin for decongestion may reduce
      intraoperative bleeding and hence complications.

PMID- 16615030
TI  - [Medical indications and effectiveness of the pneumococcal conjugate vaccine].
AB  - Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis,
      sinusitis, and acute otitis media in children and adults worldwide. Especially in
      the age group of < 2 years the incidence of invasive pneumococcal is high. The
      vulnerability of children to S. pneumoniae can also be demonstrated by the high
      rate of sequelae (> 20 % in Germany) and the high mortality (7.5 %) in
      pneumococcal meningitis. A 7-valent pneumococcal conjugate vaccine that was shown
      to be highly efficacious in preventing invasive pneumococcal disease in infants
      in the USA was licensed in Europe in 2001. It is expected that broad usage of the
      vaccine would reduce the incidence of invasive pneumococcal disease and the
      levels of pneumococcal resistance significantly.

PMID- 16615032
TI  - Sensory drive in cichlid speciation.
AB  - The role of selection in speciation is a central yet poorly understood problem in
      evolutionary biology. The rapid radiations of extremely colorful cichlid fish in
      African lakes have fueled the hypothesis that sexual selection can drive species
      divergence without geographical isolation. Here we present experimental evidence
      for a mechanism by which sexual selection becomes divergent: in two sibling
      species from Lake Victoria, female mating preferences for red and blue male
      nuptial coloration coincide with their context-independent sensitivities to red
      and blue light, which in turn correspond to a difference in ambient light in the
      natural habitat of the species. These results suggest that natural selection on
      visual performance, favoring different visual properties in different spectral
      environments, may lead to divergent sexual selection on male nuptial coloration.
      This interplay of ecological and sexual selection along a light gradient may
      provide a mechanism of rapid speciation through divergent sensory drive.

PMID- 16615033
TI  - Does red noise increase or decrease extinction risk? Single extreme events versus
      series of unfavorable conditions.
AB  - Recent theoretical studies have shown contrasting effects of temporal correlation
      of environmental fluctuations (red noise) on the risk of population extinction.
      It is still debated whether and under which conditions red noise increases or
      decreases extinction risk compared with uncorrelated (white) noise. Here, we
      explain the opposing effects by introducing two features of red noise time
      series. On the one hand, positive autocorrelation increases the probability of
      series of poor environmental conditions, implying increasing extinction risk. On
      the other hand, for a given time period, the probability of at least one
      extremely bad year ("catastrophe") is reduced compared with white noise, implying
      decreasing extinction risk. Which of these two features determines extinction
      risk depends on the strength of environmental fluctuations and the sensitivity of
      population dynamics to these fluctuations. If extreme (catastrophic) events can
      occur (strong noise) or sensitivity is high (overcompensatory density
      dependence), then temporal correlation decreases extinction risk; otherwise, it
      increases it. Thus, our results provide a simple explanation for the contrasting
      previous findings and are a crucial step toward a general understanding of the
      effect of noise color on extinction risk.

PMID- 16615034
TI  - The role of local populations within a landscape context: defining and
      classifying sources and sinks.
AB  - The interaction of local populations has been the focus of an increasing number
      of studies in the past 30 years. The study of source-sink dynamics has especially
      generated much interest. Many of the criteria used to distinguish sources and
      sinks incorporate the process of apparent survival (i.e., the combined
      probability of true survival and site fidelity) but not emigration. These
      criteria implicitly treat emigration as mortality, thus biasing the
      classification of sources and sinks in a manner that could lead to flawed habitat
      management. Some of the same criteria require rather restrictive assumptions
      about population equilibrium that, when violated, can also generate misleading
      inference. Here, we expand on a criterion (denoted "contribution" or Cr) that
      incorporates successful emigration in differentiating sources and sinks and that
      makes no restrictive assumptions about dispersal or equilibrium processes in
      populations of interest. The metric Cr is rooted in the theory of matrix
      population models, yet it also contains clearly specified parameters that have
      been estimated in previous empirical research. We suggest that estimates of
      emigration are important for delineating sources and sinks and, more generally,
      for evaluating how local populations interact to generate overall system
      dynamics. This suggestion has direct implications for issues such as species
      conservation and habitat management.

PMID- 16615035
TI  - Individual variation in social aggression and the probability of inheritance:
      theory and a field test.
AB  - Recent theory suggests that much of the wide variation in individual behavior
      that exists within cooperative animal societies can be explained by variation in
      the future direct component of fitness, or the probability of inheritance. Here
      we develop two models to explore the effect of variation in future fitness on
      social aggression. The models predict that rates of aggression will be highest
      toward the front of the queue to inherit and will be higher in larger, more
      productive groups. A third prediction is that, in seasonal animals, aggression
      will increase as the time available to inherit the breeding position runs out. We
      tested these predictions using a model social species, the paper wasp Polistes
      dominulus. We found that rates of both aggressive "displays" (aimed at
      individuals of lower rank) and aggressive "tests" (aimed at individuals of higher
      rank) decreased down the hierarchy, as predicted by our models. The only other
      significant factor affecting aggression rates was date, with more aggression
      observed later in the season, also as predicted. Variation in future fitness due
      to inheritance rank is the hidden factor accounting for much of the variation in
      aggressiveness among apparently equivalent individuals in this species.

PMID- 16615036
TI  - Diagnostics for confounding in PK/PD models for oxcarbazepine.
AB  - One type of pharmacokinetic/pharmacodynamic (PK/PD) relationship that is used to
      characterize the therapeutic action of a drug is the relationship between some
      univariate summary of the plasma-concentration-versus-time profile and the drug
      effect on a response outcome. Operationally, such a relationship may be observed
      in a large clinical trial where randomly sampled patients are randomized to
      different values of the concentration summary. If, under such conditions, the
      relationship between concentration and effect does not depend on the dose needed
      to attain the target concentration, such a relationship will be called a true
      PK/PD relationship. When the true PK/PD relationship is assessed as an object of
      estimation in a dose-controlled clinical trial (i.e. when dose is randomized),
      observed drug concentration is an outcome variable. The estimated PK/PD
      relationship between observed outcome and observed concentration, which we then
      refer to as the conventional PK/PD relationship, may be biased for the true PK/PD
      relationship. Because of this bias, the conventional relationship is called
      confounded for the true one. We show that diagnostics for confounding can be
      devised under reasonable assumptions. We then apply these diagnostics to PK/PD
      assessments of adults and children on oxcarbazepine adjunctive therapy. It was
      necessary to demonstrate the similarity of the true PK/PD relationships of adults
      and children on adjunctive therapy in order to support the approval of
      oxcarbazepine monotherapy in children by a bridging argument.

PMID- 16615037
TI  - The compensating income variation of cardiovascular disease.
AB  - This paper uses longitudinal data from the British Household Panel Survey to
      calculate the compensating income variation (CIV) of cardiovascular disease. It
      is found that the CIV decreases with age and is higher for men than for women.
      For women the estimated CIV is similar to those calculated by Groot et al.
      (2004). For men the estimates are somewhat higher than earlier reported.

PMID- 16615038
TI  - The empirical relationship between community social capital and the demand for
      cigarettes.
AB  - We show that the proportion of community social capital attributable to religious
      groups is inversely and strongly related to the number of cigarettes that smokers
      consume. We do not find overall community social capital or the proportion of
      community social capital attributable to religious groups to be related to the
      overall prevalence of smoking. Using a new validated measure of community social
      capital, the Petris Social Capital Index and three years (1998-2000) of US data
      on 39 369 adults, we estimate a two-part demand model incorporating the following
      controls: community-level fixed effects, price (including excise taxes), family
      income, a smuggling indicator, nonsmoking regulations, education, marital status,
      sex, age, and race/ethnicity.

PMID- 16615039
TI  - Deleting 'irrational' responses from discrete choice experiments: a case of
      investigating or imposing preferences?
AB  - Investigation of the 'rationality' of responses to discrete choice experiments
      (DCEs) has been a theme of research in health economics. Responses have been
      deleted from DCEs where they have been deemed by researchers to (a) be
      'irrational', defined by such studies as failing tests for non-satiation, or (b)
      represent lexicographic preferences. This paper outlines a number of reasons why
      deleting responses from DCEs may be inappropriate after first reviewing the
      theory underpinning rationality, highlighting that the importance placed on
      rationality depends on the approach to consumer theory to which one ascribes. The
      aim of this paper is not to suggest that all preferences elicited via DCEs are
      rational. Instead, it is to suggest a number of reasons why it may not be the
      case that all preferences labelled as 'irrational' are indeed so. Hence, deleting
      responses may result in the removal of valid preferences; induce sample selection
      bias; and reduce the statistical efficiency and power of the estimated choice
      models. Further, evidence suggests random utility theory may be able to cope with
      such preferences. Finally, we discuss a number of implications for the design,
      implementation and interpretation of DCEs and recommend caution regarding the
      deletion of preferences from stated preference experiments.

PMID- 16615040
TI  - Effect of serotonin-acting agents on the serotonin content of immune cells. A
      peculiar observation.
AB  - The effect of the tryptophan hydroxylase inhibitor, PCPA methylester, the
      serotonin reuptake inhibitor fluoxetine and MAO-A inhibitor clorgyline on the
      serotonin content of rat immune cells was studied, using labelled antibodies and
      flow cytometry. Each molecule significantly increased in males the serotonin
      concentration of peritoneal lymphocytes and the monocyte-macrophage-granulocyte
      group (mo-gran), however the agents were ineffective towards mast cells. In
      females fluoxetine and clorgyline increased the serotonin concentration in
      peritoneal lymphocytes and mo-gran. Fluoxetine also increased the serotonin level
      in mast cells. Thymus was absolutely resistant to the drugs in both genders. The
      results call attention (1) to the reverse effect of serotonin-acting agents on
      immune cells, (2) to the influence of the milieu where the cell is located and
      (3) the effect of gender.

PMID- 16615041
TI  - Matrix metalloproteinase-9,-3 and tissue inhibitor of matrix metalloproteinase-1
      in colorectal cancer: relationship to clinicopathological variables.
AB  - The balance between matrix metalloproteinases (MMPs) and their physiological
      tissue inhibitors of matrix metalloproteinases (TIMPs) is crucial in tumour
      invasion and progression. The aim of this study was to investigate the levels of
      MMP-9, MMP-3 and TIMP-1 in colorectal cancer (CRC) and to evaluate these
      proteinases and their inhibitor with respect to clinicopathological variables.
      Activities of pro- and active MMP-9 were measured in paired tumour and distant
      normal tissue specimens from 43 patients with CRC using gelatin zymography. ELISA
      was employed for the determination of MMP-9, MMP-3 and TIMP-1 protein
      expressions. The activity levels of pro- and active MMP-9 and protein expression
      levels of MMP-9, MMP-3 and TIMP-1 were higher in tumour tissues than in the
      corresponding normal tissues; the differences being significant for all (p <
      0.05), except TIMP-1. Similarly, active MMP-9/proMMP-9 and the ratio of protein
      expression level of MMP-9-TIMP-1 were found to be significantly higher in tumour
      tissues ( p < 0.01). Among all the clinicopathological variables investigated,
      significant correlations were found between MMP-9 and presence of perineural
      invasion, MMP-3 and lymph node status, TIMP-1 and tumour differentiation, MMP
      9/TIMP-1 ratio and histological types ( p < 0.05). In conclusion, MMP-3 was not
      as notably increased as MMP-9 in tumour tissues. However, different roles may be
      attributed to MMP-9 and MMP-3 in CRC development and progression. Additionally,
      assessment of TIMP-1 in relation to MMPs appeared to be crucial in CRC studies to
      provide a basis for the re-evaluation of the clinical usefulness of TIMP-1 in
      colorectal cancer.

PMID- 16615042
TI  - The effect of resveratrol on surgery-induced peritoneal adhesions in an
      experimental model.
AB  - Adhesion formation is a common cause of complications following surgery. The aim
      of this study was to investigate the effect of resveratrol on intra-abdominal
      adhesion prevention in a rat model. Twenty one Wistar-Albino rats weighing 200
      250 g were assigned to three groups, of 7 rats each. After a midline laparotomy
      was performed, a 1 cm area of the ceacum was abraded in two of the groups. They
      were then given either resveratrol (Group 1), or saline (Group 2)
      intraperitoneally. Group 3 rats (sham operation) received no treatment, without
      the serosal damage. On the 14th day, the rats were killed and the adhesion score
      was determined according to Mazuji's adhesion grade scale. The tissue levels of
      malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were
      measured. The mean Mazuji's adhesion grade in the resveratrol group was 1.0 +/-
      0.0, in the saline group 2.57 +/- 1.51, and zero in the sham operated group (p <
      0.05 between the resveratrol group and saline group comparison). The levels of
      MDA and NO in the resveratrol group were significantly lower than those of the
      saline group (p < 0.001). The level of GSH in the resveratrol group was
      significantly higher than in the saline and sham operated groups (p < 0.001 and p
      < 0.001, respectively). Introduction of resveratrol into the peritoneal cavity at
      the time of surgery reduced adhesion formation effectively in this model.
      Resveratrol probably acts through reduction of lipid peroxidation products.

PMID- 16615043
TI  - Transmembrane signaling through phospholipase C-beta in the developing human
      prefrontal cortex.
AB  - To investigate changes in muscarinic receptor-stimulated phospholipase C-beta
      (PLC-beta) activity during brain development, we examined the functional coupling
      of each of the three major protein components of the phosphoinositide system (M1,
      M3, and M5 muscarinic receptor subtypes; Gq/11 proteins; PLC-beta1-4 isoforms) in
      membrane preparations from post-mortem human prefrontal cerebral cortex collected
      at several stages of prenatal and postnatal development. In human prenatal brain
      membranes, PLC was found to be present and could be activated by calcium, but the
      ability of guanosine-5'-o-3 thiotriphosphate (GTPgammaS) or carbachol (in the
      presence of GTPgammaS) to modulate prenatal PLC-beta was significantly weaker
      than that associated with postnatal PLC-beta. Western blot analysis revealed that
      the levels of Galphaq/11 did not change significantly during development. In
      contrast, dramatically higher levels of expression of PLC-beta1-4 isoforms and of
      M1, M3, and M5 muscarinic receptors were detected in the child vs. the fetal
      brain, a finding that might underlie the observed increased activity of PLC.
      Thus, inositol phosphate production may be more efficiently regulated by altering
      the amount of effectors (PLC-beta1-4) and receptors (M1,3,5 subtypes) than by
      altering the level of Galphaq/11 subunits. These results demonstrate that
      different PLC isoforms are expressed in the prefrontal cortex of the developing
      human brain in an age-specific manner, suggesting specific roles not only in
      synaptic transmission but also in the differentiation and maturation of neurons
      in the developing brain.

PMID- 16615044
TI  - Moyamoya syndrome following childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: Long-term survivors of childhood acute lymphoblastic leukemia (ALL)
      sometimes suffer from adverse long-term sequelae. We analyzed the incidence,
      clinical course and prognosis of moyamoya syndrome (MoS) following childhood ALL.
      PROCEDURE: A total of 1,846 ALL patients were treated with four consecutive TCCSG
      ALL protocols (L84-11, L89-12, L92-13, and L95-14) between 1984 and 1999. We
      surveyed the MoS cases among these patients in the follow-up studies. RESULTS:
      Six patients with MoS were identified: four boys and two girls whose ages ranged
      from 2 years and 1 month (abbreviated as "2y1m") to 14y 1 m at diagnosis of ALL.
      None of the patients had central nervous system (CNS) leukemia. All six patients
      received prophylactic cranial irradiation with a dosage of 18 or 24 Gy. Although
      one patient died of brain infarction due to MoS, no leukemic relapse was observed
      in the group. The cumulative incidence of MoS in our series was 0.46 +/- 0.02% at
      8 years. Among several clinical characteristics, use of cranial irradiation was
      the only factor that appeared to be significantly related to the development of
      MoS. CONCLUSIONS: MoS occurs with increased frequency in children treated for
      ALL, and might be associated with cranial irradiation. Prophylactic cranial
      irradiation should be used cautiously in ALL patients who can be cured by other
      CNS-directed therapies.

PMID- 16615045
TI  - Neuregulin isoforms in dorsal root ganglion neurons: effects of the cytoplasmic
      domain on localization and membrane shedding of Nrg-1 type I.
AB  - Embryonic sensory neurons express membrane-anchored growth factors that stimulate
      proliferation and differentiation of Schwann cells. The most important of these
      are members of the neuregulin-1 (Nrg-1) family that activate the erbB2/erbB3
      receptor kinase on Schwann cells. Nrg-1 growth factors display a complex pattern
      of alternative mRNA splicing. We investigated the expression of the Nrg-1 type I
      in rat embryo dorsal root ganglion (DRG) neurons. Nrg-1 type I mRNA was
      abundantly expressed in DRG neurons; molecular cloning identified three distinct
      isoforms. The most prominent structural difference produced by alternative
      splicing was truncation of the C-terminal cytoplasmic domain. In sensory neurons
      and other cells, Nrg-1 type I proteins with the full-length 374-amino-acid
      cytoplasmic domain were expressed on the cell surface. In contrast, an isoform
      with a partially truncated cytoplasmic domain was retained in an intracellular
      compartment. Deletion studies demonstrated the presence of a cryptic
      intracellular retention signal that was exposed in the truncated cytoplasmic
      domain. Cell surface Nrg-1 type I molecules were subject to protease-dependent
      release of the biologically active ectodomain. As a consequence of their
      intracellular localization, the Nrg-1 type I isoform with a truncated cytoplasmic
      domain was not subject to membrane shedding. Nrg-1 type I ectodomain release was
      accelerated by factors present in Schwann cell-conditioned medium. In cells with
      active Nrg-1 type I ectodomain, shedding products corresponding to the
      cytoplasmic domain were not detected, because of rapid gamma-secretase- and
      proteasome-dependent degradation. These results demonstrate that sensory neurons
      express alternatively spliced neuregulin polypeptides with distinct subcellular
      localizations and processing.

PMID- 16615046
TI  - Correlation between glucocorticoid receptor binding parameters, blood pressure,
      and body mass index in a healthy human population.
AB  - Correlation between the glucocorticoid receptor (GR) number and affinity for the
      ligand, as well as the relationship between these equilibrium binding parameters
      and body mass index, blood pressure, and age were examined in peripheral blood
      mononuclear cells (PBMC) of healthy human subjects. It was found that the only
      statistically significant correlation was that between the GR number per cell and
      equilibrium dissociation constant, K(d) (r = 0.84, p < 0.0001). This observation
      implies the existence of a compensatory mechanism providing for lower GR affinity
      in individuals that have more receptor sites in circulating mononuclear cells and
      vice versa. This compensatory phenomenon together with considerable
      interindividual variation (GR number per cell ranging from 1391 to 15133, CV =
      58.62%; and K(d) from 2.5 to 98.6 nM, CV = 80.87%), reflects plasticity of the
      glucocorticoid system. The results pose the question of whether this compensatory
      mechanism observed in healthy human subjects persists in pathophysiological
      states associated with glucocorticoid hormone actions and suggest that tissue
      sensitivity to glucocorticoids could be better predicted by the sign and
      magnitude of the correlation between the two receptor equilibrium binding
      parameters than by each of them separately.

PMID- 16615047
TI  - Flash-echo contrast sonography in the evaluation of response of small
      hepatocellular carcinoma to percutaneous ablation.
AB  - PURPOSE: To evaluate the use of flash-echo contrast sonography (FECS) in
      subtraction mode in assessing small hepatocellular carcinoma (HCC) after
      percutaneous local ablation therapy. METHODS: Between March 2000 and February
      2002, we prospectively assessed small HCCs after percutaneous local ablation
      therapy using FECS in subtraction mode. Thirty-three patients (22 men, 11 women)
      with 35 tumors ranging in size from 1.1 to 3.0 cm (mean +/- SD, 2.0 +/- 0.5) were
      enrolled. Twenty-one tumors received percutaneous ethanol injection only, 13
      tumors received percutaneous microwave ablation therapy only, and the remaining
      tumor received both treatments. CT, hepatic angiography, and follow-up were used
      as gold standards in analyzing the accuracy of FECS in detecting residual tumors.
      RESULTS: The agreements between FECS and CT, FECS and hepatic angiography, and
      all 3 imaging modalities were 80% (28/35), 85.7% (30/35), and 77.1% (27/35),
      respectively. Twenty-one patients with 23 completely ablated tumors were followed
      up for 5 to 39 months (mean +/- SD, 20.2 +/- 11.2). Recurrent disease was
      detected in 11 (52.4%) patients; local tumor recurrence occurred in 4 (17.4%)
      patients. The sensitivity, specificity, accuracy, and positive and negative
      predictive value of FECS in detecting viable tumors were 53.8% (7/13), 90.9%
      (20/22), 77.1% (27/35), 77.8% (7/9), and 76.9% (20/26), respectively.
      CONCLUSIONS: FECS in subtraction mode shows good agreement with hepatic
      angiography and CT in the assessment of small HCC after percutaneous local
      ablation therapy. The sensitivity of FECS in detecting residual tumors is
      suboptimal.

PMID- 16615048
TI  - Delineation of brain tumor margins using intraoperative sononavigation:
      implications for tumor resection.
AB  - PURPOSE: Sonography has been employed for real-time intraoperative delineation of
      tumor boundaries during resection of brain tumors. However, the variably
      hyperechoic appearance of brain edema or gliosis surrounding the brain may
      interfere with accurate depiction of tumor margins. The goal of the present study
      was to use sononavigation, which provides coregistration between real-time
      sonograms and MRI scans, to assess the accuracy of sonographic determination of
      tumor margins. METHODS: Sononavigation was performed on 12 brain tumors (7
      metastatic brain tumors, 2 meningiomas, 1 anaplastic oligodendroglioma, 1
      anaplastic pilocytic astrocytoma, and 1 anaplastic astrocytoma). Sonograms of
      tumor margins were categorized into 1 of 3 types: in type 1, the tumor margin was
      clearly visualized and corresponded to the margin of the enhanced lesion on MR
      scan in all areas; in type 2, the tumor margin was clearly seen in some areas but
      was obscure in others due to hyperechoic edema; and in type 3, the tumor margin
      was indistinguishable from surrounding tissues in all areas. RESULTS: Three
      metastatic brain tumors and 1 meningioma were categorized as type 1. Three
      metastatic brain tumors, 1 meningioma, and 1 anaplastic oligodendroglioma were
      categorized as type 2. The anaplastic pilocytic astrocytoma, 1 metastatic brain
      tumor (which consisted mainly of necrotic tissue), and the anaplastic astrocytoma
      were categorized as type 3. These data assist in determining whether the
      sonographic appearance of tumor margins is accurate and whether to rely on
      information from either sonography (type 1) or the sononavigation system when
      resecting tumor types 1, 2, and 3. CONCLUSIONS: Sononavigation can help
      categorize the sonographic tumor margins into 3 different patterns, and this
      categorization can assist in determining which imaging modalities are needed to
      better delineate the tumor margins for subsequent resection.

PMID- 16615049
TI  - Sonographic diagnosis of toddler's fracture in the emergency department.
AB  - We describe 3 cases of toddler's fracture of the tibia that were diagnosed via
      sonographic examination. In cases, initial radiographs did not show the fracture,
      whereas sonographic examination revealed a layer of low reflectivity superficial
      to the tibial cortex and an elevated periosteum, suggesting a fracture hematoma.
      The diagnosis was confirmed at 2-3 weeks with radiographs demonstrating
      periosteal reaction. Both fractures were treated with cast immobilization for 4
      weeks and made a full recovery. The third case was diagnosed via sonography and
      was confirmed by the initial radiographs. These results strongly suggest that
      sonography can detect the presence of a fracture hematoma and thus may help
      diagnose this injury earlier.

PMID- 16615050
TI  - Hydromediastinum associated with a peripherally inserted central venous catheter
      in a newborn infant.
AB  - We report a case of hydromediastinum in a newborn associated with a peripherally
      inserted central venous catheter. A 9-day-old male infant with total parenteral
      nutrition via a peripherally inserted central venous catheter had acute
      respiratory distress. A chest radiograph showed a widened mediastinal shadow and
      left pleural effusion, and sonography revealed fluid collection in the
      mediastinum and bilateral hydrothorax. Sonography is useful in the diagnosis of
      hydromediastinum when infants treated with peripherally inserted central venous
      catheters have acute respiratory distress.

PMID- 16615051
TI  - Sonographic and mammographic appearances of granular cell tumors of the breast
      with pathological correlation.
AB  - PURPOSE: To describe the sonographic and mammographic appearance of granular cell
      tumors (GCTs) of the breast in 6 patients with pathological correlation. METHODS:
      A search was conducted of the cyto-histopathological database in a single
      institution from 1990 to 2004 for breast lesions given the diagnosis of GCT of
      the breast. Six patients with GCT of the breast who underwent mammographic or
      sonographic examination or both before surgery were included in this study.
      RESULTS: The mammographic features of GCT of the breast were indeterminate in
      most patients, often presenting as an isodense mass with indistinct or spiculated
      margins. Calcifications were not a feature. The sonographic features of GCT of
      the breast mimicked carcinoma, including heterogeneous echotexture, indistinct
      margins, and hypervascularity. Hyperechogenicity was noted in 5 of 7 (71%) GCTs
      in this series. The cytomorphological features of GCT included sheets of large
      granular cells intersected by arborizing thin-walled blood vessels. The cells had
      round to oval nuclei, inconspicuous nucleoli, and abundant, ill-defined granular
      cytoplasm. CONCLUSIONS: Breast imagers should be aware that GCT of the breast is
      an uncommon differential in a minority of neoplasms that can be mistaken for
      breast cancer.

PMID- 16615052
TI  - Sonographic findings of mesenteric panniculitis: correlation with CT and
      literature review.
AB  - PURPOSE: To evaluate the sonographic findings of mesenteric panniculitis (MP) and
      correlate them with CT findings. METHODS: We retrospectively evaluated the
      clinical, CT, and sonographic findings in 26 cases of MP in our hospital between
      January 1997 and July 2003. We also reviewed the sonographic features of MP
      previously described in the literature. RESULTS: The sonographic findings were
      well correlated to CT in 24 of 26 patients (92%). In these 24 cases, abdominal
      sonographic examination revealed a hyperechogenic, well-defined fatty mass
      (corresponding to the pseudocapsule CT sign) in the root of the mesentery,
      displacing the bowel loops. We found a clear interface between MP and normal
      intra abdominal fat. Examination with color Doppler sonography revealed the
      nondeviated mesenteric vessels within the mass. The persence of MP improved
      sonographic transmission in 9 obese patients and enabled the retroperitoneal
      vessels to be clearly visualized. Sonography was unable to demonstrate the
      preservation of the fat nearest the mesenteric vessels corresponding to the
      "fatty halo" sign on CT. CONCLUSIONS: Sonography is useful in the diagnostic
      workup for MP. The characteristic sonographic features of MP (well-defined mass,
      homogeneous hyperechogenicity of the mass, nondeviated vessels within the mass,
      and displaced bowel loops) correlate well with CT findings.

PMID- 16615053
TI  - Accuracy of sonographic volume measurements of kidney transplant.
AB  - PURPOSE: Sonographic measurement of renal volume is one of the parameters used in
      the diagnosis of renal transplant dysfunction and in follow-up of patients with
      renal transplant. The aim of this study was to compare the prolate ellipsoid
      formula with a new formula in calculating the volume of a transplanted kidney.
      METHODS: The renal volumes in 24 patients with a stable renal transplant were
      determined sonographically with the ellipsoid formula and via helical CT with the
      voxel-count method, which is the gold standard. A new formula that uses renal
      length and the cross-sectional area at the maximum transverse section has been
      evaluated in a small series of transplanted kidneys. RESULTS: Renal volume was
      underestimated with the sonographic ellipsoid formula and the new formula. The
      new formula yielded the lowest underestimation of the mean renal volume, and the
      measurements obtained with it were not significantly different from those
      obtained with CT. CONCLUSIONS: The use of sonography is appropriate for accurate
      calculation of renal volume, and the new formula that uses only 2 ultrasound
      parameters best represents the volume of a renal transplant.

PMID- 16615054
TI  - Choledochocele demonstrated on conventional sonography.
AB  - Choledochocele is the least common form of choledochal cyst. We report a rare
      bile duct cyst diagnosed in a 63-year-old woman via CT cholangiography. Although
      conventional sonography initially failed to reveal abnormal findings, a
      subsequent detailed study clearly depicted the lesion. To the best of our
      knowledge, this is the first report of choledochocele unambiguously demonstrated
      on transabdominal sonography.

PMID- 16615055
TI  - Heterotopic pancreas presenting as gastric submucosal cyst on endoscopic
      sonography.
AB  - A 50-year-old Chinese woman with vague epigastric discomfort underwent upper
      gastrointestinal endoscopy that revealed a saddle-shaped submucosal tumor in the
      antrum along the greater curvature. Endoscopic sonography showed that the tumor
      consisted of two cystic lesions. Because of persisting symptoms, the tumor was
      resected 8 months later. Pathological examination revealed scattered heterotopic
      pancreatic acini and ducts in the submucosa and muscularis propria. We suggest
      that heterotopic pancreas, though rare, should be considered in the differential
      diagnosis of cystic lesions of the gastric wall.

PMID- 16615056
TI  - Sonographic diagnosis of an arterioarticular fistula following knee
      arthrocentesis.
AB  - An arterioarticular fistula is an unusual complication of knee arthrocentesis. We
      describe the sonographic findings immediately following a failed clinical attempt
      at knee arthrocentesis that resulted in an arterioarticular fistula. Spectral
      Doppler analysis confirmed the jet of blood into the hemarthrosis. Knowledge of
      anatomy and application of standard technique is necessary to minimize the
      complications of arthrocentesis.

PMID- 16615057
TI  - Time-course of lipid peroxidation in different organs of mice treated with Echis
      pyramidum snake venom.
AB  - This study examined the effect of Echis pyramidum (EP) venom on time-course of
      lipid peroxidation in different vital organs of mice. Adult male Swiss albino
      mice were injected with EP venom (2 mg/kg, i.p.); control mice received vehicle
      alone (normal saline). Mice were killed at 1, 3, 6, 12, and 24 h post
      envenomation. The liver, lung, kidney, heart, and brain (cerebrum and cerebellum)
      were collected for the estimation of malondialdehyde (MDA), an index of lipid
      peroxidation. The results of this study showed that a single injection of EP
      venom caused a significant lipid peroxidation in all the organs studied. The
      onset of lipid peroxidation was as early as 1 h and persisted for several hours,
      suggesting an important role of oxidative stress in the cytotoxicity of EP venom.

PMID- 16615058
TI  - Effects of continuous and intermittent exposure to RF fields with a wide range of
      SARs on cell growth, survival, and cell cycle distribution.
AB  - To examine the biological effects of radio frequency (RF) electromagnetic fields
      in vitro, we have examined the fundamental cellular responses, such as cell
      growth, survival, and cell cycle distribution, following exposure to a wide range
      of specific absorption rates (SAR). Furthermore, we compared the effects of
      continuous and intermittent exposure at high SARs. An RF electromagnetic field
      exposure unit operating at a frequency of 2.45 GHz was used to expose cells to
      SARs from 0.05 to 1500 W/kg. When cells were exposed to a continuous RF field at
      SARs from 0.05 to 100 W/kg for 2 h, cellular growth rate, survival, and cell
      cycle distribution were not affected. At 200 W/kg, the cell growth rate was
      suppressed and cell survival decreased. When the cells were exposed to an
      intermittent RF field at 300 W/kg(pk), 900 W/kg(pk) and 1500 W/kg(pk) (100
      W/kg(mean)), no significant differences were observed between these conditions
      and intermittent wave exposure at 100 W/kg. When cells were exposed to a SAR of
      50 W/kg for 2 h, the temperature of the medium around cells rose to 39.1 degrees
      C, 100 W/kg exposure increased the temperature to 41.0 degrees C, and 200 W/kg
      exposure increased the temperature to 44.1 degrees C. Exposure to RF radiation
      results in heating of the medium, and the thermal effect depends on the mean SAR.
      Hence, these results suggest that the proliferation disorder is caused by the
      thermal effect.

PMID- 16615059
TI  - Methodology of detailed dosimetry and treatment of uncertainty and variations for
      in vivo studies.
AB  - Detailed and accurate dosimetric information is a basic precondition for
      acquiring adequate interpretations and valuations of in vivo studies testing
      radiofrequency (RF) electromagnetic fields (EMF). Instantaneous locally induced
      fields depend on many parameters, for example, orientation of the animal with
      respect to the incident field, animal size and posture, and tissue distribution.
      These parameters are often constrained, resulting in significant uncertainties in
      the dosimetric assessment of the exposure, averaged over all animals and the
      entire experimental phase, as well as in significant variations of the local
      exposures during the experiment. A sufficient analysis should therefore include
      (1) average and peak spatial specific absorption rate (SAR) values for the whole
      body and specific organs, (2) the uncertainty of each assessed SAR value, and (3)
      the short term and long term SAR variations between the tissues of individual
      animals. A methodology to obtain this pertinent information is developed and
      proposed in this paper. Using this methodology the dosimetry of a rat exposure
      apparatus operating at the carrier frequency of 1747 MHz, previously developed
      for a 2-year bioassay study within the European Union project PERFORM, was
      obtained. We have demonstrated that comprehensive dosimetric data can be obtained
      with reasonable effort using the proposed method, providing that the exposure
      setup is soundly formulated.

PMID- 16615060
TI  - Recessive Parkinson's disease.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disease caused by
      loss of dopaminergic neurons in the substantia nigra pars compacta. Although the
      etiology of PD remains unclear, it is now clear that genetic factors contribute
      to the pathogenesis of the disease. Recently, several causative genes have been
      identified in monogenic forms of PD. Accumulating evidence indicates that their
      gene products play important roles in mitochondrial function, oxidative stress
      response, and the ubiquitin-proteasome system, which are also implicated in
      sporadic PD, suggesting that these gene products share a common pathway to nigral
      degeneration in both familial and sporadic PD. Here, we review recent advances in
      knowledge about genes associated with recessive PD, including parkin, PINK1, and
      DJ-1.

PMID- 16615061
TI  - Intracerebral hematoma as a complication of intrathecal methotrexate
      administration.
AB  - Neurotoxicity of methotrexate is a well-documented issue, but development of an
      intracerebral hematoma following administration of intrathecal methotrexate is an
      extremely rare entity. A 6-year-old male with the diagnosis of non-Hodgkin
      lymphoma was put on a treatment regimen, including intrathecal methotrexate. Six
      days following the last intrathecal methotrexate administration, the patient
      developed a deteriorating state of consciousness. There was no history of trauma.
      Coagulation studies and platelet count were normal. Magnetic resonance imaging of
      the brain demonstrated a large left frontoparietal hematoma. Intracerebral
      hematoma may be a very rare, but serious, complication of intrathecal
      methotrexate administration.

PMID- 16615062
TI  - A survey of language barriers from the perspective of pediatric oncologists,
      interpreters, and parents.
AB  - BACKGROUND: Oncologists in the US increasingly face the challenge of
      communicating with non-English speaking parents of children with cancer. This
      study explores this challenge from the perspectives of a sample of pediatric
      oncologists, interpreters, and Spanish-speaking parents of children with newly
      diagnosed leukemia. PROCEDURE: Thirty-seven oncologists and 17 professional
      language interpreters based at two non-profit pediatric hospitals in the US were
      surveyed on the topic of language barriers in pediatric care. Seventeen parents
      who communicated with their child's oncologist through an interpreter were also
      surveyed. RESULTS: All groups expressed considerable concern over the process of
      communicating across a language barrier. For oncologists, these concerns included
      the accuracy and completeness of interpretations, complexity of information, and
      loss of confidence and control over the communication process. For interpreters,
      they included complexity of information, information overload, and lack of
      clinician sensitivity toward the cultural and socioeconomic backgrounds of
      limited English proficiency (LEP) families. Parent concerns included difficulties
      comprehending information and anxiety over the possibility of missing out on
      important information. All groups provided multiple suggestions for improving
      communication across a language barrier. CONCLUSIONS: Oncologists, interpreters,
      and parents expressed considerable concern over the process of communicating
      across a language barrier. Some of these concerns could be minimized through
      efforts to boost interpreter accuracy and completeness, including the use of more
      simple, easy to understand language. Other issues, such as differences in culture
      and socioeconomic background, warrant consideration of the intercultural
      knowledge and skills of interpreters.

PMID- 16615063
TI  - Confocal laser scanning microscopy as a tool for imaging cancellous bone.
AB  - Understanding the bimodal structure of cancellous bone is important for tissue
      engineering in order to more accurately fabricate scaffolds to promote bone
      ingrowth and vascularization in newly forming bone. In this study, confocal laser
      scanning microscopy (CLSM) was used to create detailed images of the bimodally
      porous intertrabecular space of defatted and deproteinized cancellous canine bone
      taken from the epiphysis of the humerus. The bimodal pore structure was imaged
      using both reflective and fluorescent modes in CLSM, resulting in four different,
      but complementary image types: (1) a Z-stack overlay, (2) a phi-Z scan, (3) a
      topographical map, and (4) a contour map. Submerging the bone in rhodamine B dye
      prior to fluorescent imaging enhanced the pore surface details, giving a more
      accurate pore size measurement. The average macropore diameter was found to be
      260 +/- 97 microm while the average micropore diameter was 13 +/- 10 microm. When
      compared with common techniques, including microcomputed tomography, magnetic
      resonance imaging, scanning electron microscopy, and environmental scanning
      electron microscopy, for imaging cancellous bone, CLSM was found to be an
      effective tool, given its ability to nondestructively image the surface and near
      surface pore structure.

PMID- 16615064
TI  - Embryonic and larval expression of zebrafish voltage-gated sodium channel alpha
      subunit genes.
AB  - Whereas it is known that voltage-gated calcium channels play important roles
      during development, potential embryonic roles of voltage-gated sodium channels
      have received much less attention. Voltage-gated sodium channels consist of pore
      forming alpha-subunits (Na(v)1) and auxiliary beta-subunits. Here, we report the
      embryonic and larval expression patterns for all eight members of the gene family
      (scna) coding for zebrafish Na(v)1 proteins. We find that each scna gene displays
      a distinct expression pattern that is temporally and spatially dynamic during
      embryonic and larval stages. Overall, our findings indicate that scna gene
      expression occurs sufficiently early during embryogenesis to play developmental
      roles for both muscle and nervous tissues.

PMID- 16615065
TI  - Movement disorders associated with hyperthyroidism: expanding the phenotype.

PMID- 16615066
TI  - Cross-relaxation bottleneck in water-lysozyme proton magnetization exchange.
AB  - The proton spin-lattice relaxation parameters in natural and deuterated lysozyme
      solutions have been measured as a function of temperature (0-50 degrees C). The
      variation of the apparent magnitudes of the water proton magnetizations in the
      solutions with temperature indicates that magnetic coupling mixes protein and
      water proton magnetizations. The results are consistent with an exchange cross
      relaxation model (Hills, B. P., Mol Phys 1992, 76, 489-508) in which the cross
      relaxation acts between the labile and nonlabile protons, rather than between
      water and protein protons. Although this cross-relaxation pathway clearly affects
      the observed magnetization fractions in this protein solution, its influence on
      the relaxation rates is less apparent.

PMID- 16615067
TI  - Examination of surface properties and in vitro biological performance of
      amorphous diamond-like carbon-coated polyurethane.
AB  - Despite the emerging use of diamond-like carbon (DLC) as a coating for medical
      devices, few studies have examined the resistance of DLC coatings onto medical
      polymers to both microbial adherence and encrustation. In this study, amorphous
      DLC of a range of refractive indexes (1.7-1.9) and thicknesses (100-600 nm) was
      deposited onto polyurethane, a model polymer, and the resistance to microbial
      adherence (Escherichia coli; clinical isolate) and encrustation examined using in
      vitro models. In comparison to the native polymer, the advancing and receding
      contact angles of DLC-coated polyurethane were lower, indicating greater
      hydrophilic properties. No relationship was observed between refractive index,
      thickness, and advancing contact angle, as determined using multiple correlation
      analysis. The resistances of the various DLC-coated polyurethane films to
      encrustation and microbial adherence were significantly greater than that to
      polyurethane; however, there were individual differences between the resistances
      of the various DLC coatings. In general, increasing the refractive index of the
      coatings (100 nm thickness) decreased the resistance of the films to both
      hydroxyapatite and struvite encrustation and to microbial adherence. Films of
      lower thicknesses (100 and 200 nm; of defined refractive index, 1.8), exhibited
      the greatest resistance to encrustation and to microbial adherence. In
      conclusion, this study has uniquely illustrated both the microbial antiadherence
      properties and resistance to urinary encrustation of DLC-coated polyurethane. The
      resistances to encrustation and microbial adherence were substantial, and in
      light of this, it is suggested that DLC coatings of low thickness and refractive
      index show particular promise as coatings of polymeric medical devices.

PMID- 16615068
TI  - Effect of light-curing method on marginal adaptation, microleakage, and
      microhardness of composite restorations.
AB  - The objective of this study was to investigate the effects of different light
      curing methods on microleakage, marginal adaptation, and microhardness of
      composite restorations. Slot-type preparations were made in bovine teeth, with
      gingival margins on dentin. Specimens were divided into 12 groups (n = 12)
      according to composite-light-curing unit (LCU) combinations. Three composites
      were used: Filtek Supreme, Herculite XRV, and Heliomolar. All restorations were
      placed using the same adhesive. Four LCUs were used: a quartz-tungsten-halogen
      (QTH) LCU (Optilux 501), a first-generation light-emitting diode (LED) LCU
      (FreeLight 1), and two second-generation LED LCUs (FreeLight 2 and Translux Power
      Blue). After finishing and polishing, specimens were subjected to mechanical load
      cycling (100,000 cycles). Gingival margin adaptation was determined as a function
      of gap formation using epoxy replicas. Microleakage was evaluated by measuring
      dye penetration across the gingival wall in cross-sectioned specimens.
      Microhardness was measured as Knoop Hardness number (KHN) at different occluso
      gingival locations in cross-sectioned specimens. Data were analyzed for
      statistical significance (p = 0.05) using appropriate statistical tests. Marginal
      adaptation was affected by load-cycling in most specimens, but no significant
      differences were observed among composites and LCUs. Microleakage was not
      affected by LCU, except for Heliomolar specimens which when cured with Optilux
      501 resulted in higher microleakage scores than those obtained with the other
      LCUs. For microhardness, Translux Power Blue generally produced the highest
      values and the FreeLight 1 produced the lowest. The performance of the second
      generation LED LCUs generally was similar to that of the QTH control, and better
      than that of the first-generation LED unit.

PMID- 16615069
TI  - Fine ceramic lattices prepared by extrusion freeforming.
AB  - Fine ceramic lattices with spatial resolution <100 microm and having precise
      dimensions and intricate hierarchical structure are fabricated by extrusion
      freeforming, a rapid prototyping technique, which allows overall shape and
      structure to be controlled by computer. The procedure can be used for any fine
      ceramic powder and can therefore find applications as diverse as microwave and
      terahertz metamaterials (artificial crystals), hard tissue scaffolds,
      microfluidic devices, and metal matrix composite preforms. The examples presented
      here are calcium phosphate lattices with three structure levels: submicron pores,
      which enhance cell-surface interactions, pores of tens of microns to encourage
      bone ingrowth, and corridors (hundreds of microns) for vascularization. With
      controlled pore structures on these scales, the lattices are expected to provide
      customized biological, mechanical, and geometrical requirements.

PMID- 16615070
TI  - In vivo performance of a sol-gel glass-coated collagen.
AB  - Synthetic bioactive materials offer possibilities to repair large tissue defects.
      It is well known that bioactivity, angiogenesis, and inflammation are key events
      in implant incorporation. Using glass-coated and glass-free collagen as potential
      bone graft substitutes, we carried out in vitro bioactivity and an in vivo
      angiogenesis and inflammation studies. The in vitro study showed bioactivity when
      the glass-coated samples were left in SBF for 5 days. This was confirmed by FTIR
      results, which presented P--O vibration bands characteristic of hydroxyapatite
      close to 1060 cm(-1) and 600 cm(-1). The in vivo response was evaluated following
      subcutaneous implantation of the biomaterial in the mouse dorsa. Angiogenesis, as
      determined by hemoglobin content extracted from implants 7 and 14 days after
      implantation, increased progressively in both glass-coated and glass-free
      collagen implants. However, vascularization was higher in the glass-coated
      collagen implants 14 days after implantation (mug Hb per mg wet tissue 6.0 +/-
      0.3) compared with the glass-free group (1.6 +/- 0.1). The inflammatory process,
      determined by the levels of myeloperoxidase and N-acetylglucosaminidase, was
      similar for both implants. This study shows that glass-coated collagen implants
      hold osteogenic and angiogenic potential and may be used in clinical conditions
      requiring improvement of these biological processes.

PMID- 16615071
TI  - Microstructures of beta-titanium orthodontic wires joined by infrared brazing.
AB  - The microstructures and interdiffusion in brazed beta-titanium orthodontic wires
      were investigated by scanning electron microscopy and electron probe
      microanalysis, respectively. Beta-titanium wire (Ti-11Mo-6Zr-4Sn) with cross
      section dimensions of 0.032 in. x 0.032 in., titanium-based braze alloy (Ti-30Ni
      20Cu), and silver-based braze alloy (Ag-22Cu-17Zn-5Sn) were selected for the
      study. Brazing was performed using infrared radiation (RS-1) under an argon
      atmosphere. Specimens were etched with two solutions (2.5% HF + 2.5% HNO(3) + 95%
      H(2)O; 25% HN(4)OH + 30% H(2)O(2) + 45%H(2)O). It was found that the silver-based
      braze alloy has a eutectic structure. In the diffusion layer between the beta
      titanium wire and this silver-based braze alloy, Cu and Ti were enriched on the
      wire side, and Sn and Ti were enriched on the braze alloy side. The titanium
      based braze alloy has a dendritic structure. Beta-titanium wire specimens brazed
      with the titanium-based braze alloy had a thicker intermediate area compared to
      the silver alloy; Ti in the diffusion layer had an irregular concentration
      gradient, and the braze alloy side had higher Ti concentration. The original
      microstructure of the beta-titanium wire was not altered with the use of either
      braze alloy. Infrared brazing of beta-titanium orthodontic wire is acceptable for
      clinical use, since the wire microstructure did not deteriorate with either the
      titanium-based or silver-based braze alloy. The differing microstructures of the
      joint regions for the two braze alloys suggest that the joint strengths may also
      differ.

PMID- 16615072
TI  - The effect of crystallinity on strength development of alpha-TCP bone
      substitutes.
AB  - Alpha phase tricalcium phosphates (alpha-TCP) were produced using a solid-state
      reaction method and milled for various periods of time. The resulting four
      materials were alpha-TCPs, ranging in crystalline content. Powders were exposed
      to X-ray diffraction for material identification as well as for use in
      crystallinity and purity calculations. Powder particle size was investigated
      using laser diffraction. Materials were mixed with 2.5% Na(2)HPO(4) solution to
      initiate the hydration of alpha-TCP to calcium-deficient hydroxyapatite (CDHA).
      Isothermal calorimetry was performed to observe thermal response of the powders
      over a period of time. During the reaction process, at various time points up to
      216 h, the material was compression tested to observe strength development.
      Materials proved to be predominantly alpha phase, while amorphous content
      determined by XRD varied. Reactivity, as measured by isothermal calorimetry,
      varied with crystallinity of the alpha-TCP powder. Speed of strength development
      did not change except for the most finely ground powder. In addition, crystal
      size of the CDHA was changed only in the product formed from the most highly
      ground material. It is proposed that increasing reactivity of alpha-TCP cements
      does not result in a corresponding increase in rate of strength development until
      there is sufficient supersaturation to produce significant crystal nucleation.

PMID- 16615073
TI  - Octacalcium phosphate combined with collagen orthotopically enhances bone
      regeneration.
AB  - Octacalcium phosphate (OCP) is resorbable bone regenerative material, but its
      brittleness makes it difficult to maintain its shape without restraint. We have
      engineered a scaffold constructed of synthetic OCP and porcine collagen sponge
      (OCP/Collagen) and investigated whether OCP/Collagen composite could improve bone
      regeneration. To examine this hypothesis, bone regeneration by the implantation
      of OCP/Collagen was compared with those by OCP and collagen. Radiographic and
      histological examination was performed and the percentage of newly formed bone (n
      Bone%) in the defect was determined by a histomorphometrical analysis.
      OCP/Collagen, OCP, or collagen was implanted into the critical-sized defects in
      rat crania and fixed at 2, 4, or 8 weeks after implantation. OCP/Collagen
      improved the handling performance than the granules of OCP, and synergistically
      enhanced the bone regeneration beyond expectation, which were composed of bone
      nucleation by OCP and cell infiltration by collagen. Histomorphometrical analysis
      showed that n-Bone% +/- standard error treated with OCP/Collagen (48.4 +/- 5.14)
      was significantly higher than those with OCP (27.6 +/- 4.04) or collagen (27.4 +/
      5.69) in week 8. The present study suggests that the combination OCP with
      collagen elicited the synergistic effect for bone regeneration.

PMID- 16615074
TI  - Tissue response to in situ polymerization of a new two-solution bone cement:
      evaluation in a sheep model.
AB  - A two-solution bone cement (2-SC) was evaluated in a non-load bearing sheep model
      that simulated insertion of a cemented total joint replacement. A commercial
      powder-liquid bone cement formulation (Palacos R) was used as the control. The
      systemic response to the two cements was determined by monitoring changes in
      arterial blood pressure (ABP) and serum concentrations of methyl methacrylate
      monomer at intervals after insertion of the cement. The short-term tissue
      response to the two cements was assessed by quantifying histomorphometric
      parameters of new bone formation at 2, 4, and 12 weeks postsurgery.
      Intraoperatively, injection and pressurization of bone cement were well
      tolerated, with no significant changes in ABP in either group and no detectable
      circulating monomer in any animal. Several interesting trends were identified in
      the histomorphometry data. In the trabecular specimens, new bone formation
      immediately adjacent to the cement mantle was apparently suppressed in the first
      2 weeks postsurgery, increased dramatically at 4 weeks, and then returned to
      baseline values by 12 weeks. This pattern was seen with both Palacos and 2-SC. In
      the cortical specimens, new bone formation was reduced on the endosteal surface
      when compared with the periosteal surface, with this effect being more noticeable
      at 2 and 4 weeks than at 12 weeks. There were no significant histopathological
      findings in either the bone or the draining lymph nodes. These data indicate that
      the biological response to 2-SC is substantially equivalent to that of Palacos R.
      Additional testing in a functional, load-bearing animal model is now recommended
      to more fully characterize the long-term biological response to 2-SC and to
      determine the mechanical performance of this new cement in vivo.

PMID- 16615075
TI  - Margin failures in brittle dome structures: relevance to failure of dental
      crowns.
AB  - Margin cracks in loaded brittle dome structures are investigated. Dome structures
      consisting of glass shells filled with polymer resin, simulating the essential
      features of brittle crowns on tooth dentin, provide model test specimens. Disk
      indenters of diminishing elastic modulus are used to apply axisymmetric loading
      to the apex of the domes. Previous studies using hard indenters have focused on
      fractures initiating in the near-contact region of such specimens, including
      radial cracks at the glass undersurface directly below the contact axis. Here, we
      focus on fractures initiating at the remote support margins. Margin cracks can
      become dominant when loading forces are distributed over broad contact areas, as
      in biting on soft matter, here simulated by balsa wood disks. Cracks preinitiated
      at the dome edges during the specimen preparation propagate under load around the
      dome side into segmented, semilunar configurations reminiscent of some all
      ceramic crown failures. Finite element analysis is used to determine the basic
      stress states within the dome structures, and to confirm a shift in maximum
      tensile stress from the near-contact area to the dome sides with more compliant
      indenters.

PMID- 16615076
TI  - Intermittent hypoxia impairs performance of adult mice in the two-way shuttle box
      but not in the Morris water maze.
AB  - We have previously found that neonatal intermittent hypobaric hypoxia exposure
      enhanced mouse spatial, but impaired associative, cognition. This study sought to
      investigate the effects of hypobaric hypoxia on adult mice cognition. Mice were
      exposed to 2, 5, 10, 15, or 25 days of intermittent hypoxia (IH; 4 hr/day) at 2
      km (16.0% O2) or 5 km (10.8% O2) altitudes in a hypobaric chamber for the Morris
      water maze (MWM) test and exposed to IH for 2, 10, or 25 days for the shuttle-box
      test. Amino acid dynamics in vivo in the hippocampus and amygdala of mice exposed
      to 2 km hypoxia were analyzed by high-pressure liquid chromatography. The results
      in MWM task showed that IH-2d to -25d at 2 km or 5 km did not change the escape
      latencies of mice in the training test or the retention of platform in the probe
      test. In the shuttle-box task, however, IH-10d at 5 km significantly reduced
      mouse avoidances in the acquisition test on day 4, and IH-10d at 2 km reduced
      avoidances in the retention test; IH-25d at 5 km significantly reduced avoidances
      of mice throughout the acquisition days. Glutamate in the amygdala persisted in
      declining to 69% of baseline at 8 hr posthypoxia (P = 0.040 vs. GLU released
      during 30 min before hypoxia) during the posthypoxia stage. These results suggest
      that adult hypobaric IH impairs the hippocampal-independent, but not the
      hippocampal-dependent, task in mice. The different GLU releases in the
      hippocampus and amygdala in response to hypoxia are involved in the different
      behaviors.

PMID- 16615077
TI  - Crystal structures of thymidylate synthase mutant R166Q: structural basis for the
      nearly complete loss of catalytic activity.
AB  - Thymidylate synthase (TS) catalyzes the folate-dependent methylation of
      deoxyuridine monophosphate (dUMP) to form thymidine monophosphate (dTMP). We have
      investigated the role of invariant arginine 166, one of four arginines that
      contact the dUMP phosphate, using site-directed mutagenesis, X-ray
      crystallography, and TS from Escherichia coli. The R166Q mutant was crystallized
      in the presence of dUMP and a structure determined to 2.9 A resolution, but
      neither the ligand nor the sulfate from the crystallization buffer was found in
      the active site. A second structure determined with crystals prepared in the
      presence of dUMP and the antifolate 10-propargyl-5,8-dideazafolate revealed that
      the inhibitor was bound in an extended, nonproductive conformation, partially
      occupying the nucleotide-binding site. A sulfate ion, rather than dUMP, was found
      in the nucleotide phosphate-binding site. Previous studies have shown that the
      substitution at three of the four arginines of the dUMP phosphate-binding site is
      permissive; however; for Arg166, all the mutations lead to a near-inactive
      mutant. The present structures of TS R166Q reveal that the phosphate-binding site
      is largely intact, but with a substantially reduced affinity for phosphate,
      despite the presence of the three remaining arginines. The position of Cys146,
      which initiates catalysis, is shifted in the mutant and resides in a position
      that interferes with the binding of the dUMP pyrimidine moiety.

PMID- 16615078
TI  - Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering
      glycolytic and gluconeogenic enzymes.
AB  - The role of rutin on carbohydrate metabolism in normal and streptozotocin (STZ)
      induced diabetic rats was investigated in the present study. Administration of
      STZ led to a significant (p <0.05) increase in fasting plasma glucose and a
      decrease in insulin levels. The content of glycogen significantly (p <0.05)
      decreased in liver and muscle, but increased in kidney. The activity of
      hexokinase decreased whereas the activities of glucose-6-phosphatase and fructose
      1,6-bisphosphatase significantly (p <0.05) increased in the tissues. Oral
      administration of rutin (100 mg/kg) to diabetic rats for a period of 45 days
      resulted in significant (p <0.05) alterations in the parameters studied but not
      in normal rats. A decrease of plasma glucose and increase in insulin levels were
      observed along with the restoration of glycogen content and the activities of
      carbohydrate metabolic enzymes in rutin-treated diabetic rats. The
      histopathological study of the pancreas revealed the protective role of rutin.
      There was an expansion of the islets and decreased fatty infiltrate of the islets
      in rutin-treated diabetic rats. In normal rats treated with rutin, we could not
      observe any significant change in all the parameters studied. Combined, these
      results show that rutin plays a positive role in carbohydrate metabolism and
      antioxidant status in diabetic rats.

PMID- 16615079
TI  - A combined HIV-1 protein bead array for serology assay and T-cell subset
      immunophenotyping with a hybrid flow cytometer: a step in the direction of a
      comprehensive multitasking instrument platform for infectious disease diagnosis
      and monitoring.
AB  - BACKGROUND: A new generation of bench-top flow cytometers with digital signal
      processing to perform suspension array technology (SAT) based bead array assays
      as well as leukocyte immunophenotyping is now available. These hybrid instruments
      provide an opportunity for the development of a more cost effective multitasking
      platform to support infectious disease treatment in resource limited countries.
      METHODS: We report the development and testing of two modules compatible with the
      hybrid flow cytometers. The first module is an eleven HIV-1 protein bead array
      (PBA) for the detection of circulating antibodies and the second is a cell based
      T-cell enumeration assay. RESULTS: The HIV-1 PBA was tested in parallel with two
      enzyme immunoassays (EIAs) for the detection of plasma antibodies from 4 HIV-1
      seroconversion panels and a low antibody titer panel. The PBA as well as the two
      EIAs performed equally for the detection of antibody positive samples from all
      seroconversion panels. One antibody positive sample from the low antibody titer
      panel was missed by the PBA together with one of the two EIAs tested. A parallel
      analysis of the HIV-1 PBA with Western blot (a confirmatory test for HIV
      infection) using plasma from nine HIV-1(+) individuals showed that the HIV-1 PBA
      detected more of the gp41 and gp120 antibody positive samples. Preliminary CD4 T
      cell immunophenotyping results from 14 HIV(+) and 10 HIV(-) whole blood specimens
      with the hybrid flow cytometer platform compared well to conventional flow
      cytometry data. CONCLUSION: The successful combination of bead and cell based
      assays on a single hybrid instrument demonstrated the potential utility of a
      multitasking platform. The results presented are providing groundwork for future
      development of more cost effective modular architecture for a flexible flow
      cytometry based platform.

PMID- 16615080
TI  - Epigenetic deregulation of imprinting in congenital diseases of aberrant growth.
AB  - Human chromosome 11p15 comprises two imprinted domains important in the control
      of fetal and postnatal growth. Novel studies establish that imprinting at one of
      these, the IGF2-H19 domain, is epigenetically deregulated (with loss of DNA
      methylation) in Silver-Russell Syndrome (SRS), a congenital disease of growth
      retardation and asymmetry. Previously, the exact opposite epigenetic alteration
      (gain of DNA methylation) had been detected at the domain's 'imprinting control
      region' (ICR) in patients with Beckwith-Wiedemann Syndrome (BWS), a complex
      disorder of fetal overgrowth. However, more frequently, BWS is caused by loss of
      DNA methylation at the ICR that regulates the second imprinted domain at 11p15.
      Interestingly, a similar epigenetic alteration (with loss of methylation) at a
      putative ICR on human chromosome 6q24, is involved in transient neonatal diabetes
      mellitus (TNDM), a congenital disease with intrauterine growth retardation and a
      transient lack of insulin. Thus, fetal and postnatal growth is epigenetically
      controlled by different ICRs, at 11p15 and other chromosomal regions.

PMID- 16615081
TI  - DNA structures at chromosomal translocation sites.
AB  - It has been unclear why certain defined DNA regions are consistently sites of
      chromosomal translocations. Some of these are simply sequences of recognition by
      endogenous recombination enzymes, but most are not. Recent progress indicates
      that some of the most common fragile sites in human neoplasm assume non-B DNA
      structures, namely deviations from the Watson-Crick helix. Because of the single
      strandedness within these non-B structures, they are vulnerable to structure
      specific nucleases. Here we summarize these findings and integrate them with
      other recent data for non-B structures at sites of consistent constitutional
      chromosomal translocations.

PMID- 16615082
TI  - From genes to aggressive behavior: the role of serotonergic system.
AB  - Recent investigations in neurogenomics have opened up new lines of research into
      a crucial genetic problem-the pathway from genes to behavior. This paper
      concentrates on the involvement of protein elements in the brain neurotransmitter
      serotonin (5-HT) system in the genetic control of aggressive behavior.
      Specifically, it describes: (1) the effect of the knockout of MAO A, the
      principal enzyme in 5-HT degradation, (2) the association of intermale aggression
      with the polymorphism in the Tph2 gene encoding the key enzyme in 5-HT synthesis
      in the brain, tryptophan hydroxylase (TPH), and (3) the effect of selective
      breeding for nonaggressive behavior on 5-HT metabolism, TPH activity and 5-HT(1A)
      receptors in the brain. The review provides converging lines of evidence that:
      (1) brain 5-HT contributes to a critical mechanism underlying genetically defined
      individual differences in aggressiveness, and (2) genes encoding pivotal enzymes
      in 5-HT metabolism (TPH and MAO A), 5-HT-transporter, 5-HT(1A) and 5-HT(1B)
      receptors belong to a group of genes that modulate aggressive behavior.

PMID- 16615083
TI  - Functional diversity of FGF-2 isoforms by intracellular sorting.
AB  - Regulation of the subcellular localization of certain proteins is a mechanism for
      the regulation of their biological activities. FGF-2 can be produced as distinct
      isoforms by alternative initiation of translation on a single mRNA and the
      isoforms are differently sorted in cells. High molecular weight FGF-2 isoforms
      are not secreted from the cell, but are transported to the nucleus where they
      regulate cell growth or behavior in an intracrine fashion. 18 kDa FGF-2 can be
      secreted to the extracellular medium where it acts as a conventional growth
      factor by binding to and activation of cell-surface receptors. Furthermore,
      following receptor-mediated endocytosis, the exogenous FGF-2 can be transported
      to the nuclei of target cells, and this is of importance for the transmittance of
      a mitogenic signal. The growth factor is able to interact with several
      intracellular proteins. Here, the mode of action and biological role of
      intracellular FGF-2 are discussed.

PMID- 16615084
TI  - What keeps cells in tissues behaving normally in the face of myriad mutations?
AB  - The use of a reporter gene in transgenic mice indicates that there are many local
      mutations and large genomic rearrangements per somatic cell that accumulate with
      age at different rates per organ and without visible effects. Dissociation of the
      cells for monolayer culture brings out great heterogeneity of size and loss of
      function among cells that presumably reflect genetic and epigenetic differences
      among the cells, but are masked in organized tissue. The regulatory power of a
      mass of contiguous normal cells is expressed in its capacity to normalize the
      appearance and growth behavior of solitary homophilic neoplastic cells, and to
      redirect differentiation of solitary heterophilic stem-like cells. Intimate
      contact between the interacting cells is required to induce these changes. The
      normalization of the neoplastic phenotype does not require gap junctional
      communication between cells, though transdifferentiation might. These varied
      relationships are manifestations of the unifying biological principle of "order
      in the large over heterogeneity in the small".

PMID- 16615085
TI  - A bioinformatician's view of the metabolome.
AB  - The study of a collection of metabolites as a whole (metabolome), as opposed to
      isolated small molecules, is a fast-growing field promising to take us one step
      further towards understanding cell biology, and relating the genetic capabilities
      of an organism to its observed phenotype. The new sciences of metabolomics and
      metabonomics can exploit a variety of existing experimental and computational
      methods, but they also require new technology that can deal with both the amount
      and the diversity of the data relating to the rich world of metabolites. More
      specifically, the collaboration between bioinformaticians and chemoinformaticians
      promises to advance our view of cognate molecules, by shedding light on their
      atomic structure and properties. Modelling of the interactions of metabolites
      with other entities in the cell, and eventually complete modelling of reaction
      pathways will be essential for analysis of the experimental data, and prediction
      of an organism's response to environmental challenges.

PMID- 16615086
TI  - The power of regeneration and the stem-cell kingdom: freshwater planarians
      (Platyhelminthes).
AB  - The great powers of regeneration shown by freshwater planarians, capable of
      regenerating a complete organism from any tiny body fragment, have attracted the
      interest of scientists throughout history. In 1814, Dalyell concluded that
      planarians could "almost be called immortal under the edge of the knife". Equally
      impressive is the developmental plasticity of these platyhelminthes, including
      continuous growth and fission (asexual reproduction) in well-fed organisms, and
      shrinkage (degrowth) during prolonged starvation. The source of their
      morphological plasticity and regenerative capability is a stable population of
      totipotent stem cells--"neoblasts"; this is the only cell type in the adult that
      has mitotic activity and differentiates into all cell types. This cellular
      feature is unique to planarians in the Bilateria clade. Over the last fifteen
      years, molecular studies have begun to reveal the role of developmental genes in
      regeneration, although it would be premature to propose a molecular model for
      planarian regeneration. Genomic and proteomic data are essential in answering
      some of the fundamental questions concerning this remarkable morphological
      plasticity. Such information should also pave the way to understanding the
      genetic pathways associated with metazoan somatic stem-cell regulation and
      pattern formation.

PMID- 16615087
TI  - The evolving role of microRNAs in animal gene expression.
AB  - MicroRNAs (miRNAs) constitute an abundant family of 22-nucleotide RNAs that base
      pair to target mRNAs and typically inhibit their expression. To assess the global
      impact of animal miRNAs on gene regulation, the expression of predicted targets
      and their cognate miRNAs was extensively analyzed in mammals and Drosophila. In
      general, targets are co-expressed at relatively low or undetectable levels in the
      same tissues as the miRNAs predicted to regulate them. Additionally, genes that
      are highly co-expressed with miRNAs usually lack target sites. The authors
      conclude that many animal genes are under evolutionary pressure to maintain or
      avoid complementary sites to miRNAs. Thus, the miRNA pathway broadly contributes
      to the complex gene regulatory networks that shape animal tissue development and
      identity.

PMID- 16615088
TI  - NMDA receptors expressed in oligodendrocytes.
AB  - Oligodendrocytes are known to express (Ca2+)-permeable glutamate receptors and to
      have low resistance to oxidative stress, two factors that make them potentially
      susceptible to injury. Oligodendrocyte injury is intrinsic to the loss of
      function experienced in conditions ranging from cerebral palsy to spinal cord
      injury, focal ischaemia and multiple sclerosis. NMDA receptors, a subtype of
      glutamate receptors, are vital to the remodeling of synaptic connections during
      postnatal development and associative learning abilities in adults and possibly
      in improvements in oligodendrocyte function. Previous studies had failed to
      detect NMDA receptor mRNA or current in oligodendrocytes but three new papers
      demonstrate NMDA receptor expression in oligodendrocytes and discuss its
      implications for ischaemia therapy.

PMID- 16615089
TI  - Structural and functional diversity of adaptor proteins involved in tyrosine
      kinase signalling.
AB  - Adaptors are proteins of multi-modular structure without enzymatic activity.
      Their capacity to organise large, temporary protein complexes by linking proteins
      together in a regulated and selective fashion makes them of outstanding
      importance in the establishment and maintenance of specificity and efficiency in
      all known signal transduction pathways. This review focuses on the structural and
      functional characterisation of adaptors involved in tyrosine kinase (TK)
      signalling. TK-linked adaptors can be distinguished by their domain composition
      and binding specificities. However, such structural classifications have proven
      inadequate as indicators of functional roles. A better way to understand the
      logic of signalling networks might be to look at functional aspects of adaptor
      proteins such as signalling specificity, negative versus positive contribution to
      signal propagation, or their position in the signalling hierarchy. All of these
      functions are dynamic, suggesting that adaptors have important regulatory roles
      rather than acting only as stable linkers in signal transduction.

PMID- 16615090
TI  - Selective forces for the origin of the eukaryotic nucleus.
AB  - The origin of the eukaryotic cell nucleus and the selective forces that drove its
      evolution remain unknown and are a matter of controversy. Autogenous models state
      that both the nucleus and endoplasmic reticulum (ER) derived from the
      invagination of the plasma membrane, but most of them do not advance clear
      selective forces for this process. Alternative models proposing an endosymbiotic
      origin of the nucleus fail to provide a pathway fully compatible with our
      knowledge of cell biology. We propose here an evolutionary scenario that
      reconciles both an ancestral endosymbiotic origin of the eukaryotic nucleus
      (endosymbiosis of a methanogenic archaeon within a fermentative myxobacterium)
      with an autogenous generation of the contemporary nuclear membrane and ER from
      the bacterial membrane. We specifically state two selective forces that operated
      sequentially during its evolution: (1) metabolic compartmentation to avoid
      deleterious co-existence of anabolic (autotrophic synthesis by the methanogen)
      and catabolic (fermentation by the myxobacterium) pathways in the cell, and (2)
      avoidance of aberrant protein synthesis due to intron spreading in the ancient
      archaeal genome following mitochondrial acquisition and loss of methanogenesis.

PMID- 16615091
TI  - Hydra is joining the bandwagon.

PMID- 16615092
TI  - On the utility of scale-free networks.

PMID- 16615093
TI  - Superinduction of metallothionein I by inhibition of protein synthesis: role of a
      labile repressor in MTF-1 mediated gene transcription.
AB  - Induction of metallothioneins (MTs) through the metal-activated transcription
      factor-1 (MTF-1) provides a model response for analyzing transcriptional gene
      regulation by heavy metals. Here, we report inhibition of protein synthesis by
      cycloheximide (CHX) increases induction of Mt1 by approximately five-fold, a
      phenomenon designated as "superinduction." Characterization of superinduction
      revealed it is time- and concentration-dependent of CHX, requires the presence of
      an MTF-1 activator, and occurs at a transcriptional level, suggesting a labile
      repressor in the control of Mt1 induction. Genetic analyses using Mtf1 null cells
      and a metal response element (MRE)-driven reporter construct showed that
      superinduction of Mt1 is mediated through MTF-1 and MRE-dependent transcription.
      Analyses of intracellular zinc content by inductively coupled plasma emission
      spectroscopy and fluorescence imaging demonstrated that treatment with CHX alone
      or CHX plus an inducer does not increase the total zinc accumulation or the
      concentration of free zinc in cells under the conditions in which superinduction
      occurs. Moreover, superinduction was observed in cells cultured in a zinc
      depleted medium, suggesting that superinduction does not involve elevation of
      intracellular zinc concentration. Northern blotting showed that Cd, CHX, or Cd +
      CHX does not affect the expression of the mRNA of MTF-1. Immunoblotting using
      antibodies specific for MTF-1 demonstrated that Cd induces a down-regulation of
      the MTF-1 protein, whereas cotreatment with Cd and CHX blocked the Cd-induced
      degradation of MTF-1. The findings reveal a new mechanistic aspect of the
      superinduction of Mt1, in which a labile repressor negatively controls agonist
      induced turnover of the MTF-1 protein.

PMID- 16615094
TI  - Temporal kinetics and concentration-response relationships for induction of
      CYP1A, CYP2B, and CYP3A in primary cultures of beagle dog hepatocytes.
AB  - Compared to other species, little information is available on the xenobiotic
      induced regulation of cytochrome P450 enzymes in the beagle dog. Dogs are widely
      used in the pharmaceutical industry for many study types, including those that
      will impact decisions on compound progression. The purpose of this study was (1)
      to determine the temporal kinetics of drug-induced changes in canine CYP1A,
      CYP2B, and CYP3A mRNA and enzymatic activity, and (2) to characterize
      concentration-response relationships for CYP1A2, CYP2B11, and CYP3A12 using
      primary cultures of canine hepatocytes treated with beta-naphthoflavone (BNF),
      phenobarbital (PB), and rifampin (RIF), respectively. CYP1A1 and CYP1A2 mRNA
      exhibited maximal expression (12,700-fold and 206-fold, respectively) after 36 h
      of treatment with BNF. PB treatment, but not RIF treatment, caused maximal
      induction of CYP2B11 mRNA (149-fold) after 48 h of treatment. CYP3A12 and CYP3A26
      mRNA levels were increased maximally after 72 h of treatment with PB and RIF
      (CYP3A12, 35-fold and 18-fold, and CYP3A26, 72-fold and 22-fold with PB and RIF
      treatment, respectively). Concentration-response relationships for BNF induced 7
      ethoxyresorufin O-dealkylation (EROD) (EC(50) = 7.8 +/- 4.2 microM), PB induced 7
      benzyloxyresorufin O-dealkylation (BROD) (EC(50) = 123 +/- 30 microM), and PB and
      RIF induced testosterone 6beta-hydroxylation (EC(50) = 132 +/- 28 microM and 0.98
      +/- 0.16 microM) resembled the relationship for human CYP induction compared to
      that of rodent. Interestingly, RIF had no effect on CYP2B11 expression, which
      represents a species difference overlooked in previous investigations. Overall,
      the induction of dog CYP1A, CYP2B, and CYP3A exhibits characteristics that are
      intermediate to those of rodent and human.

PMID- 16615095
TI  - TCDD suppresses insulin-responsive glucose transporter (GLUT-4) gene expression
      through C/EBP nuclear transcription factors in 3T3-L1 adipocytes.
AB  - TCDD is known to reduce significantly the level of the functionally active form
      of glucose transporter type 4 (GLUT4) in vivo in adipose tissue and muscles. To
      study the mechanistic basis of this phenomenon, we conducted transient
      transfection and DNA deletion analysis in 3T3-L1 cells using chloramphenicol
      acetyltransferase (CAT) reporter plasmids containing the GLUT4 promoter joined to
      the bacterial CAT. It was found that in transfected control samples, CAT activity
      was significantly higher in cells transfected with p469CAT and p273CAT than those
      with p78CAT, indicating that the region between -78 and -273 contained elements
      that play major roles in transactivation of this gene. Treatment with TCDD
      decreased CAT activity with p469CAT and p273CAT, but not with p78CAT, indicating
      the same region to contain the element(s) affected by TCDD. A gel-shift (EMSA)
      analysis result indicated that TCDD shows the profound effect only on the nuclear
      proteins binding to the [(32)P]-labeled probe containing C/EBP response element
      equivalent of the -265 to -242 stretch of the GLUT4 promoter. The results of
      supershift analysis showed that TCDD caused a decrease in the tier of C/EBPalpha
      and an increase in that of C/EBPbeta among the proteins bound to this C/EBP
      response element. We studied the effect of TCDD in cells overexpressing either
      C/EBPalpha, C/EBPbeta, or C/EBPdelta through transient transfection of p273CAT or
      p469CAT. The results clearly showed that the effect of TCDD to suppress the CAT
      activity of p273 or p469 disappeared in those cells overexpressing C/EBPalpha or
      C/EBPbeta. These results implicate the C/EBP proteins to be the main mediator of
      suppressive action of TCDD on GLUT4 gene expression in 3T3-L1 cells.

PMID- 16615096
TI  - Biologic and immunomodulatory events after CTLA-4 blockade with ticilimumab in
      patients with advanced malignant melanoma.
AB  - BACKGROUND: T-regulatory (TR) cells expressing cytotoxic T lymphocyte-associated
      antigen-4 (CTLA-4) maintain peripheral immune tolerance and negatively affect
      host immune responses against cancer. The immunobiologic effects of ticilimumab,
      a human monoclonal antibody against CTLA-4, was administered to patients with
      metastatic melanoma who participated in a Phase I/II clinical trial. METHODS:
      Thirty patients who received ticilimumab at a dose of 10 mg/kg monthly (n=20) or
      15 mg/kg every 3 months (n=10) were studied at study entry and at 14-day
      intervals thereafter to assess lymphocyte immunophenotypes, interleukin (IL)-2
      and IL-10 production, and the expression of TR-related genes in peripheral blood
      mononuclear cells (PBMC) from a subset of patients was studied by real-time
      polymerase chain reaction. RESULTS: Four of 12 patients with immune-related
      adverse events (IRAE) attained objective antitumor responses (ATR), whereas only
      1 of 18 patients without IRAE attained ATR (chi2=4.0; P=.0455). Patients with ATR
      had significant reductions in T(R) cells and constitutive IL-10 production
      accompanied by a significant increase in IL-2 production by activated T cells.
      Although IRAE+/ATR+ patients demonstrated a positive correlation between CTLA-4
      and glucocorticoid-induced tumor necrosis factor receptor (GITR) transcripts
      (Spearman rho=.522; P=.015), IRAE-/ATR- patients had a positive correlation
      between the transcripts of CTLA-4 and program death-1 (PD-1) receptor (Spearman
      rho=.891; P=.000). CONCLUSIONS: Antitumor responses in patients with metastatic
      melanoma who were treated with ticilimumab were found to be correlated with
      reductions in TR cells and constitutive secretion of IL-10, an increase in IL-2
      production, and a positive correlation between transcripts of CTLA-4 and GITR.
      Conversely, a lack of ATR was found to be correlated with steady levels of TR
      cells and constitutive IL-10 secretion, and a positive correlation between the
      transcripts of CTLA-4 and PD-1.

PMID- 16615097
TI  - Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate
      cancer.
AB  - BACKGROUND: Doxorubicin plus ketoconazole has exhibited significant activity in
      patients with advanced prostate cancer. However, overall and cardiac-specific
      toxicity was reported to be high. Mitoxantrone has activity similar to that of
      doxorubicin, is less cardiotoxic, and is widely used to treat prostate cancer.
      The current study sought to evaluate the toxicity and activity of mitoxantrone
      plus ketoconazole in a cohort of patients with hormone-refractory prostate
      cancer. METHODS: Progression after medical or surgical castration and, for those
      patients receiving antiandrogens, progression after withdrawal was required, as
      was objective evidence of metastasis, castrate levels of testosterone, an Eastern
      Cooperative Oncology Group (ECOG) performance status of 0 to 2, and intact
      cardiac function. After enrollment onto a multicenter local consortium study,
      subjects were treated with mitoxantrone at a dose of 12 mg/m2 intravenously every
      3 weeks plus continuous oral ketoconazole at a dose of 400 mg 3 times daily and
      ascorbic acid at a dose of 250 mg. Replacement doses of hydrocortisone were
      given. RESULTS: For 40 enrolled subjects, the median prostate-specific antigen
      and ECOG performance status were 68 and 1, respectively, 53% had Gleason scores
      of 8 to 10, and all had metastasis. Predominant Grade 3/4 toxicities were:
      neutropenia in 13%, neutropenic fever in 10%, and anemia in 13%. Of 37 evaluable
      patients, 8% achieved a complete remission (CR) and 62% achieved a partial
      remission (PR), for a CR plus PR rate of 70%. For soft tissue and bone disease,
      overall response rates were 13% and 8%, respectively. The median progression-free
      survival and overall survival were 10 months and 18 months, respectively.
      CONCLUSIONS: Mitoxantrone plus ketoconazole is well tolerated, is active in
      hormone-refractory prostate cancer, and should be studied further.

PMID- 16615098
TI  - Prostate cancer cells use genetic and epigenetic mechanisms for progression to
      androgen independence.
AB  - Studies on the genetic basis of prostate cancer (PCa) have lead to mixed results
      with the only consensus being that PCa is a complex disease. Our goal was to gain
      insight into potential events involved in the acquisition of the androgen
      refractory phenotype in PCa cells regardless of DNA-change dependence. To this
      end, we examined two LNCaP PCa cell line models of progression-one developed in
      vivo and one developed in vitro-using molecular cytogenetic and microarray gene
      expression analyses and extended this investigation of specific events into PCa
      tumors. The chromosomal changes observed in both in vivo and in vitro androgen
      independent cell lines are similar to those seen in PCa during tumor progression.
      Correspondingly, gene expression analysis showed significant heterogeneity in the
      genes expressed among androgen-independent cells, but with some common gene
      expression changes that correlated with the acquired androgen-independent
      phenotype. Thus, growth conditions under which the cells progress appeared to
      impact the mechanisms used for progression, albeit within tumor-type-specific
      pathways. Our findings suggest that a dynamic and adaptable combination of
      epigenetic and DNA-change-dependent events can be used by PCa cells for the
      acquisition of the androgen-independent phenotype. This article contains
      Supplementary Material available at http://www.interscience.wiley.com/jpages/1045
      2257/suppmat.

PMID- 16615099
TI  - Tilapia (Oreochromis niloticus) vitellogenins: development of homologous and
      heterologous ELISAs and analysis of vitellogenin pathway through the ovarian
      follicle.
AB  - Vitellogenin (VTG) of Oreochromis niloticus was again purified, due to the
      conflicting results found in the literature. Three purification processes have
      been used: electrophoresis and electro-elution, double chromatography (gel
      filtration and ion-exchange chromatography) and single ion-exchange
      chromatography. Using SDS-PAGE we confirmed in all cases the presence of two
      polypeptidic forms of plasma VTG of 130 kDa (VTG1) and 170 kDa (VTG2). We raised
      polyclonal antibodies against each VTG form and we demonstrated the complete
      cross-reactivity of each antibody with both forms of VTG by Enzyme Immuno-Assay
      (EIA) and Western blots. The homologous ELISAs developed exhibited a detection
      limit of 6 ng x ml(-1), equivalent to 60 ng x ml(-1) of plasma VTG and allowed us
      to quantify the total plasma VTG of O. niloticus with high specificity and
      sensitivity. Using photonic and electron immunomicroscopy, we followed the
      pathway of VTG into the ovarian follicle (OF) demonstrating that VTG enters the
      oocyte at stage 3 of OF development, at the same time as cortical alveoli and
      lipid globules appear. Heterologous ELISAs performed on other cichlid species
      allowed us to quantify plasma VTG in Oreochromis aureus and Sarotherodon
      melanotheron and to detect it in Hemichromis fasciatus, Hemichromis bimaculatus
      and Tilapia zillii, constituting a reliable tool for monitoring the presence of
      xeno-estrogens in the environment of these fish species.

PMID- 16615100
TI  - Membrane trafficking factors are involved in the hypotonic activation of the
      taurine channel in the little skate (Raja erinacea) red blood cell.
AB  - In response to volume expansion, red blood cells of the little skate (Raja
      erinacea) initially swell and then release small organic compounds and
      osmotically obligated water in what is called a regulatory volume decrease (RVD)
      to restore cell volume. One of the major intracellular solutes lost during this
      process is the non-metabolized beta amino acid taurine. This hypoosmotic-induced
      increase in cell taurine permeability requires the anion exchanger, skAE1. The
      abundance of this transporter increases on the surface plasma membrane by a
      process of exocytosis. The second-messenger pathways involved in exocytosis of
      skAE1 were investigated with the use of inhibitors which affect membrane
      trafficking. Hypoosmotic-stimulated taurine uptake was significantly decreased by
      42% with wortmannin, a phosphatidylinositol 3-kinase (PI3 kinase) inhibitor.
      Additional evidence for the involvement of PI3K was obtained with a second
      inhibitor, LY294002, which decreased the hypoosmotic-stimulated taurine uptake by
      28%. The state of actin is also involved, as the actin filament depolymerizer
      latrunculin B decreased hypoosmotic-stimulated taurine uptake by approximately
      40%. Although hypoosmotic conditions did not stimulate changes in the
      distribution of actin between filamentous and globular forms, latrunculin
      stimulated a decrease in filamentous actin and increase in globular actin in both
      isoosmotic and hypoosmotic conditions. Disruptors of other potential cytoskeletal
      factors (myosin, kinesin, dynein, and microtubules) did not affect taurine
      uptake. The present results suggest that the exocytosis of skAE1 stimulated by
      hyposmotic-induced cell volume expansion requires activation of PI3 kinase and is
      regulated by the state of actin filaments.

PMID- 16615101
TI  - Modulation and variability of prey capture kinematics in clariid catfishes.
AB  - Species with narrow or limited diets (trophic specialists) are expected to be
      less flexible in their feeding repertoire compared to species feeding on a wide
      range of different prey (trophic generalists). The ability to modulate prey
      capture kinematics in response to different prey types and prey position, as well
      as the overall variability in prey capture kinematics, is evaluated in four
      clariid species ranging from trophic generalist (Clarias gariepinus) to species
      with morphological specializations and a narrow diet (Channallabes apus and
      Gymnallabes typus). High-speed video recordings were made of prey captures on two
      prey that differ in shape, attachment strength and hardness. While the observed
      amount of strike-to-strike variability in prey capture kinematics is similar for
      all species and not influenced by prey type, only the two less specialized
      species showed the ability to modulate their prey capture kinematics in function
      of the presented prey types. All species did, however, show positional modulation
      during the strike by adjusting the magnitude of neurocranial elevation. These
      results indicate that the narrow dietary breadth of trophic specialists is indeed
      indicative of functional stereotypy in this group of fishes. Although most
      studies focussing on prey processing found a similar result, the present study is
      one of the few that was able to demonstrate this relationship when focussing on
      prey capture mechanics. Possibly, this relationship is less frequently observed
      for prey capture compared to prey processing because, regardless of prey type,
      the initial capture of prey requires a higher amount of variability.

PMID- 16615102
TI  - Sensitivity and specificity of confocal laser-scanning microscopy for in vivo
      diagnosis of malignant skin tumors.
AB  - BACKGROUND: Melanoma and nonmelanoma skin cancer are the most frequent malignant
      tumors by far among whites. Currently, early diagnosis is the most efficient
      method for preventing a fatal outcome. In vivo confocal laser-scanning microscopy
      (CLSM) is a recently developed potential diagnostic tool. METHODS: One hundred
      seventeen melanocytic skin lesions and 45 nonmelanocytic skin lesions (90 benign
      nevi, 27 malignant melanomas, 15 basal cell carcinomas, and 30 seborrheic
      keratoses) were sampled consecutively and were examined using proprietary CLSM
      equipment. Stored images were rated by 4 independent observers. RESULTS:
      Differentiation between melanoma and all other lesions based solely on CLSM
      examination was achieved with a positive predictive value of 94.22%. Malignant
      lesions (melanoma and basal cell carcinoma) as a group were diagnosed with a
      positive predictive value of 96.34%. Assessment of distinct CLSM features showed
      a strong interobserver correlation (kappa >0.80 for 11 of 13 criteria).
      Classification and regression tree analysis yielded a 3-step algorithm based on
      only 3 criteria, facilitating a correct classification in 96.30% of melanomas,
      98.89% of benign nevi, and 100% of basal cell carcinomas and seborrheic
      keratoses. CONCLUSIONS: In vivo CLSM examination appeared to be a promising
      method for the noninvasive assessment of melanoma and nonmelanoma skin tumors.

PMID- 16615103
TI  - How do genes make teeth to order through development?
AB  - This introduction to new patterning theories for the vertebrate dentition
      outlines the historical concepts to explain graded sequences in tooth shape in
      mammals (incisors, canines, premolars, molars) which change in evolution in a
      linked manner, constant for each region. The classic developmental models for
      shape regulation, known as the 'regional field' and 'dental clone' models, were
      inspired by the human dentition, where it is known that the last tooth in each
      series is the one commonly absent. The mouse, as a valuable experimental model,
      has provided data to test these models and more recently, based on spatial
      temporal gene expression data, the 'dental homeobox code' was proposed to specify
      regions and regulate tooth shape. We have attempted to combine these hypotheses
      in a new model of the combinatorial homeobox gene expression pattern with the
      clone and field theories in one of 'co-operative genetic interaction'. This also
      explains the genetic absence of teeth in humans ascribed to point mutations in
      mesenchymally expressed genes, which affect tooth number in each series.

PMID- 16615104
TI  - Immunological characterization and fine localization of a lizard beta-keratin.
AB  - Scales of lizards contain beta-keratin of poorly known composition. In the
      present study, a rat polyclonal serum against a lizard beta-keratin of 14-15 kDa
      has been produced and the relative protein has been immunolocalized in the
      epidermis. The observations for the first time show that the isolated protein
      band derives from the extraction of a protein component of the beta-keratin
      filaments of lizard epidermis. In immunoblots and immunocytochemistry, the
      antiserum recognizes most lizard beta-keratins, but produces a variable cross
      reactivity with snake beta-keratins, and weak or no reactivity with beta-keratins
      isolated from tuatara, turtles, alligator and birds. In bidimensional immunoblots
      of lizard epidermis, three main spots at 15-16 kDa with isoelectric point at 7.0,
      7.6 and 8.0, and an unresolved large spot at 29-30 kDa and with pI at 7.5-8.0,
      are obtained, may be derived from the aggregation of smaller beta-keratin
      proteins. The ultrastructural immunolocalization with the antibody against lizard
      beta-keratin shows that only small and large beta-keratin filaments of beta-cells
      of lizard epidermis are labeled. Keratin bundles in oberhautchen cells are less
      immunolabeled. Beta-keratin is rapidly polymerized into beta-packets that merge
      into larger beta-keratin filaments. No labeling is present over other cell
      organelles or cell layers of lizard epidermis, and is absent in non-epidermal
      cells. The antiserum recognizes epitope(s) characteristics for lizard beta
      keratins, partially recognized in snakes and absent in non-lepidosaurian species.
      This result indicates that beta-keratins among different reptilian groups posses
      different immunoreactive regions.

PMID- 16615105
TI  - The serial transformation hypothesis of vertebrate origins: comment on "The new
      head hypothesis revisited".
AB  - In "The New Head Hypothesis Revisited," R.G. Northcutt (2005. J Exp Zool (Mol Dev
      Evol) 304B:274-297) evaluates the original postulates of this hypothesis
      (Northcutt and Gans, 1983. Quart Rev Biol 58:1-28). One of these postulates is
      that the brain-particularly the forebrain-evolved at essentially the same time as
      many neural crest and neurogenic placode derivatives-including sensory ganglia,
      dermal skeleton and sensory capsules of the head, and branchial arches.
      Northcutt's subsequent paper in 1996 concluded with the idea that transitional
      forms might not have occurred at the origin of vertebrates. Butler proposed a
      "Serial Transformation" hypothesis in 2000, which disputed the latter idea in
      that paired eyes and an enlarged brain (but lacking telencephalon) were
      envisioned to have been gained before elaboration of most neural crest and
      neurogenic placodal derivatives. In 2003, J. Mallatt and J.-Y. Chen analyzed
      fossils of the Cambrian animal Haikouella, which strongly support its affinity to
      craniates and aspects of several hypotheses, including Butler's transformational
      model, because although branchial bars are present, most other neural crest and
      placodal derivatives are absent, while paired eyes and an enlarged brain (but
      probably without telencephalon) are present. A more complete picture of
      vertebrate origins can be realized when the various hypotheses are constructively
      reconciled.

PMID- 16615106
TI  - Expression of a Gsx parahox gene, Cnox-2, in colony ontogeny in Hydractinia
      (Cnidaria: Hydrozoa).
AB  - The ontogeny of colonial animals is markedly distinct from that of solitary
      animals, yet no regulatory genes have thus far been implicated in colonial
      development. In cnidarians, colony ontogeny is characterized by the production of
      a nexus of vascular stolons, from which the feeding and reproductive structures,
      called polyps, are budded. Here we describe and characterize the Gsx parahox
      gene, Cnox-2, in the colonial cnidarian Hydractinia symbiolongicarpus of the
      class Hydrozoa. Cnox-2 is expressed in prominent components of the colony-wide
      patterning system; in the epithelia of distal stolon tips and polyp bud
      rudiments. Both are regions of active morphogenetic activity, characterized by
      cytologically and behaviorally distinct epithelia. Experimental induction and
      elimination of stolonal tips result in up- and down-regulation, respectively, of
      Cnox-2 expression. In the developing polyp, Cnox-2 expression remains uniformly
      high throughout the period of axial differentiation. The differential oral-aboral
      Cnox-2 expression in the epithelia of the mature polyp, previously described for
      this and another hydrozoan, arises after oral structures have completed
      development. Differential Cnox-2 expression is, thus, associated with key aspects
      of patterning of both the colony and the polyp, a finding that is particularly
      striking given that polyp and colony form are dissociable in the evolution of
      Hydrozoa.

PMID- 16615107
TI  - Low prevalence of (pre) malignant lesions in the breast and high prevalence in
      the ovary and Fallopian tube in women at hereditary high risk of breast and
      ovarian cancer.
AB  - To analyse the prevalence of (pre) malignant lesions occurring in breast and
      adnexal tissue at prophylactic surgery in women at hereditary high risk of breast
      and/or ovarian cancers. Tissue was obtained from 85 women who underwent
      prophylactic bilateral salpingo-oophorectomy (pBSO) and from 59 women who
      underwent prophylactic mastectomy (pM). Control tissue samples were obtained from
      women undergoing breast reduction surgery (N = 99) or adnexal surgery for benign
      reasons (N = 72). In women with a BRCA1/2 mutation, the prevalence of a (pre)
      malignant adnexal lesion was 50% (95% CI 26-74) if older than 40 years and 14%
      (95% CI 0-58) if younger. The prevalences of (pre) malignant breast lesions in
      women older than 40 years, with and without a BRCA1/2 mutation, were 0% (95% CI 0
      16) and 47% (95% CI 21-73), respectively. No association was found between (pre)
      malignant lesions in breast and adnexal tissue occurring in 28 women who
      underwent surgery on both organs (R = 0.155, p = 0.432), but the prevalence of
      lesions was significantly higher in adnexal tissue than in the breast (p =
      0.023). Compared to controls, women at hereditary high risk had a higher chance
      of (pre) malignant lesions in the breast and an even higher chance of such
      lesions in the adnexal tissue. There was no indication for concomitant presence
      of such lesions in both organs at the time of prophylactic surgery. The high
      frequency of (pre) malignant lesions in the adnexal tissue stresses further the
      importance of pBSO from the age of 40 onwards in women at hereditary high risk.

PMID- 16615108
TI  - Alcohol consumption and prostate cancer risk: results from the Melbourne
      collaborative cohort study.
AB  - Although there is little evidence to support an association between alcohol
      consumption and prostate cancer risk, questions remain concerning the effect on
      aggressive and nonaggressive tumours and the pattern and type of alcohol
      consumed. In a prospective cohort of 16,872 men aged 27-70 years at recruitment
      and followed-up from 1994 to the end of 2003, 732 incident prostate cancers were
      identified through the local population cancer registry, including 132 aggressive
      cases and 53 prostate cancer deaths. Detailed information on alcohol consumption
      was taken at baseline by trained interviewers using a structured questionnaire.
      Overall, alcohol intake was not associated with prostate cancer incidence.
      Compared to abstainers, men consuming 1-19 g/d of alcohol had a slightly reduced
      incidence of aggressive prostate cancers (hazard ratio 0.67; 95% confidence
      interval (CI) 0.43, 1.06) and prostate cancer mortality (hazard ratio 0.56; 95%
      CI 0.28, 1.14), but their risk of nonaggressive prostate cancers was close to
      unity (hazard ratio 1.09; 95% CI 0.85, 1.40). No significant association with
      pattern of drinking or type of alcoholic beverage was found. Our results show
      that alcohol consumption does not influence overall prostate cancer incidence but
      we found suggestive evidence that alcohol consumption might decrease the
      incidence of aggressive prostate cancer and mortality.

PMID- 16615109
TI  - Circulating MMP2 and MMP9 in breast cancer -- potential role in classification of
      patients into low risk, high risk, benign disease and breast cancer categories.
AB  - Matrix metalloproteinase (MMP) 2 and 9 are involved in cancer invasion and
      metastasis, and increased levels occur in serum and plasma of breast cancer (BC)
      patients. It is, however, unclear whether changes in serum levels can be
      exploited for early detection or classification of patients into different
      risk/disease categories. In our study, we measured concentration and activity of
      MMP2/9 in sera of 345 donors classified as low risk (Gail score <1.7), high risk
      (HR) (Gail score > or =1.7), benign disease or BC. Kruskal-Wallis and Mann
      Whitney nonparametric tests showed that total-MMP2 concentration is higher in HR
      compared to control (p = 0.012), benign (p = 0.001) and cancer (p = 0.007).
      Active MMP2 (aMMP2) concentration is higher in control than benign and cancer (p
      < 0.001, respectively). Total and aMMP9 concentrations are higher in cancer than
      benign (p < 0.001, p = 0.002, respectively). Total-MMP2 and total-MMP9 activities
      are lower in control than benign (p < 0.001, p = 0.002, respectively) and cancer
      (p < 0.001, respectively). Total-MMP2 and MMP9 activities are also higher in
      cancer than benign (p = 0.004, p < 0.001) and HR (p = 0.008, p = 0.007,
      respectively). These results were not affected by age or inclusion/exclusion of
      donors with noninvasive cancer or atypical hyperplasia. Linear discriminant
      analysis revealed that HR donors are characterized by lower total-MMP2 and higher
      aMMP2. Overall group classification accuracy was 64.5%. Independent validation
      based on the leave-one-out cross validation approach gave an overall
      classification of 63%. Our study provides evidence supporting the potential role
      of serum MMP2/9 as biomarkers for breast disease classification.

PMID- 16615110
TI  - No association between HPV infection and the neoplastic progression of esophageal
      squamous cell carcinoma: result from a cross-sectional study in a high-risk
      region of China.
AB  - Esophageal cancer is a leading cause of cancer death, especially in developing
      countries. In high-risk regions, squamous cell carcinoma is the most common type
      of esophageal cancer, and its etiology remains poorly understood. The purpose of
      this study was to evaluate the association between human papillomavirus (HPV)
      infection and esophageal squamous cell carcinoma (ESCC) and related precursor
      lesions in a high-risk area of China. We conducted a cross-sectional study among
      adult inhabitants of Linxian, China. All subjects were interviewed about
      potential risk factors, had the length of their esophagus sampled by a balloon
      cytology examination and underwent endoscopy with mucosal iodine staining and
      biopsy of all unstained lesions. A multivalent HPV hybridization probe, Digene
      Hybrid Capture II (Gaithersburg, MD), which recognizes high-risk types 16, 18,
      31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, was used to determine the HPV
      infection status of the cytologic specimens, and the endoscopic biopsies were
      used to classify each subject's esophageal disease. 740 subjects completed the
      cytologic and endoscopic exams, and 702 had adequate cytologic and biopsy
      specimens. Using a cutpoint of > or =3.0 pg/ml of HPV DNA to define a positive
      test, HPV positivity was identified in 13% (61/475) of subjects without squamous
      dysplasia, 8% (8/102) with mild dysplasia, 7% (6/83) with moderate dysplasia, 16%
      (6/38) with severe dysplasia and zero (0/4) with invasive ESCC. Changing the
      cutpoint defining a positive test did not change the association of HPV infection
      and dysplasia grade. In this high-risk population, infection of esophageal cells
      with high-risk HPV types occurs in 13% of asymptomatic adults with no evidence of
      squamous dysplasia and a similar proportion of individuals with mild, moderate or
      severe dysplasia. This suggests that HPV infection is not a major risk factor for
      ESCC in this high-risk Chinese population. Further studies are warranted to
      determine if infection with this agent is associated with neoplastic progression
      in a subset of cases.

PMID- 16615111
TI  - Characterization of copper binding to the peptide amyloid-beta(1-16) associated
      with Alzheimer's disease.
AB  - Amyloid-beta peptide (Abeta) is the principal constituent of plaques associated
      with Alzheimer's disease (AD) and is thought to be responsible for the
      neurotoxicity associated with the disease. Copper binding to Abeta has been
      hypothesized to play an important role in the neruotoxicity of Abeta and free
      radical damage, and Cu2+ chelators represent a possible therapy for AD. However,
      many properties of copper binding to Abeta have not been elucidated clearly, and
      the location of copper binding sites on Abeta is also in controversy. Here we
      have used a range of spectroscopic techniques to characterize the coordination of
      Cu2+ to Abeta(1-16) in solution. Electrospray ionization mass spectrometry shows
      that copper binds to Abeta(1-16) at pH 6.0 and 7.0. The mode of copper binding is
      highly pH dependent. Circular dichroism results indicate that copper chelation
      causes a structural transition of Abeta(1-16). UV-visible absorption spectra
      suggest that three nitrogen donor ligands and one oxygen donor ligand (3N1O) in
      Abeta(1-16) may form a type II square-planar coordination geometry with Cu2+. By
      means of fluorescence spectroscopy, competition studies with glycine and L
      histidine show that copper binds to Abeta(1-16) with an affinity of Ka
      approximately 10(7) M(-1) at pH 7.8. Besides His6, His13, and His14, Tyr10 is
      also involved in the coordination of Abeta(1-16) with Cu2+, which is supported by
      1H NMR and UV-visible absorption spectra. Evidence for the link between Cu2+ and
      AD is growing, and this work has made a significant contribution to understanding
      the mode of copper binding to Abeta(1-16) in solution.

PMID- 16615112
TI  - Differences between first and subsequent rounds of the MRISC breast cancer
      screening program for women with a familial or genetic predisposition.
AB  - BACKGROUND: Within the Dutch MRI Screening (MRISC) study, a Dutch multicenter
      screening study for hereditary breast cancer, the authors investigated whether
      previously reported increased diagnostic accuracy of magnetic resonance imaging
      (MRI) compared with mammography would be maintained during subsequent screening
      rounds. METHODS: From November 1999 to October 2003, 1909 eligible women were
      included in the study. Screening parameters and tumor characteristics of
      different rounds were calculated and compared. The authors defined 3 different
      types of imaging screening rounds: first round in women never screened by imaging
      before, first round in women screened by imaging (mainly mammography) before, and
      subsequent rounds. RESULTS: The difference in sensitivity for invasive cancers
      between mammography and MRI was largest in the first round of women previously
      screened with mammography (20.0 vs. 93.3%; P=.003), but also in subsequent
      rounds, there was a significant difference in favor of MRI (29.4 vs. 76.5%;
      P=.02). The difference in false-positive rate between mammography and MRI was
      also largest in the first round of women previously screened with mammography
      (5.5 vs. 14.0%; P<.001), and it remained significant in subsequent rounds (4.6
      vs. 8.2%; P<.001). Screen-detected tumors were smaller and more often lymph node
      negative than symptomatic tumors in age-matched control patients, but no major
      differences in tumor stage were found between tumors detected at subsequent
      rounds compared with those in the first round. CONCLUSIONS: In subsequent rounds,
      a significantly higher sensitivity and better discriminating capacity of MRI
      compared with mammography was maintained, and a favorable tumor stage compared
      with age-matched symptomatic controls. As results of these subsequent screening
      rounds were most predictive for long-term effects, the authors expect that this
      screening program will contribute to a decrease of breast cancer mortality in
      these high-risk women.

PMID- 16615113
TI  - EphB4 provides survival advantage to squamous cell carcinoma of the head and
      neck.
AB  - The receptor tyrosine kinase EphB4 and its ligand EphrinB2 play critical roles in
      blood vessel maturation, and are frequently overexpressed in a wide variety of
      cancers. We studied the aberrant expression and biological role of EphB4 in head
      and neck squamous cell carcinoma (HNSCC). We tested the effect of EphB4-specific
      siRNA and antisense oligonucleotides (AS-ODN) on cell growth, migration and
      invasion, and the effect of EphB4 AS-ODN on tumor growth in vivo. All HNSCC tumor
      samples express EphB4 and levels of expression correlate directly with higher
      stage and lymph node metastasis. Six of 7 (86%) HNSCC cell lines express EphB4,
      which is induced either by EGFR activation or by EPHB4 gene amplification.
      EphrinB2 was expressed in 65% tumors and 5 of 7 (71%) cell lines. EphB4 provides
      survival advantage to tumor cells in that EphB4 siRNA and AS-ODN significantly
      inhibit tumor cell viability, induce apoptosis, activate caspase-8, and sensitize
      cells to TRAIL-induced cell death. Furthermore, EphB4-specific AS-ODN
      significantly inhibits the growth of HNSCC tumor xenografts in vivo. Expression
      of EphB4 in HNSCC tumor cells confers survival and invasive properties, and
      thereby provides a strong rationale for targeting EphB4 as novel therapy for
      HNSCC.

PMID- 16615114
TI  - Intratumoural expression of TNF-R1 and EMAP-II in relation to response of
      patients treated with TNF-based isolated limb perfusion.
AB  - Tumour necrosis factor-alpha (TNF) has been used in the clinic for more than 10
      years in an isolated limb perfusion (ILP). However, intra-tumoural expression of
      TNF receptor-1 (TNF-R1) and TNF-R1 upregulating factors are unknown. We
      determined the expression of TNF-R1, proEMAP and endothelial monocyte-activating
      polypeptide-II (EMAP-II) before and after ILP and evaluated this against clinical
      response. Tumour biopsies were taken before and after ILP of patients (n = 27)
      with advanced sarcoma or metastatic melanoma. Biopsies were randomly analysed by
      western blotting for proEMAP/EMAP-II and TNF-R1 expression. Appropriate melanoma
      biopsies were stained for EMAP-II, TNF-R1, CD31 and CD68. For melanomas we found
      that an up-regulation of EMAP-II, in contrast to proEMAP or TNF-R1, directly
      after ILP significantly correlated with a complete tumour response. No
      correlation was found for sarcoma patients. In a comparative analysis we found
      that the overall proEMAP and EMAP-II expression was higher in melanoma as
      compared to sarcoma cases and measurements in cell lines revealed high proEMAP
      expression by melanoma cells. We report high EMAP-II expression by endothelial
      cells and association with macrophages. In addition, macrophages are recruited to
      vessel-remnants after ILP. An upregulation of EMAP-II directly after ILP of
      melanoma patients correlates with and might predict a complete response to TNF
      based ILP. The association of macrophages with EMAP-II expression and vascular
      damage suggests a role for EMAP-II in regulating the TNF-based anti-tumour
      effects observed with an ILP. Analysis of EMAP-II expression in melanoma biopsies
      should be implemented in the ILP procedure.

PMID- 16615115
TI  - Lymphatic and vascular origin of Kaposi's sarcoma spindle cells during tumor
      development.
AB  - The histogenesis of Kaposi's sarcoma (KS) tumor spindle cells (SC) remains
      controversial but several immunohistochemical studies favor a lymphatic origin.
      Twenty KS surgical biopsies were analyzed for the coexpression of LANA, CD34,
      LYVE-1, D2-40, VEGFR-2, VEGFR3 by using double or triple immunostaining. Most of
      the SC in both early and late KS expressed the lymphatic markers LYVE-1, D2-40
      and VEGFR-3 and the blood vascular endothelial/endothelial precursor cell markers
      CD34 and endothelial stem cell marker VEGFR-2. All the LANA+ SC in early and late
      KS were LYVE-1+, but only 75% of these LANA+ cells were CD34(+). The
      CD34(+)/LANA+ cells increased from early- (68.8%) to late-stage KS (82.2%).
      However, approximately 18% of the LANA+ SC in early KS were CD34(-) but were LYVE
      1+, suggesting that resident lymphatic endothelial cells (LEC) are targeted for
      primary infection by human herpesvirus-8. This LANA+/LYVE-1+/CD34(-) (resident
      LEC) cell population clearly decreased during the development of KS from early
      (18.7%) to late KS (2.9%). Thus, in late stages of KS, most SC were
      LANA+/CD34(+)/LYVE-1+. However, in both early- and late-stage KS, approximately
      18% of the SC were CD34(+)/LANA-/LYVE-1 -- and could represent newly recruited
      endothelial precursor cells, which become infected in the lesion and eventually
      undergo a phenotype switch expressing LEC markers. Our study apparently indicates
      that KS represents a unique variant of tumor growth with continues recruitment of
      tumor precursor cells as well as proliferation and decreased apoptosis of SC.

PMID- 16615116
TI  - Folate fortification, plasma folate, homocysteine and colorectal adenoma
      recurrence.
AB  - In 1996, the US Food and Drug Administration mandated the fortification of grain
      products with folic acid, a nutrient that has been associated with lower risk of
      colorectal neoplasia. We assessed the relation of plasma folate and homocysteine
      and colorectal adenoma recurrence separately in 2 studies: the first involved an
      intervention of a cereal supplement that contained folic acid, wheat bran fiber
      (WBF), and the second was conducted primarily during postfortification of the
      food supply using ursodeoxycholic acid (UDCA). Analyses were stratified for
      multivitamin use. Results show that plasma folate and homocysteine concentrations
      were associated with adenoma recurrence among nonusers of multivitamins only.
      Among nonmultivitamin users, the odds ratio [OR] (95% confidence interval [CI])
      for those in the highest versus the lowest folate quartile was 0.65 (0.40-1.06)
      for the WBF study and 0.56 (0.31-1.02) for the UDCA; likewise, individuals in the
      highest versus the lowest quartile of homocysteine had higher odds of adenoma
      recurrence, in both the WBF (OR = 2.25; 95% CI = 1.38-3.66) and UDCA (OR = 1.93;
      95% CI = 1.07-3.49) populations. Analyses comparing multivitamin users to
      different plasma folate concentrations among nonusers show that odds of
      recurrence for supplement users was lower only when compared to nonusers who had
      lower concentrations. Our results show that higher plasma folate or lower
      homocysteine levels are associated with lower odds of recurrence among nonusers
      of multivitamins in both studies. Our finding, suggesting that multivitamins or
      supplemental folate only benefit individuals with lower plasma folate
      concentrations, should be taken into consideration when designing and
      interpreting results of intervention studies.

PMID- 16615117
TI  - Interference with O-glycosylation in RMA lymphoma cells leads to a reduced in
      vivo growth of the tumor.
AB  - Carbohydrate processing in cancer cells can influence the growth, metastatic
      potential, vascularization and immune recognition of such cells. Interference
      with N-glycosylation has been shown both to reduce the membrane expression of MHC
      class I and to increase the in vitro sensitivity of tumor cells to NK cell
      killing. We investigated the effect of O-glycosylation inhibition on the in vivo
      growth, phenotype and NK sensitivity of RMA lymphoma cells using benzyl N-acetyl
      alpha-D-galactosamide (BAG). BAG-treated cells were found to have a strongly
      reduced local growth potential in vivo. However, inhibition of O-glycosylation
      caused this effect without any significant downregulation of MHC-I and increase
      in sensitivity to NK killing as seen after inhibition of N-glycosylation using
      Castanospermine. BAG treatment of RMA cells resulted in the removal of larger O
      linked glycans and a high expression of the T-antigen (GalGalNAc), a target for
      natural antibodies (NAs) induced by the gastrointestinal bacterial flora. Whether
      the loss of larger O-linked glycans, and associated functions, or of biological
      effects of NA contributed to the antitumor effect remains to be established. The
      results support the idea that inhibitors of O- as well as N-linked glycosylation
      may be useful for the treatment of cancer, given that they can be specifically
      targeted to the tumor tissue.

PMID- 16615118
TI  - Microarray analyses in bladder cancer cells: inhibition of hTERT expression down
      regulates EGFR.
AB  - The human telomerase reverse transcriptase (hTERT) contributes to the immortal
      phenotype of the majority of cancers. Targeting hTERT by transfection with
      antisense oligonucleotides (AS-ODNs) induced immediate growth inhibition in human
      bladder cancer (BCa) cells. The molecular basis of the antiproliferative capacity
      of hTERT AS-ODNs was investigated by oligonucleotide microarray analyses and was
      compared to effects caused by siRNA-mediated knock-down of hTERT in EJ28 BCa
      cells. Two different AS-ODNs -- both down-regulated the expression of hTERT --
      changed the expression of different genes mainly involved in stress response
      (including EGR1, ATF3 and GDF15), but without an association to telomerase
      function. This indicates that the immediate growth inhibition was caused, at
      least in part, by off-target effects. In comparison to that the blockade of the
      expression of hTERT using 2 different siRNAs was accompanied by the down
      regulation of the oncogenes FOS-like antigen 1 (FOSL1) and epidermal growth
      factor receptor (EGFR), known to be overexpressed in BCa. We show here for the
      first time that repression of the hTERT transcript number decreased the
      expression of EGFR both at the mRNA and protein levels, suggesting a potential
      new function of hTERT in the regulation of EGFR-stimulated proliferation.
      Furthermore, the suppression of hTERT by siRNAs caused an enhancement of the
      antiproliferative capacity of the chemotherapeutics mitomycin C and cisplatin.
      The results presented herein may support the hypothesis that hTERT promotes the
      growth of tumor cells by mechanisms independent from telomere lengthening. The
      detailed clarification of these processes will shed light on the question,
      whether telomerase inhibitors might constitute suitable anticancer tools.

PMID- 16615119
TI  - Diagnosis of single-subject and group fMRI data with SPMd.
AB  - Except for purely nonparametric methods, statistical methods depend on
      assumptions about the distribution of the data studied. While these assumptions
      are easily checked for a single univariate dataset with diagnostic plots, in the
      massively univariate model used with functional MRI (fMRI) it is impractical to
      check with a massive number of plots. In previous work we have demonstrated how
      to diagnose model assumptions and lack-of-fit for single-subject fMRI models
      using a working assumption of independent errors; our work depended on images and
      time series of summary statistics that, when simultaneously viewed dynamically,
      identify problem scans and voxels. In this article we extend our previous work to
      account for temporal autocorrelation in single-subject models and show how
      analogous methods can be used on group models where multiple subjects are
      studied. We apply these methods to the single-subject Functional Image Analysis
      Contest (FIAC) data and find several anomalies, but none that appear to
      invalidate the results for that subject. With the group FIAC data we find one
      subject (and possibly two more) that demonstrate a different pattern of activity.
      None of our conclusions would be arrived at by simply looking at images of t
      statistics, demonstrating the importance of model assessment through exploration
      of the data and diagnosis of model assumptions.

PMID- 16615120
TI  - Synaptic organization of projections from the amygdala to visual cortical areas
      TE and V1 in the macaque monkey.
AB  - The primate amygdaloid complex projects to a number of visual cortices, including
      area V1, primary visual cortex, and area TE, a higher-order unimodal visual area
      involved in object recognition. We investigated the synaptic organization of
      these projections by injecting anterograde tracers into the amygdaloid complex of
      Macaca fascicularis monkeys and examining labeled boutons in areas TE and V1
      using the electron microscope. The 256 boutons examined in area TE formed 263
      synapses. Two hundred twenty-three (84%) of these were asymmetric synapses onto
      dendritic spines and 40 (15%) were asymmetric synapses onto dendritic shafts.
      Nine boutons (3.5%) formed double asymmetric synapses, generally on dendritic
      spines, and 2 (1%) of the boutons did not form a synapse. The 200 boutons
      examined in area V1 formed 211 synapses. One hundred eighty-nine (90%) were
      asymmetric synapses onto dendritic spines and 22 (10%) were asymmetric synapses
      onto dendritic shafts. Eleven boutons (5.5%) formed double synapses, usually with
      dendritic spines. We conclude from these observations that the amygdaloid complex
      provides an excitatory input to areas TE and V1 that primarily influences spiny,
      probably pyramidal, neurons in these cortices.

PMID- 16615122
TI  - Developmental pattern of CB1 cannabinoid receptor immunoreactivity in brain
      regions important to zebra finch (Taeniopygia guttata) song learning and control.
AB  - Zebra finches learn song during distinct developmental stages, making them an
      important species for studying mechanisms underlying vocal development. Distinct
      interconnected forebrain regions have been identified as important to specific
      features of zebra finch vocal learning and production. Because prior experiments
      have demonstrated that late postnatal exposure to cannabinoid agonists alters
      zebra finch song learning, we have sought to identify brain regions likely
      involved in it. By using an affinity-purified polyclonal antibody directed
      against the zebra finch CB(1) cannabinoid receptor, we have studied staining
      patterns in groups of males at 25, 50, 75, and >100 days of age (adults). A
      general waxing and waning of staining intensity were observed over this
      developmental period. Distinct staining of song-related brain regions was also
      noted. Early establishment of staining patterns within rostral telencephalic song
      regions [area X and lateral magnocellular nucleus of the anterior nidopallium
      (lMAN)] suggests a role in auditory learning. Later establishment and maintenance
      in adulthood of small somata and neuropil staining within regions of rostral
      telencephalon [HVC and robust nucleus of the arcopallium (RA)] are consistent
      with a vocal motor role for cannabinoid signaling. Our results provide insight
      into brain regions likely responsible for cannabinoid-altered vocal learning and
      add to accumulating evidence supporting an important role for cannabinoid
      signaling in CNS development.

PMID- 16615121
TI  - Subpopulations of neurons expressing parvalbumin in the human amygdala.
AB  - Amygdalar intrinsic inhibitory networks comprise several subpopulations of gamma
      aminobutyric acidergic neurons, each characterized by distinct morphological
      features and clusters of functionally relevant neurochemical markers. In rodents,
      the calcium-binding proteins parvalbumin (PVB) and calbindin D28k (CB) are
      coexpressed in large subpopulations of amygdalar interneurons. PVB-immunoreactive
      (-IR) neurons have also been shown to be ensheathed by perineuronal nets (PNN),
      extracellular matrix envelopes believed to affect ionic homeostasis and synaptic
      plasticity. We tested the hypothesis that differential expression of these three
      markers may define distinct neuronal subpopulations within the human amygdala.
      Toward this end, triple-fluorescent labeling using antisera raised against PVB
      and CB as well as biotinylated Wisteria floribunda lectin for detection of PNN
      was combined with confocal microscopy. Among the 1,779 PVB-IR neurons counted,
      18% also expressed CB, 31% were ensheathed in PNN, and 7% expressed both CB and
      PNN. Forty-four percent of PVB-IR neurons did not colocalize with either CB or
      PNN. The distribution of each of these neuronal subgroups showed substantial
      rostrocaudal gradients. Furthermore, distinct morphological features were found
      to characterize each neuronal subgroup. In particular, significant differences
      relative to the distribution and morphology were detected between PVB-IR neurons
      expressing CB and PVB-IR neurons wrapped in PNNs. These results indicate that
      amygdalar PVB-IR neurons can be subdivided into at least four different
      subgroups, each characterized by a specific neurochemical profile, morphological
      characteristics, and three-dimensional distribution. Such properties suggest that
      each of these neuronal subpopulations may play a specific role within the
      intrinsic circuitry of the amygdala.

PMID- 16615123
TI  - P2X2 receptors on ganglion and amacrine cells in cone pathways of the rat retina.
AB  - Extracellular ATP is known to mediate fast, excitatory neurotransmission through
      activation of ionotropic P2X receptors. In this study, the localization of the
      P2X(2) receptor (P2X(2)R) subunit was studied in rat retina by using
      immunofluorescence immunohistochemistry and preembedding immunoelectron
      microscopy. The P2X(2)R was observed in large ganglion cells as well as in a
      subset of amacrine cells. Double labeling revealed that 96% of all P2X(2)R
      immunoreactive amacrine cells showed gamma-aminobutyric acid (GABA)
      immunoreactivity. Subsets of P2X(2)R-immunoreactive amacrine cells expressed
      nitric oxide synthase and substance P; however, no colocalization was observed
      with choline acetyltransferase, vasoactive intestinal peptide, or tyrosine
      hydroxylase. Nearest-neighbor analysis confirmed that P2X(2)Rs were expressed by
      a heterogeneous population of amacrine cells. The synaptic connectivity of
      P2X(2)R amacrine cells was also investigated. It was interesting that P2X(2)R
      immunoreactive amacrine cell dendrites stratified in the sublaminae of the inner
      plexiform layer occupied by cone, but not rod bipolar cell axon terminals.
      Immunoelectron microscopy revealed that P2X(2)-immunoreactive amacrine cell
      processes were associated with cone bipolar cell axon terminals as well as other
      conventional synapses in the inner plexiform layer. Taken together, these data
      provide further evidence for the involvement of extracellular ATP in neuronal
      signaling in the retina, particularly within cone pathways.

PMID- 16615124
TI  - EphA7-ephrin-A5 signaling in mouse somatosensory cortex: developmental
      restriction of molecular domains and postnatal maintenance of functional
      compartments.
AB  - Members of the Eph family of receptor tyrosine kinases and their ligands, the
      ephrins, are expressed in distinct patterns in the forming cortex. EphA7 is
      expressed early in cortical development, becoming concentrated in anterior and
      posterior domains, whereas ephrin-A5 is expressed later in corticogenesis,
      highest in the middle region that has low levels of EphA7. The EphA7 gene
      produces full-length and truncated isoforms, which are repulsive and adhesive,
      respectively. Analysis of cortical RNA expression demonstrates that proportions
      of these isoforms change with time, from a more repulsive mix during
      embryogenesis to a more permissive mix postnatally. To examine how EphA7 and
      ephrin-A5 influence the formation of cortical regions, EphA7-/- mice were
      analyzed. Within the cortex of EphA7-/- mice, the distribution of ephrin-A5 was
      more extensive, encompassing its usual medial domain but also extending more
      posteriorly toward the occipital pole. Moreover, relative levels of ephrin-A5
      along the cortex's anatomical axes changed in EphA7-/- animals, creating less
      striking shifts in ligand abundance. Furthermore, in vivo functional studies
      revealed that EphA7 exerts a repulsive influence on ephrin-A5-expressing cells
      during corticogenesis. In contrast, EphA7 appears to mediate permissive
      interactions in the postnatal cortex: the area of somatosensory cortex was
      significantly reduced in EphA7-/- mice. A similar reduction was present in ephrin
      A5-/- animals and a more pronounced decrease was observed in EphA7/ephrin-A5-/-
      cortex. Taken together, this study supports a role for EphA7 and ephrin-A5 in the
      establishment and maintenance of certain cortical domains and suggests that the
      nature of their interactions changes with cortical maturity.

PMID- 16615125
TI  - Organization of noradrenergic efferents to arousal-related basal forebrain
      structures.
AB  - Norepinephrine acts within select basal forebrain regions to modulate behavioral
      state and/or state-dependent processes, including the general regions
      encompassing the medial septal area, the medial preoptic area, and the substantia
      innominata. The present study examined the origin and organization of
      noradrenergic efferents to these basal forebrain regions by using combined
      immunohistochemical identification of noradrenergic neurons with retrograde
      tracing. Results indicate that the locus coeruleus provides the majority of
      noradrenergic input to these regions. Lesser, although at times substantial,
      contributions from the A1/C1 and A2/C2 adrenergic cell groups were also observed,
      particularly in the case of the medial preoptic region. Given the prominent state
      modulating actions of the locus coeruleus, additional studies examined: 1)
      lateralization of locus coeruleus efferents to these regions; 2) the
      topographical organization of basal forebrain-projecting locus coeruleus neurons;
      and 3) the degree of collateralization of individual locus coeruleus neurons
      across these regions. Approximately 80-85% of locus coeruleus efferents to these
      regions project ipsilaterally. In general, basal forebrain-projecting neurons
      were distributed throughout the entire dorsoventral and rostrocaudal extent of
      the locus coeruleus. Additionally, a large proportion of locus coeruleus neurons
      project simultaneously to these basal forebrain terminal fields. Combined, these
      observations indicate coordinated actions of locus coeruleus neurons across these
      basal forebrain regions implicated in the regulation of behavioral state and/or
      state-dependent processes.

PMID- 16615126
TI  - Comprehensive analysis of the expression patterns of the adenylate cyclase gene
      family in the developing and adult mouse brain.
AB  - Adenylate cyclases (Adcys) are components of several developmentally,
      neurophysiologically, and pharmacologically relevant signaling pathways. A
      prominent feature of Adcys is their ability to integrate multiple signaling
      pathways into a single second messenger pathway, the production of cAMP. Nine
      isoforms of membrane-bound Adcys are known, each encoded by a distinct gene.
      These isoforms differ in their response to regulatory upstream pathways as well
      as in their distribution in the brain and elsewhere. Use of various detection
      methods and animal species has, however, hampered a direct comparison of
      expression patterns, so the potential contribution of single isoforms to Adcy
      activity in different brain regions remains unclear. We have determined the
      expression patterns of all nine Adcy genes in the embryonic, postnatal day 7, and
      adult mouse brain by nonradioactive robotic in situ hybridization (ISH). Here we
      describe the salient features of these patterns. Regional colocalization of Adcy
      transcripts encoding isoforms with different regulatory properties was detected
      in the cortex, subregions of the hippocampus, olfactory bulb, thalamus, and
      striatum. Hence, our expression data support models for modulation of cAMP
      signaling by combinatorial action of multiple Adcy isoforms. However, in several
      instances, the expression domains of genes encoding isoforms with similar
      regulatory properties spatially exclude each other, which is most evident in not
      previously described expression domains of the embryonic midbrain roof. This is
      suggestive of functional specialization.

PMID- 16615127
TI  - Lateral components in the cone terminals of the rabbit retina: horizontal cell
      origin and glutamate receptor expression.
AB  - We examined the identities of horizontal cell (HC) lateral components in cone
      terminals and the expression of glutamate receptors on the tips of HC dendrites.
      We injected A-type horizontal cells (AHCs) with neurobiotin and demonstrated that
      neurobiotin labeled completely all AHCs within a patch of retina. We converted
      neurobiotin by using diaminobenzidine and considered labeled processes to be from
      AHCs and unlabeled processes to be from B-type horizontal cells (BHCs). Three
      possible combinations of HC dendrites could exist in cone pedicles: both lateral
      components originating from AHCs, both from BHCs, or one from an AHC and the
      other from a BHC. EM observations revealed that a majority of cone terminals
      contained about equal numbers of lateral components originating from each of the
      two types of HCs and that each of the three possible combinations was present in
      equal numbers. Localization of different types of glutamate receptors on HC
      dendritic tips showed that 55% of AHC dendritic tips expressed AMPA receptors and
      30% expressed kainate receptors, whereas, in the case of BHCs, 22% of dendritic
      tips expressed AMPA receptors and 33% expressed kainate receptors. This study
      suggests that cone photoreceptors feed the light signal equally into networks of
      AHCs and BHCs and that differential expression of AMPA/kainate receptors by
      different HCs could account for different functions.

PMID- 16615130
TI  - Distribution of substance P reveals a novel subdivision in the hippocampus of
      parasitic South American cowbirds.
AB  - Parasitic cowbirds monitor potential hosts' nests and return to lay when
      appropriate, a task that is likely to involve spatial recall. Seasonal and sexual
      behavioral variations in the cowbirds correlate with anatomical changes in the
      hippocampal formation. During the breeding season, parasites have larger
      hippocampal formations than nonparasites. In parasitic species in which females
      alone perform nest bookkeeping, females have larger hippocampal formations than
      males. We investigated the distribution of the neuropeptide substance P (SP) in
      three sympatric cowbirds: two obligate parasites (shiny cowbird and screaming
      cowbird) and one nonparasite (bay-winged cowbird). Distribution of SP was similar
      to that in other songbirds, except for a previously undescribed field of dense SP
      rich terminals within the hippocampus that we call the hippocampal SP terminal
      field (SPh). We found robust species differences in the volume of this new area,
      measured relative to the remainder of the telencephalon. SPh was largest in the
      generalist parasite (shiny cowbird) and smallest in the nonparasitic species (bay
      winged cowbird). In the specialist parasite (screaming cowbird), SPh was smaller
      than in the generalist parasite but larger than in the nonparasitic species. SPh
      overlaps with two subdivisions described in the pigeon that have been related to
      the mammalian dentate gyrus and subiculum. The area containing SPh receives a
      major input from the lateral mammillary nucleus, which is probably the avian
      equivalent of the mammalian supramammillary nucleus (SUM), the main source of
      extrinsic SP input to mammalian hippocampus. SPh may be the termination of a
      pathway homologous to the SP-rich projection from SUM to the hippocampus in
      mammals.

PMID- 16615131
TI  - "Mir"acles in hox gene regulation.
AB  - Micro RNAs (miRNAs) have been shown to control many cellular processes including
      developmental timing in different organisms. The prediction that miRNAs are
      involved in regulating hox genes of flies and mouse is quite a recent idea and is
      supported by the finding that mir-196 represses Hoxb8 gene expression. The non
      coding regions that encode these miRNAs are also conserved across species in the
      same way as other mechanisms that regulate expression of hox genes. On the
      contrary, until now no homeotic phenotype, a hallmark of any hox gene mutation,
      had been associated with any hox miRNA. Recent work on bithorax complex miRNA
      (miR-iab-4-5p) shows, for the first time, that miRNAs can lead to homeotic
      transformation. This miRNA regulates Ultrabithorax (Ubx) and results in the
      transformation of haltere to wing. This study unveils a new complexity and
      finesse to the regulation of hox gene expression pattern that is needed for
      determining the anteroposterior body axis in all bilaterians.

PMID- 16615128
TI  - Sex differences in the anatomical and functional organization of the
      periaqueductal gray-rostral ventromedial medullary pathway in the rat: a
      potential circuit mediating the sexually dimorphic actions of morphine.
AB  - Previous studies have demonstrated that morphine, administered systemically or
      directly into the periaqueductal gray (PAG), produces a significantly greater
      degree of antinociception in males in comparison with females. Because the
      midbrain PAG and its descending projections to the rostral ventromedial medulla
      (RVM) constitute an essential neural circuit for opioid-based analgesia, the
      present studies were conducted to determine whether sex differences in the
      anatomical organization of the PAG-RVM pathway, and its activation during
      persistent inflammatory pain, could account for sex-based differences in opioid
      analgesia. In the rat, retrograde tracing was combined with Fos
      immunocytochemistry to investigate sexual dimorphism in the organization of the
      PAG-RVM circuit and its activation by persistent inflammatory pain induced by
      intraplantar injection of complete Freund's adjuvant (CFA). The ability of
      morphine to suppress the activation of the PAG-RVM circuit was also examined.
      Sexually dimorphic retrograde labeling was observed within the dorsomedial and
      lateral/ventrolateral PAG at all rostrocaudal levels, with females having
      significantly more PAG-RVM output neurons in comparison with males. While no sex
      differences were noted in the activation of the PAG by persistent inflammatory
      pain, significantly more PAG-RVM cells were activated in males in comparison with
      females. Systemic administration of morphine significantly suppressed CFA-induced
      Fos in the PAG in males only. The results of these studies demonstrate that both
      the anatomical organization and the functional activation of the PAG-RVM circuit
      are sexually dimorphic and may provide the anatomical substrate for sex-based
      differences in morphine analgesia.

PMID- 16615129
TI  - Dynamic expression of retinoic acid-synthesizing and -metabolizing enzymes in the
      developing mouse inner ear.
AB  - Retinoic acid signaling plays essential roles in morphogenesis and neural
      development through transcriptional regulation of downstream target genes. It is
      believed that the balance between the activities of synthesizing and metabolizing
      enzymes determines the amount of active retinoic acid to which a developing
      tissue is exposed. In this study, we investigated spatiotemporal expression
      patterns of four synthesizing enzymes, the retinaldehyde dehydrogenases 1, 2, 3,
      and 4 (Raldh1, Raldh2, Raldh3, and Raldh4) and two metabolizing enzymes (Cyp26A1
      and Cyp26B1) in the embryonic and postnatal mouse inner ear by using quantitative
      reverse transcriptase polymerase chain reaction (RT-PCR), in situ hybridization,
      and Western blot analysis. Quantitative RT-PCR analysis and Western blot data
      revealed that the expression of CYP26s was much higher than that of Raldhs at
      early embryonic ages but that Cyp26 expression was downregulated during embryonic
      development. Conversely, the expression levels of Raldh2 and -3 increased during
      development and were significantly higher than the Cyp26 levels at postnatal day
      20. At this age, Raldh3 was expressed predominantly in the cochlea, whereas
      Raldh2 was present in the vestibular end organ. At early embryonic stages, as
      observed by in situ hybridization, the synthesizing enzymes were expressed only
      in the dorsoventral epithelium of the otocyst, whereas the metabolizing enzymes
      were present mainly in mesenchymal cells surrounding the otic epithelium. At
      later stages, Raldh2, Raldh3, and Cyp26B1 were confined to the stria vascularis,
      spiral ganglion, and supporting cells in the cochlear and vestibular epithelia,
      respectively. The downregulation of Cyp26s and the upregulation of Raldhs after
      birth during inner ear maturation suggest tissue changes in the sensitivity to
      retinoic acid concentrations.

PMID- 16615132
TI  - Microvascular blood flow dynamics associated with photodynamic therapy, pulsed
      dye laser irradiation and combined regimens.
AB  - BACKGROUND AND OBJECTIVES: Previous in vitro studies demonstrated the potential
      utility of benzoporphyrin derivative monoacid ring A (BPD) photodynamic therapy
      (PDT) for vascular destruction. Moreover, the effects of PDT were enhanced when
      this intervention was followed immediately by pulsed dye laser (PDL) irradiation
      (PDT/PDL). We further evaluate vascular effects of PDT alone, PDL alone and
      PDT/PDL in an in vivo rodent dorsal skinfold model. STUDY DESIGN/MATERIALS AND
      METHODS: A dorsal skinfold window chamber was installed surgically on female
      Sprague-Dawley rats. One milligram per kilogram of BPD solution was administered
      intravenously via a jugular venous catheter. Evaluated interventions were:
      control (no BPD, no light), PDT alone (576 nm, 16 minutes exposure time, 15
      minutes post-BPD injection, 10 mm spot), PDL alone at 7 J/cm2 (585 nm, 1.5 ms
      pulse duration, 7 mm spot), PDL alone at 10 J/cm2, PDT/PDL (PDL at 7 J/cm2), and
      PDT/PDL (PDL at 10 J/cm2). To assess changes in microvascular blood flow, laser
      speckle imaging was performed before, immediately after, and 18 hours post
      intervention. RESULTS: Epidermal irradiation was accomplished without blistering,
      scabbing or ulceration. A reduction in perfusion was achieved in all intervention
      groups. PDT/PDL at 7 J/cm2 resulted in the greatest reduction in vascular
      perfusion (56%). CONCLUSIONS: BPD PDT can achieve safe and selective vascular
      flow reduction. PDT/PDL can enhance diminution of microvascular blood flow. Our
      results suggest that PDT and PDT/PDL should be evaluated as alternative
      therapeutic options for treatment of hypervascular skin lesions including port
      wine stain birthmarks.

PMID- 16615133
TI  - Fluorescence staining of human ovarian cancer tissue following application of 5
      aminolevulinic acid: fluorescence microscopy studies.
AB  - BACKGROUND AND OBJECTIVES: Application of 5-aminolevulinic acid (ALA) for
      fluorescence-guided second-look laparoscopy has been shown to be a promising new
      procedure in the early diagnosis of ovarian carcinoma metastases. However, for
      assessing the reliability of this method, information on the microscopic
      distribution of protoporphyrin IX (PP IX) in the tissue is needed. Additionally,
      the selectivity of PP IX uptake is essential for a potential photodynamic therapy
      (PDT) of ovarian cancer metastases. STUDY DESIGN/MATERIALS AND METHODS: Thirty
      six patients with epithelial ovarian cancer and two patients suffering from
      fallopian tube carcinoma underwent a laparoscopic second-look procedure 5 hours
      after the application of ALA. In 17 patients 36 fluorescence-guided biopsies were
      taken from fluorescing and non-fluorescing tissues for further evaluation.
      Fluorescence microscopy and digital image processing were utilized to determine
      the presence of PP IX fluorescence. RESULTS: A specificity of 88% and a
      sensitivity of 100% with a negative predictive value of 100% and a positive
      predictive value of 91% were calculated for PP IX fluorescence on a microscopic
      level as marker for ovarian cancer metastases. CONCLUSIONS: On a microscopic
      scale, ALA-induced PP IX fluorescence is confined to ovarian cancer tumor tissue
      sparing stromal tissues.

PMID- 16615134
TI  - Absorption of diode 810 nm used for transpupillary thermotherapy by blood. An in
      vitro study.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the in vitro energy attenuation by
      transpupillary thermotherapy (TTT) using an 810-nm diode laser after the
      treatment of exudative age-related macular degeneration. STUDY DESIGN/MATERIALS
      AND METHODS: In this experiment, an 810-nm diode laser was coupled to a slit lamp
      to deliver laser energy to a laser-power sensor adjusted in the track of the
      laser light. The spotlight was 0.5 mm in diameter; duration of exposure, 3
      seconds. Citrated Pasteur pipettes were filled with blood diluted in saline in
      several concentrations and placed in the path of the laser light. The absorption
      of the light measured by the power sensor was tested for various delivered
      irradiances between 50.92 and 509.29 W/cm2. The differences were analyzed
      statistically. RESULTS: There were significant differences in laser blockage
      comparing various conditions for all power levels (P<0.05). Increasing the
      proportion of blood resulted in more laser blockage with all irradiances
      (P<0.05). CONCLUSIONS: Blood significantly blocks the transmission of the 810-nm
      diode TTT laser.

PMID- 16615135
TI  - Initiation of apoptosis and autophagy by photodynamic therapy.
AB  - BACKGROUND AND OBJECTIVES: This study was designed to examine modes of cell death
      after photodynamic therapy (PDT). STUDY DESIGN: Murine leukemia L1210 cells and
      human prostate Bax-deficient DU145 cells were examined after PDT-induced
      photodamage to the endoplasmic reticulum (ER). Phase contrast, fluorescence and
      electron microscopy were used to identify changes in cellular morphology,
      chromatin condensation, loss of mitochondrial membrane potential, and formation
      of phagolysosomes. Western blots were used to assess the processing of LC3-I to
      LC3-II, a marker for autophagy. Inhibitors of apoptosis and/or autophagy were
      used to delineate the contributions of the two pathways to the effects of PDT.
      RESULTS: Both apoptosis and autophagy occurred in L1210 after ER photodamage with
      the latter predominating after 24 hours. In DU145 cells, PDT conditions causing
      comparable cytotoxicity only initiated autophagy. PI3-kinase inhibitors
      suppressed autophagy in both cell lines as indicated by inhibition of
      vacuolization and LC3 processing. CONCLUSIONS: Both autophagy and apoptosis were
      observed in L1210 cells following ER photodamage. In the Bax-deficient DU145 cell
      line only autophagy was observed. Current information suggests that autophagy can
      function as either a survival or death pathway. We propose that in the context of
      PDT, this may also be true.

PMID- 16615136
TI  - Fluence rate as a modulator of PDT mechanisms.
AB  - BACKGROUND AND OBJECTIVES: Molecular oxygen in the tissue to be treated by
      photodynamic therapy (PDT) is critical for photodynamic cell killing. The fluence
      rate of PDT light delivery has been identified as an important modulator of
      tissue oxygenation and treatment outcome. This article provides supporting
      evidence for the role of fluence rate in PDT and discusses the underlying
      mechanisms. STUDY DESIGN/MATERIALS AND METHODS: Intratumoral pO2 was measured
      polarographically in murine tumors before and during PDT light treatment using
      the Eppendorf pO2 Histograph. Tumor response as a function of fluence rate and
      fluence was also assessed in murine tumor models. Changes in vascular
      permeability as a function of fluence rate were determined in murine tumors by
      measuring tumor uptake of fluorescent beads (200 nm diameter). RESULTS: Severe
      oxygen depletion is shown to occur within seconds of illumination at a fluence
      rate of 75 mW/cm2 in radiation-induced fibrosarcoma (RIF) tumors photosensitized
      with AlPcS2. This effect was reversible and consistent with photochemical oxygen
      depletion, which has been shown by us and others to be fluence rate dependent. It
      is demonstrated that fluence rate affects the PDT tumor response in the Colon 26
      tumor model, high fluence rate diminishing or even totally inhibiting tumor
      control, low fluence rate promoting tumor control. The influence of fluence rate
      is not restricted to cytocidal effects, but can also be seen in sublethal
      conditions such as vascular permeability. CONCLUSIONS: Fluence rate of PDT light
      delivery exerts far-reaching control upon treatment outcome through its
      oxygenation modulating properties and possibly other mechanisms yet to be
      identified. This has been shown to be true in the preclinical and clinical
      setting. Further development of in situ dosimetry will be necessary to take full
      advantage of these discoveries.

PMID- 16615137
TI  - Distribution of neuromuscular junctions in laryngeal and syringeal muscles in
      vertebrates.
AB  - Vertebrates are capable of producing a variable sound spectrum. In mammals,
      lissamphibia, and reptiles, the larynx is the vocal organ responsible for sound
      production, whereas in birds it is produced by the syrinx, an avian organ located
      at the base of trachea. The distribution of neuromuscular junctions responsible
      for the fine control of laryngeal muscle (LM) and syringeal muscle (SM), although
      studied with some detail in human LM, remains mostly unknown in other
      vertebrates. In the present study, we analyzed the distribution of motor end
      plates (MEPs) in LM/SM of different vertebrate classes using the histochemical
      detection of acetylcholinesterase: the thyroarytenoid and cricoarytenoid LM of
      mammal (human, rat, and rabbit) and cricoarytenoid LM of nonmammalian (frog and
      avian) species and the tracheobronchial SM of rooster and pigeon. In humans and
      frogs/avians, MEPs were distributed diffusely along, respectively, the
      thyroarytenoid-cricoarytenoid and the cricoarytenoid LM fibers, whereas in rats
      and rabbits, MEPs were concentrated in a transverse band located in the middle of
      thyroarytenoid and cricoarytenoid muscle fibers. In roosters and pigeons, MEPs
      were distributed diffusely along SM fibers. The highly diffuse MEP distribution
      along human thyroarytenoid and cricoarytenoid fibers indicates that these muscles
      can markedly change their degree of contraction, which may contribute for the
      large range of different sounds produced by human vocal folds. The same rationale
      was applied to discuss the possible functional significance of the morphological
      distribution of MEPs along the LM/SM of the other vertebrates analyzed.

PMID- 16615138
TI  - Effect of methylglyoxal modification and phosphorylation on the chaperone and
      anti-apoptotic properties of heat shock protein 27.
AB  - Heat shock protein 27 (Hsp27) is a stress-inducible protein in cells that
      functions as a molecular chaperone and also as an anti-apoptotic protein.
      Methylglyoxal (MGO) is a reactive dicarbonyl compound produced from cellular
      glycolytic intermediates that reacts non-enzymatically with proteins to form
      products such as argpyrimidine. We found considerable amount of Hsp27 in
      phosphorylated form (pHsp27) in human cataractous lenses. pHsp27 was the major
      argpyrimidine-modified protein in brunescent cataractous lenses. Modification by
      MGO enhanced the chaperone function of both pHsp27 and native Hsp27, but the
      effect on Hsp27 was at least three-times greater than on pHsp27. Phosphorylation
      of Hsp27 abolished its chaperone function. Transfer of Hsp27 using a cationic
      lipid inhibited staurosporine (SP)-induced apoptotic cell death by 53% in a human
      lens epithelial cell line (HLE B-3). MGO-modified Hsp27 had an even greater
      effect (62% inhibition). SP-induced reactive oxygen species in HLE-B3 cells was
      significantly lower in cells transferred with MGO-modified Hsp27 when compared to
      native Hsp27. In vitro incubation experiments showed that MGO-modified Hsp27
      reduced the activity of caspase-9, and MGO-modified pHsp27 reduced activities of
      both caspase-9 and caspase-3. Based on these results, we propose that Hsp27
      becomes a better anti-apoptotic protein after modification by MGO, which may be
      due to multiple mechanisms that include enhancement of chaperone function,
      reduction in oxidative stress, and inhibition of activity of caspases. Our
      results suggest that MGO modification and phosphorylation of Hsp27 may have
      important consequences for lens transparency and cataract development.

PMID- 16615139
TI  - Analysis of individual data from bead-based assays ("bead arrays").
AB  - INTRODUCTION: Typically, bead-based assays ("bead arrays") use the mean or median
      value of a population of measurements to judge ligand binding or other activity,
      which results in a change in fluorescence intensity. Individual bead measurements
      are used here to calculate population parameters integral to the measurement of a
      bead array. METHODS: Using a commercially-available instrument designed for bead
      array measurements, a set of beads were labeled with biotin and then titrated
      with PE-Streptavidin. Data were collected under normal machine conditions as well
      as variations. RESULTS: The "sensitivity" of the measurements was determined
      using parametric and nonparametric statistical methods as well as regression
      analysis over a limited range of the titration (concentration vs. response
      profile). CONCLUSIONS: Results at low ligand concentrations suggest that precise
      measurements with bead array systems require a large number of individual bead
      measurements to be acquired. Individual bead measurements should be used to
      determine the mean and confidence intervals for the calculated measurements.
      These results also apply to regression analysis of concentration-response
      profiles. Furthermore, features of the instrument can be manipulated to achieve
      increased sensitivity and detection of lower amounts of ligand bound to the bead
      populations.

PMID- 16615140
TI  - Imaging spectrometer fundamentals for researchers in the biosciences--a tutorial.
AB  - Over the last 2 years there has been a dramatic increase in the number of
      bioscience laboratories using wavelength dispersive spectroscopy to study in
      vivo, in situ fluorescence. Transforming spectral information into an image
      provides a graphic means of mapping localized ionic, molecular, and protein
      protein interactions. Spectroscopy also enables fluorophores with overlapping
      spectral features to be delineation. In this study, we provide the tools that a
      researcher needs to put into perspective instrumental contributions to a reported
      spectrum in order to gain greater understanding of the natural emission of the
      sample. We also show how to deduce the basic capabilities of a spectral confocal
      system. Finally, we show how to determine the true spectral bandwidth of an
      object, the illuminated area of a laser-excited object, and what is needed to
      optimize light throughput.

PMID- 16615141
TI  - Disulfide connectivity prediction with 70% accuracy using two-level models.
AB  - Disulfide bridges stabilize protein structures covalently and play an important
      role in protein folding. Predicting disulfide connectivity precisely helps
      towards the solution of protein structure prediction. Previous methods for
      disulfide connectivity prediction either infer the bonding potential of cysteine
      pairs or rank alternative disulfide bonding patterns. As a result, these methods
      encode data according to cysteine pairs (pair-wise) or disulfide bonding patterns
      (pattern-wise). However, using either encoding scheme alone cannot fully utilize
      the local and global information of proteins, so the accuracies of previous
      methods are limited. In this work, we propose a novel two-level framework to
      predict disulfide connectivity. With this framework, both the pair-wise and
      pattern-wise encoding schemes are considered. Our models were validated on the
      datasets derived from SWISS-PROT 39 and 43, and the results demonstrate that our
      models can combine both local and global information. Compared to previous
      methods, significant improvements were obtained by our models. Our work may also
      provide insights to further improvements of disulfide connectivity prediction and
      increase its applicability in protein structure analysis and prediction.

PMID- 16615142
TI  - Cloning and expression of a Melanocarpus albomyces steryl esterase gene in Pichia
      pastoris and Trichoderma reesei.
AB  - The ste1 gene encoding a steryl esterase was isolated from the thermophilic
      fungus Melanocarpus albomyces. The gene has one intron, and it encodes a protein
      consisting of 576 amino acids. The deduced amino acid sequence of the steryl
      esterase was shown to be related to lipases and other esterases such as
      carboxylesterases. Formation of mature protein requires post-translational
      removal of a putative 18-amino-acid signal sequence and a 13-residue propeptide
      at the N-terminus. The intronless version of the Melanocarpus albomyces ste1 gene
      was expressed in Pichia pastoris under the inducible AOX1 promoter. The
      production level was low, and a large proportion of the total activity yield was
      found to be present intracellularly. However, the fact that steryl esterase
      activity was produced by P. pastoris cells carrying the expression cassette
      confirmed that the correct gene had been cloned. The ste1 gene was subsequently
      expressed in T. reesei under the inducible cbh1 promoter, and a clearly higher
      production level was obtained. About 60% of the total activity was bound to the
      fungal mycelium or to solid components of the culture medium, or existed as
      aggregates. Triton X-100 was successfully used to recover this activity. The
      heterologous production system in T. reesei provides a means of producing M.
      albomyces steryl esterase STE1 reliably in large scale for future studies.

PMID- 16615143
TI  - Biological hydrogen production in a UASB reactor with granules. I:
      Physicochemical characteristics of hydrogen-producing granules.
AB  - Hydrogen-producing granules with an excellent settling ability were cultivated in
      an upflow anaerobic sludge blanket reactor treating a sucrose-rich synthetic
      wastewater. The physicochemical characteristics of granules were evaluated in
      this study. The mature granules had a diameter ranging from 1.0 to 3.5 mm and an
      average density of 1.036 +/- 0.005 g/mL, whereas they had good settling ability
      and a high settling velocity of 32-75 m/h. The low ratio of
      proteins/carbohydrates for the extracellular polymeric substances (EPS) in the
      granules suggests that carbohydrates rather than proteins, might play a more
      important role in the formation of the H(2)-producing granules. The contact angle
      of the mature granules, 54 +/- 2 degrees , was larger than that of the seed
      sludge (38 +/- 2 degrees ), indicating that the microbial cells in the H(2)
      producing granules had higher hydrophobicity. The granules had fractal nature
      with a fractal dimension of 1.78. Their porosities were in the range of 0-0.70,
      and increased with increasing granule size. The ratios between the observed and
      predicted settling velocities by Stokes' law were in a range of 1.00-1.50, and
      the fluid collection efficiency of the granules ranged from 0 to 0.19, indicating
      that their permeabilities were lower and that there was little advective flow
      through their interior. Experimental results also suggest that molecular
      diffusion appeared to play an important role in the mass transfer through the
      H(2)-producing granules.

PMID- 16615144
TI  - Purification of plasmid DNA with polymer-salt aqueous two-phase system:
      optimization using response surface methodology.
AB  - An experimental design was used to optimize plasmid purification from an alkaline
      lysate of Escherichia coli cells using PEG-sodium citrate aqueous two-phase
      systems (ATPS), and to evaluate the influence of pH, PEG molecular weight, tie
      line length, phase volume ratio, and lysate load. To build the mathematical model
      and minimize the number of experiments for the design parameters, response
      surface methodology (RMS) with an orthogonal rotatable central composite design
      was defined based on the conditions found for the highest purification by
      preliminary tests. The adequacy of the calculated models for the plasmid recovery
      and remaining RNA were confirmed by means of variance analysis and additional
      experiments. Analysis of contours of constant response as a function of pH, PEG
      molecular weight, tie line length, and cell lysate load for three different phase
      volume ratios revealed different effects of these five factors on the studied
      parameters. Plasmid recovery of 99% was predicted for a system with PEG 400, pH
      6.9, tie line length of 38.7%, phase volume ratio of 1.5, and lysate load of 10%
      (v/v). Under these conditions the predicted RNA removal was 68%.

PMID- 16615145
TI  - Unexpected improvement in stability and utility of cytochrome c by solution in
      biocompatible ionic liquids.
AB  - Proteins generally are only stable in vitro for short periods of time. This
      results in challenges during isolation and purification of recombinant proteins
      and reduces the shelf life of protein-based pharmaceuticals. Here we show that
      certain novel, biocompatible ionic liquids provide a stabilizing solvent for
      proteins, for example, cytochrome c, such that structure and activity are
      maintained even after 6 months of storage at room temperature. Normally, this
      protein would be rendered inactive after only 1 week in buffered aqueous
      solution. The effect of the ionic liquid solvent appears to be related to
      protection against hydrolysis.

PMID- 16615146
TI  - Kinetics of lactose fermentation using a recombinant Saccharomyces cerevisiae
      strain.
AB  - This work presents a multi-route, non-structural kinetic model for interpretation
      of ethanol fermentation of lactose using a recombinant flocculent Saccharomyces
      cerevisiae strain expressing both the LAC4 (coding for beta-galactosidase) and
      LAC12 (coding for lactose permease) genes of Kluyveromyces lactis. In this model,
      the values of different metabolic pathways are calculated applying a modified
      Monod equation rate in which the growth rate is proportional to the concentration
      of a key enzyme controlling the single metabolic pathway. In this study, three
      main metabolic routes for S. cerevisiae are considered: oxidation of lactose,
      reduction of lactose (producing ethanol), and oxidation of ethanol. The main
      bioprocess variables determined experimentally were lactose, ethanol, biomass,
      and dissolved oxygen concentrations. Parameters of the proposed kinetic model
      were established by fitting the experimental data obtained in a small lab-scale
      fermentor with the initial lactose concentrations ranging from 5 g/dm3 to 50
      g/dm3. A very good agreement between experimental data and simulated profiles of
      the main variables (lactose, ethanol, biomass, and dissolved oxygen
      concentrations) was achieved.

PMID- 16615147
TI  - Re: the risk of developing metastatic disease in colorectal cancer is related to
      CD105-positive vessel count, by Romani AA, Borghetti AF, Del Rio P, et al.

PMID- 16615148
TI  - Lymph node counts, rates of positive lymph nodes, and patient survival for colon
      cancer surgery in Ontario, Canada: a population-based study.
AB  - BACKGROUND AND OBJECTIVES: This study assessed lymph node counts, lymph node
      status (positive or negative), and survival among patients undergoing colon
      cancer surgery in Ontario, Canada. METHODS: We obtained data from the Ontario
      Cancer Registry on 960 patients who underwent a major colon cancer resection in
      years 1991-1993. Patients and hospitals were ranked by lymph node count to
      correlate lymph node counts and lymph node status. For node-negative patients we
      assessed the influence of patient, hospital, and tumor factors on lymph node
      counts and survival. RESULTS: The rate of node-positive patients was similar
      among the lymph node count groups. For example, the odds ratio of a patient being
      node positive if the lymph node count was 10-36 versus 1-3 was 1.0 (CI 0.6-1.6, P
      = 0.42). Among node-negative patients, survival was improved for patients with a
      high (10-36) versus low (1-3) lymph node count (HR 0.6, CI 0.4-1.0, P = 0.03). No
      patient, hospital, or tumor factors predicted both a higher lymph node count and
      improved survival. CONCLUSIONS: In this population-based study of patients
      undergoing colon cancer surgery, higher lymph node counts did not correlate with
      increased rates of node-positive status.

PMID- 16615149
TI  - Primary and recurrent retroperitoneal soft tissue sarcoma: prognostic factors
      affecting survival.
AB  - BACKGROUND AND OBJECTIVES: To analyze treatment and survival in 34 patients (28
      resected) with primary or recurrent retroperitoneal sarcoma (RPS). METHODS:
      Between July 1994 and January 2001, 34 patients (15M, 19F; mean age: 56 years,
      range: 25-77) were evaluated. Complete resection was defined as removal of gross
      tumor with histologically confirmed clear resection margins. RESULTS: Twenty
      eight out of 34 patients (82%) (15 were affected by primary RPS, and 13 by
      recurrent RPS), underwent surgical exploration. Twenty-three patients had a
      grossly and microscopically complete resection, (3 having a grossly incomplete
      resection and 2 patients with a grossly complete resection having histologically
      involved resection margins). Twenty-one out of 28 patients (75%) underwent
      removal of contiguous intra-abdominal organs. Preoperative mortality was nil, and
      morbidity occurred in six cases only (21%). High tumor grade results a
      significant variable for a worse survival in all 28 patients (100% 5 years
      survival for low grade vs. 0% for high grade; P = 0.0004). Amongst completely
      resected patients, only histologic grade and peroperative blood transfusions
      affected disease-free survival (P = 0.04 and P = 0.05, respectively).
      CONCLUSIONS: An aggressive surgical approach in both primary and recurrent RPS is
      associated with long-term survival.

PMID- 16615150
TI  - A prospective trial for avoiding cervical lymph node dissection for thoracic
      esophageal cancers, based on intra-operative genetic diagnosis of micrometastasis
      in recurrent laryngeal nerve chain nodes.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the usefulness
      of intra-operative genetic diagnosis of RN node micrometastasis in the decision
      making of 3FL for thoracic esophageal cancers. METHODS: Eighty-nine patients with
      middle and lower thoracic esophageal cancer were enrolled in a prospective study,
      in which 3FL was performed when RN node metastasis was revealed by intra
      operative histological examination and/or genetic analysis using real-time RT-PCR
      assay. For other cases, 2FL was performed. RESULTS: Of the 89 patients, 3FL was
      performed for 33 patients and 2FL for 56 patients. In the 3FL group, RN node
      metastasis was both histologically and genetically positive in 19 patients,
      histologically negative and genetically positive in 11, and histologically
      positive and genetically negative in 3, with cervical node metastasis being
      detected in 7, 3, and 0 patients, respectively. In the 2FL group, only one
      patient had cervical node recurrence during the follow-up period. The post
      operative survival in this study was equivalent to that of the historical
      controls (3-year survival rates 63.9% vs. 52.3%, P = 0.1513) of 66 3FL patients
      when 3FL was the first choice for thoracic esophageal cancers. CONCLUSIONS: Intra
      operative histological and genetic diagnosis of RN node metastasis may help avoid
      unnecessary cervical node resection. A Phase III trial should be done.

PMID- 16615151
TI  - Does postoperative chemotherapy have a survival benefit for patients with
      pancreatic cancer?
AB  - In our study, we investigated whether postoperative chemotherapy improved
      survival in patients with invasive ductal carcinoma of the pancreas. Between 1987
      and 2004, 111 patients underwent pancreatic resection against invasive ductal
      carcinoma of the pancreas in Wakayama Medical University Hospital. Median
      survival time (MST) was 19.4 months, 8.6 months, and 7.2 months, in JPS Stage III
      (UICC Stage IIA and IIB), JPS Stage IVa (UICC Stage IIA and IIB), and JPS Stage
      IVb (UICC Stage IV), respectively (P < 0.01). The MST of the chemotherapy group
      was 12 months, and the MST of the non-chemotherapy group was 8.4 months (P <
      0.05). Moreover, in JPS Stage IV (UICC Stage IIA, IIB, III, and IV) highly
      advanced pancreatic cancer, the MST of the chemotherapy group was 10.9 months,
      and the MST of the group without chemotherapy was 6.6 months (P < 0.01). Since
      pancreatic cancer is characterized by an aggressive tumor with a high recurrent
      rate, postoperative chemotherapy is effective for an improvement of survival.

PMID- 16615152
TI  - Matrilsin expression is a useful marker of submucosal invasion and lymph node
      metastasis in early stage signet ring cell carcinoma of the stomach.
AB  - BACKGROUND: Matrilysin (MMP-7) is considered to play an important role in tumor
      progression and metastasis. The aim of this study was to examine the MMP-7
      expression of early-stage undifferentiated gastric carcinoma, and to investigate
      differences between gastric signet ring cell (SIG) and other undifferentiated
      carcinomas (non-SIG). METHODS: Immunohistochemical staining of MMP-7 was
      performed using specimens from 150 patients with early-stage gastric
      undifferentiated carcinomas (76 SIG, 74 non-SIG). RESULTS: SIG had a larger
      proportion of mucosal-confined carcinoma and a lower rate of lymphatic invasion
      than non-SIG (P < 0.05). The incidence of the positive expression of MMP-7 in
      submucosal SIG was significantly higher than that of mucosal SIG (P < 0.01). In
      contrast, MMP-7 expression was frequently found in mucosal non-SIG, suggesting an
      apparent difference in the invasiveness between mucosal SIG and non-SIG. The
      larger the size of the mucosal SIG, the more frequently MMP-7 positive expression
      was demonstrated (P < 0.05). There was a significant correlation between MMP-7
      positive expression and lymph node metastasis of early SIG (P < 0.05).
      CONCLUSION: Early SIG revealed less invasiveness than non-SIG in terms of
      clinicopathologic features and MMP-7 expression. Preoperative estimation of the
      MMP-7 expression might be useful as a predictor of submucosal invasion and lymph
      node metastasis in early SIG.

PMID- 16615153
TI  - Metastasis-associated protein S100A4--a potential prognostic marker for
      colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Expression of S100A4, a small calcium-binding protein,
      in breast, oesophagus and gall bladder cancers is shown to be associated with
      adverse clinical outcome. We retrospectively examined the correlation of S100A4
      expression and outcome in patients with colorectal cancer. METHODS: Tissue
      sections from 54 patients with Dukes B, C and D cancers operated on between 1995
      and 1998 were stained with anti-S100A4 antibody. The S100A4 expression profile
      was correlated to the clinico-pathological details. RESULTS: There were 31 males
      and 23 females (mean age 65.94 years +/- 12.29). Dukes stage, >4 positive lymph
      node status and S100A4 expression were significantly associated with poorer
      survival. The 3 years survival of patients whose tumour stained positive for
      S100A4 was 62.85% compared to 93.75% for those stained negative (P < 0.012). In
      patients with <4 involved nodes, S100A4 expression led to poorer survival (57
      months vs. 74 months; P < 0.0052). Within a particular Dukes stage, S100A4
      expression was associated with poorer outcome. The 5 years survival of Dukes B
      patients whose tumour stained negative for S100A4 was 92% compared to 54.6% for
      those with positive tumours. CONCLUSION: Our results suggest that S100A4
      expression is associated with adverse clinical outcome. Inclusion of S100A4
      expression status may enhance our accuracy to prognosticate in patients with
      colorectal cancer.

PMID- 16615154
TI  - The changes of estrogen receptor-beta variants expression in breast
      carcinogenesis: Decrease of estrogen receptor-beta2 expression is the key event
      in breast cancer development.
AB  - BACKGROUND AND OBJECTIVES: Although more than five variant forms of estrogen
      receptor-beta (ERbeta) have been identified, their role has not been identified.
      This study was carried out to investigate the changes of ERbeta variants in
      breast cancer development. METHODS: Using reverse transcription polymerase chain
      reaction (RT-PCR) and triple primer PCR (TP-PCR), the expression levels of ERbeta
      variants mRNA were measured in 66 paired normal and cancer tissues. The relative
      expression level of ERbeta variants were compared between normal and cancer
      tissues, and also compared according to various clinicopathological parameters.
      RESULTS: Among ERbeta variants, ERbeta2 and ERbeta5 consist of the major
      proportion of ERbeta expression both in normal and cancer tissues. The ERbeta and
      ERbeta2 expression levels decreased significantly in the cancers compared with
      corresponding normal tissues, particularly in ERalpha-expressing cancers.
      However, ERbeta5 expression level increased significantly in the cancers,
      especially in those of postmenopausal patients. The relative increase of ERbeta5
      expression in cancer tissues was associated with favorable differentiation.
      CONCLUSIONS: Decrease of ERbeta2 is thought to be the key reason for the decrease
      in ERbeta expression in cancer tissues, and it is particularly associated with
      the development of ERalpha-expressing breast cancer.

PMID- 16615155
TI  - Advantage of pancreaticogastrostomy in detecting recurrent intraductal papillary
      mucinous carcinoma in the remnant pancreas: a case of successful re-resection
      after pancreaticoduodenectomy.
AB  - Recently there has been an increase in the number of case reports detailing the
      recurrence of cancer in the pancreatic remnants following surgical resection of
      intraductal papillary mucinous carcinoma (IPMC) of the pancreas. A case is
      presented here to indicate the advantage of pancreaticogastrostomy (PG) in terms
      of postoperative follow-up after pancreaticoduodenectomy (PD) for IPMC. A 68-year
      old man underwent PD for IPMC of the pancreatic head, and the cut margin of the
      pancreatic duct was diagnosed as having no cancer but moderately dysplastic
      epithelium by an intraoperative frozen section of histology. Thus, we decided to
      proceed with a PG rather than pancreaticojejunostomy (PJ) in order to facilitate
      easier postoperative examinations. Eight years and 6 months later, during a
      routine follow-up examination, duct dilation of the remnant pancreas was detected
      by magnetic resonance imaging (MRI). Upon examination by endoscopic gastroscopy,
      the anastomotic site was found to be covered with a large amount of mucin from
      which we easily obtained both cytologic and biopsied specimens, which
      subsequently proved positive for cancer. In line with our diagnosis of recurrent
      IPMC, the patient underwent a second surgery (resection of the remnant pancreas,
      total pancreatectomy) and postoperative histology confirmed that indeed the
      patient had experienced recurrent IPMC with no nodal involvement or invasion
      beyond the pancreatic confines. Based on this experience, we decided to recommend
      PG for all patients deemed to be at high risk for the recurrence of cancer in the
      pancreatic remnants following PD for IPMC of the pancreatic head.

PMID- 16615156
TI  - Re: a prospective trial for avoiding cervical lymph node dissection for thoracic
      esophageal cancers, based on intra-operative genetic diagnosis of micrometastasis
      in recurrent laryngeal nerve chain nodes, by Miyata H, Yano M, Doki Y, et al.

PMID- 16615157
TI  - The risk of developing metastatic disease in colorectal cancer is related to
      CD105-positive vessel count.
AB  - BACKGROUND AND OBJECTIVES: Angiogenesis is a complex multistep process that
      involves extracellular matrix remodeling, migration and proliferation of
      endothelial cells, and morphogenesis of microvessels. CD105 (endoglin), a co
      receptor of the TGF-beta superfamily, was proposed as a marker of
      neovascularization in solid malignancies. The aim of this study was to evaluate
      retrospectively the effect of CD105-assessed angiogenesis on the risk of
      developing metastatic disease in colorectal cancer (CRC). METHODS: One hundred
      and twenty-five paraffin-embedded samples were analyzed by immunohistochemical
      methods using a CD105 monoclonal antibody. The median follow-up was 70.8 months.
      Survivals were calculated from actuarial estimates, and logistic regression
      predicted the risk of developing metastatic disease. RESULTS: The CD105-vessel
      count was strongly correlated with the occurrence of metastatic disease. The
      median CD105-positive vessels in patients with and without metastatic disease
      were 24.7 and 13.2 vessels/mm(2), respectively (P < 0.001). For each one
      microvessel increase in the vessels count per 400x field, there was a 1.42-fold
      increase in the risk of metastatic disease (P < 0.001). CONCLUSIONS: The
      assessment of tumor angiogenesis with anti-CD105 was not sufficient for its use
      as a surrogate end point for survival because of the amount of survival
      variability explained was only 8% in absence of metastatic disease. In contrast,
      multivariate logistic regression analysis revealed that CD105-vessels count can
      identify patients at high risk of metastatic disease.

PMID- 16615158
TI  - Elective lateral neck dissection for laryngeal cancer in the clinically negative
      neck.
AB  - BACKGROUND: Despite the introduction of modern imaging techniques, it is still
      difficult to detect microscopic disease in neck nodes. The purpose of this study
      is to evaluate the efficacy of the lateral neck dissection (LND) for elective
      treatment of the clinically node negative neck (cN0) in laryngeal squamous cell
      carcinoma (SCC). METHODS: The clinical records of 110 cN0 patients with laryngeal
      SCC treated in this hospital from January 1997 to December 2002 were reviewed
      retrospectively. RESULTS: One hundred ten patients received 145 elective LND.
      Occult metastasis was detected in 22 (20.0%) of this group of patients. The
      distribution of the 37 positive nodes was as follows: Level II 56.8%; Level III
      37.8%; Level IV 5.4%. The 3-year neck recurrence rate estimated by the Kaplan
      Meier approach for all cN0 patients (n = 110) was 5.4% [95% CI: 0.0%; 12.5%]. No
      significant difference in 3-year lymph node recurrence was found between node
      negative and node positive groups, between supraglottis and glottis groups, or
      between surgery alone and combined therapy groups. CONCLUSION: The lateral neck
      dissection is effective in elective treatment of the neck in patients with
      laryngeal carcinoma.

PMID- 16615159
TI  - A reappraisal of surgical management for squamous cell carcinoma in the
      pharyngoesophageal junction.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) in the pharyngoesophageal junction
      (PEJ) with concomitant involvement of both the hypopharynx and cervical esophagus
      occurs rarely and poses a challenge in treatment. Data regarding the long-term
      result of aggressive surgical management was lacking. METHODS: Forty-one
      consecutive patients were treated with total pharyngolaryngo-esophagectomy (PLE)
      and reconstruction between 1984 and 2002. The clinicopathological parameters and
      prognostic data were analyzed. RESULTS: The surgery carried a postoperative
      mortality rate of 9.8%. The overall median survival was 18.5 months, with a 31.5%
      5-year survival rate. By multivariate analysis, patients with major tumor
      localization in the hypopharynx had significantly favorable prognosis (median
      survivals for hypopharyngeal versus esophageal localization, 37.2 versus 7.1
      months, P = 0.043). The administration of adjuvant radiotherapy and tumor size
      less than 5 cm also contributed to a better outcome (P = 0.001 and P = 0.037,
      respectively). CONCLUSIONS: An aggressive surgical approach with total PLE in
      conjunction with adjuvant radiotherapy represents a feasible option for treatment
      of advanced SCC simultaneously involving the hypopharynx and cervical esophagus,
      given the major tumor localization in the hypopharynx. On the other hand, radical
      surgery for those with major esophageal localization or with tumor size larger
      than 5 cm yielded ominous results and warrants further justification.

PMID- 16615160
TI  - Three-dimensional biofilm model with individual cells and continuum EPS matrix.
AB  - An innovative type of biofilm model is derived by combining an individual
      description of microbial particles with a continuum representation of the biofilm
      matrix. This hybrid model retains the advantages of each approach, while
      providing a more realistic description of the temporal development of biofilm
      structure in two or three spatial dimensions. The general model derivation takes
      into account any possible number of soluble components. These are substrates and
      metabolic products, which diffuse and react in the biofilm within individual
      microbial cells. The cells grow, divide, and produce extracellular polymeric
      substances (EPS) in a multispecies model setting. The EPS matrix is described by
      a continuum representation as incompressible viscous fluid, which can expand and
      retract due to generation and consumption processes. The cells move due to a
      pushing mechanism between cells in colonies and by an advective mechanism
      supported by the EPS dynamics. Detachment of both cells and EPS follows a
      continuum approach, whereas cells attach in discrete events. Two case studies are
      presented for model illustration. Biofilm consolidation is explained by shrinking
      due to EPS and cell degradation processes. This mechanism describes formation of
      a denser layer of cells in the biofilm depth and occurrence of an irregularly
      shaped biofilm surface under nutrient limiting conditions. Micro-colony formation
      is investigated by growth of autotrophic microbial colonies in an EPS matrix
      produced by heterotrophic cells. Size and shape of colonies of ammonia and
      nitrite-oxidizing bacteria (NOB) are comparatively studied in a standard biofilm
      and in biofilms aerated from a membrane side.

PMID- 16615161
TI  - Biological hydrogen production in a UASB reactor with granules. II: Reactor
      performance in 3-year operation.
AB  - The experiment was conducted to evaluate the performance of an upflow anaerobic
      sludge blanket (UASB) with granules for H(2) production from a sucrose-rich
      synthetic wastewater at various substrate concentrations (5.33-28.07 g-COD/L) and
      hydraulic retention times (HRTs) (3-30 h) for over 3 years. The kinetics of H(2)
      production was evaluated, and the sludge yield and endogenous decay coefficient
      of the H(2)-producing granules were estimated to be 0.334 g-VSS/g-COD and
      0.004/h, respectively. Based on Gibbs free energy calculations, the formation
      thermodynamics of caproate, an important aqueous product, were analyzed.
      Experimental results show that the H(2) partial pressure in biogas decreased with
      increasing substrate concentration, but was not sensitive to the variation of HRT
      in a range of 6-22 h. The H(2) production rate increased with increasing
      substrate concentration, but decreased with increasing HRT. The H(2) yield was in
      the range of 0.49-1.44 mol-H(2)/mol-glucose. Acetate, butyrate, caporate, and
      ethanol were the main aqueous products in the reactor, and their concentrations
      were dependent on both substrate concentration and HRT. An elevated substrate
      concentration resulted in a shift of fermentation from butyrate- to caporate-type
      in the reactor and the formation of caproate was dependent on the H(2) partial
      pressure. The 3-year experimental results demonstrate that H(2) could be produced
      continuously and stably from the acidogenic-granule-based UASB reactor.

PMID- 16615163
TI  - Interactions between mycoplasma lipid-associated membrane proteins and the host
      cells.
AB  - Mycoplamas are a group of wall-less prokaryotes widely distributed in nature,
      some of which are pathogenic for humans and animals. There are many lipoproteins
      anchored on the outer face of the plasma membrane, called lipid-associated
      membrane proteins (LAMPs). LAMPs are highly antigenic and could undergo phase and
      size variation, and are recognized by the innate immune system through Toll-like
      receptors (TLR) 2 and 6. LAMPs can modulate the immune system, and could induce
      immune cells apoptosis or death. In addition, they may associate with malignant
      transformation of host cells and are also considered to be cofactors in the
      progression of AIDS.

PMID- 16615162
TI  - Organ preconditioning: the past, current status, and related lung studies.
AB  - Preconditioning (PC) has emerged as a powerful method for experimentally and
      clinically attenuating various types of organ injuries. In this paper related
      clinical and basic research issues on organ preconditioning issues were
      systemically reviewed. Since lung injuries, including ischemia-reperfusion and
      others, play important roles in many clinical results, including thromboembolism,
      trauma, thermal injury, hypovolemic and endotoxin shock, reimplantation response
      after organ transplantation, and many respiratory diseases in critical care. It
      is of interest to uncover methods, including the PCs, to protect the lung from
      the above injuries. However, related studies on pulmonary PC are relatively rare
      and still being developed, so we will review previous literature on experimental
      and clinical studies on pulmonary PC in the following paragraphs.

PMID- 16615164
TI  - Tissue-engineered graft constructed by self-derived cells and heterogeneous
      acellular matrix.
AB  - BACKGROUND: Endothelial and smooth muscle cells were used as seeding cells and
      heterogeneous acellularized matrix was used as scaffold to construct the tissue
      engineered graft. METHODS: A 2 weeks piglet was selected as a donor of seeding
      cells. Two-centimetre length of common carotid artery was dissected. Endothelial
      cells and smooth muscle cells were harvested by trypsin and collagenase digestion
      respectively. The isolated cells were cultured and expanded using routine cell
      culture technique. An adult sheep was used as a donor of acellularized matrix.
      The thoracic aorta was harvested and processed by a multi-step decellularizing
      technique to remove the original cells and preserve the elastic and collagen
      fibers. The cultured smooth muscle cells and endothelial cells were then seeded
      to the acellularized matrix and incubated in vitro for another 2 weeks. The cell
      seeded graft was then transplanted to the cell-donated piglet to substitute part
      of the native pulmonary artery. RESULTS: The cultured cells from piglet were
      characterized as endothelial cells by the presence of specific antigens vWF and
      CD31, and smooth muscle cells by the presence of specific antigen alpha-actin on
      the cell surface respectively with immunohistochemical technique. After
      decellularizing processing for the thoracic aorta from sheep, all the cellular
      components were extracted and elastic and collagen fibers kept their original
      morphology and structure. The maximal load of acellular matrix was decreased and
      20% lower than that of untreated thoracic aorta, but the maximal tensions between
      them were not different statistically and they had similar load-tension curves.
      Three months after transplantation, the animal was sacrificed and the graft was
      removed for observation. The results showed that the inner surfaces of the graft
      were smooth, without thrombosis and calcification. Under microscopy, a great
      number of growing cells could be seen and elastic and collagen fibers were
      abundant. CONCLUSION: Cultured self-derived endothelial and smooth muscle cells
      could be used as seeding cells and heterogeneous acellularized matrix could be
      used as scaffold in constructing tissue-engineered graft.

PMID- 16615165
TI  - Inter- and intra-hemispheric EEG coherence in patients with mild cognitive
      impairment at rest and during working memory task.
AB  - OBJECTIVE: To assess functional relationship by calculating inter- and intra
      hemispheric electroencephalography (EEG) coherence at rest and during a working
      memory task of patients with mild cognitive impairment (MCI). METHODS: The sample
      consisted of 69 subjects: 35 patients (n=17 males, n=18 females; 52-71 years old)
      and 34 normal controls (n=17 males, n=17 females; 51~63 years old). Mini-mental
      state examination (MMSE) of two groups revealed that the scores of MCI patients
      did not differ significantly from those of normal controls (P>0.05). In EEG
      recording, subjects were performed at rest and during working memory task. EEG
      signals from F3-F4, C3-C4, P3-P4, T5-T6 and O1-O2 electrode pairs are resulted
      from the inter-hemispheric action, and EEG signals from F3-C3, F4-C4, C3-P3, C4
      P4, P3-O1, P4-O2, T5-C3, T6-C4, T5-P3 and T6-P4 electrode pairs are resulted from
      the intra-hemispheric action for delta (1.0-3.5 Hz), theta (4.0-7.5 Hz), alpha-1
      (8.0-10.0 Hz), alpha-2 (10.5-13.0 Hz), beta-1 (13.5-18.0 Hz) and beta-2 (18.5
      30.0 Hz) frequency bands. The influence of inter- and intra-hemispheric coherence
      on EEG activity with eyes closed was examined using fast Fourier transformation
      from the 16 sampled channels. RESULTS: During working memory tasks, the inter-
      and intra-hemispheric EEG coherences in all bands were significantly higher in
      the MCI group in comparison with those in the control group (P<0.05). However,
      there was no significant difference in inter- and intra-hemispheric EEG
      coherences between two groups at rest. CONCLUSION: Experimental results comprise
      evidence that MCI patients have higher degree of functional connectivity between
      hemispheres and in hemispheres during working condition. It suggests that MCI may
      be associated with compensatory processes during working memory tasks between
      hemispheres and in hemispheres. Moreover, failure of normal cortical connections
      may exist in MCI patients.

PMID- 16615166
TI  - SVM for density estimation and application to medical image segmentation.
AB  - A method of medical image segmentation based on support vector machine (SVM) for
      density estimation is presented. We used this estimator to construct a prior
      model of the image intensity and curvature profile of the structure from training
      images. When segmenting a novel image similar to the training images, the
      technique of narrow level set method is used. The higher dimensional surface
      evolution metric is defined by the prior model instead of by energy minimization
      function. This method offers several advantages. First, SVM for density
      estimation is consistent and its solution is sparse. Second, compared to the
      traditional level set methods, this method incorporates shape information on the
      object to be segmented into the segmentation process. Segmentation results are
      demonstrated on synthetic images, MR images and ultrasonic images.

PMID- 16615167
TI  - Functional analysis of helicase and three tandem HRDC domains of RecQ in
      Deinococcus radiodurans.
AB  - RecQ is a highly conserved helicase necessary for maintaining genome stability in
      all organisms. Genome comparison showed that a homologue of RecQ in Deinococcus
      radiodurans designated as DR1289 is a member of RecQ family with unusual domain
      arrangement: a helicase domain, an RecQ C-terminal domain, and surprisingly three
      HRDC domain repeats, whose function, however, remains obscure currently. Using an
      insertion deletion, we discovered that the DRRecQ mutation causes an increase in
      gamma radiation, hydroxyurea and mitomycine C and UV sensitivity. Using the
      shuttle plasmid pRADK, we complemented various domains of the D. radiodurans RecQ
      (DRRecQ) to the mutant in vivo. Results suggested that both the helicase and
      helicase-and-RNase-D-C-terminal (HRDC) domains are essential for complementing
      several phenotypes. The complementation and biochemical function of DRRecQ
      variants with different domains truncated in vitro suggested that both the
      helicase and three HRDC domains are necessary for RecQ functions in D.
      radiodurans, while three HRDC domains have a synergistic effect on the whole
      function. Our finding leads to the hypothesis that the RecF recombination pathway
      is likely a primary path of double strand break repair in this well-known
      radioresistant organism.

PMID- 16615168
TI  - Roots of pioneer trees in the lower sub-tropical area of Dinghushan, Guangdong,
      China.
AB  - Representative pioneer tree root systems in the subtropical area of South China
      were examined with regard to their structure, underground stratification and
      biomass distribution. Excavation of skeleton roots and observation of fine roots
      of seven species including the Euphorbiaceae, Theaceae, Melastomataceae,
      Lauraceae and Fagaceae families was carried out. The results showed that: (1)
      Pioneer tree roots in the first stage of natural succession were of two types,
      one characterized by taproot system with bulky plagiotropic branches; the other
      characterized by flat root system with several tabular roots. The late
      mesophilous tree roots were characterized by one obvious taproot and tactic
      braches roots up and down. Shrub species roots were characterized by heart
      fibrous root type featured both by horizontally and transversally growing
      branches. Root shapes varied in different dominant species at different stages of
      succession. (2) Roots of the different species varied in the external features
      color, periderm and structure of freshly cut slash. (3) In a set of successional
      stages the biomass of tree roots increased linearly with the age of growth.
      During monsoon, the total root biomass amounted to 115.70 t/ha in the evergreen
      broad-leaved forest; 50.61 t/ha in needle and broad-leaved mixed forest dominated
      by coniferous forest; and 64.20 t/ha in broad-and needle-leaved mixed forest
      dominated by broad-leaved heliophytes, and are comparable to the underground
      biomass observed in similar tropical forests. This is the first report about
      roots characteristics of forest in the lower sub-tropical area of Dinghushan,
      Guangdong, China.

PMID- 16615169
TI  - Genotypic and environmental variation in barley limit dextrinase activity and its
      relation to malt quality.
AB  - Variation in the limit dextrinase activity of barley malt, and the relationships
      between limit dextrinase activity and malt quality parameters were investigated
      using eight cultivars grown at seven diverse locations in China for two
      successive years. Limit dextrinase activity varied with genotype and location,
      with the levels ranging from 0.245 U/g to 0.980 U/g. The results showed that the
      variation in limit dextrinase activity was more attributable to the environment
      (location and year) than to the genotype. The response of limit dextrinase
      activity to the environment differed markedly among cultivars, and was reflected
      by large difference in coefficient of variation of cultivars across diverse
      locations. Regression analysis showed that limit dextrinase activity was
      negatively correlated with malt viscosity (r=-0.52, P<0.01), positively
      correlated with Kolbach index (r=0.38, P<0.01) and malt extract (r=0.30, P<0.05),
      but had no significant correlation with malt protein content and diastatic power.

PMID- 16615170
TI  - A convenient and stereoselective synthesis of (Z)-allyl selenides via Sm/TMSCl
      system-promoted coupling of Baylis-Hillman adducts with diselenides.
AB  - A simple and convenient procedure for stereoselective synthesis of (Z)-allyl
      selenides has been developed by a one-pot reaction of diselenides with Baylis
      Hillman adducts in the presence of samarium metal-trimethylsilyl chloride under
      mild conditions. Presumably, the diselenides are cleaved by Sm/TMSCl system to
      form selenide anions, which then undergo S(N)2' substitution of Baylis-Hillman
      adducts to produce the (Z)-allyl selenides.

PMID- 16615171
TI  - Combined treatment of landfill leachate with fecal supernatant in sequencing
      batch reactor.
AB  - A laboratory-scale sequencing batch reactor (SBR) is used to treat landfill
      leachate containing high concentration of ammonium nitrogen with municipal fecal
      supernatant. The SBR system is operated in the following sequential phases: fill
      period, anoxic period, aeration period, settling period, decant and idle period.
      The results indicated that the average removal efficiencies of COD, BOD(5),
      TN,NH(4)(+)-N were 93.76%, 98.28%, 84.74% and 99.21%, respectively. The average
      sludge removal loading rates of COD, BOD(5), TN and NH(4)(+)-N were 0.24 kg/(kg
      SS.d), 0.08 kg/(kg SS.d), 0.04 kg/(kg SS.d) and 0.036 kg/(kg SS.d), respectively.
      Highly effective simultaneous nitrification and denitrification was achieved in
      the SBR system. The ratio of nitrification and denitrification was 99% and 84%,
      respectively. There was partial NO(2)(-) denitrification in the system.

PMID- 16615172
TI  - Hg(0) absorption in potassium persulfate solution.
AB  - The aqueous phase oxidation of gaseous elemental mercury (Hg(0)) by potassium
      persulfate (KPS) catalyzed by Ag(+) was investigated using a glass bubble column
      reactor. Concentration of gaseous mercury and potassium persulfate were measured
      by cold vapor atom absorption (CVAA) and ion chromatograph (IC), respectively.
      The effects of pH value, concentration of potassium persulfate and silver nitrate
      (SN), temperature, Hg(0) concentration in the reactor inlet and tertiary butanol
      (TBA), free radical scavenger, on the removal efficiency of Hg(0) were studied.
      The results showed that the removal efficiency of Hg(0) increased with increasing
      concentration of potassium persulfate and silver nitrate, while temperature and
      TBA were negatively effective. Furthermore, the removal efficiency of Hg(0) was
      much better in neutral solution than in both acidic and alkaline solution. But
      the influence of pH was almost eliminated by adding AgNO(3). High Hg(0)
      concentration has positive effect. The possible reaction mechanism of gaseous
      mercury was also discussed.

PMID- 16615173
TI  - Biological monitoring in occupational and environmental toxicology. Proceedings
      of the 6th International Symposium on Biological Monitoring. September 6-8, 2004.
      Heidelberg, Germany.

PMID- 16615174
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 16615175
TI  - The hidden and potent effects of television advertising.

PMID- 16615176
TI  - Dopant-induced nanoscale electronic inhomogeneities in Ca(2-x)Sr(x)RuO4.
AB  - Ca(2-x)Sr(x)RuO4 single crystals with 0.1 < or = x < or = 2.0 have been studied
      systematically using scanning tunneling microscopy (STM) and spectroscopy, low
      energy electron diffraction, and angle resolved photoelectron spectroscopy
      (ARPES). In contrast with the well-ordered lattice structure, the local density
      of states at the surface clearly shows a strong doping dependent nanoscale
      electronic inhomogeneity, regardless of the fact of isovalent substitution.
      Remarkably, the surface electronic roughness measured by STM and the inverse
      spectral weight of quasiparticle states determined by ARPES are found to vary
      with x in the same manner as the bulk in-plane residual resistivity, following
      the Nordheim rule. For the first time, the surface measurements--especially those
      with STM--are shown to be in good agreement with the bulk transport results, all
      clearly indicating a doping-induced electronic disorder in the system.

PMID- 16615177
TI  - A structural account of phonological paraphasias.
AB  - The aim of this study is to develop a partial theory of phonological paraphasias
      which has some cross-syndrome and cross-linguistic validity. It is based on the
      distinction between content and structural units and emphasizes the role of the
      latter. The notion of structure holds the key to an understanding of the
      differences among the following three types of data: slips of the tongue, slips
      of the pen (defined as errors committed by healthy, competent adults), and
      paraphasias. A comparison of these three data types reveals that slips of the pen
      and paraphasias display striking similarities whereas slips of the tongue stand
      apart. This pattern emerges very clearly in an analysis of nine empirical effects
      all of which are found to be of a structural nature. On the basis of these
      results, it is argued that both the written output of normals and the oral output
      of aphasics are generated under a reduced structural representation (i.e., weak
      activation of structural nodes). However, the reasons for the diminished
      sensitivity to structure are not the same in the two modalities. While the
      impoverished structural representation is a likely consequence of the relatively
      slow production rate in writing, it may stem from an impaired transmission of
      activation among structural nodes in aphasia. By contrast, the normal speaking
      process occurs under the sway of a full-fledged structural representation. Hence,
      slips of the tongue are highly sensitive to structural effects.

PMID- 16615179
TI  - Abstracts of the the American Society for Neurochemistry 37th Annual Meeting,
      Portland, Oregon, USA, 11-15 March 2006.

PMID- 16615178
TI  - Dietary nucleotides and human immune cells. II. Modulation of PBMC growth and
      cytokine secretion.
AB  - OBJECTIVE: The immune system is dependent on purines and pyrimidines as building
      blocks for DNA and RNA synthesis to enable rapid cell proliferation and protein
      synthesis. Emerging evidence suggests that dietary nucleotides optimize immune
      function. We investigated whether growth and function of human immune cells were
      affected by an exogenous source of nucleotides during specific antigen challenge.
      METHODS: Peripheral blood mononuclear cells from healthy individuals (n = 10)
      were stimulated with influenza virus antigen and either DNA sodium from fish soft
      roe (DNA), RNA from bakers yeast (Saccharomyces cerevisiae) (RNA), 2'
      deoxyadenosine 5'-monophosphate sodium (dAMP), 2' deoxycytidine 5'-monophosphate
      sodium (dCMP), 2' deoxyguanosine 5'-monophosphate sodium (dGMP), 2' deoxyuridine
      5'-monophosphate sodium (dUMP) or thymidine sodium (TMP). Growth effects were
      ascertained by measuring the amount of tritium-labeled thymidine, incorporated
      into cell DNA. Cell function was measured by detection of IFN-gamma, TNF-alpha
      and IL-10 production. RESULTS: Specific nucleotide derivatives alone did not
      affect the growth of healthy peripheral blood mononuclear cells. However, the
      nucleotide derivatives influenced immune cell growth and cytokine secretion when
      cocultured with specific antigen. DNA, RNA, dAMP, dCMP and dUMP increased
      influenza virus antigen induced immune cell proliferation. In contrast dGMP and
      TMP inhibited the antigen-induced growth response. RNA and dAMP cocultured with
      virus antigen significantly increased peripheral blood mononuclear cell secretion
      of IFN-gamma, IL-10 and TNF-alpha. DNA increased virus antigen-induced immune
      cell secretion of IFN-gamma only, whereas dUMP significantly increased secretion
      of IL-10 only. dGMP completely inhibited virus-triggered IFN-gamma secretion,
      whereas TMP did not change the virus induced secretion pattern of measured
      cytokines. CONCLUSION: Nucleotide derivatives affect growth and function of
      specific virus antigen-stimulated human immune cells in vitro.

PMID- 16615180
TI  - Rescue angioplasty after thrombolysis.

PMID- 16615181
TI  - Rescue angioplasty after thrombolysis.

PMID- 16615182
TI  - Rescue angioplasty after thrombolysis.

PMID- 16615183
TI  - Abstracts of the 67th Annual Meeting of the Society for Investigative
      Dermatology, Philadelphia, Pennsylvania, USA, May 3-6, 2006.

PMID- 16615184
TI  - Intraperitoneal chemotherapy for ovarian cancer.

PMID- 16615185
TI  - Hypothermia for neonates with hypoxic-ischemic encephalopathy.

PMID- 16615186
TI  - Hypothermia for neonates with hypoxic-ischemic encephalopathy.

PMID- 16615187
TI  - Deaths from Clostridium sordellii after medical abortion.

PMID- 16615188
TI  - Deaths from Clostridium sordellii after medical abortion.

PMID- 16615189
TI  - Spectrometric determination of the refractive index of optical wave guiding
      materials used in lab-on-a-chip applications.
AB  - The design and optimization of light-based analytical devices often require
      optical characterization of materials involved in their construction. With the
      aim of benefiting lab-on-a-chip applications, a transmission spectrometric method
      for determining refractive indices, n, of transparent solids is presented here.
      Angular dependence of the reflection coefficient between material-air interfaces
      constitutes the basis of the procedure. Firstly, the method is studied via
      simulation, using a theoretical algorithm that describes the light propagation
      through the sample slide, to assess the potentially attainable accuracy.
      Simulations also serve to specify the angles at which measurements should be
      taken. Secondly, a visible light source and an optical fiber spectrometer are
      used to perform measurements on three commonly used materials in optical lab-on-a
      chip devices. A nonlinear regression subroutine fits experimental data to the
      proposed theoretical model and is used to obtain n. Because the attainable
      precision using this method of refractive index determination is dictated by the
      uncertainty in the transmission measurements, the precision (with 95% confidence)
      for mechanically rigid samples, namely glass and poly(methyl methacrylate)
      (PMMA), is higher than those estimated for the elastomer sample (in-house-molded
      poly(dimethylsiloxane) (PDMS)). At wavelengths with the highest signal-to-noise
      ratio for the spectrometer setup, the estimated refractive indices were 1.43+/
      0.05 (580 nm) for PDMS, 1.54+/-0.02 (546 nm) for glass, and 1.485+/-0.005 (656
      nm) for PMMA. Accurate refractive index estimations with an average precision
      equal to 0.01 refractive index units (RIU) were obtained for PMMA and glass
      samples, and an average precision of 0.09 RIU for the PDMS molded slide between
      550 and 750 nm was obtained.

PMID- 16615190
TI  - The application of chemical leasing business models in Mexico.
AB  - BACKGROUND, AIM AND SCOPE: To better address the requirements of the changing
      multilateral order, the United Nations Industrial Development Organization
      (UNIDO) Cleaner Production Programme, in 2004, developed the new Sustainable
      Industrial Resource Management (SIRM) approach. This approach is in accordance
      with the principles decided at the United Nations Conference on Environment and
      Development (UNCED) in Rio de Janeiro, Brazil in 1992. Unlike the traditional
      approaches to environmental management, the SIRM concept captures the idea of
      achieving sustainable industrial development through the implementation of
      circular material and energy flows in the entire production chain and reduction
      of the amount of material and energy used with greater efficiency solutions. The
      SIRM approach seeks to develop new models to encourage a shift from selling
      products to supplying services, modifying, in this manner, the supplier/user
      relationship and resulting in a win-win situation for the economy and the
      environment. Chemical Leasing represents such a new service-oriented business
      model and is currently being promoted by UNIDO's Cleaner Production Programme.
      MAIN FEATURES. One of the potential approaches to address the problems related to
      ineffective use and over-consumption of chemicals is the development and
      implementation of Chemical Leasing business models. These provide concrete
      solutions to the effective management of chemicals and on the ways negative
      releases to the environment can be reduced. The Chemical Leasing approach is a
      strategy that addresses the obligations of the changing international chemicals
      policy by focusing on a more service-oriented strategy. Mexico is one of the
      countries that were selected for the implementation of UNIDO's demonstration
      project to promote Chemical Leasing models in the country. The target sector of
      this project is the chemical industry, which is expected to shift their
      traditional business concept towards a more service and value-added approach.
      This is being achieved through the development of company specific business
      models that implement the above-indicated Chemical Leasing concept with the
      support from the Mexican National Cleaner Production Centre (NCPC). RESULTS AND
      CONCLUSIONS: The implementation of Chemical Leasing in Mexico has proven to be an
      efficient instrument in enhancing sustainable chemical management and
      significantly reducing emissions in Mexico. Several companies from the chemical
      industrial sector implement or agreed to implement chemical leasing business
      models. Based on the positive findings of the project, several Mexican companies
      started to negotiate contents of possible Chemical Leasing contracts with
      suitable business partners. The project further aimed at disseminating
      information on Chemical Leasing. It successfully attracted globally operating
      companies in the chemicals sector to explore possibilities to implement Chemical
      Leasing business models in Mexico. At the international level, the results of the
      UNIDO project were presented on 20th September 2005 during a side event of the
      Strategic Approach to International Chemicals Management (SAICM) Preparation
      Conference in Vienna. RECOMMENDATIONS AND OUTLOOK: To facilitate the promotion
      and application of Chemical Leasing project at international level, UNIDO is
      currently developing a number of tools to standardize Chemical Leasing projects.
      These include, among others, Chemical leasing contract models; Chemical Leasing
      data base to find partners for chemical leasing; and guidelines to implement
      Chemical Leasing projects and work programmes.

PMID- 16615191
TI  - [Castration gone wrong].

PMID- 16615192
TI  - [Bulk packaging, sales tax and other doubtful business].

PMID- 16615193
TI  - Pyoderma gangrenosum in a syringe driver site of a patient with non-Hodgkin's
      lymphoma.
AB  - A case of pyoderma gangrenosum, which occurred in a patient with non-Hodgkin's
      lymphoma, is described. The lesion started at a syringe driver site on the upper
      arm.

PMID- 16615194
TI  - Reporting of weighted event rates in Evidence-Based Nursing abstracts of
      systematic reviews.

PMID- 16615195
TI  - Evidence-based nursing: how far have we come? What's next?

PMID- 16615196
TI  - Patterns of tobacco use became an integral component of intimate partner
      relationships.

PMID- 16615197
TI  - Review: delays in help seeking for cancer symptoms related to recognition and
      interpretation of symptoms and fear of consultation and were affected by gender
      and sanctioning of help seeking.

PMID- 16615198
TI  - Conflicts within and between patients and health professionals characterised
      poorly controlled diabetes.

PMID- 16615199
TI  - 4 themes described the sexual concerns and educational needs of patients with an
      implantable cardioverter defibrillator.

PMID- 16615200
TI  - Distal radioulnar joint instability.

PMID- 16615201
TI  - Sustaining HIV testing in pregnancy- evaluation of routine offer of HIV testing
      in three London hospitals over 2 years.
AB  - This study sets out to examine how routine offers of HIV testing for pregnant
      women in ante-natal (prenatal) clinics are managed over time. Data was collected
      over two time periods (2002, 2004) from all women booking clinics at three London
      hospitals. Data from 3,560 women, comprising 2,710 in 2002 (time 1) and 850 in
      2004 (time 2) were gathered. Uptake of HIV testing, demographic variables, HIV
      associated risks, pregnancy variables and uptake of other ante-natal tests were
      monitored. In the later study, details of partner testing and time spent
      discussing HIV was monitored. HIV test uptake with routine offer (RCT) was high.
      There was a significant increase in HIV testing over time from 85 to 91%
      (p<0.0001). In 2004, significantly more women had been previously tested for HIV
      (25 versus 41%, p<0.0001), more women refused all other ante-natal tests (rubella
      [0 versus 4% p<0.0001], syphilis [1 versus 5%, p<0.0001], Haemoglobin [1 versus
      3%, p<0.0001], Down's syndrome [0 versus 13%, p<0.0001] and hepatitis B [1 versus
      5%, p<0.0001]). Significantly less women refused HIV test (15 versus 9%,
      p<0.0001). Initially, HIV was the most frequently refused test (15%), whereas at
      time 2 Down's syndrome tests were most frequently declined. At time 1, 2%
      declined any test. By time 2, 14% of the sample declined any test (p<0.0001).
      Three percent of women had an established HIV risk at time 1 and 6% at time 2.
      Women with risk factors were significantly less likely to accept testing at time
      2, but not at time 1 or not overall. Multivariable analysis was carried out to
      look at predictors of opting in and opting out of testing. At time 2 HIV test
      uptake was more likely if less than 3 min was spent discussing it (chi2=9.3,
      p=0.002). This information was not available at time 1. HIV testing in ante-natal
      care can be sustained over time. Challenges for the future relate to complex
      cases, test declining, ensuring that women with risk factors do not
      systematically decline and providing skills for midwives or referral pathways to
      deal with more demanding cases. It has been possible to normalise HIV testing.
      Women have responded with high HIV test uptake, but are also questioning other
      tests which were previously routinely offered.

PMID- 16615202
TI  - [Patient information. Chronic cholestasis].

PMID- 16615203
TI  - Spatial ecology of mating success in a sexually polymorphic plant.
AB  - The spatial context of reproduction is of crucial importance to plants because of
      their sessile habit. Since pollen and seed dispersal is often restricted, mating
      success is likely to depend on the quantity and quality of mates in local
      neighbourhoods. Here we use neighbourhood models to investigate the spatial
      ecology of pollination and mating in Narcissus assoanus, a sexually polymorphic
      plant with two mating morphs that differ in style length. By mapping individuals
      in eight populations from southwestern France, we investigated the influence of
      the density and morph identity of plants at different spatial scales on variation
      in female fertility. By using inferences on the expected patterns of pollen
      transfer based on floral morphology, we were able to predict the quantitative
      relations between local morph ratios and variation in fertility. Our analyses
      revealed differences in the spatial clustering of morphs and in their response to
      plant density and morph identity within local neighbourhoods. Mating success in
      N. assoanus was characterized by both density- and frequency-dependent processes,
      a condition that may be a general feature of the spatial ecology of plant mating.

PMID- 16615204
TI  - The introgression of a functional nuclear gene from Poa to Festuca ovina.
AB  - In sheep's fescue, Festuca ovina, genes coding for the cytosolic enzyme
      phosphoglucose isomerase, PGIC, are not only found at the standard locus, PgiC1,
      but also at a segregating second locus, PgiC2. We have used PCR-based sequencing
      to characterize the molecular structure and evolution of five PgiC1 and three
      PgiC2 alleles in F. ovina. The three PgiC2 alleles were complex in that they
      carried two gene copies: either two active genes or one active and one
      pseudogene. All the PgiC2 sequences were very similar to each other but highly
      diverged from the five PgiC1 sequences. We also sequenced PgiC genes from several
      other grass species. Phylogenetic analysis of these sequences indicates that
      PgiC2 has introgressed into F. ovina from the distant genus Poa. Such an
      introgression may, for example, follow from a non-standard fertilization with
      more than one pollen grain, or a direct horizontal gene transfer mediated by a
      plant virus.

PMID- 16615205
TI  - An unusual choanoflagellate protein released by Hedgehog autocatalytic
      processing.
AB  - Hedgehog proteins are important cell-cell signalling proteins utilized during the
      development of multicellular animals. Members of the hedgehog gene family have
      not been detected outside the Metazoa, raising unanswered questions about their
      evolutionary origin. Here we report a highly unusual hedgehog-related gene from a
      choanoflagellate, a close unicellular relative of the animals. The deduced C
      terminal domain, Hoglet-C, is homologous to the autocatalytic domain of Hedgehog
      proteins and is predicted to function in autocatalytic cleavage of the precursor
      peptide. In contrast, the N-terminal Hoglet-N peptide has no similarity to the
      signalling peptide of Hedgehog (Hh-N). Instead, Hoglet-N is deduced to be a
      secreted protein with an enormous threonine-rich domain of unprecedented size and
      purity (over 200 threonine residues) and two polysaccharide-binding domains.
      Structural modelling reveals that these domains have a novel combination of
      features found in cellulose-binding domains (CBD) of types IIa and IIb, and are
      expected to bind cellulose. We propose that the two CBD domains enable Hoglet-N
      to bind to plant matter, tethering an amorphous nucleophilic anchor, facilitating
      transient adhesion of the choanoflagellate cell. Since Hh-C and Hoglet-C are
      homologous, but Hh-N and Hoglet-N are not, we argue that metazoan hedgehog genes
      evolved by fusion of two distinct genes.

PMID- 16615206
TI  - Integrating life history and cross-immunity into the evolutionary dynamics of
      pathogens.
AB  - Models for the diversity and evolution of pathogens have branched into two main
      directions: the adaptive dynamics of quantitative life-history traits (notably
      virulence) and the maintenance and invasion of multiple, antigenically diverse
      strains that interact with the host's immune memory. In a first attempt to
      reconcile these two approaches, we developed a simple modelling framework where
      two strains of pathogens, defined by a pair of life-history traits (infectious
      period and infectivity), interfere through a given level of cross-immunity. We
      used whooping cough as a potential example, but the framework proposed here could
      be applied to other acute infectious diseases. Specifically, we analysed the
      effects of these parameters on the invasion dynamics of one strain into a
      population, where the second strain is endemic. Whereas the deterministic version
      of the model converges towards stable coexistence of the two strains in most
      cases, stochastic simulations showed that transient epidemic dynamics can cause
      the extinction of either strain. Thus ecological dynamics, modulated by the
      immune parameters, eventually determine the adaptive value of different pathogen
      genotypes. We advocate an integrative view of pathogen dynamics at the crossroads
      of immunology, epidemiology and evolution, as a way towards efficient control of
      infectious diseases.

PMID- 16615207
TI  - An evolutionary perspective on caching by corvids.
AB  - A principal finding in the food-caching literature is that species differences in
      hoarding propensity are positively correlated with species differences in degree
      of adaptations to caching behaviour, such as performance on spatial memory tasks
      and hippocampal volume. However, there are examples that do not fit this pattern.
      We argue that these examples can be better understood by considering the
      phylogenetic relatedness between species. We reconstruct the ancestral state for
      caching behaviour in corvids and assess when transitions in caching behaviour
      occurred within the corvid phylogeny. Our analysis shows that the common ancestor
      of all corvids was a moderate cacher. This result suggests that corvids followed
      a bi-directional evolutionary trajectory in which caching was secondarily lost
      twice and there were at least two independent transitions from moderate to
      specialized caching. The independent evolution of specialized cachers in the two
      groups must, therefore, be a case of convergent evolution. This is exemplified by
      the fact that specialized cachers show structurally different adaptations serving
      the same function to intense caching, such as different pouches to transport
      food. Finally, we argue that convergent evolution may have led to adaptations in
      memory and hippocampus that serve the same function but differ in design, and
      that these different adaptations may explain the examples that do not fit the
      pattern predicted by the adaptive specialization hypothesis.

PMID- 16615208
TI  - A shift to parasitism in the jellyfish symbiont Symbiodinium microadriaticum.
AB  - One of the outstanding and poorly understood examples of cooperation between
      species is found in corals, hydras and jellyfish that form symbioses with algae.
      These mutualistic algae are mostly acquired infectiously from the seawater and,
      according to models of virulence evolution, should be selected to parasitize
      their hosts. We altered algal transmission between jellyfish hosts in the
      laboratory to examine the potential for virulence evolution in this widespread
      symbiosis. In one experimental treatment, vertical transmission of algae (parent
      to offspring) selected for symbiont cooperation, because symbiont fitness was
      tied to host reproduction. In the other treatment, horizontal transmission
      (infectious spread) decoupled symbiont fitness from the host, potentially
      allowing parasitic symbionts to spread. Fitness estimates revealed a striking
      shift to parasitism in the horizontal treatment. The horizontally transmitted
      algae proliferated faster within hosts and had higher dispersal rates from hosts
      compared to the vertical treatment, while reducing host reproduction and growth.
      However, a trade-off was detected between harm caused to hosts and symbiont
      fitness. Virulence trade-offs have been modelled for pathogens and may be
      critical in stabilising 'infectious' symbioses. Our results demonstrate the
      dynamic nature of this symbiosis and illustrate the potential ease with which
      beneficial symbionts can evolve into parasites.

PMID- 16615209
TI  - Interactions between predator- and diet-induced phenotypic changes in body shape
      of crucian carp.
AB  - Predator cues and diet, when studied separately, have been shown to affect body
      shape of organisms. Previous studies show that the morphological responses to
      predator absence/presence and diet may be similar, and hence could confound the
      interpretation of the causes of morphological differences found between groups of
      individuals. In this study, we simultaneously examined the effect of these two
      factors on body shape and performance in crucian carp in a laboratory experiment.
      Crucian carp (Carassius carassius) developed a shallow body shape when feeding on
      zooplankton prey and a deep body shape when feeding on benthic chironomids. In
      addition, the presence of chemical cues from a pike predator affected body shape,
      where a shallow body shape was developed in the absence of pike and a deep body
      shape was developed in the presence of pike. Foraging activity was low in the
      presence of pike cues and when chironomids were given as prey. Our results
      thereby suggest that the change in body shape could be indirectly mediated
      through differences in foraging activity. Finally, the induced body shape changes
      affected the foraging efficiency, where crucians raised on a zooplankton diet or
      in the absence of pike cues had a higher foraging success on zooplankton compared
      to crucian raised on a chironomid diet or in the presence of pike. These results
      suggest that body changes in response to predators can be associated with a cost,
      in terms of competition for resources.

PMID- 16615210
TI  - Coprophagy in a cave-adapted salamander; the importance of bat guano examined
      through nutritional and stable isotope analyses.
AB  - During a two year population ecology study in a cave environment, 15 Eurycea (=
      Typhlotriton) spelaea were observed ingesting bat guano. Furthermore, E. spelaea
      capture numbers increased significantly during the time that grey bats (Myotis
      grisescens) deposited fresh guano. We investigated the hypothesis that this
      behaviour was not incidental to the capture of invertebrate prey, but a diet
      switch to an energy-rich detritus in an oligotrophic environment. Stable isotope
      assays determined that guano may be assimilated into salamander muscle tissue,
      and nutritional analyses revealed that guano is a comparable food source to
      potential invertebrate prey items. This is the first report of coprophagy in a
      salamander and in any amphibian for reasons other than intestinal inoculation.
      Because many temperate subterranean environments are often energy poor and this
      limitation is thought to select for increased diet breadth, we predict that
      coprophagy may be common in subterranean vertebrates where it is not currently
      recognized.

PMID- 16615211
TI  - A mechanistic link between chick diet and decline in seabirds?
AB  - A climatic regime shift during the mid-1970s in the North Pacific resulted in
      decreased availability of lipid-rich fish to seabirds and was followed by a
      dramatic decline in number of kittiwakes breeding on the Pribilof Islands.
      Although production of chicks in the mid-1970s was adequate to sustain kittiwake
      populations in the early 1980s, the disappearance of birds from breeding colonies
      apparently exceeded recruitment. No mechanism has been proposed to explain why
      recruitment would differ among fledglings fed lipid-rich or lipid-poor fish
      during development. Here we show that diets low in lipids induce nutritional
      stress and impair cognitive abilities in young red-legged kittiwakes, Rissa
      brevirostris. Specifically, growth retardation, increased secretion of stress
      hormones and inferior ability to associate food distribution with visual cues
      were observed in individuals fed lipid-poor diets. We conclude that lipid-poor
      diets during development affect the quality of young seabirds, which is likely to
      result in their increased mortality and low recruitment.

PMID- 16615212
TI  - Preservation of hypericin and related polycyclic quinone pigments in fossil
      crinoids.
AB  - The fringelite pigments, a group ofphenanthroperylene quinones discovered in
      purple coloured specimens of the Upper Jurassic crinoid Liliocrinus, demonstrate
      exceptional preservation of organic compounds in macrofossils. Here we report the
      finding of hypericin and related phenanthroperylene quinones in Liliocrinus
      munsterianus from the original 'Fringeli' locality and in the Middle Triassic
      crinoid Carnallicrinus carnalli. Our results show that fringelites in fact
      consist ofhypericin and closely related derivatives and that the stratigraphic
      range of phenanthroperylene quinones is much wider than previously known. The
      fossil occurrence of hypericin indicates a polyketide biosynthesis of hypericin
      type pigments in Mesozoic crinoids analogous to similar polyketides, which occur
      in living crinoids. The common presence of a characteristic distribution pattern
      of the fossil pigments and related polycyclic aromatic hydrocarbons further
      suggests that this assemblage is the result of a stepwise degradation of
      hypericin via a general diagenetic pathway.

PMID- 16615213
TI  - Sexual reproduction reshapes the genetic architecture of digital organisms.
AB  - Modularity and epistasis, as well as other aspects of genetic architecture, have
      emerged as central themes in evolutionary biology. Theory suggests that
      modularity promotes evolvability, and that aggravating (synergistic) epistasis
      among deleterious mutations facilitates the evolution of sex. Here, by contrast,
      we investigate the evolution of different genetic architectures using digital
      organisms, which are computer programs that self-replicate, mutate, compete and
      evolve. Specifically, we investigate how genetic architecture is shaped by
      reproductive mode. We allowed 200 populations of digital organisms to evolve for
      over 10 000 generations while reproducing either asexually or sexually. For 10
      randomly chosen organisms from each population, we constructed and analysed all
      possible single mutants as well as one million mutants at each mutational
      distance from 2 to 10. The genomes of sexual organisms were more modular than
      asexual ones; sites encoding different functional traits had less overlap and
      sites encoding a particular trait were more tightly clustered. Net directional
      epistasis was alleviating (antagonistic) in both groups, although the overall
      strength of this epistasis was weaker in sexual than in asexual organisms. Our
      results show that sexual reproduction profoundly influences the evolution of the
      genetic architecture.

PMID- 16615214
TI  - Costs of breeding and their effects on the direction of sexual selection.
AB  - A recent life-history model has challenged the importance of the operational sex
      ratio and the potential reproductive rates of males and females as the factors
      most important for the control of sexual selection, arguing that the cost of
      breeding, interpreted as the probability of dying as a consequence of the current
      breeding attempt, is the single most important factor that best predicts a mating
      system. In one species of bushcricket, the mating system can be reversed by
      resource manipulation. Here, we examine the costs of breeding in this system.
      Consistent with the model, increased costs of breeding can explain female
      competition and increased male choosiness under resource limitation. However,
      this is due to differences in the time required for a breeding attempt, rather
      than differences in breeding mortality which did not differ between the sexes. In
      general, males lived longer than females and we discuss the possible reasons
      behind this pattern of sex-biased non-breeding mortality.

PMID- 16615215
TI  - The human brain is a detector of chemosensorily transmitted HLA-class I
      similarity in same- and opposite-sex relations.
AB  - Studies on subjective body odour ratings suggest that humans exhibit preferences
      for human leucocyte antigen (HLA)-dissimilar persons. However, with regard to the
      extreme polymorphism of the HLA gene loci, the behavioural impact of the proposed
      HLA-related attracting signals seems to be minimal. Furthermore, the role of HLA
      related chemosignals in same- and opposite-sex relations in humans has not been
      specified so far. Here, we investigate subjective preferences and brain evoked
      responses to body odours in males and females as a function of HLA similarity
      between odour donor and smeller. We show that pre-attentive processing of body
      odours of HLA-similar donors is faster and that late evaluative processing of
      these chemosignals activates more neuronal resources than the processing of body
      odours of HLA-dissimilar donors. In same-sex smelling conditions, HLA-associated
      brain responses show a different local distribution in male (frontal) and female
      subjects (parietal). The electrophysiological results are supported by
      significant correlations between the odour ratings and the amplitudes of the
      brain potentials. We conclude that odours of HLA-similar persons function as
      important social warning signals in inter- and intrasexual human relations. Such
      HLA-related chemosignals may contribute to female and male mate choice as well as
      to male competitive behaviour.

PMID- 16615216
TI  - Genetic evidence for female-biased dispersal and gene flow in a polygynous
      primate.
AB  - Many models of sex-biased dispersal predict that the direction of sex-bias
      depends upon a species' mating system. In agreement with this, almost all
      polygynous mammals show male-biased dispersal whereas largely monogamous birds
      show female-biased dispersal (FBD). The hamadryas baboon (Papio hamadryas
      hamadryas) is polygynous and so dispersal is predicted to be male biased, as is
      found in all other baboon subspecies, but there are conflicting field data
      showing both female and male dispersal. Using 19 autosomal genetic markers
      genotyped in baboons from four Saudi Arabian populations, we found strong
      evidence for FBD in post-dispersal adults but not, as expected, in pre-dispersal
      infants and young juveniles, when we compared male and female: population
      structure (F(st)), inbreeding (F(is)), relatedness (r), and the mean assignment
      index (mAIc). Furthermore, we found evidence for female-biased gene flow as
      population genetic structure (F(st)), was about four times higher for the
      paternally inherited Y, than for either autosomal markers or for maternally
      inherited mtDNA. These results contradict the direction of sex-bias predicted by
      the mating system and show that FBD has evolved recently from an ancestral state
      of male-biased dispersal. We suggest that the cost-benefit balance of dispersal
      to males and females is tightly linked to the unique hierarchical social
      structure of hamadryas baboons and that dispersal and social organization have
      coevolved.

PMID- 16615217
TI  - How effective are maternal effects at having effects?
AB  - The well studied trade-off between offspring size and offspring number assumes
      that offspring fitness increases with increasing per-offspring investment. Where
      mothers differ genetically or exhibit plastic variation in reproductive effort,
      there can be variation in per capita investment in offspring, and via this trade
      off, variation in fecundity. Variation in per capita investment will affect
      juvenile performance directly--a classical maternal effect--while variation in
      fecundity will also affect offspring performance by altering the offsprings'
      competitive environment. The importance of this trade-off, while a focus of
      evolutionary research, is not often considered in discussions about population
      dynamics. Here, we use a factorial experiment to determine what proportion of
      variation in offspring performance can be ascribed to maternal effects and what
      proportion to the competitive environment linked to the size-number trade-off.
      Our results suggest that classical maternal effects are significant, but that in
      our system, the competitive environment, which is linked to maternal environments
      by fecundity, can be a far more substantial influence.

PMID- 16615218
TI  - Hypervariable prophage WO sequences describe an unexpected high number of
      Wolbachia variants in the mosquito Culex pipiens.
AB  - Wolbachia are maternally inherited endosymbiotic bacteria that infect many
      arthropod species and may induce cytoplasmic incompatibility (CI) resulting in
      abortive embryonic development. Among all the described host species, mosquitoes
      of the Culex pipiens complex display the highest variability of CI crossing
      types. Paradoxically, searches for polymorphism in Wolbachia infecting strains
      and field populations hitherto failed or produced very few markers. Here, we show
      that an abundant source of the long-sought polymorphism lies in WO prophage
      sequences present in multiple copies dispersed in the genome of Wolbachia
      infecting C. pipiens (wPip). We identified up to 66 different Wolbachia variants
      in C. pipiens strains and field populations and no occurrence of superinfection
      was observed. At least 49 different Wolbachia occurred in Southern Europe C.
      pipiens populations, and up to 10 different Wolbachia were even detected in a
      single population. This is in sharp contrast with North African and Cretan
      samples, which exhibited only six variants. The WO polymorphism appeared stable
      over time, and was exclusively transferred maternally. Interestingly, we found
      that the CI pattern previously described correlates with the variability of Gp15,
      a prophage protein similar to a bacterial virulence protein. WO prophage
      sequences thus represent variable markers that now open routes for approaching
      the molecular basis of CI, the host effects, the structure and dynamics of
      Wolbachia populations.

PMID- 16615219
TI  - The brainstem reticular formation is a small-world, not scale-free, network.
AB  - Recently, it has been demonstrated that several complex systems may have simple
      graph-theoretic characterizations as so-called 'small-world' and 'scale-free'
      networks. These networks have also been applied to the gross neural connectivity
      between primate cortical areas and the nervous system of Caenorhabditis elegans.
      Here, we extend this work to a specific neural circuit of the vertebrate brain-
      the medial reticular formation (RF) of the brainstem--and, in doing so, we have
      made three key contributions. First, this work constitutes the first model (and
      quantitative review) of this important brain structure for over three decades.
      Second, we have developed the first graph-theoretic analysis of vertebrate brain
      connectivity at the neural network level. Third, we propose simple metrics to
      quantitatively assess the extent to which the networks studied are small-world or
      scale-free. We conclude that the medial RF is configured to create small-world
      (implying coherent rapid-processing capabilities), but not scale-free, type
      networks under assumptions which are amenable to quantitative measurement.

PMID- 16615220
TI  - The first 20 years of heart transplantation in Ireland.
AB  - BACKGROUND: The first Irish heart transplant was performed on the 10th of
      September 1985. Over the next 20 years, 229 transplants were performed in 228
      recipients. AIMS: To evaluate the success of the first generation of cardiac
      transplantation in Ireland. METHODS: Analysis of clinical outcomes and survival
      statistics for patients undergoing heart transplantation in Ireland and
      comparison with international standards. RESULTS: There has been a steady
      improvement in transplant outcome over this time and survival figures for
      recipients between 2000 and 2004 show a hospital, 1-year and 5-year survival rate
      of 85.7%, 84.1% and 76.8% respectively. Thirty-eight of the 99 heart transplants
      performed between 1985 and 1994 are still alive more than 10 years later and the
      longest survivor is now 19 years post transplantation. CONCLUSIONS: The results
      compare favourably with international figures. Heart transplantation offers
      excellent longterm survival and quality of life but remains challenged by a
      shortage of suitable donor organs.

PMID- 16615221
TI  - Co-immunotherapy with interleukin-2 and taurolidine for progressive metastatic
      melanoma.
AB  - BACKGROUND: Recombinant interleukin-2(rIL-2) therapy in metastatic melanoma is
      limited by toxicities, particularly vascular leak syndrome(VLS). Taurolidine
      potentiates the anti-neoplastic effects of IL-2 while reducing its associated
      endothelial cell dysfunction in experimental settings. We hypothesized that co
      administration of rIL-2 with taurolidine could enhance tolerability without
      weakening effectiveness. METHODS: Eleven patients with progressive metastatic
      melanoma received high-dose rIL-2 with co-infusion of taurolidine. Patients were
      monitored for the development of toxicities and evidence of response. RESULTS:
      Ten patients tolerated twenty-nine courses of high-dose rIL-2 without dose
      reduction. Most toxicities were low-grade. No patient developed VLS. Seven
      patients died from disease progression. Two had complete clinical and
      radiological responses to treatment. Two patients remain alive despite evidence
      of disease progression a mean of 17.5 months after diagnosing metastatic disease.
      CONCLUSION: Co-administration of taurolidine with high-dose rIL-2 in stage IV
      melanoma patients appears to greatly enhance the tolerability of this regime
      without diminishing its therapeutic value.

PMID- 16615222
TI  - Virtual reality technology and surgical training--a survey of general surgeons in
      Ireland.
AB  - BACKGROUND: Virtual Reality Technology (VRT) is a validated method of training in
      industry but only recently has found a place in the postgraduate surgical
      curriculum. AIMS: We surveyed 143 Irish consultant surgeons to ascertain their
      opinions on this topical issue. METHODS: The survey consisted of 22 questions to
      which the consultants were asked to respond by choosing from a 5-point Likert
      scale. RESULTS: Sixty-five per cent responded. A majority of 72% had seen VRT but
      only 47% had 'hands on' experience. Forty-six per cent believed that they were
      poorly informed regarding available technologies. As consultants became more
      informed about VRT significant differences were seen with regard to attitudes
      regarding the role of VR in skills in surgical training (p<0.05) and in the
      ability to define teaching objectives (p<0.005). CONCLUSIONS: Our survey suggests
      that the underuse of the current offerings is not due to a perceived lack of
      interest on the part of the surgical trainers. Suppliers of these programmes have
      a responsibility to adequately educate and collaborate with all parties involved
      to improve overall benefit from these simulators.

PMID- 16615223
TI  - Trends in RTA related spinal injuries: the post penalty points era.
AB  - BACKGROUND: On October 31st 2002 a system of cumulative penalty points for road
      traffic offences was introduced. Early evidence suggested a reduction in road
      traffic accident (RTA) related morbidity. AIMS: To evaluate the persistence of
      the initial reduction in RTA related spinal injuries following penalty points
      introduction. METHODS: Retrospective review of all acute spinal trauma admissions
      to the NSIU between November 1st 1998 and October 31st 2004 (n = 966). Patient
      demographics and injury aetiology were assessed. Follow-up questionnaires
      evaluated RTA circumstances. RESULTS: RTA related spinal injuries accounted for
      39.3% of NSIU admissions. These injuries were significantly more common in males
      aged 16-24, drivers (70.8%), on routine journeys (77.5%) and rural roads (48.8%).
      The highest proportion of accidents occurred during weekends (64.3% from Fri-Sun)
      and from midnight to 6am (29.3%). CONCLUSIONS: The initial reduction in RTA
      related spinal injuries has not been sustained. Young male drivers are the
      greatest at risk group.

PMID- 16615224
TI  - Demands for vascular access in a renal dialysis unit: implications for a regional
      vascular unit.
AB  - BACKGROUND: The development of regional dialysis units and the expanding
      indications for dialysis has led to increased demand for vascular access surgery.
      Consequently, the provision and maintenance of access, and the management of
      related complications has created a considerable burden on vascular surgical
      units in hospitals providing renal replacement therapy (RRT). AIMS: The
      objectives of our study were to review our experience with a variety of vascular
      access modalities for haemodialysis and to quantify the associated surgical
      workload. METHODS: We reviewed our experience in a consecutive group of dialysis
      patients who had access surgery for RRT in a regional hospital setting. RESULTS:
      Between January 1995 and January 2000, 69 patients entered the long-term dialysis
      programme in the Mid-Western region (population = 320,000). Of the 158 procedures
      performed, 138 (87%) were for access creation, and 20 (13%) related to access
      revision procedures. Twenty patients (29%) developed a total of 30 access related
      complications. Vascular access procedures accounted for 10% of the vascular
      surgical workload (1598 procedures) in the five-year period. CONCLUSION: Vascular
      access is an important part of the haemodialysis services and surgical expertise
      should be available at local level to cope with likely demand.

PMID- 16615225
TI  - Smoking profile of non-consultant hospital doctors.
AB  - BACKGROUND: In 1994 Doll and colleagues published smoking mortality figures for
      British doctors over 40 years. AIMS: To assess smoking prevalence among junior
      doctors in a major Dublin teaching hospital. METHODS: One hundred and fourteen
      non-consultant doctors (NCHDs) at St James's Hospital received a confidential
      smoking questionnaire. RESULTS: One hundred and six NCHDs responded (93%). Three
      refused, five were not available. Ninety per cent were aged 24-35 years. Twenty
      six per cent of the doctors had smoked for 10 to 15 years. Seventy-five per cent
      were smoking more than 10 cigarettes daily. Ninety-seven per cent (20) of smokers
      wanted to stop smoking. Seventy-four per cent (17) had unsuccessfully attempted
      to quit. The smoking cessation method most commonly used was'cold turkey' in 60%.
      Others included nicotine replacement, bupropion and hypnotherapy. CONCLUSION: A
      significant per centage of NCHDs (22%) continue to smoke, despite overwhelming
      evidence that this causes health problems. The prevalence in our study is lower
      than the national figure of 29%.

PMID- 16615226
TI  - The celtic coincidence--the frequency and clinical characterisation of hereditary
      haemochromatosis in patients with coeliac disease.
AB  - BACKGROUND: Hereditary Haemochromatosis (HH) and Coeliac disease (CD) are common
      disorders in Northern European populations, particularly the Irish population.
      AIMS: To investigate whether there was increased frequency of the two common HFE
      gene mutations, C282Y and H63D, associated with HH amongst a cohort of CD
      patients, and to determine the penetrance of the HH associated genotypes in this
      cohort. METHODS: HFE genotypes of a cohort of CD patients were determined using
      standard PCR techniques. HFE allele frequencies were compared to those of a
      previously reported, ethnically similar, cohort of 800 neonates, using Fishers
      exact test. Patients with HH-associated genotypes were subsequently evaluated.
      RESULTS: The C282Y and H63D allele frequencies, 24/222 (11%) and 28/222 (13%)
      respectively, in the CD patients were similar to those of the neonatal group,
      171/1600 (11%) and 242/1600 (15%). Eight patients had HH-associated genotypes, of
      which two demonstrated biochemical evidence of iron overload. CONCLUSION: The HFE
      mutations associated with Hereditary Haemochromatosis are not more common in
      Irish CD patients.

PMID- 16615227
TI  - Lessons learned using Snodgrass hypospadias repair.
AB  - BACKGROUND: This is a review of our experience with the Snodgrass technique for
      distal hypospadias repair and we point to lessons learned in improving results.
      METHODS: We reviewed all patients who underwent Snodgrass hypospadias repair for
      distal hypospadias over a four-year period by a single surgeon. Chart review
      followed by parental telephone interview was used to determine voiding function,
      cosmesis and complication rate. RESULTS: Thirty children and three adults were
      identified. Age at surgery ranged from seven months to 39 years. The urinary
      stream was straight in 94%, and 97% reported a good or satisfactory final
      cosmetic outcome. One patient (3.3%) developed a urethral fistula and 21%
      developed meatal stenosis which required general anaesthetic. CONCLUSION: The
      Snodgrass urethroplasty provides satisfactory cosmetic and functional results.
      High rates of meatal stenosis initially encountered have improved with
      modifications to technique which include modified meatoplasty and routine meatal
      dilatation by the parents.

PMID- 16615228
TI  - Aorto-enteric fistula: changing management strategies.
AB  - BACKGROUND: Traditionally treatment of aorto-enteric fistulae involved placement
      of an extra-anatomic bypass and graft excision. This is associated with limb loss
      (10-40%) and high mortality (10-70%). More recently in situ revascularisation has
      been advocated. AIMS: To examine our experience with the changing management of
      aorto-enteric fistulae over a 22-year period. METHODS: Demographic, clinical,
      operative and pathological data were recorded retrospectively. RESULTS: Twenty
      one patients were included. Seven had primary fistulae. Six died prior to
      intervention. Five had an extra-anatomical bypass (60% mortality, 40% limb loss),
      four had in-situ revascularisation (25% mortality), four had a primary repair
      (25% mortality) and two had insertion of a tube graft (primary fistulae). The
      overall survival rate was 38%. The postoperative survival rate was 6o%.
      CONCLUSION: Techniques for operative management continue to evolve. The current
      trend is towards a local surgical approach with prolonged and intensive
      postoperative antimicrobial therapy. In our experience this approach has yielded
      acceptable outcomes.

PMID- 16615229
TI  - Vaginal cytology following primary hysterectomy for cervical cancer: is it
      useful?
AB  - BACKGROUND: Vaginal intraepithelial neoplasia (VAIN) is usually detected in
      patients with synchronous or antecedent cervical or vulval intraepithelial or
      invasive cancer. VAIN has the potential to progress to malignancy. AIMS: To
      determine the incidence and severity and analyse the management of vaginal
      dysplasia in patients undergoing primary hysterectomy for cervical cancer.
      METHODS: A retrospective study (1984-1998) identified 210 primary invasive
      cervical cancers. One-hundred and twenty-three patients had a primary
      hysterectomy. RESULTS: In follow-up six patients were found to have dyskaryosis
      in a second vaginal smear. Biopsies in the six patients with colposcopic lesions
      showed VAIN II (n=2), VAIN III (n=1),VAIN III / possible early invasion (n = 1)
      and invasive carcinoma (n=2). One patient with recurrent squamous cancer received
      salvage radiotherapy and one with recurrent adenocarcinoma received high dose
      progestogens and topical 5-fluorouracil. CONCLUSION: All patients are disease
      free at follow-up.

PMID- 16615230
TI  - Percutaneous vertebroplasty--initial clinical experience in osteoporotic and
      myelomatous compression fractures.
AB  - BACKGROUND: To review the clinical impact of vertebroplasty in osteoporotic and
      myelomatous compression fractures METHODS: Eleven compression fractures in eight
      patients were treated by percutaneous cement vertebroplasty over a three-year
      period, May 2000 to May 2003. RESULTS: Successful percutaneous stabilisation and
      cement injection was performed in all compression fractures. In five of eight
      patients (eight of eleven compression fractures) injection of cement yielded
      dramatic reduction in pain within 24 hours of the procedure. CONCLUSION:
      Preliminary experience suggests that percutaneous cement vertebroplasty is an
      effective well tolerated method of stabilisation of spinal wedge compression
      fractures resulting in dramatic reduction in associated pain in most cases.

PMID- 16615231
TI  - How well is peripheral neuropathy investigated? An audit from a regional
      neurophysiology department.
AB  - BACKGROUND: Peripheral neuropathy (PN) is common and increases with age. AIM: To
      assess how patients with confirmed peripheral neuropathy on nerve conduction
      studies (NCS) were investigated and to determine whether there was any difference
      in investigation based on patient age or referral source. DESIGN: Retrospective
      audit. METHODS: All EMG/NCS reports from a one-year period were analysed. The
      computer laboratory system was used to determine which blood tests had been
      performed on those patients with confirmed peripheral neuropathy on NCS. RESULTS:
      Over 50% of patients referred from within the hospital did not have a basic blood
      screen to search for the aetiology. There was no significant difference in
      investigation practise based on patient age or referral source. CONCLUSION: Our
      results highlight the lack of systematic investigation in a university teaching
      hospital. As a result of this audit, a protocol has been prepared and is
      distributed with NCS/EMG reports.

PMID- 16615232
TI  - Prospective evaluation of the efficacy of dermal botulinium toxin for primary
      axillary hyperhidrosis.
AB  - BACKGROUND: Primary axillary hyperhidrosis (PAH) is an embarassing, socially
      disabling condition, most commonly seen in young people. Previous treatments for
      this condition have included sympathectomy or axillary skin excision. Recently
      botulinum toxin has been used to provide effective, non-invasive treatment for
      this condition. AIMS: To investigate the effect of botulinum toxin injection in
      patients with PAH on sweat production and psychological wellbeing. METHODS: Ten
      patients were assessed before treatment with botulinum toxin injection using
      gravimetric analysis and a psychometric questionnaire. Patients were reassessed
      at intervals of one, four and twelve weeks following treatment. RESULTS:
      Injection with botulinum toxin resulted in significant improvement in patients
      physical symptoms and psychological wellbeing. However, improvement was short
      lived with recurrence of symptoms at three months. CONCLUSION: Botulinum toxin
      injection provides very effective short-term relief of PAH. While its limitations
      should be recognised and explained when consenting patients for treatment, this
      does not necessarily diminish its value in the treatment of PAH.

PMID- 16615233
TI  - Abdominal compartment syndrome.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) is a systemic syndrome involving
      derangement in cardiovascular haemodynamics, respiratory and renal functions as a
      result of sustained increase in intra-abdominal pressure (IAP) ending in multi
      organ failure. It is a life threatening emergency and requires prompt action and
      treatment. For the last 20 years, there has been more awareness among surgeons
      and intensivists of ACS being a distinct disease entity but still widespread
      ignorance prevails. Presentation can be acute, chronic and acute on chronic.
      Initial diagnosis is clinical, confirmed by measurement of IAP. Treatment is
      abdominal decompression by laparostomy and delayed abdominal closure. Despite
      prompt treatment mortality remains high. Awareness among surgeons has increased
      because laparoscopy has resulted in determination of IAP as a readily measurable
      quantity and also they have been able to appreciate the benefit of abdominal
      decompression by performing repeated planned laparotomies for trauma. METHODS: A
      medline, pubmed and Cochrane database search was performed and the articles found
      were cross referenced. RESULTS AND CONCLUSION: Clinical diagnosis is not easy and
      serial urinary bladder pressure (UBP) monitoring leads to early diagnosis.
      Treatment is by laprostomy to decompress the abdomen followed by delayed
      abdominal closure.

PMID- 16615234
TI  - Cutaneous lesions, not just skin deep!
AB  - BACKGROUND: Cutaneous metastatic disease is not unusual but it may mimic
      inflammatory lesions. The growth pattern of skin metastases is unpredictable and
      may differ from that of the primary tumour. Skin metastases may present as
      rapidly growing, solitary sessile or polypoid vascular nodules that ulcerate or
      bleed. AIM: To investigate the presenting complaints, surgical treatment and
      outcome of patients with cutaneous metastatic disease. METHODS: We present three
      cases of metastatic skin cancer recently seen in our Department and review the
      clinical and pathological findings. RESULTS: The finding of metastatic skin
      cancer is associated with a very poor prognosis and suggests widespread disease
      dissemination. CONCLUSION: The paper emphasizes the importance of excisional
      biopsy and accurate tissue diagnosis of skin nodules.

PMID- 16615235
TI  - Primary abdominal wall clear cell carcinoma arising in a Caesarean section scar
      endometriosis.
AB  - BACKGROUND: Endometriosis occurring in a surgical scar is well recognized and
      occurs mainly in patients with a history of hysterectomy or Caesarean section.
      Scar endometriosis, as well as endometriosis at other sites, can undergo
      malignant change. Endometrioid carcinoma is the most common malignant tumour
      arising in endometriosis. However, clear cell carcinoma can also occur but is
      unusual. AIM: To discuss the diagnosis and management of such a case. METHODS: We
      report a case of primary clear cell carcinoma in endometriosis of a Caesarean
      section scar and review the literature. RESULTS: The patient presented with a
      large right lower quadrant abdominal wall mass within a Caesarean section scar.
      Histological examination revealed a clear cell carcinoma. The patient had a prior
      history of pelvic endometriosis. According to the Irish National Cancer Registry,
      this is the first reported case of a primary abdominal wall clear cell carcinoma
      developing within a Caesarean section scar in Ireland. CONCLUSION: Any lesion
      occurring in a Caesarean section scar with a history of previous endometriosis
      cannot be underestimated and warrants careful clinical follow-up and histological
      evaluation as appropriate.

PMID- 16615236
TI  - Atrial fibrillation precipitated by carotid sinus massage in a patient with
      unexplained syncope.
AB  - BACKGROUND: Carotid sinus massage (CSM) is a useful tool in the investigation of
      unexplained syncope, but is associated with risks. AIM: To describe the first
      reported case of atrial fibrillation precipitated by CSM during the investigation
      of a patient with recurrent unexplained syncope. RESULTS: A 58-year-old female
      underwent CSM as part of a tilt test protocol for the investigation of recurrent
      unexplained syncope. Left CSM revealed the diagnosis of mixed cardioinhibitory
      and vasodepressor carotid sinus syndrome but also precipitated atrial
      fibrillation, an arrhythmia previously unreported as a complication of the
      procedure. CONCLUSIONS: CSM is a useful tool in the investigation of patients
      with recurrent unexplained syncope, but may cause atrial fibrillation in addition
      to other previously described complications and should, therefore, be used with
      caution.

PMID- 16615237
TI  - Facial nerve schwannoma of the internal auditory canal.
AB  - BACKGROUND: Facial nerve schwannoma of the internal auditory canal is a very rare
      tumour. AIM: While Bell's palsy is the commonest cause of a facial paresis, more
      serious causes should be excluded if recovery is delayed. METHOD: A case report
      of a young man who presented with a long standing facial palsy. CONCLUSION: Any
      facial palsy that does not show evidence of recovery within six weeks should be
      investigated radiologically to exclude a tumour.

PMID- 16615238
TI  - Hypospadias associated undescended testis in a Spigelian hernia.
AB  - BACKGROUND: First described in 1764, Spigelian hernias are rare. The patient
      profile is of an overweight, 50-year-old with associated respiratory disease.
      However we report the case of a four-month-old, with an associated hypospadias
      and cryptorchidism, where the testis was lying in a spigelian hernia. AIMS: To
      highlight this unusual presentation of cryptorchidism. CONCLUSION: Embryological
      development is a complex event that relies on the sequencing of hormonal surges
      for anatomical development. In this case report we postulate that the findings
      are secondary to hormonal disruption.

PMID- 16615239
TI  - Unicentric Castleman's disease: a surprising neck mass.
AB  - BACKGROUND: We present the case of a 36-year-old female with a three-week history
      of a pulsatile, tender mass in the anterior triangle of the neck. METHODS:
      Radiology demonstrated that this was a vascular tumour deep to the
      sternocleidomastoid muscle. RESULTS: Pre-operative embolisation and complete
      surgical resection was performed. Histology revealed Castleman's disease.
      CONCLUSION: Unicentric hyaline vascular Castleman's disease is an unusual cause
      of neck mass. Surgical resection remains the best chance for cure in unicentric
      disease. Long term follow-up is necessary as the risk of subsequent malignancy
      exists.

PMID- 16615240
TI  - Pseudoaneurysm of the cystic artery: a diagnostic dilemma and rare cause of
      haemobilia.

PMID- 16615241
TI  - Longevics: genetic lessons for the ages.

PMID- 16615242
TI  - Trauma and posttraumatic reactions in German development aid workers: prevalences
      and relationship to social acknowledgement.
AB  - BACKGROUND: While on duty abroad developmental aid workers (DAWs) are at risk of
      being traumatised. We investigated the prevalence of traumatic events,
      posttraumatic stress disorder (PTSD) and subsyndromal PTSD as well as
      associations with duty features and the psychological variable of social
      acknowledgement as victim or survivor. METHOD: A total of 312 developmental aid
      workers from the governmental German Development Service (DED) were surveyed by
      use of a trauma list, demographic questionnaire, the Posttraumatic Diagnostic
      Scale (PDS) and the Social Acknowledgement Questionnaire (SAQ). In addition,
      participants answered an open question concerning the amelioration of the DED's
      care provision. RESULTS: Some 47% of the surveyed DAWs had experienced and 7% of
      them had witnessed traumatic events while on duty abroad. A total of 16%
      developed either full or partial PTSD with the highest conditional PTSD
      probability after rape (33%) and life-threats (23%). Experience of traumatic
      events was correlated to duration of duties and number of duties, while PTSD
      symptomatology was associated with self-perceived general disapproval as a trauma
      victim. CONCLUSIONS: DAWs on duty in foreign countries experience more traumatic
      events compared with other German representative population samples. PTSD
      prevalences are also higher than those of German population samples. The
      association between rejection as a victim of trauma and PTSD severity indicates a
      possible starting-point for the development of PTSD prevention specific to this
      profession. Implications of the study are discussed with regard to participants'
      suggestions on how to handle traumatic experiences while on duty abroad.

PMID- 16615243
TI  - The measurement of social disablement and assessment of psychometric properties
      of the Social Behaviour Schedule (SBS-BR) in 881 Brazilian long-stay psychiatric
      patients.
AB  - BACKGROUND: Data on the prevalence of social disablement in long-stay psychiatric
      patients, and the assessment of the psychometric properties of the instruments
      that evaluate social behaviour in this population are scarce in Brazil.
      Therefore, this cross-sectional study aimed to estimate the prevalence rates of
      social disablement in a population of long-stay psychiatric patients from the Rio
      de Janeiro metropolitan area, and assessed the psychometric properties of the
      Social Behaviour Schedule (SBS). METHOD: Data were collected from a population of
      881 psychiatric patients housed in the Municipal Mental Health Institute using
      the 21-item SBS. RESULTS: Most of the patients were women (59%), the mean age was
      65.8 years (SD = 11) and the mean length of stay was 37.3 years (SD = 11.5). Of
      the population, 50.6% were scored as having poor self-care, 46% with little
      spontaneous communication, 41.1% with poor attention span, and 37.1% with
      underactivity. Comparing our data with international studies that used the same
      instrument, we found that our population was more disabled than the others,
      especially on the social withdrawal factor. Regarding psychometric properties,
      the inter-rater kappa was 0.709, the inter-informant kappa was 0.500, and the
      Cronbach's alpha coefficient was 0.766. The groups of patients in the six
      settings of the institute presented significant statistical differences in the
      total score (F = 11.447, p < 0.001). CONCLUSIONS: This study demonstrates the
      high rates of social disablement in this population. The precarious conditions of
      the institution where the patients have been living for decades and unmet
      individual care may have exacerbated their social disablement. Furthermore, the
      SBS-BR had satisfactory psychometric properties, particularly reliability,
      showing it to be an adequate instrument for measuring social disablement in
      Brazil.

PMID- 16615244
TI  - Optimism and pessimism in Kuwaiti and American college students.
AB  - BACKGROUND: Cross-cultural comparisons in optimism (O) and pessimism (P) are few.
      Kuwait and the United States have different languages, situations, history and
      culture. On this basis, there is good reason to hypothesise that there are
      significant differences between the two countries in O and P. AIMS: To explore
      the differences in, and correlates of, O and P in Kuwaiti and American college
      students. METHOD: Two samples of male and female undergraduates were recruited
      from Kuwait (N = 460) and the United States (N = 273). Their mean ages were 21.9
      +/- 3.0 and 23.2 +/- 6.5, respectively. All respondents completed the Arabic
      Scale of Optimism and Pessimism (ASOP), the Suicidal Ideation Questionnaire, the
      Ego-grasping Scale, the Death Obsession Scale, the Kuwait University Anxiety
      Scale and the Arabic Obsessive-Compulsive Scale. Kuwaitis responded to the scales
      in Arabic, and Americans responded in English. RESULTS: The ASOP displayed good
      internal consistency, a meaningful factorial structure and interpretable factors
      in both countries. It was found that O correlated negatively with the above scale
      scores, while the correlations of P were positive, indicating the convergent
      validity of the ASOP. The Kuwaiti mean score on O was significantly lower than
      the mean of their American counterparts, and vice versa for P. CONCLUSION: The
      findings are explained in the light of previous results on personality and
      psychopathology questionnaires in Kuwaiti and American societies. There is a need
      to investigate O and P in different cultures.

PMID- 16615245
TI  - Psychometric properties of a Persian-language version of the Automatic Thoughts
      Questionnaire: ATQ-Persian.
AB  - AIMS: To examine the psychometric properties of a Persian-language version of
      Hollon and Kendall's (1980) Automatic Thoughts Questionnaire (ATQ-Persian)--a
      measure of negative automatic thoughts in depression. METHODS: In a sample of 125
      student volunteers from two Iranian universities we assessed the internal
      consistency and test-retest reliability of ATQ-Persian, and examined its
      concurrent validity against the Beck Depression Inventory (Beck et al., 1996). We
      also examined the factor structure of the test through comparing the fit of
      various proposed factor-analytic models to the data using confirmatory factor
      analysis. RESULTS: ATQ-Persian had excellent internal consistency (Cronbach's
      alpha = 0.96), test-retest reliability (r = 0.84) and correlation with the Beck
      Depression Inventory (r = 0.77). Using a receiver operating characteristics
      curve, a score of 53 on ATQ-Persian was associated with a sensitivity of 89% and
      a specificity of 78% for detecting moderate to severe depression defined through
      Beck Depression Inventory. None of the proposed factorial models fitted the data
      well. However, models with correlated factors generally provided better fit than
      models with orthogonal factors, suggesting that the latent factors underlying ATQ
      Persian are highly correlated. CONCLUSIONS: These data support the reliability
      and validity of ATQ-Persian as a measure of negative automatic thoughts in
      depression.

PMID- 16615246
TI  - Suicide risk in relation to social class: a national register-based study of
      adult suicides in Korea, 1999-2001.
AB  - BACKGROUND: Few controlled studies have examined social class as a risk factor
      for suicide in Korea. AIM: The objective of the present study was to investigate
      the effects of social class on suicide risk in Korea. METHODS: A case-control
      design was constructed from cause-of-death statistics for the period 1999 to
      2001, in Korea, as published by the Korean National Statistical Office. The cases
      were defined as people aged between 20 and 64 who died by suicide, while the
      controls were defined as those who died of natural causes in the same age groups.
      RESULTS AND CONCLUSIONS: The proportions and odds ratios for suicide were higher
      in young people than in elderly people, and higher for divorced subjects than for
      cohabitants. They were also higher for residents of rural areas, as opposed to
      residents of Seoul and other metropolitan areas, and for people in social classes
      III and IV, than they were for those in social class I. To control the variables
      that influence risk of suicide, such as age, marital status and area of
      residence, we used multiple logistic regression. Compared with class I, risk of
      suicide was higher in social classes III and IV, in both sexes. The principal
      conclusion of this study is that, regardless of sex, lower social class
      constitutes a high risk for suicide in Korea, even after controlling for
      variables such as age, marital status and area of residence. We conclude that a
      well-controlled and balanced social welfare system could reduce suicide risk,
      especially among people in lower social class.

PMID- 16615247
TI  - Homelessness and mental illness: a literature review and a qualitative study of
      perceptions of the adequacy of care.
AB  - BACKGROUND: Homelessness and mental illness together confer significant morbidity
      and mortality because of physical health problems. Healthcare provision is
      undergoing significant review, and, as part of the Department of Health's policy
      reforms, the service user's view is central to the future restructuring of NHS
      services. MATERIAL: A literature review of homeless service users' perceptions of
      services for homeless mentally ill people was supplemented by a qualitative in
      depth survey of 10 homeless people. This article reports on their views about the
      services they receive. Mismatch between expectations and provision, disputes with
      healthcare providers, dissatisfaction with the degree to which they have choice
      in their care, and suspicions about the intentions of health professionals
      demonstrate the extent to which powerlessness and social exclusion are replicated
      in healthcare economies. The inadequacy of hostels and their staff are also
      emphasised, with some recommendations for services. DISCUSSION AND CONCLUSIONS:
      There are few data on homeless people's perceptions of services for mental health
      problems. Homeless people have strong views about the adequacy of services to
      meet their needs. They were particularly concerned about stigma, prejudice and
      the inadequacy and complexity of services that they have to use. This article
      reports their recommendations for change.

PMID- 16615248
TI  - The relationship between biogenetic causal explanations and social distance
      toward people with mental disorders: results from a population survey in Germany.
AB  - AIMS: Several studies have found an inverse relationship between people's
      readiness to endorse biogenetic causal explanations of mental disorder and their
      desire for social distance from people with mental disorders. The aim of this
      study is to examine why this may be the case. METHOD: In the spring of 2001, a
      population survey was carried out among German citizens aged 18 years and older,
      living in private households. A total of 5025 interviews were conducted,
      reflecting a response rate of 65.1%. At the beginning of the personal, fully
      structured interview, respondents were presented with a vignette containing a
      diagnostically unlabelled psychiatric case history, either depicting a case of
      schizophrenia or major depressive disorder. Using five-point Likert scales,
      causal attributions as well as perceived dangerousness, fear and the desire for
      social distance were assessed. RESULTS: The more respondents endorse a brain
      disease as a cause, the more dangerous they believe the person with schizophrenia
      or major depression to be. Respondents who perceive the individual in the
      vignette as being dangerous express a higher degree of fear and a greater
      preference for social distance from these individuals. As compared with brain
      disease, the relationships between heredity and perceived dangerousness are less
      pronounced for both disorders. CONCLUSIONS: Our analysis showed that endorsing
      biogenetic explanations decreases the likelihood of social acceptance of people
      with schizophrenia and major depression. Rejecting behavioural responses in the
      form of social distance desired from people with schizophrenia and major
      depression result from cognitive emotional processes in which biogenetic causal
      attributions are linked to lack of self-control, unpredictability and
      dangerousness, which, in turn, are associated with fear of these people.

PMID- 16615249
TI  - The Vietnamese version of the Self Reporting Questionnaire 20 (SRQ-20) in
      detecting mental disorders in rural Vietnam: a validation study.
AB  - BACKGROUND: There is a need to develop instruments to measure mental disorders in
      developing countries because mental disorders are increasingly being recognised
      as a major public health problem. There has been no previous study in Vietnam
      validating screening instruments for mental health problems. AIM: To adapt and to
      validate the Self Reporting Questionnaire-20 (SRQ-20) in the Vietnamese
      community. METHODS: A Vietnamese version of the SRQ-20 was developed and tested
      in 52 persons in a district hospital sample and 485 persons in a community
      sample. The psychiatrists' diagnoses were taken as the validity criterion.
      Receiver Operating Characteristic (ROC) analysis was performed to identify the
      optimal cut-off value. The area under the ROC curve (AUC) was calculated to
      assess the performance of SRQ in different sociodemographic groups. RESULTS: In
      the district hospital sample, the optimal cut-off score was 5/6 with a
      sensitivity of 85%, a specificity of 46% and an AUC of 0.74 (95% CI: 0.59-0.89).
      In the community sample, it was 6/7 with a sensitivity of 85%, a specificity of
      61% and AUC of 0.86 (95% CI: 0.81-0.93). In terms of AUC, SRQ performed
      significantly better in the age group 18-24 years as compared with other ages and
      with single persons as compared with widowed or divorced people. CONCLUSION: The
      SRQ-20 was found feasible to use and adapt to the Vietnamese setting. We
      confirmed the value of this instrument for use in developing countries, but the
      optimal cut-off limit has to be assessed and determined according to local
      conditions.

PMID- 16615250
TI  - Exploring triangulation in infancy: two contrasted cases.
AB  - Two contrasted father-mother-infant interactions are observed longitudinally
      during trilogue play. They illustrate the contribution of recent research to the
      exploration of triangulation in infancy: namely, the infant's capacity to handle
      triangular interactions and share her affects with her two parents, and the way
      that this capacity is recruited in functional versus problematic alliances. It is
      likely that an infant under stress when interacting with one parent will protest
      at that parent and also at the other. Such is the case when, for example, the
      father acts intrusively while playing with his baby. The infant is then driven to
      avert and turns to the mother. The regulation of this dyadic intrusion-avoidance
      pattern at family level depends on the family alliance. When coparenting is
      supportive, the mother validates the infant's bid for help without interfering
      with the father. Thus, the problematic pattern is contained in the dyad, and the
      infant's triangular capacities remain in the service of her own developmental
      goals. But when coparenting is hostile-competitive, the mother ignores the
      infant's bid or engages with her in a way that interferes with her play with her
      father. In this case, the infant's triangular capacities are used to relieve the
      tension between the parents. The importance of tracing family process back to
      infancy for family therapy is discussed.

PMID- 16615251
TI  - Father responsivity: couple processes and the coconstruction of fatherhood.
AB  - Forty in-depth interviews of heterosexual parents of children 5 five years of age
      and younger are analyzed using a qualitative grounded theory approach to
      understand how couples coproduce fatherhood within their day-to-day relationships
      and in social, cultural, and economic contexts. The analysis identifies the
      construct "responsivity" as a central process through which, to varying degrees,
      fathers are aware of the needs of their wives and children and able to take an
      active part in meeting them. Three groups of fathers are examined according to
      their level of responsivity: low, moderate, and high. Factors influencing degree
      of father responsivity include gender constructions, power and the wife's
      influence, attunement, work schedules, and emotional tradeoffs. Implications for
      practice are suggested.

PMID- 16615252
TI  - Family narrative interaction and children's sense of self.
AB  - Family narratives about the shared past may be a particularly significant site
      for preadolescents' emerging sense of self both as an individual and as a member
      of a unified family. We examined the relations between family narrative
      interaction style when reminiscing and preadolescents' sense of self. Results
      indicated three narrative interaction styles that describe the extent to which
      families discuss or fail to discuss their past in integrated and validating ways.
      Specifically, conversations with a coordinated perspective incorporated
      information from all members and were related to higher self-esteem, especially
      in girls. Conversations with an individual perspective, in which family members
      took turns telling their thoughts and feelings about the event without
      integration among the perspectives, were associated with a more external locus of
      control, especially in boys. Conversations with an imposed perspective, in which
      one family member was in charge of the conversation or in which unpleasant
      exchanges between members occurred, were not associated with either self-esteem
      or locus of control. Implications of these narrative interaction styles for
      children's developing sense of self are discussed.

PMID- 16615253
TI  - Using a metaperspective to clarify the structural-narrative debate in family
      therapy.
AB  - The debate in family therapy between structural and narrative therapists often
      seems irreconcilable. Drawing from work in theoretical sociology that identifies
      the basic structure of existing social theory, a metaperspective is introduced to
      clarify a discussion between leading figures in the debate. Disparate views of
      family interactions are examined in terms of more fundamental disagreements about
      the center of attention in therapy. Narrative and structural modes of
      presentation are examined as separate traditions that could not be further apart
      conceptually. Efforts to identify common ground are discussed in terms of more
      significant differences that are minimized by drawing out similarities. This
      analysis provides a framework for standing outside entrenched arguments to see
      more clearly the unique contributions of each approach.

PMID- 16615254
TI  - Acculturation, parent-adolescent conflict, and adolescent adjustment in Mexican
      American families.
AB  - We tested an acculturation model in a community sample of Mexican American
      families (146 mothers, 137 fathers, and 146 adolescents) that proposed that
      differences between parents and adolescents in acculturation would be associated
      with parent-adolescent conflict and adolescent adjustment problems. Contrary to
      hypotheses, we found that families who exhibited an acculturation gap were not
      more likely to report parent-adolescent conflict or adolescent adjustment
      problems. In fact, familial conflict and adolescent sexual experience were
      associated with high levels of acculturation among adolescents and their parents.
      Pending replication, these findings suggest that both parent and children
      acculturation may independently predict familial processes and youth outcomes,
      irrespective of an acculturation gap. Future research should consider other
      factors aside from acculturation differences that might account for parent
      adolescent conflict and adolescent adjustment in Mexican American families.

PMID- 16615255
TI  - Recruitment of first-generation Latinos in a rural community: the essential
      nature of personal contact.
AB  - The purpose of this article is to report on the success of various recruitment
      activities for a behavioral observation study with Spanish-speaking Latino
      families in a rural community in the western United States. Recruitment
      activities are pivotal to research to research because the enormous impact to the
      quality of the sample and, thus, the quality of the answers to the questions
      posed by the research. Recruitment can be especially challenging for researchers
      working with ethnic minorities due to a historical legacy of mistreatment by
      researchers that has led to healthy reticence to participate in research
      investigations. The present research presented unique challenges in that the data
      collection (1) took place in a rural community, (2) sought participation of a
      recent immigrant population, and (3) required videotaping. Data were collected
      from 50 families in a western rural community. After multiple recruitment
      strategies were used, the research team learned that word of mouth and use of
      existing community resources were the most powerful recruitment strategies.
      However, participant reports suggest that the other recruitment strategies helped
      familiarize participants with the study and potentially strengthened the
      influence of word of mouth referrals. Important differences were found between
      the easy-to-recruit and the hard-to-recruit samples within this study that
      support engagement in multiple recruitment strategies.

PMID- 16615256
TI  - Complex love as relational nurturing: an integrating ultramodern concept.
AB  - This article is based on the description of therapy with a family in which three
      members had been given a serious psychiatric diagnosis: a schizophrenic disorder,
      a borderline personality disorder, and an antisocial personality disorder. The
      underlying hypothesis was that these disorders were related to the specific ways
      in which the obstruction of relational nurturing had influenced the turbulent
      history of the family. The therapy aimed to reopen channels of nurturing
      behavior, promoting a reparative attitude on the part of the father that could be
      extended and developed throughout the relational network. This entailed working
      with concepts such as "reconfirmation" and the "relational incubator." The idea
      that the relational roots of psychopathology (which do not deny the importance of
      biological bases) are to be found in the obstruction of love by power is proposed
      as an ultramodern premise capable of integrating both modernist and postmodern
      concepts and sensibilities.

PMID- 16615257
TI  - On wisdom.
AB  - This article explores some of the features involved in making wise decisions in
      couples and family therapy. Delineating what qualities are involved in making
      wise decisions in life--so as to live the "good life" in the polis, and the
      necessary contributions of life experiences in this task--was first discussed by
      Aristotle. A major problem that therapists face today is that our society offers
      many different ways of living well--or for that matter, badly--and our theories
      do the same. Family therapy theories are not value free. I clarify that different
      family theories embody different values: clear boundaries, good attachments, the
      ability to communicate, and so on. If our theories foster certain values, then,
      as Isaiah Berlin has made clear, seeking to achieve a particular value leads to
      placing less value on another. The article concludes with some thoughts about
      values that therapists could appropriately follow in their work.

PMID- 16615258
TI  - BPGs in cardiovascular nursing care--redundant, replication, or an important step
      for nursing practice?

PMID- 16615259
TI  - Women's descriptions of coping with stress at the time of and after a myocardial
      infarction: a phenomenographic analysis.
AB  - BACKGROUND: Few studies have focused on how women are coping with myocardial
      infarction. AIM: The aim of this study was to describe and explore how women cope
      with stress at the time of and after an MI. DESIGN AND METHODS: A descriptive
      qualitative design using phenomenography was chosen. Twenty women were
      interviewed while in hospital, 14 of whom were interviewed on a second occasion
      at four, six or 10 months after the MI. FINDINGS: Cogitative actions, social
      belonging and emotional diversion were identified as a way of managing stress at
      the time of and after the MI. CONCLUSION: The present study has a comprehensive
      perspective, as the women involved described in their own words how they used
      different coping strategies to manage stress in their personal and professional
      lives related to MI. The women received help and support from the family and also
      from the health care, but they also used their own resources to reduce the
      stress.

PMID- 16615260
TI  - Influential factors for self-care in ambulatory care heart failure patients: a
      qualitative perspective.
AB  - Chronic heart failure is associated with debilitating symptoms, diminished
      quality of life and frequent hospitalizations. The literature suggests that
      effective everyday self-care decision-making can improve heart failure outcomes.
      This article focuses on the qualitative portion of a study of self-care decision
      making in community-dwelling individuals attending a heart failure clinic. Semi
      structured interviews conducted with 11 participants identified influences that
      enhance or impede self-care practices and their behavioural responses to them.
      Content analysis was used to examine predisposing attributes and enabling
      circumstances described in Connelly's Model of Self-Care in Chronic Illness.
      These interactive factors were either facilitators or barriers to self-care. The
      importance of individualizing patient teaching plans and frequent monitoring of
      factors likely to facilitate self-care were pivotal nursing implications that
      emerged from this study.

PMID- 16615261
TI  - Change in practice patterns in the management of diabetic cardiac surgery
      patients.
AB  - Diabetes and elevated blood glucose (BG) levels > 11.1 mmol/L in the acute post
      operative period have been identified as risk factors for surgical site
      infections (SSI) and nosocomial infections (Furnary, Zerr, Grunkemeir, & Starr,
      1999; American College of Endocrinology consensus guidelines for glycemic
      control, 2002). Some studies have suggested that intensive insulin therapy
      reduced in-hospital mortality and that a continuous insulin infusion should be a
      standard of care for diabetic cardiac surgery patients (Furnary et al., 2003;
      Brown & Dodek, 2001). Our urban tertiary care teaching hospital initiated an
      insulin nomogram in the intensive care unit intending to more effectively control
      blood glucose (BG) levels in cardiac surgical patients. This cohort study
      compared glucose control and clinical outcomes in 53 diabetic cardiac surgery
      patients prior to the initiation of the insulin infusion and 50 patients
      following the implementation between October 2002 and April 2003. Results
      demonstrated target glucose control in the ICU was improved by 20% (p < .001) and
      mean BG was lower in the intervention group (p < .001). However, target glucose
      (6.1-10.0 mmol/L) was exceeded in 45% of patients in the intervention group, 65%
      in the control group as well as 42% of patients on the ward. The insulin nomogram
      is now initiated as soon as the BG is obtained immediately following patient
      transfer from the operating room (OR). There is more aggressive use of sliding
      scale insulin, and earlier resumption of pre-operative diabetic regimens on the
      ward.

PMID- 16615262
TI  - Device therapy in the treatment of heart failure.

PMID- 16615263
TI  - [Future of scientific research on preventive medicine in Korea].
AB  - The Korean Society of Preventive Medicine has undergone continuous development,
      after overcoming the difficult early years, in the 59 years since its
      establishment in 1947. It has repeatedly upgraded its quality and quantity of
      research with the first journal edition in 1968 and the continuous increase in
      publication numbers, scientific articles, joint research projects, intra-field
      exchanges and participation in various international scientific activities. In
      the future, we should gather a more extensive collection of opinions regarding
      the introduction of clinical preventive medicine specialists and prepare for the
      establishment of a training program for clinical specialists into a preventive
      medicine residency course. Moreover, we should raise interest in the importance
      of protecting individual information and maintaining medicine ethics. It's
      impossible to develop academic activities without cooperation. We need such
      cooperation with basic medical approaches across a wide range of fields.
      Furthermore, we should strengthen our cooperation with aspects of clinical and
      drug epidemiology in many fields including public health, statistics, and
      dietetics. Finally, we should raise the level of international cooperation with
      many countries, including North Korea, to prevent diseases and promote health.
      Preventive medicine is a science in which practice is as important as theory. We
      must aim to nurture preventive medicine specialists who practice in many areas of
      society with the goal of preventing diseases, promoting health, improving
      fertility, and securing healthy elderly life for individuals and the entire
      population. To this end, we will endeavor to promote both theoretical and
      practical components of academic development.

PMID- 16615264
TI  - [Reformation of residency trainingship for the future of preventive medicine in
      Korea].
AB  - From the start of the residency trainingship in 1963, the residency training
      programs have been contributed much on the establishment and development of
      preventive medicine in Korea. But these programs are now have several problems to
      update the changes in health service needs of the population that were caused by
      a rapid epidemiologic transition from the acute infectious diseases to chronic
      diseases in last a few decades. Strengthening in medical practice, not just in
      knowledge is urgently required. Must have more concentrate on preventive service
      for the individual, as in clinical preventive medicine. Training residents by the
      systematic and well scheduled programs, not just 'teacher's assistant' in the
      academic facilities. Trying the change in the system of Specilty of Preventive
      Medicine to the well established several subspecialty, so more specific
      competency can be gained through the training. These approach and reformation may
      not only contribute for the better future of the preventive medicine, but also
      improve in disease prevention and health promotion, which required by the society
      in Korea.

PMID- 16615265
TI  - [Socioeconomic mortality inequality in Korea: mortality follow-up of the 1998
      National Health and Nutrition Examination Survey (NHANES) data].
AB  - OBJECTIVES: This study was conducted to examine the relationships of the several
      socioeconomic position indicators with the mortality risk in a representative
      longitudinal study of South Korea. METHODS: The 1998 National Health and
      Nutrition Examination Survey was conducted on a cross-sectional probability
      sample of South Korean households, and it contained unique 13-digit personal
      identification numbers that were linked to the data on mortality from the
      National Statistical Office of Korea. Of 5,607 males and females, 264 died
      between 1999 and 2003. Cox's regression was used to estimate the relative risks
      (RR) and their 95% confidence intervals (CI) of mortality. RESULTS: Socioeconomic
      differences in mortality were observed after adjustments were made for gender and
      age. Compared with those people having college or higher education, those people
      without any formal education had a greater mortality risk (RR = 2.21, 95% CI =
      1.12-4.40). The mortality risk among manual workers was significantly greater
      than that for the non-manual workers (RR = 2.73, 95% CI = 1.47-5.06). A non
      standard employment status was also associated with an increase in mortality:
      temporary or daily workers had a greater mortality risk than did the full-time
      workers (RR = 3.01, 95% CI = 1.50-6.03). The mortality risk for the low
      occupational class was 3.06 times greater than that of the high and middle
      occupational classes (95% Cl = 1.75-5.36). In addition, graded mortality
      differences according to equivalized monthly household income were found. A
      reduction of monthly household income by 500 thousand Korean Won (about 400 US
      dollars) was related with a 20% excess risk of mortality. Self-reported poor
      living standards were also associated with an increased risk of mortality. Those
      without health insurance had a 3.63 times greater risk of mortality than the
      insured (95% CI = 1.61-8.19). CONCLUSIONS: This study showed the socioeconomic
      differentials in mortality in a national longitudinal study of South Korea. The
      existence of socioeconomic mortality inequalities requires increased social
      discussion on social policies in Korean society. Furthermore, the mechanisms for
      the socioeconomic inequalities of mortality need to be explored in future
      studies.

PMID- 16615266
TI  - [Smoking and colorectal cancer risk in the Korean elderly].
AB  - OBJECTIVES: The incidence of colorectal cancer increased greatly among the
      elderly in Korea, but the relationship between smoking and colon cancer remains
      controversial. Few studies have targeted Asian elderly people. We analyzed the
      smoking status, the amount smoked, and the smoking duration as risk factors of
      colorectal cancer to determine their association and causality. METHODS: The
      cohort members (n = 14,103) consisted of 4,694 males and 9,409 females, and they
      were derived from the Korea Elderly Phamacepidemilogic Cohort (KEPEC), which was
      a population-based dynamic cohort. They were aged 65 years or more and they lived
      in Busan Metropolitan City between from 1993-1998; they were beneficiaries of the
      Korean Medical Insurance Corporation (KMIC). The baseline information was
      surveyed by a self-administered mailed questionnaire; after 8.7 person-years of
      mean follow up period, 100 cases of colorectal cancer occurred. The adjusted
      relative ratio (aRR) of smoking status, the smoking amount and the smoking
      duration were calculated from the Cox's proportional hazard model with the never
      smokers as a reference group and the Cox model controlled for age, gender,
      precancerous lesions of CRC, medication history of NSAIDs and antibiotics, the
      alcohol drinking status and BMI. RESULTS: Compared with the never smokers, the
      aRRs were 2.03 (95% CI = 1.02-4.03) and 1.36 (95% CI = 0.80-2.32) for the ex
      smokers and current smokers, respectively. Statistical significant trends were
      not observed for the dose-relationship among the elderly, either for the mean
      daily amount smoked (p for trend = 0.28) or for the total amount (p for trend =
      0.15). Still, the aRRs were 1.51 (95% Cl = 0.97-2.34) for the elderly who smoked
      less than 40 years and 2.35 (95% CI = 1.16-4.74) for the elderly who had 40 years
      or more of smoking (p for trend = 0.06). Smokers who started smoking before the
      age 20 had an increased aRR of 2.15 (95% CI = 1.17-3.93) compared to the never
      smokers. CONCLUSIONS: After controlling for age, gender, precancerous lesion of
      CRC, medication history of NSAIDs and antibiotics, the alcohol drinking status
      and BMI, smoking increases the risk of colorectal cancer among elderly people.
      The age when starting smoking is also important.

PMID- 16615267
TI  - [Effects of oxidative DNA damage and genetic polymorphism of the glutathione
      peroxidase 1 (GPX1) and 8-oxoguanine glycosylase 1 (hOGG1) on lung cancer].
AB  - OBJECTIVES: Oxidative DNA damage is a known risk factor of lung cancer. The
      glutathione peroxidase (GPX) antioxidant enzyme that reduces hydrogen peroxide
      and lipid peroxides plays a significant role in protecting cells from the
      oxidative stress induced by reactive oxygen species. The aim of this case-control
      study was to investigate effects of oxidative stress and genetic polymorphisms of
      the GPX1 genes and the interaction between them in the carcinogenesis of lung
      cancer. METHODS: Two hundreds patients with lung cancer and 200 age- and sex
      matched controls were enrolled in this study. Every subject was asked to complete
      a questionnaire concerning their smoking habits and their environmental exposure
      to PAHs. The genotypes of the GPX1 and 8-oxoguanine glycosylase 1 (hOGG1) genes
      were examined and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2
      naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) were measured. RESULTS: Cigarette
      smoking was a significant risk factor for lung cancer. The levels of urinary 8-OH
      dG were higher in the patients (p < 0.001), whereas the urinary 1-OHP and 2
      naphthol levels were higher in the controls. The GPX1 codon 198 polymorphism was
      associated with an increased risk of lung cancer. Individuals carrying the
      Pro/Leu or Leu/Leu genotype of GPX1 were at a higher risk for lung cancer
      (adjusted OR = 2.29). In addition, these individuals were shown to have high
      urinary 8-OH-dG concentrations compared to the individuals with the GPX1 Pro/Pro
      genotype. On the other hand, the polymorphism of the hOGG1 gene did not affect
      the lung cancer risk and the oxidative DNA damage. CONCLUSIONS: These results
      lead to a conclusion that individuals with the GPX1 Pro/Leu or Leu/Leu genotype
      would be more susceptible to the lung cancer induced by oxidative stress than
      those individuals with the Pro/Pro genotype.

PMID- 16615268
TI  - [Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and N-acetyltransferase 2
      polymorphisms and the risk of gastric cancer].
AB  - OBJECTIVES: Polymorphisms of genes from glutathione S-transferases (GSTs) and N
      acetyltransferase 2 (NAT2) have been associated with increased susceptibility to
      various cancers. Previous results showed that East Asians such as Koreans,
      Japanese and Chinese have a much higher frequency of the GSTM1 and GSTT1 null
      genotypes and NAT2 rapid acetylator type. Therefore, we investigated the
      association between the polymorphic types of GSTs (GSTM1, GSTT1, GSTP1) and NAT2
      and the incidence of gastric cancer which is one of the most prevalent cancers
      among the East Asians. METHODS: It was performed in a case-control study
      consisting of 238 healthy subjects and 108 cancer patients (54 distal and 54
      proximal carcinomas). We also evaluated the association between GSTs and NAT2 and
      the risk factors for gastric cancer such as alcohol consumption, smoking, H.
      pylori infection, family history of gastric cancer, and tumor location. RESULTS:
      In our study, the percentage of cases whose hometown was rural was higher than
      those of controls (odds ratio (OR) = 2.88; 95% CI = 1.72-4.76), and the frequency
      of the lower socio-economic status increased significantly in patients (OR =
      2.53; 95% Cl = 1.59-4.02). There was no significant difference in the GST
      polymorphic types between the cases and controls. However, NAT2 rapid or
      intermediate acetylator types were frequently detected in the cases with family
      history of gastric cancer (OR = 1.92; 95% CI = 1.79-26.0). CONCLUSIONS: These
      results suggest that the hometown and socio-economic status are important
      environmental factors for gastric carcinogenesis, and NAT2 polymorphic types
      could be associated with familial gastric carcinoma.

PMID- 16615269
TI  - [Relationship of socioeconomic factors with medical utilization for lower urinary
      tract symptoms and benign prostatic hyperplasia in a South Korean community].
AB  - OBJECTIVES: We wanted to evaluate the medical underutilization for benign
      prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS) among Korean
      elderly men and we wanted to determine their associated factors. METHODS: This
      study was conducted on 239 men with LUTS and 116 men with BPH who were compatible
      with the diagnostic criteria from a total of 641 participants. These participants
      were over 50 years old and they were randomly chosen in a community-based study
      for estimating the prevalence of BPH. Using a self-reported questionnaire, we
      surveyed the sociodemographics, health status, quality of life, lower urinary
      tract symptoms, medical utilization and reasons for not seeking treatment.
      RESULTS: Only 27.6% of the men with LUTS and 31.0% of the men with BPH reported
      having visited a doctor for urinary symptoms. The reasons for not visiting a
      doctor were, in order of responses from the group with LUTS: 'considered the
      symptoms as a part of the normal ageing process', 'not enough time to visit a
      doctor', 'financial difficulty' and 'the symptoms were not severe or bothersome'.
      Regarding BPH, the responses were the same as those of the group with LUTS
      however, 'financial difficulty' placed second. Among the men with experience of
      visiting a doctor for urinary symptoms, 33.3% of those with LUTS and 28.1% of
      those with BPH were not treated. The most common reason in both groups was 'the
      symptoms were not severe to be treated'. On a multiple logistic regression
      analysis, the larger size household (odds ratio (OR) 3.03, 95% confidence
      interval (Cl) = 1.40-6.54) and an unsatisfactory quality of life related with
      urinary symptoms (OR 2.98, 95% CI = 1.23-7.21) were associated with medical
      utilization in the group of LUTS. For BPH, the current employment status was
      related with the medical utilization (OR 2.80, 95% CI = 1.10-7.11), in addition
      to the larger size household (OR 3.24, 95% CI = 1.14-9.21). CONCLUSIONS: Many men
      with urinary symptoms do not visit a doctor. This medical underutilization for
      people with LUTS and BPH may be associated with economic status in Korea.

PMID- 16615270
TI  - [Estimating the cost savings due to the effect of Kremezin in delaying the
      initiation of dialysis treatments among patients with chronic renal failure].
AB  - OBJECTIVES: We wanted to evaluate the economic value of a pharmaceutical product,
      Kremezin, for treating patients with chronic renal failure (CRF) by estimating
      the amount of cost savings due to its effect for delaying the initiation of
      dialysis treatments. METHODS: We defined a conventional treatment for CRF
      accompanied by Kremezin therapy as 'the treatment group' and only conventional
      treatment as 'the alternative group.' The types of costs included were direct
      medical and non-medical costs and costs of productivity loss. The information on
      the effect of Kremezin was obtained from the results of earlier clinical studies.
      Cost information was derived from the administrative data for 20 hemodialysis and
      20 peritoneal dialysis patients from one tertiary care hospital, and also from
      the administrative data of 10 hemodialysis patients from one free-standing
      dialysis center. Per-capita cost savings resulting from Kremezin therapy were
      separately estimated for the cases with delay for the onset of hemodialysis and
      the cases with immediate performance of peritoneal dialysis. By computing the
      weighted average for the cases of hemodialysis and peritoneal dialysis, the
      expected per-capita cost savings of a patient with CRF was obtained. Using a
      discount rate of 5%, future cost savings were converted to the present value.
      RESULTS: The present value of cumulative cost savings per patient with CRF from
      the societal perspective would be 18,555,000-29,410,000 Won or 72,104,000
      112,523,000 Won if Kremezin delays the initiation of dialysis by 1 or 4 years.
      CONCLUSIONS: The estimated amount of cost savings resulting from treating CRF
      patients with Kremezin confirms that its effect for delaying the onset of
      dialysis treatments has a considerable economic value.

PMID- 16615271
TI  - [Effects of the personal stereo system on hearing in adolescents].
AB  - OBJECTIVES: This study was conducted to evaluate the effects of the personal
      stereo system on the hearing in adolescents. METHODS: A total of 68 adolescents
      (age: 13-18 years) who visited the ENT Department at a University Hospital in
      Daegu were personally interviewed. The questionnaires were about general
      characteristics of the subjects, the time of personal stereo system use (year,
      hour) and place. Cumulative exposure to the personal stereo system was calculated
      by the product of the total years and the daily hours of their use. Pure tone
      audiometry was performed and the hearing threshold was measured at 500, 1000,
      2000, 4000 and 8000 Hz. RESULTS: The average time of using a personal stereo
      system a day was about 3 hours and 75% of the subjects used a personal stereo
      system for 2-5 years. The elevation of threshold was more prominent in the
      subjects who used personal stereo systems for 4 years and more compared with
      those subjects who used them for 3 years and under. The elevation of hearing
      threshold was also more prominent in the subjects who used personal stereo
      systems for 4 hours and more a day compared with those subjects who used personal
      stereo systems for 3 hours and under a day. The elevation of hearing threshold
      was more prominent in the subjects who used personal stereo systems for 13 hour x
      years and more compared to the subjects who used them 12 hour x years and under.
      CONCLUSIONS: These results suggest that the elevation of hearing threshold can
      happen to adolescents who used personal stereo systems for a long time. In order
      to prevent hearing loss, we need to teach adolescents appropriate usage of the
      personal stereo system and hearing tests should be included in the periodic
      school-based physical examination for the adolescents.

PMID- 16615272
TI  - [Evaluation of Fourier transform near-infrared spectrometer for determination of
      oxalate in standard urinary solution].
AB  - OBJECTIVES: The determination of oxalate in urine is required for the diagnosis
      and treatment of primary hyperoxaluria, idiopathic stone disease and various
      intestinal diseases. We examined the possibility of using Fourier transform near
      infrared (FT-NIR) spectroscopy analysis to quantitate urinary oxalate. The
      practical advantages of this method include ease of the sample preparation and
      operation technique, the absence of sample pre-treatments, rapid determination
      and non-invasiveness. METHODS: The range of oxalate concentration in standard
      urine solutions was 0-221 mg/l. These 80 different samples were scanned in the
      region of 780-1,300 nm with a 0.5 nm data interval by a Spectrum One NTS FT-NIR
      spectrometer. PCR, PLSR and MLR regression models were used to calculate and
      evaluate the calibration equation. RESULTS: The PCR and PLSR calibration models
      were obtained from the spectral data and they are exactly same. The standard
      error of estimation (SEE) and the % variance were 10.34 mg/l and 97.86%,
      respectively. After full cross validation of this model, the standard error of
      estimation was 5.278 mg/l, which was much smaller than that of the pre
      validation. Furthermore, the MCC (multiple correlation coefficient) was 0.998,
      which was compatible with the 0.923 or 0.999 obtained from the previous enzymatic
      methods. CONCLUSIONS: These results showed that FT-NIR spectroscopy can be used
      for rapid determination of the concentration of oxalate in human urine samples.

PMID- 16615273
TI  - [Influencing factors that affect the biological monitoring of workers exposed to
      N,N-dimethylformamide in textile coating factories].
AB  - OBJECTIVES: The objective of this study is to assess the factors influencing
      biological monitoring of textile coating factory workers exposed to N,N
      dimethylformamide (DMF). METHODS: We studied 35 workers who were occupationally
      exposed to DMF from 9 textile coating factories. The study was carried out in two
      phases; summer and winter. While air concentration of DMF, temperature and
      humidity were assessed in order to monitor the atmospheric conditions, biological
      monitoring was done to determine the internal dose by analyzing the N
      methylformamide (NMF) collected from urine at the beginning and end of the shift.
      Questionnaires and medical surveillance were also obtained during the two phases.
      RESULTS: Median air concentrations of DMF in winter and summer were 1.85 ppm and
      2.78 ppm respectively. Also the difference between the urinary NMF concentration
      at the beginning and end of the shift (delta NMF) was always significant in each
      season (P < 0.001). The correlations between log DMF in air, log end-of-shift
      urinary NMF (r = 0.555, P < 0.001) and log delta NMF (r = 0.444, P < 0.001) was
      statistically significant in summer. The temperature, humidity, a shift system
      and different styles of clothing worn were significantly different during the two
      phases. In a multivariate analysis, temperature and the concentration of DMF in
      the air were the main factors influencing biological monitoring of textile
      coating factory workers. CONCLUSIONS: Concerning more comprehensive prevention
      measures to reduce exposure for those workers occupationally exposed to DMF,
      dermal exposure conditions such as temperature and humidity together with the air
      concentration of DMF should be assessed and biological monitoring is necessary to
      reduce adverse health effects, especially during the summer.

PMID- 16615274
TI  - [Association analysis of the essential hypertension susceptibility genes in
      adolescents: Kangwha study].
AB  - OBJECTIVES: In this study we examined the association between the genetic markers
      ACE (A-240T, C-93T, I/D, A2350G), AGT (M235T), AT1R (A1166C), CYP11B2 (T-344C,
      V386A), REN (G2646A), ADRB2 (G46A, C79G, T-47C, T164I), GNB3 (C825T) and ADD1
      (G460W) and the presence of essential hypertension in adolescents. METHODS: The
      Kangwha Study is an 18-year prospective study that is aimed at elucidating the
      determinants of the blood pressure level from childhood to early adulthood. For
      this study, we constructed a case-control dataset of size of 277 and 40 family
      trios data from the Kangwha Study. For this purpose, we perform a single locus
      based case-control association study and a single locus-based TDT
      (transmission/disequilibrium test) study. RESULTS: In the case-control study, the
      single locus-based association study indicated that the ADD1 (G460W) (p =
      0.0403), AGT (M235T) (p = 0.0002), and REN (G2646A) (p = 0.0101) markers were
      significantly associated with the risk of hypertension. These results were not
      confirmed on the TDT study. This study showed that genetic polymorphisms of the
      ADD1, AGT and REN genes might be related to the hypertension in Korean
      adolescents. CONCLUSIONS: This study provided useful information on genetics
      markers related to blood pressure. Further study will be needed to confirm the
      effect of the alpha adducin gene, the angiotensinogen gene and the renin gene on
      essential hypertension.

PMID- 16615275
TI  - Enhanced expression of halp gene confers cellular resistance to H2O2 induced
      senescence.
AB  - OBJECTIVE: To investigate the H2O2-induced expression of human histone
      acetyltransferase-like protein (hALP), a telomerase regulation-associated gene,
      and its effects on the stress-triggered cellular senescence. METHODS: The induced
      expression of hALP was measured by semi-quantitative RT-PCR and immunofluorescent
      histochemistry after treatment of HeLa cells by H2O2. The effects of hALP
      expression on cellular responses to H2O2 were analyzed by MTT, flowcytometry, and
      SA-beta-gal staining, respectively. RESULTS: hALP mRNA could be dose-dependently
      induced by treatments of 0.2-1.6 mmol/L H2O2, and the induction could be observed
      after 6 hours and kept for 36 hours in the presence of 0.4 mmol/L H2O2.
      Meanwhile, the immunofluorescent staining showed marked stronger nuclear
      intensity of hALP protein in H2O2-treated HeLa cells. In the treatment of H2O2,
      the ectopic expression of hALP enhanced continuous growth and overcame G2/M
      arrest as well as decreased senescence-associated beta-gal staining. On the
      contrary, the transfected clones with antisense or blank vector and original He
      La cells presented growth suppression, G2/M delay and higher percentage of SA
      beta-gal activities in the presence of H2O2. CONCLUSIONS: The expression of hALP
      could be up-regulated by treatment of H2O2, and elevated expression could enhance
      cellular resistance to H2O2-induced cellular senescence. The data might be of
      references to elucidation of basic biological function of hALP gene and its
      associated telomerase activity.

PMID- 16615276
TI  - Hepatocyte growth factor protects against apoptosis induced by advanced glycation
      end products in endothelial cells.
AB  - OBJECTIVE: To investigate the effects of hepatocyte growth factor (HGF) on
      vascular endothelial cells apoptosis induced by advanced glycation end products
      (AGEs) and its possible mechanism. METHODS: Human umbilical vein endothelial
      cells (HUVECs) were cultured in vitro and intervened by different concentrations
      of AGEs and HGF. The cell inhibitory rates of each group with different culture
      time (12, 24, 48, and 72 hours) were measured by methyl thiazolyl tetrazolium
      (MTT) assay. The early stage apoptosis was detected by flow cytometry with
      Annexin V-FITC/PI double staining, morphology of cell apoptosis was observed by
      hoechst 33258 fluorescence staining, and the expression of apoptosis-associated
      genes Bax and Bcl-2 were determined by Western blotting. The activity of caspase
      3 was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Morphological observation indicated that high concentration of AGEs induced
      characteristic apoptotic changes in HUVECs. Within a certain concentration range,
      HUVECs apoptosis inducing rates by AGEs were in both dose- and time-dependent
      manners. HGF significantly inhibited the apoptosis of HUVECs induced by AGEs (P <
      0.05). AGEs significantly promoted expression of Bax protein, but not Bcl-2.
      Whereas HGF significantly promoted the expression of Bcl-2 (P < 0.01) and
      decreased the activity of caspase-3 (P < 0.05) without affecting Bax level.
      CONCLUSIONS: AGEs can induce the apoptosis of endothelial cells in vitro. HGF may
      effectively attenuate AGEs-induced endothelial cells apoptosis through
      upregulating Bcl-2 gene expression and inhibiting caspase-3 activation.

PMID- 16615277
TI  - Treatment options for patients with recurrent ovarian cancer: a review of 54
      cases.
AB  - OBJECTIVE: To evaluate the efficacy of treatment options for patients with
      recurrent ovarian cancer. METHODS: From 1990 to 2000, 54 patients with recurrent
      ovarian cancer primarily treated in Peking Union Medical College Hospital were
      selected and reviewed. All the clinical data related to the recurrent tumor were
      collected. Two-side P values for differences in survival were calculated by the
      Cox regression model. RESULTS: The platinum-free interval > 6 months and the
      surgery followed by salvage chemotherapy prolonged survival time of the patients
      with recurrent ovarian cancer (95% CI = 0.153-0.987, P = 0.047; 95% CI = 1.611
      10.914, P = 0.003, respectively). The increased number of chemotherapy cycles ( >
      10 months) offered some benefit on the survival (95% CI = 0.110-1.090, P =
      0.070). The initiation of treatment and chemotherapy regiments failed to
      demonstrate an improvement in survival. CONCLUSION: The treatment options for
      patients with recurrent ovarian cancer depend on the platinum-free-interval of
      the patients. A strategy of secondary surgical cytoreduction followed by salvage
      chemotherapy is suggested for the patients with platinum-sensitive disease.

PMID- 16615278
TI  - Drug therapy of paroxysmal atrial fibrillation in the elderly over 75 years old.
AB  - OBJECTIVE: To investigate the effectiveness and safety of various agents on
      paroxysmal atrial fibrillation in the elderly over 75 years old. METHODS: Totally
      264 in-patients (75-91 years old, 185 males and 79 females) with atrial
      fibrillation history of less than 7 days were enrolled in this study. A total of
      611 atrial fibrillation episodes were recorded, but 130 episodes (22.3%) of
      atrial fibrillation were auto-converted to sinus rhythm. The rest 481 episodes of
      atrial fibrillation were divided into six groups based on the drug used. RESULTS:
      The cardioversion ratio of atrial fibrillation were 9.5%, 46.9%, 71.7%, 55.9%,
      32.7%, and 73.6% in control, cedilanid, amiodarone, propafenone, verapamil, and
      quinidine groups, respectively. Ventricular rate control were 5.4%, 83.6%, 84.9%,
      77.9%, 78.8%, and 11.3% in those groups, respectively. The total effective rates
      of amiodarone and cedilanid groups were the highest. When the ventricular rate
      was controlled to below 90 bpm, the patients would almost complain of no
      discomfort. No severe side-effect was observed in each group. CONCLUSION:
      Amiodarone and cedilanid may be the proper drugs for the treatment of paroxysmal
      atrial fibrillation in the elderly. The above antiarrhythmics in each therapeutic
      group were relatively safe and effective.

PMID- 16615279
TI  - Fallopian tube prolapse following hysterectomy.
AB  - OBJECTIVE: To investigate the clinical diagnosis, treatment, and prevention of
      fallopian tube prolapse (FTP) after hysterectomy. METHODS: A total of 7949
      patients received hysterectomy from January 1983 to August 2005 in Peking Union
      Medical College Hospital, and 9 cases (including 1 case from other hospital) of
      FTP after hysterectomy were involved during this period. All of them were
      diagnosed according to pathological results and were followed up. The symptoms,
      diagnosis, and treatment of the FTP patients were analyzed retrospectively.
      RESULTS: The incidence of FTP after hysterectomy was 0.1% (8/7949), with the
      incidence of FTP after transabdominal hysterectomy being 0.06% (4/6229), after
      trans-vaginal hysterectomy being 0.5% (4/780), after laparoscopic assistant
      vaginal hysterectomy being 0 (0/940). There was no symptom in 3 cases. The pelvic
      examination revealed the typical prolapsed fimbrial end of a fallopian tube in 3
      cases and the other 6 cases revealed red granulation tissue. All of them were
      excised vaginally and cauterized. The results were proved by pathological
      examination. No recurrence was reported during follow-up. CONCLUSIONS: FTP is a
      rare complication after hysterectomy. The prognosis is well after proper
      diagnosis and treatment Fixation of accessories onto the pelvic wall and complete
      peritonealization at the time of hysterectomy are the most important methods to
      prevent FTP after hysterectomy.

PMID- 16615280
TI  - Missing diagnosis of neck metastases by routine detecting method in laryngeal
      carcinomas.
AB  - OBJECTIVE: To evaluate the missing diagnosis of neck metastases by routine
      detecting method (palpation combined with one pathological slide) in laryngeal
      carcinomas. METHODS: Sixty-six specimens of neck dissections were collected and
      observed by routine method, transparent method, and continuous sliding method.
      RESULTS: Totally, 1153 lymph nodes were detected by palpation method and another
      1204 lymph nodes were detected by transparent method. The lymph nodes detected by
      transparent method account for 51.1% of the total, and among them 10 metastases
      were found, which account for 15.6% (10/64) of metastatic lymph nodes. For those
      with no metastasis detected by routine method, 50 microm interval continuous
      sliding method was performed, and 14 tiny metastases were found, which account
      for 21.9% (14/64) of metastatic lymph nodes. Detecting by routine method, most
      lymph nodes (95%) were in tumor growth and tumor suffusion stage. The missing
      diagnosis rate of routine method was 37.5% (24/64). CONCLUSIONS: When routine
      method was used to detect lymph nodes in neck specimens, missing diagnosis should
      be considered to select best therapy. Through transparent method small lymph
      nodes could be found and it is a valuable method to observe pathological changes
      of small nodes. Continuous sliding method could find micrometastasis precisely,
      but the work burden is heavy and it is difficult to be widely used.

PMID- 16615281
TI  - Islet formation and regeneration.
AB  - OBJECTIVE: To explore the mechanisms of differentiation and development of
      pancreatic endocrine cells as well as pancreatic regeneration. METHODS: Human
      embryonic pancreatic tissue at 7-14 weeks of gestation was collected. Diabetes
      mellitus rat model was induced with 65 mg/kg of streptozotocin. Insulin,
      glucagon, somatostatin, nestin, and cytokeratin 19 (CK19) of pancreatic tissues
      were observed by immunohistochemistry. RESULTS: At 9 weeks of gestation,
      pancreatic epithelial cells began to co-express insulin, glucagon, somatostatin,
      and CK19 before migration. Islet cells gradually congregated along with the
      increase of aging, and at 14 weeks of gestation histological examination showed
      islet formation. At 12 weeks of gestation, nestin-positive cells could be seen in
      the pancreatic mesenchyme. During early embryogenesis, islet cells of pancreatic
      ducts co-expressed insulin, glucagon, and somatostatin. During pancreatic
      regeneration after damage, nestin expression of islet cells increased.
      CONCLUSION: In the early stage of embryogenesis, islet cells of primary
      pancreatic ducts can be differentiated to multipotential endocrine cells before
      migration. During tissue regeneration, pancreatic stem cells may differentiate
      and proliferate to form pancreatic islet.

PMID- 16615282
TI  - TGF-beta1/SMAD signaling pathway mediates p53-dependent apoptosis in hepatoma
      cell lines.
AB  - OBJECTIVE: To determine whether transforming growth factor betal (TGF-beta1)/Smad
      signaling pathway mediates p53-dependent apoptosis in hepatoma cell lines.
      METHODS: Three human hepatic carcinoma cell lines, HepG2, Huh-7, and Hep3B, were
      used in this study. TGF-beta1-induced apoptosis in hepatic carcinoma cell lines
      was analyzed using TUNEL assay. For identifying the mechanism of apoptosis
      induced by TGF-beta1, cell lines were transfected with a TGF-beta1-inducible
      luciferase reportor plasmid containing Smad4 binding elements. After
      transfection, cells were treated with TGF-beta1, then assayed for luciferase
      activity. RESULTS: The apoptosis rate of HepG2 cell lines (48.51% +/- 8.21%) was
      significantly higher than control (12.72% +/- 2.18%, P <0.05). But TGF-beta1 was
      not able to induce apoptosis of Huh-7 and Hep3B cell lines. The relative
      luciferase activity of TGF-beta1-treated HepG2 cell lines (4.38) was
      significantly higher than control (1.00, P < 0.05). But the relative luciferase
      activity of TGF-beta1-treated Huh-7 and Hep3B cell lines less increased compared
      with control. CONCLUSIONS: HepG2 cells seem to be highly susceptible to TGF-beta1
      induced apoptosis compared with Hep3B and Huh-7 cell lines. Smad4 is a central
      mediator of TGF-beta1 signaling transdution pathway. TGF-beta1/Smad signaling
      pathway might mediate p53-dependent apoptosis in hepatoma cell lines.

PMID- 16615283
TI  - Over-expression of extracellular signal-regulated kinase in vascular smooth
      muscle cell of hypertensive rats.
AB  - OBJECTIVE: To investigate whether extracellular signal-regulated kinase (ERK1/2)
      was involved in changes of vascular smooth muscle cell (VSMC) under hypertension.
      METHODS: Two-kidney one clip Wistar hypertensive rats (WHR) were sacrificed and
      their right kidneys were harvested 4 weeks after surgery. The spontaneously
      hypertensive rats (SHR) were divided into 4, 8, and 16 weeks old groups (SHR4w,
      SHR8w, and SHR16w), respectively. The control group were sham operated age
      matched Wistar rats. Immunohistochemical technique and Western blotting were
      applied to study ERK1/2 protein expression in VSMC of the renal vascular trees in
      WHR, SHR, and control rats. RESULTS: Blood pressure in two-kidney one clip WHR
      obviously increased at one week after surgery, and reached to 198. 00 +/- 33. 00
      mm Hg at the end of experiment, significantly higher than that in the control
      rats (P < 0.01). Blood pressure in SHR4w (108.00 +/- 11.25 mm Hg) was similar to
      that in the controls. However, it rose to 122.25 +/- 21.75 mm Hg in SHR8w, and
      even up to 201.75 +/- 18.00 mm Hg in SHR16w, which were significantly higher than
      that of both the SHR4w and the controls (P < 0.01). The rate and degree of
      glomerular fibrosis in WHR were significantly higher than controls (P < 0.05).
      Hyaline degeneration of the afferent arterioles was found in WHR. In contrast,
      either fibrosis of glomerulus or hyaline degeneration of the arterioles or
      protein casts was not observed in SHR4w, SHR8w, and SHR16w. Immunohistochemical
      staining results showed expression of ERK1 was similar to that of ERK2. The
      positive rates of ERK2 staining in VSMC of afferent arterioles, interlobular,
      interlobar, and arcuate arteries in two-kidney one clip WHR were significantly
      higher (7.09% +/- 1.75%, 14.57% +/- 4.58%, 29.44% +/- 7.35%, and 13.63% +/- 3.
      85%, respectively) than that of the controls(P < 0.01). The positive rates of
      ERK2 staining in VSMC at afferent arterioles, interlobular, interlobar, and
      arcuate arteries in SHR16w were significantly higher (12.09% +/- 1.40%, 24.17% +/
      6.92%, 32.44% +/- 4.05%, and 18.61% +/- 3.35%, respectively) than that of the
      controls (P < 0.01), too. The expression of ERK1/2 protein of kidney in WHR and
      SHR16w was significantly higher than that in the controls by Western blotting
      assay (P < 0.01). CONCLUSION: Extracellular signal transduction system are highly
      expressed in kidney VSMC of two-kidney one clip WHR and SHR. Phospho-ERKI/2 may
      play an important role in VSMC hypertrophy and hyperplasia under hypertension.

PMID- 16615284
TI  - Outcome of posterolateral fusion versus circumferential fusion with cage for
      lumbar stenosis and low degree lumbar spondylolisthesis.
AB  - OBJECTIVE: To evaluate the outcome of two methods for stabilization and fusion:
      posterolateral fusion and circumferential fusion involving posterior lumbar
      interbody fusion for lumbar stenosis with Grades 1 and 2 lumbar
      spondylolisthesis. METHODS: From April 1998 to April 2003, 45 patients suffering
      from lumbar stenosis with low degree lumbar spondylolisthesis treated in our
      hospital were retrospectively reviewed and assigned to two groups. Among them, 24
      patients (group A) were treated with instrumented posterolateral fusion and 21
      patients (group B) with instrumented circumferential fusion. The two groups were
      compared for clinical and radiological outcomes. RESULTS: All patients were
      followed up for 12 to 72 months. In group A, results showed preoperative clinical
      symptoms disappeared completely in 12 of 24 patients, and pain relief was seen in
      91.7% (22/24). Two cases suffered from residual symptoms. Twenty-two cases
      obtained complete reduction of olisthy vertebral bodies, and anatomical reduction
      rate was 91.7%. No infection or neurological complication occurred in this group.
      In group B, results showed preoperative clinical symptoms disappeared completely
      in 13 of 21 patients, and pain relief was seen in 90.5% (19/21). One case
      suffered from residual symptoms. Twenty cases obtained complete reduction of the
      olisthy vertebral bodies, and anatomical reduction rate was 95.2%. Four cases of
      infection or neurological complication occurred in this group. Both groups
      indicated no significant difference in clinical outcomes and anatomical reduction
      rate during follow-up. But group A had better intraoperative circumstances and
      postoperative outcome than group B, while group B had better postoperative
      parameters in X-ray of Angle of Slipping and Disc Index than group A.
      CONCLUSIONS: The first choice of surgical method for lumbar stenosis with low
      degree lumbar spondylolisthesis is instrumented posterolateral fusion. Only when
      patients suffer from severe preoperative disc degeneration and low back pain or
      intervertebral instability should we consider indications for additional use of
      CAGE.

PMID- 16615285
TI  - Corrective surgery of congenital scoliosis with type II split spinal cord
      malformation.
AB  - OBJECTIVE: To investigate the corrective results of congenital scoliosis with
      type II split spinal cord malformation. METHODS: By reviewing the medical records
      and roentgenograms of congenital scoliosis patients with type II split spinal
      cord malformation that underwent corrective surgery, septum location and length,
      curve type, coronal and sagittal Cobb's angles, apical vertebral rotation and
      translation, and trunk shift were measured and analyzed. RESULTS: A total of 23
      congenital scoliosis patients with type II split spinal cord malformation were
      studied, 6 cases were due to failure of segmentation, 8 cases due to failure of
      formation, and the remaining 9 cases due to mixed defects. The fibrous septums
      were located in the thoracic spine in 8 patients, lumbar spine in 4 patients,
      thoracic and lumbar spine in 10 patients, and from cervical to lumbar spine in 1
      patient The septum extended an average of 4.9 segments. Corrective surgeries
      included anterior correction with instrumentation in 2 patients, posterior
      correction with instrumentation in 11 patients, anterior release and posterior
      correction with instrumentation in 6 patients, anterior and posterior resection
      of the hemivertebra and posterior correction with instrumentation in 4 patients.
      The pre- and postoperative coronal Cobb's angles, apical vertebral translations,
      apical vertebral rotations, trunk shifts were 61.9 degrees and 32.5 degrees (P <
      0.001), 48.9 mm and 31.5 mm (P < 0.001), 1.2 and 1.1, 12.7 mm and 8.2 mm,
      respectively. The average correction rate of coronal Cobb's angle was 47.5%. The
      sagittal balance was also well improved. The fibrous septums were all left in
      situ. There was no neurological complication. CONCLUSION: For congenital
      scoliosis with type II split spinal cord malformation, positive correction
      results with no neurological complication may be obtained without resection of
      the fibrous septum.

PMID- 16615286
TI  - Findings of chest radiograph and spiral computed tomography in Swyer-James
      syndrome.
AB  - OBJECTIVE: To evaluate the value of X-ray and spiral computed tomography (SCT) in
      the diagnosis of Swyer-James syndrome (SJS). METHODS: A total of 28 patients, 12
      males and 16 females, were studied retrospectively. Ages ranged from 11 to 57
      years, the mean age was 32 years. All patients underwent inspiratory chest X-ray
      films, 5 with expiratory chest films and 1 with bronchogram. Furthermore,
      inspiratory and expiratory SCT scans were performed. The SCT findings were
      analyzed and compared with X-ray films. RESULTS: SCT demonstrated 56 lobes with
      hyperlucency and diminished vascularity. The size of 51 lobes were smaller and 5
      were normal. X-ray films showed that hyperlucency was only in 29 lobes, in which
      19 lobes were small-sized and the other 10 lobes normal. There were 56 lobes with
      air-trapping on expiratory SCT scans, but only 5 lobes with air-trapping on
      expiratory X-ray films. Bronchogram in 1 case demonstrated bronchiectasis and
      bronchiolitis obliterans. SCT showed 24 patients with bronchiectasis, 9 patients
      with tuberculosis, 10 patients with bronchiolitis, and 2 with segmental collapse.
      CONCLUSION: SCT scan is superior to chest radiography in the diagnosis and
      differential diagnosis of SJS.

PMID- 16615287
TI  - Changes of interleukin-6 and related factors as well as gastric intramucosal pH
      during colorectal and orthopaedic surgical procedures.
AB  - OBJECTIVE: To investigate the changes of perioperative serum levels of
      interleukin-6 (IL-6), C-reactive protein (CRP), and cortisol, as well as gastric
      intramucosal pH (pHi) and plasma lactate, aiming to compare systemic changes and
      tissue perfusion during colorectal and orthopaedic surgical procedures. METHODS:
      Twenty patients were randomly assigned to two groups, 10 cases of operation on
      vertebral canal, 10 cases of colorectal radical operation. Venous blood was drawn
      at 1 day before operation, 2, 4, and 6 hours following skin incision, and 1 day
      after operation, in order to measure serum IL-6, CRP, and cortisol. pHi and
      plasma lactate were also measured at the same time points. RESULTS: Serum
      concentrations of IL-6 and cortisol increased gradually following operation,
      reaching the peak value at 6 hours from the beginning of operation. CRP was not
      detectable until the first day after operation. Peak concentration of IL-6 had
      positive relationship with CRP. These variables changed more significantly in
      colorectal group than that in orthopaedic group (P < 0.05). pHi decreased
      gradually, reaching the lowest level at 4 hours from the beginning of operation,
      and to more extent in colorectal group than that in orthopaedic group (P < 0.05).
      CONCLUSION: IL-6 may reflect tissue damage more sensitively than CRP. Colorectal
      surgery might induce systemic disorder to more extent, in terms of immuno
      endocrinal aspect as well as tissue perfusion, reflected with pHi.

PMID- 16615288
TI  - Diagnosis, treatment, and research of etiology of spontaneous neonatal gastric
      perforation.

PMID- 16615289
TI  - Numed Cheatham-Platinum stent and balloon in balloon delivery catheter for
      treatment of native coarctation of the aorta.

PMID- 16615290
TI  - Effect of bacterial infection on proliferating cell nuclear antigen expression
      after partial splenectomy of rabbits using microwave coagulator.

PMID- 16615291
TI  - The influence of words as determinants of U.S. international and domestic health
      policy: part II.

PMID- 16615292
TI  - Testing a measure of cyberloafing.
AB  - Using a primary sample of medical technologists (MTs) and a second validation
      sample, the results of this study showed initial support for a three-factor
      measure of cyberloafing. The three scales were labeled browsing-related, non-work
      related e-mail, and interactive cyberloafing. MTs who perceived unfair treatment
      in their organization (i.e., lower organizational justice) were more likely to
      exhibit all three types of cyberloafing. MTs who did not care as much about
      punctuality and attendance (i.e., higher time abuse) were more likely to display
      browsing-related and non-work-related e-mail cyberloafing. Finally, MTs who
      perceived an inability to control their work environment (i.e., powerlessness)
      were more likely to display interactive cyberloafing. Study limitations and
      suggestions for future research are discussed.

PMID- 16615293
TI  - Certified athletic trainers' knowledge and perception of professional preparation
      involving eating disorders among athletes.
AB  - The perceived adequacy of professional preparation about eating disorders and
      disordered eating has not been evaluated in certified athletic trainers (ATCs).
      This study was intended to establish how ATCs perceive their professional
      preparation and educational background in identifying and managing eating
      disorders. A 42-item Web-based survey was specifically created for this study and
      disseminated to certified 14,477 members of the National Athletic Trainers'
      Association (NATA), of whom 13.6% (n = 1,966) responded (mean age of respondents,
      31.87 +/- 7.82 yrs). The survey consisted of an 11-question demographic section,
      13 Likert-scale statements, five "check all that apply" questions, 10 yes/no
      questions, two "fill in the best answer" questions, and one "check one that
      applies" question. Statistical analysis focused on qualitative and descriptive
      analysis of survey items. Our results suggest that ATCs believe that they do not
      receive enough professional preparation or education in dealing with eating
      disordered athletes. Despite this finding, they also believe it is their
      responsibility to identify and deal with eating disordered athletes. The overall
      findings indicate a need and desire for continuing education about eating
      disorders.

PMID- 16615294
TI  - Fostering reflective practice: self-assessment abilities of physical therapy
      students and entry-level graduates.
AB  - Adopting the American Physical Therapy Association Clinical Performance
      Instrument, physical therapy (PT) interns are required to self-assess, hence the
      need for development of self-assessment abilities. The purpose of this research
      was threefold: (1) to develop an interview guide instrument to gather qualitative
      data, (2) to investigate the experience of self-assessment of PT students and new
      graduates, and (3) to identify training needs and propose a plan to incorporate
      self-assessment for PT lifelong learners. This study evaluated the self
      assessment abilities of PT learners by investigating the following self
      assessment components: (1) abilities and skills, (2) barriers and/or support, (3)
      training needs, and (4) essential elements for development. The sample consisted
      of 11 PT learners and internal and external evaluative committee members.
      Qualitative and evaluative methods were implemented to generate data addressing
      research questions related to (1) interview instrumentation; (2) self-assessment,
      with data gathering through semistructured interviews; and (3) evaluative
      examination of the plan to incorporate self-assessment. Data were analyzed for
      emerging codes and themes, synthesized, and recontextualized. Formative and
      summative evaluative committees validated the interview guide instrument and
      proposed plan for incorporation of self-assessment. Core themes emerged
      pertaining to specific aspects of self-assessment, including requirements, areas
      for improvement, motivational and promotion factors, and activities that
      facilitate self-assessment. Participants exhibited self-assessment abilities,
      encountering obstacles and support, important to health care professionals,
      educators, and clinical faculty. Training needs were identified for PT learners
      and for clinical and academic faculty. These findings parallel with Schon's
      concept of reflective practice and Bandura's social learning theory. The self
      assessment plan includes practice improvement components viable for health
      professions education.

PMID- 16615295
TI  - Preferred teaching and testing methods of athletic training students and program
      directors and the relationship to styles.
AB  - OBJECTIVE: The purpose of this study was (1) to investigate differences between
      athletic training students' and program directors' preferences for teaching and
      testing methods and (2) to investigate the relationship between style and
      preferred teaching and testing methods using the Gregorc Style Delineator (GSD)
      and the Preferred Teaching and Testing Method Inventory (PTTMI). PARTICIPANTS: We
      cluster sampled 200 undergraduate students (100% return; 68 men, 132 women; mean
      age, 20.12 +/- 2.02 yrs) and simple random sampled 100 program directors (43%
      return; 22 men, 21 women; mean age, 40.05 +/- 9.30 yrs) from Commission on
      Accreditation of Allied Health Education Programs-accredited athletic training
      education programs. DESIGN AND MEASUREMENT: We used a correlational research
      design to compare the preferred teaching and testing methods of undergraduate
      students and program directors. All subjects completed a demographic survey, the
      GSD, and the PTTMI. Our analyses included two separate 2 (role: student and
      program director) x 8 (method: teaching or testing techniques) and two separate 4
      (style: concrete sequential, abstract sequential, abstract random, concrete
      random) x 8 (method: teaching and testing techniques) mixed-model analyses of
      variance. RESULTS: We found that athletic training students and program directors
      had significantly different preferences for teaching (p < 0.01) and testing (p <
      0.01) methods, respectively. No significant relationships were revealed between
      athletic training students' and program directors' Mind Style typologies and
      their preferences for teaching or testing method. CONCLUSIONS: We recommend that
      athletic training and allied health educators consider implementing pedagogy that
      accentuates students' styles and consider self and students' preferences for
      preferred teaching and testing methods as time and topic permit.

PMID- 16615296
TI  - Coping with a turbulent health care environment: an integrative literature
      review.
AB  - Health care employers of allied health personnel and the academic programs
      producing these professionals have had to cope with an environment of major
      changes and ongoing turbulence. To better understand the descriptions of and
      research on the health care environment in relation to strategic typologies, an
      integrative literature review was conducted. Drawing from multiple disciplines,
      the information presented offers potential models and approaches to assess and
      respond to a turbulent health care environment for both schools of allied health
      and allied health practice sites. The integrative literature review revealed that
      innovation can enhance profitability if not pursued with fragmentation of an
      organization's core identity. Prospector and analyzer approaches appear to offer
      greater viability in a turbulent health care environment than reactor or defender
      types. Differentiation of services can be pursued to produce a unique reputation
      for a health care organization.

PMID- 16615297
TI  - Interrater reliability among athletic training site visitors.

PMID- 16615298
TI  - Genetic, phenotypic, metabolic and endocrine features in small for gestational
      age and very low birth weight children.

PMID- 16615299
TI  - Insulin sensitivity in people born pre-term, with low or very low birth weight
      and small for gestational age.
AB  - Evidence has accumulated that small for gestational age (SGA) children have long
      term adult health consequences including obesity, Type 2 diabetes mellitus,
      hypertension, coronary artery disease and stroke. This increased risk of later
      adult disease is likely a consequence of an early, persistent reduction in
      insulin sensitivity. The SGA children and adults studied were predominantly at
      term gestation, and it appears that prematurity also leads to insulin resistance
      with possibly similar health consequences for later life. Both term SGA and
      premature children have an abnormal early environment: one in utero and one post
      natally. Parallels are made among those born SGA at term or premature to show the
      potential importance of maternal factors, the intrauterine milieu, including
      nutrient supply and intake in fetal and early newborn life. It is possible that
      manipulation of these factors during early neonatal life in premature babies
      could lead to normalisation of insulin sensitivity. To confirm this hypothesis,
      further studies are needed to better understand the pathophysiological mechanisms
      leading to reduced insulin sensitivity and confirm that prematurity is linked
      with similar long-term health consequences as being born SGA.

PMID- 16615300
TI  - Silver-Russell syndrome and its genetic origins.
AB  - Silver-Russell syndrome (SRS) is both clinically and genetically a heterogeneous
      congenital disorder. Patients are characterised by severe intrauterine and post
      natal growth retardation, dysmorphic facial features and, asymmetry. Various
      chromosome abnormalities have been associated with the disease, involving most
      often chromosome 7 and 17. In about 7% of sporadic cases, maternal uniparental
      disomy of chromosome 7 has been detected. Most recent findings suggest that
      imprinting defects within the 11p15 region also play a role in SRS.

PMID- 16615301
TI  - 'Non-Mendelian' genetics of fetal growth.
AB  - Mendelian genetics showed that a few mutated genes, or errors in parental
      imprinting, can lead to major phenotypic changes (diseases) in pre-natal growth.
      Mendelian genetics, however, do not explain the individual subtle variability of
      size at birth within the normal range. Fetal growth is a complex multifactorial,
      multigenic trait made of various sub-traits, such as body mass, fat and muscle,
      brain mass, head circumference, skeletal growth of the spine and limbs. It is
      likely that multiple genetic factors and genomic variants are responsible for the
      variations of these sub-traits. A study has been launched to investigate the
      genetics of the variation of human birth weight, with the ultimate aim of
      identifying genomic variations that are within or near certain genes and are
      associated with variations of human height and weight at birth.

PMID- 16615302
TI  - Mendelian genetic causes of the short child born small for gestational age.
AB  - About 5% of newborns are small for gestational age (SGA) and 10-15% of them do
      not naturally catch up on growth by 2 yr of age. The growth of the fetus from
      conception to birth results from complex interactions of maternal and fetal genes
      with the environment, and factors such as malnutrition are well known to
      influence fetal growth. Specific genetic disorders such as Leprechaunism, Bloom
      syndrome, Fanconi anemia are inherited, but are very rare causes of intrauterine
      growth retardation. Recent published research on the actions of IGF-I in humans
      and the phenotypes of children with genetic defects in the GH/IGF axis establish
      IGF-I signaling via its receptor (IGF-IR) as the critical growth-controlling
      element in man. The aim of this article is to review certain SGA disorders of
      Mendelian genetic origin, with an emphasis on defects in the insulin and IGF
      pathways which may be implicated in the persistence of short stature in some
      children born SGA.

PMID- 16615303
TI  - Sensitivity to IGF-I in short children born small for gestational age.
AB  - About 5% of newborns are classified as small for gestational age (SGA) and of
      these, 10-15% do not catch up in growth by 2 yr of age. In addition to genetic
      mutations in the GH-IGF-IGFBP axis, environmental factors may re-program growth
      during fetal development leading to altered hormone sensitivity. This review
      summarizes the importance of GH treatment in SGA children. Although GH dose is
      the most relevant factor for growth response in children born SGA, higher GH
      doses are needed in SGA subjects to induce a growth response comparable to GH
      deficient (GHD) patients. Therapeutic difficulties possibly arise from the
      impaired hormone sensitivity along the GH-IGF-IGFBP axis. Indeed, several
      observations point towards impaired sensitivity to hormones involved in the GH
      IGF-IGFBP axis in children born SGA. The inability to classify SGA patients
      according to the relative GH and IGF-I concentrations is probably due to the
      large variation in hormone sensitivity patterns in patients with SGA. Simple
      laboratory tests need to be established that directly quantify sensitivity to
      parameters in the GH-IGF-IGFBP axis, such as IGF-I. Adequate additional therapies
      could in future result in positive effects on co-morbidities associated with IGF
      I insensitivity in SGA children in addition to height gain.

PMID- 16615304
TI  - Arsenic uptake and accumulation in fern species growing at arsenic-contaminated
      sites of southern China: field surveys.
AB  - Aiming at searching for new arsenic (As) hyperaccumulators, field surveys were
      conducted at 12 As-contaminated sites located in Guangxi and Guangdong Provinces
      of southern China. Samples of 24 fern species belonging to 16 genera and 11
      families as well as their associated soils were collected and As concentrations
      in plant and soil samples were determined by inductively coupled plasma-atomic
      emission spectrometry (ICP-AES). The results show that among 24 fern species,
      Pteris multifida and P. oshimensis can (hyper)accumulate As in their fronds with
      high concentrations in addition to P. vittata and P. cretica var. nervosa, which
      have been previously identified as As hyperaccumulators. Total As concentrations
      in soils associated with P. multifida and P. oshimensis varied from 1262 to
      47,235 mg kg(-1), but the DTPA-extractable As concentrations were relatively low,
      with a maximum of 65 mg kg(-1). Forty-four of 49 samples of P. multifida
      collected from five sites and 3 of 13 samples of P. oshimensis collected from one
      site accumulated over 1000 mg As kg(-1) in their fronds and As concentrations in
      the fronds were higher than those in the petioles and rhizoids. Although As
      concentrations in the fronds of P. oshimensis (789 mg kg(-1) averaged, range 301
      2142 mg kg(-1)) were comparatively lower than those of P. multifida (1977 mg kg9
      1), 624-4056 mg kg(-1)), its high aboveground biomass makes it more suitable for
      phytoremediating As-contaminated soils. Among all the species in Pteris genus
      studied, Pteris semipinnata accumulated only very low As concentration in its
      fronds (8 mg kg(-1), 1-18 mg kg(-1)). Further research is needed to study the
      differences in As uptake and accumulation among fern species in the same or other
      genera.

PMID- 16615305
TI  - Uptake and exudation behavior of perchlorate in smartweed.
AB  - Perchlorate uptake has been reported in a variety of vascular plants, but the
      mechanisms affecting the uptake, translocation, and exudation of ClO4(-) in
      plants are not well known. The uptake and transport behavior of ClO4(-) was
      studied in smartweed (Polygonum spp.) grown in aerated hydroponic ClO4(-)
      solutions with or without other common anions. Uptake followed first-order
      kinetics (0.017 +/- 0.003 day(-1)) and there was no apparent competitive effect
      on ClO4(-) uptake for up to 500 mg L(-1) of NO3(-) -N, SO4(2-), PO4(3-), or Cl(
      ). The net ClO4(-) mass uptake was proportional to transpiration but with some
      exclusion of ClO4(-) from the transpiration stream. Up to 4% of the ClO4(-) in
      plants after a 30-d exposure to a 10-mg/L solution of ClO4(-) was exuded from the
      roots within 15 d after the exposure was ended. Perchlorate exudation followed
      first-order kinetics with a rate coefficient of 0.0018 +/- 0.0006 (day(-1)
      Results obtained in this study indicate that evapotranspiration may be the
      critical variable to predict accumulation potential in plants and that
      phytoremediation strategies should take into account the re-release potential of
      ClO4(-) via exudation.

PMID- 16615306
TI  - Development of a plant uptake model for cyanide.
AB  - A model for cyanide species uptake by willow (Salix eriocephala L. var. Michaux)
      was developed to interpret data from hydroponic experiments quantitatively. While
      the potential for cyanide phytoremediation has been demonstrated modeling will
      aid in determining plant processes that contribute to cyanide transport and
      metabolism in willow and will target specific physiological parameters for field
      scale phytoremediation design and optimization. The objective of the model
      development was to gain insight into the relative role of different processes
      with respect to dissolved free and iron-complexed cyanide transport and
      assimilation in plants and to determine rates at which these processes occur
      within the willow plant under the experimental conditions. A physiologically
      based model describing plant uptake, transport, and metabolism of cyanide species
      was developed to reflect the processes that influence the movement of cyanide
      into and throughout the plant. Plant compartmentalization (root, stem, and leaf)
      corresponded to the level of detail in the data collected via hydroponic
      experiments. Inclusion of more detailed intra- and intercellular processes would
      create a model inconsistent with the macroscale nature of the data. Mass balances
      around each compartment were developed via kinetic representations for the mass
      transfer processes and were combined to form a model describing the fate of
      cyanide species within plant-water systems.

PMID- 16615307
TI  - Parameter estimation of a plant uptake model for cyanide: application to
      hydroponic data.
AB  - A plant uptake model is applied to describe free cyanide and ferrocyanide
      transport and fate in willow (Salix eriocephala var. Michaux) grown in
      hydroponics. The model is applied to experimental data to determine best-fit
      parameter values, their associated uncertainty, and their relative importance to
      field-scale phytoremediation applications. The fitted model results, using least
      squares optimization of the observed log concentrations, indicate that free
      cyanide volatilization from leaf tissue and free cyanide cell wall adsorption
      were negligible. The free cyanide maximum uptake rate and assimilate (noncyanide
      15N) first-order leaf loss rate were the only coefficients that significantly
      affected the model goodness of fit and were concurrently sensitive to data
      uncertainty in the parameter optimization. Saturation kinetics may be applicable
      for free cyanide uptake into plants, but not for ferrocyanide uptake, which may
      occur via preferential protein-mediated or inefficient transpiration stream
      uptake. Within the free cyanide system, the relative magnitudes of the saturation
      uptake parameters and the demonstration of an active role for plants in uptake
      relative to transpiration suggest the potential importance of preferential
      diffusion through the cell membranes as reported in the literature, rather than
      protein-mediated uptake. The fitted 13-parameter model matched the observed data
      well except for the predicted stem and leaf tissue assimilate concentrations,
      which were significantly underestimated, particularly in the free cyanide system.
      These low predicted values, combined with the slightly underestimated solution
      free cyanide removal, suggest that noncyanide 15N redistribution in phloem should
      be considered.

PMID- 16615308
TI  - Influence of citric acid amendments on the availability of weathered PCBs to
      plant and earthworm species.
AB  - A series of small and large pot trials were conducted to assess the
      phytoextraction potential of several plant species for weathered polychlorinated
      biphenyls (PCBs) in soil (105 microg/g Arochlor 1268). In addition, the effect of
      citric acid on PCB bioavailability to both plants and earthworms was assessed.
      Under small pot conditions (one plant, 400 g soil), three cucurbits (Cucurbita
      pepo ssp pepo [zucchini] and ssp ovifera [nonzucchini summer squash], Cucumis
      sativus, cucumber) accumulated up to 270 microg PCB/g in the roots and 14
      microg/g in the stems, resulting in 0.10% contaminant removal from soil. Periodic
      1 mM subsurface amendments of citric acid increased the stem and leaf PCB
      concentration by 330 and 600%, respectively, and resulted in up to a 65% increase
      in the total amount of contaminant removed from soil. Although citric acid at 10
      mM more than doubled the amount of PCB desorbed in abiotic batch slurries,
      contaminant accumulation by two earthworm species (Eisenia foetida and Lumbricus
      terrestris) was unaffected by citric acid at 1 and 10 mM and ranged from 11-15
      microg/g. Two large pot trials were conducted in which cucurbits (C. pepo ssp
      pepo and ssp ovifera, C. sativus) and white lupin (Lupinus albus) were grown in
      70 kg of PCB-contaminated soil White lupin was the poorest accumulator of PCBs,
      with approximately 20 microg/g in the roots and 1 microg/g in the stems. Both C.
      pepo ssp ovifera (summer squash) and C. sativus (cucumber) accumulated
      approximately 65-100 microg/g in the roots and 6-10 microg/g in the stems. C.
      pepo ssp pepo (zucchini) accumulated significantly greater levels of PCB than all
      other species, with 430 microg/g in the roots and 22 microg/g in the stems. The
      mechanism by which C. pepo spp pepo extracts and translocates weathered PCBs is
      unknown, but confirms earlier findings on the phytoextraction of other weathered
      persistent organic pollutants such as chlordane, p,p'-DDE, and polycyclic
      aromatic hydrocarbons.

PMID- 16615309
TI  - Leaching of contaminated leaves following uptake and phytoremediation of RDX,
      HMX, and TNT by poplar.
AB  - The uptake and fate of 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro
      1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX)
      by hybrid poplars in hydroponic systems were compared and exposed leaves were
      leached with water to simulate potential exposure pathways from groundwater in
      the field. TNT was removed from solution more quickly than nitramine explosives.
      Most of radioactivity remained in root tissues for 14C-TNT, but in leaves for 14C
      RDX and 14C-HMX. Radiolabel recovery for TNT and HMX was over 94%, but that of
      RDX decreased over time, suggesting a loss of volatile products. A considerable
      fraction (45.5%) of radioactivity taken up by whole plants exposed to 14C-HMX was
      released into deionized water, mostly as parent compound after 5 d of leaching.
      About a quarter (24.0%) and 1.2% were leached for RDX and TNT, respectively,
      mostly as transformed products. Leached radioactivity from roots was
      insignificant in all cases (< 2%). This is the first report in which small
      amounts of transformation products of RDX leach from dried leaves following
      uptake by poplars. Such behavior for HMX was reported earlier and is reconfirmed
      here. All three compounds differ substantially in their fate and transport during
      the leaching process.

PMID- 16615310
TI  - [Should accessory pudendal arteries be spared in radical prostatectomy?].

PMID- 16615311
TI  - [My first T.O.T].

PMID- 16615312
TI  - [Histological changes in normal and cancerous prostate after treatment (hormone
      therapy and radiotherapy) and their impact on the interpretation of the Gleason
      Score].

PMID- 16615313
TI  - [Urologic cancer in patients with kidney transplantation].

PMID- 16615314
TI  - [Stage I testicular seminoma: adjuvant treatment or surveillance?].

PMID- 16615315
TI  - [Should parapelvic renal cysts be treated?].

PMID- 16615316
TI  - An oscillator model of the timing of turn-taking.
AB  - When humans talk without conventionalized arrangements, they engage in
      conversation--that is, a continuous and largely nonsimultaneous exchange in which
      speakers take turns. Turn-taking is ubiquitous in conversation and is the normal
      case against which alternatives, such as interruptions, are treated as violations
      that warrant repair. Furthermore, turn-taking involves highly coordinated timing,
      including a cyclic rise and fall in the probability of initiating speech during
      brief silences, and involves the notable rarity, especially in two-party
      conversations, of two speakers' breaking a silence at once. These phenomena,
      reported by conversation analysts, have been neglected by cognitive
      psychologists, and to date there has been no adequate cognitive explanation.
      Here, we propose that, during conversation, endogenous oscillators in the brains
      of the speaker and the listeners become mutually entrained, on the basis of the
      speaker's rate of syllable production. This entrained cyclic pattern governs the
      potential for initiating speech at any given instant for the speaker and also for
      the listeners (as potential next speakers). Furthermore, the readiness functions
      of the listeners are counterphased with that of the speaker, minimizing the
      likelihood of simultaneous starts by a listener and the previous speaker. This
      mutual entrainment continues for a brief period when the speech stream ceases,
      accounting for the cyclic property of silences. This model not only captures the
      timing phenomena observed inthe literature on conversation analysis, but also
      converges with findings from the literatures on phoneme timing, syllable
      organization, and interpersonal coordination.

PMID- 16615319
TI  - From brief gaps to very long pauses: temporal isolation does not benefit serial
      recall.
AB  - Theoretical explanations of short-term memory for serial order can be classified
      on the basis of whether or not they invoke time as a causal variable. According
      to time-based accounts, such as temporal distinctiveness theories, there is an
      intimate link between time and memory. Event-based theories, by contrast,
      postulate processes such as interference or rehearsal to account for seemingly
      temporal phenomena in short-term memory. We report an experiment that examined
      whether extended temporal isolation benefits serial recall performance.
      Regardless of whether the participants were quiet or performed articulatory
      suppression during list presentation, temporal isolation did not benefit memory
      even if items were separated from their neighbors by up to 7 sec. These findings
      challenge time-based theories of short-term memory.

PMID- 16615317
TI  - Sensorimotor synchronization: a review of the tapping literature.
AB  - Sensorimotor synchronization (SMS), the rhythmic coordination of perception and
      action, occurs in many contexts, but most conspicuously in music performance and
      dance. In the laboratory, it is most often studied in the form of finger tapping
      to a sequence of auditory stimuli. This review summarizes theories and empirical
      findings obtained with the tapping task. Its eight sections deal with the role of
      intention, rate limits, the negative mean asynchrony, variability, models of
      error correction, perturbation studies, neural correlates of SMS, and SMS in
      musical contexts. The central theoretical issue is considered to be how best to
      characterize the perceptual information and the internal processes that enable
      people to achieve and maintain SMS. Recent research suggests that SMS is
      controlled jointly by two error correction processes (phase correction and period
      correction) that differ in their degrees of cognitive control and may be
      associated with different brain circuits. They exemplify the general distinction
      between subconscious mechanisms of action regulation and conscious processes
      involved in perceptual judgment and action planning.

PMID- 16615318
TI  - Hemispheric asymmetries in the time course of recognition memory.
AB  - Hemispheric specialization has been studied extensively within subfields ranging
      from perception to language comprehension. However, the study of asymmetries for
      basic memory functions--an area that holds promise for bridging these low- and
      high-level cognitive domains--has been sporadic at best. We examined each
      hemisphere's tendency to retain verbal information over time, using a continuous
      recognition memory task with lateralized study items and central test probes. We
      found that the ubiquitous advantage of the left hemisphere for the processing and
      retention of verbal information is attenuated and perhaps even reversed over long
      retention intervals. This result is consistent with theories that propose
      differences in the degree to which the hemispheres maintain veridical versus
      semantically transformed representations of the input they receive.

PMID- 16615320
TI  - Transfer of directed-forgetting cues across discrimination tasks with pigeons.
AB  - Directed forgetting is shown as impaired performance on a memory test following
      an instruction that the presented items will not be tested. Experiments utilizing
      the delayed matching-to-sample (DMTS) task have demonstrated that this ability to
      actively control memory is present in animals; however, no study has yet
      confirmed that cues to forget established in one DMTS discrimination will
      successfully transfer to other discriminations. Lacking such evidence, it is not
      clear whether forgetting cues act as "higher level" task instructions or are
      represented more simply, perhaps as part of a sample-specific sequence of events.
      The present study revealed good transfer of the forget cue function in pigeons
      after prior training with the forget cues in a separate discrimination. This
      finding is discussed in relation to analogous experiments on occasion setting, in
      which training within more than one discriminative context has been shown to be
      critical to the transfer of a conditional relation.

PMID- 16615321
TI  - Distraction and action slips in an everyday task: evidence for a dynamic
      representation of task context.
AB  - We report here a novel and counterintuitive effect of distraction on routine
      sequential action. The effect, predicted by a recent computational model of
      sequential behavior, relates to the tendency for a momentary distraction, such as
      a brief interruption, to lead to subsequent slips of action. The specific
      prediction is that errors should be more likely following a distraction occurring
      toward the middle of a subtask sequence than following a distraction occurring at
      the end of a subtask. This was tested and confirmed in an experiment involving
      repeated performance of an everyday task (coffee making) under conditions
      involving frequent interruption. The observed effect provides differential
      support for existing models of sequential behavior and offers a highly
      constraining benchmark for future theories.

PMID- 16615322
TI  - Syntactic class influences phonological priming of tip-of-the-tongue resolution.
AB  - During tip-of-the-tongue (TOT) experiences, phonologically related words have
      both facilitated and impeded word retrieval. In the present experiment, we
      examined whether phonologically related words' syntactic class (part of speech)
      is responsible for these differential effects. Sixty college students saw general
      knowledge questions whose answers were designated target words and responded
      "know," "don't know," or "TOT." Following "TOT" and "don't know" responses, the
      participants saw five words, one of which was a prime. The primes contained the
      target's first syllable and either shared or did not share the target's part of
      speech. Following presentation of the primes, retrieval of the target was
      attempted again. Different-part-of-speech primes facilitated resolution of TOT
      states, whereas same-part-of-speech primes had no effect, relative to
      phonologically unrelated words. These results support node structure theory's
      most-primed-wins principle and the transmission deficit model account of TOT
      states and detail the importance of syntactic class in the selection of words
      that are candidates for speech production.

PMID- 16615323
TI  - Spatial orienting of tactile attention induced by social cues.
AB  - Several studies have established that humans orient their visual attention
      reflexively in response to social cues such as the direction of someone else's
      gaze. However, the consequences of this kind of orienting have been addressed
      only for the visual system. We investigated whether visual social attention cues
      can induce shifts in tactile attention by combining a central noninformative eye
      gaze cue with tactile targets presented to participants' fingertips. Data from
      speeded detection, speeded discrimination, and signal detection tasks converged
      on the same conclusion: Eye-gaze-based orienting facilitates the processing of
      tactile targets at the location of the gazed-at body location. In addition, we
      examined the effects of other directional cues, such as conventional arrows, and
      found that they can be equally effective. This is the first demonstration that
      social attention cues have consequences that reach beyond their own sensory
      modality.

PMID- 16615324
TI  - Distinctiveness, typicality, and recollective experience in face recognition: a
      principal components analysis.
AB  - In this study, participants rated previously unseen faces on six dimensions:
      familiarity, distinctiveness, attractiveness, memorability, typicality, and
      resemblance to a familiar person. The faces were then presented again in a
      recognition test in which participants assigned their positive recognition
      decisions to either remember (R), know (K), or guess categories. On all
      dimensions except typicality, faces that were categorized as R responses were
      associated with significantly higher ratings than were faces categorized as K
      responses. Study ratings for R and K responses were then subjected to a principal
      components analysis. The factor loadings suggested that R responses were
      influenced primarily by the distinctiveness of faces, but K responses were
      influenced by moderate ratings on all six dimensions. These findings indicate
      that the structural features of a face influence the subjective experience of
      recognition.

PMID- 16615325
TI  - Effects of processing bias on the recognition of composite face halves.
AB  - Research has shown that face recognition accuracy can be improved by prior global
      processing and impaired by prior local processing (Macrae & Lewis, 2002). The aim
      of this study was to test the processing bias account of face recognition, using
      the composite face task (Young, Hellawell, & Hay, 1987), a test of featural
      recognition. Undergraduate volunteers (N = 75) participated in a between-subjects
      design that tested their ability to recognize face halves within a composite,
      following either global or local Navon processing or a control task. Results
      showed that, as compared with the control task, local processing speeded ability
      to recognize face halves. These results provide support for the processing bias
      account of face recognition.

PMID- 16615326
TI  - An own-age bias in face recognition for children and older adults.
AB  - In the present study, we examined whether children and older adults exhibit an
      own-age face recognition bias. Participants studied photographs of children,
      younger adults, middle-aged adults, and older adults and were administered a
      recognition test. Results showed that both children and older adults more
      accurately recognized own-age faces than other-age faces. These data suggest that
      individuals may acquire expertise for identifying faces from their own age group
      and are discussed in terms of Sporer's (2001) in-group/out-group model of face
      recognition.

PMID- 16615327
TI  - Faces retain attention.
AB  - In the present study, we investigated whether faces have an advantage in
      retaining attention over other stimulus categories. In three experiments,
      subjects were asked to focus on a central go/no-go signal before classifying a
      concurrently presented peripheral line target. In Experiment 1, the go/no-go
      signal could be superimposed on photographs of upright famous faces, matching
      inverted faces, or meaningful objects. Experiments 2 and 3 tested upright and
      inverted unfamiliar faces, printed names, and another class of meaningful objects
      in an identical design. A fourth experiment provided a replication of Experiment
      1, but with a 1,000-msec stimulus onset asynchrony between the onset of the
      central face/nonface stimuli and the peripheral targets. In all the experiments,
      the presence of an upright face significantly delayed target response times, in
      comparison with each of the other stimulus categories. These results suggest a
      general attentional bias, so that it is particularly difficult to disengage
      processing resources from faces.

PMID- 16615328
TI  - Cross-cultural similarities and differences in North Americans' geographic
      location judgments.
AB  - We examined some potential causes of bias in geographic location estimates by
      comparing location estimates of North American cities made by Canadian, U.S., and
      Mexican university students. All three groups placed most Mexican cities near the
      equator, which implies that all three groups were influenced by shared beliefs
      about the locations of geographical regions relative to global reference points.
      However, the groups divided North America into different regions and differed in
      the relative accuracy of the estimates within them, which implies that there was
      an influence of culture-specific knowledge. The data support a category-based
      system of plausible reasoning, in which biases in judgments are multiply
      determined, and underscore the utility of the estimation paradigm as a tool in
      cross-cultural cognitive research.

PMID- 16615329
TI  - Object appearance, disappearance, and attention prioritization in real-world
      scenes.
AB  - We examined the prioritization of abruptly appearing and disappearing objects in
      real-world scenes. These scene changes occurred either during a fixation
      (transient appearance/disappearance) or during a saccade (nontransient
      appearance/disappearance). Prioritization was measured by the eyes' propensity to
      be directed to the region of the scene change. Object additions and deletions
      were fixated at rates greater than chance, suggesting that both types of scene
      change arecues used by the visual system to guide attention during scene
      exploration, although appearances were fixated twice as often as disappearances,
      indicating that new objects are more salient than deleted objects. New and
      deleted objects were prioritized sooner and more frequently if they occurred
      during a fixation, as compared with during a saccade, indicating an important
      role of the transient signal that often accompanies sudden changes in scenes. New
      objects were prioritized regardless of whether they appeared during a fixation or
      a saccade, whereas prioritization of a deleted object occurred only if (1) a
      transient signal was present or (2) the removal of the object revealed previously
      occluded objects.

PMID- 16615330
TI  - The subjective size of melodic intervals over a two-octave range.
AB  - Musically trained and untrained participants provided magnitude estimates of the
      size of melodic intervals. Each interval was formed by a sequence of two pitches
      that differed by between 50 cents (one half of a semitone) and 2,400 cents (two
      octaves) and was presented in a high or a low pitch register and in an ascending
      or a descending direction. Estimates were larger for intervals in the high pitch
      register than for those in the low pitch register and for descending intervals
      than for ascending intervals. Ascending intervals were perceived as larger than
      descending intervals when presented in a high pitch register, but descending
      intervals were perceived as larger than ascending intervals when presented in a
      low pitch register. For intervals up to an octave in size, differentiation of
      intervals was greater for trained listeners than for untrained listeners. We
      discuss the implications for psychophysical pitch scales and models of music
      perception.

PMID- 16615331
TI  - A role for set when naming Arabic numerals: how intentionality limits (putatively
      automatic) performance.
AB  - Processing in various skilled domains is often described as automatic, in the
      sense that functional stimulus processing is triggered by stimulus onset and
      cannot be interrupted. One problem is that subjects typically know what task they
      have to perform prior to stimulus presentation. Various effects attributed to
      automatic processing may, therefore, arise instead from the mental set that is
      already in place. In the present study, we investigated skilled subjects' ability
      to engage in processing prior to knowing what the task is. A numeral was
      presented, and subjects either named it or added 1 and named the result. Which
      task was to be performed on a trial was signaled by a tone that appeared before
      or at the same time as the target. If functional target processing is triggered
      by its presentation, the effect of low contrast should be absorbed into the time
      taken to decode the task cue, regardless of the task (the effect of contrast
      should be absent at the 0-msec stimulus onset asynchrony [SOA] and present when
      task information is given in advance of the target). An underadditive interaction
      between contrast and SOA was seen for one task, but these factors had additive
      effects in the other task. This pattern can be understood in terms of the
      hypothesis that although encoding can be thought of as a stage common to both
      tasks, it is not, in the present context, functionally independent of a
      subsequent stage unique to a task.

PMID- 16615332
TI  - Concept mediation in trilingual translation: evidence from response time and
      repetition priming patterns.
AB  - Translation responses to individual words were elicited from 48 English-Spanish
      French trilinguals, who translated in six directions at study and two directions
      at test. Patterns of translation response times and error rates at study
      reflected the relative proficiency of the trilinguals in comprehension and
      production of their three languages. At test, repeated items were translated more
      quickly than new items, with the strongest priming effects occurring for
      identical repetitions. Repetition priming was also substantial when only the
      stimulus language or only the response language matched from study to test,
      implying that repeated comprehension and production processes contribute to
      priming in translation. Patterns of response times and repetition priming
      indicate that translation in all directions involved conceptual access. Additive
      patterns in response time asymmetries and repetition priming were consistent with
      the treatment of word comprehension and production processes of translation as
      independent.

PMID- 16615333
TI  - The effect of word predictability on the eye movements of Chinese readers.
AB  - Eye movements of Chinese readers were monitored as they read sentences containing
      target words whose predictability from the preceding context was high, medium, or
      low. Readers fixated for less time on high- and medium-predictable target words
      than on low-predictable target words. They were also more likely to fixate on low
      predictable target words than on high- or medium-predictable target words. The
      results were highly similar to those of a study by Rayner and Well (1996) with
      English readers and demonstrate that Chinese readers, like readers of English,
      exploit target word predictability during reading.

PMID- 16615334
TI  - Evidence for a modality effect in sentence retention.
AB  - It is well known that an acoustic-sensory code supports retention of linguistic
      materials whose storage is particularly based on phonological information (e.g.,
      unrelated word lists). The present study investigates whether such a code also
      contributes to the retention of sentences. It has been shown that short-term
      sentence recall particularly depends on propositional and lexicosemantic
      information, which are assumed to be supplied independently of modality
      influences. We employed the intrusion paradigm of Potter and Lombardi (1990) and
      manipulated the availability of acoustic-sensory information. Participants were
      instructed to read sentences either silently or aloud. Since these two reading
      conditions also differ with respect to articulatory information, a further
      condition that provided articulatory but not acoustic-sensory information was
      introduced (i.e., silent mouthing). Our data suggest that acoustic-sensory
      information is used, if available, even in sentence recall.

PMID- 16615335
TI  - Age-related differences in automatic stimulus-response associations: insights
      from young and older adults' parity judgments.
AB  - Young and older adults completed a parity judgment task (i.e., judging whether a
      target digit was odd or even) in which target numbers were preceded by masked
      prime numbers presented for 43 msec. Targets were either congruent (i.e., they
      had the same parity status as their primes) or incongruent (i.e., odd primes were
      paired with even targets, and even primes were paired with odd targets). Response
      times, percent errors, and event-related potentials (ERPs) were recorded for all
      items to compare automatic stimulus-response association (ASRA) and congruence
      effects (i.e., better performance on congruent than on incongruent trials) across
      age groups. Two important original sets of findings were obtained in this sample
      of participants. First, both age groups showed ASRA effects in behavioral
      measures. Second, age-related differences were observed in amplitude, timing, and
      scalp distributions for each congruent and incongruent ERP. These findings have
      implications for furthering the understanding of ASRA effects and of general
      characteristics of cognitive processes affected (or not affected) by aging.

PMID- 16615336
TI  - Attentional bias affects change detection.
AB  - Thirty smokers and 30 nonsmokers participated in a flicker study in which the
      role of attentional bias in change detection was examined. The participants
      observed picture pairs of everyday objects flicker on a computer screen until
      they detected the one object that had changed. In half of the pictures, a smoking
      related object (e.g., a lighter) was included among smoking-unrelated objects
      (e.g., a spoon). Half of the smokers and half of the nonsmokers were aware of the
      experiment's focus, and the other half were not. The smokers exhibited shorter
      detection latencies than did the nonsmokers when a smoking object changed and
      longer detection latencies when a nonsmoking object changed while a smoking
      object was present, and they exhibited detection latencies similar to those of
      the nonsmokers when smoking objects were not present. Interestingly, the
      nonsmokers displayed the same attentional bias as the smokers when they were
      aware of the experiment's smoking focus, but they did not display any attentional
      bias when they were unaware. Thus, these findings provide evidence for long-term
      context-independent, as well as for short-term context-dependent, attentional
      bias.

PMID- 16615337
TI  - Temporal expectations modulate attentional capture.
AB  - Subjects' ability to override attentional capture by salient distractors during
      singleton search has been attributed to the adoption of an attentional set for
      the type of discontinuity characterizing the target (Folk, Remington, & Johnston,
      1992) or to fast disengagement of attention from the salient distractor's
      location (Theeuwes, Atchley, & Kramer, 2000). The present results support an
      alternative account by showing that temporal expectancies modulate attentional
      capture. In a color singleton search, an irrelevant onset preceding the target by
      a given time interval produced capture when the distractor-to-target interval
      varied unpredictably but failed to do so when this interval was predictable.
      Moreover, with unpredictable intervals and moderately salient stimuli, capture
      was overridden at the expected average interval. These findings invite caution
      when stimulus onset asynchrony manipulations are used to study the temporal
      deployment of attention, since they demonstrate that such manipulations introduce
      powerful temporal expectations.

PMID- 16615338
TI  - Marking rejected distractors: a gaze-contingent technique for measuring memory
      during search.
AB  - There is a debate among search theorists as to whether search exploits a memory
      for rejected distractors. We addressed this question by monitoring eye movements
      and explicitly marking objects visited by gaze during search. If search is
      memoryless, markers might be used to reduce distractor reinspections and improve
      search efficiency, relative to a no-marking baseline. However, if search already
      uses distractor memory, there should be no differences between marking and no
      marking conditions. In four experiments, with stimuli ranging from Os and Qs to
      realistic scenes, two consistent data patterns emerged: (1) Marking rejected
      distractors produced no systematic benefit for search efficiency, as measured by
      reinspections, reaction times, or errors, and (2) distractor reinspection rates
      were, overall, extremely low. These results suggest that search uses a memory for
      rejected distractors, at least in those many real-world search tasks in which
      gaze is free to move.

PMID- 16615339
TI  - Visual working memory for simple and complex visual stimuli.
AB  - Does the magical number four characterize our visual working memory (VWM)
      capacity for all kinds of objects, or is the capacity of VWM inversely related to
      the perceptual complexity of those objects? To find out how perceptual complexity
      affects VWM, we used a change detection task to measure VWM capacity for six
      types of stimuli of different complexity: colors, letters, polygons, squiggles,
      cubes, and faces. We found that the estimated capacity decreased for more complex
      stimuli, suggesting that perceptual complexity was an important factor in
      determining VWM capacity. However, the considerable correlation between
      perceptual complexity and VWM capacity declined significantly if subjects were
      allowed to view the sample memory display longer. We conclude that when encoding
      limitations are minimized, perceptual complexity affects, but does not determine,
      VWM capacity.

PMID- 16615340
TI  - Effects of a Campylobacter jejuni infection on the development of the intestinal
      microflora of broiler chickens.
AB  - The effect of a Campylobacter jejuni colonization on the development of the
      microflora of the cecum and the ileum of broiler chickens was studied using
      molecular methods. The infection did affect the development and complexity of the
      microbial communities of the ceca, but we found no permanent effect of a C.
      jejuni infection on the ileal microflora of the broilers. In addition, denaturant
      gradient gel electrophoresis (DGGE) profiles generated from cecal and ileal
      contents revealed several DGGE bands that were present in the control chickens,
      but not in the chickens colonized with C. jejuni. Some of these DGGE bands could
      be affiliated with Lactobacillus reuteri, Clostridium perfringens, and the genus
      Klebsiella.

PMID- 16615341
TI  - Effect of glycerol monocaprate (monocaprin) on broiler chickens: an attempt at
      reducing intestinal Campylobacter infection.
AB  - Attempts have been made by several workers to prevent or to reduce colonization
      of Campylobacter in the intestines of broiler chickens by adding antibacterial
      agents to their food, but the results have varied. Monocaprin, the 1
      monoglyceride of capric acid, has been found to be very active in killing
      Campylobacter in vitro. It was therefore studied whether Campylobacter infection
      in chickens would be affected by adding emulsions of monocaprin to their drinking
      water and feed. It was found that treatment with monocaprin in water and feed did
      not prevent spread of Campylobacter from artificially infected to noninfected 24
      d-old chickens, but Campylobacter counts in cloacal swabs were significantly
      reduced, particularly during the first 2 d of treatment. There was also a
      significant reduction in the Campylobacter counts in cloacal swabs of naturally
      infected 36-d-old broilers that were treated for 3 d prior to slaughter. Addition
      of monocaprin to drinking water and feed 2 to 3 d before slaughter might
      therefore be considered as a means of reducing Campylobacter infection in
      broilers, possibly in conjunction with other antibacterial agents such as short
      chain organic acids. Further studies are needed to determine whether this would
      reduce carcass contamination.

PMID- 16615342
TI  - Identification of trait loci affecting white meat percentage and other growth and
      carcass traits in commercial broiler chickens.
AB  - White meat is the most economically valuable part of a broiler chicken.
      Increasing white meat relative to overall body size (white meat percentage, WM%)
      makes a broiler, gram for gram, a more valuable animal. However, accurately
      measuring WM% requires removing the bird from the breeding flock. Identification
      of markers for genomic regions associated with WM% would allow direct genetic
      selection on breeders. The objective of the current study was to identify genomic
      regions affecting WM% and other growth and carcass traits in an F2 cross between
      2 commercial broiler lines that differed in WM%. Two commercial lines were
      crossed to generate 5 F1 half-sib families of each reciprocal cross type. One
      male from each family was crossed with 3 females from each of the other families
      within each reciprocal cross type. Seven F2 half-sib families, totaling 430 F2
      individuals, were analyzed. Microsatellite markers (n = 73) on the 11 largest
      chromosomes were analyzed for associations with various growth and carcass traits
      by least squares interval mapping using line-cross, half-sib, combined, and
      parent of origin models. Sixty-eight QTL were identified at the 5% chromosome
      wise level, including 6 QTL affecting WM%. Ten QTL reached 5% genome-wise
      significance, including 1 WM% QTL on Gga 2. The current study identified genomic
      regions harboring QTL affecting WM% and other carcass and growth traits, which
      may be useful for direct genetic selection, and also identified putative
      imprinted QTL in the chicken. The advantage of using multiple statistical models
      was evident because QTL were identified with the combined and parent of origin
      models that were not identified with the line-cross or half-sib models.

PMID- 16615343
TI  - Single nucleotide polymorphism discovery in the avian Tapasin gene.
AB  - Tapasin is a transmembrane glycoprotein located in the endoplasmic reticulum. Its
      function is to assist the assembly of major histocompatibility complex class I
      molecules. The chicken Tapasin gene includes 8 exons and is localized inside the
      major histocompatibility complex between the 2 class IIbeta genes. The aim of the
      current study was the estimation of single nucleotide polymorphism frequency
      within the avian Tapasin gene. The Tapasin gene sequence from exon 5 to exon 6
      was amplified for the chicken, turkey, and pheasant, and sequences of different
      lengths were obtained. The sequence analysis based on PolyBayes identified 25
      putative single nucleotide polymorphism sites when the 3 species were compared.
      The coding sequences were further translated and analyzed to identify amino acid
      substitutions. The results indicated that polymorphisms within this region of the
      gene was mainly observed in the heterozygous state. The level of conservation of
      the Tapasin gene sequence among species is likely to be related to the functional
      importance of the gene.

PMID- 16615344
TI  - Limited treatment with beta-1,3/1,6-glucan improves production values of broiler
      chickens challenged with Escherichia coli.
AB  - The development of antibiotic-resistant bacteria has led to a need for
      alternatives to antibiotics for growth promotion and disease prevention in
      poultry production. The helical polysaccharide beta-1,3/1,6-glucan is derived
      from the cell wall of Saccharomyces cervisiae and has immunomodulating
      activities. The objective of this study was to determine the ability of 2
      supplementation programs with a commercial beta-1,3/1,6-glucan product to protect
      broiler chicks from experimental respiratory challenge with Escherichia coli.
      Chicks were housed in battery-brooders from 1 d of age and fed a standard starter
      diet or the same diet containing 20 g/ton (22 ppm) of purified beta-1,3/1,6
      glucan either continuously (BG25d) or for only the first 7 d prior to challenge
      (BG7d). At d 7 one-half of the birds were inoculated in the thoracic air sac with
      800 cfu of a serotype O2, nonmotile strain of E. coli. All surviving birds were
      necropsied at d 25. Body weight of survivors and feed conversion efficiency were
      protected from the adverse effects of E. coli challenge by BG7d but not by BG25d.
      Mortality was nominally decreased from 63% (control) to 53% in BG25d and 47% in
      BG7d, but these decreases were not significant. The relative weights of the liver
      and heart were increased, and the bursa of Fabricius relative weights were
      decreased by E. coli challenge, and these effects were modulated by beta-glucan
      treatment. Despite positive effects of BG7d in E. coli-challenged birds, the BW
      of nonchallenged birds was decreased by BG7d and BG25d. These results suggest
      that supplementation of broiler diets with beta-1,3/1,6-glucan may be valuable
      for decreasing production losses due to E. coli respiratory disease, but that the
      immune stimulation provided may also result in decreased production values under
      experimental battery conditions or for birds raised in an environment with
      minimal disease challenges.

PMID- 16615345
TI  - Apparent attachment of Campylobacter and Salmonella to broiler breeder rooster
      spermatozoa.
AB  - It has been demonstrated that horizontal and vertical transmission of Salmonella
      and Campylobacter can occur in broiler breeder flocks. The mechanism of this
      transmission is still unclear. Previously negative broiler breeder flocks have
      been reported to become positive with Salmonella, Campylobacter, or both after
      the introduction of "spike" roosters at 45 wk of age. To determine whether the
      rooster semen is a possible source of transmission to hens for colonization, we
      evaluated the association of both Salmonella and Campylobacter spp. to segments
      (head, midpiece, and tail) of individual spermatozoa after artificial
      inoculation. Salmonella typhimurium, Salmonella heidelberg, and Salmonella
      montevideo, or Campylobacter jejuni (in 0.85% saline) was added to a freshly
      collected (by abdominal massage) aliquot of pooled semen from roosters housed in
      individual cages. The semen and bacteria solutions were incubated 1 h at room
      temperature. Samples were fixed using Karnosvsky and Zamboni fixatives for 24 h
      prior to centrifuging and rinsing in 0.1 M cacodylate x HCl buffer. Individual
      aliquot samples were then subjected to both scanning (JSM-5800) and transmission
      (JEM-1210) electron microscopy. The scanning electron microscopy showed that
      Salmonella was associated with all 3 segments (head, midpiece, and tail) of the
      spermatozoa and apparently equally distributed. Campylobacter was mainly
      associated with the midpiece and tail segments; few isolates were located on the
      head segment. The transmission electron microscopy showed apparent attachment of
      Salmonella and Campylobacter to the spermatozoa.

PMID- 16615346
TI  - Comparison of apparent ileal amino acid digestibility of feed ingredients
      measured with broilers, layers, and roosters.
AB  - The apparent ileal digestibility of amino acids in 7 feed ingredients was
      determined using broilers, layers, and roosters. The ingredients included 3
      cereals (wheat, sorghum, and corn), 3 oilseed meals (canola, cottonseed, and
      soybean meals), and 1 animal protein meal (meat and bone meal). Dietary protein
      in the assay diets was supplied solely by the test ingredient. All diets
      contained 20 g/kg of acid-insoluble ash as an indigestible marker, and each diet
      was offered ad libitum in mash form to 5 replicate pens of broilers and layers,
      and 4 replicate pens of roosters. The digestibility coefficients of individual
      amino acids for wheat, corn, and sorghum were higher (P < 0.05) in broilers than
      in layers and roosters. The digestibility of most amino acids for corn and
      sorghum was higher (P < 0.05) in roosters compared with those in layers, whereas
      the digestibility for wheat in layers and roosters was similar. In general, the
      digestibility of amino acids in canola meal, cottonseed meal, and meat and bone
      meal was similar among the 3 classes of chickens. The digestibility of amino
      acids in soybean meal was higher (P < 0.05) for layers compared with those for
      broilers and roosters but similar between broilers and roosters. These results
      suggest that the class of chickens significantly influenced the apparent ileal
      digestibility of amino acids in some feed ingredients.

PMID- 16615347
TI  - Nutritional evaluation of raw and extruded kidney bean (Phaseolus vulgaris L.
      var. pinto) in chicken diets.
AB  - An experiment was conducted to study the effect of inclusion of different
      concentrations (0, 100, 200, and 300 g/kg) of raw kidney bean and extruded kidney
      bean in broiler chick (0 to 21 d of age) diets on performance, digestive organ
      sizes, protein and amino acid digestibilities, intestinal viscosity, cecal pH,
      and blood parameters. Data were analyzed as a 3 x 2 factorial arrangement with 3
      levels of kidney bean with and without extrusion. Positive control without kidney
      bean was used. Increasing the kidney bean content in the diet reduced weight gain
      and consumption, and increased the feed-to-gain ratio. Relative pancreas, liver,
      and jejunum weights, and intestinal viscosity were increased in response to
      increasing kidney bean concentration in the diet. The inclusion of different
      concentrations of kidney bean did not affect the apparent ileal digestibility of
      essential and nonessential amino acids, except for Met, Phe, and Cys, which were
      increased. Increasing kidney bean in the diet did not affect blood parameters,
      except for total protein, which was increased, and for androstenedione and
      testosterone, which were reduced. Extrusion significantly improved weight gain,
      feed consumption, and feed conversion. Relative pancreas, liver, and jejunum
      weights were reduced and spleen weight, cecal and intestinal viscosity were
      increased by extrusion. Apparent ileal digestibility of crude protein and all
      essential and nonessential amino acids were improved by extrusion. Like-wise,
      extrusion increased significantly the concentrations of cholesterol,
      triglycerides, glucose, and testosterone. We concluded that the inclusion of
      kidney bean in chicken diets cause a negative effect on performance and CP and
      amino acid digestibilities, and modified digestive organ sizes, intestinal
      viscosity, cecal pH, and some blood parameters. These effects were counteracted
      by the extrusion of kidney bean. However, the inclusion of extruded kidney bean
      in a chick diet resulted in poorer performance compared with that obtained with a
      corn-soybean diet.

PMID- 16615348
TI  - Histological intestinal recovery in chickens refed dietary sugar cane extract.
AB  - Sugar cane extract (SCE), the residue after removing glucose, fructose, and
      sucrose from sugar cane juice, has growth-promoting, antistress, and
      immunostimulation effects. The objective of this study was to investigate the
      effects of refeeding dietary SCE on recovery of BW and intestinal histology after
      withdrawing feed from chickens. Forty-eight male Sanuki Cochin chickens were
      assigned randomly to 6 treatments and 8 replicates in a completely randomized
      design. The 6 treatments were intact control chickens fed ad libitum a basal
      commercial grower mash diet; 3 d of feed withdrawal; feed withdrawal followed by
      1 d of ad libitum access to the same commercial mash diet (AFC); and free access
      to the commercial mash diet with 0.05, 1, or 3% SCE for 1 d. All SCE groups
      gained more weight in 1 d of refeeding than the AFC group (P < 0.05). Compared
      with the AFC group, the SCE groups increased cell mitosis (P < 0.05). On the
      villus apical surface, flat epithelial cells of the feed withdrawal group
      developed more protuberated cells than those of the intact control group in all
      refeeding groups. Compared with the AFC group, the SCE groups showed more
      protuberated cells. In addition, in the 0.05% SCE group, cell clusters aggregated
      by many cells were observed on the villus apical surface. The present
      histological intestinal alterations in chickens refed a SCE-containing diet
      demonstrate that the villi and epithelial cells might be hypertrophied because of
      some component in the SCE, resulting in quicker BW recovery in SCE-fed birds
      compared with those in the AFC group.

PMID- 16615349
TI  - Response of male BUT big 6 turkeys to varying amino acid feeding programs.
AB  - Dietary protein is a major cost contributor in turkey nutrition. Therefore, a
      feeding trial with male BUT Big 6 turkeys to 154 d of age was conducted to
      examine how live performance and economics are affected when dietary amino acid
      levels are altered in different phases. Six dietary treatments were run with
      treatment 1 as the control in which balanced protein levels were according to
      recommendations during all 6 phases. Treatments 2 through 6 used combinations of
      balanced protein (based on lysine) that ranged from 90 to 120% of those used in
      treatment 1. The combinations for the 6 phases of feeding were 120, 120, 120,
      120, 90, and 90% for treatment 2; 120, 120, 120, 100, 90, and 90% for treatment
      3; 120, 120, 100, 100, 90, and 90% for treatment 4; 120, 120, 120, 120, 100, and
      100% for treatment 5; and 90, 90, 90, 100, 100, and 100 for treatment 6. Final BW
      was highest in treatment 4 and lowest in treatment 2 (P < 0.05), whereas final BW
      were intermediate and statistically not different in treatments 1, 3, 5, and 6.
      Breast meat yield was highest in treatment 5 and lowest in treatments 2 and 3 (P
      < 0.05). Mortality seemed to be reduced in treatment 6 compared with treatments
      2, 3, and 5 (P < 0.10). Performance data in combination with economic simulations
      suggested that the feeding regimens of treatments 4 or 6 might be alternative
      strategies to treatment 1 to improve overall profitability.

PMID- 16615350
TI  - Estimation of true phosphorus digestibility and endogenous phosphorus loss in
      growing chicks fed conventional and low-phytate soybean meals.
AB  - This study evaluated regression of total P output against dietary P intake to
      simultaneously estimate endogenous P loss and true P utilization in broiler
      chicks. Soybean meal (SBM) served as the model ingredient, and a comparison was
      made between conventional and low-phytate SBM varieties. These feedstuffs were
      chosen to minimize nutritive differences to dietary phytate content. Low-phytate
      SBM contained 57% less phytate than conventional SBM. Four isocaloric diets were
      formulated to contain graded levels of each soybean meal (8 diets total);
      therefore, the diets also contained graded levels of dietary P. Chromium
      sesquioxide was included in diets as an indigestible marker, and free access to
      experimental diets was provided to 288 male broiler chicks from 15 to 22 d
      posthatch. The experiment was arranged as a randomized complete block design with
      6 blocks of 8 cages (6 birds per cage) and similar initial BW across dietary
      treatments. As P intake ranged from 0.9 to 3.9 g/ kg of DM, apparent prececal P
      digestibilities increased (linear and quadratic, P < 0.01) for conventional SBM
      and low-phytate SBM. Increasing linear relationships (P < 0.01) were observed for
      total P output (mg/kg of DM intake) with graded P intake, regardless of SBM
      variety. True P retention was greater (P < 0.01) for low-phytate SBM (76.9%) than
      for conventional SBM (59.8%). Endogenous P estimates were not different between
      soybean meals (P > 0.10), and an overall estimate of 235 mg of P/ kg of DM intake
      was observed. This study concluded 1) the regression approach may be applicable
      in the estimation of endogenous P loss in broiler chicks and 2) the difference in
      P utilization between conventional and low-phytate soybean meals is influenced by
      dietary phytate content when broiler chicks are fed P-deficient diets.

PMID- 16615351
TI  - Mucin gene expression and mucin content in the chicken intestinal goblet cells
      are affected by in ovo feeding of carbohydrates.
AB  - The protective mucus layer covers the entire surface of the gastrointestinal
      tract. The mucus layer also acts as a medium for molecule transport between the
      luminal contents and the enterocytes; therefore it has a major role in nutrient
      absorption. The main mucus layer component, mucin glycoproteins, is produced by
      mucous-secreting goblet cells. In chicken small intestine, functional development
      of goblet cells and enterocytes occurs in the late embryonic and immediate
      posthatch period. Presence of the nutrient is crucial for mucosal development.
      Feed deprivation immediately after hatch caused delayed mucosa development and
      perturbed mucin dynamics. Recent studies showed the intraamnionic nutrient supply
      (in-ovo feeding; IOF) accelerated mucosa functional development. In this study,
      the effect of IOF on the mucin mRNA expression and mucin content in the goblet
      cells was studied. The feeding solution containing carbohydrates was administered
      to the amnionic fluid of the Cobb embryos at d 17.5 of incubation. Samples from
      the jejunum were taken at d 17 of incubation (before IOF), and then 10 embryos
      from each group were sampled at 19 d of incubation, at hatch, and at d 3
      posthatch. Following IOF, villus surface area increased at day of hatch and 3 d
      posthatch by 27 and 21%, respectively. In addition, the proportion of goblet
      cells containing acidic mucin increased 36 h after injection by 50% compared with
      the controls. The mucin mRNA expression increased gradually from d 17 of
      incubation to 3 d posthatch. Enhanced expression of the mucin mRNA was found at
      the day of hatch in chicks that received carbohydrate solution into the amnionic
      fluid in comparison with the control group. The results showed that providing the
      carbohydrates as an energy source to the late-term embryo had a trophic effect on
      the small intestine and enhanced goblet cell development.

PMID- 16615352
TI  - The vitamin D3 requirement of broiler breeders.
AB  - An experiment was conducted with 25- to 66-wk-old Ross broiler breeders in an
      environment excluding ultraviolet light to determine the cholecalciferol (D3)
      requirements for hen day egg production; hatchability; body weight of the progeny
      at 1 d; embryo mortality during the early (1 to 10 d of incubation), middle (11
      to 15 d of incubation), and late stages (16 to 21 d of incubation) of
      development; egg weight; specific gravity; and body ash of the progeny at 1 d of
      age. Five levels of vitamin D3 (125, 250, 500, 1,000, and 2,000 IU/kg of diet)
      were fed to hens from 25 to 66 wk of age. One additional group was fed no
      supplemental D3 until 36 wk of age and was then changed to 4,000 IU/kg of diet.
      Separate regression analyses were performed for wk 27 to 36 (peak original
      design) and for wk 37 to 66 (postpeak production modified design). The D3 levels
      for the predicted maximum hen day egg production during peak and postpeak were
      1,424 and 2,804 IU/kg, respectively. The D3 levels for the predicted maximum
      hatchability were 1,390 IU/ kg (peak) and 2,708 IU/kg (postpeak). The level of D3
      that resulted in the minimum early embryo mortality was 1,288 IU/kg at peak;
      however, no significant effect was observed at postpeak. The D3 levels for
      minimum middle stage embryo mortality were 1,130 IU/kg (peak) and 2,568 IU/kg
      (postpeak) and for late stage embryo mortality were 1,393 IU/kg (peak) and 2,756
      IU/kg (postpeak). The D3 level for maximum egg weight was 1,182 IU/kg (peak) and
      for specific gravity was 1,337 IU/kg (peak) and >2,000 IU/kg (postpeak). The D3
      level for maximum body ash of progeny at d 1 was >2,000 IU/kg. Analysis of the
      data from the original design of the experiment (treatments providing 0, 125,
      250, 500, 1,000, and 2,000 IU of vitamin D3/kg for the 27- to 36-wk-old birds)
      indicates a requirement of approximately 1,400 IU of D3/kg of feed for broiler
      breeder hens. When the data from the modified experiment (37 to 66 wk of age)
      include conversion of the treatment provided at 0 IU of D3/kg to a treatment
      providing 4,000 IU of D3/kg, the requirement may be approximately 2,800 IU of
      D3/kg.

PMID- 16615353
TI  - A multiple regression model approach to contrast the performance of 2-hydroxy-4
      methylthio butanoic acid and DL-methionine supplementation tested in broiler
      experiments and reported in the literature.
AB  - The purpose of this paper was to compile all available literature comparing the
      relative performance of 2-hydroxy-4-methylthio butanoic acid (HMTBA) with DL
      methionine (DLM) in broiler chickens and using multiple regression techniques, to
      estimate the predicted dose responses and relative performance of the 2 Met
      compounds for gain and feed conversion (FC). A database was developed that
      contained all available broiler studies in which HMTBA and DLM were both present
      in the same study; weight gain was recorded; Met addition, age of birds, and
      duration of study were defined; and an unsupplemented control treatment was
      present. Sixty-two references complied with these criteria and included 100
      experiments with 427 observations for HMTBA and 411 for DLM. Multiple regression
      analysis of the database was used to identify the experimental and dietary
      conditions that contributed to the gain and FC responses of each source of Met
      activity. All identified variables contributed similarly to each Met source
      prediction model and both gain and FC models described a quadratic dose response.
      Under the average conditions of the database, the predicted responses for gain
      and FC models did not significantly differ between HMTBA and DLM. However, a
      trend was observed (P < or = 0.1) for the peak gain response for HMTBA to be
      numerically greater than DLM, suggesting benefits of HMTBA over DLM in the region
      of supplementation that is commercially relevant. The experimental and
      nutritional conditions that contribute to the response to HTMBA and DLM were
      identified and are discussed in the paper. This statistical approach provided a
      means to summarize the results obtained from a multitude of studies conducted
      over the last 5 decades and has provided a meaningful estimate of the relative
      performance of the 2 sources of Met activity. The lack of differences between the
      2 predicted models under experimental and commercial conditions supports an
      overall conclusion of equal performance of DLM and HTMBA when compared on an
      equal molar basis.

PMID- 16615354
TI  - Use of axial X-ray microcomputed tomography to assess three-dimensional
      trabecular microarchitecture and bone mineral density in single comb white
      leghorn hens.
AB  - Axial x-ray microcomputed tomography is a cost-effective technique with the
      potential to assess bone mineral density (mg/cc) in both cortical and cancellous
      bone in Single Comb White Leghorn hens. The technique requires little sample
      preparation and involves relatively simple data processing. The system described
      in this research is based on compact fan-beam type tomography, using a tungsten
      anode x-ray tube with a relatively small focal spot (approximately 5 microm),
      coupled with a high-resolution x-ray detector system (approximately 10 microm).
      To produce a real 3-D data set using microcomputed tomography, x-ray projection
      views were acquired at 720 equally spaced angular positions (0.5 degrees) around
      the object of interest. These groups of views were then used to reconstruct a
      computed tomography image. A test grid with orthogonal test lines was used to
      calculate bone volume and bone surface. From these calculations, parallel plate
      equations were used to derive trabecular architectural parameters such as average
      trabecular plate thickness and average trabecular plate separation. Three
      dimensional microarchitecture was evaluated using specialized stereological
      analysis software. Significant relationships between apparent bone mineral
      density (mg/cc) and 3-D structure were observed in femoral specimens from 66-wk
      old Single Comb White Leghorn hens.

PMID- 16615355
TI  - Modulation of conjugated linoleic acid-induced loss of chicken egg hatchability
      by dietary soybean oil.
AB  - The main objective of the present study was to determine the minimum level of
      dietary plant oil supplementation that results in full recovery from loss of
      hatchability induced by conjugated linoleic acid (CLA). Another objective was to
      define the changes in egg yolk fatty acid composition associated with the loss
      and recovery of hatchability. Shaver hens were assigned to groups of 8 and were
      fed a diet containing either no CLA plus 0.5% soybean oil (control) or 0.5% CLA
      (1:1 mixture of cis-9, trans-11 and trans-10, cis-12 CLA) plus 0, 2, 4, 6, or 8%
      soybean oil for 15 d. Supplementation with CLA (CLA plus 0% soybean oil) resulted
      in complete loss of hatchability of fertile eggs. Hatchability was progressively
      improved by increasing doses of soybean oil, and full recovery of hatchability
      compared with the control levels was achieved at 6% soybean oil. There was no
      further improvement in hatchability when 8% soybean oil was added to the CLA
      supplemented diet. Loss of hatchability was associated with a 2- to 3-fold
      decrease in desaturase ratios (cis-9 C16:1/C16:0 and cis-9 C18:1/C18:0) in the
      egg yolk total lipids, indicating marked inhibition of delta-9 desaturase in the
      chicken liver. In addition, the concentration of arachidonic acid was observed to
      decrease. Recovery of hatchability was associated with an increased proportion of
      linoleic acid and linolenic acid in the egg yolk. However, there was no change in
      desaturase ratios, suggesting that delta-9 desaturase inhibition persisted.
      Increased incorporation of dietary linoleic and linolenic acids might have
      compensated for the reduced levels of palmitoleic and oleic acid, thus allowing
      for the improvement in hatchability.

PMID- 16615356
TI  - Responses of male growing broilers to increasing levels of balanced protein
      offered as coarse mash or pellets of varying quality.
AB  - Two experiments with 14- to 35-d-old male broilers were performed to investigate
      the interactions between increasing levels of balanced protein (BP; 9.7, 10.7,
      11.7, and 12.7 g of digestible Lys/kg of feed) and physical feed form. In
      Experiment 1 diets were offered as coarse mash and pellets of either good or poor
      quality. Good pellet quality was characterized by high durability. In Experiment
      2 diets were offered as good quality pellets or coarse mash. However, for the
      latter particle size, distribution either was kept constant with increasing BP or
      changed with increasing proportion of soybean meal. Feed intake generally
      decreased with increasing BP; however, feed intake was highest in good pellets
      fed to broilers and lowest in mash fed to birds. Although there was only a small
      response on weight gain in mash-fed birds, feed conversion improved substantially
      for all feed forms with increasing BP. Particle size distribution did not affect
      this effect. Highest weight gain was achieved with good pellets; to achieve
      similar performance with poor pellet quality, higher levels of BP were needed.
      Carcass evaluation suggested increasing breast meat yield and particularly
      decreasing fat accretion with increasing BP. Results of both experiments indicate
      that optimum dietary amino acid levels for growing broilers may vary among
      different physical feed forms.

PMID- 16615357
TI  - Diet-induced thermogenesis and glucose oxidation in broiler chickens: influence
      of genotype and diet composition.
AB  - The main objectives of this study were to explore the role of diet-induced
      thermogenesis in the regulation of voluntary feed intake and to determine the
      glucose oxidation of broiler chicken strains, known to differ in glucose-insulin
      balance. From 2 to 7 wk of age, male broiler chickens of a fat and a lean line
      were reared on 1 of 2 isoenergetic diets with constant gross energy and
      carbohydrate levels but with substitutions between fat and protein. The low
      protein (LP/HF) diet contained 126 g of protein/kg and 106 g of fat/kg, whereas
      the low fat (LF/HP) diet contained 242 g of protein/kg and 43 g of fat/kg. There
      was no significant effect of the genetic background of the broilers on the
      glucose oxidation rate (as measured by stable isotope breath test) or protein
      oxidation (as measured by plasma uric acid levels). Considering the difference in
      carcass composition (fat content) of both lines, this leads to the hypothesis
      that the lines differ predominantly in fat metabolism. Although there was no line
      effect on plasma triglyceride and free fatty acid concentrations, it was
      hypothesized that there might be differences in fat oxidation or de novo
      lipogenesis, or both, between the genotypes. Diet-induced thermogenesis per
      metabolic body weight (kg of BW0.75) per 24 h, expressed per gram of feed intake,
      was not significantly influenced by genetic background or by diet composition.
      Therefore, a model linking feed intake to diet-induced thermogenesis, as
      postulated for adult mammals, could not be corroborated for growing broiler
      chickens.

PMID- 16615358
TI  - Methionine requirements of male white Peking ducks from twenty-one to forty-nine
      days of age.
AB  - A dose-response experiment with 6 dietary methionine levels (0.20, 0.275, 0.35,
      0.425, 0.50, and 0.575%) was conducted with male White Peking ducklings to
      estimate the methionine requirement of growing ducks from 21 to 49 d of age. One
      day-old male White Peking ducklings were fed common starter diets from hatching
      to 21 d of age and then fed the experimental diets from 21 to 49 d of age. Three
      hundred thirty-six 21-d-old birds were allotted to 24 pens with 14 birds per pen
      according to similar pen weight. There were 6 dietary treatments, each containing
      4 replicate pens. At 49 d of age, weight gain, feed intake, and feed/gain of
      ducks from each pen were measured, and 2 ducks selected randomly from each pen
      were slaughtered to evaluate the yields of abdominal fat, breast meat (including
      pectoralis major and pectoralis minor), and leg meat (including thigh and drum
      stick). Significant effects of dietary methionine on weight gain, breast meat,
      and abdominal fat were observed. Both weight gain and breast meat yield showed
      significant quadratic response to increasing dietary methionine, and abdominal
      fat decreased linearly (P < 0.05). According to the quadratic model, the optimal
      methionine requirement of male White Peking ducks from 21 to 49 d of age for
      maximum weight gain and breast meat yield were 0.377 and 0.379%, respectively.

PMID- 16615359
TI  - Intestinal bacterial community and growth performance of chickens fed diets
      containing antibiotics.
AB  - This study was conducted to relate the performance of broiler chickens fed diets
      containing growth-promoting antibiotics to changes in the intestinal microbiota.
      The technique of denaturing gradient gel electrophoresis (DGGE) of amplicons of
      the region V3 of 16S rDNA was used to characterize the microbiota. Two
      experiments were conducted, one with broilers raised in battery cages and the
      other with broilers raised in floor pens. Antibiotics improved the performance of
      the chickens raised in floor pens only. Avilamycin, bacitracin methylene
      disalicylate, and enramycin induced changes in the composition of the intestinal
      bacterial community of the birds in both experiments. The number of bacterial
      genotypes found in the intestinal tract of chickens was not reduced by the
      antibiotics supplemented in either environment. However, the changes in the
      composition of the intestinal bacterial community induced by antibiotics may be
      related to improvement in growth performance. This was indicated by the
      suppression of 6 amplicons and the presence of 4 amplicons exclusive to the
      treatment that had the best performance in the floor pen experiment.

PMID- 16615360
TI  - The role of glucagon in regulating chicken hepatic malic enzyme and histidase
      messenger ribonucleic acid expression in response to an increase in dietary
      protein intake.
AB  - Increased dietary protein intake rapidly (3 h) decreases hepatic malic enzyme and
      increases hepatic histidase mRNA expression in broiler chicks. A series of
      experiments was conducted to determine the role that glucagon or a specific
      mixture of dietary amino acids might have in regulating the rapid changes in mRNA
      expression of these enzymes, when dietary protein intake is increased. Three
      hours after the injection of glucagon (240 microg/kg of BW) into the brachial
      vein of broiler chicks, hepatic malic enzyme mRNA expression was significantly
      lower and hepatic histidase mRNA expression was significantly greater than the
      level detected in saline-injected chicks. In addition, broiler chicks fed a high
      (40 g/ 100 g of diet) protein diet had significantly higher plasma glucagon
      levels at 1 and 3 h after initial access to this diet than broiler chicks fed a
      basal (22 g/100 g of diet) protein diet. The plasma glucagon concentration,
      however, was not different between the chicks fed the 2 dietary protein levels at
      2 h after the initial access to the 2 diets. When a mixture of indispensable or
      dispensable amino acids was added to the basal diet to equal the concentrations
      of the individual indispensable or dispensable amino acids in the high protein
      diet, hepatic mRNA expression of malic enzyme and histidase were intermediate to
      the expression found in chicks fed the basal and high protein diet. The results
      indicate that glucagon may mediate the changes in the mRNA expression of malic
      enzyme and histidase in response to dietary protein intake and that total amino
      acid intake rather than the ingestion of specific amino acids regulates the mRNA
      expression of malic enzyme and histidase in chicks.

PMID- 16615361
TI  - Physiological stress in laying hens.
AB  - Stress responses in laying hens were mediated by continuous infusion of
      adrenocorticotropin (ACTH) via osmotic pumps. The ACTH was dissolved in saline
      solution (0.85%), and each pump delivered 8 IU of ACTH per kilogram of BW per day
      at the rate of 1 microL/h for 7 d. Control hens received pumps loaded with
      saline. Measurements were made at 6 d postpump implantation, unless otherwise
      indicated. The ACTH-treatment increased BW and total carcass, rear half of
      carcass, intestinal, and liver weights. Proximate analyses of liver showed
      increases in dry weight, moisture, protein, fat, carbohydrate, and ash content.
      Weights of the front half of the carcass, as well as weights of the abdominal fat
      pad, heart, head, feet, and skin were unaffected by ACTH-treatment. Plasma
      corticosterone, glucose, cholesterol, and high-density lipoproteins were
      increased by ACTH, whereas triglycerides were decreased. Feed and water intake,
      total excreta, and excretory DM were all increased in ACTH-treated hens. The ACTH
      decreased carbohydrate in excreta, whereas ash, protein, fiber, and gross energy
      of excreta were unaffected. The ACTH did not affect digestibility of dry matter,
      proteins, carbohydrates, fats, or gross energy; however, absorption of ash,
      protein, carbohydrates, and gross energy were increased by ACTH. Antibody levels
      to sheep red blood cells, cell-mediated immunity (wattle index to
      phytohemagglutinin-phosphate), and relative spleen weight were reduced by ACTH,
      whereas heterophil:lymphocyte ratio was increased. Reproduction in hens was
      negatively affected by ACTH treatment, as measured by cessation of laying on the
      third day of treatment, atretic follicles, and decreased oviduct weight.

PMID- 16615362
TI  - Effect of egg size on heat production and the transition of energy from egg to
      hatchling.
AB  - An experiment was conducted to study the effect of egg size on embryo
      development, heat production, and energy partitioning between egg and hatchling.
      Small (56.1 +/- 0.12 g SEM) and large (70.0 +/- 0.11 g SEM) hatching eggs were
      incubated in climate respiration chambers, and eggshell temperature was
      maintained constant at 37.8 degrees C in both egg weight classes by adjusting
      machine temperature. Dry matter, ash, protein, and fat contents were determined
      in albumen, yolk, yolk-free body (YFB), and residual yolk (RY), and carbohydrate
      contents and caloric values were calculated. To achieve a constant eggshell
      temperature, machine temperature needed to be set lower from d 15 onward,
      coinciding with increased heat production in large eggs compared with small eggs.
      Selective nutrient uptake resulted in higher fat content and lower protein
      content in RY in chicks that hatched from small eggs compared with large eggs.
      The respiration quotient in small and large eggs was the same, and embryos in
      small and large eggs were equally efficient in the transfer of energy from egg to
      YFB. The surplus availability of nutrients in large eggs was therefore held
      responsible for the absolute and relative higher weight of RY in chicks that
      hatched from large eggs compared with small eggs.

PMID- 16615363
TI  - Evaluation of the serotonin receptor blockers ketanserin and methiothepin on the
      pulmonary hypertensive responses of broilers to intravenously infused serotonin.
AB  - The pathogenesis of pulmonary hypertension remains incompletely understood. Many
      factors have been implicated; however, there has been great interest in the
      potent pulmonary vasoconstrictor serotonin (5-HT) due to episodes of primary
      pulmonary hypertension in humans triggered by serotoninergic appetite-suppressant
      drugs. Pulmonary hypertensive patients have elevated blood 5-HT levels and
      pulmonary vasoconstriction induced by 5-HT is believed to be mediated through 5
      HT1B/1D and 5-HT2A receptors that are expressed by pulmonary smooth muscle cells.
      The vascular remodeling associated with pulmonary hypertension also appears to
      require the serotonin transporter. We investigated the roles of 5-HT receptor
      blockers on the development of pulmonary hypertension induced by infusing 5-HT
      i.v. in broilers. For this purpose, we treated broilers with the selective 5-HT2A
      receptor antagonist ketanserin (5 mg/ kg of BW) or with the nonselective 5-HT1/2
      receptor antagonist methiothepin (3 mg/kg of BW). Receptor blockade was followed
      by infusion of 5-HT while recording pulmonary arterial pressure and pulmonary
      arterial blood flow. The results demonstrate that methiothepin, but not
      ketanserin, eliminated the 5-HT-induced pulmonary hypertensive responses in
      broilers. The 5-HT2A receptor does not, therefore, appear to play a role in the 5
      HT-induced pulmonary hypertensive responses in broilers. Methiothepin did not
      inhibit pulmonary vascular contractility per se, because the pulmonary
      hypertensive response to the thromboxane A2 mimetic U44069 remained intact in
      methiothepin-treated broilers. Methiothepin will be a useful tool for evaluating
      the role of 5-HT in the pathogenesis of pulmonary hypertension syndrome (ascites)
      as well as the onset of pulmonary hypertension triggered by inflammatory stimuli
      such as bacterial lipolysaccharide.

PMID- 16615364
TI  - Biochemical survey on episodic localized darkening in turkey deboned thigh meat
      packaged in modified atmosphere.
AB  - The color of food, especially meat and meat products, is a parameter that
      strongly influences consumer choice. In Italy, repeated cases of darkening in
      deboned thigh meat of male turkeys packaged in modified atmosphere (MAP; 80% 02,
      20% CO2) have been reported. The pH, lipid oxidation (TBARS), heme proteins, and
      iron content were investigated in MAP samples of turkey males, females, and in
      oxygen-permeable film-packaged males. Furthermore, the absorbance spectrum (400
      to 700 nm) of the meat extracts was analyzed to better delineate the evolution
      and characteristics of the darkening process. Results showed that darkening
      occurred only in males with higher content of total iron, independently of the
      content of heme proteins, which differs only between males and females.
      Furthermore, pH was higher in muscles taken as controls, with respect to muscles
      involved in the darkening, as well as in females. Finally, TBARS values were
      found to be higher in darkened regions than in not darkened ones, as well as in
      MAP samples with respect to oxygen-permeable film-packaged samples. These
      findings suggest that darkening occurrence might depend on kind of muscle, sex,
      and individual characteristics of the animals raised under the same breeding
      conditions.

PMID- 16615365
TI  - Comparison of Gompertz and neural network models of broiler growth.
AB  - Neural networks offer an alternative to regression analysis for biological growth
      modeling. Very little research has been conducted to model animal growth using
      artificial neural networks. Twenty-five male chicks (Ross x Ross 308) were raised
      in an environmental chamber. Body weights were determined daily and feed and
      water were provided ad libitum. The birds were fed a starter diet (23% CP and
      3,200 kcal of ME/kg) from 0 to 21 d, and a grower diet (20% CP and 3,200 kcal of
      ME/ kg) from 22 to 70 d. Dead and female birds were not included in the study.
      Average BW of 18 birds were used as the data points for the growth curve to be
      modeled. Training data consisted of alternate-day weights starting with the first
      day. Validation data consisted of BW at all other age periods. Comparison was
      made between the modeling by the Gompertz nonlinear regression equation and
      neural network modeling. Neural network models were developed with the Neuroshell
      Predictor. Accuracy of the models was determined by mean square error (MSE), mean
      absolute deviation (MAD), mean absolute percentage error (MAPE), and bias. The
      Gompertz equation was fit for the data. Forecasting error measurements were based
      on the difference between the model and the observed values. For the training
      data, the lowest MSE, MAD, MAPE, and bias were noted for the neural-developed
      neural network. For the validation data, the lowest MSE and MAD were noted with
      the genetic algorithm-developed neural network. Lowest bias was for the neural
      developed network. As measured by bias, the Gompertz equation underestimated the
      values whereas the neural- and genetic-developed neural networks produced little
      or no overestimation of the observed BW responses. Past studies have attempted to
      interpret the biological significance of the estimates of the parameters of an
      equation. However, it may be more practical to ignore the relevance of parameter
      estimates and focus on the ability to predict responses.

PMID- 16615366
TI  - Comparison of forecasting methodologies using egg price as a test case.
AB  - Egg price forecasting of shelled eggs is a complex problem. Traditionally, future
      egg price has been predicted using a combination of regression analysis and
      experienced-based intuition to build a model, which is then fine-tuned to
      prevalent market conditions. Even after collecting reliable and expensive data,
      the subsequent analysis, in many cases, does not produce a high confidence to
      explain the variations in egg price. In the current project, a different approach
      using neural networks was used to forecast egg price. A neural network is a
      mathematical model of an information-processing structure that is loosely based
      on our present understanding of the working of human brain. An artificial neural
      network consists of a large number of simple processing elements connected to
      each other in a network. Urner Barry egg quotes from 1991 to 2002 as well as
      number of hens, egg storage capacity, and number of eggs placed for hatching from
      the USDA databases (1993 to 2000) were used to forecast egg price. Regression
      analysis explained only 37% of the variation in egg price due to the above
      mentioned 3 factors. Neural networks, on the other hand, recognize the pattern in
      previous years' egg prices and then predict the future price more efficiently.
      The 3 networks used in this research (Ward, back-propagation, and general
      regression neural networks) fit the forecast line more tightly to the previous
      year's egg price line than did regression analysis. In the case of general
      regression neural networks, the R2 value was as high as 60%. Results suggest that
      neural networks may be a more reliable method of egg price forecasting than
      simple regression analysis if reliable data are collected and manipulated for
      such models.

PMID- 16615367
TI  - Broiler short-term feed preferences measured with SRAbox, a new feed choice
      procedure.
AB  - Three dietary compositions and 3 methods of pellet preparation were used in
      different choice situations to improve our understanding of the factors perceived
      by broiler chickens in the physical structure of their diet. Within the same
      visual field, broiler chickens were offered 8 microfeeders containing different
      pelleted feeds that could be reached from the same position of the bird. Chickens
      were daily tested during 5-min tests following a 45-min period of feed
      withdrawal, after adaptation to individual cages and experimental feeders. Two
      feeds (4 microfeeders/feed in alternate positions) were weighed prior to and
      after the test. Behavior of the chickens was videotaped during the test to count
      the number of pecks given to each microfeeder. In a first experiment, 2 feeds of
      distinct composition were either steam or cold-pelleted. The tests of choice were
      repeated daily from 22 to 25 and from 35 to 38 d of age on 96 male broiler
      chickens. Significant preferences were measured from the first test. Similar
      preferences were measured when chickens received the same choice or alternating
      choices from one test to another. Differences of feed intake between 2 feeds
      during 5 min were significantly correlated to differences of number of pecks (R2
      = 0.85). In most cases, preferences were established within the first minute of
      pecking. Steam pellets were significantly preferred to cold pellets for one feed
      composition but not for the other. Preferences for compositions were consistent
      whatever the pellet preparation and probably associated with the color of the
      feeds. A second experiment confirmed that 38-d-old broiler chickens seemed to
      prefer light colors. Short-term preferences of a chicken for a feed were rather
      influenced by physical characteristics of feed particles (size, color, hardness)
      than by the origin of raw materials. Feed pecking may change because of feed
      composition itself, because of its consequences on color or texture cues, or
      both.

PMID- 16615368
TI  - General anesthesia or chemical restraint?

PMID- 16615369
TI  - Hand-over-mouth: another perspective.

PMID- 16615370
TI  - Utilization of a hospital for treatment of pediatric dental emergencies.
AB  - PURPOSE: The purpose of this study was to investigate dental emergencies treated
      at a hospital clinic and emergency department (ED) to: (1) analyze emergency
      types; (2) determine reasons for seeking hospital care; and (3) examine trends
      compared to previous studies from this institution. METHODS: Records of 2,683
      emergencies from 1995 to 2003 were reviewed. Demographics, reason for seeking
      care, and treatment details were analyzed overall by emergency type and for
      subgroups of patients with severe early childhood caries (S-ECC) and patients
      referred from other EDs. RESULTS: Emergencies were: 51% trauma, 40% caries, and
      9% "other" emergencies unrelated to trauma or caries. Common patient
      characteristics were: (1) young age; (2) non-Caucasian ethnicity; (3) Medicaid as
      payer; (4) no dentist; and (5) proximity to the hospital. Caries emergencies
      increased significantly over the study period (P = .008), and 22% had S-ECC.
      Patients referred from other EDs were: 11% of trauma patients who commonly
      required sutures and/or extractions; and 3% of caries patients, 82% with
      extraoral swelling. CONCLUSIONS: Characteristics of patients seeking hospital
      care for dental emergencies were: (1) young age; (2) non-Caucasian ethnicity; (3)
      Medicaid as payer; (4) no dentist; and (5) proximity to CHRMC. Use differed by
      ethnic groups: Caucasians presented mostly for trauma; African Americans
      presented equally for caries and trauma; and Hispanics and Asians presented
      primarily for caries. Access to care, caries, and severe early childhood caries
      remain significant problems despite multiple programs targeting children's' oral
      health in Washington State.

PMID- 16615371
TI  - Childhood obesity and dental development.
AB  - PURPOSE: The purpose of this study was to determine if increased body mass index
      (BMI) is associated with accelerated dental development in children ages 8 to 15.
      METHODS: The dental development ages of 104 children were determined using the
      Demirjian method and panoramic radiographs. Using the system developed by the
      International Obesity Task Force, BMI status was determined for each subject (63
      normal weight, 23 overweight, and 18 obese subjects). The difference between
      chronologic age and dental age was analyzed against BMI, age, and gender using 3
      way analysis of variance. RESULTS: Dental development was significantly
      accelerated with increased BMI, even after adjusting for age and gender (P <
      .01). The mean difference between chronologic and dental age among all subjects
      was 0.68 +/- 1.31 years. The mean dental age acceleration for overweight and
      obese subjects was 1.51 +/- 1.22 years and 1.53 +/- 1.28 years, respectively.
      CONCLUSIONS: Children who were overweight or obese had accelerated dental
      development, even after adjusting for age and gender. Accelerated dental
      development in obese children is an important variable to consider in pediatric
      dental and orthodontic treatment planning where timing is crucial.

PMID- 16615372
TI  - Association between childhood obesity and smooth-surface caries in posterior
      teeth: a preliminary study.
AB  - PURPOSE: The purpose of this study was to determine if increased body mass index
      (BMI) is associated with an increased risk for dental caries. METHODS: Caries
      severity averages were calculated for a convenience sample of 178 children, ages
      8 to 11 years, who participated in the University of Louisville Dental School
      based dental treatment program "Smile Kentucky." Caries severity averages were
      then analyzed against the children's BMI, with gender and age used as covariates.
      RESULTS: The mean caries average for permanent molars significantly increased
      with increased BMI, even after adjusting for age and gender. The mean overall
      caries average did not vary significantly with patient age, BMI, or gender and
      may be due to confounding mixed dentition events such as eruption, extraction,
      variable teeth exfoliation, etc. CONCLUSIONS: Elevated body mass index is
      associated with an increased incidence of permanent molar interproximal caries.

PMID- 16615373
TI  - Effectiveness of various modes of computerized delivery of local anesthesia in
      primary maxillary molars.
AB  - PURPOSE: The purpose of this study was to compare the effectiveness of
      infiltration and intrasulcular injection, delivered by a computerized delivery
      system (CDS), to primary maxillary molars. METHODS: The study population
      consisted of 178 children (2-14 years old) who received local infiltration
      (buccal and palatal) or intrasulcular injection to primary maxillary molars with
      the use of a CDS. Behavior was managed using: (1) behavioral management
      techniques; (2) N2O inhalation; or (3) sedation. Measured dependent variables
      included the: (1) child's subjective perception of well-being before and
      immediately after anesthesia (scale = 0-100); (2) child's pain behavior during
      anesthesia, as measured by Children's Hospital of Eastern Ontario pain scale
      (CHEOPS; range = 4-13); and (3) effectiveness of anesthesia during dental
      treatment. RESULTS: Low stress levels were shown for most children before and
      immediately after anesthesia (range = 12-23). The CHEOPS rating for pain
      distractive behavior associated with palatal and buccal infiltration and
      intrasulcular anesthesia by CDS was similar (6.0 +/- 1.9, 5.8 +/- 1.7, and 5.9 +/
      1.6, respectively). Children treated under sedation, compared to behavioral
      management techniques, showed higher CHEOPS scores (P = .004). The effectiveness
      of anesthesia using a CDS (infiltration and intrasulcular) had a downward trend,
      but was not significantly different for restoration (91%), pulpotomy and
      preformed crowns (79%), or extraction (74%; mean = 86%). There was no significant
      difference between infiltration and intrasulcular effectiveness or for age,
      gender, or tooth location (primary maxillary first vs second molars).
      CONCLUSIONS: CDS caused low levels of stress and pain reaction after palatal
      infiltration equal to that for buccal infiltration. All procedures achieved
      anesthesia effectiveness (86%), with no differences between primary maxillary
      first and second molars.

PMID- 16615374
TI  - Clinical evaluation of root canal obturation methods in primary teeth.
AB  - PURPOSE: This study evaluated in vivo 2 different obturation techniques (lentulo
      spiral mounted in a slow-speed handpiece and hand-held) in primary teeth.
      METHODS: The study was carried out on 24 children (mean age = 6.71 years) who had
      received 50 single-visit zinc oxide and eugenol (ZOE) pulpectomies in primary
      molars. The root canal filling materials were deposited into the canals either by
      a lentulo spiral mounted in a slow-speed handpiece or by a hand-held lentulo
      spiral. Evaluation of pulpectomized molars was performed by both authors
      immediately and 6 months following treatment using specific clinical and
      radiographic criteria. In cases of disagreement, the lower rank was selected.
      RESULTS: The study found 64% (16/25) optimal filling (if 1 or more of the canals
      having ZOE ended at the radiographic apex or up to 2 mm short of the apex) when
      the lentulo spiral mounted in the slow-speed handpiece was used. It also found a
      96% (21/22) clinical success rate in the group obturated by the lentulo spiral
      mounted in a slow-speed handpiece vs 48% (12/25) optimal filling and a 92%
      (23/25) clinical success rate in the group obturated by a hand-held lentulo
      spiral. The radiographic success for over- and optimally filled canals, when
      combining both lentulo groups, was significantly greater than underfilled root
      canals (P = .009). CONCLUSIONS: There was no statistically significant difference
      between the 2 techniques of obturation, according to the quality of the root
      canal filling or success rate.

PMID- 16615375
TI  - SEM and microleakage evaluation of 3 flowable composites as sealants without
      using bonding agents.
AB  - PURPOSE: The aim of this study was to determine if flowable composites can be
      used as pit and fissure sealants without bonding agents. METHODS: Three flowable
      composites (Filtek Flow, Tetric Flow, Charmfil Flow) and a filled sealant
      (Ultraseal XT Plus) were used. The patterns of resin tag formation in the 4
      sealant materials were compared using scanning electron microscopy. For the
      microleakage assessment, 54 extracted human premolar teeth were randomly divided
      into 3 groups. In each group, a conventional filled sealant and 1 of the 3
      flowable composites were applied to occlusal fissures. The teeth were
      thermocycled and immersed in a 1% methylene blue solution for 48 hours. Each
      tooth was sectioned and examined to determine the extent of dye penetration.
      RESULTS: Three flowable composites and a filled sealant showed a similar resin
      tag formation pattern. The 3 flowable composites showed significantly more
      microleakage in each group than the filled sealant. The level of microleakage was
      similar in the 3 flowable composites. CONCLUSIONS: Concerning the microleakage
      data, use of the filled sealant is more effective in sealing mechanically
      prepared occlusal fissures in comparison to the flowable composites.

PMID- 16615376
TI  - Incontinentia pigmenti: a case report.
AB  - Incontinentia pigmenti (IP) is a genodermatosis with an X-linked dominant mode of
      inheritance, characterized by ectodermal, mesodermal, neurological, ocular, and
      dental manifestations. The purpose of this case study was to report the oral and
      dental manifestations of an IP case in a Venezuelan pediatric patient. A 9 year
      old Venezuelan girl was evaluated. She showed macular pigmented lesions in her
      face, trunk, back, legs, and fingers as well as abnormal hair distribution,
      alopecia on the vertex, and hypoplasia of eyebrows. During the dental
      examination, conical shaped-teeth and delayed dental eruption was evidenced. The
      microanalytical examination showed dentin without significant alterations in the
      mineralization except for hypermineralization in focal areas. In addition, a
      decrease in the enamel mineralization was observed.

PMID- 16615377
TI  - A longitudinal controlled study of factors associated with mutans streptococci
      infection and caries lesion initiation in children 21 to 72 months old.
AB  - PURPOSE: The purpose of this longitudinal study was to determine factors
      associated with mutans streptococci (MS) infection and development of caries
      lesions in a group of children 21 to 72 months old. METHODS: The 63 caries-free
      children, recruited since birth, were divided into: (1) a study group of 24
      children who were colonized with MS; and (2) a control group of 39 children
      without MS. The children were recalled every 3 months for approximately 24
      months, and their social, medical, and dental histories were updated. At each
      recall, the teeth were checked for presence or absence of plaque, enamel
      hypoplasia, and caries lesions, and their MS status was assessed using a
      commercial test kit. RESULTS: MS infection was associated with: (1) visible
      plaque (P < .01); (2) enamel hypoplasia (P < .05); (3) commencement of tooth
      brushing after 12 months of age (P < .05); (4) lack of parental assistance with
      tooth-brushing (P < .025); and (5) increased hours of child care/school (P <
      .05). Four children (20%) were colonized at an age range of 21 to 36 months, 9
      (45%) at 37 to 48 months, and 7 (35%) at 49 to 72 months (P < .001). Eight
      children who developed caries lesions: (1) had more hypoplastic teeth (P < .001);
      (2) ate sugar-containing snacks (P < .05); and (3) did not brush regularly with
      chlorhexidine gel (P < .01) compared to those who remained free of caries
      lesions. CONCLUSIONS: Lack of oral hygiene, consumption of sugar-containing
      snacks, and enamel hypoplasia are significant factors for both MS infection and
      caries lesion initiation.

PMID- 16615378
TI  - Assessment of the quality of reporting observational studies in the pediatric
      dental literature.
AB  - PURPOSE: The purpose of this assessment was to evaluate reporting of
      observational studies in the pediatric dental literature. METHODS: This
      assessment included the following steps: (1) developing a model for reporting
      information in clinical dentistry studies; (2) identifying treatment comparisons
      in pediatric dentistry that were evaluated by at least 5 observational studies;
      (3) abstracting from these studies any data indicated by applying the reporting
      model; and (4) comparing available data elements to the desired data elements in
      the reporting model. RESULTS: The reporting model included data elements related
      to: (1) patients; (2) providers; (3) treatment details; and (4) study design. Two
      treatment comparisons in pediatric dentistry were identified with 5 or more
      observational studies: (1) stainless steel crowns vs amalgams (10 studies); and
      (2) composite restorations vs amalgam (5 studies). Results from studies comparing
      the same treatments varied substantially. Data elements from the reporting model
      that could have explained some of the variation were often reported inadequately
      or not at all. CONCLUSIONS: Reporting of observational studies in the pediatric
      dental literature may be inadequate for an informed interpretation of the
      results. Models similar to that used in this study could be used for developing
      standards for the conduct and reporting of observational studies in pediatric
      dentistry.

PMID- 16615379
TI  - Parental health literacy and children's dental health: implications for the
      future.
AB  - Health literacy--or the lack thereof--is now seen as a major impediment to the
      successful implementation of many health programs. Every day, parents make
      decisions, take actions, and consider issues that influence not only their own
      health, but also that of their children. Unfortunately, it is just being
      recognized that the reading skills of a significant proportion of American adults
      are below what is necessary to understand most of the educational materials they
      are provided. Without the ability to read these materials, parents lack the
      possibility of understanding the materials and implementing any recommendations
      to prevent or treat disease. The goal of this paper was to introduce pediatric
      dentists to the scope of the problem and acquaint them with some of the efforts
      they can undertake to promote health literacy in their own practices.

PMID- 16615380
TI  - The visual-auditory color-word stroop asymmetry and its time course.
AB  - Four experiments examined crossmodal versions of the Stroop task in order (1) to
      look for Stroop asymmetries in color naming, spoken-word naming, and written-word
      naming and to evaluate the time course of these asymmetries, and (2) to compare
      these findings to current models of the Stroop effect. Participants named color
      patches while ignoring spoken color words presented with an onset varying from
      300 msec before to 300 msec after the onset of the color (Experiment 1), or they
      named the spoken words and ignored the colors (Experiment 2). A secondary visual
      detection task assured that the participants looked at the colors in both tasks.
      Spoken color words yielded Stroop effects in color naming, but colors did not
      yield an effect in spoken-word naming at any stimulus onset asynchrony. This
      asymmetry in effects was obtained with equivalent color- and spoken-word-naming
      latencies. Written color words yielded a Stroop effect in naming spoken words
      (Experiment 3), and spoken color words yielded an effect in naming written words
      (Experiment 4). These results were interpreted as most consistent with an
      architectural account of the color-word Stroop asymmetry, in contrast with
      discriminability and pathway strength accounts.

PMID- 16615381
TI  - When the visual format of the color carrier word does and does not modulate the
      stroop effect.
AB  - We investigated the impact of making the color carrier word visually unfamiliar
      via case and font mixInG in the context of three Stroop experiments. Experiment 1
      yielded an increase in the size of the Stroop effect when the color carrier words
      were visually unfamiliar relative to lowercase words that were case and font
      consistent. Experiments 2A and 2B showed that the modulation of the Stroop effect
      by visual familiarity observed in Experiment 1 was eliminated when there was no
      correlation between the color and the color carrier word. These results are
      considered in the light of four different theoretical accounts of the Stroop
      effect (strength of association [Cohen, Dunbar, & McClelland, 19901, instance
      [Logan, 1988], schema [MacLeod, 2000], and obligatory processing followed by
      deactivation [Coltheart, Woollams, Kinoshita, & Perry, 1999]). None of these
      accounts appear capable of explaining all the results.

PMID- 16615382
TI  - Eye movements and the identification of spatially ambiguous words during chinese
      sentence reading.
AB  - Readers of Chinese must generally determine word units in the absence of visually
      distinct inter-word spaces. In the present study, we examined how a sequence of
      Chinese characters is parsed into words under these conditions. Eye movements
      were monitored while participants read sentences with a critical four-character
      (C1234) sequence. Three partially overlapping character groupings formed legal
      words in the ambiguous condition (C12, C23, and C34), two of which corresponded
      to context-consistent words (C12 and C34). Two nonoverlapping groupings
      corresponded to legal words in the control conditions (C12 and C34). In two
      experiments, readers spent more time viewing the critical character sequence and
      its two center characters (C23) in the ambiguous condition. These results argue
      against the strictly serial assignment of characters to words during the reading
      of Chinese text.

PMID- 16615383
TI  - When goals collide: monitoring the goals of multiple characters.
AB  - Most story plots contain multiple characters who are independent, interact, and
      often have conflicting goals. One would expect that narrative understanding would
      require monitoring of the goals, concerns, and situations of multiple agents.
      There is considerable evidence that understanders monitor the primary
      protagonist's goal plans (e.g., Suh & Trabasso, 1993). However, there is
      relatively little research on the extent to which understanders monitor the goals
      of multiple agents. We investigated the impact of characters' roles and
      prominence on the extent to which understanders monitor the goal plans of
      multiple characters in a feature length film. In Experiment 1, participants made
      situation change judgments, and in Experiment 2, they verbally described scenes.
      Both types of judgments indicated that viewers monitor the goals and plans of
      multiple agents but do so to a greater extent for characters more prominent to
      the plotline.

PMID- 16615384
TI  - Trial order and retention interval in human predictive judgment.
AB  - The influences of order of trial type and retention interval on human predictive
      judgments were assessed for a cue that was reinforced on half of its training
      presentations. Subjects observed 10 cue-outcome presentations (i.e., reinforced
      trials) and 10 cue-alone presentations (i.e., nonreinforced trials) in one of
      three different orders: all nonreinforced trials followed by all reinforced
      trials(latent inhibition), reinforced and nonreinforced trials interspersed
      (partial reinforcement), or al lreinforced trials followed by all nonreinforced
      trials (extinction). Ratings were based mainly on the most recent event type
      (i.e., a recency effect) when the test occurred immediately after training but
      were based mainly on initial event types (i.e., a primacy effect) when the test
      occurred after a 48-h delay. The subjects tested both immediately and with a long
      retention interval did not exhibit this shift to primacy (i.e., the recency
      effect persisted). These results demonstrate noncatastrophic forgetting and the
      flexible use of trial order information in predictive judgments.

PMID- 16615385
TI  - Expertise in ill-defined problem-solving domains as effective strategy use.
AB  - Expertise consists of many different cognitive structures. Lemaire and Siegler
      (1995) have proposed a four-layered account of expertise from a strategies
      perspective: Experts have better strategies, tend to use strategies that are
      better overall more often, are better able to select the circumstances to which a
      strategy best applies, and are better able to execute a given strategy.
      Originally, this account came from work in simple, well-defined domains. We
      explored this account in the complex, ill-defined domain of platoon leadership.
      In Experiment 1A, we elicited free-text responses to leadership scenarios from
      novices, intermediates, and experts, finding expertise effects for strategy base
      rates and choice, but not for strategy existence or the number of strategies
      used. In Experiment 1B, we used a new group of experts to gather ratings of the
      execution accuracy of the responses in Experiment 1A and found expertise
      differences in the ability to execute the same strategies. We propose several
      elaborations to the original four-layered strategies account of expertise on the
      basis of these results.

PMID- 16615386
TI  - Associative and causal reasoning accounts of causal induction: symmetries and
      asymmetries in predictive and diagnostic inferences.
AB  - Associative and causal reasoning accounts are probably the two most influential
      types of accounts of causal reasoning processes. Only causal reasoning accounts
      predict certain asymmetries between predictive (i.e., reasoning from causes to
      effects) and diagnostic (i.e., reasoning from effects to causes) inferences
      regarding cue-interaction phenomena (e.g., the overshadowing effect). In the
      experiments reported here, we attempted to delimit the conditions under which
      these asymmetries occur. The results show that unless participants perceived the
      relevance of causal information to solving the task, predictive and diagnostic
      inferences were symmetrical. Specifically, Experiments 1A and 1B showed that
      implicitly stressing the relevance of causal information by having participants
      review the instructions favored the presence of asymmetries between predictive
      and diagnostic situations. In addition, Experiment 2 showed that explicitly
      stressing the relevance of causal information by stating the importance of the
      causal role of events after the instructions were given also favored the
      asymmetry.

PMID- 16615387
TI  - How bad is a 10% chance of losing a toe? Judgments of probabilistic conditions by
      doctors and laypeople.
AB  - We presented a Web questionnaire to 139 physicians and medical researchers and
      109 laypeople. The subjects made judgments of badness and importance of
      prevention for eight medical conditions at each of seven different probability
      levels. By assuming that the response to each of the 56 risks was monotonically
      related to transformations of the probability and of the disutility of the
      condition, we could assess the relative effect of probability and disutility on
      each subject's judgments. Physicians' judgments were more sensitive than
      laypeople's judgments to changes in probability. Older and female laypeople were
      less sensitive to probability (and correspondingly, more responsive to
      differences in severity among medical conditions). Laypeople varied more than
      physicians in their responsiveness to probability. These results point to general
      individual differences in the effect of probability on evaluations of medical
      risks. They may also provide insight into causes and noncauses of physician
      patient miscommunication.

PMID- 16615388
TI  - The modality effect in false recognition: evidence for test-based monitoring.
AB  - False recognition in the Deese/Roediger-McDermott (DRM) paradigm has been shown
      to be greater following auditory study than following visual study, but there are
      competing explanations for this effect. We generalized this phenomenon in
      Experiment 1, finding an equivalent modality effect for associative (DRM) lists
      and categorized lists. Because conscious generationand subsequent monitoring of
      related lures during study is infrequent for categorized lists, this result is
      inconsistent with the idea that the modality effect is due to a study-based
      monitoring process. An alternative explanation is that visual study impairs
      relational processing relative to auditory study, which could cause a modality
      effect by lowering false recognition of related lures. We tested this idea in
      Experiment 2, by switching to a meaning-based test that is sensitive only to the
      retrieval of relational information. A modality effect was not obtained for
      either type of list on this test. The results from both experiments were
      predicted by a test-based monitoring account, rather than by the study-based
      monitoring or relational processing accounts.

PMID- 16615389
TI  - When do false memories cross language boundaries in English-Spanish bilinguals?
AB  - To determine whether false memories cross language boundaries, we presented
      English-Spanish bilinguals with conceptually related word lists for five study
      test trials. Some lists were heard in English, some in Spanish, and they were
      then followed by a recognition memory test composed of studied words,
      conceptually related nonstudied critical words, and unrelated words presented in
      the same language used at study or in a different language. Even though
      participants were instructed to recognize only previously heard words, they
      falsely recognized both same-language and different-language critical words. With
      practice, participants increased their accurate recognition of list words and
      decreased their false recognition of critical words when the study-test language
      was the same, and they decreased their false recognition of list words and
      critical words when the language differed. False memories can cross language
      boundaries when participants rely on conceptual representations from the word
      lists, but these errors decrease over trials as participants increasingly rely on
      language-specific lexical representations.

PMID- 16615390
TI  - Recollection rejection: gist cuing of verbatim memory.
AB  - Recollection rejection allows people to avoid accepting related lures presented
      on recognition tests by recollecting their instantiating study items. Two
      predictions made by fuzzy trace theoristswere tested. First, recollection
      rejection should likely occur when verbatim traces are available for retrieval.
      Second, related lures that closely approximate the gist of their instantiating
      study items should be more likely to evoke recollection rejection than related
      lures that do not provide such a match. In support of the first condition,
      estimates of recollection rejection were lower when participants studied items
      under divided as opposed to full attention. In support of the second prediction,
      estimates of recollection rejection were greater when participants were presented
      with antonyms as related lures, as opposed to rhymes. The present results
      contribute to the cued recall and recognition literatures by demonstrating that
      recollection rejection is moderated by similar factors as is cued recall.

PMID- 16615391
TI  - Retrieval-induced forgetting in recall and recognition of thematically related
      and unrelated sentences.
AB  - In three experiments, we assessed the effects of type of relation and memory test
      on retrieval-induced forgetting of facts. In Experiments 1 and 2, eight sets of
      four shared-subject sentences were presented for study. They were constructed so
      that half were thematically related and half were unrelated. A retrieval practice
      phase required participants to recall a subset of the studied sentences. In the
      final test, the participants were prompted to recall all the sentences (character
      cued in Experiment 1 and character plus stem cued in Experiment 2). The results
      showed that the retrieval-induced forgetting (RIF) effect was similar for
      thematically related and unrelated sentences, indicating that the presence of
      episodic relations among the sentences was sufficient to produce the effect. In
      Experiment 3, a recognition task was introduced and the RIF effect emerged in
      accuracy as well as in latency measures. The presence of this effect with item
      specific cues is difficult to accommodate for noninhibitory theories of
      retrieval.

PMID- 16615392
TI  - Verbal facilitation of face recognition.
AB  - We examined the effects of verbally describing a face on face memory, as assessed
      in an old/new recognition task. Experiment 1 established that describing faces
      facilitated their later recognition. In Experiment 2, we argue that verbalization
      facilitated the recognition of faces that had been previously described, but not
      of faces intermingled with the described faces. In Experiment 3, the participants
      described (or did not, in the control condition) either differences or
      similarities between pairs of faces. Verbal facilitation was equivalent for both
      types of descriptions. Finally, in Experiment 4, the participants were instructed
      to generate either holistic or featural descriptors. Verbal facilitation was
      equivalent for both types of descriptors. We discuss these findings in terms of
      the nature of the verbalization that benefits face recognition.

PMID- 16615393
TI  - Skill training, retention, and transfer: the effects of a concurrent secondary
      task.
AB  - In two experiments, we examined training, retention, and transfer of a duration
      production skill in a prospective paradigm. Participants were trained with
      feedback and then were either tested immediately for transfer without feedback or
      retrained with feedback 1 week later. There were three training and retraining
      conditions, two involving secondary tasks. Retention of the duration production
      skill was perfect across the 1-week delay when the secondary task condition was
      unchanged, but there was no skill transfer when that condition was changed. These
      findings demonstrate specificity of training, with the assumption that the
      cognitive operations learned during duration production training incorporate
      requirements of the secondary task. More generally, this study challenges the
      current practice in which training conditions often do not match eventual testing
      conditions.

PMID- 16615395
TI  - Mixing costs in task shifting reflect sequential processing stages in a
      multicomponent task.
AB  - We investigated the hypothesis that mixing costs intask shifting reflect th e
      sequential selection of task components (e.g., stimulus categories) during task
      execution. This proposition was supported by Hubner, Futterer, and Steinhauser
      (2001), who showed that the amount of mixing costsdepends on the number of mixed
      task components (e.g., stimulus level and judgment). However, their results could
      also be explained by a task set selection account, because task components and
      task sets were confounded. In Experiments 1 and 2, we compared conditions in
      which either the number of task sets varied and the number of mixed task
      components was constant or vice versa. Only the number of mixed task components
      was predictive for the mixing costs. In Experiment 3, we replicated the
      additivity of mixing costs from level a ndjudgment mixing. Our results suggest
      thatthe mixingcosts reflect a selection strategy in which interference is reduced
      in a stepwise manner.

PMID- 16615394
TI  - The role of response selection and input monitoring in solving simple
      arithmetical products.
AB  - Several studies have already shown that the central executive, as conceptualized
      in the working memory model of Baddeley and Hitch (1974), is important in simple
      mental arithmetic. Recently, attempts have been made to define more basic
      processes that underlie the "central executive." In this vein, monitoring,
      response selection, updating, mental shifting, and inhibition have been proposed
      as processes capturing executive control. Previous research has shown that
      secondary tasks that require a choice decision impair the calculation of simple
      sums, whereas input monitoring has not been found to be a sufficient condition to
      impair the calculation of sums (Deschuyteneer & Vandierendonck, 2005). In the
      present article, we report data on the role of input monitoring and response
      selection in solving simple arithmetical products. In four experiments,
      participants solved one-digit products (e.g., 5 x 7) in a single-task, as well as
      in a dual-task, condition. Just as for solving simple sums, the results show a
      strong involvement of response selection in the calculating of simple products,
      whereas input monitoring does not seem to impair the calculation of such
      products. These findings give additional evidence that response selection may be
      one of the processes needed for solving simple mental arithmetic problems.

PMID- 16615396
TI  - Who's sorry now?

PMID- 16615397
TI  - Apologies and a strong defense at the University of Michigan Health System.

PMID- 16615398
TI  - Full disclosure and apology--an idea whose time has come.

PMID- 16615399
TI  - Lawyers say 'sorry' may sink you in court.

PMID- 16615400
TI  - Long-term solution to malpractice crises: reduce harm to patients.
AB  - Physician executives need to lead the charge and actually reduce harm to
      patients. Simply capping malpractice awards or changing the rules of litigation
      is not enough.

PMID- 16615401
TI  - Conversations at the top of the world: ACPE delegation travels to China and
      Tibet.

PMID- 16615402
TI  - Unexplained clinical variance: are health plans (partly) responsible?
AB  - More research is needed to determine if health plan decision making is
      contributing to clinical variance in health care. But an informal survey shows it
      is.

PMID- 16615403
TI  - Senior physician slowdown-problem or opportunity?
AB  - Examine a plan for physician slowdown or relief of call and learn how it can
      extend the professional lives of experienced physicians at a time when practices
      are facing a physician shortage.

PMID- 16615404
TI  - Climbing the ladder to CEO part II: leadership and business acumen.

PMID- 16615405
TI  - The 12-step innovation roadmap: how to analyze and prioritize new business ideas.

PMID- 16615406
TI  - Do you know your "innovation fulcrum"?

PMID- 16615407
TI  - Look what's happened to medical ethics: broader horizons, updated ideas, fresh
      language.

PMID- 16615408
TI  - Gain sharing revisited.

PMID- 16615409
TI  - Building the relationships required to influence others.

PMID- 16615410
TI  - An investigation of the housing environment for persons with asthma and persons
      without asthma.
AB  - Asthma is a chronic disease affected by environmental factors that may increase
      symptoms that impact on a persons' well-being. An important issue in occupational
      therapy is to improve the relationship between a person's functional capacity and
      the physical environment. The aim of the study was to compare the housing
      environment of persons with asthma (cases, n = 49) and persons without asthma
      (controls, n = 48), with regard to building construction and condition, physical,
      chemical and biological factors, and cleaning routines. A secondary aim was to
      compare different types of accommodation within cases and controls. A specialist
      team, including a construction engineer, a biological scientist, and an
      occupational therapist, conducted the study. Data were collected using protocols,
      as well as a number of established technical methods from the field of
      occupational and environmental medicine. The primary results showed no major
      differences in the housing environment between the two groups. However, in
      individual homes environmental factors at levels that could increase symptoms
      were identified. When single-family houses were compared with multi-family
      houses, significant differences were found indicating that preventive
      interventions may be needed in some single-family houses. Further studies are
      needed to clarify the person-environment relationship for persons with asthma,
      focusing on their ability to perform daily activities.

PMID- 16615411
TI  - Effects of constraint-induced movement therapy in adolescents with hemiplegic
      cerebral palsy: a day camp model.
AB  - This study examined whether restraining the dominant hand during an intensive
      training period could provide a means by which to improve adolescents' hemiplegic
      hand function. Nine adolescents with hemiplegic CP between the ages of 13 and 18
      years were enrolled at a two-week day camp, of 7 hours/day. They were restricted
      in the use of their dominant hand in various daily and recreational activities by
      wearing a glove-like splint. The basis for intervention was built upon the
      adolescents' own motivation, and the activities were chosen to be challenging and
      specifically to provide opportunities for repetition. The treatment approach used
      was an adapted model of Constraint Induced Movement Therapy. Assessments took
      place before and after intervention as well as at a 5-month follow-up. The
      results revealed that hand function did improve and was sustained at follow-up
      for dexterity, coordination and precision, and manipulative abilities. The
      performance of tasks that had been trained specifically showed major
      improvements.

PMID- 16615412
TI  - Psychometric properties of the Satisfaction with Daily Occupations (SDO)
      instrument and the Manchester Short Assessment of Quality of Life (MANSA) in
      women with scleroderma and without known illness.
AB  - This study investigated whether two instruments devised for people with mental
      illness, the Satisfaction with Daily Occupations (SDO) instrument and the
      Manchester Short Assessment of Quality of Life (MANSA), showed appropriate
      psychometric properties in terms of internal consistency, convergent/divergent
      validity, and discriminant validity when used with other samples. The study group
      comprised two female samples, one with physical disability (scleroderma) and one
      reference sample without known illness. It was hypothesized that the associations
      from SDO would be low or moderate to both general life satisfaction and self
      rated health. The results confirmed that the associations were equal in size in
      both samples, but still the relationship to general life satisfaction in the
      scleroderma sample was somewhat higher than expected. Regarding the MANSA quality
      of life, the hypotheses were that the quality of life-index would show high
      correlations with general life satisfaction and moderate with self-rated health,
      and these hypotheses were confirmed for the reference sample, indicating that
      quality of life as measured by the MANSA converged with general life satisfaction
      but mainly diverged from self-rated health. In the scleroderma sample, the
      association to health was higher than expected. Both instruments appeared to
      reflect constructs that were stable across the two investigated groups, and both
      measures could distinguish the disability group from the healthy group. The SDO
      obtained a good value on internal consistency in the sample with scleroderma but
      a somewhat low value in the reference group, while the quality of life aspect of
      the MANSA exhibited good internal consistency in both samples. The instruments
      showed promising properties, indicating that they could be used for the target
      groups. However, both measures need further testing of psychometric properties.

PMID- 16615413
TI  - Evaluating leisure activities in the oldest old.
AB  - AIM: To determine whether the Modified NPS Interest Checklist (MNPS) could be
      developed as a tool with linear measures of four dimensions of leisure: Interest,
      Performance, Motivation, and Well-being. METHODS: A cross-sectional descriptive
      study including 156 volunteers born between 1904 and 1917 and living in urban or
      rural northern Sweden. Each participant was individually interviewed at her/his
      place of residence. Subsequent data were subjected to a series of Rasch analyses
      using FACETS. MAJOR FINDINGS: The items and persons demonstrated acceptable
      goodness-of-fit across all four dimensions in the MNPS checklist. The Rasch
      equivalent of Cronbach's alpha was 0.98 for items, and ranged from 0.66 to 0.75
      for persons. PRINCIPAL CONCLUSION: The MNPS shows evidence for acceptable
      internal scale validity, person response validity, and scale reliability. This
      study provides initial evidence that the MNPS is a valid tool for measuring
      leisure among the oldest old. While this study provides the first psychometric
      examination of an assessment designed to evaluate different dimensions of
      leisure, more research is needed to further assess validity and reliability of
      this tool with the elderly and with other groups.

PMID- 16615414
TI  - Criterion validity of the Occupational Therapy Adult Perceptual Screening Test
      (OT-APST).
AB  - This paper reports on the criterion validity of the Occupational Therapy Adult
      Perceptual Screening Test (OT-APST) including concurrent criterion validity and
      its sensitivity and specificity. The performance of 208 people following stroke
      on the OT-APST and a reference tool (either the Loewenstein Occupational Therapy
      Cognitive Assessment (LOTCA) or the LOTCA--Geriatric version (LOTCA-G)) was
      compared. The OT-APST subscale scores and performance outcome (intact or
      impaired) on related subscales of the reference tool was analyzed to evaluate the
      concurrent criterion validity of the OT-APST and its sensitivity and specificity
      at selected cut-off scores. Significant correlations were found between
      participants' performance (intact or impaired) on the reference tool and scores
      on the OT-APST. The sensitivity and specificity of the OT-APST were analyzed at
      selected cut-off scores to explore the validity of decisions based on OT-APST
      performance when compared with the reference tool. This study shows that the OT
      APST is a tool with demonstrated concurrent criterion validity for the assessment
      of visual perception.

PMID- 16615415
TI  - Construct and ecological validity of the Occupational Therapy Adult Perceptual
      Screening Test (OT-APST).
AB  - This paper reports on the construct validity (scale design and convergent
      validity) and ecological validity of the Occupational Therapy Adult Perceptual
      Screening Test (OT-APST). The performance of 208 participants following stroke on
      the OT-APST and a reference tool (either the Loewenstein Occupational Therapy
      Cognitive Assessment (LOTCA) or the LOTCA-Geriatric version (LOTCA-G)) was
      compared. The OT-APST performance of the stroke sample was compared with a
      healthy normative sample (n = 356). The relationship between the OT-APST
      performance and the Functional Independence Measure (FIM) score of the
      participants following stroke was also examined. Factor analysis and internal
      consistency results supported the scale design of the OT-APST. Significant
      correlations between the performance of the participants following stroke on the
      OT-APST and the reference tool supported the convergent validity of the OT-APST.
      The ability of the OT-APST to separate the two participant groups provided
      further evidence of its construct validity. Significant correlations between OT
      APST and FIM scores supported the ecological validity of this tool. This study
      shows that the OT-APST is an ecologically valid tool with demonstrated construct
      validity in the assessment of visual perception.

PMID- 16615416
TI  - Evaluation of vascularized graft reconstruction of the mandible with Tc-99m MDP
      bone scintigraphy.
AB  - AIM: The aim of this study was to evaluate the value of bone scintigraphy for the
      assessment of graft viability following vascularized bone grafts in patients with
      mandibular reconstruction. METHODS: We investigated 16 patients with vascularized
      grafts from the fibula (13 patients) and iliac crest (3 patients) in the last 8
      years. For the follow up of all these patients, Tc-99m MDP bone scintigraphy was
      performed between 2-10 days postoperatively. SPECT study was included in 5
      patients. For the evaluation of the grafts, a six-grade scoring system was used.
      The grading system was based on a comparison of tracer uptake between graft and
      the cranium. The uptake was defined as increasing from grade 6 to grade 1.
      RESULTS: Thirteen of the 16 grafts had an uncomplicated clinical course.
      Complications in the graft occurred in three patients. In the analysis of planar
      scintigrams, patients with uncomplicated healing showed increased uptake in 12 of
      the 13 grafts (grade 1-3) and 1 showed the same level tracer uptake compared to
      cranium (grade 4). In the failed 3 grafts, decreased uptake was observed (grade 5
      and 6). In 5 patients, SPECT was performed in addition to planar imaging. In
      these patients, 4 of the 5 grafts had an uncomplicated clinical course and 1 had
      a complicated one. In the analysis of SPECT images, while all the grafts with an
      uncomplicated clinical course exhibited increased uptake (grade 1-3), the failed
      graft showed decreased uptake (grade 6). CONCLUSION: Three-phase bone
      scintigraphy performed within 10 days after the mandibular reconstruction is a
      useful tool to monitor the viability and early complications of vascularized
      mandibular bone grafts. SPECT is also recommended. It may contribute to
      interpretation of the bone scans and to precise assessment of graft viability.

PMID- 16615417
TI  - Correction factors after having neglected the first exponential in the estimation
      of chromium-51 EDTA clearance: a reappraisal.
AB  - The aim of the present work was to evaluate two classical formulae allowing the
      correction for having neglected the first exponential in the slope-intercept
      method used for the determination of EDTA clearance, namely the Chantler's linear
      correction formula (CH) and the Brochner-Mortensen's quadratic correction formula
      (BM). First, a comparison study was performed with the two correction formulae,
      in order to predict the behavior of the calculated clearance, for various levels
      of renal function. Second, using data obtained from 47 adult patients with normal
      renal function, the results obtained with the two correction formulae have been
      compared to the reference technique, namely the biexponential fit. The results of
      the comparison study indicated that for clearance values lower than 120 ml/min,
      the results obtained using CH were systematically lower than those of BM, whereas
      for clearance values between 120 and 140 ml/min, the reverse was observed. The
      differences however, never exceeded 8 ml/min. The results were quite different
      when the clearance was higher than 140 ml/min, when the difference between CH and
      BM results increased rapidly, and the BM provided values systematically lower
      than CH. The clinical study showed that, in the range of normal clearance values,
      both CH and BM clearances were slightly lower than the results obtained by means
      of the reference technique. Based on these results, a new specifically designed
      validation study involving patients with high clearance values is mandatory to
      determine which of these two correction methods is more accurate, or to devise a
      better correction formula.

PMID- 16615418
TI  - Brain perfusion abnormalities in chronic obstructive pulmonary disease:
      comparison with cognitive impairment.
AB  - OBJECTIVES: To clarify cerebral perfusion distribution and cognitive functions in
      patients with chronic obstructive pulmonary disease (COPD) according to the
      hypoxia levels and to assess if there is a relationship between cognitive
      impairment and cerebral perfusion index. PATIENTS AND METHODS: Eight patients
      with stable hypoxemic COPD (HC), 10 patients with stable nonhypoxemic COPD (NHC),
      and 10 age-matched healthy volunteers participated in the study. All subjects
      underwent a complete neuropsychological assessment with the mental deterioration
      battery (MDB), Wechsler memory scale-revised (WMS-R), color trail test (CCT), and
      grooved pegboard test (GPT). SPECT examination with Tc-99m HMPAO was performed in
      all patients and controls. Quantitative analysis was performed by a region of
      interest (ROI)-based method. RESULTS: The scores of verbal memory, delayed recall
      and attention were significantly lower in COPD patients (p < 0.01). The scores of
      other subtests were similar in patients and controls. Comparing NHC patients to
      HC groups showed that verbal memory was impaired in both groups, but delayed
      recall and attention scores were significantly worse in HC patients than NHC
      patients. Perfusion indexes on frontal ROIs in NHC patients and frontal and
      parietal ROIs in HC patients showed significant decreases. Our scintigraphic
      findings were correlated with the results of neuropsychological tests.
      CONCLUSIONS: Our results demonstrate that cerebral perfusion is significantly
      altered in COPD patients. Hypoxemic patients showed more deterioration in
      cerebral perfusion and cognitive performance than nonhypoxemic patients. The
      relationship between decreased perfusion and cognitive impairment and the
      clinical significance of these results require further studies in larger
      populations.

PMID- 16615420
TI  - Fluorine-18-fluorodeoxyglucose positron emission tomography for assessment of
      patients with unresectable recurrent or metastatic lung cancers after CT-guided
      radiofrequency ablation: preliminary results.
AB  - OBJECTIVES: We compared the diagnostic value of fluorine-18-fluorodeoxyglucose
      positron emission tomography (FDG-PET) with that of computed tomography (CT)
      following radiofrequency ablation (RFA) of inoperable recurrent or metastatic
      cancers in the lung. METHODS: Twelve patients (9 males and 3 females; 5 had
      recurrent lung cancer and the other 7 had metastatic nodules from a variety of
      primary cancers) were treated by RFA for 17 pulmonary nodules. FDG-PET was
      performed before and 2 months after RFA, and the mean standardized uptake value
      (SUV) was calculated. The response evaluation was based on the percent reduction
      relative to the baseline and the absolute values of SUV on FDG-PET performed at 2
      months after RFA. We compared the response evaluations made based on findings of
      FDG-PET and CT at 2 and > or =6 months (mean 10.2) after RFA. RESULTS: The
      percent reduction in uptake at 2 months was significantly lower in nodules
      considered progressive (69.6 +/- 18.6%) than nonprogressive disease (38.7 +/-
      12.5%; p < 0.01) based on CT findings at > or =6 months after RFA. The absolute
      SUV at 2 months was significantly higher in nodules considered progressive (2.61
      +/- 0.75) than nonprogressive disease (1.05 +/- 0.67; p < 0.01) based on CT
      findings at > or =6 months post-RFA. CONCLUSION: Although our pilot study
      comprised few cases of various histopathological types of cancers in the lung,
      the results suggest that FDG-PET could predict regrowth on subsequent follow-up
      CT. Regrowth could be diagnosed earlier by FDG-PET than by CT, and nodules with
      residual uptake and with <60% reduction of uptake relative to baseline on FDG-PET
      at 2 months after ablation might require additional therapy.

PMID- 16615419
TI  - Comparison of 201Tl-chloride SPECT with 99mtc-MIBI SPECT in the depiction of
      malignant head and neck tumors.
AB  - OBJECTIVE: Comparison of 201Tl chloride SPECT (TI-SPECT) with 99mTc-MIBI SPECT
      (MIBI-SPECT) in the depiction of malignant head and neck tumors was prospectively
      studied. METHODS: Forty-one patients with various tumors of the head and neck
      were included in this prospective study. Histologically, 36 patients had squamous
      cell carcinomas, 3 undifferentiated carcinomas, 1 transitional cell carcinoma,
      and 1 MALT lymphoma. All patients underwent a simultaneous dual-isotope SPECT of
      the head and neck with 201Tl and 99mTc-MIBI. Dual-isotope SPECT for early (n=41)
      and delayed acquisition (n=21) was performed. Qualitatively, 3 observers
      evaluated both TI-SPECT and MIBI-SPECT individually. The interpretation criteria
      were graded as grade 1 (no abnormal increased uptake) to 5 (definitely increased
      uptake of a degree equal to or greater than that of normal salivary gland).
      Statistical analysis of the comparison of Tl-SPECT and MIBI-SPECT was performed.
      The interobserver difference was evaluated using the kappa-coefficient.
      Quantitatively, T/N ratio (the ratio of the counts in the tumor divided by that
      in the normal nuchal muscles) and retention index were compared between TI-SPECT
      and MIBI-SPECT. RESULTS: On both the early and delayed images, the grades of
      uptake of the tumor in TI-SPECT were significantly higher than those in MIBI
      SPECT by three observers. The grade of Tl-uptake of the tumor on the delayed
      images was 5 for all observers (kappa-coefficient=1); however, the kappa
      coefficient varied from 0.39 to 0.84 in early T1-SPECT, and in early and delayed
      MIBI-SPECT. Statistical differences in T/N ratio were noted between early TI
      SPECT (2.87 +/- 1.19) and MIBI-SPECT (2.48 +/- 1.06), and between delayed Tl
      SPECT (2.11 +/- 0.70) and MIBI-SPECT (1.20 +/- 0.48). The retention index or Tl
      SPECT (0.81 +/- 0.24) was significantly higher than that of MIBI-SPECT (0.52 +/-
      0.15). CONCLUSIONS: The present study qualitatively and quantitatively showed
      that 201Tl had higher accumulation in the tumor than 99mTc-MIBI in both early and
      delayed images.

PMID- 16615421
TI  - Usefulness of FDG-microPET for early evaluation of therapeutic effects on VX2
      rabbit carcinoma.
AB  - PURPOSE: The aim of this study was to determine the potential use of high
      resolution FDG-microPET for predicting the primary effects of radiotherapy and/or
      hyperthermia on tumor-bearing rabbits. METHODS: Twenty-eight VX2 xenografts in
      the thighs of rabbits were divided into the following 5 treatment groups:
      radiotherapy at a single dose of 10, 20 or 30 Gy, hyperthermia (43 degrees
      Celsius, 1 hour), and the combination of radiotherapy and hyperthermia (10 Gy +
      43 degrees Celsius, 1 hour). FDG-microPET images were obtained by using a
      microPET P4 system at pretreatment and at 24 hours and 7 days after treatment.
      For the evaluation by FDG-microPET, tumor/muscle (T/M) ratios, retention index
      [RI = (T/M ratio at 120 min - T/M ratio at 60 min) / T/M ratio at 60 min], and
      time activity curve (TAC) were acquired. RESULTS: We divided the xenografts into
      a responder group (partial response + stable disease, n=14) and a non-responder
      group (progressive disease, n = 14). The T/M ratio at 24 hours after the
      treatment in the responder group was decreased remarkably with that at pre
      treatment (p < 0.05), while in the non-responder group it showed no significant
      change between the time points. The RI and TAC patterns were comparable to T/M
      ratios in each treatment group. T/M ratios, RI, and TAC indicated marked changes
      at the time point of 24 hours in the responder group, although the tumors did not
      show any significant hange in volume at that time. Photomicrographs of sections
      showed that the number of viable tumor cells in the responder group decreased at
      24 hours after treatment and that inflammatory cell infiltration was marked and
      almost all viable tumor cells had disappeared by day 7 after treatment.
      CONCLUSION: These results suggest that early evaluation by FDG-microPET,
      especially 24 hours after treatment, is useful to predict the primary effects of
      the treatment. Histological analysis showed that inflammatory cell infiltration
      at 7 days after treatment was considered to be a cause of accumulation of FDG in
      the tumors that showed a significant decrease in tumor cell number. This false
      positive should be noted when predicting tumor response by FDG accumulation.

PMID- 16615422
TI  - Database of normal human cerebral blood flow measured by SPECT: I. Comparison
      between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled
      water PET and voxel-based morphometry.
AB  - OBJECTIVES: Three accumulative tracers, iodine-123-labeled N-isopropyl-p
      iodoamphetamine (I-123-IMP), technetium-99m-labeled hexamethylpropyleneamineoxime
      (Tc-99m-HMPAO), and technetium-99m-labeled ethyl cysteinate dimer (Tc-99m-ECD)
      are widely used to measure cerebral blood flow (CBF) in single-photon emission
      computed tomography (SPECT). In the present study, normal regional distribution
      of CBF measured with three different SPECT tracers was entered into a database
      and compared with regional distribution of CBF measured by positron emission
      tomography (PET) with H2(15)O. The regional distribution of tissue fractions of
      gray matter determined by voxel-based morphometry was also compared with SPECT
      and PET CBF distributions. METHODS: SPECT studies with I-123-IMP, Tc-99m-HMPAO,
      and Tc-99m-ECD were performed on 11, 20, and 17 healthy subjects, respectively.
      PET studies were performed on 11 healthy subjects. Magnetic resonance (MR)
      imaging studies for voxel-based morphometry were performed on 43 of the 48
      subjects who underwent SPECT study. All SPECT, PET, and MR images were
      transformed into the standard brain format with the SPM2 system. The voxel values
      of each SPECT and PET image were globally normalized to 50 ml/100 ml/min. Gray
      matter, white matter, and cerebrospinal fluid images were segmented and extracted
      from all transformed MR images by applying voxel-based morphometry methods with
      the SPM2 system. RESULTS: Regional distribution of all three SPECT tracers
      differed from that of H2150 in the pons, midbrain, thalamus, putamen,
      parahippocampal gyrus, posterior cingulate gyrus, temporal cortex, and occipital
      cortex. No significant correlations were observed between the tissue fraction of
      gray matter and CBF with any tracer. CONCLUSION: Differences in regional
      distribution of SPECT tracers were considered to be caused mainly by differences
      in the mechanism of retention of tracers in the brain. Regional distribution of
      CBF was independent of regional distribution of gray matter fractions, and
      consequently the blood flow per gray matter volume differed for each brain
      region.

PMID- 16615423
TI  - Database of normal human cerebral blood flow measured by SPECT: II.
      Quantification of I-123-IMP studies with ARG method and effects of partial volume
      correction.
AB  - The limited spatial resolution of SPECT causes a partial volume effect (PVE) and
      can lead to the significant underestimation of regional tracer concentration in
      the small structures surrounded by a low tracer concentration, such as the
      cortical gray matter of an atrophied brain. The aim of the present study was to
      determine, using 123I-IMP and SPECT, normal CBF of elderly subjects with and
      without PVE correction (PVC), and to determine regional differences in the effect
      of PVC and their association with the regional tissue fraction of the brain.
      METHODS: Quantitative CBF SPECT using 123I-IMP was performed in 33 healthy
      elderly subjects (18 males, 15 females, 54-74 years old) using the
      autoradiographic method. We corrected CBF for PVE using segmented MR images, and
      analyzed quantitative CBF and regional differences in the effect of PVC using
      tissue fractions of gray matter (GM) and white matter (WM) in regions of interest
      (ROIs) placed on the cortical and subcortical GM regions and deep WM regions.
      RESULTS: The mean CBF in GM-ROIs were 31.7 +/- 6.6 and 41.0 +/- 8.1 ml/100 g/min
      for males and females, and in WM-ROIs, 18.2 +/- 0.7 and 22.9 +/- 0.8 ml/100 g/min
      for males and females, respectively. The mean CBF in GM-ROIs after PVC were 50.9
      +/- 12.8 and 65.8 +/- 16.1 ml/100 g/min for males and females, respectively.
      There were statistically significant differences in the effect of PVC among ROIs,
      but not between genders. The effect of PVC was small in the cerebellum and
      parahippocampal gyrus, and it was large in the superior frontal gyrus, superior
      parietal lobule and precentral gyrus. CONCLUSION: Quantitative CBF in GM
      recovered significantly, but did not reach values as high as those obtained by
      invasive methods or in the H2(15)O PET study that used PVC. There were
      significant regional differences in the effect of PVC, which were considered to
      result from regional differences in GM tissue fraction, which is more reduced in
      the frontoparietal regions in the atrophied brain of the elderly.

PMID- 16615424
TI  - Cutaneous metastatic lung cancer detected with 18F-FDG PET.
AB  - A 48-year-old male smoker presented with a chief complaint of persistent cough
      for three months. A CT scan revealed only a large right paratracheal mass. The
      plan was to obtain histological confirmation of suspected lung cancer via
      bronchoscopy and mediastinoscopy. A whole body 18F-FDG (2-deoxy-2-[18F]fluoro-D
      glucose) PET Scan was ordered for staging and localization of the most accessible
      biopsy site. There was a large, intense hypermetabolic focus corresponding to the
      paratracheal lesion seen on CT, as well as a lesion in the right adrenal gland.
      There was also a superficial, subcutaneous hypermetabolic lesion in the mid-back.
      The subcutaneous lesion, which previously had not been noted, was biopsied and
      proved to be metastatic adenocarcinoma consistent with the lung primary. This
      case illustrates the clinical utility of reporting soft tissue abnormalities,
      which may provide an alternative, more readily accessible location for biopsy
      that is both safer and less expensive than bronchoscopy or mediastinoscopy.

PMID- 16615425
TI  - Diagnosis of aseptic deep venous thrombosis of the upper extremity in a cancer
      patient using fluorine-18 fluorodeoxyglucose positron emission
      tomography/computerized tomography (FDG PET/CT).
AB  - We describe a patient with a history of recurrent squamous cell carcinoma of the
      tongue and abnormal FDG uptake in the left arm during a re-staging FDG PET/CT.
      After revision of the patient's clinical history, tests and physical exam, the
      abnormal FDG uptake was found to correspond to an extensive aseptic deep venous
      thrombosis of the upper extremity.

PMID- 16615426
TI  - A case of non-hodgkin's lymphoma of the ovary: usefulness of 18F-FDG PET for
      staging and assessment of the therapeutic response.
AB  - Primary ovarian lymphoma as the initial manifestation is rare. A 27-year-old
      woman presented to our hospital with the symptoms of lower abdominal fullness and
      pollakisuria. CT scan and MRI revealed bilateral ovarian tumors, which showed
      heterogeneous masses. 18F-FDG PET revealed strong uptake by the abdominal masses,
      and the maximum standardized uptake value (SUVmax) was 12.5. Abnormal uptake was
      not shown by other regions. An exploratory laparotomy was performed. Histological
      findings revealed diffuse large B-cell lymphoma. The clinical stage was IV
      according to the Ann Arbor system. International prognostic index (IPI) was 3
      (high-intermediate risk). Chemotherapy was administered consisting of three
      courses of an R-CHOP regimen, and 18F-FDG PET and CT scan revealed no signs of
      involvement 3 months after initiation of the chemotherapy. 18F-FDG PET was a
      useful method for staging and assessment of the therapeutic response in primary
      ovarian lymphoma.

PMID- 16615427
TI  - Positive gallium-67 and thallium-201 scans in thymic rebound after chemotherapy
      for lymphoma.
AB  - It is a diagnostic problem to distinguish thymic rebound or rebound thymic
      hyperplasia from thymic malignancy, but it is frequently made more difficult
      because most patients have had previous malignancies. Recently we evaluated a six
      year-old girl with thymic rebound after chemotherapy for lymphoma, by both
      gallium-67 and thallium-201 scans. On gallium-67 scan, intensive uptake was seen
      in the anterior mediastinum. CT revealed a triangular-shaped, homogeneous mass in
      the anterior mediastinum. On early scan of thallium-201 study, slight
      accumulation was seen in the anterior mediastinum and was enhanced in delayed
      scans. Considering the clinical state and imaging results, thymic rebound after
      chemotherapy was the most likely diagnosis, and follow-up observation was done
      without therapy. During the course, there were no signs of relapse. Some reports
      have described both positive and negative thallium-201 accumulation in thymic
      rebound. Although more experience with similar cases is necessary, it is likely
      that thallium-201 also tends to accumulate in thymic rebound as well as gallium
      67.

PMID- 16615428
TI  - [Magnetic resonance imaging of olfactory neuroblastoma].
AB  - Olfactory neuroblastoma is an uncommon intranasal tumor originating from
      olfactory neuroepithelium. Despite the development of electron microscopy and
      immunohistochemical testing, the pathological diagnosis of this tumor is still
      difficult because of the wide range of histological features. Magnetic resonance
      imaging (MR) of this tumor and the pattern of contrast enhancement have not been
      well described. The purpose of this report was to analyze the MR characteristics
      of olfactory neuroblastomas. The MR signal, pattern of contrast enhancement, and
      correlation with high-resolution computed tomography (CT) imaging were examined.
      Seventeen patients with olfactory neuroblastoma were treated at Hokkaido
      University Hospital and a related hospital during the past 25 years. MR images
      taken in 12 patients and CT images taken in 9 patients with histologically
      confirmed olfactory neuroblastoma were retrospectively reviewed. Compared with
      brain gray matter, 11 tumors were hypointense on T1-weighted images, 9
      homogeneously and 2 heterogenously. Eight tumors were hyperintense on T2-weighted
      images, 3 homogeneously and 5 heterogeneously, although their appearance was less
      intense than that of sinusitis. Gadolinium enhancement was moderate in one case
      and marked in 10 of the 11 cases, 9 homogeneously and 2 heterogeneously. Nine of
      the 11 tumors showed smooth regular shaped margins; 2 of these tumors exhibited
      irregular infiltrating margins on gadolinium-enhanced images, compared to the pre
      contrast T1-weighted images. Eight of the 11 tumors had clearly demarcated
      margins, while 3 of the 11 tumors did not exhibit gadolinium enhancement. Six of
      the 12 cases (50%) exhibited intracranial cysts on the gadolinium-enhanced
      images. T2-weighted or gadolinium-enhanced images successfully distinguished
      sinusitis from tumors in 4 cases whereas the CT images failed. Gadolinium
      enhancement, particularly in the tangential plane, demonstrated intracranial
      extension not apparent on the CT images in one case. In most cases, olfactory
      neuroblastomas are hypointense on T1-weighted images, hyperintense on T2-weighted
      images, and show marked homogeneous enhancement with well-demarcated regular
      margins upon gadolinium enhancement. Although the definite diagnosis is based on
      histopathology findings and MR features are nonspecific, they may suggest an
      imaging diagnosis of olfactory neuroblastoma when seen in the superior nasal
      cavity. MR is superior to CT both in delineating the extent of the tumor and in
      making an imaging diagnosis.

PMID- 16615429
TI  - [Adjuvant chemotherapy (nedaplatin/UFT) after concurrent chemoradiotherapy for
      locally advanced head and neck squamous cell carcinoma].
AB  - To evaluate the efficacy of adjuvant chemotherapy after concurrent
      chemoradiotherapy, 41 previously untreated patients with locally advanced and
      resectable head and neck squamous cancer were enrolled in a study to compare
      adjuvant chemotherapy (Nedaplatin/UFT) after concurrent chemoradiotherapy (CDDP/5
      FU) and concurrent chemoradiation alone. Nine of the patients had stage III
      tumors and 32 had stage IV tumors. The primary tumor site was the hypopharynx in
      14 patients, the larynx in 12 patients, the oral cavity in 9 patients, and the
      oropharynx in 6 patients. Treatment consisted of 6 courses of Nedaplatin (80
      mg/m2) repeated at 4-week intervals and one year of the oral administration of
      UFTE (400 mg/day) after concurrent chemoradiotherapy at an outpatient clinic.
      Toxicities included leukopenia (grade 3, 15.4%) and thrombocytopenia (grade 3,
      7.7%). One death from a gastric ulcer occurred. The median overall survival time
      was 30.1 months (5.5-50.1 months) for the adjuvant chemotherapy group and 21.7
      months (4.0-48.8 months) for the control group. The progression-free survival
      period was 22.8 months (5.6-33.9 months) for the adjuvant chemotherapy group and
      26.5 months (5.6-33.9 months) for the control group. The two-year overall
      survival rate was 73.3% for the adjuvant chemotherapy group and 55.7% for the
      control group. A significant difference was observed in the two-year progression
      free survival rates: 66.9% for the adjuvant chemotherapy group and 27.8% for the
      control group (p = 0.03290). Among the patients with a partial response to
      concurrent chemoradiotherapy, in particular, a significant difference in the two
      year progression-free survival rates was seen : 59.3% for the adjuvant
      chemotherapy group and 15.3% for the control group (p = 0.01102). The rate of
      loco-regional failure was 29.6% for the adjuvant chemotherapy group and 64.3% for
      the control group (p = 0.0716). Distant metastasis was not detected in either
      group. The rate of organ preservation was 66.7% for the adjuvant chemotherapy
      group and 35.7% for the control group (p = 0.1183). This adjuvant chemotherapy
      regimen might improve the loco-regional control rates after concurrent
      chemoradiotherapy.

PMID- 16615430
TI  - [Fluticasone propionate aqueous nasal spray for the treatment of chronic
      sinusitis with eosinophil].
AB  - Chronic sinusitis with eosinophils easily recurs after endoscopic sinus surgery.
      The condition is usually complicated by asthma, and many eosinophils are present
      in the sinus mucosa. One conservative treatment method is the administration of
      glucocorticoids locally or systematically. To evaluate the efficacy and
      tolerability of intranasal fluticasone propionate for the treatment of chronic
      sinusitis with eosinophils, seven patients with chronic sinusitis with
      eosinophils were treated over a 12-week period using a fluticasone propionate
      aqueous nasal spray (800 microg per day in each nostrilz). The Symptons of 7
      patients, especially nasal discharge and nasal obstructions, improved and an
      expanded air space was observed on paranasal CT images. The percent of drug
      systemically available after intranasal administration varied by less than 1% for
      intranasal fluticasone propionate. Therefore, even if intranasal fluticasone
      propionate is administerved at double the usual dose, it is unlikely to cause
      systemic side effects. Fluticasone propionate aqueous nasal spray at double the
      usual dose is effective for the treatment of chronic sinusitis with eosinophils.

PMID- 16615431
TI  - [Implication of vascular endothelial growth factor (VEGF) in human head and neck
      cancer].
AB  - PURPOSE: Metastatic activity is one parameter indicating the malignancy of tumor
      cells. Angiogenesis has now been extensively studied to clarify the mechanisms of
      tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is an
      angiogenic cytokine expressed by many human and animal tumors. We studied the
      role of VEGF in tumor growth by transfecting the VEGF gene into tumor cells and
      analyzing the survival period of nude mice implanted with these transfected tumor
      cells. MATERIALS AND METHODS: Cell line: The tumor cell line, OKK-LN, was
      established from human maxillary squamous cell carcinoma and used in this study.
      The tumor cells did not produce VEGF in the culture supernatant. Transfection:
      OKK-LN cells were stably transfected with sense VEGF165 cDNA or with the vector
      alone. The full-length VEGF165 cDNA was cloned into an expression vector
      (pCIneo). The DNA transfection was performed by the lipofection method, and the
      limiting dilution method was used for cloning. ELISA was used to measure VEGF in
      the culture supernatant. As a control, OKK-LN cells were transfected with the
      vector alone without VEGF (OKK-LN/pCIneo). The tumor cells were subcutaneously
      injected into nude mice (Balb/c nu/nu, 6W), and the survival period and tumor
      volume were analyzed. Effects of angio-suppressive agent, TNP-470, and anti-VEGF
      antibody on tumor growth and angiogenesis: TNP-470 (supplied by Takeda
      Pharmaceutical Co., Ltd.) and monoclonal anti-human VEGF antibodies were
      intraperitoneally administered to mice implanted with tumor cells once a week and
      twice a week for 5 weeks, respectively. The effects of TNP-470 and anti-VEGF
      antibodies were analyzed by examining tumor size and survival rate and
      immunohistologically using CD31 monoclonal antibody. RESULTS: Tumor cells
      transfected with sense VEGF 165 cDNA (referred to as OKK-LN/pCIneo VEGF )
      produced VEGF in the supernatant permanently, confirming the establishment of a
      VEGF-producing human cancer cell line. We observed marked tumor growth and a
      shortened survival period by nine days in the OKK-LN/pCIneo-VEGF group, compared
      to the control group. The administration of TNP-470 and anti-VEGF antibody
      significantly suppressed tumor growth. The immunohistological study showed the
      significant suppression of a number of tumor vessels in anti-VEGF antibody
      administered mice. CONCLUSION: Our data strongly suggests that VEGF plays an
      important role in tumor growth and that treatment by anti-VEGF antibody may be a
      promising strategy against head and neck cancers.

PMID- 16615432
TI  - [History of herpesvirus research].

PMID- 16615433
TI  - [Classification of herpesviruses].

PMID- 16615434
TI  - [Molecular evolution of herpesviruses].

PMID- 16615435
TI  - [Tissue tropism of herpesviruses].

PMID- 16615436
TI  - [Distribution of herpesviruses in nature].

PMID- 16615437
TI  - [Infection and mechanism of proliferation in herpes virus].

PMID- 16615438
TI  - [Pathology of herpesvirus infection].

PMID- 16615439
TI  - [Diagnosis of herpesvirus infection].

PMID- 16615440
TI  - [Antiherpetic drugs].

PMID- 16615441
TI  - [Herpes virus infections in childhood].

PMID- 16615442
TI  - [Herpes virus infection in otolaryngology].

PMID- 16615443
TI  - [Herpesvirus infections in hematological diseases].

PMID- 16615444
TI  - [Male genital herpes].

PMID- 16615445
TI  - [Herpes virus infection in obstetrics and gynecology].

PMID- 16615446
TI  - [Herpesvirus infection in the field of ophthalmology].

PMID- 16615447
TI  - [Herpesvirus infection--oral and maxillofacial surgery].

PMID- 16615448
TI  - [Herpesvirus infections in dermatology].

PMID- 16615449
TI  - [Herpes virus infection in immunosuppressed patients].

PMID- 16615450
TI  - [Herpesviral infection in domestic and wild animals].

PMID- 16615451
TI  - [Fish herpesvirus disease].

PMID- 16615452
TI  - [Morphology of human alpha-herpesviruses].

PMID- 16615453
TI  - [HSV genes and their function].

PMID- 16615454
TI  - [Varicella-zoster virus genome and the genes].

PMID- 16615455
TI  - [Replication strategy of herpes simplex viruses].

PMID- 16615456
TI  - [Maturation and axonal transport mechanisms of alphaherpesviruses].

PMID- 16615457
TI  - [Herpes virus as a neuronal tracer].

PMID- 16615458
TI  - [Ubiquitin-proteasome pathway in herpes simplex virus infection].

PMID- 16615459
TI  - [Infection with members of the subfamily alphaherpesvirinae and intracellular
      signal transduction].

PMID- 16615460
TI  - [Molecular chaperones and herpes simplex viruses].

PMID- 16615461
TI  - [HSV infection and apoptosis].

PMID- 16615462
TI  - [Molecular mechanisms for suppression of interferon system by HSV-1 infection].

PMID- 16615463
TI  - [Immune response against HSV].

PMID- 16615464
TI  - [Immune responses to varicella-zoster virus infection].

PMID- 16615465
TI  - [Molecular mechanisms of alphaherpesviruses pathogenesis].

PMID- 16615466
TI  - [Latency and reactivation of human alphaherpesviruses].

PMID- 16615467
TI  - [HSV infection of the central nervous system].

PMID- 16615468
TI  - [Trends in antibody prevalence of herpes simplex virus types 1 and 2].

PMID- 16615469
TI  - [Molecular epidemiology of HSV infection].

PMID- 16615470
TI  - [Epidemiology of genital herpes].

PMID- 16615471
TI  - [Epidemiology of VZV infection].

PMID- 16615472
TI  - [Diagnosis of HSV-1, HSV-2 infection].

PMID- 16615473
TI  - [Diagnosis of VZV infection].

PMID- 16615474
TI  - [Serodiagnosis for alphaherpesvirinae infections].

PMID- 16615475
TI  - [Keratoconjunctivitis due to alphaherpesvirinae].

PMID- 16615476
TI  - [Acute retinal necrosis due to herpesviridae infections].

PMID- 16615477
TI  - [Genital herpes simplex virus infections].

PMID- 16615478
TI  - [Varicella].

PMID- 16615479
TI  - [Herpes zoster].

PMID- 16615480
TI  - [Herpes encephalitis].

PMID- 16615481
TI  - [Neonatal herpes].

PMID- 16615482
TI  - [Meningitis].

PMID- 16615483
TI  - [Idiopathic facial nerve paralysis (Bell's palsy)].

PMID- 16615484
TI  - [Ramsay Hunt syndrome].

PMID- 16615485
TI  - [Postherpetic neuralgia].

PMID- 16615486
TI  - [Cercopithecine herpesvirus 1 (CeHV-1)].

PMID- 16615487
TI  - [Therapy for herpes simplex virus encephalitis].

PMID- 16615488
TI  - [Treatment of neonatal herpes].

PMID- 16615489
TI  - [Treatment of alpha-herpes virus infections].

PMID- 16615490
TI  - [Treatment of alpha herpesvirus infections in ophthalmology].

PMID- 16615491
TI  - [Suppressive therapy for genital herpes simplex virus infections].

PMID- 16615492
TI  - [Varicella vaccine].

PMID- 16615493
TI  - [Development of conditionally replicating oncolytic HSV vector--targeted gene
      therapy for sarcoma by oncolytic viruses].

PMID- 16615494
TI  - [Clinical application of replication competent mutant HSV in cancer therapy].

PMID- 16615495
TI  - [Oka varicella vaccine as a novel vaccine vector].

PMID- 16615496
TI  - [New paradigm of herpes simplex virus type 1 thymidine kinase (HSV
      TK)/ganciclovir (GCV)].

PMID- 16615497
TI  - [Evaluation of animal models for cancer therapy].

PMID- 16615498
TI  - [Clinical application of replication-competent herpes simplex virus type 1
      vectors for brain tumor therapy].

PMID- 16615499
TI  - [Herpes vector-mediated gene therapy].

PMID- 16615500
TI  - [Application of herpes simplex virus to HIV vaccine vector].

PMID- 16615501
TI  - [Structure and classification of beta herpesviruses].

PMID- 16615502
TI  - [Genome structure and genetic contents of HCMV].

PMID- 16615503
TI  - [Genes and the gene products encoded by HHV-6 and HHV-7].

PMID- 16615504
TI  - [Comprehensive analysis for host and viral gene expression in cytomegalovirus
      infected cells].

PMID- 16615505
TI  - [Mechanisms of infection and replication of betaherpesviruses].

PMID- 16615506
TI  - [Immune responses in CMV infection].

PMID- 16615507
TI  - [Immune response to HHV-6 and HHV-7].

PMID- 16615508
TI  - [Mechanisms in evasion of host immune response by HCMV].

PMID- 16615509
TI  - [Pathogenicity and pathogenesis of beta-herpesviruses].

PMID- 16615510
TI  - [Latency and reactivation of HCMV].

PMID- 16615511
TI  - [Beta-herpesvirus infection of the central nervous system].

PMID- 16615512
TI  - [Mechanisms of congenital CMV infection].

PMID- 16615513
TI  - [Seroprevalence of betaherpesvirus in Japan].

PMID- 16615514
TI  - [Epidemiology of congenital cytomegalovirus infection].

PMID- 16615515
TI  - [Diagnosis of cytomegalovirus infectious diseases].

PMID- 16615516
TI  - [Diagnostic methods for HHV-6 and HHV-7 infections].

PMID- 16615517
TI  - [Exanthem subitum].

PMID- 16615518
TI  - [HHV-6 and drug-induced hypersensitivity syndrome].

PMID- 16615519
TI  - [Human cytomegalovirus in hematopoietic stem cell transplantation].

PMID- 16615520
TI  - [HHV-6 and HHV-7 infections in transplantation].

PMID- 16615521
TI  - [Chronic fatigue syndrome].

PMID- 16615522
TI  - [Congenital infection and HCMV].

PMID- 16615523
TI  - [Therapy for cytomegalovirus infection].

PMID- 16615524
TI  - [Treatment of HHV-6 and HHV-7 infections].

PMID- 16615525
TI  - [Development of drug-resistant human cytomegalovirus].

PMID- 16615526
TI  - [Development of human monoclonal antibodies to HCMV].

PMID- 16615527
TI  - [Application of human herpesvirus (HHV)-6 and HHV-7 to the gene therapy vectors].

PMID- 16615528
TI  - [Classification and structure of gamma-herpesviruses].

PMID- 16615529
TI  - [Epstein-Barr virus: genes and products].

PMID- 16615530
TI  - [KSHV genome and its gene products].

PMID- 16615531
TI  - [Mechanisms in Epstein-Barr virus infection and replication].

PMID- 16615532
TI  - [KSHV infection and its replication].

PMID- 16615533
TI  - [EBV latent gene products and the cellular signal transduction pathway].

PMID- 16615534
TI  - [Kaposi's sarcoma-associated herpesvirus and cell signaling].

PMID- 16615535
TI  - [Immune response to Epstein-Barr virus].

PMID- 16615536
TI  - [Immune modulation by KSHV].

PMID- 16615538
TI  - [Pathogenesis by gammaherpesviruses].

PMID- 16615537
TI  - [EBV and apoptosis].

PMID- 16615539
TI  - [Latent infection and reactivation of Epstein-Barr virus].

PMID- 16615540
TI  - [Mechanism of the latency and reactivation of KSHV].

PMID- 16615541
TI  - [Pathogenesis of gamma-herpesviruses-associated diseases in the context of HIV
      infection].

PMID- 16615542
TI  - [Mechanisms of EBV-mediated carcinogenesis].

PMID- 16615543
TI  - [Oncogenic mechanisms of KSHV].

PMID- 16615544
TI  - [Epidemiology of Epstein-Barr virus (EBV) infection and EBV-associated diseases].

PMID- 16615545
TI  - [Epidemiology of KSHV infection].

PMID- 16615546
TI  - [Diagnosis of EBV infection].

PMID- 16615547
TI  - [Diagnosis of KSHV infection].

PMID- 16615548
TI  - [Infectious mononucleosis].

PMID- 16615549
TI  - [Chronic active EBV infection].

PMID- 16615550
TI  - [Epstein-Barr virus (EBV)-associated lymphomas and lymphoproliferative
      disorders].

PMID- 16615551
TI  - [Posttransplant lymphoproliferative disorder].

PMID- 16615552
TI  - [EBV and nasopharyngeal carcinoma].

PMID- 16615553
TI  - [Epstein-Barr virus-associated gastric carcinoma].

PMID- 16615554
TI  - [Hypersensitivity to mosquito bites and hydroa vacciniforme].

PMID- 16615555
TI  - [Hemophagocytic syndrome associated with herpes virus infections].

PMID- 16615556
TI  - [Kaposi's sarcoma].

PMID- 16615557
TI  - [Therapeutic approach to EBV infection].

PMID- 16615558
TI  - [Cell therapy for Epstein-Barr virus-associated disease].

PMID- 16615559
TI  - [Diagnosis and treatment for EBV-associated lymphoproliferative disease].

PMID- 16615560
TI  - [Treatment of KSHV infection].

PMID- 16615561
TI  - [Development of EBV vector].

PMID- 16615562
TI  - Treatment of pediatric epilepsy: expert opinion, 2005.
AB  - BACKGROUND: Childhood epilepsies are a heterogeneous group of conditions that
      differ in diagnostic criteria and management and have dramatically different
      outcomes. Despite increasing data on treatment of epilepsy, research findings on
      childhood epilepsy are more limited and many clinical questions remain
      unanswered, so that clinicians must often rely on clinical judgment. In such
      clinical situations, expert opinion can be especially helpful. METHODS: A survey
      on pediatric epilepsy and seizures (33 questions and 645 treatment options) was
      sent to 41 U.S. physicians specializing in pediatric epilepsy, 39 (95%) of whom
      completed it. In some questions, the experts were asked to recommend overall
      treatment approaches for specific syndromes (the order in which they would use
      certain strategies). Most of the questions asked the experts to rate options
      using a modified version of the RAND 9-point scale for medical appropriateness.
      Consensus was defined as a non-random distribution of scores by chi-square test,
      with ratings used to assign a categorical rank (first line/usually appropriate,
      second line/equivocal, and third line/usually not appropriate) to each option.
      RESULTS: Valproate was treatment of choice for symptomatic myoclonic and
      generalized tonic-clonic seizures except in the very young, with lamotrigine and
      topiramate also first line (usually appropriate). Zonisamide was first line only
      if the child also has myoclonic seizures. For initial monotherapy for complex
      partial seizures, oxcarbazepine and carbamazepine were treatments of choice, with
      lamotrigine and levetiracetam also first line. As initial therapy for infantile
      spasms caused by tuberous sclerosis, viagabatrin was treatment of choice, with
      adrenocorticotropic hormone (ACTH) also first line. As initial therapy for
      infantile spasms that are symptomatic in etiology, ACTH was treatment of choice,
      with topiramate also first line. As initial therapy for Lennox-Gastaut syndrome,
      valproate was treatment of choice, with topiramate and lamotrigine also first
      line. For acute treatment of a prolonged febrile seizure or cluster of seizures,
      rectal diazepam was treatment of choice. For benign childhood epilepsy with
      centro-temporal spikes, oxcarbazepine and carbamazepine were treatments of
      choice, with gabapentin, lamotrigine, and levetiracetam also first line. For
      childhood absence epilepsy, ethosuximide was treatment of choice, with valproate
      and lamotrigine also first line. For juvenile absence epilepsy, valproate and
      lamotrigine were treatments of choice. For juvenile myoclonic epilepsy in
      adolescent males, valproate and lamotrigine were treatments of choice, with
      topiramate also first line; for juvenile myoclonic epilepsy in adolescent
      females, lamotrigine was treatment of choice, with topiramate and valproate other
      first-line options. As initial therapy for neonatal status epilepticus,
      intravenous phenobarbital was treatment of choice, with intravenous lorazepam or
      fosphenytoin also first line. As initial therapy for all types of pediatric
      status epilepticus, lorazepam was treatment of choice, with intravenous diazepam
      also first line. For generalized tonic-clonic status epilepticus, rectal diazepam
      and fosphenytoin were also first line; for complex partial status epilepticus,
      fosphenytoin was also first line; and for absence status epilepticus, intravenous
      valproate was also first line. CONCLUSION: The expert panel reached consensus on
      many treatment options. Within the limits of expert opinion and with the
      understanding that new research data may take precedence, the experts'
      recommendations provide helpful guidance in situations where the medical
      literature is scant or lacking. The information in this report should be
      evaluated in conjunction with evidence-based findings.

PMID- 16615563
TI  - [Complications in cochlear implantation].
AB  - OBJECTIVE: The objective [corrected] of this paper is to present the surgical
      complications in cochlear implant, in a serie of 346 patients, submitted to
      surgery by the same surgical team with the subsequent control and follow-up for a
      long period of time. We show the description and the handling of each
      complication. MATERIAL AND METHODS: A follow-up was carried out on 346 cochlear
      implant patients by the same surgical team, from February 1993 to March 2004. The
      complications were assessed and their handling and follow-up is reported. The
      series includes 211 children and 135 adults. RESULTS: The complication rate was
      9.8% (n = 34). The complications found were: Intraoperatory Complications:
      Cerebrospinal Fluid Leaks (CSF), 7; Facial nerve injury, 1; excessive thinning of
      the posterior wall, 2; inmediate post operatory complications: infection of the
      surgical wound, 4; post operatory persistent pain, 1; Tinnitus, 2; late
      complications: Mastoiditis, 2; extrusion of the stimulating receptor, 1; facial
      nerve stimulation, 5; late infections of the stimulation receptor, 2; technical
      failure of the implanted system, 7. Neither alteration or migration was found in
      the receptor placing. CONCLUSIONS: The cochlear implant surgery has a low
      morbility. We found no cases of meningitis due to this procedure.

PMID- 16615564
TI  - [Meniere's disease and migraine].
AB  - INTRODUCTION: The possible link between vertigo and migraine has been known for a
      long time as well as its association with Meniere's disease. OBJECTIVE: To
      determine the lifetime prevalence of migraine in EM patients and to compare it
      with the prevalence of migraine in general population according to the
      International Headache Society (IHS) criteria. METHODS: We interviewed 65 EM
      patients. Our results have been compared with a sex- and age-matched control
      group with no otological antecedent. RESULTS: The lifetime prevalence of migraine
      was significantly higher in Meniere group compared to the age- and sex-matched
      control group (35.4% versus 15.4%, p < or = 0.05). Nine patients with EM and
      migraine related an evident relationship between their vertigo episodes and the
      migraine. CONCLUSIONS: The results obtained in our study suggest the possibility
      of common pathophysiological mechanisms to both pathologies and it may lead to
      new therapeutic options for treatment of EM and migraine patients.

PMID- 16615565
TI  - [Topical liquid nasal gel, its anatomical distribution and transport].
AB  - The objectives of this study are: 1) to assess the anatomical distribution of a
      topical liquid nasal gel in patients with and without rhinitis using a metered
      dose nasal pump, and 2) to determine whether the distribution pattern is
      influenced by dosage and delivery technique. Thirty-nine volunteers were
      evaluated, 26 without nasal inflammation and 13 with rhinitis. Patients self
      administered the nasal spray according to the specifications in one fossa and
      incorrectly in the other one (sniffing and double doses). The findings showed
      that the nasal gel delivered by spray did not penetrate beyond the inferior part
      of the middle turbinate, regardless of delivery technique (double dose with
      sniffing or single dose without sniffing) and the presence or absence of
      inflammation.

PMID- 16615566
TI  - [Evaluation of efficacy and clinical impact of positron emission tomography with
      18F fluoro-deoxyglucose (FDG) in patients with suspicion of recurrent laryngeal
      carcinoma].
AB  - AIMS: To evaluate the efficacy and clinical impact of FDG-PET in patients with
      suspected recurrent laryngeal carcinoma. MATERIALS AND METHODS: 15 patients, with
      suspicion of recurrent laryngeal carcinoma and ambiguous conventional imaging
      modalities. In all patients a whole body scan was performed with FDG-PET in
      fasting patients following i.v. administration of 370-444 MBq FDG. The results
      were confirmed by histology and clinical evolution (follow-up period > 12
      months). RESULTS: Prevalence of recurrence was 86.6%. FDG-PET was positive in 13
      patients, with confirmation in all cases, and 2 were true negative (TN). Overall
      sensitivity, specificity, PPV, NPV and accuracy were 100%. FDG-PET changed the
      modality of treatment in 10 patients (clinical impact 63.3%). CONCLUSIONS: FDG
      PET has high clinical impact in patients with a suspicion of recurrent laryngeal
      carcinoma, and should be incorporated to the diagnostic protocols before making a
      therapy decision.

PMID- 16615567
TI  - [Predictive biochemical indicators of a postlaryngectomy pharyngocutaneous
      fistula: a clinical study].
AB  - The aim of this clinical study was to determinate biochemical predictor
      indicators of postlaryngectomy pharyngocutaneous fistula. PATIENTS AND METHODS:
      We have studied 100 patients with T2- 4 a laryngeal and piryform sinus carcinoma
      who underwent a laryngectomy. All patients were ASA 2-3. We studied serum
      albumin, protein serum level, cholesterol and lymphocites in each patient. These
      variables underwent statistical analysis (p < 0.05). RESULTS: 19% of the patients
      developed a postlaryngectomy pharyngocutaneous fistula, with a long-stay of 25
      days vs. 10 days of stay in patients without postlaryngectomy pharyngocutaneous
      fistula. 7 postlaryngectomy pharyngocutaneous fistula needed surgical repair. Low
      serum albumin (< 3.5 g/dL) and a low level of serum proteins (< 6.5 g/dL) were
      predictive indicators of postlaryngectomy pharyngocutaneous fistula (p < 0.05).
      CONCLUSIONS: Our results suggest that a low-level of serum proteins and albumin
      are predictive clinical parameters of postlaryngeal pharyngocutaneous fistula.

PMID- 16615568
TI  - [Amyloidosis in the ORL field].
AB  - OBJECTIVES: To review the clinical and pathological characteristics of upper
      aerodigestive tract amyloidosis with particular attention to laryngeal
      amyloidosis. Amyloidosis of the upper aerodigestive tract is relatively rare. The
      larynx is the most common site of involvement in head and neck isolated
      amyloidosis and the supraglottic region represents the major site of involvement.
      MATERIAL AND METHODS: Retrospective review of 6 patients diagnosed with upper
      aerodigestive tract amyloidosis. Hoarseness and airway compromise were the main
      presenting symptoms. RESULTS: Laryngeal CO2 laser microsurgery was performed and
      then we refered the patients to the Medical Deparment seeking for systemic
      involvement and ENT Clinic follow up. CONCLUSIONS: In our experience, laryngeal
      CO2 laser microsurgery is a succesfull way to treat isolated laryngeal
      amyloidosis with clinical improvement and low recurrence rates.

PMID- 16615569
TI  - [Sphenochoanal polyp. Diagnostic and therapeutic aspects].
AB  - INTRODUCTION: Sphenochoanal polyps (SCP) grow from the sphenoid sinus and occupy
      the nasopharynx. OBJECTIVE AND RESULTS: To describe the clinical and diagnostic
      features of SCP, reporting two cases. Epidemiological study of the series in the
      literature. 8 published series were found (22 cases). CONCLUSIONS: SCP is a rare
      lesion that is usually misdiagnosed for antrochoanal polyposis. A proper
      diagnosis and surgical treatment are the basis to prevent recurrence. We describe
      the first case of SCP with cacosmia.

PMID- 16615570
TI  - [Kikuchi-Fujimoto disease: report of two cases].
AB  - Kikuchi-Fujimoto disease, described for the first time in 1972, is an unusual
      diagnosis that is characterized by lymph node enlargement and fever. Cervical
      lymph nodes are affected so often that ENT specialists should be aware of this
      entity during differential diagnosis. The diagnosis was done by histological
      features, necrotizing lymphadenitis. The disease is self-limited and it has good
      prognosis. We have reviewed two cases in our hospital. We report an aseptic
      meningoencephalitis as a rare complication.

PMID- 16615571
TI  - Single crystals and nonlinear process for outstanding vibration-powered
      electrical generators.
AB  - This paper compares the performances of vibration-powered electrical generators
      using a piezoelectric ceramic and a piezoelectric single crystal associated to
      several power conditioning circuits. A new approach of the piezoelectric power
      conversion based on a nonlinear voltage processing is presented, leading to three
      novel high performance power conditioning interfaces. Theoretical predictions and
      experimental results show that the nonlinear processing technique may increase
      the power harvested by a factor of 8 compared to standard techniques. Moreover,
      it is shown that, for a given energy harvesting technique, generators using
      single crystals deliver 20 times more power than generators using piezoelectric
      ceramics.

PMID- 16615572
TI  - Modeling of ultrasonic wave propagation in integrated piezoelectric structures
      under residual stress.
AB  - The objective of this study is to understand the role of residual stress in
      piezoelectric layers in order to predict the performance of integrated
      structures. This is of particular importance in thick or thin film technology.
      Considering a bulk piezoelectric material, the Christoffel equation for a
      piezoelectric material is modified to take into account a uniform residual stress
      on a given cross section. A numerical study of its influence is carried out on
      the slowness curves and coupling coefficients of a lithium niobate material. In a
      second part, modified Christoffel tensor is used to calculate the dispersion
      curves of Lamb waves in a piezoelectric plate. The Lamb modes are found to be
      sensitive to the residual stress. In particular, it is shown how the behavior of
      the first Lamb modes is modified with residual stress. In a third part, these
      results are extended to a piezoelectric film laid down on a substrate in order to
      model the importance of these phenomena on the behavior of an integrated
      structure. The numerical study of guided waves in a lithium niobate plate is
      performed first, then the case of a lithium niobate film laid down on a silicon
      substrate is considered.

PMID- 16615573
TI  - Vibration of micromachined circular piezoelectric diaphragms.
AB  - Electrically and mechanically excited resonances in micromachined circular
      piezoelectric diaphragms have been investigated. The diaphragm structures were
      piezoelectric unimorphs consisting of Pb(Zr0.52,Ti0.48)O3 (PZT) films and
      thermally grown silicon oxide (SiO2) layers. For electrical excitation, ring
      shaped interdigitated (IDT) electrodes formed on the top of the PZT layer were
      used to induce strain in the diaphragms. The diaphragm structures behaved much
      like circular membranes in which the membrane tension was approximately 206 N/m,
      at the fundamental modes. For higher modes, the resonance frequencies deviated
      from the theoretical values due to the finite stiffness of the diaphragms. Under
      mechanical drive, both symmetric and asymmetric modes were excited. However, for
      electrical excitation, the symmetric modes were dominant due to the symmetry of
      the driving IDT electrodes. At a pressure of 727 Torr, the quality factor was
      approximately 250, and this rose to 2000 at pressures below 1 Torr. When a
      forward bias was applied to the diaphragm, the membrane tension decreased, but
      under reverse biases the tension increased. However, because of repoling under
      reverse biases greater than the coercive field of the PZT film, the achievable
      increase in the membrane tension was limited. In the diaphragm structure, the
      nonlinear vibration was governed by geometric nonlinearity rather than material
      nonlinearity. In addition, evidence of non-180 degrees domain wall motion of the
      PZT layer in released diaphragms was observed.

PMID- 16615574
TI  - Phase-noise reduction in surface wave oscillators by using nonlinear sustaining
      amplifiers.
AB  - Nonlinear sustaining amplifier operation has been investigated and applied to
      high-power negative resistance oscillators (NRO), using single-port surface
      transverse wave (STW) resonators, and single-transistor sustaining amplifiers for
      feedback-loop STW oscillators (FLSO) stabilized with two-port STW devices. In all
      cases, self-limiting, silicon (Si)-bipolar sustaining amplifiers that operate in
      the highly nonlinear AB-, B-, or C-class modes are implemented. Phase-noise
      reduction is based on the assumption that a sustaining amplifier, operating in
      one of these modes, uses current limiting and remains cut off over a significant
      portion of the wave period. Therefore, it does not generate 1/f noise over the
      cut-off portion of the radio frequency (RF) cycle, and this reduces the close-in
      oscillator phase noise significantly. The proposed method has been found to
      provide phase-noise levels in the -111 to -119 dBc/Hz range at 1 KHz carrier
      offset in 915 MHz C-class power NRO and FLSO generating up to 23 dBm of RF-power
      at RF versus dc (RF/dc) efficiencies exceeding 40%. C-class amplifier design
      techniques are used for adequate matching and high RF/dc efficiency.

PMID- 16615575
TI  - Sol-gel transition in agar-gelatin mixtures studied with transient elastography.
AB  - Using the shear wave propagation in solids, the transient elastography technique
      has been developed to assess the elastic properties of soft tissues. Here, a new
      approach of transient elastography allows assessing the viscoelastic properties
      of soft tissues. In this paper, the method is used to follow-up the sol-gel
      transition of an agar-gelatin mixture noninvasively. The shear wave velocity and
      shear wave attenuation through the mixture were continuously monitored in the
      audible range of frequencies (from 50 Hz to 200 Hz). The observed changes in
      velocities and attenuations as a function of frequency confirmed the validity of
      the Voigt's model to describe the gel at its stable mechanical state. By a simple
      inverse problem approach, based on the one-dimensional (1-D) Helmholtz equation,
      the elasticity and the viscosity of such a mixture were recovered as a function
      of time. The results obtained are in good agreement with the literature and
      theoretical predictions. Overall, they demonstrate the high sensitivity of the
      transient elastography measurements to the rheological parameter changes in agar
      gelatin mixtures during gelation.

PMID- 16615577
TI  - Noise reduction for doppler ultrasound signal based on the adapted local cosine
      transform and the garrote thresholding method.
AB  - In this paper, a novel approach, using the adapted local cosine transform
      combined with the non-negative garrote thresholding, is proposed to remove noise
      from the Doppler ultrasound signal. In the proposed approach, the local cosine
      transform is first performed on the signal of interest followed by a search
      algorithm to select the best basis. Then the coefficients of the obtained best
      basis are thresholded based on the non-negative garrote thresholding method. By
      means of the thresholded coefficients of the best basis, the signal is
      reconstructed. In the simulation study, the estimation precisions of the mean
      frequency waveform and the spectral width waveform are studied for the signal
      after denoising. The simulation and clinical results have shown that the proposed
      approach is superior to ones based on the wavelet transform, especially under low
      signal-to-noise ratio (SNR) circumstances.

PMID- 16615578
TI  - Evaluation of the effect of preload force on resonance frequencies for a
      traveling wave ultrasonic motor.
AB  - In this paper, a novel method of numerical computation of the natural
      frequencies, depending on the most important running parameters for an ultrasonic
      motor, is described. The analyzed configuration by the Space Division of Alenia
      Spazio, Rome, within an Italian Space Agency (ASI) development program, is the
      flexural traveling wave one. The dynamic equations for the stator and the rotors
      of the ultrasonic motor are assumed into a differential system, whose equations
      are coupled by terms that represent interface generalized forces. In order to
      calculate natural frequencies of the motor-coupled terms of the equations are
      worked out with respect to the variables of the degrees of freedom. Hence, the
      mass, damping, and stiffness matrix for the whole system are obtained, then
      resonance frequencies, depending on the most important running parameters such as
      axial preload of the motor, are calculated. The results are compared with
      numerical ones, obtained by a finite element modeling (FEM) model, showing a good
      agreement.

PMID- 16615576
TI  - Modeling and phantom studies of ultrasonic wall shear rate measurements using
      coded pulse excitation.
AB  - Wall shear rate (WSR) is the derivative of blood velocity with respect to vessel
      radius at the endothelial cell (EC) surface. The product of WSR and blood
      viscosity is the wall shear stress (WSS) that has been identified as an important
      factor for atherosclerosis development. High echo signal-to-noise ratio (eSNR)
      and high spatial resolution are crucial for minimizing the errors in WSR
      estimates. By transmitting coded pulses with time-bandwidth product greater than
      one, high eSNR from weak blood scatter can be achieved without increasing
      instantaneous power or sacrificing spatial resolution. This paper summarizes a
      series of measurements in a straight tube (5-mm diameter), constant velocity flow
      phantom using a 10 MHz transducer (60% bandwidth, f/1.5) imaged with a 72 degrees
      Doppler angle, 125 MHz sampling frequency and 1 kHz pulse repetition frequency.
      Measurements were made using a frequency-modulated (FM) code, phase-modulated
      (PM) codes, and uncoded broadband and narrow band pulse transmissions. Both
      simulation and experimental results show that coded-pulse excitation increases
      accuracy and precision in WSR estimation for laminar flow over a broad range of
      peak velocity values when compared to standard pulsing techniques in noise
      limited conditions (eSNR < 30 dB). The code sequence and its length are selected
      to balance range lobe suppression with eSNR and echo coherence enhancements to
      minimize WSR errors. In our study, the combination of an eight bit Optimal coded
      pulse with a Wiener compression filter yielded the highest WSR estimation
      performance.

PMID- 16615579
TI  - Laser ultrasound measurement and finite-element simulation on the dispersion
      behaviors of acoustic waves propagating along wedges with bilinear cross
      sections.
AB  - In this research, dispersion behaviors of antisymmetric flexural (ASF) modes
      propagating along the tip of a bilinear wedge (BW) are investigated. A BW has a
      cross section with two apex angles, as opposed to a linear wedge (LW) whose cross
      section has a single apex angle. In the literature, many studies regarding the
      dispersion behaviors of ASF modes have been reported for LWs, but not for BWs. In
      this study, laser ultrasonic measurements and finite-element numerical
      simulations are used to investigate the dispersion behavior of BW-ASF modes. It
      was found that a BW-ASF mode arises as a result of mode coupling between two LW
      ASF modes of the same order corresponding to the two apex angles of the BW.

PMID- 16615580
TI  - Measurement of low-frequency ultrasonic wave in water using an acoustic fiber
      sensor.
AB  - An acoustic fiber sensor for measurement of ultrasonic waves, which used the
      approximate Raman-Nath diffraction effect where light diffraction waves were
      generated in an optical fiber by strain due to the ultrasonic waves, was proposed
      and examined. In order to characterize the acoustic fiber sensor as a basic
      study, measurements of low-frequency ultrasonic waves in water were examined
      using a step index fiber operating as a detection sensor. The results showed that
      characteristics of detected signals agreed with the theoretical prediction based
      on Fraunhofer diffraction. This indicates that our proposed fiber sensor can be
      used for the detection of low-frequency ultrasonic waves as well as the
      transmission of light diffraction signals.

PMID- 16615581
TI  - The application of time-frequency analysis to the air-coupled ultrasonic testing
      of concrete.
AB  - Air-coupled ultrasound has been used for the nondestructive evaluation of
      concrete, using broad bandwidth electrostatic transducers and chirp excitation.
      This paper investigates the benefits of using time-frequency analysis in such
      situations, for both waveform retrieval and imaging in the presence of low signal
      levels. The use of the short-term Fourier transform, the Wavelet transform, and
      the Wigner-Ville distribution all are considered, in which accurate tracking of
      the ultrasonic chirp signals is demonstrated. The Hough transform then is applied
      as a filter. An image of a steel reinforcement bar in concrete has been produced
      to illustrate this approach.

PMID- 16615582
TI  - On the development and testing of a guided ultrasonic wave array for structural
      integrity monitoring.
AB  - The prototype of a guided ultrasonic wave array for the structural integrity
      monitoring of large, plate-like structures has been designed, built, and tested.
      The development of suitably small transducers for the excitation and measurement
      of the first antisymmetric Lamb wave mode Ao is described. The array design
      consists of a ring of 32 transducers, permanently bonded to the structure with a
      protective membrane, in a compact housing with the necessary multiplexing
      electronics. Using a phased addition algorithm with dispersion compensation and
      deconvolution in the wavenumber domain, a good dynamic range can be achieved with
      a limited number of transducers. Limitations in the transducer design and
      manufacture restricted the overall dynamic range achieved to 27 dB. Laboratory
      measurements for a steel plate containing various defects have been performed.
      The results for standard defects are compared to theoretical predictions and the
      sensitivity of the array device for defect detection has been established.
      Simulated corrosion pitting and a defect cut with an angle grinder simulating
      general corrosion were detected.

PMID- 16615584
TI  - Ultramultiple roundtrips of surface acoustic wave on sphere realizing innovation
      of gas sensors.
AB  - A thin beam of wave usually diverges due to diffraction, which is a limitation of
      any device using such waves. However, a surface acoustic wave (SAW) on a sphere
      with an appropriate aperture does not diverge but is naturally collimated,
      realizing ultramultiple roundtrips along an equator of the sphere. This effect is
      caused by the balance between diffraction and focusing on a spherical surface,
      and it enables realization of high-performance ball SAW sensors. The advantage of
      ball SAW is most fully appreciated when applied to a very thin sensitive film for
      which the multiple-roundtrip enhances the sensitivity, but the attenuation loss
      is not very large. It is exemplified in a hydrogen gas sensor that realizes a
      wide sensing range of 10 ppm to 100% for the first time, and realizes relatively
      fast response time of 20 s without heating the sensitive film.

PMID- 16615583
TI  - DNA immobilization and SAW response in ZnO nanotips grown on LiNbO3 substrates.
AB  - DNA immobilization enhancement is demonstrated in a structure consisting of ZnO
      nanotips on 128 degrees Y-cut LiNbO3. The ZnO nanotips are grown by metalorganic
      chemical vapor deposition (MOCVD) on the top of a SiO2 layer that is deposited
      and patterned on the LiNbO3 SAW delay path. The effects of ZnO nanotips on the
      SAW response are investigated. X-ray diffraction and scanning electron microscopy
      are used to analyze the ZnO nanotips, which are of single crystalline quality,
      and they are uniformly aligned with their c-axis perpendicular to the substrate
      surface. The photoluminescence (PL) spectrum of the ZnO nanotips shows strong
      near bandedge transition with insignificant deep level emission, confirming their
      good optical property. DNA immobilization enhancement is experimentally validated
      by radioactive labeling tests and SAW response changes. The ZnO nanotips enhance
      the DNA immobilization by a factor of 200 compared to ZnO film with flat surface.
      DNA hybridization with complementary and noncomplementary second strand DNA
      oligonucleotides is used to study the selective binding of the structure. This
      device structure possesses the advantages of both traditional SAW sensors and ZnO
      nanostructures.

PMID- 16615585
TI  - New equivalent lumped electrical circuit for piezoelectric transformers.
AB  - A new equivalent circuit is proposed for a contour-vibration-mode piezoelectric
      transformer (PT). It is shown that the usual lumped equivalent circuit derived
      from the conventional Mason approach is not accurate. The proposed circuit, built
      on experimental measurements, makes an explicit difference between the elastic
      energies stored respectively on the primary and secondary parts. The experimental
      and theoretical resonance frequencies with the secondary in open or short circuit
      are in good agreement as well as the output "voltage-current" characteristic and
      the optimum efficiency working point. This circuit can be extended to various PT
      configurations and appears to be a useful tool for modeling electronic devices
      that integrate piezoelectric transformers.

PMID- 16615586
TI  - High power universal piezoelectric transformer.
AB  - This study describes a multilayer piezoelectric voltage and power transformer
      that has one direction poling, operates in a wide-frequency range and delivers
      both step-up and step-down voltages by inverting the electrical connections. In
      this design, the input and output electrodes are on the same side of the disk and
      are isolated from each other by a fixed isolation gap. The electrode pattern is a
      ring/dot structure such that it uses radial mode for both input and output part
      that are built-in on the same ceramic disk. A prototype transformer was
      fabricated of size 15 x 2.78 mm2 having mass of 3.8 gm. In the step-down
      configuration at the constant output power of 6 W, the transformer
      characteristics across a 100 ohms load were found to be efficiency = 92%, gain =
      0.21 input voltage = 110 Vrms, and temperature rise = 20 degrees C from the room
      temperature. In the step-up configuration at the constant output power of 5 W,
      the transformer characteristics across a 5 kohms load were found to be efficiency
      = 97%, gain = 9.5, input voltage = 16 Vrms, and temperature rise = 8 degrees C
      from the room temperature. A detailed equivalent circuit analysis of the
      transformer was done, and the results were found to be in excellent agreement
      with the experimental results.

PMID- 16615587
TI  - The importance of spreading the word about hearing loss.

PMID- 16615588
TI  - Exostosis of the external auditory canal.

PMID- 16615589
TI  - Maxillary sinusitis caused by nasoseptal obstruction.

PMID- 16615590
TI  - Vocal fold hemorrhage observed during laryngoscopy.

PMID- 16615591
TI  - Retained hypodermic needles in the neck.

PMID- 16615592
TI  - Pituitary adenoma.

PMID- 16615593
TI  - Rhinoplasty for the aging nose.

PMID- 16615594
TI  - Written office policies.

PMID- 16615595
TI  - Radiation-induced carotid artery stenosis.

PMID- 16615596
TI  - An innovative method of facilitating ranula excision with methylene blue
      injection.

PMID- 16615597
TI  - A study of the effects of cellular telephone microwave radiation on the auditory
      system in healthy men.
AB  - We conducted a study of the effects of mobile cellular telephone microwave
      radiation on the auditory system in 20 healthy men. After the subjects underwent
      baseline measurements of transient evoked otoacoustic emission (TEOAE) and
      auditory brainstem response (ABR), they participated in three sessions of
      exposure to an electromagnetic field of 900 to 1,800 MHz produced by a cellular
      phone. Sessions ranged from 15 to 30 minutes in length. TEOAE and ABR were again
      measured after or during each exposure. Throughout the study, no significant
      changes in either measurement were noted. We conclude that the use of cellular
      phones does not alter the auditory system in the short-term.

PMID- 16615598
TI  - An unusual site of a CSF leak following resection of a retrosigmoid acoustic
      neuroma.
AB  - Cerebrospinal fluid (CSF) leaks may occur after acoustic neuroma resection. These
      leaks are usually the result of an iatrogenic injury during removal. The
      retrosigmoid approach is commonly associated with leaks that occur through the
      lateral end of the internal auditory canal, through the perilabyrinthine cells
      extending to the region of the internal auditory canal, or through the
      retrosigmoid air cells. We describe a case of an infracochlear CSF leak that
      developed following the retrosigmoid resection of an acoustic neuroma. To the
      best of our knowledge, this leak was unique for both its location and etiology.

PMID- 16615599
TI  - Review of nasopharyngeal carcinoma.
AB  - We review the literature on nasopharyngeal carcinoma that has been published
      within the past 5 years. Nasopharyngeal carcinoma is a highly morbid disease, and
      survival is poor. Its management remains extremely difficult, not just for
      otolaryngologists but for radiation oncologists and medical oncologists, as well.
      A clear understanding of its etiology is still lacking, but nasopharyngeal
      carcinoma is widely suspected to be the result of both a genetic susceptibility
      and exposure to environmental factors or Epstein-Barr virus infection. With no
      clear cause, treatment is controversial. For example, an optimal radiation
      regimen has not been determined, reports in the literature regarding the role of
      chemotherapy for advanced disease are conflicting, and treatment of local
      recurrences is unsettled. Still, advances in immunologic research and
      chemotherapy offer hope for better control of the disease. We hope that our
      assessment of the recent literature will provide otolaryngologists with a more
      clear understanding of the etiology and management of nasopharyngeal carcinoma.

PMID- 16615600
TI  - A study of the link between gastric reflux and chronic sinusitis in adults.
AB  - Much discussion is taking place regarding the role of gastric reflux disease in
      the development and maintenance of chronic sinus disease. We studied 31 patients
      in a large urban private practice who had recalcitrant chronic sinusitis despite
      aggressive medical and surgical therapy. After we obtained information on the
      severity of each patient's sinus disease, we performed either double- or triple
      catheter probe pH testing to assess the presence of reflux disease. Of the 30
      patients who were successfully tested (1 patient did not tolerate probe testing),
      25 demonstrated reflux disease, including 2 whose reflux reached the level of the
      nasopharynx. These 25 patients were placed on a proton-pump inhibitor (PPI)
      regimen and reassessed at least 1 month later. At follow-up, 14 of 15 evaluable
      patients demonstrated at least some improvement in their sinus symptoms,
      including 7 who experienced either a complete or almost-complete resolution of
      symptoms. The improvements in sinus symptoms corresponded with improvements in
      reflux symptoms. These findings suggest that antireflux therapy might play a role
      in the treatment of recalcitrant chronic sinus disease.

PMID- 16615601
TI  - Acute external laryngotracheal trauma: diagnosis and management.
AB  - Laryngotracheal trauma may result in lifelong complications or even death if
      diagnosis or treatment is delayed. Emergency room physicians, trauma surgeons,
      anesthesiologists, and especially otolaryngologists should maintain a high level
      of awareness of and suspicion for laryngotracheal trauma whenever a patient
      presents with multiple trauma in general or with cervical trauma in particular.
      Although there is some controversy regarding care, treatment in experienced hands
      will usually result in a favorable outcome. In this article, we review and update
      the diagnosis and management of acute external laryngotracheal trauma.

PMID- 16615602
TI  - Lower-extremity liposarcoma metastatic to the larynx: case report.
AB  - Distant metastases to the larynx are rare. We describe the case of a 46-year-old
      man who was referred to our head and neck surgery clinic with a 6-week history of
      sore throat and otalgia. He was found to have a laryngeal lesion that was
      consistent with a primary myxoid liposarcoma that had been extirpated from a
      lower extremity earlier To the best of our knowledge, no case of myxoid
      liposarcoma metastatic to the larynx has been previously reported in the English
      language literature.

PMID- 16615603
TI  - Complete esophageal stenosis secondary to peptic stricture in the cervical
      esophagus: case report.
AB  - Complete esophageal stenosis secondary to peptic stricture in the upper esophagus
      is rare. It is, however a serious medical problem that may require
      otolaryngologic intervention because of life-threatening dysphagia and weight
      loss. We report the case of an elderly patient who presented with an upper
      esophageal stricture, without the typical symptoms of gastroesophageal reflux
      disease, that progressed to complete esophageal obstruction despite use of proton
      pump inhibitors and esophageal dilatation. Definitive management of this
      difficult problem required esophagectomy and gastric pull-up. We discuss the
      pathophysiology, clinical presentation, differential diagnosis, and
      multidisciplinary management of peptic esophageal strictures. This case
      illustrates the difficulty in managing high peptic strictures.

PMID- 16615604
TI  - Respiratory epithelial adenomatoid hamartoma: a case report.
AB  - Respiratory epithelial adenomatoid (READ) hamartoma is a recently described
      entity characterized by abnormal glandular formations arising from the epithelium
      of the nasal cavity. The etiology of the lesion is unclear and may be secondary
      to either sinonasal inflammation or developmental error. We present a case of a
      54-year-old man with a unilateral nasal mass found to be consistent with READ
      hamartoma upon pathologic review. Although READ hamartomas are thought to be
      rare, awareness of the lesion is important since it may be confused with
      sinonasal adenocarcinoma, leading to overly aggressive treatment. Therefore, READ
      hamartoma should be included in the differential diagnosis of a unilateral nasal
      mass.

PMID- 16615605
TI  - [Novel sources of additional funding for Official Development Assistance (ODA)].

PMID- 16615606
TI  - [Malaria of a traveling writer].

PMID- 16615607
TI  - [A french-speaking institute for tropical medicine in Asia: the IFMT in
      Vientiane, Lao PDR].
AB  - Since the year-2000, a French-speaking Institute for Tropical Medicine (French
      acronym, IFMT) has been operating in Lao PDR through funding provided by the
      Agence Universitaire de la Francophonie. The IFMT is a postgraduate teaching
      centre dedicated to improving skills of health care professionals in clinical
      sciences, epidemiology, public health and management as well as to research and
      health care intervention. These activities are conducted in the capital as well
      as provinces and districts throughout Laos with special focus on priority health
      issues facing developing countries in tropical regions. The IFMT organizes a 4
      semester international course taught in French to medical doctors from Southeast
      Asia, mainly Laos, Cambodia, Vietnam and Southern China, but also from other
      countries. To date, a total of 72 students have graduated from the IFMT. In 2005
      the Institute delivers a master degree. This article describes the course
      objectives and some features of the curriculum. It also presents a general
      overview of health, teaching, and research facilities in Southeast Asia as well
      as of the major challenges now confronting the region.

PMID- 16615608
TI  - [Best way to engage in the fight against AIDS].

PMID- 16615609
TI  - [Drugs: research of the terrain].

PMID- 16615610
TI  - [Overview of endemic treponematoses].
AB  - Endemic treponematoses including yaws, bejel, pinta are distinguished from
      venereal syphilis on the basis of epidemiological characteristics and clinical
      manifestations. They cannot be differentiated by morphological and serological
      methods. A few minor genetic differences have been identified among the
      subspecies (Treponema pallidum sp. pallidum, pertenue, endemicum, carateum).
      Although penicillin therapy is effective, these infectious diseases have yet to
      be eliminated.

PMID- 16615611
TI  - [Fleas and diseases transmissible to man].
AB  - Fleas are wingless insects that parasitize mammals and more rarely birds. They
      are able to jump and may bite people. Adult fleas are hematophagous. The impact
      of fleas on public health is related to their ability to act as vectors for
      transmission of infectious agents during blood meals. The purpose of this article
      is to describe fleas and the diseases that they transmit to humans. Special focus
      is placed on epidemiological aspects.

PMID- 16615612
TI  - [Lithopedion].

PMID- 16615613
TI  - [Cholera epidemic of 2004 in Dakar, Senegal: epidemiologic, clinical and
      therapeutic aspects].
AB  - During the cholera epidemic that occurred in Dakar, Senegal in 2004, we treated a
      total of 593 confirmed or suspected cases in our department. The purpose of this
      report is to describe epidemiologic, clinical, bacteriologic and therapeutic
      aspects of these cases. Study was conducted at the infectious diseases clinic
      from October 11 to December 20, 2004. Mean patient age was 30 years and the sex
      ratio was 133. The likely source of contamination was food or water intake in 92%
      of cases. The duration of the epidemic was short (75 days). Onset was sudden in
      98% of cases and the main clinical manifestations were watery diarrhoea (95%) and
      vomiting (78%). The mean delay between symptoms and hospitalization was 11 hours
      and the number of stools before admission to the hospital was greater than 10 in
      23% of cases. At the time of admission 119 patients (20.1%) were severely
      dehydrated. A total of 250 coprocultures were performed. Results were positive in
      145 cases (58%) including 112 (44%) for Vibrio cholerae 01. Antibiotic testing
      carried out on 36 strains demonstrated excellent sensitivity to doxycycine and
      pefloxacine but resistance to cotrimoxazole, amoxicilline and chloramphenicol.
      Oral rehydration therapy was used in most cases (61%). The mortality rate was
      0.5%. Cholera is a medical emergency that can have a favourable prognosis with
      properly organized management.

PMID- 16615614
TI  - [Outsourced real-time PCR diagnosis of cutaneous leishmaniasis in the outbreak
      region of Constatine, Algeria].
AB  - Taking into account the re-emergence of leishmaniasis in the world, the
      geographic variability of its epidemiology and the growing numbers of travellers,
      a pilot study on the diagnosis of cutaneous leishmaniasis was undertaken in
      Constatine, one of the outbreak regions in eastern Algeria. A total of 143
      specimens were collected on blotters and tested by real-time PCR. Results were
      compared with those of direct examination. Diagnosis was positive for
      leishmaniasis in 81% of cases using PCR versus 48% of cases using microscopy.
      Real-time PCR showed a significant quantitative difference between patients for
      whom microscopic diagnosis was positive and those for whom direct examination was
      negative. The results presented in this study demonstrated the effectiveness and
      sensitivity of PCR in the diagnosis of cutaneous leishmaniasis from blotter
      specimens. This technique enabled in-field collection of specimens from each
      patient and provided prompt results. North-South cooperation based on the use of
      simple means for transmission of specimens for molecular diagnosis allowed
      creation of an effective partnership for daily diagnosis and promoted exchange
      between investigators in preparation for technology transfer.

PMID- 16615615
TI  - [Influence of social perceptions and practices on the use of bednets in the
      malaria control programme in Ivory Coast (West Africa)].
AB  - The National Malaria Programme in Ivory Coast has encountered difficulty in
      winning public acceptance of insecticide-treated bednets. We speculate that
      resistance to the use of bednets could be rooted in social perceptions, beliefs
      and practices in the communities. The purpose of this study was to identify
      sociocultural and environmental factors that could be used to support promotion
      strategies and acceptance of impregnated bednets in Ivory Coast. Survey findings
      confirmed that bednets were not in widespread use among the population (25%). The
      most widely used methods were burning mosquito coils (50%) and indoor spraying
      (31%). Use of impregnated bednets was low (6%). Most survey respondents (73%)
      indicated initial appreciation for the effectiveness of bednets in protecting
      against mosquitoes as a nuisance. However only 9% of respondents thought that
      impregnated bednets provided protection against malaria although they did not
      necessarily use them. Design was a determinant factor for the use, and even
      acceptance, of bednets. The population want rectangular, permanently impregnated
      bednets large enough to accommodate at least 2 persons. Cost was a major obstacle
      to wider use by the population. According to our data the best price for the
      population would be between 2000 and 2500 FCFA as compared to the current price
      of 3500 FCFA in Ivory Coast.

PMID- 16615616
TI  - [Assessment of a programme of prevention of mother-to-child transmission of HIV
      in Abidjan, Ivory Coast (1999-20002)].
AB  - The purpose of this article is to report the results of a programme for
      prevention of mother-to-child transmission (PMCT) of HIV conducted from 1999 to
      2002 by the PNLS in Abidjan, Ivory Coast. This programme was supported by grants
      from the Fonds de solidarite international (FSTI) and the Glaxo Smith Kline (GSK)
      Foundation. After pre- and posttest counselling, pregnant women from 4 PMI
      centres underwent screening for HIV. Seropositive women were offered short course
      AZT and the possibility of financial assistance for breast-feeding. All programme
      activities were carried out in close cooperation with association members. A
      total of 22466 tests were given and 18116 women returned for results. Among the
      1829 seropositive women to whom PMCT intervention was proposed, 667 received
      short course AZT. The rate of transmission at 18 months was 162%. In addition 69
      mothers and 28 children eligible for ARV therapy benefited from tritherapy.
      Limiting factors, at each phase, and efficacy of intervention were analyzed.

PMID- 16615617
TI  - [Measuring treatment compliance in patients with HIV in Bangui, Central African
      Republic].
AB  - The purpose of this trial was to test a simple method of measuring and
      identifying non-compliance with antiretroviral (ARV) therapy and cotrimoxazole
      (CTX) prophylaxis in a resource-limited setting. A cross-sectional study was
      undertaken among HIV patients attending two outpatient clinics in Bangui, Central
      African Republic. Compliance with ARV and CTX treatment was assessed based on 5
      measurement modalities, i.e., skipping medication during the 4 days prior to
      attendance, attendance assiduity, number of remaining tablets, patient visual
      analogue scale (VAS), and physician VAS. These measures were combined to obtain
      an overall medication compliance score. A total of 141 patients were interviewed
      including 89 using ARV and 52 using CTX. Compliance scores varied according to
      measurement modality from 66.3% to 96.6% for ARV and from 67.3% to 90.4% for CTX.
      The only significant difference between patients using ARV and CTX involved
      physician VAS that was significantly lower for CTX than ARV (p=0.04). Overall
      medication compliance scores classified 117 patients (83%) as compliant and 21
      patients (17%) as non-compliant. According to this study the level of medication
      compliance was relatively good (83%). Findings also indicated that measurement of
      compliance was feasible using a combination of remaining tablet count and
      assessment of medication skipping in the last 4 or 7 days. Routine clinical use
      of these modalities allows assessment and improvement of medication compliance.

PMID- 16615618
TI  - [Prospective study of sexually transmitted infections in Dakar, Senegal].
AB  - The objectives of this study conducted from January to December 2001 at our
      reference centre for sexualy transmitted infections (STI) were to determine the
      epidemiological profile of men who consulted our facility for symptomatic STI,
      describe the clinical manifestations of STI, and propose recommendations for
      improving therapeutic management of STI in tropical areas. A total of 100 men
      consulting for symptomatic STI were included over the one-year study period. In
      addition to administering a standardized questionnaire to each patient, a
      thorough clinical examination especially of the urogenital tract was performed
      and blood and urethral discharge specimens were obtained for analysis at the
      Reference STI laboratory of Institut d'Hygiene Sociale (IHS). Analysis of study
      data demonstrated that the mean age of patients was 25 years, that 52% were
      single, and that level of education was generally low (primary school for 37% and
      secondary school for 27%). However it should be pointed out that 12% of patients
      had a university level education. Most patients were Wolof people living in or
      around Dakar and working in the trades sector (shopkeeper, artists, tailors,
      drivers, and seamen). Thirty-seven percent of patients reported previous STI
      involving urethral discharge in 34% and genital ulcer in 3%. Risk factors
      included sex with random partners in 51% including 31% with prostitutes, more
      than two partners at the time of the study in 34%, and regular alcohol use in
      44%. Neisseria gonorrhoea was by far the most frequent infectious agent found in
      urethral discharge specimens (52%). Genital ulcer was found in only 13 cases.
      Eight of 13 patients with genital ulcers had positive syphilis serology
      suggesting that syphilis was the most frequent aetiology. The other aetiologies
      were uncommon STI, ie., condyloma (n=3), balanitis (n=2), venereal
      lymphogranuloma (n=1) and secondary syphilis (n=1). Serology was positive for HIV
      in 4% of patients. The epidemiologic profile of the patients in our study was
      similar to those previously reported in the literature. However it is interesting
      to note the non-negligible number of cases of STI transmission involving illegal
      prostitution, the high incidence of mismanagement of STI by the health care
      workers who provided initial treatment, the poor availability of drugs used for
      treatment of STI therapy in the centre's Banako Initiative (BI) pharmacy, and the
      frequency of condom non-use by patients with STI.

PMID- 16615619
TI  - [Fauna attacks in French Guiana: retrospective 4-year analysis].
AB  - The rich, diversified fauna of French Guiana has an infamous reputation for its
      aggressiveness. A retrospective analysis of the records the SAMU emergency
      service in Guiana showed that less than 1% of phone calls received between 1998
      and 2001 involved fauna attacks. Most of these calls involved flying hymenoptera
      (36.9%), snakes (15.6 %), dogs (13.8%), and scorpions (9.8%). In 69 of 666 cases,
      the attack was severe enough to warrant dispatching a SMUR intensive mobile care
      unit. These cases involved poisonous snake bites (n=35), flying hymenoptera
      stings (n=24) and scorpion stings (n=5). Although this study presents numerous
      confounding factors, its findings indicate that the risk of fauna attacks in
      French Guiana may be overestimated.

PMID- 16615620
TI  - [Self-treatment of fever in the northern district of Dakar, Senegal].
AB  - Malaria is assimilated with its cardinal symptom, i.e., fever. Treatment of fever
      with antimalarial drugs is crucial to the prevention of malaria-related death in
      Senegal. The objective of this study was to analyze fever-treatment practices as
      a basis for making realistic recommendations for self-treatment in the northern
      health district of Dakar, Senegal. This cross-sectional study was conducted from
      March 1 to April 30, 2003. The population included all patients with body
      temperature higher or equal to 37.5 degrees C (99.5 degrees F) associated with at
      least one of the following symptoms: headache, shivering, vomiting and diarrhoea.
      Study endpoints included demographic data and fever treatment modalities
      including the nature, dosage, and duration of the drugs used. Malaria was
      suspected in 180 of the 271 patients enrolled in the study. Treatment had already
      been undertaken in 134 patients including 108 (81%) who had initiated self
      treatment. Drugs included antipyretics, antibiotics, and/or antimalarials.
      Antimalarial drug dosage was incorrect in 84% of those who initiated self
      treatment. Dosage errors involved number of daily doses (55%), duration of
      treatment (13%), or both (32%). Only 45% of patients fully completed treatment.
      Medical advice was sought in 30% of the cases and drugs were obtained over the
      counter in pharmacies in 59%. Patients under the age of 15 years were
      significantly more likely to initiate self-treatment (p=6.10-6), to treat
      symptoms early, and to use an antimalarial (p=4.10-6). Although self-treatment
      shortened the delay between onset of symptoms and initiation of treatment, it is
      likely that indiscriminate and incomplete treatment is responsible for
      development of resistance to chloroquine in the northern health district of
      Dakar. Strategies must be adapted to numerous local factors influencing self
      treatment including the availability of health-care services and drugs of
      quality. Special attention must be given to the improvement of antimalarial drug
      packaging and of the awareness of people that provide self-treatment drugs.

PMID- 16615621
TI  - [Rectal and colonic injuries induced by enemas: a 10-case series at the
      university hospital center in Bouake, Ivory Coast].
AB  - The purpose of this study is to report our experience in the management of rectal
      and colonic injuries induced by enemas. A retrospective analysis was carried out
      in a series of 10 patients treated at the Bouake, Ivory Coast University Hospital
      Centre for rectal and colonic injuries induced by enemas between January 1, 1997
      and December 31, 2001. There were 6 men and 4 women with a mean age of 26.2 +/-
      5.6 years. Based on history taking five enemas involved criminal intent. The
      other five were carried out for abortion (n=3), therapy (n=1) or autolysis (n=1).
      The injurious product was known in 7 cases, i.e., sulphuric acid (n=4) and hot
      pepper (n=3). The mean quantity administered was 158 +/- 64 ml. The presenting
      picture involved diffuse acute peritonitis in 7 cases and abdominal pain with
      bloody mucoid rectal discharge in 3. One patient died at the time of admission.
      The remaining patients underwent either operative (n=6) or medical (n=3)
      treatment. Prognosis was unfavourable. Four patients died and one patient
      required colostomy that could not be removed due to sclerosis of the anal
      sphincter. Management of rectal and colonic injuries induced by enemas requires
      differential diagnosis to distinguish patients that require emergency laparotomy
      from patients that can be treated medically. For patients treated medically,
      close surveillance based on imaging and repeated clinical examination is of
      paramount importance to allow diagnosis of complications requiring surgical
      treatment.

PMID- 16615622
TI  - [Video-assisted left colectomy for severe constipation. Description of two
      cases].
AB  - The purpose of this report is to describe two cases involving a 43-year-old man
      and a 41-year-old woman who underwent laparoscopic surgery for dolichocolon
      causing severe constipation. In both cases the procedure consisted of left
      colectomy with colorectal anastomosis. There was no operative mortality or
      morbidity. The outcome on constipation was good. This study demonstrates the
      utility of laparoscopy for treatment of dolichocolon in carefully selected
      patents.

PMID- 16615623
TI  - [First reported cases of Streptococcus pyogenes meningitis in Central African
      Republic].
AB  - Streptococcus pyogenes or group A streptococcus is an uncommon cause of bacterial
      meningitis. The purpose of this report is to describe two cases of Streptococcus
      pyogenes meningitis observed in Bangui, Central African Republic. The first case
      occurred in a 44-year-old woman who also presented pyodermitis. The second case
      involved a 34-year-old woman who also presented chronic middle ear infection and
      AIDS. Both strains of Streptococcus pyogenes were classified as biotype group 5
      and showed resistance to tetracycline. They were also T-nontypable and of the emm
      117 genotype and 117.1 subtype. Pulsed-field gel electrophoresis confirmed that
      both strains originated from the same clone.

PMID- 16615624
TI  - [Risk of noscomial infection in intertropical Africa--part 1: background].
AB  - Nosocomial infection is a risk in any health care setting. A review of recent
      medical literature shows that there is a paucity of information on nosocomial
      infection in intertropical Africa. Often misunderstood or denied, nosocomial
      infection is in reality an underestimated public health problem at most medical
      facilities even university hospital centers. However most hospitals are
      confronted with the same financial, structural and logistics difficulties, with
      limited training and awareness about hospital hygiene among caregivers, and with
      situations bringing together contagious infections with susceptible subjects.
      Assessment of the risks for patients and caregivers is a necessary prerequisite
      for implementing measures to control nosocomial infections in intertropical
      Africa.

PMID- 16615625
TI  - [A case of testicular tuberculosis in Antananarivo, Madagascar].

PMID- 16615626
TI  - [Tuberculosis of the tonsil and miliary lung disease].

PMID- 16615627
TI  - [Dengue fever epidemic in Afghanistan: false alarm].

PMID- 16615628
TI  - [Health case functionality in the Velingara health district (Senegal)].

PMID- 16615629
TI  - [Febrile sciatica as the presenting sign of an abscess of the anal rim].

PMID- 16615630
TI  - Automate labs, improve safety.

PMID- 16615634
TI  - Regulation. EMTALA warning.

PMID- 16615635
TI  - Staffing. Public disclosure.

PMID- 16615636
TI  - Facilities. EDs set free.

PMID- 16615637
TI  - Finance. Booking benefits.

PMID- 16615638
TI  - Technology. The real thing.

PMID- 16615639
TI  - Management. Happy workers.

PMID- 16615640
TI  - Finance. Bond protection.

PMID- 16615641
TI  - Staffing. Tuning in to real RNs.

PMID- 16615642
TI  - Data page. Outpatient services and ED visits continue to climb.

PMID- 16615643
TI  - Companies to watch, 2006.

PMID- 16615644
TI  - Just rewards.
AB  - Pay for performance--reimbursing providers for the quality rather than the volume
      of care--seems so logical that it's a wonder it took so long to get here. Initial
      results of pilot programs indicate incentives do spur improvements. However, the
      pilots also point up weaknesses that must be resolved if pay for performance is
      to become the national standard.

PMID- 16615645
TI  - 2006 hospital building report. The boom goes on.
AB  - Our survey of construction trends finds that the most significant expansion and
      replacement of U.S. hospitals since the post-World War II building spree
      continues to fuel a red-hot market. And the building boom is likely to last
      through the rest of the decade.

PMID- 16615646
TI  - Ready for supply inflation?
AB  - Hurricane Katrina was expected to provoke major hikes in the prices that
      hospitals pay for supplies and commodities. But other forces--global demand for
      raw materials and for access to shipping, in particular--are having an even
      bigger impact on everything from heating oil to synthetic gloves. Hospitals are
      using old strategies and creating new ones to try to manage risk and blunt the
      effect of this inflationary spiral.

PMID- 16615647
TI  - Clinical observation units.
AB  - Clinical observation units are emerging as a solution to such pressing problems
      as crowded emergency departments and a lack of inpatient beds. One proponent says
      the units "allow clinicians to provide care better, cheaper and faster".

PMID- 16615648
TI  - Spending on trauma care doubles to dollar 71.6 billion, surpassing heart disease
      and cancer expenditures.

PMID- 16615649
TI  - Providing household help for frail elderly could avert hospitalizations and save
      money on nursing home care.

PMID- 16615650
TI  - You talked, we listened.

PMID- 16615651
TI  - Methodologic issues in the design and analysis of epidemiologic studies of
      pregnancy outcome.
AB  - Using epidemiology to elucidate the causes of adverse pregnancy outcomes offers
      unique opportunities and poses distinctive challenges. The context of pregnancy
      includes contraception and planning, medical interventions altering the natural
      history, and the tendency for selective participation in demanding research
      protocols. Several key pervasive issues are considered in detail: 1) the close
      temporal proximity of determinants and outcomes, which makes separation of causes
      and effects difficult and introduces the real possibility of reverse causality;
      2) non-random allocation of exposure, often done consciously in response to
      concerns about having a healthy pregnancy or to the health of the pregnancy
      itself, making confounding a major concern; 3) heterogeneity of pregnancy
      outcomes, with endpoints such as pregnancy loss and preterm birth arising through
      diverse pathways that are not easily identified and if grouped, could diminish
      the magnitude of observed associations; and 4) racial and ethnic disparities,
      which pose a public health challenge in the USA and offer a potentially important
      opportunity for identifying preventable causes of adverse pregnancy outcome.
      Sophisticated biological and statistical methods are needed to advance
      epidemiologic research in this area.

PMID- 16615652
TI  - Analysis of repeated pregnancy outcomes.
AB  - Women tend to repeat reproductive outcomes, with past history of an adverse
      outcome being associated with an approximate two-fold increase in subsequent
      risk. These observations support the need for statistical designs and analyses
      that address this clustering. Failure to do so may mask effects, result in
      inaccurate variance estimators, produce biased or inefficient estimates of
      exposure effects. We review and evaluate basic analytic approaches for analysing
      reproductive outcomes, including ignoring reproductive history, treating it as a
      covariate or avoiding the clustering problem by analysing only one pregnancy per
      woman, and contrast these to more modern approaches such as generalized
      estimating equations with robust standard errors and mixed models with various
      correlation structures. We illustrate the issues by analysing a sample from the
      Collaborative Perinatal Project dataset, demonstrating how the statistical model
      impacts summary statistics and inferences when assessing etiologic determinants
      of birth weight.

PMID- 16615653
TI  - Design and analysis of time-to-pregnancy.
AB  - Time-to-pregnancy(TTP), the duration that a couple waits from initiating attempts
      to conceive until conception occurs, is regarded as one of the direct measures of
      natural fecundity. Statistical tools for designing and analysing TTP studies
      belong to the general area of survival analysis, but several special features
      have been developed: it is customary to work in discrete time, and random
      heterogeneity between couples has always played a prominent role. This review
      works on this background with focus on how to perform valid analyses, under
      various prospective, retrospective and cross-sectional sampling frames. We
      illustrate using examples from our own experience.

PMID- 16615654
TI  - Heterogeneity in fecundability studies: issues and modelling.
AB  - Modelization of fecundability stepped recently from demography and population
      based contexts to reproductive biology and treatment of infertility. This created
      a strong call for flexibility and robustness. Indeed, explained and unexplained
      heterogeneities are non-negligible sources of bias that result in false
      conclusions as to the determinants of fertility or to the success rates of
      reproductive techniques, among other examples. There are two main sources of
      heterogeneity: biological heterogeneity and heterogeneity of sexual behaviour. A
      uniform presentation of time-to-pregnancy and Barrett-Marshall models is proposed
      to enlighten their similarities and differences in modelling heterogeneity of
      fecundability. Mixed models for fecundability studies are presented as tools to
      allow for unexplained heterogeneity and to quantify heterogeneity of the effect
      of observed factors and variability of size of this unexplained heterogeneity
      between subpopulations. Some criteria for the modelling strategy in fecundability
      studies are suggested with emphasis on the unit-treatment additivity criterion.
      The strong and complex selection process resulting from heterogeneity is
      described as well as the selection and cross-selection processes of observed and
      unobserved fecundability factors. Consequences regarding data collection and
      statistical inference are discussed. In the current context, a consensus setting
      general rules for data collection and statistical analysis would be useful to
      compare the results and increase the reliability of these results in medical
      practice.

PMID- 16615655
TI  - Cervical mucus symptom and daily fecundability: first results from a new
      database.
AB  - With the collaboration of Italian centres providing services on natural family
      planning, a prospective study collected data on 2755 menstrual cycles of 193
      women. A database was constructed using information on the daily characteristics
      of cervical mucus and episodes of intercourse. Taking the day of peak mucus as a
      conventional marker of ovulation, the database identified the length (12 days)
      and location of a 'window' of potential fertility, the highest level of
      conception probability being confined to the central five to six days. Univariate
      analysis provided evidence of the impact on fecundability of the woman's age and
      the basic infertile pattern of a cycle. Several analytical approaches highlighted
      the relationship between daily mucus characteristics and levels of fecundability

PMID- 16615656
TI  - Statistical models for human fecundability.
AB  - Statistical models for fertility studies play a critical role in understanding
      the biology for conception and in identifying potential environmental factors
      that may negatively affect human reproduction. Aided with improved computing
      capability, statistical modeling for fertility data has made a remarkable
      progress in the past decade. The author provides an overview of the historic and
      current developments for fecundability models.

PMID- 16615657
TI  - Estimating causal effects from multiple cycle data in studies of in vitro
      fertilization.
AB  - Prospective studies of reproductive outcomes frequently record data at multiple
      cycles. For example, studies of in vitro fertilization and embryo transfer (IVF
      ET) follow women or couples for possibly several IVF cycles and record outcomes
      such as pregnancy status and embryo implantation. Several time-varying
      covariates, such as age and diagnostic markers, typically are available as well.
      When attention is focused on measurement of exposure effects, the use of multiple
      cycle data poses several complications. If the study is observational, the
      exposure probability may depend on subject characteristics. Moreover, attrition
      rates in IVF-ET can be substantial, and the attrition process can be expected to
      depend heavily on prior outcome. In fact, both success (pregnancy) and failure
      (lack of embryo implantations) can be prognostic of dropout. In this paper, we
      illustrate the use of causal modeling for multiple cycle data. Key assumptions
      are reviewed, and inference based on weighted estimating equations is described
      in detail. The methods are applied to a study of the effects of hydrosalpinx
      among women with tubal disease undergoing IVF-ET.

PMID- 16615658
TI  - Adverse drug reactions reporting at a referral hospital in Zimbabwe.
AB  - OBJECTIVES: To establish factors influencing voluntary reporting of adverse drug
      reactions among health workers. A second objective was to establish the level of
      awareness on adverse drug reaction reporting and attitudes towards the voluntary
      adverse drug reaction reporting scheme. DESIGN: Cross sectional descriptive
      study. SETTING: Parirenyatwa Hospital, a major referral and teaching hospital in
      Harare, Zimbabwe. SUBJECTS: 200 health professionals randomly selected from
      various departments. MAIN OUTCOME MEASURES: Number of health workers reporting
      adverse drug reactions; awareness of the adverse drug reaction reporting scheme.
      RESULTS: 144 (72%) questionnaires were completed. About half (47.2%) of the
      respondents did not know how to report an adverse drug reaction and 47.1% were
      unaware of the existence of a formal adverse drug reaction reporting scheme in
      Zimbabwe. One fifth (20.1%) of the respondents had reported an adverse drug
      reaction at some point. Two main factors contributing to under-reporting cited by
      respondents were the poor feedback from the national reporting centre (59%) and
      inaccessibility of reporting facilities (45.8%). Beliefs that one should only
      report an adverse drug reaction if certain of causality (46.5%) and that really
      serious adverse drug reactions are well documented before a drug is marketed
      (35.4%) could also account for under reporting. However, 75.7%, viewed adverse
      drug reaction reporting as a professional obligation. CONCLUSION: Lack of
      awareness of healthcare professionals to the national (Medicines Control
      Authority of Zimbabwe) adverse drug reaction voluntary reporting scheme, poor
      feedback and inaccessibility of reporting facilities are the main factors
      contributing towards underreporting.

PMID- 16615659
TI  - An experience with surgical admissions to a paediatric ICU (PICU) in Harare,
      Zimbabwe.
AB  - OBJECTIVE: To find out if the status of a patient on arrival in the intensive
      care unit had any bearing on the immediate ICU outcome and if there are any
      correctable factors. DESIGN: A retrospective survey. SETTING: Paediatric
      intensive care unit (PICU) at Parirenyatwa Hospital in Harare, Zimbabwe between
      January 1997 and December 1998. SUBJECTS: 147 emergency surgical admissions.
      RESULTS: There were 147 surgical patients admitted to the PICU during the period
      of whom 77 were male and 43 were emergency surgical procedures. All patients were
      coming from the operating theatres (OT). Factors associated with a poor ICU
      outcome were emergency surgical admission (p<0.001), hypothermia on arrival in
      the PICU (p<0.001) and requirement for ventilation (p<0.001). On multivariate
      analysis only the first two were associated with a poor ICU outcome. CONCLUSION:
      Some simple measures could be undertaken to improve immediate ICU outcome in
      surgical patients in a resource limited environment, such as improving the
      ambient temperature in OT during surgery and standardising transportation to
      PICU.

PMID- 16615660
TI  - Chronic lymphocytic leukaemia (CLL) in Central Africans.
AB  - OBJECTIVE: To document the clinical and haematological features of chronic
      lymphocytic leukaemia (CLL) in Central Africans. DESIGN: Prospective descriptive
      analysis. SETTING: Tertiary referral teaching hospitals. SUBJECTS: 48 Zimbabweans
      and 27 Malawians formed the basis of this analysis. RESULTS: There were 75
      patients (40 males and 35 females) studied and their ages ranged from 32 to 78
      years with a mean +/- s.d. of 56.8 +/- 10.1 years. The peak age incidence of
      26.7% occurred between 60 to 64 year old and 21.3% were below 50 years. The major
      clinical findings included: splenomegaly (68%); hepatomegaly (37.3%); anaemia
      (34.7%); lymphadenopathy (33.3%) and nine (12%) patients were diagnosed
      incidentally. The majority of patients (78.7%) had Rai stage III and IV and only
      seven (9.3%) patients were in stage 0. Of the 32 patients treated with
      chemotherapy, 25.9% and 59.3% achieved complete or partial remissions
      respectively. Six patients were still alive after a follow up period of a mean +/
      s.d of 39.3 +/- 24.4 months; five were lost to follow up after a mean +/- s.d
      period of 28.6 +/- 18.8 months and 16 were dead after a mean +/- s.d. period of
      25.7 +/- 19.1 months. The main causes of death in the treated group were
      septicaemia in six, pneumonia in four and tuberculosis in three. In the untreated
      group of 43 patients, two refused therapy, four died shortly after diagnosis and
      37 were lost to follow up. CONCLUSIONS AND RECOMMENDATIONS: Although the study
      has disclosed that CLL is not rare in central Africans and its presentations are
      similar to cases reported in the literature, the majority of patients seek
      medical treatment late. Optimal therapy is impossible due to lack of chemotherapy
      and supportive services..Therefore, it is recommended that tertiary referral
      centers in African health systems should be equipped for better management of CLL
      patients.

PMID- 16615661
TI  - Making research ethics review work in Zimbabwe--the case for investment in local
      capacity.
AB  - OBJECTIVE: To describe the status of ethics review as pertaining to medical
      research in Zimbabwe, to compare this with international guidelines, and thus to
      identify potential improvements in the process. DESIGN: The description includes
      background about the national review body, the Medical Research Council of
      Zimbabwe (MRCZ), and the findings of an analysis of institutional ethics review
      performed by the MRCZ liaison office. RESULTS: Discrepancies with international
      guidelines include application of the concepts of independent and competent
      review, monitoring of ongoing studies, and ensuring appropriate membership of
      institutional ethics review committees (IRECs). CONCLUSION: A focus on research
      ethics education for researchers and IREC members, as well as ensuring
      appropriate respect for IREC review, are opportunities for improvement in the
      process.

PMID- 16615662
TI  - Further evidence of the usefulness of Acute Physiology and Chronic Health
      Evaluation II scoring system in acute paraquat poisoning.
AB  - OBJECTIVE AND METHOD: We have previously successfully applied the Acute
      Physiology and Chronic Health Evaluation (APACHE) II system to assess the
      severity of patients with acute paraquat poisoning, and this article investigates
      further evidence of the usefulness of APACHE II system in predicting the in
      hospital mortality of 64 patients with acute paraquat poisoning over a period of
      12 years. The predictive factors including APACHE II score, plasma paraquat
      concentration, severity index of paraquat poisoning (SIPP), and estimated
      ingestion dosage of paraquat for evaluating the outcome in paraquat-poisoned
      patients were assessed. RESULTS: Overall mortality was 71.9%: 46 out of 64
      patients died. Non-survivors (n = 46) had a higher APACHE II score (23.3 +/-
      12.7) than survivors (n = 18) (6.1 +/- 4.2) (p < 0.001). The plasma paraquat
      concentration, SIPP, and estimated ingestion dosage of paraquat were
      significantly higher in non-survivors than in survivors (p < 0.05, in all
      comparisons). By multiple logistic regression analysis, only the APACHE II score
      and peak data of blood sugar in 24 h after admission were capable of predicting
      in-hospital mortality. By using the area under receiver operating characteristic
      curves (AURC), the APACHE II system yielded better discriminative power (AURC =
      0.893) than SIPP (AURC = 0.674), plasma paraquat concentration (AURC = 0.676),
      and estimated ingestion dosage of paraquat (AURC = 0.673). An APACHE II score
      greater than 13 predicted in-hospital mortality with 67% sensitivity and 94%
      specificity. CONCLUSIONS: The APACHE II score is a simple, reproducible, and
      practical tool for evaluating the severity of acute paraquat poisoning.

PMID- 16615663
TI  - Toxicoepidemiology in Zimbabwe: admissions resulting from exposure to paraffin
      (kerosene).
AB  - INTRODUCTION: Paraffin (kerosene) ingestion is the most common form of childhood
      poisoning in most developing countries. Despite this, there is a paucity of
      toxicoepidemiological data which could potentially be used in measures to reduce
      preventable exposures. This article reports on the patterns of hospital
      admissions resulting from paraffin exposure in Zimbabwe. METHODS: All cases of
      paraffin ingestion admitted to eight major referral hospitals in Zimbabwe from
      January 1998 to December 1999 (inclusive), were identified using ICD-9 codes and
      ward registers and relevant information recorded on a standard data collection
      sheet. RESULTS: There were a total of 327 admissions due to oral exposure to
      paraffin. This represented 11.8% of all the poisoning admissions to the eight
      study hospitals. Most exposures (300; 91.7%) occurred accidentally, with only
      6.7% resulting from deliberate ingestion of the chemical. The median age on
      admission was 2 years (interquartile range [IQR] 1-2 yrs) with over 85% of cases
      in the 0-5 year age range and less than 10% above the age of 12 years. The median
      age on admission was much higher for deliberate self poisoning (23 yrs; IQR 19-26
      yrs) compared to that for accidental poisoning (1.5 yrs; IQR 1-2 yrs). Accidental
      poisoning from paraffin occurred throughout the year. Over three-quarters of
      patients received an antibiotic either alone, or in combination with another
      antibiotic or drug. Paracetamol (24.3%) was the next most commonly encountered
      treatment. The case fatality rate (CFR) was therefore 0.3 deaths per 100
      admissions (95% Confidence Interval 0.0-1.7). CONCLUSION: Paraffin ingestion
      remains an important cause of poisoning morbidity in Zimbabwe throughout the
      year, particularly in children. Clinical management appears adequate with a low
      mortality, although there may be overuse of prophylactic antibiotics. Further
      study specific to this area is warranted to prevent unnecessary antibiotic use
      and wastage of resources.

PMID- 16615664
TI  - Evaluation of the Be Poison Smart! poison prevention intervention.
AB  - BACKGROUND: Most poisonings to young children are preventable if
      parents/caregivers receive proper education and professional guidance. The Be
      Poison Smart! (BPS) (http:// www.bepoisonsmart.com) train-the-trainer
      intervention was designed to reach healthcare, education, and social service
      providers who impart the BPS message to parents/caregivers of young children.
      METHODS: Using the "Do You Know How to Be Poison Smart!?" Evaluation Tool,
      service providers and parents/caregivers were assessed pre- and 6 weeks post-BPS
      intervention to determine changes in poison prevention knowledge and poison
      prevention behaviors. The dependent variables were pre-post differences in total
      poison prevention knowledge score and in total poison prevention behaviors score.
      Data were analyzed descriptively and using one-way ANCOVA. Effect sizes were also
      calculated. RESULTS: Post-test response rates were 28.7% for the service
      providers (146 out of 509) and 12.4% for parents/caregivers (68 out of 549). The
      mean knowledge score for service providers showed a significant increase of 13%
      (95% Confidence interval (CI) = 8.35%, 17%) from a pre-test mean of 9.4 (total
      possible = 13). Poison prevention behaviors reported by service providers
      significantly improved by 24% (95% CI = 15.6%, 32%) from a pre-test score of 5.7
      (total possible = 11). The mean knowledge score for parents/caregivers
      significantly increased by 16% (95% CI = 7.2%, 24%) from 8.1, and the mean number
      of poison prevention behaviors reported by parents/caregivers significantly
      improved by 11% (95% CI = 3%, 19%) from 6.9. The effect sizes ranged from 0.48 to
      0.69. CONCLUSIONS: The BPS intervention increased the self-reported knowledge and
      behaviors of most participants.

PMID- 16615665
TI  - Formation of methanol and formate in Wistar rats after oral administration of
      methylated rapeseed oil: a fuel for lamps.
AB  - Low viscosity, low surface tension and low volatility are features of lamp oils
      contributing to chemical pneumonia that can occur after ingestion. Because lamp
      oils with such physico-chemical properties have been forbidden in the European
      Community from July 2000 onward, industry has developed different products,
      mostly based upon rapeseed oil. The fatty acids of these oils are methylated. The
      goal of this study is to demonstrate whether methanol is released in Wistar rats
      after oral administration of these new lamp oils. Applying a dose of 1 ml/kg body
      weight lamp oil, peak levels of methanol were reached at 1 h (54.6 +/- 18.6
      microg/ml), methanol was not detectable at 8 h. After the instillation of 4 ml/kg
      of lamp oil peak levels occurred at 2 h (189.2 +/- 24.9 microg/ml). The
      metabolite formate increased with time, and was highest at 8 h after the
      administration of 1 ml/kg body weight lamp oil (32.9 +/- 2.9 microg/ml).
      Starvation before the administration of 1 ml/kg body weight lamp oil decreased
      the methanol serum concentrations, but the differences were not significant.
      Based upon these experimental data in rats, it can be concluded that in humans
      small amounts of methanol will be released after ingestion of these lamp oils. As
      these products are mainly ingested accidentally by toddlers in low quantities,
      the risk of a methanol intoxication seems to be very low.

PMID- 16615666
TI  - Evaluation of several clinical scoring tools in organophosphate poisoned
      patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the Acute Physiology and Chronic
      Health Evaluation (APACHE) II, III and Simplified Acute Physiology Score II (SAPS
      II) as predictors of severity of organophosphate poisoning (OPP). METHODS: This
      is a retrospective study of 48 patients with OPP who were admitted to the
      intensive care unit (ICU) for at least 24 h between 1997 and 2004. Demographic,
      laboratory, survival data and on day one APACHE II, III, SAPS II and Glasgow Coma
      Scale (GCS) were recorded, and correlations between these scores and severity of
      poisoning were performed. RESULTS: Forty-eight patients were evaluated.
      Mechanical ventilation was required by 58% of patients. The mean APACHE II, III
      and SAPS II values were 11.5 +/- 7.21, 42.1 +/- 24.49 and 25.1 +/- 15.76,
      respectively. Total dose and duration of atropine and of pralidoxime therapy,
      length of ICU stay and mortality all correlated with these clinical scoring
      tools. CONCLUSIONS: The APACHE II, III and SAPS II clinical scoring tools seem to
      predict the severity of organophosphate poisoning, and may have prognostic value.

PMID- 16615667
TI  - Clinical vs. laboratory identification of drugs of abuse in patients admitted for
      acute poisoning.
AB  - OBJECTIVE: The extent of drug abuse in patients admitted for self-poisonings is
      uncertain. The aim of this study was to assess the pattern of drugs of abuse
      among patients admitted for acute poisoning according to age and gender, and to
      study the concordance between the clinical assessments by the physicians on duty
      and the drug analyses. METHODS: Prospective cross sectional study of all patients
      (n = 405, 52% males, median age 31 years) treated for acute poisoning in our
      department during one year (2001). The physician on-call classified type of drug
      of abuse by history and clinical assessment. This was later compared to urine and
      blood samples analysed for ethanol, benzodiazepines, opiates, cocaine, ecstasy,
      GHB, amphetamine and cannabis. RESULTS: In 320 admissions (79%), the comparison
      between clinical diagnosis and laboratory analyses could be performed. A total of
      478 drugs were suspected and 621 were found. The main toxic agents found were
      benzodiazepines (49.7%), ethanol (40.3%), opiates (35.3%), cannabis (23.8%) and
      amphetamine (21.3%). Ninety-two had used drugs of abuse. The agreement between
      clinical assessments and laboratory findings was best for GHB and ethanol (kappa
      = 0.43), and for opiates (k = 0.38). For benzodiazepines and cannabis, the
      concordance was poor (k = 0.18 and 0.10, respectively). However, the correct
      clinical evaluation for these substances was 59% and 77%, respectively.
      CONCLUSIONS: Drugs of abuse were more frequently found than suspected clinically.
      Benzodiazepines, ethanol and opiates were most common. The agreement between
      clinical assessment and drug analyses was moderate to low. Physicians seem to
      underestimate the use of these drugs.

PMID- 16615668
TI  - Efficacy of spirulina extract plus zinc in patients of chronic arsenic poisoning:
      a randomized placebo-controlled study.
AB  - BACKGROUND: Millions of people in Bangladesh, India, Taiwan, and Chile are
      consuming high concentration of arsenic through drinking water, and thousands of
      them have already developed chronic arsenic poisoning. There is no specific
      treatment. Some authors suggest the use of vitamins and minerals for more than 6
      months. The present placebo-controlled double-blind study was conducted to
      evaluate effectiveness of spirulina extract plus zinc in the treatment of chronic
      arsenic poisoning. METHODS: Forty-one patients of chronic arsenic poisoning were
      randomly treated orally by either placebo (17 patients) or spirulina extract (250
      mg) plus zinc (2 mg) (24 patients) twice daily for 16 weeks. Each patient was
      supplied with arsenic-safe drinking water by installing a locally made water
      filter at household level. Effectiveness of spirulina extract plus zinc was
      evaluated by comparing changes in skin manifestations (clinical scores), arsenic
      contents in urine and hair, between the placebo- and spirulina extract plus zinc
      treated groups. RESULTS: The concentrations of total arsenic in water (without
      filtration) of placebo- and spirulina extract plus zinc-treated groups were 150.1
      +/- 18.3 and 161.7 +/- 23.9 microg/l, respectively. Intake of these high
      concentrations of arsenic lead to increased excretion of arsenic in urine (72.1
      +/- 14.5 microg/l in placebo-treated group and 78.4 +/- 19.1 microg/l in
      spirulina plus zinc-treated group). After 2 weeks of using filtered water, there
      were significant reduction of both arsenic intake through water and urinary
      arsenic excretion (8.3 +/- 3.6 microg/l and 18.4 +/- 7.3 microg/l in placebo
      group; 9.7 +/- 5.4 microg/l and 21.6 +/- 5.8 microg/l) in spirulina extract plus
      zinc-treated group. There was a sharp increase in urinary excretion of arsenic
      (138 +/- 43.6 microg/l) at 4 weeks following spirulina plus zinc administration
      and the effect was continued for another 2 weeks. Spirulina extract plus zinc
      removed 47.1% arsenic from scalp hair. Spirulina extract had no major adverse
      effect that required physician's attention. The clinical scores (median) for
      melanosis before and after treatment with placebo was not statistically
      significant (p > 0.05), whereas in spirulina extract plus zinc-treated group it
      was statistically significant (p < 0.01). In cases of keratosis, the median
      clinical scores before and after treatment was not statistically significant (p >
      0.05) in placebo-treated group. In spirulina extract plus zinc-treated group, the
      clinical scores for keratosis before and after treatment was statistically
      significant (p < 0.05). CONCLUSIONS: Results show that spirulina extract (250 mg)
      plus zinc (2 mg) twice daily for 16 weeks may be useful for the treatment of
      chronic arsenic poisoning with melanosis and keratosis.

PMID- 16615669
TI  - Seizures associated with intoxication and abuse of tramadol.
AB  - PURPOSE: To assess the frequency of seizures and patient characteristics
      associated with tramadol intoxication and abuse in young addicts. METHODS:
      Patients with history of tramadol abuse and intoxication were prospectively
      studied during a 3-year period. The characterstics of patients with seizures and
      those without seizures were compared. RESULTS: Fifty-seven patients (mean age
      22.3 years [range 16-43 years], 47 males) were included. Tonic/clonic seizures
      occurred in 31 (54.4%) patients, (26 males and 5 females): single in 14 (45%),
      multiple in 17 (55%) patients after a tramadol dose ranging from 250-2500 mg.
      Seizures occurred within 24 h after tramadol intoxication in 26 (84%) patients,
      and later in 5 (16%) patients. Compared to addicts without seizures, the abusers
      with seizures were younger (p < 0.05). Both epileptiform and nonepileptiform
      electroencephalographic patterns were more common in patients with seizures than
      in patients without seizures, but the differences did not reach statistical
      significance. CONCLUSION: The neurotoxicity of tramadol commonly manifests as
      generalized tonic-clonic seizures occurring most frequently within 24 h after
      tramadol intake. Seizures were more common in younger abusers with a longer
      duration of exposure to tramadol and with the combined use of tramadol with
      alcohol.

PMID- 16615670
TI  - Interference by venlafaxine ingestion in the detection of tramadol by liquid
      chromatography linked to tandem mass spectrometry for the screening of illicit
      drugs in human urine.
AB  - Confirmation of the presence of illicit drugs in human fluids by liquid
      chromatography linked to atmospheric pressure ionisation tandem mass spectrometry
      (LC/MS/MS) is becoming increasingly popular. A rapid LC/MS/MS method is described
      using reversed phase gradient elution chromatography on a 50 x 3 mm base
      deactivated C8 column with identification of drugs based on their Multiple
      Reaction monitoring (MRM) transitions, retention time, and co-elution of stable
      isotopic analogues where available. The method is used for drug confirmation
      following initial screening by immunoassay, and identification of drugs such as
      tramadol, for which no immunoassay is available. False positive results for
      tramadol were observed in cases where subjects were being treated with the
      commonly prescribed antidepressant drug venlafaxine. This was a result of the
      presence of the metabolite O-desmethylvenlafaxine, which has a similar transition
      to tramadol. This study highlights the need to consider drug metabolites, as well
      as parent drugs in interferences in LC/MS/MS methods.

PMID- 16615671
TI  - Cytochrome-c oxidase inhibition in 26 aluminum phosphide poisoned patients.
AB  - INTRODUCTION: Aluminum phosphide (ALP) is used worldwide to fumigate grain. ALP
      poisoning, though reported from different parts of world, is most common in
      north, northwest and central India. In the presence of moisture, ALP liberates
      phosphine, which is highly toxic. The mechanism of action of phosphine is not
      known though experimental studies show that it inhibits cytochrome-c oxidase
      leading to inhibition of mitochondrial oxidative phosphorylation. PATIENTS AND
      METHODS: We estimated cytochrome-c oxidase activity in platelets of patients who
      had ingested ALP and compared them with those in healthy controls and in patients
      with shock due to other causes (cardiogenic shock, septic shock and hemorrhagic
      shock). RESULTS: After analysis of variance using Kruskal-Wallis test followed by
      Mann Whitney U test, significant inhibition of cytochrome-c oxidase activity
      could be found in ALP-poisoned patients compared to healthy controls (z = -5.513,
      p < 0.001) and in patients with shock due to other causes (z = -2.344; p < 0.05).
      There was no significant difference in inhibition in those who survived ALP
      poisoning compared to those who died from ALP poisoning (t = 0.02768; p > 0.05).
      CONCLUSION: Though inhibition of cytochrome-c oxidase in platelets does not have
      prognostic value, it suggests that interruption of mitochondrial oxidative
      phosphorylation as a result of cytochrome-c oxidase inhibition may lead to multi
      organ dysfunction and therapeutic strategies to maintain enzyme activity may help
      in managing these patients.

PMID- 16615672
TI  - Visual field defects in epidemic dropsy.
AB  - Epidemic dropsy is a multi-system disease involving the cardiovascular, hepatic,
      renal, ocular and other systems. It is a toxic disease caused by the
      unintentional ingestion of Argemone mexicana (prickly yellow poppy) seeds as an
      adulterant of wheat flour or more commonly of cooking oil such as mustard oil.
      PURPOSE: To investigate the occurrence of visual field defects in patients
      suffering from epidemic dropsy glaucoma. METHODS: Visual field analysis was
      performed to ascertain the field defects, in patients suffering from epidemic
      dropsy. Group I consisted of 35 patients (69 eyes) whose intraocular pressure
      (IOP) was > or = 22 mmHg. Ten dropsy patients (20 eyes) with normal IOP (<22 mm
      Hg) formed Group II. Ten healthy unexposed volunteers (20 eyes) constituted Group
      III. All the patients were tested using the Armaly full field glaucoma screening
      test on the Humphrey field analyzer. RESULTS: Forty seven of the 69 eyes (68%)
      suffering from epidemic dropsy glaucoma, and 18 out of 20 (90%) eyes in dropsy
      patients with normal IOP, showed field defects. In the control group, 15% eyes
      had only nasal field defects. The difference between Group I and II was not
      significant (p = 0.054), though the field defects were significantly more
      frequent in dropsy patients as compared to the controls (p < 0.01 in either
      case). The results suggest that visual field defects in epidemic dropsy occur
      independently of the rise in intraocular pressure. Field defects were detected
      more frequently in patients who underwent visual field analysis early in the
      course of disease, as compared to those who underwent screening later on in the
      disease course. CONCLUSIONS: In epidemic dropsy, acute visual field defects occur
      independent of rise of intraocular pressure and more frequently in the early
      stage of the disease.

PMID- 16615673
TI  - Clinical course and toxicokinetic data following isolated citalopram overdose in
      an infant.
AB  - OBJECTIVE: Despite the frequency of use of citalopram, its clinical effects and
      pharmacokinetics in overdose in the pediatric patient are not well described. We
      describe the clinical course and drug levels following the ingestion of
      citalopram by a 10-month-old female. CASE REPORT: A 10 month-old female ingested
      an unknown amount of citalopram. Approximately 40 min after ingestion, the child
      developed horizontal nystagmus, followed by a generalized, tonic-clonic seizure
      that lasted 2 to 3 min very shortly thereafter. The child received 1 mg of
      midazolam intramuscularly (IM), followed by 1 mg of midazolam intravenously (IV)
      for termination of this seizure, and was given a loading dose of 20 mg/kg of
      fosphenytoin IV. Elective orotracheal intubation was done to protect the airway.
      Despite the use of midazolam and fosphenytoin, the child had another seizure
      approximately 85 min following the ingestion. A third seizure was noted at
      approximately 100 min post-ingestion. In the course of treatment, activated
      charcoal was administered via nasogastric tube, and IV midazolam and
      phenobarbital were given. The child was transferred to a nearby facility with
      pediatric intensive care capabilities in stable condition. The child did not
      experience any hypotension or dysrhythmia, and the electrocardiographic QTc and
      QRS complex were normal throughout the clinical course. During the subsequent 48
      h, the child awoke and regained normal function. This child's recovery was
      uneventful, and the child was discharged home without sequelae. Plasma levels of
      citalopram were 1400 ng/ml, 583 ng/ml, 416 ng/ml, and 296 ng/ml, at one, six, 13,
      and 23 h post-ingestion, respectively. The first level likely represents a
      predistributional level with subsequent levels giving an elimination t1/2 of
      17.38 h. CONCLUSION: We report a case of citalopram poisoning in a 10-month-old
      infant with refractory seizures, and an absence of cardiovascular events with
      subsequent excellent outcome. The elimination of the parent drug corresponds to
      an approximate t1/2 of 15-20 h in this single case.

PMID- 16615674
TI  - Monitoring of verapamil enantiomers concentration in overdose.
AB  - A 52-year-old woman with a history of depression and personality disorders,
      hypertension, coronary disease and asthma was admitted to the Department of
      Clinical Toxicology after taking 60 tablets of Staveran (immediate release
      verapamil), and 4 tablets of acetaminophen. One and a half hours after ingestion
      her condition was critical. She required endotracheal intubation and artificial
      respiration. Her heart rate was 75 beats per minute, (bpm) and her blood pressure
      dropped from 70/50 to 50/00 mmHg. Additionally, drowsiness and headache were
      observed. On admission, R-(+)- and S-(-)-verapamil serum concentrations were 2252
      ng/ml and 810 ng/ ml, respectively. Monitoring of the verapamil serum
      concentration was carried out over 74 h. Terminal elimination half-lives were
      18.7 (21.3) and 17.0 (18.5) hours, respectively, for R-(+)- and S-(-)-verapamil.
      Monitoring of verapamil enantiomers concentrations in serum indicated a higher
      concentration of the less active form and slightly faster elimination of the more
      active enantiomer. The data-support a stereoselective difference between first
      pass clearance and later systemic clearance of verapamil, when taken in overdose.

PMID- 16615675
TI  - Chronic hydroxychloroquine use associated with QT prolongation and refractory
      ventricular arrhythmia.
AB  - BACKGROUND: Hydroxychloroquine (HCQ) is used for treatment of lupus
      erythematosus. The cardiac toxicity of HCQ has focused primarily on acute
      intoxication. We report a case of chronic use of HCQ associated with torsade de
      pointes. CASE REPORT: A 67-year-old female presented with acquired long QT
      interval syndrome with a refractory ventricular arrhythmia. She was receiving
      chronic therapeutic doses of HCQ for the treatment of lupus erythematosus.
      Torsades de pointes was diagnosed in the Emergency Department (ED). After
      excluding other causes of long QT syndrome, the HCQ was suspected as the cause of
      her ventricular tachycardia. After discontinuing the HCQ, the QT interval was
      shorter and the patient recovered after treatment with lidocaine and
      isoproterenol. CONCLUSION: The chronic use of HCQ for rheumatic diseases, or as
      an anti-malarial drug, should be balanced against the risk of developing
      potentially lethal cardiac arrhythmias.

PMID- 16615676
TI  - Renal infarction during the use of rizatriptan and zolmitriptan: two case
      reports.
AB  - Rizatriptan and zolmitriptan are both used to relieve acute migraine and cluster
      headaches. The mechanism of action is similar to the other triptans, in that they
      reverse abnormal cerebral vasodilation through their activity as 5-HT1B receptor
      agonists. Triptan-induced vasoconstriction is attributed to its activity on
      peripheral 5-HT1B receptors and has rarely been reported to result in stroke,
      myocardial infarction and ischemic colitis. We present two cases of renal
      infarction associated with therapeutic triptan use. The first patient is a 57
      year-old man with a history of hypertension that was well controlled on valsartan
      and hydrochlorothiazide. He was recently diagnosed with cluster headaches and was
      treated with indomethacin, prednisone, butalbital-acetaminophen-caffeine and
      hydrocodone without relief. He then received two therapeutic doses of rizatriptan
      on each of the two days prior to presentation. Subsequently, he presented to the
      emergency department complaining of nausea, vomiting and right-sided abdominal
      pain. A computerized tomography (CT) scan of the abdomen and pelvis with
      intravenous contrast revealed a very large wedge shaped infarction of the right
      kidney. The second patient is a 34-year-old man with a past medical history
      significant only for life-long migraine headaches successfully treated for the
      past six years with zolmitriptan. Shortly after taking one therapeutic dose of
      zolmitriptan, he presented to the emergency department complaining of nausea and
      left-sided abdominal pain. A CT scan of the abdomen and pelvis with intravenous
      contrast revealed multiple wedge-shaped infarctions of the left kidney. Renal
      infarction was confirmed in both patients by arteriogram of the renal arteries.
      Although both rizatriptan and zolmitriptan are effective in the treatment of
      migraine and cluster headaches, they may induce peripheral vasospasm leading to
      renal infarction.

PMID- 16615677
TI  - Hyperosmolality: another indication for hemodialysis following acute ethylene
      glycol poisoning.
AB  - When given early, fomepizole has demonstrated an effective role in the treatment
      of ethylene glycol (EG) intoxication, often eliminating the need for hemodialysis
      (HD). Many indications for HD have been suggested for EG intoxication. We present
      a case of EG intoxication with the second highest reported EG concentration.
      Despite early treatment with fomepizole and without the development of acidosis
      or renal insufficiency, the patient required HD for hyperosmolality and
      subsequent electrolyte imbalances. Indications for HD following EG intoxication
      are discussed.

PMID- 16615678
TI  - Hallucinatory fish poisoning (ichthyoallyeinotoxism): two case reports from the
      Western Mediterranean and literature review.
AB  - Ichthyoallyeinotoxism is a rare kind of food poisoning contracted following the
      ingestion of fish. The responsible toxins are unknown, and the clinical feature
      is characterized by the development of CNS disturbances, especially
      hallucinations and nightmares. As the implicated fish species may be also related
      to ciguatera poisoning, there may be possible confusion between the two fish
      borne intoxications. In order to clarify this, the literature pertaining to
      "dreamfish" was reviewed and two cases are presented. A 40-year-old man
      experienced mild digestive troubles and terrifying visual and auditory
      hallucinations after eating a specimen of Sarpa salpa in a restaurant. As he had
      severe behaviour troubles, he was managed in the hospital and recovered 36 h
      after the meal. He was unable to recall the hallucinatory period. Another man, 90
      years-old and previously healthy, had auditory hallucinations 2 h after eating a
      specimen of Sarpa salpa. The two following nights, he had numerous nightmares and
      recovered spontaneously after a period of 3 days.

PMID- 16615679
TI  - Acute occupational poisoning by octogen: first case report.
AB  - BACKGROUND: Octogen (HMX) is a polynitramine explosive closely related to
      hexogen, a known occupational toxin in military munitions plants. No acute human
      poisoning with octogen has ever been reported. CASE REPORT: A 28-year-old man
      with no history of epilepsy was admitted to the Emergency Department for seizures
      that had developed during the night after a full working day when he manually
      sieved large amounts of dry octogen. On admission, the clinical examination was
      normal and all other examinations could not substantiate the development of
      essential or secondary epilepsy. Elevated octogen concentrations were measured in
      his plasma, which confirmed occupational exposure to the explosive. CONCLUSION:
      The rarity of acute human poisonings by octogen is due to the infrequent use of
      this explosive and, more importantly, its very low oral bioavailability. However,
      acute poisoning can occur, but should be easily avoided by implementing adequate
      preventive measures.

PMID- 16615680
TI  - Puffballs...a delicacy if the timing is right.

PMID- 16615681
TI  - Is acidosis commonly seen in patients with elevated ethanol levels?

PMID- 16615682
TI  - Albumin dialysis: a new therapeutic alternative for severe diltiazem
      intoxication.

PMID- 16615683
TI  - A case of Horner's syndrome and delayed polyneuropathy due to dichlorvos
      intoxication.

PMID- 16615684
TI  - A prospective clinical study of cerebral microemboli and neuropsychological
      outcome comparing vent-line and auto-venting arterial line filters: both filters
      are equally safe.
AB  - INTRODUCTION: Microemboli are the main implicated cause of neuropsychological
      (NP) impairment after cardiac surgery. This prospective clinical trial compared
      the effect of an auto-venting arterial line filter on intraoperative cerebral
      microemboli and NP outcome compared to an arterial line filter with a vent line,
      in patients undergoing elective coronary artery bypass graft (CABG) surgery.
      METHODS: One hundred and ten patients received either an Avecor Affinity (n =73)
      or Pall AV-6 (n =37) control filter. Cerebral microemboli during cardiopulmonary
      bypass were recorded by transcranial Doppler monitoring of the right middle
      cerebral artery. Evidence of cerebral impairment was obtained by comparing
      patients' performance in a NP test battery (nine tests) administered 6-8 weeks
      postoperatively with their preoperative scores. RESULTS: During cardiopulmonary
      bypass, the median number and range of microemboli were 67 (5-846) and 55 (2-773)
      for the Avecor and AV-6 groups, respectively (p = 0.47). There was no difference
      in NP outcome. CONCLUSION: There is no difference in the filtering ability of
      vent-line and auto-vent filters as assessed by cerebral microemboli. This,
      together with the similar NP outcome, suggests that both types of filter are
      equally safe for clinical use.

PMID- 16615685
TI  - A recovery model of minimally invasive cardiopulmonary bypass in the rat.
AB  - This study was undertaken to develop a rodent (rat) model of cardiopulmonary
      bypass (CPB) that has been designed to mimic functionally the minimally invasive
      clinical setting. The circuit is similar to the clinical model in terms of its
      construction, configuration, material surface area to blood volume ratio, and
      priming volume to blood ratio. The overall priming volume was 10 mL. Thirty-six
      male Sprague-Dawley rats (422 +/- 32 g) were anaesthetized while maintaining
      spontaneous ventilation. Anticoagulation was achieved with heparin (500 IU/kg).
      Blood arterial pressure was monitored continuously. Normal central temperature
      was maintained throughout. Intermittent arterial blood gas levels also were
      monitored. All animals were cannulated in preparation for CPB; however, CPB,
      utilizing a double roller pump and a flow rate of 100 mL/kg/minute for 60 min,
      was initiated in only 18 animals, the remaining 18 animals acting as non-CPB
      controls (Sham). The animals were haemodynamically stable. After the operative
      procedure, the animals were allowed to recover from the anaesthesia and, after
      transfer to a recovery facility, were monitored for a period of 1 week. There
      were no differences between the groups in terms of blood gas analysis and blood
      pressure data; all animals survived the procedure and had an uneventful follow
      up. Differences were found between the CPB animals and the Sham group in terms of
      TNFalpha used as a marker of inflammatory processes. This trend tends to support
      this model as an analogue for the clinical scenario for future studies of CPB
      related inflammation. Overall, the CPB procedure was easy to perform and was
      associated with excellent survival. This recovery model is an effective tool to
      perform pathophysiological studies associated with minimally invasive CPB.

PMID- 16615686
TI  - Cardiac organ donor management.
AB  - There is a critical shortage of donor organs. According to the United Network for
      Organ Sharing (UNOS), 20% of organs are discarded after procurement. Many of
      these may be potentially salvageable. Brain death is particularly detrimental to
      cardiac function. The initial sympathetic storm can produce direct myocardial
      injury. The ensuing spinal shock reduces global oxygen delivery. There is a
      change to anaerobic metabolism due to global mitochondrial dysfunction. Diabetes
      insipidus worsens hypovolemia and thyroid deficiency impairs cardiac function.
      Inadequate replacement of blood loss from trauma and coagulopathy worsens anemia
      and oxygen delivery. In the mid-1990s, the Papworth Hospital group in the UK
      advocated early invasive hemodynamic monitoring and administration of a 'hormonal
      cocktail', consisting of triiodothyronine (T3), vasopressin, methylprednisolone
      and insulin. This has been widely accepted and is endorsed by UNOS. Ventricular
      function, volume status and adequacy of resuscitation should be guided by
      invasive monitoring and serial echocardiography. Dopamine or epinephrine is used
      for inotropic support. If hypotension persists, vasopressin should be added which
      may allow reduction of inotropes. Donor lung function and ventilation should be
      optimized. Recently, two large retrospective studies have shown that, with
      aggressive pharmacological and hormonal resuscitation, a significant increase in
      the number and quality of organs harvested can be achieved.

PMID- 16615687
TI  - A statistical analysis of factors predisposing patients to heparin resistance.
AB  - Heparin resistance (HR) is occasionally encountered in cardiac surgery. The
      objective of this study is to identify possible factors predisposing patients to
      heparin resistance. Four hundred patients scheduled for elective cardiac surgery
      requiring the use of cardiopulmonary bypass (CPB) were enrolled in this study.
      Data collection included: demographic data, types of preoperative
      anticoagulant/antiplatelet therapy, preoperative haematological and biochemical
      laboratory results, medical condition, baseline activated clotting time (ACT) and
      infusion volume prior to heparinisation. Patients who require 5 mg/kg or more to
      achieve ACT greater than 400 seconds before CPB were considered to be heparin
      resistant. All data was tested with a preliminary univariate analysis and factors
      associated with HR (p value <0.05) were entered into a multivariate logistic
      regression analysis. Factors associated with HR with a p value <0.05 are
      considered predictors for HR. Thirty-two (8.0%) of the 400 patients fulfilled the
      criteria for HR. Preoperative heparin (p =0.025), low molecular weight heparin (p
      =0.049), plateletcount > or = 300,000/ml (p =0.022) and albumin plasma
      concentration < or = 35 g/dl 0, =0.044) are significantly associated with HR. HR
      patients also tend to require more volume replacement prior to CPB to maintain
      haemodynamic stability p=0.007).

PMID- 16615688
TI  - Testing of heat exchangers in membrane oxygenators using air pressure.
AB  - All heat exchangers (HE) in membrane oxygenators are tested by the manufacturer
      for water leaks during the production phase. However, for safety reasons, it is
      highly recommended that HEs be tested again before clinical use. The most common
      method is to attach the heater-cooler to the HE and allow the water to
      recirculate for at least 10 min, during which time a water leak should be
      evident. To improve the detection of water leaks, a test was devised using a
      pressure manometer with an integrated bulb used to pressurize the HE with air.
      The cardiopulmonary bypass system is set up as per protocol. A pressure manometer
      adapted to a 1/2" tubing is connected to the water inlet side of the oxygenator.
      The water outlet side is blocked with a short piece of 1/2" deadend tubing. The
      HE is pressurized with 250 mmHg for at least 30 sec and observed for any drop.
      Over the last 2 years, only one oxygenator has been detected with a water leak in
      which the air-method leaktest was performed. This unit was sent back to the
      manufacturer who confirmed the failure. Even though the incidence of water leaks
      is very low, it does occur and it is, therefore, important that all HEs are
      tested before they are used clinically. This method of using a pressure manometer
      offers many advantages, as the HE can be tested outside of the operating room
      (OR), allowing earlier testing of the oxygenator, no water contact is necessary,
      and it is simple, easy and quick to perform.

PMID- 16615689
TI  - Systemic arterial waveform analysis and assessment of blood flow during
      extracorporeal circulation.
AB  - BACKGROUND: The pressure recording analytical method (PRAM) is a method for real
      time beat-to-beat quantification of peripheral blood flow based on the analysis
      of arterial waveform morphology. Since PRAM can be implemented in any conditions
      of flow, whether physiological or artificial, we assessed its accuracy in
      patients undergoing cardiac surgery during extracorporeal circulation (ECC),
      using the roller-pump device as the reference gold standard. METHODS: We
      prospectively studied 32 patients undergoing elective coronary surgery. Flow
      values obtained by PRAM from the radial artery were compared with simultaneous
      values by thermodilution in physiological conditions of flow and with the roller
      pump device readings during ECC. RESULTS: Before and after ECC, the overall
      estimates of flow measured by PRAM closely agreed with thermodilution (mean
      difference 0.07 +/- 0.40 L/min). During ECC, PRAM estimates of flow also closely
      correlated with simultaneous pump readings (mean difference 0.11 +/- 0.33 L/min).
      At time of weaning from ECC, two patterns of hemodynamic adaptation were
      documented by PRAM following resumption of cardiac contraction: in most patients
      (n =26; 80%), cardiac output (CO) was stable (reduction < or = 10% compared to
      the steady ECC phase); six patients (20%) showed a fall in CO exceeding 10% and
      up to 38%. CONCLUSIONS: PRAM provided accurate, continuous quantification of
      peripheral blood flow during each phase of cardiac surgery, including ECC, and
      allowed early recognition of patients with low CO during weaning from the pump.

PMID- 16615690
TI  - Cardiopulmonary bypass for a coronary artery bypass graft patient with
      heterozygous protein C deficiency and protein S deficiency.
AB  - Cardiopulmonary bypass (CPB) poses great risks for hypercoagulable patients and
      requires management techniques to ensure an optimal outcome free from thrombotic
      events. This case report reviews perfusion management techniques that may
      contribute to a safer CPB experience for a patient deficient in both protein C
      and protein S. A patient with heterozygous protein C deficiency is at increased
      risk of thrombosis, especially in the venous circulation. Since it is an
      essential cofactor for activated protein C, deficiency of free protein S is also
      linked to a hypercoagulable condition. A 52-year-old male presented to our
      institution with a past medical history of hypercoagulable state, multiple deep
      vein thromboses, pulmonary embolisms, and stroke. He was scheduled for two-vessel
      coronary artery bypass graft surgery to be followed by right carotid
      endarterectomy (RCEA) before discharge. The anesthesia and perfusion teams worked
      closely together to ensure that fresh frozen plasma (FFP) was given
      intraoperatively at appropriate times. Heparin dose response and protamine dosage
      was determined with hemostasis management system (HMS) analysis. The closed CPB
      circuit and cannulae were Carmeda bonded. Rapid autologous priming, along with
      the use of a hemoconcentrator, kept the hematocrit above 21 during CPB. Zero
      balance ultrafiltration and leukocyte depletion were initiated during rewarming
      to aid in attenuation of the inflammatory response. To conserve coagulation
      factors, all pump blood was ultrafiltrated post-CPB and returned to the patient.
      Laboratory samples drawn on postoperative day (POD) one measured normal protein C
      activity with subnormal protein S activity. On POD six, the patient underwent
      RCEA and he was discharged on POD eight without complications.

PMID- 16615691
TI  - The use of extracorporeal life support in the treatment of influenza-associated
      myositis/rhabdomyolysis.
AB  - A 13-year-old girl presented to the emergency department with fatigue, headaches
      and muscle stiffness after returning from a family camping trip. Within 24 h, she
      was transferred to ICU with general oedema and low saturations, where she had a
      cardio-respiratory arrest and was placed on veno-arterial extracorporeal membrane
      oxygenation (ECMO). The patient was successfully supported with ECMO for profound
      myocardial dysfunction and haemofiltration for rhabdomyolysis and acute renal
      failure. Patients who present with profound myocardial dysfunction and
      myoglobinuria as a consequence of viral infection can be successfully supported
      with ECMO.

PMID- 16615692
TI  - Climate change and sustainable development: realizing the opportunity.
AB  - Manifold linkages exist between climate change and sustainable development.
      Although these are starting to receive attention in the climate exchange
      literature, the focus has typically been on examining sustainable development
      through a climate change lens, rather than vice versa. And there has been little
      systematic examination of how these linkages may be fostered in practice. This
      paper examines climate change through a sustainable development lens. To
      illustrate how this might change the approach to climate change issues, it
      reports on the findings of a panel of business, local government, and academic
      representatives in British Columbia, Canada, who were appointed to advise the
      provincial government on climate change policy. The panel found that sustainable
      development may offer a significantly more fruitful way to pursue climate policy
      goals than climate policy itself. The paper discusses subsequent climate change
      developments in the province and makes suggestions as how best to pursue such a
      sustainability approach in British Columbia and other jurisdictions.

PMID- 16615693
TI  - Agriculture and deforestation in the tropics: a critical theoretical and
      empirical review.
AB  - Despite the important role that tropical forests play in human existence, their
      depletion, especially in the developing world, continue relentlessly. Agriculture
      has been cited as the major cause of this depletion. This paper discusses two
      main theoretical underpinnings for the role of agriculture in tropical
      deforestation. First, the forest biomass as input in agricultural production, and
      second, the competition between agriculture and forestry underlined by their
      relative marginal benefits. These are supported by empirical evidence from
      selected countries in Africa and South America. The paper suggests a need to find
      a win-win situation to control the spate of tropical deforestation. This may
      imply improved technologies in the agriculture sector in the developing world,
      which would lead both to increased production in the agriculture sector, and
      would also help control the use of tropical forest as an input in agriculture
      production.

PMID- 16615694
TI  - Recognizing local people's priorities for tropical forest biodiversity.
AB  - Tropical forest people often suffer from the same processes that threaten
      biodiversity. An improved knowledge of what is important to local people could
      improve decision making. This article examines the usefulness of explicitly
      asking what is important to local people. Our examples draw on biodiversity
      surveys in East Kalimantan (Indonesian Borneo). With local communities we
      characterized locally valued habitats, species, and sites, and their
      significance. This process clarified various priorities and threats, suggested
      refinements and limits to management options, and indicated issues requiring
      specific actions, further investigation, or both. It also shows how biological
      evaluations are more efficient with local guidance, and reveals potential for
      collaborations between local communities and those concerned with conservation.
      Such evaluations are a first step in facilitating the incorporation of local
      concerns into higher-level decision making. Conservationists who engage with
      local views can benefit from an expanded constituency, and from new opportunities
      for pursuing effective conservation.

PMID- 16615695
TI  - Small-scale co-management for the sustainable use of Xilingol biosphere reserve,
      inner Mongolia.
AB  - There exists a negative externality of livestock breeding due to the difference
      between private and social breeding cost in Xilingol Biosphere Reserve (XBR),
      Inner Mongolia, that has caused extensive ecological degradation of the
      grassland. The property rights regime, the household production responsibility
      system (HPRS), was adopted in the 1980s to increase livestock production in XBR.
      Although HPRS has successfully increased production by promoting private economic
      interests, it has led to grassland degradation due to inefficient enforcement of
      stock rate. Through interviews conducted with government representatives and
      herding families in all management units of XBR, we elucidate the shortfalls of
      the current management regime and the Fencing Grassland and Moving Users policy
      initiated in 2002 to restore grassland. We propose an alternative property rights
      regime, small-scale co-management, to concurrently promote both individual
      economic interests and grassland conservation by improving the enforcement of
      stock rate.

PMID- 16615696
TI  - Comment on the article "Fueling global fishing fleets" by Tyedmers, Watson and
      Pauly. Ambio 34(8) 635-638.

PMID- 16615697
TI  - Redundancy and response diversity of functional groups: implications for the
      resilience of coral reefs.
AB  - To improve coral reef management, a deeper understanding of biodiversity across
      scales in the context of functional groups is required. The focus of this paper
      is on the role of diversity within functional groups in securing important
      ecosystem processes that contribute to the resilience of coral-dominated reef
      states. Two important components of species biodiversity that confer ecosystem
      resilience are analyzed: redundancy and the diversity of responses within
      functional groups to change. Three critical functional groups are used to
      illustrate the interaction between these two components and their role in coral
      reef resilience: zooxanthellae (symbiotic micro algae in reef-building corals),
      reef-building corals, and herbivores. The paper further examines the consequences
      of undermining functional redundancy and response diversity and addresses
      strategies to secure ecological processes that are critical for coral reef
      resilience.

PMID- 16615698
TI  - Verification of the silica deficiency hypothesis based on biogeochemical trends
      in the aquatic continuum of Lake Biwa-Yodo River-Seto Inland Sea, Japan.
AB  - The silica deficiency hypothesis holds that increases of still waters caused by
      hydraulic alterations and high nitrogen (N) and phosphorus (P) discharges enhance
      the growth of freshwater diatoms, which take up the dissolved silicate (DSi)
      supplied by natural weathering. The consequent decrease in the DSi supply to the
      sea is advantageous to flagellates (nonsiliceous and potentially harmful) but not
      to diatoms (siliceous and mostly benign) in coastal marine ecosystems.
      Verification of this hypothesis has been hampered by lack of relevant data,
      particularly in Asia. We investigated the aquatic continuum composed of Lake
      Biwa, the Yodo River, and the Seto Inland Sea, Japan, where the natural
      conditions make the silica deficiency less likely to emerge due to the inherently
      rich supply of DSi. The results showed that the silica was retained both in the
      lake and nearby the estuary. The relative dominance of diatom and flagellates
      could not be explained solely by the stoichiometric arguments but by the
      supportive discussion on the difference of their behavioral characteristics and
      the process nearby the estuary, where direct inputs of N and P and effluent Si
      enhanced diatom bloom, even though the Si/N ratio was lowered in the upstream
      reservoir. Thus the retention of DSi occurred in two places: in the lake and
      nearby the estuary, where the other N and P are loaded directly. The rate of DSi
      retention correlated with socio-economic changes, such as rapid economic growth
      in the 1960s and mitigations implemented after the 1980s. Sensitivity of this
      continuum to the Si processes suggests the global significance of this
      hypothesis.

PMID- 16615701
TI  - Dialysis cruises.

PMID- 16615699
TI  - Willow (Salix fragilis Linn.): A multipurpose tree species under pest attack in
      the cold desert of Lahaul valley, northwestern Himalaya, India.
AB  - Salix fragilis is the most common willow species grown extensively under the
      indigenous agroforestry system in the cold desert of Lahaul valley located in the
      northwestern Himalayas, India. Presently, this tree is under severe pest attack,
      and other infections have made its survival in the area questionable. This
      deciduous multipurpose tree species provides vegetation cover to the barren
      landscape of Lahaul and is a significant contributor of fuel and fodder to the
      region. This study is a detailed profile of the plant in three villages within
      this region: Khoksar, Jahlma, and Hinsa. The willow provided 69.5%, 29%, and 42%
      of the total fuelwood requirements of Jahlma, Khoksar, and Hinsa respectively. A
      striking observation was that only 30.0 +/- 20.1% trees were healthy: 55.2 +/-
      16.1% of the willows have dried up and 14.8 +/- 6.1% were in drying condition due
      to a combination of pest infestation and infection. To sustain this cultivation
      of willow under the existing agroforestry system in the region, we recommend that
      locally available wild species and other established varieties of willow growing
      in similar regions of the Himalayas be introduced on a trial basis.

PMID- 16615702
TI  - Our peritonitis continuous quality improvement project: where there is a will
      there is a way.
AB  - Peritonitis was a significant problem for our peritoneal dialysis patients in
      2003. In January 2004, we initiated a continuous quality improvement project to
      address the problem. Our project took 18 months to complete. We developed many
      action items. Our first step was to analyze the data to ensure accuracy, and also
      to determine the causative organism that contributed most to the problem. The
      other steps we took included more education for the home dialysis nurses,
      creation of a home visit form, revisions to routine doctors' orders, revision of
      PD education tools, use of specialty materials for high-risk patients, one-time
      use for all drain equipment, change to peritonitis treatments and, lastly, group
      education for our patients. After taking all of these steps, there was no
      improvement to our peritonitis rates after a 12-month period. New action items
      were developed and included making changes to patient training and developing a
      home visit protocol. We also created a partnership with our local Community Care
      Access Centre and taught our community nurses how to help our patients with their
      peritoneal dialysis. It was after implementing these last changes that we noticed
      a significant improvement in our peritonitis rates. It was a lengthy and
      challenging process to go through but in the end, we are very pleased with our
      results. Not only has this improved the quality of our patients' lives, it has
      cut costs to our program, and has also helped us to expand our program
      significantly.

PMID- 16615703
TI  - Assessment of a fax document for transfer of medication information to family
      physicians and community pharmacists caring for hemodialysis outpatients.
AB  - BACKGROUND: Studies have clearly identified the outpatient dialysis population as
      one that is at high risk for drug-related problems. The objective of this study
      was to evaluate whether a fax document was useful for community pharmacies and
      family physicians to notify these health care providers that their patient was
      receiving hemodialysis, to update medication and allergy records, provide dosing
      information on antibiotics and drugs to avoid, facilitate communication from the
      hemodialysis unit, and to decide if this was a worthwhile project to continue on
      an on-going basis. METHODS: Fax documents were sent to community pharmacists and
      family physicians of 70 hemodialysis patients from two different hemodialysis
      satellite units. The fax document consisted of a brief cover letter with contact
      numbers, a copy of the patient's medication and allergy list, a table of
      appropriate antibiotic doses and medications to avoid in dialysis, and a survey
      to evaluate this project's usefulness. Fisher's exact test was used to determine
      whether there were any significant differences between the family physician and
      community pharmacist responses. RESULTS: The survey response rate was 37%. Ninety
      five per cent (20/21) of family physicians and 81% (22/27) of community
      pharmacists who responded to the survey would use the medication profile to
      update their records. Ninety-five per cent of family physicians and 93% of
      community pharmacies thought the fax document was an improvement in communication
      from the dialysis unit. Ninety per cent of family physicians and 85% of community
      pharmacies thought that the fax document was a worthwhile project for the
      dialysis unit to continue. No significant differences were found between family
      physician and community pharmacist responses. CONCLUSIONS: Implementation of a
      fax document for the transfer of medication information to family physicians and
      community pharmacists caring for hemodialysis patients aids in updating
      medication and allergy profiles, improves communication fom the dialysis unit and
      is considered a worthwhile project to continue on an ongoing basis.

PMID- 16615704
TI  - An update on the treatment and management of stroke.
AB  - There have been huge advancements in the prophylaxis and treatment of stroke. The
      majority of patients who have a stroke are asymptomatic prior to the event. This
      makes it extremely important to identify high-risk patients and administer
      prophylaxis where appropriate. However, risk factors, prophylaxis and treatment
      strategies are less clear in dialysis patients due to the lack of studies.
      Patients with chronic kidney disease have a higher risk of experiencing a stroke
      and dying from it. More studies need to be done in this area. For now, modifiable
      risk factors such as blood pressure and nutrition, should be promoted and
      prophylaxis and treatment administered with extra vigilance due to these
      patients' increased bleeding risk.

PMID- 16615705
TI  - Let's not call it custodial care.

PMID- 16615706
TI  - An interview with Dr. Laurie Gunter: a pioneer helping gerontological nurses
      establish educational roots. Interview by Ann Kolanowski.

PMID- 16615707
TI  - Legal issues in gerontological nursing--part 4: other significant issues.

PMID- 16615708
TI  - Nutrition in patients receiving home care in Finland: tackling the multifactorial
      problem.
AB  - This study describes the nutritional status of Finnish home care patients
      (n=178), their problems related to eating, digestion, and diet; their use of
      Meals on Wheels services; and informal caregivers' role in nutritional support.
      Half of the patients were at risk for malnutrition and 3% were malnourished
      according to Mini Nutritional Assessment (MNA) results. Most patients had
      problems with food intake, which were related to lower MNA scores. One-third of
      the participants had an unbalanced diet, and approximately half received
      assistance with shopping and food preparation from an informal caregiver. Home
      care patients' nutritional status, including all related aspects, such as
      shopping, food preparation, eating, and digestion, must be evaluated regularly
      and comprehensively.

PMID- 16615709
TI  - The Serial Trial Intervention: an innovative approach to meeting needs of
      individuals with dementia.
AB  - Individuals with dementia often use behaviors rather than specific verbal
      complaints to express the presence of a symptom or need. The Serial Trial
      Intervention uses systematic serial assessments and sequential trials of
      treatments to identify and treat unmet needs that may be the underlying cause of
      these behaviors. Because chronic pain is common and often under-treated in this
      population, a trial of analgesics is used when other approaches, including
      nonpharmacological treatments, have not been effective. A systematic approach to
      nursing assessment and treatment is needed to identify and treat discomfort and
      other unmet needs of individuals with dementia.

PMID- 16615710
TI  - Depression and gender differences: focus on Taiwanese American older adults.
AB  - Secondary analysis of cross-sectional data was used to examine gender differences
      and depression in elderly Taiwanese Americans. There is a paucity of health
      related research focused on Asian Americans. This is especially true in the area
      of mental health. Depression, the most common psychiatric illness in older
      adults, is under-diagnosed in Asian Americans. A convenience sample of 100
      elderly Taiwanese Americans, 47 women and 53 men, was used. Women were older, had
      higher depressions cores, more physical illness, poorer sleep scores, and less
      physical activity. Regression analysis indicated that 25% of the variance in
      depression scores was explained by sleep quality and physical activity.

PMID- 16615711
TI  - Stroke caregiving: difficult times, resource use, and needs during the first 2
      years.
AB  - Despite high levels of distress among stroke caregivers, research on resource use
      and unmet needs is limited. The major purposes of this study were to identify the
      most difficult times, unmet needs, and advice of caregivers during the first 2
      years of caregiving; and to examine resource use and perceptions of resource
      importance. Qualitative and quantitative methods were used. The hospitalization
      period and first months at home were most difficult for 76% of caregivers. Unmet
      needs were related to caregiver preparation, promoting the survivor's function,
      and sustaining the self and family. Although 50% or more of caregivers rated most
      resources important, only home health care was used by 50% of caregivers.
      Findings can aid clinicians in educating and counseling caregivers to reduce
      distress.

PMID- 16615712
TI  - Assessing cognitive ability in research: use of MMSE with minority populations
      and elderly adults with low education levels.
AB  - The Mini-Mental State Examination (MMSE), originally designed to screen for
      dementia, is an instrument currently used extensively to assess cognitive status
      in clinical and community settings. This descriptive study compares standard MMSE
      scores to MMSE scores adjusted for age and education in a sample of 414 elderly
      Black and White women living independently in communities. After scores were
      adjusted, 14 participants (all Black) were moved from categories of mild
      cognitive impairment to unimpaired cognitive ability. However, even after scores
      were adjusted for age and education, White elderly adults still had higher mean
      scores than Black elderly adults (p = .003), suggesting that racial differences
      may have an effect on MMSE performance independent of age and education. Further
      research is needed to better understand the interaction of race and culture on
      MMSE outcomes. Implications are offered for appropriate use of the MMSE
      considering factors of age, education, and racial differences to guide evidence
      based practice by gerontological nurses engaged in work with elderly populations.

PMID- 16615713
TI  - An editorial on maintaining the outreach of Canadian psychology through the study
      of the brain, behaviour, and cognitive science.

PMID- 16615714
TI  - [Conceptual structures, representation of objects and object relations].
AB  - This article provides an overview of psychological studies of object concepts,
      highlighting the more recent re-conceptualizations, and the latest developments
      in research in this field. These developments have tended to focus on the notion
      of context, as well as on the notion of causal relations between features. Our
      theoretical analysis of this field is backed up by experimental illustrations. We
      complete with an examination of "category-specific impairments" studies, in the
      light of the evolution of concept theories.

PMID- 16615715
TI  - Is there "feedback" during visual imagery? Evidence from a specificity of
      practice paradigm.
AB  - The specificity of practice hypothesis predicts the development of a sensorimotor
      representation specific to the afferent feedback available during skill
      acquisition (Proteau, 1992; Proteau, Marteniuk, Girouard, & Dugas, 1987). In the
      present investigation, we used the specificity of practice hypothesis to test
      whether skill acquisition through visual imagery would lead to the development of
      a sensory-specific movement representation similar to one resulting from actual
      practice. To accomplish this objective, participants practiced walking a 12-m
      linear path in one of three practice conditions, full-vision (FV), no-vision
      (NV), or visual imagery (VI), for either 10 or 100 trials. Knowledge of spatial
      and/or temporal results (KR) was provided to participants following each trial
      during this phase. Following acquisition, participants completed 10 NV trials
      without KR. An analysis of root-mean-squared-error (RMSE) indicated NV
      participants were more accurate than both FV and VI participants in the transfer
      condition. We believe the equivalence in transfer RMSE between FV and VI suggests
      that there are similarities between the movement representations attained by FV
      and VI practice.

PMID- 16615716
TI  - Recognizing National Hockey League greatness with an ignorance-based heuristic.
AB  - This study examined whether people adhered to the recognition heuristic (i.e.,
      inferred that a recognized hockey player had more total career points than an
      unrecognized player) and whether using this heuristic could yield accurate
      decisions. On paired comparisons, having participants report whether they
      recognized each player plus any knowledge they had about each player permitted
      players to be classified as either unrecognized (UR), merely recognized (MR), or
      recognized with additional knowledge (RK), thus producing six possible trial
      types. Participants adhered to the recognition heuristic on 95% of MR-UR trials
      and were accurate on 81% of those trials. They chose the recognized player on 98%
      of RK-UR trials, yielding 94% accuracy. Women had less knowledge and recognized
      fewer players than men, yet they were nearly as accurate as men. Future research
      should examine the conditions under which the recognition heuristic is an
      adaptive strategy.

PMID- 16615717
TI  - Conformity in a generative linguistic task: the role of category and strategic
      nonword use.
AB  - Marsh, Ward, and Landau (1999) demonstrated that participants asked to create
      novel words use elements of sample nonwords they are given, even when instructed
      to avoid use of the examples. In four studies, we replicated the effect of
      conformity to sample nonwords and found the effect was not influenced by the
      semantic category of the words unless those words shared orthographic
      characteristics. We found that although we could increase conformity to examples
      when word exemplars were grouped by category, it was likely that much of this
      increase was strategically driven. We propose that the presence of the sample non
      words, presented in groups with the same word rules, created an orthographic
      category used by participants in the word creation task.

PMID- 16615718
TI  - Is the Chinese number-naming system transparent? Evidence from Chinese-English
      bilingual children.
AB  - Chinese-speaking children have been shown to have an advantage over English
      speaking children in a variety of mathematical areas, including counting. One
      possible explanation for the advantage in counting is that the Chinese number
      naming system is relatively transparent, compared to English, in that number
      names typically are directly indicative of base-10 structure (e.g., 12 is named
      "ten-two" rather than "twelve"). To determine whether the transparency of the
      Chinese number-naming system influences counting in bilingual children, we tested
      25 Chinese-English bilingual children between the ages of 3 and 5 years, both in
      English and in Chinese. Children were asked to count as high as they could
      (abstract counting) and also to count objects in small, medium, and large arrays
      (object counting). No evidence was found for transparency or for transfer from
      one language to the other. Instead, relative proficiency in the two languages
      influenced counting skill. These results are discussed in terms of linguistic and
      cultural variables that might account for cross-linguistic differences in
      counting.

PMID- 16615719
TI  - Effect of bilingualism and computer video game experience on the Simon task.
AB  - A group of 97 participants who were monolingual or bilingual and who had
      extensive practice playing computer video games or not completed two Simon tasks.
      The tasks were presented in two conditions that manipulated the number of
      response switches required in each block of trials. Bilingualism and video-game
      experience each influenced a different aspect of performance: Video-game players
      were faster in most conditions, including control conditions that did not include
      conflict from irrelevant position; bilinguals were faster only in a condition
      that required the most controlled attention to resolve conflict from the position
      and the stimulus. The results show the potential of experience to modify
      performance and point to subtle processing differences in various versions of the
      Simon task.

PMID- 16615720
TI  - Recollections of an accidental contrarian.

PMID- 16615721
TI  - [The future of sexology].

PMID- 16615722
TI  - [Erectile dysfunction: a potential useful marker for cardiovascular disease].
AB  - Erectile dysfunction is defined as the inability to achieve and/or maintain an
      erection sufficient to permit satisfactory sexual intercourse. Most cases of
      erectile dysfunction have a vascular etiology and, in patients with known
      cardiovascular disease, the degree of erectile dysfunction correlates with
      severity of that disease. In addition, cardiovascular disease and erectile
      dysfunction share the same risk factors for atherosclerosis and have a common
      pathophysiology (endothelial dysfunction); thus, erectile dysfunction appears as
      an early and sentinel symptom in patients with occult vascular disease, of the
      coronary or carotid arteries.

PMID- 16615723
TI  - [Sexual problems after allogenic stem cell transplantation].
AB  - Allogenic stem cell transplantation is an effective procedure for malignant
      haematological diseases, for these reasons the number of long-term survivors has
      increased as well as the concern for their quality of life. The late effects of
      transplantation can highly influence the patient's sexuality and relationships
      through psychological and physical factors. Psychological factors: regression due
      to sickness, staff-dependency, emotional and physical partner-dependence,
      distress related to sterility. Physical factors: hypo-oestrogenism, genital
      mucosae dryness and sometimes vulval or vaginal chronic graft-versus-host
      disease. Addressing the topic of intimacy may cause anxiety and embarrassment
      among nurses, haematological staff and practitioners with the risk of leaving
      patients in a sort of "conspiracy of silences".

PMID- 16615724
TI  - [The neurophysiology of the female orgasm].
AB  - The way women experience orgasm during passionate sexual activity has been of
      interest throughout the ages. The astonishing advances of functional imaging
      techniques recently allowed unravelling the neuroanatomy of female orgasm within
      a distributed corticosubcortical neural network. In the present article, we
      review the clinical and experimental evidence that attributes orgasm not only a
      peripheral but also a central origin. We thus outline the importance of
      integrating orgasm as a complex process involving the entire woman, mind and
      body. In light of this, future studies in female sexuality would need to take
      account of the consequences of both standard approaches in sexology and
      functional imaging results in the understanding of the human sexual function and
      in the treatment of sexual dysfunctions.

PMID- 16615725
TI  - [Sleep and sexuality].
AB  - Our knowledge about the multiple aspects of sleep functions are still
      insufficient. Concerning the relationship between sleep and sexuality there are
      four points of view to take into account. Two observations: a spontaneous sexual
      excitement during REM sleep and that some anxious dreams can produce also sexual
      arousal. Two hypotheses: the erotic pleasure could be easier to perceive in a
      sleeping or dreaming state than in a waking state and some sleeping troubles
      could have an important influence on the sexual life of a couple.

PMID- 16615726
TI  - [Adolescence and sexuality].
AB  - Different pathological states occurring during adolescence, such as anorexia,
      bulimia and suicidal attempts are seen as possible manifestations of
      psychological defence mechanisms against the anxiety-provoking bodily changes of
      puberty and the necessary psychological transformations inherent to adolescence
      and sexual maturation. The changes of object of desire and some sexual risk
      behaviours are illustrated by clinical vignettes. Music is suggested to play a
      role in the mobilisation of emotions, bodily sensations and in the construction
      of an imaginary world and thus to be a factor--a part from biological and psycho
      social ones--influencing the sexual behaviour of adolescents. Some communication
      techniques are suggested enabling access to adolescents on sexual matters - a
      domain of increasing public health importance.

PMID- 16615727
TI  - [Investigation of sexual disorders].
AB  - It is not easy for physicians to investigate genuinely sexual problems because of
      our personal conceptions about sex related to our familial and religious
      upbringing. Lack of medical education or information and bad personal experiences
      inhibit us from speaking freely with our patients. And they, before daring to
      talk to us about a sexual problem, must already be suffering from severely
      handicapped relations. Being able to explore in details what causes them problem,
      to investigate if there is a real sexual dysfunction and how it occurs, will help
      patients a great deal by providing them a precise diagnosis. We must therefore
      determine whether the sexual problem is the symptom of a somatic or a psychiatric
      disease, or a secondary effect of a medication or a drug, before identifying it
      as a psychosomatic or emotional dysfunction.

PMID- 16615728
TI  - [Questions in Ent].
AB  - Role of Helicobacter Pylori and nasopharyngeal bacteries in the pathogenesis of
      otitis media. Interest of Tonsillectomy in MRSA positive patients. Sleep apnea
      syndrome increases sudden death during night. Prevalence of Acoustic Neuroma, and
      surgical difficulties in case of conservative treatment failures. Role of CRP in
      the sinus treatment's decision. Is sinusitis influenced by anatomical factors? Do
      we have to treat with antibiotics? Role of mycosis? Are the sprays for snorers
      efficient? Is the facial nerve now radiologically visible? Are systematic
      punctures of thyroid nodules mandatory and with what frequency? Cetuximab is a
      promessing treatment in ENT.

PMID- 16615729
TI  - [Bradycardia in an elderly woman caused by amiodarone assessed by ECG].

PMID- 16615731
TI  - [Forced tube feeding of Guantanamo Bay hunger strikes].

PMID- 16615732
TI  - [Can antidepressants be reasonably prescribed for children?].

PMID- 16615733
TI  - [Passing the mark of the first 100 deaths].

PMID- 16615734
TI  - [The government and organ transplantation].

PMID- 16615735
TI  - New approaches to a timeless dilemma.

PMID- 16615736
TI  - Plain talk about wound pain.

PMID- 16615737
TI  - The law on failure to treat pain.

PMID- 16615738
TI  - Chronic wound pain and palliative cancer care.

PMID- 16615739
TI  - Dressing the discomfort: managing radiation therapy-induced dermatitis.

PMID- 16615740
TI  - Lymphedema: skin and wound care in an aging population.

PMID- 16615741
TI  - Making the case for using a silicone dressing in burn wound management.

PMID- 16615742
TI  - Treating venous insufficiency ulcers with soft silicone dressing.

PMID- 16615743
TI  - Silicone net dressing as an adjunct with negative pressure wound therapy.

PMID- 16615744
TI  - Considering patient priorities when choosing a dressing.

PMID- 16615745
TI  - Language performance of low-income African American and European American
      preschool children on the PPVT-III.
AB  - PURPOSE: The performance of low-income African American preschoolers (36 to 52
      months old) on the Peabody Picture Vocabulary Test--Third Edition (PPVT-III; L.
      M. Dunn & L. M. Dunn, 1997) was examined to provide a norm for assessing the
      performance of this population and to explore the link between socioeconomic
      status (SES) and language scores on the PPVT-III. METHOD: Four hundred and eighty
      two African American and 52 European American children in a comparison group were
      individually administered the PPVT-III. RESULTS: On average, African American
      children performed approximately 1.5 SD below the expected mean based on national
      norms. Using standard cutoff scores, the PPVT-III identified more children as
      having language delays than did other measures of language abilities.
      Socioeconomic factors were related to PPVT-III scores, indicating that the degree
      of disadvantage within children with low SES was related to language abilities.
      Maternal education level, marital status, and the number of children in the
      household were uniquely associated with children's performance on the PPVT-III.
      CLINICAL IMPLICATIONS: The importance of supporting language development in
      preschool children from low-income families is discussed.

PMID- 16615746
TI  - Performance on the PPVT-III and the EVT: applicability of the measures with
      African American and European American preschool children.
AB  - PURPOSE: The purpose of this study was to determine whether two vocabulary
      measures were appropriate for the evaluation of African American children and
      children whose mothers have low education levels, regardless of gender. METHOD:
      Data were collected for 210 high-risk, preschool children from a southeastern
      state in the United States on the Peabody Picture Vocabulary Test--Third Edition
      (PPVT-III; L. M. Dunn & L.M. Dunn, 1997) and the Expressive Vocabulary Test (EVT;
      K. T. Williams, 1997). RESULTS: Results indicated that African American children
      and children whose mothers had low education levels tended to score lower on both
      measures than did children from European American backgrounds and children whose
      mothers had a high school or higher education; however, this effect was larger
      for the PPVT-III. CLINICAL IMPLICATIONS: Data suggest that the EVT is a better
      indicator of a child's "vocabulary" skill, and that the PPVT-III has a greater
      tendency than the EVT to place African American children and children whose
      mothers have low education levels at risk for being unfairly identified as
      presenting with a potential language disorder. These data indicate that
      practitioners should use alternative assessment methods such as nonstandard and
      dynamic assessments to test children's vocabulary skill. In particular, if they
      use the PPVT-III, practitioners should take great caution in interpreting test
      results as evidence of a vocabulary problem in African American children and
      children whose mothers have low education levels.

PMID- 16615747
TI  - English language narratives of Filipino children.
AB  - PURPOSE: The current study focuses on describing the English language narrative
      skills of children who have been exposed to the Filipino language. METHOD: Eight
      children between the ages of 6;0 (years;months) and 7;7 who spoke primarily
      English but who were exposed to the Filipino language at home participated. Each
      child produced three narrative samples based on wordless picture books. Samples
      were analyzed for narrative complexity as well as measures of productivity and
      grammaticality. RESULTS: The complexity of children's narratives was comparable
      to that reported in the literature for monolingual English-speaking children.
      Grammaticality measures show use of an average of 16.55% Filipino-influenced
      English forms across three stories. The observed patterns of Filipino-influenced
      English were predictable based on the comparison of English and Filipino
      structures. Variability in maze use was related to the amount of exposure to
      Filipino. CLINICAL IMPLICATIONS: Care should be taken to evaluate grammaticality
      with respect to nonstandard English forms predicted by the rules of the language
      in contact with English. Further, maze use may be related to level of exposure to
      another language and should be further explored when using such information in
      language evaluation.

PMID- 16615748
TI  - Coach talk: linguistic demands inherent in youth sports.
AB  - PURPOSE: This investigation expands the notion of academic language to
      extracurricular activities and provides preliminary data regarding linguistic
      expectations that are place on students who are participating in youth sports.
      METHOD: Five coaches of young girls' basketball teams (2 competitive; 3
      recreational) were observed during practice sessions divided into individual
      versus group and stationary versus active contexts. Communication was
      characterized with various measures of content, form, and use. RESULTS: Coaches
      rarely used pauses or communicative repetitions. Recreational coaches' utterances
      contained more mazes than competitive coaches' utterances. Utterances used during
      stationary activities tended to be longer and contain more than one verb compared
      to utterances used during active activities; sentence fragments were more
      frequent during active contexts. All coaches used jargon quite frequently.
      CLINICAL IMPLICATIONS: The system reported here can be used to document
      linguistic demands in other extracurricular activities, such as music programs
      and scouting. Speech-language pathologists might include clinical activities to
      help students deal successfully with the linguistic requirements that are
      inherent in sporting activities.

PMID- 16615749
TI  - Family members' perceptions of augmentative and alternative communication device
      use.
AB  - PURPOSE: Although advancements in technology have expanded the use of
      augmentative and alternative communication (AAC) devices for children with
      disabilities, the use of AAC devices in school and home settings is often
      inconsistent. The purpose of this study was to examine family members'
      perceptions regarding the use of AAC devices. Factors that were perceived to
      affect student's use of AAC devices, family expectations, and benefits of AAC
      device use were explored. METHOD: Semistructured interviews were conducted with 6
      family members (primary caregivers) of 7 youth who primarily use AAC devices to
      communicate in the school environment. The interviews were analyzed using cross
      case analysis. RESULTS: A variety of common perspectives emerged from the data,
      including four thematic categories: expectations, facilitators, barriers, and
      benefits of AAC device use. IMPLICATIONS: Information gained in this
      investigation may be used to improve professional-family and teaming
      relationships and serve to benefit AAC users in school and home settings.

PMID- 16615750
TI  - Eligibility criteria for language impairment: is the low end of normal always
      appropriate?
AB  - PURPOSE: The assumption that children with language impairment will receive low
      scores on standardized tests, and therefore that low scores will accurately
      identify these children, is examined through a review of data in the manuals of
      tests that are intended for use in identifying such children. METHOD: Data from
      43 commercially available tests of child language were compiled to identify
      whether evidence exists to support their use in identifying language impairment
      in children. RESULTS: A review of data concerning the performance of children
      with impaired language failed to support the assumption that these children will
      routinely score at the low end of a test's normative distribution. A majority of
      tests reported that such children scored above 1.5 SD below the mean, and scores
      were within 1 SD of the mean for more than a quarter (27%) of the tests. The
      primary evidence needed to support the purpose of identification, test
      sensitivity and specificity, was available for 9 of the 43 tests, and acceptable
      accuracy (80% or better) was reported for 5 of these tests. IMPLICATIONS:
      Specific data supporting the application of "low score" criteria for the
      identification of language impairment is not supported by the majority of current
      commercially available tests. However, alternate sources of data (sensitivity and
      specificity rates) that support accurate identification are available for a
      subset of the available tests.

PMID- 16615751
TI  - From an evidence-based practice and treatment efficacy research viewpoint:
      comments about the clinical forum on "What Child Language Research May Contribute
      to the Understanding and Treatment of Stuttering".

PMID- 16615752
TI  - Relative sensitivity factors of inorganic cations in frozen-hydrated standards in
      secondary ion MS analysis.
AB  - We describe the measurement, at 100 K, of the SIMS relative sensitivity factors
      (RSFs) of the main physiological cations Na+, K+, Mg2+, and Ca2+ in frozen
      hydrated (F-H) ionic solutions. Freezing was performed by either plunge freezing
      or high-pressure freezing. We also report the measurement of the RSFs in flax
      fibers, which are a model for ions in the plant cell wall, and in F-H ionic
      samples, which are a model for ions in the vacuole. RSFs were determined under
      bombardment with neutral oxygen (FAB) for both the fibers and the F-H samples. We
      show that referencing to ice-characteristic secondary ions is of little value in
      determining RSFs and that referencing to K is preferable. The RSFs of Na relative
      to K and of Ca relative to Mg in F-H samples are similar to their respective
      values in fiber samples, whereas the RSFs of both Ca and Mg relative to K are
      lower in fibers than in F-H samples. Our data show that the physical factors
      important for the determination of the RSFs are not the same in F-H samples and
      in homogeneous matrixes. Our data show that it is possible to perform a SIMS
      relative quantification of the cations in frozen-hydrated samples with an
      accuracy on the order of 15%. Referencing to K permits the quantification of the
      ionic ratios, even when the absolute concentration of the referencing ion is
      unknown. This is essential for physiological studies of F-H biological samples.

PMID- 16615753
TI  - Polychromatic microarrays: simultaneous multicolor array hybridization of eight
      samples.
AB  - High-throughput microscale platforms have transformed modern analytical
      investigations. Traditional microarray analyses involve a comparative approach,
      with two samples, a known control and an unknown sample, hybridized side-by-side
      and then contrasted for genetic differences. The samples are labeled with
      separate dyes and hybridized together, providing a differential expression
      pattern based on the reporter intensities. In contrast, the fiber-optic
      microarray platform described herein is analyzed with a microscope, thereby
      enabling the use of virtually any reporter, including quantum dots. The
      instrumentation takes advantage of the narrow emission bands characteristic of
      quantum dots to perform multiplexed detection of Bacillus anthracis. Advancing
      beyond the standard red/green microarray experiment, a panel of eight reporters
      were linked to eight B. anthracis samples and simultaneously analyzed in a
      microarray format. The ability to employ an assortment of reporters, along with
      the capacity to simultaneously hybridize eight samples confers an unprecedented
      flexibility to array-based analyses, providing a 4-fold increase in throughput
      over standard two-color assays.

PMID- 16615754
TI  - Polarization modulation-infrared reflection absorption spectroscopic mapping.
AB  - Polarization modulation-infrared reflection absorption spectroscopy (PM-IRRAS)
      has been coupled with a stepwise mapping of the sample in order to characterize
      the molecular orientation across the surface. An optical setup has been developed
      to facilitate the PM-IRRAS mapping. With PM-IRRAS mapping used in conjunction
      with a common FT-IR spectrometer, the achievable lateral resolution of
      approximately 45 mum is energy-limited rather than diffraction-limited. PM-IRRAS
      mapping was used to study the molecular orientation of octadecanephosphonic acid
      (OPA) molecules attached on a microstructured aluminum oxide/gold surface. The
      spectroscopic map reveals that OPA is preferably spotty attached on the aluminum
      oxide surface. The attached molecules form a highly ordered film. A lower degree
      of ordering was found for phosphonic acid adsorbed on gold mainly in a tridentate
      bonding mode. Results demonstrate that PM-IRRAS mapping has a considerable
      potential for revealing inhomogenities within ultrathin films attached on a
      surface.

PMID- 16615755
TI  - Sequential flow injection analysis system on-line coupled to high intensity
      focused ultrasound: green methodology for trace analysis applications as
      demonstrated for the determination of inorganic and total mercury in waters and
      urine by cold vapor atomic absorption spectrometry.
AB  - A new concept is presented for green analytical applications based on coupling on
      line high-intensity focused ultrasound (HIFU) with a sequential injection/flow
      injection analysis (SIA/FIA) system. The potential of the SIA/HIFU/FIA scheme is
      demonstrated by taking mercury as a model analyte. Using inorganic mercury,
      methylmercury, phenylmercury, and diphenylmercury, the usefulness of the proposed
      methodology for the determination of inorganic and total mercury in waters and
      urine was demonstrated. The procedure requires low sample volumes and reagents
      and can be further applied to all chemical reactions involving HIFU. The inherent
      advantages of SIA, FIA, and HIFU applications in terms of high throughput,
      automation, low reagent consumption, and green chemistry are accomplished
      together for the first time in the present work.

PMID- 16615756
TI  - Mid-IR biosensor: detection and fingerprinting of pathogens on gold island
      functionalized chalcogenide films.
AB  - Antibody (human IgG, anti-E. coli O157:H7, and anti-Salmonella) complexes on the
      surface of IR-transparent Ge-containing chalcogenide glass films were formed via
      thiol chemistry on 20-nm-thick gold islands. As a first step, the protocol was
      validated by monitoring fluorescently tagged targets to validate binding. FT-IR
      spectroscopy confirmed that the coating of the films with 20-nm gold did not have
      a significant effect on the propagation and penetration of IR evanescent waves
      through the film. The films functionalized with anti-E. coli O157:H7 and anti
      Salmonella antibodies were used to detect E. coli O157:H7 and S. enteriditis
      through label-free IR fingerprinting. Highly selective detection of bacterial
      targets was achieved at both the species (E. coli vs. S. enteriditis) and strain
      level (E. coli O157:H7 vs E. coli K12). A mid-infrared approach could thus be
      used as a biosensor as well as a molecular fingerprinting tool.

PMID- 16615758
TI  - Enzyme inhibitor screening by capillary electrophoresis with an on-column
      immobilized enzyme microreactor created by an ionic binding technique.
AB  - A novel strategy for screening the enzyme inhibitors from the complex mixtures by
      capillary electrophoresis with an on-column immobilized enzyme microreactor
      created by an ionic binding technique is reported. The enzyme microreactor was
      prepared in two steps: First, the capillary wall was dynamically coated with a
      polycationic electrolyte hexadimethrine bromide (HDB) by simply flushing the
      column using the HDB solution. Subsequently, a plug of the enzyme solution was
      injected and incubated for 5 min to permit the enzyme molecules to immobilize on
      the positively charged coating via ionic binding. To demonstrate this strategy,
      angiotensin-converting enzyme (ACE) was employed as a model for the enzyme
      immobilization, inhibition study, and inhibitor screening. It has been proved
      that such a prepared immobilized ACE microreactor displays a high enough activity
      and stability. Furthermore, the immobilized enzyme microreactor could be easily
      renewed. The inhibition study or inhibitor screening was accomplished through the
      following procedure: (i) the substrate solution was injected and incubated within
      the microreactor for a short time span; (ii) subsequently, the voltage was
      applied to separate the product of the enzyme reaction from the unreacted
      substrate based on their different mobilities, the peak area of the product
      representing the enzyme activity; (iii) a certain amount of enzyme inhibitor or
      candidate compound was spiked into the substrate solution to assay the reduction
      of the immobilized enzyme activity. Thus, the inhibitors can be easily identified
      if the reduced peak area of the product is observed in electropherograms. Because
      the injection volume of the capillary was only 9.8 nL and the enzyme could be
      reusable, the assay cost could be dramatically reduced. The screening of a small
      compound library containing natural extracts and commercially available
      inhibitors was performed. The present approach has proved to be simple, rapid,
      and robust.

PMID- 16615757
TI  - Electrochemical multianalyte immunoassays using an array-based sensor.
AB  - A novel amperometric biosensor for performing simultaneous electrochemical
      multianalyte immunoassays is described. The sensor consisted of eight iridium
      oxide sensing electrodes (0.78 mm(2) each), an iridium counter electrode, and a
      Ag/AgCl reference electrode patterned on a glass substrate. Four different
      capture antibodies were immobilized on the sensing electrodes via adsorption.
      Quantification of proteins was achieved using an ELISA in which the
      electrochemical oxidation of enzyme-generated hydroquinone was measured. The
      spatial separation of the electrodes enabled simultaneous electrochemical
      immunoassays for multiple proteins to be conducted in a single assay without
      amperometric cross-talk between the electrodes. The simultaneous detection of
      goat IgG, mouse IgG, human IgG, and chicken IgY was demonstrated. The detection
      limit was 3 ng/mL for all analytes. The sensor had excellent precision (1.9-8.2%
      interassay CV) and was comparable in performance to commercial single-analyte
      ELISAs. We anticipate that chip-based sensors, as described herein, will be
      suitable for the mass production of economical, miniaturized, multianalyte assay
      devices.

PMID- 16615759
TI  - On-chip amperometric measurement of quantal catecholamine release using
      transparent indium tin oxide electrodes.
AB  - Carbon-fiber amperometry has been extensively used to monitor the time course of
      catecholamine release from cells as individual secretory granules discharge their
      contents during the process of quantal exocytosis, but microfabricated devices
      offer the promise of higher throughput. Here we report development of a microchip
      device that uses transparent indium tin oxide (ITO) electrodes to measure quantal
      exocytosis from cells in microfluidic channels. ITO films on a glass substrate
      were patterned as 20-mum-wide stripes using photolithography and wet etching and
      then coated with polylysine to facilitate cell adherence. Microfluidic channels
      (100 mum wide by 100 mum deep) were formed by molding poly(dimethylsiloxane)
      (PDMS) on photoresist and then reversibly sealing the PDMS slab to the ITO-glass
      substrate. Bovine adrenal chromaffin cells were loaded into the microfluidic
      channel and adhered to the ITO electrodes. Cells were stimulated to secrete by
      perfusing a depolarizing "high-K" solution while monitoring oxidation of
      catecholamines on the ITO electrode beneath the cell using amperometry.
      Amperometric spikes with charges ranging from 0.1 to 1.5 pC were recorded with a
      signal-to-noise ratio comparable to that of carbon-fiber electrodes. Further
      development of this approach will enable high-throughput measurement of quantal
      catecholamine release simultaneously with optical cell measurements such as
      fluorescence.

PMID- 16615760
TI  - Label-free microelectronic PCR quantification.
AB  - We present a robust and simple method for direct, label-free PCR product
      quantification using an integrated microelectronic sensor. The field-effect
      sensor can sequentially detect the intrinsic charge of multiple unprocessed PCR
      products and does not require sample processing or additional reagents in the PCR
      mixture. The sensor measures nucleic acid concentration in the PCR relevant range
      and specifically detects the PCR products over reagents such as Taq polymerase
      and nucleotide monomers. The sensor can monitor the product concentration at
      various stages of PCR and can generate a readout that resembles that of a real
      time fluorescent measurement using an intercalating dye but without its potential
      inhibition artifacts. The device is mass-produced using standard semiconductor
      processes, can be reused for months, and integrates all sensing components
      directly on-chip. As such, our approach establishes a foundation for the direct
      integration of PCR-based in vitro biotechnologies with microelectronics.

PMID- 16615761
TI  - Overload for ionized solutes in reversed-phase high-performance liquid
      chromatography.
AB  - Overloading occurs for submicrogram quantities of ionized solutes particularly
      when using low ionic strength mobile phases at low pH (e.g., formic acid), even
      with highly inert silica RP-HPLC columns of normal dimensions. Much higher loads
      can produce a sharp L-shaped peak with retention above the column void volume, in
      line with the hypothesis that a small number of high-energy sites fill first and
      are rapidly overloaded, followed by a much larger number of weaker sites.
      However, charged acids and bases show identical overloading behavior; overloading
      is reduced as the mobile-phase ionic strength is increased. These findings raise
      questions about the physical nature of the strong sites. The rapid overloading of
      silica and purely polymeric phases could be explained by mutual repulsion of
      ionic species or their inability to fully penetrate the hydrophobic structure of
      the phase. However, these alternative hypotheses cannot readily explain the high
      total saturation capacities obtained using frontal analysis. Ion pairing with
      trifluoroacetic acid may reduce overload, while the effect is less important for
      formate or phosphate buffers. A surface layer of acetonitrile is not a
      prerequisite for rapid overloading, as shown by studies using purely aqueous
      buffers.

PMID- 16615762
TI  - Examination of the spatially heterogeneous electroactivity of boron-doped diamond
      microarray electrodes.
AB  - Spatial variations in the electrical and electrochemical activity of microarray
      electrodes, fabricated entirely from diamond, have been investigated. The arrays
      contain approximately 50-mum-diameter boron-doped diamond (BDD) disks spaced 250
      mum apart (center to center) in insulating intrinsic diamond supports, such that
      the BDD regions are coplanar with the intrinsic diamond. Atomic force microscopy
      (AFM) imaging of the surface reveals a roughness of no more than +/-10 nm over
      the array. Each BDD microdisk within the array contains polycrystalline BDD with
      a variety of different grains exposed. Using conducting-AFM, the conductivity of
      the different grains was found to vary within a BDD microdisk. Electrochemical
      imaging of the electroactivity of the microdisk electrodes using scanning
      electrochemical microscopy operating in substrate generation-tip collection mode
      revealed that, under apparently diffusion-limited steady-state conditions, there
      was a small variation in the response between electrodes. However, the majority
      of electrodes in the array appeared to show predominantly metallic behavior. For
      the electrodes that showed a lower activity, all grains within the microdisk
      supported electron transfer, albeit at different rates, as evidenced by studies
      on the electrodeposition of metallic silver, at potentials far negative of the
      flat band potential of oxygen-terminated polycrystalline diamond. The possibility
      of using these array electrodes for steady-state diffusion-limited measurements
      in electroanalytical applications is far-reaching. However, caution should be
      exercised in the kinetic analysis of voltammetric measurements, since wide
      variations in the electroactivity of individual grains are apparent when the
      potential is below the diffusion-limited value.

PMID- 16615763
TI  - Grafting of poly(ethylene glycol) onto poly(acrylic acid)-coated glass for a
      protein-resistant surface.
AB  - The surface of solid glass supports for samples in optical microscopy and for
      biosensors needs to be protein-resistant. A coating of a poly(ethylene glycol)
      monomethyl ether (mPEG) on the surface of the glass is one promising method for
      preventing the nonspecific adsorption of proteins. In this study, we have
      developed a novel technique for achieving an optimal coverage of a glass surface
      with mPEG to prevent protein adhesion. A clean glass substrate previously treated
      with (3-aminopropyl)dimethylethoxysilane (APDMES) was treated sequentially with
      poly(acrylic acid) and subsequently a primary amine derivative of mPEG in the
      presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The resultant glass
      surface was demonstrated to be highly protein-resistant, and the adsorption of
      bovine serum albumin decreased to only a few percentage points of that on a glass
      surface treated with APDMES alone. Furthermore, to extend the present method, we
      also prepared a glass substrate on which biotinylated poly(ethylene glycol) was
      cografted with mPEG, and biotinylated myosin subfragment-1 (biotin-S1) was
      subsequently immobilized on this substrate by biotin/avidin chemistry. Actin
      filaments were observed to glide on the biotin-S1-coated glass surface in the
      presence of ATP, and thus, the method is capable of immobilizing the protein
      specifically without any loss in its biological function.

PMID- 16615764
TI  - Effect of carrier ionic strength in microscale cyclical electrical field-flow
      fractionation.
AB  - Recent work with cyclical electrical field-flow fractionation systems has shown
      promise for the technique as a separation and analysis tool, but little is
      understood about how the carrier composition in the system affects its
      capabilities. The electrical properties of microscale CyElFFF systems change when
      the carrier ionic conditions are altered, and it is well known that the effects
      of increasing ionic strength carriers on retention in normal ElFFF systems are
      severe. Specifically, retention levels fall significantly. Accordingly, this work
      seeks to understand the effect that increasing carrier ionic strength in CyElFFF
      has on nanoparticle retention in the channels. The retention of polystyrene
      particles in the CyElFFF microsystem is reported at various ionic strengths of
      ammonium carbonate and at a variety of pH levels. The experiments are compared to
      the theory of CyElFFF available in the literature. The results indicate that the
      ionic strength of the carrier has a significant impact on retention and that high
      ionic strength carrier solutions lead to poor performance of the CyElFFF system.
      These results have significant impact on the possible uses of the technique and
      its applications, especially in the biomedical arena.

PMID- 16615765
TI  - Phase-changing sacrificial materials for interfacing microfluidics with ion
      permeable membranes to create on-chip preconcentrators and electric field
      gradient focusing microchips.
AB  - We have developed a novel approach for interfacing ionically conductive membranes
      with microfluidic systems using phase-changing sacrificial layers. Imprinted
      microchannels in a polymer substrate are filled with a heated liquid that
      solidifies at room temperature, a monomer solution is placed over the protected
      channels and polymerized to form a rigid semipermeable copolymer, and then the
      protective layer is melted and removed, leaving an open microchannel interfaced
      with a polymer membrane. We have applied this method in miniaturizing electric
      field gradient focusing (EFGF) and carrying out on-chip protein preconcentration.
      A semipermeable copolymer in the EFGF microchips fills a region of changing cross
      sectional area, which allows a gradient in electric field to be established when
      an electrical potential is applied. Our technique provides microchip EFGF devices
      that offer 3-fold improved resolution in protein focusing compared with capillary
      based systems. In addition, these EFGF microchips can separate peptide samples
      with resolution similar to what is obtained in capillary electrophoresis
      microdevices, and the micro-EFGF systems enrich analytes by a factor of >150.
      Finally, we have fabricated membrane-integrated microfluidic devices that can
      concentrate protein samples (R-phycoerythrin) over 10 000-fold to facilitate
      microchip capillary electrophoresis. Interfacing microchannels with ion-permeable
      membranes has great potential to enhance microchip analysis of biomolecules.

PMID- 16615766
TI  - Immunophenotyping of acute leukemias using a quartz crystal microbalance and
      monoclonal antibody-coated magnetic microspheres.
AB  - Immunophenotyping, which utilizes panels of lineage-associated monoclonal
      antibodies to recognize clusters of differentiation (CD) antigens expressed on
      various leukocytes, plays a key role in the clinical diagnosis of acute
      leukemias. In this paper, a rapid, simple, and automatic immunophenotyping
      technique for acute leukemias has been initially proposed by incorporating
      immunomagnetic separation and quartz crystal microbalance (QCM) measurement. Core
      shell paramagnetic microspheres of silica-coated ZnFe2O4 were newly fabricated
      following a W/O microemulsion route and further functionalized for anchoring
      separately CD antibodies of lineage-different leukocytes. The resultant
      immunomagnetic microspheres were introduced, in turn, to capture target
      leukocytes from the samples and were magnetically accumulated onto the protein A
      modified QCM to be analyzed. The response characteristics of the developed QCM
      system for immunophenotyping various lineage-defined leukocytes were investigated
      in detail. Results indicate that this new technique can allow for easy and clear
      identification of acute leukocytes of lymphoid and myeloid origins as well as
      their subsets. It may also permit the quantitative determination of acute
      leukocytes with cell concentration down to approximately 10(3) cells mL(-1).
      Moreover, the applicable feasibility of the QCM immunophenotyping method was
      validated through assessing a number of clinical specimens, which phenotypes are
      in acceptable agreement with those obtained by the immunoenzyme assay clinically
      used for this purpose.

PMID- 16615767
TI  - Identification and quantification of homologous series of compound in complex
      mixtures: autocovariance study of GC/MS chromatograms.
AB  - The paper describes a method for determining homologous classes of compounds in a
      multicomponent complex chromatogram obtained under programming elution
      conditions. The method is based on the computation of the autocovariance function
      of the experimental chromatogram (EACVF). The EACVF plot, if properly
      interpreted, can be regarded as a "class chromatogram" i.e., a virtual
      chromatogram formed by peaks whose positions and heights allow identification and
      quantification of the different homologous series, even if they are embedded in a
      random complex chromatogram. Theoretical models were developed to describe
      complex chromatograms displaying random retention pattern, ordered sequences or a
      combination of them. On the basis of theoretical autocovariance function, the
      properties of the chromatogram can be experimentally evaluated, under well
      defined conditions: in particular, the two components of the chromatogram,
      ordered and random, can be identified. Moreover, the total number of single
      components (SCs) and the separated number of the SCs belonging to the random and
      ordered components can be determined, when the two components display the same
      concentration. If the mixture contains several homologous series with common
      frequency and different phase values, the number and identity of the different
      homologous series as well as the number of SCs belonging to each of them can be
      evaluated. Moreover, the power of the EACVF method can be magnified by applying
      it to the single ion monitoring (SIM) signals to selectively detect specific
      compound classes in order to identify the different homologous series. By this
      way, a full "decoding" of the complex multicomponent chromatogram is achieved.
      The method was validated on synthetic mixtures containing known amount of SCs
      belonging to homologous series of hydrocarbon, alcohols, ketones, and aromatic
      compounds in addition to other not structurally related SCs. The method was
      applied to both the total ion monitoring (TIC) and the SIM signals, to describe
      step by step the essence of the procedure. Moreover, the systematic use of both
      SIM and TIC can simplify the decoding procedure of complex chromatograms by
      singling out only specific compound classes or by confirming the identification
      of the different homologous series. The method was further applied to a sample
      containing unknown number of compounds and homologous series (a petroleum benzin,
      bp 140-160 degrees C): the results obtained were meaningful in terms of both the
      identified number of components and identified homologous series.

PMID- 16615768
TI  - Matrix with high salt tolerance for the analysis of peptide and protein samples
      by desorption/ionization time-of-flight mass spectrometry.
AB  - High concentrations of urea and guanidine hydrochloride are commonly used for the
      denaturation of protein, which was digested by enzymatic proteolysis for the
      identification by MS analysis. The presence of these contaminants seriously
      suppresses the ion signal of analytes in MALDI-TOF MS analysis. Herein, a novel
      MALDI matrix, 3, 4-diaminobenzophenone (DABP), has been found with high tolerance
      for these contaminants in MALDI MS analysis. The ion signal of analyte insulin
      can be detected in the presence of 2 M guanidine hydrochloride and 1.5 M urea
      using DABP as matrix. The tryptic digest of BSA (400 fmol) in 1 M guanidine
      hydrochloride or 1 M urea was successfully analyzed without any pretreatment
      prior to MS analysis. Furthermore, it has been found that this matrix can also
      effectively suppress the cation ion adduction of the peptides in the presence of
      high concentrations of metal ions in sample solution.

PMID- 16615769
TI  - Correlation and convolution analysis of peptide mass spectra.
AB  - As proteomics continues to establish itself as an effective postgenomic research
      tool, there is an increasingly urgent need for efficient, automated analysis
      techniques capable of effectively dealing with the vast amounts of data generated
      via mass spectrometry. Wholesale analysis packages, often used to deal with these
      enormous amounts of data, may benefit from supplementary, targeted analyses as
      current research begins to emphasize posttranscriptional/translational protein
      modifications, protein truncations, and poorly characterized mutations. We
      demonstrate the application of a new analysis technique based on mathematical
      correlation that is computationally efficient and robust against different
      instruments, noise levels, and experimental conditions. We have previously shown
      that this technique is able to extract pertinent mass shift signals from MS data,
      corresponding to the neutral loss of a modification from a peptide, e.g., a loss
      of 79.97 Th from phosphorylated tyrosine. Here we show that an extension of this
      method is applicable to MS and MS/MS data in general, allowing visualization of
      ions that produce a particular mass shift signal, be it from differential stable
      isotope labeling, overlap of fragment ions in a series, or ions that produce a
      neutral loss. The application of this method allows the researcher to discover
      individual features, such as the presence of specific modified or isotopically
      labeled peptides, to eliminate overlapping fragment ion series, and to localize
      specific sites of modification.

PMID- 16615770
TI  - Aqueous-phase aminolysis: approach for the analysis of epoxides in water.
AB  - Trace concentrations of small soluble epoxides are suspected byproducts of
      drinking water ozonation. However, adequate characterization of epoxide formation
      is currently limited by the lack of suitable analytical methods to target these
      chemicals in dilute, but complex aqueous solutions. One potential approach is
      presented here based on aqueous-phase aminolysis. The method also employs solid
      phase extraction, silylation of the solvent extract, and analysis by gas
      chromatography-mass spectrometry. This approach is demonstrated to be effective
      for the selective analysis of the epoxides 1,2-epoxybutane, epichlorohydrin, and
      epifluorohydrin in water with optimized method detection limits of 5-10 ng/L.

PMID- 16615771
TI  - Quantification of farnesylmethylcysteine in lysates of peripheral blood
      mononuclear cells using liquid chromatography coupled with electrospray tandem
      mass spectrometry: pharmacodynamic assay for farnesyl transferase inhibitors.
AB  - Biological effectiveness is an important parameter in determining optimal dosages
      of molecular targeted drugs, such as farnesyl transferase inhibitors. To
      determine concentration-effect relationships, robust and quantitative biological
      assays are a prerequisite. Here, we present a novel assay for protein
      farnesylation that is based on generation of the biomarker farnesylmethylcysteine
      (FmC). Quantification was performed with liquid chromatography coupled to tandem
      mass spectrometry. The assay has been validated based on the most recent FDA
      guidelines for bioanalytical validation, and all results were within
      requirements. FmC is formed under the action of an endogenous protease that is
      activated upon cell lysis. The biomarker could be detected in A549 human lung
      cancer cells as well as in human peripheral blood mononuclear cells. Incubation
      of A549 cells with AZD3409, a novel prenyl transferase inhibitor, resulted in a
      significant decrease of the FmC concentration in the lysates. These findings
      provide a very good starting point for use of this assay in preclinical and
      clinical dose finding studies with FTIs.

PMID- 16615772
TI  - High-performance, static-coated silicon microfabricated columns for gas
      chromatography.
AB  - A procedure is described for the preparation of high-performance etched silicon
      columns for gas chromatography. Rectangular channels, 150 mum wide by 240 mum
      deep are fabricated in silicon substrates by gas-phase reactive ion etching. A
      0.1-0.2-mum-thick film of dimethyl polysiloxane stationary phase is deposited on
      the channel walls by filling the channel with a dilute solution in 1:1 n-pentane
      and dichloromethane and pumping away the solvent. A thermally activated cross
      linking agent is used for in situ cross-linking. A 3-m-long microfabricated
      column generated approximately 12 500 theoretical plates at optimal operating
      conditions using air as carrier gas. A kinetic model for the efficiency of
      rectangular cross-section columns is used to evaluate column performance. Results
      indicate an additional source of gas-phase dispersion beyond longitudinal
      diffusion and nonequilibrium effects, probably resulting from numerous turns in
      the gas flow path through the channel. The columns are thermally stable to at
      least 180 degrees C using air carrier gas. Temperature programming is
      demonstrated for the boiling point range from n-C5 to n-C12. A 3.0-m-long column
      heated at 10 degrees C/min obtains a peak capacity of over 100 peaks with a
      resolution of 1.18 and a separation time of approximately 500 s. With a 0.25-m
      long column heated at 30 degrees C/min, a peak capacity of 28 peaks is obtained
      with a separation time of 150 s. Applications are shown for the analysis of air
      phase petroleum hydrocarbons and the high-speed analysis of chemical warfare
      agent and explosive markers.

PMID- 16615773
TI  - Method for the determination of inorganic polysulfide distribution in aquatic
      systems.
AB  - Inorganic polysulfides have significant technological importance, and their
      environmental role is gradually being unraveled. But despite their importance,
      there is still no method for quantification of the individual members of the
      polysulfide family in nonsynthetic samples. The method is based on fast, single
      phase derivatization with methyl trifluoromethanesulfonate followed by one of
      three modes of sample treatment depending on polysulfide concentration. Under the
      most aggressive preconcentration treatment involving liquid-liquid extraction,
      solvent evaporation to dryness, dissolution in n-dodecane, and finally HPLC-UV
      analysis of the dimethylpolysulfane distribution, the minimum detection limits of
      the individual polysulfides are in the range 15-70 nM. The method was
      demonstrated for the analysis of synthetic solutions, natural groundwater,
      polysulfide fortified seawater, and surface water and for time tracing of the
      distribution of the individual polysulfides during the oxidation of hydrogen
      sulfide by hydrogen peroxide. The observed speciation was evaluated by comparison
      with the theoretical distribution of polysulfides at equilibrium with sulfur
      precipitate showing that the dominant polysulfides' (i.e., tetra- to hexasulfide)
      concentrations agree well with the predicted distribution (90% of the results
      fall within less than 30% deviation from the predicted values), whereas up to 3
      fold deviation was observed for the less abundant trisulfide and octasulfide
      species.

PMID- 16615774
TI  - On-line HPLC-UV/Nano-TiO2-ICPMS system for the determination of inorganic
      selenium species.
AB  - We have developed an UV/nano-TiO2 vapor generation (VG) device that when coupled
      between a chromatographic column and an ICP mass spectrometer provides a simple
      and sensitive hyphenated method for the determination of Se(IV) and Se(VI)
      without the need to use conventional chemical VG techniques. Because our proposed
      VG device allows both Se(IV) and Se(VI) species in the column effluent to be
      converted on-line into volatile Se products, which are then measured directly by
      the ICPMS, the safety risks and the probability of contamination arising from the
      use of additional chemicals are both low. To achieve the maximum signal
      intensity, we optimized a number of the operating parameters of the UV/nano-TiO2
      VG device, including the acidity, the amounts of TiO2 and formic acid, and the
      length of the reaction coil, with respect to their effects on the reduction
      efficiency of the analyte species. This hyphenated method achieves excellent
      detection limits-0.06 and 0.03 ng mL(-1) for Se(IV) and Se(VI), respectively
      because of the high efficiencies of the conversions of Se(IV) and Se(VI) to their
      respective volatile products and the lower blank level achieved, relative to
      those of other traditional systems. In addition, because the conversion
      efficiency of the analyte selenium species reached its maximum level within 36 s
      of irradiation, the working time (approximately 12 min) was limited primarily by
      time required for the chromatographic separation. A series of validation
      experiments-analysis of the 1643e Standard Reference Material and natural water
      samples-indicated that our proposed methods can be applied satisfactorily to the
      determination of inorganic selenium species in water samples.

PMID- 16615775
TI  - Circular dichroism thermal lens microscope for sensitive chiral analysis on
      microchip.
AB  - A novel chiral detector, a circular-dichroism thermal lens microscope (CD-TLM),
      was developed to realize sensitive and selective detection of small volume chiral
      samples on a microchip. To realize chiral recognition on TLM, an excitation beam
      was phase-modulated at a frequency of 1.2 kHz, and left-circularly polarized
      light (LCPL) and right-circularly polarized light (RCPL) were generated. Then,
      the differential light absorption between LCPL and RCPL, which is the CD effect,
      was detected as thermal lens signal intensity and phase. As a standard sample,
      optically active tris(ethylenediamine)cobalt(III) [Co-(en)3]3+I3- aqueous
      solutions were used for performance evaluations. First, we verified the basic
      principle for selective chiral analysis by comparing the signals in intensity
      modulation and phase-modulation modes of the excitation beam. Also, we found that
      the g-factor, which is significant for determining enantiomeric excess, agreed
      well with the value obtained by the CD spectrometer. The limit of detection (LOD)
      for enantiopure [Co-(en)3]3+I3- was 6.3 x 10(-5) M (1.9 x 10(-7) abs) for (-)
      Co(en)3(3+), and the sensitivity in absorbance units was more than 250 times
      higher than that in a CD spectrophotometer. Finally, we demonstrated enantiomeric
      excess determination on a microchip. The LOD was 1.7% (8.5 x 10(-7) abs) for (-)
      Co(en)3(3+) and at least one order superior to the LOD of a CD spectrometer. The
      applicability of CD-TLM for sensitive chiral analysis on a microchip was
      verified, and CD-TLM is expected to be promising for microchip-based chiral
      synthesis and analysis systems.

PMID- 16615776
TI  - Electrochemical properties of carbon nanotube (CNT) film electrodes prepared by
      controllable adsorption of CNTs onto an alkanethiol monolayer self-assembled on
      gold electrodes.
AB  - This paper describes electrochemical properties, such as electrode reactivity,
      electrode dimensions, and interfacial capacitance, of multiwalled carbon nanotube
      (MWNT) film electrodes prepared by controllable adsorption of the MWNTs onto the
      self-assembled monolayer (SAM) of n-octadecyl mercaptan (C18H37SH) deposited onto
      Au electrodes. The adsorption of the MWNTs onto the SAM-modified Au electrode
      substantially restores heterogeneous electron transfer between bare Au electrode
      and redox species in solution phase that is almost totally blocked by the SAM of
      C18H37SH, and as a result, the prepared MWNT/SAM-modified electrode possesses
      good electrode reactivity without a remarkable barrier to heterogeneous electron
      transfer. In addition, the surface coverage of the MWNTs is readily controlled by
      adjusting the immersion time for the adsorption of the MWNTs onto the SAM of
      C18H37SH, which essentially endows the prepared MWNT/SAM-modified electrodes with
      tunable electrode dimensions ranging from a nanoelectrode array to a macro-sized
      conventional electrode. On the other hand, the MWNT/SAM-modified electrode is
      found to possess a largely reduced interfacial capacitance, as compared with the
      MWNT film electrodes prepared with existing methods by directly confining the
      MWNTs onto electrode surface. This demonstration offers a new approach to
      fabrication of stable MWNT film electrodes with excellent electrochemical
      properties that are believed to be very attractive for electrochemical studies
      and electroanalytical applications.

PMID- 16615777
TI  - Pulsation modes and the effect of applied voltage on current and flow rate in
      nanoelectrospray.
AB  - New modes of nanoelectrospray (nES) have been identified that exhibit stable high
      frequency current oscillations in the kilohertz range. In-line flow rate
      measurements during nES have for the first time allowed the accurate
      determination of the spray current and volumetric flow rate dependence on applied
      voltage. High-speed video imaging has revealed that each current pulse
      corresponds to the periodic formation of a short-lived stable cone-jet structure
      at the capillary tip. These findings are of particular importance and suggest
      greater process monitoring and control in nES-MS systems is necessary if
      efficiency and ion yield are to be optimized.

PMID- 16615778
TI  - Open tubular capillary electrochromatography: technique for oxidation and
      interaction studies on human low-density lipoproteins.
AB  - A novel, open tubular capillary electrochromatographic method was developed for
      the in vitro oxidation of low-density lipoprotein (LDL) particles. Low-density
      lipoprotein particles with molar mass of approximately 2.5 MDa yielded a stable
      stationary phase at temperatures 25 and 37 degrees C and at pH values from 3.2 to
      7.4. The quality of the coatings was not influenced by variations in the LDL
      concentration in the coating solutions (within the range of 2-0.015 mg/mL) with
      the coating procedure used in the study. Radiolabeled LDL stationary phases and
      scanning electron microscopy, employed to shed light on the location and coating
      density of LDL particles on the inner surface of the capillary wall, confirmed
      the presence of an LDL monolayer and almost 100% coating efficiency (99 +/- 8%).
      In addition, the radioactivity measurements allowed estimation of the amount of
      LDL present in a single capillary coating. Capillaries coated with human LDL
      particles were submitted to different oxidative conditions by changing the
      concentration of the oxidant (CuSO4), oxidation time, pH value, and temperature.
      The oxidation procedure was followed with electroosmotic flow mobility, which
      served as an indicator of the increase in total negative charges of LDL coatings,
      and by asymmetrical field flow fractionation, which measured the changes in size
      of the lipoprotein particles. The results indicated that oxidation of LDL was
      progressing with increasing time, temperature, and concentration of the oxidant
      as expected. The oxidation process was faster around neutral pH values (pH 6.5
      7.4) and inhibited at acidic pH values (pH 5.5 and lower).

PMID- 16615780
TI  - Temperature profiles and heat dissipation in capillary electrophoresis.
AB  - While temperature control is usually employed in capillary electrophoresis (CE)
      to aid heat dissipation and provide acceptable precision, internal electrolyte
      temperatures are almost never measured. In principle, this limits the accuracy,
      repeatability, and method robustness. This work presents a fundamental study that
      combines the development of new equations characterizing temperature profiles in
      CE with a new method of temperature determination. New equations were derived
      from first principles relating the mean, axial, and inner wall electrolyte
      temperatures (T(Mean), T(Axis), T(Wall)). T(Mean) was shown to occur at a
      distance 1/ radical3 times the internal radius of the capillary from the center
      of the capillary and to be a weighted average of (2/3)T(Axis) and (1/3)T(Wall).
      Conductance (G) and electroosmotic mobility (mu(EOF)) can be used to determine
      T(Mean) and T(Wall), respectively. Extrapolation of curves of mu(EOF) versus
      power per unit length (P/L) at different temperatures was used to calibrate the
      variation of mu(EOF) with temperature (T), free from Joule heating effects.
      mu(EOF) increased at 2.22%/ degrees C. The experimentally determined temperatures
      using mu(EOF) agreed to within 0.2 degrees C with those determined using G. The
      accuracy of G measurements was confirmed independently by measuring the
      electrical conductivity (kappa) of the bulk electrolyte over a range of
      temperatures and by calculating the variation of G with T from the Debye-Huckel
      Onsager equation. T(Mean) was found to be up to 20 degrees C higher than the
      external temperature under typical conditions using active air-cooling and a 74.0
      microm-internal diameter (di) fused-silica capillary. A combination of
      experimentally determined and calculated temperatures enables a complete
      temperature profile for a fused-silica capillary to be drawn and the thickness of
      the stationary air layer to be determined. As an example, at P/L = 1.00 Wm(-1),
      the determined radial temperature difference across the electrolyte was 0.14
      degrees C; the temperature difference across the fused-silica wall was 0.17
      degrees C, across the poly(imide) coating was 0.13 degrees C, and across the
      stationary air layer was 2.33 degrees C.

PMID- 16615779
TI  - Quantitative studies of allosteric effects by biointeraction chromatography:
      analysis of protein binding for low-solubility drugs.
AB  - A new chromatographic method was developed for characterizing allosteric
      interactions between an immobilized binding agent and low-solubility compounds.
      This approach was illustrated by using it to characterize the interactions
      between tamoxifen and warfarin during their binding to the protein human serum
      albumin (HSA), with beta-cyclodextrin being employed as a solubilizing agent for
      these drugs. It was confirmed in this work through several experiments that
      warfarin had a single binding site on HSA with an association equilibrium
      constant of (2-5) x 10(5) M(-1) (average, 3.9 x 10(5) M(-1)) at 37 degrees C, in
      agreement with previous reports. It was also found that tamoxifen had a single
      major binding site on HSA, with an association equilibrium constant of (3-4) x
      10(7) M(-1) (average, 3.5 x 10(7) M(-1)) at 37 degrees C. When warfarin was used
      as a mobile-phase additive in competition studies with tamoxifen, this had a
      positive allosteric effect on tamoxifen/HSA binding, giving a coupling constant
      of 2.3 (+/-0.3). Competitive studies using tamoxifen as a mobile-phase additive
      indicated that tamoxifen had a negative allosteric effect on warfarin/HSA
      binding, providing a coupling constant of 0.79 (+/-0.03). A unique feature of the
      technique described in this report was its ability to independently examine both
      directions of the warfarin/tamoxifen allosteric interaction. This approach is not
      limited to warfarin, tamoxifen, and HSA but can also be used to study other
      solutes and binding agents.

PMID- 16615781
TI  - Electrogenerated chemiluminescence detection of amino acids based on precolumn
      derivatization coupled with capillary electrophoresis separation.
AB  - A novel method for highly sensitive detection of primary and secondary amino
      acids with selective derivatization using acetaldehyde as a new derivatization
      reagent was proposed by capillary electrophoresis (CE) coupled with
      electrogenerated chemiluminescence (ECL) of tris(2,2'-bipyridine)ruthenium(II).
      The precolumn derivatization of these amino acids with acetaldehyde was performed
      in aqueous solution at room temperature for 1 h. Upon optimized derivatization,
      the ECL intensities and detection sensitivities of the amino acids were
      significantly enhanced by 20-70 times. Using four amino acids, arginine, proline,
      valine, and leucine, as model compounds, their derivatives could be completely
      separated by CE and sensitively detected by ECL within 22 min. The linear ranges
      were 0.5-100 microM for arginine and proline and 5-1000 microM for valine and
      leucine with the detection limits of 1 x 10(-7) (0.5 fmol, arginine), 8 x 10(-8)
      (0.4 fmol, proline), 1 x 10(-6) (5 fmol, valine), and 1.6 x 10(-6) M (8 fmol,
      leucine) at a signal-to-noise ratio of 3. The derivatization reactions and ECL
      process of amino acids were also proposed based on in situ Fourier transform
      infrared and ultraviolet spectrometric analyses.

PMID- 16615782
TI  - Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry
      analysis of metabolites in fermenting and respiring yeast cells.
AB  - Comprehensive two-dimensional gas chromatography with time-of-flight mass
      spectrometry coupled with rapid chemometric analysis were used to identify
      chemical differences in metabolite extracts isolated from yeast cells either
      metabolizing glucose (repressed (R) cells) via fermentation or metabolizing
      ethanol by respiration (derepressed (DR) cells). Principal component analysis
      (PCA) followed by parallel factor analysis (PARAFAC) in concert with the LECO
      ChromaTOF software located and identified the differences in composition between
      the two types of cell extracts and provided a reliable ratio of the metabolite
      concentrations. In this report, we demonstrate the analytical method developed to
      provide relatively rapid analysis of three selective mass channels (m/z 73, 205,
      387), although in principle all collected mass channels could be analyzed. Twenty
      six metabolites that differentiate repressed cells from derepressed cells were
      identified. The DR/R ratio of metabolite concentrations ranged from 0.02 for
      glucose to 67 for trehalose. The average biological variation of the sample
      extracts was 31%. This analysis demonstrates the utility and benefit of using PCA
      combined with PARAFAC and ChromaTOF software on extremely complex samples to
      derive useful information from complex three-dimensional chromatographic data
      objectively and relatively rapidly.

PMID- 16615783
TI  - Redox polymer and probe DNA tethered to gold electrodes for enzyme-amplified
      amperometric detection of DNA hybridization.
AB  - The detection of nucleic acids based upon recognition surfaces formed by co
      immobilization of a redox polymer mediator and DNA probe sequences on gold
      electrodes is described. The recognition surface consists of a redox polymer,
      [Os(2,2'-bipyridine)2(polyvinylimidazole)(10)Cl](+/2+), and a model single DNA
      strand cross-linked and tethered to a gold electrode via an anchoring self
      assembled monolayer (SAM) of cysteamine. Hybridization between the immobilized
      probe DNA of the recognition surface and a biotin-conjugated target DNA sequence
      (designed from the ssrA gene of Listeria monocytogenes), followed by addition of
      an enzyme (glucose oxidase)-avidin conjugate, results in electrical contact
      between the enzyme and the mediating redox polymer. In the presence of glucose,
      the current generated due to the catalytic oxidation of glucose to gluconolactone
      is measured, and a response is obtained that is binding-dependent. The tethering
      of the probe DNA and redox polymer to the SAM improves the stability of the
      surface to assay conditions of rigorous washing and high salt concentration (1
      M). These conditions eliminate nonspecific interaction of both the target DNA and
      the enzyme-avidin conjugate with the recognition surfaces. The sensor response
      increases linearly with increasing concentration of target DNA in the range of 1
      x 10(-9) to 2 x 10(-6) M. The detection limit is approximately 1.4 fmol,
      (corresponding to 0.2 nM of target DNA). Regeneration of the recognition surface
      is possible by treatment with 0.25 M NaOH solution. After rehybridization of the
      regenerated surface with the target DNA sequence, >95% of the current is
      recovered, indicating that the redox polymer and probe DNA are strongly bound to
      the surface. These results demonstrate the utility of the proposed approach.

PMID- 16615784
TI  - Selectivity in the coextraction of cation and anion by electrochemically
      modulated liquid-liquid extraction.
AB  - Electrochemistry at the interface between two immiscible electrolyte solutions
      has been presented as a method of electrochemically modulated liquid-liquid
      extraction, where ions in a mixture can be selectively partitioned as a function
      of the applied interfacial potential difference. In this study, a mixture
      comprising 4-octylbenzenesulfonate (4-OBSA-) and tetraethylammonium (TEA+) ions
      was evaluated. The application of negative potential differences enabled the
      selective extraction of 4-OBSA- into the organic phase, and more positive
      potential differences enabled the selective extraction of TEA+. However,
      intermediate potentials lead to the coextraction of both ions into the organic
      phase, with apparent selectivity for TEA+ over 4-OBSA-. An increased
      concentration of either ion in the mixture inhibited the extraction response of
      the other ion, but the order of the extraction at these intermediate potentials
      was always TEA+ followed by 4-OBSA-. The reasons for the selectivity for the
      cation over the anion are discussed.

PMID- 16615785
TI  - Wide electrochemical window at the interface between water and a hydrophobic room
      temperature ionic liquid of tetrakis[3,5-bis(trifluoromethyl)phenyl]borate.
AB  - Ionic liquids composed of a hydrophobic anion, tetrakis[3,5
      bis(trifluoromethyl)phenyl]borate (TFPB-), and various aromatic and aliphatic
      ammonium have been prepared. TFPB salts of N-octadecylisoquinolinium (C18Iq+) and
      trioctylmethylammonium (TOMA+) show low melting points of 31 and 36 degrees C,
      respectively, whereas TFPB-based ionic liquids of 1-alkyl-3-methylimidazolium
      with the alkyl chain length of 5-12 show melting points lower than 90 degrees C.
      The [C(18)Iq][TFPB]|water (W) and [TOMA][TFPB]|W interfaces have the polarized
      potential window (ppw) of 0.8 V at 56 degrees C, which is twice as wide as the
      ppw at the interface between W and room-temperature ionic liquids of
      bis(perfluoroalkylsulfonyl)imide so far reported. The extension of the ppw by
      more than 0.4 V to the positive direction enables voltammetric measurements of
      the ion transfer of relatively hydrophobic anions such as
      bis(trifluoromethylsulfonyl)imide and bis(pentafluoroethylsulfonyl)imide and of
      hydrophilic cations such as tetraethylammonium and acetylcholine ions.

PMID- 16615786
TI  - Label-free detection of single protein molecules using deep UV fluorescence
      lifetime microscopy.
AB  - We present the detection of single beta-galactosidase molecules from Escherichia
      coli (Ecbeta Gal) using deep UV laser-based fluorescence lifetime microscopy. The
      native fluorescence from intrinsic tryptophan emission has been observed after
      one-photon excitation at 266 nm. Applying the time-resolved single-photon
      counting method, we investigated the fluorescence lifetime distribution and the
      bursts of autofluorescence photons from tryptophan residues in Ecbeta Gal protein
      as well as fluorescence correlation spectroscopy of Ecbeta Gal. The results
      demonstrate that deep UV laser-based fluorescence lifetime microscopy is useful
      for identification of biological macromolecules at the single-molecule level
      using intrinsic fluorescence.

PMID- 16615787
TI  - Preliminary investigation of proton and helium ion radiation effects on
      fluorescent dyes for use in astrobiology applications.
AB  - The Specific Molecular Identification of Life Experiment (SMILE) instrument (Sims
      et al. Planet. Space Science 2005, 53, 781-791) proposes to use specific
      molecular receptors for the detection of organic biomarkers on future
      astrobiology missions (e.g., to Mars). Such receptors will be used in assays with
      fluorescently labeled assay reagents. A key uncertainty of this approach is
      whether the fluorescent labels used in the system will survive exposure to levels
      of solar and galactic particle radiation encountered during a flight to Mars.
      Therefore, two fluorescent dyes (fluorescein and Alexa Fluor 633) have been
      exposed to low-energy proton and alpha radiation with total fluences comparable
      or exceeding that expected during an unshielded cruise to Mars. The results of
      these initial experiments are presented, which show that both dyes retain their
      fluorescent properties after irradiation. No significant alteration in the
      absorption and emission wavelengths or the quantum yields of the dyes with either
      radiation exposure was found. These results suggest other structurally similar
      fluorophores will likely retain their fluorescent properties after exposure to
      similar levels of proton and alpha radiation. However, more extensive radiation
      fluorophore testing is needed before their suitability for astrobiology missions
      to Mars can be fully confirmed.

PMID- 16615788
TI  - Calcium pulstrodes with 10-fold enhanced sensitivity for measurements in the
      physiological concentration range.
AB  - Ion-selective electrodes ideally operate on the basis of the Nernst equation,
      which predicts less than 60- and 30-mV potential change for a 10-fold activity
      change of monovalent and divalent ions measured at room temperature,
      respectively. Typical concentration ranges in extracellular fluids are quite
      narrow for the electrolytes of key importance. A range of 2.2-2.6 mM for calcium
      ions, for instance, translates into just a 2.2-mV potential change. The direct
      potentiometric measurement of physiological electrolytes is certainly possible
      with direct potentiometry and is done routinely in clinical analyzers and
      handheld measuring devices. It places, however, strong demands on the precision
      of the reference electrode and requires careful temperature control and frequent
      calibration runs. In this paper, a robust 10-20-fold sensitivity enhancement for
      calcium measurements is attained by departing from the classical response
      mechanism and operating in a non-Nernstian response mode. Stable and reproducible
      super-Nernstian responses of these so-called pulstrodes in a narrow calcium
      activity range can be controlled by instrumental means in good agreement with
      theory. The potentials may be measured during a galvanostatic excitation pulse
      (mode I) or immediately after it (mode II), under open-circuit conditions.
      Subtraction of the potentials, sampled at different times during a single pulse,
      allows one to obtain a sensitive differential peak-shaped signal at a critical
      and fully adjustable analyte activity range. Calcium pulstrodes based on the
      diamide ionophore AU-1 were characterized and applied to the measurement in model
      physiological liquids. Super-Nernstian responses exceeding 700 mV/decade were
      observed in a physiological range of calcium concentration. Such remarkable
      sensitivity of the pulstrodes, complemented with the well-documented high
      selectivity of these potentiometric sensors, may provide a significant increase
      in the accuracy and precision of electrolyte measurements in clinical analysis.

PMID- 16615789
TI  - Determination of Intramolecular delta13C from incomplete pyrolysis fragments.
      Evaluation of pyrolysis-induced isotopic fractionation in fragments from the
      lactic acid analogue propylene glycol.
AB  - Intramolecular carbon isotope ratios reflect the source of a compound and the
      reaction conditions prevailing during synthesis and degradation. We report here a
      method for determination of relative (Deltadelta13C) and absolute (delta13C)
      intramolecular isotope ratios using the volatile lactic acid analogue propylene
      glycol as a model compound, measured by on-line gas chromatography-pyrolysis
      coupled to GC-combustion-isotope ratio mass spectrometry. Pyrolytic fragmentation
      of about one-third of the analyte mass produces optimal fragments for isotopic
      analysis, from which relative isotope ratios (Deltadelta13C) are calculated
      according to guidelines presented previously. Calibration to obtain absolute
      isotope ratios is achieved by quantifying isotope fractionation during pyrolysis
      with an average fractionation factor, alpha, and evaluated by considering
      extremes in isotopic fractionation behavior. The method is demonstrated by
      calculating ranges of absolute intramolecular isotope ratios in four samples of
      propylene glycol. Relative and absolute isotope ratios were calculated with
      average precisions of SD(Deltadelta13C) <0.84 per thousand and SD(delta13C) <3.0
      per thousand, respectively. The various fractionation scenarios produce an
      average delta(13)C range of 2 per thousand for each position in each sample.
      Relative isotope ratios revealed all four samples originated from unique sources,
      with samples A, B, and D only distinguishable at the position-specific level.
      Regardless of pyrolysis fractionation distribution, absolute isotope ratios
      showed a consistent pattern for all samples, with delta13C(3) > delta13C(2) >
      delta13C(1). The validity of the method was determined by examining the
      difference in relative isotope ratios calculated through two independent methods:
      Deltadelta13C calculated directly using previous methods and Deltadelta13C
      extracted from absolute isotope ratios. Deviation between the two Deltadelta13C
      values for all positions averaged 0.1-0.2 per thousand, with the smallest
      deviation obtained assuming equal fractionation across all fragment positions.
      This approach applies generally to all compounds analyzed by pyrolytic PSIA.

PMID- 16615790
TI  - Use of pulsed gradient spin-echo NMR as a tool in MALDI method development for
      polymer molecular weight determination.
AB  - This study shows how mass spectrometry and pulsed gradient spin-echo (PGSE)
      nuclear magnetic resonance can be advantageously combined to achieve more
      reliable molecular weight information for polymers. Specifically, PGSE was shown
      to be a convenient tool for a rapid evaluation of Mw values to be further used as
      guidelines in matrix-assisted laser desorption/ionization (MALDI) sample
      preparation. PGSE calibration curves, established under given experimental
      conditions, were shown to be particularly robust, as they could be applied
      satisfactorily on different commonly available NMR instruments and different time
      frames. PGSE results were shown to compare well with size exclusion
      chromatography data used as a reference to validate this alternative technique.
      Moreover, because PGSE is relatively fast, it can be used interactively with
      MALDI analysis to check and understand mass spectrum profiles. This approach was
      first tested on poly(methyl methacrylate) (PMMA) standards and then successfully
      applied to determine the molecular weight of two unknown samples, a PMMA and a
      poly(ethylene glycol) monomethacrylate polymer.

PMID- 16615791
TI  - Invisible analyte peak deformations in single-component liquid chromatography.
AB  - It is well known that if a small excess of solute is injected into a
      chromatographic system equilibrated with an eluent containing the same solute, a
      single so-called perturbation peak will appear in the chromatogram. It was
      recently shown (Samuelsson, J.; Forssen, P.; Stefansson, M.; Fornstedt, T. Anal.
      Chem. 2004, 76, 953-958) that this peak consists of displaced plateau molecules;
      the injected molecules (mass peak) elute later, together with a deficiency of
      plateau molecules and are therefore not detected. In this article, we
      investigated what happens if a large rather than a small excess of solute
      molecules is injected. To study this systematically, the experimental method
      involved an enantiomer pair in an achiral separation system. It was found that
      the invisible mass peak was extremely deformed and that its shape depended on the
      amount of excess injected, the eluent concentration, and the column length.
      Depending on these operational conditions, the mass peak changed from a classical
      Langmuirian (tailing) to an anti-Langmuirian (leading) shape, with deformed
      shapes observable in the transition. The visible, overloaded perturbation peak
      was always Langmuirian, regardless of the mass peak shape.

PMID- 16615792
TI  - Approaches for the simultaneous extraction of tetrabromobisphenol A,
      tetrachlorobisphenol A, and related phenolic compounds from sewage sludge and
      sediment samples based on matrix solid-phase dispersion.
AB  - A procedure based on matrix solid-phase dispersion (MSPD) for sample preparation
      in the analysis of some bromophenols and halogenated bisphenols in sediments and
      sludges has been developed. For the first time ever, MSPD was applied for the
      extraction of organic contaminants from sediment and sewage sludge samples. The
      influence of experimental conditions on the yield of the extraction process and
      on the efficiency of the built-in cleanup step was thoroughly evaluated. Analysis
      of the extracts was performed by nonaqueous capillary electrophoresis coupled
      with photodiode array ultraviolet detection, using large-volume sample stacking
      injection based on the electroosmotic flow pump as an on-column preconcentration
      technique. The method was applied to the analysis of real sludges from urban
      sewage treatment plants, as well as river and marine sediment samples.

PMID- 16615793
TI  - Ion-pair chromatographic separation of water-soluble gold monolayer-protected
      clusters.
AB  - We demonstrate the efficacy of ion-pair chromatography for separations of samples
      of charged, polydisperse, water-soluble gold nanoparticles protected by
      monolayers of N-acetyl-l-cysteine and of tiopronin ligands. These nanoparticle
      mixtures have 1-2-nm-diameter Au core sizes as estimated from UV-visible spectra
      of the separated components. This size range encompasses the transition from bulk
      metal to molecular properties. The nanoparticle mixtures were resolved, the
      smallest nanoparticles eluting first, on an octadecylsilyl (C18) column using
      isocratic elution with a methanol/water mobile phase containing
      tetrabutylammonium fluoride (Bu4N+F-) and phosphate buffer. The column retention
      increases with Bu4N+F- concentration, lowered pH, and decreasing methanol volume
      fraction. The retention mechanism is dominated by ion-pairing in either the
      mobile phase or at the stationary/mobile-phase interface. Size exclusion effects,
      used in many previous nanoparticle separations, are insignificant.

PMID- 16615794
TI  - Soap bubbles in analytical chemistry. Conductometric determination of sub-parts
      per million levels of sulfur dioxide with a soap bubble.
AB  - Soap bubbles provide a fascinating tool that is little used analytically. With a
      very low liquid volume to surface area ratio, a soap bubble can potentially
      provide a very useful interface for preconcentration where mass transfer to an
      interfacial surface is important. Here we use an automated system to create
      bubbles of uniform size and film thickness. We utilize purified Triton-X 100, a
      nonionic surfactant, to make soap bubbles. We use such bubbles as a gas-sampling
      interface. Incorporating hydrogen peroxide into the bubble provides a system
      where electrical conductance increases as the bubble is exposed to low
      concentrations of sulfur dioxide gas. We theoretically derive the conductance of
      a hollow conducting spherical thin film with spherical cap electrodes. We measure
      the film thickness by incorporating a dye in the bubble making solution and laser
      transmission photometry and find that it agrees well with the geometrically
      computed thickness. With the conductance of the bubble-making soap solution being
      measured by conventional methods, we show that the measured values of the bubble
      conductance with known bubble and electrode dimensions closely correspond to the
      theoretically computed value. Finally, we demonstrate that sub-ppm levels of
      SO(2) can readily be detected by the conductivity change of a hydrogen peroxide
      doped soap bubble, measured in situ, when the gas flows around the bubble.

PMID- 16615795
TI  - Evaluation of corrosion potential measurements as a means to monitor the storage
      and stabilization processes of archaeological copper-based artifacts.
AB  - The focus of this study consists of examining how corrosion potential
      measurements can contribute in providing information on the effectiveness of
      storage and stabilization treatments of copper alloys in aqueous solutions. We
      report on the electrochemical behavior of artificial copper alloy coupons
      (covered or not with corrosion layers), simulating the behavior of real
      artifacts, immersed in sodium sesquicarbonate solutions. Particular attention is
      given to the transformation of the corrosion layer as a function of time. In
      addition, synchrotron radiation X-ray diffraction measurements are performed
      before and after the treatment in order to understand the reactions that take
      place during the immersion processes.

PMID- 16615796
TI  - IMS-IMS and IMS-IMS-IMS/MS for separating peptide and protein fragment ions.
AB  - Multidimensional ion mobility spectrometry (IMS-IMS and IMS-IMS-IMS) techniques
      have been combined with mass spectrometry (MS) and investigated as a means of
      generating and separating peptide and protein fragment ions. When fragments are
      generated inside a drift tube and then dispersed by IMS prior to MS analysis, it
      is possible to observe many features that are not apparent from MS analysis
      alone. The approach is demonstrated by examining fragmentation patterns arising
      from electrospray ion distributions of insulin chain B and ubiquitin. The
      multidimensional IMS approach makes it possible to select individual components
      for collisional activation and to disperse fragments based on differences in
      mobility prior to MS analysis. Such an approach makes it possible to observe many
      features not apparent by MS analysis alone.

PMID- 16615797
TI  - Verification of antiparallel G-quadruplex structure in human telomeres by using
      two-photon excitation fluorescence lifetime imaging microscopy of the 3,6-Bis(1
      methyl-4-vinylpyridinium)carbazole diiodide molecule.
AB  - Different G-quadruplex structures for the human telomeric sequence d(T2AG3)4 in
      vitro have been documented in the presence of sodium and potassium. Verification
      of the G-quadruplex structures in human telomeres in vivo is the main issue in
      establishing the biological function of the G-quadruplex structures in telomeres
      as well as the development of anticancer agents. Here we have applied two-photon
      excitation fluorescence lifetime imaging microscopy to measure the fluorescence
      lifetime of the BMVC molecule upon interaction with various DNA structures. The
      distinction in lifetime measured with submicrometer spatial resolution in two
      photon excitation fluorescence lifetime imaging microscopy provides a powerful
      approach not only to verify the existence of the antiparallel G-quadruplex
      structure in human telomeres but also to map its localizations in metaphase
      chromosomes.

PMID- 16615798
TI  - Fabrication of optically transparent carbon electrodes by the pyrolysis of
      photoresist films: approach to single-molecule spectroelectrochemistry.
AB  - This paper describes the preparation, physical and chemical characterization, and
      performance of carbon-based optically transparent electrodes (C-OTEs) fabricated
      by the pyrolysis of thin films of photoresist. The electrodes are prepared by
      spin coating dilute solutions of the positive photoresist AZ 4330 onto quartz
      substrates. Pyrolysis of these samples at 1000 degrees C in a reducing atmosphere
      yields optically transparent carbon films that have thicknesses ranging between
      10 and 80 nm. Sheet resistance measurements, X-ray photoelectron spectroscopy,
      Raman spectroscopy, and atomic force microscopy were used to determine the
      physical and chemical properties of the films, and cyclic voltammetry and
      chronoabsorptometry were employed to delineate the electrochemical and
      conventional spectroelectrochemical performance of the C-OTEs. These findings
      showed that the transparency of this material improves as film thickness
      decreases, but at the expense of an increase in film resistance. At a wavelength
      of 500 nm, for example, 13- and 79-nm-thick films have transparencies of 47 and
      10% and sheet resistances of 1100 and 210 Omega/ square, respectively.
      Importantly, adjusting the dilution factor allows the facile and reproducible
      variation of thickness and transparency. Preliminary results using these C-OTEs
      for single-molecule spectroelectrochemistry, which represents a new development
      in the merger of optical and electrochemical techniques, by probing the potential
      dependence of the adsorption of individual YOYO-I-labeled lambda-DNA are also
      presented.

PMID- 16615799
TI  - Results with an apparatus for pressurized planar electrochromatography.
AB  - Pressurized planar electrochromatography (PPEC) is a fast and efficient planar
      chromatographic technique. The mobile phase is driven by electroosmotic flow,
      while the system is pressurized in a manner that allows heat to flow between the
      sorbent layer and the pressurizing medium. The reproducibility of solute
      retention was not satisfactory in the initial report describing PPEC. In the
      current report, this reproducibility is improved by better control of several
      experimental variables. The pressure at which PPEC is performed is now free of
      drift, and the temperature at which the layer is preconditioned is maintained to
      within +/-1 degrees C. The best reproducibility of retention is obtained when the
      plate is soaked in the mobile phase for a defined time before each run. In the
      original prototype, the temperature of the sorbent layer was not controlled. In
      the present apparatus, water, at a constant temperature between 3 and 60 degrees
      C, is circulated through channels in the two die blocks that pressurize the
      layer. The highest efficiency is obtained at an intermediate temperature. This
      behavior is ascribed to high resistance to mass transfer at the lower
      temperatures and increased diffusion at higher temperatures. Efficiency, as
      measured by the number of theoretical plates, increases with increasing migration
      distance. The height equivalent of a theoretical plate diminishes with increasing
      migration distance, and values as low as 0.0106 mm are obtained under appropriate
      conditions. This extrapolates to 94 000 plates/m. Manual spotting was used in
      this report. Evidence is presented that substantially better efficiency would be
      obtained if the initial spot size were smaller. The efficiency of PPEC in its
      current form is illustrated by a chromatogram showing the separation of nine
      solutes in 2 min. PPEC was also performed with TLC plates in a back-to-back
      configuration, and this doubles the number of samples that can be simultaneously
      separated.

PMID- 16615800
TI  - Automated on-line renewable solid-phase extraction-liquid chromatography
      exploiting multisyringe flow injection-bead injection lab-on-valve analysis.
AB  - In this paper, the third generation of flow injection analysis, also named the
      lab-on-valve (LOV) approach, is proposed for the first time as a front end to
      high-performance liquid chromatography (HPLC) for on-line solid-phase extraction
      (SPE) sample processing by exploiting the bead injection (BI) concept. The
      proposed microanalytical system based on discontinuous programmable flow features
      automated packing (and withdrawal after single use) of a small amount of sorbent
      (<5 mg) into the microconduits of the flow network and quantitative elution of
      sorbed species into a narrow band (150 microL of 95% MeOH). The hyphenation of
      multisyringe flow injection analysis (MSFIA) with BI-LOV prior to HPLC analysis
      is utilized for on-line postextraction treatment to ensure chemical compatibility
      between the eluate medium and the initial HPLC gradient conditions. This
      circumvents the band-broadening effect commonly observed in conventional on-line
      SPE-based sample processors due to the low eluting strength of the mobile phase.
      The potential of the novel MSFI-BI-LOV hyphenation for on-line handling of
      complex environmental and biological samples prior to reversed-phase
      chromatographic separations was assessed for the expeditious determination of
      five acidic pharmaceutical residues (viz., ketoprofen, naproxen, bezafibrate,
      diclofenac, and ibuprofen) and one metabolite (viz., salicylic acid) in surface
      water, urban wastewater, and urine. To this end, the copolymeric divinylbenzene
      co-n-vinylpyrrolidone beads (Oasis HLB) were utilized as renewable sorptive
      entities in the micromachined unit. The automated analytical method features
      relative recovery percentages of >88%, limits of detection within the range 0.02
      0.67 ng mL(-1), and coefficients of variation <11% for the column renewable mode
      and gives rise to a drastic reduction in operation costs ( approximately 25-fold)
      as compared to on-line column switching systems.

PMID- 16615801
TI  - Characterization of protein expression and folding in cell-free systems by maldi
      tof mass spectrometry.
AB  - Recent advances in basic research, medicine, and biotechnology provide great
      motivation for the development of analytical tools to probe the behavior of
      target biomolecules in complex biological environments. Cell-free transcription
      translation systems are an attractive medium for such studies, because they mimic
      several biochemical features of living cells, yet they are much more amenable to
      manipulation and spectroscopic analysis. However, few methods are currently
      available to characterize target proteins in cell-free systems. We have employed
      matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass
      spectrometry for the detection and characterization of two cell-free expressed
      model proteins, cold shock protein A and apomyoglobin (apoMb) in cell-free
      systems. We exploited a combination of multiple selective isotope-labeling
      patterns for the identification of both full-length proteins and their in situ
      generated proteolytic fragments. MALDI-TOF mass spectrometry-detected
      hydrogen/deuterium exchange, performed directly in the cell-free medium, allowed
      the assessment of apoMb's global degree of folding. The above methods are
      straightforward in that they do not require high levels of protein expression and
      allow the efficient characterization of both protein identity and global degree
      of folding.

PMID- 16615802
TI  - Development and application of porous membrane-protected carbon nanotube micro
      solid-phase extraction combined with gas chromatography/mass spectrometry.
AB  - A novel, multiwalled carbon nanotube (MWCNT)-supported micro-solid-phase
      extraction (mu-SPE) procedure has been developed. A 6-mg sample of MWCNTs was
      packed inside a (2 cm x 1.5 cm) sheet of porous polypropylene membrane whose
      edges were heat-sealed to secure the contents. The mu-SPE device, which was
      wetted with dichloromethane, was then placed in a stirred sewage sludge sample
      solution to extract organophosporous pesticides, used here as model compounds.
      Tumbling of the extraction device within the sample solution facilitated
      extraction, and the porous membrane acted as a filter to exclude the extraction
      of extraneous materials. After extraction, analytes were desorbed in hexane and
      analyzed using gas chromatography/mass spectrometry. Since the porous membrane
      afforded protection of the MWCNTs, no further cleanup of the extract was
      required. The pi-pi electrostatic interaction with the analytes and the large
      surface area of MWCNTs facilitated the adsorption of analytes, with good
      selectivity and reproducibility. Under the optimized extraction conditions, the
      method showed good linearity in the range of 0.1-50 mug/L, repeatability of the
      extractions (RSD 2-8%, n = 4), and low limits of detection (1-7 pg/g). No analyte
      carryover effect was observed, and each mu-SPE device could be used for up to 30
      extractions. Comparison was made with hollow fiber protected solid-phase
      microextraction and headspace solid-phase microextraction; mu-SPE was
      demonstrated to be a fast, accurate, and cost-effective pretreatment method for
      sewage sludge samples.

PMID- 16615803
TI  - UV excitation thermal lens microscope for sensitive and nonlabeled detection of
      nonfluorescent molecules.
AB  - An ultrasensitive and nonlabeled detection method of nonfluorescent molecules on
      a microchip was developed by realizing a thermal lens microscope (TLM) with a 266
      nm UV pulsed laser as an excitation light source (UV-TLM). Pulsed laser sources
      have advantages over continuous-wave laser sources in more compact size and
      better wavelength tuning, which are important for microchip-based analytical
      systems. Their disadvantage is difficulty in applying a lock-in amplifier due to
      the high (>10(4)) duty ratio of pulse oscillation. To overcome this problem, we
      realized a quasi-continuous-wave excitation by modulating the pulse trains at
      approximately 1 kHz and detecting the synchronous signal with a lock-in
      amplifier. The optimum pulse repetition frequency was obtained at 80 kHz, which
      was reasonable considering thermal equilibrium time. Furthermore, a permissible
      flow velocity in the range of 6.6-19.8 mm/s was found to avoid sensitivity
      decrease due to photochemical reactions and thermal energy dissipation. Under
      these conditions, we detected adenine aqueous solutions on a fused-silica
      microchip without labeling and obtained a sensitivity that was 350 times higher
      than that in a spectrophotometric method. The sensitivity was enough for
      detection on a microchip with an optical path length that was 2-3 orders shorter
      than that in conventional cuvettes. Finally, the UV-TLM method was applied to
      liquid chromatography detection. Fluorene and pyrene were separated in a
      microcolumn and detected in a capillary (50-microm inner diameter) with 150 times
      higher sensitivity than a spectrophotometric method. Our method provides highly
      sensitive and widely applicable detections for various analytical procedures and
      chemical syntheses on microchips.

PMID- 16615804
TI  - Rare large scale subdomain motions in prion protein can initiate aggregation.
AB  - The prion protein is thought to induce prion diseases by changing its
      conformation from the cellular form, PrP(C), into the infectious Scrapie-form,
      PrP(Sc). Little is known about the structural and dynamical features of this
      conformational change. We here introduce a novel concept that involves rare large
      scale motions between the subdomains beta1-alpha1-beta2 and alpha2-alpha3 in the
      carboxy-terminal, globular part of PrP. The interface between these two
      subdomains carries most pathogenic mutations known to be associated with prion
      diseases. Based on computational simulations as well as experimental results we
      propose that such a large scale motion subsequently destabilizes large parts of
      the cellular conformer PrP(C), thus, rendering it prone to structural
      rearrangements, including aggregation of now partially unfolded parts of the PrP
      sequence. We hypothesize that such large scale motions occur as a rare event even
      under equilibrium conditions and that the interaction of such partially
      destabilized PrP(C)-conformers, which we named PrP(C*), contributes to the
      formation of pathogenic oligomeric species of the prion protein.

PMID- 16615805
TI  - G-specific RNA-cleaving conjugates of short peptides and
      oligodeoxyribonucleotides.
AB  - Artificial ribonucleases, conjugates of short oligodeoxyribonucleotides and
      peptides built of arginine, leucine, proline, and serine, were synthesized and
      assessed in terms of ribonuclease activity and specificity of RNA cleavage. A
      specific group of the conjugates was identified that display T1-ribonuclease-like
      activity and cleave RNA predominantly at G-X sequences. Circular dichroism study
      of the structures of the most active conjugates, free peptide (LR)4G, and
      oligonucleotides revealed that conjugation of oligonucleotide to the peptide
      results in a specific peptide folding that possibly provides ribonuclease
      activity to the conjugate.

PMID- 16615806
TI  - The mechanism of TC23O's thermostability: a molecular dynamics simulation study.
AB  - The quasielastic neutron scattering index beta and the modulus of a protein's
      quasi-electric dipole moment were utilized to quantitate the thermostability of
      wildtype TC23O and its mutants. Charged residues Arg314, Glu246, Glu291, and some
      prolines near the C-terminus of the sequence (Pro228, Pro296, and Pro308) were
      identified to be critical for the thermostability of wildtype TC23O according to
      these two criteria. By analyzing the molecular conformation changes during the
      simulation, it was demonstrated how the mutant P228S was destabilized by
      disrupting two salt-bridges Asp116OD1-Lys215N and Glu210OE1-Lys217N at an
      adjacent beta-turn. The destabilization of P296S also shown to be intimate
      correlated with the break down of ion pair Lys188N-Glu291OE1. The sensitivity of
      its electrostatic network to the local structure is an important feature. It
      reveals that the 'proline effect' and electrostatic interactions together
      influences the thermostability of TC23O a lot.

PMID- 16615807
TI  - Structural and dynamical properties of a full-length HIV-1 integrase: molecular
      dynamics simulations.
AB  - The structural and dynamical properties of the complete full-length structure of
      HIV-1 integrase were investigated using Molecular Dynamics approach. Simulations
      were carried out for the three systems, core domain only (CORE), full-length
      structure without (FULL) and with a Mg2+ (FULL+ION) in its active site, aimed to
      investigate the difference in the molecular properties of the full-length models
      due to their different construction procedures as well as the effects of the two
      ends, C- and N-terminal, on those properties in the core domain. The full-length
      structure was prepared from the two experimental structures of two-domain
      fragment. The following properties were observed to differ significantly from the
      previous reports: (i) relative topology formed by an angle between the three
      domains; (ii) the cavity size defined by the catalytic triad, Asp64, Asp116, and
      Glu152; (iii) distances and solvation of the Mg2+; and (iv) conformation of the
      catalytic residues. In addition, the presence of the two terminal domains
      decreases the mobility of the central core domain significantly.

PMID- 16615808
TI  - Investigation of interaction between enolase and phosphoglycerate mutase using
      molecular dynamics simulation.
AB  - Two glycolytic enzymes, phosphoglycerate mutase (PGM) and enolase from
      Saccharomyces cerevisiae have been chosen to detect complex formation between
      active centers (a/c), using molecular dynamics simulation. Enzymes have been
      separated by 10 A distance and placed in a water box of size 173 x 173 x 173 A.
      Three different orientations where a/c of PGM and enolase were positioned toward
      each other have been used for investigation. The two initial 3-phosphoglycerate
      substrates at near active centers of initial structure of PGM have been replaced
      with final 2-phosphoglycerate products. 150mM of NaCl have been added to the
      system to observe binding activity in the near physiological conditions. Analysis
      of interaction energies and conformation changes for 3ns simulation indicates
      that PGM and enolase do show binding affinity between their near active regions.
      Moreover the similarity between final conformations of the first two orientations
      with the initial conformation of the third orientation suggests that complex
      formation between a/c of enzymes is not confined only by discussed orientations.
      Clear interaction of enolase with C-terminal tail of PGM has been recorded. These
      results suggest that substrate direct transfer mechanism may exist between
      enzymes.

PMID- 16615809
TI  - Amino Acid Principal Component Analysis (AAPCA) and its applications in protein
      structural class prediction.
AB  - The extremely complicated nature of many biological problems makes them bear the
      features of fuzzy sets, such as with vague, imprecise, noisy, ambiguous, or input
      missing information For instance, the current data in classifying protein
      structural classes are typically a fuzzy set To deal with this kind of problem,
      the AAPCA (Amino Acid Principal Component Analysis) approach was introduced. In
      the AAPCA approach the 20-dimensional amino acid composition space is reduced to
      an orthogonal space with fewer dimensions, and the original base functions are
      converted into a set of orthogonal and normalized base functions The advantage of
      such an approach is that it can minimize the random errors and redundant
      information in protein dataset through a principal component selection,
      remarkably improving the success rates in predicting protein structural classes
      It is anticipated that the AAPCA approach can be used to deal with many other
      classification problems in proteins as well.

PMID- 16615810
TI  - Conformations of higher gangliosides and their binding with cholera toxin -
      investigation by molecular modeling, molecular mechanics, and molecular dynamics.
AB  - Molecular mechanics and molecular dynamics studies are performed to investigate
      the conformational preference of cell surface higher gangliosides (GT1A and GT1B)
      and their interaction with Cholera Toxin. The water mediated hydrogen bonding
      network exists between sugar residues in gangliosides. An integrated molecular
      modeling, molecular mechanics, and molecular dynamics calculation of cholera
      toxin complexed with GT1A and GT1B reveal that, the active site of cholera toxin
      can accommodate these higher gangliosides. Direct and water mediated hydrogen
      bonding interactions stabilize these binding modes and play an essential role in
      defining the order of specificity for different higher ganglioside towards
      cholera toxin. This study identifies that the binding site of cholera toxin is
      shallow and can accommodate a maximum of two NeuNAc residues. The NeuNAc binding
      site of cholera toxin may be crucial for the design of inhibitors that can
      prevent the infection of cholera.

PMID- 16615811
TI  - Design and evaluation of single-stranded DNA carrier molecules for DNA-directed
      assembly.
AB  - Due to the exceptional molecular recognition properties of nucleic acids, the
      computational design of DNA sequence motifs is of paramount interest for a wide
      variety of applications, ranging from DNA-based nanotechnology and DNA computing
      to the broad field of DNA microarray technologies. These applications rely on the
      specificity of Watson-Crick base-pairing, and thus, are highly sensitive to non
      specific interactions and the formation of any undesired secondary structures,
      which contradict an efficient intermolecular hybridization. Here we report on the
      in silico design and in vitro evaluation of single-stranded DNA (ssDNA) carrier
      strands for the directional DNA-based positioning of streptavidin (STV)
      conjugates covalently tagged with short ssDNA oligonucleotides. Each such carrier
      strand consists of four hybridization sites complementary to the conjugate DNA
      strands. The high and homogeneous hybridization efficiency measured in vitro by
      microarray hybridization assays confirms the quality of our in silico sequence
      design method. Hybridization efficiency of DNA-STV-conjugates depends on the
      position of the hybridization site in the carrier sequence, where the positions
      nearest to and farthest from the microarray surface proved to be most favorable.

PMID- 16615812
TI  - Specific interactions of divalent metal ions with a DNA duplex containing the
      d(CA)n/(GT)n tandem repeat.
AB  - Divalent metal ions are essential for maintaining functional states of the DNA
      molecule. Their participation in DNA structure is modulated by the base sequence
      and varies depending on the nature of the ion. The present investigation
      addresses the interaction of Ca2+ ions with a tandem repeat of two CA
      dinucleotides, (CA)2/(TG)2. The binding of Ca2+ to the repeat is monitored by
      nuclear magnetic resonance (NMR) spectroscopy using chemical shift mapping.
      Parallel experiments monitor binding of Mg2+ ions to the repeat as well as
      binding of each ion to a DNA duplex in which the (CA)2/(TG)2 repeat is
      eliminated. The results reveal that the direction and the magnitude of chemical
      shift changes induced by Ca2+ ions in the NMR spectra of the repeat are different
      from those induced by Mg2+ ions. The differences between the two cations are
      significantly diminished by the elimination of the (CA)2/(TG)2 repeat. These
      findings suggest a specific interaction of Ca2+ ions with the (CA)2/(TG)2 motif.
      The specificity of the interaction resides in the two A-T base pairs of the
      repeat, and it involves the major groove of the first A-T base pair and both
      grooves of the second A-T base pair.

PMID- 16615813
TI  - Mid-infrared study of deoxycytidine at high pressures: evidence of a phase
      transition.
AB  - Room temperature mid-infrared experiments between 600 and 1600 cm(-1) have been
      performed on crystalline deoxycytidine as a function of pressure up to about 10
      GPa. The wavenumbers of most vibrational modes shift to higher values with
      increasing pressures except for a mode near 840 cm(-1). Assignments for the
      observed modes are made on the basis of work published in the literature. Several
      anomalies are noted near 4.7 GPa, suggesting a phase transition. Our results for
      deoxycytidine are compared to similar measurements on cytidine.

PMID- 16615820
TI  - Viral load, CD4+ T-lymphocyte counts and antibody titres in HIV-1 infected
      untreated children in Kenya; implication for immunodeficiency and AIDS
      progression.
AB  - BACKGROUND: There are limited reports on HIV-1 RNA load, CD4+ T-lymphocytes and
      antibody responses in relation to disease progression in HIV-1 infected untreated
      children in Africa. METHODS: To describe the relationships between these
      parameters, we conducted a longitudinal cohort study involving 51 perinatally HIV
      1 infected children aged between 1 and 13 years. HIV status was determined by
      ELISA and confirmed by western blot and PCR. Antibodies were quantified by
      limiting dilution ELISA, plasma HIV-1 RNA load by RT-PCR and CD4+ T-lymphocytes
      by FACSCount. RESULTS: Asymptomatic and symptomatic disease had, respectively, a
      rise in median HIV-1 RNA load from 1,195 to 132,543 and from 42,962 to 1,109,281
      copies/ml in children below 6 years. The increase in viral load was 10-fold
      higher for asymptomatic compared to other categories and 2-fold faster for
      children less than 6 years than those above. Similarly, symptomatic children
      below 6 years had initial median CD4+ T-lymphocyte counts of 647 (22%) cells/muL,
      declining to 378 (20%) while those above 6 years had initial values of below 335
      (15%) but which increased to 428 (17%). Median viral load correlated
      significantly with median CD4+ T-lymphocyte percentage in children above 6 years
      (p=0.026) but not below. CONCLUSIONS: Viral load is lower in older than younger
      children and correlates significantly with percentage CD4+ T-lymphocytes.
      Survival by HIV-1 infected children requires a competent immune response early in
      infection to counter the rapidly replicating virus. Interventions aimed at
      boosting the naive immune system may prolong survival in these children.

PMID- 16615821
TI  - Burden of alcohol use in the Uganda Police in Kampala District.
AB  - BACKGROUND: Alcohol dependence is one of the leading causes of the global burden
      of disease. Among members of the Uganda Police Force, alcohol dependence has been
      a major contributor of poor mental health, poor work output and forced
      retirement. OBJECTIVE: This study was carried out to determine the prevalence of
      alcohol dependence and associated psychosocial problems in the Uganda Police
      Force in Kampala District. METHODS OF STUDY: A sample of police officers selected
      by systematic sampling strategy from two large barracks in Kampala District
      participated. A semi-structured questionnaire designed to elicit information on
      the perceived impact of alcohol use was used. Prevalence rate was derived from
      ICD-10 criteria for alcohol dependence, and psychosocial problems in alcohol
      dependence. RESULTS: Twenty respondents (19.2%) met criteria for alcohol use
      disorder, 26.0% met criteria for alcohol use problems and 9.6% reported that
      their health was poor. Alcohol use disorder or problems were significantly
      associated with lack of job satisfaction, poor health, problems in implementing
      personal plans, disciplinary problems, inability to save from personal earnings,
      debts, and absenteeism from work. CONCLUSION: One in five police officers met
      criteria for alcohol use disorder while one in four experienced psychosocial
      problems related to alcohol use. The results suggest serious implications for the
      quality of services provided by the Uganda Police. There is a need to establish
      measures to provide services for those affected, and a further need to establish
      preventative measures against alcohol dependence in the police force.

PMID- 16615822
TI  - Condom and sexual abstinence talk in the Malawi National Assembly.
AB  - BACKGROUND: Correct and consistent use of condoms has been reported as effective
      in the prevention of transmission of HIV. There have been many studies reporting
      on attitudes (perceptions) of communities on condoms and other aspects of HIV and
      AIDS and yet there is paucity of data on the perception towards condoms and
      abstinence by law makers. OBJECTIVE: To determine perceptions of Members of
      Parliament in Malawi towards condoms. METHODS: A qualitative study utilising
      parliamentary Hansards to describe the discussions about condoms and abstinence
      in the National Assembly 1999-2004. Content and discourse analyses were used.
      RESULTS: In general, Members of Parliament had negative attitudes towards extra-
      and/or pre-marital sexual intercourse, condom promotion and use. Sexual
      abstinence amongst non-married persons was preferred as opposed to condom use.
      Condom use was not perceived as an effective way of controlling the spread of
      HIV. Some MPs though called for a change in mind-set so as to allow use of
      condoms in prisons, in order to prevent transmission of infection from prisoners
      to the general community once the prisoners were released. CONCLUSION: This study
      confirms that health interventions such as condoms are not perceived neutrally
      and may be construed as the enemy of society.

PMID- 16615823
TI  - Studies of anticancer and antipyretic activity of Bidens pilosa whole plant.
AB  - Screening of different extracts and fractions from the plant Bidens pilosa Linn.
      var. (Asteraceae) has been conducted using the in-vitro comet assay for
      anticancer and the antipyretic action, which was done with in-vivo models. The
      extract from whole plant was extracted with n-hexane, chloroform and methanol
      extract (E1 - E3). The extracts were fractioned by column chromatography method
      and fractioned with ethyl acetate, acetone and water (F1 - F3). All the extracts
      and fractions were tested for anticancer and antipyretic activity. Among extracts
      E1 shows remarkable anticancer activity and E3 bears maximum antipyretic
      activity. In the antipyretic activity, paracetamol was used as the standard test
      drug. The most promising material (LC50 < 1500 microg/ml) was F1 ethyl acetate
      fractions of methanolic extract and methanolic crude extract of whole plants.
      However, little correlation was observed in the degree of antipyretic activity
      between the test drug and standard drug. In conclusion, the extract obtained from
      the whole plant of Bidens pilosa showed a significant cytotoxic effect to
      methanolic extract against Hela cells by in vitro method and showed a comparable
      antipyretic activity effect to paracetamol in rabbit pyrogen test.

PMID- 16615824
TI  - The in-vitro antibacterial activity of Annona senegalensis, Securidacca
      longipendiculata and Steganotaenia araliacea - Ugandan medicinal plants.
AB  - BACKGROUND: Nearly all cultures from ancient times to the present day have used
      plants as a source of medicines. As a result, different remedies tended to
      develop in different parts of the world. Current strategies to overcome the
      global problem of antimicrobial resistance include research in finding new and
      innovative antimicrobials from plants. OBJECTIVES: To determine the antibacterial
      activity of extracts of Annona senegalensis, Securidacca longipendiculata and
      Steganotaenia araliacea, plants which are used in Eastern Uganda for the
      treatment of diarrhea and wound infections. METHODS: The root barks of these
      plants were collected, sun-dried, pounded using pestles and wooden mortars. Water
      and methanol extracts were derived and screened. Standard cultures of E. coli
      ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Staphylococcus aureus ATCC
      25923 were used in the study. The antibacterial tests used were the agar well
      diffusion assays. The minimum inhibitory concentrations (MIC) were determined by
      cylinder plate technique. RESULTS: Extracts of Annona senegalensis, Steganotaenia
      araliacea and Securidaca longipendiculata showed activity against Staphylococcus
      aureus. The methanol extract of Securidaca longipediculata was not inhibitory to
      S.aureus. Steganotaenia araliacea and Securidaca longipediculata (water) extracts
      were active against all the bacteria tested. The water and methanol extracts of
      Annona senegalensis did not show inhibitory activity against E. coli. Of the
      three bacteria studied, Staphylococcus aureus was the most susceptible to the
      extracts followed by P. aeruginosa. E. coli was least sensitive to the plant
      extracts. Annona senegalensis had the lowest MIC against Staphylococcus aureus
      (62.5 mg/ml); while Steganotaenia araliacea had the highest MIC (250 mg/ml)
      signifying lower activity. CONCLUSIONS: The root bark extracts of the three
      plants showed antibacterial activity, justifying their continued use in treatment
      of bacterial infections. RECOMMENDATIONS: Further studies are required to isolate
      and characterise the active phytochemical constituents in the plants. Toxicity
      studies should be done to determine their safety.

PMID- 16615825
TI  - Mob justice in Tanzania: a medico-social problem.
AB  - OBJECTIVE: To investigate the magnitude of mob justice and associated factors.
      BACKGROUND: Mob justice is a social and public health problem that has grown in
      Tanzania in recent decades that has negative effects on social and health of the
      country, communities, and families. MATERIALS AND METHODS: A four-year autopsy
      study was conducted at the Department of Pathology, MUCHS. Information on the
      cases was obtained from police, the relatives, friends and other witnesses if
      available. RESULTS: 1,249 persons were killed by mobs in Dar es Salaam during the
      period of 5 years (2000-2004). The alleged offense ranged from a serious crime
      like theft or murder to a mere violation of local customs or religious beliefs.
      The mode of the killings were mostly burning (48.11%) and stoning (49.96%). Other
      modes accounted for only 3.0% of the cases. The pattern of injuries ranged from
      skull and other skeletal fractures to viscera rupture. CONCLUSION: MJ is a
      social, legal and public health problem in Tanzania that needs immediate
      attention. Unemployment of youth and perceived economic inequalities should be
      addressed. As long as the judicial system doesn't work and corruption is not
      punished, people will continue to organize their own trials and judge their
      suspects in the street. These must be tackled in order to reduce the growing
      incidences of mob justice, hence saving life. It must be ensured that criminals
      do not violate the freedom, dignity and respect of each and every human or member
      of the society.

PMID- 16615826
TI  - Upper gastrointestinal endoscopic findings in adolescents at Lacor Hospital,
      Uganda.
AB  - BACKGROUND AND OBJECTIVES: Fiberoptic endoscopy is a highly efficient diagnostic
      tool, which is now being increasingly used, in the pediatric age group. This
      study has been carried out to demonstrate indications for and common findings of
      endoscopy in children. MATERIALS AND METHODS: We retrospectively reviewed the
      medical records for endoscopy indication and result of children who had endoscopy
      between Jan 2000 to June 2005. RESULTS: We analyzed 135 children who were
      referred for upper gastrointestinal endoscopy. There were 38 boys and 97 girls.
      The mean age was 16 years (SD+/-1.4293). The main indications comprised
      epigastric pain (67.4%), dyspepsia (11.9), hematemesis (8.9%), recurrent
      abdominal pain (3%) recurrent vomiting (3%), and miscellaneous (5.8%). Endoscopic
      diagnose included duodenal ulcer (14.8%) and gastritis (12.6%); duodenal scarring
      (5.2%), bile reflux (5.2%) duodenitis (4.4%) and miscellaneous 6.4%. CONCLUSION:
      In Upper gastrointestinal endoscopy is a diagnostic procedure in children with
      gastrointestinal disorder. Gastritis and duodenal disease are commonly seen in
      children, hence must be included in differential diagnosis of children with
      digestive complaints and its management.

PMID- 16615827
TI  - Storage of antimalarials at household level and associated factors in Kiromo
      ward, Bagamoyo Tanzania.
AB  - BACKGROUND: Malaria is a highly debilitating and frequently fatal disease of wide
      distribution. Improper drug storage and rampant self-medication are some of the
      factors that may contribute to an increase in the development of drug resistance
      by malaria parasites towards antimalarials. OBJECTIVES: To determine the extent
      of antimalarial drugs storage, sources and associated factors at household level
      at Kiromo ward in Bagamoyo, Coast region, Tanzania after the introduction of SP
      replacing chloroquine as first line. METHODS: A total of 300 households from
      three villages making up Kiromo ward were included in this study. Swahili version
      of the questionnaire and a checklist were used in data collection. RESULTS: Of
      the 300 households visited 25 (8.3%) were found to store antimalarials. The most
      commonly stored antimalarials were amodiaquine (30.8%) and quinine (34.6%). Most
      of these were in tablet form (76.9%). The source of these drugs was mostly from
      dispensaries. Kiromo was the only dispensary in the ward and others were outside
      the ward. These drugs were stored in special containers for safety. Frequent
      episodes of illness in the family were given as the most (56%) common reasons for
      drug storage in the families, followed by distance (20%). There was a
      statistically significant (p<0.05) association between storage of antimalarial
      drugs and number of children in the family and presence of a family member with
      febrile illness. The study further showed that out of 26 different types of
      antimalarials stored, only 7 (26.9%) had expiry dates on the containers because
      these were original containers of the drugs. CONCLUSION: The study revealed that
      few households store antimalarial drugs with amodiaquine and quinine being the
      most stored. The majority of the households obtained antimalarial drugs from
      dispensaries. Health education should be given not only to the patients but also
      the entire general public on the appropriate drug use, safety, expiry dates and
      appropriate storage. A model dispensary like Kiromo should be implemented in
      other rural areas.

PMID- 16615828
TI  - A review of diagnosis and modes of presentation of tropical idiopathic lower limb
      gangrene.
AB  - BACKGROUND: Tropical idiopathic lower limb gangrene (TILLG) is also known as
      Symmetrical gangrene in the African, Idiopathic gangrene in the African and
      Idiopathic peripheral gangrene of the tropics. The aetiopathogenesis of this
      clinical entity is a mystery. OBJECTIVE: To review methods of diagnosing tropical
      idiopathic lower limb gangrene (TILLG) and highlight its clinical variants.
      METHOD: All Literature on idiopathic gangrene of the extremities was searched
      from libraries, colleagues and internet but only literature on TILLG (in
      Africans) from 1947 to date was scrutinised. Each case was studied to find out
      the basis of diagnosis. RESULT: TILLG is not fully understood and not easy to
      recognise. Two sets of criteria are known to be helpful in establishing
      diagnosis. These criteria can be classified as major and minor criteria. Major
      criteria are those clinical data that can establish the diagnosis of TILLG. No
      devices are required to identify them. Minor criteria are pathological changes
      that are consistent with TILLG. Devices are required to identify them. Three
      pathomorphological types of TILLG were described in literature and are classified
      as types A, B and C. CONCLUSIONS: This review is supposed to sensitise the
      clinician and make diagnosis easier. This will also encourage more researches. As
      more information becomes available, aetiopathogenesis of TILLG will be clearer
      and more clinical variants of the disease may be reported. This additional
      information will help in the prevention of gangrene, reducing the socioeconomic
      problems arising from amputation.

PMID- 16615829
TI  - Fetal hemoglobin during infancy and in sickle cell adults.
AB  - BACKGROUND: Fetal hemoglobin has been implicated in the modulation of sickle cell
      crisis though it is functional during infancy. OBJECTIVE: The purpose of this
      study was to determine the waning time of fetal hemoglobin (HbF) and its
      persistence in later life. METHOD: Ninety infants aged 0-12 months, admitted at
      hospital, were tested for their HbF levels. Adult patients numbering 690 were
      also examined for their sickle cell status and a sickle positive patient of SS
      type with HbF had her family members recruited and their sickle cell types
      determined. RESULTS: The results revealed that HbF was highest (98%) at birth,
      decreasing at 5% per week till 6 months when it wane off. Ten infants aged 6-12
      months had HbF persisting at a level of 10% or more. Adult patients examined
      showed proportions of their sickle cell types as AS forming 51%, AC 20%, SS 19%,
      and SC 10%. An SS adult patient with mild sickle cell crisis had an ASF father
      who had no crisis and a mother and brother with AS each who had severe crisis.
      CONCLUSION: These findings suggest that HbF wanes off during infancy but persist
      in some adults and may modulate crisis in these adults. This has implications in
      sickle cell management.

PMID- 16615830
TI  - Neurologic infections in a Nigerian university teaching hospital.
AB  - BACKGROUND: Neurologic infections are an important cause of morbidity and
      mortality especially worldwide but much more in the African continent. The
      frequency of the different types of neurologic infections and their mortality in
      this part of Nigeria is not known. OBJECTIVES: To review cases admitted into the
      main tertiary referral center in Rivers State of Nigeria with neurologic
      infections over a 10-year period and to determine the types of infections, their
      frequency and the mortality. METHODS: Case notes of all admissions into the
      medical wards of UPTH, Port Harcourt between April 1993 and March 2003 were
      reviewed. Cases admitted with neurologic infections were extracted and analyzed
      for the study. RESULTS: Of the 1,395 patients admitted with neurologic disorders
      during the study period, 311 (22.3%) had neurological infections. The M:F ratio
      and mean age of patients with neurologic infections were 1.7:1 and 34.1 years
      respectively. The most common infections identified were meningitis 136(43.7%),
      tetanus 90(28.9%), Pott's disease with cord compression 30(9.6%), viral
      meningoencephalitis 27(8.7%) and tuberculous meningitis (TBM) 19(6.1%). The case
      fatality was high: meningitis 49.3%, tetanus 47.8%, Pott's disease 23.3%,
      meningoencephalitis 44.4% and TBM 68.4%. CONCLUSIONS: Preventable neurologic
      infections are a very important cause of morbidity and mortality in this
      environment. Cases presenting with suspicious neurologic infections should be
      referred to centers where specialized care can be instituted.

PMID- 16615831
TI  - Characterization and management of solid medical wastes in the Federal Capital
      Territory, Abuja Nigeria.
AB  - BACKGROUND: Medical establishment such as hospitals and research institutes
      generate sizable amount of hazardous waste. Health care workers, patients are at
      risk of acquiring infection from sharps and contamination of environment with
      multiple drug resistant microorganisms if wastes are not properly managed.
      OBJECTIVES: To characterize types and evaluate waste disposal techniques employed
      in the management of solid medical wastes in five selected hospitals in the
      Federal Capital Territory, Abuja. METHODS: This was a cross section study
      involving the use of questionnaires, in-depth interview, meetings, discussions
      and participant observed strategy. It also involved the collection, sorting
      (segregation), identification and characterization and weighing of waste types
      from wards and units in the selected hospitals. RESULTS: The average waste
      generation rate per bed/day was determined and found to be 2.78 kg of solid
      waste, 26.5% of the total waste was hazardous in nature. Waste segregation was
      found not to be practiced by any of the hospitals surveyed, 18.3% of the
      hospitals incinerated waste in a locally built brick incinerator; 9.1% bury;
      36.3% burn waste in open pits while 36.3% dispose of a waste into municipal
      dumpsites. CONCLUSION: Waste management officers do not have formal training in
      waste management techniques; and hospital administrators pay very little
      attention to appropriate management of medical waste. Therefore, we must educate
      waste generators of their responsibility to properly manage the waste so that
      their staff, patients, environment and community is protected.

PMID- 16615832
TI  - Focusing on environmental aspect of HIV/AIDS prevalence in Abuja - Nigeria.

PMID- 16615835
TI  - Gender equity and reproductive health.

PMID- 16615836
TI  - Risk factors for severe abruptio placenta in Mulago Hospital, Kampala, Uganda.
AB  - OBJECTIVE: To determine the risk factors for severe abruptio placenta in Mulago
      hospital, Kampala, Uganda. DESIGN: A case control study. SETTING: Mulago hospital
      labour wards Study population: Women who delivered in Mulago hospital.
      PARTICIPANTS: Forty five women with severe abruptio placenta (cases) were
      recruited between 15(th) November 2001 and 30(th) November 2002. They were
      followed up and compared to five hundred women (controls) who had normal
      deliveries. OUTCOME VARIABLES: Socio-demographic characteristics, familial
      history, medical history, gynaecological and obstetric history. RESULTS: The risk
      factors for severe abruptio placenta were low socio economic status (OR 10.5,95%
      CI 3.8 to 29.2), co existing hypertension (OR 56.8, 95% CI 9.0 to 358.5),
      previous history of stillbirth (OR 3.1,95% CI 1.1 to 9.1), delivery by caesarean
      section in previous pregnancy (OR 7.3, 95% CI 1.8 to 29.7), non attendance of
      antenatal care(OR 6.5, 95% CI 2.0 to 21.2), recurrent vaginal bleeding(OR 26.7,
      95% CI 8.6 to 85.4) and delivery of male babies(OR 2.2, 95% CI: 1.2 to 4.9).
      CONCLUSION: The risk factors for abruptio placenta were chronic hypertension,
      recurrent vaginal bleeding, previous delivery with caesarean section and low
      socio economic status. These factors can be identified during prenatal period and
      used to prevent maternal morbidity and mortality.

PMID- 16615837
TI  - Papillary squamous cell carcinoma of the cervix in Uganda: a report of 20 cases.
AB  - BACKGROUND: Non-glandular papillary carcinoma of the cervix are uncommon tumours.
      In Uganda where cervical carcinoma is very common, no cases of papillary squamous
      cell carcinoma of the cervix has been reported. OBJECTIVES: To ascertain the
      occurrence and describe the clinicopathological features of papillary squamous
      cell carcinoma of the cervix in Uganda. STUDY DESIGN: Retrospective review of
      histologically diagnosed cases of squamous cell carcinoma of cervix with
      papillary structures. METHODS: Retrospective review of cases of cervical
      carcinoma diagnosed in the Pathology Department, Makerere University from 1968 to
      1973 was done. Cases with features of squamous differentiation and forming
      papillary pattern were then selected. RESULTS: Twenty cases were encountered and
      the ages of the patients ranged from 22 to 70 years (mean 46.6 years).
      Histologically, the tumours had thin to broad fibrovascular cores covered by
      multilayered squamous epithelium. In five cases, there were areas with very
      delicate fibrovascular cores covered by monolayered epithelial cells. CONCLUSION:
      The results of this study show that in Uganda, papillary squamous cell carcinoma
      of the cervix does occur and is predominantly a disease of older women. The
      results also confirm that papillary squamous cell carcinoma is a distinct subtype
      with some variants, and support the hypothesis that squamous cell carcinoma of
      the cervix is heterogeneous group of tumuors.

PMID- 16615838
TI  - Anaemia in pregnancy: a survey of pregnant women in Abeokuta, Nigeria.
AB  - BACKGROUND: Anaemia in pregnancy is a common problem in most developing countries
      and a major cause of morbidity and mortality especially in malaria endemic areas.
      In pregnancy, anaemia has a significant impact on the health of the foetus as
      well as that of the mother. 20% of maternal deaths in Africa have been attributed
      to anaemia. OBJECTIVES AND METHODS: This study was therefore carried out to
      determine the prevalence of anaemia among pregnant women receiving antenatal care
      in two hospitals and a traditional birth home in order to obtain a broader
      prevalence data. Pregnant women were enrolled in the study at their first
      antenatal visit and were monitored through pregnancy for anaemia. Packed cell
      volume (PCV) was used to assess level of anaemia; Questionnaires were also
      administered to obtain demographic information. RESULTS: Three hundred and sixty
      five (76.5%) of the women were anaemic at one trimester of pregnancy or another.
      Anaemia were more prevalent among primigravidae (80.6%) than the
      multigravidae(74.5%)(P>0.05). Two hundred and eleven women (57.8%) had moderate
      anaemia while 147 (40.3%) had mild anaemia and 7(1.9%) were severely anaemic (5
      (71.4%) of which were primigravidae). All severely anaemic women were under 30
      years old. Women attending TBH for antenatal care were found to be more anaemic
      (81.2%) (Even at various trimesters of pregnancy) than those attending the
      hospitals (72.5%) (P<0.05). However, in all the antenatal centers more women were
      anaemic in the 2(nd) trimester of pregnancy. Forty-seven (9.8%) of the enrolled
      women booked for antenatal care in the first trimester, while 303(63.5%) booked
      in the second trimester and 127(26.6%) in the 3(rd) trimester of their
      pregnancies. 62.5% of these women were already anaemic at the time of antenatal
      booking, with a higher prevalence among the primigravidae (69.7%)(P < 0.05).
      Absence of symptoms of ill health was the major reason for late antenatal
      booking. Anaemia was higher among unemployed women and those with sickle cell
      traits. CONCLUSION: Educating women on early antenatal booking and including
      those in TBHs in health interventions is necessary to reduce the problem of
      anaemia in pregnancy in Nigeria.

PMID- 16615839
TI  - Implications of bride price on domestic violence and reproductive health in
      Wakiso District, Uganda.
AB  - OBJECTIVE: Bride price payment is a gender issue with implications on gender
      relations in different socio-cultural contexts. It also impacts Sexual and
      Reproductive Health and Rights. In a qualitative study on the perceptions of
      domestic violence in Wakiso district, payment of bride price emerged as one of
      the key factors associated with domestic violence. The study explored
      experiences, motivations, meanings, consequences and reproductive health
      implications of bride price payment in Wakiso district Uganda. METHODS: 10 single
      sex focus group discussions and 14 in-depth interviews were conducted in Wakiso
      and Nangabo sub-counties, Wakiso district from July 2003 through March 2004. Data
      was analyzed by thematic content analysis, assisted by Easy Text software for
      data retrieval. FINDINGS: Participants perceived bride price as indicating that a
      woman was 'bought' into the man's household, which reduced her household decision
      making roles. It limited women's independence and perpetuated unequal gender
      power relations, especially regarding health-seeking behaviour. CONCLUSION: Bride
      price payment is a contextual factor that the community in Wakiso District,
      Uganda, perceived as associated with domestic violence, with serious sexual and
      reproductive health implications.

PMID- 16615840
TI  - Experiences of pregnant adolescents--voices from Wakiso district, Uganda.
AB  - BACKGROUND: In Uganda, morbidity and mortality among adolescent mothers and their
      children are high. Social factors behind this problem need to be better
      understood. OBJECTIVE: To explore problems that pregnant adolescents face in
      order to design appropriate policies and interventions. METHODS: This was a
      descriptive study that utilized qualitative methods for data collection. The
      study population comprised of pregnant adolescents, adolescent mothers, opinion
      leaders, In-charge of health unit, and Traditional Birth Attendants (TBAs) in
      Wakiso district, Uganda. Six Focus Group Discussions (FGDs) with adolescent
      mothers and pregnant adolescents, and six key informant interviews were conducted
      with leaders in-charge of health units and TBAs. A moderator and a note taker
      facilitated the FGDs, which were tape recorded with consent from participants.
      Qualitative content analysis was done. RESULTS: Discussions revealed that
      pregnant adolescents faced domestic physical violence. Furthermore, they were
      psychologically violated by parents and partners, and the community within which
      they lived. Pregnant adolescents were treated inhumanely and overworked with
      household chores and had inadequate food to eat. Adolescents experienced stigma
      and as a result some had carried out unsafe abortions. Key informant interviews
      and FGDs revealed that health workers were rude and unsympathetic to pregnant
      adolescents. This significantly contributed to delayed health care seeking when
      adolescents were ill. CONCLUSION: Pregnant adolescents lack basic needs like
      shelter, food and security. They also face relational problems with families,
      partners and the community. There is, therefore, a need to sensitize the
      community and school personnel about adolescent reproductive health issues. In
      addition, adolescent friendly services need to be established/strengthened.
      Continuous in-service training for health workers with emphasis on counseling
      skills for young people is urgently needed.

PMID- 16615841
TI  - Prolonged displacement may compromise resilience in Eritrean mothers.
AB  - OBJECTIVE: to assess the impact of prolonged displacement on the resilience of
      Eritrean mothers. METHODS: an adapted SOC scale (short form) was administered.
      Complementary qualitative data were gathered from study participants' spontaneous
      reactions to and commentaries on the SOC scale. RESULTS: Displaced women's SOC
      scores were significantly less than those of the non-displaced: Mean = 54.84; SD
      = 6.48 in internally displaced person (IDP) camps, compared to non-displaced
      urban and rural/pastoralist: Mean = 48. 94, SD = 11.99; t = 3.831, p < .001. Post
      hoc tests revealed that the main difference is between IDP camp dwellers and
      urban (non-displaced). Rural but traditionally mobile (pastoralist or
      transhumant) communities scored more or less the same as the urban non-displaced-
      i.e., significantly higher than those in IDP camps (p < 0.05). Analysis of
      variance confirmed that gender is critical: displacement has significantly
      negative effects on women compared to men: RR = .262, p < .001. SOC scores of
      urban and pastoralist/transhumant groups were similar, while women in IDP camps
      were lower scoring--RR = .268, p < .001. CONCLUSIONS: The implications of these
      findings for health policy are critical. It is incumbent on the international
      health institutions including the World Health Organization and regional as well
      as local players to address the plight of internally displaced women, their
      families and communities in Eritrea and other places of dire conditions such as,
      for example Darfur in the Sudan.

PMID- 16615842
TI  - Perceptions of health care providers in Mulago hospital on prevention and
      management of domestic violence.
AB  - OBJECTIVE: To explore knowledge, attitudes and practices of health workers in
      Mulago hospital towards domestic violence prevention and management, especially
      violence during pregnancy. METHODS: From 5(th) to 25(th) March 2000, self
      administered pre-coded questionnaires were given to a purposively selected sample
      of 48 health workers identified from staff of the Obstetrics and Gynaecology
      department, Mulago hospital, Uganda. The questionnaire had 22 statements
      assessing knowledge, attitudes and practices, to which participants gave
      responses on a Likert scale ranging from whether they agreed, disagreed or were
      undecided. Responses were analyzed in terms of frequencies and percentages. To
      corroborate information obtained, in-depth interviews were conducted with clinic
      and ward administrators on knowledge, attitudes, practices and barriers to
      survivors' management. RESULTS: Many respondents had poor knowledge of domestic
      violence management or prevention. Though they believed counseling survivors was
      necessary, none of the in-depth interviewees had counseling skills or had ever
      referred patients or survivors for such counseling. Lack of technical competence,
      negative attitudes and institutional constraints were cited as main barriers to
      provision of optimal care to survivors. CONCLUSION: Health workers of Mulago
      hospital lacked knowledge on management, had negative attitudes and provided sub
      optimal care to domestic violence survivors.

PMID- 16615843
TI  - Competence of maternal and child health clinic workers in detecting malnutrition
      in Somalia.
AB  - BACKGROUND: The MCH clinic workers in Somalia receive formal and in-service
      training to perform their professional duties. Their competence in the field was
      never examined. This study assessed their competencies in detecting malnourished
      children 5 years and below in Beledweyne. OBJECTIVE: To assess the competence of
      MCH clinic workers in detecting malnourished children. DESIGN: Cross-sectional
      study. METHODS: The study was conducted in 1989. We obtained data on children
      five years and below from the MCH clinic in Beledweyne, Somalia. We analyzed two
      months data. We used CASP program to calculate the Weight-for-Age index (WFA).
      The nutritional status determined by the MCH clinic workers and the WFA index
      were used to estimate the positive and negative predicted values of the MCH
      clinic workers' competence in detecting malnourished children. RESULTS: We
      studied 487 children 5 years old and below. The health workers determined that
      13.5% were malnourished. The positive and negative predicted values of the MCH
      clinic workers' nutritional measure were 76% and 92% respectively. CONCLUSION:
      The MCH clinic workers showed deficiency in their competence to detect
      malnourished children. They misclassified 10% of the children, which was worse
      among the malnourished, due to incorrect plotting of the child's current weight
      on the growth chart.

PMID- 16615844
TI  - Mother's health seeking behaviour during child illness in a rural western Kenya
      community.
AB  - BACKGROUND: In most developing countries, the health of the children is strongly
      dependant on maternal healthcare behaviour. The study describes the prevalence of
      illness among preschool children in a rural sugarcane growing community and the
      mother's health seeking behavior. OBJECTIVES: To document the presence of illness
      among preschool children at household level in a rural community in Western Kenya
      and also determine the mother's health seeking behavior during the course of
      these illnesses. METHODS: This was an observational cross-sectional community
      survey using interview schedules, key informants and focus group discussions and
      Makunga Rural Health Center in Kakamega District western Kenya. Descriptive
      statistics were used in data analysis. RESULTS: Fifty two percent of the children
      had had at least one illness a week prior to the survey. Fever was the most
      commonly reported symptom with 48% of the cases. A third (32.4%) of the mothers
      purchased and administered drugs to their sick children without seeking medical
      attention. The most commonly reported reasons for this behavior were: the
      government health facilities were at a distance, the services are poor and
      inability to afford services at the private hospitals and clinics. CONCLUSION:
      Intervention programmes focusing on diversification of income sources, maternal
      education and community based mobile clinics are likely to contribute towards
      improved health of children in this and any other rural sugarcane growing
      community.

PMID- 16615845
TI  - The pervasive triad of food security, gender inequity and women's health:
      exploratory research from sub-Saharan Africa.
AB  - OBJECTIVES: This study was designed to explore the interactions between food
      securing activities, health and gender equity from the perspective of rural east
      African women. The specific objectives were to document the critical interaction
      among these three issues-food security, gender inequity, women's health within
      the context of sub-Saharan Africa; to describe the nature of this triad from the
      perspective of women farmers in Africa; and to propose a framework for linking
      available interventions to the vicious nature of this triad. SETTING: In-depth
      interviews and focus group discussions were conducted with rural women farmers in
      Kwale District, Kenya and Bagamoyo District, Tanzania. METHODS: A total of 12 in
      depth interviews and 4 focus group discussions have been included in this
      analysis. Transcribed text from interviews and focus group discussions were coded
      and thematic conceptual matrices were developed to compare dimensions of common
      themes across interviews and settings. A thematic analysis was then performed and
      a framework developed to understand the nature of the triad and explore the
      potential for interventions within the interactions. FINDINGS: The vicious cycle
      of increasing work, lack of time, and lack of independent decision making for
      women who are responsible for food production and health of their families, has
      health and social consequences. Food securing activities have negative health
      consequences for women, which are further augmented by issues of gender inequity.
      CONCLUSION: The African development community must respond by thinking of
      creative solutions and appropriate interventions for the empowerment of women
      farmers in the region to ensure their health.

PMID- 16615846
TI  - Under-reporting of gravidity in a rural Malawian population.
AB  - BACKGROUND: Mis-reporting of data by study participants in a questionnaire-based
      study is an important source of bias in studies. OBJECTIVE: To determine the
      prevalence and factors influencing mis-reporting of gravidity among rural women
      in Malawi. MATERIALS AND METHODS: Data from cross sectional study conducted in
      2004 were analysed using logistic regression analysis and the logit modeling.
      RESULTS: 7118 women were in the reproductive age group, 2387(33.5%) had ever
      attended school, 4556 (64.0%) had never and results for 175 (2.5%) were missing.
      Of those who attended school, 94.9% (2297) had attained a maximum primary level,
      5.04% (122) secondary level and 0.08% (2) tertiary level. 81.6% of the women were
      aged between 12 and 36 years of age, mean was 26.1 years (SD 10.05 years). The
      remaining 18.4% were aged between 37 and 49 years of age. The mean number of
      pregnancies attained was 4.0 (SD 3.4), live births was 3.0 (SD 3.2), mean number
      of stillbirths was almost zero (SD 0.9) and the mean number of children alive was
      2.0 (SD 2.3). The prevalence of mis-reporting of gravidity was 7.9%. Factors
      influencing the risk of under-reporting gravidity were: previous experience of a
      still-birth, young age, not being married and having ever attended some level of
      education. CONCLUSIONS: We suggest that women who perceived that the community
      expected them, or they expected themselves to have fewer or no pregnancy at all,
      censured themselves in reporting low number of pregancies. Researchers using
      questionnaires should keep in mind possibility of mis-reporting of number of
      pregnancies among women as this may introduce error in research results.
      Incorporating multiple questions asking the same thing but in a different way has
      potential to identify biases as these other questions serve as consistency
      checks.

PMID- 16615847
TI  - Stevens - Johnson syndrome due to nevirapine.
AB  - A 25-year-old HIV-infected woman participating in a study of the effects of
      hormonal contraception on HIV disease progression was started on antiretroviral
      therapy-Combivir & Nevirapine (NVP) on May 27, 2004. NVP was 200mg daily
      initially for two weeks to be increased to 200mg bid thereafter. On day twelve,
      she presented with a mild skin rash on the trunk, purulent conjunctivitis,
      pharyngitis and fever. She was treated symptomatically and sent home. The
      following day she returned with a generalized erythematous eruption. She was
      admitted to JCRC (Joint Clinical and Research Centre) on June 14 and was
      diagnosed with Stevens - Johnson syndrome (SJS). Antiretroviral therapy was
      stopped. By July 05, 2004, she had improved and was discharged. After recovery
      she was restarted on Combivir and Efavirenz and is subsequently doing well on
      this regimen.

PMID- 16615848
TI  - A renal aspergilloma--an unusual presentation of aspergillosis in an HIV patient.
AB  - BACKGROUND: Aspergillosis is a fungal infection occasionally found in
      immunosuppressed patients. The recommended management of patients with renal
      aspergilloma remains unclear. METHODS: An HIV patient presented with flank pain
      and an abdominal mass. Renal aspergilloma was diagnosed. RESULTS: The patient
      with CD4 above 200 did well with nephrectomy followed by amphotericin therapy for
      14 days. CONCLUSIONS: The merits of surgery followed by antifungal chemotherapy
      or vice versa are limited. More studies are needed to ascertain the most
      effective method of treatment for Aspergillosis in HIV patients.

PMID- 16615849
TI  - Giant hydrocele--an epitome of neglect.
AB  - Hydrocele [Greek: water--sac] is abnormal fluid collection within the tunica
      vaginalis of the scrotum or a patent tunica vaginalis. It is a relatively common
      condition in surgical practice. However, a giant hydrocele, here defined for
      clinical purposes, as a hydrocele equal to or bigger than the patient's head, is
      rare as indicated by the limited number of reported cases in the literature. In
      this paper I am presenting three cases of giant hydroceles and highlighting how
      it affects the quality of patients' life by way of complications, infertility,
      sexual function and work capacity.

PMID- 16615850
TI  - Ano-perianal tuberculosis--solving a clinical dilemma.
AB  - BACKGROUND: Tuberculosis is one of the causes of granulomatous disease within the
      anorectal region. The clinical features, which include symptoms and signs of anal
      pain or discharge, multiple or recurrent fistula in ano and inguinal
      lymphadinopathy, are not characteristically distinct from other anal lesions. It
      is also difficult to distinguish it from other granulomatous diseases involving
      the same area. MATERIALS AND METHODS: A Medline database was used to perform a
      literature search for articles relating to the term 'anal', 'tuberculosis' and
      'Koch's'. CONCLUSION: Analysis of the available literature shows that Koch's
      lesion in and around the anus is not uncommon. The presentation is varied in
      nature and tuberculosis should be suspected in lesions not responding to the
      conventional approaches. The treatment is two-fold: surgical for the suppuration
      and medical for the tuberculosis.

PMID- 16615851
TI  - Widowhood in African Society and its effects on women's health.

PMID- 16615853
TI  - Sphingolipids in tumor metastases and angiogenesis.
AB  - This review article summarizes data on the involvement of sphingolipids
      (sphingosine-1-phosphate, sphingosine-1-phosphocholine, neutral
      glycosphingolipids, and gangliosides) in tumor metastases and angiogenesis.

PMID- 16615854
TI  - Two-dimensional electrophoretic proteome study of serum thermostable fraction
      from patients with various tumor conditions.
AB  - One of the problems of plasma proteomics is a presence of large major components.
      In this work, we use the thermostable fraction as a way to deplete these major
      proteins. The thermostable fraction of serum samples from patients with ovarian,
      uterus, and breast cancers and benign ovarian tumor was analyzed using two
      dimensional electrophoresis combined with MALDI-TOF(-TOF)-mass spectrometry. Of
      them, alpha-1-acid glycoprotein and clusterin are expressly down-regulated in
      breast cancer, whereas transthyretin is decreased specifically in ovarian cancer.
      Apolipoprotein A-I forms have decreased spot volumes, while haptoglobin alpha1,
      in contrast, is elevated in several tumors. These data are partly consistent with
      previous art studies on cancer proteomics, which involve mass-spectrometry-based
      serum profiling techniques. Serum thermostable fraction may be recommended as a
      good tool for medium and small protein proteome investigation, in particular, by
      2D-electrophoresis.

PMID- 16615855
TI  - L-methionine gamma-lyase from Citrobacter freundii: cloning of the gene and
      kinetic parameters of the enzyme.
AB  - It is shown for the first time for the Enterobacteriaceae family that a gene
      encoding L-methionine gamma-lyase (MGL) is present in the genome of Citrobacter
      freundii. Homogeneous enzyme has been purified from C. freundii cells and its N
      terminal sequence has been determined. The hybrid plasmid pUCmgl obtained from
      the C. freundii genomic library contains an EcoRI insert of about 3000 bp, which
      ensures the appearance of MGL activity when expressed in Escherichia coli TG1
      cells. The nucleotide sequence of the EcoRI fragment contains two open reading
      frames. The first frame (the megL gene) encodes a protein of 398 amino acid
      residues that has sequence homology with MGLs from different sources. The second
      frame encodes a protein with sequence homology with proteins belonging to the
      family of permeases. To overexpress the megL gene it was cloned into pET-15b
      vector. Recombinant enzyme has been purified and its kinetic parameters have been
      determined. It is demonstrated that a presence of a hybrid plasmid pUCmgl,
      containing the megL gene in the E. coli K12 cells, leads to a decrease in
      efficiency of EcoKI-restriction. It seems likely that decomposition of L
      methionine under the action of MGL leads to a decrease in the intracellular
      content of S-adenosylmethionine. Expression of the megL gene in the C. freundii
      genome occurs only upon induction by a significant amount of L-methionine.

PMID- 16615856
TI  - Molecular dynamics simulation of interactions in glycolytic enzymes.
AB  - Two glycolytic enzymes, phosphoglycerate mutase (PGM) and enolase from
      Saccharomyces cerevisiae, have been chosen to detect complex formation and
      possible channeling, using molecular dynamics simulation. The enzymes were
      separated by 10 angstroms distance and placed in a water-filled box of size 173 x
      173 x 173 angstroms. Three different orientations have been investigated. The two
      initial 3-phosphoglycerate substrate molecules near the active centers of the
      initial structure of PGM have been replaced with final product (2
      phosphoglycerate) molecules, and 150 mM NaCl together with three Mg2+ ions have
      been added to the system to observe post-catalytic activity under near
      physiological conditions. Analysis of interaction energies and conformation
      changes for 3 nsec simulation indicates that PGM and enolase do show binding
      affinity between their near active regions, which is necessary for channeling to
      occur. Interaction of the C-terminal residues Ala239 and Val240 of PGM (which
      partially "cap" the 2-phosphoglycerate) with enolase also favors the existence of
      channeling.

PMID- 16615857
TI  - Production of heat shock proteins, cytokines, and nitric oxide in toxic stress.
AB  - Expression of heat shock proteins Hsp27, Hsp90, and Hsp70 and production of tumor
      necrosis factors (TNF-alpha, TNF-beta), interferon-gamma (IFN-gamma), interleukin
      2, -3, -6, and nitric oxide (NO) were studied under conditions of acute and
      chronic intoxication of animals with lipopolysaccharides. Injection of endotoxin
      increased expression of heat shock proteins Hsp70 and Hsp90-alpha in mouse cells.
      Acute toxic stress also provoked a sharp increase in the production of TNF-alpha,
      TNF-beta, and NO in mouse cells. The production of other cytokines (interleukins
      and IFN-gamma) was changed insignificantly. In the model of chronic toxic stress,
      changes in the production of Hsp70, Hsp90, TNF, and NO were followed during 11
      days after the beginning of the toxin injections. The expression of Hsp70 and
      Hsp90 in acute stress was significantly higher than at the final stage of the
      chronic exposure. The changes in the TNF and NO productions, on one hand, and the
      production of heat shock proteins, on the other hand, were synchronous. The
      findings indicate that repeated injections of increasing endotoxin doses result
      in a decreased ability of the body cells to respond to stress by overproduction
      of heat shock proteins, TNF, and NO.

PMID- 16615858
TI  - H2O2 intensifies CN(-)-induced apoptosis in pea leaves.
AB  - H2O2 intensifies CN(-)-induced apoptosis in stoma guard cells and to lesser
      degree in basic epidermal cells in peels of the lower epidermis isolated from pea
      leaves. The maximum effect of H2O2 on guard cells was observed at 10(-4) M. By
      switching on non-cyclic electron transfer in chloroplasts menadione and methyl
      viologen intensified H2O2 generation in the light, but prevented the CN--induced
      apoptosis in guard cells. The light stimulation of CN- effect on guard cell
      apoptosis cannot be caused by disturbance of the ribulose-1,5-bisphosphate
      carboxylase function and associated OH* generation in chloroplasts with
      participation of free transition metals in the Fenton or Haber-Weiss type
      reactions as well as with participation of the FeS clusters of the electron
      acceptor side of Photosystem I. Menadione and methyl viologen did not suppress
      the CN(-)-induced apoptosis in epidermal cells that, unlike guard cells, contain
      mitochondria only, but not chloroplasts. Quinacrine and diphenylene iodonium,
      inhibitors of NAD(P)H oxidase of cell plasma membrane, had no effect on the
      respiration and photosynthetic O2 evolution by leaf slices, but prevented the CN(
      )-induced guard cell death. The data suggest that NAD(P)H oxidase of guard cell
      plasma membrane is a source of reactive oxygen species (ROS) needed for execution
      of CN(-)-induced programmed cell death. Chloroplasts and mitochondria were
      inefficient as ROS sources in the programmed death of guard cells. When ROS
      generation is insufficient, exogenous H2O2 exhibits a stimulating effect on
      programmed cell death. H2O2 decreased the inhibitory effects of DCMU and DNP-INT
      on the CN(-)-induced apoptosis of guard cells. Quinacrine, DCMU, and DNP-INT had
      no effect on CN(-)-induced death of epidermal cells.

PMID- 16615859
TI  - Programmed cell death in plants: effect of protein synthesis inhibitors and
      structural changes in pea guard cells.
AB  - Pea leaf epidermis incubated with cyanide displayed ultrastructural changes in
      guard cells that are typical of apoptosis. Cycloheximide, an inhibitor of
      cytoplasmic protein synthesis, and lincomycin, an inhibitor of protein synthesis
      in chloroplasts and mitochondria, produced different effects on the dynamics of
      programmed death of guard cells. According to light microscopy data,
      cycloheximide reinforced and lincomycin suppressed the CN(-)-induced destruction
      of cell nuclei. Lincomycin lowered the effect of cycloheximide in the light and
      prevented it in the dark. According to electron microscopy data, the most
      pronounced effects of cycloheximide in the presence of cyanide were autophagy and
      a lack of apoptotic condensation of nuclear chromatin, the prevention of
      chloroplast envelope rupturing and its invagination inside the stroma, and the
      appearance of particular compartments with granular inclusions in mitochondria.
      Lincomycin inhibited the CN(-)-induced ultrastructural changes in guard cell
      nuclei. The data show that programmed death of guard cells may have a combined
      scenario involving both apoptosis and autophagy and may depend on the action of
      both cytoplasm synthesized and chloroplast and mitochondrion synthesized
      proteins.

PMID- 16615860
TI  - Studies on low molecular mass phytocystatins purified from Phaseolus mungo (Urd).
AB  - In the present study two phytocystatins (thiol protease inhibitors) have been
      isolated and purified to homogeneity from Phaseolus mungo by a simple two-step
      procedure using ammonium sulfate fractionation and gel filtration on Sephacryl
      100 HR. The latter procedure yielded two peaks of the inhibitors (PMC I and PMC
      II). The pH optimum of both phytocystatins was pH 7.0; the temperature optima for
      PMC I and PMC II were 65 and 70 degrees C, respectively. The molecular masses of
      the purified phytocystatins were 19 and 17 kD, respectively, as determined by SDS
      PAGE and mass spectrometry. Antibodies raised against the purified cystatins gave
      a single precipitin line in Ouchterlony double immunodiffusion. Kinetics of
      inhibition showed that PMC I and PMC II strongly inhibit papain and ficin but not
      trypsin and chymotrypsin. Binding stoichiometry of PMC I and PMC II with both
      papain and ficin was 1 : 2. The effect of urea on PMC I and PMC II was analyzed
      by fluorescence and circular dichroism spectroscopy. The CD results suggest an
      unfolding of PMC I and PMC II accompanying a decrease in the amount of extended
      (hydrated) coil structure and an increase in sheet-like structure. FTIR results
      show that PMC I is structurally similar to PMC II. Hydrophobic interactions are
      observed over a long time scale (5-150 min). Furthermore, fluorescence
      spectroscopy results were found to be in accordance with CD results, by showing
      quenching of fluorescence intensity of PMC I and PMC II, although to different
      extents, due to perturbations of the environment of aromatic residues in the
      protein. Both cystatins showed strong inhibitory activity against Escherichia
      coli and Staphylococcus aureus.

PMID- 16615861
TI  - Proteins of the Rpf (resuscitation promoting factor) family are peptidoglycan
      hydrolases.
AB  - The secreted Micrococcus luteus protein, Rpf, is required for successful
      resuscitation of dormant "non-culturable" M. luteus cells and for growth
      stimulation in poor media. The biochemical mechanism of Rpf action remained
      unknown. Theoretical predictions of Rpf domain architecture and organization,
      together with a recent NMR analysis of the protein structure, indicate that the
      conserved Rpf domain has a lysozyme-like fold. In the present study, we found
      that both the secreted native protein and the recombinant protein lyse crude
      preparations of M. luteus cell walls. They also hydrolyze 4-methylumbelliferyl
      beta-D-N,N',N''-triacetylchitotrioside, a synthetic substrate for peptidoglycan
      muramidases, with optimum activity at pH 6. The Rpf protein also has weak
      proteolytic activity against N-CBZ-Gly-Gly-Arg-beta-naphthylamide, a substrate
      for trypsin-like enzymes. Rpf activity towards 4-methylumbelliferyl-beta-D
      N,N',N''-triacetylchitotrioside was reduced when the glutamate residue at
      position 54, invariant for all Rpf family proteins and presumably involved in
      catalysis, was altered. The same amino acid substitution resulted in impaired
      resuscitation activity of Rpf. The data indicate that Rpf is a peptidoglycan
      hydrolyzing enzyme, and strongly suggest that this specific activity is
      responsible for its growth promotion and resuscitation activity. A possible
      mechanism of Rpf-mediated resuscitation is discussed.

PMID- 16615862
TI  - Effect of brassinolide on tyrosine phosphorylation of pea leaf proteins.
AB  - Brassinosteroid-induced phosphorylation of tyrosine residues in proteins was
      studied. Proteins of crude extract of pea leaves were analyzed by one- and two
      dimensional electrophoresis followed by Western blotting with monoclonal
      antibodies PY20 to phosphotyrosine proteins. One- and two-dimensional
      electrophoresis revealed 7 and 13 tyrosine-phosphorylated proteins, respectively.
      Brassinolide increased the phosphorylation level of most of these proteins. With
      inhibitors of tyrosine protein phosphatases, such as phenylarsine oxide and
      orthovanadate, the level of tyrosine phosphorylation of these proteins increased.

PMID- 16615863
TI  - Effect of photodestruction of plastids from norflurazon-treated barley seedlings
      on expression of nuclear genes encoding chloroplast stress proteins.
AB  - The effects of photodestruction of chloroplasts in norflurazon-treated barley
      seedlings on expression of nuclear genes Elip and Hsp32 encoding light and heat
      stress proteins of barley chloroplasts and also of the Lhcb1 and RbcS genes of
      photosynthesis proteins were studied. The genes of the photosynthesis proteins
      were not transcribed upon the photodestruction of chloroplasts. However,
      transcription of the stress protein genes continued, and the transcription of the
      heat stress protein gene remained virtually at the control level, whereas the
      light stress protein gene transcription was markedly (by 30-50%) decreased, and
      this suggests chloroplast control of the Elip gene transcription. Disorders in
      the processing and a partial disturbance in the import of precursors of Hsp32 and
      Elip proteins into the plastids of the norflurazon-treated seedlings were shown.
      Data on protease analysis indicates that photodestruction of chloroplasts is
      associated with accumulation of stress protein precursors in the plastid
      envelope.

PMID- 16615865
TI  - Purification and characterization of Fe-containing superoxide dismutase from
      Methanobrevibacter arboriphilus strain AZ.
AB  - Superoxide dismutase (SOD) was purified from cells of the strict anaerobic
      methanogenic archaeon Methanobrevibacter arboriphilus strain AZ. The four-step
      purification procedure resulted in enzyme with specific activity of 3970 units/mg
      and yield of 22%. It was shown that the SOD is a Fe-containing homotetramer
      composed of subunits of 21.2 kD each. Sodium azide (13.5 mM), unlike KCN,
      inhibits the activity of the SOD. Hydrogen peroxide (0.5 mM) inactivates the
      enzyme, which is consistent with the properties of the known Fe-containing SODs
      from methanogenic Archaea.

PMID- 16615864
TI  - Effect of temperature on synthesis of polyphosphates in Yersinia
      pseudotuberculosis and Listeria monocytogenes under starvation conditions.
AB  - It was found that at low temperature (6-8 degrees C) in the absence of nitrogen
      supply and at the presence of phosphate ions in the medium, Yersinia
      pseudotuberculosis and Listeria monocytogenes are able to actively synthesize
      reserve substances as polyphosphates. Most of the bacterial polyphosphates are
      alkali-soluble, especially at the preliminary stage of cell growth (lag-phase).
      This is proved by electron microscopic studies of ultrastructure of model
      microorganisms. During a long starvation period under conditions of carbon and
      energy source deficit, L. monocytogenes and Y. pseudotuberculosis consume this
      biopolymer for biosynthetic and bioenergetic processes.

PMID- 16615866
TI  - Polymorphism of delta3,5-delta2,4-dienoyl-coenzyme A isomerase (the ECH1 gene
      product protein) in human striated muscle tissue.
AB  - Two polymorphic variants of the ECH1 gene product protein (delta3,5-delta2,4
      dienoyl-coenzyme A isomerase) have been revealed by proteomics methods in samples
      of human striated muscle tissue. These variants are identical in molecular weight
      (29.7 kD) but different in pI values (6.57 and 6.75) and in amino acid
      substitution (41 E-->A) confirmed by mass spectrometry. The same type of
      polymorphism has been detected in samples of different tissues of the same
      person, so these variants are considered (also based on other data) to be
      allelic. The rates of these alleles in two representative cohorts of Moscow and
      Minsk residents are similar.

PMID- 16615867
TI  - Modified DNA fragments specifically and irreversibly bind transcription factor NF
      kappaB in lysates of human tumor cells.
AB  - Covalent binding of a synthetic DNA fragment with eukaryotic transcription factor
      NF-kappaB has been studied in lysates of human colon carcinoma HCT-116 cells. For
      binding we used 32P-labeled 17/19 bp nucleotide DNA duplex containing an NF
      kappaB recognition site (kappaB-site) in which one of internucleotide phosphate
      groups was replaced by a chemically active trisubstituted pyrophosphate group.
      Using gel electrophoresis under denaturing conditions (Laemmli electrophoresis)
      followed by immunoblotting revealed selective irreversible binding of 32P-labeled
      DNA duplex with NF-kappaB in lysates of tumor cells in the presence of other cell
      components. Experiment on delivery of this DNA duplex containing rhodamine at 3 
      end of the modified chain in an intact cell revealed that rhodamine-labeled DNA
      penetrated through the plasma membrane of tumor cells without any additional
      delivery systems. Using fluorescent microscopy, we found that the rhodamine
      labeled DNA is initially localized in the cytoplasm. Confocal laser scanning
      microscopy revealed that subsequent treatment of the cells with TNF-alpha
      promoted partial translocation of the DNA reagent into the nucleus.

PMID- 16615868
TI  - Effect of hypermethylation of CCWGG sequences in DNA of Mesembryanthemum
      crystallinum plants on their adaptation to salt stress.
AB  - Under salt stress conditions, the level of CpNpG-methylation (N is any
      nucleoside) of the nuclear genome of the facultative halophyte Mesembryanthemum
      crystallinum in the CCWGG sequences (W = A or T) increases two-fold and is
      coupled with hypermethylation of satellite DNA on switching-over of C3
      photosynthesis to the crassulacean acid metabolism (CAM) pathway of carbon
      dioxide assimilation. The methylation pattern of the CCWGG sequences is not
      changed in both the 5'-promoter region of the gene of phosphoenolpyruvate
      carboxylase, the key enzyme of C4-photosynthesis and CAM, and in the nuclear
      ribosomal DNA. Thus, a specific CpNpG-hypermethylation of satellite DNA has been
      found under conditions of expression of a new metabolic program. The functional
      role of the CpNpG-hypermethylation of satellite DNA is probably associated with
      formation of a specialized chromatin structure simultaneously regulating
      expression of a large number of genes in the cells of M. crystallinum plants on
      their adaptation to salt stress and switching-over to CAM metabolism.

PMID- 16615869
TI  - Demography and sex work characteristics of female sex workers in India.
AB  - BACKGROUND: The majority of sex work in India is clandestine due to unfavorable
      legal environment and discrimination against female sex workers (FSWs). We report
      data on who these women are and when they get involved with sex work that could
      assist in increasing the reach of HIV prevention activities for them. METHODS:
      Detailed documentation of demography and various aspects of sex work was done
      through confidential interviews of 6648 FSWs in 13 districts in the Indian state
      of Andhra Pradesh. The demography of FSWs was compared with that of women in the
      general population. RESULTS: A total of 5010 (75.4%), 1499 (22.5%), and 139
      (2.1%) street-, home-, and brothel-based FSWs, respectively, participated.
      Comparison with women of Andhra Pradesh revealed that the proportion of those
      aged 20-34 years (75.6%), belonging to scheduled caste (35.3%) and scheduled
      tribe (10.5%), illiterate (74.7%), and of those separated/divorced (30.7%) was
      higher among FSWs (p < 0.001). The FSWs engaged in sex work for >5 years were
      more likely to be non-street-based FSWs, illiterate, living in small urban towns,
      and to have started sex work between 12-15 years of age. The mean age at starting
      sex work (21.7 years) and gap between the first vaginal intercourse and the first
      sexual intercourse in exchange for money (6.6 years) was lower for FSWs in the
      rural areas as compared with those in large urban areas (23.9 years and 8.8
      years, respectively). CONCLUSION: These data highlight that women struggling with
      illiteracy, lower social status, and less economic opportunities are especially
      vulnerable to being infected by HIV, as sex work may be one of the few options
      available to them to earn money. Recommendations for actions are made for long
      term impact on reducing the numbers of women being infected by HIV in addition to
      the current HIV prevention efforts in India.

PMID- 16615870
TI  - A new standard nomenclature for proteins related to Apx and Shroom.
AB  - Shroom is a recently-described regulator of cell shape changes in the developing
      nervous system. This protein is a member of a small family of related proteins
      that are defined by sequence similarity and in most cases by some link to the
      actin cytoskeleton. At present these proteins are named Shroom, APX, APXL, and
      KIAA1202. In light of the growing interest in this family of proteins, we propose
      here a new standard nomenclature.

PMID- 16615871
TI  - Synteny conservation between the Prunus genome and both the present and ancestral
      Arabidopsis genomes.
AB  - BACKGROUND: Due to the lack of availability of large genomic sequences for peach
      or other Prunus species, the degree of synteny conservation between the Prunus
      species and Arabidopsis has not been systematically assessed. Using the recently
      available peach EST sequences that are anchored to Prunus genetic maps and to
      peach physical map, we analyzed the extent of conserved synteny between the
      Prunus and the Arabidopsis genomes. The reconstructed pseudo-ancestral
      Arabidopsis genome, existed prior to the proposed recent polyploidy event, was
      also utilized in our analysis to further elucidate the evolutionary relationship.
      RESULTS: We analyzed the synteny conservation between the Prunus and the
      Arabidopsis genomes by comparing 475 peach ESTs that are anchored to Prunus
      genetic maps and their Arabidopsis homologs detected by sequence similarity.
      Microsyntenic regions were detected between all five Arabidopsis chromosomes and
      seven of the eight linkage groups of the Prunus reference map. An additional 1097
      peach ESTs that are anchored to 431 BAC contigs of the peach physical map and
      their Arabidopsis homologs were also analyzed. Microsyntenic regions were
      detected in 77 BAC contigs. The syntenic regions from both data sets were short
      and contained only a couple of conserved gene pairs. The synteny between peach
      and Arabidopsis was fragmentary; all the Prunus linkage groups containing
      syntenic regions matched to more than two different Arabidopsis chromosomes, and
      most BAC contigs with multiple conserved syntenic regions corresponded to
      multiple Arabidopsis chromosomes. Using the same peach EST datasets and their
      Arabidopsis homologs, we also detected conserved syntenic regions in the pseudo
      ancestral Arabidopsis genome. In many cases, the gene order and content of peach
      regions was more conserved in the ancestral genome than in the present
      Arabidopsis region. Statistical significance of each syntenic group was
      calculated using simulated Arabidopsis genome. CONCLUSION: We report here the
      result of the first extensive analysis of the conserved microsynteny using DNA
      sequences across the Prunus genome and their Arabidopsis homologs. Our study also
      illustrates that both the ancestral and present Arabidopsis genomes can provide a
      useful resource for marker saturation and candidate gene search, as well as
      elucidating evolutionary relationships between species.

PMID- 16615872
TI  - Convulsant bicuculline modifies CNS muscarinic receptor affinity.
AB  - BACKGROUND: Previous work from this laboratory has shown that the administration
      of the convulsant drug 3-mercaptopropionic acid (MP), a GAD inhibitor, modifies
      not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl
      benzilate ([3H]-QNB) to central muscarinic receptors, an effect due to an
      increase in affinity without modifications in binding site number. The
      cholinergic system has been implicated in several experimental epilepsy models
      and the ability of acetylcholine to regulate neuronal excitability in the
      neocortex is well known. To study the potential relationship between GABAergic
      and cholinergic systems with seizure activity, we analyzed the muscarinic
      receptor after inducing seizure by bicuculline (BIC), known to antagonize the
      GABA-A postsynaptic receptor subtype. RESULTS: We analyzed binding of muscarinic
      antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at
      subconvulsant (1.0 mg/kg) and convulsant (7.5 mg/kg) doses. Subconvulsant BIC
      dose failed to develop seizures but produced binding alteration in the cerebellum
      and hippocampus with roughly 40% increase and 10% decrease, respectively. After
      convulsant BIC dose, which invariably led to generalized tonic-clonic seizures,
      binding increased 36% and 15% to cerebellar and striatal membranes respectively,
      but decreased 12% to hippocampal membranes. Kd value was accordingly modified:
      with the subconvulsant dose it decreased 27% in cerebellum whereas it increased
      61% in hippocampus; with the convulsant dose, Kd value decreased 33% in
      cerebellum but increased 85% in hippocampus. No change in receptor number site
      was found, and Hill number was invariably close to unity. CONCLUSION: Results
      indicate dissimilar central nervous system area susceptibility of muscarinic
      receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose
      but also by a subconvulsant dose, indicating that changes are not attributable to
      the seizure process itself. Findings support the notion that the muscarinic
      receptors play a major role in experimental epilepsy and provide a new example of
      differential neuronal plasticity.

PMID- 16615873
TI  - Unusual histologic and clinical variants of melanoma: implications for therapy.
AB  - Unusual histologic variants of melanoma may prove problematic to the
      histopathologist. Several of these variants are sufficiently rare that their
      biological behavior remains obscure. Because identification of some of these
      melanoma subtypes has specific implications for the therapeutic approach and some
      may mimic other forms of epithelial or mesenchymal neoplasia, their recognition
      is key to patient management.

PMID- 16615874
TI  - Epidemiology and prevention of cutaneous melanoma.
AB  - Melanoma incidence has continued to increase in all white populations, and
      mortality from melanoma remains high in older men worldwide. In Australia,
      Europe, and the United States, a substantial number of thick melanomas in older
      men are of the nodular subtype, a subtype lacking asymmetry or color change.
      Educating the public and professionals about the significance of evolving
      pigmented lesions as emphasized in the revised ABCDE of pigmented lesions is
      relevant. Targeting screening efforts toward older men will be necessary to
      decrease worldwide melanoma mortality. Among prevention strategies, emphasizing
      multiple methods of sun protection in early childhood, adolescence, and adulthood
      is needed to decrease sunburn rates. Chemoprevention research in melanoma should
      become a research priority to complement ongoing prevention strategies.

PMID- 16615875
TI  - Blastic phase of chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML), also known as chronic myelocytic or chronic
      myeloid leukemia, is a clonal disorder of hematopoiesis that arises in a
      hematopoietic stem cell or early progenitor cell. This is characterized by the
      dysregulated production of mature nonlymphoid cells with normal differentiation.
      Eventually, in spite of the term chronic, there is progression to acute leukemia,
      usually of the myeloid variety, which is highly resistant to current therapies.
      Despite recent improvements in the treatment of early-stage disease, CML blast
      crisis (CMLBC) remains a therapeutic challenge. CMLBC is highly refractory to
      standard induction chemotherapy, with a response rate in myeloid blast crisis of
      less than 30%. Conventional chemotherapy has been much less successful in this
      disease compared with de novo acute leukemia, with a mean survival after
      diagnosis of blast crisis of only 2 to 4 months for nonresponders. Many regimens
      of chemotherapies have been tried in CMLBC, with minor success. Although imatinib
      was evaluated in patients with CMLBC, most CMLBC cases today arise in patients
      already on imatinib-based therapy and developing blastic phase on that therapy;
      thus there is no standard therapy for patients with CMLBC. Further studies of the
      mechanisms of transformation of chronic-phase CMLBC at a molecular level, and
      methods to target these molecular abnormalities, will determine the future
      direction of new treatment modalities. The prognosis of CML in blast crisis
      remains disappointing, despite great efforts. Currently, the most successful
      strategy for improving survival in CML is by prolonging the chronic phase and
      delaying the onset of blast crisis.

PMID- 16615876
TI  - New agents in chronic lymphocytic leukemia.
AB  - For many years, alkylating agents, especially chlorambucil, have been considered
      the drugs of choice for first-line treatment of progressive and symptomatic
      chronic lymphocytic leukemia (CLL). More recently, treatment approaches have
      included purine nucleoside analogs (PNAs), fludarabine or cladribine (2-CdA), and
      monoclonal antibodies (MoAbs). PNAs are highly active in patients with CLL,
      previously treated and untreated. Significantly higher overall response and
      complete response in patients treated initially with fludarabine or 2-CdA than in
      those treated with chlorambucil- or cyclophosphamide-based combination regimens
      have been recently confirmed in prospective, randomized trials. However, the
      median survival times do not differ among the patients treated with PNA and
      alkylating agents. The MoAbs directed against CD52 antigen (alemtuzumab) and CD20
      antigen (rituximab) also demonstrate significant activity in CLL and should be
      used in patients with disease that is refractory to PNAs. Combination therapies
      with PNAs and cyclophosphamide, and especially with rituximab, are more active
      than monotherapy with PNAs in regard to response rate and possible survival.
      Because most patients are older and there is no survival time advantage for
      alkylating agents or PNA therapies, we recommend chlorambucil as the first-line
      treatment, with PNAs for consideration as the second-line therapy. PNAs alone or
      in combination with cyclophosphamide and rituximab as first-line treatment are an
      option in younger patients, who may be candidates for consolidation therapy with
      alemtuzumab and/or stem cell transplantation. Alemtuzumab may be an effective
      treatment for patients refractory to PNAs. Several biological parameters have
      been gaining increasing importance to evaluate the prognosis of patients with CLL
      and define optimal therapeutic strategy. Moreover, novel therapies are being
      evaluated, especially in patients refractory to PNAs, including those targeting
      the antiapoptotic bcl-2 family of proteins and receptors, vaccines, and allogenic
      stem cell transplantation, especially after nonmyeloablative chemotherapy.

PMID- 16615877
TI  - Management of marginal zone lymphomas.
AB  - Marginal-zone lymphoma (MZL) includes three subtypes depending on the site of
      lymphoma involvement: extranodal marginal zone B-cell lymphoma of mucosa
      associated lymphoid tissue (MALT lymphoma); splenic MZL; and nodal MZL. Although
      there is a common cell of origin and similarities concerning a possible chronic
      antigenic stimulation by microbial pathogens and/or auto-antigens, the clinical
      presentation is very different with symptoms related to lymphoma location. MALT
      and splenic MZL present with an indolent disease with good performance status, no
      B symptoms, and no adverse prognostic factors and are associated with long
      survival. Patients with nodal MZL present with a shorter progression-free
      survival. Clinical and biological prognostic factors identified in reported
      series are heterogeneous. The optimal treatment has yet to be defined for the
      three subtypes, and current strategies are described in this review.

PMID- 16615878
TI  - Amyloidosis.
AB  - Amyloidosis is a disease in which abnormal proteins form fibrillar tissue
      deposits that can compromise key viscera and lead to early death. In order to
      treat amyloidosis, the type of abnormal protein must be identified. The most
      common type is monoclonal immunoglobulin light chain or AL amyloidosis; the other
      important type is hereditary, caused by variant forms of transthyretin and other
      proteins, whereas amyloid associated with chronic inflammation ("secondary") is
      rare in the developed world. AL can be misdiagnosed if a monoclonal gammopathy
      and a hereditary variant are present in the same patient. The aim of therapy in
      systemic AL amyloidosis is to reduce the amyloid-forming monoclonal light chain,
      measured with the serum free light chain assay, by suppressing the underlying
      plasma cell dyscrasia, while using supportive measures to sustain organ function.
      Amyloid deposits can be resorbed and organ function restored if the amyloid
      forming precursor light chain is eliminated. The most effective treatment for
      systemic AL amyloidosis is risk-adapted melphalan with peripheral blood stem cell
      transplant (SCT). The hematologic response rate is 75% at 12 months when adjuvant
      therapy with thalidomide and dexamethasone is used post-SCT. Patients can achieve
      long-term durable remissions with organ recovery. Drugs effective in multiple
      myeloma are usually helpful in AL amyloidosis if tolerated. The use of novel
      antibody-based approaches for imaging amyloid and possibly for accelerating
      removal of deposits is under active investigation.

PMID- 16615879
TI  - Smoldering multiple myeloma and monoclonal gammopathy of undetermined
      significance.
AB  - Smoldering multiple myeloma (SMM) consists of the presence of a serum M protein
      of 30 g/L or more and/or 10% or more bone marrow plasma cells (BMPCs), with no
      clinical manifestations or symptoms of myeloma. It accounts for approximately 10%
      of all myelomas, and the median time to progression to a symptomatic multiple
      myeloma ranges from 2 to 3 years. The main factors for progression are the plasma
      cell mass (M-protein size and percent of BMPCs), the spinal MRI pattern, the
      plasma cell proliferative index, and the variant of SMM ("evolving" vs
      "nonevolving"). Although treatment with thalidomide is promising (based on the
      results of two phase II trials), outside the context of a clinical trial, a watch
      and-wait approach with clinical evaluation every 4 months is recommended until
      evident symptomatic disease progression occurs. Patients with monoclonal
      gammopathy of undetermined significance (MGUS) have a serum M protein lower than
      30 g/L and a proportion of BMPCs of less than 10%, with no clinical findings or
      symptoms attributable to the monoclonal gammopathy. MGUS has a high prevalence,
      and its annual rate of malignant transformation is 1%, such that the actuarial
      probability of progression to a symptomatic monoclonal gammopathy at 25 years of
      follow-up is as high as 40%. The factors associated with a higher probability of
      malignant transformation are a relatively high plasma cell mass, immunoglobulin A
      M-protein type, and the "evolving" variant. It is recommended that patients with
      MGUS are monitored annually. Importantly, patients with asymptomatic monoclonal
      gammopathies must not be treated before the development of overt multiple
      myeloma.

PMID- 16615880
TI  - Novel treatment approaches for patients with relapsed and refractory multiple
      myeloma.
AB  - Treatment options for patients with relapsed myeloma are a rapidly moving entity.
      Although autologous transplantation has improved outcomes for younger patients,
      the use of a second autologous transplant in the relapsed setting has less
      benefit. Nonmyeloablative allogeneic transplant is being studied in several large
      cooperative group trials, but to date early auto/mini-allo does not appear to be
      superior to tandem autologous transplantation. The greatest benefit in the
      relapsed setting has been demonstrated using novel targeted agents with
      biologically based therapies. The response rates from thalidomide with and
      without dexamethasone, bortezomib, and lenalidomide with and without
      dexamethasone clearly demonstrate high levels of activity with encouraging
      durations of remission. More recent studies are combining novel agents, and small
      phase I/II trials are demonstrating higher overall response and complete
      remission rates. The next generation of novel agents targeting heat shock
      proteins, the mitogen-activated protein kinase pathway, and monoclonal antibodies
      are further expanding the list of future potential agents. The rapid clinical
      development of targeting agents will give us more options to treat patients with
      relapsed or refractory myeloma, thereby improving quality of life and overall
      survival.

PMID- 16615881
TI  - The long journey from stem cells to medical product.
AB  - There is much interest in developing stem cells and the cells derived from them
      as therapies for treating human disease and injury, but many biological,
      technological and regulatory hurdles have to be overcome before these cell
      therapies can be brought to commercial fruition.

PMID- 16615882
TI  - Turning off neurotransmitters.
AB  - The historic discovery that the catecholamine neurotransmitters of the
      sympathetic nervous system, norepinephrine and epinephrine, are inactivated
      through their reuptake by presynaptic nerve terminals provided new insights into
      neurotransmitter action and paved the way for the development of modern
      antidepressant drugs.

PMID- 16615883
TI  - NoCut: cytokinesis in check.
AB  - In this issue of Cell, Norden et al. (2006) describe a new pathway, NoCut, that
      links the completion of chromosome segregation to the onset of cytokinesis in
      budding yeast. In NoCut, Aurora kinase (Ipl1) at the spindle midzone negatively
      regulates cytokinesis through two proteins previously identified to be involved
      in cell polarity, Boi1 and Boi2.

PMID- 16615884
TI  - The meiotic chromosomal bouquet: SUN collects flowers.
AB  - In the early stages of meiosis, all the telomeres in the cell attach to the
      nuclear envelope and gather near the centrosome. This polarized chromosomal array
      is known as the bouquet, as the clustered telomeres resemble the gathered stems
      of a floral arrangement. In this issue of Cell, Chikashige et al. (2006) provide
      intriguing clues about the molecular details underlying this conserved meiotic
      event.

PMID- 16615885
TI  - Hibernation proteins: preparing for life in the freezer.
AB  - Hibernation is an extreme response to a seasonal environment, yet we know almost
      nothing about how it is timed or how vital cellular functions are sustained in
      the face of plummeting body temperature. In this issue of Cell, kondo et al.
      (2006) identify a liver-derived protein complex as an essential coordinator of
      this adaptation to the depredations of winter.

PMID- 16615886
TI  - Building bridges to the cortex.
AB  - Innervation of the neocortex by the thalamus is dependent on the precise
      coordination of spatial and temporal guidance cues. In this issue of Cell, work
      by Lopez-Bendito et al.(2006) reveals that tangentially migrating cells within
      the ventral telencephalon are essential for axonal navigation between the
      thalamus and the neocortex, a process apparently mediated by Neuregulin-1/ErbB4
      short- and long-range signaling.

PMID- 16615887
TI  - Emerging patterns in complement-mediated pathogen recognition.
AB  - Protection from acute infection requires an immediate response by the host innate
      immune system. Two recent Cell papers, including one in this issue, provide new
      insight into the role of the complement system in response to blood-borne
      pathogens.

PMID- 16615888
TI  - Nodal flow and the generation of left-right asymmetry.
AB  - The establishment of left-right asymmetry in mammals is a good example of how
      multiple cell biological processes coordinate in the formation of a basic body
      plan. The leftward movement of fluid at the ventral node, called nodal flow, is
      the central process in symmetry breaking on the left-right axis. Nodal flow is
      autonomously generated by the rotation of cilia that are tilted toward the
      posterior on cells of the ventral node. These cilia are built by transport via
      the KIF3 motor complex. How nodal flow is interpreted to create left-right
      asymmetry has been a matter of debate. Recent evidence suggests that the leftward
      movement of membrane-sheathed particles, called nodal vesicular parcels (NVPs),
      may result in the activation of the non-canonical Hedgehog signaling pathway, an
      asymmetric elevation in intracellular Ca(2+) and changes in gene expression.

PMID- 16615889
TI  - A dominant complement fixation pathway for pneumococcal polysaccharides initiated
      by SIGN-R1 interacting with C1q.
AB  - The intricate system of serum complement proteins provides resistance to
      infection. A pivotal step in the complement pathway is the assembly of a C3
      convertase, which digests the C3 complement component to form microbial binding
      C3 fragments recognized by leukocytes. The spleen and C3 provide resistance
      against blood-borne S. pneumoniae infection. To better understand the mechanisms
      involved, we studied SIGN-R1, a lectin that captures microbial polysaccharides in
      spleen. Surprisingly, conditional SIGN-R1 knockout mice developed deficits in C3
      catabolism when given S. pneumoniae or its capsular polysaccharide intravenously.
      There were marked reductions in proteolysis of serum C3, deposition of C3 on
      organisms within SIGN-R1(+) spleen macrophages, and formation of C3 ligands. We
      found that SIGN-R1 directly bound the complement C1 subcomponent, C1q, and
      assembled a C3 convertase, but without the traditional requirement for either
      antibody or factor B. The transmembrane lectin SIGN-R1 therefore contributes to
      innate resistance by an unusual C3 activation pathway.

PMID- 16615890
TI  - Meiotic proteins bqt1 and bqt2 tether telomeres to form the bouquet arrangement
      of chromosomes.
AB  - In many organisms, meiotic chromosomes are bundled at their telomeres to form a
      "bouquet" arrangement. The bouquet formation plays an important role in
      homologous chromosome pairing and therefore progression of meiosis. As meiotic
      telomere clustering occurs in response to mating pheromone signaling in fission
      yeast, we looked for factors essential for bouquet formation among genes induced
      under mating pheromone signaling. This genome-wide search identified two
      proteins, Bqt1 and Bqt2, that connect telomeres to the spindle-pole body (SPB;
      the centrosome equivalent in fungi). Neither Bqt1 nor Bqt2 alone functions as a
      connector, but together the two proteins form a bridge between Rap1 (a telomere
      protein) and Sad1 (an SPB protein). Significantly, when both Bqt1 and Bqt2 are
      ectopically expressed in mitotic cells, they also form a bridge between Rap1 and
      Sad1. Thus, a complex including Bqt1 and Bqt2 is essential for connecting
      telomeres to the SPB.

PMID- 16615891
TI  - An RNA sensor for intracellular Mg(2+).
AB  - Most RNA molecules require Mg(2+) for their structure and enzymatic properties.
      Here we report the first example of an RNA serving as sensor for cytoplasmic
      Mg(2+). We establish that expression of the Mg(2+) transporter MgtA of Salmonella
      enterica serovar Typhimurium is controlled by its 5' untranslated region (5'UTR).
      We show that the 5'UTR of the mgtA gene can adopt different stem-loop structures
      depending on the Mg(2+) levels, which determine whether transcription reads
      through into the mgtA coding region or stops within the 5'UTR. We could
      recapitulate the Mg(2+)-regulated transcription using a defined in vitro
      transcription system with RNA polymerase as the only protein component. The
      initiation of mgtA transcription responds to extracytoplasmic Mg(2+) and its
      elongation into the coding region to cytoplasmic Mg(2+), providing a singular
      example in which the same ligand is sensed in different cellular compartments to
      regulate disparate steps in gene transcription.

PMID- 16615892
TI  - The NoCut pathway links completion of cytokinesis to spindle midzone function to
      prevent chromosome breakage.
AB  - During anaphase, spindle elongation pulls sister chromatids apart until each pair
      is fully separated. In turn, cytokinesis cleaves the cell between the separated
      chromosomes. What ensures that cytokinesis proceeds only after that all
      chromosome arms are pulled out of the cleavage plane was unknown. Here, we show
      that a signaling pathway, which we call NoCut, delays the completion of
      cytokinesis in cells with spindle-midzone defects. NoCut depends on the Aurora
      kinase Ipl1 and the anillin-related proteins Boi1 and Boi2, which localize to the
      site of cleavage in an Ipl1-dependent manner and act as abscission inhibitors.
      Inactivation of NoCut leads to premature abscission and chromosome breakage by
      the cytokinetic machinery and is lethal in cells with spindle-elongation defects.
      We propose that NoCut monitors clearance of chromatin from the midzone to ensure
      that cytokinesis completes only after all chromosomes have migrated to the poles.

PMID- 16615893
TI  - ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking
      to ESCRT-I and membranes.
AB  - ESCRT complexes form the main machinery driving protein sorting from endosomes to
      lysosomes. Currently, the picture regarding assembly of ESCRTs on endosomes is
      incomplete. The structure of the conserved heterotrimeric ESCRT-I core presented
      here shows a fan-like arrangement of three helical hairpins, each corresponding
      to a different subunit. Vps23/Tsg101 is the central hairpin sandwiched between
      the other subunits, explaining the critical role of its "steadiness box" in the
      stability of ESCRT-I. We show that yeast ESCRT-I links directly to ESCRT-II,
      through a tight interaction of Vps28 (ESCRT-I) with the yeast-specific zinc
      finger insertion within the GLUE domain of Vps36 (ESCRT-II). The crystal
      structure of the GLUE domain missing this insertion reveals it is a split PH
      domain, with a noncanonical lipid binding pocket that binds PtdIns3P. The
      simultaneous and reinforcing interactions of ESCRT-II GLUE domain with membranes,
      ESCRT-I, and ubiquitin are critical for ubiquitinated cargo progression from
      early to late endosomes.

PMID- 16615894
TI  - Structural and functional organization of the ESCRT-I trafficking complex.
AB  - The endosomal sorting complex required for transport (ESCRT) complexes are
      central to receptor downregulation, lysosome biogenesis, and budding of HIV. The
      yeast ESCRT-I complex contains the Vps23, Vps28, and Vps37 proteins, and its
      assembly is directed by the C-terminal steadiness box of Vps23, the N-terminal
      half of Vps28, and the C-terminal half of Vps37. The crystal structures of a
      Vps23:Vps28 core subcomplex and the Vps23:Vps28:Vps37 core were solved at 2.1 and
      2.8 A resolution. Each subunit contains a structurally similar pair of helices
      that form the core. The N-terminal domain of Vps28 has a hydrophobic binding site
      on its surface that is conformationally dynamic. The C-terminal domain of Vps28
      binds the ESCRT-II complex. The structure shows how ESCRT-I is assembled by a
      compact core from which the Vps23 UEV domain, the Vps28 C domain, and other
      domains project to bind their partners.

PMID- 16615896
TI  - Coding of odors by a receptor repertoire.
AB  - We provide a systematic analysis of how odor quality, quantity, and duration are
      encoded by the odorant receptor repertoire of the Drosophila antenna. We test the
      receptors with a panel of over 100 odors and find that strong responses are
      sparse, with response density dependent on chemical class. Individual receptors
      range along a continuum from narrowly tuned to broadly tuned. Broadly tuned
      receptors are most sensitive to structurally similar odorants. Strikingly,
      inhibitory responses are widespread among receptors. The temporal dynamics of the
      receptor repertoire provide a rich representation of odor quality, quantity, and
      duration. Receptors with similar odor sensitivity often map to widely dispersed
      glomeruli in the antennal lobe. We construct a multidimensional "odor space"
      based on the responses of each individual receptor and find that the positions of
      odors depend on their chemical class, concentration, and molecular complexity.
      The space provides a basis for predicting behavioral responses to odors.

PMID- 16615895
TI  - Tangential neuronal migration controls axon guidance: a role for neuregulin-1 in
      thalamocortical axon navigation.
AB  - Neuronal migration and axon guidance constitute fundamental processes in brain
      development that are generally studied independently. Although both share common
      mechanisms of cell biology and biochemistry, little is known about their
      coordinated integration in the formation of neural circuits. Here we show that
      the development of the thalamocortical projection, one of the most prominent
      tracts in the mammalian brain, depends on the early tangential migration of a
      population of neurons derived from the ventral telencephalon. This tangential
      migration contributes to the establishment of a permissive corridor that is
      essential for thalamocortical axon pathfinding. Our results also demonstrate that
      in this process two different products of the Neuregulin-1 gene, CRD-NRG1 and Ig
      NRG1, mediate the guidance of thalamocortical axons. These results show that
      neuronal tangential migration constitutes a novel mechanism to control the timely
      arrangement of guidance cues required for axonal tract formation in the mammalian
      brain.

PMID- 16615897
TI  - Circannual control of hibernation by HP complex in the brain.
AB  - Seasonal hibernation in mammals is under a unique adaptation system that protects
      organisms from various harmful events, such as lowering of body temperature (Tb),
      during hibernation. However, the precise factors controlling hibernation remain
      unknown. We have previously demonstrated a decrease in hibernation-specific
      protein (HP) complex in the blood of chipmunks during hibernation. Here, HP is
      identified as a candidate hormone for hibernation. In chipmunks kept in constant
      cold and darkness, HP is regulated by an individual free-running circannual
      rhythm that correlates with hibernation. The level of HP complex in the brain
      increases coincident with the onset of hibernation. Such HP regulation proceeds
      independently of Tb changes in constant warmth, and Tb decreases only when brain
      HP is increased in the cold. Blocking brain HP activity using an antibody
      decreases the duration of hibernation. We suggest that HP, a target of
      endogenously generated circannual rhythm, carries hormonal signals essential for
      hibernation to the brain.

PMID- 16615898
TI  - Global survey of organ and organelle protein expression in mouse: combined
      proteomic and transcriptomic profiling.
AB  - Organs and organelles represent core biological systems in mammals, but the
      diversity in protein composition remains unclear. Here, we combine subcellular
      fractionation with exhaustive tandem mass spectrometry-based shotgun sequencing
      to examine the protein content of four major organellar compartments (cytosol,
      membranes [microsomes], mitochondria, and nuclei) in six organs (brain, heart,
      kidney, liver, lung, and placenta) of the laboratory mouse, Mus musculus. Using
      rigorous statistical filtering and machine-learning methods, the subcellular
      localization of 3274 of the 4768 proteins identified was determined with high
      confidence, including 1503 previously uncharacterized factors, while tissue
      selectivity was evaluated by comparison to previously reported mRNA expression
      patterns. This molecular compendium, fully accessible via a searchable web
      browser interface, serves as a reliable reference of the expressed tissue and
      organelle proteomes of a leading model mammal.

PMID- 16615899
TI  - A mammalian organelle map by protein correlation profiling.
AB  - Protein localization to membrane-enclosed organelles is a central feature of
      cellular organization. Using protein correlation profiling, we have mapped 1,404
      proteins to ten subcellular locations in mouse liver, and these correspond with
      enzymatic assays, marker protein profiles, and confocal microscopy. These
      localizations allowed assessment of the specificity in published organellar
      proteomic inventories and demonstrate multiple locations for 39% of all
      organellar proteins. Integration of proteomic and genomic data enabled us to
      identify networks of coexpressed genes, cis-regulatory motifs, and putative
      transcriptional regulators involved in organelle biogenesis. Our analysis ties
      biochemistry, cell biology, and genomics into a common framework for organelle
      analysis.

PMID- 16615900
TI  - I Siah substrate!
AB  - Proteins are targeted to the E3 RING ubiquitin ligase Siah through a PxAxVxP
      degron motif. In this issue of Structure, House et al. (2006) present the
      structural basis by which Siah recognizes its degron with high affinity and
      specificity.

PMID- 16615901
TI  - A monotopic membrane protein goes solo.
AB  - Carnitine palmitoyltransferases (CPTs) are part of the enzymatic system that
      imports fatty acids into mitochondria. The crystal structure of rat CPT-2 by
      Rufer et al. (2006) (this issue of Structure) reveals a Y-shaped tunnel for
      binding the CoA and acyl-carnitine substrates and a hydrophobic insert mediating
      membrane association.

PMID- 16615902
TI  - Shedding UV light on the phase problem.
AB  - In this issue of Structure, Nanao and Ravelli (2006) describe the use of UV
      induced radiation damage (UV-RIP) to solve the phase problem for proteins,
      employing single-wavelength X-ray radiation, without the need for derivatization.
      This should also permit data collection for many proteins on home sources,
      without travel to a synchrotron.

PMID- 16615903
TI  - ESCRT complexes assembled and GLUEd.
AB  - The ESCRT-I, -II, and -III complexes act sequentially to sort monoubiquitinated
      transmembrane proteins into multivesicular bodies for targeted degradation in the
      lysosome. Two papers published in a recent issue of Cell provide insights into
      the structural organization and functional interactions of the ESCRT-I complex
      and ESCRT-II GLUE domain.

PMID- 16615904
TI  - Bridging conformational dynamics and function using single-molecule spectroscopy.
AB  - In a typical structure-function relation study, the primary structure of proteins
      or nucleic acids is changed by mutagenesis and its functional effect is measured
      via biochemical means. Single-molecule spectroscopy has begun to give a whole new
      meaning to the "structure-function relation" by measuring the real-time
      conformational changes of individual biological macromolecules while they are
      functioning. This review discusses a few recent examples: untangling internal
      chemistry and conformational dynamics of a ribozyme, branch migration landscape
      of a Holliday junction at a single-step resolution, tRNA selection and dynamics
      in a ribosome, repetitive shuttling and snapback of a helicase, and discrete
      rotation of an ATP synthase.

PMID- 16615905
TI  - HIV-1 coreceptor selectivity: structural analogy between HIV-1 V3 regions and
      chemokine beta-hairpins is not the explanation.

PMID- 16615907
TI  - Protease accessibility laddering: a proteomic tool for probing protein structure.
AB  - Limited proteolysis is widely used in biochemical and crystallographic studies to
      determine domain organization, folding properties, and ligand binding activities
      of proteins. The method has limitations, however, due to the difficulties in
      obtaining sufficient amounts of correctly folded proteins and in interpreting the
      results of the proteolysis. A new limited proteolysis method, named protease
      accessibility laddering (PAL), avoids these complications. In PAL, tagged
      proteins are purified on magnetic beads in their natively folded state. While
      attached to the beads, proteins are probed with proteases. Proteolytic fragments
      are eluted and detected by immunoblotting with antibodies against the tag (e.g.,
      Protein A, GFP, and 6xHis). PAL readily detects domain boundaries and flexible
      loops within proteins. A combination of PAL and comparative protein structure
      modeling allows characterization of previously unknown structures (e.g., Sec31, a
      component of the COPII coated vesicle). PAL's high throughput should greatly
      facilitate structural genomic and proteomic studies.

PMID- 16615908
TI  - The endosome-associated protein Hrs is hexameric and controls cargo sorting as a
      "master molecule".
AB  - The structure of the endosomal-associated protein, Hrs, has been determined with
      cryo-electron microscopy. Hrs interacts with a number of proteins, including SNAP
      25 and STAM1, forming a complex that binds ubiquitin moieties. Analytical
      ultracentrifugation studies revealed that Hrs exists as a hexamer. The symmetry
      and the structure of the hexameric form of Hrs were determined with the single
      particle reconstruction method. Hrs comprises three antiparallel dimers with a
      central core and distinct caps on either end. Crystal structures of VHS and FYVE
      domains fit into the Hrs end caps in the EM density map. Thus, the location of
      domains that interact with the endosomal membrane, the VHS, FYVE, and C-terminal
      domains, facilitates the anchorage of Hrs to the membrane, initiating the
      functional processes of Hrs on the endosome. Based on our model, the Hrs hexamer
      interacts with the membrane and acts as a "master molecule" that presents
      multiple sites for protein binding.

PMID- 16615909
TI  - Fluorescence-detection size-exclusion chromatography for precrystallization
      screening of integral membrane proteins.
AB  - Formation of well-ordered crystals of membrane proteins is a bottleneck for
      structure determination by X-ray crystallography. Nevertheless, one can increase
      the probability of successful crystallization by precrystallization screening, a
      process by which one analyzes the monodispersity and stability of the protein
      detergent complex. Traditionally, this has required microgram to milligram
      quantities of purified protein and a concomitant investment of time and
      resources. Here, we describe a rapid and efficient precrystallization screening
      strategy in which the target protein is covalently fused to green fluorescent
      protein (GFP) and the resulting unpurified protein is analyzed by fluorescence
      detection size-exclusion chromatography (FSEC). This strategy requires only
      nanogram quantities of unpurified protein and allows one to evaluate localization
      and expression level, the degree of monodispersity, and the approximate molecular
      mass. We show the application of this precrystallization screening to four
      membrane proteins derived from prokaryotic or eukaryotic organisms.

PMID- 16615910
TI  - Flexibility and conformational entropy in protein-protein binding.
AB  - To better understand the interplay between protein-protein binding and protein
      dynamics, we analyzed molecular dynamics simulations of 17 protein-protein
      complexes and their unbound components. Complex formation does not restrict the
      conformational freedom of the partner proteins as a whole, but, rather, it leads
      to a redistribution of dynamics. We calculate the change in conformational
      entropy for seven complexes with quasiharmonic analysis. We see significant loss,
      but also increased or unchanged conformational entropy. Where comparison is
      possible, the results are consistent with experimental data. However, stringent
      error estimates based on multiple independent simulations reveal large
      uncertainties that are usually overlooked. We observe substantial gains of pseudo
      entropy in individual partner proteins, and we observe that all complexes retain
      residual stabilizing intermolecular motions. Consequently, protein flexibility
      has an important influence on the thermodynamics of binding and may disfavor as
      well as favor association. These results support a recently proposed unified
      model for flexible protein-protein association.

PMID- 16615911
TI  - Elucidation of the substrate binding site of Siah ubiquitin ligase.
AB  - The Siah family of RING proteins function as ubiquitin ligase components,
      contributing to the degradation of multiple targets involved in cell growth,
      differentiation, angiogenesis, oncogenesis, and inflammation. Previously, a
      binding motif (degron) was recognized in many of the Siah degradation targets,
      suggesting that Siah itself may facilitate substrate recognition. We report the
      crystal structure of the Siah in complex with a peptide containing the degron
      motif. Binding is within a groove formed in part by the zinc fingers and the
      first two beta strands of the TRAF-C domain of Siah. We show that residues in the
      degron, previously described to facilitate binding to Siah, interact with the
      protein. Mutagenesis of Siah at sites of interaction also abrogates both in vitro
      peptide binding and destabilization of a known Siah target.

PMID- 16615912
TI  - Crystal structure of the HP1-EMSY complex reveals an unusual mode of HP1 binding.
AB  - Heterochromatin protein-1 (HP1) plays an essential role in both the assembly of
      higher-order chromatin structure and epigenetic inheritance. The C-terminal
      chromo shadow domain (CSD) of HP1 is responsible for homodimerization and
      interaction with a number of chromatin-associated nonhistone proteins, including
      EMSY, which is a BRCA2-interacting protein that has been implicated in the
      development of breast and ovarian cancer. We have determined the crystal
      structure of the HP1beta CSD in complex with the N-terminal domain of EMSY at 1.8
      A resolution. Surprisingly, the structure reveals that EMSY is bound by two HP1
      CSD homodimers, and the binding sequences differ from the consensus HP1 binding
      motif PXVXL. This structural information expands our understanding of HP1 binding
      specificity and provides insights into interactions between HP1 homodimers that
      are likely to be important for heterochromatin formation.

PMID- 16615913
TI  - The crystal structure of carnitine palmitoyltransferase 2 and implications for
      diabetes treatment.
AB  - Carnitine palmitoyltransferases 1 and 2 (CPTs) facilitate the import of long
      chain fatty acids into mitochondria. Modulation of the catalytic activity of the
      CPT system is currently under investigation for the development of novel drugs
      against diabetes mellitus. We report here the 1.6 A resolution structure of the
      full-length mitochondrial membrane protein CPT-2. The structure of CPT-2 in
      complex with the generic CPT inhibitor ST1326 ([R]-N-[tetradecylcarbamoyl]
      aminocarnitine), a substrate analog mimicking palmitoylcarnitine and currently in
      clinical trials for diabetes mellitus treatment, was solved at 2.5 A resolution.
      These structures of CPT-2 provide insight into the function of residues involved
      in substrate binding and determination of substrate specificity, thereby
      facilitating the rational design of antidiabetic drugs. We identify a sequence
      insertion found in CPT-2 that mediates membrane localization. Mapping of
      mutations described for CPT-2 deficiency, a hereditary disorder of lipid
      metabolism, implies effects on substrate recognition and structural integrity of
      CPT-2.

PMID- 16615914
TI  - Structure of a Leu3-DNA complex: recognition of everted CGG half-sites by a
      Zn2Cys6 binuclear cluster protein.
AB  - Gal4 is the prototypical Zn2Cys6 binuclear cluster transcriptional regulator that
      binds as a homodimer to DNA containing inverted CGG half-sites. Leu3, a member of
      this protein family, binds to everted (opposite polarity to inverted) CGG half
      sites, and an H50C mutation within the Leu3 Zn2Cys6 binuclear motif abolishes its
      transcriptional repression function without impairing DNA binding. We report the
      X-ray crystal structures of DNA complexes with Leu3 and Leu3(H50C) and solution
      DNA binding studies of selected Leu3 mutant proteins. These studies reveal the
      molecular details of everted CGG half-site recognition, and suggest a role for
      the H50C mutation in transcriptional repression. Comparison with the Gal4-DNA
      complex shows an unexpected conservation in the DNA recognition mode of inverted
      and everted CGG half-sites, and points to a critical function of a linker region
      between the Zn2Cys6 binuclear cluster and dimerization regions in DNA binding
      specificity. Broader implications of these findings are discussed.

PMID- 16615915
TI  - An incoming nucleotide imposes an anti to syn conformational change on the
      templating purine in the human DNA polymerase-iota active site.
AB  - Substrate-induced conformational change of the protein is the linchpin of
      enzymatic reactions. Replicative DNA polymerases, for example, convert from an
      open to a closed conformation in response to dNTP binding. Human DNA polymerase
      iota (hPoliota), a member of the Y family of DNA polymerases, differs strikingly
      from other polymerases in its much higher proficiency and fidelity for nucleotide
      incorporation opposite template purines than opposite template pyrimidines. We
      present here a crystallographic analysis of hPoliota binary complexes, which
      together with the ternary complexes show that, contrary to replicative DNA
      polymerases, the DNA, and not the polymerase, undergoes the primary substrate
      induced conformational change. The incoming dNTP "pushes" templates A and G from
      the anti to the syn conformation dictated by a rigid hPoliota active site.
      Together, the structures posit a mechanism for template selection wherein dNTP
      binding induces a conformational switch in template purines for productive
      Hoogsteen base pairing.

PMID- 16615916
TI  - Magnesium-induced assembly of a complete DNA polymerase catalytic complex.
AB  - The molecular details of the nucleotidyl transferase reaction have remained
      speculative, as strategies to trap catalytic intermediates for structure
      determination utilize substrates lacking the primer terminus 3'-OH and catalytic
      Mg2+, resulting in an incomplete and distorted active site geometry. Since the
      geometric arrangement of these essential atoms will impact chemistry, structural
      insight into fidelity strategies has been hampered. Here, we present a crystal
      structure of a precatalytic complex of a DNA polymerase with bound substrates
      that include the primer 3'-OH and catalytic Mg2+. This catalytic intermediate was
      trapped with a nonhydrolyzable deoxynucleotide analog. Comparison with two new
      structures of DNA polymerase beta lacking the 3'-OH or catalytic Mg2+ is
      described. These structures provide direct evidence that both atoms are required
      to achieve a proper geometry necessary for an in-line nucleophilic attack of O3'
      on the alphaP of the incoming nucleotide.

PMID- 16615917
TI  - Biochemical characterization and crystal structure of Synechocystis arogenate
      dehydrogenase provide insights into catalytic reaction.
AB  - The extreme diversity in substrate specificity, and in the regulation mechanism
      of arogenate/prephenate dehydrogenase enzymes in nature, makes a comparative
      structural study of these enzymes of great interest. We report here on the
      biochemical and structural characterization of arogenate dehydrogenase from
      Synechocystis sp. (TyrAsy). This work paves the way for the understanding of the
      structural determinants leading to diversity in substrate specificity, and of the
      regulation mechanisms of arogenate/prephenate dehydrogenases. The overall
      structure of TyrAsy in complex with NADP was refined to 1.6 A. The asymmetric
      unit contains two TyrAsy homodimers, with each monomer consisting of a nucleotide
      binding N-terminal domain and a particularly unique alpha-helical C-terminal
      dimerization domain. The substrate arogenate was modeled into the active site.
      The model of the ternary complex enzyme-NADP-arogenate nicely reveals at the
      atomic level the concerted mechanism of the arogenate/prephenate dehydrogenase
      reaction.

PMID- 16615918
TI  - Structural basis for NHERF recognition by ERM proteins.
AB  - The Na+/H+ exchanger regulatory factor (NHERF) is a key adaptor protein involved
      in the anchoring of ion channels and receptors to the actin cytoskeleton through
      binding to ERM (ezrin/radixin/moesin) proteins. NHERF binds the FERM domain of
      ERM proteins, although NHERF has no signature Motif-1 sequence for FERM binding
      found in adhesion molecules. The crystal structures of the radixin FERM domain
      complexed with the NHERF-1 and NHERF-2 C-terminal peptides revealed a peptide
      binding site of the FERM domain specific for the 13 residue motif
      MDWxxxxx(L/I)Fxx(L/F) (Motif-2), which is distinct from Motif-1. This Motif-2
      forms an amphipathic alpha helix for hydrophobic docking to subdomain C of the
      FERM domain. This docking causes induced-fit conformational changes in subdomain
      C and affects binding to adhesion molecule peptides, while the two binding sites
      are not overlapped. Our studies provide structural paradigms for versatile ERM
      linkages between membrane proteins and the cytoskeleton.

PMID- 16615919
TI  - Phasing macromolecular structures with UV-induced structural changes.
AB  - Experimental phasing of macromolecular crystal structures relies on the accurate
      measurement of two or more sets of reflections from isomorphous crystals, where
      the scattering power of a few atoms is different for each set. Recently, it was
      demonstrated that X-ray-induced intensity differences can also contain phasing
      information, exploiting specific structural changes characteristic of X-ray
      damage. This method (radiation damage-induced phasing; RIP) has the advantage
      that it can be performed on a single crystal of the native macromolecule.
      However, a drawback is that X-rays introduce many small changes to both solvent
      and macromolecule. In this study, ultraviolet (UV) radiation has been used to
      induce specific changes in the macromolecule alone, leading to a larger contrast
      between radiation-susceptible and nonsusceptible sites. Unlike X-ray RIP, UV RIP
      does not require the use of a synchrotron. The method has been demonstrated for a
      series of macromolecules.

PMID- 16615920
TI  - Microarray technology in obstetrics and gynecology: a guide for clinicians.
AB  - Microarrays can be constructed with dozens to millions of probes on their surface
      to allow high-throughput analyses of many biologic processes to be performed
      simultaneously on the same sample. Microarrays are now widely used for gene
      expression analysis, deoxyribonucleic acid resequencing, single-nucleotide
      polymorphism genotyping, and comparative genomic hybridization. Microarray
      technology is accelerating research in many fields and now microarrays are moving
      into clinical application. This review discusses the emerging role of microarrays
      in molecular diagnostics, pathogen detection, oncology, and pharmacogenomics.

PMID- 16615921
TI  - Fetal sex and intrauterine growth restriction.

PMID- 16615922
TI  - Nasal bone assessment in prenatal screening for trisomy 21.
AB  - A small nose is a common facial feature of individuals with trisomy 21. Evidence
      based on radiologic, histomorphologic, and sonographic studies shows that nasal
      bone abnormalities are significantly more common in trisomy 21 fetuses than in
      euploid fetuses. These abnormalities, which include both nasal bone absence and
      short nasal bone length, can be detected by prenatal ultrasound. In this article
      we review the evidence and discuss the potential value of assessment of the fetal
      nasal bone in screening for trisomy 21.

PMID- 16615924
TI  - First-trimester Doppler investigation of the uterine circulation.
AB  - There is now strong evidence that fetal events can significantly impact postnatal
      health and disease development. Doppler velocimetry can identify some early
      pathologic changes in pregnancy. Many investigators have tried to delineate the
      normal and pathologic models of the uterine circulation in the first trimester,
      but much has yet to be defined. A discrete amount of confusion derives from the
      incomplete knowledge of the initial placental development, and particularly the
      development of the intervillous circulation. This article comprehensively reviews
      the literature on first-trimester Doppler in both normal and complicated
      pregnancies, and briefly discusses potential future areas of application.

PMID- 16615925
TI  - Localization and expression of prostaglandin E2 receptors in human placenta and
      corresponding fetal membranes with labor.
AB  - OBJECTIVE: The effects of prostaglandin E2 (PGE2) are mediated through G-protein
      coupled receptors, acting via different second messengers. The aim of this study
      was to characterize the temporal and tissue specific localization and expression
      of the PGE2 receptor subtypes (EP1-4) in uteroplacental tissues during human
      pregnancy. STUDY DESIGN: Placenta and fetal membranes were collected after
      delivery at preterm or term, each with or without labor. The localization and
      expression of the PGE2 receptor subtypes were determined by immunohistochemistry
      and Western blot. RESULTS: All 4 receptors were expressed in the placenta and
      fetal membranes; only EP3 was present in the syncytiotrophoblast layer. EP1 to
      EP4 were consistently expressed across gestation in the fetal membranes; however,
      a different cellular localization with labor was observed in the amnion for EP1,
      EP2, and EP4. CONCLUSION: The presence of these receptors in the placenta and
      fetal membranes may indicate autocrine roles for PGE2 in the signaling pathways
      associated with placental function and parturition.

PMID- 16615926
TI  - Does magnesium sulfate reduce the short- and long-term requirements for pain
      relief after caesarean delivery? A double-blind placebo-controlled trial.
AB  - OBJECTIVE: The purpose of this study was to determine whether magnesium sulfate
      decreases postoperative pain and analgesic consumption. STUDY DESIGN: Women who
      underwent elective cesarean delivery were randomized into groups according to
      high-dose magnesium sulfate (50 mg/kg load and 2 g/h), low-dose magnesium sulfate
      (25 mg/kg load and 1 g/h), or placebo. Before the delivery, the dose of patient
      controlled opioid that was used and the visual analogs of pain during the first
      48 hours after delivery and at 6 weeks were assessed. RESULTS: Forty-two women
      were assigned randomly to the high-dose arm; 38 women were assigned to the low
      dose magnesium arms, and 40 women were assigned to the control arm. The
      cumulative opioid use (P = .636); pain scores at 6, 12, 24, and 48 hours at rest
      (P = .786) and with movement (P = .179); the use of analgesics after hospital
      discharge (P = .711); and wound pain with movement (P = .429) or pressure (P =
      .144) after 6 weeks were similar. CONCLUSION: Magnesium sulfate does not reduce
      the severity of short-term or long-term (6 weeks) pain after cesarean delivery.

PMID- 16615927
TI  - Working with certified nurse-midwives does not increase obstetrical liability.

PMID- 16615929
TI  - Transactions from the Association of Professors of Obstetrics and
      Gynecology/Council on Resident Education in Obstetrics and Gynecology Annual
      Meeting. Orlando, Florida, USA. March 3, 2006.

PMID- 16615930
TI  - Detection of mutations using microarrays of poly(C)10-poly(T)10 modified DNA
      probes immobilized on agarose films.
AB  - Allele-specific hybridization to a DNA microarray can be a useful method for
      genotyping patient DNA. In this article, we demonstrate that 13- to 17-base
      oligonucleotides tagged with a poly(T)10-poly(C)10 tail (TC tag), but otherwise
      unmodified, can be crosslinked by UV light irradiation to an agarose film grafted
      onto unmodified glass. Microarrays of TC-tagged probes immobilized on the agarose
      film can be used to diagnose mutations in the human beta-globin gene, which
      encodes the beta-chains in hemoglobin. Although the probes differed widely
      regarding melting point temperature ( approximately 20 degrees C), a single
      stringency wash still gave sufficiently high discrimination signals between
      perfect match and mismatch probes to allow robust mutation detection. In all, 270
      genotypings were performed on patient materials, and no genotype was incorrectly
      classified. Quality control experiments conducted using a target DNA specific for
      the TC tag of the immobilized probes showed that the spotting and hybridization
      procedure had a variance of 20%, indicating that signal differences as low as
      twofold could be detected between perfect match and mismatch. Together, our
      results show that the use of microarrays of TC-tagged probes that have been
      immobilized on agarose films grafted onto glass is a robust and inexpensive
      genotyping method.

PMID- 16615931
TI  - [Long term outcome following 26 surgical ampullectomies].
AB  - BACKGROUND: Pancreaticoduodenectomy (PD) is the standard surgical treatment for
      malignant ampullomas but is still associated with a mortality and morbidity still
      ranging from 0 to 10% and from 15 to 40%, respectively. Ampullectomy is an
      alternative to PD for benign ampulloma or, in high-risk patients, for invasive
      carcinoma. The aim of this study was to report early and long term results of
      surgical ampullectomy for presumed benign ampullomas. PATIENTS AND METHODS: From
      1981 to 2004, 26 patients from two institutions underwent surgical ampullectomy.
      Of the 26 patients, 8 had familial adenomatous polyposis (FAP). Surgical
      ampullectomy was indicated on a multisciplinary basis. RESULTS: Final
      pathological examination revealed 15 adenomas, 4 in situ adenocarcinomas, 2
      endocrine tumors, and 5 other benign lesions. There was no postoperative
      mortality. Specific morbidity was 8% (N=2). Mean follow-up was 86+/-70 months
      (range: 3-204). Actuarial overall 5-year survival was 92%. There were 4 local
      recurrences (none in patients with FAP). Four patients died during follow-up
      (including 3 from initial disease). CONCLUSION: Ampullectomy is a good
      alternative to PD in case of benign or non-invasive malignant ampullary lesion,
      including in selected cases of FAP.

PMID- 16615932
TI  - HIV-1 Tat interaction with cyclin T1 represses mannose receptor and the bone
      morphogenetic protein receptor-2 transcription.
AB  - Macrophage transcription is significantly altered by HIV-1 infection. HIV Tat, an
      immediate-early product of the viral lifecycle, interacts with host transcription
      factors to alter host gene expression. We have previously shown that Tat
      represses transcription from the mannose receptor (MR) and the bone morphogenetic
      protein receptor-2 (BMPR2) promoters. The current study shows that
      transcriptional repression of these receptors involves Tat interaction with
      cyclin T1. Assays using U937 human monocytic cells transiently expressing MR or
      BMPR2 promoter-luciferase constructs demonstrated equal repression by one- and
      two-exon Tat gene products. A mutant Tat expression vector encoding Tat protein
      lacking the cyclin T1 binding domain failed to inhibit MR and BMPR2 promoter
      activities. Over-expression of cyclin T1 in the presence of wild-type Tat
      resulted in recovered activity from both promoters. Finally, two inhibitors of
      cyclin-dependent kinase 9 (a dominant negative CDK9 and flavopiridol) repressed
      activity from the MR and BMPR2 promoters.

PMID- 16615933
TI  - Chaperone-like activity of alpha-crystallin toward aldose reductase oxidatively
      stressed by copper ion.
AB  - The protective action of alpha-crystallin against copper-induced protein stress
      is studied using bovine lens aldose reductase (ALR2) as protein model. The
      oxidative inactivation of ALR2 induced by CuCl2 at the stoichiometric Cu2+/ALR2
      ratio of 2/1 [I. Cecconi, M. Moroni, P.G. Vilardo, M. Dal Monte, P. Borella, G.
      Rastelli, L. Costantino, D. Garland, D. Carper, J.M. Petrash, A. Del Corso, U.
      Mura, Biochemistry 37 (1998) 14167-14174] is accompanied by protein aggregation
      phenomena when the metal ion concentration is increased (Cu2+/ALR2>3). Protein
      oxidation precedes protein precipitation. Both inactivation and precipitation of
      ALR2 are prevented by alpha-crystallin in a concentration-dependent manner. The
      rationale for the stabilization of ALR2 exerted by alpha-crystallin at low metal
      concentration is given on the basis of the ability of alpha-crystallin to chelate
      copper. However, the overall protective action exerted by alpha-crystallin at
      higher copper concentration may be explained invoking the contribution of the
      special features of alpha-crystallin to easily interact with target proteins
      undergoing structural rearrangement.

PMID- 16615934
TI  - Domain stability in the AAA+ ATPase ClpB from Escherichia coli.
AB  - ClpB is a heat-shock protein that reactivates aggregated proteins in cooperation
      with the DnaK chaperone system. ClpB belongs to the family of AAA+ ATPases and
      forms ring-shaped oligomers: heptamers in the absence of nucleotides and hexamers
      in the presence of nucleotides. We investigated the thermodynamic stability of
      ClpB in its monomeric and oligomeric forms. ClpB contains six distinct structural
      domains: the N-terminal domain involved in substrate binding, two AAA+ ATP
      binding modules, each consisting of two domains, and a coiled-coil domain
      inserted between the AAA+ modules. We produced seven variants of ClpB, each
      containing a single Trp located in each of the ClpB domains and measured the
      changes in Trp fluorescence during the equilibrium urea-induced unfolding of
      ClpB. We found that two structural domains: the small domain of the C-terminal
      AAA+ module and the coiled-coil domain were destabilized in the oligomeric form
      of ClpB, which indicates that only those domains change their conformation and/or
      interactions during formation of the ClpB rings.

PMID- 16615935
TI  - Expression and activity of transglutaminase II in spontaneous tumours of dogs and
      cats.
AB  - Tissue transglutaminase II (TGase II) is a dual function protein with both
      transamidating and guanidine triphosphate (GTP)-binding capabilities. Previous
      studies have implicated TGase as a pro-apoptotic molecule; however, our recent
      findings indicate that TGase II may act as a survival factor in various cell
      types. The purpose of this study was to survey TGase II expression in normal
      tissue and spontaneous tumours of dogs and cats, by Western blotting and
      immunohistochemistry. Bladder, liver and adrenal gland exhibited prominent
      expression of TGase II while other tissues, including mammary gland, displayed
      limited expression and activity. TGase II GTP-binding in normal tissues was
      proportional to the level of expression in all tissues examined. Normal mammary
      tissue and that showing benign hyperplasia did not express TGase II. However,
      11/25 (44%) of canine mammary carcinomas and 10/12 (83%) of feline mammary
      carcinomas strongly expressed TGase II in either a stromal, cellular or combined
      pattern. The pattern of expression was not related to the classification of
      mammary carcinoma (solid, tubulopapillary, complex or anaplastic), except that
      two anaplastic canine mammary carcinomas showed prominent TGase II expression.
      Two canine mammary carcinoma cell lines showed prominent TGase expression, and
      when the TGase activity was inhibited, the cells became more sensitive to
      doxorubicin-induced cell death. Thus, TGase II was significantly expressed in
      mammary cancers from dogs and cats and immunoreactivity of TGase II was similar
      to that reported in humans beings. The pro-survival effect of TGase II in canine
      mammary carcinoma cell lines was similar to that previously reported in humans
      patients.

PMID- 16615936
TI  - Cryptosporidium infection in domestic geese (Anser anser f. domestica) detected
      by in-situ hybridization.
AB  - An in-situ hybridization (ISH) procedure was developed for the detection of
      Cryptosporidium sp. in paraffin wax-embedded tissues with a digoxigenin-labelled
      probe targeting the 18S rRNA. This technique was used in addition to traditional
      methods, such as haematoxylin and eosin staining, periodic acid-Schiff reaction,
      transmission electron microscopy and the polymerase chain reaction, to examine
      the bursa of Fabricius (BF), conjunctiva and other tissues from 20 domestic geese
      aged 16-36 days for the presence of cryptosporidia. Positive signals were found
      to a moderate or marked extent in both conjunctival samples (89%) and BF samples
      (88%) but not in other tissues. Sequencing of the PCR amplification product
      revealed identity with Cryptosporidium baileyi. The infected geese showed no
      clinical signs and only scanty histological lesions. These results confirm
      reports showing that young waterfowl are especially vulnerable to cryptosporidium
      infection and indicate that the BF and conjunctiva are the preferred sites for
      the presence of the protozoon. ISH proved a good method for detecting and
      identifying even small numbers of cryptosporidia in tissue sections.

PMID- 16615937
TI  - Natural cases of visna in sheep with myelitis as the sole lesion in the central
      nervous system.
AB  - Of 118 sheep with visna, 12 showed myelitis as the only nervous lesion. They were
      ovine lentivirus (OvLV)-seropositive and provirus DNA was demonstrated by LTR-PCR
      in all the samples with lesions. Clinically, all showed hindlimb paralysis and
      some were completely recumbent. Grossly, a swollen and discoloured area was
      identified in the white matter in 10 sheep. Microscopical changes consisted of a
      wedge-shaped area of non-suppurative leucomyelitis with mononuclear perivascular
      cuffing, demyelination and white matter degeneration. Except for two samples,
      grey matter was affected adjacent to severe white matter lesions. Three different
      microscopical patterns of lesion were identified, all having in common the
      presence of perivascular inflammation: the so-called vascular pattern was
      characterized by perivascular cuffs with minimal lesions in the adjacent
      neuroparenchyma; the malacic pattern, which was the commonest type, was
      characterized by severe white matter destruction and small numbers of
      macrophages; and the infiltrative pattern was characterized by a severe
      infiltrate of histiocytes in the parenchyma. Maedi-visna virus antigen was
      detected immunohistochemically only in areas with lesions, and the degree of
      immunolabelling was unrelated to the severity of the damage. Diagnosticians
      should bear in mind that a considerable number of visna cases show only spinal
      cord lesions. Examination of paraffin wax-embedded samples by LTR-PCR and
      immunohistochemistry would seem useful in confirming a histopathological
      diagnosis of visna from spinal cord samples.

PMID- 16615938
TI  - Multicentric malignant Schwannoma in a crossbred cow.
AB  - Multicentric malignant Schwannoma in a crossbred cow is described. Multiple and
      solitary nodules of varying sizes were seen to be distributed throughout the body
      of the animal, mainly along the peripheral nerves supplying the muscles of the
      thoracic and abdominal regions and the skin. Multiple nodules were also observed
      in the hilus of the liver. The mediastinal lymph nodes were replaced by a large
      solitary tumorous mass. Multiple neoplastic linear cords with small nodules were
      observed on the pericardium. Histologically, the nodules showed mainly densely
      packed, spindle-shaped cells arranged in short interwoven bundles and whorls
      (Antoni type A pattern). Stellate, spindle-shaped and round or oval tumour cells
      proliferated haphazardly within the loose texture of a collagenous matrix (Antoni
      type B pattern). Immunohistochemically, in both Antoni type A and type B areas,
      neoplastic cells reacted with antibodies against S-100 protein. Based on the
      metastasis of the tumour to the lymph nodes and on histology, the neoplasm was
      diagnosed as a multicentric malignant Schwannoma.

PMID- 16615950
TI  - Value of a community pediatrics rotation for residents.

PMID- 16615951
TI  - Cardiovascular support in the preterm: treatments in search of indications.

PMID- 16615952
TI  - Early postnatal administration of intravenous amino acids to preterm, extremely
      low birth weight infants.

PMID- 16615953
TI  - Ritonavir and fluticasone: beware of this potentially fatal combination.

PMID- 16615954
TI  - Hospitalists in children's hospitals: What we know now and what we need to know.

PMID- 16615955
TI  - Early provision of parenteral amino acids in extremely low birth weight infants:
      relation to growth and neurodevelopmental outcome.
AB  - OBJECTIVE: To determine if postnatal growth failure exerts an adverse effect on
      subsequent growth and neurodevelopment. STUDY DESIGN: A secondary analysis of
      1018 infants who were enrolled in a randomized, clinical trial of glutamine
      supplementation was performed to determine whether early provision of parenteral
      amino acids (AA) is associated with better growth and neurodevelopmental
      outcomes. Infants were stratified by whether they were provided > or =3 g/kg per
      day of AA at < or =5 days of life (early; n = 182) or not (late; n = 836).
      RESULTS: At 36 weeks' postmenstrual age, significant differences were found in
      weight, length, and head circumference in favor of the infants who received early
      AA; the odds of having weight less than the 10(th) percentile for age was 4-fold
      higher for infants in the late group. At 18 months' CA, there were no differences
      in weight, length, or measures of neurodevelopment between the groups; however,
      male infants in the late group were twice as likely to have head circumference
      less than the 10(th) percentile. CONCLUSIONS: Early AA were associated with
      significantly better growth outcomes at 36 weeks' postmenstrual age, and fewer
      infants who received early AA were found to have suboptimal head growth at 18
      months' CA.

PMID- 16615956
TI  - Pilot study of milrinone for low systemic blood flow in very preterm infants.
AB  - OBJECTIVES: To examine the hemodynamic effects of milrinone given
      prophylactically to very preterm infants at high risk of low superior vena cava
      (SVC) flow and to investigate the preliminary efficacy and safety of an optimal
      dose. STUDY DESIGN: This was a prospective, open-label study in two stages. The
      first involved dose escalation in two cohorts. Milrinone infusions of 0.25
      microg/kg per minute (n = 8) and then 0.5 microg/kg per minute (n = 11) were
      administered from 3 to 24 hours of age. Population pharmacokinetic modeling was
      used to develop an optimized dose regimen. Ten infants then were loaded with 0.75
      microg/kg per minute for 3 hours, followed by 0.2 microg/kg per minute
      maintenance until 18 hours of age. Infants were monitored for blood pressure,
      serial echocardiograms, and blood milrinone levels. The primary outcome was
      maintenance of SVC flow greater than 45 mL/kg per minute through the first 24
      hours. RESULTS: Low SVC flow developed in 36% of babies at both 0.25 microg/kg
      per minute and 0.5 microg/kg per minute of milrinone. Blood levels on these two
      regimens were slow to reach the target range and accumulated above this range by
      24 hours. At 0.75 to 0.2 microg/kg per minute, no infant had SVC flow below 45
      mL/kg per minute, compared with 61% in historic control subjects. Four infants
      needed an additional inotrope to support blood pressure. Blood levels were within
      the target range in 9 of 10 babies. CONCLUSIONS: We used population
      pharmacokinetic modeling to develop an optimal dosing regimen for milrinone. The
      efficacy and safety in this novel preventative approach to circulatory support is
      encouraging but inconclusive. We do not recommend the use of milrinone in preterm
      infants outside a research setting.

PMID- 16615957
TI  - Longitudinal influence of mother's child-feeding practices on adiposity in
      children.
AB  - OBJECTIVE: Parental child-feeding practices are potentially significant
      determinants of body weight in youth. To date, research has focused on white
      middle class mother-child dyads. This study examines the longitudinal influences
      of child-feeding practices with time on total fat mass in white and African
      American boys and girls. STUDY DESIGN: Seventy-four white children (49 girls, 25
      boys) and 47 African American children (25 girls, 22 boys; mean age at baseline,
      11.0 years) and their mothers participated in this study. Child-feeding practices
      were measured with the Child Feeding Questionnaire. Total fat mass was measured
      by means of Dual energy X-ray absorptiometry on a yearly basis. The average
      follow-up period was 2.7 years. RESULTS: Pressure to eat and concern for the
      child's weight in white participants and restriction and concern for the child's
      weight in African American participants were significantly related to total fat
      mass at baseline. Concern for the child's weight was negatively related to the
      change of total fat mass with time in white participants. No longitudinal effects
      of child feeding practices on the change of total fat mass were found in African
      American participants. CONCLUSION: Parental concern for weight is a predictor of
      change in total fat mass with time in white children, but not African American
      children.

PMID- 16615959
TI  - Left atrial diameters in overweight children with normal blood pressure.
AB  - OBJECTIVE: To measure left atrial (LA) diameter in normotensive, overweight
      children and to determine the variables that independently influence LA
      diameters. STUDY DESIGN: A cross-sectional study on 22 overweight children (age,
      13.40 +/- 1.22 years) and 18 control children (age, 13.40 +/- 2.19 years) was
      performed. LA diameter, left ventricular (LV) geometry, and LV systolic/diastolic
      function were measured through echocardiography. Data were compared between the
      two groups. Multiple regression analysis, with LA diameter as dependent variable,
      was conducted. RESULTS: In the overweight group, LV diastolic dimension, LV mass
      index, peak S, S/D ratio, Am, maximal LA diameter (34.1 mm vs 25.4 mm), middle LA
      diameter (26.9 mm vs 18.1 mm), and minimal LA diameter (22.5 mm vs 16.1 mm) were
      increased and Em/Am ratio was decreased. In multiple regression analysis, body
      mass index (R(2) = 0.7040, 0.7085, 0.7406 in respective maximal, middle, and
      minimal LA diameter) and systolic blood pressure (R(2) = 0.0540, 0.0477, 0.030 in
      respective maximal, middle, and minimal LA diameter) were significant independent
      correlates of all three measures of LA diameter. CONCLUSIONS: LA diameter in
      normotensive overweight children is increased. Body mass index and systolic blood
      pressure were significant correlates of LA diameter.

PMID- 16615961
TI  - Case-control study of symptoms and neonatal outcome of human milk-transmitted
      cytomegalovirus infection in premature infants.
AB  - OBJECTIVE: Preterm infants are at risk of acquiring human cytomegalovirus (CMV)
      infection through breast milk transmission, possibly leading to serious symptoms,
      as suggested by previous studies. Over a period of 8.5 years, we compared infants
      infected postnatally with CMV with noninfected controls to determine whether CMV
      infection transmitted through breast milk poses serious acute risks. STUDY
      DESIGN: CMV monitoring included maternal serologic testing and biweekly viral
      culture and polymerase chain reaction in breast milk and infant urine. Clinical
      and laboratory test findings were assessed retrospectively in infected infants
      and controls matched for gestational age during the initial hospital stay.
      RESULTS: Forty CMV-infected infants met the study criteria. They had lower
      minimal platelet and neutrophil counts and a higher frequency of C-reactive
      protein (CRP) elevations to 10 to 20 mg/L than their matched controls (P < or =
      .001). But no association of CMV infection with bronchopulmonary dysplasia,
      necrotizing enterocolitis, growth, or CRP elevations to > 20 mg/L was found.
      Cholestasis appeared in 3 infants in the CMV-infected group, but disappeared
      within 10 weeks. CONCLUSIONS: Neonatal symptoms related to postnatal CMV
      infection were transient and had no affect on neonatal outcome in these infants,
      in contrast with uncontrolled reports. Whether withholding or pasteurizing breast
      milk is warranted, however, depends on long-term outcome.

PMID- 16615962
TI  - Hearing loss in children with congenital cytomegalovirus infection born to
      mothers with preexisting immunity.
AB  - OBJECTIVE: To define hearing outcomes in children with congenital cytomegalovirus
      (CMV) infection born to mothers with non-primary CMV infection. STUDY DESIGN: A
      cohort of 300 children with congenital CMV infection identified by newborn
      virologic screening at the University of Alabama Hospital and a private community
      hospital in which the type of maternal infection could be classified constituted
      the study population. Maternal infections were categorized by analyzing serum
      samples. Children were followed prospectively and underwent serial audiologic
      evaluations. RESULTS: The frequency of hearing loss was not different between
      children born to mothers with non-primary infection (10%) and those with primary
      infection (11%). Significantly more children in the primary infection group had
      progressive and severe/profound hearing loss compared with children in the non
      primary group. The frequency of bilateral, delayed onset, high-frequency, and
      fluctuating hearing loss was not different between the 2 groups. The mean age of
      diagnosis of hearing loss was 39 +/- 53 months for children born to mothers with
      non-primary infection and 13 +/- 21 months for the primary infection group (P =
      .16). CONCLUSIONS: Maternal preexisting seroimmunity to CMV does not provide
      complete protection against hearing loss in infants with congenital CMV
      infection.

PMID- 16615963
TI  - Neural progenitors populate the cerebrospinal fluid of preterm patients with
      hydrocephalus.
AB  - OBJECTIVES: To evaluate cerebrospinal fluid (CSF) of preterm patients with
      hydrocephalus for neural progenitors. STUDY DESIGN: This report describes a
      prospective study of CSF obtained from preterm infants, either with progressive
      posthemorrhagic hydrocephalus (PPHH) or without known intercranial pathology.
      Cells recovered by centrifugation were analyzed by reverse transcriptase
      polymerase chain reaction or by immunocytometry. Alternatively, cells were
      cultured by using methods permissive to neural progenitor growth and analyzed by
      immunocytochemistry and Western blotting. RESULTS: Human CSF cells were obtained
      from 20 preterm infants at approximately 27 weeks estimated gestational age (15
      infants with PPHH, 5 control infants). The number of these cells removed over
      time from patients with PPHH were substantial, based on our calculations. Cells
      recovered from patients with PPHH transcribe markers for neural progenitors, all
      the mature cells types of the central nervous system, and a large battery of
      chondroitin sulfate proteoglycan genes, including the entire aggrecan/lectican
      family. These cells proliferated in culture, and precursor markers were detected
      by Western blotting, immunocytochemistry, and cytometry. Cells could not be
      cultured from control patients. CONCLUSIONS: Neural progenitor accumulation in
      CSF could confound the clinical interpretation of CSF cell counts in
      hydrocephalus and may play as yet undetermined roles in the biology of injury
      after hydrocephalus. These findings suggest the potential for neural stem cell
      propagation from CSF.

PMID- 16615964
TI  - Sociocultural factors that affect pregnancy outcomes in two dissimilar immigrant
      groups in the United States.
AB  - OBJECTIVE: To compare perinatal risks and outcomes in foreign- and U.S.-born
      Asian-Indian and Mexican women. STUDY DESIGN: We evaluated 6.4 million U.S. vital
      records for births during 1995-2000 to white, foreign- and U.S.-born Asian-Indian
      and Mexican women. Risks and outcomes were compared by use of chi2 and logistic
      regression. RESULTS: With the exception of increased teen pregnancy and tobacco
      use, the favorable sociodemographic profile and increased rate of adverse
      outcomes seen in foreign-born Asian Indians persisted in their U.S.-born
      counterparts. In contrast, foreign-born Mexicans had an adverse sociodemographic
      profile but a low incidence of low birth weight (LBW), whereas U.S.-born Mexicans
      had an improved sociodemographic profile and increased LBW, prematurity and
      neonatal death. CONCLUSIONS: Perinatal outcomes deteriorate in U.S.-born Mexican
      women. In contrast, the paradoxically increased incidence of LBW persists in U.S.
      born Asian-Indian women. Further research is needed to identify the social and
      biologic determinants of perinatal outcome.

PMID- 16615965
TI  - Rett syndrome in Australia: a review of the epidemiology.
AB  - OBJECTIVE: To examine the prevalence, cumulative incidence, and survival in an
      Australian cohort with Rett syndrome (RTT). STUDY DESIGN: The Australian Rett
      Syndrome Database is a longitudinal data collection that included 276 verified
      female cases at the end of 2004. Survival was calculated using the Kaplan-Meier
      product limit method, and cumulative incidence was determined using the
      complement of the Kaplan-Meier method. RESULTS: Most cases (88.4%) have had MECP2
      mutation testing, with positive results in 73%. The prevalence of RTT was .88 per
      10,000 females in 5- to 18-year-olds, and the cumulative incidence was 1.09 per
      10,000 females by 12 years of age. The cumulative incidence by the age of 5 years
      increased from .39 per 10,000 in the 1980 to 1984 cohort to .76 per 10,000 in
      birth cohorts beyond 1984. Survival was 77.8% at 25 years, compared with 99.96%
      survival in the Australian female population. Pneumonia (10/25) was the most
      common cause of death. CONCLUSIONS: The availability of genetic testing has
      contributed to the changing pattern and timing of RTT diagnosis in Australia.
      Girls with RTT have worse survival compared with the general female population.
      When more data are available, it will be possible to evaluate the relationship
      between survival and specific MECP2 mutations.

PMID- 16615966
TI  - The burden of hepatitis C virus infection in children: estimated direct medical
      costs over a 10-year period.
AB  - OBJECTIVE: To quantify the burden of pediatric hepatitis C virus (HCV) disease
      over the coming decade. STUDY DESIGN: Using national Census results and published
      and unpublished data, we constructed estimates of HCV prevalence, incidence, rate
      of vertical transmission, sustained viral response (SVR), and severe
      complications of infection. Using these figures, we generated a projection model
      for pediatric HCV outcomes, and we then performed a sensitivity analysis by
      altering the rates of fibrosis development and SVR. RESULTS: A prevalence of
      23,048 to 42,296 pediatric patients with chronic HCV combined with 7200 new cases
      from vertical transmission was used for further calculations. Over the next
      decade, estimated screening costs were 26 million US dollars, monitoring costs
      ranged from 117 million US dollars to 206 million US dollars, and treatment costs
      ranged from 56 million US dollars to 104 million US dollars. CONCLUSIONS: To
      date, pediatric HCV has received relatively little attention, but it will have a
      significant economic impact over the next 10 years if changes in practice are not
      made.

PMID- 16615967
TI  - The impact of pediatric trauma in the Amish community.
AB  - OBJECTIVE: To describe the epidemiology of trauma in Amish children and to
      determine differences in treatment and outcome related to injury mechanism. STUDY
      DESIGN: In this retrospective review, data were collected on all Amish children
      with trauma requiring hospital admission. Demographic, interventional, and
      outcome data were collected. Categorical outcomes were compared by using chi
      square, logistic regression, or Fisher exact test; continuous outcomes were
      compared with analysis of variance. RESULTS: A total of 135 trauma admissions
      were studied. There was a significant difference of proportion of injury by month
      (P < .01). The most common mechanisms of injury were falls (39%), buggy versus
      motor vehicle accidents (MVA; 16%), and animal injuries (14%). A total of 41% of
      patients required operative procedures, and 50% of subjects required intensive
      care. Animal injuries and buggy versus MVA were significantly associated with a
      requirement for surgery, increased length of stay, and increased severity (all P
      < .01). The overall mortality rate was 3%. There were significant associations
      between mechanism of injury and outcome scores (P < .05) and hospital charges (P
      < .05). CONCLUSIONS: The spectrum of traumatic injuries is unique among Amish
      children. These injuries contribute significantly to morbidity and mortality and
      impose a large monetary burden on the Amish community. Education may decrease the
      incidence of these events.

PMID- 16615969
TI  - Characteristics at diagnosis of type 1 diabetes in children younger than 6 years.
AB  - OBJECTIVE: To characterize the prodrome, presentation, family history, and
      biochemical status at diagnosis of type 1 diabetes mellitus (T1D) in children
      under age 6 years. STUDY DESIGN: This was a retrospective chart review of
      patients hospitalized at diagnosis with T1D from 1990 to 1999 in a children's
      hospital. RESULTS: A total of 247 children were hospitalized, 44% of whom
      presented in diabetic ketoacidosis (DKA). When stratified by 2-year age
      intervals, only total carbon dioxide (tCO(2)) was significantly lower in the
      youngest children (P = .02), and the duration of candidiasis was significantly
      longer in those children presenting in DKA (P = .004). Parents were more likely
      to recognize symptomatic hyperglycemia in children older than 2 years (P <
      .0001). Most parents sought care for their child suspecting that the child had
      diabetes; the other children were diagnosed when presenting with another concern.
      Only gender and tCO(2) were significantly correlated with hemoglobin A1c (HbA1c);
      age-adjusted HbA1c was 0.64% higher in girls compared with boys (P = .045), and
      each 1-mmol/L decrement in tCO(2) increased the age- and gender-adjusted HbA1c by
      0.086% (P < .001). CONCLUSIONS: A high proportion of children under age 6 years
      present critically ill at the diagnosis of T1D. When any of the classic symptoms
      of diabetes or a yeast infection is present, a serum glucose level should be
      measured.

PMID- 16615970
TI  - Prognostic value of plasma N-terminal pro-brain natriuretic peptide in children
      with congenital heart defects and open-heart surgery.
AB  - OBJECTIVE: To assess whether preoperative and postoperative plasma levels of N
      terminal pro-brain natriuretic peptide (NT-proBNP) predict postoperative outcome
      of open-heart surgery in children. STUDY DESIGN: A prospective observational
      study was conducted with 40 children with congenital heart defects who were
      undergoing elective open-heart surgery. Plasma levels of NT-proBNP, troponin T,
      lactate, C-reactive protein, and total neutrophil cell counts were measured
      before, during, and 1 and 3 hours after the end of cardiopulmonary bypass
      grafting (CPB). Outcomes were assessed by means of the kind, dosage, and duration
      of inotropic drug use during the postoperative period, lactate concentrations,
      and the duration of mechanical ventilation. RESULTS: Preoperative levels of NT
      proBNP were significantly increased irrespective of the type of congenital heart
      defect and the age of the patient. Preoperative NT-proBNP levels were higher in
      patients receiving prolonged postoperative inotropic drug therapy (r = 0.56, P =
      .0003). By means of multivariate analysis with the duration of inotropic therapy
      as the dependent variable, a significant impact of preoperative NT-proBNP levels,
      the presence of a cyanotic heart defect, the risk adjustment for congenital heart
      surgery score, duration of CPB time, and postoperative lactate levels were
      demonstrated (R squared = 76.8%, P <.0001). CONCLUSION: Preoperative NT-proBNP
      levels were associated with complicated postoperative outcome in children who
      underwent low-risk open-heart surgery. This marker may therefore be a useful tool
      in risk stratification of patients with congenital heart defects.

PMID- 16615971
TI  - Once-daily ciclesonide in children: efficacy and safety in asthma.
AB  - OBJECTIVE: To compare the efficacy and safety of once-daily inhaled ciclesonide
      40 mug (CIC40), 80 mug (CIC80), and 160 mug (CIC160) with placebo in children
      with persistent asthma of all severities. STUDY DESIGN: Overall, 1031 children
      age 4 to 11 years were randomized into 2 identical double-blinded, placebo
      controlled, parallel group studies consisting of a run-in phase followed by 12
      weeks of treatment. Both studies were designed to allow for a prespecified
      integrated analysis. The primary outcome variable was change in forced expiratory
      volume in 1 second (FEV(1)) percent predicted between baseline and study end;
      treatment comparisons were assessed using analysis of covariance. Additional
      endpoints included asthma symptom scores, daily albuterol use, and safety,
      including hypothalamic-pituitary-adrenal (HPA) axis function. RESULTS: Baseline
      characteristics were comparable; 59.4% of patients had moderate asthma, and 24.1%
      had severe asthma. All ciclesonide doses were associated with greater
      improvements in baseline to week 12 FEV(1) percent predicted versus placebo
      (CIC40, 11.97; CIC80, 13.58, P <.05; CIC160, 14.17, P < .01). Significant
      improvements in asthma symptoms (P < .01) and reductions in albuterol use were
      reported. Ciclesonide was well tolerated with no effect on HPA axis function.
      CONCLUSIONS: In this integrated analysis, ciclesonide was effective and well
      tolerated in children with persistent asthma.

PMID- 16615972
TI  - Pediatric workforce: a look at pediatric cardiology data from the American Board
      of Pediatrics.

PMID- 16615973
TI  - Cushing syndrome with secondary adrenal insufficiency from concomitant therapy
      with ritonavir and fluticasone.
AB  - We present 2 cases of Cushing syndrome with secondary adrenal insufficiency from
      concomitant use of ritonavir and inhaled corticosteroids in children with human
      immunodeficiency virus infection. These cases highlight the need for special
      consideration when treatment with an inhaled/intranasal corticosteroid is
      indicated in children receiving antiretroviral therapy.

PMID- 16615974
TI  - Failure to eradicate HIV despite fully successful HAART initiated in the first
      days of life.
AB  - Highly active antiretroviral therapy (HAART) started shortly after birth resulted
      in reversion of human immunodeficiency virus (HIV) plasma viremia, proviral DNA
      in PBMC, viral culture, and serum HIV antibodies to negative. Discontinuation of
      HAART 2 years after apparent HIV eradication, however, was followed by virus
      replication, CD4 decline, and destruction of HIV-specific lymphocytes,
      epitomizing the impossibility of HIV eradication.

PMID- 16615975
TI  - Down syndrome and complete tracheal rings.
AB  - Tracheal stenosis caused by complete tracheal rings has previously not been
      associated with Down syndrome. We identified 7 children with Down syndrome and
      complete tracheal rings. We found the clinical presentation and airway anatomy to
      be variable, advocating a heightened level of suspicion when evaluating a child
      with Down syndrome.

PMID- 16615976
TI  - Severe liver disease in early childhood due to fibrinogen storage and de novo
      gamma375Arg-->Trp gene mutation.
AB  - We report hypofibrinogenemia and massive hepatic storage of fibrinogen in a child
      with cryptogenic chronic liver disease. Fibrinogen gene analysis revealed a de
      novo Aguadilla (c.1201C>T; p.Arg375Trp) mutation. This mutation should be
      considered in childhood hypofibrinogenemia associated with chronic liver disease.

PMID- 16615977
TI  - Cerebral infarction after high-dose intravenous immunoglobulin therapy for
      Kawasaki disease.
AB  - A 3-year-old boy with Kawasaki disease developed a cerebral infarction after high
      dose intravenous immunoglobulin. Aspirin did not prevent the stroke. Based on the
      numerous reports of thrombosis due to high-dose immunoglobulin in older
      individuals, we conclude that it is necessary to be aware of this complication
      when treating children with Kawasaki disease.

PMID- 16615978
TI  - Effect of topical 1.25% povidone-iodine eyedrops used for prophylaxis of
      ophthalmia neonatorum on renal iodine excretion and thyroid-stimulating hormone
      level.
AB  - The 1% silver nitrate, which has been used for preventing gonococcal
      conjunctivitis in the neonate, is not effective against Chlamydia trachomatis and
      may provoke eye irritation. It is not known whether the alternative topical
      agent, 1.25% povidone-iodine, can influence thyroid function. In this study, no
      influence of povidone-iodine on thyroid function was observed.

PMID- 16615979
TI  - A novel form of non-X-linked hyperigm associated with growth and pubertal
      disturbances and with lymphoma development.
AB  - HyperIgM syndrome is a heterogenous immunodeficiency characterized by impaired
      class-switch recombination due to different molecular abnormalities. We report on
      two female patients affected by a novel syndrome associating HIGM, growth and
      pubertal disturbances, and severe lymphoid hyperplasia with eventual development
      into lymphomas, suggesting a DNA repair defect.

PMID- 16615980
TI  - Cutaneous leukocytoclastic vasculitis in a child with interleukin-12 receptor
      beta-1 deficiency.
AB  - We report a patient with complete interleukin-12 receptor beta-1 deficiency
      associated with cutaneous leukocytoclastic vasculitis. The patient experienced
      Bacille Calmette Guerin, Mycobacterium chelonae, and Salmonella enteritidis
      infection. Vasculitis affecting both small arteries and postcapillary venules due
      to deposition of immune complexes was probably caused by S. enteritidis and/or M.
      chelonae infection.

PMID- 16615981
TI  - Phenotypic spectrum of CHARGE syndrome with CHD7 mutations.
AB  - CHD7 gene mutations were identified in 17 (71%) of 24 children clinically
      diagnosed to have CHARGE syndrome (C, coloboma of the iris or retina; H, heart
      defects; A, atresia of the choanae; R, retardation of growth and/or development;
      G, genital anomalies; and E, ear abnormalities). Colobomata, hearing loss,
      laryngomalacia, and vestibulo-cochlear defect were prevalent. Molecular testing
      for CHD7 enables an accurate diagnosis and provides health anticipatory guidance
      and genetic counseling to families with CHARGE syndrome.

PMID- 16615982
TI  - Hallermann-Streiff syndrome: those are not supernumerary teeth.

PMID- 16615984
TI  - The egg or the chicken? Should good compliance to multi-injection insulin therapy
      be a criterion for insulin pump therapy, or does insulin pump therapy improve
      compliance?

PMID- 16615986
TI  - Testicular microlithiasis and McCune-Albright syndrome.

PMID- 16615987
TI  - Rituximab for chronic immune thrombocytopenic purpura.

PMID- 16615988
TI  - Chronic immune thrombocytopentic purpura in children: assessment of rituximab
      treatment.

PMID- 16615990
TI  - Morphometric study of length and grooves of maxillary lateral incisor roots.
AB  - OBJECTIVE: Root grooves are considered a risk factor for periodontal disease. The
      purpose of this study was to measure the length of the root of maxillary lateral
      incisors (MLI), as well as the width and depth of the concavities of their
      proximal surfaces, and also to determine the prevalence of palato-gingival
      grooves. METHODS: the width and depth of root concavities, as well as root length
      were evaluated in 73 MLI. All teeth were measured using a digital contour
      measuring instrument for the root grooves and a caliper for evaluating root
      length. RESULTS: After statistical analysis (p<0.05) it was possible to confirm:
      the mean root length on its mesial surface was (15.47+/-1.72 mm), on its distal
      surface (14.99+/-1.70 mm), on its buccal surface (13.10+/-1.69 mm) and on its
      lingual surface (12.71+/-1.53 mm); concavities were present in 100% of the
      samples; concavities were found 2mm, coronally from the CEJ, at the CEJ, and
      apically up to 8mm; the concavities were wider than deeper; on the mesial
      surface, the greatest width was (1.05 mm) and the greatest depth was (0.06 mm)
      both at the CEJ; 5) on the distal surface the greatest width was (0.73 mm) at 6mm
      apically from the CEJ and the greatest depth was (0.003 mm); the palato-gingival
      groove was observed in 9.58% of the samples. CONCLUSIONS: The mesial surface of
      the maxillary lateral incisor is the longest. The root concavities on the
      proximal surfaces are present in 100%. One must get acquainted to the
      morphological variations of roots to enhance diagnosis and treatment.

PMID- 16615991
TI  - Identification and neuropeptide content of trigeminal neurons innervating the rat
      gingivomucosal tissue.
AB  - OBJECTIVES: The purpose of this study was to identify and characterise the
      neuropeptide content and the size of trigeminal ganglion (TG) neurons innervating
      the rat gingivomucosal tissue. DESIGN: Retrograde nerve tracer Fluorogold (FG)
      was injected into the gingiva (group 1, n=5) or applied into the gingival sulcus
      (group 2, n=5) of the first right maxillary molar. After 10 days, the ganglia
      were dissected and FG fluorescence was observed under UV light microscope.
      Expression of calcitonin gene-related peptide (CGRP) and substance P (SP) in FG
      labelled neurons was investigated by immunohistochemistry. Cross-sectional areas
      of neuron cell bodies containing FG were determined. As a control group,
      approximately 1000 neuron cell bodies representing the entire TG neuron
      population was evaluated in five trigeminal ganglia. RESULTS: In group 1, the
      percentages of neurons containing CGRP (median 63%, range 48-72%) and SP (median
      64%, range 54-64%) were significantly greater than in the control group (CGRP:
      median 43%, range 42-47% and SP: median 23%, range 21-27%). In group 2, only the
      percentage of neurons containing SP (median 50%, range 40-56%) was significantly
      greater than in the control group. FG-labelled neurons were predominantly small
      or medium sized (less than 1200 microm2). The neurons in the group 1 were
      significantly smaller than in group 2. In both experimental groups,
      immunopositive neurons were significantly smaller than immunonegative neurons.
      CONCLUSIONS: The majority of neurons in TG that innervate the rat gingivomucosa
      are small or medium sized and contain CGRP and SP.

PMID- 16615992
TI  - Mitochondrial metabolic states regulate nitric oxide and hydrogen peroxide
      diffusion to the cytosol.
AB  - Mitochondria isolated from rat heart, liver, kidney and brain (respiratory
      control 4.0-6.5) release NO and H2O2 at rates that depend on the mitochondrial
      metabolic state: releases are higher in state 4, about 1.7-2.0 times for NO and 4
      16 times for H2O2, than in state 3. NO release in rat liver mitochondria showed
      an exponential dependence on membrane potential in the range 55 to 180 mV, as
      determined by Rh-123 fluorescence. A similar behavior was reported for
      mitochondrial H2O2 production by [S.S. Korshunov, V.P. Skulachev, A.A. Starkov,
      High protonic potential actuates a mechanism of production of reactive oxygen
      species in mitochondria. FEBS Lett. 416 (1997) 15_18.]. Transition from state 4
      to state 3 of brain cortex mitochondria was associated to a decrease in NO
      release (50%) and in membrane potential (24-53%), this latter determined by flow
      cytometry and DiOC6 and JC-1 fluorescence. The fraction of cytosolic NO provided
      by diffusion from mitochondria was 61% in heart, 47% in liver, 30% in kidney, and
      18% in brain. The data supports the speculation that NO and H2O2 report a high
      mitochondrial energy charge to the cytosol. Regulation of mtNOS activity by
      membrane potential makes mtNOS a regulable enzyme that in turn regulates
      mitochondrial O2 uptake and H2O2 production.

PMID- 16615993
TI  - Mode of action of the new antibiotic for Gram-positive pathogens daptomycin:
      comparison with cationic antimicrobial peptides and lipopeptides.
AB  - With the steady rise in the number of antibiotic-resistant Gram-positive
      pathogens, it has become increasingly important to find new antibacterial agents
      which are highly active and have novel and diversified mechanisms of action. Two
      classes will be discussed here: the cationic antimicrobial peptides, which are
      amphiphilic in nature, targeting membranes and increasing their permeability; and
      lipopeptides, which consist of linear or cyclic peptides with an N-terminus that
      is acylated with a fatty acid side chain. One member of the cyclic lipopeptide
      family, the anionic molecule daptomycin, has been extensively studied and is the
      major focus of this review. Models will be presented on its mode of action and
      comparisons will be made to the known modes of action of cationic antimicrobial
      peptides and other lipopeptides.

PMID- 16615994
TI  - Tumor necrosis factor-alpha inhibits the cardiac delayed rectifier K current via
      the asphingomyelin pathway.
AB  - Tumor necrosis factor-alpha (TNF-alpha) affects contractility and ionic currents
      in the heart. However, the electrophysiological effects, especially on delayed
      rectifier K currents (IK), have not yet been fully elucidated. We examined the
      effects of TNF-alpha on IK. Using a voltage-clamp method, IK was measured in
      guinea pig ventricular myocytes in the basal state and after pharmacological
      intervention. To specify the site of the action of TNF-alpha, the myocytes were
      incubated with pertussis toxin or N-oleoylethanolamine, a ceramidase inhibitor,
      and IK was measured. TNF-alpha suppressed IK when it was enhanced by
      isoproterenol, histamine or forskolin but not in the basal state or when IK was
      augmented by an internal application of cyclic AMP. Both pre-incubation with
      pertussis toxin and N-oleoylethanolamine abolished the inhibitory action of TNF
      alpha on isoproterenol-augmented IK. TNF-alpha inhibits IK, mainly IKs, when it
      is augmented by PKA as a result of the generation of sphingosine.

PMID- 16615995
TI  - Monochloramine potently inhibits arachidonic acid metabolism in rat platelets.
AB  - In the present study, the effects of hypochlorous acid (HOCl), monochloramine
      (NH(2)Cl), glutamine-chloramine (Glu-Cl) and taurine-chloramine (Tau-Cl) on the
      formation of 12-lipoxygenase (LOX) metabolite, 12-HETE, and cyclooxygenase (COX)
      metabolites, TXB(2), and 12-HHT, from exogenous arachidonic acid (AA) in rat
      platelets were examined. Rat platelets (4x10(8)/ml) were preincubated with drugs
      for 5min at 37 degrees C prior to the incubation with AA (40microM) for 2min at
      37 degrees C. HOCl (50-250microM) showed an inhibition on the formation of LOX
      metabolite (12-HETE, 5-67% inhibition) and COX metabolites (TXB(2), 33-73%
      inhibition; 12-HHT, 27-74% inhibition). Although Tau-Cl and Glu-Cl up to
      100microM were without effect on the formation of 12-HETE, TXB(2) and 12-HTT,
      NH(2)Cl showed a strong inhibition on the formation of all three metabolites (10
      100microM NH(2)Cl, 12-HETE, 21-92% inhibition; TXB(2), 58-94% inhibition; 12-HHT,
      36-92% inhibition). Methionine reversed a reduction of formation of LOX and COX
      metabolites induced by NH(2)Cl, and taurine restoring that induced by both
      NH(2)Cl and HOCl. These results suggest that NH(2)Cl is a more potent inhibitor
      of COX and LOX pathways in platelets than HOCl, and taurine and methionine can be
      modulators of NH(2)Cl-induced alterations in the COX and LOX pathways in vivo.

PMID- 16615996
TI  - A single amino acid substitution (R441A) in the receptor-binding domain of SARS
      coronavirus spike protein disrupts the antigenic structure and binding activity.
AB  - The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV)
      has two major functions: interacting with the receptor to mediate virus entry and
      inducing protective immunity. Coincidently, the receptor-binding domain (RBD,
      residues 318-510) of SAR-CoV S protein is a major antigenic site to induce
      neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the
      RBD and human IgG1 Fc, as a model in the studies and found that a single amino
      acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to
      induce neutralizing antibodies in immunized mice and rabbits. With a panel of
      anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt
      the majority of neutralizing epitopes in the RBD, suggesting that this residue is
      critical for the antigenic structure responsible for inducing protective immune
      responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not
      bind to soluble and cell-associated angiotensin-converting enzyme 2 (ACE2), the
      functional receptor for SARS-CoV and failed to block S protein-mediated
      pseudovirus entry, indicating that this point mutation also disrupted the
      receptor-binding motif (RBM) in the RBD. Taken together, these data provide
      direct evidence to show that a single amino acid residue at key position in the
      RBD can determine the major function of SARS-CoV S protein and imply for
      designing SARS vaccines and therapeutics.

PMID- 16615997
TI  - 1-Deoxymannojirimycin, the alpha1,2-mannosidase inhibitor, induced cellular
      endoplasmic reticulum stress in human hepatocarcinoma cell 7721.
AB  - Alpha1,2-mannosidases, key enzymes in N-glycan processing and located both in the
      endoplasmic reticulum and golgi, have been targets in the development of anti
      cancer therapies. Previous studies have shown its involvement in protein
      degradation. In this study, 1-deoxymannojirimycin, a specific inhibitor of
      alpha1,2-mannosidase and generating 'high mannose' type of N-glycan, was treated
      in human hepatocarcinoma 7721 cells and induced the endoplasmic reticulum stress.
      Key moleculars as XBP1 and GRP78/Bip were activated and up-regulated, which
      suggested the UPR pathway was activated. The cleavage of caspase-12, -9, and -3
      was also detected, which implicated the ER stress was triggered and apoptosis
      occurred in H7721 cells. The results indicate the 'high Man' structure generated
      by 1-deoxymannojirimycin may constitute potential novel mechanism for ER stress
      and caspase-12 pathway of cell apoptosis.

PMID- 16615998
TI  - Postnatal expression of KLF12 in the inner medullary collecting ducts of kidney
      and its trans-activation of UT-A1 urea transporter promoter.
AB  - Maturation of the inner medulla of the kidney occurs after birth and is vital for
      mammals to acquire maximal urinary concentrating ability. During this process,
      expression of several kidney transporters and channels involved in urine
      concentrating mechanisms is known to be regulated. We previously isolated KLF15
      as a transcription factor that regulates the expression of the ClC-K1 chloride
      channel. We have now found that another KLF transcription factor, KLF12, is
      expressed in the kidney from around 15 days after birth. To gain insight into its
      involvement in the maturation process of the inner medulla, we first determined
      the expression site of KLF12 within the kidney by in situ hybridization. By
      comparing the AQP2 immunolocalization in sequential sections, KLF12 was found to
      be expressed in the collecting ducts. Because expression of the urea transporter
      UT-A1 and amiloride-sensitive epithelial sodium channels ENaC is known to be
      tightly regulated in the collecting ducts after birth, we tested whether KLF12
      has a regulatory role in the promoter activities of these genes. KLF12 is able to
      increase UT-A1 but not ENaC promoter activity through the binding to CACCC motif.
      These results suggest that KLF12 is involved in the maturation processes of
      collecting ducts after birth, and that UT-A1 is a target gene of KLF12.

PMID- 16615999
TI  - Induced fit of passenger proteins fused to Archaea maltose binding proteins.
AB  - Maltose binding proteins (MBPs) are used as carriers for improving the solubility
      of passenger proteins. Our results indicate that the higher solubility of the
      fusions correlates with their elevated heat stability. Fusions of the otherwise
      thermo-sensitive GFP with MBPs from Archaea, but not GST-GFP and Escherichia coli
      MBP-GFP, maintained their fluorescence and structure after 10min incubation at
      100 degrees C and could be purified by heating the bacteria lysate, with yields
      even higher than those obtained using metal affinity chromatography. Furthermore,
      only correctly folded proteins could stand the heating treatment and, therefore,
      the heat-purification method can be used as a quality control step to select
      homogeneous monodispersed material whereas soluble aggregates are removed by
      precipitation.

PMID- 16616000
TI  - The effect of the mtDNA4834 deletion on hearing.
AB  - Mutations in mitochondrial DNA (mtDNA) are associated with diverse pathological
      states in humans, notably sensorineural deafness. In humans, mtDNA4977 deletion,
      known as common deletion, is thought to play a critical role in presbyacusis. A
      similar mtDNA deletion occurs in the naturally aging rats is mtDNA4834 deletion.
      Today, it is still obscure about the effect of common mtDNA deletion on the
      presbyacusis and hearing loss. We establish a model of rat associated with
      mtDNA4834 deletion in inner ear by d-galactose. It was found that the
      malondialdehyde (MDA) increased with superoxide dismutase (SOD) decreasing in the
      inner ear of the rat treated with d-galactose than of the control. However, there
      was no significant difference in elevation of ABR threshold between the rat with
      mtDNA4834 deletion induced by d-galactose and control. After aminoglycoside
      antibiotic injected, the hearing threshold of the rats carrying mtDNA4834
      deletion increased significantly compared with the rats without mtDNA4834
      deletion. The results show that resembled accelerated aging in the inner ear of
      the rat could be induced by injecting d-galactose. Moreover, those suggest that
      mtDNA4834 deletion can not directly induce the hearing loss, but acting as a
      predisposing factor which can greatly enhance the sensitivity of the inner ear to
      the aminoglycoside antibiotic.

PMID- 16616001
TI  - Antisense regulation of expression and transactivation functions of the
      tumorigenic HBx and c-myc genes.
AB  - Earlier we have shown that the X-myc transgenic mice develop hepatocellular
      carcinoma (HCC) due to co-expression of c-Myc and HBx protein of hepatitis B
      virus [R. Lakhtakia, V. Kumar, H. Reddi, M. Mathur, S. Dattagupta, S.K. Panda,
      Hepatocellular carcinoma in a hepatitis B 'x' transgenic mouse model: a
      sequential pathological evaluation. J. Gastroenterol. Hepatol. 18 (2003) 80-91].
      With the aim to develop therapeutic strategies for HCC, we constructed several
      mono- and bicistronic antisense recombinants against HBx and c-myc genes to
      regulate their expression as well as transactivation function in a human hepatoma
      cell line. A dose-dependent inhibition in the expression levels of HBx and c-Myc
      was observed with monocistronic constructs. Likewise, the bicistronic
      recombinants also blocked the expression as well as transactivation functions of
      cognate genes with equal efficacy. Further, expression of the constituent genes
      from the X-myc transgene could also be inhibited by these antisense constructs in
      cell culture. Thus, our study points towards clinical implications of antisense
      regulation of tumor-promoting genes in the management of HCC.

PMID- 16616002
TI  - Gap junctions modulate apoptosis and colony growth of human embryonic stem cells
      maintained in a serum-free system.
AB  - We investigated the gap junctional properties of human embryonic stem cells
      (hESC) cultivated in a serum-free system using sphingosine-1-phosphate and
      platelet-derived growth factor (S1P/PDGF). We compared this condition to hESC
      grown on Matrigel in mouse embryonic fibroblast conditioned medium (MEF-CM) or
      unconditioned medium (UM). We show that in all culture systems, hESC express
      connexins 43 and 45. hESC maintained in S1P/PDGF conditions and hESC grown in
      presence of MEF-CM are coupled through gap junctions while hESC maintained on
      Matrigel in UM do not exhibit gap junctional intercellular communication. In this
      latter condition, coupling was retrieved by addition of noggin, suggesting that
      BMP-like activity in UM inhibits gap junctional communication. Last, our data
      indicate that the closure of gap junctions by the decoupling agent alpha
      glycyrrhetinic acid increases cell apoptosis and inhibits hESC colony growth.
      Altogether, these results suggest that gap junctions play an important role in
      hESC maintenance.

PMID- 16616003
TI  - Identification of four evolutionarily related G protein-coupled receptors from
      the malaria mosquito Anopheles gambiae.
AB  - The mosquito Anopheles gambiae is an important vector for malaria, which is one
      of the most serious human parasitic diseases in the world, causing up to 2.7
      million deaths yearly. To contribute to our understanding of A. gambiae and to
      the transmission of malaria, we have now cloned four evolutionarily related G
      protein-coupled receptors (GPCRs) from this mosquito and expressed them in
      Chinese hamster ovary cells. After screening of a library of thirty-three insect
      or other invertebrate neuropeptides and eight biogenic amines, we could identify
      (de-orphanize) three of these GPCRs as: an adipokinetic hormone (AKH) receptor
      (EC(50) for A. gambiae AKH, 3x10(-9)M), a corazonin receptor (EC(50) for A.
      gambiae corazonin, 4x10(-9)M), and a crustacean cardioactive peptide (CCAP)
      receptor (EC(50) for A. gambiae CCAP, 1x10(-9)M). The fourth GPCR remained an
      orphan, although its close evolutionary relationship to the A. gambiae and other
      insect AKH receptors suggested that it is a receptor for an AKH-like peptide.
      This is the first published report on evolutionarily related AKH, corazonin, and
      CCAP receptors in mosquitoes.

PMID- 16616004
TI  - A novel hypothesis for the binding mode of HERG channel blockers.
AB  - We present a new docking model for HERG channel blockade. Our new model suggests
      three key interactions such that (1) a protonated nitrogen of the channel blocker
      forms a hydrogen bond with the carbonyl oxygen of HERG residue T623; (2) an
      aromatic moiety of the channel blocker makes a pi-pi interaction with the
      aromatic ring of HERG residue Y652; and (3) a hydrophobic group of the channel
      blocker forms a hydrophobic interaction with the benzene ring of HERG residue
      F656. The previous model assumes two interactions such that (1) a protonated
      nitrogen of the channel blocker forms a cation-pi interaction with the aromatic
      ring of HERG residue Y652; and (2) a hydrophobic group of the channel blocker
      forms a hydrophobic interaction with the benzene ring of HERG residue F656. To
      test these models, we classified 69 known HERG channel blockers into eight
      binding types based on their plausible binding modes, and further categorized
      them into two groups based on the number of interactions our model would predict
      with the HERG channel (two or three). We then compared the pIC(50) value
      distributions between these two groups. If the old hypothesis is correct, the
      distributions should not differ between the two groups (i.e., both groups show
      only two binding interactions). If our novel hypothesis is correct, the
      distributions should differ between Groups 1 and 2. Consistent with our
      hypothesis, the two groups differed with regard to pIC(50), and the group having
      more predicted interactions with the HERG channel had a higher mean pIC(50)
      value. Although additional work will be required to further validate our
      hypothesis, this improved understanding of the HERG channel blocker binding mode
      may help promote the development of in silico predictions methods for identifying
      potential HERG channel blockers.

PMID- 16616005
TI  - Requirement of nuclear localization and transcriptional activity of p53 for its
      targeting to the yolk syncytial layer (YSL) nuclei in zebrafish embryo and its
      use for apoptosis assay.
AB  - We expressed zebrafish p53 protein fused to GFP by a neuron-specific HuC promoter
      in zebrafish embryos. Instead of displaying neuronal expression patterns, p53-GFP
      was targeted to zebrafish YSL nuclei. This YSL targeting is p53 sequence-specific
      because GFP fusion proteins of p63 and p73 displayed neuronal-specific patterns.
      To dissect the underlying mechanisms, various constructs encoding a series of p53
      mutant proteins under the control of different promoters were generated. Our
      results showed that expression of p53, in early zebrafish embryo, is
      preferentially targeted to the nuclei of YSL, which is mediated by importin.
      Similarly, this targeting is abrogated when p53 nuclear localization signal is
      disrupted. In addition, the transcriptional activity of p53 is required for this
      targeting. We further showed that fusion of pro-apoptotic BAD protein to p53-GFP
      led to apoptosis of YSL cells, and subsequent imperfect microtubule formation and
      abnormal blastomere movements.

PMID- 16616006
TI  - Induction of SOCS-3 is insufficient to confer IRS-1 protein degradation in 3T3-L1
      adipocytes.
AB  - Insulin receptor substrate (IRS)-1 is a key protein in insulin signaling. Several
      studies have shown that the expression of IRS-1 can be modulated by protein
      degradation via the proteasome and the degradation of IRS-1 can be related to
      insulin-resistant states. The degradation of IRS-1 has been shown to be induced
      by SOCS-1 and SOCS-3 via the ubiquitin pathway. The goal of our study was to
      determine if the induction of SOCS-3 correlated with increased IRS-1 degradation
      in cultured 3T3-L1 adipocytes. Interestingly, our studies have shown that there
      is little correlation between the induction in SOCS-3 expression and the
      degradation of IRS-1 in mature 3T3-L1 adipocytes. Our results clearly demonstrate
      that treatment with leukemia inhibitory factor (LIF) or cardiotrophin (CT)-1
      strongly induces the expression of SOCS-3 in mature 3T3-L1 adipocytes, but does
      not affect the degradation of IRS-1. On the contrary, tumor necrosis factor (TNF)
      alpha and insulin, which very weakly induce SOCS-3 expression, have profound
      effects on IRS-1 degradation. In summary, our results indicate that the
      expression of SOCS-3 does not correlate with the degradation of IRS-1 proteins in
      fat cells.

PMID- 16616007
TI  - Precursor structure of egg proteins in the coral Galaxea fascicularis.
AB  - In the egg of the reef coral Galaxea fascicularis, four proteins (named GfEP-1 to
      -4) are stored in high abundance. In the present study, a cDNA containing a full
      length open reading frame for GfEP-1 was cloned, and the translated protein
      sequence was compared to the N-terminal sequences of GfEP-2, -3, and -4. GfEP-1
      and -2 were shown to be generated by processing of a precursor of 1439 amino
      acids, and GfEP-3 turned out to be a partial fragment of GfEP-2. The precursor
      protein contained regions which exhibited similarities to vitellogenins (Vgs) in
      bilaterian animals (oviparous vertebrates and invertebrates including nematodes,
      arthropods, and molluscs). This study reports the first cloning and
      characterization of a full-length cDNA encoding a Vg in a non-bilaterian animal,
      and argues that the emergence of Vg as a precursor of egg yolk proteins predated
      the divergence of the cnidarian and bilaterian lineages.

PMID- 16616008
TI  - Specific human CYP 450 isoform metabolism of a pentachlorobiphenyl (PCB-IUPAC#
      101).
AB  - Polychlorinated biphenyl IUPAC# 101-PCB 101 (chlorination pattern-2,2',4',5,5')
      is a common, persistent non-coplanar PCB congener found in the ambient
      environment but information related to its metabolism in humans is lacking.
      Previous studies indicate PCB 101 is rapidly metabolized in mammals through CYP
      2B and 3A family enzymes. Recently, PCB metabolism through a 2A family isoform in
      hamsters was also reported. To specifically identify the human CYP 450 isoforms
      responsible for PCB 101 metabolism, we compared human microsome metabolism to
      metabolism using several specific recombinant human CYP isoforms. These data
      characterized selective and extensive metabolism by human CYP 2A6. The product
      formed was the 4-hydroxy-PCB 101 metabolite (4-hydroxy-2,2',4',5,5') and was the
      only major metabolite observed in the recombinant and human microsome
      investigation. This is important information for predicting human specific
      toxicokinetics of PCBs.

PMID- 16616009
TI  - Lignan compounds and 4,4'-dihydroxybiphenyl protect C2C12 cells against damage
      from oxidative stress.
AB  - Lignan compounds are known to have various biological activities, especially
      antioxidative effects. We investigated whether lignan compounds show
      antioxidative activity in myoblast C2C12 cells. Among 14 lignan compounds
      investigated, two lignans containing two phenolic functional groups, namely
      Gomisin J and GR-12, prevented hydrogen peroxide (H(2)O(2))-induced cell death. A
      simple compound, 4,4'-dihydroxybiphenyl, which was found to be a common component
      of Gomisin J and GR-12, also largely prevented H(2)O(2)-induced cell death and
      almost completely prevented H(2)O(2)-induced increases in p38 MAPK
      phosphorylation. Our present results provide a useful in vitro system for
      clarifying the molecular mechanisms of lignan-mediated antioxidative effects and
      evaluating lead molecules toward the development of therapeutic drugs.

PMID- 16616010
TI  - Substrate specificity of archaeon Sulfolobus tokodaii biotin protein ligase.
AB  - Biotin protein ligase (BPL) is an enzyme mediating biotinylation of a specific
      lysine residue of the carboxyl carrier protein (BCCP) of biotin-dependent
      enzymes. We recently found that the substrate specificity of BPL from archaeon
      Sulfolobus tokodaii is totally different from those of many other organisms, in
      reflection of a difference in the local sequence of BCCP surrounding the
      canonical lysine residue. There is a conserved glycine residue in the biotin
      binding site of Escherichia coli BPL, but this residue is replaced with alanine
      in S. tokodaii BPL. To test the notion that this substitution dictates the
      substrate specificity of the latter enzyme, this residue, Ala-43, was converted
      to glycine. The K(m) values of the resulting mutant, A43G, for substrates, were
      smaller than those of the wild type, suggesting that the residue in position 43
      of BPL plays an important role in substrate binding.

PMID- 16616011
TI  - A unique mechanism for the processive movement of single-headed myosin-IX.
AB  - It has been puzzled that in spite of its single-headed structure, myosin-IX shows
      the typical character of processive motor in multi-molecule in vitro motility
      assay, because this cannot be explained by hand-over-hand mechanism of the two
      headed processive myosins. Here, we show direct evidence of the processive
      movement of myosin-IX using two different single molecule techniques. Using
      optical trap nanometry, we found that myosin-IX takes several large (
      approximately 20nm) steps before detaching from an actin filament. Furthermore,
      we directly visualized the single myosin-IX molecules moving on actin filaments
      for several hundred nanometers without dissociating from actin filament. Since
      myosin-IX processively moves without anchoring the neck domain, the result
      suggests that the neck tilting is not involved for the processive movement of
      myosin-IX. We propose that the myosin-IX head moves processively along an actin
      filament like an inchworm via a unique long and positively charged insertion in
      the loop 2 region of the head.

PMID- 16616012
TI  - Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after
      exercise, and heart rate variability in men with healed myocardial infarctions
      and depressed ejection fractions.
AB  - We explored possible mechanisms by which recommended intakes of omega-3 fatty
      acids may decrease the risk for sudden cardiac death in patients with documented
      coronary heart disease. The cardioprotective effects of omega-3 fatty acids have
      been documented in epidemiologic and randomized controlled trials. These fatty
      acids are presumed to decrease susceptibility to fatal arrhythmias, but whether
      this is mediated by classic risk factors or direct cardiac mechanisms is not
      known. Eighteen white men with a history of myocardial infarction and ejection
      fractions <40% were randomized to placebo or omega-3 fatty acids (585 mg of
      docosahexaenoic acid and 225 mg of eicosapentaenoic acid) for two 4-month periods
      in a crossover design. At the end of each period, heart rate (HR), HR
      variability, and rate of HR recovery after exercise were determined, as were
      effects on arterial compliance, blood pressure, cardiac function, and fasting
      serum levels of lipids and inflammatory markers. Omega-3 fatty acids decreased HR
      at rest from 73 +/- 13 to 68 +/- 13 beats/min (p <0.0001) and improved 1-minute
      HR recovery after exercise (-27 +/- 10 to -32 +/- 12 beats/min, p <0.01). HR
      variability in the high-frequency band increased (p <0.02), but no change was
      noted in overall HR variability. There were no significant effects on blood
      pressure, arterial compliance, lipids, or inflammatory markers. These changes are
      consistent with an increase in vagal activity and may in part explain the
      observed decrease in risk for sudden cardiac death seen with omega-3 fatty acid
      supplementation.

PMID- 16616013
TI  - Time course of microvascular resistance of the infarct and noninfarct coronary
      artery following an anterior wall acute myocardial infarction.
AB  - Previous studies have suggested that coronary flow velocity reserve (CFVR) in the
      early phase of acute myocardial infarction (AMI) is abnormal in infarcted and
      remote regions. This study determined the coronary microvascular resistance of
      infarct-related arteries (IRAs) and non-IRAs during AMI and at follow-up in
      patients who were treated with primary percutaneous intervention. In 73 patients
      with a first anterior wall AMI, baseline and minimal microvascular resistance in
      IRAs and non-IRAs immediately after reperfusion and at 1-week and 6-month follow
      up were calculated as the ratio of mean transvascular pressure gradient to mean
      baseline and to adenosine-induced hyperemic blood flow velocity, respectively.
      CFVR in IRAs increased from 1.6 +/- 0.4 after reperfusion to 1.9 +/- 0.5 at 1
      week and to 3.0 +/- 0.8 at 6 months (p <0.0001) and in non-IRAs from 2.4 +/- 0.5
      to 2.7 +/- 0.6 at 1 week to 3.3 +/- 0.6 at 6 months (p <0.0001). Minimal
      microvascular resistance in IRAs and non-IRAs (3.2 +/- 1.7 and 2.2 +/- 0.6 mm
      Hg/second/cm, respectively) decreased significantly at follow-up (2.0 +/- 0.6 and
      1.7 +/- 0.6 mm Hg/second/cm at 1 week and 1.8 +/- 0.6 and 1.8 +/- 0.7 mm
      Hg/second/cm at 6 months, respectively). After correction for rate-pressure
      product, baseline microvascular resistance after reperfusion and at 6 months did
      not significantly differ between IRAs and non-IRAs. In conclusion, minimal
      microvascular resistance is higher in infarcted and noninfarcted regions during
      AMI than at follow-up. The low CFVR in remote regions during AMI is probably due
      more to disturbed autoregulation than to increased myocardial workload.

PMID- 16616014
TI  - Effect of coronary occlusion site on angiographic and clinical outcome in acute
      myocardial infarction patients treated with early coronary intervention.
AB  - In acute myocardial infarction that is treated with thrombolysis, proximal
      coronary artery occlusion is associated with worse prognosis, irrespective of the
      infarcted artery. Primary percutaneous coronary intervention (PCI) is currently
      the treatment of choice for ST-segment elevation acute myocardial infarction.
      Therefore, we evaluated the prognostic significance of proximal versus distal
      coronary artery occlusion in patients with acute myocardial infarction that was
      treated with primary PCI. Between 1994 and 2001, patients with a first acute
      myocardial infarction that was treated with primary PCI were analyzed. A lesion
      was considered proximal if it was located proximal to the first diagonal branch
      in the left anterior descending coronary artery (LAD), the first marginal obtuse
      branch in the left circumflex coronary artery, and the first right acute marginal
      branch in the right coronary artery. Lesions distal of these side branches were
      considered distal. In total, 1,468 patients were analyzed. Left ventricular
      ejection fraction (LVEF) for proximal LAD lesions was lower than that for distal
      ones (37 +/- 11% vs 42 +/- 11%, p <0.0001). Adjusted relative risk of 3-year
      mortality for proximal versus distal LAD was 4.04 (95% confidence interval 1.95
      to 8.38). In patients with infarcts related to the right or left circumflex
      coronary artery, no significant association between lesion location and LVEF or
      mortality was seen. No difference was seen in adjusted 3-year mortality between
      distal LAD and non-LAD-related infarcts (p = 0.145). In conclusion, our analysis
      shows that, even in patients with acute myocardial infarction that is treated
      with primary PCI, infarcts related to the proximal LAD have the worst 3-year
      survival and lowest residual LVEF compared with distal LAD or non-LAD-related
      infarcts.

PMID- 16616015
TI  - Should primary percutaneous coronary intervention be the preferred method of
      reperfusion therapy for patients with renal failure and ST-elevation acute
      myocardial infarction?
AB  - Data from patients who had ST-elevation acute myocardial infarction and renal
      failure and were enrolled in the 2002 Acute Coronary Syndrome Israeli Survey
      (ACSIS) were studied to determine the effect of different myocardial reperfusion
      modalities on short- and long-term outcomes. Thirty-day crude mortalities were
      8.3% in the thrombolysis group, 40.0% in the primary percutaneous coronary
      intervention group, and 29.7% in the no-reperfusion group (p = 0.03). Crude and
      adjusted mortality odds ratios that were observed at 7, 30, and 365 days, with
      the thrombolysis group as the reference, were 3.1 to 8.1 in the percutaneous
      coronary intervention group and 1.5 to 4.6 in the no-reperfusion group. Our
      results suggest that thrombolysis may represent the preferred modality of
      reperfusion therapy in patients with renal failure and ST-elevation acute
      myocardial infarction. A large randomized prospective study is needed to confirm
      these results.

PMID- 16616016
TI  - Relation of B-type natriuretic peptide early after acute myocardial infarction to
      left ventricular diastolic function and extent of myocardial damage determined by
      magnetic resonance imaging.
AB  - Early after acute myocardial infarction, the relation between plasma B-type
      natriuretic peptide (BNP) and extent of myocardial scar formation and diastolic
      dysfunction remains unclear. In 32 consecutive patients early (5 +/- 3 days)
      after a first acute myocardial infarction, delayed contrast-enhanced magnetic
      resonance (MR) imaging was performed to define myocardial scar. Diastolic
      function was assessed using phase-contrast MR measurements of mitral flow and
      septal tissue velocities (tissue MR imaging) to estimate left ventricular (LV)
      filling pressures. MR study was immediately followed by BNP measurement. BNP
      related to LV ejection fraction (r = -0.52, p = 0.002), extent of myocardial scar
      (percent delayed hyperenhancement of LV mass, r = 0.49, p = 0.005; transmural
      index, r = 0.58, p <0.001), and estimated LV filling pressures (ratio of early
      diastolic mitral flow velocity to early diastolic mitral annular velocity, r =
      0.51, p = 0.003). In multivariate analysis, transmural index and early diastolic
      mitral flow velocity/early diastolic mitral annular velocity were independent
      predictors of BNP levels (p <0.05, power of 0.99 at alpha = 0.05). In conclusion,
      among patients with recent myocardial infarction, high BNP levels are
      independently associated with extent of myocardial scar tissue and estimated LV
      filling pressures.

PMID- 16616017
TI  - N-terminal pro-brain natriuretic peptide on admission in patients with acute
      myocardial infarction and correlation with scintigraphic infarct size, efficacy
      of reperfusion, and prognosis.
AB  - We investigated whether N-terminal pro-brain natriuretic peptide (NT-pro-BNP)
      that was measured on admission in patients with acute myocardial infarction (AMI)
      predicts the efficacy of reperfusion or whether NT-pro-BNP provides prognostic
      information independent of infarct size as estimated by single-photon emission
      computed tomographic scintigraphy. The study included 174 patients with ST
      segment elevation AMI who were admitted within 24 hours of pain onset. NT-pro-BNP
      level was measured on admission. Paired scintigraphic studies (before and 7 to 14
      days after reperfusion) were performed to assess infarct size and define
      myocardial salvage. One-year clinical follow-up was assessed. Patients were
      categorized into the high NT-pro-BNP group (57 patients in the upper tertile of
      NT-pro-BNP) and low NT-pro-BNP group (117 patients in the middle and lower
      tertiles of NT-pro-BNP). Initial median perfusion defect was 35.0% (interquartile
      rage 20.0 to 53.0%) of the left ventricle in the high NT-pro-BNP group versus
      19.0% (interquartile range 10.0 to 32.2) of the left ventricle in the low NT-pro
      BNP group (p <0.001). Median salvage index was 0.36 (interquartile range 0.16 to
      0.86) in the high NT-pro-BNP group versus 0.53 (interquartile range 0.31 to 0.75)
      in the low NT-pro-BNP group (p = 0.22). After adjustment in Cox's proportional
      hazards model, NT-pro-BNP remained an independent correlate of 1-year mortality
      (adjusted hazard ratio 2.31, 95% confidence interval 1.09 to 4.89, p = 0.03, high
      vs low NT-pro-BNP group). In conclusion, NT-pro-BNP measured on admission in
      patients with AMI correlates with scintigraphic area at risk and predicts
      prognosis but does not predict the efficacy of mechanical reperfusion by stenting
      or angioplasty.

PMID- 16616018
TI  - Effect of pre-myocardial infarction angina pectoris on post-myocardial infarction
      arrhythmias after reperfusion therapy.
AB  - It has not been concluded whether there is a relation between pre-myocardial
      infarction angina pectoris (pre-MIAP) and reperfusion arrhythmia, although pre
      MIAP has been reported to have a beneficial effect in preserving left ventricular
      function. Moreover, factors that are associated with reperfusion arrhythmias in
      patients with acute myocardial infarction (AMI) who have been successfully
      reperfused by reperfusion therapy are unknown. This study examined the predictive
      factors of reperfusion arrhythmias in patients with AMI who underwent successful
      reperfusion. The Japanese Intervention Trial in Myocardial Infarction study is a
      prospective, randomized trial that compares the outcome in patients with AMI who
      undergo intracoronary thrombolysis or primary percutaneous conventional coronary
      balloon angioplasty. One hundred ten consecutive patients with AMI who had been
      successfully reperfused in this study were categorized into 2 groups according to
      whether or not patients showed reperfusion arrhythmias. Multivariate logistic
      regression analysis was performed using 11 clinical factors to clarify the
      determinants of reperfusion arrhythmia. Reperfusion arrhythmias developed in 65
      of 110 patients (59%). Multivariate logistic regression analysis confirmed that
      inferior AMI and pre-MIAP were independently associated with reperfusion
      arrhythmia. The odds ratio that predicted reperfusion arrhythmias was 2.37 (p =
      0.0056) for inferior AMI. In contrast, the odds ratio was minimal at 0.24 for pre
      MIAP (p = 0.036). In conclusion, pre-MIAP suppresses reperfusion arrhythmias, and
      inferior AMI is an independent factor for reperfusion arrhythmias.

PMID- 16616019
TI  - Prognostic value of nocturnal melatonin levels as a novel marker in patients with
      ST-segment elevation myocardial infarction.
AB  - We evaluated the possible relation between circulating levels of nocturnal
      melatonin, C-reactive protein, and the development of adverse cardiovascular
      events in patients with ST-segment elevation myocardial infarction. Patients who
      had developed adverse events during follow-up had significantly lower nocturnal
      melatonin levels than patients without events.

PMID- 16616020
TI  - Effects of early statin treatment on symptomatic heart failure and ischemic
      events after acute myocardial infarction in Japanese.
AB  - Statins have been shown to prevent coronary artery disease and to preserve left
      ventricular function in dilated cardiomyopathy. We hypothesized that early use of
      statins would decrease cardiovascular events, including heart failure in patients
      with acute myocardial infarction (AMI). To examine the effect of statins in
      Japanese patients with AMI, a prospective, randomized, open-label trial was
      conducted in 486 patients with normal total cholesterol levels. Patients were
      randomly assigned to receive any available statin (n = 241) within 96 hours of
      AMI onset or no statin (n = 245) and were followed for up to 24 months. The
      primary end point was a composite of cardiovascular death, nonfatal AMI,
      recurrent symptomatic myocardial ischemia, congestive heart failure, and stroke.
      Event rate for the primary end point was lower in the statin group than in the
      nonstatin group (6.1% vs 11.4%, p = 0.0433). The statin group had a lower risk of
      congestive heart failure and symptomatic myocardial ischemia (p = 0.0154 and
      0.0264, respectively). In conclusion, early lipid-lowering therapy with statins
      decreases recurrent cardiovascular events, in particular, congestive heart
      failure.

PMID- 16616021
TI  - Assessment of coronary arterial plaque by optical coherence tomography.
AB  - The purpose of this study was to analyze the ability of optical coherence
      tomography (OCT) to identify coronary arterial plaque diagnosed by histologic
      examination. We examined 166 sections from 108 coronary arterial segments of 40
      consecutive human cadavers (24 men and 16 women; mean age 74 +/- 7 years). The
      plaque type was classified as fibrous (n = 43), fibrocalcific (n = 82), or lipid
      rich (n = 41). The accuracy of OCT and intravascular ultrasound (IVUS) in
      characterizing the plaque type was studied, with the histologic consensus
      diagnosis serving as the gold standard. OCT, as well as IVUS, had high
      sensitivity and specificity for characterizing the different types of
      atherosclerotic plaque. OCT had a higher sensitivity for characterizing lipid
      rich plaques than IVUS (85% vs 59%, p = 0.03). In conclusion, the high resolution
      of OCT permitted evaluation of lipid-rich plaques more accurately than IVUS.

PMID- 16616022
TI  - Electrocardiographic findings and incident coronary heart disease among
      participants in the Atherosclerosis Risk in Communities (ARIC) study.
AB  - The associations of many electrocardiographic (ECG) abnormalities at rest with
      incident coronary heart disease (CHD) are not completely established, and whether
      individual ECG abnormalities convey similar risk across gender and race is
      uncertain. We studied the independent association of several ECG findings with
      incident CHD, testing for effect modification by gender and race, in a large,
      population-based, prospective cohort study. Findings from the baseline 12-lead
      electrocardiograms in 1987 to 1989 were classified according to the Minnesota
      Code in 12,987 black and white men and women, aged 45 to 64 years, who were
      initially free of CHD and the use of specific cardiac medications. The incidence
      of CHD was ascertained through 2000. After adjustment for multiple cardiovascular
      risk factors, the ECG findings that had the highest hazard rate ratios (HRRs) for
      incident CHD, when considered singly, were left ventricular hypertrophy with ST-T
      strain pattern in white men (HRR 6.50) and in black women (HRR 2.31) and, in the
      whole cohort, major (HRR 2.27) and minor (HRR 2.47) ST depression and major T
      wave abnormalities (HRR 2.12). Statistically significant associations were also
      found in the whole cohort for minor Q waves and left ventricular hypertrophy by
      the Cornell definition, but not for a prolonged QTc interval, major ventricular
      conduction defects, or ST elevation. In conclusion, several 12-lead ECG findings
      were independently associated with incident CHD in middle-aged adults. With only
      a few exceptions, the associations were similar for blacks and whites.

PMID- 16616023
TI  - Comparison of sirolimus versus paclitaxel eluting stents for treatment of
      coronary in-stent restenosis.
AB  - In patients with in-stent restenosis (ISR) inside bare metal stents, drug-eluting
      stents reduce the recurrence of restenosis compared with balloon angioplasty.
      However, few data are available about this therapeutic modality in the case of
      diffuse restenosis. The aim of this study was to evaluate the immediate and mid
      term outcome of sirolimus- and paclitaxel-eluting stent implantation in diffuse
      ISR and determine the predictors of clinical and angiographic restenosis
      recurrence. A series of 161 consecutive patients with 194 diffuse ISR lesions
      (>10 mm) treated with drug-eluting stent implantation were evaluated. Major
      adverse cardiac events were defined as death, myocardial infarction, and the need
      for target lesion revascularization. During a mean follow-up of 8.2 +/- 3.4
      months, the cumulative incidence of major adverse cardiac events was 19% in the
      SES group and 24% in the PES group (p = 0.56). Angiographic follow-up was
      performed in 80% of the lesions. The overall restenosis rate was 22% and was not
      significantly different between lesions treated with sirolimus-eluting (20%) or
      paclitaxel-eluting (25%, p = 0.55) stents. The incidence of restenosis was higher
      in diabetics (32%) than in nondiabetics (16%, odds ratio 2.5, 95% confidence
      interval 1.1 to 5.5, p = 0.02). By multivariate analysis, diabetes was confirmed
      to be the only independent predictor of recurrent restenosis (odds ratio 3.53,
      95% confidence interval 1.39 to 9.02, p = 0.008). In conclusion, drug-eluting
      stent implantation for diffuse ISR is associated with acceptable clinical and
      angiographic results. The association of diffuse restenosis and diabetes mellitus
      is an unfavorable condition leading to a high risk of recurrence.

PMID- 16616024
TI  - Comparison of cardiovascular risk of noncardiac surgery following coronary
      angioplasty with versus without stenting.
AB  - Previous studies have shown a high incidence of cardiovascular complications when
      noncardiac surgery (NCS) is performed after coronary stenting. No study has
      compared the outcomes of NCS after stenting compared with percutaneous
      transluminal coronary angioplasty (PTCA) alone. The records of all patients who
      underwent NCS within 3 months of percutaneous coronary intervention at our
      institution were reviewed for adverse clinical events with the end points of
      acute myocardial infarction, major bleeding, and death < or = 6 months after NCS.
      A total of 216 consecutive patients were included in the study. Of these, 122
      (56%) underwent PTCA and 94 (44%) underwent stenting. A total of 26 patients
      (12%) died, 13 in the stent group (14%) and 13 in the PTCA group (11%), a
      nonsignificant difference. The incidence of acute myocardial infarction and major
      bleeding was 7% and 16% in the stent group and 6% and 13% in the PTCA group (p =
      NS), respectively. Significantly more events occurred in the 2 groups when NCS
      was performed within 2 weeks of percutaneous coronary intervention. In
      conclusion, our study has demonstrated high rates of perioperative morbidity and
      mortality after NCS in patients undergoing PTCA alone, as well as stenting. These
      findings support the current guidelines regarding the risk of NCS after stenting
      but suggest they be extended to PTCA as well.

PMID- 16616025
TI  - Usefulness and safety of percutaneous coronary interventions for cardiac
      transplant vasculopathy.
AB  - Late morbidity and death as a result of progressive coronary vascular
      obliteration remains a major unsolved problem after orthotopic heart
      transplantation. Various percutaneous catheter intervention (PCI) methods have
      been used to treat transplant coronary artery disease (CAD), but few reports have
      assessed the longitudinal results of these procedures. Of 1,440 cardiac
      transplant patients at University of California, Los Angeles, Medical Center,
      treated between 1984 and 2004, 65 patients who had undergone orthotopic heart
      transplantation underwent PCI on a total of 156 coronary artery lesions because
      of transplant CAD between July 1993 and August 2004. The procedural success rate
      was 93%. Angiographic follow-up was available for 42 patients and 101 lesions 9.5
      +/- 5.8 months after PCI. The global restenosis rate was 36%. Multivariate
      analysis was used to assess 49 clinical, angiographic, and immunologic variables
      per lesion. The use of a cutting balloon increased the risk of restenosis (odds
      ratio 11.5, p <0.01) and the use of stents decreased the risk of restenosis (odds
      ratio 0.34, p <0.05) compared with other PCI methods. The restenosis rate with
      drug-eluting stents was 19%, lower than that with bare metal stents (31%). Of the
      65 patients, 20 (31%) died within 1.9 +/- 1.8 years after PCI. The actuarial
      survival rate was 56% at 5 years after the first PCI. In conclusion, although the
      restenosis rate after PCI was higher than that in nontransplant patients with
      CAD, the immediate and long-term results were acceptable in this high-risk
      population. Despite the intense inflammation associated with transplant CAD, drug
      eluting stents appeared to reduce the occurrence of restenosis. Compared with
      historical controls, PCI may also improve the actuarial survival rate of patients
      undergoing orthotopic heart transplantation.

PMID- 16616026
TI  - Effects of colesevelam hydrochloride on low-density lipoprotein cholesterol and
      high-sensitivity C-reactive protein when added to statins in patients with
      hypercholesterolemia.
AB  - Elevated high-sensitivity C-reactive protein (hs-CRP) levels are associated with
      an increased risk of atherosclerotic coronary heart disease (CHD). The addition
      of the bile acid sequestrants, such as colesevelam hydrochloride (HCl), to
      statins further reduces low-density lipoprotein (LDL) cholesterol levels.
      However, the effects of approved cholesterol-lowering bile acid sequestrants on
      hs-CRP have not previously been reported. Three randomized, double-blind, placebo
      controlled, parallel, 6-week clinical trials of similar design investigated the
      efficacy of adding colesevelam HCl to stable simvastatin, atorvastatin, or
      pravastatin treatment in 204 patients with primary hypercholesterolemia. The
      primary end point was the mean percent change in the LDL cholesterol levels.
      Secondary end points included the effects on other lipid parameters and hs-CRP
      levels. A pooled analysis showed that adding colesevelam HCl to statin therapy
      significantly lowered LDL cholesterol levels (21 mg/dl or 16% mean reduction from
      baseline, p = 0.0013, and 11 mg/dl or 9% mean reduction compared with placebo, p
      = 0.0003). Four times as many patients receiving colesevelam HCl plus a statin
      achieved a LDL cholesterol target of <100 mg/dl compared with patients receiving
      a statin plus placebo (39% vs 10%, respectively, p <0.0001). The incidence of
      mild gastrointestinal adverse effects was slightly higher in the colesevelam HCl
      plus statin group than in the placebo plus statin group. Finally, the differences
      in the change in hs-CRP levels with colesevelam HCl plus statin therapy were
      significant compared with the changes with placebo plus statin (median change 
      23%, p = 0.0069). In conclusion, this is the first report suggesting that an
      approved cholesterol-lowering bile acid sequestrant, specifically colesevelam
      HCl, decreases hs-CRP levels when added to statin therapy.

PMID- 16616027
TI  - Recurrence rates of arrhythmias during pregnancy in women with previous
      tachyarrhythmia and impact on fetal and neonatal outcomes.
AB  - In women with heart disease, sustained arrhythmias can result in an increased
      risk to the mother and fetus. The purpose of this study was to determine the
      recurrence rates of arrhythmias during pregnancy in women with cardiac rhythm
      disorders and examine the impact on fetal and neonatal outcomes. Women with
      tachyarrhythmias before pregnancy who underwent obstetric care at the Toronto
      General and Mount Sinai Hospitals from 1990 to 2002 were included. The recurrence
      rates of arrhythmias were calculated. A multivariate logistic model was used to
      identify predictors of fetal complications. Seventy-three women had 87
      pregnancies; 36 pregnancies were in women with a history of paroxysmal
      supraventricular tachycardia, 23 with paroxysmal atrial fibrillation or atrial
      flutter (AF/Afl), 6 with persistent AF/Afl, and 22 with ventricular tachycardia.
      In the women in sinus rhythm at baseline, 44% (36 of 81 pregnancies) developed
      recurrences of tachyarrhythmias during pregnancy or in the early postpartum
      period. The specific recurrence rates during pregnancy in women with a history of
      supraventricular tachycardia, paroxysmal AF/Afl, and ventricular tachycardia were
      50%, 52%, and 27%, respectively. The 6 women in AF/Afl at baseline remained in
      this rhythm throughout their pregnancy. Adverse fetal events occurred in 17 of
      the 87 pregnancies (20%). Adverse fetal events occurred more commonly in women
      who developed antepartum arrhythmias (RR 3.4, 95% confidence interval 1.0 to
      11.0, p = 0.045) compared with those who did not. In conclusion, in women with
      preexisting cardiac rhythm disorders, exacerbation of arrhythmia during pregnancy
      is common. Recurrence of arrhythmia during the antepartum period increases the
      risk of adverse fetal complications, independent of other maternal and fetal risk
      factors.

PMID- 16616028
TI  - Atrial and ventricular volume and function evaluated by magnetic resonance
      imaging in patients with persistent atrial fibrillation before and after
      cardioversion.
AB  - Atrial fibrillation (AF) is the most common cardiac arrhythmia and 25% of those
      >40 years old will experience AF. Left atrial size and left ventricular function
      are independently related to cardiovascular morbidity and mortality. Our aim was
      to evaluate cardiac volume and function using magnetic resonance imaging in
      patients with persistent AF and to describe the changes after cardioversion (CV).
      Sixty consecutive patients with persistent AF and 19 healthy volunteers had
      cardiac volumes evaluated by cinematographic breath-hold magnetic resonance
      imaging. Patients with AF were evaluated before CV and at 1, 30, and 180 days
      after CV, if still in sinus rhythm. All atrial and ventricular volumes and left
      ventricular mass decreased and ejection fractions increased significantly after
      CV (p <0.0001 for all variables). Atrial and ventricular diastolic volumes
      increased significantly the day after CV. The atrial diastolic volumes had
      decreased significantly at 30 days and ventricular volumes at 180 days. The
      atrial systolic volumes decreased significantly the day after CV, but the
      ventricular systolic volumes remained constant the day after CV and decreased
      thereafter. Only the right atrial volumes were normalized 180 days after CV. The
      same results were found in a subgroup of patients with lone AF. In conclusion,
      reversal of atrial dimensions and function happened earlier than ventricular
      reversal after CV in persistent AF. Atrial reversal began immediately and
      ventricular reversal was not seen before 30 days after CV. Our results suggest
      that the changes to the left atrium and both ventricles caused by AF could be
      permanent and that CV of AF may be preferable.

PMID- 16616029
TI  - Effect of radiofrequency catheter ablation for atrial fibrillation on left atrial
      cavity size.
AB  - Left atrial (LA) remodeling is associated with atrial fibrillation (AF).
      Radiofrequency catheter ablation offers a good treatment option for AF, with
      reasonable long-term results. The purpose of the present study was to assess
      whether LA reverse remodeling occurs after successful catheter ablation. Fifty
      seven consecutive patients (45 men; age 53 +/- 8 years) with symptomatic drug
      refractory AF were treated with radiofrequency catheter ablation. The patients
      were divided into 2 groups on the basis of AF recurrence as determined by Holter
      monitoring and 12-lead electrocardiographic findings at 6 weeks and 3 months of
      follow-up (sinus rhythm [SR] group, no recurrence; AF group, AF recurrence). At
      baseline and 3 months of follow-up, 2-dimensional echocardiography was performed
      to assess LA size and dimensions. Furthermore, LA volumes were measured at end
      systole and end-diastole. After 3 months, 39 of 57 patients (68%) maintained SR.
      At 3 months of follow-up, the LA anteroposterior diameter showed a significant
      reduction in the SR group (4.5+/- 0.3 vs 4.2 +/- 0.2 cm, p <0.01), and an
      additional increase was observed in the AF group (4.5+/- 0.3 vs 4.8 +/- 0.3 cm, p
      <0.05). Furthermore, the LA end-systolic and end-diastolic volumes decreased
      significantly in the SR group from baseline to follow-up (59 +/- 12 vs 50 +/- 11
      ml, p <0.01, and 37 +/- 9 vs 31 +/- 7 ml, p <0.01, respectively). However, a
      tendency toward an increase in LA volumes was observed in the AF group. In
      conclusion, the results of this study have demonstrated that LA reverse
      remodeling occurs after successful radiofrequency catheter ablation for AF.

PMID- 16616030
TI  - Ventricular remodeling during long-term right ventricular pacing following His
      bundle ablation.
AB  - To investigate ventricular remodeling during long-term right ventricular (RV)
      pacing after His bundle ablation (HBA) in patients with atrial arrhythmias, a
      retrospective analysis was performed on echocardiographic data from 45 patients
      (mean age 57 +/- 11 years) with atrial arrhythmias who underwent HBA and
      pacemaker implantation (HBA-PI) to control ventricular rate. Echocardiography was
      performed 1 year before HBA-PI, and up to 7 +/- 2 years of follow-up was
      conducted. An inverse linear relation was found between the relative increase of
      left ventricular (LV) end-diastolic diameter (EDD) during long-term RV pacing and
      LVEDD before HBA-PI (r = -0.61, p<0.001). Patients were divided into 2 groups:
      those with LVEDDs smaller than the mean LVEDD of 50 mm (group I, 46 +/- 2 mm, n =
      28) and those with LVEDDs >50 mm (group II, 56 +/- 4 mm, n = 17). Before HBA-PI,
      patients in group I had significantly smaller LV weights (167 +/- 44 vs 238 +/-
      56 g) and LV end-systolic diameters (30 +/- 2 vs 42 +/- 7 mm) and higher LV
      ejection fractions (64 +/- 5% vs 49+/- 12%) than those in group II. In group I,
      long-term RV pacing increased LVEDD, LV end-systolic diameter, LV weight, and
      left atrial diameter; increased mitral regurgitation; and decreased the LV
      ejection fraction and LV fractional shortening. No significant changes were
      observed during long-term RV pacing in group II. In conclusion, long-term RV
      pacing after HBA adversely affects LV structure and function in patients with
      initially normal LV dimensions and function.

PMID- 16616031
TI  - Comparison of morbidity in women versus men with heart failure and preserved
      ejection fraction.
AB  - Patients with heart failure (HF) and preserved ejection fraction (HF-PEF)
      constitute up to 30% to 50% of patients with HF, and HF-PEF affects women more
      often than men. Not much is known about the role of gender in the clinical
      presentation, symptoms, or disease severity of HF-PEF or about the contribution
      of these differences to gender differences in morbidity and mortality in patients
      with HF-PEF. This study examined gender differences in clinical presentation,
      hospitalization, and mortality in patients with HF-PEF (ejection fraction > or =
      50%) enrolled in the ancillary arm of the Digitalis Investigation Group trial.
      Time-to-event analysis was performed using Cox proportional-hazards modeling. The
      study cohort included 719 patients (378 men, 341 women). At baseline, compared
      with men, women were older and had greater clinical severity of HF, as evidenced
      by worse New York Heart Association functional class, more frequent symptoms and
      signs of HF, and more treatment with diuretics. Ischemia was identified as the
      primary cause of HF in 46% of women and 56% of men (p = 0.01). During a median
      follow-up of 39 months, crude mortality was similar in women and men (24.6% and
      24.3%, p = 0.93), but more women were hospitalized for HF (26.7% vs 15.9%, p
      <0.001). After adjustment for baseline differences, female gender was an
      independent predictor of lower mortality (hazard ratio 0.59, 95% confidence
      interval 0.43 to 0.82), but HF hospitalization rates were similar between men and
      women (hazard ratio 1.09, 95% confidence interval 0.77 to 1.53). In conclusion,
      although the clinical manifestations of HF appear to be more severe in women with
      HF-PEF, after adjustment for baseline clinical differences, HF hospitalizations
      are not increased and survival expectancy is better for women compared with men.

PMID- 16616032
TI  - Usefulness of magnetic resonance imaging for the diagnosis of right ventricular
      dysplasia in children.
AB  - Cardiac magnetic resonance (CMR) has been helpful in adults in the diagnosis of
      arrhythmogenic right ventricular dysplasia. Short of direct surgical observation
      or autopsy, no gold standard exists. CMR diagnostic criteria include right atrial
      and ventricular dilation, regional right ventricular (RV) wall motion
      abnormalities, outflow tract ectasia, and myocardial fatty infiltration. To
      determine whether adult diagnostic criteria are useful in children referred for
      CMR for this diagnosis, the images and records of 81 patients (aged 11.5 +/- 5.5
      years) over an 8-year period were reviewed. Histories included ventricular
      tachycardia, palpitations, dilated right ventricle, syncope, near sudden death,
      or family history of RV dysplasia. Four families were studied with parents who
      had RV dysplasia diagnosed by surgery, explanted heart, or CMR. CMR imaging
      included T1-weighted imaging, cine, 1-dimensional RV myocardial tagging, and
      phase-encoded velocity mapping, and 2 patients underwent delayed-enhancement CMR.
      Only 1 of the 81 patients met 5 of the criteria. None of the others met >2 of the
      criteria, and only 2 patients met 1 or 2 criteria. For questionable regional wall
      motion abnormalities, RV myocardial tagging was helpful. In conclusion, CMR of
      patients with a history suspicious for the diagnosis of RV dysplasia is a low
      yield test in children. This may be due to the evolving nature of the disease,
      which does not manifest itself from a morphologic or ventricular-function
      standpoint until later in development. Follow-up studies as patients age may be
      advantageous.

PMID- 16616033
TI  - Incidence and risk distribution of heart failure in adolescents and adults with
      congenital heart disease after cardiac surgery.
AB  - Heart failure (HF) is a major problem in the long-term follow-up of adults with
      congenital heart disease (CHD) after cardiac surgery. The purpose of this study
      was to evaluate risk factors for HF in patients with CHD. N-terminal-pro-brain
      natriuretic peptide and maximal oxygen uptake (VO2max) were measured in 345
      consecutive patients with CHD. HF was defined as an elevated N-terminal-pro-brain
      natriuretic peptide level (> or = 100 pg/ml) and reduced VO2max (< or = 25
      ml/kg/min). The HF criteria were met by 89 patients. These patients were
      significantly older (mean +/- SEM 30.8 +/- 0.9 vs 24.8 +/- 0.5 years), had
      significantly lower maximal heart rates (149 +/- 3 vs 164 +/- 1 beats/min), and
      had larger end-diastolic right ventricular diameters (36 +/- 1 vs 27 +/- 1 mm)
      and right ventricular pressure estimated by Doppler flow velocities of tricuspid
      valve regurgitation (2.9 +/- 0.1 vs 2.3 +/- 0.03 m/s). Mean fractional shortening
      of the left ventricle was within the normal range. To estimate risk
      stratification, odds ratios for HF were determined for the most frequently
      occurring types of congenital heart defects and surgical procedures. In
      conclusion, HF in adults with CHD predominately depends on diagnosis, age, the
      frequency of reoperation, and right ventricular function and may be related to
      chronotropic incompetence indicated by lower maximal heart rates.

PMID- 16616034
TI  - Effect of acute cocaine administration on the QTc interval of habitual users.
AB  - The proarrhythmic effects of cocaine may be mediated in part by its effects on
      cardiac repolarization properties. This study evaluated the acute effects of
      smoking cocaine 25 mg on the electrocardiograms of 14 habitual cocaine users
      during a 12-minute observation period. After cocaine administration, heart rate
      increased by a mean of 22 beats/min (p <0.0001). One patient developed
      accelerated junctional rhythm, and 5 had nonspecific ST-T-wave abnormalities. The
      electrocardiograms revealed significant prolongation of the QTc interval (p
      <0.001) after cocaine administration. In addition, T-wave amplitude decreased and
      U-wave amplitude increased in response to cocaine use (p <0.05). QRS duration was
      unchanged by cocaine, whereas the PR interval shortened slightly. The
      repolarization changes observed after cocaine use were similar to those reported
      for other sympathomimetic agents and may be a contributing factor in the
      association between cocaine use and ventricular arrhythmias.

PMID- 16616035
TI  - Safety of exercise stress testing in patients with abnormal concentrations of
      serum potassium.
AB  - The objective of this study was to determine the safety of performing exercise
      stress testing in patients with abnormal serum potassium concentrations. Data
      were reviewed from 9,084 patients (mean age 63 +/- 12 years) referred for
      exercise echocardiography who had serum potassium measured <48 hours before the
      test were reviewed, and the occurrence of arrhythmias during stress testing was
      determined. Of 10,272 studies, 9,067 (88%) were in patients with normokalemia and
      1,205 (12%) were in patients with abnormal serum potassium concentrations: 309
      (26%) with hypokalemia (mean 3.4 +/- 0.16 mmol/L) and 896 (74%) with hyperkalemia
      (mean 5.1 +/- 0.19 mmol/L). Ventricular and supraventricular ectopy were common
      during exercise. Only 1 patient (potassium 4.9 mmol/L) had sustained ventricular
      tachycardia; all other episodes were nonsustained. Although ventricular and
      supraventricular ectopy are common during exercise testing, life-threatening
      arrhythmias are not. Exercise testing is generally safe despite mild to moderate
      hypokalemia or hyperkalemia.

PMID- 16616036
TI  - Relation of plasma insulin levels to forearm flow-mediated dilatation in healthy
      volunteers.
AB  - Although several observations suggest that insulin resistance/compensatory
      hyperinsulinemia (IR/CH) has a direct effect on endothelial function,
      independently of the metabolic abnormalities associated with the defect in
      insulin action, this relation has not been evaluated in apparently healthy
      individuals. To address this issue, we measured endothelial-dependent
      vasodilation in response to forearm ischemia (flow-mediated dilation [FMD]) in 47
      nonsmoking, healthy volunteers without known risk factors for atherosclerosis.
      Measurements were also made of multiple anthropometric, metabolic, and
      hemodynamic variables related to IR/CH. Decreases in FMD were significantly
      correlated (analysis of variance for linear trend) with (1) male gender (p =
      0.003), (2) waist circumference (p = 0.038), (3) higher fasting plasma insulin (p
      = 0.015) and triglyceride concentrations (p = 0.023), and (4) lower
      concentrations of high-density lipoprotein cholesterol (p = 0.001). Multivariate
      linear regression analysis indicated that only plasma insulin (beta -0.424) was
      independently associated (p <0.001) with changes in FMD, and individual
      differences in insulin concentrations, along with gender and brachial artery
      diameter at baseline, accounted for approximately 39% of the variability in FMD.
      In conclusion, IR/CH is an independent predictor of decreases in endothelial
      dependent vasodilation in apparently healthy individuals, in the absence of
      traditional risk factors for atherosclerosis.

PMID- 16616037
TI  - Frequency and causes of implantable cardioverter-defibrillator therapies: is
      device therapy proarrhythmic?
AB  - Implantable cardioverter-defibrillator (ICD) shocks diminish patients' quality of
      life, increase health care resource utilization, and may lead to other adverse
      sequelae. Better understanding of the factors that lead to ICD therapies, and
      better strategies to avoid unnecessary therapies, are needed to optimize patient
      outcomes. Data from major randomized clinical trials involving the use of ICDs
      and cardiac resynchronization therapy-defibrillator devices were reviewed to
      determine control group mortality rates, control group sudden death rates, and
      the frequency of appropriate and inappropriate ICD therapies. In all studies that
      classified deaths, appropriate ICD therapies outnumbered control group sudden
      cardiac deaths by a factor of 2 to 3. Some of these episodes can be explained by
      device programming, by the treatment of potentially unsustained tachycardias, and
      by errors of episode classification. Another underexplored possibility is that
      device therapy is proarrhythmic. Reasons for frequent therapies and methods to
      prevent them are discussed, as well as the notion of device proarrhythmia and the
      potentially detrimental effects of ICD shocks. These issues clearly affect the
      overall benefit of device therapy and have important implications for patient
      management and health care delivery.

PMID- 16616038
TI  - Cardiovascular disease risk factors and cognitive impairment.
AB  - The role of cardiovascular disease risk factors in the occurrence and progression
      of cognitive impairment has been the subject of a significant number of
      publications but has not achieved widespread recognition among many physicians
      and educated laymen. It is apparent that the active treatment of certain of these
      cardiovascular disease risk factors is accompanied by a reduced risk for
      cognitive impairment. Patients with hypertension who are treated experience fewer
      cardiovascular disease events as well as less cognitive impairment than similar
      untreated patients. Patients who exercise may present with less cognitive
      impairment, and obesity may increase the risk for cognitive impairment. Lipid
      abnormalities and genetic markers are associated with an increased risk for
      cardiovascular disease and cognitive impairment. Autopsy studies have
      demonstrated a correlation between elevated levels of cholesterol and amyloid
      deposition in the brain. Research has demonstrated a relation between
      atherosclerotic obstruction lesions in the circle of Willis and dementia.
      Diabetes mellitus is associated with an increased risk for cardiovascular disease
      and cognitive impairment. A number of nonpharmacologic factors have a role in
      reducing the risk for cognitive impairment. Antioxidants, fatty acids, and
      micronutrients may have a role, and diets rich in fruits and vegetables and other
      dietary approaches may improve the outlook for patients considered at risk for
      cognitive impairment.

PMID- 16616039
TI  - Statins may prevent postoperative atrial fibrillation through autonomic
      modulation.

PMID- 16616041
TI  - Etiology of acute myeloid leukemia in the elderly.
AB  - The biologic and epidemiologic study of acute myeloid leukaemia (AML) in the
      elderly is in its infancy. Most epidemiologic data attempting to ascertain the
      etiology of AML have been obtained from younger cohorts or patients with therapy
      related AML. The increasing prevalence of deletional and complex karyotypes in
      elderly AML patients implies a cumulative genotoxicity over time for this
      subgroup, given the similar spectrum of abnormalities following exposure to known
      genotoxic agents such as alkylating chemotherapeutic drugs. Exposure to benzene,
      radiation, and tobacco smoke are clear but weak risk factors for AML. Polymorphic
      variants in several genes responsible for genomic protection and integrity are
      now also weak risk factors for AML. Future epidemiologic studies should correlate
      exposure data with well-defined biologic subtypes of AML.

PMID- 16616042
TI  - General approach to, and perspectives on clinical research in, older patients
      with newly diagnosed acute myeloid leukemia.
AB  - Most patients aged>or=55 to 60 years who are treated for newly diagnosed acute
      myeloid leukemia (AML) receive a combination of an anthracycline plus cytarabine
      (ara-C). A principal thesis of this chapter is that such therapy is
      unsatisfactory for the great majority of such patients. In particular, the
      >or=15% risk of death in the month following the start of treatment is difficult
      to justify given median survivals of less than 1 year in the patients who do not
      die early. Thus, investigational therapy should be recommended for most, if not
      all, older patients. In patients for whom such therapy is not feasible, low-dose
      ara-C is a reasonable alternative except for patients with de novo disease and a
      normal karyotype, who might benefit more from an anthracycline+ara-C combination,
      and patients with either a poor performance status, abnormal organ function, or
      age>or=80, for whom supportive/palliative care only is recommended. Distinctions
      are made between investigational therapies likely associated with lower and
      higher risks of treatment-related mortality (TRM). The former are preferable
      initial treatment in patients aged 70 and above, or with abnormal cytogenetics.
      Three topics are discussed that are likely to be relevant to future clinical
      research in older patients: the possibility of delaying therapy to gain
      information about prognosis with initial induction therapy, the clinical value of
      responses less than conventional complete remission (CR), and the possibility of
      looking for larger differences between treatments in randomized clinical trials.

PMID- 16616043
TI  - Treatment of older patients with acute myeloid leukemia--new agents.
AB  - The experience of most collaborative study groups is that the outcome for older
      patients has, unlike in younger patients, failed to improve over the last two
      decades. In addition there are a substantial number of older patients who do not
      enter collaborative group trials because they are not considered suitable for an
      intensive chemotherapy approach. During this era many combinations of
      chemotherapeutic agents at different dose levels have been tried. It is clear
      that novel agents and new approaches must be used to improve the situation, and
      should include options for patients who are not fit for intensive treatment.
      Fortunately, the increased understanding of the molecular basis and heterogeneity
      of the disease has fostered the development of novel agents. Chemo-resistance is
      a key characteristic of acute myeloid leukaemia (AML) in older patients and a
      number of randomized trials have now been completed to assess this approach. New
      possibilities of selectively killing leukemic cells and/or modifying toxicity are
      in prospect with the development of antibody directed chemotherapy in the form of
      gemtuzumab ozogamicin (Mylotarg; Wyeth, Philadelphia, PA). New drugs such as
      clofarabine or cloretazine are being evaluated. Molecular mechanisms, whether
      recognized or not, have been targeted by the use of FLT-3 and farnesyl
      transferase (FT) inhibitors. With several new agents to evaluate, novel
      approaches to trial design aimed at detecting options likely to make a useful
      impact are needed.

PMID- 16616044
TI  - Allogeneic transplantation for the elderly patient with acute myelogenous
      leukemia or myelodysplastic syndrome.
AB  - Acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) are diseases
      of the elderly. Allogeneic hematopoietic stem cell transplantation (HSCT) offers
      the possibility of cure for these malignancies, but until recently its use was
      restricted to younger patients due to prohibitive treatment-related mortality.
      Improvements in supportive care and development of reduced-intensity preparative
      regimens have allowed patients in the sixth, seventh, and to a lesser extent,
      eighth decade of life to be treated with allogeneic transplantation. Major
      obstacles to extending this form of treatment to older patients are lack of
      promptly available donors, graft-versus-host disease (GVHD), delayed immune
      recovery, and the high prevalence of refractory and relapsed disease intrinsic to
      the natural history of these myeloid malignancies. Here we review current results
      of allogeneic blood and marrow transplantation for AML and MDS in the elderly.

PMID- 16616045
TI  - Immunologic approaches to acute leukemia in the elderly.
AB  - The outcome of older patients with acute leukemia remains poor with few long-term
      survivors, indicating the need for treatment approaches that target pro-apoptotic
      pathways not influenced by chemotherapy resistance. For a long time, natural
      killer (NK) cells have held promise for cancer immunotherapy because, unlike T
      lymphocytes, they can kill tumor cells without the need for tumor-specific
      antigen recognition. In the treatment of acute leukemia, NK cell-based therapies
      have focused on in vivo expansion and activation with cytokines with only modest
      success. However, recent understanding of the importance of NK receptors for the
      recognition and lysis of leukemia cells suggests novel therapeutic strategies.
      The balance of inhibitory and activating signals through surface receptors,
      recognizing major histocompatibility complex (MHC) class I and class I-like
      molecules on target cells, determines whether NK cells activate killing. In this
      review, we discuss the biologic rationale for therapeutic strategies harnessing
      NK cells and focus on novel directions for their future use in elderly patients
      with acute leukemia.

PMID- 16616046
TI  - Management of acute lymphoblastic leukemia in older patients.
AB  - Although the median age for adults with acute lymphoblastic leukemia (ALL) is
      older than 60 years, relatively few of these patients have been enrolled on
      prospective clinical trials. The presence of coexisting medical disorders and
      unfavorable cytogenetic and biologic disease characteristics within this
      population presents considerable challenges for successful treatment using
      conventional chemotherapy programs. Selected patients have achieved remission and
      long-term survival following intensive chemotherapy. Philadelphia (Ph) chromosome
      (BCR/ABL)-positive ALL is particularly common among older patients. The
      availability of specific tyrosine kinase inhibitors is changing the prognosis for
      this challenging subset.

PMID- 16616047
TI  - Approach to the complications of treatment for acute leukemia in the elderly.
AB  - Acute leukemia is common in the elderly and, due to the aging population and
      poorer prognosis, represents a major challenge. Elderly acute leukemia patients
      have been arbitrarily defined as >or=55 to 65 years of age and are
      underrepresented in clinical trials. There are physiologic differences between
      elderly and non-elderly patients. A comprehensive understanding of these
      differences allows the development of a systematic approach to assessing the
      risks for treatment-related complications. Use of a comprehensive geriatric
      assessment (CGA), initially developed and validated in the general geriatric
      population, may allow more accurate assessment of the likelihood of chemotherapy
      induced complications and allow for proactive risk minimization. Once
      complications to therapy develop, aggressive treatment is essential. Treatment
      related to common complications that arise from therapy will be reviewed. Further
      research directed at this population is required.

PMID- 16616048
TI  - Probability effects in the stop-signal paradigm: the insula and the significance
      of failed inhibition.
AB  - In the present randomized, mixed-trial event-related fMRI study, we examined the
      neural mechanisms underlying inhibitory control using a stop-signal paradigm in
      which stop-signal frequency was manipulated parametrically across blocks. As
      hypothesized, presenting stop signals less frequently was accompanied by a
      stronger set to respond to the go stimuli as subjects were faster in responding
      to go stimuli on no stop-signal trials and made more commission errors (i.e.,
      were less successful in inhibiting the go response) on stop-signal trials. When
      response inhibition was successful, having to inhibit responses more frequently
      compared to less frequently was associated with greater activation in occipital
      areas. This presumably reflects enhanced visual attention to the stop signal.
      When response inhibition failed, greater activity was observed in bilateral
      insula when stop signals were presented less compared to more frequently. The
      insula may thus play a role in processing the significance of inhibitory failure.

PMID- 16616049
TI  - The short chain sugar acid, 2-buten-4-olide, activates oxytocin-secreting neurons
      but not arginine vasopressin-secreting neurons in the hypothalamus of rats.
AB  - The effects of intraperitoneal (i.p.) administration of 2-buten-4-olide (2-B4O),
      an endogenous sugar acid, on the hypothalamo-neurohypophyseal system were
      examined in rats. Plasma oxytocin (OXT) levels were significantly increased 15-60
      min after i.p. administration of 2-B4O (100 mg/kg), whereas plasma arginine
      vasopressin (AVP) did not change. Dual immunostaining revealed that Fos-like
      immunoreactivity (LI) was predominantly observed in OXT-secreting neurons in the
      paraventricular (PVN) and the supraoptic nuclei (SON) 120 min after i.p.
      administration of 2-B4O. In addition, many Fos-LI neurons were observed in the
      nucleus of the tractus solitarius (NTS) after i.p. administration of 2-B4O. These
      results suggest that a peripherally administered high dose of 2-B4O activates OXT
      secreting neurons in the hypothalamus through activation of NTS neurons, possibly
      as a result of a stress response.

PMID- 16616050
TI  - Development of the corticospinal tract in the mouse spinal cord: a quantitative
      ultrastructural analysis.
AB  - The growth of corticospinal tract (CST) axons was studied quantitatively at the
      7th cervical (C7) and the 4th lumbar (L4) spinal segments in the balb/cByJ mice
      at the ages of postnatal day (P) 0, 2, 4, 6, 8, 10, 14, and 28. The cross
      sectional area of the CST increased progressively with time. Unmyelinated axons,
      the most prominent CST element during early development, reached maximum at C7
      and L4 on P14. Two phases of increase in the number of unmyelinated axons were
      observed at C7, while only one surge of axonal outgrowth was found at the L4
      level. Pro-myelinated axons, defined as axons surrounded by only one layer of
      oligodendrocytic process, were first seen at P2 and P4 in the C7 and the L4
      level, respectively, followed by a dramatic increase in the number of myelinated
      axons from P14 onwards at both spinal levels. Myelination of the CST axons
      occurred topographically in a dorsal-to-ventral pattern. The number of growth
      cones increased rapidly at the C7 level to reach its maximum at P4, while those
      at L4 increased steadily to the peak at P10. Growth cones with synapse-like
      junctions were occasionally observed in the growing CST. Degenerating axons and
      growth cones partly accounted for the massive axon loss at both spinal segments
      during CST development. Overall, the mouse CST elements changed dynamically in
      numbers during postnatal development, suggesting a vigorous growing and pruning
      activity in the tract. The mouse CST also showed a similar growth pattern to that
      of the rat CST.

PMID- 16616051
TI  - Adrenomedullin 2 protects rat cerebral endothelial cells from oxidative damage in
      vitro.
AB  - Adrenomedullin 2 (AM2, intermedin) is a recently identified new member of the
      calcitonin gene-related peptide family. We examined whether AM2 can attenuate the
      increased blood-brain barrier permeability and cerebral endothelial cell (CEC)
      death induced by oxidative stress in vitro. Hydrogen peroxide (H(2)O(2), 0.5 mM)
      induced a continuous decrease of the transendothelial electrical resistance
      (TEER) and resulted in intercellular gap formations in rat CECs co-cultured with
      astrocytes. AM2 induced cAMP and nitric oxide production, increased TEER,
      enhanced peripheral localization of F-actin bands, and attenuated the increased
      permeability induced by H(2)O(2). AM2 treatment preserved mitochondrial membrane
      potential and improved CEC viability in H(2)O(2) treated cultures. These effects
      of AM2 were similar to those what were reported for adrenomedullin. These results
      suggest that AM2 protects CECs against oxidative injury in vitro.

PMID- 16616052
TI  - Neuroprotective effects of neuregulin-1 in rat models of focal cerebral ischemia.
AB  - The purpose of this study was to investigate the therapeutic efficacy and
      mechanism of recombinant human NRG-1 to attenuate ischemia/reperfusion brain
      injury. NRG-1(3.0 ng/kg) was applied intravascularly 10 min before middle
      cerebral artery occlusion (MCAO) and then focal cerebral ischemia for 90 min and
      reperfusion for 24 h. The rats were scored post-reperfusion for neurological
      deficits and infarct volume in the brain was assessed by 2,3,5
      triphenyltetrazolium chloride(TTC). Apoptosis was evaluated by TUNEL staining.
      Reverse transcription polymerase chain reaction (RT-PCR) was used to measure
      changes of caspase-3 mRNA. The level of TNF-alpha was determined using enzyme
      linked immunosorbent assay (ELISA). Our results demonstrated that recombinant
      human NRG-1 could reduce cerebral infarct volume by about 71% (P < 0.05) and
      TUNEL positive cells when given immediately before MCAO, and improved behavior of
      animals. Furthermore, we also showed that NRG-1 could also decrease the
      expression of caspase-3 mRNA and production of TNF-alpha protein. These data
      suggest that pre-administration of NRG-1 attenuates cerebral ischemia and
      reperfusion injury. This protective effect may be involved in the inhibition of
      caspase-3 and TNF-alpha.

PMID- 16616053
TI  - Modulation of cortically induced rhythmical jaw movements by stimulation of the
      red nucleus in the rat.
AB  - We study whether stimulation of the red nucleus (RN) can modulate rhythmical jaw
      movements in rats anesthetized by urethane. Rhythmical jaw movements were induced
      by repetitive electrical stimulation of the two cortical masticatory areas (area
      A: the orofacial motor cortex; area P: the insular cortex). Stimuli applied to
      the RN did influence rhythmical jaw movements induced by stimulation of the A
      area. Stimuli applied in the jaw-closing phase increased the amplitude of the jaw
      closing movement. Stimuli applied in the jaw-opening phase disturbed the rhythm
      of jaw movements and induced a small jaw-closing movement. Stimuli applied to the
      RN did not influence rhythmical jaw movements induced by stimulation of the P
      area. These results indicate that the RN is involved in the modulation of
      rhythmical jaw movements induced by stimulation of the A-area.

PMID- 16616054
TI  - Insulin resistance, abnormal energy metabolism and increased ischemic damage in
      the chronically infarcted rat heart.
AB  - OBJECTIVE: Many patients with heart failure have whole-body insulin resistance
      and reduced cardiac fluorodeoxyglucose uptake, but whether these metabolic
      changes have detrimental effects on the heart is unknown. Here, we tested whether
      there is a link between insulin resistance and ischemic damage in the chronically
      infarcted Wistar rat heart, postulating that the heart would have decreased
      insulin sensitivity, with lower GLUT4 glucose transporter protein levels due to
      high circulating free fatty acid (FFA) concentrations. A decreased capacity for
      glucose uptake would lower glycolytic adenosine triphosphate (ATP) production and
      thereby increase ischemic injury in the infarcted heart. METHODS AND RESULTS: In
      vivo left ventricular ejection fractions, measured using echocardiography, were
      40% lower in rats 10 weeks after coronary artery ligation than in sham-operated
      control rats. Insulin-stimulated D[2-3H]glucose uptake was 42% lower in isolated,
      perfused, infarcted hearts. Myocardial GLUT4 glucose transporter protein levels
      were 28% lower in the infarcted hearts and correlated negatively with ejection
      fractions and with fasting plasma FFA concentrations. Compared with controls,
      chronically infarcted hearts had 46% lower total glucose uptake and three-fold
      faster ATP hydrolysis rates, measured using phosphorus-31 nuclear magnetic
      resonance spectroscopy, during 32-min ischemia at 0.4 ml/min/gww. During
      reperfusion, recovery of left ventricular developed pressure in infarcted hearts
      was 42% lower than in control hearts. CONCLUSIONS: Glucose uptake, in response to
      insulin or ischemia, was lower in the chronically infarcted rat heart and
      associated with increased circulating FFA concentrations and decreased GLUT4
      levels. Thus, infarcted hearts had greater ATP depletion, and consequently
      incurred greater damage, during ischemia.

PMID- 16616056
TI  - Endothelial nitric oxide synthase G894T gene polymorphism in Chilean subjects
      with coronary artery disease and controls.
AB  - BACKGROUND: Nitric oxide (NO) from the endothelium, produced by oxidation of l
      arginine to L-citruline for the action at the endothelial nitric oxide synthase
      (eNOS), is considered an important atheroprotective factor. The Glu298Asp (G894T)
      polymorphic variant of the eNOS gene has been implicated in the development of
      coronary artery disease (CAD). We investigated the association between occurrence
      of CAD documented by angiography and the G894T polymorphism of the NOS3 gene in
      Chilean individuals. METHODS: A total of 112 unrelated patients with diagnosis of
      CAD and 72 controls were included in this study. G894T gene polymorphism was
      analyzed by polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP). RESULTS: The frequency of TT homozygous genotype for G894T
      polymorphism was 7% in CAD patients and 1% in the control group. However, the
      genotype distribution and allele frequencies were not significantly different
      between CAD and control subjects (P>0.05). Moreover, the odds ratio for CAD
      associated with the T variant failed to reach statistical significance (OR=1.5;
      95% CI: 0.87-2.59, P>0.05). CONCLUSION: These findings suggest that the G894T
      polymorphism of the eNOS gene was not associated with CAD in Chilean individuals.

PMID- 16616055
TI  - Defective CD3zeta chain expression in Herpesvirus saimiri (HVS)-derived T-cell
      lines in gastric adenocarcinoma.
AB  - Low expression of the CD3zeta chain has been reported in patients with cancer and
      it has been suggested that tumor-derived factors are involved in its
      downregulation. The expression of CD3zeta chain was measured in T-cell lines from
      patients with gastric adenocarcinoma and healthy volunteers and grown in vitro
      for several months and, hence, in the absence of any tumor-derived factors. T
      cell lines of mucosal origin were obtained by Herpesvirus saimiri transformation
      from gastric cancer patients. The expression of CD3zeta and CD3epsilon was
      measured by flow cytometry and Western-blot analysis. Calcium mobilization and
      apoptosis rate were also measured. The levels of CD3zeta, but not CD3epsilon,
      chain on the cell surface were significantly reduced in T-cell lines derived from
      patients with gastric cancer when cultured in the absence of IL-2. Western-blot
      analysis of total cell extracts or lipid raft fractions confirmed this finding.
      Calcium mobilization, a measure of signal transduction, was reduced in T cell
      lines from patients with gastric cancer. We conclude that T cells from patients
      with cancer express lower levels of CD3zeta. This downregulation is not caused by
      a direct effect of tumor-derived factors but, rather, it appears to be inherent
      to the patient cells. The low CD3zeta expression would render T lymphocytes
      unable to control the growth of tumor cells.

PMID- 16616057
TI  - A rapid and sensitive assay for the quantitation of carboxypeptidase N, an
      important regulator of inflammation.
AB  - BACKGROUND: Carboxypeptidase N is a plasma zinc metallocarboxypeptidase which is
      constitutively expressed in the liver and was identified as the enzyme
      responsible for inactivating bradykinin and kallidin by removing the C-terminal
      arginine. Because CPN can cleave the C-terminal arginine of C3a, C4a and C5a it
      is often referred to as anaphylatoxin inactivator. Markedly reduced levels of
      circulating CPN are associated with recurrent angioedema and abnormal cutaneous
      polymorphonuclear cell infiltration. METHODS: In this paper we describe a fast
      kinetic coupled enzymatic assay for the sensitive measurement of carboxypeptidase
      N activities in serum samples. The assay makes use of the excellent CPN substrate
      Benzoyl-L-Alanyl-L-Arginine. RESULTS: This novel assay is very fast, easy to
      perform and combines good reliability and reproducibility with excellent
      correlation with the HPLC-assisted assay (r=0.927; n=140). CONCLUSION: The
      presented assay can be used for high throughput screening of this important
      regulator of inflammation in clinical plasma or serum samples.

PMID- 16616058
TI  - Preanalytical pitfalls of blood sampling to measure true circulating matrix
      metalloproteinase 9 and tissue inhibitors of matrix metalloproteinases.

PMID- 16616059
TI  - Detection of telomerase activity by the TRAP assay and its variants and
      alternatives.
AB  - Telomerase activity is closely connected to problems of cellular immortality,
      proliferative capacity, differentiation, cancer and aging. Correspondingly,
      techniques for its detection have been essential for progress in telomere biology
      and are of still increasing importance in molecular diagnostics and therapy of
      cancer. This article reviews the development of the telomere repeat amplification
      protocol (TRAP) and its various modifications as the most widespread assay to
      detect and measure telomerase activity. Alternative possibilities of telomerase
      activity detection are also discussed which make it possible to omit the PCR
      mediated amplification of telomerase products. These approaches are based on
      recent advances in highly sensitive detection systems.

PMID- 16616061
TI  - The origin of B-cell chronic lymphocytic leukemia.
AB  - An immunobiologic approach has led to substantial changes in our current view of
      chronic lymphocytic leukemia (CLL). Several questions remain unsolved and the
      definition of the cell origin of CLL is still prominent. The presence of somatic
      mutations of IGHV genes indicates that, at least in a portion of cases, CLL cells
      had encountered an antigen during the natural history of the disease. Unmutated
      (UM) cases show a remarkable skewing in IGHV gene usage. In addition, all CLL
      cases, both mutated (M) and UM, show a common surface phenotype which is
      significantly activated and similar to the surface phenotype of antigen (Ag)
      experienced B cells. The properties of CLL B-cell receptors (BCR) resemble those
      observed in normal B cells upon Ag interaction, and gene profiling analyses
      revealed that both subsets share striking similarities with the so-called memory
      B cells. The detailed analyses of the complementary determining region 3 (CDR3)
      sequences of the leukemic immunoglobulin (Ig) receptors showed that unrelated
      patients in different parts of the world express very similar if not identical
      BCR. Remarkably, similar V(H)DJ(H) rearrangements have been identified in both UM
      and M-CLL, suggesting an antigenic selection in both subsets of the disease.
      From all this evidence, the concept has arisen that the cell of origin,
      regardless its mutational status, has to be "an Ag-experienced" B cell that gives
      rise to a malignant clone that appears to be more dynamic than previously
      appreciated and whose progression is favored by a number of molecular and
      cellular interactions that occur in tissues.

PMID- 16616062
TI  - Epigenetics in chronic lymphocytic leukemia.
AB  - Enormous evidence has accumulated in the past decades that establishes the
      importance of epigenetic modifications in cancer and has resulted in shifting the
      focus from entirely genetic-based studies to integrated studies involving both
      genetic and epigenetic alterations. Chronic lymphocytic leukemia (CLL) is one
      such example where studies involving epigenetic aberrations have accelerated the
      search for affected genes, which was initially restricted to commonly deleted
      chromosomal regions. Many novel genes that are epigenetically silenced in CLL
      have been identified. Advances in the understanding of post-translational histone
      modifications and DNA methylation in normal and in CLL cells have proven to be
      extremely beneficial in finding powerful diagnostic markers, as well as in
      exploring novel therapies. At present, the field of epigenetics is at an evolving
      stage, but there is no doubt that further unraveling of its cause and effects in
      transformed cells will bring a new revolution in cancer therapeutics.

PMID- 16616063
TI  - Genomics of chronic lymphocytic leukemia microRNAs as new players with clinical
      significance.
AB  - Chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in the
      Western world, is characterized by predominantly nondividing malignant CD5+ B
      cells overexpressing the anti-apoptotic Bcl2 protein. Significant familial
      aggregation with largely unknown mode of inheritance has been demonstrated. Until
      recently little else was known regarding the events leading to CLL initiation and
      progression. New findings support the view that CLL is a genetic disease where
      the main alterations occur at the level of transcriptional/post-transcriptional
      regulation of the malignant cells genome because of deregulations of a new class
      of genes named microRNAs (miRNAs). miRNA genes miR-15a and miR-16-1, located at
      13q14.3, are frequently deleted and/or downregulated in patients with B-cell CLL.
      Both microRNAs negatively regulate Bcl2 at a post-transcriptional level and this
      repression is enough to induce apoptosis. Therefore, miR-15 and miR-16 are
      natural antisense Bcl2 interactors that could be used for therapy of Bcl2
      overexpressing tumors. Furthermore, microRNA expression profiles can distinguish
      normal B cells from malignant B cells in CLL. A unique microRNA signature is
      associated with prognostic factors such as mutations in the immunoglobulin heavy
      chain variable-region gene (IgV(H)) or high expression of the 70-kd zeta
      associated protein (ZAP-70+) and disease progression in CLL. Mutations in miRNA
      transcripts are frequent, some of them germ-line, and may have functional
      importance and may predispose to CLL and to a spectrum of associated
      malignancies.

PMID- 16616064
TI  - The clinical and biologic importance of neovascularization and angiogenic
      signaling pathways in chronic lymphocytic leukemia.
AB  - Angiogenesis has been found to be an important regulator in the growth and
      metastasis of solid tumors. More recent studies have also demonstrated the
      importance of this biologic process in normal hematopoietic cell development and
      the pathophysiology of several hematologic malignancies. This review provides an
      overview of the clinical and biologic importance of angiogenesis in chronic
      lymphocytic leukemia (CLL). Patients with CLL have detectable levels of both
      plasma and cellular pro- and anti-angiogenic cytokines, as well as abnormal
      neovascularization in the marrow and lymph nodes. Recent evidence suggests a
      vascular endothelial growth factor (VEGF)-based autocrine pathway promotes the
      survival of CLL B cells in part through upregulation of anti-apoptotic proteins.
      Additionally, interactions between CLL B cells and their microenvironment
      generate alterations in the secretion of angiogenic factors that result in
      enhanced leukemic B-cell resistance to apoptotic cell death. From a clinical
      standpoint, interpatient variation is observed in markers of angiogenesis and
      appears to have prognostic implications. Several clinical trials evaluating the
      efficacy of anti-angiogenic agents for treatment of patients with CLL are
      underway with promising preliminary results. Additional research is needed to
      identify the regulation of aberrant and critical angiogenic pathways in CLL B
      cells, to determine how angiogenic markers can be used to improve prognostication
      for CLL patients, and to explore how the angiogenic characteristics of CLL B
      cells can best be manipulated for therapeutic benefit.

PMID- 16616065
TI  - Risk stratification in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) follows an extremely variable clinical course
      with survival ranging from months to decades. Available treatments can often
      induce remissions, but eventually all patients relapse. Recently, there has been
      major progress in the identification of molecular and cellular markers that may
      predict the tendency for disease progression in patients with CLL. Genomic
      aberrations, the mutational profile of IgVH genes and its surrogate marker ZAP-70
      expression, and serum markers like B2-microglobulin (beta2-MG) and thymidine
      kinase (TK) provide prognostic information for individual patients independently
      of clinical disease characteristics. These molecular markers are about to enter
      the stage of risk stratification for individual patients in clinical trials.

PMID- 16616066
TI  - Familial chronic lymphocytic leukemia.
AB  - The role of inherited genetic factors in the etiology of chronic lymphocytic
      leukemia (CLL) and other B-cell lymphoproliferative disorders (LPDs) is now well
      established. Significant familial aggregation of CLL and B-cell LPDs has been
      demonstrated, but the mode of inheritance is unknown. Identifying genes that when
      mutated confer an increased risk of these diseases is of immediate clinical
      relevance in terms of primary and secondary interventions. Furthermore, their
      identification provides for a greater understanding of the mechanisms of B-cell
      tumorigenesis in general. Here we review the current status of knowledge relating
      to inherited susceptibility to CLL and the strategies that are being employed to
      identify disease-causing mutations.

PMID- 16616067
TI  - Initial therapy for patients with chronic lymphocytic leukemia.
AB  - Evolution of frontline treatment for patients with chronic lymphocytic leukemia
      (CLL) has been driven by the objective of increasing complete remission (CR)
      rates and achieving maximum elimination of leukemia. As a result, effective
      combination regimens incorporating new agents such as monoclonal antibodies have
      been developed. Beyond morphologic CR, evaluation for residual disease by
      multicolor flow cytometry or molecular techniques may provide a tool to assess
      potentially more effective therapies. Although new prognostic factors correlate
      with time to treatment and survival have been identified, the utility of these
      factors in predicting response rates or response duration has not been
      established. Clearly, strides have been made in developing effective treatments
      that are improving remission duration with the ultimate goal of improving
      survival for patients with CLL. Herein, we review the recent progress in
      frontline therapies for patients with CLL.

PMID- 16616068
TI  - Treatment of relapsed chronic lymphocytic leukemia: old and new therapies.
AB  - There are several initial therapies available for chronic lymphocytic leukemia
      (CLL) that offer extended disease-free or treatment-free survival time. However,
      once patients relapse, particularly after fludarabine-based therapy, treatment
      choices have remained limited. Newer therapies have now become available,
      including alemtuzumab, fludarabine-based combinations, rituximab,
      methylprednisolone, alternative nucleoside analogs, flavopirodol, lenalidomide,
      signal transduction inhibitors/small molecules, and new monoclonal antibodies. We
      discuss selection of therapy for the relapsed patient using risk stratification
      and the role of clinical research in continuing to pursue therapeutic advances
      against CLL.

PMID- 16616069
TI  - Vaccine- and immune-based therapy in chronic lymphocytic leukemia.
AB  - B-cell chronic lymphocytic leukemia (CLL) would appear to be an ideal target of T
      cell-mediated responses against the cancer cell. The cancer arises in cells that
      can act as antigen-presenting cells (APCs), CLL cells express tumor antigens, and
      the cells can be a target of the allogeneic T cells in a graft-versus-leukemia
      effect. Despite these potential benefits, immune responses against CLL cells have
      been difficult to elicit. CLL induces immune defects in the host, the tumor cells
      are inefficient APCs, and therapies given to patients with CLL are themselves
      immunosuppressive. Successful vaccination approaches in this disease will require
      steps to overcome these difficulties, including steps to improve the immune
      defects in this disease, identification of the targets of the immune response to
      monitor immunologic responses, and improved presentation of antigen.

PMID- 16616070
TI  - Autoimmune complications of chronic lymphocytic leukemia.
AB  - Autoimmune complications are common in chronic lymphocytic leukemia (CLL),
      occurring in up to a quarter of all patients during the course of the illness. By
      far the most common manifestation is autoimmune hemolytic anemia (AIHA), followed
      by immune thrombocytopenia (ITP). It is not true to say that autoimmunity is
      confined to the formed elements of the blood since conditions such as
      paraneoplastic pemphigus and acquired angioedema do occur in CLL, but
      nonhematologic autoimmunity is very rare indeed. The pathogenesis of autoimmunity
      in CLL is unknown. It may be related to the ability of the CLL cells to act as
      antigen-presenting cells (APCs), and to process antigen (particularly the Rh
      protein) so as to reveal cryptic peptides that are seen as foreign by helper T
      cells. It is likely that a failure of regulatory T-cell function is also
      involved. Autoimmune episodes may be triggered by treatment, particularly with
      purine analogues. Such episodes are often severe and may be fatal. Treatment of
      CLL-associated autoimmunity follows conventional protocols, but non-response to
      primary treatments is not uncommon. Promising results have been obtained with
      cyclosporine and rituximab.

PMID- 16616071
TI  - Infectious complications of chronic lymphocytic leukemia.
AB  - Infectious complications continue to be one of the major causes of morbidity and
      mortality in patients with chronic lymphocytic leukemia (CLL). The pathogenesis
      of infections in these patients is multifactorial. Hypogammaglobulinemia is an
      important predisposing factor for infection in patients with early-stage disease
      and for those treated with conventional alkylating agents. However, the
      proportion of patients treated with purine analogs and monoclonal antibodies such
      as rituximab and alemtuzumab is increasing. As a result of this therapy, these
      patients often experience profound and sustained T-cell immunodeficiency.
      Consequently, the spectrum of organisms causing infections in these patients is
      changing from common bacterial organisms to less common opportunistic pathogens
      such as Pneumocystis, Listeria, mycobacteria, herpesviruses, and Candida. This
      review focuses on the pathogenesis and risk factors for infections in patients
      with CLL, the spectrum of infectious organisms associated with the newer agents,
      and the management of these infections with an emphasis on prophylaxis and
      vaccination strategies.

PMID- 16616072
TI  - Richter's transformation in chronic lymphocytic leukemia.
AB  - Richter's syndrome (RS) is characterized by the development of high-grade non
      Hodgkin's lymphoma (NHL) in a patient with chronic lymphocytic leukemia (CLL) or
      small lymphocytic lymphoma. At The University of Texas M.D. Anderson Cancer
      Center the incidence of RS is 3.9%. The large cells of RS may arise through
      transformation of the original CLL clone or represent a new neoplasm. RS may be
      triggered by viral infections, such as Epstein-Barr virus (EBV). Trisomy 12 and
      chromosome 11 abnormalities, as well as multiple genetic defects, have been
      described in patients with RS. These abnormalities may cause CLL cells to
      proliferate and, by facilitating the acquisition of new genetic abnormalities, to
      transform into RS cells. The therapeutic strategies for RS typically include
      therapies developed for NHL or acute lymphoblastic leukemia. The reported
      response rates with these therapies are 5% to 43%, and the median survival
      duration ranges from 5 to 8 months. The median overall survival duration at our
      institution of patients with RS is 9.1 months (95% confidence interval, 7.8 to 11
      months), and the median failure-free survival duration is 7.1 months (95%
      confidence interval, 5.1 to 10.4 months). Patients appear to benefit from
      cytoreductive therapy consisting of chemotherapy and immunotherapy, followed by
      allogeneic stem cell transplantation, as postremission therapy. As part of a
      program aiming to cure RS, we are currently conducting a clinical trial of
      oxaliplatin, fludarabine, and cytarabine in combination with rituximab and
      recommend postremission therapy, including allogeneic stem cell transplantation
      in patients with available donors.

PMID- 16616073
TI  - Prolymphocytic leukemias.
AB  - T and B subtypes of prolymphocytic leukemias (PLLs) are rare, highly aggressive
      lymphoid malignancies with characteristic morphologic, immunophenotypical,
      cytogenetic, and molecular features. Recent studies have highlighted the role of
      specific oncogenes such as TCL1, MTCP-1, and ATM in the case of T-cell and p53
      mutations in the case of B-cell PLLs. Despite the advances in the understanding
      of the biology of these conditions, prognosis for these patients remains poor
      with short survival and no curative treatment. The advent of monoclonal antibody
      therapy has improved treatment options for this group. In particular, the use of
      Campath-1H, in T-PLL has more than doubled median survival. The role of
      allogeneic transplant with nonmyeloablative conditioning needs to be explored
      further.

PMID- 16616074
TI  - Differential effects of age-of-acquisition for concrete nouns and action verbs:
      evidence for partly distinct representations?
AB  - There is growing evidence that words that are acquired early in life are
      processed faster and more accurately than words acquired later, even by adults.
      As neuropsychological and neuroimaging studies have implicated different brain
      networks in the processing of action verbs and concrete nouns, the present study
      was aimed at contrasting reaction times to early and later-acquired action verbs
      and concrete nouns, in order to determine whether effects of word learning age
      express differently for the two types of words. Our results show that while word
      frequency affected both types of words in the same way, distinct learning age
      effects were observed for action verbs and concrete nouns. A further experiment
      specified that this difference was observed for verbs describing actions
      belonging to the human motor repertoire, but not for verbs denoting actions past
      this repertoire (e.g., to neigh). We interpret these data within a recently
      emerging framework according to which language processing is associated with
      sensory motor programs.

PMID- 16616075
TI  - Representing object colour in language comprehension.
AB  - Embodied theories of cognition hold that mentally representing something red
      engages the neural subsystems that respond to environmental perception of that
      colour. This paper examines whether implicit perceptual information on object
      colour is represented during sentence comprehension even though doing so does not
      necessarily facilitate task performance. After reading a sentence that implied a
      particular colour for a given object, participants were presented with a picture
      of the object that either matched or mismatched the implied colour. When asked if
      the pictured object was mentioned in the preceding sentence, people's responses
      were faster when the colours mismatched than when they matched, suggesting that
      object colour is represented differently to other object properties such as shape
      and orientation. A distinction between stable and unstable embodied
      representations is proposed to allow embodied theories to account for these
      findings.

PMID- 16616076
TI  - Why stereotypes don't even make good defaults.
AB  - Many concepts have stereotypes. This leaves open the question of whether concepts
      are stereotypes. It has been argued elsewhere that theories that identify
      concepts with their stereotypes or with stereotypical properties of their
      instances (e.g., Rosch, E. (1978). Principles of categorization. In E. Rosch & B.
      B. Lloyd (Ed.), Cognition and Categorization. Hillsdale, NJ: Lawrence Erlbaum
      Associates; Smith, E. E., Medin, D. L. (1981). Categories and Concepts.
      Cambridge, MA: Harvard University Press.) fail to provide an adequate account of
      the compositionality of concepts (Fodor, J., Lepore, E. (1996). The red herring
      and the pet fish: Why concepts still cannot be prototypes. Cognition, 58, 253
      270.; Fodor, J. (1998). Concepts: Where cognitive science went wrong. New York,
      NY: Oxford University Press.). This paper extends this argument and reports an
      experiment suggesting that participants do not assume, even as a default
      strategy, that complex concepts inherit the stereotypes of their constituents.
      Thus propositions such as "Baby ducks have webbed feet" were judged to be less
      likely to be true than propositions like "Ducks have webbed feet." Moreover,
      manipulation of the type and number of noun phrase modifiers revealed a
      systematic departure from the unmodified noun's stereotype both with the addition
      of stereotypical modifiers ("Quacking ducks have webbed feet" versus "Ducks have
      webbed feet") and with the addition of a second modifier ("Baby Peruvian ducks
      have webbed feet" versus "Baby ducks have webbed feet"). Thus, in the general
      case the stereotypical properties of a head noun are systematically discounted
      when that head noun combines with modifiers. This effect represents a general
      principle of conceptual combination that argues against the inheritance of
      stereotypical features of concepts as a default strategy. Instead, we advocate a
      model of conceptual combination where concepts remain inert under combination,
      supported by a separate machinery that introduces pragmatic and knowledge
      dependent inferences.

PMID- 16616077
TI  - Permeability of ovine primordial follicles to different cryoprotectants.
AB  - OBJECTIVE: To determine the behavior of isolated primordial follicles that were
      exposed to different concentrations of dimethyl sulfoxide (DMSO), ethylene glycol
      (EG), propylene glycol (PROH), and glycerol (GLY). DESIGN: Isolated primordial
      follicles were exposed to the cryoprotectant (CPA) solution and photographed to
      calculate their volume at different periods of exposure. SETTING: Laboratorio
      Renzo Giuliani, University of Florence, Italy. ANIMAL(S): Lambs, 30-40 days old.
      INTERVENTION(S): Isolation of primordial follicles and subsequent exposure to
      CPA. MAIN OUTCOME MEASURE(S): Follicular volume. RESULT(S): At 2 minutes of CPA
      exposure, all follicles appeared to be shrunken. At approximately 5 minutes,
      shrinkage ceased, and follicles started to swell, absorbing the CPA and water to
      maintain osmotic equilibrium. When DMSO was tested, follicular dehydration in all
      concentrations did not exceed 17%; with PROH and EG, it reached 33% and 27%,
      respectively. The highest degree of dehydration (48%) was seen with GLY. In
      almost all tested concentrations, follicular shrinkage occurred up to 5 minutes.
      CONCLUSION(S): Volume changes in isolated primordial follicles can fluctuate
      according to the CPA used and its concentration.

PMID- 16616078
TI  - Analysis of apoptotic cell death, Bcl-2, and p53 protein expression in freshly
      fixed and cryopreserved ovarian tissue after exposure to warm ischemia.
AB  - OBJECTIVE: To evaluate the effect of ischemia time on the expression of Bcl-2 and
      p53 proteins on freshly fixed and cryopreserved-thawed ovarian tissue. DESIGN:
      Experimental study using porcine animal model. SETTING: Biological Resources
      Unit, Cleveland Clinic Foundation. ANIMAL(S): Eight nonpregnant adult sows.
      INTERVENTION(S): Bilateral oophorectomy was performed in eight sows and the
      ovaries were subjected to time-dependent (1, 10, 20, and 30 min) warm ischemia
      (room temperature). Each specimen was divided into two parts, One was fixed as a
      fresh tissue (freshly fixed) and the other was subjected to cryopreservation,
      thawing, and fixation (cryopreserved). MAIN OUTCOME MEASURE(S): Apoptosis (TUNEL
      assay) and Bcl-2 and p53 protein expression (immunoperoxidase method) were
      assessed. RESULT(S): At 1, 10, 20, 30 min of warm ischemia the apoptotic indices
      were: 1) statistically significantly higher in the atretic (1.36 +/- 0.20, 1.59
      +/- 0.20, 1.67 +/- 0.22, and 1.67 +/- 0.24, respectively) than in the nonatretic
      follicles (0.69 +/- 0.06, 0.69 +/- 0.06, 0.76 +/-, and 0.06, 0.71 +/- 0.06,
      respectively; P<.05); 2) not significantly different between freshly fixed and
      cryopreserved tissues; and 3) nonsignificantly higher with the increased duration
      of ischemia. Bcl-2 expression was seen in the granulosa but not in the theca
      cells of most of the healthy and occasional atretic follicles. p53 expression was
      seen only in few atretic follicles. Increased duration of ischemia was associated
      with insignificant incremental rise of the number of follicles with Bcl-2
      expression (1.82 +/- 0.30, 2.01 +/- 0.44, 2.02 +/- and 0.35, 2.05 +/- 0.42 for
      healthy follicles at 1, 10, 20, and 30 min, respectively; P=.99). CONCLUSION(S):
      (1) Apoptosis is involved in follicular atresia; (2) Bcl-2 is induced by warm
      ischemia; and (3) cryopreservation insult does not alter the apoptotic signals
      with short tissue preparation time.

PMID- 16616079
TI  - Immunohistochemical analysis of collagen expression in human corpora lutea during
      the menstrual cycle and early pregnancy.
AB  - OBJECTIVE: To investigate the characteristic structure and function of human
      corpora lutea (CL), various types of collagen expression were determined in the
      CL tissues during the menstrual cycle and early pregnancy. DESIGN: In vitro
      experiment. SETTING: Department of obstetrics and gynecology at a medical
      university. PATIENT(S): Regulatory cycling women and pregnant women with ovarian
      tumor and ectopic pregnancy who underwent adnexectomy. INTERVENTION(S):
      Immunohistochemistry for human type I, III, and IV collagen with specific
      monoclonal antibodies was used for analysis. MAIN OUTCOME MEASURE(S): Expression
      of type I, III, and IV collagen. RESULT(S): Immunohistochemical staining for type
      I and III collagen revealed intense staining of the CL stroma during early
      pregnancy, as compared with those in the menstrual cycle. Moreover, pericellular
      intense immunostaining for type IV collagen was observed around the luteal cells,
      especially luteal granulosa cells, of early pregnancy. CONCLUSION(S): These
      results suggest that alterations in distribution of collagen might play an
      important role in determining the physiology and structure of the CL during the
      menstrual cycle and early pregnancy.

PMID- 16616080
TI  - Hypoxia regulates vascular endothelial growth factor and soluble fms-like
      tyrosine kinase-1 secretion by human oviductal epithelial cells and stromal
      fibroblasts.
AB  - OBJECTIVE: To evaluate the effect of hypoxia on the production of vascular
      endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)
      in the human fallopian tube. DESIGN: The secretion of VEGF and sFlt-1 by cultured
      oviductal epithelial cells (OECs) and oviductal stromal fibroblasts (OSFs) in
      response to hypoxia was investigated. SETTING: Research laboratory at a medical
      school. PATIENT(S): Normal oviducts obtained from seven premenopausal patients
      were used. INTERVENTION(S): Oviductal epithelial cells and OSFs were incubated
      under normoxic (20% O2) or hypoxic (2% O2) conditions. MAIN OUTCOME MEASURE(S):
      The concentrations of VEGF and sFlt-1 in the culture media of OECs and OSFs were
      measured by enzyme-linked immunosorbent assays. RESULT(S): The secretion of both
      VEGF and sFlt-1 was detected in cultured OECs and OSFs and was found to have been
      stimulated under hypoxic conditions in these cells. CONCLUSION(S): The present
      findings suggest that hypoxia in the local environment may stimulate oviductal
      vascular permeability by inducing the production of VEGF by oviductal cells.
      Simultaneous up-regulation of sFlt-1 secretion by these cells under hypoxic
      conditions may prevent excessive up-regulation of vascular permeability. The
      modulation of the bias of VEGF and sFlt-1 in the fallopian tubes may contribute
      to the normal and pathological processes of oviductal fluid secretion by
      regulating oviductal vascular permeability during the menstrual cycle.

PMID- 16616081
TI  - An alternative method of deriving embryonic stem cell-like clones by aggregation
      of diploid cells with tetraploid embryos.
AB  - OBJECTIVE: To assess whether embryonic stem (ES) cells could be derived from the
      aggregation of diploid cells with tetraploid embryos. DESIGN: Randomized,
      prospective study. SETTING: University embryology and gamete biotechnology
      laboratory. ANIMAL(S): F1 (C57BL6/DBA2) mice. INTERVENTION(S): Four- to eight
      cell F1 tetraploid embryos were aggregated with 10 to 15 donor E14 ES cells. MAIN
      OUTCOME MEASURE(S): Embryogenesis and ES cell establishment. RESULT(S): No
      difference (78% to 89%) in blastocyst formation was detected between the
      aggregated tetraploid and the control diploid embryos. In a total of 27
      transfers, pregnancy was detected in three tetraploid (23.1%) and five diploid
      (35.7%) cases, and three live births developed from the aggregated tetraploid
      embryos. The tetraploid blastocysts without aggregation were plated, but no ES
      cell-like colony was formed. Six of eight aggregated blastocysts derived well
      proliferated colonies, which were positive for anti-stage-specific embryonic
      antigen (SSEA)-1 antibody, Oct-4, and alkaline phosphatase. The microsatellite
      assay confirmed the homogenous makeup among the donor E14 cells and live-birth
      and ES-like cells derived from the E14-aggregated, tetraploid embryo.
      CONCLUSION(S): The aggregation of pluripotent diploid cells with tetraploid
      embryos yielded live births and ES-like cells that were homogenous to the donor
      diploid cells.

PMID- 16616082
TI  - Effect of dexamethasone on germ cell apoptosis in the contralateral testis after
      testicular ischemia-reperfusion injury in the rat.
AB  - OBJECTIVE: To evaluate the effect of dexamethasone on spermatogenesis and germ
      cell apoptosis in the ipsilateral and contralateral testis after testicular
      ischemia-reperfusion (IR) in rats. DESIGN: Laboratory study. SETTING: Medical
      research laboratory in a university setting. ANIMAL(S): Forty adult Sprague
      Dawley rats weighing 250-280 g. INTERVENTION(S): Testicular IR, treatment with
      dexamethasone (10 mg per kilogram of body weight). MAIN OUTCOME MEASURE(S):
      Testicular germ cell apoptosis was assessed by deoxyuridine nick-end labeling
      immunohistochemical assay. RESULT(S): Testicular ischemia in rats led to
      histological damage in the ipsilateral testis. In the contralateral testis,
      minimal damage was observed. Germ cell apoptosis in both the ischemic and the
      contralateral testis increased significantly after IR. Treatment with
      dexamethasone did not change germ cell apoptosis in ischemic testis but decreased
      germ cell apoptosis in the contralateral testis. CONCLUSION(S): Glucocorticoids
      may be beneficial for spermatogenesis after testicular IR by decreasing germ cell
      apoptosis in the contralateral testis.

PMID- 16616083
TI  - Regulation of cyclooxygenase activity in cultured endometrial stromal cells by
      granulocyte-macrophage colony-stimulating factor.
AB  - OBJECTIVE: To assess the ability of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) to regulate cyclooxygenase (COX) enzyme activity and
      prostaglandins (PGs) synthesis, specifically PGE2 production in stromal cells,
      neither of which have been addressed in the literature. DESIGN: Prospective
      study. SETTING: Department of obstetrics and gynecology at a university hospital.
      PATIENT(S): Human luteal phase endometrium was obtained from surgical specimens
      (n = 6) for clinical indications. INTERVENTION(S): Confluent stromal cells were
      stimulated with GM-CSF. MAIN OUTCOME MEASURE(S): Expression of COX mRNA, COX
      enzyme activity, and PGE2 level in cultured stromal cells. RESULT(S): Confluent
      stromal cell cultures treated with P and E2 for 9 days were stimulated with GM
      CSF. After treatment of 12 hours, low-dose GM-CSF (0.001-0.1 ng/mL) increased COX
      2 mRNA levels in stromal cell, whereas high dose GM-CSF (1-100 ng/mL) decreased
      COX-1 and COX-2 mRNA levels. After treatment of 48 hours, low concentrations of
      GM-CSF (0.001-0.1 ng/mL) increased total COX and COX-2 enzyme activity, whereas
      high concentrations of GM-CSF (1-100 ng/mL) inhibited COX and COX-2 activity; The
      PGE2 levels decreased by 31% to 393.3 pg/mL (P < .05) with concentrations of GM
      CSF increasing from 1 ng/mL to 100 ng/mL. CONCLUSION(S): There appeared to be a
      biphasic pattern of COX-2 enzyme response to GM-CSF with low concentrations
      increasing activity and high concentrations inhibiting activity. It is possible
      that GM-CSF may provide critical regulation of PG production in the
      preimplantation period.

PMID- 16616084
TI  - Potential role of toll-like receptor 3 in a murine model of polyinosinic
      polycytidylic acid-induced embryo resorption.
AB  - OBJECTIVE: To investigate the potential role that toll-like receptor 3 (TLR3) may
      play in a murine model of polyinosinic-polycytidylic acid (polyIC)-induced embryo
      resorption. DESIGN: An animal model-based study on induced embryo resorption.
      SETTING: University animal laboratory. ANIMAL(S): Pathogen-free animals housed
      under barrier conditions and monitored for health status. Pregnant BALB/c mouse
      mated by C57BL/6 male was used as a model of allogeneic gestation.
      INTERVENTION(S): The administration of polyIC was performed to establish a murine
      model of induced embryo resorption, with or without TLR3 blocking by multiple
      injection of mAb against this receptor. MAIN OUTCOME MEASURE(S): Flow cytometric
      analysis was performed to detect the percentage of CD45(+)DX5+ and DX5(+)CD69+
      cell subsets, with the DX5 antigen used as a common natural killer (NK) cell
      marker, and CD69 as a marker for activated NK cells, respectively. RESULT(S): In
      the allogeneic mating model, BALB/cxC57BL/6, both the CD45(+)DX5+ and DX5(+)CD69+
      cell percentages were significantly elevated upon polyIC stimulation at the
      absence of anti-TLR3 administration but were kept unchanged if the female mice
      were pretreated with anti-TLR3 monoclonal antibody. Accordingly, the resorption
      rate of embryos was boosted by polyIC administration, but this effect could be
      abrogated by pretreatment of anti-TLR3 mAb. CONCLUSION(S): The engagement of
      polyIC with TLR3 may be critical to the activation of NK cells infiltrated at the
      feto-maternal interface, subsequently resulting in an increase in embryo
      resorption.

PMID- 16616085
TI  - Morphological and ultrastructural evaluation of cultured frozen-thawed human
      fetal ovarian tissue.
AB  - OBJECTIVE: To investigate a defined culture condition for the culture of frozen
      thawed human ovarian tissue. DESIGN: Prospective laboratory study. SETTING:
      Reproductive biology laboratories in university hospitals. PATIENT(S): Fetal
      ovarian tissue from elective termination of pregnancy. INTERVENTION(S): Culture
      of frozen-thawed fetal ovarian tissue for up to 63 days. MAIN OUTCOME MEASURE(S):
      Morphology, morphometry, and survival of follicles in relation to culture times.
      RESULT(S): The proportion of primordial, early primary, and primary follicles in
      frozen-thawed (day 0) ovarian tissue was 77.5%, 21.7%, and 0.8%, respectively.
      Pronounced degeneration was found in all cell types, and < or =36% of the
      follicles had signs of atresia at days 7-14, but this figure improved with
      culture time to <20% of the total follicular population. After 7-14 and 21-35
      days of culture, the relative proportion of the follicles in the different
      classes remained nearly stable. Morphometric examination of healthy follicles
      showed a significant increase in both follicle and oocyte diameter compared with
      control. A few follicles had developed to the early secondary stage.
      Ultrastructural analysis demonstrated well-preserved morphological integrity of
      healthy primordial and early primary follicles. Immunohistochemical localization
      of proliferating cell nuclear antigen was positive in proliferating follicular
      cells at days 7-14 and 21-35 of culture. CONCLUSION(S): The present culture
      condition leads to good survival and progressive follicular growth and
      differentiation that is comparable to the physiological pattern of early
      folliculogenesis.

PMID- 16616086
TI  - A heparin-binding membrane protein from goat spermatozoa immobilizes spermatozoa
      in the presence of complement.
AB  - OBJECTIVE: To characterize the major membrane protein of goat spermatozoa.
      DESIGN: Basic research. SETTING: Samples collected from local slaughterhouse and
      study conducted in an academic research environment. PATIENT(S): Goat epididymal
      tissue. INTERVENTION(S): Goat epididymal tissues were collected immediately after
      slaughter and the spermatozoa were isolated within 2 hours. Sperm immobilization
      test was performed with motile spermatozoa at 32 degrees C within 3-4 hours of
      collection and isolation of the cells. MAIN OUTCOME MEASURE(S): The heparin
      binding sperm membrane protein (HBSM) of goat is insensitive to trypsin and its
      antisera immobilize spermatozoa in presence of complement. RESULT(S): Forty-two
      percent of membrane protein could be extracted with 0.25% (wt/vol) 3-[(3
      Cholamidopropyl) dimethylammonio]-1-propanesulfonate (CHAPS) from the isolated
      sperm membrane. By heparin-affinity chromatography, 46% of the extracted protein
      was recovered. Positive hybridization with radiolabeled heparin on western
      transfer confirmed the heparin-binding property of the protein (HBSM). Heparin
      binding to HBSM is an ionic bondage and can be disrupted by 1 M NaCl, as revealed
      by 86% recovery of the radiolabeled heparin in trichloroacetic acid-precipitated
      supernatant of [(125)I] heparin-HBSM conjugate. Heparin-binding sperm membrane
      protein is localized at the anterior region of the spermatozoal head. No
      detectable proteolytic fragment of HBSM was detected after limited digestion by
      trypsin. Heparin-binding sperm membrane protein antisera (1:10,000 titer)
      developed from rabbit did not recognize the denatured protein. The antisera
      inhibited spermatozoal motility in a complement-dependent manner. CONCLUSION(S):
      We suggest that the heparin-binding motif of the spermatozoal membrane protein
      might be required in modulation of the spermatozoal motility.

PMID- 16616087
TI  - Efficiency of equilibrium cooling and vitrification procedures for the
      cryopreservation of ovarian tissue: comparative analysis between human and animal
      models.
AB  - OBJECTIVE: To compare the efficiency of equilibrium cooling and vitrification for
      cryopreservation of human ovarian tissue and to determine the best experimental
      model for developing new protocols. DESIGN: Experimental prospective study.
      SETTING: An academic research environment. PATIENT(S) AND ANIMAL(S): Human
      ovarian biopsy specimens were obtained from three women undergoing operative
      laparoscopy for ovarian cyst enucleation. Adult cow and pig ovaries, collected at
      the abattoir. INTERVENTION(S): Ovarian tissue fragments of three individuals for
      each species were cryopreserved by using two protocols, either for equilibrium
      cooling or vitrification. MAIN OUTCOME MEASURE(S): Comparison between fresh and
      cryopreserved tissue of primordial, primary, and secondary follicle morphology,
      graded in three classes. RESULT(S): Human and bovine follicles responded in the
      same way to the two equilibrium cooling protocols, whereas pig tissue was more
      cryoresistant. Both vitrification protocols caused extensive damage to the tissue
      of all species. Human tissue showed a response to vitrification that was
      different from that of both animal species. CONCLUSION(S): Bovine is a good
      animal model for the development of human ovarian tissue cryopreservation
      protocols by equilibrium cooling procedures. Vitrification is less efficient than
      equilibrium cooling, and at present, neither bovine nor pig can be considered
      relevant animal models for human tissue.

PMID- 16616088
TI  - Local application of danazol-loaded hyaluronic acid hydrogel to endometriosis in
      a rat model.
AB  - OBJECTIVE: To evaluate the efficacy of a drug delivery system composed of danazol
      loaded hyaluronic acid for local application to endometriosis. DESIGN:
      Prospective, randomized study. SETTING: Academic research unit of the department
      of obstetrics and gynecology in a university hospital. PATIENT(S): Adult female
      Sprague-Dawley rats. INTERVENTION(S): Danazol-loaded hyaluronic acid hydrogel (DZ
      HA gel) was injected into the rat endometriosis model. MAIN OUTCOME MEASURE(S):
      Size and histological changes in experimental endometriosis, the concentration of
      danazol in the cyst wall and plasma, and estrous cycles were examined. RESULT(S):
      Histologically, DZ-HA gel-treated cysts displayed marked atrophy of the
      endometrial epithelium. Increased numbers of apoptotic cells and decreased
      numbers of proliferative cells were noted with 10 mg/mL DZ-HA gel. Size of
      treated cysts decreased to approximately 60% at 9 weeks after injection. The
      estrous cycles were not disturbed during DZ-HA gel treatment. CONCLUSION(S):
      Local injection of DZ-HA gel achieved endometrial atrophy of an experimental
      model of endometriosis without disturbing the sexual cycle. These results suggest
      that local application of DZ using this drug delivery system may prove useful for
      treating endometriosis.

PMID- 16616089
TI  - The Fas system may have a role in male reproduction.
AB  - OBJECTIVE: To assess what the distributions of Fas system proteins are in normal
      rat testicular tissue; to assess whether there is a change in these distributions
      and in expression levels with experimentally-induced varicocele of 9, 11, and 13
      weeks; and to assess whether there is a relationship between apoptosis and the
      Fas system in varicocele-induced rat testis. DESIGN: Comparative and controlled
      study. SETTING: University animal care and operation unit. ANIMAL(S): Wistar male
      rats for experimental and control groups. INTERVENTION(S): The control group
      underwent sham operation (n = 6). Rats in experimental groups underwent partial
      ligation of the renal vein to induce an experimental varicocele and then were
      killed at 9 (n = 6), 11 (n = 6), and 13 (n = 6) weeks after induction of
      varicocele. MAIN OUTCOME MEASURE(S): Tissues were fixed and processed for
      paraffin and Araldite embedding, and subsequently immunohistochemistry, terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling, and transmission electron microscopy were performed. In addition,
      Western blotting was applied. RESULT(S): In control testis, we detected the
      expression of FasL in spermatids, interestingly at the progressing stages of
      acrosome formation and in the heads of the spermatozoa being released to lumen.
      Varicocele induction revealed a significant down-regulation of this protein,
      especially 11 weeks after the operation, without altering its distribution. Fas
      protein was present in cytoplasmic extrusions of the elongated spermatids and
      evidently in Leydig cells of the interstitial tissue. The expression of Fas
      protein was diminished after 11 weeks of varicocele induction, both in Leydig
      cells and in cytoplasmic extrusions. The decrease of Fas was significant in the
      13-week-old varicocele group, whereas that of FasL was significant in the 11-week
      old varicocele group. Compared with sham-operated animals, a minor increase in
      the number of apoptotic germ cells in varicocele groups was detected.
      CONCLUSION(S): Our results exposed other possible important roles of the Fas
      system in addition to than apoptosis in male reproduction. We suggest that the
      role of the Fas system needs further investigation both in animal models and in
      human male infertility.

PMID- 16616090
TI  - Effects of soy on the mammary glands of premenopausal female monkeys.
AB  - OBJECTIVE: To evaluate the interactive effects of dietary soy and menstrual cycle
      phase on breast proliferation, apoptosis, and sex steroid receptor expression in
      premenopausal female cynomolgus monkeys. DESIGN: Animals were randomized to
      receive diets with either casein lactalbumin or soy as the protein source for 12
      months. Paired follicular and luteal mammary gland biopsies were taken before and
      after treatment and evaluated for epithelial proliferation and area, apoptosis,
      and sex steroid receptor expression. SETTING: Academic research environment.
      ANIMAL(S): Fifty-two adult female cynomolgus monkeys (Macaca fascicularis).
      INTERVENTION(S): Soy protein with the human equivalent of 129 mg/d of
      isoflavones. MAIN OUTCOME MEASURE(S): Breast proliferation and epithelial area.
      RESULT(S): Follicular and luteal assessments were taken on cycle day (+/- SE) 5.3
      +/- 0.1 and 22.0 +/- 0.1, respectively. Serum E2, serum P, breast proliferation,
      and vaginal maturation were significantly higher in the luteal vs. follicular
      phase. Soy treatment resulted in significantly higher serum isoflavone
      concentrations compared with the casein lactalbumin group but did not
      significantly affect breast proliferation, epithelial area, apoptosis, or
      progesterone receptor expression; uterine size; or vaginal maturation in either
      the follicular or luteal phase. CONCLUSION(S): Results indicate that dietary
      levels of soy intake have no detectable hormonal effects on the premenopausal
      breast.

PMID- 16616091
TI  - Arsenite induces aberrations in meiosis that can be prevented by coadministration
      of N-acetylcysteine in mice.
AB  - OBJECTIVE: To evaluate in vitro effects of arsenite and of arsenite plus N
      acetylcysteine on mouse oocyte meiosis. DESIGN: Morphological study using mouse
      oocytes submitted to in vitro maturation (IVM). SETTING: Laboratory of
      reproductive biology. ANIMAL(S): Six-week-old CD-1 mice superovulated with
      pregnant mare serum gonadotropin. INTERVENTION(S): During IVM, mouse oocytes were
      exposed to arsenite alone or to arsenite plus N-acetylcysteine. MAIN OUTCOME
      MEASURE(S): Meiotic anomalies were assessed using immunofluorescence microscopy
      and PolScope (Cambridge Research and Instrumentation, Boston, MA) imaging.
      RESULT(S): In vitro arsenite administration produced dose-dependent and time
      dependent meiotic anomalies, characterized by spindle disruption or chromosome
      misalignment. After 12-14 hours of IVM, exposure to 2 microg/mL of arsenite for
      12-14 hours or to 8 microg/mL of arsenite for 2 hours arrested oocyte maturation
      at the germinal vesicle or germinal-vesicle breakdown stage. Exposure to 4
      microg/mL of arsenite for 2 hours arrested oocyte maturation at metaphase I stage
      in 95% of exposed oocytes (80% exhibiting abnormalities) after 12-14 hours in
      IVM. After 12-14 hours in IVM, of the oocytes exposed to 2 microg/mL of arsenite
      for 2 hours, only 15% reached the meiosis II stage (5% exhibiting abnormalities).
      After 15-17 hours in IVM, however, of the oocytes exposed to 2 microg/mL of
      arsenite for 2 hours, 65.2% reached the meiosis II stage (43.5% exhibiting
      abnormalities). Co-administration of N-acetylcysteine prevented the arsenite
      induced meiotic abnormalities and the delayed IVM. CONCLUSION(S): In vitro
      arsenite exposure caused meiotic abnormalities that were prevented by co
      administration of N-acetylcysteine, suggesting that arsenite-induced meiotic
      aberrations are mediated by reactive oxygen species.

PMID- 16616092
TI  - Androgenic and antiandrogenic effects and expression of androgen receptor in
      mouse embryonic stem cells.
AB  - OBJECTIVE: To investigate the effects of androgen and antiandrogen and the
      expression of androgen receptor on mouse embryonic stem cells (ESCs) and the
      inner cell mass. DESIGN: Controlled laboratory study. SETTING: Academic
      university hospital. ANIMAL(S): Blastocysts from mice developed at the Institute
      for Cancer Research and 129/Sv mice embryonic stem cell line. INTERVENTION(S):
      Cultured mouse ESCs were exposed to testosterone (T), dihydrotestosterone (DHT),
      or the antiandrogen nilutamide. MAIN OUTCOME MEASURE(S): Immunohistochemistry for
      androgen receptor (AR), quantitative real-time polymerase chain reaction
      analysis, cell colorimetric assays, and Western blot analysis. RESULT(S):
      Androgen receptor messenger RNA (mRNA) was first detected both in the inner cell
      mass from blastocysts and in undifferentiated ESCs. It increased stage
      dependently during ESC differentiation. Although both T and DHT had marginal
      effects on AR mRNA expression level and cell growth in vitro, the nonsteroidal
      antiandrogen nilutamide significantly stimulated ESC growth and induced Akt
      expression. The enhancing effects of nilutamide on mouse ESCs indicated that the
      Akt pathway may be involved in nilutamide-promoted ESC growth. CONCLUSION(S):
      These findings provide the first evidence of the existence of AR in ESCs. During
      differentiation, the expression level of AR was increased in a stage-dependent
      but not a ligand-dependent manner. Nilutamide promoted cell growth and increased
      Akt expression in ESCs.

PMID- 16616093
TI  - p16, retinoblastoma (pRb), and cyclin D1 protein expression in human
      endometriotic and adenomyotic lesions.
AB  - OBJECTIVE: To investigate the expression of p16, retinoblastoma (pRb), and cyclin
      D1 oncoproteins in endometriomas and adenomyosis. DESIGN: Immunohistochemical
      study for p16, pRb, and cyclin D1 proteins in formalin-fixed paraffin-embedded
      endometriotic and adenomyotic tissues. SETTING: University hospital. PATIENT(S):
      Tissues from 25 women with endometriomas and 31 women with adenomyosis were
      evaluated. INTERVENTION(S): Tissue samples were collected during gynecologic
      surgery and confirmed by histology to have endometriosis or adenomyosis. Nuclear
      expression of p16, pRb, and cyclin D1 proteins was examined by
      immunohistochemistry. MAIN OUTCOME MEASURE(S): Distribution and intensity of
      immunostaining. RESULT(S): In the proliferative phase of the cycle, p16 was
      detected in 77% of adenomyosis tissues but in only 15% of endometriosis tissues.
      Moreover, in adenomyosis samples positive for p16, 100% of the adenomyotic cells
      expressed p16, whereas only 10%-20% of endometriosis cells from positive cases
      expressed p16. In contrast, pRb was detected in 28% of endometriosis cases but
      not in any adenomyotic tissues. Cyclin D1 was absent in both endometriotic and
      adenomyotic tissue samples. CONCLUSION(S): Differences in oncoprotein expression
      between endometriotic and adenomyotic tissues provide further evidence that the
      pathogenesis of endometriosis is different from that of adenomyosis.

PMID- 16616094
TI  - Orthotopic microvascular reanastomosis of whole cryopreserved ovine ovaries
      resulting in pregnancy and live birth.
AB  - OBJECTIVE: To evaluate the feasibility of contralateral autotransplantation of
      cryopreserved whole ovaries with microanastomosis of the ovarian vascular
      pedicle. DESIGN: Animal study. SETTING: Department of Biomedical Sciences,
      General Hospital of Vienna, Austria. ANIMAL(S): Nine ewes, six month of age.
      INTERVENTION(S): Laparotomic unilateral oophorectomy was performed. Ovaries were
      frozen using a controlled-rate freezing system. After frozen storage,
      contralateral laparotomic oophorectomy was performed, and the thawed ovaries were
      returned to the contralateral orthotopic site with microsurgical vascular
      anastomosis. MAIN OUTCOME MEASURE(S): Histologic examination and serum follicle
      stimulating hormone and progesterone levels. RESULT(S): Four sheep showed
      postoperative luteal function. One sheep conceived after spontaneous intercourse
      and delivered a healthy lamb 545 days after transplantation. Histologic
      examination of the ovaries 18-19 months after transplantation showed that the
      structural integrity of the ovarian stroma had largely been retained in six out
      of nine animals. Follicular survival rate in the grafted ovaries was 1.7%-7.6%.
      CONCLUSION(S): Microvascular anastomosis of whole ovaries and orthotopic
      transplantation after cryopreservation is technically feasible and a promising
      procedure in ovarian tissue banking.

PMID- 16616095
TI  - Lycopene prevents adriamycin-induced testicular toxicity in rats.
AB  - OBJECTIVE: To investigate a possible protective role of lycopene on adriamycin
      (ADR)-induced spermiotoxicity using quantitative, biochemical and
      histopathological approaches. DESIGN: Experimental study. SETTING: Firat
      University Medical School, Experimental Research Centre, Elazig, Turkey. ANIMALS:
      Twenty four Sprague Dawley rats (8-weeks old) INTERVENTION(S): Adriamycin (10 mg
      kg(-1)) was intraperitoneally injected and lycopene (4 mg kg(-1)) was
      administered by gavage in corn oil. MAIN OUTCOME MEASURE(S): Reproductive organ
      weights were evaluated along with epididymal sperm concentration, motility and
      morphology. Testicular histological findings, oxidative status and plasma
      testosterone levels were also determined. RESULT(S): Lycopene ameliorated ADR
      induced reductions in both testes and epididymis weights. ADR decreased sperm
      motility, increased total abnormal sperm rates, but epididymal sperm
      concentration was not changed compared to control. A marked normalization was
      achieved in sperm motility and morphology in pretreatment with lycopene. Although
      testosterone level was decreased in ADR group compared to control, no changes
      were observed in pretreatment group. An increase in malondialdehyde and a
      decrease reduced glutathione concentrations were detected in alone ADR group
      compared to control. Pretreatment with lycopene restored significantly
      malondialdehyde and reduced glutathione concentrations. ADR caused severe
      degenerative changes in germinative cells, atrophy in the diameter size of
      seminiferous tubules and germinative cell thickness. However, ADR-induced
      histopathological alterations were effectively reverted by pretreatment with
      lycopene. CONCLUSION(S): This study clearly indicates that ADR treatment markedly
      impaired testicular function and that pretreatment with lycopene might prevent
      this toxicity.

PMID- 16616096
TI  - Extract of Azadirachta indica (neem) leaf induces apoptosis in rat oocytes
      cultured in vitro.
AB  - OBJECTIVE: To determine whether aqueous neem leaf extract (NLE) could induce
      degeneration of rat oocytes and, if so, whether apoptosis is involved during NLE
      induced degeneration of oocytes cultured in vitro. DESIGN: A controlled
      prospective study. SETTING: Laboratory research setting at Department of
      Reproductive Biomedicine of the Institute. ANIMAL(S): Fifty-four sexually
      immature female rats that were 24-25 days of age. INTERVENTION(S): The immature
      female rats were injected with 10 IU pregnant mare serum gonadotropin for 48 h
      followed by 10 IU human chorionic gonadotropin (hCG) for 16 h. After 16 h, the
      rats were killed and ovulated cumulus oocyte complexes were collected from the
      oviduct. Cumulus-enclosed as well as denuded oocytes were used in the present
      study. MAIN OUTCOME MEASURE(S): Rates of shrinkage, membrane leakage,
      degeneration, assessment of morphological apoptotic changes, bax protein
      expression, and DNA fragmentation. RESULT(S): The NLE induced morphologic
      apoptotic changes such as shrinkage, membrane leakage, and cytoplasmic
      fragmentation prior to degeneration of oocytes. The NLE-treated oocytes that had
      morphologic apoptotic features showed overexpression of bax protein and DNA
      fragmentation as evidenced by terminal deoxynucleotidyl transferase nick-end
      labeling-positive staining and DNA ladder pattern. CONCLUSION(S): Neem leaf
      extract induced apoptosis in rat oocytes prior to degeneration in vitro.

PMID- 16616097
TI  - Human embryo-conditioned medium stimulates in vitro endometrial angiogenesis.
AB  - OBJECTIVE: Successful implantation and placentation depend on the interaction
      between the endometrium and the embryo. Angiogenesis is crucial at this time. In
      this article we investigate the direct influence of the human embryo on in vitro
      endometrial angiogenesis. DESIGN: In vitro study. SETTING: Human endometrial
      microvascular endothelial cells (hEMVEC) grown on an in vitro angiogenesis model.
      INTERVENTION(S): Conditioned media (CM) of human embryos were used to stimulate
      in vitro angiogenesis. MAIN OUTCOME MEASURE(S): In vitro angiogenesis of hEMVEC.
      RESULT(S): Conditioned media of human embryos, containing significant amounts of
      vascular endothelial growth factor (VEGF)-A, as determined by enzyme-linked
      immunosorbent assay (ELISA), caused an increase in hEMVEC tube formation. This
      effect was prevented by soluble VEGF receptor 1, which quenches VEGF-A activity.
      Recombinant EGF alone and leukemia inhibitory factor in combination with VEGF-A
      stimulated hEMVEC tube formation. None of the other tested recombinant mediators,
      which have been described as produced by the early embryo/trophoblast
      (interleukin (IL) 10, transforming growth factor (TGF) beta, placental growth
      factor, hCG, colony-stimulating factor 1, interferon-gamma, insulin-like growth
      factor I and II, IL-6, platelet-derived growth factor, and TGFalpha), had an
      effect on tube formation by hEMVEC. CONCLUSION(S): For the first time, it is
      shown that the human embryo is able to stimulate in vitro endometrial
      angiogenesis at the time of implantation, a process that is mediated by VEGF-A.

PMID- 16616098
TI  - Localization and quantitative expression of the calcium-sensing receptor protein
      in human oocytes.
AB  - OBJECTIVE: To investigate the expression of the calcium-sensing receptor (CaSR)
      protein in human oocytes at the germinal vesicle (GV) and metaphase I (MI) and II
      (MII) stages. DESIGN: Prospective study. SETTING: Academic basic research
      laboratory and hospital-based fertility center. PATIENT(S): Immature and
      supernumerary mature oocytes (n = 118) excluded from intracytoplasmic sperm
      injection treatment. INTERVENTION(S): Immunofluorescence and Western blot with a
      primary antibody against human CaSR. Confocal laser scanning microscopy (CLSM)
      together with quantitative image analysis used to measure the fluorescence
      intensity variations in oocytes at GV, MI, and MII stages. MAIN OUTCOME
      MEASURE(S): The CaSR expression pattern as evaluated by immunostaining in denuded
      oocytes and cumulus cells, CLSM, and three-dimensional image reconstructions;
      quantitative analysis at the equatorial plane of the oocyte. RESULT(S): We
      identified CaSR in human oocytes and cumulus cells. The fluorescence intensity
      within the oocyte varied with the developmental stage, with the greatest increase
      at the MI stage. CONCLUSION(S): The present study demonstrates for the first time
      the expression and localization of CaSR protein in human oocytes. Increased CaSR
      protein expression in the MI stage suggests that it may be involved in the
      regulation of human oocyte development and maturation.

PMID- 16616099
TI  - Evaluation of the embryonic preimplantation potential of human adult somatic
      cells via an embryo interspecies bioassay using bovine oocytes.
AB  - OBJECTIVE: To examine the embryonic preimplantation potential of human adult
      somatic cells by creating interspecies embryos via somatic cell nuclear transfer
      (SCNT) using bovine oocytes. DESIGN: Prospective study. SETTING: Research
      facility of Reprogen. PATIENT(S): Infertile couples. INTERVENTION(S): Enucleated
      bovine oocytes were fused via SCNT with either human granulosa (HG) or fibroblast
      (HF) cells and cultured in vitro. Polymerase chain reaction (PCR) and DNA
      analysis were performed on the interspecies embryos. Parthenogenetically
      activated embryos served as controls. MAIN OUTCOME MEASURE(S): Embryonic
      preimplantation development after interspecies SCNT. RESULT(S): From enucleated
      bovine oocytes fused with HG cells (n = 48) and HF cells (n = 75), 15 HG- and 22
      HF-derived embryos developed, some of which progressed to blastocysts (31.3% vs.
      29.3%, respectively). The PCR and DNA analysis showed that the interspecies
      embryos contained human genomic DNA specific for the individual DNA profile of
      the HG or HF donor cells used for SCNT. In addition, both bovine- and human
      specific mitochondrial DNA was detectable in the interspecies embryos up to the
      blastocyst stage. Parthenogenetic development was 46.8% and 64.9% for the HG and
      HF series, respectively. The SCNT efficiency index, defined as the ratio of SCNT
      and parthenogenetic success rate, was 66.8% for HG cells and 45.5% for HF cells.
      CONCLUSION(S): This interspecies bioassay can be utilized to determine and assess
      the embryonic preimplantation potential of different types of human adult somatic
      cells.

PMID- 16616100
TI  - Effects of fibrin sealant on single-layer uterine incision closure in the New
      Zealand white rabbit.
AB  - OBJECTIVE: To determine if the addition of fibrin sealant to incision closure in
      a rabbit uterine horn myomectomy model affects adhesion formation or strength of
      incision closure. DESIGN: Prospective randomized controlled trial. SETTING:
      Academic research center. ANIMAL(S): New Zealand white female rabbits.
      INTERVENTION(S): A pilot study revealed that the time interval for maximal
      uterine incision healing was eight weeks. Thirty New Zealand white rabbits
      underwent a 1-cm standardized myotomy incision on both uterine horns. A single
      interrupted stitch of 3-0 polygalactin suture was placed to reapproximate each
      incision. Fibrin sealant was then applied to one of each rabbit's horns
      (randomized). After eight weeks, the rabbits were killed, and the strength of
      myotomy closure was determined by measurement of maximal burst pressure for each
      uterine horn. Adhesion presence was recorded. MAIN OUTCOME MEASURE(S): Uterine
      burst pressure, adhesion presence. RESULT(S): The mean burst pressure was 267.8
      (+/-75.8) mm Hg in the suture only group and 247.8 (+/-92.3) mm Hg in the suture
      and fibrin sealant group. There was no statistical difference in the presence of
      adhesions. CONCLUSION(S): Fibrin sealant did not strengthen myotomy repair nor
      did it reduce postoperative adhesion formation. There is no apparent advantage to
      fibrin sealant in this myomectomy model.

PMID- 16616101
TI  - Increased expression of interleukin-1alpha and interleukin-1beta is associated
      with experimental varicocele.
AB  - OBJECTIVE: To describe the effect of varicocele, in an experimental rat model, on
      the levels of IL-1alpha and IL-1beta proteins in testis tissue. DESIGN:
      Comparative and controlled study. SETTING: Experimental research. ANIMAL(S):
      Wistar male rats in experimental and control groups. INTERVENTION(S): The control
      group underwent sham operation (n = 6). Experimental groups underwent partial
      ligation of the renal vein to induce experimental varicocele and were then killed
      at 9 (n = 6), 11 (n = 6), and 13 (n = 6) weeks after induction of varicocele.
      MAIN OUTCOME MEASURE(S): Histologic evaluation of the varicocele model was
      determined by periodic acid-Schiff staining of paraffin-embeded testicular
      tissues. Levels of cytokines were assessed by immunohistochemistry and Western
      blot analysis. RESULT(S): Varicocele caused testicular damage, especially in 11-
      and 13-week-old varicocele groups. In sham-operated rats, Golgi complexes of
      round spermatids expressed especially the alpha form of IL-1. By the progression
      of varicocele, the IL-1alpha expression increased temporally in Sertoli cells,
      spermatogonia, primary spermatocytes, spermatids, and Leydig cells. The
      expression of IL-1beta was seen in Leydig cells in sham-operated rats. The IL
      1beta expression was also increased upon progression of varicocele in Leydig
      cells, Sertoli cells, and spermatogonia. CONCLUSION(S): We suggest that IL-1alpha
      and IL-1beta are the regulators of testicular function. Certain pathologic
      conditions, e.g., varicocele, cause an increase in the expressions of such
      proinflammatory cytokines. The increased expression of IL-1alpha and IL-1beta in
      varicocele shifts the balance in favor of inflammatory and immune responses and
      causes detrimental effects in testis tissue, which may cause male infertility.

PMID- 16616102
TI  - Expression and hormonal modulation of the thromboxane A2 receptor gene in
      mammalian testicular arteries.
AB  - OBJECTIVE: Thromboxane A2 (TXA2) is a biologically potent arachidonate metabolite
      which causes vasoconstriction and platelet aggregation. This study aimed to
      evaluate the presence of TXA2 receptors in mammalian testicular arteries and the
      influence of exogenous gonadotropin administration on their expression. DESIGN:
      Experimental study. SETTING: Experimental animals in an academic research
      environment. ANIMAL(S): Seven rams aged 4-6 years, weighing 60-90 kg.
      INTERVENTION(S): Both testicular arteries of seven rams were extracted before
      (from one testis) and after (from the opposite testis) IV administration of 5,000
      IU human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURE(S): The expression of
      the TXA2 receptor gene was investigated by the real-time polymerase chain
      reaction. Data were analyzed by means of Student t test. Results were expressed
      as mean +/- standard deviation. A P value of <.01 was considered statistically
      significant. RESULT(S): Polymerase chain reaction revealed the presence of TXA2
      messenger RNA receptor in all the basal samples, but the expression of TXA2
      receptor gene was undetectable in all the arteries obtained 24 h after the
      administration of hCG. CONCLUSION(S): These preliminary results demonstrated for
      the first time the presence of TXA2 receptors in mammalian testicular arteries.
      Results also showed that their expression was down-regulated after hCG
      administration.

PMID- 16616103
TI  - Expression of a fluorescent recombinant form of sperm protein phospholipase C
      zeta in mouse epididymal sperm by in vivo gene transfer into the testis.
AB  - OBJECTIVE: To use in vivo gene transfer into the testis by electroporation to
      express a fluorescent recombinant form of a testis-specific gene in the mature
      epididymal sperm of mice and thus study the pattern of gene localization. DESIGN:
      Controlled animal study. SETTING: Research laboratory at the University of
      Oxford. ANIMAL(S): Four- to 6-week-old male mice. INTERVENTION(S): Phospholipase
      C zeta (PLCzeta), the putative mammalian egg activation factor, was fused to
      enhanced yellow fluorescent protein (EYFP), and in vivo gene transfer by
      electroporation was used to introduce this transgene (PLCzeta-EYFP) into mouse
      testis. Transgene expression in testis and sperm were analyzed at 20 and 40 days
      after electroporation. MAIN OUTCOME MEASURE(S): Transgene expression in testis
      and epididymal sperm was analyzed by fluorescence microscopy and an excitation
      light source suitable for EYFP. RESULT(S): Phospholipase C zeta-EYFP was
      successfully expressed in epididymal sperm when analyzed 40 days after gene
      transfer and was localized to the head and midpiece regions. CONCLUSION(S): Our
      results provide the first demonstration that in vivo gene transfer can be used to
      study the localization of proteins in mature sperm and that this represents a
      powerful new technique for studying male infertility and gene function in sperm.

PMID- 16616104
TI  - Mutagenesis of putative serine-threonine phosphorylation sites proximal to Arg255
      of human cytochrome P450c17 does not selectively promote its 17,20-lyase
      activity.
AB  - OBJECTIVE: To investigate the role of serine-threonine phosphorylation on the
      activity of human P450c17. DESIGN: In vitro study. SETTING: Academic basic
      research laboratory. PATIENT(S): None. INTERVENTION(S): P450c17 expression
      constructs with a FLAG-tag on either the C-terminus or N-terminus of the protein
      were generated. Human C-terminal FLAG-tagged P450c17 chromosomal DNA was
      subjected to site-directed mutagenesis. Serine 258 and threonine 260 each were
      mutated to alanine and aspartic acid. The mutant P450c17s were expressed in COS-7
      cells, and the enzymatic activities were measured. MAIN OUTCOME MEASURE(S):
      17alpha-Hydroxylase and C(17-20) lyase activities of human P450c17. RESULT(S): C
      terminal FLAG-tagged P450c17 functioned indistinguishably from the wild-type
      P450c17. Mutants S258A, S258D, and T260D had significantly less 17alpha
      hydroxylase and C(17-20) lyase activities than the wild type. CONCLUSION(S):
      Adding an epitope tag to the C-terminus of the P450c17 protein does not interfere
      with its activities and will be a useful tool to isolate human P450c17 protein
      from cultured cells. Phosphorylation of serine 258 but not threonine 260 may act
      as a physiologic regulator of both enzymatic activities through interaction with
      obligatory redox partners.

PMID- 16616105
TI  - Effects of interferon-gamma reverse hypoxia-stimulated extracellular matrix
      expression in human peritoneal and adhesion fibroblasts.
AB  - OBJECTIVE: To determine the response of adhesion and normal peritoneal
      fibroblasts to interferon-gamma (IFN-gamma) under normal and hypoxic conditions.
      DESIGN: Prospective experimental study. SETTING: University medical center.
      PATIENT(S): Primary cultures of fibroblasts established from peritoneal and
      adhesion tissue of the same patients. INTERVENTION(S): Hypoxia and IFN-gamma
      treatment of the primary cultured fibroblasts. MAIN OUTCOME MEASURE(S): Primary
      cultures of fibroblasts were established from peritoneal and adhesion tissues of
      the same patients (n = 5). The expression of extracellular matrix components
      (type I collagen and fibronectin) in adhesion and peritoneal fibroblasts under
      normal (20% O2) and hypoxic (2% O2) conditions was evaluated by multiplex reverse
      transcription polymerase chain reaction analysis. RESULT(S): Adhesion fibroblasts
      (ADF) have increased basal levels of type I collagen as compared with normal
      peritoneal fibroblasts (NF). Interferon-gamma treatment resulted in a dose
      response decrease in type I collagen and fibronectin mRNA levels in both ADF and
      NF. Hypoxia treatment resulted in a time-response increase in type I collagen and
      fibronectin mRNA levels in NF and ADF. Hypoxia had no effect on type I collagen
      and fibronectin mRNA levels in the presence of increasing dose of IFN-gamma in
      both NF and ADF. Interferon-gamma can block the stimulating effects of hypoxia on
      type I collagen expression, supporting the antifibrogenic nature of this
      cytokine. CONCLUSION(S): Understanding the mechanism by which IFN-gamma exerts
      its effect will be important in the utilization of this cytokine as a therapy for
      postoperative adhesion and tissue fibrosis.

PMID- 16616106
TI  - Abnormalities of the long arm of chromosome 21 in 107 patients with hematopoietic
      disorders: a collaborative retrospective study of the Groupe Francais de
      Cytogenetique Hematologique.
AB  - Chromosome 21 is frequently rearranged in hematopoietic malignancies. In order to
      detect new chromosomal aberrations, the Groupe Francais de Cytogenetique
      Hematologique collected a series of 107 patients with various hematologic
      disorders and acquired structural abnormalities of the long arm of chromosome 21.
      The abnormalities were subclassified into 10 groups, according to the location of
      the 21q breakpoint and the type of abnormality. Band 21q22 was implicated in 72
      patients (excluding duplications, triplications, and amplifications). The
      involvement of the RUNX1 gene was confirmed in 10 novel translocations, but the
      gene partners were not identified. Eleven novel translocations rearranging band
      21q22 with bands 1q25, 2p21, 2q37, 3p21, 3p23, 4q31, 6p24 approximately p25,
      6p12, 7p15, 16p11, and 18q21 were detected. Rearrangements of band 21q11 and
      21q21 were detected in six novel translocations with 5p15, 6p21, 15q21, 16p13,
      and 20q11 and with 1p33, 3q27, 5p14, 11q11, and 14q11, respectively.
      Duplications, triplications, amplifications, and isodicentric chromosomes were
      detected in eight, three, eight, and three patients, respectively. The present
      study shows both the wide distribution of the breakpoints on the long arm of
      chromosome 21 in hematopoietic malignancy and the diversity of the chromosomal
      rearrangements and the hematologic disorders involved. The findings invite
      further investigation of the 21q abnormalities to detect their associated
      molecular rearrangements.

PMID- 16616107
TI  - Burkitt t(8;14)(q24;q32) and cryptic deletion in a CLL patient: report of a case
      and review of literature.
AB  - A 53-year-old man diagnosed with chronic lymphocytic leukemia (CLL)-small
      lymphoma following splenectomy was found to have a t(8;14) with an apparent
      cryptic deletion of the MYC gene. This patient's spleen and bone marrow (BM)
      showed that 93% and approximately 70% of the viable cells, respectively, were
      lambda-monoclonal B-cells coexpressing CD5 with CD20, CD19, CD23, CD22, CD38, and
      low FMC-7. The smear showed a marked increase in small, mature lymphoid cells,
      with <2% prolymphocytes. The BM karyotype was 46,XY,t(8;14)(q24;q32),
      18,+mar[3]/46,XY[27] and FISH analysis with an IGH/MYC green-red dual-fusion
      signal probe showed an atypical interphase result of one fusion, two green, and
      one red signal in 70% of the cells. The MYC dual red-green split-apart probe
      showed the expected t(8;14) pattern in 62% of the cells; however, sequential FISH
      on a t(8;14) GTG-metaphase showed the single fusion signal on derivative
      chromosome 8 and only a green signal on der(14) for the IGH/MYC dual-fusion probe
      and a green signal on der(14), red signal on der(8), and fusion signal on the
      normal chromosome 8 for the MYC split-apart probe. Thus, the apparently balanced
      t(8;14) had a cryptic deletion (approximately 1.6 Mb) between the red and the
      green regions flanking the MYC gene in the MYC split-apart probe, 128,585,631
      130,226,339 bp from 8pter. The rarity of t(8;14) in CLL together with a cryptic
      deletion that probably includes the MYC gene in our CLL patient persuaded us to
      explore the clinicopathological role of MYC translocations by comparing disease
      progression in our patient and in other reported CLL cases.

PMID- 16616108
TI  - Linksets of tumor chromosome breakpoints related to survival in ovarian
      adenocarcinoma.
AB  - Biological processes are often accompanied by occurrences of multiple events,
      such as activation of certain cell types, change in prevalence of cell
      subpopulations (such as T cells), changes in concentration of proteins or
      peptides, or breaks in chromosomes. Some co-occurrences of these events are by
      chance, but others may have meaningful relations to the underlying biological
      process. The methodology of linksets is designed to detect the presence of
      potentially meaningful co-occurrences. Due to the complex ways in which linksets
      can determine the observed occurrences of multiple events, some moderately
      powerful computational methods are necessary for statistical estimation. Here,
      linkset models are fitted to data on chromosome breakpoints in ovarian
      adenocarcinomas, in order to answer the question motivating the project that
      collected them--whether there are nonrandom co-occurrences of breakpoints in
      particular chromosome regions, and whether these might be of prognostic
      significance. The results identify breakpoints in 1p1 as associated with early
      mortality when they occur in linksets of breakpoints in 1p3 and any one of 11q1,
      11q2, or 6q2. Conversely, breakpoints in 6p2, 1q3, and 7p1 occur in linksets
      associated with late mortality. This is, to our knowledge, the first
      demonstration of a new method for analyzing patterns of event occurrence in
      biological data.

PMID- 16616109
TI  - DNA copy number alterations and expression of relevant genes in mouse thymic
      lymphomas induced by gamma-irradiation and N-methyl-N-nitrosourea.
AB  - The genetic mechanism for the development and progression of a lymphoma is
      unclear. This study investigated the alterations in the DNA copy number and the
      expression profiles of the genes located in the altered regions in mouse thymic
      lymphomas that were induced by two mutagens, gamma-irradiation and N-methyl-N
      nitrosourea (MNU). Microarray-based comparative genomic hybridization was used to
      precisely delineate the boundaries of the altered region. The copy number gains
      of chromosomes 4 and 5 were observed only in the radiation-induced lymphomas, and
      gains of chromosomes 10 and 14 were observed only in the MNU-induced lymphomas.
      Regional copy number losses in chromosomes 11, 16, and 19 appeared frequently in
      the radiation-induced lymphomas. The cancer-related genes Pten, Ikaros/Znfn1a1,
      Ercc4, and Top3b were located in the minimal deletion regions. In particular, the
      expression levels of the Pten, Top3b, and Ikaros genes were downregulated in both
      lymphoma groups, but the expression level of Ercc4 was downregulated only in the
      MNU group. This study also examined the expression levels of Sparc, Cxcl1, and
      Myc (synonym: c-Myc), which are located in the copy number gained chromosomes.
      Sparc was upregulated specifically in the radiation group, and Cxcl1 in the MNU
      group. c-Myc was upregulated in both groups. There was limited correlation
      between the DNA copy number profiles and the expression of the cancer-related
      genes in mouse lymphomagenesis. The chromosome aberrations and novel expression
      profiles of the cancer-related genes within the altered regions may provide
      important clues to the genetic mechanism for the development of lymphoma.

PMID- 16616110
TI  - BRCA1 and BRCA2 mutations in a South American population.
AB  - A sample of 64 high-risk breast and/or ovarian cancer families from Chile were
      screened for germline mutations in the coding sequences and exon-intron
      boundaries of BRCA1 (MIN no. 113705) and BRCA2 (MIN no. 600185) genes using
      conformation-sensitive gel electrophoresis, and the mutations found were
      confirmed with direct sequencing. Seven families (10.9%) were found to carry
      BRCA1 mutations and three families (4.7%) had BRCA2 mutations. Six different
      pathogenic mutations were detected in BRCA1, four that had been reported
      previously (c.187_188delAG; c.300T-->G, c.3450_3453delCAAG and IVS17-1G-->A) and
      two novel mutations (c.2605_2606delTT and c.4185_4188delCAAG). In BRCA2, we found
      three different pathogenic mutations, two previously described (c.6174delT and
      c.6503_6504delTT) and one novel mutation (c.5667delT). We also identified nine
      variants of unknown significance (five in BRCA1 and four in BRCA2). These
      findings indicate that the Chilean population has a heterogeneous spectrum of
      prevalent BRCA mutations. Given the results obtained in our study, the screening
      of the entire BRCA1 and BRCA2 coding regions is necessary for the molecular
      genetic testing of Chilean high-risk breast/ovarian cancer patients. To our
      knowledge, this is the first genetic study of BRCA gene mutations conducted in
      Chile. The Chilean population has a well-known admixed Amerindian-Caucasian ratio
      and, therefore, our findings are not only important per se, but they constitute
      the basis for improved and more specific genetic counselling, as well as to
      support for preventive campaigns geared toward the Chilean population.

PMID- 16616111
TI  - Diversity of cytogenetic and pathohistologic profiles in glioblastoma.
AB  - We present a small series of patients with primary glioblastoma multiforme (GBM),
      and combine individual genetic data with pathohistologic characteristics and
      clinical outcome. Eighteen patients (12 men, 6 women, median age 51 years) with
      histologically proven GBM underwent surgical debulking followed by radiotherapy.
      Fifteen received concomitant chemotherapy. Histologic typing,
      immunohistochemistry for CD34, karyotypic analysis, and classification of the
      pattern of neovascularization was done in all patients. In 12/18, we performed
      methylation-specific polymerase chain reaction of the MGMT gene (O-6
      methylguanine-DNA methyltransferase). The survival duration of patients spanned 3
      58 months. By classical banding methods, 15/18 patients showed at least one
      aberration characteristic for primary glioblastoma (+7 in 7/18, deletions of 9p
      in 10/18 and -10 or deletions from 10q in 8/18 patients). We could not assess
      whether patients who survived for longer periods showed less complex or fewer
      aberrations than the patients who survived less than one year. Losses of
      6p21(VEGF), 4q27(bFGF), and 12p11 approximately p13 (ING4) were associated with
      the "bizarre" pattern of neoangiogenesis. Methylation of the MGMT promoter was
      found in 3/12 patients. Even in this small series, the main characteristic of GBM
      was its diversity regarding all investigated histologic and genetic
      characteristics. This extreme diversity should be considered in the design of
      targeted therapies in GBM.

PMID- 16616112
TI  - Y chromosome loss and other genomic alterations in hepatocellular carcinoma cell
      lines analyzed by CGH and CGH array.
AB  - Hepatocellular carcinoma (HCC) is one of the most frequently occurring malignant
      tumors worldwide. The incidence of HCC is much higher in males than in females.
      In order to clarify the molecular basis of the male predominance in HCC, we have
      characterized the detailed genomic alterations in 5 hepatitis B virus integrated
      Korean HCC cell lines using G-banding, comparative genomic hybridization (CGH),
      fluorescence in situ hybridization (FISH), PCR, and CGH array. The commonest
      alterations were observed in chromosome 7 and Y, as well as chromosomal regions
      1q, 8q, 4q, and 16q. The most frequent aberration of genomic material was gain of
      1q and loss of chromosome Y. Significant loss of DNA copy number of the cancer
      related genes that are located on chromosome Y was detected by CGH array. By
      investigating the karyotypes of the previously reported 21 male HCC cell lines,
      we found 18 HCC cell lines with Y chromosome loss, indicating that this loss is a
      significant feature of HCC cell lines. We propose that Y chromosome loss in HCC
      cell lines may be responsible for the preponderance of males in HCC and its
      significance may lead to further studies for better understanding of
      carcinogenesis in HCC.

PMID- 16616113
TI  - Deletion of any part of the BCR or ABL gene on the derivative chromosome 9 is a
      poor prognostic marker in chronic myelogenous leukemia.
AB  - To evaluate the prognostic significance of submicroscopic deletions of the ABL or
      BCR gene associated with t(9;22) in chronic myelogenous leukemia (CML), we
      investigated the incidence of an ABL or BCR deletion on derivative chromosome 9
      using fluorescence in situ hybridization (FISH). FISH was performed using the LSI
      BCR/ABL dual-fusion translocation probe on bone marrow cells of 86 patients with
      CML. Of 86 patients, ABL deletion was detected in 13 (15.1%) patients and BCR
      deletion in 8 patients (9.3%). Patients with ABL deletion showed shorter event
      free survival time (EFS) than those without ABL deletion (P = 0.020). Patients
      with BCR deletion showed significantly short overall survival time (OS; P =
      0.039). Patients with ABL and/or BCR deletion (14/86 patients, 16.3%) showed
      significantly short OS and EFS (median OS, 43.0 months; median EFS, 40.0 months),
      compared to the patients without any BCR or ABL gene deletions (median OS, 94.0
      months; median EFS, 90.0 months; P = 0.041 for OS, P = 0.008 for EFS). All the
      patients with BCR deletion, except for one, had a concomitant ABL deletion,
      suggesting that BCR deletion occurs in conjunction with ABL deletion. In patients
      with ABL deletion only, BCR/ABL rearrangement with b2a2 mRNA type tended to be
      more frequent than in patients without any deletion of the two genes (P = 0.073).
      Deletion of any of the BCR or ABL genes on derivative chromosome 9 was associated
      with both short OS and EFS. We conclude that deletion of not only the ABL gene,
      but also of the BCR gene, is a poor prognostic marker that indicates rapid
      disease progression in CML.

PMID- 16616114
TI  - Methylation of RASSF1A and TRAIL pathway-related genes is frequent in childhood
      intracranial ependymomas and benign choroid plexus papilloma.
AB  - Ependymomas (EP) represent the third most frequent type of central nervous system
      (CNS) tumor of childhood, after astrocytomas and medulloblastomas. No prognostic
      biological markers are available, and differentiation from choroid plexus
      papilloma (CPP) is difficult. The present objective was, for a sample of 27
      children with intracranial EP and 7 with CPP, to describe and compare the
      methylation status of 19 genes (with current HUGO symbol, if any): p15INK4a
      (CDKN2B), p16INK4a and p14ARF (both CDKN2A), APC, RB1, RASSF1A (RASSF1), BLU
      (ZMYND10) FHIT, RARB, MGMT, DAPK (DAPK1), ECAD (CDH1), CASP8, TNFRSF10C,
      TNFRSF10D, FLIP (CFLAR), INI1 (SMARCB1), TIMP3, and NF2. Three adult corteses
      were used as a control. We detected a similar percentage of methylated tumors in
      both groups (71% in CPP and 77% in EP). No gene was methylated in that control
      group. RASSF1A was the most frequently methylated gene in both benign tumors
      (66%) and EP (56%). The genes associated with apoptosis were methylated in both
      groups of tumors. The percentages of TRAIL pathway genes (CASP8, TFRSF10C, and
      TFRSF10D) methylated were 30, 9.5, and 36.4%, respectively, in ependymomas and
      50, 50, and 16.7%, respectively, in choroid plexus papillomas. No other gene was
      methylated in the benign tumors, whereas FHIT was methylated in 22%, RARB in
      14.8%, BLU in 13.6%, p16INK4a in 11.1%, TNFRSF10C in 9.5%, and DAPK in 7.4% of
      ependymomas. Although we did not observe a statistical relationship between
      methylation and clinical outcome, the methylation pattern does not appear to be
      randomly distributed in ependymoma and may represent a mechanism of tumor
      development and evolution.

PMID- 16616115
TI  - Translocation (3;8)(q26;q24): a recurrent chromosomal abnormality in
      myelodysplastic syndrome and acute myeloid leukemia.
AB  - We identified a reciprocal translocation between chromosomes 3 and 8, with
      breakpoints at bands 3q26 and 8q24, in five patients with myelodysplastic
      syndrome (MDS) or acute myeloid leukemia (AML). The t(3;8)(q26;q24) was the sole
      cytogenetic aberration in two patients, was associated with trisomy 13 in one
      patient, and occurred with monosomy 7 in two patients. In three patients, the AML
      or MDS developed 36, 52, and 57 months following chemotherapy for soft tissue
      sarcoma, mantle cell lymphoma, and diffuse large B-cell lymphoma, respectively;
      in these three patients, the neoplasms were considered to be therapy-related. All
      five patients displayed marked trilineage dysplasia and variable degrees of
      cytopenias, with marked thrombocytosis noted in one patient and a normal platelet
      count in another patient. All patients were treated with combination
      chemotherapy; at writing, four were still alive and one had died during a follow
      up period ranging from 1 to 16 months. We conclude that the t(3;8)(q26;q24) is a
      recurrent translocation associated with therapy-related MDS/AML or de novo AML,
      and is frequently associated with monosomy 7.

PMID- 16616116
TI  - Three adults with acute lymphoblastic leukemia and dic(7;9)(p11.2;p11).
AB  - We report the cases of three adults with acute lymphoblastic leukemia (ALL) who
      had a dic(7;9)(p11.2;p11) on the diagnostic bone marrow cytogenetic analysis. All
      three were males with B-ALL (aged 25, 38, and 48 years) who at presentation had
      90-100% replacement of marrow with lymphoblasts. One patient died 23 months post
      induction therapy, which was 9 months post allogeneic stem cell transplantation
      (SCT); as of writing, the other two patients were in remission and well, one of
      them at 4 years after SCT and the other at 7.5 years without SCT. To our
      knowledge, these cases are the first reported in adult ALL with dic(7;9) and
      demonstrate a consistent phenotype, with good initial response to therapy but
      variable long-term outcome.

PMID- 16616117
TI  - Studies of complex Ph translocations in cases with chronic myelogenous leukemia
      and one with acute lymphoblastic leukemia.
AB  - The BCR/ABL gene fusion, the hallmark of chronic myelogenous leukemia (CML) is
      generated in 2-10% of patients by a variant Ph translocation involving 9q34,
      22q11.2, and one or more additional genomic regions. The objective of this study
      was the characterization by conventional and molecular cytogenetics of complex
      variant Ph translocations present at diagnosis. FISH studies were performed in 7
      cases using the LSI BCR/ABL ES probe allowing the detection of the fusion BCR/ABL
      gene on the Ph chromosome in all of them and 9q34 deletions in 2 cases. Three
      cryptic complex rearrangements were detected by FISH studies. The third and the
      fourth chromosome regions involved in the 8 complex variant translocations were:
      1q21, 1p36, 5q31, 11q13, 12q13, 12p13, and 20q12. In conclusion, FISH studies
      have been useful in the detection of the BCR/ABL rearrangements and 9q34
      deletions, and to identify complex rearrangements that differ from the ones
      previously established by conventional cytogenetics.

PMID- 16616118
TI  - Numerical investigations of transient heat transfer characteristics and
      vitrification tendencies in ultra-fast cell cooling processes.
AB  - During freezing, cells are often damaged directly or indirectly by ice formation.
      Vitrification is an alternative approach to cryopreservation that avoids ice
      formation. The common method to achieve vitrification is to use relatively high
      concentrations of cryoprotectant agents (CPA) in combination with a relatively
      slow cooling rate. However, high concentrations of CPAs have potentially damaging
      toxic and/or osmotic effects on cells. Therefore, establishing methods to achieve
      vitrification with lower concentrations of CPAs through ultra-fast cooling rates
      would be advantageous in these aspects. These ultra-fast cooling rates can be
      realized by a cooling system with an ultra-high heat transfer coefficient (h)
      between the sample and coolant. The oscillating motion heat pipe (OHP), a novel
      cooling device utilizing the pressure change to excite the oscillation motion of
      the liquid plugs and vapor bubbles, can significantly increase h and may fulfill
      this aim. The current investigation was designed to numerically study the effects
      of different values of h on the transient heat transfer characteristics and
      vitrification tendencies of the cell suspension during the cooling processes in
      an ultra-thin straw (100 microm in diameter). The transient temperature
      distribution, the cooling rate and the volume ratio (x) of the ice quantity to
      the maximum crystallizable ice of the suspension were calculated. From these
      numerical results, it is concluded that the ultra-high h (>10(4) W/m2 K) obtained
      by OHPs could facilitate vitrification by efficiently decreasing x as well as the
      time to pass through the dangerous temperature region where the maximum ice
      formation happens. For comparison, OHPs can decrease both of the parameters to
      less than 20% of those from the widely used open pulled straw methods. Therefore,
      the OHP method will be a promising approach to improving vitrification tendencies
      of CPA solutions and could also decrease the required concentration of CPAs for
      vitrification, both of which are of great importance for the successful
      cryopreservation of cells by vitrification.

PMID- 16616119
TI  - Kruppel acts as a gap gene regulating expression of hunchback and even-skipped in
      the intermediate germ cricket Gryllus bimaculatus.
AB  - In Drosophila, a long germ insect, segmentation occurs simultaneously across the
      entire body. In contrast, in short and intermediate germ insects, the anterior
      segments are specified during the blastoderm stage, while the remaining posterior
      segments are specified during later stages. In Drosophila embryos, the
      transcriptional factors coded by gap genes, such as Kruppel, diffuse in the
      syncytial environment and regulate the expression of other gap, pair-rule, and
      Hox genes. To understand the segmentation mechanisms in short and intermediate
      germ insects, we investigated the role of Kr ortholog (Gb'Kr) in the development
      of the intermediate germ insect Gryllus bimaculatus. We found that Gb'Kr is
      expressed in a gap pattern in the prospective thoracic region after
      cellularization of the embryo. To determine the function of Gb'Kr in
      segmentation, we analyzed knockdown phenotypes using RNA interference (RNAi).
      Gb'Kr RNAi depletion resulted in a gap phenotype in which the posterior of the
      first thoracic through seventh abdominal segments were deleted. Analysis of the
      expression patterns of Hox genes in Gb'Kr RNAi embryos indicated that regulatory
      relationships between Hox genes and Kr in Gryllus differ from those in
      Oncopeltus, another intermediate germ insect. Furthermore, we found that Gb'Kr
      regulates expression minimally of hunchback and even-skipped, directly or
      indirectly, in the prospective thoracic region. Our findings suggest that Gb'Kr
      is a gap gene that acts in the cellular environment and is required for
      segmentation in the thoracic and abdominal regions through the regulation of gap
      and pair-rule gene expression.

PMID- 16616121
TI  - Novel regulators revealed by profiling Drosophila testis stem cells within their
      niche.
AB  - Stem cells are defined by the fact that they both self-renew, producing
      additional stem cells, and generate lineal descendants that differentiate into
      distinct functional cell types. In Drosophila, a small germline stem cell
      population is influenced by a complex microenvironment, the stem cell niche,
      which itself includes a somatic stem cell population. While stem cells are
      unique, their immediate descendants retain considerable stem cell character as
      they mitotically amplify prior to differentiation and can be induced to de
      differentiate into stem cells. Despite their importance, very few genes are known
      that are expressed in the stem cells or their early amplifying daughters. We
      present here whole-genome microarray expression analysis of testes specifically
      enriched for stem cells, their amplifying daughters, and their niche. These
      studies have identified a number of loci with highly specific stem cell
      expression and provide candidate downstream targets of Jak/Stat self-renewal
      signaling. Furthermore, functional analysis for two genes predicted to be
      enriched has enabled us to define novel regulators of the germline lineage. The
      gene list generated in this study thus provides a potent resource for the
      investigation of stem cell identity and regulation from functional as well as
      evolutionary perspectives.

PMID- 16616120
TI  - Post-implantation mouse conceptuses produce paracrine signals that regulate the
      uterine endometrium undergoing decidualization.
AB  - The uterus undergoes a series of dramatic changes in response to an implanting
      conceptus that, in some mammalian species, includes differentiation of the
      endometrial stroma into decidual tissue. This process, called decidualization,
      can be induced artificially in rodents indicating that the conceptus may not be
      essential for a proper maternal response in early pregnancy. In order to test
      this hypothesis, we determined if and how the conceptus affects uterine gene
      expression. We identified 5 genes (Angpt1, Angpt2, Dtprp, G1p2 and Prlpa) whose
      steady-state levels in the uterus undergoing decidualization depends on the
      presence of a conceptus. In situ hybridization revealed region-specific effects
      which suggested that various components of the conceptus and more than one signal
      from the conceptus are likely responsible for altering decidual cell function.
      Using cell culture models we found that trophoblast giant cells secrete a type I
      interferon-like molecule which can induce G1p2 expression in endometrial stromal
      cells. Finally, decidual Prlpa expression was reduced in the uterus adjacent to
      Hand1- and Ets2-deficient embryos, suggesting that normal trophoblast giant cells
      in the placenta are required for the conceptus-dependent effects on Prlpa
      expression in the mesometrial decidua. Overall, these results provide support for
      the hypothesis that molecular signals from the mouse conceptus have local effects
      on uterine gene expression during decidualization.

PMID- 16616122
TI  - The effect of denture factors on masticatory performance part III. The location
      of food platforms. 1965.

PMID- 16616123
TI  - Prosthetic rehabilitation of a mandibular gunshot defect with an implant
      supported fixed partial denture: a clinical report.
AB  - This report describes the clinical evaluation of a patient with a mandibular
      gunshot defect and the prosthodontic treatment with an implant-supported screw
      retained fixed partial denture. Treatment included cemented crowns for 2
      maxillary implants and an implant-supported screw-retained fixed partial denture
      supported by 8 mandibular implants. Despite the implant malposition limitations,
      the esthetic and functional demands of the patient were fullfilled.

PMID- 16616124
TI  - Stent fabrication for graft immobilization following wide surgical excision of
      myofibroblastic sarcoma of the buccal mucosa: a clinical report.
AB  - Sarcomas of the head and neck are rare tumors derived from cells of mesenchymal
      origin. This article briefly discusses the epidemiology, etiology, and
      classification of head and neck sarcomas. Emphasis is placed on myofibrosarcoma,
      a malignant tumor of the myofibroblasts. Histologic criteria, prognostic factors,
      and the multidisciplinary management of these tumors are reviewed. A situation of
      a surgically excised myofibrosarcoma of the buccal mucosa is reported. In this
      patient, a stent was fabricated to stabilize a split-thickness skin graft used
      for the buccal mucosa reconstruction.

PMID- 16616125
TI  - Effect of bleaching agents on the microhardness of tooth-colored restorative
      materials.
AB  - STATEMENT OF PROBLEM: There is no consensus concerning the effect of bleaching
      gels on microhardness of restorative materials. Information about the effect of
      whitening strips on microhardness of restorative materials is also limited.
      PURPOSE: The purpose of this study was to evaluate the effect of a bleaching gel
      and a whitening strip on the microhardness of 3 tooth-colored restorative
      materials. MATERIAL AND METHODS: Forty cylindrical specimens (6 x 2 mm) of each
      restorative material, including a nanohybrid composite resin (Grandio), a
      polyacid-modified composite resin (Dyract eXtra), and a glass-ionomer cement
      (Ionofil Molar AC), were prepared and stored in distilled water at 37 degrees C
      for 24 hours. The specimens were then polished using medium, fine, and superfine
      polishing disks and stored in 37 degrees C distilled water for 7 days. Specimens
      were divided into 4 groups (n=10). One group was selected for baseline Vickers
      hardness measurements (load 100 g, dwell time 20 seconds) of the top surfaces.
      The other 3 groups were treated for 21 days with 1 of the following: distilled
      water (control), bleaching gel (10% carbamide peroxide), or whitening strip (14%
      hydrogen peroxide). The top surfaces of the treated specimens were also subjected
      to the same hardness testing performed for the baseline specimens. Data were
      analyzed with 2-way analysis of variance and Tukey Honestly Significant
      Difference tests (alpha=.05). RESULTS: There were no significant differences in
      microhardness between the test groups of each restorative material. However,
      significant differences in microhardness were observed among restorative
      materials. For all test groups, composite resin showed the highest hardness
      values, whereas glass-ionomer cement presented the lowest (P<.05). CONCLUSION:
      The bleaching products used in this study did not adversely affect the
      microhardness of the restorative materials.

PMID- 16616126
TI  - Influence of remaining coronal tooth structure location on the fracture
      resistance of restored endodontically treated anterior teeth.
AB  - STATEMENT OF PROBLEM: A restored endodontically treated tooth is less likely to
      fracture when there is axial tooth structure between the core base and
      preparation finish line. However, an accurate prognosis requires knowing whether
      fracture resistance depends on a complete circumferential distribution of tooth
      structure or tooth structure in a specific location related to the applied force.
      PURPOSE: This in vitro study investigated the fracture resistance of restored
      endodontically treated teeth when residual axial tooth structure was limited to
      one half the circumference of the crown preparation. MATERIAL AND METHODS: Fifty
      extracted maxillary anterior teeth were sectioned 18 mm from their apices,
      endodontically treated, and divided into 5 groups of 10 teeth each. Four groups
      were prepared with full shoulder crown preparations having axial wall heights of
      2 mm around the preparation circumferences. In 3 of the groups with axial tooth
      structure, one half of the axial tooth structure was removed, palatally,
      labially, or proximally, and groups were identified according to the site of
      retained coronal tooth structure. For the fifth group, all axial tooth structure
      was removed to the level of the preparation shoulder. Thus, in 1 group the axial
      walls were circumferential, 360 degrees around the preparations (Complete group),
      in 3 groups the axial walls were continuous for 180 degrees (Palatal, Labial, and
      Proximal groups), and the last group had no retained coronal tooth structure
      incisal to the finish line (Level group). All 50 prepared teeth were then
      restored with quartz fiber posts (Bisco), composite resin (Bisco) cores, and
      metal crowns. A universal testing machine compressively loaded the tooth
      specimens from the palatal at a crosshead speed of 0.5 cm/min at an angle of 135
      degrees to the long axis of teeth until failure occurred. A survival analysis was
      conducted using a log-rank test followed by Holm-Sidak pairwise tests (alpha=.05)
      to detect significant differences in median failure load between groups. The mode
      of failure was determined by visual inspection of all specimens. RESULTS: The
      median failure load (P<.001) was 607 N, 782 N, 358 N, 375 N, and 172 N for the
      Complete, Palatal, Labial, Proximal, and Level groups, respectively. The
      predominant mode of failure was an oblique palatal to facial root fracture for
      the groups with remaining coronal tooth structure. In the Level group, post
      debonding was the predominant mode of failure. CONCLUSION: For restored
      endodontically treated teeth that do not have complete circumferential tooth
      structure between the core and preparation finish line, the location of the
      remaining coronal tooth structure may affect their fracture resistance.

PMID- 16616127
TI  - Effect of dentin bonding and ferrule preparation on the fracture strength of
      crowned teeth restored with dowels and amalgam cores.
AB  - STATEMENT OF PROBLEM: It is necessary to obtain an adequate bond at the
      core/dentin junction where the majority of failures occur. The effect of recently
      developed dentin bonding agents on the fracture resistance of endodontically
      treated teeth at the amalgam core/dentin junction is unclear. PURPOSE: The
      purpose of this study was to evaluate the effects of 2 dentin bonding agents and
      a ferrule preparation on the fracture resistance of crowned mandibular premolars
      incorporating prefabricated dowel and silver amalgam cores. MATERIAL AND METHODS:
      Sixty extracted mandibular second premolars were divided into 6 groups of 10
      each. The coronal portion of each tooth was removed at the cemento-enamel
      junction (CEJ) in the first 3 groups. In the other groups, teeth were sectioned 1
      mm above the CEJ to create a ferrule. After root canal preparations,
      prefabricated dowels (ParaPost) were placed. The first group served as a control
      and was tested without application of bonding agents and without incorporation of
      a ferrule design. In the second and third groups, respectively, an
      autopolymerizing adhesive (Superbond D-Liner) and a dual-polymerizing adhesive
      (Panavia F) were applied to tooth surfaces before restorative procedures. For the
      fourth (ferrule) group, no bonding agent was applied, but a 1-mm ferrule
      preparation was used. In the fifth (ferrule+D-Liner) and sixth (ferrule+Panavia
      F) groups, respectively, autopolymerizing and dual-polymerizing bonding agents
      were used in conjunction with the ferrule preparation. After amalgam core
      fabrication, Ni-Cr full cast crowns for each group were prepared and cemented.
      All specimens were stored in water for 1 week and thermal cycled 1000 times
      between 5 degrees and 55 degrees C. A compressive shear load was applied at an
      angle of 135 degrees to the crown, and the maximum load at fracture (N) was
      recorded. The data were analyzed with 1-way ANOVA and Tukey Honestly Significant
      Difference tests (alpha=.05). RESULTS: Significantly higher fracture strength
      values were demonstrated for the ferrule+Panavia F (652.5 N), ferrule+D-liner
      (649.1 N) and ferrule (592.4 N) groups, respectively, than for the other groups.
      The next highest fracture strength values were found for the D-Liner (485.0 N)
      and Panavia F (486.3 N) groups. The control group (376.6 N) demonstrated the
      lowest fracture strength in all test groups (P<.001). CONCLUSION: A ferrule
      preparation or a bonding agent designed for silver amalgam core-dentin bonding
      can each increase the fracture strength for teeth receiving cast crowns after
      endodontic therapy and dowel and amalgam core restorations.

PMID- 16616128
TI  - In vitro evaluation of push-out bond strengths of various luting agents to tooth
      colored posts.
AB  - STATEMENT OF PROBLEM: Different compositions of tooth-colored posts may influence
      the bonding capacity of various luting agents to these posts. An appropriate
      understanding of these interactions is presently unavailable. PURPOSE: This study
      initially evaluated the effects of various pretreatment procedures on bond
      strengths to zirconium-oxide posts using a phosphate-methacrylate resin luting
      agent. Following that investigation, the bond strengths of various luting agents
      to tribochemically coated glass-fiber-reinforced composite (FRC) resin and
      zirconium-oxide posts were investigated. MATERIAL AND METHODS: Two hundred
      zirconium-oxide posts (CosmoPost) divided into 10 groups (n=20) were luted into
      artificial post spaces prepared with drills provided by the manufacturer. In 4
      groups the posts were luted with phosphate-methacrylate resin agent (Panavia F)
      after receiving one of the following pretreatment procedures: no treatment
      (control); airborne-particle abrasion; silica coating and silanization with an
      intraoral airborne-particle-abrasion device (CoJet); or silica coating and
      silanization with a laboratory airborne-particle-abrasion device in combination
      with airborne-particle abrasion (Rocatec). The other zirconium-oxide posts in the
      6 remaining groups were silica coated (CoJet), silanated, and luted with 1 of 6
      different luting agents (Multilink, Variolink, PermaFlo DC, RelyX Unicem,
      Clearfil Core, and Ketac Cem). Additionally, 60 FRC posts (FRC Postec) were
      silica coated (CoJet), silanated, and luted with 1 of the 6 resin luting agents
      (Panavia F, Multilink, Variolink, PermaFlo DC, RelyX, and Clearfil Core). Push
      out tests were performed to evaluate the bond strengths between luting agents and
      posts. Qualitative scanning electron microscopy (SEM) analyses were performed to
      evaluate the effects of the pretreatment procedures on the surface of the
      zirconium-oxide posts. Data were analyzed using analysis of variance (ANOVA)
      followed by the post hoc Tukey B test (alpha=.05). RESULTS: Bond strengths to the
      posts were significantly affected by the type of luting agent and the type of
      post (P<.001; 2-way ANOVA). Bond strengths of all luting agents to the FRC posts
      were significantly higher than to the zirconium-oxide posts (P<.01), except for
      Multilink and PermaFlo DC, which demonstrated higher bond strength values to the
      zirconium-oxide posts (P<.001). Pretreatment procedures significantly increased
      the bond strength of Panavia F to the zirconium-oxide posts (P<.05). SEM analyses
      revealed distinctive irregularities on the surface of the pretreated zirconium
      oxide posts compared to the untreated posts. CONCLUSION: Bond strengths of luting
      agents to tooth-colored posts are significantly affected by the type of luting
      agent and the type of post. All investigated pretreatment procedures of zirconium
      oxide posts significantly increased the bond strength of Panavia F.

PMID- 16616129
TI  - Clinical evaluation of pulpless teeth restored with conventionally cemented
      zirconia posts: a pilot study.
AB  - STATEMENT OF PROBLEM: Adhesive resin cements are commonly used to lute all
      ceramic posts despite limited scientific data on the clinical effectiveness of
      using bonding agents within prepared root canals. PURPOSE: The purpose of this
      study was to retrospectively evaluate the clinical performance of conventionally
      cemented zirconia posts. Loss of retention, fracture of posts, and fracture of
      teeth were evaluated. MATERIAL AND METHODS: Thirty pulpless teeth in 22 patients
      were treated with zirconia posts. With the exception of 3 situations in which
      posts were inserted directly and the access openings were closed with composite
      resin, teeth were restored with indirectly fabricated post-and-core foundations
      made from zirconia posts (Cerapost or Cosmopost) combined with heat-pressed
      ceramic cores (IPS Empress Cosmo) and ceramic crowns (IPS Empress II).
      Restorations (posts and crowns) were cemented with glass-ionomer cement
      (KetacCem) or resin-modified glass-ionomer cement (ProTec Cem) and reevaluated,
      retrospectively, for failures such as loss of retention or fractures. Data were
      reported using descriptive statistics. RESULTS: The mean observation period was
      29 months (range 8-44 months). No loss of retention or fracture of any
      restoration was observed. CONCLUSION: Although this study involved a relatively
      short observation period, there were no signs of failure of conventionally
      cemented zirconia posts with ceramic crowns.

PMID- 16616130
TI  - Load-fatigue performance of gold crowns luted with resin cements.
AB  - STATEMENT OF PROBLEM: Resin cements have gained popularity over the past few
      years because of their improved physical properties. There is a need to test
      these cements under fatigue loading, as there is growing recognition that fatigue
      testing is more clinically relevant than traditional monotonic static tests.
      PURPOSE: This study investigated the load-fatigue performance of complete gold
      crowns cemented with 4 types of resin cement. MATERIAL AND METHODS: Four resin
      cements (C & B Opaque [CBO], Calibra Esthetic [CE], RelyX Unicem [RU], and
      Panavia F [PF]) and a control, zinc phosphate cement (HY-Bond [HBZPC]) were
      tested. Fifty human maxillary premolars were prepared to an occluso-cervical
      dimension of 4 mm and a convergence angle of 20 degrees. Complete gold crowns
      were cast (Strator 3) and cemented with 1 of the 5 cements (n=10). A fatigue load
      of 73.5 N was applied at an angle of 135 degrees to the long axis of each tooth
      crown specimen. Preliminary failure was defined as the propagation of a crack in
      or around the crown luting cement layer. The number of cycles to preliminary
      failure and the cement failure location were determined. Significant differences
      in cycles to preliminary failure were assessed by the nonparametric Kruskal
      Wallis test, with follow-up Mann-Whitney tests (alpha=.05). RESULTS: Group CE had
      the highest rank of cycles to preliminary failure, while HBZPC had the lowest
      cycles to preliminary failure. Group CE had a significantly higher failure cycle
      count compared to PF (P=.016), RU (P=.001), and HBZPC (P<.001), but was not
      significantly different from CBO (P=.112). There was no significant difference in
      the failure cycle count between RU and HBZPC (P=.070). CONCLUSION: Not all tested
      resin cements had a superior fatigue life when compared with zinc phosphate
      cement. Of the 4 resin cement groups, Groups CE, CBO, and PF were significantly
      superior to HBZPC.

PMID- 16616131
TI  - A clinical investigation of the fit of removable partial dental prosthesis clasp
      assemblies.
AB  - STATEMENT OF PROBLEM: Removable partial denture frameworks are complex castings
      fabricated from high-shrinkage alloys. This may result in difficulty in achieving
      accurate fit. PURPOSE: The purpose of this study was to evaluate which
      component(s) of the clasp assembly contact the abutment tooth clinically.
      MATERIAL AND METHODS: New and existing frameworks with at least 1 conventional
      prepared occlusal rest were evaluated for fit. The spacing between the bottom of
      each of the rests of the 50 clasp assemblies and the corresponding rest seat were
      recorded with vinyl polysiloxane. The fit of each rest was determined with the
      use of a dial caliper by measuring, in micrometers, the thickness of the record
      between the rest and the bottom of the rest seat. The Kennedy classification was
      also recorded. A 2-sample t test was used to evaluate the difference in fit
      between tooth-tissue supported and tooth-supported designs (alpha=.05). RESULTS:
      The average space between the rest and prepared rest seat was 193 +/- 203 microm,
      with a range of 0 to 828 mum. Twenty tooth-tissue frameworks had an average space
      of 136 +/- 160 microm and 30 tooth-supported frameworks had an average space of
      230 +/- 222 microm. The 2-sample t test showed no significant difference for fit
      between tooth-tissue supported and tooth-supported frameworks (P=.1081). Twenty
      four percent of rests had contact in the prepared rest seat. CONCLUSION: The
      majority of rests evaluated did not contact the intended surfaces.

PMID- 16616132
TI  - Digital imaging in the fabrication of ocular prostheses.
AB  - Several ocular and orbital disorders require surgical intervention that may
      result in ocular defects. The associated psychological effect of these defects on
      the patient requires immediate management and rehabilitation intervention by a
      team of specialists. The role of the maxillofacial prosthodontist in fabricating
      an ocular prosthesis with acceptable esthetics to restore facial symmetry and
      normal appearance for the anophthalmic patient becomes essential. This article
      presents a technique for fabricating ocular prostheses using the advantages of
      digital photography.

PMID- 16616133
TI  - Repositioning implant replicas after soldering a fixed complete denture
      framework.

PMID- 16616134
TI  - Evaluating closest speaking space with Spanish terms.

PMID- 16616135
TI  - Framework for gender differences in human and animal toxicology.
AB  - Differences in exposure, anatomy, physiology, biochemistry, and behavior between
      males and females are a dominant theme in biology, transcending the plant and
      animal kingdoms. Yet differences due to sex and gender have not received adequate
      attention in human or animal toxicology nor always in epidemiology.
      Generalizations are often made about species' responses to xenobiotics, without
      data or consideration of female/male differences. Despite the leading role that
      pharmacology and drug development play in elucidating toxicokinetics, gender
      studies are relatively recent. Phenomenologic or clinical observations of sex
      differences often go unexplored, but pharmaceutical companies recognize the
      importance of enhanced understanding of toxicokinetics and toxicodynamics and
      emphasize the value of translational or integrational research--bringing
      laboratory findings to bedside applications and bedside questions to laboratory
      study. However, for many years Food and Drug Administration guidelines
      specifically precluded participation of females in many drug studies. Many
      occupational epidemiology studies, on which much of our understanding of toxic
      effects is based, begin by excluding women and minorities. Sex differentiation
      begins in the embryo under genetic and hormonal control. Changes affecting
      exposure, susceptibility, risk, and health continue throughout life. This paper
      provides a framework for analyzing the level(s) at which gender differences
      arise. The framework addresses exposure, toxicokinetics, toxicodynamics, and
      modulating influences. Men and women differ in many aspects of vulnerability to
      xenobiotics and other stressors, beginning with their opportunities for exposure.
      Toxicokinetic differences mainly involve metabolism, with few differences in
      absorption yet demonstrated. In addition, lifestyle, psychosocial, and hormonal
      factors modify the kinetics and responsiveness. Some phenomena fit the Classic
      Sex Hormone Paradigm in which castration (with and without hormone replacement)
      and administration of the opposite sex hormone demonstrate the primary regulatory
      role of sex hormones. Many phenomena, however, differ between males and females
      without showing a clear-cut relationship with the sex hormones. Since every cell
      both has a sex chromosome (X or Y) and is exposed to hormones, elegant techniques
      are just beginning to tease apart genetic from hormonal influences. Wherever
      possible, studies should use balanced gender and gender x age designs and should
      analyze data by sex and interactions, rather than simply adjusting for
      (discarding) gender. Power should be adequate, or lack of power (if inevitable)
      should be clearly stated.

PMID- 16616136
TI  - Iron and copper accumulation in the brain of coxsackievirus-infected mice exposed
      to cadmium.
AB  - Cadmium (Cd) is a potentially toxic metal widely distributed in the environment
      and known to cause adverse health effects in humans. During coxsackievirus
      infection, the concentrations of essential and nonessential trace elements (e.g.,
      iron (Fe), copper (Cu), and Cd) change in different target organs of the
      infection. Fe and Cu are recognized cofactors in host defence reactions, and Fe
      is known to be associated with certain pathological conditions of the brain.
      However, whether nonessential trace elements could influence the balance of
      essential trace elements in the brain is unknown. In this study the brain Fe, Cu,
      and Cd contents were measured through inductively coupled plasma mass
      spectrometry and their distributions determined by nuclear microscopy in the
      early phase (day 3) of coxsackievirus B3 (CB3) infection in nonexposed and in Cd
      exposed female Balb/c mice. In CB3 infection the brain is a well-known target
      that has not been studied with regard to trace element balance. The brain
      concentration of Cu compared with that of noninfected control mice was increased
      by 9% (P < 0.05) in infected mice not exposed to Cd and by 10% (not significant)
      in infected Cd-exposed mice. A similar response was seen for Fe, which in
      infected Cd-exposed mice, compared to noninfected control mice, tended to
      increase by 16%. Cu showed an even tissue distribution, whereas Fe was
      distributed in focal deposits. Changes in Cd concentration in the brain of
      infected mice were less consistent but evenly distributed. Further studies are
      needed to define whether the accumulation and distribution of trace elements in
      the brain have an impact on brain function.

PMID- 16616137
TI  - Leishmania donovani: effect of verapamil on in vitro susceptibility of
      promastigote and amastigote stages of Indian clinical isolates to sodium
      stibogluconate.
AB  - Although pentavalent antimonials are the first-line drug for treatment of
      visceral leishmaniasis all over the world, yet, in India, increasing number of
      patients are being reported to be unresponsive to sodium stibogluconate.
      Verapamil, a calcium channel blocker, affects drug uptake by preventing its
      efflux and thereby accumulation within the cell. In the present study, effect of
      verapamil on in vitro susceptibility of both promastigote and amastigote stages
      of 15 clinical isolates and standard strain of Leishmania donovani to sodium
      stibogluconate was evaluated by detection of acid phosphatase. Amastigotes were
      found more susceptible to sodium stibogluconate than the promastigotes (p<0.05)
      and in the presence of verapamil, IC(50) value of sodium stibogluconate was
      reduced only for those isolates, which had a higher IC(50). Verapamil alone did
      not have any effect on the parasites. The results indicate that amastigotes are
      more susceptible to sodium stibogluconate than promastigotes and verapamil can
      reverse the in vitro drug resistance of L. donovani clinical isolates to sodium
      stibogluconate.

PMID- 16616138
TI  - The catalytic power of enzymes: conformational selection or transition state
      stabilization?
AB  - The mechanism by which enzymes produce enormous rate enhancements in the
      reactions they catalyze remains unknown. Two viewpoints, selection of ground
      state conformations and stabilization of the transition state, are present in the
      literature in apparent opposition. To provide more insight into current
      discussion about enzyme efficiency, a two-state model of enzyme catalysis was
      developed. The model was designed to include both the pre-chemical (ground state
      conformations) and the chemical (transition state) components of the process for
      the substrate both in water and in the enzyme. Although the model is of general
      applicability, the chorismate to prephenate reaction catalyzed by chorismate
      mutase was chosen for illustrative purposes. The resulting kinetic equations show
      that the catalytic power of enzymes, quantified as the k(cat)/k(uncat) ratio, is
      the product of two terms: one including the equilibrium constants for the
      substrate conformational states and the other including the rate constants for
      the uncatalyzed and catalyzed chemical reactions. The model shows that these
      components are not mutually exclusive and can be simultaneously present in an
      enzymic system, being their relative contribution a property of the enzyme. The
      developed mathematical expressions reveal that the conformational and reaction
      components of the process perform differently for the translation of molecular
      efficiency (changes in energy levels) into observed enzymic efficiency (changes
      in k(cat)), being, in general, more productive the component involving the
      transition state.

PMID- 16616139
TI  - Characterization of human D-amino acid oxidase.
AB  - D-Amino acid oxidase (DAAO) has been proposed to be involved in the oxidation of
      D-serine, an allosteric activator of the NMDA-type glutamate receptor in the
      brain, and to be associated with the onset of schizophrenia. The recombinant
      human DAAO was expressed in Escherichia coli and was isolated as an active
      homodimeric flavoenzyme. It shows the properties of the dehydrogenase-oxidase
      class of flavoproteins, possesses a low kinetic efficiency, and follows a ternary
      complex (sequential) kinetic mechanism. In contrast to the other known DAAOs, the
      human enzyme is a stable homodimer even in the apoprotein form and weakly binds
      the cofactor in the free form.

PMID- 16616140
TI  - Stable RNA interference of host thrombospondin-1 blocks Trypanosoma cruzi
      infection.
AB  - Interactions between Trypanosoma cruzi and the extracellular matrix play an
      important role in cellular invasion. Here we show that T. cruzi increases the
      levels of thrombospondin-1 (TSP-1) expression in host cells during early
      infection. Stable RNA interference of host cell TSP-1 knocks down the levels of
      TSP-1 transcripts and protein expression in mammalian cells causing inhibition of
      T. cruzi infection. Addition of TSP-1 to these cells restores infection. Thus,
      host TSP-1, regulated by the parasite, plays a crucial role in early infection.
      This is the first report showing that a human parasite modulates TSP-1 expression
      to facilitate infection.

PMID- 16616141
TI  - Evidence that low doses of Taxol enhance the functional transactivatory
      properties of p53 on p21 waf promoter in MCF-7 breast cancer cells.
AB  - In the present study, we evidence how in breast cancer cells low doses of Taxol
      for 18 h determined the upregulation of p53 and p21 waf expression concomitantly
      with a decrease of the anti-apoptotic Bcl-2. P53 and its gene product, the mdm2
      protein, in treated cells exhibits a prevalent nuclear compartmentalization, thus
      potentiating p53 transactivatory properties. Indeed, the most important finding
      of this study consists with the evidence that Taxol at lower concentrations is
      able to produce the activation of p21 promoter via p53. Prolonged exposure of MCF
      7 cells to Taxol (48 h) resulted in an increased co-association between p21 and
      PCNA compared to control and this well fits with the simultaneous block of cell
      cycle into the G2/M phase.

PMID- 16616142
TI  - Expression of the Arabidopsis high-affinity hexose transporter STP13 correlates
      with programmed cell death.
AB  - We report the biochemical characterization in Xenopus oocytes of the Arabidopsis
      thaliana membrane protein, STP13, as a high affinity, hexose-specific H(+)
      symporter. Studies with kinase activators suggest that it is negatively regulated
      by phosphorylation. STP13 promoter GFP reporter lines show GFP expression only in
      the vascular tissue in emerging petals under non-stressed conditions.
      Quantitative PCR and the pSTP13-GFP plants show induction of STP13 in programmed
      cell death (PCD) obtained by treatments with the fungal toxin fumonisin B1 and
      the pathogen Pseudomonas syringae. A role for STP13 in PCD is supported by
      microarray data from e.g. plants undergoing senescence and a strong correlation
      between STP13 transcripts and the PCD phenotype in different accelerated cell
      death (acd11) mutants.

PMID- 16616143
TI  - Casein kinase I epsilon associates with and phosphorylates the tight junction
      protein occludin.
AB  - Occludin is an integral-membrane protein that contributes to tight junction
      function. We have identified casein kinase I epsilon (CKI epsilon) as a binding
      partner for the C-terminal cytoplasmic domain of occludin by yeast two-hybrid
      screening. CKI epsilon phosphorylated occludin and co-localised and co
      immunoprecipitated with occludin from human endothelial cells. Amino acids 265
      318 of occludin were sufficient for CKI epsilon binding and phosphorylation.
      Deletion of the C-terminal 48 amino acids of occludin increased CKI epsilon
      binding and phosphorylation, suggesting that this region inhibits CKI epsilon
      binding. These data identify CKI epsilon as a novel occludin kinase that may be
      important for the regulation of occludin.

PMID- 16616144
TI  - Using Caenorhabditis elegans for functional analysis of genes of parasitic
      nematodes.
AB  - Information on the functional genomics of Caenorhabditis elegans has increased
      significantly in the last few years with the development of RNA interference. In
      parasitic nematodes, RNA interference has shown some success in gene knockdown
      but optimisation of this technique will be required before it can be adopted as a
      reliable functional genomics tool. Comparative studies in C. elegans remain an
      appropriate alternative for studying the function and regulation of some parasite
      genes and will be extremely useful for fully exploiting the increasing parasite
      genome sequence data becoming available.

PMID- 16616145
TI  - Human cerebral malaria and the blood-brain barrier.
AB  - Malaria represents a continuing and major global health challenge and our
      understanding of how the Plasmodium parasite causes severe disease and death
      remains poor. One serious complication of the infection is cerebral malaria, a
      clinically complex syndrome of coma and potentially reversible encephalopathy,
      associated with a high mortality rate and increasingly recognised long-term
      sequelae in survivors. Research into the pathophysiology of cerebral malaria,
      using a combination of clinical and pathological studies, animal models and in
      vitro cell culture work, has focussed attention on the blood-brain barrier (BBB).
      This represents the key interface between the brain parenchyma and the parasite,
      which develops within an infected red cell but remains inside the vascular space.
      Studies of BBB function in cerebral malaria have provided some evidence for
      parasite-induced changes secondary to sequestration of parasitised red blood
      cells and host leukocytes within the cerebral microvasculature, such as
      redistribution of endothelial cell intercellular junction proteins and
      intracellular signaling. However, the evidence for a generalised increase in BBB
      permeability, leading to cerebral oedema, is conflicting. As well as direct cell
      adhesion-dependent effects, local adhesion-independent effects may activate and
      damage cerebral endothelial cells and perivascular cells, such as decreased blood
      flow, hypoxia or the effects of parasite toxins such as pigment. Finally, a
      number of systemic mechanisms could influence the BBB during malaria, such as the
      metabolic and inflammatory complications of severe disease acting 'at a
      distance'. This review will summarise evidence for these mechanisms from human
      studies of cerebral malaria and discuss the possible role for BBB dysfunction in
      this complex and challenging disease.

PMID- 16616146
TI  - Effects of homocysteine on the levels of caveolin-1 and eNOS in caveolae of human
      coronary artery endothelial cells.
AB  - One aspect of homocysteine (Hcy) action is the impairment of endothelial cell
      function due to an impairment of endothelial nitric oxide (NO) production. The
      activity of the endothelial isoform of NO synthase (eNOS) is regulated by its
      interaction with caveolin-1 (Cav-1). The aim of this study was to determine
      whether Hcy may alter the levels of Cav-1 and eNOS in endothelial caveolae. We
      isolated caveolae-enriched membrane fractions from Hcy-treated human coronary
      artery endothelial cells. We found that treatment with 500 microM Hcy for 6h
      significantly reduced the levels of Cav-1 and eNOS in caveolae compared to
      untreated control by 47+/-7% and by 38+/-14%, respectively. Similarly, long-term
      incubation (96h) of HCAEC with 100 microM Hcy led to a comparable effect. The
      decreased Cav-1 abundance in endothelial caveolae in response to Hcy resulted
      from a decrease in Cav-1 expression at the transcriptional level. The reduced
      levels of eNOS in caveolae were caused by a translocation of eNOS from the
      caveolar fractions to noncaveolar fractions. The effects of Hcy were associated
      with an impairment of stimulated release of NO. These results suggest that Hcy
      induced impairment of NO production through a modulation of Cav-1 expression
      associated with a loss of eNOS in caveolae.

PMID- 16616148
TI  - Pyogenic arthritis of the facet joints: a growing problem for patients, a growing
      concern for clinicians.

PMID- 16616147
TI  - Eicosapentaenoic acid reduces the progression of carotid intima-media thickness
      in patients with type 2 diabetes.
AB  - To investigate the effect of highly purified eicosapentaenoic acid (EPA) on the
      progression of diabetic macroangiopathy, we performed an open-label randomized
      prospective trial. A total of 81 Japanese type 2 diabetes were randomly assigned
      to the EPA (1800 mg/day) treated group or the control group. Carotid intima-media
      thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were evaluated
      before and after treatment in both groups. Sixty patients (EPA group, n=30;
      control group, n=30) completed this study. During the study period of 2.1+/-0.2
      years, the mean IMT and max IMT of the EPA treated group showed a significant
      annual decrease compared with that of the control group (mean IMT, -0.029+/-0.112
      mm versus 0.016+/-0.109 mm, respectively, P=0.029; max IMT, -0.084+/-0.113 mm
      versus -0.005+/-0.108 mm, respectively, P=0.0008). The baPWV was also improved
      significantly in the EPA treated group compared with the control group (-22.1+/
      127.9 cm/s versus 62.3+/-223 cm/s, respectively, P=0.021). Multiple regression
      analysis showed that the administration of EPA was a significant and independent
      factor associated with an annual improvement of mean IMT (R2=0.067). In summary,
      this is the first demonstration that administration of purified EPA improves the
      carotid IMT and the baPWV in patients with type 2 diabetes.

PMID- 16616149
TI  - Wegener's granulomatosis: more than meets the eye.

PMID- 16616150
TI  - Spontaneous pyogenic facet joint infection.
AB  - OBJECTIVE: To analyze the clinical features, approaches to management, and
      outcome of spontaneous pyogenic facet joint infection (PFJI) in adults. PATIENTS
      AND METHODS: Case series of 10 adults with microbiologically proven PFJI
      diagnosed during a 10-year period in a teaching hospital, plus a review of 32
      additional cases previously reported (PubMed 1972 to 2003). Patients with prior
      spinal instrumentation or surgery and injection drug users were excluded. Only
      cases that were sufficiently detailed to be individually analyzed were included.
      These 32 cases, together with our 10 patients, form the basis of the present
      analysis. RESULTS: PFJI represented nearly 20% of all spontaneous pyogenic spinal
      infection diagnosed in our hospital during a 10-year period. This data suggest
      that PFJI is more common than was previously thought. Of the 42 patients with
      PFJI, 26 (62%) were men and 16 (38%) were women, with ages ranging from 20 to 86
      years (mean age, 59+/-15 years); 55% of patients were older than 60 years. The
      most common location of infections was the lumbosacral region (86%). All patients
      presented with severe back pain; fever was noted in 83% of the cases and
      neurological impairment in nearly 48%. In 38% of patients a systemic predisposing
      factor for infection was present; the most common conditions were diabetes
      mellitus, malignancies, and alcoholism. In almost 36% of cases, one or more
      concomitant infectious processes due to the same microorganism was found, mainly
      arthritis, skin and soft-tissue infections, endocarditis, and urinary tract
      infections. Staphylococcus aureus was the most common etiologic microorganism
      (86% of cases). Bacteremia was documented in 81% of the cases. The diagnosis of
      PFJI was based mainly on imaging study findings. Paraspinal and/or epidural
      extension was frequent (81% of cases), but its presence did not indicate a worse
      prognosis. Medical treatment alone was usually successful. The overall prognosis
      of PFJI was good, with a mortality rate of only 2%. The great majority of
      patients were cured without functional sequelae. CONCLUSION: Incidence data from
      our institution reveal that PFJI is not a rare condition, representing
      approximately 20% of all pyogenic spinal infections. This entity should be
      considered in the differential diagnosis of patients with low back pain,
      especially in the presence of fever, whatever the patient's immunological status.

PMID- 16616151
TI  - Wegener's granulomatosis: ophthalmic manifestations and management.
AB  - OBJECTIVES: To provide an up-to-date and comprehensive review of Wegener's
      granulomatosis (WG) as a disease entity, focusing on the ophthalmic
      manifestations and management options. METHODS: A search of Medline was
      undertaken between 1966 and 2005 regarding WG, systemic vasculitis, and the
      ocular manifestations of WG. Major ophthalmic and medical textbooks also were
      reviewed for content, as well as original references. RESULTS: Involvement of
      ocular and orbital structures in patients with WG is common and may be a
      presenting feature. The ocular manifestations range from mild conjunctivitis and
      episcleritis to more severe inflammation with keratitis, scleritis, uveitis, and
      retinal vasculitis. Involvement of the nasolacrimal system and orbital tissues
      also can occur. Except for some cases of anterior segment inflammation, the
      ocular involvement will not respond to topical agents, but rather to systemic
      antiinflammatory and immunosuppressive regimens. Surgical intervention may be of
      value for obtaining tissue diagnosis, in achieving orbital decompression in cases
      of significant orbital disease with optic nerve compromise, or in cases of
      nasolacrimal duct obstruction. CONCLUSION: WG is an important clinical entity
      that needs to be recognized early and treated appropriately. Ophthalmic
      manifestations are frequently encountered and can result in significant morbidity
      and even blindness. The management is challenging and often requires a
      multidisciplinary approach.

PMID- 16616152
TI  - Fragility fractures and the osteoporosis care gap: an international phenomenon.
AB  - OBJECTIVES: To describe practice patterns in the management of osteoporosis after
      fragility fracture. METHODS: Systematic review of articles in MEDLINE, EMBASE,
      Cochrane, and CINAHL databases (1996 to February 2005). Diagnostic outcomes
      included clinical osteoporosis diagnoses, laboratory tests, and bone density
      scans. Treatment outcomes included initiation of calcium, vitamin D, hormone
      replacement therapy, bisphosphonates, calcitonin, raloxifene and falls
      assessments. RESULTS: Thirty-five studies met our inclusion criteria and
      demonstrated that adults who experience fragility fracture are not receiving
      osteoporosis management. An osteoporosis diagnosis was reported in 1 to 45% of
      patients with fractures; laboratory tests were ordered for 1 to 49% and 1 to 32%
      of patients had bone density scans. Calcium/vitamin D and pharmacological therapy
      was reported in 2 to 62% and 1 to 65% of patients, respectively. Osteoporosis
      treatment was recommended more often in women than men, and more often in
      patients with vertebral fractures than in patients with nonvertebral fractures.
      Older patients were more likely to be diagnosed with osteoporosis, but treatment
      was more likely in younger patients. A history of prior fracture was reported in
      7 to 67% of patients. Between 1 and 22% of patients had a subsequent fracture
      during follow-up periods of 6 months to 5 years. Falls assessments were not often
      reported; when they were, they were infrequently performed. A greater proportion
      of patients were diagnosed/treated during follow-up studies than in studies
      evaluating diagnosis/treatment on discharge from acute care. CONCLUSIONS: The
      majority of individuals who sustain fragility fractures are not receiving
      adequate osteoporosis management. Future research should address barriers to
      appropriate management and the efficacy of implementation strategies designed to
      close the osteoporosis care gap. RELEVANCE: This article is of particular
      importance to health care professionals who provide care for patients with
      fragility fracture.

PMID- 16616153
TI  - Characterization of T-cell large granular lymphocyte leukemia associated with
      Sjogren's syndrome-an important but under-recognized association.
AB  - OBJECTIVE: Patients with T-cell (CD3+) large granular lymphocyte (LGL) leukemia
      have a high prevalence of autoantibodies and associated autoimmune diseases.
      Sjogren's syndrome may not be diagnosed unless specifically looked for. We set to
      determine the prevalence of Sjogren's syndrome in LGL leukemia and its cytokine
      profile. METHODS: Every patient with a confirmed diagnosis of LGL leukemia
      diagnosed at a single academic medical center over the last 15 years was
      evaluated for Sjogren's syndrome by questioning about sicca symptoms. In
      symptomatic patients, Schirmer's test, rose bengal corneal staining, salivary
      flow rate measurement, autoantibody screening, and minor salivary gland biopsy
      were performed. Supernatants obtained from T-LGL leukemic cells following
      phytohemagglutinin (PHA) activation were analyzed for cytokine production by
      enzyme-linked immunosorbent assay and patients with or without Sjogren's syndrome
      were compared with controls. RESULTS: Of 48 patients, 21 reported sicca symptoms
      and were enrolled in the study. In 8 patients Sjogren's syndrome was ruled out.
      Thirteen patients had clear evidence of Sjogren's syndrome according to accepted
      criteria (27%). None had rheumatoid arthritis, but 1 had limited scleroderma.
      Thus, 12/48 patients had primary Sjogren's syndrome. Other autoimmune diseases
      were frequently present, in particular, immune cytopenias (n=7) or thyroid
      autoimmunity (n=6). Supernatants of T-LGL leukemia cells incubated with PHA
      revealed markedly increased levels of multiple cytokines (especially soluble
      interleukin 2 receptor, tumor necrosis factor alpha, IL-6, IL-8) compared with
      healthy controls. However, this increase was common to LGL leukemia patients with
      or without Sjogren's syndrome. CONCLUSIONS: Sjogren's syndrome was commonly
      identified in the patients with T-cell LGL leukemia in this study. Upregulated
      cytokine production by the neoplastic cells may underlie some of the immune
      mediated disorders common in these patients.

PMID- 16616154
TI  - Atypical autoantibodies in patients with primary Sjogren syndrome: clinical
      characteristics and follow-up of 82 cases.
AB  - OBJECTIVES: To analyze the clinical characteristics, follow-up, and fulfillment
      of classification criteria for other systemic autoimmune diseases (SAD) in
      patients with primary Sjogren syndrome (SS) and atypical autoantibodies. METHODS:
      We studied 402 patients diagnosed with primary SS seen consecutively in our
      Department since 1994. We considered anti-DNA, anti-Sm, anti-RNP, anti
      topoisomerase1/Scl70, anticentromere (ACA), anti-Jo1, anti-neutrophil cytoplasmic
      antibodies (ANCA), anticardiolipin antibodies (aPL), and lupus anticoagulant as
      atypical autoantibodies. The patients were prospectively followed after inclusion
      into the protocol, focusing on the development of features that might lead to the
      fulfillment of classification criteria for additional SAD. As a control group, we
      selected an age-sex-matched subset of patients with primary SS without atypical
      autoantibodies. RESULTS: Eighty-two (20%) patients showed atypical autoantibodies
      (36 had aPL, 21 anti-DNA, 13 ANCA, 10 anti-RNP, 8 ACA, 6 anti-Sm, 2 anti-Scl70,
      and 1 anti-Jo-1 antibodies). There were 77 (94%) women and 5 (6%) men, with a
      mean age of 57 years. Patients with atypical autoantibodies had no statistical
      differences in the prevalence of the main sicca features, extraglandular
      manifestations (except for a higher prevalence of Raynaud's phenomenon, 28%
      versus 7%, P=0.001), immunological markers, and in the fulfillment of the 2002
      classification criteria, compared with the control group. After a follow-up of
      534 patient-years, 13 (16%) of the 82 patients with atypical autoantibodies
      developed an additional SAD (systemic lupus erythematosus in 5 cases,
      antiphospholipid syndrome in 4, limited scleroderma in 3, and microscopic
      polyangiitis in 1) compared with none in the control group (P<0.001).
      CONCLUSIONS: This study shows an immunological overlap (defined by the presence
      of autoantibodies considered typical of other SAD) in 20% of our patients with
      primary SS. However, the clinical significance of these atypical autoantibodies
      varies widely depending on the autoantibodies detected, with a broad spectrum of
      prevalence and clinical patterns of disease expression, and a specific
      predilection for association with some SAD in preference to others.

PMID- 16616155
TI  - Antiphospholipid antibodies associated with malignancies: clinical and
      pathological characteristics of 120 patients.
AB  - OBJECTIVE: To describe the different types of malignancies associated with
      antiphospholipid antibodies (aPL). METHODS: We performed a computer-assisted
      (MEDLINE, National Library of Medicine, Bethesda, MD) search of the literature
      from 1966 to 2003 to identify all cases of malignancies having aPL. RESULTS: One
      hundred twenty patients were found. The mean age was 56+/-17 years (range 5 to
      88). Sixty-two (52%) patients were men and 58 (48%) were women. A heterogeneous
      group of malignancies were found. Regarding hematological malignancies, 10 (8%)
      patients suffered from B-cell lymphoma, 8 (7%) from spleen lymphoma, 7 (6%) from
      chronic myeloid leukemia, and 6 (5%) from non-Hodgkin's lymphoma (NHL). Regarding
      solid tumors, renal cell carcinoma was diagnosed in 7 (6%) patients, primary
      tumor with unknown origin in 7 (6%), lung adenocarcinoma in 6 (5%), breast
      carcinoma in 6 (5%), and melanoma in 6 (5%). The main aPL-related manifestations
      were thrombocytopenia (25%), cerebrovascular accidents (24%), deep vein
      thrombosis (19%), pulmonary embolism (15%), and heart valve lesions (9%). In 17
      cases, catastrophic antiphospholipid syndrome was considered to be triggered by
      the malignancy. Seventy-one (63%) of 113 patients recovered or are still alive
      after cancer treatment. Twenty-three (35%) of 65 patients achieved aPL remission
      after proper treatment of the malignancy. CONCLUSIONS: It is important to bear in
      mind, especially in elderly patients, that thrombotic events associated with aPL
      can be the first manifestation of malignancy. At the same time, the presence of
      aPL in patients with malignancies has important implications in their treatment
      and prognosis.

PMID- 16616156
TI  - Lack of echocardiographic and Doppler abnormalities in psoriatic arthritis
      patients without clinically evident cardiovascular disease or classic
      atherosclerosis risk factors.
AB  - OBJECTIVE: To assess the prevalence of echocardiographic and Doppler
      abnormalities in psoriatic arthritis (PsA) patients without clinically evident
      cardiovascular manifestations or classic atherosclerosis risk factors. METHODS:
      Fifty PsA patients were recruited from Hospital Xeral-Calde, Lugo, Spain.
      Patients seen during the period of recruitment that had classic cardiovascular
      risk factors or had suffered cardiovascular or cerebrovascular events were
      excluded. Fifty healthy matched controls were also studied. Echocardiographic and
      Doppler studies were performed in all cases and controls. RESULTS: In PsA
      patients the frequency of aortic and tricuspid (10%) and mitral regurgitation
      (16%) was not different from that seen in matched controls (10, 4, and 12%).
      Also, the pulmonary artery systolic pressure was normal in the group of PsA
      patients (23.4+/-3.9 mm Hg). The prevalence of diastolic dysfunction, in all
      cases due to impaired relaxation, was similar in PsA patients (28%) and controls
      (24%) (P=0.65). In addition, no significant echocardiographic and Doppler
      differences were observed when PsA patients with polyarticular pattern were
      compared with the remaining PsA patients. CONCLUSIONS: The present study shows
      that actively treated PsA patients without cardiovascular risk factors or
      clinically evident cardiovascular disease do not exhibit silent subclinical
      echocardiographic abnormalities.

PMID- 16616158
TI  - Securing an equal role for substance abuse counselors: a commentary on Kerwin,
      Walker-Smith, and Kirby.

PMID- 16616159
TI  - Enhancing the EBP repertoire of substance abuse counselors: a commentary on
      Kerwin, Walker-Smith, and Kirby.

PMID- 16616160
TI  - Comparative analysis of state requirements for the training of substance abuse
      and mental health counselors.
AB  - Data on minimum state requirements for drug and alcohol counselors and mental
      health counselors in all 50 states and Washington, DC, suggest that training as a
      mental health counselor is primarily structured through formal education, whereas
      training as a substance abuse counselor resembles an apprentice model. Fewer
      states offer or require certification or licensure of substance abuse counselors,
      compared to mental health counselors. States that do offer such credentials for
      substance abuse counselors generally require more hours of supervised work
      experience and continuing education, but fewer hours of formal course work and
      practicum courses, and a lower level of formal education. Although these
      different models for training are valid, they each have different implications
      for clinical practice, dissemination of research findings to practice, and
      management within the service delivery model.

PMID- 16616161
TI  - Unmet needs for comprehensive services in outpatient addiction treatment.
AB  - Many addiction treatment patients suffer from health and psychosocial problems in
      addition to substance misuse at the time of their treatment entry. Outpatient
      treatment programs have attempted to address these problems by providing or
      facilitating access to comprehensive health and social services. Nevertheless,
      previous research have suggested high levels of unmet needs for these services in
      the addiction treatment population. Using data from a large study on community
      based outpatient addiction treatment, this article provides additional
      information on levels of unmet service needs and the relationship between need
      and receipt of services during treatment. Our results suggest extremely high
      levels of unmet needs for a wide variety of health and psychosocial services.
      Specifically, the data suggest that unmet service needs may be far more prevalent
      than previous estimates and that addiction treatment populations in rural areas
      may be particularly disadvantaged.

PMID- 16616162
TI  - Effect of opioid substitution therapy on alcohol metabolism.
AB  - Forty opioid substitution patients (methadone, n = 14; LAAM, n = 14; and
      buprenorphine, n = 12) who were participating in a study on the impact of opiate
      substitution treatment on driving ability and 22 non-opiate-using control
      subjects were administered 14.7 g/70 kg of alcohol in two separate sessions, one
      2-3 hours before opioid pharmacotherapy dosing and the other 1-2 hours after
      dosing. The mean blood alcohol concentration (BAC) in the post-opioid dose
      session was significantly lower than that in the pre-opioid dose session (p <
      .05). There was a significant effect of experimental group (LAAM, methadone,
      buprenorphine, or control) on BAC in sessions conducted 1-2 hours after the
      opioid substitution dose (p < .01). There was a trend for a reduced effect of
      experimental group on BAC in the pre-opioid substitution dose session (p = .06).
      The BAC of non-opioid substitution control subjects was significantly higher than
      that of the LAAM (before and after LAAM dosing) and methadone (after methadone
      dosing; p < .05) patients. These findings provide evidence for the first time of
      an interaction between opiates and alcohol in humans that is strongest at the
      time of peak opiate plasma levels in the hours after opioid dosing.

PMID- 16616163
TI  - Substance-abusing mothers and disruptions in child custody: an attachment
      perspective.
AB  - Using an attachment framework, we examined (1) whether substance-abusing mothers'
      perceptions of how they were parented were related to the severity of their
      substance abuse and psychological maladjustment and (2) whether these two factors
      mediated the association between mothers' perceptions of how they were parented
      and their children's placement out of home. There were 108 mothers of 248
      children who completed interviews upon admission to a methadone maintenance
      program for women. Measures included lifetime risk composite scores derived from
      the Addiction Severity Index, the Parental Bonding Instrument, and a demographics
      questionnaire. A multilevel modeling approach was used to model effects of the
      hierarchically organized data (e.g., children nested within families). Findings
      are consistent with an attachment perspective on parenting suggesting that the
      internal psychological processes of a parent play a critical role in the
      continuity of parenting.

PMID- 16616164
TI  - Treating complicated grief and substance use disorders: a pilot study.
AB  - Empirically supported treatments for co-occurring substance use disorders (SUDs)
      and grief problems are lacking, despite the salience of grief pathology in
      substance abusers. Identification of a syndrome of complicated grief, distinct
      from bereavement-related depression and anxiety, led to the development of a
      targeted treatment, but this treatment has not been tried with persons with SUDs.
      We recruited 16 adults with complicated grief and substance dependence or abuse
      into an open pilot study of a manualized 24-session treatment, incorporating
      motivational interviewing and emotion coping and communication skills into our
      efficacious complicated grief treatment. Completer and intent-to-treat analyses
      showed significant reductions in Inventory of Complicated Grief and Beck
      Depression Inventory scores, with large effect sizes. Timeline Followback percent
      days abstinent increased significantly in both analyses, with medium to large
      effect sizes, and cravings declined significantly. Study limitations
      notwithstanding, complicated grief and substance use treatment appears to be a
      promising intervention that merits further research.

PMID- 16616165
TI  - High-dose nicotine patch therapy for smokers with a history of alcohol
      dependence: 36-week outcomes.
AB  - This study reports findings from an investigation of the efficacy of high-dose
      nicotine patch (NP) therapy for heavy smokers with a history of alcohol
      dependence. One hundred thirty participants were randomly assigned to 42 or 21 mg
      of transdermal nicotine. Follow-up assessments were conducted at 4, 12, 24, and
      36 weeks. Differences between dose conditions were nonsignificant, although,
      unexpectedly, outcomes favored participants in the 21-mg NP condition. Nicotine
      abstinence rates in the 21- and 42-mg NP conditions on Week 36 follow-up were
      16.9% and 9.2%, respectively. Patch condition did not interact with severity of
      nicotine dependence. However, nicotine abstinence at follow-up was related to a
      longer length of alcohol abstinence. No evidence was found for better outcomes as
      a function of the percentage of baseline cotinine replaced by NPs. Future
      research should focus primarily on investigating ways to improve smoking quit
      rates for smokers in early alcohol recovery.

PMID- 16616166
TI  - A 12-year follow-up of a treated cocaine-dependent sample.
AB  - The study examined long-term outcomes (mortality, substance use, mental health,
      employment, criminal involvement) among a cocaine-dependent sample. This 12-year
      follow-up study, conducted in 2002-2003, updates information obtained at intake
      and two face-to-face interviews conducted in 1990-1991 and 1991-1992 among 321
      male cocaine-dependent veterans admitted to drug treatment in 1988-1989. At the
      2002-2003 follow-up, 28 had died and 266 were interviewed. A mixed model
      examining the longitudinal relationships demonstrated that treatment was
      associated with lower levels of cocaine use over the 12-year follow-up period
      after entry into the index treatment and more stable recovery (i.e., continuously
      abstinent from cocaine for at least 5 years). Few measures at intake predicted
      stable recovery at follow-up: only being White (vs. being African American) and
      having greater confidence in ability to avoid cocaine use in high-risk
      situations. Individuals achieving stable recovery reported less psychiatric
      symptoms, criminal involvement, and unemployment during the year prior to the
      interview. Adverse outcomes were apparent for a significant number of cocaine
      dependent users who continued to use cocaine for a long period.

PMID- 16616167
TI  - Treatment barriers identified by substance abusers assessed at a centralized
      intake unit.
AB  - The 59-item Barriers to Treatment Inventory (BTI) was administered to 312
      substance abusers at a centralized intake unit following assessment but before
      treatment entry to assess their views on barriers to treatment. Factor analysis
      identified 25 items in 7 well-defined latent constructs: Absence of Problem,
      Negative Social Support, Fear of Treatment, Privacy Concerns, Time Conflict, Poor
      Treatment Availability, and Admission Difficulty. The factorial structure of the
      barriers is consistent with the findings of other studies that asked substance
      abusers about barriers to treatment and is conceptually compatible with
      Andersen's model of health care utilization. Factors were moderately to highly
      correlated, suggesting that they interact with one another. Selected
      characteristics were generally not predictive of barrier factors. Overall,
      results indicate that the BTI has good content validity and is a reliable
      instrument for assessing barriers to drug treatment. The potential utility of the
      BTI in assessment settings is discussed.

PMID- 16616168
TI  - A randomized trial of audio computer and in-person interview to assess HIV risk
      among drug and alcohol users in Rio De Janeiro, Brazil.
AB  - This study compares drug patterns and prevalence of risk behaviors in a
      randomized trial using two methods of administration, Audio Computer-Assisted
      Self-Interview (ACASI) and Interviewer-Administered Questionnaire (IAQ), among
      drug users seeking treatment in a drug treatment center. We randomized 735
      participants: 367 to ACASI and 368 to IAQ. No significant difference in
      sociodemographic variables were found between subjects in the two arms of the
      study. Those interviewed by ACASI were more likely to report use on 7 of 10
      substances assessed. Rates of reporting of sexual risk behaviors (male-to-male
      and commercial sex) were higher among participants in the ACASI arm. ACASI seems
      to be a key resource in improving the reporting of sensitive data in Brazil, as
      it has been in prior international studies.

PMID- 16616169
TI  - Therapist influence on client language during motivational interviewing sessions.
AB  - Client language in favor of change is hypothesized to be a causal mechanism for
      motivational interviewing (MI), and specific therapist behaviors are prescribed
      to elicit such speech. This project examined 38 motivational enhancement therapy
      sessions from Project MATCH (Matching Alcoholism Treatments to Client
      Heterogeneity), using a sequential behavioral coding system to investigate the
      relationship between therapist behaviors and client speech. Conditional
      probabilities were calculated between MI-consistent (MICO) therapist behaviors,
      MI-inconsistent (MIIN) therapist behaviors, and immediately subsequent client
      speech. MICO behaviors were more likely to be followed by self-motivational
      statements, whereas MIIN behaviors were more likely to be followed by client
      resistance. These results lend support to the importance of therapist behaviors
      in shaping client speech during MI sessions.

PMID- 16616170
TI  - An intervention program for ADHD in patients with substance use disorders:
      preliminary results of a field trial.
AB  - The comorbidity of attention deficit hyperactivity disorder (ADHD) is frequently
      not well recognized in substance abuse treatment institutions in The Netherlands.
      As a consequence, patients with substance use disorder (SUD) and ADHD often
      receive suboptimal treatment. To prevent every treatment center from having to
      invent its own diagnostic procedure and intervention for ADHD, a national working
      group was established. This group developed an intervention program for the
      screening, diagnosis, and treatment of ADHD in patients with SUD. This article
      describes the development and content of this intervention program. An important
      part of this development was testing the intervention program in two addiction
      treatment centers in The Netherlands. Systematic screening of ADHD was part of
      the test. A self-report questionnaire was used. Subjects with positive screening
      results were referred for the diagnostic procedure. Nine hundred twenty-eight
      screenings were performed: 207 screened positive, 115 came for further
      diagnostics, and 65 were ultimately diagnosed with ADHD.

PMID- 16616171
TI  - Person-related and treatment-related barriers to alcohol treatment.
AB  - Treatment underutilization by persons with alcohol use disorder is well
      documented. This study examined barriers to treatment at the latter stages of the
      treatment-seeking process, which was conceptualized as recognizing the problem,
      deciding that change is necessary, deciding that professional help is required,
      and seeking care. All participants identified themselves as having a drinking
      problem that was severe enough to warrant treatment. Differences between those
      who had (Treatment Seekers) and those who had not (Comparison Controls) sought
      treatment were evaluated, including the experience of person-related (e.g.,
      shame) and treatment-related (e.g., cost) barriers. Person-related barriers were
      more commonly endorsed by both groups than treatment-related barriers. Comparison
      Controls were more likely to endorse both types of barriers, especially the
      preference for handling the problem without treatment. Treatment-related barriers
      were less relevant than person-related barriers at the latter stage of help
      seeking. The significance of barriers endured after accounting for other
      differences, such as drinking-related negative consequences. Treatment
      implications are discussed.

PMID- 16616172
TI  - Knowledge and use of the internet as a source of controlled substances.
AB  - Despite growing evidence that the internet is a source of controlled substances
      for nonmedical use, there is a lack of information about who is using it to
      obtain these drugs. One hundred adult drug-dependent inpatients in a private
      residential treatment program participated in a semistructured interview
      regarding how they obtained their drugs. Twenty-nine percent reported knowledge
      of the internet as a source of drugs, and 11% reported that they had used the
      internet to either buy drugs or locate a drug dealer. The results of this
      preliminary study suggest that the internet has become a source of controlled
      substances for some addicted individuals. Considerations for future research and
      clinical practice are described.

PMID- 16616173
TI  - Osteoblast response to the elastic strain of metallic support.
AB  - It is known that metallic elements of joint endoprostheses undergo elastic strain
      due to their mechanical function. This is one of the factors which may be
      responsible for the loosening of endoprostheses. Since mechanisms involved in it
      remain unclear, it seems valuable to verify if cells responsible for bone
      regeneration are affected by a strain of the implant. Our experiment examines the
      influence of elastic strain applied to Ti6Al4V samples on osteoblasts cultured on
      their surface in vitro. Human bone-derived cells are observed in contact with
      metallic plates. Titanium alloy was chosen as a support since it is one of the
      most commonly used materials for stems in joint endoprostheses. Cyclic elastic
      deformation of 0.1% was applied to the support once daily for 7 days. Two
      thousand cycles were applied each time. Samples which were not subject to strain
      served as control. After the observation period XTT assay was performed, alkaline
      phosphatase activity as well as osteocalcin concentration and nitric oxide
      secretion were determined and compared with the results obtained in the control
      group. It was found that the number of viable cells in the mechanically
      stimulated population was significantly higher than in control, while both
      alkaline phosphatase activity and osteocalcin concentration were significantly
      lower in the experimental group. Nitric oxide secretion was found in the culture
      which was subject to elastic strain, but not in the control. The possible
      clinical implication is that elastic strain of the metallic endoprostheses may
      influence osteoblasts which are in contact with the implant in vivo.

PMID- 16616174
TI  - Gas chromatographic-mass spectrometric analysis of essential oils from Pimpinella
      species gathered from Central and Northern Turkey.
AB  - Essential oils from 15 Pimpinella species were analyzed by gas chromatography
      (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. One species,
      Pimpinella anisum, in which only fruits were evaluated, was also included in the
      study. A total of 140 different compounds were identified and significant
      qualitative and quantitative differences were observed among the samples.
      Pimpinella essential oils were characterized as having mono-, sesqui- and
      trinorsesquiterpenoids, propenylphenols, and pseudoisoeugenols.
      Trinorsesquiterpenoids and phenylpropanoids appear to be chemical markers of
      Pimpinella species analyzed thus far. Essential oils obtained from Pimpinella
      roots share the same principal compound, epoxypseudoisoeugenyl-2-methylbutyrate
      at concentrations from 20 to 82.6%.

PMID- 16616175
TI  - Novel imidazolium stationary phase for high-performance liquid chromatography.
AB  - A new imidazolium anion-exchange phase immobilized on silica is synthesized. HPLC
      separations of common inorganic anions (IO3-, Cl-, NO2-, Br-, NO3-, I-, SCN-)
      have been performed using a HPLC column (200 mm x 4.6 mm I.D.) packed with this
      stationary phase, with a phosphate buffer solution as the mobile phase and UV
      detection at 200 nm. The effects of pH and concentration of eluent on the
      separation of anions have been studied. Chromatographic parameters are calculated
      and the results show that the new stationary phase is of significant potential
      for the analysis of these anions. Successful separations of some ordinary organic
      anions have also been achieved with the said stationary phase. Meaningfully,
      organic and inorganic anions can be determined simultaneously and satisfactorily
      with several neutral compounds using the column. The separation of some organic
      compounds including hydroxybenzenes, bases and amines by this stationary phase
      with only water as the eluent has been investigated.

PMID- 16616176
TI  - Achieving rapid low-pressure ion chromatography separations on short silica-based
      monolithic columns.
AB  - Short silica-based monolithic columns (0.5-1 cm) are coated with the surfactant
      didodecyldimethylammonium bromide (DDAB) and used for fast ion exchange
      separations of small inorganic anions. Sources of extra-column band broadening
      are assessed and minimized to obtain separations of seven analytes (iodate,
      chloride, nitrate, bromide, nitrite, phosphate, sulphate) in two minutes at 2
      mL/min. Eluents used are 6 and 9 mM 4-cyanophenol at pH 7.3-7.4 or 5 mM 4
      hydroxybenzoic acid at pH 5.6. DDAB coating stability is improved by 15-fold by
      the addition of a DDAB coated pre-column before the injection valve. Separations
      are obtained using a low-pressure glass syringe.

PMID- 16616177
TI  - Exploration of coordination polymer as sorbent for flow injection solid-phase
      extraction on-line coupled with high-performance liquid chromatography for
      determination of polycyclic aromatic hydrocarbons in environmental materials.
AB  - The copper(II) isonicotinate (Cu(4-C5H4N-COO)2(H2O)4) coordination polymer was
      prepared, characterized and explored as sorbent for flow injection solid-phase
      extraction on-line coupled with high-performance liquid chromatography (HPLC) for
      determination of trace polycyclic aromatic hydrocarbons (PAHs) in environmental
      matrices. Naphthalene, phenanthrene, anthracene, fluoranthene,
      benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene and benzo(ghi)perylene
      with various shape, size and hydrophobicity were used as model analytes. The
      porosity of the coordination polymer allows these guest PAHs molecules to diffuse
      into the buck structure, and the shape and size of the pores lead to shape- and
      size-selectivity over the guests. The precolumn packed with the coordination
      polymer was shown to be promising for solid-phase extraction of PAHs in
      environmental samples with subsequent HPLC separation and UV detection. With
      extraction of 50 ml of sample solution, the enhancement factors for the PAHs
      studied ranged from 200 to 2337, depending on the shape, size and hydrophobic
      property of the PAHs. The detection limits (S/N = 3) of 2-14 ng l(-1) and the
      sample throughput of 3 samples h(-1) were obtained. The developed method was
      applied to the determination of trace PAHs in a certified reference material
      (coal fly ash) and local water samples.

PMID- 16616178
TI  - Single, binary, and multicomponent sorption of iron and manganese on lignite.
AB  - Acid mine drainage (AMD) has long been a significant environmental problem
      resulting from the microbial oxidation of iron pyrite in the presence of water
      and air, affording an acidic solution that contains toxic metal ions. The main
      objective of this study was to remove metal ions [Fe(II), Fe(III), Mn(II),
      Zn(II)] from AMD using lignite, a low-cost adsorbent. The lignite sorbent was
      utilized for the sorption of ferrous, ferric, manganese, zinc, and calcium ions
      in aqueous solutions. Studies were performed at different pH to find optimum pH.
      Equilibrium isotherms were determined to assess the maximum adsorption capacity
      of lignite for different metal ions. Sorption capacities were compared in single,
      binary, ternary, and multicomponent systems. The sorption data are correlated
      with Freundlich and Langmuir isotherms in each system. Both Freundlich and
      Langmuir isotherms fit the data reasonably well in terms of regression
      coefficients. Sorption studies were also performed at different temperatures to
      obtain the thermodynamic parameters of the process. The maximum lignite
      adsorption capacities at 25 degrees C were 34.22, 25.84, and 11.90 mg/g for
      Fe(II), Mn(II), and Fe(III), respectively. Adsorption of Fe(2+) (24.70 mg/g at 10
      degrees C and 46.46 mg/g at 40 degrees C) increased with increased temperature,
      while Mn(2+) adsorption (28.11 mg/g at 10 degrees C and 7.70 mg/g at 40 degrees
      C) decreased with increased temperature.

PMID- 16616179
TI  - Synthesis of micrometer-sized hard silica spheres with uniform mesopore size and
      textural pores.
AB  - Micrometer-sized silica spheres were prepared using a new pH-induced rapid
      colloid aggregation method in water-in-oil (W/O) emulsion separately with F127
      and the mixture of Pluronic triblock copolymer (F127, P123, or P105) and PEG20000
      as templates. All the mesoporous silica spheres exhibited high surface areas (657
      1145 m2/g) and large pore volumes (0.46-2.16 ml/g). Through optimizing the
      synthetic conditions, hard silica spheres with narrow particle size distribution,
      uniform pore size, and textural pores were obtained. Finally, the mechanism of
      this synthetic route is discussed.

PMID- 16616180
TI  - Effect of ionic environments on the adsorption and diffusion characteristics of
      serine alkaline protease enzyme in polyethersulfone ultrafiltration membranes.
AB  - Static adsorption of serine alkaline protease (SAP) enzyme on hydrophobic
      polyether sulfone (PES) ultrafiltration membranes in different ionic environments
      was investigated. The amount of SAP adsorbed on membranes was the lowest at its
      isoelectric point (IEP) where the maximum adsorption was obtained below the IEP
      of the enzyme. The extent of SAP adsorption in the phosphate buffer solutions
      including different salts followed the order: (NH4)2HPO4 > KH2PO4 > Na2HPO4
      NaH2PO4 (buffer) > CaCl2 > ((NH4)2HPO4 + H2PO4 + CaCl2), which was consistent
      with the Hofmeister series. The zeta potentials of membranes contacted with the
      ionic species were calculated by streaming potential measurements and found that
      the increase in ionic strength decreased the electrical double layer thickness
      leading to a decrease in adsorption. A model based on mass balance was developed
      to calculate the diffusion coefficient of SAP in PES membranes. Employing
      experimental data evaluated in a diffusion cell along with the data of adsorption
      isotherms, diffusion coefficients of SAP in PES membranes in the presence of
      different ionic species were calculated. To detect the structural changes
      occurred, membrane surfaces were analysed by Fourier transform infrared
      attenuated total reflectance (FTIR-ATR) measurements.

PMID- 16616181
TI  - The influence of ionic and nonionic surfactants on aggregative stability and
      electrical surface properties of aqueous suspensions of titanium dioxide.
AB  - The influence of concentration of nonionic TRITON X-100 and anionic ATLAS G-3300
      surfactants, and pH of medium on the size and zeta-potential of TiO2 particles in
      the water suspensions has been studied. Suspensions have been prepared by mixing
      of the titanium dioxide in the suitable mediums at 10 min and 6 h
      correspondingly. It was established, that the duration of mixing of the
      suspensions has an essential influence on the dependence of zeta-potential and
      size of particles versus concentration of surfactant. However, the duration of
      mixing does not influence the dependence of electrical conductivity and pH of the
      suspensions on concentration of surfactant. It is shown that anionic ATLAS G-3300
      surfactant is more effective stabilizator of aqueous suspensions of titanium
      dioxide, than nonionic surfactants of TRITON X-100. It is found that hydrophobic
      interaction has important role in the processes of stabilization of suspensions
      for nonionic surfactant, and for anionic surfactant--moving of psi(delta)-planes
      into solution's depth.

PMID- 16616182
TI  - Evidences of segregated SnO2 type nanoparticles coating layered double hydroxide
      at moderate temperature.
AB  - A series of layered double hydroxide (LDH) materials prepared by classical
      coprecipitation in the presence of divalent Co2+, trivalent Al3+, and tetravalent
      Sn4+ cations have been investigated as a function of the temperature. As
      illustrated for the cation composition (Co; Al; Sn) of (0.75; 0.175; 0.075), the
      segregation of SnO2-type nanodomains in an interphasing LDH sand-rose region is
      directly evidenced by transmission electron microscopy and selected area electron
      diffraction (TEM/SAED). At moderate temperature (400 degrees C) the local
      environment around the cobalt cations is strongly modified, whereas the local
      structure is found to be unchanged in the vicinity of the tin cations. It is
      explained on the basis of the breakdown of the lamellar assembly and of the
      partial oxidation of Co2+ cations and that tin dioxide domains are still
      segregated from LDH particles. Even if the tin dioxide component does not
      participate from a structural point of view in the LDH composition, its
      beneficial effect on the textural properties is significant, increasing the
      specific surface area and narrowing the pore size distribution.

PMID- 16616183
TI  - The ionic strength effect on microcystin and natural organic matter surrogate
      adsorption onto PAC.
AB  - This work aims to contribute to a better understanding of the ionic strength
      effect on microcystin and natural organic matter (NOM) surrogate adsorption by
      analyzing the importance of adsorbate molecular size, and surface concentration.
      Adsorption kinetics and/or isotherms were performed on PAC Norit SA-UF for four
      microcystin variants (MC-LR, MC-LY, MC-LW, MC-LF), and three NOM surrogates
      (salicylic acid (SA), tannic acid (TA), Aldrich humic acid (AHA)) at different
      solution ionic strengths. Results showed that the ionic strength effect depends
      upon the adsorbate surface concentration, cation charge (mono or divalent), and
      adsorbate molecular size. Potassium seemed not to affect the MC-LR adsorption,
      while calcium enhanced MC-LR kinetics and adsorption capacity. K+ and,
      particularly, Ca2+ improved the adsorption kinetics of the other microcystin
      variants. For identical surface concentration and ionic strength, the impact of
      K+ and Ca2+ on NOM surrogates depended on the adsorbate molecular size: K+ effect
      was only observed for AHA, whereas Ca2+ caused no effect on SA adsorption,
      slightly enhanced TA adsorption, and greatly enhanced AHA adsorption. MC-LR
      isotherms with two salt concentrations (KCl or CaCl2) indicated that, for the
      studied range of equilibrium surface concentration (5.3-18.7 mg/g), an enhanced
      adsorption regime prevails, and no transition regime was observed.

PMID- 16616184
TI  - Exploratory analysis of climate data using source separation methods.
AB  - We present an example of exploratory data analysis of climate measurements using
      a recently developed denoising source separation (DSS) framework. We analyzed a
      combined dataset containing daily measurements of three variables: surface
      temperature, sea level pressure and precipitation around the globe, for a period
      of 56 years. Components exhibiting slow temporal behavior were extracted using
      DSS with linear denoising. The first component, most prominent in the interannual
      time scale, captured the well-known El Nino-Southern Oscillation (ENSO)
      phenomenon and the second component was close to the derivative of the first one.
      The slow components extracted in a wider frequency range were further rotated
      using a frequency-based separation criterion implemented by DSS with nonlinear
      denoising. The rotated sources give a meaningful representation of the slow
      climate variability as a combination of trends, interannual oscillations, the
      annual cycle and slowly changing seasonal variations. Again, components related
      to the ENSO phenomenon emerge very clearly among the found sources.

PMID- 16616185
TI  - Use of a neuro-variational inversion for retrieving oceanic and atmospheric
      constituents from satellite ocean colour sensor: application to absorbing
      aerosols.
AB  - This paper presents a new development of the NeuroVaria method. NeuroVaria
      computes relevant atmospheric and oceanic parameters by minimizing the difference
      between the observed satellite reflectances and those computed from radiative
      transfer simulations modelled by artificial neural networks. Aerosol optical
      properties are computed using the Junge size distribution allowing taking into
      account highly absorbing aerosols. The major improvement to the method has been
      to implement an iterative cost function formulation that makes the minimization
      more efficient. This implementation of NeuroVaria has been applied to sea-viewing
      wide field-of-view sensor (SeaWiFS) imagery. A comparison with in situ
      measurements and the standard SeaWiFS results for cases without absorbing
      aerosols shows that this version of NeuroVaria remains consistent with the
      former. Finally, the processing of SeaWiFS images of a plume of absorbing
      aerosols off the US East coast demonstrate the ability of this improved version
      of NeuroVaria to deal with absorbing aerosols.

PMID- 16616186
TI  - The crystal structure of Cdc42 in complex with collybistin II, a gephyrin
      interacting guanine nucleotide exchange factor.
AB  - The synaptic localization of ion channel receptors is essential for efficient
      synaptic transmission and the precise regulation of diverse neuronal functions.
      In the central nervous system, ion channel receptors reside in the postsynaptic
      membrane where they are juxtaposed to presynaptic terminals. For proper function,
      these ion channels have to be anchored to the cytoskeleton, and in the case of
      the inhibitory glycine and gamma-amino-butyric acid type A (GABA(A)) receptors
      this interaction is mediated by a gephyrin centered scaffold. Highlighting its
      central role in this receptor anchoring scaffold, gephyrin interacts with a
      number of proteins, including the neurospecific guanine nucleotide exchange
      factor collybistin. Collybistin belongs to the Dbl family of guanine nucleotide
      exchange factors, occurs in multiple splice variants, and is specific for Cdc42,
      a small GTPase belonging to the Rho family. The 2.3 Angstroms resolution crystal
      structure of the Cdc42-collybistin II complex reveals a novel conformation of the
      switch I region of Cdc42. It also provides the first direct observation of
      structural changes in the relative orientation of the Dbl-homology domain and the
      pleckstrin-homology domain in the same Dbl family protein. Biochemical data
      indicate that gephyrin negatively regulates collybistin activity.

PMID- 16616187
TI  - Crystal structure of human vascular endothelial growth factor-B: identification
      of amino acids important for receptor binding.
AB  - The development of blood vessels (angiogenesis) is critical throughout
      embryogenesis and in some normal postnatal physiological processes. Pathological
      angiogenesis has a pivotal role in sustaining tumour growth and chronic
      inflammation. Vascular endothelial growth factor-B (VEGF-B) is a member of the
      VEGF family of growth factors that regulate blood vessel and lymphatic
      angiogenesis. VEGF-B is closely related to VEGF-A and placenta growth factor
      (PlGF), but unlike VEGF-A, which binds to two receptor tyrosine kinases VEGFR-1
      (Flt-1) and VEGFR-2 (Flk-1/KDR), VEGF-B and PlGF bind to VEGFR-1 and not VEGFR-2.
      There is growing evidence of a role for VEGF-B in physiological and pathological
      blood vessel angiogenesis. VEGF-B may provide novel therapeutic strategies for
      the treatment of vascular disease and be a potential therapeutic target in
      aberrant vessel formation. To help understand at the molecular level the
      differential receptor binding profile of the VEGF family of growth factors we
      have determined the crystal structure of human VEGF-B(10-108) at 2.48 Angstroms
      resolution. The overall structure is very similar to that of the previously
      determined cysteine-knot motif growth factors: VEGF-A, PlGF and platelet-derived
      growth factor-B (PDGF-B). We also present a predicted model for the association
      of VEGF-B with the second domain of its receptor, VEGFR-1. Based on this
      interaction and the present structural data of the native protein, we have
      identified several putative residues that could play an important role in
      receptor recognition and specificity.

PMID- 16616188
TI  - Identification of the key LMO2-binding determinants on Ldb1.
AB  - The overexpression of LIM-only protein 2 (LMO2) in T-cells, as a result of
      chromosomal translocations, retroviral insertion during gene therapy, or in
      transgenic mice models, leads to the onset of T-cell leukemias. LMO2 comprises
      two protein-binding LIM domains that allow LMO2 to interact with multiple protein
      partners, including LIM domain-binding protein 1 (Ldb1, also known as CLIM2 and
      NLI), an essential cofactor for LMO proteins. Sequestration of Ldb1 by LMO2 in T
      cells may prevent it binding other key partners, such as LMO4. Here, we show
      using protein engineering and enzyme-linked immunosorbent assay (ELISA)
      methodologies that LMO2 binds Ldb1 with a twofold lower affinity than does LMO4.
      Thus, excess LMO2 rather than an intrinsically higher binding affinity would lead
      to sequestration of Ldb1. Both LIM domains of LMO2 are required for high-affinity
      binding to Ldb1 (K(D) = 2.0 x 10(-8) M). However, the first LIM domain of LMO2 is
      primarily responsible for binding to Ldb1 (K(D) = 2.3 x 10(-7) M), whereas the
      second LIM domain increases binding by an order of magnitude. We used mutagenesis
      in combination with yeast two-hybrid analysis, and phage display selection to
      identify LMO2-binding "hot spots" within Ldb1 that locate to the LIM1-binding
      region. The delineation of this region reveals some specific differences when
      compared to the equivalent LMO4:Ldb1 interaction that hold promise for the
      development of reagents to specifically bind LMO2 in the treatment of leukemia.

PMID- 16616190
TI  - Neutralize MCI chaos.

PMID- 16616189
TI  - Nestin immunoreactivity of Purkinje cells in Creutzfeldt-Jakob disease.
AB  - Nestin, an intermediate filament protein, is mainly expressed in neural
      progenitor/stem cells in the central nervous system. Recently, we reported that
      nestin is expressed in Purkinje cells in patients with Creutzfeldt-Jakob disease
      (CJD). In this study, we examined a total of 19 CJD cerebella to analyze the
      intensity and pattern of nestin immunoreactivity of Purkinje cells in different
      pathological stages of degeneration in the cerebellar cortex. The results showed
      that the Purkinje cells were immunoreactive with nestin regardless of the
      severity of degenerative cerebellar cortex. Furthermore, we noted several
      different types of nestin immunoreactivity, indicated by diffuse and fine,
      coarse, and inclusion-like immunostainings within Purkinje cell bodies as well as
      dot-like staining outside of the cell bodies. In contrast, on examination of
      cerebella from non-CJD patients, 6 of 30 cases showed nestin immunoreactivity to
      a lesser extent. Thus, nestin-positive Purkinje cells are more common in CJD
      cerebella than in non-CJD cerebella. Although the mechanism of nestin expression
      in Purkinje cells is not yet understood, we suggest that such nestin-positive
      Purkinje cells are being reactivated to survive the cell death.

PMID- 16616195
TI  - Bias busted.

PMID- 16616197
TI  - CMS opinion frees up ambulances.

PMID- 16616198
TI  - No keddin'? Key to this device is in the details.

PMID- 16616199
TI  - Can't get no satisfaction?

PMID- 16616200
TI  - Orchestrating the fast moving MCI. Tips to help you easily manage multiple
      patient incidents of any size.

PMID- 16616201
TI  - Transformational leadership. A positive approach to EMS management.

PMID- 16616204
TI  - Application of FTTP to alpha-helix or beta-strand motifs.
AB  - Information concerning protein structure is widely dispersed and cannot easily
      and rapidly be processed by the biological community. We present a database of
      tendentious factors of three states of tripeptide units from PDB database, called
      a bank of tendentious factors of three states of three-peptide units (FTTP). The
      FTTP database was constructed based on conformational dihedral angle (varphi,psi)
      library of 20(3) peptide triplets by exhaustively searching through PDB
      databases. We introduce the FTTP database for the analysis of characteristics
      common to relative conformational biases of all peptide triplets, especially
      finding some motifs apt to alpha-helix and beta-strand. Our results show that
      this will provide a platform for studies of short peptide motifs, folding codons,
      secondary structure and three-dimensional (3D) structure of proteins. Moreover,
      FTTP is a unique resource that will allow a comprehensive characterization of
      peptide triplets and thus improve our understanding of sequence-structure
      relationship, refined domains, 3D structures, and their associated function. We
      believe the FTTP database will help biologists in increasing the efficiency of
      finding useful and relevant information regarding structure-function relationship
      of proteins. Therefore, this approach will play an important role in protein
      folding, protein engineering, molecular design, and proteomics.

PMID- 16616205
TI  - Optimality models of phage life history and parallels in disease evolution.
AB  - Optimality models constitute one of the simplest approaches to understanding
      phenotypic evolution. Yet they have shortcomings that are not easily evaluated in
      most organisms. Most importantly, the genetic basis of phenotype evolution is
      almost never understood, and phenotypic selection experiments are rarely
      possible. Both limitations can be overcome with bacteriophages. However, phages
      have such elementary life histories that few phenotypes seem appropriate for
      optimality approaches. Here we develop optimality models of two phage life
      history traits, lysis time and host range. The lysis time models show that the
      optimum is less sensitive to differences in host density than suggested by
      earlier analytical work. Host range evolution is approached from the perspective
      of whether the virus should avoid particular hosts, and the results match optimal
      foraging theory: there is an optimal "diet" in which host types are either
      strictly included or excluded, depending on their infection qualities.
      Experimental tests of both models are feasible, and phages provide concrete
      illustrations of many ways that optimality models can guide understanding and
      explanation. Phage genetic systems already support the perspective that lysis
      time and host range can evolve readily and evolve without greatly affecting other
      traits, one of the main tenets of optimality theory. The models can be extended
      to more general properties of infection, such as the evolution of virulence and
      tissue tropism.

PMID- 16616206
TI  - A reduced mathematical model of the acute inflammatory response II. Capturing
      scenarios of repeated endotoxin administration.
AB  - Bacterial lipopolysaccharide (LPS; endotoxin) is a potent immunostimulant that
      can induce an acute inflammatory response comparable to a bacterial infection.
      Experimental observations demonstrate that this biological response can be either
      blunted (tolerance) or augmented (potentiation) with repeated administration of
      endotoxin. Both phenomena are of clinical relevance. We show that a four
      dimensional differential equation model of this response reproduces many
      scenarios involving repeated endotoxin administration. In particular, the model
      can display both tolerance and potentiation from a single parameter set, under
      different administration scenarios. The key determinants of the outcome of our
      simulations are the relative time-scales of model components. These findings
      support the hypothesis that endotoxin tolerance and other related phenomena can
      be considered as dynamic manifestations of a unified acute inflammatory response,
      and offer specific predictions related to the dynamics of this response to
      endotoxin.

PMID- 16616207
TI  - Management of BCG "Failures".

PMID- 16616208
TI  - The effect of IL-1beta on the expression of inflammatory cytokines and their
      receptors in human chondrocytes.
AB  - Cytokines released at sites of inflammation and infection can alter the normal
      processes of cartilage turnover, resulting in pathologic destruction or
      formation. Interleukin (IL)-1beta plays a central role in the pathophysiology of
      cartilage damage and degradation in arthritis. In the present study, we examined
      the effect of IL-1beta on the expression of IL-1beta, IL-6, IL-8, IL-11, tumor
      necrosis factor-alpha (TNF-alpha), and their receptors in human chondrocytes. The
      cells were cultured either with or without 100 U/ml of IL-1beta for up to 28
      days. The level of expression of the cytokines and their receptors was estimated
      by determining mRNA levels using real-time PCR or by determining protein levels
      using ELISA. The expression of IL-1beta, IL-8, and TNF-alpha markedly increased
      in the presence of IL-1beta after day 14 of culture. The expression of IL-6 and
      IL-11 increased greatly in the presence of IL-1beta on day 1 and after day 14 of
      culture. The expression of IL-1beta, IL-8, IL-11, and TNF-alpha receptors
      significantly decreased in the presence of IL-1beta after day 14 of culture,
      whereas the expression of IL-6 receptor significantly increased. The expression
      of these cytokines, except for IL-6, decreased with the addition of human IL-1
      receptor antagonist. These results suggest that IL-1beta promotes the resolution
      system of cartilage matrix turnover through an increase in inflammatory cytokine
      production by chondrocytes and that it also may promote the autocrine action of
      IL-6 through an increase in IL-6 receptor expression in the cells.

PMID- 16616209
TI  - Inducible nitric oxide synthase and cyclooxgenase-2 mediate protection of
      hydrogen peroxide preconditioning against apoptosis induced by oxidative stress
      in PC12 cells.
AB  - The induction of inducible nitric oxide synthase (iNOS) in response to different
      stress is associated with simultaneous induction of cyclooxygenase-2 (COX-2) in
      various cell types. Both iNOS and COX-2 have been reported to mediate the late
      phase of cardioprotection induced by different preconditioning. However, whether
      both iNOS and COX-2 are mediators in the neuroprotection induced by
      preconditioning with hydrogen peroxide (H(2)O(2)) at low concentration is
      unknown. In this study, using the neurosecretory cell line-PC12 cells to set up
      the model of neuroprotection of preconditioning with H(2)O(2) against apoptosis,
      we first investigate what changes in expression of iNOS and COX-2 appear during
      H(2)O(2) preconditioning, then determine if both iNOS inhibitor and COX-2
      inhibitor interfere with the neuroprotection elicited by preconditioning with
      H(2)O(2). We found that preconditioning with H(2)O(2) at 10 microM significantly
      protected PC12 cells against apoptosis induced by lethal H(2)O(2) (50 microM) and
      increased the expression of iNOS and COX-2 and that selective iNOS inhibitor,
      aminoguanidine (AG) and COX-2 inhibitor, NS-398 obviously blocked the protective
      effects induced by preconditioning with 10 microM H(2)O(2). The results of this
      study suggest that both iNOS and COX-2 are mediators of the neuroprotection
      induced by preconditioning with oxidative stress (H(2)O(2) at low concentration)
      in PC12 cells.

PMID- 16616210
TI  - DITPA restores the repolarizing potassium currents Itof and Iss in cardiac
      ventricular myocytes of diabetic rats.
AB  - Diabetes Mellitus (DM) can produce an increase in the cardiac action potential
      duration and QT interval that can be associated with sudden death. These cardiac
      effects are due to a region-specific decrease in repolarizing outward K(+)
      currents. Some authors have suggested that the proarrhythmic effects of diabetes
      can be due to diabetes-induced hypothyroidism. Thus, we have examined the effect
      of the thyroid hormone analog diiodothyropropionic acid (DITPA) on calcium
      independent outward potassium currents in ventricular myocytes from diabetic
      rats. Sustained (I(ss)) and fast transient outward (I(tof)) K(+) currents were
      recorded using the whole-cell configuration of the patch-clamp technique.
      Myocytes were enzymatically isolated from the free wall of the right ventricle,
      and the epicardial and endocardial layers of the left ventricle of healthy,
      diabetic and DITPA-treated diabetic rats. Circulating thyroid hormones were
      measured by electrochemiluminescence. DITPA-treatment of diabetic rats restored
      I(tof) and I(ss) current densities in cardiac myocytes from the three regions
      studied, but did not alter current densities in myocytes of control rats. T(3)
      and T(4) levels were reduced by diabetes, and DITPA-treatment increased
      circulating T(3) levels. T(3)-treatment of diabetic rats also restored current
      densities to control values. However, direct incubation of diabetic myocytes with
      DITPA did not restore current densities. In summary, DITPA-treatment of diabetic
      rats restored the potassium current (I(tof) and I(ss)) densities in myocytes from
      all ventricular regions.

PMID- 16616211
TI  - Clofibrate treatment promotes branched-chain amino acid catabolism and decreases
      the phosphorylation state of mTOR, eIF4E-BP1, and S6K1 in rat liver.
AB  - Leucine stimulates protein synthesis by modulating the mammalian target of
      rapamycin (mTOR) signaling pathway. We hypothesized that promotion of the
      branched-chain amino acid (BCAA) catabolism might influence the leucine-induced
      protein synthesis. Clofibric acid (an active metabolite of clofibrate) is known
      to promote the BCAA catabolism by activation of branched-chain alpha-keto acid
      dehydrogenase complex (BCKDC), the rate-limiting enzyme of the BCAA catabolism.
      In the present study, we examined the phosphorylation state of mTOR, eukaryotic
      initiation factor 4E-binding protein-1 (4E-BP1), and ribosomal protein S6 kinase
      1 (S6K1) in liver of rats with or without activation of the BCKDC by clofibrate
      treatment. Clofibrate-treated rats were prepared by oral administration of
      clofibrate 5 h before sacrifice. In order to stimulate phosphorylation of
      components in the mTOR signaling pathway, rats were orally administered with
      leucine 1 h before sacrifice. Clofibrate treatment almost fully activated hepatic
      BCKDC and significantly decreased the plasma leucine concentration in rats
      without leucine administration, resulting in decreased mTOR and 4E-BP1
      phosphorylation. Similarly, in rats administered with leucine, clofibrate
      treatment attenuated the predicted increase in plasma leucine concentration as
      well as the phosphorylation of mTOR, 4E-BP1, and S6K1. These results suggest that
      BCAA catabolism enhanced by clofibrate treatment has significant influences on
      the leucine-induced activation of translation initiation processes.

PMID- 16616212
TI  - Both endothelium and afferent nerve endings play a role in acetylcholine-induced
      renal vasodilation.
AB  - We investigated the nature and signaling pathways of endothelium- and sensory
      nerve ending-derived substances involved in acetylcholine-induced vasodilation in
      rat isolated perfused kidney. Endothelial denudation by Triton X-100 (0.2%, 0.1
      ml) or depletion of afferent nerve endings by capsaicin (10(-6) mol/l) attenuated
      acetylcholine-induced vasodilation. When these two agents were administered
      together, the response to acetylcholine was completely inhibited. CGRP1 receptor
      blocker CGRP 8-37 (10(-7) mol/l) and adenosine A(2) receptor antagonist ZM 241
      385 (10(-7) mol/l) inhibited acetylcholine-induced dilation. When indomethacin
      (10(-5) mol/l), a cyclooxygenase inhibitor, l-NOARG (10(-4) mol/l), a nitric
      oxide (NO) synthase inhibitor, and potassium chloride (30 mmol/l), to test EDHF
      response, were perfused simultaneously, the inhibition was greater than that was
      observed with each agent alone. Guanylate cyclase inhibitor ODQ (10(-5) mol/l) or
      protein kinase A inhibitor KT 5720 (5x10(-7) mol/l) inhibited acetylcholine
      induced dilation. Gap junction uncoupler 18alpha-glycyrrhetinic acid (10(-4)
      mol/l) caused an uncontrollable increase in basal perfusion pressure making it
      impossible to test against acetylcholine-induced dilation. Our data suggest that
      NO, prostanoids, EDHF, and CGRP released from vascular endothelium and afferent
      nerve endings participate in acetylcholine-induced vasodilation and their signal
      transduction molecules include protein kinase A and guanylate cyclase.

PMID- 16616213
TI  - Asymptotics and bioavailability in a 17-compartment pharmacokinetic model with
      enterohepatic circulation and remetabolization.
AB  - A 17-compartment linear pharmacokinetic model is designed, describing the complex
      process of enterohepatic circulation as a superposition of the net
      (remetabolizationfree) enterohepatic circulation, and remetabolization with
      subsequent intestinal absorption of the parent drug. Basically, the model is
      built by doubling the model describing the circulation of the parent drug in the
      body, so that the remetabolizable metabolite circulates in a model of the same
      structure as does the parent compound. The two submodels are cross-connected with
      arrows denoting the transition of the particular substance into the complementary
      part of the complex model. Asymptotic properties of the model are investigated,
      in particular, explicit formulas for its pharmacokinetic endpoints are given
      using the elements of its transition probability matrix. Conversely, taking
      account of the effect of bile cannulation, intravenous, intraportal and oral
      administration of the drug, as well as of the intravenous and intraportal
      administration of the remetabolizable metabolite, the transition probabilities of
      the system are determined in terms of certain measurable pharmacokinetic
      endpoints and the flow rates through the kidneys, liver and the cardiac output.
      Finally, the influence of the enterohepatic circulation and remetabolization
      process on bioavailability is examined. In particular, the inclusion-exclusion
      formula is derived, expressing its joint efficiency (defined as the relative
      increase of bioavailability) by means of the efficiencies of the net
      enterohepatic circulation and of the remetabolization process.

PMID- 16616214
TI  - Role of noradrenergic and GABA-ergic inputs in pedunculopontine tegmentum for
      regulation of rapid eye movement sleep in rats.
AB  - Rapid eye movement (REM) sleep disturbance is associated with several psycho
      behavioral disorders, hence, it is important to understand its neural mechanism
      of regulation. Although it was known that the noradrenergic (NA-ergic) neurons
      from locus coeruleus (LC) project to the pedunculopontine tegmentum (PPT), the
      role of noradrenaline (NA) alone and in association with GABA, an inhibitory
      neurotransmitter, in PPT for REM sleep regulation was not known and was
      investigated in this study in freely moving normally behaving rats. Rats were
      surgically prepared for electrophysiological sleep-wake recording and
      simultaneous bilateral microinjections into PPT. 200nl of prazosin (alpha1
      antagonist) or clonidine (alpha2-agonist) or propranolol (beta-antagonist) or
      combination of picrotoxin (GABA-A antagonist) and clonidine or vehicle (control)
      was microinjected bilaterally into PPT using a remote-controlled pump and the
      effects on REM sleep compared. Prazosin, clonidine and propranolol increased the
      total time spent in REM sleep whereas co-injection of picrotoxin and clonidine
      did not affect REM sleep. The results suggest that NA in PPT tonically inhibits
      REM sleep, possibly by acting on the cholinergic REM-ON neurons, while GABA
      inhibits the release of NA for REM sleep regulation. A model of neural
      connections explaining such regulation has been presented.

PMID- 16616215
TI  - Factors predictive of early or late aneurysm sac size change following
      endovascular repair.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      aneurysm sac size change at 1, 6, 12, and 24 months and a set of 10 independent
      "predictive" variables by using a general linear model analysis. METHODS: In a
      multicenter trial, 351 patients received the Zenith tri-modular bifurcated
      endograft. The predictive variables used for this analysis were endoleak by type,
      age, gender, smoking status, and the preprocedure variables of maximum aneurysm
      major diameter, minor neck diameter, proximal neck length, neck plaque/thrombus,
      and neck shape; and patent inferior mesenteric artery at predischarge. The
      aneurysm change was calculated as the difference from the predischarge (< or = 7
      days of implant) maximum aneurysm major diameter measurement to the maximum
      aneurysm major diameter measurement at follow-up examination periods of 1, 6, 12,
      and 24 months. The same 10 predictive variables were used to assess the absolute
      change in maximum aneurysm minor diameter and aneurysm area. Additionally, the
      percent change from predischarge was also assessed for the major diameter, minor
      diameter, and aneurysm area. RESULTS: None of the independent variables were
      predictive of absolute sac size change or percent change at 1 month. At 6 months,
      the presence of an endoleak (P < .01) and preprocedure neck thrombus/plaque (P =
      .01) were significant predictors of absolute and relative aneurysm size change
      for all measurements (major diameter, minor diameter, and area) and were more
      likely to be associated with less sac shrinkage or to have sac growth.
      Additionally, preoperative maximum aneurysm major diameter was a significant
      predictor for absolute change in area (P < .01). Larger preprocedure aneurysm
      diameters were more likely to experience more shrinkage. The significant
      predictors of size change at 12 months included preprocedure maximum aneurysm
      major diameter, the presence of endoleak at 12 months, preoperative neck
      thrombus/plaque, and gender. At 24 months, significant predictors of aneurysm
      size change included preprocedure maximum aneurysm major diameter, endoleak at 24
      months, and preprocedure neck thrombus/plaque. When the longitudinal model was
      used, the presence of an endoleak, thrombus/plaque within the proximal neck at
      preprocedure, and preprocedure maximum aneurysm major diameter were found to be
      significantly related to the size of the maximum aneurysm major diameter over
      time. CONCLUSIONS: This study supports the concept that early and late sac size
      change following EVAR is influenced by identifiable independent predictive
      variables.

PMID- 16616216
TI  - Are type II endoleaks after endovascular aneurysm repair endograft dependent?
AB  - PURPOSE: Most clinical end points after endovascular aneurysm repair (EVAR) are
      endograft-specific, but type II endoleaks have been assumed to be an unavoidable
      consequence of the repair method and independent of the type of endograft used.
      Some recent data have suggested that the rate of type II endoleaks may also be
      graft-dependent. We reviewed a large clinical experience with six endografts to
      determine the behavior of type II endoleaks and whether they are graft-specific.
      METHODS: All elective EVAR cases from five university institutions from 1996 to
      2003 were retrospectively analyzed. Endografts used in <50 patients were
      excluded. Endoleaks were diagnosed and classified from contrast-enhanced computed
      tomography (CT) scans by the treating surgeons. Results of angiography and
      interventions for endoleaks were tracked. The rate of type II endoleaks was
      compared among endografts at 1, 6, and 12 months, and yearly thereafter.
      Statistical significance was defined as P < .05. RESULTS: During the study
      period, 1909 patients underwent elective EVAR and had an adequate imaging follow
      up at one of the specified time points. At 1 month, the overall rate of type II
      endoleak was 14.0% (range, 9.8% to 25.2%.) The Excluder had a significantly
      higher incidence of type II endoleaks at 1 month but was similar to most other
      grafts during longer follow-up. At 6 months, the overall rate of type II endoleak
      was 16.3% (range, 8.3% to 16.8%). The Talent and Lifepath had an apparent lower
      initial rate of type II leaks, but this was only significant for the Talent at 6
      months compared with Excluder, Zenith, and Ancure, and at 1 year compared with
      Excluder and Zenith. No graft had a long-term statistically significant
      difference in the rate of type II endoleak formation. Intervention rates varied
      by institution and graft type but in general were quite low. Of 25 successful
      interventions (Ancure, 12; AneuRx, 8; Excluder, 2; Lifepath, 2; Zenith, 1;
      Talent, 0), 21 were performed during the first year. Interim spontaneous
      resolution, defined as a negative CT scan after a CT positive for endoleak, was
      high, especially in the first year. Resolution of type II endoleaks occurred in
      54 (33%) of 164 between 1 and 6 months, in 37 (33%) of 112 between 6 and 12
      months, in 20 (35%) of 57 from 12 to 24 months, and in 5 (20%) of 25 between 24
      and 36 months. The various grafts had a nearly identical pattern, but the rates
      were highest for the Talent. Late appearing endoleaks, defined as a positive CT
      after a negative CT, were frequent. At 6 months, 44 (30%) of 147 type II
      endoleaks were newly diagnosed. The rates were 37 (35%) of 107 at 12 months, 15
      (27%) of 56 at 2 years and 5 (25%) of 20 at 3 years. No conversions to open
      repair for type II endoleaks were noted in the first 4 years. The thrombus burden
      could not be determined in this analysis. CONCLUSIONS: Type II endoleaks occur in
      nearly 15% of patients treated by EVAR. The early incidence varies only slightly
      with graft type. The long-term prevalence and clinical significance are masked by
      different treatment patterns, spontaneous resolution, newly evident endoleaks,
      and aneurysm size at initial treatment.

PMID- 16616217
TI  - Adjunctive primary stenting of Zenith endograft limbs during endovascular
      abdominal aortic aneurysm repair: implications for limb patency.
AB  - OBJECTIVE: Endograft limb occlusion is an infrequent but serious complication of
      endovascular abdominal aortic aneurysm (AAA) repair. The insertion of additional
      stents within the endograft limb may prevent future occlusion. This study
      evaluates limb patency with and without adjunctive stenting of endograft limbs at
      the time of endovascular AAA repair. METHODS: We performed a retrospective review
      of 248 patients who underwent endovascular abdominal aortic aneurysm repair with
      the Zenith AAA endovascular graft between 1999 and 2004. Among these patients,
      two groups were identified: 64 patients with adjunctive stents placed in 85 limbs
      and 184 patients without additional bare stent placement in endograft limbs at
      the time of endovascular AAA repair. RESULTS: Women comprised 23% of stented and
      11% of unstented patients (P = .02). The mean length of follow-up in the stented
      and unstented groups was 2.0 years. There were 13 instances of limb thrombosis in
      13 patients (5.2% of patients, 2.7% of limbs), all in the unstented group. No
      limb occlusions occurred in the presence of adjunctive bare metal stents. Seventy
      three percent of the occlusions occurred < or = 6 months of endovascular AAA
      repair. Two patients (15%) had no symptoms of lower-extremity ischemia despite
      graft limb occlusion and did not undergo intervention. The others underwent
      thrombectomy (n = 2), thrombectomy with bare stent placement (n = 3), femoral
      femoral bypass (n = 4), thrombolysis (n = 1), and thrombolysis with bare stent
      placement (n = 1). Of the seven who underwent thrombectomy or thrombolysis, three
      had no additional stents placed at the secondary procedure, and two of these
      three went on to rethrombose. By life-table analysis, primary patency at 3 years
      in the stented and nonstented limbs was 100% +/- 0% and 94% +/- 3%, respectively
      (P = .05). CONCLUSIONS: The intraoperative insertion of additional bare metal
      stents appeared to eliminate the risk of thrombosis and was without complication.
      Of the 85 stented limbs in this series, not one occluded. The overall rate of
      limb thrombosis was low, with most limb occlusions occurring < or = 6 months of
      stent-graft insertion, and would probably have been even lower had we been able
      to identify all high-risk cases for prophylactic adjunctive stenting. Limb
      occlusion denotes an underlying problem with the graft, which if left untreated
      after thrombectomy or thrombolysis will lead to rethrombosis. Postoperative
      imaging was of little value in detecting impending limb occlusion. Based on these
      findings, we believe one should identify and stent any limbs that appear to be at
      risk for thrombosis, but this study lacks the data to predict which limbs need
      stenting.

PMID- 16616218
TI  - Consistency in endovascular aneurysm repair suitability assessment requires group
      decision audit.
AB  - INTRODUCTION: Proper selection of patient and stent-graft combinations in
      endovascular aneurysm repair (EVAR) depends on knowledge and experience with the
      different types of stents that have to be adapted to the patient's unique
      abdominal aortoiliac anatomy. The aim of this study was to analyze the
      consistency and variance in EVAR suitability assessment between clinicians.
      METHODS: Worksheets that contained anatomic data derived from computed tomography
      scans and angiography were compiled for 202 patients. Five clinicians, all
      experienced in EVAR surgery, assessed the anatomic data on the worksheets for
      suitability for three types of stent-grafts. The obtained 3030 assessments
      represented a quantification of the likelihood of success the clinician expected
      for effective and durable sealing and fixation of the stent-graft in EVAR. The
      Delphi method was used to determine consensus in the thinking process among
      clinicians, and kappa analysis was used to determine the proportion of variances
      in the assessment result between clinicians. RESULTS: With the Delphi method,
      Cronbach alpha values of 0.87, 0.87, and 0.90 were reached for the three types of
      stent-grafts in the second assessment round. The individual clinician-group
      correlation in round two was between 0.69 and 0.86 for clinicians 1, 2, 3, and 4.
      Between clinician 5 and the others, correlation varied between 0.43 and 0.64. The
      kappa values ranged between 0.32 and 0.51 among clinicians 1, 2, and 3. Between
      clinician 5 and the others, kappa values between 0.08 and 0.29 were reached.
      CONCLUSION: EVAR suitability estimation in a cohort of patients is highly
      consistent in a group of experienced clinicians. The EVAR suitability estimation
      at the individual patient level varies substantially between clinicians, however.
      Aggregating expert opinions in abdominal aortic aneurysm anatomic suitability
      assessment for EVAR had the opportunity to replace individual clinician decision
      diversification in a more solid and consistent group decision process.

PMID- 16616219
TI  - Early outcomes after elective and emergent endovascular repair of the thoracic
      aorta.
AB  - BACKGROUND: Endovascular treatment of thoracic aortic pathology has emerged as a
      viable alternative to open surgical repair in both the elective and emergent
      settings. The aim of this study was to evaluate preoperative work-up, intra
      operative strategy, and outcomes of endovascular stent-grafting of the thoracic
      aorta in patients undergoing elective repair and those undergoing emergent
      repair. METHODS: All patient information was obtained by a retrospective review
      of an established clinical database for all endovascular thoracic stent-graft
      cases. From October 1999 to August 2005, 70 patients were treated with
      endovascular stent-grafts for lesions of the thoracic aorta. Thirty-five patients
      had an elective endovascular procedure, and 35 patients had an emergent
      procedure. RESULTS: Thirty-five patients in the endovascular (EL) group were
      treated for aneurysm (n = 34) and type B dissection (n = 1). Thirty-five patients
      in the emergent (EM) group were treated for aneurysm (n = 10), intramural
      hematoma (n = 10), type B dissection (n = 7), traumatic rupture (n = 7), and
      aortoesophageal fistula (n = 1). Preoperative angiography was performed in 94.3%
      (33/35) of EL patients but in only 45.7% (16/35) EM patients (P < .005). The EM
      procedures had significantly shorter operative times, used lower contrast
      volumes, used fewer stent-graft components (mode 2, range 1 to 5 vs mode 1, range
      1 to 3; P = .02), and spinal cerebrospinal fluid drains were used significantly
      less often (82.9% vs 57.1%, P = .04). Both groups had similar 30-day morbidity,
      mortality (0/35 EL vs 1/35 [2.9%] EM, P = .99), postoperative endoleak (9/35
      [25.7%] EL vs 7/35 [20.0%] EM, P = .78), endovascular failure (3/35 [8.6%] EL vs
      5/35 [14.3%] EM, P = .71), and patient survival. CONCLUSION: There are
      significant differences in the underlying pathology, preoperative evaluation, and
      operative course between elective and emergency treatment endovascular procedures
      for lesions of the thoracic aorta. Endovascular repair of thoracic aortic lesions
      can be accomplished with low perioperative mortality and morbidity rates, as well
      as acceptable endoleak and endovascular failure rates for both elective and
      emergency procedures.

PMID- 16616220
TI  - Timing of endovascular repair of blunt traumatic thoracic aortic transections.
AB  - BACKGROUND: Patients with blunt traumatic thoracic aortic transection (BTTAT)
      just distal to the takeoff of the left subclavian artery typically have
      concomitant injuries that make open emergent surgical repair highly risky. Over
      the past decade, endovascular repair of the injured thoracic aorta with
      commercially available and custom-made covered stents has developed as a viable
      option, with reported decreases in short-term morbidity and mortality. If active
      extravasation of contrast from the injured thoracic aorta is not appreciated on
      chest computed tomography scan, other concurrent injuries of the head, abdomen,
      and extremities can often be repaired with careful control of blood pressure. The
      timing of endovascular repair of the traumatic thoracic aortic transection,
      however, often comes into question, particularly with the presence of fever,
      pneumonia, or bacteremia. We sought to identify a time frame during which
      endovascular repair of BTTAT could safely be performed. METHODS: Age, concomitant
      injuries, time from trauma to repair, type of device, and major outcomes were
      recorded. RESULTS: Over a 5-year period (January 2000 to March 2005), 51 patients
      presented with BTTAT. Twenty-seven (52.9%) patients with BTTAT died shortly after
      arrival. Of the remaining 24, 9 underwent emergent open repair, with 1
      intraoperative death. Two delayed open repairs were performed. Thirteen patients
      with BTTAT underwent delayed endovascular repair. Successful endovascular repair
      of BTTAT was performed in all 13 patients, with no intraoperative deaths. Seven
      patients were treated with commercial devices and six with custom-made covered
      stents. None of the repairs was performed emergently. The timing of repair ranged
      from 1 day to 7 months (median, 6 days), and all patients were treated
      aggressively with beta-blockade before surgery. One patient was discharged from
      the hospital and underwent elective repair at a later date. Three patients died
      in the postoperative period (30 days): two from multisystem organ failure and one
      from iliac artery complications encountered at the time of device deployment. The
      remaining 10 patients were successfully discharged to a rehabilitation facility.
      CONCLUSIONS: The opportunity to successfully perform endovascular repair of BTTAT
      may be possible many days after the initial injury in the hemodynamically stable
      trauma patient.

PMID- 16616221
TI  - Replanting the inferior mesentery artery during infrarenal aortic aneurysm
      repair: influence on postoperative colon ischemia.
AB  - BACKGROUND: Replanting the inferior mesentery artery (IMA) to prevent ischemic
      colitis (IC) has been discussed for many years; yet, to our knowledge, no
      prospective studies have been conducted to compare the incidence of
      histologically proven IC in patients with and without IMA revascularization. The
      aim of this prospective study, with histologic evaluation of the sigmoid colon
      mucosa, was to assess the influence of replanting the IMA on IC and mortality.
      METHODS: From January 1999 to December 2003, 160 consecutive patients who were
      operated on for a symptomatic (n = 21) or asymptomatic (n = 139) infrarenal
      aortic aneurysm were prospectively assessed and randomly assigned either to
      replanting or ligating the IMA. Sigmoidoscopy with biopsy was performed on day 4
      or 5 after surgery; an autopsy was performed on patients not surviving to day 5
      after surgery. All patients gave written informed consent. RESULTS: Of the 160
      randomized patients, 128 had a confirmed patent IMA and formed the basis of this
      study. Their age was 70 +/- 8 years (men, 70 +/- 8 years; women, 73 +/- 7 years).
      The IMA was replanted in 67 patients (52%) and ligated in 61 (48%)
      intraoperatively. IC developed in six patients with a replanted IMA and in 10
      with a ligated IMA (relative risk [RR], 0.55; 95% confidence interval [CI], 0.21
      to 1.41; chi2 = 1.62; P = .203). Blood loss in the two cohorts did not differ
      significantly (P = .788); however, patients with IC had a significantly higher
      blood loss compared with the cohort without IC (P = .012) and were older (P =
      .017). Age, sex distribution, clamping time, the use of tube or bifurcated
      grafts, and intraoperative hypotension did not differ between patients with
      ligated or replanted IMA. CONCLUSION: Although replanting the IMA did not confer
      a statistically significant reduction of perioperative morbidity or mortality in
      this study, it appears that older patients and patients with increased
      intraoperative blood loss might benefit from IMA replantation, because this
      maneuver does not increase perioperative morbidity or substantially increase
      operation time.

PMID- 16616222
TI  - Laparoscopy-assisted abdominal aortic aneurysm repair: early and middle-term
      results of a consecutive series of 122 cases.
AB  - BACKGROUND: Endoaneurysmorrhaphy with intraluminal graft placement, described by
      Creech, is the gold standard for abdominal aortic aneurysm (AAA) repair.
      Endovascular aneurysm repair has gained popularity for its minimal invasiveness
      and satisfying short-term results, but there are still many concerns about the
      long-term success of the procedure. Since 1998, laparoscopic surgery has been
      proposed for AAA treatment. The potential benefits of a minimally invasive
      procedure reproducing the endoaneurysmorrhaphy results over time have been
      advocated. In our experience, hand-assisted laparoscopic surgery (HALS) has been
      routinely used for the open-surgery transperitoneal/retroperitoneal approach and
      for endovascular aneurysm repair. After 4 years, we are able to define the early
      and middle-term results of such laparoscopic-assisted treatment. METHODS: From
      October 2000 to March 2004, 604 consecutive nonurgent AAAs were treated at our
      institution. Of these, 122 (20.2%) were treated by HALS. Exclusion criteria for
      HALS were hostile abdomen (previous major abdominal or aortic surgery), bilateral
      diffuse common iliac and/or hypogastric aneurysms, massive aortoiliac
      calcifications, and severe cardiac (ejection fraction <35%) and respiratory
      (P(O2) <60 mm Hg or carbon dioxide >50 mm Hg) insufficiency. Juxtarenal and
      proximal iliac aneurysms were not a contraindication, nor was obesity. In all
      patients, we performed a minilaparotomy (7-8 cm) both for laparoscopic hand
      assisted dissection and for endoaneurysmorrhaphy. All perioperative data were
      prospectively recorded. Follow-up consisted of ultrasonography and clinical
      evaluation after 6 and 12 months and then every year after surgery. RESULTS: The
      mean laparoscopic and total operative times were respectively 64 +/- 32 minutes
      and 257 +/- 70 minutes, the mean aortic cross-clamping time was 76 +/- 26
      minutes, and the mean autotransfused blood volume was 1136 +/- 711 mL. The
      overall mortality and morbidity were respectively 0% and 12.2%. Morbidity was
      surgery related in only two cases (bleeding from an ipogastric artery lesion and
      a leg graft thrombosis). The mean intensive care unit stay was 14.3 +/- 13 hours.
      Oral food intake was resumed after 27.4 +/- 15 hours, and patients were
      discharged after a mean of 4.4 +/- 1.7 days. Operative times were not affected by
      obesity, suprarenal aortic cross-clamping, or aneurysm size. Both concomitant
      iliac aneurysms and bifurcated graft implantation (related to longer vascular
      reconstruction) involved significantly longer operative times. The learning curve
      of the procedure (comparing the first 30 patients with the last 92 patients) led
      to significantly shorter endoscopic, cross-clamping, and total operative times (P
      = .000). The mean follow-up was 28.6 +/- 16 months. Three incisional hernias and
      one case of bowel occlusion were detected. All these cases (3.4%) required
      laparoscopic treatment. CONCLUSIONS: The HALS technique is a safe and minimally
      invasive treatment for AAA; it is useful for limiting the need for conventional
      open surgery and reducing the length of hospital stay. Despite the lack of
      randomized studies, HALS seems to be associated with a better postoperative
      course than standard open surgery. HALS can also be considered as an equivalent
      of a well-established procedure and as a bridge between open and total
      laparoscopic surgery.

PMID- 16616223
TI  - Late reintervention for aortic graft-related events and new aortoiliac disease
      after open abdominal aortic aneurysm repair in an Australian population.
AB  - OBJECTIVE: To examine late reintervention rates for aortic graft-related events
      and new aortoiliac disease after open abdominal aortic aneurysm (AAA) repair in
      an Australian population. METHODS: Interrogation of a prospective computerized
      database identified 1256 consecutive patients (1058 men, 198 women; median age,
      70 years; range, 40 to 97 years) who survived open repair of nonruptured (n =
      957, group I) and ruptured (n = 299, group II) infrarenal AAA in a single
      institution between January 1, 1982 and December 31, 2003. Median (range) follow
      up was 41 (1 to 261) months for group I and 30 (1 to 243) months for group II.
      RESULTS: In group I, 33 patients (3.4%) underwent 38 late reinterventions: 20
      patients (2.1%) for aortic graft-related events at a median (range) interval of
      36 (1 to 94) months after the index AAA repair, with a 30-day mortality rate of
      15%; and 13 patients (1.4%) for new aortoiliac disease at a median (range)
      interval of 33 (3 to 207) months, with 30-day mortality of 8%. In group II, 15
      patients (5%) underwent 16 late reinterventions: 10 patients (3.3%) for aortic
      graft-related events at a median (range) interval of 5 (2 to 112) months, with a
      30-day mortality of 10%; and five patients (1.7%) for new aortoiliac disease at a
      median (range) interval of 67 (39-105) months, with a 30-day mortality of 40%.
      There was no significant difference in the late reintervention rate between the
      groups: group I, 33 (3.4%) of 957 vs group II, 15 (5%) of 299 (P = .23). For all
      patients, the estimated survival at 1, 3, 5 and 10-years was 90%, 79.4%, 66.4%,
      and 31.6%, respectively; estimated survival free from reintervention at 1, 3, 5
      and 10-years was 98.7%, 97.1%, 95.1%, and 91.9%, respectively. CONCLUSIONS: These
      data demonstrate, for the first time, that open AAA repair has excellent long
      term durability in an Australian population and the results compare favorably
      with previous reports from North America and Europe. These data represent an
      important benchmark for comparison of the results of endovascular AAA repair in
      this patient population.

PMID- 16616225
TI  - Internal thoracic artery-inferior epigastric artery as a collateral pathway in
      aortoiliac occlusive disease.
AB  - OBJECTIVE: In patients with aortoiliac occlusion, the internal thoracic artery
      inferior epigastric artery (ITA-IEA) collateral is one of the collaterals
      supplying blood flow to the lower extremity, and the interruption of this
      collateral may cause severe leg ischemia. The aim of this study was to evaluate
      by color duplex ultrasonography scans the ITA-IEA pathway and its significance as
      a collateral in providing lower-extremity perfusion in aortoiliac occlusive
      disease. METHODS: Color duplex ultrasonography scans were prospectively performed
      in 64 consecutive patients with aortoiliac occlusion. Blood flow measurement in
      the ITA, IEA, and common femoral artery was done on both sides. The patients were
      stratified according to occlusion level (aorta, common iliac artery, external
      iliac artery), and the data obtained from such groups were compared. RESULTS: In
      95% of patients with aortoiliac occlusion, the ITA-IEA pathway was functioning as
      a collateral, with mean collateral flow of 66 +/- 48 mL/min, and its average
      contribution to lower-extremity perfusion was 38% +/- 23%. Additionally, a
      moderately positive correlation was found between flows of ITA and IEA (r = 0.55,
      P < .0001). Depending on the level of occlusion, the collateral flow and its
      contribution to perfusion progressively decreased from the proximal to distal
      aortoiliac occlusion level. Furthermore, the difference in the ITA-IEA flow
      volume was statistically significant between occlusion levels (P = .009), but the
      differences in the perfusion contribution were not different among levels (P =
      .311). There was also no statistical difference between the groups concerning
      collateral flow volume and contribution to lower-extremity perfusion in relation
      to unilateral or bilateral occlusion of the iliac artery, the state of distal run
      off being good or poor, or the clinical findings being mild or severe.
      CONCLUSION: In patients with aortoiliac occlusion, the ITA-IEA collateral pathway
      is an important route providing lower-extremity perfusion. Additionally, Doppler
      sonographic flow measurements of the contribution of the ITA-IEA route to lower
      extremity perfusion may provide beneficial diagnostic information necessary for
      the pretreatment work-up of patients with aortoiliac occlusion, especially for
      whom the ITA is planned to be used as a coronary artery graft.

PMID- 16616226
TI  - Analysis of parameters associated with hypotension requiring vasopressor support
      after carotid angioplasty and stenting.
AB  - INTRODUCTION: Systemic hypotension has been observed for up to 36 hours in
      response to stimulation of the carotid baroreceptor by carotid angioplasty and
      stenting (CAS). The aim of this study was to identify risk factors and cardiac
      outcomes for postprocedural hypotension requiring vasopressor support after CAS.
      METHODS: Between 2003 and 2005, 143 patients (87 men; mean age, 75 years) with
      high-grade carotid artery stenosis (mean, 87.3%) were treated with CAS and
      prospectively entered into a vascular registry. Data were retrospectively
      analyzed to determine factors predictive of hypotension requiring vasopressor
      support after CAS. Atropine and appropriate intravenous crystalloid solution were
      administered during CAS. For the first 30 patients, atropine was only used for
      symptomatic patients but then became routine and was used for all patients with
      primary carotid stenosis. Hypotension (systolic blood pressure <90 mm Hg or a
      mean arterial blood pressure <50 mm Hg) unresponsive to conservative measures was
      treated with vasopressors (phenylephrine or norepinephrine). Patients were
      stratified into three groups based on hypotension requiring vasopressors: (1) no
      vasopressors, (2) vasopressors for < or = 24 hours (short duration), and (3)
      vasopressors for >24 hours (prolonged duration). Risk factors for hypotension
      requiring vasopressors were analyzed by univariate and multivariate logistic
      regression analysis. RESULTS: Postprocedural hypotension requiring vasopressor
      treatment was seen in 16 (11%) of 143 of patients, with 6 (4%) requiring
      vasopressor support for >24 hours. Mean duration of vasopressor administration
      for all patients was 17 +/- 10 hours (range, 6 to 36 hours). By univariate
      analysis, a history of a previous myocardial infarction (P = .02) or use of the
      PercuSurge occlusion balloon (P = .05) were both associated with increased
      incidence of short duration (</=24 hours) use of vasopressors, and female sex (P
      = .03) and age >80 years old (P = .02) were associated with prolonged (>24 hours)
      vasopressor requirement. On multivariate analysis adjusted for age and sex, a
      history of myocardial infarction (odds ratio [OR], 4.1; 95% confidence interval
      [CI], 1.0 to 16.4; P = .05) remained an independent predictor of short-duration
      vasopressors. On multivariate analysis, female sex (OR, 10.9; 95% CI, 1.2 to
      100.4; P = .04) and age >80 years old (OR, 13.8, 95% CI, 1.5 to 127.2; P = .02)
      remained independent predictors of prolonged vasopressor use. The incidence of
      periprocedural myocardial infarctions, arrhythmias, or congestive heart failure
      did not differ between those patients who did not receive vasopressors (5/127)
      and those who received vasopressors for a short (< or = 24 hours) duration (1/10,
      P = NS) or prolonged (>24 hours) duration (0/6, P = NS). CONCLUSION: Prolonged
      hypotension requiring vasopressor support occurs in a minority of patients after
      CAS, with higher incidences in older women. In contrast, hypotension requiring a
      more limited duration of vasopressor use occurs more commonly in patients who had
      a prior myocardial infarction, independent of age or sex. In this cohort of
      patients, vasopressors required for hypotension were not associated with an
      increased incidence of periprocedural cardiac complications. Despite the
      increased incidence of prolonged hypotension in older women, this study
      demonstrates that CAS can be performed without an increase in cardiac morbidity
      in older women.

PMID- 16616227
TI  - Vocal cord paralysis after aortic arch surgery: predictors and clinical outcome.
AB  - OBJECTIVE: This study is retrospective cohort study of data on vocal cord
      paralysis after aortic arch surgery collected during 14 years at a general
      hospital. We investigated factors in the development of vocal cord paralysis
      after aortic arch surgery and the effect of vocal cord paralysis on clinical
      course and outcome. METHODS: We reviewed data for 182 patients who underwent
      aortic arch surgery for aortic arch aneurysm and aortic dissection between 1989
      and 2003, of whom 58 patients had proximal aortic repair, 62 had distal arch
      repair, and 62 had total arch repair. We assessed factors associated with the
      development of vocal cord paralysis and examined in detail the clinical outcome
      of patients with vocal cord paralysis. RESULTS: Postoperative vocal cord
      paralysis occurred in 40 patients. Multiple logistic regression analysis revealed
      the following risk factors with odds ratios (OR) for vocal cord paralysis:
      extension of procedures into distal arch (OR, 17.0), chronic dilatation of the
      aorta at the left subclavian artery (OR, 9.14), and total arch repair (OR, 4.24).
      Adoption of open-style stent-grafts reduced the incidence of vocal cord paralysis
      (OR, 0.031). The postoperative occurrence of vocal cord paralysis itself emerges
      as an independent predictor of pulmonary complications (OR, 4.12) and leads to a
      longer duration of hospital stay. CONCLUSIONS: The risk of vocal cord paralysis
      after aortic arch surgery depends on surgical factors, such as aneurysmal
      involvement of the distal arch, or the application of newer, less invasive
      surgical procedures. Vocal cord paralysis after aortic arch surgery itself, under
      aggressive postoperative respiratory management, did not increase aspiration
      pneumonia but was associated with postoperative complications leading to higher
      hospital mortality and prolonged hospitalization.

PMID- 16616228
TI  - Flow measurement before and after papaverine injection in above-knee prosthetic
      femoropopliteal bypass.
AB  - OBJECTIVE: To investigate the value of intraoperative blood flow measurements on
      early and long-term patency of above-knee prosthetic femoropopliteal bypass.
      METHODS: Flow was measured with a transit time flowmeter before (basal flow) and
      after an intragraft injection of papaverine (papaverine flow) in 87 operations
      (86 patients) between January 1990 and December 2001. Sixty-one grafts were of
      polyester, and 26 were of polytetrafluoroethylene. The operations were done under
      epidural anesthesia. The preoperative angiographic run-off score and clinical
      risk factors were recorded. Patency rates were analyzed with the product limit
      method and compared with the log-rank test. Variables found to be near
      significantly related to patency rates (P < .1) were included in a multivariate
      analysis performed with the Cox proportional hazard model. RESULTS: Basal flow
      measurements were not related to patency. The 2- and 5-year patency rates for
      grafts with a papaverine flow < or = 500 mL/min were 48% and 18% compared with
      66% and 52% for grafts with a papaverine flow > or = 500 mL/min. These
      differences were statistically significant (P = .012, hazard ratio, 2.6). Two-
      and 5-year patency rates for smokers vs nonsmokers were 44% and 18% vs 69% and
      54%. The patency rates for patients with poor vs good run-off were 42% and 27% vs
      66% and 31%. Smoking (P = .008, hazard ratio, 2.75) and poor run-off score (P =
      .009, hazard ratio, 2.38) were found to be independent risk factors for reduced
      patency rates. Poor run-off score did not correlate with low values of measured
      basal or papaverine flow. CONCLUSIONS: Papaverine flow of < or = 500 mL/min is
      associated with reduced mid- and long-term patency rates. Additional
      antithrombotic medication and frequent follow-up for these grafts should be
      considered. The inferior patency rates of smokers and patients with poor run-off
      indicate that prosthetic bypass is less suitable for these groups of patients.

PMID- 16616229
TI  - Revascularization for peripheral vascular disease in Aboriginal and non
      Aboriginal patients.
AB  - BACKGROUND: Canadian Aboriginal subjects have a higher prevalence of diabetes,
      renal disease, and lower extremity amputation than non-Aboriginal subjects.
      However, limited information is available about patient outcomes for arterial
      bypass surgery in Canadian Aboriginal compared with non-Aboriginal subjects.
      METHODS: A retrospective study of all patients undergoing revascularization for
      peripheral vascular disease at a tertiary care referral center was performed.
      RESULTS: A total of 828 procedures were performed on 678 patients between 1995
      and 2002: 108 (13%) procedures on 84 (12%) Aboriginal patients and 720 (87%)
      procedures on 594 (88%) non-Aboriginal patients. Aboriginal patients had a higher
      prevalence of diabetes, chronic renal failure, and end-stage renal disease than
      non-Aboriginal patients. Aboriginal patients presented with more serious
      complications (gangrene [Aboriginal, 63 [58%] of 108 patients; non-Aboriginal,
      112 [16%] of 720 patients; P < .0001] and nonhealing ulcer [Aboriginal, 29 [27%]
      of 108 patients; non-Aboriginal, 131 [18%] of 720 patients; P < .05]) and
      required urgent or emergency revascularization (Aboriginal, 47 [49%] of 95
      patients; non-Aboriginal, 228 [36%] of 634 patients; P < .02) more frequently
      than non-Aboriginal patients. The 60-month patient mortality was similar for both
      groups (Aboriginal, 20 [24%] of 84 patients; non-Aboriginal, 160 [27%] of 594
      patients; not significant), but Aboriginal patients had loss of limb more
      frequently (Aboriginal, 19 [18%] of 108 patients; non-Aboriginal, 62 [9%] of 720
      patients; P < .0001) and had loss of primary graft patency more frequently
      (Aboriginal, 39 [36%] of 108 patients; non-Aboriginal, 155 [22%] of 720 patients;
      P < .0001) than non-Aboriginal patients. CONCLUSIONS: Canadian Aboriginal
      subjects had worse outcomes with revascularization than non-Aboriginal subjects,
      but ethnicity and diabetes were not independent risk factors for poor outcome.
      Multivariate analysis showed that the poor outcomes in mortality, limb salvage,
      and primary graft patency among Aboriginal patients undergoing revascularization
      may be attributed to renal disease and a more advanced mode of presentation of
      peripheral vascular disease complications at the time of intervention.

PMID- 16616230
TI  - Results of PREVENT III: a multicenter, randomized trial of edifoligide for the
      prevention of vein graft failure in lower extremity bypass surgery.
AB  - OBJECTIVE: The PREVENT III study was a prospective, randomized, double-blinded,
      multicenter phase III trial of a novel molecular therapy (edifoligide; E2F decoy)
      for the prevention of vein graft failure in patients undergoing infrainguinal
      revascularization for critical limb ischemia (CLI). METHODS: From November 2001
      through October 2003, 1404 patients with CLI were randomized to a single
      intraoperative ex vivo vein graft treatment with edifoligide or placebo. After
      surgery, patients underwent graft surveillance by duplex ultrasonography and were
      followed up for index graft and limb end points to 1 year. A blinded Clinical
      Events Classification committee reviewed all index graft end points. The primary
      study end point was the time to nontechnical index graft reintervention or major
      amputation due to index graft failure. Secondary end points included all-cause
      graft failure, clinically significant graft stenosis (>70% by angiography or
      severe stenosis by ultrasonography), amputation/reintervention-free survival, and
      nontechnical primary graft patency. Event rates were based on Kaplan-Meier
      estimates. Time-to-event end points were compared by using the log-rank test.
      RESULTS: Demographics, comorbidities, and procedural details reflected a
      population with CLI and diffuse atherosclerosis. Tissue loss was the presenting
      symptom in 75% of patients. High-risk conduits were used in 24% of cases,
      including an alternative vein in 20% (15% spliced vein and 5% non-great saphenous
      vein) and 6% less than 3 mm in diameter; 14% of the cases were reoperative bypass
      grafts. Most (65%) grafts were placed to infrapopliteal targets. Perioperative
      (30-day) mortality occurred in 2.7% of patients. Major morbidity included
      myocardial infarction in 4.7% and early graft occlusion in 5.2% of patients. Ex
      vivo treatment with edifoligide was well tolerated. There was no significant
      difference between the treatment groups in the primary or secondary trial end
      points, primary graft patency, or limb salvage. A statistically significant
      improvement was observed in secondary graft patency (estimated Kaplan-Meier rates
      were 83% edifoligide and 78% placebo; P = .016) within 1 year. The reduction in
      secondary patency events was manifest within 30 days of surgery (the relative
      risk for a 30-day event for edifoligide was 0.45; 95% confidence interval, 0.27
      0.76; P = .005). For the overall cohort at 1 year, the estimated Kaplan-Meier
      rate for survival was 84%, that for primary patency was 61%, that for primary
      assisted patency was 77%, that for secondary patency was 80%, and that for limb
      salvage was 88%. CONCLUSIONS: In this prospective, randomized, placebo-controlled
      clinical trial, ex vivo treatment of lower extremity vein grafts with edifoligide
      did not confer protection from reintervention for graft failure.

PMID- 16616232
TI  - Parenteral therapy with lipo-ecraprost, a lipid-based formulation of a PGE1
      analog, does not alter six-month outcomes in patients with critical leg ischemia.
AB  - PURPOSE: Eicosanoids with vasodilating and angiogenic properties have been
      postulated to be effective therapies for critical leg ischemia (CLI) secondary to
      atherosclerotic peripheral arterial disease. The ability to deliver active drug
      to the site of action at adequate doses for sufficient duration has been a major
      limitation in the clinical development of such therapies. Lipo-ecraprost is a
      lipid-encapsulated prostaglandin E1 prodrug with the potential to deliver active
      prostaglandin to the site of critical arterial ischemia. The current trial was
      designed to test the hypothesis that lipo-ecraprost would improve amputation-free
      survival in patients with CLI who had no revascularization options. METHODS: The
      study was randomized, multicenter, double blind, and placebo controlled. Patients
      who met clinical and hemodynamic criteria were randomized to receive placebo or
      lipo-ecraprost (60 microg) administered intravenously on each of 5 days per week,
      for a total of 8 weeks. The study's primary endpoint was the rate of a composite
      end point of death or amputation above the level of the ankle at 180 days (6
      months). RESULTS: The study was terminated on a recommendation from the Data and
      Safety Monitoring Board after the completion of a protocol-specified interim
      analysis for futility. At the time of termination, 383 of the planned 560
      patients had been randomized, of which 379 received at least one dose of study
      medication and thus were included in the intention-to-treat population. Twenty
      three patients were lost to follow-up and were not available for 6-month
      assessments. At 6 months of follow-up, there were 23 amputations in the 177
      patients who received placebo, and 29 amputations in the 179 patients randomized
      to lipo-ecraprost. At 6 months, 10 deaths had occurred in the placebo group and
      18 deaths had occurred in the lipo-ecraprost arm. Changes in lower-extremity
      hemodynamics over the 6-month study period did not differ between the placebo and
      lipo-ecraprost treatment arms. CONCLUSION: Intensive treatment with lipo
      ecraprost failed to modify the 6-month amputation rate in patients with CLI who
      were not candidates for revascularization.

PMID- 16616233
TI  - Valsartan improves resting skin blood flow in type 2 diabetic patients and
      reduces poly(adenosine diphosphate-ribose) polymerase activation.
AB  - OBJECTIVE: To examine the effect of a 12-week daily treatment with 160 mg of
      valsartan, an angiotensin II receptor blocker, on the microcirculation and
      macrocirculation of type 2 diabetic patients (T2DM) and healthy subjects.
      METHODS: This was a prospective, randomized, double-blind, placebo-controlled
      crossover study. Thirteen T2DM with no severe complications and 13 healthy
      subjects completed the trial. RESULTS: Treatment with valsartan in T2DM improved
      the resting forearm skin blood flow and increased the resting brachial artery
      diameter but had no effects on arterial blood pressure, large vessel vascular
      reactivity, or carotid intima-media thickness. Resting skin blood flow increased
      by 60% (2%-90%; median and 25th-75th percentiles) during valsartan treatment and
      by only 2% (-22% to 27%) during placebo treatment (P < .05). No changes were
      observed in the nondiabetic subjects. Immunostaining studies of forearm skin
      biopsy samples from T2DM and healthy subjects showed that valsartan reduced
      poly(adenosine diphosphate-ribose) polymerase (PARP) activity in 50% (6/12) of
      the subjects. PARP activity remained unchanged in placebo-treated subjects (P <
      .02). In addition, valsartan treatment increased CD31 staining in 33% (4/12) of
      the subjects, whereas no change was noted in sequential skin biopsy samples of
      placebo-treated subjects (P = .057). Valsartan had no effect on the biochemical
      markers of endothelial cell activation and other cytokines, including CAMs,
      interleukin 6, tumor necrosis factor alpha, C-reactive protein, adiponectin, and
      plasma activator inhibitor 1. CONCLUSIONS: Valsartan increases the resting skin
      blood flow in T2DM, likely through reduction of PARP activity.

PMID- 16616237
TI  - Meeting AHA/ACC secondary prevention goals in a vascular surgery practice: an
      opportunity we cannot afford to miss.
AB  - OBJECTIVE: In an effort to reduce cardiovascular mortality, patients with
      atherosclerotic arterial disease should undergo risk factor modification
      according to the American Heart Association/American College of Cardiology
      (AHA/ACC) Secondary Prevention Guidelines (hereafter, Guideline). We assessed
      compliance with the Guideline in a group of patients seen in a vascular surgery
      practice. METHODS: We evaluated 200 consecutive patients with lower-extremity
      occlusive disease, cerebrovascular disease, or abdominal aortic aneurysm seen by
      a university-based vascular surgery practice. The subjects were patients who had
      been seen previously in our clinic (ESTABLISHED) and new referrals (NEW). Data
      pertinent to each of the nine AHA/ACC Guideline goals were collected from patient
      interviews, medication histories, and laboratory records. Compliance with each of
      the Guideline goals was evaluated. Differences in compliance between ESTABLISHED
      and NEW patient groups were also compared. We also recorded whether a patient had
      a previous endovascular or open surgical vascular intervention (EVENT or NO
      EVENT). Differences in compliance between the EVENT and NO EVENT groups were
      compared. RESULTS: Most patients did not achieve the secondary prevention goals
      recommended in the Guideline. Patients who had a prior vascular intervention
      (EVENT) were significantly more likely to achieve goals for low-density
      lipoprotein level (43% vs 23%), and for statin (71% vs 39%), beta-blocker (46% vs
      27%), angiotensin-converting enzyme inhibitor (53% vs. 35%), and antiplatelet
      agent (85% vs. 68%) use (P < .05). ESTABLISHED patients were significantly more
      likely than NEW patients to have a prior EVENT (87% vs 47%, P < .0005).
      ESTABLISHED patients were significantly more likely than NEW patients to achieve
      goals for low-density lipoprotein level, beta-blocker, and statin use; however,
      these differences were likely due to the higher proportion of EVENT patients in
      the ESTABLISHED group. CONCLUSION: Compliance with the Guideline is suboptimal in
      patients with atherosclerotic arterial disease. Secondary prevention goals were
      more often achieved in the EVENT patient group, suggesting that a vascular
      intervention may lead to increased patient and physician awareness and compliance
      with the Guideline. A targeted effort towards risk factor modification in
      patients with atherosclerotic arterial disease could improve compliance with the
      Guideline and reduce cardiovascular mortality.

PMID- 16616235
TI  - Prospective evaluation of the relationship between C-reactive protein, D-dimer
      and progression of peripheral arterial disease.
AB  - OBJECTIVE: Elevated levels of C-reactive protein (CRP) and D-dimer (DD) have been
      associated with the presence and progression of various forms of atherosclerotic
      disease, particularly coronary heart disease. We hypothesize that there is a
      relationship between elevated levels of baseline CRP and DD and progression of
      peripheral arterial disease (PAD) in patients with symptomatic PAD. The current
      study is a prospective evaluation of this hypothesis. METHODS: Between 1996 and
      2003, 384 subjects were enrolled in a National Institutes of Health-sponsored
      blinded, prospective trial evaluating the effects of multiple atherosclerotic
      risk factors on progression of symptomatic PAD. Baseline levels of CRP and D
      dimer were obtained in 332 subjects. Subjects were followed every 6 months with
      clinical history and exam, ankle-brachial pressure index (ABI), and carotid
      artery duplex scanning (CDS). The primary study end point was a composite of ABI
      progression, CDS progression, stroke, myocardial infarction, amputation, and
      death from cardiovascular disease. Secondary end points included each of the
      components of the primary end point. The relationship between time to the various
      endpoints and baseline CRP and DD levels was examined by life-table analysis and
      Cox proportional hazards analysis. RESULTS: Adequate baseline samples for CRP and
      DD were available in 332 subjects (mean age, 67 years; 57.8% men) with mean
      follow-up of 38.4 months (range, 1 to 99 months). Mean baseline levels (+/- SD)
      for CRP were 0.8 +/- 1.14 (range, 0.03 to 13.0), and mean DD levels were 227.4 +/
      303.3 (range, 1.9 to 2744.8). Progression, as defined by the primary end point,
      occurred in 48.5% of subjects. Subjects with elevated CRP (highest tertile) were
      no more likely to have any of the progression end points than those with the
      lowest values (lowest tertile) (P = NS, log-rank test, for all comparisons). By
      univariate analysis, subjects with elevated DD (highest tertile) were
      significantly more likely to die from any cause compared with subjects with the
      lowest DD values (lowest tertile) (P = .03, log-rank test). They were, however,
      no more likely to reach any of the other progression end points, including the
      primary end point (P = NS, log-rank test for all other comparisons). Multivariate
      analysis showed that DD level was a significant independent variable associated
      with occurrence of myocardial infarction (hazard ratio, 2.3; P = .02).
      CONCLUSIONS: In subjects with symptomatic PAD, elevated baseline DD, a marker of
      thrombotic activity, was significantly associated with the occurrence of
      myocardial infarction. This study did not confirm a relationship between
      progression of PAD and baseline DD or CRP during the first 3 years. Baseline DD
      and CRP do not provide useful risk stratification in patients at high risk for
      progression of symptomatic PAD. Future studies should evaluate serial levels of
      these markers to assess their utility in predicting progression of symptomatic
      PAD.

PMID- 16616238
TI  - Soft tissue sarcomas may present with deep vein thrombosis.
AB  - PURPOSE: To bring attention to our observation that soft tissue sarcomas may
      present initially as deep venous thromboses (DVTs). METHOD: A query of our health
      system database (1996 to 2004) for patients diagnosed with soft tissue sarcomas
      and DVTs was undertaken. Patient medical records were reviewed to select those
      patients whose DVT occurred before the diagnosis of their tumor. Patient
      demographics, tumor classification, presentation, and outcome were noted.
      RESULTS: Six of 19 patients were identified (four men, two women; aged 41 to 85
      years). All tumors occurred in the lower extremities. All DVTs occurred in the
      same extremity as the tumor. Pathology specimens indicated four different types
      of sarcomas. In five cases, sarcoma diagnosis was delayed as treatment of the DVT
      occurred. In one, a mass was seen on the initial venous duplex screen. Four are
      deceased, one remains in treatment, and one was lost to follow-up. The average
      length of follow-up was 10 months. CONCLUSION: Soft tissue sarcomas can initially
      present as, or even be misdiagnosed as, DVT. Given a delay in diagnosis adversely
      affects prognosis, it is important that physicians be vigilante for associated
      tumors when evaluating for suspected DVT.

PMID- 16616239
TI  - Neovalve construction in postthrombotic syndrome.
AB  - OBJECTIVE: The purpose of this study was to evaluate a new neovalve construction
      technique in postthrombotic syndrome. The surgical procedure is described, and
      preliminary results of the first case series are given. METHODS: From December
      2000 to June 2004, neovalve construction in 18 limbs was performed on 16 patients
      (8 male and 8 female; median age, 55.5 years; range, 34-79 years) to treat severe
      chronic venous insufficiency in cases of postthrombotic syndrome. Surgical
      treatment was recommended in cases of nonhealing or recurrent ulcers (CEAP
      classification class C6). Preoperative duplex scanning, ascending/descending
      venography, and air plethysmography were routinely performed. Valvular cusps were
      created by dissecting the thickened venous wall to obtain material with which to
      fashion a new monocuspid or bicuspid valve. Mean follow-up was 22 months (range,
      1-42 months). Postoperative duplex scanning and air plethysmography were
      performed in all patients. Descending venography was performed after surgery in
      15 limbs. RESULTS: In 16 lower extremities (89%), the ulcer healed within 4 to 25
      weeks (median, 12 weeks), and no recurrences occurred. Neovalve competence was
      confirmed in 17 cases (95%). Postoperative duplex scan and air plethysmography
      showed a significant improvement in hemodynamic parameters (P < .001), especially
      in younger patients with good muscle pump function. In 17 limbs (95%), the
      treated segments remained primarily patent at median follow-up of 22 months.
      Early thrombosis below the neovalve site occurred in two patients (12%). No
      perioperative pulmonary embolism was observed. A late occlusion occurred in one
      patient (6%), 8 months after surgery. Minor postoperative complications occurred
      in three patients (17%). CONCLUSIONS: Neovalve construction seems to be effective
      in restoring femoral competence in postthrombotic reflux. Although these
      preliminary results are encouraging, long-term follow-up and a larger series are
      required to validate the technique.

PMID- 16616240
TI  - Experimental pulmonary embolism: effects of the thrombus and attenuation of
      pulmonary artery injury by low-molecular-weight heparin.
AB  - BACKGROUND: Pulmonary embolism (PE) is a life-threatening condition that is
      associated with the long-term sequelae of chronic pulmonary hypertension. Prior
      experimental work has suggested that post-PE inflammation is accompanied by
      pulmonary artery intimal hyperplasia. This study evaluated the effect of the
      thrombus and tested the hypothesis that thrombolytic, antiplatelet, and
      anticoagulant agents would decrease pulmonary injury. METHODS: Male Sprague
      Dawley rats (n = 267) underwent laparotomy and temporary clip occlusion of the
      infrarenal inferior vena cava for the formation of endogenous thrombus or
      placement of an inert silicone "thrombus." Two days later, repeat laparotomy was
      performed, the clip removed, and the thrombus or silicone plug was embolized to
      the lungs. The endogenous thrombus group received normal saline, low-molecular
      weight heparin (LMWH), tissue plasminogen activator (tPA), or a gIIB/IIIA
      antagonist (abciximab). Lung tissue was harvested at various times over 21 days
      and assayed for total collagen, monocyte chemoattractant protein-1 (MCP-1),
      interleukin-13 (IL-13), and transforming growth factor-beta (TGF-beta). Fixed
      sections were stained with trichrome for intimal hyperplasia determination and ED
      1 monocytes and alpha-actin-positive staining. RESULTS: The overall survival for
      rats undergoing PE was 90%, was not affected by treatment, and 84% of all PE
      localized to the right pulmonary artery. The PE significantly reduced Pa(O2) in
      all groups. Compared with controls, the silicone emboli group had an increased
      level of IL-13 on day 1, an increased level of MCP-1 on day 4, and an increase in
      the levels of all inflammatory mediators on day 14 (P < .05). Accompanying these
      differences were greater pulmonary artery intimal hyperplasia at days 4 and 21 in
      the silicone group compared with controls (P < .05). LMWH treatment in the
      thrombus of PE rats significantly decreased IL-13 levels at all time points,
      whereas treatment with abciximab or tPA significantly increased IL-13 levels
      compared with controls. TGF-beta levels were significantly increased by LMWH at
      day 4 and 14, and abciximab was associated with lower TGF-beta at day 14. Only
      LMWH was associated with less pulmonary artery intimal hyperplasia at day 14
      compared with controls and the other treatment groups. CONCLUSIONS: Persistent
      pulmonary artery distention by an inert material is sufficient to invoke
      significant inflammation and intimal hyperplasia independent of the thrombus
      itself. Compared with nontreated PE, LMWH is the only therapy associated with a
      significant reduction in late intimal hyperplasia and, with the exception of TGF
      beta, lower profibrotic growth-factor production.

PMID- 16616241
TI  - Short-term dexamethasone treatment inhibits vein graft thickening in
      hypercholesterolemic ApoE3Leiden transgenic mice.
AB  - OBJECTIVE: The aim of this study was to assess whether the anti-inflammatory
      agent dexamethasone can inhibit vein graft thickening without the occurrence of
      serious side effects. METHODS: Venous interposition grafting was performed in the
      common carotid artery of hypercholesterolemic ApoE3Leiden transgenic mice. Mice
      were treated with dexamethasone (0.15 mg.kg(-1).d(-1) orally), and after 28 days,
      vein graft thickening was quantified. RESULTS: Treatment with dexamethasone
      resulted in a significant 43% reduction in lesion area without changes in lesion
      composition when compared with nontreated controls. However, dexamethasone, when
      administered for a prolonged period of time, is known for its potentially serious
      side effects. To overcome these potential side effects of prolonged dexamethasone
      treatment, the effect of a short-term 7-day dexamethasone treatment was studied.
      This short dexamethasone treatment resulted in a 49% decrease of vein graft
      thickening at 28 days. Furthermore, it was demonstrated that dexamethasone
      treatment led to reduced local expression of several proinflammatory cytokines
      and factors in the vein grafts 24 hours after surgery. Finally, observations in
      mice were verified in human saphenous organ cultures. Exposure to dexamethasone
      for either 7 or 28 days significantly reduced intimal hyperplasia formation on
      cultured saphenous vein segments. CONCLUSIONS: Short-term anti-inflammatory
      treatment with dexamethasone leads to a significant reduction in vein graft
      thickening over an extended period, possibly by the reduction of early expression
      of proinflammatory cytokines. This 7-day treatment minimizes the risk of unwanted
      side effects of long-term dexamethasone treatment and may be a new approach to
      prevent graft failure.

PMID- 16616242
TI  - Reconstitution of CD39 in liposomes amplifies nucleoside triphosphate
      diphosphohydrolase activity and restores thromboregulatory properties.
AB  - BACKGROUND: CD39 (nucleoside triphosphate diphosphohydrolase [NTPDase-1])
      expressed on the luminal surface of endothelial cells rapidly metabolizes
      extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to
      adenosine monophosphate (AMP), and abrogates platelet reactivity. Optimization of
      CD39 enzymatic activity appears dependent upon the expression of both
      transmembrane domains within plasma membranes. Thus, motivation exists to examine
      therapeutic antiplatelet formulations that consist of liposomal CD39. METHODS:
      Full-length human CD39 was produced by using a yeast expression system, purified,
      and reconstituted within lipid vesicles. The catalytic efficiency (kcat/Km) of
      CD39-mediated phosphohydrolysis of ADP and ATP was determined both for detergent
      solubilized and protein-reconstituted CD39 within lipid membranes. The capacity
      of CD39-containing lipid vesicles to inhibit platelet activation induced by ADP,
      collagen, or thrombin was determined in vitro by platelet aggregometry. A murine
      model of thromboplastin-induced thromboembolism was used to determine the
      effectiveness of intravenous liposomal CD39 in limiting platelet consumption and
      mortality. RESULTS: Reconstitution of human CD39 in lipid vesicles was associated
      with a decrease in Km of nearly an order of magnitude over the detergent
      solubilized form. There was a concomitant increase in both ADPase and ATPase
      catalytic efficiencies (kcat/Km ADPase: sol CD39: 2.7 x 10(6) vs liposomal CD39:
      1.4 x 10(7) min/ M; kcat/Km ATPase: sol CD39: 7.2 x 10(6) vs liposomal CD39: 2.0
      x10(7) min/M). Furthermore, CD39 lipid vesicles effectively inhibited platelet
      aggregation when activated by ADP, collagen, or thrombin, and also promoted
      platelet disaggregation (60.4% +/- 6.1%). Treatment with CD39 lipid vesicles
      preserved platelet counts after thromboplastin injection (pretreatment, 906.8 +/-
      42.9 platelets/microm3; empty vesicles, 278.6 +/- 34.8 platelets/microm3; CD39
      vesicles, 563.6 +/- 42.2 platelets/microm3; n = 10 mice/test group; P < .0001).
      In parallel survival studies, liposomal CD39 reduced mortality from 73% to 33% (P
      < or = .05; n = 12 mice/experimental test group, n = 15 mice/control test group).
      CONCLUSIONS: Incorporation of solubilized CD39 into a lipid bilayer restores
      enzyme activity and optimizes thromboregulatory potential. Treatment with CD39 in
      liposomal formulations decreased mortality in a murine model of thromboplastin
      induced thromboembolism by limiting intravascular platelet aggregation and
      thrombosis.

PMID- 16616243
TI  - Activation of the peroxynitrite-poly(adenosine diphosphate-ribose) polymerase
      pathway during neointima proliferation: a new target to prevent restenosis after
      endarterectomy.
AB  - OBJECTIVE: In a rat model of endarterectomy, we investigated the potential role
      of the peroxynitrite-poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP)
      pathway in neointima formation and the effect of pharmacologic inhibition of PARP
      on vascular remodeling. METHODS: Carotid endarterectomy was performed in male
      Sprague-Dawley rats by incision of the left carotid artery with removal of
      intima. Three groups were studied: sham-operated rats (n = 10), control rats with
      endarterectomy (n = 10) or rats with endarterectomy treated with the PARP
      inhibitor, INO-1001 (5 mg/kg daily) postoperatively (n =10). After 21 days,
      neointima formation and vascular remodeling were assessed. RESULTS:
      Immunohistochemistry analysis demonstrated activation of the peroxynitrite-PARP
      pathway with significant staining for nitrotyrosine, poly(ADP-ribose), and
      nuclear translocation of apoptosis-inducing factor (AIF) in the neointima of the
      control group. Treatment with INO-1001 significantly reduced the neointima area
      (0.024 mm2 +/- 0.019 mm2 vs 0.089 mm2 +/- 0.033 mm2 in the control group), the
      neointima/media thickness ratio (0.81 +/- 0.05 vs 2.76 +/- 1.57 in the control
      group), and the inflammation score (0.1 +/- 0.07 vs 0.3 +/- 0.12 in the control
      group) after endarterectomy. CONCLUSIONS: Pharmacologic inhibition of PARP with
      INO-1001 may be a new concept to prevent neointimal hyperplasia after
      endarterectomy.

PMID- 16616244
TI  - Successful endovascular repair of a ruptured abdominal aortic aneurysm in a
      patient with unfavorable anatomy.
AB  - Endovascular repair of an abdominal aortic aneurysm (AAA) offers hope of improved
      outcomes in patients presenting with acute rupture. However, a high proportion of
      such patients have unfavorable proximal neck anatomy and are not suitable for
      treatment with conventional endografts. Fenestrated endografts overcome the
      problem of a short proximal neck, but at present their deployment is time
      consuming and therefore not easily applicable to a ruptured AAA. In this case
      report, the authors describe a hybrid device (a composite thoracic and infrarenal
      stent graft) that was able to overcome the problem of a short wide proximal neck
      in a patient with a ruptured AAA.

PMID- 16616245
TI  - Percutaneous balloon occlusion of the inferior vena cava as an adjunct for
      treating ruptured type IV thoracoabdominal aneurysm and aortocaval fistula.
AB  - Spontaneous aortocaval fistulas are rare and thoracoabdominal aneurysms eroding
      into the inferior vena cava are rarer still. We describe a patient who presented
      to our hospital with a fistula between a Type IV thoracoabdominal aneurysm and
      the inferior vena cava. Expanding endovascular capabilities of vascular surgeons
      enabled us to insert proximal and distal occluding balloon catheters into the
      vena cava which greatly minimized blood loss.

PMID- 16616246
TI  - Delayed presentation of traumatic aortocaval fistula: a report of two cases and a
      review of the associated compensatory hemodynamic and structural changes.
AB  - Chronic aortocaval fistula (ACF) is a rare complication of gunshot wounds to the
      abdomen. Herein we report two cases of traumatic ACF: one asymptomatic and the
      other presenting with congestive heart failure (CHF) 20 and 30 years,
      respectively, after their initial injury. The recent onset of CHF, the presence
      of a continuous abdominal bruit, and, in the second patient, a history of
      penetrating trauma suggested the diagnosis of ACF. The diagnosis was confirmed by
      computed tomography scanning in both patients. Surgical repair of the ACF in the
      symptomatic patient resulted in resolution of the CHF and reversed the dilatation
      of the aorta and inferior vena cava. The asymptomatic patient was lost to follow
      up. CHF in a young male patient with a history of penetrating abdominal trauma
      should alert the surgeon to this rare complication.

PMID- 16616247
TI  - Repair of a blunt traumatic inferior vena cava laceration with commercially
      available endografts.
AB  - Endografts have recently been used in the trauma setting for arterial injuries in
      surgically inaccessible areas or in medically unstable patients. There have been
      considerably fewer reports on the use of endografts for treatment of traumatic
      venous injuries. We present the case of an endograft repair of a blunt, traumatic
      inferior vena cava injury in a patient deemed at high risk for surgical repair.

PMID- 16616248
TI  - Late spontaneous recanalization of acute internal carotid artery occlusion.
AB  - Spontaneous internal carotid recanalization has been infrequently observed, and
      when it has been reported, it has most commonly occurred early after a stroke. We
      report a case of a patient with late spontaneous recanalization of the internal
      carotid artery (ICA) that occurred within 6 months to 1 year after the initial
      diagnosis of occlusion during the course of a stroke. This event allowed the
      patient to undergo a successful surgical intervention. A suggestion is made about
      the mechanism of this phenomenon and an implication about changes in the follow
      up strategies of these patients is presented.

PMID- 16616249
TI  - Splenic malformation in a patient with Klippel-Trenaunay syndrome: a case report.
AB  - A 22-year-old woman with a diagnosis of Klippel-Trenaunay syndrome presented with
      pain in the left hypochondrium and vomiting. Investigations revealed a huge
      splenomegaly with multiple hypodense lesions and irregular, linearly enhanced
      areas. She underwent splenectomy and had good postoperative recovery.
      Histopathology showed hemangioma/lymphangioma of the spleen.

PMID- 16616250
TI  - Aortoduodenal syndrome.

PMID- 16616251
TI  - Technique of slow deployment of Gore Excluder endograft improves accuracy of
      placement.
AB  - The standard deployment of Gore Excluder endoprostheses involves rapid pulling of
      the deployment knob once the graft is thought to be properly positioned. We
      describe an alternative technique that involves the slow pulling of the
      deployment knob. The key features of this technique include anticipating the
      asymmetric flowering of the graft that occurs toward the contralateral limb,
      prompt correction of any graft malpositioning, and maintaining the slow
      deployment until the contralateral gate is released. Our experience with this
      technique demonstrates that it is accurate, safe, and reduces the need for
      proximal extension cuffs.

PMID- 16616252
TI  - Technique for safe removal of an aortic endograft with suprarenal fixation.
AB  - Complete removal of an aortic endograft with suprarenal fixation is difficult. We
      report the use of a simple device to extract a Zenith endograft. This device is
      made by cutting off the tip of the cylinder of a 20-mL syringe and rounding off
      the edges. The main body of the graft is resheathed by advancing the cylinder
      cranially while keeping the graft in a stable position. This way, the graft
      collapses and the hooks are withdrawn without tearing the wall of the aorta. The
      supraceliac clamping time in our patient was less than 2 minutes. This technique
      offers a safe and fast solution to the potentially hazardous removal of an aortic
      endograft with suprarenal fixation.

PMID- 16616253
TI  - Clinical competence statement on thoracic endovascular aortic repair (TEVAR)-
      multispecialty consensus recommendations. A report of the SVS/SIR/SCAI/SVMB
      Writing Committee to develop a clinical competence standard for TEVAR.

PMID- 16616254
TI  - Other people's money: ethics, finances, and bad outcomes.

PMID- 16616256
TI  - Regarding: "Patching versus primary closure for carotid endarterectomy".

PMID- 16616259
TI  - Regarding: "Endovascular management of spontaneous carotid artery dissection".

PMID- 16616261
TI  - Regarding "Long-term results of carotid stenting are competitive with surgery".

PMID- 16616262
TI  - Cytotoxic constituents of Achillea clavennae from Montenegro.
AB  - Examination of the aerial parts of Achillea clavennae afforded eight guaianolides
      (1-8), three bisabolenes (9-11), four flavonols (12-15), sesamin (lignan) and
      isofraxidin (coumarin). The structures of the new compounds (2, 4, 5, 7 and 10)
      were determined by spectroscopic methods. The antiproliferative action of 2, 8, 9
      and 12 were tested to HeLa, K562 and Fem-X human cancer cell lines. Guaianolides
      2 (9alpha-acetoxyartecanin) and 8 (apressin) showed significant cytotoxic effects
      to all tested lines and inducumenone (9) exhibited a moderate activity. The most
      active was flavonol centaureidin (12), already known as cytotoxic compound.

PMID- 16616263
TI  - Metabolite profiling of carotenoid and phenolic pathways in mutant and transgenic
      lines of tomato: identification of a high antioxidant fruit line.
AB  - Plant secondary metabolism is highly regulated within the major pathways to
      terpenoids, phenolics and alkaloids. Such regulation can occur at multiple levels
      from transcription through to the compartmentation of the product. However, the
      possibility exists for cross-talk between these pathways, the regulation of which
      is largely unknown at present. Such phenomena are important to understand in the
      application of plant breeding, where unintended effects of transgenesis or
      mutation can have an impact on the environment or human health. In an effort to
      improve dietary antioxidant content of crop plants, the tomato has been a major
      focus of effort for engineering both lipophilic antioxidants such as carotenoids
      and hydrophilic antioxidants such as flavonoid glycosides. In this study, a panel
      of transgenic and mutant tomato lines has been subjected to metabolite profiling
      in comparison with wild type Ailsa Craig for both carotenoids and phenolics. A
      range of mutants and transgenic lines were selected showing a range of phenotypes
      varying from down-regulation through to increased levels of lycopene and beta
      carotene. All mutants altered in structural genes for carotenoid biosynthesis
      showed that perturbations in carotenoid biosynthesis do not generally alter
      phenolic or flavonoids content significantly even when devoid of carotenoids.
      Reciprocally, the down-regulation of ferulate 5-hydroxylase had no effect on
      carotenoid content. In contrast mutants defective in light perception such as the
      high pigment (hp-1) and LA3771 possess elevated chlorogenic acid and rutin as
      well as increased carotenoid content. These lines can act as the hosts for
      further genetic manipulation for increased antioxidant content.

PMID- 16616264
TI  - Alanine racemase of alfalfa seedlings (Medicago sativa L.): first evidence for
      the presence of an amino acid racemase in plants.
AB  - We demonstrated several kinds of D-amino acids in plant seedlings, and moreover
      alanine racemase (E.C.5.1.1.1) in alfalfa (Medicago sativa L.) seedlings. This is
      the first evidence for the presence of amino acid racemase in plant. The enzyme
      was effectively induced by the addition of L- or D-alanine, and we highly
      purified the enzyme to show enzymological properties. The enzyme exclusively
      catalyzed racemization of L- and D-alanine. The K(m) and V(max) values of enzyme
      for L-alanine were 29.6 x 10(-3) M and 1.02 mol/s/kg, and those for D-alanine are
      12.0 x 10(-3) M and 0.44 mol/s/kg, respectively. The K(eq) value was estimated to
      be about 1 and indicated that the enzyme catalyzes a typical racemization of both
      enantiomers of alanine. The enzyme was inactivated by hydroxylamine,
      phenylhydrazine and some other pyridoxal 5'-phosphate enzyme inhibitors.
      Accordingly, the enzyme required pyridoxal 5'-phosphate as a coenzyme, and
      enzymologically resembled bacterial alanine racemases studied so far.

PMID- 16616266
TI  - Pain rehabilitation.

PMID- 16616267
TI  - Pain in patient groups frequently treated by physiatrists.
AB  - This article highlights the significant prevalence and impact of pain in persons
      who have disabilities and points to the need for additional research in this
      area. Theory-driven research examining biopsychosocial models of and treatments
      for chronic pain are the important next steps in this area. The extensive
      literature on persons in whom pain is the primary disability provides a useful
      basis for such research. Pain may be one of several problems facing
      rehabilitation professionals in their care of persons with disabilities.
      Nonetheless, given the suffering associated with it, pain warrants careful
      assessment and, as indicated, intervention.

PMID- 16616268
TI  - Central hypersensitivity in chronic pain: mechanisms and clinical implications.
AB  - The available literature consistently shows increased pain sensitivity after
      sensory stimulation of healthy tissues in patients who have various chronic pain
      conditions. This indicates a state of hypersensitivity of the CNS that amplifies
      the nociceptive input arising from damaged tissues. Experimental data indicate
      that central hypersensitivity is probably induced primarily by nociceptive input
      arising from a diseased tissue. In patients, imbalance of descending modulatory
      systems connected with psychologic distress may play a role. There is
      experimental support in animal studies for the persistence of central
      hypersensitivity after complete resolution of tissue damage. This is particularly
      true for neuropathic pain conditions, whereby potentially irreversible plasticity
      changes of the CNS have been documented in animal studies. Whether such changes
      are present in musculoskeletal pain states is at present uncertain. Despite the
      likely importance of central hypersensitivity in the pathophysiology of chronic
      pain, this mechanism should not be used to justify the lack of understanding on
      the anatomic origin of the pain complaints in several pain syndromes, which is
      mostly due to limitations of the available diagnostic tools. Treatment strategies
      for central hypersensitivity in patients have been investigated mostly in
      neuropathic pain states. Possible therapy modalities for central hypersensitivity
      in chronic pain of musculoskeletal origin are largely unexplored. The limited
      evidence available and everyday practice show, at best, modest efficacy of the
      available treatment modalities for central hypersensitivity. The gap between
      basic knowledge and clinical benefits remains large and should stimulate further
      intensive research.

PMID- 16616269
TI  - Patient evaluation and general treatment planning.
AB  - Treating pain patients is difficult. The usual problems encountered in providing
      coherent and effective treatment for any chronic medical illness are compounded
      in painful conditions by time, society's choices, and the cultural role of the
      patient. Effective treatment of these patients depends on the persistence of the
      clinician. We must persist in requiring a complete history to understand the
      patient and his or her problem. We must persist in performing a thorough physical
      examination to uncover sufficient under-standing of the patient's physiology. We
      must persist in developing a comprehensive treatment plan to cover all of the
      intervening concerns. We must persist in following the patient in the clinic to
      make sure that the plan is completed and that complications that arise are dealt
      with efficiently. This can lead to considerable satisfaction and frustration.
      There remain many unanswered questions in the evaluation of pain patients and of
      pain itself. How accurate is physical examination in providing information about
      a given patient that is relevant to treating pain? Can physical examination
      reliably elicit a nociceptive focus for a specific individual's chronic pain
      experience? Is all long-term pain a smorgasbord of nociceptive, central
      sensitization, and neuromodulatory mechanisms? Can acute pain be more
      consistently aborted to minimize the development of chronic pain? Over the next
      few years, as our expanding knowledge of neuropharmacology, neurophysiology, and
      pain modulation in the CNS combines with better understanding of pain psychology
      and sociology, we clinicians will expect to have happier and more productive
      patients.

PMID- 16616270
TI  - Physical agents used in the management of chronic pain by physical therapists.
AB  - Evidence supporting the use of specific physical agents in the management of
      chronic pain conditions is not definitive; it is largely incomplete and sometimes
      contradictory. However, the use of agents in chronic pain management programs is
      common. Within the broad use of physical agents, they are rarely the sole
      modality of treatment. A 1995 American Physical Therapy Association position
      statement asserts that "Without documentation which justifies the necessity of
      the exclusive use of physical agents/modalities, the use of physical
      agents/modalities, in the absence of other skilled therapeutic or educational
      intervention, should not be considered physical therapy". Physical agents may
      serve as useful adjunctive modalities of pain relief or to enhance the
      effectiveness of other elements in therapy geared toward resolution of movement
      impairments and restoration of physical function. Given that a conclusive
      aggregate of findings is unlikely to exist for all permutations of patient
      conditions, combined with interacting therapeutic modalities, an evidence-based
      approach to pain management is not always possible or beneficial to the patient.
      In the face of inconclusive evidence, a theory-based approach may help determine
      if the therapeutic effect ofa given physical agent has the possibility of being a
      useful clinical tool in the context of treating a particular patient's mechanism
      of pain generation. Until controlled efficacy findings are definitive, careful
      individual patient response monitoring of thoughtful theoretical application of
      adjunctive physical agents may be a prudent approach to the management of chronic
      pain.

PMID- 16616271
TI  - Nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs, including COX-2 selective drugs, are often
      used for acute and chronic musculoskeletal pain,including osteoarthritis, trauma,
      overuse syndromes, and compression fractures. Although these medications are
      often well tolerated in the young and otherwise healthy patient, the chronic use
      of these medications can lead to multiple medical problems, most commonly related
      to the gastrointestinal tract. Recently, concerns about cardiovascular adverse
      effects have been raised, particularly in the COX-2 drugs. Dosing and duration of
      therapy should be adjusted for comorbidities. CBC and renal and hepatic function
      should be checked at intervals of 3 to 6 months, depending on the patient.

PMID- 16616272
TI  - Opioids in the treatment of chronic pain: legal framework and therapeutic
      indications and limitations.
AB  - The most important message that physicians must communicate to persons with
      chronic pain is that, currently, no medication exists that will take away more
      than 30% of the pain they experience. Chronic pain is a chronic disease and, like
      diabetes or hypertension, requires chronic concessions and lifestyle
      modifications. In controlled trials of short duration and small sample size with
      highly selected patients, patients sustaining moderate-to-severe pain still
      experience moderate pain even on opioid medication. Adverse drug effects are
      predictable and common, and, in fact, long-term compliance with opioids is low
      owing to side effects. Screening for substance abuse by history taking, observing
      behavior, obtaining old medical records,and using UDS in patients before
      initiating opioid therapy is important to identify patients with comorbid
      addictive disease who require coincident or antecedent treatment. Familiarity
      with federal and state controlled substance legislation and state health care
      provider and pain treatment acts is a mundane but essential educational endeavor
      for all physicians prescribing opioids. If physicians educate their patients with
      chronic pain about the limited efficacy of the medications, patients'
      expectations for drug treatment can be more realistic.

PMID- 16616273
TI  - Antidepressant and anticonvulsant medication for chronic pain.
AB  - Antidepressants and anticonvulsants have been shown to be efficacious in the
      treatment of neuropathic pain, chronic headache, and other chronic pain
      conditions. They may be useful in the treatment of disorders in which central
      nervous system hypersensitivity con-tributes to pain. They provide valuable
      alternatives or adjuncts to the use of opioid medications in the treatment of
      chronic pain. Antidepressants have several potential roles in the treatment of
      chronic pain in addition to their analgesic effects. Specifically, they
      effectively address the sleep disturbance, depression, and anxiety that are
      common in patients with chronic pain.

PMID- 16616274
TI  - Muscle relaxants and antispasticity agents.
AB  - Muscle relaxants make up a heterogeneous group of agents and can have a
      clinically significant role in the treatment of chronic muscle pain. These
      medications are not without possible serious side effects; hence, care should be
      taken in deciding on their appropriateness and ongoing monitoring performed, if
      prescribed.

PMID- 16616275
TI  - Psychologic interventions for chronic pain.
AB  - As a biopsychosocial understanding of chronic pain has become more sophisticated
      during recent decades, a variety of psychologically based treatment approaches
      have been developed and empirically validated for helping people better manage
      their pain. These approaches to pain management have much to offer persons with
      chronic pain in terms of enhancing quality of life and pain-related coping, as
      well as reducing disability and pain-related interference with functioning.
      Although some treatments, like hypnotic analgesia, may require referral to a
      specialized provider, several of the principles of other psychologically based
      treatment approaches for pain management (eg, operant behavioral therapy,
      cognitive-behavioral therapy, motivational interviewing) can easily be integrated
      into work with persons with pain in a rehabilitation setting. Rehabilitation
      providers who are interested in incorporating these treatment strategies into
      their clinical work who do not have prior exposure to these approaches are
      encouraged to review the suggested references and to seek out related training
      opportunities.

PMID- 16616276
TI  - Multidisciplinary and interdisciplinary management of chronic pain.
AB  - Multidisciplinary and interdisciplinary pain management programs incorporate a
      biopsychosocial model in assessing and treating pain and result in pain
      reduction, improved quality of life, and psychosocial functioning. Additionally,
      return-to-work and vocational outcomes may be seen in selected patients.
      Treatment teams may include a physiatrist, a physical or occupational therapist,a
      pain psychologist, a relaxation (biofeedback) therapist, vocational and
      therapeutic recreational therapists, social workers, and nurses. The key
      component to program success is collaborative ongoing communication among team
      members, the patient, and the case manager.

PMID- 16616277
TI  - Complementary medicine in chronic pain treatment.
AB  - This chapter looks at therapies that are considered "alternative" to conventional
      medical approaches. A definition of "complementary and alternative" medicine is
      considered in the context of the complex and clinically challenging field of pain
      medicine. A rationale for studying unorthodox treatments of chronic pain is
      presented. The challenges of an evidence-based approach to incorporating
      complementary therapies are explored, and a brief survey of several commonly
      available complementary medicine therapies is provided.

PMID- 16616278
TI  - Traumatic brain injury and pain.
AB  - The co-occurrence of traumatic brain injury (TBI) and pain is quite frequent and
      presents a number of challenges to the medical practitioner. The distinct nature
      and extent of these challenges calls for considering the co-existence of TBI and
      pain a unique medical entity. Clearly, from a research standpoint, the area is in
      its infancy. The clinician is often left with adapting standard techniques
      effective for evaluating and treating pain in patients without TBI. Such
      adaptations require a readiness to recognize how pain affects the presence and
      course of TBI-related symptoms and, in turn, how TBI symptoms affect the presence
      and course of pain. Given the myriad factors that can affect outcome, effective
      evaluation and treatment of this co-occurring problem need to rely on a
      biopsychosocial model, which encourages consideration of a broad perspective of
      possible causes and care approaches as well as use of multiple disciplines.

PMID- 16616279
TI  - Treatment of fibromyalgia, myofascial pain, and related disorders.
AB  - Chronic muscle pain is a common complaint among patients who seek care for
      musculoskeletal disorders. A spectrum of clinical presentations exists, ranging
      from focal or regional complaints that usually represent myofascial pain
      syndromes to more wide spread pain that may meet criteria for a diagnosis of
      fibromyalgia. This article addresses the epidemiology, pathophysiology, and
      clinical management of myofascial pain syndrome and fibromyalgia. These
      conditions are challenging to treat and require physiatrists to be aware of the
      wide range of pharmacologic, rehabilitative,and psychosocial interventions that
      can be helpful.

PMID- 16616280
TI  - Targeted therapies: a nursing perspective.
AB  - OBJECTIVES: To review the development of targeted therapies and the biology of
      relevant therapeutic targets. To analyze the relevance of targeted agents as part
      of current clinical practice. DATA SOURCES: Research articles. CONCLUSION:
      Several targeted agents are now available for clinical use. Their mechanisms of
      action are more specific against tumor cells than traditional cytotoxics.
      Monotherapy regimens based on targeted agents tend to be better tolerated than
      chemotherapy, and most combination regimens with targeted agents have proven
      feasible. Their availability has greatly expanded cancer treatment options,
      especially for chemorefractory patients. IMPLICATIONS FOR NURSING PRACTICE:
      Nurses involved in the care of patients with cancer can benefit from an increased
      understanding of targeted therapies, including their mechanisms of action, their
      efficacy profile, as well as prophylaxis and management of adverse events and
      administration procedures.

PMID- 16616281
TI  - EGFR as a target: rationale for therapy.
AB  - OBJECTIVES: To review the biology of the EGFR, its structure, and the associated
      signal transduction pathways. To provide an overview of the role of EGFR in
      normal physiology and the pathophysiology of malignancy. Current anti-EGFR
      treatments are also discussed. DATA SOURCES: Research articles. CONCLUSION: EGFR
      is a valid target in the treatment of solid tumors. EGFR abnormalities and
      dysfunction are involved in various aspects of carcinogenesis and tumor
      progression, and EGFR is overexpressed in several tumor types. The development of
      anti-EGFR therapies represents an important advance in cancer therapy.
      IMPLICATIONS FOR NURSING PRACTICE: Anti-EGFR therapy is currently available in
      the clinical setting. Nurses involved in the care of patients with cancer can
      benefit from an increased understanding of the normal and abnormal function of
      EGFR in the body and the mechanisms by which anti-EGFR therapies act.

PMID- 16616282
TI  - Clinical experience with anti-EGFR therapy.
AB  - OBJECTIVES: To review clinical experience and studies with anti-EGFR therapies in
      metastatic CRC, SCCHN, and NSCLC. Case studies in each tumor type will also be
      outlined. DATA SOURCES: Research articles and patient case histories. CONCLUSION:
      Several phase II/III trials have shown the activity of anti-EGFR therapy in CRC,
      SCCHN, and NSCLC. Treatment confers substantial clinical benefit with improved
      symptoms, particularly in previously treated patients. Toxicity of anti-EGFR
      therapies is generally manageable and non-overlapping with other treatment
      options, including chemotherapy and radiotherapy. IMPLICATIONS FOR NURSING
      PRACTICE: It is important for nurses to further advance our understanding of anti
      EGFR therapies and continue to encourage patient enrollment in ongoing trials of
      anti-EGFR therapy.

PMID- 16616283
TI  - Administration of anti-EGFR therapy: a practical review.
AB  - OBJECTIVES: To highlight key issues in the administration of cancer therapies
      that target the EGFR. DATA SOURCES: Published clinical trials of anti-EGFR
      therapy, secondary literature on the administration of anticancer drugs, and
      illustrative case study reports. CONCLUSION: Anti-EGFR agents represent a new
      class of therapy. It is important for nurses to acquire familiarity with the
      specific issues related to the administration of anti-EGFR agents. Preparedness
      and active patient monitoring can minimize the impact of toxicities (including
      interstitial lung disease, infusion reactions, and metabolic alterations) and
      help ensure the delivery of full treatment courses. IMPLICATIONS FOR NURSING
      PRACTICE: Nurses familiar with the administration issues and the severe adverse
      events associated with anti-EGFR therapy will be better equipped to manage them
      effectively.

PMID- 16616284
TI  - Common side effects of anti-EGFR therapy: acneform rash.
AB  - OBJECTIVES: To review the general toxicity profile of EGFR-targeted therapies and
      the management of the most common side effect, skin toxicity. DATA SOURCES:
      Research articles. CONCLUSION: The most common side effect of anti-EGFR therapy
      is skin toxicity, which is generally mild to moderate, but may be severe in up to
      18% of patients. Appearance of more severe rash has been correlated with better
      treatment outcomes. Skin toxicity is generally manageable with standard topical
      or systemic antibiotics and anti-inflammatory agents. Rash does not warrant
      treatment discontinuation; however, when using TKIs, the combination of rash and
      severe diarrhea may require treatment cessation. IMPLICATIONS FOR NURSING
      PRACTICE: Patients and nurses need to be well informed about the expected side
      effects of anti-EGFR therapy and appropriate management techniques. Patient
      education prior to beginning therapy and proactive intervention at the first
      signs of skin toxicity are key to successful management.

PMID- 16616285
TI  - Sexual dimorphism in esterified steroid levels in the gastropod Marisa
      cornuarietis: the effect of xenoandrogenic compounds.
AB  - Molluscs can conjugate a variety of steroids to form fatty acid esters. In this
      work, the freshwater ramshorn snail Marisa cornuarietis was used to investigate
      sex differences in endogenous levels of esterified steroids. Testosterone and
      estradiol were mainly found in the esterified form in the digestive gland/gonad
      complex of M. cornuarietis, and males had higher levels of esterified steroids
      than females (4-10-fold). Additionally, the ability of several xenobiotics,
      namely tributyltin (TBT), methyltestosterone (MT) and fenarimol (FEN) to
      interfere with the esterification of testosterone and estradiol was investigated.
      All three compounds induced imposex - appearance of male sexual characteristics
      in females. Exposure to TBT led to a decrease in both esterified testosterone (60
      85%) and estradiol (16-53%) in females after 100 days exposure, but had no effect
      on males. Exposure to FEN and MT did not alter levels of esterified steroids in
      males or in females, although exposed females developed imposex after 150 days
      exposure. The decrease in esterified steroids by TBT could not be directly linked
      with a decrease in microsomal acyl-CoA:testosterone acyltransferase (ATAT)
      activity, which catalyzes the esterification of steroids. In fact, ATAT activity
      was marginally induced in organisms exposed to TBT for 50 days (1.3-fold), and
      significantly induced in males and females exposed to MT for 50 days (1.8- and
      1.5-fold, respectively), whereas no effect on ATAT activity was observed after
      150 days exposure.

PMID- 16616286
TI  - Exaggerated adrenarche and altered cortisol metabolism in Type 1 diabetic
      children.
AB  - Reported literature data strongly suggest that steroid metabolism is dysregulated
      in Type 1 diabetes mellitus. The aim of this study was to non-invasively examine
      the cortisol metabolism in children with Type 1 diabetes mellitus (T1DM) in
      detail and to test the hypothesis that adrenarche is affected under conventional
      intensive insulin therapy. In 24-h urine samples of 109 patients aged 4-18 years
      with T1DM of more than 1 year, steroids were profiled using gas chromatography
      mass spectrometry. Additionally, urinary free cortisol (UFF) and cortisone (UFE)
      were quantified by RIA after extraction and chromatographic purification. Data on
      urinary steroids from 400 healthy controls served as reference values. Enzyme
      activities were assessed by established steroid metabolite ratios, e.g. 5alpha
      reductase and 11beta-hydroxysteroid dehydrogenase Type 2 (11beta-HSD2) by 5alpha
      tetrahydrocortisol/tetrahydrocortisol and UFE/UFF, respectively. Urinary markers
      of adrenarche, especially dehydroepiandrosterone and its direct metabolites were
      elevated in patients, as were urinary 6beta-hydroxycortisol, UFE, and 11beta-HSD2
      activity. However, overall cortisol secretion, as reflected by the sum of major
      urinary cortisol metabolites, was mostly normal and activity of 5alpha-reductase
      clearly reduced. Our study provides evidence for an exaggerated adrenarche in
      T1DM children, which may help to understand reported sequelae in female patients
      like hyperandrogenic symptoms. The findings also suggest a reduced cortisol
      inactivation via 5alpha-reductase that is not compensated by a fall in cortisol
      secretion. Whether the elevated urinary 6beta-hydroxycortisol and cortisone
      excretion, observed in the patients, are also present in other forms of
      hypercortisolism and may thus serve as non-invasive clinical stress markers
      deserves further study.

PMID- 16616287
TI  - Polyvalent HIV-1 Env vaccine formulations delivered by the DNA priming plus
      protein boosting approach are effective in generating neutralizing antibodies
      against primary human immunodeficiency virus type 1 isolates from subtypes A, B,
      C, D and E.
AB  - A major challenge in developing an HIV-1 vaccine is to identify immunogens and
      their delivery methods that can elicit broad neutralizing antibodies against
      primary isolates of different genetic subtypes. Recently, we demonstrated that
      priming with DNA vaccines expressing primary HIV-1 envelope glycoprotein (Env)
      followed by recombinant Env protein boosting was successful in generating
      positive neutralizing antibody responses against a clade B primary HIV-1 isolate,
      JR-FL, that was not easily neutralized. In the current study, we examined whether
      the DNA priming plus recombinant protein boosting approach delivering a
      polyvalent primary Env formulation was able to generate neutralizing antibodies
      against primary HIV-1 viral isolates from various genetic subtypes. New Zealand
      White rabbits were first immunized with DNA vaccines expressing one, three or
      eight primary HIV-1 gp120 antigens delivered by a gene gun followed by
      recombinant gp120 protein boosting. Neutralizing antibody responses were examined
      by two independently executed neutralization assays: the first one was a single
      round infection neutralization assay against a panel of 10 primary HIV-1 isolates
      of subtypes A, B, C and E and the second one used the PhenoSense assay against a
      panel of 12 pseudovirues expressing primary HIV-1 Env antigens from subtypes A,
      B, C, D and E as well as 2 pseudoviruses expressing the Env antigens from MN and
      NL4-3 viruses. Rabbit sera immunized with the DNA priming plus protein boosting
      approach, but not DNA vaccine alone or Env protein alone, were capable of
      neutralizing 7 of 10 viruses in the first assay and 12 of 14 viruses in the
      second assay. More importantly, sera immunized with the polyvalent Env antigens
      were able to neutralize a significantly higher percentage of viruses than the
      sera immunized with the monovalent antigens. Our results suggest that DNA priming
      followed by recombinant Env protein boosting can be used to deliver polyvalent
      Env-antigen-based HIV-1 vaccines to elicit neutralizing antibody responses
      against viruses with diverse genetic sequence variations.

PMID- 16616288
TI  - Dominant-negative effect of hetero-oligomerization on the function of the human
      immunodeficiency virus type 1 envelope glycoprotein complex.
AB  - The human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein forms
      trimers that mediate interactions with the CD4 receptor and a co-receptor on the
      target cell surface, thereby triggering viral fusion with the cell membrane.
      Cleavage of Env into its surface, gp120, and transmembrane, gp41, moieties is
      necessary for activation of its fusogenicity. Here, we produced pseudoviruses
      with phenotypically mixed wild-type (Wt) and mutant, cleavage-incompetent Env in
      order to quantify the effects of incorporating uncleaved Env on virion
      infectivity, antigenicity and neutralization sensitivity. We modeled the relative
      infectivity of three such phenotypically mixed viral strains, JR-FL, HXBc2 and a
      derivative of the latter, 3.2P, as a function of the relative amount of Wt Env.
      The data were fit very closely (R(2) > 0.99) by models which assumed that only Wt
      homotrimers were functional, with different approximate thresholds of critical
      numbers of functional trimers per virion for the three strains. We also produced
      3.2P pseudoviruses containing both a cleavage-competent Env that is defective for
      binding the neutralizing monoclonal antibody (NAb) 2G12, and a cleavage
      incompetent Env that binds 2G12. The 2G12 NAb was not able to reduce the
      infectivity of these pseudoviruses detectably. Their neutralization by the CD4
      binding site-directed agents CD4-IgG2 and NAb b12 was also unaffected by 2G12
      binding to uncleaved Env. These results further strengthen the conclusion that
      only homotrimers consisting of cleaved Env are functional. They also imply that
      the function of a trimer is unaffected sterically by the binding of an antibody
      to an adjacent trimer.

PMID- 16616289
TI  - Promoter switching allows simultaneous transcription of LANA and K14/vGPCR of
      Kaposi's sarcoma-associated herpesvirus.
AB  - Latent transcription of the latency-associated nuclear antigen (LANA/ORF73) of
      Kaposi's sarcoma-associated herpesvirus is driven by the LANAp-c. Complexity
      arises during lytic reactivation, however, as the bicistronic K14/vGPCR
      transcript initiates 32 bp downstream of LANAp-c in the opposite orientation. We
      identify an Rta/ORF50-inducible LANA promoter (LANAp-i) that is distinct from the
      LANAp-c. LANAp-c is unaffected by Rta/ORF50. Utilization of the second,
      downstream LANAp-i explains how LANA and K14/vGPCR are simultaneously transcribed
      during de novo infection or lytic reactivation. Transactivation of LANAp-i and
      K14/vGPCRp requires the C-terminal activation domain of Rta/ORF50 and is mediated
      by DNA-binding-dependent and -independent Rta/ORF50 mechanisms. Transcriptional
      profiling following viral reactivation support promoter reporter phenotypes. In
      sum, cis-elements within the LANAp were selected to ensure faithful expression of
      LANA and other genes regulated by LANAp during all stages of the KSHV lifecycle
      despite potential interference from K14/vGPCRp activity.

PMID- 16616290
TI  - Peroxisome proliferator-activated receptor-gamma agonists inhibit the replication
      of respiratory syncytial virus (RSV) in human lung epithelial cells.
AB  - We have previously shown that peroxisome proliferator-activated receptor-gamma
      (PPARgamma) agonists inhibited the inflammatory response of RSV-infected human
      lung epithelial cells. In this study, we supply evidence that specific PPARgamma
      agonists (15d-PGJ2, ciglitazone, troglitazone, Fmoc-Leu) efficiently blocked the
      RSV-induced cytotoxicity and development of syncytia in tissue culture (A549, HEp
      2). All PPARgamma agonists under study markedly inhibited the cell surface
      expression of the viral G and F protein on RSV-infected A549 cells. This was
      paralleled by a reduced cellular amount of N protein-encoding mRNA determined by
      real-time RT-PCR. Concomitantly, a reduced release of infectious progeny virus
      into the cell supernatants of human lung epithelial cells (A549, normal human
      bronchial epithelial cells (NHBE)) was observed. Similar results were obtained
      regardless whether PPARgamma agonists were added prior to RSV infection or
      thereafter, suggesting that the agonists inhibited viral gene expression and not
      the primary adhesion or fusion process.

PMID- 16616291
TI  - Chemometrics in monitoring spatial and temporal variations in drinking water
      quality.
AB  - This case study reports multivariate techniques applied for the evaluation of
      temporal/spatial variations and interpretation of monitoring data obtained by the
      determination of chloro/bromo disinfection by-products in drinking water at 12
      locations in the Gdansk area (Poland), over the period 1993-2000. The complex
      data matrix (1756 observations) was treated with various multivariate techniques.
      Cluster analysis (CA) was successful, yielding two different groups of similarity
      reflecting different types of drinking water supplied (surface and groundwater).
      The locations supplied in general with groundwater could be further classified
      into two subgroups, depending on whether the groundwater was mixed with surface
      water or not. Analysis of variance (ANOVA) was used to classify and thus confirm
      the groups found by means of cluster analysis and proved the existence of
      statistically significant differences between the concentration levels of CHCl3,
      CHBrCl2+C2HCl3, CHBr2Cl, and CH2Cl2 in the samples collected. Of all the
      variables evaluated, only three were characterized by statistically significant
      correlations (CHCl3, CHBrCl2+C2HCl3, CHBr2Cl). The analysis of correlation
      coefficients revealed that chloroform formed as the main chlorinated disinfection
      by-product and, furthermore, the natural presence of bromide in water (both
      ground and surface) results in the formation of brominated disinfection by
      products (DBPs). Temporal variations of volatile organic chlorinated compounds
      (VOCls) were also evaluated by multidimensional ANOVA. Observation of temporal
      changes in the concentration of VOCls at the location supplied with both surface
      and groundwater reveals a steady improvement in drinking water quality. In
      general, the study shows the importance of drinking water monitoring in
      connection with simple but powerful statistical tools to better understand
      spatial and temporal variations in water quality.

PMID- 16616292
TI  - Study of the cellular retention time and the partial biomass renovation in a
      fungal decolourisation continuous process.
AB  - The long-term continuous decolourisation treatment of the textile dye Grey
      Lanaset G (150 mg/l) was carried out in an air-pulsed bed bioreactor with
      retained pellets of the white-rot fungus Trametes versicolor. Maximum cellular
      retention time (CRT) was established at 40 days. During this time period, colour
      reduction remained at 90% and laccase activity was over 400 AU/l. Higher CRTs
      involved operational problems related to biomass conglomerates formed at the top
      of the bioreactor, which made individual movement of the pellets difficult. In
      order to carry out the long-term continuous treatment, a strategy of purge and
      biomass renovation that had to allow fungal stable activity levels to be
      maintained was planned. The purge and biomass renovation strategy consists of
      partial biomass renovations: 1/3 of the total biomass of the system is renewed
      every 1/3 of the CRT. Different CRTs were tested; with a CRT of 21 days carrying
      out partial biomass renovations every 7 days and with a hydraulic retention time
      of 2 days, decolourisation percentages higher than 80% were obtained, maintaining
      a young culture in the bioreactor and guaranteeing microbial activity. In
      accordance with the strategy observed, different simulations of the age of the
      biomass in the bioreactor were carried out, obtaining suitable age distributions
      for CRT of 20-21 days.

PMID- 16616293
TI  - Lipid peroxidation and antioxidant status in blood and tissue of malignant breast
      tumor and benign breast disease.
AB  - Changes in the levels of malondialdehyde (MDA), nitrate and nitrite (as an index
      of nitric oxide production), lipid hydroperoxide (LOH), total antioxidant
      capacity (TAC), lipids (total cholesterol and triglycerides) and lipoproteins
      (HDL- and LDL-cholesterol) were estimated in breast cancer patients (n = 15) and
      benign breast disease (n = 15). Serum and tissue MDA levels were found to be
      decreased in breast cancer patients compared to the benign group (p < 0.05). In
      contrast, nitrate and nitrite levels were increased in serum and tissue of the
      cancer group compared to benign breast disease patients (p < 0.05). Compared to
      the benign group, tissue TAC levels were elevated in the breast cancer patient
      group (p < 0.05). Total cholesterol and HDL-cholesterol were elevated in the
      benign group compared with cancer patients (p < 0.05). These findings support the
      hypothesis that lipid peroxidation in serum and tissue of benign breast disease
      is greater than in breast cancer. However, the enhanced levels of nitric oxide
      may be in response to inflammation in patients with breast cancer. Total
      antioxidant status is lower in benign tissue than in cancerous tissue, probably
      to compensate for this elevated free radical production.

PMID- 16616295
TI  - Organic contaminant loads into the Western Mediterranean Sea: estimate of Ebro
      River inputs.
AB  - Annual input estimates for several organic contaminants from the Ebro River into
      the Northwestern Mediterranean Sea were carried out on the basis of monthly
      sampling from November 2002 to October 2003. Some organochlorine compounds (DDT
      and its degradation products, DDD and DDE, PCBs (9 congeners), HCB and gamma-HCH)
      were selected due to their reported occurrence in the river. Furthermore, some
      polar pesticides used in the Ebro Delta were also determined (atrazine, simazine,
      diazinon, fenitrothion and molinate). Concentrations ranged from 0.4 to 19.5 ng
      l(-1) for the organochlorine compounds (sum of particulate and dissolved phases)
      and from not detected (ND) to 170 ng l(-1) for the more polar pesticides, which
      were only found in the dissolved phase. The sum of PCB congeners (mean 8.9 ng l(
      1)) showed the highest concentrations among the organochlorine compounds and
      atrazine (mean 82 ng l(-1)) among the polar pesticides. Based on the contaminant
      concentrations and on hydrological data, contaminant discharges into the sea were
      estimated amounting in total to 167 and 1,258 kg year(-1) of organochlorine
      compounds and polar pesticides, respectively. Furthermore, it was observed that
      PCBs, DDTs and HCB inputs were basically influenced by spate periods due to an
      increase in suspended particulate matter associated to runoff and sediment
      resuspension. Whereas for more water soluble contaminants, such as the
      agrochemicals, their seasonal use had a higher incidence in contaminant fluxes.
      Bulk chemical parameters such as SPM, DOC, POC, %OC, %ON and C/N ratio provided
      additional information on the organic matter sources. This provides a better
      understanding of the temporal variability of the contaminant concentrations.

PMID- 16616296
TI  - Simplified spectrophotometric method using methylene blue for determining anionic
      surfactants: applications to the study of primary biodegradation in aerobic
      screening tests.
AB  - In the present work, we propose a simplified spectrophotometric method for
      determining anionic surfactants, based on the formation of the ionic pair anionic
      surfactant-methylene blue (AS-MB). This method, in relation to the conventional
      analytic procedure, considerably reduces not only the quantity of chloroform used
      in extracting the ionic pair formed, but also the time and the quantity of sample
      necessary to perform the assay, eliminating the filtration stage. The method has
      been simplified by displacing the transfer equilibrium of the ionic pair AS-MB
      towards the organic phase, augmenting the volumetric relationship of
      chloroform/sample. The method proposed has been applied in the study of primary
      biodegradation kinetics of linear alkylbenzenesulfonate (LAS).

PMID- 16616298
TI  - Biology of the hair follicle: the basics.
AB  - The mammalian hair follicle represents a unique, highly regenerative
      neuroectodermal-mesodermal interaction system that contains numerous stem cells.
      It is the only organ in the mammalian organism that undergoes life-long cycles of
      rapid growth (anagen), regression (catagen), and resting periods (telogen). These
      transformations are controlled by changes in the local signaling milieu, based on
      changes in expression/activity of a constantly growing number of cytokines,
      hormones, neurotransmitters, and their cognate receptors as well as of
      transcription factors and enzymes that have become recognized as key mediators of
      hair follicle cycling. Transplantation experiments have shown that the driving
      force of cycling, the "hair cycle clock," is located in the hair follicle itself.
      However, the exact underlying molecular mechanisms that drive this oscillator
      system remain unclear. These controls of hair follicle cycling are of great
      clinical interest because hair loss or unwanted hair growth largely reflect
      undesired changes in hair follicle cycling. To develop therapeutic agents for the
      management of these hair cycle abnormalities, it is critical to decipher and
      pharmacologically target the key molecular controls that underlie the enigmatic
      "hair cycle clock."

PMID- 16616299
TI  - Clinical approach to the patient with alopecia.
AB  - Hair loss, or alopecia, is a common patient complaint and a source of significant
      psychological and physical distress. The majority of common hair loss disorders
      can be accurately diagnosed in the outpatient setting with a systematic
      evaluation of the patient. This review will present a clinical approach to the
      patient with alopecia by describing the history, clinical findings, and diagnosis
      of various hair loss disorders.

PMID- 16616300
TI  - Office diagnosis of hair shaft defects.
AB  - Hair shaft abnormalities are fascinating and can provide a diagnostic challenge.
      Current knowledge of structural changes in hair has been amplified by scanning
      and transmission electron microscopy (SEM and TEM). Dermatologists using the
      light microscope and polarization in the office can diagnose the great majority
      of hair shaft defects. A number of these defects are illustrated here.

PMID- 16616301
TI  - The histopathology of noncicatricial alopecia.
AB  - During the past 2 decades, the use of transverse sections in the evaluation of
      scalp biopsy specimens has led to a better understanding of the histopathologic
      changes in both cicatricial and noncicatricial alopecia. However, the technique
      has provided the most significant gains in the study of the latter type of
      alopecia, where evaluation of follicle density and follicular dynamics are
      integral to accurate diagnosis. This report reviews the histopathologic findings
      of four common types of noncicatricial alopecia: androgenetic alopecia, telogen
      effluvium, alopecia areata, and trichotillomania/chronic traction alopecia.

PMID- 16616302
TI  - The histopathology of primary cicatricial alopecia.
AB  - Alopecia typically is divided into cicatricial (scarring) and noncicatricial
      (nonscarring) forms. "Scarring" alopecia implies that follicular epithelium has
      been replaced by connective tissue and is therefore an irreversible process. In
      contrast, nonscarring alopecia is potentially reversible as follicular epithelia
      remain intact. Classification of cicatricial alopecia can be confusing and
      controversial as most disorders demonstrate overlapping clinical and histologic
      features. Herein, we present an overview of the histologic assessment of
      cicatricial alopecia, including an algorithmic approach to the evaluation of
      biopsy specimens from patients with scarring alopecia.

PMID- 16616303
TI  - Medical treatment of noncicatricial alopecia.
AB  - Androgenetic alopecia, alopecia areata, and telogen effluvium are the primary
      nonscarring alopecias found in clinical practice. Androgenetic alopecia is
      considered to be the most common form of human alopecia and is postulated to
      affect more than 50% of men by age 50. Alopecia areata affects up to 2% of the
      U.S. population. Telogen effluvium frequently occurs after major life events,
      such as a severe illness, childbirth, or high fever, and may be associated with
      the use of certain medications or iron deficiency, particularly in women. The
      focus of this review is on the medical treatment of these common hair loss
      conditions.

PMID- 16616304
TI  - The medical treatment of cicatricial alopecia.
AB  - The best outcome of current treatments of cicatricial alopecia is induction of a
      clinical remission with arrest of symptoms and signs, but the progression of hair
      loss may continue insidiously. Current treatments do not arrest the underlying
      disease process. A scalp biopsy is the first step in management. Selection of
      treatment described herein is guided by the histopathologic findings, including
      the type, location and extent of the predominant cellular inflammatory
      infiltrate, and clinical disease activity. Cicatricial alopecias with
      predominantly lymphocytic infiltrates are treated with immunomodulating agents,
      and those with predominantly neutrophilic infiltrates are treated with
      antimicrobial agents. Treatment selection may be challenging and requires
      flexibility, as histopathologic features frequently overlap, are not clear cut,
      or change over time. In the future, cellular and molecular biology studies will
      hopefully identify unique markers for the clinically distinct cicatricial
      alopecias and lead to better treatments and a cure.

PMID- 16616305
TI  - Hair transplantation for men and women.
AB  - The goal of hair transplantation is to restore a natural, undetectable frame of
      hair to the face. From the 1960s into the late 1990s, using 10 to 25 hair, 3-4 mm
      grafts was the mainstay of hair transplantation, despite the fact hair naturally
      grows in the scalp in bundles of 1 to 4 hair follicles. The 10 to 25 hair grafts
      looked unnatural because they were unnatural on the scalp. Today, surgeons
      meticulously harvest the natural 1 to 4 hair follicular groupings from donor hair
      and implant them in the recipient region in men and women. This technique
      consistently creates natural-appearing hair. Women can benefit from
      transplantation as much as men.

PMID- 16616306
TI  - Differential decline in behavioral performance of Drosophila melanogaster with
      age.
AB  - Normal aging is typically accompanied by deficits in behavioral performance,
      independent of overt pathology. In contrast, some behaviors remain relatively
      unchanged with age, but the reason(s) they remain intact are not known. Here we
      compare the relative impact of age on a battery of standard behavioral tests
      using the model genetic organism Drosophila melanogaster. Consistent with
      previous reports, learning, locomotion, geotaxis and phototaxis show a dramatic
      and progressive decline beginning at 1-2 weeks of age. In contrast, using two
      independent behavioral assays, we observe little or no decline in the flies'
      ability to escape potentially threatening stimuli. Using the assay with the most
      rapid decline, geotaxis, we observe a delay in functional aging in a long-lived
      mutant of the Ecdysone Receptor. We discuss the use of Drosophila genetics to
      investigate the differential decline in behavioral capacity.

PMID- 16616308
TI  - Branchial cleft and arch anomalies in children.
AB  - Branchial anomalies are important lesions to consider in the differential
      diagnosis of head and neck masses in children. These anomalies are composed of a
      heterogeneous group of congenital malformations that arise from incomplete
      obliteration of pharyngeal clefts and pouches during embryogenesis. Although
      present at birth, many abnormalities do not become evident until later in infancy
      or childhood. It is common for branchial anomalies to become infected, causing
      significant morbidity. Surgical removal may be difficult, and inadequate
      resection of the lesion is likely to cause recurrence. Understanding the
      embryology and anatomy of these lesions is essential to the provision of adequate
      therapy.

PMID- 16616309
TI  - Thyroglossal duct and other congenital midline cervical anomalies.
AB  - Thyroglossal duct anomalies and dermoid cysts comprise the vast majority of
      congenital midline cervical masses seen in children. Unusual lesions of the
      midline neck include ranulae and midline cervical clefts. Workup and management
      is lesion-dependent, and an accurate preoperative diagnosis is essential for
      planning and performing an appropriate surgical procedure. This discussion
      presents an overview of the relevant embryology, pathophysiology, and diagnostic
      modalities for these congenital midline cervical anomalies. Additionally, the
      current principles of surgical management are described.

PMID- 16616310
TI  - Pediatric salivary gland lesions.
AB  - The salivary glands comprise three main pairs of glands (ie, the parotid, the
      submandibular, and the sublingual) and a number of minor glands found in the
      mucosa of the upper aerodigestive tract. Lesions may be inflammatory or
      obstructive in nature or may stem from granulomatous or neoplastic disease. As
      such, establishing a definitive diagnosis is often quite challenging. This
      article reviews widely used diagnostic approaches and briefly describes various
      salivary gland lesions within an etiologic framework.

PMID- 16616311
TI  - Thyroid and parathyroid disease in children.
AB  - Although diseases of the thyroid and parathyroid glands are relatively uncommon
      in children, the implications of missed diagnoses can be severe. This review
      describes the embryology, anatomy, and physiology of the thyroid and parathyroid
      glands, and focuses on significant benign and malignant pathologies of these
      glands.

PMID- 16616312
TI  - Malignant neoplasms of the head and neck.
AB  - Head and neck masses represent a common clinical entity in children. In general,
      these masses are classified as developmental, inflammatory, or neoplastic. Having
      a working knowledge of lesions within this region and conducting a thorough
      history and physical examination generally enables the clinician to facilitate an
      appropriate workup and establish a diagnosis. The differential diagnosis is
      broad, and expeditiously distinguishing benign from malignant masses is critical
      for instituting a timely multidisciplinary approach to the management of
      malignant lesions. Neoplasms of the head and neck account for approximately 5% of
      all childhood malignancies. A diagnosis of malignancy may represent a primary
      tumor or metastatic foci to cervical nodes. In this review, we discuss the
      general approach to evaluating suspicious masses and adenopathy in the head and
      neck region and summarize the most common malignant neoplasms of the head and
      neck with regard to their incidence, clinical presentation, diagnostic
      evaluation, staging, and management. Thyroid, parathyroid, and salivary gland
      tumors are discussed elsewhere in this issue of Seminars in Pediatric Surgery.

PMID- 16616313
TI  - Acute, subacute, and chronic cervical lymphadenitis in children.
AB  - Lymphadenopathy refers to any disease process involving lymph nodes that are
      abnormal in size and consistency. Lymphadenitis specifically refers to
      lymphadenopathies that are caused by inflammatory processes. Cervical
      lymphadenopathy is a common problem in the pediatric age group and is largely
      inflammatory and infectious in etiology. Although most patients are treated
      successfully by their primary care physician, surgical consultation is frequently
      required for patients who fail to respond to initial therapy or for those in whom
      there is an index of suspicion for a neoplastic process. This article addresses
      current approaches to the diagnosis and management of cervical lymphadenitis in
      children.

PMID- 16616314
TI  - The EXIT procedure: principles, pitfalls, and progress.
AB  - Although performing procedures on a fetus before severing the umbilical cord has
      previously been reported, the principles of the ex utero intrapartum treatment
      (EXIT) procedure were first fully developed for reversing tracheal occlusion in
      fetuses with severe congenital diaphragmatic hernia. The EXIT procedure offers
      the advantage of insuring uteroplacental gas exchange while on placental support.
      The lessons learned in the development of the principles that underlie the EXIT
      procedure have improved outcomes when applied in other conditions, most notably
      in cases of airway obstruction. The range of indications for the EXIT procedure
      has expanded and currently includes giant fetal neck masses, lung or mediastinal
      tumors, congenital high airway obstruction syndrome, and EXIT to ECMO
      (extracorporeal membrane oxygenation), among others. This review summarizes the
      underlying principles of the EXIT procedure, the expanding indications for its
      use, the pitfalls of management, and the progress that has been made in its
      successful application.

PMID- 16616315
TI  - Evaluation and management of upper airway disorders in children.
AB  - Upper airway disorders in children may be divided into those that are congenital
      in origin and those that are acquired. The presentation and management of these
      disorders is significantly influenced both by the anatomic location of the
      pathology, which is usually obstructive in nature, and by the severity of the
      obstruction. This discussion provides an overview of the presentation, diagnosis,
      management, and potential complications of the most commonly seen upper airway
      disorders. These disorders are presented within an anatomic framework,
      progressing from proximal at the nares to distal at the carina.

PMID- 16616316
TI  - Cervicofacial vascular anomalies. I. Hemangiomas and other benign vascular
      tumors.
AB  - Before the early 1980s, the lack of an accepted system of nomenclature for
      vascular anomalies created confusion and frustration for clinicians and patients
      alike. Scientific advances over the past two decades have, however, led to
      international consensus among experts on a system of disease classification that
      comprises vascular tumors and vascular malformations. The most common vascular
      tumor is hemangioma, which is frequently seen in the head and neck area. Some
      hemangiomas are best left untreated, whereas others may cause significant
      complications and disfigurement, thus requiring intervention. Early recognition
      and treatment of complications is imperative. This is best accomplished in an
      interdisciplinary setting, where collaborative treatment strategies are planned
      on an individual basis. Steroids are the first line of medical treatment.
      Chemotherapy with vincristine is an effective treatment for complicated lesions,
      although it requires further evaluation through prospective clinical trials.
      Because of known neurotoxicity, interferon is used as a last resort, especially
      in children younger than 1 year of age. Laser therapy and surgical excision are
      also important therapeutic modalities. This article presents an overview of
      hemangiomas and other vascular tumors, highlighting cervicofacial lesions and
      describing critical and underappreciated clinical presentations.

PMID- 16616317
TI  - Cervicofacial vascular anomalies. II. Vascular malformations.
AB  - Vascular malformations are the second major category of vascular anomalies. In
      contrast to vascular tumors, they are present at birth and grow commensurately
      with the child. Although the molecular mechanisms underlying the formation of
      these lesions remain unclear, lesions are known to result from abnormal
      development and morphogenesis. Histologic examination of vascular malformations
      shows no evidence of cellular proliferation, but rather progressive dilation of
      abnormal channels. Vascular malformations are designated according to their
      predominant channel type; they may be capillary, venous, lymphatic, arterial, and
      combined malformations. Malformations with an arterial component are
      rheologically fast-flow, whereas capillary, lymphatic, and venous malformations
      are slow-flow in nature. The morbidity of vascular malformations varies greatly
      both within and among the clinical subgroups cited above. This article describes
      the clinical presentation, diagnosis, and management of vascular malformations.
      The more frequently encountered clinical presentations involving the head and
      neck are highlighted.

PMID- 16616318
TI  - Modelling the effect of climate change on recovery of acidified freshwaters:
      relative sensitivity of individual processes in the MAGIC model.
AB  - The MAGIC model was used to evaluate the relative sensitivity of several possible
      climate-induced effects on the recovery of soil and surface water from
      acidification. A common protocol was used at 14 intensively studied sites in
      Europe and eastern North America. The results show that several of the factors
      are of only minor importance (increase in pCO(2) in soil air and runoff, for
      example), several are important at only a few sites (seasalts at near-coastal
      sites, for example) and several are important at nearly all sites (increased
      concentrations of organic acids in soil solution and runoff, for example). In
      addition changes in forest growth and decomposition of soil organic matter are
      important at forested sites and sites at risk of nitrogen saturation. The trials
      suggest that in future modelling of recovery from acidification should take into
      account possible concurrent climate changes and focus specially on the climate
      induced changes in organic acids and nitrogen retention.

PMID- 16616319
TI  - Climate variability and forecasting surface water recovery from acidification:
      modelling drought-induced sulphate release from wetlands.
AB  - Climate-induced drought events have been shown to have a significant influence on
      sulphate (SO(4)(2-)) export from forested catchments in central Ontario,
      subsequently delaying recovery of surface waters from acidification. Field and
      modelling studies have demonstrated that water table drawdown during drought
      periods promotes oxidation of previously stored (reduced) sulphur (S) compounds
      in wetlands, with subsequent efflux of SO(4)(2-) upon re-wetting. Although
      climate-induced changes in processes are generally not integrated into soil
      acidification models, MAGIC (Model of Acidification of Groundwater in Catchments)
      includes a wetland compartment that incorporates redox processes driven by
      drought events. The potential confounding influence of climate-induced drought
      events on acidification recovery at Plastic Lake, south-central Ontario (under
      proposed future S emission reductions) was investigated using MAGIC and two
      climate scenarios: monthly precipitation and runoff based on long-term means
      (average-climate scenario), and variable precipitation and runoff based on the
      past 20 years of observed monthly data (variable-climate scenario). The variable
      climate scenario included several periods of summer drought owing to lower than
      average rainfall and higher then average temperature. Nonetheless, long-term
      regional trends in precipitation and temperature suggest that the variable
      climate scenario may be a conservative estimate of future climate. The average
      climate scenario indicated good recovery potential with acid neutralising
      capacity (ANC) reaching approximately 40 micromol(c)L(-1) by 2020 and 50
      micromol(c)L(-1) by 2080. In contrast, the forecasted recovery potential under
      the variable-climate scenario was very much reduced. By 2080, ANC was forecasted
      to increase to 2.6 micromol(c)L(-1) from -10.0 micromol(c)L(-1) in 2000. Elevated
      SO(4)(2-) efflux following drought events (introduced under the variable-climate
      scenario) has a dramatic impact on simulated future surface water chemistry. The
      results clearly demonstrate that prediction of future water quality, using models
      such as MAGIC, should take into account changes or variability in climate as well
      as acid deposition.

PMID- 16616320
TI  - Does delta15N in river food webs reflect the intensity and origin of N loads from
      the watershed?
AB  - Stable nitrogen isotope ratios (delta15N) were measured in invertebrates and fish
      collected from 82 river sites located in the Saint-Lawrence Lowlands in Quebec,
      Canada, to examine the relationship between aquatic biota delta15N and
      anthropogenic nitrogen (N) loads. Mean delta15N values of all three trophic
      levels examined (primary consumers, predatory invertebrates and invertebrate
      feeding fish) were highly correlated with total anthropogenic N loads on the
      watershed (kg N km-2 year-1; r2>0.61, p<0.0001) and with N loads originating from
      livestock manure (r2>0.62, p<0.0001), synthetic fertilizers (r2>0.45, p<0.0001),
      and human population (r2>0.29, p<0.0001), respectively. Significant relationships
      were also observed between primary consumer delta15N and N loads originating from
      each of the three livestock species examined (bovines, pigs and poultry;
      p<0.0001). Furthermore, all three animal species contributed significantly and
      independently in elevating primary consumer delta15N (multiple r2=0.67,
      p<0.0001). Curvilinear regressions were observed at all levels of analysis,
      delta15N values increasing slowly over a wide range of low levels of N loads, but
      increasing much faster as N loads grew larger. The three anthropogenic N sources
      examined were highly correlated with one another, preventing us from
      statistically isolating their respective effects on delta15N. When these loads
      were expressed as a proportion of total N load, delta15N of aquatic biota was
      still highly correlated with N from livestock and fertilizers, but not with N
      from human population. Overall, these results suggest that delta15N values of
      aquatic consumers could be used as indicators of the intensity of anthropogenic N
      loading on watersheds, but not as tracers of the relative importance of
      individual N sources.

PMID- 16616321
TI  - Anaerobic biotransformation of estrogens.
AB  - Estrogens are important environmental contaminants that disrupt endocrine systems
      and feminize male fish. We investigated the potential for anaerobic
      biodegradation of the estrogens 17-alpha-ethynylestradiol (EE2) and 17-beta
      estradiol (E2) in order to understand their fate in aquatic and terrestrial
      environments. Cultures were established using lake water and sediment under
      methanogenic, sulfate-, iron-, and nitrate-reducing conditions. Anaerobic
      degradation of EE2 (added at 5 mg/L) was not observed in multiple trials over
      long incubation periods (over three years). E2 (added at 5 mg/L) was transformed
      to estrone (E1) under all four anaerobic conditions (99-176 microg L-1 day-1),
      but the extent of conversion was different for each electron acceptor. The
      oxidation of E2 to E1 was not inhibited by E1. Under some conditions, reversible
      inter-conversion of E2 and E1 was observed, and the final steady state
      concentration of E2 depended on the electron-accepting condition but was
      independent of the total amount of estrogens added. In addition, racemization
      occurred and E1 was also transformed to 17-alpha-estradiol under all but nitrate
      reducing conditions. Although E2 could be readily transformed to E1 and in many
      cases 17-alpha-estradiol under anaerobic conditions, the complete degradation of
      estrogens under these conditions was minimal, suggesting that they would
      accumulate in anoxic environments.

PMID- 16616322
TI  - Clinical experience of prophylactic treatment in von Willebrand disease.
AB  - The prophylactic treatment of bleeding in von Willebrand disease (vWD) has a long
      history in Sweden, having been first initiated in the late 1950s. The clinical
      experience of the prophylaxis of vWD in Sweden is described in the current review
      of a retrospective study of 37 patients from three haemophilia centres receiving
      prophylaxis for vWD. Prophylaxis with a plasma concentrate (fraction I-0 or
      Factor VIII) effectively reduced the median number of bleeds per year, prevented
      joint arthropathy in those who started prophylaxis at a young age, and improved
      the quality of life of all patients with vWD, particularly those with type 3
      disease. This study demonstrates that the long-term prophylactic treatment with
      von Willebrand Factor (vWF)/FVIII concentrate (Haemate-P, ZLB Behring) in vWD is
      warranted in the majority of patients with type 3 disease.

PMID- 16616323
TI  - Prophylaxis in rare coagulation disorders -- factor XIII deficiency.
AB  - Factor XIII (FXIII) deficiency is a very rare form of haemophilia resulting in
      different manifestations of bleeding disorders, but characterised by umbilical
      stump bleeding in up to 80% of patients. Although originally described as the
      final enzyme in the clotting cascade, FXIII is now recognised to play a role
      throughout the clotting process. Treatment with FXIII concentrate (Fibrogammin P,
      ZLB Behring) results in the re-establishment of a normal clotting pattern.
      Prophylaxis studies in France and the USA have demonstrated an excellent response
      following monthly prophylaxis with this plasma-derived, pasteurised concentrate.
      Patients with FXIII deficiency have good control of bleeding, with no development
      of inhibitors, or viral seroconversion. The development of registries such as
      that in the USA will enable the different manifestations of the disease to be
      explored.

PMID- 16616324
TI  - Mild hyperhomocysteinemia is associated with a decreased fibrinolytic activity in
      patients after ST-elevation myocardial infarction.
AB  - BACKGROUND: Elevated homocysteine (Hcy) levels have been associated with
      increased risk for cardiovascular disease and it has been shown that
      hyperhomocysteinemia is associated with increased levels of t-PA antigen in
      individuals without evidence for coronary artery disease (CAD). The aim of this
      study was to examine if Hcy plasma levels are associated with plasma levels of
      fibrinolytic factors in patients with CAD and a history of acute myocardial
      infarction. METHODS: We measured in 56 patients with CAD, 1 month after their
      first ST-elevation myocardial infarction, plasma levels of Hcy, the fibrinolytic
      parameters tissue-type plasminogen activator (t-PA), plasminogen activator
      inhibitor-type-1 (PAI-1), and t-PA-PAI-1 complexes. RESULTS: Hcy plasma levels
      inversely correlated with t-PA activity (r=-0.303, p<0.05). Patients with mild
      hyperhomocysteinemia (Hcy>15 micromol/L, n=8) showed significantly lower plasma
      levels of t-PA activity (p<0.05). Regression analysis revealed that out of
      cardiovascular risk factors and medical treatment only Hcy was significantly
      associated with t-PA activity. CONCLUSIONS: Patients with CAD after a first
      myocardial infarction and hyperhomocysteinemia show a reduced t-PA activity
      independently from cardiovascular risk factors and medical treatment.
      Homocysteine lowering therapies may increase fibrinolytic activity and thereby
      may help to avoid atherothrombotic events in patients with CAD after a first
      myocardial infarction.

PMID- 16616325
TI  - Long-term health risk to the skin of ultraviolet radiation.
AB  - The major well-proven long-term health risks of excessive exposure to ultraviolet
      (UV) radiation relate to the skin. Premalignant skin lesions are seen very much
      earlier in white skinned populations exposed to excessive sunlight, and over time
      these same individuals develop larger numbers of all of the three major skin
      cancers than individuals who do not experience excessive UV exposure. These three
      skin cancers are squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and
      malignant melanoma. In the case of SCC the major aetiological pattern is chronic
      long-term exposure, but for BCCs the pattern appears to be slightly different
      with short-term burning episodes being more important. In the case of melanomas,
      there is evidence that for the 4 main types of melanomas, the pattern of excess
      UV exposure which is most injurious varies.

PMID- 16616326
TI  - Considering the potential benefits as well as adverse effects of sun exposure:
      can all the potential benefits be provided by oral vitamin D supplementation?
AB  - Exposure to ultraviolet radiation (UVR) is associated with both adverse and
      beneficial health effects. While many of the adverse effects of excessive
      exposure are well known, the adverse effects of insufficient UVR exposure are
      less clear-cut, but may include a heightened risk of several cancers and
      autoimmune disorders as well as of bone diseases such as rickets, osteomalacia
      and osteoporosis. Although some of the postulated beneficial effects of UVR
      exposure may occur through the maintenance of adequate levels of vitamin D, it is
      not clear that this can account for all of these effects. We briefly review the
      epidemiological literature with respect to vitamin D, UVR exposure and autoimmune
      diseases. We further outline alternative pathways, whereby UVR could alter the
      risk of development of some cancers and autoimmune disorders, independent of
      effects on vitamin D synthesis. Recognition of the beneficial effects of UVR
      exposure has led to a reconsideration of sun avoidance policies. It is important
      to recognize that all of the beneficial effects of UVR exposure may not occur
      only through UVR-induced vitamin D synthesis. Thus maintaining current sun
      avoidance policies while supplementing food with vitamin D may not be sufficient
      to avoid the risks of insufficient exposure to UVR.

PMID- 16616327
TI  - Sexual rehabilitation medicine in a female oncology setting.
AB  - Comprehensive oncological care has recently expanded not only to include
      diagnosis and treatment but survivorship medicine as well. Tertiary health care
      facilities are now developing multidisciplinary survivorship programs that focus
      on helping cancer patients live active, fulfilled lives while dealing with the
      potentially damaging and longstanding sexual ramifications of cancer and cancer
      therapy. As part of a growing trend, health care institutions are establishing
      specialized sexual health programs to address cancer patients' sexual needs using
      functionalized survivorship curricula. Such programs provide individual or
      couples management to men and women who suffer from sexual dysfunction as a
      result of a cancer diagnosis and/or treatment. Using the Sexual Health Program at
      the Memorial Sloan-Kettering Cancer Center as a prototype for the development of
      future sexual health programs, this article will discuss the specific components
      and benefits of such programs. An effective program focuses on 4 key issues
      clinical care, patient education and support, medical and scientific research,
      and medical education and training for health care professionals and providers.
      This article will discuss how sexual health programs benefit the female cancer
      patient (it should be noted, however, that these programs, such as the one at our
      institution, are usually available for either sex).

PMID- 16616328
TI  - Structural basis of multimer-mediated mayhem.
AB  - Oligomerization of AML1-ETO contributes to leukemogenesis through obscure
      mechanisms. In this issue of Cancer Cell, Bushweller and colleagues show the
      crystal structure of the ETO NHR2 domain to be a tetramer. Tetramer formation is
      important for maturation arrest and self-renewal, and gene expression is altered
      in the absence of self-association. Loss of oligomer formation disrupts
      interactions between AML1-ETO and members of the ETO corepressor family, but not
      other corepressor molecules posited to be important for leukemogenesis. The
      findings clarify the role of oligomer formation in AML1-ETO function and suggest
      a possible therapeutic strategy of targeting ETO-corepressor interactions.

PMID- 16616329
TI  - Ras ubiquitination: coupling spatial sorting and signal transmission.
AB  - H-Ras, N-Ras, and K-Ras proteins have distinct biological properties, despite
      ubiquitous expression and similar affinities for regulators and effectors. C
      terminal hypervariable regions that distinguish H-Ras, N-Ras, and K-Ras proteins
      direct them to distinct membrane compartments, where they may encounter
      regulators and effectors at different local concentrations. Jura and coworkers
      now report that these membrane-targeting domains direct differential
      ubiquitination of Ras proteins and so provide a molecular mechanism to explain
      the sorting process and, perhaps, some of the dramatic differences in biological
      potency among H-Ras, N-Ras, and K-Ras proteins.

PMID- 16616330
TI  - In the pursuit of complexity: systems medicine in cancer biology.
AB  - Adler et al., in a paper appearing in Nature Genetics, exploited the intersect of
      genetic information from expression profiles with that from array comparative
      genomic hybridization in human breast cancers to identify genes that may induce
      the transcription of the prognostic "wound response" expression signature. The
      amplification of two genes, MYC and CSN5, appeared to be correlated with the
      wound response cassette. In vitro validation showed that the wound signature
      could be induced in MCF10A cells only when MYC and CSN5 were coexpressed. This
      work shows that the intersect analysis of gene amplification and transcriptional
      expression on a genome-wide scale can uncover complex conditional interactions
      embedded in the systems map of transcriptional regulation.

PMID- 16616331
TI  - The tetramer structure of the Nervy homology two domain, NHR2, is critical for
      AML1/ETO's activity.
AB  - AML1/ETO is the chimeric protein resulting from the t(8;21) in acute myeloid
      leukemia. The Nervy homology 2 (NHR2) domain in ETO mediates oligomerization and
      AML1/ETO's interactions with ETO, MTGR1, and MTG16, and with the corepressor
      molecules mSin3A and HDAC1 and HDAC3. We solved the NHR2 domain structure and
      found it to be an alpha-helical tetramer. We show that oligomerization
      contributes to AML1/ETO's inhibition of granulocyte differentiation, is essential
      for its ability to enhance the clonogenic potential of primary mouse bone marrow
      cells, and affects AML1/ETO's activity on several endogenous genes.
      Oligomerization is also required for AML1/ETO's interactions with ETO, MTGR1, and
      MTG16, but not with other corepressor molecules.

PMID- 16616332
TI  - Tumor invasion in the absence of epithelial-mesenchymal transition: podoplanin
      mediated remodeling of the actin cytoskeleton.
AB  - The expression of podoplanin, a small mucin-like protein, is upregulated in the
      invasive front of a number of human carcinomas. We have investigated podoplanin
      function in cultured human breast cancer cells, in a mouse model of pancreatic
      beta cell carcinogenesis, and in human cancer biopsies. Our results indicate that
      podoplanin promotes tumor cell invasion in vitro and in vivo. Notably, the
      expression and subcellular localization of epithelial markers are unaltered, and
      mesenchymal markers are not induced in invasive podoplanin-expressing tumor
      cells. Rather, podoplanin induces collective cell migration by filopodia
      formation via the downregulation of the activities of small Rho family GTPases.
      In conclusion, podoplanin induces an alternative pathway of tumor cell invasion
      in the absence of epithelial-mesenchymal transition (EMT).

PMID- 16616333
TI  - A mouse p53 mutant lacking the proline-rich domain rescues Mdm4 deficiency and
      provides insight into the Mdm2-Mdm4-p53 regulatory network.
AB  - The mechanisms by which Mdm2 and Mdm4 (MdmX) regulate p53 remain controversial.
      We generated a mouse encoding p53 lacking the proline-rich domain (p53DeltaP).
      p53DeltaP exhibited increased sensitivity to Mdm2-dependent degradation and
      decreased transactivation capacity, correlating with deficient cell cycle arrest
      and reduced apoptotic responses. p53DeltaP induced lethality in Mdm2-/- embryos,
      but not in Mdm4-/- embryos. Mdm4 loss did not alter Mdm2 stability but
      significantly increased p53DeltaP transactivation to partially restore cycle
      control. In contrast, decreasing Mdm2 levels increased p53DeltaP levels without
      altering p53DeltaP transactivation. Thus, Mdm4 regulates p53 activity, while Mdm2
      mainly controls p53 stability. Furthermore, Mdm4 loss dramatically improved
      p53DeltaP-mediated suppression of oncogene-induced tumors, emphasizing the
      importance of targeting Mdm4 in chemotherapies designed to activate p53.

PMID- 16616334
TI  - Neuronal and glioma-derived stem cell factor induces angiogenesis within the
      brain.
AB  - Stem cell factor (SCF) is overexpressed by neurons following brain injury as well
      as by glioma cells; however, its role in gliomagenesis remains unclear. Here, we
      demonstrate that SCF directly activates brain microvascular endothelial cells
      (ECs) in vitro and induces a potent angiogenic response in vivo. Primary human
      gliomas express SCF in a grade-dependent manner and induce normal neurons to
      express SCF in brain regions infiltrated by glioma cells, areas that colocalize
      with prominent angiogenesis. Downregulation of SCF inhibits tumor-mediated
      angiogenesis and glioma growth in vivo, whereas overexpression of SCF is
      associated with shorter survival in patients with malignant gliomas. Thus, the
      SCF/c-Kit pathway plays an important role in tumor- and normal host cell-induced
      angiogenesis within the brain.

PMID- 16616335
TI  - The stress-regulated protein p8 mediates cannabinoid-induced apoptosis of tumor
      cells.
AB  - One of the most exciting areas of current research in the cannabinoid field is
      the study of the potential application of these compounds as antitumoral drugs.
      Here, we describe the signaling pathway that mediates cannabinoid-induced
      apoptosis of tumor cells. By using a wide array of experimental approaches, we
      identify the stress-regulated protein p8 (also designated as candidate of
      metastasis 1) as an essential mediator of cannabinoid antitumoral action and show
      that p8 upregulation is dependent on de novo-synthesized ceramide. We also
      observe that p8 mediates its apoptotic effect via upregulation of the endoplasmic
      reticulum stress-related genes ATF-4, CHOP, and TRB3. Activation of this pathway
      may constitute a potential therapeutic strategy for inhibiting tumor growth.

PMID- 16616336
TI  - High-resolution genomic profiles define distinct clinico-pathogenetic subgroups
      of multiple myeloma patients.
AB  - To identify genetic events underlying the genesis and progression of multiple
      myeloma (MM), we conducted a high-resolution analysis of recurrent copy number
      alterations (CNAs) and expression profiles in a collection of MM cell lines and
      outcome-annotated clinical specimens. Attesting to the molecular heterogeneity of
      MM, unsupervised classification using nonnegative matrix factorization (NMF)
      designed for array comparative genomic hybridization (aCGH) analysis uncovered
      distinct genomic subtypes. Additionally, we defined 87 discrete minimal common
      regions (MCRs) within recurrent and highly focal CNAs. Further integration with
      expression data generated a refined list of MM gene candidates residing within
      these MCRs, thereby providing a genomic framework for dissection of disease
      pathogenesis, improved clinical management, and initiation of targeted drug
      discovery for specific MM patients.

PMID- 16616337
TI  - Effect of solid storage on caprine semen conservation at 5 degrees C.
AB  - In this work, we investigated the effect of storage in solid-phase extender on
      buck semen conserved at 5 degrees C. Furthermore, we studied the effect of
      addition of cysteine to the extender and the washing of seminal plasma on sperm
      survival. In Experiment 1, milk-based extender (M) was used as a control to study
      the effect of solid media storage (G) and cysteine supplementation (C), and the
      combination of both (GC), on in vitro sperm survival of washed and non-washed
      semen, conserved up to 72 h at 5 degrees C. Motility, acrosome integrity (NAR)
      and hypo-osmotic swelling tests (HOST) were evaluated to assess in vitro sperm
      survival. In Experiment 2, an artificial insemination (AI) field trial was
      performed to compare G versus M. Solid media (G) maintained motility of
      spermatozoa during storage higher than any other extender (67% G versus 62% GC;
      61% M and 59% C; P<0.05), but there was no difference in NAR or HOST between
      extenders (P>0.05). No improvement in sperm viability was obtained by addition of
      cysteine to the media. Washing of semen improved motility (65% versus 60%;
      P<0.05), NAR (70% versus 64%; P<0.05) and HOST (37% versus 28%; P<0.05). No
      significant differences in fertility were obtained between G and M extenders (47%
      versus 41%; P>0.05). In conclusion, washing of semen and dilution in gelatin
      supplemented milk extender (solid storage) appears to be a successful method for
      goat semen storage at 5 degrees C.

PMID- 16616338
TI  - Investigations on reproductive physiology in the male Eurasian lynx (Lynx lynx).
AB  - This study characterized (in vivo) morphological and functional parameters of
      reproductive organs of adult male lynx (n = 3) prior to, during, and after the
      breeding season (n = 3). Size and morphology of the reproductive tract were
      monitored by transcutaneous (testes) and transrectal (accessory sex glands)
      ultrasonography. Semen was collected by electroejaculation. Ejaculate volume,
      sperm number, motility, and morphology of spermatozoa as well as testosterone
      concentrations in blood serum and feces were evaluated. The testes and prostate
      had seasonal changes in size and echotexture. The mean (+/- S.D.) maximum and
      minimum testicular volume were 2.8 +/- 0.8 cm3 and 1.5 +/- 0.3 cm3, respectively.
      Fecal testosterone concentrations were highest in February (1240 +/- 393 ng/g
      feces), with a second increase in May (971 +/- 202 ng/g feces), but
      concentrations were lowest in January (481 +/- 52.9 ng/g feces). Ejaculate
      volume, total sperm number and percentage of motile, and intact spermatozoa were
      maximal in March (the middle of the breeding season). In one of the eight
      litters, multiple paternity was proven; however, in the remaining seven litters,
      all 16 cubs were sired by the same male. This particular male had the most
      developed and active testes and best semen quality, which may be important for
      sperm competition.

PMID- 16616339
TI  - Eosinophilic hepatitis caused by lamotrigine.

PMID- 16616340
TI  - A case of double gastric tumors treated by endoscopic submucosal dissection plus
      pylorus-preserving gastrectomy as a less radical treatment strategy.

PMID- 16616341
TI  - Cytomegalovirus infection in a liver transplant patient identified by
      endoscopically severe duodenal papillitis.

PMID- 16616342
TI  - Systematic review on epidemiology of gastroesophageal reflux disease in Asia.
AB  - BACKGROUND & AIMS: The epidemiology of gastroesophageal reflux disease (GERD) has
      been a subject of much interest in recent years. This review ascertains the
      prevalence of GERD in eastern and southeastern Asia, and reports on complications
      and risk factors. METHODS: This qualitative systematic review of the epidemiology
      of GERD in eastern and southeastern Asia identified studies in adults reported in
      English in the Medline database (searched through April 2005), relevant reviews,
      and our own bibliographic databases. RESULTS: Thirteen studies were included. The
      reported population prevalence of GERD in eastern Asia ranged from 2.5% to 6.7%
      for at least weekly symptoms of heartburn and/or acid regurgitation and may be
      increasing. No reliable data are available on the prevalence of esophagitis in
      the general population. In case studies, the prevalence of reflux esophagitis
      ranged from 3.4% to 16.3%. Well-established risk factors for GERD in Asian
      populations included hiatus hernia and obesity. Age and male sex also may be risk
      factors. Chest pain is the predominant extraesophageal manifestation of GERD in
      China, whereas in Japan, a link with asthma has been implicated in patients with
      severe esophagitis. CONCLUSIONS: There is a paucity of studies reporting the
      prevalence of GERD in eastern and southeastern Asia. These results highlight the
      need for further epidemiologic studies using representative study populations and
      a standardized methodology. Recognition and awareness of GERD need to increase
      concomitantly to ensure appropriate diagnosis and treatment of the disease.

PMID- 16616343
TI  - Peutz-Jeghers syndrome and management recommendations.
AB  - Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease caused by germline
      mutation of the serine threonine kinase 11 and characterized by hamartomatous
      polyps in the gastrointestinal tract and mucocutaneous melanin pigmentation.
      Patients with PJS are at increased risk for common and unusual types of
      gastrointestinal and nongastrointestinal tumors. This review analyzes currently
      available literature and describes the clinical characteristics of PJS, assesses
      the risk of malignancy in this disorder, and delineates management and
      surveillance recommendations for affected individuals.

PMID- 16616344
TI  - A review of the genomics of gastric cancer.
AB  - Gastric cancer is the fourth most common cancer and the second leading cause of
      cancer-related death in the world. Over the past 2 decades, many exciting
      discoveries regarding the genomics of gastric cancer have been made. There are 2
      distinct histologic types of gastric adenocarcinoma, and these types differ in
      their epidemiology, pathogenesis, genetic profile, and clinical outcome. The
      development of new approaches to functional genomics has significantly improved
      our ability to explore molecular alterations underlying gastric carcinogenesis
      and progression. The pathogenesis of intestinal-type gastric cancer follows a
      multistep progression that usually is initiated by H pylori infection. A wide
      range of genetic and epigenetic abnormalities including point mutation, loss of
      heterozygosity, microsatellite instability, and hypermethylation are described in
      intestinal-type gastric cancer and its precursor lesions. In contrast to the
      intestinal-type, diffuse-type gastric cancer is defined by a lack of precursor
      lesions; mutation or epigenetic silencing of the E-cadherin gene appears to be
      the key carcinogenic event. An improved understanding of the genomics of gastric
      cancer should lead to the rapid development of novel diagnostic techniques and
      molecular-based treatment strategies.

PMID- 16616345
TI  - Management of perianal Crohn's disease.

PMID- 16616346
TI  - Laryngopharyngeal reflux: a cause of faulty phonation or a faulted, phony
      diagnosis?

PMID- 16616347
TI  - Surgical fundoplication in laryngopharyngeal reflux unresponsive to aggressive
      acid suppression: a controlled study.
AB  - BACKGROUND & AIMS: In patients with persistent laryngeal symptoms despite
      aggressive proton pump inhibitor therapy, gastroesophageal reflux disease (GERD)
      continues to be implicated. The role of surgical fundoplication as the definitive
      therapy for these patients is uncertain. METHODS: In this prospective concurrent
      controlled study, 72 patients with suspected GERD-related laryngeal symptoms
      received aggressive acid-suppressive therapy. Four-month symptomatic
      nonresponders (<50% improvement) with continued laryngeal inflammation and
      normalized esophageal acid exposure were offered laparoscopic Nissen
      fundoplication. The primary outcome was symptom improvement/resolution at 1 year
      after surgery. RESULTS: Twenty-five of 72 (35%) patients remained unresponsive
      after 4 months of acid-suppressive therapy. Ten patients (40%) underwent surgical
      fundoplication (median age, 54 y; men, 4) and 15 patients (60%) continued medical
      therapy (median age, 52; men, 4). The most common laryngeal symptoms were sore
      throat, hoarseness, and cough. pH studies at 3 and 12 months were normal in all
      patients after fundoplication (median % time pH < 4, .0% and .3%; respectively).
      One of 10 (10%) patients in the surgery group reported improvement of laryngeal
      symptoms at 1 year compared with 1 of 15 in the control group (6.7%) (P = 1.0).
      Treatment of causes other than GERD improved symptoms in an additional 2 of 10
      (20%) patients in the surgical group, and 10 of 15 (66%) patients in the
      nonsurgical cohort. CONCLUSIONS: Surgical fundoplication does not improve
      laryngeal symptoms reliably in patients unresponsive to aggressive proton pump
      inhibitor therapy. The argument of low volume or intermittent reflux as the cause
      of persistent laryngeal symptoms needs to be replaced with evaluation and therapy
      for other potential non-GERD causes.

PMID- 16616348
TI  - Effect of tegaserod on esophageal pain threshold, regurgitation, and symptom
      relief in patients with functional heartburn and mechanical sensitivity.
AB  - BACKGROUND & AIMS: Tegaserod, a 5-HT4-receptor partial agonist, effectively
      treats irritable bowel syndrome with constipation. The role of tegaserod in
      functional disorders of the upper gastrointestinal (GI) tract is unclear. The
      aims of this study were to determine if tegaserod improves esophageal pain with
      mechanical and chemical stimuli, GI symptom profile, and global preference in
      patients with functional heartburn. METHODS: Patients with functional heartburn,
      as defined by Rome II criteria, underwent esophageal barostat and acid-infusion
      sensory tests. Mechanical hypersensitivity was required for entry. The baseline
      GI symptom profile was rated before treatment. Patients were blinded to treatment
      and randomly assigned to tegaserod 6 mg twice daily or placebo for 14 days, and
      crossed-over to the alternate treatment after 7 to 10 days of washout. Patients
      underwent sensory tests and rated GI symptoms after each treatment. Global
      treatment preference was completed at the end of the study. RESULTS: Forty-two
      patients (15 men, 27 women; age, 20-68 y) completed the study. The predominant
      baseline symptoms in addition to heartburn included upper-abdominal pain, upper
      abdominal discomfort, regurgitation, chest pain, early satiety, and postmeal
      bloating. Tegaserod significantly increased balloon pressure to pain (P = .04)
      and the mean (P = .002) and maximum wall tension at pain (P = .0004). Tegaserod
      did not alter pain with acid infusion. Tegaserod significantly decreased the
      frequency of occurrence of heartburn/acid reflux (P = .004), regurgitation (P =
      .048), and distress from regurgitation (P = .039). The global preference for
      tegaserod was 63.4% vs 12.2% for placebo. CONCLUSIONS: Tegaserod improved the
      esophageal pain threshold to mechanical distention, and distressing upper-GI
      symptoms in patients with functional heartburn.

PMID- 16616349
TI  - Prevalence of occult gastrointestinal bleeding in celiac disease.
AB  - BACKGROUND & AIMS: By using colorimetric tests, reports have indicated that
      occult gastrointestinal bleeding is common in celiac disease. These results
      suggest that bleeding is a significant contributor to iron deficiency in this
      disorder and imply a significant inflammatory hemorrhagic component. Both these
      concepts are contrary to previous understanding of pathology of celiac disease.
      Furthermore, colorimetric tests provide an indirect and nonspecific assessment of
      blood loss. We therefore hypothesized that an accurate, quantitative, and
      specific method for blood loss, rather than a guaiac test, might give different
      findings. We report the results of stool blood loss measurement by using such a
      method. METHODS: We measured stool blood loss directly by using 51Cr radiolabeled
      red cells in 18 consecutive patients with celiac disease who consented to the
      study, 12 with total villous atrophy and 6 with partial villous atrophy, before
      initiation of a gluten-free diet. RESULTS: Average daily blood loss exceeded 1.5
      mL in only 1 of 18 subjects. It is suspected, but unproven, that this subject had
      an alternate transient source of gastrointestinal bleeding. CONCLUSIONS:
      Colorimetric tests give a high prevalence of positive results for occult
      gastrointestinal blood loss in celiac disease, whereas the more specific and
      direct radiochromium method gives a low prevalence. These results suggest that
      bleeding is uncommon in celiac disease, and that positive results with
      colorimetric tests might be due to excess loss of intestinal cells and/or
      malabsorption of peroxidase-containing foods. Our results suggest that bleeding
      is not an important contributor to the iron deficiency often found in these
      subjects.

PMID- 16616350
TI  - Unexplained elevated serum pancreatic enzymes: a reason to suspect celiac
      disease.
AB  - BACKGROUND & AIMS: The frequency of elevated serum pancreatic enzymes in patients
      with celiac disease (CD) is unknown. The aim of this study was to evaluate the
      serum levels of pancreatic enzymes in CD patients. METHODS: Serum pancreatic
      isoamylase and lipase levels were assayed in 90 adult and 112 pediatric
      consecutive CD patients at diagnosis and after 12 months of gluten-free diet
      (GFD). Serum elastase and trypsin levels were assayed in a subgroup of adult CD
      patients. Pancreatic ultrasonography was also performed. RESULTS: Twenty-six
      adult (29%) and 29 pediatric (26%) CD patients exhibited elevated values of serum
      pancreatic amylase and/or lipase; trypsin was elevated in 69% and elastase in
      19%. The frequency of elevated serum pancreatic enzymes observed was identical in
      the patients with "typical" and "atypical" CD symptoms and in the asymptomatic
      patients. Most of the elevated values were lower than 2-fold the threshold
      limits. Elevated pancreatic enzymes were not associated with alcohol consumption,
      drug use, presence of abdominal pain, or diabetes mellitus. Abdominal ultrasound
      scan showed no abnormal findings in the pancreatic region in any of the CD
      patients. After 12 months of GFD, pancreatic amylase was elevated in 3 cases and
      lipase in 2 cases; these patients had not strictly adhered to the GFD.
      CONCLUSIONS: We demonstrated a frequency of about 25% of elevated pancreatic
      enzymes values in CD patients, including subjects without gastrointestinal
      manifestations and apparently asymptomatic subjects. The finding of elevated
      serum amylase or lipase level, in the absence of signs of pancreatic disease,
      would appear to suggest a need to screen for celiac disease.

PMID- 16616351
TI  - Natural history of intraductal papillary mucinous tumors of the pancreas:
      actuarial risk of malignancy.
AB  - BACKGROUND & AIMS: Natural history of intraductal papillary mucinous tumors of
      the pancreas (IPMTs) is unknown. Cross-sectional studies suggest that exclusive
      branch duct (BD) involvement is associated with a lower risk of carcinoma than
      main pancreatic duct (MPD) involvement. The aim of our study was to calculate
      longitudinal risk of malignant transformation of IPMT since the first sign.
      METHODS: All the patients with a diagnosis of highly probable or histologically
      proven IPMT were included. Actuarial risks of occurrence of at least low-grade
      dysplasia (>or=LGD), high-grade dysplasia (>or=HGD), or invasive carcinoma (IC)
      were calculated by Kaplan-Meier method from the first sign attributable to IPMT.
      The risks according to sex, acute pancreatitis, tumor size, and involvement of
      MPD were compared by log-rank test. RESULTS: One hundred six patients were
      included with a proven (n = 76) or probable (n = 30) IPMT. The tumor was confined
      to BD in 53 cases. Median duration since the onset of the first sign to the end
      of follow-up was 21 months (range, 0-241). Ten-year actuarial risk that IPMT
      grade was >or=LGD, >or=HGD, or IC was 67%, 49%, and 29%, respectively. The only
      morphologic risk factor of malignant transformation was involvement of MPD, with
      a 5-year actuarial risk of >or=HGD of 63% in the MPD group compared with 15% in
      the BD group (P < .001). CONCLUSIONS: Longitudinal risk of at least HGD or IC is
      time-dependent. Patients with BD IPMT present a much lower risk, justifying a
      nonoperative surveillance.

PMID- 16616352
TI  - Lymphogranuloma venereum in North America: case reports and an update for
      gastroenterologists.
AB  - BACKGROUND & AIMS: In 2003, a sharp increase in cases of lymphogranuloma venereum
      (LGV) caused by Chlamydia trachomatis in men who have sex with men was reported
      in Europe and, recently, cases of LGV have been reported in North America.
      METHODS: We reviewed 3 cases of LGV proctitis recently diagnosed in Canada.
      RESULTS: All 3 cases occurred in men who had sex with men; 2 of the patients had
      human immunodeficiency virus infection and 1 subsequently seroconverted. A delay
      in diagnosis occurred in all 3 patients: 2 patients were misdiagnosed initially
      with inflammatory bowel disease and 1 patient was treated as a case of non-LGV C
      trachomatis. CONCLUSIONS: Given the recent outbreak, gastroenterologists in
      Europe and North America need to be familiar with the diagnosis and treatment of
      LGV because it mimics inflammatory bowel disease endoscopically and
      histologically.

PMID- 16616353
TI  - Coping strategies and interpersonal support in patients with irritable bowel
      syndrome and inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Coping strategies are used to manage conflict and illness and
      can have adaptive or maladaptive effects on health status. Perceived availability
      and quality of social support also influences health status. Coping strategies
      and social support have not been well studied in irritable bowel syndrome (IBS)
      or inflammatory bowel disease (IBD). To understand their role better, coping
      strategies, social support, and psychiatric distress were assessed in patients
      with IBS and IBD and in controls. METHODS: Participants completed the Ways of
      Coping Questionnaire, the Interpersonal Support Evaluation, Symptom Checklist-90
      revised, IBS-Quality of Life (QOL), and IBD-QOL. Participants also completed the
      Toronto Alexithymia Scale and Somatosensory Amplification Scale. RESULTS: The
      study population included 55 controls, 74 IBS patients, and 48 IBD patients. The
      IBS and IBD patients had higher scores on measures of psychiatric distress,
      alexithymia, and somatosensory amplification than controls, but did not differ
      from one another. QOL scores did not differ between patients with IBS and IBD.
      Patients with IBS and IBD reported significantly less interpersonal support than
      controls. Controls identified planful problem solving as the dominant coping
      strategy whereas patients with IBS and IBD relied significantly less on planful
      problem solving and positive reappraisal and more on escape-avoidance strategies.
      CONCLUSIONS: Compared with controls, IBS and IBD patients had increased levels of
      psychiatric distress, a poorer QOL, less interpersonal support, and greater
      reliance on passive coping strategies. These data suggest that psychosocial
      disturbances are common in IBD and IBS and suggest that the observed differences
      reflect illness behavior rather than a disorder-specific process.

PMID- 16616354
TI  - The impact of increased body mass index on the clinical course of Crohn's
      disease.
AB  - BACKGROUND & AIMS: Tumor necrosis factor-alpha production in adipose tissue is
      well documented. Crohn's disease (CD) patients with increased adipose tissue may
      have more severe disease. This study evaluated overweight patients with CD to
      determine if their clinical course differs from those with a normal or low body
      mass index (BMI). METHODS: Patients at the Hospital of the University of
      Pennsylvania from 1997 to 2002 were included. Data were collected from outpatient
      records and standardized interviews. Overweight was defined as a BMI of 25 kg/m2
      or higher. The primary outcome was time to first surgery. Secondary outcomes
      included age at diagnosis, number of surgeries, and escalation of therapy.
      Patients with a BMI of 25 kg/m2 or higher at diagnosis were compared with
      patients with a BMI of less than 25 kg/m2 using statistical analyses. Survival
      analysis compared time to first surgery. RESULTS: A total of 148 patients were
      included. Forty-eight (32.4%) had a BMI of 25 kg/m2 or higher at diagnosis.
      Patients with a BMI of 25 kg/m2 or higher were older at diagnosis; 35 years vs
      22.5 years for patients with a BMI of less than 25 kg/m2 (P = .0001). The number
      of surgeries, escalation of therapy, and disease distribution did not differ
      between the 2 groups. A significant difference was found for time to first
      surgery, 252 months vs 24 months for patients with a BMI of less than 18.5 kg/m2
      vs patients with a BMI of 25 kg/m2 or higher, respectively (P = .043).
      CONCLUSIONS: CD patients with a BMI of 25 kg/m2 or higher at diagnosis were older
      at diagnosis and had a shorter time to first surgery than those with a BMI of
      less than 18.5 kg/m2. This suggests that overweight CD patients require earlier
      surgical intervention and perhaps more aggressive medical therapy.

PMID- 16616355
TI  - Cancer risks for mismatch repair gene mutation carriers: a population-based early
      onset case-family study.
AB  - BACKGROUND & AIMS: Cancer risks for mismatch repair gene mutation carriers have
      been derived almost exclusively using families ascertained owing to their strong
      cancer family history. These may be overestimates, due to analytic problems, and
      not generalizable. We estimated average cancer risks for mutations identified in
      population-based early onset colorectal cancer cases (probands) unselected for
      family history. METHODS: Data were cancer histories and mutation status (carrier,
      non-carrier, or unknown) of 17 mismatch repair gene mutation carrier probands
      with colorectal cancer diagnosed before age 45 (8 hMLH1, 4 hMSH2, 4 hMSH6, 1
      hPMS2) and their first- and second-degree relatives. We used modified segregation
      analysis theory, adjusting for the family being ascertained through the proband
      being an early onset mutation carrier. RESULTS: Eleven carrier probands (64%)
      were from families meeting the Amsterdam II criteria for hereditary nonpolyposis
      colorectal cancer. The cumulative risk for colorectal cancer (95% confidence
      interval) to age 70 was 45% (29%-62%) for men and 38% (19%-51%) for women.
      Corresponding risks were 67% (47%-84%) and 72% (48%-85%) for any hereditary
      nonpolyposis colorectal cancer-related cancer. Compared with the general
      population, colorectal cancer incidence for men was approximately 180-fold higher
      before age 50, but about the same after age 50. For women, incidence was
      approximately 100-fold higher before age 50 and 7-fold higher thereafter.
      CONCLUSIONS: For carriers of the mutations in the mismatch repair genes that
      cause early onset colorectal cancer, colorectal cancer increases rapidly until
      age 50, and the incidence decreases to general population levels at older ages.

PMID- 16616356
TI  - Novel findings in Swedish patients with MYH-associated polyposis: mutation
      detection and clinical characterization.
AB  - BACKGROUND & AIMS: Biallelic mutations in the base-excision repair gene MYH have
      recently been associated with recessive inheritance of multiple colorectal
      adenomas. An investigation and characterization of MYH mutations in Swedish
      patients were therefore carried out. METHODS: A set of 15 unrelated adenomatous
      polyposis coli (APC)-mutation negative patients from the Swedish Polyposis
      Registry was screened for germline mutations in the MYH gene. The patients were
      clinically characterized and compared with 43 APC-mutation positive probands
      diagnosed during the same period. RESULTS: Disease-causing biallelic MYH
      mutations were identified in 6 patients (40%). The mean age at diagnosis was 47.8
      years versus 34.1 years in APC-mutation positive patients (P = .015). Colorectal
      cancer at diagnosis of polyposis was present in 67% (4/6) of the patients, and
      all were right-sided, compared with only 19% versus 12.5% right-sided cancer in
      APC-mutation positive patients. Upper gastrointestinal manifestations were
      diagnosed in 1 of 5 compared with 23 of 27 in APC-mutation positive patients
      (odds ratio, 23; 95% confidence interval, 2-263; P = .0086). One family exhibited
      apparent dominant inheritance of colorectal adenomatous polyposis. Two new
      pathogenic mutations, MYH p.G175E and p.P391L, were identified. The mutations are
      argued to introduce profound changes in substrate-recognizing domains of the
      protein. CONCLUSIONS: Biallelic MYH mutations, including 2 novel mutations, were
      found in a substantial number of the patients with multiple colorectal adenomas
      who were negative for APC-mutation. The examined MYH-mutation positive patients
      were found to have higher risks of colorectal cancer at diagnosis, right-sided
      location of cancers, and a significantly lower incidence of upper
      gastrointestinal manifestations, compared with APC-mutation positive patients.

PMID- 16616357
TI  - Provider-patient in-office discussions of response to hepatitis C antiviral
      therapy and impact on patient comprehension.
AB  - BACKGROUND & AIMS: Providers need to communicate projected response rates
      effectively to enable patients with hepatitis C virus to make informed decisions
      about therapy. This study used interactional sociolinguistics (1) to evaluate how
      gastroenterologists and allied health professionals communicate information
      regarding response rates to antiviral therapy, (2) to determine how these
      discussions relate to where the patient is in the continuum of evaluation and
      treatment, (3) to assess whether patients were aligned with providers in their
      perceptions of response rates after office visits, and (4) to identify factors
      that improve provider-patient alignment. METHODS: Gastroenterologists, allied
      health professionals, and patients with hepatitis C virus were videotaped and
      audiotaped during regularly scheduled visits. Postvisit interviews were conducted
      separately with patients and providers. Visits and postvisits were transcribed
      and analyzed using validated sociolinguistic techniques. RESULTS: The phase of
      hepatitis C virus treatment shaped the benchmarks of response talk, although
      across the treatment continuum providers overwhelmingly made strategic use of
      positive statistics, providing motivation. In postvisit interviews, 55% of
      providers and patients were aligned on response rates. Patients with a favorable
      outcome and patients who asked response-related questions in the visit were more
      likely to be aligned with providers. Areas identified for improvement included
      the tendency to discuss response rates before an individualized assessment could
      be made, balancing motivation and accuracy, and assessing the patient's
      perspective before delivering any bad news, if necessary. CONCLUSIONS:
      Sociolinguistic analysis provides a powerful tool to evaluate provider-patient
      interactions and to identify ways to improve in-office communication regarding
      antiviral therapy.

PMID- 16616358
TI  - Diagnostic accuracy of magnetic resonance and endoscopic retrograde
      cholangiography in primary sclerosing cholangitis.
AB  - BACKGROUND & AIMS: To evaluate the accuracy and interobserver variability of
      magnetic resonance cholangiography (MRC) and endoscopic retrograde
      cholangiography (ERC) in the diagnosis of primary sclerosing cholangitis (PSC).
      METHODS: MRC at 1.5 T with thin- and thick-slice breath-hold technique was
      performed in 66 adult patients (median age, 44 y; 26 women) with an appropriate
      spectrum of hepatobiliary diseases. Maximum intensity projection images were
      reconstructed from the thin slices. ERC was performed within 48 hours of the MR
      examination. The reference standard of PSC diagnosis was based on a combination
      of clinical features and cholestatic biochemical profile with typical ERC and/or
      MRC abnormalities and supported by liver histology findings. Two independent
      reviewers who were unaware of final diagnoses analyzed all images
      retrospectively. RESULTS: PSC was diagnosed in 39 (59%) of 66 patients. MRC
      provided comparable and poorer depiction than ERC of extrahepatic and
      intrahepatic ducts, respectively. However, the diagnostic accuracy of ERC and MRC
      were comparable. In the MRC detection of PSC, the average sensitivity of 2
      independent readers was 80%, the specificity was 87%, and the accuracy was 83%.
      The corresponding values for ERC were a sensitivity of 89%, a specificity of 80%,
      and an accuracy of 85%. Interobserver agreement for the diagnosis of PSC was good
      (kappa = .61) for MRC and excellent (kappa = .81) for ERC. CONCLUSIONS: PSC can
      be diagnosed with high accuracy and good interobserver agreement. MRC and ERC
      performed equally well in the diagnosis of PSC when used blinded to clinical
      information.

PMID- 16616360
TI  - Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6
      mercaptopurine.

PMID- 16616361
TI  - Temporal and spatial variability of fecal indicator bacteria in the surf zone off
      Huntington Beach, CA.
AB  - Fecal indicator bacteria concentrations measured in the surf zone off Huntington
      Beach, CA from July 1998-December 2001 were analyzed with respect to their
      spatial patterns along 23 km of beach, and temporal variability on time scales
      from hourly to fortnightly. The majority of samples had bacterial concentrations
      less than, or equal to, the minimum detection limit, but a small percentage
      exceeded the California recreational water standards. Areas where coliform
      bacteria exceeded standards were more prevalent north of the Santa Ana River,
      whereas enterococci exceedances covered a broad area both north and south of the
      river. Higher concentrations of bacteria were associated with spring tides. No
      temporal correspondence was found between these bacterial events and either the
      timing of cold water pulses near shore due to internal tides, or the presence of
      southerly swell in the surface wave field. All three fecal indicator bacteria
      exhibited a diel cycle, but enterococci rebounded to high nighttime values almost
      as soon as the sun went down, whereas coliform levels were highest near the
      nighttime low tide, which was also the lower low tide.

PMID- 16616362
TI  - Alkaline unfolding and salt-induced folding of arginine kinase from shrimp
      Feneropenaeus chinensis under high pH conditions.
AB  - The structural and functional properties of arginine kinase (AK) in alkaline
      conditions in the absence or presence of salt have been investigated. The
      conformational changes of AK during alkaline unfolding and salt-induced folding
      at alkaline pH were monitored using intrinsic fluorescence emission, binding of
      the fluorescence probe 1-anilino-8-naphthalenesulfonate and circular dichroism.
      The results for the alkaline unfolded enzyme showed that much lower pH (11.0) was
      required to cause the complete loss of AK activity than was required to cause an
      obvious conformational change of the enzyme. Compared with the completely
      unfolded state in 5M urea, the high pH denatured enzyme had some residual
      secondary and tertiary structure even at pH 13.0. Increasing the ionic strength
      by adding salt at pH 12.75 resulted in the formation of a relatively compact
      tertiary structure and a little new secondary structure with hydrophobic surface
      enhancement. These results indicate that the partially folded state formed under
      alkaline conditions may have similarities to the molten globule state which is
      compact, but it has a poorly defined tertiary structure and a native-like
      secondary structure.

PMID- 16616363
TI  - Thermophysical properties of aqueous and frozen states of BSA/water/Tris systems.
AB  - In the modelling and the optimization of pharmaceutical protein freeze-drying
      processes, thermophysical properties values of the formulation in frozen or in
      liquid states are necessary in order to determine the optimal operating
      conditions (temperature, pressure) of the two steps (sublimation, desorption)
      drying diagramme and the optimal storage conditions of the final freeze-dried
      product. The most important thermophysical properties of BSA/water/Tris system
      buffered with Tris-HCl (5%, w/w) at pH 7, a standard formulation largely used in
      industrial freeze-drying process of pharmaceutical proteins, are reported in this
      paper. The state diagram of this formulation was determined by modulated
      temperature differential scanning calorimetry (MTDSC) and, then the vitreous
      transition temperatures were interpreted as a function of water content by the
      Gordon-Taylor equation. The same technique was used to experimentally determine
      the heat capacity of the BSA/water frozen system. Moreover, the transient hot
      wire probe method was used to measure the thermal conductivity of the frozen
      system as a function of temperature. It proved that the thermal conductivity and
      the apparent heat capacity values for this dilute formulation were reasonably
      close to the values for the pure water/ice system. Sorption isotherms data were
      also measured by two different methods-the equilibrium with saturated salts
      solutions and also the controlled humidity oven. Water vapour sorption data were
      finally correlated by the three parameters Guggenheim, Anderson, De Boer (GAB)
      equation.

PMID- 16616365
TI  - Detection of a specific DNA sequence by electrophoresis through a molecularly
      imprinted polymer.
AB  - To develop a simple and inexpensive DNA detection method, we prepared a
      molecularly imprinted polymer (MIP) gel for recognizing a specific double
      stranded DNA (dsDNA) target sequence in MIP gel electrophoresis (MIPGE). During
      MIPGE, migration of the target sequence of dsDNA should be hindered by the
      capture effect of the binding sites in the MIP gel. This migration hindrance of
      target dsDNA was determined by plotting the relationship between the migration
      distance in the MIP gel and that in polyacrylamide gel, commonly used in gel
      electrophoresis. Using this plot, detection of a target dsDNA from a mixture of
      different-sized dsDNA fragments was achieved. Moreover, we found the detection
      method successfully distinguished between a target and its base-pair substitutes.
      These results suggest that MIPGE could be employed for detection of a target
      dsDNA sequence.

PMID- 16616364
TI  - Use of chitosan bandage to prevent fatal infections developing from highly
      contaminated wounds in mice.
AB  - HemCon bandage is an engineered chitosan acetate preparation used as a hemostatic
      control dressing, and its chemical structure suggests that it should also be
      antimicrobial. We tested its ability to rapidly kill bacteria in vitro and in
      mouse models of infected wounds. We used the Gram-negative species Pseudomonas
      aeruginosa and Proteus mirabilis and the Gram-positive Staphylococcus aureus that
      had all been stably transduced with the entire bacterial lux operon to allow in
      vivo bioluminescence imaging. An excisional wound in Balb/c mice was inoculated
      with 50-250 million cells followed after 30 min by application of HemCon bandage,
      alginate sponge bandage, silver sulfadiazine cream or no treatment. HemCon was
      more adhesive to the wound and conformed well to the injury compared to alginate.
      Animal survival was followed over 15 days with observations of bioluminescence
      emission and animal activity daily. Chitosan acetate treated mice infected with
      P. aeruginosa and P. mirabilis all survived while those receiving no treatment,
      alginate and silver sulfadiazine demonstrated 25-100% mortality. Chitosan acetate
      was much more effective than other treatments in rapidly reducing bioluminescence
      in the wound consistent with its rapid bactericidal activity in vitro as well as
      its light-scattering properties. S. aureus formed only non-lethal localized
      infections after temporary immunosuppression of the mice but HemCon was again
      more effective in reducing bioluminescence. The data suggest that chitosan
      acetate rapidly kills bacteria in the wound before systemic invasion can take
      place, and is superior to alginate bandage and silver sulfadiazine that may both
      encourage bacterial growth in the short term.

PMID- 16616366
TI  - Inducing hepatic differentiation of human mesenchymal stem cells in pellet
      culture.
AB  - Extensive cell-cell or cell-matrix interaction in three-dimensional (3D) culture
      is important for the maintenance of adult hepatocyte function and the maturation
      of hepatic progenitors. However, although there is significant interest in
      inducing the transdifferentiation of adult stem cells into the hepatic lineage,
      very few studies have been conducted in a 3D culture configuration. The aim of
      this study is to investigate the differentiation of mesenchymal stem cells (MSC)
      into hepatocytes in a pellet configuration, with or without the presence of small
      intestinal submucosa (SIS). After 4 weeks of differentiation with growth factors
      bFGF, HGF, and OsM, we obtained hepatocyte-like cells that expressed a subset of
      hepatic genes, secreted albumin and urea, stored glycogen, and showed inducible
      CYP3A4 mRNA levels. When these cells were implanted into livers of hepatectomized
      rats, they secreted human albumin into the bloodstream. The hepatic
      differentiation of MSC was faster in cell pellets without SIS. The plausible
      explanations for this finding may be related to the mass transport issues of the
      two different pellets and the role of cell-cell contact over cell-matrix
      interactions. The findings of this study should help in the design of optimal
      culture configurations for efficient hepatic differentiation of adult stem cells.

PMID- 16616367
TI  - Urgent medical assessment after child sexual abuse.
AB  - BACKGROUND: Immediate medical assessment has been recommended for children after
      sexual abuse to identify physical injuries, secure forensic evidence, and provide
      for the safety of the child. However, it is unclear whether young children seen
      urgently within 72 hours of reported sexual contact would have higher frequencies
      of interview or examination findings as compared to those seen non-urgently or
      whether forensic findings would be affected by child characteristics, type of
      reported contact, or later events. DESIGN/SETTING: We evaluated 190 consecutive
      cases of children under 13 years of age urgently referred during a 5-year period
      in 1998-2003 to a community child advocacy center and compared them to those non
      urgently referred with regard to their physical examination findings, any
      sexually transmitted infections or forensic evidence, gender, pubertal
      development, type of contact, reported ejaculation, later bathing or changing
      clothes, time to examination, and gender, age and relationship of alleged
      perpetrator. RESULTS: Children seen urgently were younger and had less frequent
      CPS involvement, more disclosures, and more positive physical examinations, and
      had more contact with older perpetrators than those seen non-urgently. Overall,
      most children were female and had normal or non-specific physical examinations.
      Certain case characteristics were predictive of evidence isolation in the 9% who
      had positive forensic evidence identified. Semen or sperm was identified from
      body swabs only from non-bathed, female children older than 10 years of age or on
      clothing or objects. CONCLUSIONS: Female children over 10 years old who report
      ejaculation or genital contact without bathing have the highest likelihood of
      positive examinations or forensic evidence. While there are other potential
      benefits of early examination, physicians seeking to identify forensic evidence
      should consider the needs of the child and other factors when determining the
      timing of medical assessment after sexual abuse.

PMID- 16616368
TI  - Dual function of fish hepcidin: response to experimental iron overload and
      bacterial infection in sea bass (Dicentrarchus labrax).
AB  - The role of hepcidin in iron metabolism regulation and bacterial infection has
      been the focus of recent attention. However, in spite of the growing number of
      hepcidin genes known from different organisms, little is known about its putative
      dual function in fish. The aim of this study was to characterize the sea bass
      hepcidin gene and to study its role in iron metabolism and infection. The novel
      sea bass hepcidin gene was found to be organized into two introns and three exons
      with several copies present in the genome. The transcript showed a constitutive
      low basal expression being mainly expressed in liver and encoding a putative 85
      residues long peptide. Fish were submitted either to iron status modulation or
      bacterial infection and the hepcidin transcript levels were analysed along with a
      number of other parameters. Liver hepcidin expression was found to increase in
      both the iron-overloaded and infected fish, while in the iron-deficient fish no
      alteration in expression levels was detected. These results point to the
      evolutionary conservation of hepcidin's dual functions.

PMID- 16616369
TI  - Quantitative structure-activity relationship modeling of polycyclic aromatic
      hydrocarbon mutagenicity by classification methods based on holistic theoretical
      molecular descriptors.
AB  - Various polycyclic aromatic hydrocarbons (PAHs), ubiquitous environmental
      pollutants, are recognized mutagens and carcinogens. A homogeneous set of
      mutagenicity data (TA98 and TA100,+S9) for 32
      benzocyclopentaphenanthrenes/chrysenes was modeled by the quantitative structure
      activity relationship classification methods k-nearest neighbor and
      classification and regression tree, using theoretical holistic molecular
      descriptors. Genetic algorithm provided the selection of the best subset of
      variables for modeling mutagenicity. The models were validated by leave-one-out
      and leave-50%-out approaches and have good performance, with sensitivity and
      specificity ranges of 90-100%. Mutagenicity assessment for these PAHs requires
      only a few theoretical descriptors of their molecular structure.

PMID- 16616370
TI  - Transfer of nodularin to three-spined stickleback (Gasterosteus aculeatus L.),
      herring (Clupea harengus L.), and salmon (Salmo salar L.) in the northern Baltic
      Sea.
AB  - Nodularin (NODLN) is a hepatotoxin produced by the cyanobacterium Nodularia
      spumigena, which occurs regularly in the Baltic Sea. The primary aim of this
      study was to study the transfer of NODLN to three-spined stickleback
      (Gasterosteus aculeatus L.), herring (Clupea harengus membras L.), and salmon
      (Salmo salar L.), which were caught from the northern Baltic Sea between August
      2002 and August 2003. Liquid chromatography mass spectrometry (LC-MS) was used
      for NODLN analysis. NODLN was found in both herring (0-90 microgkg(-1)dw) and
      three-spined sticklebacks samples (2.8-700 microgkg(-1)dw). The recovery for the
      spiked stickleback samples in vitro was 28%. Only 1 salmon of a total of 10
      contained a small amount of NODLN (10 microgkg(-1)dw). However, the high
      concentrations in individual stickleback suggest that possible transfer to higher
      trophic levels deserves more research.

PMID- 16616371
TI  - Patterns of serum PCDD/Fs affected by vegetarian regime and consumption of local
      food for residents living near municipal waste incinerators from Taiwan.
AB  - The aim of this study was to evaluate possible factors affecting serum
      polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) levels of people
      living near municipal waste incinerators (MWIs). We selected 19 MWIs in Taiwan
      and collected 1708 serum samples from residents 18-65 years old who had lived
      within 5 km of one of the selected MWIs for at least 5 years. The samples were
      analyzed using a standardized study protocol to assure comparability of the
      concentrations from 17 PCDD/F congeners. The results suggested that a vegetarian
      regimen was a protective factor to avoid serum PCDD/F accumulation in the
      subjects. In addition, the current data seemed to support the hypothesis that
      serum PCDD/F levels of residents living near MWIs are related to they consumed
      the locally grown or cultivated vegetable and animal foods, such as poultry
      products near the MWIs. Our results can be used to create guidelines for
      preventing excessive PCDD/F accumulation from eating animal and vegetable foods
      grown near MWIs.

PMID- 16616372
TI  - The effect of ageing on the bioaccessibility and fractionation of cadmium in some
      typical soils of China.
AB  - Ingestion of contaminated soil has been recognized as an important exposure
      pathway of cadmium (Cd) for humans, especially for children through outdoor hand
      to-mouth activities. The effect of ageing process following the input of Cd into
      soil on the bioaccessibility of Cd in five typical soils of China was
      investigated using physiologically based in vitro test in this study. A
      sequential extraction procedure was employed with attempt to identify the
      bioaccessible fraction(s) of Cd in soils. The bioaccessibility of Cd in strongly
      acidic (approximately pH 4.5) soils reached nearly steady levels (76.5-76.9% and
      52.0-52.6% in the gastric and small intestinal phases, respectively) after a
      sharp decline in the first week of ageing. In contrast, the bioaccessibility of
      Cd in higher pH (>6.0) soils was found to be much lower (53.3-72.7% and 29.9
      43.4% in gastric and small intestinal phases, respectively) and took 2 weeks of
      ageing to reach steady levels. The freshly spiked Cd was more labile than native
      Cd. The main proportion of spiked Cd was found in exchangeable Cd which was
      higher in strongly acidic soils (68.6-71.8%) than in higher pH soils (53.4-61.4%)
      at day 120 after a sharp decline to the nearly steady state in the first 1 and 2
      weeks, respectively. Significant correlations between Cd bioaccessibility and
      either water soluble and exchangeable Cd individually, or the sum of water
      soluble and exchangeable Cd throughout the incubation period for all soils,
      indicate that these forms of Cd are likely to constitute the main proportion of
      bioaccessible Cd in soils.

PMID- 16616373
TI  - Insights into the role of nucleotide-dependent conformational change in
      nitrogenase catalysis: Structural characterization of the nitrogenase Fe protein
      Leu127 deletion variant with bound MgATP.
AB  - In the present work, determination of the structure of the nitrogenase Leu 127
      deletion variant Fe protein with MgATP bound is presented, along with density
      functional theory calculations, to provide insights into the roles of MgATP in
      the nitrogenase reaction mechanism. Comparison of the MgATP-bound structure of
      this Fe protein to the nucleotide-free form indicates that the binding of MgATP
      does not alter the overall structure of the variant significantly with only small
      differences in the conformation of amino acids in direct contact with the two
      bound MgATP molecules being seen. The earlier observation of splitting of the
      [4Fe-4S] cluster into two [2Fe-2S] clusters was observed to be unaltered upon
      binding MgATP. Density functional theory was used to probe the assignment of
      ligands to the two [2Fe-2S] rhombs. The Mg(2+) environment in the MgATP-bound
      structure of the Leu127 deletion Fe protein is similar to that observed for the
      Fe protein in the nitrogenase Fe protein: MoFe protein complex stabilized by
      MgADP and tetrafluoroaluminate suggesting that large scale conformational change
      implicated for the Fe protein may not be mediated by changes in the Mg(2+)
      coordination. The results presented here indicated that MgATP may enhance the
      stability of an open conformation and prohibit intersubunit interactions, which
      have been implicated in promoting nucleotide hydrolysis. This could be critical
      to the tight control of MgATP hydrolysis observed within the nitrogenase complex
      and may be important for maintaining unidirectional electron flow toward
      substrate reduction.

PMID- 16616374
TI  - Inactivating mutations of G protein-coupled receptors and diseases: structure
      function insights and therapeutic implications.
AB  - Since the discovery of the first rhodopsin mutation that causes retinitis
      pigmentosa in 1990, significant progresses have been made in elucidating the
      pathophysiology of diseases caused by inactivating mutations of G protein-coupled
      receptors (GPCRs). This review aims to compile the compelling evidence
      accumulated during the past 15 years demonstrating the etiologies of more than a
      dozen diseases caused by inactivating GPCR mutations. A generalized
      classification scheme, based on the life cycle of GPCRs, is proposed. Insights
      gained through detailed studies of these naturally occurring mutations into the
      structure-function relationship of these receptors are reviewed. Therapeutic
      approaches directed against the different classes of mutants are being developed.
      Since intracellular retention emerges as the most common defect, recent
      progresses aimed at correcting this defect through membrane permeable
      pharmacological chaperones are highlighted.

PMID- 16616375
TI  - Determination of glucose metabolites in stored erythrocytes and in erythrocytes
      from patients with thalassemia by analytical isotachophoresis.
AB  - Glycolysis is for some cells, such as erythrocytes, neutrophil granulocytes and
      many cancer cells, the only or most important source of energy (ATP) production.
      Based on previous studies we developed an isotachophoretic (ITP) method which
      allows, in principle, the simultaneous determination of all metabolites of
      glycolysis. Since glucose metabolites are small anions, mobility of some of them
      may overlap in isotachophoresis and, therefore, partial mixed zones are
      generated. By variation of the leading/terminating system, however, it is
      possible to separate the compounds of interest. In this communication, we
      describe a method for analysis of glucose metabolites in erythrocytes from
      healthy donors during storage in blood bags, and from patients with thalassemia,
      with special respect to intracellular 2,3 bisphosphoglycerate, lactate and
      ATP/ADP. The well known characteristic changes of glycolysis in erythrocytes
      during blood storage and in erythrocytes from thalassemia patients, which are
      often analysed by separate enzymatic assays, could be confirmed with this
      isotachophoretic procedure. The method is currently adapted for analysis of
      glycolysis in neutrophil granulocytes and cancer cells which requires some
      modifications of sample preparation and performance of the isotachophoretic
      analysis.

PMID- 16616376
TI  - Detection of depression in women of child-bearing age in non-Western cultures: a
      comparison of the Edinburgh Postnatal Depression Scale and the Self-Reporting
      Questionnaire-20 in Mongolia.
AB  - BACKGROUND: This study assesses, for the first time, the validity and internal
      reliability of the Edinburgh Post Natal Depression Scale (EPDS) and the WHO Self
      Reporting Questionnaire 20-item version (SRQ-20) in detecting depression in
      Mongolian women of reproductive age. METHODS: 100 women age recruited from two
      psychiatric units specialising in depression (n = 55) and three community-based
      child immunisation clinics (n = 45) in Ulaanbataar, Mongolia, were formally
      psychiatrically assessed by a clinician and by administering the revised Clinical
      Interview Schedule (CIS-R). Each woman also completed the EPDS and SRQ-20.
      RESULTS: Ninety four women provided complete data and identical optimal cut-off
      points for both the EPDS (11.5) and SRQ-20 (8.5) were determined against both the
      psychiatrist's and CIS-R based diagnosis using standard validation parameters. On
      all parameters the SRQ-20 performed better than the EPDS. The sensitivity of the
      SRQ-20 in detecting depression was 93% and the specificity 97% against the
      psychiatrist's diagnosis. Internal reliability was satisfactory. LIMITATIONS: The
      use of a mixed clinical and community sample for validation, and a single
      psychiatrist may limit the generalisability of these results. CONCLUSIONS: The
      SRQ-20 performed well and better than the EPDS in detecting depression in this
      group of Mongolian women.

PMID- 16616377
TI  - Differential expression of human leukocyte antigen-G (HLA-G) messenger RNAs and
      proteins in normal human prostate and prostatic adenocarcinoma.
AB  - Human leukocyte antigen-G (HLA-G) is a major histocompatibility complex class Ib
      gene expressed in normal organs and in some tumors. The glycoproteins encoded by
      this gene are best known for their immunosuppressive properties. Because isoform
      specific expression of HLA-G in male reproductive organs has not been reported,
      we investigated HLA-G1, -G2, -G5, -G6 mRNAs and proteins in four-to-five samples
      of normal prostate glands, prostates with benign prostatic hyperplasia and
      prostate adenocarcinomas using RT-PCR and immunohistochemistry. All tissues
      contained HLA-G1, -G2, -G5 and -G6 specific mRNAs, but only HLA-G5 protein was
      detectable. In normal prostate glands, HLA-G5 protein was prominent in the
      cytoplasm of tubuloglandular epithelia and in glandular secretions. Staining was
      reduced in samples of benign prostatic hyperplasia but remained localized to the
      cytoplasm of glandular epithelia and secretions. In prostatic adenocarcinomas,
      HLA-G5 protein was detectable mainly in the secretions. Thus, HLA-G5 but not HLA
      G1, -G2 or -G6 is produced in the normal prostate and is present in prostatic
      secretions. In addition, normal cellular localization is disturbed in benign and
      malignant prostatic adenocarcinomas. The results are consistent with this
      molecule may influencing female immune receptivity to sperm and suggest that such
      immunosuppression could be disturbed in men with prostatic adenocarcinomas.

PMID- 16616378
TI  - Comparative evaluation of RT-PCR, nucleic acid sequence-based amplification
      (NASBA) and real-time RT-PCR for detection of noroviruses in faecal material.
AB  - Using different primer and probe sets, RT-PCR, NASBA and TaqMan RT-PCR molecular
      methods were compared to detect NoV GII in 13 clinical stool samples. The RT-PCR
      results observed by gel electrophoresis (Ando, Kageyama and Anderson
      amplification and probe systems), dot blot hybridization (Ando and Kageyama) and
      real-time TaqMan assay (Ando and Kageyama) were shown to be consistent and
      reproducible for the detection of NoV GII. Whereas, the NASBA assay using Ando
      primers showed some reproducibility discrepancies. Detection limits of the NoV
      GII/Kageyama system were found to be equal or significantly higher than the Ando
      system. Real-time TaqMan RT-PCR assay showed similar detection limits to that of
      NASBA with the Kageyama amplification and detection system, while it was 1log
      less sensitive than the Ando system. In a clinical context, RT-PCR, NASBA and
      real-time TaqMan RT-PCR methods using undiluted samples were all suitable for the
      detection of NoV GII, however the NASBA assay provided less consistent signals.
      The NoV GII Kageyama real-time TaqMan RT-PCR assay was reliable with a high
      analytical sensitivity and has shown the capability of detecting one genomic
      equivalent copy.

PMID- 16616379
TI  - LRRK2 in Parkinson's disease: protein domains and functional insights.
AB  - Parkinson's disease (PD) is the most common motor neurodegenerative disease.
      Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) have been
      linked recently with autosomal-dominant parkinsonism that is clinically
      indistinguishable from typical, idiopathic, late-onset PD. Thus, the protein
      LRRK2 has emerged as a promising therapeutic target for treatment of PD. LRRK2 is
      extraordinarily large and complex, with multiple enzymatic and protein
      interaction domains, each of which is targeted by pathogenic mutations in
      familial PD. This review places the PD-associated mutations of LRRK2 in a
      structural and functional framework, with the ultimate aim of deciphering the
      molecular basis of LRRK2-associated pathogenesis. This, in turn, should advance
      our understanding and treatment of familial and idiopathic PD.

PMID- 16616380
TI  - Cadmium toxicity to two marine phytoplankton under different nutrient conditions.
AB  - Cd accumulation and toxicity in two marine phytoplankton (diatom Thalassiosira
      weissflogii and dinoflagellate Prorocentrum minimum) under different nutrient
      conditions (nutrient-enriched, N- and P-starved conditions) were examined in this
      study. Strong interactions between the nutrients and Cd uptake by the two algal
      species were found. Cd accumulation as well as N and P starvation themselves
      inhibited the assimilation of N, P, and Si by the phytoplankton. Conversely, N
      starvation strongly inhibited Cd accumulation but no influence was observed under
      P starvation. However, the Cd accumulation difference between nutrient-enriched
      and N-starved cells was smaller when [Cd(2+)] was increased in the medium,
      indicating that net Cd accumulation was less dependent on the N-containing
      ligands at high-Cd levels. As for the subcellular distribution of the accumulated
      Cd, most was distributed in the insoluble fraction of T. weissflogii while it was
      evenly distributed in the soluble and insoluble fractions of P. minimum at low-Cd
      levels. A small percentage of cellular Cd (<15%) was adsorbed on the cell surface
      for both algae at the lowest [Cd(2+)], which increased when the [Cd(2+)]
      increased. Cd toxicity in phytoplankton was quantified as depression of growth
      and maximal photosynthetic system II quantum yield, and was correlated with the
      [Cd(2+)], intracellular Cd concentration, and Cd concentrations in the cell
      surface-adsorbed, soluble, and insoluble fractions. According to the estimated
      median inhibition concentration (IC50) based on the different types of Cd
      concentration, the toxicity difference among the different nutrient-conditioned
      cells was the smallest when the Cd concentration in the soluble fraction was
      used, suggesting that it may be the best predictor of Cd toxicity under different
      nutrient conditions.

PMID- 16616381
TI  - Genotoxic and stress inductive potential of cadmium in Xenopus laevis larvae.
AB  - The present investigation evaluates the toxic potential of Cd in larvae of the
      frog Xenopus laevis after 12 days of exposure to environmentally relevant
      contamination levels, close to those measured in the river Lot (France). Several
      genotoxic and detoxification mechanisms were analyzed in the larvae: clastogenic
      and/or aneugenic effects in the circulating blood by micronucleus (MN) induction,
      metallothionein (MT) production in whole larvae, gene analyses and Cd content in
      the liver and also in the whole larvae. The results show: (i) micronucleus
      induction at environmental levels of Cd contamination (2, 10, 30 microgL(-1));
      (ii) an increased and concentration-dependent quantity of MT in the whole
      organism after contamination with 10 and 30 microgCdL(-1) (a three- and six-fold
      increase, respectively) although no significant difference was observed after
      contamination with 2 microgCdL(-1); (iii) Cd uptake by the whole organism and by
      the liver as a response to Cd exposure conditions; (4) up-regulation of the genes
      involved in detoxification processes and response to oxidative stress, while
      genes involved in DNA repair and apoptosis were repressed. The results confirm
      the relevance of the amphibian model and highlight the complementarity between a
      marker of genotoxicity, MT production, bioaccumulation and genetic analysis in
      the evaluation of the ecotoxicological impact.

PMID- 16616382
TI  - Plasmodia express two threonine-peptidase complexes during asexual development.
AB  - Threonine-peptidases of the T1-family are multi-subunit complexes with broad
      substrate specificity. In eukaryotes, at least 14 genes encode subunits of the
      prototypic T1 threonine-peptidase, the proteasome. The proteasome determines the
      turnover of most proteins and thereby plays a fundamental role in diverse
      processes such as protein quality control, signal transduction, and cell cycle
      regulation. While eukaryotes and archaea possess a proteasome, bacteria generally
      express a second member of the T1-family, the proteasomal predecessor ClpQ/hslV
      that has a similar structure but is encoded by only one gene. The plasmodial
      genome is an exception because it encodes proteasomal subunits as well as a
      ClpQ/hslV-orthologe (Plasmodium falciparum-hslV; PfhslV). Structure, expression,
      and function of both types of peptidase-complex in P. falciparum are presently
      unknown. Our aim was to analyze both the coding sequences and derived proteins of
      both peptidase-complexes because highly specific and potent inhibitors can be
      designed against this class of enzymes. The proteasome was found expressed
      throughout the cell cycle, whereas PfhslV was detectable in schizonts and
      merozoites only. Treatment of P. falciparum with the threonine-peptidase
      inhibitor epoxomicin blocked two of three catalytically active proteasome
      subunits. This led to the accumulation of ubiquitinated proteins and, finally, to
      parasite death. In conclusion, we provide the first functional analysis of
      plasmodial threonine-peptidase-complexes and identify a lead compound for the
      development of a novel class of antimalarial drugs.

PMID- 16616383
TI  - Multiple accessory pathways, dual AV nodal physiology, non-compacted myocardium
      and patent foramen ovale in a patient with Ebstein's anomaly: report of a case.
AB  - Ebstein's anomaly is a rare congenital cardiac disease initially described by
      Wilhelm Ebstein in 1866. The primary pathology involves significant apical
      displacement of the septal tricuspid valve leaflet and the presence of a
      redundant, elongated, anterior tricuspid valve leaflet. This congenital
      malformation has multiple known associated morphological and electrophysiological
      cardiac pathologies. In the present article, we report, to the best of our
      knowledge for the first time in the literature, a case of Ebstein's anomaly with
      multiple accessory bypass tracts, dual AV nodal physiology, non-compacted left
      ventricular myocardium and a patent foramen ovale. Indeed, complete evaluation of
      the left heart is required in cases of Ebstein's anomaly to accurately assess
      left ventricular myocardial structure.

PMID- 16616384
TI  - Following the biochemical and morphological changes of Bacillus atrophaeus cells
      during the sporulation process using Bioaerosol Mass Spectrometry.
AB  - Bioaerosol Mass Spectrometry (BAMS), a real-time single cell analytical
      technique, was used to follow the biochemical and morphological changes within a
      group of Bacillus atrophaeus cells by measuring individual cells during the
      process of sporulation. A mutant of B. atrophaeus that lacks the ability to
      produce dipicolinic acid (DPA) was also analyzed. Single cell aerodynamic sizing
      was used to follow gross morphological changes, and chemical analysis of single
      cells by mass spectrometry was used to follow some biochemical changes of B.
      atrophaeus cells during endospore formation.

PMID- 16616385
TI  - Quantification of Vibrio penaeicida, the etiological agent of Syndrome 93 in New
      Caledonian shrimp, by real-time PCR using SYBR Green I chemistry.
AB  - Shrimp farming is a small but growing industry in New Caledonia. Since 1993,
      "Syndrome 93" has been affecting New Caledonian shrimp farming industry every
      cold season, causing severe epizootic mortalities in grow-out ponds and
      significant losses. Highly pathogenic strains of Vibrio penaeicida are considered
      the etiological agent of the disease in Litopenaeus stylirostris. On one hand,
      studies demonstrated that healthy shrimp may carry V. penaeicida for weeks with a
      high overall prevalence, regardless of any seasonal pattern or temperature
      conditions. On the other hand, larvae are free of V. penaeicida and are also
      resistant to experimental infection. V. penaeicida is frequently detected in
      incoming water pumped from the bays, which was shown, by a molecular typing
      study, to be the infectious source. This particular epidemiological pattern
      highlights the major role of the factors that trigger and aggravate the disease
      in grow-out ponds, where shrimp populations carry the pathogen all year round. In
      order to gain a better understanding of "Syndrome 93" epidemiology,
      quantification of V. penaeicida both in shrimp and the shrimp farm ecosystem is
      necessary. This article describes the steps in the successful development of a
      real-time PCR quantification assay of V. penaeicida in shrimp haemolymph,
      seawater (from ponds or bays) and sediment pore water, including the choice of an
      accurate extraction technique. The entire detection method; including sample
      processing, DNA extraction and real-time PCR amplification, can be completed
      within 4 h.

PMID- 16616386
TI  - Evaluation of the use of conductimetry for the rapid and precise measurement of
      Salmonella spp. growth rates.
AB  - The growth rates of 14 Salmonella serovars in tryptone soy broth plus yeast
      extract (TSBYE) were estimated using conventional plating techniques and indirect
      conductimetry using a Don Whitley RABIT system. Both methods gave identical
      results for the maximum specific growth rate (mumax) P>0.05. However, using the
      conductimetric method, mumax for a single serovar was determined in less than 7
      h, whereas the conventional method required an additional 24 h. In addition, the
      conductimetric method was considerably more precise, much less labour-intensive
      and required the use of considerably less consumables. Using conductimetry, a
      trained operator could accurately determine mumax for 24 serovars in 3 working
      days, but only one serovar using the conventional plate counting technique.
      Hence, the use of conductimetry can markedly increase the precision and accuracy
      of mumax determinations by allowing a very significant increase in the number of
      results obtained and in their precision. The data generated will allow the
      development of better mathematical growth models. The method can also be used to
      compare growth media and conditions and hence rapidly optimise detection
      protocols for this pathogen.

PMID- 16616387
TI  - Proposal for the delineation of the nodal CTV in the node-positive and the post
      operative neck.
AB  - BACKGROUND AND PURPOSE: In 2003, a panel of experts published a set of consensus
      guidelines regarding the delineation of the neck node levels (Radiother Oncol,
      2003; 69: 227-36). These recommendations were applicable for the node-negative
      and the N1-neck, but were found too restrictive for the node-positive and the
      post-operative neck. PATIENTS AND METHODS: In this framework, using the previous
      recommendations as a backbone, new guidelines have been proposed taking into
      account the specificities of the node-positive and the post-operative neck.
      RESULTS: Inclusion of the retrostyloid space cranially and the supra-clavicular
      fossa caudally is proposed in case of neck nodes (defined radiologically or on
      the surgical specimen) located in levels II, and IV or Vb, respectively. When
      extra-capsular rupture is suspected (on imaging) or demonstrated on the
      pathological specimen, adjacent muscles should also be included in the CTV. For
      node(s) located at the boundary between contiguous levels (e.g. levels II and
      Ib), these two levels should be delineated. In the post-operative setting, the
      entire 'surgical bed' should be included. Last, the retropharyngeal space should
      be delineated in case of positive neck from pharyngeal tumors. CONCLUSIONS: The
      objective of the manuscript is to give a comprehensive description of the new set
      of guidelines for CTV delineation in the node-positive neck and the post
      operative neck, with a complementary atlas of the new anatomical structures to be
      included.

PMID- 16616388
TI  - Consideration about axillary nodes and arm position.

PMID- 16616389
TI  - Biofilm formation and the survival of Salmonella Typhimurium on parsley.
AB  - Although several studies provide evidence that the formation of biofilms by human
      pathogens on plant tissue is possible, to date there is no direct evidence that
      biofilms enhance the resistance of plant-associated pathogens to disinfectants or
      biocides. We hypothesized that biofilm formation would enhance the adhesion and
      survival of Salmonella on leafy vegetables. To test our hypothesis, we compared
      the adhesion and persistence of Salmonella Typhimurium and its biofilm-deficient
      isogenic mutant. Following inoculation of parsley and rinsing with water or
      chlorine solution, both strains had similar survival properties, and up to 3-log
      reduction were observed, depending on chlorine concentration. This indicates that
      the biofilm matrix of Salmonella likely does not play a significant role in
      initial adhesion and survival after disinfection. After a week of storage the
      biofilm producing strain survived chlorination significantly better than the
      biofilm-deficient mutant. However, the recovery of the mutant was still elevated,
      indicating that although the biofilm matrix has a role in persistence of
      Salmonella after chlorination treatment of parsley, this is not the most
      important mechanism, and other mechanisms, probably the ability to penetrate the
      plant tissue or the pre-existing biofilms, or production of different
      polysaccharides other than cellulose, provide the protection.

PMID- 16616390
TI  - Highly effective inhibition of Akabane virus replication by siRNA genes.
AB  - Since 2002 there has been a rise in arthrogryposis/hydranencephaly (AGH)
      incidence in Israel, caused by Akabane (AKA) and, possibly, Aino viruses. To test
      the ability to control the disease, three siRNA genes targeted to the S genome
      segment were designed and prepared in the form of siRNA cassettes. For the design
      all published S segment were aligned and two conserved target sequences with 100%
      homology were chosen. A third conserved target that was found exhibited only one
      base change found in the two Australian isolates and was also designed and
      tested. It was demonstrated that cells transfected with single siRNA genes showed
      99% inhibition, as measured by real-time RT-PCR, virus titration and
      immunofluorescence. When cells were transfected with all three genes together the
      inhibition levels were increased and reached almost 100%.

PMID- 16616391
TI  - Distribution and heterogeneity of small ruminant lentivirus envelope subtypes in
      naturally infected French sheep.
AB  - Small ruminants lentiviruses (SRLV) nucleotide sequences spanning the V1V2
      variable regions of the env gene were amplified by nested-PCR from 38 blood
      samples collected from 16 naturally infected sheep flocks in France. For the
      rapid SRLV group determination of field isolates, the PCR-amplified fragments
      were subjected to a SRLV-adapted heteroduplex mobility assay (HMA). All viral
      sequences were clearly assignable to the SRLV group B by HMA analysis. Twenty
      seven SRLV isolates were selected for DNA sequence analysis. In each case,
      nucleotide comparison and phylogenetic analyses confirmed the genetic
      relationships inferred by HMA. Six SRLV isolates belonged to subtype B1, and 21
      pertained to subtype B2, one flock being infected with both subtypes. Subtypes B1
      and B2 were found with different frequencies and geographic spread, but exhibited
      similar genetic diversities. These results give a more complete picture of the
      distribution and heterogeneity of SRLV env subtypes in sheep and confirmed that
      multiple interspecies transmission occurred in the past. Furthermore, HMA
      appeared to be a rapid and reliable method to differentiate caprine arthritis
      encephalitis virus from maedi-visna virus.

PMID- 16616392
TI  - [Non-invasive urodynamics in male patient].
AB  - PURPOSE: Pressure-flow studies are currently recognized as the criterion standard
      to quantify urethral obstruction and its consequence on detrusor contractility.
      These tests have some disadvantages: they are invasive, time-consuming and
      expensive and entail risk of disease for the patient. Less invasive methods have
      been proposed to give the same results without the disadvantages. In this study,
      we conducted a critical analysis of the devices and techniques and their results.
      METHOD: After a brief reminder of the general behavior of the flow in an
      obstructed urethra, we describe the main non-invasive techniques: penile urethral
      compression-release (PCR), cuffs, and condoms. Using the VBN method, we tried to
      quantify data from these techniques to specify the relation with the usual
      parameters of bladder outlet obstruction. RESULTS: In the absence of brisk change
      of the flow rate, the voiding phases are easily analyzed. With minor corrections,
      recorded external or cuff pressures could be used in the ICS nomogram;
      unfortunately, these pressures are greatly modified by perturbations of the
      nervous control. The spike of flow (due to urine storage in the urethra) observed
      at resumption of flow after each interruption presents mathematical difficulties
      for quantitative and reliable modeling but could give a consistent empirical
      interpretation. CONCLUSION: Of the reported non-invasive tests, all except PCR
      have an important instrumental heaviness and induce strong perturbations of the
      nervous control. If they cannot allow an accurate quantification of urethral
      obstruction and detrusor contractility, they could allow for classification of
      benign prostatic hypertrophy (BPH) patients. Despite the mathematical problems
      set by the theory of spikes, the empirical use of the spikes amplitude could
      perhaps be clinically useful.

PMID- 16616393
TI  - Osteoarthritis: pathobiology-targets and ways for therapeutic intervention.
AB  - Osteoarthritis is first and foremost the ongoing destruction of the articular
      cartilages of joints. Therefore, the extracellular matrix and the cells of the
      articular cartilages are the primary targets of osteoarthritis therapy. This
      tries to inhibit enzymatic destruction of the extracellular cartilage matrix as
      well as the modification of the cellular phenotype of the chondrocytes: cell
      degeneration and cell death are alongside anabolic activation and stabilization
      of the cellular phenotype of major interest. However, apart from the cartilage
      and its cells, other tissues of the joints are also important for the symptoms of
      the disease, which basically all originate outside the articular cartilage. In
      addition, changes in the subchondral bone as well as the synovial capsule and
      membrane are important at least for the progression of the disease process. All
      the named tissues offer different directions and ways for therapeutic
      intervention.

PMID- 16616394
TI  - Estimated impact of LDCT-identified stage IA non-small-cell lung cancer on
      screening efficacy.
AB  - About one-third of individuals radiographically diagnosed with surgical
      pathological stage IA non-small-cell lung cancer (IA-NSCLC) harbor occult
      metastases that prove lethal. A comparison of the projected outcome of CT
      diagnosed IA-NSCLC with actuarial figures for life expectancy of screenees
      suggests that about half of the remainder will succumb to alternative causes. CT
      screening can be efficacious if and only if it leads to an interdiction of
      potentially lethal cancers in the remaining one-third of sufficient magnitude
      that it offsets the surgical mortality and abbreviation of life expectancy in the
      two-thirds who are either understaged or overdiagnosed. Preliminary evidence from
      CT screening trials fails to support the premise that it diminishes the absolute
      number of advanced lung cancers.

PMID- 16616395
TI  - Synthesis and antimicrobial studies of a new series of 2-[4-[2-(5-ethylpyridin-2
      yl)ethoxy]phenyl]-5-substituted-1,3,4-oxadiazoles.
AB  - A series of novel 2-[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]-5-substituted-1,3,4
      oxadiazoles were synthesized by the oxidative cyclisation of hydrazones derived
      from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde and aroylhydrazines using
      chloramine-T as oxidant. IR, NMR and elemental analysis characterized the newly
      synthesized compounds. The synthesized compounds were evaluated for their
      antimicrobial activity and were compared with standard drugs. The compounds
      demonstrated potent to weak antimicrobial activity. Out of the compounds studied,
      compounds 8c and 8d showed significant inhibition. Compounds 8b, 8f, 8k and 8e
      showed moderate activity. The minimum inhibitory concentration of the compounds
      was in the range of 8-26 microg ml(-1) against bacteria and 8-24 microg ml(-1)
      against fungi. The title compounds represent a novel class of potent
      antimicrobial agents.

PMID- 16616396
TI  - Synthesis and studies on some new fluorine containing triazolothiadiazines as
      possible antibacterial, antifungal and anticancer agents.
AB  - Synthesis of a series of 7-arylidene-6-(2,4-dichlorophenyl)-3
      aryloxymethyl/anilinomethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) by the
      condensation of 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-propen-1-one (1)
      and 4-amino-5-mercapto-3-aryloxymethyl/anilinomethyl-1,2,4-triazoles (2) is
      described. The newly synthesized compounds were characterized by elemental
      analysis IR, 1H NMR and mass spectral data. These compounds were tested for their
      antimicrobial activities against Escherichia coli, Staphylococcus aureus (Smith),
      Psuedomonas aeruginosa (Gessard), Bacillus subtilis and Candida albicans. Some of
      the newly synthesized compounds were also screened for their anticancer activity.
      Among them compounds 3m, 3o, 3q showed in vitro anticancer activity.

PMID- 16616397
TI  - The National Health Service Knowledge and Skills Framework and its implications
      for continuing professional development in nursing.
AB  - The National Health Service Knowledge and Skills Framework has been introduced as
      part of the Agenda for Change Reforms in the United Kingdom to link pay and
      career progression to competency. The purpose of this paper is to consider the
      implications for nurses, their managers and the impact on university departments
      delivering continuing professional development for nurses. The new system has the
      potential to increase the human resources management aspect of the clinical nurse
      managers' role and could have legal implications, for example if practitioners
      perceive that their needs for continuing professional development have been
      overlooked to the detriment of their pay and career aspirations. The new system
      also has implications for providers of continuing professional development in the
      universities and is likely to demand closer liaison between education providers
      and trust staff who commission education and training. The Knowledge and Skills
      Framework is of interest to nurses and nurse educators internationally because
      the system, if effective, could be introduced elsewhere.

PMID- 16616398
TI  - The importance of reciprocity in relationships between community-based midwives
      and mothers.
AB  - OBJECTIVE: to explore the emotion work experiences of community-based midwives,
      focusing on their relationships with clients. DESIGN: a qualitative study using
      an ethnographic approach. Data were collected via observation, interview and
      focus groups. SETTING: a National Health Service (NHS) Trust in South Wales, UK.
      PARTICIPANTS: a purposive sample of 19 NHS community-based midwives, working in
      different teams and with differing lengths of clinical experience. FINDINGS:
      relationships between midwives and women varied considerably, and could be the
      source of emotion work for midwives. A model of midwife-woman relationships is
      proposed, based on the concept of reciprocity. Four key situations are
      identified: balanced exchanges, rejected exchanges, reversed exchanges and
      unsustainable exchanges. Balanced exchanges occur when there is 'give and take'
      on both sides; these are emotionally rewarding for the midwife. The other
      exchanges are out of balance, and require emotion work by the midwife. KEY
      CONCLUSIONS: the concept of reciprocity is a useful analytical tool that enhances
      understanding of midwife-woman relationships and the emotion work that these may
      generate. Increased understanding of these issues is important, given the current
      national and international policy recommendations for health-care professionals
      to work in partnership with clients. IMPLICATIONS FOR PRACTICE: the midwife-woman
      relationship and the factors that affect it need to be explicitly addressed
      within educational settings, in order to further develop interpersonal and
      communication skills. In turn, this should enhance the emotional well-being of
      midwives and the quality of care that women receive. Additional research is
      needed to further develop and refine the model.

PMID- 16616399
TI  - Synovial chrondromatosis of the distal radioulnar joint.

PMID- 16616400
TI  - Distribution and temporal changes of lead in the surface seawater in the western
      Pacific and adjacent seas derived from coral skeletons.
AB  - We determined Pb contents together with Pb isotopic compositions in coral
      skeletons (Porites spp.) collected from the western Pacific and adjacent seas to
      examine distribution of Pb in sea surfaces. Temporal records of Pb were also
      investigated using coral skeletons from Hainan and Ogasawara Island, located in
      China and Japan, respectively. The spatial distribution of Pb showed a clear
      dilution pattern of Pb from Asian continent to the open ocean. Also the similar
      trend was found in the Java Sea from Jakarta to the offshore. In addition to the
      spatial distribution, Pb contents in Ogasawara coral have gradually increased
      during last 108 years. It may be attributed to Pb emission mainly from industrial
      activities in Asian countries. Hainan coral, which provided 10 years record of
      Pb, showed a remarkable decline around 1997 probably due to the partial
      introduction of unleaded gasoline in China.

PMID- 16616401
TI  - Levels of trace elements in green turtle eggs collected from Hong Kong: Evidence
      of risks due to selenium and nickel.
AB  - Concentrations of 22 trace elements were determined in green turtle (Chelonia
      mydas) eggs collected from Hong Kong. Concentrations of selenium, lead and nickel
      in these eggs were generally higher than those reported in other studies. The
      predicted no effect concentrations (PNEC; ng/g wet weight) of Pb (1000), Se (340
      and 6000 for the worst-case and best-case scenarios, respectively) and Ni (17) in
      the green turtle eggs were estimated. Hazard quotients (HQs) estimate that Se
      (HQs: 0.2-24.5) and Ni (HQs: 4.0-26.4) may pose some risks to the turtles. Our
      study also found that concentrations of Ag, Se, Zn, Hg and Pb in the shell of the
      turtle eggs were significantly correlated with levels in the whole egg contents
      (yolk+albumen). Once the precise relationships of specific elements are
      established, egg-shell concentrations may be used as a non-lethal, non-invasive,
      surrogate for predicting whole egg burden of certain contaminants in marine
      turtles.

PMID- 16616402
TI  - Distribution of total mercury, methyl mercury and selenium in pod of killer
      whales (Orcinus Orca) stranded in the northern area of Japan: comparison of
      mature females with calves.
AB  - Total mercury (T-Hg) and selenium (Se) concentrations in liver, kidney and muscle
      from a pod of killer whales including five mature females and three calves
      stranded in the northern area of Japan were analyzed. In the mature female,
      contamination level of T-Hg in the liver sample (62.2+/-21.9 microg/wet g) was
      markedly higher than that in kidney sample and muscle sample. The molar ratio of
      T-Hg to Se in the liver sample was approximately 1, and those in the kidney and
      muscle samples were markedly lower than 1. These results suggest that the
      formation of HgSe compound increases the hepatic accumulation of mercury (Hg). In
      contrast, contamination level of T-Hg in the calf organs was much lower than that
      in the mature female organs. These results suggest that the transfer of Hg from
      the mother to the fetus via placenta and/or to calf via milk is trace.

PMID- 16616403
TI  - Global pilot study for persistent organic pollutants (POPs) using PUF disk
      passive air samplers.
AB  - Polyurethane foam (PUF) disks were deployed at global background sites, to test
      logistical issues associated with a global monitoring network for persistent
      organic pollutants (POPs). alpha-HCH, exhibited relatively high and uniform
      concentrations (17-150 pg/m3) at temperate and arctic sites with elevated
      concentrations associated with trans-Pacific inflow. Concentrations were much
      lower (<5 pg/m3) in Bermuda, Chile and Cape Grim. Concentrations for gamma-HCH,
      the main component of lindane, were spatially similar to the alpha-HCH pattern
      but lower in magnitude (typically, <10 pg/m3). Chlordane concentrations (sum of
      cis-chlordane, trans-chlordane and trans-nonachlor) were also low (<10 pg/m3).
      Dieldrin concentrations were in the range 2-25 pg/m3 at most sites but elevated
      in Bermuda. Back trajectories suggest that advection from Africa and the US may
      contribute. Endosulfan, a popular current-use pesticide, exhibited highest
      concentrations ranging from tens to hundreds of pg/m3. There was good agreement
      between duplicate samplers at each site and PUF disk-derived air concentrations
      agreed with high volume data. Few logistical/analytical problems were encountered
      in this pilot study.

PMID- 16616404
TI  - Mechanisms of competitive adsorption of Pb, Cu, and Cd on peat.
AB  - Combined use of batch equilibration adsorption and X-ray absorption spectroscopy
      (XAS) was employed to study the mechanisms of competitive adsorption of Pb, Cu,
      and Cd on Danish and Heilongjiang peat in single- and multi-solute systems. The
      adsorption capacity and initial adsorption rate on the same peat in single-solute
      systems followed the order Pb>Cu>Cd. Both the adsorbed amount of each metal (q'm)
      and its initial adsorption rate were decreased in multi-solute systems. It was
      observed that the adsorbed amounts of metals at low-energy adsorption sites
      (qm,1) decreased pronouncedly compared to those at high-energy adsorption sites
      (qm,2), indicating that the competitive adsorption of Pb, Cu and Cd occurred
      mainly at the low-energy adsorption sites. XAS study revealed that both Pb and Cu
      were coordinated in peat predominantly to carboxylic moieties without excluding
      the hydroxyl groups, thereby providing an insight into the mechanism of
      competitive adsorption of Pb and Cu on peat.

PMID- 16616405
TI  - The expressions of protooncogenes and CYP1A in lungs of rats exposed to sulfur
      dioxide and benzo(a)pyrene.
AB  - Sulfur dioxide (SO2) is a ubiquitous air pollutant, present in low concentrations
      in the urban air, and in higher concentrations in the working environment.
      Benzo(a)pyrene (B(a)P), a polycyclic aromatic hydrocarbon, is a ubiquitous
      environmental contaminant with diverse toxicological effects. To investigate the
      interactions between SO2 and B(a)P, male Wistar rats were exposed to
      intratracheally instilled with benzo(a)pyrene (B(a)P; 3 mg) or SO2 (20 ppm)
      inhalation alone or together. The mRNA of CYP1A1 and 1A2, c-fos, and c-jun and
      protein levels of c-fos and c-jun were analyzed in lungs using a real-time
      reverse transcription-polymerase chain reaction (real-time RT-PCR) assay and
      Western blot analysis, respectively. And 7-ethoxyresorufin O-deethylase (EROD)
      and methoxyresorufin O-demethylase (MROD) activities were detected. In lungs of
      rats exposed to SO2 alone, the gene transcription of CYP1A1 and 1A2, the EROD and
      MROD activities were decreased. Meanwhile, the mRNA and protein levels of c-jun
      and c-fos were increased significantly. Exposure to B(a)P alone induced CYP1A1,
      CYP1A2 mRNA levels, the protein levels of c-jun, and the EROD and MROD activities
      in lungs. However, exposure to B(a)P plus inhaled SO2 neither increased nor
      decreased CYP1A1/2 mRNA expressions, EROD, and MROD activities in lungs, versus
      exposure to B(a)P alone. Nevertheless, exposure to B(a)P plus inhaled SO2
      increased the mRNA and protein levels of c-jun and c-fos in lungs compared with
      lungs exposed to SO2 alone. Accordingly, the SO2-induced decreases of CYP1A1/2
      might not influence the metabolic activation of B(a)P. However, when B(a)P and
      SO2 were given in the combinations, one might postulate that a synergistic effect
      on the expressions of c-fos and c-jun between SO2 and B(a)P, which might be one
      of the possible mechanisms of combination effects between B(a)P and the air
      pollutants.

PMID- 16616406
TI  - Predictors of improvement in social support: Five-year effects of a structured
      intervention for caregivers of spouses with Alzheimer's disease.
AB  - Those who provide care at home for a spouse with Alzheimer's disease (AD) endure
      considerable challenges, including social isolation and increasing caregiving
      responsibilities. We examine the extent to which an intervention that helps
      spouse-caregivers mobilize their social support network, helps them better adapt
      to the caregiving role. We used detailed social support information collected
      from 200 spouse-caregivers participating in a randomized, controlled trial of
      enhanced social support services in the USA. Using random effects regression
      models, we found that individuals in the intervention group reported higher
      levels of satisfaction with their social support network over the first 5 years
      of the intervention than those in the support group. Higher levels of emotional
      support, more visits, and having more network members to whom they felt close
      were all individually predictive of longitudinal changes in social support
      network satisfaction. We conclude with a discussion of the importance of having
      psychological respite when caregivers spend their days in the home and are
      isolated.

PMID- 16616407
TI  - Characterization and expression of a cDNA encoding a tubuliform silk protein of
      the golden web spider Nephila antipodiana.
AB  - Spider silks are renowned for their excellent mechanical properties. Although
      several spider fibroin genes, mainly from dragline and capture silks, have been
      identified, there are still many members in the spider fibroin gene family remain
      uncharacterized. In this study, a novel silk cDNA clone from the golden web
      spider Nephila antipodiana was isolated. It is serine rich and contains two
      almost identical fragments with one varied gap region and one conserved spider
      fibroin-like C-terminal domain. Both in situ hybridization and immunoblot
      analyses have shown that it is specifically expressed in the tubuliform gland.
      Thus, it likely encodes the silk fibroin from the tubuliform gland, which
      supplies the main component of the inner egg case. Unlike other silk proteins,
      the protein encoded by the novel cDNA in water solution exhibits the
      characteristic of an alpha-helical protein, which implies the distinct property
      of the egg case silk, though the fiber of tubuliform silk is mainly composed of
      beta-sheet structure. Its sequence information facilitates elucidation of the
      evolutionary history of the araneoid fibroin genes.

PMID- 16616408
TI  - Laparoscopic hysterectomy versus total abdominal hysterectomy: a comparative
      study.
AB  - OBJECTIVE: The objective of this study was to compare the intraoperative and
      short-term postoperative complications of laparoscopic hysterectomy and total
      abdominal hysterectomy. STUDY DESIGN: Retrospective study of 167 women who had
      laparoscopic hysterectomy and 119 women who had total abdominal hysterectomy. For
      assessing the learning curve, the laparoscopic hysterectomies were further
      subdivided to the first 30 hysterectomies and the later hysterectomies. For data
      analysis Student's t-test, chi2-test and Fisher's exact test were used. RESULTS:
      There were no statistically significant differences between the two groups for
      age, body mass index, previous abdominal surgery, uterine weight, first
      postoperative day hemoglobin drop, blood transfusion and major or minor
      complications rate. Operation time was significantly longer for laparoscopic than
      abdominal hysterectomy (156+/-40 and 91.2+/-33 min, respectively; P<0.001) but
      the length of hospital stay was significantly shorter (3.9 and 6.55 days,
      respectively; P<0.001). The conversion rate of laparoscopic hysterectomy was 1.8%
      (three cases). CONCLUSIONS: Laparoscopic hysterectomy can be safely done even
      during the learning curve with a low and reasonable complication rate, and a
      shorter hospital stay but with longer operation time. As experience is gained the
      operation time, complication rate and hospital stay are decreased.

PMID- 16616409
TI  - Optimization of "Serpa" cheese whey nanofiltration for effluent minimization and
      by-products recovery.
AB  - Second cheese whey (SCW) is a by-product of cheese and curd cheese production
      that is usually not recovered and therefore substantially contributes to the
      negative environmental impact of the cheese manufacture plants. Membrane
      technology, namely nanofiltration (NF), is used in this work for the recovery of
      SCW organic nutrients, resulting from "Serpa" cheese and curd production. The SCW
      is processed by NF to recover a rich lactose fraction in the concentrate and a
      process water with a high salt content in the permeate. The permeation
      experiments were carried out in a plate & frame NF unit, where two NF membranes
      (NFT50 and HR-95-PP) were characterized and tested. The NF permeation experiments
      were performed accordingly with two different operation modes: total
      recirculation and concentration. In order to select the best membrane and
      operating pressure for the SCW fractionation, total recirculation experiments
      were carried out. The NF modeling was also performed, in terms of permeate fluxes
      and rejection coefficients using the resistances-in-series model and the solution
      diffusion model, respectively. After the membrane selection, the concentration
      experiments showed that the selected membrane (NFT50) at 3.0MPa allows a water
      recovery of approximately 80%, concentrating the SCW nutrients approximately 5
      times. Therefore, the NF operation can successfully reduce the wastewater organic
      load and simultaneously contributes to the valorization of the cheese and curd
      cheese manufacture by-products.

PMID- 16616410
TI  - Incomplete mixing in a small, urban stream.
AB  - Conservative solute tracer experiments were conducted in Indian Creek, a small
      urban stream located in Philadelphia, Pennsylvania, USA. Estimated flow rates
      were between 46 Ls(-1) and 81 Ls(-1), average stream width was 5.5m and average
      stream depth was 0.2m. Given these dimensions, most researchers would think it
      reasonable to assume that the stream is completely mixed vertically and
      horizontally. However, we found that the stream was not vertically completely
      mixed in a 1.0m deep, 30 m long pool. The limited mixing was demonstrated by the
      vertical stratification of a tracer cloud which was completely mixed both
      laterally and vertically across the stream prior to entering the pool. We suggest
      that the cause of limited mixing is due to a balance between groundwater inflow
      and transverse dispersion at the cross-section. We show that the unsupported
      assumption of complete mixing may result in a wide range, and thus increased
      uncertainty, of the values of stream flow and longitudinal dispersion coefficient
      estimated from these data. We conclude that the assumption of complete mixing and
      one-dimensional modeling must be checked against actual field conditions, even in
      small streams.

PMID- 16616411
TI  - Optimization of the electrocoagulation process for the removal of copper, lead
      and cadmium in natural waters and simulated wastewater.
AB  - Chemical, electrochemical and flow variables were optimized to examine the
      effectiveness of the electrocoagulation process for the removal of copper, lead
      and cadmium. The electrochemical process, which uses electrodes of commercial
      laminate steel, was applied to simulated wastewater containing 12 mg dm(-3) of
      copper, 4 mg dm(-3) of lead and 4 mg dm(-3) of cadmium. The optimum conditions
      for the process were identified as pH=7, flow rate=6.3 cm(3) min(-1) and a
      current density between 31 and 54 A m(-2). When the electrode geometric area and
      time of electrolysis reached critical values, the copper removal reached a
      maximum value of 80%. A linear relationship was identified between the current
      density and the mass of generated sludge. In addition, a linear relationship was
      found between specific energy consumption and current density. The results of
      this investigation provide important data for the development of an industrial
      scale electrolytic reactor.

PMID- 16616412
TI  - Cost-benefit analyses of radon mitigation projects.
AB  - Radon is a radioactive gas that enters buildings and is known to cause lung
      cancer. Danish building regulation recommends simple remedial measures for radon
      levels between 200 and 400 Bqm(-3), and more effective methods for levels above
      400 Bqm(-3). The Danish National Board of Health found that radon levels in 4.6%
      of the dwellings were above the reference level, and that the distribution of
      radon levels in Danish one-family houses is lognormal with a geometric mean of
      57.7 Bqm(-3) and a geometric standard deviation of 2.28. The purpose of the paper
      is to present a cost-benefit analysis of a possible future governmental
      intervention against radon in existing Danish one-family houses. In other words,
      it seeks to answer the question: is it socio-economically worthwhile to avert
      lung cancer deaths by reducing radon levels in the most exposed dwellings? The
      results indicate that an intervention based on the anti-radon measures
      recommended by the Danish building regulation would, if implemented, avert less
      than 30 deaths each year. By comparison, a total of 300 people die from radon
      exposure annually in Denmark. The total costs exceed the valuated health benefits
      by euro 62 million (6% discount rate). It is concluded that it is not socio
      economically favourable to reduce radon levels in existing Danish one-family
      houses. These results are based on a discount rate of 6%, a value of preventing a
      statistical fatality of euro 1.4 million, and a relatively high cost of
      remediation in Denmark compared to other countries. Based on the sensitivity
      analysis, the conclusion will be different if a discount rate of 4.3% or less is
      used, or if the value of preventing a statistical fatality is euro 2.54 million
      or higher, or if the cost of remediation is reduced.

PMID- 16616413
TI  - Involvement of p44/p42 MAP kinase in insulin-like growth factor-I-induced
      alkaline phosphatase activity in osteoblast-like-MC3T3-E1 cells.
AB  - It has been shown that insulin-like growth factor-I (IGF-I) stimulates the
      activity of alkaline phosphatase, a marker of mature osteoblast phenotype, in
      osteoblasts. In the present study, we investigated the involvement of the mitogen
      activated protein (MAP) kinase superfamily in the IGF-I-stimulated alkaline
      phosphatase activity in osteoblast-like MC3T3-E1 cells. IGF-I-stimulated alkaline
      phosphatase activity dose dependently in the range between 1 nM and 0.1 microM.
      IGF-I induced the phosphorylation of p44/p42 MAP kinase and p38 MAP kinase but
      not stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). PD98059
      and U0126, specific inhibitors of the upstream kinase that activates p44/p42 MAP
      kinase, significantly suppressed the IGF-I-induced alkaline phosphatase activity.
      On the contrary, SB203580 and PD169316, specific inhibitors of p38 MAP kinase,
      failed to affect the activity induced by IGF-I. Specific inhibitors for
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway (LY294002 and wortmannin) also
      had no significant effect on IGF-I-induced p44/p42 MAP kinase phosphorylation.
      The phosphorylation of p44/p42 MAP kinase induced by IGF-I was reduced by U0126.
      These results strongly suggest that p44/p42 MAP kinase among the MAP kinase
      superfamily plays a role in the IGF-I-stimulated alkaline phosphatase activity in
      osteoblast-like MC3T3-E1 cells.

PMID- 16616414
TI  - Combined advanced oxidation and biological treatment processes for the removal of
      pesticides from aqueous solutions.
AB  - Advanced oxidation processes were combined with biological treatment processes in
      this study to remove both pesticides and then the COD load from aqueous
      solutions. It was found that O(3) and O(3)/UV oxidation systems were able to
      reach 90 and 100%, removal of the pesticide Deltamethrin, respectively, in a
      period of 210 min. The use of O(3) combined with UV radiation enhances pesticides
      degradation and the residual pesticide reaches zero in the case of Deltamethrin.
      The combined O(3)/UV system can reduce COD up to 20% if the pH of the solution is
      above 4. Both pesticide degradation and COD removal in the combined O(3)/UV
      system follow the pseudo-first-order kinetics and the parameters of this model
      were evaluated. The application of the biological treatment to remove the bulk
      COD from different types of feed solution was investigated. More than 95% COD
      removal was achieved when treated wastewater by the O(3)/UV system was fed to the
      bioreactor. The parameters of the proposed Grau model were estimated.

PMID- 16616415
TI  - Ambient air particulate concentrations and metallic elements principal component
      analysis at Taichung Harbor (TH) and WuChi Traffic (WT) near Taiwan Strait during
      2004-2005.
AB  - The purpose of this study is to characterize metallic elements associated with
      atmospheric particulate matter of total suspended particulate (TSP), fine
      particle (particle matter with aerodynamical diameter <2.5 microm, PM(2.5)),
      coarse particle (particle matter with aerodynamical diameter 2.5-10 microm, PM
      (2.5-10)) at the Taichung Harbor (TH) and WuChi Traffic (WT) sampling site of
      central Taiwan during March 2004 to February 2005. The result indicated the
      average total suspended particulate concentration in 1 year was 157.31 and 112.58
      microg m(-3) at TH and WT sampling site, respectively. Fine particle (PM(2.5))
      size was the dominant species at TH and WT sampling site. In TH sampling site,
      higher correlation coefficient was observed on total suspended particulates of
      metallic elements Fe and Zn. And in WT sampling site, higher correlation
      coefficients displayed on total suspended particulates of metallic elements Fe
      and Zn, Fe and Mn. Ambient airborne particle principal component analysis of
      metallic metals was used to identify the possible pollutant sources in this
      study. At the TH sampling site, 50.81% of the total variance of the data was
      observed in factor 1. Higher loading of Fe (0.86), Zn (0.79), Pb (0.76), and Mn
      (0.68) were contributed by traffic emission and the soil source. At the WT
      sampling site, factor 1 explained 53.74% of the total variance of the data and
      had high loading for Zn (0.86) and Cu (0.85), which were identified as
      industrial/traffic emission sources.

PMID- 16616416
TI  - Role of the paratrigeminal nucleus in nocifensive responses of rats to chemical,
      thermal and mechanical stimuli applied to the hind paw.
AB  - Anatomical and immunohystochemical data suggest the paratrigeminal nucleus (Pa5)
      may play a role in nociceptive processing. The current study examines the
      influence of unilateral Pa5 lesion on nocifensive responses of conscious rats to
      noxious thermal (Hargreaves test), mechanical (electronic von Frey and Randall
      Selitto tests), and chemical (formalin 2.5%; 50 microl) stimuli applied to the
      hind paw. Lesion of the Pa5 induced by ibotenic acid did not affect the latency
      for radiant heat-induced withdrawal of either paw. In contrast, the mean
      mechanical threshold for withdrawal of the contralateral (but not ipsilateral)
      paw in Pa5-lesioned rats was reduced by approximately 45% and 20%, in electronic
      von Frey and Randall-Selitto tests, respectively, when compared to sham-operated
      animals. Conversely, animals with Pa5 lesions injected with formalin in the
      contralateral paw spent less time engaged in focused (licking, biting or
      scratching the injected paw) and total nocifensive behavior (i.e., focused
      nocifensive behavior plus protection of the injected paw during movements) in
      both the first and second phases of the test [ approximately 50% inhibition of
      each parameter during first phase (0-5 min) and at 20, 25, and 30 min of second
      phase, relative to the sham-operated group], but the number of paw-jerks was
      unaffected. Pa5 lesion also delayed the onset of second phase focused pain
      induced by formalin in the ipsilateral paw. The results suggest that the Pa5
      integrates the supraspinal pain control system and plays a differential
      modulatory role in the central processing of mechanical and chemical nociceptive
      information.

PMID- 16616417
TI  - The role of ERK signaling and the P2X receptor on mechanical pain evoked by
      movement of inflamed knee joint.
AB  - Pain during inflammatory joint diseases is enhanced by the generation of
      hypersensitivity in nociceptive neurons in the peripheral nervous system. To
      explore the signaling mechanisms of mechanical hypersensitivity during joint
      inflammation, experimental arthritis was induced by injection of complete
      Freund's adjuvant (CFA) into the synovial cavity of rat knee joints. As a pain
      index, the struggle threshold of the knee extension angle was measured. In rats
      with arthritis, the phosphorylation of extracellular signal-regulated kinase
      (ERK), induced by passive joint movement, increased significantly in dorsal root
      ganglion (DRG) neurons innervating the knee joint compared to the naive rats that
      received the same movement. The intrathecal injection of a MEK inhibitor, U0126,
      reduced the phosphorylation of ERK in DRG neurons and alleviated the struggle
      behavior elicited by the passive movement of the joint. In addition, the
      injection of U0126 into the joint also reduced the struggle behavior. These
      findings indicate that the ERK signaling is activated in both cell bodies in DRG
      neurons and peripheral nerve fibers and may be involved in the mechanical
      sensitivity of the inflamed joint. Furthermore, the phosphorylated ERK-positive
      neurons co-expressed the P2X3 receptor, and the injection of TNP-ATP, which
      antagonizes P2X receptors, into the inflamed joint reduced the phosphorylated ERK
      and the struggle behavior. Thus, it is suggested that the activation of the P2X3
      receptor is involved in the phosphorylation of ERK in DRG neurons and the
      mechanical hypersensitivity of the inflamed knee joint.

PMID- 16616418
TI  - Determining anatomical connectivities between cortical and brainstem pain
      processing regions in humans: a diffusion tensor imaging study in healthy
      controls.
AB  - Neuroimaging methods have so far identified various structures in the brain
      involved in the processing of pain and its control. However, our understanding of
      their anatomical connectivities is relatively weak. Diffusion tensor imaging
      (DTI), a magnetic resonance imaging-based method, allows in vivo mapping of the
      anatomical connections in the human brain and was used to investigate the white
      matter connections originating from the periaquaductal grey (PAG) and nucleus
      cuneiformis (NCF). We performed DTI on 8 healthy right-handed male volunteers.
      Group analysis showed that tract paths could be defined and their likelihood
      quantified for connections between the PAG and separately for the NCF, to the
      prefrontal cortex, amygdala, thalamus, hypothalamus and rostroventral medial
      medulla bilaterally. The connections identified confirm the existence of an
      anatomical circuitry for the functionally characterised top-down influences on
      pain processing via brainstem structures in humans.

PMID- 16616419
TI  - Changes to somatosensory detection and pain thresholds following high frequency
      repetitive TMS of the motor cortex in individuals suffering from chronic pain.
AB  - Research has shown that transcranial magnetic stimulation (TMS) results in a
      transient reduction in the experience of chronic pain. The present research aimed
      to investigate whether a single session of high frequency TMS is able to change
      the sensory thresholds of individuals suffering from chronic pain. Detection and
      pain thresholds for cold and heat sensations were measured before and after 20Hz
      repetitive TMS (rTMS) administered over the motor cortex. A significant decrease
      in temperature for cold detection and pain thresholds and a significant increase
      in temperature for heat pain thresholds were evident following a single session
      of rTMS. In contrast, no change in detection and pain thresholds was obtained
      following sham rTMS. The finding that rTMS can have a direct effect on sensory
      thresholds in individuals suffering from chronic pain has implications for the
      therapeutic use of rTMS in the relief of chronic pain.

PMID- 16616420
TI  - Burning questions about the brain in pain.

PMID- 16616421
TI  - Motor cortex stimulation for central pain following a traumatic brain injury.
AB  - Central pain can occur in any lesions along the central nervous system affecting
      the spinothalamocortical pathway. Although diverse etiologies have been reported
      to cause central pain, there are few reports on the occurrence and surgical
      treatment of central pain following a traumatic brain injury (TBI). This paper
      describes the occurrence of central pain following a severe TBI, in which the
      diagnosis of central pain was typically delayed due to the patient's decreased
      ability to express his pain for severe aphasia as a neurological sequela. The
      severe burning pain, deep pressure-like pain, and deep mechanical allodynia,
      which presented over the contralateral side to the TBI, were successfully
      relieved with motor cortex stimulation (MCS). The analgesic effect of stimulation
      was found to be long lasting and was still present at the 12-month follow up. As
      shown in this patient, the occurrence of central pain syndrome should be
      considered by physicians caring for TBI patients, and a comprehensive, systematic
      study will be needed to determine the prevalence of central pain after a TBI.

PMID- 16616422
TI  - CTF determination and correction in electron cryotomography.
AB  - Electron cryotomography (cryoET) has the potential to elucidate the structure of
      complex biological specimens at molecular resolution but technical and
      computational improvements are still needed. This work addresses the
      determination and correction of the contrast transfer function (CTF) of the
      electron microscope in cryoET. Our approach to CTF detection and defocus
      determination depends on strip-based periodogram averaging, extended throughout
      the tilt series to overcome the low contrast conditions found in cryoET. A method
      for CTF correction that deals with the defocus gradient in images of tilted
      specimens is also proposed. These approaches to CTF determination and correction
      have been applied here to several examples of cryoET of pleomorphic specimens and
      of single particles. CTF correction is essential for improving the resolution,
      particularly in those studies that combine cryoET with single particle averaging
      techniques.

PMID- 16616423
TI  - Footpad reaction induced by Neospora caninum tachyzoite extract in infected
      BALB/c mice.
AB  - Little information is available regarding a delayed type hypersensitivity (DTH)
      reaction in neosporosis. In this study, we examined the elicitation of a DTH
      reaction in mice infected with Neospora caninum by inoculation of the footpad
      with tachyzoite antigens. The footpads of BALB/c mice infected with N. caninum
      and those of non-infected were injected with either the tachyzoite extract, or
      paraformaldehyde-fixed tachyzoites. In mice inoculated with N. caninum antigens
      on day 7 p.i. swelling peaked at 6h after injection of the tachyzoite extract. In
      mice inoculated on days 14, 28 and 56, swelling was observed between 6 and 72 h
      afterwards. Mice immunized with the tachyzoite extract plus adjuvant showed peak
      footpad swelling at 6h post injection, and the swelling had decreased at 24h or
      later. In contrast, mice injected before infection showed no specific swelling.
      In sections of footpads injected with the tachyzoite extract, exudate had
      accumulated at 6h post injection and clusters of infiltrated lymphocytes were
      observed at 48 h post injection. In mice administered anti-CD4+ cell monoclonal
      antibodies swelling had decreased at 24h post injection of the extract. These
      results indicate that mice infected with N. caninum produce a DTH reaction, which
      is a good indicator of the development of type 1 immune responses.

PMID- 16616424
TI  - Campest-5-en-3-one, an oxidized derivative of campesterol, activates PPARalpha,
      promotes energy consumption and reduces visceral fat deposition in rats.
AB  - Dietary campest-5-en-3-one (campestenone), an oxidized derivative of campesterol,
      significantly reduced visceral fat weight and the concentration of
      triacylglycerol in serum and liver of rats. Dietary campestenone dramatically
      increased the activities and the mRNA expressions of mitochondrial and
      peroxisomal enzymes involved in beta-oxidation in the liver. Campestenone
      activated human peroxisome proliferator-activated receptor (PPAR) alpha as
      determined using the novel GAL4 ligand-binding domain chimera assay system with
      coactivator coexpression. In contrast, dietary campestenone reduced the
      activities and the mRNA expressions of enzymes involved in fatty acid synthesis,
      except for the malic enzyme. Dietary campestenone decreased the sterol regulatory
      element binding protein-1 (SREBP-1) mRNA level. Energy expenditure was
      significantly higher in the feeding of campestenone in rats. Dietary campestenone
      reduced hepatic cholesterol concentration and increased fecal excretion of
      neutral steroids originated from cholesterol. Lymphatic absorption of cholesterol
      was reduced by the coadministration of campestenone in rats cannulated in the
      thoracic duct. These observations suggest a possibility that campestenone has an
      ability to prevent coronary heart disease by improving obesity and abnormality of
      lipid metabolism.

PMID- 16616425
TI  - C/EBPalpha: a tumour suppressor in multiple tissues?
AB  - The CCATT/enhancer binding protein alpha, C/EBPalpha, is a key transcription
      factor involved in late differentiation events of several cell types. Besides
      acting as a classical transcription factor, C/EBPalpha is also a well
      characterized inhibitor of mitotic growth in most cell lines tested. In line with
      its anti-mitotic properties, C/EBPalpha has been shown to interact with, and
      alter the activities of, several cell cycle related proteins and a number of
      models as to the mechanistics of C/EBPalpha-mediated growth repression have been
      proposed. More recently, several reports have indicated that C/EBPalpha acts as a
      tumour suppressor in the hematopoietic system and that mutation within C/EBPalpha
      is sufficient to induce tumourigenesis. Here, we will review these data and probe
      the possibility that C/EBPalpha also act as a tumour suppressor in other
      C/EBPalpha-expressing tissues.

PMID- 16616427
TI  - Developmental changes in presynaptic muscarinic modulation of excitatory and
      inhibitory neurotransmission in rat piriform cortex in vitro: relevance to
      epileptiform bursting susceptibility.
AB  - Suppression of depolarizing postsynaptic potentials and isolated GABA-A receptor
      mediated fast inhibitory postsynaptic potentials by the muscarinic acetylcholine
      receptor agonist, oxotremorine-M (10 microM), was investigated in adult and
      immature (P14-P30) rat piriform cortical (PC) slices using intracellular
      recording. Depolarizing postsynaptic potentials evoked by layers II-III
      stimulation underwent concentration-dependent inhibition in oxotremorine-M that
      was most likely presynaptic and M2 muscarinic acetylcholine receptor-mediated in
      immature, but M1-mediated in adult (P40-P80) slices; percentage inhibition was
      smaller in immature than in adult piriform cortex. In contrast, compared with
      adults, layer Ia-evoked depolarizing postsynaptic potentials in immature piriform
      cortex slices in oxotremorine-M, showed a prolonged multiphasic depolarization
      with superimposed fast transients and spikes, and an increased 'all-or-nothing'
      character. Isolated N-methyl-d-aspartate receptor-mediated layer Ia depolarizing
      postsynaptic potentials (although significantly larger in immature slices) were
      however, unaffected by oxotremorine-M, but blocked by dl-2-amino-5
      phosphonovaleric acid. Fast inhibitory postsynaptic potentials evoked by layer Ib
      or layers II-III-fiber stimulation in immature slices were significantly smaller
      than in adults, despite similar estimated mean reversal potentials (
      approximately -69 and -70 mV respectively). In oxotremorine-M, only layer Ib-fast
      inhibitory postsynaptic potentials were suppressed; suppression was again most
      likely presynaptic M2-mediated in immature slices, but M1-mediated in adults. The
      degree of fast inhibitory postsynaptic potential suppression was however, greater
      in immature than in adult piriform cortex. Our results demonstrate some important
      physiological and pharmacological differences between excitatory and inhibitory
      synaptic systems in adult and immature piriform cortex that could contribute
      toward the increased susceptibility of this region to muscarinic agonist-induced
      epileptiform activity in immature brain slices.

PMID- 16616426
TI  - Short exposure to an enriched environment accelerates plasticity in the barrel
      cortex of adult rats.
AB  - Cortical sensory neurons adapt their response properties to use and disuse of
      peripheral receptors in their receptive field. Changes in synaptic strength can
      be generated in cortex by simply altering the balance of input activity, so that
      a persistent bias in activity levels modifies cortical receptive field
      properties. Such activity-dependent plasticity in cortical cell responses occurs
      in rat cortex when all but two whiskers are trimmed for a period of time at any
      age. The up-regulation of evoked responses to the intact whiskers is first seen
      within 24 h in the supragranular layers [Laminar comparison of somatosensory
      cortical plasticity. Science 265(5180):1885-1888] and continues until a new
      stable state is achieved [Experience-dependent plasticity in adult rat barrel
      cortex. Proc Natl Acad Sci U S A 90(5):2082-2086; Armstrong-James M, Diamond ME,
      Ebner FF (1994) An innocuous bias in whisker use in adult rat modifies receptive
      fields of barrel cortex neurons. J Neurosci 14:6978-6991]. These and many other
      results suggest that activity-dependent changes in cortical cell responses have
      an accumulation threshold that can be achieved more quickly by increasing the
      spike rate arising from the active region of the receptive field. Here we test
      the hypothesis that the rate of neuronal response change can be accelerated by
      placing the animals in a high activity environment after whisker trimming. Test
      stimuli reveal an highly significant receptive field bias in response to intact
      and trimmed whiskers in layer IV as well as in layers II-III neurons in only 15 h
      after whisker trimming. Layer IV barrel cells fail to show plasticity after 15-24
      h in a standard cage environment, but produce a response bias when activity is
      elevated by the enriched environment. We conclude that elevated activity achieves
      the threshold for response modification more quickly, and this, in turn,
      accelerates the rate of receptive field plasticity.

PMID- 16616428
TI  - A novel neuronal cell line derived from the ventrolateral region of the
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nucleus of the anterior hypothalamus is the center of an
      internal biological clock in mammals. Glutamate is the neurotransmitter of retino
      hypothalamic tract responsible for mediating the circadian actions of light in
      rodents. N-methyl-d-aspartate receptors, particularly NR2B subunit are reported
      to be principally involved in photic resetting of the biological clock in vivo
      and in slice culture. But, the precise cellular mechanisms of the resetting are
      not elucidated, because no adequate neuronal cell lines derived from the
      suprachiasmatic nucleus have been established. We established a neuronal cell
      line, N14.5, derived from the suprachiasmatic nucleus of a transgenic rat
      harboring the temperature-sensitive simian virus 40 large T-antigen gene. When
      the cells were cultured at 39 degrees C, the morphological features were turned
      fibroblastic into neuronal round cell body with neurite extensions. These cells
      showed immunoreactivities for neuronal markers (betaIII-tubulin, microtubule
      associated protein 2 and TAU2) and as well as for vasoactive intestinal peptide
      which is expressed in the ventrolateral region of the suprachiasmatic nucleus.
      The cells expressed N-methyl-d-aspartate receptors, particularly NR1 and NR2B
      subunits as revealed by quantitative PCR. N-methyl-d-aspartate activated
      phosphorylation of p44/42 mitogen-activated protein kinase and increased
      expression level of Per1 and Per2 mRNA. These results suggest that the N14.5 is a
      novel neuronal cell line derived from the ventrolateral region of the
      suprachiasmatic nucleus, and that N-methyl-d-aspartate receptors expressed in the
      cells are a functional receptor. The N14.5 cells may be a useful tool to
      elucidate numerous chronobiological processes, especially resetting mechanism
      induced by an external light signal.

PMID- 16616429
TI  - Repeated brief epileptic seizures by pentylenetetrazole cause neurodegeneration
      and promote neurogenesis in discrete brain regions of freely moving adult rats.
AB  - Recurrent epileptic seizures are known to provoke various forms of cellular
      reorganization in the brains of humans and experimental animals. However, little
      is known about the mechanism of neuronal cell death resulting from epileptic
      seizures elicited by GABA antagonists. In the present study, we explored the
      effect on the central nervous systems of freely moving adult rats, of repeated
      brief epileptic seizures induced by systemic injection of pentylenetetrazole, a
      GABA-A receptor antagonist. Starting with minor convulsions, repeated epileptic
      seizures elicited a progressive increase in seizure severity, culminating in the
      fully kindled state. Histological examination showed that the epileptic seizures
      caused overt neuronal cell death in the limbic system, including the hippocampus
      and amygdala, and its adjoining cortex. During the recurrent epileptic seizures,
      neurogenesis occurred in the subgranular zone of the hippocampus, the
      subventricular zone of the lateral ventricle, and the amygdala. This type of
      pentylenetetrazole-induced neurogenesis was seen at an early stage of
      epileptogenesis in some regions in which massive cell loss was not evident. This
      suggests that neurogenesis is not a secondary consequence of neuronal cell death,
      but rather an independent effect of recurrent epileptic seizures.

PMID- 16616430
TI  - Localization of the Na(+)-coupled neutral amino acid transporter 2 in the
      cerebral cortex.
AB  - We studied the distribution and cellular localization of Na(+)-coupled neutral
      amino acid transporter 2, a member of the system A family of amino acid
      transporters, in the rat and human cerebral cortex using immunocytochemical
      methods. Na(+)-coupled neutral amino acid transporter 2-positive neurons were
      pyramidal and non-pyramidal, and Na(+)-coupled neutral amino acid transporter
      2/GABA double-labeling studies revealed that Na(+)-coupled neutral amino acid
      transporter 2 was highly expressed by GABAergic neurons. Double-labeling studies
      with the synaptophysin indicated that rare axon terminals express Na(+)-coupled
      neutral amino acid transporter 2. Na(+)-coupled neutral amino acid transporter 2
      immunoreactivity was also found in astrocytes, leptomeninges, ependymal cells and
      choroid plexus. Electron microscopy showed robust Na(+)-coupled neutral amino
      acid transporter 2-immunoreactivity in the somato-dendritic compartment of
      neurons and in glial processes, but, as in the case of double-labeling studies,
      failed to reveal Na(+)-coupled neutral amino acid transporter 2-immunoreactivity
      in terminals. To rule out the possibility that the absence of Na(+)-coupled
      neutral amino acid transporter 1- and Na(+)-coupled neutral amino acid
      transporter 2-positive terminals was due to insufficient antigen detection, we
      evaluated Na(+)-coupled neutral amino acid transporter 1/synaptophysin and Na(+)
      coupled neutral amino acid transporter 2/synaptophysin coexpression using non
      standard immunocytochemical procedures and found that Na(+)-coupled neutral amino
      acid transporter 1 and Na(+)-coupled neutral amino acid transporter 2+ terminals
      were rare in all conditions. These findings indicate that Na(+)-coupled neutral
      amino acid transporter 1 and Na(+)-coupled neutral amino acid transporter 2 are
      virtually absent in cortical terminals, and suggest that they do not contribute
      significantly to replenishing the Glu and GABA transmitter pools through the
      glutamate-glutamine cycle. The strong expression of Na(+)-coupled neutral amino
      acid transporter 2 in the somato-dendritic compartment and in non-neuronal
      elements that are integral parts of the blood-brain and brain-cerebrospinal fluid
      barrier suggests that Na(+)-coupled neutral amino acid transporter 2 plays a role
      in regulating the levels of Gln and other amino acids in the metabolic
      compartment of cortical neurons.

PMID- 16616431
TI  - Stable expression of the vesicular GABA transporter following photothrombotic
      infarct in rat brain.
AB  - Before exocytotic release of the inhibitory neurotransmitter GABA, this amino
      acid has to be stored in synaptic vesicles. Accumulation of GABA in vesicles is
      achieved by a specific membrane-integrated transporter termed vesicular GABA
      transporter. This vesicular protein is mainly located at presynaptic terminals of
      GABAergic interneurons. In the present study we investigated the effects of focal
      ischemia on the expression of the vesicular GABA transporter. Vesicular GABA
      transporter mRNA and protein expression was examined after photothrombosis in
      different cortical and hippocampal brain regions of Wistar rats. In situ
      hybridization and quantitative real-time RT-PCR were performed to analyze
      vesicular GABA transporter mRNA. Both vesicular GABA transporter mRNA-stained
      perikarya and mRNA expression levels remained unaffected. Vesicular GABA
      transporter protein-containing synaptic terminals and somata were visualized by
      immunohistochemistry. The pattern of vesicular GABA transporter immunoreactivity
      as well as the protein expression level revealed by semiquantitative image
      analysis and by Western blot remained stable after stroke. The steady expression
      of vesicular GABA transporter mRNA and protein after photothrombosis indicates
      that the exocytotic release mechanism of GABA is not affected by ischemia.

PMID- 16616432
TI  - Facilitation of spike-wave discharge activity by lipopolysaccharides in Wistar
      Albino Glaxo/Rijswijk rats.
AB  - In normal rats the proinflammatory cytokines like interleukin-1beta, interleukin
      6, which are induced by bacterial lipopolysaccharides, are able to control
      thalamo-cortical excitability by exerting strong effects on physiological
      synchronization such as sleep and on pathological synchronization like that in
      epileptic discharges. To investigate whether proinflammatory cytokines or
      lipopolysaccharides could modulate absence seizures resulting from a very
      different generator mechanism than the already investigated bicuculline-,
      kindling- and kainate-induced seizures, we used a genetically epileptic Wistar
      Albino Glaxo/Rijswijk rat strain, which is spontaneously generating high voltage
      spike-wave discharges. Wistar Albino Glaxo/Rijswijk rats responded with an
      increase of the number of spike-wave discharges to lipopolysaccharide injection
      (from 10 microg/kg to 350 microg/kg). Repetitive administration of 350 microg/kg
      lipopolysaccharides daily for 5 days increased the number of spike-wave
      discharges on the first, second and third days but the number of spike-wave
      discharges returned to the control value on day 5, at the 5th injection of
      lipopolysaccharides, showing a tolerance to lipopolysaccharides. The
      lipopolysaccharide-induced increase in spike-wave discharges was not directly
      correlated with the elevation of the core body temperature, as it is in febrile
      seizures, although lipopolysaccharide induced prostaglandin and is clearly
      pyrogenic at the doses used. Indomethacin, the prostaglandin synthesis inhibitor,
      efficiently blocked lipopolysaccharide-induced enhancement of spike-wave
      discharge genesis suggesting that the spike-wave discharge facilitating effect of
      lipopolysaccharides involves induction of cyclooxygenase 2 and subsequent
      synthesis and actions of prostaglandin E2. Low dose (40 mg/kg, i.p.) of
      competitive N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic
      acid, and low dose of lipopolysaccharide (20 microg/kg) showed a synergistic
      interaction to increase the number of spike-wave discharges, whereas at
      supramaximal doses of lipopolysaccharide and the N-methyl-D-aspartate antagonist
      no synergy was present. The data reveal a functional connection between absence
      epileptic activity and lipopolysaccharide induction of prostaglandin synthesis
      and prostaglandin action and suggest some common cellular targets in epilepsy and
      lipopolysaccharide-induced inflammation.

PMID- 16616433
TI  - The role of drug use outcome expectancies in substance abuse risk: an
      interactional-transformational model.
AB  - While a variety of risk factors for substance abuse have been identified, the
      psychological mechanisms underlying the transmission of risk is unclear based on
      studies using traditional risk-outcome research designs. The present paper
      identifies drug use outcome expectancies as a common etiological mechanism
      involved in substance abuse risk. Existing literature findings are reviewed and
      integrated according to an interactional-transformational (IT) model of
      developmental psychopathology. This model identifies the preliminary (mediating)
      and secondary (moderating) role of drug expectancies as important operations
      involved in the development of substance use patterns. Advantages of the IT model
      over traditional trait-based or environmental models are discussed, along with
      implications for intervention and future research.

PMID- 16616434
TI  - Motives for drinking, alcohol consumption, and alcohol-related problems among
      British secondary-school and university students.
AB  - Relationships among reasons for drinking, alcohol consumption, and drinking
      related problems were assessed among secondary-school students (N=328) and
      university students (N=74) in North Wales, United Kingdom, and results were
      compared with results from North America. The ability of drinking reasons to
      predict drinking problems was tested in both age groups. Khavari Alcohol Test,
      Quantity-Frequency-Variability Index, Reasons for Drinking Questionnaire, and
      Rutgers Alcohol Problems Index were used to measure the variables of interest.
      Regression and mediational analyses indicated that negative reasons were stronger
      predictors of drinking problems than were positive reasons among both secondary
      school and university students. Results also showed that the effect of both
      positive and negative drinking reasons on alcohol-related problems was partially
      mediated by alcohol consumption among both secondary-school students and
      university students. There were different correlates of problematic drinking
      among younger and older students, which suggest that different types of
      intervention should be used with the two age groups.

PMID- 16616435
TI  - Hypothalamic pathogenesis of type 2 diabetes.
AB  - There have recently been increasing experimental and clinical evidences
      suggesting that hypothalamic dysregulation may be one of the underlying
      mechanisms of abnormal glucose metabolism. First, increased hypothalamic
      pituitary-adrenal axis activity induced by uncontrollable excess stress may cause
      diabetes mellitus as well as dyslipidemia, visceral obesity, and osteoporosis
      with some resemblance to Cushing's disease. Second, several molecules are known
      to be expressed both in pancreas and hypothalamus; adenosine triphosphate
      sensitive potassium channels, malonyl-CoA, glucokinase, and AMP-activated protein
      kinase. Those molecules appear to form an integrated hypothalamic system, which
      may sense hypothalamic fuel status, especially glucose level, and inhibit action
      of insulin on hepatic gluconeogenesis, thereby forming a brain-liver circuit.
      Third, hypothalamic resistance to insulin as an adiposity signal may be involved
      in pathogenesis of peripheral insulin resistance. The results with mice with a
      neuron-specific disruption of the insulin receptor gene or those lacking insulin
      receptor substrate 2 in hypothalamus supported this possibility. Finally, it has
      very recently been suggested that dysregulation of clock genes in hypothalamus
      may cause abnormal glucose metabolism. Taken together, it is plausible that some
      hypothalamic abnormality may underlie at least some portion of type 2 diabetes or
      insulin resistance in humans, and this viewpoint of hypothalamic pathogenesis of
      type 2 diabetes may lead to the development of new drugs for type 2 diabetes.

PMID- 16616436
TI  - Physics models of centriole replication.
AB  - Our previous pre-clinic experimental results have showed that the
      epithelialization can be enhanced by the externally applied rectangular pulsed
      electrical current stimulation (RPECS). The results are clinically significant
      for patients, especially for those difficult patients whose skin wounds need long
      periods to heal. However, the results also raise questions: How does the RPECS
      accelerate the epithelium cell proliferation? To answer these questions, we have
      previously developed several models for animal cells, in a view of physics, to
      explain mechanisms of mitosis and cytokinesis at a cellular level, and separation
      of nucleotide sequences and the unwinding of a double helix during DNA
      replication at a bio-molecular level. In this paper, we further model the
      mechanism of centriole replication during a natural and normal mitosis and
      cytokinesis to explore the mechanism of epithelialization enhanced with the
      externally applied RPECS at a bio-molecular level. Our models suggest: (1)
      Centriole replication is an information flowing. The direction of the information
      flowing is from centrioles to centrioles based on a cylindrical template of 9 x 3
      protein microtubules (MTs) pattern. (2) A spontaneous and strong electromagnetic
      field (EMF) force is a pushing force that separates a mother and a daughter
      centrioles in centrosomes or in cells, while a pulling force of interacting
      fibers and pericentriolar materials delivers new babies. The newly born babies
      inherit the pattern information from their mother(s) and grow using microtubule
      fragments that come through the centrosome pores. A daughter centriole is always
      born and grows along stronger EMF. The EMF mostly determines centrioles positions
      and plays key role in centriole replication. We also hypothesize that the normal
      centriole replication could not been disturbed in centrosome in the epithelium
      cells by our RPECS, because the centrioles have two non-conducting envelope (cell
      and centrosome membranes), that protect the normal duplication. The induced
      electric field by externally applied RPECS could be mild compared with the
      spontaneous and natural electric field of the centrioles. Therefore, the
      centriole replication during the epithelium cellular proliferation may be
      directly, as well as indirectly (e.g., somatic reflex) accelerated by the RPECS.

PMID- 16616437
TI  - Rationale and methodology for testing auditory cognition in songbirds.
AB  - Songbirds, and in particular zebra finches, present a wonderful opportunity to
      study cognition in species that have evolved specialized abilities and brain
      structures for auditory cognition. The authors describe the rationale, methods,
      and apparatus used to test the auditory perceptual and cognitive abilities of
      songbirds. They have developed an operant conditioning system for conducting
      discrimination experiments simultaneously with several songbirds. The system uses
      specialized single-board computers, standard personal computers, CD-ROMs, and
      custom-written software to present stimuli, control training, and record
      responses. Also, the authors describe software to produce high-quality
      synthesized and naturally occurring acoustic stimuli for use in studies of
      auditory cognition. Typical results from a challenging frequency-range
      discrimination are included.

PMID- 16616438
TI  - A Salmonella-based, propionate-inducible, expression system for Salmonella
      enterica.
AB  - The expression and regulatory properties of a propionate-regulated overexpression
      system (Salmonella enterica prpBCDE promoter (P(prpB)) and positive regulator
      (prpR)) were evaluated in wild-type S. enterica serovar Typhimurium TR6583 and
      prpB(-) or prpD(-) versions of this strain and compared with the arabinose
      regulated T7 expression system. The wild-type strain showed low expression in the
      absence of propionate and high expression in the presence of propionate under all
      growth conditions. In 96-well plates and culture tubes, the wild-type strain
      exhibited a long delay before full induction; the time delay was significantly
      shorter in shake flasks. The prpD(-) strain exhibited low expression in the
      presence of glucose, highly regulatable expression over a wide range of
      propionate concentrations, and, in contrast to the wild-type strain, fast
      induction to full expression under all growth conditions. In contrast, the prpB(
      ) strain showed very high background expression in both culture tubes and shake
      flasks.

PMID- 16616439
TI  - Perinatal management of congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) retains high mortality due to lung
      hypoplasia and pulmonary hypertension. Efforts to improve survival and outcome
      have included fetal intervention, delivery at specialist centres, elective
      operation after stabilisation of labile physiology and minimising barotrauma.
      Permissive hypercapnea ('gentle ventilation') represents a significant advance in
      therapy gaining wider acceptance in centres worldwide. Human genetic studies are
      underway to identify candidate genes for the birth defect. Progress in the basic
      sciences may uncover critical aspects of developmental biology fundamental to
      CDH. Clinical trends in perinatal management of CDH are highlighted, which
      underpin the challenges of this lethal human anomaly.

PMID- 16616440
TI  - Anti-apoptotic effect of hepatocyte growth factor from actinomycin D in
      hepatocyte-derived HL7702 cells is associated with activation of PI3K/Akt
      signaling.
AB  - Actinomycin D (ActD) is a well-known cytotoxic chemotherapeutic reagent and the
      prevention of ActD-induced apoptotic cell death has been an attractive issue for
      biomedical investigators. Since phosphatidylinositol-3 kinase (PI3K)/Akt pathway
      is essential for cell survival, the present study has examined whether the
      preventive effect of hepatocyte growth factor (HGF) on ActD-induced apoptotic
      cell death in a human hepatocyte-derived cell line (HL7702) is associated with
      PI3K/Akt activation. Apoptotic cell death was measured by several methods
      including Hoechst 33342 staining, DNA fragmentation, and flow cytometry. We found
      that ActD caused a significant increase in apoptotic cell death, an effect
      significantly prevented by pre-addition of HGF in the cultures. HGF was found to
      significantly activate Akt phosphorylation while pre-treatment with PI3K specific
      inhibitor wortmannin further enhanced ActD-induced apoptotic effect, and also
      significantly prevented HGF's protection against ActD-induced apoptosis. These
      results suggest that HGF's prevention of ActD-induced apoptotic cell death in
      HL7702 cells is associated with the activation of PI3K/Akt signaling.

PMID- 16616441
TI  - Influence of reproductive stage at PRID insertion on synchronization of estrus
      and ovulation in mares.
AB  - In the present study, we investigated the effects of reproductive status, size of
      follicles and plasma progesterone concentrations of mares at PRID insertion on
      the efficacy of the treatment, estrous cycle patterns, plasma concentrations of
      progesterone and LH. The progesterone-releasing device (PRID) was administered
      intravaginally to 28 Haflinger mares for 11 days at different reproductive
      stages: anestrus (n=6), estrus (n=11) and diestrus (n=11). Plasma concentrations
      of progesterone at insertion (Day 1) of PRID differed among treatment groups
      (anestrus: 0.2-0.6 ng mL(-1), estrus: 0.2-0.5 and diestrus: 1.6-10.8 ng mL(-1);
      P<0.001). Total secretion of progesterone (area under curve (AUC)) during
      treatment period revealed highest values in diestrus (38.2+/-3.1 ng mL(-1)h(-1))
      followed by estrus (25.1+/-2.7) and anestrus (21.0+/-0.4 ng mL(-1)h(-1); P<0.05).
      Progesterone area under curve (AUC) was positively correlated with initial
      progesterone concentrations (R=0.5; P<0.05), but it did not correlate with the
      interval from PRID removal to ovulation. Plasma concentrations of LH during
      treatment period, were significantly lower in anestrous mares (184.6+/-28.6 ng
      mL(-1)h(-1)) when compared to estrous and diestrous mares (349.7+/-53.3 and
      370.5+/-40.3 ng mL(-1)h(-1); P<0.05). Follicular size at PRID insertion had no
      effects on the intervals from PRID removal to subsequent estrus and ovulation.
      Follicle diameters at removal of PRID were significantly correlated with the
      interval from coil removal to estrus (R=-0.55, P<0.05) and ovulation (R=-0.72,
      P<0.0004) in cyclic mares. In anestrus 0 of 6 (0%) mares, in estrus 5 of 11
      (45.5%) and in diestrus 6 of 11 (54.5%) mares ovulated within a defined interval
      of 1 day before to 1 day after mean interval from PRID removal to ovulation. In
      cyclic mares, response to treatment was significantly higher when compared to
      anestrous mares: almost all mares responded with estrus and ovulation independent
      from the stage of the estrous cycle at the start of treatment. However, accuracy
      of synchronization was still unsatisfactory. In cyclic mares, the plasma
      progesterone concentrations at insertion of PRID seem to be more important for
      the efficacy of the treatment than the assignment to estrous cycle stages.

PMID- 16616442
TI  - Study of an alginate/HPMC-based in situ gelling ophthalmic delivery system for
      gatifloxacin.
AB  - The poor bioavailability and therapeutic response exhibited by conventional
      ophthalmic solutions due to rapid pre-corneal elimination of the drug may be
      overcome by the use of in situ gel-forming systems that are instilled as drops
      into the eye and then undergo a sol-gel transition in the cul-de-sac. The present
      work describes the formulation and evaluation of an ophthalmic delivery system of
      an antibacterial agent, gatifloxacin, based on the concept of ion-activated in
      situ gelation. Alginate (Kelton) was used as the gelling agent in combination
      with HPMC (Methocel E50Lv) which acted as a viscosity-enhancing agent. The
      rheological behaviors of all formulations were not affected by the incorporation
      of gatifloxacin. Both in vitro release studies and in vivo pre-corneal retention
      studies indicated that the alginate/HPMC solution retained the drug better than
      the alginate or HPMC E50Lv solutions alone. These results demonstrate that the
      alginate/HPMC mixture can be used as an in situ gelling vehicle to enhance ocular
      bioavailability and patient compliance.

PMID- 16616443
TI  - The application of capillary electrophoresis for enantiomeric separation of N,N
      dimethylamphetamine and its related analogs: intelligence study on N,N
      dimethylamphetamine samples in crystalline and tablet forms.
AB  - This paper reports a new capillary zone electrophoresis method for the
      simultaneous chiral determination of the enantiomers of N,N-dimethylamphetamine
      (DMA), methamphetamine (MA), ephedrine (E), pseudoephedrine (PE) and
      methylephedrine (Me-E). In this study, a number of electophoretic parameters were
      examined and optimized including the choice of chiral selectors, the use of short
      chain tetraalkylammonium cations, the effect of chiral selector concentration,
      buffer concentration, applied voltage and capillary temperature. Heptakis(2,6-di
      O-methyl)-beta-cyclodextrin (DM-beta-CD) and tetrabutylammonium (TBA) being the
      best chiral selector and buffer cation, respectively, the optimized
      electrophoretic conditions were found to be: 20 mM DM-beta-CD, 50 mM TBAPO(4) at
      pH 2.5, applied voltage at 30 kV and temperature at 25 degrees C. Under the
      optimized conditions, all analytes were well separated with resolution factors
      between 3.3 and 24.0 achieved. Using phentermine as an internal standard, the
      intra-day (n=8) precisions for the relative migration times and peak areas of all
      analytes were below 1.09%, while the inter-day precisions (n=12, 6 days) for the
      relative migration times and peak areas of all analytes were under 3.77%. This
      method has been applied to the measurement of the enantiomeric purities of the
      seized DMA samples. The result of the measurement could provide important clues
      about the possible synthetic pathways of these samples.

PMID- 16616444
TI  - Allele frequencies of 15 autosomal STR loci in the Iraq population with
      comparisons to other populations from the middle-eastern region.
AB  - Allele frequencies for the 15 autosomal STR loci included in the AmpFlSTR((R))
      IdentifilerTM PCR Amplification Kit panel from Applied Biosystems (D3S1358, vWA,
      FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, TH01, TPOX, CSF1PO,
      D19S433, D2S1338, D16S539) and several statistical parameters were estimated from
      a sample of 103 unrelated individuals, mostly Shia and Sunni Arabs, living in
      most of central and southern Iraq provinces. We compared the allele frequency
      spectrum detected in the Iraqi population to allele frequencies from 11 other
      data sets from published studies of individuals from Turkey, Iraqi-Kurdistan,
      Saudi Arabia, Arab Emarates, Oman, Iran, Syria, and Jordan. Significant global
      differences in allele frequencies were detected in 9 of the 11 comparisons
      following sequential Bonferroni corrections. Comparisons with the two independent
      panels from Saudi Arabia were not significant after applying Bonferroni
      corrections, however, low P-values (P<0.05) associated with these two contrasts
      nonetheless suggested that at least slight genetic differences between
      populations may exist.

PMID- 16616445
TI  - Radiological findings in autistic and developmentally delayed children.
AB  - PURPOSE: The aim of this study was to evaluate the prevalence of brain
      abnormalities in a group of young children with developmental disorders,
      specifically including children that came to the attention of a child
      psychiatrist before the age of 3 years. METHODS: Forty-five children participated
      in an MR study (mean age 43 months, SD=12, four females). The study design was
      approved by the local Medical Ethical Review Board. All parents gave written
      informed consent. Scans were independently assessed by two board-certified
      radiologists for malformations of gray and white matter. RESULTS: Cohen's kappa
      for the consensus between the two raters was 0.79. In 22 children (49%)
      abnormalities were reported. Four patients (8.5%) had an arachnoid cyst. One
      female was diagnosed with a Chiari I malformation. Three children show enlarged
      Virchow-Robin spaces, an increased occurrence when compared to the normal
      population. CONCLUSIONS: A high rate of intracranial abnormalities was found in
      this study. Radiological findings do not contribute to the diagnosis of
      developmental disorders. However, young children with developmental disorders may
      not be able to express discomfort associated with brain abnormalities, such as a
      Chiari I malformation. Given the high prevalence of abnormalities in this sample
      neuroimaging may be a useful tool in clinically assessing children with
      developmental disorders.

PMID- 16616446
TI  - A preliminary analysis of trace elements in the scalp hair of patients with
      severe motor disabilities receiving enteral nutrition.
AB  - The concentrations of essential trace elements (copper, zinc, selenium,
      manganese, chromium, molybdenum, cobalt, and iodine) in the scalp hair of 21
      patients with severe motor disabilities receiving enteral nutrition were measured
      using inductively coupled plasma-mass spectrometry. Preliminary results show that
      copper, selenium, and molybdenum concentrations in the patients' hair were
      significantly lower than those in an age-matched control group (p<0.01). This
      suggests that intake of these elements may be reduced in patients receiving
      restricted enteral nutrition, although the clinical significance of these results
      should be discussed.

PMID- 16616447
TI  - A study of the cytotoxicity of branched-chain phytanic acid with mitochondria and
      rat brain astrocytes.
AB  - Phytanic acid, a saturated fatty acid of 20-carbon-atoms with isoprenoic
      structure, is formed from the phytol-side chain of chlorophyll in ruminants.
      Degradation of phytanic acid is blocked in Refsum disease by several enzymatic
      defects of peroxisomal degradation of branched-chain fatty acids. Refsum disease
      is an inherited neurological disorder progressively developing from early
      childhood to adultness. Clinical signs are attributed to toxicity of phytanic
      acid, which accumulates to unusually high levels in the tissue and serum of
      patients suffering from untreated Refsum disease. We report here that hippocampal
      astrocytes isolated from rat brain, which were exposed to phytanic acid (50
      microM) die within a few hours. In situ depolarization of mitochondria and an
      increase of cytosolic Ca2+ precede cell death. Therefore, we also investigated
      the influence of phytanic acid on physiology of mitochondria isolated from rat
      brain. Mitochondria become functionally impaired by phytanic acid, as indicated
      by uncoupling (resting state), inhibition of the electron transport (state 3),
      stimulation of ROS-generation, decline of Ca2+ loading and severe release of
      cytochrome c. Thus, phytanic acid seems to initiate astrocyte cell death by
      activating the mitochondrial route of apoptosis.

PMID- 16616448
TI  - Characterization of related impurities in megestrol acetate.
AB  - Three new compounds, 17alpha-acetoxy-2,6-dimethylpregna-1,4,6-triene-3,20-dione
      (1), 17alpha-acetoxy-2alpha,6-dimethylpregna-4,6-diene-3,20-dione (2), 17alpha
      acetoxy-6alpha-methoxylmethylpregna-4-ene-3,20-dione (3), together with five
      known ones, 17alpha-acetoxy-6beta-hydroxyl-6alpha-methylpregna-4-ene-3,20-dione
      (4), 17alpha-acetoxy-6alpha-hydroxyl-6beta-methylpregna-4-ene-3,20-dione (5),
      17alpha-acetoxy-pregna-4-ene-3,6,20-trione (6), 17alpha-acetoxy-pregna-4-ene-3,20
      dione (7) and 17alpha-acetoxy-6-methylene-pregna-4-ene-3,20-dione (8), were
      isolated and identified from the residual mother liquor of megestrol acetate.
      Their structures were established by spectroscopic methods. These compounds seem
      to be minor impurities in production of the drug megestrol acetate.

PMID- 16616449
TI  - Randomized clinical trial of an Internet-based versus brief office intervention
      for adolescent smoking cessation.
AB  - OBJECTIVE: Evaluation of novel treatment delivery methods, such as the Internet
      are notably absent from the adolescent smoking treatment literature. METHODS:
      Adolescent smokers ages 11-18 years were randomized to a clinic-based, brief
      office intervention (BOI; N=69) consisting of four individual counseling
      sessions; or to Stomp Out Smokes (SOS), an Internet, home-based intervention
      (N=70). Adolescents in SOS had access to the SOS site for 24 weeks. RESULTS: The
      30-day, point-prevalence smoking abstinence rates for BOI and SOS were 12% versus
      6% at week 24 and 13% versus 6% at week 36, with no significant treatment
      differences. Among participants who continued to smoke, SOS was associated with a
      significantly greater reduction in average number of days smoked than BOI
      (P=0.006). The BOI was found to be feasible with high session attendance rates.
      SOS participants accessed the site a mean+/-S.D. of 6.8+/-7.1 days. SOS use
      dropped to less than one-third of participants by week 3. CONCLUSION: Additional
      research is needed to tap the potential capabilities of the Internet for
      adolescent smoking cessation using proactive, personalized, patient-education
      components. PRACTICE IMPLICATIONS: Augmenting the SOS type of intervention with
      more structured, personal and proactive patient-education components delivered in
      person or by telephone or electronic mail is recommended.

PMID- 16616450
TI  - Randomized controlled trial of a social support ('buddy') intervention for
      smoking cessation.
AB  - OBJECTIVE: To assess the effectiveness of including a social support intervention
      ('buddy system') in a group treatment programme to aid smoking cessation.
      METHODS: Five hundred and sixty-three smokers attended groups at a smokers'
      clinic. These groups were randomized either to be (a) groups in which smokers
      were paired with another person to provide mutual support (buddy condition: n=237
      in 14 groups) or (b) to receive the same treatment without the buddy component
      (control: n=326 in 20 groups). Participants were seen weekly for the first 4
      weeks after stopping then followed up again after 26 weeks. RESULTS: Smokers in
      the buddy condition were no more likely than smokers in the control condition to
      stay abstinent at 1, 4 or 26 weeks. The effect was in the right direction at week
      one post-quit but after controlling for potential confounders the difference was
      not significant (odds ratio=1.45 (95% CI; 0.92-2.29), p=0.06). CONCLUSIONS: We
      were unable to show that a buddy system improved abstinence rates of group
      treatment programmes. This might be due to the high level of social support
      already achieved through the groups. PRACTICE IMPLICATIONS: The buddy system is a
      simple and very low cost addition to a group treatment programme; but the results
      from this study suggest that the kind of buddy system tested may not add
      substantially to the success rates. However there may be merits in a more
      intensive or protracted form of buddying.

PMID- 16616451
TI  - Single centre experience of liver resection for hepatocellular carcinoma in
      patients outside transplant criteria.
AB  - INTRODUCTION: To report analysis of our results of liver resection for HCC
      outside the transplant criteria with preserved liver function. METHODS: Between
      January 1990 and March 2005, 279 patients with HCC were seen at our institution
      and entered into a prospective database. There were 51 patients who did not
      fulfill the transplant criteria and underwent partial hepatectomy. Survival was
      determined by Kaplan-Meier analysis. RESULTS: The median tumour size was 10.0 cm
      with a range of 3-20 cm. Twenty-nine patients had solitary tumours and 21
      patients had two or more liver tumours, with four patients whose tumours were
      less than 5 cm in maximal diameter. Ten patients had bilobar disease. The 30-day
      mortality was 8%. The 1-, 3- and 5-year overall survival was 63, 40 and 33%,
      respectively, and the median survival was 16.6 months. Fifteen potential
      variables were analysed as potential predictors of adverse outcome. Multivariate
      analysis showed Child-Pugh classification, presence of cirrhosis, rupture on
      presentation and tumour histology to be independent prognostic factors on
      survival. CONCLUSION: Partial hepatectomy in patients with advanced HCC who are
      ineligible for transplantation can be performed safely and can achieve a 5-year
      survival of 33%.

PMID- 16616452
TI  - Exploring the boundary between temperament and generalized anxiety disorder: a
      receiver operating characteristic analysis.
AB  - Studies of individuals with an increased tendency to experience negative emotions
      such as fear, sadness, and anger have documented links between this temperamental
      trait and anxiety disorders. There exists debate, however, concerning the degree
      to which high levels of a temperamental trait are a necessary and/or sufficient
      component of a DSM diagnosis. In this study, receiver operating characteristic
      (ROC) analyses assessed the relations between levels of harm avoidance (HA) and
      generalized anxiety disorder (GAD) diagnoses in 334 children and their parents.
      Analyses revealed HA scores to be highly predictive of GAD diagnoses in children
      (AUC=.791, P<.001) and adults (AUC=.818, P<.001). However, there were many
      individuals with high HA scores who did not qualify for a GAD diagnosis. These
      findings suggest that while there are strong associations between HA and GAD,
      high levels of HA are neither necessary nor sufficient in the formation of
      clinically significant anxiety symptoms.

PMID- 16616453
TI  - Use of 65 kDa mannoprotein gene primers in Real Time PCR identification of
      Candida albicans in biological samples.
AB  - A method for the detection and quantification of Candida albicans in biological
      samples (blood, urine and serum) was developed with the use of Real-Time PCR
      utilizing CaMP65-specific primers. Two different systems were used for the
      detection in the LightCycler platform (Roche): the SYBR green fluorescent dye
      with melting peak analysis and the 5'nuclease fluorescent-probe detection. The
      amplification was highly specific for C. albicans, providing no cross-reaction on
      genomic DNA extracted from other Candida species or Aspergillus. The sensitivity
      in simulated biological samples was especially high (1 genome) when applied to
      sera and urine, and in blood samples the limit of detection was higher by ten
      fold. Finally, the real-time PCR was employed in order to detect and quantify C.
      albicans in the sera from patients with invasive candidiasis.

PMID- 16616454
TI  - Global and configural visual processing in adults with autism and Asperger
      syndrome.
AB  - This study was designed to explore how adults with autism and Asperger syndrome
      (ASD) would visually process compound figures. They were tested in two tasks, one
      involving hierarchical global/local stimuli, the other involving face-like or
      geometrical stimuli where the processing of the inter-elemental spatial
      relationships was emphasized. Adults with ASD showed, like controls, a preference
      for the global level of the hierarchical stimuli. With the stimuli involving
      inter-elemental spatial relationship manipulations, the adults with ASD showed a
      preference for local elements, whereas controls did not show a preference. This
      supports earlier findings from children with ASD, suggesting that though
      individuals with autism may process global aspects of stimuli in priority, they
      tend to specific aspects in stimuli containing both local and configural
      elements.

PMID- 16616455
TI  - Behavioral effects of a neurotoxic compound isolated from Clibadium surinamense L
      (Asteraceae).
AB  - Clibadium surinamense L, popularly known as cunambi, is a native plant from the
      Northern region of Brazil illegally used for predatory fishing. Previous results
      from our laboratory have demonstrated that the oral treatment of mice with the
      ethanolic extract (EE) of the leaves of the plant induced generalized tonic
      clonic seizures followed by death within 30 min. The aims of the present paper
      were to characterize the convulsant effect of the hexanic extract (HE) of the
      stems and leaves of C. surinamense and, by bioguided purification, to identify
      the active principle and its mechanism of action. The leaves and stems were
      extracted with hexane (100 g/L) in Soxhlet for 36 h (yield of 2.4%), the solvent
      was evaporated and the powder dissolved in 1.5% saline/Tween 80. Male mice (30-35
      g) treated with HE (22.5-360 mg/kg, p.o.) showed behavioral alterations
      consistent with CNS stimulation. The intensity and duration of the effect were
      proportional to the administered doses. The behavioral alterations, measured with
      a graded score of seizure severity, revealed that pretreatment with carbamazepine
      (30 mg/kg, i.p., 60 min) or phenytoin (50 mg/kg, i.p., 30 min) did not alter the
      HE convulsive effect. In contrast, phenobarbital (30 mg/kg, i.p., 60 min) or
      diazepam (2 mg/kg, i.p., 30 min) reduced the HE effect, increasing the ED(50) for
      clonic seizures from 64.4 to 89.8 mg/kg and 168.9 mg/kg, respectively.
      Purification of the HE in a silica gel column eluted with a hexane/ethyl acetate
      gradient yielded a single fraction with convulsant effect in which cunaniol
      acetate was identified by (1)H NMR as the main active compound. These results
      indicated that inhibition of GABAergic transmission by cunaniol acetate might be
      responsible for the convulsant effects of C. surinamense L in mice, but do not
      exclude a direct cunaniol action labilizing neuronal excitability.

PMID- 16616456
TI  - AKT can be activated in the nucleus.
AB  - To investigate issues about AKT/PKB nuclear localization in cells, we examined
      endogenous or transiently transfected AKT localization in cancer cell lines by
      immunofluorescence. We found that AKT can be detected in both the nucleus and
      cytoplasm of HEK 293, HeLa and MCF7E cells. It was found that an active process
      mediates AKT nuclear translocation as shown by fusing AKT with GFP3 protein. The
      cellular distribution pattern of serial deletion mutants from GFP3-HA-AKT
      revealed that more than one segment of AKT is required for AKT nuclear
      translocation, while the individual segment does not have any apparent nuclear
      transport activity. These results implied that the signal mediating AKT nuclear
      translocation is conformation dependent, or more likely, is dependent upon
      association with other proteins. It was also found that AKT does not contain any
      apparent nuclear export signal. Furthermore, we found that nuclear AKT was
      activated in MCF7E cells upon stimulation. The possibility that nuclear activated
      AKT was translocated from the cytoplasm was excluded through the generation of a
      chimeric AKT protein, in which a strong nuclear localization signal was fused to
      the C-terminal of AKT.

PMID- 16616458
TI  - Genetic analysis of the human ENTH (Epsin 4) gene and schizophrenia.
AB  - Numerous linkage studies suggest that chromosome 5q may be one of the important
      cytogenetic regions containing risk loci for schizophrenia susceptibility.
      Recently, genetic variations (rs254664 and rs10046055) in the intron 1 and 5'
      flanking regions of the ENTH (also known as Epsin 4) gene, which is located in 5q
      33.3, have been demonstrated to be significantly associated with schizophrenia.
      The present study investigates whether this finding could be replicated in a
      population of Han Chinese, consisting of 269 patients with schizophrenia and 236
      normal controls, by analyzing 9 single nucleotide polymorphisms (SNPs) ranging
      from the 5' upstream region to intron 8 of the ENTH gene and covering 96 kb. The
      results showed that we failed to identify the associations of rs1186922 and
      rs10046055 with schizophrenia. Although another genetic variation (rs1186922)
      showed a weak association with schizophrenia (uncorrected p value for alleles =
      0.038), the significance did not survive after Bonferroni correction. This study
      thus fails to support an association of genetic variations in the ENTH gene and
      schizophrenia.

PMID- 16616459
TI  - Tolerance induced by chronic inhaled antigen in a murine asthma model is not
      mediated by endotoxin.
AB  - Ovalbumin (OVA)-sensitized wildtype (WT) and endotoxin-resistant (ER) mice
      developed similar degrees of airways eosinophilia and serum OVA-specific IgE
      levels after acute aerosolized OVA challenge. WT mice demonstrated methacholine
      hyperreactivity, whereas ER mice showed no change in responsiveness. With chronic
      aerosolized OVA challenge, both WT and ER mice developed local tolerance, with
      resolution of airway eosinophilia but persistence of anti-OVA IgE in serum. Thus,
      the development of local tolerance with chronic aerosol exposure to OVA is
      independent of any potential effects of endotoxin in the OVA aerosol solution.

PMID- 16616457
TI  - FSH signaling pathways in immature granulosa cells that regulate target gene
      expression: branching out from protein kinase A.
AB  - Follicle-stimulating hormone (FSH) is necessary and sufficient to induce
      maturation of ovarian follicles to a mature, preovulatory phenotype in the intact
      animal, resulting in the generation of mature eggs and production of estrogen.
      FSH accomplishes these actions by inducing a complex pattern of gene expression
      in target granulosa cells that is regulated by input from many different
      signaling cascades, including those for the extracellular regulated kinases
      (ERKs), p38 mitogen-activated protein kinases (MAPKs), and phosphatidylinositol-3
      kinase (PI3K). The upstream kinase that appears to be responsible for initiating
      all of the signaling that regulates gene expression in these epithelial cells is
      protein kinase A (PKA). PKA not only signals to directly phosphorylate
      transcription factors like cAMP response element binding protein and to promote
      chromatin remodeling by phosphorylating histone H3, this versatile kinase also
      enhances the activity of the p38 MAPK, ERK, and PI3K pathways. Additionally,
      accumulating evidence suggests that activation of a single signaling cascade
      downstream of PKA is not sufficient to activate target gene expression. Rather,
      cross-talk between and among signaling cascades is required. We will review the
      signaling cascades activated by FSH in granulosa cells and how these cascades
      contribute to the regulation of select target gene expression.

PMID- 16616460
TI  - Layer-by-layer polyelectrolyte coating of low molecular weight poly(lactic acid)
      nanoparticles.
AB  - Low molecular weight (M(w)) poly(L-lactic acid) (PLA) nanoparticles were coated
      with polyelectrolytes (PEs) by layer-by-layer (LbL) technique using a filtration
      approach. Poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) were
      applied as PEs in coating. LbL coating is aimed to use in producing
      (nano)particulate drug delivery systems with improved biocompatibility and
      sustained or targeted release of drug substances. Nanoparticles of rapidly
      biodegradable polymers, like the low M(w) PLA, open up a possibility to control
      the release of the encapsulated substance by the coating, but set challenges to
      the coating process due to increased aggregation tendency and degradation rate of
      the polymer. When the core PLA nanoparticles were prepared by nanoprecipitation,
      surface properties of the nanoparticles were affected by solvent selection.
      Successful LbL coating of the PLA nanoparticles was obtained only with
      chloroform, but not with dichloromethane as the solvent during nanoprecipitation.
      Reason for this was found to be the more charged surface of the nanoparticles
      prepared with chloroform compared to the nanoparticles prepared with
      dichloromethane.

PMID- 16616461
TI  - Physicochemical and functional characterization of a biosurfactant produced by
      Lactococcus lactis 53.
AB  - Isolation and identification of key components of the crude biosurfactant
      produced by Lactococcus lactis 53 was studied. Fractionation was achieved by
      hydrophobic interaction chromatography which allowed the isolation of a fraction
      rich in glycoproteins. Molecular (by Fourier transform infrared spectroscopy) and
      elemental compositions (by X-ray photoelectron spectroscopy) were determined.
      Critical micelle concentration achieved for the isolated fraction was 14 g/l,
      allowing for a surface tension value of 36 mJ/m(2). Moreover, the isolated
      fraction, stable to pH changes between 5 and 9, was found to be an anti-adhesive
      and antimicrobial agent against several bacterial and yeast strains isolated from
      explanted voice prostheses, even at low concentrations. Further purification
      steps should be carefully analyzed as each purification step will increase the
      costs and decreases the amounts of biosurfactants recovered.

PMID- 16616462
TI  - Can 29kDa rhGM-CSF expressed by silkworm pupae bioreactor bring into effect as
      active cytokine through orally administration?
AB  - In order to study the effect of human granulocyte-macrophage colony-stimulating
      factor (hGM-CSF) as active cytokine through orally administration, we expressed
      hGM-CSF within silkworm pupae bioreactor. The purified rhGM-CSF named as BmrhGM
      CSF is characterized as 29kDa glycoprotein, and its biological activity was
      measured both in vitro and in vivo. We found out BmrhGM-CSF could stimulate the
      colony formation of human bone marrow cells in a dose-dependent manner whether
      which were treated with or without gamma-ray 24h before. The ability of colony
      formation induced by BmrhGM-CSF is negatively correlated with gamma-ray
      intensity. As soon as 15min post oral administration with BmrhGM-CSF labeled with
      (125)I, an approximately 20kDa protein fragment was detected within mice blood by
      SDS-PAGE followed by autoradiography. In blood sample of test mice, a protein was
      also recognized by anti-hGM-CSF antibody using ELISA. The immunohistochemical
      analysis showed that BmrhGM-CSF was detected within intestinal histiocyte. This
      indicated it might be absorbed into blood via intestinal microvillus.
      Pharmacokinetics analysis after orally administered BmrhGM-CSF in animal model of
      leucopenia including mice, Beagle dogs and macaques showed that: (1) BmrhGM-CSF
      promoted the CFU-S formation in mice spleen and the synthesis of DNA in bone
      marrow cells of mice; (2) BmrhGM-CSF induced bone marrow karyocyta granulocyte
      growth significantly in both macaques and Beagle dogs compared to the negative
      control group. On the 9th day of orally administration, the animal WBC
      significantly increased in a dose-dependant manner, in which neutrophilic
      granulocyte was predominant. The WBC level of dogs in high dose group was about
      1.5x10(9)cells/L more than that in the negative control. And the bone marrow
      smear revealed that the percents of both myloblast and progranulocyte in WBC in
      the hGM-CSF group were obviously higher than those in the negative control. These
      results proved that BmrhGM-CSF, a 29kDa glycoprotein expressed by Silkworm pupae
      bioreactor, could bring into the effect as active cytokine through oral
      administration.

PMID- 16616463
TI  - [Pilot epidemiologic study of transmission of cytomegalovirus from mother to
      preterm infant by breastfeeding].
AB  - Transmission of cytomegalovirus (CMV) infection from mothers to preterm infants
      during breastfeeding may be symptomatic and long term consequences are unknown.
      This study evaluated the kinetics of CMV load in breastmilk and the rate of
      postnatal CMV transmission via breastmilk from mothers to their preterm infants.
      METHODS: Prospective study of mother-child pairs after preterm delivery before 33
      weeks. Exclusion of donor breast milk and of CMV-seropositive blood products.
      Material used was maternal CMV serostatus, ear swab of the infant at birth,
      weekly screened breast milk and children's urine by rapid viral culture. RESULTS:
      During a 5-month period 28 mother-infant pairs with 34 preterm infants were
      studied. Eighteen women (64.3%) were CMV-seronegative at birth; breastmilk
      samples and the infants' urine remained CMV-negative. Eight of the 10
      seropositive mothers, who had 11 preterm infants, excreted CMV into breast milk
      (80%). CMV excretion into breast milk was detected during the first week after
      delivery in 66% cases and was at its peaked between 3 to 5 weeks after delivery.
      Out of the 7 CMV-exposed infants, CMV transmission was confirmed in only one
      asymptomatic case. Total quantity of breast milk intake did not seem
      discriminative for CMV transmission. CONCLUSION: In CMV-seropositive mothers of
      preterm infants a high incidence of CMV excretion into breast milk was detected.
      Despite this high rate, symptomatic infection did not occur. However, potential
      risk and severity of infection may be difficult to establish. Because
      breastfeeding is beneficial, new procedures for gentle virus inactivation of
      seropositive breast milk should be assessed.

PMID- 16616464
TI  - [How to discuss death with a dying child: a story can help?].
AB  - Is it necessary - and possible - to discuss death with a child in palliative
      phase? How should one approach the subject? A recent Swedish study demonstrated
      the benefits for parents who discussed with their child his or her imminent
      death, and raised the question of the role nursing can play to help parents. The
      mother of one child treated in our unit recently wrote a story 48 hours before
      the child's death. The story served to broach a number of recurrent questions
      often raised by dying children and their families: fear of the unknown, of being
      replaced, the inevitability of death, grief, and fear of being forgotten... The
      story was given to 13 families with dying children. In order to evaluate the
      story's impact on families and to determine whether a document which stimulates
      dialogue should continue to be given to parents, we asked that they fill out a
      questionnaire. Fifty-five percent of parents answered, and confirmed that the
      story was experienced as a positive thing and helped parents to talk with their
      children. This study raises many questions and should be part of a global
      accompaniment strategy. A review of medical, general and children's literature,
      as well the results of our study, lead us to conclude that the medical body
      should lend its full support to families who wish to engage in this dialogue with
      their children.

PMID- 16616465
TI  - Effect of L-carnitine supplementation on xenobiotic-metabolizing hepatic enzymes
      exposed to methanol.
AB  - The study aimed to evaluate the effect of L-carnitine on hepatic cytochrome P450
      dependent monooxygenases exposed to methanol. Male Spraque-Dawley rats were given
      methanol (1/4 LD50 and 1/2 LD50) together with L-carnitine (1g/kg body weight).
      The parameters of microsome electron transport chains I and II and the levels of
      CYP2E1, CYP2B1/2 and CYP1A2 were measured 8, 12, 24, 48, 72 and 96 h after
      exposure. L-carnitine did not affect cytochrome P450 but it significantly
      increased at 72 and 96 h NADPH-cytochrome P450 reductase. It stimulated
      cytochrome b5 at 48 and 96 h and NADH-cytochrome b5 reductase activity at 12, 72
      and 96 h. Methanol, especially the lower dose, inhibited cytochrome P450 after 48
      h, but the higher methanol dose inhibited NADH-cytochrome b5 reductase activity
      in this time. L-carnitine, combined with the lower dose of methanol, stimulated
      NADPH-cytochrome P450 reductase after 48 h and cytochrome b5 and NADH-cytochrome
      b5 reductase over the whole period of observation. L-carnitine stimulated
      CYP2B1/2 but not CYP2E1 and CYP1A2. Methanol stimulated CYP2E1 at 24 h, but
      CYP1A2 at 96 h in the studied doses. CYP2B1/2 was induced by the lower dose of
      methanol at 24 h but by the higher one at 96 h. When given together, L-carnitine
      and methanol (1/2 LD50) significantly stimulated CYP2E1 up to 170% at 24 h and
      145% at 96 h.

PMID- 16616466
TI  - Lipid peroxidation and HSP72/73 expression in rat following cadmium chloride
      administration: interactions of magnesium supplementation.
AB  - OBJECTIVE: to determine whether magnesium (Mg) supplementation could have a
      protective effect against the cadmium (Cd)-induced oxidative stress in liver,
      kidneys and testes of adult male rats. Stress was evaluated by measuring lipid
      peroxidation by thiobarbituric acid reactive substances (TBARS) and the heat
      shock protein (HSP) 72/73 expression. CdCl2 injections (2.5mg/day/kg body weight)
      for 10 days resulted in a time dependent increase of Cd accumulation in liver,
      kidney and testes, the highest levels being found in liver (400 microg/g dried
      tissue). At the same time, an increase of lipid peroxidation was observed. The
      effect was maximal at day 1 of Cd treatment in liver and testes, and later (day
      5) in kidney. Then, Cd-induced lipid peroxidation decreased, suggesting the
      activation of antioxidant defense mechanisms. Injections of Mg SO4 (300-600
      mg/day/kg body weight) reduced in a dose-dependent manner Cd-induced lipid
      peroxidation in liver and kidney as well as the accumulation of Cd in liver,
      kidney and testes. In testes, a protective effect of Mg was found only during the
      early phase of Cd-poisoning. On days 5 and 10, lipid peroxidation was even
      increased as compared to controls. In liver and testes only the constitutive
      HSP73 was detected whereas in kidney both HSP73 and the inducible HSP72 were
      expressed. HSP72/73 expression was not significantly increased by Cd and HSP73
      was even lowered in kidney, probably due to the strong dose used. These results
      were not modified by Mg injections. CONCLUSION: Mg supplementation can reduce Cd
      accumulation in organs and lipid peroxidation related to Cd administration.

PMID- 16616467
TI  - Nematodes of the genus Pristionchus are closely associated with scarab beetles
      and the Colorado potato beetle in Western Europe.
AB  - Evolutionary developmental biology examines how changes in developmental
      programmes give rise to developmental and, ultimately, morphological novelty. To
      this end, comparisons of related but distinct organisms have to be performed. The
      diplogastrid nematode Pristionchus pacificus has been developed as a satellite
      system for a detailed comparison of various developmental processes to the model
      organism Caenorhabditis elegans, a rhabditid nematode. In addition to
      developmental and genetic studies, a genomic platform has been established to
      analyse the biology of this organism. However, only little is known about where
      and how Pristionchus pacificus and its relatives live in the wild. Here we show
      that nematodes of the genus Pristionchus live in close association with
      scarabaeoid beetles and the Colorado potato beetle. In total, we generated 371
      isogenic female lines from 4242 beetles collected at 25 sampling sites all over
      Europe. Isogenic female lines were subjected to sequence analysis and mating
      experiments for species determination. The 371 isolates fell into six species.
      Two hermaphroditic species account for about 60% of the collected nematodes. We
      found Pristionchus maupasi almost exclusively on cockchafers and Pristionchus
      entomophagus predominantly on dung beetles. Colorado potato beetles carried the
      gonochoristic species Pristionchus uniformis, which was only rarely observed on
      scarabaeoid beetles. We describe the initial evidence for the association of
      Pristionchus nematodes with beetles and provide a phylogeny based on sequence
      analysis of the small subunit ribosomal RNA gene.

PMID- 16616468
TI  - Normal embryonic development of the Japanese pipistrelle, Pipistrellus abramus.
AB  - The normal embryonic development of the Japanese pipistrelle, Pipistrellus
      abramus was described. A total of 13 stages between the early pharyngula and the
      embryo just before birth were established, based on external morphological
      features of 33 embryonic specimens. To aid embryological comparison between
      chiropteran lineages, the stage numbers used in the Carollia perspicillata
      embryonic staging system (Cretekos et al., 2005) were applied to each embryonic
      stage of P. abramus. The size (crown-rump length, CRL) of P. abramus embryos
      became larger throughout ontogeny at a relatively constant rate. When the CRL of
      embryos was compared in each morphologically corresponding embryonic stage, the
      CRL of P. abramus was always smaller than that of C. perspicillata. The overall
      nature of organogenesis was almost similar in both P. abramus and C.
      perspicillata. Species-specific differences in bats were observed at later stages
      of embryogenesis, notably in the craniofacial and tail regions.

PMID- 16616469
TI  - Immunological synapse and microclusters: the site for recognition and activation
      of T cells.
AB  - An immunological synapse (IS) is formed at the interface between antigen
      presenting cells and T cells, and is believed to be the structure responsible for
      antigen recognition and T-cell activation. However, recent imaging analyses
      reveal that T-cell receptor microclusters (MCs) formed prior to IS are the site
      for antigen recognition and T-cell activation. MCs are continuously generated at
      the periphery of the interface, even after IS formation, and induce sustained
      activation signals. MC formation is not accompanied by lipid-raft clustering.
      Central supramolecular activation cluster is considered functional in recycling
      and degradation of T-cell receptors, directional secretion of cytokines and
      cytolytic granules, generation of sustained signals, or maintenance of the cell
      cell conjugation.

PMID- 16616470
TI  - Genetic and epigenetic regulation of IgH gene assembly.
AB  - Precursor B cells assemble a diverse repertoire of immunoglobulin (Ig) genes by
      the process of V(D)J recombination. Assembly of IgH genes is regulated in a
      tissue- and stage-specific manner via the activation and then the inactivation of
      distinct regions within the one megabase IgH locus. Recent studies have shown
      that regional control is achieved using a combination of genetic and epigenetic
      strategies, which modulate chromatin accessibility to V(D)J recombinase, relocate
      IgH loci within the nucleus, and promote changes in locus conformation that alter
      the spatial proximity of target gene segments. Orchestration of these regulatory
      processes is crucial for the generation of a functional B cell repertoire.

PMID- 16616472
TI  - Expanding the effector CD4 T-cell repertoire: the Th17 lineage.
AB  - The Th1/Th2 paradigm has provided the framework for understanding CD4 T-cell
      biology and the interplay between innate and adaptive immunity for almost two
      decades. Recent studies have defined a previously unknown arm of the CD4 T-cell
      effector response--the Th17 lineage--that promises to change our understanding of
      immune regulation, immune pathogenesis and host defense. The factors that specify
      differentiation of IL-17-producing effector T-cells from naive T-cell precursors
      are being rapidly discovered and are providing insights into mechanisms by which
      signals from cells of the innate immune system guide alternative pathways of Th1,
      Th2 or Th17 development.

PMID- 16616471
TI  - Programming CD8+ T cells for effective immunotherapy.
AB  - The differentiation state of CD8+ T cells has emerged as a crucial determinant of
      their ability to respond to tumor and infection. Signals from T-cell receptors,
      co-stimulatory molecules and cytokine receptors direct the differentiation
      process. These signals 'program' sustained and heritable gene expression patterns
      that govern progressive differentiation and lineage commitment. The epigenetic
      mechanisms by which T cells are programmed are just beginning to be elucidated.
      Understanding the mechanisms that control CD8+ T-cell differentiation is
      important in the development of novel immunotherapy strategies.

PMID- 16616473
TI  - Ig class switching: targeting the recombinational mechanism.
AB  - Recent studies have provided insights into the mechanisms involved in targeting
      antibody gene class switch recombination (CSR) to various switch DNA regions
      located upstream of constant region genes. Targeting appears to involve sequence
      motifs that are favored for deoxycytosine deamination by the activation-induced
      deaminase enzyme that is required for CSR, together with transcription (and in
      some cases R-loop formation) to provide the single-stranded DNA needed for
      activation-induced deaminase activity. There is also another poorly understood
      mechanism that limits CSR to a specific length of DNA downstream of the switch
      region transcriptional promoter.

PMID- 16616474
TI  - B cell recognition of membrane-bound antigen: an exquisite way of sensing
      ligands.
AB  - B cell recognition of membrane-bound antigens leads to the formation of an
      immunological synapse and efficient B cell activation. Ongoing research has been
      directed towards identifying the parameters that regulate this process.
      Furthermore, considerable attention has also been focused on the cell types that
      mediate presentation of intact antigens to B cells, as well as on the mechanisms
      that underlie it. Whilst there are still many unanswered questions, recent
      developments in these areas begin to shed light on an emerging field.

PMID- 16616475
TI  - Memory T cell recruitment to the lung airways.
AB  - Memory T cells play an important role in the resolution of secondary respiratory
      virus infections through the production of anti-viral cytokines and the lysis of
      infected cells. Within the lung airways, memory T cells form an initial line of
      defense against secondary virus challenge by limiting early viral replication at
      the site of infection. Recent studies have addressed the generation and
      maintenance of airway memory T cells and their relationship with memory T cells
      in the secondary lymphoid organs. These advances have demonstrated that different
      memory subsets contribute to the maintenance of the airway memory T cell
      population and have identified molecules that influence trafficking to the lung
      tissue and the lung airways.

PMID- 16616476
TI  - The role of CD8 T cells in innate immunity and in antigen non-specific
      protection.
AB  - The role of CD8 T cells in adaptive immune responses is well understood. These
      lymphocytes respond through their T cell receptors to diverse antigens presented
      by MHC class I molecules by proliferating, secreting cytokines and chemokines,
      and directly lysing infected cells. Recently, a role for CD8 T cells in the
      innate immune response has become apparent. Independent of T cell receptor
      ligation, CD8 T cells can mount a response against pathogens by secreting
      cytokines and can defend against tumors by directly killing transformed cells.
      This innate response has been shown to be beneficial in controlling several types
      of bacterial infections. However, a subset of CD8 T cells that have innate non
      antigen-specific capabilities has been implicated in self-reactivity, which could
      lead to autoimmunity.

PMID- 16616477
TI  - Somatic hypermutation: subverted DNA repair.
AB  - Somatic hypermutation generates high-affinity antibodies of different isotypes
      that efficiently protect us against a plethora of pathogens. Recent analyses of
      the types of mutations produced in gene-deficient mice have indicated how DNA
      repair proteins are drawn into the pathway. Activation-induced cytosine deaminase
      begins the process by deaminating cytosine to uracil in DNA. The uracils are then
      recognized by the base excision repair protein uracil DNA glycosylase and by the
      mismatch repair proteins MutS homologue 2 and MutS homologue 6. Instead of
      repairing the uracils, these proteins attract low fidelity DNA polymerases, which
      synthesize nucleotide substitutions at an unprecedented level.

PMID- 16616478
TI  - Stromal niches, plasma cell differentiation and survival.
AB  - Contacts made with other cells and stroma have a major impact on proliferation,
      differentiation, survival, migration and immunoglobulin class switching of plasma
      cell precursors as well as on the lifespan of the antibody-secreting cells.
      Induction of tissue-specific chemokine receptors and adhesion molecules directs
      migratory plasma cell precursors to tissues close to those in which the original
      immune stimulation occurred. This mechanism focuses the production of specific
      antibodies within a particular type of tissue, thus providing a means for the
      most efficient protection against tissue-specific pathogens. Relocation does not
      apply to long-lived plasma cells responsible for sustained titers of high
      affinity systemic antibody. These are formed in germinal centers and migrate to
      specific niches in the bone marrow that support their further differentiation and
      long-term survival.

PMID- 16616479
TI  - Protein arginine methylation in lymphocyte signaling.
AB  - Methylation of arginine is an additional option within the repertoire of post
      translational modifications that proteins utilize for their communication with
      other partner proteins and nucleic acids, which ultimately contributes to
      cellular functions. Recent studies reveal that protein arginine methylation is
      more common and widespread than previously thought and that it is implicated in a
      number of key cellular processes including signal transduction. Two recent
      investigations have propelled this new world of protein modification into the
      immunological community by showing that TCR and CD28 signaling exploit this
      pathway. In contrast to other protein modifications utilized in intracellular
      signaling, arginine methylation seems to be long-lasting, raising interesting
      questions as to when, where and for what reason it can be utilized in the
      lymphocyte differentiation processes.

PMID- 16616480
TI  - Silencing of autoreactive B cells by anergy: a fresh perspective.
AB  - B-cell antigen receptor (BCR) signals are crucial for initiation of humoral
      immune responses and must be actively modulated and/or terminated in preparation
      for receipt of subsequent cues for progression. BCR signaling is also actively
      inhibited in autoreactive cells in which unresponsiveness is maintained by
      anergy. This serves to prevent cell activation and autoimmunity. Importantly, the
      feedback mechanisms that modulate and/or terminate signaling during normal
      antigen-induced B-cell activation appear to also be involved in maintaining B
      cell anergy. In fact, it is suggested that anergy reflects nothing more than the
      normal inability of cells to respond to antigen following preceding stimulation
      of normal inhibitory feedback mechanisms. Thus, the time-honored two-signal
      hypothesis is almost certainly correct, with second signals being required to
      release the cell from inhibitory BCR-specific and trans-active feedback
      regulation.

PMID- 16616481
TI  - Treg control of antimicrobial T cell responses.
AB  - Immunity to microbes depends on the function of numerous cell types and their
      products. These include T cells with regulatory function (Treg) against the
      components of the immune system. Recently, there has been much discussion
      regarding the circumstances in which protective or tissue-damaging T cell
      responses to microbes are affected by the activity of Treg. These relationships
      range from situations in which the Treg response seems to contribute to immune
      dysfunction to those that minimize tissue damage caused by immunoinflammatory T
      cell reactions. In several parasitic infections, Treg maintain equilibrium to
      ensure parasite persistence, minimal tissue damage and immunity to re-infection.
      Recently, several unresolved questions about the role of Treg in microbial
      infections have been raised and discussed. Learning how to successfully
      manipulate Treg responses could result in more effective vaccines and
      immunomodulators.

PMID- 16616482
TI  - Inflammatory response to exercise in COPD.

PMID- 16616483
TI  - Antibiotic prescribing in Australian general practice: how has it changed from
      1990-91 to 2002-03?
AB  - There is increasing evidence that antibiotics have limited value for many
      respiratory illnesses. This study investigates changes in overall antibiotic
      prescribing rates, and rates for specific conditions, by Australian general
      practitioners (GPs) between 1990-91 and 2002-03. This is a comparative study of
      two cross-sectional surveys of general practice activity, the Australian
      Morbidity and Treatment Survey (AMTS) 1990-91 and Bettering Evaluation and Care
      of Health (BEACH) 2002-03. Both studies used random samples of GPs, each
      providing data about a cluster of patient encounters. Outcome measures are the
      antibiotic prescribing rate per 100 encounters or per 100 selected problems
      managed. Between 1990-91 and 2002-03, the overall antibiotic prescribing rate
      decreased 24.3% from 18.9 prescriptions per 100 encounters to 14.3 (P<0.001). For
      children, the decrease for acute upper respiratory tract infection (URTI) was
      from 39.0 per 100 URTI problems to 24.4 (P<0.001), while the antibiotic
      prescribing rate increased for acute otitis media, decreased for
      bronchitis/bronchiolitis, and remained unchanged for other respiratory problems
      analysed. For adults the antibiotic prescribing rate for URTI decreased from 58.2
      per 100 URTI problems to 40.0 (P<0.001), increased significantly for sinusitis
      and remained unchanged for all other respiratory problems. Antibiotic prescribing
      decreased significantly between 1990-91 and 2002-03 but the decrease was
      selective. The decline has been more pronounced among children than adults, and
      particularly for URTI. While the message of educators may be achieving its goal
      for URTI, other approaches targeting specific respiratory problems may be
      required to reduce antibiotic prescribing in these areas.

PMID- 16616484
TI  - Application of complement 1q for the site-selective recognition of immune complex
      in protein chip.
AB  - Complement 1q (C1q) was applied for the specific recognition of antibody-antigen
      complex in antibody-based protein chip. The specific binding of C1q to antibody
      antigen complex was investigated by surface plasmon resonance (SPR) with respect
      to Yersinia entericolitica, Salmonella typimurium, insulin, and bovine serum
      albumin. The protein chip was fabricated with two different kinds of antibodies a
      zigzag configuration. When one of antigens and fluorescein-isothiocyanate (FITC)
      labeled C1q was applied on the protein chip, the specific binding event of C1q to
      immune complexes formed on protein chip was observed by fluorescence microscopy.
      These results implicate that the C1q can be used as an alternative to many
      antibodies that may be utilized individually on each spot of the protein chip.

PMID- 16616485
TI  - Amperometric glucose biosensor based on polymerized ionic liquid microparticles.
AB  - A glucose amperometric biosensor based on the immobilization of glucose oxidase
      (GOx) in microparticles prepared by polymerization of the ionic liquid 1-vinyl-3
      ethyl-imidazolium bromide (ViEtIm+ Br-) using the concentrated emulsion
      polymerization method has been developed. The polymerization of the emulsion
      dispersed phase, in which the enzyme was dissolved together with the ionic liquid
      monomer, provides poly(ViEtIm+ Br-) microparticles with entrapped GOx. An anion
      exchange reaction was carried out for synthesizing new microparticles of
      poly(ViEtIm+ (CF3SO2)2N-) and poly(ViEtIm+ BF4-). The enzyme immobilization
      method was optimized for biosensor applications and the following optimal values
      were determined: pH 4.0 for the synthesis medium, 1.23 M monomer concentration
      and 3.2% (w/w) cross-linking content. The performance of the biosensor as a
      function of some analytical parameters such as pH and temperature of the
      measuring medium, and enzymatic load of the microparticles was also investigated.
      The effect of the substances which are present in serum samples such as uric and
      ascorbic acid was eliminated by using a thin Nafion layer covering the electrode
      surface. The biosensor thus prepared can be employed in aqueous and in non
      aqueous media with satisfactory results for glucose determination in human serum
      samples. The useful lifetime of this biosensor was 150 days.

PMID- 16616486
TI  - Using the stress response to monitor process control: pathways to more effective
      bioremediation.
AB  - Environmental contamination with a variety of pollutants has prompted the
      development of effective bioremediation strategies. But how can these processes
      be best monitored and controlled? One avenue under investigation is the
      development of stress response systems as tools for effective and general process
      control. Although the microbial stress response has been the subject of intensive
      laboratory investigation, the environmental reflection of the laboratory response
      to specific stresses has been little explored. However, it is only within an
      environmental context, in which microorganisms are constantly exposed to multiple
      changing environmental stresses, that there will be full understanding of
      microbial adaptive resiliency. Knowledge of the stress response in the
      environment will facilitate the control of bioremediation and other processes
      mediated by complex microbial communities.

PMID- 16616487
TI  - RECIST revisited: a review of validation studies on tumour assessment.
AB  - The response evaluation criteria in solid tumours (RECIST) was developed in the
      late 1990s to replace the WHO criteria for response evaluation. The new criteria
      included important changes such as unidimensional tumour measurement, selection
      of target lesions with a minimum size, details concerning imaging modalities and
      a new threshold for assignment of objective progression. RECIST was published in
      February 2000 and very quickly came into operation first in clinical trials
      performed under the auspices of EORTC, US NCI or NCI Canada Clinical Trials Group
      but was adopted quickly thereafter by the entire cancer clinical research
      community. As several key features of RECIST were based on analysis of
      retrospective clinical data, it was felt important to carefully monitor the
      implementation of the guidelines and stimulate prospective validation studies.
      This paper reviews the literature that has been published on RECIST from 2000 up
      to November 2005. In total 60 papers and ASCO, abstracts directly refer to
      research studies or reviews related to RECIST and its implementation. Amongst the
      60 references identified for this review, 11 papers refer to validation studies
      (seven prospective and four retrospective), six papers refer to the comparison of
      unidimensional measurements versus bi or tri-dimensional measurements, 12 papers
      address issues raised with the implementation of RECIST in Mesothelioma and
      Gastro-Intestinal Stromal Tumours and four papers report on an adaptation of
      RECIST for specific tumour types. In general, RECIST has been well received by
      the scientific community and most validation studies fully support the
      implementation of the new criteria. As expected, however, some issues have been
      identified. In keeping with the mathematical differences in definition of
      progression, RECIST delays the identification of progression as compared to WHO
      criteria in some instances. RECIST criteria are not easily applicable in some
      types of trials such as those in paediatric tumours and in mesothelioma.
      Furthermore, anatomical changes in the tumour as described by RECIST may be
      detected later than functional changes in some circumstances, as for example in
      Gastro-Intestinal Stromal Tumours treated with Imatinib. However, there is no
      other universal method of tumour assessment as yet and functional imaging methods
      have not been validated and will not be widely available for some time. The
      findings of this review, together with experience acquired thus far and the
      results of some ongoing research projects, have paved the way for RECIST 2.0 to
      be hopefully announced later this year.

PMID- 16616488
TI  - Synthesis, hydrolyses and dermal delivery of N-alkyl-N
      alkyloxycarbonylaminomethyl (NANAOCAM) derivatives of phenol, imide and thiol
      containing drugs.
AB  - Synthesis, characterization and hydrolysis in aqueous buffers of novel N-alkyl-N
      alkyloxycarbonylaminomethyl (NANAOCAM) derivatives of substituted phenols,
      theophylline (Th) and 6-mercaptopurine (6MP) were carried out. The mechanism of
      hydrolysis was further investigated by synthesis, characterization and hydrolysis
      of N-aryl-N-alkyloxycarbonylaminomethyl (NArNAOCAM) derivatives of phenols. The
      hydrolysis follows pseudounimolecular first order kinetics and operates by way of
      an S(N)1-type mechanism. Topical delivery of selected derivatives of
      acetaminophen (APAP), Th and 6MP was examined in in vitro diffusion cell
      experiments from IPM across hairless mice skins. The prodrug of APAP and 6MP
      increased permeation across the skin by about 2- and 4-fold, respectively,
      compared to the parent drug. NANAOCAM promoieties can act as novel prodrug
      derivatives of phenol, imide and thiol containing drugs for enhancing topical
      absorption.

PMID- 16616489
TI  - Suzuki-type Pd(0) coupling reactions in the synthesis of 2-arylpurines as Cdk
      inhibitors.
AB  - A new series of 2-aryl-substituted purine derivatives has been synthesized by
      Suzuki Pd(0) coupling reactions. Moderate in vitro inhibitory activity against
      Cdk1 and Cdk5 was observed. These compounds are inactive against GSK3.

PMID- 16616490
TI  - Carboxy derivatized glucosamine is a potent inhibitor of matrix metalloproteinase
      9 in HT1080 cells.
AB  - Experimental evidences have confirmed that matrix metalloproteinases (MMPs) play
      a fundamental role in a wide variety of pathologic conditions and recent advances
      in medicinal chemistry approach to the design of MMP inhibitors with desired
      structural and functional properties. Among MMPs, MMP-9 has demonstrated to play
      a major role in the establishment of metastases and it is substantially increased
      in the majority of malignant tumors. Inhibition of MMP-9 is thought to have a
      therapeutic benefit to cancer. Results of this study present a novel synthetic
      MMP-9 inhibitor that downregulates MMP-9 expression level in HT1080, human
      fibrosarcoma cells.

PMID- 16616491
TI  - RNA interference by 2',5'-linked nucleic acid duplexes in mammalian cells.
AB  - Synthetic small interfering RNA (siRNA) mediated silencing of a specific gene is
      emerging as a powerful tool for gene regulation. However, their utility is
      limited for therapeutic applications primarily due to poor stability. The 2',5'
      linked oligonucleotides are known to be more stable to nucleolytic degradation
      than 3',5'-linked oligonucleotides. The 2',5'-linkage is tolerated in the sense
      strand of the siRNA duplex. However, the 2',5'-linkage is not tolerated in the
      antisense strand of the siRNA duplex.

PMID- 16616492
TI  - A practical synthesis of the major 3-hydroxy-2-pyrrolidinone metabolite of a
      potent CDK2/cyclin A inhibitor.
AB  - The synthesis of the major metabolite of a potent 3-aminopyrazole CDK2/cyclin A
      inhibitor is presented. A stereoconservative approach starting from malic acid
      was employed to construct the hydroxy-substituted pyrrolidinone moiety. In the
      key step of the synthesis the use of cyanoborohydride immobilized on Amberlyst 26
      in trifluoroethanol represented a valid alternative to conventional solution
      phase reducing agents.

PMID- 16616493
TI  - Benzo[b]thiophene-2-carboxamides and benzo[b]furan-2-carboxamides are potent
      antagonists of the human H3-receptor.
AB  - Benzo[b]thiophene-2-carboxamides and benzo[b]furan-2-carboxamides have been found
      to be antagonists on the human histamine-3-receptor, showing a Ki value of as low
      as 4 nM.

PMID- 16616494
TI  - Racemic and chiral sulfoxides as potential prodrugs of the COX-2 inhibitors Vioxx
      and Arcoxia.
AB  - The preparation of the sulfoxide analogues 2 and 4, and their enantiomeric pure
      forms is discussed as well as their potential to act as prodrugs to the potent
      and selective sulfone-containing COX-2 inhibitors rofecoxib and etoricoxib.
      Sulfoxides 2 and 4 were shown to be effectively transformed in vivo into
      rofecoxib and etoricoxib, respectively, after oral administration in rats. In the
      case of sulfoxide 2, both a slightly improved pharmacokinetic profile and a
      better pharmacological activity in an arthritis model were seen when compared
      with rofecoxib.

PMID- 16616495
TI  - Novel alkylpolyaminoguanidines and alkylpolyaminobiguanides with potent
      antitrypanosomal activity.
AB  - A series of polyaminoguanidines and polyaminobiguanides were synthesized and
      evaluated as potential antitrypanosomal agents. These analogues inhibit
      trypanothione reductase (TR) with IC50 values as low as 0.95 microM, but do not
      inhibit the closely related human enzyme glutathione reductase (GR). The most
      effective analogues, 7a, 7b and 8d, inhibited parasitic growth in vitro with IC50
      values of 0.18, 0.09 and 0.18 microM, respectively. These agents represent a
      promising new class of potential antitrypanosomal agents.

PMID- 16616496
TI  - A/T-targeted somatic hypermutation: critique of the mainstream model.
AB  - The "affinity maturation" of the humoral immune response is driven by antigen
      activated somatic hypermutation (SHM) of the genes that encode antibody variable
      regions and the subsequent antigenic selection of mutant clones. The molecular
      mechanism of SHM is yet to be completely elucidated. SHM affects cytosine-guanine
      (C/G) and adenine-thymine (A/T) pairs with approximately equal frequency in vivo.
      The proposition that error-prone DNA-dependent DNA synthesis explains A/T
      targeted hypermutagenesis seems to have mainstream support within the
      hypermutation research community at present. A major feature of SHM in vivo is
      that C/G hypermutation is strand unbiased, whereas A/T hypermutation is strand
      biased. We show that the "DNA-based polymerase error" model of A/T-targeted
      hypermutagenesis does not explain this important aspect of SHM.

PMID- 16616497
TI  - Translocation of mitochondrial inner-membrane proteins: conformation matters.
AB  - Most of the mitochondrial inner-membrane proteins are generated without a
      presequence and their targeting depends on inadequately defined internal
      segments. Despite the numerous components of the import machinery identified by
      proteomics, the properties of hydrophobic import substrates remain poorly
      understood. Recent studies support several principles for these membrane
      proteins: first, they become organized into partially assembled forms within the
      translocon; second, they present noncontiguous targeting signals; and third, they
      induce conformational changes in translocase subunits, thereby mediating
      "assembly on demand" of the import machinery. It is possible that the energy
      needed for these proteins to pass across the outer membrane, to travel through
      the intermembrane space and to target the inner-membrane surface is provided by
      conformational changes involving import components that seem to have natively
      unfolded structures. Such structural malleability might render some of the
      translocase subunits more adept at driving the protein import process.

PMID- 16616498
TI  - Systems analyses characterize integrated functions of biochemical networks.
AB  - Metabolic, regulatory and signaling pathways have been characterized in detail
      over the past century. As the amount of genomic, proteomic and metabolic data has
      increased, and the mathematical and analytical capabilities of interrogating
      these data have advanced, the overlapping roles of pathway constituents have been
      described. These developments reflect the truly integrated nature of subcellular
      biochemical networks. Systems analyses, including the reconstruction of
      stoichiometric networks, provide a key set of tools for quantifying overlap among
      the metabolic, regulatory and signaling functions of network components.
      Accounting for this integration is crucial for accurately describing the function
      of biochemical networks.

PMID- 16616499
TI  - Synthesis of new class dipeptide analogues with improved permeability and
      antithrombotic activity.
AB  - 3-(S)-1,2,3,4-Tetrahydro-beta-carboline-3-carboxylic acid isolated from A.
      Chinese G. Don was found to possess moderate anti-aggregation activity, but with
      poor bioavailability. To improve its pharmacological property, we designed and
      synthesized a series of novel dipeptide analogues by incorporating tetrahydro
      beta-carboline-3-carboxylic acid skeleton as an amino acid surrogate (*Trp). It
      turned out these dipeptide analogues exhibited good membrane permeability based
      on in vitro Caco-2 cell monolayers permeability assay. As a result, the overall
      biological properties of these molecules were significantly improved depending on
      the nature of the amino acid residues introduced onto the 3-position of the
      tetrahydro-beta-carboline moiety. It was very interesting to notice that these
      dipeptide analogues (5b,c,h,i,n,o,p,q) displayed a remarkable dual
      antiaggregatory activity in both of ADP- and PAF-induced platelet aggregation
      assay, and their aggregation response was significantly higher than that of
      aspirin (p<0.01). In addition, these dipeptide analogues were observed for the
      dose-dependent antithrombotic effect using in vivo rat arterial thrombosis model.
      The potency of antithrombotic activity of 5h,i,n,p was significantly higher than
      that of aspirin (n=12, p<0.01) at equal dose (5 micromol/kg).

PMID- 16616500
TI  - Asymmetric reduction of 3-aryl-3-keto esters using Rhizopus species.
AB  - Ethyl 3-aryl-3-oxopropanoates (aryl: phenyl, 2-fluorophenyl, 3-nitrophenyl, and 4
      nitrophenyl) were reduced enantioselectively to the corresponding (S)-alcohols by
      the fungus Rhizopus arrhizus and other Rhizopus sp. The best results were
      generally obtained with Rhizopus arrhizus (wild type) and Rhizopus nivius NCIM
      958 with 6h incubation. A longer incubation period led to ester hydrolysis
      followed by decarboxylation and microbial reduction for all the substrates
      especially the 3-nitrophenyl ester.

PMID- 16616501
TI  - Discovery, structure-activity relationship study, and oral analgesic efficacy of
      cyproheptadine derivatives possessing N-type calcium channel inhibitory activity.
AB  - Antiallergic drug cyproheptadine (Cyp) is known to have inhibitory activities for
      L-type calcium channels in addition to histamine and serotonin receptors. Since
      we found that Cyp had an inhibitory activity against N-type calcium channel, Cyp
      was optimized to obtain more selective N-type calcium channel blocker with
      analgesic action. As a consequence of the optimization, we found 13 with potent N
      type calcium channel inhibitory activity which had lower inhibitory activities
      against L-type calcium channel, histamine (H1), and serotonin (5-HT2A) receptors
      than those of Cyp. 13 showed an oral analgesic activity in rat formalin-induced
      pain model.

PMID- 16616502
TI  - Synthesis, reactions and structure-activity relationships of 1
      hydroxyspiro[2.5]cyclooct-4-en-3-ones: illudin analogs with in vitro cytotoxic
      activity.
AB  - 1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones-analogs of natural illudines--were
      prepared in good yields by cyclization of 1,3-dicarbonyl dianions or 1,3-bis
      silyl enol ethers ('masked dianions') with 1,1-diacylcyclopropanes. Several
      spirocyclopropanes showed a significant antiproliferative activity against human
      leukemia HL60 cells in vitro. 1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones represent
      highly reactive precursors of unstable spiro[5.2]cycloocta-4,7-dien-6-ones and
      reactions with a number of nucleophiles were studied.

PMID- 16616503
TI  - Novel potent and selective calcium-release-activated calcium (CRAC) channel
      inhibitors. Part 2: Synthesis and inhibitory activity of aryl-3
      trifluoromethylpyrazoles.
AB  - To identify potent and selective calcium-release-activated calcium (CRAC) channel
      inhibitors, we examined the structure-activity relationships of the pyrazole and
      thiophene moieties in compound 4. Compound 25b was found to exhibit highly potent
      and selective inhibitory activity for CRAC channels and further modifications of
      the pyrazole and benzoyl moieties of compound 25b produced compound 29. These
      compounds were potent inhibitors of IL-2 production in vitro and also acted as
      inhibitors in pharmacological models of diseases resulting from T-lymphocyte
      activation, after oral administration.

PMID- 16616504
TI  - Benzofuro[3,2-f][1]benzopyrans: a new class of antitubercular agents.
AB  - Alkylation of 2-hydroxydibenzofuran with 3-chloro-3-methyl-1-butyne, followed by
      Claisen rearrangement, gave access to 3,3-dimethyl-3Hbenzofuro[3,2-f][1]
      benzopyran. Several derivatives modified at the pyran 1,2-double bond were
      prepared, including the corresponding dihydro compound and (+/-)-cis-diol, which
      was converted into diacetate and cyclic carbonate upon acylation. Both 3,3
      dimethyl-3Hbenzofuro[3,2-f][1]benzopyran and 1,2-dihydro-3,3-dimethyl
      3Hbenzofuro[3,2-f][1]benzopyran displayed significant activities when tested
      against Mycobacterium tuberculosis H37Rv and Beijing strains, with MIC99 in the
      range of 1-10 microg/ml. Further biological studies demonstrated good activities
      against drug-resistant mycobacterial strains. These compounds appear as promising
      specific antitubercular agents, since they exhibited neither significant
      cytotoxicity against mammal cells, nor effect on the growth of various bacteria
      and fungi.

PMID- 16616505
TI  - Toward the control of Leptosphaeria maculans: design, syntheses, biological
      activity, and metabolism of potential detoxification inhibitors of the crucifer
      phytoalexin brassinin.
AB  - Brassinin (1), a crucial plant defense produced by crucifers, is detoxified by
      the phytopathogenic fungus Leptosphaeria maculans (Phoma lingam) to indole-3
      carboxaldehyde using a putative brassinin oxidase. Potential inhibitors of
      brassinin detoxification were designed by replacement of its dithiocarbamate
      group (toxophore) with carbamate, dithiocarbonate, urea, thiourea, sulfamide,
      sulfonamide, dithiocarbazate, amide, and ester functional groups. In addition,
      the indolyl moiety was substituted for naphthalenyl and phenyl. The syntheses and
      chemical characterization of these potential detoxification inhibitors, along
      with their antifungal and cytotoxic activity, as well as screening using cultures
      of L. maculans are reported. Overall, three types of interaction were observed in
      cultures of L. maculans co-incubated with the potential inhibitors and brassinin:
      (1) a decrease on the rate of brassinin detoxification due to the strong
      inhibitory activity of the compound on fungal growth, (2) a decrease on the rate
      of brassinin detoxification due to the inhibitory activity of the compound on the
      putative brassinin oxidase, and (3) a low to no detectable effect on the rate of
      brassinin detoxification. A noticeable decrease in the rate of brassinin
      detoxification was observed in the presence of N'-methylbrassinin, methyl N
      methyl-N-(naphthalen-2-ylmethyl) dithiocarbamate, tryptophol dithiocarbonate, and
      methyl 3-phenyldithiocarbazate. Tryptophol dithiocarbonate appeared to be the
      best inhibitor among the designed compounds, representing the first inhibitor of
      brassinin detoxification and potentially the first selective protecting agent of
      oilseed crucifers against L. maculans infestation.

PMID- 16616506
TI  - Crystallographic studies on N-azidoacetyl-beta-D-glucopyranosylamine, an
      inhibitor of glycogen phosphorylase: comparison with N-acetyl-beta-D
      glucopyranosylamine.
AB  - N-acetyl-beta-D-glucopyranosylamine (NAG) is a potent inhibitor (Ki=32 microM) of
      glycogen phosphorylase b (GPb), and has been employed as a lead compound for the
      structure-based design of new analogues, in an effort to utilize its potential as
      a hypoglycaemic agent. Replacement of the acetamido group by azidoacetamido group
      resulted in an inhibitor, N-azidoacetyl-beta-D-glucopyranosylamine (azido-NAG),
      with a Ki value of 48.7 microM, in the direction of glycogen synthesis. In order
      to elucidate the mechanism of inhibition, we determined the ligand structure in
      complex with GPb at 2.03 A resolution, and the structure of the fully acetylated
      derivative in the free form. The molecular packing of the latter is stabilized by
      a number of bifurcated hydrogen bonds of which the one involving a bifurcated C
      H...N...H-C type hydrogen bonding is rather unique in organic azides. Azido-NAG
      can be accommodated in the catalytic site of T-state GPb at approximately the
      same position as that of NAG and stabilizes the T-state conformation of the 280 s
      loop by making several favourable contacts to residues of this loop. The
      difference observed in the Ki values of the two analogues can be interpreted in
      terms of desolvation effects, subtle structural changes of protein residues and
      changes in water structure.

PMID- 16616507
TI  - Determination of hERG channel blockers using a decision tree.
AB  - A decision tree approach for the in silico prediction of Torsade de Pointes (TdP)
      causing drugs is presented. As TdP is frequently associated with QT-interval
      prolongation due to inhibition of the rapid activating delayed rectifier
      potassium channel in the heart (hERG channel), the properties of such blockers
      were investigated by molecular modeling and semi-empirical AM1 molecular orbital
      calculations. In addition, we derived a pharmacophoric SMARTS string using
      structural information from high affinity compounds. A corresponding search in
      the PubChem database identified several compounds that exhibit QT-interval
      prolonging activity that were not among our data set. This SMARTS string
      furthermore showed to be the most significant descriptor in the decision tree
      approach from which guidelines for the design of safe compounds are suggested.

PMID- 16616508
TI  - Chemoenzymatic synthesis of both enantiomers of alpha-tocotrienol.
AB  - The stereoselective acylation of the achiral chromanedimethanol derivative 1 by
      vinyl acetate in the presence of Candida antarctica lipase B gave the (S)
      monoester 2 in high enantiomeric purity (ee > or = 98%). Enzymatic hydrolysis of
      diesters of compound 1 failed to give (R)-monoester 2 in good yield and high ee.
      Thus, both enantiomers of alpha-tocotrienol were synthesized from the (S)
      monoester 2.

PMID- 16616509
TI  - Test of internal-conversion theory with precise gamma- and X-ray spectroscopy.
AB  - Precise measurements of K-shell internal conversion coefficients (ICCs) are being
      used to determine the best method for calculating these coefficients. A recent
      result for the M4 transition from 193Irm has been refined, demonstrating
      conclusively that the atomic vacancy created by the ejected electron must be
      properly accounted for in the calculation of ICCs. Measurements of additional
      cases are discussed.

PMID- 16616510
TI  - An intuitive visualisation of intercomparison results applied to the KCDB.
AB  - A simple and intuitive graphical method is presented for producing a summary
      overview of experimental results of a common measurand, e.g. in the frame of an
      intercomparison. The PomPlots display (relative) deviations of individual results
      from the consensus value on the horizontal axis and (relative) uncertainties on
      the vertical axis. The z-scores, z=1, 2 and 3, are represented by diagonal lines,
      creating the aspect of a pyramidal structure. The most accurate and precise
      measurement results should be situated close to the top of the pyramid. The plots
      are used to visualise data from the BIPM key comparison database on primary
      radioactivity measurements.

PMID- 16616511
TI  - Potentials and pitfalls of clinical outcome research studies in cardiac surgery.

PMID- 16616514
TI  - SOCS proteins and caveolin-1 as negative regulators of endocrine signaling.
AB  - Recently, a new class of regulatory molecules has emerged; these molecules,
      termed SOCS proteins, function as suppressors of cytokine signaling. SOCS
      proteins negatively regulate the Janus kinase signal transducer and activator of
      transcription (JAK-STAT) signaling cascade. Interestingly, it appears that other
      proteins, such as caveolin-1, can also function as suppressors of cytokine
      signaling by inhibiting the kinase activity of JAK family members. This might
      result from the ability of caveolin-1 to function as a broad-spectrum kinase
      inhibitor through the caveolin-scaffolding domain.

PMID- 16616515
TI  - TNF receptor deficiency reveals a translational control mechanism for adriamycin
      induced Fas expression in cardiac tissues.
AB  - Adriamycin, ADR, a potent chemotherapeutic agent, has been demonstrated to cause
      cardiomyocyte apoptosis, in part, via the Fas/Fas ligand-mediated cell death
      pathway. Our previous studies suggested that TNF-alpha receptors may mediate
      cardioprotection against ADR toxicity by the suppression of the Fas-mediated
      pathway. However, the role of TNF-alpha receptors in this process is unclear. In
      the present study, we extended our initial observation to determine the molecular
      mechanisms by which ADR induced Fas expression in the presence and absence of TNF
      receptors. Our results demonstrated that ADR-mediated p53 and AP-1 interaction
      and increased Fas mRNA levels independent of TNF receptors. However, the levels
      of Fas proteins only increased in the cardiac tissues of TNF receptor-deficient
      mice. These results demonstrated that the suppression of ADR-induced Fas
      expression by TNF receptors was not regulated at transcriptional levels, but may
      be regulated at a translational level.

PMID- 16616516
TI  - A dynamic model for action understanding and goal-directed imitation.
AB  - The understanding of other individuals' actions is a fundamental cognitive skill
      for all species living in social groups. Recent neurophysiological evidence
      suggests that an observer may achieve the understanding by mapping visual
      information onto his own motor repertoire to reproduce the action effect.
      However, due to differences in embodiment, environmental constraints or motor
      skills, this mapping very often cannot be direct. In this paper, we present a
      dynamic network model which represents in its layers the functionality of neurons
      in different interconnected brain areas known to be involved in action
      observation/execution tasks. The model aims at substantiating the idea that
      action understanding is a continuous process which combines sensory evidence,
      prior task knowledge and a goal-directed matching of action observation and
      action execution. The model is tested in variations of an imitation task in which
      an observer with dissimilar embodiment tries to reproduce the perceived or
      inferred end-state of a grasping-placing sequence. We also propose and test a
      biologically plausible learning scheme which allows establishing during practice
      a goal-directed organization of the distributed network. The modeling results are
      discussed with respect to recent experimental findings in action
      observation/execution studies.

PMID- 16616517
TI  - Nonpersistent pesticide exposure self-report versus biomonitoring in farm
      pesticide applicators.
AB  - PURPOSE: Few studies using biologic markers to examine nonpersistent pesticide
      exposure among pesticide applicators were conducted in field settings. This study
      compares self-reported dermal, inhalation, and ingestion exposures with
      urinalysis results after one-time application of the commonly used herbicide
      atrazine to field crops. It was hypothesized that: i) applicator reports of
      exposure would be associated positively with detection of urinary atrazine
      metabolites, and ii) applicator reports of personal-protective-equipment (PPE)
      use would be associated negatively with detection of urinary atrazine
      metabolites. METHODS: Wisconsin dairy farmers were randomly selected to
      participate in 1997 to 1998 and were instructed to collect a urine sample 8 hours
      after the first pesticide application of the season. Farmers then were
      interviewed within 1 week of their first application to report on application
      practices. Eighty-six urine samples were analyzed for deethylatrazine, a major
      atrazine metabolite. RESULTS: Comparing urinalysis results with self-reported
      dermal, inhalation, and ingestion exposure showed poor agreement between self
      reported exposure and urinary deethylatrazine detections (all kappa < 0.40).
      Multivariate linear regression modeling with deethylatrazine level as the outcome
      showed that self-reported practices did not significantly predict atrazine
      metabolite levels. CONCLUSIONS: Possible explanations for the discrepancies
      between urinalysis results and self-reported data include: i) inaccuracies in
      self-reported data and ii) substantial interpersonal variation in atrazine
      metabolism, resulting in major differences in body burden for similar exposures.
      Either explanation poses challenges for epidemiologic studies of the health
      effects of pesticides, which rely solely on self-reported measures of exposure.
      Additional evaluation of determinants of accuracy in self-assessed occupational
      and environmental exposures is needed.

PMID- 16616518
TI  - How specific MHC class I and class II combinations affect disease resistance
      against infectious salmon anaemia in Atlantic salmon (Salmo salar).
AB  - The aim was to evaluate the performance of selected individual MHC class I and
      class II alpha (A) alleles, and combinations of these on disease resistance
      against infectious salmon anaemia (ISA). The material consisting of 1966 fish
      from seven families, contained five MHC class I alleles and four MHC class II A
      alleles. Which representing given class II A and class II beta (B) haplotypes,
      totalling 19 MHC class I and class II A genotypes. The fish were challenged with
      infectious salmon anaemia virus (ISAV), the virus causing ISA. Dead fish were
      collected daily during the challenge experiment and the survivors were collected
      at termination. All fish were genotyped for MHC class I and class II A. The total
      mortality in the material was 85.14%. For MHC class I, UBA*0201 and UBA*0301 were
      significantly the most resistant alleles, while UBA*0601 for class I and DAA*0301
      for class II A were the significantly most susceptible alleles. The analysis of
      combined MHC class I and class II A genotypes detected that fish with the
      genotype UBA*0201/*0301;DAA*0201/*0201 were the most resistant fish with a hazard
      ratio (HR) at 0.750, while the fish with the genotypes
      UBA*0601/*0801;DAA*0501/*0501 and UBA*0201/*0301;DAA*0301/*0501 were the most
      susceptible fish with HR of 1.334 and 1.425. In addition, Cox regression analysis
      within family detected combined MHC class I and class II A genotypes that
      contributed significantly to resistance and susceptibility. The study confirmed
      the expectation of performance of individual MHC class I and class II A alleles,
      and also detected an effect of MHC class I and class II A in combinations.

PMID- 16616519
TI  - Lower median nerve block impairs precision grip.
AB  - The purpose of this study was to investigate precision grip impairment caused by
      a lower median nerve block at the wrist. The median nerve block was achieved by
      injecting bupivacaine hydrochloride into the carpal tunnel, which acutely
      simulated a median neuropathy. Seven healthy male subjects were instructed to
      grip, lift, and hold an instrumented handle within 60s using precision grip. The
      same tasks were performed before and after the nerve block. Force and torque data
      were recorded using two miniature 6-component force/torque transducers. The
      precision grip was quantified by the safety margin (i.e. the difference between
      the actual grip force and the minimal grip force to keep the object from
      dropping), the variation of grip force, and the migration area of center of
      pressure (i.e. the area defined by the center of pressure at a digit-transducer
      surface while holding the handle). Two subjects were unable to complete the
      precision grip tasks after the nerve block, and their data were excluded from the
      analyses. The median nerve block caused significant increases (P<0.05) in the
      safety margin of the grip force (>50%), the grip force variation (>80%), and the
      area of center of pressure migration (>250%). Median nerve block at the wrist
      impairs the fine motor control during precision grip. Our results corroborate the
      important role played by sensory function in hand fine motor control. Clinically,
      the measures related to precision grip have the potential to quantify impairment
      of hand function caused by neuromuscular disorders, to monitor the progress of a
      hand disorder, and to evaluate the efficacy of a treatment or rehabilitation
      procedure.

PMID- 16616520
TI  - Neural substrates for dividing and focusing attention between simultaneous
      auditory and visual events.
AB  - With information constantly bombarding the human sensory systems, how is it that
      we attend to behaviorally relevant information? The present study examined the
      behavioral and neural bases of attending to one sense while ignoring another
      sense (bimodal selective attention) contrasted with attending simultaneously to
      two senses (bimodal divided attention). In a functional magnetic resonance
      imaging (fMRI) study, subjects simultaneously heard novel melodies and viewed
      geometric shapes. They were instructed to actively attend to only one or to both
      senses (selective or divided attention) or as a baseline condition, passively
      observe both (bimodal passive). Memory tests for both attended and unattended
      stimuli validated that subjects were following the attention instructions.
      Selective attention led to increased activity in relevant sensory cortices while
      simultaneously leading to decreased activity in irrelevant sensory cortices. The
      divided attention instruction did not lead to a global increase in sensory cortex
      activity compared to the bimodal passive baseline condition. However, divided
      attention did recruit heteromodal areas in the left dorsolateral prefrontal
      cortex, while selective attention did not recruit any frontal areas. We propose
      that sustained selective and divided bimodal attention were achieved via distinct
      neural processes. Selective attention was achieved primarily via modulation of
      the sensory cortices. Divided attention was achieved for most individuals via
      recruitment of the middle-dorsolateral prefrontal cortex. However, there was also
      a trade-off between activity in posterior-dorsolateral prefrontal cortex and
      sensory regions, such that individuals who demonstrated the best performance
      during divided attention also showed the greatest recruitment of sensory
      cortices.

PMID- 16616521
TI  - Structure and evolution of the mitochondrial control region in oryx.

PMID- 16616522
TI  - Specific phospholipid recognition by human immunodeficiency virus type-1
      neutralizing anti-gp41 2F5 antibody.
AB  - HIV-1 neutralizing monoclonal antibody (Mab) 2F5 recognizes a membrane
      partitioning gp41 sequence. Just recently its capacity to react with cardiolipin
      has been demonstrated. Here, we have studied the specificity of Mab2F5
      phospholipid interactions comparing partitioning into lipid bilayers with
      recognition of molecular species dispersed in solution. Using a liposome-based
      ELISA we demonstrate a preferential association with cardiolipin bilayers. When
      different soluble lysoderivatives were compared in their capacity to inhibit
      Mab2F5 binding to immobilized HIV-1 peptide epitope, only dilysocardiolipin
      resulted effective in blocking the process. Dilyso-cardiolipin also competed with
      native-functional gp41 for 2F5 recognition. Thus, our data support specific
      cardiolipin recognition by 2F5 that is not dependent on lipid bilayer assembly
      and involves the epitope-binding site. These findings might be of relevance for
      understanding the molecular basis of HIV-1 immune evasion.

PMID- 16616523
TI  - Pharmacologic transglutaminase inhibition attenuates drug-primed liver
      hypertrophy but not Mallory body formation.
AB  - Mallory bodies (MBs) are characteristic of several liver disorders, and consist
      primarily of keratins with transglutaminase-generated keratin crosslinks. We
      tested the effect of the transglutaminase-2 (TG2) inhibitor KCC009 on MB
      formation in a mouse model fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC).
      KCC009 decreased DDC-induced liver enlargement without affecting MB formation or
      extent of liver injury. TG2 protein and activity increased after DDC feeding and
      localized within and outside hepatocytes. KCC009 inhibited DDC-induced
      hepatomegaly by affecting hepatocyte cell size rather than proliferation. Hence,
      TG2 is a potential mediator of injury-induced hepatomegaly via modulation of
      hepatocyte hypertrophy, and KCC009-mediated TG2 inhibition does not affect mouse
      MB formation.

PMID- 16616524
TI  - Identification of the gene encoding hydroxyacid-oxoacid transhydrogenase, an
      enzyme that metabolizes 4-hydroxybutyrate.
AB  - To identify the sequence of hydroxyacid-oxoacid transhydrogenase (HOT),
      responsible for the oxidation of 4-hydroxybutyrate in mammalian tissues, we have
      purified this enzyme from rat liver and obtained partial sequences of proteins
      coeluting with the enzymatic activity in the last purification step. One of the
      identified proteins was 'iron-dependent alcohol dehydrogenase', an enzyme encoded
      by a gene present on human chromosome 8q 13.1 and distantly related to bacterial
      4-hydroxybutyrate dehydrogenases. The identification of this protein as HOT was
      confirmed by showing that overexpression of the mouse homologue in HEK cells
      resulted in the appearance of an enzyme catalyzing the alpha-ketoglutarate
      dependent oxidation of 4-hydroxybutyrate to succinate semialdehyde.

PMID- 16616525
TI  - Cytoplasmic Listeria monocytogenes stimulates IFN-beta synthesis without
      requiring the adapter protein MAVS.
AB  - The mitochondria-associated adapter protein MAVS (also called IPS-1, VISA or
      CARDIF, designated MAVS for reasons of simplicity in our manuscript) relays
      signals from cytoplasmic sensors of viral RNA to the IRF3 kinase complex and the
      interferon-beta (IFN-beta) gene. Using siRNA-mediated knock-down in macrophages
      we show that IFN-beta synthesis in response to transfected, intracellular double
      stranded RNA (dsRNA), a pathogen-associated molecular pattern of viruses, is
      decreased in absence of MAVS. By contrast, the Gram-positive bacterium Listeria
      monocytogenes targets the IFN-beta gene without detectable MAVS requirement. The
      data show that MAVS is not a central adapter protein for all cytoplasmic pathogen
      sensors that stimulate IFN-beta synthesis.

PMID- 16616526
TI  - Expression of pannexin family of proteins in the retina.
AB  - Expression of the Panx1 and Panx2 members of the pannexin family of gap junction
      proteins was studied in the retina by in situ hybridization and qRT-PCR. Both
      pannexins showed robust expression across the retina with predominant
      accumulation in the retinal ganglion cells (RGCs). In concordance,
      immunohistochemical analysis showed accumulation of the Panx1 protein in RGCs,
      amacrine, horizontal cells and their processes. Two Panx1 isoforms were detected:
      a ubiquitously expressed 58 kDa protein, and a 43 kDa isoform that specifically
      accumulated in the retina and brain. Our results indicated that Panx1 and Panx2
      are abundantly expressed in the retina, and may therefore contribute to the
      electrical and metabolic coupling, or to signaling between retinal neurons via
      the secondary messengers.

PMID- 16616527
TI  - Wistar rats with high versus low rearing activity differ in radial maze
      performance.
AB  - Substantial work has shown that rats although identical in stock, sex, age, and
      housing conditions can differ considerably in terms of behavior and physiology.
      Such individual differences, which can be detected by specific behavioral
      screening tests, are rather stable, that is, they probably reflect a behavioral
      disposition or trait. Here, we asked whether and how such differences might
      affect performance in a task of spatial learning and memory, the radial maze. As
      in our previous work, we used the degree of rearing activity in a novel open
      field to assign male adult outbred Wistar rats into those with high versus low
      rearing activity (HRA/LRA rats). They were then tested in a plus-maze for
      possible differences in anxiety-related behavior. Finally, and most importantly,
      they were food deprived and underwent maze training using an 8-arm radial maze
      with four non-baited and four baited arms. One of these arms consistently
      contained a larger bait size than the other three. In the open field, HRA rats
      not only showed more rearing behavior, but also more locomotor activity than LRA
      rats. In the plus-maze, HRA rats again showed more locomotion, but did not differ
      in open arm time or percentage of open arm entries, that is, conventional
      measures of anxiety-related behavior. In the radial maze, HRA rats consistently
      needed less time to consume all pellets than LRA rats, which was due to faster
      locomotion on the arms and less time spent at the food pits (especially in baited
      arms) of HRA rats. During the initial days of training, they were also more
      efficient in obtaining all food pellets available. Furthermore, HRA rats visited
      more arms and made relatively less reference memory errors than LRA rats. This
      allowed them to forage food quickly, but was paralleled by more working memory
      errors than in LRA rats. In general, working memory errors were more frequent in
      the arm with the large bait size, but there were no indications that HRA and LRA
      rats responded differently dependent on reward size. Finally, LRA rats lost
      slightly more weight than HRA rats during the period of food deprivation. These
      results are discussed with respect to the role of cognitive and motivational
      mechanisms, which as subject-inherent factors can contribute substantially to
      inter-individual variability in the radial maze.

PMID- 16616528
TI  - Visuospatial function in the beagle dog: an early marker of cognitive decline in
      a model of human aging and dementia.
AB  - Visuospatial learning and memory impairments are an early marker for age-related
      cognitive decline and Alzheimer's disease. Similar to humans, aged dogs show
      visuospatial learning and memory deficits (). One hundred and nine beagle dogs
      ranging between 0.25 and 11.99 years were tested on a visuospatial delayed non
      matching to position (DNMP) task to better characterize the progression of
      visuospatial deficits in the dog. Age predicted 48.2% of the variability in
      learning the DNMP, with dogs ranging from 1 to 11.99 years generally making more
      errors with increasing age. By contrast, puppies (<1 year) likely were showing
      developmental deficits, possibly due to an immature prefrontal cortex. Mild
      visuospatial deficits were detected by 6 years, which precedes the typical onset
      of amyloid-beta (Abeta) accumulation in the dog brain by two years, and can serve
      as an early marker for cognitive decline in the dog. These findings suggest that
      (1) age-related changes in visuospatial function in the dog models that seen in
      humans, further validating the dog as a model for human aging and dementia; and
      (2) other mechanisms, such as oxidative stress, soluble Abeta oligomers or
      cholinergic deficits, are likely contributing to the early impairment.

PMID- 16616529
TI  - Involvement of alpha-bungarotoxin-sensitive nicotinic receptors in long-term
      memory formation in the honeybee (Apis mellifera).
AB  - In the honeybee Apis mellifera, multiple-trial olfactory conditioning of the
      proboscis extension response specifically leads to long-term memory (LTM) which
      can be retrieved more than 24 h after learning. We studied the involvement of
      nicotinic acetylcholine receptors in the establishment of LTM by injecting the
      nicotinic antagonists mecamylamine (1 mM), alpha-bungarotoxin (alpha-BGT, 0.1 mM)
      or methyllycaconitine (MLA, 0.1 mM) into the brain through the median ocellus 20
      min before or 20 min after multiple-trial learning. The retention tests were
      performed 1, 3, and 24 h after learning. Pre-training injections of mecamylamine
      induced a lower performance during conditioning but had no effect on LTM
      formation. Post-training injections of mecamylamine did not affect honeybees'
      performances. Pre-training injections of MLA or post-training injection of alpha
      BGT specifically induced LTM impairment whereas acquisition as well as memory
      retrieval tested 1 or 3 h after learning was normal. This indicates that brain
      injections of alpha-BGT and MLA did not interfere with learning or medium-term
      memory. Rather, these blockers affect the LTM. To explain these results, we
      advance the hypothesis that honeybee alpha-BGT-sensitive acetylcholine receptors
      are also sensitive to MLA. These receptors could be essential for triggering
      intracellular mechanisms involved in LTM. By contrast, medium-term memory is not
      dependent upon these receptors but is affected by mecamylamine.

PMID- 16616530
TI  - Surgical approach to vascular complications of intravenous drug abuse.
AB  - OBJECTIVE: To assess the complications related to intravenous drug abuse. DESIGN:
      Prospective study. METHODS: Intravenous drug abusers (IVDAs) with vascular
      complications were assessed. RESULTS: Sixty-two patients presented with swelling
      and tenderness in the groin, and 3 patients with similar lesions in the cubital
      fossa. Infected pseudoaneurysms and deep vein thrombosis (DVTs) were diagnosed in
      41 and 31 patients respectively (27 patients had both lesions). In patients with
      infected pseudoaneurysms, 9 patients underwent excision with early
      revascularization and 32 patients underwent ligation without revascularization.
      For all patients with femoral vein thrombosis ligation and excision was
      performed. 4 patients with pure DVTs were managed conservatively. Disabling
      claudication occurred in 6 patients. Four of them underwent late
      revascularization with an acceptable outcome. CONCLUSIONS: Ligation without
      revascularization is the appropriate treatment of infected pseudoaneurysms in
      IVDAs. Late revascularization is of great importance in patients with disabling
      claudication after treatment of addiction. Pure septic DVTs can be managed
      conservatively.

PMID- 16616532
TI  - Thermal diffusivity and nuclear spin relaxation: a continuous wave free
      precession NMR study.
AB  - Continuous wave free precession (CWFP) nuclear magnetic resonance is capable of
      yielding quantitative and easily obtainable information concerning the kinetics
      of processes that change the relaxation rates of the nuclear spins through the
      action of some external agent. In the present application, heat flow from a
      natural rubber sample to a liquid nitrogen thermal bath caused a large
      temperature gradient leading to a non-equilibrium temperature distribution. The
      ensuing local changes in the relaxation rates could be monitored by the decay of
      the CWFP signals and, from the decays, it was possible to ascertain the
      prevalence of a diffusive process and to obtain an average value for the thermal
      diffusivity.

PMID- 16616531
TI  - Genotyping of Ureaplasma diversum isolates using pulsed-field electrophoresis.
AB  - Ureaplasma diversum has been associated with reproductive disorders in cattle and
      in the present study genotypic variations among U. diversum isolates obtained
      from the vaginal mucus of healthy cattle and sick animals were analyzed by
      enzymatic digestion and pulsed-field gel electrophoresis (PFGE). The influence of
      time and broth volume was important in obtaining sufficient cell sediment and DNA
      for PFGE. The method presented a high discriminatory power and satisfactory
      reproducibility for the analysis of detected variations among U. diversum
      isolates and strains. Different band profiles and wide genotypic heterogeneity
      were detected but no association between DNA polymorphism and sick or healthy
      animals could be established.

PMID- 16616533
TI  - Experimental validation of a T2rho transverse relaxation model using LASER and
      CPMG acquisitions.
AB  - The transverse relaxation rate (R2=1/T2) of many biological tissues are altered
      by endogenous magnetized particles (i.e., ferritin, deoxyhemoglobin), and may be
      sensitive to the pathological progression of neurodegenerative disorders
      associated with altered brain-iron stores. R2 measurements using Carr-Purcell
      Meiboom-Gill (CPMG) acquisitions are sensitive to the refocusing pulse interval
      (2taucp), and have been modeled as a chemical exchange (CE) process, while R2
      measurements using a localization by adiabatic selective refocusing (LASER)
      sequence have an additional relaxation rate contribution that has been modeled as
      a R2rho process. However, no direct comparison of the R2 measured using these two
      sequences has been described for a controlled phantom model of magnetized
      particles. The three main objectives of this study were: (1) to compare the
      accuracy of R2 relaxation rate predictions from the CE model with experimental
      data acquired using a conventional CPMG sequence, (2) to compare R2 estimates
      obtained using LASER and CPMG acquisitions, and (3) to determine whether the CE
      model, modified to account for R2rho relaxation, adequately describes the R2
      measured by LASER for a full range of taucp values. In all cases, our analysis
      was confined to spherical magnetic particles that satisfied the weak field
      regime. Three phantoms were produced that contained spherical magnetic particles
      (10 microm diameter polyamide powders) suspended in Gd-DTPA (1.0, 1.5, and 2.0
      mmol/L) doped gel. Mono-exponential R2 measurements were made at 4T as a function
      of refocusing pulse interval. CPMG measurements of R2 agreed with CE model
      predictions while significant differences in R2 estimates were observed between
      LASER and CPMG measurements for short taucp acquisitions. The discrepancy between
      R2 estimates is shown to be attributable to contrast enhancement in LASER due to
      T2rho relaxation.

PMID- 16616535
TI  - Homology modeling and molecular dynamics study of chorismate synthase from
      Shigella flexneri.
AB  - Shigellosis is a major public health problem in many developing countries.
      Antibiotic therapy can reduce the severity of the dysentery and prevent
      potentially lethal complication. However, owing to the increased resistance to
      most of the widely used and inexpensive antibiotics, there is an urgent need for
      new antibacterial agents, particularly those that act on novel targets.
      Chorismate synthase (CS) is a key enzyme in the shikimic acid pathway, which is
      essential for the synthesis of aromatic amino acids in bacteria. As an anti
      bacterial drug target, CS has been well validated. A homology model of Shigella
      CS with the flavin mononucleotide (FMN) binding was constructed using the crystal
      structure of CS from other species. The substrate 5-enolpyruvylshikimate 3
      phosphate (EPSP) was subsequently docked into the active site based on previous
      theoretical studies. Molecular dynamics (MD) was used to refine the starting
      ternary model. The model was well conserved during the 1.8 ns MD simulation with
      the equilibrium root mean square deviation (RMSD) value of 3.5 angstrom. The
      substrate binding energy was calculated and the electrostatic energy was found to
      be the most important term for binding. Decomposition of binding energies
      revealed that R129, R125, R327, R134 and R48 are important residues involved in
      substrate binding, which is useful for further site-directed mutagenesis
      experiments. In the absence of crystal structure, our study provides an early
      insight into the structure of CS from Shigella flexneri and its binding to the
      substrate and cofactor, thus facilitating the inhibitor design.

PMID- 16616536
TI  - The relationship among flow rate, chamber volume and calculated rate of
      metabolism in vertebrate respirometry.
AB  - A relationship exists among the calculated rate of metabolism of an animal
      enclosed in a chamber, chamber volume and air flow rate. A "critical" flow rate,
      defined as the minimal flow rate that produces a complete mixture of chamber
      gases, characterizes each chamber/animal combination. At flow rates below the
      critical flow rate, calculated rates of metabolism decrease with flow rate and
      approach zero as flow rate approaches zero. These calculated rates are unreliable
      estimates of rate of metabolism. At flow rates greater than the critical flow
      rate, calculated rates of metabolism are independent of flow rate because a
      reciprocal relationship exists between flow rate and the differential in oxygen
      content found between the air entering and exiting the chamber; they represent an
      accurate estimate of the animal's rate of metabolism under the conditions to
      which the animal is exposed. The critical flow rate increases with chamber
      volume, the animal's rate of metabolism and with any factor that increases rate
      of metabolism, including body mass, activity and in endotherms ambient
      temperatures below thermoneutrality, although chamber volume is its single most
      important determinant. Some evasions of the critical flow rate are discussed.

PMID- 16616537
TI  - The effects of hypoxia and pH on phenoloxidase activity in the Atlantic blue
      crab, Callinectes sapidus.
AB  - In its natural coastal and estuarine environments, the blue crab, Callinectes
      sapidus, often encounters hypoxia, accompanied by hypercapnia (increased CO2) and
      an associated decrease in water pH. Previous studies have shown that exposure to
      hypercapnic hypoxia (HH) impairs the crab's ability to remove culturable bacteria
      from its hemolymph. In the present study we demonstrate that the activity of
      phenoloxidase (PO), an enzyme critical to antibacterial immune defense in
      crustaceans, is decreased at the low levels of hemolymph O2 and pH that occur in
      the tissues of blue crabs exposed to HH. Hemocyte PO activity was measured at
      tissue O2 levels that occur in normoxic (5% and 15% O2, approximate venous and
      arterial hemolymph, respectively) and hypoxic (1% O2) crabs and compared to PO
      activity in air-saturated conditions (21% O2). PO activity decreased by 33%, 49%
      and 70% of activity in air at 15%, 5% and 1% O2, respectively. When O2 was held
      at 21% and pH lowered within physiological limits, PO activity decreased with pH,
      showing a 16% reduction at pH 7.0 as compared with a normoxic pH of 7.8. These
      results suggest that decreased PO activity at low tissue O2 and pH compromises
      the ability of crustaceans in HH to defend themselves against microbial
      pathogens.

PMID- 16616538
TI  - Hematological parameters in brood-rearing great tits in relation to habitat,
      multiple breeding and sex.
AB  - Very little is known about the causes and correlates for variation of individual
      condition in the wild. However, such knowledge is essential for understanding the
      mechanisms that mediate environmental effects to populations. We studied the
      variation of several hematological condition indices (hematocrit, albumin,
      globulin and triglyceride concentrations, albumin/globulin ratio, lymphocyte and
      heterophile concentrations and heterophile/lymphocyte ratio) and body mass in
      brood-rearing great tits (Parus major) in relation to habitat, multiple breeding
      and gender. Although great tits prefer deciduous forest to coniferous forests,
      individuals breeding in coniferous forests tended to be in a superior health
      state than those breeding in deciduous habitat. We suggest that this difference
      in adult condition can be caused by differences in breeding densities between
      habitats. Although there was some variation in condition indices between breeding
      attempts, none of these parameters measured at the end of the first breeding
      attempt predicted the probability of double breeding. We also found that females
      were in poorer condition and probably more stressed than males, both during the
      first and the second breeding attempt. These findings demonstrate that
      hematological parameters can be used to assess spatial and temporal variation of
      individual condition in the wild.

PMID- 16616539
TI  - The crisis in human resources for health.

PMID- 16616540
TI  - Not for sale at any price.

PMID- 16616541
TI  - HIV: compulsory testing and falling incidence?

PMID- 16616542
TI  - Antioxidant supplementation in pre-eclampsia.

PMID- 16616543
TI  - Has global HIV incidence peaked?

PMID- 16616544
TI  - BCG vaccination gets a boost.

PMID- 16616545
TI  - New look at the oxyhaemoglobin dissociation curve.

PMID- 16616546
TI  - Health inequalities and the UK Presidency of the EU.

PMID- 16616547
TI  - Cochrane and Campbell Collaborations, and health equity.

PMID- 16616548
TI  - Francisco Songane: champion of maternal and child health.

PMID- 16616549
TI  - Trial by media: dangers of misinterpretation of medical statistics.

PMID- 16616550
TI  - Fatal liver complications with flutamide.

PMID- 16616551
TI  - The FIELD study.

PMID- 16616552
TI  - The FIELD study.

PMID- 16616554
TI  - Epilepsy and stigma.

PMID- 16616555
TI  - Suicide in Japan.

PMID- 16616556
TI  - Compensation for vaccine injury in Hungary.

PMID- 16616557
TI  - Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial):
      randomised placebo-controlled trial.
AB  - BACKGROUND: Oxidative stress could play a part in pre-eclampsia, and there is
      some evidence to suggest that vitamin C and vitamin E supplements could reduce
      the risk of the disorder. Our aim was to investigate the potential benefit of
      these antioxidants in a cohort of women with a range of clinical risk factors.
      METHODS: We did a randomised, placebo-controlled trial to which we enrolled 2410
      women identified as at increased risk of pre-eclampsia from 25 hospitals. We
      assigned the women 1000 mg vitamin C and 400 IU vitamin E (RRR alpha tocopherol;
      n=1199) or matched placebo (n=1205) daily from the second trimester of pregnancy
      until delivery. Our primary endpoint was pre-eclampsia, and our main secondary
      endpoints were low birthweight (<2.5 kg) and small size for gestational age (<5th
      customised birthweight centile). Analyses were by intention to treat. This study
      is registered as an International Standard Randomised Controlled Trial, number
      ISRCTN 62368611 . FINDINGS: Of 2404 patients treated, we analysed 2395 (99.6%).
      The incidence of pre-eclampsia was similar in treatment placebo groups (15%
      [n=181] vs 16% [n=187], RR 0.97 [95% CI 0.80-1.17]). More low birthweight babies
      were born to women who took antioxidants than to controls (28% [n=387] vs 24%
      [n=335], 1.15 [1.02-1.30]), but small size for gestational age did not differ
      between groups (21% [n=294] vs 19% [n=259], 1.12 [0.96-1.31]). INTERPRETATION:
      Concomitant supplementation with vitamin C and vitamin E does not prevent pre
      eclampsia in women at risk, but does increase the rate of babies born with a low
      birthweight. As such, use of these high-dose antioxidants is not justified in
      pregnancy.

PMID- 16616558
TI  - Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in
      patients with acute cardiogenic pulmonary oedema: a meta-analysis.
AB  - BACKGROUND: Non-invasive positive pressure ventilation (NIPPV), using continuous
      positive airway pressure (CPAP) or bilevel ventilation, has been shown to reduce
      the need for invasive mechanical ventilation in patients with acute cardiogenic
      pulmonary oedema. We assessed additional benefits of NIPPV in a meta-analysis.
      METHODS: Meta-analysis comparison in acute cardiogenic pulmonary oedema was
      undertaken to compare (1) CPAP with standard therapy (oxygen by face-mask,
      diuretics, nitrates, and other supportive care), (2) bilevel ventilation with
      standard therapy, and (3) bilevel ventilation with CPAP, incorporating randomised
      controlled trials identified by electronic and hand search (1966-May, 2005). In
      23 trials that fulfilled inclusion criteria, we assessed the effect of NIPPV on
      hospital mortality and mechanical ventilation, estimated as relative risks.
      FINDINGS: CPAP was associated with a significantly lower mortality rate than
      standard therapy (relative risk 0.59, 95% CI 0.38-0.90, p=0.015). A non
      significant trend towards reduced mortality was seen in the comparison between
      bilevel ventilation and standard therapy (0.63, 0.37-1.10, p=0.11). We recorded
      no substantial difference in mortality risk between bilevel ventilation and CPAP
      (p=0.38). The need for mechanical ventilation was reduced with CPAP (0.44, 0.29
      0.66, p=0.0003) and with bilevel ventilation (0.50, 0.27-0.90, p=0.02), compared
      with standard therapy; but no significant difference was seen between CPAP and
      bilevel ventilation (p=0.86). Weak evidence of an increase in the incidence of
      new myocardial infarction with bilevel ventilation versus CPAP was recorded
      (1.49, 0.92-2.42, p=0.11). Heterogeneity of treatment effects was not evident for
      mortality or mechanical ventilation across patients' groups. INTERPRETATION: In
      patients with acute cardiogenic pulmonary oedema, CPAP and bilevel ventilation
      reduces the need for subsequent mechanical ventilation. Compared with standard
      therapy, CPAP reduces mortality; our results also suggest a trend towards reduced
      mortality after bilevel NIPPV.

PMID- 16616559
TI  - Trends in HIV-1 in young adults in south India from 2000 to 2004: a prevalence
      study.
AB  - BACKGROUND: Major increases in HIV-1 prevalence in India have been predicted.
      Incident infections need to be tracked to understand the epidemic's course,
      especially in some southern states of India where the epidemic is more advanced.
      To estimate incidence, we investigated the prevalence of HIV-1 in young people
      attending antenatal and sexually transmitted infection (STI) clinics in India.
      METHODS: We analysed unlinked, anonymous HIV-1 prevalence data from 294 050 women
      attending 216 antenatal clinics and 58 790 men attending 132 STI clinics in 2000
      04. Southern and northern states were analysed separately. FINDINGS: The age
      standardised HIV-1 prevalence in women aged 15-24 years in southern states fell
      from 1.7% to 1.1% in 2000-04 (relative reduction 35%; p(trend)<0.0001, yearly
      reduction 11%), but did not fall significantly in women aged 25-34 years.
      Reductions in women aged 15-24 years were seen in key demographic groups and were
      similar in sites tested continuously or in all sites. Prevalence in the north was
      about a fifth of that in the south, with no significant decreases (or increases)
      in 2000-04. Prevalence fell in men aged 20-29 years attending STI clinics in the
      south (p(trend)<0.0001), including those with ulcerative STIs (p(trend)=0.0008),
      but reductions were more modest in their northern counterparts. INTERPRETATION: A
      reduction of more than a third in HIV-1 prevalence in 2000-04 in young women in
      south India seems realistic, and is not easily attributable to bias or to
      mortality. This fall is probably due to rising condom use by men and female sex
      workers in south India, and thus reduced transmission to wives. Expansion of peer
      based condom and education programmes for sex workers remains a top priority to
      control HIV-1 in India.

PMID- 16616560
TI  - Effect of BCG vaccination on childhood tuberculous meningitis and miliary
      tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness.
AB  - BACKGROUND: BCG vaccine has shown consistently high efficacy against childhood
      tuberculous meningitis and miliary tuberculosis, but variable efficacy against
      adult pulmonary tuberculosis and other mycobacterial diseases. We assess and
      compare the costs and effects of BCG as an intervention against severe childhood
      tuberculosis in different regions of the world. METHODS: We calculated the number
      of tuberculous meningitis and miliary tuberculosis cases that have been and will
      be prevented in all children born in 2002, by combining estimates of the annual
      risk of tuberculosis infection, the proportion of infections that lead to either
      of these diseases in unvaccinated children, the number of children vaccinated,
      and BCG efficacy. FINDINGS: We estimated that the 100.5 million BCG vaccinations
      given to infants in 2002 will have prevented 29,729 cases of tuberculous
      meningitis (5th-95th centiles, 24,063-36,192) in children during their first 5
      years of life, or one case for every 3435 vaccinations (2771-4177), and 11,486
      cases of miliary tuberculosis (7304-16,280), or one case for every 9314
      vaccinations (6172-13,729). The numbers of cases prevented would be highest in
      South East Asia (46%), sub-Saharan Africa (27%), the western Pacific region
      (15%), and where the risk of tuberculosis infection and vaccine coverage are also
      highest. At US2-3 dollars per dose, BCG vaccination costs US206 dollars (150-272)
      per year of healthy life gained. INTERPRETATION: BCG vaccination is a highly cost
      effective intervention against severe childhood tuberculosis; it should be
      retained in high-incidence countries as a strategy to supplement the chemotherapy
      of active tuberculosis.

PMID- 16616561
TI  - Chronic disorders of consciousness.
AB  - The vegetative state and the minimally conscious state are disorders of
      consciousness that can be acute and reversible or chronic and irreversible.
      Diffuse lesions of the thalami, cortical neurons, or the white-matter tracts that
      connect them cause the vegetative state, which is wakefulness without awareness.
      Functional imaging with PET and functional MRI shows activation of primary
      cortical areas with stimulation, but not of secondary areas or distributed neural
      networks that would indicate awareness. Vegetative state has a poor prognosis for
      recovery of awareness when present for more than a year in traumatic cases and
      for 3 months in non-traumatic cases. Patients in minimally conscious state are
      poorly responsive to stimuli, but show intermittent awareness behaviours. Indeed,
      findings of preliminary functional imaging studies suggest that some patients
      could have substantially intact awareness. The outcomes of minimally conscious
      state are variable. Stimulation treatments have been disappointing in vegetative
      state but occasionally improve minimally conscious state. Treatment decisions for
      patients in vegetative state or minimally conscious state should follow
      established ethical and legal principles and accepted practice guidelines of
      professional medical specialty societies.

PMID- 16616563
TI  - Wasting time for wasted children: severe child undernutrition must be resolved in
      non-emergency settings.

PMID- 16616562
TI  - Advancement of global health: key messages from the Disease Control Priorities
      Project.
AB  - The Disease Control Priorities Project (DCPP), a joint project of the Fogarty
      International Center of the US National Institutes of Health, the WHO, and The
      World Bank, was launched in 2001 to identify policy changes and intervention
      strategies for the health problems of low-income and middle-income countries.
      Nearly 500 experts worldwide compiled and reviewed the scientific research on a
      broad range of diseases and conditions, the results of which are published this
      week. A major product of DCPP, Disease Control Priorities in Developing
      Countries, 2nd edition (DCP2), focuses on the assessment of the cost
      effectiveness of health-improving strategies (or interventions) for the
      conditions responsible for the greatest burden of disease. DCP2 also examines
      crosscutting issues crucial to the delivery of quality health services, including
      the organisation, financial support, and capacity of health systems. Here, we
      summarise the key messages of the project.

PMID- 16616564
TI  - A rare and reversible cause of anaemia and renal impairment.

PMID- 16616565
TI  - Characterization and cDNA cloning of hinnavin II, a cecropin family antibacterial
      peptide from the cabbage butterfly, Artogeia rapae.
AB  - Hinnavins, together with lysozymes, are the main types of antibacterial
      peptides/proteins previously isolated from the larval haemolymph of the cabbage
      butterfly, Artogeia rapae as part of the humoral immune response to a bacterial
      invasion. One of these antibacterial peptides, named hinnavin II, was purified
      and characterized after cDNA cloning. The purified hinnavin II was more active
      against Gram negative than against Gram positive bacteria. Hinnavin II also
      showed a powerful synergistic effect on the inhibition of bacterial growth with
      purified lysozyme. The cDNA has a total length of 186 bp with a 114 coding
      region. The deduced protein sequence contains 38 amino acids with a coding
      capacity of 4142.8 Da. The result of a multiple sequence alignment and
      phylogenetic analysis with Clustal W indicated that mature hinnavin II showed an
      approximately 78.9% amino acid sequence identity with cecropin A and originated
      from a group containing mostly lepidopteran cecropins.

PMID- 16616566
TI  - Enhancement of drug delivery to bone: characterization of human tissue
      nonspecific alkaline phosphatase tagged with an acidic oligopeptide.
AB  - Hypophosphatasia is caused by deficiency of activity of the tissue-nonspecific
      alkaline phosphatase (TNSALP), resulting in a defect of bone mineralization.
      Enzyme replacement therapy (ERT) with partially purified plasma enzyme was
      attempted but with little clinical improvement. Attaining clinical effectiveness
      with ERT for hypophosphatasia may require delivering functional TNSALP enzyme to
      bone. We tagged the C-terminal-anchorless TNSALP enzyme with an acidic
      oligopeptide (a six or eight residue stretch of L-Asp), and compared the
      biochemical properties of the purified tagged and untagged enzymes derived from
      Chinese hamster ovary cell lines. The specific activities of the purified enzymes
      tagged with the acidic oligopeptide were the same as the untagged enzyme. In
      vitro affinity experiments showed the tagged enzymes had 30-fold higher affinity
      for hydroxyapatite than the untagged enzyme. Lectin affinity chromatography for
      carbohydrate structure showed little difference among the three enzymes.
      Biodistribution pattern from single infusion of the fluorescence-labeled enzymes
      into mice showed delayed clearance from the plasma up to 18 h post infusion and
      the amount of tagged enzyme retained in bone was 4-fold greater than that of the
      untagged enzyme. In vitro mineralization assays with the bone marrow from a
      hypophosphatasia patient using each of the three enzymes in the presence of high
      concentrations of pyrophosphate provided evidence of bone mineralization. These
      results show the anchorless enzymes tagged with an acidic oligopeptide are
      delivered efficiently to bone and function bioactively in bone mineralization, at
      least in vitro. They suggest potential advantages for use of these tagged enzymes
      in ERT for hypophosphatasia, which should be explored.

PMID- 16616567
TI  - Clinical evaluation of multimodal environmental modification (MEMO) in the
      management of cats with idiopathic cystitis.
AB  - This prospective observational study evaluated client-reported recurrence of
      lower urinary tract signs (LUTS) and other signs of abnormalities in cats with
      idiopathic cystitis after institution of multimodal environmental modification
      (MEMO). Forty-six client-owned indoor-housed cats with idiopathic cystitis,
      diagnosed based on a history of recurrent LUTS and evidence of absence of
      urolithiasis or bacterial urinary tract infection were studied. In addition to
      their usual care, clients were offered recommendations for MEMO based on a
      detailed environmental history. Cases were followed for 10 months by client
      contact to determine the effect of MEMO on LUTS and other signs. Significant
      (P<0.05) reductions in LUTS, fearfulness, nervousness, signs referable to the
      respiratory tract, and a trend (P<0.1) toward reduced aggressive behavior and
      signs referable to the lower intestinal tract were identified. These results
      suggest that MEMO is a promising adjunctive therapy for indoor-housed cats with
      LUTS, and should be followed up with prospective controlled clinical trials.

PMID- 16616568
TI  - Diagnosis and treatment of a feline oral mast cell tumor.
AB  - A cat was diagnosed with an oral mast cell tumor following incisional biopsy. The
      location of the tumor, possible metastasis, financial restraint and patient
      disposition severely limited therapeutic options. The patient was treated with
      six doses of 1-(2-chloroethyl)3-cyclohexyl-1-nitrosurea (CCNU) and
      methylprednisolone acetate. Complete remission was obtained after the third
      dosing regimen. This is the first documented case of feline oral mast cell tumor
      and one of a small group of cats with various cancers to be responsive to CCNU
      treatment.

PMID- 16616569
TI  - Platelet-bound antibodies detected by a flow cytometric assay in cats with
      thrombocytopenia.
AB  - In cats, primary or secondary immune-mediated thrombocytopenia have rarely been
      described or characterised. The objective of this study was to determine platelet
      bound antibodies (PBA) by a flow cytometric assay in both healthy and
      thrombocytopenic cats. Direct PBA testing was performed in 42 thrombocytopenic
      cats (platelet counts 6-179 x 10(9)/l, median 56 x 10(9)/l). Of these 42 cats, 19
      had positive PBA test results, 17 of which were considered to have secondary
      immune-mediated thrombocytopenia (sITP). Underlying diseases included fat
      necroses (four cases), feline infectious peritonitis (three), feline leukaemia
      virus (two) or feline immunodeficiency virus (two) infections, lymphoma (two),
      leukaemia (one), hepatitis (one), pyelonephritis (one), or hyperthyroidism (one).
      In two cats, no underlying disease was found suggesting a primary immune-mediated
      thrombocytopenia (pITP). The PBA test was negative in 23 cats diagnosed with
      varying underlying diseases and in 47 healthy control cats with platelet values
      within the reference range. Only seven of the 42 cats with thrombocytopenia
      (platelet count 10-57 x 10(9)/l, median 34 x 10(9)/l) had spontaneous bleeding.
      This study suggests that immune-mediated destruction of platelets might be an
      important pathological mechanism for feline thrombocytopenia caused by various
      underlying diseases. In cats, pITP appears to be rarely diagnosed.

PMID- 16616570
TI  - [Implication of nurses in transfusion safety: knowledge assessment and practice
      evaluation at the Gustave-Roussy institute].
AB  - BACKGROUND: A first survey on nurses transfusion practices at our Hospital
      revealed poor knowledge. Good Transfusion Practices were written, a training
      program was implemented and a second survey was carried out two years later.
      STUDY DESIGN AN METHODS: We conducted the second survey in which 4 of the
      questions were identical to those in the first survey in order to assess the
      impact of this training strategy. The 4 questions were on blood sample
      identification, checking patient identification, checking "use by date" on blood
      product bag and the pre-transfusion bedside compatibility test. Behaviours were
      evaluated by checking the pre-transfusion procedures, including interpretation of
      bedside compatibility tests. We investigated the impact of attendance at the
      training course, the period of employment, day versus night shift and attempted
      to correlate these factors with the results of the second survey. RESULTS: A
      significant improvement was observed in knowledge of Good Practices between the
      first and the second survey (P = 10(-4)). However, the multivariate analysis
      showed that the impact of training was heterogeneous. Pre-transfusion protocol
      checks have improved significantly (P = 0.05) as well as pre-transfusion bedside
      compatibility test interpretation of ABO compatibility (P = 0.007). CONCLUSION:
      In our study, the implementation of Good practices has significantly improved
      nurses' knowledge about transfusion safety requirements but it is essential to
      continue and adapt the training and cheek regularly the impact of these
      implementations.

PMID- 16616571
TI  - Changes in biochemical, hematological and immunological profiles after low-dose
      intravenous immunoglobulin administration in patients with hypogammaglobulinemia.
AB  - We assessed the immediate effect of intravenous immunoglobulins (IVIG) on the
      biochemical, immunological and hematological profiles in patients with
      hypogammaglobulinemia. Over a period of three months, patients with antibody
      deficiencies, who had been established on stable IVIG treatment as replacement
      therapy in our hospital, were enrolled in the study. Participants underwent pre
      therapy determinations of their biochemical, immunological and hematological
      profiles. Laboratory determinations were repeated after completion of IVIG
      infusions. Over the study period, fourteen patients were enrolled and a total of
      34 pre- and post-IVIG infusion determinations were performed and results
      compared. We found that low-dose IVIG treatment in patients with
      hypogammaglobulinemia results in post-infusion biochemical and hematological
      changes, as follows: an increase in total protein concentration and a reduction
      in albumin, total cholesterol, sodium and alkaline phosphatase concentrations as
      well as lymphocyte and platelet counts. All these biochemical and cellular
      changes seems to be transient, since they were not observed in the subsequent pre
      infusion determination. However, in other patient populations, some of these
      changes might differ, depending on the dose of IVIG administered and the baseline
      condition and immunological status of the patient.

PMID- 16616572
TI  - Letter to the Editor refuting "Epidemiological pattern of classical Borna disease
      and regional genetic clustering of Borna disease viruses point towards the
      existence of to-date unknown endemic reservoir host populations" by Ralf
      Durrwald, Jolanta Kolodziejek, Aemero Muluneh, Sibylle Herzog and Norbert
      Nowotny, Microbes and Infection 8 (2006) 917-929.

PMID- 16616573
TI  - CR3 (CD11b/CD18) is the major macrophage receptor for IgM antibody-mediated
      phagocytosis of African trypanosomes: diverse effect on subsequent synthesis of
      tumor necrosis factor alpha and nitric oxide.
AB  - Immunoglobulin M (IgM) antibodies to the variant surface glycoproteins (VSG) of
      African trypanosomes are the first and predominant class of anti-trypanosomal
      antibodies in the infected host. They are a major factor in controlling waves of
      parasitemia, but not in long-term survival. The macrophage receptor(s) that
      enables phagocytosis of IgM anti-VSG-coated African trypanosomes is unknown. We
      assessed whether complement receptor CR3 (CD11b/CD18) might be involved in
      mediating phagocytosis of Trypanosoma congolense. We show that murine complement
      C3 fragments are deposited onto T. congolense when the trypanosomes are incubated
      with IgM anti-VSG and fresh mouse serum. In the presence of fresh mouse serum,
      there is significantly and markedly less phagocytosis of IgM-opsonized T.
      congolense by CD11b-deficient macrophages compared to phagocytosis by wild-type
      macrophages (78% fewer T. congolense are ingested per macrophage). Significantly
      less tumor necrosis factor (TNF)-alpha (38% less), but significantly more nitric
      oxide (NO) (63% more) are released by CD11b-deficient macrophages that have
      engulfed trypanosomes than by equally treated wild-type macrophages. We conclude
      that CR3 is the major, but not the only, receptor involved in IgM anti-VSG
      mediated phagocytosis of T. congolense by macrophages. We further conclude that
      IgM anti-VSG-mediated phagocytosis of T. congolense enhances synthesis of disease
      producing TNF-alpha and inhibits synthesis of parasite-controlling NO. We suggest
      that signaling of inhibition of NO synthesis is mediated via CR3.

PMID- 16616574
TI  - Immunization with MIC1 and MIC4 induces protective immunity against Toxoplasma
      gondii.
AB  - Host cell invasion by Toxoplasma gondii is tightly coupled to the apical release
      of micronemal proteins (MIC). In this work, we evaluated the protective effect
      encountered in C57BL/6 mice immunized with MIC1 and MIC4 purified from soluble
      tachyzoite antigens by affinity to immobilized lactose. The immunized mice
      presented high serum levels of IgG1 and IgG2b specific antibodies. MIC1/4
      stimulated spleen cells from immunized mice produced IL-2, IL-12, IFN-gamma, IL
      10, but not IL-4, suggesting the induction of a polarized Th1 type immune
      response. When orally challenged with 40 cysts of the ME49 strain, the immunized
      mice had 68% fewer brain cysts than the control mice. Immunization was associated
      with 80% survival of the mice challenged with 80 cysts, contrasting with 100%
      mortality of the non-immunized mice in the acute phase. In this phase, there was
      much lower parasitism in the lungs and small intestine of the immunized mice, and
      they did not exhibit the early-stage signs of intestinal necrosis, which was
      clearly detected in the control mice. Our data demonstrate that MIC1 and MIC4
      triggered a protective response against toxoplasmosis, and that these antigens
      are targets for the further development of a vaccine.

PMID- 16616575
TI  - Bisphosphonate therapy in rheumatoid arthritis.
AB  - Focal bone damage and generalized bone loss are features of rheumatoid arthritis
      (RA). The introduction of TNFalpha antagonists has radically improved the
      management of RA by providing a means of slowing or preventing the occurrence of
      focal bone damage. However, some patients with severe RA have contraindications
      to TNFalpha antagonist therapy and others either fail to respond or fail to
      tolerate TNFalpha antagonists. In addition, whether TNFalpha antagonists
      effectively combat generalized bone loss remains unknown. Bisphosphonates can
      prevent generalized bone loss. Their main target is the osteoclast, which has
      been identified as the culprit in focal bone damage caused by inflammatory
      diseases. As a result, the potential effects of bisphosphonates on focal bone
      damage related to RA are generating strong interest. Although results from the
      few studies in humans have been disappointing, new insights into the mechanisms
      of action of amino-bisphosphonates and recent data obtained in animals, most
      notably with new-generation bisphosphonates, have rekindled the hope that
      bisphosphonates may be beneficial in RA. We review herein the main studies of the
      effects of bisphosphonate therapy on focal bone damage and generalized bone loss
      in patients with RA.

PMID- 16616577
TI  - Positive cooperativity in the cellular uptake of a boronated porphyrin.
AB  - This work was undertaken to assess the kinetics of boronated porphyrin cellular
      uptake, which has been reported to occur by way of the low-density lipoprotein
      receptors. Because of current interest in the use of boronated porphyrins in
      boron neutron capture therapy of tumors, this pathway was investigated for the
      cellular uptake of a boronated porphyrin (tetrakis-carborane-carboxylate, esters
      of 2,4-bis (alpha,beta-dihydroxyethyl) deuteroporphyrin IX). Boron uptake
      occurred even without low-density lipoprotein in the culture medium. Pre
      incubation of V-79 Chinese hamster cells for 24 h in medium containing
      delipidized fetal bovine serum markedly increased the subsequent uptake of boron
      when compared with cells pre-incubated with medium containing 10% fetal bovine
      serum. The increased uptake was characterized by greater affinity for boronated
      porphyrin, compared to cells pre-incubated in 10% fetal bovine serum. Twenty-four
      hour preincubation of cells with increasing concentrations of LDL added to
      delipidized medium suppressed the up-regulation of the boron level. In contrast,
      incubation with added acetylated LDL did not prevent the up-regulation of boron
      uptake. Positive cooperativity was demonstrated by Hill and Scatchard plots. It
      is concluded that uptake of boronated porphyrin is characterized by positive
      cooperativity, that its uptake is markedly enhanced when preincubated in
      delipidized serum, and that significant uptake occurs even in the absence of low
      density lipoprotein in the medium. These data suggest a novel way for enhancing
      uptake of boron (and perhaps other agents) into tissues using carrier porphyrins,
      by increasing the number and/or affinity of cellular LDL receptors.

PMID- 16616578
TI  - Geminivirus disease complexes: the threat is spreading.
AB  - Symptom-modulating DNA satellites associated with geminiviruses have come to our
      attention only recently but have proven to be widespread, associated with many
      diseases throughout the Old World, and economically significant, particularly in
      developing countries. Recent developments are elucidating the role played by
      these novel molecules in pathogenicity and in overcoming host plant defense.
      Further investigation into the promiscuous nature of these satellites and their
      ability to recruit further begomoviruses indicates that regions not yet affected
      by such begomovirus-satellite complexes are at great risk.

PMID- 16616579
TI  - Licensed to kill: the lifestyle of a necrotrophic plant pathogen.
AB  - Necrotrophic plant pathogens have received an increasing amount of attention over
      the past decade. Initially considered to invade their hosts in a rather
      unsophisticated manner, necrotrophs are now known to use subtle mechanisms to
      subdue host plants. The gray mould pathogen Botrytis cinerea is one of the most
      comprehensively studied necrotrophic fungal plant pathogens. The genome sequences
      of two strains have been determined. Targeted mutagenesis studies are unraveling
      the roles played in the infection process by a variety of B. cinerea genes that
      are required for penetration, host cell killing, plant tissue decomposition or
      signaling. Our increasing understanding of the tools used by a necrotrophic
      fungal pathogen to invade plants will be instrumental to designing rational
      strategies for disease control.

PMID- 16616580
TI  - Plant stem cells carve their own niche.
AB  - Stem cells are the precursors of differentiated cells and are, thus,
      indispensable for growth and development in plants and animals. Stem cells from
      both types of organisms share the fundamental features of a capacity for self
      renewal and an ability to generate differentiated cells. The maintenance of stem
      cells in both systems is dependent upon reciprocal signalling between stem cells
      and the specialized tissue microenvironment known as the niche, which provides
      intercellular signals for stem cell regulation. One significantly underexplored
      facet of plant stem cells is the nature of their intrinsic transcriptional
      programme. A potentially rich avenue for addressing this deficiency is to combine
      laser-assisted microdissection and genome-wide transcriptional profiling to
      unravel the molecular road map controlling plant stem cells and their niches.

PMID- 16616581
TI  - trans meets cis in MADS science.
AB  - The interaction between a transcription factor and its binding site at the DNA is
      an integral part of transcriptional regulatory networks, which is fundamental for
      an understanding of biological processes. An example is the family of MADS domain
      transcription factors, which represent key regulators of processes in yeast,
      animals and plants. However, despite our extensive knowledge of these
      transcription factors, limited information is available on the cis-elements to
      which these proteins bind or how these elements are defined. Here, we discuss the
      current understanding of MADS protein binding sites and compare data from various
      organisms. This information can help us in developing algorithms to predict
      binding sites for MADS domain transcription factors, which would be a significant
      step forward in the identification of "down-stream" target genes and the
      elucidation of transcriptional networks.

PMID- 16616582
TI  - Correlation of epiphyllous bud differentiation with foliar senescence in
      crassulacean succulent Kalanchoe pinnata as revealed by thidiazuron and ethrel
      application.
AB  - Leaves of Kalanchoe pinnata have crenate margins with each notch bearing a
      dormant bud competent to develop into a healthy plantlet. Leaf detachment is a
      common signal for inducing two contrastingly different leaf-based processes, i.e.
      epiphyllous bud development into plantlet and foliar senescence. To investigate
      differentiation of bud and its correlation, if any, with foliar senescence,
      thidiazuron (TDZ), having cytokinin activity and ethrel (ETH), an ethylene
      releasing compound, were employed. The experimental system was comprised of
      marginal leaf discs, each harbouring an epiphyllous bud. Most of the growth
      characteristics of plantlet developing from the epiphyllous bud were
      significantly inhibited by TDZ but promoted by ETH. The two regulators modulated
      senescence in a manner different for leaf discs and plantlet leaves. Thus, TDZ
      caused a complete retention whereas ETH a complete loss of chlorophyll in the
      leaf discs. In contrast, the former resulted in a complete depletion of
      chlorophyll from the plantlet leaves producing an albino effect, while the latter
      reduced it by 50% only. In combined dispensation of the two regulators, the
      effect of TDZ was expressed in majority of responses studied. The results
      presented in this investigation clearly show that the foliar processes of
      epiphyllous bud differentiation and senescence are interlinked as TDZ that
      delayed senescence inhibited epiphyllous bud differentiation and ETH that
      hastened senescence promoted it. A working hypothesis to interpret responsiveness
      of the disc-bud composite on lines of a source-sink duo, has been proposed.

PMID- 16616583
TI  - Possible involvement of some secondary metabolites in salt tolerance of
      sugarcane.
AB  - Accumulation of toxic ions in plant tissues modulates the levels of primary and
      secondary metabolites, which may be related to salinity tolerance. In this study
      two sugarcane clones, CP-4333 (tolerant) and HSF-240 (sensitive), were exposed to
      salinity levels at the formative stage, and evaluated three times at 10-day
      intervals. Although net rate of photosynthesis (Pn), leaf area, length and dry
      weight of shoots were decreased in both clones, the CP-4333 showed less reduction
      compared to HSF-240. Both clones displayed a general tendency to accumulate Na+
      and Cl- and little K+, though CP-4333 accumulated less Na+ and more K+ compared
      to HSF-240, and thus showed a higher K+:Na+ ratio. The carotenoid (CAR) content
      remained steady, while total chlorophyll (CHL) was slightly reduced in the
      tolerant clone and significantly reduced in HSF-240. In contrast, soluble
      phenolics (PHE), anthocyanins (ANT) and flavones (FLA) levels were 2.5, 2.8 and
      3.0 times greater in CP-4333 in comparison with HSF-240. The decrease in Pn and
      most secondary metabolites demonstrated by the sensitive clone, but not evidenced
      in the tolerant clones, suggest that the presence of those metabolites is related
      to increased salt tolerance of sugarcane. The increased synthesis of PHE, ANT and
      FLA seems to protect sugarcane from ion-induced oxidative stress, probably due to
      a common structural skeleton, the phenyl group, of those metabolites. CAR, as
      components of the light harvesting center (LHC) and biosynthesized in
      chloroplasts, may confer resistance to this organelle. The PHE, ANT and FLA
      synthesized in the cytosol may protect cells from ion-induced oxidative damage by
      binding the ions and thereby showing reduced toxicity on cytoplasmic structures.

PMID- 16616584
TI  - Salt stress-induced programmed cell death in tobacco protoplasts is mediated by
      reactive oxygen species and mitochondrial permeability transition pore status.
AB  - The status of mitochondrial permeability transition pore (PTP) and levels of
      reactive oxygen species (ROS) play key roles in regulating apoptosis in animal
      cells. To investigate if the PTP and cellular oxidation-reduction state are also
      involved in salt stress-induced programmed cell death (PCD) in tobacco (Nicotiana
      tabacum, cultivar BY-2) protoplasts, flow cytometry was used to simultaneously
      monitor ROS levels, PTP status and PCD. Increased ROS and decreased mitochondrial
      membrane potential (delta psi(m)) were observed before the appearance of PCD. Pre
      treatment with an inhibitor of the PTP opening, cyclosporin A (CsA), effectively
      retarded the onset of PCD, the delta psi(m) decrease and the ROS content
      increase. Addition of ascorbic acid (AsA) during the salt stress significantly
      decreased the percentage of protoplasts undergoing PCD and ROS levels but
      increased delta psi(m). Hydrogen peroxide effectively induced the appearance of
      PCD and caused an increase in ROS and a decrease in delta psi(m). Pre-treatment
      of protoplasts with CsA weakened the effects of H2O2. All these results suggest
      that the open state of PTP and ROS are necessary elements for salt stress-induced
      PCD in tobacco protoplasts. The open states of PTP and ROS could promote each
      other suggesting that ROS could lead to a self-amplifying process. This positive
      feedback loop may act as an all-or-nothing switch, which is in good accordance
      with the hypothesis that PTP is an important coordinator and executioner of PCD
      in both animals and plants.

PMID- 16616585
TI  - Changes in ligno-suberization of cell walls of tomato hairy roots produced by
      salt treatment: the relationship with the release of a basic peroxidase.
AB  - A highly basic peroxidase isoenzyme was shown to be released to the culture
      medium of tomato (Lycopersicon esculentum) hairy roots grown in Murashige-Skoog
      (MS) liquid medium when it was supplemented with 100 mM NaCl. In this paper we
      demonstrate that this enzyme is ionically bound to cell walls and that the
      release was a consequence of the continuous agitation of the tissue in a high
      ionic strength medium with salt addition. In order to establish the physiological
      role of this isoenzyme we partially purified it, and we analysed its kinetic
      properties as coniferyl alcohol peroxidase. The peroxidase isoenzyme showed a
      high catalytic efficiency for this substrate, which suggests that it would be
      associated with the ligno-suberization process. To confirm the involvement of
      this isoenzyme in that process, we studied the pattern of ligno-suberization of
      the tissue under different conditions of growth. Our results suggest that this
      basic peroxidase would be indeed involved in ligno-suberization since its leakage
      from cell walls, induced by 100 mM NaCl in liquid MS, caused less ligno
      suberization of exo and endodermis. On the contrary, more ligno-suberization was
      seen in cell walls when the hairy roots were grown in a salt-supplemented MS
      solid medium without contact with it, a condition in which the release of the
      isoenzyme would be avoided. Thus, through the changes produced by the release of
      the enzyme from its site of action, we could demonstrate the physiological role
      of this peroxidase in the processing of root cell walls, being part of control
      mechanisms of ion and water fluxes through the root.

PMID- 16616586
TI  - Paclobutrazol pre-treatment enhanced flooding tolerance of sweet potato.
AB  - The objective of this experiment was to study changes of antioxidants and
      antioxidative enzymes in the flooding-stressed sweet potato leaf, as affected by
      paclobutrazol (PBZ) treatment at 24 h prior to flooding. Sweet potato 'Taoyuan 2'
      were treated with 0 and 0.5 mg/plant of PBZ, afterwards subjected to non-flooding
      and flooding-stress conditions for 0, 1, 3, and 5 d, followed by a 2 d drainage
      period. The study was conducted as a factorial experiment in completely
      randomized blocks with three replications maintained within a screen house.
      Plants with various antioxidative systems responded differently to flooding
      stress according to the duration of the flooding period and subsequent drainage
      period. The increased levels of antioxidants and antioxidative enzymes observed
      on different days of flooding afforded the sweet potato leaf with improved
      flooding tolerance. Glutathione reductase activity in the leaf was significantly
      enhanced over 5 d continuous flooding followed by a drainage period, in
      comparison with non-flooding conditions. Under non-flooding conditions,
      antioxidative system of leaf was regulated and elevated by PBZ pre-treatment. PBZ
      treatment may enable sweet potato 'Taoyuan 2' to maintain the balance between the
      formation and the detoxification of activated oxygen species. Our results also
      show that under flooding-stress conditions, the level of 'Taoyuan 2'
      antioxidative system is linked to PBZ treatment. Pre-treating with PBZ may
      increase levels of various components of antioxidative systems after exposure to
      different durations of flooding and drainage, thus inducing flooding tolerance.
      PBZ exhibited the important function of enhancing the restoration of leaf
      oxidative damage under flooding stress after the pre-application of 0.5 mg/plant.
      These findings may have greater significance for farming in frequently flooded
      areas.

PMID- 16616587
TI  - Characterization of a protein kinase (FsPK4) with an acidic domain, regulated by
      abscisic acid and specifically located in Fagus sylvatica L. seeds.
AB  - An abscisic acid (ABA)-induced cDNA fragment encoding a putative serine/threonine
      protein kinase (PK) was obtained by means of differential reverse transcriptase
      polymerase chain reaction (RT-PCR). The full-length clone (FsPK4) was isolated
      from a cDNA library constructed using mRNA from ABA-treated Fagus sylvatica L.
      seeds. This clone contained the 11 catalytic domains present in all PKs and a
      highly acidic domain in the C-terminus. By expressing FsPK4 in Escherichia coli
      as a His tag fusion protein, we obtained direct biochemical evidence supporting
      Ca2+-dependent kinase activity of this protein. The expression of FsPK4 increased
      after ABA treatment or warm pre-treatment, when seeds are maintained dormant, but
      decreased and tended to disappear when dormancy was released by stratification or
      under gibberellic acid (GA3) treatment, and when seeds were artificially dried.
      Further, FsPK4 transcript expression is tissue specific, and was found to
      accumulate in ABA-treated seeds rather than in other ABA-treated vegetative
      tissues examined. These results suggest that the expression of the corresponding
      protein could be more closely related with the maintenance of seed dormancy than
      with responses to drought stress mediated by ABA.

PMID- 16616588
TI  - Transcriptional regulation of the sbeIIb genes in sorghum (Sorghum bicolor) and
      barley (Hordeum vulgare): importance of the barley sbeIIb second intron.
AB  - The transcriptional activity of the sorghum sbeIIb gene, encoding starch
      branching enzyme IIb, is seed specific, with expression in both the endosperm and
      the embryo. In comparison, expression of barley sbeIIb is confined to the
      endosperm, whereas that of barley sbeIIa occurs in endosperm, embryonic and
      vegetative tissues. It has been suggested that the second intron of barley sbeIIb
      may be instrumental in conferring endosperm-specific expression. Therefore, to
      further investigate the regulatory mechanisms of barley and sorghum sbe, we
      examined the tissue-specific activity of the sorghum sbe promoter in transient
      assays of green fluorescent protein (gfp) reporter constructs. We found that,
      when linked to the barley sbeIIb second intron, the sorghum sbeIIb promoter could
      not drive gfp transcription in sorghum or barley embryonic cells. Similar results
      were obtained for the barley sbeIIa promoter. Database searches showed that
      sequences homologous to the barley sbeIIb intron also exist in introns and
      flanking regions of some other grass genes. Deletion mutagenesis of the sorghum
      sbeIIb promoter identified the minimal promoters required for high- and low-level
      expression, respectively, but did not reveal any putative promoter elements
      crucial for expression. A sequence with similarity to the SURE element,
      implicated in sugar signaling, was located in the distal promoter region of
      sorghum sbeIIb, upstream of the minimal promoters. SURE elements are present in
      the proximal promoter regions of the sugar-regulated barley iso1 gene, and barley
      sbeIIb. In keeping in line with these observations, RNA-gel blot analyses
      demonstrated that expression of barley sbeIIb was sugar inducible, whereas that
      of sorghum sbeIIb was not.

PMID- 16616589
TI  - Aluminium-induced drought and oxidative stress in barley roots.
AB  - The aim of the present study was to examine the relation between Al accumulation
      in root tissues, root growth inhibition, root water content, cell viability and
      expression of oxidative and drought stress-related genes in barley roots growing
      on the filter paper. Al-induced root growth inhibition correlated with Al uptake
      and cell death. Water content of Al-treated root represented only half of the
      control one. The expression of the dehydrin gene dhn4, which is a marker for
      drought stress in plant tissues, was strongly induced during Al stress. Al
      treatment also induced expression of oxidative stress-related genes such as
      glutathione peroxidase (gpx), pathogen-related peroxidase (prx8), glutathione
      reductase (gr) and dehydroascorbate reductase (dhar). The present results suggest
      correlation between Al uptake, Al-induced drought stress, oxidative stress, cell
      death and root growth inhibition.

PMID- 16616590
TI  - Implicit learning and statistical learning: one phenomenon, two approaches.
AB  - The domain-general learning mechanisms elicited in incidental learning situations
      are of potential interest in many research fields, including language
      acquisition, object knowledge formation and motor learning. They have been the
      focus of studies on implicit learning for nearly 40 years. Stemming from a
      different research tradition, studies on statistical learning carried out in the
      past 10 years after the seminal studies by Saffran and collaborators, appear to
      be closely related, and the similarity between the two approaches is strengthened
      further by their recent evolution. However, implicit learning and statistical
      learning research favor different interpretations, focusing on the formation of
      chunks and statistical computations, respectively. We examine these differing
      approaches and suggest that this divergence opens up a major theoretical
      challenge for future studies.

PMID- 16616591
TI  - The interplay between structure-based design and combinatorial chemistry.
AB  - The two most lauded drug design approaches from the past century--structure-based
      design and combinatorial chemistry--are increasingly experiencing integration,
      whereby the three-dimensional coordinates of a receptor supports the development
      of combinatorial-based ligand design. A selective polling of the recent
      literature demonstrates that this can be actualized in many ways.

PMID- 16616592
TI  - The role and value of endorectal ultrasonography in diagnosing T1 rectal tumors.
AB  - Rectal carcinoma in 50% to 60% of cases is localized in the rectum and, if
      diagnosed early can be locally excised. The authors evaluated the diagnostic
      accuracy of the preoperative endorectal ultrasonography (ERUS) in the staging of
      rectal tumors and the usefulness of the method to assess patients' suitability
      for local excision. In the retrospective analysis, we analyzed 29 patients with
      rectal cancer. The depth of invasion into the rectal wall was assessed by ERUS
      and all patients were qualified for tumor excision with transanal endoscopic
      microsurgery (TEM). We analyzed overall accuracy of ERUS and the effectiveness of
      treatment. In the analyzed group, diagnostic accuracy of ERUS in assessing T1
      carcinomas was 89.2%, sensitivity 92.3% and specificity 50%. Local excision with
      TEM was deemed to be curative in 86.2% patients with rectal tumors detected by
      ERUS. ERUS is an accurate method of preoperative assessment of T1 and T2
      carcinomas and its diagnostic accuracy is sufficient to qualify patients for anal
      saving operations.

PMID- 16616593
TI  - Serial ultrasound assessment of the basal vein of Rosenthal in HSV encephalitis.
AB  - Herpes simplex virus encephalitis (HSVE) typically affects the baso-temporal
      brain. The venous blood drainage of this region mainly occurs via the basal vein
      of Rosenthal (BVR), which can easily be monitored by transcranial color-coded
      duplex sonography (TCCS), and might be a useful parameter for the activity of the
      disease. Serial blood flow velocity (BFV) measurements of the BVR and the basal
      cerebral arteries were performed in five acute HSVE patients by means of
      transcranial color-coded duplex sonography (TCCS). Remarkable increased BFV of
      the BVR at the affected side was found in all patients, showing a maximum within
      the first 8 d of infection followed by a tendency toward normalisation during the
      next weeks. In comparison, changes of BFV in the basal cerebral arteries were
      much more heterogeneous. Our findings suggest that TCCS measurements of the BVR
      might be used as an additional diagnostic bed-side tool to evaluate patients with
      HSVE during the acute stage.

PMID- 16616594
TI  - Tetra-layered sign of adult intussusception (new ultrasound approach).
AB  - Two-dimensional ultrasound is the principle method for the detection of
      intussusception. The aim of this study was to establish a pathognominic
      ultrasound criterion for diagnosing intestinal intussusception to facilitate a
      proper clinical decision. We have developed a new approach to diagnosing colonic
      intussuception based on the hypothesis that ultrasound image of the invaginated
      segment should reveal four border layers. We called this sign tetra-layered sign
      (TLS). In a prospective manner, all adult patients diagnosed with intussusception
      using the TLS approach in the period from July 1990 and July 2005 were included
      in this study. All patients underwent explorative laparotomy, and our
      preoperative diagnoses were compared with the surgical outcome. Thirty patients
      were diagnosed with intestinal intussusception using the TLS ultrasound sign.
      Surgery confirmed the preoperative diagnosis in all cases. Conventional
      ultrasound is very reliable in diagnosing intestinal intussusception in adult
      patients when utilizing the simple ultrasound applicable TLS. This facilitates
      the decision-making, improves the clinical outcome and reduces the associated
      costs.

PMID- 16616595
TI  - Cardiac motion analysis from ultrasound sequences using nonrigid registration:
      validation against Doppler tissue velocity.
AB  - Early detection of cardiac motion abnormalities is one of the main goals of
      quantitative cardiac image processing. This article presents a new method to
      compute the 2-D myocardial motion parameters from gray-scale 2-D
      echocardiographic sequences, making special emphasis on the validation of the
      proposed technique in comparison with Doppler tissue imaging. Myocardial motion
      is computed using a frame-to-frame nonrigid registration technique on the whole
      sequence. The key feature of our method is the use of an analytical
      representation of the myocardial displacement based on a semilocal parametric
      model of the deformation using Bsplines. Myocardial motion analysis is performed
      to obtain displacement, velocity and strain parameters. Robustness and speed are
      achieved by introducing a multiresolution optimization strategy. To validate the
      method, velocity measurements in three different regions-of-interest in the
      septum have been compared with those obtained with Doppler tissue velocity in
      healthy and pathologic subjects. Regression and Bland-Altman analysis show very
      good agreement between the two different approaches, with the great advantage
      that the new method overcomes the angle-dependency limitations of the Doppler
      techniques, providing both longitudinal and radial measurements.

PMID- 16616596
TI  - Nonlinear intravascular ultrasound contrast imaging.
AB  - Nonlinear contrast agent imaging with intravascular ultrasound (IVUS) is
      investigated using a prototype IVUS system and an experimental small bubble
      contrast agent. The IVUS system employed a mechanically scanned single element
      transducer and was operated at a 20 MHz transmit frequency (F20) for second
      harmonic imaging (H40), and at a 40 MHz transmit frequency (F40) for subharmonic
      imaging (SH20). Characterization experiments were performed with agent and tissue
      phantom signals acquired during transducer rotation. The suppression of transmit
      frequency tissue signals was achieved using a combination of pulse-inversion and
      bandpass filtering. H40 was found to improve the contrast-to-tissue signal ratio
      (CTR) by up to 22 dB relative to F20, but suffered from tissue propagation
      harmonics at higher pressures (>0.3 MPa). SH20 was also shown to be possible at a
      range of pressures (approximately 0.25 to 1.8 MPa), with tissue signals
      suppressed to near the noise floor. Coronary phantom experiments demonstrated the
      detection of agent in 1 mm diameter vessels outside a larger 4 mm diameter vessel
      in which the IVUS catheter was situated. These results suggest the feasibility of
      harmonic IVUS contrast imaging, which may have applications in coronary lumen
      boundary detection and vasa vasorum imaging.

PMID- 16616597
TI  - Detecting broken struts of a Bjork-Shiley heart valve using ultrasound: a
      feasibility study.
AB  - The Bjork-Shiley (BScc) mechanical heart valve has extensively been used in
      surgery from 1979 to 1986. There is, compared with equivalent valve types,
      increased occurrence of unexpected mechanical failure of the outlet strut of the
      valve, with a high incidence of mortality, when it occurs. Many approaches have
      been attempted to noninvasively determine BScc valve integrity. None of the
      approaches resulted in adequate assessment, mostly due to a lack of either
      sensitivity or specificity demonstrated in in vitro and/or in vivo studies. In
      our study we analyze leg movement of the BScc valves outlet strut during the
      cardiac cycle with ultrasound. For a broken strut, the movement of both legs will
      be significantly different, whereas the difference will be negligible for an
      intact strut. BScc valves were mounted in the mitral position in an in vitro
      pulse duplicator system. A focused single-element transducer was used to direct
      ultrasound on a leg of the outlet strut. Correlation-based time delay estimation
      was used to estimate differences in time of flight of the outlet strut echoes to
      determine outlet strut leg movement. The movement of an intact valve and a valve
      with a single-leg fracture with both ends grating against each other (SLF), the
      most difficult fracture to diagnose, has been studied. The results showed no
      significant difference in movement between both legs of the outlet strut of the
      intact BScc valve (amplitude of movement 9.2 microm +/- 0.1 microm). Whereas for
      the defective valve, the amplitude of movement of the broken leg of the SLF valve
      was 12 microm +/- 1.6 microm vs. 8.6 microm +/- 0.1 microm for the intact leg. In
      conclusion, the proposed method has shown to be feasible in vitro and has
      potentials for in vivo detection of BScc valve outlet strut fracture.

PMID- 16616598
TI  - In vitro strain measurement in the porcine antrum using ultrasound doppler strain
      rate imaging.
AB  - Strain rate imaging (SRI) enables study of deformation in soft tissues. The aim
      of this study was to evaluate the accuracy of SRI in measuring strain in the
      porcine antral wall in vitro. An experimental set-up enabled controlled
      distension of a porcine stomach in a saline reservoir. Radial strain obtained by
      SRI was compared with radial strain calculated from B-mode ultrasonography.
      Circumferential strain obtained by SRI was compared with circumferential strain
      calculated from sonomicrometry. The agreement between radial strain values
      measured by SRI and B-mode, along and across several ultrasound (US) beams, using
      US frequency 6.7 MHz and strain length (SL) = 1.9 mm was = -1.0 +/- 12.1% and 0.5
      +/- 13.4%, respectively (mean difference +/- 2SD%) and it was better than with SL
      1.2 mm. Compared with sonomicrometry, SRI-determined circumferential strain using
      6.7 MHz and SL = 1.9 mm was less accurate, whether averaging along or across
      several US beams (-9.2 +/- 46.7% and 13.8 +/- 51.2%, respectively). In
      conclusion, SRI gave accurate measurement of radial strain of the antral wall,
      but seemed to be less accurate for measurement of circumferential strain for this
      in vitro set-up.

PMID- 16616599
TI  - Quantitative ultrasound and peripheral bone densitometry in patients with genetic
      disorders.
AB  - The aim of the study was comparison of quantitative ultrasound and densitometric
      peripheral measurements in subjects with genetic disorders. The study included 52
      subjects (35 boys and 17 girls) in mean age 13.1 +/- 4.8 y. Patients with
      following disorders were evaluated: Down syndrome (n = 21), Martin-Bell syndrome
      (n = 14) and other (n = 17). There were no additional factors potentially
      influencing bone metabolism. Bone status was assessed by quantitative ultrasound
      at the hand phalanges using DBM Sonic 1200 (IGEA, Italy), which measures
      amplitude-dependent speed of sound (Ad-SoS [m/s]) and bone densitometry at the
      calcaneus and forearm by the use of PIXI (GE, USA), which measures bone mineral
      density (BMD, g/cm2). Ad-SoS correlated significantly with forearm and calcaneus
      BMD in the whole group (r = 0.66, p < 0.000001 and r = 0.51, p < 0.0001,
      respectively), in females (r = 0.58, p < 0.05 and r = 0.5, p < 0.05) and in males
      (r = 0.70, p < 0.000001 and r = 0.54, p < 0.001). Calcaneus BMD correlated with
      wrist BMD in the whole group, in females and males: r = 0.66, p < 0.000001, r =
      0.67, p < 0.01 and r = 0.75, p < 0.0001, respectively. These coefficients of
      correlation were compared and did not reveal significant differences in the whole
      group and in the gender subgroups. ROC analysis of Ad-SoS values versus calcaneus
      and forearm BMD showed area under curve 0.89 for forearm BMD and 0.79 for
      calcaneus BMD (subjects with Ad-SoS T-score below -3.2 were considered as
      abnormal). Age correlated significantly with Ad-SoS, forearm and calcaneus BMD (r
      ranged from 0.53 to 0.9, p from 0.05 to 0.000001). In all patients and males, age
      more strongly influenced Ad-SoS than calcaneus BMD (p < 0.05). Also, body weight
      and height correlated significantly with Ad-SoS, forearm and calcaneus BMD,
      except for correlation between forearm BMD and height in female patients (r from
      0.58 to 0.84, p < 0.05). Generally, in multiple stepwise regression analysis of
      age and body size on skeletal parameters, age had positive influence, and body
      size was a positive or a negative factor. In conclusion, both quantitative
      ultrasound and peripheral densitometry may be recommended for the assessment of
      skeletal status in subjects with genetic disorders, although measurements of
      phalanges seem to be more sensitive for detecting age-related bone changes.

PMID- 16616600
TI  - 3D elastography using freehand ultrasound.
AB  - We present an elastography system using freehand 3D ultrasound. A review is
      provided of the standard elastography methods that have been adapted for this
      purpose. The scanning protocol is simple and promising results are presented of
      3D strain images from freehand scans. Robustness is a problem, however, and the
      main sources of error are explained. Measures have been developed to improve the
      quality of the freehand images by means of drop-out correction and frame
      filtering. Results from the application of these techniques provide an indication
      of development strands which should lead to a system that is both easy-to-use and
      produces reliable, high quality images.

PMID- 16616601
TI  - Towards an acoustic model-based poroelastic imaging method: I. Theoretical
      foundation.
AB  - The ultrasonic measurement and imaging of tissue elasticity is currently under
      wide investigation and development as a clinical tool for the assessment of a
      broad range of diseases, but little account in this field has yet been taken of
      the fact that soft tissue is porous and contains mobile fluid. The ability to
      squeeze fluid out of tissue may have implications for conventional elasticity
      imaging, and may present opportunities for new investigative tools. When a
      homogeneous, isotropic, fluid-saturated poroelastic material with a linearly
      elastic solid phase and incompressible solid and fluid constituents is subjected
      to stress, the behaviour of the induced internal strain field is influenced by
      three material constants: the Young's modulus (E(s)) and Poisson's ratio (nu(s))
      of the solid matrix and the permeability (k) of the solid matrix to the pore
      fluid. New analytical expressions were derived and used to model the time
      dependent behaviour of the strain field inside simulated homogeneous cylindrical
      samples of such a poroelastic material undergoing sustained unconfined
      compression. A model-based reconstruction technique was developed to produce
      images of parameters related to the poroelastic material constants (E(s), nu(s),
      k) from a comparison of the measured and predicted time-dependent spatially
      varying radial strain. Tests of the method using simulated noisy strain data
      showed that it is capable of producing three unique parametric images: an image
      of the Poisson's ratio of the solid matrix, an image of the axial strain (which
      was not time-dependent subsequent to the application of the compression) and an
      image representing the product of the aggregate modulus E(s)(1-nu(s))/(1+nu(s))(1
      2nu(s)) of the solid matrix and the permeability of the solid matrix to the pore
      fluid. The analytical expressions were further used to numerically validate a
      finite element model and to clarify previous work on poroelastography.

PMID- 16616602
TI  - High frequency nonlinear scattering from a micrometer to submicrometer sized
      lipid encapsulated contrast agent.
AB  - An experimental lipid encapsulated contrast agent comprised substantially of
      micrometer to submicrometer diameter bubbles was evaluated for its capacity to
      produce nonlinear scattering in response to high transmit frequencies. Agent
      characterization experiments were conducted at transmit frequencies of 20 and 30
      MHz with bandwidths of 5, 15 and 25% using a broadband focused PVDF transducer.
      The presence of subharmonic energy was observed for all bandwidths at a wide
      range of pressures (0.49 to 5.7 MPa and 0.45 to 4.5 MPa for the 20 and 30 MHz
      cases, respectively). Distinct ultraharmonics were observed only in the 5%
      bandwidth cases. Second harmonic energy was also present, but this was at least
      partly due to nonlinear propagation, as indicated by linear scatterer signals.
      Evidence of destruction was found only at higher peak negative pressures (e.g.,
      >2 MPa for 30 MHz 5% bandwidth pulse). The results suggest that small lipid
      bubble formulations may be useful for the purposes of high frequency nonlinear
      contrast imaging.

PMID- 16616603
TI  - Nanointerrogation of ultrasonic contrast agent microbubbles using atomic force
      microscopy.
AB  - Predicting the acoustic response of an encapsulated microbubble to ultrasound
      requires an accurate assessment of the mechanical properties of the microbubble
      shell. Atomic force microscopy (AFM) provides an unprecedented spatial and force
      resolution of the order of Angstroms and subnanonewtons, respectively. It is
      introduced here as a means to interrogate microbubbles manufactured for
      ultrasonic imaging. The advantage of AFM over scanning electron microscopy (SEM)
      is that the microbubbles need not be subjected to a low temperature or low
      pressure environment. The microbubbles were interrogated in a liquid environment,
      which could potentially be a simulated physiological environment. AFM was used in
      tapping mode imaging to reveal topographical detail of biSphere microbubbles.
      Because microbubbles are large objects compared with the overall size of usual
      AFM tips, a convolution between the AFM tip and the microbubble was typical of
      the acquired topographies. However, a part of the top half of the bubble was
      imaged with nanometer resolution, and roughness measurements are reported. Force
      distance curves were captured using contact mode AFM. The range of stiffness or
      effective spring constant of biSphere was found to be between 1 and 6 N m(-1). In
      conclusion, the AFM is proposed here for the first time as a tool to image the
      surface of bubbles at the nanometer range in liquid and to perform reproducible
      measurements on the mechanical properties of individual microbubbles.

PMID- 16616604
TI  - Effects of low-intensity focused ultrasound on the mouse submandibular gland.
AB  - Ultrasound is expected to make a considerable contribution to drug delivery
      systems (DDSs). We tested the hypothesis that low-intensity focused ultrasound
      (LIFU) increases vessel permeability in the mouse submandibular gland without
      causing parenchymal damage. In a preliminary study, LIFU at 3 W/cm2 with a 50%
      duty cycle for 2 minutes did not cause histologic damage. We therefore applied
      LIFU to mouse submandibular gland at these conditions before and after injecting
      horseradish peroxidase. Single labeling laser scanning confocal microscopy
      revealed positive horseradish peroxidase staining around the excretory ducts in
      the mucous-producing part of the gland, but absence of staining in control
      glands. Immunostaining for fibrinogen was positive in the same region. Fibrinogen
      is an intravascular protein that does not pass through intact vessels. These
      findings suggest that LIFU increases vessel permeability and disruption without
      destruction. It is anticipated that this process will be useful in establishing a
      DDS that uses LIFU.

PMID- 16616605
TI  - Feasibility study of effect of ultrasound on water chestnuts.
AB  - Water chestnut (Trapa natans L.), an annual aquatic plant with floating leaves
      was first introduced into North America in 1874. Since then, wild populations
      have quickly become established in many locations within Northeastern USA. Due to
      its detrimental effects on the overall health of aquatic ecosystems, millions of
      dollars have been spent to control the water chestnut infestations in the North
      America through mechanical harvesting and manual removal, with limited success.
      The potential for continued expansion of the infestations demonstrates an urgent
      need for an effective control method. This study examined the potential of
      ultrasound application as an alternative control strategy for water chestnut
      management. Various frequencies and amplitudes of ultrasound generated by
      submerged transducers were applied directly to water chestnuts harvested from
      Lake Champlain. Substantial damages on water chestnut cells as well as penetrated
      petitoles were observed at the following tested frequencies of ultrasound, 20
      kHz, 187 kHz, 469 kHz, 519 kHz and 2.34 MHz. Among them, 20 kHz ultrasound of 1.9
      MPa acoustic pressure amplitude demonstrated the most significant damages within
      10 s of ultrasound exposure. The treated plants started to die within 72 h and
      the mortality rate of water chestnut plants treated with the ultrasound
      application was 100%.

PMID- 16616606
TI  - The frequency dependence of ultrasonic velocity and the anisotropy of dispersion
      in both freshly excised and formalin-fixed myocardium.
AB  - The objectives of this study were to measure the frequency dependence of the
      ultrasonic velocity in myocardium and to quantify the frequency dependence of
      phase velocity as a function of the insonification angle relative to the
      predominant direction of the myofibers. Broadband phase spectroscopy data were
      acquired, spanning a frequency range of 3 to 8 MHz. Measurements were made on 36
      tissue specimens cored from 12 freshly excised lamb hearts and were repeated
      after fixation with formalin. Measured phase velocities were found to be well
      characterized by a logarithmic fit. For freshly excised myocardium, the
      dispersion over the 3 to 8 MHz bandwidth was dependent on the direction of
      insonification, ranging from 1.2 m/s change for perpendicular insonification
      (across the myofibers) to 3.7 m/s for parallel insonification (along the
      myofibers). The effects of formalin-fixation resulted in a significant increase
      in dispersion for perpendicular insonification, but did not appreciably alter the
      dispersion for parallel insonification.

PMID- 16616607
TI  - Put the metal to the petal: metal uptake and transport throughout plants.
AB  - Compared to other organisms, plants have expanded families of transporters that
      are involved in the uptake and efflux of metals. Fortunately, in many cases, the
      examination of double mutants has been sufficient to overcome the challenge of
      studying functionally redundant gene families. Plants that lack two heavy-metal
      transporting P-type ATPase family members (HMA2 and HMA4) reveal a function for
      these transporters in Zn translocation from roots to shoots. Likewise, the
      phenotype of plants that lack two natural resistance associated macrophage
      protein (NRAMP) homologs (NRAMP3 and NRAMP4) implicate these metal uptake
      proteins in the mobilization of vacuolar Fe stores during seed germination. Most
      families of metal transporters are ubiquitous but the Yellow Stripe1-Like (YSL)
      family is plant specific and YSL family members have been implicated in the
      transport of metals that are complexed with a plant specific chelator called
      nicotianamine (NA).

PMID- 16616608
TI  - Plant carotenoid cleavage oxygenases and their apocarotenoid products.
AB  - The oxidative cleavage of carotenoids leads to the production of apocarotenoids
      and is catalyzed by a family of carotenoid cleavage dioxygenases (CCDs). CCDs
      often exhibit substrate promiscuity, which probably contributes to the diversity
      of apocarotenoids found in nature. Biologically and commercially important
      apocarotenoids include the phytohormone abscisic acid, the visual and signaling
      molecules retinal and retinoic acid, and the aromatic volatile beta-ionone.
      Unexpected properties associated with the CCD catalytic products emphasize their
      role in many aspects of plant growth and development. For instance, CCD7 and CCD8
      produce a novel, graft-transmissible hormone that controls axillary shoot growth
      in plants. Here, CCDs are discussed according to their roles in the biosynthesis
      of these products. Recent studies regarding their mechanism of action are also
      addressed.

PMID- 16616609
TI  - Copper cofactor delivery in plant cells.
AB  - Copper (Cu) is a micronutrient that has roles in photosynthesis, respiration,
      antioxidant activity, cell wall metabolism and hormone perception. Excess Cu is
      toxic and therefore its delivery has to be tightly regulated. Recent progress in
      the study of Cu homeostasis has revealed not only components of the Cu delivery
      machinery but also regulatory systems that control Cu-protein expression and
      coordinate the activity of Cu-delivery systems. The response of photosynthetic
      organisms to Cu deficiency indicates the existence of cross-talk between metal
      cofactor delivery pathways. Next to its well-established roles in plant
      metabolism, a novel function for Cu, first discovered in plants, is in the
      biogenesis of molybdenum cofactor. Defects in Cu delivery factors also suggest
      important roles for Cu in cell expansion.

PMID- 16616610
TI  - Analysis of LMP1 variants of EBV in Southern Thailand: evidence for strain
      associated T-cell tropism and pathogenicity.
AB  - BACKGROUND: The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) has
      sequence heterogeneity. Some of the variants are associated with altered
      tumorigenic activity and show geographically specific localization. In Thailand,
      the EBV genome is frequently detected in circulating T cells of T-cell diseases.
      OBJECTIVE: To determine the role of EBV LMP1 variation in the genesis of T-cell
      diseases, we focused on virus factors and analyzed EBV strains in Thailand. STUDY
      DESIGN: EBV DNA was extracted from 18 healthy individuals and 45 patients with T
      cell diseases in Southern Thailand and 30 healthy individuals in Central
      Thailand. By using PCR-direct sequencing method, nucleotide sequences
      corresponding to the carboxyl terminus of the LMP1 were determined. RESULTS: Four
      known strains, B95-8 prototype, China 1, China 2 and Mediterranean (Med) and two
      novel strains, Southeast Asia 1 (SEA 1) and Southeast Asia 2 (SEA 2) were
      identified. The prevalence of China 2 strain was significantly different
      (p=0.006) between Central and Southern Thailand. Higher prevalence (p=0.026) of
      30-bp deletion type in the Southern Thais was observed. The LMP1 Med strain was
      associated with the worse prognosis (p=0.029). Among T-cell diseases patients,
      CD3(+)-cell oriented infection was recognized in SEA1 strain (p=0.025).
      CONCLUSION: The distribution of EBV strains may be associated with
      geographic/ethnic and clinical background in the Thai population. Certain EBV
      strains defined by their LMP1 sequence may influence cell tropism, disease
      association, or disease severity.

PMID- 16616611
TI  - Identification of a novel variant of human hepatitis E virus in Hungary.
AB  - First human case of hepatitis E infection detected in Hungary is reported. This
      hepatitis E virus (HEV), Hungary1, belongs to genotype 3 and had 95% and 90%
      nucleotide identity within the capsid region of the European swine and human
      (Greece2) strains, respectively. Hungary1 represents a potential novel human
      variant of HEV in genus Hepevirus.

PMID- 16616612
TI  - European seroepidemiology network 2: Standardisation of assays for
      seroepidemiology of varicella zoster virus.
AB  - BACKGROUND: The aim of the European Sero-Epidemiology Network (ESEN2) is to
      harmonise the serological surveillance of vaccine-preventable diseases in Europe.
      OBJECTIVE: To allow comparison of antibody prevalence in different countries by
      standardising results into common units. STUDY DESIGN: For varicella zoster virus
      (VZV), a reference laboratory established a panel of 148 samples, characterised
      by indirect enzyme-immunoassay (ELISA), indirect immunofluorescence, and
      complement fixation test. Fifty-seven samples were also studied by the
      fluorescence antibody to membrane antigen test. The geometric mean of the
      antibody activity (GMAA) obtained from four ELISA determinations was used to
      characterise each sample of the panel as positive (GMAA: >100 mIU/ml), equivocal
      (GMAA: 50-100 mIU/ml) or negative (GMAA: <50 mIU/ml) for antibody to VZV (anti
      VZV). Thirteen laboratories, using five different ELISA tests, tested the panel.
      RESULTS: Agreement with the reference laboratory was above 85% in all cases, and
      the R(2) values obtained from regression analysis of the quantitative results
      were always higher than 0.87. Finally, the regression equations could be used to
      convert national values into a common unitage. CONCLUSION: This study confirmed
      that results for anti-VZV obtained by different ELISA methods can be converted
      into common units, enabling the comparison of the seroprevalence profiles
      obtained in the participant countries.

PMID- 16616613
TI  - Differential display of genes expressed in the filarial nematode Litomosoides
      sigmodontis reveals a putative phosphate permease up-regulated after depletion of
      Wolbachia endobacteria.
AB  - Mutualist symbiotic Wolbachia endobacteria are found in most filarial nematodes.
      Wolbachia are essential for embryogenesis and for larval development into adults,
      and thus represent a new target for anti-filarial drug development. Tetracycline
      antibiotics deplete Wolbachia in animal model filaria Litomosoides sigmodontis
      and Brugia pahangi, as well as in the human parasites Brugia malayi, Onchocerca
      volvulus and Wuchereria bancrofti. Very little is known about the molecular
      details of the symbiotic interaction between Wolbachia and filarial nematodes.
      Nematode genes that respond to anti-Wolbachia antibiotic treatment may play
      important roles in the symbiosis. Differential display PCR was used to detect
      several candidate genes that are up-regulated after 3, 6, 15, 30 and 36 days of
      tetracycline treatment. One of these genes, Ls-ppe-1, was similar to a family of
      phosphate permeases, and had putative orthologues in O. volvulus and B. malayi.
      Ls-ppe-1 steady-state mRNA levels were elevated by day 3-6 of treatment, and
      remained elevated through to 70 days post-treatment. In Caenorhabditis elegans,
      the knockdown of a homologous phosphate permease results in embryonic lethality,
      with the production of degenerating embryos, a phenotype also seen in filarial
      nematodes after depletion of Wolbachia with tetracycline. The potential role of
      Ls-ppe-1 in the nematode-bacterial symbiosis is discussed.

PMID- 16616614
TI  - A new framework for research leading to sports injury prevention.
AB  - This paper proposes a new sports injury research framework, the Translating
      Research into Injury Prevention Practice framework, or TRIPP. This model builds
      on the fact that only research that can, and will, be adopted by sports
      participants, their coaches and sporting bodies will prevent injuries. Future
      advances in sports injury prevention will only be achieved if research efforts
      are directed towards understanding the implementation context for injury
      prevention, as well as continuing to build the evidence base for their efficacy
      and effectiveness of interventions. There is no doubt that intervention research
      in the sporting field can be difficult and many challenges need to be overcome;
      however, that should not be put up as a barrier towards undertaking it. Over the
      next few years, sports injury researchers will need to think carefully about the
      "best" study designs and analysis tools to achieve this. All reported sports
      injury studies, of whatever design, should include information on key
      implementation factors such as player/club recruitment rates and other biases as
      well as the rate of uptake of the interventions being tested, including reasons
      for use/non-use. However, it will only be broad research endeavours that adopt
      the TRIPP six-staged approach that will lead to real-world injury prevention
      gains.

PMID- 16616615
TI  - The public health impact of injury during sport and active recreation.
AB  - Injuries can be an adverse outcome of participation in sport and recreational
      activities. The aim of this study was to determine the public health impact of
      injury during sports and active recreation injury in a select population in
      Australia. A random household telephone survey was conducted quarterly over a 12
      month period in a well-defined geographic region, the Latrobe Valley, Australia.
      Information was collected on participation in sport and active recreation and
      associated injuries over the previous 2 weeks for all household members aged over
      4 years. Injury rates were calculated per 10,000 population and per 1000 sports
      participants. Data were collected on 1084 persons from 417 households. Overall,
      648 people reported participating in at least one sport or active recreation and
      34 (5.2%, 95% CI: 4.8, 5.6%) of these sustained an injury during this activity.
      Overall, 51.4% of injured cases had a significant impact: 26.5% sought treatment,
      34.4% had their activities of daily living adversely affected and 36.0% had their
      performance/participation limited. Cricket (51 injuries/10,000 population), horse
      riding (29/10,000 population) and basketball (25/10,000 population) had the
      highest injury rates. After adjusting for participation, cricket (242
      injuries/1000 participants), horse riding (122/1000 participants) and soccer
      (107/1000 participants) had the highest injury rates. Cricket and soccer were the
      sports most associated with 'significant' injuries. Injury prevention efforts
      should be aimed at team ball sports (especially cricket, soccer and netball)
      because of their comparatively high rate of both overall and 'significant'
      injury.

PMID- 16616616
TI  - Methods to adjust for bias and confounding in critical care health services
      research involving observational data.
AB  - Observational data are often used for research in critical care. Unlike
      randomized controlled trials, where randomization theoretically balances
      confounding factors, studies involving observational data pose the challenge of
      how to adjust appropriately for the bias and confounding that are inherent when
      comparing two or more groups of patients. This paper first highlights the
      potential sources of bias and confounding in critical care research and then
      reviews the statistical techniques available (matching, stratification,
      multivariable adjustment, propensity scores, and instrumental variables) to
      adjust for confounders. Finally, issues that need to be addressed when
      interpreting the results of observational studies, such as residual confounding,
      causality, and missing data, are discussed.

PMID- 16616617
TI  - Do specialist transport personnel improve hospital outcome in critically ill
      patients transferred to higher centers? A systematic review.
AB  - PURPOSE: The aim of the study was to determine whether the use of specialist
      transport personnel improves patient outcome at the receiving hospital for
      critically ill patients transferred to higher centers. MATERIALS AND METHODS: A
      search of 6 electronic databases, 15 relevant journals, and the reference lists
      of all retrieved articles was conducted for studies comparing outcome at the
      receiving hospital for critically ill adult or pediatric patients transported by
      dedicated transport crews or tertiary-based specialists with other forms of
      transport personnel including referring house staff. All potentially relevant
      articles were retrieved in full and reviewed independently by 2 reviewers to
      determine eligibility for inclusion. Data were tabulated and results were
      summarized. RESULTS: Six cohort studies (n = 4534) were included. When patients
      of equal severity were assessed, only 1 study demonstrated an improvement in
      outcome at the receiving hospital (survival to 6 hours) when specialist personnel
      transported the patients. Methodological limitations and interstudy differences
      in participants and transport personnel precluded pooling of results.
      CONCLUSIONS: Current data are insufficient. The study designs used create
      opportunity for significant bias, preventing any useful inferences to be drawn.
      Further study is warranted.

PMID- 16616619
TI  - The evolution of intensive care unit performance assessment.
AB  - Intensive care units (ICUs) share the problems experienced by the health care
      system at large. Various approaches to define and manage the quality of care
      patients receive in the ICU have been proposed. Performance measurement involves
      the collection of data to evaluate an ICU's performance against itself (over
      time), other ICUs, or other appropriate benchmarks. Successful performance
      assessment requires the quantification of relevant indexes of performance.
      Although these indexes are increasingly being developed, it will be some time
      before widely recognized, validated systems are available.

PMID- 16616620
TI  - Clinical trial design--effect of prone positioning on clinical outcomes in
      infants and children with acute respiratory distress syndrome.
AB  - PURPOSE: This paper describes the methodology of a clinical trial of prone
      positioning in pediatric patients with acute lung injury (ALI). Nonrandomized
      studies suggest that prone positioning improves oxygenation in patients with
      ALI/acute respiratory distress syndrome without the risk of serious iatrogenic
      injury. It is not known if these improvements in oxygenation result in
      improvements in clinical outcomes. A clinical trial was needed to answer this
      question. MATERIALS AND METHODS: The pediatric prone study is a multicenter,
      randomized, noncrossover, controlled clinical trial. The trial is designed to
      test the hypothesis that at the end of 28 days, children with ALI treated with
      prone positioning will have more ventilator-free days than children treated with
      supine positioning. Secondary end points include the time to recovery of lung
      injury, organ failure-free days, functional outcome, adverse events, and
      mortality from all causes. Pediatric patients, 42 weeks postconceptual age to 18
      years of age, are enrolled within 48 hours of meeting ALI criteria. Patients
      randomized to the prone group are positioned prone within 4 hours of
      randomization and remain prone for 20 hours each day during the acute phase of
      their illness for a maximum of 7 days. Both groups are managed according to
      ventilator protocol, extubation readiness testing, and sedation protocols and
      hemodynamic, nutrition, and skin care guidelines. CONCLUSIONS: This paper
      describes the process, multidisciplinary input, and procedures used to support
      the design of the clinical trial, as well as the challenges faced by the clinical
      scientists during the conduct of the clinical trial.

PMID- 16616622
TI  - Controversies in sepsis clinical trials: proceedings of a meeting of the
      International Sepsis Forum, Lausanne, Switzerland, September 29, 2001.
AB  - Despite some recent success with clinical trials studying innovative therapies in
      sepsis, the field remains predominantly one of failure despite compounds with
      significant preclinical activity. Preclinical animal experimentation remains an
      important component of drug development, and a portfolio approach is recommended.
      Failure in animals is more likely to predict failure in humans; however, success
      in animals often does not predict success in humans. Because the signal with
      innovative therapy of sepsis is likely to be low, an oncology model clinical
      trial approach, in which studies start with a high-risk homogeneous population
      and look for a large treatment effect with smaller numbers of patients, is likely
      to be more relevant than the commonly used cardiology model, in which studies
      search for a small treatment effect using large, heterogeneous, low-risk
      populations. With certain rules in place, improvement in organ function may be a
      worthwhile alternative to mortality as a clinical end point. Once a therapy is
      approved, adopting less stringent but still appropriate criteria for the use of
      that therapy in clinical practice may be appropriate.

PMID- 16616623
TI  - Systemic inflammatory response syndrome and surgical stress in thoracic surgery.
AB  - PURPOSE: To evaluate the clinical usefulness of postoperative systemic
      inflammatory response syndrome (SIRS) as an index of surgical stress in patients
      undergoing thoracic surgery. METHODS: Forty-five consecutive patients who
      underwent thoracic surgery with thoracotomy were enrolled. The SIRS criteria were
      examined daily during the first 7 postoperative days. The serum interleukin-6 (IL
      6) level, operation time, intraoperative blood loss, amount of thoracic drainage,
      and C-reactive protein levels were also measured. RESULTS: Sixteen cases were
      categorized into the SIRS group, whereas 29 cases were categorized into the non
      SIRS group. Among the patients who underwent thoracic surgery, the physiological
      responses of the patients to the surgery, such as serum IL-6 levels and C
      reactive protein levels, were significantly higher in the SIRS group than in the
      non-SIRS group (P = .002 and .024, respectively). The serum IL-6 level on the
      first postoperative day was an independent factor associated with SIRS (95% CI
      1.002-1.041; P = .030). Furthermore, there was a correlation between the number
      of SIRS days and the duration of the postoperative hospital stay (r = 0.379, P =
      .012). CONCLUSIONS: Our results demonstrated that SIRS reflected the degree of
      surgical stress, especially thoracotomic procedures, through the IL-6 levels, and
      affected the postoperative hospital stay. Systemic inflammatory response syndrome
      can be useful for the postoperative management of patients undergoing thoracic
      surgery.

PMID- 16616625
TI  - Incidence, risk factors, and outcome of ventilator-associated pneumonia.
AB  - OBJECTIVE: The purpose of this study is to determine the incidence, risk factors,
      and outcome of ventilator-associated pneumonia (VAP). DESIGN: Prospective cohort.
      SETTING: Three hundred sixty-one intensive care units (ICUs) from 20 countries.
      PATIENTS AND PARTICIPANTS: Two thousand eight hundred ninety-seven patients
      mechanically ventilated for more than 12 hours. MEASUREMENTS AND RESULTS:
      Baseline demographic data, primary indication for mechanical ventilation, daily
      ventilator settings, multiple organ failure over the course of mechanical
      ventilation, and outcome were collected. Ventilator-associated pneumonia was
      present in 439 patients (15%). Patients with VAP were more likely to have chronic
      pulmonary obstructive disease, aspiration, sepsis, and acute respiratory distress
      syndrome. Mortality in patients with VAP was 38%. Factors associated with
      mortality were severity of illness, limited activity before the onset of
      mechanical ventilation and development of shock, acute renal failure, and
      worsening of hypoxemia during the period of mechanical ventilation. Case-control
      analysis showed no increased mortality in patients with VAP (38.1% vs 37.9%, P =
      .95) but prolonged duration of mechanical ventilation and ICU stay. CONCLUSION:
      In a large cohort of mechanically ventilated patients, VAP is more likely in
      patients with underlying lung disease (acute or chronic). Ventilator-associated
      pneumonia was associated with a significant increase in ICU length of stay but no
      increase in mortality.

PMID- 16616626
TI  - Epidemiology and prognostic factors of critically ill patients treated with
      hemodiafiltration.
AB  - PURPOSE: The objective of this study is to study the epidemiology, outcome, and
      prognostic factors of critically ill patients treated with continuous venovenous
      hemodiafiltration (CVVHDF). MATERIALS AND METHODS: Observational cohort was done
      in a French 16-bed intensive care unit (ICU) from a university-affiliated urban
      hospital. All patients requiring, in the opinion of the treating physician, the
      initiation of CVVHDF were included in the study. RESULTS: One hundred ninety
      seven patients with acute renal failure (ARF) treated with CVVHDF were studied.
      The incidence of ARF treated with CVVHDF was 5.9% in the ICU with a mortality
      rate of 71.6%. A multivariate analysis identified 3 independent factors
      associated with fatal outcome: mechanical ventilation, sepsis, and septic shock
      requiring vasoactive drug. In contrast, 2 independent factors predicted a
      favorable outcome: nonoliguric ARF and serum creatinine concentration higher than
      34 mg/L at CVVHDF initiation. A flowchart determined by the chi2 Automatic
      Interaction and Detection statistical method allowed for the identification of
      patients' subgroups with different mortality rates ranging from 25% to 100%.
      CONCLUSIONS: In our series, ARF treated with CVVHDF was associated with a high
      overall ICU mortality rate (71.6%). However, our prognostic flowchart identified
      patients with low mortality rates for which renal replacement therapy must be
      initiated with no discussion as soon as required.

PMID- 16616628
TI  - Diagnosis and treatment of relative adrenal insufficiency: confusing but at a
      higher level?

PMID- 16616627
TI  - Relative adrenal insufficiency in patients with septic shock; a close look to
      practice patterns.
AB  - PURPOSE: To assess patterns of practice in our institution specifically regarding
      corticosteroid deficiency diagnosis in patients with septic shock. METHODS:
      Consecutive adult patients with vasopressor-dependent septic shock admitted to
      the medical intensive care unit between January 2002 and September 2003 were
      studied. Relative adrenal insufficiency (RAI) was diagnosed by a random serum
      cortisol level <or=15 microg/dL or by a random cortisol level between 15 and 34
      microg/dL and an increase in response to cosyntropin stimulation test (250
      microg) <or=9 microg/dL. RESULTS: Ninety-two patients were included in the study.
      Mean (+/-SD) age was 59 +/- 18 years. Overall mortality was 53%. Relative adrenal
      insufficiency was suspected in 44 (48%) patients and confirmed in 25 (57%).
      Maximal doses of vasopressors were comparable between groups but more patients in
      whom AI was suspected were on phenylephrine and/or vasopressin and more were
      treated with activated protein C (P < .05). Diagnosis of RAI was confirmed by a
      low basal cortisol (<15 microg/dL) in 12 (48%) patients, whereas a diagnosis of
      RAI was made by a lack of response to the stimulation test in the rest.
      CONCLUSIONS: Relative adrenal insufficiency was diagnosed in half of the patients
      investigated. Patients with presumed RAI were more likely to be on phenylephrine
      or vasopressin infusions and treated with activated protein C and had a longer
      intensive care unit stay but no difference in intensive care unit survival.

PMID- 16616629
TI  - Monitoring of subcutaneous dalteparin in patients with renal insufficiency under
      intensive care: an observational study.
AB  - OBJECTIVE: The objective of this study was to investigate the pharmacodynamic
      parameters of dalteparin in patients with renal insufficiency under intensive
      care. MATERIALS AND METHODS: In this open, nonrandomized, nonblinded,
      prospective, single-dose observational study, 10 critically ill patients with
      renal insufficiency (mean creatinine clearance = 29.5 +/- 6.42 mL/min) were
      administered a single 5000-IU subcutaneous dose of dalteparin. RESULTS:
      Dalteparin blood levels were estimated indirectly over a 12-hour period by
      measuring anti-Xa activity and by performing a clotting assay known as the ATHU
      (AHEPA Thrombosis and Hemostasis Unit) test. Maximum anti-Xa activity (ie, 0.42
      +/- 0.13 IU/mL) was achieved 4 hours after administration (in 8 of 10 patients).
      Adequate anticoagulant activity was maintained throughout the 12-hour dosage
      interval in all study patients. However, at time 0 hour of the study, 36 hours
      after the administration of a previous dose of dalteparin, considerable anti-Xa
      activity (ie, 0.39 +/- 0.11 IU/mL) was measured in 6 patients. A good correlation
      was found between anti-Xa activity and the results of the ATHU test. CONCLUSIONS:
      The presence of medium/severe edema and the concurrent administration of 1 to 3
      inotropic drugs appear to contribute to a decrease in the rate of elimination of
      dalteparin, resulting in a greater-than-expected (as a result of decreased renal
      function) prolongation of its pharmacologic activity. We recommend that care be
      taken with repeated dosing of dalteparin in intensive care unit patients taking
      inotropic drugs until observed results can be confirmed.

PMID- 16616630
TI  - Multiple-organ effect of normobaric hyperoxia in neonatal rats.
AB  - PURPOSE: Prolonged exposure to normobaric hyperoxia (NH) is associated with blood
      leukocyte activation and sequestration in the lung. Whether NH-induced leukocyte
      activation and sequestration can affect extrapulmonary organs or blood cellular
      profile has not been systematically investigated. We studied simultaneous changes
      in blood cellular profile and pulmonary, renal, and intestinal histology during
      NH and after return to air breathing ("weaning"). MATERIALS AND METHODS: One-day
      old rats were exposed to 2 to 4 days of NH (FiO2 >0.98) or normoxia (FiO2 =
      0.21), with or without weaning. Pups were then euthanized and 100 microL of blood
      was collected (cardiac puncture) for differential white blood cells analysis (n =
      12 per group). The lungs, a piece of distal ileum, and the left kidney were
      removed for histologic evaluation. RESULTS: Both NH and weaning generated
      significant increases in blood neutrophil count, whereas lymphocyte population
      was significantly increased only after weaning (P < .05; analysis of variance
      with Bonferroni correction for multiple comparisons). Normobaric hyperoxia
      created mild increases in the renal tubular necrosis, dilation, regeneration, and
      interstitial inflammation. A significant increase in the intestinal serosal and
      submucosal vasodialation and vascularization occurred 1 day after weaning from 4
      days of NH (P < .001). These extrapulmonary events coincided with the development
      of histologic manifestations of pulmonary oxygen toxicity. CONCLUSIONS:
      Development of pulmonary oxygen toxicity in neonatal rats is associated with
      significant changes in differential leukocyte counts and histologic alterations
      in the kidney and ileum. We speculate that activation of circulating leukocytes
      and/or direct effect of NH may affect certain peripheral organs independently
      from the NH-induced pulmonary pathology.

PMID- 16616632
TI  - Investigation of altered heart rate variability, nonlinear properties of heart
      rate signals, and organ dysfunction longitudinally over time in intensive care
      unit patients.
AB  - PURPOSE: To investigate longitudinally over time heart rate dynamics and relation
      with mortality and organ dysfunction alterations in patients admitted to a
      multidisciplinary intensive care unit. METHODS: Data from 53 patients were used,
      with heart rate recorded from monitors and analyzed on a daily basis (every
      morning) for 600 seconds and sampling rate at 250 Hz, from admission to the
      intensive care unit until final discharge from the unit. Variance, which is a
      measure of heart rate variability; exponent alpha2; and approximate entropy
      (ApEn), which assess long-range correlations and periodicity within a signal,
      respectively; were measured and compared with every day Sequential Organ Failure
      Assessment Score (SOFA) and mortality. RESULTS: Nonsurvivors had lower ApEn mean
      (greater periodicity in their signals) and minimum values compared to survivors
      (0.53 +/- 0.25 vs 0.62 +/- 0.23, P = .04; 0.24 +/- 0.23 vs 0.48 +/- 0.23, P =
      .01, respectively). Patients in better conditions with SOFA of less than 7 (mean
      value) had higher variance and ApEn (more variable, less periodic signals) than
      those with SOFA of 7 or higher (0.47 +/- 0.51 vs 0.10 +/- 0.65, P < .001; 0.67 +/
      0.28 vs 0.49 +/- 0.24, P < .001, respectively). The alpha2 exponent and variance
      were correlated with length of stay (r = 0.55, P = .02, and r = 0.53, P = .02,
      respectively) and minimum ApEn with mortality (r = 0.41, P = .01). CONCLUSIONS:
      Loss of variability and increase in periodicity in heart rate of critically ill
      patients are linked with parallel deterioration of organ dysfunction and high
      mortality.

PMID- 16616634
TI  - Concepts for developing a collaborative in silico model of the acute inflammatory
      response using agent-based modeling.
AB  - The complexity of the acute inflammatory response (AIR) is, by now, generally
      recognized. The primary manifestation of this property has been the difficulty in
      translating the information derived from reductionist, basic science research
      into effective clinical treatment regimens for sepsis. However, the recognition
      of the "complexity" of the AIR is not without its pitfalls. Despite its
      limitations, reductionism remains the primary means of obtaining scientific
      information. Furthermore, a functional shortcoming of use of the term complex has
      been to make it equivalent to "essentially unsolvable." Therefore, a mechanism is
      needed to integrate the apparatus of reductionist analysis into a complex
      synthetic methodology that overcomes the current limitations of both. Toward this
      end, I propose a structure for a class of collaborative, community-wide in silico
      models that use the framework of agent-based modeling. Agent-based modeling is a
      type of mathematical modeling that focuses on the behaviors of the components of
      complex systems and is well suited for translating the results of basic science
      experiments. I will also introduce a preliminary version of a syntactical
      "grammar" that can potentially be used to facilitate the transfer of basic
      science data into computer code. It is hoped that when a mature version of this
      framework is implemented, the resulting models will provide a functional,
      synthetic data base on the AIR that could be used for directing research, testing
      hypotheses, teaching and training, and drug discovery/testing.

PMID- 16616636
TI  - Methemoglobinemia and acute hemolysis after tetracaine lozenge use.
AB  - Acquired methemoglobinemia is a rare but severe condition associated with
      oxidizing stressors, most notably medications. Although the symptoms can be life
      threatening, they usually respond promptly to exposure cessation and methylene
      blue injection. We describe the first case of methemoglobinemia associated with
      tetracaine lozenge use. A previously healthy 33-year-old man was admitted with
      fever, respiratory distress, cyanosis, and acute hemolysis. Physical findings and
      chest radiograph were normal. Low pulse oximetry readings contrasted with normal
      partial pressure of oxygen and calculated oxygen saturation. The methemoglobin
      level was 10.8%. The patient recovered with methylene blue injection and blood
      transfusions. He reported recent self-medication with tetracaine lozenges for a
      sore throat during a flu-like illness. No other cause of methemoglobinemia was
      found.

PMID- 16616637
TI  - Response to discussion by Dr Philip Hebert. Use of recombinant activated factor
      VIIa (FVIIa) in severe head injury.

PMID- 16616639
TI  - Re-evaluation of how artemisinins work in light of emerging evidence of in vitro
      resistance.
AB  - There are more than half a billion cases of malaria every year. Combinations of
      an artemisinin with other antimalarial drugs are now recommended treatments for
      Plasmodium falciparum malaria in most endemic areas. These treatment regimens act
      rapidly to relieve symptoms and effect cure. There is considerable controversy on
      how artemisinins work and over emerging indications of resistance to this class
      of antimalarial drugs. Several individual molecules have been proposed as targets
      for artemisinins, in addition to the idea that artemisinins might have many
      targets at the same time. Our suggestion that artemisinins inhibit the parasite
      encoded sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) PfATP6 has gained
      support from recent observations that a polymorphism in the gene encoding PfATP6
      is associated with in vitro resistance to artemether in field isolates of P.
      falciparum.

PMID- 16616640
TI  - Hormonal regulation of placental nitric oxide and pathogenesis of pre-eclampsia.
AB  - The placenta is central to foetal growth and development in mammalian pregnancy.
      Compromised placental function (as found in pre-eclampsia) often results in life
      threatening situations for both mother and foetus. The nitric-oxide (NO)
      signalling cascade is important for placental function, in particular for the
      development of the vascular network and for maintaining vascular tone. This
      pathway seems to be regulated by multiple hormonal signals. Emerging evidence
      suggests that pathogenic mechanisms that are involved in abnormal placental
      function target specific molecules, such as hormone receptors, that regulate NO
      release and have subsequent dramatic consequences. Here, we discuss the current
      knowledge of NO function in the placenta, its hormonal regulation in normal
      pregnancy and in the pathophysiology of pre-eclampsia, its potential pathogenic
      mechanisms and possible use as a therapeutic target.

PMID- 16616641
TI  - Unease on the role of glyoxalase 1 in high-anxiety-related behaviour.
AB  - Overexpression and silencing of glyoxalase 1 (Glo1) in brains of mice and
      behavioural analyses have suggested a link between Glo1 and anxiety, making Glo1
      a possible novel target for anxiolytic-drug development. However, this finding is
      discordant with others, and further research at metabolic level, particularly
      glycation of neuronal proteins by dicarbonyl substrates of Glo1, is required.
      Therefore, it remains to be established whether Glo1 is a risk marker or a risk
      factor of increased anxiety, how applicable the association between Glo1 and
      anxiety is and whether it can be translated into clinical diagnostic and
      therapeutic applications.

PMID- 16616642
TI  - Neospora caninum in wildlife.
AB  - Neosporosis, which is caused by the coccidian parasite Neospora caninum, is
      recognized as a major disease of domestic animals that causes high abortion rates
      in cattle and fatal neurological disease in dogs. A life cycle of N. caninum in
      wild animals (i.e. sylvatic) has long been suspected because neosporosis has been
      detected in several wildlife species. Recently, the transmission of N. caninum
      has been confirmed in coyotes and white-tailed deer. The newly confirmed wild
      hosts and other wild animals are probably involved in the sylvatic cycle of the
      parasite. Control measures for neosporosis could now become more complicated,
      given the participation of wildlife in the life cycle of N. caninum.

PMID- 16616643
TI  - Caring for patients with chronic heart failure: The trajectory model.
AB  - The purpose of this paper is to examine gaps in our understanding of the heart
      failure experience and describe the use of Trajectory of Chronic Illness Theory
      to bridge these gaps. New pharmacotherapeutic strategies have improved survival
      in heart failure, but research has consistently shown that clinical outcomes in
      these patients do not depend on physiologic variables alone. Psychological,
      behavioral, environmental, social and socioeconomic variables also contribute to
      a patient's ability to manage chronic illness. However, we have not yet
      identified the essential elements in helping patients engage in self-management
      and adhere to increasingly complex medical regimens. Theoretical models
      facilitate disciplinary integration, providing a comprehensive and cohesive
      foundation for building better science. The Trajectory of Chronic Illness Theory
      is particularly salient for heart failure because of its emphasis on patients'
      ability to manage a chronic illness. By using theory to explore gaps in our
      understanding of the heart failure experience, investigators may be able to
      develop more targeted interventions to help patients manage heart failure.

PMID- 16616644
TI  - 6th Annual Spring Meeting of the Working Group on Cardiovascular Nursing of the
      European Society of Cardiology and the Spring Meeting of the Norwegian National
      Society of Cardiovascular Nurses, Bergen, Norway, 5-6 May 2006. Abstracts.

PMID- 16616645
TI  - Role of inducible costimulator in the development of lupus in MRL/lpr mice.
AB  - Inducible costimulator (ICOS) is a costimulatory molecule expressed in activated
      T cells and plays an important role in T-cell-dependent immune responses. We
      investigated the role of ICOS in the development of autoimmune diseases in
      MRL/Mpj-lpr/lpr (MRL/lpr) mice. ICOS was expressed on CD4(+) T cells from adult
      MRL/lpr mice. ICOS-deficient MRL/lpr mice showed mild lymphoadenopathy and a
      decreased memory type CD4(+) T cells in the spleen. The anti-dsDNA antibody
      levels were decreased. CD4(+) T cells from ICOS-deficient MRL/lpr mice showed
      less of a bias to Th1 and an enhanced production of IL-4 in response to anti-CD3
      antibody in comparison to those from wild-type MRL/lpr mice. Although ICOS
      deficiency abrogated renal vasculitis completely, the severity of
      glomerulonephritis was not altered. ICOS is considered to play a role in CD4(+) T
      cell activation, autoantibody production, and renal vasculitis. However, it is
      not essentially required in the development of glomerulonephritis.

PMID- 16616646
TI  - Evaluation of mitral valve area by the proximal isovelocity surface area method
      in mitral stenosis: could it be simplified?
AB  - AIM: One limitation for a wider use of the proximal isovelocity surface area
      method (PISA) for the evaluation of the mitral valve area (MVA) in patients with
      mitral stenosis (MS) is the requirement of an angle correction factor (angle
      alpha between the mitral leaflets) which cannot be obtained using the machine's
      built-in software and requires a manual measurement. The aim of the present study
      was to evaluate if the use of a fixed angle could provide an acceptable MVA
      estimation. METHODS AND RESULTS: In 48 patients (53 +/- 14 years, 75% female and
      32% atrial fibrillation), MVA was prospectively measured by planimetry (MVA(2D))
      and PISA (PISA(mes)). The angle alpha was manually measured on paper prints using
      a protractor. MVA(2D) was 1.38 +/- 0.56 cm(2) [0.5-2.40]. PISA(mes) (alpha = 104
      +/- 13 degrees inter-quartiles 90-115) was 1.34 +/- 0.64 cm(2) [0.31-2.95] and
      did not differ from and correlated well with MVA(2D) (P = 0.25; r = 0.93, P <
      0.0001). MVA estimated using the PISA method and a fixed angle value from 90 to
      110 (MVA(alpha)(=90) to MVA(alpha)(=110)) progressively increased from 1.20 +/-
      0.66 to 1.48 +/- 0.81 cm(2). Only MVA(alpha)(=100) (1.34 +/- 0.74 cm(2)) did not
      differ from and correlated well with both MVA(2D) and PISA(mes) (both P > 0.35
      and r > 0.90, P < 0.0001). CONCLUSION: The angle formed by the mitral leaflet
      only slightly changes in between patients and use of a fixed angle value of 100
      degrees provides an accurate estimation of the MVA by the PISA method in patients
      with MS. This simplification would facilitate and extend the use of the PISA as
      an additional method for the assessment of MS severity in routine practice.

PMID- 16616647
TI  - Frontoparietal activation during delayed visuospatial recall in patients with
      epilepsy due to hippocampal sclerosis.
AB  - We hypothesized that brain activation during encoding and retrieval of visual
      material differed between epilepsy patients with hippocampal sclerosis (HS) and
      healthy controls. Eleven patients with epilepsy and HS and nine age- and
      education-matched control subjects were tested during functional MRI recording. A
      three-block design for visuospatial memory encoding and retrieval and an
      interference interval longer than 1 minute without memory tasks were used. All
      subjects revealed parietal, occipital, and prefrontal activation patterns during
      encoding. Interference revealed parietal more than occipital activation, whereas
      retrieval revealed asymmetrical frontal and parietal activation. Patients
      demonstrated a relative increase in occipitoparietal versus frontal cortical
      activation as compared with controls. Memory performance did not differ between
      patients and controls. The increased activation in occipitoparietal versus
      frontal areas in the patients suggests cortical reorganization of visuospatial
      recognition memory in epilepsy patients with HS. The study is limited by other
      factors that may contribute to the results, for example, antiepileptic drugs,
      effects of greater cognitive effort allocated in patients than controls, and
      possibly subclinical epileptic activity. However, normal visuospatial memory
      performance in our patients with HS suggests successful network plasticity.

PMID- 16616648
TI  - Prognosis of seizure recurrence after stopping antiepileptic drugs in seizure
      free patients: A long-term population-based study of childhood-onset epilepsy.
AB  - The long-term outcome with respect to seizure relapse after planned
      discontinuation of antiepileptic drugs (AEDs) in seizure-free patients is not
      well known. Relapse and its treatment outcome were evaluated in a longitudinal
      population-based study of 148 patients from the onset of their epilepsy to an
      average follow-up of 37 years. During the study, AEDs were completely
      discontinued by 90 patients; 58 patients remained on medication. Seizure relapse
      after AED discontinuation was observed in 33 (37%) of 90 patients at an average
      follow-up of 32 years. Among 8 of the 33 patients who elected to restart AEDs, 2
      achieved 5-year terminal remission (5YTR), but only 10-19 years after restarting
      treatment. The other 6 patients never achieved 5YTR, and 2 of the 6 never entered
      a 5-year remission period during follow-up. Factors associated with failure to
      reach 5YTR after treatment of relapse were symptomatic etiology and localization
      related epilepsy. In conclusion, drug discontinuation after seizure freedom
      results in relapse in one-third of patients. Reinstitution of a medication that
      worked for years fails to achieve control in one of four patients. These risks
      need to be considered, although there is no evidence that discontinuation is
      responsible for the poor prognosis for treatment of seizure recurrence.

PMID- 16616649
TI  - Is supplemental oxygen necessary?

PMID- 16616650
TI  - Effect of lung ventilation with 50% oxygen in air or nitrous oxide versus 100%
      oxygen on oxygenation index after cardiopulmonary bypass.
AB  - OBJECTIVE: This study was designed to assess the use of 100% oxygen or 50% oxygen
      in air or nitrous oxide after cardiopulmonary bypass (CPB) on atelectasis, as
      evidenced by the oxygenation index (PaO2/F(I)O2), after coronary artery bypass
      graft (CABG) surgery. DESIGN: Prospective, randomized clinical study. SETTING:
      University teaching hospital. PARTICIPANT: Thirty-six adult patients undergoing
      CABG surgery. INTERVENTIONS: Patients either received 50% O2 in air (50% O2
      group), 50% O2 in N2O (50% N2O group), or 100% O2 (100% O2 group) after CPB.
      MEASUREMENTS AND MAIN RESULTS: Apart from demographic and perioperative clinical
      data, extubation time, mediastinal drainage, and pulmonary complications were
      also recorded. After CPB, arterial blood gases done at various time points until
      3 hours postextubation and oxygenation index were calculated. No significant
      differences were noted in demographic and perioperative data except preoperative
      hemoglobin and fluid use. Significant deterioration in arterial oxygenation was
      noted in the 100% O2 group from the baseline value, whereas significant
      improvement was seen in the 50% O2 group at 4 time points from baseline value and
      at all time points from the 100% O2 group. After initial deterioration in
      oxygenation, no further change was evident in the 50% N2O group. Furthermore,
      there was a greater increase in the oxygenation index as compared with the 100%
      O2 group. Time to extubation was also longer in the 100% O2 group than the 50% O2
      group. CONCLUSION: Significant deterioration in arterial oxygenation and an
      increase in the extubation time occurred with the use of 100% O2 after CPB,
      whereas better oxygenation was evident with the use of 50% O2 in air.

PMID- 16616651
TI  - Predictive factors of hemodynamic collapse after coronary artery bypass grafting:
      a case-control study.
AB  - OBJECTIVE: Sudden hemodynamic collapse after coronary artery bypass graft (CABG)
      surgery is a complication with high morbidity and mortality. The aim of this
      study was to explore factors possibly predictive of this major complication.
      DESIGN: Retrospective case-control study. SETTING: University hospital,
      department of cardiothoracic surgery. PARTICIPANTS: Between 1988 and 1999, of
      8,807 CABG patients, a total of 76 (0.9%) suffered hemodynamic collapse after
      CABG surgery unrelated to pericardial tamponade or bleeding. Preoperatively
      matched patients (by age, sex, New York Heart Association classification, number
      of diseased vessels, left ventricular ejection fraction, and diabetes) served as
      a control group (n = 76). INTERVENTIONS: Patients with sudden cardiovascular
      collapse underwent emergency reopening of the sternotomy and open cardiac massage
      (OCM group). Several pre-, intra-, and postoperative variables were compared, and
      significant parameters in match-pair analysis were further tested with regression
      techniques. MEASUREMENTS AND MAIN RESULTS: Of the 76 OCMs, 57 (75%) occurred
      during the first 5 postoperative hours. In-hospital mortality was 46% (35 of 76)
      versus 0% in controls; 5-year survival was 49% versus 95%. In the OCM group,
      cardiopulmonary bypass (CPB) time was significantly prolonged (p = 0.0024), and
      cardiac index (p = 0.05) and the first acid-base values after CPB were lower (pH,
      p = 0.0057; BE, p = 0.0014). Postoperative myocardial ischemia appeared in 33% of
      patients in the OCM group and in 8% of controls (p < 0.0001). OCM-group patients
      more frequently required postoperative inotropic (epinephrine, p = 0.0002) and
      mechanical support (intra-aortic balloon pump, p = 0.005). Regression analysis
      revealed a correlation between cardiopulmonary resuscitation risk and low cardiac
      index, postoperative ischemia, and low pH level. CONCLUSION: Inadequate tissue
      perfusion, postoperative myocardial ischemia, and increased need for inotropic
      and mechanical support preceded hemodynamic collapse. Interventions to improve
      tissue perfusion and to prevent and treat myocardial ischemia may result in a
      more favorable outcome.

PMID- 16616652
TI  - The degree of atherosclerosis in the descending aorta does not predict poor in
      hospital outcome after surgery requiring cardiopulmonary bypass.
AB  - OBJECTIVE: This study examined if the degree of atherosclerosis in the descending
      aorta is an independent predictor of poor in-hospital outcome for patients
      presenting for surgery involving cardiopulmonary bypass. DESIGN: The degree of
      atherosclerosis of the descending aorta was retrospectively reviewed in patients
      presenting for surgical procedures involving cardiopulmonary bypass from January
      1, 2000, to December 31, 2003. Preoperative risk factors and in-hospital
      postoperative outcome parameters were obtained. SETTING: University teaching
      hospital. PARTICIPANTS: There were 310 consecutive patients enrolled in the
      study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred forty
      seven patients had coronary artery bypass grafting with or without valvular
      surgery, and 63 patients had isolated valvular surgery. The degree of
      atherosclerosis was rated as normal in 86 (28%), mild in 106 (34%), moderate in
      69 (22%), and severe in 49 (16%) patients. Adjusting only for the degree of
      atherosclerosis, the total intensive care unit (ICU) time and the number of
      deaths were significantly higher in those patients with severe disease.
      Multivariable models adjusting for patients' risk factors showed a significant
      influence of atherosclerosis on total ICU time but not on other outcomes. The
      strongest predictor of poor outcome was a history of previous stroke (cerebral
      vascular accident). Other significant factors predicting poor outcome included
      previous coronary artery bypass surgery, a history of congestive heart failure, a
      history of dialysis, advanced age, and female sex. CONCLUSIONS: The degree of
      atherosclerosis in the descending aorta is not an independent predictor of poor
      in-hospital outcome after surgery involving cardiopulmonary bypass.

PMID- 16616653
TI  - Retrograde autologous priming of the cardiopulmonary bypass circuit: safety and
      impact on postoperative outcomes.
AB  - OBJECTIVES: Retrograde autologous priming (RAP) is a blood conservation technique
      used to limit the severity of hemodilution during cardiopulmonary bypass and
      reduce perioperative transfusions. The aim of this investigation was to examine
      the safety of RAP and to determine the effect of RAP on adverse outcomes after
      cardiac surgery. DESIGN: Retrospective cohort study. SETTING: University
      hospital. PARTICIPANTS: Five hundred fifty-nine undergoing cardiopulmonary
      bypass. INTERVENTIONS: Data were retrospectively collected on 2 cohorts of adult
      cardiac surgical patients operated on by a single surgeon. In the RAP group (n =
      256), outcome data were analyzed on all subjects over a 2-year period during
      which RAP was used routinely. This group was compared with a similar cohort of
      patients undergoing cardiopulmonary bypass over a 2-year period immediately
      before the introduction of RAP into the clinical practice (no-RAP group, n =
      287). MEASUREMENTS AND MAIN RESULTS: In-hospital mortality was not significantly
      different between the RAP group (2.7%) and the no-RAP group (3.8%, p = 0.636).
      The incidence of postoperative cardiac arrest was significantly less in the RAP
      group (1 patient) compared to the no-RAP group (9 patients, p = 0.040). There
      were no differences between the 2 groups in the incidence of several other
      postoperative complications, including postoperative delirium (1.6% RAP v 3.1% no
      RAP), heart block (1.6% RAP v 4.2% no RAP), atrial fibrillation (19.1% RAP v
      22.7% no RAP), and requiring postoperative ventilation >24 hours (2.7% RAP v 5.2%
      no RAP). CONCLUSIONS: The authors observed no evidence of any increase in adverse
      events in the RAP group of this retrospective cohort study, but they did observe
      a decrease in the incidence of postoperative cardiac arrest in the RAP group.
      These findings suggest that RAP is a safe technique and may have a beneficial
      effect on postoperative outcomes.

PMID- 16616654
TI  - Phosphodiesterase III inhibition affects platelet-monocyte aggregate formation
      depending on the axis of stimulation.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of the
      phosphodiesterase (PDE) type 3 inhibitor milrinone on the adhesion of platelets
      to monocytes in vitro. DESIGN: Prospective study. SETTING: University
      experimental laboratory. PARTICIPANTS: Ten healthy volunteers. INTERVENTIONS:
      Whole blood was incubated with 1, 10, or 100 micromol/L of milrinone. After
      stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or adenosine-5
      diphosphate (ADP), platelet-monocyte adhesion and CD11b, PSGL-1, GPIIb/IIIa, and
      P-selectin expression were measured by flow cytometry. MEASUREMENTS AND RESULTS:
      The formation of platelet-monocyte conjugates after PDE3 inhibition depended on
      the type of stimulation. In unstimulated and FMLP-stimulated blood platelet
      monocytes, aggregation was enhanced by increasing concentrations of milrinone.
      This augmentation was accompanied by a rise in P-selectin expression in
      platelets. In ADP-stimulated blood the number of platelet-monocyte aggregates
      decreased with increasing concentrations of milrinone. Concurrent with the
      reported antiinflammatory properties of PDE-inhibition, an inhibition of CD11b
      expression was found in monocytes after stimulation with FMLP. In contrast, in
      unstimulated samples lower concentrations of milrinone caused an increase in
      CD11b. CONCLUSIONS: These findings suggest that the effects of PDE3 inhibition on
      platelets and monocytes are modified by the type of stimulation and only
      partially suppress the inflammatory response of platelets and monocytes. The
      increase in platelet-monocyte conjugates in unstimulated and FMLP-stimulated
      blood suggested that PDE3 inhibition may also trigger proinflammatory reactions.

PMID- 16616655
TI  - Impact of vasopressin on hemodynamic and metabolic function in the decompensatory
      phase of hemorrhagic shock.
AB  - OBJECTIVES: To explore how the potent vasoconstrictive features of vasopressin
      impact the rate of cardiovascular collapse and metabolic derangements associated
      with prolonged hemorrhagic shock. DESIGN: A prospective randomized trial.
      SETTING: University hospital-based animal laboratory. PARTICIPANTS: Sixteen
      swine. INTERVENTIONS: Swine were bled in an isobaric fashion to achieve a linear
      decrease in the mean arterial blood pressure to 40 mmHg. The mean arterial blood
      pressure was then maintained at 40 mmHg until the onset of cardiovascular
      decompensation, defined as the need to reinfuse shed blood to maintain the blood
      pressure at 40 mmHg. Once at the onset of cardiovascular decompensation, animals
      were randomly assigned to 2 resuscitation groups: the crystalloid group received
      lactated Ringer's solution and the vasopressin group received lactated Ringer's
      solution and arginine vasopressin. Resuscitation consisted of infusing lactated
      Ringer's solution with and without vasopressin (0.05 U/kg/min) to maintain a
      blood pressure of 70 mmHg for 60 minutes. MEASUREMENTS AND MAIN RESULTS: The rate
      of crystalloid infusion was compared between groups using an unpaired 2-tailed t
      test. Metabolic and hemodynamic parameters between groups over time were compared
      with a repeated measures analysis of variance. Vasopressin decreased the rate of
      crystalloid infusion during resuscitation by 50%. During resuscitation, the
      cardiac index in the crystalloid group was restored to near baseline levels and
      was decreased to near half of baseline levels in the vasopressin group. Animals
      in the vasopressin group developed a lactic acidemia, but animals in the
      crystalloid group revealed no change from baseline in the arterial pH and a
      slight decrease in the plasma lactate. CONCLUSIONS: Administration of vasopressin
      used as an adjunct to maintain blood pressure in the decompensatory phase of
      hemorrhagic shock slows cardiovascular collapse, but has an adverse effect on
      metabolic and hemodynamic function. Further investigation is warranted to clarify
      the role of vasopressin in the delayed management of severe hemorrhagic shock.

PMID- 16616656
TI  - Comparison of systemic and renal effects of dopexamine and dopamine in
      norepinephrine-treated septic shock.
AB  - OBJECTIVES: Vasopressor-induced vasoconstriction may compromise renal and
      splanchnic blood flow in patients with septic shock, resulting in secondary organ
      failures. The authors compared the effects of the vasodilatatory agent dopexamine
      against renal-dose dopamine and placebo in patients with norepinephrine therapy
      and septic shock, using 24-hour serum creatinine clearance (C(crea)) as a major
      endpoint. The primary hypothesis to be tested was that dopexamine is more
      effective than dopamine and that dopamine shows better effects than placebo
      regarding organ failures and C(crea). DESIGN: A prospective, randomized,
      controlled, double-blinded study. SETTING: Intensive care unit in a tertiary care
      university hospital. PARTICIPANTS: Sixty-one patients with septic shock defined
      according to established criteria. INTERVENTIONS: Patients received either
      dopexamine (2 microg/kg/min, n = 20), dopamine (3 microg/kg/min, n = 21), or
      placebo (n = 20). RESULTS: The trial groups were similar in terms of baseline
      characteristics. The authors found no significant differences among the
      dopexamine, dopamine, and placebo groups with regard to a comprehensive number of
      renal function parameters including C(crea) and organ-failure scores. There was a
      significant increase in heart rate after dopexamine infusion; other hemodynamic
      parameters remained unchanged in the dopexamine group. In a post hoc analysis
      that included only patients with renal impairment at study inclusion (n = 28),
      patients who received dopamine showed significant improvements in C(crea) when
      compared with placebo. Dopexamine was not effective in this subgroup.
      CONCLUSIONS: Dopexamine is no more effective than dopamine or placebo regarding
      renal function in patients with septic shock requiring norepinephrine. Both
      therapies do not influence organ-failure scores.

PMID- 16616657
TI  - Fenoldopam inhibits nuclear translocation of nuclear factor kappa B in a rat
      model of surgical ischemic acute renal failure.
AB  - OBJECTIVE: Vasoactive compounds are known to modulate gene transcription,
      including nuclear factor kappa B (NF-kappaB), in renal tissues, but the molecular
      effects of fenoldopam in this setting are not known. The authors used a rat model
      of surgical acute ischemic nephropathy to test the hypothesis that fenoldopam
      attenuates ischemia/reperfusion (I/R)-induced NF-kappaB-mediated inflammation.
      DESIGN: Prospective, single-blind, randomized, controlled animal study. SETTING:
      Academic Department of Anesthesiology laboratory. SUBJECTS: Twenty-four male
      Sprague-Dawley rats. INTERVENTIONS: Rats were anesthetized by intraperitoneal
      administration of 50 mg/kg of urethane and randomly allocated into 4 groups (n =
      6 each): sham operation, sham operation with infusion of 0.1 microg/kg/min of
      fenoldopam, unilateral renal ischemia (1 hour, left renal artery cross-clamping)
      followed by 4 hours of reperfusion, and unilateral renal I/R with fenoldopam
      infusion. MEASUREMENTS AND MAIN RESULTS: Kidney samples were used to measure NF
      kappaB DNA-binding activity with an electrophoretic mobility shift assay. NF
      kappaB signaling-dependent gene transcription was assessed with microarray
      analysis, and validated with reverse transcriptase polymerase chain reaction (RT
      PCR). Expression of insulin-like growth factor-1 and nitric oxide synthetase-3
      messenger RNA (not included in the array) was studied with RT-PCR. NF-kappaB DNA
      binding activity was significantly higher (p < 0.001) after I/R injury. Of the 96
      genes analyzed, 75 were induced and another 8 were suppressed completely (2-fold
      or greater change v control) after I/R. Treatment with fenoldopam prevented
      activation of NF-kappaB DNA binding activity (p < 0.001) and attenuated 72 of 75
      I/R-induced genes and 3 of 8 I/R-suppressed genes. CONCLUSION: Data from this rat
      model of renal I/R suggest that the mechanism by which fenoldopam attenuates I/R
      induced inflammation appears to involve inhibition of NF-kappaB translocation and
      signal transduction.

PMID- 16616658
TI  - Influence of groin incision, duration of ischemia, and prostaglandin E1 on
      ischemia-reperfusion injury of the lower limb.
AB  - OBJECTIVE: The influences of groin incision, duration of ischemia, and the
      effects of prostaglandin E1 (PGE1) on ischemia-reperfusion (I/R) injury of the
      hind limb in rabbits were evaluated. DESIGN: A prospective study. SETTING:
      Laboratory. PARTICIPANTS: In 64 rabbits, bilateral hind limb ischemia was induced
      by occlusion of the abdominal aorta. Volume changes, neuromuscular function of
      the hind limb, and creatine kinase (CK) release were measured as variables of
      tissue injury. INTERVENTIONS: Eight rabbits served as untreated controls (CON).
      In 2 groups (each n = 14), 3 hours of ischemia were followed by 3 hours of
      reperfusion (I/R). In 2 different groups (each n = 14), 45 minutes of ischemia
      were followed by 2 hours of reperfusion. To determine effects of PGE1, 1 I/R
      group of each ischemia duration was treated intravenously with 80 ng/kg/min of
      PGE1 starting 30 minutes after the onset of ischemia (I/R-PGE1). To determine
      effects of groin incision on edema formation, volume changes were determined in
      the "operated" right (CON-R, 3h-R, 3h-PGE1-R and 45 min-R, 45 min-PGE1-R) or in
      the "nonoperated" left hind limb (CON-L, 3h-L, 3h-PGE1-L and 45 min-L, 45 min
      PGE1-L), representing a subgroup analysis. MEASUREMENTS AND MAIN RESULTS: Volume
      changes after I/R occurred only in operated legs after ischemia (3h-R: 2.3 +/-
      0.3 mL, p < 0.0001 v CON-R and 3h-L; 45 min-R: 0.8 +/- 0.2 mL, p < 0.01 v 45 min
      L). PGE1 reduced edema formation in the operated legs (3h-PGE1-R: 1.0 +/- 0.4 mL,
      p < 0.0001 v 3h-R; 45 min-PGE1-R: 0.5 +/- 0.3 mL, p = 1.0 v 45 min-R). Groin
      incision without I/R had no effect on edema formation (CON-R: -0.13 +/- 0.17 mL
      of baseline). The increase of CK release from 616 +/- 584 U/L in controls to
      5,921 +/- 2,156 U/L after 3 hours of ischemia (p < 0.001) was attenuated by
      treatment with PGE1 (3,732 +/- 2,653, p < 0.05 v I/R). Forty-five minutes of
      ischemia did not lead to cellular damage as measured by CK release (I/R: 606 +/-
      364 U/L). Recovery of neuromuscular function was not affected by PGE1.
      CONCLUSION: Development of edema during I/R depends on groin incision of the hind
      limb and on the duration of ischemia. The I/R injury is attenuated by PGE1
      treatment, in terms of reduced edema formation and CK release, but not in terms
      of neuromuscular function.

PMID- 16616659
TI  - Arterial-to-end-tidal carbon dioxide tension difference in children with
      congenital heart disease.
AB  - OBJECTIVES: This study estimated the arterial-to-end-tidal carbon dioxide tension
      difference (deltaPaCO2-PE'CO2) in children with congenital heart disease;
      evaluated whether hyperventilation can reduce this difference; and analyzed the
      relationship between the difference and the oxygen saturation (SaO2) and
      hemoglobin level. DESIGN: Prospective clinical study. SETTING: Tertiary health
      care center. PARTICIPANTS: One hundred patients scheduled for correction of their
      underlying cardiac defect with either right-to-left or left-to-right intracardiac
      shunts were divided into 4 groups (n = 25 each): (1) N1, cyanotic with severe
      pulmonary artery hypertension; (2) N2, cyanotic with normal or decreased
      pulmonary artery pressure (PAP); (3) N3, acyanotic with normal or mild increases
      in PAP and severe increases in pulmonary blood flow (PBF); and (4) N4, acyanotic
      with normal PAP and normal or mild increase in PBF. INTERVENTIONS: All the
      patients received the same anesthetic regimen. The initial settings for tidal
      volume, respiratory rate, and inspiratory-to-expiratory (I:E) ratio were 10
      mL/kg, 15 to 30 breath/min, and inspired time 40% of the total respiratory period
      with a 10% end-inspiratory pause. After the measurement of oxygen saturation,
      PO2, Hb, and deltaPaCO2-PE'CO2, all the children were hyperventilated (tidal
      volume: 14-15 mL/kg, respiratory rate: 5-6 breaths/min more than the initial
      rate, I:E ratio: same) to observe its effects on the deltaPaCO2-PE'CO2.
      MEASUREMENTS AND RESULTS: The deltaPaCO2-PE'CO2, when predicted from the oxygen
      saturation, hemoglobin concentration, and PaO2, was found to be greater than the
      observed value in the first 3 groups (p < 0.001); whereas in group N4 these 2
      values were comparable. It was also found that the gradient was higher when there
      was a decrease in SaO2 and an increase in the hemoglobin level. After
      hyperventilation, in groups N1 and N3, deltaPaCO2-PE'CO2 was decreased when
      compared with their baseline values; this reduction was not as much as predicted
      (p = 0.363 and 0.236, respectively). However, in groups N2 and N4
      posthyperventilation, the deltaPaCO2-PE'27 CO2 was decreased significantly below
      their baseline measurements. These decreases were as much predicted. CONCLUSION:
      The deltaPaCO2-end-tidal carbon dioxide (PE'CO2) can be increased both in
      cyanotic and acyanotic children. Increased PAP is as important as increased PBF
      or right-to-left shunting in producing disorders in carbon dioxide homeostasis.
      Hyperventilation is of little use in reducing deltaPaCO2-PE'CO2 in children with
      high PAPs and pulmonary hyperperfusion.

PMID- 16616660
TI  - Anesthesia for percutaneous transcatheter closure of perimembranous ventricular
      septal defect.
AB  - OBJECTIVE: To review the anesthetic management for percutaneous transcatheter
      closure of perimembranous ventricular septal defect (VSD) with an Amplatzer
      asymmetric occluder device and to highlight the hemodynamic effects and potential
      complications associated with its delivery. DESIGN: Retrospective review of
      prospectively collected data. SETTING: University-affiliated teaching hospital.
      PARTICIPANTS: Nine consecutive children undergoing elective percutaneous
      transcatheter closure of perimembranous VSD. INTERVENTIONS: General anesthesia
      with sevoflurane for cardiac catheterization and percutaneous transcatheter
      device placement. MEASUREMENTS AND MAIN RESULTS: Ten anesthetics were delivered
      in 9 children ages 23 to 65 months with perimembranous VSD for attempted
      placement of an Amplatzer asymmetric device. The device was successfully placed
      in 7 patients. In 1 patient the device embolized to the right femoral artery, and
      was retrieved with a bioptome. Fluoroscopy time (59.8 +/- 17.24 min) was
      prolonged compared to that in other studies of placement of this device. All
      patients had episodes of arrhythmia and hemodynamic disturbance. Arrhythmias
      ranged from atrial or ventricular ectopic events to various degrees of
      atrioventricular block. Complete heart block occurred during the procedure in 1
      patient and after the procedure in another patient. Hypotensive episodes occurred
      in 7 patients, and were attributed to arrhythmias in 5 patients and hypovolemia
      in 2 patients. Two patients were given blood transfusions after the procedure
      because they had signs of hypovolemia and a greater than 10% decrease in
      hemoglobin levels. CONCLUSIONS: Anesthesia for perimembranous VSD occluder
      placement is associated with hemodynamic instability, arrhythmias, prolonged
      procedure times, and inevitable and sometimes substantial blood loss.

PMID- 16616661
TI  - Sevoflurane alters right ventricular performance but not pulmonary vascular
      resistance in acutely instrumented anesthetized pigs.
AB  - OBJECTIVE: Although the effects of halogenated agents on both normal and diseased
      left ventricles have been widely studied, the influence of these anesthetic
      agents on right ventricular (RV) performance remains less well characterized.
      This study was undertaken to examine the effects of 2 different concentrations of
      sevoflurane on RV function, and coronary and pulmonary hemodynamics in acutely
      instrumented anesthetized pigs. DESIGN: Prospective experimental study. SETTING:
      Laboratory of experimental research in a university teaching hospital. SUBJECTS:
      Anesthetized pigs. INTERVENTIONS: Regional RV function in 10 pigs was determined
      from pressure segment length loop analysis, global RV function from stroke work
      versus end-diastolic pressure relation, right coronary blood flow, and pulmonary
      vascular resistance (PVR), without and then with 2.6% (minimum alveolar
      concentration [MAC]) and 3.9 % (1.5 MAC) end-tidal sevoflurane concentrations.
      MAIN RESULTS: Sevoflurane preserved inflow systolic shortening and RV regional
      external work, but significantly depressed outflow systolic shortening (p <
      0.05). Global RV stroke work was depressed to 72% +/- 12% and 61% +/- 10% of
      baseline value, respectively, with 1 and 1.5 MAC of sevoflurane (p < 0.05), but
      without alteration of PVR. Right coronary blood flow decreased dose dependently.
      CONCLUSIONS: Sevoflurane causes significant depression of global RV function
      associated with a qualitatively different effect on inflow and outflow tracts,
      without any modification of PVR.

PMID- 16616662
TI  - A randomized, double-blind, placebo-controlled study assessing the anti
      inflammatory effects of ketamine in cardiac surgical patients.
AB  - OBJECTIVE: To determine whether ketamine administration affects markers of
      inflammation in cardiac surgery with cardiopulmonary bypass (CPB) and to
      investigate differences between 2 low-dose ketamine regimens. DESIGN:
      Prospective, randomized, placebo-controlled trial. SETTING: Single-center
      university hospital. PARTICIPANTS: Patients undergoing cardiac surgery with CPB.
      INTERVENTION: Patients (n = 50) were randomized to 1 of 3 groups: ketamine, 0.25
      mg/kg (n = 15); ketamine, 0.5 mg/kg (n = 18);or placebo (n = 17) in a double
      blind manner at the time of induction of general anesthesia. MEASUREMENTS AND
      MAIN RESULTS: Serum C-reactive protein (CRP) and interleukin (IL)-6, IL-8, and IL
      10 were measured at baseline, on intensive care unit (ICU) arrival, and on the
      first postoperative day (POD 1). Both ketamine doses decreased the serum IL-6
      response at ICU arrival and POD 1 compared with placebo (p < 0.05). CRP was lower
      in the 0.5-mg/kg group than placebo on POD 1 (p = 0.003). IL-10 was lower in the
      ketamine groups (p = 0.01) at POD 1 compared with placebo; IL-8 levels were not
      affected by ketamine. Mean arterial pressure and systemic vascular resistance
      were higher at the end of surgery, arrival in the ICU, and POD 1 in the ketamine
      groups (p < 0.05). CONCLUSION: Low-dose ketamine (0.5 mg/kg) attenuates increases
      in CRP, IL-6, and IL-10 while decreasing vasodilatation after CPB.

PMID- 16616663
TI  - Difficulty assessing endotracheal tube placement in a patient with undiagnosed
      iatrogenic tracheoesophageal fistula.

PMID- 16616664
TI  - Bilateral vocal cord paralysis after lung cancer surgery with a double-lumen
      endotracheal tube: a life-threatening complication.

PMID- 16616665
TI  - Bronchial stenting through a ProSeal laryngeal mask airway.

PMID- 16616666
TI  - Life-saving detection of right hemothorax by transesophageal echocardiography
      after femorofemoral bypass.

PMID- 16616667
TI  - Very early intraoperative cardiac thromboembolism during liver transplantation.

PMID- 16616668
TI  - Pulmonary embolism: an uncommon cause of dyspnea after heart transplantation.

PMID- 16616669
TI  - Congenital lobar emphysema associated with congenital heart disease.

PMID- 16616670
TI  - An undiagnosed, massive pericardial effusion with a swinging heart.

PMID- 16616671
TI  - Delayed pericardial tamponade following transthoracic hiatal hernia repair.

PMID- 16616672
TI  - Left ventricle perforation during endovascular repair of an infrarenal aortic
      aneurysm.

PMID- 16616673
TI  - Influence of statins on perioperative outcomes.

PMID- 16616674
TI  - Case 2-2006: Catastrophic cardiovascular collapse during carotid endarterectomy.

PMID- 16616675
TI  - Pro: It is safe to proceed with thoracoabdominal aortic aneurysm surgery after
      encountering a bloody tap during cerebrospinal fluid catheter placement.

PMID- 16616676
TI  - Con: Surgery should not proceed when a bloody tap occurs during spinal drain
      placement for elective thoracoabdominal aortic surgery.

PMID- 16616677
TI  - Aneurysm of the left sinus of Valsalva?

PMID- 16616678
TI  - Sinus of Valsalva aneurysm?

PMID- 16616679
TI  - A duplicate inferior vena cava?

PMID- 16616680
TI  - Pseudoaneurysm after attempted left internal jugular venous cannulation: when is
      ultrasound-assistance indicated?

PMID- 16616681
TI  - Difficult intubation in pediatric cardiac surgery.

PMID- 16616682
TI  - Combination of low-dose phenoxybenzamine and sodium nitroprusside in children
      undergoing cardiac surgery.

PMID- 16616684
TI  - Bispectral index in total circulatory arrest: what is the safe value?

PMID- 16616685
TI  - Antioxidative stress proteins and their gene expression in brown trout (Salmo
      trutta) from three rivers with different heavy metal levels.
AB  - Three populations of brown trout (Salmo trutta) exposed to different metal levels
      in their natural environments, were studied with respect to antioxidants
      metallothionein (MT), superoxide dismutase (SOD) and catalase (CAT) as well as
      for corresponding mRNA levels. In addition, mRNA levels were studied for
      glutathione peroxidase (GPx) and glutathione reductase (GR). The Cd/Zn-exposed
      trout (Naustebekken River) had higher accumulated levels of Cd, Cu and Zn in
      gills, and higher levels of MT (both protein and mRNA) in liver and kidney as
      well as in gills compared to the Cu-exposed trout (Rugla River) and trout from an
      uncontaminated reference river (Stribekken River). Less MT found in the Cu
      exposed trout may increase susceptibility to oxidative stress, but no higher
      levels of antioxidant mRNAs were found in gills of these trouts. The data
      indicated that chronic exposures of brown trout to Cd, Zn and/or Cu did not
      involve maintenance of high activities of SOD and CAT enzymes in gills, although
      SOD mRNA levels were higher in the Cd/Zn-exposed trout. In livers, mRNA levels of
      SOD, CAT and GPx were higher in the metal-exposed trout, but in the case of GR
      this was only seen in kidneys of Cd/Zn-exposed trout. However, both metal-exposed
      groups had higher activities of SOD enzyme in liver compared to the unexposed
      reference trout, and CAT activity was found to be higher in kidneys of Cu-exposed
      trout. The Cu-exposed trout did not seem to rely on MT production to avoid Cu
      toxicity in gills, but rather by keeping the Cu uptake at a low level. A
      coordinated expression of different stress genes may also be important in chronic
      metal exposure. It may be concluded that the observed metal effects relies on
      acclimation rather than on genetic adaptation in the metal exposed populations.

PMID- 16616687
TI  - Miguel Ruiz's four agreements as applied to difficult conversations.

PMID- 16616688
TI  - Resources and case law.

PMID- 16616689
TI  - Young nurse causes embarrassment.

PMID- 16616690
TI  - Multistate nurse licensure in case management.
AB  - To encourage case managers and CM employers to support compliance with multistate
      nursing licensure, the Case Management Society of America (CMSA) board of
      directors has revised an earlier position statement on multistate nursing
      licensure in case management. According to CMSA President Susan Rogers, RN, BSN,
      CCM, "CMSA's fundamental position on this topic remains unchanged. What's
      different is a more assertive position in support of appropriate safeguards for
      our members and case managers nationwide."

PMID- 16616691
TI  - What nurse case managers need to know about the Nurse Licensure Compact.
AB  - In the late 1990s, the National Council of State Boards of Nursing (NCSBN) began
      exploring several nurse-licensing models that would simplify government processes
      and remove regulatory barriers, while increasing access to safe nursing care. The
      NCSBN decided on the mutual-recognition model (similar to that used for state
      driver's licenses), which allows a nurse to practice in states other than the one
      in which the license was issued, usually the state of residency, as long as that
      individual acknowledges that he or she is subject to each state's practice laws
      and discipline. Like the driver's license model, nursing practice across state
      lines is allowed, whether physical or electronic, unless the nurse is under
      discipline or a monitoring agreement that restricts practice across state lines.

PMID- 16616692
TI  - The jury shall decide!
AB  - Those familiar with the code of professional conduct, set forth by the Commission
      for Case Manager Certification (CCMC), know of the expectations for case
      managers' behaviors. Professionals making application for certification must sign
      a statement committing to case management practice consistent with the law and
      the ethical requirements for their primary profession. The case manager's role
      and function have been repeatedly studied, based on input from the field and
      review of the literature. The outcomes are consistent with these foundations:
      advocate for the patient/client and act in the patient's best interest.
      Increasingly, case managers are becoming the focus of a lawsuit when it appears
      that they have done other than advocate for the individual or act in the
      individual's best interest. The three cases and information presented here are
      all public information; however, they have been disguised for publication
      purposes. Should one or all of these cases proceed to court, the jury shall
      decide if the case manager's actions were consistent with the standard of care.
      Reflect on your own practice as you consider each actual case.

PMID- 16616693
TI  - Putting case management to the ultimate test: rebuilding New Orleans after
      Katrina, Part 1.

PMID- 16616694
TI  - Meeting the medical necessity requirement.
AB  - Establishing the medical necessity of a procedure is increasingly important--and
      complex--because medical techniques are evolving faster each year. Add the rising
      number, cost, and complexity of innovative and experimental medical treatments to
      the easy accessibility of medical information now available to consumers and you
      have all the criteria for confusing medical fact with medical potential. It's
      difficult for specialists and subspecialist physicians to keep up with their
      field--and impossible for case managers.

PMID- 16616695
TI  - Helping patients become more educated about provider quality.
AB  - Many people won't buy a computer without first reading the product reviews on or
      decide on a new car until they've consulted Consumer Reports. For most big-ticket
      purchases, comparison shopping is routine. But when it comes to making health
      care decisions, consumers often don't know where to turn to find objective
      information about physicians and hospitals.

PMID- 16616696
TI  - A generic minimization random allocation and blinding system on web.
AB  - BACKGROUND: Minimization is a dynamic randomization method for clinical trials.
      Although recommended by many researchers, the utilization of minimization has
      been seldom reported in randomized trials mainly because of the controversy
      surrounding the validity of conventional analyses and its complexity in
      implementation. However, both the statistical and clinical validity of
      minimization were demonstrated in recent studies. Minimization random allocation
      system integrated with blinding function that could facilitate the implementation
      of this method in general clinical trials has not been reported. SYSTEM OVERVIEW:
      The system is a web-based random allocation system using Pocock and Simon
      minimization method. It also supports multiple treatment arms within a trial,
      multiple simultaneous trials, and blinding without further programming. METHODS:
      This system was constructed with generic database schema design method, Pocock
      and Simon minimization method and blinding method. It was coded with Microsoft
      Visual Basic and Active Server Pages (ASP) programming languages. And all dataset
      were managed with a Microsoft SQL Server database. Some critical programming
      codes were also provided. SIMULATIONS AND RESULTS: Two clinical trials were
      simulated simultaneously to test the system's applicability. Not only balanced
      groups but also blinded allocation results were achieved in both trials.
      DISCUSSIONS AND CONCLUSIONS: Practical considerations for minimization method,
      the benefits, general applicability and drawbacks of the technique implemented in
      this system are discussed. Promising features of the proposed system are also
      summarized.

PMID- 16616697
TI  - Bridging the gap between biological and clinical informatics in a graduate
      training program.
AB  - Several training programs in biomedical informatics in the United States are
      attempting to integrate biological and clinical informatics. However, significant
      differences in the cultures underlying these two disciplines pose barriers to a
      uniform educational solution. This paper recounts the experience at Columbia
      University in adapting a graduate program with an initial focus on clinical
      informatics to train bioinformaticians. The analysis begins by considering the
      development of the medical and biological informatics cultures over a 17-year
      period. Then we review how two separate curricula evolved to serve the needs of
      each group. Interviews with bioinformatics students and faculty indicated some
      dissatisfaction with the curriculum that developed within clinical informatics.
      Their comments are considered in the light of an analysis of the relationship
      between the application domains of biomedical informatics as a discipline. In
      response, a new curriculum was developed in which bioinformatics and clinical
      informatics are regarded as subdivisions of the same subject. A key feature of
      this curriculum is a new course, Theory and Methods in Biomedical Informatics,
      which presents informatics principles in their general form, and illustrates
      their application with examples drawn from across the biomedical spectrum. The
      paper concludes with suggestions for integrating informatics training programs at
      other institutions.

PMID- 16616698
TI  - The genome-enabled electronic medical record.
AB  - The integration of patient-specific genomic information into the electronic
      medical record (EMR) will create many opportunities to improve patient care. Key
      to the successful incorporation of genomic information into the EMR will be the
      development of laboratory information systems capable of appropriately formatting
      molecular diagnostic and cytogenetic findings in the EMR. Due to the lack of
      granular genomics-related content in existing medical vocabularies, the adoption
      of new standards for describing clinically significant genomic information will
      be an important step toward recognizing the genome-enabled EMR. Appropriate
      capture of patient-specific genomic results in the EMR will generate new
      opportunities to utilize this information in clinical decision support, including
      automated response to pharmacogenomic-based risks.

PMID- 16616699
TI  - Eicosapentaenoic acid and docosahexaenoic acid modulate mitogen-activated protein
      kinase activity in endothelium.
AB  - Omega-3 polyunsaturated fatty acids (PUFA) regulate inflammation and
      immunoreaction partially via affecting endothelial functions. However, the
      intracellular signaling mechanisms for inhibiting endothelial activation by omega
      3 PUFA remain unclear. We investigated the effects of eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA) on mitogen-activated protein kinases (MAPK) of
      endothelium. We analyzed the expression of extracellular signal-related kinases
      (ERK1/2), Jun amino-terminal kinases (JNK), and p38 mRNA by real-time RT-PCR and
      the kinases activity by western blotting in tumor necrosis factor-alpha (TNF
      alpha)-activated human umbilical vein endothelial cells (HUVEC). We observed that
      EPA or DHA alone significantly reduced the TNF-alpha-induced activation of p38
      and JNK kinases at a concentration of 20 microM, but EPA is a more potent
      inhibitor than DHA. In contrast, both EPA and DHA significantly counteracted the
      TNF-alpha-mediated deactivation of ERK1/2 kinases. Meanwhile, both EPA and DHA
      significantly attenuated the TNF-alpha-induced expression of p38 and ERK1/2 mRNA,
      and DHA but not EPA also reduced the TNF-alpha-induced JNK mRNA expression. We
      present data show that both EPA and DHA alone diminish activation of p38 and JNK
      kinases, while maintaining the activation of ERK1/2 kinases of TNF-alpha
      stimulated HUVEC. This may contribute to the inhibiting effects of omega-3 PUFA
      on endothelial activation by proinflammatory stimuli.

PMID- 16616700
TI  - Tachykinins and tachykinin receptors in the gut, with special reference to NK2
      receptors in human.
AB  - Tachykinins (TKs), substance P (SP), neurokinin A (NKA) and B (NKB) are important
      peptide modulators of intestinal motility in animal species studied so far,
      including humans. Modulation of motility by TKs can occur at various levels,
      since these peptides are expressed in cholinergic excitatory motor neurons
      projecting to both circular and longitudinal muscle, interneurons, and intramural
      and extramural sensory neurons. The effects of SP, NKA and NKB are preferentially
      mediated through the stimulation of NK1, NK2 and NK3 receptors, respectively;
      however, the selectivity of natural TKs for their preferred receptors is
      relative. In addition, SP and NKA are expressed in similar quantities in the
      human intestine and adequate stimuli can release similar amount of these TKs from
      enteric nerves. Furthermore, a single anatomical substrate can express more than
      one TK receptor type, so that the blockade of a single receptor type may not
      reveal functional effects in integrated models of motility. In isolated human
      small intestine and colon circular muscle strips, both NK1 and NK2 receptors
      mediate contractile effects. Indeed, in the human small intestine, smooth muscle
      electrical and motor events induced by electrical field stimulation (EFS) can
      involve either or both NK1 and NK2 receptors or these latter receptors
      predominantly, depending on the experimental conditions. In contrast, in the
      human colonic smooth muscle, only the NK2 receptor-mediated component of the
      response to EFS is prominent and some evidence would suggest that this component
      is the main excitatory motor mechanism at this level. Furthermore, a NK2 receptor
      mediated secretory component in the human colonic mucosa has been recently
      demonstrated. Thus, it could be speculated that the blockade of both NK1 and NK2
      receptors will be necessary to antagonise motor effects induced by exogenous
      administration or endogenous release of TKs in the small intestine, whereas the
      blockade of the NK2 receptors would be sufficient to disrupt physiological motor
      and, possibly, secretory activity at the colonic level. Available evidence
      indicates that, in healthy volunteers, the infusion of NKA (25 pmol/kg/min i.v.)
      stimulated small intestine motility and precipitated a series of intestinal and
      non-intestinal adverse events. Nepadutant (8 mg i.v.), a selective NK2 receptor
      antagonist, antagonised small intestine motility induced by NKA and prevented
      associated intestinal adverse events. In another study, the same dose of
      nepadutant increased colo-rectal compliance during isobaric balloon distension in
      healthy volunteers pretreated with a glycerol enema, disclosing a NK2 receptor
      mediated component in the regulation of colonic smooth muscle tone. However, the
      prolonged blockade of NK2 receptors by nepadutant (16 mg i.v. b.i.d. for 8 days)
      did not affect bowel habits, neither in term of movements nor of stool
      consistency. Altogether, these results indicate that, even when there is a
      significant redundance in the effects of TKs and in the role of their receptors,
      the selective blockade of tachykinin NK2 receptors can have functional
      consequences on human intestinal motility and perception, but this can occur
      without the disruption of the physiological functions.

PMID- 16616701
TI  - Region-specific distribution of the P2Y4 receptor in enteric glial cells and
      interstitial cells of Cajal within the guinea-pig gastrointestinal tract.
AB  - Although there is pharmacological evidence to assume that the P2Y4 receptor is a
      regulator of epithelial ion transport, no detailed data about its distribution
      within the gut are available. Therefore, this study, using whole mounts and
      cryosections, aimed to reveal the expression pattern of P2Y4 along the entire
      guinea-pig gastrointestinal tract. P2Y4 immunoreactivity was absent from enteric
      neurons but present in enteric glial cells of the stomach, small and large
      intestine. In the esophagus, P2Y4 appeared to be exclusively located within
      striated muscle cells. P2Y4 showed also a region dependency regarding its
      presence in different subpopulations of interstitial cells of Cajal: in myenteric
      interstitial cells of Cajal in the stomach and ileum; in some intramuscular
      interstitial cells in the stomach and cecum; in some deep muscular plexus
      interstitial cells in the ileum; and in some submucosal surface interstitial
      cells in the colon. These results and the knowledge that P2Y4 activation causes
      intracellular Ca2+ recruitment led us to suggest that P2Y4 in enteric glia plays
      a modulatory role in intercellular Ca2+ waves, while P2Y4 in interstitial cells
      of Cajal modulates intracellular Ca2+ oscillations.

PMID- 16616702
TI  - Optical recording of vagal pathway formation in the embryonic brainstem.
AB  - Multiple-site optical recording with a fast voltage-sensitive dye, absorption dye
      NK2761, was used to study the developmental organization of functional synaptic
      networks in the vagal pathway. Glutamatergic excitatory postsynaptic potentials
      (EPSPs) evoked by vagus nerve stimulation was first detected from the nucleus of
      the tractus solitarius (NTS) at embryonic day 7 (E7) in chick embryos and E15 in
      rat embryos, when morphological differentiation of pre- and postsynaptic neurons
      is incomplete. When extracellular Mg2+ was removed, small EPSPs were elicited at
      E6 in chick embryos and E14 in rat embryos. These results suggest that synaptic
      function mediated by N-methyl-D-aspartate (NMDA) receptors is latently generated
      1 day before the expression of glutamatergic EPSP. Functional synapses related to
      the glossophyaryngeal nerve appear to be generated at the same time as the vagus
      nerve, but their spatial distribution was different from that of the vagus nerve.
      We further investigated the development of second synaptic pathways from the NTS
      to higher centers, and found that neuronal circuits from the NTS are already
      generated when the primary afferents form functional synapses with NTS neurons.

PMID- 16616703
TI  - Localized gene transfer and its application for the study of central
      cardiovascular control.
AB  - The arterial baroreceptor reflex is the major feedback control system that acts
      to stabilize blood pressure. Abnormalities of this reflex are considered to be an
      underlying mechanism in the cardiovascular diseases such as hypertension and
      heart failure. There is accumulating evidence, however, that central nervous
      system mechanisms are involved in the enhanced sympathetic drive that occurs in
      these disease states. This article reviews studies performed in our laboratory in
      which a gene transfer technique, in combination with other methods, was used to
      determine the functional role of the central control of cardiovascular
      regulation. We developed a technique to transfer adenovirus vectors encoding
      specific genes into the nucleus tractus solitarii (NTS) or the rostral ventral
      medulla (RVLM) of rats in vivo. We applied this technique to hypertensive rats as
      well as in mice with heart failure to explore the pathophysiological significance
      of nitric oxide, reactive oxygen species, and Rho-kinase.

PMID- 16616704
TI  - Effects of gastrointestinal inflammation on enteroendocrine cells and enteric
      neural reflex circuits.
AB  - Inflammation of the gastrointestinal (GI) tract has pronounced effects on GI
      function. Many of the functions of the GI tract are subject to neural regulation
      by the enteric nervous system (ENS) and its extrinsic connections. Therefore, it
      is possible that inflammatory effects on the ENS contribute to altered function
      during GI inflammation. The reflex circuitry of the ENS is comprised of sensory
      transducers in the mucosa (enteroendocrine cells), afferent neurons, interneurons
      and motor neurons. This review focuses on recent data that describe inflammation
      induced changes to the ENS and mucosal enteroendocrine cells. Studies of tissues
      from patients with inflammatory bowel disease (IBD) and from animal models of IBD
      have demonstrated marked changes in mucosal enteroendocrine cell signaling. These
      changes, which have been studied most intensely in 5-HT-containing
      enterochromaffin cells, involve changes in the number of cells, their signaling
      molecule content or their means of signal termination. Morphological evidence of
      enteric neuropathy during inflammation has been obtained from human samples and
      animal models of IBD. The neuropathy can reduce the number of enteric neurons in
      the inflamed region and is often accompanied by a change in the neurochemical
      coding of enteric neurons, both in the inflamed region and at distant sites.
      Electrophysiological recordings have been made from enteric neurons in inflamed
      regions of the colon of animal models of IBD. These studies have consistently
      found that inflammation increases excitability of intrinsic primary afferent
      neurons and alters synaptic transmission to interneurons and motor neurons. These
      data set the stage for a comprehensive examination of the role of altered
      neuronal and enteroendocrine cell signaling in symptom generation during GI
      inflammation.

PMID- 16616709
TI  - Expression pattern of Filamin-240 in Drosophila blood cells.
AB  - The expression pattern of Filamin-240 was studied in subsets of Drosophila blood
      cells by means of immunofluorescent staining and Western blot analysis with use
      of an antibody specific to a "filamin-folding domain", a consensus motif profile
      generated from the 20 existing filamin repeats. Expression of Filamin-240 is
      restricted to lamellocytes - a special blood cell type of the cellular immune
      response - and is involved in the regulation of lamellocyte development. In the
      cher1 homozygous larvae, which lack Filamin-240 protein, a vigorous lamellocyte
      differentiation occurs which is further enhanced upon in vivo immune challenge by
      a parasitic wasp, Leptopilina boulardi. By introducing a full-length transgene
      encoding the Drosophila Filamin-240 protein into the cher1 Filamin-deficient
      homozygous mutant, the mutant blood cell phenotype was rescued. These data
      demonstrate that the expression of Filamin-240 is strictly lamellocyte specific
      in Drosophila blood cells and that the protein is a suppressor of lamellocyte
      development.

PMID- 16616705
TI  - Airway-related vagal preganglionic neurons express multiple nicotinic
      acetylcholine receptor subunits.
AB  - Nicotine acting centrally increases bronchomotor tone and airway secretion,
      suggesting that airway-related vagal preganglionic neurons (AVPNs) within the
      rostral nucleus ambiguus (rNA) express nicotinic acetylcholine receptors
      (nAChRs). In the present study, we examined the three main functionally
      characterized subtypes of nAChRs in the CNS, the alpha7 homomeric and alpha4beta2
      heteromeric receptors. First, we characterized the expression of these subunits
      at the message (mRNA) and protein levels in brain tissues taken from the rNA
      region, the site where AVPNs are located. In addition, double labeling
      fluorescent immunohistochemistry and confocal laser microscopy were used to
      define the presence of alpha7, alpha4, and beta2 nAChRs on AVPNs that were
      retrogradely labeled with cholera toxin beta subunit (CTb), injected into the
      upper lung lobe (n=4) or extrathoracic trachea (n=4). Our results revealed
      expression of all three studied subunits at mRNA and protein levels within the
      rNA region. Furthermore, virtually all identified AVPNs innervating
      intrapulmonary airways express alpha7 and alpha4 nAChR subunits. Similarly, a
      majority of labeled AVPNs projecting to extrathoracic trachea contain alpha7 and
      beta2 subunits, but less than half of them show detectable alpha4 nAChR traits.
      These results suggest that AVPNs express three major nAChR subunits (alpha7,
      alpha4, and beta2) that could assemble into functional homologous or heterologous
      pentameric receptors, mediating fast and sustained nicotinic effects on
      cholinergic outflow to the airways.

PMID- 16616710
TI  - Early postnatal exposure to allergen and ozone leads to hyperinnervation of the
      pulmonary epithelium.
AB  - Airway injury in infant monkeys exposed to ozone and/or house dust mite allergen
      (HDMA) is associated with a loss of epithelial innervation. In this study, we
      evaluated for persistence/recovery of the altered epithelial innervation. Thirty
      day-old rhesus monkeys were exposed to repeated episodes of HDMA and/or ozone
      from 1 to 6 months of age and subsequently allowed to recover for 6 months in the
      absence of further ozone exposure and/or minimal HDMA challenge (sufficient to
      maintain allergen sensitization). At 1 year of age, nerve density in
      intrapulmonary airways was immunohistochemically evaluated using antibodies
      directed against protein gene product 9.5. Hyperinnervation and irregular
      epithelial nerve distribution was observed in both HDMA- and ozone-exposed
      groups; most prominent alterations were observed in animals exposed to HDMA plus
      ozone. Therefore, while adaptive mechanisms exist that re-establish epithelial
      innervation following cessation or diminution of exposure to HDMA and/or ozone,
      the recovery is associated with persistent proliferative mechanisms that result
      in hyperinnervation of the airways.

PMID- 16616711
TI  - The acute abdomen in the newborn.
AB  - The acute abdomen in the newborn provides challenging problems from many aspects,
      not only with regard to diagnosis, resuscitation and treatment, but also now with
      prenatal management. Most conditions are uncommon and treatment in specialist
      centres enables concentration of appropriate resources and expertise. Co
      morbidity is common, particularly in the preterm or low birth weight infant. A
      multi-disciplinary team of surgeons, anaesthetists, neonatologists, radiologists,
      cardiologists, obstetricians, nurses, physiotherapists and other health
      professionals experienced in dealing with extremely small infants will provide
      the best outcome. The infant should be resuscitated and, as soon as conditions
      permit, transferred to a specialist surgical centre with intravenous fluids,
      gastric tube drainage and circulatory, respiratory and general support as needed.
      This involves close liaison within healthcare networks and readily available
      patient transfer facilities. Surgery itself should be carried out in a theatre
      fully equipped for neonatal surgery. A gentle touch is essential because of the
      fragility of the tissues, and painstaking care should be taken with blood loss.

PMID- 16616712
TI  - Hydrogen peroxide-induced oxidative stress in MC3T3-E1 cells: The effects of
      glutamate and protection by purines.
AB  - Glutamate has toxic effects on a number of tissues, partly by inducing toxic
      (e.g., oxidative) stress, whereas adenosine can be protective. Since there is
      evidence that glutamate and adenosine receptors are present in bone, we set out
      to study whether oxidative stress, induced by hydrogen peroxide (H2O2), affected
      viability in the MC3T3-E1 osteoblast-like cell line and whether treatment with
      adenosine receptor ligands attenuated this. Hydrogen peroxide (100 microM to 5
      mM) reduced the viability of the MC3T3-E1 cells, while catalase reversed this
      cell loss and itself had some mitogenic effect. Superoxide dismutase (SOD)
      increased the number of viable cells alone but failed to modify significantly the
      effect of H2O2 treatments. Glutamate (100 microM, 1 mM) and NMDA (10 microM),
      applied alone for up to 1 h, had a mitogenic effect (P < 0.05). Adenosine A1 and
      A2A receptor agonists and antagonists at low and high concentrations showed some
      mitogenic effects when added singly, but only high concentrations of the agonists
      showed significant protection against cell death resulting from H2O2 treatments.
      Contributions from both apoptotic and necrotic pathways were implicated in the
      H2O2-induced cell loss as was demonstrated by the use of the caspase-3 inhibitor
      (Z-DEVD-fmk) and the PARP-1 inhibitor (DPQ). The results demonstrate that
      hydrogen peroxide was toxic to MC3T3-E1 cells, whereas glutamate was not and may
      even have a trophic influence. Adenosine and its receptors afforded some
      protection to osteoblasts against cellular death mediated partly by apoptosis and
      partly by necrosis.

PMID- 16616713
TI  - Low oxygen tension inhibits osteogenic differentiation and enhances stemness of
      human MIAMI cells.
AB  - We recently reported the isolation of a unique subpopulation of human stromal
      cells from bone marrow (BM) termed marrow-isolated adult multilineage inducible
      (MIAMI) cells, capable of differentiating in vitro into mature-like cells from
      all three germ layers. The oxygen tension (pO2) in BM ranges from 1 to 7%, which
      prompted us to examine the role of pO2 in regulating the capacity of MIAMI cells
      both to self-renew and maintain their pluripotentiality (stemness) or to progress
      toward osteoblastic differentiation. MIAMI cells were grown under low-pO2
      conditions (1, 3, 5, and 10% oxygen) or air (21% oxygen). The proliferation rate
      of cells exposed to 3% oxygen (3 days) increased, resulting in cell numbers more
      than threefold higher than those of cells exposed to air (at 7 days). In cells
      grown under osteoblastic differentiation conditions, the expression of the
      osteoblastic markers osteocalcin, bone sialoprotein, osterix, and Runx2 and
      alkaline phosphatase activity was upregulated when incubated in air; however, it
      was blocked at low (3%) pO2. Similarly, biomineralization of long-term cell
      cultures was high under osteoblastic differentiation conditions in air but was
      undetectable at low (3%) pO2. In contrast, low pO2 upregulated mRNAs for OCT-4,
      REX-1, telomerase reverse transcriptase, and hypoxia-inducible factor-1 alpha,
      and increased the expression of SSEA-4 compared to air. Moreover, the expression
      of embryonic stem cell markers was sustained even under osteogenic culture
      conditions. Similar results were obtained using commercially available marrow
      stromal cells. We hypothesize a physiological scenario in which primitive MIAMI
      cells self-renew while localized to areas of low pO2 in the bone marrow, but tend
      to differentiate toward osteoblasts when they are located closer to blood vessels
      and exposed to higher pO2. Our results strongly suggest that maintaining
      developmentally primitive human cells in vitro at low pO2 would be more
      physiological and favor stemness over differentiation.

PMID- 16616714
TI  - Synthesis and thermal characterization of new ternary chelates of piroxicam and
      tenoxicam with glycine and DL-phenylalanine and some transition metals.
AB  - The ternary chelates of piroxicam (Pir) and tenoxicam (Ten) with Fe(II), Fe(III),
      Co(II), Ni(II), Cu(II) and Zn(II) in the presence of various amino acids such as
      glycine (Gly) or dl-phenylalanine (PhA) were prepared and characterized with
      different physicochemical methods. IR spectra confirm that Pir and Ten behave as
      a neutral bidentate ligand coordinated to the metal ions via the pyridine-N and
      carbonyl group of the amide moiety. Gly molecule acted as a uninegatively
      monodentate ligand and coordinate to the metal ions through its deprotonated
      carboxylic group. In addition, PhA acted as a uninegatively bidentate ligand and
      coordinate to the metal ions through its deprotonated carboxylic and amino
      groups. The solid reflectance spectra and magnetic moment measurements confirm
      that all the chelates have octahedral geometrical structures while Cu(II)- and
      Zn(II)-ternary chelates with PhA have square planar geometrical structures.
      Thermal behaviour of the complexes is extensively studied using TG and DTA
      techniques. TG results show that water molecules (hydrated and coordinated) and
      anions are removed in the first and second steps while Gly, PhA, Pir and Ten are
      decomposed in the next and subsequent steps. The pyrolyses of the chelates into
      different gases are observed in the DTA curves as exo- or endothermic peaks.
      Also, phase transition states are observed in some chelates. Different
      thermodynamic parameters are calculated using Coats-Redfern method and the
      results are interpreted.

PMID- 16616715
TI  - Thrombotic thrombocytopenic purpura secondary to Streptococcus.
AB  - We describe a 16 year old female who developed thrombotic thrombocytopenic
      purpura (TTP) following infection due to Streptococcus. Initially presenting a
      fever and systemic upset she progressed to develop dialysis dependent acute renal
      failure, seizures, thrombocytopenia and a haemolytic anaemia--the pentad of
      features seen in TTP. Prior to the diagnosis she was found to have unexplained
      and previously undescribed MRI findings of diffuse increased signal intensity in
      the white matter of the left cerebellar hemisphere posteriorly and also increased
      signal intensity in the overlying cortex. She was commenced on plasmapheresis,
      and her anaemia, thrombocytopenia, creatinine and LDH all fully responded. In
      addition, she had no further seizures following plasmapheresis and has not
      relapsed to date. We review both the rare association of TTP and streptococcal
      infection, and the neuroradiological findings described in the literature. This
      is only the third case report describing TTP following streptococcal infection,
      and only the second in the era of plasmapheresis.

PMID- 16616716
TI  - Consequences of exercise-induced respiratory muscle work.
AB  - We briefly review the evidence for a hypothesis, which links the ventilatory
      response to heavy intensity, sustained exercise-to-exercise performance
      limitation in health. A key step in this linkage is a respiratory muscle fatigue
      induced metaboreflex, which increases sympathetic vasoconstrictor outflow,
      causing reduced blood flow to locomotor muscles and locomotor muscle fatigue. In
      turn, the limb fatigue comprises an important dual contribution to both
      peripheral and central fatigue mechanisms, which contribute to limiting exercise
      performance. Clinical implications for respiratory limitations to exercise in
      patients with chronic obstructive lung disease (COPD) and chronic heart failure
      (CHF) are discussed and key unresolved problems are outlined.

PMID- 16616717
TI  - The assessment of the gingival capillary density with orthogonal spectral
      polarization (OPS) imaging.
AB  - OBJECTIVE: In this study we evaluated the inter-observer agreement in the
      assessment of gingival capillary density using Orthogonal Polarization Spectral
      Imaging. METHODS: In this study gingival capillary density of 100 healthy
      subjects was determined by 2 independent observers. Agreement was quantified by
      calculation of the mean differences between the observers and the standard
      deviation of this difference and the limits of agreement. Reliability was
      quantified by means of the intraclass correlation coefficient (ICC). RESULTS:
      Fifty males and 50 females were included in the study. The mean age for males was
      20+/-1.2 years and for females 20+/-1.4. OPS images showed remarkable good
      quality images of the gingival microcirculation. The interclass correlation
      between the 2 observers was 0.63 while the interclass correlation for the 6
      measurements in observer 1 was 0.95 and 0.94 for observer 2. The mean capillary
      density for females in observer 1 was 83.69+/-16.4 and 83+/-16.0 in observer 2,
      versus 60.55+/-12.3 for observer 1 and 60.4+/-12.1 for males. The mean
      quantitative functional capillary density in male students was 60.48+/-10.7,
      compared to 83.45+/-13.5 in female students. CONCLUSIONS: OPS imaging enabled for
      the first time direct in vivo visualization and quantification of human
      functional gingival capillary density in healthy medical students. The inter
      observer agreement was found to be good to fair on the quantification of gingival
      capillary density between the two independent observers. The intracorrelation
      coefficient (0.95) was excellent when assessing the reliability of one observer.

PMID- 16616718
TI  - The transcription factor Cdx2 regulates the intestine-specific expression of
      human peptide transporter 1 through functional interaction with Sp1.
AB  - H(+)/peptide cotransporter 1 (PEPT1, SLC15A1) localized at the brush-border
      membranes of intestinal epithelial cells plays important roles in the intestinal
      absorption of small peptides and a variety of peptidemimetic drugs. We previously
      demonstrated that transcription factor Sp1 functions as a basal transcriptional
      regulator of human PEPT1. However, the factor responsible for the intestine
      specific expression of PEPT1 remains unknown. In the present study, we
      investigated the effect of the intestinal transcription factors on the
      transcription of the PEPT1 gene and found that only Cdx2 markedly trans-activated
      the PEPT1 promoter. However, the promoter region responsible for this effect
      lacked a typical Cdx2-binding sequence, but instead, possessed some Sp1-binding
      sites. In vitro experiments using Caco-2 cells showed that (1) mutation of the
      Sp1-binding site diminished the effect of Cdx2, (2) co-expression of Cdx2 and Sp1
      synergistically trans-activated the PEPT1 promoter and (3) Sp1 protein was
      immunoprecipitated with Cdx2 protein. These results raise the possibility that
      Cdx2 modulates the PEPT1 promoter by interaction with Sp1. The significance of
      Cdx2 in vivo for PEPT1 regulation was shown by the determination of mRNA levels
      of Cdx2 and PEPT1 in human tissue. In gastric samples, some with intestinal
      metaplasia, the levels of PEPT1 and Cdx2 mRNA were highly correlated. Taken
      together, the present study suggests that Cdx2 plays a key role in the
      transcriptional regulation of the intestine-specific expression of PEPT1,
      possibly through interaction with Sp1.

PMID- 16616719
TI  - Lack of evidence for association of the serotonin transporter gene SLC6A4 with
      autism.
AB  - BACKGROUND: The serotonin transporter (5-HTT) has long been considered likely to
      play a role in autism. Hyperserotonemia has been consistently found in a
      proportion of autistic patients, and the use of selective serotonin reuptake
      inhibitors (SSRIs) can have a positive effect in treating some symptoms of
      autism. Specific variants of the 5-HTT gene, SLC6A4, especially the insertion
      deletion 5-HTTLPR promoter locus, have been found to modulate its expression and
      transporter function. METHODS: We examined the transmission of the short or long
      allele of 5-HTTLPR locus to affected individuals, using a large cohort of 352
      families. In addition, we screened five single nucleotide polymorphisms (SNPs) in
      the 5' region of SLC6A4 previously reported to be positively associated with
      autism, as well as 4 additional SNPs also in the 5' region. RESULTS: No
      association of the 5-HTTLPR locus with autism was found. Furthermore, no evidence
      for association of any of the nine SNPs covering the SLC6A4 gene, or any of their
      haplotypes, was observed in our study. Using obsessive-compulsive behaviors
      (OCB), severe OCBs or rigid-compulsive subsets of our cohort gave the same
      negative results. CONCLUSIONS: SLC6A4 variants do not appear to be significantly
      involved in the liability to autism.

PMID- 16616720
TI  - Mechanisms of action of medicines for schizophrenia and bipolar illness: status
      and limitations.
AB  - This paper is not a comprehensive review of the literature. Rather, it is a
      viewpoint based upon advances in other fields of medicine and genetics that may
      provide a model for guiding research in psychiatry. The paper discusses the major
      limitations of the medicines currently used to treat schizophrenia and bipolar
      illness. The limitations in our understanding of the molecular causes of these
      two illnesses and our lack of a clear mechanism of action for many of the
      medicines used to treat them continue to confound the field and impede progress
      towards finding novel treatments. Until the genetic bases of bipolar illness and
      schizophrenia are unambiguously identified, progress towards improved diagnosis
      and treatment will be retarded. An approach to identifying risk genes based upon
      association studies starting with very large sample sizes based upon currently
      available diagnoses of bipolar disorder and schizophrenia is advocated.

PMID- 16616721
TI  - Language processing and human voice perception in schizophrenia: a functional
      magnetic resonance imaging study.
AB  - BACKGROUND: Neuroimaging studies have demonstrated either reduced left
      lateralized activation or reversed language dominance in schizophrenia. These
      findings of left hemispheric dysfunction could be attributed to language
      processing tasks, which activate mainly left hemispheric function. Recent
      functional magnetic resonance imaging studies reported right-lateralized temporal
      activation by human voice perception, but few studies have investigated
      activation by human voice in schizophrenia. We aimed to clarify the cerebral
      function of language processing in schizophrenia patients by considering cerebral
      activation of human voice perception. METHODS: Fourteen right-handed
      schizophrenia patients and 14 right-handed controls with matched handedness, sex,
      and education level were scanned by functional magnetic resonance imaging while
      listening to sentences (SEN), reverse sentences (rSEN), and identifiable non
      vocal sounds (SND). RESULTS: Under the SEN-SND and SEN-rSEN contrasts including
      language processing, patients showed less activation of the left hemisphere than
      controls in the language-related fronto-tempo-parietal region, hippocampus,
      thalamus and cingulate gyrus. Under the rSEN-SND contrast including human voice
      perception, patients showed less activation than controls in the right
      lateralized temporal cortices and bilateral posterior cingulate. CONCLUSIONS: Our
      results indicate that schizophrenia patients have impairment of broader bilateral
      cortical-subcortical regions related to both the semantic network in the left
      hemisphere and the voice-specific network in the right hemisphere.

PMID- 16616722
TI  - Early life stress and morphometry of the adult anterior cingulate cortex and
      caudate nuclei.
AB  - BACKGROUND: Early life stress (ELS) is linked to adult psychopathology and may
      contribute to long-term brain alterations, as suggested by studies of women who
      suffered childhood sexual abuse. We examine whether reported adverse ELS defined
      as stressful and/or traumatic adverse childhood events (ACEs) is associated with
      smaller limbic and basal ganglia volumes. METHOD: 265 healthy Australian men and
      women without psychopathology or brain disorders were studied. ACEs were assessed
      by the ELSQ and current emotional state by the DASS. Anterior cingulate cortex
      (ACC), hippocampus, amygdala, and caudate nucleus volumes were measured from T1
      weighted MRI. Analyses examined ROI volumetric associations with reported ACEs
      and DASS scores. RESULTS: Participants with greater than two ACEs had smaller ACC
      and caudate nuclei than those without ACEs. A significant association between
      total ACEs and ROI volumes for these structures was observed. Regression analysis
      also revealed that ELS was more strongly associated than current emotional state
      (DASS) with these ROI volumes. CONCLUSIONS: Reported ELS is associated with
      smaller ACC and caudate volumes, but not the hippocampal or amygdala volumes. The
      reasons for these brain effects are not entirely clear, but may reflect the
      influence of early stress and traumatic events on the developing brain.

PMID- 16616723
TI  - Reduced auditory processing capacity during vocalization in children with
      Selective Mutism.
AB  - BACKGROUND: Because abnormal Auditory Efferent Activity (AEA) is associated with
      auditory distortions during vocalization, we tested whether auditory processing
      is impaired during vocalization in children with Selective Mutism (SM). METHODS:
      Participants were children with SM and abnormal AEA, children with SM and normal
      AEA, and normally speaking controls, who had to detect aurally presented target
      words embedded within word lists under two conditions: silence (single task), and
      while vocalizing (dual task). To ascertain specificity of auditory-vocal deficit,
      effects of concurrent vocalizing were also examined during a visual task.
      RESULTS: Children with SM and abnormal AEA showed impaired auditory processing
      during vocalization relative to children with SM and normal AEA, and relative to
      control children. This impairment is specific to the auditory modality and does
      not reflect difficulties in dual task per se. CONCLUSIONS: The data extends
      previous findings suggesting that deficient auditory processing is involved in
      speech selectivity in SM.

PMID- 16616724
TI  - Mouse models of 22q11 deletion syndrome.
AB  - 22q11 deletion syndrome (22q11DS) is caused by an interstitial chromosomal
      microdeletion that encompasses about 40 genes. It is the most common of the
      microdeletion syndromes. The clinical phenotype, which is complex and variable,
      includes specific congenital defects of the cardiovascular system, craniofacies,
      and immune system. In early childhood, patients manifest cognitive impairment,
      behavioral disorders, and delays in motor development and language acquisition.
      Adult patients have a high risk for developing serious psychiatric disorders,
      especially schizophrenia, schizoaffective disorder, and bipolar disorder. The
      great majority of patients have an identical or near identical chromosomal
      deletion, and genotype-phenotype correlations have not been established. Indeed,
      little progress was made toward resolving the complex clinical phenotype until
      the deletion was successfully modeled in the mouse. In recent years, through a
      variety of mouse mutants that carry multigene and single gene mutations, we have
      learned that mutation in a single gene, Tbx1, is responsible for most of the
      congenital defects seen in the mouse models and in patients. We now face a
      greater challenge as we attempt to use the mouse to address the pathogenesis of
      the behavioral and psychiatric disorders associated with 22q11DS. Significant
      progress has already been made, and recent studies in the mouse suggest that
      several genes from the deleted region affect behavior and might contribute to
      disease burden in patients.

PMID- 16616725
TI  - Regional white matter and neuropsychological functioning across the adult
      lifespan.
AB  - BACKGROUND: The current study utilized magnetic resonance imaging (MRI) to more
      fully elucidate the relationship among age, regional white matter, and
      neuropsychological functioning. METHODS: One hundred ninety-nine neurologically
      healthy adults received MRI and standardized neuropsychological assessment. MR
      images were spatially normalized and segmented by tissue type; relative white
      matter values in each of the four cerebral lobes in each hemisphere were
      computed. Subjects were divided into Younger (ages 21-30), Middle (ages 31-54),
      and Older (ages 55-79) age groups. RESULTS: The Older group had significantly
      less overall relative white matter than the Middle group, who had significantly
      less overall relative white matter than the Younger participants (F (2, 193) =
      5.42, p = 0.005). Differences in frontal lobe white matter were of largest
      magnitude, followed by temporal lobe (F (6, 579) = 3.32, p = 0.003). Age and
      frontal and temporal lobe white matter were primarily associated with performance
      on neuropsychological tests of executive functioning and memory. Mediational
      analysis suggested that frontal lobe white matter mediated the relationship
      between age and performance on tasks of executive functioning and memory.
      CONCLUSIONS: The results confirm age-associated decline in frontal and temporal
      white matter, and age-related cognitive decline in several domains. Decline in
      neuropsychological functioning is, in part, mediated by a relative age-related
      reduction in frontal white matter.

PMID- 16616726
TI  - Sex differences in striatal dopamine release in healthy adults.
AB  - BACKGROUND: Sex differences in addictive disorders have been described.
      Preclinical studies have implicated the striatal dopamine system in these
      differences, but human studies have yet to substantiate these findings. METHODS:
      Using positron emission tomography (PET) scans with high-specific-activity [11C]
      raclopride and a reference tissue approach, we compared baseline striatal
      dopamine binding potential (BP) and dopamine release in men and women following
      amphetamine and placebo challenges. Subjective drug effects and plasma cortisol
      and growth hormone responses were also examined. RESULTS: Although there was no
      sex difference in baseline BP, men had markedly greater dopamine release than
      women in the ventral striatum. Secondary analyses indicated that men also had
      greater dopamine release in three of four additional striatal regions.
      Paralleling the PET findings, men's ratings of the positive effects of
      amphetamine were greater than women's. We found no sex difference in
      neuroendocrine hormone responses. CONCLUSIONS: We report for the first time a sex
      difference in dopamine release in humans. The robust dopamine release in men
      could account for increased vulnerability to stimulant use disorders and
      methamphetamine toxicity. Our findings indicate that future studies should
      control for sex and may have implications for the interpretation of sex
      differences in other illnesses involving the striatum.

PMID- 16616727
TI  - Obsessive-compulsive spectrum disorders and rheumatic fever: a family study.
AB  - BACKGROUND: Obsessive-compulsive spectrum disorders (OCSDs) are more frequent in
      patients with active or prior rheumatic fever (RF), suggesting that OCSD and RF
      may share underlying etiologic mechanisms. Our objective was to estimate the
      frequency of OCSD in first-degree relatives (FDRs) of RF patients and controls to
      determine whether there is a familial relationship between OCSD and RF. METHODS:
      This is a case-control family study. Of the 98 probands included in this study,
      31 had RF without Sydenham's chorea (SC) and had 131 relatives, 28 had RF with SC
      and had 120 relatives, and 39 were controls without RF. All probands, 87.9% of
      the RF FDRs and 93.7% of the control FDRs were assessed directly with structured
      psychiatric interviews and best-estimate diagnoses were assigned. Odds ratios of
      morbid risks were estimated using logistic regression by the generalized
      estimating equations (GEE) method and compared between groups. RESULTS: The rate
      of OCSDs was significantly higher among FDRs of RF probands than among FDRs of
      controls (n=37; 14.7% vs. n=10; 7.3%, i=.0279). A diagnosis of OCSDs in an RF
      proband was associated with a higher rate of OCSDs among FDRs when compared to
      control FDRs (p-GEE=.02). There was a trend for a higher rate of OCSDs among FDRs
      of RF probands presenting no OCSD, although the difference was not significant (p
      GEE=.09). CONCLUSION: The results are consistent with the hypothesis that a
      familial relationship exists between OCSD and RF, since an OCSD in the RF proband
      was found to increase the risk of OCSDs among FDRs. Additional neuroimmunological
      and genetic studies involving larger samples are needed to further elucidate this
      apparent familial relationship between RF and OCSD.

PMID- 16616728
TI  - Acute D2/D3 dopaminergic agonism but chronic D2/D3 antagonism prevents NMDA
      antagonist neurotoxicity.
AB  - BACKGROUND: Antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor,
      most likely by producing disinhibtion in complex circuits, acutely produce
      psychosis and cognitive disturbances in humans, and neurotoxicity in rodents.
      Studies examining NMDA Receptor Hypofunction (NRHypo) neurotoxicity in animals,
      therefore, may provide insights into the pathophysiology of psychotic disorders.
      Dopaminergic D2 and/or D3 agents can modify psychosis over days to weeks,
      suggesting involvement of these transmitter system(s). METHODS: We studied the
      ability of D2/D3 agonists and antagonists to modify NRHypo neurotoxicity both
      after a one-time acute exposure and after chronic daily exposure. RESULTS: Here
      we report that D2/D3 dopamine agonists, probably via D3 receptors, prevent NRHypo
      neurotoxicity when given acutely. The protective effect with D2/D3 agonists is
      not seen after chronic daily dosing. In contrast, the antipsychotic haloperidol
      does not affect NRHypo neurotoxicity when given acutely at D2/D3 doses. However,
      after chronic daily dosing of 1, 3, or 5 weeks, haloperidol does prevent NRHypo
      neurotoxicity with longer durations producing greater protection. CONCLUSIONS:
      Understanding the changes that occur in the NRHypo circuit after chronic exposure
      to dopaminergic agents could provide important clues into the pathophysiology of
      psychotic disorders.

PMID- 16616729
TI  - The association between C-reactive protein levels and depression: Results from
      the northern Finland 1966 birth cohort study.
AB  - BACKGROUND: To investigate whether depressive episodes (previous, current single,
      and recurrent) are associated in both genders with highly sensitive C-reactive
      protein (hs-CRP) levels, earlier recommended for risk assessment of
      cardiovascular disease. The impact of the severity of current single and
      recurrent depressive episodes on this putative association was also investigated.
      METHODS: The genetically homogeneous Northern Finland 1966 Birth Cohort was
      followed until age 31, when, in a cross-sectional setting (n = 5269), the highly
      sensitive enzyme immunoassay (hs-EIA) method was used to measure CRP
      concentration. Depressive episodes were defined through mailed questionnaires,
      including Hopkins Symptom Checklist-25 (HSCL-25) and information on self
      reported, doctor-diagnosed depression. RESULTS: After adjusting for confounders,
      logistic regression analyses showed that in male subjects, elevated hs-CRP levels
      (> or =1.0 mg/L) increased the probability for severe current and recurrent
      depressive episodes 1.7-fold and 3.1-fold, respectively. Correspondingly, an hs
      CRP level of >3.0 mg/L increased the probability for recurrent depression up to
      4.1-fold. In female subjects, no statistically significant associations were
      found. CONCLUSIONS: Our results support the hypothesis that an activation of
      systemic inflammatory processes may contribute to the pathophysiology of severe
      depression in men. Further investigations are needed regarding the impact of our
      findings on diagnostic/treatment strategies concerning severe and, especially
      recurrent, depression in men.

PMID- 16616730
TI  - A single nucleotide polymorphism at DBH, possibly associated with attention
      deficit/hyperactivity disorder, associates with lower plasma dopamine beta
      hydroxylase activity and is in linkage disequilibrium with two putative
      functional single nucleotide polymorphisms.
AB  - BACKGROUND: The DBH gene regulates plasma dopamine beta-hydroxylase activity
      (pDbetaH). Two single nucleotide polymorphisms (SNPs), -1021C-->T (rs1611115;
      SNP1) and +1603C-->T (rs6271; SNP3), independently influence pDbetaH. Another
      SNP, commonly known as DBH Taq1A (rs2519152; SNP2) is associated with attention
      deficit/hyperactivity disorder (ADHD) in some (but not all) studies. We tested
      whether 1) SNP2 associates with pDbetaH; and 2) whether linkage disequilibrium
      (LD) between SNP2 and the other SNPs explains that association. METHODS: Plasma
      dopamine beta-hydroxylase activity and genotypes at the SNPs were determined in
      Caucasian subjects (n = 418). Associations to pDbetaH were examined using
      analyses of variance (ANOVAs) and LD among the SNPs using estimation
      maximization. RESULTS: 1) Each polymorphism analyzed alone associated with
      pDbetaH; 2) SNP2 was in strong LD with SNP1 and SNP3, respectively, but there was
      no significant LD between SNP1 and SNP3; and 3) analyzed jointly, each SNP
      contributed significantly and uniquely to plasma DbetaH activity. CONCLUSIONS: 1)
      SNP2 associates with pDbetaH; 2) SNP2 shows LD with SNP1 and SNP3; 3) most of the
      association between SNP2 and pDbetaH simply reflects that LD; however, 4) SNP2
      also appears to exert a small independent effect on pDbetaH, suggesting that
      SNP2, or another variant in LD with it, uniquely influences pDbetaH.

PMID- 16616731
TI  - Contextual and temporal modulation of extinction: behavioral and biological
      mechanisms.
AB  - Extinction depends, at least partly, on new learning that is specific to the
      context in which it is learned. Several behavioral phenomena (renewal,
      reinstatement, spontaneous recovery, and rapid reacquisition) suggest the
      importance of context in extinction. The present article reviews research on the
      behavioral and neurobiological mechanisms of contextual influences on extinction
      learning and retrieval. Contexts appear to select or retrieve the current
      relationship of the conditional stimulus (CS) with the unconditional stimulus
      (US), and they are provided by physical background cues, interoceptive drug cues,
      emotions, recent trials, and the passage of time. The current article pays
      particular attention to the effects of recent trials and trial spacing. Control
      of fear extinction by physical context involves interactions between the dorsal
      hippocampus and the lateral nucleus of the amygdala. This interaction may be
      mediated by gamma-aminobutyric acid (GABA)-ergic and adrenergic mechanisms.

PMID- 16616732
TI  - Activity-dependent heterogeneous populations of nitric oxide synthase neurons in
      the rat dorsal raphe nucleus.
AB  - The brainstem dorsal raphe nucleus (DRN) contains an abundant distribution of
      nitric oxide (NO) synthase (NOS)-containing neuronal profiles in two distinct
      populations: faint- and intense-immunoreactive cells in midline (ventromedial and
      dorsomedial) and lateral wing subregions, respectively. This study tested the
      hypothesis that different functional dynamics underlie the topography of NOS
      containing cells in the DRN rostrocaudal and mediolateral neuraxis by using a
      capsaicin challenge paradigm (50 mg/kg, subcutaneous). Compared with vehicle,
      capsaicin significantly and preferentially increased nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d, an index of constitutive NOS)
      reactivity in the rostral midline and caudal lateral wing subregions.
      Furthermore, capsaicin activated more Fos-positive cells than vehicle within all
      subregions of the DRN but with a caudal versus rostral predominance in activation
      pattern. In addition, a high proportion of capsaicin-induced Fos cells in the
      midline but almost none in lateral wing stained for NADPH-d. These observations
      suggest the existence of two functionally distinct populations of NOS neurons in
      the DRN. Furthermore, capsaicin increased galanin immunoreactivity with
      predominant staining in cell soma and fiber processes in midline and lateral wing
      subregions of the nucleus, respectively. The total capsaicin-induced galanin
      immunoreactivity was higher in rostral versus caudal DRN, and a high proportion
      of galanin-positive cells in the midline also contained NADPH-d and neuronal NOS,
      thus suggesting a potential NO-galanin interaction in these neurons. The
      differential pattern of Fos/NADPH-d colocalization across the nucleus suggests
      that midline and lateral wing NOS neurons of the DRN express their
      neuromodulatory actions on discrete efferent targets via different intracellular
      mechanisms.

PMID- 16616733
TI  - The effect of descending theta rhythmic input from the septohippocampal system on
      firing in the supramammillary nucleus.
AB  - The supramammillary nucleus (SUM) is part of an ascending pathway conveying
      behavior-dependent drive to the septal generator of limbic theta rhythm. The SUM
      is, however, reciprocally connected to the septohippocampal system and there is
      strong evidence that both septum and SUM are capable of generating theta rhythmic
      activity. The present study examined the possible role of a descending rhythmic
      input to the SUM using simultaneously recorded hippocampal EEG and SUM neuronal
      activity in anesthetized rats. Fourier based phase analysis was performed on
      recordings in which fast theta rhythmic activity was elicited by tail pinch and
      in which a slower theta rhythm persisted after cessation of the sensory stimulus.
      It was found that the firing of a subpopulation of SUM neurons followed the
      hippocampal theta waves with a constant time delay, rather than a constant phase,
      suggesting that during deceleration associated with a shift from sensory-elicited
      theta to spontaneous theta rhythm they followed a descending rhythmic input, most
      likely from the medial septum. Neurons of a second group, which fired at the
      hippocampal theta peaks, did not show such relationship demonstrating
      heterogeneity in the population of rhythmic SUM neurons and their possible roles
      in theta generation. Combined with previous studies focusing on the role of the
      ascending theta drive from the SUM, these results demonstrate dynamic
      bidirectional coupling between subcortical theta generators. Thus, during certain
      states, rhythmically firing SUM neurons lead the septal theta oscillator, in
      others the direction may reverse and SUM follows a theta drive of septal origin.

PMID- 16616734
TI  - Prospective identification and purification of hair cell and supporting cell
      progenitors from the embryonic cochlea.
AB  - Expression of the cyclin-dependent kinase inhibitor p27(Kip1) defines a post
      mitotic population of cells in the embryonic mammalian cochlea that constitutes
      the nascent organ of Corti. Here, we describe techniques to purify these
      precursors using a transgenic p27/GFP reporter and fluorescence activated cell
      sorting (FACS). We demonstrate that these cells express other markers of the
      sensory lineage, such as Sox2, and when placed in dissociated cell culture
      differentiate as hair cells and supporting cells. The purified sensory
      progenitors thus obtained provide a means of studying the process of hair cell
      and supporting cell differentiation in vitro, as well as providing a means of
      analyzing the molecular and physiological properties of this unique population of
      cells.

PMID- 16616735
TI  - A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and
      fever-induced ventricular fibrillation.
AB  - OBJECTIVE: Brugada syndrome (BS) is an inherited electrical cardiac disorder
      characterized by right bundle branch block pattern and ST segment elevation in
      leads V1 to V3 on surface electrocardiogram that can potentially lead to
      malignant ventricular tachycardia and sudden cardiac death. About 20% of patients
      have mutations in the only so far identified gene, SCN5A, which encodes the alpha
      subunit of the human cardiac voltage-dependent sodium channel (hNa(v)1.5). Fever
      has been shown to unmask or trigger the BS phenotype, but the associated
      molecular and the biophysical mechanisms are still poorly understood. We report
      on the identification and biophysical characterization of a novel heterozygous
      missense mutation in SCN5A, F1344S, in a 42-year-old male patient showing the BS
      phenotype leading to ventricular fibrillation during fever. METHODS: The mutation
      was reproduced in vitro using site-directed mutagenesis and characterized using
      the patch clamp technique in the whole-cell configuration. RESULTS: The
      biophysical characterization of the channels carrying the F1344S mutation
      revealed a 10 mV mid-point shift of the G/V curve toward more positive voltages
      during activation. Raising the temperature to 40.5 degrees C further shifted the
      mid-point activation by 18 mV and significantly changed the slope factor in
      Na(v)1.5/F1344S mutant channels from -6.49 to -10.27 mV. CONCLUSIONS: Our
      findings indicate for the first time that the shift in activation and change in
      the slope factor at a higher temperature mimicking fever could reduce sodium
      currents' amplitude and trigger the manifestation of the BS phenotype.

PMID- 16616736
TI  - Cancer gene search with data-mining and genetic algorithms.
AB  - Cancer leads to approximately 25% of all mortalities, making it the second
      leading cause of death in the United States. Early and accurate detection of
      cancer is critical to the well being of patients. Analysis of gene expression
      data leads to cancer identification and classification, which will facilitate
      proper treatment selection and drug development. Gene expression data sets for
      ovarian, prostate, and lung cancer were analyzed in this research. An integrated
      gene-search algorithm for genetic expression data analysis was proposed. This
      integrated algorithm involves a genetic algorithm and correlation-based
      heuristics for data preprocessing (on partitioned data sets) and data mining
      (decision tree and support vector machines algorithms) for making predictions.
      Knowledge derived by the proposed algorithm has high classification accuracy with
      the ability to identify the most significant genes. Bagging and stacking
      algorithms were applied to further enhance the classification accuracy. The
      results were compared with that reported in the literature. Mapping of genotype
      information to the phenotype parameters will ultimately reduce the cost and
      complexity of cancer detection and classification.

PMID- 16616737
TI  - FGF10 is required for cell proliferation and gland formation in the stomach
      epithelium of the chicken embryo.
AB  - The development of digestive organs in vertebrates involves active epithelial
      mesenchymal interactions. In the chicken proventriculus (glandular stomach), the
      morphogenesis and cytodifferentiation of the epithelium are controlled by the
      inductive signaling factors that are secreted from the underlying mesenchyme.
      Previous studies have shown that Fgf10 is expressed in the developing chicken
      proventricular mesenchyme, whereas its receptors are present in the epithelium.
      In our present study, we show that FGF10 is an early mesenchymal signal that is
      critically associated with the developmental processes in the proventricular
      epithelium. Furthermore, virus-mediated Fgf10 overexpression in ovo results in a
      hypermorphic epithelial structure and an increase in epithelial cell number. In
      contrast, the overexpression of a secreted FGFR2b (sFGFR2b), an FGF10 antagonist,
      blocks cell proliferation and gland formation in the proventricular epithelium in
      ovo. This downregulation of proliferative activity was subsequently found to
      retard gland formation and also to delay differentiation of the epithelium. These
      results demonstrate that FGF10 signaling, mediated by FGFR1b and/or FGFR2b, is
      required for proliferation and gland formation in the epithelium in the
      developing chick embryo.

PMID- 16616739
TI  - Thresholds for activation of rabbit retinal ganglion cells with a subretinal
      electrode.
AB  - The ultimate success of a retinal prosthesis to create vision will likely depend
      upon developing a base of knowledge of how best to electrically stimulate the
      retina. Previously, we studied the responses of rabbit retinal ganglion cells
      (RGCs) to current pulses applied with an electrode placed on the epiretinal
      surface. In the present study, we examined the responses of rabbit RGCs to
      current pulses applied with a subretinal electrode. Single-unit extracellular
      recordings were made from OFF RGCs and ON RGCs in isolated retinas, which were
      stimulated with monophasic current pulses (0.1-50ms in duration), delivered
      through a 500-mum diameter electrode. All RGCs elicited one or more bursts of
      action potentials upon electrical stimulation of the retina. The timing of the
      bursts depended upon both the polarity of the electrical stimulus and the RGC
      type. With near-threshold current pulses, the response latencies of OFF RGCs to
      anodal stimulation were comparable to those of ON RGCs to cathodal stimulation,
      whereas the response latencies of OFF RGCs to cathodal stimulation were
      comparable to those of ON RGCs to anodal stimulation. Threshold currents for
      activation of RGCs decreased with increased pulse duration. For OFF RGCs,
      threshold currents for cathodal current pulses were, on average, 2-7.5 times
      higher (depending upon pulse duration) than the threshold currents for anodal
      current pulses. For ON RGCs, threshold currents for cathodal and anodal current
      pulses were, on average, nearly identical for all pulse durations and were
      equivalent to threshold currents of OFF RGCs to anodal stimulation. With respect
      to a subretinal prosthesis, our findings suggest the possibility that cathodal
      current pulses may bias activation of ON RGCs in blind patients.

PMID- 16616738
TI  - The roles of wingless and decapentaplegic in axis and appendage development in
      the red flour beetle, Tribolium castaneum.
AB  - Axis patterning and appendage development have been well studied in Drosophila
      melanogaster, a species in which both limb and segment morphogenesis are derived.
      In Drosophila, positional information from genes important in anteroposterior and
      dorsoventral axis formation, including wingless (wg) and decapentaplegic (dpp),
      is required for allocating and patterning the appendage primordia. We used RNA
      interference to characterize the functions of wg and dpp in the red flour beetle,
      Tribolium castaneum, which retains more ancestral modes of limb and segment
      morphogenesis. We also characterized the expression of potential targets of the
      WG and DPP signaling pathways in these embryos. Tribolium embryos in which dpp
      had been downregulated had defects in the dorsalmost body wall, but did not
      appear to have been globally repatterned and had normal appendages.
      Downregulation of wg led to the loss of segment boundaries, gnathal and thoracic
      appendages, and lateral head lobes, and to changes in the expression of dpp,
      Distal-less, and Engrailed. The functions of wg varied along both the
      anteroposterior and dorsoventral axes of the embryo. Phylogenetic comparisons
      indicate that the role of WNT signaling in segment boundary formation is
      evolutionarily old, but that its role in appendage allocation originated in the
      common ancestor of holometabolous insects.

PMID- 16616740
TI  - Focus on molecules: ezrin.

PMID- 16616741
TI  - Differences in leukocyte phenotype and interferon-gamma expression in stroma and
      endothelium during corneal graft rejection.
AB  - Critical to the success of human corneal transplants is prevention of corneal
      endothelial rejection, yet little is known about the endothelial infiltrate. To
      examine the endothelium, a method for removal and processing this layer as a flat
      sheet was used and the infiltrate was compared with stroma and epithelium. LEW or
      PVG strain rat corneas were transplanted to PVG strain recipients. Clinical
      changes after transplantation were monitored by slit lamp and animals sacrificed
      at a range of time points during rejection. Clinically defined rejection,
      accompanied by an epithelial rejection line and endothelial cell infiltration,
      occurred between days 10 and 15. There was some infiltration of leukocytes in the
      stroma of isografts at these time points, but significantly more in allografts
      (p<0.003 for all subsets). There was no infiltration of isograft endothelium at
      any time and no infiltration of allograft endothelium on day 10. On day 15, there
      were similar numbers of all major subsets except B cells in the stroma, while on
      the endothelium macrophages, MHC class II(+) cells and CD8(+) cells predominated
      (p<0.001 CD4(+) vs CD8(+) cells). T cells and NK cells predominated in the
      epithelial rejection line. While TNF-alpha and IFN-gamma-producing cells were
      numerous in stroma and epithelium, no IFN-gamma-producing cells were found on
      endothelium. Distinct differences in infiltrative profile within layers of the
      cornea suggest that the mechanisms of rejection may also differ. The restricted
      endothelial cell profile and lack of IFN-gamma suggests that the anti-endothelial
      response may be modulated by the anterior chamber environment.

PMID- 16616742
TI  - First successful pregnancy outcome after preimplantation genetic diagnosis for
      aneuploidy screening in embryos generated from natural-cycle in vitro
      fertilization combined with an in vitro maturation procedure.
AB  - OBJECTIVE: To report on the first successful pregnancy performing preimplantation
      genetic diagnosis (PGD) on embryos obtained after combining natural IVF with in
      vitro maturation procedure. DESIGN: Case report. SETTING: University hospital.
      PATIENT(S): A 35-year-old patient with polycystic ovaries who was attending the
      fertility clinic. INTERVENTION(S): In vitro maturation of immature oocytes and
      preimplantation genetic diagnosis. MAIN OUTCOME MEASURE(S): Preimplantation
      genetic diagnosis of aneuploidy screening in embryos produced from in vitro
      maturation procedure. RESULT(S): Thirteen immature and two mature oocytes were
      collected, and eight mature oocytes were normally fertilized, of which six
      embryos were biopsied for chromosome analysis. Two chromosomally normal embryos
      were transferred on day 5, resulting in the birth of a healthy child.
      CONCLUSION(S): This case report demonstrates that an acceptable number of embryos
      can be generated after in vitro maturation procedure to perform PGD for
      aneuploidy screening and that this approach can be extended to patients with
      polycystic ovaries or polycystic ovary syndrome who are undergoing PGD for other
      genetic diseases.

PMID- 16616743
TI  - Levels of P34H, a sperm protein of epididymal origin, as a predictor of
      conventional in vitro fertilization outcome.
AB  - A prospective double-blind study was performed to determine if Western blot
      detection of P34H, a sperm protein of epididymal origin that is involved in the
      binding to the zona pellucida, is predictive of standard IVF outcome. Our results
      demonstrate that the proportion of positive P34H cases that produced embryos in
      vitro clearly differs from cases with undetectable levels of P34H (P<.001).

PMID- 16616744
TI  - Novel serum inflammatory markers in patients with adnexal mass who had surgery
      for ovarian torsion.
AB  - OBJECTIVE: To determine the diagnostic value of preoperative levels of
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL
      8), and E-selectin in patients with an adnexal mass who had surgery for ovarian
      torsion. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S):
      Fifty consecutive women with adnexal mass who were admitted with a diagnosis of
      ovarian torsion. INTERVENTION(S): All had a single preoperative measurement of IL
      6, IL-8, TNF-alpha, and E-selectin by ELISA. MAIN OUTCOME MEASURE(S): To
      determine if a single preoperative serum sampling of IL-6, IL-8, TNF-alpha, and E
      selectin by ELISA can diagnose ovarian torsion. RESULT(S): Thirteen patients had
      proven torsion of the ovary. Serum levels of IL-6 were significantly higher in
      the 13 patients with proven ovarian torsion compared with the 37 without ovarian
      torsion. Patients with IL-6 serum values > or =10.2 pg/mL had a 16 times higher
      risk of having ovarian torsion. No significant difference was found in TNF-alpha,
      IL-8, and E-selectin between the two groups. CONCLUSION(S): The IL-6 levels might
      assist in the prompt diagnosis of ovarian torsion and allow a timely surgical
      intervention.

PMID- 16616745
TI  - Serum anti-mullerian hormone levels in women with secondary amenorrhea.
AB  - Anti-mullerian hormone (AMH) appears to regulate follicular growth. The aim of
      this study was to investigate AMH serum levels in patients affected by secondary
      amenorrhea. The AMH was significantly lower (or undetectable) in patients with
      premature ovarian failure (POF) and significantly higher in patients affected by
      polycystic ovary syndrome (PCOS). We suggest that serum AMH evaluation could be
      associated with that of established hormones, such as FSH, LH, and E2, when the
      activity of hypothalamo-pituitary-ovarian axis is investigated.

PMID- 16616746
TI  - Macrophage migration inhibitory factor expression in the intrauterine endometrium
      of women with endometriosis varies with disease stage, infertility status, and
      pelvic pain.
AB  - OBJECTIVE: To evaluate the concentrations of macrophage migration inhibitory
      factor (MIF) in the eutopic endometrial tissue of women with and without
      endometriosis. DESIGN: Retrospective study using ELISA to measure MIF
      concentrations in total endometrial tissue proteins extracts. SETTING: Gynecology
      clinic and human reproduction research laboratory. PATIENT(S): Forty-five women
      with endometriosis and 25 normal women. INTERVENTION(S): Endometrial biopsies
      were obtained a few days before laparoscopy. MAIN OUTCOME MEASURE(S):
      Concentrations of MIF in tissue protein extracts. RESULT(S): Levels of MIF were
      significantly higher in women with endometriosis, increased with disease stage,
      and were cycle phase dependent. Of note is the significant increase in MIF levels
      occurring in the midsecretory phase in women with endometriosis as compared with
      controls, particularly in infertile patients, as well as in the late secretory
      phase preceding menstruation. Furthermore, MIF levels seemed to be particularly
      elevated in women with endometriosis who were infertile and who suffered from
      pelvic pain. CONCLUSION(S): This study showed a significant increase in MIF
      concentrations in the intrauterine endometrial tissue of women with
      endometriosis, occurring at specific phases of the menstrual cycle, a
      relationship between MIF concentrations and disease stage, and a possible role
      for this factor in endometriosis-associated pain and infertility.

PMID- 16616747
TI  - Adult onset of declining spermatogenesis in a man with nonmosaic Klinefelter's
      syndrome.
AB  - OBJECTIVE: To examine an unusual case of Klinefelter's syndrome. DESIGN: Case
      report. SETTING: An infertility clinic at a private hospital. PATIENT(S): A
      patient with nonmosaic Klinefelter's syndrome who had had a child with his ex
      wife without artificial reproductive technologies. INTERVENTION(S): Karyotyping
      with peripheral blood lymphocytes, microdissection testicular sperm extraction,
      and intracytoplasmic sperm injection (ICSI). MAIN OUTCOME MEASURE(S): Sperm count
      and testicular histopathology. RESULT(S): Semen analysis revealed severe
      oligoasthenozoospermia. Intracytoplasmic sperm injection using ejaculated
      spermatozoa was performed, and successful pregnancy and delivery were achieved.
      Two years later, multiple semen analyses revealed azoospermia. Microdissection
      testicular sperm extraction was performed, and motile sperm were successfully
      retrieved. Unfortunately, the first cycle of ICSI using testicular sperm failed.
      Testicular histopathology was compatible with decreased spermatogenesis.
      CONCLUSION(S): This is a case of a man with nonmosaic Klinefelter's syndrome who
      exhibited progressive decline of spermatogenesis. This case suggests the merit of
      early sperm retrieval and cryopreservation for future management of infertility
      in Klinefelter's syndrome.

PMID- 16616748
TI  - Effect of acupuncture on the outcome of in vitro fertilization and
      intracytoplasmic sperm injection: a randomized, prospective, controlled clinical
      study.
AB  - OBJECTIVE: To determine the effect of luteal-phase acupuncture on the outcome of
      IVF/intracytoplasmic sperm injection (ICSI). DESIGN: Randomized, prospective,
      controlled clinical study. SETTING: University IVF center. PATIENT(S): Two
      hundred twenty-five infertile patients undergoing IVF/ICSI. INTERVENTION(S): In
      group I, 116 patients received luteal-phase acupuncture according to the
      principles of traditional Chinese medicine. In group II, 109 patients received
      placebo acupuncture. MAIN OUTCOME MEASURE(S): Clinical and ongoing pregnancy
      rates. RESULT(S): In group I, the clinical pregnancy rate and ongoing pregnancy
      rate (33.6% and 28.4%, respectively) were significantly higher than in group II
      (15.6% and 13.8%). CONCLUSION(S): Luteal-phase acupuncture has a positive effect
      on the outcome of IVF/ICSI.

PMID- 16616749
TI  - Fathers over 40 and increased failure to conceive: the lessons of in vitro
      fertilization in France.
AB  - OBJECTIVE: To investigate paternal age effect mediated by biological
      modifications with use of data from assisted reproductive technologies. DESIGN:
      National IVF registry. SETTING: Fifty nine French IVF centers. PATIENT(S): A
      total of 1,938 men whose partners were totally sterile, with bilateral tubal
      obstruction or absence of both tubes (to avoid bias sampling in analysis of
      paternal age) and treated by conventional IVF. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Risk of failure to conceive defined as absence of
      intrauterine pregnancy. RESULT(S): The odds ratio of failure to conceive for
      paternal age > or =40 years was 2.00 (95% confidence interval [CI]: 1.10-3.61)
      when the woman was 35-37 years old, 2.03 (95% CI: 1.12-3.68) for age 38-40 years,
      and 5.74 (95% CI: 2.16, 15.23) for age 41 years and over. CONCLUSION(S): As an
      increasing number of couples choose to postpone childbearing, they should be
      informed that paternal age over 40 years is an important risk factor for failure
      to conceive.

PMID- 16616751
TI  - It is apparent that there has been a paradigm shift in the evaluation and funding
      of research. Interview by Dr. Rae Silver.

PMID- 16616752
TI  - Transcriptomics and proteomics: advancing the understanding of genetic basis of
      fracture healing.
AB  - Fracture healing is a complex physiological post-natal process, which involves
      the coordination of several different cell types. Exploring the orchestration of
      events and the simultaneous activation of osteogenesis and chondrogenesis that
      recapitulates mammalian embryological skeletal development seems to be not only
      sophisticated but also challenging. A large number of genes involved in the above
      process are known, but many more remain to be discovered. The functional
      characterisation of these genes promises to elucidate the repair process as well
      as skeletal abnormalities and aging. We here review the current knowledge on
      early and late gene expression during fracture healing, the genes so far
      associated with osteoblast and osteoclast differentiation, the BMP antagonists,
      and the Wnts signalling pathway.

PMID- 16616753
TI  - Wound healing: immunological aspects.
AB  - Wound healing is a complex biological process, comprised of a series of a
      sequential events aiming to repair injured tissue. The role of the immune system
      in this process is not only to recognise and combat the newly presented antigens
      at the site of injury, but also to participate in the debridement of the damaged
      area and to contribute to the process of healing. In this review, we discuss the
      molecules and cells of the immune system that participate in tissue repair. We
      describe the mechanisms of immune recognition during initial insult and the
      innate and adaptive immune responses to injury. Finally, we address the role of
      the immune system in regeneration and repair.

PMID- 16616754
TI  - The role of inhibitory molecules in fracture healing.
AB  - The balance between all the signalling molecules involved in bone formation with
      their inhibitors and most importantly between BMPs and their antagonists is
      critical determinant of osteogenesis, and therefore of skeletal development,
      fracture repair, and bone remodelling. The main identified inhibitory molecules
      of the osteogenic lineage, either from studies during embryonic development or
      from in vitro and in vivo studies are presented in the herein study. Potential
      treatments using these molecules either alone or in combination with BMPs to
      control the bone growth and overgrowth are already under investigation aiming in
      treatments that mimic as much as possible the natural process of bone generation
      in various situations including fracture healing, osteoporosis, and
      osteoarthritis and other metabolic disorders, in order to more closely resemble
      the original tissue.

PMID- 16616756
TI  - A comparison of the NCEP-ATPIII, IDF and AHA/NHLBI metabolic syndrome definitions
      with relation to early carotid atherosclerosis in subjects with
      hypercholesterolemia or at risk of CVD: evidence for sex-specific differences.
AB  - The metabolic syndrome is associated with increased risk of cardiovascular
      disease. However, the association between metabolic syndrome and atherosclerosis
      in hypercholesterolemic patients remains unknown. We examined the association
      between carotid atherosclerosis and metabolic syndrome definitions using the NCEP
      ATPIII, International Diabetes Federation (IDF) and American Heart
      Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definitions in
      1782 subjects at risk of cardiovascular disease including 926 with
      hypercholesterolemia (LDL cholesterol > or =160 mg/dL; mean=203 mg/dL).
      Irrespective of definition, carotid intima-media thickness was significantly
      higher in both men and women diagnosed with the MetS compared to those without
      MetS. This relationship persists in males with hypercholesterolemia,
      independently of LDL cholesterol level. Regression analyses, both unadjusted and
      adjusted for traditional risk factors, indicate that in males the AHA/NHLBI
      definition, and in females the IDF definition are the strongest predictors of
      carotid atherosclerosis. These results highlight important gender differences
      that exist in the current clinical definitions of the metabolic syndrome, with
      regards to predicting early atherosclerotic lesions. In addition, this study
      shows that in males with hypercholesterolemia, MetS is independently associated
      with increased atherosclerosis, supporting screening for MetS among people at
      risk of CVD.

PMID- 16616757
TI  - Adjustments to McConville et al. and Young et al. body segment inertial
      parameters.
AB  - Body segment inertial parameters (BSIPs) are important data in biomechanics. They
      are usually estimated from predictive equations reported in the literature.
      However, most of the predictive equations are ambiguously applicable in the
      conventional 3D segment coordinate systems (SCSs). Also, the predictive equations
      reported in the literature all include two assumptions: the centre of mass and
      the proximal and distal endpoints are assumed to be aligned, and the inertia
      tensor is assumed to be principal in the segment axes. These predictive
      equations, restraining both position of the centre of mass and orientation of the
      principal axes of inertia, become restrictive when computing 3D inverse dynamics,
      when analyzing the influence of BSIP estimations on joint forces and moments and
      when evaluating personalized 3D BSIPs obtained from medical imaging. In the
      current study, the extensive data from McConville et al. (1980. Anthropometric
      relationships of body and body segment moments of inertia. AFAMRL-TR-80-119,
      Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, Dayton,
      Ohio) and from Young et al. (1983. Anthropometric and mass distribution
      characteristics of the adults female. Technical Report AFAMRL-TR-80-119, FAA
      Civil Aeromedical Institute, Oklaoma City, Oklaoma) are adjusted in order to
      correspond to joint centres and to conventional segment axes. In this way,
      scaling equations are obtained for both males and females that provide BSIPs
      which are directly applicable in the conventional SCSs and do not restrain the
      position of the centre of mass and the orientation of the principal axes. These
      adjusted scaling equations may be useful for researchers who wish to use
      appropriate 3D BSIPs for posture and movement analysis.

PMID- 16616758
TI  - Modelling migration behavior of peptide hormones in capillary electrophoresis
      electrospray mass spectrometry.
AB  - The applicability in capillary electrophoresis-electrospray mass spectrometry (CE
      ESI-MS) of the classical semiempirical relationships between electrophoretic
      mobility and charge-to-mass ratio (me versus q/Malpha) has been investigated in
      order to describe the migration behavior of a series of bioactive peptide
      hormones. The influence upon the models of the separation electrolyte pH and the
      accuracy of the pK values of these compounds were studied first by capillary
      electrophoresis with ultraviolet detection (CE-UV). The classical polymer model,
      alpha = 1/2, resulted in slightly better correlations at any of the studied pH.
      Furthermore, a general linear equation can be adjusted combining all the
      experimental data pairs, which suggests that correlation in the whole pH range is
      independent of the ionic form of the studied peptide hormones. The plots of
      q/M1/2 against separation electrolyte pH were used to predict their
      electrophoretic separations, using the accurate pK values obtained in a previous
      work by CE-UV for charge calculations. A volatile separation electrolyte
      containing 50 mM of acetic acid and 50 mM of formic acid at pH 2.85 was selected
      for optimum CE-UV and CE-ESI-MS analysis of the peptide mixture. At this pH and
      taking into account the specific features of the coupling, the correlation using
      the classical polymer law was excellent and its parameters were similar to the
      ones of the general linear equation previously obtained by CE-UV. This confirmed
      the applicability in CE-ESI-MS of the semiempirical relationship originally
      established by CE-UV.

PMID- 16616759
TI  - Influence of the extraction methodology on the analysis of polycyclic aromatic
      hydrocarbons in pasture vegetation.
AB  - Pasture vegetation plays an important role in the air-surface exchange and food
      chain transfer of polycyclic aromatic hydrocarbons (PAHs). Therefore,
      considerable research has been focused towards measuring PAHs in vegetation using
      different analytical methods. However, in most cases information on the
      efficiencies of the different extraction methods employed is missing. This
      complicates data interpretation and inter-study comparisons. To address this
      deficiency, the extraction efficiencies of two commonly used pasture vegetation
      extraction techniques (sonication and soxhlet) and different solvents (hexane,
      DCM and hexane:acetone [4:1, v/v]) were compared. The completeness of the
      extraction was investigated using alkaline saponification in methanol. Soxhlet
      extraction was able to access between 60 and 90% of the total amount of PAHs in
      the pasture vegetation. Sonication was less efficient, only being able to extract
      between 10 and 50% of the PAHs. Extraction efficiencies were found to increase
      with increasing PAH molecular weight. The implications of these findings on data
      interpretation are discussed.

PMID- 16616760
TI  - Isolation of bovine lactoferrin, lactoperoxidase and enzymatically prepared
      lactoferricin from proteolytic digestion of bovine lactoferrin using adsorptive
      membrane chromatography.
AB  - A new downstream procedure for the isolation of bovine lactoferrin (bLf),
      lactoperoxidase and bovine lactoferricin (LfcinB) from sweet cheese whey was
      developed at the laboratory scale, based on membrane adsorber technology. The
      procedure was upscaled later on to an industrially relevant scale for the
      purificationof sweet whey concentrate with a recovery yield for lactoferrin of
      more than 90%. Based on these results the industrial process for 1 x 10(8) kg
      whey per year was projected. These high-value proteins were downstreamed by using
      cation-exchange membrane systems (Sartobind S, Sartorius, Gottingen, Germany).
      These strongly acidic membranes trap proteins in its anionic form. The dynamic
      loading capacity for both proteins as well as the optimal elution profiles with
      sodium chloride gradients were derived from laboratory experiments using membrane
      modules with 15-75 cm2 membrane material. Further investigations were performed
      with 1 m2 modules in a continuous process mode. The enzymatic preparation of
      LfcinB from bLf was performed by pepsin hydrolysis and the isolation of LfcinB
      was directly carried out from the enzymatic digest mixture. The identification of
      the proteins was performed with matrix-assisted laser desorption ionisation mass
      spectrometry (MALDI-MS). LfcinB and bLf were both tested afterwards in biological
      assays in order to show not only the efficiency of the downstreaming process in
      regard to product quantity but also to product quality (biological activity).

PMID- 16616762
TI  - Neutrophil depletion reduces myocardial apoptosis and attenuates NFkappaB
      activation/TNFalpha release after ischemia and reperfusion.
AB  - BACKGROUND: This study tested the hypothesis that depletion of neutrophils (PMNs)
      reduces myocardial apoptosis via reducing oxidant generation and inhibiting
      NFkappaB-mediated signaling pathways after ischemia/reperfusion. METHODS:
      Anesthetized rats were randomly divided into one of four groups: CONTROL: 30 min
      ischemia and 3 h of reperfusion; PMN depletion: anti-PMN serum was injected 6 h
      before ischemia; N-acetylcysteine (NAC): NAC was given twice before ischemia and
      at reperfusion. Sham: the ligature was placed without coronary occlusion.
      Apoptosis was detected by TUNEL staining and DNA fragmentation. PMN accumulation
      was studied by immunohistochemical staining. Levels of TNF-alpha, IL-6, and
      caspase-3 were detected by Elisa kits. Expression in NFkappaB, Bcl-2, and Bax was
      assessed by Western blotting analysis. RESULTS: Relative to CONTROL, depletion of
      PMNs or NAC treatment reduced levels of plasma TNFalpha (567 +/- 130* and 231 +/-
      72* versus 1994 +/- 447 pg/ml) and IL-6 (791 +/- 473* and 666 +/- 300* versus
      3724 +/- 1233, pg/ml), accompanying a reduction in PMN accumulation (12 +/- 1*
      and 13 +/- 0.6* versus 20 +/- 1 mm2 myocardium) in ischemic myocardium. Both
      groups showed a reduction in expression of nuclear NFkappaB relative to CONTROL
      (62 +/- 9* and 67 +/- 8* versus 124 +/- 16 arb.u), consistent with reduced
      NFkappaB binding activity. The number of apoptotic cells (%) in area at risk
      myocardium was comparably reduced in anti-PMN and NAC groups relative to CONTROL
      (12 +/- 1* and 14 +/- 0.9* versus 20 +/- 1), consistent with reduced appearance
      of DNA ladders. Furthermore, activated caspase-3 was significantly reduced and
      Bcl-2 was increased relative to CONTROL. No difference in all parameters measured
      was detected during the course of experiment in the Sham group. CONCLUSION: These
      data suggest that the oxidants generated from activated PMNs after
      ischemia/reperfusion trigger myocardial apoptosis, which is further supported by
      an anti-oxidant therapy with NAC, potentially mediated by enhanced NFkappaB
      TNFalpha signaling pathway, activated caspase-3 and down-regulated Bcl-2. *P <
      0.05 versus CONTROL.

PMID- 16616763
TI  - Effects of hydroxyethyl starch 130/0.4 on pulmonary capillary leakage and
      cytokines production and NF-kappaB activation in CLP-induced sepsis in rats.
AB  - BACKGROUND: Sepsis and resulting multiple system organ failure are the leading
      causes of mortality in intensive care units. Hydroxyethyl starch (HES) 130/0.4
      was a novel preparation, developed to improve the pharmacokinetics of current
      medium molecular weight HES solutions. This study was designed to explore the
      effects of HES 130/0.4 on pulmonary capillary permeability (PCP), production of
      cytokines, and activation of transcription factor in septic rats induced by cecal
      ligation and puncture (CLP). MATERIALS AND METHODS: Adult male Sprague Dawley
      rats were randomly divided into six groups (six rats/group): saline controls (30
      ml/kg); CLP plus saline (30 ml/kg); CLP plus HES (7.5, 15, or 30 ml/kg,
      respectively), and HES alone (30 ml/kg). Mean arterial blood pressure and heart
      rate were monitored during the experiment process. Myeloperoxidase (MPO)
      activity, wet/dry weight ratio, PCP, tumor necrosis factor alpha (TNF-alpha),
      interleukin (IL)-6, IL-10, and nuclear factor-kappa B (NF-kappaB) were
      investigated at 6 h. RESULTS: We demonstrated that CLP could provoke significant
      injury in lung, characterized by increase in PCP, wet/dry weight ratio, MPO
      activity, TNF-alpha, IL-6, and IL-10 level, and NF-kappaB activation. Without
      obvious influence on systemic macro-hemodynamics, HES 15 ml/kg and 30 ml/kg
      significantly reduced CLP-induced elevation of pulmonary capillary permeability,
      wet/dry weight ratio, and production of IL-6. Meanwhile, HES 15 ml/kg increased
      IL-10 level and HES 7.5, 15, and 30 ml/kg suppressed MPO activity, TNF-alpha
      level, and NF-kappaB activation. CONCLUSION: HES 130/0.4 can inhibit CLP-induced
      PCP by attenuating pulmonary inflammation and NF-kappaB activation in vivo.

PMID- 16616764
TI  - Antiproteolytic action of orally delivered insulin using pH-responsive hydrogels
      in a rat burn model.
AB  - Subcutaneously delivered small doses of insulin has shown beneficial effects on
      burn injury-induced muscle wasting and wound healing. To improve the method of
      insulin treatment for clinical settings, this study investigated the effect of
      insulin delivered orally using pH-responsive poly(methacrylic-g-ethylene glycol)
      (P(MAA-g-EG)) hydrogels in a 20% total burn surface area rat burn injury model.
      P(MAA-g-EG) were synthesized in-house and insulin release characteristics were
      performed in vitro. Young rats weighing 80-150 g were subjected to 15-20% total
      body surface area burn injury and treated with insulin-containing hydrogels
      enclosed in gelatin capsules for 3 days. The dosage was adjusted to match 0.25 U
      (day 1), 0.5U (day 2), and 1.0 U (day 3) per 100 grams of body weight. All
      animals were housed in metabolic cages and their physical activity, body weight,
      food consumption, water uptake, circulating glucose levels, and urinary tyrosine
      content were monitored for 4 to 15 days after burn. Results show that the orally
      delivered insulin restored the body weight of burned rats and influenced wound
      healing, similar to subcutaneous delivery. Measured glucose levels showed
      significantly less perturbation, suggesting the possibility of increasing the
      dosage. In conclusion, muscle wasting can be significantly inhibited by the oral
      administration of insulin using pH-responsive hydrogels.

PMID- 16616765
TI  - Increased brain uptake and brain to blood efflux transport of 14C-GABA in
      spontaneously hypertensive rats.
AB  - The brain uptake and brain to blood efflux transport of (14)C-GABA were studied
      in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats
      using 20 min bilateral in situ brain perfusion in rats anesthetized using
      urethane. The volume of distribution (Vd) of (14)C-GABA into cerebrospinal fluid
      (CSF) and brain regions (cortex, diencephalon, cerebellum, and brain stem) was
      significantly greater in SHR than in the corresponding regions in WKY rats
      (p<0.05). The estimated Vd value of (14)C-GABA in CSF of SHR was 3.4 fold greater
      than that in WKY. Also compared to WKY, the Vd of (14)C-GABA into cerebellum and
      cortex of SHR was 15.3 fold and 19.4 fold greater, respectively. Although the
      study of blood-brain barrier (BBB) integrity using (3)H-mannitol revealed
      increased paracellular permeability at the brain capillaries of SHR when compared
      to WKY rats, this was found to be only partially responsible for the increased
      (14)C-GABA uptake. The study of brain to blood efflux transport of (14)C-GABA
      (after loading of brain with (14)C-GABA by vascular perfusion) revealed that the
      half-time of elimination was significantly shorter in SHR (5.35+/-0.66 min) than
      in WKY rats (14.83+/-1.94 min), (p<0.001). HPLC analysis revealed that GABA
      concentrations in brain extracts and CSF of SHR were similar to those in WKY rats
      (p>0.05). The faster efflux in SHR might be, at least partially, responsible to
      compensate for increased uptake of this neurotransmitter and to preserve the
      protective function of BBB towards GABA. The protective function of the BCSFB
      towards GABA appears to be also preserved, since systemic infusion of GABA within
      a wide range of administered doses (0.004-5.00 mg/kg) produced an increase in
      GABA CSF concentration from around 0.5 microM to only 11 microM, and the obtained
      pattern of CSF GABA concentrations under these conditions did not differ between
      SHR and WKY rats, as revealed by HPLC.

PMID- 16616766
TI  - The positive inotropic effect of the aqueous extract of Convallaria keiskei in
      beating rabbit atria.
AB  - The positive inotropic effect of the aqueous extract of Convallaria keiskei (ACK)
      and the possible mechanisms responsible for this effect were investigated in
      beating rabbit atria. ACK significantly increased atrial stroke volume, pulse
      pressure, and cAMP efflux in beating rabbit atria. The effects were not altered
      by pre-treatment with staurosporine and diltiazem, a non-selective protein kinase
      inhibitor and an L-type Ca2+ channel blocker, respectively. In addition, ACK
      markedly increased the K+ concentration in the beating atria-derived perfusate.
      Convallatoxin, a well-known digitalis-like cardiac glycosidic constituent of ACK,
      also increased atrial stroke volume and pulse pressure but did not alter the cAMP
      efflux level. The increases in atrial stroke volume and pulse pressure induced by
      convallatoxin were not also altered by pre-treatment with diltiazem. These
      results suggest that the ACK-induced positive inotropic effect in beating rabbit
      atria may, at least in part, be due to the digitalis-like activity of
      convallatoxin.

PMID- 16616767
TI  - Opiate withdrawal induces dynamic expressions of AMPA receptors and its
      regulatory molecule CaMKIIalpha in hippocampal synapses.
AB  - Adaptive changes in brain areas following drug withdrawal are believed to
      contribute to drug seeking and relapse. Cocaine withdrawal alters the expression
      of GluR1 and GluR2/3 subunits of alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptors in nucleus accumbens or amygdala, but the
      influence of drug withdrawal on hippocampus is little known. Here, we have
      examined the expression of GluR1 and GluR2/3 in hippocampal membrane and synaptic
      fractions following repeated morphine exposure and subsequent withdrawal.
      Repeated morphine exposure for 12 d increased GluR1 and GluR2/3 in synaptosome
      but not in membrane fraction. Interestingly, CaMKIIalpha, known to be able to
      regulate the function of AMPA receptors, was decreased in synaptosome but not in
      membrane fraction; pCaMKIIalpha, the phosphorylated form of CaMKIIalpha, was
      increased in both fractions. However, during opiate withdrawal, GluR1 was
      generally reduced while GluR2/3 was prominently increased in both fractions;
      pCaMKIIalpha was strongly decreased immediately after withdrawal, but detectably
      increased in late phase of morphine withdrawal in both fractions. Importantly,
      the opiate withdrawal-induced increase in GluR2/3 was dependent on the activation
      of glucocorticoid receptors and NMDA receptors, as it was prevented by the
      glucocorticoid receptor antagonist RU38486, or intrahippocampal injection of the
      NMDA receptor antagonist AP-5 or the antagonist to NR2B-containing NMDA
      receptors, Ro25-6981. These findings indicate that opiate withdrawal induces
      dynamic expression of GluR1 and GluR2/3 subunits of AMPA receptors in hippocampal
      synapses, possibly revealing an adaptive process of the hippocampal functions
      following opiate withdrawal.

PMID- 16616768
TI  - Lysophospholipids elevate [Ca2+]i and trigger exocytosis in bovine chromaffin
      cells.
AB  - Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are responsible for
      many physiological functions, including angiogenesis, neuronal survival, and
      immunity. However, little is known about their effects in modulating the stimulus
      secretion coupling in bovine chromaffin cells. The result of PCR showed that at
      least two receptors (S1P(3) and LPA(1)) were expressed in bovine chromaffin
      cells. The elevation of [Ca(2+)](i) by S1P was fast and sustaining; but the
      elevation by LPA was slow and transient. The EC(50) for S1P and LPA in elevating
      the [Ca(2+)](i) were 0.55+/-0.01 and 0.54+/-0.40microM, respectively. This
      elevation could be totally blocked by thapsigargin, 2-APB, and U73122. Pertussis
      toxin pretreatment inhibited about half of the elevation in [Ca(2+)](i)
      suggesting the involvement of G(i) and other G-proteins. Repetitive [Ca(2+)](i)
      elevations elicited by S1P, but not LPA, were inhibited by ryanodine. S1P was
      more effective than LPA in triggering exocytosis as measured by the changes in
      membrane capacitance. The whole-cell Ca(2+) current was inhibited by both
      lysophospholipids but Na(+) current was inhibited by S1P only. These results
      suggest the differential effects of LPA and S1P in releasing Ca(2+) from the
      intracellular Ca(2+) stores and modulating the stimulus-secretion coupling in
      bovine chromaffin cells.

PMID- 16616769
TI  - The antiallodynic effect of NMDA antagonists in neuropathic pain outlasts the
      duration of the in vivo NMDA antagonism.
AB  - Clinical reports have described a long-lasting relief in neuropathic pain
      patients treated with NMDA receptor antagonists; it is unclear, however, what
      mediates this effect. In this work, we have used two NMDA antagonists of
      different class to investigate if the antiallodynic effects in a rat neuropathy
      model can outlast their in vivo NMDA antagonism. Both the uncompetitive NMDA
      antagonist ketamine and the glycine(B) antagonist MRZ 2/576 inhibited neuronal
      responses to iontophoretic NMDA in anaesthetised rats with the time course
      consistent with their known pharmacokinetics (t(1/2) approximately 10-12min,
      similar in control and nerve-injured rats). Surprisingly, the antiallodynic
      effects of the same doses of the NMDA antagonists in the neuropathic pain model
      were long-lasting (>3h with ketamine, >24h with MRZ 2/576). The effect of
      ketamine was further prolonged (>24h) when combined with a short-acting opioid,
      fentanyl, which only produced a short effect ( approximately 40min) when given
      alone. The duration of centrally mediated side effects of ketamine and MRZ 2/576
      was short, similar to the in vivo NMDA antagonism. We speculate that NMDA
      receptor blockade may down-regulate the central sensitisation triggered by nerve
      injury, resulting in a long-lasting antiallodynic effect. Development of short
      acting NMDA antagonists could represent a strategy for improving their
      tolerability.

PMID- 16616770
TI  - Phosphorous retardation and breakthrough into well water in a soil-aquifer
      treatment (SAT) system used for large-scale wastewater reclamation.
AB  - Retardation and breakthrough of phosphorous in the soil/sediment profiles of a
      SAT system at the Shafdan wastewater treatment plant, Israel, were investigated
      in situ. Area-weighted average effluent load to the whole site was 65 m yr(-1).
      Annual average concentrations of P in the recharged effluent ranged between about
      1.5 and 7.7 mg L(-1) during 25 yr of operation, while P in groundwater remained
      <or= 0.05 mg L(-1) in most wells. Recharge is done through an overlying layer of
      >40 m sandy soil/sediment formations. By combining results of isotherm tests,
      long-term monitoring of phosphorous (P) in solid and liquid phases of the
      recharge site, a simple multi-cell tracer-movement model and measured chloride
      breakthrough curves to the groundwater we calculated P distribution coefficients
      and estimated the retardation factor of P. Laboratory measured, isotherm-based
      distribution coefficient, Kd(I), was about 4-6 L kg(-1) at equilibrium P
      concentration <6 mg L(-1), while field-based Kd(F) was considerably higher,
      reaching about 20-55 L kg(-1) after a load of around 1800 m effluent was
      recharged. Measured P breakthrough times into two shallow observation wells were
      19-21 yr. Calculated P breakthrough times using Kd(F) data agreed with
      observations while those calculated using Kd(I) grossly underestimated
      retardation and predicted much shorter breakthrough times. This validated the
      approach and model used. Estimated P breakthrough times to the deeper observation
      wells and the recovery wells are more than 100 yr and 400-1100 yr, respectively.
      These estimates show that P contamination of the reclaimed effluents in the
      Shafdan plant will not be a problem in the foreseeable future.

PMID- 16616771
TI  - Removal of humic substances (HS) from water by electro-microfiltration (EMF).
AB  - Humic substances (HS) represent the common agents contributing to flux decline
      during membrane filtration of natural water. In order to minimize the fouling
      during microfiltration (MF) of HS, modifying the operation of MF presents a
      promising alternative. A laboratory-scale electro-microfiltration (EMF) module
      was used to separate Aldrich HS from water by applying a voltage across the
      membrane. The presence of an electric field significantly reduced the flux
      decline. A flux comparable to that of ion-free water was attained when the
      voltage was near the critical electric field strength (Ecritical), i.e., the
      electrical field gradient that balances the advective and electrophoretic
      velocities of solute. At an applied voltage of 100 V (approximately 110 V/cm), it
      was able to reduce UV absorbance at 254 nm (UV254), total organic carbon (TOC)
      and trihalomethane formation potential (THMFP) by over 50% in the permeate.
      Results from 1H nuclear magnetic resonance (1H NMR) analysis suggest that the
      aromatic and functionalized aliphatic fractions decreased significantly in the
      permeate. The charged HS have large molecule weight compared with those passing
      through membrane. Results clearly indicate that a combination of electric force
      with MF can increase HS rejection and decrease flux decline. Electrophoretic
      attraction was the major mechanism for the improvement of flux and rejection over
      time.

PMID- 16616772
TI  - Restriction of amino acids extends lifespan in Drosophila melanogaster.
AB  - Dietary restriction extends adult Drosophila melanogaster life span when the
      concentration of dietary yeast is diluted in a media with abundant carbohydrates.
      Here we vary the concentration of casein as a source of amino acids in adult diet
      to uncover a quality of nutrient yeast responsible for longevity control.
      Longevity is maximized upon diet with intermediary levels of casein. Differences
      in survival are not caused by elevated age-independent mortality; the longevity
      maximum at intermediate casein does not arise because casein is non-specifically
      harmful at higher concentrations. Furthermore, fecundity increases when the level
      of dietary casein is elevated. The demographic phenotypes of adult Drosophila
      maintained on intermediate levels of casein resemble their response to limited
      dietary yeast. Dietary restriction through dilution of yeast may extend longevity
      because this limits the intake of amino acids.

PMID- 16616773
TI  - Review on fluoride-releasing restorative materials--fluoride release and uptake
      characteristics, antibacterial activity and influence on caries formation.
AB  - OBJECTIVES: The purpose of this article was to review the fluoride release and
      recharge capabilities, and antibacterial properties, of fluoride-releasing dental
      restoratives, and discuss the current status concerning the prevention or
      inhibition of caries development and progression. METHODS: Information from
      original scientific full papers or reviews listed in PubMed (search term:
      fluoride release AND (restorative OR glass-ionomer OR compomer OR polyacid
      modified composite resin OR composite OR amalgam)), published from 1980 to 2004,
      was included in the review. Papers dealing with endodontic or orthodontic topics
      were not taken into consideration. Clinical studies concerning secondary caries
      development were only included when performed in split-mouth design with an
      observation period of at least three years. RESULTS: Fluoride-containing dental
      materials show clear differences in the fluoride release and uptake
      characteristics. Short- and long-term fluoride releases from restoratives are
      related to their matrices, setting mechanisms and fluoride content and depend on
      several environmental conditions. Fluoride-releasing materials may act as a
      fluoride reservoir and may increase the fluoride level in saliva, plaque and
      dental hard tissues. However, clinical studies exhibited conflicting data as to
      whether or not these materials significantly prevent or inhibit secondary caries
      and affect the growth of caries-associated bacteria compared to non-fluoridated
      restoratives. SIGNIFICANCE: Fluoride release and uptake characteristics depend on
      the matrices, fillers and fluoride content as well as on the setting mechanisms
      and environmental conditions of the restoratives. Fluoride-releasing materials,
      predominantly glass-ionomers and compomers, did show cariostatic properties and
      may affect bacterial metabolism under simulated cariogenic conditions in vitro.
      However, it is not proven by prospective clinical studies whether the incidence
      of secondary caries can be significantly reduced by the fluoride release of
      restorative materials.

PMID- 16616774
TI  - Real time spectral analysis during phytochrome chromophore and chromoprotein
      purification.
AB  - The plant photoreceptor phytochrome senses light quality and quantity in the red
      region of the spectrum, directing adaptation and development. The functional holo
      protein is a dimeric chromoprotein which is formed by an autoassembly reaction
      between the translation product and the open chain tetrapyrroles phytochromobilin
      (PPhiB) or phycocyanobilin (PCB). We are interested in structure/function
      relationships within the phytochrome molecule, in particular chromophore/protein
      interaction during the assembly and photoactivation, using IR and NMR
      spectroscopy. For this we use an automated F/HPLC system running in a darkroom to
      purify large amounts of protein and chromophore separately. To obtain highly pure
      PCB chromophore we developed improved extraction and purification methods in
      which the final step is RPC-18 HPLC. As there are many spectrally only slightly
      different tetrapyrroles in the extract, the triple-wavelength monitoring offered
      by the F/HPLC detector was inadequate for distinguishing between PCB and
      impurities. Furthermore, lambda(max) for the phytochrome Pfr signalling state
      lies between 705 and 730 nm, beyond the range of the detector. Also, as both holo
      protein and chromophore are photoactive, we wished to minimize light exposure of
      the eluate. We therefore implemented a miniature CCD-based flow UV-vis
      spectrophotometer using a xenon flash and quartz fiber optics enabling us monitor
      the entire 250-800 nm spectrum of the eluate to an accuracy of +/-3 x 10(-3)A in
      real time. The instrumentation described can be added to any chromatographic
      system, thereby allowing the purification of any molecule to be monitored easily
      and efficiently.

PMID- 16616775
TI  - Screening for soluble expression constructs using cell-free protein synthesis.
AB  - The SH2 domain of STAT6 was chosen to test the in vitro protein synthesis as a
      screening tool. Goal of the screening was to obtain constructs which produce
      soluble protein in E. coli. The expression of 70 different constructs using an E.
      coli based cell-free system revealed two constructs, which give partly soluble
      protein. The introduction of two mutations, which had been suggested by a
      structural based alignment of 20 different SH2 domains lead to increased
      solubility. The expression of both constructs in E. coli followed by an affinity
      and size exclusion chromatography resulted in milligram quantities of highly
      purified protein.

PMID- 16616776
TI  - Directed growth and selective differentiation of neural progenitor cells on
      micropatterned polymer substrates.
AB  - Directional growth and differentiation of adult rat hippocampal progenitor cells
      (AHPCs) were investigated on micropatterned polymer substrates in vitro.
      Astrocytes or AHPCs cultured on micropatterned polystyrene substrates chemically
      modified with laminin exhibited over 75% alignment in the groove direction. AHPCs
      co-cultured with astrocytes preferentially acquired neuronal morphology, with
      nearly double the percentage of cells expressing class III beta-tubulin on the
      micropatterned half of the substrate, as opposed to the planar half of the
      substrate, or compared to those growing in the absence of astrocytes. This
      indicates that substrate three-dimensional topography, in synergy with chemical
      (laminin) and biological (astrocytes) guidance cues, facilitates neuronal
      differentiation of the AHPCs. Through multi-dimensional cell-cell interactions,
      this environment provides spatial control selectively enhancing neuronal
      differentiation and neurite alignment on topographically different regions of the
      same substrate. Integrating these cues is important in understanding and
      controlling neural stem cell differentiation and designing scaffolds for guided
      nerve regeneration.

PMID- 16616777
TI  - Guidance of liver and kidney organotypic cultures inside rectangular silicone
      microchannels.
AB  - We have studied the effect of rectangular polydimethylsiloxane (PDMS)
      microchannels on the behavior of embryonic liver and kidney explants maintained
      in contact with these microchannels. The microchannel widths were varied from 35
      to 300 microm and depth from 45 to 135 microm. The growth of these tissue types
      were compared to the development on flat silicone and plastic control material.
      At seeding, due to the viscoelastic properties of both organs, "capillary-like
      filling" was observed inside the narrowest microchannels. In those cases, the
      tissues grew to a confluent layer joining the microchannels with no cell
      migration and proliferation inside the microchannels. In the largest
      microchannels, only a weak migration was observed and the cellular behavior
      appears quite similar to that of PDMS flat culture conditions. In intermediate
      geometries, we observed different tissue growth progressed inside those
      microchannels with an average growth properties inside the microchannels when
      compared to other sizes. The liver tissues velocity of up to 72 microm/day
      resulting to form a dense three-dimensional multicellular 'liver-like tissue'.
      Scanning electron microscopy (SEM) observations demonstrated that the tissue was
      organized like an epithelial layer with round cells embedded in an extracellular
      matrix. Liver cell mobility may result primarily from the activity of the
      marginal cells, whereas the sub-marginal cells appeared passively dragged.
      Parenchymal organization demonstrating differentiated states was also observed.
      Kidney grew mainly on the microchannel walls and the tissues never appeared dense
      and organized as the liver ones.

PMID- 16616778
TI  - Molecular response of leukemia HL-60 cells to genistein treatment, a proteomics
      study.
AB  - Genistein (GEN) is a natural protein tyrosine kinase inhibitor. We analyzed the
      molecular response of HL-60 cells to GEN treatment by gel-based proteomics
      approach. Fourteen differentially expressed proteins which are functionally
      involved in metabolism, cell signaling, RNA processing, cell proliferation and
      motility, and chaperones were identified. Both the dose- and time-dependent up
      regulation of Hsp70 protein 8 and heterogeneous nuclear ribonucleoprotein (hnRNP)
      H1, and the down-regulation of Rab14, hnRNP C and stathmin-1 by GEN were verified
      by immunoblot analysis. Our novel findings provide insightful clues to the
      potential therapeutic targets for leukemia treatment in diverse tyrosine kinase
      dependent cellular pathways.

PMID- 16616779
TI  - Reasonable suspicion: a pilot study of pediatric residents.
AB  - OBJECTIVES: To identify pediatric residents' understanding and interpretation of
      reasonable suspicion, in the context of mandated reporting of suspected child
      abuse. METHOD: A survey was administered to pediatrics and combined
      medicine/pediatrics residents. An open-ended question plus three operational
      frameworks for interpreting likelihood examined how residents conceived of
      reasonable suspicion. Responses were examined for evidence of a group standard,
      and also compared for internal consistency. RESULTS: Forty-two of 49 residents
      completed the survey (86% response rate). There were no significant differences
      in responses based on age, gender, year of residency, or anticipated practice
      type. Respondents exhibited wide variation in the thresholds they set for
      reasonable suspicion. On a Differential Diagnosis scale, 10% indicated that
      "abuse" would have to rank 1st or 2nd; 45% set the threshold at 3rd or 4th; while
      45% stated that abuse could be as low as 5th to 10th and still qualify as
      reasonable suspicion. Using a Estimated Probability scale, 9.5% indicated that
      "abuse" would need to be >75% likely before reasonable suspicion existed; 28.5%
      stated that a 60-70% likelihood was needed; 38% identified the necessary
      likelihood as 40-50%; and 24% set the threshold as low as 10-35%. In comparing
      individual resident responses for the two scales, 83.3% were internally
      inconsistent. CONCLUSION: There was no consensus among pediatric residents with
      regard to (1) a standard meaning for reasonable suspicion, (2) a standard
      application of reasonable suspicion, or (3) how likely "abuse" must be before
      reasonable suspicion can be said to exist. Additionally, many residents'
      conceptions of reasonable suspicion were internally inconsistent.

PMID- 16616780
TI  - Antiapoptotic and immunomodulatory effects of chlorophyllin.
AB  - Chlorophyllin (CHL) was earlier shown to reduce the level of intracellular ROS
      and apoptosis induced by ionizing radiation and 2,2'-azobis(2
      propionimidinedihydrochloride) (AAPH). In the present studies, the effect of CHL
      on radiation-induced immunosuppression and modulation of immune responses in mice
      was examined. Chlorophyllin inhibited the in vitro lymphocyte proliferation
      induced by concanavalin A (Con A) in a dose dependent manner at doses>or=50
      microM. At lower doses (10 microM) CHL significantly inhibited activation induced
      cell death (AICD) in Con A stimulated spleen cells. Spleen cells obtained from
      CHL treated mice showed an inhibition of response to Con A depending on dose of
      CHL and the time after its administration. Spleen cells obtained from CHL treated
      mice (24 h) showed lower inhibition of response to Con A following in vitro (5
      Gy) as well as whole body irradiation (2 Gy). The expression of antiapoptotic
      genes bcl-2 and bcl-xL was up-regulated in these cells. Chlorophyllin treatment
      of mice led to splenomegaly and increase in the number of peritoneal exudate
      cells (PEC). The numbers of T cells, B cells and macrophages in the spleen were
      also increased. Increased phagocytic activity was seen in PEC obtained from CHL
      treated mice. Most importantly, CHL administration to mice immunized with sheep
      red blood cells (SRBC) augmented both humoral and cell-mediated immune responses.

PMID- 16616781
TI  - Mapping and molecular characterization of novel monoclonal antibodies to
      conformational epitopes on NH2 and COOH termini of mammalian tryptophanyl-tRNA
      synthetase reveal link of the epitopes to aggregation and Alzheimer's disease.
AB  - Tryptophanyl-tRNA synthetase (TrpRS) is an interferon-induced phosphoprotein with
      autoantigenic and cytokine activities detected in addition to its canonical
      function in tRNA aminoacylation. The availability of monoclonal antibodies (mAbs)
      specific for TrpRS is important for development of tools for TrpRS monitoring. A
      molecular characterization of two mAbs raised in mice, using purified,
      enzymatically active bovine TrpRS as the inoculating antigen, is presented in
      this report. These IgG1 antibodies are specific for bovine, human and rabbit but
      not E. coli TrpRS. Immunoreactivity and specificity of mAbs were verified with
      purified recombinant hTrpRS expressed in E. coli and TrpRS-derived synthetic
      peptides. One of the mAbs, 9D7 is able to disaggregate fibrils formed by Ser32
      Tyr50 TrpRS-peptide. Epitope mapping revealed that disaggregation ability
      correlates with binding of 9D7 to this peptide in ELISA and immunocytochemistry.
      This epitope covers a significant part of N-terminal extension that suggested to
      be proteolytically deleted in vivo from the full-length TrpRS whereas remaining
      COOH-fragment possesses a cytokine activity. For epitope mapping of mAb 6C10, the
      affinity selected phage-displayed peptides were used as a database for prediction
      of conformational discontinuous epitopes within hTrpRS crystal structure. Using
      computer algorithm, this epitope is attributed to COOH-terminal residues Asp409
      Met425. In immunoblotting, the 6C10 mAb reacts preferably with (i) oligomer than
      monomer, and (ii) bound than free TrpRS forms. The hTrpRS expression was shown to
      correlate with growth rates of neuroblastoma and pancreatic cancer cells.
      Immunohistochemically both mAbs revealed extracellular plaque-like aggregates in
      hippocampus of Alzheimer's disease brain.

PMID- 16616782
TI  - Identification of CD36 as a new surface marker of marginal zone B cells by
      transcriptomic analysis.
AB  - Follicular (FO) B cells and marginal zone (MZ) B cells belong to the mature B
      cell population in spleen of mice. To identify new surface markers of these
      mature B cell subsets, we compared gene expression profiles of FO and MZ B cells
      by DNA microarray using FACS-sorted mouse FO and MZ B cells. From 14,000 mouse
      genes, 27 membrane proteins were expressed mainly in MZ B cells while another 22
      membrane proteins expressed largely in FO B cells. Using FACS analysis, we
      identified that CD36, CD68, and CD49e were expressed on MZ B cells but not on FO
      B cells. In addition, using semi-quantitative PCR, we found that the mRNA of
      CD131 were much more abundant in MZ B cells. These results revealed new
      phenotypic properties of MZ and FO B cells, and would facilitate further studies
      in the differentiation and functions of these mature B cells.

PMID- 16616783
TI  - Clinical significance and epidemiology of non-pigmented rapidly growing
      mycobacteria in a university hospital.
AB  - OBJECTIVES: To study the clinical significance and epidemiology of Non-pigmented
      rapidly growing mycobacteria (NPRGM) during a 13-year period. METHODS: We
      performed a retrospective study of patients with isolates of NPRGM to evaluate
      their clinical significance. We also analyzed the strains using Randomly
      Amplified Polymorphic DNA (RAPD) analysis to evaluate the relationship between
      strains. RESULTS: Between 1990 and 2003, 65 patients had an isolate of NPRGM.
      Twenty of them were considered significant (19 cases) or doubtful (1 case). Many
      cases were skin and soft tissue infections. Six cases were foreign-body related.
      All the patients recovered with antibiotic therapy and removal of the foreign
      body. All the patients were apparently unrelated, despite 56.9% of the isolates
      were detected between 1995 and 1997. RAPD analysis was performed on 43 strains,
      and showed only a cluster of two Mycobacterium chelonae isolates. Both of them
      were related with contamination of a laboratory reactive, and were considered non
      significant. CONCLUSION: In our hospital, almost one-third of the isolates of
      NPRGM were significant, being this percentage higher for skin and soft tissue
      isolates. Patients were cured with antibiotic therapy, but the removal of foreign
      bodies appeared to be necessary for a good outcome. A minor pseudo-outbreak was
      detected. No predominant strain was detected.

PMID- 16616784
TI  - Novel isoforms of NADPH-oxidase in cerebral vascular control.
AB  - Reactive oxygen species (ROS) are thought to play an important role in the
      initiation and progression of a variety of vascular diseases. Furthermore,
      accumulating evidence indicates that ROS may also serve as important cell
      signalling molecules for the regulation of normal vascular function. Recently, a
      novel family of proteins (Nox1, 2 and 4) that act as the catalytic subunit of the
      superoxide (O2-) producing enzyme NADPH-oxidase has been discovered in vascular
      cells. There is now preliminary evidence suggesting that NADPH-oxidase-derived
      ROS may serve as a physiological vasodilator mechanism in the cerebral
      circulation. Moreover, the activity of NADPH-oxidase is profoundly greater in
      cerebral versus systemic arteries. Studies have shown that Nox1, Nox2 (also known
      as gp91phox) and Nox4 are all expressed in cerebral arteries, suggesting that
      multiple isoforms of NADPH-oxidase may be important for ROS production by
      cerebral arteries. Enhanced NADPH-oxidase activity is associated with several
      vascular-related diseases, including hypertension, stroke, subarachnoid
      haemorrhage and Alzheimer's dementia; however, the consequences of this for
      cerebral vascular function are controversial. For example, there is some evidence
      suggesting that NADPH-oxidase-derived O2- may play a role in endothelial
      dysfunction of cerebral arteries and a subsequent rise in cerebral vascular tone,
      associated with hypertension. However, activation of NADPH-oxidase elicits
      cerebral vasodilatation in vivo, and this mechanism is enhanced in chronic
      hypertension. While further supportive evidence is needed, it is an intriguing
      possibility that NADPH-oxidase-derived ROS may play a protective role in
      regulating cerebral vascular tone during disease.

PMID- 16616785
TI  - Two-dimensional analysis of proteinase activity.
AB  - A method was developed to separate proteinases in a complex mixture in two
      dimensions followed by activity detection using class specific substrates. Using
      this method, serine proteinase activity was evaluated in gut extracts from a
      stored-product pest, Plodia interpunctella. With the substrate n-alpha-benzoyl-l
      arginine rho-nitroanilide, three major groups of at least six trypsin-like
      activities were identified, consisting of proteinases with estimated molecular
      masses of 25-27, 40-41, and 289 kDa, and all with an acidic pI of 4.7-5.5. With
      the substrate, n-succinyl-ala-ala-pro-phenylalanine rho-nitroanilide, two groups
      of at least five chymotrypsin-like activities were detected, with estimated
      molecular masses of 28 and 192 kDa and pI values ranging from 6.1 to 7.3. Using
      the 2-DE activity blot method, information was obtained on the relative number
      and physical properties of serine proteinases in a mixture of insect gut
      proteinases without prior fractionation.

PMID- 16616786
TI  - The effects of early post-hatching changes of imprinting object on the pattern of
      monocular/unihemispheric sleep of domestic chicks.
AB  - The pattern of monocular/unihemispheric sleep (Mo-Un sleep) was studied
      behaviourally in male and female chicks after early post-hatching changes of the
      imprinting object. Chicks were reared with an imprinting object on day 1 post
      hatching which was removed or changed on day 2. On day 1, time spent in binocular
      sleep (both eyes closed) was similar in male and female chicks, though the number
      of episodes was lower in females than in males. There was no eye-closure bias in
      the pattern of Mo-Un sleep (one eye shut and the other open) in chicks of both
      sexes. On day 2, chicks subjected to the removal of imprinting object showed less
      time and number of episodes of binocular sleep than control chicks and chicks
      subjected to changes of imprinting object. There was no eye-closure bias in
      control chicks whilst a significant bias for more right Mo-Un sleep was recorded
      in chicks after removal and changes of imprinting object of both sexes. It is
      suggested that the removal or changes of imprinting object would cause a decrease
      of binocular sleep and trigger processes associated to secondary imprinting
      involving the left hemisphere. The bias for more right Mo-Un sleep (right eye
      closure) could be the by-product of consolidation processes of secondary
      imprinting memories in the left hemisphere and/or of more left eye-opening as a
      result of periodical awakening of right hemisphere to control the environment
      after a stressful condition such as the removal or change of imprinting object.

PMID- 16616787
TI  - Attentional performance of C57BL/6 and DBA/2 mice in the 5-choice serial reaction
      time task.
AB  - C57BL/6 and DBA/2 were compared in the 5-choice serial reaction time task for
      differences in performance related to attention and impulsivity. The goal was to
      examine behavioural processes in mice that may relate to ADHD in humans. Groups
      of male mice were trained to nose-poke in response to a stimulus light presented
      randomly in one of five holes; correct responses were reinforced with food.
      During training the stimulus duration (SD) was reduced progressively from 60 to
      0.5s. The C57BL/6 and DBA/2 mice did not differ during early stages of training
      when attentional demands were low (SD of 60, 10 or 5s). As task demands
      increased, strain differences emerged; C57BL/6 mice were more accurate than DBA/2
      mice with stimuli of 2, 1 and 0.5s. DBA/2 mice also made more anticipatory
      (impulsive) responses during inter-trial intervals than C57BL/6 mice at SD of 5,
      2, 1 and 0.5s. The ability to carry out the task was present in both strains of
      mice but they differed significantly in the levels of performance that were
      achieved. It is argued that the differences in accuracy and anticipatory
      responding were closely related and that the primary difference between the
      strains may be in impulsivity.

PMID- 16616788
TI  - Effects of cadmium on aneuploidy and hemocyte parameters in the Pacific oyster,
      Crassostrea gigas.
AB  - Pacific oysters, Crassostrea gigas, are commonly reared in estuaries where they
      are exposed to anthropogenic pollution. Much research has been made on the
      toxicity of cadmium to aquatic organisms because the compound recurrently
      contaminates their environment. Our study examined the influence of cadmium on
      aneuploidy level (lowered chromosome number in a percentage of somatic cells) and
      hemocyte parameters in C. gigas at different stages of life. Adults and juveniles
      were exposed to two different concentrations of cadmium. The first concentration
      applied was equivalent to a peak value found in Marennes-Oleron bay (Charente
      Maritime, France; 50 ngL(-1)) and the second was 10 times higher (500 ngL(-1)).
      Exposure to 50 ngL(-1) cadmium caused a significant decrease in the survival time
      of C. gigas, but exposure to 500 ngL(-1) surprisingly affected the survival time
      positively. Significant differences in aneuploidy level were observed between the
      cadmium treatments and the control in adults but not in juveniles or the
      offspring of the adult groups. The effects of cadmium on hemocyte parameters were
      analyzed by flow cytometry. Several hemocyte parameters increased significantly
      after 21 days of cadmium exposure and subsequently decreased. Phenoloxidase-like
      activity, evaluated by spectrophotometry, varied over the time of the experiment
      and increased after 66 days of contact with 500 ngL(-1) cadmium. Taken together,
      cadmium at environmentally relevant concentrations seems to have only moderate
      effects on aneuploidy and hemocyte parameters.

PMID- 16616789
TI  - Induction of micronuclei and other nuclear abnormalities in mussels exposed to
      bisphenol A, diallyl phthalate and tetrabromodiphenyl ether-47.
AB  - Analysis of micronuclei, nuclear buds, bi-polynucleated and fragmented-apoptotic
      cells was performed in gills of blue mussels exposed for 3 weeks to sublethal
      concentrations of bisphenol A, diallyl phthalate (for the both nominal
      concentration 50 ppb) and to tetrabromodiphenyl ether-47 (nominal concentration 5
      ppb). Fourteen specimens from each treatment and control group were used for the
      analysis. Our results demonstrated a significant increase in micronuclei
      frequency after the treatment with bisphenol A (P=0.0243), diallyl phthalate
      (P=0.0005) and tetrabromodiphenyl ether-47 (P<0.0001; Mann-Whitney U-test).
      Induction of bi-nucleated (P=0.0028), fragmented-apoptotic (P=0.0004) cells and
      nuclear buds (P=0.0101) was found in mussels exposed to tetrabromodiphenyl ether
      47 while treatment with diallyl phthalate increased the level of fragmented
      apoptotic cells (P=0.0283). Bisphenol A was the only agent that resulted only in
      induction of micronuclei but not any other kind of nuclear injuries.

PMID- 16616790
TI  - Shunting versus inactivation: simulation of GABAergic inhibition in spider
      mechanoreceptors suggests that either is sufficient.
AB  - Afferent neurons entering the central nervous systems of vertebrates and
      invertebrates receive presynaptic inhibition on their axon terminals. This
      usually involves an increase in membrane conductance (shunting) and
      depolarization (primary afferent depolarization, PAD). In arachnids and
      crustaceans the peripherally located parts of afferent neurons also receive
      efferent synapses. GABA (gamma-aminobutyric acid) plays a major role in both
      central and peripheral inhibition, activating chloride channels that depolarize
      the membrane and increase its conductance. Although both central and peripheral
      inhibition have been widely investigated, debate continues about the mechanisms
      involved, especially concerning the relative contributions of shunting versus
      inactivation of sodium channels by depolarization. Sensory neurons innervating
      spider VS-3 slit sensilla are accessible to intracellular recordings during
      mechanical or electrical stimulation. These neurons are inhibited by GABA, and
      both the electrophysiology and pharmacology of this inhibition have been studied
      previously. Here, we developed a Hodgkin-Huxley style model to simulate VS-3
      neuron activity before and after GABA treatment. The model indicates that GABA
      activated chloride current can entirely account for action potential suppression,
      and that either shunting or inactivation are sufficient to produce inhibition.
      This model also demonstrates that slowing of sodium current contributes to
      inhibition.

PMID- 16616791
TI  - Inhibitory effect of total flavone of Abelmoschus manihot L. Medic on NMDA
      receptor-mediated current in cultured rat hippocampal neurons.
AB  - The modulatory effect of Total Flavone of Abelmoschus manihot L. Medic (TFA) on
      NMDA-activated current (I(NMDA)) was investigated in cultured rat hippocampal
      neurons using the whole-cell patch-clamp technique. TFA rapidly and reversibly
      inhibited the I(NMDA) in a concentration-dependent manner. Furthermore, TFA non
      competitively inhibited the I(NMDA) by enhancement of the NMDA receptor
      desensitization. In addition, intracellular application of TFA did not alter the
      TFA inhibition of I(NMDA). These results suggest that the inhibition of the NMDA
      receptor response by TFA could be one of the mechanisms for TFA-mediated
      neuroprotective actions.

PMID- 16616793
TI  - [Ecologic evaluation in the cognitive assessment of brain injury patients:
      generation and execution of script].
AB  - OBJECTIVE: Assessment of executive functions in an everyday life activity,
      evaluating brain injury subjects with script generation and execution tasks.
      MATERIALS AND METHODS: We compared a script generation task to a script execution
      task, whereby subjects had to make a cooked dish. Two grids were used for the
      quotation, qualitative and quantitative, as well as the calculation of an
      anosognosis score. We checked whether the execution task was more sensitive to a
      dysexecutive disorder than the script generation task and compared the scores
      obtained in this evaluation with those from classical frontal tests. Twelve
      subjects with brain injury 6 years+/-4.79 ago and 12 healthy control subjects
      were tested. The subjects carried out a script generation task whereby they had
      to explain the necessary stages to make a chocolate cake. They also had to do a
      script execution task corresponding to the cake making. RESULTS: The 2 quotation
      grids were operational and complementary. The quantitative grid is more sensitive
      to a dysexecutive disorder. The brain injury subjects made more errors in the
      execution task. CONCLUSION: It is important to evaluate the executive functions
      of subjects with brain injury in everyday life tasks, not just in psychometric or
      script-generation tests. Indeed the ecological realization of a very simple task
      can reveal executive function difficulties such as the planning or the sequencing
      of actions, which are under-evaluated in laboratory tests.

PMID- 16616792
TI  - Inhibition of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)
      infectivity by peptides analogous to the viral spike protein.
AB  - Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is the cause
      of an atypical pneumonia that affected Asia, North America and Europe in 2002
      2003. The viral spike (S) glycoprotein is responsible for mediating receptor
      binding and membrane fusion. Recent studies have proposed that the carboxyl
      terminal portion (S2 subunit) of the S protein is a class I viral fusion protein.
      The Wimley and White interfacial hydrophobicity scale was used to identify
      regions within the CoV S2 subunit that may preferentially associate with lipid
      membranes with the premise that peptides analogous to these regions may function
      as inhibitors of viral infectivity. Five regions of high interfacial
      hydrophobicity spanning the length of the S2 subunit of SARS-CoV and murine
      hepatitis virus (MHV) were identified. Peptides analogous to regions of the N
      terminus or the pre-transmembrane domain of the S2 subunit inhibited SARS-CoV
      plaque formation by 40-70% at concentrations of 15-30 microM. Interestingly,
      peptides analogous to the SARS-CoV or MHV loop region inhibited viral plaque
      formation by >80% at similar concentrations. The observed effects were dose
      dependent (IC50 values of 2-4 microM) and not a result of peptide-mediated cell
      cytotoxicity. The antiviral activity of the CoV peptides tested provides an
      attractive basis for the development of new fusion peptide inhibitors
      corresponding to regions outside the fusion protein heptad repeat regions.

PMID- 16616794
TI  - Actual usage and clinical effectiveness of insulin preparations in patients with
      Type 1 diabetes mellitus in Japan: CoDiC-based analysis of clinical data obtained
      at multiple institutions (JDDM 3).
AB  - To clarify the actual usage of insulin preparations and their effectiveness on
      glycaemic control in patients with Type 1 diabetes mellitus in Japan, we analyzed
      clinical data collected via CoDiC, an electronic system for diabetes data
      collection and management, at 28 institutes. Of 18,470 diabetic patients
      registered with CoDiC in June, 2003, 12,279 patients were being treated with
      insulin preparations and/or oral hypoglycemic agents, with 861 of these patients
      having Type 1 diabetes mellitus and 11,418 patients having Type 2 diabetes. Three
      analytical surveys were carried out with the Type 1 diabetes patients. Study I:
      Cross-sectional survey on the treatment in 2002. Six hundred and thirteen
      patients received intensive conventional insulin treatment (ICT). The number of
      patients receiving rapid-acting insulin analogue (RA) was greater than that of
      patients receiving regular insulin (R). Serum CPR was lower in the patients with
      ICT than in the patients with conventional insulin treatment (CT). Study II:
      Survey on the changes in the actual usage and clinical effectiveness of insulin
      preparations, based on the data input in 2001 and 2002. The number of patients
      with ICT using RA insulin markedly increased. Study III: Analysis of the
      participants' clinical course over the 18-month period of the study from the time
      of first consultation. The dose of insulin increased during the term. The average
      HbA1c level fell drastically and reached to 7.5% over the first 9 months of the
      study and then remained between a range of 7.5% and 8% for the rest of the study
      period. In conclusion, ICT is actively performed and the RA insulin analogues are
      widely used in Type 1 diabetic patients in Japan. Basal-bolus therapy should be
      used to treat Type 1 diabetic patients with postprandial serum CPR of less than
      0.5 ng/ml. It is difficult to obtain the ideal glycaemic control in Type 1
      diabetic patients with the currently available insulin preparations.

PMID- 16616795
TI  - Effect of a diet and exercise intervention on oxidative stress, inflammation and
      monocyte adhesion in diabetic men.
AB  - Diabetes increases the risk of coronary artery disease. We examined the effects
      of lifestyle modification on key contributing factors to atherogenesis, including
      oxidative stress, inflammation and cell adhesion. Diabetic men (N=13) were placed
      on a high-fiber, low-fat diet in a 3-week residential program where food was
      provided ad libitum and daily aerobic exercise was performed. In each subject,
      pre- and post-intervention fasting blood was drawn for circulating levels of
      serum lipids, glucose and insulin, oxidative stress marker 8-isoprostaglandin
      F2alpha (8-iso-PGF2alpha), the inflammatory protein C-reactive protein (CRP), and
      soluble intracellular adhesion molecule (sICAM)-1 and sE-selectin as indicators
      of endothelial activation. Using subject sera and human aortic endothelial cell
      (HAEC) culture systems, serum-induced monocyte adhesion, ICAM-1, vascular cell
      adhesion molecule-1 (VCAM-1) and cell surface abundance, and monocyte chemotactic
      protein-1 (MCP-1) production were determined. Nitric oxide (NO), superoxide, and
      hydrogen peroxide production were measured in vitro by fluorometric detection.
      After 3 weeks, significant reductions (p<0.05) in BMI, all serum lipids including
      total cholesterol (pre: 188.9+/-10.1 mg/dL versus post: 146.3+/-3.8 mg/dL) and
      low-density lipoprotein (103.1+/-10.2 mg/dL versus 76.4+/-4.3 mg/dL), fasting
      serum glucose (157.5+/-10.1 mg/dL versus 126.7+/-8.7 mg/dL), insulin (33.8+/-4.0
      microU/ml versus 23.8+/-3.4 microU/ml), homeostasis model assessment for insulin
      resistance, 8-iso-PGF2alpha, CRP, sICAM-1, and sE-selectin were noted. In vitro,
      serum-stimulated monocyte adhesion, cellular ICAM-1 and VCAM-1 expression
      (p<0.05), and fluorometric detection of superoxide and hydrogen peroxide
      production decreased, while a concomitant increase in NO production was noted
      (all p<0.01). A combination of diet and exercise ameliorates oxidative stress,
      inflammation, and monocyte-endothelial interaction. Intensive lifestyle
      modification may improve novel CAD risk factors in men with diabetes.

PMID- 16616796
TI  - Mean frequency derived via Hilbert-Huang transform with application to fatigue
      EMG signal analysis.
AB  - The mean frequency (MNF) of surface electromyography (EMG) signal is an important
      index of local muscle fatigue. The purpose of this study is to improve the mean
      frequency (MNF) estimation. Three methods to estimate the MNF of non-stationary
      EMG are compared. A novel approach based on Hilbert-Huang transform (HHT), which
      comprises the empirical mode decomposition (EMD) and Hilbert transform, is
      proposed to estimate the mean frequency of non-stationary signal. The performance
      of this method is compared with the two existing methods, i.e. autoregressive
      (AR) spectrum estimation and wavelet transform method. It is observed that our
      method shows low variability in terms of robustness to the length of the analysis
      window. The time-varying characteristic of the proposed approach also enables us
      to accommodate other non-stationary biomedical data analysis.

PMID- 16616797
TI  - Oral treatment options for degenerative joint disease--presence and future.
AB  - Alleviation of pain and inhibition of inflammation are the primary goals of
      pharmacotherapy of osteoarthritis (OA). These therapeutic goals can almost always
      be accomplished by the use of analgesics and nonsteroidal anti-inflammatory drugs
      (NSAID). One of the main problems of NSAIDs is their gastrointestinal toxicity,
      for which a prophylactic medication should be considered particularly amongst
      risk groups. Recent studies have shown that COX-2-selective and maybe also non
      selective NSAIDs increase the cardiovascular risk so that their application is
      getting now drastically restricted. Pharmacological results published until now
      suggest that a clinically relevant minor analgesic and/or anti-inflammatory
      effect can be attained with the use of some of the SYmptomatic Slow Acting Drugs
      in OA (SYSADOAs). However, no clinical studies exist, which can positively
      confirm prevention, slowing down or reversal of any advanced joint cartilage
      destruction by any individual medication. Disease modifying therapy is still in
      its infancy; discovery and development of novel therapeutic targets and agents
      are an extremely difficult task, currently challenging many pharmaceutical
      companies and academic institutions.

PMID- 16616798
TI  - Hedgehog signaling in small-cell lung cancer: frequent in vivo but a rare event
      in vitro.
AB  - The hedgehog (HH) signaling pathway plays multiple roles during embryonic
      development and increasing evidence suggests that this embryonic pathway is
      involved in development and progression of several human cancers including those
      of the brain, skin, lung and gastrointestinal tract. To investigate HH signaling
      activity in small-cell lung cancer (SCLC), we have performed gene expression
      analysis on members of the HH pathway on a panel of 20 SCLC cell lines. Sonic
      hedgehog (SHH) expression was detected in only DMS79 and GLC16 and only DMS114
      expressed detectable protein levels of GLI1, one of the key transcription factors
      of the pathway. Involvement of HH signaling in SCLC proliferation was
      investigated in a subset of cell lines using the HH signaling inhibitor
      cyclopamine or small interfering RNA (siRNA) against GLI1. Cells expressing GLI1
      responded only weakly to both cyclopamine and RNA interference, suggesting that
      HH signaling plays only a minor role in the growth of SCLC cell lines. To
      investigate HH pathway activity in vivo, GLI1 immunohistochemistry was performed
      on SCLC tumors. Interestingly, GLI1 was expressed in most SCLC tumors studied,
      indicating that HH signaling is important for in vivo growth of SCLC but
      establishment of cell lines from SCLC tumors may lead to loss of expression of
      key HH pathway members. Thus, the data support the idea that the HH pathway may
      be a therapeutic target in SCLC. However, the data also suggest that the SCLC
      cells can circumvent the apparent in vivo requirement of HH signaling.

PMID- 16616799
TI  - Blood pressure cuffs: friend or foe?
AB  - A study to assess the level of bacterial contamination of blood pressure cuffs in
      use on hospital wards was performed. Viable organisms were recovered from all the
      24 cuffs sampled at a density of between 1000 and >25 000 colony-forming
      units/100 cm2. Potential pathogens were isolated from 14 cuffs (58%). Eleven
      cuffs grew a single pathogen and three cuffs grew a mixture, yielding a total of
      18 isolates. Meticillin-susceptible Staphylococcus aureus was isolated from eight
      (33%) cuffs, meticillin-resistant S. aureus was isolated from two (8%) cuffs and
      Clostridium difficile was isolated from eight (33%) cuffs. This study serves as a
      reminder that hands are not the only fomite to go from patient to patient on
      hospital wards, and that measures should be taken to reduce the risks posed by
      blood pressure cuffs.

PMID- 16616800
TI  - A systematic review of the evidence for interventions for the prevention and
      control of meticillin-resistant Staphylococcus aureus (1996-2004): report to the
      Joint MRSA Working Party (Subgroup A).
AB  - A systematic review was undertaken of the evidence published between 1996 and
      2004 on the effectiveness, and associated economic costs, of a range of
      interventions to prevent and control the transmission of meticillin-resistant
      Staphylococcus aureus (MRSA) in hospital settings. The review questions focused
      on screening, patient isolation, use of decolonization strategies, feedback of
      surveillance data, and environmental hygiene interventions. The reviewers
      assessed evidence from four recent systematic reviews, 24 non-experimental
      descriptive studies, five economic evaluations and one recently revised
      international guideline. The methodological quality of studies retrieved was such
      that there is currently insufficient high-quality evidence for infection
      prevention and control interventions in the fields identified for this review.
      However, evidence from clinically based, non-experimental studies does provide
      support for the continued use of a range and combination of interventions that
      contribute to the prevention and control of MRSA within acute hospitals and long
      term-care settings. Well-conducted economic evaluations reporting the economic
      benefits arising from infection prevention and control interventions are lacking.

PMID- 16616801
TI  - Worms can alter T cell responses and induce regulatory T cells to experimental
      malaria vaccines.

PMID- 16616802
TI  - Reduction in morbidity of rotavirus induced diarrhoea in mice by yeast produced
      monovalent llama-derived antibody fragments.
AB  - Apart from the use of oral rehydration solution, there are currently no treatment
      modalities for rotavirus induced diarrhoea, which is particularly relevant to
      developing countries. Fragments derived from llama heavy chain antibodies were
      previously shown to be highly stable, efficiently produced in yeast and
      exhibiting high epitope specific affinity. We now aim to demonstrate that these
      antibody fragments are capable of reducing morbidity of rotavirus induced
      diarrhoea. Here we show the isolation of rotavirus specific antibody fragments
      and their capability of reducing the morbidity of rotavirus induced diarrhoea in
      vivo in mice. They could provide a treatment modality for the moderation of human
      rotavirus infections having a significant impact on the course of an often fatal
      childhood disease.

PMID- 16616803
TI  - Developing a vaccination evaluation model to support evidence-based decision
      making on national immunization programs.
AB  - Among all public health provisions national immunization programs (NIPs) are
      beyond doubt one of the most effective in reducing mortality, morbidity, and
      costs associated with major infectious diseases. To maintain their success, NIPs
      have to modernize in response to many new and old demands regarding efficacy,
      safety, availability of new vaccines, emerging and evolving pathogens, waning
      immunity, altered epidemiological situations, and the public's trust in the
      program. In this paper we present an evaluation model in the form of a checklist
      that may help in collecting relevant scientific information that is necessary for
      evaluation and decision making when considering changes in a NIP. Such a
      checklist points to relevant information on the vaccine-preventable disease, the
      pathogen causing it, the vaccine, and the cost-effectiveness ratio of the
      vaccine. However, the final judgment on a potential change in the NIP cannot be
      based on a simple algorithm, as the relevant information reflects factors of a
      very different kind and magnitude, to which different value judgements may be
      added, and which may have certain degrees of uncertainty. Because any change in
      the NIP may be accompanied by more or less unforeseen changes in the vaccine's
      efficacy, evolutionary consequences, including the antigenic composition of the
      pathogen, and the vaccine's safety profile, an intensive surveillance program
      should accompany any NIP. Elements thereof include clinical-epidemiological
      surveillance, surveillance of vaccination coverage, immune surveillance,
      surveillance of microbial population dynamics, and surveillance of adverse events
      and safety issues. We emphasize that the decision to introduce a vaccine in the
      NIP should be taken as seriously, both scientifically and ethically, as the
      decision to withhold a vaccine from the NIP. In the latter case one might be
      responsible for vaccine-preventable disease and mortality.

PMID- 16616804
TI  - Metal concentrations in edible mushrooms following municipal sludge application
      on forest land.
AB  - In the context of biosolids utilisation in forestry, effects of sludge
      application on mushroom metal concentration were studied in six sites of maritime
      pine forests in the South-West of France. Municipal sludge were applied at a rate
      of 6 T dry matter per hectare. Edible mushrooms were collected two years after
      sludge application. As, Cd, Cu, Hg, Pb, Se and Zn concentrations were determined.
      Results showed a high variability for trace element concentrations in mushrooms
      collected from control areas. No significant correlation was found between soil
      parameters (pH and trace elements concentrations) and mushroom trace element
      concentrations. Even if the concentration of trace metals increased in the soils,
      sludge application did not affect As, Cu, Se and Zn concentrations in carpophores
      but slightly increased Cd, Pb and Hg concentrations on some sites. This effect is
      dependent on sludge type and sites.

PMID- 16616805
TI  - EDDS and EDTA-enhanced phytoextraction of metals from artificially contaminated
      soil and residual effects of chelant compounds.
AB  - The potential of 18 different plants to be used in the chemically enhanced
      phytoextraction of Cu, Pb, Zn and Cd was assessed using pot experiments.
      Chrysanthemum coronarium L. was the species most sensitive to the application of
      EDTA, and had the highest enhancement of Cu and Pb concentrations in its shoots.
      Compared with EDTA, EDDS was more effective in enhancing the concentration of Cu
      in the shoots of Chrysanthemum coronarium L. and Zea mays L. grown on multi-metal
      contaminated soils. The EDTA-treated soil still had a significant ability to
      enhance the concentrations of Cu and Pb in the shoots of Zea mays L. six months
      after the chelant treatment. However, the EDDS-treated soil did not have any
      effect in enhancing the concentrations of metals in the shoots of Zea mays L. in
      the second crop test. The results may indicate that EDDS biodegrades more rapidly
      than EDTA in soil and is better in limiting potential metal leaching.

PMID- 16616806
TI  - Spatial variation in atmospheric nitrogen deposition on low canopy vegetation.
AB  - Current knowledge about the spatial variation of atmospheric nitrogen deposition
      on a local scale is limited, especially for vegetation with a low canopy. We
      measured nitrogen deposition on artificial vegetation at variable distances of
      local nitrogen emitting sources in three nature reserves in the Netherlands,
      differing in the intensity of agricultural practices in the surroundings. In the
      nature reserve located in the most intensive agricultural region nitrogen
      deposition decreased with increasing distance to the local farms, until at a
      distance of 1500 m from the local nitrogen emitting sources the background level
      of 15 kg N ha(-1) yr(-1) was reached. No such trend was observed in the other two
      reserves. Interception was considerably lower than in woodlands and hence
      affected areas were larger. The results are discussed in relation to the
      prospects for the conservation or restoration of endangered vegetation types of
      nutrient-poor soil conditions.

PMID- 16616807
TI  - Home is where the hearth is: grant recipients' views of England's home energy
      efficiency scheme (Warm Front).
AB  - This paper reports the results of research carried out as part of the national
      health impact evaluation of the Warm Front Scheme, a government initiative aimed
      at alleviating fuel poverty in England. Semi-structured interviews were carried
      out in a purposive sample of 49 households which received home energy
      improvements under the Scheme from five urban areas (Birmingham, Liverpool,
      Manchester, Newcastle, Southampton). Each household had received installation,
      replacement or refurbishment of the heating system and, in some cases, also
      insulation of the cavity wall or loft or both, and draught-proofing measures.
      Most householders reported improved and more controllable warmth and hot water.
      Many also reported perceptions of improved physical health and comfort,
      especially of mental health and emotional well-being and, in several cases, the
      easing of symptoms of chronic illness. There were reports of improved family
      relations, an expansion of the domestic space used during cold months, greater
      use of kitchens and improved nutrition, increased privacy, improved social
      interaction, and an increase in comfort and atmosphere within the home. Greater
      warmth and comfort also enhanced emotional security, and recipients were more
      content and at ease in their homes. However there was little evidence of
      substantially lower heating bills. These results provide evidence that Warm Front
      home energy improvements are accompanied by appreciable benefits in terms of use
      of living space, comfort and quality of life, physical and mental well-being,
      although there is only limited evidence of change in health behaviour.

PMID- 16616808
TI  - MK-1 expression in carcinoma of the ampulla of Vater as a predictor of improved
      prognosis after surgical resection.
AB  - This retrospective study investigated the prognostic significance of MK-1
      expression in human carcinoma of the ampulla of Vater (CAV). Expression was
      examined immunohistochemically using specimens from 38 patients who underwent
      surgical treatment for CAV. Expression was found in 61% of samples. Thirteen of
      15 well-differentiated but only two of eight poorly differentiated adenocarcinoma
      were positive (P=0.0352). MK-1 positivity tended to show significantly decreasing
      pT (P=0.0039), pN (P<or=0.001), and pStage (P=0.001). Multivariate analysis
      showed that MK-1 expression is an independent prognostic marker (P=0.0097) and
      Kaplan-Meier curves showed a significant relationship with increased overall
      survival (P=0.0137). These results suggest that MK-1 expression is a prognostic
      marker of CAV.

PMID- 16616809
TI  - Bladder cancer and mate consumption in Argentina: a case-control study.
AB  - Mate is a 'tea', made from Ilex paraguariensis, widely consumed in South America,
      as mate con bombilla and mate cocido. Mate consumption has been associated with
      esophageal, oral, lung, and bladder cancers. This bladder cancer case-control
      study involved 114 Argentinean case-control pairs. Mate consumption was recorded
      for time of interview, and 20 and 40 years previously. Mate con bombilla consumed
      20 years ago was associated with bladder cancer in ever-smokers (odds ratio=3.77,
      95% confidence interval: 1.17-12.1), but not in never-smokers. Mate cocido was
      not associated with bladder cancer. These results are consistent with a previous
      study in Uruguay.

PMID- 16616810
TI  - Effect of inducible FHIT and p53 expression in the Calu-1 lung cancer cell line.
AB  - Loss of FHIT expression and p53 mutations are critical events in the early stages
      of lung carcinogenesis. The restoration of Fhit function in FHIT-negative cancer
      cells has been reported to cause tumour suppression by inhibition of cell
      proliferation and/or activation of apoptotic pathways. However, the studies
      designed to elucidate the biological role of Fhit and its potential interaction
      with p53 have produced conflicting results. We investigated here the effects of
      the simultaneous restoration of FHIT and p53 in Calu-1 cells by using a hormone
      inducible gene expression system. We demonstrate that the restoration of FHIT
      expression reinforces the anti-proliferative effect associated with the
      simultaneous replacement of p53. Indeed, a more pronounced inhibition of cell
      proliferation associated with an earlier and higher induction of p21(waf1) mRNA
      and protein expression was observed in Fhit/p53-expressing cells compared with
      cells expressing p53 alone. This effect was not due to Fhit-mediated up
      regulation of p53 expression; in fact p53 protein was expressed at the same level
      in both FHIT-positive and FHIT-negative cell clones. Consistent with this result,
      Fhit did not affect the expression of MDM2, a protein known to interact directly
      with p53 and target p53 for proteolytic degradation, thus down-regulating its
      activity.

PMID- 16616811
TI  - The human Cyr61 gene is a transcriptional target of transforming growth factor
      beta in cancer cells.
AB  - Cyr61 is a multifunctional protein that can stimulate angiogenesis and tumor
      growth. Its expression by many cancers and breast cancers increases with tumor
      grade. Cyr61 is closely related to connective tissue growth factor, CTGF. Both
      proteins regulate skeletal development, suggesting that they could contribute to
      breast cancer metastases to bone, a process regulated by TGFbeta. We show that
      Cyr61 transcription is activated by TGFbeta and that the human Cyr61 promoter
      contains consensus sequences that bind Smad proteins. TGFbeta in the tumor
      microenvironment may stimulate cancer metastases to sites such as bone by
      increasing Cyr61 expression and secretion.

PMID- 16616812
TI  - Laboratory based approaches for arsenic remediation from contaminated water:
      recent developments.
AB  - Arsenic contamination in water has posed severe health problems around the world.
      In spite of the availability of some conventional techniques for arsenic removal
      from contaminated water, development of new laboratory based techniques along
      with enhancement and cost reduction of conventional techniques are essential for
      the benefit of common people. This paper provides an overview of the arsenic
      issue in water such as modes of contamination of ground water as well as surface
      water by arsenic, its metabolism and health impacts, factors influencing arsenic
      poisoning, fundamentals of arsenic poisoning mechanism and world scenario of
      arsenic poisoning. It discusses and compares the conventional laboratory based
      techniques, like precipitation with alum, iron, Fe/Mn, lime softening, reverse
      osmosis, electro dialysis, ion exchanges, adsorption on activated alumina/carbon,
      etc., for arsenic removal from contaminated water. It also discusses the best
      available techniques and mentions the cost comparison among these techniques too.
      Recent developments in the research on the laboratory based arsenic removal
      techniques, like improvement of conventional techniques and advances in removal
      technology along with its scopes and limitations have also been reviewed.

PMID- 16616813
TI  - Haycocknema-like nematodes in muscle fibres of a horse.
AB  - A 14-year-old horse (imported to Switzerland from Ireland 8 years earlier) showed
      signs of chewing muscle atrophy. A severe chronic myositis, caused by numerous
      immature and mature female nematodes, was diagnosed in muscle samples obtained by
      biopsy and subsequently at necropsy. Most of the nematodes had invaded muscle
      fibres of the masseter, root of the tongue and anterior breast, only a few were
      found in the intermuscular interstitium. Isolated nematodes and parasite sections
      were clearly different from muscle larvae of Trichinella spp. but showed
      morphological similarities to Haycocknema perplexum, a nematode species (order
      Enoplida, family Robertdollfusidae) recently found in the musculature of a human
      patient in Australia. However, our material did not allow the precise
      identification of the nematode genus nor the unequivocal differentiation from
      Halicephalobus gingivalis. This species infects horses and humans and can cause
      severe granuloma formation in muscles and many other organ systems, but has never
      been observed to invade individual muscle fibres. Our findings show that
      nematodes of another genus than Trichinella may invade muscle fibres of the horse
      and cause myositis. These nematodes are provisionally regarded as Haycocknema
      like.

PMID- 16616814
TI  - Psychosocial stress affects energy balance in mice: modulation by social status.
AB  - Stress has been associated with changes in eating behaviour and food preferences.
      Moreover, psychosocial and socio-economical challenges have been related with
      neuroendocrine-autonomic dysregulation followed by visceral obesity and
      associated risk factors for disease. In the current study, we provide a model of
      body weight development, food intake, energy expenditure of subordinate and
      dominant mice under psychosocial stress either in the presence of a standard diet
      or of a high palatable diet. When only standard chow was available stressed
      animals consumed more food in comparison to the control counterpart. Moreover,
      subordinate mice, at the end of the stress period were heavier in comparison to
      dominant animals. This last result was due to a decrease in the caloric
      efficiency of dominant animals in comparison to subordinates. Confirming this,
      the results of the experiment 2 showed that dominant mice significantly increase
      their energy expenditure at the end of the chronic psychosocial stress procedure
      in comparison to subordinate mice, as measured by indirect calorimetry. When a
      palatable high fat diet was available subordinate animals became heavier in
      comparison with both dominant and control animals. No differences in the caloric
      intake were found between groups. Subordinate mice ingested more calories from
      fat than controls, while dominant animals ingested more calories from
      carbohydrates. These results suggest that psychosocial stress can be a risk
      factor for overeating and weight gain in mice. However, social status influences
      the extent to which an individual keeps up with adverse environment, influencing
      the vulnerability toward stress related disorders.

PMID- 16616815
TI  - Gender differences in hypothalamic-pituitary-adrenal (HPA) axis reactivity.
AB  - The present study was designed to determine whether there are gender differences
      in hormonal response patterns to HPA axis activation. To this end, two methods of
      activating the HPA axis were employed: a standardized psychological stress test
      and a pharmacological challenge. Healthy subjects (mean age 23.4 years, SD 7.0
      years) completed a naloxone challenge and/or the modified Trier Social Stress
      Test (TSST). For the naloxone challenge, two baseline blood samples were
      obtained. Placebo was then administered (0 min), followed by increasing doses of
      intravenous naloxone (50, 100, 200 and 400 microg/kg) at 30-min intervals. Post
      placebo blood samples were collected at 15-min intervals for 180 min. The TSST
      consisted of 5 min of public speaking followed by 5 min of mental arithmetic
      exercises. Three baseline and five post-TSST blood samples were drawn. Eighty
      subjects (53 male, 27 female) underwent the TSST. Following the psychological
      stressor, adrenocorticotropin (ACTH) and cortisol responses were significantly
      greater in male subjects compared to female subjects (z=-2.34, p=0.019 and z=
      2.12, p=0.034, respectively). Seventy-two subjects (52 male, 20 female) underwent
      HPA axis activation induced by naloxone. In contrast to the TSST, cortisol
      responses to the naloxone challenge were significantly greater in female subjects
      compared to male subjects (z=4.11, p<0.001). Forty-one subjects (25 male, 16
      female) completed both the TSST and naloxone challenge. In this subset, ACTH and
      cortisol responses to the TSST did not differ significantly by gender, although
      the effect size was moderate to large. Adrenocorticotropin and cortisol responses
      to the naloxone challenge were significantly greater in female subjects compared
      to male subjects (z=2.29, p=0.022 and z=4.34, p<0.001, respectively). In summary,
      male subjects had greater HPA axis responses to a psychological stressor than
      female subjects, and females had greater hormonal reactivity than males to
      pharmacological stimulation with naloxone. Such differences are of interest as
      potential contributors to gender differences in health risks.

PMID- 16616816
TI  - The natural history of college smoking: trajectories of daily smoking during the
      freshman year.
AB  - Although the initiation of cigarette use typically occurs prior to age 18, there
      is evidence for considerable change in smoking behavior after this age. College
      may be a particularly important period to study smoking because it is a time when
      adolescents transition into a new social context where substance use is
      normative. Using a longitudinal design, daily assessments of smoking were
      collected during the entire first year of college for a large cohort of freshman
      (N=496). Findings suggested a weekly cycle of smoking such that the probability
      of smoking was much higher on weekends (Friday and Saturday) than on remaining
      days of the week. In addition to this weekly cycle, there was an overall trend
      for smoking to decline over the course of the year. Substantial individual
      variability in levels of smoking was observed. These findings provide new
      insights into college smoking, and have implications for assessment, policy,
      intervention, and future directions for research.

PMID- 16616817
TI  - Effects of stimulus manipulations on visual categorization in pigeons.
AB  - Four pigeons were previously trained [Lazareva, O.F., Freiburger, K.L.,
      Wasserman, E.A., 2004. Pigeons concurrently categorize photographs at both basic
      and superordinate levels. Psychon. Bull. Rev. 11, 1111-1117] to classify color
      photographs into either their proper basic-level category (cars, chairs, flowers,
      or people) or a superordinate-level category (nominally natural or artificial).
      In Experiment 1, the same pigeons were shown either reflected or inverted
      versions of the training stimuli. Reflection had no effect on pigeons'
      classification behavior, whereas inversion impaired discrimination of all
      stimulus categories, except flowers, on the basic-level and superordinate-level
      tasks. Pixel matching analysis revealed that pattern matching played at most a
      minor role in the birds' categorization behavior. In Experiment 2, the pigeons
      were shown test stimuli that were either blurred or quartered and scrambled.
      Blurring impaired discrimination of cars, but had no effect on discrimination of
      people and flowers; scrambling impaired discrimination of people and flowers
      leaving discrimination of cars and chairs unaffected. These results suggest that
      categorization of flowers and people may be controlled primarily by the overall
      shape of the object rather than by local features, whereas categorization of cars
      and chairs may rely primarily on local features rather than the overall shape of
      the object.

PMID- 16616818
TI  - Polyethylene glycol-phosphatidylethanolamine conjugate (PEG-PE)-based mixed
      micelles: some properties, loading with paclitaxel, and modulation of P
      glycoprotein-mediated efflux.
AB  - Mixed micelles prepared of poly(ethylene glycol)2000-phosphatidyl ethanolamine
      conjugate (PEG(2000)-PE) and d-alpha-tocopheryl polyethylene glycol 1000
      succinate (TPGS) in 1:1 molar ratio have been investigated. Micelle formation was
      confirmed by NMR spectroscopy. CMC of the micelles was found to be 1.5 x 10(-5)M.
      Poorly soluble anti-cancer drug paclitaxel (PCL) was efficiently solubilized in
      15 nm non-toxic PEG-PE/TPGS micelles. PCL entrapment was quite stable with only
      about 20% of the incorporated drug released from micelles after 48 h at 37
      degrees C. In addition, PCL-containing PEG(2000)-PE/TPGS micelles were stable in
      vitro under various conditions modeling the physiological ones, in particular, at
      low pH values and in the presence of bile acids, which is especially important
      for their possible oral administration. Fluorescently labeled micelles
      demonstrated time-dependent internalization by human colon adenocarcinoma cell
      line, Caco-2. The internalization of PEG(2000)-PE/TPGS micelles loaded with P
      glycoprotein (P-gp) substrate, rhodamine-123 (RH-123), opposite to the
      internalization of the free RH-123, was not influenced by the inhibition of the P
      gp pump with verapamil hydrochloride, which assumes a P-gp-independent micelle
      internalization.

PMID- 16616819
TI  - A thermo- and pH-sensitive hydrogel composed of quaternized
      chitosan/glycerophosphate.
AB  - The quaternized chitosan was synthesized by the reaction of chitosan and
      glycidyltrimethylammonium chloride (GTMAC) and named as N-[(2-hydroxy-3
      trimethylammonium) propyl] chitosan chloride (HTCC). A novel hydrogel system
      composed of HTCC/glycerophosphate (HTCC/GP) with thermo- and pH-sensitivity was
      synthesized and used as an intelligent drug carrier. The formulation was solution
      below or at room temperature, which allowed it injectable and to incorporate
      living cells, proteins, enzymes or other therapeutic drugs easily. Once the
      surrounding temperature was up to 37 degrees C, the system was transformed to a
      non-flowing hydrogel, and the formed hydrogel can release the trapped drug as a
      function of pH values. The swelling behavior of the system and the release
      profiles of doxorubicin hydrochloride (DX) as a model drug at different pH values
      were investigated. At acidic condition the hydrogel dissolved and released drug
      quickly, while it absorbed water and released drug slowly at neutral or basic
      conditions. Hydrogel composed of chitosan hydrochloride and glycerophosphate
      (CS/GP) was also prepared to compare with HTCC/GP hydrogel. The HTCC/GP hydrogel
      in this study was transparent which made it suitable for some specific uses such
      as ocular drug formulation.

PMID- 16616820
TI  - Environmental-sensitive micelles based on poly(2-ethyl-2-oxazoline)-b-poly(L
      lactide) diblock copolymer for application in drug delivery.
AB  - Anticancer drug doxorubicin (DOX) was physically loaded into the micelles
      prepared from poly(2-ethyl-2-oxazoline)-b-poly(L-lactide) diblock copolymers
      (PEOz-PLLA). PEOz-PLLA consists of hydrophilic segment PEOz and hydrophobic
      segment PLLA showed pH-sensitivity in the aqueous solution. The DOX-loaded
      micelle exhibited a narrow size distribution with a mean diameter around 170 nm.
      The micellar structure can preserve hydrophobic drug DOX under the physiological
      condition (pH 7.4) and selectively release DOX by sensing the intracellular pH
      change in late endosomes and secondary lysosomes (pH 4-5). At 37 degrees C, the
      cumulated released rate of DOX from micelles was about 65% at pH 5.0 in the
      initial 24 h. Additionally, polymeric micelles had low cytotoxicity in human
      normal fibroblast HFW cells for 72 h by using MTT assay. Moreover, DOX-loaded
      micelles could slowly and efficiency decrease cell viability of non-small-cell
      lung carcinoma CL3 cells. Taken together, PEOz-b-PLLA diblock polymeric micelles
      may act as useful drug carriers for cancer therapy.

PMID- 16616821
TI  - Age-associated tyrosine nitration of rat skeletal muscle glycogen phosphorylase
      b: characterization by HPLC-nanoelectrospray-tandem mass spectrometry.
AB  - We identified age-dependent post-translational modifications of skeletal muscle
      glycogen phosphorylase b (Ph-b), isolated from F1 hybrids of Fisher 344 x Brown
      Norway rats. Ph-b isolated from 34 months old rats showed a statistically
      significant decrease in specific activity compared to 6 months old animals:
      13.8+/-0.7 vs. 20.6+/-0.8 U mg(-1) protein, respectively. Western blot analysis
      of the purified Ph-b with anti-3-NT antibodies revealed an age-dependent
      accumulation of 3-nitrotyrosine (3-NT), quantified by reverse-phase HPLC-UV
      analysis to increase from 0.05+/-0.03 to 0.34+/-0.11 (mol 3-NT/mol Ph-b) for 6
      vs. 34 months old rats, respectively. HPLC-nanoelectrospray ionization-tandem
      mass spectrometry revealed the accumulation of 3-NT on Tyr113, Tyr161 and Tyr573.
      While nitration of Tyr113 was detected for both young and old rats, 3-NT at
      positions 161 and 573 was identified only for Ph-b isolated from 34 months old
      rats. The sequence of the rat muscle Ph-b was corrected based on our protein
      sequence mapping and a custom rat PHS2 sequence containing 17 differently located
      amino acid residues was used instead of the database sequence. The in vitro
      reaction of peroxynitrite with Ph-b resulted in the nitration of multiple Tyr
      residues at positions 51, 52, 113, 155, 185, 203, 262, 280, 404, 473, 731, and
      732. Thus, the in vitro nitration conditions only mimic the nitration of a single
      Tyr residue observed in vivo suggesting alternative pathways controlling the
      accumulation of 3-NT in vivo. Our data show a correlation of age-dependent 3-NT
      accumulation with Ph-b inactivation.

PMID- 16616822
TI  - Pulmonary nodule characterization: a comparison of conventional with quantitative
      and visual semi-quantitative analyses using contrast enhancement maps.
AB  - PURPOSE: To determine whether conventional nodule densitometry or analysis based
      on contrast enhancement maps of indeterminate lung nodules imaged with contrast
      enhanced CT can distinguish benign from malignant lung nodules. MATERIALS AND
      METHOD: Thin section, contrast-enhanced CT (baseline, and post-contrast series
      acquired at 45, 90,180, and 360 s) was performed on 29 patients with
      indeterminate lung nodules (14 benign, 15 malignant). A thoracic radiologist
      identified the boundary of each nodule using semi-automated contouring to form a
      3D region-of-interest (ROI) on each image series. The post-contrast series having
      the maximum mean enhancement was then volumetrically registered to the baseline
      series. The two series were subtracted volumetrically and the subtracted voxels
      were quantized into seven color-coded bins, forming a contrast enhancement map
      (CEM). Conventional nodule densitometry was performed to obtain the maximum
      difference in mean enhancement values for each nodule from a circular ROI. Three
      thoracic radiologists performed visual semi-quantitative analysis of each nodule,
      scoring each map for: (a) magnitude and (b) heterogeneity of enhancement
      throughout the entire volume of the nodule on a five-point scale. Receiver
      operator characteristic (ROC) analysis was conducted on these features to
      evaluate their diagnostic efficacy. Finally, 14 quantitative texture features
      were calculated for each map. A statistical analysis was performed to combine the
      14 texture features to a single factor. ROC analysis of the derived aggregate
      factor was done as an indicator of malignancy. All features were analyzed for
      differences between benign and malignant nodules. RESULTS: Using 15 HU as a
      threshold, 93% (14/15) of malignant and 79% (11/14) of benign nodules
      demonstrated enhancement. The ROC curve when higher values of enhancement
      indicate malignancy was generated and area under the curve (AUC) was 0.76. The
      visually scored magnitude of enhancement was found to be less effective in
      distinguishing malignant from benign lesions, with an average AUC of 0.62. The
      visually scored pattern of enhancement was found to be more effective with an
      average AUC of 0.79. From the statistical analysis performed to combine the
      texture features to a single factor, the area under the ROC curve was 0.84.
      CONCLUSION: The present study suggests that visual semi-quantitative and
      quantitative characterization of contrast enhancement patterns may potentially
      enhance the discrimination between benign and malignant nodules. Further studies
      and correlation with pathologic material will be important to better understand
      the potential interplay between CT enhancement features, host stromal elements,
      and neovascularity that may contribute to these patterns.

PMID- 16616823
TI  - Mammographic and ultrasonographic comparison between intraoperative radiotherapy
      (IORT) and conventional external radiotherapy (RT) in limited-stage breast
      cancer, conservatively treated.
AB  - OBJECTIVE: Assess mammographic and echographic modifications in mild cases of
      breast cancer (suitable for conservative surgery) after intraoperatory radio
      treatment (IORT) as opposed to conventional post-operative radiotherapy (RT).
      MATERIALS AND METHODS: We report data from 45 patients in each group (IORT and
      RT). All patients were examined using the same mammographic and ecographic
      equipment at 6, 12 and 24 months after treatment. We focused on structural
      alterations, edema and others, and quantified them using pre-established
      (unbiased) protocols. Both patient examination and subsequent assessment of the
      results were performed by radiologists with exepertise in breast cancer
      evaluation. RESULTS: At 6 months, IORT patients showed slightly more pronounced
      structural distortions and oedema than RT patients; these differences became more
      apparent at 12 months, with the addition of fat necrosis and/or calcifications.
      These alterations were evident and consistent under both mammographic and
      ecographic examination, and became even more pronounced at 24 months. At this
      stage, RT patients showed minimal alterations of the tissue (apart from normal
      post-surgical scarring), whereas IORT patients showed virtually no improvement
      over the preceding 12-month period. CONCLUSION: We show radiological alterations
      in post-operative breast cancer are significantly more pronounced in patients
      treated with IORT as opposed to RT.

PMID- 16616824
TI  - Determination of desoxyepothilone B in nude mice plasma by liquid-liquid
      extraction and reversed-phase high-performance liquid chromatography.
AB  - A novel reversed-phase high-performance liquid chromatographic (HPLC) method has
      been established for the determination of a newly developed anti-cancer agent
      desoxyepothilone B (dEpo B) in nude mice plasma. The sample preparation involved
      deproteination of 200 microl of plasma sample first, followed by liquid-liquid
      extraction of the resultant supernatant with chloroform. The compound taxol was
      used as the internal standard. Chromatographic separations were carried out on a
      250 mm x 4.6 mm Zorbax SB-phenyl column with acetonitrile-0.25% orthophosphoric
      acid (50/50, v/v) as mobile phase and UV detection at 250 nm. For dEpo B and
      taxol at the concentration level of 10 microg/ml in nude mice plasma, the
      absolute extraction recoveries were 85.3 and 87.2%, respectively. The linear
      quantification range of the method was 0.1-100 microg/ml in nude mice plasma with
      linear correlation coefficients greater than 0.999. The within-day and between
      day relative standard deviations (R.S.D.s) for dEpo B at 0.5, 2.5 and 10
      microg/ml levels in nude mice plasma fell in the range of 2.8-4.8 and 1.5-4.6%,
      and the within-day and between-day recoveries were in the range of 96.5-101.7 and
      97.7-101.2%, respectively.

PMID- 16616825
TI  - Coupling microdialysis with flow-injection chemiluminescence detection for a
      protein-drug interaction study.
AB  - The interaction of metronidazole (MTZ) and human serum albumin (HSA) was studied
      using the coupling system of on-line microdialysis sampling with flow-injection
      chemiluminescence detection (FI-MD-CL). The interested drug and HSA were mixed in
      different molar ratios in 0.067 mol L(-1) phosphate buffer (pH 7.4) and incubated
      at 37 degrees C in a water-bath. Then the microdialysis probe was put into the
      MTZ-HSA mixed solution and sampled at a perfusion rate of 5 microL min(-1). The
      microdialysates was determined using flow-injection chemiluminescence. In vitro
      recovery (R) of MTZ under experimental conditions was approximately 25.2% with a
      R.S.D. of about 3.2%. The values estimated for the binding constant (K) and the
      number of the binding sites (n) were found to be 1.50 x 10(3)L mol(-1) and 1.89,
      respectively. The values of nK obtained using Scatchard analysis and Klotz plot
      were found to be quite similar. The method provided a reliable and simple
      technique for the study of drug-protein interaction.

PMID- 16616826
TI  - Determination of nitrotyrosine and tyrosine by high-performance liquid
      chromatography with tandem mass spectrometry and immunohistochemical analysis in
      livers of mice administered acetaminophen.
AB  - Nitrotyrosine (NTYR) is used as a biomarker of nitrative pathology caused by
      peroxynitrite (ONOO-) formation. NTYR measurement in biological materials usually
      employs such methodologies as immunohistochemistry staining, high-performance
      liquid chromatography and gas chromatography. In this study, we developed a
      method for the determination of tyrosine (TYR) and NTYR, using liquid
      chromatography with tandem mass spectrometry (LC-MS/MS). In order to confirm the
      applicability of our method to an in vivo system, we measured protein-bound NTYR
      levels using by LC-MS/MS method and immunohistochemical analysis in liver of
      B6C3F1 mice at 2 h, 4 h and 8 h after administration of 300 mg/kg acetaminophen
      (APAP). A mass spectrometer equipped with an electrospray ionization source using
      a crossflow counter electrode and ran in the positive ion mode (ESI+) was set up
      for multiple reaction monitoring (MRM), which monitored the transitions
      182.2>136.2, 227.1>181.2, 191.3>144.4 and 236.3>189.5, for TYR, NTYR, [13C9]-TYR
      and [13C9]-NTYR, respectively. The average recoveries from mice liver protein
      samples spiked with 25 microM TYR and 100 nM NTYR were 94.4% and 95.6%,
      respectively, with correction using the added surrogate standards. The limits of
      quantification were 100 nM for TYR and 0.5 nM for NTYR. NTYR was detected all
      liver samples of mice by the proposed LC-MS/MS method. The concentration range of
      NTYR per milligram protein in samples was 0.17-0.3 pmol/mg protein. And the level
      reached a maximum at 4 h. These data were well correlated with the result
      obtained by an immunohistochemical reaction with anti-NTYR antibody. The LC-MS/MS
      method was able to determine protein-bound NTYR in a small amount of tissue
      sample, and is therefore expected to be a very powerful tool for evaluating ONOO-
      generation in an in vivo system.

PMID- 16616827
TI  - Systemic chemotherapy in the management of malignant peritoneal mesothelioma.
AB  - AIM: To review available evidence on the efficacy of chemotherapy in malignant
      mesothelioma of any origin. METHODS: All original research and review papers
      related to the role of systemic chemotherapy in the treatment of malignant
      mesothelioma, published from 1966 through February 2005, were identified through
      a MEDLINE search of the literature using the following search terms:
      "mesothelioma", "peritoneal", "chemotherapy", "antifolates", "cancer therapy".
      This search was supplemented by a manual search of the Proceedings of the Annual
      Meetings of the American Association for Cancer Research, American Society of
      Clinical Oncology, and the American Association for Cancer Research (AACR)
      European Organization for Research and Treatment of Cancer (EORTC)-National
      Cancer Institute (NCI) Symposium on New Anticancer Drugs. RESULTS: Pemetrexed in
      combination with cisplatin is the first treatment regimen that demonstrates a
      survival improvement in patients with unresectable malignant pleural
      mesothelioma. Data from uncontrolled studies suggest similar antineoplastic
      efficacy in patients with mesothelioma of peritoneal origin. Preliminary results
      also suggest a possible survival advantage for a combination of cisplatin and
      raltitrexed as compared to cisplatin alone. Other cytotoxic agents that have
      shown to be active in this setting include vinorelbine and gemcitabine, either
      alone or combined with platinum compounds. CONCLUSION: The pemetrexed-cisplatin
      combination has become the new standard of care for patients with unresectable
      malignant mesothelioma. Future strategies shall incorporate these novel agents
      into multimodality approaches at earlier stages of the disease. Given the low
      incidence of this disease, encouraging physicians to refer these patients to
      specialized centers and patients to participate in clinical trials is of utmost
      importance.

PMID- 16616828
TI  - IKKalpha stabilizes cytosolic beta-catenin by inhibiting both canonical and non
      canonical degradation pathways.
AB  - Beta-catenin is a bi-functional protein. It is not only a major component of the
      cellular adhesion machinery, but is also a transcription co-activator of the Wnt
      signaling pathway. The cytosolic levels of the beta-catenin protein, as well as
      its subcellular localization, are tightly regulated due to its oncogenic
      potentials. Two independent pathways are found to regulate beta-catenin. The
      canonical pathway is induced by the Axin/adenomatous polyposis coli
      (APC)/glycogen synthase kinase-3beta (GSK-3beta) complex which is dependent on
      GSK-3beta phosphorylation. The non-canonical pathway is mediated by p53-induced
      Siah-1 which is GSK-3beta phosphorylation-independent. Recently, several studies
      reported that IkappaB kinase alpha (IKKalpha) could stabilize beta-catenin and
      stimulate beta-catenin/T cell factor (Tcf)-dependent transcription. Here we
      report that IKKalpha could inhibit beta-catenin degradation mediated not only by
      the Axin/APC/GSK-3beta complex, but also by the Siah-1 pathway. Consistently, we
      found that IKKalpha abolished the inhibition of beta-catenin/Tcf-dependent
      transcription by Siah-1. Furthermore, we found that IKKalpha interacted with beta
      catenin and inhibited beta-catenin ubiquitination. Taken together, our results
      provide a new insight into IKKalpha-mediated beta-catenin stabilization.

PMID- 16616829
TI  - Effect of intracerebroventricular continuous infusion of valproic acid versus
      single i.p. and i.c.v. injections in the amygdala kindling epilepsy model.
AB  - Two protocols were tested to assess anticonvulsant efficacy and drug
      concentrations after intracerebroventricular (i.c.v.) continuous valproic acid
      (VPA) infusion, as compared with acute injections in the kindling epilepsy model.
      Protocol 1: amygdala-kindled rats were injected via intraperitoneal (i.p.) and
      i.c.v. routes with varying doses of VPA and tested for seizure intensity,
      afterdischarge and seizure duration, ataxia and sedation. Concentrations of VPA
      were determined by immunofluorescence in the brain, plasma, cerebrospinal fluid
      (CSF) and liver in matching rats. Protocol 2: amygdala-kindled rats were
      implanted with osmotic minipumps containing a VPA solution in saline and
      connected to intraventricular catheters for 7 days. Seizure threshold, latency
      and duration, afterdischarge duration, ataxia and sedation were recorded daily
      before, during, and until 5 days after VPA infusion. In matching animals, CSF,
      brain, plasma and liver VPA concentration was determined. Acute i.c.v. VPA
      injection suppressed seizures with a remarkable ataxia and sedation. However,
      continuous i.c.v. infusion controlled generalised and even focal seizures without
      producing important side effects, high plasma levels or hepatic drug
      concentrations. In conclusion, continuous i.c.v. VPA infusion may protect against
      kindled seizures by minimising ataxia and sedation, and achieving suitable
      intracerebral, yet low plasma or hepatic drug concentrations, thus avoiding
      potential systemic toxicity.

PMID- 16616830
TI  - Association of anticonvulsant hypersensitivity syndrome with Herpesvirus 6, 7.
AB  - BACKGROUND: Anticonvulsant hypersensitivity syndrome (AHS) is one of the most
      severe forms of drug eruption with potentially lethal, and multiorgan
      involvement. Recently, it has been suggested that Human Herpesvirus (HHV)
      infection has been involved in this syndrome, although the pathogenesis of this
      syndrome remains still unclear. METHODS: The objective of this study was to
      determine the clinical characteristics of AHS and the possible role of viral
      infection as a co-factor. We prospectively analyzed clinical, laboratory and
      virological findings for 23 cases of AHS. A viral study including viral serology
      and a polymerase chain reaction (PCR) was performed. RESULTS: The most common
      anticonvulsant was carbamazepine (12) followed by phenytoin (6), phenobarbital
      (4) and gabapentin (1). All patients met fulfill the clinical criteria of AHS.
      Even though internal organ involvement such as liver (52%), kidney (34%), and
      lung (13%) has been observed, involvement of heart, lung, thyroid, muscle,
      pancreas, spleen, and brain was less frequent. We also noted two patients who
      died due to multiorgan failure. No association with viral infection including
      HSV, VZV, HHV-8, CMV, EBV, measles, rubella and parvovirus B19 was detected in
      the current series. Increased serum anti-HHV-6 IgG and HHV-7 titers and presence
      of HHV-6 and -7 DNA in serum, revealed by PCR analysis, suggested reactivation of
      HHV-6. In contrast to the control groups, DNA for HHV-6 was detected in serum in
      5 out of the 23 patients while HHV-7 was seen in two patients. We found an
      evidence to link reactivation of HHV-6 or HHV-7 in the development of only
      carbamazepine-induced AHS. CONCLUSIONS: We propose that some cases of AHS are
      accompanied by reactivation of not only HHV-6 but also HHV-7. HHV infection may
      contribute to the severity, prolongation, or relapse of AHS and may possibly have
      fatal consequences in some susceptible individuals receiving the anticonvulsants.

PMID- 16616831
TI  - A comparison of cognitive structure in schizophrenia patients and healthy
      controls using confirmatory factor analysis.
AB  - There is evidence that cognitive task performance breaks down into the same broad
      domains in schizophrenia as in healthy populations. However, this does not mean
      that the domains are independent of one another or that the interrelationships
      among domains are the same between groups. We used confirmatory factor analysis
      (CFA) to compare the latent structure of a broad neuropsychological battery in
      schizophrenia patients (n = 148) and healthy controls (n = 157). Main analyses
      examined the fit of a hierarchical six-factor model, in which associations among
      the factors were assumed to reflect their strong shared relationship to a general
      cognitive ability factor. The model incorporated the factors of verbal
      comprehension, perceptual organization, verbal memory, spatial memory, processing
      speed, and executive/working memory. The hierarchical model provided a good
      overall fit to data from both groups. However multiple groups CFA revealed
      significant differences in factor loadings between groups, reflecting a more
      generalized latent structure of cognitive ability in schizophrenia. This was also
      evident in higher bivariate correlations among cognitive domain composite scores
      calculated from the observed test data. Cognitive ability, as reflected in test
      performance, appears to be more unitary in schizophrenia than in healthy
      subjects. This finding may have measurement and treatment implications.

PMID- 16616832
TI  - Neural dysfunction and violence in schizophrenia: an fMRI investigation.
AB  - Contemporary theories and evidence implicate frontal lobe dysfunction in violent
      behaviour as well as in schizophrenia. We applied functional magnetic resonance
      imaging (fMRI) to investigate and compare brain activation during an 'n-back'
      working memory task in groups of men with (i) schizophrenia and a history of
      serious physical violence (VS; n=13), (ii) schizophrenia without a history of
      violence (NVS: n=12), (iii) antisocial personality disorder (APD) and a history
      of serious physical violence (n=10), and (iv) no history of violence or a mental
      disorder (n=13). We observed comparable performance in all four groups during the
      control (0-back) condition. Subtle working memory deficits were seen in the NVS
      and APD groups but severe deficits emerged in the VS group relative to the
      healthy group. The VS group showed activation deficit bilaterally in the frontal
      lobe and precuneus when compared to the healthy group, and in the right inferior
      parietal region when compared to the NVS group during the working memory load
      condition. Frontal (bilateral) as well as right inferior parietal activity was
      negatively associated with the ratings of violence across all schizophrenia
      patients, with the right parietal region showing this association most strongly.
      APD patients, relative to healthy subjects, showed activation deficit in the left
      frontal gyrus, anterior cingulate and precuneus. It is concluded that reduced
      functional response in the frontal and inferior parietal regions leads to serious
      violence in schizophrenia perhaps via impaired executive functioning.

PMID- 16616833
TI  - Exogenously administered D-serine failed to potentiate the ability of MK-801 to
      antagonize electrically precipitated seizures in nonhandled control and stressed
      mice.
AB  - NMDA receptor hypofunction (NRH) has been implicated in the pathophysiology of
      schizophrenia because of the ability of phencyclidine (PCP), a noncompetitive
      NMDA receptor antagonist, to precipitate a schizophreniform psychosis. The
      possible role that NRH plays in the pathophysiology of schizophrenia stimulated
      characterization of behaviors elicited by PCP and its analogues. For example, MK
      801 (dizocilpine), a noncompetitive NMDA receptor antagonist that binds with
      higher affinity to the same hydrophobic channel domain as PCP, raises the
      threshold voltage required for the electrical precipitation of tonic hindlimb
      extension in mice. This ability of MK-801 is significantly reduced following
      stress. We showed that an exogenously administered glycine prodrug (i.e.,
      milacemide) was able to potentiate MK-801's antiseizure efficacy in unstressed
      mice and restore MK-801's antiseizure efficacy in stressed animals. d-Serine may
      serve as an endogenous agonist for the obligatory glycine co-agonist site on the
      NMDA receptor complex. Orally administered d-serine has been studied clinically
      as an adjuvant therapeutic intervention in schizophrenia. Thus, we were surprised
      at its inability to potentiate MK-801's antiseizure efficacy in either control or
      stressed animals. These data do not support the development of d-serine as a
      viable therapeutic intervention for schizophrenia and, possibly, other disorders.

PMID- 16616834
TI  - Background pathology of the common marmoset (Callithrix jacchus) in toxicological
      studies.
AB  - Two hundred common marmosets (Callithrix jacchus) from control groups (100 males,
      100 females) of toxicological studies were examined histopathologically to
      evaluate the spectrum of spontaneous lesions in this species. Frequent findings
      were extramedullary hematopoiesis affecting adrenal glands, liver, kidney and
      spleen, cystic Brunner's glands in the duodenum, acute or subacute inflammation
      in the large intestine and gall bladder, renal mineralization and pigmentation,
      hepatic Ito-cell vacuolation, microgranuloma and glycogen storage, pituitary
      cysts, C-cell hyperplasia and lymphocytic foci of the thyroid gland, luteal
      hyperplasia of the ovary and inflammatory cell foci in various organs.

PMID- 16616835
TI  - Assessment of chronic toxicity and carcinogenicity in an accelerated cancer
      bioassay in rats of Nifurtimox, an antitrypanosomiasis drug.
AB  - The chronic toxicity and carcinogenicity of Nifurtimox (NFX), a 5-nitrofuran
      derivative used in the treatment of American trypanosomiasis, were studied in
      male and female Wistar rats in an accelerated cancer bioassay (ACB). The ACB is a
      mechanistic initiation/promotion chronic toxicity and carcinogenicity bioassay
      designed to assess potential carcinogenic activity of a test substance in
      critical organs and tissues of rodents in which human carcinogens are active. The
      organs studied were liver, lungs, urinary bladder (UB), mammary gland (MG), bone
      marrow, spleen, kidneys, colon, stomach and any grossly observed lesions. NFX is
      a genotoxin which has been reported previously to exert a variable degree of
      carcinogenic activity in rat liver, kidney, UB and MG. The present study was
      undertaken to assess whether NFX has initiating activity in these four named
      target sites. In the initiation phase, groups of 20 Wistar rats were given NFX
      daily in the diet at 0.2% for the first 12 weeks of the study to assess
      initiating activity, followed by promoters (PROs) for four organs for an
      additional 24 weeks. NFX was compared to the following known initiators (INs) for
      each of these four tissues: diethylnitrosamine (DEN) for liver and kidney, N
      butyl-N(4-hydroxybutyl)nitrosamine (BBN) for UB and 7,12
      dimethylbenz(a)anthracene (DMBA) for MG. PROs included phenobarbital (PB) for
      liver and kidney, nitrilotriacetic acid (NTA) for UB, and diethylstilbestrol
      (DES) for MG. NFX was also administered continuously without PROs for 40 weeks.
      At the end of dosing (40 weeks) and at the end of recovery (52 weeks), animals
      were sacrificed and subjected to complete gross and histopathological
      examinations, along with evaluations of body weight gain over time and terminal
      body weights. Mortality was highest with DEN+PB (group 6) (40%), followed by
      BBN+NTA (group 7) (15%) and NFX+DES (group 5) and DMBA+DES (group 8) (10% each).
      The same groups also showed significant reductions in body weight gain over time
      and terminal body weights at sacrifice. In these groups, the expected
      preneoplastic, neoplastic and metastatic neoplastic lesions were produced,
      demonstrating the sensitivity of the model. In groups given NFX+PROs (groups 3
      5), either no neoplasms occurred (group 4) or only single neoplasms (groups 3 and
      5). In contrast, the PROs all elicited tumors in groups given INs (groups 6-8).
      Also, NFX given alone for 40 weeks did not produce any chronic toxicity,
      preneoplastic or neoplastic lesions. Thus, in this study, NFX did not demonstrate
      chronic toxicity or carcinogenicity. Moreover, in four target sites, i.e., liver,
      kidney, UB and MG, it exhibited no neoplastic initiating activity manifested by
      PROs for these four target sites.

PMID- 16616837
TI  - Molecular and physiological diversity among Verticillium fungicola var.
      fungicola.
AB  - The genetic and physiological variability of Verticillium fungicola var.
      aleophilum responsible for Agaricus bisporus dry bubble disease in North America
      is well documented but little is known about the var. fungicola affecting
      European crops. Variability was assessed within this variety and compared with
      that reported for the var. aleophilum. Eighteen isolates of V. fungicola var.
      fungicola and four var. aleophilum isolates were analysed for DNA polymorphism,
      mycelial growth, response to biochemicals produced by A. bisporus, fungicide
      resistance, and pathogenicity assessed by direct inoculation on sporophore or
      casing contamination. RAPD and AFLP markers delineated three French isolates from
      a homogeneous group containing the other var. fungicola isolates, but no
      correlation could be drawn between DNA polymorphism and the various traits
      studied. The var. fungicola isolates were more susceptible than the var.
      aleophilum isolates to the antibiosis effect of A. bisporus. Only mycelial growth
      rate at 23 degrees C could explain the variability in aggressiveness among the
      European isolates. The putative effect of the post-incubation temperature on
      contamination during mushroom cultivation was discussed. This work emphasized
      that, like the American var. aleophilum, the var. fungicola in Europe is
      genetically homogeneous, but physiological diversity exists, especially in France
      where it could be related to less standardized cultural practices.

PMID- 16616838
TI  - A new species of Phaeohelotium from Nothofagus forests in Argentina and Chile,
      with a key to the Southern Hemisphere species.
AB  - Phaeohelotium nothofagi, sp.nov., found on fallen wood and leaves of Nothofagus
      dombeyi, is described and illustrated. The fungus is characterized by pale yellow
      discs, and fumose ascospores with asperulate walls. A key with distributional
      data for the five species of the genus now known in the Southern Hemisphere is
      provided.

PMID- 16616839
TI  - Genetic population structure of three Armillaria species at the landscape scale:
      a case study from Swiss Pinus mugo forests.
AB  - Armillaria species are plant pathogens that cause Armillaria root rot and are
      known to cause mortality of mountain pines (Pinus mugo) in the Swiss National
      Park in the Central Alps. The identity of isolates and the spatially explicit
      population structure of the Armillaria species were investigated in a 3.3km(2)
      study area in the Swiss National Park. In total, 242 Armillaria isolates, 205
      from wood samples and 37 from epiphytic rhizomorphs, were collected. Species were
      identified using haploid-diploid pairings and genets were determined using
      intraspecific somatic incompatibility tests. The population structure differed
      markedly among the Armillaria species. A. cepistipes and A. borealis mainly
      occurred as genets of small spatial extent (mean 0.2ha, and 0.6ha), whereas A.
      ostoyae formed significantly larger genets (mean 6.8ha). The largest A. ostoyae
      genet extended over approx. 37ha. Several disease centres associated with
      Heterobasidion annosum were found to be embedded within large Armillaria genets.
      The extension of large A. ostoyae genets suggests that forests that occupy the
      study area have developed in the presence of these Armillaria genets. The finding
      of large Armillaria genets supports the assumption that large genets occur in
      areas with cold climate and little precipitation.

PMID- 16616840
TI  - Queirozia turbinata (Phyllactinieae, Erysiphaceae): a powdery mildew with a
      dematiaceous anamorph.
AB  - The powdery mildew monotypic genus Queirozia was reduced to a synonym of
      Pleochaeta in 1982. Now, a re-examination of the type material of Queirozia and
      of two other specimens showed that Queirozia turbinata has a very distinct
      combination of characters that do not allow its placement within Pleochaeta. It
      has forked special aerial hyphae, subclavate and predominantly lemon-shaped
      conidia, and both conidiophores and conidia varying from greyish to yellowish
      brown (a feature that appears to be unique for this fungus within the
      Erysiphales). This may represent the first dematiaceous anamorphic powdery mildew
      known to science. This fungus also has hemiendophytic mycelium, a character
      considered almost exclusive to the tribe Phyllactinieae. The outer wall surface
      pattern of wrinkled and turgid conidia of Q. turbinata as observed under the SEM
      is different from those presented in the literature for this tribe. Molecular
      analysis showed that Q. turbinata belongs to the tribe Phyllactinieae and is
      phylogenetic closer to Pleochaeta than to Leveillula or Phyllactinia. It is
      therefore acknowledged that Queirozia is closely related to Pleocheta but too
      distinct morphologically from this genus to be accepted as a synonym. Emended
      descriptions of Queirozia and Q. turbinata are presented.

PMID- 16616841
TI  - Molecular phylogeny of Acarosporaceae (Ascomycota) with focus on the proposed
      genus Polysporinopsis.
AB  - The molecular phylogeny of Acarosporaceae with a focus on the recently proposed
      genus Polysporinopsis was investigated using maximum parsimony and Bayesian
      analyses, using nuITS-LSU and mtSSU rDNA sequence datasets. A well-supported
      monophyletic clade corresponding to Acarospora (including the type species A.
      schleicheri, A. fuscata, A. nitrophila, A. rugulosa, A. bullata, A. sinopica, A
      molybdina and A. peliscypha) was present in all analyses. Acarospora as currently
      delimited is not monophyletic; neither A. smaragdula nor A. badiofusca belongs to
      the genus in the restricted sense. Polysporinopsis, which comprises three species
      previously classified in Acarospora (P. sinopica-type species, P. smaragdula, and
      P. rugulosa) is not a monophyletic group separate from Acarospora s. str.
      Acarospora sinopica and A. smaragdula are not closely related; A. sinopica
      belongs to Acarospora s. str., but A. smaragdula is one of the most basal taxa
      currently known in Acarosporaceae.

PMID- 16616842
TI  - Cloning and characterization of a cDNA encoding cholesterol side-chain cleavage
      cytochrome P450 (CYP11A1): tissue-distribution and changes in the transcript
      abundance in ovarian tissue of Japanese eel, Anguilla japonica, during
      artificially induced sexual development.
AB  - Cholesterol side-chain cleavage cytochrome P450 (CYP11A1: P450scc) is a crucial
      steroidogenic enzyme that catalyzes an initial step in the production of all
      classes of steroids. A cDNA encoding Japanese eel P450scc was cloned and
      characterized. The cDNA putatively encoded 521 amino acid residues with high
      homology to those of other vertebrate forms. The recombinant P450scc produced in
      COS-7 cells efficiently catalyzed the conversion of 25-hydroxycholesterol into
      pregnenolone. By northern blot, a single P450scc transcript of approximately 3.3
      kb was detected in both ovary and head kidney. Transcript levels of this enzyme
      significantly increased throughout ovarian development artificially induced by
      salmon pituitary homogenate, which suggests that gonadotropic stimuli can induce
      ovarian expression of the P450scc gene in teleosts, as has been reported in
      mammals. Furthermore, RT-PCR analysis revealed that gene expression of three
      steroidogenic enzymes, P450scc, P450c17 and 3beta-hydroxysteroid dehydrogenase
      (3beta-HSD) show distinctly different tissue-specific patterns of expression in
      the Japanese eel. The P450scc gene was expressed in ovary and head kidney while
      the sole source of the P450c17 transcript was ovary. In contrast, 3beta-HSD
      transcript was detected in all tissues examined, brain, liver, spleen and trunk
      kidney, etc. These suggest that some steroidogenic enzymes are also expressed in
      non-endocrine tissues and could potentially regulate the local and/or circulating
      steroid levels in teleosts, as they do in mammals.

PMID- 16616844
TI  - Polyneuropathies in teenagers: a clinicopathological study of 45 cases.
AB  - The aim of the present study was to investigate the causes of polyneuropathy in
      teenagers and to describe some characteristic clinical, laboratory,
      electrophysiological and pathological features. Forty-five patients with
      peripheral nervous disorders aged 13-19 were studied. Hereditary polyneuropathy
      of different types was diagnosed in 28 patients (62%); nine showed chronic
      inflammatory demyelinating polyneuropathy (CIDP) and two showed vasculitic
      neuropathy. In two more cases polyneuropathy was attributed to toxic agents,
      while among the rest, one was diagnosed as metachromatic leucodystrophy (juvenile
      type), one as adrenoleucodystrophy, one as porphyric neuropathy and one as Fabry
      disease. The high incidence of hereditary neuropathies in teenagers differs from
      that in adults, but is similar to that encountered in children. In our study,
      CIDP appears to be a frequent cause of neuropathy in teenagers, while the other
      causes are broadly similar to those found in studies concerning children rather
      than adults.

PMID- 16616843
TI  - Synthetic 19-nortestosterone derivatives as estrogen receptor alpha subtype
      selective ligands induce similar receptor conformational changes and steroid
      receptor coactivator recruitment than natural estrogens.
AB  - The binding of estradiol (E(2)) to estrogen receptors (ER) is followed by
      conformational changes resulting in coactivator or corepressor recruitment that
      influences gene transcription. A series of synthetic A-ring reduced 19
      nortestosterone-derived progestins has the capacity to selectively bind and
      activate transcription through the ERalpha. Herein, the molecular mechanisms
      involved in ER subtype-selective interactions of these compounds as assessed by
      their effects upon both ERalpha and ERbeta structural conformation and their
      ability to induce recruitment of steroid receptor coactivator-1 (SRC-1) to
      ERalpha were investigated. The results demonstrated that all synthetic A-ring
      3beta,5alpha-tetrahydro-reduced derivatives of 19-nortestosterone induced an
      ERalpha trypsin digestion pattern similar to that seen with E(2), without effects
      upon ERbeta. In addition, these compounds had the ability to recruit SRC-1 to the
      ligand-binding domain of ERalpha similar to E(2). Our data indicate that A-ring
      3beta,5alpha-tetrahydro-reduced 19-nortestosterone-derived progestins behave as
      selective ERalpha agonists with ligand-receptor structural and functional
      responses similar to those induced with natural E(2).

PMID- 16616845
TI  - Genetic heterogeneity within a consanguineous family involving the LGMD 2D and
      the LGMD 2C genes.
AB  - The sarcoglycanopathies are a group of autosomal recessive limb girdle muscular
      dystrophies (AR-LGMD 2) characterised by mutations in gene encoding one of the
      sarcoglycan subunits. Mutations in SGCA, SGCB, SGCG and SGCD genes are associated
      with LGMD 2D, 2E, 2C and 2F, respectively. We report three Tunisian patients
      belonging to the same consanguineous family sharing similar LGMD 2 phenotype but
      heterogeneous sarcoglycans immunohistochemical patterns. Linkage analysis
      suggests linkage with the LGMD 2D locus for the two siblings and with LGMD 2C
      locus for the third patient. Mutation analysis revealed two distinct mutations. A
      del521T homozygous mutation in exon 6 of the SGCG gene (LGMD 2C), widely
      distributed in Tunisian patients, was found in one patient, whereas a 157G>A
      homozygous mutation in exon 2 of the SGCA gene (LGMD 2D) was found in the two
      siblings. The presence of two distinct genetic forms, LGMD 2C and LGMD 2D in a
      consanguineous family raises the problem of the complexity of genetic counselling
      in inbred populations.

PMID- 16616846
TI  - AlOH3-adjuvanted vaccine-induced macrophagic myofasciitis in rats is influenced
      by the genetic background.
AB  - Macrophagic myofasciitis (MMF) is a specific histopathologic lesion involved in
      the persistence for years of aluminum hydroxide [Al(OH)(3)] at the site of
      previous intramuscular (i.m.) injection. In order to study mechanisms involved
      persistence of MMF lesions, we set up an experimental model of MMF-lesion in
      Sprague-Dawley and Lewis rat, by i.m. injections of 10 microL of an Al(OH)(3)
      adjuvanted vaccine. An evaluation carried out over a 12-month period disclosed
      significant shrinkage of MMF lesions with time. A radioisotopic study did not
      show significant aluminium uptake by Al(OH)(3)-loaded macrophages. A morphometric
      approach showed that Lewis rats with Th1-biased immunity had significantly
      smaller lesions than Sprague-Dawley rats with balanced Th1/Th2 immunity.
      Concluding, our results indicate that genetic determinatives of cytotoxic T-cell
      responses could interfere with the clearance process and condition the
      persistence of vaccine-induced MMF-lesions.

PMID- 16616847
TI  - Novel myelin protein zero mutation (Arg36Trp) in a patient with acute onset
      painful neuropathy.
AB  - We present a patient with acute onset painful polyneuropathy found to have a
      novel MPZ mutation (Arg36Trp). The Arg36Trp mutation described in this report
      occurs at a putative adhesion interface. An alternative explanation for his
      polyneuropathy was not found and his mother was identified to have polyneuropathy
      and carry the same mutation. Two hundred normal controls were without this base
      alteration. The temporal profile of the index case may provide further indirect
      evidence suggesting an immune mechanism contributing to the pathogenesis of some
      cases of MPZ mutations. We predict that other rapid symptom onset
      polyneuropathies will be found to have direct genetic susceptibility.

PMID- 16616848
TI  - Marked efficacy of a therapeutic strategy associating prednisone and plasma
      exchange followed by rituximab in two patients with refractory myopathy
      associated with antibodies to the signal recognition particle (SRP).
AB  - We report two patients with myopathy associated with anti-signal recognition
      particle Ab, refractory to conventional therapy, who were treated with prednisone
      and plasma exchange, followed by rituximab. A marked response was observed in
      both patients, with partial to complete recovery of muscle strength, which was
      sustained.

PMID- 16616849
TI  - Movin' on up: the role of PtdIns(4,5)P(2) in cell migration.
AB  - Cell migration requires the coordination of many biochemical events, including
      cell-matrix contact turnover and cytoskeletal restructuring. Recent advances
      further implicate phosphatidylinositol(4,5)-bisphosphate [PtdIns(4,5)P(2)] in the
      control of these events. Many proteins that are crucial to the assembly of the
      migration machinery are regulated by PtdIns(4,5)P(2). Coordinated synthesis of
      PtdIns(4,5)P(2) at these sites is dependent on the precise targeting of the type
      I phosphatidylinositol phosphate kinases (PIPKs). Two PIPKI isoforms target to,
      and generate, PtdIns(4,5)P(2) at membrane ruffles and focal adhesions during cell
      migration. Here, we discuss our current understanding of PtdIns(4,5)P(2) in the
      regulation of cell responses to migratory stimuli and how the migrating cell
      controls PtdIns(4,5)P(2) availability.

PMID- 16616850
TI  - Lethal giant larvae take on a life of their own.
AB  - Cell polarization requires the segregation of the plasma membrane into domains of
      distinct protein composition. The Lethal giant larvae (Lgl) protein of
      Drosophila, initially identified as a tumor suppressor, establishes such domains
      by localizing specific proteins to specific regions of the plasma membrane.
      However, how it does this remains puzzling and controversial. Recent studies of
      the yeast orthologs show a molecular pathway through which Lgl is activated
      locally to promote the targeted fusion of vesicles with the plasma membrane.
      Here, we reconcile these data with conflicting findings on the mechanism of Lgl
      in animals and consider if a similar model explains its role in epithelial
      polarity and asymmetric cell division.

PMID- 16616851
TI  - Bioenergetic abnormalities in discrete cerebral motor pathways presage spinal
      cord pathology in the G93A SOD1 mouse model of ALS.
AB  - Multiple cell death pathways are implicated in the etiology of amyotrophic
      lateral sclerosis (ALS), but the cause of the characteristic motor neuron
      degeneration remains unknown. To determine whether CNS metabolic defects are
      critical for ALS pathogenesis, we examined the temporal evolution of energetic
      defects in the G93A SOD1 mouse model of familial ALS. [14C]-2-deoxyglucose in
      vivo autoradiography in G93A mice showed that glucose utilization is impaired in
      components of the corticospinal and bulbospinal motor tracts prior to either
      pathologic or bioenergetic changes in the spinal cord. This was accompanied by
      significant depletions in cortical ATP content in presymptomatic mice, which was
      partially ameliorated by creatine administration. Findings suggest that
      bioenergetic defects are involved in the initial stages of mSOD1-induced toxicity
      in G93A mice and imply that the selective dysfunction and degeneration of spinal
      cord motor neurons in this model may be secondary to dysfunction within cerebral
      motor pathways.

PMID- 16616852
TI  - Concerning the Editorial comment by Dr Menicanti.

PMID- 16616854
TI  - Thinking beyond the risk factors.
AB  - For each risk factor for Black Death he discovered, John Graunt in 1662 made a
      recommendation for action, such as fleeing the night air brought to the City of
      London docks on foreign ships. These stopped the plague for 200 years! In this
      honored guest lecture, I focus on thinking beyond the risk factors to their
      neutralization by effective action without waiting for perfect knowledge of
      mechanisms. For example, the decreasing risk of repairing atrioventricular septal
      defect resulted from risk factors that stimulated focused research to devise a
      better operation. General reduction in risk reduced mortality of aortic valve
      replacement in patients with chronic aortic regurgitation and severe left
      ventricular dysfunction. Optimal timing of surgery after stabilizing patients
      reduced risk of the Norwood procedure. Managing intractable cardiogenic shock
      reduced risk-adjusted mortality in post-infarct ventricular septal defect.
      However, we must think beyond traditional risk factors to neutralization of those
      brought by patient characteristics, imponderables, treatment delivery systems,
      institutions delivering care to groups of patients, and society caring for its
      population. There are limitations to thinking beyond risk factors. First,
      neutralizing strategies require improving processes or introducing new ones. Yet
      there may be process-outcome disconnect, or even counterintuitive or
      contradictory relations among outcomes and what are thought to be best processes.
      Nevertheless, thinking beyond risk factors to their neutralization by research,
      innovation, and application of knowledge can be as spectacularly successful as
      was fleeing foul air in halting Black Death.

PMID- 16616855
TI  - Neutrophil transendothelial migration potential predicts rejection severity in
      human cardiac transplantation.
AB  - OBJECTIVE: Transplant rejection remains a clinical problem despite therapies that
      focus on lymphocyte suppression, with little attention focused on the neutrophil.
      Neutrophils are however the first leukocyte to infiltrate the allograft, are
      capable of causing myocardial damage and may facilitate lymphocytes recruitment.
      We hypothesised that an early allograft neutrophil infiltration influences
      rejection severity. METHODS: Myocardial neutrophil infiltration was assessed
      using CD15 and myeloperoxidase immunohistochemistry of rejection surveillance
      endomyocardial biopsy specimens from human cardiac transplant recipients (n=18).
      In patients undergoing cardiac transplantation (n=10), neutrophils were isolated
      from multiple perioperative blood samples using a ficoll-based density gradient
      centrifugation method. The expression of the neutrophil adhesion protein CD11b
      was then assessed using flow cytometry and compared to subsequent endomyocardial
      biopsy rejection grades. The effects of contemporary immunosuppressive agents on
      human neutrophil CD11b were also assessed using healthy control volunteers.
      RESULTS: Myeloperoxidase staining of endomyocardial biopsies from human heart
      transplant recipients demonstrated a positive correlation between the degree of
      neutrophil infiltration and rejection severity at the first postoperative biopsy.
      Rejection severity was unrelated to ischaemic time. Functional assessment of
      neutrophils obtained from recipients was then performed. Perioperative transplant
      sampling demonstrated a significant correlation between the preoperative
      expression of CD11b and rejection grade at the first postoperative biopsy. In
      addition, dynamic changes in CD11b expression in the first 24 h positively
      correlated with subsequent rejection severity. In vitro experiments showed that
      transplant immunosuppression did not alter neutrophil CD11b expression.
      CONCLUSION: This study demonstrates a potentially greater role for neutrophils in
      cardiac transplantation than previously recognised, and suggests that blockade of
      the early allograft neutrophil infiltration might prevent subsequent lymphocyte
      recruitment and attenuate rejection.

PMID- 16616856
TI  - The binding of BmK IT2 on mammal and insect sodium channels by surface plasmon
      resonance assay.
AB  - The binding of BmK IT2 to insect and mammal sodium channels was investigated by
      surface plasmon resonance technique. The results showed that BmK IT2 could bind
      not only to cockroach neuronal membranes but also to rat cerebrocortical and
      hippocampal synaptosomes with distinct affinity. The binding of BmK IT2 could be
      competed significantly by BmK AS and BmK abT, but not by AaH II, BmK I and
      veratridine. Furthermore, BmK alphaIV could partially inhibit the binding of BmK
      IT2 to rat cerebrocortical synaptosomes and cockroach neuronal membranes, but not
      to rat hippocampal synaptosomes. These results suggested that BmK IT2 had diverse
      binding properties on the mammal and insect sodium channels.

PMID- 16616857
TI  - Thalidomide alters c-MYB and PIM-1 signaling in K-562 cells.
AB  - Despite causing birth defects thalidomide is being used therapeutically to treat
      a number of diseases. While thalidomide's mechanism of action still remains
      unknown, exposure to thalidomide leads to increased reactive oxygen species
      (ROS), which can interfere with cell signaling. We hypothesize that thalidomide
      acts by interfering with the c-Myb signaling pathway. To investigate this
      hypothesis, human K-562 cells were transfected with plasmids expressing a Myb
      responsive luciferase reporter and c-Myb. Cells were then exposed to thalidomide
      (0 or 40 microg/ml) for 1h and luciferase activities were measured. Cells exposed
      to thalidomide (40 microg/ml) had significantly decreased c-Myb activity. Pre
      incubation of cells with the anti-oxidative enzyme catalase (1600 units/ml),
      prevented thalidomide-induced decreased c-Myb activity, suggesting a role for ROS
      in the c-Myb signaling pathway. This result was further substantiated by the
      dichlorofluorescein assay. Western blot analysis on thalidomide exposed cells
      showed a decrease in both Pim-1 protein expression and phosphorylated c-Myb
      protein expression, suggesting that the decrease in Pim-1 and the amount of
      phosphorylated c-Myb protein may be responsible for the observed decreases in c
      Myb activity. Together these results demonstrate that thalidomide affects c-Myb
      signaling, in part, through increased ROS production.

PMID- 16616858
TI  - Fragmentation of peptides with N-terminal dimethylation and imine/methylol
      adduction at the tryptophan side-chain.
AB  - The reaction between formaldehyde and the side-chain of tryptophan results in a
      methylol adduct. This methylol adduct formation also occurs during reductive
      methylation reactions. In the current study, we investigate the fragmentation
      pattern of peptides with N-terminal dimethylation and methylol adduction at the
      tryptophan side-chain. Once formed, the methylol group can easily undergo water
      loss to form an imine. The peptides with imine or methylol adduct on tryptophan
      exhibit similar MS/MS fragmentation patterns. We observed ions resulting from an
      intramolecular reaction between the dimethylamino group at the peptide N-terminus
      or the lysine side-chain and the imine group. This reaction reduces the imine to
      a methyl group. We also observed the loss of the imine adduct on tryptophan. This
      reaction is likely to occur through the reaction of an amino or hydroxyl group
      with the imine adduct followed by subsequent loss of methylenimine or
      formaldehyde.

PMID- 16616859
TI  - MALDI-TOF MS as a label-free approach to rapid inhibitor screening.
AB  - Mass Spectrometry (MS) has been widely reported for measuring the conversion of
      substrates to products for enzyme assays. These measurements are typically
      performed by time-consuming LC-MS to eliminate buffer salts that interfere with
      electrospray ionization MS. However, matrix-assisted laser desorption ionization,
      time-of-flight MS (MALDI-TOF MS) offers a label-free and direct readout of
      substrate and product, a fast sampling rate, and is tolerant of many buffer
      salts, reagents, and compounds that are typically found in enzyme reaction
      mixtures. In this report, a demonstration of how MALDI-TOF MS can be used to
      directly measure ratios of substrates and products to produce IC(50) curves for
      rapid enzyme assays and compound screening is provided. Typical reproducibility
      parameters were <7% RSD-a value comparable to ESI MS quantitative assays and well
      within the acceptable limits for screening assays. The speed of the MALDI readout
      is currently about 10 s per sample, thus allowing for over 7500 samples/day. From
      a simplicity standpoint, the enzymatic reaction mixtures are prepared by liquid
      handling robots, the reactions are stopped by addition of a 10 times volume of
      acidic matrix solution, and the samples are simultaneously transferred to MALDI
      target plate for analysis. Importantly, the ratios of substrate to product are of
      sufficient reproducibility to eliminate the need for internal standards and,
      thus, minimize the cost and increasing the speed of assay development.

PMID- 16616860
TI  - Effect of buffer gas on the fluorescence yield of trapped gas-phase ions.
AB  - We investigated the dependence of three different gases, helium, argon, and
      nitrogen, on the fluorescence signal intensity of rhodamine 6G cations in the gas
      phase. The method is based on laser-induced fluorescence of ions trapped in a
      Fourier transform ion cyclotron mass spectrometer. We found that the use of
      helium results in the highest fluorescence signal, while no fluorescence was
      detected when using argon under the same conditions.

PMID- 16616861
TI  - Electron capture dissociation of peptides metalated with alkaline-earth metal
      ions.
AB  - The possible use of divalent alkaline-earth metal ions, including Mg2+, Ca2+,
      Sr2+, and Ba2+, as charge carrier for electron capture dissociation of peptides
      was investigated. Model peptides of RGGGVGGGR and NGGGWGGGN were used to simplify
      the interpretation of spectral information. It was demonstrated that useful
      electron capture dissociation (ECD) tandem mass spectra of these metalated
      peptides could be generated. Interestingly, peptides metalated with different
      alkaline-earth metal ions generated very similar ECD tandem mass spectra.
      Metalated c-ions and z-ions were the predominant fragment ions. Only Mg2+
      metalated peptides gave somewhat different results. Some nonmetalated c-ions were
      observed from ECD of [RGGGVGGGR + Mg]2+ but not from [NGGGWGGGN + Mg]2+. Together
      with some ab initio calculations, it was established that the bound metal ions
      might activate the acidity of the amide hydrogen. With the presence of high
      proton affinity moiety, such as N-terminal amino group and/or side chain of the
      arginine residues, the metalated peptide ions could exist predominantly in their
      zwitterion forms, in which one or two backbone amide group(s) was deprotonated
      and the high proton affinity functional group(s) was protonated. It was believed
      that electron capture leads primarily to the reduction of the mobile proton
      rather than the metal ions. With this zwitterion model, the formation of
      nonmetalated c-fragments and the generation of similar ECD spectra for peptides
      metalated with various alkaline-earth metal ions could readily to be explained.
      Another interesting observation in the ECD mass spectra of metalated peptides is
      related to the enhanced formation of the minor ECD products, i.e., (c - 1)(+*)
      and (z + 1)+ ions. Together with ab initio calculations using a truncated peptide
      model, various possible reaction mechanisms for the formation of these minor ECD
      products were evaluated. It was concluded that hydrogen transfer between the
      initiated formed c and z(.) species plays an important role in the formation (c -
      1)(+*) and (z + 1)+ ions. Although peptides metalated with these metal ions do
      not have better ECD efficiency compared to the multiply-protonated peptides, it
      provides practical accessibility of ECD methods to analyze small peptides with no
      basic amino acid residues.

PMID- 16616862
TI  - Attention does not modulate neural responses to social stimuli in autism spectrum
      disorders.
AB  - We investigated whether individuals with autism spectrum disorders (ASD) would
      show attentional modulation for social (face) and non-social (house) stimuli.
      Sixteen individuals with ASD and 16 matched control participants completed a task
      in which pairs of face and house stimuli were present on every trial, with one of
      the pairs randomly assigned to attended locations and the other to unattended
      locations. Both mass-univariate (SPM) and region of interest analyses suggested
      that responses to houses were modulated by attention in both groups, but that
      only the control participants demonstrated attentional modulation of face
      selective regions. Thus, the participants with ASD demonstrated a lack of
      attentional modulation which was particularly evident for the social stimulus.
      Analyses of effective connectivity indicated that these results were due to a
      failure of attention to modulate connectivity between extrastriate areas and V1.
      We discuss how these results may suggest a mechanism to explain the reduced
      salience of social stimuli in ASD.

PMID- 16616863
TI  - The neural mechanism associated with the processing of onomatopoeic sounds.
AB  - This event-related fMRI study was conducted to examine the blood-oxygen-level
      dependent responses to the processing of auditory onomatopoeic sounds. We used a
      sound categorization task in which the participants heard four types of stimuli:
      onomatopoeic sounds, nouns (verbal), animal (nonverbal) sounds, and pure
      tone/noise (control). By discriminating between the categories of target sounds
      (birds/nonbirds), the nouns resulted in activations in the left anterior superior
      temporal gyrus (STG), whereas the animal sounds resulted in activations in the
      bilateral superior temporal sulcus (STS) and the left inferior frontal gyrus
      (IFG). In contrast, the onomatopoeias activated extensive brain regions,
      including the left anterior STG, the region from the bilateral STS to the middle
      temporal gyrus, and the bilateral IFG. The onomatopoeic sounds showed greater
      activation in the right middle STS than did the nouns and environmental sounds.
      These results indicate that onomatopoeic sounds are processed by extensive brain
      regions involved in the processing of both verbal and nonverbal sounds. Thus, we
      can posit that onomatopoeic sounds can serve as a bridge between nouns and animal
      sounds. This is the first evidence to demonstrate the way in which onomatopoeic
      sounds are processed in the human brain.

PMID- 16616864
TI  - Design of compliance chamber and after-load in apparatus for cultured endothelial
      cells subjected to stresses.
AB  - In order to create a hemodynamic environment that can simulate the physiological
      condition of arteries, an in vitro experiment apparatus was designed whose key
      modules were compliance chamber and after-load. These two modules were developed
      based on the theories of hemodynamics. Both the normal and shear stress to which
      endothelial cells are exposed can be controlled with these modules, thus
      facilitating the research of endothelial cells subjected to stresses.

PMID- 16616865
TI  - Cadmium induced endothelial dysfunction: consequence of defective migratory
      pattern of endothelial cells in association with poor nitric oxide availability
      under cadmium challenge.
AB  - Recent advances in cadmium toxicity research suggest an association between
      cadmium and vascular diseases. However, the mechanisms of cadmium implications in
      vascular diseases are not yet explained. The objective of our present study is to
      explore the mechanism of cadmium induced endothelial dysfunction. Doses of 0, 1
      and 5microM cadmium chloride were used to test the effects of cadmium on nitric
      oxide induced tube formation, cellular migration and subcellular actin
      polymerization in ECV-304 endothelial cells. An egg-yolk vascular bed model was
      used to study the effects of cadmium on angiogenesis. Results of the present
      study show that 5microM cadmium chloride effectively inhibited angiogenesis,
      cellular migration and tube formation. Phalloidin staining, which represents
      actin polymerization of endothelial cells, reveals that cadmium induces an
      altered F-actin pattern, which could be the prime cause for cadmium mediated
      inhibition of cellular migration and angiogenesis. Cadmium was also found to
      inhibit nitric oxide production in endothelial cells in a calcium free medium,
      which further hints that cadmium might impair endothelial functions by inhibiting
      endothelial nitric oxide synthase.

PMID- 16616866
TI  - Src homology 2 domain of overexpressed Lyn kinase is responsible for the
      acceleration of granulocyte colony-stimulating factor-induced neutrophilic
      nuclear lobulation.
AB  - We have previously shown that the overexpression of a Src family kinase, Lyn, and
      its kinase-negative form, LynKN, in a granulocyte progenitor cell line, GM-I62M,
      accelerates neutrophilic nuclear lobulation when the cells are cultured in the
      presence of granulocyte colony-stimulating factor. In this study, we investigated
      the role of the Src homology 2 (SH2) and SH3 domains of Lyn in the accelerated
      induction of nuclear lobulation. In contrast to wild-type Lyn, the overexpression
      of its SH2 domain mutant did not induce the accelerated nuclear morphological
      changes, but the overexpressed SH3 domain mutant had the same effects as wild
      type Lyn. Therefore, the SH2 domain of Lyn is responsible for the accelerated
      induction of neutrophilic nuclear lobulation upon G-CSF stimulation.

PMID- 16616867
TI  - Human autologous serum obtained using a completely closed bag system as a
      substitute for foetal calf serum in human mesenchymal stem cell cultures.
AB  - The major problem in cell therapy is the possibility of viral or bacterial
      infection and immune reactions. Therefore, it is expected of culture cells which
      are intended to be re-implanted with autologous serum rather than conventional
      bovine serum. Cell therapy with human mesenchymal stem cells (hMSC),
      differentiating to various cells, is thought to be curative. To culture hMSC with
      human autologous serum (HAS) and re-implant them for cell therapy, we developed a
      completely closed bag system separating serum, comparing proliferation and
      multipotency of hMSC cultured in HAS with those in foetal calf serum (FCS). HAS
      was simply, safely and efficiently obtained with the developed closed bag system.
      Cell proliferation of hMSC cultured in HAS was greater than that in FCS. hMSC,
      exposed to the defined induction medium containing HAS as well as FCS,
      differentiated into osteoblasts and adipocytes. These findings suggest that HAS
      obtained with the developed closed bag system is advantageous in a point of
      decrease in risk of virus or bacterial infection and foreign protein
      contamination and enhancement of proliferation of hMSC.

PMID- 16616868
TI  - A technical tip for creation of a Drapanas mesocaval shunt.

PMID- 16616869
TI  - [Rhabdoid tumours of the central nervous system: five case studies].
AB  - PURPOSE: The rhabdoid cerebral tumors were first identified by Briner et al. in
      1985. Their frequency was estimated to be 2.1% of those affecting children under
      18 months. Such tumors are equally characterized by a critically and speedly
      mortal development. Their historical genesis is still of a controversial issue.
      The aim of the present study was to discuss the various anatomicoclinical and
      therapeutic aspects of these rare tumors. PATIENTS AND METHODS: We report five
      cases diagnosed over a period of eight years (1997-2004) in the Laboratory of
      Anatomy and Pathological Cytology of the University Hospital of Sfax. RESULTS:
      The average age of patients was 20 years old, there were children under 14 years
      and 4 patients were male. Clinical symptomatology showed the predominance of
      intra-cranial hypertension syndrome. Radiography through magnetic resonance
      revealed a heterogeneous tumor process localized respectively on the spine (one
      case), the insula (one case), the temporofrontal lobes (two cases) and the
      medulla (one case). Histological examination of the tumors also showed a
      proliferation of giant cells with a hyaline-based cytoplasmic inclusion. These
      inclusions were positive for vimentin and keratin. An adjuvant radiotherapy
      treatment was prescribed for two patients. A recurrence of rhabdoid tumors
      occurred in two cases. All five patients died within eighteen months. CONCLUSION:
      The cerebral rhabdoid malignant tumor constitutes one of the most aggressive and
      life-threatening intracranial tumors. The optimal management of such tumors
      remains unknown.

PMID- 16616870
TI  - Respiratory chain supercomplexes in the plant mitochondrial membrane.
AB  - The intricate, heavily folded inner membrane of mitochondria houses the
      respiratory chain complexes. These complexes, together with the ATP synthase
      complex, are responsible for energy production, which is stored as ATP. The
      structure of the individual membrane-bound protein components has been well
      characterized. In particular, the use of Blue-native polyacrylamide gel
      electrophoresis has been instrumental in recent years in providing evidence that
      these components are organized into supercomplexes. Single particle electron
      microscopy studies have enabled a structural characterization of some of the
      mitochondrial supercomplexes. This has provided the opportunity to define a
      functional role for these supercomplexes for the first time, in particular for
      the dimeric ATP synthase complex, which appears to be responsible for the folding
      of the inner mitochondrial membrane.

PMID- 16616871
TI  - Hairy root research: recent scenario and exciting prospects.
AB  - High stability of the production of secondary metabolites is an interesting
      characteristic of hairy root cultures. For 25 years, hairy roots have been
      investigated as a biological system for the production of valuable compounds from
      medicinal plants. A better understanding of the molecular mechanism of hairy root
      development, which is based on the transfer of Agrobacterium rhizogenes T-DNA
      into the plant genome, has facilitated its increasing use in metabolic
      engineering. Hairy roots can also produce recombinant proteins from transgenic
      roots, and thereby hold immense potential for the pharmaceutical industry. In
      addition, hairy roots offer promise for phytoremediation because of their
      abundant neoplastic root proliferation. Recent progress in the scaling-up of
      hairy root cultures is making this system an attractive tool for industrial
      processes.

PMID- 16616872
TI  - Acyltransferases in plants: a good time to be BAHD.
AB  - Acylation is a common and biochemically significant modification of plant
      secondary metabolites. Plant BAHD acyltransferases constitute a large family of
      acyl CoA-utilizing enzymes whose products include small volatile esters, modified
      anthocyanins, as well as constitutive defense compounds and phytoalexins. The
      catalytic versatility of BAHD enzymes makes it very difficult to make functional
      predictions from primary sequence alone. Recent advances in genome sequencing and
      the availability of the first crystal structure of a BAHD member are, however,
      providing insights into the evolution and function of these acyltransferases
      within the plant kingdom.

PMID- 16616873
TI  - Seeking completeness in bacterial mutant hunts.
AB  - The identification of most or all of the genetic functions that are required for
      a particular biological process could be achieved through phenotypic studies of
      high genome-coverage mutant collections. Technologies for creating such
      collections, in the form of mixed populations or individually arrayed sequence
      defined mutants, are now available for numerous bacterial species. The analysis
      of mixed mutant collections using microarray-based detection procedures appears
      to be particularly effective in identifying functions required for complex
      processes such as virulence. The phenotypic analysis of sequence-defined mutant
      libraries provides a virtually complete identification of nonessential genes
      required for processes for which suitable screens can be devised. Such libraries
      also serve as a source of individual mutants for examining the biological
      relevance of gene associations revealed by transcriptional profiling or homology.

PMID- 16616875
TI  - Ebola virus: unravelling pathogenesis to combat a deadly disease.
AB  - Ebola virus (EBOV) causes severe haemorrhagic fever leading to up to 90%
      lethality. Increasingly frequent outbreaks and the placement of EBOV in the
      category A list of potential biothreat agents have boosted interest in this
      virus. Furthermore, development of new technologies (e.g. reverse genetics
      systems) and extensive studies on Ebola haemorrhagic fever (EHF) in animal models
      have substantially expanded the knowledge on the pathogenic mechanisms that
      underlie this disease. Two major factors in EBOV pathogenesis are the impairment
      of the immune response and vascular dysfunction. Here, we attempt to summarize
      the current knowledge on EBOV pathogenesis focusing on these two factors and on
      recent progress in the development of vaccines and potential therapeutics.

PMID- 16616874
TI  - Membrane binding domains.
AB  - Eukaryotic signaling and trafficking proteins are rich in modular domains that
      bind cell membranes. These binding events are tightly regulated in space and
      time. The structural, biochemical, and biophysical mechanisms for targeting have
      been worked out for many families of membrane binding domains. This review takes
      a comparative view of seven major classes of membrane binding domains, the C1,
      C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of
      specific headgroup interactions, hydrophobic membrane penetration, electrostatic
      surface interactions, and shape complementarity to bind to specific subcellular
      membranes.

PMID- 16616876
TI  - Knowledge about cardiovascular risk factors among obese individuals.
AB  - BACKGROUND: Obesity is an important biological risk factor for cardiovascular
      disease (CVD). AIMS: The main aim of this study was to answer the question
      whether obese individuals differ from individuals with normal weight with regard
      to knowledge about risk factors for CVD. A further aim was to replicate previous
      findings that obese individuals are at higher risk of developing other biological
      risk factors for CVD. METHOD: Normal weights, BMI<25 kg/m(2) (n=385), and obese,
      BMI> or =30 kg/m(2) (n=159), individuals were identified from a screening program
      conducted among 50-year-old inhabitants of the County of Vastmanland, Sweden.
      Participants answered questions regarding their gender, level of education, and
      items relating to knowledge about cardiovascular risk factors. Total cholesterol
      and blood glucose levels, height, weight and blood pressure were measured.
      RESULTS: Obese individuals did not differ significantly from individuals with a
      normal weight regarding knowledge of cardiovascular risk factors when education
      was controlled for. Obesity and low level of education are associated with other
      risk factors for CVD such as high blood pressure and high serum cholesterol.
      CONCLUSION: Obese individuals are at an increased risk of developing other risk
      factors for CVD but are just as knowledgeable about risk factors for CVD as
      normal weighting individuals.

PMID- 16616877
TI  - Dynamic changes of apoptosis-inducing ligands and Th1/Th2 like subpopulations in
      Hantaan virus-induced hemorrhagic fever with renal syndrome.
AB  - The expression of the apoptosis-inducing ligands, TNF-alpha, FasL and TRAIL on
      peripheral blood mononuclear cells (PBMC) and the levels of their soluble form
      (TNF-alpha, sFasL and sTRAIL) in plasma from 40 hemorrhagic fever with renal
      syndrome (HFRS) patients as well as 26 healthy blood donors were determined by
      flow cytometry (FCM) analysis and sandwich ELISA, respectively. The status of
      Th1, Th2, Tc1 and Tc2 subsets in PBMC was evaluated by intracellular cytokine
      staining and FCM. Compared to controls, the expression of membrane bound FasL and
      TRAIL was up-regulated on surface of PBMC isolated from the HFRS patients,
      particularly on CD8+ T lymphocytes. The levels of TNF-alpha, sFasL and sTRAIL in
      plasma from the HFRS patients in the acute phase increase 4.7-fold, 6.0-fold and
      1.8-fold, respectively, over those from the healthy donors. The percentage of
      Th1, Tc1 and Tc2 subsets in PBMC from the patients also increased significantly
      compared with those from healthy donors. These results indicate that dynamic
      changes occurred in both the membrane bound and soluble forms of apoptosis
      inducing ligands (FasL, TRAIL and TNF-alpha) and proportions of Th1 and CTL in
      HFRS patients increased. Both factors may play an important role in the etiology
      of Hantaan virus infection in humans.

PMID- 16616878
TI  - Ultrasonographic study of left ventricular function at rest in a group of highly
      trained black African handball players.
AB  - AIMS: Most of the studies of athlete's heart have been performed on Caucasian and
      yet, evidence suggests that there are racial differences in the response of the
      heart to certain pathological conditions such as hypertension. This study aimed
      to evaluate the morphologic cardiac changes in a group of highly trained
      Cameroonian handball players. METHODS AND RESULTS: We studied cardiac morphology
      and function as assessed by echocardiography at rest in 21 asymptomatic
      international level handball players and 21 age-, sex-, height- and weight
      matched sedentary controls. Echocardiographic variables were compared between
      groups using unpaired t-test. Compared with controls, wall thickness, relative
      wall thickness (h/R), left ventricular (LV) mass, LV end diastolic diameter
      (LVEDD) and left atrial diameter were significantly greater in athletes. None of
      the athlete exhibited a wall thickness above 12 mm. The ejection fraction (EF)
      and the mitral pattern on pulsed wave Doppler did not differ in the two groups.
      CONCLUSIONS: Both LVEDD and wall thickness of elite Cameroonian handball players
      are increased. There is an increased h/R. The LV EF was normal and not
      supranormal, as is sometimes believed. These cardiac changes are consistent with
      cardiac adaptation required in this type of sportsmen who are submitted both in
      endurance and resistance training.

PMID- 16616879
TI  - Molecular epidemiology of human picobirnaviruses among children of a slum
      community in Kolkata, India.
AB  - Picobirnaviruses are a group of unclassified, non-enveloped, small spherical
      viruses, 35-41 nm in diameter without any apparent surface morphology. They have
      characteristic bisegmented double stranded RNA genome of two types namely large
      profile (2.3-2.6 kbp for the larger and 1.5-1.9 kbp for the smaller segment,
      respectively) or small profile (1.75 and 1.55 kbp for segments 1 and 2,
      respectively). Human picobirnaviruses (n=12 positives; 2/56 diarrhoeic children
      and 10/607 non-diarrhoeic children) with large (n=11) or small (n=1) genome
      pattern were observed in faecal specimens of children from a slum community by
      silver stained PAGE gels. Faecal specimen from four asymptomatic cases
      (P597_02_IND, K135_02_IND, A373_03_IND, A356_03_IND) and one diarrhoeic case
      (K135_03_IND) had genogroup I picobirnaviruses (1-CHN-97 like) showing amplicons
      within the 201 bp region, with primers PicoB25-PicoB43, targeting the conserved
      domain of RNA-dependent RNA polymerase (RdRp) gene. It was interesting to note
      that only the PBV strain P597_02_IND from Kolkata with large genome was closely
      related to a reported strain (similarity with 2-GA-91 from USA was 87% at the
      nucleotide level and 90% at the amino acid level). Sequence analysis showed three
      conserved amino acid domains as well as a highly conserved D-S-D motif,
      characteristic of RNA-dependent RNA polymerase gene of bisegmented, double
      stranded RNA viruses. Sequence data of the picobirnavirus A356_03_IND indicated
      strong heterogeneity with all other picobirnavirus strains sequenced till date.
      After nearly a decade a genogroup II picobirnavirus strain (R227_03_IND) was
      isolated from a diarrhoea case in the community, with small genome profile and
      amplified with specific primers PicoB23-PicoB24; but the sequence data showed
      that it was divergent from the hitherto reported prototype strain 4-GA-91 of
      genogroup II human picobirnaviruses.

PMID- 16616880
TI  - Determination of amiodarone and desethylamiodarone in horse plasma and urine by
      high-performance liquid chromatography combined with UV detection and
      electrospray ionization mass spectrometry.
AB  - A rapid method for the quantification of amiodarone and desethylamiodarone in
      animal plasma using high-performance liquid chromatography combined with UV
      detection (HPLC-UV) is presented. The sample preparation includes a simple
      deproteinisation step with acetonitrile. In addition, a sensitive method for the
      quantification of amiodarone and desethylamiodarone in horse plasma and urine
      using high-performance liquid chromatography combined with electrospray
      ionization tandem mass spectrometry (LC-ESI-MS/MS) is described. The sample
      preparation includes a solid-phase extraction (SPE) with a SCX column. Tamoxifen
      is used as an internal standard for both chromatographic methods. Chromatographic
      separation is achieved on an ODS Hypersil column using isocratic elution with
      0.01% diethylamine and acetonitrile as mobile phase for the HPLC-UV method and
      with 0.1% formic acid and acetonitrile as mobile phase for the LC-MS/MS method.
      For the HPLC-UV method, good linearity was observed in the range 0-5 microg ml(
      1), and in the range 0-1 microg ml(-1) for the LC-MS/MS method. The limit of
      quantification (LOQ) was set at 50 and 5 ng ml(-1) for the HPLC-UV method and the
      LC-MS/MS method, respectively. For the UV method, the limit of detection (LOD)
      was 15 and 10 ng ml(-1) for amiodarone and desethylamiodarone, respectively. The
      LODs of the LC-MS/MS method in plasma were much lower, i.e. 0.10 and 0.04 ng ml(
      1) for amiodarone and desethylamiodarone, respectively. The LODs obtained for the
      urine samples were 0.16 and 0.09 ng ml(-1) for amiodarone and desethylamiodarone,
      respectively. The methods were shown to be of use in horses. The rapid HPLC-UV
      method was used for therapeutic drug monitoring after amiodarone treatment, while
      the LC-MS/MS method showed its applicability for single dose pharmacokinetic
      studies.

PMID- 16616881
TI  - Resuscitation of the depressed newborn.
AB  - The resuscitation of babies at birth is different from the resuscitation of all
      other age groups, and knowledge of the relevant physiology and pathophysiology is
      essential. Although the majority of babies will establish normal respiration and
      circulation without help after delivery, those babies who do not establish
      adequate regular normal breathing, or who have a heart rate of less than 100
      beats per minute, require assistance. Despite the limitation of the available
      evidence, an international body of experts has provided guidelines for neonatal
      resuscitation.

PMID- 16616882
TI  - Osteoblast responses to nucleotides increase during differentiation.
AB  - Accumulating evidence suggests that extracellular nucleotides, signaling through
      P2 receptors, play a role in modulating bone cell function. ATP and ADP stimulate
      osteoclastic resorption, while ATP and UTP are powerful inhibitors of bone
      formation by osteoblasts. We investigated changes in the expression of P2
      receptors with cell differentiation in primary osteoblast cultures. Rat calvarial
      osteoblasts, cultured for up to 10 days, were loaded with the intracellular
      Ca(2+)-sensing fluorophore, Fluo-4 AM, and a fluorescence imaging plate reader
      was used to measure responses to nucleotide agonists. Peak responses occurred
      within 20 s and were evoked by ATP or UTP at concentrations as low as 2 microM.
      Osteoblast number doubled between day 4 and 10 of culture, but the peak
      intracellular Ca(2+) response to ATP or UTP increased up to 6-fold over the same
      period, indicating that osteoblast responsiveness to nucleotides increases as
      cell differentiation proceeds. The approximate order of potency for the most
      active nucleotide agonists at day 8 of culture was ATP > UTP and ATPgammaS > ADP
      > UDP, consistent with the expression of functional P2Y(2), P2X(2), P2Y(4),
      P2Y(1) and P2Y(6) receptors. Smaller responses were elicited by 2-MeSATP, Bz-ATP
      and alpha,beta-meATP, additionally suggesting the presence of functional P2X(1),
      P2X(3), P2X(5) and P2X(7) receptors. Expression of mRNA for the ATP- and UTP
      selective P2Y(2) receptor increased strongly between day 6 and 15 in primary rat
      osteoblasts, whereas mRNAs for the P2Y(4) (also ATP/UTP selective) and P2Y(6)
      (UDP/UTP selective) receptors were highly expressed at intermediate time points.
      In contrast, mRNA for the cell-proliferation-associated P2X(5) receptor decreased
      to undetectable as osteoblasts matured, but mRNA for the cell-death-associated
      P2X(7) receptor was detected at all time points. Similar trends were evident
      using immunostaining and Western blotting for P2 receptors. Exposure to 10 muM
      ATP or UTP during days 10-14 of culture was sufficient to cause near-total
      blockade of the 'trabecular' bone nodules formed by osteoblasts; however, UDP and
      ADP were without effect. Our results show that there is a shift from P2X to P2Y
      expression during differentiation in culture, with mature osteoblasts
      preferentially expressing the P2Y(2) receptor and to a lesser extent P2Y(4) and
      P2Y(6) receptors. Taken together, these data suggest that the P2Y(2) receptor,
      and possibly the P2Y(4) receptor, could function as 'off-switches' for
      mineralized bone formation.

PMID- 16616883
TI  - The effects of container size, frequency and extended horizontal reach on maximum
      acceptable weights of lifting for female industrial workers.
AB  - In the development of our present manual materials handling (MMH) guidelines
      (Snook, S.H., Ciriello, V.M., 1991. The design of manual tasks: revised tables of
      maximum acceptable weights and forces. Ergonomics 34, 1197-1213), the assumption
      was made that the effects of frequency on maximum acceptable weights (MAWs) of
      lifting with a large box (hand distance, 38 cm from chest) were similar to that
      of lifting with a small box (hand distance, 17 cm from chest). The first purpose
      of the present experiment was to investigate this assumption with female
      industrial workers. The second purpose was to study the effects of extended
      horizontal reach lifting (hand distance, 44.6 cm from chest) on MAWs as a
      confirmation of the results of a previous studies on this variable with males
      (Ciriello, V.M., Snook, S.H., Hughes, G.J., 1993. Further studies of
      psychophysically determined maximum acceptable weights and forces. Hum. Factors
      35(1), 175-186; Ciriello, V.M., 2003. The effects of box size, frequency, and
      extended horizontal reach on maximum acceptable weights of lifting. Int. J. Ind.
      Ergon. 32, 115-120). Lastly, we studied the effects of high frequency (20
      lifts/min) on MAWs of lifting. Ten female industrial workers performed 15
      variations of lifting using our psychophysical methodology whereby the subjects
      were asked to select a workload they could sustain for 8h without "straining
      themselves or without becoming unusually tired weakened, overheated or out of
      breath". The results confirmed that MAWs of lifting with the large box was
      significantly effected by frequency. The frequency factor pattern in this study
      was similar to the frequency pattern from a previous study using the small box
      (Ciriello, V.M., Snook, S.H., 1983. A study of size distance height, and
      frequency effects on manual handling tasks. Hum. Factors 25(5), 473-483) for all
      fast frequencies down to one lift every 2 min with deviations of 7%, 15%, and 13%
      for the one lift every 5 and 30 min tasks and the one lift in 8h task,
      respectively. The effects of lifting with an extended horizontal reach decreased
      MAW 22% and 18% for the mid and center lift and the effects of the 20 lifts/min
      frequency resulted in a MAW that was 47% of a 1 lift/min MAW. Incorporating these
      results in future guidelines should improve the design of MMH tasks for female
      workers.

PMID- 16616884
TI  - Rest break interventions in stoop labor tasks.
AB  - Hand cultivation and harvest of agricultural products constitute strenuous
      physical tasks. Working with labor-management ergonomics committees in
      agricultural settings, the UC Agricultural Ergonomics Research Center (AERC)
      tested an experimental rest and recovery protocol for its impact on symptoms and
      productivity during two types of work tasks. The experimental condition consisted
      of adding a 5 min rest break to every working hour in which there was no other
      scheduled break (e.g., lunchtime). This resulted in an additional 20 min of rest
      per workday. We tested the intervention in two trials: Trial one compared workers
      (n=66) randomly assigned to an experimental or a control group during the harvest
      of commercial strawberries. Trial two utilized a cross-over design (n=16 pairs of
      workers) to compare experimental and control conditions while workers inserted
      bud grafts into young 18'' high citrus trees. For both trials, workers under the
      experimental condition reported significantly less severe symptoms than workers
      under control conditions. The order in which the intervention was given, however,
      appeared to result in variations in productivity. We conclude that the
      introduction of frequent, brief rest breaks may improve symptoms for workers
      engaged in strenuous work tasks.

PMID- 16616885
TI  - Carboxyl-terminal hydrophilic tail of a NhaP type Na+/H+ antiporter from
      cyanobacteria is involved in the apparent affinity for Na+ and pH sensitivity.
AB  - Little information is available on the C-terminal hydrophilic tails of
      prokaryotic Na(+)/H(+) antiporters. To address functional properties of the C
      terminal tail, truncation mutants in this domain were constructed. Truncation of
      C-terminal amino acid residues of NhaP1 type antiporter from Synechocystis
      PCC6803 (SynNhaP1) did not change the V(max) values, but increased the K(m)
      values for Na(+) and Li(+) about 3 to 15-fold. Truncation of C-terminal tail of a
      halotolerant cyanobacterium Aphanothece halophytica (ApNhaP1) significantly
      decreased the V(max) although it did not alter the K(m) values for Na(+). The C
      terminal part of SynNhaP1 was expressed in E. coli and purified as a 16kDa
      soluble protein. Addition of purified polypeptide to the membrane vesicles
      expressing the C-terminal truncated SynNhaP1 increased the exchange activities.
      Change of Glu519 and Glu521 to Lys in C-terminal tail altered the pH dependence
      of Na(+)/H(+) and Li(+)/H(+) exchange activities. These results indicate that the
      specific acidic amino acid residues at C-terminal domain play important roles for
      the K(m) and the pH dependence of the exchange activity.

PMID- 16616886
TI  - Classification of muscle spindle afferents innervating the masseter muscle in
      rats.
AB  - Taylor et al. [Taylor, A., Durbaba, R., Rodgers, J.F., 1992a. The classification
      of afferents from muscle spindles of the jaw-closing muscles of the cat. J
      Physiol 456, 609-628] developed a method to classify muscle spindle afferents
      using succinylcholine (Sch) and ramp and hold stretches. They demonstrated that
      cat jaw muscle spindle afferents show high proportion of intermediate responses
      to ramp and hold jaw stretch. Together with observations on the responses to Sch
      their data suggests that the majority of jaw muscle spindle afferents are
      influenced by a combination of nuclear bag(2) and nuclear chain fibres.
      Relatively few are influenced solely by nuclear bag(1) fibres. The purpose of
      this study was to categorize jaw muscle spindle afferent in rodents in response
      to ramp and hold stretches. Several measures were used to classify spindle
      afferents including (1) conduction velocity, (2) coefficient of variation (C.V.)
      of the interspike interval during jaw opening, and (3) the dynamic sensitivity
      and the initial discharge of spindle afferents before and after succinylcholine
      infusion (Sch, 100mg/kg, i.v.). Consistent with observations in the cat jaw
      muscles, the distribution of the conduction velocity and the C.V. of Vmes
      masseter afferents were unimodal. Therefore, these parameters were of little
      value in functional classification of spindle innervation. Succinylcholine
      injection either markedly increased the dynamic sensitivity or produced no change
      in Vmes afferents. Unlike cat jaw muscle spindle afferents, the effect of Sch on
      the initial discharge was not clearly separable from those responding or not
      responding to Sch. These results suggest that rat jaw muscle spindle afferents,
      have physiological properties that are primarily intermediate in nature and are
      likely to reflect a predominance of influence from nuclear bag(2) and chain
      fibres. However, the distinction between bag(2) and chain fibres influences is
      not as clearly defined in the rat compared to the cat.

PMID- 16616887
TI  - Physiological properties of molar-mechanosensitive periodontal neurons in the
      trigeminal ganglion of the rat.
AB  - Spike discharges from periodontal mechanosensitive neurones responding to the
      mechanical stimulation of molar teeth were recorded from the trigeminal ganglion
      of rats anaesthetized with pentobarbital sodium. Maxillary molar-sensitive units
      were close together in a narrow, lateral area of the maxillary division of the
      ganglion, whereas those of mandibular molar-sensitive units were scattered
      throughout the mandibular division. The majority of maxillary molar-sensitive
      units responded only to stimulation of the first molar. They were slowly adapting
      and responded most strongly to pressure applied to the lingual surface and buccal
      cusp of the tooth or to the buccal surface and lingual cusp. By contrast,
      approximately one-half of the mandibular molar-sensitive units were rapidly
      adapting, multitooth units that responded to tooth stimulation almost equally in
      all directions. The other half were slowly adapting and activated most
      effectively by pressure applied to the lingual surface and buccal cusp of the
      molar tooth. These slowly adapting units consisted of first molar-sensitive,
      single- and multitooth units. Differences in the response characteristics of the
      maxillary and mandibular molar-sensitive periodontal units may reflect
      differences in the sensory role of individual molars.

PMID- 16616888
TI  - Influence of N-acylation of a peptide derived from human lactoferricin on
      membrane selectivity.
AB  - Increasing numbers of bacterial strains being resistant to conventional
      antibiotics emphasize the urgent need for new antimicrobial agents. One strategy
      is based on host defence peptides that can be found in every organism including
      humans. We have studied the antimicrobial peptide LF11, derived from the pepsin
      cleavage product of human lactoferrin, known for its antimicrobial and lipid A
      binding activity, and peptide C12LF11, the N-lauryl-derivative of LF11, which has
      owing to the attached hydrocarbon chain an additional hydrophobic segment. The
      influence of this hydrocarbon chain on membrane selectivity was studied using
      model membranes composed of dipalmitoylphosphatidylglycerol (DPPG), mimicking
      bacterial plasma membranes, and of dipalmitoylphosphatidylcholine (DPPC), a model
      system for mammalian membranes. A variety of biophysical techniques was applied.
      Thereby, we found that LF11 did not affect DPPC bilayers and showed only moderate
      effects on DPPG membranes in accordance with its non-hemolytic and weak
      antimicrobial activity. In contrast, the introduction of the N-lauryl group
      caused significant changes in the phase behaviour and lipid chain packing in both
      model membrane systems. These findings correlate with the in vitro tests on
      methicillin resistant S. aureus, E. coli, P. aeruginosa and human red blood
      cells, showing increased biological activity of C12LF11 towards these test
      organisms. This provides evidence that both electrostatic and hydrophobic
      interactions are crucial for biological activity of antimicrobial peptides,
      whereas a certain balance between the two components has to be kept, in order not
      to loose the specificity for bacterial membranes.

PMID- 16616889
TI  - Peptide antibiotics in action: investigation of polypeptide chains in insoluble
      environments by rotational-echo double resonance.
AB  - Rotational-echo double resonance (REDOR) is a solid-state NMR technique that has
      the capability of providing intra- and intermolecular distance and orientational
      restraints in non-crystallizable, poorly soluble heterogeneous molecular systems
      such as cell membranes and cell walls. In this review, we will present two
      applications of REDOR: the investigation of a magainin-related antimicrobial
      peptide in lipid bilayers and the study of a vancomycin-like glycopeptide in the
      cell walls of Staphylococcus aureus.

PMID- 16616890
TI  - Conducting extinction in multiple contexts does not necessarily attenuate the
      renewal of shock expectancy in a fear-conditioning procedure with humans.
AB  - The renewal of Pavlovian-conditioned responses may provide a model for the
      relapse of fear following extinction-based treatments for anxiety disorders.
      Renewal can be observed if conditional stimulus (CS) and unconditional stimulus
      (US) pairings are given in one context, extinction trials of CS presentations in
      a second context, prior to test trials of CS presentations in the original
      acquisition context (ABA renewal). We examined ABA renewal in humans by using a
      fear-conditioning procedure with an unpleasant shock US. A renewal of rated shock
      expectancy was demonstrated with this procedure. Conducting extinction treatment
      in multiple contexts was expected to attenuate the renewal effect. However, the
      renewal of shock expectancy persisted when extinction treatment was given across
      three or five different contexts. With the current renewal design, learning task,
      and measure of conditioned behaviour, extinction treatment does not appear to
      readily generalise to the test context. The use of multiple extinction treatments
      in a clinical setting may not necessarily reduce the likelihood of relapse via a
      renewal effect.

PMID- 16616891
TI  - A dominant negative form of p63 inhibits apoptosis in a p53-independent manner.
AB  - Stem cells are a source of differentiated cells in multiple tissues. If genetic
      alterations occur in stem cells, the problem persists and malignant cancers may
      arise. DeltaNp63alpha-a homologue of the tumor suppressor p53-is exclusively
      expressed in proliferating undifferentiated epithelial cells and cancer cells of
      epidermal origin. Here, we show that DeltaNp63alpha antagonizes DNA damage
      induced apoptosis in a p53-independent manner. We found that upon cellular
      injury, DeltaNp63alpha must be downregulated before apoptotic program can be
      activated. The 5637 cell line has abundant levels of DeltaNp63alpha and mutant
      p53, and it is resistant to DNA damage-induced apoptosis. The knockdown of
      DeltaNp63alpha by RNA interference sensitized these cells to apoptosis upon
      genotoxic insult. This suggests that DeltaNp63alpha plays an anti-apoptotic role
      regardless of the p53 status. Considering the frequent mutations of p53 in tumor
      cells, our results provide important implications for the treatment of cancers in
      which p63 is amplified.

PMID- 16616892
TI  - Cellular senescence, cancer, and organismal aging: a paradigm shift.
AB  - Cellular senescence is an anti-cancer mechanism and may contribute to organismal
      aging. A change in paradigm has been proposed that cellular senescence may reduce
      cancer mortality rather than promote it late in life, and thus positively
      contributes to longevity in organisms with renewable tissues as a common
      mechanism across the species.

PMID- 16616893
TI  - The thrombin binding aptamer GGTTGGTGTGGTTGG forms a bimolecular guanine
      tetraplex.
AB  - In the literature, the thrombin binding aptamer GGTTGGTGTGGTTGG is generally
      taken as a prototype of an intramolecular guanine tetraplex of DNA. Our results,
      however, show that this notion is not true in aqueous solutions. This conclusion
      is based on a dependence of the CD spectra on aptamer concentration, migration of
      the aptamer in polyacrylamide gels, and the Ferguson analysis of the gel
      migration data. The presented data document that the aptamer forms a bimolecular
      tetraplex. We furthermore show that only an extension of the aptamer by a
      sequence containing further guanines, or an elongation of loop regions, causes
      that its tetraplex folding is intramolecular.

PMID- 16616894
TI  - Differential lineage-specific regulation of murine CD45 transcription by Oct-1
      and PU.1.
AB  - Although it has been established that CD45 expression is regulated at the
      transcriptional level, neither the regulatory elements that are responsible for
      its unique expression pattern nor the relevance of its three distinct
      transcriptional start sites (P1a, P1b, and P2) has been fully characterized. We
      studied the contribution of the three start sites to CD45 mRNA production in
      haematopoietic cell lines and primary haematopoietic cells. In myeloid and
      lymphoid cells and cell lines most CD45 transcripts originate from P1b with the
      exception of the thymoma-derived T cell line EL4, in which approximately 90% of
      CD45 transcripts originate from P1a. The degree of contribution of P1a is highest
      in lymphoid cells and increases in T cells following mitogen stimulation. In
      vitro evaluation of sequence upstream of the start sites shows that the P2 start
      site is sufficient for CD45 expression in lymphoid but not in myeloid cells,
      confirms the presence of a PU.1-binding site essential for myeloid expression of
      CD45, and reveals an Octamer-binding site that interacts with both Oct-1 and Oct
      2 and activates CD45 transcription in lymphoid and myeloid cells. These findings
      are the first evidence that Octamer-binding factors are involved in the control
      of CD45 expression.

PMID- 16616895
TI  - Several glutathione S-transferase isozymes that protect against oxidative injury
      are expressed in human liver mitochondria.
AB  - The mitochondrial environment is rich in reactive oxygen species (ROS) that may
      ultimately peroxidize membrane proteins and generate unsaturated aldehydes such
      as 4-hydroxy-2-nonenal (4HNE). We had previously demonstrated the presence of
      hGSTA4-4, an efficient catalyst of 4HNE detoxification, in human liver
      mitochondria to the exclusion of the cytosol. In the present study, GSH-affinity
      chromatography was used in conjunction with biochemical and proteomic analysis to
      determine the presence of additional cytosolic glutathione S-transferases (GSTs)
      in human hepatic mitochondria. HPLC-subunit analysis of GSH affinity-purified
      liver mitochondrial proteins indicated the presence of several potential
      mitochondrial GST isoforms. Electrospray ionization-mass spectrometry analysis of
      eluted mitochondrial GST subunits yielded molecular masses similar to those of
      hGSTP1, hGSTA1 and hGSTA2. Octagonal matrix-assisted laser desorption/ionization
      time of flight mass spectrometry and proteomics analysis using MS-FIT confirmed
      the presence of these three GST subunits in mitochondria, and HPLC analysis
      indicated that the relative contents of the mitochondrial GST subunits were
      hGSTA1>hGSTA2>hGSTP1. The mitochondrial localization of the alpha and pi class
      GST subunits was consistent with immunoblotting analysis of purified
      mitochondrial GST. Enzymatic studies using GSH-purified mitochondrial GST
      fractions demonstrated the presence of significant GST activity using the
      nonspecific GST substrate 1-chloro-2,4-dinitrobenzene (CDNB), as well as 4HNE,
      delta(5)-androstene-3,17-dione (ADI), and cumene hydroperoxide (CuOOH).
      Interestingly, the specific mitochondrial GST activities toward 4HNE, a highly
      toxic alpha,beta-unsaturated aldehyde produced during the breakdown of membrane
      lipids, exceeded that observed in liver cytosol. These observations are
      suggestive of a role of GST in protecting against mitochondrial injury during the
      secondary phase of oxidative stress, or modulation of 4HNE-mediated mitochondrial
      signaling pathways. However, other properties of mitochondrial GST, such as
      conjugation of environmental chemicals and binding of lipophilic non-substrate
      xenobiotics and endogenous compounds, remain to be investigated.

PMID- 16616896
TI  - Critical appraisal of DNA microarrays in psychiatric genomics.
AB  - Transcriptome profiling using DNA microarrays are data-driven approaches with the
      potential to uncover unanticipated relationships between gene expression
      alterations and psychiatric disorders. Studies to date have yielded both
      convergent and divergent findings. Differences may be explained, at least in
      part, by the use of a variety of microarray platforms and analytical approaches.
      Consistent findings across studies suggest, however, that important relationships
      may exist between altered gene expression and genetic susceptibility to
      psychiatric disorders. For example, GAD67, RGS4, DTNBP1, NRG1, and GABRAB2 show
      expression alterations in the postmortem brain of subjects with schizophrenia,
      and these genes have been also implicated as putative, heritable schizophrenia
      susceptibility genes. Thus, we propose that for some genes, altered expression in
      the postmortem human brain may have a dual origin: polymorphisms in the candidate
      genes themselves or upstream genetic-environmental factors that converge to alter
      their expression level. We hypothesize that certain gene products, which function
      as "molecular hubs," commonly show altered expression in psychiatric disorders
      and confer genetic susceptibility for one or more diseases. Microarray gene
      expression studies are ideally suited to reveal these putative disease-associated
      molecular hubs and to identify promising candidates for genetic association
      studies.

PMID- 16616897
TI  - Nuclear targeting of the CaMKII anchoring protein alphaKAP is regulated by
      alternative splicing and protein kinases.
AB  - alphaKAP is an anchoring protein for the Ca(2+)/calmodulin-dependent protein
      kinase II (CaMKII) and is encoded within the same gene as the CaMKIIalpha
      isoform. alphaKAP co-assembles with CaMKII and targets such heteromers to the
      membrane of the sarcoplasmic reticulum, where CaMKII can regulate Ca(2+)
      homeostasis. CaMKII has also nuclear functions in skeletal muscle, however, the
      nuclear targeting mechanism has been elusive. We show here that developmentally
      regulated splicing of exon Ealpha(B) generates a functional nuclear localization
      signal (NLS) in alphaKAP(B), the dominant alphaKAP variant in mature muscle. The
      alphaKAP(A) variant lacks the NLS and dominates in developing muscle before and
      around birth. Both alphaKAP variants localize to membranes, but a small fraction
      of alphaKAP(B) is additionally found in the nucleus. Indeed, alpha-karyopherins
      that mediate nuclear import bound to alphaKAP(B) but not alphaKAP(A) in vitro.
      When the N-terminal membrane anchor of alphaKAP was deleted, localization of
      alphaKAP(B) but not alphaKAP(A) became predominantly nuclear. Co-expression of
      constitutively active CaMKI and IV, which do not bind to alphaKAP, interfered
      with nuclear localization of alphaKAP(B). CaMKIIalpha was found essentially
      exclusively in the cytoplasm when expressed in cell lines but was targeted to the
      nucleus when co-expressed with the nuclear form of alphaKAP(B). Thus, nuclear
      targeting of cytoplasmic CaMKII isoforms by alphaKAP may be regulated by
      developmentally controlled alternative splicing and by protein kinases.

PMID- 16616898
TI  - De novo asymmetric syntheses of C-4-substituted sugars via an iterative
      dihydroxylation strategy.
AB  - A short and highly efficient route to various C-4 substituted sugar lactones has
      been developed. The key to the overall transformation is the sequential osmium
      catalyzed dihydroxylation reaction of substituted 2,4-dienoates and an allylic
      substitution at the C-4 position. When the Sharpless AD-mix procedure is used in
      a matched sense for the second dihydroxylation reaction, it results in an
      exceedingly diastereo- and enantioselective synthesis of several C-4-substituted
      sugars.

PMID- 16616899
TI  - Highly functionalized glyco-conjugated hexahydroazepindiones from saccharide
      imides via the Norrish type II reaction.
AB  - Starting from readily available protected 6-tosylates of D-glucose and D-mannose
      in both their pyranoside and furanoside forms as well as 6-tosylates of alpha-D
      galactopyranose, the corresponding primary succinimido derivatives were obtained
      in good yield by nucleophilic displacement with potassium succinimide. These
      imido sugars were photochemically transformed into hexahydroazepindione
      derivatives such as by means of a Norrish type II reaction. As expected, the
      intramolecular alkylation proceeded via an 1,6 H-abstraction leading to a
      stabilized diradical. The regiochemistry of the photoreaction was controlled by
      configurational, conformational and electronic features and was sometimes
      influenced by the protecting groups. Using this route, a facile approach to a
      novel class of highly functionalized sugar derived heterocycles was developed.

PMID- 16616900
TI  - 2'-Carboxybenzyl glycosides: glycosyl donors for C-glycosylation and conversion
      into other glycosyl donors.
AB  - Glycosylation of various glycosyl acceptors with 2'-carboxybenzyl (CB) 2,3,4,6
      tetra-O-benzyl-beta-D-glucopyranoside and CB 2,3,4,6-tetra-O-benzyl-alpha-D
      mannopyranoside as glycosyl donors afforded alpha-C-glycosides exclusively or
      predominantly in good yields. CB glycosides were also converted to other well
      known glycosyl donors, the corresponding phenyl thioglycoside and the glycosyl
      fluoride derivatives.

PMID- 16616901
TI  - Synthesis of a galacto-configured C-ketoside-based gamma-sugar-amino acid and its
      use in peptide coupling reactions.
AB  - Gamma-sugar-amino acid analogues in the form of C-ketosides can be prepared in 5
      6 steps starting from D-galactono-1,5-lactone. The key step in the synthesis is
      the trimethylsilyl trifluoromethanesulfonate (TMSOTf) promoted C-glycosylation of
      2-deoxy-3-ulopyranosonates with trimethylsilyl cyanide. Hydrogenation of the
      resulting beta-cyano esters provides C-ketoside-based gamma-sugar-amino acids
      that serve as building blocks for the synthesis of unnatural neoglycopeptides.

PMID- 16616902
TI  - Synthesis of n-octyl 2,6-dideoxy-alpha-L-lyxo-hexopyranosyl-(1-->2)-3-amino-3
      deoxy-beta-D-galactopyranoside, an analog of the H-disaccharide antigen.
AB  - The synthesis of an analog of the H-disaccharide antigen (2), in which the
      galactopyranosyl moiety bears an amino group at C-3 and the fucopyranosyl residue
      is deoxygenated at C-2, is reported. The key reaction in the preparation of 2 was
      the glycosylation of an appropriately protected n-octyl 3-azido-3-deoxy
      galactopyranoside derivative with a 2,6-dideoxy thioglycoside promoted by 1
      (phenylsulfinyl)piperidine and triflic anhydride. Disaccharide 2 is of interest
      in studies directed towards understanding the molecular basis of substrate
      recognition by the blood group A and B glycosyltransferases.

PMID- 16616903
TI  - Synthesis of monodeoxy analogues of the trisaccharide alpha-D-Glcp-(1-->3)-alpha
      D-Manp-(1-->2)-alpha-D-ManpOMe recognised by Calreticulin/Calnexin.
AB  - Six (3,4,4',6',3'' or 6'')-monodeoxy analogues of the title trisaccharide (1-6)
      have been prepared utilising monodeoxy monosaccharide precursors. The reducing
      end deoxy derivatives were synthesised by N-iodosuccinimide/silver
      trifluoromethanesulfonate (NIS/AgOTf)-promoted couplings of a common disaccharide
      thioglycoside donor 10 to suitably protected monodeoxy acceptors 9 and 12,
      affording trisaccharides, which after deprotection yielded target structures 1
      and 2. The non-reducing end deoxy derivatives could similarly be produced by
      halide-assisted glycosylations of a common disaccharide acceptor 17 with
      monodeoxy glycosyl bromide donors (obtained from thioglycosides 18 and 20) to
      yield, after removal of protecting groups, target trisaccharides 3 and 4. The
      analogues with the deoxy function in the middle mannose residue, were obtained
      through orthogonal halide-assisted coupling of tetrabenzyl-glucopyranosyl bromide
      to monodeoxy thioglycoside acceptors to give thioglycoside disaccharides, which
      subsequently were used as donors in NIS/AgOTf-promoted couplings to a common 2
      hydroxy-mannose acceptor 15 to afford trisaccharides; deprotection yielded the
      final target compounds 5 and 6.

PMID- 16616904
TI  - A stereoselective 1,2-cis glycosylation toward the synthesis of a novel N-linked
      glycan from the Gram-negative bacterium, Campylobacter jejuni.
AB  - It has been shown that certain prokaryotes, such as Campylobacter jejuni, have
      asparagine (Asn)-linked glycoproteins. However, the structures of their glycans
      are distinct from those of eukaryotic origin. They consist of a bacillosamine
      residue linked to Asn, an alpha-(1-->4)-GalpNAc repeat, and a branching beta-Glcp
      residue. In this paper, we describe a strategy for the stereoselective
      construction of the alpha-(1-->4)-GalpNAc repeat of a C. jejuni N-glycan,
      utilizing a pentafluoropropionyl (PFP) group as a temporary protective group of
      the C-4 OH group of the GalpN donor. The strategy was applied to the synthesis of
      the hexasaccharide alpha-GalpNAc-(1-->4)-alpha-GalpNAc-(1-->4)-[beta-Glcp-(1-
      >3)]-alpha-GalpNAc(1-->4)-alpha-GalpNAc-(1-->4)-GalpNAc.

PMID- 16616905
TI  - Fine tuning of beta-glucosidase inhibitory activity in the 2,5-dideoxy-2,5-imino
      D-mannitol (DMDP) system.
AB  - Based on our extensive studies of D-glucosidase inhibiting 2,5-dideoxy-2,5-imino
      D-mannitol derivatives, we have been trying to create a series of fluorescent
      derivatives with a view to an 'inhibitory activity ruler' based on competitive
      displacement reactions of non-fluorescent inhibitors by fluorescent ones and vice
      versa, which can be performed and followed in microtiter plates or on-chips.
      Thus, a set of compounds was assembled with Ki values between 2 nM and 1 microM
      against Agrobacterium sp. beta-glucosidase.

PMID- 16616907
TI  - Metabolism of 1,3-butadiene to toxicologically relevant metabolites in single
      exposed mice and rats.
AB  - 1,3-Butadiene (BD) was carcinogenic in rodents. This effect is related to
      reactive metabolites such as 1,2-epoxy-3-butene (EB) and especially 1,2:3,4
      diepoxybutane (DEB). A third mutagenic epoxide, 3,4-epoxy-1,2-butanediol (EBD),
      can be formed from DEB and from 3-butene-1,2-diol (B-diol), the hydrolysis
      product of EB. In BD exposed rodents, only blood concentrations of EB and DEB
      have been published. Direct determinations of EBD and B-diol in blood are
      missing. In order to investigate the BD-dependent blood burden by all of these
      metabolites, we exposed male B6C3F1 mice and male Sprague-Dawley rats in closed
      chambers over 6-8h to constant atmospheric BD concentrations. BD and exhaled EB
      were measured in chamber atmospheres during the BD exposures. EB blood
      concentrations were obtained as the product of the atmospheric EB concentration
      at steady state with the EB blood-to-air partition coefficient. B-diol, EBD, and
      DEB were determined in blood collected immediately at the end of BD exposures up
      to 1200 ppm (B-diol, EBD) and 1280 ppm (DEB). Analysis of BD was done by GC/FID,
      of EB, DEB, and B-diol by GC/MS, and of EBD by LC/MS/MS. EB blood concentrations
      increased with BD concentrations amounting to 2.6 micromol/l (rat) and 23.5
      micromol/l (mouse) at 2000 ppm BD and to 4.6 micromol/l in rats exposed to 10000
      ppm BD. DEB (detection limit 0.01 micromol/l) was found only in blood of mice
      rising to 3.2 micromol/l at 1280 ppm BD. B-diol and EBD were quantitatively
      predominant in both species. B-diol increased in both species with the BD
      exposure concentration reaching 60 micromol/l at 1200 ppm BD. EBD reached maximum
      concentrations of 9.5 micromol/l at 150 ppm BD (rat) and of 42 micromol/l at 300
      ppm BD (mouse). At higher BD concentrations EBD blood concentrations decreased
      again. This picture probably results from a competitive inhibition of the EBD
      producing CYP450 by BD, which occurs in both species.

PMID- 16616908
TI  - Stearic acid solubility and cubic phase volume.
AB  - Stearic acid (SA) is highly soluble in structurally diverse solvents. SA/solvent
      packing within a (24.8 A)3 cubic volume explains the stoichiometry of SA
      solubility at multiple temperatures in multiple solvents. In the absence of
      solvent, the cubic volume contains 25 molecules at van der Waals distances from
      each other. At 55 degrees C, SA occupied half the cubic volume in saturated
      solution of four structurally diverse solvents. Below 4% SA/volume (e.g. in
      acetonitrile), the head and foot of each SA molecules on average is more than one
      solvent molecule away from the head and foot of a neighboring SA molecule. At 50%
      SA/cubic volume, -CH2- groups on SA molecules are separated from neighboring -CH2
      groups on SA molecules by a monolayer of solvent molecules. Lowering the
      temperature from 55 to 25 degrees C, the volume fraction of SA decreased by a
      factor of 2 (or more) for every 6 degrees C. Lowering temperature increased the
      relative number of column of solvent molecules in the cubic phase, and
      correspondingly, the distance between SA molecules within the cubic volume
      increased. In three of five solvents, molecular mechanics calculations
      demonstrated the van der Waals stabilization that occurs from SA/SA affinity in
      the absence of solvent is similar in magnitude to the van der Waals stabilization
      from SA/solvent affinity. Methyl-t-butyl ether was less stabilized than hexane,
      acetone or methanol because the more bulky molecules packed less efficiently
      within the cubic volume. The most efficient/most stable packing however was still
      as columns of solvent between columns of SA. The efficiency and stability of SA
      and solvent packing optimal within the (24.8 A)3 cubic volume. Between 100 and 8%
      SA, multiple SA molecules present within the cubic volume function as SA
      aggregates. Both inter- and intra-cubic (phase) volume properties of SA
      aggregates coexist. Although acetonitrile and SA at the molecular level are both
      rod shaped, acetonitrile disrupted the packing of SA molecules within the cubic
      phase. The disrupted packing explains the much lower solubility of SA in
      acetonitrile than in the other solvents. The same molecular structures (e.g.
      methanol) can either stabilize or disrupt the packing of aggregated SA molecules,
      depending upon temperature. The mechanisms of aggregation within cubic volumes
      could also occur with structurally more complicated lipids. Aggregation and
      dispersion from such cubic phases could also be present in more complex chemical
      and/or macromolecular environments.

PMID- 16616906
TI  - Reactive oxygen species signaling in vascular smooth muscle cells.
AB  - Reactive oxygen species (ROS) have been shown to function as important signaling
      molecules in the cardiovascular system. Vascular smooth muscle cells (VSMCs)
      contain several sources of ROS, among which the NADPH oxidases are predominant.
      In VSMCs, ROS mediate many pathophysiological processes, such as growth,
      migration, apoptosis and secretion of inflammatory cytokines, as well as
      physiological processes, such as differentiation, by direct and indirect effects
      at multiple signaling levels. Therefore, it becomes critical to understand the
      different roles ROS play in the physiology and pathophysiology of VSMCs.

PMID- 16616909
TI  - Relationship between adenosine and T-helper 1/T-helper 2 balance in hyperemesis
      gravidarum.
AB  - BACKGROUND: Adenosine modulates the T-helper (Th) 1/T-helper (Th) 2 balance. We
      evaluated the relationship between changes in plasma adenosine and the T-helper
      (Th) 1/T-helper (Th) 2 balance in hyperemesis gravidarum. METHODS: Plasma
      adenosine concentrations and the Th1/Th2 ratio were examined in the peripheral
      blood of 24 women with hyperemesis gravidarum and normal pregnancies. The
      proportion of CD4-positive cells that expressed intracellular cytokines
      (interferon gamma and interleukin 4) was analyzed by flow cytometry. The ratio of
      interferon-gamma-secreting cells to interleukin-4-secreting cells was taken as
      the Th1/Th2 ratio in vivo. The change induced by adenosine-receptor blocker 8
      sulfophenyltheophylline was also measured in vitro to evaluate the possible role
      of adenosine in modifying the Th1/Th2 balance. RESULTS: In hyperemesis
      gravidarum, plasma adenosine and the proportion of interleukin-4-secreting cells
      were increased significantly, and the Th1/Th2 ratio was significantly lower than
      in normal pregnancy (p<0.05). The decrease in the proportion of IL-4-secreting
      cells after adenosine receptor blockade in hyperemesis gravidarum significantly
      exceeded that of normal pregnancy (p<0.05). CONCLUSIONS: Increased plasma
      adenosine may be involved in regulating the Th1/Th2 balance in hyperemesis
      gravidarum.

PMID- 16616910
TI  - No face-like processing for objects-of-expertise in three behavioural tasks.
AB  - In the debate between expertise and domain-specific explanations of "special"
      processing for faces, a common belief is that behavioural studies support the
      expertise hypothesis. The present article refutes this view, via a combination of
      new data and review. We tested dog experts with confirmed good individuation of
      exemplars of their breed-of-expertise. In all experiments, standard results were
      confirmed for faces. However, dog experts showed no face-like processing for dogs
      on three behavioural tasks (inversion; the composite paradigm; and sensitivity to
      contrast reversal). The lack of holistic/configural processing, indicated in the
      first two of these tests, is shown by review to be consistent rather than
      inconsistent with previous studies of objects-of-expertise.

PMID- 16616911
TI  - Algorithm for perturbing thermodynamically infeasible metabolic networks.
AB  - Networks of reactions inside the cell are constrained by the laws of mass and
      energy balance. The second law of thermodynamics further constrains the topology
      of the metabolic network, by disallowing interactions that can sustain themselves
      when they are isolated from the rest of the network. We present an algorithm that
      identifies such subnetworks and makes them feasible by deleting reactions. This
      perturbs the network topology, but preserves the optimality of the mass balance
      solutions. This method has been applied to a full network of Escherichia coli.

PMID- 16616913
TI  - Deadlock, a novel protein of Drosophila, is required for germline maintenance,
      fusome morphogenesis and axial patterning in oogenesis and associates with
      centrosomes in the early embryo.
AB  - The deadlock gene is required for a number of key developmental events in
      Drosophila oogenesis. Females homozygous for mutations in the deadlock gene lay
      few eggs and those exhibit severe patterning defects along both the anterior
      posterior and dorsal-ventral axis. In this study, we analyzed eggs and ovaries
      from deadlock mutants and determined that deadlock is required for germline
      maintenance, stability of mitotic spindles, localization of patterning
      determinants, oocyte growth and fusome biogenesis in males and females. Deadlock
      encodes a novel protein which colocalizes with the oocyte nucleus at midstages of
      oogenesis and with the centrosomes of early embryos. Our genetic and
      immunohistological experiments point to a role for Deadlock in microtubule
      function during oogenesis.

PMID- 16616915
TI  - Persistence of bromadiolone anticoagulant rodenticide in Arvicola terrestris
      populations after field control.
AB  - This paper documents the exposure pattern of a population of small mammals to
      bromadiolone over time in a field-scale follow up. This is the first assessment
      of the field-scale effect of such control operation on the availability of
      bromadiolone-exposed A. terrestris prey to nontarget predator species. It
      indicates that an important risk of poisoning of nontarget species does exist
      during large-scale field control operations with bromadiolone, which is
      contradictory to results obtained from laboratory experiments in the early 1980s
      and consistent with the secondary poisoning hazards due to repeated exposure
      regularly reported during the past 20 years.

PMID- 16616916
TI  - Women's strategies for handling household detergents.
AB  - Performing household-cleaning chores involves the use of chemical detergents;
      these are commonly believed to provide cleaner and safer households. Occupational
      health studies have associated health risks with detergents, including
      respiratory and skin problems. Women are the major users of household detergents,
      as they are in general the primary homemakers. Detergent-handling strategies
      including storage, use, and precautionary measures affect women's exposure to
      chemical detergents and thus affect their health. Studies investigating the
      behavioral component of chemical exposure to detergents at the domestic level are
      scarce. In this study of detergent-handling strategies, women's potential
      exposure was investigated by an ergonomics methodology combining in-depth
      interviews and observations. The participants were 28 women who were responsible
      for cleaning chores in their households. The women lived in Nabaa, a low
      socioeconomic, religiously and ethnically diverse neighborhood on the outskirts
      of Beirut, Lebanon. Information on how women in Nabaa used and perceived
      household detergent, added to the understanding of their potential chemical
      exposure. All the study subjects washed dishes, cleaned bathrooms, and swept
      floors on at least a daily basis. We found that more than half of the
      participants stored different incompatible detergents in close proximity to each
      other. Many of the women stated that they over-consumed detergents. A large
      proportion mixed different detergents together but most of them opened the
      windows while cleaning for ventilation. The majority did not wear gloves and did
      not follow label directions. The participants were consistently exposed to
      chemical detergents and minimal precautionary measures were taken. Cleanliness
      and hygiene had a strong cultural value and were of utmost importance to women
      who prioritized them over excessive exposure to chemicals. The use of an
      ergonomics methodology provided access to important information concerning how
      women make choices that affect their environmental exposure.

PMID- 16616917
TI  - Reinstatement of nicotine-conditioned place preference by drug priming: effects
      of calcium channel antagonists.
AB  - Reinstatement of drug-seeking behaviour in animals is relevant to drug relapse in
      humans. In the present study, we used the conditioned place preference paradigm
      to investigate the establishment, extinction, reinstatement and cross
      reinstatement of nicotine-induced place conditioning in rats. Nicotine produced a
      place preference to the initially less-preferred compartment paired with its
      injections during conditioning (0.5 mg/kg, i.p., three drug sessions). Once
      established, nicotine place preference was extinguished by repeated training.
      Following this extinction phase, the reinstatement of place conditioning was
      investigated. For this purpose, nicotine-experienced rats were challenged with
      nicotine (0.5 mg/kg, i.p.) or morphine (10 mg/kg, i.p.). These priming injections
      of both drugs renewed a marked preference for the compartment previously paired
      with nicotine. In the second step, we examined the influence of the calcium
      channel antagonists, nimodipine (10 and 20 mg/kg, i.p.) and flunarizine (5 and 10
      mg/kg, i.p.), on the reinstatement of nicotine-conditioned place preference
      induced by priming doses of nicotine and morphine. It was shown that the calcium
      channel blockers dose dependently attenuated the reinstatement of nicotine place
      preference induced by both drugs. These findings support the hypothesis that
      similar neural calcium-dependent mechanisms are involved in nicotine- and
      morphine-induced reinstatement. Finally, the conditioned place preference
      paradigm appears to be a useful tool for studies of the relapse of drug-seeking
      behaviour in laboratory animals.

PMID- 16616918
TI  - Cell surface 5T4 antigen is transiently upregulated during early human embryonic
      stem cell differentiation: effect of 5T4 phenotype on neural lineage formation.
AB  - The 5T4 oncofoetal antigen is a cell surface glycoprotein that is transiently
      expressed during mouse ES cell differentiation and correlates with decreased
      pluripotency of such cells. We show that 5T4 antigen is transiently unregulated
      during HES4 and H1 human ES cell differentiation and its expression correlates
      with loss of the pluripotent markers OCT-4 and Tra-1-60 and upregulation of
      transcript markers associated with the three primary germ layers. To confirm that
      absence of cell surface 5T4 antigen represents a pluripotent hES cell phenotype,
      we performed mechanical transfer of either 5T4-ve or 5T4+ve HES4 colonies
      identified using live cell staining. 5T4-ve transfers maintained expression of
      OCT-4 in over 90% of resultant colonies, whereas 5T4+ve transfers exhibited
      significantly lower numbers of OCT-4-expressing colonies (92 +/- 1.4 vs. 2.9 +/-
      2.0%). Interestingly, low cell density 5T4-ve colony transfers exhibited
      increased numbers of OCT-4-expressing colonies compared to large 5T4-ve transfers
      (92 +/- 1.4 vs. 63.2 +/- 1.9%). 5T4-ve and 5T4+ve HES4 and H1 ES cell lines
      expressed markers representative of neuroectoderm lineages, and we assessed the
      formation of neural lineages from these phenotypes in serum-containing medium and
      N2B27 medium. Expression of 5T4 was found to be inversely related to the yield of
      tyrosine-hydroxylase (TH+)-expressing neurons in N2B27 medium, with additional
      mesoderm and endoderm transcript markers detected. Homogeneous glial cell
      populations were derived from low cell density 5T4-ve colony transfers cultured
      in serum-containing medium, with TH+ neuronal formation inhibited in a cell
      density-dependent manner. We conclude that the 5T4 antigen is a transient marker
      of hES cell differentiation and that 5T4 phenotype, colony seeding density and
      culture conditions significantly influence the maintenance of pluripotent hES
      cells and their differentiation to neural lineages.

PMID- 16616919
TI  - The arginine methyltransferase PRMT2 binds RB and regulates E2F function.
AB  - The retinoblastoma gene product (RB) is an important regulator of E2F activity.
      RB recruits a number of proteins, including HDACs, SWI/SNF complex, lysine methyl
      transferase (SUV39H1) and DNA methyltransferase (DNMT1), all of which negatively
      regulate E2F activity with RB. Here, we show that RB interacts with PRMT2, a
      member of the protein arginine methyltransferase family, to regulate E2F
      activity. PRMT2 directly bound and interacted with RB through its AdoMet binding
      domain, in contrast to other PRMT proteins, including PRMT1, PRMT3 and PRMT4. In
      reporter assays, PRMT2 repressed E2F1 transcriptional activity in an RB-dependent
      manner. PRMT2 formed a ternary complex with E2F1 in the presence of RB. To
      further explore the role of endogenous PRMT2 in the regulation of E2F activity,
      the PRMT2 gene was ablated in mice by gene targeting. Compared with PRMT2(+/+)
      mouse embryonic fibroblasts (MEFs), PRMT2(-/-) MEFs demonstrated increased E2F
      activity and early S phase entry following release of serum starvation. Vascular
      injury to PRMT2(-/-) arteries results in a hyperplastic response, consistent with
      increased G1-S phase progression. Taken together, these findings demonstrate a
      novel mechanism for the regulation of E2F activity by a member of the protein
      arginine methyltransferase family.

PMID- 16616920
TI  - Fluoxetine inhibits cortical spreading depression in weaned and adult rats
      suckled under favorable and unfavorable lactation conditions.
AB  - Wistar rats (n = 58) were injected subcutaneously during the lactation period
      with fluoxetine (5, 10, 20 or 40 mg/kg/day) and cortical spreading depression
      (SD) was recorded immediately after weaning (25-30 days of life). An additional
      group (10 mg/kg; n = 8) was SD-recorded at 60-70 days. As compared to the saline
      injected (n = 24) or "ingenuous" (n = 16) controls, fluoxetine dose-dependently
      reduced (P < 0.05) SD-velocities in the young rats by 4, 6, 16 and 15%,
      respectively, and in adult rats by 13%. In another experiment (26 adult rats),
      topical cortical application of fluoxetine (5 and 10 mg/ml solutions over the
      intact dura-mater for 10 min; n = 12 and 14, respectively) dose-dependently
      reduced SD-velocity (7.6% and 43.3% maximal reductions; P < 0.05). SD-propagation
      was blocked in 4 out of the 14 W-rats topically treated with the highest
      fluoxetine concentration (10 mg/ml). This topical fluoxetine effect was reverted
      after flushing the treated region with saline. In additional, 58 early
      malnourished rats, fluoxetine applied during the suckling period (10 mg/kg/day,
      s.c.) and topically (10 mg/ml) also reduced (P < 0.05) SD-velocities by 18 and
      22% for the systemic treatment (young and adult animals, respectively) and by
      22.4% for the topical one. The present fluoxetine action supports the hypothesis
      of an antagonistic serotoninergic influence on SD, as previously suggested in
      experiments using other serotoninergic drugs. Data also suggest that early
      malnutrition does not greatly affect fluoxetine effects on SD.

PMID- 16616921
TI  - Reduction in oxidative stress and cell death explains hypothyroidism induced
      neuroprotection subsequent to ischemia/reperfusion insult.
AB  - Hypometabolic state following hypothermia is known to protect tissues from
      ischemic injury. Hypothyroidism produces a hypometabolic state. The present study
      was undertaken to investigate the protective effects of hypothyroidism following
      cerebral ischemia and to ascertain the underlying mechanism. Euthyroid (E) and
      hypothyroid (H) animals were exposed to a 2 h of middle cerebral artery occlusion
      followed by 24 h of reperfusion (I/R). Specific enzymatic methods and
      flowcytometry were used to assess the quantitative changes of molecules involved
      in neuronal damage as well as in protection. As compared to euthyroid ischemic
      reperfused (E + I/R) rats, H + I/R rats had insignificant neurological deficit,
      and smaller area of infarct. H + I/R rats had significantly lower markers of
      oxidative stress, and lactate dehydrogenase (LDH) activity (a marker for
      necrosis). Natural antioxidant activity (particularly superoxide dismutase) and
      integrity of mitochondria (membrane potential) were maintained in H + I/R group
      but not in E + I/R group. The number of neurons undergoing apoptosis
      significantly lower in hypothyroid ischemic rats as compared to euthyroid ones.
      These results suggest that hypothyroid animals face ischemia and reperfusion much
      better compared to euthyroid animals. A possible explanation could be the
      decreased oxidative stress and maintained antioxidant activity that finally leads
      to a decrease in necrosis and apoptosis. These observations may suggest
      strategies to induce brain-specific downregulation of metabolism that may have
      implications in the management of strokes in human beings.

PMID- 16616922
TI  - Mannose hyperbranched dendritic polymers interact with clustered organization of
      DC-SIGN and inhibit gp120 binding.
AB  - DC-SIGN (dendritic cell-specific ICAM-3 grabbing non-integrin) is a C-type lectin
      receptor of dendritic cells and is involved in the initial steps of numerous
      infectious diseases. Surface plasmon resonance has been used to study the
      affinity of a glycodendritic polymer with 32 mannoses, to DC-SIGN. This
      glycodendrimer binds to DC-SIGN surfaces in the submicromolar range. This binding
      depends on a clustered organization of DC-SIGN mimicking its natural organization
      as microdomain in the dendritic cells plasma membrane. Moreover, this compound
      inhibits DC-SIGN binding to the HIV glycoprotein gp120 with an IC50 in the
      micromolar range and therefore can be considered as a potential antiviral drug.

PMID- 16616923
TI  - Oxidised LDL modulate adipogenesis in 3T3-L1 preadipocytes by affecting the
      balance between cell proliferation and differentiation.
AB  - The effects of oxidised LDL (oxLDL) on cell proliferation, apoptosis and hormone
      induced differentiation have been evaluated for the first time in 3T3-L1
      preadipocytes. Unlike control cells, oxLDL-treated preadipocytes showed a high
      proliferation rate, a low apoptosis level, and an impaired differentiation
      process with an increased preadipocyte factor-1 (Pref-1) mRNA expression at late
      times. By silencing Pref-1 mRNA or inhibiting its expression with an increased
      dexamethasone concentration, differentiation occurred as usual, which
      demonstrates the key role of Pref-1 overexpression. The results suggest a
      specific action of oxLDL on the adipogenesis inhibitor Pref-1, as indicated also
      by its reappearance in mature adipocytes treated with oxLDL. The inhibitory
      effects of oxLDL on differentiation required oxLDL uptake by CD36, and were
      associated with lipoprotein lipids. These results point to oxLDL as a modulator
      of adipose tissue mass and as possible link between obesity and its clinical
      complications.

PMID- 16616924
TI  - Spotlight on... Judit Ovadi. Interview by Tine Walma.

PMID- 16616925
TI  - Laparoscopic management of cervical agenesis.
AB  - OBJECTIVE: To assess the possibility of laparoscopic management of cervical
      agenesis. DESIGN: Case report. SETTING: Patient recruited from a tertiary
      referral hospital. PATIENT(S): Adult female with diagnosis of cervical agenesis.
      INTERVENTION(S): Laparoscopic uterovaginal anastomosis. MAIN OUTCOME MEASURE(S):
      The patency of the anastomosis site was assessed with hysteroscopy. RESULT(S):
      Patient was menstruating normally and had been sexually active at 6 months after
      the procedure. CONCLUSION(S): Laparoscopic treatment of these cases is feasible
      and should be considered as a first-line treatment option.

PMID- 16616926
TI  - Mutual consistency between simulated and measured pressure drops in silica
      monoliths based on geometrical parameters obtained by three-dimensional laser
      scanning confocal microscope observations.
AB  - The geometrical properties of co-continuous macroporous silica monoliths have
      been studied by laser scanning confocal microscopy (LSCM) and a comparison has
      been made with those obtained by conventional mercury intrusion method.
      Tetrahedral skeleton model (TMS), which mimics the gel skeleton shape of
      monoliths, was compared with real monoliths in terms of macropore and porosity
      using the geometrical parameters extracted from the LSCM observations. Liquid
      flow behavior through the macroporous silica monoliths was examined in comparison
      with those simulated using TSM, based on the geometrical properties obtained from
      LSCM observations. Heterogeneity in macropore topology and connectivity in pores
      and skeletons are suggested to contribute to the improvement of the model
      structure for macroporous monoliths.

PMID- 16616927
TI  - Sol-gel molecular imprinted ormosil for solid-phase extraction of
      methylxanthines.
AB  - A organically modified molecularly imprinted silica (MIS), selective for
      methylxanthines, was prepared using a simple sol-gel procedure. Caffeine was used
      as template; 3-aminopropyltrimethoxysilane (APTMS) as functional monomer and
      tetraethyl orthosilicate (TEOS) as reticulating agent. The material was packed on
      solid-phase extraction (SPE) cartridges and evaluated with aqueous test samples,
      natural water and human urine; a quantitative method for methylxanthines in
      water, using SPE cartridges packed with the MIS coupled with HPLC-UV was
      developed. The MIS was highly specific for methylxanthines, with an imprinting
      factor of (20.5+/-1.9). The analytical method resulted in detection limits of 85
      microgL(-1) for theobromine, 44 microgL(-1) for theophylline and 53 microgL(-1)
      for caffeine.

PMID- 16616929
TI  - Iron oxide modified diamond blends containing ultradispersed diamond.
AB  - Iron oxide modified diamond blends containing different amounts of ultradispersed
      diamond were prepared and characterized by nitrogen physisorption, X-ray
      diffraction, temperature programmed reduction, Mossbauer and IR spectroscopy. The
      catalytic behavior of these composite materials in methanol decomposition to
      hydrogen, carbon monoxide, and methane has been also studied. The initial state
      and phase transformations of the supported highly dispersed iron oxide particles
      in various pretreatment media, as well as their reductive and catalytic
      properties, strongly depend on the ultradispersed diamond content in the diamond
      blends.

PMID- 16616928
TI  - Field-amplified sample stacking capillary electrophoresis with
      electrochemiluminescence applied to the determination of illicit drugs on
      banknotes.
AB  - Capillary electrophoresis (CE) with Ru(bpy)3(2+) electrochemiluminescence (ECL)
      detection system was established to the determination of contamination of
      banknotes with controlled drugs and a high efficiency on-column field-amplified
      sample stacking (FASS) technique was also optimized to increase the ECL
      intensity. The method was illustrated using heroin and cocaine, which are two
      typical and popular illicit drugs. Highest sample stacking was obtained when 0.01
      mM acetic acid was chosen for sample dissolution with electrokinetical injection
      for 6 s at 17 kV. Under the optimized conditions: ECL detection at 1.2 V,
      separation voltage 10.0 kV, 20 mM phosphate-acetate (pH 7.2) as running buffer, 5
      mM Ru(bpy)3(2+) with 50 mM phosphate-acetate (pH 7.2) in the detection cell, the
      standard curves were linear in the range of 7.50x10(-8) to 1.00x10(-5) M for
      heroin and 2.50x10(-7) to 1.00x10(-4) M for cocaine and detection limits of 50 nM
      for heroin and 60 nM for cocaine were achieved (S/N = 3), respectively. Relative
      standard derivations of the ECL intensity and the migration time were 3.50 and
      0.51% for heroin and 4.44 and 0.12% for cocaine, respectively. The developed
      method was successfully applied to the determination of heroin and cocaine on
      illicit drug contaminated banknotes without any damage of the paper currency. A
      baseline resolution for heroin and cocaine was achieved within 6 min.

PMID- 16616930
TI  - Crystal structure of the C-terminal domain of S.cerevisiae eIF5.
AB  - eIF5, a GTPase-activating protein (GAP) specific for eIF2, plays a critical role
      in pre-initiation complex assembly and correct AUG selection during eukaryotic
      translation initiation. eIF5 is involved in the formation of the multifactor
      complex (MFC), an important intermediate of the 43S pre-initiation complex. The C
      terminal domain (CTD) of eIF5 functions as the structural core in the MFC
      assembly. Here we report the 1.5A crystal structure of eIF5-CTD, confirming that
      eIF5-CTD contains an atypical HEAT motif. In addition, analyzing the
      electrostatic potential and the distribution of conserved residues on the protein
      surface, we confirm and suggest some potential regions of interactions between
      eIF5-CTD and other eIFs. The structure of eIF5-CTD provides useful information in
      understanding the mechanism of the MFC assembly.

PMID- 16616931
TI  - Structural basis for the phosphorylation-regulated focal adhesion targeting of
      type Igamma phosphatidylinositol phosphate kinase (PIPKIgamma) by talin.
AB  - Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key lipid messenger that
      regulates myriad diverse cellular signaling pathways. To ensure specificity in
      disparate cellular events, PIP2 must be localized to specific sub-cellular sites.
      At PIP2-regulated focal adhesion (FA) sites, such localization is in part
      mediated via the recruitment and activation of PIP2-producing enzyme, type Igamma
      phosphatidylinositol phosphate kinase (PIPKIgamma), by a phosphotyrosine binding
      (PTB) domain of talin. Transient phosphorylation of PIPKIgamma at Y644 regulates
      the interaction and efficient FA targeting of PIPKIgamma; however, the underlying
      structural basis remains elusive. We have determined the NMR structure of talin-1
      PTB in complex with the Y644-phosphorylated PIPKIgamma fragment (WVpYSPLH). As
      compared to canonical PTB domains that typically recognize the NPXpY turn motif
      from a variety of signaling proteins, our structure displays an unusual non-NPXpY
      based recognition mode for talin-1 PTB where K(357)RW in beta5 strand forms an
      antiparallel beta-sheet with the VpYS of PIPKIgamma. A specific electrostatic
      triad between K357/R358 of talin-1 PTB and the pY644 of PIPKIgamma was observed,
      which is consistent with the mutagenesis and isothermal calorimetry data.
      Combined with previous in vivo data, our results provide a framework for
      understanding how phosphorylation of Y644 in PIPKIgamma promotes its specific
      interaction with talin-1, leading to efficient local synthesis of PIP2 and
      dynamic regulation of integrin-mediated FA assembly.

PMID- 16616932
TI  - Computational sampling of a cryptic drug binding site in a protein receptor:
      explicit solvent molecular dynamics and inhibitor docking to p38 MAP kinase.
AB  - An increasing number of structural studies reveal alternative binding sites in
      protein receptors that become apparent only when an inhibitor binds, and correct
      prediction of these situations presents a significant challenge to computer-aided
      drug design efforts. A striking example is provided by recent crystal structures
      of the p38 MAP kinase, where a 10A movement of the Phe169 side-chain creates a
      new binding site adjacent to the ATP binding site that is exploited by the diaryl
      urea inhibitor BIRB796. Here, we show that this binding site can be successfully
      and repeatedly identified in explicit-solvent molecular dynamics (MD) simulations
      of the protein that begin from an unliganded p38 crystal structure. Ligand
      docking calculations performed on 5000 different structural snapshots generated
      during MD indicate that the conformations sampled are often surprisingly
      competent to bind the inhibitor BIRB796 in the crystallographically correct
      position and with docked energies that are generally more favorable than those of
      other positions. Similar docking studies with an ATP-binding site-directed
      inhibitor suggest that it may be possible to develop hybrid inhibitors that
      target both the ATP and cryptic binding sites simultaneously. Intriguingly, both
      inhibitors are occasionally found to dock correctly even with p38's "DFG" motif
      in the "wrong" conformation and BIRB796 can successfully dock, albeit
      infrequently, without significant displacement of the Phe169 side-chain; this
      suggests that the inhibitor might facilitate the latter's conformational change.
      Finally, two quite different conformations of p38's DFG motif are also sampled
      for extended periods of time during the simulations; these may provide new
      opportunities for inhibitor development. The MD simulations reported here, which
      total 390 ns in length, therefore demonstrate that existing computational methods
      may be of surprising utility in predicting cryptic binding sites in protein
      receptors prior to their experimental discovery.

PMID- 16616933
TI  - Crystal structure of neoculin: insights into its sweetness and taste-modifying
      activity.
AB  - Although the majority of sweet compounds are of low molecular mass, several
      proteins are known to elicit sweet taste responses in humans. The fruit of
      Curculigo latifolia contains a heterodimeric protein, neoculin, which has both
      sweetness and a taste-modifying activity that converts sourness to sweetness.
      Here, we report the crystal structure of neoculin at 2.76A resolution. This is
      the first well-defined tertiary structure of a taste-modifying protein of this
      kind. The overall structure is quite similar to those of monocot mannose-binding
      lectins. However, crucial topological differences are observed in the C-terminal
      regions of both subunits. In both subunits of neoculin, the C-terminal tails turn
      up to form loops fixed by inter-subunit disulfide bonds that are not observed in
      the lectins. Indeed, the corresponding regions of the lectins stretch straight
      over the surface of another subunit. Such a C-terminal structural feature as is
      observed in neoculin results in a decrease in subunit-subunit interactions.
      Moreover, distribution of electrostatic potential on the surface of neoculin is
      unique and significantly different from those of the lectins, particularly in the
      basic subunit (NBS). We have found that there is a large cluster composed of six
      basic residues on the surface of NBS, and speculate that it might be involved in
      the elicitation of sweetness and/or taste-modifying activity of neoculin.
      Molecular dynamics simulation based on the crystallography results suggests that
      neoculin may adopt a widely "open" conformation at acidic pH, while unprotonated
      neoculin at neutral pH is in a "closed" conformation. Based on these simulations
      and the generation of a docking model between neoculin and the sweet-taste
      receptor, T1R2-T1R3, we propose the hypothesis that neoculin is in dynamic
      equilibrium between open and closed states, and that the addition of an acid
      shifts the equilibrium to the open state, allowing ligand-receptor interaction.

PMID- 16616934
TI  - Overexpression of hepatitis C virus NS5A protein induces chromosome instability
      via mitotic cell cycle dysregulation.
AB  - Hepatocellular carcinoma (HCC) is a common primary cancer associated with high
      incidences of genetic variations including chromosome instability. Moreover, it
      has been demonstrated that hepatitis C virus (HCV) is one of the major causes of
      HCC. However, no previous work has assessed whether HCV proteins are associated
      with the induction of chromosome instability. Here, we found that liver cell
      lines constitutively expressing full-length or truncated versions of the HCV
      genome show a high incidence of chromosome instability. In particular, the
      overexpression of HCV NS5A protein in cultured liver cells was found to promote
      chromosome instability and aneuploidy. Further experiments showed that NS5A
      induced chromosome instability is associated with aberrant mitotic regulations,
      such as, an unscheduled delay in mitotic exit and other mitotic impairments (e.g.
      multi-polar spindles). Thus, our results indicate that HCV NS5A protein may be
      directly involved in the induction of chromosome instability via mitotic cell
      cycle dysregulation, and provide novel insights into the molecular mechanisms of
      HCV-associated hepatocarcinogenesis.

PMID- 16616935
TI  - An analysis of intron positions in relation to nucleotides, amino acids, and
      protein secondary structure.
AB  - We present an analysis of intron positions in relation to nucleotides, amino acid
      residues, and protein secondary structure. Previous work has shown that intron
      sites in proteins are not randomly distributed with respect to secondary
      structures. Here we show that this preference can be almost totally explained by
      the nucleotide bias of splice site machinery, and may well not relate to protein
      stability or conformation at all. Each intron phase is preferentially associated
      with its own set of residues: phase 0 introns with lysine, glutamine, and
      glutamic acid before the intron, and valine after; phase 1 introns with glycine,
      alanine, valine, aspartic acid, and glutamic acid; and phase 2 introns with
      arginine, serine, lysine, and tryptophan. These preferences can be explained
      principally on the basis of nucleotide bias at intron locations, which is in
      accordance with previous literature. Although this work does not prove that
      introns are inserted into genomes at specific proto-splice sites, it shows that
      the nucleotide bias surrounding introns, however it originally occurred, explains
      the observed correlations between introns and protein secondary structure.

PMID- 16616936
TI  - P50 sensory gating in panic disorder.
AB  - Previous studies with prepulse inhibition in panic disorder (PD) have suggested
      that the early stages of sensory information processing are abnormal in patients
      with PD. To further investigate sensory gating function in panic disorder we
      performed a case-control study in a sample of 28 patients with PD, compared to 28
      normal subjects and 28 schizophrenic subjects evaluating auditory mid-latency
      evoked potential P50 in a double-click paradigm as a measure of sensory gating.
      PD subjects showed weaker sensory gating as evidenced by higher P50 ratios as
      compared to normal subjects (62.5% vs. 45.4%, p=0.03) and higher S2 (test)
      amplitude (3.5 microV vs. 2.1 microV, p=0.01). Schizophrenic subjects when
      compared to healthy controls showed higher P50 ratios as compared to normal
      subjects (79.2% vs. 45.4%, p<0.01) and higher S2 amplitude (3.3 microV vs. 2.1
      microV, p=0.01), but were not statistically different from PD subjects (p>0.1).
      The present study corroborates recent findings of sensory gating dysfunction in
      PD. Further studies are still necessary to better understand the pathophysiology
      of this neurophysiological dysfunction and its nature as a trait or a state
      marker.

PMID- 16616937
TI  - Signal transducers and activators of transcription 1 and 3 in prostate: effect of
      sexual activity.
AB  - The signal transducers and activators of transcription (Stat) are effector
      molecules downstream of cytokine receptors. Ligand occupancy of these receptors
      results in the tyrosine phosphorylation, dimerization and nuclear translocation
      of the Stat family of transcription factors and by these means regulate gene
      expression. Prolactin receptors as members of the cytokine-hematopoietin receptor
      superfamily, are linked to Stat activation. Sexual stimulation leads to an
      increase in prolactin secretion that might be involved in long-term changes in
      the protein repertoire associated to prostate hyperplasia. In order to gain
      insight into this phenomenon, we analyzed the tyrosine phosphorylation and DNA
      binding activity of two members of the Stat family in the prostate of sexual
      experienced rats after different number of ejaculations. A significant increase
      in Stat-1 and Stat-3 tyrosine phosphorylation was found after three ejaculations.
      Concomitantly an increase in Stat-1 and Stat-3 DNA-binding activity is detected
      after two and three ejaculation series. These results, favor the notion that
      ejaculation-induced prolactin secretion activates its prostate receptors
      resulting in Stat-1 and Stat-3 nuclear translocation, event likely to be
      associated to the so-called benign prostate hyperplasia.

PMID- 16616938
TI  - Effect of pterostilbene on hepatic key enzymes of glucose metabolism in
      streptozotocin- and nicotinamide-induced diabetic rats.
AB  - The purpose of this study was to investigate the effect of pterostilbene and its
      effect on key enzymes of glucose metabolism. Diabetic rats were orally
      administered with pterostilbene (10, 20, 40 mg/kg) for 2, 4 and 6 weeks on
      glucose was determined. Administration of pterostilbene at 40 mg/kg significantly
      decreases plasma glucose. Based on these data, the higher dose, 40 mg/kg
      pterostilbene, was selected for further evaluation. Oral administration of
      pterostilbene for 6 weeks on glucose, insulin levels and hepatic enzymes in
      normal and streptozotocin (STZ)-nicotinamide-induced diabetic rats. A significant
      decrease in glucose and significant increase in plasma insulin levels were
      observed in normal and diabetic rats treated with pterostilbene. Treatment with
      pterostilbene resulted in a significant reduction of glycosylated hemoglobin and
      an increase in total hemoglobin level. The activities of the hepatic enzymes such
      as hexokinase was significantly increased whereas glucose-6-phosphatase, fructose
      1,6-bisphosphatase were significantly decreased by the administration of
      pterostilbene in diabetic rats. A comparison was made between the action of
      pterostilbene and the antidiabetic drug--metformin.

PMID- 16616939
TI  - Gaze but not arrows: a dissociative impairment after right superior temporal
      gyrus damage.
AB  - Superior temporal sulcus (STS) activation has consistently been demonstrated in
      the normal brain when viewing eyes, and thus this area is implicated as a gaze
      processing region in humans. In a recent report, we have presented a case, M.J.,
      with a well-circumscribed lesion to the right superior temporal gyrus (STG), who
      demonstrated impaired discrimination of gaze direction. In the aim to make
      distinct whether this impairment is unique to gaze, we have applied a spatial
      cueing paradigm established by Kingstone and colleagues. In our experiment,
      pictorial gaze and symmetrical arrows were centrally presented as non-predictive,
      spatial cues in detecting peripheral targets. Fifteen normal subjects and M.J.
      participated in the experiment. In concordance with previous reports, controls
      demonstrated a significant facilitation of reaction times in detecting targets
      cued by congruent gaze/arrows, compared with incongruent cues. In striking
      contrast, M.J. showed no such congruency advantage for gaze, in the face of a
      normal congruency advantage for arrows. We have demonstrated that a circumscribed
      lesion to the right STG impairs the ability to utilize biological directional
      information such as gaze, but leaves the non-biological counterpart (arrows)
      intact. This dissociation implies that indeed, the STS specializes in processing
      gaze.

PMID- 16616941
TI  - Neuropsychological sequelae of digital mobile phone exposure in humans.
AB  - The effect of electromagnetic fields from digital mobile phones (DMP) on
      cognitive functioning is an area receiving increased attention. This study
      compares the performance of 120 volunteers on 8 neuropsychological tests during
      real or sham exposure to a DMP set to maximum permissible radiofrequency power
      output. When results were adjusted for known covariates (gender, age, or
      education), several alterations at significance levels of p<0.05 were obtained.
      Of these, simple and choice reaction times (CRT) showed strong evidence of
      impairment. Further, performance on the Trail Making Task (TMT) improved,
      supporting the hypothesis that DMP radiofrequency emissions improve the speed of
      processing of information held in working memory.

PMID- 16616940
TI  - Activity and effective connectivity of parietal and occipital cortical regions
      during haptic shape perception.
AB  - It is now widely accepted that visual cortical areas are active during normal
      tactile perception, but the underlying mechanisms are still not clear. The goal
      of the present study was to use functional magnetic resonance imaging (fMRI) to
      investigate the activity and effective connectivity of parietal and occipital
      cortical areas during haptic shape perception, with a view to potentially
      clarifying the role of top-down and bottom-up inputs into visual areas. Subjects
      underwent fMRI scanning while engaging in discrimination of haptic shape or
      texture, and in separate runs, visual shape or texture. Accuracy did not differ
      significantly between tasks. Haptic shape-selective regions, identified on a
      contrast between the haptic shape and texture conditions in individual subjects,
      were found bilaterally in the postcentral sulcus (PCS), multiple parts of the
      intraparietal sulcus (IPS) and the lateral occipital complex (LOC). The IPS and
      LOC foci tended to be shape-selective in the visual modality as well. Structural
      equation modelling was used to study the effective connectivity among the haptic
      shape-selective regions in the left hemisphere, contralateral to the stimulated
      hand. All possible models were tested for their fit to the correlations among the
      observed time-courses of activity. Two equivalent models emerged as the winners.
      These models, which were quite similar, were characterized by both bottom-up
      paths from the PCS to parts of the IPS, and top-down paths from the LOC and parts
      of the IPS to the PCS. We conclude that interactions between unisensory and
      multisensory cortical areas involve bidirectional information flow.

PMID- 16616942
TI  - The nature of lexico-semantic processing deficits in mild cognitive impairment.
AB  - Lexico-semantic impairments in Alzheimer disease (AD) have been attributed to
      abnormalities in both intentional and automatic access to semantic memory.
      However, the order in which these impairments appear during the course of the
      disease is unclear. We sought to answer this question by documenting lexico
      semantic impairments in 61 subjects with mild cognitive impairment (MCI), a pre
      AD stage, and by comparing them to those of 39 AD and 60 normal elderly (NE)
      subjects. All subjects were tested with intentional access tasks (picture naming
      and semantic probes), automatic access tasks (lexical decision and priming), and
      executive function tasks (Stroop and Stroop-Picture naming). Results indicated
      that the MCI group was only impaired on tasks of intentional access relative to
      the AD group who was impaired on both types of tasks. Because most MCI subjects
      eventually develop AD, these results suggest that intentional access to semantic
      memory is impaired before automatic access. Further, impairments on the Stroop
      Picture naming task but not on the Stroop task, suggest that lexico-semantic
      impairments in the MCI group may be related to inhibition deficits during
      semantic search. Findings are discussed in light of executive dysfunctions within
      the framework of semantic memory theories.

PMID- 16616943
TI  - Interleukin-10 (IL-10) but not Lipopolysaccharide (LPS) produces increased motor
      activity and abnormal exploratory patterns while impairing spatial learning in
      Balb/c mice.
AB  - Lipopolysaccharide (LPS) is a potent endotoxin, which produces "sickness
      behaviours" including loss of weight, loss of interest in food and decreased
      exploration. LPS has also been shown in some studies to cause deficits in various
      learning and memory abilities, while in others these LPS-induced learning
      impairments have been attributed to performance-related deficits rather than
      learning deficits per se. Here, we use the novelty-preference paradigm, a task
      that minimises performance-related factors such as motivation, in an attempt to
      extract and examine the effects of LPS on spatial learning. In addition, some
      studies have indicated that the anti-inflammatory cytokine Interleukin-10 (IL-10)
      can alleviate some of the symptoms induced by LPS. Here, we also examine the
      effect of IL-10 on feeding, motor and learning behaviours. We demonstrate that a
      single injection of LPS does produce a lack of interest in food and weight loss;
      LPS, however, does not impair habituation in the novelty-preference paradigm.
      Furthermore, co-injection of IL-10 with LPS does not attenuate the LPS-induced
      effects of weight loss and lack of food intake. Interestingly, a single injection
      of IL-10 produces abnormal patterns of exploration, a general increase in
      activity and abnormal patterns of habituation.

PMID- 16616944
TI  - Prolonged separation delays wound healing in monogamous California mice,
      Peromyscus californicus, but not in polygynous white-footed mice, P. leucopus.
AB  - Social interactions are often stressful, but under certain circumstances, they
      may be beneficial for health and well-being. In a previous study, wound healing
      was slowed after mate separation (2 days) in monogamous California mice,
      Peromyscus californicus, but not polygynous white-footed mice, P. leucopus.
      Although these results indicate that positive social interaction is critical for
      immune activity in some species, the extent to which such social effects are
      enduring remains unspecified. The goal of the present experiments was to
      determine whether a period representing approximately 20% of expected adult
      lifespan of these species in the wild (8 weeks) would affect wound healing.
      Because our experimental design required that the same animals were wounded
      twice, we were also able to determine the extent to which wound healing is
      repeatable. Wound healing remained delayed after 8 weeks of separation in P.
      californicus, and healing scores were not correlated between first and second
      wounds within individuals. In P. leucopus however, housing conditions did not
      influence wound healing, but first and second wound healings were correlated
      indicating repeatability. In sum, our results suggest that positive social
      interactions may be important for promoting immune activity in some species.

PMID- 16616945
TI  - Activation of peroxisome proliferator-activated receptor-gamma (PPARgamma)
      induces cell death through MAPK-dependent mechanism in osteoblastic cells.
AB  - The present study was undertaken to determine the role of the mitogen-activated
      protein kinase (MAPK) subfamilies in cell death induced by PPARgamma agonists in
      osteoblastic cells. Ciglitazone and troglitazone, PPARgamma agonists, resulted in
      a concentration- and time-dependent cell death, which was largely attributed to
      apoptosis. But a PPARalpha agonist ciprofibrate did not affect the cell death.
      Ciglitazone caused reactive oxygen species (ROS) generation and ciglitazone
      induced cell death was prevented by antioxidants, suggesting an important role of
      ROS generation in the ciglitazone-induced cell death. ROS generation and cell
      death induced by ciglitazone were inhibited by the PPARgamma antagonist GW9662.
      Ciglitazone treatment caused activation of extracellular signal-regulated kinase
      (ERK) and p38. Activation of ERK was dependent on epidermal growth factor
      receptor (EGFR) and that of p38 was independent. Ciglitazone-induced cell death
      was significantly prevented by PD98059, an inhibitor of ERK upstream kinase
      MEK1/2, and SB203580, a p38 inhibitor. Ciglitazone treatment increased Bax
      expression and caused a loss of mitochondrial membrane potential, and its effect
      was prevented by N-acetylcysteine, PD98059, and SB203580. Ciglitazone induced
      caspase activation, which was prevented by PD98059 and SB203580. The general
      caspase inhibitor z-DEVD-FMK and the specific inhibitor of caspases-3 DEVD-CHO
      exerted the protective effect against the ciglitazone-induced cell death. The
      EGFR inhibitors AG1478 and suramin protected against the ciglitazone-induced cell
      death. Taken together, these findings suggest that the MAPK signaling pathways
      play an active role in mediating the ciglitazone-induced cell death of
      osteoblasts and function upstream of a mitochondria-dependent mechanism. These
      data may provide a novel insight into potential therapeutic strategies for
      treatment of osteoporosis.

PMID- 16616946
TI  - Immunogenicity and efficacy of immunodeficiency virus-like particles pseudotyped
      with the G protein of vesicular stomatitis virus.
AB  - Vaccination with exogenous antigens such as recombinant viral proteins,
      immunodeficiency virus-derived whole inactivated virus particles, or virus-like
      particles (VLP) has generally failed to provide sufficient protection in animal
      models for AIDS. Pseudotyping VLPs with the vesicular stomatitis virus G protein
      (VSV-G), which is known to mediate entry into dendritic cells, might allow more
      efficient stimulation of immune responses. Therefore, we pseudotyped
      noninfectious immunodeficiency virus-like particles with VSV-G and carried out a
      preliminary screen of their immunogenicity and vaccination efficacy.
      Incorporation of VSV-G into HIV-1 VLPs led to hundred-fold higher antibody titers
      to HIV-1 Gag and enhancement of T cell responses in mice. Repeated vaccination of
      rhesus monkeys for 65 weeks with VSV-G pseudotyped simian immunodeficiency virus
      (SIV)-like particles (VLP[G]) provided initial evidence for efficient suppression
      of viral load after mucosal challenge with the SIVmac239 virus. Challenge of
      monkeys after a 28 week vaccination regimen with VLP[G] led to a reduction in
      peak viremia, but persistent suppression of viral load was not achieved. Due to
      limitations in the number of animals available for this study, improved efficacy
      of VSV-G pseudotyped VLPs in nonhuman primates could not be demonstrated.
      However, mouse experiments revealed that pseudotyping of VLPs with fusion
      competent VSV-G clearly improves their immunogenicity. Additional strategies,
      particularly adjuvants, should be considered to provide greater protection
      against a challenge with pathogenic immunodeficiency virus.

PMID- 16616947
TI  - Chimeras between SRS and Moloney murine leukemia viruses reveal novel
      determinants in disease specificity and MCF recombinant formation.
AB  - SRS 19-6 MuLV is a murine retrovirus originally isolated in mainland China. A
      noteworthy feature of this virus (referred to as SRS MuLV here) induces tumors of
      multiple hematopoietic lineages, including myeloid, erythroid, T-lymphoid and B
      lymphoid. To identify the determinants of disease specificity, chimeras between
      SRS and Moloney MuLV (M-MuLV) were generated by molecular cloning, and the
      pathogenic properties of the chimeras were investigated. The results indicated
      that, while the M-MuLV LTR can confer lymphoid specificity to SRS MuLV, the SRS
      LTR by itself was not sufficient to confer multiple lineage tumorigenesis to M
      MuLV; additional sequences in gag or pol were also required. Thus, a secondary
      determinant for myeloid/erythroid leukemia in SRS MuLV is located in gag-pol. In
      these chimeras, an independent determinant for T-lymphoma was found in M-MuLV gag
      pol. It was also interesting that insertion of M-MuLV env into SRS MuLV decreased
      the rate of leukemogenicity, while insertion of SRS env into M-MuLV (SEM)
      accelerated leukemogenesis. The enhanced pathogenicity of SEM was found to
      correlate with earlier formation of MCF recombinants. The basis for the
      accelerated MCF recombinant formation was investigated. The endogenous polytropic
      MuLV env sequences contributing to several SEM MCF recombinants were identified,
      and the cross-over points were identified. While no obvious differences in the
      relative homologies between SRS MuLV env and polytropic env vs. M-MuLV and
      polytropic envs suggested a reason for the more rapid MCF recombinant formation,
      an overlapping but different set of polytropic env proviruses were found to
      participate in MCF formation for M-MuLV vs. SEM. Thus, the mechanisms for MCF
      formation appear to differ for M-MuLV and SEM.

PMID- 16616948
TI  - Polyphosphate buffering by biomass with different phosphorus contents.
AB  - Polyphosphate buffering is a novel application of enhanced biological phosphorus
      (P) removal (EBPR) for P-deficient wastewaters with influent organic load
      variability. This study investigated the effect of biomass P content on
      polyphosphate buffering using a membrane bioreactor (MBR) and conventional
      bioreactor (CBR). Increasing the biomass P content increased polyphosphate
      buffering and the COD removal capacity, but at high P content (i.e. 20% P/TSS)
      the effluent P levels increased and a smaller fraction of available P was used
      for buffering. The MBR produced lower total effluent TSS levels and lower P
      levels than the CBR at both medium biomass P content (i.e. 12% P/TSS) and at low
      P content (i.e. 5% P/TSS) when the COD removal capacity was not exceeded. At high
      biomass P content, the MBR and CBR produced elevated effluent P levels. This
      study showed that the MBR does not make polyphosphate buffering feasible at high
      P content.

PMID- 16616949
TI  - Mineralization of alkylbenzenesulfonates in water by means of contact glow
      discharge electrolysis.
AB  - Mineralization of aqueous alkylbenzenesulfonates (ABS) was investigated by means
      of contact glow discharge electrolysis (CGDE). Toluenesulfonic and
      dodecylbenzenesulfonic acids in a neutral phosphate buffer solution were smoothly
      degraded and eventually converted to inorganic carbon and sulfate ion when CGDE
      was conducted under the applied DC voltage of 500 V and current of ca. 90 mA. As
      the intermediate products, some phenolic compounds were detected as well as
      carboxylic acids such as oxalate, formate and so on. It was demonstrated that the
      decay of ABS followed the first-order rate law. Based on the detailed analysis of
      the hydroxylation products and kinetic consideration, it was assumed that
      hydroxyl radicals would play a crucial role in the oxidative degradation of
      aqueous ABS. The features of CGDE as a tool for the removal of organic pollutants
      in water were discussed in comparison with other physicochemical methods.

PMID- 16616950
TI  - Enhanced hydrolysis of carbohydrates in primary sludge under biosulfidogenic
      conditions.
AB  - The potential for using readily available and cost-effective complex carbon
      sources, such as primary sludge (PS), for the bioremediation of sulfate-rich
      effluent streams, including acid mine drainage, has been constrained by the slow
      rate of solubilization and low yield of soluble products. Disposal of PS also
      remains a global problem. Recent studies of a patented recycling sludge bed
      reactor have shown that the solubilization of PS is enhanced under
      biosulfidogenic conditions. The current study investigated the enhanced
      solubilization of the carbohydrate fraction of PS under these conditions, using
      selective metabolic inhibitors. The mean maximum rate of reducing sugar
      production was significantly higher under sulfidogenic (167 mg L(-1)h(-1)) than
      methanogenic (51 mg L(-1)h(-1)) conditions and the utilization of volatile fatty
      acids under sulfidogenic conditions was rapid. Analysis of VFA profiles indicated
      preferential utilization of longer chain acids under sulfidogenic conditions and
      of acetate in the methanogenic systems and that the acetogenic step was unlikely
      to be rate-limiting in the solubilization of complex carbon.

PMID- 16616951
TI  - Suppression of food intake and food-reinforced behavior produced by the novel CB1
      receptor antagonist/inverse agonist AM 1387.
AB  - Cannabinoid CB1 receptor antagonist/inverse agonists are becoming increasingly
      recognized for their potential therapeutic utility as appetite suppressants. In
      the current paper we characterize the biochemical and behavioral effects of AM
      1387, which is a novel CB1 antagonist. AM 1387 exhibited binding affinity and
      selectivity for the CB1 over the CB2 receptor. Moreover, AM 1387 decreased
      GTPgammaS (EC50: 22.82 nM) and increased forskolin-stimulated cAMP (EC50: 274.6
      nM), as did the CB1 inverse agonist AM 251 (GTPgammaS EC50: 25.82 nM; cAMP EC50:
      363.8 nM), indicating that AM1387 also has inverse agonist properties in vitro.
      In the behavioral characterization in rats, AM 1387 suppressed lever pressing for
      food on two operant schedules (fixed-ratio 1 and 5). Timecourse of the effect on
      fixed-ratio 5 responding was then determined, and the half-life (t1/2=4.87 h) was
      found to be threefold shorter than what has been shown for SR 141716A, and
      fourfold shorter than AM 251. Finally, AM 1387 was found to suppress food intake
      using three diets of differing macronutrient composition and palatability. It was
      concluded that AM 1387 may be a useful tool for examining the effects of CB1
      receptor antagonism or inverse agonism on food intake.

PMID- 16616952
TI  - Expression of enzymes of cyclooxygenase pathway and secretion of prostaglandin E2
      and F2alpha by porcine myometrium during luteolysis and early pregnancy.
AB  - Past studies of uterine prostaglandin (PGs) and pig reproduction have focused on
      endometrial rather than myometrial PGs. This study documents the synthesis and
      secretion of myometrial prostaglandins (PGs) in pigs and the involvement of
      oxytocin (OT) in these processes. Cyclooxygenase-2 (COX-2) expression was similar
      in myometrial explants from cyclic and pregnant pigs (days 14-16) and OT (10(-7)
      M) in vitro significantly increased COX-2 protein regardless of reproductive
      state. Basal expression of prostaglandin E2 synthase (PGES) was higher during
      pregnancy than during luteolysis. Conversely, prostaglandin F synthase (PGFS) was
      highest during luteolysis and lower in myometrium from gravid animals. OT had no
      influence on the expression of PGES and PGFS. In another tissue culture
      experiment, myometrial slices produced more PGE2 than PGF2alpha regardless of
      reproductive state of the female. OT stimulated PGE2 production in myometrium
      harvested during luteolysis and increased PGF2alpha production in all tissues
      examined. Progesterone (P4; 10(-5) M) blocked stimulatory effect of OT on
      myometrial PG release. Myometrial OTr mRNA was higher (P=0.03) during luteolysis
      than during pregnancy. IN CONCLUSION: (1) oxytocin increases myometrial COX-2
      expression, but does not influence the expression of terminal enzymes of PGs
      synthesis (PGES and PGFS); (2) porcine myometrium preferentially produces PGs
      during early pregnancy and secretes more PGE2 than PGF2alpha; (3) myometrial OT
      and OTr support secretion of PGs from myometrium during luteolysis.

PMID- 16616953
TI  - Human exclusion from rocky shores in a mediterranean marine protected area (MPA):
      an opportunity to investigate the effects of trampling.
AB  - The effect of human trampling on the abundance of small invertebrates inhabiting
      rocky shallow bottoms was studied at Asinara Island MPA. To this aim we have
      conducted two experiments. The first was a quantitative study and tested the
      hypothesis that small invertebrates are more abundant at no-entry locations than
      at the location visited by tourists through time (before, during and after
      tourist season). The second was a manipulative experiment and tested the
      hypothesis that the abundance of small invertebrates is indirectly related to
      experimental trampling intensities. The effect due to tourist visitation was not
      highlighted on overall assemblages, suggesting that present seasonal tourist load
      at the MPA does not cause a significantly negative effect on the zoobenthic
      community studied. Although tourists exhibited trampling activity at the visited
      location, none of taxa examined showed a significant lower abundance during and
      strictly after the end of seasonal tourism peak in the visited location, rather
      than at control locations. However, results obtained with the second experiment
      suggested that the effects of different experimental trampling intensities on
      small invertebrates were variable among taxa. The experimental trampling caused
      immediate declines in the density of tanaids, nematodes, acari, bivalves,
      gammarids, echinoderms, isopods, and harpacticoids. For some of these taxa a
      recovery in abundance was observed within one month. This kind of data may offer
      important information to estimate the number of visitors compatible with the
      sensitivity of zoobenthic assemblages, and may substantially contribute to
      appropriate MPA management.

PMID- 16616954
TI  - DNA degradation with ozone.
AB  - DNA was ozonized in solution and the reaction was followed with polarimetry and
      with iodimetry. Polarimetry was used to determine the molar ratio DNA/O(3) when
      the DNA optical activity vanishes completely. At a molar ratio DNA/O(3)=2.3 the
      supramolecular structure of DNA collapses completely. Instead, iodimetry shows
      that the ozonolysis proceeds until all the nucleobases have been destroyed, an
      event which occurs at a molar ratio DNA/O(3)=1.1. The ozonolysis of DNA was also
      followed spectrophotometrically. DNA is reactive with ozone also in the solid
      state, as fixed bed. Clear indication about its oxidation derives from the FT-IR
      spectra from polarimetric measurements and from thermal analysis performed by
      thermogravimetric analysis (TGA), differential thermogravimetric analysis (DTG)
      and from differential thermal analysis (DTA). Particular remarkable is the fact
      that RNA has been found much less reactive toward ozone in the solid state than
      DNA.

PMID- 16616955
TI  - Comparison of antibody responses in Atlantic cod (Gadus morhua L.) to Aeromonas
      salmonicida and Vibrio anguillarum.
AB  - The immune system of Atlantic cod (Gadus morhua L.) differ from other bony fish
      species in that no or only very low increases in antibody levels are detected
      post-immunization with Vibrio salmonicida or V. anguillarum. Here, we report the
      results from the first study on comparison of antibody responses in cod to
      Aeromonas salmonicida and V. anguillarum. A. salmonicida appear to induce a
      stronger antibody response in cod compared to V. anguillarum, and more
      individuals immunized with A. salmonicida revealed a response compared to those
      immunized with V. anguillarum. The antibody responses to both bacterial species
      were mainly toward LPS, and the results indicate that cod antibodies are able to
      differentiate between LPS antigens from typical and atypical A. salmonicida
      strains.

PMID- 16616956
TI  - Phytotoxic effects of copper on nitrogen metabolism and plant growth in Brassica
      pekinensis Rupr.
AB  - Copper (Cu) from various anthropogenic and natural sources is one of the major
      heavy metal contaminants in the environment. To study Cu-induced nitrogen (N)
      metabolism damage in the popular vegetable Chinese cabbage (Brassica pekinensis
      Rupr.), aquatic culture experiments with this plant were performed. Two Cu levels
      (0.3 micromol/L (control) and 10.3 micromol/L) and two N levels (0.05- and 1-fold
      Hoagland's solution) were used for the aquatic culture experiments. The results
      demonstrated adverse effects of Cu on N metabolism and plant growth. Cu exposure
      elevated Cu concentration and decreased nitrate reductase (NR) activity in the
      roots and shoots and reduced total chlorophyll content. It also shortened root
      length and produced fewer leaves and lower plant biomass. However, Cu exposure
      increased total free amino acid content in the leaves. The results also
      demonstrated effects of N deficiency on N metabolism and plant growth. N
      deficiency increased the root/shoot ratio of biomass and the total free amino
      acid content and decreased the nitrate contents and NR activity in roots and
      leaves. In addition, there were interactive effects between Cu exposure and N
      level on plant biomass, root/shoot ratio, and chlorophyll and nitrate content in
      leaves. The results suggested that Cu toxicity to the plant was at least partly
      due to an influence on N metabolism.

PMID- 16616957
TI  - Reduction of 2,4-dichlorophenol toxicity to Pseudomonas putida after oxidative
      incubation with humic substances and a biomimetic catalyst.
AB  - The effect of a synthetic iron(III)-porphyrin meso-tetra(2,6-dichloro-3
      sulfonatophenyl)porphyrinate as a biomimetic catalyst in the oxidative treatment
      of 2,4-dichlorophenol (2,4-DCP) with humic substances and H(2)O(2) was evaluated
      in factorial design experiments conducted at different concentrations of 2,4-DCP
      (0-25 ppm) and different incubation treatment times (0, 24, 96, or 120 h). In the
      absence of this treatment, bioassays with the bacterium Pseudomonas putida
      (ATCC11250) showed decreasing specific growth rates mu (used here to quantify 2,4
      DCP toxicity) with increasing concentrations of 2,4-DCP. However, when 2,4-DCP
      was treated as mentioned above the toxicity of the resulting 2,4-DCP solution was
      reduced significantly. At low 2,4-DCP concentrations (up to 5 ppm) and long
      incubation periods (as long as 120 h), the specific growth rate mu was comparable
      to that of cultures grown in the absence of 2,4-DCP. The reduction in toxicity
      was directly correlated to a decrease in the concentration of 2,4-DCP in the
      treated solutions, as measured by high-performance liquid chromatography. The
      reduced concentrations of 2,4-DCP in the treated solutions could be correctly
      predicted based on the relationship between the specific growth rates and the 2,4
      DCP concentrations in untreated solutions. These results indicate that the
      oxidative coupling of 2,4-DCP to humic substances catalyzed by the synthetic
      iron(III)-porphyrin catalyst in the presence of H(2)O(2) is responsible for the
      removal of 2,4-DCP from solutions. This approach appears to be a promising
      alternative treatment to reduce 2,4-DCP bioavailability and thus toxicity in the
      environment.

PMID- 16616958
TI  - Turbot TNFalpha gene: molecular characterization and biological activity of the
      recombinant protein.
AB  - The tumor necrosis factor (TNF) superfamily is composed by several proteins with
      similar structure and functions. One of the main representatives of this family
      is TNF-alpha (TNFalpha), a proinflammatory cytokine which is produced by
      different immune cells and presents a wide variety of activities. Using the RACE
      technique, we have cloned and sequenced the turbot TNF cDNA. The analysis of its
      sequence showed several conserved motifs characteristic of members of the
      TNFalpha family. A phylogenetic tree constructed with different TNFs of fish and
      mammals grouped our sequence within the fish TNFalpha cluster. Therefore, the
      turbot TNF here studied was identified as TNFalpha. The complete TNFalpha gene
      was obtained by gene walking, and, similarly to the other known fish TNFalpha
      genes, presented three introns and four exons. A PCR was designed to study the
      turbot TNFalpha expression in vivo using as stimulus the bacteria Vibrio pelagius
      strain Hq222 and virus VHSV. The expression of the cytokine happened early after
      injection, and it was dependent on the pathogen injected and organ analyzed.
      Virus induced a higher TNFalpha expression, but this response was shorter in time
      than that induced by bacteria. In addition, TNFalpha expression was in general
      higher in kidney than in liver, as expected since the former is the
      haematopoietic organ of fish. The turbot recombinant TNFalpha (rTNFalpha) was
      obtained by IPTG induction of bacteria transformed with the pET15b-TNFalpha
      construct, and it was purified in native conditions. The recombinant protein was
      approximately 20 kDa in size, and its biological activity was assessed in vitro.
      No effect of the rTNFalpha neither alone nor in combination with LPS was observed
      on the chemiluminescence activity of turbot macrophages at any time tested.
      However, NO production was enhanced by the recombinant protein alone or with LPS
      72 h after the addition of the treatments. Finally, turbot rTNFalpha was able to
      recruit and activate inflammatory cells when injected in gilthead seabream,
      although to a lesser extent than gilthead seabream rTNFalpha.

PMID- 16616959
TI  - Pathophysiologic and therapeutic implications of adrenomedullin in cardiovascular
      disorders.
AB  - Adrenomedullin (AM) is a vasodilator peptide that originally isolated from
      pheochromocytoma tissue. However, the mRNA is expressed in the normal adrenal
      gland, heart, kidney and blood vessels. The human AM gene is located in the short
      arm of chromosome 11 and is composed of 4 exons. There are 2 single nucleotide
      polymorphisms in introns 1 and 3, and the 3'-end of the AM gene is flanked by a
      microsatellite marker of cytosine-adenine repeats that is associated with an
      increased risk of developing hypertension and diabetic nephropathy. AM gene
      expression is promoted by various stimuli, including inflammation, hypoxia,
      oxidative stress, mechanical stress and activation of the renin-angiotensin and
      sympathetic nervous systems. The AM gene promoter region possessed binding site
      for several transcription factors, including nuclear factor for interleukin-6
      expression (NF-IL6) and activator protein 2 (AP-2). Further, plasma AM levels are
      increased in patients with various cardiovascular diseases, including
      hypertension, heart failure and renal failure. These findings suggest that AM
      plays a role in the development of or response to cardiovascular disease. Indeed,
      experimental and clinical studies have demonstrated that systemic infusion of AM
      may have a therapeutic effect on myocardial infarction, heart failure and renal
      failure. Further, vasopeptidase inhibitors which augment the bioactivity of
      endogenous AM may benefit patients with hypertension and arteriosclerosis.
      Finally, the angiogenic and cytoprotective properties of AM may have utility in
      revascularization and infarcted myocardium and ischemic limbs. Because of the
      potential clinical benefits of AM, indications for use and optimal dosing
      strategies should be established.

PMID- 16616960
TI  - Role of cholesterol in the function and organization of G-protein coupled
      receptors.
AB  - Cholesterol is an essential component of eukaryotic membranes and plays a crucial
      role in membrane organization, dynamics and function. The modulatory role of
      cholesterol in the function of a number of membrane proteins is well established.
      This effect has been proposed to occur either due to a specific molecular
      interaction between cholesterol and membrane proteins or due to alterations in
      the membrane physical properties induced by the presence of cholesterol. The
      contemporary view regarding heterogeneity in cholesterol distribution in membrane
      domains that sequester certain types of membrane proteins while excluding others
      has further contributed to its significance in membrane protein function. The
      seven transmembrane domain G-protein coupled receptors (GPCRs) are among the
      largest protein families in mammals and represent approximately 2% of the total
      proteins coded by the human genome. Signal transduction events mediated by this
      class of proteins are the primary means by which cells communicate with and
      respond to their external environment. GPCRs therefore represent major targets
      for the development of novel drug candidates in all clinical areas. In view of
      their importance in cellular signaling, the interaction of cholesterol with such
      receptors represents an important determinant in functional studies of such
      receptors. This review focuses on the effect of cholesterol on the membrane
      organization and function of GPCRs from a variety of sources, with an emphasis on
      the more contemporary role of cholesterol in maintaining a domain-like
      organization of such receptors on the cell surface. Importantly, the recently
      reported role of cholesterol in the function and organization of the neuronal
      serotonin(1A) receptor, a representative of the GPCR family which is present
      endogenously in the hippocampal region of the brain, will be highlighted.

PMID- 16616961
TI  - Rapid detection and typing of influenza A and B by loop-mediated isothermal
      amplification: comparison with immunochromatography and virus isolation.
AB  - A reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) assay
      was established for the detection of influenza A virus H1 and H3 subtype strains
      and influenza B virus strains specifically. The total procedure from RNA
      extraction to virus typing was completed within 3h. In terms of specificity, the
      representative AH1, AH3 and B strains were detected only by strain-specific
      primers respectively. No cross-detection was observed. In terms of sensitivity,
      virus was detected at a minimum concentration of 10 ffu/ml. Eighty-three
      nasopharyngeal aspirates obtained from children diagnosed clinically with
      influenza were tested by the RT-LAMP assay, along with commercially available
      immunochromatography rapid diagnostic tests and by virus isolation. Virus was
      isolated from 78 samples (94%) and the subtype was determined by the
      hemagglutination inhibition test. Although it took at least 3 days, the detection
      sensitivity was the best of the three methods. With two rapid assays, the
      detection sensitivity of the RT-LAMP assay (85.5%) was higher than that of
      immunochromatography tests (75.9%). In addition, the RT-LAMP assay can be used to
      differentiate emerging influenza virus subtypes by selecting appropriate primer
      sets.

PMID- 16616962
TI  - Discovery of TSAO derivatives with an unusual HIV-1 activity/resistance profile.
AB  - The very first TSAO derivative that lacks the 4''-amino group at the 3'-spiro
      moiety (compound 3) has been prepared and the effect of this modification on the
      activity/resistance profile has been evaluated. This molecule proved HIV-1
      specific (NNRTI-characteristic). A mixture of wild-type and V106V/A or L234L/I
      mutations were found in the RT of some, but not all compound 3-resistant virus
      strains. Compound 3 does not select for the TSAO-specific E138K mutation in the
      RT. However, the compound markedly lost its antiviral potential against a variety
      of virus strains that contain NNRTI-characteristic mutations in RT including
      E138K. The deaminated TSAO compound must fit differently in the HIV-1 RT enzyme
      than its prototype TSAO-m(3)T.

PMID- 16616963
TI  - The number needed to treat in cardiovascular clinical trials.

PMID- 16616964
TI  - The contribution of peripheral and central vision in the control of movement
      amplitude.
AB  - Past research has revealed that central vision is more important than peripheral
      vision in controlling the amplitude of target-directed aiming movements. However,
      the extent to which central vision contributes to movement planning versus online
      control is unclear. Since participants usually fixate the target very early in
      the limb trajectory, the limb enters the central visual field during the late
      stages of movement. Hence, there may be insufficient time for central vision to
      be processed online to correct errors during movement execution. Instead,
      information from central vision may be processed offline and utilised as a form
      of knowledge of results, enhancing the programming of subsequent trials. In the
      present research, variability in limb trajectories was analysed to determine the
      extent to which peripheral and central vision is used to detect and correct
      errors during movement execution. Participants performed manual aiming movements
      of 450 ms under four different visual conditions: full vision, peripheral vision,
      central vision, no vision. The results revealed that participants utilised visual
      information from both the central and peripheral visual fields to adjust limb
      trajectories during movement execution. However, visual information from the
      central visual field was used more effectively to correct errors online compared
      to visual information from the peripheral visual field.

PMID- 16616965
TI  - Artisanal and experimental Pecorino Siciliano cheese: microbial dynamics during
      manufacture assessed by culturing and PCR-DGGE analyses.
AB  - Traditional artisanal Pecorino Siciliano (PS) cheeses, and two experimental PS
      cheeses were manufactured using either raw or pasteurised ewes' milk with the
      addition of starter cultures. The bacterial diversity and dynamics of the
      different cheese types were evaluated both by culturing and characterisation of
      isolates, and a culture-independent approach based on the 16S ribosomal RNA
      (rRNA) gene. Following cultivation, artisanal and experimental cheese types
      showed similar microbial counts, and isolates belonging to Lactococcus lactis,
      Streptococcus thermophilus, Enterococcus faecalis and Leuconostoc mesenteroides
      were identified by phenotypic characterisation and comparison of the restriction
      fragment length polymorphism (RFLP) of the 16S rRNA gene to that of reference
      species. The culture-independent fingerprinting technique PCR and denaturing
      gradient gel electrophoresis (DGGE) of V6 to V8 regions of the 16S rRNA gene of
      samples taken during artisanal PS cheese manufacture, from raw milk to the
      ripened cheese, indicated relevant shifts in the microbial community structure.
      The dominance of Streptococcus bovis and Lactococcus lactis species in the
      traditional artisanal PS was revealed by 16S rRNA gene sequencing. Comparison of
      DGGE profiles of samples from milk to ripened cheese, derived from artisanal
      procedure and the two experimental PS cheeses during production showed similar
      trends with the presence of intense bands in common. Nevertheless, the profiles
      of several artisanal cheeses from different farms appeared more diverse, and
      these additional species are probably responsible for the generally superior
      flavour and aroma development of traditional PS cheese.

PMID- 16616966
TI  - ortho- and meta-substituted aromatic thiols are efficient redox buffers that
      increase the folding rate of a disulfide-containing protein.
AB  - Thiol based redox buffers are used to enhance the folding rates of disulfide
      containing proteins in vitro. Traditionally, small molecule aliphatic thiols such
      as glutathione are employed. Recently, we have demonstrated that aromatic thiols
      can further enhance protein-folding rates. In the presence of para-substituted
      aromatic thiols the folding rate of a disulfide-containing protein was increased
      by 4-23 times over that measured for glutathione. However, several important
      practical issues remain to be addressed. Aromatic thiols have never been tested
      in the presence of denaturants such as guanidine hydrochloride. Only two of the
      para-substituted aromatic thiols previously examined are commercially available.
      To expand the number of aromatic thiols for protein folding, several commercially
      available meta- and ortho-substituted aromatic thiols were studied. Furthermore,
      an ortho-substituted aromatic thiol, easily obtained from inexpensive starting
      materials, was investigated. Folding rates of scrambled ribonuclease A at pH 6.0,
      7.0 and 7.7, with ortho- and meta-substituted aromatic thiols, were up to 10
      times greater than those with glutathione. In the presence of the common
      denaturant guanidine hydrochloride (0.5M) aromatic thiols provided 100% yield of
      active protein while maintaining equivalent folding rates.

PMID- 16616967
TI  - Conjugates of poly(DL-lactic acid) with ethylenediamino or diethylenetriamino
      bridged bis(beta-cyclodextrin)s and their nanoparticles as protein delivery
      systems.
AB  - Some biodegradable amphiphilic copolymers were synthesized by conjugating poly(DL
      lactic acid) (PLA) onto ethylenediamino or diethylenetriamino bridged bis(beta
      cyclodextrin)s (bis-CDs). Double emulsion (DE) and nanoprecipitation (NP) methods
      were used to fabricate the nanoparticles of these copolymers entrapping bovine
      serum albumin (BSA) as a model protein. Effects of the experimental parameters,
      such as copolymer composition, BSA concentration, copolymer concentration and
      poly(vinyl alcohol) concentration, on particular size and encapsulation
      efficiency (EE) were investigated. Their EE to BSA could reach 83.5% at an
      optimized condition owing to the cooperative binding effect of the CD moiety with
      BSA. The core-corona structure of copolymer micelles fabricated from the
      nanoprecipitation was studied on the basis of 1H NMR and other measurements at
      various temperatures. The results showed that the core-corona structure kept
      stable below 50 degrees C (lower than Tg). And increase of the micelle
      association number occurred above the Tg because the size of the NPs became
      larger and proton signals of the liquid-like PLA cores could be observed in 1H
      NMR in D2O at 60 degrees C. The release profiles of NPs showed a burst effect
      followed by a continuous release. Sodium dodecyl sulfate polyacrylamide gel
      electrophoresis, circular dichroic and fluorescence spectra were further used to
      identify the stability of BSA released from the NPs. The nanoparticles from the
      conjugates have a promising potential in nasal delivery system.

PMID- 16616968
TI  - Doubts on the diagnosis of type 2 diabetes in patients with hepatitis C virus
      infection.

PMID- 16616969
TI  - Drug-eluting stents: factors governing local pharmacokinetics.
AB  - Stent-based drug delivery system is a revolutionary approach to mitigate the
      negative affects of balloon angioplasty, improve immune responsiveness and
      prevent hyperplastic growth of smooth muscle in the restenotic state. Its success
      is therefore empirically associated with effective delivery of potent
      therapeutics to the target site at a therapeutic concentration, for a sufficient
      time, and in a biologically active form. However, local delivery with drug
      eluting stents imparts large dynamic concentration gradients across tissues that
      can be difficult to identify, characterize and control. This review explores the
      factors such as physiological transport forces, drug physicochemical properties,
      local biological tissue properties and stent design that governs the local
      pharmacokinetics within the arterial wall by drug-eluting stent. Rational design
      and optimization of drug-eluting stents for local delivery thus requires a
      careful consideration of all these factors.

PMID- 16616970
TI  - Cucumber carbohydrate metabolism and translocation under chilling night
      temperature.
AB  - A cold-tolerant line (NY-1) and a cold-sensitive cultivar (Jinyan 4) of cucumber
      (Cucumis sativus) were treated with temperatures of 28 degrees C/22 degrees C or
      28 degrees C/12 degrees C (day/night) in a 10-h photoperiod. Carbohydrates and
      related enzymes were assayed from 0 to 4 h after the start of the dark period.
      Compared to the normal night temperature (22 degrees C, control), sucrose,
      stachyose and galactinol increased in mature leaves under cold-night treatment
      (12 degrees C) while sucrose, glucose and fructose in fruits remained unchanged.
      In peduncles, where stachyose is catabolized to sucrose after long-distance
      transport, cold nights simultaneously induced a significant increase of stachyose
      (substrate) and a decrease of sucrose (product), indicating that the metabolic
      step from stachyose to sucrose in peduncles is crucial to translocation
      inhibition in cold nights. This decrease was more pronounced in the cold
      sensitive cultivar. Similar growth rates of fruits on one-fruit and two-fruit
      plants under cold-night treatment further confirmed that it is sink activity
      rather than source supply that is limiting the source-sink translocation. No
      significant genotypic differences in enzyme activities involved in the stachyose
      sucrose conversion, including alkaline alpha-galactosidase, acid alpha
      galactosidase, galactokinase, uridine diphosphate (UDP)-galactose
      pyrophosphorylase, UDP-glucose-4'-epimerase and sucrose synthase, were observed
      when assayed in an adenosine triphosphate (ATP)-rich in vitro environment.
      However, the ATP concentration was much higher in peduncles of the cold-tolerant
      line, indicating that a limiting ATP supply may be partially responsible for the
      stronger inhibition of the stachyose-sucrose pathway observed in the cold
      sensitive cultivar (Jinyan 4).

PMID- 16616971
TI  - Fermentation metabolism in roots of wheat seedlings after hypoxic pre-treatment
      in different anoxic incubation systems.
AB  - A hypoxic pre-treatment (HPT) can improve the anoxic survival of flooding
      sensitive plants. Here, we tested whether a 4-d HPT of wheat plants (Triticum
      aestivum L.) would improve their anoxic resistance, and if so, why. We found that
      the metabolic adjustment during prolonged HPT involved an increased lactate
      excretion rate, the up-regulation of glycolytic and fermentative enzymes as well
      as the accumulation of various sugars. Therefore, HPT wheat roots could sustain a
      3 times higher ethanolic fermentation rate during an anoxic period compared to
      non-pre-treated (NHPT) roots. Nevertheless, the enhanced fermentation rate
      provided temporary relief to the energy crisis only, and both NHPT and HPT plants
      died after 5d of anoxia in illumination. Comparison of different low oxygen
      incubation systems using excised roots or roots of intact plants revealed
      striking differences. The benefits of intact shoots, oxygen transport as well as
      additional sugar supply enabled a more stable energy supply of anoxia-treated
      NHPT and HPT roots. However, the height of the fermentation rate was correlated
      with a high ATP content during dark anoxic incubation, but not in illumination.

PMID- 16616972
TI  - Mass spectrometrical identification of brain proteins including highly insoluble
      and transmembrane proteins.
AB  - Conventional two-dimensional electrophoresis (2DE) is the main technique used for
      protein profiling of tissues and cells, however separation of strongly acidic,
      basic or highly insoluble proteins is still limited. A series of methods have
      been proposed to cope with this problem and the use of discontinuous gel
      electrophoresis in an acidic buffer system using the cationic detergent
      benzyldimethyl-n-hexadecylammonium chloride (16-BAC) with subsequent SDS-PAGE
      followed by mass spectrometry showed that results from 2DE can be complemented by
      this approach. It was the aim of this study to separate and identify proteins
      from whole mouse brain that were not demonstrated by 2DE. For this purpose
      samples were homogenised, soluble proteins were removed by ultracentrifugation
      and the water-insoluble pellet was resuspended in a mixture containing urea, 16
      BAC, glycerol, pyronine Y and dithiothreitol. Electrophoresis was run in the
      presence of 16-BAC, the strip from the gel containing separated proteins was cut
      out and was re-run on SDS-PAGE. Protein spots were analyzed by MALDI-TOF-TOF mass
      spectrometry. One hundred and six individual proteins represented by 187 spots
      were unambiguously identified consisting of 42 proteins with predicted pI values
      of pI>8.0, 25 with a 6.0<pI<8.0 and 39 with a pI<6.0. Twelve proteins with
      transmembrane domains (ranging from 1 to 8) including channels and carriers were
      identified. The generated map revealed a series of important brain proteins that
      were not separated and identified previously. Therefore, this system may be
      relevant for protein chemical determination of channels and carriers independent
      of antibody availability and specificity. The fact that transmembrane, basic,
      acidic as well as hydrophobic proteins with a positive Gravy Index can be
      resolved warrants work on further improvement of this analytical tool.

PMID- 16616973
TI  - Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate
      vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination
      vaccine in healthy infants.
AB  - BACKGROUND: To evaluate immunogenicity, reactogenicity, and safety of a
      hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B
      inactivated polio virus-Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when
      coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). METHODS:
      Infants received either a hexavalent diphtheria-tetanus-acellular pertussis
      hepatitis B-inactivated polio virus-H. influenzae type b vaccine concomitantly
      with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months
      (primary immunization) and 12-15 months of age (booster dose). Local and systemic
      reactions and adverse events were monitored following each dose and compared
      between groups. Blood was obtained prior to dose 1, one month after dose 3,
      immediately prior to and 1 month following the booster dose to measure antibody
      responses to each of the antigens. RESULTS: Two hundred and fifty-three subjects
      (PCV7, 127; Control, 126) were enrolled. Antibody responses were compared in 226
      subjects for the primary immunization and 212 for the booster dose (per-protocol
      (PP) population). Although there were some differences in geometric mean
      concentrations (GMCs) to the DTPa-HBV-IPV/Hib antigens after the primary series,
      GMCs for all antigens after the booster dose were similar in both groups, except
      for diphtheria which was significantly higher in the PCV7 group (PCV7, 7.41
      IU/mL; Control, 5.78 IU/mL). Reactogenicity and safety data were compared in 252
      infants receiving primary immunization and 235 children receiving the booster
      dose. Site reactions were similar in both groups. Fever >or=38.0 degrees C
      following each vaccination was reported more frequently in the PCV7 group (28.3
      50.0%) than in the Control group (15.6-33.6%) whereas fever >39.0 degrees C
      occurred only in a few cases and to the same extent in both groups (PCV7, 0.8
      2.7%; Control, 1.6-4.1%). Only one reported serious adverse event was
      characterized as being related to the study vaccines: control subject was
      hospitalized with a fever. CONCLUSION: DTPa-HBV-IPV/Hib and PCV7 were highly
      immunogenic, well-tolerated and safe when coadministered at 2, 3 and 4 months of
      age with a booster dose at 12-15 months of age. These results support the
      coadministration of PVC7 with DTPa-HBV-IPV/Hib as part of the routine
      immunization schedule for infants and children.

PMID- 16616974
TI  - An immunogenicity study of a newly fusion protein Cna-FnBP vaccinated against
      Staphylococcus aureus infections in a mice model.
AB  - Adhesins are considered the most important virulence factors during early phase
      Staphylococcus aureus infection. The present report describes a newly fusion
      protein, named Cna-FnBP that was constructed by fusion of the fnb and cna genes
      of S. aureus and expressed in E. coli. The recombinant protein was designed to
      broaden the function spectrum of block binding activity to S. aureus adhesion.
      Vaccination of the recombinant protein induced a strong and specific humoral
      response to Cna-FnBP in mice. In addition, splenocyte proliferation was provoked
      by in vitro stimulation with recombinant Cna-FnBP, thus, indicating direct
      implication of these cells in the immune response. These pre-incubated bacteria
      were phagocytosed by neutrophils at an increased level in vitro in a mouse model.
      Mice immunized with Cna-FnBP survived significantly longer following the
      challenge with S. aureus than nonimmunized mice did. These results indicate that
      Cna-FnBP is a promising vaccine for the prevention of S. aureus infections.
      Overall, the results suggest that fusion compounds which elicted from ECM-binding
      proteins (ECMBPs) were used to immunize against adhesins represents a valuable
      approach to combat S. aureus infections.

PMID- 16616975
TI  - Passive immunization with human anti-protein D antibodies induced by
      polysaccharide protein D conjugates protects chinchillas against otitis media
      after intranasal challenge with Haemophilus influenzae.
AB  - Passive transfer of a pediatric human serum pool generated against polysaccharide
      protein D conjugate vaccines conferred approximately 34% protection against
      development of ascending NTHI-induced OM when used in a chinchilla viral
      bacterial co-infection model. These data are in line with results obtained using
      a similar 11-valent-protein D conjugate vaccine in a pediatric clinical trial,
      wherein a vaccine efficacy of 35.6% was shown against acute OM episodes caused by
      NTHI. These observations strongly support the chinchilla passive transfer
      superinfection model as one that could predict clinical trials outcomes for
      vaccines to prevent NTHI-induced OM.

PMID- 16616976
TI  - MRSA pyogenic flexor tenosynovitis leading to digital ischaemic necrosis and
      amputation.

PMID- 16616977
TI  - Re: delayed single Kirschner wire compression technique for mallet fracture. D.
      Fritz, M. Lutz, R. Arora, M. Gabl et al., Journal of Hand Surgery 2005; 30: 180
      184.

PMID- 16616978
TI  - Using a mobile phone alarm for tourniquet timing.

PMID- 16616979
TI  - Treatment of fractures of the humeral capitellum using herbert screws.
AB  - Isolated fractures of the capitellum are rare injuries and account for 1% of all
      elbow injuries. The purpose of this study is to evaluate the clinical outcomes of
      11 Type I capitellum fractures treated by open reduction and internal fixation
      using at least two standard Herbert screws between 1998 and 2003. The average age
      of the patients was 27.5 years. The mean follow-up time was 23.4 months. The
      final postoperative assessment was made at the 12th month. The results were
      evaluated according to the Mayo Elbow Performance Index. We obtained excellent
      result in eight patients and good result in three patients. We recommend open
      reduction and fixation with Herbert screws inserted from the posterior surface of
      the lateral epicondyle and early mobilization in Type I fractures of the
      capitellum.

PMID- 16616981
TI  - Effects of long-term methylphenidate treatment: a pilot follow-up clinical and
      SPECT study.
AB  - BACKGROUND: Although abnormalities in the regional cerebral blood flow (rCBF)
      responses to methylphenidate (MPH) treatment have been reported in children with
      attention deficit hyperactivity disorder (ADHD), there are few prospective
      longitudinal studies assessing the long-term effects of MPH and discontinuation
      effects after chronic treatment. METHODS: The authors studied ten drug-naive
      children (2 girls, 8 boys, mean age+/-S.D.=9.60+/-1.96) diagnosed with ADHD by
      the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnostic
      criteria, using (99m)Tc-HMPAO-single photon emission computed tomography (SPECT).
      Patients were studied at baseline (visit 1), after 2 months of MPH treatment
      (visit 2) and after a drug-free period of 2 months following 12 months of MPH
      treatment (visit 3) at doses of 1 mg/kg/day. We evaluated SPECT data visually and
      semi-quantitatively. RESULTS: Two months of chronic MPH treatment resulted in
      visually detectable improvement in hypoperfusion in the right frontal cortex and
      all areas of temporal cortex with the exception of left lateral temporal cortex.
      This improvement was still detectable on visual evaluations of SPECT data after 2
      months of treatment discontinuation. The treatment effects that were detected
      visually were not statistically significant in semi-quantitative analyses.
      CONCLUSIONS: Treatment effects of chronic MPH treatment may persist long after
      the discontinuation of the treatment.

PMID- 16616982
TI  - Cytokines and serotonin transporter in patients with major depression.
AB  - Altered cytokine secretion as a mechanism in the etiology of depression is still
      obscure. The serotonin transporter (5-HTT) may play an important role in the
      termination of serotonergic neurotransmission by serotonin (5-HT) uptaking into
      presynaptic neurons and representing as an initial action site for selective 5
      HTT reuptake inhibitors (SSRI). In our study, we evaluated whether cytokines and
      5-HTT acted as biological markers for depression. Blood samples were collected
      from 42 participants. The differences in cytokine and 5-HTT mRNA expressions of
      leukocytes were assessed between the patients with major depression (n=20) and
      the healthy controls (n=22), along with the measurements prior and after
      treatment with a SSRI, fluoxetine, for 3 months in the follow-up patient group
      (n=8). The results revealed that the mRNA expressions of IL-1beta, IL-6,
      IFNgamma, TNFalpha, and 5-HTT were higher in the depressed patients than those of
      the healthy controls. The higher level of mRNA expressions of IFNgamma and 5-HTT
      diminished after fluoxetine treatment. Furthermore, we found a positive
      correlation between 5-HTT and cytokines mRNA expressions in total participants,
      which suggested that pro-inflammatory cytokines and 5-HTT might play critical
      roles in the pathogenesis of major depression and that their levels were affected
      by chronic treatment with 5-HTT inhibitors.

PMID- 16616983
TI  - Decreased serum semicarbazide sensitive aminooxidase (SSAO) activity in patients
      with major depression.
AB  - Semicarbazide sensitive aminooxidase (SSAO) is known to interplay with monoamine
      oxidases (MAO) and several antidepressants. Taking into account the monoamine
      hypothesis concerning the pathophysiology of depression, the aim of the present
      pilot study was to evaluate serum SSAO activity in depressed patients. A total of
      21 inpatients with major depression and 41 healthy controls were studied. Serum
      SSAO activity was determined by HPLC on days 1, 5 and 10 of inpatient treatment.
      At baseline without medication including antidepressants, highly depressed
      patients (MADRS score>or=30) had significantly decreased serum SSAO activity
      (mean 385+/-161 mU/l) when compared to healthy controls (mean 526+/-141 mU/l;
      p=0.003). This SSAO decrease was less pronounced at day 5 and day 10 under an
      antidepressive drug regime. Decreased serum SSAO activity was observed in
      patients with major depression, especially in those with high MADRS scores. The
      present results support the hypothesis of dysfunctional monoaminergic metabolism
      in the pathogenesis of depressive disorders. The disputable association between
      depression and monoamine metabolism requires further investigation, particularly
      with regard to SSAO activity and medication status.

PMID- 16616984
TI  - Postnatal exposure to diisopropylfluorophosphate enhances discrimination learning
      in adult mice.
AB  - Visual discrimination and reversal learning were tested in adult C57Bl/6 mice
      that had been treated on postnatal days (PND) 4-10 with
      diisopropylfluorophosphate (DFP), an acetylcholinesterase inhibitor. DFP-treated
      mice attained the learning criterion in the Y maze significantly earlier than
      saline-treated mice. Female mice treated with DFP showed a more rapid decline in
      errors in the initial discrimination task, compared to female mice treated with
      saline. There was no effect of DFP treatment on learning the reverse
      discrimination. The data suggest that long-lasting effects of treatment with an
      acetylcholinesterase inhibitor can improve discrimination learning, similarly to
      the improvement reported by acute administration in adults.

PMID- 16616985
TI  - The emotional consequences of social pragmatism: the psychophysiological
      correlates of self-monitoring.
AB  - Self-monitoring refers to the extent to which people regulate their self
      presentation by tailoring their behaviors to social situations. To examine the
      psychophysiological correlates of self-monitoring, we measured heart rate, skin
      conductance level, and EEG alpha of the frontal and parietal scalp regions during
      baseline and while anticipating an impromptu speech task. High self-monitors
      showed lower cortical activity in the frontal and parietal scalp regions than low
      self-monitors. Furthermore, self-monitoring scores were negatively correlated
      with skin conductance level when anticipating social threat. Social anxiety and
      depression did not account for these results. The findings suggest that high self
      monitors show lower autonomic and cortical arousal than low self-monitors when
      anticipating social stress.

PMID- 16616986
TI  - Cattle-rangeland management practices and perceptions of pastoralists towards
      rangeland degradation in the Borana zone of southern Ethiopia.
AB  - A survey was conducted in the Borana pastoral areas of southern Ethiopia to
      assess current livestock production systems, rangeland management practices and
      the perceptions of the pastoralists towards rangeland degradation. This
      information is considered vital to future pastoral development planning and
      interventions. Data were collected from a total of 20 villages that were
      identified from 5 peasant associations, namely Did Yabello, Moyatte, Did Harra,
      Dubuluk and Melbana. The average household size in the study area was 7.23. The
      majority of the pastoralists relied on both livestock and crop farming. The
      average livestock holding per household was 14 cattle, 10 goats, 6 sheep and 2
      camels. Livestock holdings, with the exception of camels, has shown a declining
      trend over time. The two most important traditional rangeland management
      strategies adopted by the pastoralists included burning and mobility, but since
      1974/75 burning has no longer been practised. With regard to mobility, the
      livestock herding falls in two categories, namely: home based and satellite
      herding. The former involves the herding of milking cows, calves and immature
      animals (<2 years) close to the encampments. The latter constitutes the herding
      of bulls and immatures (>2 years) further away from the encampments. Based on the
      pastoralists' perceptions, the major constraints on livestock production in
      descending order, were recurrent drought, feed and water scarcity, animal
      diseases, predators and communal land ownership. All the respondents considered
      the condition of the rangelands to have declined dramatically over time. In the
      past most development policies were based on equilibrium theories that opposed
      the communal use of the rangelands and traditional range management practices.
      The way in which the pastoral system affects the rangeland ecosystem functioning
      is contentious to this theory and the 'tragedy of the commons'. There was also a
      perceived problem of bush encroachment and the ban on traditional burning
      practices and recurrent droughts were seen as aggravating factors to this
      invasion process. The increasing practice of crop cultivation on the rangelands
      was identified as a serious threat to future livestock production and traditional
      resource management practices. Suggestions for possible interventions to improve
      the productivity and sustainable use of these rangelands are made.

PMID- 16616987
TI  - Effects of pH and cyclodextrins on pentachlorophenol degradation (mineralization)
      by white-rot fungi.
AB  - White-rot fungi (WRF) such as Trametes hirsuta completely degrade (mineralize)
      pentachlorophenol (PCP) and many other organopollutants. This has led to them
      being used to decontaminate various substrates (e.g. soil) through
      biorememediation. However, because PCP is a biocide, it can inhibit fungal growth
      and thereby its own degradation. It was hypothesized that substrate pH might
      affect PCP degradation, because when the pH is lower than 4.7 (the pKa for PCP)
      the phenol predominates, while at higher pH the phenate does. These two PCP
      species differ markedly in physical and biological properties. The effect of
      cyclodextrins was also investigated since it is known that the inclusion
      complexes these form with PCP differ in bioavailability and toxicity from non
      complexed PCP. Tests were first made in liquid and agar media (where conditions
      are relatively easy to control), and then in a sawdust, because it is a common
      target matrix for WRF bioremediation. Results with the liquid and agar media
      showed that growth in the presence of inhibitory PCP concentrations decreased as
      the pH decreased, consistent with the phenol being more toxic. Growth in sawdust
      was less affected by PCP regardless of the pH, presumably because the PCP sorbed
      to the wood which decreased its bioavailability. Some cyclodextrins markedly
      decreased the PCP's toxicity in liquid, agar and sawdust media. Rates of PCP
      mineralization (measured from production of (14)CO(2) from (14)C PCP) in liquid
      cultures containing 0.5 mgkg(-1) PCP (a sub-inhibitory concentration) were
      similar from pH 2.5-7.5, indicating that the phenol and the phenate were equally
      degradable. Degradation of a growth inhibiting concentration on sawdust (1,000
      mgkg(-1)) could be increased slightly by lowering the pH below the pKa, this
      increasing sorption to the wood. Degradation increased more when the pH was
      raised well above the pKa, presumably due to the phenate being less toxic and
      more soluble, making it more available to the degradative system. Although some
      cyclodextrins decreased growth inhibition, they also interfered with degradation.
      If this interference could be overcome, cyclodextrins could be used to increase
      the maximal PCP concentration that could be treated by WRF bioremediation.

PMID- 16616988
TI  - Determination of VOC source signature of vehicle exhaust in a traffic tunnel.
AB  - This study describes the methodology used to obtain the volatile organic compound
      (VOC) source signature of vehicle exhaust. To accomplish this, C(2)-C(9) VOCs
      were measured in a traffic tunnel located in Seoul, South Korea. The effect of
      VOC concentrations from the outside ambient air was considered in the
      determination of the source signature. To examine the effects of ambient air on
      VOC concentrations inside the tunnel, the ratio of propane to the total VOC
      concentrations was compared between the entrance and middle sites in the tunnel.
      Propane was used as a standard not only because of its insignificant contribution
      to vehicle exhaust gas, but also the fact that propane is the most abundant VOC
      in the atmosphere of Seoul. The ratio of propane to the total VOC concentrations
      was higher at the entrance site than at the middle location by, on average, 60%.
      This suggests that ambient air affects the inside tunnel air to a greater extent
      at the entrance site as compared to the middle site. The contribution of ambient
      air to the air inside the tunnel at the entrance location varied from 30% to 67%,
      with an average of 55%. This is 1.5 times higher than the value measured at the
      middle location, which ranged from 20% to 48%, with an average of 36%. This shows
      that ambient air substantially affects the inside air of the tunnel. Excluding
      the effects of ambient air on the air inside the tunnel can provide an improved
      chemical composition for vehicle exhaust using tunnel measurements. We believe
      that the concentration difference between the two sites within the tunnel
      provides a more accurate chemical composition of vehicle exhaust as compared to
      that obtained from a measurement taken at only one point inside the tunnel.

PMID- 16616989
TI  - Lack of significant association between -1021C-->T polymorphism in the dopamine
      beta hydroxylase gene and attention deficit hyperactivity disorder.
AB  - Recent trends in medications for attention deficit hyperactivity disorder (ADHD)
      suggest that norepinephrine (NE) deficiency may contribute to the disease
      etiology. Dopamine beta hydroxylase (DBH) is the key enzyme which converts
      dopamine to NE and since DBH gene is considered a major quantitative trait locus
      for plasma DBH activity, genetic polymorphism may lead to altered NE
      neurotransmission. Several polymorphisms including a 5' flanking -1021C-->T
      polymorphism, was reported to be associated with changed DBH activity and an
      association between -1021C-->T polymorphism with ADHD was observed in Han Chinese
      children. We have carried out family-based studies with three polymorphisms in
      the DBH gene, -1021C-->T polymorphism, exon 2*444g/a and intron 5 TaqI RFLP, to
      explore their association with Indian ADHD cases. Allele and genotype frequency
      of these polymorphisms in ADHD cases were compared with that of their parents and
      a control group. Haplotypes obtained were analyzed for linkage disequilibrium
      (LD). Haplotype-based haplotype relative risk analysis and transmission
      disequilibrium test showed lack of significant association between transmission
      of the polymorphisms and ADHD. A haplotype comprising of allele 1 of all
      polymorphisms showed a slight positive trend towards transmission from parents to
      ADHD probands. Strong LD was observed between *444g/a and TaqI RFLP in all the
      groups. However, low D' values and corresponding log of odds scores in the
      control group as compared to the ADHD families indicated that, the incidence of
      the two polymorphisms being transmitted together could be higher in ADHD
      families.

PMID- 16616990
TI  - Morphological and molecular characteristics of Echinococcus multilocularis and
      Echinococcus granulosus mixed infection in a dog from Xinjiang, China.
AB  - The Xinjiang plateau of western China has been shown to have a high prevalence
      for human cystic echinococcosis (CE) caused by Echinococcus granulosus, and human
      alveolar echinococcosis (AE) caused by Echinococcus multilocularis. The domestic
      dog is suspected to be the primary definitive host for the transmission of both
      E. granulosus and E. multilocularis to humans in this locality. Seventeen of 30
      stray dogs from Hejing County of Xinjiang were found positive for E. granulosus
      post mortem, and one double infection was suspected. Worm samples were collected,
      dyed by carmine, and observed microscopically. Carmine staining examination
      clearly revealed the differences in number of proglottids and appearance of
      uterine branches and lateral genital pore for those two species of Echinococcus.
      Furthermore, gene target DNA fragments were amplified for formal identification
      of the two parasite species, based on 12s rRNA mitochondrial gene. The PCR
      products were purified and sequenced. Compared with NCBI GenBank, the DNA
      sequences demonstrated 100% identity with E. granulosus (sheep strain, G1
      genotype) and E. multilocularis.

PMID- 16616991
TI  - Chemotherapy may have small to moderate negative effects on cognitive
      functioning.

PMID- 16616992
TI  - Arguments for a lower carbohydrate-higher fat diet in patients with a short small
      bowel.
AB  - Short small bowel patients suffer from malabsorption due to a strongly reduced
      small bowel surface. These patients usually get a high caloric high carbohydrate
      low fat diet at oral or enteral feeding. At several points our studies
      demonstrate that the effect of this formula is doubtful. In these patients the
      intestinal flora has strongly been changed and even become characteristic due to
      abundant presence of lactobacilli (up to nearly 100%). In many patients with a
      high carbohydrate-low fat diet these bacteria both produce massive amounts of d
      lactic acid and gaseous CO2, and they destroy the primary bile acids that are
      necessary for uptake of lipids. Thus, they cause (i) an increased risk of D
      lactic acidosis and D-lactic acid-associated encephalopathy, (ii) flatulence,
      abdominal pain and non-infectious diarrhoea, and (iii) low uptake of fat and
      lipophilic vitamins. It is argued that by gradually converting the diet to a low
      carbohydrate-high fat diet growth of the characteristic lactobacilli can be
      strongly reduced and so also the mentioned inconveniences.

PMID- 16616993
TI  - Further tests of the Scalar Expectancy Theory (SET) and the Learning-to-Time
      (LeT) model in a temporal bisection task.
AB  - To contrast two models of timing, Scalar Expectancy Theory (SET) and Learning to
      Time (LeT), pigeons were exposed to a double temporal bisection procedure. On
      half of the trials, they learned to choose a red key after a 1s signal and a
      green key after a 4s signal; on the other half of the trials, they learned to
      choose a blue key after a 4-s signal and a yellow key after a 16-s signal. This
      was Phase A of an ABA design. On Phase B, the pigeons were divided into two
      groups and exposed to a new bisection task in which the signals ranged from 1 to
      16s and the choice keys were blue and green. One group was reinforced for
      choosing blue after 1-s signals and green after 16-s signals and the other group
      was reinforced for the opposite mapping (green after 1-s signals and blue after
      16-s signals). Whereas SET predicted no differences between the groups, LeT
      predicted that the former group would learn the new discrimination faster than
      the latter group. The results were consistent with LeT. Finally, the pigeons
      returned to Phase A. Only LeT made specific predictions regarding the
      reacquisition of the four temporal discriminations. These predictions were only
      partly consistent with the results.

PMID- 16616994
TI  - Behavioral economic analysis of opioid consumption in heroin-dependent
      individuals: effects of unit price and pre-session drug supply.
AB  - Behavioral economic analysis has been used to investigate factors underlying drug
      consumption in laboratory animals and, increasingly, in human drug abusers.
      However, there are few studies in heroin abusers, especially those who are not in
      treatment; such studies may be valuable for understanding the mechanisms of
      persistent drug use. This study investigated effects of unit price (UP) and pre
      session supply of hydromorphone (HYD) on choice and consumption of HYD. Heroin
      dependent research volunteers (n=13) stabilized on buprenorphine 8 mg/day
      completed this eight-session inpatient study. In sessions 1-2, participants
      sampled two total HYD doses (12 and 24 mg IM) that could be earned in later
      sessions. In each of the final six sessions, volunteers were given access to a 12
      trial choice progressive ratio schedule lasting 3h. On each trial, volunteers
      could earn a HYD unit dose (1 or 2 mg, for a maximum of 12 or 24 mg,
      respectively) or money (US dollars 2, for a maximum of US dollars 24). Fixed
      ratio requirements increased exponentially, generating 24 unit prices for
      behavioral economic analysis. Before some choice sessions, volunteers could
      choose (FR 1) to receive extra HYD (12 or 24 mg; at 0915), whereas on other days
      no supplement was available. HYD choice and peak responding (breakpoint, O(max))
      measures increased with unit dose, decreased with pre-session supplements, and
      were greater among volunteers who used cocaine prior to the experiment. Taking
      pre-session supplements decreased P(max) and made group-percent HYD consumption
      more demand-elastic. Consumption was functionally equivalent at differing FR/unit
      dose combinations. Thus, opioid demand in heroin-dependent individuals not in
      treatment is a function of drug supply, unit price, and cocaine use.

PMID- 16616995
TI  - Zebrafish and chicken lipocalin-type prostaglandin D synthase homologues:
      Conservation of mammalian gene structure and binding ability for lipophilic
      molecules, and difference in expression profile and enzyme activity.
AB  - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is a bifunctional protein
      possessing both the ability to synthesize PGD(2) and to serve as a carrier
      protein for lipophilic molecules. L-PGDS has been extensively studied in
      mammalian species, whereas little is known about non-mammalian forms. Here, we
      identified and characterized the L-PGDS homologues from non-mammals such as
      zebrafish and chicken. Phylogenetic analysis revealed that L-PGDSs of mammalian
      and non-mammalian organisms form a "L-PGDS sub-family" that has been
      evolutionally separated from other lipocalin gene family proteins. The genes for
      zebrafish and chicken L-PGDS homologues consisted of 6 exons, and all of the
      exon/intron boundaries were completely identical to those of mammalian L-PGDS
      genes. Zebrafish and chicken L-PGDS genes were clustered with several lipocalin
      genes in the chromosome, as in the case of mouse and human genes. Gene expression
      profiles were different among chicken, mouse, human, except for conservation of
      abundant expression in the brain and heart. The chicken L-PGDS homologue carried
      weak PGDS activity, whereas the zebrafish protein did not show any of the
      activity. However, when the amino-terminal region of the zebrafish L-PGDS
      homologue was exchanged for that of mouse L-PGDS carrying the Cys residue
      essential for PGDS activity, this chimeric protein showed weak PGDS activity.
      Both zebrafish and chicken L-PGDS homologues bound thyroxine and all-trans
      retinoic acid, like mammalian L-PGDSs and other lipocalin gene family proteins.
      These results indicate that non-mammalian and mammalian L-PGDS genes evolved from
      the same ancestral gene and that the non-mammalian L-PGDS homologue was the
      primordial form of L-PGDS but whose major function was and is to serve as a
      carrier protein for lipophilic molecules. During molecular evolution, the
      mammalian L-PGDS protein might have acquired effective PGDS activity through
      substitution of several amino acid residues, especially in the amino-terminal
      region including the Cys residue, which is essential for PGDS activity.

PMID- 16616996
TI  - EST-based identification of genes expressed in the liver of adult seabass
      (Dicentrarchus labrax, L.).
AB  - The scarcity of the genomic resources for some fish species, in spite of their
      commercial interest, could retard the positive effects that modern biotechnology
      can offer to aquaculture industry. Then an effort should be made to reduce, as
      far as it concerns genomic resources, the gap that separates farming species from
      "model organisms". In this paper, we present an EST project in which we performed
      single pass sequencing on 1229 randomly selected clones from a sea bass cDNA
      library. The sequences are deposited in the NCBI database with the following
      accession numbers: from , from , from and from . EST cataloguing and profiling of
      seabass will set the basis for functional genomic research in this species, but
      will also serve for comparative and environmental genomics, for the
      identification of polymorphic markers useful, for example, to survey the disease
      resistance of fish, for the discovery of new molecular markers of exposure and
      for the production of micro- and macro-arrays.

PMID- 16616997
TI  - Highly synchronous and fertile reproductive activity induced by the male effect
      during deep anoestrus in lactating goats subjected to treatment with artificially
      long days followed by a natural photoperiod.
AB  - The response to the male effect was studied in two flocks of Saanen and three of
      Alpine goats during deep anoestrus in three consecutive years. Males and females
      were subjected to artificially long days for about 3 months (between December 4
      and April 1) followed by a natural photoperiod. Bucks joined goats 42-63 days
      after the end of the long days treatment (between April 20 and June 3) and
      fertilisation was ensured by natural mating. In experiment 1 (n=248), female
      goats were treated or untreated with melatonin at the end of the long days
      treatment and treated or untreated for 11 days with fluorogestone acetate (FGA)
      before teasing. The males received melatonin implants. In experiment 2 (n=337),
      the factor studied was the association or non-association of the 11-day FGA
      treatment. Neither males nor females received melatonin implants. In experiment 3
      (n=180), goats were treated for 11 days with FGA or with natural progesterone
      (CIDR). Neither males nor females received melatonin implants. In experiment 1,
      among the non-cycling goats (n=218), 99% ovulated and 81% kidded at 161+/-8 days
      after joining. Ninety-two percent of FGA-treated goats displayed an LH surge at
      65+/-11h after teasing. Melatonin treatment did not affect any parameter but FGA
      advanced the kidding date. In experiment 2, 94% of the goats ovulated and 87%
      kidded. A major peak of conception was observed on days 3 and 8 after joining in
      FGA-treated and untreated goats, respectively. Among the FGA-treated goats, 83%
      displayed an LH surge. Over all flocks, most of the LH surges occurred over a 24
      36 h interval, but the surge was initiated at different times in different flocks
      (36, 48 or 60 h after joining). FGA treatment did not influence the results,
      except for advancement of births of about 5 days. Differences among flocks were
      highly significant. In experiment 3, 94% of the goats displayed the LH surge, 93%
      ovulated and 68% kidded. Significant differences were found among flocks, but not
      between the FGA and CIDR groups. Bucks marked 85% of the goats 24-72 h after
      joining. The time interval between the detection of marked goats and detection of
      the LH surge depended on the time of marking (r=-0.62; p<0.05). In conclusion,
      treatment of both males and females goats with artificially long days followed by
      a natural photoperiod is very effective in inducing highly synchronous and
      fertile reproductive activity via the male effect in the middle of seasonal
      anoestrus.

PMID- 16616998
TI  - Comparative response of rams and bulls to long-term treatment with gonadotropin
      releasing hormone analogs.
AB  - The objective was to compare the relative response between rams and bulls in
      characteristics of LH, FSH and testosterone (T) secretion, during and after long
      term treatment with GnRH analogs. Animals were treated with GnRH agonist, GnRH
      antagonist, or vehicle (Control) for 28 days. Serial blood samples were collected
      on day 21 of treatment, and at several intervals after treatment. Injections of
      natural sequence GnRH were used to evaluate the capacity of the pituitary to
      release gonadotropins during and after treatment. Treatment with GnRH agonist
      increased basal LH and T concentrations in both rams and bulls, with a greater
      relative increase in bulls. Endogenous LH pulses and LH release after
      administration of GnRH were suppressed during treatment with GnRH agonist.
      Treatment with GnRH antagonist decreased mean hormone concentrations, LH and T
      pulse frequency, and the release of LH and T after exogenous GnRH, with greater
      relative effects in bulls. Rams previously treated with antagonist had a greater
      release of LH after administration of GnRH compared with control rams, while rams
      previously treated with agonist showed a reduced LH response. Bulls previously
      treated with agonist had reduced FSH concentrations and LH pulse amplitudes
      compared with control bulls while bulls previously treated with antagonist had
      greater T concentrations and pulse frequency. The present study was the first
      direct comparison between domestic species of the response in males to treatment
      with GnRH analogs. The findings demonstrated that differences do occur between
      rams and bulls in LH, FSH and testosterone secretion during and after treatment.
      Also, the consequences of treatment with either GnRH analog can persist for a
      considerable time after discontinuation of treatment.

PMID- 16616999
TI  - Epidermal nevus syndrome and intraspinal hemorrhage.
AB  - The epidermal nevus syndrome (ENS) is a rare neurocutaneous disease characterized
      by extensive epidermal nevi and a wide variety of abnormalities involving brain,
      eyes, and skeleton. Neurological symptoms in ENS include seizures, paresis, and
      mental retardation and are usually ascribed to hemimegalencephaly and various
      migration disorders. It was suggested that in some patients neurological symptoms
      might be secondary to vascular abnormalities. We report a case of a patient with
      diagnosed ENS without any primary CNS lesions, who developed paraplegia resulting
      from spinal cord hemorrhage. The patient presented many vascular and skeletal
      anomalies.

PMID- 16617000
TI  - Fibroblast screening for chaperone therapy in beta-galactosidosis.
AB  - We performed screening of beta-galactosidase-deficient fibroblasts for possible
      chemical chaperone therapy using N-octyl-4-epi-beta-valienamine (NOEV) in
      patients with GM1-gangliosidosis and Morquio B disease (beta-galactosidosis).
      Fibroblasts were cultured with NOEV for 4 days and beta-galactosidase activity
      was measured. Mutation analysis was performed simultaneously. Two separate
      criteria were set for evaluation of the chaperone effect: a relative increase of
      enzyme activity (more than 3-fold), and an increase up to more than 10% normal
      enzyme activity. Among the 50 fibroblast strains tested, more than 3-fold
      increase was achieved in 17 cell strains (34%), and more than 10% normal activity
      in 10 (20%). Both criteria were satisfied in 6 (12%), and either of them in 21
      (42%). Juvenile GM1-gangliosidosis was most responsive, and then infantile GM1
      gangliosidosis. This enhancement was mutation-specific. We estimate that the NOEV
      chaperone therapy will be effective in 20-40% of the patients, mainly in juvenile
      and infantile GM1-gangliosidosis patients. A molecular design may produce
      mutation-specific chaperone compounds for the other disease phenotypes. This
      cellular screening will be useful for identification of human patients with beta
      galactosidase deficiency for chaperone therapy to be started in the near future.

PMID- 16617001
TI  - Posterior reversible encephalopathy syndrome in a child with bronchial asthma.
AB  - Although posterior reversible encephalopathy syndrome (PRES) is caused by various
      conditions, there have been no reports on PRES associated with bronchial asthma.
      We report a case with PRES during the treatment for severe asthmatic attack. A 4
      year-old girl was treated for asthmatic attack with steroids. From the 10th
      hospital day, hypertension, pulmonary edema, and cardiomegaly were observed. In
      spite of treatment with furosemide, she became lethargic and had a generalized
      convulsion on the 23rd hospital day. CT showed low density areas in the bilateral
      occipital white matter and MRI on the 28th hospital day demonstrated high
      intensity areas in the same regions on T2-weighted and FLAIR images. After
      discontinuation of corticosteroid and further antihypertensive therapy, her
      consciousness improved. MRI on the 67th hospital day had no abnormalities and no
      neurological sequelae were seen at 2 years after the event. We should be aware
      that PRES is a rare but important adverse event related to steroid therapy,
      because hypertension and water retention are major adverse effects of steroids.

PMID- 16617002
TI  - Separation and characterization of clindamycin and related impurities in bulk
      drug by high-performance liquid chromatography-electrospray tandem mass
      spectrometry.
AB  - A simple high-performance liquid-electrospray ionization tandem mass
      spectrometric (HPLC-ESI-MSn) method has been developed for the rapid
      identification of clindamycin and its related minor impurities in bulk drug. The
      ESI-MSn results obtained allowed us to propose plausible schemes for their
      fragmentations, which were confirmed further by electrospray ionization Fourier
      transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS) using
      collision-induced dissociation (CID) method at high mass resolution. The positive
      ESI-MS/MS of clindamycin and its derivative compounds showed some diagnostic
      fragments, such as the neutral losses of H2O, HCl, methanethiol and 2-methylthio
      ethenol, and the residue of 3-propyl-N-methylpyrrolidine and 3-ethyl-N
      methylpyrrolidine, which are specific and useful for the identification of the
      lincosamide antibiotics and related impurities. According to the fragmentation
      mechanism of mass spectrometry and HPLC-UV-ESI-MSn data, six impurities of
      clindamycin have been identified on-line. Additionally, the positive ion mode
      extracted ion current (EIC) method has been used to separate and identify these
      lincosamide compounds.

PMID- 16617003
TI  - Quantitative prognostic indices in peritoneal carcinomatosis.
AB  - Five different descriptions quantitating peritoneal carcinomatosis are available:
      the Lyon staging system, the Peritoneal Cancer Index (PCI), the Japanese Research
      Society for Gastric Cancer carcinomatosis staging (JRSGS), the Dutch simplified
      peritoneal carcinomatosis assessment and the Completeness of Cytoreduction Score
      (CCR). These five staging systems are described and discussed. Combinations of
      these to achieve a complete description of peritoneal lesions prior to and
      following treatment assist in a correct prognostic assessment for these patients
      and in a selection of treatment options.

PMID- 16617004
TI  - Quantitative prognostic indicators of peritoneal dissemination of gastric cancer.
AB  - There are three classifications that describe the quantitative prognostic
      indicators of peritoneal dissemination for gastric cancer. The Japanese
      classification (P1, P2, and P3, Lyon classification, (stage I, II, stage III, and
      stage IV), and the Peritoneal Cancer Index (PCI). Carcinomatosis with limited
      extent (P1/ P2) corresponds to the PCI less than 13 and the stage I and II from
      Lyon classification. Carcinomatosis with large extent (P3) corresponds to PCI of
      13 or larger and stage III and IV from Lyon classification. PCI enables one to
      describe the precise distribution of peritoneal dissemination. All three
      classifications correlate with prognosis. With regard to the surgical
      cytoreduction of the primary tumor and the peritoneal dissemination, Sugarbaker
      proposed the classification of completeness of cytoreduction (CCR). Patients with
      no macroscopic residual tumor had significantly better prognosis than those with
      residual disease. CCR is a valuable prognostic indicator after cytoreductive
      surgery.

PMID- 16617005
TI  - Copy number polymorphisms are not a common feature of innate immune genes.
AB  - Extensive copy number polymorphism was recently reported for innate immunity
      related alpha-defensin genes DEFA1 and DEFA3 and beta-defensin genes DEFB4,
      DEFB103, and DEFB104. To establish whether such polymorphisms are a common
      feature of innate immune genes we used quantitative real-time PCR to determine
      the copy numbers of seven genes whose products have important innate immune
      functions. The genes encoding lysozyme, lactoferrin, cathelicidin antimicrobial
      peptide (hCAP18/LL-37), cathepsin G, bactericidal/permeability-increasing
      protein, azurocidin (CAP37/heparin-binding protein), and neutrophil elastase were
      each found to be single copy per haploid genome. These findings, along with the
      recent observation that defensin genes DEFA4, DEFA5, DEFA6, and DEFB1 are single
      copy, suggest that copy number polymorphisms are not a common feature of the
      innate immune genome but are restricted to a small subset of innate immunity
      related genes.

PMID- 16617006
TI  - Angiopoietins-1 and -2 are both capable of mediating endothelial PAF synthesis:
      intracellular signalling pathways.
AB  - Vascular endothelial growth factor (VEGF) is the only angiogenic growth factor
      capable of inducing an inflammatory response and we have recently demonstrated
      that its inflammatory effect is mediated by the endothelial synthesis of platelet
      activating factor (PAF). Recently discovered, Ang1 and Ang2, upon binding to Tie2
      receptor, modulate vascular permeability and integrity, contributing to
      angiogenesis. Ang1 was initially identified as a Tie2 agonist whereas Ang2 can
      behave as a context-dependent Tie2 agonist or antagonist. We sought to determine
      if Ang1 and/or Ang2 could modulate PAF synthesis in bovine aortic endothelial
      cells (BAEC) and if so, through which intracellular signalling pathways. Herein,
      we report that Ang1 and Ang2 (1 nM) are both capable of mediating a rapid Tie2
      phosphorylation and a rapid, progressive and sustained endothelial PAF synthesis
      maximal within 4 h (1695% and 851% increase, respectively). Angiopoietin-mediated
      endothelial PAF synthesis requires the activation of the p38 and p42/44 MAPKs,
      PI3K intracellular signalling pathways, and a secreted phospholipase A(2)
      (sPLA(2)-V). Furthermore, angiopoietin-mediated PAF synthesis is partly driven by
      a relocalization of endogenous VEGF to the cell surface membrane. Our results
      demonstrate that the angiopoietins constitute another class of angiogenic factors
      capable of mediating PAF synthesis which may contribute to proinflammatory
      activities.

PMID- 16617007
TI  - Chronic bile duct obstruction induces changes in plasma and hepatic levels of
      cytokines and nitric oxide in the rat.
AB  - Chronic bile duct ligation (BDL) is a useful model of cirrhosis. However, its
      parallel plasma and liver changes in levels of cytokines and nitric oxide (NO),
      involved in liver damage, remain unknown. The aims of this work were to quantify
      both the plasma and hepatic levels of five cytokines and NO in cirrhotic rats, 28
      days after bile BDL, and to analyze their relationship with liver damage markers.
      One group of male Wistar rats was bile duct ligated and another group was sham
      operated, both groups were sacrificed 28 days after BDL. Plasma and liver
      cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-6, -1beta, -10
      (IL-6, -1beta, -10) and interferon-gamma (IFN-gamma), were measured by ELISA.
      Plasma and hepatic NO was determined as NO(2)(-)+NO(3)(-) by an enzymatic method.
      Alkaline phosphatase, gamma-glutamyl transpeptidase, alanine aminotransferase and
      bilirubins were determined in plasma. Collagen, lipid peroxidation and glycogen
      were quantified in liver. Two histopathological staining techniques were
      performed. BDL-induced cirrhosis was corroborated by the elevated liver damage
      markers and histopathological analysis. Chronic BDL significantly increased
      (P<0.05) most of plasma and hepatic cytokine levels and diminished the hepatic
      IFN-gamma amount. NO was increased in both tissues, but such change was only
      significant in plasma. Biliary cirrhosis produces interesting changes in plasma
      and hepatic levels of cytokines and NO. This finding in chronic BDL model in rats
      has not been previously described in both tissues for such cytokines and NO.
      Cytokines and NO imbalance favor establishment and perpetuation of cirrhosis.

PMID- 16617008
TI  - T helper cell effector fates--who, how and where?
AB  - CD4 helper T cells functionally organize the host immune response by elaborating
      cytokines, often in patterns that have overlapping effects on other cells. Much
      interest centers on understanding how these stereotyped cytokine patterns become
      elaborated and what mechanisms underlie the generation of distinct helper T cell
      subsets. The past two years have seen advances in understanding of additional
      subsets, including T helper follicular cells and IL-17-producing T helper cells.
      Progress has also been achieved in resolving some of the crosstalk that regulates
      effector fate at the level of distinct transcription factors and chromatin
      reorganization of the cytokine genes, and a crucial role for gene silencing has
      been exposed. Finally, the role of innate cells in influencing these processes
      has become increasingly realized.

PMID- 16617009
TI  - A nine-year genetic survey of the causal agent of Dutch elm disease, Ophiostoma
      novo-ulmi in Winnipeg, Canada.
AB  - The causal agent of Dutch elm disease, Ophiostoma ulmi s. lat., has been
      spreading across North America since the 1920s. The population of the pathogen in
      Winnipeg, Manitoba, Canada was surveyed in 1993 and 2002 using a combination of
      RAPD marker analysis, vegetative compatibility tests, and surveys for viral
      double-stranded RNA (dsRNA). The data presented here show that the population,
      based on the vegetative compatibility and RAPD analysis, was highly genetically
      uniform, and has remained so for the nine-year duration of the study. The
      pathogen population was also monitored for the presence and spread of dsRNA
      molecules that, depending on identity, can be associated with a diseased
      phenotype and reduction of virulence in the pathogen. The current study found a
      very low incidence of dsRNA, and did not find any evidence for spread of these
      molecules through the population, even though there appeared to be no barriers to
      the transfer of the dsRNA between Winnipeg isolates. Despite the observation that
      isolates infected with the Winnipeg dsRNA showed no obvious phenotypic
      differences, the low incidence of dsRNA in general suggests that infected
      isolates do not compete as successfully as the uninfected isolates. The highly
      clonal nature of the pathogen population may be exploited in a control strategy.

PMID- 16617011
TI  - Telomerase regulation and stem cell behaviour.
AB  - Telomerase expression is restricted to a few cell types of the adult organism,
      most notably germ cells and stem/progenitor cells. Telomerase activity in germ
      cells is sufficient to prevent telomere shortening with age. Stem cells, however,
      do not have sufficient telomerase to prevent telomere shortening associated with
      continuous tissue renewal with increasing age. Indeed, telomerase levels in the
      adult organism are thought to be rate-limiting for longevity. This is supported
      by rare human syndromes caused by mutations in telomerase components, which are
      characterized by premature loss of tissue renewal and premature death. More
      recently, the role of telomerase and telomere length in stem cells is starting to
      be elucidated.

PMID- 16617012
TI  - Pilot installation for the thermo-chemical characterisation of solid wastes.
AB  - The increasing production and the large variety of wastes require operators of
      thermal treatment units to continuously adapt the installations or the
      functioning parameters to the different physical and chemical properties of the
      wastes. Usually, the treated waste is encountered in the form of heterogeneous
      mixtures. The classical tests such as thermogravimetry and calorimetric bomb
      operate component by component, separately. In addition to this, they can analyse
      only small quantities of waste at a time (a few grams). These common tests are
      necessary but insufficient in the global waste analysis in the view further
      thermal treatment. This paper presents an experimental installation, which was
      designed and built at the CNRS Science Division, Department of Industrial
      Methods, Compiegne University of Technology, France. It allows the determination
      of waste thermal and chemical properties by means of thermal treatment. Also, it
      is capable of continuously analysing significant quantities of waste (up to
      50kg/h) as compared to the classical tests and it can work under various
      conditions: The installation reproduces the process conditions from incinerators
      or pyrolysis reactors. It also provides complete information on the kinetics of
      the waste thermal degradation and on the pollutant emissions. Using different
      mixtures of components present in the municipal solid waste and also in the
      reconstituted MSW samples, we defined a series of criteria for characterising
      waste behaviour during the stages of the main treatment process such as: feeding,
      devolatilisation/oxidation, advancement, solid residue evacuation, and pollutants
      emission.

PMID- 16617013
TI  - Molecular regulation of an invasion-related molecule--options for tumour staging
      and clinical strategies.
AB  - This review provides a summary of the European Association for Cancer Research
      Award Lecture, presented at the ECCO13 meeting in Paris in November 2005. It is a
      brief overview on the biological and clinical relevance of the urokinase receptor
      (u-PAR), an essential molecule to promote invasive and metastatic tumour
      phenotype and shown to be associated with early relapse and poor prognosis in
      many different types of cancers. The review summarizes the most important
      transcriptional mechanisms regulating u-PAR gene, and will focus on the
      differential binding of transcription factors to u-PAR promoter elements from
      studies in resected tumour and normal tissues of colorectal and gastric cancer
      patients. These studies conducted by our group may help to understand
      transcriptional mechanisms, which are employed to promote invasion and
      metastasis, in subpopulations of cancer patients. Such studies could lead to a
      more target-oriented patient selection and therapy against transcriptional and
      oncogeneic regulators in cancer.

PMID- 16617014
TI  - Association of SULT2A1 allelic variants with plasma adrenal androgens and
      prostate cancer in African American men.
AB  - Dehydroepiandrosterone (DHEA) sulfate which is present at micromolar levels in
      the plasma, can be desulfated to supply free DHEA for metabolism to androgens or
      estrogens in peripheral tissues. Human cytosolic sulfotransferase (SULT) 2A1
      catalyzes DHEA sulfation in the adrenal cortex. Three SULT2A1 nonsynonymous
      coding single nucleotide polymorphisms (SNPs), identified only in African
      Americans (AA), are associated with decreased levels of activity and expression
      as compared to wild-type cDNA when expressed in COS cells. To test whether the
      SNPs are associated with decreased plasma androgens, 124 normal AA men were
      genotyped and plasma DHEA, DHEA-sulfate and testosterone levels determined. The
      two SNPs identified in these participants occurred at allelic frequencies of
      0.044 (G187C) and 0.101 (G781A). The G187C SNP was highly linked to the G781A
      SNP. Although no differences in hormone levels were associated with the
      individual SNPs, a significant increase in the DHEA:DHEA-sulfate ratio was
      observed in participants with a heterozygous G187C/G781A genotype. Increased free
      DHEA levels may result in increased testosterone synthesis and stimulation in the
      prostate, therefore a group of AA prostate cancer (PC) patients and controls were
      genotyped. No significant association of the presence of the different SULT2A1
      alleles with the occurrence of PC was detected.

PMID- 16617015
TI  - Application of thermoalkalophilic xylanase from Arthrobacter sp. MTCC 5214 in
      biobleaching of kraft pulp.
AB  - A thermoalkalophilic and cellulase-free xylanase produced from Arthrobacter sp.
      MTCC 5214 by solid-state fermentation using wheat bran as a carbon source was
      evaluated for prebleaching of kraft pulp. The UV absorption spectrum of the
      compounds released by enzyme treatment showed a characteristic peak at 280 nm,
      indicating the presence of lignin in the released colouring matter. Enzymatic
      prebleaching of kraft pulp showed 20% reduction in kappa number of the pulp
      without much change in viscosity. Enzymatic treatment reduced the amount of
      chlorine by 29% without any decrease in brightness. The viscosity of xylanase
      treated pulp was 4.0 p, whereas the viscosity of the pulp treated exclusively
      with chlorine was 4.1 p.

PMID- 16617016
TI  - 3,4-Fused cyclohexyl sulfones as gamma-secretase inhibitors.
AB  - The 3,4-fused sulfamides, sulfonamides and sulfone have been identified as highly
      potent gamma-secretase inhibitors. Evaluation of the SAR of substitution within
      these series has allowed the identification of a range of compounds which
      significantly reduce brain A beta in transgenic mouse models and thus have
      potential as possible treatments for Alzheimer's disease.

PMID- 16617017
TI  - Design, synthesis, and evaluation of novel kazusamycin A derivatives as potent
      antitumor agents.
AB  - Novel kazusamycin A derivatives were designed in the viewpoint of decrease of
      reactivity at the alpha,beta-unsaturated delta-lactone moiety against Michael
      type addition. Although 25-30 steps were required for the synthesis of each
      compound, their syntheses were achieved. Cytotoxicity against HPAC cell line was
      evaluated, and two of them exhibited comparable potency to kazusamycin A. Hepatic
      toxicity of these designed compounds was much lower than that of kazusamycin A.

PMID- 16617018
TI  - Diphenylmethane skeleton as a multi-template for nuclear receptor ligands:
      preparation of FXR and PPAR ligands.
AB  - Novel, potent farnesoid X receptor (FXR) and peroxisome proliferator-activated
      receptor alpha (PPARalpha) agonists were obtained by using a diphenylmethane
      skeleton as a substitute for a steroid skeleton.

PMID- 16617019
TI  - Learning from experience: constructing critical case reviews for a leadership
      programme.
AB  - A previous paper described the development of a leadership programme for critical
      care and highlighted that one of the strengths of the programme was the critical
      case review. This paper sets out in some depth the major theoretical influences
      in the construction of the case review. Case reviews have been used in education
      for some time but often have predetermined outcomes. The education approach
      favoured here was based on action learning, which in itself belongs to the broad
      church of reflective practice. While reflective practice has been advocated in
      nursing since 1986 together with the introduction of clinical supervision neither
      have met with unqualified success in their own right. This paper concludes that
      while the concept and construction of the critical case review may be new it is
      in essence no more than a jigsaw of already well-established practices of
      reflection, clinical supervision and action learning woven into the foundations
      of clinical risk management and whole systems working.

PMID- 16617020
TI  - The synthesis and anti-proliferative effects of beta-elemene derivatives with
      mTOR inhibition activity.
AB  - Fourteen beta-elemene derivatives containing a piperazine, a morpholine, a
      tetrahydropyrrole, a thiophenylethylamine, or a cyclohexamine group were
      synthesized. The structures of these beta-elemene derivatives were characterized
      with IR, 1H NMR, MS, and elemental analyses. All these derivatives had an
      increased anti-proliferative activity in human cervix epitheloid carcinoma HeLa,
      gastric carcinoma SGC-7901, and leukemia K562 cells comparing with that of beta
      elemene. Among these derivatives, 13,14-bis(cis-3,5-dimethyl-1-piperazinyl)-beta
      elemene (IIi), 13,14-bis[2-(2-thiophenyl)ethylamino]-beta-elemene (IIm), and
      13,14-bis(cyclohexamino)-beta-elemene (IIn) were the most potent agents. IIi,
      IIm, and IIn inhibited K562 cell growth with an IG50 below 5 microM that was
      correlated with mTOR activity inhibition.

PMID- 16617021
TI  - Study of the disassembly-assembly process of alpha-synuclein fibrils by in situ
      atomic force microscopy.
AB  - In this report, we applied in situ atomic force microscopy (AFM) to study the
      dynamic process of disassembly-assembly of alpha-synuclein (alpha-Syn) fibrils in
      different solutions. Most of the mica-adsorbed alpha-Syn fibrils disassemble into
      small particles step-by-step on the mica surface in diluted solutions, yet a few
      short fibrils still extend to form longer fibrils. This process usually started
      randomly at the center of the long fibrils, which progressively disassemble into
      short fragments and small protein particles of varying size. Compared to
      disassembly, assembly happened infrequently when the protein concentration was
      low. It was observed directly by AFM that the chaotropic agent guanidinium
      chloride rapidly breaks the long alpha-Syn fibrils.

PMID- 16617022
TI  - Synthesis and evaluation of fluorine-18 labelled compounds for imaging of
      bacterial infections with pet.
AB  - Syntheses of no carrier added (n.c.a.) 6-fluoro-1,4-dihydro-1-cyclopropyl-4-oxo-7
      [4-[18F]fluoro-phenacyl-1-piperacinyl]-chinolincarboxylic acid ([18F]COPCA) and
      n.c.a. 4-[18F]fluoro-benzoyl-ubiquicidin 29-41 ([18F]UBI 29-41) are described.
      [18F]COPCA was synthesised within 120 min with a radiochemical yield of 9-12%.
      [18F]UBI 29-41 was synthesised within 150 min with a radiochemical yield of 15
      20%. Both compounds had a specific activity of more than 35 GBq/micromol. The
      biological activity was verified by measuring its binding to Staphylococcus
      aureus bacteria. Specific binding was found for [18F]UBI 29-41 (12-17%), whereas
      no specific binding for [18F]COPCA was found.

PMID- 16617023
TI  - Production of [15O]water at low-energy proton cyclotrons.
AB  - We report a simple system for producing [15O]H2O from 15N in a nitrogen/hydrogen
      gas target with recycling of the target nitrogen, allowing production on low
      energy proton-only accelerators with minimal consumption of isotopically enriched
      15N. The radiolabeled water is separated from the target gas and radiolytically
      produced ammonia by temporary freezing in a small trap at -40 degrees C.

PMID- 16617024
TI  - Mitochondrial DNA evidence of an early Holocene population expansion of
      threespine sticklebacks from Scotland.
AB  - In this study, we analyzed the cytochrome b gene in threespine stickleback
      (Gasterosteus aculeatus) populations from Scotland. We found evidence of a
      postglacial population expansion in Scotland and large differences in genetic
      diversity estimates among populations. Higher levels of genetic diversity are
      negatively correlated with distance from the ocean. In addition, distance from
      the ocean and predation risk both explain variation in plate count in Scottish
      populations. Overall, the mtDNA data support the racemic model of evolution in
      threespine stickleback.

PMID- 16617025
TI  - The pathophysiological mechanisms of cognitive and behavioral disturbances in
      children with Landau-Kleffner syndrome or epilepsy with continuous spike-and
      waves during slow-wave sleep.
AB  - Epilepsy with continuous spike- and -waves during slow-wave sleep and Landau
      Kleffner syndrome are two rare childhood epilepsy syndromes. The underlying
      pathophysiology remains unknown. The current opinions about epidemiologic risk
      factors, genetic predisposition, EEG and MEG findings, influence of anti
      epileptic drugs, neuroradiology, positron emission tomopgraphy, evoked
      potentials, auto-immunity and subpial transection are summarized.

PMID- 16617026
TI  - Biochemical effects of two different hyaluronic acid products in a co-culture
      model of osteoarthritis.
AB  - OBJECTIVES: To compare the effects of two hyaluronic acid (HA) formulations on
      mediators of matrix turnover and inflammation in an IL-1-treated cartilage
      synovium co-culture model with the aim of elucidating mechanisms by which
      viscosupplementation exerts beneficial effects in osteoarthritic joints. DESIGN:
      A co-culture model (100 ng/ml interleukin-1beta (IL-1beta) added to canine
      synovial and cartilage explants) was used to investigate the effects of HA on
      cartilage-synovium interactions. Three concentrations (1x, 0.5x, and 0.1x) of two
      commercial sources of HA (A: Synvisc [hylan G-F 20]; B: Hyalgan [sodium
      hyaluronate]) were used. Co-cultures without IL-1beta (negative) or with IL-1beta
      (positive) but neither HA product served as controls. The liquid media were
      collected every 3 days and explants of cartilage and synovium were collected on
      days 3, 6, and 20. Media and explants were analyzed histologically,
      biochemically, and immunohistochemically. RESULTS: Glycosaminoglycan (GAG)
      content was measured in cartilage explants. GAG content in explants was higher in
      both HA groups at the beginning and the conclusion of the study compared to the
      IL-1beta-treated group. GAG content of the media was significantly (P<0.05) lower
      in the Synvisc group than all other groups early. The Hyalgan group demonstrated
      progressively less GAG release later in the study. The addition of Synvisc did
      not decrease the matrix metalloproteinase (MMP)-3 concentrations at any point.
      MMP-3 concentrations were significantly (P<0.05) lower among the 1x and 0.5x
      Hyalgan groups on day 20 compared to the IL-1beta-treated group. On day 3,
      prostaglandin E(2) concentrations were significantly (P<0.05) higher in the IL
      1beta-treated group compared to other groups. Both HA groups had less nitric
      oxide production than the control groups throughout the study. CONCLUSIONS: This
      study supports two potential mechanisms for viscosupplementation: a biosynthetic
      chondroprotective mechanism, with a possible delay in onset depending on the form
      of HA; and an anti-inflammatory mechanism.

PMID- 16617027
TI  - Perirhinal cortex lesions impair feature-negative discrimination.
AB  - The role of the perirhinal cortex in inhibitory eyeblink conditioning was
      examined. In Experiment 1, rats were given lesions of the perirhinal cortex or
      control surgery and subsequently trained with a feature-negative discrimination
      procedure followed by summation and retardation tests for conditioned inhibition.
      Perirhinal cortex lesions impaired, but did not prevent acquisition of feature
      negative discrimination. Results from the summation test showed that rats with
      perirhinal cortex lesions could not generalize feature-negative discrimination to
      a new stimulus. There were no group differences during the retardation test.
      Experiment 2 showed that lesions of the perirhinal cortex did not impair simple
      excitatory conditioning. Experiment 3 showed that perirhinal cortex lesions had
      no effect on acquisition of a simple tone-light discrimination. The results
      suggest that the perirhinal cortex plays a role in eyeblink conditioning when
      using discrimination procedures involving overlapping stimuli.

PMID- 16617028
TI  - Comparison of carbon-impregnated and standard ePTFE prostheses in extra
      anatomical anterior tibial artery bypass: a prospective randomized multicenter
      study.
AB  - OBJECTIVES: The aim of this study was to find out whether carbon impregnated
      ePTFE vascular grafts have better long-term patency or limb salvage rates than
      Standard ePTFE vascular grafts in crural revascularization in patients with
      chronic critical ischemia. DESIGN: Prospective randomized multicenter trial.
      Study endpoints were 36 months follow-up, major amputation or death. MATERIALS:
      We used 6mm carbon ePTFE (Carboflo) and 6mm standard ePTFE vascular grafts (both
      C.R. BARD Inc./IMPRA). METHODS: From June 1995 to November 1998, 283 patients
      were randomly assigned either to carbon (C) (n=140) or to standard (St) ePTFE
      (n=143) vascular grafts at 19 centres. A standard protocol was used with lateral
      extra-anatomic course of the graft to the anterior tibial artery and of a distal
      vein patch or cuff. More than 90% of the patients had rest pain or gangrene.
      RESULTS: Two hundred and sixty-five (C=130; St=135) patients could be analysed in
      the intention-to-treat (ITT) group. Primary patency, secondary patency and limb
      salvage rates after 36 months were 33, 43 and 67% in the carbon- and 30, 38 and
      58% in the standard PTFE group, respectively, (log-rank test: p=0.20, 0.12 and
      0.16). Additional analyses were made per protocol (PP) and as-treated (AT). The
      retrospective power of the study was calculated as 79 and 83%. CONCLUSION: The
      ITT, PP and AT analysis, showed no statistically significant advantage of the
      carbon ePTFE vascular graft in terms of patency or limb salvage over the standard
      ePTFE vascular graft at 36 months.

PMID- 16617029
TI  - Attention deficit disorders: are we barking up the wrong tree?
AB  - Attention deficit disorder (AAD) and attention deficit/hyperactivity disorder
      (ADHD) are very frequent and protean developmental disorders without a definite
      biologic marker. This review proposes a framework to understand the enlarged
      spectrum of its manifestations based on current knowledge of the mechanisms
      underlying arousal and attention variations during sleep/wake cycle. The neuro
      modulation's pivotal role in this process as well as in the fine tuning of
      synaptic architecture during development must be taken into account when trying
      to understand the marked fuzziness of the symptoms and the very high prevalence
      of reported co-morbidities. The series of related interactions includes a cyclic
      deactivation of the dorso-lateral portion of the prefrontal cortex (DLPFC) during
      sleep, suspending executive functions, co-occurring with rhythmic periods of
      decreased noradrenergic tonus. A protracted unbalance in modulation, with
      catecholaminergic relative deficiency, could explain less-than-optimum waking
      DLPFC activation and the most important manifestations of ADD. Beside the well
      documented dopaminergic effects of stimulant medication used in ADD and ADHD, a
      more important role must be assigned to noradrenaline (NA). At this light
      hyperactivity and impulsivity are less important dimensions. Rather, an attention
      deficit spectrum disorder should probably be regarded as a complication of a core
      defect in prefrontal cortex dependent inhibitory control, underlying inattention.

PMID- 16617030
TI  - Fast amplitude-modulated pulse trains with frequency sweep (SW-FAM) in static NMR
      of half-integer spin quadrupolar nuclei.
AB  - In solid-state NMR of quadrupolar nuclei with half-integer spin I, fast amplitude
      modulated (FAM) pulse trains have been utilised to enhance the intensity of the
      central-transition signal, by transferring spin population from the satellite
      transitions. In this paper, the signal-enhancement performance of the recently
      introduced SW-FAM pulse train with swept modulation frequency [T. Brauniger, K.
      Ramaswamy, P.K. Madhu, Enhancement of the central-transition signal in static and
      magic-angle-spinning NMR of quadrupolar nuclei by frequency-swept fast amplitude
      modulated pulses, Chem. Phys. Lett. 383 (2004) 403-410] is explored in more
      detail for static spectra. It is shown that by sweeping the modulation
      frequencies linearly over the pulse pairs (SW1/tau-FAM), the shape of the
      frequency distribution is improved in comparison to the original pulse scheme
      (SWtau-FAM). For static spectra of 27Al (I=5/2), better signal-enhancement
      performance is found for the SW1/tau-FAM sequence, as demonstrated both by
      experiments and numerical simulations.

PMID- 16617031
TI  - Effect of alendronate on bone mineral density in adult patients with Laron
      syndrome (primary growth hormone insensitivity).
AB  - Severe short stature resulting from a deficiency in insulin-like growth factor-I
      (IGF-I) is a prominent feature of Laron syndrome (LS). Whether patients with LS
      are osteopenic or not, and whether they need treatment with bisphosphonates,
      remains uncertain. The aim of this study was to investigate the action of
      alendronate on the IGF-I-deficient bones of adult patients with LS and
      osteoporosis, as determined by dual X-ray absorptiometry . Seven patients (5
      women and 2 men) of mean age 40.8+/-7.6 years and mean bone mass density (BMD)
      0.843+/-0.06 g/cm2 (T score -2.9+/-0.5) at the lumbar spine and 0.734+/-0.11
      g/cm2 (T score -2.2+/-0.9) at the femoral neck were treated with alendronate 70
      mg once/weekly over a 12-month period. Treatment led to an increase of 5.3% in
      BMD (p=0.038) at the femoral neck. There was a similar trend at the lumbar spine,
      but the difference was not statistically significant (2.3%, p=0.34). Mean total
      alkaline phosphatase decreased by 14% from normal range at baseline (p=0.007).
      Urinary deoxypyridinoline levels, which were elevated at baseline (10+/-2.3
      nM/mMcre), showed a nonsignificant change during treatment. Our study suggests
      that treatment with alendronate may have positive effects in patients with LS and
      low BMD on dual X-ray absorptiometry.

PMID- 16617032
TI  - Believe it or not, QTLs are accurate!
AB  - It is generally believed that mapping quantitative trait loci (QTLs) does not
      accurately position genes underlying polygenic traits on the genome, which limits
      the application of QTL analysis in marker-assisted selection and gene discovery.
      However, now that a few plant QTLs have been cloned or accurately tagged, it
      appears that they might be accurate to within 2cM or less. This means that there
      will be circumstances when map-based cloning using only original mapping data
      would be a realistic option that avoids time-consuming and expensive fine
      mapping. Acceptance of this view would enhance the value of past and future
      mapping experiments, particularly those revealing small and environmentally
      sensitive QTLs that are often considered intractable at the molecular level.

PMID- 16617033
TI  - Physiology and metabolism: the second coming of plant biochemistry and
      physiology.

PMID- 16617034
TI  - Metabolic engineering of Escherichia coli and Corynebacterium glutamicum for
      biotechnological production of organic acids and amino acids.
AB  - Industrial microorganisms have been developed as biocatalysts to provide new or
      to optimize existing processes for the biotechnological production of chemicals
      from renewable plant biomass. Rational strain development by metabolic
      engineering is crucial to successful processes, and is based on efficient genetic
      tools and detailed knowledge of metabolic pathways and their regulation. This
      review summarizes recent advances in metabolic engineering of the industrial
      model bacteria Escherichia coli and Corynebacterium glutamicum that led to
      efficient recombinant biocatalysts for the production of acetate, pyruvate,
      ethanol, d- and l-lactate, succinate, l-lysine and l-serine.

PMID- 16617035
TI  - Status of clinical gene sequencing data reporting and associated risks for
      information loss.
AB  - Clinical gene sequencing is growing in importance and cost-effectiveness. In the
      past two years, the number of genes associated with disease has grown by roughly
      25%. Knowledge of genetic variations will soon guide drug selection and dosages,
      predict risks from toxin exposures, and inform nutritional needs. Despite the
      significance of sequencing, methods for reporting results are problematic.
      Frequent use of paper and infrequent use of naming standards impede data exchange
      and make incorporation into the electronic medical record difficult. Reports
      often describe only variations found, rather than all data (all patient bases
      sequenced). Also, reports frequently do not describe reference data used to
      define variations. These practices create risks for loss of both data and
      information. Standardized electronic reporting of all data (all bases sequenced
      and all reference data) and electronic record systems capable of storing these
      results would both prevent data loss and simplify the preservation of information
      those data provide.

PMID- 16617036
TI  - Screening for basic drugs in equine urine using direct-injection differential
      gradient LC-LC coupled to hybrid tandem MS/MS.
AB  - A rapid, selective and robust direct-injection LC/hybrid tandem MS method has
      been developed for simultaneous screening of more than 250 basic drugs in the
      supernatant of enzyme hydrolysed equine urine. Analytes, trapped using a short
      HLB extraction column, are refocused and separated on a Sunfire C(18) analytical
      column using a controlled differential gradient generated by proportional
      dilution of the first column's eluent with water. Independent data acquisition
      (IDA) was configured to trigger a sensitive enhanced product ion (EPI) scan when
      a multiple reaction monitoring (MRM) survey scan signal exceeded the defined
      criteria. The decision on whether or not to report a sample as a positive result
      was based upon both the presence of a MRM response within the correct retention
      time range and a qualitative match between the EPI spectrum obtained and the
      corresponding reference standard. Ninety seven percent of the drugs targeted by
      this method met our detection criteria when spiked into urine at 100 ng/ml; 199
      were found at 10 ng/ml, 83 at 1 ng/ml and 4 at 0.1 ng/ml.

PMID- 16617037
TI  - A demonstration of the use of ultra-performance liquid chromatography-mass
      spectrometry [UPLC/MS] in the determination of amphetamine-type substances and
      ketamine for forensic and toxicological analysis.
AB  - We have recently seen the emergence of ultra-performance liquid chromatography
      (UPLC) coupled to mass spectrometry as an alternative to traditional high
      performance liquid chromatography techniques. The strengths of UPLC technology
      promote the ability to separate and identify drug compounds with significant
      gains in resolution and sensitivity and marked reductions in the overall time of
      analysis. As increased throughput is the desire of the practical toxicology
      laboratory, the aim of this study was to trial commercially available technology
      by assessment of the separation of several commonly encountered amphetamine-type
      substances. From injection of a poly-drug reference standard and whole blood
      extract, we successfully separated and identified amphetamine, methamphetamine,
      ephedrine, pseudoephedrine, phentermine, MDA, MDMA, MDEA and ketamine in less
      than 3 min using the Acquity UPLC-Micromass Quattro Micro API MS instrumentation
      (Waters Corporation, USA). In addition to this significant reduction in overall
      run time, all peaks exhibited acceptable resolution using selected ion recording
      (SIR), with analysis indicating the capability to separate 5-11 peaks in 1.75 min
      using the current system parameters. From this introductory data, it is therefore
      indicated that the technological advancements defining ultra-performance liquid
      chromatography will allow it to serve as a powerful analytical tool for rapid
      throughput analysis.

PMID- 16617038
TI  - Fast simultaneous determination of urinary 1-hydroxypyrene and 3
      hydroxybenzo[a]pyrene by liquid chromatography-tandem mass spectrometry.
AB  - A fast analysis method using liquid chromatography-atmospheric pressure chemical
      ionization tandem mass spectrometry was developed for the simultaneous
      determination of the 1-hydroxypyrene (1-OHP) and 3-hydroxybenzo[a]pyrene (3
      OHBaP) in urine. Mass transitions were monitored at m/z 219.3-200.0 for 1-OHP and
      m/z 269.2-252.2 for 3-OHBaP. Only 10 min was needed for the analysis. The
      recovery was 60% for 3-OHBaP and 91% for 1-OHP, respectively. And the method
      detection limits were 0.49 microg/L for 1-OHP and 1.03 microg/L for 3-OHBaP. The
      inter- and intra-day relative standard deviations were in the range of 2.8-8.9%
      for 1-OHP and 9.7-20.8% for 3-OHBaP, respectively. The developed method was
      successfully used to measure urinary PAH metabolites of student volunteers in a
      high school.

PMID- 16617039
TI  - Parathyroid hormone 1-34 enhances titanium implant anchorage in low-density
      trabecular bone: a correlative micro-computed tomographic and biomechanical
      analysis.
AB  - The use of endosseous titanium implants is the standard of care in dentistry and
      orthopaedic surgery. Nevertheless, implantation in low-density bone has a poor
      prognosis and experimental studies show delayed implant anchorage following
      gonadectomy-induced bone loss. Intermittently administered human parathyroid
      hormone 1-34 [iahPTH(1-34)] is the leading bone anabolic therapy. Hence, this
      study assessed whether iahPTH(1-34) enhances titanium implant integration in low
      density bone. Threaded titanium implants, 0.9 mm in diameter, were inserted
      horizontally into the proximal tibial metaphysis of 5-month-old rats, 7 weeks
      postorchiectomy (ORX). Subcutaneous administration of iahPTH(1-34), at 5, 25 and
      75 microg/kg/day commenced immediately thereafter and lasted for 8 weeks.
      Quantitative micro-computed tomography (muCT) at the implantation site was
      carried out at 15 microm resolution using high energy and long integration time
      to minimize artifacts resulting from the high implant radiopacity.
      Osseointegration (OI) was calculated as percent implant surface in contact with
      bone (%OI) quantified as the ratio of "bone"-to-total voxels in contact with the
      implant. Additionally, the trabecular bone volume density (BV/TV), trabecular
      thickness (Tb.Th), trabecular number (Tb.N) and connectivity density (Conn.D)
      were measured in the peri-implant bone. All microCT parameters were stimulated by
      iahPTH(1-34) dose-dependently; the percent maximal enhancement was %OI = 143,
      BV/TV = 257, Tb.Th = 150, Tb.N = 140 and Conn.D = 193. The maximal values of %OI,
      BV/TV and Tb.Th in iahPTH(1-34)-treated ORX rats exceeded significantly those
      measured in the implantation site of untreated sham-ORX controls. The same
      specimens were then subjected to pullout biomechanical testing. The biomechanical
      parameters were also enhanced by iahPTH(1-34) dose-dependently, exceeding the
      values recorded in the sham-ORX controls. The percent iahPTH(1-34)-induced
      maximal enhancement was: ultimate force = 315, stiffness = 270 and toughness =
      395. Except for the BV/TV and Tb.Th, there was no significant difference between
      the effect of the 25 and 75 microg/kg/day doses. There was a highly significant
      correlation between the morphometric and biomechanical parameters suggesting the
      use of quantitative CT as predictive of the implant mechanical properties. These
      findings demonstrate that iahPTH(1-34) effectively stimulates implant anchorage
      in low-density trabecular bone and thus the feasibility of administering iahPTH(1
      34) to improve the clinical prognosis in low-density trabecular bone sites.

PMID- 16617040
TI  - Descriptive analysis of the results of an anonymous postal survey of the
      occurrence of scrapie in Great Britain in 2002.
AB  - An anonymous postal survey was conducted in 2002 to estimate the proportion of
      farms in Great Britain affected with scrapie and to gather information on the
      likely risk factors for the occurrence of the disease; the response rate was 53
      per cent. The survey showed that 1 per cent of the respondents thought they had
      had scrapie in their flock in the previous 12 months, and that 12 per cent
      thought they had had scrapie in the past. The results of the survey were
      consistent with the results of a similar survey carried out in 1998, and with
      notification patterns, but in 1998 approximately 3 per cent of farmers reported
      having had scrapie in the previous 12 months. It is not clear whether the
      apparent decrease in the prevalence of scrapie is real or whether it may be due
      to factors such as sampling biases, or to the increasing knowledge of the signs
      of scrapie shown by the respondents in 2002.

PMID- 16617041
TI  - Development and Bayesian evaluation of an ELISA to detect specific antibodies to
      Sarcoptes scabiei var suis in the meat juice of pigs.
AB  - Samples of ear scrapings, serum and diaphragmatic muscle were collected from 271
      fattening pigs at the slaughterhouse. The scrapings were examined for the
      presence of mites, and tests for specific antibodies to Sarcoptes scabiei var
      suis in the serum and meat juice were made with an experimental ELISA. The cut
      off value for the meat-juice ELISA was estimated at an optical density of 0.5 by
      receiver operating characteristic curve analysis, on the basis of the cut-off
      value for the serum ELISA of 0.4. The results of the three tests were used in a
      Bayesian model to estimate the characteristics of each test. The specificity of
      the tests of the ear scrapings was considered to be 1 and their sensitivity was
      estimated by Bayesian analysis to be 0.86, with a 95 per cent confidence interval
      (CI) of 0.73 to 0.99. The sensitivity of the meat juice ELISA (0.71, 95 per cent
      CI 0.6 to 0.8) and its specificity (0.77, 95 per cent CI 0.66 to 0.89) were
      comparable with the sensitivity (0.73, 95 per cent CI 0.6 to 0.8) and specificity
      (0.81, 95 per cent CI 0.69 to 0.95) of the serum ELISA.

PMID- 16617042
TI  - Investigations of the potential risk factors associated with cases of bovine
      spongiform encephalopathy in Bavaria, Germany.
AB  - In order to identify the management and feeding practices that might have
      contributed to the occurrence of bovine spongiform encephalopathy (BSE) in
      Bavaria, Germany, information from 110 dairy farms on which a case of BSE had
      been reported was compared with information derived from a questionnaire sent to
      approximately 10,000 Bavarian farms on which no case of BSE had been reported up
      to February 2003. Representative information was obtained from 4006 dairy farms.
      The results indicated that in comparison with these control farms a higher
      proportion of the BSE farms had also kept pigs or poultry, although the
      difference was not significant, and that a significantly higher proportion of the
      BSE farms had fed proprietary concentrates and/or milk replacers to their calves.

PMID- 16617043
TI  - Neuromuscular disease associated with glycogen storage in a Spanish-bred filly.

PMID- 16617044
TI  - Polioencephalomalacia in a juvenile hooded seal (Cystophora cristata).

PMID- 16617045
TI  - Congenital holoprosencephaly with severe otocephaly in a rottweiler puppy.

PMID- 16617046
TI  - Provisions for emergency slaughter of cattle.

PMID- 16617047
TI  - Ulcerative foot condition in dogs.

PMID- 16617048
TI  - Detection of feline infectious peritonitis virus-like antigen in ferrets.

PMID- 16617050
TI  - Farm health planning in Wales.

PMID- 16617051
TI  - Conservative Veterinary Society.

PMID- 16617053
TI  - TB policy and the badger culling trials.

PMID- 16617054
TI  - Differential interactions between transforming growth factor-beta3/TbetaR1, TAB1,
      and CD2AP disrupt blood-testis barrier and Sertoli-germ cell adhesion.
AB  - The biochemical basis that regulates the timely and selective opening of the
      blood-testis barrier (BTB) to migrating preleptotene/leptotene spermatocytes at
      stage VIII of the epithelial cycle in adult rat testes is virtually unknown.
      Recent studies have shown that cytokines (e.g. transforming growth factor (TGF)
      beta3) may play a crucial role in this event. However, much of this information
      relies on the use of toxicants (e.g. CdCl(2)), making it difficult to relay these
      findings to normal testicular physiology. Here we report that overexpression of
      TGF-beta3 in primary Sertoli cells cultured in vitro indeed perturbed the tight
      junction (TJ) barrier with a concomitant decline in the production of BTB
      constituent proteins as follows: occludin, N-cadherin, and ZO-1. Additionally,
      local administration of TGF-beta3 to testes in vivo was shown to reversibly
      perturb the BTB integrity and Sertoli-germ cell adhesion via the p38 MAPK and ERK
      signaling pathways. Most importantly, the simultaneous activation of p38 and ERK
      signaling pathways is dependent on the association of the TGF-beta3-TbetaR1
      complex with adaptors TAB1 and CD2AP because if TbetaR1 was associated
      preferentially with CD2AP, only Sertoli-germ cell adhesion was perturbed without
      compromising the BTB. Collectively, these data illustrate that local production
      of TGF-beta3, and perhaps other TGF-betas and cytokines, by Sertoli and germ
      cells into the microenvironment at the BTB during spermatogenesis transiently
      perturbs the BTB and Sertoli-germ cell adhesion to facilitate germ cell migration
      when the activated TbetaRI interacts with adaptors TAB1 and CD2AP. However, TGF
      beta3 selectively disrupts Sertoli-germ cell adhesion in the seminiferous
      epithelium to facilitate germ cell migration without compromising BTB when
      TbetaRI interacts only with adaptor CD2AP.

PMID- 16617055
TI  - Sumoylation delimits KLF8 transcriptional activity associated with the cell cycle
      regulation.
AB  - KLF8 (Kruppel-like factor 8) is a member of the Kruppel transcription factor
      family that binds CACCC elements in DNA and activates or represses their target
      genes in a context-dependent manner. Here we present sumoylation as a novel
      mechanism that regulates KLF8 post-translationally. We found that KLF8 can be
      covalently modified by small ubiqitin-like modifier (SUMO)-1, SUMO-2, and SUMO-3
      in vivo. We showed that KLF8 interacted with the PIAS family of SUMO E3 ligases
      PIAS1, PIASy, and PIASxalpha but not with E2 SUMO-conjugating enzyme Ubc9.
      Furthermore, we demonstrated that the E2 and E3 ligases enhanced the sumoylation
      of KLF8. In addition, site-directed mutagenesis identified lysine 67 as the major
      sumoylation site on KLF8. Lysine 67 to arginine mutation strongly enhanced
      activity of KLF8 as a repressor or activator to its physiological target
      promoters and as an inducer of the G(1) cell cycle progression. Taken together,
      our results demonstrated that sumoylation of KLF8 negatively regulates its
      transcriptional activity and cellular functions.

PMID- 16617056
TI  - Caspase-2 triggers Bax-Bak-dependent and -independent cell death in colon cancer
      cells treated with resveratrol.
AB  - Polyphenol phytoalexin (resveratrol), found in grapes and red wine is a strong
      chemopreventive agent with promising safety records with human consumption and
      unique forms of cell death induction in a variety of tumor cells. However, the
      mechanism of resveratrol-induced apoptosis upstream of mitochondria is still not
      defined. The results from this study suggest that caspase-2 activation occurs
      upstream of mitochondria in resveratrol-treated cells. The upstream activation of
      caspase-2 is not dependent on its antioxidant property or NF-kappaB inhibition.
      The activated caspase-2 triggers mitochondrial apoptotic events by inducing
      conformational changes in Bax/Bak with subsequent release of cytochrome c,
      apoptosis-inducing factor, and endonuclease G. Caspase-8 activation seems to be
      independent of these events and does not appear to be mediated by classical death
      receptor processing or downstream caspases. Both caspase-2 and caspase-8
      contribute toward the mitochondrial translocation of Bid, since neither caspase-8
      inhibition nor caspase-2 inhibition could prevent translocation of Bid DsRed into
      mitochondria. Caspase-2 inhibitors or antisense silencing of caspase-2 prevented
      cell death induced by resveratrol and partially prevented processing of
      downstream caspases, including caspase-9, caspase-3, and caspase-8. Studies using
      mouse embryonic fibroblasts deficient for both Bax and Bak indicate the
      contribution of both Bax and Bak in mediating cell death induced by resveratrol
      and the existence of Bax/Bak-independent cell death possibly through caspase-8-
      or caspase-2-mediated mitochondria-independent downstream caspase processing.

PMID- 16617057
TI  - Depletion of hsp90beta induces multiple defects in B cell receptor signaling.
AB  - Hsp90 participates in many distinct aspects of cellular functions and
      accomplishes these roles by interacting with multiple client proteins. To gain
      insight into the interactions between Hsp90 and its clients, here we have reduced
      the protein level of Hsp90 in avian cells by gene targeting in an attempt to
      elicit the otherwise undetectable (because of the vast amount of cellular Hsp90)
      Hsp90-interacting proteins. Hsp90beta-deficient cells can grow, albeit more
      slowly than wild-type cells. B cell antigen receptor signaling is multiply
      impaired in these mutant cells; in particular, the amount of immunoglobulin M
      heavy chain protein is markedly reduced. Furthermore, serum activation does not
      promote ERK phosphorylation in Hsp90beta-deficient cells. These multifaceted
      depressive effects seem to be provoked independently of each other and possibly
      recapitulate the proteome-wide in vivo functions of Hsp90. Reintroduction of the
      Hsp90beta gene efficiently restores all of the defects. Unexpectedly, however,
      introducing the Hsp90alpha gene is also effective in restoration; thus, these
      defects might be caused by a reduction in the total expression of Hsp90 rather
      than by loss of Hsp90beta-specific function.

PMID- 16617058
TI  - Pseudomonas aeruginosa porin OprF: properties of the channel.
AB  - Using ion channel reconstitution in planar lipid bilayers, we examined the
      channel-forming activity of subfractions of Pseudomonas aeruginosa OprF, which
      was shown to exist in two different conformations: a minority single domain
      conformer and a majority two-domain conformer (Sugawara, E., Nestorovich, E. M.,
      Bezrukov, S. M., and Nikaido, H. (2006) J. Biol. Chem. 281, 16220-16229). With
      the fraction depleted for the single domain conformer, we were unable to detect
      formation of any channels with well defined conductance levels. With the
      unfractionated OprF, we saw only rare channel formation. However, with the single
      domain-enriched fraction of OprF, we observed regular insertion of channels with
      highly reproducible conductances. Single OprF channels demonstrate rich kinetic
      behavior exhibiting spontaneous transitions between several subconformations that
      differ in ionic conductance and radius measured in polymer exclusion experiments.
      Although we showed that the effective radius of the most conductive conformation
      exceeds that of the general outer membrane porin of Escherichia coli, OmpF, we
      also found that a single OprF channel mainly exists in weakly conductive
      subconformations and switches to the fully open state for a short time only.
      Therefore, the low permeability of OprF reported earlier may be due to two
      factors: mainly to the paucity of the single domain conformer in the OprF
      population and secondly to the predominance of weakly conductive subconformations
      within the single domain conformer.

PMID- 16617059
TI  - Identification of the expressed form of human cytosolic phospholipase A2beta
      (cPLA2beta): cPLA2beta3 is a novel variant localized to mitochondria and early
      endosomes.
AB  - In this study, we identify the principal splice variant of human cytosolic
      phospholipase A(2)beta (cPLA(2)beta) (also known as Group IVB cPLA(2)) present in
      cells. In human lung, spleen, and ovary and in a lung epithelial cell line (BEAS
      2B), cPLA(2)beta is expressed as a 100-kDa protein, not the 114-kDa form
      originally predicted. Using RNA interference, the 100-kDa protein in BEAS-2B
      cells was confirmed to be cPLA(2)beta. BEAS-2B cells contain three different RNA
      splice variants of cPLA(2)beta (beta1, beta2, and beta3). cPLA(2)beta1 is
      identical to the previously cloned cPLA(2)beta, predicted to encode a 114-kDa
      protein. However, cPLA(2)beta2 and cPLA(2)beta3 splice variants are smaller and
      contain internal deletions in the catalytic domain. The 100-kDa cPLA(2)beta in
      BEAS-2B cells is the translated product of cPLA(2)beta3. cPLA(2)beta3 exhibits
      calcium-dependent PLA(2) activity against palmitoyl-arachidonyl
      phosphatidylethanolamine and low level lysophospholipase activity but no activity
      against phosphatidylcholine. Unlike Group IVA cPLA(2)alpha, cPLA(2)beta3 is
      constitutively bound to membrane in unstimulated cells, localizing to
      mitochondria and early endosomes. cPLA(2)beta3 is widely expressed in tissues,
      suggesting that it has a generalized function at these unique sites.

PMID- 16617062
TI  - High prevalence of type b beta-lactamase-non-producing ampicillin-resistant
      Haemophilus influenzae in meningitis: the situation in Japan where Hib vaccine
      has not been introduced.
AB  - OBJECTIVES: To study yearly changes in resistance and to identify ftsI mutations
      in beta-lactamase-non-producing ampicillin-resistant (BLNAR) and TEM-1 beta
      lactamase-producing amoxicillin/clavulanic acid-resistant (BLPACR) isolates of
      Haemophilus influenzae from patients with meningitis. METHODS: Between January
      2000 and December 2004, we received 621 isolates of H. influenzae from 285 member
      institutions of the Nationwide Surveillance Study Group for Bacterial Meningitis.
      All isolates were analysed by PCR to identify resistance genes and tested for
      susceptibility to beta-lactams. The ftsI gene was sequenced in all BLNAR and
      BLPACR isolates. RESULTS: All but four isolates were of serotype b. The isolates
      could be divided into six classes, namely beta-lactamase-non-producing ampicillin
      susceptible (25.0%), TEM-1 beta-lactamase-producing ampicillin-resistant (11.0%),
      beta-lactamase-non-producing low-level ampicillin-resistant with N526K or R517H
      substitution in the ftsI gene (30.4%), BLNAR with an S385T substitution together
      with either N526K or R517H substitution in ftsI (22.2%), BLPACR-I with either a
      N526K or R517H substitution in ftsI (9.5%) and BLPACR-II with an S385T
      substitution together with either a N526K or R517H substitution in ftsI (1.9%).
      The prevalence of BLNAR has increased rapidly, from 5.8% in 2000 to 34.5% in
      2004. All BLNAR and BLPACR-II strains were classified into nine subgroups on the
      basis of substitution patterns in the ftsI gene. The MICs of cephalosporin
      antibiotics for H. influenzae transformants into which the ftsI genes from BLNAR
      strains of each of the nine subgroups were introduced increased to varying
      degrees depending on the mutations. CONCLUSIONS: The results suggest that
      introduction of H. influenzae type b (Hib) vaccination into infants and children
      is necessary for the prevention of severe Hib infections in Japan.

PMID- 16617063
TI  - Azithromycin iv pharmacodynamic parameters predicting Streptococcus pneumoniae
      killing in epithelial lining fluid versus serum: an in vitro pharmacodynamic
      simulation.
AB  - OBJECTIVES: To investigate the azithromycin pharmacodynamic parameters predicting
      bacterial killing in epithelial lining fluid (ELF) versus serum against macrolide
      susceptible and -resistant Streptococcus pneumoniae isolates (with different
      resistance genotypes), through the simulation of concentrations achieved after a
      500 mg intravenous (iv) once a day regimen. METHODS: An in vitro computer
      controlled pharmacodynamic simulation of human azithromycin concentrations in
      serum and ELF was carried out, and colony counts were determined over 24 h. Four
      strains with MIC values (mg/L) of 0.5 [mef(A) and erm(B) negative], 2 [mef(A)
      positive and erm(B) negative], 8 [mef(A) positive and erm(B) negative] and 256
      [mef(A) negative and erm(B) positive] were used. RESULTS: Significant (P < 0.05)
      azithromycin antibacterial activity versus antibiotic-free controls was found in
      serum and ELF against the susceptible and mef(A) positive strains, but not
      against the erm(B) positive strain. AUC(0-24)/MIC values around or higher than 25
      were needed to achieve (time to 99.9% reduction of initial inocula of around 6 h)
      and maintain (24 h inocula reduction > or =3 log(10)cfu/mL) bactericidal activity
      without regrowth. This was achieved only with the susceptible strain in serum,
      but also with the mef(A) positive strain exhibiting an MIC of 2 mg/L in ELF.
      CONCLUSIONS: The results of this study support that the suggested breakpoint for
      susceptibility (< or =2 mg/L) may be adequate to predict S. pneumoniae
      eradication with ELF but not with serum concentrations obtained after a 500 mg iv
      once a day regimen.

PMID- 16617064
TI  - In vitro anticandidal activity of xanthorrhizol isolated from Curcuma
      xanthorrhiza Roxb.
AB  - OBJECTIVES: Xanthorrhizol, isolated from the methanol extract of Curcuma
      xanthorrhiza Roxb., was investigated for its anticandidal activity using six
      Candida species. METHODS: The in vitro susceptibility tests for xanthorrhizol
      were carried out in terms of MIC and minimal fungicidal concentration (MFC) using
      the NCCLS M27-A2 broth microdilution method. Time-kill curves were determined to
      assess the correlation between MIC and fungicidal activity of xanthorrhizol at
      concentrations ranging from 0 MIC to 4x MIC. RESULTS: All Candida species showed
      susceptibility to xanthorrhizol in the MIC range 1.0-15.0 mg/L for Candida
      albicans, 1.0-10 mg/L for Candida glabrata, 2.0-8.0 mg/L for Candida
      guilliermondii, 2.5-7.5 mg/L for Candida krusei, 2.5-25 mg/L for Candida
      parapsilosis and 2.0-8.0 mg/L for Candida tropicalis. Time-kill curves
      demonstrated that xanthorrhizol was able to kill the Candida strains with MFCs of
      20 mg/mL, 15 mg/mL, 12.5 mg/mL, 10 mg/L, 30 mg/mL and 10 mg/L for C. albicans, C.
      glabrata, C. guilliermondii, C. krusei, C. parapsilosis and C. tropicalis,
      respectively. CONCLUSIONS: The potent anticandidal activity of xanthorrhizol may
      support the use of C. xanthorriza for the treatment of candidiasis.

PMID- 16617065
TI  - A Pseudomonas aeruginosa isolate producing the GES-5 extended-spectrum beta
      lactamase.

PMID- 16617066
TI  - The past, present and future of antifolates in the treatment of Plasmodium
      falciparum infection.
AB  - Chemotherapy remains the most important means of controlling malaria, one of the
      deadliest infectious parasitic diseases in the world. Antimalarial antifolates
      have been central for prophylaxis and treatment of malaria. This drug family was
      discovered in the 1940s, during the Second World War, and molecules that are
      currently in clinical use were discovered at that time. Since the 1940s, no new
      antimalarial antifolates have been developed that have reached Phase I/II stages.
      Limited work has been carried out to exploit the inhibition of the malaria folate
      pathway as a means of discovering new drugs. In this review, work carried out on
      antimalarial antifolates since the 1940s up to the present time is discussed in
      terms of discovery, clinical use, mode of action and mechanism of resistance. New
      concepts have been presented to improve antimalarial antifolate in vivo efficacy
      and to identify potent new antifolate agents.

PMID- 16617067
TI  - Effective temperature in stochastic kinetics and gene networks.
AB  - The fluctuation-dissipation theorem, one of the central theorems in thermal
      dynamics, breaks down in out-of-equilibrium systems. The idea of effective
      temperature coming from the extensions of that theorem has been recently
      introduced to study glasses and has proved to be a key concept for out-of
      equilibrium systems. Gene networks involve stochastic chemical kinetics and are
      far from equilibrium. This leads us to try to use the notion of effective
      temperature to study them. To develop this idea, we study a simple birth-death
      process and a general two-species interacting process using the language of
      effective temperature. Furthermore, a model of a nonregulatory gene is studied as
      an example. The effective temperature may serves as an alternative and somewhat
      more fundamental language to describe the intrinsic-extrinsic noise distinction
      that has already provided a tool for qualifying gene networks.

PMID- 16617068
TI  - Kinetic definition of protein folding transition state ensembles and reaction
      coordinates.
AB  - Using distributed molecular dynamics simulations we located four distinct folding
      transitions for a 39-residue betabetaalphabeta protein fold. To characterize the
      nature of each room temperature transition, we calculated the probability of
      transmission for 500 points along each free energy barrier. We introduced a
      method for determining transition states by employing the transmission
      probability, Ptrans, and determined which conformations were transition state
      ensemble members (Ptrans approximately 0.5). The transmission probability may be
      used to characterize the barrier in several ways. For example, we ran simulations
      at 82 degrees C, determined the change in Ptrans with temperature for all 2,000
      conformations, and quantified Hammond behavior directly using Ptrans correlation.
      Additionally, we propose that diffusion along Ptrans may provide the
      configurational diffusion rate at the top of the barrier. Specifically, given a
      transition state conformation x0 with estimated Ptrans=0.5, we selected a large
      set of subsequent conformations from independent trajectories, each exactly a
      small time deltat after x0 (250 ps). Calculating Ptrans for the new trial
      conformations, we generated the P(Ptrans|deltat=250 ps) distribution that
      reflected diffusion. This approach provides a novel perspective on the diffusive
      nature of a protein folding transition and provides a framework for a
      quantitative study of activated relaxation kinetics.

PMID- 16617069
TI  - Effects of denaturants on the dynamics of loop formation in polypeptides.
AB  - Quenching of the triplet state of tryptophan by close contact with cysteine has
      been used to measure the reaction-limited and diffusion-limited rates of loop
      formation in disordered polypeptides having the sequence cys-(ala-gly-gln)j-trp
      (j=1-9). The decrease in the length-dependence of the reaction-limited rate for
      short chains in aqueous buffer, previously attributed to chain stiffness, is not
      observed at high concentrations of chemical denaturant (6 M GdmCl and 8 M urea),
      showing that denaturants increase chain flexibility. For long chains, both
      reaction-limited and diffusion-limited rates are significantly smaller in
      denaturant and exhibit a steeper length dependence. The results can be explained
      using end-to-end distributions from a wormlike chain model in which excluded
      volume interactions are incorporated by associating a 0.4-0.5 nm diameter hard
      sphere with the end of each virtual peptide bond. Fitting the data with this
      model shows that the denaturants reduce the persistence length from approximately
      0.6 nm to approximately 0.4 nm, only slightly greater than the length of a
      peptide bond. The same model also describes the reported length dependence for
      the radii of gyration of chemically denatured proteins containing 50-400
      residues. The end-to-end diffusion coefficients obtained from the diffusion
      limited rates are smaller than the sum of the monomer diffusion coefficients and
      exhibit significant temperature dependence, suggesting that diffusion is slowed
      by internal friction arising from barriers to backbone conformational changes.

PMID- 16617070
TI  - A computational framework for the topological analysis and targeted disruption of
      signal transduction networks.
AB  - In this article, optimization-based frameworks are introduced for elucidating the
      input-output structure of signaling networks and for pinpointing targeted
      disruptions leading to the silencing of undesirable outputs in therapeutic
      interventions. The frameworks are demonstrated on a large-scale reconstruction of
      a signaling network composed of nine signaling pathways implicated in prostate
      cancer. The Min-Input framework is used to exhaustively identify all input-output
      connections implied by the signaling network structure. Results reveal that there
      exist two distinct types of outputs in the signaling network that either can be
      elicited by many different input combinations or are highly specific requiring
      dedicated inputs. The Min-Interference framework is next used to precisely
      pinpoint key disruptions that negate undesirable outputs while leaving unaffected
      necessary ones. In addition to identifying disruptions of terminal steps, we also
      identify complex disruption combinations in upstream pathways that indirectly
      negate the targeted output by propagating their action through the signaling
      cascades. By comparing the obtained disruption targets with lists of drug
      molecules we find that many of these targets can be acted upon by existing drug
      compounds, whereas the remaining ones point at so-far unexplored targets. Overall
      the proposed computational frameworks can help elucidate input/output
      relationships of signaling networks and help to guide the systematic design of
      interference strategies.

PMID- 16617071
TI  - "Entropic traps" in the kinetics of phase separation in multicomponent membranes
      stabilize nanodomains.
AB  - We quantitatively describe the creation and evolution of phase-separated domains
      in a multicomponent lipid bilayer membrane. The early stages, termed the
      nucleation stage and the independent growth stage, are extremely rapid
      (characteristic times are submillisecond and millisecond, respectively) and the
      system consists of nanodomains of average radius approximately 5-50 nm. Next,
      mobility of domains becomes consequential; domain merger and fission become the
      dominant mechanisms of matter exchange, and line tension gamma is the main
      determinant of the domain size distribution at any point in time. For
      sufficiently small gamma, the decrease in the entropy term that results from
      domain merger is larger than the decrease in boundary energy, and only
      nanodomains are present. For large gamma, the decrease in boundary energy
      dominates the unfavorable entropy of merger, and merger leads to rapid
      enlargement of nanodomains to radii of micrometer scale. At intermediate line
      tensions and within finite times, nanodomains can remain dispersed and coexist
      with a new global phase. The theoretical critical value of line tension needed to
      rapidly form large rafts is in accord with the experimental estimate from the
      curvatures of budding domains in giant unilamellar vesicles.

PMID- 16617073
TI  - Quantifying the kinetic paths of flexible biomolecular recognition.
AB  - Biomolecular recognition often involves large conformational changes, sometimes
      even local unfolding. The identification of kinetic pathways has become a central
      issue in understanding the nature of binding. A new approach is proposed here to
      study the dynamics of this binding-folding process through the establishment of a
      path-integral framework on the underlying energy landscape. The dominant kinetic
      paths of binding and folding can be determined and quantified. The significant
      coupling between the binding and folding of biomolecules often exists in many
      important cellular processes. In this case, the corresponding kinetic paths of
      binding are shown to be intimately correlated with those of folding and the
      dynamics becomes quite cooperative. This implies that binding and folding happen
      concurrently. When the coupling between binding and folding is weak (strong), the
      kinetic process usually starts with significant folding (binding) first, with the
      binding (folding) later proceeding to the end. The kinetic rate can be obtained
      through the contributions from the dominant paths. The rate is shown to have a
      bell-shaped dependence on temperature in the concentration-saturated regime
      consistent with experiment. The changes of the kinetics that occur upon changing
      the parameters of the underlying binding-folding energy landscape are studied.

PMID- 16617072
TI  - Reaction diffusion modeling of calcium dynamics with realistic ER geometry.
AB  - We describe a finite-element model of mast cell calcium dynamics that
      incorporates the endoplasmic reticulum's complex geometry. The model is built
      upon a three-dimensional reconstruction of the endoplasmic reticulum (ER) from an
      electron tomographic tilt series. Tetrahedral meshes provide volumetric
      representations of the ER lumen, ER membrane, cytoplasm, and plasma membrane. The
      reaction-diffusion model simultaneously tracks changes in cytoplasmic and ER
      intraluminal calcium concentrations and includes luminal and cytoplasmic protein
      buffers. Transport fluxes via PMCA, SERCA, ER leakage, and Type II IP3 receptors
      are also represented. Unique features of the model include stochastic behavior of
      IP3 receptor calcium channels and comparisons of channel open times when
      diffusely distributed or aggregated in clusters on the ER surface. Simulations
      show that IP3R channels in close proximity modulate activity of their neighbors
      through local Ca2+ feedback effects. Cytoplasmic calcium levels rise higher, and
      ER luminal calcium concentrations drop lower, after IP3-mediated release from
      receptors in the diffuse configuration. Simulation results also suggest that the
      buffering capacity of the ER, and not restricted diffusion, is the predominant
      factor influencing average luminal calcium concentrations.

PMID- 16617074
TI  - Measuring optical and mechanical properties of a living cell with defocusing
      microscopy.
AB  - Defocusing microscopy (DM) is a recently developed technique that allows
      quantitative analysis of membrane surface dynamics of living cells using a simple
      bright-field optical microscope. According to DM, the contrast of defocused
      images is proportional to cell surface curvature. Although, until now, this
      technique was used mainly to determine size and amount of membrane shape
      fluctuations, such as ruffles and small random membrane fluctuations, in
      macrophages, its applications on cell biology extend beyond that. We show how DM
      can be used to measure optical and mechanical properties of a living macrophage,
      such as cell refractive index n, membrane bending modulus K(c), and effective
      cell viscosity eta for membrane-actin meshwork relaxation. Experimental data
      collected from defocused images of bone marrow-derived macrophages were used to
      evaluate these parameters. The obtained values, averaged over several different
      macrophages, are n = (1.384 +/- 0.015), K(c) approximately 3.2 x 10(-19) J, and
      eta approximately 459 Pa.s. We also estimate the amplitude of the small
      fluctuations to be of the order of 3 nm, which is around the step size of a
      polymerizing actin filament.

PMID- 16617075
TI  - Dynamics of muscle glycogenolysis modeled with pH time course computation and pH
      dependent reaction equilibria and enzyme kinetics.
AB  - Cellular metabolites are moieties defined by their specific binding constants to
      H+, Mg2+, and K+ or anions without ligands. As a consequence, every biochemical
      reaction in the cytoplasm has an associated proton stoichiometry that is
      generally noninteger- and pH-dependent. Therefore, with metabolic flux, pH is
      altered in a medium with finite buffer capacity. Apparent equilibrium constants
      and maximum enzyme velocities, which are functions of pH, are also altered. We
      augmented an earlier mathematical model of skeletal muscle glycogenolysis with pH
      dependent enzyme kinetics and reaction equilibria to compute the time course of
      pH changes. Analysis shows that kinetics and final equilibrium states of the
      closed system are highly constrained by the pH-dependent parameters. This kinetic
      model of glycogenolysis, coupled to creatine kinase and adenylate kinase,
      simulated published experiments made with a cell-free enzyme mixture to
      reconstitute the network and to synthesize PCr and lactate in vitro. Using the
      enzyme kinetic and thermodynamic data in the literature, the simulations required
      minimal adjustments of parameters to describe the data. These results show that
      incorporation of appropriate physical chemistry of the reactions with accurate
      kinetic modeling gives a reasonable simulation of experimental data and is
      necessary for a physically correct representation of the metabolic network. The
      approach is general for modeling metabolic networks beyond the specific pathway
      and conditions presented here.

PMID- 16617076
TI  - Pulsed laser microbeam-induced cell lysis: time-resolved imaging and analysis of
      hydrodynamic effects.
AB  - Time-resolved imaging was used to examine the use of pulsed laser microbeam
      irradiation to produce cell lysis. Lysis was accomplished through the delivery of
      6 ns, lambda=532 nm laser pulses via a 40x, 0.8 NA objective to a location 10
      microm above confluent monolayers of PtK2 cells. The process dynamics were
      examined at cell surface densities of 600 and 1000 cells/mm2 and pulse energies
      corresponding to 0.7x, 1x, 2x, and 3x the threshold for plasma formation. The
      cell lysis process was imaged at times of 0.5 ns to 50 micros after laser pulse
      delivery and revealed the processes of plasma formation, pressure wave
      propagation, and cavitation bubble dynamics. Cavitation bubble expansion was the
      primary agent of cell lysis with the zone of lysed cells fully established within
      600 ns of laser pulse delivery. The spatial extent of cell lysis increased with
      pulse energy but decreased with cell surface density. Hydrodynamic analysis
      indicated that cells subject to transient shear stresses in excess of a critical
      value were lysed while cells exposed to lower shear stresses remained adherent
      and viable. This critical shear stress is independent of laser pulse energy and
      varied from approximately 60-85 kPa for cell monolayers cultured at a density of
      600 cells/mm2 to approximately 180-220 kPa for a surface density of 1000
      cells/mm2. The implications for single cell lysis and microsurgery are discussed.

PMID- 16617078
TI  - Membrane elastic fluctuations and the insertion and tilt of beta-barrel proteins.
AB  - Folding of porin-like beta-barrel outer membrane proteins can be achieved in the
      presence of phospholipid vesicles, and takes place concurrently with
      incorporation into the membrane. The pronounced dependence found for the
      insertion of the protein OmpA on membrane thickness (Kleinschmidt, J. H., and L.
      K. Tamm. 2002. J. Mol. Biol. 324:319-330) is analyzed in terms of the effects of
      out-of-plane elastic fluctuations on the area dilation modulus (Evans, E., and W.
      Rawicz. 1990. Phys. Rev. Lett. 64:2094-2097). For unstrained large unilamellar
      vesicles, the elastic free energy for membrane insertion is predicted to depend
      on the fourth power of the membrane thickness. The influence of thermally induced
      bending fluctuations on the effective tilt of the OmpA beta-barrel in disaturated
      phosphatidylcholine membranes of different thicknesses (Ramakrishnan, M., J. Qu,
      C. L. Pocanschi, J. H. Kleinschmidt, and D. Marsh. 2005. Biochemistry. 44:3515
      3523) is also considered. A contribution to the orientational order parameter
      that scales as the inverse second power of the membrane thickness is predicted.

PMID- 16617077
TI  - Cations and hydration in catalytic RNA: molecular dynamics of the hepatitis delta
      virus ribozyme.
AB  - The hepatitis delta virus (HDV) ribozyme is an RNA enzyme from the human
      pathogenic HDV. Cations play a crucial role in self-cleavage of the HDV ribozyme,
      by promoting both folding and chemistry. Experimental studies have revealed
      limited but intriguing details on the location and structural and catalytic
      functions of metal ions. Here, we analyze a total of approximately 200 ns of
      explicit-solvent molecular dynamics simulations to provide a complementary
      atomistic view of the binding of monovalent and divalent cations as well as water
      molecules to reaction precursor and product forms of the HDV ribozyme. Our
      simulations find that an Mg2+ cation binds stably, by both inner- and outer
      sphere contacts, to the electronegative catalytic pocket of the reaction
      precursor, in a position to potentially support chemistry. In contrast,
      protonation of the catalytically involved C75 in the precursor or artificial
      placement of this Mg2+ into the product structure result in its swift expulsion
      from the active site. These findings are consistent with a concerted reaction
      mechanism in which C75 and hydrated Mg2+ act as general base and acid,
      respectively. Monovalent cations bind to the active site and elsewhere assisted
      by structurally bridging long-residency water molecules, but are generally
      delocalized.

PMID- 16617079
TI  - A buffering SERCA pump in models of calcium dynamics.
AB  - Many cells use oscillations in calcium concentration to transmit messages. The
      oscillations largely result from an influx of calcium into the cytosol from the
      endoplasmic reticulum (ER), followed by an efflux of calcium from the cytosol
      back into the ER. The sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA)
      pump pumps calcium into the ER. It binds calcium on the cytosolic side and
      releases it on the ER side and in the delay between binding and release, calcium
      is buffered by the pump. We developed a model of a buffering SERCA pump and
      investigated whether including this in a model of calcium oscillations has any
      significant effects. We found that the oscillations produced when using the SERCA
      pump, which does not buffer calcium, have a larger amplitude and a slightly
      smaller period than when using the buffering SERCA pump. We show that the
      buffering SERCA pump shows adaptation to a stimulus, and we demonstrate that, by
      using a bidirectional SERCA pump, we are able to eliminate futile cycling of
      calcium between the cytosol and ER when the cell is at rest.

PMID- 16617080
TI  - Fluorescence lifetime imaging provides enhanced contrast when imaging the phase
      sensitive dye di-4-ANEPPDHQ in model membranes and live cells.
AB  - We apply fluorescence lifetime imaging to the membrane phase-sensing dye di-4
      ANEPPDHQ in model membranes and live cells. We show that the 1700 ps lifetime
      shift between liquid-disordered and liquid-ordered phases offers greater contrast
      than the 60 nm spectral shift previously reported. Detection of cholesterol-rich
      membrane microdomains is confirmed by observation of the temperature dependence
      of membrane order and by cholesterol depletion using methyl-beta-cyclodextrin.

PMID- 16617081
TI  - Proton transfer in gramicidin water wires in phospholipid bilayers: attenuation
      by phosphoethanolamine.
AB  - The transfer of protons in water wires was studied in native gramicidin A (gA),
      and in the SS- and RR-diastereoisomers of dioxolane-linked gA channels (SS and RR
      channels). These peptides were incorporated into membranes comprised of distinct
      combinations of phospholipid headgroups and acyl chains. Quantitative
      relationships between single channel conductances to H+ (g(H)) and [H+] were
      determined in distinct phospholipid membranes, and are in remarkable contrast
      with results previously obtained in monoglyceride membranes. In particular: 1),
      g(H)-[H+] relationships for the various gA channels in distinct phospholipid
      membranes are well fitted by single adsorption isotherms. A simple kinetic model
      assuming mono-occupancy of channels by protons fits said relationships. This does
      not occur with monoglyceride membranes. 2), Under nonsaturating [H+], g(H) is
      approximately 1 order of magnitude larger in phospholipid than in monoglyceride
      membranes. 3), Differences between rates of H+ transfer in various gA channels
      are still present but considerably attenuated in phospholipid relative to
      monoglyceride membranes. 4), Charged phospholipid headgroups affect g(H) via
      changes in [H+] at the membrane/solution interfaces. 5), Phosphoethanolamine
      groups caused a marked attenuation of g(H) relative to membranes with other
      phospholipid headgroups. This attenuation is voltage-dependent and tends to
      saturate H+ currents at voltages larger than 250 mV. This effect is likely to
      occur by limiting the access and exit of H+ in and out of the channel due to
      relatively strong oriented H-bonds between waters and phosphoethanolamine groups
      at channel interfaces. The differential effects of phospholipids on proton
      transfer could be reasoned by considering solvation effects of side chain
      residues of gramicidin channels by double acyl chains and by the presence of
      polar headgroups facilitating the entrance/exit of protons through the channel
      mouths.

PMID- 16617082
TI  - Translocation of phospholipids and dithionite permeability in liquid-ordered and
      liquid-disordered membranes.
AB  - We present a detailed study of the translocation rate of two headgroup-labeled
      phospholipid derivatives, one with two acyl chains, NBD-DMPE, and the other with
      a single acyl chain, NBD-lysoMPE, in lipid bilayer membranes in the liquid
      disordered state (POPC) and in the liquid-ordered states (POPC/cholesterol
      (Chol), molar ratio 1:1, and sphingomyelin (SpM)/Chol, molar ratio 6:4). The
      study was performed as a function of temperature and the thermodynamic parameters
      of the translocation process have been obtained. The most important findings are
      1), the translocation of NBD-DMPE is significantly faster than the translocation
      of NBD-lysoMPE for all bilayer compositions and temperatures tested; and 2), for
      both phospholipid derivatives, the translocation in POPC bilayers is
      approximately 1 order of magnitude faster than in POPC/Chol (1:1) bilayers and
      approximately 2-3 orders of magnitude faster than in SpM/Chol (6:4) bilayers. The
      permeability of the lipid bilayers to dithionite has also been measured. In
      liquid disordered membranes, the permeability rate constant obtained is
      comparable to the translocation rate constant of NBD-DMPE. However, in liquid
      ordered bilayers, the permeability of dithionite is significantly faster then the
      translocation of NBD-DMPE. The change in enthalpy and entropy associated with the
      formation of the activated state in the translocation and permeation processes
      has also been obtained.

PMID- 16617083
TI  - Controlling the protein dynamical transition with sugar-based bioprotectant
      matrices: a neutron scattering study.
AB  - Through elastic neutron scattering we measured the mean-square displacements of
      the hydrogen atoms of lysozyme embedded in a glucose-water glassy matrix as a
      function of the temperature and at various water contents. The elastic intensity
      of all the samples has been interpreted in terms of the double-well model in the
      whole temperature range. The dry sample shows an onset of anharmonicity at
      approximately 100 K, which can be attributed to the activation of methyl group
      reorientations. Such a protein intrinsic dynamics is decoupled from the external
      environment on the whole investigated temperature range. In the hydrated samples
      an additional and larger anharmonic contribution is provided by the protein
      dynamical transition, which appears at a higher temperature Td. As hydration
      increases the coupling between the protein internal dynamics and the surrounding
      matrix relaxations becomes more effective. The behavior of Td that, as a function
      of the water content, diminishes by approximately 60 K, supports the picture of
      the protein dynamics as driven by solvent relaxations. A possible connection
      between the protein dynamical response versus T and the thermal stability in
      glucose-water bioprotectant matrices is proposed.

PMID- 16617084
TI  - Mechanical properties of pore-spanning lipid bilayers probed by atomic force
      microscopy.
AB  - We measure the elastic response of a free-standing lipid membrane to a local
      indentation by using an atomic force microscope. Starting point is a planar gold
      coated alumina substrate with a chemisorbed 3-mercaptopropionic acid monolayer
      displaying circular pores of very well defined and tunable size, over which
      bilayers composed of N,N,-dimethyl-N,N,-dioctadecylammonium bromide or 1,2
      dioleoyl-3-trimethylammonium-propane chloride were spread. Centrally indenting
      these "nanodrums" with an atomic force microscope tip yields force-indentation
      curves, which we quantitatively analyze by solving the corresponding shape
      equations of continuum curvature elasticity. Since the measured response depends
      in a known way on the system geometry (pore size, tip radius) and on material
      parameters (bending modulus, lateral tension), this opens the possibility to
      monitor local elastic properties of lipid membranes in a well-controlled setting.

PMID- 16617085
TI  - Closer look at structure of fully hydrated fluid phase DPPC bilayers.
AB  - X-ray data are presented for the benchmark dipalmitoylphosphatidylcholine lipid
      bilayer in the most biologically relevant state in which the bilayers are fully
      hydrated and in the fluid (liquid-crystalline) phase. Form factors F(q(z)) are
      obtained from a combination of two sample preparations, oriented stacks of
      bilayers for q(z) extending to 0.85 A(-1) and unilamellar vesicles for smaller
      q(z). Modeling obtains the electron density profile and values for the area per
      molecule, for the locations of the component groups, and for the different types
      of thicknesses of the bilayer, such as the hydrocarbon thickness and the steric
      thickness.

PMID- 16617086
TI  - Ensemble-based convergence analysis of biomolecular trajectories.
AB  - Assessing the convergence of a biomolecular simulation is an essential part of
      any careful computational investigation, because many fundamental aspects of
      molecular behavior depend on the relative populations of different conformers.
      Here we present a physically intuitive method to self-consistently assess the
      convergence of trajectories generated by molecular dynamics and related methods.
      Our approach reports directly and systematically on the structural diversity of a
      simulation trajectory. Straightforward clustering and classification steps are
      the key ingredients, allowing the approach to be trivially applied to systems of
      any size. Our initial study on met-enkephalin strongly suggests that even fairly
      long trajectories (approximately 50 ns) may not be converged for this small--but
      highly flexible--system.

PMID- 16617087
TI  - Increasing the net charge and decreasing the hydrophobicity of bovine carbonic
      anhydrase decreases the rate of denaturation with sodium dodecyl sulfate.
AB  - This study compares the rate of denaturation with sodium dodecyl sulfate (SDS) of
      the individual rungs of protein charge ladders generated by acylation of the
      lysine epsilon-NH3+ groups of bovine carbonic anhydrase II (BCA). Each acylation
      decreases the number of positively charged groups, increases the net negative
      charge, and increases the hydrophobic surface area of BCA. This study reports the
      kinetics of denaturation in solutions containing SDS of the protein charge
      ladders generated with acetic and hexanoic anhydrides; plotting these rates of
      denaturation as a function of the number of modifications yields a U-shaped
      curve. The proteins with an intermediate number of modifications are the most
      stable to denaturation by SDS. There are four competing interactions-two
      resulting from the change in electrostatics and two resulting from the change in
      exposed hydrophobic surface area-that determine how a modification affects the
      stability of a rung of a charge ladder of BCA to denaturation with SDS. A model
      based on assumptions about how these interactions affect the folded and
      transition states has been developed and fits the experimental results. Modeling
      indicates that for each additional acylation, the magnitude of the change in the
      activation energy of denaturation (DeltaDeltaG(double dagger)) due to changes in
      the electrostatics is much larger than the change in DeltaDeltaG(double dagger)
      due to changes in the hydrophobicity, but the intermolecular and intramolecular
      electrostatic effects are opposite in sign. At the high numbers of acylations,
      hydrophobic interactions cause the hexanoyl-modified BCA to denature nearly three
      orders of magnitude more rapidly than the acetyl-modified BCA.

PMID- 16617088
TI  - Triggering and visualizing the aggregation and fusion of lipid membranes in
      microfluidic chambers.
AB  - We present a method that makes it possible to trigger, observe, and quantify
      membrane aggregation and fusion of giant liposomes in microfluidic chambers.
      Using electroformation from spin-coated films of lipids on transparent indium tin
      oxide electrodes, we formed two-dimensional networks of closely packed, surface
      attached giant liposomes. We investigated the effects of fusogenic agents by
      simply flowing these molecules into the chambers and analyzing the resulting
      shape changes of more than 100 liposomes in parallel. We used this setup to
      quantify membrane fusion by several well-studied mechanisms, including fusion
      triggered by Ca2+, polyethylene glycol, and biospecific tethering. Directly
      observing many liposomes simultaneously proved particularly useful for studying
      fusion events in the presence of low concentrations of fusogenic agents, when
      fusion was rare and probabilistic. We applied this microfluidic fusion assay to
      investigate a novel 30-mer peptide derived from a recently identified human
      receptor protein, B5, that is important for membrane fusion during the entry of
      herpes simplex virus into host cells. This peptide triggered fusion of liposomes
      at an approximately 6 times higher probability than control peptides and caused
      irreversible interactions between adjacent membranes; it was, however, less
      fusogenic than Ca2+ at comparable concentrations. Closely packed, surface
      attached giant liposomes in microfluidic chambers offer a method to observe
      membrane aggregation and fusion in parallel without requiring the use of
      micromanipulators. This technique makes it possible to characterize rapidly novel
      fusogenic agents under well-defined conditions.

PMID- 16617089
TI  - Langevin dynamics simulations of genome packing in bacteriophage.
AB  - We use Langevin dynamics simulations to study the process by which a coarse
      grained DNA chain is packaged within an icosahedral container. We focus our
      inquiry on three areas of interest in viral packing: the evolving structure of
      the packaged DNA condensate; the packing velocity; and the internal buildup of
      energy and resultant forces. Each of these areas has been studied experimentally,
      and we find that we can qualitatively reproduce experimental results. However,
      our findings also suggest that the phage genome packing process is fundamentally
      different than that suggested by the inverse spool model. We suggest that packing
      in general does not proceed in the deterministic fashion of the inverse-spool
      model, but rather is stochastic in character. As the chain configuration becomes
      compressed within the capsid, the structure, energy, and packing velocity all
      become dependent upon polymer dynamics. That many observed features of the
      packing process are rooted in condensed-phase polymer dynamics suggests that
      statistical mechanics, rather than mechanics, should serve as the proper
      theoretical basis for genome packing. Finally we suggest that, as a result of an
      internal protein unique to bacteriophage T7, the T7 genome may be significantly
      more ordered than is true for bacteriophage in general.

PMID- 16617090
TI  - Subcellular localization and membrane topology of the melon ethylene receptor
      CmERS1.
AB  - Ethylene receptors are multispanning membrane proteins that negatively regulate
      ethylene responses via the formation of a signaling complex with downstream
      elements. To better understand their biochemical functions, we investigated the
      membrane topology and subcellular localization of CmERS1, a melon (Cucumis melo)
      ethylene receptor that has three putative transmembrane domains at the N
      terminus. Analyses using membrane fractionation and green fluorescent protein
      imaging approaches indicate that CmERS1 is predominantly associated with the
      endoplasmic reticulum (ER) membrane. Detergent treatments of melon microsomes
      showed that the receptor protein is integrally bound to the ER membrane. A
      protease protection assay and N-glycosylation analysis were used to determine
      membrane topology. The results indicate that CmERS1 spans the membrane three
      times, with its N terminus facing the luminal space and the large C-terminal
      portion lying on the cytosolic side of the ER membrane. This orientation provides
      a platform for interaction with the cytosolic signaling elements. The three N
      terminal transmembrane segments were found to function as topogenic sequences to
      determine the final topology. High conservation of these topogenic sequences in
      all ethylene receptor homologs identified thus far suggests that these proteins
      may share the same membrane topology.

PMID- 16617091
TI  - Systematic analysis of Arabidopsis organelles and a protein localization database
      for facilitating fluorescent tagging of full-length Arabidopsis proteins.
AB  - Cells are organized into a complex network of subcellular compartments that are
      specialized for various biological functions. Subcellular location is an
      important attribute of protein function. To facilitate systematic elucidation of
      protein subcellular location, we analyzed experimentally verified protein
      localization data of 1,300 Arabidopsis (Arabidopsis thaliana) proteins. The 1,300
      experimentally verified proteins are distributed among 40 different compartments,
      with most of the proteins localized to four compartments: mitochondria (36%),
      nucleus (28%), plastid (17%), and cytosol (13.3%). About 19% of the proteins are
      found in multiple compartments, in which a high proportion (36.4%) is localized
      to both cytosol and nucleus. Characterization of the overrepresented Gene
      Ontology molecular functions and biological processes suggests that the Golgi
      apparatus and peroxisome may play more diverse functions but are involved in more
      specialized processes than other compartments. To support systematic empirical
      determination of protein subcellular localization using a technology called
      fluorescent tagging of full-length proteins, we developed a database and Web
      application to provide preselected green fluorescent protein insertion position
      and primer sequences for all Arabidopsis proteins to study their subcellular
      localization and to store experimentally verified protein localization images,
      videos, and their annotations of proteins generated using the fluorescent tagging
      of full-length proteins technology. The database can be searched, browsed, and
      downloaded using a Web browser at http://aztec.stanford.edu/gfp/. The software
      can also be downloaded from the same Web site for local installation.

PMID- 16617092
TI  - Mutations in the microRNA complementarity site of the INCURVATA4 gene perturb
      meristem function and adaxialize lateral organs in arabidopsis.
AB  - Here, we describe how the semidominant, gain-of-function icu4-1 and icu4-2
      alleles of the INCURVATA4 (ICU4) gene alter leaf phyllotaxis and cell
      organization in the root apical meristem, reduce root length, and cause xylem
      overgrowth in the stem. The ICU4 gene was positionally cloned and found to encode
      the ATHB15 transcription factor, a class III homeodomain/leucine zipper family
      member, recently named CORONA. The icu4-1 and icu4-2 alleles bear the same point
      mutation that affects the microRNA complementarity site of ICU4 and is identical
      to those of several semidominant alleles of the class III homeodomain/leucine
      zipper family members PHABULOSA and PHAVOLUTA. The icu4-1 and icu4-2 mutations
      significantly increase leaf transcript levels of the ICU4 gene. The null hst-1
      allele of the HASTY gene, which encodes a nucleocytoplasmic transporter,
      synergistically interacts with icu4-1, the double mutant displaying partial
      adaxialization of rosette leaves and carpels. Our results suggest that the ICU4
      gene has an adaxializing function and that it is down-regulated by microRNAs that
      require the HASTY protein for their biogenesis.

PMID- 16617093
TI  - SERPINB1 upregulation is associated with in vivo complex formation with
      neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary
      dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) continues to be a major cause of morbidity in
      premature infants. An imbalance between neutrophil elastase and its inhibitors
      has been implicated in BPD. Serine protease inhibitor (SERPIN)B1 is an inhibitor
      of neutrophil proteases, including neutrophil elastase (NE) and cathepsin G (cat
      G). Recent studies suggest that SERPINB1 could provide protection in the airways
      by regulating excess protease activity associated with inflammatory lung
      disorders. In this study, we determined the distribution and ontogeny of SERPINB1
      in the baboon lung and characterized the expression of SERPINB1 in baboon models
      of BPD. SERPINB1 expression was detected in the conducting airway and glandular
      epithelial cells in addition to neutrophils, macrophages, and mast cells.
      SERPINB1 mRNA and protein expression increased with advancing gestational age and
      in the new BPD model. In contrast, SERPINB1 expression levels were decreased in
      the old BPD model. Furthermore, SERPINB1 was detected as a high-molecular-mass
      (HMM) complex in lung tissue and bronchoalveolar lavage fluid samples from the
      BPD group. Analysis of the HMM complex by coimmunoprecipitation showed that these
      complexes were formed between SERPINB1 and NE or cat G. High-performance liquid
      chromatography (HPLC) ion trap mass spectrometry verified the presence of
      SERPINB1 in HMM complexes. Finally, NE activity level was compared between new
      and old baboon models of BPD and was found to be significantly lower in new BPD.
      Thus SERPINB1 upregulation in new BPD may be protective by contributing to the
      regulation of neutrophil proteases NE and cat G.

PMID- 16617094
TI  - GRO-alpha regulation in airway smooth muscle by IL-1beta and TNF-alpha: role of
      NF-kappaB and MAP kinases.
AB  - Airway smooth muscle cells (ASMC) are a source of inflammatory chemokines that
      may propagate airway inflammatory responses. We investigated the production of
      the CXC chemokine growth-related oncogene protein-alpha (GRO-alpha) from ASMC
      induced by cytokines and the role of MAPK and NF-kappaB pathways. ASMC were
      cultured from human airways, grown to confluence, and exposed to cytokines IL
      1beta and TNF-alpha after growth arrest. GRO-alpha release, measured by ELISA,
      was increased by >50-fold after IL-1beta (0.1 ng/ml) or 5-fold after TNF-alpha (1
      ng/ml) in a dose- and time-dependent manner. GRO-alpha release was not affected
      by the T helper type 2 cytokines IL-4, IL-10, and IL-13. IL-1beta and TNF-alpha
      also induced GRO-alpha mRNA expression. Supernatants from IL-1beta-stimulated
      ASMC were chemotactic for neutrophils; this effect was inhibited by anti-GRO
      alpha blocking antibody. AS-602868, an inhibitor of IKK-2, and PD-98059, an
      inhibitor of ERK, inhibited GRO-alpha release and mRNA expression, whereas SP
      600125, an inhibitor of JNK, reduced GRO-alpha release without effect on mRNA
      expression. SB-203580, an inhibitor of p38 MAPK, had no effect. AS-602868 but not
      PD-98059 or SP-600125 inhibited p65 DNA-binding induced by IL-1beta and TNF
      alpha. By chromatin immunoprecipitation assay, IL-1beta and TNF-alpha enhanced
      p65 binding to the GRO-alpha promoter, which was inhibited by AS-602868. IL-1beta
      and TNF-alpha-stimulated expression of GRO-alpha from ASMC is regulated by
      independent pathways involving NF-kappaB activation and ERK and JNK pathways. GRO
      alpha released from ASMC participates in neutrophil chemotaxis.

PMID- 16617095
TI  - Apoptosis of pulmonary microvascular endothelial cells stimulates vascular smooth
      muscle cell growth.
AB  - We have previously hypothesized that the development of severe angioproliferative
      pulmonary hypertension is associated with not only initial endothelial cell (EC)
      apoptosis followed by the emergence of apoptosis-resistant proliferating EC but
      also with proliferation of vascular smooth muscle cells (VSMC). We have
      demonstrated that EC death results in the selection of an apoptosis-resistant,
      proliferating, and phenotypically altered EC phenotype. We postulate here that
      the initial apoptosis of EC induces the release of mediators that cause VSMC
      proliferation. We cultured EC in an artificial capillary CellMax system designed
      to simulate the highly efficient functions of the human capillary system. We
      induced apoptosis of microvascular EC using shear stress and the combined VEGF
      receptor (VEGFR-1 and -2) inhibitor SU-5416. Flow cytometry for the proliferation
      marker bromodeoxyuridine showed that serum-free medium conditioned by apoptosed
      EC induced proliferation of VSMC, whereas serum-free medium conditioned by
      nonapoptosed EC did not. We also show that medium conditioned by apoptosed EC is
      characterized by increased concentrations of transforming growth factor (TGF)
      beta1 and VEGF compared with medium conditioned by nonapoptosed EC and that TGF
      beta1 blockade prevented the proliferation of cultured VSMC. In conclusion, EC
      death induced by high shear stress and VEGFR blockade leads to the production of
      factors, in particular TGF-beta1, that activate VSMC proliferation.

PMID- 16617096
TI  - Role of caveolin-1 in p42/p44 MAP kinase activation and proliferation of human
      airway smooth muscle.
AB  - Chronic airways diseases, including asthma, are associated with an increased
      airway smooth muscle (ASM) mass, which may contribute to chronic airway
      hyperresponsiveness. Increased muscle mass is due, in part, to increased ASM
      proliferation, although the precise molecular mechanisms for this response are
      not completely clear. Caveolae, which are abundant in smooth muscle cells, are
      membrane microdomains where receptors and signaling effectors can be sequestered.
      We hypothesized that caveolae and caveolin-1 play an important regulatory role in
      ASM proliferation. Therefore, we investigated their role in p42/p44 MAPK
      signaling and proliferation using human ASM cell lines. Disruption of caveolae
      using methyl-beta-cyclodextrin and small interfering (si)RNA-knockdown of
      caveolin-1 caused spontaneous p42/p44 MAPK activation; additionally, caveolin-1
      siRNA induced ASM proliferation in mitogen deficient conditions, suggesting a key
      role for caveolae and caveolin-1 in maintaining quiescence. Moreover, caveolin-1
      accumulates twofold in myocytes induced to a contractile phenotype compared with
      proliferating ASM cells. Caveolin-1 siRNA failed to increase PDGF-induced p42/p44
      MAPK activation and cell proliferation, however, indicating that PDGF stimulation
      actively reversed the antimitogenic control by caveolin-1. Notably, the PDGF
      induced loss of antimitogenic control by caveolin-1 coincided with a marked
      increase in caveolin-1 phosphorylation. Furthermore, the strong association of
      PDGF receptor-beta with caveolin-1 that exists in quiescent cells was rapidly and
      markedly reduced with agonist addition. This suggests a dynamic relationship in
      which mitogen stimulation actively reverses caveolin-1 suppression of p42/p44
      MAPK signal transduction. As such, caveolae and caveolin-1 coordinate PDGF
      receptor signaling, leading to myocyte proliferation, and inhibit constitutive
      activity of p42/p44 MAPK to sustain cell quiescence.

PMID- 16617097
TI  - Detection of allergen-induced airway hyperresponsiveness in isolated mouse lungs.
AB  - Airway hyperresponsiveness (AHR) is a hallmark of bronchial asthma. Important
      features of this exaggerated response to bronchoconstrictive stimuli have mostly
      been investigated in vivo in intact animals or in vitro in isolated tracheal or
      bronchial tissues. Both approaches have important advantages but also certain
      limitations. Therefore, the aim of our study was to develop an ex vivo model of
      isolated lungs from sensitized mice for the investigation of airway
      responsiveness (AR). BALB/c mice were sensitized by intraperitoneal ovalbumin
      (Ova) and subsequently challenged by Ova inhalation. In vivo AR was measured in
      unrestrained animals by whole body plethysmography after stimulation with
      aerosolized methacholine (MCh) with determination of enhanced pause (P(enh)).
      Twenty-four hours after each P(enh) measurement, airway resistance was
      continuously registered in isolated, perfused, and ventilated lungs on
      stimulation with inhaled or intravascular MCh or nebulized Ova. In a subset of
      experiments, in vivo AR was additionally measured in orotracheally intubated,
      spontaneously breathing mice 24 h after P(enh) measurement, and lungs were
      isolated further 24 h later. Isolated lungs of allergen-sensitized and 
      challenged mice showed increased AR after MCh inhalation or infusion as well as
      after specific provocation with aerosolized allergen. AR was increased on days 2
      and 5 after Ova challenge and had returned to baseline on day 9. AHR in isolated
      lungs after aerosolized or intravascular MCh strongly correlated with in vivo AR.
      Pretreatment of isolated lungs with the beta(2)-agonist fenoterol diminished AR.
      In conclusion, this model provides new opportunities to investigate mechanisms of
      AHR as well as pharmacological interventions on an intact organ level.

PMID- 16617098
TI  - Independent ancient polyploidy events in the sister families Brassicaceae and
      Cleomaceae.
AB  - Recent studies have elucidated the ancient polyploid history of the Arabidopsis
      thaliana (Brassicaceae) genome. The studies concur that there was at least one
      polyploidy event occurring some 14.5 to 86 million years ago (Mya), possibly near
      the divergence of the Brassicaceae from its sister family, Cleomaceae. Using a
      comparative genomics approach, we asked whether this polyploidy event was unique
      to members of the Brassicaceae, shared with the Cleomaceae, or an independent
      polyploidy event in each lineage. We isolated and sequenced three genomic regions
      from diploid Cleome spinosa (Cleomaceae) that are each homoeologous to a
      duplicated region shared between At3 and At5, centered on the paralogs of
      SEPALLATA (SEP) and CONSTANS (CO). Phylogenetic reconstructions and analysis of
      synonymous substitution rates support the hypothesis that a genomic triplication
      in Cleome occurred independently of and more recently than the duplication event
      in the Brassicaceae. There is a strong correlation in the copy number (single
      versus duplicate) of individual genes, suggesting functionally consistent
      influences operating on gene copy number in these two independently evolving
      lineages. However, the amount of gene loss in Cleome is greater than in
      Arabidopsis. The genome of C. spinosa is only 1.9 times the size of A. thaliana,
      enabling comparative genome analysis of separate but related polyploidy events.

PMID- 16617099
TI  - The molecular basis of temperature compensation in the Arabidopsis circadian
      clock.
AB  - Circadian clocks maintain robust and accurate timing over a broad range of
      physiological temperatures, a characteristic termed temperature compensation. In
      Arabidopsis thaliana, ambient temperature affects the rhythmic accumulation of
      transcripts encoding the clock components TIMING OF CAB EXPRESSION1 (TOC1),
      GIGANTEA (GI), and the partially redundant genes CIRCADIAN CLOCK ASSOCIATED1
      (CCA1) and LATE ELONGATED HYPOCOTYL (LHY). The amplitude and peak levels increase
      for TOC1 and GI RNA rhythms as the temperature increases (from 17 to 27 degrees
      C), whereas they decrease for LHY. However, as temperatures decrease (from 17 to
      12 degrees C), CCA1 and LHY RNA rhythms increase in amplitude and peak expression
      level. At 27 degrees C, a dynamic balance between GI and LHY allows temperature
      compensation in wild-type plants, but circadian function is impaired in lhy and
      gi mutant plants. However, at 12 degrees C, CCA1 has more effect on the buffering
      mechanism than LHY, as the cca1 and gi mutations impair circadian rhythms more
      than lhy at the lower temperature. At 17 degrees C, GI is apparently dispensable
      for free-running circadian rhythms, although partial GI function can affect
      circadian period. Numerical simulations using the interlocking-loop model show
      that balancing LHY/CCA1 function against GI and other evening-expressed genes can
      largely account for temperature compensation in wild-type plants and the
      temperature-specific phenotypes of gi mutants.

PMID- 16617100
TI  - Multiple vacuolar sorting determinants exist in soybean 11S globulin.
AB  - The sorting determinants of glycinin, a soybean (Glycine max) 11S globulin, which
      mediates protein targeting to the protein storage vacuole (PSV), were
      investigated in maturing soybean cotyledons by transient expression assays. A C
      terminal stretch of 10 amino acids of A1aB1b, a glycinin group I subunit, was
      sufficient to direct green fluorescent protein (GFP) to the PSV. This peptide may
      correspond to a C-terminal vacuolar sorting determinant (ctVSD). Because
      functional inhibition of this putative ctVSD of A1aB1b did not block PSV sorting
      of A1aB1b, we used the three-dimensional structure of A1aB1b to identify
      candidates for a sequence-specific determinant (ssVSD). We found that the
      sequence downstream of disordered region 4 could direct GFP to the PSV and that
      Ile-297 is critical for sorting. However, functional inhibition of the ctVSD,
      combined with the Ile297Gly mutation, did not abolish the vacuolar sorting of
      A1aB1b, suggesting that A1aB1b has a third sorting determinant in addition to
      ctVSD and ssVSD. A glycinin group II subunit, A3B4, lacked a ctVSD but contained
      a VSD reminiscent of an ssVSD and an additional sorting determinant. We also
      demonstrate, by expression of dominant negative mutants of small GTPases and drug
      treatment experiments, that the trafficking of A1aB1b is COPII vesicle-dependent
      and wortmannin- and brefeldin A-sensitive.

PMID- 16617101
TI  - Functional analysis of an Arabidopsis transcription factor, DREB2A, involved in
      drought-responsive gene expression.
AB  - Transcription factors DREB1A/CBF3 and DREB2A specifically interact with cis
      acting dehydration-responsive element/C-repeat (DRE/CRT) involved in cold and
      drought stress-responsive gene expression in Arabidopsis thaliana. Intact DREB2A
      expression does not activate downstream genes under normal growth conditions,
      suggesting that DREB2A requires posttranslational modification for activation,
      but the activation mechanism has not been clarified. DREB2A domain analysis using
      Arabidopsis protoplasts identified a transcriptional activation domain between
      residues 254 and 335, and deletion of a region between residues 136 and 165
      transforms DREB2A to a constitutive active form. Overexpression of constitutive
      active DREB2A resulted in significant drought stress tolerance but only slight
      freezing tolerance in transgenic Arabidopsis plants. Microarray and RNA gel blot
      analyses revealed that DREB2A regulates expression of many water stress-inducible
      genes. However, some genes downstream of DREB2A are not downstream of DREB1A,
      which also recognizes DRE/CRT but functions in cold stress-responsive gene
      expression. Synthetic green fluorescent protein gave a strong signal in the
      nucleus under unstressed control conditions when fused to constitutive active
      DREB2A but only a weak signal when fused to full-length DREB2A. The region
      between DREB2A residues 136 and 165 plays a role in the stability of this protein
      in the nucleus, which is important for protein activation.

PMID- 16617102
TI  - MTA1, a transcriptional activator of breast cancer amplified sequence 3.
AB  - Here we define a function of metastasis-associated protein 1 (MTA1), a presumed
      corepressor of estrogen receptor alpha (ERalpha), as a transcriptional activator
      of Breast Cancer Amplified Sequence 3 (BCAS3), a gene amplified and overexpressed
      in breast cancers. We identified BCAS3 as a MTA1 chromatin target in a functional
      genomic screen. MTA1 stimulation of BCAS3 transcription required ERalpha and
      involved a functional ERE half-site in BCAS3. Furthermore, we discovered that
      MTA1 is acetylated on lysine 626, and that this acetylation is necessary for a
      productive transcriptional recruitment of RNA polymerase II complex to the BCAS3
      enhancer sequence. BCAS3 expression was elevated in mammary tumors from MTA1
      transgenic mice and 60% of the human breast tumors, and correlated with the
      coexpression of MTA1 as well as with tumor grade and proliferation of primary
      breast tumor samples. These findings reveal a previously unrecognized function of
      MTA1 in stimulating BCAS3 expression and suggest an important role for MTA1-BCAS3
      pathway in promoting cancerous phenotypes in breast tumor cells.

PMID- 16617103
TI  - A live, attenuated recombinant West Nile virus vaccine.
AB  - West Nile (WN) virus is an important cause of febrile exanthem and encephalitis.
      Since it invaded the U.S. in 1999, >19,000 human cases have been reported. The
      threat of continued epidemics has spurred efforts to develop vaccines. ChimeriVax
      WN02 is a live, attenuated recombinant vaccine constructed from an infectious
      clone of yellow fever (YF) 17D virus in which the premembrane and envelope genes
      of 17D have been replaced by the corresponding genes of WN virus. Preclinical
      tests in monkeys defined sites of vaccine virus replication in vivo. ChimeriVax
      WN02 and YF 17D had similar biodistribution but different multiplication
      kinetics. Prominent sites of replication were skin and lymphoid tissues,
      generally sparing vital organs. Viruses were cleared from blood by day 7 and from
      tissues around day 14. In a clinical study, healthy adults were inoculated with
      5.0 log(10) plaque-forming units (PFU) (n = 30) or 3.0 log10 PFU (n = 15) of
      ChimeriVax-WN02, commercial YF vaccine (YF-VAX, n = 5), or placebo (n = 30). The
      incidence of adverse events in subjects receiving the vaccine was similar to that
      in the placebo group. Transient viremia was detected in 42 of 45 (93%) of
      ChimeriVax-WN02 subjects, and four of five (80%) of YF-VAX subjects. All subjects
      developed neutralizing antibodies to WN or YF, respectively, and the majority
      developed specific T cell responses. ChimeriVax-WN02 rapidly elicits strong
      immune responses after a single dose, and is a promising candidate warranting
      further evaluation for prevention of WN disease.

PMID- 16617104
TI  - Dual roles for the trimeric G protein Go in asymmetric cell division in
      Drosophila.
AB  - During asymmetric division, a cell polarizes and differentially distributes
      components to its opposite ends. The subsequent division differentially
      segregates the two component pools to the daughters, which thereby inherit
      different developmental directives. In Drosophila sensory organ precursor cells,
      the localization of Numb protein to the cell's anterior cortex is a key
      patterning event and is achieved by the combined action of many proteins,
      including Pins, which itself is localized anteriorly. Here, a role is described
      for the trimeric G protein Go in the anterior localization of Numb and daughter
      cell fate specification. Go is shown to interact with Pins. In addition to a role
      in recruiting Numb to an asymmetric location in the cell's cortex, Go transduces
      a signal from the Frizzled receptor that directs the position in which the
      complex forms. Thus, Go likely integrates the signaling that directs the
      formation of the complex with the signaling that directs where the complex forms.

PMID- 16617105
TI  - Evidence for a role of developmental genes in the origin of obesity and body fat
      distribution.
AB  - Obesity, especially central obesity, is a hereditable trait associated with a
      high risk for development of diabetes and metabolic disorders. Combined gene
      expression analysis of adipocyte- and preadipocyte-containing fractions from
      intraabdominal and subcutaneous adipose tissue of mice revealed coordinated depot
      specific differences in expression of multiple genes involved in embryonic
      development and pattern specification. These differences were intrinsic and
      persisted during in vitro culture and differentiation. Similar depot-specific
      differences in expression of developmental genes were observed in human
      subcutaneous versus visceral adipose tissue. Furthermore, in humans, several
      genes exhibited changes in expression that correlated closely with body mass
      index and/or waist/hip ratio. Together, these data suggest that genetically
      programmed developmental differences in adipocytes and their precursors in
      different regions of the body play an important role in obesity, body fat
      distribution, and potential functional differences between internal and
      subcutaneous adipose tissue.

PMID- 16617106
TI  - Characterization of Su48, a centrosome protein essential for cell division.
AB  - The centrosome functions as the major microtubule-organizing center and plays a
      vital role in guiding chromosome segregation during mitosis. Centrosome
      abnormalities are frequently seen in a variety of cancers, suggesting that
      dysfunction of this organelle may contribute to malignant transformation. In our
      efforts to identify the protein components of the centrosome and to understand
      the structure features involved in the assembly and functions of this organelle,
      we cloned and characterized a centrosome-associated protein called Su48. We found
      that a coiled coil-containing subdomain of Su48 was both sufficient and required
      for its centrosome localization. In addition, this structure also modulates Su48
      dimerization. Moreover, ectopic expression of Su48 causes abnormal mitosis, and a
      mutant form of Su48 disrupts the localization of gamma-tubulin to the centrosome.
      Finally, by microinjection of an anti-Su48 antibody, we found that disruption of
      normal Su48 functions leads to mitotic failure, possibly due to centrosome
      defects or incomplete cytokinesis. Thus, Su48 represents a previously
      unrecognized centrosome protein that is essential for cell division. We speculate
      that Su48 abnormalities may cause aberrant chromosome segregation and may
      contribute to aneuploidy and malignant transformation.

PMID- 16617107
TI  - Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced
      vasodilation in mice and humans.
AB  - Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an
      adverse effect, termed flushing, which consists of cutaneous vasodilation with
      associated discomfort. An animal model of NA-induced flushing has been
      established in mice. As in humans, NA stimulated vasodilation in a dose-dependent
      manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2
      in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors
      have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2
      (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the
      DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce
      cutaneous vasodilation, and DP2-/- mice had a normal vasodilatory response to NA.
      By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and
      MK-0524, a DP1-selective antagonist, blocked both PGD2- and NA-induced
      vasodilation. NA-induced vasodilation was also studied in DP1+/+, DP1+/-, and DP1
      /- mice; although NA-induced vasodilation depended almost completely on DP1 in
      female mice, it depended only partially on DP1 in male mice. The residual NA
      induced vasodilation in male DP-/- mice was aspirin-sensitive. Thus, in the
      mouse, DP1 appears to be an important component involved in NA-induced
      vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved.
      A clinical study in healthy men and women demonstrated that treatment with MK
      0524 reduced the symptoms of flushing and the increase in skin perfusion after
      the administration of NA. These studies suggest that DP1 receptor antagonism may
      be an effective means to suppress NA-induced flushing in humans.

PMID- 16617108
TI  - Assessing the fidelity of the fossil record by using marine bivalves.
AB  - Taxa that fail to become incorporated into the fossil record can reveal much
      about the biases of this record and provide the information needed to correct
      such biases in empirical analyses of the history of life. Yet little is known
      about the characteristics of taxa missing from the fossil record. For the marine
      Bivalvia, which have become a model system for macroevolutionary and
      macroecological analysis in the fossil record, 308 of the 1,292 living genera and
      subgenera (herein termed "taxa") are not recorded as fossils. These missing taxa
      are not a random sample of the clade, but instead tend to have small body size,
      reactive shell structures, commensal or parasitic habit, deep-sea distribution,
      narrow geographic range, restriction to regions exposing few Neogene marine
      sediments, or recent date of formal taxonomic description in the neontological
      literature. Most missing taxa show two or more of these features and tend to be
      concentrated in particular families. When we exclude the smallest taxa (<1 cm)
      and deep-sea endemics, date of published description and geographic range become
      the strongest predictors of the missing taxa; other factors are statistically
      insignificant or have relatively small effects. These biases might influence a
      variety of analyses including the use of fossil data in support of phylogenetic
      analyses, molecular clock calibrations, and analyses of spatial and temporal
      dynamics of clades and biotas. Clade inventories such as these can be used to
      develop protocols that minimize the biases imposed by sampling and preservation.

PMID- 16617109
TI  - EM measurements define the dimensions of the "30-nm" chromatin fiber: evidence
      for a compact, interdigitated structure.
AB  - Chromatin structure plays a fundamental role in the regulation of nuclear
      processes such as DNA transcription, replication, recombination, and repair.
      Despite considerable efforts during three decades, the structure of the 30-nm
      chromatin fiber remains controversial. To define fiber dimensions accurately, we
      have produced very long and regularly folded 30-nm fibers from in vitro
      reconstituted nucleosome arrays containing the linker histone and with increasing
      nucleosome repeat lengths (10 to 70 bp of linker DNA). EM measurements show that
      the dimensions of these fully folded fibers do not increase linearly with
      increasing linker length, a finding that is inconsistent with two-start helix
      models. Instead, we find that there are two distinct classes of fiber structure,
      both with unexpectedly high nucleosome density: arrays with 10 to 40 bp of linker
      DNA all produce fibers with a diameter of 33 nm and 11 nucleosomes per 11 nm,
      whereas arrays with 50 to 70 bp of linker DNA all produce 44-nm-wide fibers with
      15 nucleosomes per 11 nm. Using the physical constraints imposed by these
      measurements, we have built a model in which tight nucleosome packing is achieved
      through the interdigitation of nucleosomes from adjacent helical gyres.
      Importantly, the model closely matches raw image projections of folded chromatin
      arrays recorded in the solution state by using electron cryo-microscopy.

PMID- 16617110
TI  - Phospholipase DZ2 plays an important role in extraplastidic galactolipid
      biosynthesis and phosphate recycling in Arabidopsis roots.
AB  - Low phosphate (Pi) availability is one of the major constraints for plant
      productivity in natural and agricultural ecosystems. Plants have evolved a myriad
      of developmental and biochemical mechanisms to increase internal Pi uptake and
      utilization efficiency. One important biochemical pathway leading to an increase
      in internal Pi availability is the hydrolysis of phospholipids. Hydrolyzed
      phospholipids are replaced by nonphosphorus lipids such as galactolipids and
      sulfolipids, which help to maintain the functionality and structure of membrane
      systems. Here we report that a member of the Arabidopsis phospholipase D gene
      family (PLDZ2) is gradually induced upon Pi starvation in both shoots and roots.
      From lipid content analysis we show that an Arabidopsis pldz2 mutant is defective
      in the hydrolysis of phospholipids and has a reduced capacity to accumulate
      galactolipids under limiting Pi conditions. Morphological analysis of the pldz2
      root system shows a premature change in root architecture in response to Pi
      starvation. These results show that PLDZ2 is involved in the eukaryotic
      galactolipid biosynthesis pathway, specifically in hydrolyzing
      phosphatidylcholine and phosphatidylethanolamine to produce diacylglycerol for
      digalactosyldiacylglycerol synthesis and free Pi to sustain other Pi-requiring
      processes.

PMID- 16617111
TI  - Posttranslational myristoylation of caspase-activated p21-activated protein
      kinase 2 (PAK2) potentiates late apoptotic events.
AB  - p21-activated protein kinase (PAK) 2 is a small GTPase-activated serine/threonine
      kinase regulating various cytoskeletal functions and is cleaved by caspase-3
      during apoptosis. We demonstrate that the caspase-cleaved PAK2 C-terminal kinase
      fragment (C-t-PAK2) is posttranslationally myristoylated, although myristoylation
      is typically a cotranslational process. Myristoylation and an adjacent polybasic
      domain of C-t-PAK2 are sufficient to redirect EGFP from the cytosol to membrane
      ruffles and internal membranes. Membrane localization and the ability of C-t-PAK2
      to induce cell death are significantly reduced when myristoylation is abolished.
      In addition, the proper myristoylation-dependent membrane localization of C-t
      PAK2 significantly increased signaling through the stress-activated c-Jun N
      terminal kinase signaling pathway, which often regulates apoptosis.
      Interestingly, C-t-PAK2 promoted cell death without compromising mitochondrial
      integrity. Posttranslational myristoylation of caspase-cleaved proteins involved
      in cytoskeletal dynamics (e.g., PAK2, actin, and gelsolin) might be part of a
      unique series of mechanisms involved in the regulation of the later events of
      apoptosis.

PMID- 16617112
TI  - Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate
      extrinsic factors in guiding MHC restriction.
AB  - The underlying basis of major histocompatibility complex (MHC) restriction is
      unclear. Nevertheless, current data suggest that a common thermodynamic signature
      dictates alphabeta T cell receptor (TcR) ligation. To evaluate whether this
      thermodynamic signature defines MHC restriction, we have examined the
      thermodynamic basis of a highly characterized immunodominant TcR interacting with
      its cognate peptide-MHC-I ligand. Surprisingly, we observed this interaction to
      be governed by favorable enthalpic and entropic forces, which is in contrast to
      the prevailing generality, namely, enthalpically driven interactions combined
      with markedly unfavorable entropic forces. We conclude that extrinsic molecular
      factors, such as coreceptor ligation, conformational adjustments involved in TcR
      signaling, or constraints dictated by higher-order arrangement of ligated TcRs,
      might play a greater role in guiding MHC restriction than appreciated previously.

PMID- 16617113
TI  - Multireplicon genome architecture of Lactobacillus salivarius.
AB  - Lactobacillus salivarius subsp. salivarius strain UCC118 is a bacteriocin
      producing strain with probiotic characteristics. The 2.13-Mb genome was shown by
      sequencing to comprise a 1.83 Mb chromosome, a 242-kb megaplasmid (pMP118), and
      two smaller plasmids. Megaplasmids previously have not been characterized in
      lactic acid bacteria or intestinal lactobacilli. Annotation of the genome
      sequence indicated an intermediate level of auxotrophy compared with other
      sequenced lactobacilli. No single-copy essential genes were located on the
      megaplasmid. However, contingency amino acid metabolism genes and carbohydrate
      utilization genes, including two genes for completion of the pentose phosphate
      pathway, were megaplasmid encoded. The megaplasmid also harbored genes for the
      Abp118 bacteriocin, a bile salt hydrolase, a presumptive conjugation locus, and
      other genes potentially relevant for probiotic properties. Two subspecies of L.
      salivarius are recognized, salivarius and salicinius, and we detected
      megaplasmids in both subspecies by pulsed-field gel electrophoresis of sizes
      ranging from 100 kb to 380 kb. The discovery of megaplasmids of widely varying
      size in L. salivarius suggests a possible mechanism for genome expansion or
      contraction to adapt to different environments.

PMID- 16617114
TI  - Monitoring chaperone engagement of substrates in the endoplasmic reticulum of
      live cells.
AB  - The folding environment in the endoplasmic reticulum (ER) depends on multiple
      abundant chaperones that function together to accommodate a range of substrates.
      The ways in which substrate engagement shapes either specific chaperone dynamics
      or general ER attributes in vivo remain unknown. In this study, we have evaluated
      how changes in substrate flux through the ER influence the diffusion of both the
      lectin chaperone calreticulin and an inert reporter of ER crowdedness. During
      acute changes in substrate load, the inert probe revealed no changes in ER
      organization, despite significant changes in calreticulin dynamics. By contrast,
      inhibition of the lectin chaperone system caused rapid changes in the ER
      environment that could be reversed over time by easing new substrate burden. Our
      findings provide insight into the normal organization and dynamics of an ER
      chaperone and characterize the capacity of the ER to maintain homeostasis during
      acute changes in chaperone activity and availability.

PMID- 16617115
TI  - ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents
      unique virulence determinant among bacterial pathogens.
AB  - Unlike many bacterial pathogens, Mycoplasma pneumoniae is not known to produce
      classical toxins, and precisely how M. pneumoniae injures the respiratory
      epithelium has remained a mystery for >50 years. Here, we report the
      identification of a virulence factor (MPN372) possibly responsible for airway
      cellular damage and other sequelae associated with M. pneumoniae infections in
      humans. We show that M. pneumoniae MPN372 encodes a 68-kDa protein that possesses
      ADP-ribosyltransferase (ART) activity. Within its N terminus, MPN372 contains key
      amino acids associated with NAD binding and ADP-ribosylating activity, similar to
      pertussis toxin (PTX) S1 subunit (PTX-S1). Interestingly, MPN372 ADP ribosylates
      both identical and distinct mammalian proteins when compared with PTX-S1.
      Remarkably, MPN372 elicits extensive vacuolization and ultimate cell death of
      mammalian cells, including distinct and progressive patterns of cytopathology in
      tracheal rings in organ culture that had been previously ascribed to infection
      with WT virulent M. pneumoniae. We observed dramatic seroconversion to MPN372 in
      patients diagnosed with M. pneumoniae-associated pneumonia, indicating that this
      toxin is synthesized in vivo and possesses highly immunogenic epitopes.

PMID- 16617116
TI  - Evidence on the chromosomal location of centromeric DNA in Plasmodium falciparum
      from etoposide-mediated topoisomerase-II cleavage.
AB  - Centromeres are the chromosomal loci that facilitate segregation, and, in most
      eukaryotes, they encompass extensive regions of genomic DNA. Topoisomerase-II has
      been identified as a crucial regulator of segregation in a wide range of
      organisms and exhibits premitotic accumulation at centromeres. Consistent with
      this property, treatment of cells with the topoisomerase-II inhibitor etoposide
      promotes chromosomal cleavage at sites within centromeric DNA. In the case of the
      human malaria parasite Plasmodium falciparum, despite a completed genome
      sequence, there are no experimental data on the nature of centromeres. To address
      this issue, we have used etoposide-mediated topoisomerase-II cleavage as a
      biochemical marker to map centromeric DNA on all 14 parasite chromosomes. We find
      that topoisomerase-II activity is concentrated at single chromosomal loci and
      that cleavage sites extend over approximately 10 kb. A shared feature of these
      topoisomerase-II cleavage sites is the presence of an extremely AT-rich (
      approximately 97%) domain with a strictly defined size limit of 2.3-2.5 kb.
      Repetitive arrays identified within the domains do not display interchromosomal
      conservation in terms of length, copy number, or sequence. These unusual
      properties suggest that P. falciparum chromosomes contain a class of "regional"
      centromere distinct from those described in other eukaryotes, including the human
      host.

PMID- 16617117
TI  - Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression
      without regulatory T cell development.
AB  - Forkhead winged-helix transcription factor Foxp3 serves as the dedicated mediator
      of the genetic program governing CD25+CD4+ regulatory T cell (T(R)) development
      and function in mice. In humans, its role in mediating T(R) development has been
      controversial. Furthermore, the fate of T(R) precursors in FOXP3 deficiency has
      yet to be described. Making use of flow cytometric detection of human FOXP3, we
      have addressed the relationship between FOXP3 expression and human T(R)
      development. Unlike murine Foxp3- T cells, a small subset of human CD4+ and CD8+
      T cells transiently up-regulated FOXP3 upon in vitro stimulation. Induced FOXP3,
      however, did not alter cell-surface phenotype or suppress T helper 1 cytokine
      expression. Furthermore, only ex vivo FOXP3+ T(R) cells persisted after prolonged
      culture, suggesting that induced FOXP3 did not activate a T(r) developmental
      program in a significant number of cells. FOXP3 flow cytometry was also used to
      further characterize several patients exhibiting symptoms of immune
      dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) with or
      without FOXP3 mutations. Most patients lacked FOXP3-expressing cells, further
      solidifying the association between FOXP3 deficiency and immune dysregulation,
      polyendocrinopathy, enteropathy, X-linked syndrome. Interestingly, one patient
      bearing a FOXP3 mutation enabling expression of stable FOXP3(mut) protein
      exhibited FOXP3(mut)-expressing cells among a subset of highly activated CD4+ T
      cells. This observation raises the possibility that the severe autoimmunity in
      FOXP3 deficiency can be attributed, in part, to aggressive T helper cells that
      have developed from T(R) precursors.

PMID- 16617118
TI  - Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes.
AB  - The mechanisms regulating activation of monocytes remain incompletely understood.
      Herein we provide evidence that Kruppel-like factor 2 (KLF2) inhibits
      proinflammatory activation of monocytes. In vitro, KLF2 expression in monocytes
      is reduced by cytokine activation or differentiation. Consistent with this
      observation, KLF2 expression in circulating monocytes is reduced in patients with
      chronic inflammatory conditions such as coronary artery disease. Adenoviral
      overexpression of KLF2 inhibits the LPS-mediated induction of proinflammatory
      factors, cytokines, and chemokines and reduces phagocytosis. Conversely, short
      interfering RNA-mediated reduction in KLF2 increased inflammatory gene
      expression. Reconstitution of immunodeficient mice with KLF2-overexpressing
      monocytes significantly reduced carrageenan-induced acute paw edema formation.
      Mechanistically, KLF2 inhibits the transcriptional activity of both NF-kappaB and
      activator protein 1, in part by means of recruitment of transcriptional
      coactivator p300/CBP-associated factor. These observations identify KLF2 as a
      novel negative regulator of monocytic activation.

PMID- 16617119
TI  - FZL, an FZO-like protein in plants, is a determinant of thylakoid and chloroplast
      morphology.
AB  - FZO is a dynamin-related membrane-remodeling protein that mediates fusion between
      mitochondrial outer membranes in animals and fungi. We identified a single FZO
      like protein in Arabidopsis, FZL, a new plant-specific member of the dynamin
      superfamily. FZL is targeted to chloroplasts and associated with thylakoid and
      envelope membranes as punctate structures. fzl knockout mutants have
      abnormalities in chloroplast and thylakoid morphology, including disorganized
      grana stacks and alterations in the relative proportions of grana and stroma
      thylakoids. Overexpression of FZL-GFP also conferred defects in thylakoid
      organization. Mutation of a conserved residue in the predicted FZL GTPase domain
      abolished both the punctate localization pattern and ability of FZL-GFP to
      complement the fzl mutant phenotype. FZL defines a new protein class within the
      dynamin superfamily of membrane-remodeling GTPases that regulates organization of
      the thylakoid network in plants. Notably, FZL levels do not affect mitochondrial
      morphology or ultrastructure, suggesting that mitochondrial morphology in plants
      is regulated by an FZO-independent mechanism.

PMID- 16617121
TI  - Methods of quantitative proteomics and their application to plant organelle
      characterization.
AB  - Many cell biologists wish to know the subcellular localization of proteins of
      interest. Proteomics methods have the potential to describe the entire protein
      content of organelles. However, practical limitations in organelle isolation and
      analysis of low abundance proteins have meant that organelle proteomics has had,
      until recently, only limited success. Some examples of quantitative proteomic
      methods and their use in the study of plant organelle proteomes are discussed
      here. It is concluded that 2D-difference gel electrophoresis (2D-DIGE) as well as
      differential isotope tagging strategies coupled to non-gel-based LC-MS are
      proving useful in this area of research.

PMID- 16617120
TI  - Distinct genetic interactions between multiple Vegf receptors are required for
      development of different blood vessel types in zebrafish.
AB  - Recent evidence indicates a specific role for vascular endothelial growth factor
      a (Vegfa) during artery development in both zebrafish and mouse embryos, whereas
      less is known about signals that govern vein formation. In zebrafish, loss of
      vegfa blocks segmental artery formation and reduces artery-specific gene
      expression, whereas veins are largely unaffected. Here, we describe a mutation in
      the zebrafish vegf receptor-2 homolog, kdra, which eliminates its kinase activity
      and leads to specific defects in artery development. We further find that Flt4, a
      receptor for Vegfc, cooperates with Kdr during artery morphogenesis, but not
      differentiation. We also identify an additional zebrafish vegfr-2 ortholog,
      referred to as kdrb, which can partially compensate for loss of kdra but is
      dispensable for vascular development in wild-type embryos. Interestingly, we find
      that these Vegf receptors are also required for formation of veins but in
      distinct genetic interactions that differ from those required for artery
      development. Taken together, our results indicate that formation of arteries and
      veins in the embryo is governed in part by different Vegf receptor combinations
      and suggest a genetic mechanism for generating blood vessel diversity during
      vertebrate development.

PMID- 16617122
TI  - Activation of endoplasmic reticulum stress response during the development of
      ischemic heart disease.
AB  - Endoplasmic reticulum (ER) stress has been found to be associated with
      neurodegenerative diseases and diabetes mellitus. Whether ER stress is involved
      in the development of heart disease is not known. Cardiac-specific expression of
      monocyte chemoattractant protein-1 (MCP-1) in mice causes the development of
      ischemic heart disease. Here we report that microarray analysis of gene
      expression changes in the heart of these transgenic mice revealed that a cluster
      of ER stress-related genes was transcriptionally activated in the heart during
      the development of ischemic heart disease. The gene array results were verified
      by quantitative real-time PCR that showed highly elevated transcript levels of
      genes involved in unfolded protein response such as ER and cytoplasmic
      chaperones, oxidoreductases, protein disulfide isomerase (PDI) family, and ER
      associated degradation system such as ubiquitin. Immunoblot analysis confirmed
      the expression of chaperones, PDI, and ubiquitin. Immunohistochemical analyses
      showed that ER stress proteins were associated mainly with the degenerating
      cardiomyocytes. A novel ubiquitin fold modifier (Ufm1) that has not been
      previously associated with ER stress and not found to be induced under any
      condition was also found to be upregulated in the hearts of MCP mice (transgenic
      mice that express MCP-1 specifically in the heart). The present results strongly
      suggest that activation of ER stress response is involved in the development of
      ischemic heart disease in this murine model.

PMID- 16617123
TI  - Restoring depressed HERG K+ channel function as a mechanism for insulin treatment
      of abnormal QT prolongation and associated arrhythmias in diabetic rabbits.
AB  - Abnormal QT prolongation (QT-P) in diabetic patients has become a nonnegligible
      clinical problem and has attracted increasing attention from basic scientists,
      because it increases the risk of lethal ventricular arrhythmias. Correction of QT
      P may be an important measure in minimizing sudden cardiac death in diabetic
      patients. Here we report the efficacy of insulin in preventing QT-P and the
      associated arrhythmias and the mechanisms underlying the effects in a rabbit
      model of type 1 insulin-dependent diabetes mellitus (IDDM). The heart rate
      corrected QT (QTc) interval and action potential duration were considerably
      prolonged, with frequent ventricular tachycardias. The rapid delayed rectifier K+
      current (IKr) was markedly reduced in IDDM hearts, and hyperglycemia depressed
      the function of the human ether-a-go-go-related gene (HERG), which conducts IKr.
      The impairment was primarily ascribed to the enhanced oxidative damage to the
      myocardium, as indicated by the increased intracellular level of reactive oxygen
      species and simultaneously decreased endogenous antioxidant reserve and by the
      increased lipid peroxidation and protein oxidation. Moreover, IDDM or
      hyperglycemia resulted in downregulation of HERG protein level. Insulin restored
      the depressed IKr/HERG and prevented QTc/action potential duration prolongation
      and the associated arrhythmias, and the beneficial actions of insulin are
      partially due to its antioxidant ability. Our study represents the first
      documentation of oxidative stress as the major metabolic mechanism for HERG K+
      dysfunction, which causes diabetic QT-P, and suggests IKr/HERG as a potential
      therapeutic target for treatment of the disorder.

PMID- 16617124
TI  - Sp3 inhibits Sp1-mediated activation of the cardiac troponin T promoter and is
      downregulated during pathological cardiac hypertrophy in vivo.
AB  - Combinatorial interactions between cis elements and trans-acting factors are
      required for regulation of cardiac gene expression during normal cardiac
      development and pathological cardiac hypertrophy. Sp factors bind GC boxes and
      are implicated in recruitment and assembly of the basal transcriptional complex.
      In this study, we show that the cardiac troponin T (cTnT) promoter contains a GC
      box that is necessary for basal and cAMP-mediated activity of cTnT promoter
      constructs transfected in embryonic cardiomyocytes. Cardiac nuclear proteins bind
      the cTnT GC box in a sequence-specific fashion and consist of Sp1, Sp2, and Sp3
      protein factors. By chromatin immunoprecipitation, Sp1 binds the cTnT promoter
      "in vivo." Cotransfected Sp1 trans-activates the cTnT promoter in cardiomyocytes
      in culture. Sp3 represses Sp1-mediated transcriptional activation of the cTnT
      gene in embryonic cardiomyocytes. Sp3 repression of Sp1-mediated cTnT promoter
      activation is dose dependent, inferring a mechanism of competitive
      binding/inhibition. To evaluate the role of Sp factors in cardiac gene expression
      in vivo, we have established a clinically relevant animal model of pathological
      cardiac hypertrophy where the fetal cardiac program is activated. In this animal
      model, cardiac hypertrophy results from increased left-right shunting, volume
      loading of the left ventricle, and pressure loading of the right ventricle. Sp1
      expression is increased in all four hypertrophied cardiac chambers, whereas Sp3
      expression is diminished. This observation is consistent with the in vitro
      activating function of Sp1 and inhibitory effects of Sp3 on activity of cTnT
      promoter constructs. Sp factor levels are modulated during the hypertrophic
      cardiac program in vivo.

PMID- 16617125
TI  - Redox regulation of endogenous substrate oxidation by cardiac mitochondria.
AB  - Reactive oxygen species (ROS) play important roles in regulating mitochondrial
      function, as well as in ischemia-reperfusion injury and cardioprotection. Here we
      show that, in the absence of exogenous substrates, cardiac mitochondria have a
      surprisingly large capacity to phosphorylate ADP by oxidizing endogenous
      substrates, provided that H2O2 is removed from the extramitochondrial environment
      and a reduced environment is maintained in the matrix. In isolated mitochondria
      without exogenous substrates, addition of catalase and the membrane-permeant
      reducing agent N-acetylcysteine (Nac) or the ROS scavenger mercaptopropionyl
      glycine significantly increased the ability to phosphorylate added ADP, as
      demonstrated by 1) full recovery of membrane potential (Deltapsi) and matrix
      volume from ADP-induced dissipation and shrinkage, 2) ADP-dependent increase in
      O2 consumption, and 3) enhanced rate of ATP synthesis. Removal of
      extramitochondrial H2O2 by catalase was required to stimulate endogenous
      substrate oxidation, as shown by the increase in O2 consumption and Deltapsi.
      This effect was greatly enhanced by addition of Nac or mercaptopropionyl glycine
      to suppress oxidation-induced ROS increases in the matrix. Theoretical
      considerations, as well as reversible inhibition of O2 consumption with 3
      mercaptopropionic acid and pyruvate in state 3, indicate that these substrates
      are fatty acids. Under in vivo conditions in which powerful antioxidant
      conditions are maintained, this mechanism may be important in stimulation of beta
      oxidation and ATP production at low levels of extramitochondrial fatty acids.
      Incapacitation of this mechanism may potentially contribute to mitochondrial
      dysfunction during oxidative stress.

PMID- 16617126
TI  - Cardioprotective mechanisms of Prunus cerasus (sour cherry) seed extract against
      ischemia-reperfusion-induced damage in isolated rat hearts.
AB  - The effects of kernel extract obtained from sour cherry (Prunus cerasus) seed on
      the postischemic cardiac recovery were studied in isolated working rat hearts.
      Rats were treated with various daily doses of the extract for 14 days, and hearts
      were then isolated and subjected to 30 min of global ischemia followed by 120 min
      of reperfusion. The incidence of ventricular fibrillation (VF) and tachycardia
      (VT) fell from their control values of 92% and 100% to 50% (not significant) and
      58% (not significant), 17% (P<0.05), and 25% (P<0.05) with the doses of 10 mg/kg
      and 30 mg/kg of the extract, respectively. Lower concentrations of the extract (1
      and 5 mg/kg) failed to significantly reduce the incidence of VF and VT during
      reperfusion. Sour cherry seed kernel extract (10 and 30 mg/kg) significantly
      improved the postischemic recovery of cardiac function (coronary flow, aortic
      flow, and left ventricular developed pressure) during reperfusion. We have also
      demonstrated that the extract-induced protection in cardiac function
      significantly reflected in a reduction of infarct size. Immunohistochemistry
      indicates that a reduction in caspase-3 activity and apoptotic cells by the
      extract, beside other potential action mechanisms of proanthocyanidin, trans
      resveratrol, and flavonoid components of the extract, could be responsible for
      the cardioprotection in ischemic-reperfused myocardium.

PMID- 16617127
TI  - Protective effects of epoxyeicosatrienoic acids on human endothelial cells from
      the pulmonary and coronary vasculature.
AB  - Epoxyeicosatrienoic acids (EETs) are cytochrome P-450 (CYP) metabolites
      synthesized from the essential fatty acid arachidonic acid to generate four
      regioisomers, 14,15-, 11,12-, 8,9-, and 5,6-EET. Cultured human coronary artery
      endothelial cells (HCAECs) contain endogenous EETs that are increased by
      stimulation with physiological agonists such as bradykinin. Because EETs are
      known to modulate a number of vascular functions, including angiogenesis, we
      tested each of the four regioisomers to characterize their effects on survival
      and apoptosis of HCAECs and cultured human lung microvascular endothelial cells
      (HLMVECs). A single application of physiologically relevant concentration of
      14,15-, 11,12-, and 8,9-EET but not 5,6-EET (0.75-300 nM) promoted concentration
      dependent increase in cell survival of HLMVECs and HCAECs after removal of serum.
      The lipids also protected the same cells from death via the intrinsic, as well as
      extrinsic, pathways of apoptosis. EETs did not increase intracellular calcium
      concentration ([Ca2+]i) or phosphorylate mitogen-activated protein kinase p44/42
      when applied to these cells, and their protective action was attenuated by the
      phosphotidylinositol-3 kinase inhibitor wortmannin (10 microM) but not the
      cyclooxygenase inhibitor indomethacin (20 microM). Our results demonstrate for
      the first time the capacity of EETs to enhance human endothelial cell survival by
      inhibiting both the intrinsic, as well as extrinsic, pathways of apoptosis, an
      important underlying mechanism that may promote angiogenesis and endothelial
      survival during atherosclerosis and related cardiovascular ailments.

PMID- 16617128
TI  - Thyroid hormone downregulates the expression and function of sarcoplasmic
      reticulum-associated CaM kinase II in the rabbit heart.
AB  - Phosphorylation of sarcoplasmic reticulum (SR) Ca2+-cycling proteins by a
      membrane-associated Ca2+/calmodulin-dependent protein kinase II (CaM kinase II)
      is a well-documented physiological mechanism for regulation of transmembrane Ca2+
      fluxes and the cardiomyocyte contraction-relaxation cycle. The present study
      investigated the effects of L-thyroxine-induced hyperthyroidism on protein
      expression of SR CaM kinase II and its substrates, endogenous CaM kinase II
      mediated SR protein phosphorylation, and SR Ca2+ pump function in the rabbit
      heart. Membrane vesicles enriched in junctional SR (JSR) or longitudinal SR (LSR)
      isolated from euthyroid and hyperthyroid rabbit hearts were utilized. Endogenous
      CaM kinase II-mediated phosphorylation of ryanodine receptor-Ca2+ release channel
      (RyR-CRC), Ca2+-ATPase, and phospholamban (PLN) was significantly lower (30-70%)
      in JSR and LSR vesicles from hyperthyroid than from euthyroid rabbit heart.
      Western immunoblotting analysis revealed significantly higher (approximately 40%)
      levels of sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) in JSR, but
      not in LSR, from hyperthyroid than from euthyroid rabbit heart. Maximal velocity
      of Ca2+ uptake was significantly increased in JSR (130%) and LSR (50%) from
      hyperthyroid compared with euthyroid rabbit hearts. Apparent affinity of the Ca2+
      ATPase for Ca2+ did not differ between the two groups. Protein levels of PLN and
      CaM kinase II were significantly lower (30-40%) in JSR, LSR, and ventricular
      tissue homogenates from hyperthyroid rabbit heart. These findings demonstrate
      selective downregulation of expression and function of CaM kinase II in
      hyperthyroid rabbit heart in the face of upregulated expression and function of
      SERCA2 predominantly in the JSR compartment.

PMID- 16617129
TI  - Disruption of COX-2 modulates gene expression and the cardiac injury response to
      doxorubicin.
AB  - To determine the role of cyclooxygenase (COX)-2 in anthracycline-induced cardiac
      toxicity, we administered doxorubicin (Dox) to mice with genetic disruption of
      COX-2 (COX-2-/-). After treatment with Dox, COX-2-/- mice had increased cardiac
      dysfunction and cardiac cell apoptosis compared with Dox-treated wild-type mice.
      The expression of the death-associated protein kinase-related apoptosis-inducing
      protein kinase-2 was also increased in Dox-treated COX-2-/- animals. The altered
      gene expression, cardiac injury, and dysfunction after Dox treatment in COX-2-/-
      mice was attenuated by a stable prostacyclin analog, iloprost. Wild-type mice
      treated with Dox developed cardiac fibrosis that was absent in COX-2-/- mice and
      unaffected by iloprost. These results suggest that genetic disruption of COX-2
      increases the cardiac dysfunction after treatment with Dox by an increase in
      cardiac cell apoptosis. This Dox-induced cardiotoxicity in COX-2-/- mice was
      attenuated by a prostacyclin analog, suggesting a protective role for
      prostaglandins in this setting.

PMID- 16617130
TI  - Exercise training improves aging-induced downregulation of VEGF angiogenic
      signaling cascade in hearts.
AB  - Exercise training improves aging-induced deterioration of angiogenesis in the
      heart. However, the mechanisms underlying exercise-induced improvement of
      capillary density in the aged heart are unclear. Vascular endothelial growth
      factor (VEGF) is implicated in angiogenesis, which activated angiogenic signaling
      cascade through Akt and endothelial nitric oxide synthase (eNOS)-related pathway.
      We hypothesized that VEGF angiogenic signaling cascade in the heart contributes
      to a molecular mechanism of exercise training-induced improvement of capillary
      density in old age. With the use of hearts of sedentary young rats (4 mo old),
      sedentary aged rats (23 mo old), and exercise-trained aged rats (23 mo old, swim
      training for 8 wk), the present study investigated whether VEGF and VEGF-related
      angiogenic molecular expression in the aged heart is affected by exercise
      training. Total capillary density in the heart was significantly lower in the
      sedentary aged rats compared with the sedentary young rats, whereas that in the
      exercise-trained rat was significantly higher than the sedentary aged rats. The
      mRNA and protein expressions of VEGF and of fms-like tyrosine kinase-1 (Flt-1)
      and fetal liver kinase-1 (Flk-1), which are main VEGF receptors, in the heart
      were significantly lower in the sedentary aged rats compared with the sedentary
      young rats, whereas those in the exercise-trained rats were significantly higher
      than those in the sedentary aged rats. The phosphorylation of Akt protein and
      eNOS protein in the heart corresponded to the changes in the VEGF protein levels.
      These findings suggest that exercise training improves aging-induced
      downregulation of cardiac VEGF angiogenic signaling cascade, thereby contributing
      to the exercise training-induced improvement of angiogenesis in old age.

PMID- 16617131
TI  - Chronic systemic delivery of angiopoietin-2 reveals a possible independent
      angiogenic effect.
AB  - Angiopoietin-2 has been implicated in the angiogenic response; however, this
      response has been tied to the expression of VEGF, and an independent angiogenic
      role has yet to be described. In this report, we detail the generation of
      transgenic mice that conditionally express angiopoietin-2 in the liver, resulting
      in sustained increases in circulating levels. These animals survive gestation and
      present with several vascular abnormalities, including an increase in the
      diameter of myocardial coronary vessels and a reduction in the density of
      endocardial vessels. In the lung, prominent increases in vessel diameter were
      observed. These vascular remodeling changes occurred in the absence of any
      apparent increase in VEGF expression. Our results illustrate that chronic
      systemic delivery of angiopoietin-2 induces angiogenesis in the absence of
      increased VEGF expression and that angiopoietin-2 promotes myocardial coronary
      vessel remodeling.

PMID- 16617132
TI  - Autonomic regulation of pacemaker activity: role of heart nitric oxide synthases.
AB  - In autonomic-blocked rats treated with NG-nitro-L-arginine methyl ester (L-NAME,
      7.5 mg/kg), heart rate increased 18% and mean arterial pressure increased 48%.
      Thyroidectomy, along with autonomic blockade, hampered the chronotropic response
      but did not modify the effect on blood pressure. After 150 min of autonomic
      blockade, the experimental end point, total nitric oxide (NO) production by heart
      NO synthases (NOS) decreased 61%: from 54 to 21 nmol NO.min-1.g heart-1.
      Mitochondrial NOS (mtNOS) and sarcoplasmic reticulum endothelial NOS activities
      decreased 74% and 52%, respectively. Mitochondria isolated from whole heart
      showed a well-coupled oxidative phosphorylation with high respiratory control and
      ADP-to-O ratios, decreased mtNOS activity (55-60%), and decreased mtNOS protein
      expression (70%). Immunohistochemistry with anti-inducible NOS antibody linked to
      gold particles localized mtNOS at the inner mitochondrial membranes.
      Histochemical right atrial NOS (NADPH-diaphorase) decreased 55% after heart
      denervation. The effects of autonomic denervation on the NO system were partially
      prevented by thyroidectomy performed simultaneously with autonomic blockade.
      Western blot analysis indicated a very rapid mtNOS protein turnover (half
      time=120 min) with a process of protein expression that was upregulated by
      thyroidectomy and a degradation process that was downregulated by the autonomic
      nervous system. The observations suggest that NO-mediated pathways contribute to
      pacemaker heart activity, likely through the NO steady-state levels in the right
      atrium and the whole heart.

PMID- 16617133
TI  - Neutrophil activation is modulated by sex hormones after trauma-hemorrhagic shock
      and burn injuries.
AB  - Recent literature indicates that females are more resistant to shock-, trauma-,
      and sepsis-induced immune dysfunction and organ injury than are males.
      Consequently, using trauma-hemorrhagic shock (T/HS) and burn models, we tested
      whether the neutrophil response to trauma occurred in a sexually dimorphic
      fashion and, if so, the role of sex hormones. Neutrophil activation, as reflected
      by CD11b expression and respiratory burst activity, was increased to a greater
      extent in male rats than in female rats after T/HS or burn injury. Testosterone
      appeared to potentiate neutrophil activation, because castration reduced
      neutrophil activation, whereas ovariectomy had little effect. Mechanistically,
      this sexually dimorphic neutrophil response appeared to be due to both cellular
      and humoral factors. Evidence for a cellular difference between male and female
      neutrophils is based on the observation that naive female neutrophils were more
      resistant to activation by burn or T/HS plasma and lymph than naive male
      neutrophils and that this resistance varied over the estrus cycle. Additionally,
      the humoral environment was more neutrophil activating in male rats, because burn
      and T/HS plasma and lymph from male rats activated naive male neutrophils to a
      greater extent than comparable samples from females. Last, on the basis of in
      vitro experiments examining the effects of estrogen on calcium signaling, it
      appears that estrogen limits trauma-induced neutrophil activation, at least in
      part, by limiting the entry of calcium into the cell via store-operated calcium
      entry mechanisms. In conclusion, there is a striking sexual dimorphism in
      neutrophil responses after trauma, and these changes reflect both cellular
      resistance to activation as well as a less activating humoral environment.

PMID- 16617134
TI  - Does hyperglycemia reduce proliferation or increase apoptosis?

PMID- 16617135
TI  - Inward rectifying potassium channels facilitate cell-to-cell communication in
      hamster retractor muscle feed arteries.
AB  - This study examined whether inward rectifying K+ (KIR) channels facilitate cell
      to-cell communication along skeletal muscle resistance arteries. With the use of
      feed arteries from the hamster retractor muscle, experiments examined whether KIR
      channels were functionally expressed and whether channel blockade attenuated the
      conduction of acetylcholine-induced vasodilation, an index of cell-to-cell
      communication. Consistent with KIR channel expression, this study observed the
      following: 1) a sustained Ba2+-sensitive, K+-induced dilation in preconstricted
      arteries; 2) a Ba2+-sensitive inwardly rectifying K+ current in arterial smooth
      muscle cells; and 3) KIR2.1 and KIR2.2 expression in the smooth muscle layer of
      these arteries. It was subsequently shown that the discrete application of
      acetylcholine elicits a vasodilation that conducts with limited decay along the
      feed artery wall. In the presence of 100 microM Ba2+, the local and conducted
      response to acetylcholine was attenuated, a finding consistent with a role for
      KIR in facilitating cell-to-cell communication. A computational model of vascular
      communication accurately predicted these observations. Control experiments
      revealed that in contrast to Ba2+, ATP-sensitive- and large-conductance Ca2+
      activated-K+ channel inhibitors had no effect on the local or conducted
      vasodilatory response to acetylcholine. We conclude that smooth muscle KIR
      channels play a key role in facilitating cell-to-cell communication along
      skeletal muscle resistance arteries. We attribute this facilitation to the
      intrinsic property of negative slope conductance, a biophysical feature common to
      KIR2.1- and 2.2-containing channels, which enables them to increase their
      activity as a cell hyperpolarizes.

PMID- 16617136
TI  - Engineered early embryonic cardiac tissue retains proliferative and contractile
      properties of developing embryonic myocardium.
AB  - Embryonic myocardium has a high rate of cell proliferation and regulates cellular
      proliferation, contractile function, and myocardial architecture in response to
      changes in external mechanical loads. However, the small and complex three
      dimensional (3D) structure of the embryonic myocardium limits our ability to
      directly investigate detailed relationships between mechanical load, contractile
      function, and cardiomyocyte proliferation. We developed a novel 3D engineered
      early embryonic cardiac tissue (EEECT) from early embryonic ventricular cells to
      test the hypothesis that EEECT retains the proliferative and contractile
      properties of embryonic myocardium. We combined freshly isolated White Leghorn
      chicken embryonic ventricular cells at Hamburger-Hamilton (HH) stage 31 (day 7 of
      a 46-stage, 21-day incubation period), collagen type I, and matrix factors to
      construct cylindrical-shaped EEECTs. We studied tissue architecture, cell
      proliferation patterns, and contractile function. We then generated engineered
      fetal cardiac tissue (EFCT) from HH stage 40 (day 14) fetal ventricular cells for
      direct comparison with EEECT. Tissue architecture was similar in EEECT and EFCT.
      EEECT maintained high cell proliferation patterns by culture day 12, whereas EFCT
      decreased cell proliferation rate by culture day 9 (P < 0.05). EEECT increased
      active contractile force from culture day 7 to day 12. The culture day 12 EEECT
      contractile response to the beta-adrenergic stimulation was less than culture day
      9 EFCT (P < 0.05). Cyclic mechanical stretch stimulation induced myocardial
      hyperplasia in EEECT. Results indicate that EEECT retains the proliferative and
      contractile properties of developing embryonic myocardium and shows potential as
      a robust in vitro model of developing embryonic myocardium.

PMID- 16617137
TI  - Pulsatile blood flow in the entire coronary arterial tree: theory and experiment.
AB  - The pulsatility of coronary circulation can be accurately simulated on the basis
      of the measured branching pattern, vascular geometry, and material properties of
      the coronary vasculature. A Womersley-type mathematical model is developed to
      analyze pulsatile blood flow in diastole in the absence of vessel tone in the
      entire coronary arterial tree on the basis of previously measured morphometric
      data. The model incorporates a constitutive equation of pressure and cross
      section area relation based on our previous experimental data. The formulation
      enables the prediction of the impedance, the pressure distribution, and the
      pulsatile flow distribution throughout the entire coronary arterial tree. The
      model is validated by experimental measurements in six diastolic arrested,
      vasodilated porcine hearts. The agreement between theory and experiment is
      excellent. Furthermore, the present pulse wave results at low frequency agree
      very well with previously published steady-state model. Finally, the phase angle
      of flow is seen to decrease along the trunk of the major coronary artery and
      primary branches toward the capillary vessels. This study represents the first,
      most extensive validated analysis of Womersley-type pulse wave transmission in
      the entire coronary arterial tree down to the first segment of capillaries. The
      present model will serve to quantitatively test various hypotheses in the
      coronary circulation under pulsatile flow conditions.

PMID- 16617138
TI  - Novel role for K+-dependent Na+/Ca2+ exchangers in regulation of cytoplasmic free
      Ca2+ and contractility in arterial smooth muscle.
AB  - Cytoplasmic free Ca2+ ([Ca2+]cyt) is essential for the contraction and relaxation
      of blood vessels. The role of plasma membrane Na+/Ca2+ exchange (NCX) activity in
      the regulation of vascular Ca2+ homeostasis was previously ascribed to the NCX1
      protein. However, recent studies suggest that a relatively newly discovered K+
      dependent Na+/Ca2+ exchanger, NCKX (gene family SLC24), is also present in
      vascular smooth muscle. The purpose of the present study was to identify the
      expression and function of NCKX in arteries. mRNA encoding NCKX3 and NCKX4 was
      demonstrated by RT-PCR and Northern blot in both rat mesenteric and aortic smooth
      muscle. NCXK3 and NCKX4 proteins were also demonstrated by immunoblot and
      immunofluorescence. After voltage-gated Ca2+ channels, store-operated Ca2+
      channels, and Na+ pump were pharmacologically blocked, when the extracellular Na+
      was replaced with Li+ (0 Na+) to induce reverse mode (Ca2+ entry) activity of
      Na+/Ca2+ exchangers, a large increase in [Ca2+]cyt signal was observed in primary
      cultured aortic smooth muscle cells. About one-half of this [Ca2+]cyt signal
      depended on the extracellular K+. In addition, after the activity of NCX was
      inhibited by KB-R7943, Na+ replacement-induced Ca2+ entry was absolutely
      dependent on extracellular K+. In arterial rings denuded of endothelium, a
      significant fraction of the phenylephrine-induced and nifedipine-resistant aortic
      or mesenteric contraction could be prevented by removal of extracellular K+.
      Taken together, these data provide strong evidence for the expression of NCKX
      proteins in the vascular smooth muscle and their novel role in mediating agonist
      stimulated [Ca2+]cyt and thereby vascular tone.

PMID- 16617139
TI  - A polymerized bovine hemoglobin oxygen carrier preserves regional myocardial
      function and reduces infarct size after acute myocardial ischemia.
AB  - The purpose of this study was to test if HBOC-201, a hemoglobin-based oxygen
      carrying solution, can decrease infarct size (or Inf) during acute, severe
      myocardial ischemia and reperfusion. To test the impact of HBOC-201 on infarct
      size, ischemia was produced in 18 dogs by coronary stenosis to achieve 80-95%
      flow reduction for 195 min along with pacing 10% above the spontaneous heart
      rate, followed by 180 min of reperfusion. Animals were randomized to intravenous
      infusion of HBOC-201 (1 g/kg) (n=6), normal saline (NS) (n=6), or phenylephrine
      (Phe) (n=6, as a control for the increased blood pressure seen with HBOC-201),
      given 15 min after the start of ischemia. Amount of infarct was quantified as the
      ratio between area at risk (AAR) and Inf after Evans blue and 2,3,5
      triphenyltetrazolium chloride staining. Hearts were divided into five layers from
      base (layer A) to apex (layer E) and photographed for digital image analysis of
      AAR and Inf. Regional myocardial function (RMF) was also measured after 60 min of
      ischemia and 15 min of reperfusion. Inf/AAR was significantly reduced after HBOC
      201 therapy (4.4+/-2.2%) vs. NS (26.0+/-3.6%) and Phe (25.7+/-4.1%) (both,
      P<0.05). RMF after reperfusion was restored to 92% of baseline with HBOC-201
      compared with 11% of baseline after NS (P<0.05) and 49% after Phe (P=not
      significant). HBOC-201 administration after induction of severe myocardial
      ischemia by acute coronary stenosis reduces infarct size and improves myocardial
      viability.

PMID- 16617140
TI  - Sodium current function in adult and aged canine atrial cells.
AB  - The incidence of atrial fibrillation increases with age, but it is unknown
      whether there are changes in the intrinsic function of Na+ currents in cells of
      the aged atria. Thus, we studied right (RA) and left (LA) atrial cells from two
      groups of dogs, adult and aged (>8 yr), to determine the change in Na+ currents
      with age. In this study all dogs were in normal sinus rhythm. Whole cell voltage
      clamp techniques were used to compare the Na+ currents in the two cell groups.
      Immunocytochemical studies were completed for the Na+ channel protein Na(v)1.5 to
      determine whether there was structural remodeling of this protein with age. In
      cells from aged animals, we found that Na+ currents are similar to those we
      measured in adult atria. However, Na+ current (I(Na)) density of the aged atria
      differed depending on the atrial chamber with LA cell currents being larger than
      RA cell currents. Thus with age, the difference in I(Na) density between atrial
      chambers remains. I(Na) kinetic differences between aged and adult cells included
      a significant acceleration into the inactivated state and an enhanced use
      dependent decrease in peak current in aged RA cells. Finally, there is no
      structural remodeling of the cardiac Na+ channel protein Na(v)1.5 in the aged
      atrial cell. In conclusion, with age there is no change in I(Na) density, but
      there are subtle kinetic differences contributing to slight enhancement of use
      dependence. There is no structural remodeling of the fast Na+ current protein
      with age.

PMID- 16617141
TI  - Cardiac fibroblasts: friend or foe?
AB  - Cardiac function is determined by the dynamic interaction of various cell types
      and the extracellular matrix that composes the heart. This interaction varies
      with the stage of development and the degree and duration of mechanical,
      chemical, and electrical signals between the various cell types and the ECM.
      Understanding how these complex signals interact at the molecular, cellular, and
      organ levels is critical to understanding the function of the heart under a
      variety of physiological and pathophysiological conditions. Quantitative
      approaches, both in vivo and in vitro, are essential to understand the dynamic
      interaction of mechanical, chemical, and electrical stimuli that govern cardiac
      function. The fibroblast can thus be a friend in normal function or a foe in
      pathophysiological conditions.

PMID- 16617142
TI  - A real-time PCR-based method for determining the surface coverage of thiol-capped
      oligonucleotides bound onto gold nanoparticles.
AB  - Here we report a real-time PCR-based method for determining the surface coverage
      of dithiol-capped oligonucleotides bound onto gold nanoparticles alone and in
      tandem with antibody. The detection of gold nanoparticle-bound DNA is
      accomplished by targeting the oligonucleotide with primer and probe binding
      sites, amplification of the oligonucleotide by PCR, and real-time measurement of
      the fluorescence emitted during the reaction. This method offers a wide dynamic
      range and is not dependant on the dissociation of the oligonucleotide strands
      from the gold nanoparticle surface; the fluorophore is not highly quenched by the
      gold nanoparticles in solution during fluorescence measurements. We show that
      this method and a fluorescence-based method give equivalent results for
      determining the surface coverage of oligonucleotides bound onto 13 or 30 nm gold
      nanoparticles alone and in tandem with antibody. Quantifying the surface coverage
      of immobilized oligonucleotides on metallic nanoparticle surfaces is important
      for optimizing the sensitivity of gold nanoparticle-based detection methods and
      for better understanding the interactions between thiol-functionalized
      oligonucleotides and gold nanoparticles.

PMID- 16617143
TI  - Algorithm for automatic genotype calling of single nucleotide polymorphisms using
      the full course of TaqMan real-time data.
AB  - Single nucleotide polymorphisms (SNPs) are often determined using TaqMan real
      time PCR assays (Applied Biosystems) and commercial software that assigns
      genotypes based on reporter probe signals at the end of amplification.
      Limitations to the large-scale application of this approach include the need for
      positive controls or operator intervention to set signal thresholds when one
      allele is rare. In the interest of optimizing real-time PCR genotyping, we
      developed an algorithm for automatic genotype calling based on the full course of
      real-time PCR data. Best cycle genotyping algorithm (BCGA), written in the open
      source language R, is based on the assumptions that classification depends on the
      time (cycle) of amplification and that it is possible to identify a best
      discriminating cycle for each SNP assay. The algorithm is unique in that it
      classifies samples according to the behavior of blanks (no DNA samples), which
      cluster with heterozygous samples. This method of classification eliminates the
      need for positive controls and permits accurate genotyping even in the absence of
      a genotype class, for example when one allele is rare. Here, we describe the
      algorithm and test its validity, compared to the standard end-point method and to
      DNA sequencing.

PMID- 16617144
TI  - Substituent effects on the pairing and polymerase recognition of simple unnatural
      base pairs.
AB  - As part of an effort to develop stable and replicable unnatural base pairs, we
      have evaluated a large number of unnatural nucleotides with predominantly
      hydrophobic nucleobases. Despite its limited aromatic surface area, a nucleobase
      analog scaffold that has emerged as being especially promising is the simple
      phenyl ring. Modifications of this scaffold with methyl and fluoro groups have
      been shown to impact base pair stability and polymerase recognition, suggesting
      that nucleobase shape, hydrophobicity and electrostatics are important. To
      further explore the impact of heteroatom substitution within this nucleobase
      scaffold, we report the synthesis, stability and polymerase recognition of
      nucleoside analogs bearing single bromo- or cyano-derivatized phenyl rings. Both
      modifications are found to generally stabilize base pair formation to a greater
      extent than methyl or fluoro substitution. Moreover, polymerase recognition of
      the unnatural base pairs is found to be very sensitive to both the position and
      nature of the heteroatom substituent. The results help identify the determinants
      of base pair stability and efficient replication and should contribute to the
      effort to develop stable and replicable unnatural base pairs.

PMID- 16617145
TI  - Novel link between E2F1 and Smac/DIABLO: proapoptotic Smac/DIABLO is
      transcriptionally upregulated by E2F1.
AB  - Deregulated expression of E2F1 not only promotes S-phase entry but also induces
      apoptosis. Although it has been well documented that E2F1 is able to induce p53
      dependent apoptosis via raising ARF activity, the mechanism by which E2F induces
      p53-independent apoptosis remains unclear. Here we report that E2F1 can directly
      bind to and activate the promoter of Smac/DIABLO, a mitochondrial proapoptotic
      gene, through the E2F1-binding sites BS2 (-542 approximately -535 bp) and BS3 (
      200 approximately -193 bp). BS2 and BS3 appear to be utilized in combination
      rather than singly by E2F1 in activation of Smac/DIABLO. Activation of BS2 and
      BS3 are E2F1-specific, since neither E2F2 nor E2F3 is able to activate BS2 or
      BS3. Using the H1299 ER-E2F1 cell line where E2F1 activity can be conditionally
      induced, E2F1 has been shown to upregulate the Smac/DIABLO expression at both
      mRNA and protein levels upon 4-hydroxytamoxifen treatment, resulting in an
      enhanced mitochondria-mediated apoptosis. Reversely, reducing the Smac/DIABLO
      expression by RNA interference significantly diminishes apoptosis induced by
      E2F1. These results may suggest a novel mechanism by which E2F1 promotes p53
      independent apoptosis through directly regulating its downstream mitochondrial
      apoptosis-inducing factors, such as Smac/DIABLO.

PMID- 16617146
TI  - dUTPase activity is critical to maintain genetic stability in Saccharomyces
      cerevisiae.
AB  - We identified a viable allele (dut1-1) of the DUT1 gene that encodes the dUTPase
      activity in Saccharomyces cerevisiae. The Dut1-1 protein possesses a single amino
      acid substitution (Gly82Ser) in a conserved motif nearby the active site and
      exhibits a greatly reduced dUTPase activity. The dut1-1 single mutant exhibits
      growth delay and cell cycle abnormalities and shows a strong spontaneous mutator
      phenotype. All phenotypes of the dut1-1 mutant are suppressed by the simultaneous
      inactivation of the uracil DNA N-glycosylase, Ung1. However, the ung1 dut1-1
      double mutant accumulates uracil in its genomic DNA. The viability of the dut1-1
      mutant is greatly impaired by the simultaneous inactivation of AP endonucleases.
      These data strongly suggest that the phenotypes of the dut1-1 mutant result from
      the incorporation of dUMPs into DNA subsequently converted into AP sites. The
      analysis of the dut1-1 strain mutation spectrum showed that cytosines are
      preferentially incorporated in front of AP sites in a Rev3-dependent manner
      during translesion synthesis. These results point to a critical role of the Dut1
      protein in the maintenance of the genetic stability. Therefore, the normal
      cellular metabolism, and not only its byproducts, is an important source of
      endogenous DNA damage and genetic instability in eukaryotic cells.

PMID- 16617147
TI  - Identification and characterization of mitochondrial abasic (AP)-endonuclease in
      mammalian cells.
AB  - Abasic (AP)-endonuclease (APE) is responsible for repair of AP sites, and single
      strand DNA breaks with 3' blocking groups that are generated either spontaneously
      or during repair of damaged or abnormal bases via the DNA base excision repair
      (BER) pathway in both nucleus and mitochondria. Mammalian cells express only one
      nuclear APE, 36 kDa APE1, which is essential for survival. Mammalian
      mitochondrial (mt) BER enzymes other than mtAPE have been characterized. In order
      to identify and characterize mtAPE, we purified the APE activity from beef liver
      mitochondria to near homogeneity, and showed that the mtAPE which has 3-fold
      higher specific activity relative to APE1 is derived from the latter with
      deletion of 33 N-terminal residues which contain the nuclear localization signal.
      The mtAPE-sized product could be generated by incubating 35S-labeled APE1 with
      crude mitochondrial extract, but not with cytosolic or nuclear extract,
      suggesting that cleavage of APE1 by a specific mitochondria-associated N-terminal
      peptidase is a prerequisite for mitochondrial import. The low abundance of mtAPE,
      particularly in cultured cells might be the reason for its earlier lack of
      detection by western analysis.

PMID- 16617148
TI  - Snail1 transcriptional repressor binds to its own promoter and controls its
      expression.
AB  - The product of Snail1 gene is a transcriptional repressor of E-cadherin
      expression and an inductor of the epithelial-mesenchymal transition in several
      epithelial tumour cell lines. Transcription of Snail1 is induced when epithelial
      cells are forced to acquire a mesenchymal phenotype. In this work we demonstrate
      that Snail1 protein limits its own expression: Snail1 binds to an E-box present
      in its promoter (at -146 with respect to the transcription start) and represses
      its activity. Therefore, mutation of the E-box increases Snail1 transcription in
      epithelial and mesenchymal cells. Evidence of binding of ectopic or endogenous
      Snail1 to its own promoter was obtained by chromatin immunoprecipitation (ChIP)
      experiments. Studies performed expressing different forms of Snail1 under the
      control of its own promoter demonstrate that disruption of the regulatory loop
      increases the cellular levels of Snail protein. These results indicate that
      expression of Snail1 gene can be regulated by its product and evidence the
      existence of a fine-tuning feed-back mechanism of regulation of Snail1
      transcription.

PMID- 16617149
TI  - A supersecondary structure library and search algorithm for modeling loops in
      protein structures.
AB  - We present a fragment-search based method for predicting loop conformations in
      protein models. A hierarchical and multidimensional database has been set up that
      currently classifies 105,950 loop fragments and loop flanking secondary
      structures. Besides the length of the loops and types of bracing secondary
      structures the database is organized along four internal coordinates, a distance
      and three types of angles characterizing the geometry of stem regions. Candidate
      fragments are selected from this library by matching the length, the types of
      bracing secondary structures of the query and satisfying the geometrical
      restraints of the stems and subsequently inserted in the query protein framework
      where their fit is assessed by the root mean square deviation (r.m.s.d.) of stem
      regions and by the number of rigid body clashes with the environment. In the
      final step remaining candidate loops are ranked by a Z-score that combines
      information on sequence similarity and fit of predicted and observed phi/psi main
      chain dihedral angle propensities. Confidence Z-score cut-offs were determined
      for each loop length that identify those predicted fragments that outperform a
      competitive ab initio method. A web server implements the method, regularly
      updates the fragment library and performs prediction. Predicted segments are
      returned, or optionally, these can be completed with side chain reconstruction
      and subsequently annealed in the environment of the query protein by conjugate
      gradient minimization. The prediction method was tested on artificially prepared
      search datasets where all trivial sequence similarities on the SCOP superfamily
      level were removed. Under these conditions it is possible to predict loops of
      length 4, 8 and 12 with coverage of 98, 78 and 28% with at least of 0.22, 1.38
      and 2.47 A of r.m.s.d. accuracy, respectively. In a head-to-head comparison on
      loops extracted from freshly deposited new protein folds the current method
      outperformed in a approximately 5:1 ratio an earlier developed database search
      method.

PMID- 16617150
TI  - Selective degradation of reverse gyrase and DNA fragmentation induced by
      alkylating agent in the archaeon Sulfolobus solfataricus.
AB  - Reverse gyrase is a peculiar DNA topoisomerase, specific of hyperthermophilic
      Archaea and Bacteria, which has the unique ability of introducing positive
      supercoiling into DNA molecules. Although the function of the enzyme has not been
      established directly, it has been suggested to be involved in DNA protection and
      repair. We show here that the enzyme is degraded after treatment of Sulfolobus
      solfataricus cells with the alkylating agent MMS. MMS-induced reverse gyrase
      degradation is highly specific, since (i) neither hydroxyurea (HU) nor puromycin
      have a similar effect, and (ii) topoisomerase VI and two chromatin components are
      not degraded. Reverse gyrase degradation does not depend on protein synthesis.
      Experiments in vitro show that direct exposure of cell extracts to MMS does not
      induce reverse gyrase degradation; instead, extracts from MMS-treated cells
      contain some factor(s) able to degrade the enzyme in extracts from control cells.
      In vitro, degradation is blocked by incubation with divalent metal chelators,
      suggesting that reverse gyrase is selectively degraded by a metal-dependent
      protease in MMS-treated cells. In addition, we find a striking concurrence of
      extensive genomic DNA degradation and reverse gyrase loss in MMS-treated cells.
      These results support the hypothesis that reverse gyrase plays an essential role
      in DNA thermoprotection and repair in hyperthermophilic organisms.

PMID- 16617151
TI  - Ciliary neural trophic factor: mimicking leptin's effects in skeletal muscle?

PMID- 16617152
TI  - Intranasal leptin: blood-brain barrier bypass (BBBB) for obesity?

PMID- 16617153
TI  - The elemental importance of sufficient iodine intake: a trace is not enough.

PMID- 16617154
TI  - Insulin-like growth factor binding protein-3: insulin-like growth factor
      independence comes of age.

PMID- 16617156
TI  - Counterpoint: developing a clinical pathology curriculum to meet current and
      future needs.

PMID- 16617157
TI  - C1q and MBL, components of the innate immune system, influence monocyte cytokine
      expression.
AB  - It has recently been recognized that the innate immune response, the powerful
      first response to infection, has significant influence in determining the nature
      of the subsequent adaptive immune response. C1q, mannose-binding lectin (MBL),
      and other members of the defense collagen family of proteins are pattern
      recognition molecules, able to enhance the phagocytosis of pathogens, cellular
      debris, and apoptotic cells in vitro and in vivo. Humans deficient in C1q
      inevitably develop a lupus-like autoimmune disorder, and studies in C1q knockout
      mice demonstrate a deficiency in the clearance of apoptotic cells with a
      propensity for autoimmune responses. The data presented here show that under
      conditions in which phagocytosis is enhanced, C1q and MBL modulate cytokine
      production at the mRNA and protein levels. Specifically, these recognition
      molecules of the innate immune system contribute signals to human peripheral
      blood mononuclear cells, leading to the suppression of lipopolysaccharide-induced
      proinflammatory cytokines, interleukin (IL)-1alpha and IL-1beta, and an increase
      in the secretion of cytokines IL-10, IL-1 receptor antagonist, monocyte
      chemoattractant protein-1, and IL-6. These data support the hypothesis that
      defense collagen-mediated suppression of a proinflammatory response may be an
      important step in the avoidance of autoimmunity during the clearance of apoptotic
      cells.

PMID- 16617158
TI  - TNF induces distinct gene expression programs in microvascular and macrovascular
      human endothelial cells.
AB  - The relevance of the diversity of endothelial cells (ECs) for the response to
      inflammatory stimuli is currently not well defined. Using oligonucleotide
      microarray technique, we systematically analyzed the tumor necrosis factor (TNF)
      induced expression profile in human microvascular ECs (HMEC) and macrovascular
      human umbilical vein ECs (HUVEC), analyzing 13,000 human genes by microarray
      analysis. Using strict inclusion and exclusion criteria, microarray analysis
      revealed that about half of the TNF-induced genes were specific for HMEC-1 or
      HUVEC. The microarray data could widely be confirmed by quantitative reverse
      transcriptase-polymerase chain reaction and at the protein level. It is
      interesting that the majority of those genes regulated depending on the cell type
      encoded for chemokines, cytokines, and cell surface molecules. Our results argue
      for a more careful consideration of specific effects restricted to distinct
      subtypes of ECs. The establishment of EC type-specific expression patterns may
      thus provide the basis for a selective manipulation of specific endothelial
      subtypes in different inflammatory diseases.

PMID- 16617159
TI  - The tissue pentraxin PTX3 limits C1q-mediated complement activation and
      phagocytosis of apoptotic cells by dendritic cells.
AB  - Pentraxins (PTX) and complement belong to the humoral arm of the innate immune
      system and have essential functions in immune defense to microbes and in
      scavenging cellular debris. The prototypic long PTX, PTX3, and the first
      component of the classical complement pathway, C1q, are innate opsonins involved
      in the disposal of dying cells by phagocytes. Whether the interaction between
      various innate opsonins impacts on their function is not fully understood. We
      show here that characterized Toll-like receptor (TLR) ligands elicit the
      production of C1q and PTX3 by immature dendritic cells (DC). Moreover, these
      molecules bind to dying cells with similar kinetics, although they recognize
      different domains on the cell membranes. PTX3 binds in the fluid phase to C1q,
      decreasing C1q deposition and subsequent complement activation on apoptotic
      cells. C1q increases the phagocytosis of apoptotic cells by DC and the release of
      interleukin-12 in the presence of TLR4 ligands and apoptotic cells; PTX3 inhibits
      both events. Moreover, PTX3 inhibited the cross-presentation of the MELAN
      A/melanoma antigen-reactive T cell 1 (MART-1) tumor antigen expressed by dying
      cells, even in the presence of C1q. These results suggest that interaction of C1q
      and PTX3 influences the clearance of apoptotic cells by DC. The coordinated
      induction by primary, proinflammatory signals of C1q and PTX3 and their
      reciprocal regulation during inflammation influences the clearance of apoptotic
      cells by antigen-presenting cells and possibly plays a role in immune
      homeostasis.

PMID- 16617161
TI  - Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site
      directed mutagenesis: amino acid residues responsible for species-based
      difference of CYP24A1 between humans and rats.
AB  - Our previous studies revealed the species-based difference of CYP24A1-dependent
      vitamin D metabolism. Although human CYP24A1 catalyzes both C-23 and C-24
      oxidation pathways, rat CYP24A1 shows almost no C-23 oxidation pathway. We tried
      to identify amino acid residues that cause the species-based difference by site
      directed mutagenesis. In the putative substrate-binding regions, amino acid
      residue of rat CYP24A1 was converted to the corresponding residue of human
      CYP24A1. Among eight mutants examined, T416M and I500T showed C-23 oxidation
      pathway. In addition, the mutant I500F showed quite a different metabolism of
      1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] from both human and rat CYP24A1.
      These results strongly suggest that the amino acid residues at positions 416 and
      500 play a crucial role in substrate binding and greatly affect substrate
      orientation. A three-dimensional model of CYP24A1 indicated that the A-ring and
      triene part of 1alpha,25(OH)2D3 could be located close to amino acid residues at
      positions 416 and 500, respectively. Our findings provide useful information for
      the development of new vitamin D analogs for clinical use.

PMID- 16617160
TI  - Pivotal Advance: eosinophil infiltration of solid tumors is an early and
      persistent inflammatory host response.
AB  - Tumor-associated eosinophilia has been observed in numerous human cancers and
      several tumor models in animals; however, the details surrounding this
      eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma
      cell injection model to demonstrate that eosinophil infiltration of tumors
      occurred from the earliest palpable stages with significant accumulations only in
      the necrotic and capsule regions. Furthermore, the presence of diffuse
      extracellular matrix staining for eosinophil major basic protein was restricted
      to the necrotic areas of tumors, indicating that eosinophil degranulation was
      limited to this region. Antibody-mediated depletion of CD4+ T cells and adoptive
      transfer of eosinophils suggested, respectively, that the accumulation of
      eosinophils is not associated with T helper cell type 2-dependent immune
      responses and that recruitment is a dynamic, ongoing process, occurring
      throughout tumor growth. Ex vivo migration studies have identified what appears
      to be a novel chemotactic factor(s) released by stressed/dying melanoma cells,
      suggesting that the accumulation of eosinophils in tumors occurs, in part,
      through a unique mechanism dependent on a signal(s) released from areas of
      necrosis. Collectively, these studies demonstrate that the infiltration of tumors
      by eosinophils is an early and persistent response that is spatial-restricted. It
      is more important that these data also show that the mechanism(s) that elicit
      this host response occur, independent of immune surveillance, suggesting that
      eosinophils are part of an early inflammatory reaction at the site of
      tumorigenesis.

PMID- 16617162
TI  - Transfection of drug-specific T-cell receptors into hybridoma cells: tools to
      monitor drug interaction with T-cell receptors and evaluate cross-reactivity to
      related compounds.
AB  - In the context of drug hypersensitivity, our group has recently proposed a new
      model based on the structural features of drugs (pharmacological interaction with
      immune receptors; p-i concept) to explain their recognition by T cells. According
      to this concept, even chemically inert drugs can stimulate T cells because
      certain drugs interact in a direct way with T-cell receptors (TCR) and possibly
      major histocompatibility complex molecules without the need for metabolism and
      covalent binding to a carrier. In this study, we investigated whether mouse T
      cell hybridomas transfected with drug-specific human TCR can be used as an
      alternative to drug-specific T-cell clones (TCC). Indeed, they behaved like TCC
      and, in accordance with the p-i concept, the TCR recognize their specific drugs
      in a direct, processing-independent, and dose-dependent way. The presence of
      antigen-presenting cells was a prerequisite for interleukin-2 production by the
      TCR-transfected cells. The analysis of cross-reactivity confirmed the fine
      specificity of the TCR and also showed that TCR transfectants might provide a
      tool to evaluate the potential of new drugs to cause hypersensitivity due to
      cross-reactivity. Recombining the alpha- and beta-chains of sulfanilamide- and
      quinolone-specific TCR abrogated drug reactivity, suggesting that both original
      alpha- and beta-chains were involved in drug binding. The TCR-transfected
      hybridoma system showed that the recognition of two important classes of drugs
      (sulfanilamides and quinolones) by TCR occurred according to the p-i concept and
      provides an interesting tool to study drug-TCR interactions and their biological
      consequences and to evaluate the cross-reactivity potential of new drugs of the
      same class.

PMID- 16617163
TI  - The role of human nucleoside transporters in cellular uptake of 4'-thio-beta-D
      arabinofuranosylcytosine and beta-D-arabinosylcytosine.
AB  - 4'-Thio-beta-D-arabinofuranosyl cytosine (TaraC) is in phase I development for
      treatment of cancer. In human equilibrative nucleoside transporter (hENT) 1
      containing CEM cells, initial rates of uptake (10 microM; picomoles per
      microliter of cell water per second) of [3H]TaraC and [3H]1-beta-D
      arabinofuranosyl cytosine (araC) were low (0.007 +/- 003 and 0.034 +/- 0.003,
      respectively) compared with that of [3H]uridine (0.317 +/- 0.048), a highactivity
      hENT1 permeant. In hENT1- and hENT2-containing HeLa cells, initial rates of
      uptake (10 microM; picomoles per cell per second) of [3H]TaraC, [3H]araC, and
      [3H]deoxycytidine were low (0.30 +/- 0.003, 0.42 +/- 0.03, and 0.51 +/- 0.11,
      respectively) and mediated primarily by hENT1 (approximately 74, approximately
      65, and approximately 61%, respectively). In HeLa cells with recombinant human
      concentrative nucleoside transporter (hCNT) 1 or hCNT3 and pharmacologically
      blocked hENT1 and hENT2, transport of 10 microM[3H]TaraC and [3H]araC was not
      detected. The apparent affinities of recombinant transporters (produced in yeast)
      for a panel of cytosine-containing nucleosides yielded results that were
      consistent with the observed low-permeant activities of TaraC and araC for
      hENT1/2 and negligible permeant activities for hCNT1/2/3. During prolonged drug
      exposures of CEM cells with hENT1 activity, araC was more cytotoxic than TaraC,
      whereas coexposures with nitrobenzylthioinosine (to pharmacologically block
      hENT1) yielded identical cytotoxicities for araC and TaraC. The introduction by
      gene transfer of hENT2 and hCNT1 activities, respectively, into nucleoside
      transport-defective CEM cells increased sensitivity to both drugs moderately and
      slightly. These results demonstrated that nucleoside transport capacity
      (primarily via hENT1, to a lesser extent by hENT2 and possibly by hCNT1) is a
      determinant of pharmacological activity of both drugs.

PMID- 16617164
TI  - Rescue of p53 blockage by the A(2A) adenosine receptor via a novel interacting
      protein, translin-associated protein X.
AB  - Blockage of the p53 tumor suppressor has been found to impair nerve growth factor
      (NGF)-induced neurite outgrowth in PC-12 cells. We report herein that such
      impairment could be rescued by stimulation of the A(2A) adenosine receptor (A(2A)
      R), a G protein-coupled receptor implicated in neuronal plasticity. The A(2A)-R
      mediated rescue occurred in the presence of protein kinase C (PKC) inhibitors or
      protein kinase A (PKA) inhibitors and in a PKA-deficient PC-12 variant. Thus,
      neither PKA nor PKC was involved. In contrast, expression of a truncated A(2A)-R
      mutant harboring the seventh transmembrane domain and its C terminus reduced the
      rescue effect of A(2A)-R. Using the cytoplasmic tail of the A(2A)-R as bait, a
      novel-A(2A)-R-interacting protein [translin-associated protein X (TRAX)] was
      identified in a yeast two-hybrid screen. The authenticity of this interaction was
      verified by pull-down experiments, coimmunoprecipitation, and colocalization of
      these two molecules in the brain. It is noteworthy that reduction of TRAX using
      an antisense construct suppressed the rescue effect of A(2A)-R, whereas
      overexpression of TRAX alone caused the same rescue effect as did A(2A)-R
      activation. Results of [(3)H]thymidine and bromodeoxyuridine incorporation
      suggested that A(2A)-R stimulation inhibited cell proliferation in a TRAX
      dependent manner. Because the antimitotic activity is crucial for NGF function,
      the A(2A)-R might exert its rescue effect through a TRAX-mediated
      antiproliferative signal. This antimitotic activity of the A(2A)-R also enables a
      mitogenic factor (epidermal growth factor) to induce neurite outgrowth. We
      demonstrate that the A(2A)-R modulates the differentiation ability of trophic
      factors through a novel interacting protein, TRAX.

PMID- 16617165
TI  - Novel alpha1-adrenergic receptor signaling pathways: secreted factors and
      interactions with the extracellular matrix.
AB  - alpha1-Adrenergic receptor (alpha1-ARs) subtypes (alpha1A, alpha1B, and alpha1D)
      regulate multiple signal pathways, such as phospholipase C, protein kinase C
      (PKC), and mitogen-activated protein kinases. We employed oligonucleotide
      microarray technology to explore the effects of both short- (1 h) and long-term
      (18 h) activation of the alpha1A-AR to enable RNA changes to occur downstream of
      earlier well characterized signaling pathways, promoting novel couplings.
      Polymerase chain reaction (PCR) studies confirmed that PKC was a critical
      regulator of alpha1A-AR-mediated gene expression, and secreted interleukin (IL)-6
      also contributed to gene expression alterations. We next focused on two novel
      signaling pathways that might be mediated through alpha1A-AR stimulation because
      of the clustering of gene expression changes for cell adhesion/motility (syndecan
      4 and tenascin-C) and hyaluronan (HA) signaling. We confirmed that alpha1-ARs
      induced adhesion in three cell types to vitronectin, an interaction that was also
      integrin-, FGF7-, and PKC-dependent. alpha1-AR activation also inhibited cell
      migration, which was integrin- and PKC-independent but still required secretion
      of FGF7. alpha1-AR activation also increased the expression and deposition of HA,
      a glycosaminoglycan, which displayed two distinct structures: pericellular coats
      and long cable structures, as well as increasing expression of the HA receptor,
      CD44. Long cable structures of HA can bind leukocytes, which this suggests that
      alpha1-ARs may be involved in proinflammatory responses. Our results indicate
      alpha1-ARs induce the secretion of factors that interact with the extracellular
      matrix to regulate cell adhesion, motility and proinflammatory responses through
      novel signaling pathways.

PMID- 16617166
TI  - The anti-inflammatory drug, nimesulide (4-nitro-2-phenoxymethane-sulfoanilide),
      uncouples mitochondria and induces mitochondrial permeability transition in human
      hepatoma cells: protection by albumin.
AB  - Like other nonsteroidal anti-inflammatory drugs, nimesulide (4-nitro-2
      phenoxymethane-sulfoanilide) triggers hepatitis in a few recipients. Although
      nimesulide has been shown to uncouple mitochondrial respiration and cause
      hepatocyte necrosis in the absence of albumin, mechanisms for cell death are
      incompletely understood, and comparisons with human concentrations are difficult
      because 99% of nimesulide is albumin-bound. We studied the effects of nimesulide,
      with or without a physiological concentration of albumin, in isolated rat liver
      mitochondria or microsomes and in human hepatoma cells. Nimesulide did not
      undergo monoelectronic nitro reduction in microsomes. In mitochondria incubated
      without albumin, nimesulide (50 microM) decreased the mitochondrial membrane
      potential (DeltaPsim), increased basal respiration, and potentiated the
      mitochondrial permeability transition (MPT) triggered by calcium preloading. In
      HUH-7 cells incubated for 24 h without albumin, nimesulide (1 mM) decreased the
      DeltaPsim and cell NADPH and increased the glutathione disulfide/reduced
      glutathione ratio and cell peroxides; nimesulide triggered MPT, ATP depletion,
      high cell calcium, and caused mostly necrosis, with rare apoptotic cells.
      Coincubation with either cyclosporin A (an MPT inhibitor) or the combination of
      fructose-1,6-diphosphate (a glycolysis substrate) and oligomycin (an ATPase
      inhibitor) prevented the decrease in DeltaPsim, ATP depletion, and cell death. A
      physiological concentration of albumin abolished the effects of nimesulide on
      isolated mitochondria or HUH-7 cells. In conclusion, the weak acid, nimesulide,
      uncouples mitochondria and triggers MPT and ATP depletion in isolated
      mitochondria or hepatoma cells incubated without albumin. However, in the
      presence of albumin, only a fraction of the drug enters cells or organelles, and
      uncoupling and toxicity are not observed.

PMID- 16617167
TI  - Protein kinase C delta mediates platelet-induced breast cancer cell invasion.
AB  - Platelets play an important role in carcinogenesis, but the underlying molecular
      mechanisms remain poorly understood. To investigate the effects of platelets on
      in vitro invasion of MCF7 human breast cancer cells, human MCF7 cells were used
      to study their interactions with platelets using aggregometry and cell invasion
      chambers. Zymography and quantitative polymerase chain reaction (PCR) were used
      to study matrix metalloproteinases (MMPs), whereas Western blot was used to study
      protein kinase C (PKC) delta in MCF7 cells. We observed that platelets promoted
      invasion of MCF7 cells (3-fold increase, p<0.05, n=3) and that this process
      correlated with a dramatic increase in MMP-9 (8 fold-increase, p<0.001, n=3),
      which is known to facilitate cancer cell invasion. Because both platelets and
      MCF7 cells have been shown to release MMP-9, we investigated the cellular source
      that accounted for this increase. The time course and the use of specific protein
      synthesis inhibitors demonstrated that most of the increase in MMP-9 levels
      derived from de novo synthesis of this protease by cancer cells. Furthermore,
      platelets activated PKCdelta in MCF7 cells after 1 h of incubation (18.45+/-4.75%
      increase, p<0.05, n=4-7), which, in turn, led to an up-regulation of MMP-9 mRNA
      (from 60+/-20 to 1040+/-100 pg, p<0.001, n=3) and protein levels (18-fold
      increase, p<0.001, n=3), with the subsequent cell invasion-promoting effects.
      PKCdelta plays a crucial role in transducing the invasion-promoting effects of
      platelets in breast cancer cells, and the specific inhibition of PKCdelta may be
      a strategy to decrease platelet-mediated cancer cell invasion.

PMID- 16617168
TI  - Improved left ventricular function and reduced necrosis after myocardial
      ischemia/reperfusion in rabbits treated with ranolazine, an inhibitor of the late
      sodium channel.
AB  - Ranolazine is an inhibitor of the late sodium current and, via this mechanism,
      decreases sodium-dependent intracellular calcium overload during ischemia and
      reperfusion. Ranolazine reduces angina, but there is little information on its
      effects in acute myocardial infarction. The aim of this study was to test the
      effects of ranolazine on left ventricular (LV) function and myocardial infarct
      size after ischemia/reperfusion in rabbits. Ten minutes before coronary artery
      occlusion (CAO), anesthetized rabbits were assigned to vehicle (n=15) or
      ranolazine (2 mg/kg i.v. bolus plus 60 microg/kg/min i.v. infusion; n=15). Hearts
      received 60 min of CAO and 3 h of reperfusion. CAO caused LV dysfunction
      associated with necrosis. However, at the end of reperfusion, rabbits treated
      with ranolazine had better global LV ejection fraction (0.42+/-0.02 versus 0.33+/
      0.02; p<0.007) and stroke volume (1.05+/-0.08 versus 0.78+/-0.07 ml; p<0.01)
      compared with vehicle. The fraction of the LV wall that was akinetic or
      dyskinetic was significantly less in the ranolazine group at 0.23+/-0.03 versus
      0.34+/-0.03 in vehicle-treated group; p<0.02. The ischemic risk region was
      similar in both groups; however, infarct size was significantly smaller in the
      treated group (44+/-5 versus 57+/-4% vehicle; p<0.04). There were no significant
      differences among groups in heart rate, arterial pressure, LV end-diastolic
      pressure, or maximum-positive or -negative first time derivative of LV pressure
      (dP/dt). In conclusion, the results of this study show that ranolazine provides
      protection during acute myocardial infarction in this rabbit model of
      ischemia/reperfusion. Ranolazine treatment led to better ejection fraction,
      stroke volume and less wall motion abnormality after reperfusion, and less
      myocardial necrosis.

PMID- 16617169
TI  - Murder in Ciudad Juarez: A parable of women's struggle for human rights.
AB  - The murder of hundreds of women in Ciudad Juarez during the past decade has
      compelled women to mobilize. This mobilization is a parable of women's struggle
      for human rights because the factors that cause gender-based violence in Mexico
      are common throughout the world, the authorities' failure to punish those crimes
      constitutes a form of gender discrimination that is prevalent throughout the
      world, and the imperative for Mexican women to mobilize in defense of their own
      human rights is shared by women throughout the world. This struggle involves a
      double transformation: the transformation of women's organizations into human
      rights organizations and the transformation of human rights advocacy through the
      integration of the gender perspective.

PMID- 16617170
TI  - Dating aggression, sexual coercion, and aggression-supporting attitudes among
      college men as a function of participation in aggressive high school sports.
AB  - Aggressive male sports have been criticized as bastions of sexism and training
      grounds for aggression against women, but there have been few empirical
      demonstrations of these alleged relationships. The authors studied self-reported
      dating aggression and sexual coercion in 147 college men. Men who had
      participated in aggressive high school sports, as compared with other men,
      engaged in more psychological aggression, physical aggression, and sexual
      coercion toward their dating partners, caused their partners more physical
      injury, were more accepting of violence, had more sexist attitudes and hostility
      toward women, were more accepting of rape myths, and were less tolerant of
      homosexuality. Results indicate that participation in aggressive high school
      sports is one of the multiple developmental pathways leading to relationship
      violence.

PMID- 16617171
TI  - The impact of sexual abuse in the lives of young women involved or at risk of
      involvement with the juvenile justice system.
AB  - Girls in the juvenile justice system have high rates of past sexual abuse. To
      better understand the relationship between sexual abuse and justice system
      involvement, we analyzed survey interviews with 169 young women involved or at
      risk of involvement with juvenile justice, comparing girls who experienced sexual
      abuse with those who did not. Girls experiencing sexual abuse had more negative
      mental health, school, substance use, risky sexual behavior, and delinquency
      outcomes. These findings highlight a need for interventions to assist girls who
      have experienced abuse and efforts to prevent abuse and improve child welfare and
      social service systems.

PMID- 16617172
TI  - Responding in their best interests: Contextualizing women's coping with
      acquaintance sexual aggression.
AB  - Using an investigation of 202 college women who completed a survey about coping
      with sexual aggression from a known male assailant, the authors examined
      assailant behaviors, along with women's victimization history, alcohol use,
      positive relationship expectancies, and sexual assertiveness, to clarify how
      these factors shape women's responses to acquaintance sexual aggression.
      Multivariate regression analyses showed that these factors and assailant actions
      accounted uniquely and cumulatively for women's responding. Rape avoidance and
      resistance training programs can benefit by using a two-pronged approach: by
      targeting factors that impede and promote women's assertion and by helping women
      anticipate and respond to assailant actions.

PMID- 16617173
TI  - The phenomenology of meditation for female survivors of intimate partner
      violence.
AB  - An existential-phenomenological methodology was utilized to investigate the
      experience of meditation for female survivors of intimate partner violence. Six
      coresearchers were taught a form of concentrative meditation and were asked to
      meditate daily and to attend a weekly group meditation for 6 weeks.
      Semistructured interviews were utilized to gather the data. The essence of the
      experience that was revealed was the emergence of a centered awareness that is
      distinctly different from the usual mode of being in the world. Findings suggest
      the value of meditation as an intervention strategy with survivors and
      demonstrate the need for further research in this area.

PMID- 16617174
TI  - The Ile128Thr polymorphism influences stability and ligand binding properties of
      the microsomal triglyceride transfer protein.
AB  - The microsomal triglyceride transfer protein (MTTP) is essential for the assembly
      of VLDLs. We recently observed that a polymorphism in the MTTP promoter (
      493G>T), which is in allelic association with an isoleucine-to-theronine
      substitution at position 128 (Ile128Thr) in the expressed protein, confers an
      increased risk of coronary heart disease. Two variant proteins comprising amino
      acids 16-297 of intact MTTP, MTTP(N)-Ile128 and MTTP(N)-Thr128, had similar
      native secondary structure content, as judged by circular dichroism. However, the
      thermal stability of MTTP(N)-Thr128 was greatly reduced, and this protein was
      also more extensively cleaved in limited proteolysis experiments compared with
      MTTP(N)-Ile128; both of these findings support a less compact fold. On adding
      LDL, which includes natively folded apolipoprotein B (apoB), decreased stability
      of the MTTP(N)-Thr128-LDL complex was observed compared with that of the MTTP(N)
      Ile128-LDL complex. In a refined model of the N-terminal domain of MTTP, residue
      128 is located in a surface-exposed position, in the same region as an identified
      MTTP binding site in the homologous apoB protein. Thus, the Ile128Thr
      polymorphism confers reduced structural stability, leading to decreased binding
      of MTTP to LDL particles. Because the major MTTP binding target on LDL is apoB,
      the Ile128Thr polymorphism could target the MTTP-apoB interaction.

PMID- 16617175
TI  - Mapping the gates. Focus on "Relationship between physiological response type (RA
      and SA) and vibrissal receptive field of neurons within the rat trigeminal
      ganglion".

PMID- 16617176
TI  - Effect of background colors on the tuning of color-selective cells in monkey area
      V4.
AB  - When objects are viewed in different illuminants, their color does not change or
      changes little in spite of significant changes in the wavelength composition of
      the light reflected from them. In previous studies, we have addressed the
      physiology underlying this color constancy by recording from cells in areas V1,
      V2, and V4 of the anesthetized monkey. Truly color-coded cells, ones that respond
      to a patch of a given color irrespective of the wavelength composition of the
      light reflected from it, were only found in area V4. In the present study, we
      have used a different approach to test the responses of V4 cells in both
      anesthetized and awake behaving monkeys. Stimuli of different colors, embedded
      within a Mondrian-type multicolored background, were used to identify the
      chromatic selectivity of neurons. The illumination of the background was then
      varied, and the tuning of V4 neurons was tested again for each background
      illumination. With anesthetized monkeys, the psychophysical effect of changing
      background illumination was inferred from our own experience, whereas in the
      awake behaving animal, it was directly reported by the monkey. We found that the
      majority of V4 neurons shifted their color-tuning profile with each change in the
      background illumination: each time the color of the background on the computer
      screen was changed so as to simulate a change in illumination, cells shifted
      their color-tuning function in the direction of the chromaticity component that
      had been increased. A similar shift was also observed in colored match-to-sample
      psychometric functions of both human and monkey. The shift in monkey psychometric
      functions was quantitatively equivalent to the shift in the responses of the
      corresponding population of cells. We conclude that neurons in area V4 exhibit
      the property of color constancy and that their response properties are thus able
      to reflect color perception.

PMID- 16617177
TI  - Expression of a functional hyperpolarization-activated current (Ih) in the mouse
      nucleus reticularis thalami.
AB  - The GABAergic neurons of the nucleus reticularis thalami (nRT) express the type 2
      hyperpolarization-activated cAMP-sensitive (HCN2) subunit mRNA, but surprisingly,
      they were reported to lack the hyperpolarization-activated (Ih) current carried
      by this subunit. Using the voltage-clamp recordings in the thalamocortical slice
      preparation of the newborn and juvenile mice (P6-P23), we demonstrate that, in
      the presence of 1 mM barium (Ba2+), the nRT neurons express a slow
      hyperpolarization-activated inward current, suggesting that the Ih is present but
      masked in control conditions by K+ leak currents. We investigate the identity of
      the hyperpolarization-activated current in the nRT by studying its physiological
      and pharmacological profile in presence of Ba2+. We show that it has voltage- and
      time-dependent properties typical of the Ih, that it is blocked by cesium and
      ZD7288, two blockers of the Ih, and that it is carried both by the K+ and Na+
      ions. We could also alter the gating characteristics of the hyperpolarization
      activated current in the nRT by adding a nonhydrolysable analogue of cAMP to the
      pipette solution. Finally, using the current-clamp recording, we showed that
      blocking the hyperpolarization-activated current induced an hyperpolarization
      correlated with an increase of the R(in) of the nRT neurons. In conclusion, our
      results demonstrate that the nRT neurons express the Ih with slow kinetics
      similar to those described for the homomeric HCN2 channels, and we show that the
      Ih of the nRT contributes to the excitability of the nRT neurons in normal
      conditions.

PMID- 16617178
TI  - Nitric oxide potentiates cAMP-gated cation current in feeding neurons of
      Pleurobranchaea californica independent of cAMP and cGMP signaling pathways.
AB  - Critical roles for nitric oxide (NO) in regulating cell and tissue physiology are
      broadly appreciated, but aspects remain to be explored. In the mollusk
      Pleurobranchaea, NO synthase activity is high in CNS ganglia containing motor
      networks for feeding and locomotion, where a cAMP-gated cation current
      (I(Na,cAMP)) is also prominent in many neurons. We examined effects of NO on
      I(Na,cAMP) using voltage-clamp methods developed to analyze cAMP signaling in the
      live neuron, focusing on the identified metacerebral giant neuron of the feeding
      network. NO donors enhanced the I(Na,cAMP) response to injected cAMP by an
      averaged 85%. In dose-response measures, NO increased the current stimulated by
      cAMP injection without altering either apparent cAMP binding affinity or
      cooperativity of current activation. NO did not detectably alter levels of native
      cAMP or synthesis or degradation rates as observable in both current saturation
      and decay rate of I(Na,cAMP) responses to cAMP injection. NO actions were not
      exerted by cGMP signaling, as they were not mimicked by cGMP analogue nor blocked
      by inhibitors of guanylate cyclase and protein kinase G. NO potentiation of
      I(Na,cAMP) was broadly distributed among many other neurons of the feeding motor
      network in the buccal ganglion. However, NO did not affect a second type of
      I(Na,cAMP) found in locomotor neurons of the pedal ganglia. These results suggest
      that NO acts through a novel mechanism to regulate the gain of cAMP-dependent
      neuromodulatory pathways that activate I(Na,cAMP) and may thereby affect the set
      points of feeding network excitability and reactivity to exogenous input.

PMID- 16617179
TI  - TGF-beta1-induced long-term changes in neuronal excitability in aplysia sensory
      neurons depend on MAPK.
AB  - Transforming growth factor beta-1 (TGF-beta1) plays important roles in the early
      development of the nervous system and has been implicated in neuronal plasticity
      in adult organisms. It induces long-term increases in sensory neuron excitability
      in Aplysia as well as a long-term enhancement of synaptic efficacy at
      sensorimotor synapses. In addition, TGF-beta1 acutely regulates synapsin
      phosphorylation and reduces synaptic depression induced by low-frequency stimuli.
      Because of the critical role of MAPK in other forms of long-term plasticity in
      Aplysia, we examined the role of MAPK in TGF-beta1-induced long-term changes in
      neuronal excitability. Prolonged (6 h) exposure to TGF-beta1 induced long-term
      increases in excitability. We confirmed this finding and now report that exposure
      to TGF-beta1 was sufficient to activate MAPK and increase nuclear levels of
      active MAPK. Moreover, TGF-beta1 enhanced phosphorylation of the Aplysia
      transcriptional activator cAMP response element binding protein (CREB)1, a
      homologue to vertebrate CREB. Both the TGF-beta1-induced long-term changes in
      neuronal excitability and the phosphorylation of CREB1 were blocked in the
      presence of an inhibitor of the MAPK cascade, confirming a role for MAPK in long
      term modulation of sensory neuron function.

PMID- 16617180
TI  - A plant locus essential for phylloquinone (vitamin K1) biosynthesis originated
      from a fusion of four eubacterial genes.
AB  - Phylloquinone is a compound present in all photosynthetic plants serving as
      cofactor for Photosystem I-mediated electron transport. Newly identified seedling
      lethal Arabidopsis thaliana mutants impaired in the biosynthesis of phylloquinone
      possess reduced Photosystem I activity. The affected gene, called PHYLLO,
      consists of a fusion of four previously individual eubacterial genes, menF, menD,
      menC, and menH, required for the biosynthesis of phylloquinone in photosynthetic
      cyanobacteria and the respiratory menaquinone in eubacteria. The fact that
      homologous men genes reside as polycistronic units in eubacterial chromosomes and
      in plastomes of red algae strongly suggests that PHYLLO derived from a plastid
      operon during endosymbiosis. The principle architecture of the fused PHYLLO locus
      is conserved in the nuclear genomes of plants, green algae, and the diatom alga
      Thalassiosira pseudonana. The latter arose from secondary endosymbiosis of a red
      algae and a eukaryotic host indicating selective driving forces for maintenance
      and/or independent generation of the composite gene cluster within the nuclear
      genomes. Besides, individual menF genes, encoding active isochorismate synthases
      (ICS), have been established followed by splitting of the essential 3' region of
      the menF module of PHYLLO only in genomes of higher plants. This resulted in
      inactivation of the ICS activity encoded by PHYLLO and enabled a metabolic branch
      from the phylloquinone biosynthetic route to independently regulate the synthesis
      of salicylic acid required for plant defense. Therefore, gene fusion,
      duplication, and fission events adapted a eubacterial multienzymatic system to
      the metabolic requirements of plants.

PMID- 16617181
TI  - Structural role for Tyr-104 in Escherichia coli isopentenyl-diphosphate
      isomerase: site-directed mutagenesis, enzymology, and protein crystallography.
AB  - Isopentenyl-diphosphate (IPP):dimethylallyl diphosphate isomerase is a key enzyme
      in the biosynthesis of isoprenoids. The mechanism of the isomerization reaction
      involves protonation of the unactivated carbon-carbon double bond in the
      substrate, but identity of the acidic moiety providing the proton is still not
      clear. Multiple sequence alignments and geometrical features observed in crystal
      structures of complexes with IPP isomerase suggest that Tyr-104 could play an
      important role during catalysis. A series of mutants was constructed by directed
      mutagenesis and characterized by enzymology. Crystallographic and thermal
      denaturation data for Y104A and Y104F mutants were obtained. Those data
      demonstrate the importance of residue Tyr-104 for proper folding of Escherichia
      coli type I IPP isomerase.

PMID- 16617182
TI  - Painful Hashimoto's thyroiditis.

PMID- 16617183
TI  - Treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma.

PMID- 16617184
TI  - Successful colectomy for the treatment of repetitive bleeding from colonic
      angiodysplasia in a patient with Heyde syndrome.
AB  - A 64-year-old man with repetitive gastrointestinal bleeding was admitted to our
      hospital. Colonic artery angiography revealed angiodysplasia as the bleeding
      site, and echocardiography showed aortic valve stenosis. A decrease in the high
      molecular weight von Willebrand factor multimers, which are known to play an
      important role in hemostasis, was observed, and Heyde syndrome was diagnosed. We
      selected colectomy instead of aortic valve replacement because the patient had
      undergone two open heart surgeries. Following colectomy, the patient showed a
      good clinical course without recurrent gastrointestinal bleeding. Colectomy might
      serve as a therapeutic option for Heyde syndrome after the precise site of
      angiodysplasia is detected by angiography.

PMID- 16617186
TI  - Sarcoidosis with acute recurrent polyarthritis and hypercalcemia.
AB  - A 45-year-old woman had bleary eyes and recurrent episodes of fever and arthritis
      in the knees and ankles. The patient had anterior uveitis, negative findings of
      the tuberculin test, and an increased serum lysozyme level, but bilateral hilar
      lymphadenopathy (BHL) was absent. During the course of her disease, the serum
      calcium and angiotensin-converting enzyme levels gradually increased to above the
      normal level, and the patient was clinically diagnosed as having sarcoidosis. The
      clinical features of arthritis were typical of those of Lofgrens syndrome
      although BHL and erythema nodosum were absent. The patient was successfully
      treated with 15 mg/day of prednisolone.

PMID- 16617185
TI  - Pulmonary sarcoidosis with usual interstitial pneumonia distributed predominantly
      in the lower lung fields.
AB  - Nodular and reticular opacities were detected in both lower lung fields of a 75
      year-old man in 2000. Bronchoscopy revealed pulmonary sarcoidosis. In 2002,
      nodular and reticular opacities were shown in the right upper lobe, and video
      assisted thoracoscopic surgery was performed. The histological findings revealed
      usual interstitial pneumonia (UIP)-like lesions, whereas non-caseous granulomas
      were not detected. In the present case of pulmonary sarcoidosis, nodular and
      reticular opacities were predominantly distributed in both lower lung fields, and
      the histological findings obtained by video-assisted thoracoscopic surgery showed
      UIP-like lesions. These findings may enlighten the assist in understanding of the
      process of development of pulmonary sarcoidosis.

PMID- 16617187
TI  - Pulmonary cryptococcosis within a pulmonary carcinoma-review of reported cases.
AB  - An asymptomatic 71-year-old man was admitted for evaluation of a pulmonary tumor.
      Chest computed tomography revealed a cavitary tumor in the apical segment of the
      right lung. Histopathological examination of the resected lung revealed pulmonary
      cryptococcosis within a papillary adenocarcinoma. Macroscopic and
      histopathological findings speculated that papillary adenocarcinoma preceded
      pulmonary cryptococcosis.

PMID- 16617188
TI  - Vaccine-associated paralytic poliomyelitis caused by contact infection.
AB  - We encountered an adult patient with acute anterior poliomyelitis (AAP), whose
      monoparesis developed 28 days after his son's immunization with oral poliovirus
      vaccine (OPV). Neurological and electrophysiological examinations suggested that
      his muscular wasting of the left lower limb was due to a lower motor neuron
      disorder, and magnetic resonance imaging revealed the responsible lesion in the
      left anterior horn at the thoracolumbar junction. His stool was found to include
      poliovirus type 3, mainly originating from Sabin 3 by neutrization antibody and
      PCR-restriction fragment length polymorphism method. This indicated that the AAP
      resulted from contact with his son. This patient raises the question about OPV in
      polio-free countries.

PMID- 16617189
TI  - Gender-related differences in target organ damage in untreated patients with
      essential hypertension.
AB  - We examined the gender-related differences in target organ damage in 220
      untreated patients with essential hypertension (106 men and 114 women). As the
      indices of target organ damage, we examined the left ventricular mass index and
      the intima-media thickness in the carotid and femoral arteries obtained from
      echocardiography. In a multiple regression model, there was a significant
      positive correlation between the intima-media thickness and age in both groups.
      In men, there was a significant positive correlation between the left ventricular
      mass index and age, as well as the diastolic blood pressure, and body mass index.
      In women, there was a significant positive correlation between the left
      ventricular mass index and age, as well as plasma renin activity and smoking. In
      conclusion, there are gender-related differences in the contributing factors,
      which relate to left ventricular hypertrophy in patients with essential
      hypertension.

PMID- 16617190
TI  - Four cases of Graves' disease which developed after painful Hashimoto's
      thyroiditis.
AB  - We report four cases of Graves' disease that developed after painful Hashimoto's
      thyroiditis. All were middle-aged women, who had high titers of anti-thyroid
      antibodies and thyrotoxicosis at the onset of painful Hashimoto's thyroiditis.
      After 2 to 7 years, they developed Graves' disease with positive antibody against
      the thyrotropin receptor. Their clinical courses of Graves' disease went
      favorably due to the treatment with antithyroid drug or radioactive iodine
      therapy. Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's
      thyroiditis and is one form of destructive thyroiditis. Thyroid damage due to
      painful Hashimoto's thyroiditis may be associated with the development of Graves'
      disease.

PMID- 16617191
TI  - New non-invasive automatic cough counting program based on 6 types of classified
      cough sounds.
AB  - Cough consisting of an initial deep inspiration, glottal closure, and an
      explosive expiration accompanied by a sound is one of the most common symptoms of
      respiratory disease. Despite its clinical importance, standard methods for
      objective cough analysis have yet to be established. OBJECT: We investigated the
      characteristics of cough sounds acoustically, designed a program to discriminate
      cough sounds from other sounds, and finally developed a new objective method of
      non-invasive cough counting. In addition, we evaluated the clinical efficacy of
      that program. SUBJECTS AND METHODS: We recorded cough sounds using a memory stick
      IC recorder in free-field from 2 patients and analyzed the intensity of 534
      recorded coughs acoustically according to time domain. First we squared the sound
      waveform of recorded cough sounds, which was then smoothed out over a 20 ms
      window. The 5 parameters and some definitions to discriminate the cough sounds
      from other noise were identified and the cough sounds were classified into 6
      groups. Next, we applied this method to develop a new automatic cough count
      program. Finally, to evaluate the accuracy and clinical usefulness of this
      program, we counted cough sounds collected from another 10 patients using our
      program and conventional manual counting. And the sensitivity, specificity and
      discriminative rate of the program were analyzed. RESULTS: This program
      successfully discriminated recorded cough sounds out of 1902 sound events
      collected from 10 patients at a rate of 93.1%. The sensitivity was 90.2% and the
      specificity was 96.5%. CONCLUSION: Our new cough counting program can be
      sufficiently useful for clinical studies.

PMID- 16617192
TI  - Exercise training for the improvement of exercise performance of patients with
      pulmonary tuberculosis sequelae.
AB  - OBJECTIVE: To examine whether exercise training using nontreadmill walking is
      effective for the improvement of exercise performance of patients with pulmonary
      tuberculosis sequelae (PTS) characterized by restrictive ventilatory defect.
      PATIENTS AND METHODS: Fourteen patients with stable PTS hospitalized for
      assessment of exertional dyspnea in Fukujuji Hospital from April 1997 to March
      1999 were enrolled in this observational study. All patients underwent baseline
      pulmonary function tests, arterial blood-gases analysis and exercise tests for
      initial assessment. Four patients were excluded because of hypoxemia during the
      initial treadmill test. The remaining 10 patients who stopped exercising because
      of symptom limitations became candidates for the exercise training. The patients
      were instructed to perform daily walking exercise training in a hallway in the
      hospital for 2 weeks. The training was started at their maximum walking speeds
      during the treadmill test, and walking speed was gradually increased as the
      patients gained confidence. After finishing the exercise training, the patients
      performed pulmonary function tests, arterial blood-gases analysis was done, and
      exercise tests were conducted in identical fashion to the baseline protocol.
      RESULTS: There were no significant changes in pulmonary function tests and
      arterial blood-gases analysis after the exercise training. Exercise tolerance
      improved with a significant increase in peak oxygen uptake (from 13.6+/-2.8 to
      14.8+/-2.8 ml/kg/min, p<0.01) and distance covered in a 6-minute walk (from 399+/
      62 to 467+/-65 m, p<0.01) after the exercise training. CONCLUSION: The exercise
      training we conducted is shown to be a safe and effective modality for the
      improvement of exercise performance of patients with PTS.

PMID- 16617193
TI  - Outcome of radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma
      refractory to Helicobacter pylori eradication therapy.
AB  - BACKGROUNDS AND AIMS: Most low-grade gastric mucosa-associated lymphoid tissue
      (MALT) lymphomas respond to eradication of H. pylori, however, some are
      refractory. The effectiveness of radiotherapy for MALT lymphoma refractory to H.
      pylori eradication has been demonstrated. However, the long-term outcome and
      associated late radiation morbidity of radiotherapy for gastric MALT lymphoma are
      unclear. We evaluated the efficacy of radiotherapy and the radiation-associated
      adverse effects for gastric MALT lymphoma refractory to H. pylori eradication
      therapy. METHODS: Eighteen patients with H. pylori-positive gastric MALT lymphoma
      received H. pylori eradication therapy, of which three patients refractory to
      eradication of H. pylori were subsequently treated with irradiation (median 39
      Gy, range 36-40 Gy). Efficacy of radiotherapy and associated radiation morbidity
      were evaluated. Adverse events were evaluated according to RTOG and NCI-CTC
      criteria. RESULTS: Radiation was well tolerated. All three patients treated with
      radiotherapy achieved complete remission, which was sustained for a median follow
      up period of 42.0 months (range, 24-72 months). As acute radiation side effects,
      all patients experienced mild nausea (Grade 1 by RTOG and 1 point [1 category] in
      NCI-CTC). One patient had Grade 1 appetite loss. There were no severe late
      adverse events. One patient had left kidney atrophy of approximately 10%, but
      none had renal dysfunction. CONCLUSIONS: Radiotherapy for patients with gastric
      MALT lymphoma refractory to H pylori eradication was effective without any
      critical acute or late adverse events.

PMID- 16617194
TI  - Oral health status and health-related quality of life: a systematic review.
AB  - This study was conducted in order to identify the literature on oral health
      status and health-related QOL, review the findings systematically, and assess the
      association between them. We performed a literature search of reports published
      between January 1973 and June 2004, using five databases including MEDLINE. Only
      studies that used validated generic health-related QOL instruments were selected.
      The reviewers evaluated selected articles independently and resolved
      disagreements by consensus. A total of 1,726 articles were retrieved and seven
      were selected for the review; five observational studies and two intervention
      studies. Four studies showed significant associations between oral health status
      and health-related QOL. Temporomandibular disorders were highly associated with
      reduced health-related QOL. Poor oral status linked to both craniomandibular and
      cervical spinal pain was associated with increased impairment of health-related
      QOL. Dissatisfaction with the teeth and mouth, and a sensation of dry mouth
      contributed to reduce health-related QOL. Providing edentulous patients with
      implant-supported full dentures contributed to improve health-related QOL.
      Assessment of health-related QOL in relation to oral health with validated
      instruments remains insufficient. The present findings suggest that oral health
      status could affect health-related QOL in some settings; however, further
      evidence is needed to support this interpretation.

PMID- 16617195
TI  - Localization of FGF-6 and FGFR-4 during prenatal and early postnatal development
      of the mouse sublingual gland.
AB  - A number of fibroblast growth factors (FGFs) are involved in regulatory
      mechanisms of the salivary gland development. However, the role of FGF-6 unique
      in myogenic cells has not been elucidated in the developing sublingual gland. In
      the present study, temporo-spatial expression of FGF-6 and its receptor (FGFR)-4,
      in conjunction with some related histo-chemical properties, were investigated in
      the sublingual gland of the prenatal and early postnatal mice. The earliest
      expression of both FGF-6 and FGFR-4 was detected in immature acinar cells at
      gestational day 17 (GD17). The staining intensity increased gradually and some
      acinar cells showed a distinct staining at postnatal day 0 (PD0). The
      immunopositive cells had a relatively round profile and were assumed to be acinar
      cells. The positive staining decreased thereafter and disappeared completely by
      PD11. To confirm the identity of cells positive for FGF-6, double immunolabeling
      with anti-alphasmooth muscle actin (alphaSMA) and anti-FGF-6 antibodies was
      performed. The positive staining of alphaSMA, a marker of myoepithelial cells,
      was detected in the flattened cells surrounding the acini but not in the cells
      positive for FGF-6. The staining properties of secretory granules in acinar cells
      were also examined with periodic acid-Shiff (PAS) and alcian blue (AB). PAS
      positive granules abundant in the late gestational stages (GD17 to PD0) began to
      be replaced with AB-positive mucous granules at early neonatal days (PD0-3), when
      the FGF-6/FGFR-4 expression was the strongest. These findings suggest that FGF
      6/FGFR-4 might be involved in the changes of secretory granule content of acinar
      cells in the sublingual gland during the late gestational and early neonatal
      stages.

PMID- 16617196
TI  - Removal resistance of glass-fiber and metallic cast posts with different lengths.
AB  - This study evaluated the strength required to remove glass-fiber and metallic
      cast posts with different lengths. Sixty endodontically treated canines were
      included and their roots were embedded in acrylic resin after discarding the
      crowns. Samples were randomly assigned to 3 groups according to the post length
      (n = 20): I- 6 mm, II - 8 mm and III- 10 mm. Each group was divided into 2
      subgroups based on the post material (n = 10): A- glass fiber or B- metallic
      cast. Post-space was prepared with Fibrekor Post Kit attached to a
      parallelometer. In subgroup A, prefabricated glass fiber posts from Fibrekor Post
      Kit were utilized. In metallic post group (subgroup B), an impression of post
      space was obtained, followed by casting. All posts were luted with Panavia F
      cement. A universal testing machine determined the force required to dislodge
      each post. ANOVA analysis indicated significant differences (P < 0.01) among post
      length. Tukey test showed that posts with 10 mm-length showed higher resistance
      on removal than posts with 6 mm-length. Posts with 8 mm-length did not exhibit
      difference when compared to 6 and 10 mm posts. No significant differences (P >
      0.05) were observed between the tested post materials. It was concluded that the
      type of post did not influence the removal resistance and that posts with 10 mm
      length required greater force to be dislodged.

PMID- 16617197
TI  - Influence of light intensity on dentin bond strength of self-etch systems.
AB  - The purpose of this study was to investigate the influence of light intensity on
      dentin bond strengths of four self-etch adhesive systems. The light intensities
      used to polymerize specimens were controlled at levels of 150, 300, 600, and 900
      mW/cm2. The two-step self-etch adhesive systems Imperva Fluoro Bond and Mac Bond
      II, and the one-step self-etch systems Fluoro Bond Shake-One and One-Up Bond F
      Plus were used with their corresponding light-cured resins. Labial surfaces of
      lower bovine incisors were ground with #600 grit SiC paper to expose the dentin.
      The dentin surfaces were treated according to each manufacturer's instructions
      and bonded with resin composites. A shear bond strength test was performed and
      the data were analyzed by one-way ANOVA followed by Newman-Keuls multiple
      comparison at a level of 0.05. Statistical analysis of the data indicated that
      light intensity affected the dentin bond strengths of the adhesive systems
      tested. Significantly lower bond strengths were obtained by exposure to 150
      mW/cm2, and there were no differences between the bond strengths obtained at 600
      and 900 mW/cm2 for all the adhesive systems used. Further research will be
      required to clarify the irradiance-dependent properties of light-cured resin
      adhesive systems.

PMID- 16617198
TI  - Comparison of image performance between cone-beam computed tomography for dental
      use and four-row multidetector helical CT.
AB  - The authors evaluated the imaging performance of cone-beam computed tomography
      (CBCT) for dental use using 3DX multi-image micro-CT (Morita Co., Kyoto, Japan)
      and four-row multi-detector helical computed tomography (MDCT) using an Asteion
      (Toshiba, Tokyo, Japan). A dried right maxillary bone was cut into eight slices 2
      mm thick toward the zygomatico-palate and used as a phantom. Images of the
      phantom were then taken using 3DX and MDCT. The images of two bone slices were
      evaluated by five dentists for image quality and reproducibility of cancellous
      bone, as well as enamel, dentin, pulp cavity, periodontal ligament space, lamina
      dura and the overall image. Using the MDCT images as the standard, the 3DX images
      were evaluated with a subjective 5-level scale: 3 for an image equal to the MDCT
      image, 4 or greater for better, and 2 or lower for worse. The scores for all
      parameters exceeded 4 points. Maximum mean score was 4.8 for the lamina dura.
      Statistically significant differences were found for all items (P < 0.01). Our
      subjective evaluation of imaging performance clarified that 3DX was superior to
      MDCT. The results of this study suggest that 3DX is useful for imaging in the
      dental field.

PMID- 16617199
TI  - Bifid mandibular condyle: a case report.
AB  - The bifid mandibular condyle is a rare anomaly. A variety of causes are
      implicated with its development such as developmental origin and trauma. Because
      of the lack of epidemiological data, there is little information about the real
      incidence of this malformation. The purpose of this paper is to report a case of
      bifid mandibular condyle in a 20-year-old woman who referred to a private
      radiological clinic for routine dental examination. A panoramic radiography
      incidentally revealed a discrete modification of the left mandibular condyle.
      Magnetic resonance imaging (MRI) was taken and confirmed the diagnostic proposed.

PMID- 16617200
TI  - Endodontic treatment of a supernumerary tooth fused to a mandibular second molar:
      a case report.
AB  - Since abnormal tooth morphology can predispose to caries and periodontal disease,
      careful management of fused teeth is essential. In this paper we report a rare
      case of a fused molar and supernumerary tooth and describe its management. Caries
      was removed from the tooth complex under local anesthesia. The pulp chamber of
      the supernumerary tooth was exposed without involvement of second molar pulp
      chamber. The root canal of the supernumerary tooth was prepared using the step
      back technique and copious irrigation with 2.6% sodium hypochlorite. Obturation
      using the lateral condensation technique with gutta-percha and AH26 sealer was
      subsequently performed and final restoration was accomplished with composite
      resin. Nine months after the treatment, no clinical or radiographic concern is
      apparent, and the second molar tooth has remained vital.

PMID- 16617201
TI  - Characterization of oral pemphigus vulgaris in Thai patients.
AB  - Pemphigus vulgaris (PV) is a serious mucocutaneous disease that be fatal if left
      untreated. The oral mucosa is often the first site to be affected by the disease.
      It is thus important that the dentist is able to recognize oral manifestations of
      PV and refer appropriately. Although oral PV is a well-characterized condition,
      the disease characteristics of patients in Thailand have not been previously
      reported. Here, we describe patient and lesion characteristics of 18 cases of
      oral PV. For these 18 cases, the mean age was 38 years, and the male:female ratio
      was 1:2. The most commonly affected sites were the gingiva and buccal mucosa, and
      the duration of disease was approximately one year. Medications previously used
      included corticosteroids and interferon, and nine patients reported systemic
      disease. Histopathologic examination with/without direct immunofluorescence was
      the method of diagnosis in all cases.

PMID- 16617202
TI  - Blood volume and haemoglobin oxygen content changes in human bone marrow during
      orthostatic stress.
AB  - The interest in, and the need for effective measures to be used in screening,
      diagnosis, and the follow-up of skeletal pathologies is growing markedly. This
      paper proposes a completely new and non-invasive technique allowing the study of
      the human tibia bone marrow (BM) haemodynamics with a time resolution of 1 s. The
      technique, based on near infrared spectroscopy, is sensitive enough to allow the
      detection of BM blood volume and/or oxygen saturation changes during orthostatic
      variations imposed by a tilt bed. An increase in the slope of the bed of 15
      degrees is sufficient to detect this phenomenon. The ability to study the
      possible presence of a neural control of BM haemodynamics is also discussed. No
      other existing technique currently allows one to obtain the proposed results and
      this approach might open up a new field of study related to human BM physiology.

PMID- 16617203
TI  - Physiological and subjective responses to low relative humidity.
AB  - In order to investigate the influence of low relative humidity, we measured
      saccharin clearance time (SCT), frequency of blinking, heart rate (HR), blood
      pressure, hydration state of skin, transepidermal water loss (TEWL), recovery
      sebum level and skin temperature as physiological responses. We asked subjects to
      judge thermal, dryness and comfort sensations as subjective responses using a
      rating scale. Sixteen non-smoking healthy male students were selected. The pre
      room conditions were maintained at an air temperature (Ta) of 25 degrees C and a
      relative humidity (RH) of 50%. The test room conditions were adjusted to provide
      a Ta of 25 degrees C and RH levels of 10%, 30% and 50%.RH had no effect on the
      activity of the sebaceous gland and on cardiovascular reactions like blood
      pressure and HR. However, it was obvious that low RH affects SCT, the dryness of
      the ocular mucosa and the stratum corneum of the skin and causes a decrease in
      mean skin temperature. Under 30% RH, the eyes and skin become dry, and under 10%
      RH the nasal mucous membrane becomes dry as well as the eyes and skin, and the
      mean skin temperature decreases. These findings suggested that to avoid dryness
      of the eyes and skin, it is necessary to maintain an RH greater than 30%, and to
      avoid dryness of the nasal mucous membrane, it is necessary to maintain an RH
      greater than 10%. Subjects felt cold immediately after a change in RH while they
      had only a slight perception of dryness at the change of humidity.

PMID- 16617204
TI  - The frequency of fingerprint type in parents of children with Trisomy 21 in
      Japan.
AB  - Analysis of the frequency data of each fingerprint type (arch, ulnar loop, radial
      loop, and whorl) of the parents of children with Trisomy 21 (Fathers: 71;
      Mothers: 128) born between 1965 and 1970 obtained from the Tokyo Medical and
      Dental University Hospital was carried out. Japanese controls were taken from
      dermatoglyphics data in Japan. We conducted the Friedman test on each type of
      fingerprint between Japanese controls and parents of Trisomy 21 children. Results
      from a statistical analysis based on the above data showed significant
      differences, more arches (p < 0.0001) and fewer whorls (p < 0.05) in mothers of
      children with Trisomy 21. Among fathers of Trisomy 21 children, a significant
      difference was found in there being fewer whorls (p < 0.05) and ulnar loops (p =
      0.06). Considering the mothers' fingerprints, we suspected that females with a
      higher frequency of arches and a lower frequency of whorls had a stronger
      possibility of bearing Trisomy 21 babies. On the other hand, in fathers of
      Trisomy 21 children, we considered that there would be a possibility of
      significant differences if cases in the sample were increased.

PMID- 16617205
TI  - The influence of different target values and measurement times on the decreasing
      force curve during sustained static gripping work.
AB  - The purposes of this study were to clarify the decreasing properties of, and to
      examine useful measurement times for evaluating muscle endurance in a comparison
      among various parameters using measurement times of 1, 3 and 6 mins and target
      values of 50, 75 and 100% MVC. Fifteen males and 15 females participated in this
      study. All subjects carried out sustained isometric gripping under nine
      conditions of measurement times and target forces, (1, 3 and 6 mins vs. 50, 75
      and 100% MVC) with an interval of one or two days. The property of decreasing
      force in the initial phase (marked decreasing phase) differed among the target
      values, and the decreasing speed of the gripping force was highest for 100% MVC.
      However, the decreasing property after about 60 sec, in which the force decreased
      to about 30% MVC from the onset of grip, was similar among all target values, and
      then the gripping force reached an almost steady state phase at about 150-180
      sec. In other words, the difference of the decreasing property during the initial
      phase with different target values was considered not to influence the property
      in the later phase, in which the force decreases to about 30% MVC. When muscle
      endurance is evaluated from the phase until reaching the steady state, it may be
      possible to evaluate the same property of the decreasing phase at 6 min as the
      measurement at 3 min. The measurement for 1 min at 50% MVC was not valid as an
      evaluation time because the grip force did not decrease enough. The integrated
      area in the initial phase was considered to depend on the magnitude of the target
      value, and the integrated area for 30 sec or 60 sec at 75% MVC was larger than
      that at 100% MVC. It was inferred that higher pain at 100% MVC resulted in a
      greater decrease in the speed of the force.

PMID- 16617206
TI  - Seasonal variations of physiological characteristics and thermal sensation under
      identical thermal conditions.
AB  - Seasonal variations of human thermal characteristics were inspected in thermal
      comfort and when constantly indoors. Metabolic rate, tympanic temperature, skin
      temperature, body fat, body weight and thermal sensation were measured under
      identical thermal conditions in a chamber over the course of one year.
      Experiments were carried out for each subject in both summer and winter. Six
      subjects were measured 35 times in summer and 45 times in winter. one subject was
      measured weekly for 14 months. Measurements for analyses were taken 40-60 min
      after entrance into the chamber. Results revealed the following. 1) For all
      subjects, the metabolic rate, tympanic temperature and body fat were lower in
      summer than in winter; thigh skin temperatures were higher in summer than in
      winter. The averaged individual ratio of seasonal difference was 11.9% for
      metabolic rate, 14.9% for body fat, 1.8% for thigh temperature and 0.53% for
      tympanic temperature. Seasonal differences of about 10% in metabolic rate were
      maintained in this study. 2) Seasonal variations of the variables were examined
      for phase relationships against the outdoor temperature. 2-1) Metabolic rate,
      thermal sensation, body weight and body fat changed in reverse phase, whereas
      skin temperature was in-phase. 2-2) Skin temperature lagged by about one month in
      both summer and winter. Body fat also lagged by about one month in summer, but
      corresponded to the phase in winter. Metabolic rates were also in-phase in winter
      but led about three months in summer. Thermal sensations lagged by about three
      months in winter but were in-phase in summer. Body weight was in-phase in summer
      and winter. 2-3) Summer disorders were observed particularly in seasonal
      variations of metabolic rates, tympanic temperature, skin temperatures, and
      thermal sensation, thereby suggesting that the effect of temperature exposure was
      altered by air-conditioner use.

PMID- 16617208
TI  - Diurnal changes of ERP response to sound stimuli of varying frequency in morning
      type and evening-type subjects.
AB  - In order to study the cognitive function rhythm related to the auditory frequency
      system for people who prefer to be active in the morning and at night, we
      conducted an experiment during morning (09:00), evening (17:00) and late-night
      (01:00) periods. On the basis of a morningness/eveningness questionnaire, six
      moderately morning-type subjects (M-types) and seven evening-type subjects (E
      types) were selected. Diurnal variation of event-related potential (ERP) were
      assessed under low-frequency (250/500 Hz) and high-frequency (1000/2000 Hz)
      condition using an oddball task. M-types were tested during the morning (09:00)
      and evening (17:00) periods, and E-types were tested during the evening (17:00)
      and midnight (01:00) periods. Subjects were asked to press a button when the
      target stimulus was detected. We found that the P300 amplitude at 09:00 was
      significantly greater than that at 17:00 for M-types, was significantly greater
      at 17:00 than that at 01:00 for E-types. A significant difference of P300 latency
      and P300 amplitude was observed at 17:00 between M-types and E-types. The P300
      amplitude obtained after a low-frequency stimulus was significantly greater than
      that after a high-frequency stimulus at 09:00 for M-types, and at 01:00 for E
      types. These results revealed that stimulus frequency had effects on the diurnal
      changes of human cognitive function, and circadian typology had a direct effect
      on the diurnal change of human cognitive function. This study has extended the
      previous findings of auditory P300 studies on diurnal variations in terms of
      circadian typology and stimulus parameter.

PMID- 16617207
TI  - Overweight in urban schoolchildren assessed by body mass index and body fat mass
      in Dalian, China.
AB  - In order to assess overweight in urban schoolchildren (298 boys and 298 girls)
      aged 9-16 years in Dalian, China, their body height, weight, skinfolds at
      triceps, biceps, subscapular and suprailiac, and body circumferences of mid-upper
      arm, waist and hip were measured. The results showed that the prevalence of
      overweight, based on the United States Centers for Disease Control 2000 reference
      values using body mass index (BMI), was 22.9% in boys and 10.4% in girls, which
      was higher than that of indicated in Chinese national surveys of recent decades.
      More boys were overweight than girls due to excessive increase in body fat,
      although the prevalence of overweight in girls prevalence increased from 13
      years. Discussion here focuses on the effects of behavioral patterns on
      overweight in Dalian schoolchildren, paying attention to gender difference.

PMID- 16617209
TI  - Physiological anthropology design: a comparative study between Germany and Japan.
AB  - With the recent globalization of industrial products, there is doubt as to
      whether the methodology of Physiological Anthropology has also been standardized.
      The purpose of this study is to assess signs of standardization through a
      comparative analysis of Physiological Anthropology design in Germany and Japan.
      This survey investigates its characteristics through four factors: comfort,
      usability, sensation and aesthetics. Both nations regard the first three
      indicators as important. The difference in assessment is, however, considerable.
      While German physiological anthropologists use subjective evaluation by means of
      questionnaires, somatometry and biomechanical analysis, their Japanese
      counterparts apply physiological measurements of the higher nervous system and
      the autonomic nervous system. Polymorphism and improving functional potentiality
      have recently gained increasing respect in Japan. Notions of aesthetics are not
      consciously analyzed in both countries. If the sense of beauty of product design
      relates to a physical and mental response, developing a systematic analysis on
      this factor would be a useful task for Physiological Anthropology.

PMID- 16617210
TI  - Energy expenditure in maximal jumps on sand.
AB  - The purpose of this study was to comparatively investigate the energy expenditure
      of jumping on sand and on a firm surface. Eight male university volleyball
      players were recruited in this study and performed 3 sets of 10 repetitive jumps
      on sand (the S condition), and also on a force platform (the F condition). The
      subjects jumped every two seconds during a set, and the interval between sets was
      20 seconds. The subjects performed each jump on sand with maximal exertion while
      in the F condition they jumped as high as they did on sand. The oxygen
      requirement for jumping was defined as the total oxygen uptake consecutively
      measured between the first set of jumps and the point that oxygen uptake recovers
      to the resting value, and the energy expenditure was calculated. The jump height
      in the S condition was equivalent to 64.0 +/- 4.4% of the height in the maximal
      jump on the firm surface. The oxygen requirement was 7.39 +/- 0.33 liters in S
      condition and 6.24 +/- 0.69 liters in the F condition, and the energy expenditure
      was 37.0 +/- 1.64 kcal and 31.2 +/- 3.46 kcal respectively. The differences in
      the two counter values were both statistically significant (p < 0.01). The energy
      expenditure of jumping in the S condition was equivalent to 119.4 +/- 10.1% of
      the one in the F condition, which ratio was less than in walking and close to in
      running.

PMID- 16617211
TI  - Physiological anthropology: past and future.
AB  - Environmental studies in adaptive human biology by North American anthropologists
      have a history of strong investigative research. From both laboratory and field
      work, we have gained major insights into human response to physical and social
      challenges. While these results were considered by most professionals to belong
      within evolutionary biology, in fact the intellectual structure sprang almost
      entirely from physiological equilibrium models. Consequently, physiological
      process itself was the focus. Further, most of the physiological patterns were
      not linked directly to important outcomes such as work output, reproductive
      success or survival. About 1975, American physiological anthropologists, led by
      Paul Baker, turned to studies of health, change and stress response. These
      studies were strong, but were still neither genetic nor evolutionary in
      intellectual structure. Evolutionary human biology was taken over by a new body
      of theory now called "behavior ecology", positing that selfish genes control
      human behavior to promote their own reproduction. This was paralleled by strong
      use of evolutionary theory in some areas of molecular biology. However, although
      physiological anthropologists have not focused on evolution, we have been
      developing powerful causal models that incorporate elements of physiology,
      morphology, physical environment and cultural behavior. In these "proximate"
      biocultural models, it is of little importance whether outcomes such as work or
      energy management are genetically based. Our future offers two major challenges.
      First, we must confirm causal links between specific physiological patterns and
      outcomes of practical importance to individuals and societies. Second, if we are
      to take our place in evolutionary biology, the one overarching theory of life on
      earth, we must understand the heritability of physiological traits, and determine
      whether they play a role in survival and reproduction.

PMID- 16617213
TI  - Menstrual cycle characteristics and predictability of ovulation of Bhutia women
      in Sikkim, India.
AB  - Although a woman's menstrual history can have significant implications for health
      outcomes, few studies have examined menstrual cycle variability in non-western,
      non-clinically based populations. This study presents menstrual cycle
      characteristics from Bhutia women living in Gangtok, Sikkim, India. The Bhutia
      are one of two indigenous populations residing in this small, northeastern state
      of India. A total of 1067 cycles were recorded by 200 Bhutia women over the
      course of 12 months. Mean cycle length in this population was similar to reported
      mean cycle lengths for populations in the U.S (30 days vs. 28 days). Menstrual
      cycles in this sample were highly variable with most women experiencing more than
      one short or long menstrual cycle. The frequency of irregular menstrual cycles
      experienced by individuals also varied significantly by season. A body mass index
      (BMI) above or below the WHO defined normal range was associated with higher
      rates of irregular cycles. Leutenizing hormone (LH) and follicle stimulating
      hormone (FSH) levels were also determined from urine samples collected just
      before mid-cycle, based on median cycle lengths. Although menstrual cycles in
      this sample were highly variable, median cycle length was still useful in
      predicting timing of the pre-ovulatory hormone surges of LH and FSH. Frequency of
      irregular cycles did impact the successful capture of the LH and FSH peak values.

PMID- 16617212
TI  - The emergence of obesity among indigenous Siberians.
AB  - Once considered a disease of affluence and confined to industrialized nations,
      obesity is currently emerging as a major health concern in nearly every country
      in the world. Available data suggest that the prevalence rate of obesity has
      reached unprecedented levels in most developing countries, and is increasing at a
      rate that far outpaces that of developed nations. This increase in obesity has
      also been documented among North American circumpolar populations and is
      associated with lifestyle changes related to economic development. While obesity
      has not been well studied among indigenous Siberians, recent anthropological
      studies indicate that obesity and its associated comorbidities are important
      health problems.The present study examines recent adult body composition data
      from four indigenous Siberian populations (Evenki, Ket, Buriat, and Yakut) with
      two main objectives: 1) to determine the prevalence of overweight and obesity
      among these groups, and 2) to assess the influence of lifestyle and socioeconomic
      factors on the development of excess body fat. The results of this study indicate
      that obesity has emerged as an important health issue among indigenous Siberians,
      and especially for women, whose obesity rates are considerably higher than those
      of men (12% vs. 7%). The present study investigated the association between
      lifestyle and body composition among the Yakut, and documented substantial sex
      differences in lifestyle correlates of obesity. Yakut men with higher incomes and
      who owned more luxury consumer goods were more likely to have excess body fat
      while, among Yakut women, affluence was not strongly associated with overweight
      and obesity.

PMID- 16617214
TI  - Low salivary cortisol and elevated depressive affect among rural men in Botswana:
      reliability and validity of laboratory results.
AB  - Most research on hypothalamic-pituitary-adrenal axis function under aversive
      conditions has focused on relatively increased acute episodic, or chronic
      secretions as an operationalization of "stress." Severe or recurrent stress,
      perhaps in interaction with individual characteristics, results in chronically
      decreased HPA function among some persons suffering from posttraumatic stress
      disorder. Little evidence exists to assess the population distribution of chronic
      low cortisol in different free-ranging human populations, as a manifestation of
      past trauma or stress. This study reports findings of chronically depressed
      ambulatory salivary cortisol among rural-dwelling Batswana men (n=30) compared
      with men living in Gaborone (n=34), the capital of Botswana, based on repeated
      ambulatory sampling. Out of 914 saliva samples analyzed by radioimmunoassay, 268
      (29.3%) samples (41 urban, 227 rural) were below the minimum detectable dose
      (<MDD of 0.034 ug/dL) of the assay. Low values were distributed across comparable
      times of day as were =MDD samples. There was significant clustering of low
      cortisol within individuals; percentage of intra-individual repeats that were
      <MDD ranged from zero to 94.1% for rural participants (median=59.8%; mean=54.8%;
      SD=27.8%), and from zero to 40% for urban (median=0%; mean=8%; SD=11.9%). There
      was no association between number of repeats and proportion <MDD (P[F=
      0.47]=0.639; beta(1)=-0.0045+/-0.0019). Examination of laboratory quality control
      suggests that this pattern is not a result of measurement error, or poor sample
      preservation, but instead reflects a difference from residing in a remote rural
      versus a central urban community.

PMID- 16617215
TI  - Effects of pollution on human growth and development: an introduction.
AB  - Pollution is a worldwide problem and its potential to influence the physiology of
      human populations is great. Studies of human growth and development in relation
      to pollution have increased in number and quality since the mid-twentieth
      century. Many studies have found that some pollutants have detrimental effects on
      human growth, particularly prenatal growth. The heavy metal, lead, is commonly
      found in human populations and is related to smaller size at birth and studies
      have reported decrements that range up to about 200 grams. Noise stress from
      transportation sources also is related to reduced prenatal growth with somewhat
      smaller decrements reported. Studies of humans exposed to polychlorinated
      biphenyls, one of the persistent organic pollutants, have reduced size at birth,
      advanced sexual maturation and altered hormone levels related to thyroid
      regulation. Thus different pollutants exert effects through different
      physiological pathways. However, some studies have not observed these effects,
      which indicates that the situation is complex and requires further study with
      better study designs. Determining the effects of pollutants on human physiology
      and growth is difficult as it requires fairly large numbers of subjects who are
      not purposely exposed but for whom exposure can be measured. These effects of
      pollutants and the mechanisms of effect require further study to understand and,
      it is hoped, to blunt or block any detrimental effects on human health and well
      being.

PMID- 16617216
TI  - Aging, disability, and frailty: implications for universal design.
AB  - Throughout the world all populations are seeing burgeoning numbers of "elders",
      defined as persons aged 65 year and older. In many countries, including Japan,
      the United States, Norway, Sweden and the United Kingdom, those aged over 65 are
      at or approaching 15% of the population. As their numbers have increased, so have
      their health care expenses, leading to extensive research on the health, well
      being, and life expectancy of these increasingly older elders. Today this group
      is further sub-divided: the young-old ages 65-74, the old-old ages 75-84, and the
      oldest-old ages 85+, for both health care and research purposes. However broad
      variation still characterizes even these groupings. Rates of frailty and
      disability increase with increasing age among these elders. For example,
      inabilities to complete at least one activity of daily living increased from
      about 5-7% at ages 65-69 years to about 28-36% at ages 85+ in 1987. Death rates
      continue to decline at all ages past 50 years and rates of disability seem to be
      doing the same. For the foreseeable future, we may expect increasing numbers of
      older, frail elders than in previous decades. Thus, people are not only living
      longer, they generally are healthier at advanced ages than were previous cohorts,
      thus "old age" disabilities of the 20th century will be put off to even older
      ages during the 21st century. As yet there is no clear way to assess senescent
      changes in humans, although activities of daily living, allostatic load, and
      frailty indices have all been suggested. One future need is greater development
      and use of universal and accessible design in all aspects of the built
      environment.

PMID- 16617217
TI  - Parental investment, late reproduction, and increased reserve capacity are
      associated with longevity in humans.
AB  - Throughout the living world trade-offs between reproductive success and longevity
      have been observed. In general, two extremes of life history patterning are
      reported, r- and K-selected species. The latter tend toward larger body sizes,
      few offspring from any one pregnancy, few offspring over the female reproductive
      span, longer life spans, and greater parental investment (PI: all efforts and
      expenses associated with the production, gestation, post-natal care, feeding, and
      protection of young) (e.g., whales, elephants, hominids). r-selected species tend
      toward smaller body size, multiple births/litters per pregnancy, female
      production of many gametes and offspring over the life span, and low levels of PI
      (e.g., most plants, insects, mice). These differences have significant influences
      on physiological variation among human populations. Across human samples,
      reproductive success (RS: the number of offspring successfully birthed and reared
      to reproductive age) has been reported to vary positively, negatively, and not at
      all with longevity of women. This complexity may be in part due to the fact that
      both early-life and late-life fecundity are associated with longevity in women,
      while total parity seems a poor gauge of female longevity in humankind. Large
      variations in associations of RS with longevity in women suggest that multiple
      factors may confound this association. One confounding factor is that among
      women, RS is largely determined not by fecundity, but by the quality of PI
      available to offspring. Among modern humans, PI is more complex, longer lasting
      (both relatively and absolutely), and extensive than for any other mammal. This
      suggests that modern human life history is a reflection of the co-evolution of
      longevity and extensive PI as part of our species' biocultural evolution. The
      need for long-term PI has greatly shaped human physiological variation and
      patterns of longevity.

PMID- 16617218
TI  - The detrimental effects of allostasis: allostatic load as a measure of cumulative
      stress.
AB  - Since its inception in the 1980s, through further developments during the 1990s,
      and continuing today, the paradigm of allostatic load (AL) has becomed an
      important paradigm for predicting senescence and mortality. AL is a cumulative
      measure of the effects of multiple stressors and the process of responding to
      stressors on the soma. AL measurements of individuals is being tested on various
      samples and species and being reported across a variety of medical and social
      science journals. From the ISI Web of Science, all articles published between
      January 2000 and June 2005 with AL in any default category were obtained and
      transferred to Endnote. These articles, categorized as theory/review or data
      driven, human or animal, and variability in risk factors used to estimate AL, are
      reviewed here. Only two of 90 reports were published in anthropological journals,
      likely, at least partly, because research on AL has focused more on western,
      industrialized populations where data are more easily obtained. From 2000-2005,
      12 of 42 data-driven reports focused on elderly humans. Studies of animal models
      also are common (0 in 2000, but 4 in 2004 covering 21 species). During the last
      year, multiple additional potential physiological variables have been tested as
      measures of AL (10 to 20 in any one article). In the past half decade, AL also
      has been introduced to a wide range of disciplines, including psychology,
      anthropology, gerontology, veterinary medicine, and medical specialties, as a
      viable research theme. AL appears to provide a useful method for determining
      cumulative somatic stress such as that seen with senescence and frailty at older
      ages.

PMID- 16617219
TI  - High-density lipoprotein cholesterol therapies: the next frontier in lipid
      management.
AB  - Current cholesterol treatment guidelines target low-density lipoprotein
      cholesterol as the primary goal of therapy and recommend statins as first line
      therapy. However, despite aggressive treatment and success at reaching the
      recommended goals, coronary heart disease is still a leading cause of morbidity
      and mortality. Thus, other lipoproteins, such as high-density lipoprotein, are
      now being looked to as the next promising targets of therapy to help reduce the
      burden of coronary heart disease and atherosclerosis. This review details
      currently available strategies to raise high-density lipoprotein cholesterol, and
      then turns to several new compounds in development that target the varying
      components of the complex metabolism of high-density lipoprotein.

PMID- 16617220
TI  - The effect of a psychosocial intervention and quality of life after acute
      myocardial infarction: the Enhancing Recovery in Coronary Heart Disease (ENRICHD)
      clinical trial.
AB  - PURPOSE: The Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD)
      clinical trial was designed to test whether intervening on depression or low
      perceived social support reduces mortality and reinfarction in patients with
      acute myocardial infarction (MI). This report analyzes the effect of the
      intervention on quality of life (QOL), which was an important secondary outcome.
      METHODS: ENRICHD was a randomized controlled clinical trial comparing a
      psychosocial intervention based on cognitive behavioral therapy to usual medical
      care in 2,481 patients from 8 clinical centers. Patients with acute MI were
      included if they met criteria for depression, low perceived social support, or
      both. QOL was assessed at the 6-month clinic visit in the first 1,296 patients.
      QOL measures included the Medical Outcomes Study Short Form summary measures of
      physical functioning (SF12-PCS) and mental functioning (SF12-MCS), a Life
      Satisfaction Scale (LSS), and a measure of overall QOL based on the ladder of
      life (LOL) technique. RESULTS: There were significant treatment differences on
      the SF12-MCS (difference 2.2, 95% confidence interval [CI] 1.2-3.2), the LSS
      (difference 1.0, 95% CI 0.5-1.5), and the LOL (difference 0.3, 95% CI 0.1-0.6),
      but not on the SF12-PCS (difference 0.8; 95% CI = -0.5-2.0). Effect sizes for the
      intervention on QOL outcomes were modest. CONCLUSIONS: Psychosocial interventions
      of limited duration confer modest QOL benefits in post-MI patients who are
      depressed or have low perceived social support. Interventions of longer duration
      or greater intensity may be required to produce more substantial improvements in
      QOL in these patients.

PMID- 16617222
TI  - A nomogram to select the optimal treadmill ramp protocol in subjects with high
      exercise capacity: validation and comparison with the Bruce protocol.
AB  - PURPOSE: Guidelines suggest that individualized ramp protocols with treadmill
      times targeted between 8 and 12 minutes are most suitable to estimate exercise
      capacity. However, previous methods to determine individualized ramp rates and
      comparisons between ramp and standardized protocols have been limited to
      clinically referred populations. METHODS: Forty-three healthy volunteers [median
      (interquartile range), age 36 (30-41) years; 10 women] performed an
      individualized ramp and a Bruce treadmill exercise protocol in random order. The
      Veterans Specific Activity Questionnaire [VSAQ, resulting in metabolic
      equivalents (METs)VSAQ] combined with a modified variant of the VSAQ nomogram
      (resulting in METs(NOMOGRAM)) was used to individualize the ramp protocol.
      Exercise capacity estimated from speed and grade of the treadmill
      (METs(ESTIMATED)) and that derived from directly measured peak oxygen uptake
      (VO2) [METs(MEASURED)] were compared with the pretest estimates of exercise
      capacity. RESULTS: Median values for METs(VSAQ), METs(NOMOGRAM), METs(ESTIMATED),
      and METs(MEASURED) for the ramp protocol were 12.0 (10-12), 15.0 (14-16.5), 16.7
      (15.9-17.8), and 15.2 (13.5-16.7), respectively. For the ramp protocol, all 43
      participants achieved a treadmill time between 8 and 12 minutes, whereas with the
      Bruce protocol only 6 (14%) participants fell within this range (P < .0001). Peak
      VO2 [ramp: 53.1 (47.4-58.3) versus Bruce: 53.5 (48.7-58.3) mL/kg/min; P = .008]
      was slightly lower using the ramp protocol. CONCLUSIONS: The modified variant of
      the VSAQ nomogram is a useful tool to estimate an individual's exercise capacity
      and to select a treadmill ramp protocol to yield the recommended exercise
      duration for moderately to highly fit, healthy individuals. The individualized
      ramp and the Bruce protocols are similar with regard to directly measured peak
      VO2 achieved.

PMID- 16617223
TI  - Short-term exercise training in patients with chronic atrial fibrillation:
      effects on exercise capacity, AV conduction, and quality of life.
AB  - PURPOSE: A randomized study was conducted to determine whether short-term
      exercise training in patients with chronic atrial fibrillation (AF) might improve
      exercise capacity and quality of life (QOL), and influence atrioventricular
      conduction. METHODS: Atrial fibrillation patients (age 64 +/- 7 years) were
      randomized to exercise training (n = 15) or a 2-month control period (n = 15)
      followed by the training program. Twenty-four training sessions consisted of
      aerobic exercise and muscle strengthening. A cycle ergometer test and a 15-minute
      resting high-frequency spectral electrocardiogram analysis were performed and a
      QOL questionnaire (SF-36) was completed before and after training. Because there
      were no changes after 2 months in the control group, pooled data for all patients
      are presented before and after training. RESULTS: Cumulated work at Borg scale 17
      increased by 41% +/- 36%. Heart rate at rest and after 10 minutes of exercise
      decreased from 75 +/- 14 to 68 +/- 14 bpm and 145 +/- 19 to 137 +/- 21 bpm,
      respectively. HF increased from 81 +/- 17 to 91 +/- 22 milliseconds. Four of the
      8 scales and 1 of the 2 summary scales of the Short-Form-36 improved. P <.05 for
      all results. CONCLUSIONS: Exercise capacity, heart rate variability, and QOL
      improved after 2 months of exercise training in patients with chronic AF. Heart
      rates at rest and during exercise decreased.

PMID- 16617224
TI  - Exercise training for patients with chronic atrial fibrillation.

PMID- 16617225
TI  - Effects of a problem-based learning rehabilitation program on physical activity
      in patients with coronary artery disease.
AB  - PURPOSE: To evaluate the effects of a problem-based learning (PBL) rehabilitation
      program on physical activity. METHODS: We randomized 207 consecutive patients
      younger than 70 years, with a recent event of coronary artery disease (CAD), to a
      PBL group (n = 104) or a control group (n = 103). In addition to standard
      treatment, the PBL patients participated in a 1-year program with 13 sessions in
      small groups, where learning needs and behavior change were focused upon.
      Physical activity was assessed by means of interviews with all patients and by an
      activity monitor in 69 patients at pretest and in 175 after 1 year. RESULTS: Only
      small differences between groups were found at posttest. Interview data revealed
      significantly less activity at low-intensity level in the control group, whereas
      the activity monitor showed no significant differences. No changes were found in
      total physical activity during the year within the 2 groups. The self-reported
      physical activity indicating a level of brisk walking was markedly higher than
      that measured by the activity monitor, the latter indicating that only 35% of the
      patients achieved a 10-minute period of continued physical activity per day on an
      adequate level. CONCLUSIONS: Our PBL program had no important impact on the
      physical activity pattern of patients with CAD. The activity monitor is a
      feasible way of measuring physical activity in these patients, indicating a lower
      level of physical activity than interview data.

PMID- 16617226
TI  - Effect of a problem-based learning rehabilitation program on physical activity in
      patients with coronary artery disease.

PMID- 16617227
TI  - Early upper-body exercise in cardiac rehabilitation after coronary artery bypass
      grafting.

PMID- 16617228
TI  - Regular walking and long-term maintenance of outcomes after pulmonary
      rehabilitation.
AB  - BACKGROUND: Empirical evidence supports the role of exercise as part of pulmonary
      rehabilitation in improving symptoms of breathlessness (dyspnea), health-related
      quality of life, and exercise tolerance among patients with chronic lung disease.
      However, many studies show that these initial benefits tend to diminish 12 to 18
      months after rehabilitation. Given the importance of exercise (ie, walking)
      during rehabilitation, we examined whether patient adherence to regular walking
      enhanced the long-term maintenance of functional benefits gained from an 8-week
      pulmonary rehabilitation program. METHODS: One hundred twenty-three patients with
      moderate to severe chronic lung disease completed an 8-week pulmonary
      rehabilitation program and participated in a 12-month maintenance intervention
      trial. Measures of weekly walking, lung function, self-efficacy for walking,
      dyspnea during activities of daily living, exercise capacity (6-minute walk test,
      6MW), perceived breathlessness after the 6MW, and health-related quality of life
      were obtained at postrehabilitation, and at 6, 12, and 24 months after completing
      pulmonary rehabilitation. Regular walkers were defined as those active on most
      days or every single day of the week on the average throughout the 24-month
      period, whereas irregular walkers walked on some days, rarely, or not at all.
      RESULTS: The effects of the maintenance program on average frequency of walking
      were nonsignificant, with 44% of the maintenance patients and 38% of the standard
      care patients classified as regular walkers. There were no significant
      differences between walking groups on gender, healthcare utilization over the 24
      month follow-up period, and postrehabilitation measures of lung function, 6MW
      distance, perceived breathlessness after 6MW, health-related quality of life,
      dyspnea, or age. Repeated measures analyses of variance using a 2 x 4 mixed model
      approach were applied to examine group differences and changes in outcomes over
      time. Overall, participants decreased in 6MW distance (P <.001), reported
      increases in perceived breathlessness after the 6MW (P <.05), and decreased in
      overall health-related quality of life (P <.001) from postrehabilitation to 24
      months. Regular walkers reported significantly better health-related quality of
      life (P <.05) as compared to irregular walkers, averaging across time points.
      Irregular walkers declined significantly more than regular walkers on measures of
      shortness of breath during activities of daily living (P <.01) and walking self
      efficacy (P <.001) from postrehabilitation to 24 months. CONCLUSIONS: Findings
      suggest that participation in regular exercise such as walking after completing
      pulmonary rehabilitation is associated with slower declines in overall health
      related quality of life and walking self-efficacy as well as less progression of
      dyspnea during activities of daily living. Regular exercise after rehabilitation
      may be protective against increases in dyspnea symptoms and perceived limitations
      in walking which are both characteristic of progressing chronic lung disease.

PMID- 16617229
TI  - Results of an 8-week, outpatient pulmonary rehabilitation program on patients
      with and without chronic obstructive pulmonary disease.
AB  - PURPOSE: To determine whether there is any difference in the effect of pulmonary
      rehabilitation (PR) on outcomes in patients with and without chronic obstructive
      pulmonary disease (COPD). METHODS: Retrospective analysis of medical records of
      all patients enrolling in PR over a 5-year period. RESULTS: A total of 422
      patients enrolled in a multidisciplinary PR program from August 1999 to April
      2004. Three hundred nine patients had COPD and 113 patients had diagnoses other
      than COPD. Three hundred seventy-nine patients completed the program. PR was
      conducted according to currently accepted guidelines. Measurements included the 6
      minute walk distance (6MW) performed at the beginning and end of the program and
      quality of life as determined by the Chronic Respiratory Questionnaire (CRQ) at
      the beginning and end of the program. Both groups had significant improvements in
      the 6MW and all domains of the CRQ following PR. There was no significant
      difference in any of these outcomes between the 2 groups. The baseline forced
      expiratory volume in 1 second (FEV1) was not correlated with improvement in the
      6MW in either group. CONCLUSIONS: There is no significant difference in
      improvement in exercise tolerance or quality of life following PR in COPD versus
      non-COPD patients. Baseline lung function does not predict improvement in
      exercise tolerance. PR is effective for patients with disability due to any
      chronic respiratory disease and not just COPD.

PMID- 16617231
TI  - Overweight and obesity: prevalence, consequences, and causes of a growing public
      health problem.
AB  - This paper provides an overview of the evidence on the current epidemic of
      obesity in the United States. The prevalence of overweight and obesity now
      exceeds 60% among US adults, and the rate is rapidly increasing among children
      and adolescents. Dismal medical, social, and economic consequences are already
      apparent and likely to worsen without multipronged intervention. Increased rates
      of hypertension, diabetes, and dyslipidemia, among other medical conditions,
      threaten to shorten the longevity of the American populace by as much as 5 years.
      The incidence of depression is increasing and experts suggest this is linked with
      the increased prevalence of obesity. The cost of obesity-related medical care has
      increased astronomically since 1987, in addition to lost productivity and income.
      Novel multidisciplinary, preventive, and therapeutic approaches, and social
      changes are needed that address the complex interplay of biologic, genetic, and
      social factors that have created the current obesity epidemic.

PMID- 16617232
TI  - A clinician's approach to medical management of obesity.
AB  - Obesity is pandemic in the modern world and continues to increase at an alarming
      rate, with great human and economic consequences. While bariatric surgery has
      been gaining popularity and acceptance as an effective way to achieve massive
      weight loss, it remains an option only for the extremely obese. For the millions
      of overweight and moderately obese individuals, the cornerstone of obesity
      treatment remains lifestyle and behavioral modifications in diet and physical
      activity. It is especially important for both primary care providers and
      subspecialists to be familiar with currently recommended approaches to the
      medical treatment of obesity, as it is critical that this extremely common,
      treatable chronic disease be recognized, intervention initiated, and therapy
      maintained at every appropriate clinical opportunity. Significant medical
      benefits can be gained even with a relatively small percentage of weight loss.

PMID- 16617233
TI  - The effect of obesity surgery on obesity comorbidity.
AB  - Obesity is epidemic in the modern world. It is becoming increasingly clear that
      obesity is a major cause of cardiovascular disease, diabetes, and renal disease,
      as well as a host of other comorbidities. There are at present no generally
      effective long-term medical therapies for obesity. Surgical therapy for morbid
      obesity is not only effective in producing long-term weight loss but is also
      effective in ameliorating or resolving several of the most significant
      complications of obesity, including diabetes, hypertension, dyslipidemia, sleep
      apnea, gastroesophageal reflux disease, degenerative joint disease, venous
      stasis, pseudotumor cerebri, nonalcoholic steatohepatitis, urinary incontinence,
      fertility problems, and others. The degree of benefit and the rates of morbidity
      and mortality of the various surgical procedures vary according to the procedure.

PMID- 16617234
TI  - Bariatric surgery: past and present.
AB  - Bariatric operations are either restrictive, limiting the amount of food
      ingested; malabsorptive, limiting the amount of nutrient absorbed; or a
      combination of both. Bariatric surgery dates back to the 1950s when jejunoileal
      bypass was introduced. Since then, numerous improvements have been made in
      procedures and techniques. Currently, the two most common bariatric procedures
      performed are laparoscopic adjustable gastric banding and laparoscopic Roux-en-Y
      gastric bypass. Both of these operations provide excellent results, with the
      majority of patients losing more than 50% of their excess weight and with most
      obesity-related comorbidities such as diabetes and hypertension reversed or
      prevented. Morbidly obese patients considering such operations have to meet
      strict criteria and must be evaluated by a multidisciplinary team. They need to
      commit to long-term dietary changes, behavioral modifications, and medical
      supervision. The choice of procedure is guided by multiple factors, including the
      patient's and the surgeon's preference.

PMID- 16617235
TI  - Psychological assessment and management of the weight loss surgery patient.
AB  - Psychological evaluation of the weight loss surgery patient is recommended
      because of the prevalence of psychiatric comorbidities in persons with severe
      obesity and the behavioral adaptations required for successful surgical outcomes.
      Although there is currently no national standard for the specific components of
      these evaluations, there is general agreement in the literature about the
      objectives and the kinds of assessment methods that are most useful. This paper
      summarizes the current literature on psychological evaluation of weight loss
      surgery patients. Methods of assessment relevant to the major behavioral health
      characteristics of surgical candidates are reviewed, and results from several
      studies examining weight loss and quality of life outcomes in relation to pre
      surgery psychological characteristics are discussed.

PMID- 16617236
TI  - Nutritional management of patients after bariatric surgery.
AB  - Bariatric surgery is currently the most effective method of sustainable weight
      loss among morbidly obese patients. The types of bariatric surgeries can be
      divided into three categories: restrictive procedures, malabsorptive procedures,
      and combination (restrictive and malabsorption) procedures. In general, patients
      undergoing restrictive procedures have the least risk for long-term diet-related
      complications, whereas patients undergoing malabsorptive procedures have the
      highest risk. For many patients, the benefits of weight loss, such as decreased
      blood glucose, lipids, and blood pressure and increased mobility, will outweigh
      the risks of surgical complications. Most diet-related surgical complications can
      be prevented by adhering to strict eating behavior guidelines and supplement
      prescriptions. Eating behavior guidelines include restricting portion sizes,
      chewing foods slowly and completely, eating and drinking separately, and avoiding
      foods that are poorly tolerated. Supplement prescriptions vary among
      practitioners and usually involve at least a multivitamin with minerals. Some
      practitioners may add other supplements only as needed for diagnosed
      deficiencies; others may prescribe additional prophylactic supplements. The most
      common nutrient deficiencies are of iron, folate, and vitamin B12. However,
      deficiencies of fat-soluble vitamins have been reported in patients with
      malabsorption procedures, and thiamin deficiency has been reported among patients
      with very poor intake and/or nausea and vomiting. Frequent monitoring of
      nutrition status for all patients can aid in preventing severe clinical
      deficiencies.

PMID- 16617237
TI  - Gastrointestinal complications of bariatric surgery: diagnosis and therapy.
AB  - Severe or morbid obesity, with body mass indexes exceeding 35 to 40, are often
      refractory to all therapies other than surgery. The increasing number of patients
      undergoing bariatric surgery will result in increasing numbers of patients with
      gastrointestinal complications. The types of complications vary with type of
      surgery, whether restrictive, malabsorptive, or both, depending on what
      anatomical and physiologic changes occur postoperatively. One complication of
      bariatric surgery (gallstones) is due to weight loss after surgery, not the
      surgery itself. Based on previous meta-analyses, most of the top 10 complications
      from bariatric surgery are gastrointestinal: dumping, vitamin/mineral
      deficiencies, vomiting (and nausea), staple line failure, infection, stenosis
      (and bowel obstruction), ulceration, bleeding, splenic injury, and perioperative
      death. Two other gastrointestinal complications of bariatric surgery are indirect
      consequences of the surgery: bacterial overgrowth and diarrhea. Awareness of the
      types and frequency of gastrointestinal complications of bariatric surgery allows
      for timely diagnosis and appropriate therapy. As new surgical, and even
      endoscopic, procedures to treat obesity are developed, new gastrointestinal
      complications will need to be recognized.

PMID- 16617238
TI  - Nutritional and metabolic complications of bariatric surgery.
AB  - Bariatric surgery is an effective treatment for patients with clinically severe
      obesity. In addition to significant weight loss, it is also associated with
      improvements in comorbidities. Unfortunately, bariatric surgery also has the
      potential to cause a variety of nutritional and metabolic complications. These
      complications are mostly due to the extensive surgically induced anatomical
      changes incurred by the patient's gastrointestinal tract, particularly with roux
      en-Y gastric bypass and biliopancreatic diversion. Complications associated with
      vertical banded gastroplasty are mostly due to decreased intake amounts of
      specific nutrients. Macronutrient deficiencies can include severe protein-calorie
      malnutrition and fat malabsorption. The most common micronutrient deficiencies
      are of vitamin B12, iron, calcium, and vitamin D. Other micronutrient
      deficiencies that can lead to serious complications include thiamine, folate, and
      the fat-soluble vitamins. Counseling, monitoring, and nutrient and mineral
      supplementation are essential for the treatment and prevention of nutritional and
      metabolic complications after bariatric surgery.

PMID- 16617239
TI  - Looking to the future: electrical stimulation for obesity.
AB  - Among all classes of therapies for morbid obesity-behavioral, drugs, devices, and
      surgery-devices for electrical stimulation are a relatively new approach. This
      article reviews the history of electrical therapies for the gastrointestinal
      tract with an emphasis on the development of stimulation for obesity. Based on
      similar animal work, electrical stimulation of the gastrointestinal tract has
      been applied to treat morbid obesity much in the way it has been used to treat
      nausea and vomiting. The current status of gastrointestinal electrical
      stimulation for the treatment of morbid obesity is reviewed, with an emphasis on
      human studies. The physics of electrical stimulation and the possible mechanism
      of stimulation in the gastrointestinal tract, including for the treatment of
      morbid obesity, are also discussed. Future work on stimulation for obesity offers
      the opportunity for better understanding of possible mechanisms of action.

PMID- 16617240
TI  - The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: an update.
AB  - The most common fatty acid oxidation disorder, medium chain acyl-CoA
      dehydrogenase deficiency (MCADD), has become the focal point for the adoption of
      tandem mass spectrometry to detect it and related inborn errors of metabolism.
      This article updates a human genome epidemiology review of MCADD published in
      1999. The focus of this update is on epidemiologic parameters rather than
      mutations associated with MCADD. Currently available information from screening
      studies on the frequency of detection of MCADD in newborns, as well as the
      frequency of homozygotes for the common mutation in the ACADM gene, is
      summarized. In the United States, the average incidence of the disorder is from 1
      in 15,000 to 1 in 20,000 births, with individual states reporting frequencies
      from 1 in 10,000 to 1 in 30,000 births. In addition, a systematic review was
      undertaken of the published literature on the frequency of mortality and
      developmental disabilities among children with MCADD, both in screened and
      unscreened cohorts. It seems that in the absence of newborn screening for MCADD,
      premature death or serious disability occurs in 20% to 25% of children with the
      disorder. Systematic collection and analysis of follow-up data are still needed
      to ascertain the frequencies of outcomes in screened cohorts.

PMID- 16617241
TI  - The versatile RECQL4.
AB  - The human DNA helicase RECQL4 interacts in an array of intracellular regulatory
      pathways from the initiation of DNA replication, through maintaining genomic
      stability, to the N-end rule pathway. Interestingly, mutations in RECQL4 have
      recently been revealed not only in Rothmund-Thomson-, but RAPADILINO-, and cases
      of Baller-Gerold syndrome also. Although these disorders represent distinct
      genetic entities, clinical observations have delineated highly variable
      expressivity and significant overlaps in the associated phenotypic
      manifestations. Consequently, it is especially difficult to draw precise genotype
      phenotype correlations in RECQL4 related syndromes. This is likely due to the
      complex and multiple cellular networks RECQL4 is associated with.

PMID- 16617242
TI  - OPA1 mutations and mitochondrial DNA haplotypes in autosomal dominant optic
      atrophy.
AB  - PURPOSE: Autosomal dominant optic atrophy is a form of blindness, due in part to
      mutations affecting the mitochondrial-targeted OPA1 gene product. Both OPA1
      positive and OPA1-negative families exhibit variable expressivity and incomplete
      penetrance. The purpose of this study was therefore to determine if the
      background mtDNA genotype acts as a genetic modifier for the expression of this
      disease. METHODS: To find novel pathogenic OPA1 mutations, we performed complete
      OPA1 gene exon sequencing in 30 patients. To assess the possibility that
      mitochondrial DNA haplotype acts as a genetic modifier, we determined the
      mitochondrial DNA haplotype in 29 Caucasian OPA1-positive and OPA1-negative
      patients. Deviations in haplotype distribution between patient and control groups
      were determined by statistical means. RESULTS: Seven new pathogenic OPA1
      mutations were found. Most were detected in the mitochondrial targeting N
      terminus or in the coiled-coil domain at the C-terminus. Mitochondrial DNA
      haplotype analysis indicated that the European haplogroup distribution was
      different between Caucasian patients and controls. Further, haplogroup J was
      three-fold over-represented in OPA1-negative patients. CONCLUSIONS: Overall, our
      results support haploinsufficiency as a genetic mechanism in OPA1-positive cases
      and also suggest that mtDNA genetic background may influence disease expression
      in a subset of cases.

PMID- 16617243
TI  - Evaluation of a decision aid for families considering p53 genetic counseling and
      testing.
AB  - PURPOSE: Li-Fraumeni syndrome (LFS) is associated with p53 germline mutations,
      and carriers are at increased risk for multiple primary cancers. We evaluated
      outcomes following the administration of a video-based decision aid (DA) prior to
      clinical p53 genetic counseling and testing among persons who had previously
      participated in cancer genetics research. METHODS: Fifty-seven individuals at
      risk for a known p53 mutation completed baseline and post-DA measures of
      psychological outcomes, plus knowledge and attitudes regarding p53 genetic
      testing. Counseling and testing uptake also was recorded. RESULTS: At baseline,
      multivariate analysis showed that greater testing intention was associated with
      lower decisional conflict (P < 0.01). Compared with baseline data, multivariate
      analyses of post-DA outcomes showed that knowledge about LFS and genetic testing
      increased and decisional conflict related to testing decreased (P < 0.001). Mean
      cancer worries scores decreased among all participants (P < 0.001), and mean
      depression scores decreased for males (P < 0.05). Thirty-nine (68%) completed pre
      test genetic counseling and 23 (40%) subsequently gave a blood sample for
      clinical genetic testing. CONCLUSION: This intervention was useful as an initial
      outreach and educational method for families considering p53 genetic testing, and
      may improve knowledge about LFS as well as psychological outcomes.

PMID- 16617244
TI  - How does the mode of inheritance of a genetic condition influence families? A
      study of guilt, blame, stigma, and understanding of inheritance and reproductive
      risks in families with X-linked and autosomal recessive diseases.
AB  - PURPOSE: While the mode of inheritance of a genetic condition has long been
      considered to have not only medical, but also psychosocial consequences for
      families, this supposition has never been tested. METHODS: We surveyed 112
      members of 51 families (59% response) with chronic granulomatous disease to
      determine the influence of mode of inheritance on parents', siblings', and
      patients' (1) knowledge of inheritance and reproductive risk; (2) concern about
      risk to future family-members; (3) feelings of guilt and blame; and (4) feelings
      of stigmatization. Ninety-six members of 51 families (49% response) with
      Duchenne/Becker muscular dystrophy and spinal muscular atrophy types II/III were
      also studied. RESULTS: X-linked families had better understanding of inheritance
      (P < 0.001) and reproductive risks (P < 0.01). X-linked mothers worried more
      about risks to future generations; other autosomal-recessive family members were
      as worried. X-linked mothers were more likely to feel guilty (P < 0.01) and blame
      themselves (P < 0.001). X-linked fathers blamed their child's mother (P < 0.05)
      and X-linked mothers felt more blamed by the father (P < 0.01). X-linked family
      members were more likely to consider being a carrier stigmatizing (P < 0.05).
      CONCLUSION: When providing genetic counseling, attention should be given to guilt
      and blame in X-linked families and understanding reproductive risks in autosomal
      recessive families.

PMID- 16617246
TI  - Haploinsufficiency due to deletion within the 3'-UTR of C1-INH-gene associated
      with hereditary angioedema.
AB  - PURPOSE: Sequences within the non-coding 3'UTR (untranslated region) of genes
      were reported to be involved in the regulation of gene expression by modifying
      pathways of (co)transcription, post-transcriptional processing and RNA transport.
      However, direct biological evidence (i.e., knock-out models) is sparse. This
      report intends to correlate the first reported alteration within the 3'UTR of the
      C1 inhibitor (C1-INH) gene with clinical presentation of hereditary angioedema
      (HAE). METHODS AND RESULTS: Direct sequencing of genomic DNA revealed in all
      affected members of a family suffering from HAE a heterozygous 155 bp deletion
      100 bp downstream of the physiological stop-codon in exon 8. A substantial
      reduction of both mRNA as well as C1-INH protein expression was revealed by RT
      PCR and nephelometry, respectively. CONCLUSION: We suppose that the mutation
      within the 3'UTR interferes with integral pathways of gene expression leading to
      pathogenic haploinsufficiency in this family.

PMID- 16617245
TI  - C-reactive protein levels in subjects with Prader-Willi syndrome and obesity.
AB  - PURPOSE: Prader-Willi syndrome is characterized by infantile hypotonia, feeding
      difficulties, hypogonadism, small hands and feet, mental deficiency, behavioral
      problems, and hyperphagia leading to obesity in early childhood. To date there
      have been no studies examining the associated risk of cardiovascular disease
      related to obesity in Prader-Willi syndrome, nor of circulating biomarkers such
      as C-reactive protein known to be predictive of cardiovascular disease.
      Therefore, we have measured the levels of C-reactive protein in a descriptive
      study of a cohort of Prader-Willi syndrome and comparison subjects. METHODS: An
      immunoassay was used to quantify C-reactive protein in plasma samples from
      subjects with Prader-Willi syndrome and obesity and compared to anthropometric
      and body composition data. RESULTS: The mean circulating C-reactive protein
      concentration for 28 subjects with Prader-Willi syndrome (13 females, 15 males;
      mean age 24.6 +/- 11.6 years; mean body mass index 35.9 +/- 11.9) was 10.3 +/-
      8.8 mg/L. The mean C-reactive protein concentration for 22 nonsyndromic obese
      subjects (16 females, 6 males; mean age 32.3 +/- 12.2 years; mean body mass index
      36.6 +/- 10.7) was 8.8 +/- 10.9 mg/L. The reported mean value for C-reactive
      protein was 2.6 +/- 3.0 mg/L from 100 healthy adults. CONCLUSIONS: The mean C
      reactive protein values were similar between the subjects with Prader-Willi
      syndrome and obesity but significantly higher in Prader-Willi syndrome and obese
      subjects relative to normative data. Increased levels of C-reactive protein (>3.0
      mg/L) are associated with cardiovascular disease suggesting subjects with Prader
      Willi syndrome as well as obese subjects are at a similar increased risk.

PMID- 16617247
TI  - Cystic Fibrosis testing among Arab-Americans.
AB  - PURPOSE: Limited data regarding the cystic fibrosis carrier frequency and
      mutation detection rate is available for Arab-Americans. We retrospectively
      determined the frequency of carriers among Arab-Americans undergoing
      preconception and prenatal carrier screening in our laboratories. METHODS:
      Between October, 2001 and June, 2005, we performed carrier screening on 805 Arab
      Americans, testing for at least the original 25 mutations recommended by the
      American College of Medical Genetics. We compared our results to previously
      published studies among Arabic cystic fibrosis patients. We also performed
      diagnostic testing on seven individuals. RESULTS: Seven carriers were identified,
      with an observed carrier frequency of 1 in 115. The most common mutation we
      identified was W1282X (57% of the mutations detected), followed by DeltaF508 and
      R117H. Three of 7 patients with a known or suspected diagnosis had two
      identifiable mutations, including 1548delG, DeltaF508, W1282X, 2789 + 5G>A and
      R170H. CONCLUSION: The current recommended carrier screening panel includes only
      six mutations reported among Arabic cystic fibrosis patients, accounting for
      37.1% of the mutations identified among this group. The addition of 1548delG,
      I1234V, H139L and 4010del4 as part of an extended screening panel would increase
      the detection rate to 66.3%, similar to the mutation detection rates in other
      races/ethnic groups.

PMID- 16617248
TI  - Two independent mutations of the SMN1 gene in the same spinal muscular atrophy
      family branch: lessons for carrier diagnosis.
AB  - PURPOSE: We present the results of carrier studies in 33 relatives of the
      paternal branch of a spinal muscular atrophy patient with homozygous absence of
      the SMN1 gene. METHODS AND RESULTS: Once linkage and quantitative analyses were
      performed, a number of first-, second- and third-degree relatives were identified
      as carriers given that they shared the at-risk haplotype and showed one SMN1
      copy. In the fourth-degree relatives, linkage analysis demonstrated discordance
      with the quantitative results because the members with one copy were carriers of
      the mutation, but in a different haplotype background. We concluded that two
      independent mutations were present in this branch of the family. Furthermore, the
      combination of both methods of analysis allowed us to identify carriers with two
      SMN1 genes in one chromosome and none in the remaining chromosome. CONCLUSIONS:
      Carrier testing in spinal muscular atrophy should be performed by employing both
      quantitative and linkage analyses in order to guarantee accurate carrier
      identification.

PMID- 16617249
TI  - Prevention of mental retardation: what do health professionals and general
      population know about this issue?

PMID- 16617250
TI  - Probability in gene expression.

PMID- 16617252
TI  - Anemia and perioperative red blood cell transfusion: a matter of tolerance.
AB  - In the past, anemia in the perioperative period has been treated by red blood
      cell (RBC) transfusions relatively uncritically. RBC transfusions were believed
      to increase oxygen delivery by increasing hemoglobin concentration. Arbitrary
      transfusion triggers such as the "10/30 rule" (i.e., RBC transfusion indicated
      below a hemoglobin concentration of 10 g/dL or a hematocrit of 30%) were applied.
      However, there is now increasing evidence that RBC transfusions are associated
      with adverse outcomes and should be avoided whenever possible. Restraining from
      RBC transfusions and maintaining normovolemia in patients suffering from surgical
      blood loss results in acute anemia. Therefore, knowing the compensatory
      mechanisms during acute anemia is crucial. This review focuses on acute anemia
      tolerance, its limits, and physiologic transfusion triggers in the perioperative
      period.

PMID- 16617253
TI  - Pulmonary edema after transfusion: how to differentiate transfusion-associated
      circulatory overload from transfusion-related acute lung injury.
AB  - OBJECTIVE: Pulmonary edema is an under-recognized and potentially serious
      complication of blood transfusion. Distinct mechanisms include adverse immune
      reactions and circulatory overload. The former is associated with increased
      pulmonary vascular permeability and is commonly referred to as transfusion
      related acute lung injury (TRALI). The latter causes hydrostatic pulmonary edema
      and is commonly referred to as transfusion-associated circulatory overload
      (TACO). In this review article we searched the National Library of Medicine
      PubMed database as well as references of retrieved articles and summarized the
      methods for differentiating between hydrostatic and permeability pulmonary edema.
      RESULTS: The clinical and radiologic manifestations of TACO and TRALI are
      similar. Although echocardiography and B-type natriuretic peptide measurements
      may aid in the differential diagnosis between hydrostatic and permeability
      pulmonary edema, invasive techniques such as right heart catheterization and the
      sampling of alveolar fluid protein are sometimes necessary. The diagnostic
      differentiation is especially difficult in critically ill patients will multiple
      comorbidities so that the cause of edema may only be determined post hoc based on
      the clinical course and response to therapy. Guided by available evidence, we
      present an algorithm for establishing the pretest probability of TRALI as opposed
      to TACO. The decision to test donor and recipient blood for immunocompatibility
      may be made on this basis. CONCLUSIONS: The distinction between hydrostatic
      (TACO) and permeability (TRALI) pulmonary edema after transfusion is difficult,
      in part because the two conditions may coexist. Knowledge of strengths and
      limitations of different diagnostic techniques is necessary before initiation of
      complex TRALI workup.

PMID- 16617254
TI  - Transfusion-related acute lung injury (TRALI): clinical presentation, treatment,
      and prognosis.
AB  - The term transfusion-related acute lung injury (TRALI) was coined in 1983 to
      describe a constellation of clinical and laboratory features seen within 6 hrs of
      the transfusion of plasma-containing blood products. These products contain
      antibodies directed to human leukocyte antigens (and subsequently described to
      nonhuman leukocyte antigens) found on white blood cells. In the intervening 2
      decades, other cases not associated with antibodies have been reported as TRALI
      and an association with passive infusion of lipids accumulated in stored cellular
      blood products has been made in those cases. This has led to confusion as to what
      should be considered to constitute TRALI. Therefore, the true incidence of this
      pulmonary reaction to blood products is currently conjectural at best. Recent
      consensus development conferences have been held to develop and standardize
      definitions of TRALI so that epidemiologic and research aspects of this condition
      can be explored in a scientific manner. These conferences have set out criteria
      by which TRALI is distinguished from other causes of acute lung injury. This
      review outlines the widely accepted clinical (mainly pulmonary) features of
      TRALI, the treatment options, and the excellent long-term prognosis for patients
      who survive the initial pulmonary insult.

PMID- 16617255
TI  - Mechanisms of transfusion-related acute lung injury (TRALI): anti-leukocyte
      antibodies.
AB  - There is abundant evidence that leukocyte antibodies in blood donor products are
      somehow involved in transfusion-related acute lung injury (TRALI). Human
      leukocyte antigen (HLA) class I, HLA class II, and neutrophil-specific antibodies
      in the plasma of both blood donors and recipients have been implicated in the
      pathogenesis of TRALI. The case for a relationship between leukocyte antibodies
      and TRALI is more compelling if concordance between the antigen specificity of
      the leukocyte antibodies in the donor plasma and the corresponding antigen on the
      cells of the affected recipient is demonstrated. Such antibody-antigen
      concordance can be investigated by typing the recipient for the cognate leukocyte
      antigens or by cross-matching the donor plasma against the recipient's
      leukocytes. Two proposed pathophysiologic mechanisms for TRALI have received the
      most attention: the antibody hypothesis and the two-event hypothesis. The final
      common pathway in all of the proposed pathogenic mechanisms of TRALI is increased
      pulmonary capillary permeability, which results in movement of plasma into the
      alveolar space causing pulmonary edema. A typical TRALI serologic workup consists
      of tests for HLA class I and II and neutrophil-specific antibodies. The use of
      flow cytometry and HLA-coated microbeads is recommended for detection of HLA
      antibodies in plasma of implicated blood donors and a combination of the
      granulocyte agglutination test and granulocyte immunofluorescence test for
      detection of neutrophil-specific antibodies. Genotyping for class I and II HLA
      and for a limited number of neutrophil antigens may also be helpful in
      establishing antibody-antigen concordance.

PMID- 16617256
TI  - The two-event model of transfusion-related acute lung injury.
AB  - The objective of this review is to present the two-event model of transfusion
      related acute lung injury (TRALI), a life-threatening complication of
      transfusions that has been the most common cause of transfusion-related death
      over the past 2 yrs in the United States. The two-event model of TRALI, which is
      identical to the pathogenesis of the acute respiratory distress syndrome (ARDS),
      is reviewed and contrasted to antibody-mediated TRALI. Laboratory studies, both
      in vitro and in vivo, are discussed as well as human studies of TRALI. Methods to
      avoid patient exposure to blood components that may cause TRALI are also
      discussed.

PMID- 16617258
TI  - Blood donor and component management strategies to prevent transfusion-related
      acute lung injury (TRALI).
AB  - OBJECTIVE: Discuss the pros and cons of using donor and blood product-management
      strategies to prevent transfusion-related acute lung injury (TRALI). DATA SOURCE:
      A review of the literature was performed. RESULTS: Despite therapeutic advances
      in pulmonary and critical care medicine, TRALI is now considered to be one of the
      leading causes of transfusion-associated mortality, and thus determining how to
      prevent TRALI is extremely important. Donor and product-management strategies to
      prevent this life-threatening condition have been suggested, but because of gaps
      in our understanding of TRALI, blood-bankers do not know how beneficial these
      interventions will be, nor the amount of potential harm-such as decreasing the
      availability of blood-that could arise if they were implemented. This article
      discusses the advantages and disadvantages of the various preventive measures
      that have been described in the literature. CONCLUSIONS: Preventing TRALI poses a
      difficult challenge for blood-banking experts, because it is unknown which
      measures will be effective in decreasing the incidence of TRALI and which could
      have significant drawbacks. Only additional research into TRALI prevention will
      provide the answers on how to best protect patients from this potentially fatal
      reaction.

PMID- 16617257
TI  - Animal models of transfusion-related acute lung injury.
AB  - OBJECTIVE: To examine the existing animal models of transfusion-related acute
      lung injury (TRALI) for insight into disease pathogenesis. DATA SOURCE: The data
      were taken from published research and from our own experimental results.
      RESULTS: Animal models have disproved the microaggregate theory of acute lung
      injury from blood transfusions. The two major hypotheses of TRALI, passively
      transfused neutrophil and human leukocyte antigen antibodies and biologically
      active lipids that accumulate in older, cellular blood products, have been
      replicated in animal models. The proposed two-hit model of TRALI is also
      supported by animal studies. A new in vivo mouse model of TRALI based on major
      histocompatibility complex (MHC) I antibodies has replicated several features of
      human TRALI, focusing prominently on the role of neutrophils. CONCLUSIONS:
      Experimental animal models support both the antibody and lipid theories of TRALI.
      The essential role of neutrophils to producing lung injury is common to all
      existing models of TRALI. There is a lack of clinically relevant animal models
      that explain why transfusion of donor antibodies to cognate antigens in the
      recipient does not always lead to TRALI.

PMID- 16617259
TI  - Massive transfusion as a risk factor for acute lung injury: association or
      causation?
AB  - One of the most common clinical sequelae of massive transfusion is acute lung
      injury. In virtually all clinical settings, there is a very strong relationship
      between transfusion and acute lung injury that remains even after adjusting for
      potential confounders. Whether the association between transfusion and acute lung
      injury in these settings is a result of residual confounding or actually reflects
      a causal relationship is unknown. However, there are several potential mechanisms
      by which massive transfusion might predispose to lung injury: a) cognate antigen
      antibody interactions (classic transfusion-associated lung injury); b) activation
      of nonspecific immunity through soluble mediators present in transfused blood; c)
      an increased risk of infection through transfusion-associated immunomodulation
      leading to sepsis and sepsis-induced lung injury; and d) volume overload in the
      face of increased permeability of the alveolar capillary membrane. Elucidating
      the precise causal mechanism operative in patients receiving massive transfusion
      has more than academic importance; it has direct implications for transfusion
      policy and practice.

PMID- 16617260
TI  - Pneumonia as a complication of blood product transfusion in the critically ill:
      transfusion-related immunomodulation (TRIM).
AB  - BACKGROUND: An increased risk of postoperative infection (including pneumonia)
      attributable to the receipt of allogeneic blood transfusion has been investigated
      as a possible manifestation of transfusion-related immunomodulation (TRIM) in 16
      randomized controlled trials (RCTs) and approximately 40 observational studies.
      OBJECTIVES: This review categorizes RCTs and observational studies with regard to
      the inference that they permit about possible mediators of TRIM-allogeneic white
      cells (WBCs), WBC-derived soluble mediators, and/or allogeneic plasma-and
      examines whether the totality of the clinical evidence supports an association
      between allogeneic blood transfusion and postoperative infection. RESULTS: When
      all available studies are considered together in meta-analyses, three types of
      studies show no increased risk of postoperative infection in association with
      allogeneic blood transfusion: a) RCTs comparing recipients of buffy-coat-reduced
      and prestorage-filtered, WBC-reduced allogeneic red cells; b) RCTs comparing
      recipients of allogeneic and autologous blood; and c) observational studies
      comparing patients transfused before and after implementation of WBC reduction.
      RCTs comparing recipients of nonbuffy-coat-reduced and WBC-reduced red blood
      cells may point to a TRIM effect, but they cannot yet be subjected to formal meta
      analysis. CONCLUSIONS: No overwhelming clinical evidence has been presented to
      establish the existence of a TRIM effect that relates allogeneic blood
      transfusion to postoperative infection.

PMID- 16617261
TI  - Alternatives to blood product transfusion in the critically ill: erythropoietin.
AB  - OBJECTIVE: To present information regarding the use of recombinant human
      erythropoietin (rHuEPO) to treat anemia in intensive care unit (ICU) patients
      MAIN RESULTS: Anemia is common in critically ill patients. Approximately 95% of
      patients have subnormal hemoglobin (Hb) values by day 3 of their ICU stay. ICU
      associated anemia often requires replacement of red blood cells (RBCs) via
      transfusion. Recent surveys of ICU practice document that approximately 50% of
      ICU patients receive RBC transfusions. ICU-associated anemia is largely the
      result of the cumulative effects of blood loss and decreased RBC production.
      Blood loss in critically ill patients may be overt, occult, or due to phlebotomy.
      Decreased RBC production is the other major factor influencing the development of
      anemia. Decreased RBC production is due to the combined effects of abnormal iron
      metabolism, inappropriately low erythropoietin production, diminished response to
      erythropoietin, and direct suppression of RBC production. Inflammatory mediators
      play a pivotal role in the pathogenesis of decreased RBC production. Clinical
      trials have shown that, compared with nontreated subjects, rHuEPO-treated ICU
      patients will have increased serum erythropoietin concentrations, increased
      reticulocyte counts, and increased hemoglobin and hematocrit values and require
      fewer RBC transfusions. These clinical trials have not detected significant
      differences in outcomes in association with rHuEPO, however. CONCLUSIONS: rHuEPO
      can be used to increase hemoglobin and hematocrit values and decrease the number
      of RBC transfusions in ICU patients. Further investigation is necessary to
      identify the appropriate target population of ICU patients for treatment, to
      clarify the appropriate dosing schedule, and to ascertain whether such therapy
      has a positive impact on outcomes.

PMID- 16617262
TI  - Fresh frozen plasma and platelet transfusion for nonbleeding patients in the
      intensive care unit: benefit or harm?
AB  - OBJECTIVE: Whereas restrictive red cell transfusion has become a standard of care
      for the critically ill, evidenced-based indications for use of other blood
      components such as fresh frozen plasma (FFP) and platelet transfusions are
      limited. We searched the National Library of Medicine PubMed database as well as
      references of retrieved articles and summarized the current evidence for the use
      of FFP and platelet transfusions in critically ill patients. RESULTS: Routine
      coagulation tests are poor determinants of bleeding risk in critically ill
      patients with coagulopathy. FFP transfusion has limited efficacy and is
      associated with significant morbidity in critically ill patients, in particular,
      pulmonary edema and acute lung injury. Routine minimally invasive critical care
      procedures can be safely performed by experienced clinicians in the setting of
      mildly abnormal coagulation test results, and there is no evidence that FFP
      transfusion alters the risk of bleeding. For platelet transfusion, the American
      Society of Clinical Oncology has developed practice guidelines designed for
      oncology patients. However, because the pathophysiology of thrombocytopenia in
      critically ill patients often differs from that of thrombocytopenia in oncology
      patients, published guidelines for oncology patients may not be applicable.
      CONCLUSION: Because the risk-benefit ratio of a liberal FFP or platelet
      transfusion strategy for critically ill patients may not be favorable, randomized
      controlled trials are warranted for evaluating a restrictive vs. liberal FFP or
      platelet transfusion strategy for nonbleeding patients in the intensive care
      unit.

PMID- 16617264
TI  - Transfusion in the intensive care unit.
AB  - OBJECTIVE: To summarize the incidences of anemia and blood transfusions in
      critically ill patients, assess their comparative risks and benefits, and briefly
      speculate on the possible effects of leukoreduction and blood storage on the need
      to reevaluate transfusion triggers. DESIGN: A review of the current literature
      was performed. RESULTS: Anemia is common in intensive care unit patients and is
      associated with increased mortality. Some 20-53% of intensive care unit patients
      will receive a blood transfusion during their stay, and these have also been
      associated with worse outcomes. Leukoreduction may limit some of the infectious
      and immunomodulatory risks associated with blood transfusion. CONCLUSIONS: Data
      on the risks and benefits of blood transfusion are conflicting, and with recent
      changes in blood transfusion practice, including the widespread introduction of
      leukoreduction, it is time to reevaluate our transfusion triggers.

PMID- 16617265
TI  - On conflicts of interest.

PMID- 16617266
TI  - Kafka's truth-seeking dogs.

PMID- 16617267
TI  - What to declare and why?

PMID- 16617268
TI  - He who pays the piper, calls the tune.....

PMID- 16617269
TI  - Why focus only on financial interests?

PMID- 16617270
TI  - A conflict-of-interest policy for epidemiology.

PMID- 16617271
TI  - Participation in population studies.

PMID- 16617272
TI  - Control recruitment in population-based case-control studies.

PMID- 16617273
TI  - The price is right.

PMID- 16617274
TI  - Instrumental variables: application and limitations.
AB  - To correct for confounding, the method of instrumental variables (IV) has been
      proposed. Its use in medical literature is still rather limited because of
      unfamiliarity or inapplicability. By introducing the method in a nontechnical
      way, we show that IV in a linear model is quite easy to understand and easy to
      apply once an appropriate instrumental variable has been identified. We also
      point out some limitations of the IV estimator when the instrumental variable is
      only weakly correlated with the exposure. The IV estimator will be imprecise
      (large standard error), biased when sample size is small, and biased in large
      samples when one of the assumptions is only slightly violated. For these reasons,
      it is advised to use an IV that is strongly correlated with exposure. However, we
      further show that under the assumptions required for the validity of the method,
      this correlation between IV and exposure is limited. Its maximum is low when
      confounding is strong, such as in case of confounding by indication. Finally, we
      show that in a study in which strong confounding is to be expected and an IV has
      been used that is moderately or strongly related to exposure, it is likely that
      the assumptions of IV are violated, resulting in a biased effect estimate. We
      conclude that instrumental variables can be useful in case of moderate
      confounding but are less useful when strong confounding exists, because strong
      instruments cannot be found and assumptions will be easily violated.

PMID- 16617275
TI  - Evaluating short-term drug effects using a physician-specific prescribing
      preference as an instrumental variable.
AB  - BACKGROUND: Postmarketing observational studies of the safety and effectiveness
      of prescription medications are critically important but fraught with
      methodological problems. The data sources available for such research often lack
      information on indications and other important confounders for the drug exposure
      under study. Instrumental variable methods have been proposed as a potential
      approach to control confounding by indication in nonexperimental studies of
      treatment effects; however, good instruments are hard to find. METHODS: We
      propose an instrument for use in pharmacoepidemiology that is based on a time
      varying estimate of the prescribing physician's preference for one drug relative
      to a competing therapy. The use of this instrument is illustrated in a study
      comparing the effect of exposure to COX-2 inhibitors with nonselective,
      nonsteroidal antiinflammatory medications on gastrointestinal complications.
      RESULTS: Using conventional multivariable regression adjusting for 17 potential
      confounders, we found no protective effect due to COX-2 use within 120 days from
      the initial exposure (risk difference = -0.06 per 100 patients; 95% confidence
      interval = -0.26 to 0.14). However, the proposed instrumental variable method
      attributed a protective effect to COX-2 exposure (-1.31 per 100 patients; -2.42
      to -0.20) compatible with randomized trial results (-0.65 per 100 patients; -1.08
      to -0.22). CONCLUSIONS: The instrumental variable method that we have proposed
      appears to have substantially reduced the bias due to unobserved confounding.
      However, more work needs to be done to understand the sensitivity of this
      approach to possible violations of the instrumental variable assumptions.

PMID- 16617276
TI  - Estimation of direct causal effects.
AB  - Many common problems in epidemiologic and clinical research involve estimating
      the effect of an exposure on an outcome while blocking the exposure's effect on
      an intermediate variable. Effects of this kind are termed direct effects.
      Estimation of direct effects is typically the goal of research aimed at
      understanding mechanistic pathways by which an exposure acts to cause or prevent
      disease, as well as in many other settings. Although multivariable regression is
      commonly used to estimate direct effects, this approach requires assumptions
      beyond those required for the estimation of total causal effects. In addition,
      when the exposure and intermediate variables interact to cause disease,
      multivariable regression estimates a particular type of direct effect-the effect
      of an exposure on an outcome when the intermediate is fixed at a specified level.
      Using the counterfactual framework, we distinguish this definition of a direct
      effect (controlled direct effect) from an alternative definition, in which the
      effect of the exposure on the intermediate is blocked, but the intermediate is
      otherwise allowed to vary as it would in the absence of exposure (natural direct
      effect). We illustrate the difference between controlled and natural direct
      effects using several examples. We present an estimation approach for natural
      direct effects that can be implemented using standard statistical software, and
      we review the assumptions underlying our approach (which are less restrictive
      than those proposed by previous authors).

PMID- 16617277
TI  - Toward guidelines for the ethical reanalysis and reinterpretation of another's
      research.
AB  - Reanalysis and reinterpretation occur when a person other than the original
      investigator obtains an epidemiologic data set and conducts analyses to evaluate
      the quality, reliability or validity of the dataset, methods, results or
      conclusions reported by the original investigator. We propose ethical guidelines
      with regard to the duty of original investigators to cooperate with competent
      impartial reanalysis and for the sponsors of reanalysis and reinterpretation and
      the epidemiologists who carry it out. The rights and interests of these parties
      and of the public interest need to be protected.

PMID- 16617278
TI  - Birth weight and blood pressure in spouses.

PMID- 16617279
TI  - Anthropometry and multiple myeloma.

PMID- 16617280
TI  - Sex distribution of newborns to mothers with systemic lupus erythematosus.

PMID- 16617281
TI  - Interactions with income.

PMID- 16617282
TI  - Ambient ozone and lung function.

PMID- 16617285
TI  - Botulism from home-canned bamboo shoots--Nan Province, Thailand, March 2006.
AB  - On March 15, 2006, multiple persons with symptoms of nausea, vomiting, abdominal
      pain, and dyspnea visited the emergency department at Baan Luang district
      hospital in Nan province, Thailand; one person required mechanical ventilation. A
      team from the Bureau of Epidemiology, Department of Disease Control, Thailand
      Ministry of Public Health (MOPH) initiated an investigation, in collaboration
      with the Surveillance and Rapid Response Team from Baan Luang district. This
      report summarizes the investigation conducted during March 15-26, which
      determined that the outbreak was caused by foodborne botulism from home-canned
      bamboo shoots and affected 163 rural villagers who shared a common meal. The last
      case was identified March 21; no further cases of foodborne botulism have been
      identified in the region.

PMID- 16617287
TI  - Multisite outbreak of norovirus associated with a franchise restaurant--Kent
      County, Michigan, May 2005.
AB  - The majority of cases of foodborne gastroenteritis in the United States are
      caused by noroviruses. This report summarizes an investigation by the Kent County
      Health Department (KCHD) in Michigan into three norovirus outbreaks and a cluster
      of community cases that were associated with a national submarine sandwich
      franchise restaurant during May 3-9, 2005. The investigation identified a
      potential source, a food handler who had returned to work within a few hours of
      having symptoms of gastrointestinal illness while he was still excreting
      norovirus in his stools. To prevent norovirus outbreaks, food service workers
      should be educated regarding norovirus transmission and control. In 2005, new
      guidelines for state health departments regarding norovirus containment were
      published by the Food and Drug Administration (FDA); guidelines for local health
      departments in Michigan were issued by the state's Department of Community Health
      and Department of Agriculture. The new guidelines for Michigan recommend that
      food service workers with suspected norovirus not return to work until they are
      asymptomatic for 48-72 hours.

PMID- 16617286
TI  - Preliminary FoodNet data on the incidence of infection with pathogens transmitted
      commonly through food--10 States, United States, 2005.
AB  - Foodborne illnesses are a substantial health burden in the United States. The
      Foodborne Diseases Active Surveillance Network (FoodNet) of CDC's Emerging
      Infections Program collects data from 10 U.S. states regarding diseases caused by
      enteric pathogens transmitted commonly through food. FoodNet quantifies and
      monitors the incidence of these infections by conducting active, population-based
      surveillance for laboratory-confirmed illness. This report describes preliminary
      surveillance data for 2005 and compares them with baseline data from the period
      1996-1998. Incidence of infections caused by Campylobacter, Listeria, Salmonella,
      Shiga toxin-producing Escherichia coli O157 (STEC O157), Shigella, and Yersinia
      has declined, and Campylobacter and Listeria incidence are approaching levels
      targeted by national health objectives. However, most of those declines occurred
      before 2005, and Vibrio infections have increased, indicating that further
      measures are needed to prevent foodborne illness.

PMID- 16617288
TI  - Survey of lymphocytic choriomeningitis virus diagnosis and testing--Connecticut,
      2005.
AB  - Lymphocytic choriomeningitis virus (LCMV) is a rodent borne virus that can be
      transmitted to humans through exposure to rodent urine, feces, saliva, or blood.
      LCMV infection is often asymptomatic or mild but can cause aseptic meningitis,
      encephalitis, life-threatening infections in immunosuppressed persons, and severe
      congenital defects . In May 2005, LCMV was implicated in the deaths of three
      organ transplant recipients who had received organs from a common donor who had
      likely been infected from a pet rodent. In August 2005, the Connecticut
      Department of Public Health conducted surveys of hospital laboratories and
      infectious disease (ID) physicians in Connecticut to determine recent incidence
      of confirmed LCMV infection, the level of awareness of LCMV, and the frequency of
      LCMV testing. This report summarizes the results of those surveys, which indicate
      that awareness of LCMV is high among ID physicians; however, testing for LCMV is
      infrequent, and ID physicians might not be aware of the need to consider LCMV
      among the most susceptible populations even when a history of rodent contact is
      not initially evident. In part because of these findings, LCMV infection is now a
      physician- and laboratory-reportable disease in Connecticut. More systematic
      efforts are needed to determine the frequency of LCMV infection and to monitor
      for pet rodent infection.

PMID- 16617289
TI  - Fusarium keratitis--multiple states, 2006.
AB  - On March 8, 2006, CDC received a report from an ophthalmologist in New Jersey
      regarding three patients with contact lens--associated Fusarium keratitis during
      the preceding 3 months. Initial contact with several corneal disease specialty
      centers in the United States revealed that other centers also have seen recent
      increases in Fusarium keratitis. This report summarizes the public health
      response to date in the United States and provides important prevention messages
      for contact lens users.

PMID- 16617290
TI  - Exposure to mumps during air travel--United States, April 2006.
AB  - The state of Iowa has been experiencing a large mumps outbreak that began in
      December 2005. As of April 10, 2006, a total of 515 possible mumps cases have
      been reported to the Iowa Department of Public Health (IDPH) during 2006. This
      outbreak has spread across Iowa, and mumps activity, possibly linked to the Iowa
      outbreak, is under investigation in six neighboring states, including Illinois (n
      = four), Kansas (n = 33), Minnesota (n = one), Missouri (n = four), Nebraska (n =
      43), and Wisconsin (n = four) (CDC, unpublished data, April 10, 2006). The
      reasons for this outbreak are under investigation.

PMID- 16617291
TI  - Update: influenza activity--United States, March 26-April 1, 2006.
AB  - During March 26-April 1, 2006, the number of states reporting widespread
      influenza activity decreased to 13. Fourteen states reported regional activity,
      12 reported local activity, 10 reported sporadic activity, and one reported no
      activity.

PMID- 16617292
TI  - Recommendations to improve preconception health and health care--United States. A
      report of the CDC/ATSDR Preconception Care Work Group and the Select Panel on
      Preconception Care.
AB  - This report provides recommendations to improve both preconception health and
      care. The goal of these recommendations is to improve the health of women and
      couples, before conception of a first or subsequent pregnancy. Since the early
      1990s, guidelines have recommended preconception care, and reviews of previous
      studies have assessed the evidence for interventions and documented the evidence
      for specific interventions. CDC has developed these recommendations based on a
      review of published research and the opinions of specialists from the CDC/ATSDR
      Preconception Care Work Group and the Select Panel on Preconception Care. The 10
      recommendations in this report are based on preconception health care for the
      U.S. population and are aimed at achieving four goals to 1) improve the knowledge
      and attitudes and behaviors of men and women related to preconception health; 2)
      assure that all women of childbearing age in the United States receive
      preconception care services (i.e., evidence-based risk screening, health
      promotion, and interventions) that will enable them to enter pregnancy in optimal
      health; 3) reduce risks indicated by a previous adverse pregnancy outcome through
      interventions during the interconception period, which can prevent or minimize
      health problems for a mother and her future children; and 4) reduce the
      disparities in adverse pregnancy outcomes. The recommendations focus on changes
      in consumer knowledge, clinical practice, public health programs, health-care
      financing, and data and research activities. Each recommendation is accompanied
      by a series of specific action steps and, when implemented, can yield results
      within 2-5 years. Based on implementation of the recommendations, improvements in
      access to care, continuity of care, risk screening, appropriate delivery of
      interventions, and changes in health behaviors of men and women of childbearing
      age are expected to occur. The implementation of these recommendations will help
      achieve Healthy People 2010 objectives. The recommendations and action steps are
      a strategic plan that can be used by persons, communities, public health and
      clinical providers, and governments to improve the health of women, their
      children, and their families. Improving preconception health among the
      approximately 62 million women of childbearing age will require multistrategic,
      action-oriented initiatives.

PMID- 16617293
TI  - Computer modeling of secondary fiber development and growth: I. Nonprimate
      lenses.
AB  - PURPOSE: The purpose of this study was to use qualitative and quantitative
      structural data from nonprimate lenses with branched (Y and line) sutures to
      generate computer models (animations) of secondary fiber development and suture
      formation. METHODS: A minimum of 12-18 adult lenses/species (mice, cows, frogs,
      and rabbits) were used in this study. Lenses were analyzed by light (LM),
      transmission (TEM), and scanning electron microscopy (SEM). Fiber width,
      thickness, and length were ascertained from micrographs and by using formulations
      to calculate distances between degrees of latitude and longitude on asymmetrical
      oblate spheroids. This information was then used to create scale computer
      assisted drawings (CADs) of fibers at different stages of their development. The
      CADs were then placed on a timeline and animated to produce dynamic
      representations of secondary fiber development and growth. RESULTS: Animating
      secondary fiber development and suture formation with the inclusion of
      quantifiable differences in fiber dimensions at progressive stages of their
      differentiation revealed the following: first, there is the presumption that
      fibers migrate, rotate, and elongate until they reach their sutural destinations
      is not likely to be correct. When developing fibers reach approximately 60-65% of
      their eventual total length, their migration and rotation is complete. The
      remaining fiber elongation (the production of end segments) occurs without either
      concomitant cellular migration or rotation. Second, it is presumed that suture
      branches originate peripherally and are then constructed sequentially until all
      of the branches come to confluence at the poles is also not likely to be correct.
      While suture branches do originate peripherally, if the rate of elongation is
      constant in the anterior and posterior directions (intrafiber elongation speed)
      and between developing fibers within a forming growth shell (interfiber
      elongation speed), then only a part of their construction proceeds sequentially
      toward the poles. A second suture branch origin will be established at the poles
      resulting in a short distal portion of suture branches being formed sequentially
      in the reverse direction. Suture formation will conclude when a long proximal and
      a short distal portion of branches come to confluence within unequal anterior and
      posterior polar cap regions. This segmented suture formation scheme will be more
      pronounced in line suture lenses than in Y suture lenses. Third, because lenses
      with branched sutures have growth shells consisting of fibers of unequal length,
      fiber maturation is likely to be initiated in these lenses before a growth shell
      as well as suture formation is completed and would proceed in distinct patterns
      over a period of time. This is in marked contrast to avian lens fiber maturation
      which does not begin until growth shell and suture (branchless umbilical)
      formation is completed and then occurs rapidly and essentially simultaneously
      across the entire growth shell. CONCLUSIONS: Animations of secondary fiber
      development and suture formation based on quantitative analysis of electron
      micrographs reveals important novel aspects of these processes that have not been
      apparent from the results of previous mechanistic studies. The more complex
      schemes of fiber differentiation and suture formation presented herein are
      consistent with the notion that lens function (dynamic focusing) is
      interdependent on lens structure and physiology. The animations confirm that
      while all vertebrate lenses have a similar structure, differences in the level of
      their structural complexity established early in development and maintained
      throughout life can account for the varying amount of optical quality known to
      exist between species.

PMID- 16617295
TI  - Structure of asteroid bodies in the vitreous of galactose-fed dogs.
AB  - PURPOSE: Asteroid hyalosis is a condition in which white spherical particles
      (asteroid bodies) are suspended in the vitreous, usually in the dependent part of
      the vitreous. These particles seldom cause serious visual symptoms; however,
      their presence can be a source of irritation. It has been suggested, but not
      confirmed, that asteroid hyalosis may be associated with systemic diseases such
      as diabetes, hyperlipidemia, or hypertension. Studies indicate that these
      particles are composed of lipid material and calcium; however, the specific
      composition and structure of asteroid bodies remains unknown. We have observed
      that asteroid hyalosis occurs in galactose-fed dogs, and this represents the
      first animal model which consistently forms this vitreal condition. The purpose
      of this study was to identify the main structural component of the asteroid
      bodies present in the vitreous of these dogs. METHODS: Vitreous humor containing
      asteroid bodies was collected and frozen from long-term galactose-fed beagles and
      from age-matched normal controls where asteroid bodies were absent. A portion of
      the frozen vitreous was sent out for elemental analysis. Thawed vitreous samples
      were sonicated with HPLC grade water and the aqueous layer was extracted three
      times with chloroform and then three times with n-butanol. The three organic
      layers from each extraction were combined and the solvents removed in vacuo. The
      residue from each extraction was re-dissolved in methanol and analyzed by
      electrospray ionization mass spectrometry (ESI-MS). RESULTS: Vitreous-containing
      asteroid bodies had significantly higher levels of calcium and phosphorus.
      Negative mode ESI-MS analysis of the n-butanol extracts from vitreous samples
      with and without asteroid bodies were similar with both containing a predominant
      peak with a mass to charge ratio (m/z) of 538.4. However, similar analyses of the
      chloroform extracts indicated that three peaks with m/z values of 547.1, 690.5,
      and 1430.6 were present only in vitreous samples containing asteroid bodies.
      Subtraction analysis indicated that the m/z of 690.5 peak corresponded to the
      main component present. This peak was identified and confirmed to be the
      quasimolecular ion of 1,2-dipalmitoyl-glycero-3-phosphoethanolamine (DPPE).
      CONCLUSIONS: Based on the current belief that asteroid bodies are composed of
      lipid-calcium complexes, we propose that the main component of asteroid hyalosis
      in the galactose-fed dog is a quasimolecular ion of DPPE in which two molecules
      of DPPE are complexed through their phosphates groups with calcium.

PMID- 16617294
TI  - Estradiol attenuates mitochondrial depolarization in polyol-stressed lens
      epithelial cells.
AB  - PURPOSE: This study examined the state of mitochondrial physiology subsequent to
      exposing lens epithelium to high ambient galactose (Gal), which upon conversion
      to galactitol (GalOH) and resultant intracellular accumulation thereof, leads to
      profound destabilization of mitochondrial membrane potential (Deltapsim).
      Further, we determined whether the aldose reductase (AR) inhibitor, Sorbinil, or
      estrogen (17beta-E2, and its isomer, 17alpha-E2, which exhibits marginal binding
      affinity for estrogen receptor), administered prior to and concomitant with Gal
      exposure might prevent or delay mitochondrial membrane depolarization. METHODS:
      Secondary cultures of bovine lens epithelial cells (BLECs), as well as a virally
      transformed human lens epithelial cell line (HLE-B3), were maintained in 40 mM
      galactose (Gal) for up to seven days in the presence and absence of Sorbinil,
      17beta-E2 or 17alpha-E2. Endogenous accumulation of reactive oxygen species (ROS)
      was assessed by loading cells with H2DCF-DA, which upon oxidation in the presence
      of ROS transitions to the fluorescent compound, DCF. To assess Deltapsim,
      confocal microscopy was employed in conjunction with the potentiometric dye, JC
      1. Intracellular polyol content was determined by gas chromatography. Cells were
      monitored for apoptosis and necrosis as determined by annexin V-propidium iodide
      staining and visualized by confocal fluorescence microscopy. RESULTS: BLECs, more
      so than HLE-B3 cells, accumulate high intracellular levels of GalOH upon exposure
      to high ambient Gal. BLECs were significantly depolarized while HLE-B3 cells
      showed little depolarization over the same course of Gal exposure. The addition
      of either 17alpha-E2 or 17beta-E2 to BLECs, over a dose range of 0.01 microM to
      1.0 microM, prevented mitochondrial membrane depolarization as did the addition
      of 0.1 mM Sorbinil. The polyol content in BLECs after 3 days of exposure to Gal
      was 282 nmol/mg protein. Co-addition of Sorbinil during the 3-day exposure period
      prevented any significant accumulation of GalOH. Co-administration of either
      isoform of estrogen did not block GalOH synthesis and the level of attained
      intracellular accumulation was similar to that of Gal alone. The observed
      accumulation of ROS from HLE-B3 cells subsequent to 3 days of Gal exposure was
      negligible and consistent with that of control cells maintained in physiological
      medium. Intracellular accumulation of ROS with 3-day, Gal-maintained BLECs,
      exhibited a marginal but statistically significant increase over control cells
      maintained in physiological medium (5.5 mM glucose) and similar levels of ROS
      were generated irrespective of the presence of estrogen with Gal. Bolus addition
      of 100 microM hydrogen peroxide to 3-day, Gal plus Sorbinil-maintained BLECs
      failed to induce a change in mitochondrial membrane potential. Evidence of
      apoptosis or necrosis was negligible through 7 days of sustained exposure to high
      ambient Gal. CONCLUSIONS: Polyol accumulation promotes mitochondrial membrane
      depolarization and the decrease in Deltapsim is prevented by prior addition and
      co-administration of Sorbinil or estrogen with Gal. Unlike Sorbinil, estrogens'
      mode of action is not via the inhibition of aldose reductase activity. The data
      supports the theory that with Gal plus estradiol-treated cells, at a given
      intracellular polyol load, a larger portion of the mitochondrial population
      retains Deltapsim, and hence continues to function relative to Gal-treated cells.
      Results with 17alpha-E2 indicate that maintaining Deltapsim, in the face of
      chronic polyol accumulation, is likely to be mediated via a nuclear estrogen
      receptor-independent mechanism. The failure of supraphysiological levels of
      hydrogen peroxide added to Gal plus Sorbinil-maintained BLECs to depolarize
      mitochondria indicates that polyol accumulation, not ROS generation, is the
      causative factor responsible for the loss of mitochondrial membrane potential.

PMID- 16617296
TI  - CB1 cannabinoid receptor-mediated changes of trabecular meshwork cellular
      properties.
AB  - PURPOSE: To evaluate the roles of CB1 cannabinoid receptors in cellular functions
      of trabecular meshwork (TM) cells, including cell migration, adhesion, morphology
      and cytoskeleton changes. METHODS: Noladin ether, a selective CB1 receptor
      agonist, and SR141716A, a selective CB1 receptor antagonist, were used to
      characterize the cellular functions of cultured porcine TM cells. Fluorescence
      assisted transmigration invasion and motility assays (FATIMA) were conducted to
      study TM cell migration using soluble fibronectin as a chemoattractant. Wound
      healing assays were used to further study TM cell migration. Standard cell
      adhesion assays of TM cells were performed on fibronectin-coated plates. In
      morphological studies, Alexafluor 488-labeled phalloidin staining was used to
      examine actin filaments, and immunocytochemistry using anti-paxillin antibodies
      was used to detect focal adhesions. RESULTS: In cell migration assays, CB1
      agonist noladin ether at nanomolar ranges led to a concentration-dependent
      inhibition of migration of TM cells toward soluble fibronectin. CB1 antagonist
      SR141716A antagonized noladin ether-induced inhibition of migration of TM cells.
      In addition, noladin ether caused a delay in wound healing of confluent
      trabecular meshwork monolayers and this effect of noladin ether was antagonized
      by SR141716A. In cell adhesion assays, noladin ether treatment led to a moderate,
      but significant decrease of adhesion of TM cells to fibronectin-coated surface.
      This effect of noladin ether was concentration-dependent, and was antagonized by
      SR141716A. In morphological studies, noladin ether treatment caused rounding of
      TM cells in contrast to well-spread control TM cells. In addition, there was a
      reduction and fragmentation of actin stress fibers stained with Alexafluor 488
      labeled phalloidin and a decrease of focal adhesions detected with an anti
      paxillin antibody. CONCLUSIONS: Noladin ether modulates the migration, adhesion,
      morphology, and actin cytoskeleton of TM cells. These effects of noladin ether
      are mediated through TM cell CB1 cannabinoid receptors.

PMID- 16617297
TI  - Does recombinant adeno-associated virus-vectored proximal region of mouse
      rhodopsin promoter support only rod-type specific expression in vivo?
AB  - PURPOSE: We have previously found that the -385 to +86 portion of the mouse rod
      opsin promoter (mOP500) can limit recombinant adeno-associated virus (rAAV)
      mediated transgene expression to photoreceptor cells when delivered subretinally.
      However, the photoreceptor (PR) subtype-specificity of expression remains
      unclear. Here, we evaluated whether the presence of certain cis-elements in this
      proximal promoter, such as the rod-specific, neural retina leucine zipper protein
      (NRL) response element (NRE), can render it a driver of rod-specific expression.
      METHODS: Subretinal injections of a serotype 5 rAAV vector carrying the green
      fluorescent protein (GFP) cDNA, driven by mOP500, were administered to male
      Sprague-Dawley rats at postnatal day (P) 40-48. Two weeks to eight months later,
      the distribution of GFP-expressing cells in the retina was characterized by GFP-,
      cone-specific alpha-transducin-immuno-, and peanut agglutinin-lectin
      histochemistry and by morphological criteria. The same viral suspension was also
      injected sub-retinally into rhodopsin-knockout rho (-/-) mice either at P18 or
      P78, and retinas were analyzed by immunohistochemistry and PNA lectin
      histochemistry two weeks later. RESULTS: GFP reactivity was found exclusively in
      the outer nuclear layer (ONL) of rat retinas two weeks after treatment, with
      abundant reporter gene expression observed in both rods and cones. GFP-positive
      cones, defined by their typical morphology and the co-linearity of PNA-lectin
      labeling with GFP-immunoreactivity, were found in all regions of the transduced
      retinas. GFP-positive cones constituted up to 6% of the total GFP-positive
      photoreceptors. By eight months post-injection, a low level of GFP-reactivity was
      additionally observed in the inner nuclear layer (INL) and ganglion cell layer.
      Photoreceptor-specific GFP expression was also seen in the rho (-/-) mice at both
      ages tested. In pups injected at P18, costaining with PNA-lectin revealed that up
      to 15% of the GFP-positive photoreceptors were cones. Despite only a single row
      of photoreceptors remaining in these knockout mice by P90, numerous GFP-positive
      cones were still present. CONCLUSIONS: Subretinal delivery of rAAV5 harboring a
      reporter gene driven by mOP500 results in passenger gene expression in both rod
      and cones, indicating that this promoter is photoreceptor-specific but not rod
      specific. The lack of photoreceptor subtype-specificity suggests that although
      cones do not express the NRL and NR2E3 trans-factors considered necessary for
      activation of mOP500, other general transcription factors in cones may
      compensate.

PMID- 16617298
TI  - Role of VLA-4 in the development of allergic conjunctivitis in mice.
AB  - PURPOSE: The severity of allergic conjunctivitis (AC) correlates with the degree
      of eosinophil infiltration into the conjunctiva, which is believed to be mediated
      by chemokines and adhesion molecules. The adhesion molecule very late antigen
      (VLA)-4 and its ligand, vascular cell adhesion molecule (VCAM)-1, are known to
      play important roles in eosinophil infiltration. However, the expression and
      function of VLA-4 in AC have not been investigated in detail. We sought to
      characterize VLA-4-expressing cells in the conjunctivas of mice that are
      developing experimental AC (EC) and to determine whether the interaction between
      VLA-4 and VCAM-1 is needed for the infiltration of eosinophils into the
      conjunctiva in AC. METHODS: EC was induced in Balb/c mice by active immunization
      with ragweed (RW) or adoptive transfer of RW-primed splenocytes, followed by RW
      challenge. Twenty-four hours after RW challenge, the conjunctivas were harvested.
      The conjunctivas from naive mice or mice developing EC were evaluated for VLA-4
      and VCAM-1 expression by immunohistochemistry and immunofluorescent analyses. To
      investigate whether the interaction between VLA-4 and VCAM-1 is needed for the
      genesis of AC, mice developing EC were treated with anti-VLA-4 or anti-VCAM-1
      antibodies two h before and after RW challenge. As a control, EC-developing mice
      were treated with normal rat IgG. Twenty-four hours after RW challenge, the
      conjunctivas were harvested for histological analysis. RESULTS: Upon induction of
      EC, VLA-4-expressing cells infiltrated the conjunctiva but the constitutive VCAM
      1 expression around conjunctival vessels was not augmented. Immunofluorescent
      analyses demonstrated that most of the T cells infiltrating the conjunctiva
      expressed VLA-4 but only half of the infiltrating eosinophils expressed it.
      Treatment with both anti-VLA-4 and anti-VCAM-1 antibodies significantly
      suppressed the infiltration of eosinophils into the conjunctiva that was induced
      by either active immunization or splenocyte transfer. CONCLUSIONS: These results
      confirm that VLA-4-expressing cells infiltrate the conjunctiva and that the
      interaction between VLA-4 and VCAM-1 is needed for the development of EC.

PMID- 16617299
TI  - PAX6 gene intragenic deletions in Mexican patients with congenital aniridia.
AB  - PURPOSE: To present the results of molecular analysis of the PAX6 gene in a group
      of patients with congenital aniridia from Mexican mestizo origin, a previously
      unstudied ethnic group. METHODS: Five unrelated affected probands, four
      pertaining to familial cases and one sporadic, were studied at the Institute of
      Ophthalmology "Conde de Valenciana" in Mexico City. All patients underwent full
      ophthalmologic examination as well as PAX6 analysis in genomic DNA using a
      combination of exon-by-exon PCR amplification, direct sequencing, and allele
      specific cloning/sequencing. Available affected relatives were also investigated.
      RESULTS: Three novel intragenic deletions were identified: a 15 bp deletion in
      exon nine that removes the last two codons of the exon and the first nine bases
      of intron 10, including the conserved GT splicing donor signal; a 14 bp deletion
      in exon six that introduces a premature stop signal 15 codons downstream and a
      four bp deletion in exon seven, which introduces a stop signal 22 codons
      downstream, in three unrelated probands. Although unrelated, these three latter
      cases came from the same geographical area, strongly suggesting a founder
      mutation effect as the source of the anomaly. CONCLUSIONS: Our study provides the
      first molecular analysis of the PAX6 gene in Mexican subjects with congenital
      aniridia, identifies three novel intragenic PAX6 deletions, and suggests the
      occurrence of a PAX6 founder mutation effect in this population. Our results also
      confirm the current notion that PAX6 truncating mutations are overwhelmingly
      associated with aniridia regardless of their location in the gene.

PMID- 16617300
TI  - Tumor-specific therapeutic effect induced by an oncolytic adenoviral vector
      containing heat shock protein 70 and prodrug activation genes.
AB  - We constructed a melanoma-specific oncolytic adenoviral vector
      Ad.MCDIRESE1.71Hsp3, in which the cytosine deaminase and adenoviral E1A genes
      linked by the IRES sequence were under the control of a mouse tyrosinase
      enhancer/promoter transcriptional element in the E1 region of the vector. We also
      inserted the human heat shock protein 70 (Hsp70) gene driven by the
      cytomegalovirus promoter into the E3 region of this vector. The RGD-4C peptide
      was inserted into the HI loop of the fiber knob domain of the Ad.MCDIRESE1.71Hsp3
      vector to increase the transduction efficiency of this vector to tumor cells. The
      Ad.MCDIRESE1.71Hsp3 vector replicates specifically in melanoma cells, and it has
      a melanoma-specific cytotoxic effect in the presence of 5-fluorocytosine in vitro
      and in vivo. Moreover, the in vivo killing of tumor cells associated with the
      overexpression of Hsp70 generated by the intratumoral injection of the
      Ad.MCDIRESE1.71Hsp3 vector into established subcutaneous tumors can lead to the
      suppression of tumor growth and potent melanoma-specific systemic immune
      responses.

PMID- 16617301
TI  - Gene therapy for long-term restoration of circulating thymulin in thymectomized
      mice and rats.
AB  - Thymulin is a thymic peptide possessing hypophysiotropic activity and
      antiinflammatory effects in the brain. We constructed a synthetic DNA sequence
      encoding met-FTS, a biologically active analog of thymulin, and subsequently
      cloned it into different expression vectors. A sequence optimized for expression
      of met-FTS in rodents, 5'-ATGCAGGCCAAGTCGCAGGGGGGGTCGAACTAGTAG-3', was cloned in
      the mammalian expression vectors pCDNA3.1(+) and phMGFP (which expresses the
      Monster Green Fluorescent Protein), thus obtaining pcDNA3.1-metFTS and p-metFTS
      hMGFP, which express met-FTS and the fluorescent fusion protein metFTS-hMGFP,
      respectively. The synthetic sequence was also used to construct the adenoviral
      vector RAd-metFTS, which expresses met-FTS. Transfection of HEK293 and BHK cells
      with pcDNA3.1-metFTS (experimental groups) or pcDNA3.1 (control), led to high
      levels of thymulin bioactivity (>600 versus <0.1 pg/ml in experimental and
      control supernatants, respectively). Transfection of HEK293 and BHK cells with
      pmetFTS-hMGFP revealed a cytoplasmic and nuclear distribution of the fluorescent
      fusion protein. A single intramuscular (i.m.) injection (10(7) plaque forming
      units (PFU)/mouse or 10(8) PFU/rat) of RAd-metFTS in thymectomized animals
      (nondetectable serum thymulin) restored serum thymulin levels for at least 110
      and 130 days post-injection in mice and rats, respectively. We conclude that RAd
      metFTS constitutes a suitable biotechnological tool for the implementation of
      thymulin gene therapy in animal models of chronic brain inflammation.

PMID- 16617302
TI  - Increased VEGF levels induced by anti-VEGF treatment are independent of tumor
      burden in colorectal carcinomas in mice.
AB  - Inhibition of vascular endothelial growth factor (VEGF) by gene transfer
      techniques was effectively applied to control experimental tumor growth, whereas
      effects on systemic VEGF levels had not been investigated. Therefore, we
      evaluated the effect of VEGF inhibition by adenoviral-mediated gene delivery of a
      dominant-negative soluble fragment of FLK-1 (sFlk-1) on systemic VEGF levels,
      organ-specific VEGF-RNA expression and antitumor efficacy in a murine colorectal
      cancer (CRC) tumor model. Vector function of AdsFlk-1 was shown by Western blot
      analysis and transgene expression was documented over a time period of 42 days in
      the serum of treated mice. Although cell supernatant of CT26 cells contained
      considerable levels of VEGF, systemic VEGF levels in the serum of tumor-bearing
      mice remained unaffected. Interestingly, mice that were systemically treated with
      AdsFlk-1 showed a strong upraise of circulating VEGF, whereas VEGF remained at
      background levels in the control. Vascular endothelial growth factor was
      increased not only in tumor bearing but also in healthy, tumor-free mice.
      Vascular endothelial growth factor determination in liver tissue homogenates
      showed a 16.5-fold upraise in AdsFlk-1-treated animals as compared to the AdLacZ
      control. Consecutively, systemic small interfering RNA injection targeted against
      VEGF reverted elevated VEGF levels almost back to normal levels. In spite of
      elevated VEGF levels, AdsFlk-1 administration showed significant antitumor
      effects in a subcutaneous metastatic CRC tumor model. There was no significant
      correlation between antitumour treatment response and VEGF levels in this model.
      Collectively, we conclude that the systemic administration of AdsFlk-1 had
      significant inhibitory effects on metastatic CRC tumor growth in spite of
      elevated systemic VEGF levels and that VEGF serum concentrations did not
      correlate to tumor burden and antitumor treatment response in this model.

PMID- 16617303
TI  - Sequence variations in the 5' upstream regions of the FBN1 gene associated with
      Marfan syndrome.
AB  - Marfan syndrome (MFS; OMIM#154700) is a connective tissue disorder characterized
      by manifestations in the ocular, skeletal and cardiovascular systems. MFS is
      caused by mutation in the fibrillin-1 gene (FBN1; OMIM#134797) and more than 550
      mutations have been identified so far. FBN1 is approximately 230 kb in size and
      contains three evolutionarily conserved alternatively spliced exons B, A and C at
      the 5'end. In a first systematic attempt to associate sequence variations in the
      FBN1 5' alternatively spliced exons with MFS, we investigated 41 individuals
      fulfilling the diagnostic criteria of Ghent nosology or with features of MFS
      including at least one major criterion or involvement of two organ systems but
      not fulfilling a strict interpretation of the Ghent nosology, and known to be
      negative for mutations in the FBN1 exons 1-65 as well as the TGFBR2 and TGFBR1
      coding regions. We identified five novel and one previously reported variants in
      the six unrelated probands and provide preliminary evidence for their role in
      pathogenesis.

PMID- 16617304
TI  - Parental and chromosomal origins of microdeletion and duplication syndromes
      involving 7q11.23, 15q11-q13 and 22q11.
AB  - Non-allelic homologous recombination between chromosome-specific LCRs is the most
      common mechanism leading to recurrent microdeletions and duplications. To look
      for locus-specific differences, we have used microsatellites to determine the
      parental and chromosomal origins of a large series of patients with de novo
      deletions of chromosome 7q11.23 (Williams syndrome), 15q11-q13 (Angelman
      syndrome, Prader-Willi syndrome) and 22q11 (Di George syndrome) and duplications
      of 15q11-q13. Overall the majority of rearrangements were interchromosomal, so
      arising from unequal meiotic exchange, and there were approximately equal numbers
      of maternal and paternal deletions. Duplications and deletions of 15q11-q13
      appear to be reciprocal products that arise by the same mechanisms. The
      proportion arising from interchromosomal exchanges varied among deletions with
      22q11 the highest and 15q11-q13 the lowest. However, parental and chromosomal
      origins were not always independent. For 15q11-q13, maternal deletions tended to
      be interchromosomal while paternal deletions tended to be intrachromosomal; for
      22q11 there was a possible excess of maternal cases among intrachromosomal
      deletions. Several factors are likely to be involved in the formation of
      recurrent rearrangements and the relative importance of these appear to be locus
      specific.

PMID- 16617305
TI  - Differences in methylation patterns in the methylation boundary region of IDS
      gene in Hunter syndrome patients: implications for CpG hot spot mutations.
AB  - Hunter syndrome, an X-linked disorder, results from deficiency of iduronate-2
      sulfatase (IDS). Around 40% of independent point mutations at IDS were found at
      CpG sites as transitional events. The 15 CpG sites in the coding sequences of
      exons 1 and 2, which are normally hypomethylated, account for very few of
      transitional mutations. By contrast, the CpG sites in the coding sequences of
      exon 3, though also normally hypomethylated, account for much higher fraction of
      transitional mutations. To better understand relationship between methylation
      status and CpG transitional mutations in this region, the methylation patterns of
      11 Hunter patients with transitional mutations at CpG sites were investigated
      using bisulfite genomic sequencing. The patient cohort mutation spectrum is
      composed of one mutation in exon 1 (one patient) and three different mutations in
      exon 3 (10 patients). We confirmed that in normal males, cytosines at the CpG
      sites from the promoter region to a portion of intron 3 were hypomethylated.
      However, specific CpG sites in this area were more highly methylated in patients.
      The patients with p.R8X (exon 1), p.P86L (exon 3), and p.R88H (exon 3) mutations
      had a hypermethylated condition in exon 2 to intron 3 but retained
      hypomethylation in exon 1. The same trend was found in four patients with p.A85T
      (exon 3), although the degree of hypermethylation was less. These findings
      suggest methylation patterns in the beginning of IDS genomic region are
      polymorphic in humans and that hypermethylation in this region in some
      individuals predisposes them to CpG mutations resulting in Hunter syndrome.

PMID- 16617306
TI  - Blood pressure measurement in atrial fibrillation: goodbye mercury?

PMID- 16617307
TI  - Blood pressure control in the setting of diabetes mellitus: new targets, new hope
      for improvement?

PMID- 16617308
TI  - The influence of socioeconomic status on blood pressure of Indonesian prepubertal
      children.

PMID- 16617309
TI  - Decreased pituitary response to insulin-induced hypoglycaemia in young lean male
      patients with essential hypertension.
AB  - Essential hypertension is associated with changes in central catecholaminergic
      pathways which might also be reflected in the pituitary response to stress
      stimuli. The aim of this study was to determine whether the response of pituitary
      hormones, cortisol, plasma renin activity, aldosterone and catecholamines to
      insulin-induced hypoglycaemia is changed in hypertension. We studied 22 young
      lean male patients with newly diagnosed untreated essential hypertension and 19
      healthy normotensive, age- and body mass index (BMI)-matched controls. All
      subjects underwent an insulin tolerance test (0.1 IU insulin/kg body weight
      intravenously) with blood sampling before and 15, 30, 45, 60 and 90 min after
      insulin administration. Increased baseline levels of norepinephrine (P<0.05),
      increased response of norepinephrine (P<0.001) and decreased response of growth
      hormone (P<0.001), prolactin (P<0.001), adrenocorticotropic hormone (P<0.05) and
      cortisol (P<0.001) were found in hypertensive patients when compared to
      normotensive controls. Increased norepinephrine levels and a decreased pituitary
      response to metabolic stress stimuli may represent another manifestation of
      chronically increased sympathetic tone in early hypertension.

PMID- 16617310
TI  - Optimal use and interpretation of the aldosterone renin ratio to detect
      aldosterone excess in hypertension.
AB  - With the introduction of the aldosterone/renin ratio as a screening test, the
      detection rate of primary aldosteronism has increased considerably. Nevertheless,
      no consensus has so far been reached regarding the cutoff points, operating
      characteristics or indeed even the reference values for reporting the
      aldosterone/renin ratio using plasma active renin (ng/l or mU/l) measured by
      immunoradiometric assay. We review the characteristics of this ratio in normal
      individuals, essential hypertension and primary hyperaldosteronism in an attempt
      to reach an agreement regarding its optimum use and interpretation - both using
      the renin activity or concentration. It seems that the optimal cutoff for
      patients with primary aldosteronism is above 30 ng/dl per mug/l/h or 800 pmol/l
      per mug/l/h or 130 pmol/ng or 80 pmol/mU. We explore enhancing measures such as
      captopril loading or use with a plasma aldosterone cutoff as well as pitfalls
      with the test such as confounding medications or the need for confirmatory
      testing. For the latter, demonstration of autonomous aldosterone production via
      salt loading is widely used, but may not be most advantageous and may even be
      contraindicated in patients with severe hypertension. The renin stimulation test
      may be an alternative being safe, well tolerated, and cost effective.

PMID- 16617311
TI  - Birth weight, puberty, and systolic blood pressure in children and adolescents: a
      longitudinal analysis.
AB  - We examined the association between birth weight and systolic blood pressure
      (SBP) from pre-puberty to late puberty in a cohort of American children. Ninety
      eight children aged 4-12 years at baseline were followed annually for 2-6 years
      with at least two Tanner stages. Annual measures included SBP, age, gender, race,
      birth weight, Tanner stage, and body composition using dual-energy X-ray
      absorptiometry and computed tomography. Birth weight was inversely correlated
      with SBP in pre-pubertal children (r=-0.23, P<0.05), especially in white
      children. SBP persisted at a higher level from pre-puberty through late puberty
      among children with low birth weight (<2500 g). However, SBP significantly
      increased from pre-puberty to early or late puberty among children with high
      birth weight (>or=4000 g). After adjusting for visceral fat, one unit change of
      birth weight category was associated with a 2.6 mm Hg reduction in SBP (P<0.05),
      but this association was attenuated as puberty progressed. The changes in SBP
      across puberty followed different trajectories in children with low vs high birth
      weight. Attenuation in the association between birth weight and SBP from pre
      puberty to late puberty may be influenced by sexual maturation.

PMID- 16617312
TI  - Can aneroid sphygmomanometers be used at altitude?
AB  - Mercury-independent devices are increasingly being used in clinical practice as
      mercury will soon be removed from clinical use as a result of environmental,
      health and safety concerns. The aim of this study was to evaluate the accuracy of
      a portable aneroid device in an adult population at high altitude by following
      the part of the protocol of the British Hypertension Society regarding comparison
      between device and observer. We examined 10 subjects in Cerro de Pasco, Peru,
      which is situated 4370 m above sea level. The aneroid device was initially
      calibrated at both high altitude and at sea level to ensure optimal function.
      Validation of the device was undertaken at high altitude by connecting it in
      parallel to two mercury sphygmomanometers. Eleven sequential same-arm
      measurements were taken from each subject by two trained observers, alternating
      between mercury sphygmomanometry and the aneroid device. Simultaneous mercury
      readings were also recorded for additional analysis. During calibration, all 60
      comparisons between the aneroid and mercury sphygmomanometers were within 3 mm Hg
      both at sea level and at high altitude. At validation, the device achieved an A
      grade for both systolic and diastolic pressures and also fulfilled the
      requirements of the Association for the Advancement of Medical Instrumentation.
      The mean and standard deviation for systolic and diastolic pressures,
      respectively, were -1.32 (4.3) mm Hg and 3.7 (4.7) mm Hg in sequential analysis
      and -0.7 (2.6) mm Hg and -3.3 (2.7) mm Hg in simultaneous analysis. We conclude
      that the Riester-Exacta portable aneroid device can be recommended for use in an
      adult population at high altitude.

PMID- 16617313
TI  - Estimation of ambient and non-ambient components of particulate matter exposure
      from a personal monitoring panel study.
AB  - To provide additional insight into factors affecting exposure to airborne
      particulate matter and the resultant health effects, we developed a method to
      estimate the ambient and nonambient components of total personal exposure. The
      ambient (or outdoor) component of total personal exposure to particulate matter
      (PM) (called ambient exposure) includes exposure to the ambient PM concentration
      while outdoors and exposure while indoors to ambient PM that has infiltrated
      indoors. The nonambient component of total personal exposure to PM (called
      nonambient exposure) refers to exposure to PM generated by indoor sources and an
      individual's personal activity. We used data collected from a personal monitoring
      study in Vancouver, Canada to demonstrate the methodology. In this study, ambient
      PM(2.5) exposure was 71% of the measured ambient PM(2.5) concentration and was
      responsible for 44% of the measured total personal PM(2.5) exposure. Regression
      analysis of the pooled data sets for ambient and total exposure against outdoor
      concentrations yielded similar slopes (0.76 for ambient and 0.77 for total) but a
      higher coefficient of determination for ambient exposure (R(2)=0.62) than for
      total exposure (R(2)=0.072). As expected, the nonambient exposure was not related
      to the ambient concentration (R(2)<10(-6)). For longitudinal analyses of the
      relationship between measured personal exposure and ambient concentrations for
      individual subjects, the correlation of total personal exposure with ambient
      concentration yielded values of Pearson's r from 0.83 to -0.68 with an average of
      0.36. The relationship was statistically significant for only five of the 16
      subjects. In contrast, the correlation of the estimated ambient exposure with
      ambient concentration yielded values of Pearson's r from 0.92 to 0.77 with an
      average of 0.88; 14 were significant. An example, taken from an epidemiologic
      analysis using the exposure data from this paper, demonstrates the usefulness of
      separating total exposure into its ambient and nonambient components.

PMID- 16617314
TI  - Lipoprotein profile in men with prostate cancer undergoing androgen deprivation
      therapy.
AB  - Sex steroids are known to modulate serum lipoproteins. Studies have suggested
      that serum testosterone levels are associated with a beneficial lipid profile.
      Androgen deprivation therapy (ADT) is employed in the treatment of recurrent and
      metastatic prostate cancer (PCa), resulting in profound hypogonadism. As male
      hypogonadism unfavorably influences lipid profile and men with PCa have high
      cardiovascular mortality, we evaluated the effects of long-term ADT on fasting
      lipids. This Cross-sectional study was conducted in a university-based research
      institution. We evaluated 44 men, 16 undergoing ADT for at least 12 months before
      the study (ADT group), 14 age-matched eugonadal men with non-metastatic PCa who
      were status post prostatectomy and/or radiotherapy and not on ADT (non-ADT group)
      and 14 age-matched eugonadal controls (Control group). None of the men had known
      history of diabetes or dyslipidemia. Mean age was similar in the three groups (P
      = 0.37). Serum total (P < 0.01) and free (P < 0.01) testosterone levels were
      lower in the ADT group compared to the other groups. Men on ADT had higher body
      mass index (BMI) compared to the other groups (P < 0.01). Men in the ADT group
      had significantly higher levels of total cholesterol compared to the other two
      groups (P = 0.03). After adjustment for BMI, men on ADT continued to have
      significantly higher fasting levels of total cholesterol (P = 0.02), LDL
      cholesterol (P = 0.04) and non-HDL cholesterol (P = 0.03) compared to the control
      group. No significant differences were seen in the levels of other lipoproteins
      between the three groups. These data show that men undergoing long-term ADT have
      higher total and LDL cholesterol than age-matched controls. Long-term prospective
      studies are needed to determine the time of onset of changes in these
      lipoproteins while on ADT and the influence of these changes on cardiovascular
      mortality.

PMID- 16617315
TI  - Reply to Kremer M et al., the JAK2 V617F mutation occurs frequently in
      myelodysplastic/myeloproliferative diseases, but is absent in true
      myelodysplastic syndromes with fibrosis.

PMID- 16617316
TI  - The JAK2 V617F mutation occurs frequently in myelodysplastic/myeloproliferative
      diseases, but is absent in true myelodysplastic syndromes with fibrosis.

PMID- 16617317
TI  - BAFF and APRIL as osteoclast-derived survival factors for myeloma cells: a
      rationale for TACI-Fc treatment in patients with multiple myeloma.

PMID- 16617318
TI  - Gene expression profiling of CD34+ cells identifies a molecular signature of
      chronic myeloid leukemia blast crisis.
AB  - Despite recent success in the treatment of early-stage disease, blastic phase
      (BP) of chronic myeloid leukemia (CML) that is characterized by rapid expansion
      of therapy-refractory and differentiation-arrested blasts, remains a therapeutic
      challenge. The development of resistance upon continuous administration of
      imatinib mesylate is associated with poor prognosis pointing to the need for
      alternative therapeutic strategies and a better understanding of the molecular
      mechanisms underlying disease progression. To identify transcriptional signatures
      that may explain pathological characteristics and aggressive behavior of BP
      blasts, we performed comparative gene expression profiling on CD34+ Ph+ cells
      purified from patients with untreated newly diagnosed chronic phase CML (CP,
      n=11) and from patients in BP (n=9) using Affymetrix oligonucleotide arrays.
      Supervised microarray data analysis revealed 114 differentially expressed genes
      (P<10(-4)), 34 genes displaying more than two-fold transcriptional changes when
      comparing CP and BP groups. While 24 of these genes were downregulated, 10 genes,
      especially suppressor of cytokine signalling 2 (SOCS2), CAMPATH-1 antigen (CD52),
      and four human leukocyte antigen-related genes were strongly overexpressed in BP.
      Expression of selected genes was validated by real-time-polymerase chain reaction
      and flow cytometry. Our data suggest the existence of a common gene expression
      profile of CML-BP and provide new insight into the molecular phenotype of blasts
      associated with disease progression and high malignancy.

PMID- 16617319
TI  - Toll-like receptors mediate proliferation and survival of multiple myeloma cells.
AB  - Multiple myeloma (MM) is an incurable B-cell malignancy characterized by
      accumulation of malignant plasma cells in bone marrow (BM) and recurrent or
      persistent infections. Toll-like receptors (TLRs) are essential in the host
      defense against infections and today 10 human TLRs (TLR1-TLR10) and one TLR
      homolog (RP105) have been characterized. B cells express several TLRs (mainly
      TLR1, 6, 7, 9, 10 and RP105) and TLR-initiated responses in B cells include
      proliferation, anti-apoptosis effect and plasma cell (PC) differentiation. The
      present study was designed to analyze the role of TLRs in MM. We show that
      frequent expressions of TLRs were detected in cell lines from MM patients
      (minimum six TLRs in each). In comparison, only few TLRs (mainly TLR1 and or
      RP105) were found expressed in PCs from BM of healthy donors. In addition, TLR
      specific ligands induce increased proliferation and survival of the MM cell
      lines, partially due to an autocrine interleukin-6 production. Importantly, we
      demonstrate that also PC from MM patients proliferates in response to TLR
      specific ligands. In conclusion, TLR-ligands may contribute to increased growth
      and survival of MM cells in MM patients.

PMID- 16617320
TI  - G1 cell-cycle arrest and apoptosis by histone deacetylase inhibition in MLL-AF9
      acute myeloid leukemia cells is p21 dependent and MLL-AF9 independent.

PMID- 16617321
TI  - Deregulated expression of fat and muscle genes in B-cell chronic lymphocytic
      leukemia with high lipoprotein lipase expression.
AB  - Lipoprotein lipase (LPL) is a prognostic marker in B-cell chronic lymphocytic
      leukemia (B-CLL) related to immunoglobulin V(H) gene (IgV(H))mutational status.
      We determined gene expression profiles using Affymetrix U133A GeneChips in two
      groups of B-CLLs selected for either high ('LPL+', n=10) or low ('LPL-', n=10)
      LPL mRNA expression. Selected genes were verified by real-time PCR in an extended
      patient cohort (n=42). A total of 111 genes discriminated LPL+ from LPL- B-CLLs.
      Of these, the top three genes associated with time to first treatment were
      Septin10, DMD and Gravin (P</=0.01). The relationship of LPL+ and LPL- B-CLL gene
      expression signatures to 52 tissues was statistically analyzed. The LPL+ B-CLL
      expression signature, represented by 64 genes was significantly related to fat,
      muscle and PB dendritic cells (P<0.001). Exploration of microarray data to define
      functional alterations related to the biology of LPL+ CLL identified two
      functional modules, fatty acid degradation and MTA3 signaling, as being altered
      with higher statistical significance. Our data show that LPL+ B-CLL cells have
      not only acquired gene expression changes in fat and muscle-associated genes but
      also in functional pathways related to fatty acid degradation and signaling which
      may ultimately influence CLL biology and clinical outcome.

PMID- 16617322
TI  - The JAK2 V617F mutation identifies a subgroup of MDS patients with isolated
      deletion 5q and a proliferative bone marrow.

PMID- 16617323
TI  - Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor
      inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic
      syndrome.
AB  - PTK787/ZK 222584 (PTK/ZK) is an oral angiogenesis inhibitor targeting vascular
      endothelial growth factor (VEGF) receptor tyrosine kinases, including VEGFR-1/Flt
      1, VEGFR-2/KDR, VEGFR-3/Flt-4, the platelet-derived growth factor receptor
      tyrosine kinase and the c-kit protein tyrosine kinase. The objective of this
      Phase I study was to evaluate the safety, tolerability, biologic activity and
      pharmacologic profile of PTK/ZK administered orally, twice daily, on a continuous
      dosing schedule in patients with primary refractory or relapsed acute myeloid
      leukemia (AML), secondary AML, poor-prognosis de novo AML or advanced
      myelodysplastic syndrome (MDS). Acute myeloid leukemia patients for whom PTK/ZK
      monotherapy was ineffective could receive PTK/ZK combined with standard induction
      chemotherapy. Sixty-three patients received PTK/ZK at doses of 500-1000 mg orally
      b.i.d. Safety and pharmacokinetic data were collected. Responses were evaluated
      according to standard bone marrow and peripheral blood criteria. At 1000 mg
      b.i.d., dose-limiting toxicities of lethargy, hypertension, nausea, emesis and
      anorexia were observed. Other adverse events related to PTK/ZK were dizziness,
      weakness, fatigue, diarrhea and pruritus; these were generally mild and
      reversible. Pharmacokinetic data showed that steady state was reached by day 14,
      there was no accumulation with repeat dosing and there was no significant
      increase in exposure at steady state beyond the maximum tolerated dose (MTD).
      Complete remission was observed in five of 17 AML patients treated with PTK/ZK
      combined with chemotherapy. In conclusion, the MTD of PTK/ZK is 750 mg orally
      b.i.d. The drug is generally well tolerated and can be given in combination with
      chemotherapy for patients with MDS and AML.

PMID- 16617324
TI  - Genomic gain at 6p21: a new cryptic molecular rearrangement in secondary
      myelodysplastic syndrome and acute myeloid leukemia.
AB  - Fluorescence in situ hybridization and comparative genomic hybridization
      characterized 6p rearrangements in eight primary and in 10 secondary myeloid
      disorders (including one patient with Fanconi anemia) and found different
      molecular lesions in each group. In primary disorders, 6p abnormalities, isolated
      in six patients, were highly heterogeneous with different breakpoints along the
      6p arm. Reciprocal translocations were found in seven. In the 10 patients with
      secondary acute myeloid leukemia/myelodysplastic syndrome (AML/MDS), the short
      arm of chromosome 6 was involved in unbalanced translocations in 7. The other
      three patients showed full or partial trisomy of the 6p arm, that is, i(6)(p10)
      (one patient) and dup(6)(p) (two patients). In 5/7 patients with unbalanced
      translocations, DNA sequences were overrepresented at band 6p21 as either cryptic
      duplications (three patients) or cryptic low-copy gains (two patients). In the
      eight patients with cytogenetic or cryptic 6p gains, we identified a common
      overrepresented region extending for 5-6 megabases from the TNF gene to the ETV-7
      gene. 6p abnormalities were isolated karyotype changes in four patients.
      Consequently, in secondary AML/MDS, we hypothesize that 6p gains are major
      pathogenetic events arising from acquired and/or congenital genomic instability.

PMID- 16617325
TI  - The role of the nuclear Akt activation and Akt inhibitors in all-trans-retinoic
      acid-differentiated HL-60 cells.
AB  - The pharmacological inhibitors of phosphoinositide 3-kinase (PI3K)/Akt pathway
      have been proposed in the treatment of leukemia based on their antiproliferative
      effects. However, several studies demonstrated the activation of PI3K in the
      nuclei of all-trans-retinoic acid (ATRA) - differentiated HL-60 cells, raising
      the possibility that PI3K/Akt-inhibitors may block antitumor properties of
      retinoids. The aim of the present study was to investigate the possible
      activation of nuclear Akt in ATRA-treated cells and to test the effects of Akt
      inhibitors on ATRA-mediated differentiation. The Akt-activity was found to be
      increased in the nuclei and lysates of ATRA-differentiated HL-60 and NB4 cells.
      The down-modulation of the expression of Akt protein in HL-60 cells using siRNA
      reduces the CD11b expression in ATRA-treated cells. The treatment of both cell
      lines with the commercially available Akt inhibitors inhibited the growth of both
      control and ATRA-treated cells. Akt-inhibitors had no inhibitory effects on ATRA
      mediated growth arrest and the expression of CD11b in HL-60 cells, but increased
      the percentage of control cells expressing CD11b. In contrast, the presence of
      Akt inhibitors reduced the expression of CD11b in ATRA-treated NB4 cells.

PMID- 16617326
TI  - HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed
      cryoglobulinemia and B-cell clonal proliferations.
AB  - We demonstrate that in three cases of MC (two with immunocytoma), the IgM-RF+
      component of their cryoprecipitated represents the circulating counterpart of the
      B-cell receptor (BCR) of the monoclonal overexpanded B-cell population. These
      IgMs were isolated and used to demonstrate a crossreactivity against both
      hepatitis C virus (HCV) NS3 antigen and the Fc portion of IgG. Epitopes were
      identified in a fraction of exemplary samples by using epitope excision approach
      (NS(31250-1334) and IgG Fc(345-355)). The same phenomenon of crossreactivity has
      been shown to occur in vivo after immunization of a mouse with the NS3(1251-1270)
      peptide. To verify if the same reaction was also present in MC samples
      characterized by an oligo/polyclonal B-cell proliferation, IgM crossreactivity
      was tested in 14 additional samples. Five out of the 14 were reactive against HCV
      NS3 and 11 out of 14 were reactive against IgG-Fc peptide. The data support the
      role of HCV NS3 antigen in a subset of patients with MC, whereas the high
      frequency of the IgG-Fc epitope suggests that these B cells originate from
      precursors strongly selected for auto-IgG specificity. We suggest that engagement
      of specific BCRs by NS3 (or NS3-immunocomplex) antigen could explain the
      prevalence of IgM cryoglobulins in these patients.

PMID- 16617327
TI  - Inhibition of p38alpha MAPK enhances proteasome inhibitor-induced apoptosis of
      myeloma cells by modulating Hsp27, Bcl-X(L), Mcl-1 and p53 levels in vitro and
      inhibits tumor growth in vivo.
AB  - Inhibition of p38 kinase blocks the production of tumor-promoting factors in the
      multiple myeloma (MM) bone marrow microenvironment. Proteasome inhibitors MG132
      and bortezomib have been shown to have direct cytotoxic effects on MM cells. We
      show that a selective inhibitor of p38alpha, SCIO-469, enhances the ability of
      MG132 and bortezomib to induce the apoptosis of MM cells. Previously, we showed
      that p38 inhibition with SCIO-469 enhances MM cytotoxicity of bortezomib by
      inhibiting the transient expression and phosphorylation of Hsp27, a downstream
      target of p38. Here we show that continued treatment of MM cells with bortezomib
      leads to a SCIO-469-enhanced downregulation of Hsp27 and to increased MM
      apoptosis. Furthermore, we show that p38 inhibition enhances the bortezomib
      induced MM apoptosis by upregulation of p53 and downregulation of Bcl-X(L) and
      Mcl-1. In a mouse xenograft plasmacytoma model of MM, we found that inhibiting
      p38 augments the effects of bortezomib in decreasing MM tumor growth in vivo.
      Thus, in addition to its role in suppressing an activated MM microenvironment, co
      treatment with a p38 inhibitor, such as SCIO-469, may enhance the cytotoxicity of
      bortezomib by modulating pro-apoptotic and anti-apoptotic factors in MM cells,
      suggesting great potential for co-therapy.

PMID- 16617328
TI  - Molecular and phenotypic characterization of human amniotic fluid cells and their
      differentiation potential.
AB  - The main goal of the study was to identify a novel source of human multipotent
      cells, overcoming ethical issues involved in embryonic stem cell research and the
      limited availability of most adult stem cells. Amniotic fluid cells (AFCs) are
      routinely obtained for prenatal diagnosis and can be expanded in vitro;
      nevertheless current knowledge about their origin and properties is limited.
      Twenty samples of AFCs were exposed in culture to adipogenic, osteogenic,
      neurogenic and myogenic media. Differentiation was evaluated using
      immunocytochemistry, RT-PCR and Western blotting. Before treatments, AFCs showed
      heterogeneous morphologies. They were negative for MyoD, Myf-5, MRF4, Myogenin
      and Desmin but positive for osteocalcin, PPARgamma2, GAP43, NSE, Nestin, MAP2,
      GFAP and beta tubulin III by RT-PCR. The cells expressed Oct-4, Rex-1 and Runx-1,
      which characterize the undifferentiated stem cell state. By immunocytochemistry
      they expressed neural-glial proteins, mesenchymal and epithelial markers. After
      culture, AFCs differentiated into adipocytes and osteoblasts when the predominant
      cellular component was fibroblastic. Early and late neuronal antigens were still
      present after 2 week culture in neural specific media even if no neuronal
      morphologies were detectable. Our results provide evidence that human amniotic
      fluid contains progenitor cells with multi-lineage potential showing stem and
      tissue-specific gene/protein presence for several lineages.

PMID- 16617329
TI  - Isolation and characterization of Xenopus laevis homologs of the mouse inv gene
      and functional analysis of the conserved calmodulin binding sites.
AB  - The homozygous inv (inversion of embryonic turning) mouse mutant shows situs
      inversus and polycystic kidney disease, both of which result from the lack of the
      inv gene. Previously, we suggested that inv may be important for the left-right
      axis formation, not only in mice but also in Xenopus, and that calmodulin
      regulates this inv protein function. Here, we isolated and characterized two
      Xenopus laevis homologs (Xinv-1 and Xinv-2) of the mouse inv gene, and performed
      functional analysis of the conserved IQ motifs that interact with calmodulin.
      Xinv-1 expresses early in development in the same manner as mouse inv does.
      Unexpectedly, a full-length Xenopus inv mRNA did not randomize cardiac
      orientation when injected into Xenopus embryos, which is different from mouse inv
      mRNA. Contrary to mouse inv mRNA, Xenopus inv mRNA with mutated IQ randomized
      cardiac orientation. The present study indicates that calmodulin binding sites
      (IQ motifs) are crucial in controlling the biological activity of both mouse and
      Xenopus inv proteins. Although mouse and Xenopus inv genes have a quite similar
      structure, the interaction with calmodulin and IQ motifs of Xenopus inv and mouse
      inv proteins may regulate their function in different ways.

PMID- 16617330
TI  - Chromatin-binding in vivo of the erythroid kruppel-like factor, EKLF, in the
      murine globin loci.
AB  - EKLF is an erythroid-specific, zinc finger-containing transcription factor
      essential for the activation of the mammalian beta globin gene in erythroid cells
      of definitive lineage. We have prepared a polyclonal anti-mouse EKLF antibody
      suitable for Western blotting and immunoprecipitation (IP) qualities, and used it
      to define the expression patterns of the EKLF protein during mouse erythroid
      development. We have also used this antibody for the chromatin
      immunoprecipitation (ChIP) assay. EKLF was found to bind in vivo at both the
      mouse beta-major-globin promoter and the HS2 site of beta-LCR in the mouse
      erythroleukemia cells (MEL) in a DMSO-inducible manner. The DMSO-induced bindings
      of EKLF as well as three other proteins, namely, RNA polymerase II, acetylated
      histone H3, and methylated histone H3, were not abolished but significantly
      lowered in CB3, a MEL-derived cell line with null-expression of p45/NF-E2, an
      erythroid-enriched factor needed for activation of the mammalian globin loci.
      Interestingly, binding of EKLF in vivo was also detected in the mouse alpha-like
      globin locus, at the adult alpha globin promoter and its far upstream regulatory
      element alpha-MRE (HS26). This study provides direct evidence for EKLF-binding in
      vivo at the major regulatory elements of the mouse beta-like globin gene clusters
      the data also have interesting implications with respect to the role of EKLF
      chromatin interaction in mammalian globin gene regulation.

PMID- 16617331
TI  - Overexpression of Aurora-A kinase promotes tumor cell proliferation and inhibits
      apoptosis in esophageal squamous cell carcinoma cell line.
AB  - Aurora-A kinase, a serine/threonine protein kinase, is a potential oncogene.
      Amplification and overexpression of Aurora-A have been found in several types of
      human tumors, including esophageal squamous cell carcinoma (ESCC). It has been
      demonstrated that cells overexpressing Aurora-A are more resistant to cisplatin
      induced apoptosis. However, the molecular mechanisms mediating these effects
      remain largely unknown. In this report, we showed that overexpression of Aurora-A
      through stable transfection of pEGFP-Aurora-A in human ESCC KYSE150 cells
      significantly promoted cell proliferation and inhibited cisplatin- or UV
      irradiation-induced apoptosis. Cleavages of caspase-3 and poly (ADP-ribose)
      polymerase (PARP) in Aurora-A overexpressing cells were substantially reduced
      after cisplatin or UV treatment. Furthermore, we found that silencing of
      endogenous Aurora-A kinase with siRNA substantially enhanced sensitivity to
      cisplatin- or UV-induced apoptosis in human ESCC EC9706 cells. In parallel,
      overexpression of Aurora-A potently upregulated the expression of Bcl-2.
      Moreover, the knockdown of Bcl-2 by siRNA abrogated the Aurora-A's effect on
      inhibiting apoptosis. Taken together, these data provide evidence that Aurora-A
      overexpression promoting cell proliferation and inhibiting apoptosis, suggesting
      a novel mechanism that is closely related to malignant phenotype and anti-cancer
      drugs resistance of ESCC cells.

PMID- 16617332
TI  - Microfilament-binding properties of N-terminal extension of the isoform of smooth
      muscle long myosin light chain kinase.
AB  - Myosin light chain kinases (MLCK) phosphorylate the regulatory light chain of
      myosin II in thick filaments and bind to F-actin-containing thin filaments with
      high affinity. The ability of short myosin light chain kinase (S-MLCK) to bind F
      actin is structurally attributed to the DFRXXL regions in its N-terminus. The
      long myosin light chain kinase (L-MLCK) has two additional DFRXXL motifs and six
      Ig-like modules in its N-terminal extension. The six Ig-like modules are capable
      of binding to stress fibers independently. Our results from the imaging analysis
      demonstrated that the first two intact Ig-like modules (2Ig) in N-terminal
      extension of L-MLCK is the minimal binding module required for microfilament
      binding. Binding assay confirmed that F-actin was able to bind 2Ig.
      Stoichiometries of 2Ig peptide were similar for myofilament or pure F-actin. The
      binding affinities were slightly lower than 5DFRXXL peptide as reported
      previously. Similar to DFRXXL peptides, the 2Ig peptide also caused efficient F
      actin bundle formation in vitro. In the living cell, over-expression of 2Ig
      fragment increased "spike"-like protrusion formation with over-bundled F-actin.
      Our results suggest that L-MLCK may act as a potent F-actin bundling protein via
      its DFRXXL region and the 2Ig region, implying that L-MLCK plays a role in
      cytoskeleton organization.

PMID- 16617333
TI  - Identification of AtENT3 as the main transporter for uridine uptake in
      Arabidopsis roots.
AB  - Previous studies have shown that Arabidopsis equilibrative nucleoside
      transporters (AtENTs) possess transport activities when produced in yeast cells
      and are differentially expressed in Arabidopsis organs. Herein, we report further
      analysis on the nucleoside transport activities and transcriptional patterns of
      AtENT members. The recombinant proteins of AtENTs 3, 6, and 7, but not those of
      AtENTs 1, 2, 4, and 8, were found to transport thymidine with high affinity.
      Contrary to previous suggestion that AtENT1 may not transport uridine, this work
      showed that recombinant AtENT1 was a pH-dependent and high-affinity transporter
      of uridine. When grown on MS plates, the AtENT3 knockout plants were more
      tolerant to the cytotoxic uridine analog 5-fluorouridine than wild-type plants
      and the knockout plants of AtENT1 or AtENT6. Consistent with this observation,
      the AtENT3 knockout line exhibited a significantly decreased ability to take up
      [(3)H]uridine via the roots when compared with wild-type plants and the plants
      with mutated AtENT1 or AtENT6. This indicates that AtENT3, but not AtENTs 1 and
      6, is the main transporter for uridine uptake in Arabidopsis roots. The
      transcription of AtENTs 1, 3, 4, 6, 7, and 8 was regulated in a complex manner
      during leaf development and senescence. In contrast, the six AtENT members were
      coordinately induced during seed germination. This work provides new information
      on the transport properties of recombinant AtENT proteins and new clues for
      future studies of the in vivo transport activities and physiological functions of
      the different ENT proteins in Arabidopsis plants.

PMID- 16617334
TI  - Transcriptional diversity of DMRT1 (dsx- and mab3-related transcription factor 1)
      in human testis.
AB  - Recent advances in the evolutionary genetics of sex determination indicate that
      the only molecular similarity in sex determination found so far among phyla is
      between the fly doublesex, worm mab-3 and vertebrate DMRT1(dsx- and mab3-related
      transcription factor 1) /DMY genes. Each of these factors encodes a zinc-finger
      like DNA-binding motif, DM domain. Insights into the evolution and functions of
      human DMRT1 gene could reveal evolutionary mechanisms of sexual development. Here
      we report the identification and characterization of multiple isoforms of human
      DMRT1 in the testis. These transcripts encode predicted proteins with 373, 275
      and 175 amino acids and they were generated by alternative splicing at 3' region.
      Expression level of DMRT1a is higher than those of both DMRT1b and c, and the
      DMRT1c expression was the lowest in testis, based on comparisons of mean values
      from real-time fluorescent quantitative RT-PCR analysis. Both DMRT1b and c result
      from exonization of intronic sequences, including the exonization of an Alu
      element. A further search for Alu elements within the DMRT1 gene demonstrated
      that all 99 Alu elements are non-randomly distributed among the non-coding
      regions on both directions. These new characteristics of DMRT1 would have an
      important impact on the evolution of sexual development mechanisms.

PMID- 16617335
TI  - Primary evidence for involvement of IP3 in heat-shock signal transduction in
      Arabidopsis.
AB  - The role of inositol 1,4,5-trisphosphate (IP(3)) in transducing heat-shock (HS)
      signals was examined in Arabidopsis. The whole-plant IP(3) level increased within
      1 min of HS at 37 degrees C. After 3 min of HS, the IP(3) level reached a maximum
      2.5 fold increase. Using the transgenic Arabidopsis plants that have AtHsp18.2
      promoter-beta-glucuronidase (GUS) fusion gene, it was found that the level of GUS
      activity was up-regulated by the addition of caged IP(3) at both non-HS and HS
      temperatures and was down-regulated by the phospholipase C (PLC) inhibitors {1-[6
      ((17beta-3-Methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl]-2,5
      pyrrolidinedione}(U-73122). The intracellular-free calcium ion concentration
      ([Ca(2+)](i)) increased during HS at 37 degrees C in suspension-cultured
      Arabidopsis cells expressing apoaequorin. Treatment with U-73122 prevented the
      increase of [Ca(2+)](i) to some extent. Above results provided primary evidence
      for the possible involvement of IP(3) in HS signal transduction in higher plants.

PMID- 16617336
TI  - A liposome-PCR assay for the ultrasensitive detection of biological toxins.
AB  - We describe an ultrasensitive immunoassay for detecting biotoxins that uses
      liposomes with encapsulated DNA reporters, and ganglioside receptors embedded in
      the bilayer, as a detection reagent. After immobilization of the target biotoxin
      by a capture antibody and co-binding of the detection reagent, the liposomes are
      ruptured to release the reporters, which are quantified by real-time PCR. Assays
      for cholera and botulinum toxins are several orders of magnitude more sensitive
      than current detection methods.

PMID- 16617337
TI  - T cell- and B cell-independent adaptive immunity mediated by natural killer
      cells.
AB  - It is commonly believed that only T lymphocytes and B lymphocytes expressing
      recombination-dependent antigen-specific receptors mediate contact
      hypersensitivity responses to haptens. Here we found that mice devoid of T cells
      and B cells demonstrated substantial contact hypersensitivity responses to 2,4
      dinitrofluorobenzene and oxazolone. Those responses were adaptive in nature, as
      they persisted for at least 4 weeks and were elicited only by haptens to which
      mice were previously sensitized. No contact hypersensitivity was induced in mice
      lacking all lymphocytes, including natural killer cells. Contact hypersensitivity
      responses were acquired by such mice after adoptive transfer of natural killer
      cells from sensitized donors. Transferable hapten-specific memory resided in a
      Ly49C-I(+) natural killer subpopulation localized specifically in donor livers.
      These observations indicate that natural killer cells can mediate long-lived,
      antigen-specific adaptive recall responses independent of B cells and T cells.

PMID- 16617338
TI  - Oregano, thyme and clove-derived flavors and skin sensitizers activate specific
      TRP channels.
AB  - Carvacrol, eugenol and thymol are major components of plants such as oregano,
      savory, clove and thyme. When applied to the tongue, these flavors elicit a warm
      sensation. They are also known to be skin sensitizers and allergens. The
      transient receptor potential channel (TRPV3) is a warm-sensitive Ca2+-permeable
      cation channel highly expressed in the skin, tongue and nose. Here we show that
      TRPV3 is strongly activated and sensitized by carvacrol, thymol and eugenol.
      Tongue and skin epithelial cells respond to carvacrol and eugenol with an
      increase in intracellular Ca2+ levels. We also show that this TRPV3 activity is
      strongly potentiated by phospholipase C-linked, G protein-coupled receptor
      stimulation. In addition, carvacrol activates and rapidly desensitizes TRPA1,
      which may explain the pungency of oregano. Our results support a role for
      temperature-sensitive TRP channels in chemesthesis in oral and nasal epithelium
      and suggest that TRPV3 may be a molecular target of plant-derived skin
      sensitizers.

PMID- 16617339
TI  - Optimal representation of sensory information by neural populations.
AB  - Sensory information is encoded by populations of neurons. The responses of
      individual neurons are inherently noisy, so the brain must interpret this
      information as reliably as possible. In most situations, the optimal strategy for
      decoding the population signal is to compute the likelihoods of the stimuli that
      are consistent with an observed neural response. But it has not been clear how
      the brain can directly compute likelihoods. Here we present a simple and
      biologically plausible model that can realize the likelihood function by
      computing a weighted sum of sensory neuron responses. The model provides the
      basis for an optimal decoding of sensory information. It explains a variety of
      psychophysical observations on detection, discrimination and identification, and
      it also directly predicts the relative contributions that different sensory
      neurons make to perceptual judgments.

PMID- 16617340
TI  - Correlating whisker behavior with membrane potential in barrel cortex of awake
      mice.
AB  - To investigate synaptic events underlying sensory perception, we made whole-cell
      membrane potential recordings of barrel cortex neurons in awake mice while
      recording whisker-related behavior. During quiet periods, we recorded slow, large
      amplitude membrane potential changes, which switched during whisking to small,
      fast fluctuations that were correlated with whisker position. Robust subthreshold
      responses were evoked by passive whisker stimulation during quiet behavior and by
      active whisker contact with an object.

PMID- 16617341
TI  - Bipolar cell pathways for color and luminance vision in a dichromatic mammalian
      retina.
AB  - The mammalian retina is fundamentally dichromatic, with trichromacy only recently
      emerging in some primates. In dichromats, an array of short wavelength-sensitive
      (S, blue) and middle wavelength-sensitive (M, green) cones is sampled by
      approximately ten bipolar cell types, and the sampling pattern determines how
      retinal ganglion cells and ultimately higher visual centers encode color and
      luminance. By recording from cone-bipolar cell pairs in the retina of the ground
      squirrel, we show that the bipolar cell types sample cone signals in three ways:
      one type receives input exclusively from S-cones, two types receive mixed S/M
      cone input and the remaining types receive an almost pure M-cone signal. Bipolar
      cells that carry S- or M-cone signals can have a role in color discrimination and
      may contact color-opponent ganglion cells. Bipolar cells that sum signals from S-
      and M-cones may signal to ganglion cells that encode luminance.

PMID- 16617343
TI  - Mechanistic principles of nanoparticle evolution to zeolite crystals.
AB  - Precursor nanoparticles that form spontaneously on hydrolysis of
      tetraethylorthosilicate in aqueous solutions of tetrapropylammonium (TPA)
      hydroxide evolve to TPA-silicalite-1, a molecular-sieve crystal that serves as a
      model for the self-assembly of porous inorganic materials in the presence of
      organic structure-directing agents. The structure and role of these nanoparticles
      are of practical significance for the fabrication of hierarchically ordered
      porous materials and molecular-sieve films, but still remain elusive. Here we
      show experimental findings of nanoparticle and crystal evolution during room
      temperature ageing of the aqueous suspensions that suggest growth by aggregation
      of nanoparticles. A kinetic mechanism suggests that the precursor nanoparticle
      population is distributed, and that the 5-nm building units contributing most to
      aggregation only exist as an intermediate small fraction. The proposed oriented
      aggregation mechanism should lead to strategies for isolating or enhancing the
      concentration of crystal-like nanoparticles.

PMID- 16617344
TI  - Nanoscale avalanche photodiodes for highly sensitive and spatially resolved
      photon detection.
AB  - Integrating nanophotonics with electronics could enhance and/or enable
      opportunities in areas ranging from communications and computing to novel
      diagnostics. Light sources and detectors are important elements for integration,
      and key progress has been made using semiconducting nanowires and carbon
      nanotubes to yield electrically driven sources and photoconductor detectors.
      Detection with photoconductors has relatively poor sensitivity at the nanometre
      scale, and thus large amplification is required to detect low light levels and
      ultimately single photons with reasonable response time. Here, we report
      avalanche multiplication of the photocurrent in nanoscale p-n diodes consisting
      of crossed silicon-cadmium sulphide nanowires. Electrical transport and optical
      measurements demonstrate that the nanowire avalanche photodiodes (nanoAPDs) have
      ultrahigh sensitivity with detection limits of less than 100 photons, and
      subwavelength spatial resolution of at least 250 nm. Crossed nanowire arrays also
      show that nanoAPDs are reproducible and can be addressed independently without
      cross-talk. NanoAPDs and arrays could open new opportunities for ultradense
      integrated systems, sensing and imaging applications.

PMID- 16617342
TI  - Endocytosis and synaptic removal of NR3A-containing NMDA receptors by
      PACSIN1/syndapin1.
AB  - A key step in glutamatergic synapse maturation is the replacement of
      developmentally expressed N-methyl-D-aspartate receptors (NMDARs) with mature
      forms that differ in subunit composition, electrophysiological properties and
      propensity to elicit synaptic plasticity. However, the mechanisms underlying the
      removal and replacement of synaptic NMDARs are poorly understood. Here we
      demonstrate that NMDARs containing the developmentally regulated NR3A subunit
      undergo rapid endocytosis from the dendritic plasma membrane in cultured rat
      hippocampal neurons. This endocytic removal is regulated by PACSIN1/syndapin1,
      which directly and selectively binds the carboxy-terminal domain of NR3A through
      its NPF motifs and assembles a complex of proteins including dynamin and
      clathrin. Endocytosis of NR3A by PACSIN1 is activity dependent, and disruption of
      PACSIN1 function causes NR3A accumulation at synaptic sites. Our results reveal a
      new activity-dependent mechanism involved in the regulation of NMDAR expression
      at synapses during development, and identify a brain-specific endocytic adaptor
      that confers spatiotemporal and subunit specificity to NMDAR endocytosis.

PMID- 16617345
TI  - Room-temperature miscibility gap in LixFePO4.
AB  - The rechargeable lithium-ion cell is an advanced energy-storage system. However,
      high cost, safety hazards, and chemical instability prohibit its use in large
      scale applications. An alternative cathode material, LiFePO(4), solves these
      problems, but has a kinetic problem involving strong electron/hole localization.
      One reason for this is believed to be the limited carrier density in the fixed
      monovalent Fe(3+)PO(4)/LiFe(2+)PO(4) two-phase electrode reaction in LixFePO4.
      Here, we provide experimental evidence that LixFePO4, at room temperature, can be
      described as a mixture of the Fe(3+)/Fe(2+) mixed-valent intermediate
      LialphaFePO4 and Li1-betaFePO4 phases. Using powder neutron diffraction, the site
      occupancy numbers for lithium in each phase were refined to be alpha=0.05 and 1
      beta=0.89. The corresponding solid solution ranges outside the miscibility gap
      (0<x<alpha,1-beta<x<1) were detected by the anomaly in the configurational
      entropy, and also by the deviation of the open-circuit voltage from the constant
      equilibrium potential. These findings encourage further improvement of this
      important class of compounds at ambient temperatures.

PMID- 16617346
TI  - Phase separation in superoxygenated La2-xSrxCuO4+y.
AB  - The complex interplay between superconducting and magnetic phases remains poorly
      understood. Here, we report on the phase separation of doped holes into separate
      magnetic and superconducting regions in superoxygenated La(2-x)Sr(x)CuO(4+y),
      with various Sr contents. Irrespective of Sr-doping, excess oxygen raises the
      superconducting onset to 40 K with a coexisting magnetic spin-density wave that
      also orders near 40 K in each of our samples. The magnetic region is closely
      related to the anomalous, 1/8-hole-doped magnetic versions of La(2)CuO(4),
      whereas the superconducting region is optimally doped. The two phases are
      probably the only truly stable ground states in this region of the phase diagram.
      This simple two-component system is a candidate for electronic phase separation
      in cuprate superconductors, and a key to understanding seemingly conflicting
      experimental observations.

PMID- 16617347
TI  - Plasticity, healing and shakedown in sharp-asperity nanoindentation.
AB  - Spatially localized stress fields produced by instrumented, sharp indentation
      probes are a route to testing the mechanical properties of materials at the
      smallest length scales. Here we provide direct experimental measurement of
      indentation plasticity with contact strain fields involving up to a few thousand
      atoms. We observe two types of nanoscale plasticity: on the pristine surface,
      high-resolution sensing shows an overall smooth, remarkably reversible
      indentation response interjected by sudden discrete drops in indenter load. The
      jumps often occur in pairs with pop-in motion during loading healed by a
      corresponding pop-out motion on the unload stroke to define a compact hysteresis
      loop. Despite the general reversibility, cyclic indentation at a single sample
      position leads to a subtle plastic ratchet and shakedown behaviour with
      displacements correlated to the underlying gold lattice constant. Our results
      concur with a previously established picture of thermally activated atomistic
      plasticity, but suggest a new mechanism at reduced scales that suppresses
      permanent mass transport.

PMID- 16617348
TI  - Photophysics of dopamine-modified quantum dots and effects on biological systems.
AB  - Semiconductor quantum dots (QDs) have been widely used for fluorescent labelling.
      However, their ability to transfer electrons and holes to biomolecules leads to
      spectral changes and effects on living systems that have yet to be exploited.
      Here we report the first cell-based biosensor based on electron transfer between
      a small molecule (the neurotransmitter dopamine) and CdSe/ZnS QDs. QD-dopamine
      conjugates label living cells in a redox-sensitive pattern: under reducing
      conditions, fluorescence is only seen in the cell periphery and lysosomes. As the
      cell becomes more oxidizing, QD labelling appears in the perinuclear region,
      including in or on mitochondria. With the most-oxidizing cellular conditions, QD
      labelling throughout the cell is seen. Phototoxicity results from the creation of
      singlet oxygen, and can be reduced with antioxidants. This work suggests methods
      for the creation of phototoxic drugs and for redox-specific fluorescent labelling
      that are generalizable to any QD conjugated to an electron donor.

PMID- 16617349
TI  - The SHP-1 protein tyrosine phosphatase negatively modulates glucose homeostasis.
AB  - The protein tyrosine phosphatase SHP-1 is a well-known inhibitor of activation
      promoting signaling cascades in hematopoietic cells but its potential role in
      insulin target tissues is unknown. Here we show that Ptpn6(me-v/me-v) (also known
      as viable motheaten) mice bearing a functionally deficient SHP-1 protein are
      markedly glucose tolerant and insulin sensitive as compared to wild-type
      littermates, as a result of enhanced insulin receptor signaling to IRS-PI3K-Akt
      in liver and muscle. Downregulation of SHP-1 activity in liver of normal mice by
      adenoviral expression of a catalytically inert mutant of SHP-1, or after small
      hairpin RNA-mediated SHP-1 silencing, further confirmed this phenotype. Tyrosine
      phosphorylation of CEACAM1, a modulator of hepatic insulin clearance, and
      clearance of serum [125I]-insulin were markedly increased in SHP-1-deficient mice
      or SHP-1-deficient hepatic cells in vitro. These findings show a novel role for
      SHP-1 in the regulation of glucose homeostasis through modulation of insulin
      signaling in liver and muscle as well as hepatic insulin clearance.

PMID- 16617350
TI  - [PLAC1/CP1 gene expression and autologous humoral immunity in gastric cancer
      patients].
AB  - OBJECTIVE: To investigate PLAC1/CP1 as a potential candidate gene in gastric
      cancer therapy. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR)
      method was used to detect the expression of PLAC1/CP1 mRNA in gastric cancer
      tissues and paired adjacent non-cancerous tissues resected from 28 patients with
      gastric cancer. Specific antibodies against PLAC1/CP1 were also detected by ELISA
      method in gastric cancer patients. RESULTS: Fourteen (50%,14/28) out of the 28
      gastric cancer samples were PLAC1/CP1 mRNA positive. Of the 28 serum samples
      tested,eight (29%,8/28) displayed positive seroreactivity against PLAC1/CP1
      antigen, accounting for 57% (8/14) of PLAC1/CP1 mRNA positive samples.
      CONCLUSION: PLAC1/CP1 mRNA was expressed in high frequency and induced
      spontaneous antibody responses in gastric cancer patients. PLAC1/CP1 may be a
      valuable candidate antigen in gastric cancer immunotherapy.

PMID- 16617351
TI  - [Chemotactic and mitogenic effect of rat chemokine-like factor 1 on aortic smooth
      muscle cells].
AB  - OBJECTIVE: To study the effects of rat chemokine-like factor 1 (rCklf1) on
      chemotaxis and proliferation of rat aortic smooth muscle cells(ASMC). METHODS:
      The recombinant eukaryotic expression vector pcDNA3.1/rCklf1 was transiently
      transfected into 293T cells. The supernatants were harvested for chemotactic and
      proliferation assays. pcDNA3.1/rCklf1 was also transfected into ASMC and the
      proliferation of transfected cells was detected by MTT assays. RESULTS: The 10
      fold diluted supernatants of pcDNA3.1/rCklf1 transfected 293T cells had
      chemotactic effects on rat ASMC, which could be inhibited by pertussis toxin at
      the concentration of 10 microg/L. Furthermore, the 10 fold diluted supernatants
      of rCklf1 transfected 293T cells promoted the proliferation of ASMC (1.3 fold
      compared with the control) and transient overexpression of rCklf1 in ASMC had
      promoting activities on the proliferation of rat ASMC (1.5 fold compared with the
      control at 72 h). CONCLUSION: rCklf1 has mitogenic and GiPCR-dependent
      chemotactic effects on rat ASMC,indicating that rCklf1 may be involved in the
      pathological process of atherosclerosis.

PMID- 16617352
TI  - [Effect of gamma-aminobutyric acid B receptor on nitric oxide/nitric oxide
      synthase system during recurrent febrile seizures].
AB  - OBJECTIVE: To explore the effect of gamma-aminobutyric acid B receptor
      (GABA(B)R)on nitric oxide (NO)/nitric oxide synthase (NOS) system during
      recurrent febrile seizures (FS). METHODS: Sprague-Dawley rats aged 21 days were
      randomly divided into four groups:control group, FS group, FS + baclofen group,
      FS + phaclofen group. FS in rats were induced ten times in a bath of warm
      water,once every 2 days. The plasma level of NO was detected by the
      spectrophotometer; the expression of nNOS mRNA was examined by in situ
      hybridization; the expression of nNOS protein was observed by
      immunohistochemistry. RESULTS: Compared with those in FS group,the plasma level
      of NO decreased [(19.02+/-9.31) micromol/L vs (40.03+/-9.12)micromol/L], and the
      expression of nNOS was down-regulated in FS + baclofen group; the plasma level of
      NO increased [(66.46+/-8.15) micromol/L vs (40.03+/-9.12) micromol/L] and the
      expression of nNOS was up-regulated in FS + phaclofen group. CONCLUSION: GABA(B)R
      modulated the expression of NO/NOS system during recurrent FS.

PMID- 16617353
TI  - [Impact of hydrogen sulfide donor on experimental pulmonary hypertension induced
      by high pulmonary flow and endogenous carbon monoxide/heme oxygenase pathway].
AB  - OBJECTIVE: To explore the possible impact of hydrogen sulfide donor-NaHS (sodium
      hydrosulfide) on experimental pulmonary artery structural remodeling induced by
      high pulmonary flow and endogenous carbon monoxide/heme oxygenase pathway.
      METHODS: Thirty-two male SD rats were randomly divided into shunt group (n=8),
      shunt+NaHS group (n=8), sham group (n=8) and sham+NaHS group (n=8). Rats in shunt
      group and shunt+NaHS group were subjected to an abdominal aorta-inferior vena
      cava shunt to create an animal model of high pulmonary flow. In the sham group
      and sham+NaHS group, rats experienced the same experimental processes except the
      shunting procedure. After 11 weeks of operation, systolic pulmonary artery
      pressure (SPAP) was detected using a right cardiac catheterization procedure. The
      percentage of muscularized artery (MA), partly muscularized artery (PMA) and non
      muscularized artery (NMA) was calculated. Relative medial thickness (RMT) and
      relative medial area (RMA) of MA were observed under optical-microscope,
      respectively. The ultra-structure of pulmonary arteries was observed under
      electro-microscope. Lung tissue carbon monoxide (CO) was measured. Western-blot
      was used to analyze lung tissue heme oxygenase (HO-1) protein expression.
      RESULTS: After 11 weeks of shunt, compared with sham group, SPAP in shunt group
      increased by 48.6%.The percentages of MA and PMA increased by 74.2% and 90.9%,
      but the percentage of NMA decreased 32.2%, respectively, in rats of shunt group
      as compared with that of sham group. In contrast to those in sham group, RMT and
      RMA in median MA and small MA of rats in shunt group increased by 83.6%, 86.9%,
      and 74.4%, 39.9%, respectively. Ultra-structural changes in rats of shunt group
      showed that endothelial cells were swollen and denatured, inner elastic membrane
      became irregular, and smooth muscle cells became synthetic phenotype. The sham
      and shunt groups did not differ significantly in CO and HO-1 protein expression
      of lung tissues. In contrast to that of shunt group, SPAP in rats of shunt+NaHS
      group decreased by 19.8%. The percentages of MA and PMA decreased by 14.4% and
      12.2%, but the percentage of NMA increased 13.9%, respectively, in rats of
      shunt+NaHS group as compared with that of shunt group. In contrast to those of
      shunt group, RMT and RMA in median MA and small MA in rats of shunt+NaHS group
      decreased by 16.2%, 14.3%, and 26.9%, 14.3%, respectively. For rats in shunt+NaHS
      group ultra-structural changes showed that flat endothelial cells, inner elastic
      membrane became regular, and smooth muscle cells were contractile phenotype. The
      content of CO increased by 25.5% and the HO-1 protein expression increased by
      114.3% in shunt+NaHS group as compared with those of shunt group. CONCLUSION:
      NaHS might prevent pulmonary hypertension and pulmonary artery structural
      remodeling induced by high pulmonary flow, and its mechanism might be associated
      with the changes in endogenous CO/HO pathway.

PMID- 16617354
TI  - [Effect of hydrogen sulfide on Bleomycin-induced pulmonary fibrosis in rats].
AB  - OBJECTIVE: To explore the change of endogenous hydrogen sulfide and the effect of
      exogenously applied H(2)S on Bleomycin-induced pulmonary fibrosis in rats.
      METHODS: (1) Forty-eight male Wistar rats were randomly divided into control
      group, fibrosis group, fibrosis+NaHS-low group (1.4 micromol/kg, bid
      intraperitoneally) and fibrosis+NaHS-high group (7.0 micromol/kg, bid
      intraperitoneally). Pulmonary fibrosis was induced by intratracheal instillation
      of bleomycin. The control group and pulmonary fibrosis group were injected with
      the same volume of normal saline. Pulmonary pathology changes were observed, the
      plasma H(2)S concentration,the activity of CSE in lung tissue and the contents of
      MDA, hydroxyproline were detected on the 7th and 28th days respectively after
      bleomycin administration. CSE mRNA was also measured using quantitative RT-PCR.
      (2) Isolated lung tissues were exposed to Fe(2+)/H(2)O(2) without or with
      different concentrations of NaHS (10(-5), 5 x 10(-5), 10(-4), 10(-3) mmol/L) at
      37 degree Celsius for 10 minutes, and the MDA content was assayed by biochemical
      method. RESULTS: (1) Compared with rats in control group, the concentration of
      plasma H(2)S and the activity of CSE in lung tissues in fibrosis group decreased
      on day 7 (all P<0.01); On the 28th day, the level of plasma H(2)S increased
      clearly (P<0.01) and the activity of CSE was ascendant without significant
      difference compared with that of control group. Relative CSE mRNA amounts in lung
      tissues increased 34%, 144%, respectively (all P<0.01) in rats of fibrosis group
      compared with those of control group. The contents of MDA and hydroxyproline
      increased significantly in fibrosis group compared with those of control group on
      days 7, 28 (all P<0.01). In NaHS-low group and NaHS-high group, the contents of
      MDA and hydroxyproline decreased markedly (all P<0.01). (2) The contents of MDA
      in incubation of lung tissues at different concentrations of NaHS were all
      decreased as compared with those in incubation with Fe(2+)/H(2)O(2) alone (all
      P<0.01). When NaHS was at 10(-4) mol/L, the MDA content reversed to the lowest
      value, which had the highest value at 10(-3) mol/L of NaHS. CONCLUSION:
      Endogenous CSE/H(2)S pathway was involved in the pathogenesis of rat pulmonary
      fibrosis. Exogenously applied H(2)S could attenuate the process of pulmonary
      fibrosis possibly because of reducing oxidative stress.

PMID- 16617355
TI  - [Survey of plasma lipid value in children in Beijing area and the changes of
      gaseous molecule-hydrogen sulfide in the ones with dyslipidemia].
AB  - OBJECTIVE: To evaluate plasma lipid value in children in Beijing areas and to
      explore the relationship between plasma hydrogen sulfide (H(2)S) level and lipid
      components. METHODS: A total of 971 healthy school students were chosen randomly,
      all coming from Beijing city and its counties. They were divided into four groups
      according to their gender and age (boys and girls in school age and in puberty).
      Body mass index (BMI) was calculated according to the measurement of body height
      and weight. Familial history, past medical history and the history of present
      illness were investigated. Physical examination was also carried on. Alanine
      aminotransferase (ALT), total cholesterol (TC), triglyceride (TG), high density
      lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C)
      were detected by HITACHI 7060 automatic biochemical analyzer. Forty children (31
      males and 9 females) with dyslipidemia were chosen randomly among them as
      patients. Other 60 children (38 males and 22 females) with normal plasma lipid
      level served as controls. Plasma H(2)S level was detected by modified sulfide
      electrode. RESULTS: There were 91 children with dyslipidemia (58 males and 33
      females) in 971 students. The prevalence rate was 9.37%. The average value of BMI
      in patients was higher than that of controls. An association of increased ALT
      level with the prevalence of dyslipidemia was observed. Hydrogen sulfide
      concentration in plasma showed out skew distribution. Measurement data were
      presented as median (P(25), P(75)). Hydrogen sulfide was 34.40 (32.98, 35.47)
      micromol/L in children with dyslipidemia and 38.81(36.53, 40.66) micromol/L in
      controls. There was statistical difference between the two groups (P<0.01).
      Average value of plasma hydrogen sulfide was 35.54 (33.41, 39.24) micromol/L in
      males and 37.82 (33.84, 39.80) micromol/L in females. There was no difference in
      plasma hydrogen sulfide between male and female subjects (P>0.05). CONCLUSION:
      The prevalence rate of dyslipidemia in Beijing children is relatively high as
      compared with what it was during the past several decades. There was a
      significant decrease in plasma endogenous H(2)S level in children with
      dyslipidemia as compared with that of healthy children. There was an obvious
      correlation between plasma hydrogen sulfide and plasma lipids.

PMID- 16617356
TI  - [Effect of adrenomedullin 1-50 on chronic hypoxic pulmonary hypertension in
      rats].
AB  - OBJECTIVE: To explore the effect of adrenomedullin(1-50) (ADM(1-50)) on hypoxic
      pulmonary hypertension and pulmonary vascular structural remodeling and the
      plasma concentration of nitric oxide (NO) and hydrogen sulfide (H(2)S) in rats.
      METHODS: Twenty male Wistar rats were randomly divided into control group (n=7),
      hypoxic group (n=6) and hypoxic with ADM(1-50) group (n=7). ADM(1-50) was
      subcutaneously administered into rats of hypoxic with ADM(1-50) group by mini
      osmotic pump (300 ng/h). After two weeks' hypoxic challenge, mean pulmonary
      arterial pressure (mPAP) was evaluated by using a right cardiac catheterization
      procedure. The ratio of right ventricular mass to left ventricular plus septal
      mass [RV/(LV+S)] was detected. Pulmonary vascular microstructure was measured and
      the ultrastructural changes in intra-acinar pulmonary arteries were observed.
      Meanwhile, plasma concentrations of NO and H(2)S were measured. RESULTS: mPAP was
      significantly increased in hypoxic rats than that in controls [(24.9+/-6.8) mmHg
      vs (14.3+/-2.4) mmHg, P<0.01,1 mmHg=0.133 kPa]; RV/(LV+S) was also significantly
      increased in hypoxic rats than that in controls [(0.318+/-0.054) vs (0.182+/
      0.007), P<0.01]. Microstructure and ultrastructure of pulmonary arteries changed
      obviously in hypoxic rats with the development of hypoxic pulmonary vascular
      structural remodeling. Meanwhile, plasma NO and H(2)S concentrations in hypoxic
      rats were markedly decreased compared with controls. However, mPAP was
      significantly decreased in hypoxic rats treated with ADM(1-50) than that in
      hypoxic rats [(14.9+/-3.0) mmHg vs (24.9+/-6.8) mmHg, P<0.01]; RV/(LV+S) was also
      significantly decreased than that in hypoxic rats [(0.185+/-0.011) vs (0.318+/
      0.054), P<0.01]. ADM(1-50) ameliorated pulmonary vascular structural remodeling
      of hypoxic rats in association with an increase in plasma NO and H(2)S
      concentrations. CONCLUSION: ADM(1-50) plays an important role in regulation of
      the development of hypoxic pulmonary hypertension and hypoxic pulmonary vascular
      structural remodeling, through promoting NO and H(2)S production in hypoxic rats.

PMID- 16617357
TI  - [Change and clinical implication of urotensin II in plasma and induced sputum of
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the roles of urotensin II (U-II) in chronic obstructive
      pulmonary disease (COPD). METHODS: Plasma and induced sputum were obtained from
      thirty four patients with stable COPD and ten healthy volunteers. The levels of U
      II in plasma and induced sputum were measured by RIA kit. Lung function was
      performed routinely. Induced sputum cells were counted with hemacytometer and
      differentiated with Wright-Giemsa stain. RESULTS: The levels of U-II in induced
      sputum were 82 and 65 folds higher than those of plasma U-II in COPD patients and
      healthy controls (P<0.01). The levels of U-II in plasma were unrelated to those
      of induced sputum (r = 0.168, P>0.05). No difference was noted between COPD and
      healthy controls in the plasma U-II levels [1.46(1.15, 1.73) vs 1.61(1.31, 2.17)
      microg/L, medians with interquartile ranges, P>0.05]. Sputum U-II levels from
      COPD patients were 15% higher than those of healthy controls [119.87(105.03,
      132.60) vs 104.44 (56.33, 122.24) microg/L, medians with interquartile ranges,
      P<0.05]. Induced sputum U-II levels of COPD patients had a trend of increase as
      lung function deteriorated and smoking index increases. Raised sputum total cell
      and neutrophil counts correlated strongly with the levels of U-II in induced
      sputum (r = 0.454, r = 0.431, both P<0.01). The levels of U-II in induced sputum
      correlated negatively with FEV(1)% predicted and p(O(2)) (r = -0.417, r = -0.518,
      both P<0.05). CONCLUSION: U-II may act locally, or, via paracrine or autocrine
      way, play a role in the mechanism of the airway inflammation and airway
      remodeling in COPD.

PMID- 16617358
TI  - [Effect of early exposure to allergen on rat asthmatic model].
AB  - OBJECTIVE: To investigate the effect of early exposure to allergen (ovalbumin,
      OVA) on rat asthmatic models. METHODS: Neonate rats were randomly divided into
      negative control group, asthmatic model group, low dose group and high dose
      group, with 8 in each. The rats of low dose group and high dose group were
      injected subcutaneously with 2 g/L OVA 0.1 mL and 10 g/L OVA 0.1 mL separately on
      the 1st day. OVA was given in asthmatic model group, low dose group and high dose
      group for allergization 6 weeks later and then asthmatic models were made. The
      pathologic changes of lung tissue, cell count and differentiation of
      bronchoalveolar lavage fluid (BALF) and serum interleukin-4 (IL-4), interferon
      gamma (IFN-gamma), OVA-specific IgE and OVA-specific IgG were observed. RESULTS:
      The airway inflammation in both low dose group and high dose group was less
      severe than that in asthmatic model group. Total cell count of BALF and the ratio
      of eosinophil and neutrophil of both groups were decreased significantly compared
      with asthmatic model group. IL-4 and OVA-specific IgE were markedly decreased,
      while IFN-gamma was significantly increased in both low dose group and high dose
      group compared with asthmatic model group respectively. There was no significant
      difference in IL-4, IFN-gamma and OVA-specific IgE between high dose group and
      control group. The serum OVA-specific IgG was elevated significantly in asthmatic
      model group, low dose group and high dose group compared with control group, and
      it was higher in high dose group than in asthmatic model group. CONCLUSION: Early
      exposure to OVA after birth could inhibit the airway inflammation and OVA
      specific IgE increasing induced by OVA in grown-up rats, and the mechanisms might
      be related to formation of immunology tolerance.

PMID- 16617359
TI  - [Effect of lidocaine on the impairment of learning and memory function and
      central cholinergic system after transient global cerebral ischemia in mice].
AB  - OBJECTIVE: To evaluate the effects of lidocaine on the impairments of learning
      and memorial function and central cholinergic system after transient global
      cerebral ischemia in mice of different apolipoprotein E genotypes. METHODS:
      Transient global ischemia was induced by bilateral common carotid arteries
      occlusion (BCCAO) for 17 minutes. Healthy male C57BL/6J wild-type mice (C57 mice)
      and apolipoprotein E knockout mice (ApoE mice) were randomly divided into six
      groups: C57 control group (sham operation, neither BCCAO was performed nor
      pharmacologic intervention was given), C57 ischemia group (BCCAO for 17 minutes
      was performed and normal saline was given intraperitoneally), C57 lidocaine group
      (BCCAO for 17 minutes was performed and lidocaine was given intraperitoneally),
      ApoE control group (the same procedure as that of C57 control group), ApoE
      ischemia group (the same procedure as that of C57 ischemia group), ApoE lidocaine
      group (the same procedure as that of C57 lidocaine group). The mice were allowed
      to recover for 7 days. Morris water maze test were performed from the 8th
      postoperative day. Mice were tested four times daily for 5 consecutive days. The
      latency periods were recorded and the percentages of effective search strategies
      were calculated. On the 12th postoperative day after Morris water maze test, mice
      were decapitated under anesthesia. The cerebral cortex and hippocampus were
      removed quickly. The activities of acetylcholinesterase (AChE) and choline
      acetyltransferase (ChAT) as well as the binding activity of muscarinic receptor
      (M receptor) were assayed. RESULTS: (1) The latency periods were significantly
      longer in the ischemia groups than in the corresponding control groups (P<0.05 or
      0.01). They were also significantly longer in C57 lidocaine group than in C57
      ischemia group [on the 3rd day of test, (74.1+/-32.7)s vs (49.2+/-19.5)s]
      (P<0.05). However, they were significantly shorter in apoE lidocaine group than
      in apoE ischemia group [from the 3rd to the 5th days of test, (40.7+/-27.7)s vs
      (84.7+/-26.8)s, (31.2+/-19.2)s vs (72.1+/-33.0)s, and (28.0+/-22.1)s vs (60.8+/
      26.9)s, respectively] (P<0.05 or 0.01). When compared between two strains, they
      were significantly longer in apoE ischemia group than in C57 ischemia group
      (P<0.05 or 0.01). However, they were significantly shorter in apoE lidocaine
      group than in C57 lidocaine group (P<0.01). (2) The percentages of effective
      search strategies were significantly lower in the ischemia groups than in the
      corresponding control groups (P<0.01). They were also significantly lower in C57
      lidocaine group than in C57 ischemia group [from the 3rd to the 5th days of test,
      (18.2+/-11.7)% vs (41.7+/-17.7)%, (22.7+/-20.8)% vs (55.6+/-20.8)%, and (29.6+/
      27.0)% vs (66.7+/-21.7)%, respectively] (P<0.01). However, they were
      significantly higher in apoE lidocaine group than in apoE ischemia group [from
      the 3rd to the 5th days of test, (41.7+/-25.8)% vs (15.6+/-12.9)%, 8.3+/-20.4)%
      vs (18.8+/-11.6)%, and (66.7+/-30.3)% vs (28.1+/-20.9)%, respectively] (P<0.01).
      When compared between two strains, they were significantly lower in apoE ischemia
      group than in C57 ischemia group (P<0.01). However, they were significantly
      higher in apoE lidocaine group than in C57 lidocaine group (P<0.01). (3) The
      parameters of central cholinergic system were significantly lower in the ischemia
      groups than in the corresponding control groups (P<0.05 or 0.01). They were also
      significantly lower in C57 lidocaine group than in C57 ischemia group [the
      activities of AChE of cerebral cortex and hippocampus, (0.44+/-0.09) U/mg protein
      vs (0.57+/-0.08) U/mg protein, and (0.73+/-0.21) U/mg protein vs (1.08+/-0.27)
      U/mg protein, respectively; the activities of ChAT of hippocampus, (80.60+/-6.55)
      pmol/mg protein/min vs (93.66+/-11.15) pmol/mg protein/min; and the binding
      activities of M receptor of cerebral cortex and hippocampus, (6.03+/-0.74)
      pmol/mg protein vs (7.49+/-0.48) pmol/mg protein, and (7.56+/-0.92) pmol/mg
      protein vs (10.65+/-3.35) pmol/mg protein, respectively] (P< 0.05 or 0.01).
      However, they were significantly higher in ApoE lidocaine group than in ApoE
      ischemia group [the activities of ChAT of cerebral cortex and hippocampus,
      (66.99+/-7.55) pmol/mg protein/min vs (46.23+/-4.96) pmol/mg protein/min, and
      (116.46+/-24.05) pmol/mg protein/min vs (92.08+/-16.33) pmol/mg protein/min,
      respectively] (P<0.05 or 0.01). When compared between two strains, they were
      significantly higher in ApoE lidocaine group than in C57 lidocaine group (P< 0.05
      or 0.01). CONCLUSION: Transient global cerebral ischemia caused significant brain
      damages in both strains of mice, which were represented by decline of learning
      and memorial function and damage of the central cholinergic system. Compared with
      the C57 mice, the ApoE mice had enhanced susceptibility to global cerebral
      ischemic injury as shown by more severe decline of the learning and memorial
      function. In the C57 mice, lidocaine significantly worsened the ischemic brain
      damage. In the ApoE mice, however, lidocaine significantly alleviated the
      ischemic cerebral results.

PMID- 16617360
TI  - [Effect of fenofibrate and metformin on lipotoxicity in OLETF rat kidney].
AB  - OBJECTIVE: To explore the possible molecular mechanism of abnormal renal lipid
      metabolism in OLETF rats, and the effects of fenofibrate or metformin on renal
      local lipid metabolism. METHODS: OLETF rats were randomly divided into three
      groups: one treated with fenofibrate, one with metformin and one without
      treatment. LETO rats were used as age-matched normal controls. The animals were
      sacrificed and the kidneys were obtained respectively at the age of 17 and 30
      weeks. 24-hour urine albumin contents and TG contents in renal cortex were
      measured.The levels of SREBP-1 protein and mRNA in kidney were measured. FAS mRNA
      and ACC mRNA expressions were measured with RT-PCR. RESULTS: OLETF rats showed
      characters of obesity, hyperglycemia, hyperlipidemia. At the end of thirty weeks
      clinical characters of renal damage appeared in OLETF rats, OLETF rats showed
      higher levels of 24-hour urine albumin contents than those of LETO rats. 24-hour
      urine albumin contents were correlated positively with TG contents in kidney. The
      partial correlation coefficient was 0.870 (P = 0.011) by controlling for body
      weight, serum lipid, blood glucose and fasting insulin concentration. OLETF rats
      showed higher levels of SREBP-1 protein (43.2%, P<0.01), FAS mRNA (126.0%,
      P<0.01), ACC mRNA (72.3%, P<0.01) than those of group LETO. OLETF/F rats showed
      lower levels of SREBP-1 (15.7%, P = 0.061), FAS mRNA (36.8%, P<0.05), ACC mRNA
      (40.3%, P<0.05) than those of group OLETF. OLETF/M rats showed lower levels of
      SREBP-1 (19.3%, P<0.01), FAS mRNA (57.3%, P<0.01), ACC mRNA (22.5%, P<0.05) than
      those of group OLETF. There was no difference in SREBP-1 mRNA levels for each
      group. CONCLUSION: Renal damage occurred in OLETF rats at the prediabetes stage.
      24-hour urine albumin contents were correlated positively with TG contents in
      kidney. SREBP-1 might aggravate fat deposition in kidney through some enzyme
      associated with fat synthesis, which was a possible pathogenesis of diabetic
      nephropathy. Treatment with fenofibrate or metformin ameliorated renal damage in
      OLETF rats through SREBP-1 and some enzyme regulated by it reduced fat deposit in
      kidney directly.

PMID- 16617361
TI  - Apoptosis of human hepatoma cell lines induced by transforming growth factor beta
      1 (TGF-beta1) correlates with p53 and Smad4 activation.
AB  - OBJECTIVE: To determine the relationships between apoptosis induced by
      transforming growth factor beta 1(TGF-beta1) and Smad in human hepatoma cell
      lines. METHODS: Three human hepatic carcinoma cell lines, involving different
      status of the p53 gene respectively, were used in this study. TGF-beta1-induced
      apoptosis in hepatic carcinoma cell lines was quantitated using the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. For
      identification of the mechanism of apoptosis induced by TGF-beta1, these cell
      lines were transfected with a TGF-beta1-inducible luciferase reporter plasmid
      containing Smad binding elements (SBE) and luciferase gene using LF2000, then
      were treated with TGF-beta1. Relative luciferase activity was assayed
      respectively. RESULTS: Among three cell lines studied with TUNEL assay, addition
      of TGF-beta1 induced apoptosis only in HepG2 cells (wild type p53). In contrast,
      Huh-7 (mutant p53) and Hep3B (deleted p53) cell lines lacked apoptosis. The
      detection of luciferase activity indicated that HepG2 cells dramatically
      increased the response to TGF-beta1 induction, Huh-7 and Hep3B cell lines
      significantly lowered luciferase expression. CONCLUSION: HepG2 cells were highly
      susceptible to TGF-beta1-induced apoptosis compared with Hep3B and Huh-7 cell
      lines. Smad4 may be a central mediator of the TGF-beta1 signaling transduction
      pathway.

PMID- 16617362
TI  - [Effect of hyperhomocysteinemia on cardiac remodeling in rats].
AB  - OBJECTIVE: To study the effects of hyperhomocysteinemia on cardiac remodeling and
      systolic function. METHODS: Twenty-four Wistar rats were divided randomly into
      experiment and control group. 12 rats of experiment group were bred with 1
      g/(kg.d) L-methionine. After 4 weeks, 6 of them were killed (HHcy), others were
      continuously bred with normal diet for 4 weeks (Quit hcy, QHcy). Twelve rats of
      control group with normal diet for 4 and 8 weeks. The plasma Hcy concentrations
      were measured by immuno-fluorescence technique. Left ventricular structure and
      systolic function were assessed by echocardiography. The cardiac morphology and
      collagen were studied by optical microscopy and image analysis system after
      hematoxylin eosin-staining and picrosirius red-staining. Immuno-histochemistry
      for actin-smooth muscle and factor VIII-related antigen was performed to identify
      changes in cardiac smaller arteriolar and microvascular numbers. RESULTS: The
      plasma Hcy concentration was (106.19+/-19.75) micromol/L in HHcy, (6.52+/-0.94)
      micromol/L in QHcy and (4.90+/-0.10) micromol/L in the control. Left ventricular
      systolic function was decreased 10.7% in HHcy. Left ventricular wall strain and
      cardiac smaller arteriolar wall thickness were increased by 62.1% and 2.9 fold in
      HHcy, 27.1% and 2.4 fold in QHcy as compared with the control. Cardiomyocyte
      diameter was not changed in HHcy and increased by 15.4% in QHcy as compared with
      the control. Microvascular number was decreased by 45.9% in HHcy as compared with
      the control, but smaller arteriolar number did not differ among the groups. Left
      ventricular systolic function and microvascular number resumed in QHcy.
      Interstitial and perivascular collagen deposition was significantly increased in
      HHcy and QHcy. CONCLUSION: Hyperhomocysteinemia may increase cardiomyocyte
      diameter, cardiac smaller arteriolar wall thickness and left ventricular wall
      strain; decrease microvascular number; induce interstitial and perivascular
      collagen deposition, directly and indirectly affect on cardiac remodeling and
      systolic function. The cardiac remodeling couldn't resume completely with plasma
      Hcy concentration being decreased.

PMID- 16617363
TI  - [Expression of epidermal growth factor receptor-2 in Chinese breast cancer
      patients: a meta-analysis].
AB  - OBJECTIVE: To study the expression of cerbB-2 and its clinical biology value in
      Chinese breast cancer patients by evidence based medical analysis. METHODS: All
      the published studies about cerbB-2 and breast cancer for the last 10 years were
      reviewed and standard techniques of meta-analysis to combined with the results of
      these studies were used to produce a more precise estimate of the prognostic
      significance expression of cerbB-2. RESULTS: The mean of cerbB-2 positive
      expression was 50% (95% confidence interval 48%-54%), cerbB-2 positive expression
      was related with node metastasis, recurrence after surgery and survival time; the
      RR values were 1.71, 2.14 and 2.32 respectively; tumor size, nuclear grade and
      pathology type were also the important factors that were related with the
      expression of cerbB-2, while the expression was not related with age; cerbB-2 was
      a special and sensitive prognostic factor for breast cancer. CONCLUSION: cerbB-2
      can be used as an independent molecular marker for definitive prognosis of breast
      cancer, as well as a reliable marker for choice of standard and individual
      therapy.

PMID- 16617364
TI  - [Helicobacter pylori genotypes of gastrointestinal B cell lymphoma].
AB  - OBJECTIVE: To assess the expression of specific virulence-associated Helicobacter
      pylori (Hp) genotypes. (cag A, vac A, and ice A status) in primary
      gastrointestinal B cell lymphoma. METHODS: Forty-nine paraffin wax embedded
      tissues were analyzed by immunohistochemical staining and polymerase chain
      reaction. RESULTS: There were 14 cases of mucosa associated lymphoid tissue
      lymphoma (MALT-L) (8 in stomach, and 6 in intestine) and 35 cases of diffuse
      large B cell lymphoma (DLBCL) (21 in stomach, and 14 in intestine) in all. The
      positive rates of vac A s1, vac A s2, vac A m2, ice A 1 and cag A were 50.0%,
      42.9%, 50.0%, 14.3% and 85.7% in MALT-L; 57.1%, 40.0%, 25.7%, 5.7% and 91.4% in
      DLBCL, respectively. CONCLUSION: High toxicity cag A+Hp strains seem to play a
      role in the pathogenesis of gastrointestinal B cell lymphoma, whereas vac A m2
      may be more associated with MALT-L. Clinical stage was not associated with
      virulence-associated Hp genotypes.

PMID- 16617365
TI  - [Ghrelin expression in the tissues of different thyroid diseases].
AB  - OBJECTIVE: To investigate whether ghrelin, a novel endogenous ligand of growth
      hormone secretagogue receptor (GHS-R), was expressed in the thyroid tissues of
      different thyroid diseases, and its implication. METHODS: The paraffin-embedded
      specimens of thyroid tissues from 2000 to 2004 were obtained from 57 patients
      with different thyroid diseases, including 5 subacute thyroiditis, 8 Hashimoto's
      thyroiditis, 7 hyperthyroidism (Graves disease), 8 nodular goiter, 5 thyroid
      adenoma, 3 thyroid lymphoma, 8 papillary carcinoma, 3 follicular carcinoma, 5
      medullary carcinoma and 5 undifferentiated carcinoma cases. The specimens of
      normal peri-adenoma thyroid tissues served as controls. Immunohistochemical
      staining was used to detect ghrelin expression. RESULTS: (1) ghrelin expression
      was undetectable in the thyroid tissues of normal control, subacute thyroiditis,
      Hashimoto's thyroiditis and Graves disease. (2) ghrelin expression was also
      undetected in the tissues of nodular goiter, thyroid adenoma and thyroid
      lymphoma. (3) ghrelin-positive staining was found in the tumor cells of different
      types of thyroid carcinoma. Five cases were positive within 8 cases in papillary
      carcinoma, 2 cases were positive within 3 cases in follicular carcinoma, 3 cases
      were positive within 5 cases in medullary carcinoma, 3 cases were positive within
      5 cases in undifferentiated carcinoma. CONCLUSION: Ghrelin is expressed in
      malignant epithelial thyroid neoplasms, but not in autoimmune or inflammatory
      thyroid diseases and benign nodular thyroid diseases. The results indicate that
      ghrelin expression may play an important role in the occurrence and development
      of thyroid carcinoma.

PMID- 16617366
TI  - [Effect of soy isoflavone on gene expression of leptin and insulin sensibility in
      insulin-resistant rats].
AB  - OBJECTIVE: To explore the effects of soy isoflavone (SIF) on gene expression of
      leptin and insulin sensibility in insulin-resistant (IR) rats induced by high
      fat, and to reveal the mechanisms of SIF in ameliorating insulin sensibility.
      METHODS: IR rats were randomly divided into four groups based on their insulin
      resistant indexes (IRI): one model control group and three SIF groups that were
      gavaged with water solutions with SIF at doses of 0 mg/kg, 50 mg/kg, 150 mg/kg,
      and 450 mg/kg, respectively. After one month, fasting glucose, fasting insulin,
      leptin in serum, and leptin mRNA in the perirenal adipocyte were detected by
      enzymic method, radioimmunoassay, enzyme linked immunosorbent assay, and real
      time quantitative RT-PCR, respectively. RESULTS: The model control group was used
      to compare against the other groups: (1) Insulin and IRI were lower in the 150
      mg/kg and 450 mg/kg groups; (2) In the 450 mg/kg group, body weight and leptin
      mRNA expression were lower, serum leptin content was higher. CONCLUSION: These
      results indicate that soy isoflavone might decrease body weight of rats and
      leptin mRNA, increase serum leptin level, and ameliorate leptin and insulin
      sensitivities.

PMID- 16617367
TI  - [A three-year clinical evaluation of galvano-ceramic bridges made by Ni-Cr pontic
      bonding galvano caps].
AB  - OBJECTIVE: To evaluate the clinical effect of galvano-ceramic bridges made by Ni
      Cr pontic fired bonding galvano caps with highly temperature-resistant adhesive
      based on three-year clinical trials. METHODS: A total of 29 galvano-ceramic
      bridges made by Ni-Cr pontic fired bonding on the galvano caps were used for 26
      patients. Abutment teeth plaque indices (PI) were compared according to Silness
      and Loe standards and their papillary bleeding indices (PBI) according to Mazza
      standards before restoration and after 36 months' restoration. At the same time,
      the integrity and marginal fitness of galvano-ceramic bridges were observed.
      RESULTS: The PBI at abutment teeth were higher than those before restoration,
      Wilcoxon test revealed significant difference. Their PI were lower than those
      before restoration, Wilcoxon test revealed significant difference. All the
      galvano-ceramic bridges were perfect in marginal fitness and color. The rate of
      integrity was 89.7% in the period of observation. CONCLUSION: Galvano-ceramic
      bridges made by Ni-Cr pontic fired bonding galvano caps with highly temperature
      resistant adhesive hold out good prospects for clinical use in fixed restoration.

PMID- 16617368
TI  - [Effect of acid etching time on bonding interface of non-carious cervical
      sclerotic dentin].
AB  - OBJECTIVE: To examine the effect of acid etching time on the bonding interface of
      non-carious cervical sclerotic dentin. METHODS: Twenty extracted premolars with
      non-carious cervical lesions were randomly divided into two groups, the lesion
      surface was conditioned with Scotchbond Multi-Purpose Plus dentin bonding system.
      The etching time was 15 s and 30 s respectively. The bonding interface
      ultrastructures were compared with SEM. RESULTS: In sclerotic dentin (15 s), the
      hybrid layer was visible, with minimal resin tags in the dentinal tubules and,
      when presented, they were shorter. Doubling the etching time (30 s) resulted in
      more resin tags with an hybrid layer formation on peritubular dentin. CONCLUSION:
      Doubling the etching time improved the ultrastructure of sclerotic dentin-resin
      bonding interface, and could be an efficient way to improve the bonding effect.

PMID- 16617369
TI  - [Enhanced-real time PCR: a highly sensitive method for SARS-coronavirus
      detection].
AB  - An enhanced real-time polymerase chain reaction (ERT-PCR) assay to detect the
      coronavirus associated with severe acute respiratory syndrome (SARS-Cov) has been
      designed for detection of SARS-Cov with high sensitivity and easy-to-interpret
      results, in which a target gene pre-amplification step preceded TaqMan real-time
      fluorescent PCR. The limit of detection of the ERT-PCR method was 10(-2) higher
      than the standard real-time PCR assay and 10(-7) higher than conventional PCR
      methods. The increased sensitivity of the assay would have major benefits in
      screening suspected SARS patients rapidly and efficiently and may help control
      the spread of SARS and other infectious diseases during future outbreak.

PMID- 16617370
TI  - [Study of the inborn errors of mitochondrial fatty acid beta-oxidation
      deficiency].
AB  - Mitochondrial fatty acids beta-oxidation is a repetitive process of four steps
      which provides the major source of energy for heart, liver and skeletal muscle.
      Several enzymes are involved in this spiral cycle. The medium-chain acyl-CoA
      dehydrogenase (MCAD), the short-chain acyl-CoA dehydrogenase (SCAD), the long
      chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) and the carnitine-palmitoyl-CoA
      transferase II (CPT II) deficiency have been recognized as the most common inborn
      errors of metabolism and frequently reported in their association with sudden
      infant death (SID). The prevalent mutations in these genes need further
      investigation in different populations.

PMID- 16617371
TI  - [caCORE: core architecture of bioinformation on cancer research in America].
AB  - A critical factor in the advancement of biomedical research is the ease with
      which data can be integrated, redistributed and analyzed both within and across
      domains. This paper summarizes the Biomedical Information Core Infrastructure
      built by National Cancer Institute Center for Bioinformatics in America (NCICB).
      The main product from the Core Infrastructure is caCORE--cancer Common Ontologic
      Reference Environment, which is the infrastructure backbone supporting data
      management and application development at NCICB. The paper explains the structure
      and function of caCORE: (1) Enterprise Vocabulary Services (EVS). They provide
      controlled vocabulary, dictionary and thesaurus services, and EVS produces the
      NCI Thesaurus and the NCI Metathesaurus; (2) The Cancer Data Standards Repository
      (caDSR). It provides a metadata registry for common data elements. (3) Cancer
      Bioinformatics Infrastructure Objects (caBIO). They provide Java, Simple Object
      Access Protocol and HTTP-XML application programming interfaces. The vision for
      caCORE is to provide a common data management framework that will support the
      consistency, clarity, and comparability of biomedical research data and
      information. In addition to providing facilities for data management and
      redistribution, caCORE helps solve problems of data integration. All NCICB
      developed caCORE components are distributed under open-source licenses that
      support unrestricted usage by both non-profit and commercial entities, and caCORE
      has laid the foundation for a number of scientific and clinical applications.
      Based on it, the paper expounds caCORE-base applications simply in several NCI
      projects, of which one is CMAP (Cancer Molecular Analysis Project), and the other
      is caBIG (Cancer Biomedical Informatics Grid). In the end, the paper also gives
      good prospects of caCORE, and while caCORE was born out of the needs of the
      cancer research community, it is intended to serve as a general resource. Cancer
      research has historically contributed to many areas beyond tumor biology. At the
      same time, the paper makes some suggestions about the study at the present time
      on biomedical informatics in China.

PMID- 16617372
TI  - Global patterns in human mitochondrial DNA and Y-chromosome variation caused by
      spatial instability of the local cultural processes.
AB  - Because of the widespread phenomenon of patrilocality, it is hypothesized that Y
      chromosome variants tend to be more localized geographically than those of
      mitochondrial DNA (mtDNA). Empirical evidence confirmatory to this hypothesis was
      subsequently provided among certain patrilocal and matrilocal groups of Thailand,
      which conforms to the isolation by distance mode of gene diffusion. However, we
      expect intuitively that the patterns of genetic variability may not be consistent
      with the above hypothesis among populations with different social norms governing
      the institution of marriage, particularly among those that adhere to strict
      endogamy rules. We test the universality of this hypothesis by analyzing Y
      chromosome and mtDNA data in three different sets of Indian populations that
      follow endogamy rules to varying degrees. Our analysis of the Indian patrilocal
      and the matrilocal groups is not confirmatory to the sex-specific variation
      observed among the tribes of Thailand. Our results indicate spatial instability
      of the impact of different cultural processes on the genetic variability,
      resulting in the lack of universality of the hypothesized pattern of greater Y
      chromosome variation when compared to that of mtDNA among the patrilocal
      populations.

PMID- 16617373
TI  - A novel bacterium associated with lymphadenitis in a patient with chronic
      granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte
      NADPH oxidase system causing defective production of toxic oxygen metabolites,
      impaired bacterial and fungal killing, and recurrent life-threatening infections.
      We identified a novel gram-negative rod in excised lymph nodes from a patient
      with CGD. Gram-negative rods grew on charcoal-yeast extract, but conventional
      tests could not identify it. The best 50 matches of the 16S rRNA (using BLAST)
      were all members of the family Acetobacteraceae, with the closest match being
      Gluconobacter sacchari. Patient serum showed specific band recognition in whole
      lysate immunoblot. We used mouse models of CGD to determine whether this organism
      was a genuine CGD pathogen. Intraperitoneal injection of gp91(phox -/-) (X
      linked) and p47 (phox -/-) (autosomal recessive) mice with this bacterium led to
      larger burdens of organism recovered from knockout compared with wild-type mice.
      Knockout mouse lymph nodes had histopathology that was similar to that seen in
      our patient. We recovered organisms with 16S rRNA sequence identical to the
      patient's original isolate from the infected mice. We identified a novel gram
      negative rod from a patient with CGD. To confirm its pathogenicity, we
      demonstrated specific immune reaction by high titer antibody, showed that it was
      able to cause similar disease when introduced into CGD, but not wild-type mice,
      and we recovered the same organism from pathologic lesions in these mice.
      Therefore, we have fulfilled Koch's postulates for a new pathogen. This is the
      first reported case of invasive human disease caused by any of the
      Acetobacteraceae. Polyphasic taxonomic analysis shows this organism to be a new
      genus and species for which we propose the name Granulobacter bethesdensis.

PMID- 16617375
TI  - The MogR transcriptional repressor regulates nonhierarchal expression of
      flagellar motility genes and virulence in Listeria monocytogenes.
AB  - Flagella are surface structures critical for motility and virulence of many
      bacterial species. In Listeria monocytogenes, MogR tightly represses expression
      of flagellin (FlaA) during extracellular growth at 37 degrees C and during
      intracellular infection. MogR is also required for full virulence in a murine
      model of infection. Using in vitro and in vivo infection models, we determined
      that the severe virulence defect of MogR-negative bacteria is due to
      overexpression of FlaA. Specifically, overproduction of FlaA in MogR-negative
      bacteria caused pleiotropic defects in bacterial division (chaining phenotype),
      intracellular spread, and virulence in mice. DNA binding and microarray analyses
      revealed that MogR represses transcription of all known flagellar motility genes
      by binding directly to a minimum of two TTTT-N5-AAAA recognition sites positioned
      within promoter regions such that RNA polymerase binding is occluded. Analysis of
      MogR protein levels demonstrated that modulation of MogR repression activity
      confers the temperature-specificity to flagellar motility gene expression.
      Epistasis analysis revealed that MogR repression of transcription is antagonized
      in a temperature-dependent manner by the DegU response regulator and that DegU
      further regulates FlaA levels through a posttranscriptional mechanism. These
      studies provide the first known example to our knowledge of a transcriptional
      repressor functioning as a master regulator controlling nonhierarchal expression
      of flagellar motility genes.

PMID- 16617376
TI  - Folding very short peptides using molecular dynamics.
AB  - Peptides often have conformational preferences. We simulated 133 peptide 8-mer
      fragments from six different proteins, sampled by replica-exchange molecular
      dynamics using Amber7 with a GB/SA (generalized-Born/solvent-accessible
      electrostatic approximation to water) implicit solvent. We found that 85 of the
      peptides have no preferred structure, while 48 of them converge to a preferred
      structure. In 85% of the converged cases (41 peptides), the structures found by
      the simulations bear some resemblance to their native structures, based on a
      coarse-grained backbone description. In particular, all seven of the beta
      hairpins in the native structures contain a fragment in the turn that is highly
      structured. In the eight cases where the bioinformatics-based I-sites library
      picks out native-like structures, the present simulations are largely in
      agreement. Such physics-based modeling may be useful for identifying early nuclei
      in folding kinetics and for assisting in protein-structure prediction methods
      that utilize the assembly of peptide fragments.

PMID- 16617377
TI  - Prions adhere to soil minerals and remain infectious.
AB  - An unidentified environmental reservoir of infectivity contributes to the natural
      transmission of prion diseases (transmissible spongiform encephalopathies [TSEs])
      in sheep, deer, and elk. Prion infectivity may enter soil environments via
      shedding from diseased animals and decomposition of infected carcasses. Burial of
      TSE-infected cattle, sheep, and deer as a means of disposal has resulted in
      unintentional introduction of prions into subsurface environments. We examined
      the potential for soil to serve as a TSE reservoir by studying the interaction of
      the disease-associated prion protein (PrP(Sc)) with common soil minerals. In this
      study, we demonstrated substantial PrP(Sc) adsorption to two clay minerals,
      quartz, and four whole soil samples. We quantified the PrP(Sc)-binding capacities
      of each mineral. Furthermore, we observed that PrP(Sc) desorbed from
      montmorillonite clay was cleaved at an N-terminal site and the interaction
      between PrP(Sc) and Mte was strong, making desorption of the protein difficult.
      Despite cleavage and avid binding, PrP(Sc) bound to Mte remained infectious.
      Results from our study suggest that PrP(Sc) released into soil environments may
      be preserved in a bioavailable form, perpetuating prion disease epizootics and
      exposing other species to the infectious agent.

PMID- 16617378
TI  - [The role of chemical and physical factors in cancer development].
AB  - The author deals with the effects of environmental chemical-, and physical
      carcinogens playing predominant role in nearly 90% of the cancer development.
      Different steps of chemical carcinogenesis, classification and evaluation of
      carcinogens according to the criteria of International Agency for Research on
      Cancer, and the most important biological markers of genotoxic exposures are
      presented. Among physical agents the carcinogenic effects of ionizing and
      nonionizing radiations are demonstrated, including limited, inadequate or proved
      carcinogenic action of UV, microwave, static and low-frequency electric and
      magnetic fields.

PMID- 16617379
TI  - [The feasibility and the role of sentinel lymph node biopsy after neoadjuvant
      chemotherapy in breast cancer].
AB  - INTRODUCTION AND AIMS: The feasibility, accuracy and clinical significance of
      sentinel lymph node biopsy for patients with breast cancer after neoadjuvant
      chemotherapy has not yet been determined. The aim of this study was to
      investigate these questions. PATIENTS AND METHOD: Dual agent-guided sentinel
      lymph node biopsy with preoperative lymphoscintigraphy was performed on 17 breast
      cancer patients after neoadjuvant chemotherapy at the Department of General and
      Thoracic Surgery, National Institute of Oncology, Budapest, from April 2004 to
      August 2005. Patients with clinically lymph node-negative breast cancer less than
      3 cm in size after neoadjuvant chemotherapy were enrolled in the study. RESULTS:
      Lymphoscintigraphy showed no axillary lymphatic drainage in 7 patients (41%), and
      no sentinel lymph node could be identified during surgery in these patients.
      Axillary lymph nodes were histologically positive in 6 (86%) out of these 7
      patients. Sentinel lymph node biopsy was successful in 10 patients (59%), and in
      8 (80%) of them the sentinel lymph node proved to be positive pathologically.
      False negative sentinel lymph node biopsy did not occur. Axillary lymph node
      status was histologically positive in 14 (82%) out of the 17 patients. The
      predictable value of the clinical examination of the axilla after neoadjuvant
      chemotherapy, for the histological nodal status, was very low. DISCUSSION AND
      CONCLUSIONS: Our sentinel lymph node identification rate is lower than the
      published average in the literature. This difference can be explained by the
      differences in the indication for neoadjuvant chemotherapy. Our false negative
      rate (0%) is, however, significantly better than that of others. On the basis of
      international experiences sentinel lymph node biopsy after neoadjuvant
      chemotherapy is technically feasible, but its accuracy is not satisfactory and
      its clinical significance has not yet been determined. Our success rate is
      specifically low, which cannot be explained by the lack of practice. Taking the
      histologically very high axillary positive rate into consideration, sentinel
      lymph node biopsy has no clinical role in our practice after neoadjuvant
      chemotherapy.

PMID- 16617380
TI  - [Subacute cardiotoxicity caused by anthracycline therapy in children: can
      dexrazoxane prevent this effect?].
AB  - OBJECTIVES: The use of anthracyclines are limited by their cardiotoxic side
      effects (first of all congestive cardiomyopathy). In this study we analyzed the
      anthracycline-induced cardiotoxicity and the possible preventive role of
      dexrazoxane in children. PATIENTS: 158 anthracycline-treated long-term survivors
      could be analyzed. Sixty-one children received dexrazoxane (group D) and 97
      patients received anthracyclines only (group C). METHODS: Cardiac ultrasound
      examinations (ECHO) and electrocardiograms (ECG) were performed regularly from
      the beginning of chemotherapy and yearly thereafter. Shortening fraction (FS) was
      used as indicator of the ventricular function. RESULTS: The incidence of reduced
      left ventricular function (FS) was 13.4% in C, and 8.2% in D (p=ns). Two years
      after completion of the chemotherapy FS was reduced in 13.7% in C and 0% in D,
      respectively (p=0.056), and 5 years after therapy in 11.0% in C and 2.4% in D,
      respectively (P=0.034). Left chamber wall diameter was abnormal in systole in 6%
      in C and 2% in D, in diastole in 11% in C and 7% in D (p=ns) after 3 years of
      follow-up. CONCLUSION: Anthracycline-induced subacute cardiotoxicity can be
      significantly diminished by the concomitant use of dexrazoxane. For the final
      conclusions longer follow-up is necessary.

PMID- 16617381
TI  - [Thymidylate synthase gene promoter polymorphism in patients with advanced head
      and neck cancer treated by radio- and 5-fluorouracil chemotherapy].
AB  - AIM: Thymidylate synthase (TS) is a rate-limiting enzyme in the DNA synthetic
      pathway, and represents a cellular target of antimetabolite drug 5-fluorouracil.
      It catalyzes the reductive methylation of deoxyuridine-5'-monophosphate to
      deoxythymidine-5'-monophosphate. Inhibition of TS will result in depletion of
      both dTMP and, subsequently, dTTP. As a consequence, dUTP is misincorporated into
      DNA, resulting in DNA breakage and cell death. Developing resistance against 5
      fluorouracil (FURA) based drugs might be due to the failure of inhibition of
      thymidylate synthase enzyme function. In the promoter region of the TS gene there
      is a tandem repeat sequence (2R or 3R), which was found to be polymorphic and
      influences the gene expression. Effectiveness and tolerability of Tegafur
      treatment might be influenced by expression of the TS gene. Our purpose was to
      determine the effectiveness and tolerability of concomitant radiotherapy and low
      dose chemotherapy using Tegafur in respect of promoter polymorphism of
      thymidilate synthase gene. MATERIAL AND METHODS: TS promoter polymorphism (2R/2R,
      2R/3R, 3R/3R) was determined by polymerase chain reaction using genomic DNA, in
      47 patients with advanced head and neck cancer. RESULTS: Thirty patients out of
      47 showed complete response, and genotyping of these patients revealed 2R/2R in
      22 (73.3%), 2R/3R in 2 (6.7%) and 3R/3R in 6 (20%). Seventeen out of 47 patients
      reacted with partial response, and 2R/2R or 2R/3R were revealed in 5 (29.4%) and
      3 (17.6%) patients, respectively, and 3R/3R genotype was identified in 9 patients
      (53%). CONCLUSION: We did not find any correlation between patient's data and
      response to therapy, but strong correlation was found between the latter and the
      patient's genotype. This facts indicate that the analysis of promoter
      polymorphism of thymidylate synthase gene might be a useful target to examine
      before FURA-based chemotherapy, and might allow to go into the direction of
      individualized treatment of head and neck cancer. We suppose that tumor response
      depends on genomic features of the patients.

PMID- 16617374
TI  - New perspectives on host-parasite interplay by comparative transcriptomic and
      proteomic analyses of Schistosoma japonicum.
AB  - Schistosomiasis remains a serious public health problem with an estimated 200
      million people infected in 76 countries. Here we isolated ~ 8,400 potential
      protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa
      84,000 expressed sequence tags. In tandem, we undertook a high-throughput
      proteomics approach to characterize the protein expression profiles of a number
      of developmental stages (cercariae, hepatic schistosomula, female and male
      adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell
      and tegument) by interrogating the protein database deduced from the contigs.
      Comparative analysis of these transcriptomic and proteomic data, the latter
      including 3,260 proteins with putative identities, revealed differential
      expression of genes among the various developmental stages and sexes of S.
      japonicum and localization of putative secretory and membrane antigens, enzymes,
      and other gene products on the adult tegument and eggshell, many of which
      displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high
      levels of identity with those of their mammalian hosts, whereas many others
      appeared to be conserved only across the genus Schistosoma or Phylum
      Platyhelminthes. These findings are expected to provide new insights into the
      pathophysiology of schistosomiasis and for the development of improved
      interventions for disease control and will facilitate a more fundamental
      understanding of schistosome biology, evolution, and the host-parasite interplay.

PMID- 16617382
TI  - [Significance of endoscopic biopsy and cytology in the diagnosis of esophageal
      squamous cell carcinoma].
AB  - We have tested the role and significance of histology combined with cytology in
      the diagnosis of esophageal squamous cell carcinomas. Biopsy specimens and
      samples for cytological smear were taken by a fiberoptic flexible endoscope. In
      order to minimise the loss of biological sample, the residue from the brush was
      removed with rinsing fluid. From 1973 to 2005 we examined 820 patients with
      squamous cell carcinoma of the esophagus. Endoscopic biopsy yielded positive
      result in 97.2%. Cytology performed in 724 patients turned out to be positive in
      90.3%. Both examinations were conducted in 648 patients (79%), and yielded
      positive result in 572 patients (88.3%). Negative biopsy result was obtained in
      22 patients, however, 14 of them had positive cytological diagnosis. Both biopsy
      and cytology were negative in 8 cancer patients (1%). No complication was
      observed with either diagnostic technique. In our material cancer was diagnosed
      in 776 patients by histology. However, in a further 14 of 22 patients with
      negative histology, cancer was detected by cytology. This means that the presence
      of cancer was also confirmed on the basis of morphological features in 790 cases,
      i.e. in 96.3% of the patients. Our results show that the combined use of biopsy
      and cytology in malignant tumours yields high diagnostic accuracy. Since abrasion
      exfoliate cytology is a quick and useful diagnostic measure it should be a
      routine examination in the evaluation of abnormal changes in the esophageal
      mucosa. The examination of the rinsing fluid of the sampling brush, introduced by
      us, yielded additional diagnostic information.

PMID- 16617383
TI  - [First observations of the dose-dense weekly docetaxel therapy in relapsed
      ovarian cancer].
AB  - Weekly docetaxel therapy is a new therapeutical form of relapsed ovarian cancer.
      Phase I and II trials of this administration form are rare in the literature of
      this tumor type. The authors report on a retrospective study of this treatment.
      MATERIALS AND METHODS: Ten patients with recurrent epithelial ovarian carcinoma
      were treated by dose-dense weekly docetaxel in 57 courses. The patients received
      a median of 6 courses of docetaxel on day 1, 8 and 15 together with a one-week
      pause, in 4-week courses. The average age of the patients was 61+/-9 years. Eight
      patients received a docetaxel monotherapy at a dose of 40 mg/m2, in weekly
      administration, and two patients weekly docetaxel combination therapy with
      carboplatin of AUC 3, on the same days as above. The premedication used before
      docetaxel was the same as the one given in the 3-week protocols: the patients
      received treatments of 100 mg methyl-prednisolone 12 hours and half an hour
      before docetaxel infusion. No G4 hematological toxicities were observed. G3 and
      G2 leucopenia was found in 6/57=11% and 4/57=8% of treatments. No granulocyte
      colony stimulating factor was given. Progression-free interval (PFI) was
      calculated by GraphPad Prism (version 2.0) program. RESULTS: Complete response
      was found in two patients (2/10=20%), and the patients are tumor-free 2 and 3
      months after treatment. All the other patients showed tumor progression after
      some time of stabilization. The median progression-free interval was calculated
      as 2 months. CONCLUSION: Weekly docetaxel is found to be a tolerable treatment
      form of relapsed ovarian cancer patients. For the evaluation of the treatment
      more studies are warranted.

PMID- 16617384
TI  - [Prognostic role of microvascularization in surgically treated lung cancer].
AB  - OBJECTIVE: The aim of our study was the determination of microvascularization and
      its prognostic significance in lung cancer patients. METHODS: Histological
      sections were prepared from paraffin-embedded tissues removed from the peripheral
      part of the tumor of 450 radically operated non-small cell and small cell lung
      cancer patients. Immunohistochemical staining was performed with antibody against
      factor VIII-associated antigen. During computer imaging, the absolute and
      relative parameters of vascularization were determined, as was the density of
      tumor cells situated to the nearest neighboring vessels. The results were
      compared with TNM status, the cell type and survival. RESULTS: T2 and T4 tumors
      demonstrated an enhanced vascularization, however, except for the surface
      fraction, statistically significant difference was not found. The
      microvascularization parameters did not differ significantly between tumors with
      different N status. In small cell lung cancer cases, the vascularization was
      stronger than in non-small cell lung cancer cases, while cell density was lower,
      however, these differences did not prove statistically significant. The survival
      rate decreased significantly with the increasing tumor cell density in the
      interval of 0-20 microm. CONCLUSIONS: A clear connection could not be
      demonstrated between vascularization and the appearance of lymph node metastases.
      The density of tumor cells measured in the direct vicinity of vessels proved an
      important prognostic factor.

PMID- 16617386
TI  - Some of the statements of the International Committee on Nuclear Technology (ILK)
      about the impacts of the Chernobyl accident after twenty years.

PMID- 16617385
TI  - [Gliomatosis cerebri].
AB  - A 64 years old woman presented with weakness, vertigo, paresthesia, dementia,
      which progressed to coma in a three-month-long period. The autopsy revealed
      pulmonary thrombosis and infarction, gastric erosions, peptic ulcer in the
      duodenum, leiomyoma in the esophagus, fibrosis of the pancreas and mild
      atherosclerosis. On macroscopic examination, the 1440 g brain did not show any
      bleeding, infarction or tumor. The histologic examination revealed gliomatosis
      cerebri of the white matter of the cerebral hemispheres.

PMID- 16617387
TI  - Current application of sentinel lymph node lymphoscintigraphy to detect various
      cancer metastases.
AB  - In this review article, the application of sentinel lymph node (SLN)
      lymphoscintigraphy not only in breast cancer and melanoma but also in cancers of
      the genital organs and the lungs is described. After a brief historical
      background, including Virchow and Cabanas' views, a description of the basic
      technique and the sensitivity and specificity of this technique in identifying
      SLN in breast cancer and melanoma are presented. In cervical and vulvar cancer
      and also in lung cancer, special techniques are applied before and during surgery
      and evaluated after surgical operation. The advantages and disadvantages of using
      SLN lymphoscintigraphy are described. Finally, our experience from using SLN
      lymphoscintigraphy, especially in cervical cancer, is presented. The technique
      for SLN mapping may save the patient from extended surgical procedures, indicate
      the pathways of lymph drainage and identify skip metastases. Nevertheless, the
      sensitivity of this technique should improve more in order to provide information
      concerning the extent of surgical treatment.

PMID- 16617388
TI  - Quantitative studies using positron emission tomography (PET) for the diagnosis
      and therapy planning of oncological patients.
AB  - Positron emission tomography (PET) has found wide-spread use in oncology due to
      the relatively high accuracy in the staging, differential diagnosis and therapy
      monitoring. Most PET studies are performed as a whole body scan. In selected
      cases a semiquantitative analysis is performed, which is based on the calculation
      of standardized uptake values (SUV). The present studies were undertaken in order
      to evaluate the impact of dynamic PET studies in malignant diseases with respect
      to tumor diagnosis and therapy management. Dynamic data acquisition is superior
      to static images because is provides information about the tracer distribution
      with respect of time and space, in a region of interest. The impact of different
      compartmental and non-compartmental approaches for the diagnostics and therapy
      planning was also studied. The radiopharmaceuticals used for patient studies
      were: O-15-water, C-11-ethanol, F-18-fluorodeoxyglucose (FDG), F-18-fluorouracil
      (F-18-FU), and 6-F-18-fluoro-L-DOPA. A new evaluation strategy of dynamic PET
      studies based on an integrated evaluation including both compartment and non
      compartment models as well as the use of SUV is presented. Furthermore, the
      parametric imaging including Fourier-analysis and regressions analysis was used.
      RESULTS: PET-studies with labeled cytostatic agents provide informations about
      the transport and elimination of a cytostatic agent and help to predict the
      therapeutic outcome. The retention of the radiolabeled cytostatic agent F-18-FU
      in liver metastases of colorectal cancer was low after systemic application.
      Lesions with retention values >3.0 SUV and with <2.0 SUV correlated with negative
      and positive growth rates, respectively. A high F-18-FU retention (>2.96 SUV) was
      associated with longer survival times (>21 months). In contrast, patients with
      lower F-18-FU retention values (<1.2 SUV) survived no longer than one year. A
      higher diagnostic accuracy was obtained by using an integrated evaluation
      including both compartment and non-compartment models. (18)F-FDG studies for the
      diagnosis of soft tissue sarcomas showed a sensitivity and specificity of 91% and
      88% for the primary tumors and 88% and 92% for the recurrences, respectively.
      Using a combination of SUV and transport rates, it was possible to further
      classify malignant soft tissue tumors with regard to tumor grading percentages of
      84% of the G III, 37.5% of the G II, 80% of the G I tumors, as well as 50% of the
      lipomas and 14.3% of scar tissue were correctly classified using the integrated
      evaluation. In patients with bone tumors, integrated evaluation was also superior
      to SUV or visual evaluation leading to a sensitivity of 76% (for SUV: 54%), a
      specificity of 97% (for SUV: 91%) and an accuracy of 88% (for SUV: 75%). The
      diagnostic efficacy of SUV and of the fractal dimension of the time activity data
      of FDG was evaluated in 159 patients with 200 lesions of different tumors with
      respect to differential diagnosis and the prognosis of therapeutic outcome.
      Discriminant analysis revealed a diagnostic accuracy of 76.65% for all patients,
      67.7% for the untreated group of patients and 83.44% for the pretreated patients.
      The advantage of parametric imaging is the visualization of one isolated
      parameter of the tracer s kinetic, like the phosphorylation in case of (18)F-FDG.
      Furthermore, the delineation of a tumor is better due to the absence of
      background activity. The presented data also demonstrate that parametric imaging
      based on Fourier transformation may be useful for the evaluation of the
      pharmacokinetics and effectiveness of regional therapeutic procedures. In
      conclusion, a semiquantitative analysis of PET data sets based on SUV is in
      general helpful and should be performed under standardized conditions, concerning
      the time after tracer application, the blood glucose level in case of (18)F-FDG,
      partial volume correction and the choice of reconstruction parameters. The
      combination of two SUV s, an early and a late one is a simple and usefull
      approach for the evaluation of a dynamic series in a clinical environment. PET
      studies with labeled cytostatic agents provide information about the transport
      and elimination of a cytostatic agent and help to predict the therapeutic
      outcome. Non-compartment models require further evaluation.

PMID- 16617389
TI  - Zinc as an antiperoxidative agent following iodine-131 induced changes on the
      antioxidant system and on the morphology of red blood cells in rats.
AB  - Iodine-131 ((131)I) irradiation is the first line treatment for Graves' disease
      and thyroid carcinoma. In such cases, (131)I gets accumulated in the thyroid, and
      is released in the form of radioiodinated triiodothyronine (T3) and
      tetraiodothronine (T4). Various reports describe changes in the blood picture
      after radioiodine treatment. Zinc, on the other hand, has been reported to
      maintain the integrity of red blood cells (RBC) under certain toxic conditions.
      The present study was conducted to evaluate the adverse effects of (131)I on the
      antioxidant defense system and morphology of RBC and also to assess the possible
      protection by zinc under irradiation by (131)I. Thirty two female Wistar rats
      were equally segregated into four main groups. Animals with Group I served as
      normal controls; Group II animals were administered a dose of 3.7 MBq of (131)I
      (carrier free) intraperitoneally, Group III rats were supplemented with zinc (227
      mg/L drinking water) and Group IV rats were given a combined treatment of (131)I
      and zinc, in a similar way as in Group II and IV rats. After seven days of (131)I
      treatment, RBC lysate was prepared and its antioxidant status assessed. The
      activity of superoxide dismutase (SOD), reduced glutathione (GSH) and
      malondialdehyde (MDA) in the lysate of RBC was increased. On the contrary, the
      activity of catalase was found to be significantly decreased. The activity of
      glutathione reductase (GR) remained unchanged. Marked changes in the shape of RBC
      from normal discocytes to echinocytes, spherocytes, stomatocytes and acanthocytes
      were also observed in the blood of the rats treated with (131)I. Zinc
      supplementation to (131)I treated rats, significantly attenuated the adverse
      effects caused by (131)I on the levels of MDA, GSH, SOD and catalase. In
      conclusion, the study revealed significant oxidant/antioxidant changes in RBC
      following (131)I administration in rats, while zinc was shown to act as a
      radioprotector agent.

PMID- 16617390
TI  - Technetium-99m-dimercaptosuccinic acid renal scintigraphy in children with
      urinary tract infections.
AB  - The aim of this study was to determine the incidence of abnormal
      dimercaptosuccinic acid-Tc-99m ((99m)Tc-DMSA) renal scintigraphy findings in
      children with culture proved urinary tract infection (UTI) with or without
      vesicoureteral reflux (VUR). (99m)Tc-DMSA renal scintigraphy was performed in 343
      children with culture documented UTI (247 girls and 96 boys) aged from three
      months to 14 years (middle age of 4.82 years). The children studied were all
      those submitted for renal scintiscan to the Institute of Nuclear Medicine,
      Military Medical Academy, Belgrade during a five-year period (2000-2004).
      Micturating cystoureterography (MCU) performed in all patients before (99m)Tc
      DMSA scan, revealed VUR in 213 children, while in 130 children VUR was not
      detected by MCU. In 15 of the 213 children the grade of VUR was I, in 88 was II,
      in 57 was III, in 33 was IV and 20 children had grade V of VUR. Findings of
      (99m)Tc-DMSA renal scintigraphy were classified as: normal, equivocal and
      abnormal. Statistical analysis was performed using c(2)test. In all patients
      abnormal findings were detected in 38% (131/343), normal in 51% (174/343) and
      equivocal findings in 11% (38/343). In children with UTI and VUR the incidence of
      abnormal findings was 53% (112/213), of normal 37% (80/213) and of equivocal
      findings 10% (21/213). In children with UTI without VUR the incidence of abnormal
      findings was 15% (19/130), of normal findings 72% (94/130), and of equivocal
      findings 13% (17/130). The incidence of abnormal findings was significantly
      higher in children with UTI and VUR than in those with UTI without VUR (P<0.001).
      In children with VUR grades I, II, III, IV and V abnormal findings were 33%, 32%,
      60%, 79% and 95% respectively. The incidence of abnormal findings was higher in
      children with VUR grades IV and V, than in grade I and II (P<0.001). Our results
      suggest that (99m)Tc-DMSA renal scintigraphy in children can discriminate between
      grade I-II and IV-V of VUR and also that in children with UTI and VUR abnormal
      findings in the scintiscan were more than three times higher than in children
      with UTI alone.

PMID- 16617391
TI  - The brain scintiscan with iodine-123-ioflupane to diagnose early Parkinson's
      disease; seven months follow up. First results in Bulgaria.
AB  - The aim of this study was to evaluate the brain scintiscan images with (123)I
      ioflupane for the diagnosis of patients with early Parkinson's disease (PD).
      Sixteen patients were studied, nine males and seven females, aged between 38-81 y
      (mean age: 64 y). All patients underwent thyroid blocking by oral administration
      of 120 mg potassium iodide before and 24 h after the intravenous (iv) injection
      of 110-185 MBq/70 kg patient's weight, of (123)I-ioflupane. To check the correct
      biodistribution of the radiopharmaceutical, whole-body scans were performed at 15
      min and 2-3 h after the administration of the radiopharmaceutical. All patients
      underwent brain single photon emission tomography (SPET) scans on a SPET gamma
      camera 3-5 h after (123)I-ioflupane administration. To compensate for scatter and
      to avoid artifacts, the filtering and reconstructing procedures of the images
      were performed individually for each patient. Brain SPET results were evaluated
      semi-quantitatively using different indices. The morphology of the nigrostriatum
      (NS) area was also examined visually. The (123)I-ioflupane uptake by the affected
      nigrostriatum (ANS) was compared to a similar area at the occipital (Occ) brain
      section and to a similar area at the opposite NS. When the value of ANS/Occ was
      within the confidence limit of 1.507-1.636 and the value of ANS/NNS was within
      the limit of 0.755-0.889, PD was diagnosed (P<0.05). Thirteen of our patients
      were diagnosed as having PD and were given l-DOPA treatment. In the remaining
      patients the diagnosis of PD was rejected due to normal scintigraphic and
      morphologic findings of the NS area. The interest of this article lies in the
      following: The correct distribution of the radiopharmaceutical was confirmed by
      whole body scintiscan. Parameters for better quality of imaging were individually
      selected for each patient. The morphology of the NS areas, as estimated visually
      by us, was in accord with the scintigraphic (123)I-ioflupane uptake. The
      diagnosis of PD was clinically confirmed after treatment with l-DOPA in a seven
      month follow up period. Results from the small number of cases studied showed:
      93% sensitivity and maximum specificity for the diagnosis of PD.

PMID- 16617392
TI  - Increased serum carbohydrate antigen 19-9 in relapsed ductal breast carcinoma.
AB  - Increased serum carbohydrate antigen (CA) 19-9 is a quite uncommon manifestation
      of breast cancer both on early disease and on relapse. A 53-year-old woman with
      invasive ductal breast carcinoma underwent left-sided mastectomy. Two years later
      she palpated a subcutaneous mass at the mastectomy scar, arousing suspicion of
      local relapse. Surgery and histopathology revealed infiltration by breast
      adenocarcinoma and she was treated with chemotherapy. At that time serum tumor
      markers, carcinoembryonic antigen (CEA) and CA 15-3 were within normal range.
      Over the next six months she displayed an increase of serum CEA while serum CA 15
      3 remained within normal range. In an attempt to search for a second neoplasm
      possibly of gastrointestinal (GI) origin, abdominal computed tomography (CT),
      magnetic resonance imaging (MRI), magnetic resonance cholangio-pancreatography
      (MRCP), endoscopy of the upper GI tract and colonoscopy were performed, as well
      as measurement of serum CA 19-9. While no indication of a GI neoplasm was
      detected, she displayed an over 10-fold increase of serum CA 19-9. The patient
      had also an X-ray mammography and technetium-99m hexakis-2
      methoxyisobutylisonitrile ((99m)Tc-MIBI) scintimammography (SM). Whilst
      mammography was negative for contralateral disease recurrence, SM was suggestive
      of axillary lymph node involvement. Axillary lymph node dissection confirmed an
      extensive metastatic infiltration of these nodes by breast adenocarcinoma. Three
      months later serum CA 19-9 and CEA became normal. The interest of this case lies
      on the unexpected high serum CA 19-9 values found in a breast relapsed
      adenocarcinoma and in the important contribution of SM in diagnosing the axillary
      lymph node metastatic infiltration.

PMID- 16617393
TI  - Primary papillary carcinoma in a thyroglossal duct cyst.
AB  - Thyroglossal duct cysts (TDC) are the most common congenital anomalies of the
      thyroid gland and less than 1% of them become malignant. The malignancy most
      often found is papillary carcinoma. The diagnosis is usually made
      postoperatively. Controversy exists whether TDC are primary or secondary and also
      as for their treatment regime. In this case report, we present a 30-year-old
      woman with papillary carcinoma of the TDC, identified only by pathology after
      surgical ablation by Sistrunk's procedure. Invasion of the carcinoma to the
      adjacent tissues or lymph node metastases were not found. Thyroid function tests
      were normal as well as the thyroid scan. After a two-year follow up, the patient
      remained asymptomatic with no evidence of recurrence, as tested clinically and by
      ultrasonography. Since our patient had no marginal invasion of the carcinoma in
      the surrounding tissues or lymph node metastases, we recommended the Sistrunk's
      surgical procedure, suppressive treatment by thyroid hormones and long term
      follow-up.

PMID- 16617394
TI  - About mentioning quality of preparation and quality control of
      radiopharmaceuticals used in nuclear medicine procedures.

PMID- 16617396
TI  - Inspiration-sleep-rest and nuclear medicine.

PMID- 16617397
TI  - [The contribution of nuclear medicine in the diagnosis of depression].
AB  - Depression is an important and common disease, yet only recently, techniques of
      nuclear medicine like positron emission tomography and single photon emission
      tomography along with functional magnetic resonance imaging have greatly
      contributed to the diagnosis, follow up and research of depression. In the
      present article we describe and discuss briefly the sites of the brain related to
      depression as these sites have been studied by nuclear medicine techniques. We
      especially refer to the role of hippocampus, amygdala, the frontal cortex,
      striatus, pallidum, thalamus and cerebellum.

PMID- 16617398
TI  - [Metabolites of arachidonic acid in activating platelets and their estimation by
      radionuclide techniques].
AB  - This article reviews our current knowledge of the role of oxygen free radicals
      (OFR) in the process of arachidonic acid metabolism and platelet activation.
      During this activation several platelet enzymatic products are formed, which are
      measured by radioimmunoassays (RIA) and radioimmunometric assays (IRMA). Many
      studies have indicated that platelets are able to produce OFR, which are likely
      to play a significant role in the mechanisms of platelets activation and
      aggregation. These findings are important because they show that OFR may have a
      significant role in the mechanism of atherosclerosis and thrombosis. The role of
      several antioxidant factors in platelets' activation and aggregation is also
      presented in this review. It was found that antioxidant substances which act like
      OFR "scavengers" cause inhibition of arachidonic acid derivatives production and
      also inhibition of platelets activation. These studies suggest the possible
      therapeutic intervention with antioxidants acting as antiplatelet agents, to
      improve the pharmacological effects of various antiplatelet drugs. Finally we
      present our studies related to the arachidonic acid metabolites. The
      determination of arachidonic metabolic derivatives as thromboxane A(2),
      prostaglandin E(2), prostacyclin I(2) and isoprostane 8-iso-PG F(2alpha) by RIA
      and IRMA tests is important for the actual study of the above metabolic
      mechanisms because these tests are more accurate and less expensive, as compared
      to routine ELISA and other similar tests used for the same purpose.

PMID- 16617399
TI  - [The clinical and laboratory findings in Graves' multinodular type disease].
AB  - Graves' disease (GD) is an autoimmune thyroid disease characterized among other
      findings by diffuse goiter. It is possible in GD to find a multinodular goiter
      (mGD). Are they two different diseases that coexist, or do we have a multinodular
      type of GD. Questions arise as for the time that this mGD appears in the process
      of GD and also, as for the clinical and laboratory characteristics of mGD. To
      answer these questions, we have studied retrospectively and randomly from the
      archives of the Department of Nuclear Medicine of AHEPA University Hospital, from
      2000-2004, 20 female patients with multinodular type of GD (Group A) as first
      diagnosed by us and 50 female patients with diffuse type of GD (Group B) of about
      the same age. Patients with mGD had been examined before by us and their GD was
      documented. No other cause for exophthalmus except GD was found. Patients with
      any other additional disease were excluded from the study. All patients had 7-10
      signs of hyperthyroidism (thyroid index). Many of the patients, after the present
      study, were given (131)I therapeutically. These groups were divided in subgroups
      of pre- and menopausal women (A1, B1 and A2, B2 respectively). The mean age of
      our patients in Groups A and B were 46 and 50 years with a range of 25-65 and 38
      69 years respectively. Serum free triodothyronine (FT3), free thyroxine (FT4),
      thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (AbTPO),
      antithyroglobulin antibodies (AbTG) and anti receptors of thyroid stimulating
      hormone antibodies (AbTSHR) were tested in all subjects studied by
      radioimmunoassays (RIA) or radioimmunometric assays (IRMA). All patients were
      under antithyroid treatment interrupted for about 10 days before the thyroid
      scan. Thyroid scintiscan was performed 24 h after oral intake of 1.8 MBq of
      (131)I. Clinical findings were evaluated by a clinical index of hyperthyroidism
      as modified by us. The time that the mGD appeared since the beginning of GD and
      the time the GD started were also studied. Our findings were as follows: A mean
      time of 10.35+/-6.7 years had elapsed from the start of GD till mGD was first
      diagnosed by us. A mean time of 3.1+/-1.6 years had elapsed after the start of
      the GD till patients of Group B were examined in this study. No difference in the
      values of FT3, FT4 and TSH between the two Groups or the Subgroups was found as
      expected because the clinical status of the patients varied. AbTG, AbTPO and
      AbTSHR were found in a much higher incidence and in higher values in Group A
      versus Group B (P=0.007 and 0.001 respectively) and in Subgroups A1, A2 versus B1
      and B2 respectively. This increase was significant for AbTG and AbTPO in A2
      versus B2 Subgroups and for AbTPO in A1 versus B1 Subgroups (P=0.007, 0.001 and
      0.014 respectively). We were unable to find a similar work in the literature. In
      conclusion, we suggest that mGD as compared to GD: a)develops late in GD and thus
      patients had more relapses, b) has a higher incidence of abnormal values of
      AbTPO, AbTG and AbTSHR, c) has significantly higher values of AbTPO and less of
      AbTG than GD and d) thyroid hormones, clinical index of hyperthyroidism and the
      incidence of exophthalmos do not differ. Based on the above, we suggest that mGD
      is a late evolutionary type of GD. The study of patients of both sexes having GD
      of the same duration as mGD, the study of iodine metabolism and of thyroid gland
      pathology in these patients, is needed.

PMID- 16617400
TI  - [Procollagen-I, collagen telopeptide I, CEA, CA 15-3 as compared to bone
      scintigraphy in patients with breast cancer].
AB  - The most common metastases of breast cancer (BC) are bone metastases. Serum pro
      Iota collagen peptide (PICP) and I collagen telopeptide (ICTP) levels indicate
      the rate of bone collagen synthesis and bone resorption respectively and
      therefore indicate metastatic activity in the bone. We have studied the clinical
      importance of serum PICP and ICTP as well as CA 15-3 and CEA and compared them to
      bone scintigraphy findings indicating metastases from BC. Ninety seven women of
      mean age 58+/-8 years with BC were examined. The diagnosis of BC was
      histologically confirmed. Bone metastases were diagnosed in 68 of them by bone
      scans performed after the intravenous injection of 925 MBq of technetium-99m
      methylendiphosphonate, while 29 patients were free from bone metastases. We also
      examined 52 women of similar age, as controls. Serum PICP, ICTP, CA 15-3 and CEA
      were measured in both patients and controls. Serum levels of ICTP and CA 15-3
      were significantly higher in patients with BC and bone metastases compared to
      patients without metastases (P<0.05), while PICP and CEA were only marginally
      higher. A statistically significant correlation was observed between the
      existence of bone metastases and ICTP serum levels (P<0.05). The sensitivity of
      PICP, ICTP, CEA and CA 15-3 was 28.1%, 48.6%, 78%, 42% respectively and their
      specificity was 83.9%, 94%, 65% and 86% respectively. IN CONCLUSION: ICTP and CA
      15-3 are the most reliable markers of those studied for the diagnosis of bone
      metastases in BC. PICP alone or combined with ICTP were not sensitive enough. CA
      15-3 showed sensitivity 78% and specificity 86%. When combining CA 15-3, ICTP and
      CEA the sensitivity and specificity increased to 82% and 96% accordingly.

PMID- 16617401
TI  - [Radiation doses from patients undergoing yttrium-90 silicate knee
      radiosynovectomy].
AB  - The present study was undertaken because we could not find references related to
      the minimal radiation doses emitted from patients treated with (90)Y-silicate
      colloid ((90)Y-SC) for radiosynectomy (RS). Radiation doses from 16 patients
      treated with about 181+/-13 MBq (90)Y-SC for RS of knee synovitis were estimated
      by dose rate measurements performed within 10 min after the (90)Y-SC injection
      with a calibrated survey dose ratemeter at 0.5 m, 1 m and 2 m distances from the
      treated joint. The mean dose rate values from the patients after bg subtraction
      were 0.6+/-0.4 microSv/h at 0.5 m, 0.1+/-0.1 microSv/h at 1 m and 0.1 +/- 0.0
      microSv/h at 2 m distance. Dose rates at a distance of 0.5 m were significantly
      correlated (P<0.02) with the patient's weight but not with the height or the
      injected activity. The assumed estimated maximum whole body doses from a treated
      patient were 55 microSv for persons living with the patient, 2.9-3.4 microSv for
      the nursing staff, 0.2-1.8 microSv for the therapist physician and 0.3-0.6
      microSv for the technologist, involved in the whole procedure. The above values
      were lower than those published with the same methodology for alternative RS
      radiopharmaceuticals for knee synovitis like dysprosium-165 ferric hydroxide
      macroaggregate ((165)Dy-FHMA) or holmium-166 ((166)Ho-FHMA), as estimated with
      their typical injected activities. In conclusion our results demonstrate that in
      (90)Y-SC knee synovectomy, the whole body radiation doses to medical and non
      medical personnel were as expected well below the maximum annual dose limits for
      the public and professionals exposed to radiation.

PMID- 16617402
TI  - [Scintigraphic imaging of knee synovitis in osteoarthritis after intra-articular
      injection of technetium-99m pertechnetate in the unilateral knee].
AB  - A case of left knee synovitis scintigraphic imaging is presented in a 66-year-old
      patient with bilateral knee osteoarthritis and a right knee Baker's cyst, who had
      undergone a 74 MBq (99m)Tc-pertechnetate intra-articular injection in the right
      knee. The findings in this case were compared with the intravenously injected
      methylene disphosphonate technetium-99m ((99m)Tc-MDP) scintigraphic findings and
      could be interpreted as the result of (99m)Tc-pertechenate through blood
      communication from the right to the left knee. This case implies that (99m)Tc
      pertechnetate may be useful in imaging the synovitis in multiple arthroses even
      up to 60 min after its administration, instead of the 5 min imaging after the
      injection of (99m)Tc-MDP.

PMID- 16617403
TI  - Syndecan-1 as a mediator of bacteria-enterocyte interactions.

PMID- 16617404
TI  - Sleep patterns of school-age children with Asperger syndrome or high-functioning
      autism.
AB  - Sleep patterns of 32 school-age children with Asperger syndrome (AS) and high
      functioning autism (HFA) were compared to those of 32 typically developing age-
      and gender-matched children, using parent survey and one week of diary and
      actigraphic monitoring. Parents of children with AS/HFA more commonly reported
      that their children had difficulty falling asleep. One week of sleep recording
      with diary and actigraphy confirmed that children in the AS/HFA group spent a
      longer time awake in bed before falling asleep than children in the control
      group, possibly because the children in the AS/HFA group had earlier bedtimes.
      Other essential aspects of sleep patterns coincided between the groups. The sleep
      patterns of children with AS and HFA did not differ.

PMID- 16617405
TI  - Refinement of the Children's Social Behavior Questionnaire (CSBQ): an instrument
      that describes the diverse problems seen in milder forms of PDD.
AB  - The objective of this study was to refine the Children's Social Behavior
      Questionnaire (CSBQ), to reduce its length, and to verify its psychometric
      properties. The CSBQ is a questionnaire for parents or caregivers of children
      with PDD. The items describe a broad range of features that are typical of PDD,
      particularly in its milder forms. Based on conceptual judgment and factor
      analyses, the number of items was reduced from 96 to 49. Six subscales were
      constructed to allow a differentiated description of PDD problems. Estimates for
      internal, test-retest, and inter-rater reliability, and for convergent and
      divergent validity were good. Different clinical and control groups showed the
      hypothesized patterns in nature and degree of their problems.

PMID- 16617406
TI  - Treatment related myelitis in Hodgkin's lymphoma following stem cell transplant,
      chemotherapy and radiation: a case report and review of the literature.
AB  - Radiation myelitis, while rare, is one of the most devastating complications of
      radiation treatment. We report here a case of a 25-year-old Middle Eastern man
      with progressive myelopathy 21 months following low dose irradiation of the cord
      in the context of high dose chemotherapy and stem cell rescue and a review of the
      literature.

PMID- 16617407
TI  - Ion release from gold/platinum dental alloy: could release of other elements be
      accountable in the contact allergy attributed to the gold?
AB  - OBJECTIVES: The release of metal ions (Al, Ag, Au, Ca, Cd, Co, Cr, Cu, Mg, Mo,
      Ni, Pd, Pt, Ti, and Zn) from the commercial gold/platinum (Au/Pt) dental alloy of
      declared composition was studied. METHODS: Au/Pt was soaked in pH 6.0 phosphate
      buffer, 3.5 pH phosphate buffer and pH 3.5 mixture of lactic, formic and acetic
      acid, and incubated at 37 degrees C for 1, 2, 3, 4, 5, 6, 7, 14, 21, and 30 days.
      Six samples (n = 6) of every solution were prepared for any time period.
      Inductively coupled plasma atomic emission spectroscopy was used for analysis of
      the released elements. RESULTS: Results demonstrated release of only Cr, Cu, Fe,
      and Zn from the tested Au/Pt dental alloy (ANOVA, p < 0.001 for buffer, time, and
      interaction, respectively); however, only Cu and Zn were declared. CONCLUSIONS:
      The undeclared chromium from Au/Pt dental alloy, or some other element might be
      responsible for the contact allergy thus far attributed to the gold.

PMID- 16617408
TI  - Optimisation of the composition of an acrylic bone cement: application to
      relative amounts of the initiator and the activator/co-initiator in Surgical
      Simplex P.
AB  - In cemented arthroplasties, the two-part self-curing acrylic bone cement is
      currently the only material used for anchoring the total joint replacement to the
      contiguous bone. In virtually all commercially available formulations of this
      cement, the agents used for the initiation and activation/co-initiation of the
      radical polymerisation reaction are benzoyl peroxide (BPO) and N, N dimethyl-para
      toluidine (DMPT), respectively. There are no reports in the open literature on
      the rationale for the amounts of these and other constituents in the formulations
      of the cement. Given the concerns that have been raised in the literature
      regarding the effect of residual DMPT on the body, it is important to keep the
      starting amounts of BPO and DMPT as high and as low, respectively, as possible.
      In the present work, the focus is on the relative amounts of these two agents in
      the case of one widely used commercial formulation, Surgical Simplex(R) P. Thirty
      variants of this cement were formulated, covering three concentrations of the co
      polymer/BPO (75%, 80%, and 85% of the mass of the powder) and DMPT amounts
      (ranging from 0.8 %v/v to 2.4% v/v.) The setting time (t(set)), the peak
      temperature reached during the cement polymerisation process (T(max)), and the
      ultimate compressive strength (UCS) of each of the formulations were determined
      in accordance with procedures specified in ISO 5833. A critical examination of
      all the results indicated that the optimum ratio of the concentration of the
      initiator (BPO embedded in the PMMA-sytrene co-polymer) to that of the
      activator/co-initiator (DMPT) in Surgical Simplex(R) P is 57.14 (80%w/w co
      polymer + BPO per 1.4%v/v DMPT). The mean values of t(set), T(max), and UCS of
      this optimum formulation were determined to be 12.30 min, 68 degrees C, and 101
      MPa, respectively, all of which are within the limits specified in ISO 5833. The
      commercially available formulation of this cement contains 2.5%v/v DMPT, while
      the optimum formulation, as found in the present work, has 44% less DMPT, which
      may translate to a smaller amount of residual DMPT that is available for elution
      into the periprosthetic tissue in a cemented arthroplasty, over the in vivo life
      of the joint replacement.

PMID- 16617409
TI  - Ultrasonically set glass polyalkenoate cements for orthodontic applications.
AB  - There is an accepted clinical requirement for a luting cement that can be command
      set upon satisfactory placement of an orthodontic appliance onto dentition. This
      work evaluates the suitability of ultrasound, imparted from a dental scaler, as a
      potential mechanism for achieving this. The net setting times and subsequent
      compressive strengths of a range of commercial and experimental glass
      polyalkenoate cements (GPCs) were evaluated, using modified ISO 9917 methods,
      when set both chemically and by ultrasound. The ultrasound was applied to the GPC
      through an orthodontic brace. It was possible to command set GPCs by the
      application of five to ten seconds of ultrasound; the exact time required being
      dependent upon the composition of the GPC in question. The compressive strengths
      of these cements can be improved by around 90% with the command set when the
      optimum PAA molecular weight and tartaric acid content is employed.

PMID- 16617410
TI  - Swelling properties and bioactivity of silica gel/pHEMA nanocomposites.
AB  - A novel hydrogel based on 2-hydroxyethyl- methacrilate and SiO(2) nanoparticles
      was prepared. The filler was added at a concentration of 30% w/w of silica
      nanoparticles to the mass of polymer. The composite material was characterised as
      far as concerns swelling behaviour in comparison to pHEMA. Swelling ratio of
      modified pHEMA was higher. Bioactivity of both SiO(2) nanoparticles and the
      modified hydrogel was evaluated by soaking samples into a simulated body fluid
      (SBF). FT-IR spectroscopy, scanning electron microscopy (SEM) and energy
      dispersive system (EDS) results suggest silica nanoparticles keep bioactive in
      the polymer. SiO(2) filler in a p(HEMA) matrix makes the composite bioactive.
      Therefore, these composites can be used to make bioactive scaffold for bone
      engineering.

PMID- 16617411
TI  - Influence of the porosity of hydroxyapatite ceramics on in vitro and in vivo bone
      formation by cultured rat bone marrow stromal cells.
AB  - The in vitro and in vivo osteoblastic differentiation of rat bone marrow stromal
      cells (MSCs) was assessed on hydroxyapatite disks with 3 different porosities:
      30%, 50%, and 70% (HA30, HA50, and HA70, respectively). MSCs obtained by 10-day
      culture of fresh bone marrow cells were subcultured for 2 weeks on 3 kinds of
      porous HA disks in the presence and absence of dexamethasone (Dex). After 2 weeks
      of subculture, alkaline phosphatase (ALP) activity and osteocalcin production of
      MSCs/HA composites with Dex were higher than those without, and increased with
      increasing porosity. The resultant bone tissue grafts "cultured-bone/HA
      constructs" were implanted subcutaneously into the backs of syngeneic rats, and
      harvested 1, 2, and 4 weeks after implantation. At 1 week, only cultured
      bone/HA70 constructs exhibited expanded bone formation. At 2 and 4 weeks, active
      osteoblasts and progressive bone formation were observed morphologically in both
      cultured-bone/HA50 and HA70 constructs. At 4 weeks, bone tissue was observed even
      in cultured-bone/HA30 constructs. ALP activity and osteocalcin production also
      increased with increasing porosity and time after implantation. In this in vivo
      model, different scaffold porosity with similar crystal morphology of the apatite
      phase demonstrated marked differences in ability to support osteogenesis by
      implanted rat MSCs.

PMID- 16617412
TI  - The effects of types of degradable polymers on porcine chondrocyte adhesion,
      proliferation and gene expression.
AB  - Understanding how a specific biomaterial may influence chondrocyte adhesion,
      proliferation and gene expression is important in cartilage tissue engineering.
      In this study several biodegradable polymers that are commonly used in tissue
      engineering were evaluated with respect to their influence on chondrocyte
      attachment, proliferation and gene expression. Primary cultures of porcine
      chondrocytes were performed in films made of poly-L-lactic acid (PLLA), poly-D,L
      lactic acid (PDLLA), poly-(lactide-co-glycolide) (PLGA), or polycaprolactone
      (PCL). Chondrocytes adhered to PDLLA or PLGA after 1-day incubation better than
      to PLLA or PCL. After 7 or 14 day culture, the cell numbers on PDLLA or PLGA was
      still higher than PLLA or PCL. The results suggested that cell attachment and
      growth might depend on degradation rate of biodegradable polymers. Along with the
      fact that PDLLA or PLGA supported expression of chondrocyte specific genes more
      than PLLA or PCL, the former two materials seemed to be more suitable for
      cartilage tissue engineering than the latter ones. Besides, we found that
      chondrocyte phenotype prior to seeding was important in the expression of ECM
      proteins.

PMID- 16617413
TI  - Design of gelatin nanoparticles as swelling controlled delivery system for
      chloroquine phosphate.
AB  - Gelatin nanoparticles were prepared by a single W/O emulsion technique and
      characterized by infrared (IR) spectra, scanning electron microscopy (SEM) and
      particle size analysis. The prepared nanoparticles were loaded with chloroquine
      phosphate (CP), a well known antimalarial drug, and the release dynamics of
      entrapped drug was investigated as a function of various experimental factors
      such as percent loading of the drug, chemical architecture of the nanocarriers,
      and pH, temperature, ionic strength and nature of the release medium. The
      nanoparticles were also studied for their water sorption capacity by optical
      microscopic method taking advantage of the aggregation of nanoparticles. The drug
      release processes was analyzed kinetically using Ficks power law and a
      correlation was established between the quantity of released drug and swelling of
      the nanoparticles.

PMID- 16617414
TI  - Hepatocyte spheroid formation on a titanium dioxide gel surface and hepatocyte
      long-term culture.
AB  - The cell morphology and expression of differentiated functions of primary rat
      hepatocytes on a titanium dioxide (TiO(2)) gel surface were investigated.
      Polystyrene culture dishes were coated with TiO(2) gel by spin-coating an ethanol
      solution of titanium n-butoxide, hydrolyzing in a humidity chamber and drying
      with nitrogen gas. The TiO(2) gel layer formed on the polystyrene dishes was
      transparent and robust, and its surface was quite flat. Rat hepatocytes
      inoculated on the TiO(2) gel-coated polystyrene dishes gradually accumulated with
      increasing culture time, and then spontaneously formed many hepatocyte spheroids
      at 90 +/- 21 microm diameter from about 3 days of culture. The diameter of the
      spheroids increased during the culture, and was 151 +/- 43 microm at 14 days of
      culture. Ammonia removal and albumin secretion by hepatocytes on the TiO(2) gel
      coated polystyrene dishes were maintained at a high level for at least 14 days of
      culture compared with on a type I collagen-coated dish and a non-coated
      polystyrene dish. These results indicate that TiO(2) gel is an adequate material
      for hepatocyte spheroid formation and long-term culture of spheroids.

PMID- 16617415
TI  - Effects of temperature and strain level on stress relaxation behaviors of
      polypropylene sutures.
AB  - An investigation has been conducted on stress relaxation behaviors of
      polypropylene sutures under different temperatures and strain levels in a
      temperature-controlled water bath. The study showed that the temperature and
      strain level significantly affected the stress relaxation behaviors of the
      sutures. High temperature resulted in fast stress relaxation. The stress
      relaxation data could be well described by two empirical formulas. For most of
      the test conditions, the stress relaxation tests caused limited permanent
      deformation in sutures. Effects of temperature on the permanent deformation may
      be illustrated by a power law. The tensile properties of the sutures were not
      affected adversely by the stress relaxation tests, indicating good properties of
      polypropylene sutures.

PMID- 16617416
TI  - Starch-based microspheres produced by emulsion crosslinking with a potential
      media dependent responsive behavior to be used as drug delivery carriers.
AB  - This paper describes the development and characterization of starch microspheres
      for being used as drug delivery carriers in tissue engineering applications. The
      developed starch microspheres can be further loaded with specific growth factors
      and immobilized in scaffolds, or administrated separately with scaffolds.
      Furthermore and due to the processing conditions used, it is expected that these
      microspheres can be also used to encapsulate living cells. The aim of this study
      was to evaluate the efficacy of this methodology for further studies with
      biologically active agents or living cells. The starch microspheres were prepared
      using an emulsion crosslinking technique at room temperature to allow for the
      loading of biologically active agents. A preliminary study was performed to
      evaluate the incorporation of a model drug (nonsteroidal anti-inflammatory drug
      NSAID) and investigate its release profile as function of changes in the medium
      parameters, such as ionic strength and pH. The developed starch-based drug
      delivery system has shown to be dependent on the ionic strength of the release
      medium. From preliminary results, the release seems to be pH-dependent due to the
      drug solubility. It was found that the developed microspheres and the respective
      processing route are appropriate for further studies. In fact, and based in the
      processing conditions and characterization, the developed system present a
      potential for the loading of different growth factors or even living cells on
      future studies with these systems for improving bone regeneration in tissue
      engineering, especially because the crosslinking reaction of the microspheres
      takes place at room temperature.

PMID- 16617417
TI  - Hydrolyses of calcium phosphates-allografts composite in physiological solutions.
AB  - Hydrolysis of calcium phosphates cement- allografts composite in calf serum and
      that in saline were examined in comparison with those of the calcium phosphates
      cement in both the solutions. The calcium phosphates cement consists of alpha
      tricalcium phosphate (alpha-TCP), tetracalcium phosphate (TetCP), dicalcium
      phosphate dihydrate (DCPD), and hydroxyapatite (HAP), which is clinically used as
      Biopex. In the hydrolyses of Biopex-allografts composite in both the solutions,
      the calcium phosphates cement was transformed into HAP. On the other hand, in the
      hydrolyses of Biopex, HAP was formed after 1 day and octacalcium phosphate (OCP)
      was gradually formed after 7 days. In the presence of allografts, plate-like
      crystals were deposited and in the absence of allografts, needle-like crystals
      were deposited in both the solutions. By the addition of allografts, the
      hydrolysis process of the calcium phosphates cement was significantly changed.

PMID- 16617418
TI  - Organic-inorganic interaction and the growth mechanism of hydroxyapatite crystals
      in gelatin matrices between 37 and 80 degrees C.
AB  - The crystal development of hydroxyapatite[HAp] phase in gelatin[GEL] matrices was
      investigated in the temperature range 37 to 80 degrees C by using X-ray
      diffraction, scanning electron microscopy(SEM), thermoanalytical
      measurement(DT/TGA), Fourier-Transformed Infra-Red(FT-IR) spectroscopy, and
      transmission electron microscopy(TEM) with electron diffraction(ED). It was found
      that during the coprecipitation of apatite phase in GEL matrices and the next
      aging process the crystallites were formed and developed through the two reaction
      mechanisms of organic-inorganic interaction between apatite phase and GEL
      molecules, and thermodynamic reaction for the crystal growing. The analytical
      evidences showed that there was a definite competition between these two
      mechanisms with the reaction temperature. Below 50 degrees C the crystal
      development of HAp was greatly suppressed by the existence of the GEL molecules,
      indicating the heterogeneous nucleation by the supposed number of carboxyl groups
      in GEL. Above 50 degrees C the effective organic components as a template for the
      heterogeneous nucleation of apatite crystallites were greatly degraded and so
      more amount of inorganic ions could be favorably accredited on the preexisting
      crystallites in virtue of the limited nucleation chance, finally resulting in the
      crystal growth. At higher temperature pretty big HAp crystals were developed with
      the depletion of the organics to be bound with crystallites in the slurry
      solution. Presumably it is believed that the poisoning of the functional groups
      in GEL molecules was vigorously occurred in the phosphoric acid environment above
      approximately 50 degrees C.

PMID- 16617419
TI  - Laparoscopic and retroperitoneoscopic treatment of pheochromocytomas and
      retroperitoneal paragangliomas: results of 161 tumors in 126 patients.
AB  - BACKGROUND: Laparoscopic and retroperitoneoscopic excisions of pheochromocytomas
      and retroperitoneal paragangliomas are challenging surgical procedures because of
      extensive intraoperative catecholamine release, extreme vascularization, and
      demanding localization. MATERIALS: In a prospective clinical study 161
      chromaffine neoplasias (134 pheochromocytomas, 27 paragangliomas) were removed
      endoscopically in 126 patients (67 males, 59 females, age 41.7 +/- 16.4 years;
      130 operations). Six patients showed multiple (2-5) tumors. Tumor size ranged
      from 0.5 to 12 cm (mean 3.5 +/- 1.9 cm). Forty-two patients suffered from
      hereditary diseases. Twenty-four patients had bilateral adrenal diseases; in 14
      patients pheochromocytomas were removed on both sides synchroneously. Ten
      neoplasias were local or loco-regional recurrences (7 pheochromocytomas, 3
      paragangliomas). The laparoscopic route was chosen in 16 operations; the
      retroperitoneoscopic technique was performed in 128 others. Partial
      adrenalectomies were performed in 57 operations (in all but one of the patients
      with bilateral disease). High-dosage alpha-blockade with phenoxybenzamine was
      routinely used. RESULTS AND DISCUSSION: Conversion to open surgery occurred once.
      Perioperative complications were minor (17%); mortality was zero. Operating time
      for unilateral retroperitoneoscopically removed primary pheochromocytomas (n =
      113) was 82 +/- 49 minutes (range: 20-300 minutes) and depended on tumor size (<
      3 cm vs. > or = 3 cm; P < 0.05) and gender (P < 0.001), but not on extent of
      resection (partial vs. total, P = 0.266). Operating time for paragangliomas
      ranged from 55 to 600 minutes. Median blood loss was 20 ml. Median duration of
      postoperative hospitalization was 4 days. In 22 of 24 patients with bilateral
      disease, complete preservation of cortical function was achieved. Locoregional
      and/or distant metastatic recurrence were found in 5 patients. CONCLUSIONS:
      Endoscopic removal of solitary, bilateral, multiple, and recurrent
      pheochromocytomas and retroperitoneal paragangliomas is feasible and safe, but
      surgeons need extensive experience in minimally invasive techniques, as well as
      in endocrine surgery.

PMID- 16617420
TI  - Abdominal visceral lesions in von Hippel-Lindau disease: incidence and clinical
      behavior of pancreatic and adrenal lesions at a single center.
AB  - INTRODUCTION: Von Hippel-Lindau disease (VHL) is a dominantly inherited multi
      system syndrome. Although pheochromocytoma is the hallmark endocrine neoplasm,
      pancreatic lesions occur frequently, and their management can be complex. This
      report describes 26 patients from a single institution with pancreatic or adrenal
      lesions (or both) in the background of VHL. METHODS: We reviewed records for all
      patients treated for adrenal (type 2 VHL) or pancreatic manifestations of VHL at
      our institution from 1990 to 2004. RESULTS: Forty patients with VHL were
      identified from 24 pedigrees; 26 (65%) had adrenal or pancreatic involvement (or
      both). Seven patients had isolated pheochromocytomas, 16 had isolated pancreatic
      lesions, and 3 had both. Of the 10 patients with pheochromocytomas, 4 had
      bilateral adrenal involvement. All but three pheochromocytomas were diagnosed in
      patients aged 40 years or younger. Of the 19 patients with pancreatic lesions, 8
      had cystic lesions, 8 had neuroendocrine tumors, and 3 had both. Of 11 patients
      with neuroendocrine tumors, 4 had metastases (3 hepatic, 1 nodal). No patient
      with cystic pancreatic lesions developed carcinoma. CONCLUSIONS: VHL should be
      familiar to the endocrine surgeon because of the high incidence (65% in our
      series) of visceral endocrine lesions (pancreas 40%, adrenal gland 18%, both 7%).
      As seen in other hereditary endocrinopathy syndromes, pheochromocytomas are
      frequently bilateral; therefore,close follow-up of the contralateral gland in
      young patients with a unilateral lesion is critical. Cystic lesions of the
      pancreas may be closely monitored, whereas neuroendocrine tumors should be
      removed because of the risk of metastasis. Pancreatic pathology is not uncommon
      in VHL patients with pheochromocytoma and should be sought during the
      preoperative assessment.

PMID- 16617421
TI  - Plant bioassays for an in situ monitoring of air near an industrial area and a
      municipal solid waste: Zilina (Slovakia).
AB  - The process of a bioindication of genotoxic effects of complex mixtures on the
      environment using higher plants is very appropriate and effective. We present the
      results of an in situ indication of the genotoxic effects of polluted environment
      near Zilina city. For a more complex monitoring we used: the Tradescantia
      micronucleus (Trad-MCN) assay, the Tradescantia microspore test and an evaluation
      of the abortivity of the pollen grains of native plant species. We found
      significant differences in the frequency of the micronuclei when using the Trad
      MCN test in local of Duben. The Tradescantia pollen abortivity test showed
      significant differences in the frequency of the abortive pollen grains between
      the exposed groups and the control group. By using native plant species in the
      pollen abortivity test we found significant differences in both of the two
      locations for the four following species during two consecutive years: Artemisia
      vulgaris, Melilotus albus, Trifolium pratense, Typha latifolia.

PMID- 16617422
TI  - Pathways and kinetics on photocatalytic destruction of aqueous phenol.
AB  - In this study, the TiO2 photocatalytic decomposition process of aqueous phenol
      was investigated. The intermediate products generated in the elementary reaction
      steps in the mineralization process were experimentally identified as
      hydroquinone, catechol and hydroxyhydroquinone. The concentration variations of
      these intermediate products with time passage were traced by high performance
      liquid chromatograph. The pathways of the decomposition process were given. Based
      on Langmuir isothermal theory and Langmuir-Hinshelwood mechanism, the multi
      compounds competition kinetic model was established. In this model, the observed
      time-dependent concentrations of phenol and the intermediate products were
      simulated.

PMID- 16617423
TI  - A screening test for the determination of ethylene sensitivity.
AB  - Ethephon, which releases ethylene within plant tissues after application, was
      chosen to perform assessments of the relative sensitivity of crops to ethylene
      and to determine which stages of plant development were most sensitive. The
      species chosen were: barley, wheat, oats, canola and field pea, all of which are
      important crops in the province of Alberta, Canada. Plants were treated with
      ethephon at one of 7 different stages. Plants were assessed for their vegetative
      and reproductive growth, including height, biomass, yield and seed quality.
      Visual symptoms were photographed and documented to compare them with symptoms
      caused by ethylene applied as a gas. It was concluded that in barley, wheat and
      canola the late vegetative and early reproductive stages were most sensitive, at
      least when sensitivity was defined as reductions in yield and quality. As for
      field pea, ethephon had no effect on yield but did cause increased numbers of
      pods, which in certain conditions could lead to increased yields. Significant
      effects on vegetative growth were only observed in the early vegetative stages of
      development but with no effects on yield. The screening protocol successfully
      identified sensitive cultivars and growth stages for further investigation of the
      effects of ethylene exposure.

PMID- 16617424
TI  - Characterisation of PM(10), PM(2.5) and benzene soluble organic fraction of
      particulate matter in an urban area of Kolkata, India.
AB  - In this study, the relationship between inhalable particulate (PM(10)), fine
      particulate (PM(2.5)), coarse particles (PM(2.5 - 10)) and meteorological
      parameters such as temperature, relative humidity, solar radiation, wind speed
      were statistically analyzed and modelled for urban area of Kolkata during winter
      months of 2003-2004. Ambient air quality was monitored with a sampling frequency
      of twenty-four hours at three monitoring sites located near traffic intersections
      and in an industrial area. The monitoring sites were located 3-5 m above ground
      near highly trafficked and congested areas. The 24 h average PM(10) and PM(2.5)
      samples were collected using Thermo-Andersen high volume samplers and exposed
      filter papers were extracted and analysed for benzene soluble organic fraction.
      The ratios between PM(2.5) and PM(10) were found to be in the range of 0.6 to
      0.92 and the highest ratio was found in the most polluted urban site. Statistical
      analysis has shown a strong positive correlation between PM(10) and PM(2.5) and
      inverse correlation was observed between particulate matter (PM(10) and PM(2.5))
      and wind speed. Statistical analysis of air quality data shows that PM(10) and
      PM(2.5) are showing poor correlation with temperature, relative humidity and
      solar radiation. Regression equations for PM(10) and PM(2.5) and meteorological
      parameters were developed. The organic fraction of particulate matter soluble in
      benzene is an indication of poly aromatic hydrocarbon (PAH) concentration present
      in particulate matter. The relationship between the benzene soluble organic
      fraction (BSOF) of inhalable particulate (PM(10)) and fine particulate (PM(2.5))
      were analysed for urban area of Kolkata. Significant positive correlation was
      observed between benzene soluble organic fraction of PM(10) (BSM10) and benzene
      soluble organic fraction of PM(2.5) (BSM2.5). Regression equations for BSM10 and
      BSM2.5 were developed.

PMID- 16617425
TI  - Computational mutagenesis studies of protein structure-function correlations.
AB  - Topological scores, measures of sequence-structure compatibility, are calculated
      for all 1,881 single point mutants of the human immunodeficiency virus (HIV)-1
      protease using a four-body statistical potential function based on Delaunay
      tessellation of protein structure. Comparison of the mutant topological score
      data with experimental data from alanine scan studies specifically on the dimer
      interface residues supports previous findings that 1) L97 and F99 contribute
      greatly to the Gibbs energy of HIV-1 protease dimerization, 2) Q2 and T4
      contribute the least toward the Gibbs energy, and 3) C-terminal residues are more
      sensitive to mutations than those at the N-terminus. For a more comprehensive
      treatment of the relationship between protease structure and function, mutant
      topological scores are compared with the activity levels for a set of 536
      experimentally synthesized protease mutants, and a significant correlation is
      observed. Finally, this structure-function correlation is similarly identified by
      examining model systems consisting of 2,015 single point mutants of bacteriophage
      T4 lysozyme as well as 366 single point mutants of HIV-1 reverse transcriptase
      and is hypothesized to be a property generally applicable to all proteins.

PMID- 16617426
TI  - Predicting calcium-binding sites in proteins - a graph theory and geometry
      approach.
AB  - Identifying calcium-binding sites in proteins is one of the first steps towards
      predicting and understanding the role of calcium in biological systems for
      protein structure and function studies. Due to the complexity and irregularity of
      calcium-binding sites, a fast and accurate method for predicting and identifying
      calcium-binding protein is needed. Here we report our development of a new fast
      algorithm (GG) to detect calcium-binding sites. The GG algorithm uses a graph
      theory algorithm to find oxygen clusters of the protein and a geometric algorithm
      to identify the center of these clusters. A cluster of four or more oxygen atoms
      has a high potential for calcium binding. High performance with about 90% site
      sensitivity and 80% site selectivity has been obtained for three datasets
      containing a total of 123 proteins. The results suggest that a sphere of a
      certain size with four or more oxygen atoms on the surface and without other
      atoms inside is necessary and sufficient for quickly identifying the majority of
      the calcium-binding sites with high accuracy. Our finding opens a new avenue to
      visualize and analyze calcium-binding sites in proteins facilitating the
      prediction of functions from structural genomic information.

PMID- 16617427
TI  - Analyzing large-scale structural change in proteins: comparison of principal
      component projection and Sammon mapping.
AB  - Effective analysis of large-scale conformational transitions in macromolecules
      requires transforming them into a lower dimensional representation that captures
      the dominant motions. Herein, we apply and compare two different dimensionality
      reduction techniques, namely, principal component analysis (PCA), a linear
      method, and Sammon mapping, which is nonlinear. The two methods are used to
      analyze four different protein transition pathways of varying complexity,
      obtained by using either the conjugate peak refinement method or constrained
      molecular dynamics. For the return-stroke in myosin, both Sammon mapping and PCA
      show that the conformational change is dominated by a simple rotation of a rigid
      body. Also, in the case of the T-->R transition in hemoglobin, both methods are
      able to identify the two main quaternary transition events. In contrast, in the
      cases of the unfolding transition of staphylococcal nuclease or the signaling
      switch of Ras p21, which are both more complex conformational transitions, only
      Sammon mapping is able to identify the distinct phases of motion.

PMID- 16617428
TI  - Hindlimb adaptations in Ourayia and Chipetaia, relatively large-bodied omomyine
      primates from the Middle Eocene of Utah.
AB  - North American omomyids represent a tremendous Eocene radiation of primates
      exhibiting a wide range of body sizes and dietary patterns. Despite this adaptive
      diversity, relatively little is known of the postcranial specializations of the
      group. Here we describe hindlimb and foot bones of Ourayia uintensis and
      Chipetaia lamporea that were recovered from the Uinta B member (early Uintan Land
      Mammal Age), Uinta Formation, Utah. These specimens provide insights into the
      evolution of postcranial adaptations across different body sizes and dietary
      guilds within the Eocene primate radiation. Body mass estimates based on talar
      measurements indicate that Ourayia uintensis and Chipetaia lamporea weighed about
      1,500-2,000 g and 500-700 g, respectively. Skeletal elements recovered for
      Ourayia include the talus, navicular, entocuneiform, first metatarsal, and
      proximal tibia; bones of Chipetaia include the talus, navicular, entocuneiform,
      and proximal femur. Both genera had opposable grasping big toes, as indicated by
      the saddle-shaped joint between the entocuneiform and first metatarsal. Both taxa
      were arboreal leapers, as indicated by a consistent assemblage of characters in
      all represented bones, most notably the somewhat elongated naviculars, the high
      and distinct trochlear crests of the talus, the posteriorly oriented tibial
      plateau (Ourayia), and the cylindrical head of the femur (Chipetaia). The closest
      resemblances to Ourayia and Chipetaia are found among the Bridger omomyines,
      Omomys and Hemiacodon. The results of our comparisons suggest that the later,
      larger, more herbivorous omomyines from Utah retained a skeletal structure
      characteristic of earlier, smaller North American omomyids.

PMID- 16617429
TI  - Orangutan positional behavior and the nature of arboreal locomotion in
      Hominoidea.
AB  - The Asian apes, more than any other, are restricted to an arboreal habitat. They
      are consequently an important model in the interpretation of the morphological
      commonalities of the apes, which are locomotor features associated with arboreal
      living. This paper presents a detailed analysis of orangutan positional behavior
      for all age-sex categories and during a complete range of behavioral contexts,
      following standardized positional mode descriptions proposed by Hunt et al.
      ([1996] Primates 37:363-387). This paper shows that orangutan positional behavior
      is highly complex, representing a diverse spectrum of positional modes. Overall,
      all orthograde and pronograde suspensory postures are exhibited less frequently
      in the present study than previously reported. Orthograde suspensory locomotion
      is also exhibited less often, whereas pronograde and orthograde compressive
      locomotor modes are observed more frequently. Given the complexity of orangutan
      positional behavior demonstrated by this study, it is likely that differences in
      positional behavior between studies reflect differences in the interplay between
      the complex array of variables, which were shown to influence orangutan
      positional behavior (Thorpe and Crompton 2005 Am. J. Phys. Anthropol. 127:58-78).
      With the exception of pronograde suspensory posture and locomotion, orangutan
      positional behavior is similar to that of the African apes, and in particular,
      lowland gorillas. This study suggests that it is orthogrady in general, rather
      than forelimb suspend specifically, that characterizes the positional behavior of
      hominoids.

PMID- 16617430
TI  - Late Chachapoya population structure prior to Inka conquest.
AB  - Archaeological and ethnohistorical documents suggest that the Chachapoya region
      was inhabited by a number of distinct sociopolitical groups that only united in
      the face of their common enemy, the Inka. The purpose of this research is to
      quantify the amount of internal genetic differentiation and levels of
      extraregional gene flow during the Late Chachapoya period, in order to obtain a
      better understanding of the genetic relationship between these presumed ethnic
      groups. Craniometric data were collected from three Late Chachapoya samples
      (Laguna Huayabamba, Kuelap, and Laguna de los Condores), in order to understand
      the genetic relationships between the groups and facilitate our understanding of
      Late Chachapoya population structure. Genetic differentiation among these series
      ranged from 0.047 (heritability = 1.0) to 0.090 (heritability = 0.55). The
      Relethford-Blangero residuals indicate that the Laguna Huayabamba and Laguna de
      los Condores populations were receiving greater than average external gene flow,
      while Kuelap was receiving less than average external gene flow. The
      correspondence between biological and archaeological data in the investigation of
      prehistoric ethnic identity is discussed.

PMID- 16617431
TI  - Brief communication: linear enamel hypoplasia and the shift from irregular to
      regular provisioning in Cayo Santiago rhesus monkeys (Macaca mulatta).
AB  - This study investigates changes in the prevalence of linear enamel hypoplasia
      (LEH) before and after the shift from irregular to regular provisioning in the
      Cayo Santiago rhesus monkey population. Prior to 1956, monkeys on this island
      colony did not receive consistent provisions, and were reported to be in poor
      health (Rawlins and Kessler [1986] The Cayo Santiago Macaques; Albany: State
      University of New York Press). A regular provisioning program, instituted in
      August 1956, resulted in the improved health of individuals and the growth of the
      population (Rawlins and Kessler [1986] The Cayo Santiago Macaques; Albany: State
      University of New York Press). LEH, a developmental defect of enamel, is a
      sensitive indicator of systemic physiological stress (Goodman and Rose [1990]
      Yrbk. Phys. Anthropol. 33:59-110). It was therefore hypothesized that the
      prevalence of LEH would be higher in monkeys who were irregularly provisioned
      than in monkeys who experienced regular provisioning. To test this hypothesis,
      teeth were examined for LEH in a sample of 181 female rhesus monkeys. The results
      support the hypothesis: the mean number of defects was statistically
      significantly higher in the preprovisioned group than it was in the
      postprovisioned one. When LEH prevalence was assessed using only defects
      occurring on antimeric pairs, the preprovisioned group again had a higher
      prevalence than the postprovisioned one, although the difference was not
      statistically significant, most likely because of the reduced sample size. The
      results of this study indicate that changes in LEH prevalence, at least in this
      population of rhesus monkeys, are associated with changes in nutritional status.

PMID- 16617432
TI  - Evolution of genetically correlated traits: tooth size and body size in baboons.
AB  - Within a population, only phenotypic variation that is influenced by genes will
      respond to selection. Genes with pleiotropic effects are known to influence
      numerous traits, complicating our understanding of their evolution through time.
      Here we use quantitative genetic analyses to identify and estimate the shared
      genetic effects between molar size and trunk length in a pedigreed, breeding
      population of baboons housed at the Southwest National Primate Research Center.
      While crown area has a genetic correlation with trunk length, specific linear
      measurements yield different results. We find that variation in molar
      buccolingual width and trunk length is influenced by overlapping additive genetic
      effects. In contrast, mesiodistal molar length appears to be genetically
      independent of body size. This is the first study to demonstrate a significant
      genetic correlation between tooth size and body size in primates. The
      evolutionary implications are discussed.

PMID- 16617433
TI  - Khoratpithecus piriyai, a Late Miocene hominoid of Thailand.
AB  - A Khoratpithecus piriyai lower jaw corresponds to a well-preserved Late Miocene
      hominoid fossil from northeastern Thailand. Its morphology and internal
      structure, using a microcomputed tomography scan, are described and compared to
      those of other known Miocene hominoids. It originated from fluviatile sand and
      gravel deposits of a large river, and was associated with many fossil tree
      trunks, wood fragments, and large vertebrate remains. A biochronological analysis
      by using associated mammal fauna gives an estimated geological age between 9-6
      Ma. The flora indicates the occurrence of a riverine tropical forest and wide
      areas of grassland. K. piriyai displays many original characters, such as the
      great breadth of its anterior dentition, suggesting large incisors, large lower
      M3, a canine with a flat lingual wall, and symphysis structure. Several of its
      morphological derived characters are shared with the orangutan, indicating sister
      group relationship with that extant ape. This relationship is additionally
      strongly supported by the absence of anterior digastric muscle scars. These
      shared derived characters are not present in Sivapithecus, Ankarapithecus, and
      Lufengpithecus, which are therefore considered more distant relatives to the
      orangutan than Khoratpithecus. The Middle Miocene K. chiangmuanensis is older,
      displays more primitive dental characters, and shares several dental characters
      with the Late Miocene form. It is therefore interpreted as its probable ancestor.
      But its less enlarged M3 and more wrinkled enamel may suggest an even closer
      phylogenetic position to orangutan ancestors, which cannot yet be supported
      because of the incomplete fossil record. Thus Khoratpithecus represents a new
      lineage of Southeast Asian hominoids, closely related to extant great ape
      ancestors.

PMID- 16617434
TI  - Elastic properties of external cortical bone in the craniofacial skeleton of the
      rhesus monkey.
AB  - Knowledge of elastic properties and of their variation in the cortical bone of
      the craniofacial skeleton is indispensable for creating accurate finite-element
      models to explore the biomechanics and adaptation of the skull in primates. In
      this study, we measured elastic properties of the external cortex of the rhesus
      monkey craniofacial skeleton, using an ultrasonic technique. Twenty-eight
      cylindrical cortical specimens were removed from each of six craniofacial
      skeletons of adult Macaca mulatta. Thickness, density, and a set of longitudinal
      and transverse ultrasonic velocities were measured on each specimen to allow
      calculation of the elastic properties in three dimensions, according to equations
      derived from Newton's second law and Hooke's law. The axes of maximum stiffness
      were determined by fitting longitudinal velocities measured along the perimeter
      of each cortical specimen to a sinusoidal function. Results showed significant
      differences in elastic properties between different functional areas of the
      rhesus cranium, and that many sites have a consistent orientation of maximum
      stiffness among specimens. Overall, the cortical bones of the rhesus monkey skull
      can be modeled as orthotropic in many regions, and as transversely isotropic in
      some regions, e.g., the supraorbital region. There are differences from human
      crania, suggesting that structural differences in skeletal form relate to
      differences in cortical material properties across species. These differences
      also suggest that we require more comparative data on elastic properties in
      primate craniofacial skeletons to explore effectively the functional significance
      of these differences, especially when these differences are elucidated through
      modeling approaches, such as finite-element modeling.

PMID- 16617435
TI  - Test of the Lamendin aging method on two historic skeletal samples.
AB  - The Lamendin aging method involves the quantification of root translucency and
      the attachment position of the periodontal membrane. It was developed using
      recent medical-examiner specimens, and was tested on modern skeletal samples such
      as the Terry Collection (Lamendin et al. [1992] J. Forensic Sci. 37:1373-1379;
      Prince and Ubelaker [2002] J. Forensic Sci. 47:107-116). The method may be one of
      the most useful for estimating age after the mid-30s. The current study is an
      evaluation of the Lamendin criteria on two historic skeletal samples from
      Britain. Both the Christ's Church Spitalfields and St. Bride's Church collections
      represent documented skeletal samples that were interred in the 18th and 19th
      centuries. In total, 1,188 teeth from 220 adult individuals were examined from
      these two collections. The Lamendin method requires measuring total root length
      (cementoenamel junction to apex), gingival regression (cementoenamel junction to
      periodontal ligament attachment), and root translucency (root apex to maximum
      level of root translucency) on the labial surface of single-rooted teeth. Our
      results indicate that postmortem factors affect the applicability of the Lamendin
      technique to archaeological and historical samples. In particular, root
      translucency disappears with time, or is obscured by unknown postmortem
      taphonomic effects related to the length of interment or postmortem environment.
      Thirty-five percent of our sample showed no root translucency, indicating that
      caution is required when applying this method to archaeological or historical
      remains. The mean error of age estimates for Spitalfields and St. Bride's was
      higher than in the original study of Lamendin et al. ([1992] J. Forensic Sci. 37:
      1373-1379), and higher than in the test by Prince and Ubelaker ([2002] J.
      Forensic Sci. 47:107-116) of the Lamendin method on the Terry Collection.

PMID- 16617436
TI  - Quantitative analysis of human mandibular shape using three-dimensional geometric
      morphometrics.
AB  - Human mandibular morphology is often thought to reflect mainly function, and to
      be of lesser value in studies of population history. Previous descriptions of
      human mandibles showed variation in ramal height and breadth to be the strongest
      difference among recent human groups. Several mandibular traits that
      differentiate Neanderthals from modern humans include greater robusticity, a
      receding symphysis, a large retromolar space, a rounder gonial area, an
      asymmetric mandibular notch, and a posteriorly positioned mental foramen in
      Neanderthals. Nevertheless, the degree to which these differences are part of
      modern human variation and/or are related to size and function remains unclear.
      The aim of this study was to document geographic and functional patterning in the
      mandibular shape of recent humans, to assess the effects of allometry on
      mandibular form, and to quantitatively evaluate proposed "Neanderthal" mandibular
      traits through comparison with samples of geographically diverse recent humans.
      Data were collected in the form of three-dimensional coordinates of 28 landmarks.
      Unlike previous studies, this analysis found that modern human mandibular shape
      exhibits considerable geographic patterning, with some aspects of mandibular
      morphology reflecting a climatic gradient, and others, a functional
      specialization. Population history is also reflected in mandibular form, albeit
      relatively weakly. Proposed "Neanderthal" traits were found to separate
      Neanderthal from modern human mandibles successfully in the statistical analysis.
      Of these, the retromolar gap was found to be related to increased mandibular size
      in modern humans. The status of this trait as a Neanderthal autapomorphy should
      therefore be treated with caution.

PMID- 16617437
TI  - Structural characterization of Salmonella typhimurium YeaZ, an M22 O
      sialoglycoprotein endopeptidase homolog.
AB  - The Salmonella typhimurium "yeaZ" gene (StyeaZ) encodes an essential protein of
      unknown function (StYeaZ), which has previously been annotated as a putative
      homolog of the Pasteurella haemolytica M22 O-sialoglycoprotein endopeptidase Gcp.
      YeaZ has also recently been reported as the first example of an RPF from a gram
      negative bacterial species. To further characterize the properties of StYeaZ and
      the widely occurring MK-M22 family, we describe the purification, biochemical
      analysis, crystallization, and structure determination of StYeaZ. The crystal
      structure of StYeaZ reveals a classic two-lobed actin-like fold with structural
      features consistent with nucleotide binding. However, microcalorimetry
      experiments indicated that StYeaZ neither binds polyphosphates nor a wide range
      of nucleotides. Additionally, biochemical assays show that YeaZ is not an active
      O-sialoglycoprotein endopeptidase, consistent with the lack of the critical zinc
      binding motif. We present a detailed comparison of YeaZ with available structural
      homologs, the first reported structural analysis of an MK-M22 family member. The
      analysis indicates that StYeaZ has an unusual orientation of the A and B lobes
      which may require substantial relative movement or interaction with a partner
      protein in order to bind ligands. Comparison of the fold of YeaZ with that of a
      known RPF domain from a gram-positive species shows significant structural
      differences and therefore potentially distinctive RPF mechanisms for these two
      bacterial classes.

PMID- 16617438
TI  - Anatomy reports on the internet: a web-based tool for student reports on
      cadaveric findings.
AB  - The difference between the idealization of anatomy atlases and the reality of
      human cadavers often frustrates gross anatomy students. To encourage students to
      celebrate rather than protest these differences, we describe a web site ARI
      (Anatomy Reports on the Internet) that allows students to document cadaveric
      findings online with photographs and text. We used several web languages for site
      construction, including mysql, php, html, and javascript. Faculty tools allow
      instructors to upload digital images of the structures, add relevant commentary,
      view and delete images, review submitted reports, and examine database
      statistics. Student tools allow dissection groups to choose and comment on
      images, enter and edit reports, and read reports submitted by other students.
      During the first two years of the site's use (2000-2001, 2002-2003), every
      dissection group at our institution submitted at least one report. Technical
      support requests were minimal.

PMID- 16617439
TI  - The tectorial membrane: anatomical, biomechanical, and histological analysis.
AB  - There is minimal information in the literature regarding the tectorial membrane.
      Further, information in the literature regarding the anatomy and function of this
      structure is often contradictory. We performed the current study to elucidate
      further this structure's detailed anatomy, function, and histology. Thirteen
      adult cadavers underwent dissection of their tectorial membranes and detailed
      observations and measurements were made of them. Ranges of motion of the
      craniocervical junction were performed before and after transection of this
      structure. Histological analysis was performed on all membranes. The tectorial
      membrane was found to attach much more superiorly than previously described and
      was found to be firmly adherent to the cranial base and body of the axis but not
      to the posterior aspect of the odontoid process. The mean thickness of this
      membrane was found to be 1 mm. Flexion of the head made the tectorial membrane
      fully taut at 15 degrees and extension made it fully taut at 20 degrees; however,
      there was a buckling effect (redundant tectorial membrane) noted at the level of
      the odontoid process in extension. With the alar and transverse ligaments cut and
      with flexion of the head, the middle portion of this membrane was stretched over
      the odontoid process, thus acting as a "hammock" that inhibited the odontoid
      process from moving posteriorly. The tectorial membrane did not limit cervical
      flexion per se but rather helped to insure that the odontoid process did not
      impinge into the cervical canal. Lateral flexion was not found to be limited by
      this structure. Histologically, parallel collagen fibers with spindle-shaped
      fibrocytes were observed within this membrane and near its attachment to the
      posterior axis, the collagen fibers were noted to be more homogenous with larger
      non-spindled fibrocytes. At the cranial attachment of the tectorial membrane,
      multiple calcified areas were noted that interdigitated with the underlying bone.
      Also near this cephalic bony attachment, there was an increase in the number of
      elastic fibers, which were found running parallel with the surrounding Type III
      collagen fibers. The tectorial membrane was found to attach much more superiorly
      than previously described. We would propose that the tectorial membrane provides
      for a second line of defense, preventing the odontoid process from compressing
      the spinal cord and by doing so, secondarily limits movement of the
      craniocervical juncture. This hypothesis is strengthened by the finding of many
      elastic fibers in the tectorial membrane. To our knowledge, our study is the
      first to perform a detailed histological analysis of the tectorial membrane. We
      hope that these data are useful to the clinician who investigates this ligament
      of the craniocervical region.

PMID- 16617440
TI  - Three-dimensional reconstruction of the ankle by means of ultrathin slice
      plastination.
AB  - Computerized reconstruction of anatomical structures is becoming very useful for
      developing anatomical teaching modules and animations. Although databases exist
      consisting of serial sections derived from frozen cadaver material, plastination
      represents an alternate method for developing anatomical data useful for
      computerized reconstruction. Plastination is used as an excellent tool for
      studying different anatomical and clinical questions. The sheet plastination
      technique is unique because it offers the possibility to produce transparent
      slices series, which can easily be processed morphometrically. The purpose of
      this study was to describe a method for developing a computerized model of the
      human ankle using plastinated slices. This method could be applied to reconstruct
      any desired region of the human body.A human ankle was obtained, plastinated,
      sectioned, and subjected to 3D computerized reconstruction using WinSURF modeling
      system (SURFdriver Software). Qualitative observations revealed that the
      morphological features of the model were consistent with those displayed by
      typical cadaveric specimens. Morphometric analysis indicated that the model did
      not significantly differ from a sample of cadaveric specimens. These data support
      the use of plastinates for generating tissues sections useful for 3D computerized
      modeling.

PMID- 16617441
TI  - Patterns of the circumflex femoral arteries revisited.
AB  - Knowledge of variations of the circumflex femoral arteries is important when
      undertaking clinical procedures within the femoral region and in hip joint
      replacement. Since the 19th century, many different patterns have been proposed
      to classify their origins. This work studied a statistically reliable sample, the
      lower limbs of 221 embalmed human cadavers (equal right-left and approximately
      equal sex distributions), and reviewed the previous literature to propose a
      unified and simple classification that will be useful to clinicians. Statistical
      comparisons were made using the chi(2) test. The medial and lateral circumflex
      femoral arteries have been classified into three different patterns based on the
      levels of their origin. Distribution related to sex and side was also studied.
      Pattern I: Both arteries arose from the deep femoral artery (346 cases, 78.8%).
      This pattern was more frequent in females, P = 0.01. There was no significant
      difference between sides. Type Ia, medial circumflex femoral artery origin was
      proximal to the lateral circumflex femoral artery origin (53.2%); Type Ib,
      lateral circumflex femoral artery origin was proximal to medial circumflex
      femoral artery origin (23.4%); Type Ic, both arteries arose from a common trunk
      (23.4%). Pattern II: One of the arteries arose from the femoral artery and the
      other from the deep femoral artery (90 cases, 20.5%). Type IIa, the medial
      circumflex femoral artery arose from the femoral artery (77.8%) and Type IIb, the
      lateral circumflex femoral artery arose from the femoral artery (22.2%). There
      were no significant differences between sexes or sides. Pattern III: Both
      arteries arose from the femoral artery (2 cases, 0.5%). In every disposition
      there was a significantly higher prevalence of unilateral rather than bilateral
      occurrence. In one dissection the medial circumflex femoral artery was absent.
      Awareness of these variations could avoid unexpected injuries.

PMID- 16617442
TI  - Incidence of cardiovascular disease in the dissecting room: a valuable teaching
      asset.
AB  - The purpose of this study was to determine the incidence of cardiovascular
      pathology in 50 cadavers in the dissecting room of the Department of Anatomy at
      Guy's Campus, King's College, London, and to demonstrate the importance of
      dissection in teaching the anatomy of normal and pathological hearts. After
      external evaluation of each heart the four chambers were dissected and studied.
      The features noted included evidence of coronary atherosclerosis, myocardial
      infarction, variations in coronary artery anatomy, valvular disease, variations
      in left ventricular wall thickness and atrial dimensions, and atrial anomalies.
      All the hearts studied had at least one pathology. The majority had severe
      coronary atherosclerosis (44) and aortic valve pathology (23). A large number had
      left ventricular hypertrophy (13) and left atrial enlargement (9). A small number
      showed evidence of myocardial infarction (4). Anatomical anomalies were also
      found, and included persistent foramen ovale (1), three coronary arterial ostia
      (3), and anatomical variations of the orientation of the main stem of the left
      coronary artery (2). This study demonstrates that dissection is not only an
      excellent way of studying normal cardiac anatomy, but also a valuable method for
      introducing common cardiac pathologies to the medical student.

PMID- 16617443
TI  - Latin and Greek in gross anatomy.
AB  - BACKGROUND: Medical students and practitioners learn and use a vocabulary
      originating almost entirely from classical Latin and Greek languages. Previous
      generations required Latin or Greek prior to medical school, but the current
      generation does not have such requirements. Anecdotal evidence suggests that
      understanding Latin or Greek helps students to learn and practitioners to recall
      otherwise foreign terminology. This study evaluated students' familiarity with
      Latin and Greek etymologies before and after a gross anatomy course that
      incorporated etymologies into its curriculum. METHODS: First-year medical
      students at Mayo Clinic College of Medicine were taught Latin and Greek
      etymologies through lectures and handouts during their gross anatomy course. They
      took a pretest and a posttest before and after the course to assess their
      understanding of etymologies. In addition, students from all four years of
      medical school, residents, and staff physicians also took a general etymology
      quiz to assess their understanding of etymologies. RESULTS: After their gross
      anatomy course emphasizing etymologies, first-year students scored higher on the
      posttest than they did on the pretest. First-year students also reported that
      learning etymologies enhanced anatomy learning, made the experience more
      enjoyable, and proved to be less difficult than they thought it would be prior to
      the course. Medical students, residents, and staff physicians scored almost
      equally on the general etymology quiz and almost equally reported that
      etymologies enhanced learning and recalling terminology. Medical students,
      residents, and staff physicians almost equally endorsed incorporating etymologies
      into medical education. CONCLUSIONS: This study provides novel scientific
      evidence that a basic understanding of Latin and Greek etymologies enhances
      performance and comfort when learning and using medical terminology.

PMID- 16617444
TI  - Markers of airway inflammation in primary ciliary dyskinesia studied using
      exhaled breath condensate.
AB  - Macroscopically, the airways in primary ciliary dyskinesia (PCD) are inflamed and
      infected, and the eventual result is bronchiectasis. The measurement of
      noninvasive markers of inflammation in PCD may allow determination of mechanisms
      of tissue damage, and even allow monitoring of therapy. The aim of this study was
      to measure in exhaled breath condensate (EBC) of children with PCD the
      concentrations of the neutrophil chemoattractants leukotriene (LT) B4 and
      interleukin (IL)-8 and the marker of oxidative stress 8-isoprostane (8-IP), and
      to try determining whether these markers can be used to assess mechanisms of
      airway inflammation in these patients. Concentrations of LTB4, IL-8, and 8-IP in
      the EBC of 23 PCD and 11 age-matched healthy children were measured using an
      enzyme immunoassay (EIA). The children also performed spirometry and underwent
      sputum induction, the latter for differential cell count. The concentrations of 8
      IP in EBC of children with stable PCD were significantly increased compared to
      normal controls (median, 7.8 pg/ml vs. 3.1 pg/ml; P = 0.004). There was no
      difference in the median concentrations of EBC LTB4 between PCD subjects and
      healthy controls (28 pg/ml vs. 28 pg/ml; P = 0.5). IL-8 levels were below the
      detection limit of the assay, and were not analyzed further. There was no
      correlation between concentrations of either 8-IP or LTB(4) in EBC and forced
      expired volume in 1 sec in PCD children. Sputum induction was successful in 83%
      of the subjects; the median induced sputum neutrophil count was 69%
      (interquartile range, 59.3-73.6). No significant correlation was found between
      sputum neutrophils and either EBC 8-IP or LTB4 concentrations in PCD children.
      This study showed that oxidative stress, as reflected by increased exhaled 8-IP
      concentration, is increased in PCD children. The mechanism of airway neutrophilia
      is unclear, but is unlikely to be related to increased production of LTB4, at
      least in stable PCD patients.

PMID- 16617445
TI  - Determinants of airway responsiveness to adenosine 5'-monophosphate in school-age
      children with asthma.
AB  - Airway responsiveness to adenosine 5'-monophosphate (AMP) is more specific than
      that to direct stimuli for asthma diagnosis and response to treatment, but is not
      detected in all patients with asthma. This study was planned to determine
      predictive factors for responsiveness to AMP in asthmatic children between 7-16
      years old. We performed a retrospective analysis of data from 71 asthmatic
      children who were challenged by AMP in our department. All children were
      characterized by skin-prick and lung function tests and bronchial challenge with
      AMP. Data on simultaneous methacholine challenge tests were available for 46
      children, 34 of whom were also challenged with a third stimulus, exercise.
      Potential demographic factors for responsiveness to AMP were assessed by logistic
      regression analysis within the study group. The proportion of school-age children
      with asthma responsive to AMP was 39.4%. The geometric mean provocative
      concentration of AMP causing a 20% decrease in forced expiratory volume in 1 sec
      (PC20AMP) was 20.50 mg/ml (range, 0.31-377 mg/ml). There were no significant
      differences either in response to methacholine below 16 mg/ml (P = 0.66) or in
      PC20 methacholine level (P = 0.075) when we compared AMP-responsive and 
      nonresponsive children. These two groups also did not differ with respect to
      their response to exercise challenge in subgroup analysis (P = 0.34). Among
      school-age children with asthma, allergic rhinitis (P = 0.004) and sensitizaton
      to grass mix (P = 0.001), cereal mix (P = 0.003), house dust mite (P = 0.024),
      and cat (P = 0.043) were found to be more frequent in AMP-responsive children
      than the others. There was no difference in lung function test parameters between
      children responsive to AMP and the others. Grass pollen sensitization was found
      to be the only independent predictive factor for determining AMP responsiveness
      in school-age children with asthma (odds ratio, 5.65; 95% confidence interval,
      1.84-17.45; P = 0.003). In conclusion, atopic sensitization is the most important
      predictive factor for responsiveness to AMP in school-age children with asthma,
      as in adults.

PMID- 16617446
TI  - Airway function measurements and the long-term follow-up of survivors of preterm
      birth with and without chronic lung disease.
AB  - This seventh paper in a review series on different aspects of chronic lung
      disease following preterm birth focuses on the current knowledge of respiratory
      symptoms, airway function, airway hyperresponsiveness, and exercise capacity from
      childhood to adulthood. This paper further considers the long-term implications
      of these studies for both future research and clinical practice.

PMID- 16617447
TI  - Resting and exercise cardiorespiratory function in survivors of congenital
      diaphragmatic hernia.
AB  - Our objective was to study exercise capacity and cardiorespiratory response to
      exertion in survivors of congenital diaphragmatic hernia (CDH). This was a cross
      sectional cohort study of 23 CDH survivors, aged 10-16 years, and 23 gender- and
      age-matched controls. Exercise testing was performed on a cycle ergometer, with
      cardiac output measurements made using exponential CO2 rebreathing. Pretest
      cardiorespiratory assessment was done by echocardiography and pulmonary function
      testing. Statistical analysis was performed using Student's t-test, regression
      analysis, and longitudinal model computing with spatial covariance structure. No
      echocardiographic evidence for pulmonary hypertension was found at rest (right
      ventricular systolic pressures, 27 +/- 6 mmHg). Mean pulmonary artery diameter on
      the side of the CDH was significantly smaller than contralaterally, but was
      within normal range (z-score, 0 +/- 1.1 vs. 1.2 +/- 1.6, P < 0.01). Exercise
      capacity was mildly reduced in CDH compared to controls and predictive data
      (maximum workload, 77% +/- 12% vs. 91% +/- 16% of predicted, P < 0.01).
      Cardiorespiratory response to exertion was not significantly different between
      groups. In conclusion, most adolescent CDH survivors have nearly normal exercise
      capacity and cardiorespiratory response to exertion. This study may prove useful
      in comparisons with future cohorts comprising more severely affected individuals
      now surviving due to improved neonatal care.

PMID- 16617448
TI  - Airway hyperresponsiveness and body mass index: the Child Health and Environment
      Cohort Study in Hesse, Germany.
AB  - Increased body mass index has been linked to wheezing, a diagnosis of asthma, and
      morbidity. We investigated the association between body mass index (BMI),
      breastfeeding, and airway hyperresponsiveness (AHR) in 536 German schoolchildren.
      We analyzed consecutive surveys in 1994-1995 and 1997, conducted as part of the
      Child Health and Environment Cohort Study in Hesse, Germany. The questionnaire
      included questions adapted from the German version of the International Study of
      Asthma and Allergy in Childhood (ISAAC). A bronchial challenge test using 4.5%
      hypertonic saline was conducted during the 1997 survey. AHR was defined as a fall
      in forced expiratory volume in 1 sec (FEV(1)) of > or = 15%. Of 536 children who
      participated in the 1997 survey (median age, 10.3 years), 82 (15%) tested
      positive for AHR. In a multivariate analysis, there was no association between
      AHR determined at age 10 years and the highest quintile of BMI compared to the
      lowest quintile at age 4 years (odds ratio (OR), 1.4; 95% confidence interval
      (CI), 0.5-3.6), 7-8 years (OR, 0.6; 95% CI, 0.1-2.5), or 10 years (OR, 1.1; 95%
      CI, 0.2-4.3). Breastfeeding for 12 weeks or longer protected against AHR (OR,
      0.4; 95% CI, 0.2-0.9). However, when children in the highest quintile of BMI at
      age 4 years had been breastfed for 8 weeks or less, the prevalence of AHR at age
      10 years was significantly increased (27.7%, P = 0.01). In conclusion, our
      results demonstrate a protective effect of breastfeeding against AHR, and
      reinforce the need to encourage breastfeeding. Although there was no association
      between BMI and AHR, our finding of an interactive effect of high BMI and short
      breastfeeding on AHR suggests a complex etiological pathway that needs to be
      further explored.

PMID- 16617449
TI  - Bronchial responsiveness to methacholine and adenosine 5'-monophosphate in
      preschool children with bronchopulmonary dysplasia.
AB  - Bronchial hyperresponsiveness (BHR) is a characteristic feature of asthma, but it
      is also frequently present in children and adults with chronic obstructive lung
      diseases. Bronchopulmonary dysplasia (BPD) is a chronic lung disease, most
      commonly developing after mechanical ventilation and oxygen therapy in premature
      infants. BHR is usually measured by bronchial challenges, using direct or
      indirect stimuli. The aim of this study was to evaluate BHR to direct and
      indirect stimuli in young children with BPD. Methacholine and adenosine 5'
      monophosphate (AMP) bronchial challenges were performed on preschool children
      with BPD (n = 19), using a modified auscultation method. The endpoint was defined
      as the appearance of wheezing and/or oxygen desaturation. The results obtained
      were then compared with those of asthmatic (n = 25) and control (n = 23)
      preschool children. A positive response to methacholine (endpoint concentration,
      < or = 8 mg/ml) was observed in 89.5% (17/19) of patients with BPD, but a
      positive response to AMP (endpoint concentration, < or = 200 mg/ml) was observed
      only in 21.1% (4/19). All patients with asthma responded positively to
      methacholine, and most (23/25, 92.0%) of them also responded positively to AMP.
      The majority of controls were unresponsive to both challenges. BHR to
      methacholine is a frequent finding in preschool-age survivors of BPD, but is
      usually not accompanied by BHR to AMP. This suggests that most patients with BPD
      do not have the inflammatory airway response which is characteristic of asthmatic
      patients.

PMID- 16617450
TI  - Measurement of single breath-hold carbon monoxide diffusing capacity in healthy
      infants and toddlers.
AB  - We describe a method for measuring carbon monoxide diffusing capacity (DL(CO))
      and alveolar volume (V(A)) in sleeping infants, using a single 4-sec breath-hold
      technique. The breath-hold maneuver is obtained by inducing a respiratory pause
      of the respiratory system. Several inflations of the respiratory system with room
      air to a lung volume with an airway pressure of 30 cmH2O (V30) inhibit
      inspiratory effort. The respiratory system is then inflated with a test gas
      containing helium and a stable isotope of carbon monoxide (C18O), and a
      respiratory pause is maintained for 4 sec and followed by passive expiration to
      functional residual capacity. Concentrations of helium and C18O are continuously
      measured with a mass spectrometer. Twelve healthy infants between 6-22 months of
      age were evaluated. For 9 of 12 subjects, duplicate measurements of alveolar
      volume at 30 cmH2O (V(A30)) and DL(CO) were within 10%, which are the
      recommendations for older children and adults. Among these 9 subjects, values of
      V(A30) and DL(CO) increased with increasing body length (r2 = 0.82 and 0.79,
      respectively). The remaining 3 subjects had two values within 10-15%. Measurement
      of V(A) and DL(CO) with the single breath-hold technique at an elevated lung
      volume offers the potential to assess growth and development of the lung
      parenchyma early in life.

PMID- 16617451
TI  - IPPB-assisted coughing in neuromuscular disorders.
AB  - In neuromuscular disorders, reduced peak cough flows (PCFs) are considered to
      increase the risk of respiratory complications such as pneumonia or chronic
      atelectasis. Different methods were described to improve PCF. However, these
      studies were primarily carried out in adults, and there is limited information
      regarding the use and efficacy of these methods in children with respiratory
      muscle weakness. The aim of this study was to investigate whether
      hyperinsufflation with an intermittent positive-pressure breathing (IPPB) device
      is effective in cough augmentation in pediatric patients. Spirometry (forced
      inspiratory vital capacity, FIVC; forced expiratory volume in 1 sec, FEV1),
      respiratory muscle pressures (peak inspiratory pressure, PIP; peak expiratory
      pressure, PEP), and PCF were measured in 29 schoolchildren with various
      neuromuscular disorders. IPPB-assisted hyperinsufflation was taught individually
      to increase lung volumes (maximum insufflation capacity, MIC) above FIVC. The
      impact of hyperinsufflation on peak cough flow was documented. In 28/29 patients,
      IPPB-assisted hyperinsufflation enhanced FIVC from 0.68 +/- 0.40 l to an MIC of
      1.05 +/- 0.47 l (P < 0.001). Unassisted PCF was 119.0 +/- 57.7 l/min, and
      increased to 194.5 +/- 74.9 l/min (P < 0.001) in 27/29 patients. This effect was
      similar in young patients (ages 6-10 years) and older patients (aged >10 years).
      Augmentation of lung volumes from FIVC to MIC correlated with an increase of PCF
      (R = 0.42, P < 0.05). IPPB-assisted hyperinsufflation improves PCF in pediatric
      neuromuscular disorders. The results suggest that this technique can be used to
      improve clearance of airway secretions and therefore reduce respiratory morbidity
      in children with NMD.

PMID- 16617452
TI  - Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist,
      prevents hyperoxia-induced neonatal rat lung injury in vivo.
AB  - Molecular disruption of homeostatic alveolar epithelial-mesenchymal interactions
      results in transdifferentiation of alveolar interstitial lipofibroblasts to
      myofibroblasts. Although this process was suggested to be a central molecular
      event in the pathogenesis of bronchopulmonary dysplasia (BPD), so far it has been
      only demonstrated in vitro; whether it also occurs in vivo is unknown. Our
      objectives were to determine if exposure to hyperoxia results in pulmonary
      alveolar lipo-to-myofibroblast transdifferentiation in vivo, and whether
      treatment with a potent peroxisome proliferator-activated receptor gamma
      (PPARgamma) (the key lipogenic fibroblast nuclear transcription factor) agonist,
      rosiglitazone, prevents this process. Newborn Sprague Dawley rat pups were
      exposed to control (21% O2), hyperoxia alone (95% O2 for 24 hr), or hyperoxia
      with rosiglitazone (95% O2 for 24 hr + rosiglitazone, 3 mg/kg, administered
      intraperitoneally) conditions. Subsequently, pups were sacrificed, and lung
      tissue was analyzed by morphometry, and by reverse transcription-polymerase chain
      reaction, Western hybridization, and immunohistochemistry for the expression of
      key lipogenic and myogenic markers. We observed a significant decrease in the
      expression of lipogenic markers, and a significant increase in the expression of
      myogenic markers in the hyperoxia-alone group. These hyperoxia-induced
      morphologic, molecular, and immunohistochemical changes were almost completely
      prevented by rosiglitazone. This is the first evidence of in vivo lipo-to
      myofibroblast transdifferentiation and its almost complete prevention by
      rosiglitazone, prompting us to conclude that administration of PPARgamma agonists
      may be a novel, effective strategy to prevent the hyperoxia-induced lung
      molecular injury that has been implicated in the pathogenesis of BPD.

PMID- 16617453
TI  - Respiratory function at age 8-9 years in extremely low birthweight/very preterm
      children born in Victoria in 1991-1992.
AB  - Our aim was to determine respiratory function at 8 years of age in extremely low
      birth weight (ELBW; birth weight, < 1,000 g)/very preterm (< 28 weeks of
      gestation) children born in the 1990s compared with normal birth weight (NBW;
      birth weight, >2,499 g) controls. The ELBW/very preterm subjects comprised 298
      consecutive survivors with either birth weight < 1,000 g or gestational age < 28
      weeks born in the state of Victoria during 1991-1992. Controls comprised 262
      randomly selected NBW survivors. Respiratory function was measured on 81%
      (240/298) of the ELBW/very preterm children and 79% (208/262) of the NBW
      controls. Respiratory function variables reflecting airflow were substantially
      diminished in ELBW/very preterm children compared with NBW controls. Moreover,
      the proportions with clinically important reductions in airflow were higher in
      the ELBW/very preterm group (e.g., forced expired volume in 1 sec, < 75%;
      ELBW/very preterm, 19.7%; NBW, 2.4%; P < 0.0001). Within the ELBW/very preterm
      group, children who had bronchopulmonary dysplasia (BPD) in the newborn period
      and those who had later asthma had significantly reduced respiratory function in
      variables reflecting airflow. In conclusion, the abnormalities in respiratory
      function in ELBW/very preterm children compared with NBW subjects described in
      the presurfactant era persisted in the 1990s, especially in those who had BPD in
      the newborn period.

PMID- 16617454
TI  - Airway inflammation in asymptomatic children with episodic wheeze.
AB  - Airway pathologies have been comprehensively researched in adult asthma, but in
      children, the extent of airway inflammation associated with episodic wheeze,
      often diagnosed as asthma, has not been fully characterized. It is not clear
      whether persistent airway inflammation is present in the absence of wheezing
      symptoms, and there is controversy regarding the role of age and atopy. This
      study assessed cellular and cytokine markers of airway inflammation in
      asymptomatic children with a history of episodic wheeze. Children with a history
      of episodic wheeze and cough (study group) and nonasthmatic patients requiring
      elective surgery (control group) were recruited. All subjects in the study group
      had a history of significant episodic wheezing (>2 episodes per year), and used
      only as-needed beta-agonist treatment. Bronchoalveolar lavage (BAL) was obtained
      using bronchoscopic lavage (study group) and nonbronchoscopic lavage (control
      group). Differential cell counts of BAL and flow cytometry were performed to
      identify T-lymphocyte phenotypes, and intracellular cytokine profiles were
      measured after phorbol-12-myristate 13-acetate (PMA) stimulation of BAL fluid T
      cells. Twenty-one children with a history of 2-12 episodes of wheeze per year and
      21 nonasthmatic subjects without respiratory symptoms were recruited. Study and
      control subjects were matched for age (median age, 5 years) and demographic
      characteristics. Study subjects had higher IgE levels, but their measurements
      were still within normal range. No significant differences in BAL differential
      cell counts were noted, and in both groups, the majority of T-cells were CD3+
      CD8+, with a median CD4:CD8 ratio of 0.6. There was no significant difference in
      T-cell expression of the activation markers HLA-DR and CD25 (IL-2 receptor), or
      in PMA-induced production of the intracellular cytokines IFN-gamma, IL-2, IL-4,
      IL-5, and IL-10. The results of this study suggest that significant T-cell-driven
      airway inflammation is absent in mild or nonatopic, asymptomatic children of this
      age group who have episodic wheeze. Our findings support asthma management
      guidelines that do not recommend long-term treatment of this group of patients
      with anti-inflammatory medications.

PMID- 16617455
TI  - Association of improved pulmonary phenotype in Irish cystic fibrosis patients
      with a 3' enhancer polymorphism in alpha-1-antitrypsin.
AB  - Modifier genes other than CFTR are thought to influence lung disease phenotype in
      cystic fibrosis (CF). In this study, we investigated the relationship between a
      polymorphism (1237 G --> A) in the 3' enhancer region of the alpha-1-antitrypsin
      (AAT) gene and pulmonary disease severity in 320 CF patients recruited from two
      independent adult referral centers in Ireland, and evaluated the in vivo effect
      of the polymorphism on AAT levels during acute infection. When corrected for
      confounding variables, the polymorphism was found to make a small but significant
      contribution to variance in percent predicted forced expired volume in 1 sec
      (FEV1) (1.1%, P = 0.05), with possession of the A allele being associated with
      better pulmonary function (AA/AG genotype: percent predicted FEV1, 70.8 +/- 3.9;
      GG genotype: percent predicted FEV1, 62.0 +/- 1.4). As would be expected of a
      modifier effect, the influence of the polymorphism was more marked in patient
      groups traditionally associated with more severe lung disease, contributing 3.2%
      (P = 0.033) to the variance in percent predicted FEV1 in patients homozygous for
      DF508, 3.3% (P = 0.007) to those infected with Pseudomonas aeruginosa, and 3% (P
      = 0.024) in female patients. In each instance, a positive association between
      possession of the A variant and higher percent predicted FEV1 was observed. We
      did not, however, find any evidence that possession of the A allele effected
      upregulation of AAT during acute infection in vivo. This lack of a demonstrable
      functional effect in vivo suggests that the polymorphism is a marker for a
      modifying effect on pulmonary phenotype in the Irish CF population by a mechanism
      that is yet to be explained.

PMID- 16617456
TI  - Horseshoe lung and facio-auriculo-vertebral sequence: a previously unreported
      association.
AB  - We describe a case of horseshoe lung in an infant with facio-auriculo-vertebral
      (FAV) sequence that included mild hemifacial microsomia, ear anomalies, a missing
      left rib, left hemivertebrae (T2-T4), and complex congenital heart disease. Of
      the approximately 40 cases of horseshoe lung described since 1962, most are
      reported in association with scimitar syndrome, and only four reported cases were
      associated with left lung hypoplasia. None of these cases included malformations
      consistent with a diagnosis of FAV sequence.

PMID- 16617457
TI  - Carpal anomalies.

PMID- 16617458
TI  - Cavernous sinus anatomy as a basis for interpretation of the clinical picture and
      radiological investigations in a case of Entomophthorales infection.
AB  - Several cranial nerves traverse the cavernous sinus producing the typical symptom
      complex seen during cavernous venous sinus thrombosis in Mucorales infection.
      Fungi of the order Entomophthorales display different pathological and
      histological characteristics although belonging to the same class of fungi. A
      case is presented, wherein the anatomy of the cavernous sinus forms the basis in
      explaining the presenting symptoms of a patient with Entomophthorales infection.
      The anatomical explanation for the presenting neurological symptoms is confirmed
      by radiological investigations and further supports the diagnosis of
      Entomophthorales infection.

PMID- 16617459
TI  - Anatomical instruction and training for professionalism from the 19th to the 21st
      centuries.
AB  - For most of the 19th century, anatomists in the United States saw the affective,
      emotional aspects of human dissection as salient ingredients in professional
      formation. Professionalism (or "character") signified medical integrity and
      guaranteed correct professional conduct. As gross anatomy came under siege in the
      late-19th and early-20th centuries, crowded out of medical curricula by the new
      experimental sciences, medical educators rethought what it was that dissecting a
      human body stood to give medical students. As they embraced a new understanding
      of professionalism premised on an allegiance to science, anatomists celebrated
      the habits of mind and sensibility to scientific investigation that could be
      acquired at the dissecting table. One consequence was a deliberate distancing of
      gross anatomy from the "art of medicine," and with it a de facto suppression of
      attention to the affective components of human dissection. During this period in
      the opening decades of the 20th century, the norm of silence about the emotional
      dimensions of dissection was set in place. The confluence of various movements by
      the 1960s and 1970s both revived attention to the emotional experience of
      dissection and sparked a renewed discussion about the relationship between the
      affective components of learning anatomy and the professional formation of future
      healers. There is a need to balance the tension between the "affective" and
      "scientific" aspects of anatomy, and by extension the tension between the "art"
      and "science" of medical practice. One method is to use small-group "learning
      societies" as a means to cultivate and meld both dimensions of the professional
      ethic.

PMID- 16617460
TI  - Artificial rearing alters the response of rats to natural and drug-mediated
      rewards.
AB  - Artificial rearing (AR) of infant rats permits precise control over key features
      of the early environment without maternal influence. The present study examined
      the behavioral response of AR rats towards natural and drug-mediated rewards, as
      well as their exploratory and affective behaviors. Adolescent AR rats showed
      increased preference for sucrose consumption relative to chow and demonstrated
      greater activity in the open field and in the elevated plus-maze compared to
      maternally reared (MR) rats. With respect to measures of emotionality, AR rats
      showed enhanced avoidance of the open arms of the plus-maze, indicating increased
      anxiety, but they did not differ from MR rats in exploring the center of the open
      field. Adult AR rats displayed a stronger conditioned response to morphine in a
      place preference test. These findings support the potential of the AR model to
      contribute to understanding the role of early experience in the development of
      behavioral motivation.

PMID- 16617462
TI  - Potential interactions among linguistic, autonomic, and motor factors in speech.
AB  - Though anecdotal reports link certain speech disorders to increases in autonomic
      arousal, few studies have described the relationship between arousal and speech
      processes. Additionally, it is unclear how increases in arousal may interact with
      other cognitive-linguistic processes to affect speech motor control. In this
      experiment we examine potential interactions between autonomic arousal,
      linguistic processing, and speech motor coordination in adults and children.
      Autonomic responses (heart rate, finger pulse volume, tonic skin conductance, and
      phasic skin conductance) were recorded simultaneously with upper and lower lip
      movements during speech. The lip aperture variability (LA variability index)
      across multiple repetitions of sentences that varied in length and syntactic
      complexity was calculated under low- and high-arousal conditions. High arousal
      conditions were elicited by performance of the Stroop color word task. Children
      had significantly higher lip aperture variability index values across all
      speaking tasks, indicating more variable speech motor coordination. Increases in
      syntactic complexity and utterance length were associated with increases in
      speech motor coordination variability in both speaker groups. There was a
      significant effect of Stroop task, which produced increases in autonomic arousal
      and increased speech motor variability in both adults and children. These results
      provide novel evidence that high arousal levels can influence speech motor
      control in both adults and children.

PMID- 16617464
TI  - What is so critical?: a commentary on the reexamination of critical periods.

PMID- 16617466
TI  - The computational modeling of sensitive periods.

PMID- 16617467
TI  - Effects of prenatal visual stimulation on growth and heart rate in bobwhite quail
      (Colinus virginianus).
AB  - This study examined the effects of prenatal visual stimulation on bobwhite quail
      embryos' growth and heart rate. No differences in growth rate were found between
      embryos exposed to visual stimulation during the late prenatal period and control
      embryos. Embryos exposed to visual stimulation throughout incubation maintained
      lower heart rates in response to visual stimulation than did naive embryos. In a
      subsequent experiment, naive embryos that underwent an egg-opening procedure
      exhibited heart rates that were lower than embryos measured in intact eggshells.
      Embryos in opened eggs maintained lower heart rates than comparison embryos
      across time; however, a less invasive egg-opening procedure led to a quicker
      heart rate recovery than did a more invasive egg-opening procedure. These
      findings indicate that prenatal heart rate responses may be mediated by multiple
      features of the organism's developmental context, including intensity and
      duration of sensory stimulation.

PMID- 16617468
TI  - Perception of audiovisual rhythm and its invariance in 4- to 10-month-old
      infants.
AB  - This study investigated the perception of complex audiovisual rhythmic patterns
      in 4-, 6-, 8-, and 10-month-old human infants. In Experiment 1, we first
      habituated infants to an event in which an object could be seen and heard
      bouncing in a rhythmic fashion. We then tested them to determine if they would
      detect a relative temporal pattern change produced by rearranging the
      intrapattern intervals. Regardless of age, infants successfully detected the
      pattern change. In Experiment 2, we asked whether infants also can extract
      rhythmic pattern invariance amid tempo variations. Thus, we first habituated
      infants to a particular rhythmic pattern but this time varying in its tempo of
      presentation across trials. We then administered one test trial in which a novel
      rhythm was presented at a familiar tempo and another test trial in which a
      familiar rhythm was presented at a novel tempo. Infants detected both types of
      changes indicating that they perceived the invariant rhythm and that they did so
      despite the fact that they also detected the varying tempo. Overall, the findings
      demonstrate that infants between 4 and 10 months of age can perceive and
      discriminate complex audiovisual temporal patterns on the basis of relative
      temporal differences and that they also can learn the invariant nature of such
      patterns.

PMID- 16617470
TI  - Trichopus zeylanicus combats fatigue without amphetamine-mimetic activity.
AB  - Chronic fatigue is a complex and little understood symptom for which there is no
      safe and effective pharmacotherapy. The present study was conducted to
      investigate the effectiveness of Trichopus zeylanicus whole plant powder on
      fatigue in young Sprague Dawley rats, and aged normal and long-living mutant Ames
      dwarf mice. Fatigue was evaluated by subjecting the animals to a forced swim
      test. Trichopus zeylanicus (250 and 500 mg/kg) treated young Sprague-Dawley rats
      resisted fatigue at a significant level (p < 0.005) compared with controls by an
      extended swim time in the forced swim test. Oral Trichopus zeylanicus (500 mg/kg)
      treatment for 2 weeks significantly increased the mobility time in the aged
      mutant (p < 0.05) and normal mice (p < 0.01) and significantly increased the swim
      time in the forced swim test in the aged normal mice (p < 0.05). Amphetamine
      mimetic activity in Trichopus zeylanicus was excluded by suitable tests. These
      results show that Trichopus zeylanicus whole plant powder has anti-fatigue
      effects in young Sprague-Dawley rats and aged normal and mutant Ames dwarf mice
      providing scientific evidence for the Kani tribal practice in India.

PMID- 16617472
TI  - Preface.

PMID- 16617471
TI  - Detection and characterization by high-performance liquid chromatography and mass
      spectrometry of two truncated goat alphas2-caseins.
AB  - The identification and characterization of truncated forms of goat alphas2-Cn
      variants A and E are reported. The two proteins, which have experimental Mr
      values of 24 183 and 24 227 Da, were detected as minor components in a goat milk
      sample from an autochthonous breed of southern Italy, 'Rossa Mediterranea', by
      reversed-phase high-performance liquid chromatography/electrospray ionization
      mass spectrometry (RP-HPLC/ESI-MS). Characterization of the amino acid sequences,
      performed by coupling trypsin digestion with matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS), RP-HPLC/ESI-MS and tandem
      mass spectrometry (MS/MS), demonstrated that the polypeptide chains correspond to
      the 1-204 sequence of mature alphas2-Cn variant A (component with Mr of 24 183
      Da) and E (component with Mr of 24 227 Da), respectively. These components seem
      to be the product of a differential splicing of pre-messenger RNA during the
      translation process of the alphas2-Cn variants A and E.

PMID- 16617473
TI  - An efficient method for scoring base pair interactions.
AB  - A simple method is described for speeding up the computation of base pairing
      interractions. It is especially effective on microcomputers.

PMID- 16617474
TI  - Binding of 16S rRNA to chloroplast 30S ribosomal proteins blotted on
      nitrocellulose.
AB  - Protein-RNA associations were studied by a method using proteins blotted on a
      nitrocellulose sheet. This method was assayed with Escherichia Coli 30S ribosomal
      components. In stringent conditions (300 mM NaCl or 20 degrees C) only 9 E. coli
      ribosomal proteins strongly bound to the 16S rRNA: S4, S5, S7, S9, S12, S13, S14,
      S19, S20. 8 of these proteins have been previously found to bind independently to
      the 16S rRNA. The same method was applied to determine protein-RNA interactions
      in spinach chloroplast 30S ribosomal subunits. A set of only 7 proteins was bound
      to chloroplast rRNA in stringent conditions: chloroplast S6, S10, S11, S14, S15,
      S17 and S22. They also bound to E. coli 16S rRNA. This set includes 4 chloroplast
      synthesized proteins: S6, S11, S15 and S22. The core particles obtained after
      treatment by LiCl of chloroplast 30S ribosomal subunit contained 3 proteins (S6,
      S10 and S14) which are included in the set of 7 binding proteins. This set of
      proteins probably play a part in the early steps of the assembly of the
      chloroplast 30S ribosomal subunit.

PMID- 16617475
TI  - Aminoacyl RNA domain of turnip yellow mosaic virus Val-RNA interacting with
      elongation factor Tu.
AB  - Turnip yellow mosaic virus (TYMV) Val-RNA forms a complex with the peptide
      elongation factor Tu (EF-Tu) in the presence of GTP: the Val-RNA is protected by
      EF-Tu.GTP from non-enzymatic deacylation and nuclease digestion. The
      determination of the length of the shortest TYMV Val-RNA fragment that binds EF
      Tu.GTP leads us to conclude that the valylated aminoacyl RNA domain equivalent in
      tRNAs to the continuous helix formed by the acceptor stem and the T arm is
      sufficient for complex formation. Since the aminoacyl RNA domain is also
      sufficient for adenylation by the ATP(CTP):tRNA nucleotidyltransferase, an
      analogy can be drawn between these two tRNA-specific proteins.

PMID- 16617476
TI  - Preface.

PMID- 16617478
TI  - Preface.

PMID- 16617477
TI  - Preface.

PMID- 16617479
TI  - A new system for direct submission of data to the nucleotide sequence data banks.

PMID- 16617480
TI  - NAR's new requirement for data submission to the EMBL data library: information
      for authors.

PMID- 16617481
TI  - Introduction.

PMID- 16617482
TI  - Preface.

PMID- 16617483
TI  - Potential role of proteolysis in the control of UvrABC incision.
AB  - UvrB is specifically proteolyzed in Escherichia coli cell extracts to UvrB*.
      UvrB* is capable of interacting with UvrA in an aparently similar manner to the
      UvrB, however UvrB* is defective in the DNA strand displacement activity normally
      displayed by UvrAB. Whereas the binding of UvrC to a UvrAB-DNA complex leads to
      DNA incision and persistence of a stable post-incision protein-DNA complex, the
      binding of UvrC to UvrAB* leads to dissociation of the protein complex and no DNA
      incision is seen. The factor which stimulates this proteolysis has been partially
      purified and its substrate specificity has been examined. The protease factor is
      induced by "stress" and is under control of the htpR gene. The potential role of
      this proteolysis in the regulation of levels of active repair enzymes in the cell
      is discussed.

PMID- 16617485
TI  - Editorial.

PMID- 16617484
TI  - Involvement of a cryptic ATPase activity of UvrB and its proteolysis product,
      UvrB* in DNA repair.
AB  - The incision of damaged DNA by the Escherichia coli UvrABC endonuclease requires
      ATP hydrolysis. Although the deduced sequence of the UvrB protein suggests a
      putative ATP binding site, no nucleoside triphosphatase activity is demonstrable
      with the purified UvrB protein. The UvrB protein is specifically proteolyzed in
      E. coli cell extracts to yield a 70 kD fragment, referred to as UvrB*, which has
      been purified and is shown to possess a single-strand DNA dependent ATPase
      activity. Substrate specificity and kinetic analyses of UvrB* catalyzed
      nucleotide hydrolysis indicate that the stimulation in DNA dependent ATPase
      activity following formation of the UvrAB complex results from the activation of
      the normally sequestered UvrB associated ATPase. Using nucleotide analogues, it
      can be shown that this activity is essential to the DNA incision reaction carried
      out by the UvrABC complex.

PMID- 16617487
TI  - Editorial: distribution of research materials.

PMID- 16617486
TI  - A second Xenopus immunoglobulin heavy chain constant region isotype gene.

PMID- 16617488
TI  - Editorial.

PMID- 16617490
TI  - DNA sequence policy Editorial.

PMID- 16617489
TI  - DNA sequence policy Editorial.

PMID- 16617491
TI  - Deposition of atomic coordinates and other data for crystal structures Notes for
      Authors.

PMID- 16617492
TI  - Deposition of atomic coordinates and other data for crystal structures Notes for
      Authors.

PMID- 16617493
TI  - New policy on methods within full papers.

PMID- 16617494
TI  - New policy on methods within full papers.

PMID- 16617495
TI  - Deposition of atomic coordinates and other data for crystal structures Notes for
      Authors.

PMID- 16617496
TI  - Deposition of atomic coordinates and other data for crystal structures.

PMID- 16617497
TI  - Competition of aminoacyl-tRNA synthetases for tRNA ensures the accuracy of
      aminoacylation.
AB  - The accuracy of protein biosynthesis rests on the high fidelity with which
      aminoacyl-tRNA synthetases discriminate between tRNAs. Correct aminoacylation
      depends not only on identity elements (nucleotides in certain positions) in tRNA
      (1), but also on competition between different synthetases for a given tRNA (2).
      Here we describe in vivo and in vitro experiments which demonstrate how
      variations in the levels of synthetases and tRNA affect the accuracy of
      aminoacylation. We show in vivo that concurrent overexpression of Escherichia
      coli tyrosyl-tRNA synthetase abolishes misacylation of supF tRNA(Tyr) with
      glutamine in vivo by overproduced glutaminyl-tRNA synthetase. In an in vitro
      competition assay, we have confirmed that the overproduction mischarging
      phenomenon observed in vivo is due to competition between the synthetases at the
      level of aminoacylation. Likewise, we have been able to examine the role
      competition plays in the identity of a non-suppressor tRNA of ambiguous identity,
      tRNA(Glu). Finally, with this assay, we show that the identity of a tRNA and the
      accuracy with which it is recognized depend on the relative affinities of the
      synthetases for the tRNA. The in vitro competition assay represents a general
      method of obtaining qualitative information on tRNA identity in a competitive
      environment (usually only found in vivo) during a defined step in protein
      biosynthesis, aminoacylation. In addition, we show that the discriminator base
      (position 73) and the first base of the anticodon are important for recognition
      by E. coli tyrosyl-tRNA synthetase.

PMID- 16617498
TI  - Editorial.

PMID- 16617499
TI  - Editorial.

PMID- 16617500
TI  - Editorial.

PMID- 16617502
TI  - Editorial.

PMID- 16617501
TI  - Conserved sequence motif DPPY in region IV of the phage T4 Dam DNA-[N-adenine]
      methyltransferase is important for S-adenosyl-L-methionine binding.
AB  - Comparison of the deduced amino acid sequences of DNA-[N(6)-adenine]
      methyltransferases has revealed several conserved regions. All of these enzymes
      contain a DPPY-motif, or a variant of it. By site-directed mutagenesis of a
      cloned T4 dam gene, we have altered the first proline residue in this motif
      (located in conserved region IV of the T4 Dam-MTase) to alanine or threonine. The
      mutant enzymic forms, P172A and P172T, were overproduced and purified. Kinetic
      studies showed that compared to the wild-type (wt) the two mutant enzymic forms
      had: (i) an increased (6 and 23-fold, respectively) K(m) for substrate, S
      adenosyl-methionine (AdoMet) and an increased (6 and 23-fold) K(i) for product, S
      adenosyl-homocysteine (AdoHcy); (ii) a slightly reduced (1.5 and 3-fold lower)
      k(cat); (iii) a strongly reduced k(cat)/K(m) (AdoMet) (10 and 80-fold); and (iv)
      the same K(m) for substrate DNA. Equilibrium dialysis studies showed that the
      mutant enzymes had a reduced (3 and 7-fold lower) K(a) for AdoMet; all forms
      bound two molecules of AdoMet. Taken together these data indicate that the P172A
      and P172T alterations resulted primarily in a reduced affinity for AdoMet. This
      suggests that the DPPY-motif is important for AdoMet-binding, and that region IV
      contains an AdoMet-binding site.

PMID- 16617503
TI  - Editorial.

PMID- 16617504
TI  - Editorial.

PMID- 16617506
TI  - Editorial.

PMID- 16617505
TI  - Short reports.

PMID- 16617507
TI  - Editorial.

PMID- 16617508
TI  - Short reports.

PMID- 16617510
TI  - Short reports.

PMID- 16617509
TI  - Editorial.

PMID- 16617511
TI  - Editorial.

PMID- 16617512
TI  - Editorial.

PMID- 16617513
TI  - Nucleic acids chemistry.

PMID- 16617514
TI  - A nomenclature of junctions and branchpoints in nucleic acids.

PMID- 16617516
TI  - Average out-of-pocket health care costs for families hit 35 percent of income.

PMID- 16617515
TI  - The phycocyanin-associated rod linker proteins of the phycobilisome of
      Gloeobacter violaceus PCC 7421 contain unusually located rod-capping domains.
AB  - Gloeobacter violaceus PCC 7421 is a unique cyanobacterium that has no thylakoids
      and whose genome has been sequenced [Y. Nakamura, T. Kaneko, S. Sato, M. Mimuro,
      H. Miyashita, T. Tsuchiya, S. Sasamoto, A. Watanabe, K. Kawashima, Y. Kishida, C.
      Kiyokawa, M. Kohara, M. Matsumoto, A. Matsuno, N. Nakazaki, S. Shimpo, C.
      Takeuchi, M. Yamada, S. Tabata, Complete Genome Structure of Gloeobacter
      violaceus PCC 7421, a cyanobacterium that lacks thylakoids. DNA Research 10
      (2003) 137-145]. Phycobilisomes of G. violaceus were isolated and analyzed by SDS
      PAGE followed by N-terminal sequencing. Three rod-linker subunits (CpeC, CpeD and
      CpeE) were identified as predicted from the genome sequence. The cpcC1 and cpcC2
      genes at order locus named (OLN) glr0950 and gll 3219 encoding phycocyanin
      associated linker proteins from G. violaceus are 56 and 55 amino acids longer at
      the N-terminus than the open reading frame proposed in the genome. The two amino
      acid extensions showed a 66% identity to one another. Also, the N-terminal
      extensions of these sequences were similar to domains in both the rod-capping
      linker protein CpcD2 and to the C-terminus domain of the phycoerythrin-associated
      linker protein CpeC. These domains are not only unusual in their N-terminal
      location, but are unusual in that they are more closely related in sequence
      similarity to the C-terminus domain of the phycoerythrin-associated linker, CpeC
      of G. violaceus, than to the C-terminus domain of phycocyanin-associated linker
      CpcC in other cyanobacteria. These linker proteins with unique special domains
      are indicators of the unusual structure of the phycobilisomes of G. violaceus.

PMID- 16617517
TI  - Emergency physicians present 10-point plan to avoid mass casualties from flu
      pandemic or other disaster.

PMID- 16617518
TI  - What's the agenda? Abstinence-only education programs.

PMID- 16617519
TI  - An unfulfilled promise of the Medicaid Act: enforcing Medicaid recipients' right
      to health care.

PMID- 16617520
TI  - Rethinking autonomy in long term care.

PMID- 16617521
TI  - Technology and the nursing shortage.

PMID- 16617522
TI  - White paper on global nursing and health: a brief.

PMID- 16617523
TI  - One hundred years of the Nobel Science Prizes.

PMID- 16617524
TI  - Games editors played or knowledge readers made?

PMID- 16617525
TI  - Paroxetine may increase risk for congenital malformations.

PMID- 16617526
TI  - Competency to refuse psychotropic medication: three alternatives to the law's
      cognitive standard.

PMID- 16617527
TI  - Silencing the different voice: competence, feminist theory and law.

PMID- 16617528
TI  - A short history of the next thirty years: genetic testing, clinical care and
      personal choices.

PMID- 16617529
TI  - Genetics in the courtroom.

PMID- 16617530
TI  - Genetic discrimination: meeting the challenges of an emerging issue.

PMID- 16617531
TI  - Playing God? Owning God?--Patenting and the human genome.

PMID- 16617532
TI  - Patentable subject matter, TRIPS and the European Biotechnology Directive:
      Australia and patenting human genes.

PMID- 16617533
TI  - Maintaining community trust in biomedical research involving humans.

PMID- 16617534
TI  - Bioscience, community expectations and the law.

PMID- 16617535
TI  - Essentially Yours: The Protection of Human Genetic Information in Australia--the
      impact on clinical practice and the 'new genetics'.

PMID- 16617536
TI  - And baby makes three--or four, or five, or six: redefining the family after the
      reprotech revolution.

PMID- 16617537
TI  - Constitutionality of recognizing multiple parental rights in the surrogacy
      context.

PMID- 16617538
TI  - A practical analysis of the constitutional and legal infirmities of Norplant as a
      condition of probation.

PMID- 16617539
TI  - Diagnosis of serous neuroretinal detachments of the macula in severe preeclamptic
      patients with optical coherence tomography.
AB  - OBJECTIVE: Visual symptoms are common in patients with preeclampsia, and are
      caused by various underlying pathological changes in the retina. Blurred vision
      may be one of these symptoms. We describe three cases in which the underlying
      retinal pathology of blurred vision was clarified using optical coherence
      tomography (OCT), a novel, non-invasive ophthalmic imaging technique that
      provides micrometer-scale resolution images of the human retina. METHODS: Three
      patients with preeclampsia complained of blurred vision postpartum. In all cases,
      ophthalmoscopy was performed at the bedside, followed by the assessment of best
      corrected visual acuity, slit-lamp biomicroscopy, fluorescein angiography (FLA),
      and OCT. In all cases, the presence of central visual defects was examined by an
      Amsler-grid. RESULTS: In one case, the symptoms were bilateral. In all affected
      eyes, the patients complained of a relative central scotoma. Ophthalmoscopy
      showed edema in the affected maculae, while OCT examination clarified a serous
      neurosensory detachment of the macula. In one case, a neurosensory detachment was
      also detected in the papillomacular region of a fellow eye with no symptoms. In
      two cases, FLA was performed, but only in one case could we detect late leakage
      and subretinal exudates. The serous detachments observed showed total resolution
      in all cases within 5 to 10 weeks, with restoration of visual acuity. CONCLUSION:
      In patients with preeclampsia, OCT may provide a useful method for the precise
      assessment of retinal changes, distinguishing retinal edema from serous
      neurosensory detachments. This finding may help to clarify the pathophysiological
      circulatory changes seen in preeclampsia.

PMID- 16617540
TI  - Encouraging reflection in practice.

PMID- 16617541
TI  - Check my nodes please--all of them.

PMID- 16617542
TI  - Target the brain to get the gain?

PMID- 16617543
TI  - Chronic diarrhea, HIV, and honeybees.

PMID- 16617544
TI  - The changing nature of adolescence in the Kassena-Nankana District of northern
      Ghana.
AB  - This study reports the results of a primarily qualitative investigation of
      adolescent reproductive behavior in the Kassena-Nankana District, an isolated
      rural area in northern Ghana, where traditional patterns of marriage, family
      formation, and social organization persist. The study is based on in-depth
      interviews and focus-group discussions with adolescents, parents, chiefs,
      traditional leaders, youth leaders, and health workers, supplemented by
      quantitative data from the 1996 wave of a panel survey of women of reproductive
      age conducted by the Navrongo Health Research Centre. The social environment that
      adolescent boys and girls in the Kassena-Nankana District encounter and its links
      to reproductive behavior are described. The principal question is whether even in
      this remote rural area, the social environment has been altered in ways that have
      undermined traditional sexual and reproductive patterns. The survey data indicate
      a considerable increase in girls' education and the beginning of a decline in the
      incidence of early marriage. The qualitative data suggest that social
      institutions, systems, and practices such as female circumcision that previously
      structured the lives of adolescent boys and girls have eroded, leading to an
      apparent increase in premarital sexual activity.

PMID- 16617545
TI  - A study of field-based methods for diagnosing reproductive tract infections in
      rural Yunnan Province, China.
AB  - Reproductive tract infections are a significant cause of poor health among rural
      Chinese women. This study assesses the accuracy of simple, field-based methods of
      diagnosing five reproductive tract infections (trichomonas, candida, bacterial
      vaginosis, gonorrhea, and chlamydia) in two rural Chinese counties, using "gold
      standard" laboratory diagnosis as the reference. Self-reported symptoms and
      clinical examination proved inadequate for making accurate diagnoses, because
      many infected women show no symptoms or are infected with two or more conditions.
      The use of simple tests such as KOH staining, wet mount, Gram's stain, and pH of
      discharge greatly improved diagnostic accuracy, especially for candida and
      trichomonas, the two most common infections. Promoting the use of such diagnostic
      approaches by rural Chinese medical and family planning health providers would
      reduce the prevalence and severity of these preventable and easily treated
      infections.

PMID- 16617546
TI  - The impact of the family planning supply environment on contraceptive intentions
      and use in Morocco.
AB  - Although the extent to which organized family planning programs influence
      reproductive preferences remains a subject of debate, most observers would grant
      that such programs play a key role in helping individuals to realize their
      contraceptive and reproductive intentions. However, few prior studies have
      quantified the magnitude of this facilitating or enabling effect of family
      planning services, given existing demand for contraception. This study takes
      advantage of panel survey data and linked information on the supply environment
      for family planning services in Morocco in order to bridge this research gap. In
      the analysis, contraceptive use during the 1992-95 period is related to
      contraceptive intentions in 1992; individual-, household-, and community-level
      determinants of contraceptive behavior; and family planning supply factors.
      Estimation procedures are used that control for unobserved joint determinants of
      contraceptive intentions and use. Evidence of a significant enabling or
      facilitating role of family planning services is found, and the results also
      suggest that family planning program factors influence contraceptive intentions
      in important ways.

PMID- 16617547
TI  - Integrated maternal and infant health care in the postpartum period in a poor
      neighborhood in Santiago, Chile.
AB  - An integrated postpartum health-care program was established by the Consultorio
      San Luis de Huechuraba (CSLH), a nongovernmental organization in a neighborhood
      of extreme poverty in Santiago, Chile. The main components were education,
      maternal and infant health care, support for the mothers, and active
      participation of women from the community served. The program was evaluated
      through indicators of contraceptive use, breastfeeding performance, infant growth
      and health, and a qualitative assessment of women's satisfaction. Controls were
      women of similar characteristics attending the nearby public clinic.
      Acceptability of contraceptive methods was similar but contraceptive options
      differed between clinics. The total number of pregnancies and of respondents lost
      to follow-up was significantly higher for the public clinic than for the CSLH.
      Breastfeeding duration was significantly longer and infant growth and health were
      found to be significantly better at the CSLH than at the public clinic. Women
      valued being treated with respect, receiving education and support, and being
      offered timesaving services and wider contraceptive choices at the CSLH. This
      study demonstrates that such interventions are possible for poor communities,
      providing significant advantages for women and children.

PMID- 16617548
TI  - Maternal mortality among the Kassena-Nankana of northern Ghana.
AB  - This report presents key findings from a maternal mortality study conducted in
      the Kassena-Nankana District of northern Ghana in 1997-98. Sibling history data
      collected in the course of this survey are analyzed together with longitudinal
      data from the Navrongo Demographic Surveillance System (NDSS). A comparison
      between mortality data from these two sources indicates that obtaining reasonably
      accurate estimates of age-specific death rates is possible by using the
      sisterhood method. Direct and indirect estimates from the maternal mortality
      study and the NDSS suggest a decline in the maternal mortality ratio for the
      Kassena-Nankana District from 800 to 600 maternal deaths per 100,000 live births
      over the past 14 years.

PMID- 16617549
TI  - Bangladesh 1996-97: results from the Demographic and Health Survey.

PMID- 16617550
TI  - Senegal 1997: results from the Demographic and Health Survey.

PMID- 16617551
TI  - "History is the present".

PMID- 16617552
TI  - Antibiotic surveillance of Streptococcus pneumoniae in Mississipi.
AB  - OBJECTIVE: A survey of antimicrobial resistance in S. pneumoniae isolates
      collected from representative geographic regions of Mississippi during two
      different respiratory seasons was conducted to determine rates and distribution
      of drug resistance. DESIGN: A total of 318 S. pneumoniae isolates was collected
      from July 1999 to March 2000, and 171 isolates were collected from July 2001 to
      March 2002. The minimum inhibitory concentration for 12 antibiotics was
      determined by the micro dilution method. SETTING: A total of 28 hospitals through
      out the state of Mississippi participated in the submission of S. pneumoniae
      isolates felt to be clinically relevant and reported to the attending physician.
      Specimens were transported to a central laboratory via state health department
      courier. PATIENT POPULATION: Isolates were obtained from hospital inpatients as
      well as outpatients seen in local clinics. MAIN OUTCOME MEASURES: Changes in the
      percentage of isolates resistant to the tested antibiotics and patient
      demographics were collected. RESULTS: Pediatric isolates accounted for 36% and
      28%, respectively, in 2000 and 2002. The relative percentage of total respiratory
      isolates remained for each year. Resistance to penicillin increased in pediatric
      (58% vs. 71%) and adult (40% vs. 52%) as did resistance to ceftriaxone (pediatric
      14% vs. 31%; adult 9% vs. 25%) from 2000 to 2002. The majority of isolates were
      resistant to multiple antibiotics in both years tested. CONCLUSION: The results
      of this study are comparable to those from other national studies of
      antimicrobial resistance in S. pneumoniae demonstrating increasing resistance to
      multiple classes of antibiotics quantitatively and qualitatively.

PMID- 16617553
TI  - Hepatitis A prevalence among injection drug users.
AB  - OBJECTIVE: The purpose of this study was to develop a descriptive model of the
      association between injection drug use and hepatitis A (HAV) in a sample of
      injection drug users (IDUs). DESIGN: From May 1997 to July 1999, 493 subjects
      were administered the NIDA Risk Behavior Assessment (RBA). Participants had blood
      drawn; sera were tested for antibodies to HAV, hepatitis B core (HBcAB), and
      hepatitis C. The principal method of analysis was logistic regression. SETTING:
      The study took place in a community-based field station in Anchorage, Alaska.
      PARTICIPANTS: Eligibility was determined using the following criteria: a) age
      greater than 17 years, b) possession of picture identification, c) positive
      urinalysis for cocaine metabolites, morphine, and/or amphetamines using the
      ONTRAK system (Roche Diagnostics), and d) injection drug use in the last six
      months as confirmed by presentation of track marks. MAIN OUTCOME MEASURE:
      Presence of antibodies to HAV infection. RESULTS: The prevalence of total HAV
      antibody in our sample was 33% (161/493). The final multivariate logistic model,
      using positive HAV serostatus as the outcome, included positive HBcAB serostatus
      (OR = 3.43; 95% CI, 2.22-5.30), less than high school education (vs. high school
      or greater education) (OR = 2.05; 95% CI, 1.33-3.17), age (OR = 1.06 (each year);
      95% CI, 1.03-1.09), number of days injected heroin in the last 30 days (OR = 1.05
      (each day), 95% CI, 1.01-1.08), and race (White vs. all other race/ethnicities)
      (OR = 0.49; 95% CI, 0.32-0.75). CONCLUSIONS: A model including both demographic
      and drug use variables best describes HAV prevalence in this sample. Findings
      suggest that IDUs are targets for interventions focusing on hepatitis
      vaccinations and hygiene practices. Further research is needed to understand the
      association of HAV with hepatitis B infection.

PMID- 16617554
TI  - Interpretation of statistics in clinical laboratory studies.

PMID- 16617555
TI  - Introduction to molecular cystic fibrosis testing.
AB  - Technology improvements are rapidly bringing molecular diagnostics into routine
      laboratories. Recent recommendations for cystic fibrosis carrier testing by the
      American College of Medical Genetics (ACMG) have led to commercial test kit
      development and increased testing volumes. Molecular testing of genetic diseases
      presents a variety of challenges and situations that may be unfamiliar to
      laboratories with limited molecular genetic experience. We will briefly review
      the disease and discuss mutation testing indications, methodologies, quality
      assurance, and reporting issues associated with cystic fibrosis testing.

PMID- 16617556
TI  - Molecular diagnostics of hematological malignancies.

PMID- 16617557
TI  - Regulatory agencies involved with the clinical laboratory.

PMID- 16617558
TI  - Government 101: how an idea becomes law.
AB  - The passing of a law is frequently accompanied by media attention and citizen
      apathy. In today's healthcare delivery situation, we should understand how a bill
      becomes law and what happens to the idea that engenders that process. Laws arise
      from the recommendations of ordinary citizens, but the recommendations follow a
      complicated process developed by the writers of our constitution to prevent
      abuses. Laws begin as ideas, they become bills considered by the legislature,
      they are expanded and enforced by the executive branch, and they are further
      interpreted by the judiciary branch. The laws governing healthcare issues are
      particularly complex, as most arise from the state legislatures.

PMID- 16617559
TI  - Government 103: what happened to the great idea?
AB  - A similar analysis relates to bloodborne pathogens legislation, clinical
      laboratory reimbursement regulations, and Title VII support for health
      professions education. What ultimately happens to a great idea depends on our
      nurture and protection, meanwhile the efforts of others may subjugate its
      purpose. Failure to nurture the idea means it may have a previously undreamed-of
      effect. This commentary on the consequences of political action supports hard
      work, action, and vigilance. The framers intended that the system be energized,
      not paralyzed by multiple checks, balances, controls and remedies. George III
      wasn't big on any of these in the 18th century, so they now exist for the
      protection of us all. That they may seem obtuse is but one more reason for a
      vibrant participatory body politic, players on all sides who care to take the
      time to know the issues and our current boundaries. ASCLS has understood this,
      has taken up the gauntlet and has advocated for our field and its effect on
      patients in need of clinical laboratory tests for longer and with more success
      that any entity in US history. What part can you play in the knowing and the
      doing?

PMID- 16617560
TI  - Chemotherapy treatment options for elderly women with breast cancer.
AB  - Due to improved life expectancy and the increase in incidence of breast cancer in
      old age, ever more older women are developing this disease. Although there is
      only limited evidence-based data from randomized trials on the treatment, older
      patients are still under-represented in clinical studies, and currently there is
      no clear consensus on chemotherapy treatment for older women with breast cancer.
      Adjuvant therapy strategies, in particular, suffer from a lack of uniform
      standards and reflect a generally less aggressive treatment. Recently published
      studies have shown that older women suffering from breast cancer can also profit
      from a treatment based on therapeutic standards and consensus guidelines. In
      spite of developments in adjuvant chemotherapy using increased amounts of
      therapeutic agent to improve survival, many older patients receive instead
      reduced quantities of chemotherapeutic agent. Thus, the questions arise, whether
      undertreatment of older patients with breast cancer can lead to a poorer outcome
      or whether new therapy strategies (e.g., dose-intensive chemotherapy) can be used
      with older patients. A common reason for dose reductions is neutropenia, but
      studies have shown that it is manageable by using granulocyte colony-stimulating
      factors (G-CSFs). In this review, the current status of clinical research in the
      area of adjuvant treatment and the necessity for clinical studies that take into
      account the special therapeutic requirements of older women are discussed.

PMID- 16617561
TI  - Options and limits of surgery after pre-operative chemotherapy in breast cancer.
AB  - The primary administration of chemotherapy leads to a reduction in size of
      tumors, increasing the possibility of breast-conserving surgery in both locally
      advanced, inoperable and primary operable mamma carcinomas. This, however,
      increases the rate of local relapse and the rate of mastectomy over the course of
      the disease, even although the EUSOMA guidelines are not exceeded. Whether the
      pre-surgical administration of chemotherapy with pathological complete remission
      actually increases the disease-free rate and overall survival remains to be
      determined. Further clinical studies are required to establish the reliability of
      sentinel lymph-node biopsy; currently, axillary lymphadenectomy is still the
      standard therapy. The response of the tumor to therapy, in correlation with
      predictive factors and the molecular-genetic profile, could make more
      individualized treatment regimes possible in the future.

PMID- 16617562
TI  - Overexpression of the plasminogen activator inhibitor type-1 in epithelial
      ovarian cancer.
AB  - BACKGROUND: The plasminogen activator-plasmin cascade plays a central role in the
      progression of solid tumors. The type-1 plasminogen activator inhibitor (PAI-1)
      is the major physiological regulator of plasminogen activation. PAI-1 is
      suggested to play a crucial role in tumor cell invasion and metastasis of various
      solid tumors. The aim of this study was to analyze the clinical and prognostic
      roles of PAI-1 in epithelial ovarian cancer (OC). MATERIALS AND METHODS:
      Expression analysis was conducted by immunohistochemistry and ELISA. Tissue
      sections of paraffin-embedded tumor specimens and fresh-frozen tumor samples from
      patients with benign and malignant ovarian tumors (OT), who had undergone
      surgical intervention in the Department of Gynaecology and Obstetrics, Charite,
      Germany, from 02/01 to 06/02, were used. Correlation analysis with conventional
      clinical factors, univariate and multivariate analyses were performed using SPSS
      (SPSS Inc., V.11.0). RESULTS: Sixty-five patients (31 primary OC, 20 recurrent
      OC, 4 low-malignant potential OT, 6 benign OT, 4 normal ovary) were allocated to
      this trial. The median age was 57 years (range, 34-86) and the median follow-up
      was 20 months (range, 0-64). The distributions of (FIGO) tumor stage of all
      primary OC were: I = 16.1%, II = 3.2%, III = 45.2% and IV = 35.5%. PAI-1 was
      significantly overexpressed in the tumor epithelium of OC in comparison to the
      ovarian epithelium of benign OT and normal ovary (p < 0.001). The median PAI-1
      level was 1.92-fold higher in malignant OT than in benign OT. Statistical
      analyses showed no significant correlation between the expression of PAI-1 and
      clinical parameters. The expression of PAI-1 and the PAI-1 level, according to 3
      different cut-off values, showed no prognostic impact in univariate analysis. In
      multivariate analysis, only tumor stage (FIGO) (p = 0.003) and residual tumor (p
      = 0.009) remained independent prognostic factors for post-operative survival.
      CONCLUSION: PAI-1 is significantly overexpressed in OC.

PMID- 16617563
TI  - Videodensitometry in the examination of focal breast lesions after injection of
      an ultrasound contrast agent.
AB  - BACKGROUND: The present investigation aimed at assessing the possibility of
      distinguishing between malignant and benign breast lesions by measuring the
      signal intensity in vessels of the suspect lesions over time after administration
      of the ultrasound contrast agent Levovist. MATERIALS AND METHODS: Levovist was
      administered intravenously to 21 patients with breast cancer and 12 patients with
      a benign breast lesion. In the subsequent ultrasound investigation (Color Power
      Angiography) the resulting increase in brightness over time in the vessels of the
      lesions was measured using the videodensitometry method. From the calculated time
      brightness curves, the time to maximum brightness (T(max)), time to 90% of
      maximum brightness (T(90%)), maximum brightness and other time and brightness
      parameters were determined. The data were analyzed by means of the Mann-Whitney
      Wilcoxon test. Additionally, the sensitivity and specificity were calculated for
      a sequence of cut-off levels for T(90%), T(max) maximum brightness and wash-in
      wash-out parameters. RESULTS: The differences between the benign and the
      malignant lesions for the parameters T(max) and T(90%) were statistically
      significant. The malignant foci showed a significantly more rapid in-flow of the
      contrast agent (p = 0.006) than the benign lesions. The wash-in wash-out time for
      Levovist was significantly shorter for the malignant lesions than for the benign
      lesions (p = 0.02). The time difference in attaining maximum brightness was not
      significant (p = 0.14). The specificity and sensitivity made a more precise
      differentiation between benign and malignant tumors possible. CONCLUSION: The use
      of a contrast agent in Doppler ultrasound enhances the diagnostic reliability in
      distinguishing between malignant and benign lesions, justifying the use of a
      contrast agent with a high specificity (92%) such as Levovist. However, invasive
      pre-operative methods such as punch biopsy are not, thereby, rendered
      unneccessary. It is possible that the combination of Levovist and
      videodensitometry will make it possible to increase the specificity of breast
      cancer diagnosis.

PMID- 16617564
TI  - The orphan nuclear receptors, estrogen receptor-related receptors: their role as
      new biomarkers in gynecological cancer.
AB  - The family of estrogen receptor-related receptors (ERRs) is a subfamily of the
      orphan nuclear receptors, which is closely related to the estrogen receptor (ER)
      family. Research on ERRs has shown that the ERR family share target genes, co
      regulators and promoters with the ER family. ERRs seem to interfere with the
      classic ER-mediated estrogen responsive signaling in various ways. Moreover, ERRs
      have been reported to be prognostic biomarkers in breast, ovarian and colorectal
      cancer. ERRs should be considered as additional factors in the evaluation of
      gynecological tumors. Since ERRs have an important influence on the overall
      estrogenic response, they are of clinical importance in gynecological cancer, but
      also regarding women's general health.

PMID- 16617565
TI  - Postoperative therapy modalities for cervical carcinoma.
AB  - Currently, the standard therapy for cervical carcinoma of FIGO stage IIB
      following adequate radical surgery is simultaneous radiochemotherapy with a
      platinous chemotherapeutic agent. According to the current state of scientific
      knowledge, all patients of FIGO stages IIA-IB with at least one additional risk
      factor (adenocarcinoma, pN1, L1, V1, pT1b2) also benefit from adjuvant
      radiochemotherapy. Various studies have shown that it is possible to successfully
      carry out a platinous radiochemotherapy. However, one disadvantage is that a
      number of patients have to break off therapy because of treatment-related
      toxicities. It has also been proven that a low hemoglobin level during
      radiochemotherapy is a negative prognostic factor for overall survival. The data
      regarding a possible survival advantage following an increase in the hemoglobin
      content in the blood of cancer patients by erythropoietin administration is still
      contradictory. As a result, the administration of new cytostatics, platinous
      combination chemotherapies, sequential instead of simultaneous regimens and
      appropriate supportive therapies have to be taken into account. Several studies
      are currently being conducted into the effectiveness of such new therapies on
      both life expectancy and quality of life (e.g., Cervix-NOGGO-AGO-Uterus 7-study).

PMID- 16617566
TI  - Expression of IL-10 in patients with ovarian carcinoma.
AB  - BACKGROUND: Cytokines are involved in the pathogenesis of different gynecological
      malignancies. Additionally, they stimulate the spread of cancer cells.
      Interleukin 10 (IL-10) was described as a pro-inflammatory factor and seems to be
      implicated in the immune deficiency of patients with cancer. The aim of this
      study was to determine whether the level of IL-10 in the serum and ascites was
      associated with the prognosis of advanced ovarian cancer (OC). MATERIALS AND
      METHODS: In a prospective study from 2001 to 2003, the concentration of IL-10 in
      the serum and ascites of 117 consecutive patients with advanced OC and 30 women
      with benign disease who underwent surgery as a control group (CG), was analyzed
      by the enzyme-linked immunosorbent assay. For statistical analyses, the Chi
      square test by Pearson, Fisher's exact test and the Mann-Whitney test were
      employed. RESULTS: The concentrations of IL-10 were a median of 9.87 pg/ml (range
      7.8 to 500 pg/ml) in the serum and a median of 43.70 pg/ml (range 7.8 to 389.4
      pg/ml) in the ascites of the OC patients. The IL-10 level in the sera of the CG
      was a median of 7.80 pg/ml (range 7.8 to 62.8 pg/ml) and 18.34 pg/ml (range 7.8
      to 88.72 pg/ml) in the peritoneal fluid. A significant association was observed
      between the IL-10 serum levels (p = 0.003) and levels in the peritoneal fluid (p
      = 0.03) in both OC and the CG. IL-10 was significantly more expressed in the
      ascites of patients with OC than in their sera (p = 0.003). The concentration of
      IL-10 correlated significantly with proven conventional prognostic factors such
      as recurrence status (p = 0.005), volume of (ascites, p < 0.001, serum, p =
      0.03), histological grading (p = 0.053) and histological type (ascites p = 0.005/
      serum p = 0.09). There was no significant correlation between the levels of lL-10
      in the ascites and/or serum and FIGO stage, residual tumor mass or age. The cut
      off value of 8.0 pg/ml for IL-10 serum levels had a positive predictive value of
      84% (95% CI: 76-91) and a negative predictive value of 29% (95% CI: 16-41), with
      a specificity and sensibility of 47% (95% CI: 29-65) and 70% (95% CI: 62-78),
      respectively. CONCLUSION: Due to the fact that the levels of IL-10 were
      significantly higher in the ascites and serum of OC patients than in those of the
      CG, IL-10 may play an important immunosuppressive role in the pathogenesis of OC.
      The association between high IL-10 levels in ascites and serum and the
      histological type of the tumor, as well as between the levels in the peritoneal
      cavity and grading, suggest that IL-10 could be a prognostic factor in OC.

PMID- 16617567
TI  - Changes in the circulating plasma levels of VEGF and VEGF-D after adjuvant
      chemotherapy in patients with breast cancer and 1 to 3 positive lymph nodes.
AB  - BACKGROUND: The goal of the present study was to investigate the changes in
      concentration of the important lymph-angiogenesis factors vascular endothelium
      derived growth factor (VEGF) and VEGF-D under adjuvant chemotherapy. MATERIALS
      AND METHODS: The blood plasma of a total of 142 patients with breast carcinoma
      and with 1 to 3 affected lymph nodes was investigated, using the quantitative
      sandwich enzyme immunoassay technique, prior to and following chemotherapy,
      within the framework of a randomized phase III study: the patients received
      either conventional or dose-intensified chemotherapy. RESULTS: In general, there
      was a significant reduction in VEGF levels after chemotherapy only in patients
      with large tumors (T3) (p = 0.043). There was also an almost significant
      reduction in patients with an overexpression of c-erbB-2 (Dako Score +3, p =
      0.052). In contrast, the clearest reduction in VEGF-D occurred in patients with a
      positive hormone receptor status (p = 0.04) or in patients with a low expression
      of c-erbB-2 (Dako Score +1, p = 0.05). A significant effect of chemotherapy on
      VEGF-D was determined only in patients who had a baseline level that was above
      the normal (conventionel treatment p = 0.005; dose-intensified treatment p =
      0.004). CONCLUSION: Both VEGF and VEGF-D levels changed after chemotherapy,
      depending on the patient and tumor characteristics. With respect to changes in
      the plasma levels of VEGF and VEGF-D, there were no significant differences
      between dose-intensified and conventional chemotherapy.

PMID- 16617568
TI  - Actinomycotic inflammatory disease and misdiagnosis of ovarian cancer. A case
      report.
AB  - Actinomycosis in the pelvic region is an uncommon diagnosis. This infection is
      caused by Actinomyces israelii, a gram-positive anerobic saprophyte bacterium
      that is a normal inhabitant of the upper intestinal tract in humans. Pelvic
      actinomycosis is difficult to diagnose pre-operatively and is diagnosed, in most
      cases, accidentally. Actinomycosis can mimic pelvic and abdominal malignancies. A
      case report of a 35-year-old female patient with a fixed pelvic mass is presented
      and the diagnosis and treatment of pelvic actinomycotic inflammatory disease in
      relation to ovarian cancer are discussed. Clinicians should be aware of this rare
      infection to spare women potential morbidity from excessive surgical procedures.

PMID- 16617569
TI  - The impact of interventions on a pre-industrial Austrian Alpine population.
AB  - The purpose of the present study is to gain a better understanding of the role of
      culture in demographic behaviour. The case study uses demographic data to
      illustrate cultural factors intervening in the social organisation of an Austrian
      village in the period 1700-1900. Two sets of potential intervening variables that
      might explain the effects of culture on demographic behaviour were investigated:
      population policies through normative regulations and institutional changes due
      to shifts in government. The paper employs statistical techniques in a structural
      change setting for evaluating the impact of policies and institutional changes on
      the demographic development. There is clear evidence that normative interventions
      concerning the fraction of illegitimate births and the marriage pattern were
      effective.

PMID- 16617570
TI  - Dental wear study in a 14th century skull of the Sao tribe, Cameroon.
AB  - The aim of this work was to study the wear affecting the almost complete
      dentition of a Sao individual fossil from Cameroon prehistory (XIVth century).
      Occlusal surfaces of the fossil fragile pieces were plaster replicated with an
      original technique adapted from usual dental impression methods (silicon
      elastomer polymerising by addition). Axial macro-photographs of both sectional
      dental casts and original pieces made it possible to produce drawings of the
      occlusal areas on transparencies in order to superimpose the lateral hemiarch
      counterparts in their optimal intercuspal position. The study of interarch
      contacts was completed by confronting and observing the occluding position of
      hemiarch replicas. The occlusal analysis revealed that the wear extent was
      equivalent on left and right molars. Hall's occlusal wear index and Van Reenen
      and Reinach's classification of proximal wear allow assessment of the degree of
      wear extent on premolar and molar sections in relation to the side or the arch
      observed. The even bilateral proximal and occlusal wears observed on the
      different kinds of homologous teeth appeared as the main contributor to this well
      balanced interarch occlusion. The mandibular incisor losses and the particular
      type of wear affecting lower canines led to the conclusion of the presence of a
      labret, a great number of which was found in the area. According to Miles' method
      of age assessment based on tooth wear, the pieces studied belonged to an
      individual between 30 and 40 years old.

PMID- 16617571
TI  - Dental contribution to paleo-odontological study of interarch relations in a
      human fossil.
AB  - In paleo-anthropology the fragility of fossil pieces (teeth and supporting bones)
      reduces their possible manipulation when studying the interarch relations. Two
      original impression methods of the jaw pieces are proposed, both adapted from
      those currently practiced in odontology. The plaster replicas of the dental
      occlusal parts are prepared according to the manufacturing procedures used in
      prosthetic dental laboratories. This study led to the following observations: 1)
      the impression techniques used by odontologists are adapted to the moulding of
      fragile samples. 2) The replicas elaborated from these mouldings made easier the
      cast manipulation in confrontation. 3) Macrophotography is a complement to direct
      observation of the pieces and their replicas. 4) For paleoanthropologic purposes,
      such studies can be easily carried out on almost any animal or human fossils.

PMID- 16617572
TI  - Measurement of tooth extraction forces in upper incisors.
AB  - A new method, applied for the first time in this research, was used for
      measurement of tooth extraction forces. The research has been done in a group of
      50 examinees to whom the tooth extraction has been done with lower premolar
      forceps - forceps "13" and in the control group of 54 examinees in whom the tooth
      extraction has been done with upper incisive forceps - forceps "1". The
      measurement instrument registered the extraction forces values in both types of
      forceps. There was no difference in any parameters in these two groups except in
      used pressure. While using the forceps "13", a significantly lower tooth
      extraction force was measured than the force measured while using the forceps "1"
      (p < 0.001). This means that in clinical work we can already apply noticeably
      less force using the lower premolar forceps for the extraction of the upper
      incisors (in the moments of rotation up to 70%). These results are meaningful,
      because they lead to better and improved instrument solutions and working
      techniques.

PMID- 16617573
TI  - Intercondylar distances of the human temporomandibular joints.
AB  - In a sample which included subjects of the Croatian population we made
      measurements of intercondylar distances between the temporomandibular joints in
      radiographs. A total of 101 subjects of both sexes ranging in age from 20 to 80
      years, mostly residents in Zagreb, were evaluated. We measured the intercondylar
      distances from the condyle centers in the postero-anterior cranial radiographs
      which had previously been examined and traced on acetate paper. The measuring
      points were digitized prior to measurements. A special system of coordinates was
      devised for each radiograph. The results of our measurements were assessed by
      ANOVA analysis. The intercondylar distance between the two temporomandibular
      joints was within the range of 110 and 145 mm, with the mean of 126 mm. In men
      the intercondylar distance was within the range of 116 and 145 mm, with the mean
      of 130.2 mm. In women the distance ranged from 110 to 138 mm, with the mean of
      123.5 mm. There was a significant difference between the two sexes. From a review
      of the literature, it is apparent that the results of our measurements do not
      support the results of similar studies assessed by a number of researchers in
      other countries. The intercondylar distance in the Croatian sample was 5.25%
      larger than the maximal values of the same parameters in other populations
      suggesting larger craniofacial skeletons. The development of this radiographic
      assessment method should improve evaluation of subjects seeking treatment.

PMID- 16617574
TI  - Morphometric analysis of the sternum.
AB  - Sternum has a great clinical significance, considering that median sternotomy is
      the most common surgical approach used in cardiac surgery. The aim of this study
      is to standardize the sternum according to size, shape and sex and to obtain
      ranges of the "standard sternum". The study was done on 55 male and 35 female
      sterna of the average age of 65. Complex morphometric analysis of breadth, length
      and thickness of the sterna were performed on sternal segments which were defined
      by costal notches. Morphometric analysis shows that the general sternum structure
      in the females and in the males is equal. The standard dimensions of female and
      male sternum were determined. Standardization according to shape suggests that
      there is one standard sternum shape present in more than 2/3 of analysed samples
      of both sexes.

PMID- 16617575
TI  - Age-related and gender-related differences between human vertebral and iliac
      crest bone--a histomorphometric study on the population of the Mediterranean
      Coast of Croatia.
AB  - In this study, osseous tissue was examined in normal adult population that has
      inhabited areas by the Croatian Adriatic Sea. The most of such studies have shown
      that women are prone to lose bone connectedness, while men are predisposed to be
      a stronger constitution and they start with greater bone mass, though. Bone
      samples from two different anatomic sites were analyzed. The crista iliaca and
      the lumbar vertebra represent functionally different organs too. We wanted to
      consider weather the same age- and gender-related changes affect these two organs
      due to normal aging. Static histomorphometry was used to quantify involution
      changes in the trabecular bone. Results showed that involution process more
      severely affects women than men. Age-related structural changes were more
      prominent in lumbar vertebra than in iliac crest bone. Severe structural changes
      in lumbar vertebra could subsequently lead to a dysfunctional and deformed
      vertebral column. Therefore, iliac crest bone biopsies could hardly explain
      involution process that affects lumbar spine.

PMID- 16617576
TI  - Using magnetic resonance imaging to identify the lumbosacral segment in children.
AB  - Identification of the lumbosacral (L-S) segment on magnetic resonance (MR) images
      is important for appropriate treatment of disease in the lumbosacral (L-S) area.
      In the study, data obtained from plain A-P radiographs of the L-S spine and
      sagittal MR imaging scans (sagittal T1- and T2-weighted sequences) of the L-S
      spine and sacrum with the coccygeal bone, are analyzed. Twenty-six children aged
      10 to 14 years were examined for back pain. On the standard A-P radiographs of
      the L-S spine, a L-S transitional vertebra as classified according to the method
      of Castellvi et al. was found in 17 subjects. The problem arose as to whether
      this was lumbalisation or sacralisation, and how to determine which vertebra was
      L5 wich S1. On the sagittal MR imaging studies the same question applied. A need
      emerged for a simple method which would identify the L-S segment on the sagittal
      MR imaging studies of the L-S spine in children so that in case of a tumor,
      inflammation, spondilolystesis, or protrusion of a disc, the level in the L-S
      spine where the problem is localized can be accurately identified. To this
      objective we selected the method using detection of the S1 vertebra. This
      involved that, in addition to the sagittal MR imaging scans of the L-S spine,
      sagittal images of the sacrum and coccygeal bone be also obtained. on the T2
      weighted sequence, the sacrum can be clearly distinquished from the coccygeal
      bone. By counting from the S5 up, the S1 vertebra can be accurately identified.
      Determination of the S1 vertebra enables detection of the L5 vertebra and, in
      turn, of all other lumbar vertebrae. In patients in whom a T2-weighted MR studies
      were done S1 could be precisely determined and so could the L5 vertebra. In this
      process, whether the patient had a transitional vertebra or whether there was
      lumbarisation or sacralisation was irrelevant.

PMID- 16617577
TI  - Prevalence of scoliosis in school-children from Mostar, Bosnia and Herzegovina.
AB  - In the school-year 2002/2003 a prospective epidemiological study was performed
      with the aim of evaluating the prevalence and distribution of scoliosis in the
      population of schoolchildren from Mostar, Bosnia and Herzegovina. The general
      check-up of primary-school children covered a total of 2,517 children aged 7-14.
      The children in which at least one positive symptom of scoliosis was found were
      directed to undergo orthopedic examination and--if indicated--radiography.
      Incorrect posture was noted in 33.4% of children, and 11.8% of children were sent
      to orthopedic specialist examination. The prevalence of structural scoliosis
      amounted to 3.1%, with the spine curvature threshold being 10 degrees. In eight
      children (0.32%; 1 boy and 7 girls) a curvature of 20 degrees or more was
      diagnosed. The most common type of curvature was the thoracal (39%) and the
      thoraco-lumbar (39%) while 14 children had a double curvature (17.8%). A
      scoliosis was detected due to here performed check-up in 83.5% of children with
      scoliosis. No case of serious spine deformity (45 degree or more) was recorded,
      due to regular general check-ups taking place biannually in this population.

PMID- 16617578
TI  - Growth and secular trend in school-children from Cento, Ferrara, Italy.
AB  - Growth parameters were surveyed in a sample of 296 Italian children, 6-9 years
      old, from Cento (Ferrara, Emilia-Romagna). The comparison with children from the
      same town measured in 1974-75 show changes in some parameters, suggesting an
      ongoing secular trend. To better understand the observed weight increase and the
      sex difference, we also evaluated body composition and motricity. The analysis of
      the present sample is a preliminary part of a longitudinal study dealing with
      modifications of body composition and motor capacity induced by growth. In our
      sample the children are growing according to the Italian reference standard. The
      females present weight, height and Body Mass Index (BMI) values comparable to the
      50th centile, while the males present higher values of weight, skinfold
      thicknesses and BMI. Sex differences in the motor performance were noted. A
      methodological comparison of obesity assessments based on BMI and percentage of
      body fat (%F) shows similar conclusions but somewhat different results.

PMID- 16617579
TI  - Changes of adolescents' defence mechanisms during the first year of high school
      education.
AB  - The goal of this study was to analyse the defence mechanism's changes during
      adolescent's adaptation to the new schooling terms at the first year in high
      school. Sample of 266 students, mean age 15, have been included in the research.
      Kellerman's Life Style Questionnaire (LSQ) was administred for measuring defence
      mechanisms at the beginning and at the end of the school year. Results show that
      regression and reactive formation are changing at most; regression raises (p <
      0.005) while reactive formation decreases (p < 0.000). Boys used repression,
      while girls reactive formation more frequently in both measuring. Displacement
      was 'male" defence in the first measuring; but at repeated measuring this
      difference in sex vanished. The sources of anxiety can be found partly in new
      school environment and in adolescent's effort to "solve the problem" with sexual
      impulses and aggression using different sets of defences.

PMID- 16617580
TI  - Presence of high rates of overweight and obesity among adult Marwaris of Howrah,
      West Bengal, India.
AB  - A cross-sectional study of 220 (110 men and 110 women) adult (> 20 years)
      Marwaris of Howrah, West Bengal, India, was undertaken to investigate the
      frequency of overweight and obesity, using different criteria. Results revealed
      that men had significantly greater mean height, weight, waist circumference (WC),
      waist-hip ratio (WHR), conicity index (CI) and fat free mass (FFM), compared with
      women. Women had significantly higher mean body mass index (BMI), biceps (BSF)
      and triceps (TSF) skinfolds, mid-upper arm (MUAC) and hip (HC) circumferences,
      percent body fat (PBF), fat mass index (FMI), mid-arm fat area (MAFA) and PBF/BMI
      ratio compared with men. The frequency of overweight (BMI > or = 25.0) was
      significantly higher among women (71.8%) compared with men (44.5%). Similarly,
      significantly more women (41.8%) had high WHR than men (22.7%). Significantly
      more women also had high PBF (97.3%) compared with men (90.9%). In conclusion,
      these results demonstrated that the level of overall and central adiposity, as
      well as body fat, was found to be high among Marwaris, as compared with other
      ethnic populations of India. Moreover, there existed significant sexual
      dimorphism in these measures among this ethnic group. This high level of overall
      and central adiposity and body fat could have severe adverse health implications
      in this ethnic group.

PMID- 16617581
TI  - Morphological characteristics, technical and situation efficacy of young female
      volleyball players.
AB  - The aim of the study was to identify differences in morphological variables and
      variables for quality assessment of volleyball techniques in young female
      volleyball players according to age and situation efficacy, and to estimate the
      effect of technique quality on situation efficacy. A set of 13 morphological
      measures and 6 technique elements were used in a sample of 246 female volleyball
      players divided into four age groups: 32 players aged 12-13, 147 players aged 14
      15, 50 players aged 16-17, and 17 players aged 18-19. The quality of performance
      was assessed as a criterion variable. Analysis of variance showed the female
      volleyball players of various age groups to differ significantly according to the
      variables assessing the longitudinal skeleton dimensionality, and body mass and
      volume, as well as in all tests used on volleyball technique evaluation. Analysis
      of variance within particular age groups additionally clarified the process of
      modification in all study variables. Regression correlation analysis indicated
      the set of variables for the 6 evaluated techniques to be a rather good predictor
      of situation efficacy in all age groups, with service technique as the best
      predictor of performance quality in youngest players aged 12-13 and 14-15; spike
      and block techniques in players aged 16-17; and field defense technique in
      players aged 18-19.

PMID- 16617582
TI  - Dietary habits and folate status in women of childbearing age in Croatia.
AB  - Folic acid and folates have an important role in prevention of neural tube defect
      that appears in the first weeks of pregnancy, when women are still not aware of
      their pregnancy, especially when pregnancy is not planned. Since ensuring
      sufficient quantities of folates and folic acid in this period is essential,
      dietary habits of childbearing age women are very important. In line with that
      the intake of folates and folic acid in nutrition of women age group 20-30 years
      is examined, as well as the frequency of consumption of foodstuffs rich in
      vitamins and folic acid supplements. Values of folates in serum are presented,
      dependent on their nutritional habits. Obtained results indicate that in spite of
      inadequate intake of folates and folic acid from foodstuffs, clinical deficit is
      not recorded, which is the result of frequent consumption of dietary supplements.
      In accordance with these dietary habits, differences in the folates status of
      examinees were observed.

PMID- 16617583
TI  - Motor structures in female volleyball players aged 14-17 according to technique
      quality and performance.
AB  - The aim of the study was to identify motor structures in elite female volleyball
      players aged 14-17, and to assess the effect of these motor structures on their
      technical and situation efficiency. For this purpose, a battery of 12 motor tests
      as predictor variables, and a set of six technical elements and evaluation of
      performance quality as criterion variables were applied in a sample of 147 female
      volleyballers aged 14-15 and a sample of 50 female volleyballers aged 16-17.
      Analysis of variance between subgroups within the groups of volleyballers aged 14
      15 and those aged 16-17 showed the results on all motor tests to improve with the
      increase in situation performance, which was especially pronounced in the tests
      assessing explosive strength and agility. The same held true for the results on
      all tests assessing volleyball techniques, spike and block in particular. In both
      samples, factor analysis of motor tests isolated two factors underlain by the
      generation and regulation of strength, and the mechanism of speed regulation.
      Canonical correlation analysis between the motor regulatory mechanisms and
      technical elements revealed determination of the mechanisms of strength and
      technical efficiency in both samples. Regression correlation analysis showed the
      mechanisms of strength regulation and speed to be good predictors of game
      performance in female volleyballers aged 14-15 and 16-17, whereby the mechanism
      of strength regulation had greater effect on the game performance than the
      mechanism of speed regulation. Regression correlation analysis also revealed the
      set of 6 techniques evaluated to be a good predictor of situation efficiency in
      both groups of female volleyballers aged 14-15 and 16-17. The block and spike
      techniques were found to be the best predictors of game performance quality in
      the former, and the techniques of spike and block in the latter. Based on the
      results obtained, a possible model of selection for supreme score achievement in
      female volleyball is described.

PMID- 16617584
TI  - Maternal and fetal outcome in elective versus emergency caesarean section in a
      developing country.
AB  - As the other major European countries, Croatia has also seen a marked increase in
      the rate of caesarean sections. The aim of this study was to determine the most
      common reasons for caesarean section, to compare emergency and elective caesarean
      section in regard to intraoperative and postoperative complications in both
      mother and child, and to assess the decision-to-delivery interval (DDI) in our
      clinic in comparison to current recommendations. Analyzing the results of our
      research we can say that the new-borns in the group with the elective caesarean
      section had considerably better Apgar index score in the first minute (p =
      0.00056) and in the fifth minute (p = 0.054) than the children born in the group
      with emergency caesarean section. Children from the group with elective caesarean
      section had also less frequent asphyxia (p = 0.02315) and considerably less
      frequent resuscitation (p = 0.0143) than the children from the group with
      emergency caesarean sections. Only 39.73% of the emergency caesarean sections
      were performed within the "golden standard" period of 30 minutes. Regarding the
      data from the literature our results are similar with the ones from developed
      countries and 30 minute current standard seem to be not achievable.

PMID- 16617585
TI  - Epidemiology of superficial mycosis (tinea pedis, onychomycosis) in elementary
      school children in Istanbul, Turkey.
AB  - The purpose of this study is to determine the prevalence of tinea pedis and
      onychomycosis in children of elementary school age and to examine the socio
      demographic attributes that may be effective in correlation of both mycoses.
      3,390 female and 3,768 male children between ages 6-14 have been examined in
      seven schools. Skin scrapings and nail samples were taken from 13 students who
      were suspected to have tinea pedis and from 49 students who were suspected to
      have onychomycosis. According to direct microscopy (10-15% KOH+calcofluor white)
      and culturel examination (Sabouraud dextrose agar and dermatophyte test medium)
      11 students were diagnosed as tinea pedis and 24 were diagnosed as onychomycosis.
      Trichophyton rubrum was isolated in 3 students with tinea pedis whose culture was
      positive and five Candida albicans, five Candida glabrata and one Candida
      tropicalis cases were isolated from 11 samples with onychomycosis. Tinea pedis
      prevalence has been found to be 3.3%0. Differences between onychomycosis
      prevalence based on age have been found to be significant (p < 0.001). In
      conclusion, it has been determined that the prevalence of tinea pedis and
      onychomycosis among children is low. Candida spp. was isolated from all of the 14
      samples diagnosed as onychomycosis. Our study shows similar results with previous
      studies done in Turkey and that Trichophyton rubrum continues to be the most
      isolated agent.

PMID- 16617586
TI  - Serum zinc concentrations in the maintenance hemodialysis patients.
AB  - Zinc is necessary for growth and cells' division. Its deficiency may seriously
      affect antioxidant defense system and is usually related to renal failure,
      gastrointestinal diseases and alcoholism. It is very important to know zinc
      status in dialyzed patients and to prevent hypo- or hyperzincemia. Serum samples
      from 89 patients with chronic terminal renal failure on regular hemodialysis were
      withdrawn for the estimation of zinc concentrations immediately before and after
      dialysis. Serum zinc concentrations showed to be highly dependent on
      hemodialysis. In 57 (64%) patients, serum zinc concentrations decreased,
      sometimes from very high to normal values. In remaining 32 (36%) patients serum
      zinc concentrations tended to increase, but remained within normal range. Zinc
      supplementation may be recommended only in the patients with proven zinc
      deficiency, but for all chronic renal failure patients it is questionable.

PMID- 16617587
TI  - Burnout syndrome--assessment of a stressful job among intensive care staff.
AB  - The purpose of the study was to investigate the degree of burnout experienced by
      intensive care staff particularly, in Medical (MICU) and Surgical Intensive Care
      Units (SICU) General Hospital "Sveti Duh", Zagreb. A sample group of 41 emergency
      physicians and nurses from MICU and 30 from SICU was tested. The survey included
      demographic data and Maslach Burnout Inventory (MBI) scoring test identified by
      the three main components associated with burnout: emotional exhaustion (MBI-EE),
      depersonalization (MBI-DEP), and personal accomplishment (MBI-PA) were assessed
      using 22-item questionnaire. The degrees of burnout were stratified into low,
      moderate, and high range. Mean total MBI (X +/- SD) were high in both groups:
      higher for the MICU (65.5 +/- 6.7) than for SICU staff (55.7 +/- 3.8, p < 0.05).
      MICU staff showed moderate degree of MBI-EE (24.9 +/- 11.2), MBI-DEP (6.0 +/-
      5.6), and as well as MBI-PA (34.4 +/- 8.8). The same parameters showed better
      results among SICU staff: low degree of MBI-EE (17.1 +/- 5.2), as well as low
      level of MBI-DEP (5.2 +/- 5.0), and moderate degree of MBI-PA (33.7 +/- 9.8). The
      differences between the groups was statistically significant only for the total
      MBI, and for MBI-EE (p < 0.05). There were no significant differences between
      MICU and SICU staff for MBI-DEP or MBI-PA parameters. Overall job burnout
      represented in a moderate degree. The presence of burnout is a serious
      phenomenon, because it can lead to psychosomatic complaints, work-associated
      withdrawal behaviour, and a lower quality of care at intensive care units. Early
      recognition of burnout phenomenon as a result of prolonged stress and frustration
      among intensive care staff, contributes to better professional behavior,
      organizational structure changes in the work environment and better health care
      quality for critically ill patients.

PMID- 16617588
TI  - Interobserver variability in cytologic subclassification of squamous
      intraepithelial lesions--the Bethesda System vs. World Health Organization
      classification.
AB  - The aim of the study was to compare interobserver variability for The Bethesda
      System (TBS) and World Health Organization (WHO) classification of cervical
      squamous intraepithelial lesions. A total of 1,000 conventional Papanicolaou
      smears (156 positive and 884 negative) were examined "blindly" by three
      cytologists and one cytotechnician. The degree of observer agreement was
      expressed by kappa statistics using a program for the calculation of
      interobserver variation and association "Agree" (Svanholm and Jergensen, 1989).
      Kappa (kappa) was determined for each cytologic diagnosis within a particular
      classification and total for either classification. The association with and
      separation from other diagnoses was determined for each cytologic diagnosis in
      the form of conditional probability (P(j)). In WHO classification, the diagnoses
      of dysplasia media and dysplasia gravis showed poor reproducibility (kappa =
      0.114 and kappa = 0.259, respectively), the diagnosis of dysplasia levis good
      reproducibility (kappa = 0.639), and the diagnosis of carcinoma in situ excellent
      reproducibility (kappa = 0.762). WHO classification yielded pool kappa of 0.741.
      In TBS classification, the diagnosis of LSIL showed good, and HSIL excellent
      reproducibility (kappa = 0.542 and kappa = 0.763, respectively). TBS
      classification yielded pool kappa of 0.699. Dysplasia media (P(j) = 0.121) and
      dysplasia gravis (P(j) = 0.274) were found to be morphologically poorly defined,
      and carcinoma in situ (P(j) = 0.777) and dysplasia levis (P(j) = 0.651) well
      defined diagnoses. LSIL was morphologically moderately defined (P(j) = 0.587) and
      HSIL well defined (P(j) = 0.789) diagnosis. Accordingly, TBS does not
      substantially improve diagnostic reproducibility of the cytologic diagnoses of
      squamous intraepithelial lesions, while providing considerably less information
      to the clinician than the four-grade dysplasia/CIS terminology, thus eliminating
      the opportunity of choosing a different procedure for the diagnosis of dysplasia
      media, which is of utmost importance in the population of young nulliparae.

PMID- 16617589
TI  - Juvenile perpetrators of homicides and attempted homicides--a case control study.
AB  - The aim of this study was to explore the influence of certain aspects of family
      dynamics, as well as some behavior and psychological development disorders on the
      occurrence of homicides and attempted homicides among juveniles in the Split
      Dalmatian County over a period of 10 years (1989-1998). A retrospective case
      control study was performed to compare juvenile murderers and attempted murderers
      with minors who committed other offences, i.e. property crimes. The subjects were
      paired according to demographic and socio-economic background. The data obtained
      from County Court's files included social anamnesis, specialists' observation and
      psychiatric expertise results. There was a significant difference between the
      study group and their controls in the frequency of physical violence and parental
      rejection during childhood. Neuropsychological and neurophysiological
      abnormalities were more frequent in the experimental than in the control group.
      Stealing occurred more often in the control group. No significant differences
      were found for other studied risk factors. There is no unique type of juvenile
      murderer. A juvenile homicide is committed under the influence of various
      developmental characteristics, family milieu, and constitution combined with
      environmental factors and perpetrator's perception of the victim.

PMID- 16617590
TI  - Impact of war on central nervous system tumors incidence--a 15-year retrospective
      study in Istria County, Croatia.
AB  - The aim of study was to analyze epidemiological features of central nervous
      system (CNS) tumors diagnosed in Istria County, Croatia, with a particular
      emphasis on incidence dynamics during the wartime (1991-1995). The data were
      extracted from the medical records of patients with CNS tumors admitted to the
      Department of Neurology of Pula General Hospital in the period from the 1st
      January 1986 to the 31st December 2000, N = 364. For calculation of rates, we
      used data from the 2001 Croatian consensus
      http://www.dzs.hr/Eng/Census/census2001.htm. Data are presented as counts and
      incidence rates (IRs) per 100,000 persons-years in the case of annual rates.
      Annual incidence rates are shown as "raw" incidence rates and smoothed 5-year
      rolling average rates. The examined patient-related variables were: sex, age,
      occupation, premorbidity and comorbidity, with a particular emphasis on
      psychosomatic disorders and negative habits. The analyzed tumor-related variables
      included clinical manifestation, localization, and applied diagnostic and
      therapeutic methods. Primary tumors were separated from the metastatic, and the
      latter were analysed with respect to their site of origin. The lowest incidence
      of CNS tumors (10 patients) was reported in 1990, and the highest (42 patients)
      in 1993. The incidence dynamics of CNS tumors showed a rapidly progressive
      increase over the 1991-1995 period, followed by the return to average values. The
      access to a better and more readily available diagnostics may only partially
      explain this phenomenon. Therefore, we analyzed other factors that may have
      contributed towards the rapid increase in the number of CNS tumors, such as its
      coincidence with the war or psychotrauma. The results confirm the observational
      clinical hypothesis of an extreme increase in the number of CNS tumors during the
      period under consideration.

PMID- 16617591
TI  - Incidence of pituitary tumors in the human population of Croatia.
AB  - Pituitary tumors are rare tumors (less then 10%) of the central nervous system
      (CNS), which malignicity depends on their localization, meanwhile, their
      biological nature is benign. The diameter they have is mostly less then 10 mm
      (microadenomas), but sometimes could be 10 mm (macroadenomas) to 5 cm and more
      and then are usually nonfunctional (about 20% of all pituitary tumors). Clinical
      presence depends on their localisation and hormonal activity. In the Center for
      Clinical Neuroendocrinology and Pituitary Diseases, in the last working 10 years,
      there were treated and examined 504 patients from Croatia, all with pituitary
      tumors: 182 patients with prolactinomas, 137 with acromegaly, 70 with Morbus
      Cushing (Mb. Cushing), and 115 patients with nonfunctional pituitary tumors. The
      patient's classification is based on regional (Mediterranean and continental
      region, 20 counties) and the state level. In our analysis we haven't found
      difference in incidence of tumors between Mediterranean and continental region.

PMID- 16617592
TI  - Analysis of the qualitative dermatoglyphics of the digito-palmar complex in
      patients with primary open angle glaucoma.
AB  - The primary open-angle glaucomas are a group of diseases that have in common
      characteristic morphological changes at the optic nerve head and retinal nerve
      fiber layer, progressive retinal ganglion cells death and characteristic visual
      field loss. The risk for primary open angle glaucoma rises continuously with the
      level of the intraocular pressure. The disease advances slowly and there are no
      symptoms. Primary open angle glaucoma is caused by abnormal aqueous humour
      outflow in the trabecular meshwork in the open angle. Etiopathogenesis of primary
      open angle glaucoma is unclear. The increased risk of glaucoma in relatives has
      long been recognized. Frequency for manifestation of the disease is 10-30% in
      family members. The discovery of the specific gene loci responsible for the
      manifestation of glaucoma has helped us to understand its mechanism of origin and
      definitely confirmed the hereditary nature of this disease. Digito-palmar
      dermatoglyphs were already used to determine hereditary base of many diseases and
      it was the reason for investigation of their qualitative patterns in patients
      with glaucoma (22 males and 23 females), their immediate relatives (19 males and
      23 females) in comparison to a group of phenotypically healthy population (52
      males and 56 females). The results pointed a connection with the dermatoglyphic
      traits of the digito-palmar complex between patients with glaucoma and their
      immediate relatives. There is a possible discrimination of patients and their
      immediate relatives from phenotypically healthy population, too.

PMID- 16617593
TI  - Leber's hereditary optic neuroretinopathy (LHON) associated with mitochondrial
      DNA point mutation G11778A in two Croatian families.
AB  - Leber's hereditary optic neuroretinopathy (LHON) is manifested as a bilateral
      acute or subacute loss of central vision due to optic atrophy. It is linked to
      point mutations of mitochondrial DNA, which is inherited maternally. The most
      common mitochondrial DNA point mutations associated with LHON are G3460A, G11778A
      and T14484C. These mutations are linked with the defects of subunits of the
      complex I (NADH-dehydrogenase-ubiquinone reductase) in mitochondria. The G11778A
      mitochondrial DNA point mutation is manifested by a severe visual impairment. In
      this paper two Croatian families with the LHON G11778A mutation are presented.
      Three LHON patients from two families were younger males which had the visual
      acuity of 0.1 or below, the ophthalmoscopy revealed telangiectatic
      microangiopathy and papilloedema, while Goldmann kinetic perimetry showed a
      central scotoma. The mothers and female relatives were LHON mutants without
      symptoms, whereas their sons suffered from a severe visual impairment. Molecular
      diagnosis helps to explain the cause of LHON disease.

PMID- 16617594
TI  - Marked improvement in survival among adult Croatian AIDS patients after the
      introduction of highly active antiretroviral treatment.
AB  - We compared the survival of patients following the first AIDS event in Croatia
      from the period 1986-1996 to the period 1997-2000. A total of 72 (81.8%) out of
      88 patients from 1986-1996 and 18 (32.1%) out of 56 from 1997-2000 died. Survival
      following the first AIDS-defining illness markedly improved in the period 1997
      2000 compared to the period 1986-1996 (adjusted Hazard Ratio (HR) for patients
      surviving more than 6 months: 0.11, 95% confidence interval (95% CI) = 0.04
      0.29). A CD4+ cell count of < 100 x 10(6)/L was an independent risk factor for
      patients surviving up to 2 years (adjusted HR = 1.96, 95% CI = 1.1-3.43, p =
      0.02). Patients with tuberculosis or fungal infections had a longer survival when
      compared to other diagnosis (adjusted HR = 0.53, 95% CI = 0.32-0.90, p = 0.01).
      However, despite dramatic survival benefit of combination antiretroviral therapy,
      mortality at six months following the first AIDS event was similar in the two
      study periods and the one-year probability of death was still substantial (27.2%)
      in the period 1997-2000.

PMID- 16617595
TI  - Atopy patch test with Dermatophagoides pteronyssinus (Dp 1) in atopic dermatitis
      patients.
AB  - The aim of this study was to evaluate the role of Dermatophagoides pteronyssinus
      (Dp) in atopic dermatitis patients, using atopy patch test (APT) with Dp (extract
      1). Twenty patients (males (m) = 9, females (f) = 11, mean age = 46.0 years,
      range = 19-78 years) with atopic dermatitis were involved in this study. The
      control group consisted of seventeen healthy subjects (m = 7, f = 10, mean age =
      48.3, range = 24-64 years), with no personal or family history and no signs of
      atopy. Total IgE, specific IgE and a skin prick test were done for all subjects
      involved in this study. The atopy patch tests were performed with Dp (extract 1)
      in: 3,000, 10,000, 20,000 and 30,000 biological units per ml (BU/ml)
      concentrations using glycerol as medium. The total IgE was significantly higher
      in atopic dermatitis (AD) patients than in a control group with (p < 0.05). After
      the tests six of twenty patients (30%) had positive APT results in the last two
      concentrations (20,000 and 30,000 BU/ml). However, all the results were positive
      after 48 h (and 72 hours), while no positive results were recorded in the control
      subjects. According to our study, APT with Dp 1 in 20,000 BU/ml and reading time
      48 h and 72 hours is to be recommended. The results suggest that APT may detect
      the trigger factor (Dp) in AD patients.

PMID- 16617596
TI  - Combined action of virus injection and local tumor irradiation on tumor growth in
      mice.
AB  - The dynamics of SCCVII transplantable tumor growth in C3H/H mice was determined
      after local tumor irradiation and/or virus (NDV LaSota) i.p. injection. The virus
      applied alone significantly suppressed tumor growth, particularly until the 19th
      day after tumor transplantation. Local irradiation with 30 Gy resulted in tumor
      disappearance followed with its regrowth about 15 days later. However, if the
      virus was injected after the irradiation, there was no tumor growth until the end
      of the 31 day observation period. It should be noted that virus application prior
      to local irradiation did not have any additional influence on tumor growth. Thus,
      the pronounced efficacy of virus applied after tumor irradiation deserves
      attention. It is possible that the virus injected after irradiation induced a
      chain of cytokine production joining the action of tumor destruction induced by
      irradiation. This should be further studied in clarifying the approaches to
      combined tumor therapy with possible cell-free vaccine production.

PMID- 16617597
TI  - Venomous snakebites in southern Croatia.
AB  - This retrospective study is based on the analysis of 542 snakebite envenomation
      cases in southern Croatia, which were treated in the University Hospital Split
      over the period of 21 years. The aim of this study was to determine the incidence
      of venomous snakebite in southern Croatia, epidemiological and clinical features
      of snakebite and treatment in the region. The mean annual snakebite incidence in
      southern Croatia was 5.2 per 100,000 inhabitants. The nose- horned viper (Vipera
      ammodytes) was responsible for most bites, only a small proportion being
      inflicted by the adder (Vipera berus). People of all ages were affected (1 - 82
      year old), but the bites were more frequent in individuals older than 50 (46% of
      the cases) and in children and adolescents 19 year old and younger (27% of the
      cases). Most snakebite accidents happened in warm spring and summer months, the
      highest number occurring in May (22%). A majority of the victims were rural
      people engaged in agricultural activities. Bites on the upper limbs were more
      frequent (57%) than bites on the lower limbs (42%). With regard to envenomation
      severity, there were 15.1% minor, 40.5% mild, 26% moderate and 18% severe cases.
      Two victims died (0.4%). The antivenom produced by the Institute of Immunology in
      Zagreb was given to virtually all patients, and complications following its
      administration were rare. The antivenom was used more often than it was suggested
      by the symptoms present.

PMID- 16617598
TI  - Isonymic analysis of population structure in Gredos, Spain.
AB  - For the period 1875-1975 an isonymic analysis was made based on 41,696 marriages
      celebrated in three valleys (Tormes, Alberche and Tietar) from Gredos (Spain).
      Total inbreeding (Ft) was lower in the Tietar valley (0.0103- 0.0136), followed
      by the Tormes (0.0125-0.0255) and the Alberche (0.0153-0.0200). In the latter,
      random inbreeding (Fr) surpassed non random (Fn). Correlation coefficients were
      obtained to confirm an association of inbreeding from isonymy with valley and
      village endogamy rates, locality census, altitude, and alpha inbreeding. Fn
      correlated positively with average valley endogamy and village endogamy and with
      altitude, but inversely with census size. Contrarily, Fr related significantly to
      village endogamy. The non-random component from isonymy related positively to
      inbreeding from dispensations. Except for village endogamy, both variables show
      the same relationships to variables, such as altitude, which reflect limitations
      to mobility; or valley endogamy indicating the disposability of potential mates
      which in turn depends on the census size.

PMID- 16617599
TI  - Hypnosis and modern frontal-lobe concepts--a sketch for a review and an
      invitation to one particularly promising field.
AB  - The present paper intends to briefly review the most important concepts of the
      modern neuropsychology of the frontal lobes, and to relate these findings to the
      phenomenology usually encountered in hypnosis research and practice. The frontal
      lobes have been studied very intensively during the last several years and some
      of the results, including the syndromes described in frontal-lobe lesions and
      psychiatric patients, demonstrate striking similarity with hypnotic phenomena.
      Based on these similarities, an alternative neuropsychophysiological definition
      of hypnosis/suggestion is proposed, viewing hypnosis/suggestion as the process of
      external manipulation with frontal-lobe functions with consequent effects upon
      the entire brain potential of the subject.

PMID- 16617600
TI  - Does chronological age reduce working ability?
AB  - Definitions of so-called older age often are based on a chronological age of 65
      years and over, although by some authors aging is the process that starts after
      the 30th year of life. At the beginning occur changes in the organ functions,
      followed by anatomical changes as well. Some organs age faster, some slower. For
      example, kidneys decrease for one third, lungs do not change, liver shrinks a
      little, prostate increases twice. In some cross-sectional studies, muscle mass in
      men aged 65 is on average 12 kg less than in the so-called middle age, and in
      women it is approximately 5 kg less. In the heart the amount of connective tissue
      increases, lipofuscin is deposited in cardiac muscle, the strength of which is
      decreasing. In the respiratory tract the number of pathways cilia decreases,
      along with the alveolar surface, muscles involved in breathing change, lung
      elasticity is also diminished. But, in regard with the previous body capacity,
      "physiological aging" can be divided into three types of elderly: the "older"
      elderly have the highest functional capacity of 2-3 MET (MET--metabolic unit,
      i.e. the oxygen consumption of 3.5 ml/kg body mass in a minute), the "younger"
      elderly are the persons of older age having maximal functional capacity of 5-7
      MET, while the "sport" elderly have the functional capacity of 9-10 MET,
      disregarding chronological age. The brain weight diminishes for approximately 7%
      compared to younger age. In temporal gyrus and area striata even 20-40% of cells
      are being lost, vacuolar and neuroaxonal degeneration occurs, lipofuscin is being
      accumulated. The brain blood flow, which is in normal conditions 50-60 ml/min/100
      g of tissue, with the increase of biological age decreases to about 40 ml/min/100
      g of tissue. However, this usually is not the consequence of biological age but
      of disease. A chronological age of 65 for the beginning of "elder hood" is a
      sociopolitical construct developed by social security systems and government
      organizations to decide an arbitrary age at which benefits should be paid. Thus,
      it neither a border nor do changes designating old age occurs exactly with that
      "age border". The changes in the organism during the so-called aging are
      individual. So, the functional capacity of an organism, both physical and
      intellectual, must be evaluated individually, having in mind biological age.

PMID- 16617601
TI  - Clinical presentation of a patient with congenital polycythemia.
AB  - The authors describe a 19 year old male with an isolated but absolute
      erythrocytosis with iron deficiency without evidence for polycythemia vera as
      well as another causes of erythrocytosis. The polycythemia was due to a recently
      described von Hippel-Lindau (VHL) mutation. By stopping iron therapy there was no
      more requirements for phlebotomy in this patient.

PMID- 16617602
TI  - Local recurrence of primary non-ampullary adenocarcinoma of duodenum after
      surgical treatment--a case report and a literature review.
AB  - Worldwide there is no general attitude on optimal surgical procedure in treatment
      of primary non-ampullary adenocarcinoma of duodenum, especially for early stage
      of duodenal cancer. Some authors prefer local excision and segmental resection
      while others rather perform duodenopancreatic resection, even in the case of
      early stage of duodenal cancer with aim to avoid tumor recurrence. In this paper
      we present a rare clinical course of a 60-year-old male patient with an
      endoscopically and pathohistologically proven early stage duodenal cancer that
      was treated by wide local excision. Three years after operation, control
      endoscopy showed "flat" polyp in the duodenum and radical duodenopancreatic
      resection was performed. Pathohistological examination of resected specimen
      showed cancer that had spread throughout the duodenal wall with metastases in the
      regional lymph nodes. According to our findings and literature review we gave
      some direction concerning the optimal diagnostic and surgical procedure for this
      rare tumor.

PMID- 16617603
TI  - Esthetic reconstruction of teeth in patient with dentinogenesis imperfecta--a
      case report.
AB  - Dentinogenesis imperfecta (DI) is the result of a dominant genetic defect and
      affects both the deciduous and permanent dentitions. It is characterized by
      opalescent teeth composed of irregularly formed and undemineralized dentin which
      obliterates pulp chamber and root canal. DI can appear as a separate disorder or
      with osteogenesis imperfecta (OI). The teeth with DI show a grayish-blue to brown
      hue with dislodged enamel, dysplastic dentine with irregular dentinal tubules and
      interglobular dentine, short roots and pulpal obliteration, which all may lead to
      rapid and extensive attrition which require adequate crown reconstruction. The
      aim of this study was to show a reconstruction of frontal teeth in upper jaw with
      direct composite veneers in young adult patient with DI.

PMID- 16617604
TI  - A rare case of multiple aneurysms in a young patient.
AB  - Multiple aneurysms are clinically common in population aged over sixty and are
      caused mainly by atherosclerosis. When occurring in young population other
      etiologies such as trauma, infections, Bechet's disease, Marfan syndrome,
      neurofibromatosis or inflammatory disease are responsible for the development of
      arterial aneurysms. A rare case of multiple aneurysms in a 40-year-old man,
      affecting the infrarenal part of abdominal aorta, both iliac arteries, common
      femoral arteries, left femoral superficial and popliteal arteries on, both legs,
      is reported. The underlying pathology was progressive atherosclerosis, favored by
      familial hyperlipidemia and excessive cigarette smoking.

PMID- 16617605
TI  - Intravascular lymphoma and thyroid gland.
AB  - Intravascular lymphoma (IVL) is a rare disease characterized by the proliferation
      of neoplastic cells in the small blood vessels that frequently goes undiagnosed
      until the time of autopsy. The neoplastic cells are usually of B-cell origin. The
      clinical course was examined to determine factors that would facilitate
      antemortem diagnosis. IVL is observed with clinical, histopathological and
      immunohystochemical methods. This is a unique case because the thyroid gland is a
      rare place for IVL. Accent is given on immunohystochemical methods and tissue
      biopsy in the differential diagnosis of IVL when nervous system and thyroid gland
      dysfunction occur This report indicates that micro-ecosystem of multinodular
      goitrous might influence the expression of chemokines and/or adhesion moleculs on
      endothelial and lymphoma cells, leading to heavy infiltration of thyroid gland.
      Concurrently, that may guide the physician to tissue biopsy facilitating
      antemortem diagnosis and institution of appropriate therapy.

PMID- 16617606
TI  - Giant perianal angiomyofibroblastoma--a case report.
AB  - A 45-year old female had a long history of slow growing perianal tumor at the
      right side of her anus. Encapsulated tumour was found intraoperatively and
      completely excised using the Harmonic Scalpel. Tumour was well-circumscribed and
      relatively firm; measuring 12x6x4 cm. Histologically it was composed of oval to
      spindle cells with minimal nuclear atypia, set in mucous matrix with numerous
      thin-walled blood vessels. Immunohistochemically, expression of smooth-muscle
      actin and desmin, as well as estrogen and progesterone receptor were found in the
      tumour cells. The diagnosis of angiomyofibroblastoma was established. This rare
      benign tumour typically involves vulvovaginal, pelvic and perinal region. It is
      important to separate this neoplasm from locally invasive aggressive angiomyxoma
      and low grade fibromyxoid sarcoma, which can arise in the the same localisation.
      The patient was discharged on the third postoperative day and no recurrence was
      noted in 18 months follow-up.

PMID- 16617607
TI  - Neurofibromatosis type 1 in pregnancy.
AB  - The report presents two cases of neurofibromatosis type 1 one previously known
      and one detected during pregnancy. It describes how the disease was detected and
      diagnosed, and what was the outcome of pregnancies. This is the first case of
      prenatal neurofibromatosis type 1 diagnosed in our clinic.

PMID- 16617608
TI  - Laparoscopic abdominal cysts fenestration using harmonic scalpel.
AB  - The use of ultrasonically activated scalpel for tissue cutting and coagulation is
      a potential replacement for electrosurgery, which can be related to different
      complications. Its working principle is to transform the electric power into the
      mechanical longitudinal movement of the working part of the instrument, by a
      piezoelectric transducer situated in the hand piece. Between October 2000 and
      June 2004, six patients with abdominal cysts were treated by laparoscopy, using
      the harmonic scalpel. The average age was 40.8 (ranging from 15-60) years.
      Laparoscopic abdominal cyst fenestration was performed in five patients, and
      laparoscopic cholecystectomy and abdominal cyst fenestration were done in one
      patient during the same operation. The average duration of the operation was 40
      (ranging from 25-70) minutes and hospital stay was 2.8 (ranging from 1-5) days.
      Laparoscopic abdominal cyst fenestration using the harmonic scalpel is a safe and
      successful operation, with good results including all the advantages of the
      minimally invasive surgery.

PMID- 16617609
TI  - Framework for parsing, visualizing and scoring tissue microarray images.
AB  - Increasingly automated techniques for arraying, immunostaining, and imaging
      tissue sections led us to design software for convenient management, display, and
      scoring. Demand for molecular marker data derived in situ from tissue has driven
      histology informatics automation to the point where one can envision the
      computer, rather than the microscope, as the primary viewing platform for
      histopathological scoring and diagnoses. Tissue microarrays (TMAs), with hundreds
      or even thousands of patients' tissue sections on each slide, were the first step
      in this wave of automation. Via TMAs, increasingly rapid identification of the
      molecular patterns of cancer that define distinct clinical outcome groups among
      patients has become possible. TMAs have moved the bottleneck of acquiring
      molecular pattern information away from sampling and processing the tissues to
      the tasks of scoring and results analyses. The need to read large numbers of new
      slides, primarily for research purposes, is driving continuing advances in
      commercially available automated microscopy instruments that already do or soon
      will automatically image hundreds of slides per day. We reviewed strategies for
      acquiring, collating, and storing histological images with the goal of
      streamlining subsequent data analyses. As a result of this work, we report an
      implementation of software for automated preprocessing, organization, storage,
      and display of high resolution composite TMA images.

PMID- 16617610
TI  - LEAD: a methodology for learning efficient approaches to medical diagnosis.
AB  - Determining the most efficient use of diagnostic tests is one of the complex
      issues facing medical practitioners. With the soaring cost of healthcare,
      particularly in the US, there is a critical need for cutting costs of diagnostic
      tests, while achieving a higher level of diagnostic accuracy. This paper develops
      a learning based methodology that, based on patient information, recommends
      test(s) that optimize a suitable measure of diagnostic performance. A
      comprehensive performance measure is developed that accounts for the costs of
      testing, morbidity, and mortality associated with the tests, and time taken to
      reach diagnosis. The performance measure also accounts for the diagnostic ability
      of the tests. The methodology combines tools from the fields of data mining
      (rough set theory, in particular), utility theory, Markov decision processes
      (MDP), and reinforcement learning (RL). The rough set theory is used in
      extracting diagnostic information in the form of rules from the medical
      databases. Utility theory is used in bringing various nonhomogenous performance
      measures into one cost based measure. An MDP model together with an RL algorithm
      facilitates obtaining efficient testing strategies. The methodology is
      implemented on a sample problem of diagnosing solitary pulmonary nodule (SPN).
      The results obtained are compared with those from four alternative testing
      strategies. Our methodology holds significant promise to improve the process of
      medical diagnosis.

PMID- 16617611
TI  - Enhanced real-time ECG coder for packetized telecardiology applications.
AB  - A new real-time compression method for electrocardiogram (ECG) signals has been
      developed based on the wavelet transform approach. The method is specifically
      adaptable for packetized telecardiology applications. The signal is segmented
      into beats and a beat template is subtracted from them, producing a residual
      signal. Beat templates and residual signals are coded with a wavelet expansion.
      Compression is achieved by selecting a subset of wavelet coefficients. The number
      of selected coefficients depends on a threshold which has different definitions
      depending on the operational mode of the coder. Compression performance has been
      tested using a subset of ECG records from MIT-BIH Arrhythmia database. This
      method has been designed for real-time packetized telecardiology scenarios both
      in wired and wireless environments.

PMID- 16617612
TI  - A novel evolutionary drug scheduling model in cancer chemotherapy.
AB  - In this paper, we introduce a modified optimal control model of drug scheduling
      in cancer chemotherapy and a new adaptive elitist-population-based genetic
      algorithm (AEGA) to solve it. Working closely with an oncologist, we first modify
      the existing model, because its equation for the cumulative drug toxicity is
      inconsistent with medical knowledge and clinical experience. To explore multiple
      efficient drug scheduling policies, we propose a novel variable representation--a
      cycle-wise representation, and modify the elitist genetic search operators in the
      AEGA. The simulation results obtained by the modified model match well with the
      clinical treatment experiences, and can provide multiple efficient solutions for
      oncologists to consider. Moreover, it has been shown that the evolutionary drug
      scheduling approach is simple, and capable of solving complex cancer chemotherapy
      problems by adapting multimodal versions of evolutionary algorithms.

PMID- 16617613
TI  - Using generalized additive models for construction of nonlinear classifiers in
      computer-aided diagnosis systems.
AB  - Several investigators have pointed out the possibility of using computer-aided
      diagnosis (CAD) schemes, as second readers, to help radiologists in the
      interpretation of images. One of the most important aspects to be considered when
      the diagnostic imaging systems are analyzed is the evaluation of their diagnostic
      performance. To perform this task, receiver operating characteristic curves are
      the method of choice. An important step in nearly all CAD systems is the
      reduction of false positives, as well as the classification of lesions, using
      different algorithms, such as neural networks or feature analysis, and several
      statistical methods. A statistical model more often employed is linear
      discriminant analysis (LDA). However, LDA implies several limitations in the type
      of variables that it can analyze. In this work, we have developed a novel
      approach, based on generalized additive models (GAMs), as an alternative to LDA,
      which can deal with a broad variety of variables, improving the results produced
      by using the LDA model. As an application, we have used GAM techniques for
      reducing the number of false detections in a computerized method to detect
      clustered microcalcifications, and we have compared this with the results
      obtained when LDA was applied. Employing LDA, the system achieved a sensitivity
      of 80.52% at a false-positive rate of 1.90 false detections per image. With the
      GAM, the sensitivity increased to 83.12% and 1.46 false positives per image.

PMID- 16617614
TI  - Information mining over heterogeneous and high-dimensional time-series data in
      clinical trials databases.
AB  - An effective analysis of clinical trials data involves analyzing different types
      of data such as heterogeneous and high dimensional time series data. The current
      time series analysis methods generally assume that the series at hand have
      sufficient length to apply statistical techniques to them. Other ideal case
      assumptions are that data are collected in equal length intervals, and while
      comparing time series, the lengths are usually expected to be equal to each
      other. However, these assumptions are not valid for many real data sets,
      especially for the clinical trials data sets. An addition, the data sources are
      different from each other, the data are heterogeneous, and the sensitivity of the
      experiments varies by the source. Approaches for mining time series data need to
      be revisited, keeping the wide range of requirements in mind. In this paper, we
      propose a novel approach for information mining that involves two major steps:
      applying a data mining algorithm over homogeneous subsets of data, and
      identifying common or distinct patterns over the information gathered in the
      first step. Our approach is implemented specifically for heterogeneous and high
      dimensional time series clinical trials data. Using this framework, we propose a
      new way of utilizing frequent itemset mining, as well as clustering and
      declustering techniques with novel distance metrics for measuring similarity
      between time series data. By clustering the data, we find groups of analytes
      (substances in blood) that are most strongly correlated. Most of these
      relationships already known are verified by the clinical panels, and, in
      addition, we identify novel groups that need further biomedical analysis. A
      slight modification to our algorithm results an effective declustering of high
      dimensional time series data, which is then used for "feature selection." Using
      industry-sponsored clinical trials data sets, we are able to identify a small set
      of analytes that effectively models the state of normal health.

PMID- 16617615
TI  - Information extraction from sound for medical telemonitoring.
AB  - Today, the growth of the aging population in Europe needs an increasing number of
      health care professionals and facilities for aged persons. Medical telemonitoring
      at home (and, more generally, telemedicine) improves the patient's comfort and
      reduces hospitalization costs. Using sound surveillance as an alternative
      solution to video telemonitoring, this paper deals with the detection and
      classification of alarming sounds in a noisy environment. The proposed sound
      analysis system can detect distress or everyday sounds everywhere in the
      monitored apartment, and is connected to classical medical telemonitoring sensors
      through a data fusion process. The sound analysis system is divided in two
      stages: sound detection and classification. The first analysis stage (sound
      detection) must extract significant sounds from a continuous signal flow. A new
      detection algorithm based on discrete wavelet transform is proposed in this
      paper, which leads to accurate results when applied to nonstationary signals
      (such as impulsive sounds). The algorithm presented in this paper was evaluated
      in a noisy environment and is favorably compared to the state of the art
      algorithms in the field. The second stage of the system is sound classification,
      which uses a statistical approach to identify unknown sounds. A statistical study
      was done to find out the most discriminant acoustical parameters in the input of
      the classification module. New wavelet based parameters, better adapted to noise,
      are proposed in this paper. The telemonitoring system validation is presented
      through various real and simulated test sets. The global sound based system leads
      to a 3% missed alarm rate and could be fused with other medical sensors to
      improve performance.

PMID- 16617616
TI  - Modeling of workflow-engaged networks on radiology transfers across a metro
      network.
AB  - Radiology metro networks bear the challenging proposition of interconnecting
      several hospitals in a region to provide a comprehensive diagnostic imaging
      service. Consequences of a poorly designed and implemented metro network could
      cause delays or no access at all when health care providers try to retrieve
      medical cases across the network. This could translate into limited diagnostic
      services to patients, resulting in negative impacts to the patients' medical
      treatment. A workflow-engaged network (WEN) is a new network paradigm. A WEN
      appreciates radiology workflows and priorities in using the network. A WEN
      greatly improves the network performance by guaranteeing that critical image
      transfers experience minimal delay. It adjusts network settings to ensure the
      application's requirements are met. This means that high-priority image transfers
      will have guaranteed and known delay times, whereas lower-priority traffic will
      have increased delays. This paper introduces a modeling to understand the
      benefits that WEN brings to a radiology metro network. The modeling uses actual
      data patterns and flows found in a hospital metro region. The workflows
      considered are based on the Integrating the Healthcare Enterprise profiles. This
      modeling has been applied to metropolitan workflows of a health region. The
      modeling helps identify the kind of metro network that supports data patterns and
      flows in a metro area. The results of the modeling show that a 155-Mb/s
      metropolitan area network (MAN) with WEN operates virtually equal to a normal 622
      Mb/s MAN without WEN, with potential cost savings for leased line services
      measured in the millions of dollars per year.

PMID- 16617617
TI  - Virtual reality in posturography.
AB  - Balance dysfunctions are common, especially among elderly people. Present methods
      for the diagnosis and evaluation of severity of dysfuntion have limited value. We
      present a system that makes it easy to implement different visual and mechanical
      perturbations for clinical investigations of balance and visual-vestibular
      interaction. The system combines virtual reality visual stimulation with force
      platform posturography on a moving platform. We evaluate our contruction's
      utility in a classification task between 33 healthy controls and 77 patients with
      Meniere's disease, using a series of tests with different visual and mechanical
      stimuli. Responses of patients and controls differ significantly in parameters
      computed from stabilograms. We also show that the series of tests achieves a
      classification accuracy slightly over 80% between controls and patients.

PMID- 16617618
TI  - Blind source separation for ambulatory sleep recording.
AB  - This paper deals with the conception of a new system for sleep staging in
      ambulatory conditions. Sleep recording is performed by means of five electrodes:
      two temporal, two frontal and a reference. This configuration enables to avoid
      the chin area to enhance the quality of the muscular signal and the hair region
      for patient convenience. The electroencephalopgram (EEG), eletromyogram (EMG),
      and electrooculogram (EOG) signals are separated using the Independent Component
      Analysis approach. The system is compared to a standard sleep analysis system
      using polysomnographic recordings of 14 patients. The overall concordance of
      67.2% is achieved between the two systems. Based on the validation results and
      the computational efficiency we recommend the clinical use of the proposed system
      in a commercial sleep analysis platform.

PMID- 16617619
TI  - Automatic image hanging protocol for chest radiographs in PACS.
AB  - Chest radiography is one of the most widely used techniques in diagnostic
      imaging. It comprises at least one-third of all diagnostic radiographic
      procedures in hospitals. However, in the picture archive and communication
      system, images are often stored with the projection and orientation unknown or
      mislabeled, which causes inefficiency for radiologists' interpretation. To
      address this problem, an automatic hanging protocol for chest radiographs is
      presented. The method targets the most effective region in a chest radiograph,
      and extracts a set of size-, rotation-, and translation-invariant features from
      it. Then, a well-trained classifier is used to recognize the projection. The
      orientation of the radiograph is later identified by locating the neck, heart,
      and abdomen positions in the radiographs. Initial experiments are performed on
      the radiographs collected from daily routine chest exams in hospitals and show
      promising results. Using the presented protocol, 98.2% of all cases could be hung
      correctly on projection view (without protocol, 62%), and 96.1% had correct
      orientation (without protocol, 75%). A workflow study on the protocol also
      demonstrates a significant improvement in efficiency for image display.

PMID- 16617620
TI  - GiPSi:a framework for open source/open architecture software development for
      organ-level surgical simulation.
AB  - This paper presents the architectural details of an evolving open source/open
      architecture software framework for developing organ-level surgical simulations.
      Our goal is to facilitate shared development of reusable models, to accommodate
      heterogeneous models of computation, and to provide a framework for interfacing
      multiple heterogeneous models. The framework provides an application programming
      interface for interfacing dynamic models defined over spatial domains. It is
      specifically designed to be independent of the specifics of the modeling methods
      used, and therefore facilitates seamless integration of heterogeneous models and
      processes. Furthermore, each model has separate geometries for visualization,
      simulation, and interfacing, allowing the model developer to choose the most
      natural geometric representation for each case. Input/output interfaces for
      visualization and haptics for real-time interactive applications have also been
      provided.

PMID- 16617621
TI  - A planning system based on Markov decision processes to guide people with
      dementia through activities of daily living.
AB  - Older adults with dementia often cannot remember how to complete activities of
      daily living and require a caregiver to aid them through the steps involved. The
      use of a computerized guidance system could potentially reduce the reliance on a
      caregiver. This paper examines the design and preliminary evaluation of a
      planning system that uses Markov decision processes (MDPs) to determine when and
      how to provide prompts to a user with dementia for guidance through the activity
      of handwashing. Results from the study suggest that MDPs can be applied
      effectively to this type of guidance problem. Considerations for the development
      of future guidance systems are presented.

PMID- 16617622
TI  - Association rule discovery with the train and test approach for heart disease
      prediction.
AB  - Association rules represent a promising technique to improve heart disease
      prediction. Unfortunately, when association rules are applied on a medical data
      set, they produce an extremely large number of rules. Most of such rules are
      medically irrelevant and the time required to find them can be impractical. A
      more important issue is that, in general, association rules are mined on the
      entire data set without validation on an independent sample. To solve these
      limitations, we introduce an algorithm that uses search constraints to reduce the
      number of rules, searches for association rules on a training set, and finally
      validates them on an independent test set. The medical significance of discovered
      rules is evaluated with support, confidence, and lift. Association rules are
      applied on a real data set containing medical records of patients with heart
      disease. In medical terms, association rules relate heart perfusion measurements
      and risk factors to the degree of disease in four specific arteries. Search
      constraints and test set validation significantly reduce the number of
      association rules and produce a set of rules with high predictive accuracy. We
      exhibit important rules with high confidence, high lift, or both, that remain
      valid on the test set on several runs. These rules represent valuable medical
      knowledge.

PMID- 16617623
TI  - High-performance medical image registration using new optimization techniques.
AB  - Optimization of a similarity metric is an essential component in intensity-based
      medical image registration. The increasing availability of parallel computers
      makes parallelizing some registration tasks an attractive option to increase
      speed. In this paper, two new deterministic, derivative-free, and intrinsically
      parallel optimization methods are adapted for image registration. DIviding
      RECTangles (DIRECT) is a global technique for linearly bounded problems, and
      multidirectional search (MDS) is a recent local method. The performance of
      DIRECT, MDS, and hybrid methods using a parallel implementation of Powell's
      method for local refinement, are compared. Experimental results demonstrate that
      DIRECT and MDS are robust, accurate, and substantially reduce computation time in
      parallel implementations.

PMID- 16617624
TI  - Effects of JPEG2000 data compression on an automated system for detecting
      clustered microcalcifications in digital mammograms.
AB  - The functionalities of the JPEG2000 standard have led to its incorporation into
      digital imaging and communications in medicine (DICOM), which makes this
      compression method available for medical systems. In this study, we evaluated the
      compression of mammographic images with JPEG2000 (16 : 1, 20 : 1, 40 : 1, 60.4 :
      1, 80: 1, and 106 : 1) for applications with a computer-aided detection (CAD)
      system for clusters of microcalcifications. Jackknife free-response receiver
      operating characteristic (JAFROC) analysis indicated that differences in the
      detection of clusters of microcalcifications were not statistically significant
      for uncompressed versus 16: 1 (T = -0.7780; p = 0.4370), 20 : 1 (T = 1.0361; p =
      0.3007), and 40 : 1 (T = 1.6966; p = 0.0904); and statistically significant for
      uncompressed versus 60.4 : 1 (T = 5.8883; p < 0.008), 80 : 1 (T = 7.8414; p <
      0.008), and 106 : 1 (T = 17.5034; p = < 0.008). Although there is a small
      difference in peak signal-to-noise ratio (PSNR) between compression ratios, the
      true-positive (TP) and false-positive (FP) rates, and the free-response receiver
      operating characteristic (FROC), figure of merit values considerably decreased
      from a 60 : 1 compression ratio. The performance of the CAD system is
      significantly reduced when using images compressed at ratios greater than 40 : 1
      with JPEG2000 compared to uncompressed images. Mammographic images compressed up
      to 20 : 1 provide a percentage of correct detections by our CAD system similar to
      uncompressed images, regardless of the characteristics of the cluster. Further
      investigation is required to determine how JPEG2000 affects the detectability of
      clusters of microcalcifications as a function of their characteristics.

PMID- 16617625
TI  - Automatic 3-D grayscale volume matching and shape analysis.
AB  - Recently, shape matching in three dimensions (3-D) has been gaining importance in
      a wide variety of fields such as computer graphics, computer vision, medicine,
      and biology, with applications such as object recognition, medical diagnosis, and
      quantitative morphological analysis of biological operations. Automatic shape
      matching techniques developed in the field of computer graphics handle object
      surfaces, but ignore intensities of inner voxels. In biology and medical imaging,
      voxel intensities obtained by computed tomography (CT), magnetic resonance
      imagery (MRI), and confocal microscopes are important to determine point
      correspondences. Nevertheless, most biomedical volume matching techniques require
      human interactions, and automatic methods assume matched objects to have very
      similar shapes so as to avoid combinatorial explosions of point. This article is
      aimed at decreasing the gap between the two fields. The proposed method
      automatically finds dense point correspondences between two grayscale volumes;
      i.e., finds a correspondent in the second volume for every voxel in the first
      volume, based on the voxel intensities. Mutiresolutional pyramids are introduced
      to reduce computational load and handle highly plastic objects. We calculate the
      average shape of a set of similar objects and give a measure of plasticity to
      compare them. Matching results can also be used to generate intermediate volumes
      for morphing. We use various data to validate the effectiveness of our method: we
      calculate the average shape and plasticity of a set of fly brain cells, and we
      also match a human skull and an orangutan skull.

PMID- 16617626
TI  - The emergency department triage of community-acquired pneumonia project data and
      documentation systems: a model for multicenter clinical trials.
AB  - Multicenter clinical trials are complex undertakings that require significant
      resources to ensure efficient, high quality research. This paper describes the
      goals, design, and implementation of a multicenter clinical trial database
      management system to support this aim. A large number of study sites or patients,
      and the goal of automatically generating large portions of data management
      infrastructure from common metadata, motivated the development of the system.
      This paper also describes extensions for a generalized project documentation
      system, and discusses plans for further extensions and improvements based on
      observed strengths, limitations, and anticipated technological change.

PMID- 16617627
TI  - Fast maximum intensity projections of large medical data sets by exploiting
      hierarchical memory architectures.
AB  - Maximum intensity projections (MIPs) are an important visualization technique for
      angiographic data sets. Efficient data inspection requires frame rates of at
      least five frames per second at preserved image quality. Despite the advances in
      computer technology, this task remains a challenge. On the one hand, the sizes of
      computed tomography and magnetic resonance images are increasing rapidly. On the
      other hand, rendering algorithms do not automatically benefit from the advances
      in processor technology, especially for large data sets. This is due to the
      faster evolving processing power and the slower evolving memory access speed,
      which is bridged by hierarchical cache memory architectures. In this paper, we
      investigate memory access optimization methods and use them for generating MIPs
      on general-purpose central processing units (CPUs) and graphics processing units
      (GPUs), respectively. These methods can work on any level of the memory
      hierarchy, and we show that properly combined methods can optimize memory access
      on multiple levels of the hierarchy at the same time. We present performance
      measurements to compare different algorithm variants and illustrate the influence
      of the respective techniques. On current hardware, the efficient handling of the
      memory hierarchy for CPUs improves the rendering performance by a factor of 3 to
      4. On GPUs, we observed that the effect is even larger, especially for large data
      sets. The methods can easily be adjusted to different hardware specifics,
      although their impact can vary considerably. They can also be used for other
      rendering techniques than MIPs, and their use for more general image processing
      task could be investigated in the future.

PMID- 16617628
TI  - Computer-aided continuous drug infusion: setup and test of a mobile closed-loop
      system for the continuous automated infusion of insulin.
AB  - For a diabetes mellitus patient, tight control of glucose level is essential.
      Results are reported of an investigation of the suitability of existing wearable
      continuous insulin infusors controlled and adjusted by a control algorithm using
      continuous glucose measurements as input to perform the functionality of an
      artificial pancreas. Special attention was given to the development of a
      continuous glucose monitor and to evaluate which quality of input data is
      necessary for the control algorithm. In clinical trials, it was found that for
      patients in a controlled environment an autonomously regulating control algorithm
      leads to an improved adjustment of patient glucose values and less overall
      insulin infusion as compared with the best fixed preprogrammed insulin infusion
      profiles of standard pump therapy. For the limited number of cases studied here,
      functionality of the control algorithm could tolerate some delay between the
      actual glucose values in the patient interstitial fluid and the algorithm input
      of up to 30 min. A quasicontinuous glucose measurement delivering actual glucose
      values every 5-10 min seems to be suited to control an artificial pancreas.

PMID- 16617629
TI  - A Java-based enterprise system architecture for implementing a continuously
      supported and entirely Web-based exercise solution.
AB  - Since machine-based exercise still uses local facilities, it is affected by time
      and place. We designed a web-based system architecture based on the Java 2
      Enterprise Edition that can accomplish continuously supported machine-based
      exercise. In this system, exercise programs and machines are loosely coupled and
      dynamically integrated on the site of exercise via the Internet. We then extended
      the conventional health promotion model, which contains three types of players
      (users, exercise trainers, and manufacturers), by adding a new player: exercise
      program creators. Moreover, we developed a self-describing strategy to
      accommodate a variety of exercise programs and provide ease of use to users on
      the web. We illustrate our novel design with examples taken from our feasibility
      study on a web-based cycle ergometer exercise system. A biosignal-based workload
      control approach was introduced to ensure that users performed appropriate
      exercise alone.

PMID- 16617630
TI  - Long-term telemonitoring of mobility trends of elderly people using SMS
      messaging.
AB  - A telemonitoring system, based on short message service (SMS), has been developed
      to remotely monitor the long-term mobility levels of elderly people in their
      natural environment. Mobility is measured by an accelerometer-based portable
      unit, worn by each monitored subject. Mobility level summaries are transmitted
      hourly, as an SMS message, directly from the portable unit to a remote server for
      long-term analysis. Each subject's mobility levels are monitored using custom
      designed mobility alert software, and the appropriate medical personnel are
      alerted by SMS if the subject's mobility levels decrease.

PMID- 16617631
TI  - Watershed-presegmented snake for boundary detection and tracking of left
      ventricle in echocardiographic images.
AB  - In this paper, an automated method of boundary detection of the left ventricle
      (LV) is proposed. The method uses a watershed transform and morphological
      operation to locate the region containing the LV, then performs snake deformation
      with a multiscale directional edge map for the detection of the endocardial
      boundary of the LV.

PMID- 16617632
TI  - Ray casting with "on-the-fly" region growing: 3-D navigation into cardiac MSCT
      volume.
AB  - This paper describes an extended ray casting scheme for three-dimensional (3-D)
      navigation into the heart cavities for preoperative planning using multislice X
      ray computed tomography data. The key benefit is that artifacts due to contrast
      inhomogeneities can be eliminated during volume traversal, thus improving the
      visual perception of the endocardial wall.

PMID- 16617633
TI  - Muscle relaxants--pancuronium and vecuronium.

PMID- 16617634
TI  - "Just put it in!" Consent for epidural analgesia in labour.

PMID- 16617635
TI  - B-type natriuretic peptide concentrations and myocardial dysfunction in critical
      illness.
AB  - B-type natriuretic peptide (BNP) is the first biomarker of proven value in
      screening for left ventricular dysfunction. The availability of point-of-care
      testing has escalated clinical interest and the resultant research is defining a
      role for BNP in the investigation and treatment of critically ill patients. This
      review was undertaken with the aim of collecting and assimilating current
      evidence regarding the use of BNP assay in the evaluation of myocardial
      dysfunction in critically ill humans. The information is presented in a format
      based upon organ system and disease category. BNP assay has been studied in a
      spectrum of clinical conditions ranging from acute dyspnoea to subarachnoid
      haemorrhage. Its role in diagnosis, assessment of disease severity, risk
      stratification and prognostic evaluation of cardiac dysfunction appears
      promising, but requires further elaboration. The heterogeneity of the critically
      ill population appears to warrant a range of cut-off values. Research addressing
      progressive changes in BNP concentration is hindered by infrequent assay and
      appears unlikely to reflect the critically ill patient's rapidly changing
      haemodynamics. Multi-marker strategies may prove valuable in prognostication and
      evaluation of therapy in a greater variety of illnesses. Scant data exist
      regarding the use of BNP assay to alter therapy or outcome. It appears that BNP
      assay offers complementary information to conventional approaches for the
      evaluation of cardiac dysfunction. Continued research should augment the validity
      of BNP assay in the evaluation of myocardial function in patients with life
      threatening illness.

PMID- 16617636
TI  - Methods to assess performance of models estimating risk of death in intensive
      care patients: a review.
AB  - Models that estimate the probability of death of intensive care unit patients can
      be used to stratify patients according to the severity of their condition and to
      control for casemix and severity of illness. These models have been used for risk
      adjustment in quality monitoring, administration, management and research and as
      an aid to clinical decision making. Models such as the Mortality Prediction Model
      family, SAPS II, APACHE II, APACHE III and the organ system failure models
      provide estimates of the probability of in-hospital death of ICU patients. This
      review examines methods to assess the performance of these models. The key
      attributes of a model are discrimination (the accuracy of the ranking in order of
      probability of death) and calibration (the extent to which the model's prediction
      of probability of death reflects the true risk of death). These attributes should
      be assessed in existing models that predict the probability of patient mortality,
      and in any subsequent model that is developed for the purposes of estimating
      these probabilities. The literature contains a range of approaches for assessment
      which are reviewed and a survey of the methodologies used in studies of intensive
      care mortality models is presented. The systematic approach used by Standards for
      Reporting Diagnostic Accuracy provides a framework to incorporate these
      theoretical considerations of model assessment and recommendations are made for
      evaluation and presentation of the performance of models that estimate the
      probability of death of intensive care patients.

PMID- 16617637
TI  - Quality of life at three years after cardiac surgery: relationship with
      preoperative status and quality of recovery.
AB  - A reduction in symptoms, increased longevity, and improved quality of life (QoL),
      are goals of cardiac surgery. We measured QoL in 108 adult cardiac surgical
      patients at about three years after cardiac surgery, and assessed the predictive
      ability of a 40-item quality of recovery (QoR-40) score. Our follow-up rate was
      86% (n = 93). When compared with preoperative status, QoL was improved at three
      years after surgery (P < 0.0005). The dimensions of QoL that were most affected
      were physical functioning, role limitations due to physical problems, vitality,
      social functioning, and role limitations due to emotional problems (all P <
      0.005). There was a mild correlation between the day 3 QoR-40 and the three year
      SF-36, r = 0.23 (P = 0.029). There was a strong correlation between the three
      year QoR-40 and the three year SF-36, r = 0.73 (P < 0.0005). The QoR-40 and SF-36
      done at three years after cardiac surgery demonstrated good internal consistency,
      QoR-40 alpha = 0.86 (P < 0.0005), SF-36 alpha = 0.91 (P < 0.0005). A poor quality
      recovery in the days after surgery can predict a poor QoL at three years after
      surgery. The QoR-40 is a valid and reliable measure of quality of recovery after
      surgery and anaesthesia. The QoR-40 is a useful, patient-oriented method of
      assessing recovery from anaesthesia and surgery.

PMID- 16617638
TI  - Estimate of the number of patients eligible for treatment with drotrecogin alfa
      (activated) based on differing international indications: post-hoc analysis of an
      inception cohort study in Australia and New Zealand.
AB  - We aimed to estimate the potential number of patients eligible for treatment with
      drotrecogin alfa (activated) when applying different international criteria. The
      study was a post-hoc analysis of inception cohort study of 691 patients with
      severe sepsis during 5878 consecutive intensive care unit admission episodes in
      23 closed multi-disciplinary ICUs of 21 hospitals (16 tertiary and 5 university
      affiliated) in Australia and New Zealand. Outcomes assessed were presence of
      contraindications to treatment with drotrecogin alfa (activated), an admission
      APACHE II score of 25 or greater and dysfunction of two or more organs. During
      5878 consecutive intensive care admission episodes, 691 patients had severe
      sepsis, 553 (80.0%, 95% CI 77.0-83.0%) had no relative or absolute
      contraindication, 64 (9.3%, 7.1-11.4%) had a relative contraindication and 74
      (10.7%, 8.4-13.0%) had an absolute contraindication. Two hundred and six patients
      (3.5%, 3.0-4.0%) had an APACHE II score of 25 or greater, 452 (7.7%, 7.0-8.4%)
      had dysfunction of two or more organs, 469 (8.0%, 7.3-8.7%) had either
      dysfunction of two or more organs or an APACHE II score of 25 or greater
      Relatively few patients had an absolute contraindication to treatment with
      drotrecogin alfa (activated). Selection based on the APACHE II score results in
      fewer eligible patients than selection based on multiple organ dysfunction.
      Depending on the selection criteria used, for every hundred admissions to
      intensive care, between 3.5 and 8.0 of patients may be eligible for treatment
      with drotrecogin alfa (activated).

PMID- 16617639
TI  - Failure of a quality improvement process to increase nutrition delivery to
      intensive care patients.
AB  - The importance of nutrition support in intensive care has been recognised, but
      many factors may limit successful provision of patients' requirements. We
      conducted a twelve-month prospective audit, with intervention after six months,
      to determine whether longer-stay (> 3 days) patients in our intensive care unit
      were receiving their nutritional requirements and to identify and improve factors
      limiting nutrition provision. Data was collected for 379 consecutive patients
      admitted to intensive care longer than three days. Total energy provided to each
      patient was recorded daily and compared with the predicted requirement. In the
      first six months, patients commenced nutrition 2.2 +/- 1.3 days after intensive
      care admission and were receiving 100% of predicted energy requirement by 4.8 +/-
      3.3 days. Patients received nutrition on 82.3% of total patient-days, daily
      average 71.7% (43.2) of their energy requirement. Nutrition was interrupted on
      30% of total patient-days. After six months, a Clinical Practice Improvement
      model was used to analyse reasons for inadequate feeding and introduce changes in
      practice. Main reasons for interruption included preparation for extubation and
      upper gastrointestinal intolerance. After intervention, interruptions due to
      these reasons were significantly reduced, however, no significant improvement was
      observed overall, either in the time to reach nutritional goals, or in the amount
      of energy received. Successful changes in practice, targeting only one or two
      main issues, can be overwhelmed by other factors. To effect significant
      improvement, a wider approach may be required.

PMID- 16617640
TI  - Predictive performance of a model of anaesthetic uptake with desflurane.
AB  - We have previously shown that a model of anaesthetic uptake and distribution,
      developed for use as a teaching tool, is able to predict end-tidal isoflurane and
      sevoflurane concentrations at least as well as commonly used propofol models
      predict blood levels of propofol. Models with good predictive performance may be
      useful as part of real-time prediction systems. The aim of this study was to
      assess the performance of this model with desflurane. Twenty adult patients
      undergoing routine anaesthesia were studied. The total fresh gas flow and
      vaporizor settings were collected at 10-second intervals from the anaesthetic
      machine. These data were used as inputs to the model, which had been initialized
      for patient weight and desflurane. Output of the model is a predicted end-tidal
      value at each point in time. These values were compared with measured end-tidal
      desflurane using a standard statistical technique of Varvel and colleagues. Data
      was analysed from 19 patients. Median performance error was 78% (95% CI 8-147),
      median absolute performance error 77% (6-149), divergence 10.6%/h (-80-101) and
      wobble 8.9% (-6-24). The predictive performance of this model with desflurane was
      poor, with considerable variability between patients. The reasons for the
      difference between desflurane and our previous results with isoflurane and
      sevoflurane are not obvious, but may provide important clues to the necessary
      components for such models. The data collected in this study may assist in the
      development and evaluation of improved models.

PMID- 16617641
TI  - Anatomical study of the brachial plexus using surface ultrasound.
AB  - The aim of this study was to define the anatomy relevant to brachial plexus
      regional anaesthesia and to identify the extent of variation between individuals.
      Surface ultrasound examination of the brachial plexus was performed on twenty
      volunteers. In the axilla there was considerable individual variation in the
      location of the median, radial and ulnar nerves in relation to the axillary
      artery. There was often more than one venous structure in this region, which was
      easily compressed by surface palpation. In the supraclavicular region, neural
      elements were located inferiorly to the subclavian artery in two volunteers. In
      one volunteer, a vein was identified between nerve trunks in the interscalene
      region. These findings indicate that the anatomical variation is considerable,
      even within the relatively small sample studied. For this reason, use of surface
      ultrasound may lead to increased success of brachial plexus regional anaesthesia
      and a decreased risk of intravascular injection.

PMID- 16617642
TI  - Dynamic airflow limitation after topical anaesthesia of the upper airway.
AB  - This prospective before-and-after observational study investigated the effect of
      upper airway anaesthesia on dynamic airflow. Six consenting ASA 1 adults, all
      authors of this study, underwent a series of spirometric measurements before and
      after topical anaesthesia of the upper airway using lignocaine. Peak inspiratory
      flow rate, forced inspiratory flow between 25% and 75% of the maximum inhaled
      volume, forced expiratory volume at 1 second, and forced vital capacity in the
      supine and sitting positions were measured. The measured inspiratory parameters
      were significantly reduced after lignocaine topical anaesthesia of the upper
      airway. Expiratory flow parameters were not affected. We conclude that topical
      anaesthesia of the upper airway leads to dynamic inspiratory airflow limitation.

PMID- 16617643
TI  - Radiation exposure during anaesthetic practice.
AB  - With anaesthesia being administered more often outside of theatre in areas such
      as radiology suites, the occupational risk to anaesthetists from ionizing
      radiation may have increased. To determine radiation exposure from X-ray sources
      during normal anaesthetic practice, passive personal radiation monitoring devices
      were used to record the occupational exposure to radiation of 29 anaesthetists
      over a one calendar month period. Occupational whole body effective dose was
      calculated and extrapolated to give an estimated annual radiation exposure. Seven
      of the 29 anaesthetists recorded a dose that was higher than the minimum
      detectable limit. Extrapolating to estimate yearly doses, no anaesthetist would
      have approached the annual occupational dose limits for ionizing radiation. The
      maximum extrapolated annual whole body effective dose was 2.14 mSv, the
      Australian Recommendation and National Standard for occupational exposure being
      less than 20 mSv per year. The anaesthetist with the highest exposure would have
      exceeded the yearly recommended exposure limit for pregnant women (1 mSv). Even
      if they had worked all sessions in a radiation exposed environment, this person
      would not have exceeded the yearly annual occupational dose limits for ionizing
      radiation for non-pregnant staff provided they had worn a standard protective
      lead gown. The collar dose for this person was 7.08 mSv which may represent a
      significant risk to the thyroid if a protective lead collar was not worn.
      Although anaesthetists' radiation exposure is within acceptable limits, caution
      should be taken in rostering pregnant staff to anaesthetize where radiation
      exposure occurs, and all anaesthetists should routinely wear thyroid collars in
      such areas.

PMID- 16617644
TI  - The neurotoxic effects of intrathecal midazolam and neostigmine in rabbits.
AB  - In parallel with improvements in understanding pain neurophysiology, many
      chemicals have recently been investigated for spinal anaesthesia and analgesia.
      However, studies discussing the effects of these drugs on neural tissue indicate
      that knowledge about some aspects of neurotoxicity is limited. Forty-nine New
      Zealand albino rabbits, weighing 2.2 +/- 0.2 kg, were randomly assigned to seven
      groups of seven animals each. Single dose groups received intrathecally through
      the atlantooccipital membrane 0.9% saline 1.5 ml; midazolam 100 microg/kg (low
      dose midazolam group) or 500 microg/kg (high dose midazolam group); neostigmine
      10 microg/kg (low dose neostigmine group) or 50 microg/kg (high dose neostigmine
      group). Two groups had seven days of repeated dosing with either midazolam 100
      microg/kg/day (repeat midazolam group) or 10 microg/kg/day neostigmine (repeat
      neostigmine group). The animals were sacrificed on day 8, and two spinal cord
      sections from the fourth cervical level and fourth lumbar level were removed and
      prepared for histopathological study. Transmission electron microscopic
      evaluations were performed on transverse spinal cord sections by a
      neuropathologist blinded to the group allocation. Twenty myelinated axons and
      neurones in the cervical and lumbar sections were investigated for the
      histopathological study. This study indicates that midazolam and neostigmine have
      different neurotoxic effects that depend on the dose and the repetition of dosing
      when these drugs are administered intrathecally.

PMID- 16617645
TI  - Effect of scalp block on postoperative pain relief in craniotomy patients.
AB  - The efficacy of scalp nerve block using 0.5% bupivacaine with adrenaline for
      postoperative pain relief in craniotomy patients was evaluated in 40 ASA I or II
      adult patients undergoing supratentorial craniotomy. A standard general
      anaesthesia technique was followed. Patients were randomly divided into two
      groups. Group B received 0.5% bupivacaine with 1:400,000 adrenaline and group S
      received normal saline with 1:400,000 adrenaline, both after skin closure.
      Postoperative pain was assessed at 30 seconds and 1, 2, 4, 6, 8 and 12 hours
      using a numerical rating scale. Diclofenac IM was administered as rescue
      analgesia if patients reported a numerical rating scale of 40 or more. Tramadol
      IV was administered as second rescue analgesia. Sixty per cent of patients in
      group S experienced moderate to severe pain (numerical rating scale of 40 or
      more) at some time during the first 12 postoperative hours in comparison to 25%
      patients in group B. Median pain scores were significantly lower in group B for
      up to 6 hours. Significantly more patients were pain free up to four hours in
      group B. Median duration for the requirement of first dose of diclofenac was
      longer in group B compared to group S (360 min vs 30 min, P < 0.01). The number
      of doses of diclofenac (5 vs 19) was significantly lower in group B compared to
      group S (P < 0.01). Tramadol was required by six patients in group S only. Scalp
      nerve block using 0.5% bupivacaine with 1:400,000 adrenaline decreases the
      incidence and severity of postoperative pain in patients undergoing
      supratentorial craniotomy.

PMID- 16617646
TI  - Incidents during out-of-hospital patient transportation.
AB  - Out-of-hospital patient transportation (retrieval) of critically ill patients
      occurs within highly complex environments. Adverse events are not uncommon.
      Incident monitoring provides a means to better understand such events. The aim of
      this study was to characterize incidents occurring during retrieval to provide a
      basis for developing corrective strategies. Four organizations contributed 125
      reports, documenting 272 incidents; 91% of forms documented incidents as
      preventable. Incidents related to equipment (37%), patient care (26%), transport
      operations (11%), interpersonal communication (9%), planning or preparation (9%),
      retrieval staff (7%) and tasking (2%). Incidents occurred during patient
      transport to the receiving facility (26%), at patient origin (26%), during
      patient loading (20%), at the retrieval service base (18%) and receiving facility
      (9%). Contributing factors were system-based for 54% and human-based for 42%.
      Haste (7.5%), equipment malfunctioning (7.2%) or missing (5.5%), failure to check
      (5.8%) and pressure to proceed (5.2%) were the most frequent contributing
      factors. Harm was documented in 59% of incidents with one death. Minimizing
      factors were good crew skills/teamwork (42%), checking equipment (17%) and
      patient (8%), patient monitors (15%), good luck (14%) and good interpersonal
      communication (4%). Incident monitoring provides sufficient insight into
      retrieval incidents to be a useful quality improvement tool for retrieval
      services. Information gathered suggested improvements in retrieval equipment
      design and use of alternative power sources, the use of pro formae for equipment
      checking, patient assessment, preparation for transportation and information
      transfer Lessons from incidents in other areas applicable to retrieval should be
      linked for analysis with retrieval incidents.

PMID- 16617647
TI  - A comparison of the oropharyngeal leak pressure between the reusable Classic
      laryngeal mask airway and the single-use Soft Seal laryngeal mask airway.
AB  - We tested the oropharyngeal leak pressure with the reusable laryngeal mask airway
      and the single-use Soft Seal laryngeal mask airway. These two types of laryngeal
      mask airway (LMA) have a similar design but the reusable LMA cuff is made from
      silicone whereas the Soft Seal LMA cuff is polyvinylchloride. Thirty-five healthy
      subjects were anaesthetized and paralyzed and the two types of Soft Seal LMA were
      compared in a blinded randomized cross-over trial. The oropharyngeal leak
      pressure was significantly higher with the Soft Seal than the reuable (21 +/- 7.6
      and 16 +/- 6.7 cm H2O respectively, P = 0.002). However, in four subjects the
      oropharyngeal leak pressure was higher with the reusable by > 4 cm H2O. We
      concluded that the reusable LMA may provide a better seal in some individuals but
      that, on average, the Soft Seal provides a higher oropharyngeal leak pressure
      than the reusable LMA.

PMID- 16617648
TI  - Ultrasound guided deep cervical plexus block.
AB  - We describe a new technique for achieving a deep cervical plexus block using a
      portable vascular access ultrasound scanner (Site-Rite II, Bard Access Systems,
      Pittsburgh, PA).

PMID- 16617649
TI  - An introductory guide to survey research in anaesthesia.
AB  - Surveys allow convenient and inexpensive research. Surveys include mail-out
      questionnaires, email questionnaires, telephone interviews, and personal
      interviews. Despite a widespread perception that surveys are easy to conduct,
      good surveys need rigorous design, implementation and analysis. This requires
      substantial planning, time and effort. The most important step in designing a
      survey is to clearly define the question(s) the survey aims to answer The target
      population, measured variables and types of associations being investigated
      should be specific and unambiguous. Investigators should concentrate on what they
      'need to know' rather than what would be 'nice to know'. During development
      surveys should be piloted to identify problems. The main goal when implementing a
      survey is to maximize the response rate to avoid misleading results. Evidence
      based strategies, including brief personalized surveys with stamped return
      envelopes, can be used to maximize the response rate. A poorly conducted survey
      can lead to misleading or invalid conclusions and may undermine participation in
      subsequent surveys by the target population.

PMID- 16617650
TI  - Issues of consent for regional analgesia in labour: a survey of obstetric
      anaesthetists.
AB  - Anaesthetists are legally obliged to obtain consent and inform patients of
      material risks prior to administering regional analgesia in labour. We surveyed
      consultant members of the Australian and New Zealand College of Anaesthetists
      with a special interest in obstetric anaesthesia, in order to identify and
      compare which risks of regional analgesia they report discussing with women prior
      to and during labour. We also asked about obstetric anaesthetists' beliefs about
      informed consent, the type of consent obtained and its documentation. Of 542
      questionnaires distributed, 291 responses (54%) were suitable for analysis. The
      five most commonly discussed risks were post dural puncture headache, block
      failure, permanent neurological injury, temporary leg weakness and hypotension.
      Obstetric anaesthetists reported discussing a mean of 8.0 (SD 3.8) and 10 (SD
      3.8) risks in the labour and antenatal settings respectively. Nearly 20% of
      respondents did not rank post dural puncture headache among their top five most
      important risks for discussion. Seventy percent of respondents indicated that
      they believe active labour inhibits a woman's ability to give 'fully informed
      consent'. Over 80% of respondents obtain verbal consent and 57 (20%) have no
      record of the consent or its discussion. Obstetric anaesthetists reported making
      a considerable effort to inform patients of risks prior to the provision of
      regional analgesia in labour. Verbal consent may be appropriate for labouring
      women, using standardized forms that serve as a reminder of the risks, and a
      record of the discussion. Consensus is required as to what are the levels of risk
      from regional analgesia in labour.

PMID- 16617651
TI  - Anaesthesia medical workforce in New Zealand.
AB  - This survey was conducted in all 28 New Zealand District Health Boards with a
      response rate of 100%. The Clinical Directors of Departments of Anaesthesia were
      asked to quantify their current anaesthesia service delivery and to assess their
      workforce level. Over half of the District Health Boards reported understaffing,
      fifty percent occurring in hospitals of provincial cities or towns with an
      inability to attract specialist anaesthesia staff. Financial constraint was the
      other main reason for understaffing. With the information from the survey, an
      attempt was made to predict future New Zealand anaesthesia workforce
      requirements. A model for Australasia established by Baker in 1997 was used. In
      comparing this survey to previous studies, there is evidence that the nature and
      expectations of the anaesthesia workforce are changing as well as the work
      environment. Currently, there is no indication that anaesthesia specialist
      training numbers should be reduced. Close, ongoing monitoring and planning are
      essential to ensure future demands for anaesthesia services can be met.

PMID- 16617652
TI  - Pacemaker-driven tachycardia induced by electrocardiograph monitoring in the
      recovery room.
AB  - Monitoring devices are known to induce tachycardia in minute-ventilation rate
      responsive pacemakers. This is because some monitoring devices measure the same
      parameter as do the pacemakers (change in thoracic impedance). Hence, the
      biological signal to the pacemaker is increased and is misconstrued as increased
      minute ventilation causing tachycardia which resolves when the monitoring device
      is removed. Whilst this could occur for all minute-volume rate responsive
      pacemakers, most reported interactions have been with the Telectronics META
      series. We present a case of an interaction between a Telectronics Tempo DR
      pacemaker (St. Jude Medical) and an Agilent Patient Care System (Philips).
      Failure to recognise the true nature and cause of such tachycardias may lead to
      mismanagement of the patient, including the inappropriate use of cardio-active
      medications.

PMID- 16617653
TI  - Subdural spinal haematoma after epidural anaesthesia in a patient with spinal
      canal stenosis.
AB  - A 60-year-old male with a past history of T12 fracture had epidural analgesia for
      a radical prostatectomy. It was unknown prior to epidural insertion that the
      patient had a canal stenosis at T12 from the previous injury. The patient
      developed severe bilateral buttock pain after epidural catheter removal. Magnetic
      resonance imaging demonstrated a spinal subdural haematoma from T10 to L2 with
      mild cord compression. The patient made a successful recovery with conservative
      management. Neuraxial blockade should be approached with caution in patients with
      previous back injury, and only after a thorough assessment has been obtained to
      exclude spinal canal stenosis.

PMID- 16617654
TI  - Pneumothorax from intrapleural placement of a nasogastric tube.
AB  - Nasogastric tube insertion is a commonly performed procedure that can be
      associated with significant morbidity and even mortality. There is no universally
      accepted technique to confirm correct placement. Most confirmatory methods are
      performed after placement, therefore misplacement and potential complications may
      have already occurred. We report a case where a commonly used bedside
      confirmatory test gave false reassurance that the nasogastric tube was properly
      positioned, but a plain chest X-ray revealed a massive pneumothorax due to
      inadvertent intrapleural placement of the tube. Due to the deficiencies of
      traditional confirmatory bedside techniques, and the limitations of modern and
      more sophisticated confirmatory methods, the plain chest X-ray remains the gold
      standard test to confirm correct nasogastric tube placement. We appraise the
      methods commonly employed to confirm nasogastric tube placement, and discuss
      factors that may increase the risk of misplacement.

PMID- 16617655
TI  - Methylene blue for diagnosis of displaced atrial lines.
AB  - Methylene blue (aniline violet, tetra-methylthionine chloride) has several
      important uses in clinical medicine, including diagnosis of displaced central
      lines. After cardiac surgery, three infants with suspected displacement of direct
      atrial lines were given methylene blue. After injection of the dye into the
      atrial lines, bluish discolouration was identified in their chest drainage. Use
      of methylene blue in small amounts appears to be a safe and effective way of
      diagnosing extravasation of fluid from displaced central lines.

PMID- 16617656
TI  - Anaesthesia and medical student education.

PMID- 16617657
TI  - Misleading pulse-oximetry in a patient with tricuspid valve incompetence.

PMID- 16617658
TI  - Successful use of the classic LMA after failed use of the ProSeal LMA.

PMID- 16617659
TI  - Daclizumab in the induction phase of immunosuppression in heart transplant
      recipients.
AB  - OBJECTIVES: Acute rejection episodes negatively effect both short-term survival
      and development of graft vasculopathy. METHODS: We assessed the incidence and
      severity of acute rejection episodes under a new protocol using a monoclonal
      antibody daclizumab in the induction phase of immunosuppressive therapy. The
      study group B (26 patients) was given daclizumab (1 mg/kg), the control group A
      (25 patients) was treated without daclizumab. There was no significant difference
      between the two groups in the important data. A total of first 10 EMB in every
      patient was classified according to the ISHLT recommendation. We also analysed
      the incidence of infections. RESULTS: During the first two months there was a
      significant lower incidence and/or severity of rejection episodes in the
      daclizumab group with p < or = 0.0016, 0.001 and 0.005 respectively. CONCLUSIONS:
      Induction therapy with daclizumab significantly reduces the incidence of acute
      rejection episodes during the first two posttransplant months in heart transplant
      recipients. It does not increase the risk of infection.

PMID- 16617660
TI  - Prevention of hepatitis B recurrence after liver transplantation.
AB  - Over the last decade significant improvement in patient and graft survival has
      been observed after liver transplantation for hepatitis B virus (HBV)-related
      liver disease, mostly because of efficient prophylaxis against hepatitis B
      reinfection. This review discusses different approches in prevention of hepatitis
      B recurrence in liver recipients including new concepts as vaccination against
      hepatitis B after liver transplantation. Based on available data combined
      prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine is currently
      recommended prophylaxis for HBV recurrence after liver transplantation.

PMID- 16617661
TI  - The application of deep-frozen and radiation-sterilized human amnion as a
      biological dressing to prevent prolonged air leakage in thoracic surgery.
AB  - Amnion allografts have been used in a number of clinical applications. However,
      no references of their use in thoracic surgery have been identified. Air leakage,
      is one of the most common complications in thoracic surgery, resulting from
      visceral pleura and lung injuries caused intraoperatively, in particular
      following rethoracotomy. Mechanical and manual sutures are also potential sites
      of air leakage. The aim of our study was to evaluate the usefulness of human
      amnion grafts in the treatment of air leakage following thoracic surgery. Deep
      frozen, radiation-sterilized (35 kGy) human amnion grafts prepared in the Central
      Tissue Bank in Warsaw (Poland) were used. The amnion allografts were applied to
      20 patients who had surgery: 11 thoracotomies and 9 rethoracotomies were
      performed (15 resections of 1-12 metastases, 3 lobectomies and 2 residual tumor
      resections). During lung ventilation the air leakage sites were covered by the
      amnion flap attached by moderate compression and stabilized by sutures. Air
      leakage and drainage were measured during the postoperative period. In 80% of the
      cases, no traces of air leakage was observed. The preliminary results suggest
      that the application of human amnion grafts may be a safe and effective method
      for preventing prolonged air leakage after thoracic surgery.

PMID- 16617662
TI  - Biliary complications following adult liver transplantation with routine use of
      external biliary drainage.
AB  - OBJECTIVES: Biliary complications are still common and often related to the use
      of biliary drains in liver transplant setting. We analyzed the incidence,
      treatment and outcome of biliary complications following adult orthotopic liver
      transplantation (OLTx) performed between February 2002 and October 2004. METHODS:
      Overall there were 46 OLTx performed in 44 patients. Two cases of primary graft
      non-function (one re-graft) and 2 early postoperative deaths were excluded from
      the study resulting in 42 OLTx performed in 41 patients included in the final
      analysis. Biliary reconstruction was by duct-to-duct choledochocholedochostomy
      (DD, n = 37) and Roux-en-Y hepaticojejunostomy (RYHJ, n = 5) performed over an
      external Levin type biliary drain in all cases. RESULTS: The overall incidence of
      biliary complications was 28.6% (12/42). Bile leak was the commonest and occurred
      in 16.6% (7/42) of transplants, whereas biliary strictures were found in 3 (7.2%)
      patients. Eight (19%) patients required surgical treatment and one patient died
      due to a biliary complication (2.4% mortality rate). Majority (7/12) of
      complications were bile drain related and all of these occurred in patients with
      DD anastomosis. CONCLUSION: Biliary complications continue to cause significant
      morbidity after OLTx but rarely result in mortality if early diagnosis and prompt
      therapy is applied. Majority of biliary complications following DD anastomosis
      have been related to the use of biliary drains. In view of this and endoscopic
      expertise available, duct to duct anastomosis without a biliary drain may reduce
      complication rates and improve outcome.

PMID- 16617663
TI  - First two successful unrelated donor bone marrow transplantations for paroxysmal
      nocturnal hemoglobinuria in Poland.
AB  - OBJECTIVES: The experience with bone marrow transplantation (BMT) from matched
      unrelated donors (MUD) for paroxysmal nocturnal hemoglobinuria (PNH) is limited
      and optimal preparative regimen has been not established. METHODS: We report
      first two MUD BMTs for patients with PNH in Poland. Preparative regimen consisted
      of Treosulfan, Fludarabine and Thymoglobulin. We also present the review of
      published reports on allogeneic transplantations for PNH and discuss important
      transplant-related issues. RESULTS: Both patients are alive and are doing well
      over 12 and over 4 months following BMT. Regeneration is complete with full 100%
      donor chimerism and the eradication of PNH clone. CONCLUSIONS: MUD BMT is an
      effective treatment for PNH. Treosulfan, Fludarabine and Thymoglobulin treatment
      can be safely and effectively used for conditioning in PNH.

PMID- 16617664
TI  - The comparison of treatment results of type 1 diabetes mellitus complicated by
      end-stage diabetic nephropathy in patients undergoing simultaneous pancreas and
      pre-emptive kidney transplantation (SPPkTx) and patients enrolled into the
      dialysis program--a cohort study.
AB  - OBJECTIVE: A cohort study was conducted to compare treatment of patients with
      type 1 diabetes mellitus and end-stage diabetic nephropathy. PATIENTS AND
      METHODS: 47 type 1 diabetic patients required renal replacement therapy in years:
      2001-2005 were enrolled. Simultaneous pancreas and preemptive kidney transplant
      (sppktx) was performed in 18 (group I). Group II consisted of 29 patients who
      entered dialysis program. Survival rate for patients from both groups was
      estimated. Transplanted organ function was evaluated for group II. Lipid profile
      and its correlation with thickness of carotid media was assessed. Impact of
      sppktx on diabetic retinopathy was investigated. Cost and life quality were
      compared between groups. RESULTS: Two-year cumulative recipient survival rate for
      group I and II was 100% and 96%, respectively. One-year cumulative survival rate
      for transplanted pancreas was 88% and for kidney grafts 94%. In group I
      cholesterol and triglyceride level before transplantation were: 207 +/- 38 mg/dl
      and 133 +/- 65 mg/dl and decreased after transplantation to 155 +/- 20 mg/dl and
      78 +/- 25 mg/dl, respectively (p < 0.05). No difference of carotid media
      thickness was observed between groups. Stabilization of retinopathy was observed
      in 91.6% non-blind recipients. During the first year of the follow-up the costs
      of transplantation doubled those of dialysis therapy but in the second year the
      costs of dialysis exceeded the costs required for transplanted patients.
      CONCLUSION: Despite of major surgery and introduction of immunosuppression in
      group I, results did not differ significantly between groups during a two-year
      follow-up. After sppktx, stabilization of the carotid media was slower than the
      normalization of lipids. At the second year, transplantation is less expensive
      than dialysis.

PMID- 16617665
TI  - Our picks of big and not so big issues.

PMID- 16617666
TI  - Organ donation and procurement.

PMID- 16617667
TI  - What is new in clinical kidney and liver transplantation.

PMID- 16617668
TI  - What is new in heart transplantation.

PMID- 16617669
TI  - Post-transplant diabetes mellitus (PTDM) in heart recipients.
AB  - In conclusion, comparative clinical studies with tacrolimus in heart recipients
      tend to show a similar or increased diabetogenic potential compared with
      cyclosporine-ME-based therapy. However, these changes are often accompanied by a
      reduced effect on lipid metabolism and hypertension suggesting a superior
      cardiovascular risk profile. The superior control of acute rejection also
      positions tacrolimus as an attractive alternative to cyclosporine for heart
      recipients.

PMID- 16617670
TI  - Chronic renal failure in non-renal organ transplant recipients.
AB  - Recovery of the patients after transplantation of non-renal organs may be
      complicated by multi-faceted chronic renal failure (CKD) which is regarded as an
      independent risk factor of graft dysfunction and mortality. The occurrence of CKD
      in non-renal transplant recipients depends mainly on a type of transplanted
      organ, immunosuppressive protocol and pre-transplant kidney dysfunction. Several
      concomitant diseases including arterial hypertension, dyslipidemia, diabetes
      mellitus, hepatitis or perioperative renal injury may contribute to chronic
      kidney disease. Current data suggest that a problem of kidney insufficiency in
      non-renal organ transplant recipients may still be underscored. Clinicians ought
      be aware that renal dysfunction should be added to a list of major post
      transplant complications.

PMID- 16617671
TI  - Role of serotonin in cerebral oxidative stress in rats.
AB  - Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter
      synthesized by the aromatic amino acid decarboxylase using 5-hydroxytryptophan (5
      HTP) as a substrate. It was recently shown that serotonin and its precursor have
      powerful antioxidant properties. The aim of this study was to evaluate the effect
      of reduction in 5-HT levels by parachlorophenylalanine (pCPA) and their
      restoration by 5-HTP administration on lipid peroxidation and antioxidant status
      in rat brain. Serotonin levels were decreased by p-chlorophenylalanine
      administration. The effect of p-chlorophenylalanine was counteracted by the
      intraperitoneal administration of 5-hydroxytryptophan. We evaluated the
      concentration of serotonin, malonyl dialdehyde and the status of antioxidants
      (GSH, catalase and superoxide dismutase) in brain. The results showed that p
      chlorophenylalanine (300 mg/kg) induced a depletion of serotonin concentration
      and antioxidant status, as well as enhancing malonyl dialdehyde concentration in
      brain. The exogenous administration of 5-hydroxytryptophan prevented all effects
      induced by p-chlorophenylalanine in brain tissue. The recovery of the
      neurotransmitter concentration in brain was related to the reduction of lipid
      peroxide generation and improved antioxidant status. In conclusion, our study
      supports the view that the antioxidant properties of serotonin protect against
      basal oxidative stress in brain.

PMID- 16617672
TI  - Effects of postweaning social isolation and re-socialization on the expression of
      vasoactive intestinal peptide (VIP) and dendritic development in the medial
      prefrontal cortex of the rat.
AB  - In the present study we evaluated the effects of early social isolation and re
      socialization on dendritic development and the expression of the vasoactive
      intestinal peptide (VIP) in the medial prefrontal cortex (mPFC) of the rat.
      Sprague-Dawley male rats were reared either in isolation (IC) or social (SC)
      conditions from postnatal day 18 to 32. Rats were then behaviorally evaluated in
      the open field test, and approximately half of the animals were sacrificed. Their
      brains were processed either for immunocytochemical labeling against VIP or for
      the Golgi-Cox-Sholl staining. The remaining IC rats were re-socialized during 30
      additional days. The results demonstrated that early social isolation impair
      neuronal dendritic arborization and increase the number of VIP-immunoreactive
      neurons. Furthermore, animals displayed hyperlocomotion in the open-field test.
      According to our structural, immunocytochemical and open-field data, the
      resocialization experience was unable to reverse neuronal and behavioral
      abnormalities.

PMID- 16617673
TI  - Effect of 3-aminobenzamide on Bcl-2, Bax and AIF localization in hippocampal
      neurons altered by ischemia-reperfusion injury. the immunocytochemical study.
AB  - Poly(ADP-ribose) polymerase plays an important role in cell survival and death.
      Our previous histological and ultrastructural studies showed that PARP inhibitor
      3-aminobenzamide (3-AB) protected neurons against death after ischemia. In this
      study we investigated the effect of 3-AB on the localization and expression of
      apoptosis inducing factor (AIF) and on two proteins from Bcl-2 family: Bcl-2 and
      Bax in hippocampal area CA1, on the 4th day after 3 min of forebrain ischemia in
      gerbils. Our results indicated that after ischemia AIF is preferentially
      translocated from the mitochondria to the cytoplasm and to the nucleus.
      Intravenous administration of 3-AB (30 mg/kg b.w.) prevents AIF translocation to
      the nucleus. AIF was mainly seen in the structurally unchanged mitochondria and
      Golgi complex. Moreover, after 3-AB administration overexpression of Bcl-2
      protein was observed in mitochondrial membranes, rough endoplasmatic reticulum,
      Golgi complex, nuclear envelopes, and also in cytoplasm and in nucleus. These
      data suggest that inhibition of PARP activity may have a beneficial effect on
      hippocampal neurons through overexpression of Bcl-2 protein and suppression of
      AIF translocation to the nucleus.

PMID- 16617674
TI  - Acute effects of maprotiline on learning, anxiety, activity and analgesia in male
      and female mice.
AB  - The acute effects of maprotiline (2.5, 5, 10, 15, 20 or 25 mg/kg) on learning,
      anxiety, activity and analgesia in male and female mice were evaluated. In
      addition to inhibitory avoidance learning, anxiety and locomotor activity were
      measured in the same animals using an elevated plus-maze. A study of the acute
      effects of maprotiline (15, 20 or 25 mg/kg) on analgesia was carried out in naive
      animals of both sexes. Maprotiline impaired inhibitory avoidance at doses of 15,
      20 or 25 mg/kg. The highest dose produced an anxiolytic effect in females, and
      the doses of 20 and 25 mg/kg reduced locomotor activity. Analgesia was observed
      with the highest dose. The impairment of inhibitory avoidance by maprotiline
      would seem to be independent of the drug's influence on anxiety, is not shadowed
      by an instrumental performance deficit and, at least in the case of the highest
      dose, could be influenced by the drug's effects on analgesia. It is hypothesized
      that acquisition is the memory process principally affected by maprotiline, and
      in particular stimuli processing. The lack of sex differences in the effects of
      maprotiline on inhibitory avoidance supports the generalization of findings
      previously obtained only in males.

PMID- 16617675
TI  - The anatomical relationships between the serotonergic afferents and the neurons
      containing calcium-binding proteins in the rat claustrum.
AB  - Claustrum is a telencephalic structure integrating information of various
      modalities. Proper functioning of this structure depends on the presence of a
      network of intrinsic connections. This includes GABA-ergic neuronal populations
      that also contain calcium-binding proteins (CaBPs). The goal of this study was to
      analyze qualitative and quantitative the 5-HT-containing fibers in the rat
      claustrum and to assess the relationships between these fibers and the
      populations of claustral neurons expressing CaBPs. We used the methods of
      immunocytochemistry and morphometry. The serotonergic fibers in the claustrum are
      heterogeneous, both with respect to their morphology and spatial distribution.
      Thin varicose fibers are more numerous and are homogeneously distributed within
      the claustrum. Remaining fibers were thicker and possessed larger varicosities.
      They were present mainly in the ventral part of the claustrum. Although the
      serotonergic fibers are found in the vicinity of claustral cells containing
      CaBPs, direct contacts between these fibers and cells are rare. Other mechanisms,
      including volume transmission, may possibly mediate serotonergic influences.

PMID- 16617676
TI  - Stereotactic approach and electrophysiological characterization of thalamic
      reticular and dorsolateral nuclei of the juvenile pig.
AB  - Few reports exist on complex functions of pig's central nervous system. A direct
      access to thalamic structures enables a deeper understanding of neuronal
      networks. Here we present an easy to implement stereotactic approach to reach
      both reticular and dorsolateral thalamic nuclei (RTN and LD). In thirteen pigs (7
      weeks old) the correct electrode position was confirmed for 22 out of 26 thalamic
      electrodes (RTN: A+2, L9, V24 and LD: A-2, L5, V20, with bregma A 0, L 0).
      Quantitative effects of isoflurane/nitrous oxide (State 1) and fentanyl sedation
      (State 2) were determined by brain hemodynamics and metabolism. Neurophysiologic
      features were performed by spectral power, coherence and SEP analysis. Brain
      blood flow (by 21 +/- 13%) and oxidative brain metabolism (CMRO, by 26 +/- 12%,
      CMRGlucose by 26 +/- 22%) were markedly reduced during State 1 (P<0.05). Regional
      thalamic blood flow exhibited similar alterations, but side-differences did not
      occur. State 1 induced quite similar brain activity in cortical as well as
      thalamic regions investigated. During State 2 electrocortical activity of low
      frequency ranges was markedly reduced, whereas spectral band power of high
      frequency ranges was additionally decreased in RTN (P<0.05). Thus, we used a
      convenient approach for targeted deep electrode implementation and characterized
      electrophysiological features in RTN and LD.

PMID- 16617677
TI  - Prosodic pitch accents in language comprehension and production: ERP data and
      acoustic analyses.
AB  - We used event-related potentials (ERPs) and acoustic analyses to investigate the
      processing of prosodic pitch accents as a function of their position in a
      sentence. Accents in sentence-medial positions were characterized by a higher
      fundamental frequency (F0) and an increased duration. They elicited two different
      negative ERP components around 400 ms, depending on the predictability of the
      accent. When the accent was predictable, the negativity was fronto-laterally
      distributed and identified as the previously known Expectancy Negativity.
      Unpredictable accents elicited a more broadly distributed N400 with a central
      maximum, reflecting difficulties in semantic processing. For sentence-initial
      pitch accents, words had a higher F0 but of the same duration as sentence-initial
      words without pitch accents. These pitch accents elicited a P200 but no
      negativity in a 400 ms time window. The P200 was modulated by the onset latency
      of the F0 peak rather than its magnitude. We discuss the possibility of a delayed
      processing of sentence-initial accents when the actual occurrence of an F0 peak
      can be identified by comparing the F0 of the sentence-initial word to a reduced
      F0 of a word occurring later in the sentence.

PMID- 16617678
TI  - Visceral signals reach visual cortex during slow wave sleep: study in monkeys.
AB  - Propagation of signals from the gastro-intestinal system towards the occipital
      cortex within sleep-wake cycle was investigated in three monkeys used in the
      study of sleep impairment in a chronic MPTP model of parkinsonism. The monkeys
      differed in motor abilities and sleep structure. e animal (M1) was non-motor
      disabled and had no sleep alterations. The other two monkeys were severely motor
      affected, but one (M2) had normal sleep cycles; meanwhile, the other (M3) had no
      complete sleep cycles. To evaluate the level of sleep and to record cortical
      evoked responses screw electrodes were implanted over the occipital cortex. Two
      hours before overnight recordings, two hook electrodes were injected
      intraperitoneally (under light Ketanest anesthesia) and anchored in gut. Using
      these electrodes, electric stimulation was applied during slow wave sleep, and in
      wakefulness. Cortical evoked responses to intraperitoneal stimulation were found
      indeed during sleep in experiments with M1 and M2. These results show that also
      in primates with normal sleep pattern visceral information is transferred to the
      cerebral cortex during slow wave sleep.

PMID- 16617679
TI  - Jerzy Konorski on brain associations.
AB  - Jerzy Konorski (1903-1973) exerted a vital influence on the development of
      physiological psychology and neurobiology. Konorski and his friend and
      collaborator, Stefan Miller, distinguished instrumental conditioned reflexes as a
      separate type of acquired behavior, different from classical (Pavlovian)
      conditioned reflexes. In a series of pioneering studies Konorski demonstrated
      basic differences between the two types of conditioned reflexes. After the Second
      World War, he reinterpreted the results of research on conditioned reflexes on
      the basis of the mechanisms of Sherringtonian neurophysiology and introduced the
      term plasticity of the nervous system. His work, "Conditioned reflexes and neuron
      organization", published in 1948, signaled Konorski's place as one of the
      founders of contemporary neuroscience. He contributed significantly to the
      understanding of complex interactions of various classes of behaviors: innate and
      acquired, those driven by opposite motivations, and those elicited by cues
      signaling different contingencies. In his book "Integrative activity of the
      brain" (1967), Konorski analyzed the brain as a complex system directing the
      functioning of the organism as a whole.

PMID- 16617680
TI  - Konorski and conditional reflexes: a historical summary and an addendum.
AB  - There have been four major pioneers from Eastern Europe in the neuroscientific
      study of memory and learning: Pavlov, Bekhterev, Beritashvili and Konorski. The
      thinking of each evolved with the progress of neuroscientific knowledge
      throughout the world, and save for Pavlov, each encountered governmental
      opposition to their views. Among the clues largely overlooked in their
      examination of conditional reflexes was the fact that the animal appreciates not
      only its own appetitive state but its immersion in the experimental setting. The
      latter in itself must require considerable, ongoing neuronal activity to sustain
      it. There is also the question as to whether "motivation" is an essential feature
      for the formation of conditional connections; and in cases where it is seemingly
      absent, as in recognition memory, the processes that underlie the astonishing
      efficacy of such memory formation remain almost wholly obscure. Finally, it is
      remarked that the cerebral cortex, as initially supposed, may indeed be the
      governing locus, even of such simple effects as habituation.

PMID- 16617681
TI  - Effects of granulocyte-colony stimulating factor on cardiac remodeling after
      myocardial infarction.
AB  - BACKGROUND: Recent studies suggest that granulocyte colony-stimulating factor (G
      CSF) may be beneficial in the treatment of myocardial infarction (MI). However,
      the effects of G-CSF on MI are still controversial and the molecular mechanism of
      G-CSF treatment for repair of the infarcted heart is not fully understood.
      METHODS: Mice were divided into three groups: Control, MI and MI treated with G
      CSF. Four weeks after MI, we examined cardiac function by Doppler
      echocardiography and measured non-infarcted myocardial mRNA expression by
      northern blot analysis. RESULTS: Cardiac function decreased significantly in the
      MI groups compared with the sham-operated groups. Additionally, the ratios of E
      wave to A wave peak velocity (E/A) in the MI groups were higher than in the
      control group. E/A in G-CSF MI mice was significantly lower than in control MI
      mice (p<0.01). Matrix metalloproteinase-2 (MMP-2) mRNA expression was
      significantly increased in the MI groups compared with the control group
      (p<0.01). Furthermore, mRNA expression in the G-CSF MI group was significantly
      higher than in the Control MI group (p<0.05). CONCLUSIONS: G-CSF can prevent the
      LV remodeling process after MI that accompanies progressive cardiac dysfunction.
      One of the mechanisms of G-CSF treatment for cardiac remodeling after MI may be
      overexpression of MMP-2 in non-infarcted myocardium.

PMID- 16617682
TI  - Inhibitory effects of environmental chemicals on protein disulfide isomerase in
      vitro.
AB  - BACKGROUND: The influence of endocrine disrupting chemicals (EDCs) upon
      physiological functions and their mechanisms is of concern. We have previously
      demonstrated that protein disulfide isomerase (PDI) was a target molecule of
      bisphenol A (BPA), which is considered to be EDC. PDI plays a key role in protein
      folding as an isomerase and also possesses a 3,3',5-triiodo-L-thyronine (T3)
      binding activity. Since PDI activities were inhibited by BPA in our previous
      study, BPA might have adverse effects on physiological functions via the
      inhibition of PDI activities. We conducted this study to identify the compounds
      which disturb PDI activities as well as BPA, and to discuss their structural
      characteristics. METHODS: We examined the effects of 22 suspected EDC on both the
      T3-binding activity and isomerase activity of rat recombinant PDI. RESULTS: Among
      the 22 compounds, only phenolic compounds, namely BPA, p-octylphenol, p
      nonylphenol, 2,4-dichlorophenol, pentachlorophenol, tetrabromobisphenol A, and
      tetrachlorobisphenol A, inhibited T3 binding to PDI. Furthermore non-halogenated
      compounds among these phenolic compounds, such as BPA, p-octylphenol, and p
      nonylphenol, showed inhibitory effects on the isomerase activity of PDI.
      CONCLUSIONS: Our results suggest that phenolic groups might have important
      inhibitory effects on the T3-binding activity of PDI, and that compounds with
      phenolic groups might have the same effects on PDI. Furthermore, non-halogenated
      phenolic compounds had inhibitory effects on the isomerase activities of PDI in
      addition to T3-binding activity, indicating that these compounds might also have
      adverse effects on protein folding, which PDI participates in by catalyzing
      rearrangements of disulfide bonds as an isomerase.

PMID- 16617683
TI  - Evaluation of peripheral muscle oxygenation during exercise by spatially resolved
      spectroscopy in patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Spatially resolved (SR) spectroscopy has enabled non-invasive and
      continuous measurement of muscle oxygen saturation during exercise. In patients
      with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction
      has been widely studied histochemically and biochemically. However, impairment of
      muscle oxygenation during exercise has not been elucidated yet. METHODS: We
      measured oxygen saturation in the vastus lateralis muscle (SmO2) using SR
      spectrometry during incremental cycle exercise in 16 COPD patients and 10 age
      matched healthy subjects. RESULTS: Significant decrease in SmO2 was found at peak
      exercise compared with warm-up in both groups (56.9 +/- 6.0% to 47.3 +/- 6.8% in
      patients with COPD, p<0.001; 60.7 +/- 5.8% to 49.9 +/- 7.7% in healthy subjects,
      p<0.01). The decrease in SmO2 was linear with respect to increase in work rate,
      and the slope of SmO2 was significantly steeper in COPD patients than in healthy
      subjects (-0.282 +/- 0.159 vs -0.107 +/- 0.057 %/Watt, p<0.001). The slope of
      SmO2 in COPD patients significantly correlated with body mass index (BMI)
      (p<0.01), peak percutaneous oxygen saturation (p<0.05), and peak pulmonary oxygen
      consumption (p<0.05). Stepwise regression analysis revealed that BMI was a
      significant determinant of the SmO2 slope (p=0.01). CONCLUSIONS: We conclude that
      oxygenation of peripheral muscle is impaired during exercise in COPD patients and
      that BMI contributes independently to the change of muscle oxygen saturation with
      exercise in COPD patients. SR spectroscopy will provide useful information for
      the study of the dynamics of muscle oxygenation in COPD patients.

PMID- 16617684
TI  - The optimal method for recording prosthetic heart valve sounds in clinical
      situations.
AB  - BACKGROUND: Valve sounds are thought to be useful in evaluating the functioning
      of prosthetic heart valves. In previous reports, two recording instruments have
      mainly been used, a condenser microphone (instrument A) and an accelerometer
      (instrument B), respectively. This study aimed to investigate the applicability
      of these conventional devices in recording mechanical heart valve sounds in daily
      clinical situations. In addition, two other instruments, namely, a stethoscope
      including a small microphone in its tube (instrument C) and an electrostethoscope
      (instrument D), were proposed and examined. METHODS: Mechanical valve sounds were
      recorded from postoperative patients using each-device and the signal to noise
      ratio (SNR) of each was calculated. Frequency characteristics of the two newly
      proposed instruments were also investigated by recording a sweep signal in an
      anechoic chamber. RESULTS: The SNR values of the new instruments were
      significantly superior to those of conventional ones (A, sound signals were not
      defined from noises; B, 0.97 +/- 0.59 dB; C, 11.5 +/- 4.7 dB; and D, 9.4 +/- 3.5
      dB, respectively p<0.05). The frequency characteristics of the two newly proposed
      instruments were also shown to be acceptable (under 10 kHz), though resonance
      frequency peaks were observed. CONCLUSIONS: Two newly proposed instruments can
      record mechanical heart valve sounds more noiselessly and with more ease than
      previous ones, and their frequency characteristics are acceptable.

PMID- 16617685
TI  - Cord blood transplantation for adult patients with hematological malignancies.
AB  - BACKGROUND: Recently, clinical studies of cord blood transplantation (CBT) in
      adults after myeloablative or nonmyeloablative conditioning regimens showed cord
      blood (CB) could effectively restore hematopoiesis and was associated with
      acceptable levels of graft versus host disease (GVHD). METHODS: This study
      reports the results of cord blood transplantation in 7 adults with hematological
      malignancies. RESULTS: Median age was 56 years (range, 43-69 years). HLA match
      was 4 of 6 in 4 cases and 5 of 6 in 3 cases. Median nucleated cell dose was 2.74
      x 10(7) cells/kg (range, 2.13-3.80) and CD34+ cell dose was 1.15 x 10(5) cells/kg
      (range, 0.44-2.79). Three patients had primary graft failure. There was one early
      death at day 24 after CBT due to pneumonia. Three patients with engraftment are
      alive and free of disease at day 390, day 348 and day 164 after CBT. Acute GVHD
      grade II occurred in 2 cases with engraftment, and chronic GVHD occurred in 1 of
      3 evaluable patients. Six patients with and without engraftment received more
      than 2.0 x 10(7) cells/kg nucleated cells. Three patients without engraftment
      received CD34+ cell dose less than that of 3 patients with engraftment.
      CONCLUSIONS: It is considered that graft CD34+ cell dose besides nucleated cell
      dose is important for engraftment. We believe that adult patients without
      suitable related or unrelated bone marrow donors should be considered as
      candidates for CBT by the choice of CB including both sufficient nucleated cell
      dose and CD34+ cell dose.

PMID- 16617686
TI  - Surgical management of bilateral adrenal metastases from hepatocellular carcinoma
      after transcatheter arterial embolization.
AB  - Despite progress in therapy for hepatocellular carcinoma, management of
      extrahepatic metastatic lesions remains problematic. A 73-year-old man who
      underwent transcatheter arterial embolization for hepatocellular carcinoma
      presented bilateral adrenal metastases. Ten months after transcatheter arterial
      embolization, computed tomography detected huge tumors in both adrenal glands.
      Simultaneous resection of both adrenal lesions was performed under hydrocortisone
      replacement therapy. These tumors were confirmed histopathologically to represent
      adrenal metastatic lesions of hepatocellular carcinoma. The patient died of
      respiratory failure due to lung metastasis 9 months after adrenalectomy, although
      intrahepatic tumor was controlled by transcatheter arterial embolization. It is
      necessary to clarify the therapeutic effectiveness and the indication of
      adrenalectomy for patients with adrenal metastasis.

PMID- 16617687
TI  - Electroacupuncture enhances striatal neurogenesis in adult rat brains after a
      transient cerebral middle artery occlusion.
AB  - In this study, we investigated the effects of electroacupuncture (EA) on ischemia
      induced neurogenesis in the striatum of adult rat brains with a 30-minute middle
      cerebral artery occlusion. Injection of bromodeoxyuridine (BrdU, 30 mg/kg, i.p.,
      cell proliferation marker) and 1,1'-dioctadecyl-6,6'-di(4-sulfophenyl)-3,3',3',3'
      -tetramethylindocarbo-cyanine (DiI, 1 microg/ microl, i.c.v, lipophilic neuronal
      tracer) combined with multiple fluorescence immunostaining were used to determine
      whether the proliferated cells were newly generated neurons and where they
      originated from in the brain. We demonstrated that EA treatment (60 Hz 1 s and 2
      Hz 3 s alternately at an intensity of 10 mA for 20 min on "Fengfu", GV.16 and
      "Jinsuo", GV.8) enhanced stroke-induced striatal neurogenesis in rat brains as
      follows: 1) EA increased the number of BrdU+ cells, indicating that it activates
      cell proliferation; 2) EA increased BrdU+/CRMP-4(+) (collapsing response mediated
      protein-4, immature neuron marker) and BrdU+/MAP-2(+) (microtubule-associated
      protein 2, mature neuron marker) cells, suggesting that it facilitates
      neurogenesis and maturation of newly generated neurons; 3) EA expanded the
      distribution of DiI-stained cells in the striatum. Moreover, most BrdU+/CRMP-4(+)
      or BrdU+/MAP-2(+) cells in the striatum were observed DiI+ staining. Thus, the
      results suggest that striatal newborn neurons mainly migrate from the cells
      lining ventricle. Therefore, we conclude that EA can improve neuronal
      regeneration, newborn neuron migration and their maturation in the striatum of
      adult rat brains after stroke.

PMID- 16617688
TI  - An exploratory study of the relationship between the midday-midnight law and
      electrical conduction properties of corresponding acupuncture points.
AB  - The midday-midnight law is a well-known empirical law in Oriental medicine
      stating that the circadian rhythm of internal organs influences their paired
      organs according to the time of day. However, there has been little research to
      test the purported relationship between the time of day and organ function. The
      purpose of this preliminary study was to investigate whether the midday-midnight
      law applies to the meridian activity and the electrical conduction properties of
      the acupuncture points. We used the digital readout instrument (MERIDIAN) to
      measure electrical conduction properties at 12 acupuncture points corresponding
      to the 12 meridians at four times: 12:00, 14:00, 22:00, and 24:00 hours. There
      were no significant differences in the electrical current values measured at the
      four times in any meridian. However, the mean current values of 12 acupuncture
      points changed significantly over time (P < 0.0001). The mean current values were
      significantly higher at 14:00 (P < 0.001), 22:00, and 24:00 hours (P < 0.001)
      than at 12:00 hours. The highest current value occurred at 22:00 hours and was
      significantly higher than 24:00 hours (P < 0.05). Although these do not
      conclusively support the traditional midday-midnight theory, our data suggest the
      existence of some type of daily variability in electrical current.

PMID- 16617689
TI  - Electro-acupuncture improves epileptic seizures induced by kainic acid in taurine
      depletion rats.
AB  - Electro-acupuncture (EA) partially inhibited epilepsy with great success. The
      biological basis underlying EA anti-convulsion remained uncertain, which resulted
      in limited application and slow improvement of acupuncture. Our previous study
      indicated that taurine may play an inhibitory role against epilepsy as an
      inhibitory amino acid in the central nervous system and EA may inhibit epilepsy
      via up-regulating the expression of taurine transporter to increase the release
      of taurine. Involvement of taurine in kainic acid (KA)-induced epilepsy and anti
      convulsion of EA was further addressed on taurine deficiency animal in the
      present work. We instituted endogenous taurine-deficiency model by
      supplementation of beta-alanine (3%) in drinking water for continuous 10 days
      initially, injected KA into lateral cerebral ventricle to induce epileptic
      seizure, and performed EA treatment on DU26 "RenZhong" and K "YongQuan" acupoints
      by an EA apparatus (Model G6805-2) using successive waves with the frequency 64Hz
      and the current intensity 0.8-1.0 mA for 30 minutes in Sprague-Dawley (SD) rats.
      Taurine levels markedly decreased in cortex, hippocampus, striatum and cerebellum
      of rats after beta-alanine administration by fluore-HPLC measurement. EA
      alleviated epileptic activity in rats at 3.5 h time point after KA injection,
      whereas beta-alanine-induced taurine depletion rendered rats more susceptible to
      KA-induced epilepsy. Taurine transporter level increased after EA treatment.
      These results suggested that taurine participated in epileptogenesis and EA may
      be related to taurine in controlling epileptic seizure.

PMID- 16617690
TI  - Beneficial effects and side effects of DHEA: true anti-aging and age-promoting
      effects, as well as anti-cancer and cancer-promoting effects of DHEA evaluated
      from the effects on the normal and cancer cell telomeres and other parameters.
AB  - The author evaluated the effects of DHEA (Dehydroepiandrosterone) on the amount
      of telomeres of normal cells and cancer cells and found the following: Contrary
      to the literature, which often recommended 25-50 mg of DHEA daily for the average
      adult human being, the author found that, depending on the individual, the
      maximum increase of normal cell telomere was obtained by a single optimal dose of
      1.25-12.5 mg. This was examined in 50 people, both males and females, between the
      ages of 20-80 years old. When one optimal dose was given to each individual, the
      average telomere amount in normal tissues, measured in Bi-Digital O-Ring Test
      units, often increased from anywhere between 25-300 ng to between 500-530 ng.
      Cancer cell telomere reduced from higher than 1100 ng to less than 1 yg (=10(-24)
      g) with equally significant normalization of abnormal cancer parameters (such as
      Integrin alpha5beta1, Oncogen C-fosAb2, Acetylcholine, etc.). Circulatory
      improvement and an increase in grasping force of up to 25% were also detected,
      along with the changing of a few white hairs to black hairs. The beneficial
      effects of one optimal dose of DHEA generally lasted between 1 to 4 months,
      though in some individuals it lasted for a much shorter period of time due to a
      number of negative factors such as excessive stress/work, excessive exposure to
      low temperatures and toxic substances, or use of common pain medicines. On the
      other hand, if a patient took an excessive dose of DHEA, the amount of normal
      cell telomere decreased, while there was an increase in cancer cell telomere. It
      was found that those who took an overdose of 25-50 mg daily for more than 3
      months had a high incidence of cancer of the prostate gland, breast, colon, lung,
      and stomach. Also, when the average normal cell telomere levels were less than
      110 ng, compared with a normal value of 120-130 ng, and when DHEA in different
      parts of the body was also extremely low (less than 1-2 ng), one could suspect
      the possible presence of a malignant tumor somewhere in the body. When normal
      cell telomere was less than 110 ng, most individuals felt very weary with marked
      tiredness in the eyes, and grasping force was often reduced.

PMID- 16617691
TI  - Effects of acupuncture on nNOS and iNOS expression in the rostral ventrolateral
      medulla of stress-induced hypertensive rats.
AB  - This study was to observe the changes of the neuronal and inducible nitric oxide
      synthase (nNOS & iNOS) as well as their mRNAs in the rostral ventrolateral
      medulla (RVLM) of stress-induced hypertensive rats before and after acupuncture,
      and thereby to infer the curative mechanism of acupuncture on hypertension. The
      result indicated that the systolic blood pressure (SBP) of stress group rats was
      increased significantly (P < 0.01), it was accompanied that the expression of
      nNOS in the RVLM, including the immunoreactive neuron number (P < 0.05), the
      optical density (OD) (P < 0.01), and the mRNA (P < 0.01) were obviously elevated,
      while those of iNOS (P < 0.05, P < 0.01 and P < 0.01) were evidently lowered in
      the stress-induced hypertensive rats. Electroacupuncture (EA) points at "Zusanli"
      (St. 36) and "Lanwei" (Extra 37) on the same hindlimb were stimulated by an EA
      apparatus (Type G6805-2) with dense sparse wave (4-20Hz) and 4mA intensity. EA
      application could return the SBP (P < 0.05), and the changes on the expression of
      both nNOS and iNOS (P < 0.05, P < 0.01 and P < 0.01). These results suggest that
      the curative mechanism of acupuncture on stress-induced hypertension is related
      to the changes of nNOS and iNOS in the RVLM of rats.

PMID- 16617692
TI  - Evaluation of electroacupuncture on ovariectomized rats: implications of modern
      scientific mechanisms on acupuncture curing woman perimenopausal syndrome.
AB  - Acupuncture has been used for treatment of female reproductive disorders dated
      back at least 2000 years. It has been known to promote homeostasis, modulate
      hormonal disturbance and induce ovulation. While the increasing popularity of
      acupuncture therapy demands a serious debate about its scientific documentation.
      This article is intended to present the experimental data about the effects of
      electroacupuncture at Guanyuan (RN 4), bilateral Zhongji (RN 3), Sanyinjiao (SP
      6) and bilateral Zigong (EXCA 1) in the ovariectomized rats. The EA stimulation
      produced from a Model G6805-H EA apparatus, and the stimulation parameters were
      frequency of 3Hz and intensity about 1-2mA, which was progressed in recent years
      by our group, so as to provide preliminary scientific background of acupuncture
      therapy of female perimenopausal syndrome.

PMID- 16617693
TI  - Detection and serotype-specific differentiation of vesicular stomatitis virus
      using a multiplex, real-time, reverse transcription-polymerase chain reaction
      assay.
AB  - A multiplex, real-time reverse transcription-polymerase chain reaction (RT-PCR)
      assay was developed that allowed simultaneous detection and rapid differentiation
      of vesicular stomatitis virus strains--New Jersey (VSV-NJ) and Indiana 1, 2, and
      3 (VSV-IN1-3). This assay involves use of a set of VSV universal primers located
      in the L gene that amplify VSV-IN1-3 and VSV-NJ using probes that allow
      differentiation of the major serotypes Indiana and New Jersey. The assay was
      evaluated using reference VSV, foot-and-mouth disease virus, swine vesicular
      disease virus, and vesicular exanthema of swine virus. To estimate diagnostic
      sensitivity, 159 epithelial samples collected between 1996 and 2002 from
      naturally infected cattle in Colombia were used. The assay cut off was calculated
      by testing RNA extracted from 150 virus-negative bovine tissues consisting of
      tongue, soft palate, muzzle, coronary band, and lymph node. All infected cattle
      were test positive for VS by results of real-time RT-PCR analysis; results for
      156 of 159 (98.1%) agreed with the serotype determination from the complement
      fixation test. Amplification did not occur in any of the negative bovine
      epithelial samples, allowing the cut-off values for the assay to be set. The real
      time RT-PCR assay was documented to be sensitive and specific for the detection
      of VSV-NJ and VSV-IN (1-3) strains from field samples in a single reaction,
      thereby supporting use of this assay in the differential diagnosis of vesicular
      virus diseases in cattle.

PMID- 16617694
TI  - Comparison of two automated immunohistochemical procedures for the diagnosis of
      scrapie in domestic sheep and chronic wasting disease in North American white
      tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus).
AB  - Two commercially available automated immunohistochemistry platforms, Ventana
      NexES and DakoCytomation Autostainer Universal Staining System, were compared for
      diagnosing sheep scrapie and cervid chronic wasting disease. Both automated
      platforms used the same antiprion protein monoclonal primary antibodies, but
      different platform-specific linker and amplification reagents and procedures.
      Duplicate sections of brainstem (at the level of the obex) and lymphoid tissue
      (retropharyngeal lymph node or tonsil) from the same tissue block were
      immunostained for the comparison. Examination of 1,020 tissues from 796 sheep
      revealed 100% concordance of results between the Ventana NexES and DakoCytomation
      platforms for diagnosing sheep scrapie from lymphoid tissue (103/103 positive;
      405/405 negative) and brainstem (120/120 positive; 392/392 negative). Similarly,
      examination of 1,008 tissues from 504 white-tailed deer revealed 100% concordance
      between the Ventana NexES and DakoCytomation platforms for diagnosing chronic
      wasting disease from lymphoid tissue (104/104 positive; 400/400 negative) and
      brainstem (104/104 positive; 400/400 negative). Examination of 1,152 tissues from
      482 mule deer revealed a concordance of 98.6% in lymphoid tissue and 99.9% in
      brainstem between the Ventana NexES and DakoCytomation platforms for diagnosing
      chronic wasting disease. The results indicate equivalence or near equivalence
      between the DakoCytomation and Ventana NexES autostainer platforms for
      identification of the disease-associated prion protein (PrPd)-positive and PrPd
      negative brain and lymphoid tissues in sheep, white-tailed deer, and mule deer.

PMID- 16617695
TI  - Isolation and characterization of a Sagiyama virus from domestic pigs.
AB  - In 2002, a strain of Sagiyama virus (SAGV) designated ML/Taiwan/02 was isolated
      from farmed pigs in Taiwan. The nsP1 and E1 gene sequences of the ML/Taiwan/02
      strain shared 98.6 and 96.7% homology, respectively, with corresponding genes of
      a Japanese strain of SAGV. Nucleotide and amino acid sequence comparison revealed
      this strain of SAGV to be most closely related to Getah virus, as opposed to its
      current classification as a subtype of Ross River virus. To investigate the
      seroprevalence of SAGV infection in Taiwan, a total of 586 pig sera collected
      from 11 of 17 Taiwanese districts were tested for serum neutralizing antibodies
      (SNA) against SAGV. Results indicated that 51% of the samples had SNA titer > or
      = 4, and 40% had SNA titer > or = 48, indicative of repeated exposure to SAGV in
      the field. To study the pathogenicity of the ML/Taiwan/02 strain, this strain was
      experimentally inoculated into 4-week-old specific-pathogen-free pigs that were
      seronegative for SAGV. Viremia was detected during postinoculation days (PID) 2
      4, when the SNA titer was < or = 16. By PID 7, viremia was no longer detectable,
      coinciding with the increase of SNA titer to > or = 48. Clinical illnesses or
      remarkable lesions were not observed. To the authors' knowledge, this is the
      first reported isolation of a strain of SAGV from pigs in the field. The virus is
      experimentally nonpathogenic to pigs but is moderately widespread, most likely
      via repeated exposure to virus-carrying mosquitoes.

PMID- 16617696
TI  - Comparison of the polymerase chain reaction-restriction fragment length
      polymorphism pattern of the fiber gene and pathogenicity of serotype-1 fowl
      adenovirus isolates from gizzard erosions and from feces of clinically healthy
      chickens in Japan.
AB  - The fiber gene sequence and pathogenicity of the serotype-1 fowl adenovirus (FAdV
      1) isolated from gizzard erosions and from clinically normal chickens were
      compared among isolates. The FAdV-99ZH strain, which induced gizzard erosions,
      had a nucleotide sequence of the long fiber gene that was different from that of
      the Ote strain, which did not induce gizzard erosions. The differences could be
      distinguished by use of polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) analysis. The long fiber gene of 16 FAdV-1 isolates from
      gizzard erosions and 10 FAdV-1 isolates from the feces of clinically normal
      chickens was examined by use of PCR-RFLP analysis. All 16 FAdV-1 isolates from
      gizzard erosions had the same restriction patterns as those of strain 99ZH;
      however, 10 FAdV-1 isolates from normal chickens were classified into 3 groups.
      Specific-pathogen-free (SPF) chickens were inoculated orally with 2 FAdV-1
      isolates from gizzard erosions or 3 FAdV-1 isolates from clinically normal
      chickens to determine the pathogenicity of each strain. Two of 2 FAdV-1 isolates
      from gizzard erosions induced gizzard erosions. Two of 3 FAdV-1 isolates from
      normal chickens had the same PCR-RFLP patterns as those of the Ote strain, but
      did not induce any gizzard erosions. However, 1 FAdV-1 isolate from clinically
      normal chickens had the same PCR-RFLP pattern as that of strain 99ZH and induced
      gizzard erosions. These results indicate that there are FAdV-1 strains that have
      different pathogenicity; one strain induces gizzard erosions, and the other does
      not. Use of PCR-RFLP analysis of long fiber genes may be able to distinguish
      between these two strains.

PMID- 16617697
TI  - Identification and differentiation of European and African/Australian strains of
      Mycoplasma mycoides subspecies mycoides small-colony type using polymerase chain
      reaction analysis.
AB  - Mycoplasma mycoides subspecies mycoides small-colony type (M. m. m. SC) is the
      cause of the economically important contagious bovine pleuropneumonia. Isolates
      from Africa and Australia have previously been documented to have a fragment of
      approximately 8.84 kb, which is absent in European strains. A set of polymerase
      chain reaction (PCR) primers over this region was designed to identify M. m. m.
      SC isolates and separate European strains from those of Africa/Australia.
      Specificity of the PCR assay was achieved through the positioning of an
      oligonucleotide within the insertion sequence IS1296, upstream of this deletion,
      which then was paired with a reverse primer, upstream of the deletion, within the
      8.84 kb-deleted region or downstream of the deletion, generating fragments of 1.1
      kb (all M. m. m. SC strains), 1.4 kb (African/Australian strains only) and 1.3 kb
      (European strains only), respectively. Identification and differentiation was
      specific for DNA from M. m. m. SC with no amplification of DNA from other cluster
      members or closely related species. The PCR products did not require
      differentiation by use of a restriction endonuclease, and have potential for use
      in detection of this organism in clinical samples.

PMID- 16617698
TI  - Development of a polymerase chain reaction assay for the detection of antibiotic
      resistance genes in community DNA.
AB  - Many methods are used to detect antibiotic resistance genes in samples. The
      objective of the study reported here was to compare polymerase chain reaction
      (PCR) analysis of community DNA with fecal culturing for detecting antibiotic
      resistance genes in cattle samples. In the laboratory-based portion of this
      study, known concentrations of an Escherichia coli strain with 3 antibiotic
      resistance genes (cmy-2, flo, and cat) were added to feces from dairy cattle.
      These genes were used to assess the effect of various primer pairs, chromosomally
      versus plasmid-encoded genes, and gene copy number on the sensitivity of PCR
      amplification. Gene-specific PCR amplification was performed on the community DNA
      extracted from the feces. Feces were cultured for the inoculated strain. In the
      field-based portion of the study, 80 cattle fecal samples of unknown gene status
      were compared by use of similar methods. Culture and PCR amplification from
      community DNA extractions produced variable results, and this variability was
      most noticeable at dilutions that approached the detection limit of the assay.
      Typically, PCR amplification had a higher sensitivity than did culture for
      detecting the gene of interest. However, the sensitivity of culture was improved
      by plating on selective media containing antibiotics. The community DNA approach
      enables assessment of bacterial communities in complex samples such as feces, a
      task that can be prohibitive by budget or time constraints associated with
      culture methods. Through a strategic combination of culture and community DNA
      approaches, the relationship between specific selection pressures and the
      persistence and dissemination of specific resistance genes can be elucidated.

PMID- 16617699
TI  - Evaluation of five enzyme immunoassays compared with the cytotoxicity assay for
      diagnosis of Clostridium difficile-associated diarrhea in dogs.
AB  - Clostridium difficile-associated-diarrhea (CDAD) is a nosocomial infection in
      dogs. Diagnosis of this infection is dependent on clinical signs of disease
      supported by laboratory detection of C. difficile toxins A or B, or both, in
      fecal specimens via enzyme-linked immunosorbent assay (ELISA). Unfortunately, to
      the authors' knowledge, commercially available ELISAs have not been validated in
      dogs to date. We evaluated 5 ELISAs done on 143 canine fecal specimens (100
      diarrheic and 43 nondiarrheic dogs) and on 29 C. difficile isolates. The results
      of each ELISA were compared with the cytotoxin B tissue culture assay (CTA).
      Clostridium difficile was isolated from 23% of the fecal specimens. Eighteen of
      the 143 fecal specimens were toxin positive (15 diarrheic and 3 nondiarrheic
      dogs). On the basis of multiplex polymerase chain reaction (PCR) analysis for
      toxin-A and -B genes, 72% of the isolates were toxigenic. The carriage rate of
      toxigenic isolates in diarrheic dogs was higher than that in the nondiarrheic
      dogs; however, these differences were not statistically significant. A good
      correlation was found between CTA, PCR, and culture results. The ELISAs done on
      fecal specimens collected from diarrheic dogs had low sensitivity (7-33%). In
      contrast, ELISA for toxin A or B, or both, performed on toxigenic isolates had
      high sensitivity (93%). These results suggest that commercially available human
      ELISAs are inadequate for the diagnosis of canine C. difficile-associated
      diarrhea when tested on fecal specimens. In contrast, the Premier ToxinA/B and
      Techlab ToxinA/B ELISAs may be useful for the diagnosis of canine CDAD when used
      on toxigenic isolates.

PMID- 16617700
TI  - Evaluation of the gamma interferon ELISA in sheep subclinically infected with
      Mycobacterium avium subspecies paratuberculosis using a whole-cell sonicate or a
      johnin purified-protein derivative.
AB  - The aim of the study reported here was to estimate the sensitivity and
      specificity of the gamma interferon (IFN-gamma) ELISA for paratuberculosis in
      sheep using receiver-operating characteristic analysis. Bacteriologic culture of
      tissues was used to define the reference positive population (n = 33). Two
      reference negative populations were used: culture-negative sheep from infected
      flocks (n = 77), and sheep from noninfected flocks (n = 358). We also evaluated
      the accuracy of 2 Mycobacterium avium subspecies paratuberculosis (MAP) antigen
      preparations, a whole-cell sonicate (MpS) and a johnin purified-protein
      derivative (PPDj). The source of the reference negative sheep used in the
      analysis affected overall accuracy of the IFN-gamma ELISA. The area under the
      curve was 0.683 (95% confidence interval 0.574-0.787), using culture-negative
      sheep from infected flocks, was 0.831 (0.764-0.889), using sheep from noninfected
      flocks for the MpS, and was 0.809 (0.726-0.881) and 0.897 (0.862-0.925) for the
      PPDj, respectively. Using the MpS, the cut point that classified the most sheep
      correctly was an optical density reading of 0.20, for sensitivity of 40.7% (19.4
      57.6) and specificity of 88.7% (77.0-95.7) or 97.6% (93.04-99.5), depending on
      the reference negative population used. Using the PPDj, the cut point that
      classified the most sheep correctly was 0.25 for sensitivity of 66.7% (47.2-82.7)
      and specificity of 93.5% (85.5-97.9) or 98.3% (96.4-99.4), respectively. The PPDj
      was more accurate at identifying MAP-infected sheep than was the MpS (P = 0.034).

PMID- 16617701
TI  - Internal restriction sites: quality assurance aids in genotyping.
AB  - Improvements to restriction fragment length polymorphism (RFLP)-based genotyping
      assays currently used for detection of mutations responsible for bovine
      ferrochelatase and myophosphorylase deficiencies, and equine hyperkalemic
      periodic paralysis (HYPP) are described. Reports of sporadic inhibition of
      restriction enzyme activity suggest a critical factor in RFLP-based genotyping
      assays should be assurance that restriction enzymes perform to specification with
      every sample. The RFLP genotyping assays that use either a mismatched recognition
      sequence in one or both of the oligonucleotides, or incorporate a second native
      site within the PCR amplicon, provide the mechanism by which efficiency of
      restriction enzymes can be assessed with every sample. The outcome is
      confirmation of the activity of the discriminating enzyme regardless of genotype.

PMID- 16617702
TI  - Western blot immunoassay as a confirmatory test for the presence of anti
      Mycoplasma hyopneumoniae antibodies in swine serum.
AB  - A Western blot immunoassay (WBI) was developed as a confirmatory test for 2
      commercial Mycoplasma hyopneumoniae (Mhyo) ELISAs. The WBI detected at least 5
      antigen bands (150, 130, 74, 70, and 30 kDa) from Mhyo whole membrane proteins
      that were not present in the antigens prepared from M. hyorhinis and M.
      hyosynoviae. Among discrepant sera from vaccinated pigs (n = 17) and field
      samples (n = 91) assayed by WBI: 1) 2 of the ELISA-positive samples reacted with
      all 5 antigens bands; 2) all blocking ELISA-positive samples (n = 53) bound 150-,
      130-, 74-, and 70-kD antigen bands; and 3) all indirect ELISA-positive samples (n
      = 55) bound 150-, 130-, and 30-kD antigens. We conclude that the WBI targeting
      the top 4 antigen bands is a useful confirmatory test for samples initially
      screened using the commercial Mhyo ELISAs.

PMID- 16617703
TI  - Interstitial pneumonia in neonatal canine pups with evidence of canine distemper
      virus infection.
AB  - Four dead canine pups (5-12 days old) from 3 litters in Douglas County of north
      central Colorado were submitted to the Colorado State University Diagnostic
      Laboratory for necropsy. Pups were originally presented to the referring clinics
      for respiratory tract illness, with or without diarrhea. At necropsy, the lungs
      from all pups had similar lesions, including random foci of hemorrhage and
      failure to collapse on opening of the thoracic cavity. The lungs were
      histologically characterized by subacute interstitial pneumonia, with alveolar
      septa expanded by a histiocyte-rich infiltrate with a few lymphocytes and
      neutrophils. The alveolar spaces were filled with moderate amounts of
      proteinaceous fluid, foamy macrophages, and a few neutrophils. Lungs from 3 of
      the 4 pups were test positive for canine distemper virus (CDV) by use of reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis. Immunohistochemically
      stained lungs, including those from the pup that were CDV negative, by use of RT
      PCR analysis, were test positive for CDV antigen in bronchial and bronchiolar
      epithelial cells and in a few alveolar macrophages. Central nervous system
      lesions were not observed in any of the 4 pups. These cases represent an unusual
      presentation of canine distemper in neonatal pups marked by respiratory tract
      lesions without central nervous system involvement. Canine distemper should be
      considered in the differential diagnosis of neonatal canine respiratory tract
      illness.

PMID- 16617704
TI  - Detection and characterization of naturally acquired West Nile virus infection in
      a female wild turkey.
AB  - An adult female wild turkey exhibiting disorientation and failure to flee when
      approached was submitted to the Mississippi Veterinary Research and Diagnostic
      Laboratory. Gross pathologic examination revealed evidence of dehydration and the
      presence of modest numbers of adult nematodes in the small intestine. Histologic
      examination revealed extensive multifocal perivascular lymphocytic infiltration
      in brain, marked heterophilic hyperplasia in bone marrow, and multifocal
      interstitial lymphocytic infiltration in heart, pancreas, ventriculus, and
      skeletal muscles. West Nile virus (WNV) was isolated from the brain, lung, and
      kidney tissues using cultured Vero cells. Higher copies of viral RNA were
      detected from brain, lung, and kidney than from heart, liver, or spleen by
      quantitative real-time reverse transcription-polymerase chain reaction (RRT-PCR)
      analysis. Immunohistochemical (IHC) analysis detected WNV antigen in various
      tissues including neurons, kidney, respiratory tract epithelium, heart, and bone
      marrow. On the basis of the data from this investigation, it is concluded that
      WNV caused encephalitis along with many other pathologic changes in the affected
      wild turkey.

PMID- 16617705
TI  - Novel iridovirus in a nautilus (Nautilus spp.).
AB  - Intracytoplasmic inclusion bodies suggestive of iridovirus infection were
      observed in formalin-fixed, paraffin-embedded tissues from a nautilus (Nautilus
      spp.) that died without premonitory signs. Transmission electron microscopy
      revealed enveloped, hexagonal, viral particles that measured approximately 176 nm
      in diameter. Virions contained a dense central core and morphology typical of
      iridoviruses. Extracted DNA was amplified using primers homologous to conserved
      iridovirus sequences. The amplicons were cloned, sequenced, and determined to be
      approximately 60% similar to reported amphibian iridovirus sequences. A
      polymerase chain reaction-generated digoxigenin probe was used to detect viral
      nucleic acid in tissue sections by DNA in situ hybridization and high-affinity
      cytochemistry. The detected nucleic acid corresponded to the inclusion bodies
      observed microscopically. This represents a novel iridovirus of mollusks.

PMID- 16617706
TI  - Relationship between DNA ploidy and proliferative cell nuclear antigen index in
      canine hemangiopericytoma.
AB  - The mitotic index is reported to be correlated with recurrence, mean patient
      survival, and metastasis of canine hemangiopericytoma (CHP). However, to the
      authors' knowledge, studies investigating the parameters that can predict
      recurrence or metastasis of CHP with low mitotic index have not been done. To
      evaluate growth kinetics of CHP with low mitotic index, a retrospective analysis
      of the proliferative activity by antiproliferative cell nuclear antigen
      monoclonal antibody and DNA contents by flow cytometry (FCM) was performed with
      21 formalin-fixed and paraffin-embedded CHP samples. Of the 21 tumors evaluated
      by FCM, 6 (26.6%) were aneuploid tumors, and 15 (71.4%) were diploid tumors.
      There was significant correlation between the PCNA index and ploidy pattern. The
      diploid group had 39.1 +/- 9.2 PCNA index, whereas the aneuploid group's
      proliferative cell nuclear antigen (PCNA) index was 63.1 +/- 8.2. The diploid
      group had mean mitotic index value of 1.140 +/- 0.855, and the aneuploid group
      had a mean value of 1.067 +/- 0.767. From these results, the CHP samples with low
      mitotic index were classified into either the aneuploid group with higher PCNA
      index or the diploid group with lower PCNA index, suggesting that DNA ploidy and
      proliferative activity may give an indication about malignancy of CHPs with a low
      mitotic index.

PMID- 16617707
TI  - Direct identification of Ehrlichia canis by a novel polymerase chain reaction
      method and molecular analysis of the citrate synthase (gltA) gene from various
      Italian strains.
AB  - Fourteen blood samples collected from dogs that were seropositive for Ehrlichia
      canis were examined for the presence of the citrate synthase gene using a highly
      specific and sensitive novel polymerase chain reaction assay. The assay detected
      E. canis DNA in 3 dogs. The complete nucleotide sequence of the citrate synthase
      gene was determined in 2 of the test-positive samples, and represents the first
      sequence of the gene to be derived from Italian isolates. The sequence data
      displayed high identity (99.2%) between the geographically separated Italian
      samples and the Oklahoma strain of E. canis. The high-sequence conservation
      revealed by molecular analysis confirmed the usefulness of the citrate synthase
      gene as a target for detection of E. canis.

PMID- 16617708
TI  - Identification of pathogenic Leptospira strains in tissues of a premature foal by
      use of polymerase chain reaction analysis.
AB  - Studies were carried out to determine the cause of death in a prematurely born
      Thoroughbred foal that died 24 hours after birth. Necropsy revealed gross lesions
      suggestive of septicemia. A commercial Leptospira polymerase chain reaction (PCR)
      assay designed to specifically amplify the hemolysis-associated protein 1 (hap1)
      gene present only in pathogenic Leptospira strains detected the presence of
      Leptospira DNA in various tissues of the foal. Histologic examination of lung,
      liver, kidney, and myocardium revealed numerous spirochetes in Warthin-Starry
      stained tissue sections. Results of PCR analysis and histologic examination
      suggested a leptospiral infection in the newborn foal. At the moment of death,
      the infection coexisted with a streptococcal-associated aspiration
      bronchopneumonia and postpartum septicemia. These findings indicate that the PCR
      assay based on the amplification of the hap1 gene represents a useful tool for
      specific detection of pathogenic leptospira in field samples taken from horses.

PMID- 16617709
TI  - Streptococcus pneumoniae-associated cellulitis in a two-month-old Domestic
      Shorthair kitten.
AB  - An approximately 2-month-old, reproductively intact female Domestic Shorthair
      kitten was presented to the Mississippi Veterinary Research and Diagnostic
      Laboratory with a history of possible trauma to the left shoulder region while
      playing with children, and was found dead the following day. Marked swelling,
      with subcutaneous edema and hemorrhages, was observed in the left forelimb.
      Severe pleocellular, but largely suppurative cellulitis, fasciitis, and
      interstitial myositis with edema were observed microscopically in sections from
      the affected limb. Massive numbers of gram-positive diplococci also were
      observed. Other pathologic changes included moderate interstitial pneumonia, mild
      cholangitis, lymph node hemorrhage, gastrointestinal nematodiasis, mild
      enteritis, and mild interstitial nephritis. Bacteriologic culture identified
      Streptococcus pneumoniae as the causative agent, which was confirmed by
      polymerase chain reaction amplification of the pneumolysin gene from chromosomal
      DNA of the isolate.

PMID- 16617710
TI  - Extraskeletal osteosarcoma associated with retained surgical sponge in a dog.
AB  - Retained surgical sponges are usually discovered in the abdominal cavity,
      sometimes years after the surgical procedure, and the typical reaction is
      formation of a foreign-body granuloma, often called gossypiboma or textiloma. In
      this instance, an extraskeletal osteosarcoma, associated with the granulomatous
      reaction to a retained surgical sponge adjacent to the stifle, was diagnosed in
      an 11-year-old Labrador Retriever 9 years after repair of a ruptured cranial
      cruciate ligament. Radiographic detection of linear foreign material in the soft
      tissue mass was the basis for a diagnosis of gossypiboma. The mass was surgically
      excised. Histologically, fibers consistent with those of cotton gauze were
      associated with the granulomatous inflammation and the osteosarcoma. Amputation
      or radiation therapy was declined; the dog was treated conservatively with
      doxycycline and deracoxib. Three months after surgical excision, the dog was
      euthanized because of local recurrence of the mass along with lameness and
      decreased appetite.

PMID- 16617711
TI  - Peliod hepatocellular carcinoma in a domesticated ferret (Mustela putorius furo).
AB  - Peliod hepatocellular carcinoma was diagnosed in a domesticated ferret (Mustela
      putorius furo). The diagnosis was made using immunohistochemical analysis,
      histologic examination, and the accepted classification schemes based on
      histomorphologic features. Bilateral, adrenocortical hyperplasia also was
      evident. Speculation about a possible association between the variant of
      hepatocellular neoplasia diagnosed in this animal and its adrenal pathologic
      changes was done.

PMID- 16617712
TI  - The price of good intentions. Mo. hospital's asthma initiative aims to reduce
      unnecessary visits and save HMOs cash, but is it killing its own bottom line?
AB  - Jay Portnoy, left, chief of allergy, asthma and immunology at Children's Mercy
      Hospital in Kansas City, Mo., took multitasking to the next level with a special
      disease-management program that focuses on asthma. Since starting the program in
      2001, Children's Mercy has seen a huge decline in asthma-related ER visits and
      admissions. It's now selling its program to insurers.

PMID- 16617713
TI  - JCAHO keeps digging. Debate over patient-identifiable records continues.

PMID- 16617714
TI  - Legislation aims to improve IT. Senate and House bills press for codification,
      EMRs.

PMID- 16617715
TI  - Docs fall short. Lobbying efforts fail to rescind Medicare cuts with the clock
      still ticking.

PMID- 16617716
TI  - Measuring up. N. Y. execs concerned that rating system is a 'hit list'.

PMID- 16617717
TI  - Big spending. Calif. hospitals possibly wasting Medicare dollars: study.

PMID- 16617718
TI  - Growth opportunities. Construction, expansions won't overbed Denver.

PMID- 16617719
TI  - Dysfunctional relationship. Despite abuse, hospitals keep coming back for more
      from the Joint Commission.

PMID- 16617720
TI  - Front-page news. The media finally realizes patient safety is an important story.

PMID- 16617721
TI  - PBMs to the rescue? Pharmacy benefit managers will play a key role in the
      Medicare drug benefit. What does it mean for the industry, consumers and Uncle
      Sam?

PMID- 16617722
TI  - Ripe for scrutiny. In wake of probes, PBMs may draw extra attention.

PMID- 16617723
TI  - It takes a village. At dialysis provider DaVita, Kent Thiry would much rather be
      called mayor than CEO.

PMID- 16617724
TI  - Your move. Iowa doc group wants hospital to respond to lawsuit.

PMID- 16617725
TI  - [Tiotropium as new quality medication in the COPD management].
AB  - Chronic obstructive pulmonary disease (COPD) is heterogenous syndrome
      characterised by irreversible progressive airflow limitation caused mainly by
      tobacco smoking. In the continous bronchomotor tone of normal airways has a
      cholinergic component mediated via muscarinic cholinergic receptors. Cholinolitic
      bronchodilators act by blocking muscarinic receptors participate. Tiotropium
      bromide is an cholinolitic bronchodilatator that antagonises muscarinic receptors
      and dissociates more slowly from M1 and M3 than from M2 and subsequently has a
      long duration of action. Tiotropium reduces the number of exacerbations,
      increases time to first exacerbation and improves lung function significant
      compared with ipratiopium. Tiotropium produces superior bronchodilation,
      improvements in dyspnea, health related quality of life compared to ipratropium
      and salmeterol in patients with COPD. The use of tiotropium is associated with
      sustained reduction of lung hyperinflation at rest and during exercise.
      Tiotropium in combination with pulmonary rehabilitation produces clinically
      improvement in dyspnea, health status endurance of constant work compared to
      pulmonary rehabilitation alone. Many studies support the use of tiotropium once
      daily as first line maintenance treatment in patients with COPD.

PMID- 16617726
TI  - [The phenotypical review of patients with sleep apnea syndrome].
AB  - Sleep apnea syndrome (SAS) is common with obesity. This may be a risk factor for
      the evolution of hypertension, diabetes mellitus and other metabolic disorders.
      The aim of the study was to estimate, how is the frequency of adiposity, diabetes
      mellitus and hyperlipidemia by the SAS patients. Material and methods. On the
      basis of questionnaire SAS was suspected in 770 patients. The preliminary
      investigation was MESAM 4, and revealed 110 patients with desaturation during
      sleep. In all of them polisomnografic examination confirmed diagnosis. Glucose
      and lipides values and also description of: gender, age, and body mass index
      (BMI) was analysed. CONCLUSIONS: The analysis of the obtained results show the
      dependence of apnea-hypopnea index (AHI) and BMI, glucose and lipids values. The
      most frequent features in SAS patients is obesity, diabetes mellitus was the
      second one, hyperlipidemia was seldom observed.

PMID- 16617727
TI  - [The influence of body mass index on the patients with sleep apnea syndrome].
AB  - Obesity is a characteristic feature of patients with sleep apnea syndrome (SAS).
      The aim of the study was to show how obesity exerts an influence on the
      polisomnography results and other clinical feature in untreated SAS patients.
      MATERIAL AND METHODS: On the basis of SAS questionnaire SAS was suspected in 770
      patients. The preliminary investigation was MESAM 4, and revealed 110 patients
      with desaturation during sleep. In all of them polisomnografic examination
      confirmed diagnosis. The other performed investigations: spirometry and blood
      pressure during the day and polisomnografic examination. RESULTS: the analysis of
      the obtained results show the dependence of BMI on the polysomnographic study
      results, spirometry and blood pressure value. CONCLUSIONS: We observed that
      obesity is favorable to the development of: obstructive SAS, hypoventilation and
      desaturation during sleep, hypertension by SAS patients, SAS provoked disorders
      of sleep structure by all of the SAS patients.

PMID- 16617728
TI  - [Diagnostic validity of anti-tissue transglutaminase and anti-endomysium
      antibodies in children with celiac disease].
AB  - Tissue transglutaminase (tTG) plays a decisive role in the pathomechanism of
      celiac disease. Unchanged gliadin peptides bind to HLA-DQ2 with a week affinity,
      after that they are recognized by gliadin specific T-lymphocytes and the whole
      immune reaction is started which damages intestine mucous and causes the release
      of tTG. Tissue transglutaminase deaminates gliadin peptides enhancing the whole
      process. The aim of this study was determination of correlation between
      antiendomysial antibodies and anti-tissue transglutaminase antibodies in children
      with celiac disease, and the assessment of their usefulness in the diagnosis of
      celiac disease. MATERIAL AND METHODS: 109 children, aged 6 moths to 16 years
      (average 8.8 years) were included into the study. In all children an intestine
      biopsy was performed and/or antiendomysial antibodies were determined. In all
      children tissue transglutaminase antibodies were measured. Antibodies against
      tissue transglutaminase were determined using ELISA method. Antiendomysial
      antibodies were determined using the immunofluorescence method. RESULTS: In
      patients with normal mucous with lack of lymphocyte infiltration no IgAEmA were
      present in the blood. In the groups with subtotal and total villous atrophy all
      IgAEmA titres were positive. A positive titre of IgAEmA was observed only in
      childrerl with villous atrophy, which yields specificity of the test of 100%,
      sensitivity was 81%. Sensitivity of the anti-tTG antibodies test for detecting
      villous atrophy was 83% for IgA and 52% for IgG. There is a positive correlation
      between IgAEmA and anti-tTG antibodies. CONCLUSIONS: High sensitivity and
      specificity of determination of antibodies against tTG in IgA class causes that
      these tests may serve as a screening test in diagnosis and monitoring of celiac
      disease in children.

PMID- 16617729
TI  - [Intestinal complications and extraintestinal manifestations in children with
      inflammatory bowel disease].
AB  - In 15-20% of patients with inflammatory bowel disease (IBD) the disease starts
      during children period. The often observed consequences of the early start of the
      IBD are growth delay, undernutrition and pubertal delay. These problems are
      specific for pediatric population, in comparison with adults IBD patients. AIM:
      The assessment of the frequency and character of intestinal complications (IC)
      and extraintestinal manifestations (ElM) in children with IBD (ulcerative colitis
      - UC and Crohn disease - CD). MATERIAL AND METHODS: The frequency and character
      of IC and EIM in 184 children with IBD: 158 with UC (76 boys and 82 girls) aged
      from 2 to 18 years, and 26 with CD (14 boys and 12 girls) aged from 2 to 18 years
      were assessed. The frequency of IC and EIM in both groups of children Was
      compared statistically (chi-square test). RESULTS: Massive intestinal haemorrhage
      was observed in 11 children with UC. Perianal changes were present in 5 children
      with CD (significantly more often than in children with UC, p<0.05). External
      intestinal fistulae (p<0.0005), abdominal abscess, intestinal perforation and
      ileus (p<0.05) were characteristic complications of CD in comparison with UC. 50%
      of children with UC and 80% those with CD (statistically significant, p<0.005)
      had experienced, at least one ElM. Secondary anemia and growth delay were
      observed in 40,5% and 27,8% of children with UC and in 70% (p<0.05) and 80%
      (p<0.0001) of children with CD respectively. In children with IBD we observed
      also autoimmunologic hepatitis, primary sclerosing cholangitis, nephrolithiasis,
      pulmonary interstitial fibrosis, pancreatitis, neurological changes, skin
      manifestations and arthritis. Osteopenia was observed in 41% of children with CD
      and in 25% of children with UC. a CONCLUSIONS: A high prevalence of intestinal
      complications ane extraintestinal manifestations of IBD in pediatric population
      is observed. In children with IBD extraintestinal manifestations often occur
      before the onset of gastrointestinal symptoms. The presence of intestinal
      complications and extraintestinal manifestations in children with IBD should be
      considered during modification of therapeutic strategies.

PMID- 16617730
TI  - [An assessment of peripheral blood lymphocytes populations and subpopulation in
      patients with stomach cancer].
AB  - AIM: In the present study, we conducted the quantitative analysis of peripheral
      blood lymphocytes population and subpopulation in patients with stomach cancer,
      based on flow cytometry immunophenotyping. MATERIAL AND METHOD: The results were
      compared with the advancement of the disease (UICC/TNM), histological type
      (Lauren classification), and grade of differentiation of stomach cancer.
      Lymphocyte CD: (CD3/CD19, CD3/CD4, CD3/CD8, CD3/CD16, 56) were determined in 50
      cancer patients and 30 healthy humans. RESULTS: The significant deficiency of
      total lymphocyte number, T and B lymphocytes, as well as CD4+ and CD8+ was found
      in stomach cancer patients. There was no depletion in NK cells number. In
      advanced stomach cancer, the number of NK cells decreased, along with further
      deterioration of lymphocytes T and B populations. In patients with diffuse-type
      of stomach cancer and III or IV stage, the more pronounced deficiency in T, CD4+
      and CD8+ population was noted. The decrease grade of differentiation was
      correlated with the increase of NK cell population. There was no correlation
      between the number of B lymphocytes and the histologic type or grade of
      differentiation of stomach cancer. CONCLUSION: The obtained data demonstrated
      significant quantitative defect in defence of stomach cancer patients.

PMID- 16617731
TI  - [Evaluation of blood pressure changes by 24-hours ambulatory blood pressure
      monitoring (ABPM) in young, normotensive patients with diabetes mellitus type I].
AB  - The aim of this study was to evaluate usefulness of ambulatory blood pressure
      monitoring (ABPM) to examine circadian patterns of blood pressure (BP)
      alterations in young, normotensive patients with type I diabetes mellitus (DM1).
      MATERIAL AND METHODS: We studied 43 patients with DM1 aged 18-28 years, with 9-23
      years of DM1, without long-term complications. Control group consisted of 32
      healthy persons, matched to the DM1 group. 24h ABPM was performed by a Spacelab
      90207 device to obtain daytime (7 AM to 11 PM, readings at 20-min interval) and
      nighttime (11 PM to 7 AM, readings at 30-min interval) measurements in both
      groups. RESULTS: During the daytime systolic BP (sBP) and diastolic BP (dBP) were
      not significantly different from the control group. We noted nighttime sBP and
      dBP higher in DM1 group: sBE 119.7+/-12.6 mmHg vs. 103.817.1; p = 0.001 l dBP
      65.5+/-6.2 vs. 61.5+/-3.1; p = 0.001. The loss of fall in BP ('non-dippers') was
      more prevalent in DM1 group: 49% vs. 9%; p = 0.003. Pulse pressure (PP) was
      significantly higher in DM1 patients: 50.9+/-6.9 mmHg vs. 44.8+/-5.6 mmHg; p =
      0.0001. CONCLUSIONS: ABPM is a useful method in detecting early BP alterations in
      young normotensive patients with diabetes mellitus type 4 1. Increased PP and
      suppressed diurnal BP variations could represent a increased risk of
      cardiovascular complications in young patients with diabetes mellitus type 1.

PMID- 16617732
TI  - [Role of polymorphonuclear leukocytes in development vascular complications in
      diabetes].
AB  - Polymorphonuclear leukocytes (PMN) play role in the development of diabetic
      vascular complications. Activation PMN is associated with increased expression of
      adhesion molecules on the surface those cells. The aim of this study was to
      evaluate the expression of the beta2-integrin (CD11b/CD18) and selectin-L (CD
      62l) on the surface of the peripheral blood polymorphonuclear leukocytes in type
      2 diabetes with vascular complications. MATERIAL AND METHODS: The study was
      performed in a group of 36 type 2 diabetic patients that were subdivided into
      three groups: group A (n = 12, mean 56+/-5 years) - diabetes with early
      nephropathy (microangiopathy), group B (n = 12, mean 55+/-4 years) - diabetes
      with macroangiopathy, group C (n = 12, mean 56+/-4 years) - diabetes without
      vascular complications. Healthy individuals (n = 13, 54+/-5 years) who agreed to
      participate in the study served as controls. The expression of the CD11b antigen
      and CD62L antigen on the surface of the polymorphonuclear leukocytes was measured
      by flow cytometry. RESULTS: There was a significant increase in the expression of
      the CD11b antigen on the surface of the peripheral blood polymorphonuclear
      leukocytes from diabetic patient with early nephropathy (group A), when compared
      with healthy controls (7.8+/-2.4 vs. 3,8+/-0, 6; p<0.001) and diabetic patients
      without vascular complications (group C) (7.8+/-2,4 vs. 4.7+/-0.9; p<0.05). The
      expression of the CD11b antigen on the surface of the peripheral blood
      polymorphonuclear leukocytes from diabetic patient without vascular complications
      (group C) was also higher when compared with control group (4.7+/-0.9 vs. 3.8+/
      0.6; p<0.05). The expression of the CD11b antigen was similar on the
      polymorphonuclear leukocytes from patients with diabetic macroangiopathy and
      healthy individuals. There was no difference in expression of the CD62L antigen
      on the surface polymorphonuclear leukocytes in diabetic patients, when compared
      with control group. CONCLUSIONS: The results of this study show the activation of
      the peripheral blood polymorphonuclear leukocytes in type 2 diabetes. The
      expression of the CD11b antigen on the surface of the polymorphonuclear
      leukocytes is increased in patients with early diabetic nephropathy
      (microangiopathy) and diabetic patients before development vascular
      complications, suggesting the presence of an increased inflammatory response in
      these individuals.

PMID- 16617733
TI  - [CD40L expression on T CD4+ lymphocytes from peripheral blood in patients with
      relapsing-remitting and secondary progressive multiple sclerosis].
AB  - Multiple sclerosis (MS) is believed to be a T cell-mediated autoimmune disease.
      One of the particularly important signals is mediated by CD40L, a costimulatory
      molecule which appears on activated T cell. The aim of this study was examination
      of the CD40L expression on freshly obtained lymphocytes T CD4+ which were ex vivo
      stimulated with monoclonal antibody anti CD3+rIL-2 in patients with relapsing
      remitting and secondary progressive multiple sclerosis. MATERIAL AND METHODS: 12
      relapsing-remitting (RR) and 16 secondary progressive (SP) MS patients with long
      lasting clinical remission and 24 healthy subjects were included in the study.
      The proportion of unstimulated and ex vivo stimulated with anti CD3+rIL-2 TCD4+
      cells from peripheral blood co-expressing CD40L was studied by dual
      immunofluorescence method. RESULTS: The proportion of unstimulated and stimulated
      T CD4+CD40L+ cells did not differ significantly between RRMS and controls. The
      percentage of unstimulated TCD4+CD40L+ cells from SP patients exhibited
      significantly higher proportion - when compared with controls. These cells did
      not respond to ex vivo stimulation and their level was similar to that of
      stimulated cells from controls. CONCLUSION: Dysregulation of costimulation in
      SPMS expressing as enhanced percentage of TCD4+CD40L+ cells may be responsible
      for maintenance of chronic activation state of lymphocytes leading to prolonged
      inflammatory process.

PMID- 16617734
TI  - [Evaluation of soluble platelet cell adhesion molecule sPECAM-1 and chemokine MCP
      1 (CCL2) concentration in CSF of patients with tick-borne encephalitis].
AB  - Platelet-endothelial cell adhesion molecule-1 (PECAM-1) is a glycoprotein
      involved in the transendothelial migration of leukocytes and MCP-1 is a
      proinflammatory protein, member of the 1 subfamily of chemokines, acting as
      activator of specific leukocytes. The expression of PECAM-1 and MCP-1 was studied
      in various pathological processes, but very little is known about the
      significance of these molecules during inflammatory reaction in viral diseases of
      the nervous system, including tick-borne encephalitis. MATERIAL AND METHODS:
      Cerebrospinal fluid was obtained from 17 patients with TBE, treated at the
      Department of Infection Diseases in Bialystok. The level of sPECAM-1 and MCP-1
      was evaluated by the ELISA method. The control group consisted of 18 patients in
      which the battery of tests, including CSF study, has excluded the organic
      character of the neurological syndrome. The U- Mann-Whitney test was applied to
      establish the statistical significance of the results. RESULTS: The concentration
      of sPECAM-l and MCP-1 in cerebrospinal fluid of TBE patients was significantly
      increased in comparison with the. control group. CONCLUSIONS: Elevated
      concentration of sPECAM-1 and MCP-1 may be a result of increased release from
      endothelical cells, activated T-cells, platelets and monocytes. Increased
      expression of sPECAM-1 is the significant but unspecific event in immunological
      processes in inflammatory reaction in TBE. The increased concentration of MCP-1
      seems to be an essential event in the pathomechanism of inflammation in the
      central nervous system in TBE. It would be valuable in clinical conditions to
      search for the methods of inhibition of the increased expression of sPECAM-1 and
      MCP-1 in TBE to diminish the inflammatory reaction.

PMID- 16617735
TI  - [Concentrations of soluble factors participating in regulation of apoptosis of
      lymphocyte from patients with chronic lyme arthritis (preliminary report)].
AB  - Lyme borreliosis is a chronic infectious disease caused by Borrelia burgdorferi
      spirochete. The excess and inadequate inflammatory response and even autoimmunity
      is considered to participate in its pathogenesis. Apoptosis (programmed cell
      death) of activated lymphocytes contributes to regulation of immunological
      response and terminating the inflammation. AIM OF THE STUDY: To evaluate
      concentrations of soluble factors participating in regulation of apoptosis in the
      supernatants of the peripheral blood mononuclear cells (PBMC) of patients with
      chronic Lyme borreliosis. MATERIAL AND METHODS: The study group consisted of 10
      patients with chronic Lyme arthritis and the control group of 5 persons in whom
      Lyme borreliosis was excluded. In the supernatant of PBMC culture incubated with
      Borrelia burgdorferi antigens concentrations of potentially anti-apoptotic
      factors: soluble receptor for tumor necrosis factor alpha (sTNF-RI), soluble Fas
      (sFas) and soluble Fas ligand (sFasL), as well as the concentration of
      transforming growth factor beta (TGF-beta), cytokine synthesized in the final
      stage of apoptosis, were measured by ELISA. RESULTS: Concentrations of sTNF-RI,
      sFas and sFasL, but also TGF-beta tended to be increased in the study group in
      comparison with nonstimulated PBMC and the control group. CONCLUSIONS: These
      data, although they should be considered preliminary because of the small size of
      the groups, suggest possible impairment of the apoptosis of lymphocytes in the
      chronic Lyme borreliosis.

PMID- 16617736
TI  - [Beta-Thalassemia in Poland. I. Mediterranean mutations in beta-thalassemia].
AB  - The aim of the present investigation was to verify a common view that thalassemia
      in Poland is a very rare disease. MATERIAL AND METHODS: 600 patients (270 male
      and 330 female) aged 2-85 years with microcytosis and no evidence of iron
      deficiency were examined for beta-thalassemia. Hemoglobin A2 and hemoglobin F and
      bilirubin were evaluated. Patients with elevated A2 hemoglobin concentration were
      examined for 8 common Mediterranean mutations. RESULTS: Hemoglobin A2 was
      increased in 106 patients. In 48 patients there was also an elevation of
      hemoglobin F and in 42 - of serum bilirubin. 7 different mutations were detected
      in 46 heterozygous patients (numbers of patients with a particular mutation are
      in square brackPis): IVS1-6(T>C) [15], IVS2-745(C>G) [14], IVS2-1(G>A) [10], IVS1
      1(G>A) [2], CD6-A [2], CD39(C>T) [2], IVS1-110(G>A) [1]. CONCLUSIONS: Frequencies
      of individual mutations in Poland were different from those encountered in
      Mediterranean and some Central European countries. Our data indicate that fl
      thalassemia in Poland is not a rare disease and should be considered in
      differential diagnosis of hypochromic anemia.

PMID- 16617737
TI  - [The influence of Q10 coenzyme on structural and functional parameters of red
      blood cells in elderly people].
AB  - The free radical theory of aging assumes that aging process leads to lost of
      oxidative balance. Oxidative stress induces structural and functional changes in
      red blood cell. The Q10 coenzyme is known as a compound which may partially
      prevent those changes in erythrocytes, due to its antioxidative properties and
      the important role it plays in the cell. The content of the coenzyme in human
      body decreases with age. The aim of the research was to evaluate the degree of
      membrane lipid peroxidation, internal microviscosity, activity of membrane ATP
      ase and oxidative damage markers of erythrocyte membrane protein in elderly
      people before and after Q10 coenzyme therapy. MATERIAL AND METHODS: The
      examination was performed on 35 people. The examined group consisted of elderly
      people (older than 65 years old). The reference group was formed with people at
      the age between 51 and 59. In both groups the initial parameters of red blood
      cells were evaluated. In the elderly people the investigated parameters were also
      controlled after three and six weeks of Q10 coenzyme intake. RESULTS: The Q10
      coenzyme supplementation in elderly people produced the increase in the -SH group
      contents and reduction of W/S parameter. After supplementation of Q 10 coenzyme
      the decrease of lipid peroxidation products and internal microviscosity of
      erythrocytes and increase of the activity of membrane ATP-ase (total and Na+,K+)
      were observed. CONCLUSION: The obtained results may indicate the intensification
      of oxidative stress in elderly and point to beneficial effect of supplementation
      metabolic therapy with Q10 coenzyme on structural and functional parameters of
      red blood cells in elderly people.

PMID- 16617738
TI  - [Does the hearing loss affect the child's innate immunity?--preliminary].
AB  - Human neutrophiles play a crucial role in inmate immunity. Inmate and aquired
      immune response depend on their functional condition at the first stage of an
      inflammation process. Reactive forms of oxygen (RFO) produced by neutrophiles
      play a significant role in the eradication of pathogens as well as in the
      regulation of immune response. The aim of this study is question, does the
      hearing loss affect the inmate immunity? METHOD: The RFO production was directly
      examined in four systems - without stimulation, after stimulation with fMLP,
      opsonized zymosan or PMA. Direct RFO measurement was performed chemiluminescency
      evaluation using the whole blood, which indirectly depend on RFO production.
      RESULT: In the group of children with hearing loss was observed disturbances in
      RFO productions. CONCLUSION: This observation is very original and important for
      general practice.

PMID- 16617739
TI  - [Effect of methylprednisolone on the attention in patients with multiple
      sclerosis].
AB  - The aim of the study was to examine effects of high doses of intravenous
      methylprednisolone (MP, 1 g daily, for 5 days) on the sustained attention and
      attention focusing in multiple sclerosis (MS) patients with clinical relapse.
      MATERIAL AND METHODS: Thirty four relapsing-remitting patients were included. The
      mean age was 39.4 (20-56) years, mean disease duration and mean Expanded
      Disability Status Scale scores were 6.6 (0.8-18) years and 4.1 (2.0-6.0),
      respectively. MS patients underwent psychological testing three times: before and
      immediately after MP treatment, and 6 months later. The trials: "100-7" and
      "months of year backwards", The Brickenkamp d2 test, and The Visual Continuous
      Attention Test (DAUF) were used. Thirty two control subjects (mean age 37.2
      years) with ischialgia, not receiving steroids, underwent the same testing
      procedure two times: at admission and on 6th day of hospitalization. RESULTS:
      Before and immediately after MP treatment MS patient obtained significantly worse
      scores than controls on the DAUF test (significantly decreased number of correct
      reactions (p<0.05), significantly increased number of incorrect reactions
      (p<0.05), and significantly increased mean value of reaction times (p<0.05)).
      There were no significant differences within MS and control subjects on other
      tests. Therapy with MP did not markedly change an ability to focus attention and
      keep the concentration over long period of time in MS patients. CONCLUSIONS: MS
      subjects show disturbances in the sustained attention. Therapy with MP does not
      significantly change the sustained attention and attention focusing in MS
      patients.

PMID- 16617740
TI  - [Detection of patients at risk for paroxysmal atrial fibrillation (PAF) by signal
      averaged P wave, standard ECG and echocardiography].
AB  - The aim of this study was to evaluate whether analysis of signal averaged P wave,
      together with left atrial diameter (LA) and P wave duration in surface ECG lead
      II (PII) allow to predict the risk of PAF. MATERIAL AND METHODS: Patients with
      coronary heart disease and/or hypertension were examined (n=145). They were
      divided into two groups 110 patients with PAF were compared with 35 patients
      without PAF Age (60,5 vs. 57,4 years) and LA size (39,8 vs. 3,7 mm) were similar
      in two groups. RESULTS: The root mean square voltage (RMS) for the last 10,20, 30
      ms were calculated and for all of the filtered P wave (RMSW) were measured RMS
      ratio (RMSR) were calculated according to RMSW/ RMS20. Filtered P wave duration
      (PWD) and difference befteen PWD and P II (PWD-PII) were established. Most of the
      analyzed parameters were statistically significant (p<0,05). The statistical
      analyses made it possible to outline the score index evaluating how PAF reacts
      parameters. CONCLUSIONS: Score index evaluating of the PAF occurrence and its
      influence is statistically significant with sensitivity 86%, specificity 83,5%
      and index positive predictor 82,7% and index negative predictor 83,7%. The most
      significant parameters which detect the patients with the occurrence of PAF are
      PWD > or =130ms, RMS20<3, microV, RMS10<2,2 microV and PWD-PII > or =40 ms.

PMID- 16617741
TI  - [Primary tracheobronchial amyloidosis].
AB  - The primary tracheo-bronchial amyloidosis is a rare entity with long lasting and
      progressive course. Precise diagnosis can be established on the basis of
      pathological features seen in samples derived from the airways, obtained during
      fibreoptic bronchoscopy or during lung biopsy sometimes. Describing the case of
      an insidious course of primary tracheobronchial AL type amyloidoisis, that was
      initially recognised and treated as a chronic obstructive pulmonary disease. The
      authors represent its clinical course and the diagnostic difficulties. The
      changes in the respiratory tract, both radiological and endoscopic suggested a
      tuberculous or proliferative process. They were responsible for a severe
      increasing dyspnoea, due to bronchial obstruction, with muco-haemoptic
      expectoration. A forceps resection of the endobronchial lesions enabled to
      established the right diagnosis and further treatment limited to local
      procedures.

PMID- 16617742
TI  - [Usefullness of scintigraphy with somatostatin analogues in the imaging of
      insulinoma of the pancreas].
AB  - We present a case of a 74-years-old female with insulinoma of the pancreas.
      Neuroglycopenic symptoms (Whipple's triad) and a positive fast test established
      the diagnosis. The fast was terminated after 5 hours and 40 minutes because of
      neuroglycopenic symptoms with the serum glucose and insulin levels of 40 mg/dl
      and 34,01 microU/ml respectively. The tumor was invisible in ultrasound,
      abdominal CT scan and MRL The only means that enabled preoperative visualization
      was 111-Indium labeled octreotide scintigraphy (OctreoScan). Laparotomy was
      performed, and a tumor was disclosed in intraoperative ultrasonography within the
      head of the pancreas. The tumor of 37 mm diameter was excised. Histopatological
      examination revealed benign insulinoma. After surgery the symptoms alleviated
      completely. The patient with proper glucose levels and insulin concentration of
      3,04 microU/ml was discharged in good health. This case confirms high usefulness
      of preoperative OctreoScan and intraoperative ultrasonography in the approach to
      a patient with insulinoma.

PMID- 16617743
TI  - [Congenital renal arteriovenous fistulas--report of two cases treated by
      embolisation and nephrectomy].
AB  - Congenital arteriovenous fistulas of the kidney are very rare. Options for
      therapy range from embolisation to nephrectomy. It depends on symptoms and
      extensiveness of the malformations. We report two cases of congenital
      arteriovenous malformations successfully managed in the first case by
      embolisation and in the second case by nephrectomy. Renal arteriovenous
      malformations remain an uncommon clinical problem which causes often diagnostic
      difficulties. The proper diagnosis can be made on the basis of standard
      diagnostic procedures such as physical examination, Doppler sonography and spiral
      computerized tomography.

PMID- 16617744
TI  - [The pathogens of atypical respiratory infections and asthma].
AB  - The pathogens of atypical respiratory infections form a big heterogeneous group
      of different microorganisms. The classical ones belong to bacterial species of
      Mycoplasma pneumonaie, Chlamydia pneumoniae and Legionella pneumophila. This
      category comprises also some viruses and rickettsia. In many cases they are
      responsible for the asthma course exacerbation. Their contribution in the asthma
      development is suspected, too. Potential protecting effect against atopy and
      asthma is a subject of speculations. The authors discuss all three aspects,
      reporting own observations. A precise determination of the role of atypical
      infection in asthma remains to be determined.

PMID- 16617745
TI  - [Endovascular management of abdominal aortic aneurysm].
AB  - Not all patients with abdominal aortic aneurysm (AAA) are candidates for
      endovascular aneurysm repair (EVAR), but as further technologic refinements
      occur, it is likely that an increasing percentage of patients will be candidates.
      EVAR, pioneered by Parodi in early 1990s, has made significant progress in all
      aspects. In the early stages of development, stent grafts were used only to
      repair abdominal aortic aneurysms (AAAs) in patients with comorbidities (e.g.
      chronic obstructive pulmonary disease or myocardial infarction) significant
      enough to preclude open repair. With the advent of new technology, the rapid
      spread of the skill sets needed to place these grafts, and the demonstration that
      these grafts are not only safe but also durable, EVAR is now being used more
      commonly in patients who would otherwise undergo open repair. Nevertheless, EVAR
      is still in the early stages of development, and long-term follow-up of EVAR
      patients is essential to assure durable protection from AAA rupture. The authors
      present the review of epidemiology and possibilities of endovascular management
      of abdominal aortic aneurysm.

PMID- 16617746
TI  - [Proinflammatory cytokines in pathogenesis of periodontal disease].
AB  - The pathologic mechanisms of periodontal disease are still not completely
      understood. Current knowledge concerning the pathogenesis of periodontitis
      suggests an interaction between putative periodontal pathogens and the host
      defense system which results in the inflammation and eventual destruction of
      supporting periodontal tissues, including connective tissue and alveolar bone.
      Bacterial products stimulating host cells lead to a release of inflammatory
      mediators such as cytokines. These regulators have attracted particular research
      attention and are suspected to be involved in both inflammation-related
      alteration and repair of the periodontal tissues. This study - based on current
      literature - shows the modern understanding of the role of proinflammatory
      cytokines in periodontal disease pathogenesis.

PMID- 16617747
TI  - [Airway remodeling in asthma].
AB  - Asthma is a chronic inflammatory disease of the airways. Structural alteration of
      the airways and lung parenchyma, "remodeling", is a recognized feature of chronic
      asthma and a cause of irreversible airway obstruction. Airway and lung remodeling
      in asthma involves subepithelial fibrosis, but also alterations of bronchial
      epithelium, airway smooth muscle cells, myofibroblasts, extracellular matrix,
      mucous glands, blood vessels and nerves. Defining of morphological changes and
      correlating them with clinical features of the disease has been a major focus of
      research over the past decade. The results of these studies are often
      contradictory and there is still little understanding of the mechanisms
      underlying lung remodeling in asthma.

PMID- 16617748
TI  - [Gastroesophageal reflux disease and coronary heart disease--coexistence or
      interrelationship?].
AB  - There is the normal coronary artery appearance in 20-30% of coronarographies,
      made in patients with chest pain and/or positive noninvasive cardiological tests.
      The simple explanation of this fact is the presence of diseases which may affect
      coronary perfusion via mechanism independent to the diameter of main coronary
      arteries. One of them is gastroesophageal reflux disease (GERD). The presence of
      GERD symptoms in general population concerns about 30-40% of individuals, while
      non-physiological reflux is stated in 50-65-85% of patients with coronary heart
      disease (CHD). That means, that GERD is twice more frequent in patients with CHD
      than in general population. One explanation of the increased frequency of
      gastroesophageal reflux appearance in patients with CHD is the adverse effect of
      drugs used in treatment of cardiological diseases. Morover, one of potential
      mechanisms explaining the influence of esophagal disturbance on the appearance of
      coronary hipoperfusion may be their common neurological control of the functions.
      There are three aspects of it: vagal reflexes (esophageal-cardiac reflex), the
      disturbances of autonomic nervous system balance and changes in visceral pain
      perception threshold. Visceral reflex can combine GERD and CHD with mechanism of
      vicious circle: acid gastroesophageal reflux via vagal reflex may cause coronary
      hipoperfusion, and the products of anaerobic metabolism of cardiomyocytes may
      cause relaxation of lower esophagus sphincter, facilitating reflux. Additional
      mechanism connecting GERD and CHD is inflammation caused by Helicobacter pylori
      infection. The relationship between digestive tract pathology and evolution, as
      well as progression and complications of atherosclerosis together with similarity
      of clinical presentation imply the necessity of precise diagnosis of chest pain
      causes and caution in interpretation of laboratory examination results.

PMID- 16617749
TI  - [Respiratory tract amyloidosis].
AB  - Amyloidosis is a group of biochemical disturbances, leading to extracellular
      deposition of misfolded protein fibril's. It can be of primary, secondary or
      hereditary (familial) origin. The disorder is known from 150 years, and as
      already 23 fibril precursor proteins have been identified. Its symptoms can be
      systemic, localized; some forms don't produce any clinical manifestation. In this
      article amyloidosis pathogenesis, classification, epidemiology, prognosis and
      clinical characteristics are described, mainly with reference to the respiratory
      system.

PMID- 16617750
TI  - [Molecular mechanism of hereditary spherocytosis].
AB  - Hereditary spherocytosis (HS) is a common inherited anaemia in northern Europe
      characterized by the presence of spherocytic red cells and by heterogeneous
      clinical presentation, and heterogeneous molecular basis and inheritance. The
      primary molecular defects reside in the red blood cell membrane, particularly in
      proteins involved in the vertical interactions between the membrane skeleton and
      the lipid bilayer. Defects in these interactions lead to the loss of red cell
      surface area and to the spheroidal shape of the erythrocyte in particular loss of
      the membrane elasticity and mechanical stability. Severe HS is often associated
      with a substantial reduction of, and (or) dysfunction of, the affected membrane
      protein(s). Hereditary spherocytosis stems from mutations in one of the genes
      encoding ankyrin-1 (ANKI), alpha spectrin (SPTA1) and beta spectrin (SPTB), the
      anion exchanger 1 (SLC4A 1), and protein 4.2 (EPB42). Inheritance of HS is
      usually (75%) autosomal, dominant. Recessive and nondominant cases are mostly
      found in HS associated with ANK1, SPTA1 and SPTB genes.

PMID- 16617751
TI  - [Genetics in systemic sclerosis].
AB  - Systemic sclerosis (SSc) is chronic autoimmune disease that may affect many
      organs. Genetic and environmental factors are implicated in the pathogenesis of
      SSc. Systemic sclerosis prevalence is connected with sex, autoimmune diseases or
      phenomena, several ethnic groups and families. In this study we describe numerous
      genetic phenomena that may be implicated in the etiopathogenesis of SSc. i.e.
      antigens of major histocompatibility complex, microchimerism, polymorphism of
      several genes coding extracellular matrix components, receptors, adhesion
      molecules and cytokines. Genetic background plays an important role in this
      disorder and is connected with multiple genes.

PMID- 16617752
TI  - [Modern management of dandruff].
AB  - Dandruff is a common complaint and is suffered by as many as 50% of the
      population at some time during their life and cause significant discomfort. The
      condition is generally characterized by the presence of flakes on the scalp and
      in the hair, and by itch. The symptoms can vary, and the severity can range from
      mild scaling, similar to dry skin, to severe scaling. Its prevalence and severity
      is greatest in young men, with children and older individuals suffering less
      frequently. It is commonly aggravated by changes in humidity, trauma (e.g.,
      scratching), seasonal changes, and emotional stress. Dandruff responds to
      everyday shampooing and a longer period of lathering. Use of hair spray or hair
      pomades (gels) should be stopped. Salicylic acid, tar, selenium, sulfur, and zinc
      all are effective in shampoos and may be alternated. Overnight occlusion of
      salicylic or urea oil may help to soften thick, scalp plaques. The common
      causative agent is now accepted to be the lipohilic yeasts Malassezia spp.
      (previously Pityrosporum) which is increased in the scaly epidermis of both
      dandruff and seborrhoeic dermatitis sufferers. Selenium sulfide, imidazoles or
      ciclopirox olamine shampoos may help by reducing Malassezia scalp reservoirs. The
      wide range of antifungal shampoos available provides safe, effective and flexible
      treatment options for dandruff.

PMID- 16617753
TI  - [Pharmacoeconomics of dyspesia and peptic ulcer disease].
AB  - The economic impact of medical procedures in the treatment of some diseases is
      often conducted in USA and some EU countries. Recommendations of experts are
      different of diagnosis and treatment non ulcer disease (NUD) and peptic ulcer
      disease (PUD) with or without Helicobacter pylori (HP) infections. This study was
      to establish various methods of pharmakoekonomics analysis by NUD and PUD.

PMID- 16617754
TI  - 1656-2006: 350 years of intravenous injection.

PMID- 16617755
TI  - A survey of obstetric an aesthesia practice in Flanders.
AB  - The use of locoregional anaesthesia in obstetrics in Flanders was assessed by a
      postal questionnaire sent to the directors of the anaesthesia departments of the
      72 hospitals with an obstetric unit. 59 (82%) answers were returned. In the group
      of parturients who had a vaginal delivery a neuraxial technique was requested by
      65% of the patients and consisted of epidural analgesia in 84%, and combined
      spinal epidural analgesia in 16%. Test doses are used in labour in 67%. To
      perform the block--spinal as well as epidural--the sitting position is somewhat
      preferred over the left lateral (55 versus 45%). For caesarean section general
      anaesthesia was used in only 5% of the deliveries, whereas spinal, single or as a
      part of a CSE technique, was preferred in 80%; the epidural technique was applied
      in 15%. There is no clear preference in technique for postoperative analgesia
      after caesarean delivery as both parenteral and epidural analgesia are used in
      50% of the cases.

PMID- 16617756
TI  - Low-dose combined spinal-epidural anesthesia for cesarean delivery: a comparison
      of three plain local anesthetics.
AB  - The new local anesthetics have been poorly studied for intrathecal use during
      Cesarean section surely in low doses and in combination with an opioid substance.
      The purpose of the present study was to compare bupivacaine and the newer local
      anesthetics in equipotent doses. During the induction of combined spinal-epidural
      anesthesia, 91 elective Cesarean section patients were randomly assigned to
      receive a spinal injection of either 10 mg ropivacaine or 6.6 mg bupivacaine or
      levobupivacaine both combined with sufentanil 3.3 microg. After securing the
      epidural catheter patients were turned to the supine position respecting a 15
      degrees left lateral tilt. The three local anesthetics were compared with respect
      to sensory and motor block, the need for epidural supplementation, the severity
      of hypotension and neonatal outcome. More patients in bupivacaine had a Bromage-3
      motor block at incision. The ropivacaine group required additional local
      anesthetics by the epidural route in 23% of the cases versus 10% in the
      bupivacaine group and 9% with levobupivacaine. This caused the interval between
      the spinal injection and the end of surgery to be longer in the ropivacaine
      group. Hemodynamic values were comparable between the three groups although a
      trend towards better systolic blood pressures and a lower incidence of severe
      hypotension were noticed in favor of levobupivacaine. Apgar scores and umbilical
      pH values did not differ. When performing a low-dose combined spinal-epidural
      technique for Cesarean section, the present study confirms that the new local
      anesthetics can be used successfully, induce less motor block but that
      ropivacaine requires at least a 50% larger dose than bupivacaine or
      levobupivacaine.

PMID- 16617757
TI  - Ropivacaine versus bupivacaine 0.125% with fentanyl 1 microg/ml for epidural
      labour analgesia: is daily practice more important than pharmaceutical choice?
AB  - Ropivacaine might be superior to bupivcaine for epidural labour analgesia because
      it appears to induce less lower extremity motor blockade. The clinical relevance
      of this difference is not yet clear. METHODS: In a double-blind randomised trial
      bupivacaine and ropivacaine each at 0.125% with 1 microg/ml fentanyl were
      compared for epidural labour analgesia. This study was performed in two
      university hospitals. RESULTS: Sixty-three nulliparous women with singleton
      pregnancies at term were included. There were no differences between bupivacaine
      and ropivacaine as far as motor blockade, analgesic outcome, mode of delivery and
      neonatal outcome are concerned. However, the clinical management of epidural
      analgesia differed significantly between the two institutions involved.
      Parturients of one institution had their epidural catheter placed earlier, needed
      less top-up medication, and had more successful mobilisations, when compared to
      the other institution. CONCLUSIONS: Institutional clinical practice can be
      significantly different. Pharmacological differences between bupivacaine and
      ropivacaine at 0.125% with 1 microg/ml fentanyl seem to be less important than
      differences between institutions in terms of clinical practice.

PMID- 16617758
TI  - Identification of the epidural space: stop using the loss of resistance to air
      technique!

PMID- 16617759
TI  - The treatment and prevention of post-dural puncture headache.

PMID- 16617760
TI  - Drug mislabeling errors [corrected] in (obstetric) [corrected] anaesthesia.

PMID- 16617761
TI  - Non-programmed clamping of superior vena cava. The anesthesiologist's Achilles'
      heel.
AB  - This case presentation focuses on the hemodynamic alterations due to acute
      clamping of superior vena cava (SVC) during a right pneumonectomy for lung cancer
      and on the alternatives for drug administration. In a 71-yr-old female patient
      without clinical manifestations of SVC syndrome, this large vein was clamped for
      22 minutes for patch placement after sudden and unpredictable hemorrhage. The
      patient became acutely cyanotic and edematous in the face and upper extremities,
      arterial blood pressure dropped and the venous pressure in the right internal
      jugular vein was elevated. Drugs for managing the patient were given
      endobronchially and via an established right atrium line. Postoperatively, no
      neurologic deficit was noted. This case demonstrates the difficulties for
      managing patients without superior vena cava syndrome in which acute, non
      programmed intra-operative SVC clamping is performed, as this is followed by
      systemic and brain hemodynamic deteriorations that may lead to bad outcome.

PMID- 16617762
TI  - [Long term results after total hip replacement--cemented and cementless in young
      rheumatic patients].
AB  - T.H.R in young adults or in youth is still doubtful in the aspect of late results
      and inevitability of revisions. Rheumatic patients are a specific group due to
      character of the disease, multiorgan complications and side effects of
      pharmacological treatment. Aim of the study was to evaluate the late results and
      to compare cemented and cementless T.H.R. MATERIAL AND METHODS: between 1980-1990
      122 T.H.R (70 cementless and 52 cemented) on 80 rheumatic patients of age from 18
      do 42 (average 28.5) were performed in our clinic. The follow-up was from 14 to
      24 years. Clinical and radiographic examinations were done on 28 patients (35%)
      with 21 cementless and 21 cemented prostheses. 16 patients had bilateral T.H.R.,
      8 patients died. The results were evaluated using Merle d'Aubigne hip score and
      by own opinion of patients. There were 7 revisions due to aspetic loosening in
      cementless (in 2 cases only acetabular components) and 6 in cemented prostheses.
      There were no superficial or deep infections. Obtained results indicated that
      survivorship of prostheses was rather long. It was probably due to limited
      general mobility caused by pathologic changes in other joints of lower limbs and
      using aids during walking. The results after cemented and cementless prostheses
      were similar. Adjournment of operation in young rheumatoid patients is useless
      because in the later stage of the disease is more difficult.

PMID- 16617763
TI  - [Osteoarthritis secondary to the developmental hip dysplasia-treatment options in
      young patients].
AB  - The choice of the treatment method in young patients with osteoarthritis
      secondary to the developmental hip dyplasia is one of the most difficult dilemmas
      in orthopaedic practice. Currently total cementless hip replacement with metal-on
      metal articulation is a routine procedure. Young patients are particularly
      exposed to the risk of aseptic loosening due to their high activity and long
      duration of life with implant. Basing on our material, using selected clinical
      cases, options for treatment of OA secondary to DHD were presented. The paper
      presents the progress of OA seconary to DHD treated in childhood and its
      subsequent treatment using intertrochanteric osteotomy without changing the neck
      shaft angle, intertrochanteric osteotomy combined with shelf procedures, isolated
      shelf procedures and periacetabular osteotomies according to Ganz. Both
      satisfactory results with pain relief for any years so like negative ones with
      total lack of improvement were shown. Presented options for treatment alternative
      to THR may be helpful in determining the individual management in young adults.

PMID- 16617764
TI  - [Clinical signs and methods of treatment of enchondromas located outside the
      hand].
AB  - 160 patients (72 men and 88 women) in the age from 12 to 71 were admitted to
      Orthopaedic and Traumatology Department Skubiszewski Medical University in Lublin
      because of enchondromas. In 126 patients chondromas were located in hand, and in
      34 remaining patients (21,3%) in: humerus, forearm, femur, tibia, fibula and
      foot. The typical signs of enchondroma were: pain, little limitation of movement,
      thickening of tissues or pathological fracture. 31 patients were operated on.
      Enchondroma was resected with cutterage, the walls of osseus cavity cleaned with
      reamer and bone loss filled up with bone grafts or bone cement. 1 case of
      recurrence of chondroma of toe was noted. In one patent malignant change of
      chondroma of proximal metaphysis of tibia to chondrosarcoma was observed. Lesion
      resection and filling up the bone defect is the best method of treatment of
      enchondroma.

PMID- 16617765
TI  - [Carpal tunnel syndrome--assessment of nerve decompression with the "double
      approach" technique].
AB  - In the paper is presented the evaluation of the operative treatment of patients
      with carpal tunnel syndrome with minimally invasive procedure. Material includes
      33 patients (36 operated nerves) being operated form 2001 to 2004. The evaluation
      was proceeded before operation and in control examinations 4 week and 6 months
      after operation. In the evaluation both subjective and objective method of the
      outcome were utilized. At the final examination with the subjective-method all
      patients presented either very good or good outcome. In the objective evaluation
      in 30 cases (83.4%) the outcome was very good or good. In the rest six cases
      (16.6%) the outcome was satisfactory or poor. Minimally invasive methods in
      treatment of carpal tunnel syndrome allows the achievement of good results
      especially in subjective perspective relieving the symptoms.

PMID- 16617766
TI  - [Cubital tunnel syndrome: results of simple decompression].
AB  - 32 cases of cubital tunnel syndrome were treated by simple decompression of the
      ulnar nerve. Physical examination showed that ulnar nerve function - motor and
      sensory improved after surgery treatment. Simple decompression is a reliable and
      effective surgical option.

PMID- 16617767
TI  - [Assessment of radiological results of anterior cervical discectomy with
      different fusion cages].
AB  - The purpouse of this study was to compare results of anterior cervical
      decompression and fusion for cervical disc disease with 2 different interbody
      devices: titanium cylinder-design cage and carbon box-design cage. The results of
      operations of 46 patients (60 instrumented levels) divided in to groups according
      to implant type were examined to asses the restoration of disc height, clinical
      outcome, bony fusion and complication rate. In the cylinder-design cage group
      average postoperative restoration of disc height was 72% but with narrowing rate
      of 26% in follow up. In the carbon box group postoperative disc height
      restoration was 51% with narrowing in follow up to 6%. Clinical outcome was
      comparable in both groups and loss of disc height in cylinder-design cage group
      had no effect on clinical outcome. There were 2 cases of pseudoarthrosis in
      cylinder cage group. Overall the study shows better radiological outcome of
      carbon box-design cages in comparison to cylinder design cages with no influence
      on clinical effect.

PMID- 16617768
TI  - [The prevalence and character of neurologic deficit relating to clinical forms of
      cervical spondylosis].
AB  - The research was performed on 86 male patients between 41 and 83 years who were
      either hospitalised or treated in the out-patients clinic due to cervical
      spondylosis. The aim of the research was to evaluate the frequency and advance of
      neurologic, complications relating to the type and severity of lesions in
      cervical spine. The study showed significant relation between the degree of
      advance of cervical spondylosis and age, pain as well as prevalence and severity
      of neurologic deficit in the tested group. The authors have emphasized the need
      of precise evaluation and differentiation of presented forms of degenerative
      spine disease.

PMID- 16617769
TI  - [Quality of life and back pain].
AB  - Back pain considering generality of its occurrence became an epidemiological
      problem. In a significant part the pain is persistent and not corresponds on
      treatment. An aim of this study was to explore a connection between chronicity of
      pain and quality of a life. An instrument of study was a questionnaire consisting
      of 6 groups of questions relating to a character of pain, its origin, and its
      influence on work, social and family relation. Thirty people (21 women and 9 men)
      in the age of 49 and 46 years with chronic back pain took part in examination. In
      relations of patients an origin of pain is strongly connected with character of
      work and beside of this pain would have a negative influence on life-
      satisfaction and a results of work. Results confirm a significant influence of
      pain on a quality of people life in different fields and besides of this they
      connect chronicity of process and its character with personal, psychological
      profile of participants.

PMID- 16617771
TI  - [Post-traumatic aneurysm of the ulnar artery--a report of 2 cases].
AB  - Two cases of post-traumatic aneurysms of the ulnar artery within the hand in
      patients aged 28 and 45 years are presented. First one developed following blunt
      trauma of the hypohtenar during use of the screwdriver, other one was caused by
      puncture, penetrated injury. Both were typically localised at the base of the
      hypothenar and both were asymptomacic. Presence of the pulsating tumour in the
      palm was a cause of the medical appointment. Arteriography was performed in both
      cases that confirmed diagnosis of the aneurysm. Patients were operated on 2
      months after initial injury. The aneurysm was resected and ulnar artery was re
      anastomosed by vein graft in one case, and by direct suture in the other one.
      Anticoagulants were administered post-operatively. In both cases the course was
      uneventful, and phone call one year after operation revealed only some symptoms
      of cold intolerance in one patient. The likelihood of aneurysm formation as a
      consequence of blunt and sharp trauma of the hand was suggested as well as the
      necessity of prompt diagnosis and operative treatment.

PMID- 16617770
TI  - [Value of collagen scaffolds in surgical reconstruction of articular cartilage].
AB  - Articular cartilage has a very limited capacity for regeneration and the
      untreated injuries of this tissue may lead to osteoarthritis. The aim of this
      study was to evaluate the application of collagen scaffolds in surgical
      reconstruction of articular cartilage. A group of 28 rabbits was used in the
      study. A defect penetrating into the subchondral bone was made. The animals were
      divided into 2 groups: group 1- defects filled with collagen scaffold, group II
      the defects remained empty. The results were evaluated at 4 a 12 weeks.
      Macroscopic and microscopic evaluation was performed. On gross examination of the
      group I complete filling of the defect with regenerated tissue was observed. This
      tissue had smooth surface and was completely integrated with the surrounding
      cartilage. In the group II the surface of the newly formed tissue showed large
      irregularities. The defect was partially filled and incompletely integrated with
      the residual cartilage. Microscopic results indicate presence of hyaline-like
      cartilage resembling normal articular cartilage in group I. Regenerate was more
      stable and remained stable with longer follow-up. Group II revealed mostly
      fibrous tissue in regenerate. Thickness was inadequate with visible surface
      irregularities and loss in tissue integrity. This study proved better results of
      reconstruction of articular cartilage by means of biodegradable scaffold.

PMID- 16617772
TI  - [Dislocation-disassembly of bipolar hip arthroplasty--case report].
AB  - Bipolar hip arthroplasty dislocation is rare. A case of bipolar hip arthroplasty
      dislocation in patient treated because of femoral neck fracture was described.
      Patient had neurological problems. The arthroplasty was made with posterolateral
      approach. Disassembly of bipolar prosthesis occurred during closed reduction.
      Open reduction with bipolar head exchange was necessary. To avoid this
      complication reduction should be made in anesthesia with muscles relaxation.

PMID- 16617773
TI  - [Isolation and fermentation culture of fungi from Cordyceps soofifera].
AB  - OBJECTIVE: To study the fungi isolated from Cordyceps sobolifera and its
      fermentation culture. METHODS: The fungi was isolated and identified by its hypha
      and spores. Three liquid media were used in the culture. RESULTS: Pure culture
      was gained and the fungi was identified to be Paecilomyces cicadae. The fungi can
      grow best in liquid media: egg 110 g + silkworm powder 30 g + VB1 2 tahlets +
      MgSO4 x 7H2O 0.5 g + K2HPO4 1 g + H2O 1000 ml, in which every litre can produce
      135 g wet hypha after cultured 4 d. CONCLUSION: Paecilomyces cicadae from
      Cordyceps sobolifera can be cultured in liquid media.

PMID- 16617774
TI  - [Growth comparison among Psammosilene tunicoides populations in tissue culture].
AB  - The comparison between the growth of eight populations from Psammosilene
      tunicoides at Yunnan Province was made by the tissue culture. The initial results
      showed out two populations from Yunshanping (Lijiang) and Xiaomoyu (Kunming) was
      dominant than orthers. It would be regard as one of fine germplasm resources for
      the culture of Psammosilence tunicoides.

PMID- 16617775
TI  - [Infrared spectroscopy technology, one of the faster and more convenient methods
      to detect the stability of stored Niuxi].
AB  - OBJECTIVE: To detect the change of Niuxi in reserve and establish one easier
      method of evaluating the quality change of Niuxi. METHODS: Infrared spectroscopy
      and compare software were used to distinguish the different Niuxi, and simulation
      testing were used to observe calefactive stability. RESULTS: There were obvious
      difference between transmutative and normal Niuxi, and Niuxi had evident change
      when the temperature above 140 degrees C in the simulation testing. CONCLUSION:
      Infrared spectroscopy can be used to evaluae the quality stability of Niuxi. It
      is one tried method to provide the establishment of reserve and torrefaction
      conditions.

PMID- 16617776
TI  - [Pharmacognostical identification of Vernonia patula (Dry) Merr].
AB  - OBJECTIVE: To identify Vernonia patula (Dry) Merry. METHODS: Characteristic
      study, microscopic identification and UV spectrometry method were carried out.
      RESULTS: Obvious characteristics were found in the tissue structures of the
      roots, stems and leaves. CONCLUSION: The results can be taken as the reference
      for analyzing the quality of the crude drug.

PMID- 16617777
TI  - [Studies on fingerprints of Bupleurum chinense from Hebei Province with HPLC-UV].
AB  - OBJECTIVE: To establish a HPLC fingerprint analysis method for identification of
      Bupleurum chinense of Hebei Province and compare the fingerprints of Radix
      Bupleuri collected from different habitats so as to establish a sensitive and
      specific method for controlling the quality of Radix Bupleuri. METHODS: The HPLC
      UV fingerprints of Radix Bupleuri from different habitats were obtained from
      Waters 1525 instruments. The HPLC separation was performed on a C18 analytical
      column gradient eluted with a mixture consisting of acetonitrile and water at a
      flow rate of 1.0 ml/min with UV detector at 203 nm. The temperature of column was
      30 degrees C. RESULTS: The mutual mode of HPLC-UV fingerprints was set up, and
      the similar degrees to the crude drugs of different habitats were compared.
      CONCLUSION: It is simple and quick to differ Bupleurum chinense from different
      habitats with the method that can be used as a quality control item for Radix
      Bupleuri.

PMID- 16617778
TI  - [Identification on Spora Lygodii by X-ray diffraction fingerprint spectra
      method].
AB  - OBJECTIVE: To set up a new identification and analysis method of Spora Lygodii.
      METHOD: To get the extracts of Spora Lygodii using methanol, chloroform and
      petroleum ether as solvent and the extracts were identified, analyzed by X-ray
      diffraction Fourier fingerprint spectra. RESULTS: Experiments and analysis were
      carried out on three samples. The standard X-ray diffraction Fourier fingerprint
      spectra and characteristic diffraction peaks were obtained. There were some
      differences among the spectra of the extracts, but the characteristic diffraction
      peaks were obvious. CONCLUSION: The experimental result indicated that X-ray
      diffraction Fourier fingerprint spectra can be used to identify and analyze the
      Chinese traditional herb Lygodium japonicum (Thunb.) Sw.

PMID- 16617779
TI  - [Studies on the chemical constituents of Lagotis yunnanensis (II)].
AB  - OBJECTIVE: To study the chemical constituents of Lagotis yunnanensis W. W. Smith.
      METHODS: Compounds were isolated from the ethanolic extract of the title herb by
      silica gel column chromatography, and their structures were identified by
      physical and chemical evidences and spectral methods. RESULTS: Seven compounds
      were isolated and identified as artselaeroside A (1),3-hydroxy-5-methoxy-benzyl
      alcohol (2), tyrosol (3), glycerin-9'-Z-octadecaenate (4), glycerin-docosanate
      (5), glycerin-tetracosanate (6), tetracosanoic acid (7), respectively.
      CONCLUSION: All the compounds were isolated from this plant for the first time.

PMID- 16617780
TI  - [Studies on the chemical constituents from Asarum Chinese Franch. f. fargesii
      (Franch.) C. Y. Cheng (II)].
AB  - Three compounds were isolated from the roots and stems of Asarum chinese Franch.
      f. fargesii (Franch.) C. Y. Cheng with column chromatography methods. Their
      structures were identified as kakuol (I), 2-methoxy-4,5
      methylenedioxypropiophenone (II) and pluviatilol (III) on the basis of
      physicochemical and spectroscopic analysis. The compound II and III were isolated
      from the genus of Asarum for the first time.

PMID- 16617781
TI  - [Purification of a new phospholipase A2 homologue from Agkistrodon blomhoffii
      siniticus and its effects on gene expression of Hep3B cells].
AB  - A new PLA2 homologue was purified from Agkistrodon blomhoffii Siniticus by
      applying reverse phase (HPLC) C18 column. The molecular weight of PLA2 homologue
      is 13900Da and its purity is 97.2%. The results of N-terminal sequence analysis
      were HLLQFRKMIKKMTKK. All the fragments were determined with the protein-protein
      BLAST software of GenBank. BLAST analysis showed that the N-terminal sequences of
      15 amino acids were highly homologous with the sequences of other PLA2.

PMID- 16617782
TI  - [Extraction and salting-out purification of alpha-galactosidase and beta
      glucosidase from fresh roots of Rehmannia glutinosa].
AB  - OBJECTIVE: To extract and preliminarily purify alpha-galactosidase and beta
      glucosidase from the fresh roots of Rehmannia glutinosa. METHODS: With the enzyme
      activity as a criterion, the best procedure of extraction was selected though
      orthogonal design method, and the desired saturation of ammonium sulfate in two
      step salting-out was settled by gradient sedimentation of root extract according
      to enzyme activity and protein content. RESULTS: Temperature and solvent volume
      affect the extraction of alpha-galactosidase significantly, while solvent type to
      beta-glucosidase. Therefore the procedure for extracting two enzymes was decided
      as mixing comminuted fresh root with 3 times phosphate buffer, and placing the
      mixture in refrigeratory at 4 degrees C for 4 hours, and then obtaining the
      enzyme liquid by centrifuging at 4 degrees C. 30% and 60% saturation was defined
      as the lower and upper point for two-step ammonium sulfate salting-out of the two
      enzymes. CONCLUSION: alpha-Galactosidase and beta-glucosidase exist in the fresh
      roots, and can be preliminarily purified through two-step salting-out.

PMID- 16617783
TI  - [GC-MS analysis of volatile oil from the ear of Schizonepeta tenifolia Briq].
AB  - Volatile oil was extracted from the ear of Schizonepeta tenifollia Briq. by
      supercritical carbon dioxide extraction and steam distillation, then GC-MS was
      used to analyse their components and determine the content. There were 41
      components identified from products of supercritical carbon dioxide extraction,
      while 32 from those of steam distillation. The content of the main component,
      pulegone, was also different in the two extracts. It showed that the two
      extractions have differences in component and content to a certain extent.

PMID- 16617784
TI  - [Inhibitory effects of ampelopsin on angiogenesis].
AB  - OBJECTIVE: To study the effect of ampelopsin on angiogenesis. METHODS: The anti
      angiogenic effect was evaluated by MTT assay for proliferation of endothelial
      cells. The concentration of vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) from human hepatocellular carcinoma Bel-7402
      cells were detected by enzyme linked immunosorbant assay (ELISA).
      Immunohistochemical staining was conducted to detect the expression of VEGF and
      bFGF. The VEGF and bFGF in the cancer cells were examined by flow cytometry. The
      inhibitory effect of ampelopsin on the growth of human hepatocellular carcinoma
      Bel-7402 in nude mice was studied. RESULTS: Ampelopsin was shown to inhibit the
      proliferation of primary cultured bovine aortic endothelial cells in a
      concentration dependent manner in range of 6.4 - 51.2 microg/ml. The IC50 (50%
      inhibition concentration) value was 22.0 +/- 4.0 microg/ml. ELISA assay was shown
      that treatment with 12.8 microl/m1, 25.6 microl/ml and 38.4 microg/ml of
      ampelopsin resulted in an inhibition of VEGF production released by Bel-7402, and
      the inbibtitory rate was 14.2%, 40.0% and 49.6%, respectively. After exposure to
      12.8 microg/ml of ampelopsin, a decrease in the expression and activity of VEGF
      and bFGF was observed by immunohistochemical staining. The concentration of VEGF
      and bFGF secretion by Bel-7402 cells were lower following ampelopsin treatment as
      shown by flow cytometry. Treatment with 25.6 microg/mL and 38.4 microg/ml of
      ampelopsin, the inbibitory rates were 32.2% and 57.4% for VEGF, and 54.9% and
      62.6% for bFGF, respectively. The inhibitory rate of ampelopsin to the growth of
      the transplant tumor in nude mice were 24.3%, 41.4% and 45.75 respectively at the
      dose of 100 mg/kg, 150 mg/kg and 200 mg/kg. CONCLUSION: Ampelopsin is a potent
      inhibitor of VEGF and bFGF expression and production in human hepatocellular
      carcinoma Bel-7402 cell, and may be a promising angiogenesis inhibitor.

PMID- 16617785
TI  - [Study on the purification and scavenging free radical activity of water soluble
      polysaccharide of leave in Hippohae rhamnoides L].
AB  - The crude polysaccharide was extracted from Leave in Hippohae rhamnoides L. with
      hot water, and precipitated by ethanol. The crude polysaccharide has been
      fractionated by acidic ethanol. Three fractions (SJ1, SJ2, SJ3) were got
      respectively. SJ2 deproteinizationed by the combined methods of enzyme and
      Seveage, purified by DEAE-Sephadex A-25 gel filtration. PC analysis indicated
      that SJ22 is composed of Xyl,Ara,Glc,Gal,GaL A. The identification of purify by
      Sepharose CL-4B, paper chromatography and cellulous acetate electrophoresis
      showed it was homogeneous. Typical absorption of polysaccharides was shown in its
      IR spectrum. It contained a-glucosidic bonds by IR analysis. It had typical
      absorption of protein by UV scaning. SJ22 is first isolated from Leave in
      Hippohae rhamnoides L Scavenging free radical experiment showed that SJ22 was
      effective in scavenging superoxideradical and hydroxylradical, but only a little
      effective in scavenging lipid radical.

PMID- 16617786
TI  - [The fermentation of 50 kinds of TCMs by Bacillus subtilis and the assay of
      antibacterial activities of fermented products].
AB  - 50 Traditional Chinese medicines (TCMs) were fermented by Bacillus subtilis and
      the antimicrobial activities of the fermented products were assayed against
      Mycobacterium tuberculosis and Penicillium avellaneum. The results showed that
      some products of them had stronger antimicrobial activities, but some weaker than
      the corresponding raw materials, still some had no change, which indicated that
      microorganism and TCM can effect each other during fermentation.

PMID- 16617787
TI  - [Study on pharmacokinetics of PVP coated beta-elemene liposome in rats].
AB  - OBJECTIVE: To study the pharmacokinetics of PVP costed beta-elemente liposmes in
      rats. METHODS: Gas chromatography was established to determine the concentration
      of beta-elemene in plasma of rats after administered through i.g. RESULTS: The
      pharmacokinetics parameters was: T(1/2) = 95.07 +/- 20.46 min, AUC = 348.72 +/-
      32.49 microg x min/ml, Cmax = 4.39 +/- 0.33 microg/ml, Tmax = 60 min. CONCLUSION:
      The bioavailability of PVP coated beta-elemene liposomes is 140.2 +/- 7.5%
      compared with conventional liposomes.

PMID- 16617788
TI  - [Effect of Herba Lamiophlomis Rotata extract on rats blood conglomeration
      parameters by oral administration].
AB  - OBJECTIVE: To study the effect of Tibet medicine Herba Lamiophlomis Rotata exect
      (HLRE) on blood conglomeration parameters by oral administration. METHODS: High
      dose (3 g/kg), middle dose (1.5 g/kg) and low dose (0.75 g/kg) of HLRE had been
      given orally in rats for 7, 14, 21 days. Blood samples were collected from common
      carotid artery and prothrombin time (PT), activated partial thromboplastin time
      (APTT), thrombin time (TT), fibrinogen (FIB) were tested. RESULTS: After 7 days,
      as compared to the control, the high, middle doses of HLRE induced significant TT
      reduction, and all doses of HLRE could induce significant hyperfibrinogenemia.
      But there was no change in PT and APTL. After 14 days, in all groups treated with
      HLRE, TT decreased and FIB increased. As compared to the control, only the high
      dose had significantly changes in TT and FIB. After 21 days, as compared to the
      control, TT of high and middle groups decreased and FIB of high group increased
      visibly. PT decurtation could also be seen in all groups. There was a decrease in
      TT paralleling an increase of fibrinogen in our study. CONCLUSION: The aqueous
      extract of Herba Lamiophlomis Rotata orally administered in rats can increase the
      contents of FIB and shorten TT. The shorten of PT is found after treated with
      high dose for a long time. Hemostatic effect of HLRE has a dose-effect and time
      effect relationship.

PMID- 16617789
TI  - [Preparation and purification of polyclonal antibody against chymopapain].
AB  - OBJECTIVE: To prepare and purify polyclonal antibody against chymopapain, and to
      make a foundation for establishing an immunossay for chymopapain. METHODS: New
      Zealand rabbit was immunized with chymopapain. Antiserum was purified by Protein
      A and analyzed by ELISA. RESULTS: The titer of the antiserum obtained in this
      experiment by ELISA was up to 1:380000 and the purity was proved to be high by
      SDS-PAGE.

PMID- 16617790
TI  - [Study on the process of inclusion volatile oil of Herba Schizonepetae with beta
      cyclodextrin from xiao'er ganmaoshu granule].
AB  - OBJECTIVE: To study optimum inclusion process condition for volatile oil with
      beta-cyclodextrin (beta-CD). METHODS: The optimum preparation condition were
      investigated by orthogonal design. The influence of utilization beta-CD and oil,
      inclusion temperature and time were studied to determin the utilization ratio of
      volatile oil and oil-bearing rate. RESULTS: The optimum preparation conditions
      were established as: volatile oil: beta-CD was 1:10, the inclusion temperature
      was 60 degrees C and inclusion time was 3h. CONCLUSION: The method is convenient
      and can he used for mass production.

PMID- 16617791
TI  - The question of NEED: accepted versus optimal care.

PMID- 16617792
TI  - Oral cancer screening exam: case studies.

PMID- 16617793
TI  - Production, products, and your bottom line.

PMID- 16617794
TI  - Upgrading previously placed porcelain veneers: materials and technique.

PMID- 16617795
TI  - Oral hygiene and maintenance of dental implants.
AB  - When dental implants were first introduced, the emphasis for long-term success
      was on the surgical phase of treatment. Subsequently, the emphasis changed from a
      focus on the surgical technique to proper fixture placement, which would be
      dictated by the prosthetic and aesthetic needs of each patient. In more recent
      years, implant maintenance and effective patient home care have been emphasized
      as two critical factors needed for long-term success of dental implants.

PMID- 16617796
TI  - Maintaining crestal bone around dental implants: literature review and clinical
      technique.

PMID- 16617797
TI  - Principle-centered endodontics: Methods, strategies, and concepts.

PMID- 16617798
TI  - Gold foil and its use in modern dentistry.
AB  - Gold foil is the most underused restorative material in dentistry, and contrary
      to popular belief, it is still being used in many dental practices. As
      demonstrated, it can be used more easily than years ago and give the patient a
      restoration that may last a lifetime. Reasons for not using it have been
      addressed, and a simplified method of restoration has been explained in detail.
      It is the hope of the authors and the American Academy of Gold Foil Operators
      that this paper may stimulate some readers to investigate the use of gold foil as
      a restorative material. More information and educational opportunities may be
      obtained by contacting the authors or the Academy of Gold Foil Operators
      (goldfoil.org).

PMID- 16617799
TI  - Case presentation: full-mouth rehabilitation combining Captek and porcelain
      veneers.

PMID- 16617800
TI  - Efficient face-bow utilization: an essential step to predictable aesthetics.

PMID- 16617801
TI  - Tooth whitening: addressing the sensitivity problem.

PMID- 16617802
TI  - Oral manifestation of a food allergy: case report.

PMID- 16617803
TI  - Puppy dog sales, part 2: how to increase case acceptance with integrity and
      professionalism.

PMID- 16617804
TI  - Be careful what you ask for...you may just get it! Techniques for hiring
      effective staff.

PMID- 16617805
TI  - Harnessing the Internet: driving real business value through more effective
      patient communication.

PMID- 16617806
TI  - Digital radiology: innovation, not automation.

PMID- 16617808
TI  - Buyers' guide to impression materials.

PMID- 16617807
TI  - Buyers' guide to digital radiography--intraoral.

PMID- 16617809
TI  - Special deliveries.

PMID- 16617810
TI  - The toughest customers: how hardheaded business metrics can help the hard-core
      homeless.

PMID- 16617811
TI  - If you can't beat 'em... As more not-for-profit and for-profit hospitals consider
      joint ventures, navigating hidden benefits and pitfalls is key to success.
AB  - Joint ventures between not-for-profit and for-profit hospitals are becoming more
      popular. Denny Shelton, left, chairman and CEO of Triad Hospitals, says joint
      ventures offer Triad its greatest source of potential growth. Triad brings the
      capital and the not-for-profit brings the history and the brand name, he says.

PMID- 16617812
TI  - Coming clean. Legislative proposals seek pricing clarity for uninsured.

PMID- 16617813
TI  - N.Y. may limit charity to poor.

PMID- 16617814
TI  - Hitting where it hurts. Congress considers incentives, penalties to spur quality.

PMID- 16617815
TI  - Infection data bring bad news. Pa. attempt to report data shows worse problems.

PMID- 16617816
TI  - Construction with caution. Aging boomers might not justify expansion: study.

PMID- 16617817
TI  - New Orleans charity care soars. Huge decline in staffed beds adds to regional
      strain.

PMID- 16617818
TI  - Reimbursement with a catch.

PMID- 16617819
TI  - Specialty-hospital battle waged. Benefis leads legal charge against Mont.
      hospital.

PMID- 16617820
TI  - The baby-boom building bust? Report shows that predictions of a senior health
      spending spree may not pan out.

PMID- 16617821
TI  - Ten steps to reform. Getting escalating prices under control requires
      collaboration and goodwill.

PMID- 16617822
TI  - Cashing up, not out. Healthcare executives saw more compensation in 2004 despite
      the economy, according to Modern Healthcare's association salary report.

PMID- 16617823
TI  - By the numbers. Largest national healthcare associations. Organizations ranked by
      2004 revenue, with noted exceptions. Based on Modern Healthcare's review of IRS
      form 990 filings.

PMID- 16617824
TI  - Patients in motion. Network helps care for migrant workers.

PMID- 16617825
TI  - Segment duration as a cue to word boundaries in spoken-word recognition.
AB  - In two eye-tracking experiments, we examined the degree to which listeners use
      acoustic cues to word boundaries. Dutch participants listened to ambiguous
      sentences in which stop-initial words (e.g., pot, jar) were preceded by eens
      (once); the sentences could thus also refer to cluster-initial words (e.g., een
      spot, a spotlight). The participants made fewer fixations to target pictures
      (e.g., ajar) when the target and the preceding [s] were replaced by a recording
      of the cluster-initial word than when they were spliced from another token of the
      target-bearing sentence (Experiment 1). Although acoustic analyses revealed
      several differences between the two recordings, only [s] duration correlated with
      the participants' fixations (more target fixations for shorter [s]s). Thus, we
      found that listeners apparently do not use all available acoustic differences
      equally. In Experiment 2, the participants made more fixations to target pictures
      when the [s] was shortened than when it was lengthened. Utterance interpretation
      can therefore be influenced by individual segment duration alone.

PMID- 16617826
TI  - Grouping does not require attention.
AB  - Many theories of visual perception stipulate that Gestalt grouping occurs
      preattentively. Subjects' failure to report perceiving even salient grouping
      patterns under conditions of inattention challenges this assumption (see, e.g.,
      Mack, Tang, Tuma, Kahn, & Rock, 1992), but Moore and Egeth (1997) showed that
      although subjects are indeed unable to identify grouping patterns outside the
      focus of attention, effects of these patterns on visual perception can be
      observed when they are assessed using implicit, rather than explicit, measures.
      However, this finding, which is the only one to date demonstrating grouping
      effects without attention, is open to an alternative account. In the present
      study, we eliminated this confound and replicated Moore and Egeth's findings,
      using the Muller-Lyer illusion (Experiments 1 and 2). Moreover, we found
      converging evidence for these findings with a variant of the flanker task
      (Experiment 3), when the amount of available attentional resources was varied
      (Experiments 4 and 5). The results reinforce the idea that, although grouping
      outside the focus of attention cannot be the object of overt report, grouping
      processes can occur without attention.

PMID- 16617827
TI  - The aesthetic appeal of minimal structures: judging the attractiveness of
      solutions to traveling salesperson problems.
AB  - Ormerod and Chronicle (1999) reported that optimal solutions to traveling
      salesperson problems were judged to be aesthetically more pleasing than poorer
      solutions and that solutions with more convex hull nodes were rated as better
      figures. To test these conclusions, solution regularity and the number of
      potential intersections were held constant, whereas solution optimality, the
      number of internal nodes, and the number of nearest neighbors in each solution
      were varied factorially. The results did not support the view that the convex
      hull is an important determinant of figural attractiveness. Also, in contrast to
      the findings of Ormerod and Chronicle, there were consistent individual
      differences. Participants appeared to be divided as to whether the most
      attractive figure enclosed a given area within a perimeter of minimum or maximum
      length. It is concluded that future research in this area cannot afford to focus
      exclusively on group performance measures.

PMID- 16617828
TI  - Limits on integrating motion information across saccades.
AB  - In two experiments, we investigated whether people could detect changes in the
      rotary motion of a cube. A rendering of a cube rotating at a constant angular
      velocity was presented on a video monitor and, at a key point in the trial, a
      cross was presented to one side of the cube as a cue for a saccade. On some
      trials, a change in the rotation occurred either about 100 msec before the
      saccade or during the saccade; on other trials, there was no change. The change
      consisted of moving the cube to a new position in the "rotation sequence," after
      which it continued to rotate at the same angular velocity as before. There was
      also a control on all trials to ensure that change detection was not due to the
      detection of low-level motion. Although detection of the change was well above
      chance when it occurred during the fixation, it was at chance when it occurred
      during the saccade, except in the case of one participant (who was in both
      experiments). This chance performance also occurred in Experiment 2 for (1) a
      slower rotation speed and (2) an axis of rotation that made the rotation planar.
      The participant who had above chance performance (and as good as that when the
      change occurred during a fixation) reported using a "strategy" that did not track
      the path of the cube. It thus appears that there is no natural way in which the
      visualsystem tracks this rotary motion, and that detection of change requires
      some sort of recoding. This finding raises the question of whether good
      performance in other, apparently similar, motion-detection tasks is a result of
      similar recoding.

PMID- 16617829
TI  - Within-modality and cross-modality attentional blinks in a simple discrimination
      task.
AB  - Following up on studies of the "attentional blink," we studied interference
      between successive target stimuli in visual and auditory modalities. In each
      experiment, stimuli were two tones and four dots, simultaneously presented for
      1,800 msec. Targets were brief intensity changes in either a tone or a dot.
      Subjects gave unspeeded responses. In four experiments, our results showed
      interference between targets in the same modality, but not across modalities. We
      conclude that, under our experimental conditions, restrictions in concurrent
      target identification are largely modality specific.

PMID- 16617830
TI  - The structure of frontoparallel haptic space is task dependent.
AB  - In three experiments, we investigated the structure of frontoparallel haptic
      space. In the first experiment, we asked blindfolded participants to rotate a
      matching bar so that it felt parallel to the reference bar, the bars could be at
      various positions in the frontoparallel plane. Large systematic errors were
      observed, in which orientations that were perceived to be parallel were not
      physically parallel. In two subsequent experiments, we investigated the origin of
      these errors. In Experiment 2, we asked participants to verbally report the
      orientation of haptically presented bars. In this task, participants made errors
      that were considerably smaller than those made in Experiment 1. In Experiment 3,
      we asked participants to set bars in a verbally instructed orientation, and they
      also made errors significantly smaller than those observed in Experiment 1. The
      data suggest that the errors in the matching task originate from the transfer of
      the reference orientation to the matching-bar position.

PMID- 16617831
TI  - The proximity structure of achromatic surface colors and the impossibility of
      asymmetric lightness matching.
AB  - In asymmetric lightness matching tasks, observers sometimes report that they
      cannot achieve satisfactory matches between achromatic surfaces under different
      neutral illuminants. The surfaces appear different, yet no further adjustment of
      either surface improves the match. There are evident difficulties in interpreting
      data from a task that the observer cannot always do, and these difficulties
      likely affect the interpretation of a large number of previous studies. We
      investigated, as an alternative to asymmetric matching, the direct use of
      proximity judgments in the study of surface lightness perception. We asked
      observers to rate the perceived dissimilarity of pairs of achromatic surfaces
      that were placed in identical scenes and viewed under different neutral
      illuminants. We develop a parametric model that accurately predicts perceived
      dissimilarity in terms of physical light intensities and surface albedos. The
      parameters of this model are readily interpretable. In particular, the ratio of
      the influence of changes in illuminant intensity and changes in surface albedo is
      a measure of the extent to which the observer discounts the illuminant.
      Asymmetric lightness matching can be interpreted as an unachievable limiting case
      of proximity judgment.

PMID- 16617832
TI  - Hearing a face: cross-modal speaker matching using isolated visible speech.
AB  - An experiment was performed to test whether cross-modal speaker matches could be
      made using isolated visible speech movement information. Visible speech movements
      were isolated using a point-light technique. In five conditions, subjects were
      asked to match a voice to one of two (unimodal) speaking point-light faces on the
      basis of speaker identity. Two of these conditions were designed to maintain the
      idiosyncratic speech dynamics of the speakers, whereas three of the conditions
      deleted or distorted the dynamics in various ways. Some of these conditions also
      equated video frames across dynamically correct and distorted movements. The
      results revealed generally better matching performance in the conditions that
      maintained the correct speech dynamics than in those conditions that did not,
      despite containing exactly the same video frames. The results suggest that
      visible speech movements themselves can support cross-modal speaker matching.

PMID- 16617833
TI  - Aging and the perception of 3-D shape from dynamic patterns of binocular
      disparity.
AB  - In two experiments, we investigated the ability of younger and older observers to
      perceive and discriminate 3-D shape from static and dynamic patterns of binocular
      disparity. In both experiments, the younger observers' discrimination accuracies
      were 20% higher than those of the older observers. Despite this quantitative
      difference, in all other respects the older observers performed similarly to the
      younger observers. Both age groups were similarly affected by changes in the
      magnitude of binocular disparity, by reductions in binocular correspondence, and
      by increases in the speed of stereoscopic motion. In addition, observers in both
      age groups exhibited an advantage in performance for dynamic stereograms when the
      patterns of binocular disparity contained significant amounts of correspondence
      "noise." The process of aging does affect stereopsis, but the effects are
      quantitative rather than qualitative.

PMID- 16617834
TI  - Photometric, geometric, and perceptual factors in illumination-independent
      lightness constancy.
AB  - It has been shown that lightness constancy depends on the articulation of the
      visual field (Agostini & Galmonte, 1999). However, among researchers there is
      little agreement about the meaning of "articulation." Beyond the terminological
      heterogeneity, an important issue remains: What factors are relevant for the
      stability of surface color perception? Using stimuli with two fields of
      illumination, we explore this issue in three experiments. In Experiment 1, we
      manipulated the number of luminances, the number of reflectances, and the number
      of surfaces and their spatial relationships; in Experiment 2, we manipulated the
      luminance range; finally, in Experiment 3 we varied the number of surfaces
      crossed by the illumination edge. We found that there are two relevant factors in
      optimizing lightness constancy: (1) the lowest luminance in shadow and (2) the co
      presence of patches of equal reflectance in both fields of illumination. The
      latter effect is larger if these patches strongly belong to each other. We
      interpret these findings within the albedo hypothesis.

PMID- 16617835
TI  - Motion onset captures attention: a rejoinder to Franconeri and Simons (2005).
AB  - Recently, we have provided evidence that the onset of motion captures attention
      (Abrams & Christ, 2003, 2005a, 2005b). In the present article, we clarify the
      motion onset hypothesis, we discuss recent data (Franconeri & Simons, 2005) that,
      at least on the surface, seem to challenge the hypothesis, and we present results
      from a new experiment (Christ & Abrams, 2005). Finally, we conclude that,
      although motion onset does indeed appear to capture attention, motion in the
      absence of a motion onset might also attract attention under certain
      circumstances.

PMID- 16617836
TI  - Contribution of thermal cues to material discrimination and localization.
AB  - The objective of these two experiments was to determine the role of thermal cues
      in material discrimination and localization, using materials that spanned a range
      of thermal properties. In the first experiment, the subjects were required to
      select the cooler of two materials presented to the index fingers. In the second,
      the finger that was in contact with a material that was different from that
      presented to the other two fingers on the same hand had to be identified. The
      results indicated that the subjects were able to discriminate between materials,
      using thermal cues, when the differences in their thermal properties were large.
      The changes in skin temperature when the fingers were touching the materials
      were, however, smaller than those predicted by the theoretical model. The ability
      to localize the thermal changes when three fingers on the same hand were
      stimulated was poor and depended on both the thermal properties of the target and
      the distractor materials.

PMID- 16617837
TI  - The control of saccade trajectories: direction of curvature depends on prior
      knowledge of target location and saccade latency.
AB  - Recent reports have shown that saccades can deviate either toward or away from
      distractors. However, the specific conditions responsible for the change in
      initial saccade direction are not known. One possibility, examined here, is that
      the direction of curvature (toward or away from distractors) reflects preparatory
      tuning of the oculomotor system when the location of the target and distractor
      are known in advance. This was investigated by examining saccade trajectories
      under predictable and unpredictable target conditions. In Experiment 1, the
      targets and the distractors appeared unpredictably, whereas in Experiment 2 an
      arrow cue presented at fixation indicated the location of the forthcoming target
      prior to stimulus onset. Saccades were made to targets on the horizontal,
      vertical, and principal oblique axis, and distractors appeared simultaneously at
      an adjacent location (a separation of +/- 45 degrees of visual angle). On
      average, saccade trajectories curved toward distractors when target locations
      were unpredictable and curved away from distractors when target locations were
      known in advance. There was no overall difference in mean saccade latencies
      between the two experiments. The magnitude of the distractor modulation of
      saccade trajectory (either toward or away from) was comparable across the
      different saccade directions (horizontal, vertical, and oblique). These results
      are interpreted in terms of the time course of competitive interactions operating
      in the neural structures involved in the suppression of distractors and the
      selection of a saccade target. A relatively slow mechanism that inhibits
      movements to distractors produces curvature away from the distractor. This
      mechanism has more time to operate when target location is predictable,
      increasing the likelihood that the saccade trajectory will deviate away from the
      distractor.

PMID- 16617838
TI  - Strength of British English accents in altered listening conditions.
AB  - This work is concerned with the processing or representational level at which
      accent forms learned early in life can change and with whether alteration to a
      speaker's auditory environment can elicit an original accent. In Experiment 1,
      recordings were made of an equal number of (1) speakers living in the home
      counties (HC) of Britain (around the London conurbation) who claimed to have
      retained the accent of the region that they originally had come from, (2)
      speakers who stated that they had lost their regional accent and acquired an HC
      accent, and (3) native HC speakers. They read two texts in a normal listening
      environment. Listeners rated the similarity in accent between each of these texts
      and all the other texts. The results showed that in the normal listening
      conditions, the speakers who had lost their accent were rated as being more
      similar to HC English speakers than to those speakers from the same region who
      had retained their accent. In Experiment 2, recordings of the same speakers under
      frequency-shifted and delayed auditory feedback, as well as the normal listening
      conditions used earlier, were rated in order to see whether the manipulations of
      listening environment would elicit the speaker's original accent. Listeners rated
      similarity of accent in a sample of speech recorded under normal listening
      against a sample read by another speaker in one of the altered listening
      conditions. When listening condition was altered, the speakers who had lost their
      original accent were rated as more similar to those who had retained their
      accent. It is concluded that accent differences can be elicited by altering
      listening environment because the speech systems of speakers who have lost their
      accent are more vulnerable than those of speakers who have not changed their
      original accent.

PMID- 16617839
TI  - Infants' perception of depth from cast shadows.
AB  - Five- and 7-month-old infants viewed displays in which cast shadows provided
      information that two objects were at different distances. The 7-month-olds
      reached preferentially for the apparently nearer object under monocular-viewing
      conditions but exhibited no reaching preference under binocular-viewing
      conditions. These results indicate that 7-month-old infants perceive depth on the
      basis of cast shadows. The 5-month-olds did not reach preferentially for the
      apparently nearer object and, therefore, exhibited no evidence of sensitivity to
      cast shadows as depth information. In a second experiment, 5-month-olds reached
      preferentially for the nearer of two objects that were similar to those used in
      the first experiment but were positioned at different distances from the infant.
      This result indicated that 5-month-olds have the motor skills and motivation
      necessary to exhibit a reaching preference under the conditions of this study.
      The results are consistent with the hypothesis that depth perception based on
      cast shadows first appears between 5 and 7 months of age.

PMID- 16617840
TI  - [An address to young researchers].

PMID- 16617841
TI  - [Long-term experience with testing family and sexual contacts of HBsAg positive
      persons].
AB  - The study objectives were to identify HBsAg positive persons and to offer free
      vaccination against the infection to their family and sexual contacts found
      negative in screening for viral hepatitis B (VHB) postinfection markers. MATERIAL
      AND METHODS: Any person testing HBsAg positive in the Plzen region was registered
      in cooperation with laboratories. The collected data included reason for testing,
      clinical diagnosis and ethnicity. Contacts were screened for postinfection
      markers and vaccinated. RESULTS: Between 1997 and 2004, 939 HBsAg positive
      persons were registered by laboratories in the Plzen region. Their mean age was
      42.2 (0-90) years. As many as 63.4 % of the infected persons appeared to be
      "healthy" carriers. Nevertheless, a significant upward trend in HBsAg positivity
      was recorded among immigrants (mainly those from Vietnam). Altogether 18.2 % of
      829 family and sexual contacts tested positive for VHB postinfection markers
      (HBsAg, anti-HBc). The highest percentages of infected contacts were detected
      among siblings and parents of HBsAg positive persons (36.5 % and 27.3 %,
      respectively). Free vaccination has been requested by 82.2 % of susceptible
      contacts. CONCLUSION: Systematic vaccination of family and sexual contacts of
      HBsAg positive persons can contribute to more rapid VHB elimination in the Czech
      Republic. Currently, special attention in detecting infected persons is to be
      paid to immigrants from Asia.

PMID- 16617842
TI  - [West Nile virus fever].
AB  - West Nile virus (WNV) is a member of the Flaviviridae family, genus Flavivirus.
      Its reservoir hosts are wild birds. Infection is transmitted to humans by
      infected mosquitoes of the genus Culex. In most cases, it is either asymptomatic
      or manifests itself as mild fever. Typically, WNV illnesshas a sudden onset with
      fever above 39 degrees C and accompanying symptoms such as chills, headache,
      arthralgia, myalgia, back ache, cough and sore throat. Gastrointestinal symptoms
      are frequently reported. Generalized lymphadenopathy and conjunctivitis may
      develop. In some patients the infection can progress to meningoencephalitis.
      Diagnosis is currently based on detection of IgM antibodies in blood and
      cerebrospinal fluid or direct detection of WNV RNA.

PMID- 16617843
TI  - [Outbreak of Marburg hemorrhagic fever in Angola].
AB  - Marburg hemorrhagic fever is a rare acute viral fever illness with a serious
      clinical course often leading to a fatal outcome. The lethality rate ranges
      between 25 and 80 %. Both the virus reservoir and mode of transmission to humans
      are unknown. Close contact with body fluids of infected persons is prerequisite
      for secondary human to human transmission. Seriousness of the infection is
      underlined by the unavailability of specific treatment and vaccination. The
      outbreak in Angola in 2004-2005 accounted for the highest prevalence of the
      disease recorded to date. As many as 374 cases were reported by August 23, 2005,
      329 of these were fatal; the lethality rate was 88%. In comparison with the
      previous outbreaks, the afflicted area is unusually vast, includes populated
      zones, and intensive secondary transmission is observed.

PMID- 16617844
TI  - [Epidemiological characteristics of diabetes mellitus in Slovakia, 1992-2002].
AB  - Diabetes mellitus (DM) is one of the most important public health concerns and
      its consequences represent a considerable social and health burden. The study
      analyses the occurrence of DM in Slovakia in 1992-2002. MATERIAL AND METHODS: Age
      standardised incidence and prevalence rates of DM were calculated from the data
      published by the Institute of Health Information and Statistics for 1992, 1997
      and 2002. Disease length and the incidence of selected complications in 1997 and
      2002 were also analysed. RESULTS: In 1992-2002, DM prevalence in Slovakia
      increased from 4261.3 to 5065.8 cases per 100,000 population and appeared to be
      positively associated with age, while the DM incidence rates rose from 329.6 to
      423.7 cases per 100,000 population. In most patients, DM length was 5 years or
      less, showing an upward trend over the studied period. From 1997 to 2002, the
      rates of selected diabetic complications slightly increased (from 18.7 % to 20.3
      % for peripheral neuropathy, from 16.8 % to 18.0 % for retinopathy, from 7.1 % to
      8.0 % for nephropathy and from 1.2 % to 1.3 % for amputations). DISCUSSION AND
      CONCLUSIONS: Comparing with the world data, Slovakia ranks among the countries
      with relatively high prevalence of DM, mainly due to the rising incidence. These
      results are consistent with the global upward trend in DM. However, taking into
      account underreporting, the actual DM prevalence in Slovakia could be
      considerably higher. Besides primary prevention, risk reduction measures should
      be focused particularly on early diagnosis and better implementation of secondary
      prevention.

PMID- 16617845
TI  - [Medium with amikacin for laboratory diagnosis of beta-haemolytic streptococci].
AB  - Beta-haemolytic streptococci are implicated in the etiology of secondary wound
      infection, ulcerations and decubitus ulcers. Laboratory diagnosis of these
      causative agents is complicated by the fact that other less fastidious bacteria
      (Staphylococcus aureus, pseudomonads and enterobacteria) may also be involved in
      the infection. On blood agar, these bacteria overgrow colonies of beta-haemolytic
      streptococci. Detectability of beta-haemolytic streptococci on blood agar and
      selective blood agar added with, amikacin (36 microg/ml) was compared. A total of
      836 specimens from 782 patients were examined. Eighty-six isolates of beta
      haemolytic streptococci were detected. Coinfection with other bacterial species,
      most frequently identified as Staphylococcus aureus and Pseudomonas aeruginosa,
      was observed in 73 specimens. Forty-six isolates of beta-hemolytic streptococci
      involved in coinfection were detected on both blood agar and blood agar with
      amikacin. Twenty-seven additional isolates were only recovered on blood agar with
      amikacin. Without the use of selective medium, 37 % of isolates of beta
      haemolytic streptococci from skin lesion specimens would escape detection.

PMID- 16617846
TI  - The role of selenium in cancer and viral infection prevention.
AB  - The role of selenium, the essential trace mineral in human health and disease, is
      currently a subject of intense interest. The recent 30 years have been an
      exciting time in selenium research. Selenium has important health effects related
      to the immune response and cancer prevention, which are possibly not exclusively
      linked to their enzymatic functions. Selenium appears to be a key nutrient in
      counteracting the development of virulence and inhibiting HIV progression to
      AIDS. An elevated selenium intake may be associated with reduced cancer risk.
      Large clinical trials are now conducted both in Europe and the USA to confirm or
      reject this hypothesis. In the context of health effects, low or diminishing
      selenium status in some parts of the world, notably in some European countries,
      is giving cause for concern.

PMID- 16617847
TI  - Mortality from malignant neoplasms among workers of an asbestos processing plant
      in Poland: results of prolonged observation.
AB  - OBJECTIVES: The study on mortality from cancer among workers of an asbestos plant
      manufacturing asbestos yarn, cloth, cords, packings, stuffing, brake linings and
      asbestos-rubber sheets was launched in the 1980s. The present paper discusses the
      results of further tracing of asbestos workers of the same plant. MATERIALS AND
      METHODS: The study cohort covered 4497 workers employed at the asbestos plant in
      1945-1980. The follow-up of the cohort continued until 31 December 1999. Deaths
      by causes were analyzed using standardized mortality ratio (SMR) calculated by
      the person-years method. The mortality pattern of the general population of
      Poland was used as reference. RESULTS: The availability of the cohort was 93.1%
      (2805 men and 1382 women were traced). Mortality from malignant neoplasms in
      total (281 deaths among men, SMR = 118, 95%CI: 105-133 and 135 deaths among
      women, SMR = 159, 95%CI: 133-188) as well as that from lung cancer (102 deaths
      among men, SMR = 126, 95%CI: 103-153 and 18 deaths among women, SMR = 259, 95%CI:
      153-409) were significantly higher than in the general population. Unlike earlier
      stages of analysis, the present study revealed an increased risk of pleural
      mesothelioma (2 deaths among men, SMR = 510, 95%CI: 62-1842 and 3 deaths among
      women, SMR = 2033, 95%CI: 419-5941). Mortality analysis among workers with
      asbestosis and in those without diagnosed asbestosis, did not reveal direct
      association between the risk of asbestos-induced lung cancer and previously
      diagnosed asbestosis. CONCLUSIONS: The prolonged cohort tracing showed an
      increased risk of asbestos-related cancers. It concerned mainly workers hired by
      the plant between 1945-1955, when the working condition were most strenuous.

PMID- 16617848
TI  - Assessment of blood serum immunoglobulin and C-reactive protein concentrations in
      workers of x-ray diagnostics units.
AB  - OBJECTIVES: Workers of x-ray departments are occupationally exposed to long-term
      low levels of ionizing radiation. The aim of the study was to investigate the
      influence of occupational exposure of low-level x-ray radiation on immunoglobulin
      and C-reactive protein (CRP) concentrations in radiology workers. MATERIALS AND
      METHODS: In the study group of 41 x-ray department workers and the control group
      composed of 32 persons, immunoglobulins (IgM, IgG, IgA) and CRP concentrations
      were analyzed. The study group was subdivided by gender and smoking habit.
      RESULTS: A significant decrease in IgG level was found in the workers and the
      female subgroup. The same observation was made when smokers and nonsmokers of
      both groups were compared. Smoking workers showed lower concentrations of IgA
      than non-smokers. The remaining results of immunoglobulin and CRP concentrations
      did not show significant differences. CONCLUSIONS: Occupational exposure to low
      levels of ionizing radiation is associated with suppressive influence on the
      immunoglobulin production, especially IgG. In addition, smoking decreases the
      production of IgA in radiology workers.

PMID- 16617849
TI  - Identification of health hazards to rural population living near pesticide dump
      sites in Poland.
AB  - OBJECTIVES: The aim of the present project was to assess population exposure to
      pesticides in the vicinity of pesticide dump sites and make a preliminary
      evaluation of the potential health hazards to humans. MATERIALS AND METHODS: Of
      the 286 pesticide dump sites registered in Poland, 40 were selected as the
      largest source of ecological hazard. The application of the Hazard Ranking System
      made it possible to identify 17 priority dump sites where pesticide wastes are
      deposited. For population exposure assessment, two dump sites located close to
      the residence area and drinking water intakes were selected as potentially most
      hazardous to health. They have a piezometric system installation that enables
      ground water sampling for analysis. RESULTS: In water samples collected from the
      water-bearing layer in areas adjacent to pesticide dump site, 31 different
      pesticides in total have been detected (15 organochlorine pesticides, 10
      organophosphorous pesticides and 6 phenoxyacids), 12 of which - dichlorvos,
      mevinphos, endosulfan, dieldrin, heptachlor epoxide, p,p'-DDT, p,p'-DDD, p,p'
      DDE, methoxychlor, 2,4-D, MCPA, MCPP--had concentration levels higher than the
      detection limit. The estimated size of the potentially exposed population
      approximates 900 inhabitants; 33% of this population are children (aged 0-14
      years) and women at reproductive age (aged 15-45 years). Both these target
      populations are considered particularly susceptible to the adverse health effects
      of pesticides. Assessment of population exposure to pesticides (p,p'-DDT - 0.15
      microg/l; p,p'-DDD - 0.13 microg/1; MCPP - 12.3 microg/l; MCPA - 0.64 microg/l;
      methoxychlor - 0.31 microg/l; 2,4'-D - 5.4 microg/l) with concentration levels
      higher than the drinking water standard (0.1 microg/1) was based on pesticide
      daily intake in drinking water. CONCLUSIONS: The results indicated a low cancer
      risk (R = 10(-8)) for people drinking water contaminated with p,p'-DDT and p,p'
      DDD as well as low non-cancer risk related to MCPA, MCPP and methoxychlor
      exposure. At one of the dump sites examined, the level of population exposure to
      2,4'-D implies possible hematopoietic, nephrotoxic and hepatotoxic effects as
      well as reproductive disorders.

PMID- 16617850
TI  - Occupational voice disorders: an analysis of diagnoses made and certificates
      issued in 1999-2004.
AB  - OBJECTIVES: It has been decided to identify the most frequent diseases of the
      larynx in people occupationally exposed to a considerable voice load and to
      assess the feasibility of using videostroboscopy to diagnose voice disorders and
      their organic effects in order to improve the reliability of certification of
      occupational vocal organ diseases as well as to evaluate the functioning of new
      regulations on diagnosing and certifying occupational vocal organ diseases and to
      assay the conformity of clinical diagnoses made at voivodeship (provincial)
      centers (level I) with those made at scientific research institutes (level II).
      MATERIALS AND METHODS: The study involved an analysis of 1261 cases (1042 women
      and 219 men) with the vocal organ disorders referred to the ENT Unit, Nofer
      Institute of Occupational Medicine, Lodz, by voivodeship centers during 1999-2004
      for consultation or under the appeal procedure (if applicants were denied the
      right to be included in the category of patients with occupational disease of the
      vocal organ). The majority of the patients (65.7%) were primary school teachers,
      and those aged 51-60 years made 54.8%. Laryngological, phoniatric and
      videostroboscopic examinations, when necessary, supplemented with other testing
      procedures (paranasal sinus imaging, allergenic tests) were taken to assess the
      clinical state of the patients. RESULTS: As a result of these comprehensive
      examinations, organic changes in the larynx were detected in 161 (12.7%) cases,
      including 139 (11.0%) women and 22 (1.7%) men. According to current
      diagnostic/certifying criteria those pathologies could be classified into the
      category of occupational disease of the vocal organ. Paresis of vocal folds due
      to the insufficiency of vocal fold adductor and tensor muscles with permanent
      dysphonia was found in 97 (7.6%) patients, vocal nodules in 53 (4.2%) and
      secondary hypertrophy changes in vocal folds in 11 (0.87%) patients. The most
      frequent reasons for excluding the occupational etiology of the disease were
      functional disorders of the voice observed in 82.3% of patients in the form of
      hyperfunctional dysphonia (64.3%), hypofunctional dysphonia (17.0%) and
      dysfunctional dysphonia (about 1.0%). In 9.0% of patients, the functional
      disorders of the voice were accompanied by organic changes in the larynx caused
      by non-occupational factors. CONCLUSIONS: The analysis showed that due to new
      Polish regulations, the number of certified occupational disease of the vocal
      organ was reduced; videostroboscopic tests proved to be a very helpful tool for
      discriminating between the functional and organic disorders of the vocal organ;
      and good agreement between clinical diagnoses issued at both levels (I and II)
      was also revealed.

PMID- 16617851
TI  - Occupational energy expenditure and leisure-time physical activity.
AB  - OBJECTIVES: In the majority of countries around the world, a decrease in the
      leisure-time physical activity is observed. The aim of the study was to evaluate
      the correlation between occupational energy expenditure and leisure-time physical
      activity. Moreover, the correlation between other factors and leisure-time
      physical activity was assessed. MATERIALS AND METHODS: The study was performed in
      a randomly selected group of full-time employees (272 men and 236 women) living
      in the city of Lodz. Logistic regression was used to estimate odds ratios and 95%
      confidence intervals as well as to control the effects of occupational workload
      and leisure-time physical activity limitations. Physical activity was determined
      by the Seven Day Physical Activity Recall (SDPAR). RESULTS: Leisure-time physical
      activity was strongly associated with energy expenditure on occupational physical
      activity in men and women. Among men who expended 4000 kcal/week or more on
      occupational physical activity, the risk of inactivity at leisure was 1.5 times
      higher than in men whose weekly energy expenditure on occupational activity did
      not exceed 4000 kcal (adjusted OR = 1.33, 95% CI: 1.06-2.34). Among women who
      expended 3500 kcal/week or more on occupational physical activity, the risk of
      not taking up leisure-time physical activity was also higher as compared to those
      whose weekly energy expenditure on occupational activity was lower than 3500 kcal
      (adjusted OR = 1.41, 95% CI: 1.09-3.40). CONCLUSIONS: Prophylactic schedules
      associated with the improvement of leisure-time physical activity should be
      addressed to all adults, particularly to blue-collar workers. Future programs
      aimed at increasing physical activity in adults should consider work-related
      factors.

PMID- 16617852
TI  - Cardiovascular, hormone, and lipid responses to stress induced by virtual crane
      handling.
AB  - OBJECTIVES: The aim of the study was to test whether a mixed-mock-up-simulator
      (MMU-simulator) is suitable for on-the-job training by measuring stress reactions
      induced by handling a crane in a virtual environment in subjects not experienced
      in crane operation. MATERIALS AND METHODS: A MMU-simulator in a virtual
      environment was developed. Twenty three individuals were randomly divided into
      Group 1 (n = 13) and Group 2 (n = 10). They had the task of transporting a weight
      over barriers with a virtual crane twice in two 15-min intervals with a 15-min
      break in between. Acoustical and optical disturbances were generated as an
      additional strain for Group 1 in the second interval and for Group 2 in the first
      interval. Heart rate (HR) and blood pressure (BP) were measured consecutively in
      both groups, blood sampling was performed in Group 1. Plasma concentrations of
      stress hormones and lipids were analyzed. Data were calculated as the percentage
      of baseline values. RESULTS: Compared to rest courses, strain led to a
      significant increase in HR and BP except diastolic BP in Group 2. Apart from an
      increased systolic BP under additional stress in Group 2, no significant
      differences were found between the two strain courses. Concentrations of
      epinephrine showed the highest increase under strain with a mean of 67%. The mean
      increase in norepinephrine and cortisol was 23% and 7%, respectively, whereas a
      4% increase was observed for total cholesterol and high density lipoprotein
      cholesterol. These differences between "Rest" and "Strain" were significant.
      After adjusting for total plasma protein concentration, stress hormones, but not
      lipids, were still significantly higher during strain. CONCLUSIONS: The elevation
      in lipids during acute stress could be interpreted as an effect of
      hemoconcentration due to vasoconstriction by catecholamines. The significant
      increase in cardiovascular parameters and stress hormones during the tasks
      demonstrate that working in a virtual environment generates mental strain and
      that the developed MMU-simulator appears to be a promising device for on-the-job
      training. However, further research is necessary to validate the usefulness of
      virtual training by means of a comparative study of virtual and real-world
      training.

PMID- 16617853
TI  - Anxiety about professional future among young doctors.
AB  - OBJECTIVES: The interest is focused on today's interns who will soon become an
      essential part of the health care system. Obstacles they perceive at the
      beginning of the career may encourage them or, inversely, impede their
      professional development, enhance professional burnout or even lead to change of
      the profession. International literature, comprising publications on the
      situation in ten European countries, Canada and the USA, is reviewed. Numerous
      considerations have encouraged some attempts to measure "anxiety about
      professional future" (AAF). MATERIALS AND METHODS: Seven factors that induce
      anxiety about professional future among students and young doctors are listed and
      briefly discussed: 1) Difficulties in getting a job and growing anxiety for
      maintaining the job; 2) Low wages; 3) Negative impact of work on private and
      family life, in particular, a conflict between the professional role and mother's
      role; 4) Excessive level of organizational stress; 5) Lack of (individual)
      resources to cope with stress; 6) Institutional and financial limitations for
      professional development; and 7) Worldwide evolution of the professional role and
      the status of doctor. A questionnaire was developed by the author and answers
      were collected from a representative sample of Polish interns (about 1000) and a
      small sample of French interns. A scale for measuring the anxiety was built with
      use of factor analysis. RESULTS: The resulting scale called AAF has proved to
      have good statistical properties. The mean value of the anxiety indicator proved
      to be high in Poland. Interns who are familiar with the doctor's daily duties,
      who feel economically independent and who have good self-valuation of the
      practical skills are characterized by a lower level of anxiety. AAF values in a
      sample of French interns was dramatically lower than those characteristic of
      Polish interns. CONCLUSIONS: The values of AAF for the interns can be related to
      the intensity of stress-inducing factors in the professional environment. Very
      high AAF values can stem from an excessive professional stress that may have a
      negative impact on individual careers and the whole health care system in Poland.
      Appropriate changes in the curriculum of medical studies (accompanied by legal
      regulations) might reduce excessive anxiety about future in graduating doctors in
      Poland. Such changes could include: (a) a greater involvement of students in the
      examination and treatment of patients and in "daily life" in health care
      institutions; (b) making more practice (or performing medical procedures)
      obligatory; (c) creating better opportunities to earn living in the medical
      professions (by performing procedures or by assisting professionals); and (d)
      making efforts in the field of practical education more rewarding (e.g.,
      introducing rating for practice and incorporating it into fellowship schemes).

PMID- 16617854
TI  - Temporary hearing threshold shift measured by otoacoustic emissions in subjects
      exposed to short-term impulse noise.
AB  - OBJECTIVES: The aim of the study was to assess the influence of short-term
      impulse noise on the size and dynamics of temporary threshold shift, which
      precedes permanent threshold shift, i.e. noise-induced hearing loss. It was hoped
      to use the findings for preventive activities. MATERIALS AND METHODS: The study
      included 80 healthy subjects (160 ears), aged 19-23 years, divided into two
      groups: group I comprised 40 recruit soldiers put to the shooting training, and
      group II consisted of 40 young male controls. All subjects had to show normal
      hearing with pure tone audiometric thresholds between 10-15 dB. Transient evoked
      otoacoustic emission (TOAE) measurements were performed by ILO 292 Echoport
      Otodynamics device 3-5 min before shooting and then 2 min, 1, 2 and 3 h,
      respectively after shooting. In group II the time intervals were similar.
      RESULTS: It was found that the gunshot impulse noise from the kbk AKMS rifle
      caused temporary hearing threshold shift (TTS) at 1, 2, 3, 4 and 5 kHz
      frequencies of 1.07, 0.96, 1.41, 0.88 and 1.25 dB SPL, respectively. TIS turned
      out to be maximum at 4 and 5 kHz and minimum at 1 and 2 kHz. CONCLUSIONS: Short
      term impulse noise generated by the rifle gunshots induces rather small temporary
      threshold shift of hearing. Anyhow, considering possibilities of different weapon
      noises in the military environment as well as various sources of industrial
      impulse noise, the usage of hearing protectors should be highly recommended.

PMID- 16617855
TI  - Polish bibliography of occupational medicine, 2004.

PMID- 16617856
TI  - [Adrenal effect of inhaled corticosteroids in adult asthmatic patients].
AB  - Inhaled corticosteroids (ICS) are usually well tolerated with smaller systemic
      effects than intravenous steroids, however, when the dose is high the likelihood
      of steroid-related systemic side effects like hypothalamic pituitary adrenal
      (HPA) axis suppression and osteoporosis are reported. We reviewed HPA axis
      suppression related to different ICS characteristics by affinity to steroid
      receptor and their pharmacokinetics, and also reviewed by randomized, controlled
      clinical trials. Within the approved dosages for each ICS in Japan, HPA axis
      suppression is basically minimal and clinically negligible.

PMID- 16617857
TI  - [Noninvasive positive pressure ventilation in patients with acute exacerbations
      of pulmonary tuberculosis sequelae].
AB  - To clarify whether noninvasive positive pressure ventilation (NPPV) is effective
      in patients with acute exacerbations of pulmonary tuberculosis sequelae (PTS), 50
      PTS patients (66 episodes) without long-term domiciliary noninvasive ventilation
      were studied, retrospectively. The average values (SD) of their pulmonary
      function tests and arterial blood gases were as follows; %predicted VC = 31.4
      (8.4)%, pH = 7.29 (0.06), PaCO2 = 91.8 (19.7) mmHg, and PaO2 = 64.2 (20.3) mmHg.
      The probability of avoiding endotracheal intubation and recovering from an acute
      exacerbation with NPPV (NPPV success rate) was 92% as a whole. NPPV success rates
      according to the causes of deterioration were as follows; 96% in 26 episodes with
      only a simple right heart failure, 93% in 29 episodes with airway infectious
      diseases, 75% in eight episodes with pneumonia and/or acute respiratory distress
      syndrome. Moreover, the NPPV success rate of eight episodes in coma or semicoma
      was 88%. Most patients were treated in respiratory wards rather than intensive
      care units. Out of 46 patients who recovered from an acute exacerbation, 41
      finally received domiciliary NPPV. In facilities where staff are well-trained for
      an acute NPPV, patients with exacerbations of PTS can be treated as successfully
      with NPPV as patients with COPD.

PMID- 16617858
TI  - [Fungal culture from pharyngeal swab and seasonal influence in patients with
      chronic non-productive cough].
AB  - It has been suggested that Basidiomycetes is an important fungal aeroallergen. We
      have reported that Basidiomycetes may be important for allergic airway disorders
      such as atopic cough, cough variant asthma and bronchial asthma. In this study,
      141 patients with chronic nonproductive cough underwent pharyngeal swab culture
      for fungi, and 18.4% of all patients were positive for Candida (10.6%) and
      Basidiomycetes (6.4%). Positive results for Basidiomycetes culture were
      relatively frequent in August and September. It is suggested that Basidiomycetes
      is important as a fungus colonizing in the pharynx, and that of causative and/or
      exacerbating for allergic airway disorders presenting with chronic non-productive
      cough.

PMID- 16617859
TI  - [A case of primary pulmonary MALT lymphoma with diffuse micronodules and anemia].
AB  - A 52-year-old woman presented with low grade fever and fatigue. She had diffuse
      micronodules in both lung fields on chest X-ray. Chest CT showed diffuse multiple
      small nodules. Laboratory examination revealed high values for C-reactive
      protein, together with anemia and polyclonal hyper-immunoglobulinemia and an
      elevated interleukin-6 level. Although we suspected multicentric Castleman's
      disease, thoracoscopic lung biopsy revealed primary pulmonary MALT lymphoma by
      immunohistochemical analysis of tissue specimens. After COP and rituximab
      therapy, partial remission was obtained.

PMID- 16617860
TI  - [A case of interstitial pneumonia accompanying SIADH].
AB  - A 75-year-old man was transferred to our hospital on November 28, 2003 because of
      acute aggravation while being treated for interstitial pneumonia superimposed on
      pneumoconiosis at a local hospital. Upon admission, oxygen inhalation therapy and
      antimicrobial chemotherapy were started for the interstitial pneumonia. In
      addition, since he showed hyponatremia from admission, a saline load was
      administered and the clinical course was observed. However, disturbance of
      consciousness developed on January 5, 2004. At that time, the serum sodium was
      115mEq/l. Since secretion of antidiuretic hormone (SIADH) had continued despite a
      low plasma osmolarity, we diagnosed syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH). We initiated treatment with water restriction and
      saline load, but no remarkable improvement was observed. From February 7, 40mg
      /day prednisolone was started because of aggravation of interstitial pneumonia.
      As a result, the respiratory status and image findings improved, and serum sodium
      level was normalized. This case was considered to be SIADH secondary to
      interstitial pneumonia. Among respiratory tract diseases, SIADH is often caused
      by small cell lung carcinoma, although it may also occur concurrently with other
      respiratory tract diseases. Since hyponatremia may manifest grave disturbance of
      consciousness, investigation of the cause is important.

PMID- 16617861
TI  - [An autopsy case of myelodysplastic syndrome complicated by recurrent organizing
      pneumonia].
AB  - We reported an autopsy case of a 58-year-old-man, who developed intractable
      organizing pneumonia accompanying myelodysplastic syndrome with neutrophil
      hypofunction. Slight clinical improvement was obtained by steroid pulse therapy,
      but re-exacerbation occurred during steroid tapering. Infection was suspected,
      and we administered antibiotics and antifungal agents, while holding steroid
      administration. However, both the clinical findings and images deteriorated. By
      both steroid and cyclosporine treatment, a slight improvement was temporarily
      obtained, but he died. The findings of lung tissue on autopsy showed extensive
      old and new organized pneumonia, and, as for the etiology of the intractable
      pneumonia, the likelihood of the lung infectious disease was considered most
      likely. In addition, invasive pulmonary aspergillosis led directly to death.

PMID- 16617862
TI  - [A case of volcanic ash lung: report of a case].
AB  - A 57-year-old woman inhaled much volcanic ash without using a mask every day
      during the eruption of the Miyake Volcano in August 2000. An abnormal shadow was
      pointed out on her chest radiography by chance, after she sought refuge in
      Higashimurayama city in September. She had no respiratory symptoms and her chest
      radiography in an annual health check in July 2000 had showed no abnormality. She
      was admitted to our hospital and thoracoscopic lung biopsy was performed. We
      diagnosed it as lung inflammation caused by volcanic ash. The reasons for
      diagnosis were because the abnormal shadow appeared after the inhalation of
      volcanic ash, chest computed tomography showed diffuse irregular shadows with air
      bronchogram, thoracoscopic lung biopsy showed cellular-bronchiolitis around
      crystals, and the results of mineralogical analysis of the particles in alveolar
      macrophages detected in the biopsy specimen by scanning electron microscopy (SEM)
      were very similar to those of volcanic ash. The shadow on her chest radiography
      disappeared gradually without any treatment, but she avoided further exposure to
      volcanic ash. It is necessary to consider volcanic ash capable of causing lung
      inflammation.

PMID- 16617863
TI  - [Obstructive sleep apnea syndrome in a patient with superior vena cava syndrome
      caused by malignant lymphoma].
AB  - A 52-year-old man was given emergency admission because of progressive facial
      edema and dyspnea. Chest X-ray film on admission showed a large hemispherical
      mass in the right paratracheal region. Chest CT scan showed a large tumor in the
      mediastinum, narrowing of the trachea and superior vena cava. Severe snoring at
      night and excessive daytime sleepiness were noticed. Obstructive sleep apnea
      syndrome (OSAS) was diagnosed by polysomnogram (PSG). Although a histological
      diagnosis of the tumor was not established, chest irradiation was begun to reduce
      the size of tumor. After treatment, the mediastinal tumor almost completely
      disappeared, and the facial swelling and snoring were gradually relieved. PSG
      showed remarkable improvement of the apnea-hypopnea index (AHI). These findings
      suggested a significant correlation between SVCS and OSAS. After three months,
      right inguinal lymphadenectomy was done and it was diagnosed as malignant
      lymphoma (mantle cell lymphoma). OSAS may cause a deterioration of respiratory
      symptoms and the quality of life in a patient with SVCS. Therefore, in the case
      of SVCS, it is important to take account of the presence of OSAS and select an
      appropriate treatment.

PMID- 16617864
TI  - [A case of primary lung cancer complicated with hypothyroidism by diffuse thyroid
      metastasis].
AB  - A 56-year-old woman with hypothyroidism was admitted to our hospital because of
      an abnormal chest X-ray film. The chest CT showed a 3-cm spiculated tumor in the
      left lingual branch, and multiple nodular shadows with random distribution.
      Cervical CT showed diffuse enlargement of the thyroid gland with low density. The
      cytology of the tumor in the left lingular branch revealed adenocarcinoma, and
      ultrasound-guided fine needle aspiration cytology of the thyroid gland revealed
      adenocarcinoma, cytologically identical to the cells from bronchoscopic
      examination. Immunochemically, specimens obtained from both bronchoscopy and the
      thyroid gland were negative for thyroglobulin. Therefore, we diagnosed this case
      as primary lung cancer complicated with hypothyroidism by diffuse metastasis of
      the thyroid gland. Metastatic thyroid tumor is rarely diagnosed clinically.
      Furthermore, metastatic thyroid tumor complicated with thyroid dysfunction is
      extremely rare. We conclude that in patients with both diffuse thyroid swelling
      and thyroid dysfunction, the possibility of metastatic thyroid tumor should be
      considered.

PMID- 16617865
TI  - [Fatal invasive pulmonary aspergillosis triggered by influenza B virus infection
      in an individual with idiopathic pulmonary fibrosis].
AB  - A 56-year-old man with idiopathic pulmonary fibrosis developed acute symptoms,
      including fever and cough. Chest X-ray and CT scan films revealed consolidations
      and ground glass opacities in the bilateral lungs suggestive of massive pneumonia
      and acute respiratory distress syndrome (ARDS). Microscopic examination by a
      transbronchial lung biopsy from the right middle lobe demonstrated numerous
      hyphae of aspergillus. Despite treatment with anti-fungal agents, respiratory
      failure rapidly progressed, and the patient died on the 21st hospital day.
      Postmortem examination of the lung showed multiple abscesses with hyphae of
      aspergillus invading into small pulmonary artery and alveoli, which were the
      characteristic findings of invasive pulmonary aspergillosis (IPA). In addition,
      diffuse alveolar damage was also present, associated with the typical features of
      UIP such as honeycombing in the bilateral lungs. The serum anti-influenza B virus
      antibody was high at 512-fold. Therefore, it was speculated that influenza B
      virus infection triggered superimposed aspergillus infection leading to fatal IPA
      associated with ARDS.

PMID- 16617866
TI  - [A case of non-small cell lung cancer accompanied with hemorrhage after
      chemotherapy including gemcitabine].
AB  - A 51-year-old man underwent left upper lobectomy due to pulmonary adenocarcinoma
      (cT2N1M0, stage IIB) in August, 2003. Since he turned out pT2N3M0 stage IIIB, he
      received combination chemotherapy with carboplatin and gemcitabine. During a
      second course chemotherapy, he was admitted again because of dyspnea and the
      deterioration of diffuse interstitial shadows in both lungs. He was treated with
      various antibiotics and corticosteroids. Unfortunately, he could not recover. An
      autopsy was performed. Microscopic features of the lung revealed diffuse alveolar
      damage and pulmonary hemorrhage. In this case, pulmonary hemorrhage should be
      considered as a complication of gemcitabine-induced lung injury.

PMID- 16617867
TI  - [Clinical evaluation of urinary NMP22 (nuclear matrix protein 22) bladder chek in
      the detection of patients with bladder cancer].
AB  - The clinical usefulness of the nuclear matrix protein 22 (NMP22) Bladder Chek
      test as a novel urine marker in the detection of patients with bladder cancer was
      evaluated in comparison with the urinary NMP22 enzyme-linked immunosorbent assay
      (ELISA) and urinary cytology. A total of 40 patients with pathologically proven
      bladder cancer voided urine specimen before treatment. The urine samples were
      divided for NMP22 Bladder Chek test, NMP22 ELISA, and urinary cytology. In the 40
      patients with bladder cancer, the overall positive rate was 62.5% for the NMP22
      Bladder Chek test, 55% for the NMP22 ELISA test, and 27.5% for urine cytology.
      There was a significant difference between NMP22 Bladder Chek, NMP22 ELISA and
      cytology. The positive rate with the NMP22 Bladder Chek and NMP22 ELISA was
      higher in the patients with high grade and large-size (1 cm < or =) tumor. In 40
      patients presenting with microhematuria without urothelial cancer, the false
      positive rate 12.5, 10, and 0% for NMP22 Bladder Chek, NMP22 ELISA, and urinary
      cytology. No significant difference was found with the test. In conclusion, the
      urine NMP22 Bladder Chek test provided a higher positive rate than the NMP22
      ELISA test and urinary cytology. Therefore, the NMP22 Bladder Chek test may be
      clinically more useful as a tumor marker for the diagnosis of bladder cancer.

PMID- 16617868
TI  - [A large amount of distilled water ineffective for prevention of bladder cancer
      cell implantation at the time of transurethral resection].
AB  - A previous study indicated that distilled water could prevent bladder tumor cell
      implantation in an in vitro assay. We investigated whether a large amount of
      distilled water irrigation prevented recurrence of superficial bladder cancer in
      the clinical setting and then we estimated whether cancer cell implantation at
      the time of transurethral resection is a major mechanism of recurrence. Between
      May 2000 and January 2002, 22 patients with primary, superficial bladder
      carcinoma who underwent transurethral resection of bladder tumors (TURBT) were
      enrolled in this study. The patients underwent bladder washout with 1,000 ml
      distilled water immediately after TURBT, and then intravesical irrigation with
      3,000 ml water for three hours. Control patients were randomly chosen from those
      who previously underwent TURBT in our hospital and had similar prognostic
      factors. The 1- and 2-year recurrence-free rates in the patients undergoing
      distilled water irrigation were both 45% and those in the control patients were
      65% and 45%, respectively. There were no significant differences between the two
      groups. This result indicates that distilled water was ineffective in preventing
      recurrence of superficial bladder tumor.

PMID- 16617869
TI  - [Prognosis of prostate cancer with elevated prostatic acid phosphatase].
AB  - To evaluate the significance of prostatic acid phosphatase (PAP), we analyzed
      1,029 prostate cancer patients who were treated at the Niigata Cancer Center. We
      classified clinically localized prostate cancer with elevated PAP as stage DO.
      When stage DO was not taken into acount, the 5-year cause-specific survival rate
      for stage A, B, C and D was 94.7, 97.9, 87.7 and 42.4%, respectively. Taking
      stage DO into account, the cause-specific survival curve for stage DO patients
      was similar to those for stage B,C patients. The 5-year cause-specific survival
      rate for stage DO was 92.2% considering above 3 ng/ml as elevated PAP. A
      significant correlation was found between PAP and cause-specific survival for all
      cases but no correlation was found for non-metastatic disease patients. The
      significance of PAP in the staging of prostate cancer is limited.

PMID- 16617870
TI  - [Prostate cancer detection by prostate biopsy among Japanese with prostate
      specific antigen below 4.0 ng/ml].
AB  - The cases of prostate cancer diagnosed at our hospital after the introduction of
      transrectal ultrasound-guided prostate biopsy were analyzed to ascertain the
      cancer detection rate among individuals with a prostate-specific antigen (PSA)
      below 4.0 ng/ml and to assess the pathological characteristics of the
      prostatectomy specimens. During the period from January 1997 to December 2003,
      1,167 individuals received prostate biopsies at our hospital. Before March 2003,
      the PSA cut-off level for biopsy was set at 4.0 ng/ml, but a biopsy was sometimes
      performed if a rectal examination revealed abnormalities or the patient desired a
      biopsy with a PSA below 4.0 ng/ml. After April 2003, all individuals with a PSA
      over 3.1 ng/ml were biopsied. The results of the prostate biopsy and the
      pathology data on radical prostatectomy specimens were compared between
      individuals with a PSA below 4.0 ng/ml and those with a PSA of 4.1-10 ng/ml. The
      prostate cancer detection rate among individuals with a PSA between 3.1 and 4.0
      ng/ml was 19.4% (12/62) before March 2003 and 15.6% (7/45) after April 2003. The
      number of cancer-positive core was significantly lower among individuals with a
      PSA below 4.0 ng/ml. On prostatectomy specimens the percentage of surgical margin
      positive cases was significantly higher among individuals with a PSA below
      4.0ng/ml (17 cases) than those with a PSA of 4.1-10 ng/ml (67 cases), although
      there was no significant difference between these two groups in terms of the
      pathological stage and Gleason score. Our results indicate that the prostate
      cancer detection rate is also high among Japanese men with a PSA below 4.0 ng/ml.
      The biopsy results and pathological features for prostate cancer with a PSA below
      4.0 ng/ml did not differ markedly from prostate cancer with a PSA in the gray
      zone (4.1-10.0 ng/ml).

PMID- 16617871
TI  - [Clinical significance of cystoscopy in transrectal prostate biopsy].
AB  - The clinical significance of cystoscopy in patients with benign prostatic
      hyperplasia or prostate cancer remains open to discussion. We have always
      performed cystoscopy with prostate biopsy and have discovered bladder cancer in
      some patients. The present study investigated the clinical significance of
      performing cystoscopy with prostate biopsy. Subjects were 458 patients who
      underwent cystoscopy and ultrasound-guided transrectal prostate biopsy from
      January 1998 to December 2004. Mean age of subjects was 71.3 years (range, 52-93
      years). Prostate biopsy was performed modified Eskews systematic 5-region
      prostate biopsy (12 core). Some abnormalities were found in 43 of the 458
      patients (9.3%). Among these 43 patients, bladder cancer was found in 11 patients
      (2.4%), and transurethral resection bladder tumor (TUR-Bt) was performed on all
      11 patients. Pathological staging of bladder cancer was pT1 and G2 in all cases.
      Bladder stones were seen in 13 patients (2.8%), benign bladder tumor in 5
      patients (1.1%), urethral polyp in 7 patients (1.5%), urethral stenosis in 6
      patients (1.3%) and ureteral stones associated with ureterocele in 1 patient
      (0.2%). Appropriate examinations and treatments were performed for all cases.
      Cystoscopy may be needed at the time of prostate biopsy because: the above
      mentioned abnormalities were first discovered on cystoscopy; and the frequency of
      bladder cancer was 2.4% for the total patient population, and endoscopic surgery
      was performed.

PMID- 16617872
TI  - Lower urinary tract symptoms in 1,912 apparently healthy persons of both sexes.
AB  - We aimed to evaluate lower urinary tract symptoms (LUTS) in apparently healthy
      persons of both sexes using the International Prostate Symptom Score (IPSS) and
      quality of life index (IPSS-QI) as related to aging. A total of 1,912 apparently
      healthy participants (1,052 women and 860 men) were enrolled in this study. They
      were informed as to the nature of the study and asked to fill out the IPSS
      questionnaires. The mean age of women was 46.8 years (range 18.0 to 83.0) and
      that of men was 48.5 years (range 19.0 to 76.0). The storage and voiding symptom
      scores gradually increased in parallel with increasing age in both sexes. The
      proportion of participants with moderate to severe symptoms (IPSS 8 or greater)
      increased from 5.6% in women younger than 30 years to 8.9, 15.7, 20.8, 21.0% and
      28.6% for women 30 to 39, 40 to 49, 50 to 59, 60 to 69 and 70 years or older,
      respectively; the corresponding distribution for men was from 8.8 to 15.9, 18.7,
      38.1, 48.6 and 68.8%, respectively. In both sexes, the majority of persons showed
      1 or less nocturia. The distribution of IPSS-QI was very similar within each
      category of the IPSS severity in both sexes, showing that LUTS was equally
      bothersome to both sexes. These data should be taken into account to evaluate
      LUTS in both sexes.

PMID- 16617873
TI  - [The efficacy of Gosyajinkigan for pollakisuria].
AB  - We investigated the efficacy of Gosyajinkigan in 20 patients with prostatic
      disease, in whom pollakisuria was not improved by treatment with drugs for lower
      urinary tract symptoms. Four and 8 weeks after treatment, the urinary frequency
      was significantly improved during both daytime and night. The efficacy rates for
      diurnal frequency and nocturia were 45% and 65%, respectively. The International
      Prostate Symptom Score (IPSS) was decreased 4 weeks after treatment, and the
      parameters of uroflowmetry, the residual urine volume and quality of life score
      were improved 8 weeks after therapy. It was concluded that Goshajinkigan was
      effective for pollakisuria with prostatic disease, and the administration of the
      agent for 8 weeks or longer was needed to improve lower urinary tract symptoms.

PMID- 16617874
TI  - [Retroperitoneal liposarcoma: a case report].
AB  - We report a case of retroperitoneal liposarcoma. A 66-year-old male was referred
      to our hospital for a retroperitoneal tumor that was detected during gallbladder
      stone examination. Computed tomography (CT) and magnetic resonance imaging (MRI)
      revealed an extrarenal lipomatous tumor, 20 x 14 x 8 cm in size, in the right
      retroperitoneal space. He underwent surgical excision of the tumor with
      concomitant resection of the right kidney and adrenal gland. The resected tissue
      weighed 730 g. Histological examination revealed a well differentiated
      liposarcoma. He received no adjuvant therapy.

PMID- 16617875
TI  - [A case of retroperitoneal malignant peripheral nerve sheath tumor in a patient
      with neurofibromatosis].
AB  - We report a case of retroperitoneal malignant peripheral nerve sheath tumor
      (MPNST) in a patient with neurofibromatosis 1. A 42-year-old woman was admitted
      because of a palpable left abdominal mass. Her mother, son, and daughter had
      neurofibromatosis 1. Computed tomography and magnetic resonance imaging revealed
      a 73 x 76 mm retroperitoneal mass. We performed complete resection of the tumor,
      confirming the margin status by frozen section examination intraoperatively. The
      histopathological examination revealed MPNST. Although no further therapy was
      performed, she is alive with no evidence of disease 11 months after surgery.

PMID- 16617876
TI  - [A case of idiopathic retroperitoneal fibrosis accompanied by asynchronous
      bilateral urinoma].
AB  - The patient was a 68-year-old female with the complaint of left flank pain. On
      examination, hydronephrosis of the left kidney and the urinoma of left
      retroperitoneal space were disclosed by abdominal computed tomographic (CT) scan.
      The urinoma disappeared spontaneously, but 4 months later right hydronephrosis
      and the urinoma of ipsilateral retroperitoneum emerged. Enhanced CT scan revealed
      aneurysm of bilateral common iliac arteries and perianeurysmal fibrotic mass.
      After steroid therapy under the diagnosis of idiopathic retroperitoneal fibrosis
      (IRPF), the fibrotic mass reduced in size and the urinoma disappeared. We should
      be aware that urinomas, which are thought to be caused by sudden obstruction of
      the upper urinary tract, could be brought about by IRPF.

PMID- 16617877
TI  - [A case of renal capsular hemangiosarcoma].
AB  - We report herein a case of renal capsular hemangiosarcoma. A 68-year-old man was
      admitted to our hospital for treatment of a retroperitoneal tumor identified
      incidentally on abdominal computed tomography (CT) for follow-up of superficial
      bladder tumor. The tumor was about 7cm in diameter, positioned between the right
      kidney and the liver. Right nephrectomy was performed under a diagnosis of renal
      capsular tumor. Pathological diagnosis was hemangiosarcoma and positive surgical
      margins were suspected. Radiotherapy was performed postoperatively to a total
      dose of 50 Gy. Hemangiosarcoma frequently occurs in the skin, but is rare in the
      retroperitoneal cavity. Neither metastasis nor recurrence has been seen as of 19
      months postoperatively.

PMID- 16617878
TI  - [A seminal vesicle cyst treated by transurethral resection: a case report].
AB  - A 40-year-old man with dysuria was referred to our department on November, 18,
      2004. A transabdominal ultrasonography revealed a cystic mass arising from his
      bladder neck. Computed tomography and magnetic resonance imaging revealed the
      cyst to be homogeneous and ovally shaped with a clear margin. Bilateral
      vasography showed the compression of the left seminal vesicle by the cyst and
      there was communication between the cyst and the left seminal vesicle for
      diagnosis of the seminal vesicle cyst, percutaneous needle aspiration was
      performed. The aspirated fluid included microscopical spermatozoa and proved
      negative for cytology. Absolute ethanol was injected into the cyst and
      transurethral unroofing of the cyst was performed on January 14, 2005. The
      prostate was resected until we reached into the cyst.

PMID- 16617879
TI  - [The recurrence of urothelial carcinoma in situ at the fossa navicularis of the
      urethra and the glans penis arising eight years after transurethral resection of
      a bladder tumor to treat superficial bladder cancer].
AB  - A 63-year-old man underwent transurethral resection of a bladder tumor to treat
      superficial bladder cancer in 1995. Histological examination showed urothelial
      carcinoma, G2>G3 with carcinoma in situ (CIS) at the bladder neck. He underwent
      postoperative intravesical bacillus Calmette-Guerin (BCG) therapy. In June, 2003,
      he complained of rubor of his external urethral meatus and visited our clinic.
      Biopsies at the external urethral meatus and the fossa navicularis of the urethra
      showed CIS. Radiological examinations, cystourethroscopy and multiple biopsies
      from other sites of urothelium, including bladder and urethral mucosa, did not
      reveal any other malignancies. Thereafter, partial penectomy and bilateral
      inguinal lymphadenectomy were performed. Histological examinations showed CIS at
      the urethral mucosa of the fossa navicularis and the skin of the glans penis.
      Postoperative urine cytologies were negative.

PMID- 16617880
TI  - [A case of liposarcoma of spermatic cord].
AB  - An 84-year-old male was referred to our hospital with the chief complaint of a
      painless inguinal mass. An elastic hard mass was palpable in the right inguinal
      region next to the spermatic cord. Ultrasonography and computed tomography showed
      an inguinal homogeneous mass which was slightly enhanced. Since the operation
      appearance indicated the tumor was arising from the right spermatic cord, right
      radical orchiectomy was performed. Histopathological examination revealed a well
      differentiated liposarcoma of the right spermatic cord. This is the 70th case of
      liposarcoma of the spermatic cord reported in Japan.

PMID- 16617881
TI  - [Experience of laparoscopic nerve-sparing radical cystectomy and construction of
      ileal neobladder at Kansai Medical University].
AB  - Laparoscopic nerve-sparing radical cystectomy and construction of ileal
      neobladder was performed on a 76-year-old man with atrophic bladder after the
      intravesical instillation therapy for bladder cancer. Ileal neobladder was
      constructed by the combined extracorporeal technique through the camera port
      dilated to 45 mm. Operation time was 8 hours, with 3.5 hours for the nerve
      sparing cystoprostatectomy, 2.5 hours for the extracorporeal neo-bladder
      construction and 2 hours for the laparoscopic urethra neo-bladder anastomosis and
      wound closing. The post-operative course was uneventful with minimum use of
      analgesia. This operation was minimally invasive therapy and from the functional
      aspect the potency was preserved. Although this method was technically
      challenging, various advantages can be promising for the patients compared to the
      standard open technique. Indication of this operation should be carefully
      expanded. Various methods, such as the complete intracorporeal technique and
      minimally invasive laparoscopic neobladder (MILaN) technique, have been reported
      for urinary diversion. In this report, we compared our method with other
      techniques.

PMID- 16617882
TI  - The blinking blue schoolmarm. Eat your peas! Raise your kids right! Why is my TV
      trying to run my life?

PMID- 16617883
TI  - Tongue thrust and its influence in orthodontics.
AB  - The oral myofunctional disorder of tongue thrust has been described in various
      ways, such as 'deviate swallow' 'infantile swallow, and 'abnormal swallow' to
      name a few. The term 'tongue thrust' has been adopted, mainly because of its
      greater usage among authors, and since it gives a more accurate description of
      the lingual behavior about to be discussed. 'Tongue thrust' and 'tongue
      thrusting' are used in preference to 'tongue thrust swallow' or 'tongue thrust
      swallowing' because this behavior is generally thought to be less associated with
      the act of swallowing and more with the resting posture of the tongue. 'Thrust'
      is still an inappropriate word since the tongue is not really 'thrusting' during
      rest. However, it must be remembered that 'thrusting' in this instance is still a
      mild but continuous lingual pressure factor. The significance lies in whether or
      not this 'thrust, either during swallowing and other functional behaviors, or
      during rest, is responsible for, contributes to, or is a consequence of the
      development of a malocclusion.

PMID- 16617884
TI  - Cranial strains and malocclusion: IV. Torsion.
AB  - The cranial strain known as torsion does not fit within the Angle Classification.
      This strain is described and how to identify it. Torsion may occur as the only
      strain or is more commonly superimposed on another strain. Recognizing the
      presence of a torsion has a significant bearing on treatment sequencing. An
      approach to treatment is demonstrated.

PMID- 16617885
TI  - Multidimensional cases: thinking out of the box!

PMID- 16617886
TI  - Brainstorming.

PMID- 16617888
TI  - So...you've been asked to be a speaker?

PMID- 16617887
TI  - Parameters affect orthodontic treatment.

PMID- 16617889
TI  - Looking for volunteers. With the number of uninsured on the rise, the proportion
      of physicians willing to provide free care is on the decline.
AB  - Even as the number of the uninsured has grown to 46 million, the percentage of
      doctors providing free care has dropped by 8 points since 1996-97. The increasing
      pressures on physicians are cited as among the reasons. "It's got to do with a
      lot of things going on with their practices--insurance costs, the reimbursement
      rate, high overhead", says Linda Kinney, left, of Project Access.

PMID- 16617890
TI  - Still in the cross hairs. Charity-care scrutiny continues to dog hospitals.

PMID- 16617891
TI  - Antitrust probe targets HRDI. Execs may be getting squeamish about investigation.

PMID- 16617893
TI  - Contrasts in cardiac care. Wide disparities found in patient mortality.

PMID- 16617892
TI  - Doctors make the difference. Physicians' costs are shown to vary widely: study.

PMID- 16617894
TI  - Mixed blessing. Centers welcome attention, but want more funding.

PMID- 16617895
TI  - Dealmaking will cool in 2006: report. Outside influences like elections, energy
      prices expected to slow mergers, acquisitions.

PMID- 16617896
TI  - CMS hands out big IT contracts. Consolidation aims to save money and boost
      security.

PMID- 16617897
TI  - Firm offers price reports.

PMID- 16617898
TI  - Building compromise in Minn. Hospital fight spurs talk of reviewing construction
      rules.

PMID- 16617899
TI  - Patient-lifting law OK'd. Wash. State adopts landmark safety legislation.

PMID- 16617900
TI  - Not as simple as black and white. Racism, patients, state laws at stake for Ind.
      hospital.

PMID- 16617901
TI  - CareFirst pares profits. Strategy aims to fulfill insurer's not-for-profit
      mission.

PMID- 16617902
TI  - Ore. hospital keeps status for now. Immediate jeopardy avoided, other issues
      still remain.

PMID- 16617903
TI  - Transparent motives. Hospitals caught between a Newt and a hard place on pricing.

PMID- 16617904
TI  - Health Care Hall of Fame. Spinning off success. Vernon Loucks helped mentor a
      cadre of future leaders at Baxter.

PMID- 16617905
TI  - Health Care Hall of Fame. The 'straight arrow'. D. Kirk Oglesby Jr. brought low
      key leadership to local and national stages.

PMID- 16617906
TI  - Health Care Hall of Fame. 'The best of both worlds'. C. Thomas Smith says
      hospital administration let him serve community.

PMID- 16617907
TI  - Investing in the next generation. ACHE looks to model importance of lifelong
      learning, integrity and diversity.

PMID- 16617908
TI  - ACHE Young Executive of the Year. Drawn to healthcare. Jones calls building
      relationships with medical staff key.

PMID- 16617909
TI  - ACHE Lifetime Service Award. 40 years of service. Pierce honored for career
      leading Canadian hospitals.

PMID- 16617910
TI  - Lower supply costs, higher quality. Working with your medical staff on physician
      preference items. Panel discussion.

PMID- 16617911
TI  - Measuring success. IT is key to transforming healthcare. Interview by Andis
      Robeznieks.

PMID- 16617912
TI  - Can a CRNA be medically directed and be an independent contractor for tax
      purposes at the same time?
AB  - Employee or independent contractor designation has significant tax implications
      for the Certified Registered Nurse Anesthetist (CRNA). On superficial view, it
      appears that a CRNA who is medically directed would be under a number of controls
      that would force the CRNA to be in an employee status. However, on analysis, it
      seems that for tax purposes a CRNA can be medically directed while also being an
      independent contractor. But when looking closer at all of the controversy in the
      legal system and the protections available to an employee that are not available
      to an independent contractor, a CRNA may find the employee status a better
      option.

PMID- 16617913
TI  - Is doctoral education in our future?

PMID- 16617914
TI  - Perioperative beta blockade in noncardiac surgery: a review of the literature.
AB  - Perioperative beta blockade has been proven to significantly reduce the incidence
      of myocardial ischemia and myocardial infarction and of long-term overall
      mortality related to cardiac events after various surgeries in patients at
      intermediate or high risk for such events. The major physiologic effects of beta
      blockers result in a positive balance of myocardial oxygen supply and demand.
      Although the optimal time frame for initiation of treatment is not clear from the
      available data, it has been shown that beta blocker therapy is effective when
      started at least 1 week before the scheduled surgery and continued throughout the
      postoperative period. The current recommendations for perioperative beta blockade
      for patients at intermediate and high risk for a perioperative cardiac event are
      to use a beta1 blocking agent, begin therapy several weeks before a planned
      operation, titrate the dose to achieve a heart rate of 60 to 70 beats per minute,
      and taper the dose of the beta blocker after the postoperative period.

PMID- 16617915
TI  - Pollution of ambient air by volatile anesthetics: a comparison of 4 anesthetic
      management techniques.
AB  - Long-term exposure to waste anesthetic gas (WAG) may lead to health problems. The
      purpose of this study was to compare WAG concentrations resulting from 4
      combinations of fresh gas flow (FGF) and vaporizer settings during a simulated
      intravenous induction in which the anesthetic is deepened using a volatile
      anesthetic delivered via mask ventilation before intubation. By using a lung
      model, WAG was sampled 3 times each using 4 combinations and 3 volatile
      anesthetics: 3% sevoflurane, 2% isoflurane, and 6% desflurane. The combinations
      were FGF off/vaporizer on, FGF on/vaporizer off, both on, and both off. WAG was
      measured using a MIRAN Ambient Air Analyzer placed at a level approximating the
      anesthetist's head. One-way analysis of variance with a Student-Newman-Keuls post
      hoc test was used to compare the concentration of WAG among the combinations of
      FGF/vaporizer settings for each agent. Regardless of the agent, only the FGF
      on/vaporizer on combination at 60 seconds resulted in a statistically greater WAG
      level (P < .005). The results support using 3 of the 4 combinations examined when
      mask ventilation with a volatile agent accompanies intravenous induction. Future
      studies should examine other methods of controlling WAG levels and use time
      weighted averages to help address clinical significance.

PMID- 16617916
TI  - The effect of transdermal scopolamine on the incidence and severity of
      postoperative nausea and vomiting in a group of high-risk patients given
      prophylactic intravenous ondansetron.
AB  - Specific risk factors place patients at greater risk for postoperative nausea and
      vomiting (PONV). Routinely, these patients are treated prophylactically with
      intravenous (IV) ondansetron or transdermal (TD) scopolamine. No study has
      examined what effect using a combination of these prophylactic treatments would
      have on the incidence of PONV in a group of high-risk patients. A total of 56
      patients at high risk for PONV were treated prophylactically with IV ondansetron
      and randomized to receive a TD scopolamine patch or placebo. Demographics,
      incidence, and severity of PONV and side effects and antiemetic requirements were
      measured. Nausea was measured using a 0 to 10 verbal numeric rating scale.
      Descriptive and inferential statistics were used for analysis. No difference in
      demographics or the incidence of side effects was noted between groups. Patients
      in the scopolamine group had a lower incidence of PONV (P = .043), longer time to
      first reported nausea (P = .044), longer time to first episode of emesis (P =
      .031), and decreased supplemental antiemetic requirements (P = .016) compared
      with the placebo group. Based on this study, we recommend using a combination of
      TD scopolamine and IV ondansetron to prevent PONV in patients identified as high
      risk for PONV.

PMID- 16617917
TI  - Anesthetic implications for patients receiving exogenous corticosteroids.
AB  - Opposing views exist about perioperative replacement of corticosteroids and
      appropriate replacement dosages. Anesthesia providers must be aware of the need
      for corticosteroid replacement not only in patients who have primary adrenal
      insufficiency but also in patients who have adrenal insufficiency resulting from
      long-term corticosteroid therapy. Without adequate knowledge, the anesthesia
      provider may fail to prepare the patient to withstand the stress of surgery and
      may open the way for life-threatening hemodynamic abnormalities that accompany
      inadequate amounts of corticosteroids. The purpose of this article is to review
      the literature explaining the rationale and the proper perioperative dosing with
      corticosteroids for patients with long-standing asthma, rheumatoid arthritis, or
      Crohn disease. The review of literature reflects articles on endogenous hormones,
      exogenous hormones, diseases that require long-term corticosteroid therapy, the
      hypothalamus-pituitary-adrenal axis, and corticosteroid replacement therapy.

PMID- 16617918
TI  - Thoracic endovascular stent graft placement: a case report.
AB  - Endovascular stent grafting (EVSG) is a minimally invasive alternative to open
      repair of thoracic aortic aneurysms. It is useful in the treatment of thoracic
      aneurysms, dissections, and ruptures. Currently, the incidence of thoracic aortic
      aneurysms is 6:100,000 people. Comorbidities often include hypertension, coronary
      artery disease, chronic obstructive pulmonary disease, peripheral vascular
      disease, and cerebrovascular disease, and there often is a history of smoking.
      Without surgical intervention, a high risk of mortality exists, primarily due to
      aneurysm rupture. Due to the complexity of performing open surgical repair of the
      thoracic aorta and its associated morbidities such as paraplegia, renal failure,
      stroke, and prolonged ventilator support, new approaches to thoracic aneurysm
      repair are being investigated. When compared with open repair, stent grafting is
      a palliative rather than a curative treatment, and the risk of aneurysmal rupture
      still exists. This article describes a patient who underwent EVSG who had a
      history of abdominal aortic aneurysm repair and a known bovine arch.

PMID- 16617919
TI  - The neurobiology of the human febrile response.
AB  - Fever is a normal adaptation in response to a pyrogenic stimulus resulting in the
      generation of cytokines and prostaglandins. Fever differs from hyperpyrexia and
      hyperthermia associated with hot environs and pharmacological triggers.
      Typically, pyrogens are infectious organisms or their direct products (toxins).
      The body produces a wide array of pyrogenic cytokines such as interleukins (IL-1,
      IL-6), interferon, and tumor necrosis factor. Tissue trauma can trigger the
      febrile response, as can infectious organisms, certain medications, and blood
      products. The circumventricular organ system (CVOS) is neuronal tissues lying
      outside the blood-brain barrier that has a key role in initiating the
      communication sequence responsible for the synthesis of febrile prostaglandins.
      When pyrogenic cytokines are detected by the CVOS, prostaglandin synthesis,
      especially cyclooxygenase-dependent prostaglandin E2, is induced, activating the
      febrile response. Once the appropriate signal is received by the hypothalamus,
      autonomic, endocrine, and behavioral processes are activated until the
      hypothalamic set-point is reset downward as a consequence of a reduction in
      pyrogen content or antipyretic therapy, with subsequent heat loss. There is
      little evidence that fever facilitates recovery from disease or assists the
      immune system in mounting a response. Antipyretics are used commonly to decrease
      the distressing manifestations associated with fever.

PMID- 16617920
TI  - JCAHO, unannounced: just-surveyed organizations share compliance tips.

PMID- 16617921
TI  - Watch for these changes during 2006 surveys.

PMID- 16617922
TI  - Discharge planning advisor. Letting go of the 'that's not how we do it here'
      mindset.

PMID- 16617923
TI  - Are improvements getting lost in committees?

PMID- 16617925
TI  - Survey is rigorous, but staff get morale boost.

PMID- 16617924
TI  - Too exhausted to act safely?

PMID- 16617926
TI  - Health characteristics of adults 55 years of age and over: United States, 2000
      2003.
AB  - OBJECTIVE: This report highlights the health characteristics of four age groups
      of older adults-55-64 years, 65-74 years, 75-84 years, and 85 years and over
      providing estimates by sex, race and Hispanic origin, poverty status, health
      insurance status, and marital status. METHODS: The estimates in this report were
      derived from the 2000-2003--National Health Interview Surveys' Family and Sample
      Adult questionnaires. Estimates are based on interviews with 39,990 sample adults
      aged 55 years and over. RESULTS: Overall, prevalence rates for fair or poor
      health, chronic health conditions (with the exception of diabetes), sensory
      impairments, and difficulties with physical and social activities increased with
      advancing age, doubling or even tripling between the age groups 55-64 and 85
      years and over. About one in five adults aged 55-64 years were in fair or poor
      health, rising to about one-third of adults aged 85 years and over. Men and women
      were about equally likely to be in fair or poor health across the age groups
      studied, but women were more likely to have difficulty in physical or social
      activities. Sociodemographic variations in health were noted across the age
      groups studied, with the most consistent and striking results found for poverty
      status and health insurance coverage. Poor and near poor adults and those with
      public health insurance were, by far, the most disadvantaged groups of older
      adults in terms of health status, health care utilization, and health behaviors.
      CONCLUSIONS: Health status, health care utilization, and health-promoting
      behaviors among adults aged 55 and over vary considerably by age and other
      sociodemographic characteristics. Identifying these variations can help
      government and private agencies pinpoint areas of greatest need and greatest
      opportunity for extending years of healthy life among the Nation's seniors.

PMID- 16617927
TI  - HIV therapy, guided by CD4 counts.

PMID- 16617928
TI  - The older patient with HIV infection.

PMID- 16617929
TI  - Kaposi sarcoma of the larynx.

PMID- 16617930
TI  - Immune reconstitution inflammatory syndromes: what's new?
AB  - The immune reconstitution inflammatory syndrome (IRIS) is characterized by
      worsening clinical, laboratory, or radiologic findings despite improvements in
      the HIV RNA level and CD4 count after the introduction of antiretroviral therapy
      and is due to the restoration of pathogen-specific immune responses. IRIS may
      occur during or shortly after the treatment of an opportunistic infection or as a
      "new" clinical syndrome resulting from a previously unrecognized occult
      infection. Risk factors for IRIS include a low CD4 count, the presence of latent
      infection(s), and a robust virologic and immunologic response to HAART. In
      addition to infectious pathogens, IRIS is associated with autoimmune or
      malignancy-related conditions. Given the increasing availability of HAART, the
      number and types of IRIS encountered by HIV care providers will also increase.
      The prognosis for most IRIS cases is favorable because a robust inflammatory
      response may predict an excellent response to HAART in terms of immune
      reconstitution and, perhaps, improved survival. This article summarizes the
      various clinical presentations of IRIS and discusses the diagnosis and treatment
      of these immune-related syndromes.

PMID- 16617931
TI  - Tenofovir for chronic hepatitis B virus infection in HIV-coinfected patients.
AB  - Tenofovir has significant activity against hepatitis B virus (HBV), but clinical
      data about its utility for treatment of hepatitis B in patients coinfected with
      HBV and HIV are limited. We report the long-term safety and efficacy of tenofovir
      in 6 HBV-HIV-coinfected persons who received tenofovir as part of their
      antiretroviral regimen and were followed up for an average of 26.8 months (range,
      19 to 33 months). Four of 6 patients were positive for hepatitis B e antigen
      (HBeAg), and all 6 had initial HBV DNA levels greater than 7 log10 copies/mL. HBV
      DNA levels dropped by a mean (median) of 2.83 (3.40) and 3.92 (4.63) log10 after
      12 and 24 months of treatment, respectively. After 24 months, 3 patients had HBV
      DNA levels below the limit of detection and 5 had HIV RNA levels below the limit
      of detection (less than 400 copies/mL). The sixth patient had stopped treatment
      and had a 0.14-log10 decrease in HIV RNA level at 36 months of follow-up. The
      CD4+ lymphocyte count increased by a mean (median) value of 47/microL
      (177/microL). No significant adverse events attributable to tenofovir therapy
      were reported.

PMID- 16617932
TI  - Primary vitamin D deficiency in adults.
AB  - In adults, prolonged deficiency of vitamin D (calciferol) can lead to
      osteomalacia, while lesser deficiency (insufficiency) is associated with various
      non-specific symptoms. Both vitamin D deficiency and insufficiency are becoming
      more common in developed countries. In the UK, the prevalence of vitamin D
      deficiency in all adults is around 14.5%, and may be more than 30% in those over
      65 years old and as high as 94% in otherwise healthy south Asian adults. By
      comparison, the prevalence of vitamin D insufficiency in adults may be as high as
      55%, and the condition is even more common in patients with osteoporotic
      fractures. Recently, we discussed the management of children with primary vitamin
      D deficiency. Here we review the management of adults with the condition.

PMID- 16617933
TI  - Strontium ranelate for osteoporosis?
AB  - In the UK, there are around 200,000 osteoporotic fractures each year. National
      guidelines in the UK recommend preventative treatment in patients who are at high
      risk of fracture on the basis of age, fracture history, bone mineral density and
      other risk factors. For secondary prevention, an oral bisphosphonate, such as
      alendronate or risedronate, is the drug of choice but may not be tolerated,
      particularly because of unwanted upper gastrointestinal effects. Raloxifene
      provides a potential oral alternative in women. National guidelines also suggest
      subcutaneous teriparatide for women aged more than 65 years with severe
      osteoporosis who have failed to tolerate or respond to a bisphosphonate; however,
      we believe use of this drug is problematic. Strontium ranelate (Protelos-Servier)
      is a new oral treatment for women with postmenopausal osteoporosis that is
      promoted as "the first dual action bone agent" and "the only drug to
      simultaneously increase bone formation and decrease bone resorption". Here we
      review the evidence for strontium ranelate and consider whether it has a role in
      postmenopausal osteoporosis.

PMID- 16617934
TI  - Treatment of third molar teeth--assessment.

PMID- 16617935
TI  - Meeting the Dental Council President.

PMID- 16617936
TI  - The land of a 1,000 welcomes.

PMID- 16617937
TI  - Treatment of third molar teeth--surgery.
AB  - The indications for removal of third molar teeth along with the pre-operative
      assessment of the patient have been outlined. This article reviews the surgical
      options and identifies the possible post-operative sequelae and potential
      complications of treatment.

PMID- 16617938
TI  - Tooth brushing, tooth wear and dentine hypersensitivity--are they associated?
AB  - Evidence suggests that patients suffer the painful symptoms of dentine
      hypersensitivity when dentine is exposed and the dentinal tubule system is opened
      to the oral cavity to allow stimuli to trigger a neural response in the pulp via
      a hydrodynamic mechanism. The processes needed to localise lesions of dentine
      hypersensitivity include loss of enamel and/or gingival recession. Whilst tooth
      brushing with or without toothpaste appears to cause minimal wear to enamel (in
      the absence of acids), circumstantial evidence implicates tooth brushing with
      gingival recession and exposure of dentine. Other tooth wear processes, notably
      attrition and acid erosion, cause loss of enamel and can expose dentine.
      Therefore, sensitivity may result. How lesions of dentine hypersensitivity are
      initiated is a matter of conjecture and based on extrapolating data from studies,
      mainly in vitro, to effect in vivo. Again, this circumstantial type of evidence
      suggests that abrasion by some toothpastes and erosion by dietary acid could open
      the tubule system. Little is known about the actual effect of de-sensitising
      toothpastes on lesions of dentine hypersensitivity even though they are
      formulated to either occlude dentinal tubules or block the neural response in the
      pulp. Clinical studies have produced contradictory findings for the efficacy of
      products and there have been extremely few evidence-based reviews. In conclusion,
      available evidence supports a probable link of tooth brushing, with or without
      toothpaste and an acidic diet, to both tooth wear and dentine hypersensitivity,
      and also suggests that dentine hypersensitivity is a tooth wear phenomenon.
      Although there is a need for more direct clinical and scientific evidence for
      these associations, it is recommended that they be taken into consideration when
      planning management strategies for the dentine hypersensitivity sufferer.

PMID- 16617939
TI  - Antibiotic prophylaxis for bacterial endocarditis--a study of knowledge and
      application of guidelines among dentists and cardiologists.
AB  - Antibiotic prophylaxis and infective endocarditis is a controversial topic. The
      compliance with available guidelines among dentists is poor. The dental health
      education of patients by their cardiologists is inadequate. OBJECTIVE: The
      objective of this study was to investigate the knowledge and application of
      available guidelines on antibiotic prophylaxis to prevent infective endocarditis
      among general dental practitioners and cardiologists. DESIGN: Structured postal
      questionnaire SUBJECTS AND METHODS: A list of 515 dentists was obtained from a
      register held by the Postgraduate Medical and Dental Board. A list of 85
      cardiologists was obtained from a national register held by the Cardiothoracic
      Society of Ireland. RESULTS: A 31% response rate was obtained from the
      cardiologists and 37% from the dentists. The majority of the cardiologists (84%)
      were in hospital practice and 64% of dentists were in private general practice.
      Cardiologists showed a preference for the AHA guidelines (50%) and more dentists
      use the BSAC guidelines (56%). The cardiologists were very familiar with the
      cardiac conditions that pose a risk for dental patients but weak at educating
      their patients on the importance of good dental health. The dentists were good at
      identifying procedures that could place their patients at risk but less informed
      about which cardiac conditions warranted prophylaxis. Decision-making among the
      dentists with regard to choice of prophylaxis and appropriate treatment intervals
      was poor. CONCLUSIONS: The knowledge of and compliance with the available
      guidelines is poor. Dental health education of at-risk patients by their
      cardiologists and dentists is inadequate. Further regular education of patients,
      dentists and medical practitioners is required.

PMID- 16617941
TI  - Marketing and image.

PMID- 16617940
TI  - Dismissals--procedures and pitfalls.

PMID- 16617942
TI  - Solitary bone cyst.

PMID- 16617943
TI  - A web-based tool for the Comprehensive Unit-based Safety Program (CUSP).
AB  - BACKGROUND: An organization's ability to change is driven by its culture, which
      in turn has a significant impact on safety. The six-step Comprehensive Unit-Based
      Safety Program (CUSP) is intended to improve local culture and safety. A Web
      based project management tool for CUSP was developed and then pilot tested at two
      hospitals. HOW ECUSP WORKS: Once a patient safety concern is identified (step 3),
      a unit-level interdisciplinary safety committee determines issue criticality and
      starts up the projects (step 4), which are managed using project management tools
      within eCUSP (step 5). On a project's completion, the results are disseminated
      through a shared story (step 6). CASE STUDIES: OSF St. Joseph's Medical Center
      The Medical Birthing Center (Bloomington, Illinois), identified 11 safety issues,
      implemented 11 projects, and created 9 shared stories--including one for its
      Armband Project. The Johns Hopkins Hospital (Baltimore) Medical Progressive Care
      (MPC4) Unit identified 5 safety issues and implemented 4 ongoing projects,
      including the intravenous (IV) Tubing Compliance Project. DISCUSSION: The eCUSP
      tool's success depends on an organizational commitment to creating a culture of
      safety.

PMID- 16617944
TI  - Actions and implementation strategies to reduce suicidal events in the Veterans
      Health Administration.
AB  - BACKGROUND: Veterans possess many risk factors for suicide, making suicide
      prevention in the Veterans Health Administration (VHA) a particular challenge.
      METHODS: An analysis was conducted of 94 aggregated root cause analyses (RCAs)
      for parasuicidal behavior and 43 single-case suicide RCAs submitted from 75 VHA
      facilities to determine primary root causes for suicide and parasuicidal
      behaviors and to gain information about action plans, success factors and
      obstacles to improvement. Telephone follow-up interviews were conducted with each
      facility. RESULTS: The aggregate reviews included 775 individual cases of
      parasuicidal behavior. The top root causes of parasuicidal behavior were poor
      assessment and communication of patient risk, patient stressors, and need for
      staff and patients training. Forty-eight percent of the action plans developed to
      address the root causes involved a policy change, 30% involved staff training,
      and 14% involved making a specific clinical change. Eight-eight percent of the
      actions adequately addressed the root cause, of which 68.1% were fully
      implemented. DISCUSSION: There is little agreement on the definition of
      "parasuicide," and it is likely the case that parasuicide behaviors are
      underreported in our system. To encourage reporting, patient safety staff should
      collaborate with providers and use a more inclusive definition of parasuicide.

PMID- 16617945
TI  - Sustained improvement for specialty clinic access.
AB  - BACKGROUND: Veterans Affairs New Jersey Health Care System (VA NJHCS) used the
      advanced clinic access (ACA) strategies and applied "facility communication
      model" principles to improve access to care at two medical centers and a
      community-based outpatient clinic. Implementation of the facility model included
      the integration of a performance improvement (PI) structure, use of the
      technology, and staff participation. METHODS: VA NJHCS participated in a Veterans
      Integrated Service Network (VISN 3) collaborative consisting of five network
      facilities from June 2001 to January 2002. Specialty clinics were to develop the
      capacity to schedule a specialty clinic appointment in less than 30 days. ACA
      strategies were as follows: reduction of appointment types, reduction of demand,
      development of service agreement with primary care, and standardized
      documentation using templates. RESULTS: The VA NJHCS average waiting time for a
      next-available urology clinic appointment decreased 85.9%, versus a 26.2%
      reduction in the Veterans Health Administration (VHA) national average. In June
      2005, the average days waiting time for a next-available urology clinic
      appointment at VA NJHCS was 14.2 days, or 24.6 days (63.4%) better than the VHA
      average of 38.8 days. DISCUSSION: Waiting time reduction for urology clinic
      appointments at VA NJHCS is similar to results reported elsewhere using the
      collaborative model and ACA strategies. Yet, the added dimension of a facility
      model resulted in a waiting time reduction for urology clinics at VA NJHCS that
      exceeded the VHA national average.

PMID- 16617946
TI  - When implementation fails: the case of a nursing guideline for fall prevention.
AB  - BACKGROUND: Implementing guidelines can be very difficult. No magic bullet or
      step-by-step implementation plan is available, neither is any single
      implementation strategy superior. At the Academic Medical Center (AMC) in
      Amsterdam, a nursing guideline was developed in 1993 on prevention of patient
      falls. Falls decreased by 30% on six wards, yet an effort to implement the
      guideline into daily practice throughout the hospital failed. A renewed effort
      was made to implement the guideline in two wards (neurology and internal
      medicine) in 1999. IMPLEMENTING THE GUIDELINE: Preparations were made for
      implementation in the two wards. Barriers to change were identified and solutions
      were translated into day-to-day activities in the wards. The intervention period
      covered 18 months (January 2000-June 2001). A mix of implementation strategies
      was used, including a local consensus process, educational activities, and active
      support and feedback to management and staff. RESULTS: In the internal medicine
      ward, the target incidence of 6% was met for four of the 18 months in the
      intervention period. In the neurology ward, the incidence target of 11% was met
      in five months. DISCUSSION: Barriers to change and enabling factors may only
      become apparent during the implementation process itself. A strongly perceived
      need to change daily practice, a simple guideline, the hospital board's support,
      an understanding of local barriers, monitoring of outcomes, a locally tailored
      multifaceted implementation strategy, and voluntarily cooperating nurses are no
      guarantees for success.

PMID- 16617947
TI  - Using Failure Mode and Effects Analysis for safe administration of chemotherapy
      to hospitalized children with cancer.
AB  - BACKGROUND: The administration of chemotherapy to hospitalized children with
      cancer is a complex and high-risk process. A team divided the process into three
      areas--prescribing, dispensing, and administration--and used Failure Mode and
      Effects Analysis (FMEA) to identify the elements of risk and implement
      appropriate strategies. For each area, potential failures within subprocesses
      were assigned risk priority numbers (RPNs), reflecting their frequency, severity,
      and detectability. STRATEGIES FOR RISK REDUCTION: The team made prescribing and
      administration, the areas with the highest RPNs, the focus of most of its
      strategies, which were introduced and completed in 2002. POSTIMPLEMENTATION
      RESULTS: The potential prescribing error rate decreased from 23% to 14%; use of
      preprinted standard order sets increased from 22% to 45% in 2003 (one year after
      the FMEA was conducted) and 76% in 2005. Actual dispensing errors decreased from
      3 to 1, and the actual administration errors from 4 to 3. FINAL REFLECTIONS:
      Computerized order entry systems would only affect prescribing, dispensing, and
      administering, which would still be done manually, resulting in potential for
      failure. The FMEA project will be an ongoing part of providing safe chemotherapy
      treatments.

PMID- 16617948
TI  - SBAR: a shared mental model for improving communication between clinicians.
AB  - BACKGROUND: The importance of sharing a common mental model in communication
      prompted efforts to spread the use of the SBAR (Situation, Background,
      Assessment, and Recommendation) tool at OSF St. Joseph Medical Center,
      Bloomington, Illinois. CASE STUDY: An elderly patient was on warfarin sodium
      (Coumadin) 2.5 mg daily. The nurse received a call from the lab regarding an
      elevated international normalized ratio (INR) but did not write down the results
      (she was providing care to another patient). On the basis of the previous lab
      cumulative summary, the physician increased the warfarin dose for the patient; a
      dangerously high INR resulted. ACTIONS TAKEN: The medical center initiated a
      collaborative to implement the use of the SBAR communication tool. Education was
      incorporated into team resource management training and general orientation.
      Tools included SBAR pocket cards for clinicians and laminated SBAR "cheat sheets"
      posted at each phone. SBAR became the communication methodology from leadership
      to the microsystem in all forms of reporting. DISCUSSION: Staff adapted quickly
      to the use of SBAR, although hesitancy was noted in providing the
      "recommendation" to physicians. Medical staff were encouraged to listen for the
      SBAR components and encourage staff to share their recommendation if not
      initially provided.

PMID- 16617949
TI  - Faith, hope and recovery.

PMID- 16617950
TI  - Positively Scottish.

PMID- 16617951
TI  - Moving to inclusion.

PMID- 16617952
TI  - Can institutional psychiatry ever be reformed or is it too tied to capitalism?

PMID- 16617953
TI  - The challenge is to develop a truly multi-faith approach, not plural
      monofaithism.

PMID- 16617954
TI  - We were all so confident prospective employers would be falling over each other.

PMID- 16617955
TI  - If we want to know how best to help young people who self-harm, we should be
      asking the experts. Questions and answers.

PMID- 16617956
TI  - Limiting the damage.

PMID- 16617957
TI  - Tackling stigma in schools.

PMID- 16617958
TI  - Woman on the verge.

PMID- 16617959
TI  - Service users must keep on asking the really embarrassing questions.

PMID- 16617960
TI  - School nurses key to health plans.

PMID- 16617961
TI  - There have to be limits on bowing to patient convenience.

PMID- 16617962
TI  - Value-added nursing.

PMID- 16617963
TI  - Lymphoma legacy.

PMID- 16617964
TI  - The Essence of Care benchmark for patient health promotion.
AB  - A new benchmark for health promotion has been added to Essence of Care, the
      government strategy to improve the quality of the fundamental aspects of nursing
      care. The benchmark provides a tool for making health promotion part of everyday
      practice and is designed to be applicable to any area.

PMID- 16617965
TI  - Chronic fatigue syndrome.

PMID- 16617966
TI  - Homeostasis, part 1: anatomy and physiology.

PMID- 16617967
TI  - Methods of meeting patients' cancer information needs.
AB  - It is difficult to imagine the impact of a diagnosis of cancer. However, even
      where a patient has a poor prognosis, it is important to allow patients and their
      carers to set the information agenda. Cancer information specialists will be
      irreplaceable in helping to determine what information a patient needs, in what
      format and at what time, and how those needs change during the cancer journey.

PMID- 16617968
TI  - Temazepam.

PMID- 16617969
TI  - A workshop to maintain residents' mobility and activity.
AB  - Care homes have poor access to physiotherapy and occupational therapy, and
      consequently staff can be unaware of basic rehabilitation techniques. A workshop
      was devised to enable staff to learn simple strategies to improve and maintain
      residents' mobility and activity. This article describes its design, content and
      delivery.

PMID- 16617970
TI  - Enhancing support for nursing students in the clinical setting.
AB  - Quality clinical placement experiences are essential for effective student
      learning. Key factors that can influence this experience are students not feeling
      welcome in the clinical setting and limited opportunities for them to engage in
      learning. From a review of the literature and of personal experiences, this paper
      presents some guidelines that can be introduced at local level without requiring
      additional resources in order to improve students' experiences.

PMID- 16617971
TI  - How a flexible approach can make retirement easier.

PMID- 16617972
TI  - It might have been easier to absorb the NHS 'overspend' if we weren't still
      occupying Iraq.

PMID- 16617973
TI  - Campylobacter in poultry: filling an ecological niche.
AB  - Epidemiological studies indicate that Campylobacter species may be responsible
      for the majority of cases of sporadic gastroenteritis in humans. These studies
      also suggest that poultry may be one of the most common sources of the bacteria
      for humans. Campylobacter and related genera in the family Campylobacteraceae are
      oral and intestinal commensals of vertebrates and some nonvertebrates, a
      characteristic that complicates rational approaches to controlling Campylobacter
      contamination of poultry. This review will discuss the phylogeny, genomics, and
      physiology of campylobacters with the intention of revealing how these organisms
      have evolved to fill their intestinal ecological niche in poultry and how their
      physiology must be understood in order to enact effective control strategies.

PMID- 16617974
TI  - Campylobacter jejuni strains of human and chicken origin are invasive in chickens
      after oral challenge.
AB  - The aim of the study was to evaluate the colonizing ability and the invasive
      capacity of selected Campylobacter jejuni strains of importance for the
      epidemiology of C jejuni in Danish broiler chickens. Four C. jejuni strains were
      selected for experimental colonization studies in day-old and 14-day-old chickens
      hatched from specific pathogen free (SPF) eggs. Of the four C. jejuni strains
      tested, three were Penner heat-stable serotype 2, flaA type 1/1, the most common
      type found among broilers and human cases in Denmark. The fourth strain was
      Penner heat-stable serotype 19, which has been shown to be associated with the
      Guillain Barre Syndrome (GBS) in humans. The minimum dose for establishing
      colonization in the day-old chickens was approximately 2 cfu, whereas two- to
      threefold higher doses were required for establishing colonization in the 14-day
      old chickens. Two of the C. jejuni strains were shown to be invasive in orally
      challenged chickens as well as in three different human epithelial cell lines.

PMID- 16617975
TI  - Antigenic and genetic characterization of an avian poxvirus isolated from an
      endangered Hawaiian goose (Branta sandvicensis).
AB  - An avian poxvirus from cutaneous lesions in a Hawaiian goose (Branta
      sandvicensis) was characterized in this study. The virus was isolated by
      inoculation onto the chorioallantoic membranes (CAMs) of developing chicken
      embryos. Cytoplasmic inclusion bodies were observed on histopathological
      examination of CAM lesions. Western blotting analysis using polyclonal antiserum
      against fowl poxvirus (FWPV) showed differences from FWPV, but a similar
      antigenic profile between Hawaiian goosepox (HGP) isolate and two previous
      Hawaiian poxvirus isolates were observed. Still three avian poxviruses from
      Hawaiian birds showed distinguishable reaction in approximately 27, 34, 35, and
      81 kDa proteins when polyclonal antibodies against the Hawaiian poxvirus isolate
      (Alala/lanakila) were used. Restriction fragment length polymorphisms (RFLP) of
      DNA of this isolate also showed differences from those of FWPV and previous
      avianpox isolates from Hawaiian forest birds. While nucleotide sequences of a 5.3
      kb PstI-HindIII fragment of the genome of HGP isolate revealed very high homology
      (99% identities) with Canary poxvirus (CNPV) ORF266-274, and like CNPV, homologs
      of three FWPV ORFs (199, 200, and 202) including any reticuloendotheliosis virus
      (REV) sequences are not present in the genome of HGP isolate.

PMID- 16617976
TI  - Identification of new morphological and life-cycle stages of Cochlosoma anatis
      and experimental transmission using pseudocyst.
AB  - Cochlosoma anatis is a flagellated intestinal parasite that infects a variety of
      avian species. C. anatis infections have been associated with decreased weight
      gain and increased morbidity and mortality. Conditions favoring the growth of
      this organism in birds are current pathogenic intestinal infections and/or young
      age. There is little data describing the life cycle of this parasite. In this
      study, electron microscopy images are presented that document longitudinal binary
      fission of the trophozoite stage and outline the events of pseudocyst formation,
      which includes a rounding stage. Evidence provided here indicates that the
      pseudocyst stage may be a mechanism for transmission of this organism. The
      observations reported here provide additional evidence of homology between
      Cochlosoma and members of the trichomonad order.

PMID- 16617977
TI  - Differentiation of infectious laryngotracheitis virus isolates by restriction
      fragment length polymorphic analysis of polymerase chain reaction products
      amplified from multiple genes.
AB  - Infectious laryngotracheitis (ILT) has been identified in most countries around
      the world and remains a threat to the intensive poultry industry. Outbreaks of
      mild to moderate forms of ILT are common in commercial layer flocks, while
      sporadic outbreaks of ILT in broiler flocks have also been recognized as an
      emerging problem in several countries. Examination of viral isolates using
      restriction fragment length polymorphism of polymerase chain reaction (PCR-RFLP)
      from individual ILTV genes has suggested that some of these outbreaks were caused
      by vaccine strains. In this study, PCR-RFLP of a number of ILTV genes/genomic
      regions including gE, gG, TK, ICP4, ICP18.5, and open reading frame (ORF) B-TK
      was used to examine a number of historical and contemporary Australian ILTV
      isolates and vaccine strains. PCR-RFLP of gE using restriction endonuclease EaeI
      failed to distinguish between any of the isolates including the vaccine strains.
      PCR-RFLP of gG, TK, and ORFB-TK using restriction endonucleases MspI and FokI,
      respectively, divided all the isolates into two groups. PCR-RFLP of ICP18.5 and
      ICP4 using restriction endonuclease HaeIII separated the isolates into three
      different groups with some field isolates only able to be distinguished from
      vaccine strains by PCR-RFLP of ICP18.5. A combination of groupings including gG,
      TK, ICP4, ICP18.5, and ORFB-TK PCR-RFLP classified the ILTV isolates under
      investigation into five different groups with most isolates distinguishable from
      vaccine strains. Results from this study reveal that to achieve reliable
      identification of strains of ILTV, the examination of multiple gene regions will
      be required, and that most of the recent ILT outbreaks in Australia are not being
      caused by vaccine strains.

PMID- 16617978
TI  - Detection of Histomonas meleagridis DNA in different organs after natural and
      experimental infections of meat turkeys.
AB  - Histomonas meleagridis infection of turkeys is usually accompanied by a severe
      disease with unspecific clinical symptoms but with distinct pathological lesions
      in the ceca and liver. In the literature some macro- and microscopic evidence of
      the spread of histomonads to the other organs has been provided. The aim of the
      present investigations was to use real-time polymerase chain reaction (PCR) to
      demonstrate the dissemination of H. meleagridis DNA to different organs after
      natural and experimental infection of meat turkeys. Samples from several organs
      were collected from a meat-turkey flock, which proved to be naturally infected
      with histomoniasis, and examined for histomonad DNA by real-time PCR. Histomonad
      DNA was detected in all investigated ceca, livers, spleens, kidneys, and pooled
      brain swabs. Additionally it was found in 75% of investigated samples from bursae
      of Fabricius, in 50% of investigated duodenums, and in 40% of investigated
      jejunum samples. After experimental intracloacal infection of 3-wk-old turkey
      poults with 147,500 histomonads, similar samples were collected from all turkeys
      that died. After a 3-wk observation period the surviving birds, as well as the
      noninfected control group, were euthanatized and samples were taken. During the
      entire experimental period, 10 birds out the 20 infected birds died. Histomonad
      DNA was detected in all investigated ceca, livers, lungs, and hearts (100%) and
      almost all kidneys (90%) and bursae of Fabricius (80%). On the other hand, only
      30% of examined spleens and 10% of brain samples revealed positive results.
      Surviving infected birds were euthanatized and necropsied; histomonad DNA was
      found in one out of 10 livers but not in any ceca. Also, histomonad DNA could not
      be detected in examined cecal and lung samples from the noninfected control
      group.

PMID- 16617980
TI  - Ocular responses to ammonia in broiler chickens.
AB  - In two trials, 60 male commercial broilers were placed in each of eight
      environmentally controlled chambers receiving 0, 25, 50, or 75 ppm aerial ammonia
      from 1 to 28 days. Birds exposed to 25 ppm (lower concentration) ammonia gas
      developed ocular abnormalities but at a slower rate when compared with birds
      exposed to 50 and 75 ppm (higher concentrations). Birds exposed to higher
      concentrations also developed more severe lesions. With little atmospheric
      ammonia present after 28 days of the grow-out stage, the corneas indicated signs
      of healing. Lymphocytes and heterophils were seen in the iris at 49 days in
      ammonia-exposed birds even when ammonia exposure was terminated at 28 days. The
      lower ammonia concentrations resulted in abnormalities that were slight when
      compared with those seen at the higher ammonia concentrations. As measured by the
      incidence of inflammatory infiltrates in the trachea, lung, and air sacs,
      respiratory tract tissues did not appear to be affected by any tested level of
      aerial ammonia. The findings in this investigation represent the first report
      indicating that ammonia-induced uveitis in chickens clears rapidly after exposure
      to ammonia ceases.

PMID- 16617979
TI  - Characterization of experimental Mycoplasma gallisepticum infection in captive
      house finch flocks.
AB  - The use of controlled, horizontal-transmission experiments provides detailed
      information on the spread of disease within fixed social groups, which informs
      our understanding of disease dynamics both in an empirical and theoretical
      context. For that reason, we characterized in 2002, horizontal transmission of
      Mycoplasma gallisepticum (MG) in two flocks of 11 wild-caught house finches
      housed in outdoor aviaries over a 6-mo period. All birds were initially free of
      MG by a polymerase chain reaction (PCR)-based test, rapid plate agglutination
      (RPA), and the scoring of physical signs. We inoculated one flock member
      bilaterally in the palpebral conjunctiva and reintroduced it into its cage. Index
      birds developed conjunctivitis within 3 to 5 days but died 13 and 20 days
      postinfection (PI) possibly because of very severe weather. The proportion of
      birds with physical signs increased gradually, reached 40% at 6 wk PI, and
      fluctuated around 40% until 21 wk PI. By the time our experiment ended at 24.5 wk
      PI, 28% of the birds still exhibited physical signs. Across both flocks, 80% of
      the birds developed unilateral or bilateral conjunctivitis, and several birds
      relapsed. The appearance of physical signs in new individuals occurred between 10
      and 144 days PI (median 41 days PI). Physical signs lasted 1-172 days (median 42
      days). Birds that became infected earlier during the experiment developed more
      severe conjunctivitis, and there was a tendency for birds that developed
      bilateral conjunctivitis to develop physical signs earlier. Most birds that
      developed physical signs of MG were also PCR- and RPA-positive, although we
      detected a single asymptomatic carrier and a single symptomatic false negative.
      No birds died as a result of secondary MG infection.

PMID- 16617981
TI  - Evaluation of the efficacy of a live fowlpox-vectored infectious
      laryngotracheitis/avian encephalomyelitis vaccine against ILT viral challenge.
AB  - Infectious laryngotracheitis (ILT) is caused by an alphaherpesvirus, and latency
      can be produced by previous exposure to vaccine virus. The main sites of latency
      for the ILT virus have been shown to be the trigeminal ganglion and the trachea.
      Reactivation of latent virus is one factor related to the production of clinical
      signs. The development of a genetically engineered ILT vaccine has been suggested
      for many years as a tool to eliminate viral latency. Several approaches have been
      suggested. Included among them is the development of a thymidine kinase-deficient
      mutant or the insertion of ILT viral glycoproteins into a viral vector such as a
      poxvirus. A commercially available, live, fowlpox-vectored infectious
      laryngotracheitis + avian encephalomyelitis (FP-LT+AE) vaccine was used in field
      trials in leghorn pullet flocks and evaluated by tracheal challenge in a
      laboratory setting with the use of the National Veterinary Services Laboratory
      (Ames, IA) ILT challenge virus. Interference of the pigeon pox vaccine, which is
      often administered concurrently with fowlpox vaccine, was also evaluated when
      given in conjunction with the FP-LT+AE vaccine. Overall, the results indicate
      that the FP-LT+AE vaccine provides adequate protection against ILT viral
      challenge. Proper administration is essential. In one flock, inadequate
      protection was most likely a result of either poor vaccine administration or
      previous exposure to pox virus. In addition, the simultaneous administration of
      pigeon pox vaccine did not appear to interfere with protection against ILT viral
      challenge.

PMID- 16617982
TI  - Campylobacter jejuni infection in broiler chickens.
AB  - Day-old, straight-run broiler chickens were procured from a hatchery located in
      the Pacific Northwest. The chickens were subdivided individually into nine groups
      of 20 chickens. The chickens were tagged, housed in isolation chambers on wire,
      fed commercial broiler feed, and given water ad libitum. Three isolates of
      Campylobacter jejuni of poultry origin and one of human origin were tested in
      this study. Various C. jejuni cultures were inoculated into 9-day-old chickens by
      crop gavage. Four groups of 20 chickens were inoculated at a dose level of 0.5 ml
      of 1 x 10(2) colony-forming units (CFU)/ml. The other four groups were inoculated
      with 0.5 ml of 1 X 10(4) CFU/ml. One group of 20 chickens was kept as an
      uninoculated control group. Four randomly selected chickens from each of the
      inoculated and uninoculated groups were necropsied at 5, 12, and 19 days
      postinoculation (DPI). The C. jejuni was cultured and enumerated from a composite
      of the upper and midintestine and the cecum. Body weights of all chicken groups
      at 7 days of age and at 5, 12, and 19 DPI were measured and statistically
      analyzed. No significant differences were present in the mean body weights (MBWs)
      of 7-day-old, 5 DPI, and 12 DPI male and female broiler chickens inoculated with
      C. jejuni at both dose levels compared with uninoculated controls. Differences in
      MBWs of the male and female broilers at 19 DPI were observed in some of the
      groups. Results of the C. jejuni culture enumeration mean (CEM) of composite
      intestine samples at 5 DPI from all inoculated chicken groups, irrespective of
      the dose level, ranged from (2.5 +/- 5.0) x 10(2) to (2.8 +/- 4.8) x 10(5) CFU/g
      (mean +/- SD). Results of cecum C. jejuni CEM at 5 DPI inoculated at both dose
      levels ranged from (2.5 +/- 5.0) x 10(6) to (1 +/- 0.0) x 10(7) CFU/g in all
      treatment groups irrespective of the dose level. CEM results from the composite
      intestine samples at 12 and 19 DPI increased by 1 log unit, or sometimes more.
      Results of cecum C. jejuni CEM at 5 DPI inoculated at both dose levels ranged
      from (2.5 +/- 5.0) x 10(6) to (1 +/- 0.0) x 10(7) CFU/g in all treatment groups
      irrespective of the dose level. Increases of 2-5 log units in C. jejuni CEM was
      present in chicken groups inoculated with 1 X 10(2) CFU of C. jejuni, and a 2- to
      3-log increase was present in groups inoculated with a higher dose level of C.
      jejuni at 12 DPI. The results of C. jejuni CEM from cecal samples at 19 DPI were
      similar to chicken groups at 12 DPI. Campylobacterjejuni was not isolated from
      the uninoculated control chickens at 5, 12, and 19 DPI. Clinical signs of illness
      or gross pathologic lesions were not present in any of the chicken groups during
      this study. No lesions were present on histopathologic evaluations in C. jejuni
      inoculated chickens or uninoculated control chickens.

PMID- 16617983
TI  - Baculovirus-mediated gene expression in chicken primary cells.
AB  - A recombinant baculovirus was constructed containing an expression cassette with
      a reporter gene, green fluorescent protein, directed by a constitutive mammalian
      promoter: a human cytomegalovirus immediate early promoter/enhancer (CMV-IE).
      High titer virus was prepared with ultracentrifugation. Efficient gene delivery
      and expression were observed in the virus-treated chicken primary culture,
      myoblast cells, and whole embryonic fibroblast cells. It was noticed that an
      addition of sodium butyrate (a selective histone deacetylase inhibitor) to viral
      transduction medium extremely enhanced the reporter-gene expression. However,
      there is no effect of presence of trichostatin A observed. To maximize the
      reporter-gene expression, the baculoviral infection condition was optimized with
      both cell types. Our approaches demonstrated that recombinant baculovirus could
      efficiently deliver its genome DNA into chicken primary cells and that CMV-IE, a
      mammalian-cell-active promoter, was functional in chicken primary cells and could
      direct a high level of gene expression. Clearly, the recombinant baculovirus
      provides an alternative means for foreign gene delivery into avian cells.

PMID- 16617984
TI  - Detection of genes encoding virulence factors and bacteriocins in fecal
      enterococci of poultry in Portugal.
AB  - Seventy-six Enterococcus isolates (43 E. faecalis, 30 E. faecium, two E. durans,
      and one E. hirae) recovered from fecal samples of poultry in a slaughterhouse
      (one isolate per fecal sample and one fecal sample per lot of animals) were
      studied for bacteriocin production and for the presence of genes encoding
      bacteriocins and virulence factors. The presence of genes encoding virulence
      factors (cpd, geE, fsr, ace, agg, and esp) and bacteriocins (entA, entB, entP,
      entQ, entAS-48, entL50A/B, cyl, and bac31) were studied by polymerase chain
      reaction in all enterococci. At least two virulence genes were detected in all 43
      E. faecalis isolates, cpd and gelE being the most frequently detected genes
      (97.7%) followed by ace (62.8%), agg (39.5%), fsr (27.9%), and esp (2.3%). No
      virulence genes were detected in the other enterococcal species with the
      exception of one E. faecium and one E. durans isolates that harbored the gelE
      gene. Antimicrobial activity against eight indicator bacteria (including Listeria
      monocytogenes) was assayed in the enterococci, and 23 (30.3%) showed inhibitory
      activity against L. monocytogenes, the other 22 enterococci showing activity
      against indicator bacteria other than L. monocytogenes. Only the entA, entB, and
      cyl genes were detected in our study (entA + entB in nine E. faecium isolates and
      the cyl gene in seven E. faecalis isolates). A wide variety of virulence genes
      have been detected in fecal E. faecalis isolates from poultry, but not in the
      other enterococcal species. However, the presence of known bacteriocin structural
      genes is associated more with the E. faecium species.

PMID- 16617985
TI  - Biological and molecular characterization of chicken anemia virus isolates from
      Slovenia.
AB  - The presence of chicken anemia virus (CAV) in Slovenia was confirmed by
      inoculation of 1-day-old chickens without antibodies against CAV and isolation of
      the virus on the Marek's disease chicken cell-MSB1 line and by polymerase chain
      reaction (PCR). Experimental inoculation of 1-day-old chickens resulted in lower
      hematocrit values, atrophy of the thymus, and atrophy of bone marrow. CAV was
      confirmed by PCR in the thymus, bone marrow, bursa of Fabricius, liver, spleen,
      ileocecal tonsils, duodenum, and proventriculus. The nucleotide sequence of the
      whole viral protein (VP)1 gene was determined by direct sequencing. Alignment of
      VP1 nucleotide sequences of Slovenian CAV isolates (CAV-69/00, CAV-469/01, and
      CAV-130/03) showed 99.4% to 99.9% homology. The VP1 nucleotide sequence alignment
      of Slovenian isolates with 19 other CAV strains demonstrated 94.4% to 99.4%
      homology. Slovenian isolates shared highest homology with the BD-3 isolate from
      Bangladesh. Alignment of the deduced VP1 amino acids showed that the Slovenian
      isolates shared 100% homology and had an amino acid sequence most similar to the
      BD-3 strain from Bangladesh (99.6%) and were 99.1% similar to the G6 strain from
      Japan and the L-028 strain from the United States. The Slovenian isolates were
      least similar (96.6%) to the 82-2 strain from Japan. A phylogeneric analysis on
      the basis of the alignment of the VP1 amino acids showed that CAV isolates used
      in the study formed three groups that indicated the possible existence of genetic
      groups among CAV strains. The CAV isolates were grouped together independent of
      their geographic origin and pathogenicity.

PMID- 16617986
TI  - Virulence genotyping of Salmonella spp. with multiplex PCR.
AB  - The purpose of this study was to develop a multiplex polymerase chain reaction
      (PCR) protocol useful in the virulence genotyping of Salmonella spp. with the
      idea that genotyping could augment current Salmonella characterization and typing
      methods. Seventeen genes associated with Salmonella invasion, fimbrial
      production, toxin production, iron transport, and intramacrophage survival were
      targeted by three PCR reactions. Most of these genes are required for full
      Salmonella virulence in a murine model, and many are also located on Salmonella
      pathogenicity islands (PAIs) and are associated with type III secretion systems
      (TTSSs). Once the success of procedures that used positive and negative control
      strains was verified, the genotypes of 78 Salmonella isolates incriminated in
      avian salmonellosis (primarily from sick, commercially reared chickens and
      turkeys) and 80 Salmonella isolates from apparently healthy chickens or turkeys
      were compared. Eleven of the 17 genes tested (invA, orgA, prgH, tolC, spaN
      [invJ], sipB, sitC, pagC, msgA, spiA, and iroN) were found in all of the
      isolates. Another (sopB) was present in all isolates from sick birds and all but
      one isolate from healthy birds. The remaining five genes (lpfC, cdtB, sifA, pefA,
      and spvB) were found in 10%-90% of the isolates from sick birds and 3.75%-90% of
      the healthy birds. No significant differences in the occurrence of these genes
      between the two groups of isolates were detected. These results suggest that
      these virulence genes, and presumably the PAls and TTSSs with which they are
      associated, are widely distributed among Salmonella isolates of birds, regardless
      of whether their hosts of origin have been identified as having salmonellosis.

PMID- 16617987
TI  - Onset of immunity with Mycoplasma synoviae: comparison of the live attenuated
      vaccine MS-H (Vaxsafe MS) with its wild-type parent strain (86079/7NS).
AB  - The onset of protective immunity with MS-H was determined through experimental
      challenge and compared with the parent strain 86079/7NS. MS-H vaccinates and
      86079/7NS inoculates were challenged at 1, 2, 3, 4, 5, and 6 wk after
      vaccination, then examined 2 wk after challenge for signs of respiratory disease.
      Serologic results indicated that 100% of MS-H vaccinates had antibodies to MS by
      3 wk after vaccination and 100% of 86079/7NS inoculates were positive by 2 wk
      after inoculation. From 3 wk after vaccination, MS-H vaccinates had a
      significantly lower incidence of air sac lesions and, from 4 wk after
      vaccination, a significantly lower air sac lesion severity. In 86079/7NS
      inoculated birds, a significantly lower incidence of air sac lesions was observed
      from 1 wk after inoculation, and air sac lesion severity was significantly lower
      than the unvaccinated controls at 3 wk after inoculation. It would appear that,
      under the conditions of this experiment, protective immunity elicited by MS-H
      appeared at 4 wk after vaccination, slightly later than the appearance of serum
      antibody. Although the MS-H vaccine was slower to establish protective immunity
      than 86079/7NS, there was no significant difference between the two strains by 4
      wk after vaccination or inoculation.

PMID- 16617988
TI  - Determination of the effective dose of the live Mycoplasma synoviae vaccine,
      Vaxsafe MS (strain MS-H) by protection against experimental challenge.
AB  - The minimum effective dose of the Mycoplasma synoviae-H (MS-H) vaccine was
      determined through protection against experimental challenge. Chickens were
      vaccinated by eyedrop with the following doses of a vaccine: 1.2 x 10(5), 2.4 x
      10(5) 4.8 x 10(5), 9.6 x 10(5), 1.92 X 10(6), and 3.84 X 10(6) color change units
      (CCU), then challenged 6 wk after vaccination. Rapid serum agglutination results
      indicated that 100% of birds receiving an MS-H dose of > or = 4.8 x 10(5) CCU had
      antibodies to MS and enzyme-linked immunosorbent assay results showed that 60% of
      birds receiving a dose of 4.8 x 10(5) or 9.6 x 10(5) CCU and 100% of birds
      receiving a dose of 1.92 x 10(6) or 3.84 x 10(6) had antibodies to MS. At
      postmortem after challenge, the following parameters were significantly lower in
      birds vaccinated with an MS-H dose of > or = 4.8 x 10(5) CCU: air sac (AS) lesion
      severity; incidence of AS lesions; mucosal thicknesses in the upper trachea,
      middle trachea, and lower trachea (LT); and MS colonization of the LT and AS. It
      was concluded that an MS-H dose of 4.8 x 10(5) CCU was sufficient to elicit an
      antibody response in birds, prevent MS colonization in the LT and AS, and protect
      against AS lesions caused by an experimental MS and infectious bronchitis virus
      challenge.

PMID- 16617989
TI  - Development of a polymerase chain reaction procedure for detection and
      differentiation of duck and goose circovirus.
AB  - This article reports the complete nucleotide sequences of four duck circovirus
      (DuCV) isolates from sick ducks in Taiwan and development of a polymerase chain
      reaction (PCR) for detection and differentiation of goose circovirus (GoCV) and
      DuCV. Sequence comparison showed that Taiwanese DuCV isolates had 82.5%-83.8%
      nucleotide sequence identity to the German and North American DuCV isolates. This
      is the first report on the presence of DuCV and its associated diseases outside
      Germany. A PCR test was developed using a universal primer pair based on
      conserved sequences present in the genomes of GoCV and DuCV. This PCR test could
      detect and differentiate between GoCV and DuCV by the size of PCR product each
      virus produced (256 bp for GoCV and 228 bp for DuCV). Application of this PCR
      test to samples of bursa of Fabricius from sick birds in the field showed that 9
      of 26 goose samples contained GoCV, while 13 of 34 duck samples contained DuCV.
      This PCR test could serve as a fast and sensitive method for detection and
      differentiation of DuCV and GoCV.

PMID- 16617990
TI  - Examination of the effect of a naturally occurring mutation in glycoprotein L on
      Marek's disease virus pathogenesis.
AB  - We recently reported a comparison of glycoprotein-encoding genes of different
      Marek's disease virus pathotypes (MDVs). One mutation found predominantly in very
      virulent (vv)+MDVs was a 12-bp (four-amino acid) deletion in the glycoprotein L
      (gL)-encoding gene in four of 23 MDV strains examined (three were vv+MDVs and one
      was a vvMDV). This mutation was noted in the gL of the TK (615K) strain, but not
      in the RL (615J) strain of MDV. These strains have identical mutations in the meq
      gene characteristic of vv+MDVs but can be distinguished by the mutation in the gL
      encoding gene. The TK strain was originally isolated from vaccinated chickens and
      appeared to confer or enhance horizontal transmission of the vaccine virus,
      herpesvirus of turkeys (HVT). Because the molecular basis for increased virulence
      of MDV field strains is unknown, we hypothesized that one mechanism might be by
      coreplication of MDV-1 strains with HVT and that it could be mediated by the
      mutation of gL, an essential component of the glycoprotein H/L complex. In this
      study, we compared the pathogenicity of TK (615K) and RL (615J) strains of MDV in
      the presence and absence of simultaneous HVT coinfection. MDV infections were
      monitored at the levels of viremia (for both MDV-1 and HVT), clinical signs of
      MD, tumor incidence, and mortality in 1) inoculated chickens, 2) chickens exposed
      at 1 day of age, 3) chickens exposed at 2 wk of age, and 4) chickens exposed to
      both TK/HVT- and RL/HVT-infected chickens at 6 wk of age. We found high
      incidences of clinical MD signs in all inoculated treatment groups and all
      chickens exposed to TK and RL viruses, regardless of the presence of HVT. The
      median time to death of chickens exposed to TK1HVT-infected chickens, however,
      was lower than the other treatment groups for contact-exposed chickens. Although
      this difference was not considered to be statistically significant to a
      rigorously interpreted degree because of the removal of chickens for sampling
      from the test groups, these data suggest that replication of the TK strain and
      HVT, when coadministered, might incrementally affect the virulence of MDV-1
      strains. The strict correlation of this enhancement of virulence with the
      mutation in gL, however, requires additional experiments with genetically
      identical MDV background strains.

PMID- 16617991
TI  - Detection of antibodies against serotypes 1 and 2 infectious bursal disease virus
      by commercial ELISA kits.
AB  - Two distinct serotypes of infectious bursal disease virus (IBDV) are recognized
      in chicken and turkey flocks in the United States. Serologic testing of chicken
      flocks for serotype 1 viruses is routinely performed to monitor disease status
      and vaccination. Earlier studies indicated that enzyme-linked immunosorbent assay
      (ELISA) test detects antibodies to both serotypes of the virus, while the virus
      neutralization (VN) test is serotype specific. It is useful to evaluate currently
      available commercial ELISA kits for their ability to differentiate between
      antibodies elicited by the two serotypes. Three trials were performed in which
      chickens were orally inoculated with either a high or a low dose of serotype 1
      STC or serotype 2 OH strains of IBDV. Sera collected at 0, 7, 14, and 21 days
      from these chickens and antisera procured from naturally infected broiler (n=20)
      and layer (n=30) flocks were tested with five different commercial ELISA kits and
      by VN. All ELISA kits detected different levels of antibodies elicited against
      serotype 1 of the virus and moderate and high levels of antibodies against
      serotype 2 virus. A correlation existed between the ELISA and the VN titers of
      experimentally infected chickens. All serum samples tested from the commercial
      layer flocks and 65% of the broiler flocks had antibodies against the OH strain.
      However, no correlation between the VN titers and ELISA titers was observed for
      the commercial broilers and layers sera by the majority of the kits. The results
      indicated that currently available commercial ELISA kits detect antibodies
      elicited by the two serotypes of IBDV. Hence, the prevalence of serotype 2
      antibodies in the flocks should be considered while determining antibody profiles
      of the flocks against serotype 1 viruses.

PMID- 16617992
TI  - Application of polymerase chain reaction based on ITS1 rDNA to speciate Eimeria.
AB  - A method was developed to recover Eimeria spp. oocysts directly from poultry
      litter and determine which species of Eimeria were present using polymerase chain
      reaction (PCR) based on the ITS1 rDNA sequence. The species composition of
      Eimeria oocysts was also compared before and after propagation in susceptible
      chickens to determine if the relative proportion of each species changed after
      expansion. In samples from two broiler operations, ITS1-PCR was able to detect
      Eimeria spp. oocysts recovered from litter, with Eimeria acervulina, Eimeria
      maxima, and Eimeria praecox being the predominant species present therein.
      Although Eimeria tenella was found in one sample, the other species--Eimeria
      brunetti, Eimeria necatrix, and Eimeria mitis-were not detected. The species
      composition as determined by ITS1-PCR did not appear to appreciably alter after
      expansion in susceptible chickens. The described method represents a rapid means
      for determining the major Eimeria species in a poultry operation and may be
      helpful in choosing a particular live oocyst vaccine formulation to protect
      chickens against coccidiosis.

PMID- 16617993
TI  - Effect of subtherapeutic antimicrobials on genetic diversity of Enterococcus
      faecium from chickens.
AB  - The effect of growth promotants (bacitracin, virginiamycin, and flavomycin) on
      the genetic population of Enterococcusfaecium isolated from a commercially
      integrated poultry farm was examined. A total of 551 E. faecium were isolated
      from chick boxliners (n=16), litter (n=334), feed (n=67), and carcass rinse
      (n=134) samples from four chicken houses. Two houses on the farm were control
      houses and did not use any antimicrobials while two other houses on the farm used
      flavomycin, virginiamycin, and bacitracin during six different chicken grow outs.
      BOX-PCR and pulsed-field gel electrophoresis (PFGE) results indicated that E.
      faecium strains had a high degree of genetic diversity as overall clustering was
      independent of source, house, or grow out. Similarity of > or =60% for the
      majority of BOX-PCR genogroups and > or =80% for the majority of PFGE genogroups
      was observed for a subset of carcass rinse samples (n=45) examined. Seventy-nine
      percent (19/24) of isolates in BOX-PCR genogroup 2 also clustered in PFGE
      genogroup 2, although no association between the isolates and house or grow out
      was observed. These results suggest that E. faecium from chicken are genetically
      diverse and that growth-promoting antimicrobials do not affect the genetic
      population of E. faecium.

PMID- 16617994
TI  - An outbreak of the polyomavirus infection in budgerigars and cockatiels in
      Slovakia, including a genome analysis of an avian polyomavirus isolate.
AB  - In winter 2003-04, large numbers of budgerigars (Mellopsitacus undulatus) and
      cockatiels (Nymphicus hollandicus) fell ill and died in a large parrot-breeding
      aviary in Slovakia. In budgerigars, the disease outbreak occurred at the age of 2
      3 weeks; cockatiels died within their first 7 days of life. In budgerigars,
      symptoms of the disease included delayed growth, tremor, darkish discoloration of
      skin, quill bleeding, and feathering defects. cockatiels often died without any
      symptoms and with a full crop; feathering defects occurred sporadically. Electron
      microscopy with negative staining of aqueous lysates of the affected skin and of
      bleeding quills showed isolated or clustered polyomavirus particles 45-50 nm in
      size. Long filamentous forms of the virus were also found in virion clusters of
      skin lysates from the budgerigars. In ultrathin sections through the
      pathologically altered skin tissue of budgerigars, virus particles were present
      in both nuclei and cytoplasm of epidermal cells, often in crystalline form. In
      infected cells, enlarged nuclei showed an extensive chromatin margination. On the
      DNA level, presence of a polyomavirus infection was conclusively proved by the
      polymerase chain reaction using avian polyomavirus (APV)-specific primers. A
      sequence analysis of the gene encoding viral protein (VP)1 and of the combined
      region for VP2 and VP3 proteins revealed a previously undescribed synonymous
      mutation in this isolate. This report extended the knowledge of the area of APV
      occurrence and of the spectrum of hosts in the context of genomic and morphologic
      variability of APV isolates.

PMID- 16617995
TI  - Serological evidence of chicken infectious anemia virus in the United States at
      least since 1959.
AB  - A retrospective, serological survey was performed to determine an approximate
      time frame for when chickens were first exposed to chicken anemia virus (CAV) in
      the southeastern United States. A serum collection covering most of the period
      between 1959 and 2005 was available for the present study. These sera were
      obtained from adult chicken flocks that were maintained in experimental chicken
      farms at Auburn University's Department of Poultry Science. Sera were tested for
      the presence of CAV-specific antibodies using a commercially available
      competitive enzyme-linked immunosorbent assay (ELISA) kit. Values <0.6 were
      considered positive. Fresh sera obtained from hens in 2005 showed 45.5% negative
      and 54.5% positive for CAV antibodies. The assessment of serum samples covering
      the time period of 1959 through 1979 resulted in most sera being positive for CAV
      antibodies. The percentage of positive samples between years varied from 43% to
      100%. These serological results support assumptions based on circumstantial
      evidence that CAV must have been present in the United States long before its
      first isolation in 1989.

PMID- 16617996
TI  - Expression of calbindin-D28K in sporadic nephroblastomas of the chicken.
AB  - Calbindin-D28K (Ca-D28K) is a calcium-binding protein. In the kidney, Ca-D28K is
      present in the distal nephron, but not in the proximal nephron. This site
      specific distribution in the kidney indicates that Ca-D28K is a potential marker
      for the differentiation of the distal nephron. In this study, we have examined
      the expression of Ca-D28K in 25 sporadic cases of chicken nephroblastomas. All
      cases of nephroblastomas were composed of atypical tubular structures, blastemal
      cells, and fibrous stroma in varying degrees of differentiation.
      Immunohistochemically in all nephroblastoma specimens, Ca-D28K was expressed in
      the epithelial cells of the subsets of tubular structures, but not in the
      blastema or the stroma. These results suggested that the tubuli in the
      nephroblastomas are able to differentiate into the phenotype of distal nephrons.
      Furthermore, Ca-D28K might develop as a novel diagnostic marker for
      nephroblastomas because this molecule is reported to be completely negative in
      other renal tumors, including renal cell carcinoma, chromophobe carcinomas, and
      oncocytoma.

PMID- 16617997
TI  - Experimental inoculation of wild turkeys (Meleagris gallopavo) with Mycobacterium
      bovis.
AB  - Although avian species are known to be susceptible to infection with
      Mycobacterium spp. organisms, much remains unknown about the susceptibility of
      birds to infection with M. bovis. The objective of this current study was to
      determine if wild turkeys (Meleagris gallopavo) can be infected with M. bovis
      when inoculated by the oral or intratracheal route. Six turkeys were orally
      inoculated and another six were inoculated via the trachea with a high dose of M.
      bovis, 1 x 10(5) CFU/ml. Six turkeys were sham-inoculated controls. Two turkeys
      from each treatment group were sacrificed on days 30, 60, and 90 postinoculation.
      There were no gross or microscopic lesions consistent with mycobacteriosis in the
      23 inoculated turkeys over the 90-day duration of this study. Fecal cultures were
      also consistently negative for M. bovis when sampled before inoculation and on
      days 1, 30, and 60 postinoculation. Two intratracheally inoculated turkeys were
      positive for M. bovis in visceral tissues at 30 days postinoculation. However,
      this finding was only indicative of passive persistence of mycobacteria in the
      tissues and not of infection, as there were no attendant lesions or clinical
      compromise to support infection. Thus, it can be concluded that young wild
      turkeys are resistant to infection with M. bovis and, therefore, pose minimal
      threat as reservoir or spillover hosts for this organism.

PMID- 16617998
TI  - Otitis interna (labyrinthitis) associated with Salmonella enterica arizonae in
      turkey poults.
AB  - Otitis interna was diagnosed in five 9-to-21-day-old turkey poults with clinical
      signs of paralysis, opisthotonus, torticollis, blindness, and increased
      mortality. Gross and microscopic lesions in the poults included omphalitis,
      typhlitis, hepatitis, meningoencephalitis, ophthalmitis, neuritis and
      ganglionitis of the vestibulocochlear nerve, and otitis interna. Salmonella
      enterica arizonae was isolated from the brains, eyes, intestines, yolk sacs, and
      livers of poults. Birds with otitis interna also had meningoencephalitis. It is
      most likely that the S. enterica arizonae infection spread from the brain to the
      internal ears through the vestibulocochlear nerve. This is the first
      documentation of otitis interna caused by bacteria in an avian species.

PMID- 16617999
TI  - Encephalomalacia with Enterococcus durans infection in the brain stem and
      cerebral hemisphere in chicks in Japan.
AB  - Fourteen chicks, 7-12 days old, that died or had neurological signs (depression,
      paralysis, torticollis, incoordination, and rolling) were investigated
      pathologically and microbiologically. Variably sized foci of malacia were present
      within the parenchyma of the brain stem (cerebral peduncle, optic lobe, and
      medulla oblongata) and the cerebral hemisphere. Capillary thrombosis with
      congestion and hemorrhage was frequently observed within the malacia lesions.
      Gram-positive cocci were recognized in the blood capillary of malacia lesions.
      Bacteriologically, Enterococcus durans was isolated from the brain, liver,
      kidney, lung, and spleen. Detection of gram-positive cocci within the blood
      vessels in the malacia lesions observed in these cases may more strongly suggest
      the pathogenic role of E. durans on the malacia lesions in the brain stem and
      cerebral hemisphere.

PMID- 16618000
TI  - Epidemiological investigation, cleanup, and eradication of pullorum disease in
      adult chickens and ducks in two small-farm flocks.
AB  - Pullorum disease causing acute septicemia and mortality in adult brown chickens
      was diagnosed in a small-farm chicken flock in Iowa. Also, Salmonella Pullorum
      was isolated from the intestine of one of four rats trapped on this index farm.
      Tracing movements of spent hens from the index farm resulted in identification of
      a second infected flock on a contact farm. Poultry on the contact farm were
      tested with the stained-antigen, rapid whole-blood test, and two ducks and one
      chicken gave positive reactions. Reactors were necropsied and cultures of
      appropriate tissues resulted in isolation of Salmonella Pullorum from one duck
      and the chicken. Pulsed-field gel electrophoresis banding patterns of Salmonella
      Pullorum isolates from chickens on the index and contact farms, the duck, and the
      rat demonstrated that all isolates were genetically very similar. Both flocks
      were quarantined and depopulated and a detailed flock cleanup plan was created
      for both farms. After extensive cleaning and disinfection procedures were
      completed on the index farm, environmental monitoring and bioassays of trapped
      mice were conducted. Negative cultures of environmental swabs and trapped mice
      and negative blood tests of all birds conducted 4 mo after placement of a new
      flock on the index farm demonstrated that cleaning and disinfection methods used
      in this outbreak had successfully eliminated Salmonella Pullorum organisms from
      this farm.

PMID- 16618001
TI  - Neonatal osteomyelitis associated with Staphylococcus aureus in turkey poults.
AB  - A case of Staphylococcus aureus infection causing osteomyelitis in young turkey
      poults is described. Mortality during the first week after hatching was 12.6%.
      Poults showed leg weakness, inflammation of all four toes, swelling of feet and
      hock joints, and osteomyelitis of the proximal tibiotarsus. Staphylococcus aureus
      was isolated from exudate in the hock joints and footpads. Granulocytic
      infiltration and colonies of gram-positive coccoid bacteria compatible with S.
      aureus were found on microscopic examination of the lesions. Toe trimming after
      hatching is believed to have provided a portal of entry for S. aureus, which
      resulted in infection of the toes and spread along tendons to joints and bones of
      the leg. Neonatal staphylococcal osteomyelitis should be considered when recently
      placed turkey flocks experience increased mortality, especially if they develop
      severe swelling and inflammation of toes following trimming and have enlarged
      swollen feet, tendons, or joints.

PMID- 16618002
TI  - Pathology of cutaneous fowlpox with amyloidosis in layer hens inoculated with
      fowlpox vaccine.
AB  - Cutaneous fowlpox occurring in vaccinated layer hens was investigated
      pathologically and microbiologically. Anorexia, decrease of egg production,
      increased mortality, yellow scabs on faces, and alopecia of feathered skins with
      yellow scabs were observed in affected hens. Histologically, proliferative and
      necrotic dermatitis with eosinophilic ring-shaped cytoplasmic inclusions
      (Bollinger bodies) and clumps of gram-positive cocci (Staphylococcus hyicus) were
      noted in the affected birds. Fowlpox lesions were primarily observed in the
      feathered skins. Proliferation of feather follicle epidermal cells, with
      cytoplasmic inclusions and degeneration of the feather, and bacterial clumps in
      the feather follicles were noted in the affected skins. Ultrastructurally,
      characteristic fowlpox viral particles were observed in the cytoplasmic
      inclusions of hyperplastic epidermal cells. Amyloid deposition was observed in
      the Disse space of the liver, splenic sinus, and lamina propria of the
      bronchiolar, bronchial, and tracheal areas. Amyloidosis could be one factor
      inducing the fowlpox infection in vaccinated chickens.

PMID- 16618003
TI  - Ending the darkness of suicide.

PMID- 16618004
TI  - The neuropsychological correlates of borderline personality disorder and suicidal
      behaviour.
AB  - OBJECTIVE: In subjects with borderline personality disorder (BPD), compared with
      subjects who attempted suicide, to review neuropsychological (NP) function that
      may predispose to suicidal behaviour along a continuum of high and low lethality.
      METHOD: We undertook electronic searches of MEDLINE, PsycINFO, EMBASE, Biosos
      Reviews, and Cinhal. The searches were restricted to English-language
      publications from 1985 onward. The search terms borderline personality disorder,
      suicide, suicide attempt, self-harm behaviour, neuropsychological, executive
      function (EF), neurocognitive, and neuropsychological function produced 29
      neuropsychology studies involving BPD and 7 neuropsychology studies of suicide
      attempters, regardless of psychiatric diagnosis. RESULTS: Of the BPD studies, 83%
      found NP impairment in one or more cognitive domains, irrespective of depression,
      involving specific or generalized deficits linked to the dorsolateral prefrontal
      and orbitofrontal regions. The functions most frequently reported (in 71% to 86%
      of BPD studies) are response-inhibitory processes affecting executive function
      performance that requires speeded attention and visuomotor skills. Decision
      making and visual memory impairment are also most frequently affected; 60% to 67%
      of BPD studies report attentional impairment, verbal memory impairment, and
      visuospatial organizational impairment. Least affected processes in BPD appear to
      involve spatial working memory, planning, and possibly, IQ. The similarities in
      NP deficits found in BPD and suicide-attempt studies involve decision making and
      Trails performances. BPD studies, however, reflect more frequent impairment on
      the Stroop Test and Wisconsin Card Sort Test performance than the suicide-attempt
      studies, whereas verbal fluency appears to be more frequently impaired in those
      attempting suicide. CONCLUSIONS: Impaired EF and disinhibitory processes, as
      indicated by verbal fluency, Trails, and Stroop performance, primarily associated
      with dorsolateral prefrontal cortical regions may represent a dominant executive
      pathway to suicide attempt. A primary motivational inhibitory pathway involving
      conflictual, affective, and reflexive decision-making processes associated with
      orbitofrontal brain regions, in combination with significant cognitive rigidity,
      may influence the repetitive expression of self-harm or low-lethality suicidal
      behaviour. The hypothesis of a specific trait-like cognitive vulnerability for
      suicidal behaviour involving dysregulatory, disinhibiting pathways awaits
      confirmation.

PMID- 16618005
TI  - Suicide and its prevention among older adults.
AB  - OBJECTIVE: To review the research on the epidemiology, risk and resiliency,
      assessment, treatment, and prevention of late-life suicide. METHOD: I reviewed
      mortality statistics. I searched MEDLINE and PsycINFO databases for research on
      suicide risk and resiliency and for randomized controlled trials with suicidal
      outcomes. I also reviewed mental health outreach and suicide prevention
      initiatives. RESULTS: Approximately 12/100,000 individuals aged 65 years or over
      die by suicide in Canada annually. Suicide is most prevalent among older white
      men; risk is associated with suicidal ideation or behaviour, mental illness,
      personality vulnerability, medical illness, losses and poor social supports,
      functional impairment, and low resiliency. Novel measures to assess late-life
      suicide features are under development. Few randomized treatment trials exist
      with at-risk older adults. CONCLUSIONS: Research is needed on risk and resiliency
      and clinical assessment and interventions for at-risk older adults. Collaborative
      outreach strategies might aid suicide prevention.

PMID- 16618006
TI  - Profile of a metropolitan North American immigrant suicidal adolescent
      population.
AB  - OBJECTIVE: Canadian immigrant adolescents have a lower suicide rate than their
      nonimmigrant peers. We conducted a hypothesis-generating analysis to determine
      whether this lower rate correlated with level of drug use and (or) with
      diagnostic and demographic characteristics of Canadian immigrant adolescents
      presenting to an emergency room for crisis assessment. METHOD: Known risk factors
      for suicide were compared among immigrant youth, North American youth, and a
      culturally mixed group of youth at baseline and at 6-month follow-up. RESULTS:
      The immigrant group was only differentiated by a lower rate of reported drug use.
      CONCLUSION: The lower rate of reported drug use at the time of crisis may
      contribute to the lower suicide rate among immigrants.

PMID- 16618007
TI  - Body image, binge eating, and bulimia nervosa in male bodybuilders.
AB  - OBJECTIVE: Male bodybuilders (MBB) exhibit more severe body dissatisfaction,
      bulimic eating behaviour, and negative psychological characteristics, compared
      with male athletic and nonathletic control subjects, but few studies have
      directly compared MBB and men with eating disorders. This study compared men with
      bulimia nervosa (MBN), competitive male bodybuilders (CMBB), and recreational
      male bodybuilders (RMBB) on a broad range of eating attitudes and behaviours and
      psychological characteristics to more accurately determine similarities and
      differences among these groups. METHOD: Anonymous questionnaires, designed to
      assess eating attitudes, body image, weight and shape preoccupation, prevalence
      of binge eating, weight loss practices, lifetime rates of eating disorders,
      anabolic androgenic steroid (AAS) use, and general psychological factors, were
      completed by 22 MBN, 27 CMBB, and 25 RMBB. RESULTS: High rates of weight and
      shape preoccupation, extreme body modification practices, binge eating, and
      bulimia nervosa (BN) were reported among MBB, especially among those who
      competed. CMBB reported higher rates of binge eating, BN, and AAS use compared
      with RMBB, but exhibited less eating-related and general psychopathology compared
      with MBN. Few psychological differences were found between CMBB and RMBB.
      CONCLUSIONS: MBB, especially competitors, and MBN appear to share many eating
      related features but few general psychological ones. Longitudinal research is
      needed to determine whether men with a history of disordered eating or BN
      disproportionately gravitate to competitive bodybuildin and (or) whether
      competitive bodybuilding fosters disordered eating, BN, and AAS use.

PMID- 16618008
TI  - "Hitting" voices of schizophrenia patients may lastingly reduce persistent
      auditory hallucinations and their burden: 18-month outcome of a randomized
      controlled trial.
AB  - OBJECTIVE: This study aimed to investigate the outcome of an 18-month randomized
      controlled trial (RCT) on subjective burden and psychopathology of patients
      suffering from schizophrenia. METHOD: An RCT was used to compare hallucination
      focused integrative treatment (HIT) and routine treatment (RT) in schizophrenia
      patients who persistently hear voices. We performed an intent-to-treat analysis
      on each of the 63 patients who were assessed at baseline, 9, and 18 months. On
      each of the 3 occasions, the differential effects of the treatment conditions
      were tested repeatedly. Sex, age, education, and illness (hallucination) duration
      were used as covariates. RESULTS: Patients in the experimental group retained
      improvements over time. Improvements in hallucinations, distress, and negative
      content of voices remained significant at the 5% level. CONCLUSION: HIT seems to
      be an effective treatment strategy with long-lasting effects for treatment
      refractory voice-hearing patients.

PMID- 16618009
TI  - Association between antidepressant use and prescribing of gastric acid
      suppressants.
AB  - OBJECTIVE: To determine whether an increased risk of gastrointestinal events is
      present in younger, generally healthy adults who consume antidepressants. METHOD:
      We performed a retrospective cohort study using the pharmacy records of Canadian
      Forces (CF) members who received antidepressants between June 1997 and November
      2002, excluding those taking bupropion for smoking cessation. The control cohort
      comprised members who received salbutamol. Changes in use of gastric acid
      reducing agents (GARs) and incident GAR prescribing rates were compared pre- and
      postinitiation of target medications. We performed ogistic regression analyses to
      evaluate the effects of age, sex, and concomitant medication use on GAR
      prescribing. RESULTS: A total of 8722 antidepressant exposures were identified
      among 5588 CF members. The control cohort consisted of 3059 people with 4154
      salbutamol exposures. The number of incident GAR prescriptions decreased in both
      groups postexposure; however, the rate of decrease was significantly greater
      among salbutamol users (odds ratio 1.38; 95%CI, 1.12 to 1.71). Antidepressant
      users were significantly more likely to receive a new prescription for GAR
      following both short-term and long-term exposure (adjusted odds ratio 4.93;
      95%CI, 2.66 to 9.21 and 2.83; 95%CI, 2.05 to 3.92, respectively). Antiplatelet
      agents, bisphosphonates, oral corticosteroids, and nonsteroidal antiinflammatory
      drugs were significant predictors of GAR prescription. CONCLUSION: Consistent
      with other reports, this study has identified that antidepressant use increases
      the risk for use of a gastric acid suppressant. Careful consideration should thus
      be made with regard to increased gastric event risk among antidepressant users.

PMID- 16618010
TI  - The epidemiology of psychological problems in the elderly.
AB  - OBJECTIVE: To determine the prevalence of mood, anxiety, and other disorders in
      the population of Canadians aged 55 years and over. METHOD: We undertook an
      analysis of the Canadian Community Health Survey: Mental Health and Well-Being
      (CCHS 1.2). RESULTS: There was a linear decrease for all disorders after age 55
      years. This was true for men and women; for anglophones, francophones, and
      allophones; and for both people born in Canada and people who immigrated to
      Canada after age 18 years. Consistent with previous research, the prevalences
      were higher for women than men. Immigrants reported fewer problems than
      nonimmigrants, with the differences decreasing with age. Francophones of both
      sexes reported more mood disorder than anglophones, but francophone men had less
      anxiety disorder than anglophone men. CONCLUSIONS: Unlike other studies that have
      found an upturn in the prevalence of depression and anxiety in the elderly, our
      results indicate a steady decrease in these disorders. Our findings are discussed
      in terms of explanations for age-related differences in psychiatric disorders.

PMID- 16618011
TI  - Metformin for prevention of weight gain and insulin resistance with olanzapine: a
      double-blind placebo-controlled trial.
AB  - OBJECTIVE: To assess whether metformin prevents body weight gain (BWG) and
      metabolic dysfunction in patients with schizophrenia who are treated with
      olanzapine. METHOD: Forty patients taking olanzapine (10 mg daily) were randomly
      allocated to a metformin (n = 20; 850 to 1700 mg daily) or placebo (n = 20) group
      in a 14-week double-blind study. Waist circumference (WC), BWG, body mass index
      (BMI) fasting glucose, insulin, and lipids were evaluated at baseline and at
      Weeks 7 and 14 of treatment. RESULTS: At Week 14, BWG (kg) was similar in the
      metformin group (5.5 kg) and the placebo group (6.3 kg), P = 0.4. There were no
      differences between the changes in BMI, WC, glucose, insulin, insulin resistance
      index (HOMA-IR), and plasma lipid levels observed in the treatment group and the
      placebo group; however, glucose levels decreased significantly after metformin
      administration (P = 0.02). The HOMA-IR decreased significantly in both groups,
      but 3 subjects from the placebo group developed fasting glucose levels greater
      than 5 mmol/L. After taking metformin, triglyceride levels increased, but the
      cholesterol profile improved significantly. CONCLUSIONS: Metformin did not
      prevent olanzapine-induced BWG. While some lipid parameters worsened during
      placebo, the HOMA-IR improved in both the placebo and the metformin groups.
      Carbohydrate metabolism impairment was not systematically observed during short
      term olanzapine administration.

PMID- 16618012
TI  - Re: psychiatry in the Nazi era.

PMID- 16618013
TI  - Bioequivalence of a novel high-dose oral formulation of alpha
      dihydroergocryptine.
AB  - The plasma pharmacokinetics of alpha-dihydroergocryptine (DHEC, CAS 14271-05-7)
      were investigated in 24 patients with Parkinson disease after the administration
      of repeated oral doses of 40 mg DHEC twice daily by means of a novel 40 mg DHEC
      tablet (Almirid 40 mg test T) and an established 20 mg DHEC tablet (Almirid 20 mg
      - reference R). The trial was conducted according to a randomised, controlled,
      open, within-subject cross-over design; steady-state was established by means of
      a stepwise up-titration from 5 to 40 mg b.i.d. from day D01 to D19;
      investigational treatments (40 mg DHEC b.i.d. by means of formulation R and T)
      were administered on day D20 and D21 according to a randomised, period-balanced
      within-subject cross-over; treatment with DHEC was down-titrated in stepwise
      fashion from day D22 to D34. Morning doses of 2 x 20 mg DHEC (reference) yielded
      a fast and relatively short lasting peak with a geometric mean Cmax of 2157 pg/mL
      (CV: 0.978) after a median tmax of 1.00 h. Cmin throughout the first 12 h was on
      average 189 pg/mL (CV: 0.908). There was a quite distinct diurnal effect: evening
      doses of 2 x 20 mg DHEC (treatment R), yielded a relatively lower exposure with
      geometric mean Cmax, Cav- and Cmin-values of 800 pg/mL (CV: 0.870), 389 pg/mL
      (0.813) and 177 pg/mL (CV: 0.942). In contrast, there was relatively little
      within-subject distinction between the two formulations: for the day profile
      after the morning dose, the estimated ratios of the true means (Pr:R) for Cmax
      Cmin and Cav were 1.18 (90% CI: 0.96 to 1.43 - CVm: 0.394), 0.96 (90% CI: 0.86 to
      1.09 - CVm: 0.230) and 1.06 (90% CI: 0.93 to 1.21 - CVm: 0.254); for the night
      profile after the evening dose, the estimated ratio of the true means (muT:muR)
      for Cmax, Cmin and Cav were 1.11 (90% CI: 0.91 to 1.35 - CVm: 0.395), 1.07 (90%
      CI: 0.95 to 1.20 - CVm: 0.232) and 1.07 (90% CI: 0.95 to 1.20 - CVm: 0.220). In
      view of important medical-ethical constraints not to expose an unreasonably high
      number of subjects, these findings could be accepted as a sufficient
      demonstration of bioequivalence.

PMID- 16618014
TI  - Investigation of the effect on photosensitivity following multiple oral dosing of
      two different hypericum extracts in healthy men.
AB  - The naphthodiantrones hypericin and pseudohypericin, ingredients of hypericum
      extracts, are known as potent photosensitizers that may cause phototoxic effects
      in grazing animals after excessive ingestion of hypericum species and in some
      cases in higher concentrations of hypericum extracts oder pure hypericin in
      humans as well. Therefore, the objective of the present studies was to
      investigate the effect of two different hypericum extracts (STW 3, STW 3-VI) on
      photosensitivity with respect to minimal erythema dose (MED) after 14 days
      treatment. Both open, multiple-dose, one-phase studies were conducted in 20
      healthy men, receiving one tablet per day. MED values were determined prior to
      hypericum extract administration (baseline) and after 14 days treatment using an
      erythem tester emitting a light very similar to sun light (main emission
      spectrum: 285-350 nm). Skin reactions with respect to MED were evaluated 12 h, 24
      h (primary endpoint), 48 h and 7 days after irradiation. All volunteers reached
      steady-state of hypericin/pseudohypericin plasma concentrations before study day
      14, when the irradiation under treatment conditions took place. In all subjects
      MED was measurable under baseline and under hypericum treatment conditions. With
      respect to the primary endpoint, in both studies, mean MED (24 h) were not
      significantly different between baseline and after 14 days hypericum treatment.
      However, individually photosensitivity of the skin could increase under treatment
      conditions, just as well photosensitivity could decrease or remain unchanged.
      There were no clinically relevant changes in the laboratory parameters, the vital
      signs, physical findings and other observations related to safety during the
      examinations. In one study (STW 3), two adverse events were reported, both
      described as hypersensitivity to light in mild Intensity. The two studies showed
      that treatment with the two hypericum extracts under steady state and under
      prescribed conditions were safe medications without significant increases of
      photosensitivity.

PMID- 16618015
TI  - Efficacy and safety of a combination of sabal and urtica extract in lower urinary
      tract symptoms. A randomized, double-blind study versus tamsulosin.
AB  - The aim of this prospective, randomized, double-blind, double-dummy, multicenter
      clinical trial was to investigate the efficacy and safety of PRO 160/120
      (Prostagutt forte), a fixed combination preparation of 160 mg Sabal fruit extract
      WS 1473 and 120 mg Urtica root extract WS 1031 per capsule, in comparison to the
      alpha1-adrenoceptor antagonist tamsulosin (CAS 106463-17-6) in lower urinary
      tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH). 140 elderly
      out-patients suffering from LUTS caused by BPH, with an initial score > or = 13
      points in the International Prostate Symptom Score (I-PSS), received 2 x 1
      capsule/d PRO 160/120 or 1 x 0.4 mg/d tamsulosin and were treated for 60 weeks
      with interim visits at weeks 8, 16, 24, 36, and 48. The primary outcome measure
      for efficacy was the change in I-PSS total score, the percentage of patients with
      an I-PSS score < or = 7 points at endpoint ('responders') was analyzed as well.
      During 60 weeks of randomized treatment the I-PSS total score was reduced by a
      median of 9 points in both groups. In total, 32.4 % of the patients in the PRO
      160/120 group and 27.9% in the tamsulosin group were responders (test for non
      inferiority of PRO 160/120: p = 0.034; non-inferiority margin 10%). Both drugs
      were well tolerated, with one adverse event in 1514 treatment days for PRO
      160/120 and one event in 1164 days for tamsulosin. The study supports non
      inferiority of PRO 160/120 in comparison to tamsulosin in the treatment of LUTS
      caused by BPH.

PMID- 16618016
TI  - Open, non-controlled clinical studies to assess the efficacy and safety of a
      medical device in form of gel topically and intravaginally used in postmenopausal
      women with genital atrophy.
AB  - Menopause is often associated with vaginal atrophy and related symptoms, such as
      vaginal dryness, burning, itching, and dyspareunia, decrease in libido and in
      general a decrease in the quality of life. The common treatment up to the 1990's
      has been the oral hormone replacement therapy (HRT), but this treatment has been
      consequently re-considered due to its adverse effects. Topical estrogenic
      products have been subsequently developed to minimize the systemic adverse
      effects of the oral HRT, but they are still considered at risk in case of
      prolonged use. As an alternative, two clinical trials were performed to
      investigate the effects of a medical device in the form of a gel, containing
      hyaluronic acid, liposomes, phytoestrogens from Humulus lupulus extract, and
      Vitamin E, with the aim of testing its safety and efficacy in post-menopausal
      women with urogenital atrophy. The first pilot study confirmed in 10 women the
      good safety profile, both locally and systemically, of the device applied on the
      external genitals at the dose of 1-2 g/day for 30 days. The second study was
      carried out, according to a multicenter, open, non-controlled design, in 100 post
      menopausal women assigned to the vaginal application of 2.5 g of gel/day for 1
      week followed by two applications/week for 11 weeks. The primary end-point was
      the evaluation of vaginal dryness assessed by a Visual Analogue Scale both by the
      investigator and the subject. Secondary endpoints were the evaluation of all
      other symptoms and signs associated with atrophic vaginitis (itching, burning,
      dyspareunia, vaginal inflammation/oedema and rash assessed by a 4-point scale and
      presence of vaginal abrasions and disepithelialisation), and the recording of
      adverse events during the study. At the end of the treatment, an overall judgment
      on the efficacy and safety of the device was made by the investigator and a
      judgment on the acceptability of the treatment was made by the subjects. The
      results showed a marked effect of the tested product on the vaginal dryness and
      on all other symptoms and signs with statistically significant reductions since
      the first week of treatment. No treatment-related adverse events were complained
      by the subjects and the treatment course showed a high level of acceptability by
      the subjects. This device could be considered an effective and safe alternative
      treatment of genital atrophy in post-menopausal women, especially when HRT is not
      recommended.

PMID- 16618017
TI  - Synthesis and evaluation of antimicrobial and anticonvulsant activities of some
      new 3-[2- (5-aryl-1,3,4-oxadiazol-2-yl/4-carbethoxymethylthiazol-2-yl) imino-4
      thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-ones and
      investigation of their structure-activity relationships.
AB  - In the present study, 20 new compounds having 3-[2-(5-aryl-1,3,4-oxadiazol-2-yl)
      imino-4-thiazolidinon-5-ylidene]-5-substituted/nonsubstituted 1H-indole-2-one (I
      XII) and 3-[2-(4-carbethoxymethylthiazol-2-yl)imino-4-thiazoldinon-5-ylidenel-5
      substituted/nonsubstituted IH-indole-2-one (XIII-XX) systems were synthesized.
      The structures were confirmed by spectral methods (UV, IR, 1H-NMR, 13C-NMR, 13C
      DEPT (135), electron impact mass spectrometry) and elemental analysis. All
      compounds were tested for in vitro antimicrobial activity against Staphylococcus
      aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC
      8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539,
      Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida
      albicans ATCC 10231, Microsporum gypseum (NCPF-580), Microsporum canis,
      Trichophyton mentagrophytes and Trichophyton rubrum and some of them were found
      to be active. Especially, compound I was more active than cefuroxime sodium (CAS
      56238-63-2) which was used as a standard, and the activity of compound XII was
      close to that of cefuroxime sodium against Staphylococcus epidermidis ATCC 12228.
      Primary screening for antituberculous activity was conducted at 6.25 microg/ml
      against Mycobacterium tuberculosis H37Rv in BACTEC 12B medium using the BACTEC
      460 radiometric system. The anticonvulsant activities of selected prototoype
      compounds (I, IV-VI, VIII, XI, XIII, XVI-XVIII) administered at doses of 50-200
      mg/kg (i.p.) were evaluated using the pentetrazol test (PTZ) in mice.

PMID- 16618018
TI  - [Efficacy and safety profile of a herbal drug containing nasturtium herb and
      horseradish root in acute sinusitis, acute bronchitis and acute urinary tract
      infection in comparison with other treatments in the daily practice/results of a
      prospective cohort study].
AB  - PATIENTS AND METHODS: In a prospective cohort study from 251 centers in Germany
      patients with age of 4 years or above who were treated due to acute sinusitis,
      bronchitis or urinary tract infections (UTI) in the period from 1st March 2004 -
      30th July 2005, were elected. They were included in the study analysis, if they
      had no exclusion criteria (severe diseases, need for antibiotic therapy,
      participation in another trial) and came to the final investigation. The patients
      were treated either with the nasturtium herb and horseradish root containing
      herbal drug Angocin Anti-Infekt N (test group, n = 1223) or with standard
      antibiotic therapy (control group, n = 426). Treatment, dosage and treatment
      duration were determined by the physician in accordance with the patient. 536
      subjects (408 test, 128 control patients) suffered from acute sinusitis, 634
      subjects (469 test, 165 control patients) from acute bronchitis and 479 subjects
      (346 test, 133 control patients) from UTI. At study start and end the severity of
      the symptoms were judged by the investigator and quantified with 4 scores (0 = no
      symptom, 3 severe symptom). During the treatment information on use of
      medication, concomitant procedures and adverse events (AEs) in a patient diary.
      At the end of the study (disease free or after 7-14 days) the patient returned to
      the investigator, who recorded the vital parameters, finally judged the treatment
      efficacy and potential persisting symptoms on the basis of score values. Primary
      efficacy criterion was the change of the complaints quantified by the change of
      the relative symptom score averaged over all symptoms and related to the baseline
      value. RESULTS: In patients with acute sinusitis the mean relative reduction of
      the averaged symptom score was 81.3% for the test group and 84.6% for the control
      group, in patients with acute bronchitis the mean reduction was 78.3% for the
      test group and 80.3% for the control group, in patients with UTI 81.2% for the
      test group and 87.9% for the control group. The 95% confidence interval for the
      difference of the expected reductions between test and control group was -8.5% to
      1.8% for acute sinusitis, 7.6% to 3.6% for acute bronchitis and -13.1% to -0.1%
      for UTI. Non-inferiority of the test treatment, i.e. if the lower limit of the
      95% confidence interval is greater than 10%, could be stated for acute sinusitis
      and bronchitis. In UTI the non-inferiority level was exceeded only by 3%.
      Complementary procedures were less in the test group than in the control group.
      For 1.5 % of test patients and 6.8% of control patients AEs were observed
      CONCLUSION: Therapy with the herbal drug in the indications acute sinusitis,
      acute bronchitis und acute urinary tract infection is - with regard to its
      efficacy comparable to the treatment with standard antibiotics. The application
      of supportive procedures and the administration of concurrent medication were
      less expressed in the group treated with the herbal drug. In the above mentioned
      indications the group treated with the herbal drug displayed a clear advantageous
      safety profile compared to the group treated with standard antibiotics.

PMID- 16618019
TI  - Disposition of exogenous urea and effects of diet in rats.
AB  - Although breath test using 13C-labeled urea (CAS 57-13-6, UBT) is becoming
      popular for the diagnosis of Helicobacter pylori (H. pylori) infection,
      disposition of exogenously given urea is not fully understood. The purpose of the
      present study is to elucidate the disposition of exogenous urea and to consider
      its relation with the UBT safety and biobehavior of endogenous urea. With 14C
      labeled urea ([14C]urea), the absorption, distribution, metabolism and excretion
      including that into breathed air after its administration in trace to large doses
      in rats were investigated. [14C]Urea was given to fasted and non-fasted rats
      through intravenous and oral routes. It was found that the disposition of
      exogenous [14C]urea behaves in a similar way as endogenous urea, and a
      sufficiently large capacity for disposing urea in rats was suggested from the
      linear pharmacokinetics within the wide dose range of [14C]urea (2-1000 mg/kg).
      The safety of urea in UBT was also revealed by consideration of its dose and
      human urea body pool. It was also suggested that diet stimulates both systemic
      (as observed after the intravenous dose) and pre-systemic (as with the oral
      route) decompositions of urea into carbon dioxide and ammonia, but does not
      affect the renal elimination and distribution pattern in rat tissues. The
      findings in this study provide us with the quantitative information concerning
      not only the safety and disposition of urea as a diagnostic agent, but also the
      biobehavior of endogenous urea in ureotelism.

PMID- 16618020
TI  - [Biomedical research. Hypothesis-driven or data-driven?].

PMID- 16618021
TI  - [Balloon aortic valvuloplasty in the adult. Immediate results and in-hospital
      complications in the latest series of 141 consecutive patients at the University
      Hospital of Rouen (2002-2005)].
AB  - With the aging population, elderly patients with degenerative, severely
      calcified, and symptomatic aortic stenosis are becoming a frequent problem in
      medical decision making, particularly because many are declined for surgical
      valve replacement. For these patients, balloon aortic dilatation could be a
      palliative treatment. PATIENTS AND METHODS: we analyzed retrospectively our
      techniques and complications during hospitalization for percutaneous aortic
      balloon dilatation in 141 consecutive patients (45% women, mean age 83 +/- 10 y)
      from January 2002 to April 2005. The Parsonnet's score was 41 +/- 8 and the
      Euroscore was 10 +/- 2. We excluded the patients enrolled for percutaneous aortic
      valve implantation. This technique was performed under local anesthesia, from
      retrograde or antegrade approach. Rapid pacing stimulation (220/bpm) with a
      pacing-lead placed in the right ventricle was performed during balloon inflation.
      RESULTS: the aortic valve area was increased from 0.59 +/- 0.19 to 1.02 +/- 0.34
      cm2 (p < 0.001) and the transvalvular mean gradient decreased from 49.3 +/- 21.2
      to 22.2 +/- 11.8 mmHg (p < 0.001). Six patients (4%) died (3 during aortic valve
      dilatation) and 9 patients (6%) had non fatal complications: 2 transitory
      strokes, 8 non surgical vascular complications and 5 episodes of atrio
      ventricular complete block (these complication were non exclusive). The patients
      were discharged at 5, 6 +/- 3 days. CONCLUSION: In the hands of skilled
      operators, aortic percutaneous balloon dilatation has become a simple technique,
      associated with a low risk of complications despite a very ill patient
      population. This technique remains a good option for a number of patients before
      the onset of percutaneous aortic valve implantation.

PMID- 16618022
TI  - [Type B natriuretic peptide (BNP) versus n-terminal type B natriuretic propeptide
      in the diagnosis of cardiac failure in the elderly over 75 population].
AB  - Type B natriuretic peptide (BNP) versus n-terminal type B natriuretic propeptide
      in the diagnosis of cardiac failure in the elderly over 75 population The value
      of BNP is well established in the diagnosis of cardiac failure in cases of
      dyspnoea in the emergency room in young and, more and more, in elderly subjects.
      However, there are few studies comparing the diagnostic value of BNP and of the n
      terminal pro-BNP in patients over 75 years of age. The aim of this study was to
      compare the diagnostic value of BNP and NT-pro BNP in dyspnoea of the elderly
      patient. One hundred and three consecutive patients over 75 years of age admitted
      to the emergency unit for dyspnoea were included. A blood sample for measuring
      the BNP (Biosite) and the NT-proBNP (Roche Diagnostic) was taken in the admission
      unit in addition to the standard blood workup. The final reference diagnosis was
      established by two independent cardiologists. Of the 103 patients, 61 were women
      and the average age was 84.9 +/- 6.2 years. The final diagnosis was cardiac
      failure in 49 patients (48%), pulmonary embolism in 6 patients, an acute
      exacerbation of chronic obstructive airways disease in 36 patients and an acute
      bronchitis in 30 patients. In 9 cases, the dyspnoea was considered to result from
      mixed cardiac and pulmonary disease. Renal function was assessed by calculating
      the creatinine clearance by Cockcroft and Gault's formula. The average value of
      the creatinine clearance was 41.7 +/- 16.4 ml/min indicating that mild renal
      failure was relatively common. The diagnostic value, assessed by the area under
      the ROC curve, was similar for the BNP (0.79; CI: 0.70-0.88) and NT-proBNP (0.80;
      CI: 0.71-0.89). A BNP value of 300 pg/ml had the same sensitivity and specificity
      as an NT-proBNP of less than 1 500 pg/ml. A BNP of less than 200 pg/ml and an NT
      proBNP of less than 1 000 pg/ml had excellent negative predictive values for
      excluding the diagnosis of cardiac failure. The authors conclude that the BNP and
      NT-proBNP are useful for the diagnosis of cardiac failure in acute dyspnoea of
      the elderly and seem to have a comparable diagnostic value.

PMID- 16618023
TI  - [Prognostic value of BNP for hospital mortality in elderly subjects hospitalised
      for acute diastolic cardiac failure].
AB  - The aim of this study was to evaluate the prognostic value of BNP in elderly
      patients hospitalised for acute diastolic cardiac failure. 108 consecutive
      subjects were included, aged at least 70 years old, hospitalised for isolated
      acute diastolic cardiac failure. All of them had a left ventricular ejection
      fraction > or = 50% and evidence of diastolic dysfunction on echocardiography
      performed shortly after admission. The plasma BNP concentration measured in the
      emergency department on admission was >100 pg/ml in all of the patients except
      five. It was positively correlated with age (R = 0.29, p = 0.002), with the
      plasma creatinine level (R = 0.37, p < 0.0001) and the plasma urea level (R =
      0.41, p < 0.0001). On univariate analysis, compared to the patients who survived,
      the 20 patients who died before discharge were significantly older (88.6 versus
      84.4 years, p = 0.01), and were more often residents of a care home (60 versus
      31%. p = 0.02), had a lower systolic blood pressure on admission (127 +/- 33
      versus 154 +/- 30 mm Hg), a higher plasma urea level (16.8 +/- 12 versus 8.9 +/-
      5 mmol/l, p = 0.002) and a higher BNP (median = 1290 pg/ml, interquartile range:
      721, 3026 pg/ml versus 430 pg/ml, interquartile range: 243, 886 pg/ml). On
      multivariate analysis, the only factors that remained significantly associated
      with mortality were the BNP levels (p = 0.005) and the systolic blood pressure (p
      = 0.01). The negative predictive value of a BNP level < 631 pg/ml (median) for
      death was 94% (95% confidence interval: 91 to 97%). We conclude that BNP does
      have an independent prognostic value for in-hospital death in elderly subjects
      with acute diastolic cardiac failure.

PMID- 16618024
TI  - [Hyponatraemia, antagonists of the antidiuretic hormone and cardiac failure].
AB  - Hyponatraemia is a common clinical finding in cardiac failure, complicating the
      management of these patients. Vasopressin plays a fundamental role in the
      physiopathology of the hyponatraemia of cardiac failure and binds to two distinct
      specific receptors, receptor V1a and V2. The V2 receptors, situated in the renal
      collecting duct, control the resorbtion of free water. The V1a receptors, present
      everywhere, are responsible for the vasoconstrictive effect of vasopressin.
      Specific antagonists of vasopressin receptors are being evaluated in pathologies
      associated with hyponatraemia. The preliminary results in patients with cardiac
      failure are encouraging and mortality studies are underway.

PMID- 16618025
TI  - [Clinical evolution of patients following investigation of atrial vulnerability
      after a first cerebral ischaemic accident].
AB  - Atrial vulnerability reflects the ability of the atrium to fibrillate. ISAV
      (Ischemic stroke and atrial vulnerability) is a French epidemiological registry
      whose main goal is to assess the evolution modalities of patients in whom an
      electrophysiological study of the atrium has been performed. A group of 269
      patients with a history of non elucidated ischemic stroke and an
      electrophysiological study of the atrium performed in a mean delay of 3 months
      after the stroke has been included. Their mean age at the time of the stroke was
      55 +/- 15.8 years. The electrophysiological study has measured the effective
      refractory period of the atrium, the locoregional right intra-atrial conduction
      time, the index of latent atrial vulnerability and assessed the inductibility.
      The mean delay between the date of the stroke and the date of the last news was
      4.4 +/- 2.8 years. We observed 12 deaths and 11 patients presented during the
      follow up a spontaneous atrial arrhythmia and 17 a recurrence of stroke. If we
      consider the occurrence of the 28 combined events (atrial arrhythmia and/or
      stroke), it is not correlated with the presence of an atrial septal defect nor
      with the existence of an atrial vulnerability. On the contrary this occurrence is
      correlated with tobacco consumption and/or arterial hypertension; 82% of patients
      have these risk factors versus 54% of patients without events (p = 0.004). This
      association is not significant in patients younger than 55 years.

PMID- 16618026
TI  - From molecular to modular cardiology. How to interpret the millions of data that
      came out from large scale analysis of gene expression?
AB  - Cell biology is in transition from reductionism, to a more integrated science
      which is now preoccupied by molecular interactions acting in modules. Large-scale
      quantitative analysis of gene expression, including cDNA microarrays and
      proteomic analysis, is now applied to heart failure and atherosclerosis. The
      technology is still at the beginning and is limited by variations in the array
      platforms and gene products as well as sensitivity or specificity of the selected
      probes. These limitations are progressively going to be reduced, but still they
      do exist. Biological systems are scale free networks made from genes, proteins or
      traits that interact one another and form networks and functional modules.
      Networks emerge through the addition of new nodes which are preferentially
      attached to more connected nodes to form hubs, according to the "rich-gets
      richer" mechanism, and there are large networks which include central genes
      (nexus). Both hubs and nexus are attractive candidate for targeting new therapy.
      An important study from King JY et al. (Physiol Genomics 2005; 23: 103-18)
      exemplifies this concept by showing the first realistic pathways to understand
      atherosclerosis. The 4 steps of the design are based on histological grading and
      microarrays analysis and include an association network constructed from PubMed
      and the construction of sub-networks in which genes whose expression was
      differentially regulated were indicated. Connectivity analysis networks revealed
      new important modular pathways. In heart failure, no attempts have been made to
      organize the data into functional modulus. Since the causes of heart failure are
      well documented, the problem is to identify functional modules responsible for
      myocardial dysfunction. Several potential functional modules can be identified so
      far. Indeed, cardiac remodeling results from two types of changes in gene
      expression, namelly the reexpression of the foetal programme which has a
      mechanical origin and several well documented interfering determinants that
      modified the basic remodelling, including senescence, obesity, diabetes,
      ischemia, and the neurohormonal reaction.

PMID- 16618027
TI  - Role of echocardiography in studies of murine models of cardiac diseases.
AB  - Mice are increasingly used in cardiovascular research. Echocardiography is
      uniquely suited to monitor their cardiac phenotype, as it is noninvasive and can
      be serially obtained. The present review summarizes the parameters obtained by
      echocardiography and some of its applications.

PMID- 16618028
TI  - The endogenous cardiac cannabinoid system: a new protective mechanism against
      myocardial ischemia.
AB  - The pharmacological (and recreational) effects of cannabis have been known for
      centuries. However, it is only recently that one has identified two subtypes of G
      protein-coupled receptors, namely CB1 and CB2-receptors, which mediate the
      numerous effects of delta9-tetrahydrocannabinol and other cannabinoids.
      Logically, the existence of cannabinoid-receptors implies that endogenous ligands
      for these receptors (endocannabinoids) exist and exert a physiological role.
      Hence, arachidonoylethanolamide (anandamide) and sn-2 arachidonoylglycerol, the
      first two endocannabinoids identified, are formed from plasma membrane
      phospholipids and act as CB1 and/or CB2 agonists. The presence of both CB1 and
      CB2-receptors in the rat heart is noteworthy. This endogenous cardiac cannabinoid
      system is involved in several phenomena associated with cardioprotective effects.
      The reduction in infarct size following myocardial ischemia, observed in rats
      exposed to either LPS or heat stress 24 hours before, is abolished in the
      presence of a CB2-receptor antagonist. Endocannabinoids and synthetic
      cannabinoids, the latter through either CB1 or CB2-receptors, exert direct
      cardioprotective effects in rat isolated hearts. The ability of cannabinoids to
      reduce infarct size has been confirmed in vivo in anesthetized mice and rats.
      This latter effect appears to be mediated through CB2-receptors. Thus, the
      endogenous cardiac cannabinoid system, through activation of CB2-receptors,
      appears to be an important mechanism of protection against myocardial ischemia.

PMID- 16618029
TI  - [Large coronary aneurysm diagnosed during an acute coronary syndrome. A case
      report and review of the literature].
AB  - Coronary aneurysm is an uncommon variant of coronary atherosclerosis. It usually
      involves the right coronary artery and is often associated with significant
      coronary stenosis. It may be revealed by an acute coronary syndrome (ACS). We
      report the case of a 49 year-old woman in whom a large coronary aneurysm of the
      left anterior descending artery was revealed by an ACS. Coronary angiography
      remains the gold standard diagnosis procedure, but spiral computed tomography may
      be of interest to specify the location and nature of the aneurysm, and thus guide
      surgical or percutaneous treatment.

PMID- 16618030
TI  - [Cardiogenic shock due to acute myocarditis complicating leptospirosis].
AB  - A 48 year old man was admitted to the intensive care unit with septicaemic shock
      associated with febrile jaundice and anuric renal failure. Within hours, he
      developed cardiogenic shock with multi-organ failure due to an acute myocarditis
      refractory to catecholamines and requiring intra-aortic balloon pumping. The
      diagnosis was an ictero-haemorrhagic leptospirosis, the outcome of which was
      finally favourable. Myocarditis is an underestimated complication of
      leptospirosis because it is often symptomless. The main signs are arrhythmias,
      conduction defects and ST-T wave abnormalities which have little clinical
      expression. The disease may progress and is sometimes fatal. Leptospirosis
      myocarditis should therefore be carefully considered because of its potential
      severity and its reversibility with appropriate antibiotic therapy and also the
      necessity of initial management in a specific infrastructure.

PMID- 16618031
TI  - [Spontaneous coronary artery dissection on the 10th post-partum day: a case
      report].
AB  - Spontaneous coronary artery dissection is a rare cause of myocardial infarction.
      It most commonly occurs in young women in the peri-partum period. The aetiology
      remains obscure. The authors describe the case of a 38 year old woman who
      suffered an inferior wall myocardial infarction on the 10th post-partum day.
      After failure of thrombolysis, coronary angiography showed dissection of the
      right coronary artery. An attempted angioplasty was unsuccessful and the patient
      was treated medically with a favourable clinical outcome. Spontaneous coronary
      artery dissection should be considered in all young patients without coronary
      risk factors presenting with acute myocardial ischaemia, especially young women
      in the peri-partum period. Emergency coronary angiography should be undertaken to
      establish the diagnosis and orientate appropriate treatment which may be medical,
      interventional or surgical.

PMID- 16618032
TI  - [Ictero-haemorrhagic leptospirosis with a cardiac presentation in a patient
      returning from an endemic zone].
AB  - On returning from a tropical area, the occurrence of rapidly evolving cardiogenic
      shock in an infectious context should quickly suggest the diagnosis, for which
      specific treatment can affect the outcome. The dramatic case of a young female
      presenting with ictero-haemorrhagic leptospirosis diagnosed post-mortem,
      demonstrated this pathology with the unusual association of complete atrio
      ventricular block and myocarditis in a haemorrhagic context.

PMID- 16618033
TI  - [Endovascular technique in aortic aneurysm. Results of two randomized trials].

PMID- 16618034
TI  - [Life-long mental exercise can prevent Alzheimer disease].

PMID- 16618035
TI  - [Epigenetics--cellular memories--affect disease development].

PMID- 16618037
TI  - [Contra: Natriuretic peptides as diagnostic tool. Still obstacles for routine use
      in heart failure].

PMID- 16618036
TI  - [Pro: Natriuretic peptides as diagnostic tool. The analysis should be a routine
      in heart failure diagnosis].

PMID- 16618038
TI  - [Neurocysticercosis as the cause of epileptic seizure. Rare occurrence of pork
      tapeworm infection in Scandinavia].

PMID- 16618039
TI  - [Shortly about cohort studies].

PMID- 16618041
TI  - [A joint explanatory model for diseases related to indoor environment doesn't
      exist].

PMID- 16618040
TI  - [Co-sleeping with infants--modify the advice a little bit!].

PMID- 16618043
TI  - Effects of trigger point acupuncture on chronic low back pain in elderly patients
      -a sham-controlled randomised trial.
AB  - INTRODUCTION: There is some evidence for the efficacy of acupuncture, but it
      remains unclear whether trigger point acupuncture is effective. Our objective was
      to evaluate the effects of trigger point acupuncture on pain and quality of life
      in chronic low back pain patients compared with sham acupuncture. METHODS: Twenty
      six consecutive out-patients (17 women, 9 men; age range: 65-91 years) from the
      Department of Orthopaedic Surgery, Meiji University of Oriental Medicine, with
      non-radiating low back pain for at least six months and normal neurological
      examination, were randomised to two groups. Each group received one phase of
      trigger point acupuncture and one of sham acupuncture with a three week washout
      period between them, over 12 weeks. Group A (n = 13) received trigger point
      acupuncture in the first phase and sham acupuncture in the second. Group B (n =
      13) received the same interventions in the reverse order. Outcome measures were
      pain intensity (visual analogue scale, VAS) and Roland Morris Questionnaire.
      RESULTS: Nineteen patients were included in the analysis. At the end of the first
      treatment phase, group A receiving trigger point acupuncture scored significantly
      lower VAS (P < 0.001) and Roland Morris Questionnaire scores (P < 0.01) than the
      sham control group. There were significant within-group reductions in pain in
      both groups during the trigger point acupuncture phase but not in the sham
      treatment phase. However, the beneficial effects were not sustained. CONCLUSION:
      These results suggest that trigger point acupuncture may have greater short term
      effects on low back pain in elderly patients than sham acupuncture.

PMID- 16618044
TI  - Are minimal, superficial or sham acupuncture procedures acceptable as inert
      placebo controls?
AB  - Most controlled trials of acupuncture have used minimal, superficial, sham, or
      'placebo' acupuncture. It has recently been demonstrated that light touch of the
      skin stimulates mechanoreceptors coupled to slow conducting unmyelinated (C)
      afferents resulting in activity in the insular region, but not in the
      somatosensory cortex. Activity in these C tactile afferents has been suggested to
      induce a 'limbic touch' response resulting in emotional and hormonal reactions.
      It is likely that, in many acupuncture studies, control procedures that are meant
      to be inert are in fact activating these C tactile afferents and consequently
      result in the alleviation of the affective component of pain. This could explain
      why control interventions are equally effective as acupuncture in alleviating
      pain conditions that are predominantly associated with affective components such
      as migraine or low back pain, but not those with a more pronounced sensory
      component, such as osteoarthritis of the knee or lateral epicondylalgia.

PMID- 16618045
TI  - The use of acupuncture in the treatment of temporomandibular dysfunction--an
      audit.
AB  - OBJECTIVE: Temporomandibular dysfunction often represents a major therapeutic
      problem in a dental practice. Evidence from clinical studies suggests that
      acupuncture may be useful in the treatment of temporomandibular dysfunction.
      However, most studies have been performed in university settings. The aims of
      this study were to determine if the results of acupuncture treatment of
      temporomandibular dysfunction in general dental practice are comparable to the
      results obtained in previous studies in university clinics, and whether the
      treatment approach differs from that used in previous studies. METHODS: The case
      reports submitted by 15 dentists applying for the diploma of the British Dental
      Acupuncture Society were combined into one audit. All dentists were informed
      before submitting the forms that the data might be used for scientific purposes.
      The criteria for Pain Syndrome Dysfunction were used as inclusion criteria. A
      visual analogue scale (VAS) was used to assess the pain intensity before and
      after acupuncture treatment. The acupuncture points and technique used were
      recorded for each treatment. RESULTS: A total number of 70 case reports were
      received. Ten patients were excluded, as they did not fulfil the criteria. The
      remaining 60 patients (50 female) fulfilled an average of 3.2 of the Pain
      Syndrome Dysfunction criteria, out of a possible five. Their mean age was 40.6
      years (range 14-68). The average duration of temporomandibular dysfunction was 32
      months (range 1-180). The patients received a mean of 3.4 treatments, each
      treatment lasting on average 12 minutes. The dentists used only manual
      stimulation, and mainly acupuncture points over the temporomandibular joint and
      in the masticatory muscles, points on the neck, and additional relaxing points.
      The mean pain scores were 7.35 (SD 1.52) before treatment and 2.67 (SD 0.58)
      after treatment (P < 0.001). A beneficial effect was observed in 85% with an
      average reduction in the pain intensity of 75%. CONCLUSION: This audit shows that
      the results of using acupuncture in the treatment of temporomandibular
      dysfunction in a general dental practice are comparable to those obtained in
      clinical studies in university settings. Also the therapeutic approach of using
      acupuncture is similar. Thus, acupuncture is a simple, relatively safe and
      potentially efficacious and useful technique in the management of
      temporomandibular dysfunction in a general dental practice.

PMID- 16618046
TI  - Acupuncture prior to and at embryo transfer in an assisted conception unit--a
      case series.
AB  - Over a period of three years, acupuncture was offered to patients entering
      assisted reproduction therapy. Acupuncture sessions were given at varying, but
      usually weekly, intervals during the in vitro fertilisation (IVF) cycle, and
      immediately before and after embryo transfer. Twenty two patients (average age
      36.2 years) were treated over a total of 26 IVF cycles and 15 pregnancies were
      achieved, as determined by presence of foetal heartbeat on ultrasound at four
      weeks post embryo transfer. This was a success rate of 57.7% compared with 45.3%
      for patients in the IVF unit not treated with acupuncture (P > 0.05). Relaxing
      effects were noted following acupuncture and it is speculated that this may have
      contributed to the increase in pregnancy rate for the acupuncture group.

PMID- 16618047
TI  - Nystagmus following acupuncture--a case report.
AB  - A 50 year old woman experienced an episode of vertigo and nystagmus about 10
      minutes after receiving her first treatment with acupuncture for shoulder pain.
      The nystagmus was confirmed by several health professionals. She had no previous
      history of nystagmus, and the symptom was not associated with feelings of
      faintness. Her blood pressure was 90/50 at the onset of symptoms but returned to
      normal while the symptoms continued. She recovered spontaneously after about five
      hours. Nystagmus after acupuncture has not been unequivocally reported before,
      though dizziness associated with hypotension is common. In this case the
      association may be coincidental, or a focal neurological response to needling; if
      the latter, then it should be regarded as an unavoidable idiosyncratic reaction.

PMID- 16618048
TI  - Contemporary acupuncture in Canada--the McMaster approach.

PMID- 16618049
TI  - Acupuncture with significant infection, in a 'well' patient.

PMID- 16618050
TI  - Potential unblinding of ART study.

PMID- 16618051
TI  - Addressing the stigma of mental illness: two approaches.

PMID- 16618052
TI  - Poverty and psychiatric disorders: a case for action.

PMID- 16618053
TI  - The subjective experience of people with severe mental illness: a potentially
      crucial piece of the puzzle.
AB  - Over the last two decades there has been growing interest in the subjective
      experiences of persons with severe mental illness (SMI). Despite this interest,
      little research has been carried out to understand whether and how such
      experiences are related to the course of SMI. In addition, few psychotherapeutic
      and rehabilitation interventions have been developed especially for persons with
      SMI that seriously take these persons' subjective experiences into account. In
      the present paper we discuss why the use and investigation of the subjective
      experience of people with SMI has been neglected, and we point out the potential
      importance of this experience. We then review the growing literature that focuses
      on the subjective experience of (1) the illness, (2) the self, and (3) the self
      as influenced by the social context of persons with SMI. Finally, the
      implications of this review for rehabilitation, recovery and research are
      discussed.

PMID- 16618054
TI  - Doron's story.

PMID- 16618056
TI  - What is in a name? Professionals and service users' opinions of the Hebrew terms
      used to name psychiatric disorders and disability.
AB  - OBJECTIVES: Stigma constitutes the hidden burden of mental disorders. Its
      ubiquitous presence may be reinforced by iatrogenic factors, such as the terms
      used to name mental disorders and disability. This preliminary study examines
      opinions with regard to the use of these terms in Hebrew. METHODS: Two samples of
      convenience, mental health professionals (n=330) and service users (n=75), were
      asked to complete a self-administered questionnaire about their respective
      acceptance of the current term in use to name psychiatric disorders and
      disability, as well as their preference for alternative terms that may carry a
      lesser degree of stigma. The distribution of responses was compared within and
      between these two groups. RESULTS: There was consensus in both groups that a
      substantial proportion of service users reject the current term used to name
      mental disorder, mahalat nefesh (disease of the soul). Mental health
      professionals had a statistically significant acceptance of this term compared to
      service users. The term hafra'a nafshit (disorder of the soul) was reported to
      carry a lesser degree of stigma. No specific term was selected by more than a
      third of the respondents to best define disability resulting from a psychiatric
      disorder. CONCLUSION: A case for study and possible subsequent action was
      established by this pilot inquiry.

PMID- 16618055
TI  - In the shadow of schizophrenia: a study of siblings' perceptions.
AB  - BACKGROUND: The study assesses the impact of schizophrenia on non-schizophrenic
      siblings with regard to objective and subjective burden, feelings and degree of
      closeness with sibling, social interaction, coping and sense of meaning in life.
      METHOD: 100 subjects, 52 siblings of schizophrenic patients and 48 comparable
      controls participated in the study and filled out self report questionnaires.
      RESULTS: Findings show that siblings of patients with schizophrenia report more
      intense negative feelings, elevated levels of objective and subjective burden,
      less closeness and more shame than the subjects in the control group.
      LIMITATIONS: The 48 controls did not have a sibling with any sickness, so that
      the findings are not necessarily specific to schizophrenia, and may be relevant
      to siblings of those who suffer from various chronic diseases. Further study
      separating these issues is recommended. CONCLUSIONS: In light of the findings
      that show that some siblings of patients with schizophrenia become "secondary
      victims,' we recommend that siblings of the mentally ill receive more
      professional attention. Information about the illness can help in reducing the
      sense of anxiety and guilt, and somewhat alleviate the sense of shame and stigma.

PMID- 16618057
TI  - A stigmatizating attitude towards psychiatric illnesses is associated with
      narcissistic personality traits.
AB  - This study investigates the personality characteristics of individuals who have
      stigmatizing attitudes towards people with mental illness. MATERIAL AND METHOD:
      700 final-year university students completed the "Dangerousness Scale,' the
      "Affective Reaction Scale" and 88 items of the "Defense Style Questionnaire"
      (DSQ). RESULTS: The results showed that there is a strongly positive correlation
      between the use of narcissistic defenses and the tendency to stigmatize. In
      contrast, those with mature defenses have a strong tendency not to stigmatize.
      CONCLUSIONS: The findings suggest that personality traits should be considered in
      efforts to understand stigmatization.

PMID- 16618058
TI  - Ethical dilemmas in psychotherapy: comparison between patients, therapists and
      laypersons.
AB  - BACKGROUND: The attitudes of patients towards ethical dilemmas in psychotherapy
      have been reported in only a few studies. AIMS OF THE STUDY: We investigated
      whether the attitudes of patients undergoing psychotherapy to confidentiality and
      boundaries are different from those of therapists and laypersons. METHODS:
      Clinical vignettes describing ethical dilemmas of confidentiality and boundaries
      were presented to 103 patients undergoing psychotherapy (patient group), 93
      psychotherapists of different professional backgrounds (professional group), and
      55 staff and students from the fields of law and the humanities (lay group).
      Patients were asked how they think therapists should act in the situations
      presented and therapists were asked how they should behave in such situations.
      RESULTS: In general, the patient group showed a greater tendency to view their
      therapists as breaching confidentiality than the professional and lay groups.
      Regarding boundaries, the majority of psychotherapists were against initiating
      any sexual relationship with current patients, former patients, students or
      supervisees, whereas both patients and laypersons showed a less stringent
      attitude; these differences were statistically significant. The vast majority of
      therapists (96.7%) disapproved of accepting money in advance compared to only
      31.1% in the patients group and 54.4% of the lay group. Analysis of the patients
      group by gender did not reveal any significant relationships. CONCLUSIONS: (1)
      Patients have different ethical codes from therapists and laypersons regarding
      the issues of confidentiality. (2) Patients and lay persons are less strict than
      therapists regarding issues of boundaries.

PMID- 16618059
TI  - Psychiatric inpatients' reactions to the SARS epidemic: an Israeli survey.
AB  - BACKGROUND: The threat of the potential spreading of the SARS epidemic caused
      significant stress to many individuals from non-affected countries. In this
      study, we investigated whether the SARS threat affected the subjective mood and
      behavior of Israeli patients with schizophrenia and compared their reactions with
      those noted in their clinical staff. METHODS: Subjects were evaluated with a
      specially designed questionnaire and a modified form of the Spielberger Scale for
      State Anxiety. RESULTS: As compared to staff, patients had higher scores on the
      Modified Spielberger State Anxiety Scale. However, many responses (e.g.,
      dysphoria) to the SARS threat did not differ from staff. Patients felt more
      protected by the authorities and some perceived the epidemic in a psychotic
      manner. CONCLUSIONS: It seems that patients attempt to reduce the effect of
      external stressors by living in an "autistic bubble" (in which outside threats
      cannot enter) or by denying the significance of these stressors and over
      emphasizing the power of medical authorities to protect them. On the other hand,
      some patients also psychotically interpreted these stressors.

PMID- 16618060
TI  - Translating a single-word items scale with multiple subcomponents--A Hebrew
      translation of the Profile of Mood States.
AB  - BACKGROUND: The purpose of the study was to assess the translation adequacy of a
      Hebrew version of the POMS, and to report the decision-making process of
      overcoming methodological flaws. METHOD: The English version was translated to
      Hebrew by expert team approach. Factor analysis for construct validation was
      predominantly used for assessment, in addition to other techniques: back
      translation, use of bilingual subjects, and correlation with other instruments
      for concurrent validation. RESULTS: The final 28-item Hebrew version has suitable
      psychometric properties. Of the six dimensions on the English version scale, five
      dimensions--"anger," "depression:' "fatigue," "tension" and "vigor"--were found
      comparable to the English version, while "confusion" was deleted. LIMITATIONS:
      The pre-testing was performed on students only. CONCLUSIONS: Although the study
      shows valid psychometric properties, further studies in various populations are
      needed to assess the sensitivity of the scale to diverse manipulations.

PMID- 16618061
TI  - Correlates of intrusive memories and avoidance of memories of the Holocaust.
AB  - Although intrusive memories and avoidance of memories are psychological phenomena
      frequently reported by Holocaust survivors, their correlates have not been
      systematically researched. The present cross-sectional study examined socio
      demographic and health characteristics of elderly Holocaust survivors, as well as
      the survivors' experiences during the Holocaust. In addition, present distress
      related to the Holocaust and fear of dying were examined. Results showed that
      survivors frequently suffered from intrusive memories, but not often from
      avoidance of memories of the Holocaust. Intrusive memories were strongly
      associated with present distress from the Holocaust, as well as with self
      perceived bad health and fear of dying. These findings suggest that intrusive
      memories influence survivors' perceptions of life and change the way in which
      they deal with aging.

PMID- 16618062
TI  - Suicide pact among three young sisters.
AB  - A suicide pact is an agreement between two or more people to kill themselves.
      They represent 0.6-4.0% of all suicides, the vast majority being double suicides.
      We present a triple suicide pact involving three young sisters. Atypical features
      of this case include the number of participants, their young ages, and their good
      health conditions. Similarities to previously reported cases include participants
      having family disturbances, histories of depression and borderline personality.

PMID- 16618063
TI  - Treatment of a suicide attempt through psychodynamic therapy in a 17-year-old boy
      with depression: a case study.
AB  - We report the case of a 17-year-old boy hospitalized after a violent and dramatic
      suicide attempt and the interpretative therapy that helped him overcome his
      depression. His course appeared to be typical of the difficulties encountered by
      clinicians when in charge of a severely depressed teenager, and of the liability
      of therapeutic treatment as the patient failed to improve with two consecutive
      antidepressant trials, and with a first attempted treatment by psychodynamic
      therapy. The present report stresses that: (i) in some cases, prolonged
      hospitalization might be helpful in managing treatment of acute phases; (ii)
      every effort should be made to help a depressed adolescent who attempts suicide
      to verbalize his experiences and give them meaning, whatever the
      psychotherapeutic technique. In the case of a suicide attempt with a staged
      component, the psychodynamic approach appears to be an interesting option as it
      may help the patient understand his pathological behavior as if it were a dream.

PMID- 16618064
TI  - Weight of subjectivity in military torts.

PMID- 16618065
TI  - PbR suspension looms for SHAs that can't balance the books.

PMID- 16618066
TI  - Dental contract. Error leaves PCTs in OOH lurch.

PMID- 16618067
TI  - Dental services. Not much to smile about.

PMID- 16618068
TI  - Opinion. On life after crisp.

PMID- 16618069
TI  - No sweet talk on finance fudge. Interview by Nick Edwards.

PMID- 16618070
TI  - Barometer. Public health Feb 2006.

PMID- 16618071
TI  - Mental health. Body of evidence.

PMID- 16618072
TI  - Organisational development. Follow my leader.
AB  - There is going to be a huge shift in leadership style and culture, and a more
      'business-like' approach to working practices will be demanded. Jobs are starting
      to cover entire networks and systems, not single institutions. Organisational
      development means a shift away from short-term targets to improving services
      overall.

PMID- 16618073
TI  - Workforce development. Deep impact.
AB  - To be effective, the DoH's 10 high-impact changes for HR will require engagement
      from all NHS managers. The changes are the culmination of years of strategy
      development in NHS staffing issues. The changes will form a key plank of the
      wider health service efficiency agenda in coming years.

PMID- 16618074
TI  - Personal development. Skills to pay the bills.
AB  - Middle managers will need to develop a wide range of previously uncalled-for
      skills to cope in the new NHS. These include analysing information, examining
      patient flows and making business cases for investment. As commissioners,
      managers will also require skills contract management, service-level agreements
      and dealing with the private sector.

PMID- 16618075
TI  - Career development. The great escape.
AB  - The healthcare outside hospitals white paper is part of a continuing drive to
      involve non-NHS bodies in patient care. This means an unfamiliar working
      environment for migrating managers; with different motivations, less job security
      and increased entrepreneurial freedom. Managers in Partnership has called on
      managers to develop self-marketing skills to suit the new job market.

PMID- 16618076
TI  - People management. Under pressure.
AB  - An HSJ survey of 300 managers found over half feel stressed and 38 per cent have
      been bullied in the last year. Managers should focus on their purpose, and search
      for solutions to the pressures, says one chief executive. Managers have reported
      that work on diversity is under threat because of growing cost pressures and job
      cuts.

PMID- 16618077
TI  - Employment legislation. Rewriting the rulebook.
AB  - NHS organisation will have to be on their toes to keep abreast of a raft of
      recent and forthcoming changes to employment law and discrimination legislation.
      The legislation most affecting NHS middle managers will be implementation of the
      Age Discrimination Act and amendments to the Disability Discrimination Act. The
      CIPD has produced guidelines to help trusts cope with new legislation.

PMID- 16618078
TI  - Cuts loom as DoH struggles to fill pounds sterling 2bn gap in central funds.

PMID- 16618079
TI  - Anger as 'transitional' chiefs named.

PMID- 16618080
TI  - Hospital reform. Why the district general has to learn new tricks to survive.

PMID- 16618081
TI  - What trusts must do now.

PMID- 16618083
TI  - Performance management. Measure and improve your work.

PMID- 16618082
TI  - Data briefing. Length of stay--the day-case drive.

PMID- 16618084
TI  - A brief history. Heading for a half century.
AB  - The history of NHS management can be viewed as five milestones of reorganisation.
      The trend of managers being more concerned with patient care started with the
      1983 Griffiths inquiry. Leaders from other industries came into the NHS but many
      underestimated the job and failed. Stress makes many current chief executive
      posts hard to fill.

PMID- 16618085
TI  - Looking back. Past notes.

PMID- 16618086
TI  - Trainee experiences. Then and now.

PMID- 16618087
TI  - Finance and HR. Special delivery.

PMID- 16618088
TI  - Shared services. Outsourcing. Share option.
AB  - Last April the DoH launched NHS Shared Business Services, a joint venture between
      the DoH and private firm Xansa. SBS guarantees an initial cost saving of 20 per
      cent, and organisations have found it improves procurement and management. Some
      organisations have had difficulties with SBS, finding the migration complex and
      time-consuming.

PMID- 16618089
TI  - Shared services. Good practice. Back-office breakthroughs.

PMID- 16618090
TI  - The chemistry of life's origin: a carbonaceous meteorite perspective.
AB  - Carbonaceous chondrite meteorites are primitive asteroidal fragments that contain
      organic carbon and offer a glimpse of the abiotic chemical processes that
      preceded the onset of life. Their organic material displays structures as diverse
      as kerogen-like macromolecules and simpler soluble compounds that range from
      polar amino acids and polyols to nonpolar hydrocarbons. Several of these
      compounds have identical counterparts in terrestrial biomolecules and some of the
      amino acids show a unique l-asymmetry, suggesting their possible contribution to
      terrestrial molecular evolution and the origin of biological homochirality.

PMID- 16618091
TI  - Inorganic nanotubes: a novel platform for nanofluidics.
AB  - Templating approaches are being developed for the synthesis of inorganic
      nanotubes, a novel platform for nanofluidics. Single crystalline semiconductor
      GaN nanotubes have been synthesized using an epitaxial casting method. The
      partial thermal oxidation of silicon nanowires leads to the synthesis of silica
      nanotubes. The dimension of these nanotubes can be precisely controlled during
      the templating process. These inorganic nanotubes can be integrated into metal
      oxide solution field effect transistors (MOSolFETs), which exhibit rapid field
      effect modulation of ionic conductance. These nanofluidic devices have been
      further demonstrated to be useful for single-molecule sensing, as single DNA
      molecules can be readily detected either by charge effect or by geometry effect.
      These inorganic nanotubes will have great implications in subfemtoliter
      analytical technology and large-scale nanofluidic integration.

PMID- 16618092
TI  - Large-area nanoscale patterning: chemistry meets fabrication.
AB  - This Account describes a new paradigm for large-area nanoscale patterning that
      combines bottom-up and top-down approaches, merging chemistry with fabrication.
      This hybrid strategy uses simple nanofabrication techniques to control the
      alignment, size, shape, and periodicity of nanopatterns and chemical methods to
      control their materials properties and crystallinity. These tools are highly
      flexible and can create surface-patterned nanostructures with unusual properties
      and free-standing nanostructures that are multifunctional and monodisperse. The
      unprecedented scientific and technological opportunities enabled by nanoscale
      patterning over wafer-sized areas are discussed.

PMID- 16618093
TI  - Stereoelectronic substituent effects.
AB  - An investigation was carried out on the influence of the stereochemistry of
      substituents, particularly hydroxyl groups, on their electronic effects in
      piperidines, carbohydrates (pyranosides), and related compounds. Polar groups,
      such as OH, OR, and F, were found in the 3 and 4 position to be much more
      electron-withdrawing when positioned equatorially rather than axially. In
      contrast, little difference in electronic effects was observed from apolar groups
      as a result of epimerization. These observations were believed to be caused by
      differences in charge-dipole interactions and were used to explain why
      stereoisomeric glycosides hydrolyze with different rates. The conformational
      changes of hydroxylated piperidines and related compounds as a function of pH
      were likewise explained from the different substituent effects of axial and
      equatorial OH groups.

PMID- 16618094
TI  - Diazirines: carbene precursors par excellence.
AB  - Diazirines are prime precursors for carbenes. In this Account, we discuss the
      synthetic and mechanistic dimensions that govern the range, availability, and
      utility of diazirines. We focus on the Graham reaction, which affords
      halodiazirines from amidines in a one-pot procedure, and the diazirine exchange
      reaction, which allows easy replacement of an initial diazirine's halo
      substituent by a variety of other nucleophiles. Together, the Graham reaction and
      the diazirine exchange reaction provide an extraordinarily wide range of
      diazirine precurors for electrophilic, ambiphilic, and nucleophilic carbenes.

PMID- 16618095
TI  - Toward improved catalytic low-temperature NOx removal in diesel-powered vehicles.
AB  - The potential of different catalytic after treatment techniques to meet future
      diesel emission standards, which are strongly shifted toward urban driving
      conditions including cold start, are critically discussed in this Account and
      evaluated for their suitability for commercial applications. The dominating
      techniques in this field are NO(x) storage, urea-selective catalytic reduction
      (SCR), and HC-SCR. Each of these techniques have significant disadvantages such
      as sulfur sensitiveness and regeneration requirements of NO(x)-storage materials,
      infrastructure issues and formation of ammonium nitrate (at low temperatures) for
      urea-SCR, and low-temperature activity of HC-SCR catalysts. Ways to overcome
      these disadvantages in commercial applications may involve optimized regeneration
      strategies, reactor modifications, flow reversal, closed-loop NO(x) feedback
      systems, nonthermal plasma, and/or hydrogen-assisted catalyses, etc.

PMID- 16618096
TI  - Is competition between Li+ and Mg2+ the underlying theme in the proposed
      mechanisms for the pharmacological action of lithium salts in bipolar disorder?
AB  - Lithium salts have been in use for the treatment of bipolar disorder for more
      than 50 years, but their pharmacological mode of action remains a matter of
      conjecture. Li(+) and Mg(2+) share many physicochemical properties. Not
      surprisingly, many reported cellular targets for Li(+) action involve Mg(2+)
      activated enzymes, which are inhibited by Li(+). In this Account, we describe
      results from our and other laboratories that suggest that a competition mechanism
      between Li(+) and Mg(2+) ions for Mg(2+)-binding sites in cellular components is
      the underlying theme in putative mechanisms of Li(+) action.

PMID- 16618097
TI  - Synergistic, random sequential binding of substrates in cobalamin-independent
      methionine synthase.
AB  - Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of the N5
      methyl group of methyltetrahydrofolate (CH(3)-H(4)folate) to the sulfur of
      homocysteine (Hcy) to form methionine and tetrahydrofolate (H(4)folate) as
      products. This reaction is thought to involve a direct methyl transfer from one
      substrate to the other, requiring the two substrates to interact in a ternary
      complex. The crystal structure of a MetE.CH(3)-H(4)folate binary complex shows
      that the methyl group is pointing away from the Hcy binding site and is quite
      distant from the position where the sulfur of Hcy would be, raising the
      possibility that this binary complex is nonproductive. The CH(3)-H(4)folate must
      either rearrange or dissociate before methyl transfer can occur. Therefore,
      determining the order of substrate binding is of interest. We have used kinetic
      and equilibrium measurements in addition to isotope trapping experiments to
      elucidate the kinetic pathway of substrate binding in MetE. These studies
      demonstrate that both substrate binary complexes are chemically and kinetically
      competent for methyl transfer and suggest that the conformation observed in the
      crystal structure is indeed on-pathway. Additionally, the substrates are shown to
      bind synergistically, with each substrate binding 30-fold more tightly in the
      presence of the other. Methyl transfer has been determined to be slow compared to
      ternary complex formation and dissociation. Simulations indicate that nearly all
      of the enzyme is present as the ternary complex under physiological conditions.

PMID- 16618098
TI  - Activation of methyltetrahydrofolate by cobalamin-independent methionine
      synthase.
AB  - Cobalamin-independent methionine synthase (MetE) catalyzes the final step of de
      novo methionine synthesis using the triglutamate derivative of
      methyltetrahydrofolate (CH(3)-H(4)PteGlu(3)) as methyl donor and homocysteine
      (Hcy) as methyl acceptor. This reaction is challenging because at physiological
      pH the Hcy thiol is not a strong nucleophile and CH(3)-H(4)PteGlu(3) provides a
      very poor leaving group. Our laboratory has previously established that Hcy is
      ligated to a tightly bound zinc ion in the MetE active site. This interaction
      activates Hcy by lowering its pK(a), such that the thiolate is stabilized at
      neutral pH. The remaining chemical challenge is the activation of CH(3)
      H(4)PteGlu(3). Protonation of N5 of CH(3)-H(4)PteGlu(3) would produce a better
      leaving group, but occurs with a pK(a) of 5 in solution. We have taken advantage
      of the sensitivity of the CH(3)-H(4)PteGlu(3) absorption spectrum to probe its
      protonation state when bound to MetE. Comparison of free and MetE-bound CH(3)
      H(4)PteGlu(3) absorbance spectra indicated that the N5 is not protonated in the
      binary complex. Rapid reaction studies have revealed changes in CH(3)
      H(4)PteGlu(3) absorbance that are consistent with protonation at N5. These
      absorbance changes show saturable dependence on both Hcy and CH(3)-H(4)PteGlu(3),
      indicating that protonation of CH(3)-H(4)PteGlu(3) occurs upon formation of the
      ternary complex and prior to methyl transfer. Furthermore, the tetrahydrofolate
      (H(4)PteGlu(3)) product appears to remain bound to MetE, and in the presence of
      excess Hcy a MetE.H(4)PteGlu(3).Hcy mixed ternary complex forms, in which
      H(4)PteGlu(3) is protonated.

PMID- 16618099
TI  - Crystal structures of the short-chain flavin reductase HpaC from Sulfolobus
      tokodaii strain 7 in its three states: NAD(P)(+)(-)free, NAD(+)(-)bound, and
      NADP(+)(-)bound.
AB  - 4-Hydroxyphenylacetate (4-HPA) is oxidized as an energy source by two component
      enzymes, the large component (HpaB) and the small component (HpaC). HpaB is a 4
      HPA monooxygenase that utilizes FADH(2) supplied by a flavin reductase HpaC. We
      determined the crystal structure of HpaC (ST0723) from the aerobic
      thermoacidophilic crenarchaeon Sulfolobus tokodaii strain 7 in its three states
      [NAD(P)(+)-free, NAD(+)-bound, and NADP(+)-bound]. HpaC exists as a homodimer,
      and each monomer was found to contain an FMN. HpaC preferred FMN to FAD because
      there was not enough space to accommodate the AMP moiety of FAD in its flavin
      binding site. The most striking difference between the NAD(P)(+)-free and the
      NAD(+)/NADP(+)-bound structures was observed in the N-terminal helix. The N
      terminal helices in the NAD(+)/NADP(+)-bound structures rotated ca. 20 degrees
      relative to the NAD(P)(+)-free structure. The bound NAD(+) has a compact folded
      conformation with nearly parallel stacking rings of nicotinamide and adenine. The
      nicotinamide of NAD(+) stacked the isoalloxazine ring of FMN so that NADH could
      directly transfer hydride. The bound NADP(+) also had a compact conformation but
      was bound in a reverse direction, which was not suitable for hydride transfer.

PMID- 16618100
TI  - Molten globule formation in apomyoglobin monitored by the fluorescent probe Nile
      Red.
AB  - The interaction of nile red (NR) with apomyoglobin (ApoMb) in the native (pH 7)
      and molten globule (pH 4) states was investigated using experimental and
      computational methods. NR binds to hydrophobic locations in ApoMb with higher
      affinity (K(d) = 25 +/- 5 microM) in the native state than in the molten globule
      state (K(d) = 52 +/- 5 microM). In the molten globule state, NR is located in a
      more hydrophobic environment. The dye does not bind to the holoprotein,
      suggesting that the binding site is located at the heme pocket. In addition to
      monitoring steady-state properties, the fluorescence emission of NR is capable of
      tracking submillisecond, time-resolved structural rearrangements of the protein,
      induced by a nanosecond pH jump. Molecular dynamics simulations were run on ApoMb
      at neutral pH and at pH 4. The structure obtained for the molten globule state is
      consistent with the experimentally available structural data. The docking of NR
      with the crystal structure shows that the ligand binds into the binding pocket of
      the heme group, with an orientation bringing the planar ring system of NR to
      overlap with the position of two of the heme porphyrin rings in Mb. The docking
      of NR with the ApoMb structure at pH 4 shows that the dye binds to the heme
      pocket with a slightly less favorable binding energy, in keeping with the
      experimental K(d) value. Under these conditions, NR is positioned in a different
      orientation, reaching a more hydrophobic environment in agreement with the
      spectroscopic data.

PMID- 16618101
TI  - Affinity, kinetic, and structural study of the interaction of 3-O
      sulfotransferase isoform 1 with heparan sulfate.
AB  - The 3-O-sulfonation of glucosamine residues in heparan sulfate (HS) by 3-O
      sulfotransferase (3-OST) is a key substitution that is present in HS sequences of
      biological importance, in particular HS anticoagulant activity. Six different
      isoforms of 3-OST have been identified that exhibit different substrate
      specificity. In this paper the affinity and kinetics of the interaction between 3
      O-sulfotransferase isoform 1 (3-OST-1) and HS have been examined using surface
      plasmon resonance (SPR). 3-OST-1 binds with micomolar affinity to HS (K(D) = 2.79
      microM), and this interaction is apparently independent of the presence of the
      coenzyme, 3'-phosphoadenosine 5'-phosphosulfate (PAPS). A conformational change
      in the complex has also been detected, supporting data from previous studies.
      Selected 3-OST-1 mutants have provided valuable information of amino acid
      residues that participate in 3-OST-1 interaction with HS substrate and its
      catalytic activity. The results from this study contribute to understanding the
      substrate specificity among the 3-OST isoforms and in the mechanism of 3-OST-1
      catalyzed biosynthesis of anticoagulant HS.

PMID- 16618102
TI  - Anomalous orientation-dependent effective pair interaction among histidine and
      other amino acid residues in metalloproteins: breakdown of the hydropathy scale
      index.
AB  - Hydropathy scale is widely used to obtain a measure of the effective interaction
      between any two amino acid residues in proteins and is based on the assumption
      that attraction between two hydrophobic groups and repulsion between hydrophilic
      groups (in water) can be translated straightforwardly to protein environment.
      Here we employ a recently developed statistical mechanical approach combined with
      the Protein Data Bank to obtain both distance- and orientation-dependent
      potential of mean force (ODPMF). This allowed us to explore effective pair
      potential among many amino acid residues and to examine the validity of the
      hydropathy scale in modeling the interaction among amino acid residues. We find
      that in some cases, like Phe-Phe and Lys-Lys, the hydropathy scale approach is
      largely obeyed. However, we also observe many unexpected pair interactions which
      defy the trend given by published hydropathy scales. An example of the former is
      the arginine-arginine (Arg-Arg) pair interaction which is found to be strongly
      and surprisingly attractive at short separation, even though it is the most
      hydrophilic residue. Here the head-to-head (see text) interaction is also
      stabilized. Tryptophan residues also exhibit strong attractive interaction.
      Equally important, we find strong influence of metal in determining effective
      interaction among the amino acid residues. It is the behavior of the histidine
      (His) which is found to be the most unusual. It exhibits a strong attractive
      interaction with itself which gets significantly enhanced in metalloproteins.
      These results highlight the important (sometime hidden) role of metals in protein
      structure and folding.

PMID- 16618103
TI  - Quaternary structure of carbonmonoxyhemoglobins in solution: structural changes
      induced by the allosteric effector inositol hexaphosphate.
AB  - We have applied the residual dipolar coupling (RDC) method to investigate the
      solution quaternary structures of (2)H- and (15)N-labeled human normal adult
      recombinant hemoglobin (rHb A) and a low-oxygen-affinity mutant recombinant
      hemoglobin, rHb(alpha96Val-->Trp), both in the carbonmonoxy form, in the absence
      and presence of an allosteric effector, inositol hexaphosphate (IHP), using a
      stretched polyacrylamide gel as the alignment medium. Our recent RDC results
      [Lukin, J. A., Kontaxis, G., Simplaceanu, V., Yuan, Y., Bax, A., and Ho, C.
      (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 517-520] indicate that the quaternary
      structure of HbCO A in solution is a dynamic ensemble between two previously
      determined crystal structures, R (crystals grown under high-salt conditions) and
      R2 (crystals grown under low-salt conditions). On the basis of a comparison of
      the geometric coordinates of the T, R, and R2 structures, it has been suggested
      that the oxygenation of Hb A follows the transition pathway from T to R and then
      to R2, with R being the intermediate structure [Srinivasan, R., and Rose, G. D.
      (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 11113-11117]. The results presented here
      suggest that IHP can shift the solution quaternary structure of HbCO A slightly
      toward the R structure. The solution quaternary structure of rHbCO(alpha96Val-
      >Trp) in the absence of IHP is similar to that of HbCO A in the presence of IHP,
      consistent with rHbCO(alpha96Val-->Trp) having an affinity for oxygen lower than
      that of Hb A. Moreover, IHP has a much stronger effect in shifting the solution
      quaternary structure of rHbCO(alpha96Val-->Trp) toward the R structure and toward
      the T structure, consistent with IHP causing a more pronounced decrease in its
      oxygen affinity. The results presented in this work, as well as other results
      recently reported in the literature, clearly indicate that there are multiple
      quaternary structures for the ligated form of hemoglobin. These results also
      provide new insights regarding the roles of allosteric effectors in regulating
      the structure and function of hemoglobin. The classical two-state/two-structure
      allosteric mechanism for the cooperative oxygenation of hemoglobin cannot account
      for the structural and functional properties of this protein and needs to be
      revised.

PMID- 16618104
TI  - Proposal for a hydrogen bond network in the active site of the prototypic gamma
      class carbonic anhydrase.
AB  - The crystal structure of Cam, the prototypic gamma-class carbonic anhydrase,
      reveals active site residues Gln75, Asn73, and Asn 202 previously hypothesized to
      participate in catalysis. These potential roles were investigated for the first
      time by kinetic analyses of site-specific replacement variants of the zinc and
      cobalt forms of Cam. Gln75 replacement variants showed large decreases in
      k(cat)/K(m) relative to wild-type. Further, the Gln75 variants showed a loss of
      the pK(a) in pH versus k(cat)/K(m) profiles previously attributed to ionization
      of the metal-bound water yielding the hydroxyl group attacking CO(2). These
      results support the previously proposed role for Gln75 in hydrogen bonding with
      the catalytic hydroxyl orienting it for attack on CO(2). Kinetic analyses of
      Asn73 variants were consistent with a role in hydrogen bonding with Gln75 to
      position it for optimal interaction with the catalytic hydroxyl. Kinetic analyses
      of Asn202 variants showed substantial decreases in k(cat)/K(m) relative to the
      wild-type enzyme supporting the previously hypothesized role in polarizing CO(2)
      and facilitating attack from the metal-bound hydroxyl. On the basis of results
      presented here, and previously reported structural analyses, we present a
      catalytic mechanism involving Gln75, Asn73, and Asn202 that also suggests a role
      for Glu62 not previously recognized. Finally, the results suggest that the gamma
      , beta-, and alpha-class carbonic anhydrases each independently evolved
      variations of a fundamental hydrogen bond network essential for catalysis.

PMID- 16618105
TI  - Semisynthesis and characterization of mammalian thioredoxin reductase.
AB  - Thioredoxin reductase and thioredoxin constitute the cellular thioredoxin system,
      which provides reducing equivalents to numerous intracellular target disulfides.
      Mammalian thioredoxin reductase contains the rare amino acid selenocysteine.
      Known as the "21st" amino acid, selenocysteine is inserted into proteins by
      recoding UGA stop codons. Some model eukaryotic organisms lack the ability to
      insert selenocysteine, and prokaryotes have a recoding apparatus different from
      that of eukaryotes, thus making heterologous expression of mammalian
      selenoproteins difficult. Here, we present a semisynthetic method for preparing
      mammalian thioredoxin reductase. This method produces the first 487 amino acids
      of mouse thioredoxin reductase-3 as an intein fusion protein in Escherichia coli
      cells. The missing C-terminal tripeptide containing selenocysteine is then
      ligated to the thioester-tagged protein by expressed protein ligation. The
      semisynthetic version of thioredoxin reductase that we produce in this manner has
      k(cat) values ranging from 1500 to 2220 min(-)(1) toward thioredoxin and has
      strong peroxidase activity, indicating a functional form of the enzyme. We
      produced the semisynthetic thioredoxin reductase with a total yield of 24 mg from
      6 L of E. coli culture (4 mg/L). This method allows production of a fully
      functional, semisynthetic selenoenzyme that is amenable to structure-function
      studies. A second semisynthetic system is also reported that makes use of peptide
      complementation to produce a partially active enzyme. The results of our peptide
      complementation studies reveal that a tetrapeptide that cannot ligate to the
      enzyme (Ac-Gly-Cys-Sec-Gly) can form a noncovalent complex with the truncated
      enzyme to form a weak complex. This noncovalent peptide-enzyme complex has 350
      500-fold lower activity than the semisynthetic enzyme produced by peptide
      ligation.

PMID- 16618106
TI  - Roles for Arg426 and Trp111 in the modulation of NADH oxidase activity of the
      catalase-peroxidase KatG from Burkholderia pseudomallei inferred from pH-induced
      structural changes.
AB  - Crystals of Burkholderia pseudomallei KatG retain their ability to diffract X
      rays at high resolution after adjustment of the pH from 5.6 to 4.5, 6.5, 7.5, and
      8.5, providing a unique view of the effect of pH on protein structure. One
      significant pH-sensitive change lies in the appearance of a perhydroxy group
      attached to the indole nitrogen of the active site Trp111 above pH 7, similar to
      a modification originally observed in the Ser324Thr variant of the enzyme at pH
      5.6. The modification forms rapidly from molecular oxygen in the buffer with 100%
      occupancy after one minute of soaking of the crystal at room temperature and pH
      8.5. The low temperature (4 K) ferric EPR spectra of the resting enzyme, being
      very sensitive to changes in the heme iron microenvironment, confirm the presence
      of the modification above pH 7 in native enzyme and variants lacking Arg426 or
      Met264 and its absence in variants lacking Trp111 or Tyr238. The indole
      perhydroxy group is very likely the reactive intermediate of molecular oxygen in
      the NADH oxidase reaction, and Arg426 is required for its reduction. The second
      significant pH-sensitive change involves the buried side chain of Arg426 that
      changes from one predominant conformation at low pH to a second at high pH. The
      pH profiles of the peroxidase, catalase, and NADH oxidase reactions can be
      correlated with the distribution of Arg426 conformations. Other pH-induced
      structural changes include a number of surface-situated side chains, but there is
      only one change involving a displacement of main chain atoms triggered by the
      protonation of His53 in a deep pocket in the vicinity of the molecular 2-fold
      axis.

PMID- 16618107
TI  - Bacteriophage lambda gpNu1 and Escherichia coli IHF proteins cooperatively bind
      and bend viral DNA: implications for the assembly of a genome-packaging motor.
AB  - Terminase enzymes are common to both prokaryotic and eukaryotic double-stranded
      DNA viruses and are responsible for packaging viral DNA into the confines of an
      empty procapsid shell. In all known cases, the holoenzymes are heteroligomers
      composed of a large subunit that possesses the catalytic activities required for
      genome packaging and a small subunit that is responsible for specific recognition
      of viral DNA. In bacteriophage lambda, the DNA recognition protein is gpNu1. The
      gpNu1 subunit interacts with multiple recognition elements within cos, the
      packaging initiation site in viral DNA, to site-specifically assemble the
      packaging machinery. Motor assembly is modulated by the Escherichia coli
      integration host factor protein (IHF), which binds to a consensus sequence also
      located within cos. On the basis of a variety of biochemical data and the
      recently solved NMR structure of the DNA binding domain of gpNu1, we proposed a
      novel DNA binding mode that predicts significant bending of duplex DNA by gpNu1
      (de Beer et al. (2002) Mol. Cell 9, 981-991). We further proposed that gpNu1 and
      IHF cooperatively bind and bend viral DNA to regulate the assembly of the
      packaging motor. Here, we characterize cooperative gpNu1 and IHF binding to the
      cos site in lambda DNA using a quantitative electrophoretic mobility shift (EMS)
      assay. These studies provide direct experimental support for the long presumed
      cooperative assembly of gpNu1 and IHF at the cos sequence of lambda DNA. Further,
      circular permutation experiments demonstrate that the viral and host proteins
      each introduce a strong bend in cos-containing DNA, but not nonspecific DNA
      substrates. Thus, specific recognition of viral DNA by the packaging apparatus is
      mediated by both DNA sequence information and by structural alteration of the
      duplex. The relevance of these results with respect to the assembly of a viral
      DNA-packaging motor is discussed.

PMID- 16618109
TI  - Characterization of human saposins by NMR spectroscopy.
AB  - Saposins are lipid-binding and membrane-perturbing glycoproteins of the mammalian
      lysosomes involved in sphingolipid and membrane digestion. Although the four
      human saposins (Saps), A-D, are sequence-related, they are responsible for the
      activation of different steps in the cascade of lysosomal glycosphingolipid
      degradation. Saposin activity is maximal under acidic conditions, and the pH
      dependence of lipid and membrane binding has been assigned to conformational
      variability. We have employed solution NMR spectroscopy to all four (15)N-labeled
      human saposins at both neutral and acidic pH. Using backbone NOEs and residual
      dipolar couplings, the "saposin fold" comprising five alpha-helices was confirmed
      for Sap-A, Sap-C, and Sap-D. Structural variations within these proteins are in
      the order of variations between the known structures of Sap-C and NK-lysin. In
      contrast, Sap-B yielded spectra of very poor quality, presumably due to
      conformational heterogeneity and molecular association. Sap-D exists in a slow
      dynamic equilibrium of two conformational states with yet unknown function. At pH
      4.0, where all saposins are highly unstable, Sap-C undergoes a transition to a
      specific dimeric state, which is likely to resemble the structure recently found
      in both Sap-C in a detergent environment and crystals of Sap-B.

PMID- 16618108
TI  - Effects of monovalent anions on a temperature-dependent heat capacity change for
      Escherichia coli SSB tetramer binding to single-stranded DNA.
AB  - We have previously shown that the linkage of temperature-dependent protonation
      and DNA base unstacking equilibria contribute significantly to both the negative
      enthalpy change (DeltaH(obs)) and the negative heat capacity change
      (DeltaC(p,obs)) for Escherichia coli SSB homotetramer binding to single-stranded
      (ss) DNA. Using isothermal titration calorimetry we have now examined DeltaH(obs)
      over a much wider temperature range (5-60 degrees C) and as a function of
      monovalent salt concentration and type for SSB binding to (dT)(70) under solution
      conditions that favor the fully wrapped (SSB)(65) complex (monovalent salt
      concentration >or=0.20 M). Over this wider temperature range we observe a
      strongly temperature-dependent DeltaC(p,obs). The DeltaH(obs) decreases as
      temperature increases from 5 to 35 degrees C (DeltaC(p,obs) <0) but then
      increases at higher temperatures up to 60 degrees C (DeltaC(p,obs) >0). Both salt
      concentration and anion type have large effects on DeltaH(obs) and DeltaC(p,obs).
      These observations can be explained by a model in which SSB protein can undergo a
      temperature- and salt-dependent conformational transition (below 35 degrees C),
      the midpoint of which shifts to higher temperature (above 35 degrees C) for SSB
      bound to ssDNA. Anions bind weakly to free SSB, with the preference Br(-) > Cl(-)
      > F(-), and these anions are then released upon binding ssDNA, affecting both
      DeltaH(obs) and DeltaC(p,obs). We conclude that the experimentally measured
      values of DeltaC(p,obs) for SSB binding to ssDNA cannot be explained solely on
      the basis of changes in accessible surface area (ASA) upon complex formation but
      rather result from a series of temperature-dependent equilibria (ion binding,
      protonation, and protein conformational changes) that are coupled to the SSB
      ssDNA binding equilibrium. This is also likely true for many other protein
      nucleic acid interactions.

PMID- 16618111
TI  - Invariant chain transmembrane domain trimerization: a step in MHC class II
      assembly.
AB  - The transmembrane (TM) domain of the major histocompatibility complex (MHC) class
      II-associated invariant chain (Ii) has long been implicated in both correct
      folding and function of the MHC class II complex. To function correctly, Ii must
      form a trimer, and the TM domain is one of the domains thought to stabilize the
      trimeric state. Specific mutations in the TM domain have been shown previously to
      disrupt MHC class II functions such as mature complex formation and antigen
      presentation, possibly due to disruption of Ii TM helix-helix interactions.
      Although this hypothesis has been reported several times in the literature, thus
      far no experimental measurements have been made to explore the relationship
      between TM domain structure and TM mutations that affect Ii function. We have
      applied biophysical and computational methods to study the folding and assembly
      of the Ii TM domain in isolation and find that the TM domain strongly self
      associates. According to analytical ultracentrifugation analyses, the primary
      oligomeric state for this TM domain is a strongly associated trimer with a
      dissociation constant of approximately 120 nM in DPC micelles. We have also
      examined the effect of functionally important mutations of glutamine and
      threonine residues in the TM domain on its structure, providing results that now
      link the disruption of TM helix interactions to previously reported losses of Ii
      function.

PMID- 16618110
TI  - Solution structures of spinach acyl carrier protein with decanoate and stearate.
AB  - Acyl carrier protein (ACP) is a cofactor in a variety of biosynthetic pathways,
      including fatty acid metabolism. Thus, it is of interest to determine structures
      of physiologically relevant ACP-fatty acid complexes. We report here the NMR
      solution structures of spinach ACP with decanoate (10:0-ACP) and stearate (18:0
      ACP) attached to the 4'-phosphopantetheine prosthetic group. The protein in the
      fatty acid complexes adopts a single conformer, unlike apo- and holo-ACP, which
      interconvert in solution between two major conformers. The protein component of
      both 10:0- and 18:0-ACP adopts the four-helix bundle topology characteristic of
      ACP, and a fatty acid binding cavity was identified in both structures. Portions
      of the protein close in space to the fatty acid and the 4'-phosphopantetheine
      were identified using filtered/edited NOESY experiments. A docking protocol was
      used to generate protein structures containing bound fatty acid for 10:0- and
      18:0-ACP. In both cases, the predominant structure contained fatty acid bound
      down the center of the helical bundle, in agreement with the location of the
      fatty acid binding pockets. These structures demonstrate the conformational
      flexibility of spinach ACP and suggest how the protein changes to accommodate its
      myriad binding partners.

PMID- 16618112
TI  - Structures of Staphylococcus aureus cell-wall complexes with vancomycin,
      eremomycin, and chloroeremomycin derivatives by 13C{19F} and 15N{19F} rotational
      echo double resonance.
AB  - Solid-state NMR has been used to examine isolated cell walls and intact whole
      cells of Staphylococcus aureus complexed to five different vancomycin,
      eremomycin, and chloroeremomycin derivatives. The cell walls and whole cells were
      specifically labeled with d-[1-(13)C]alanine, or a combination of [1
      (13)C]glycine and [epsilon-(15)N]lysine. Each of the bound glycopeptides had a
      (19)F-labeled substituent at either its C-terminus or its disaccharide position.
      The (13)C{(19)F} rotational-echo double-resonance (REDOR) dephasing for the cell
      wall (13)C-labeled bridging pentaglycyl segment connecting a glycopeptide
      complexed peptidoglycan stem with its neighboring stem indicates that the
      fluorine labels for all bound glycopeptides are positioned at one or the other
      end of the bridge. An exception is N'-(p-trifluoromethoxybenzyl)chloroeremomycin,
      whose hydrophobic substituent differs in length by one phenyl group compared to
      that of oritavancin, N'-4-[(4-chlorophenyl)benzyl)]chloroeremomycin. For this
      drug, the fluorine label is near the middle of the pentaglycyl segment.
      (15)N{(19)F} REDOR dephasing shows the proximity of the fluorine to the bridge
      link site of the pentaglycyl bridge for C-terminus-substituted moieties and the
      cross-link site for disaccharide-substituted moieties. Full-echo REDOR spectra of
      cell-wall complexes from cells labeled by d-[1-(13)C]alanine (in the presence of
      an alanine racemase inhibitor) reveal three different carbonyl carbon chemical
      shift environments, arising from the d-Ala-d-Ala binding site and the d-Ala-Gly-1
      cross-link site. The REDOR results indicate a single fluorine dephasing center in
      each peptidoglycan complex. Molecular models of the mature cell-wall complexes
      that are consistent with internuclear distances obtained from (13)C{(19)F} and
      (15)N{(19)F} REDOR dephasing allow a correlation of structure and antimicrobial
      activity of the glycopeptides.

PMID- 16618113
TI  - Mutational studies of G553 in TM5 of ABCG2: a residue potentially involved in
      dimerization.
AB  - ABCG2 is an ATP-binding cassette half-transporter conferring resistance to
      chemotherapeutic agents such as mitoxantrone, irinotecan, and flavopiridol. With
      its one transmembrane and one ATP-binding domain, ABCG2 is thought to
      homodimerize for function. One conserved region potentially involved in
      dimerization is a three-amino acid sequence in transmembrane segment 5 (residues
      552-554). Mutations in the corresponding residues in the Drosophila white protein
      (an orthologue of ABCG2) are thought to disrupt heterodimerization. We
      substituted glycine 553 with leucine (G553L) followed by stable transfection in
      HEK 293 cells. The mutant was not detectable on the cell surface, and markedly
      reduced protein expression levels were observed by immunoblotting. A deficiency
      in N-linked glycosylation was suggested by a reduction in molecular mass compared
      to that of the 72 kDa wild-type ABCG2. Similar results were observed with the
      G553E mutant. Confocal microscopy demonstrated mostly ER localization of the
      G553L mutant in HEK 293 cells, even when coexpressed with the wild-type protein.
      Despite its altered localization, the G553L and G553E mutants were cross-linked
      using amine-reactive cross-linkers with multiple arm lengths, suggesting that the
      monomers are in the proximity of each other but are unable to complete normal
      trafficking. Interestingly, when expressed in Sf9 insect cells, G553L moves to
      the cell membrane but is unable to hydrolyze ATP or transport the Hoechst dye.
      Still, when coexpressed, the mutant interferes with the Hoechst transport
      activity of the wild-type protein. These data show that glycine 553 is important
      for protein trafficking and are consistent with, but do not yet prove, its
      involvement in ABCG2 homodimerization.

PMID- 16618114
TI  - Conformational changes in sarcoplasmic reticulum Ca(2+)-ATPase mutants: effect of
      mutations either at Ca(2+)-binding site II or at tryptophan 552 in the cytosolic
      domain.
AB  - By analyzing, after expression in yeast and purification, the intrinsic
      fluorescence properties of point mutants of rabbit Ca(2+)-ATPase (SERCA1a) with
      alterations to amino acid residues in Ca(2+)-binding site I (E(771)), site II
      (E(309)), in both sites (D(800)), or in the nucleotide-binding domain (W(552)),
      we were able to follow the conformational changes associated with various steps
      in the ATPase catalytic cycle. Whereas Ca(2+) binding to purified wild-type (WT)
      ATPase in the absence of ATP leads to the rise in Trp fluorescence expected for
      the so-called E2 --> E1Ca(2) transition, the Ca(2+)-induced fluorescence rise is
      dramatically reduced for the E(309)Q mutant. As this purified E(309)Q mutant
      retains the ability to bind Ca(2+) at site I (but not at site II), we tentatively
      conclude that the protein reorganization induced by Ca(2+) binding at site II
      makes the major contribution to the overall Trp fluorescence changes observed
      upon Ca(2+) binding to both sites. Judging from the fluorescence response of
      W(552)F, similar to that of WT, these changes appear to be primarily due to
      membranous tryptophans, not to W(552). The same holds for the fluorescence rise
      observed upon phosphorylation from P(i) (the so-called E2 --> E2P transition). As
      for WT ATPase, Mg(2+) binding in the absence of Ca(2+) affects the fluorescence
      of the E(309)Q mutant, suggesting that this Mg(2+)-dependent fluorescence rise
      does not reflect binding of Mg(2+) to Ca(2+) sites; instead, Mg(2+) probably
      binds close to the catalytic site, or perhaps near transmembrane span M3, at a
      location recently revealed by Fe(2+)-catalyzed oxidative cleavage. Mutation of
      W(552) hardly affects ATP-induced fluorescence changes in the absence of Ca(2+),
      which are therefore mostly due to membranous Trp residues, demonstrating long
      range communication between the nucleotide-binding domain and the membranous
      domain.

PMID- 16618115
TI  - Interaction of the indole class of vacuolar H(+)-ATPase inhibitors with lipid
      bilayers.
AB  - The selective inhibitor of osteoclastic V-ATPase (2Z,4E)-5-(5,6-dichloro-2
      indolyl)-2-methoxy-N-(1,2,2,6,6-pentamethylpiperidin-4-yl)-2,4-pentadienamide (SB
      242784), member of the indole class of V-ATPase inhibitors, is expected to target
      the membrane-bound domain of the enzyme. A structural study of the interaction of
      this inhibitor with the lipidic environment is an essential step in the
      understanding of the mechanism of inhibition. In this work, a comprehensive study
      of the relevant features of this interaction was performed. Inhibitor partition
      coefficients to lipid vesicles as well as its transverse location, orientation
      (order parameters), and dynamics while bound to bilayers were determined through
      photophysical techniques, taking advantage of the intrinsic fluorescence of the
      molecule. To better evaluate the functionally relevant features of SB 242784, a
      second inhibitor, INH-1, from the same class and having a reduced activity was
      also examined. It is shown that regarding membrane interaction their properties
      remain very similar for both molecules, suggesting that the differences in
      inhibition efficiencies are solely a consequence of the molecular recognition
      processes within the inhibition site in the V-ATPase.

PMID- 16618116
TI  - Phosphorylation of a single head of smooth muscle myosin activates the whole
      molecule.
AB  - Regulatory light chain (RLC) phosphorylation activates smooth and non-muscle
      myosin II, but it has not been established if phosphorylation of one head turns
      on the whole molecule. Baculovirus expression and affinity chromatography were
      used to isolate heavy meromyosin (HMM) containing one phosphorylated and one
      dephosphorylated RLC (1-P HMM). Motility and steady-state ATPase assays indicated
      that 1-P HMM is nearly as active as HMM with two phosphorylated heads (2-P HMM).
      Single-turnover experiments further showed that both the dephosphorylated and
      phosphorylated heads of 1-P HMM can be activated by actin. Singly phosphorylated
      full-length myosin was also an active species with two cycling heads. Our results
      suggest that phosphorylation of one RLC abolishes the asymmetric inhibited state
      formed by dephosphorylated myosin [Liu, J., et al. (2003) J. Mol. Biol. 329, 963
      972], allowing activation of both the phosphorylated and dephosphorylated heads.
      These findings help explain how smooth muscles are able to generate high levels
      of stress with low phosphorylation levels.

PMID- 16618117
TI  - Functional studies of the MACPF domain of human complement protein C8alpha reveal
      sites for simultaneous binding of C8beta, C8gamma, and C9.
AB  - Human C8 is one of five components of the membrane attack complex of complement
      (MAC). It contains three subunits (C8alpha, C8beta, C8gamma) arranged as a
      disulfide-linked C8alpha-gamma dimer that is noncovalently associated with
      C8beta. C8alpha, C8beta, and complement components C6, C7, and C9 form the MAC
      family of proteins. All contain N- and C-terminal modules and an intervening 40
      kDa segment referred to as the membrane attack complex/perforin (MACPF) domain.
      During MAC formation, C8alpha binds and mediates the self-polymerization of C9 to
      form a pore-like structure on target cells. The C9 binding site was previously
      shown to reside within a 52-kDa segment composed of the C8alpha N-terminal
      modules and MACPF domain (alphaMACPF). In the present study, we examined the role
      of the MACPF domain in binding C9. Recombinant alphaMACPF and a disulfide-linked
      alphaMACPF-gamma dimer were successfully produced in Escherichia coli and
      purified. alphaMACPF was shown to simultaneously bind C8beta, C8gamma, and C9 and
      form a noncovalent alphaMACPF.C8beta.C8gamma.C9 complex. Similar results were
      obtained for the recombinant alphaMACPF-gamma dimer. This dimer bound C8beta and
      C9 to form a hemolytically active (alphaMACPF-gamma).C8beta.C9 complex. These
      results indicate that the principal binding site for C9 lies within the MACPF
      domain of C8alpha. They also suggest this site and the binding sites for C8beta
      and C8gamma are distinct. alphaMACPF is the first human MACPF domain to be
      produced recombinantly and in a functional form. Such a result suggests that this
      segment of C8alpha and corresponding segments of the other MAC family members are
      independently folded domains.

PMID- 16618118
TI  - Dysbindin structural homologue CK1BP is an isoform-selective binding partner of
      human casein kinase-1.
AB  - Casein kinase-1 is a family of ubiquitous eukaryotic protein kinases that
      frequently function in tandem with the ubiquitin modification system to modulate
      protein turnover and trafficking. In Alzheimer's disease, these enzymes
      colocalize with ubiquitinated lesions, including neurofibrillary tangles and
      granulovacuolar degeneration bodies, suggesting they also play a role in disease
      pathogenesis. To identify binding partners that potentially regulate or recruit
      these enzymes toward disease lesions, a Sos-recruitment yeast two-hybrid screen
      was performed with human Ckidelta (the casein kinase-1 isoform most closely
      linked to granulovacuolar degeneration bodies) and a human brain cDNA library.
      All interacting clones contained a single open reading frame termed casein kinase
      1 binding protein (CK1BP). On the basis of sequence alignments, CK1BP was a
      structural homologue of the acidic domain of dysbindin, a component of the
      dystrophin-associated protein complex and the biogenesis of lysosome-related
      organelles complex-1. CK1BP interacted with full-length Ckidelta, the isolated
      Ckidelta catalytic domain, Ckigamma2, -gamma3, and -epsilon in the yeast two
      hybrid system, and bound Ckidelta and -epsilon in pulldown assays but did not
      interact with Ckialpha. Interaction with the Ckidelta catalytic domain led to
      concentration-dependent inhibition of protein kinase activity in the presence of
      protein substrates tau and alpha-synuclein. Although intact dysbindin did not
      bind any CK1 isoform, deletion of its coiled-coil domain yielded a protein
      fragment that behaved much like CK1BP in two-hybrid screens. These data suggest
      that the acidic domain of dysbindin and its paralogs in humans may function to
      recruit casein kinase-1 isoforms to protein complexes involved in multiple
      biological functions.

PMID- 16618119
TI  - The two NK-1 binding sites correspond to distinct, independent, and non
      interconvertible receptor conformational states as confirmed by plasmon-waveguide
      resonance spectroscopy.
AB  - Two nonstoichiometric ligand binding sites have been previously reported for the
      NK-1 receptor, with the use of classical methods (radioligand binding and second
      messenger assays). The most populated (major, NK-1M) binding site binds substance
      P (SP) and is related to the adenylyl cyclase pathway. The less populated (minor,
      NK-1m) binding site binds substance P, C-terminal hexa- and heptapeptide
      analogues of SP, and the NK-2 endogenous ligand, neurokinin A, and is coupled to
      the phospholipase C pathway. Here, we have examined these two binding sites with
      plasmon-waveguide resonance (PWR) spectroscopy that allows the thermodynamics and
      kinetics of ligand-receptor binding processes and the accompanying structural
      changes of the receptor to be monitored, through measurements of the anisotropic
      optical properties of lipid bilayers into which the receptor is incorporated. The
      binding of the three peptides, substance P, neurokinin A, and
      propionyl[Met(O(2))(11)]SP(7-11), to the partially purified NK-1 receptor has
      been analyzed by this method. Substance P and neurokinin A bind to the
      reconstituted receptor in a biphasic manner with two affinities (K(d1) = 0.14 +/-
      0.02 nM and K(d2) = 1.4 +/- 0.18 nM, and K(d1) = 5.5 +/- 0.7 nM and K(d2) = 620
      +/- 117 nM, respectively), whereas only one binding affinity (K(d) = 5.5 +/- 0.4
      nM) could be observed for propionyl[Met(O(2))(11)]SP(7-11). Moreover, binding
      experiments in which one ligand was added after another one has been bound to the
      receptor have shown that the binding of these ligands to each binding site was
      unaffected by the fact that the other site was already occupied. These data
      strongly suggest that these two binding sites are independent and non
      interconvertible on the time scale of these experiments (1-2 h).

PMID- 16618120
TI  - Threonine 41 in beta-catenin serves as a key phosphorylation relay residue in
      beta-catenin degradation.
AB  - Beta-catenin phosphorylation at serine 45 (Ser45), threonine 41 (Thr41), Ser37,
      and Ser33 is critical for beta-catenin degradation, and regulation of beta
      catenin phosphorylation is a central part of the canonical Wnt signaling pathway.
      Beta-catenin mutations at Ser45, Thr41, Ser37, and Ser33 perturb beta-catenin
      degradation and are frequently found in cancers. It is established that Ser45
      phosphorylation by casein kinase I (CKI) initiates phosphorylation at Thr41,
      Ser37, and Ser33 by glycogen synthase kinase 3 (GSK3) and that phosphorylated
      Ser37 and Ser33 are recognized by the F-box protein beta-TrCP, a component of a
      ubiquitin ligase complex that mediates beta-catenin degradation. While the roles
      of Ser45, Ser37, and Ser33 are well documented, the function of Thr41 remains
      less defined. Here we show that Thr41 strictly acts as a phosphorylation relay
      residue and that the Ser-X-X-X-Ser (X is any amino acid) motif is obligatory for
      beta-catenin phosphorylation by GSK3. Beta-catenin phosphorylation/degradation
      and its regulation by Wnt can occur normally in the absence of Thr41 as long as
      the Ser-X-X-X-Ser motif/spacing is preserved. These results suggest that Thr41
      functions to bridge sequential phosphorylation from Ser45 to Ser37 and provide
      further insights into the discrete steps and logic in beta-catenin
      phosphorylation-degradation.

PMID- 16618121
TI  - Pentasaccharide enhances the inactivation of factor Xa by antithrombin by
      promoting the assembly of a Michaelis-type intermediate complex. Demonstration by
      rapid kinetic, surface plasmon resonance, and competitive binding studies.
AB  - It has been demonstrated that a unique pentasaccharide fragment of heparin (H5)
      activates AT by exposing an exosite on the serpin that is a recognition site for
      interaction with the basic autolysis loop (residues 143-154) of fXa. In support
      of this, the substitution of Arg-150 of fXa with Ala (R150A) impaired the
      reactivity of the mutant with AT by 1 order of magnitude specifically in the
      presence H5. To understand the mechanism by which heparin activation of AT
      improves the reactivity of the serpin with fXa, the H5-catalyzed reaction of AT
      with fXa, fXa R150A, and fXa S195A was studied using rapid kinetic, surface
      plasmon resonance, and competitive binding methods. The pseudo-first-order rate
      constants for the H5-catalyzed AT inhibition of both fXa and fXa R150A exhibited
      a linear dependence on the serpin concentration, thereby yielding second-order
      rate constants of 1.0 x 10(6) and 1.5 x 10(5) M(-)(1) s(-)(1), respectively. On
      the other hand, an approximately 70-saccharide, high-affinity heparin-catalyzed
      AT inhibition of both fXa derivatives showed a saturable dependence on the
      inhibitor concentration, yielding an identical rate constant of approximately 20
      s(-)(1), but different ternary fXa-heparin-AT dissociation constants (K(E,ATH))
      of approximately 130 and approximately 1780 nM for wild-type and R150A fXa,
      respectively. Competitive kinetic and surface plasmon resonance binding studies
      using the catalytically inactive S195A mutant of fXa yielded dissociation
      constants of 255 and 610 nM, respectively, for the mutant protease interaction
      with the AT-H5 complex. These results suggest that H5 enhances the reactivity of
      AT with fXa primarily by lowering the K(E,ATH) for the formation of a Michaelis
      type serpin-protease encounter complex.

PMID- 16618122
TI  - Half-of-sites binding of orotidine 5'-phosphate and alpha-D-5-phosphorylribose 1
      diphosphate to orotate phosphoribosyltransferase from Saccharomyces cerevisiae
      supports a novel variant of the Theorell-Chance mechanism with alternating site
      catalysis.
AB  - A ping-pong bi-bi kinetic mechanism ascribed to yeast orotate
      phosphoribosyltransferase (OPRTase) [Victor, J., Greenberg, L. B., and Sloan, D.
      L. (1979) J. Biol. Chem. 254, 2647-2655] has been shown to be inoperative [Witte,
      J. F., Tsou, R., and McClard, R. W. (1999) Arch. Biochem. Biophys. 361, 106-112].
      Radiolabeled orotidine 5'-phosphate (OMP), generated in situ from [7-(14)C]
      orotate and alpha-d-5-phoshorylribose 1-diphosphate (PRPP), binds tightly enough
      to OPRTase (a dimer composed of identical subunits) that the complex survives gel
      filtration chromatography. When a sample of OMP.OPRTase is extensively dialyzed,
      a 1:1 (per OPRTase dimer) complex is detected by (31)P NMR. Titration of the
      apoenzyme with OMP yields a (31)P NMR spectrum with peaks for both free and
      enzyme-bound OMP when OMP is in excess; the complex maintains an OMP/enzyme ratio
      of 1:1 even when OMP is in substantial excess. A red shift in the UV spectrum of
      the OMP.OPRTase complex was exploited to measure K(d(OMP)) = 0.84 muM and to
      verify the 1:1 binding stoichiometry. PRPP forms a Mg(2+)-dependent 1:1 complex
      with the enzyme as observed by (31)P NMR. Isothermal titration calorimetry (ITC)
      experiments revealed 1:1 stoichiometries for both OMP and Mg(2+)-PRPP with
      OPRTase yielding K(d) values of 0.68 and 10 microM, respectively. The binding of
      either 1 equiv of OMP or PRPP is mutually exclusive. ITC experiments demonstrate
      that the binding of OMP is largely driven by increased entropy, suggesting
      substantial distal disordering of the protein. Analytical gel-filtration
      chromatography confirms that the OMP.OPRTase complex involves the dimeric form of
      enzyme. The off rate for release of OMP, determined by magnetization inversion
      transfer, was determined to be 27 s(-)(1). This off rate is somewhat less than
      the k(cat) in the biosynthetic direction (about 39 s(-)(1)); thus, the release of
      OMP from OMP.OPRTase may not be kinetically relevant to the steady-state reaction
      cycle. The body of available data can be explained in terms of alternating site
      catalysis with either a classical Theorell-Chance mechanism or, far more likely,
      a novel "double Theorell-Chance" mechanism unique to alternating site catalysis,
      leading us to propose co-temporal binding of orotate and the release of
      diphosphate as well as the binding of PRPP and the release of OMP that occur via
      ternary complexes in alternating site fashion across the two highly cooperative
      subunits of the enzyme. This novel "double Theorell-Chance" mechanism yields a
      steady-state rate equation indistinguishable in form from the observed classical
      ping-pong bi-bi kinetics.

PMID- 16618123
TI  - Direct biochemical evidence for the utilization of UDP-bacillosamine by PglC, an
      essential glycosyl-1-phosphate transferase in the Campylobacter jejuni N-linked
      glycosylation pathway.
AB  - Campylobacter jejuni has a general N-linked glycosylation pathway, encoded by the
      pgl gene cluster. In C. jejuni, a heptasaccharide is transferred from an
      undecaprenyl pyrophosphate donor [GalNAc-alpha1,4-GalNAc-alpha1,4-(Glcbeta1,3)
      GalNAc-alpha1,4-GalNAc-alpha1,4-GalNAc-alpha1,3-Bac-alpha1-PP-undecaprenyl, where
      Bac is bacillosamine (2,4-diacetamido-2,4,6-trideoxyglucose)] to the asparagine
      side chain of target proteins at the Asn-X-Ser/Thr motif. In this study, we have
      cloned, overexpressed in Escherichia coli, and purified PglC, the glycosyl-1
      phosphate transferase responsible for the first step in the biosynthesis of the
      undecaprenyl-linked heptasaccharide donor. In addition, we report the first
      synthetic route to uridine 5'-diphosphobacillosamine. Using the uridine 5'
      diphosphobacillosamine and undecaprenyl phosphate, we demonstrate the ability of
      PglC to produce undecaprenyl pyrophosphate bacillosamine using radiolabeled HPLC
      and mass spectral analysis. In addition, we revealed that PglC does not accept
      uridine 5'-diphospho-N-acetylglucosamine or uridine 5'-diphospho-N
      acetylgalactosamine as substrates but will accept uridine 5'-diphospho-6
      hydroxybacillosamine, an analogue of bacillosamine that retains the C-6 hydroxyl
      functionality from the biosynthetic precursor. The in vitro characterization of
      PglC as a bacillosamine 1-phosphoryl transferase provides direct evidence for the
      early steps in the C. jejuni N-linked glycosylation pathway, and the coupling of
      PglC with the latter glycosyltransferases (PglA, PglJ, PglH, and PglI) allows for
      the "one-pot" chemoenzymatic synthesis of the undecaprenyl pyrophosphate
      heptasaccharide donor.

PMID- 16618124
TI  - A faster migrating variant masquerades as NICD when performing in vitro gamma
      secretase assays with bacterially expressed Notch substrates.
AB  - Intramembrane proteolysis is a new and rapidly growing field. In vitro assays
      utilizing recombinant substrates for gamma-secretase, an intramembrane-cleaving
      enzyme, are critically important in order to characterize the biochemical
      properties of this unusual enzyme. Several recombinant Notch proteins of varying
      length are commonly used as in vitro substrates for CHAPSO-solubilized gamma
      secretase. Here we report that several recombinant Notch constructs undergo
      limited or no proteolysis in vitro. Instead, upon incubation with or without
      gamma-secretase, variants of the intact protein migrate during SDS-PAGE at the
      location expected for the gamma-secretase specific cleavage products. In
      addition, we show that addition of aspartyl- and gamma-secretase specific
      protease inhibitors are able to retard the formation of these variants
      independent of gamma-secretase, which could lead to the erroneous conclusion that
      Notch cleavage by solubilized gamma-secretase was achieved in vitro even when no
      proteolysis occurred. In contrast, substrates produced in mammalian or insect
      cells are cleaved efficiently in vitro. These observations suggest that in vitro
      studies reliant on recombinant, bacterially produced Notch TMD should be
      performed with the inclusion of additional controls able to differentiate between
      actual cleavage and this potential artifact.

PMID- 16618125
TI  - Structural perturbations induced in linear and circular DNA by the architectural
      protein HU from Bacillus stearothermophilus.
AB  - HU is a small DNA-binding protein of eubacteria that is believed to induce or
      stabilize bending of the double helix and mediate nucleoid compaction in vivo.
      Although HU does not bind preferentially to specific DNA sequences, it is known
      to have high affinity for DNA sites containing structural anomalies, such as
      unpaired or mismatched bases, nicks, and four-way junctions. We have employed
      Raman spectroscopy to further investigate the structural basis of HU-DNA
      recognition in solution. Experiments were carried out on the homodimeric HU
      protein of Bacillus stearothermophilus (HUBst) and a 222-bp DNA fragment, which
      was isolated in linear (DNA(L222)) and circular (DNA(C222)) forms. In the absence
      of bound HUBst the Raman signatures of DNA(L222) and DNA(C222) are nearly
      superimposable, indicating that circularization produces no substantial change in
      the local B-DNA conformation. Conversely, the Raman signatures of DNA(L222) and
      DNA(C222) are perturbed significantly and specifically by HUBst binding. The
      HUBst-induced perturbations are markedly greater for the circularized DNA target.
      These results support an opportunistic molecular mechanism, in which HU binding
      is facilitated by intrinsic nonlinearity or flexibility in the DNA target. We
      propose that DNA segments which are bent or predisposed toward bending provide
      the high-affinity sites for HU attachment and nucleoid condensation. This model
      is consistent with the wide range of DNA bending angles reported in crystal
      structures of HU-DNA complexes.

PMID- 16618126
TI  - Lipid specific activation of the murine P4-ATPase Atp8a1 (ATPase II).
AB  - The asymmetric transbilayer distribution of phosphatidylserine (PS) in the
      mammalian plasma membrane and secretory vesicles is maintained, in part, by an
      ATP-dependent transporter. This aminophospholipid "flippase" selectively
      transports PS to the cytosolic leaflet of the bilayer and is sensitive to
      vanadate, Ca(2+), and modification by sulfhydryl reagents. Although the flippase
      has not been positively identified, a subfamily of P-type ATPases has been
      proposed to function as transporters of amphipaths, including PS and other
      phospholipids. A candidate PS flippase ATP8A1 (ATPase II), originally isolated
      from bovine secretory vesicles, is a member of this subfamily based on sequence
      homology to the founding member of the subfamily, the yeast protein Drs2, which
      has been linked to ribosomal assembly, the formation of Golgi-coated vesicles,
      and the maintenance of PS asymmetry. To determine if ATP8A1 has biochemical
      characteristics consistent with a PS flippase, a murine homologue of this enzyme
      was expressed in insect cells and purified. The purified Atp8a1 is inactive in
      detergent micelles or in micelles containing phosphatidylcholine, phosphatidic
      acid, or phosphatidylinositol, is minimally activated by phosphatidylglycerol or
      phosphatidylethanolamine (PE), and is maximally activated by PS. The selectivity
      for PS is dependent upon multiple elements of the lipid structure. Similar to the
      plasma membrane PS transporter, Atp8a1 is activated only by the naturally
      occurring sn-1,2-glycerol isomer of PS and not the sn-2,3-glycerol stereoisomer.
      Both flippase and Atp8a1 activities are insensitive to the stereochemistry of the
      serine headgroup. Most modifications of the PS headgroup structure decrease
      recognition by the plasma membrane PS flippase. Activation of Atp8a1 is also
      reduced by these modifications; phosphatidylserine-O-methyl ester,
      lysophosphatidylserine, glycerophosphoserine, and phosphoserine, which are not
      transported by the plasma membrane flippase, do not activate Atp8a1. Weakly
      translocated lipids (PE, phosphatidylhydroxypropionate, and
      phosphatidylhomoserine) are also weak Atp8a1 activators. However, N-methyl
      phosphatidylserine, which is transported by the plasma membrane flippase at a
      rate equivalent to PS, is incapable of activating Atp8a1 activity. These results
      indicate that the ATPase activity of the secretory granule Atp8a1 is activated by
      phospholipids binding to a specific site whose properties (PS selectivity,
      dependence upon glycerol but not serine, stereochemistry, and vanadate
      sensitivity) are similar to, but distinct from, the properties of the substrate
      binding site of the plasma membrane flippase.

PMID- 16618127
TI  - Organofluorine inhibitors of amyloid fibrillogenesis.
AB  - The design and application of an effective, new class of organofluorine
      inhibitors of amyloid fibrillogenesis are described. Based on experimental
      evidence a core structure containing indol-3-yl, trifluoromethyl, hydroxyl, and
      carboxylic acid ester functions has been designed. Several substituted
      derivatives of this core structure have been synthesized, using various indole
      derivatives. While all inhibitor candidates have shown considerable effect (20
      70% inhibition) in structure-activity relationship studies (inhibitor/Abeta = 10
      ratio), several compounds have demonstrated excellent activity (93-96%
      inhibition). Using concentration dependence studies, the activity of the most
      active molecules have been quantified. These inhibitors practically completely
      block the fibril formation of Abeta(1)(-)(40), as shown by maximum inhibition
      values (IC(max) = 98-100%). The median inhibitor concentration values (IC(50) =
      0.23-0.53 mol(inhibitor)/mol(A)(beta)) demonstrate favorable stoichiometry for
      the inhibition. The respective elimination of the functional groups from the core
      structure has resulted in a partial or complete loss of activity, indicating the
      significant role of each group. Experiments with these derivatives suggest the
      particular importance of the acidic hydroxyl group during peptide-inhibitor
      interaction.

PMID- 16618128
TI  - Asparagine deamidation: pH-dependent mechanism from density functional theory.
AB  - Asparagine deamidation is a decisive event in chemotherapy-induced apoptosis and
      a major obstacle in the formulation of monoclonal antibodies. Despite the
      importance of deamidation, little is known about the elementary reactions
      involved. B3LYP/6-31+G(d,p)/COSMO-RS calculations were used to obtain stable
      structures and transition states for a network of reactions. Calculated rate
      constants were incorporated into a kinetic model of the pH dependence and
      compared to a pseudo-steady-state model. At low pH, the calculations show that
      deamidation occurs by direct acid-catalyzed hydrolysis to aspartate. At neutral
      to basic pH, deamidation proceeds by the initial formation of a tetrahedral
      intermediate. The intermediate can be converted to succinimide by two pathways
      and three rate-determining steps that shift in relative importance with pH. The
      calculated pH-dependent rate constant qualitatively agrees with the experimental
      pH dependence. The rate-determining transition state structures may help to
      understand chemotherapy-induced apoptosis and improve protein formulations.

PMID- 16618129
TI  - Uniformly sized gold nanoparticles derived from PS-b-P2VP block copolymer
      templates for the controllable synthesis of Si nanowires.
AB  - A monolayer of gold-containing surface micelles has been produced by spin-coating
      solution micelles formed by the self-assembly of the gold-modified polystyrene-b
      poly(2-vinylpyridine) block copolymer in toluene. After oxygen plasma removed the
      block copolymer template, highly ordered and uniformly sized nanoparticles have
      been generated. Unlike other published methods that require reduction treatments
      to form gold nanoparticles in the zero-valent state, these as-synthesized
      nanoparticles are in form of metallic gold. These gold nanoparticles have been
      demonstrated to be an excellent catalyst system for growing small-diameter
      silicon nanowires. The uniformly sized gold nanoparticles have promoted the
      controllable synthesis of silicon nanowires with a narrow diameter distribution.
      Because of the ability to form a monolayer of surface micelles with a high degree
      of order, evenly distributed gold nanoparticles have been produced on a surface.
      As a result, uniformly distributed, high-density silicon nanowires have been
      generated. The process described herein is fully compatible with existing
      semiconductor processing techniques and can be readily integrated into device
      fabrication.

PMID- 16618130
TI  - Large-scale fabrication of periodic nanostructured materials by using hexagonal
      non-close-packed colloidal crystals as templates.
AB  - This letter reports a versatile nonlithographic technique for mass fabricating
      three types of technologically important materials-polymer microwell arrays, 2D
      ordered magnetic nanodots, and semiconductor nanopillar arrays, each with high
      crystalline qualities and wafer-scale sizes. Spin-coated hexagonal non-close
      packed silica colloidal crystals embedded in a polymer matrix are used as
      starting templates to create 2D polymeric microwell arrays. These through-hole
      arrays can then be used as second-generation templates to make periodic magnetic
      nanodots and semiconductor nanopillars. This self-assembly approach is compatible
      with standard semiconductor microfabrication, and complex micropatterns can be
      created for potential device applications. The wafer-scale technique may find
      important applications in biomicroanalysis, high-density magnetic recording
      media, and microphotonics.

PMID- 16618131
TI  - Self-assembly of poly(9,9'-dihexylfluorene) to form highly ordered isoporous
      films via blending.
AB  - Highly ordered hexagonal arrays of isoporous films prepared from poly(9,9'
      dihexylfluorene) and polystyrene-grafted silica nanoparticles (Si-graft-PS) are
      presented. These close-packed arrays were formed in areas of many square
      millimeters. The pore size varied from 3.6 to 8.5 microm, depending on the
      concentration of Si-graft-PS and the processing conditions. Solid-state
      photoluminescence resulted in a significant red shift of up to 30 nm in these
      films compared to that in conventional processing techniques. These differences
      are attributed to enhanced aggregation of the polymers caused by polymer-solvent
      interactions. These highly ordered polymer films may find use in microelectronic
      and biological and/or chemical sensor applications.

PMID- 16618132
TI  - Wettability changes induced by biochemical surface reactions.
AB  - We report the use of proteins, lipids, and enzymes for the preparation of
      surfaces with reversible wettability changes, in particular, surfaces capable of
      switching from hydrophobic to hydrophilic and back. We demonstrate that these
      reactions can be used for engineering capillary systems with gating properties.

PMID- 16618133
TI  - Synthesis and extraction of beta-D-glucose-stabilized Au nanoparticles processed
      into low-defect, wide-area thin films and ordered arrays using CO2-expanded
      liquids.
AB  - This letter presents a straightforward and economic strategy to create aqueous Au
      nanoparticle dispersions using small amounts of beta-D-glucose as a "green"
      alternative to the conventional phase-transfer catalyst approach. Furthermore,
      this new process provides for efficient extraction of these monodisperse Au
      nanoparticles into an organic phase that was successfully processed into wide
      area, locally ordered nanoparticle arrays and thin films using a precisely
      controlled CO2-expanded liquid particle deposition technique. This CO2-based
      technique allows for pressure-tunable particle deposition while eliminating the
      detrimental surface tension and dewetting effects common to normal solvent
      evaporation techniques.

PMID- 16618134
TI  - Effect of confinement on droplet breakup in sheared emulsions.
AB  - The breakup of Newtonian droplets in a Newtonian matrix during shear flow is
      investigated in a counterrotating parallel plate device. For bulk conditions, the
      critical capillary number for breakup is known to be only determined by the
      viscosity ratio. Here, we show that the critical capillary number is also
      affected by the degree of confinement: for low viscosity ratios, confinement
      suppresses breakup, whereas for high viscosity ratios, confinement promotes
      breakup. This way, above a critical value for the degree of confinement, even
      droplets with a viscosity ratio larger than 4, which are unbreakable by shear in
      a bulk situation, can be broken in a simple shear flow field.

PMID- 16618135
TI  - Adhesion of antibody-functionalized polymersomes.
AB  - Polymersomes are vesicles made from synthetic block copolymers. The adhesiveness
      of micron-sized polymersomes, functionalized with antibodies that bind to
      vascular cell adhesion molecules, which could be useful for vascular targeting,
      was measured. Intercellular adhesion molecule-1 (ICAM-1) is an endothelial cell
      adhesion molecule whose expression increases during inflammatory disease, and is
      therefore a natural target for vascular delivery. We functionalized polymersomes
      with an anti-ICAM-1 antibody, using modular biotin-avidin chemistry. Micropipet
      aspiration was used to confirm specific adhesion and measure the adhesion
      strength between an anti-ICAM-1-coated polymersome and an ICAM-1-coated
      polystyrene microsphere at various surface densities of adhesion molecules. The
      adhesion is kinetically trapped, and adhesion strength is quantified by the
      critical tension for detachment. The adhesion strength increases in proportion to
      the surface density of anti-ICAM-1 molecules, in contrast to results seen
      previously when measuring adhesion between biotinylated vesicles and avidin
      coated beads (Lin et al. Langmuir 2004, 20, 5493). The difference in dependence
      on the density of functional groups is likely due to the molecular presentation
      at the vesicle surface; in the current study, the presentation of biotinylated
      anti-ICAM-1 on a layer of avidin leads to the effective presentation of the anti
      ICAM-1 and, thus, a monotonic increase in adhesiveness with antibody density.

PMID- 16618136
TI  - Rheology of viscoelastic mixed surfactant solutions: effect of scission on
      nonlinear flow and rheochaos.
AB  - The linear and nonlinear rheology of viscoelastic mixed anionic-zwitterionic
      surfactant solutions has been systematically investigated. In the linear
      viscoelastic regime, these systems display nearly Maxwellian behavior with a
      unique relaxation time, tau0, and a characteristic elastic plateau modulus, G0.
      Linear rheological data were used to calculate the repitation and breaking times
      of the micelles, tau(rep) and tau(b), respectively. Surprisingly, the elastic
      modulus G0 significantly increases with salt concentration c(s), whereas tau(b)
      decreases by 1 order of magnitude. The strong effect of c(s) on the material
      parameters and microstructure of rodlike micelles allowed for the systematic
      investigation of the effect of these parameters on nonlinear flow. For samples
      with relatively long tau(b), the quasi-static flow diagram (stress vs shear rate)
      shows a stress peak followed by a metastable branch (a region of decreasing shear
      stress), whereas for samples with relatively short tau(b), this phenomenon is not
      observed. Transient flow responses corroborate quasi-static flow findings and
      further reveal the significance of microscopic dynamic parameters on flow
      behavior. Shear stress time series were recorded at constant shear rates, and
      above a critical shear rate, gamma(c2), stress fluctuations are observed. The
      amplitude of these stress fluctuations, Delta sigma, was found to scale as Delta
      sigma approximately equal to G0(tau(b)| gamma - gamma(c2)|)beta with beta
      approximately 0.5. This scaling is observed for micellar systems with tau(b)
      ranging from 0.12 to 0.01 s and G0 ranging from 1 x 10(3) to 7 x 10(3) dyn/cm2.

PMID- 16618137
TI  - Nanotribological properties of alkanephosphonic acid self-assembled monolayers on
      aluminum oxide: effects of fluorination and substrate crystallinity.
AB  - Two phosphonic acid (PA) self-assembled monolayers (SAMs) are studied on three
      aluminum oxide surfaces: the C and R crystallographic planes of single crystal
      alpha-alumina (sapphire) and an amorphous vapor-deposited alumina thin film. SAMs
      are either fully hydrogenated CH3(CH2)17PO3H2 or semifluorinated
      CF3(CF2)7(CH2)11PO3H2. Atomic force microscope (AFM) topographic imaging reveals
      that the deposited films are homogeneous, atomically smooth, and stable for
      months in the laboratory environment. Static and advancing contact angle
      measurements agree with previous work on identical or similar films, but receding
      measurements suggest reduced coverage here. To enable reproducible nanotribology
      measurements with the AFM, a scanning protocol is developed that leads to a
      stable configuration of the silicon tip. Adhesion for the semifluorinated films
      is either comparable to or lower than that for the hydrogenated films, with a
      dependence on contact history observed. Friction between each film and the tips
      depends strongly upon the type of molecule, with the fluorinated species
      exhibiting substantially higher friction. Subtle but reproducible differences in
      friction are observed for a given SAM depending on the substrate, revealing
      differences in packing density for the SAMs on the different substrates. Friction
      is seen to increase linearly with load, a consequence of the tip's penetration
      into the monolayer.

PMID- 16618138
TI  - Orientational anisotropy in the polydomain lamellar phase of a lyotropic liquid
      crystal.
AB  - Diffusion-diffusion correlation measurements by NMR are used to investigate the
      degree of orientational order in the lamellar phase of Aerosol OT (bis(2
      ethylhexyl) sodium sulfosuccinate) and water at a range of surfactant
      concentrations (25, 33, and 50 wt %). We show that true isotropy of the domains
      is found at the lowest concentration but that at higher concentrations deviations
      from isotropy can be found, as evidenced by asymmetry on the 2D correlation
      distributions. We further discuss the significance of asymmetry in diffusion
      diffusion exchange experiments, 2D distributions that should always be symmetric
      in steady state.

PMID- 16618139
TI  - Energetics of small molecule and water complexation in hydrophobic calixarene
      cavities.
AB  - Calixarenes grafted on silica are energetically uniform hosts that bind aromatic
      guests with 1:1 stoichiometry, as shown by binding energies that depend upon the
      calixarene upper rim composition but not on their grafted surface density (0.02
      0.23 nm(-2)). These materials are unique in maintaining a hydrophilic silica
      surface, as probed by H2O physisorption measurements, while possessing a high
      density of hydrophobic binding sites that are orthogonal to the silica surface
      below them. The covalently enforced cone-shaped cavities and complete
      accessibility of these rigidly grafted calixarenes allow the first unambiguous
      measurements of the thermodynamics of guest interaction with the same calixarene
      cavities in aqueous solution and vapor phase. Similar to adsorption into nonpolar
      protein cavities, adsorption into these hydrophobic cavities from aqueous
      solution is enthalpy-driven, which is in contrast to entropy-driven adsorption
      into water-soluble hydrophobic hosts such as beta cyclodextrin. The adsorption
      thermodynamics of several substituted aromatics from vapor and liquid are
      compared by (i) describing guest chemical potentials relative to pure guest,
      which removes differences among guests because of aqueous solvation and van der
      Waals contacts in the pure condensed phase, and (ii) passivating residual guest
      binding sites on exposed silica, titrated by water during adsorption from aqueous
      solution, using inorganic salts before vapor adsorption. Adsorption isotherms
      depend only upon the saturation vapor pressure of each guest, indicating that
      guest binding from aqueous or vapor media is controlled by van der Waals contacts
      with hydrophobic calixarene cavities acting as covalently assembled condensation
      nuclei, without apparent contributions from CH-pi or other directional
      interactions. These data also provide the first direct quantification of free
      energies for interactions of water with the calixarene cavity interior. The
      calixarene-water interface is stabilized by approximately 20 kJ/mol relative to
      the water-vapor interface, indicating that water significantly competes with the
      aromatic guests for adsorption at these ostensibly hydrophobic cavities. This
      result is useful for understanding models of water interactions with other
      concave hydrophobic surfaces, including those commonly observed within proteins.

PMID- 16618140
TI  - Rheometry-PIV of shear-thickening wormlike micelles.
AB  - The shear-thickening behavior of an equimolar semidilute aqueous solution of 40
      mM/L cetylpyridinium chloride and sodium salicylate was studied in this work by
      using a combined method of rheometry and particle image velocimetry (PIV).
      Experiments were conducted at 27.5 degrees C with Couette, vane-bob, and
      capillary rheometers in order to explore a wide shear stress range as well as the
      effect of boundary conditions and time of flow on the creation and destruction of
      shear-induced structures (SIS). The use of the combined method of capillary
      rheometry with PIV allowed the detection of fast spatial and temporal variations
      in the flow kinematics, which are related to the shear-thickening behavior and
      the dynamics of the SIS but are not distinguished by pure rheometrical
      measurements. A rich-in-details flow curve was found for this solution, which
      includes five different regimes. Namely, at very low shear rates a Newtonian
      behavior was found, followed by a shear thinning one in the second regime. In the
      third, shear banding was observed, which served as a precursor of the SIS and
      shear-thickening. The fourth and fifth regimes in the flow curve were separated
      by a spurtlike behavior, and they clearly evidenced the existence of shear
      thickening accompanied by stick-slip oscillations at the wall of the rheometer,
      which subsequently produced variations in the shear rate under shear stress
      controlled flow. Such a stick-slip phenomenon prevailed up to the highest shear
      stresses used in this work and was reflected in asymmetric velocity profiles with
      spatial and temporal variations linked to the dynamics of creation and breakage
      of the SIS. The presence of apparent slip at the wall of the rheometer provides
      an energy release mechanism which leads to breakage of the SIS, followed by their
      further reformation during the stick part of the cycles. In addition, PIV
      measurements allowed the detection of apparent slip at the wall, as well as
      mechanical failures in the bulk of the fluid, which suggests an extra
      contribution of the shear stress field to the SIS dynamics. Increasing the
      residence time of the fluid in the flow system enhanced the shear-thickening
      behavior. Finally, the flow kinematics is described in detail and the true flow
      curve is obtained, which only partially fits into the scheme of existing
      theoretical models for shear-thickening solutions.

PMID- 16618141
TI  - Electrochemical, microscopic, and spectroscopic characterization of prevesicle
      nanostructures and vesicles on mixed cationic surfactant systems.
AB  - Several experimental techniques (conductivity, zeta potential, transmission
      electronic microscopy, and steady-state fluorescence spectroscopy) have been used
      to study the formation of mixed colloidal aggregates consisting of a cationic
      double-chain surfactant, di-dodecyldimethylammonium bromide (di-C12DMAB), and a
      single-chain alkyltrimethylammonium bromide with 10 and/or 14 carbon atoms
      (decyltrimethylammonium bromide, C10TAB, and/or tetradecyltrimethylammonium
      bromide, C14TAB). Special interest has been devoted to the prevesicle domain,
      within which the formation of aggregated nanostructures was first reported in our
      laboratory. For that purpose, studies have been carried out on the very dilute
      region by means of conductivity experiments, confirming the existence of two
      critical aggregation concentrations in that concentration domain: the so-called
      mixed critical aggregate concentration, CAC, and the mixed critical vesicle
      concentration, CVC. By carrying out TEM experiments on negatively stained
      samples, we were surprised to find a number of aggregates without a clear
      aggregation pattern and with a variety of sizes and shapes at concentrations
      below CAC, where only monomers were expected. However, the nanoaggregates found
      at concentrations between CAC and CVC, also by TEM microscopy, show a clear and
      ordered "fingerprint"-like aggregation pattern similar to the liquid-crystalline
      phases reported for DNA-liposome complexes and/or DNA packed with viral capsids.
      Finally, at total surfactant concentrations above CVC, the aggregates were
      confirmed, by means of cryo-TEM micrographs and zeta potential measurements, to
      be essentially unilamellar spherical vesicles with a medium polydispersity and a
      net-averaged surface density charge of around 12 x 10(-3) C m(-2). The
      fluorescence emission of two probes, TNS (anionic) and PRODAN (nonionic), allows
      for the analysis of the micropolarity and microviscosity of the different
      microenvironments present in aqueous surfactant solutions where the above
      mentioned vesicle and prevesicle aggregates are present.

PMID- 16618142
TI  - Synthesis of anisotropic nanoparticles by seeded emulsion polymerization.
AB  - Anisotropic polystyrene nanoparticles of diameters below 0.5 microm were prepared
      by coating the surface of cross-linked polystyrene latex particles with a thin
      hydrophilic polymer layer prior to swelling the particles with styrene and then
      initiating second-stage free-radical polymerization. Conditions were found so
      that all particles had uniform asymmetry. The effect of surface chemistry on the
      development of particle anisotropy during seeded emulsion polymerization of sub
      0.5 microm diameter particles was studied. The extent and uniformity of the
      anisotropy of the final particles depended strongly on the presence of the
      hydrophilic surface coating. Systematic variation of the degree of hydrophilicity
      of the surface coating provided qualitative insight into the mechanism
      responsible for anisotropy. Conditions were chosen so that the surface free
      energy favored the extrusion of a hydrophobic bulge of monomer on the hydrophilic
      surface of the particle during the swelling phase: the presence of a hydrophilic
      layer on the particle surface causes this asymmetry to be favored above uniform
      wetting of the particle surface by the monomer. Kinetic effects, arising from the
      finite time required for the seed to swell with the monomer, also play a role.

PMID- 16618143
TI  - New amphiphilic diblock copolymers: surfactant properties and solubilization in
      their micelles.
AB  - Several series of amphiphilic diblock copolymers are investigated as
      macrosurfactants in comparison to reference low-molar-mass and polymeric
      surfactants. The various copolymers share poly(butyl acrylate) as a common
      hydrophobic block but are distinguished by six different hydrophilic blocks (one
      anionic, one cationic, and four nonionic hydrophilic blocks) with various
      compositions. Dynamic light scattering experiments indicate the presence of
      micelles over the whole concentration range from 10(-4) to 10 g x L(-1).
      Accordingly, the critical micellization concentrations are very low. Still, the
      surface tension of aqueous solutions of block copolymers decreases slowly but
      continuously with increasing concentration, without exhibiting a plateau. The
      longer the hydrophobic block, the shorter the hydrophilic block, and the less
      hydrophilic the monomer of the hydrophilic block is, the lower the surface
      tension is. However, the effects are small, and the copolymers reduce the surface
      tension much less than standard low-molar-mass surfactants. Also, the copolymers
      foam much less and even act as anti-foaming agents in classical foaming systems
      composed of standard surfactants. The copolymers stabilize O/W emulsions made of
      methyl palmitate as equally well as standard surfactants but are less efficient
      for O/W emulsions made of tributyrine. However, the copolymer micelles exhibit a
      high solubilization power for hydrophobic dyes, probably at their core-corona
      interface, in dependence on the initial geometry of the micelles and the
      composition of the block copolymers. Whereas micelles of copolymers with strongly
      hydrophilic blocks are stable upon solubilization, solubilization-induced
      micellar growth is observed for copolymers with moderately hydrophilic blocks.

PMID- 16618144
TI  - One-step preparation of chitosan-coated cationic liposomes by an improved
      supercritical reverse-phase evaporation method.
AB  - High-pressure carbon dioxide in contact with water dissolves to form carbonic
      acid, causing a decrease in pH. By use of these characteristics of a CO2/H2O
      biphasic system, chitosan-coated cationic liposomes of l-alpha
      dipalmitoylphosphatidylcholine were successfully prepared by an improved
      supercritical reverse-phase evaporation (ISCRPE) method. Liposome-chitosan
      complexes carrying a positive charge were prepared in a single-step procedure
      without the use of acid or organic solvent, including ethanol. The maximum
      trapping efficiency of liposomes prepared by the ISCRPE method was 17%, with or
      without the addition of chitosan, compared to only 2% for liposomes prepared by
      the Bangham method. Furthermore, the liposomal dispersion was stable at room
      temperature in a sealed tube for over 30 days.

PMID- 16618145
TI  - The stability of L3 sponge phase in acidic solutions.
AB  - In the synthesis of the disordered lyotropic liquid crystalline L3 sponge phase
      prepared with the cosurfactants cetylpyridinium chloride and hexanol, aqueous
      NaCl solution is used as the solvent. When this sponge phase is used as the
      template for L3 silica-phase processing, we replace NaCl with HCl to facilitate
      the acid catalysis of tetramethoxysilane in forming a templated silica gel,
      assuming that changing the solvent from NaCl(aq) to HCl(aq) of equivalent ionic
      strength does not affect the stability range of the L3 phase. In this work, we
      confirm that changing the pH of the solvent from neutral to acidic (with HCl) has
      negligible effect on the L3 phase region. Equivalent ionic strength is provided
      by either NaCl(aq) or HCl(aq) solvent; therefore, a similar phase behavior is
      observed regardless of which aqueous solvent is used.

PMID- 16618146
TI  - Osmotic compression and expansion of highly ordered clay dispersions.
AB  - Aqueous dispersions of nanometric clay platelets (Laponite) have been dewatered
      through different techniques: centrifugation, mechanical compression, and osmotic
      stress (dialysis against a polymer solution). The positional and orientational
      correlations of the particles have been determined through small-angle neutron
      scattering. Uniaxial compression experiments produce concentrated dispersions
      (volume fraction > 0.03) in which the platelets have strong orientational and
      positional correlations. The orientational correlations cause the platelets to
      align with their normal along a common axis, which is the axis of compression.
      The positional correlations cause the platelets to be regularly spaced along this
      direction, with a spacing that matches the average volume per particle in the
      dispersion. The swelling law (volume fraction versus separation distance) is one
      dimensional, as in a layered system. Changes in the applied osmotic pressure
      cause the water content of the dispersion to either rise or decrease, with time
      scales that are controlled by interparticle friction forces and by hydrodynamic
      drag. At long times, the dispersions approach osmotic equilibrium, which can be
      defined as the common limit of swelling and deswelling processes. The variation
      of the equilibrium water content with the applied osmotic pressure has been
      determined over 1 decade in volume fractions (0.03 < phi < 0.3) and 3 decades in
      pressures. This equation of state matches the predictions made from the knowledge
      of the forces and thermal agitation for all components in the dispersion
      (particles, ions, and water).

PMID- 16618147
TI  - Monte carlo simulations of micellization in model ionic surfactants: application
      to sodium dodecyl sulfate.
AB  - A lattice model for ionic surfactants with explicit counterions is proposed for
      which the micellization behavior can be accurately determined from grand
      canonical Monte Carlo simulations. The model is characterized by a few parameters
      that can be adjusted to represent various linear surfactants with ionic
      headgroups. The model parameters have a clear physical interpretation and can be
      obtained from experimental data unrelated to micellization, namely, geometric
      information and solubilities of tail segments. As a specific example, parameter
      values for sodium dodecyl sulfate were obtained by optimizing for the solubility
      of hydrocarbons in water and the structural properties of dodecane. The critical
      micelle concentration (cmc), average aggregation number, degree of counterion
      binding, and their dependence on temperature were determined from histogram
      reweighting grand canonical Monte Carlo simulations and were compared to
      experimental results. The model gives the correct trend and order of magnitude
      for all quantities but underpredicts the cmc and aggregation number. We suggest
      ways to modify the model that may improve agreement with experimental values.

PMID- 16618148
TI  - Differences between tethered polyelectrolyte chains on bare mica and
      hydrophobically modified mica.
AB  - This study investigates the structures of layers of amphiphilic diblock
      copolymers of poly(t-butyl styrene)-poly(styrene sulfonate) (PtBS-PSS) adsorbed
      on both the bare mica surface (hydrophilic) and an octadecyltriethoxysilane (OTE)
      modified mica surface (hydrophobic). When the surface is rendered hydrophobic,
      the nonsoluble block exhibits stronger interaction with the surface and higher
      adsorbed masses are achieved. Interaction forces between two such adsorbed layers
      on both substrates were measured using the surface forces apparatus. The effect
      of salt concentration (Cs) and molecular weight (N) on the height of the self
      assembled layers (L0) was examined in each case. The resulting scaling
      relationship is in good agreement with predictions of the brush model, L0
      proportional to N(1.0) in the low-salt limit and L0N(-1) proportional to
      (Cs/sigma)(-0.32) in the salted regime, when adsorption takes place onto the
      hydrophobized mica surface. For adsorption on the bare mica surface, L0N(-0.7)
      proportional, variant Cs(-0.17) agrees with the scaling prediction of the sparse
      tethering model. The results suggest that, on the hydrophilic bare mica surface,
      the adsorbed amount is not high enough to form a brush structure and only very
      little intermolecular stretching of the tethered chains occurs; in contrast, the
      presence of the hydrophobic OTE layer increases the tethering density such that
      the polyelectrolyte chains adopt a brush conformation.

PMID- 16618149
TI  - Covalent molecular assembly in supercritical carbon dioxide: a comparative study
      between amine- and anhydride-derivatized surfaces.
AB  - Layer-by-layer covalent assembly of an oligoimide on an anhydride- derivatized
      silicon dioxide surface is investigated using supercritical carbon dioxide
      (SCCO2) as the depositing medium. The deposited films were characterized by X-ray
      photoelectron spectroscopy (XPS), ellipsometry (VASE), UV-visible spectroscopy,
      electrochemical impedance spectroscopy, nano indentation, and atomic force
      microscopy (AFM) and the properties of the films compared with those of an
      oligoimide deposited on amine-derivatized surfaces. Films formed on the anhydride
      surface are more uniform and stable possibly because the silane precursor for the
      anhydride is anchored to the surface through two (-Si-O-Si-) tripods. XPS results
      indicate that the interfacial reaction resulting in amide formation is almost
      complete in the case of the anhydride, but not in the case of the amine. We infer
      that the twin tripods linking the anhydride group to the surface may have
      improved the accessibility of the functional groups for immobilization of the
      next layer, thereby contributing to the better quality.

PMID- 16618150
TI  - Growth of gold nanoparticle films driven by the coalescence of particle
      stabilized emulsion drops.
AB  - We have investigated the mechanism of the spontaneous growth of a gold
      nanoparticle film on a container wall when an aqueous dispersion of gold
      nanoparticles is shaken with an oil phase containing octadecylamine, as first
      described by Mayya and Sastry (Mayya, K. S.; Sastry, M. Langmuir 1999, 15,
      1902.). Experimental evidence is described, which shows that the film growth is
      driven by the coalescence of particle-coated emulsion drops with the flat oil
      water interface separating the oil and water phases.

PMID- 16618151
TI  - Water-vapor plasma-based surface activation for trichlorosilane modification of
      PMMA.
AB  - Separation rates and resolutions within capillary electrophoretic (CE) systems
      can be enhanced when surface zeta potentials are uniform with minimum deviations
      from ideal pluglike flow. Microfluidic CE devices based on poly(methyl
      methacrylate) (PMMA) are being developed due to the optical clarity,
      availability, stability, and reproducible electroosmotic flow (EOF) rates
      displayed by this polymer. Control of EOF in polymer-based CE systems can be
      achieved by surface zeta potential alteration through chemical modification.
      Herein, a method will be presented for the surface functionalization of PMMA with
      chemistry analogous to formation of trichlorosilane self-assembled monolayers on
      SiO2. The current method involves two separate steps. First, surface activation
      with water-vapor plasma introduces surface hydroxylation. Second, treatment of
      the plasma-treated PMMA with a substituted trichlorosilane solution forms the
      functional surface layer. The modified surfaces were characterized using several
      analytical techniques, including water contact angle, X-ray photoelectron
      spectroscopy, Fourier transform infrared-attenuated total reflection, secondary
      ion mass spectroscopy, and measurement of EOF velocities within PMMA
      microchannels.

PMID- 16618152
TI  - Regulation of supramolecular chirality and morphology of the LB film of achiral
      barbituric acid by amphiphilic matrix molecules.
AB  - Previously, we have found that an achiral barbituric acid (BA) derivative, 5-(4
      (N-methyl-N-hexadecylaminobenzylidene))-2,4,6-(1H,3H)-pyrimidinetrione (BAC16),
      could form molecular assemblies showing supramolecular chirality through the
      organization at the air/water interface. To acquire more knowledge of the
      formation mechanism of such supramolecular assemblies, some achiral molecules,
      such as stearic acid (SA), octadecylamine (ODA), and an analogue of BA without an
      alkyl chain, were mixed into the BAC16 system. The effects of these matrix
      molecules on the supramolecular chirality and surface morphologies of Lanmuir
      Blodgett (LB) films were investigated. It was observed that, at a low molar ratio
      of the matrix molecules (below 10%), the chirality of the BAC16 assemblies could
      be maintained with only a reduction in the intensity. When the matrix fraction
      was increased, the supramolecular chirality of the mixed films disappeared. The
      addition of the matrix molecules can greatly change the surface morphologies of
      the mixed films. When SA was mixed with BAC16, the spiral nanofibers of BAC16
      were changed to long nanofibers. When ODA was mixed, the hydrolytic cleavage
      reaction of BAC16 took place at the air/water interface and disordered spirals
      were obtained. When the analogous BA derivate without an alkyl chain was mixed,
      the phase-separating morphology was observed. These changes in the chirality and
      surface morphologies indicated firmly that the supramolecular chirality of BAC16
      films were formed due to the cooperative arrangement of the molecules. A certain
      amount of matrix molecules will destroy the cooperative arrangement and thus the
      chirality.

PMID- 16618153
TI  - Self-assembly of 1,4-benzenedithiolate/tetrahydrofuran on a gold surface: a Monte
      Carlo simulation study.
AB  - We report a Monte Carlo simulation study of the self-assembly of 1,4
      benzenedithiolate (BDT), tetrahydrofuran (THF), and their mixtures on a Au (111)
      surface. We use the grand canonical Monte Carlo method to obtain the equilibrium
      adsorption coverage. Canonical ensemble (NVT) simulation is then used to explore
      further the structural information of the equilibrated systems. Our results
      indicate that BDT molecules adsorb onto the Au (111) surface with one of the
      sulfur atoms bonded to Au atoms. THF molecules form clusters on the surface. For
      BDT-THF mixtures, BDT can selectively adsorb on Au (111) to form a monolayer,
      whereas the solvent THF molecules either float above BDT monolayer or occupy
      vacancies on the surface that are not covered by BDT molecules. BDT molecules
      adsorb on a Au (111) surface with an average tilt angle of about 18-35 degrees to
      the surface normal. The tilting angle decreases as the coverage increases. In
      addition, the BDT monolayer constitutes an ordered herringbone structure on the
      Au (111) surface, and the ordering pattern is insensitive to the BDT coverage. In
      comparison, the THF molecules exhibit amorphous structure on the Au surface.
      Interestingly, simulations indicate that the bonding behavior of BDT molecules on
      Au (111) is coverage-dependent. BDT bonds preferably on the Au top site when the
      surface coverage is low. As coverage increases, most BDT molecules bond on the
      bridge and fcc hollow sites.

PMID- 16618154
TI  - Characterization of metal-supported poly(methyl methacrylate) microstructures by
      FTIR imaging spectroscopy.
AB  - Thin microstructured poly(methyl methacrylate) (PMMA) films may be used as
      scaffolds for biosensor arrays. Microstructured pores form miniaturized vessels,
      each constituting an individual reaction vessel or detector element. Arrays of
      micropores with diameters between 2 and 80 microm were prepared in thin PMMA
      films on gold by optical lithography. Laterally resolved chemical information for
      microstructured PMMA films on a gold substrate was obtained by FTIR spectroscopic
      imaging. The carbonyl band was used to characterize the microstructure.
      Spectroscopic results indicate small amounts of PMMA residues inside the pores. A
      downshift of 5 cm(-1) compared to the position of the PMMA bulk carbonyl band
      indicates interactions of the PMMA residue with the gold substrate. Additional
      small bands are observed which indicate the formation of carboxylate during PMMA
      microstructuring. Three possible types of strong PMMA-gold interactions are
      discussed. All strong PMMA-gold interactions involve carbonyl or carboxyl oxygen.

PMID- 16618155
TI  - Self-assembly of a diblock copolymer on a patterned surface with low-energy
      electron beam.
AB  - A pattern was generated by 500 eV electron beam irradiation on benzaldimine
      monolayer through a grid and subsequent hydrolysis of nonirradiated regions.
      While we tried to assemble a block copolymer, polystyrene-block-poly(4
      vinylpyridine) (PS-b-P4VP), on the pattern, we observed that the polarity
      difference between the two different regions was not right for discriminating the
      wetting behavior of two blocks of the polymer. Among various modifications of the
      retrieved amine, it was found that tribromoacetaldehyde was suitable for this
      end. Surprisingly, treatment of the aldehyde gave a surface preferring the
      polystyrene block to poly(4-vinylpyridine) block, while the irradiated section
      favored the latter block. As a result, island morphology was observed on the
      tribromoacetaldimine region and hole morphology on the irradiated region when the
      film thickness was 1.3Lo. Contact angle data were consistent with the observed
      symmetric wetting on the former region and the asymmetric one on the latter.

PMID- 16618156
TI  - Fluorination of the hydrophilic head accelerates the collapse of the monolayer
      but stabilizes the bilayer of a long-chain trifluoroethyl ether on water.
AB  - A comparison of the collapse of Langmuir monolayers of docosyl trifluoroethyl
      ether (DFEE) and docosyl ethyl ether (DEE) on water shows that in both films the
      3D phase is formed layer-by-layer. The substitution of CH3 by a CF3 group in the
      hydrophilic head yields a more stable bilayer exhibiting lower equilibrium
      spreading pressure, pi(esp)(DFEE) < pi(esp)(DEE). Upon lateral compression, the
      DFEE bilayer fractures abruptly as a compact solid body whereas the DEE bilayer
      breaks down gradually as a polycrystalline material. A comparison of the collapse
      kinetics of the two films at the same constant supersaturation pi-pi(esp) = 7
      mN/m shows that the fluorinated DFEE monolayer transforms more quickly, yielding
      a stable bilayer of closely packed upright molecules, whereas the DEE film
      undergoes a continuous monolayer-bilayer-multilayer transition. Brewster angle
      microscopy allows us to visualize different collapse mechanisms of the DFEE and
      DEE films; the domains of the fluorinated DFEE bilayer grow laterally at constant
      thickness and density, and the collapse of the nonfluorinated DEE monolayer
      occurs through a sequence of disordered stripelike and broken elongated textures.
      The characteristic molecular areas of the monolayer and bilayer collapse suggest
      that the 2D-3D transition in the DFEE and DEE films is accompanied by at least
      partial dehydration of their headgroups. The faster collapse of the fluorinated
      monolayer could result from a lower energy barrier due to the more hydrophobic
      CF3 group in the heads. The increased stability of the DFEE bilayer could be
      associated with the electrostatic attraction between the -C(F delta-)3 versus (H
      delta+)3C- terminals at the heads-to-tails contact plane of the top and the
      bottom layer, contrasting with the repulsion between the -C(H delta+)3 versus (H
      delta+)3C- terminals of the top-layer heads and the bottom-layer tails in the DEE
      bilayer.

PMID- 16618157
TI  - Lattice Boltzmann simulations of droplet formation in a T-shaped microchannel.
AB  - We investigated the formation of a droplet from a single pore in a glass chip,
      which is a model system for droplet formation in membrane emulsification. Droplet
      formation was simulated with the lattice Boltzmann method, a method suitable for
      modeling on the mesoscale. We validated the lattice Boltzmann code with several
      benchmarks such as the flow profile in a rectangular channel, droplet deformation
      between two shearing plates, and a sessile drop on a plate with different wetting
      conditions. In all cases, the modeling results were in good agreement with the
      benchmark. A comparison of experimental droplet formation in a microchannel glass
      chip showed good quantitative agreement with the modeling results. With this
      code, droplet formation simulations with various interfacial tensions and various
      flow rates were performed. All resulting droplet sizes could be correlated
      quantitatively with the capillary number and the fluxes in the system.

PMID- 16618158
TI  - Surface interactions during polyelectrolyte multilayer build-up. 2. The effect of
      ionic strength on the structure of preformed multilayers.
AB  - Interactions between surfaces bearing multilayer films of poly(allylamine
      hydrochloride) (PAH) and poly(styrenesulfonate sodium salt) (PSS) were
      investigated across a range of aqueous KBr solutions. Three layer films
      (PAH/PSS/PAH) were preassembled on mica surfaces, and the resulting interactions
      were measured with the interferometric surface force apparatus (SFA). Increasing
      the ionic strength of the medium resulted in a progressive swelling of the
      multilayer films. Interactions in solutions containing more than 10(-3) M KBr
      were dominated by a long-ranged steric repulsion originating from compression of
      polyelectrolyte segments extending into solution. In 10(-1) M KBr, repeated
      measurements at the same contact position showed a considerable reduction of the
      range and the strength of the steric force, indicating a flattening of the film
      during initial approach. Furthermore, this flattening was irreversible on the
      time scale of the experiments, and measurements performed up to 72 h after the
      initial compression showed no signs of relaxation. These studies aid in
      understanding the dominant interactions between polyelectrolyte multilayers,
      including polyelectrolyte films deposited on colloidal particles, which is
      important for the preparation of colloidally stable nanoengineered particles.

PMID- 16618159
TI  - Reductive hydrodechlorination of trichloroethylene by palladium-on-alumina
      catalyst: 13C solid-state NMR study of surface reaction precursors.
AB  - Adsorption of trichloroethylene (TCE) on alumina-supported palladium catalysts
      (Pd/Al2O3) was studied in the presence and absence of hydrogen using 13C-solid
      state NMR. Carbon-13 NMR spectra indicate that at low coverage strongly adsorbed
      species are formed while at high coverage additional physisorbed species are
      present. Carbon-13 spin-echo amplitude data measured as a function of pulse
      separation, tau, was used to determine the 13C-13C intramolecular dipolar
      coupling and the carbon-carbon bond length of adsorbed species. Results indicate
      that a substantial fraction of the chemisorbed carbon species had undergone
      carbon-carbon bond scission forming single-carbon fragments, suggesting that the
      activation energy for carbon-carbon bond scission is comparable to the heat of
      adsorption. For the remaining surface species, the double bond is elongated to
      1.46 +/- 0.03 A and is suspected to be chemically bonded ethynyl. At room
      temperature, adding an excess of hydrogen to catalyst that is covered to
      saturation with TCE precursors produces only in a small amount of ethane,
      indicating the fraction of surface species that are hydrodehalogenation
      precursors is small.

PMID- 16618160
TI  - Accurate relations between pore size and the pressure of capillary condensation
      and the evaporation of nitrogen in cylindrical pores.
AB  - To examine the theoretical and semiempirical relations between pore size and the
      pressure of capillary condensation or evaporation proposed so far, we constructed
      an accurate relation between the pore radius and the capillary condensation and
      evaporation pressure of nitrogen at 77 K for the cylindrical pores of the ordered
      mesoporous MCM-41 and SBA-15 silicas. Here, the pore size was determined from a
      comparison between the experimental and calculated X-ray diffraction patterns due
      to X-ray structural modeling recently developed. Among the many theoretical
      relations that differ from each other in the degree of theoretical improvements,
      a macroscopic thermodynamic approach based on Broekhoff-de Boer equations was
      found to be in fair agreement with the experimental relation obtained in the
      present study.

PMID- 16618161
TI  - Spectroscopic characterization of omega-substituted biphenylthiolates on gold and
      their use as substrates for "on-top" siloxane SAM formation.
AB  - Self-assembled monolayers (SAMs) of omega-substituted biphenylthiolates (omega
      MBP) on gold were characterized by spectral ellipsometry, X-ray photoelectron
      spectroscopy (XPS), infrared reflection absorption spectroscopy (IRRAS), and
      vibrational sum frequency generation spectroscopy (VSFG). The vibrational studies
      of the SAMs were supported by an ab initio frequency analysis at HF/6-31G and
      BP86/6-31G levels, yielding an assignment of all relevant spectral features in
      the range from 3500 to 1200 cm(-1). We were able to demonstrate that hydroxy
      terminated MBP (HMBP) SAMs are basically featureless in the range of the CH
      stretching vibrations. Accordingly, the adsorption of a SAM of
      octadecyltrichlorosilane (OTS) on top of this model surface could be studied. A
      red shift of the C-O stretching vibration from 1281 to 1264 cm(-1) was observed
      during the chemisorption of OTS, thus allowing for a quantification of the number
      of OTS molecules involved in surface binding of OTS, which was found to be about
      26% on average.

PMID- 16618162
TI  - Influence of the solvent environment on the contact mechanics of tip-sample
      interactions in friction force microscopy of poly(ethylene terephthalate) films.
AB  - Friction force microscopy measurements have been carried out on free-standing
      films of poly(ethylene terephthalate) in a variety of different media. In
      ethanol, the adhesion force was small, and the friction-load relationship was
      linear. In perfluorodecalin, nonlinearity was observed in the friction-load
      relationship, and the data have been found to fit the Johnson-Kendall-Roberts
      model of contact mechanics. The behavior in hexadecane was also characterized by
      a single-asperity contact model, but in this case, the data were found to fit the
      Derjaguin-Muller-Toporov model. It is suggested that these differences are due to
      the different strengths of tip-sample adhesion, which arise from the differences
      in the dielectric constants of the media: in ethanol, which has a high dielectric
      constant, the friction force varies linearly with the load, whereas in media of
      low dielectric constant, adhesion-limited behavior is observed.

PMID- 16618163
TI  - Order and composition of methyl-carboxyl and methyl-hydroxyl surface-chemical
      gradients.
AB  - A detailed infrared and XPS characterization of surface-chemical gradients of
      dodecanethiol with 11-mercaptoundecanol or 11-mercaptoundecanoic acid self
      assembled on gold, is reported. Gradients were prepared using a simple, two-step
      process previously reported from our laboratory, which involves a controlled
      immersion of a polycrystalline gold substrate in a dilute (5 microM) solution of
      one component and a subsequent back-filling with the other. FTIR measurements
      show that a single-component gradient of dodecanethiol is composed of disordered,
      liquidlike alkyl chain conformations. Such a gradient, when back-filled with a
      complementary thiol, having either a hydroxyl or carboxyl end-group, yields two
      component gradients that show similar changes in wettability along their lengths.
      However, while gradients composed of methyl and hydroxyl end-groups show a well
      ordered alkyl chain structure over their entire length, methyl-carboxyl gradients
      exhibit a greater conformational disordering toward the carboxyl-rich end.

PMID- 16618164
TI  - Microdroplet dissolution into a second-phase solvent using a micropipet
      technique: test of the Epstein-Plesset model for an aniline-water system.
AB  - The Epstein-Plesset model was originally derived for the dissolution of a single
      gas bubble in an infinite aqueous solution (Epstein, P. S.; Plesset, M. S. J.
      Chem. Phys. 1950, 18, 1505-1509). The micropipet manipulation technique was
      previously shown to test this theory on air microbubbles and air-filled lipid
      coated microparticles accurately and appropriately (Duncan, P. B.; Needham, D.
      Langmuir 2004, 20, 2567-2578). This same theory is now tested to model liquid
      microdroplet dissolution in a well-defined solution environment. As presented
      previously for the gas-bubble system, holding a single microparticle at the end
      of a micropipet was not shown to affect the dissolution profile and allowed
      isotropic diffusion significantly, a necessary condition for the validation of
      the theory. Here, an aniline-water system with an initial droplet diameter of 50
      microm was used as a model liquid-liquid system. A microdroplet of aniline in an
      aqueous solution presatureated with aniline at distinct levels was tested, as was
      the reverse system of a water droplet in an aniline solution. The dissolution
      lifetime was shown to increase with increasing medium saturation fraction
      according to the Epstein-Plesset time-dependent theory (including the time
      required to establish the stationary layer) neglecting interfacial tension. The
      droplet lifetime can be increased by an order of magnitude (from about 10 to 100
      s) by increasing the saturation fraction from 0 to 0.9 and by another order of
      magnitude by increasing from 0.9 to 0.99. The technique proved to be an accurate
      and appropriate method to test the dissolution of single liquid microdroplets in
      a second liquid solution and establishes a systematic experimental and
      theoretical approach to the investigation of the formation of polymer and other
      microparticles.

PMID- 16618165
TI  - Controlled, simultaneous assembly of polyethylenimine onto nanoparticle silica
      colloids.
AB  - A novel precision-assembly methodology is described on the basis of the
      controlled, simultaneous assembly (CSA) of a core nanoparticle substrate and
      polyelectrolyte solutions. The method is capable of assembly rates at least as
      fast as 10(16) core particles s(-1) L(-1) and affords concentrated suspensions of
      stable colloids with an adsorbed polyelectrolyte. The resulting dispersions are
      highly homogeneous, have a low viscosity and narrow particle-size distribution,
      and are stable colloids, even at solid concentrations of at least 33 wt %. The
      adsorption isotherm and the saturation adsorption for polyethylenimine (PEI)
      assemblies onto a 15 nm silica colloid have been evaluated with 1H NMR
      spectroscopy. The saturation adsorption is highly dependent upon the pH at
      assembly and is given by the equation PEIa (micromol m(-2)) = 1.73pH - 1.89, R2 =
      0.986, where micromoles refers to the concentration of the EI monomer. The
      saturation concentration increases from 6.8 micromol m(-2) at pH 5.0 to 13.7
      micromol m(-2) at pH 9.0. The adsorbed polyelectrolyte may be cross-linked and
      thereby permanently fixed to the colloid surface to prepare nanoparticle
      polyelectrolyte colloidal assemblies having enhanced colloid stability, high
      homogeneity, and a high fraction (>80%) of permanently adsorbed polyelectrolyte.
      These assemblies are stable at physiological pH and ionic strength and may
      represent ideal substrates for bioconjugation and, ultimately, the design of
      nanocarriers for in vivo applications.

PMID- 16618166
TI  - Influence of temperature on the adsorption of mellitic acid onto kaolinite.
AB  - The adsorption of mellitic acid (benzene-1,2,3,4,5,6-hexacarboxylic acid) onto
      kaolinite was investigated at five temperatures between 10 and 70 degrees C.
      Mellitic acid adsorption increased with increasing temperature at low pH (below
      pH 5.5), but at higher pH, the effect of increasing temperature was to reduce the
      amount adsorbed. Potentiometric titrations were conducted, adsorption isotherms
      were measured over the same temperature range, and the data obtained were used in
      conjunction with adsorption edge and ATR-FTIR spectroscopic data to develop an
      extended constant capacitance surface complexation model of mellitic acid
      adsorption. A single set of reactions was used to model all data at the five
      temperatures studied. The model indicates that mellitic acid sorbs via outer
      sphere complexation to surface hydroxyl (SOH) groups on the kaolinite surface
      rather than to permanent charge sites. The reactions proposed are SOH + L6- + 2H+
      <-->[(SOH2)+(LH)5-]4- and SOH + L(6-) <--> [(SOH)(L)6-]6-. Thermodynamic
      parameters calculated from the temperature dependence of the equilibrium
      constants for these reactions indicate that the adsorption of mellitic acid onto
      kaolinite is accompanied by a large entropy increase.

PMID- 16618167
TI  - Thermodynamic and dynamic characteristics of monoglyceride monolayers penetrated
      by beta-casein.
AB  - In this work, we have analyzed the dynamics of the penetration of beta-casein
      into monoglyceride monolayers (monopalmitin and monoolein) and the structural,
      dilatational, and topographical characteristics of mixed films formed by
      monoglyceride penetrated by beta-casein. Different complementary experimental
      techniques [dynamic tensiometry, surface film balance, Brewster angle microscopy
      (BAM), and surface dilatational rheology] have been used, maintaining the
      temperature constant at 20 degrees C and the pH at 7. The surface pressure of the
      monoglyceride monolayer at the beginning of the penetration process (at pi(i)MP
      and pi(i)MO for monopalmitin and monoolein, respectively) was the variable
      studied. beta-Casein can penetrate into a spread monoglyceride monolayer at every
      surface pressure. The penetration of beta-casein into the monoglyceride monolayer
      with a more condensed structure, at the collapse point of the monoglyceride, is a
      complex process that is facilitated by monoglyceride molecular loss by collapse
      and/or desorption. However, the structural, topographical, and dilatational
      characteristics of the monoglyceride penetrated by beta-casein mixed monolayers
      are essentially dominated by the presence of the monoglyceride (either
      monopalmitin or monoolein) in the mixed film.

PMID- 16618168
TI  - Adsorption studies of a microporous phthalocyanine network polymer.
AB  - The adsorption/desorption of N2 at 77 K and the adsorption from aqueous solution
      at 298 K of four organic probe molecules of different sizes (phenol, 4
      nitrophenol, orange II, naphthol green B) were studied for a phthalocyanine
      network polymer of intrinsic microporosity (PIM) and for an activated carbon
      (Darco 20-40 mesh). N2 sorption analysis gave similar surface areas for the PIM
      and the carbon (610 and 545 m2 g(-1), respectively) but showed differences in
      pore size distribution, the PIM being essentially microporous (pore size < 2 nm),
      with a high proportion of ultramicropores (<0.7 nm), while the carbon had a
      broader pore size distribution, extending into the mesopore region. The carbon
      acted as an adsorbent for all the organic probe molecules studied, while the PIM
      was more selective, adsorbing the smaller molecules but rejecting the large dye
      naphthol green B. The PIM offers selectivity combined with a well-defined
      chemical structure incorporating catalytic sites.

PMID- 16618169
TI  - Wetting of Pb on oxidized micropatterned Si wafers.
AB  - The wetting of lead on silicon wafers with regularly patterned holes, and covered
      by native silica, has been investigated at 610 K under ultrahigh vacuum
      conditions. The advancing and receding macroscopic contact angles have been
      measured by slowly compressing and stretching a liquid lead bridge between two
      identically patterned substrates. These angles are shown to depend on the
      distribution of the holes in the wafers and the continuity of the triple line.

PMID- 16618170
TI  - Numerical analysis of the shapes and energies of droplets on micropatterned
      substrates.
AB  - The shapes and energies of drops on substrates patterned with either holes or
      posts are computed using Surface Evolver software. The holes and posts are
      cylindrical in shape and distributed in a 6-fold symmetric pattern. The wetting
      conditions are such that the liquid does not fill the holes and the interface
      between the drop and the substrate is composite, i.e., partly solid/liquid and
      partly liquid/vapor. The sequence of stable drop configurations with increasing
      volume is analyzed and provides, in part, an explanation for superhydrophobic
      drop spreading.

PMID- 16618171
TI  - Single molecule adsorption at compositionally patterned self-assembled monolayers
      on gold: role of domain boundaries.
AB  - This paper examines the single-molecule adsorption of YOYO-I-labeled lambda-DNA
      at compositionally patterned self-assembled monolayers (SAMs). The interactions
      of fluorescently labeled lambda-DNA molecule with the patterned SAMs, which are
      comprised of different functional groups (i.e., amine-, alcohol-, and acid
      terminated thiolates), were monitored at optically transparent gold films using
      total internal reflection fluorescence microscopy. The role of solution pH,
      lambda-DNA concentration, and domain size was investigated. In addition to
      delineation of the relative adsorption strength as a function of terminal group
      identity (NH2 > COOH > OH), the potential importance of structural defects was
      also revealed. The latter result, found both at the disordered boundaries between
      domains and at adlayers in which structural order was affected by the length of
      the alkyl chain, points to the subtle but preferential adsorption of the "sticky
      ends" of lambda-DNA. These experiments also detected an intriguing dependence of
      adsorption with respect to domain size.

PMID- 16618173
TI  - PNIPAM chain collapse depends on the molecular weight and grafting density.
AB  - This study demonstrates that the thermally induced collapse of end-grafted poly(N
      isopropylacrylamide) (PNIPAM) above the lower critical solution temperature
      (LCST) of 32 degrees C depends on the chain grafting density and molecular
      weight. The polymer was grafted from the surface of a self-assembled monolayer
      containing the initiator (BrC(CH3)2COO(CH2)11S)2, using surface-initiated atom
      transfer radical polymerization. Varying the reaction time and monomer
      concentration controlled the molecular weight, and diluting the initiator in the
      monolayer altered the grafting density. Surface force measurements of the polymer
      films showed that the chain collapse above the LCST decreases with decreasing
      grafting density and molecular weight. At T > LCST, the advancing water contact
      angle increases sharply on PNIPAM films of high molecular weight and grafting
      density, but the change is less pronounced with films of low-molecular-weight
      chains at lower densities. Below the LCST, the force-distance profiles exhibit
      nonideal polymer behavior and suggest that the brush architecture comprises
      dilute outer chains and much denser chains adjacent to the surface.

PMID- 16618172
TI  - Cell migration and polarity on microfabricated gradients of extracellular matrix
      proteins.
AB  - This paper explores the effects of the surface density and concentration profiles
      of extra cellular matrix proteins on the migration of rat intestinal IEC-6 cells.
      Microfluidic devices were used to create linear, immobilized gradients of
      laminin. This study investigated both the impact of the steepness and local
      concentrations on the directedness of cell migration. The bulk concentrations of
      proteins in the feed streams in the mixing device determined the gradient profile
      and the local concentration of laminin in the device. Two sets of gradients were
      used to explore cell migration directedness: (i) gradients with similar change in
      local concentration, i.e., the same gradient steepness, and (ii) different
      gradients with similar local concentrations. Cells migrated up the gradients,
      independent of the steepness of the gradients used in this study. At the same
      local laminin concentration, the migration rate was independent of the gradient
      steepness. However, cell directedness decreased significantly at high laminin
      densities.

PMID- 16618174
TI  - One-dimensional thermotropic dilatation area of lipid headgroups within lamellar
      lipid/DNA complexes.
AB  - Using simultaneous synchrotron small- and wide-angle X-ray diffraction (SWAXD),
      we investigated the thermotropic behavior of a cationic lipid mixture of DOTAP
      DOPC (1,2-dioleoyl-3-trimethylammonium-propane-dioleoylphosphatidylcholine)
      liposomes complexed with calf thymus DNA. The DOTAP-DOPC/DNA complex reacts to
      temperature change by a bilayer compression normal to its surface and an
      expansion of the DNA in the plane of the rod lattice. By applying two independent
      recently developed models, we show here for the first time that the thermotropic
      dilatation area of lipid headgroups within the complexes is not isotropic but
      occurs parallel to the 1D DNA lattice (i.e., along the direction perpendicular to
      the DNA axis). Our results shed light on the role of spatial dimensionality in
      the DNA packing density within lamellar lipoplexes and provide experimental
      evidence that the interaction between DNA molecules confined between lipid
      bilayers can be regarded as a 1D problem.

PMID- 16618175
TI  - High-capacity binding of proteins by poly(acrylic acid) brushes and their
      derivatives.
AB  - Polymeric coatings with high protein-binding capacities are important for
      increasing the output of affinity-based protein purification and decreasing the
      detection limits of antibody microarrays. This report describes the use of thick
      poly(acrylic acid) (PAA) brushes to immobilize as much as 80 monolayers of
      protein. The brushes were prepared using a recently developed procedure that
      allows polymerization of 100-nm-thick poly(tert-butyl acrylate) films from a
      surface in just 5 min along with hydrolysis of these films to PAA in 15 min.
      Covalent binding of bovine serum albumin (BSA) to PAA brushes that were activated
      using standard coupling agents, however, resulted in immobilization of less than
      two monolayers of BSA because of competitive hydrolysis of the esters in the
      activated film. In contrast, derivatization of PAA with nitrilotriacetate (NTA)
      Cu2+ complexes yielded films capable of binding many monolayers of protein via
      metal-ion affinity interactions. For example, derivatization of 55-nm-thick PAA
      films with NTA-Cu2+ allowed immobilization of about 15 monolayers (5.8 microg/cm2
      or 58 nm) of BSA. The binding capacity was even higher for myoglobin (7.7
      microg/cm2) and anti-IgG (9.6 microg/cm2). Remarkably, electrostatic adsorption
      of lysozyme in 55-nm-thick, underivatized PAA resulted in as much as 80
      monolayers (16.2 microg/cm2 or 162 nm) of adsorbed protein. Polymer synthesis,
      derivatization, and swelling, as well as BSA immobilization kinetics and
      thermodynamics were characterized using reflectance FT-IR spectroscopy,
      ellipsometry, and protein assays.

PMID- 16618176
TI  - Exploitation of the coil-globule plasmid DNA transition induced by small changes
      in temperature, pH salt, and poly(ethylene glycol) compositions for directed
      partitioning in aqueous two-phase systems.
AB  - In this study, the interplay of two linked equilibria is examined, one concerning
      an aqueous two-phase system (ATPS) composed of poly(ethylene glycol) (PEG) and
      salt employed to partition plasmid DNA (pDNA), and the other a potential
      structural transition of pDNA depending on PEG and salt concentration and other
      system parameters. The boundary conditions for pDNA partitioning are set by PEG
      and salt concentrations, PEG molecular weight, pH, and temperature. While
      investigating these parameters, it was found that a small increase/decrease of
      the respective values led to a drastic and significant change in pDNA behavior.
      This behavior could be attributed to a coil-globule transition of the pDNA
      triggered by the respective phase conditions. The combination of this structural
      change, aggregation effects linked to the transition process, and the
      electrostatic potential difference found in PEG-salt systems thus offers a
      sensitive way to separate nucleic acid forms on the basis of their unique
      property to undergo coil-globule transitions under distinct system properties.

PMID- 16618177
TI  - Lateral phase separation in lipid-coated microbubbles.
AB  - In the design of lipid-coated microbubble ultrasound contrast agents for
      molecular imaging and targeted drug delivery, the surface distribution of the
      shell species is important because it dictates such properties as ligand
      location, brush coverage, and amount of drug loading. We used a combination of
      spectroscopy and microscopy techniques to test the prevailing notion that the
      main phosphatidyl choline (PC) and lipopolymer species are completely miscible
      within the monolayer shell. NMR spectroscopy showed that the shell composition is
      roughly equivalent to the bulk lipid ratio. FTIR spectroscopy showed a sharp
      melting peak corresponding to the main phase-transition temperature of the main
      PC species, with no observed pretransitions while scanning from room temperature,
      indicating a single PC-rich ordered phase. Electron and fluorescence microscopy
      showed a heterogeneous microstructure with dark (ordered) domains and bright
      (disordered) regions. Domain formation was thermotropic and reversible.
      Fluorescent labeling of the lipopolymer following shell formation showed that it
      partitions preferentially into the disordered interdomain regions. The ordered
      domains, therefore, are composed primarily of PC, and the disordered interdomain
      regions are enriched in lipopolymer. Phase heterogeneity was observed at all
      lipopolymer concentrations (0.5 to 20 mol %), and the degree of phase separation
      increased with lipopolymer content. The composition and temperature dependence of
      the microstructure indicates that phase separation is driven thermodynamically
      rather than being a kinetically trapped relic of the shell-formation process. The
      overall high variation in microstructure, including the existence of anomalous
      three-phase coexistence, highlights the nonequilibrium (history-dependent) nature
      of the monolayer shell.

PMID- 16618180
TI  - Tricarbonyls of low-coordinated Au(0) atoms in zeolite-supported gold
      nanoparticles: Evidence from infrared and X-ray absorption spectroscopies.
AB  - Mononuclear gold complexes in zeolite NaY were synthesized from initially
      physisorbed Au(CH3)2(C5H7O2) and characterized by X-ray absorption and infrared
      spectra recorded as the samples were exposed to flowing CO. X-ray absorption
      spectra demonstrate the formation of zero-valent gold nanoparticles during the CO
      treatment. Three new nu(CO) bands grew in during this treatment, at 2070, 2033,
      and 2000 cm(-1), characteristic of carbonyls of Au0. Because the relative
      intensities of these bands decreased monotonically when the flow of CO was
      replaced by flowing He, it is inferred that they correspond to a single Au0(CO)3
      species, on low-coordinated Au atoms. This is the first example of an Au0(CO)3
      species.

PMID- 16618181
TI  - Novel 3-D structures in polymer films by coupling external and internal fields.
AB  - A route to produce novel three-dimensional structures in thin films is
      demonstrated. Such structures are most difficult to produce in a simple manner
      without the use of multiple fabrication steps. Here, we show the generation of 3
      D cage-type structures using a combination of electrohydrodynamic instabilities
      and dewetting in a polymer/polymer/air trilayer. Removal of one of the components
      by use of a selective solvent or by degradation of one of the components reveals
      the formation of a three-dimensional structure, where one polymer is encased in
      the other. Thus, by coupling an external field with a surface field inherent to
      the polymers, a novel fabrication strategy is shown that has clear applications
      in microfluidics and microelectromechanical systems with extensions to patterned
      surfaces and structured fluids, like block copolymers.

PMID- 16618178
TI  - Using scanning electrochemical microscopy (SECM) to measure the electron-transfer
      kinetics of cytochrome c immobilized on a COOH-terminated alkanethiol monolayer
      on a gold electrode.
AB  - Cytochrome c was electrostatically immobilized onto a COOH-terminated alkanethiol
      self-assembled monolayer (SAM) on a gold electrode at ionic strengths of less
      than 40 mM. Scanning electrochemical microscopy (SECM) was used to simultaneously
      measure the electron transfer (ET) kinetics of the bimolecular ET between a
      solution-based redox mediator and the immobilized protein and the tunneling ET
      between the protein and the underlying gold electrode. Approach curves were
      recorded with ferrocyanide as a mediator at different coverages of cytochrome c
      and at different substrate potentials, allowing the measurement of k(BI) = 2 x
      10(8) mol(-1) cm3 s(-1) for the bimolecular ET and k degrees = 15 s(-1) for the
      tunneling ET. The kinetics of ET was also found to depend on the immobilization
      conditions of cytochrome c: covalent attachment gave slightly slower tunneling ET
      values, and a mixed CH3/COOH-terminated ML gave faster tunneling ET rates. This
      is consistent with previous studies and is believed to be related to the degree
      of mobility of cyt c in its binding configuration and its orientation with
      respect to the underlying electrode surface.

PMID- 16618179
TI  - Dendritic-like streptavidin/alkaline phosphatase nanoarchitectures for amplified
      electrochemical sensing of DNA sequences.
AB  - This study describes the development and characterization of a novel dendritic
      like signal amplification pathway. Such an analytical strategy relies on the use
      of streptavidin and biotinylated alkaline phosphatase, which can be simply and
      conveniently self-assembled to build nanoarchitectures rich in enzyme labels. The
      performance of this enzyme-based amplification route was demonstrated in
      connection with the electrochemical sensing of DNA sequences. Compared to the
      commercially available streptavidin-conjugated alkaline phosphatase labels, a
      single generation of the streptavidin/biotinylated alkaline phosphatase assembly
      allowed a 15-20-fold enhancement of the electroanalytical signals. The higher
      sensitivity allowed by the dendritic-like route was attributed to the lower
      steric hindrance of the proteins employed for this amplification path. As low as
      50 pmol/L of a 388-bp-long amplicon identifying Salmonella spp. was easily
      detected. The experimental results additionally demonstrated that the sensitivity
      of the method could be further increased in a linear fashion with the number of
      protein-enzyme generations.

PMID- 16618182
TI  - Versatile routes toward functional, water-soluble nanoparticles via
      trifluoroethylester-PEG-thiol ligands.
AB  - This paper reports the synthesis of a trifluoroethylester-PEG-thiol ligand (TFEE
      PEG-SH) and its use to create water-soluble, chemically functional Au metal and
      FePt magnetic nanoparticles. The trifluoroethylester terminus facilitates
      attachment of any primary-amine-containing molecule via amide bond formation at
      room temperature without the use of coupling agents. Three possible routes of
      nanoparticle functionalization are demonstrated: synthesis of Au nanoparticles in
      the presence of functionalized R-PEG-SH; ligand-exchange of R-PEG-SH onto both Au
      and FePt nanoparticles; and exchange of TFEE-PEG-SH onto Au nanoparticles
      followed by subsequent amide condensation. A series of primary-amine-containing
      molecules, including biotin and fluorescamine, are easily attached to the water
      soluble particles, and the resulting materials are characterized by NMR, UV
      visible absorption, and emission spectroscopies.

PMID- 16618183
TI  - Self-assembly and physicochemical and rheological properties of a polysaccharide
      surfactant system formed from the cationic biopolymer chitosan and nonionic
      sorbitan esters.
AB  - The natural cationic polysaccharide chitosan was mixed with the nonionic
      surfactants sorbitan monolaurate, sorbitan monooleate, or sorbitan triooleate to
      produce a biopolymer-surfactant system with unique properties. The mixtures of
      chitosan and surfactant formed emulsion-like solutions and/or creams. The known
      properties of the components were considered (i.e., hydrophile-lipophile balance,
      molecular weight, structure, and density), and various physicochemical and
      rheological properties of the mixtures were measured. Specifically, the critical
      micelle concentration of the sorbitan esters in a chitosan solution was measured
      using both surface tension and fluorescence-based methods. The concentration
      dependent morphologies of the aggregates within the chitosan-surfactant solutions
      were evaluated by optical microscopy and dynamic light scattering. A schematic
      depicting the possible molecular arrangement of chitosan and surfactant within
      the various formulations was produced from consideration of the experimental
      findings. The degree of interaction between chitosan and the individual
      surfactants was assessed by FTIR analysis. The rheological properties of the
      chitosan-surfactant emulsions were also investigated and found to be related to
      the observed morphologies. Overall, clear composition-property relationships were
      established for these chitosan-surfactant systems which have potential
      applications in the food and pharmaceutical industries.

PMID- 16618185
TI  - Deformable hollow hybrid silica/siloxane colloids by emulsion templating.
AB  - A procedure to obtain hollow colloidal particles has been developed using an
      emulsion templating technique. Monodisperse silicone oil droplets were prepared
      by hydrolysis and polymerization of dimethyldiethoxysilane monomer and
      incorporated in a solid shell using tetraethoxysilane. Hollow shells were
      obtained by exchange of the core. The formation of the oil droplets was
      investigated using static light scattering and 29Si solution NMR, and the hollow
      shells were characterized by electron microscopy and static light scattering.
      Details on the composition of the shell material were obtained from energy
      dispersive X-ray analysis and 29Si solid state NMR, revealing that the shells
      consist of a hybrid cross-linked network of silica and siloxane units. Confocal
      microscopy was used to show that the shells are permeable to small dye molecules.
      The thickness of the coating can be easily varied from a few nanometers upward.
      Depending on the ratio of shell thickness to particle radius, three types of
      hollow shells can be distinguished depending on the way in which they buckle upon
      drying. We designate them as microspheres, microcapsules, and microballoons. As a
      result of their monodispersity, these particles can be used for making 3D-ordered
      materials.

PMID- 16618184
TI  - Soluble-insoluble-soluble transitions of aqueous poly(N-vinylacetamide-co-acrylic
      acid) solutions.
AB  - Several poly(N-vinylacetamide-co-acrylic acid)s with various copolymer
      compositions have been synthesized, and their unique phase-transition behavior in
      aqueous salt (Na2SO4 or NaCl) solutions was investigated. Copolymers containing
      more than 51 mol % N-vinylacetamide (NVA) show reentrant soluble-insoluble
      soluble transitions with increasing temperature. The soluble-insoluble transition
      temperature (T(p1)) increased linearly with increasing NVA content, whereas the
      insoluble-soluble transition temperature (T(p2)) was almost constant irrespective
      of the NVA content. Potentiometric titration of the copolymer solutions suggested
      that the acrylic acid (AA) carboxyl groups form hydrogen bonds with the NVA amide
      groups even under soluble conditions. Dehydration of the NVA amides and their
      consequent hydrogen bonding with the AA carboxyl groups during the soluble
      insoluble transition process was indicated by FTIR measurements. Addition of salt
      (Na2SO4 or NaCl) to the aqueous media reduces the solvent quality and enhances
      the intra- and interchain interactions of the copolymers. Thus, T(p1) was
      observed to decrease and T(p2) was observed to increase with increasing salt
      concentration. However, the addition of urea to the media reverses the
      concentration dependence of T(p1) and T(p2) by disturbing the intra- and
      interchain interactions of the copolymers.

PMID- 16618186
TI  - Photoresponsive properties of poly(N-isopropylacrylamide) hydrogel partly
      modified with spirobenzopyran.
AB  - A photoresponsive hydrogel was prepared by radical copolymerization of N
      isopropylacrylamide, a vinyl monomer having a spirobenzopyran residue and cross
      linker. By the observation of photoresponsive shrinking and the conductance
      change, it was confirmed that the hydrogel in an acidic condition exhibited
      drastic and rapid volume shrinkage and proton dissociation when it was irradiated
      with blue light. Further, to examine its application to the mass transfer
      control, we prepared a photo- and thermoresponsive gate membrane by introducing
      this photoresponsive hydrogel to the surface of a porous membrane. As the first
      demonstration of the photocontrol of membrane permeation for liquid, it was
      observed that its permeability for 1 mM HCl aqueous solution increased by 2 times
      in response to the blue light irradiation, and this photoresponse of the
      permeability was confirmed to be repeatable.

PMID- 16618188
TI  - Organically capped silicon nanoparticles with blue photoluminescence prepared by
      hydrosilylation followed by oxidation.
AB  - A facile method of preparing stable blue-emitting silicon nanoparticles that are
      dispersible in common organic solvents is presented. Oxidation of yellow-emitting
      silicon nanoparticles with an organic monolayer grafted to their surface, using
      either UV irradiation in solution or heating in air, converted them to blue
      emitting particles. The evolution of the PL spectrum and infrared absorption
      spectrum of the particles was followed during the oxidation process. The PL
      spectrum showed a decrease in the PL emission peak near 600 nm and the appearance
      and increase in intensity of a PL emission peak near 460 nm rather than a smooth
      blue shift of the emission spectrum from yellow to blue. The organic monolayer
      grafted to the particle surface was not degraded by this oxidation process, as
      demonstrated by FTIR and NMR spectroscopy. Similar results were achieved for
      particles with styrene, 1-octene, 1-dodecene, and 1-octadecene grafted to their
      surface, demonstrating that it is the silicon nanocrystal, and not the organic
      component, that is essential to this process. The organic monolayer allows the
      nanoparticles to form stable, clear colloidal dispersions in organic solvents and
      provides for the possibility of further chemical functionalization of the
      particles. Combined with previous work on organically grafted silicon
      nanoparticles with green through near-infrared emission, this enables the
      efficient and scalable preparation of stable colloidal dispersions of organically
      grafted silicon nanoparticles with emission spanning the entire visible spectrum.

PMID- 16618187
TI  - Surface modification of silica nanoparticles to reduce aggregation and
      nonspecific binding.
AB  - In this article, a systematic study of the design and development of surface
      modification schemes for silica nanoparticles is presented. The nanoparticle
      surface design involves an optimum balance of the use of inert and active surface
      functional groups to achieve minimal nanoparticle aggregation and reduce
      nanoparticle nonspecific binding. Silica nanoparticles were prepared in a water
      in-oil microemulsion and subsequently surface modified via cohydrolysis with
      tetraethyl orthosilicate (TEOS) and various organosilane reagents. Nanoparticles
      with different functional groups, including carboxylate, amine,
      amine/phosphonate, poly(ethylene glycol), octadecyl, and carboxylate/octadecyl
      groups, were produced. Aggregation studies using SEM, dynamic light scattering,
      and zeta potential analysis indicate that severe aggregation among amine-modified
      silica nanoparticles can be reduced by adding inert functional groups, such as
      methyl phosphonate, to the surface. To determine the effect of various surface
      modification schemes on nanoparticle nonspecific binding, the interaction between
      functionalized silica nanoparticles and a DNA chip was also studied using
      confocal imaging/fluorescence microscopy. Dye-doped silica nanoparticles
      functionalized with octadecyl and carboxylate groups showed minimal nonspecific
      binding. Using these surface-modification schemes, fluorescent dye-doped silica
      nanoparticles can be more readily conjugated with biomolecules and used as highly
      fluorescent, sensitive, and reproducible labels in bioanalytical applications.

PMID- 16618189
TI  - Silica encapsulation of hydrophobically ligated PbSe nanocrystals.
AB  - Spherical PbSe@SiO2 nanoparticles have been successfully synthesized within
      reverse micelles via metal alkoxide hydrolysis and condensation within a
      microemulsion system. These core-shell nanoparticles were characterized by
      transmission electron microscopy (TEM), NIR absorption spectroscopy, energy
      dispersive X-ray analysis, and TEM electron diffractions. It shows that the
      obtained core-shell structures have a spherical shape with narrow size
      distribution (average size approximately 35 nm) and smooth surfaces. The size of
      the particles and the thickness of the shells can be controlled by manipulating
      the relative rates of the hydrolysis and condensation reactions of
      tetraethoxysilane (TEOS) within the microemulsion.

PMID- 16618190
TI  - From exponential to linear growth in polyelectrolyte multilayers.
AB  - There exist two types of polyelectrolyte multilayers: those whose thickness
      increases linearly with the number of deposition steps, which are nicely
      structured, and those whose thickness increases exponentially, which resembles
      hydrogels. This simple picture has recently slightly evolved with the finding
      that some exponentially growing films enter into a linear growth phase after a
      certain number of deposition steps. In this study, we investigate the buildup
      process of hyaluronic acid/poly(L-lysine) (HA/PLL) multilayers that constitute
      one of the best known exponentially growing systems. The films are built by using
      two deposition methods: the well-known dipping method and the more recent
      spraying method where the polyelectrolyte solutions are sprayed alternately onto
      a vertical substrate. The goal of this study is twofold. First, we investigate
      the influence of the main parameters (i.e., spraying rate and spraying time) of
      the spraying method on the film growth process. We find that, as for the dipping
      method, the film thickness first evolves exponentially with the number of
      deposition steps, and after a given number of deposition steps, it follows a
      linear evolution. We find that similar behavior is observed with the dipping
      method. Second, because the spraying method allows the very fine variation of the
      different parameters of the buildup, we use this method to investigate the
      exponential-to-linear transition. We find that this transition always takes place
      after about 12 deposition steps whatever the values of the parameters controlling
      the deposition process. We discuss our results in light of a model proposed by
      Hubsch et al. (Hubsch, E.; Ball, V.; Senger, B.; Decher, G.; Voegel, J. C.;
      Schaaf, P. Langmuir 2004, 20, 1980-1985) and later by Salomaki et al. (Salomaki,
      M.; Vinokurov, I. A.; Kankare, J. Langmuir 2005, 21, 11232-11240) in which it is
      assumed that the exponential-to-linear transition is due to a film restructuring
      that progressively forbids the diffusion of one of the polyelectrolytes
      constituting the film over part of the film. This "forbidden" zone then grows
      with the number of deposition steps so that the outer zone of the film that is
      still concerned with diffusion keeps a constant thickness and moves upward as the
      total film thickness increases.

PMID- 16618191
TI  - Polyaniline/Au composite hollow spheres: synthesis, characterization, and
      application to the detection of dopamine.
AB  - Polyaniline (PANI)/Au composite hollow spheres were successfully synthesized
      using polystyrene/sulfonated polystyrene core/shell gel particle templates. The
      PANI shell thickness and the number of Au nanoparticles decorating the PANI could
      be controlled effectively by adjusting the experimental conditions. The
      morphology, composition, and optical properties of the resulting products were
      characterized by scanning electron microscopy, transmission electron microscopy,
      X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy,
      Fourier transform infrared spectroscopy, and ultraviolet-visible absorption
      spectra. It was found that the electrical conductivity of the PANI/Au composite
      hollow spheres was more than 3 times higher than that of the pure PANI hollow
      spheres. Furthermore, PANI/Au composites were immobilized on the surface of a
      glassy carbon electrode (GCE) and applied to construct a sensor. The obtained
      PANI/Au-modified GCEs showed one pair of redox peaks and high catalytic activity
      for the oxidation of dopamine. The possible formation mechanism of the PANI/Au
      composite hollow spheres was also discussed.

PMID- 16618192
TI  - Direct synthesis of zirconia aerogel nanoarchitecture in supercritical CO2.
AB  - The objective of the present study was to synthesize porous ZrO2 aerogels with a
      nanostructure via a direct sol-gel route in the green solvent supercritical
      carbon dioxide (scCO2). The synthesis involved the coordination and
      polycondensation of a zirconium alkoxide using acetic acid in CO2, followed by
      scCO2 drying and calcination. Either a translucent or opaque monolith was
      obtained, which was subsequently characterized by electron microscopy, X-ray
      diffraction, thermal analysis, N2 physisorption, and infrared spectroscopy
      analysis. The electron microscopy results showed that the translucent monolithic
      ZrO2 exhibited a well-defined mesoporous structure, while the opaque monolith,
      formed using added alcohol as a cosolvent, was composed of loosely compacted
      nanospherical particles with a diameter of ca. 20 nm. After calcination at 400
      and 500 degrees C, X-ray diffraction results indicated that the ZrO2 exhibited
      tetragonal and/or monoclinic phases. In situ infrared spectroscopy results showed
      the formation of a Zr-acetate coordinate complex at the initial stage of the
      polycondensation, followed by further condensation of the complex into
      macromolecules.

PMID- 16618193
TI  - Polymeric nano/microcapsules of liquid perfluorocarbons for ultrasonic imaging:
      physical characterization.
AB  - Ultrasonic imaging is a widely available, noninvasive, and cost-effective
      diagnostic modality, but vessels smaller than 200 mum in diameter are impossible
      to visualize. Commercial ultrasound contrast agents (UCAs), consisting of
      encapsulated gas microbubbles injected intravenously, enable only a qualitative
      visualization of the microvascularization for a short period of time since they
      are rather unstable. In a strategy to develop more stable UCAs, we designed a
      process to obtain nano/microcapsules with a single core of liquid
      perfluorocarbons within a biodegradable polymeric shell of homogeneous thickness.
      The polymer shell should improve the stability of the capsules as compared to
      UCAs stabilized by a monomolecular layer, while the acoustic impedance of the
      perfluorocarbons should ensure their echogenicity. These capsules have been
      optimized to encapsulate several liquid perfluorocarbons: perfluorohexane,
      perfluorodecalin, and perfluorooctyl bromide. The system is rather versatile: the
      mean size of the capsules can be adjusted between 70 nm and 25 microm and the
      thickness-to-radius ratio (T/R) can be easily modulated by simply modifying the
      polymer-to-perfluorocarbon ratio. T/R does not depend on the size of the capsules
      and is between 0.2 and 0.6. The dependence of the echogenic properties of the
      capsules with their size and their T/R has yet to be studied experimentally
      before this system can be evaluated in vivo.

PMID- 16618194
TI  - Preparations and optical properties of ordered arrays of submicron gel particles:
      interconnected state and trapped state.
AB  - Two types of thermosensitive opal-structured hydrogel systems, "interconnected"
      and "trapped" gel particle arrays, were newly developed by extremely simple
      methods using silica colloidal crystal as a template. Although both systems
      diffract visible light following Bragg's law combined with Snell's law, the
      temperature dependences of their optical properties were quite different. The
      "interconnected" array exhibited a reversible change in the peak values of the
      reflection spectra, mainly determined by the swelling ratio of the hydrogel, as a
      function of the water temperature. Since the swelling ratio is dominant over the
      peak value, we can observe water temperature through the color of the
      interconnected type of gel membrane. The "trapped" array revealed a reversible
      change in the peak intensity of the reflection spectra with the change in
      temperature, whereas no change in the peak position was observed. We can
      interpret this phenomenon in the following ways. As the rise in temperature
      causes a decrease in the water content of the NIPA gel particles, the gel
      particles becomes stickier on the cavity wall of polystyrene PPM. This may induce
      a disturbance in the ordered array of the gel particles and form many layers of
      rough surfaces in the inverse opal structure of the PPM. This situation may lead
      to the stronger diffused reflection of light from the gel particles, resulting in
      the decrease in peak intensity at higher temperatures.

PMID- 16618196
TI  - Electrochemically induced atom-by-atom growth of ZnS thin films: a new approach
      for ZnS co-deposition.
AB  - Ultrathin films of ZnS were grown on Au (111) substrates using a novel, simple co
      deposition method and characterized using X-ray diffraction (XRD), atomic force
      microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and UV-visible
      spectroscopy. Cyclic voltammograms were used to determine approximate deposition
      potentials for co-deposition. XRD shows that the material growth is highly
      preferential with (111) orientation. Both AFM and XRD data indicate that the ZnS
      growth mechanism starts by the formation of rounded nanoparticles at the surface
      and then continues by lateral and vertical growth to form flat square
      crystallites of ZnS. UV-vis spectra taken for the ZnS thin films with various
      thicknesses, which is related to deposition time, shows that the band gap of the
      ZnS decreases as the film thickness increases.

PMID- 16618195
TI  - Bicontinuous cubic phase of monoolein and water as medium for electrophoresis of
      both membrane-bound probes and DNA.
AB  - Porous hydrogels such as agarose are commonly used to analyze DNA and water
      soluble proteins by electrophoresis. However, the hydrophilic environment of
      these gels is not suitable for separation of important amphiphilic molecules such
      as native membrane proteins. We show that an amphiphilic liquid crystal of the
      lipid monoolein and water can be used as a medium for electrophoresis of
      amphiphilic molecules. In fact, both membrane-bound fluorescent probes and water
      soluble oligonucleotides can migrate through the same bicontinuous cubic crystal
      because both the lipid membrane and the aqueous phase are continuous. Both types
      of analytes exhibit a field-independent electrophoretic mobility, which suggests
      that the lipid crystal structure is not perturbed by their migration. Diffusion
      studies with four membrane probes indicate that membrane-bound analytes
      experience a friction in the cubic phase that increases with increasing size of
      the hydrophilic headgroup, while the size of the membrane-anchoring part has
      comparatively small effect on the retardation.

PMID- 16618197
TI  - Electric field driven protonation/deprotonation of self-assembled monolayers of
      acid-terminated thiols.
AB  - Using electrochemical impedance spectroscopy (EIS), we provide an explanation for
      the pH dependence of the voltammetric peak height for the electric-field-driven
      protonation and deprotonation of carboxylic acid-terminated thiol self-assembled
      monolayers (SAMs). The current flowing through the interface can be divided into
      a purely capacitive current and a protonation/deprotonation current that is
      directly related to the rate of change of the SAM's protonation (or
      deprotonation). We demonstrate that at applied potentials close to those
      corresponding to half-ionization of the SAM and pHs near the pK(1/2), the
      equivalent circuit describing the interface consists of a Helmholtz film capacity
      in parallel with a "protonation/deprotonation" impedance which is further shown
      to be a series combination of a resistor, Rp, and capacitor Cp. Explicit
      expressions for Rp and Cp are derived in terms of the rate constants for the
      forward (protonation) and reverse (deprotonation) reactions. Simulated EIS data
      demonstrate the agreement between our model of the interface and experimental
      impedance and voltammetric data.

PMID- 16618198
TI  - pH- and ionic strength-controlled cation permselectivity in amine-modified
      nanoporous opal films.
AB  - The influence of pH and ionic strength on permselective transport in nanoporous
      opal films prepared from 440 nm silica spheres was investigated by cyclic
      voltammetry in aqueous and acetonitrile solutions. Three-layer opal films were
      deposited from a 1.5 wt % colloidal solution of silica spheres onto 25-microm
      diameter Pt microdisk electrodes shrouded in glass. The films were chemically
      modified by immersing them in a dry acetonitrile solution of 3-aminopropyl
      triethoxysilane. When the surface amino groups of the modified opal films are
      protonated and there is little or no supporting electrolyte present in solution,
      the flux of cationic redox species through the opal membrane is blocked because
      of electrostatic repulsion. The permselectivity is pH-dependent and can be
      modulated by adjusting the Debye screening length within the nanopores of the
      opal by changing the ionic strength of the contacting solution.

PMID- 16618199
TI  - Electrochemical properties of self-assembled monolayers of polyaniline: effects
      of the thiol substituent and reduced dimensionality.
AB  - Self-assembled monolayers and bulk films of thioanilines, polymerized on gold and
      platinum surfaces, have been characterized and compared to bulk polyaniline
      (PANI) films. In a previous study [Kuwabata; et al. Langmuir 1999, 15, 6807
      6812], only one redox couple was observed in the cyclic voltammetric profile of a
      polymerized monolayer of thioaniline on gold, in contrast to the known profiles
      of bulk PANI, which exhibit two couples. We observe two couples in both a
      polymerized thioaniline monolayer and a bulk polythioaniline (S-PANI) film, but
      the 200 mV window between the couples (the width of the region of high
      conductivity) in the S-PANI films is much smaller than the 600 mV window in bulk
      PANI. We ascribe this difference to the presence of the thiol substituent. The
      windows of high conductivity of the polymerized thioaniline monolayer and the
      bulk S-PANI film are the same within the limits of our experiment, implying that
      the difference in the dimensionality of the films (a 2D monolayer vs 3D bulk
      films) has a limited effect on the films' voltammetric profiles.

PMID- 16618200
TI  - Ferrocenylalkylthiolates as a probe of heterogeneity in binary self-assembled
      monolayers on gold.
AB  - The oft-cited complexity of tethered ferrocene electrochemistry in single
      component (FcRS-) or binary (FcRS-/CH3R'S-) self-assembled monolayers (SAMs) on
      gold has been investigated. The complex voltammetry is shown to be linked to
      local electrostatics caused by the formation of the ferrocenium ion. This
      conclusion is reached by studying model effects in binary SAMs, where a cationic
      alkylthiolate (H3N+ C11S-Au) is mixed with FcC12S-Au. A fitting procedure
      involving both a Gaussian and a Lorentzian distribution is used for deconvolution
      of the two peaks which are consistently observed in the SAMs when chi(Fc)surf >
      or = 0.2. The lower-potential (E degrees ' = 250 mV) and higher-potential (E
      degrees ' = 350 mV) voltammetric peaks are assigned to Fc moieties in "isolated"
      and "clustered" states, respectively. Use of this method to better understand SAM
      structure is demonstrated by distinguishing the degree of homogeneity in two
      binary SAMs of similar composition.

PMID- 16618202
TI  - Characterization of transverse channel concentration profiles obtainable with a
      class of microfluidic networks.
AB  - We analyze mathematically a previously reported class of passive microfluidic
      mixing networks. The networks produce nonhomogeneous concentrations in the output
      channel, resulting in diverse concentration profiles. We formally prove that all
      profiles obtainable with this class of networks can be described as polynomials
      of degree no higher than the number of input channels less one. We derive
      explicit formulas for the calculation of resultant output concentration profiles
      and conversely for the calculation of input concentrations needed to obtain set
      output profiles.

PMID- 16618201
TI  - Surface engineering of poly(dimethylsiloxane) microfluidic devices using
      transition metal sol-gel chemistry.
AB  - We report the coating of poly(dimethylsiloxane) (PDMS) microchannels using
      transition metal sol-gel chemistry and the subsequent characterization of the
      coatings. The channels were created using soft polymer lithography, and three
      metal alkoxide sol-gel precursors were investigated, titanium isopropoxide,
      zirconium isopropoxide, and vanadium triisobutoxide oxide. The metal alkoxides
      were diffused into the sidewalls of a PDMS channel and subsequently hydrolyzed
      using water vapor. This procedure resulted in the formation of durable metal
      oxide surfaces of titania, zirconia, or vanadia. The resulting surfaces were
      characterized using contact angle, X-ray photoelectron spectroscopy (XPS), Raman,
      transmission electron microscopy (TEM), scanning electron microscopy (SEM),
      atomic force microscopy (AFM), and electroosmotic mobility (EOM) measurements.
      All of the metal oxide-modified PDMS surfaces were significantly more hydrophilic
      than native PDMS. Contact angles for the coatings were 90 degrees for PDMS-ZrO2,
      61 degrees for PDMS-TiO2, and 19 degrees for PDMS-vanadia. XPS showed the
      presence of titania, zirconia, and vanadia on the PDMS surface. XPS spectra also
      showed no chemical modification of the PDMS after the in situ deposition of the
      particles either in the Si-O, Si-C, or C-H bonds of the PDMS. The particles
      deposited in situ were imaged with TEM and were found to be homogeneously
      distributed throughout the bulk of the PDMS. EOM measurements of the inorganic
      coatings were stable over a period of at least 95 days. Both cathodic and anodic
      EOMs could be generated depending upon buffer pH used. The points of net zero
      charge for PDMS-TiO2, PDMS-ZrO2, and PDMS-vanadia channels were calculated using
      EOM versus pH measurements and were found to be 4.1 +/- 0.25, 6.1 +/- 0.2, and
      7.0 +/- 0.43, respectively. In addition to modifying PDMS channels with inorganic
      coatings, these inorganic coatings were derivatized with various organic
      functionalities including oligoethylene oxide (OEO), amino, perfluoro, or
      mercapto groups using silane chemistry. Contact angle measurements for perfluoro,
      mercapto, amino, and OEO-coated surfaces yielded contact angles of 120 degrees ,
      76 degrees , 45 degrees , and 23 degrees , respectively. These contact angles did
      not change over the period of 95 days. OEO-coated channels reduced the EOM by 50%
      from native PDMS-TiO2 to 0.9 +/- 0.05 x 10(-4) cm2/V.s (n = 5, 5.5% RSD).

PMID- 16618204
TI  - A new cell line from the wax moth Galleria mellonella Linne (Lepidoptera:
      Pyralididae).
AB  - A cell line derived from the larval-fat body tissues of the wax moth, Galleria
      mellonella Linne, was established in MGM-450 medium. The cells grew in suspension
      and were mainly spherical in shape. Population doubling time was between 1.4 and
      1.7 d over a range of 15 to 35 degrees C, and the maximum growth rate was at 25
      degrees C. The chromosome number ranged from 70-239, with a mode of 170. The
      cells were sensitive to 20-hydroxyecdysone, which stimulated their growth and
      induced morphological changes. The cell line was designated GaMe-LF1.

PMID- 16618205
TI  - Self-propagating calciferous particles detected in a human cell line Kasumi-6
      (JCRB1024).
AB  - Tiny particles were found in the medium in the presence of the human leukemia
      cell line Kasumi-6. The particles were separated from human cells by filtration
      and incubated in RPMI1640 supplemented with 10% fetal calf serum at 37 C. The
      particles increased in number very slowly in the liquid medium but did not reveal
      any biological activity. Transmission electron microscopy of the particles showed
      a spheroid or ovoid shape in ultrathin section. No specific polypeptides from the
      purified particles were detected by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), except for bovine fetuin that adsorbed to the surface
      of the particles. X-ray diffractometry as well as Fourier transform infrared
      spectrometry suggested the particles consisted of hydroxyapatite. The mechanism
      of self-propagation of the hydroxyapatite particles in liquid medium is currently
      unknown. This type of particle has been overlooked for a long period because it
      is noncultivable. It will be necessary to examine its biological effects to the
      cultured cells.

PMID- 16618206
TI  - Heterogeneous nuclear transfer embryos reconstructed by bovine oocytes and camel
      (Camelus bactrianus) skin fibroblasts and their subsequent development.
AB  - This study reconstructed heterogeneous embryos using camel skin fibroblast cells
      as donor karyoplasts and the bovine oocytes as recipient cytoplasts to
      investigate the reprogramming of camel somatic cell nuclei in bovine oocyte
      cytoplasm and the developmental potential of the reconstructed embryos. Serum
      starved skin fibroblast cells, obtained from adult camel, were electrically fused
      into enucleated bovine metaphase II (MII) oocytes that were matured in vitro. The
      fused eggs were activated by Inomycin with 2 mM/ml 6-dimethylaminopurine. The
      activated reconstructed embryos were cocultured with bovine cumulus cells in
      synthetic oviduct fluid supplemented with amino acid (SOFaa) and 10% fetal calf
      serum for 168 h. Results showed that 53% of the injected oocytes were
      successfully fused, 34% of the fused eggs underwent the first egg cleavage, and
      100% of them developed to four- or 16-cell embryo stages. The first completed
      cleavage of xenonuclear transfer camel embryos occurred between 22 and 48 h
      following activation. This study demonstrated that the reconstructed embryos
      underwent the first embryonic division and that the reprogramming of camel
      fibroblast nuclei can be initiated in enucleated bovine MII oocytes.

PMID- 16618207
TI  - Ethanolamine modulates DNA synthesis through epidermal growth factor receptor in
      rat primary hepatocytes.
AB  - Ethanolamine (Etn) stimulates hepatocyte proliferation in vivo and in vitro;
      however, the physiological function of Etn in hepatocytes has yet to be
      elucidated. In the present study, we examined the effect of Etn using a primary
      culture of rat hepatocytes. The level of membrane phosphatidylethanolamine (PE)
      significantly decreased when the hepatocytes were cultured without Etn but
      increased to the level found in the liver when the culture medium was
      supplemented with 20- 50 microM Etn. Moreover, Etn stimulated DNA synthesis in a
      dose-dependent manner and had a synergistic effect with epidermal growth factor
      (EGF). A binding assay and Western blotting showed that the number of EGF
      receptors was 22- 30% lower in cells grown in the absence of Etn compared to
      those grown in its presence, but the respective Kd values were almost the same.
      Furthermore, tyrosine phosphorylation of the EGF receptor was significantly lower
      in cells grown without Etn. Phosphatidylcholine (PC) synthesis in the liver is
      unique in that it occurs via stepwise methylation of PE. We found that without
      Etn supplementation, bezafibrate-induced inhibition of PE methylation increased
      the level of PE by decreasing its conversion to PC and stimulated DNA synthesis.
      Moreover, the function of EGF in stimulating DNA synthesis was significantly
      enhanced under Etn-sufficient conditions. These data suggest that Etn is a
      nutritional factor required for synthesis of adequate PE, levels of which are
      important for hepatocyte proliferation.

PMID- 16618208
TI  - Two lepidopteran cell lines stably transformed by the abc transporter gene pdr5
      show tolerance to diacetoxyscirpenol.
AB  - The pleiotropic drug resistance 5 gene (pdr5) encodes a multidrug membrane
      transporter and plays a very important role in the efflux of a broad range of
      chemicals in yeast cells. To study the possible function of pdr5 in insect cells,
      two stably pdr5-transformed lepidopteran insect cell lines, Sf21 and CF-203, were
      developed. Transcripts of pdr5 were detected in these two lines using Northern
      blotting and RT-PCR analysis. When cells were treated with the protein synthesis
      inhibitor diacetoxyscirpenol, the transformed Sf21 and CF-203 cell lines showed
      increased tolerance to this chemical. However, unlike in yeast cells, ecdysone
      agonist RH5992 could not be excluded by PDR5, probably because of low expression
      levels or imperfect incorporation of the recombinant protein in these transformed
      cell lines.

PMID- 16618209
TI  - Molecular analysis and characterization of PrEC, commercially available prostate
      epithelial cells.
AB  - Adenocarcinoma of the prostate comprises 95% of all prostate cancer. Commercially
      available primary cultures of "normal" prostate epithelial cells, PrECs, have
      been used as a convenient model to investigate neoplastic transformation. Here
      PrECs were characterized for the expression of lineage- and developmental
      specific markers cytokeratin (CK) 8 and 18, p63, chromogranin A, TMEPAI, S100P,
      NKX 3.1, ANKH, and FN 1 as well as androgen receptor and prostate-specific
      antigen by Western blot and Northern blot analyses, immunohistochemistry, reverse
      transcriptase-polymerase chain reaction (RT-PCR), and quantitative real-time PCR.
      Immunohistochemical staining detected PrECs positive in varying degrees for p63,
      CK 8, and CK 18, with only the rare cell being positive for chromogranin A. The
      PrECs also tested positive for p63 protein by Western blot analysis. RT-PCR with
      PrEC cDNA showed products for FN 1 and S100P but not for ANKH and androgen
      receptor or prostate-specific antigen. This profile of markers in PrEC cells is
      consistent with that expected for pubertal prostate epithelial cells.

PMID- 16618210
TI  - Osteopontin expression in coculture of differentiating rat fetal skeletal
      fibroblasts and myoblasts.
AB  - Skeletal fibroblasts in vitro can acquire myofibroblast phenotypes by the
      development of biochemical and morphological features, mainly the expression of
      alpha-smooth-muscle actin (alpha-SMA). Myogenic differentiation is a central
      event in skeletal muscle development, and has commonly been studied in vitro in
      the context of skeletal muscle development and regeneration. Controlling this
      process is a complex set of interactions between myoblasts and the extracellular
      matrix. Osteopontin (OPN) is an acidic, phosphorylated matrix protein that
      contains an Arg-Gly-Asp (RGD) cell attachment sequence and has been identified as
      an adhesive and migratory substrate for several cell types. The aim of this study
      was to investigate osteopontin expression during the differentiation of skeletal
      fibroblasts into myofibroblasts and during myogenesis in a coculture model.
      Fibroblasts and myoblasts were obtained from skeletal muscle of 18-d-old Wistar
      strain rat fetuses by enzymatic dissociation. At 1 and 9 d, cocultures were
      immunolabeled, and the cells were also separately subjected to Western blotting
      to analyze OPN expression. Our data using confocal microscopy showed that
      myoblasts displayed a strong staining for OPN and that this labeling was
      maintained after myotube differentiation. Conversely, during fibroblast
      differentiation into myofibroblasts, we observed a significant increase in OPN
      expression. The results obtained by immunolabeling were confirmed by Western
      blotting. We suggest that OPN is important mainly during early stages of
      myogenesis, facilitating myoblast fusion and differentiation, and that the
      increased expression of OPN in myofibroblasts might be related to its effects as
      a key cytokine regulating tissue repair and inflammation.

PMID- 16618211
TI  - Effects of hyaluronic acid in culture and cytochalasin B treatment before
      freezing on survival of cryopreserved bovine embryos produced in vitro.
AB  - One limitation to the widespread use of in vitro-produced embryos in cattle is
      their poor survival following cryopreservation. Two approaches for enhancing
      survival of in vitro-produced bovine embryos following cryopreservation were
      evaluated: culture in the presence of hyaluronic acid and alterations in the
      cytoskeleton through cytochalasin B treatment. The experiment was a 2 x 2
      factorial design to test main effects of hyaluronic acid added to culture at day
      5 after insemination (+ or -) and cryopreservation treatment (control or
      cytochalasin B). Embryos used for cryopreservation were blastocysts and expanded
      blastocysts harvested on day 7 after insemination. Cytochalasin B increased the
      percent of embryos that re-expanded (P < 0.0001) and that hatched following
      thawing (P < 0.05). The hatching percent was 29.6% for embryos treated with
      cytochalasin B versus 9.1% for control embryos. There was no significant effect
      of hyaluronic acid on survival although there was a tendency for embryos cultured
      with hyaluronic acid to have higher percent hatching if not treated with
      cytochalasin B (12.7% for hyaluronic acid versus 4.5% for control; hyaluronic
      acid x cytochalasin B interaction; P = 0.09). In conclusion, cytochalasin B
      treatment before freezing improved cryosurvival of bovine embryos produced in
      vitro. Such a treatment could be incorporated into methods for cryopreservation
      of bovine embryos provided post-transfer survival is adequate. In contrast,
      culture with hyaluronic acid was of minimal benefit- the increased cryosurvival
      in the absence of cytochalasin B was not sufficient to allow an adequate number
      of embryos to survive.

PMID- 16618212
TI  - Bacillus thuringiensis insecticidal Cry1ab toxin does not affect the membrane
      integrity of the mammalian intestinal epithelial cells: An in vitro study.
AB  - The mammalian intestinal epithelium has been found, based on in vivo experiments,
      to be resistant to insecticidal Cry toxins, which are derived from Bacillus
      thuringiensis and fatally damage insect midgut cells. Thus, the toxins are
      commonly used as a genetic resource in insect-resistant transgenic plants for
      feed. However, Cry toxins bind to the cellular brush border membrane vesicle
      (BBMV) of mammalian intestinal cells. In this study, we investigated the affinity
      of Cry1Ab toxin, a lepidopteran-specific Cry1-type toxin, to the cellular BBMV of
      two mammalian intestinal cells as well as the effect of the toxin on the membrane
      potential of three mammalian intestinal cells compared to its effects on the
      silkworm midgut cell. We found that Cry1Ab toxin did bind to the bovine and
      porcine BBMV, but far more weakly than it did to the silkworm midgut BBMV.
      Furthermore, although the silkworm midgut cells developed severe membrane
      potential changes within 1 h following the toxin treatment at a final
      concentration of 2 mug/ml, no such membraneous changes were observed on the
      bovine, porcine, and human intestinal cells. The present in vitro results suggest
      that, although Cry1Ab toxin may bind weakly or nonspecifically to certain BBMV
      components in the mammalian intestinal cell, it does not damage the cell's
      membrane integrity, thus exerting no subsequent adverse effects on the cell.

PMID- 16618213
TI  - Inter-species comparison of 7-hydroxycoumarin glucuronidation and sulfation in
      liver S9 fractions.
AB  - UDP glycosyltransferases (UGTs) and sulfotransferases (SULTs) are phase II
      enzymes that interact with a number of xenobiotics in humans and animals. Species
      differences in enzymatic characteristics have seldom been investigated. Liver S9
      fractions are commonly used for studying phase II metabolism in vitro. The
      objective of this study was to characterize the UGT and SULT activities in liver
      S9 fractions from various species including humans, monkeys, dogs, and rats. A
      single substrate, 7-hydroxycoumarin (7-HC), at several concentrations was
      incubated at 37 degrees C with the S9 reaction matrices along with necessary
      cofactors. The rate of formation of two metabolites, 7-HC-glucuronide (7-HC-G)
      and 7-HC-sulfate (7-HC-S), was determined with Liquid Chromatography/Tanderm Mass
      Spectrometry (LC/MS/MS). Apparent Km and Vmax values were calculated for each
      species. For the UGTs, the apparent Km and Vmax for 7-HC-G formation varied
      greatly among different species, with dog UGTs having both the highest Km and
      Vmax values. In contrast to UGTs, the Km for 7-HC-S formation showed no
      significant difference among humans, monkeys, and rats (approximately 3 microM).
      However, the Km in dog was 8.7 microM. Species differences with respect to phase
      II metabolism must be carefully considered when selecting an in vitro model
      system to study various aspects of drug metabolism.

PMID- 16618214
TI  - Mediated modeling of the impacts of enhanced UV-B radiation on ecosystem
      services.
AB  - This article describes the use of group model building to facilitate interaction
      with stakeholders, synthesize research results and assist in the development of
      hypotheses about climate change at the global level in relation to UV-B radiation
      and ecosystem service valuation. The objective was to provide a platform for
      integration of the various research components within a multidisciplinary
      research project as a basis for interaction with stakeholders with backgrounds in
      areas other than science. An integrated summary of the scientific findings, along
      with stakeholder input, was intended to produce a bridge between science and
      policymaking. We used a mediated modeling approach that was implemented as a
      pilot project in Ushuaia, Argentina. The investigation was divided into two
      participatory workshops: data gathering and model evaluation. Scientists and the
      local stakeholders supported the valuation of ecosystem services as a useful
      common denominator for integrating the various scientific results. The concept of
      economic impacts in aquatic and marsh systems was represented by values for
      ecosystem services altered by UV-B radiation. In addition, direct local
      socioeconomic impacts of enhanced UV-B radiation were modeled, using data from
      Ushuaia. We worked with 5 global latitudinal regions, focusing on net primary
      production and biomass for the marine system and on 3 plant species for the marsh
      system. Ecosystem service values were calculated for both sectors. The synthesis
      model reflects the conclusions from the literature and from experimental research
      at the global level. UV-B is not a significant stress for the marshes, relative
      to the potential impact of increases in the sea level. Enhanced UV-B favors
      microbial dynamics in marine systems that could cause a significant shift from
      primary producers to bacteria at the community level. In addition, synergetic
      effects of UV-B and certain pollutants potentiate the shift to heterotrophs. This
      may impact the oceanic carbon cycle by increasing the ratio of respiratory to
      photosynthetic organisms in surface waters and, thus, the role of the ocean as a
      carbon sink for atmospheric CO2. In summary, although changes in the marine
      sector due to anthropogenic influences may affect global climate change, marshes
      are expected to primarily be affected by climate change.

PMID- 16618216
TI  - Cats contract avian influenza virus.

PMID- 16618217
TI  - Questions definition of comparative medicine.

PMID- 16618218
TI  - The relationship between general practitioners and board-certified specialists in
      veterinary medicine.

PMID- 16618220
TI  - What is your diagnosis? Mass of hair on left side of the nasal choanae.

PMID- 16618219
TI  - What is your diagnosis? Rodenticide toxicosis.

PMID- 16618221
TI  - Congenital tarsal hyperextension in three cats.
AB  - CASE DESCRIPTION: 3 kittens were examined because of a malformation affecting the
      hind limbs, resulting in an inability to bear weight or ambulate normally.
      CLINICAL FINDINGS: 2 kittens were younger than 6 weeks of age, and 1 was 4 months
      of age at the time of initial examination. The congenital abnormality was
      characterized by severe tarsal hyperextension in which weight was borne on the
      cranial aspect of the tarsus, and the plantar surface of the metatarsus faced
      dorsally. In 2 kittens, the condition affected both hind limbs, and in the older
      kitten, the condition was unilateral. In the 2 kittens in which radiographs were
      obtained, no bone abnormalities were detected. Full-cylinder fiberglass casts
      were applied and changed weekly to accommodate growth. Owners administered
      physical therapy after final cast removal. TREATMENT AND OUTCOME: Conservative
      management involving external coaptation and physical therapy led to favorable
      results in all 3 cats. CLINICAL RELEVANCE: Although further studies are needed to
      determine the etiology of the disorder, affected kittens may be successfully
      treated with conservative management. Owners should be committed to the necessity
      for returning cats for serial cast changes, care for pressure sores, and
      administration of physical therapy after cast removal.

PMID- 16618223
TI  - Hemidiaphragmatic reconstruction with a transversus abdominis muscle flap after
      resection of a solitary diaphragmatic mesothelioma in a dog.
AB  - CASE DESCRIPTION: A 2-year-old Siberian Husky was evaluated because of a 2-week
      history of coughing and gagging and decreased appetite and activity level.
      CLINICAL FINDINGS: Radiography, surgery, and immunohistochemical examination
      revealed a solitary sclerosing mesothelioma extending from the left thoracic
      diaphragmatic surface that was adherent to the pericardium and the caudal
      mediastinum. TREATMENT AND OUTCOME: The tumor was resected along with most of the
      left hemidiaphragm, and the left transversus abdominis muscle was used to
      reconstruct the diaphragm. The 13th rib formed the base of the muscle flap. The
      muscle flap was transposed into the defect so that the mesothelium-lined surface
      faced the thoracic cavity and the deep aspect of the muscle formed the abdominal
      surface of the diaphragm. To minimize risk of adhesions, the exposed raw aspect
      of the abdominal surface was covered with porcine small intestinal submucosa.
      Recovery was uncomplicated, and the dog's appetite and activity level soon
      returned to normal. Evaluation 54 days after surgery revealed 2 subcutaneous
      masses on the thorax and masses in the liver and both kidneys; histologic and
      immunohistochemical analyses revealed metastasis of the original tumor. The dog
      was euthanatized. CLINICAL RELEVANCE: Hemidiaphragmatic reconstruction with a
      transversus abdominis muscle flap after resection of a diaphragmatic tumor was
      successful. The muscle flap was easily harvested and transposed into the
      diaphragmatic defect.

PMID- 16618224
TI  - Choledochal tube stenting for decompression of the extrahepatic portion of the
      biliary tract in dogs: 13 cases (2002-2005).
AB  - OBJECTIVE: To determine clinicopathologic features, surgical management,
      complications, and long-term outcome associated with diseases of the extrahepatic
      portion of the biliary tract treated via choledochal stent placement in dogs.
      DESIGN: Retrospective case series. ANIMALS: 13 dogs. PROCEDURE: Data were
      obtained from medical records, and follow-up information was obtained via
      reexamination or telephone interview with owners or referring veterinarians.
      RESULTS: 10 dogs had extrahepatic biliary obstruction (EHBO), 6 as a result of
      pancreatitis. Two dogs had rupture of the common bile duct associated with
      cholelithiasis. In 1 dog, a stent was placed prophylactically after
      gastroduodenostomy was performed for a perforated duodenal ulcer. Nine of 13 dogs
      survived the perioperative period and were discharged. No recurrence of EHBO or
      other complications developed in the discharged dogs while the stents were in
      place. Median follow-up period from surgery to last owner contact was 13.3
      months. In 1 dog, the stent was removed endoscopically 10 months after surgery
      and EHBO recurred 9 months after stent removal because of cholangitis. In 4 of 5
      dogs that were discharged from the hospital, in which the fate of the stent could
      be confirmed and the stent was secured to the duodenal wall with absorbable
      suture materials, the stents were passed in the feces 1 to 11 months after
      surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Choledochal tube stenting is an
      effective method of decompression of the extrahepatic portion of the biliary
      tract in dogs and provides a less complex alternative to traditional
      cholecystoenterostomy techniques in select cases.

PMID- 16618225
TI  - Postoperative results of unilateral arytenoid lateralization for treatment of
      idiopathic laryngeal paralysis in dogs: 39 cases (1996-2002).
AB  - OBJECTIVE: To evaluate postoperative results for dogs with idiopathic laryngeal
      paralysis that underwent unilateral arytenoid lateralization (UAL). DESIGN:
      Retrospective case series. ANIMALS: 39 dogs with idiopathic laryngeal paralysis.
      PROCEDURE: Medical records were reviewed, and information on surgical technique,
      hospitalization time, postoperative treatment, and complications was obtained.
      Owners were contacted by telephone for additional information if necessary.
      RESULTS: In all dogs, UAL had been performed by a single surgeon who used a
      standard surgical technique. Long-term follow-up information was available for
      all 39 dogs; mean follow-up time was 29.6 months (range, 3 to 61 months). Seven
      (18%) dogs developed postoperative pneumonia, and 6 of the 7 recovered with
      treatment. Twenty-two of the 39 (56%) dogs had minor complications, including
      unresolved coughing or gagging, continued exercise intolerance, vomiting, and
      seroma formation. Owners of 35 of the 39 (90%) dogs reported an improvement in
      postoperative quality-of-life score. Median survival time was 12 months; only 1
      dog was euthanized because of respiratory tract disease following surgery.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that UAL will improve quality
      of life in most dogs with idiopathic laryngeal paralysis. However, the
      complication rate is high, with postoperative pneumonia being the most important
      major complication. Minor complications were common but did not adversely affect
      owner-assigned quality-of-life scores in most dogs.

PMID- 16618226
TI  - Evaluation of total intravenous anesthesia with propofol or ketamine-medetomidine
      propofol combination in horses.
AB  - Objective-To compare the anesthetic and cardiorespiratory effects of total IV
      anesthesia with propofol (P-TIVA) or a ketamine-medetomidine-propofol combination
      (KMP-TIVA) in horses. Design-Randomized experimental trial. Animals-12 horses.
      Procedure-Horses received medetomidine (0.005 mg/kg [0.002 mg/lb], IV).
      Anesthesia was induced with midazolam (0.04 mg/kg [0.018 mg/lb], IV) and ketamine
      (2.5 mg/kg [1.14 mg/lb], IV). All horses received a loading dose of propofol (0.5
      mg/kg [0.23 mg/lb], IV), and 6 horses underwent P-TIVA (propofol infusion). Six
      horses underwent KMP-TIVA (ketamine [1 mg/kg/h {0.45 mg/lb/h}] and medetomidine
      [0.00125 mg/kg/h {0.0006 mg/lb/h}] infusion; the rate of propofol infusion was
      adjusted to maintain anesthesia). Arterial blood pressure and heart rate were
      monitored. Qualities of anesthetic induction, transition to TIVA, and maintenance
      of and recovery from anesthesia were evaluated. Results-Administration of KMP IV
      provided satisfactory anesthesia in horses. Compared with the P-TIVA group, the
      propofol infusion rate was significantly less in horses undergoing KMP-TIVA (0.14
      +/- 0.02 mg/kg/min [0.064 +/- 0.009 mg/lb/min] vs 0.22 +/- 0.03 mg/kg/min [0.1 +/
      0.014 mg/lb/min]). In the KMP-TIVA and P-TIVA groups, anesthesia time was 115 +/
      17 minutes and 112 +/- 11 minutes, respectively, and heart rate and arterial
      blood pressure were maintained within acceptable limits. There was no significant
      difference in time to standing after cessation of anesthesia between groups.
      Recovery from KMP-TIVA and P-TIVA was considered good and satisfactory,
      respectively. Conclusions and Clinical Relevance-In horses, KMP-TIVA and P-TIVA
      provided clinically useful anesthesia; the ketamine-medetomidine infusion
      provided a sparing effect on propofol requirement for maintaining anesthesia.

PMID- 16618227
TI  - Management of hydrops amnion in a mare resulting in birth of a live foal.
AB  - CASE DESCRIPTION: A 19-year-old Thoroughbred mare was evaluated at 265 days of
      gestation with a markedly distended abdomen and edema of the ventral portion of
      the abdomen. CLINICAL FINDINGS: The uterus was distended over the pelvic rim,
      making transrectal palpation of the fetus impossible. Transabdominal
      ultrasonography revealed excessive amounts of fetal fluid. Results of analysis of
      fluid obtained via amnio- and allantocentesis confirmed that the amniotic cavity
      was large. TREATMENT AND OUTCOME: The mare was monitored for signs of weakness of
      the prepubic tendon and abdominal wall. The fetus and placenta were monitored for
      signs of stress and pending abortion. Flunixin meglumine and altrenogest were
      administered to the mare. Parturition was attended and occurred at 321 days'
      gestation. Postpartum complications in the mare included hypovolemic shock and
      cardiac arrhythmias. Both conditions were treated, and the mare recovered. The
      foal was considered small, had bilateral angular limb deformities, and was unable
      to nurse. The foal was given plasma for failure of passive transfer of immunity.
      Ten months later, the foal underwent procedures to correct limb deformities.
      CONCLUSIONS AND CLINICAL RELEVANCE: Hydrops conditions are rare in horses, with
      hydrops allantois occurring more frequently than hydrops amnion; reportedly
      result in fetal or neonatal death; and may result in death of or injury to the
      mare. Close monitoring of maternal and fetal health in combination with
      supportive treatment of the mare can result in the safe progression of a hydrops
      pregnancy and the birth of a live foal.

PMID- 16618229
TI  - Nocardioform placentitis with isolation of Amycolatopsis spp in a Florida-bred
      mare.
AB  - CASE DESCRIPTION: A 4-year-old Thoroughbred mare was evaluated because of
      placental abnormalities and a retained placental remnant. CLINICAL FINDINGS:
      Microbial culture of the placenta yielded pure growth of Amycolatopsis spp.
      Histologic examination of the placenta revealed a focally expanding chorionitis
      with intralesional gram-positive filamentous bacilli and multifocal allantoic
      adenomatous hyperplasia on the apposing allantoic surface. TREATMENT AND OUTCOME:
      Treatment with lavage and oxytocin resulted in expulsion of the placental remnant
      within hours of parturition. The mare did not become pregnant again despite
      multiple breedings. The foal appeared healthy but died of complications during an
      elective surgical procedure at 7 weeks of age. CONCLUSIONS AND CLINICAL
      RELEVANCE: To the author's knowledge, all previously confirmed cases of
      nocardioform placentitis have been in mares bred in the central Kentucky region.
      Indications that the pathogen in the mare reported here is a different species
      than that isolated in Kentucky suggest that this is an emerging disease. Mares
      with nocardioform placentitis usually do not have the same clinical signs as
      mares with placentitis resulting from an ascending pathogen.

PMID- 16618230
TI  - Presumptive fenbendazole toxicosis in North American porcupines.
AB  - CASE DESCRIPTION: 4 North American porcupines were evaluated because of diarrhea
      or neutropenia (or both) that developed after treatment with fenbendazole for
      intestinal parasites. CLINICAL FINDINGS: Complete blood cell count abnormalities
      included severe neutropenia in all affected porcupines and mild anemia in some of
      them. In 2 porcupines, postmortem findings included bone marrow hypoplasia and
      intestinal crypt cell necrosis. TREATMENT AND OUTCOME: Affected porcupines
      received supportive care including fluid supplementation and broad-spectrum
      antimicrobials. The 2 surviving animals recovered after 9 to 33 days of
      treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Fenbendazole is an anthelminthic
      that may be used in an extralabel manner for the treatment of intestinal
      parasitism in wildlife species. The drug inhibits mitosis and can affect rapidly
      dividing cell lines, such as those in the bone marrow and intestinal crypt
      mucosa. Fenbendazole may not be an appropriate anthelminthic choice in North
      American porcupines.

PMID- 16618231
TI  - Guidelines for the management of acute coronary syndromes 2006.

PMID- 16618233
TI  - Staphylococcus aureus: a guide for the perplexed.
AB  - The differences between community-acquired and health care-associated MRSA
      explained.

PMID- 16618232
TI  - Preventing falls among elderly people in the hospital environment.
AB  - Falls and related injuries among seniors are a compelling ongoing priority for
      Australian health research.

PMID- 16618234
TI  - What do we know about perioperative ischaemic cardiac events in patients
      undergoing non-cardiac surgery?
AB  - A recent review shows how much more we need to find out about this important
      problem.

PMID- 16618235
TI  - Sustained reduction in serious fall-related injuries in older people in hospital.
AB  - OBJECTIVE: To determine whether the rate of falls and associated serious injuries
      in a hospital aged care setting can be reduced using a multistrategy prevention
      approach. DESIGN, SETTING AND PARTICIPANTS: Three-year quality improvement
      project comparing data at baseline (2001) and at 2-year follow-up (2003) after
      interventions to reduce falls. All patients admitted to the Aged Care Services
      wards at Caulfield General Medical Centre, Melbourne, between January 2001 and
      December 2003 were included. INTERVENTIONS: Multistrategy approach phased in over
      3 months from September 2001 and involving data gathering, risk screening with
      appropriate interventions, work practice changes, environmental and equipment
      changes, and staff education. MAIN OUTCOME MEASURES: Total number of falls;
      number of falls resulting in serious injuries (fractures, head injuries, death);
      staff compliance with the risk assessment. RESULTS: Over a 2-year period, there
      was a 19% reduction in the number of falls per 1000 occupied bed-days (OBDs)
      (12.5 v 10.1; P = 0.001) and a 77% reduction in the number of falls resulting in
      serious injuries per 1000 OBDs (0.73 v 0.17; P < 0.001). Staff compliance with
      completing the falls risk assessment tool increased from 42% to 70%, and 60% of
      staff indicated they had changed their work practices to prevent falls.
      CONCLUSION: A multistrategy falls prevention program in an aged care hospital
      setting produced a significant reduction in the number of falls and a marked
      reduction in serious fall-related injuries. Incorporating a falls prevention
      program into all levels of an organisation, as part of daily care, is crucial to
      the success and sustainability of falls prevention.

PMID- 16618236
TI  - Methicillin-resistant Staphylococcus aureus in the Australian community: an
      evolving epidemic.
AB  - OBJECTIVE: To describe antimicrobial resistance and molecular epidemiology of
      methicillin-resistant Staphylococcus aureus (MRSA) isolated in community settings
      in Australia. DESIGN AND SETTING: Survey of S. aureus isolates collected
      prospectively Australia-wide between July 2004 and February 2005; results were
      compared with those of similar surveys conducted in 2000 and 2002. MAIN OUTCOME
      MEASURES: Up to 100 consecutive, unique clinical isolates of S. aureus from
      outpatient settings were collected at each of 22 teaching hospital and five
      private laboratories from cities in all Australian states and territories. They
      were characterised by antimicrobial susceptibilities (by agar dilution methods),
      coagulase gene typing, pulsed-field gel electrophoresis, multilocus sequence
      typing, SCCmec typing and polymerase chain reaction tests for Panton-Valentine
      leukocidin (PVL) gene. RESULTS: 2652 S. aureus isolates were collected, of which
      395 (14.9%) were MRSA. The number of community-associated MRSA (CA-MRSA) isolates
      rose from 4.7% (118/2498) of S. aureus isolates in 2000 to 7.3% (194/2652) in
      2004 (P = 0.001). Of the three major CA-MRSA strains, WA-1 constituted 45/257
      (18%) of MRSA in 2000 and 64/395 (16%) in 2004 (P = 0.89), while the Queensland
      (QLD) strain increased from 13/257 (5%) to 58/395 (15%) (P = 0.0004), and the
      south-west Pacific (SWP) strain decreased from 33/257 (13%) to 26/395 (7%) (P =
      0.01). PVL genes were detected in 90/195 (46%) of CA-MRSA strains, including 5/64
      (8%) of WA-1, 56/58 (97%) of QLD, and 25/26 (96%) of SWP strains. Among health
      care-associated MRSA strains, all AUS-2 and AUS-3 isolates were multidrug
      resistant, and UK EMRSA-15 isolates were resistant to ciprofloxacin and
      erythromycin (50%) or to ciprofloxacin alone (44%). Almost all (98%) of CA-MRSA
      strains were non-multiresistant. CONCLUSIONS: Community-onset MRSA continues to
      spread throughout Australia. The hypervirulence determinant PVL is often found in
      two of the most common CA-MRSA strains. The rapid changes in prevalence emphasise
      the importance of ongoing surveillance.

PMID- 16618238
TI  - High-cost users of hospital beds in Western Australia: a population-based record
      linkage study.
AB  - OBJECTIVE: To describe how high-cost users of inpatient care in Western Australia
      differ from other users in age, health problems and resource use. DESIGN AND DATA
      SOURCES: Secondary analysis of hospital data and linked mortality data from the
      WA Data Linkage System for 2002, with cost data from the National Hospital Cost
      Data Collection (2001-02 financial year). OUTCOME MEASURES: Comparison of high
      cost users and other users of inpatient care in terms of age, health profile
      (major diagnostic category) and resource use (annualised costs, separations and
      bed days). RESULTS: Older high-cost users (> or = 65 years) were not more
      expensive to treat than younger high-cost users (at the patient level), but were
      costlier as a group overall because of their disproportionate representation (n =
      8466; 55.9%). Chronic stable and unstable conditions were a key feature of high
      cost users, and included end stage renal disease, angina, depression and
      secondary malignant neoplasms. High-cost users accounted for 38% of both
      inpatient costs and inpatient days, and 26% of inpatient separations. CONCLUSION:
      Ageing of the population is associated with an increase in the proportion of high
      cost users of inpatient care. High costs appear to be needs-driven. Constraining
      high-cost inpatient use requires more focus on preventing the onset and
      progression of chronic disease, and reducing surgical complications and injuries
      in vulnerable groups.

PMID- 16618237
TI  - Impact of an education campaign on management in pregnancy of women infected with
      a blood-borne virus.
AB  - OBJECTIVE: To assess obstetricians' antenatal screening practice for blood-borne
      viruses (HIV, hepatitis B and C viruses [HBV and HCV]) and knowledge about
      management during labour and risk of transmission via breastfeeding for infected
      women after an educational intervention, Australia. DESIGN: Cohort study, with
      surveys before and after an educational intervention. SETTING AND PARTICIPANTS:
      Survey 1 was mailed in 2002-2003 to all 767 Fellows registered with the Royal
      Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG),
      and Survey 2 was mailed in 2004 to the 743 of these Fellows who were still
      practising. INTERVENTION: Multifaceted intervention with mail-out of survey
      results and a summary of recommended management, publication of two review
      articles in the RANZCOG journal, and an oral presentation at the RANZCOG annual
      scientific meeting. MAIN OUTCOME MEASURES: Self-reported frequency of antenatal
      screening for blood-borne viruses, change in practice based on a woman's
      infection status, and advice given about risk of virus transmission via
      breastfeeding in Survey 2, compared with Survey 1. RESULTS: Survey 2 (response
      rate, 68%) found increases from the previous survey in the proportion of
      respondents reporting they always offered antenatal screening for HIV, from 51%
      to 59%, and for HCV, from 60% to 69% (P = 0.001 for both). For women with HIV
      infection, the proportion of respondents always recommending elective caesarean
      section increased from 37% to 49% (P = 0.001) and always avoiding rupture of
      membranes increased from 33% to 49% (P < 0.001). The proportion who reported
      advising (incorrectly) that breastfeeding is associated with increased risk of
      transmission to the infant decreased from 34% to 25% for HBV (P = 0.01) and from
      47% to 39% for HCV (P = 0.03). CONCLUSION: The frequency of antenatal testing for
      HIV and HCV is increasing in Australia. Knowledge about interventions to reduce
      mother-to-child transmission of HIV and knowledge of the risk of HBV and HCV
      transmission via breastfeeding improved after a relatively simple educational
      intervention.

PMID- 16618239
TI  - Cough in children: definitions and clinical evaluation.
AB  - The aetiology and management approach for cough in children differs greatly to
      that in adults, so the empirical approach commonly used in adults is unsuitable
      for children. Clinical evaluation of cough in children should include an
      assessment of environmental factors, particularly tobacco smoke, parental
      concerns and expectations. Most children with acute cough are likely to have an
      uncomplicated viral acute respiratory tract infection, but the possibility of a
      more serious problem, especially aspiration of foreign material, should always be
      considered. Isolated chronic cough in children is rarely asthma, and the term
      "cough variant asthma" should not be used. Over-the-counter and prescription
      medications are ineffective for the symptomatic relief of acute cough. Treatment
      for chronic cough should be based on aetiology. Because of the favourable natural
      history of cough, a "positive" response in medication trials should not be
      assumed to be due to the medication. Children should be reassessed within the
      expected timeframe of response to therapy.

PMID- 16618241
TI  - No longer a biological waste product: umbilical cord blood.
AB  - Haematopoietic stem cell transplantation is an accepted curative therapy for many
      cancers and inherited non-malignant diseases, including bone marrow failure
      syndromes, haemoglobinopathies, and inborn errors of metabolism. Stem cells can
      be used from the bone marrow or blood of matched siblings or appropriately
      matched unrelated volunteers, but many patients do not have a suitably matched
      donor. Umbilical cord blood (UCB) has been successfully used as an alternative
      stem cell source. It has the advantage of tolerance for a degree of human
      leukocyte antigen (HLA) incompatibility not possible with adult bone marrow,
      resulting in greater likelihood of finding an appropriate match. UCB is also
      stored fully tested and cryopreserved, leading to rapid availability. Greatest
      clinical experience in UCB transplants has been in treating paediatric leukaemia.
      Results using well matched UCB grafts are equivalent or better than with
      unrelated bone marrow transplant. Cell dose and the degree of HLA matching are
      critical determinants in the success of UCB transplant. The use of UCB in older
      children and adult patients has been limited by the fixed, low cell dose
      available in a UCB unit, relative to recipient weight. This can be overcome by
      strategies such as using two or more UCB units. Early animal studies suggest that
      UCB may have the potential to differentiate into other cell types, including
      nervous tissue, and may in future play a role in the treatment of disorders such
      as Alzheimer disease and Parkinson disease.

PMID- 16618240
TI  - Health care-associated Staphylococcus aureus bloodstream infections: a clinical
      quality indicator for all hospitals.
AB  - Staphylococcus aureus bloodstream (SAB) infections are common and serious causes
      of morbidity and mortality that incur considerable health care costs and are
      potentially preventable, Australia. It should be relatively easy for hospitals to
      collect data on the incidence of SAB episodes, to determine whether infections
      were acquired in hospital or in the community, and to establish whether they were
      health care associated. The proportion of SAB infections caused by methicillin
      resistant S. aureus strains should be a useful indicator of the level of control
      of antibiotic resistance in the community and in the health care setting.
      Continuous monitoring of infection incidence would enable health care facilities
      to determine the effectiveness of interventions designed to minimise SAB
      infections.

PMID- 16618242
TI  - Accessing health outcome data on high-cost medicines in Australia.
AB  - Data on health outcomes resulting from the use of medicines provide important
      evidence of cost-effectiveness. Currently, clinical information on individual
      patients, collected by Medicare Australia to assess eligibility for subsidised
      treatment with high-cost medicines, is inaccessible for research. Comprehensive
      data on drug use and health outcomes should be made accessible, with appropriate
      regulation, so that the effectiveness, utility and appropriateness of our systems
      of access to medicines can be independently analysed. In the interests of
      continuous improvement in medical care and optimal use of limited resources, we
      strongly advocate the enhancement of Medicare Australia databases and
      liberalisation of arrangements for access to administrative and clinical data.

PMID- 16618244
TI  - Thoracic splenosis: a treatment approach.

PMID- 16618243
TI  - Teaching on the run tips 13: being a good supervisor--preventing problems.

PMID- 16618245
TI  - High rate of immediate systemic hypersensitivity reactions to tiger snake
      antivenom.

PMID- 16618247
TI  - Invasive meningococcal disease presenting with cellulitis.

PMID- 16618246
TI  - An African strain of community methicillin-resistant Staphylococcus aureus in a
      Burundi refugee.

PMID- 16618248
TI  - Professional development of registrars.

PMID- 16618249
TI  - Chronic heart failure: time to optimise methods of diagnosis in the community.

PMID- 16618250
TI  - Effective shade structures.

PMID- 16618256
TI  - Clinical characteristics of tension-type headache and migraine in adolescents: a
      student-based study.
AB  - BACKGROUND AND OBJECTIVES: Adolescent headaches, particularly migraine, might
      present with different features from adult headaches. The objectives of this
      study were to investigate the characteristics of tension-type headache and
      migraine, to find the sensitivity and specificity of the diagnostic criteria of
      the IHS classification according to age and gender. METHODS: A multistep,
      stratified, cluster sampling method was used for subject selection. The estimated
      sample size was 2387. The study was conducted in two phases: the questionnaire
      and the face to face interview phases. During the semistructured interview, a
      clinical diagnosis has been made and clinical characteristics have been recorded.
      RESULTS: All headaches fulfilled the criteria of duration. The most common
      feature of migraine was moderate to severe (92.4%), pulsating pain (79.2%). For
      ETTH, bilateral localization (91.3%) and mild to moderate pain intensity (90.6%)
      were the most common features. Younger adolescents showed mixed headache
      characteristics. Highest sensitivities for migraine were duration (100%),
      moderate to severe pain (92.4%), and pulsating quality of pain (79.2%). Vomiting,
      trigger factors food and alcohol had a high specificity for migraine.
      CONCLUSIONS: Our data strongly support continuum hypothesis. In early adolescence
      headaches might present with mixed headache characteristics. Age and gender have
      some influence on headache characteristics, particularly on migraine. The
      sensitivity and specificity of case definition criteria of ICHD-2 for adolescent
      migraine is moderate and need to be reconsidered.

PMID- 16618254
TI  - Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis
      -part 2.
AB  - Migraine headache is strongly influenced by reproductive events that occur
      throughout the lifespan of women. Each of these reproductive events has a
      different "hormonal milieu," which might modulate the clinical course of migraine
      headache. Estrogen and progesterone can be preventative or provocative for
      migraine headache under different circumstances depending on their absolute serum
      levels, constancy of exposure, and types of estrogen/progesterone derivatives.
      Attacks of migraine with and without aura respond differently to changes in
      ovarian hormones. Clearly a greater knowledge of ovarian hormones and their
      effect on migraine is essential to a greater understanding of the mechanisms and
      pathogenesis of migraine headache.

PMID- 16618257
TI  - Relationship between migraine and epilepsy in pediatric age.
AB  - OBJECTIVE: Many studies have supported the hypothesis of alteration of cortical
      hyperexcitability as a possible pathological mechanism underlying the onset of
      migraine and epileptic attacks. Different biochemical pathways involving cellular
      structures may increase or decrease the excitability of neuronal membranes. The
      aim of this study was to identify a possible link between migraine and epilepsy
      from a clinical and neurophysiologic point of view. METHODS: One-hundred thirty
      seven children and adolescents consecutively diagnosed for tension-type headache
      and idiopathic migraine with and without aura were studied. Anamnestic, clinical,
      and instrumental data were collected by a neurological examination, a specific
      questionnaire, and awake electroencephalogram (EEG) registrations. EEG features
      of nonheadache and nonseizures control group were compared. RESULTS: Fourteen
      cases (10.2%) had a positive history for seizures with fever, isolated seizures,
      or epilepsy. Distribution differed according to headache diagnosis; migraine with
      aura (MWA) was largely prevalent. Specific electroencephalographic abnormalities
      were present in 11.7% of the sample, with a significant different distribution
      across the groups of children with headache and the control group: specific
      interictal abnormalities were found in 10 of 23 (43.5%) children with MWA. Two
      factors, seizures and specific interictal electroencephalographic abnormalities,
      showed a different distribution in patients with MWA compared to other classes of
      headache and control group (P < or = .01). CONCLUSION: The present study supports
      the hypothesis of a possible clinical continuum between some types of MWA and
      epileptic syndromes as entities due to altered neuronal excitability with similar
      genetic substrates.

PMID- 16618255
TI  - "Benign" imaging abnormalities in children and adolescents with headache.
AB  - OBJECTIVE: To study the frequency of "benign" abnormalities on brain imaging in
      children with headache, compare it with the frequency of imaging findings that
      dictate a change in patient management, and determine the association of benign
      findings with headache. METHODS: A database of 681 headache patients from the
      pediatric outpatient neurology department over 2 years was reviewed. Patients
      with benign imaging abnormalities were compared to those with nonbenign findings.
      Benign abnormalities were defined as those that did not result in a change in
      patient management. Using literature review, we discuss the benign findings and
      their possible association with headache. RESULTS: Two-hundred and forty-one
      patients (35.4%) had imaging at our facility. Two-hundred and eighteen had brain
      magnetic resonance imaging and 23 had brain computed tomography (CT) only. Twenty
      two patients had CT of the sinuses in addition to brain imaging. Forty-six
      (19.1%) were found to have 50 benign abnormalities including 13 sinus disease, 11
      Chiari I malformations, 7 nonspecific white matter abnormalities, 5 venous
      angiomas, 5 arachnoid cysts, 4 enlarged Virchow-Robin spaces, 2 pineal cysts, 1
      mega cisterna magna, 1 fenestration of the proximal basilar artery, and 1
      periventricular leukomalacia. Twenty-three patients (9.5%) had findings requiring
      a change in management. These included 5 sinus disease, 4 tumors, 4 old infarcts,
      3 Chiari I, 2 moyamoya, 1 intracranial vascular stenosis, 1 internal jugular vein
      occlusion, 1 arteriovenous malformation, 1 demyelinating disease, and 1
      intracerebral hemorrhage. When excluding sinusitis, which was evident clinically
      prior to imaging, 3 patients had absence of abnormal neurologic symptoms and
      signs and imaging findings that resulted in a change in management. CONCLUSIONS:
      Approximately 20% of pediatric headache patients with brain imaging have benign
      abnormalities that do not result in a change in headache management. Imaging
      findings that require a change in management are rare in patients with an absence
      of abnormal neurologic symptoms and signs, occurring in 1.2% of patients imaged
      in this study.

PMID- 16618258
TI  - Migraine is associated with menorrhagia and endometriosis.
AB  - OBJECTIVE: To evaluate the frequency of menorrhagia and endometriosis in female
      migraineurs compared to age-matched women without headache. BACKGROUND: Migraine
      predominantly affects women of childbearing age and is often associated with the
      menstrual period, yet there is a paucity of data regarding the relationship of
      migraine and menstrual disorders. METHODS: Women diagnosed with migraine, using
      International Headache Society criteria and an age- and sex-matched control
      group, were administered a semistructured questionnaire regarding migraine and
      migraine-related disability, menstrual history, other bleeding history, vascular
      event history, and vascular risk factors. RESULTS: Fifty female migraineurs
      between the ages of 22 and 50 years and 52 age-matched women (mean age 37 years)
      were enrolled in the study. Similar proportions of women in each group reported
      using hormone contraceptives (30% vs. 33%, P = .77) and hormone replacement
      therapy (12% vs. 8%, P = .69). The proportions presently menstruating (64 % vs.
      80%, P = .20) and status after hysterectomy were similar (24% vs. 14%, P = .84).
      Menorrhagia (defined as at least three consecutive heavy periods), both current
      and prior, was more commonly reported in migraineurs (63% vs. 37%, P = .009),
      with higher likelihood of staining clothes by menses (35% vs. 8%, P = .003), and
      significant impact of menses on activities of daily living (on a 10-point Likert
      scale) with work/school participation (P = .02), family activities (P < .0001),
      sleep (P = .003), life enjoyment (P = .001), mood (P = .02), and overall quality
      of life (P = .003). Endometriosis, which may be associated with menorrhagia, was
      also more commonly diagnosed in the migraineurs (30% vs. 4%, P = .001). The
      migraineurs more frequently described bruising (40% vs. 10%, P < .001) and rectal
      bleeding (18% vs. 2%, P = .017) but not more serious bleeding problems.
      Nonsteroidal anti-inflammatory drug (NSAID) use was more frequent in the migraine
      group (28% vs. 12%, P = .036), and significance for increased menorrhagia,
      endometriosis, menstrual interference, and bruising was maintained, even when
      controlling for the use of NSAIDs. With logistic regression, menorrhagia was
      significantly associated with migraine, adjusted odds ratio (OR) = 2.8 (95% CI
      1.2 to 6.5), and with endometriosis, adjusted OR = 10.5 (95% CI 2.2 to 51.4).
      There were no differences in vascular events and risk factors, except for trends
      of increased hypertension (25% vs. 10%, P = .05), transient ischemic
      attack/stroke (10% vs. 2%, P = .08), and Raynaud's disease (10% vs. 2%, P = .08)
      in the migraineurs. CONCLUSION: Women with migraine have a higher frequency of
      menorrhagia, endometriosis, and associated psychosocial consequences. These
      findings suggest that there should be further study of factors influencing
      endometriosis and menstrual blood flow, such as eicosanoids and platelet
      function, in migraineurs.

PMID- 16618259
TI  - The role of cardiac and pulmonary pathology in migraine: a hypothesis.
AB  - From observation of recent data linking migraine with right-to-left shunts and by
      analogy with the etiologies of decompression illness, we postulate that cardiac
      and pulmonary pathology can have an important effect on the cranial final common
      pathway that generates attacks of migraine. One possible mechanism is associated
      with a significant right-to-left shunt, which is usually through a persistent
      foramen ovale, but is sometime through a pulmonary shunt. This allows a venous
      agent, possibly 5-hydroxytryptamine, to bypass the lung filter. Migraine can
      occur when there is no shunt if similar agents are liberated in the left heart
      beyond the lung filter, possibly by platelet activation. Migraine could also
      occur if the venous agents are produced in such large amounts that they overwhelm
      the pulmonary filter or are unaffected by passage through the lungs. In some
      individuals migraine may be unrelated to blood-borne triggers.

PMID- 16618260
TI  - Patent foramen ovale and migraine: why the flap?

PMID- 16618261
TI  - Migraines linked to intrapulmonary right-to-left shunt.
AB  - OBJECTIVE: To determine if there is an association between migraines and
      intrapulmonary right-to-left shunt. BACKGROUND: Several studies have described an
      association between migraines and intracardiac right-to-left shunt. METHODS:
      Patients with hereditary hemorrhagic telangiectasia (HHT) were retrospectively
      recruited from the Toronto Hereditary Hemorrhagic Telangiectasia Center Clinical
      Database. All patients had been prospectively, systematically asked about a
      history of migraines and systematically screened for pulmonary and cerebral
      arteriovenous malformations (AVMs). All patients with a definite diagnosis of
      HHT, assessed during a 2-year period (February 1997 to April 1999), were
      included. Univariate analyses and logistic regression were performed, for
      migraine as the dependent variable and the following independent variables: age,
      sex, pulmonary AVMs, and cerebral AVMs. RESULTS: Of the 200 patients assessed
      during the 2-year period, 124 (62%) had a definite diagnosis of HHT and were
      included in the analysis. Eighty (65%) were females. Forty-seven (38%) of the HHT
      patients had a history of migraine, of whom 38 (81%) had migraine with aura. The
      prevalence of migraine was greater in patients with pulmonary AVMs (46%) compared
      to patients without pulmonary AVMs (33%), OR = 1.7 (0.8 to 3.6), though this did
      not reach statistical significance (P = .14). Pulmonary AVMs were significantly
      associated with migraine (OR = 2.4, 95% CI = 1.1 to 5.5, P = .04), after
      adjustment for age and sex, using logistic regression. CONCLUSIONS: There is a
      significant association between intrapulmonary right-to-left shunt and migraine.

PMID- 16618265
TI  - The impact of migraine on patients with major depressive disorder.
AB  - BACKGROUND: The impact of migraine and other headache types among psychiatric
      outpatients with major depressive disorder (MDD) has not been fully described.
      OBJECTIVE: To investigate the impact of migraine on the severity, physical, and
      anxiety symptoms in patients with MDD and to examine the interaction between
      headache and depression. METHODS: This clinic-based study enrolled consecutive
      psychiatric outpatients meeting DSM-IV criteria for MDD. Headache types were
      diagnosed based on the International Classification of Headache Disorders, 2nd
      edition (2004). Three psychometric instruments were used to evaluate anxiety,
      depression, and physical components: the Hamilton Depression Rating Scale, the
      Beck Depression Inventory, and the Hospital Anxiety and Depression Scale. In
      addition, the interactions between headache and their depressive episode were
      also evaluated. RESULTS: Compared with patients without migraine, MDD patients
      with comorbid migraine (n = 73, 48.3%) had higher physical and anxiety scores on
      the three psychometric instruments. Migraine accounted for 5% to 11% of the
      variance of the total scores on the three psychometric scales. Approximately half
      (48.5%) of patients reported headache worsening during or after a depressive
      episode. CONCLUSIONS: Our study found that comorbidity of migraine in patients
      with MDD was associated with more anxiety and physical symptoms. Headache should
      not be considered as only a somatic symptom of depression, but should be treated
      as an important comorbid disorder because it might exacerbate or interact with
      depression during a depressive episode.

PMID- 16618262
TI  - Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute
      migraine: results from a multicenter, double-blind, randomized, parallel-group,
      single-dose, placebo-controlled study.
AB  - OBJECTIVE: Compare the effectiveness of a combination analgesic containing
      acetaminophen, aspirin, and caffeine to that of ibuprofen in the treatment of
      migraine. METHODS: Multicenter, double-blind, randomized, parallel-group, placebo
      controlled, single-dose study. A total of 1555 migraineurs were included in the
      analysis. No patients were excluded solely because of severity of symptoms or
      degree of disability. A single 2-tablet dose for each of the 3 treatment groups:
      a combination product containing acetaminophen 250 mg, aspirin 250 mg, and
      caffeine 65 mg per tablet (AAC); ibuprofen 200 mg per tablet (IB); or matching
      placebo. The primary efficacy endpoint was the weighted sum of pain relief (PAR)
      scores at 2 hours postdose (TOTPAR2) and an important secondary endpoint was the
      time to onset of meaningful relief. RESULTS: There were 669 patients in the AAC
      group, 666 patients in the IB group, and 220 patients in the placebo group. The 3
      treatment groups had similar demographic profiles, migraine histories, and
      baseline symptom profiles. While both active treatments were significantly better
      than placebo in relieving the pain and associated symptoms of migraine, AAC was
      superior to IB for TOTPAR2, as well as for PAR, time to onset of meaningful PAR,
      pain intensity reduction, headache response, and pain free. The mean TOTPAR2
      scores for AAC, IB, and placebo were 2.7, 2.4, and 2.0, respectively (AAC vs. IB,
      P < .03). The median time to meaningful PAR for AAC was 20 minutes earlier than
      that of IB (P < .036). CONCLUSION: AAC and IB are safe, cost-effective treatments
      for migraine; AAC provides significantly superior efficacy and speed of onset
      compared with IB.

PMID- 16618264
TI  - Characteristic and overlapping features of migraine and tension-type headache.
AB  - OBJECTIVE: This epidemiological survey was conducted to investigate comprehensive
      characteristic and overlapping features of migraine and tension-type headache
      (TTH) disorders classified based on International Classification of Headache
      Disorders-II. METHODS: The stratified cohort of this study was composed of 2504
      schoolchildren aged 10 to 17 years. A 38-item questionnaire inquiring all
      characteristic features of primary headache syndromes mandatory for
      classification was applied to selected 483 children with recurrent headache in
      the last 6 months. RESULTS: Migraine was diagnosed in 227 (47.0%) of 483 children
      and TTH in 154 (31.9%). Out of 125 children with definite migraine, 73 (58.4%)
      reported tension-type symptoms and 94 (68.1%) of 138 children with definite TTH
      reported migraine-type symptoms. Pressing pain (21%) and lack of aggravation of
      pain by physical activity (34%) were the major tension-type features in patients
      with migraine. Throbbing quality (43%) and aggravation by physical activity (30%)
      determined the main migraine-type features in patients with TTH. CONCLUSION: The
      frequent co-occurrence of migraine and TTH symptoms suggests the presence of a
      common pathogenesis.

PMID- 16618263
TI  - Trigger points in the suboccipital muscles and forward head posture in tension
      type headache.
AB  - OBJECTIVE: To assess the presence of trigger points (TrPs) in the suboccipital
      muscles and forward head posture (FHP) in subjects with chronic tension-type
      headache (CTTH) and in healthy subjects, and to evaluate the relationship of TrPs
      and FHP with headache intensity, duration, and frequency. BACKGROUND: Tension
      type headache (TTH) is a prototypical headache in which myofascial TrPs in the
      cervical and pericranial musculature can play an important role. DESIGN: A
      blinded, controlled pilot study. METHODS: Twenty CTTH subjects and 20 matched
      controls without headache participated. TrPs were identified by eliciting
      referred pain with palpation, and increased referred pain with muscle
      contraction. Side-view pictures of each subject were taken in sitting and
      standing positions, in order to assess FHP by measuring the craniovertebral
      angle. Both measures were taken by a blinded assessor. A headache diary was kept
      for 4 weeks in order to assess headache intensity, frequency, and duration.
      RESULTS: Sixty-five percent (13/20) CTTH subjects showed active TrPs and 35%
      (7/20) had latent TrPs in the suboccipital muscles. Six (30%) controls also had
      latent TrPs. Differences in the presence of suboccipital muscle TrPs between both
      the groups were significant for active TrPs (P < .001) but not for latent TrPs (P
      > .5). CTTH subjects with active TrPs reported a greater headache intensity and
      frequency than those with latent TrPs (P < .05). The degree of FHP was greater in
      CTTH subjects than in controls in both sitting and standing positions (P < .01).
      Within the CTTH group, there was a negative correlation between the
      craniovertebral angle and the frequency of headache (r(s) = -0.6, P < .01, in
      sitting position; r(s) = -0.5, P < .05, in standing position). CTTH subjects with
      active TrPs had a greater FHP than those with latent TrPs, though this difference
      was not significant. CONCLUSIONS: Suboccipital active TrPs and FHP were
      associated with CTTH. CCTH subjects with active TrPs reported a greater headache
      intensity and frequency than those with latent TrPs. The degree of FHP correlated
      positively with headache duration, headache frequency, and the presence of
      suboccipital active TrPs.

PMID- 16618266
TI  - Contribution of serotonin transporter gene polymorphisms to pediatric migraine.
AB  - BACKGROUND: The serotonin transporter gene is a promising candidate locus for the
      genetic susceptibility of migraine. OBJECTIVE: Two functional polymorphisms of
      the serotonin transporter gene (5-HTTLPR and STin2) were analyzed to assess
      whether these variants are associated with pediatric migraine. METHODS: Eighty
      seven Hungarian pediatric migraine patients and 464 controls were genotyped using
      polymerase chain reaction. Patients suffering from migraine with (n = 38) or
      without aura (n = 49) were interviewed regarding the clinical symptoms before or
      during the attacks. RESULTS: There was no difference between genotype or allele
      distribution of 5-HTTLPR and STin2 polymorphisms in the entire group of
      migraineurs and controls. Analysis of subgroups showed an association between
      STin2 and migraine with aura, as the 12,12 homozygote genotype was
      overrepresented in this group of patients. Furthermore, similar allele and
      genotype patterns were found in cases with severe vomiting and abdominal pain.
      CONCLUSIONS: These results confirm and extend the association between the STin2
      polymorphism of 5-HTT gene and migraine with aura using pediatric probands. Our
      data also suggest a novel endophenotype for pediatric migraine characterized by
      excessive vomiting and abdominal pain during the attack.

PMID- 16618267
TI  - Endothelin receptor A -231 G>A polymorphism: no linkage to primary pediatric
      headache.
AB  - OBJECTIVE: To assess whether the biallelic -231 G>A polymorphism of the
      endothelin type A receptor (EDNRA) gene, previously shown to be a marker of
      increased risk for developing migraine, has a role in the susceptibility to
      primary pediatric headache. BACKGROUND: Several studies suggest that endothelin
      has a role in migraine. A recent association study has shown that the biallelic 
      231 G>A polymorphism of the EDNRA gene is associated to migraine in an elderly
      population. METHODS: A total of 126 consecutive unrelated pediatric patients
      affected by primary headache, classified according to the International Headache
      Society criteria in migraine (migraine with aura, n = 3; migraine without aura, n
      = 80), and tension-type headache (episodic tension-type headache, n = 36; chronic
      tension-type headache, n = 7) patients, were recruited to the study. Sixty-seven
      healthy blood donors were used as a control group. Genomic DNA was extracted from
      buccal swabs or blood samples and analyzed by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) for the above-mentioned
      polymorphism. Allele and genotype frequencies for primary headache patients were
      analyzed in comparison with the control group. RESULTS: No significant
      differences were found in the distribution of the EDNRA -231 G>A polymorphic
      variant when considering both genotype (migraine chi2 = 2.78, P = .25; tension
      type headache chi2 = 3.58, P = .17) and allelic frequencies (migraine chi2 =
      1.48, P = .22; tension-type headache chi2 = 0.39, P = .56). Furthermore, no
      significant genotype-related difference was found in relation to clinical
      features, such as age at onset, frequency, and length of the attacks.
      CONCLUSIONS: Our study shows that the -231 G>A polymorphism in the EDNRA gene is
      neither associated with primary juvenile headache nor significantly correlated
      with main clinical features characteristic of the headache pathology in pediatric
      settings.

PMID- 16618269
TI  - Open-label trial of cinnarizine in migraine prophylaxis.
AB  - OBJECTIVE: To assess the effectiveness and safety of cinnarizine as a migraine
      preventive therapy. METHODS: Sixty patients with more than 2 migraine headache
      attacks during a 4-week baseline entered the study and received a 25-mg tablet
      cinnarizine twice daily for the first 3 days and then 3 times daily. They were
      assessed on weeks 2, 6, 10, and 14. Reduction from baseline in 4-week migraine
      headache rate was the primary efficacy variable. Reduction in migraine attacks
      duration and severity was also evaluated. RESULTS: The mean reduction in 4-week
      migraine headache rate was 4.6 +/- 2.2 from the baseline of 6.2 +/- 2.2 after 14
      weeks of treatment, which was statistically significant (P < 0.001). Percent
      reduction in 4-week migraine frequency was 35% after 2 weeks, 74% after 6 weeks,
      74% after 10 weeks, and 75% after 14 weeks of treatment. Significant reduction in
      attack duration (P < 0.001) and severity (P < 0.001) was also noted. No serious
      adverse events were observed in this series of patient. CONCLUSION: Cinnarizine
      is an efficacious and well-tolerated prophylactic antimigraine medication, which
      has early onset effectiveness.

PMID- 16618268
TI  - Thomas Jefferson's headaches: were they migraines?
AB  - Thomas Jefferson had severe headaches on a number of occasions during his adult
      life, as noted by most of his biographers. Some occurred during important
      historical events, including the period just before the writing of the
      Declaration of Independence. Historians generally have considered these headaches
      to be migraines, while some physician authors have considered the alternative
      diagnoses of tension-type headaches and cluster headaches. A review of the
      literature, including Jefferson's many letters, suggests that they probably were
      migraines, although not all of the current diagnostic criteria can be met.

PMID- 16618270
TI  - Prevention of migraine with olmesartan in patients with
      hypertension/prehypertension.
AB  - OBJECTIVE: To explore the effects of olmesartan on frequency and severity of
      migraine attacks in patients with comorbid hypertension and prehypertension.
      BACKGROUND: A randomized, double-blind, placebo-controlled, crossover study with
      a total of 60 patients has demonstrated the efficacy and safety of the
      angiotensin II receptor blocker candesartan in migraine prophylaxis. We study the
      potential efficacy and tolerability of olmesartan in preventing migraine in
      patients with hypertension and prehypertension. DESIGN/METHODS: Twenty-four
      adults, aged 27 through 76, with either hypertension or prehypertension, were
      included in this open-label study. Participants suffered from migraines
      (diagnosed according to International Headache Society classifications) for at
      least 3 months. Patients were treated with 10 to 40 mg of olmesartan per various
      observational periods of at least 3 months. Frequency and severity were recorded
      by office visits or by telephonic interview. RESULTS: Patients reported an 82.5%
      average reduction in the frequency of migraine attacks. Patients also experienced
      a 45% average reduction in the severity of migraine attacks measured on a numeric
      pain scale of 1 to 10. The only undesired effect was dizziness or presyncope. No
      serious adverse events occurred and no adverse event caused a premature
      termination. Two patients had no reduction in headache frequency, intensity, and
      blood pressure. CONCLUSIONS: The favorable results and low rate of adverse
      effects, in this open migraine prevention study in patients with hypertension or
      prehypertension, are similar to results of the randomized, double-blind, placebo
      controlled, crossover study in patients taking candesartan. Olmesartan shows a
      potential as an effective and well-tolerated migraine prophylactic agent for
      patients with comorbid hypertension and prehypertension.

PMID- 16618271
TI  - Treatment of idiopathic intracranial hypotension: cervicothoracic and lumbar
      blood patch and peroral steroid treatment.
AB  - METHODS: Twelve consecutive patients with clinical symptoms and testing results
      compatible with a diagnosis of idiopathic intracranial hypotension (IIH), but no
      identifiable site of cerebrospinal fluid (CSF) leakage, were treated with a
      cervicothoracic or lumbar epidural "blood patch" (EBP) or orally administered
      steroids. RESULTS: Prompt and complete relief from headache persisting for at
      least 4 months was attained in 3 of 4 treatments with cervicothoracic EBP, 2 of
      15 with lumbar EBP, and 4 of 8 with steroids. CONCLUSION: These results suggest
      that in patients who presumably suffer from IIH and yet have no identifiable site
      of CSF leakage, the presumed leakage more often occurs at the cervicothoracic
      level than the lumbar. In addition, our experience suggests that some IIH
      patients may be treated effectively with oral steroids and a trial of such
      therapy may be considered as an alternative to EBP.

PMID- 16618272
TI  - Thunderclap headache, cardiopulmonary arrest, and myocardial infarction.

PMID- 16618273
TI  - Migraine versus probable migraine.

PMID- 16618274
TI  - Migraine triggered by sucralose--a case report.
AB  - Sucralose is the active compound of the most commonly sold sweetener in the
      United States. Different than aspartame, sucralose is not considered to be a
      migraine trigger. Herein we report a patient with attacks of migraine
      consistently triggered by sucralose. She also suffers from menstrually related
      migraine that had been well-controlled for several months since she switched her
      contraceptive from fixed estrogen to triphasic contraceptive pills. Some attacks
      triggered by sucralose were preceded by aura, and she had never experienced
      migraine with aura before. Withdrawal of the compound was associated with
      complete resolution of the attacks. Single-blind exposure (vs. sugar) triggered
      the attacks, after an attack-free period.

PMID- 16618277
TI  - Chronic long-standing headache due to neurocysticercosis.
AB  - A 35-year-old Chinese woman presented with a 26-year history of persistent
      headache, relieved only by diuretics. Characteristic CT findings, peripheral
      eosinophilia, lymphocytic CSF pleocytosis, elevated CSF IgG, positive oligoclonal
      bands, antibody-positive ELISA, and Western blot results with Taenia solium
      antigen, and a favorable response to albendazole led to the diagnosis of
      neurocysticercosis.

PMID- 16618276
TI  - Thunderclap stroke: embolic cerebellar infarcts presenting as thunderclap
      headache.
AB  - Thunderclap headache is known to be a presenting feature of subarachnoid
      hemorrhage, unruptured intracranial aneurysm, cerebral venous thrombosis,
      cervical artery dissection, spontaneous intracranial hypotension, pituitary
      apoplexy, retroclival hematoma, and hypertensive reversible posterior
      leukoencephalopathy. We describe a case of thunderclap headache in the absence of
      focal, long-tract, or lateralizing neurological findings, as the primary clinical
      feature of embolic cerebellar infarcts. This case expands the differential
      diagnosis of thunderclap headache and reinforces the need for magnetic resonance
      imaging in the evaluation of such patients, even when neurologic examination,
      brain computed tomography, and cerebrospinal fluid analysis are normal.

PMID- 16618275
TI  - Thunderclap headache from complicated sinusitis.
AB  - We report a case of complicated pansinusitis presenting with thunderclap
      headache. The patient quickly developed left ophthalmoplegia and imaging
      demonstrated extension of inflammation from the sphenoid sinus into the sellar
      region. Thunderclap headache is well known to occur from a variety of
      intracranial events, but complicated sinusitis presenting this way is seldom
      described. The patient recovered completely with appropriate treatment.

PMID- 16618278
TI  - Hemicrania continua: a case in which a patient experienced complete relief on
      melatonin.
AB  - This paper reports a case of hemicrania continua in which attacks were
      successfully eliminated while taking melatonin 7 mg at bedtime after the patient
      was no longer able to tolerate indomethacin due to gastrointestinal side effects.

PMID- 16618281
TI  - As fast gets faster, have we lost touch with our purpose?

PMID- 16618279
TI  - Regarding botulinum toxin for the prophylaxis of chronic daily headache.

PMID- 16618282
TI  - Feverfew for migraine prophylaxis.

PMID- 16618284
TI  - Periodicity of migraine.

PMID- 16618285
TI  - Acupuncture in trigeminal neuralgia management.

PMID- 16618290
TI  - Measuring anesthesia in children using the EEG.
AB  - Advances in electroencephalogram (EEG) processing have produced new interest in
      measuring anesthesia using the EEG. There are a number of EEG-based anesthesia
      'depth' monitors now available and their use in pediatric anesthesia is
      increasing. Although these monitors have been extensively studied in adults,
      there are relatively few studies examining their validity or use in children. To
      some extent we must rely on adult data. However, extrapolation of data from
      adults to children requires an in depth understanding of the physiology behind
      the data. The first question is what is being measured. What is anesthesia? A
      model of anesthesia has several components with arousal as a core component.
      Arousal can be linked to clinical observations, and correlates with anatomical
      and physiological studies. The EEG has characteristics that fairly consistently
      change with arousal during anesthesia, but the relationship between arousal and
      the EEG is imprecise and drug dependent. This relationship is the basis for using
      the EEG to measure anesthesia and provides only an indirect measure of
      consciousness and memory formation. A good understanding of how the EEG is
      related to anesthesia is essential when interpreting the EEG during anesthesia,
      and especially when extending the use of the EEG to measure anesthesia in
      children. Physiological studies in adults and children indicate that EEG-derived
      anesthesia depth monitors can provide an imprecise and drug-dependent measure of
      arousal. Although the outputs from these monitors do not closely represent any
      true physiological entity, they can be used as guides for anesthesia and in so
      doing have improved outcomes in adults. In older children the physiology, anatomy
      and clinical observations indicate the performance of the monitors may be similar
      to that in adults, although the clinical relevance of outcomes may be different.
      In infants their use cannot yet be supported in theory or in practice.

PMID- 16618289
TI  - Attention-deficit hyperactivity disorder and anesthesia.

PMID- 16618293
TI  - Comparative evaluation of different doses of propofol preceded by fentanyl on
      intubating conditions and pressor response during tracheal intubation without
      muscle relaxants.
AB  - BACKGROUND: The aim of our study was to determine the optimal dose of propofol
      preceded by fentanyl for successful tracheal intubation and to see its
      effectiveness in blunting pressor response in children aged 3-10 years. METHODS:
      This prospective, double blind, randomized study was conducted on 60 ASA grade I
      and II children, between 3 and 10 years undergoing elective surgery who were
      divided into three groups of 20 each. The children received different doses of
      propofol (group I, 2.5 mg x kg(-1); group II, 3.0 mg x kg(-1); group III, 3.5 mg
      x kg(-1)) preceded by a fixed dose of fentanyl (3.0 microg x kg(-1)) 3 min
      earlier. The tracheal intubating conditions were graded based on scoring system
      devised by Helbo-Hensen et al. with Steyn modification which includes five
      criteria; ease of laryngoscopy, degree of coughing, position of vocal cords, jaw
      relaxation, and limb movement and graded on a 4-point scale. Heart rate (HR),
      mean arterial pressure (MAP), and oxygen saturation changes were also noted.
      RESULTS: Tracheal intubating conditions were acceptable in 25% of the patients in
      group I, while significantly higher (P < 0.001) in group II (80%) and in group
      III (90%). The pressor response was not effectively blunted in group I (17%
      increase in HR), while effectively blunted in groups II and III. A fall in
      cardiac output was seen in group III indicated by a decrease in MAP (16%) and HR
      (11%). No airway complications were noted. CONCLUSIONS: Propofol 3 mg x kg(-1)
      (group II) preceded by fentanyl 3 microg x kg(-1) is the optimal dose combination
      in our study. It provides acceptable intubating conditions in 80% patients,
      blunts pressor response to intubation without significant cardiovascular
      depression.

PMID- 16618292
TI  - Comparison of three sites to check the pulse and count heart rate in hypotensive
      infants.
AB  - BACKGROUND: Current international guidelines state that heart rate counted at the
      brachial pulse must be absent or <60 b x min(-1) to diagnose cardiac arrest. Some
      data suggest that this site may not be the best to check cardiac activity.
      Hypotension is a likely real scenario of the need for chest compressions in
      infants. We compared the performance of three sites of pulse palpation (brachial,
      carotid, and femoral) for detecting and counting heartbeat in hypotensive
      infants. METHODS: In an operating theater of a pediatric teaching hospital in
      Italy, we studied 40 anesthetized hypotensive infants just prior to surgery,
      checked by two doctors and two nurses by a cross-sectional, repeated-measures
      study design. Each examiner, blind to the monitoring data of the patient, was
      asked to find the infant's arterial pulse within 10 s and count heart rate for 15
      s. During each examination, the order of the three sites was randomized. RESULTS:
      Among successful detections, femoral pulse palpation resulted as the most
      successful, rapid, and accurate site to detect and count heart rate in
      hypotensive infants. CONCLUSIONS: Femoral palpation proved to be the best site
      for detecting heartbeat and counting heart rate in hypotensive infants. These
      findings challenge the current guidelines. More data are needed, but the current
      standard of brachial pulse assessment is debatable.

PMID- 16618291
TI  - Performance of a pediatric ambulatory anesthesia program--a developing country
      experience.
AB  - BACKGROUND: The aim of this study was to evaluate the performance of a pediatric
      ambulatory anesthesia program in a tertiary care teaching hospital in a
      developing country. METHODS: Data on all pediatric patients (<16 years of age)
      scheduled to have elective day-care surgery during a 1 year period from January
      1999 to December 1999 were collected retrospectively. An audit form was used to
      determine the specialty of the procedures, anesthesia techniques, postoperative
      analgesia, perioperative complications, unplanned admissions and outcomes with
      respect to morbidity and mortality. RESULTS: A total of 763 pediatric ambulatory
      surgical procedures were performed during the year of 1999. The procedures
      included general surgery, ENT, orthopedic and plastic surgery. The most common
      procedure was inguinal hernia repair followed by umbilical hernia repair,
      adenotonsillectomy and circumcision and 96% of the patients had general
      anesthesia. There were only three unplanned admissions (0.4%); one for a surgical
      reason and two for anesthetic reasons. There was no serious morbidity or
      mortality in any patient. CONCLUSIONS: Performance of pediatric day-care
      anesthesia has been good in our day-care unit and we have a successful ambulatory
      surgery program, despite the limitations of a developing country.

PMID- 16618294
TI  - A pilot study of the rectus sheath block for pain control after umbilical hernia
      repair.
AB  - BACKGROUND: Umbilical hernia repair, a common day surgery procedure in children,
      is associated with significant postoperative discomfort. The rectus sheath block
      may offer improved pain management following umbilical hernia repair. In this
      pilot study, we compared the efficacy of the rectus sheath block with that of our
      current standard practice--local anesthetic infiltration into the surgical wound-
      for pain control after umbilical hernia repair in children. METHODS: Fourteen
      children, aged 1-8 years, undergoing umbilical hernia repair were randomly
      assigned to receive either a rectus sheath block or local anesthetic infiltration
      into the surgical wound at completion of surgery. Anesthetic management was
      standardized. Each analgesic technique was performed using 0.8 ml x kg(-1) of
      0.25% bupivacaine with epinephrine 1:200,000. Postoperatively, an investigator
      who was blinded to the analgesic technique recorded the Children's Hospital of
      Eastern Ontario Pain Scale (CHEOPS) scores and sedation scores every 10 min, and
      administered intravenous morphine 50 microg x kg(-1) for cases with CHEOPS scores
      > or = 8. Total morphine dose was recorded. Parents were telephoned the day after
      surgery to determine the overall satisfaction with pain control. RESULTS: Total
      postoperative morphine consumption did not differ significantly between groups,
      averaging 0.10 +/- 0.09 and 0.10 +/- 0.07 mg x kg(-1) for the local infiltration
      and rectus sheath groups, respectively. There were no significant differences in
      pain or sedation scores, and no complications related to either analgesic
      technique. DISCUSSION: Our results suggest that the rectus sheath block has no
      advantage over infiltration of local anesthetic into the surgical wound for
      postoperative pain management in children undergoing umbilical hernia repair.

PMID- 16618295
TI  - Heating capabilities of the Hotline and Autoline at low flow rates.
AB  - BACKGROUND: At low flow rates, fluid warmers using coaxial warming tubes are
      superior in preventing heat loss. This laboratory investigation was performed in
      order to compare the heating capabilities of two coaxial fluid warmers. METHODS:
      The Hotline and the Autoline were investigated by using normal saline at various
      flow rates (10-99 ml x h(-1)). Final infusion temperatures were measured six
      times in a row at the end of the tubing by using a rapid-response thermometer.
      Final temperatures were compared with those of infusions, which passed through
      disposable i.v. tubing covered and warmed using an 'off label' convective air
      warming system (WarmTouch). Measurements were performed at two different room
      temperatures (20 and 24 degrees C). Each group was analyzed with respect to
      differences between various flow rates as well as differences between the groups
      at comparable flow rates by using a three-way anova with multiple comparisons
      according to Tukey's procedure. Significance was defined at P < 0.05. RESULTS:
      Both devices heat infusions at low flow rates efficiently above 34 degrees C,
      with the Hotline being more effective than the Autoline (P < 0.0001). Except for
      the lowest flow rate (10 ml x h(-1)), the Hotline delivered infusion temperatures
      between 38 and 39 degrees C, while the Autoline warmed the infusions upto 36
      degrees C. While heating capability of the Hotline was improved with elevated
      room temperatures at low flow rates (10-60 and 80 ml x h(-1)), the Autoline
      demonstrated lower infusion temperatures throughout elevated room temperature at
      flow rates between 20 and 90 ml x h(-1). Both devices heated infusions more
      efficiently compared with 'off label used' convective air warmer (each with P <
      0.0001). CONCLUSIONS: Both the Hotline and the Autoline heated infusions
      sufficiently at low flow rates. However, the heating capability of the Hotline
      was superior and can further be increased at low flow rates by increasing the
      room temperature.

PMID- 16618296
TI  - The pharmacokinetics of a single rectal dose of paracetamol (40 mg x kg(-1)) in
      children with liver disease.
AB  - BACKGROUND: The aim of our study was to measure the serum paracetamol
      concentrations achieved following a single rectal loading dose of 40 mg x kg(-1)
      in children with chronic liver disease. METHODS: We recruited 17 children (3-15
      years, 10.6-75 kg) undergoing minor surgical procedures under general anesthesia.
      Paracetamol was administered at the end of surgery and blood samples were taken
      for analysis at 2, 3, 4, 6 and 8 h postdose. RESULTS: The mean Cmax of 11.4 mg x
      l(-1) [coefficient of variation (CV) 66%] was achieved at a Tmax of 2.7 h (CV
      42%). The relative bioavailability (F) of the suppository formulation was not
      estimated, but clearance (Cl/F) estimates 0.73 l x kg(-1) x h(-1) (CV 87%) and
      time-concentration profiles for these children were similar to the normal
      pediatric population. CONCLUSIONS: There are currently no biologic markers
      available for monitoring possible hepatotoxicity in this cohort of patients with
      liver disease, but our data suggest that a single-dose suppository is a
      satisfactory analgesic alternative.

PMID- 16618297
TI  - Safety of ketorolac in neonates and infants after cardiac surgery.
AB  - BACKGROUND: Ketorolac is an injectable nonsteroidal anti-inflammatory drug that
      is often used as a transitional short-term analgesic to treat moderate pain and
      to decrease opioid use. There is a paucity of literature documenting the safety
      of using ketorolac in neonates and infants after cardiac surgery. METHODS: A
      retrospective chart review was performed which identified all patients <6 months
      of age who received ketorolac after cardiac surgery. Patients' demographic,
      surgical, and dosing data were collected. A Student's t-test was used to identify
      significant differences in renal and hematologic laboratory values at baseline
      and at 48 h of treatment. RESULTS: A total of 53 children <6 months of age
      received at least one dose of ketorolac after cardiac surgery. Eleven of 53
      children (21%) were <1 month of age. The blood urea nitrogen/serum creatinine
      (SCr) levels increased from baseline at 48 h of therapy in all infants, but
      stayed within normal limits. The largest increase in SCr level from baseline on
      any day of ketorolac therapy was 26 micromol x l(-1) (0.3 mg x dl(-1)) which
      occurred in two neonates. Four patients (three infants and one neonate) had minor
      episodes of bleeding while being treated with ketorolac. There were no clinically
      significant changes in hemoglobin, hematocrit or platelet count. None of these
      episodes caused hemodynamic instability nor required transfusion of blood
      products. CONCLUSIONS: Ketorolac was used safely in neonates and infants who have
      had cardiac surgery at our institution. Ketorolac was not associated with any
      adverse hematologic or renal effects. Prospective investigation is warranted to
      further assess the safety and effectiveness of ketorolac in this patient
      population.

PMID- 16618298
TI  - A trial of fresh autologous whole blood to treat dilutional coagulopathy
      following cardiopulmonary bypass in infants.
AB  - BACKGROUND: Transfusion of fresh whole blood is superior to blood component
      therapy in correcting coagulopathies in children following cardiopulmonary bypass
      (CPB); however, a supply of fresh homologous whole blood is difficult to
      maintain. We hypothesized that transfusion of fresh autologous whole blood
      obtained prior to heparinization for CPB and infused following CPB would be
      associated with improved coagulation function when compared with standard
      therapy. METHODS: A total of 32 infants 5-12 kg undergoing noncomplex open
      cardiac surgery were randomly assigned to either the treatment or control group.
      In the treatment group, 15 ml x kg(-1) of autologous whole blood was collected
      into a CPDA bag prior to heparinization while 15 ml x kg(-1) of 5% albumin was
      infused intravenously. After reversal of heparin, coagulation tests were drawn in
      both groups, and the autologous whole blood was infused over 20 min in the
      treatment group. RESULTS: The treatment group had greater (P < 0.05) improvement
      in platelet count, prothrombin time, and fibrinogen than the control group.
      CONCLUSIONS: We conclude that collection of fresh autologous whole blood prior to
      heparinization and reinfusion following CPB is associated with greater
      improvement of coagulation status after CPB in infants.

PMID- 16618302
TI  - Anesthetic management of a child with chromosome 22q11 deletion syndrome.
AB  - Chromosome 22q11 deletion syndrome (22q11DS) is a congenital anomaly
      characterized by cardiovascular, oropharyngeal, immunologic, endocrine, and
      neurodevelopmental abnormalities. We successfully managed a 6-year-old girl with
      22q11DS with general anesthesia. Potential problems in anesthetic management of
      patients with 22q11DS are reviewed.

PMID- 16618304
TI  - Suspected malignant hyperthermia in a child with laminin alpha2 (merosin)
      deficiency in the absence of a triggering agent.
AB  - Malignant hyperthermia (MH) is an inherited disorder of the skeletal muscles that
      can be triggered by many anesthetic agents. MH has different presentations and
      manifestations that makes it difficult to diagnose. Patients with laminin alpha2
      deficiency have never been reported to be susceptible to MH. We present a
      suspected MH episode in the absence of classic triggering agents in a 7-year-old
      boy with laminin alpha2 (merosin) deficiency and congenital muscular dystrophy.
      The episode was diagnosed using the MH clinical grading scale and responded well
      to prompt management with dantrolene. We conclude that patients with laminin
      alpha2 deficiency may be susceptible to MH, and early suspicion and rapid
      treatment is vital in the management of MH. Anesthesiologists should be prepared
      to treat MH in susceptible patients even in the absence of a classical triggering
      agent.

PMID- 16618303
TI  - Video assisted fiberoptic intubation for temporomandibular ankylosis.
AB  - In the era of fiberoptics, securing of the airway under general anesthesia in
      small children with temporomandibular joint ankylosis without a flexible
      pediatric fiberoptic endoscope requires considerable skill. We describe the use
      of an adult flexible fiberoptic laryngoscope with a video camera system to
      visualize the glottis from one nostril while the tracheal tube was passed from
      the other nostril.

PMID- 16618300
TI  - Early vs late intraoperative administration of tropisetron for the prevention of
      nausea and vomiting in children undergoing tonsillectomy and/or adenoidectomy.
AB  - BACKGROUND: Tropisetron is a long-acting 5HT3 receptor antagonist and was shown
      to be effective in the prevention of postoperative nausea and vomiting (PONV)
      after tonsillectomy. The aim of the study was to compare the effects of early vs
      late intraoperative administration of tropisetron with regard to prevention of
      PONV during the first 48 h after extubation. METHODS: In a randomized double
      blind study, we investigated 120 children aged 1-12 years undergoing general
      anesthesia for tonsillectomy or adenotonsillectomy. Patients received 0.1 mg x
      kg(-1) tropisetron (maximum 2 mg) immediately after inhalational induction
      (early) and establishment of intravenous access or after the end of surgery
      before extubation (late). PONV and the need for antiemetic rescue medications
      were recorded within the following 48 h. Patient data were analyzed using t-test,
      chi-squared test (significance level of alpha = 0.05) and Spearman rank
      correlation test. RESULTS: The overall incidence of vomiting was 55.3%, with 60%
      (36/60) in the early treatment and 51.6% (31/60) in the late treatment group (P =
      0.46). The observed time course 48 h postoperatively showed no difference
      regarding the number of vomiting episodes between the two groups and the need for
      antiemetic rescue medication. The incidence of nausea was higher in the late
      application group in the first 6 h after extubation (P = 0.001) and higher in the
      early application group between 24 and 48 h after extubation (P = 0.02). Morphine
      and the age over 3 years had a strong influence on the incidence of vomiting.
      CONCLUSION: The intraoperative time point (early vs late) of intravenous
      administration of a single prophylactic dose of tropisetron has no impact on the
      incidence of PONV during the first 48 h after tonsillectomy and/or adenoidectomy
      in children.

PMID- 16618299
TI  - Postoperative continuous intrathecal pain treatment in children after selective
      dorsal rhizotomy with bupivacaine and two different morphine doses.
AB  - BACKGROUND: Children undergoing selective dorsal rhizotomy (SDR) experience
      severe pain postoperatively; a pain related to both the extensive surgical
      exposure with multilevel laminectomy and nerve root manipulation. We sought to
      define an optimal dose of continuous intrathecal (IT) morphine and bupivacaine to
      treat this severe pain. The aim of this study was to compare two different
      concentrations of morphine in a fixed dose of bupivacaine with regard to the
      analgesic effect and survey if they differed in side effects. METHODS: Twenty-six
      children, aged 2.7-7.4 years undergoing SDR were included in this study.
      Postoperatively 11 children received a continuous infusion of morphine 0.4 microg
      x kg(-1) x h(-1) and bupivacaine 40 microg x kg(-1) x h(-1) (low-dose group) and
      15, a continuous infusion of morphine 0.6 microg x kg(-1) x h(-1) and bupivacaine
      40 microg x kg(-1) x h(-1) (high-dose group). The Behavioral Observational Pain
      Scale (BOPS) was used to evaluate pain. RESULTS: Better pain relief was obtained
      in the high-dose group seen in lower BOPS score compared with the low-dose group
      [P = 0.03, Fisher's permutation test and P = 0.06 Wilcoxon-Mann-Whitney (WMW)
      test]. The low-dose group received seven times as much ketobemidone 0.43 +/- 0.54
      mg x kg(-1) 48 h(-1) compared with 0.06 +/- 0.09 mg x kg(-1) 48 h(-1) in the high
      dose group (P = 0.0005 Fisher's permutation test, P = 0.0017 WMW test). There was
      no statistical difference in pruritus and postoperative nausea and vomiting
      between the groups. Respiratory and hemodynamic depression was not found.
      CONCLUSION: This study shows that, compared with low-dose, the higher dose of
      continuous IT morphine combined with bupivacaine, significantly reduce pain score
      and postoperative intravenous analgesic requirements without increasing adverse
      effects.

PMID- 16618301
TI  - Intraoperative wake-up test in neonatal neurosurgery.
AB  - Intraoperative wake-up test (WPT) still remains the gold standard to monitor
      anterior spinal cord function during spinal surgery. However, the test requires
      patient cooperation and hence difficult to perform in very young children or
      mentally challenged. In this report, we describe a WPT in a newborn during
      surgical repair of a large myelomeningocele. We relied on mivacurium for
      intubation and the relaxant effect was allowed to wear-off to permit the use of
      intraoperative nerve stimulator. We used desflurane and propofol infusion for
      rapid titration of the anesthetic depth and BIS monitor to 'gauge' the
      'wakefulness' of the child during the WPT. We employed lidocaine infusion to
      improve tolerance to the tracheal tube and to bestow beneficial effect on
      intracranial pressure during surgery and the WPT. The results of the WPT were
      judged to be satisfactory after confirming flexion and extension of the lower
      extremities at the hip and knee level, correlating it with the BIS values, and
      comparing it with the preoperative status. Frequently associated prematurity,
      higher possibility of remaining intubated in the immediate postoperative period
      and any new onset neurologic deficit not becoming apparent until after extubation
      makes intraoperative neuromonitoring relevant in this age group. Our methodology
      of management has permitted us to perform a delicate test safely and will allow
      us to repeat the WPT if needed during neonatal neurosurgery.

PMID- 16618308
TI  - Delayed ventricular fibrillation following blunt chest trauma in a 4-year-old
      child.
AB  - A 4-year-old boy who was involved in a motor vehicle accident as a pedestrian and
      suffered blunt chest trauma was admitted to the emergency room. Unpredictable
      delayed ventricular fibrillation was diagnosed and treated successfully 2 h
      later. This case cannot be classified as commotio cordis as the ventricular
      fibrillation (VF) developed so long after the sustained chest injury. At the same
      time, other possible etiologies of VF such as cardiac pathology or electrolyte
      and metabolic disorders had been ruled out. Thus, an etiological link between the
      chest trauma and the subsequent VF could not be ruled out and is in fact
      plausible despite the late onset.

PMID- 16618305
TI  - Use of BIS monitor in a child with congenital insensitivity to pain with
      anhidrosis.
AB  - We describe a case of a 14-year-old boy with congenital insensitivity to pain and
      anhidrosis (CIPA) who underwent tarsal tunnel release for tarsal tunnel syndrome.
      Because of abnormal pain perception, the patient's response to normally painful
      surgical stimuli is severely impaired and not adequately reflected in a
      corresponding rise in blood pressure or heart rate. This lack of autonomic
      feedback to pain stimuli may make it more difficult to assess whether anesthetic
      depth is adequate to prevent intraoperative awareness and thus to safely conduct
      anesthesia, especially if muscle paralysis is required for surgical indications.
      We describe for the first time the use of processed EEG monitoring with a BIS A
      2000 monitor to gauge anesthetic depth in a patient with CIPA. Initial forehead
      bispectral index (BIS) values prior to induction were normal (98) and then ranged
      between 23 and 79 during the whole surgical procedure. Propofol and lidocaine
      were used for induction and deep extubation; isoflurane was used as the sole
      anesthetic for maintenance with concentrations ranging from 0.21% to 0.92% to
      maintain a target BIS of 40-60. Volatile anesthetic requirements remained low
      throughout the procedure and no narcotics were necessary during surgery. The BIS
      monitor served as an adequate tool to help avoid excessive use of volatile
      anesthetic while assuring a processed EEG consistent with unconsciousness and
      amnesia. After the patient had recovered and was oriented to place and time in
      the recovery room, he was asked whether he remembered anything about the surgery
      and the presence of a breathing tube in his mouth. He denied any recall of such
      events.

PMID- 16618307
TI  - An unknown second tracheoesophageal fistula: a rare cause of postoperative
      respiratory failure.
AB  - The case of a 6-year-old boy who developed complications following gastric
      interposition surgery for severe, recurrent esophageal stricture is reported.
      Investigation of his pleural effusion revealed a rare and unexpected
      complication.

PMID- 16618309
TI  - A pediatric patient with a mediastinal mass and pulmonary embolus.
AB  - When anesthetizing a patient with an anterior mediastinal mass, sudden hypoxaemia
      and cardiovascular collapse may result from compression of a large airway or
      vascular structure in the mediastinum. We report the case of a pediatric cancer
      patient with an anterior mediastinal mass, who developed sudden and fatal
      hypoxaemia and cardiovascular collapse in the hours following sedation. A massive
      pulmonary thromboembolism was diagnosed at autopsy. We suggest that pulmonary
      embolism should be considered in the differential diagnosis when a patient with a
      mediastinal mass develops perioperative hypoxaemia, cardiovascular collapse, or
      both.

PMID- 16618306
TI  - Acquired long QT syndrome and elective anesthesia in children.
AB  - We present the case of a child who had had a previous episode of torsades de
      pointes (TdP) and who was scheduled for elective surgery under general
      anesthesia. The pathophysiology of this condition and the anesthesia concerns are
      discussed. An 8-year-old male with a history of osteogenic sarcoma had undergone
      an uneventful limb salvage procedure 2 years earlier. During a subsequent
      admission to the hospital, he had had a cardiopulmonary arrest with complete
      recovery. Telemetry electrocardiogram (ECG) rhythm recordings obtained during the
      event showed TdP that degenerated into ventricular fibrillation, which then
      terminated spontaneously. On a subsequent ECG, the QTc interval was 694 ms. The
      prolonged QT interval was attributed to homeopathic use of cesium chloride
      supplements and the QT interval normalized after cesium was stopped. He presented
      for an elective procedure and, with an anesthetic plan that emphasized
      medications without known effect on the QT interval, had an uneventful
      perioperative course. The optimal anesthesia plan for patients with prolonged QT
      or those suspected to be at risk for prolongation of the QT interval has not been
      well described. Available evidence suggests that using total intravenous
      anesthesia with propofol may be the safest and was used uneventfully in this
      case. Additionally, this case emphasizes the need to inquire about the use of
      supplements and naturopathic medications, even in children, that may have life
      threatening side effects or interactions with anesthetic agents.

PMID- 16618310
TI  - Management of congenital tracheal stenosis--using spontaneous ventilation to
      facilitate cardiopulmonary bypass.
AB  - We present an unusual case of an infant with life-threatening tracheal stenosis
      scheduled for repair utilizing cardiopulmonary bypass. After repeated attempts at
      intubation endtidal CO2 was absent. The child was eventually managed with
      spontaneous breathing sevoflurane via a facemask. The possible causes of absent
      endtidal CO2 after intubation are discussed.

PMID- 16618311
TI  - Bilateral hydronephrosis--a cause of increased airway pressure.

PMID- 16618313
TI  - Neuropathic pain.

PMID- 16618317
TI  - The debridement of hard to heal leg ulcers by means of a new device based on
      Fluidjet technology.
AB  - Debridement plays an essential role in the wound-bed preparation of necrotic and
      sloughy ulcers, being a mandatory step to achieve a well-debrided bed, proceeding
      towards healing. This study reports our experience with Versajet [Versajet
      Hydrosurgery System (Smith & Nephew, Hull, UK)], a new device for the debridement
      of exudating ulcers, based on Fluidjet technology, which excises and aspirates
      the unwanted tissue by using the Venturi effect. In a 10-month time period, a
      total of 68 patients, out of a setting of 167 patients, hospitalised as affected
      by chronic, hard-to-heal leg ulcers, stuck in the inflammatory phase, were
      treated with Versajet. Based on ulcer characteristics and clinical conditions,
      the remaining 99 patients underwent traditional debridement with moist dressings
      (controls). In the majority of Versajet-treated cases (46), an adequately
      debrided wound bed was achieved with one operative procedure; two and three
      procedures were required in 17 and 5 patients, respectively. Almost all the
      procedures were performed in the ward at the patient's bedside. This procedure is
      quick (mean time per treatment is about 5 minutes); when compared with a
      traditional treatment with moist dressings, Versajet considerably shortens the in
      hospital stay and promotes a quicker healing process. When used by an experienced
      surgeon, Versajet allows a selective debridement, as it makes it possible to
      remove only the tissue centred in the working end and spare the healthy tissue.
      Debriding with Versajet is highly effective in reducing the bacterial load of the
      ulcer bed. The pain caused by Versajet is well tolerated, especially when set for
      gentle debridement. If multiple treatments are required, the combined use with
      moist dressings is synergistic, as the dressings soften the necrotic tissue, thus
      facilitating the following Versajet debridement. The results indicate that
      Versajet offers more precision than standard mechanical debridement and, at high
      settings, offers an alternative to surgical debridement.

PMID- 16618316
TI  - High glucose inhibits human epidermal keratinocyte proliferation for cellular
      studies on diabetes mellitus.
AB  - In order to more clarify the delayed wound healing in diabetes mellitus, we
      cultured the human epidermal keratinocytes in both 6 mM (control group) and 12 mM
      glucose (high-glucose group) of "complete" MCDB 153 medium. Hyperglycaemia slowed
      the rate of their proliferation and inhibited their DNA synthesis and the
      production of total proteins. By 1 month after primary seeding in high-glucose
      group, the cells ceased their proliferation, whereas the cells in control group
      grew for more than 40 days. Mean population doublings in high-glucose group was
      5.27 (vs. 7.25 in control, P = 0.001), and mean population doubling time during 1
      month in high glucose group was 5.43 days (vs. 3.65 days in control, P = 0.02).
      They indicate that prolonged exposure to high glucose decreases the replicative
      life span of human epidermal keratinocytes in vitro. Furthermore, analysis of
      fatty acid contents in membrane phospholipids with thin-layer and gas
      chromatography showed no difference between the cultured keratinocytes in both
      conditions. Immunocytochemical staining of glucose transporter 1 shows that 28.1%
      of cells in high-glucose group were almost twice positive of those in control
      group (13.2%, P = 0.008). The mechanism of the ill effects of high glucose on
      epidermal keratinocytes is not so far clear, but it indicates the possibility of
      any direct effect of hyperglycaemia on glucose metabolism without changing lipid
      metabolism on cell membrane. The high-glucose group presented in this report can
      be available as an in vitro valuable study model of skin epidermal condition on
      diabetes mellitus.

PMID- 16618314
TI  - Psychiatric symptoms after anesthesia: antibiomania or Hoigne's syndrome?

PMID- 16618319
TI  - Eikinella corrodens wound infection in a diabetic foot: a brief report.
AB  - Eikinella corrodens normally forms part of the flora of the oral cavity and
      mucous membranes of the respiratory tract. It is usually associated with dental,
      head and neck infections (Cohen, Powderly, 2004, Infectious Diseases) and is
      considered to be an unusual cause of orthopaedic infections. We recently treated
      a diabetic patient with E. corrodens osteomyelitis of the fifth
      metatarsophalangeal joint, a phenomenon which has been reported in only three
      cases previously (Konugres et al., 1987, E. corrodens as a cause of osteomyelitis
      in the feet of the diabetic patients. Report of three cases). We recommend
      including E. corrodens in the spectrum of causative pathogens in diabetic foot
      infections.

PMID- 16618320
TI  - Segmental ulcerative vasculitis: a cutaneous manifestation of Takayasu's
      arteritis.
AB  - A 16-year-old girl with pyoderma gangrenosum (PG)-like skin lesions on the
      extremities, trunk and face developed Takayasu's arteritis (TA; pulseless
      disease). After 3 years under maintenance cyclosporin A therapy, the patient
      developed an ischaemic cerebral accident. Severe obstruction of both subclavian
      and left carotid arteries was found by Doppler sonography, angiography and
      computerised axial tomography. Evolution of this disease showed some
      characteristic findings: (a) PG-like lesions as the first cutaneous manifestation
      of pulseless disease; (b) methotrexate and cyclosporin A giving good results for
      the cutaneous lesions, but apparently not exerting an influence on the evolution
      of TA and the fatal outcome. This morphologic pattern may reflect underlying TA
      or Wegener's arteritis, and should be termed segmental ulcerative vasculitis.

PMID- 16618322
TI  - Scalp necrosis and giant cell arteritis: case report and issues in wound
      management.
AB  - Scalp necrosis is rare in patients with giant cell arteritis. Here, we report the
      case of an 81-year-old woman who presented with a management problem that
      required a truly multidisciplinary approach to treatment. A combined approach of
      effective wound bed preparation with selective debridement, prolonged
      antimicrobial therapy, corticosteroid use and careful dressing choices resulted
      in a successful outcome in a potentially disastrous situation.

PMID- 16618321
TI  - The effect of a silver-containing Hydrofiber dressing on superficial wound bed
      and bacterial balance of chronic wounds.
AB  - The treatment of chronic wounds represents a major cost to society and has a
      profound effect on the participant's quality of life. Chronic wounds may have an
      increased bacterial burden that can impair healing without all the clinical signs
      of infection. Silver dressings may provide an alternative topical method to
      control bacterial burden. The primary aim of this study was to evaluate the
      clinical improvement in chronic wounds through the effect on wound size,
      maceration, resolution of surface slough and conversion to healthy granulation
      during a 4-week application of the silver-containing Hydrofiber dressing. This
      was a single centre, open-label case series study which included a total of 30
      evaluable participants: four with diabetic neuropathic foot ulcers, 13 venous
      stasis ulcers, four pressure ulcers and nine miscellaneous wounds that did not
      fit any of the previous categories. All participants had adequate vascular
      supply, indicating the potential to heal. The wounds were stalled or had the
      signs and symptoms consistent with critical colonisation. The underlying cause of
      the ulceration was identified and corrected, or the symptoms and signs were
      treated. This was followed by the application of silver-containing Hydrofiber
      dressings for a period of 4 weeks. The majority of wounds treated decreased in
      size (70%) with decreased exudate, decreased purulence and resolution of surface
      slough (75%). There was an increased quality and quantity of healthy granulation
      tissue. Unlike some silver dressings, the Hydrofiber and silver combination
      dressing was unlikely to cause burning and stinging on application. Peri-wound
      maceration was present in 54% of participants at baseline, and 85% of these
      resolved with this dressing. A desloughing action was seen in those patients with
      pre-existing slough at baseline and its removal will lower the bacterial burden
      of the wound.

PMID- 16618323
TI  - Wound chronicity and fibroblast senescence--implications for treatment.
AB  - A proportion of chronic wounds fail to heal in response to standard therapy. For
      venous leg ulcers, a correlation exists between longer duration before treatment
      initiation and poor healing response to compression therapy. Differences
      identified between the healing wound microenvironment and that of the non healing
      chronic wound suggests that many potential mechanisms exist to impair healing.
      One contributory mechanism may be inhibition of fibroblast proliferation and
      induction of a stress-induced premature senescence phenotype by the continuing
      inflammation found in chronic wounds. Senescent fibroblasts exhibit an
      extracellular matrix degradative phenotype that contributes to wound chronicity.
      Accumulation of greater than 15% senescent fibroblasts has been described as a
      threshold beyond which wounds become hard to heal. The ratio of senescent : non
      senescent cells is therefore critical to determining response to treatment, and
      adjunctive therapies that modulate this ratio in favour of non senescent cells
      are likely to enhance therapeutic healing rates. A number of tissue-engineered
      dermal replacements contain non senescent fibroblasts and can donate cells to the
      wound environment additional to releasing growth factors and reversing the
      antiproliferative activity of chronic wound exudate. Recognition of the role of
      fibroblast senescence in wound chronicity may allow for identification of those
      wounds that will respond positively to these products.

PMID- 16618318
TI  - Extending the limits of fingertip composite grafting with moist-exposed dressing.
AB  - We introduced the concept of moist wound healing to extend the limits of
      fingertip composite grafting. In this retrospective study, we assessed the
      success of fingertip composite grafting with moist-exposed ointment dressing,
      which has been shown to maintain adequate moisture for optimal healing by
      frequent ointment application without the need for a secondary overlying
      dressing. We reviewed the outcome of composite graft replacement of 60 amputated
      fingertips in 56 consecutive patients over a period of 3 years and 3 months.
      Forty-two fingertips had survived completely and 18 had failed. Twelve of 15
      fingers among patients younger than 15 years of age and 30 of 45 fingers among
      those 16 years of age and older had survived completely. We believe that our use
      of antibiotic ointment to maintain a moist environment was an important factor in
      improving the survival of composite grafts.

PMID- 16618325
TI  - A general overview of burn care.
AB  - The majority of burn victims do not need to be treated in a burn centre. Adequate
      care can be given by non specialised medical personnel, provided that proper
      guidelines are followed. The article outlines and reviews these guidelines.

PMID- 16618324
TI  - Effects of perioperative hypothermia and warming in surgical practice.
AB  - Perioperative hypothermia is common and adversely affects clinical outcomes due
      to its effect on a range of homeostatic functions. Many of these adverse
      consequences are preventable by the use of warming techniques. A literature
      search was conducted to identify relevant published articles on perioperative
      hypothermia and warming. The databases searched include MEDLINE (1966 to February
      2005), EMBASE (1974 to February 2005), CINAHL, the Cochrane library and the
      health technology assessment database. Reference lists of key articles were also
      searched. The primary beneficial effects of warming are mediated through
      increased blood flow and oxygen tension at tissue level. Reduction in wound
      infection, blood loss and perioperative pain with warming is promising. However,
      more evidence from good-quality prospective randomised controlled trials is
      needed to evaluate the role of warming in improving overall morbidity, mortality
      and hospital stay as well as to clarify its role as an adjunct to resuscitation
      and during the pre-hospital transport phase of critically ill patients. Awareness
      of the risks of perioperative hypothermia is the key to prevention. Achieving
      normothermia throughout the patient's journey is a worthwhile goal in surgical
      patients.

PMID- 16618327
TI  - Telemedicine in wound healing.

PMID- 16618326
TI  - A liquid film-forming acrylate for peri-wound protection: a systematic review and
      meta-analysis (3M Cavilon no-sting barrier film).
AB  - To undertake a systematic review of all reliable evaluations of the clinical
      performance and cost-effectiveness of a film-forming liquid acrylate in the
      protection of the chronic ulcer peri-wound skin. Results from searches were
      scrutinised by two reviewers to identify possible randomised controlled trials
      and full reports of these were obtained. Details of eligible studies were
      extracted and summarised independently by two reviewers using a data extraction
      sheet. Meta-analysis was used to combine the results of trials where the
      interventions and outcome measures were sufficiently similar. A total of nine
      eligible studies were identified. The review reveals that a liquid-film forming
      acrylate (Cavilon no-sting barrier film, 3M, Minneapolis, MN, USA) is a safe and
      effective skin barrier to protect the peri-wound area of chronic ulcers. There is
      no difference between the protective properties of different barrier methods that
      are used to protect the peri-wound skin around chronic ulcers. Compared with no
      treatment or a placebo, this liquid film-forming acrylate has a significant
      impact on the integrity of the peri-wound skin. In addition, it has significant
      benefits in terms of pain control and patient comfort, and its use may reduce
      nursing time.

PMID- 16618328
TI  - Treatment of dystrophic calcification in leg ulcers.

PMID- 16618329
TI  - Use of the sensory nerve stimulator to accelerate healing of a venous leg ulcer
      with sensory nerve dysfunction: a case study.
AB  - A new therapy using sensory nerve stimulation [International Patent Application
      Number PCT/AU2004/001079: "nerve function and tissue healing" (Khalil, Z)] has
      been developed in our vascular physiology laboratory. This treatment has been
      found to improve the deficient sensory nerve function and associated deficient
      wound healing of older persons to levels seen in young people. An 82-year-old man
      with a small but persistent venous leg ulcer for 18 months, despite apparently
      appropriate wound dressings and compression therapy, was seen in a specialist
      wound management service. The patient's sensory and microvascular function was
      assessed in great detail using the vascular physiology laboratory techniques, and
      he was provided the sensory nerve stimulation therapy in addition to conventional
      therapy. His wound healed after 4 weeks. We report the case here. Prior to nerve
      stimulation therapy, cutaneous sensation, microvascular blood flow and oxygen
      tension were found to be reduced near the ulcer when compared with the opposite,
      non ulcerated leg. After therapy, oxygen tension and microvascular blood flow had
      improved. This case provides further evidence that sensory nerve stimulation
      therapy at the stipulated parameters improves wound healing. The observation that
      sensory nerve function improved provides support for the notion that improvement
      in healing is mediated by improved nerve function.

PMID- 16618330
TI  - Wound conditioning of a deep tissue defect including exposed bone after tumour
      excision using PROMOGRAN* Matrix, a protease-modulating matrix.
AB  - A case study reporting on the successful treatment of a patient affected by a
      basal cell carcinoma is submitted. Because the carcinoma had infiltrated deeply,
      a wide excision was necessary, including the removal of bone tissue. The deep
      tissue defect was treated with PROMOGRAN* Matrix, a protease-modulating matrix,
      to promote granulation and ensure that the skin graft do survive and heal
      successfully. In this case study, a rapid development of granulation tissue on
      the exposed surface of the bone was observed. The benefits of the dressing
      enabled a successful split-thickness skin grafting to be carried out which gave
      very good aesthetic and functional results.

PMID- 16618331
TI  - A critical review of irrigation techniques in acute wounds.
AB  - Irrigation is a fundamental concept to the care of acute wounds and therefore of
      prime importance in all surgical specialties. A significant amount of research
      has been done in search of the most effective irrigation technique over the last
      three decades. There is evidence to show that irrigation is beneficial in the
      management of acute traumatic and elective wounds, but exactly which techniques
      and irrigation pressures needed for optimal outcome are still undetermined. A
      significant number of the studies to date lack the rigid scientific design needed
      in a climate of evidence-based medicine. There are substantial methodological
      flaws and a lack of standardisation between many studies hindering the ability to
      draw scientific conclusion and compare different studies. There are few
      randomised, controlled studies on human wounds, and extrapolation from animal
      studies must be done with caution. Investigation into different irrigation
      pressures for different levels of contamination is lacking. This would possibly
      produce a more logical approach for clinically managing acute wounds rather than
      a blanket treatment for all acute wounds irrespective of the level of
      contamination. Further research in this direction with greater attention to
      scientific methodology and design is needed.

PMID- 16618332
TI  - Generalised cutaneous necrosis: a complication of low-molecular-weight heparin.
AB  - Subcutaneous low-molecular-weight heparin (LMWH) injections have a predictable
      dose-dependent anticoagulant effect and have therefore become popular for the
      prevention and management of thromboembolic diseases. It was initially hoped that
      use of the smaller molecule and better dose titration would reduce the incidence
      of side-effects associated with conventional heparin therapy. However, case
      reports such as this have demonstrated that LMWHs still have the capacity to
      cause heparin-induced thrombocytopaenia and heparin-induced thrombocytopaenia
      with thrombosis, as well as heparin necrosis. To our knowledge, this is the first
      ever-reported case of heparin necrosis associated with tinazaparin. Heparin
      necrosis is characterised by widespread life-threatening cutaneous necrosis and
      systemic thrombosis, in which fatal progression of disease can only be halted by
      stopping heparin therapy. As heparin necrosis is an uncommon disorder, in this
      report we focus on the clinical clues that may help woundcare professionals
      consider and confirm the diagnosis.

PMID- 16618333
TI  - Economic comparison of methods of wound closure: wound closure strips vs. sutures
      and wound adhesives.
AB  - Our objective was to review and assess the treatment of low-tension wounds and
      evaluate the cost-effectiveness of wound closure methods. We used a health
      economic model to estimate cost/closure of adhesive wound closure strips, tissue
      adhesives and sutures. The model incorporated cost-driving variables: application
      time, costs and the likelihood and costs of dehiscence and infection. The model
      was populated with variable estimates derived from the literature. Cost estimates
      and cosmetic results were compared. Parameter values were estimated using
      national healthcare and labour statistics. Sensitivity analyses were used to
      verify the results. Our analysis suggests that adhesive wound closure strips had
      the lowest average cost per laceration ($7.54), the lowest cost per infected
      laceration ($53.40) and the lowest cost per laceration with dehiscence ($25.40).
      The costs for sutures were $24.11, $69.91 and $41.91, respectively; the costs for
      tissue adhesives were $28.77, $74.68 and $46.68, respectively. The cosmetic
      outcome for all three treatments was equivalent. We conclude adhesive wound
      closure strips were both a cost-saving and a cost-effective alternative to
      sutures and tissue adhesives in the closure of low-tension lacerations.

PMID- 16618334
TI  - Sleep disruption, daytime somnolence and 'sleep attacks' in Parkinson's disease:
      a clinical survey in PD patients and age-matched healthy volunteers.
AB  - Recent case reports of 'sleep attacks' (SA) in patients with Parkinson's disease
      (PD) generated concerns about drug-induced daytime somnolence in this population.
      However, there are nearly no comparative data on sleep and vigilance problems
      between PD patients and normal controls. We performed a cross-sectional survey in
      PD patients and age-matched controls using a structured questionnaire on PD
      history, treatments, co-morbidity, activities of daily living, habits, exercise,
      sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence,
      episodes of SA and the circumstances in which such episodes occurred. Daytime
      somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep
      quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174
      controls were included. The same proportion of PD patients (27%) and controls
      (32%) reported episodes of SA, but these were more frequent in PD patients and
      occurred more frequently during situations requiring attention (10.8% vs. 1.7%,
      p<10(-3)). More PD patients had abnormal daytime somnolence (ESS) and poor
      sleeping quality (PSQI). The most consistent factor associated with SA was the
      duration of levodopa therapy and the predictive value of an abnormal ESS score
      was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at
      night are more frequent in PD patients than in normals. However, SA are reported
      in both groups, although less frequently in the normals during activities that
      requires attention.

PMID- 16618335
TI  - Migraine and stroke--why do we talk about it?
AB  - Data from observational studies suggest that migraine may be a risk factor for
      stroke. Furthermore, a significant association between migraine and ischemic
      stroke (IS) has been demonstrated in population and case-control studies. The
      risk of IS appears to be higher for migraine with aura than for migraine without
      aura. The pathogenesis is not known but several studies report some common
      biochemical mechanisms in the two diseases. Meta-analysis also demonstrates that
      subjects with migraine are at higher risk of showing white matter abnormalities
      on magnetic resonance images than are those without migraine.

PMID- 16618336
TI  - Eligibility of stroke units in Poland for administration of intravenous
      thrombolysis.
AB  - Systemic thrombolysis treatment was approved in Poland in 2003 and should be
      performed in specialist stroke units (SU). We performed a survey to determine
      stroke service preparedness for thrombolysis treatment in Poland. We sent a
      questionnaire evaluating the neurological departments in Poland, where stroke
      patients are treated. We divided them into four categories: (i) class A SU
      (fulfilling criteria of the National Program for Stroke Prevention and Therapy
      and European Stroke Initiative guidelines), (ii) class B (conditionally
      fulfilling criteria), (iii) class C (not fulfilling criteria), and (iv)
      departments without SU. Only class A units are eligible for implementing
      thrombolysis. We obtained response from 194 of 222 (87.4%) departments; 90
      (46.4%) declared having an SU. According to criteria, 20 class A, 56 class B, 14
      class C. During one year, 71 208 patients were admitted to hospitals; 69,982
      (98.2%) to neurological departments. A total of 10,959 (15.4%) were treated in
      class A SU, 23,650 (33.2%) in class B, 5153 (7.2%) in class C, whereas 30,220
      (42.4%) in neurological departments without SU. Our survey showed that only 15.4%
      stroke patients in Poland are admitted to high-quality SU, where thrombolysis may
      potentially be administered. Improvement of SU quality in Poland is necessary for
      wide implementation of new methods of stroke therapy.

PMID- 16618337
TI  - Emergency department delays in acute stroke - analysis of time between ED arrival
      and imaging.
AB  - We determined the factors leading to emergency department (ED) delays in patients
      with acute stroke. Data were collected prospectively in four Berlin inner-city
      hospitals by ED documentation, medical records, imaging files and patient
      interviews. An extended Cox proportional hazards model was fitted to the data.
      Analyses were performed in 558 patients with confirmed diagnosis of stroke.
      Median time from admission at ED to beginning of computed tomography/magnetic
      resonance imaging (CT/MRI) was 108 min. In a subgroup of patients potentially
      eligible for thrombolysis with a pre-hospital delay <120 min and a National
      Institutes of Health Stroke Scale (NIHSS) >4 (n = 74), the median interval to
      imaging was 68 min. Multivariable analysis revealed that a more severe initial
      NIHSS, a pre-hospital delay <3 h, admission at two specific hospitals, admission
      at weekends, and private health insurance were significantly associated with
      reduced delays. In stroke patients, the time interval between ED admission and
      imaging depends both on factors that emerge from clinical needs and on factors
      independent of clinical necessities. Considering the urgency of therapeutic
      measures in acute stroke, there is necessity and room for both improvement of in
      hospital management and of medical and non-medical factors influencing pre
      hospital delays.

PMID- 16618338
TI  - Neurological complications in AIDS patients receiving HAART: a 2-year
      retrospective study.
AB  - The positive role of highly active anti-retroviral therapy (HAART) in reducing
      opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients is
      well known. However, case reports from around the world have demonstrated that
      some patients seem to suffer a paradoxical deterioration of health as their
      immune function improves with treatment. This phenomenon has been called immune
      restoration inflammatory syndrome (IRIS). In northern Thailand, GPO-vir
      (Stavudine-D4T + Lamivudine-3TC + Nevirapine-NVP) has been promoted for the
      treatment of AIDS patients since April 2002, in accordance with the Government
      Pharmaceutical Organization's guidelines. However, the incidence rates of IRIS
      affecting nervous system (NIRIS) and non-NIRIS in comparison with the previous
      incidence of AIDS-defining disease have not been reported. We conducted a
      retrospective study to review the incidence of NIRIS and non-NIRIS in AIDS
      patients treated with GPO-vir in Chiang Mai University Hospital, Thailand,
      between May 2002 and April 2004. We compare these incidence rates with the
      incidence rates of neurological complications in the pre-HAART era. Altogether
      506 AIDS patients were treated with GPO-vir during the specified period. The
      overall incidence of NIRIS, including progressive multifocal leukoencephalopathy
      (PML), cerebral toxoplasmosis and cytomegalovirus (CMV) retinitis, was lower than
      the previous incidence of AIDS-defining disease in the pre-HAART era. However,
      the incidence of ischemic stroke, hemorrhagic stroke and primary central nervous
      system (CNS) lymphoma had increased.

PMID- 16618339
TI  - Primary intramedullary primitive neuroectodermal tumor (PNET)--case report and
      review of the literature.
AB  - Spinal primitive neuroectodermal tumors (PNET) are very rare tumors, and
      intramedullary localization is even less common. Indeed, amongst the 23 cases of
      the spinal PNET described in the literature, only eight cases had an
      intramedullary localization. Following the WHO 2000 classification, PNETs have
      been considered embryonal tumors composed of undifferentiated neuroepithelial
      cells with a capacity of differentiation into different cellular lines, such as
      astrocytic, ependymal, melanotic and muscular. They have been considered to arise
      from a neoplastic transformation of primitive neuroepithelial cells, thereby
      making their presence possible in any part of the central nervous system. The
      optimal treatment for these malignant tumors is not yet clear, although, over the
      years, radiotherapy has been considered the best treatment for spinal PNETs. The
      described case is that of a 38-year-old man with a primary intra-extramedullary
      PNET, treated by laminectomy, open biopsy and chemotherapy. The patient, 18
      months after the onset of his symptomatology, died without cerebral tumor
      involvement.

PMID- 16618340
TI  - Trigger point evaluation in migraine patients: an indication of peripheral
      sensitization linked to migraine predisposition?
AB  - Although migraine is a neurovascular disorder, both scalp tenderness and referred
      pain have been observed in migraine patients. The present study was carried out
      to investigate the presence of trigger points eliciting referred pain in 98
      migraine patients and in 32 healthy subjects. Trigger points were found in 92
      (93.9%) migraineurs and in nine (29%) controls (P < 0.0001). The number of
      individual migraine trigger points varied from zero to 14 (modal number: 4), and
      was found to be related to both the frequency of migraine attacks (P < 0.0001),
      and the duration of the disease (P = 0.017). About 74% of the total detected
      trigger points were found in temporal and/or suboccipital areas; other locations
      were mainly found in patients showing more than four trigger points. Trigger
      point palpation provoked a migraine attack in 30 (30.6%) patients. Pericraneal
      allodynia was found in 15 (15.3%) patients. These data indicate that nociceptive
      peripheral sensitization is a usual finding in migraine, and that central
      sensitization can develop in patients with frequent attacks and long-lasting
      disease. Trigger points' detection in migraine patients could be useful when
      applying therapies like acupuncture, needling or botulinum toxin injections
      directed to reduce peripheral sensitization.

PMID- 16618341
TI  - Early admission to stroke unit influences clinical outcome.
AB  - An improvement in patient arrival time to stroke unit (SU) is recommended, since
      earlier stroke management seems to improve 'per se' functional outcome. The
      objective of this study was to determine if early admission influences the
      outcome, reduces disability and mortality at discharge and three months later
      independent of tlirombolytic treatment. Consecutive acute stroke patients
      admitted to SU between January 1st 2000 and December 31st 2003 were studied in
      order to analyze the actual role of acute management independent specific
      pharmacological treatment, we excluded subjects who underwent rt-PA. 35.8% of
      2,041 consecutive stroke patients arrived within 3 hours; 62.4% within 6 hours;
      37.6% arrived later. Approximately 80% of the <6 hour patients presented a
      National Institutes of Health Stroke Scale (NIHSS) >4 and modified Rankin Scale
      (mRS) score >2 in comparison with 60% of the >6 hour patients. In hospital (8.7%)
      and three-month (7.3%) mortality in <3 hour patients were not significantly
      different from what observed in >3 hour patients (6.8% and 6.1% respectively)
      while functional outcome after three months was better in <3 hour patients
      (NIHSS: 34.6 vs 15.2; mRS: 32.9% vs 16.8%). Old age, history of TIA,
      cardioembolic etiology, severity of neurological deficit and hemorrhagic stroke
      type all led to earlier arrival time. Admission within 3 hours 'per se' improves
      outcome and reduced disability at three months.

PMID- 16618342
TI  - Spectroscopic evidence of hippocampal abnormalities in neocortical epilepsy.
AB  - Lesional neocortical epilepsy (NE) can be associated with hippocampal sclerosis
      or hippocampal spectroscopic abnormalities without atrophy (dual pathology). In
      this study, magnetic resonance spectroscopic imaging (MRSI) was used to determine
      the frequency of hippocampal damage/dysfunction in NE with and without structural
      lesion. Sixteen patients with NE [seven temporal NE (NE-T), nine extratemporal
      (NE-ET)] and 16 controls were studied with a 2D MRSI sequence (Repetition
      time/echo time (TR/TE) = 1800/135 ms) covering both hippocampi. Seven NE patients
      had MR visible lesions (NE-Les), nine had normal MRI (NE-no). In each
      hippocampus, 12 voxels were uniformly selected. In controls, mean (+/- SD)
      NAA/(Cr + Cho) values for each voxel were calculated and voxels with NAA/(Cr +
      Cho) < or = (mean in controls--2SD in controls) were defined as 'pathological' in
      patients. Eight of 16 NE patients had at least two 'pathological' voxel (mean
      2.5, range 2-5) in one hippocampus. Four were NE-Les and four NE-no. Three (43%)
      NE-T patients, had evidence for hippocampal damage/dysfunction and five (56%) had
      NE-ET. The ipsilateral hippocampus was affected in six of eight NE patients.
      Evidence for unilateral hippocampal damage/dysfunction was demonstrated in 50% of
      the NE patients. The type of NE, i.e. NE-Les or NE-no, NE-T or NE-ET, had no
      influence on the occurrence of hippocampal damage/dysfunction.

PMID- 16618343
TI  - Plasma total homocysteine levels are associated with advanced leukoaraiosis but
      not with asymptomatic microbleeds on T2*-weighted MRI in patients with stroke.
AB  - Both leukoaraiosis and asymptomatic microbleeds are associated with small-artery
      diseases. Although an association between hyperhomocysteinemia and leukoaraiosis
      has been reported, no studies have evaluated the association between total
      homocysteine (tHcy) level and presence of microbleeds in stroke patients. We
      evaluated the association between tHcy level and leukoaraiosis or microbleeds in
      stroke patients. In 102 patients with stroke (69.5 +/- 10.3 years old, 54 men and
      48 women), microbleeds on T2*-weighted MR images were counted, leukoaraiosis on
      T2-weighted images was graded and fasting plasma tHcy concentrations were
      measured. Plasma tHcy level was significantly higher in patients with advanced
      leukoaraiosis than in those without advanced leukoaraiosis (13.9 +/- 4.6
      micromol/l vs. 10.2 +/- 3.4 micromol/l, P < 0.0001). Plasma tHcy level was not
      significantly different in patients with microbleeds and those without
      microbleeds (11.3 +/- 4.1 micromol/l vs. 11.4 +/- 4.3 micromol/l, P = 0.9441).
      Elevated tHcy level is significantly and independently associated with advanced
      leukoaraiosis [odds ratio (OR), 1.330; 95% CI, 1.130-1.565] but not with the
      presence of microbleeds. Elevated tHcy level appears to be associated with
      ischemic small-artery disease rather than with bleeding-prone small-artery
      disease.

PMID- 16618344
TI  - The importance of cerebrospinal fluid on neural cell proliferation in developing
      chick cerebral cortex.
AB  - Cerebrospinal fluid (CSF) is mainly produced by the choroid plexuses within the
      ventricles of the brain. The CSF circulates in a regular manner after the
      ventricular system and the choroids plexuses have developed, and the foramina in
      the fourth ventricle have opened to enable it to carry chemical information. CSF
      flows through the ventricular system passing over all regions of germinal
      activity. In this study, chick embryos were used to show the importance of CSF on
      neural cell proliferation in the developing cerebral cortex. The chick embryos
      were cannulated in situ with a fine capillary tube to drain CSF out of the
      ventricular system. At the same time, BrdU was administered to the embryos. After
      surgery the embryos were incubated for another 3 days. Quantitative measurements
      showed that the thicknesses of the germinal epithelium and cerebral cortex in CSF
      drained embryos were less than those in the control group at the same age. The
      number of cells produced in the germinal epithelium of CSF-drained embryos was
      decreased when compared with the normal group. This study provides confirmatory
      evidence that CSF is important for neural cell proliferation and therefore normal
      development of the cerebral cortex. It is proposed that CSF is vital in
      controlling development of the cerebral cortex.

PMID- 16618345
TI  - Seronegative myasthenia gravis: comparison of neurophysiological picture in MuSK+
      and MuSK- patients.
AB  - The aim of this study was to compare the neurophysiological and clinical pictures
      of a large sample of seronegative myasthenia gravis (SNMG) patients with and
      without anti-MuSK antibodies. Fifty-two consecutive SNMG patients were
      retrospectively evaluated. They had undergone an extended neurophysiological
      evaluation: repetitive nerve stimulation (RNS), single fiber EMG (SFEMG), and
      electromyography (EMG) with nerve conduction study. A muscle biopsy was performed
      in 11 of 52 patients, the edrophonium test in 44 of 52 patients and anti-AChR
      antibodies and anti-MuSK antibodies were tested in all patients. Anti-MuSK
      antibodies were detected in 25 SNMG patients (48.1%). The number of women in the
      MuSK+ group was significantly higher (P = 0.01) than in the MuSK- group.
      Seronegative MuSK+ patients are more severely affected and the deficit often
      involves the bulbar and the respiratory muscles. No statistically significant
      differences were observed in the edrophonium test between MuSK+ and MuSK- groups.
      The RNS test was abnormal in a significantly higher number of MUSK- patients than
      MUSK+ patients (P < 0.00001). With regard to SFEMG data, MuSK- patients were
      characterized to have more severe neurophysiological pattern. Our observations
      showed several differences between the clinical and neurophysiological pictures
      of MUSK+ and MUSK- patients.

PMID- 16618346
TI  - Diagnosing refractory epilepsy: response to sequential treatment schedules.
AB  - Diagnosing refractory epilepsy would facilitate referral for specialist
      pharmacological review and early consideration of epilepsy surgery. An outcomes
      study was undertaken in an unselected cohort of newly diagnosed patients to
      determine the number of antiepileptic drug (AED) regimens needed to be failed
      before the epilepsy could be designated as pharmacoresistant. Between July 1982
      and May 2001, 780 adolescents and adults prescribed their first AED at the
      Western Infirmary in Glasgow, Scotland provided longitudinal data suitable for
      analysis. Overall, 504 (64.6%) patients became seizure free for at least 12
      months. Of these, 462 (59.2%) remained in remission, while 42 (5.4%) relapsed and
      subsequently developed refractory epilepsy. The relapse rate peaked at 10.4%
      after 8 years of follow-up. The other 276 (35.4%) patients were uncontrolled from
      the outset. Prognosis appeared better in seniors (85% remission, P < 0.001) and
      adolescents (65% remission, P < 0.01) than in the remainder of the population
      (55% remission). Overall response rates with the first, second and third
      treatment schedules were 50.4, 10.7 and 2.7%, respectively, with only 0.8%
      patients responding optimally to further drug trials. Patients not tolerating at
      least one AED schedule did better than those failing because of lack of efficacy.
      These data suggest that suitable patients failing two AED regimens should be
      referred for epilepsy surgery. Those who do not attain long-term seizure freedom
      with the first three treatment schedules are likely to have refractory epilepsy.

PMID- 16618347
TI  - The nervous system in early HIV infection: a prospective study through 7 years.
AB  - In this study 28 patients with early stage HIV infection (CD4 >280 x 10(6)/l)
      were subjected to yearly examinations of the nervous system up to 7 years in
      order to detect any deterioration. Clinical neurological as well as
      neuropsychological performance was evaluated. The patients also underwent yearly
      neurophysiological tests (digital EEG, visual evoked potentials, somatosensory
      evoked potentials, auditory evoked potentials P300 and electroneurography). Every
      other year, SPECT with (99m)Tc-D,L-hexamethylpropylene amine oxime and brain MRI
      were performed. Originally, 38 patients were included in the study but only the
      results of 28 patients who complied with three of more yearly check-ups are
      presented. The results of yearly investigations of cerebrospinal fluid (CSF) have
      been presented earlier [Eur J Neurol4 (1997) 1]. All the patients showed signs of
      HIV in the CSF. Yet, no major deterioration in the neurological, psychological
      performance, neurophysiological or neuroimaging examinations could be discerned.

PMID- 16618348
TI  - Granulomatous amebic encephalitis in a multivisceral transplant recipient.
AB  - A 40-year-old man with multivisceral allograft developed acutely right-sided
      numbness 9 months after transplantation. Cranial magnetic resonance imaging (MRI)
      showed a small left parietal lesion, and cerebrospinal fluid analysis was
      unremarkable. Stereotactic brain biopsy was non-diagnostic. The patient continued
      to deteriorate, developed cerebral edema and died at 13 days after the onset of
      symptoms. Unexpectedly, autopsy demonstrated acanthamebic encephalitis. This case
      highlights diagnostic difficulties encountered with amebic encephalitis and
      expands the spectrum of opportunistic central nervous system (CNS) infections in
      solid and visceral organ transplant recipients.

PMID- 16618349
TI  - Proton magnetic resonance spectroscopy of normal appearing white matter in
      asymptomatic relatives of multiple sclerosis patients.
AB  - Proton magnetic resonance spectroscopy of normal appearing white matter (NAWM)
      was performed in 25 first-degree relatives of patients with multiple sclerosis
      (MS). In relatives of MS patients, insignificant trends in the NAA/Cho ratio (to
      be lower) and in the Cho/Cr ratio (to be higher) were found when compared with
      healthy controls. These results demonstrated that there are only minimal,
      insignificant changes in commonly identified metabolite concentrations in NAWM of
      relatives of MS patients when compared with healthy subjects.

PMID- 16618350
TI  - Serum albumin level and nosocomial pneumonia in stroke patients.
AB  - Hypoalbuminemia is associated with increased risk of infections. The aim of this
      study was to determine if serum albumin level is an independent predictor of
      nosocomial pneumonia in stroke patients. Data of 705 consecutive ischemic stroke
      patients admitted within 24 h after stroke onset were analyzed retrospectively.
      Serum albumin level was measured within 36 h after stroke onset. Nosocomial
      pneumonia was found in 10.5% of stroke patients. Patients with pneumonia had
      significantly lower serum albumin level than those without pneumonia (31.9 +/-
      7.5 g/l vs. 35.5 +/- 6.9 g/l) and serum albumin level was associated with risk of
      pneumonia on multivariate analysis (OR: 0.95, 95% CI: 0.91-0.98). Our results
      show that serum albumin level is an independent predictor of nosocomial pneumonia
      in stroke patients.

PMID- 16618351
TI  - Risk of thromboembolism after cerebral venous thrombosis.
AB  - The outcome of cerebral venous thrombosis (CVT) has been studied infrequently. We
      assessed the frequency of recurrence of cerebral or systemic thromboembolism and
      factors influencing recurrence. We performed a retrospective study of consecutive
      patients with CVT in the period 1985-2002 who were admitted to the University
      Hospital Gasthuisberg. We performed a chart review and a semi-standardized
      telephone interview that focused on recurrent CVT or systemic thromboembolism.
      Fifty-four CVT patients with a mean age of 42 years were followed up for a mean
      of 3.5 years. Eighty percent were women. Coagulation disorders were found in 17
      patients (31%). One patient (1.9%) had recurrent CVT and seven patients (12.9%)
      suffered systemic thromboembolism after a median of 2.5 months. Patients with
      recurrent thromboembolism more often had coagulopathies (P = 0.04) or a history
      of deep venous thrombosis (P = 0.007). Patients with early recurrent venous
      thromboembolism often were not treated with oral anticoagulants (P < 0.001). It
      was evident from the above study that a substantial number of patients suffer
      recurrent thromboembolism after CVT.

PMID- 16618352
TI  - Intestinal pseudo-obstruction and neuroleptic malignant syndrome in a chronically
      constipated parkinsonian patient.

PMID- 16618353
TI  - Slow evolution of cerebellar degeneration and chorea in a man with anti-Yo
      antibodies.

PMID- 16618354
TI  - Posterior reversible encephalopathy in eclampsia: diffusion-weighted imaging and
      apparent diffusion coefficient-mapping as prognostic tools?

PMID- 16618355
TI  - Acute Balint's syndrome is not always caused by a stroke.

PMID- 16618358
TI  - Consumption of fish, butter and margarine during pregnancy and development of
      allergic sensitizations in the offspring: role of maternal atopy.
AB  - It has been suggested that changes in dietary habits, particularly increased
      consumption of omega-6 polyunsaturated fatty acids (PUFA) and decreased
      consumption of omega-3 PUFAs may explain the increase in atopic disease seen in
      recent years. Furthermore, it seems possible that it is mainly prenatal or very
      early life environmental factors that influence the development of allergic
      diseases. It has also been suggested that intrauterine risk factors may act
      differently if mother themselves suffer from allergic disease. The aim of this
      study was to investigate whether the consumption of fish, butter and margarine
      during pregnancy might influence the development of allergic sensitizations in
      the offspring. The study population was divided into the offspring of allergic
      and non-allergic mothers. This was a retrospective cohort study enrolling 295
      offspring of allergic mothers and 693 of non-allergic mothers. Information
      regarding maternal intake of fish, butter and margarine during pregnancy as well
      as other prenatal and perinatal confounding factors were retrospectively assessed
      by parental report via a standardized questionnaire. Atopy was determined by skin
      prick tests (SPT) to eight prevalent inhalant allergens and two foods. In the
      allergic mothers' group there is no clear correlation between maternal intakes of
      fish, butter and margarine and sensitizations to food or inhalants. In the non
      allergic mothers' group there was no correlation between butter and margarine
      intake and food or inhalant sensitizations. On the contrary, a protective effect
      of fish intake on SPT positivity was observed. In particular, frequent maternal
      intake ('2-3 times/wk or more') of fish reduced the risk of food sensitizations
      by over a third (aOR 0.23; 95% CI: 0.08-0.69). A similar trend, even if not
      significant, was found for inhalants. Finally, even in the whole study
      population, i.e. allergic group plus non-allergic group, there was a similar
      trend between increased consumption of fish and decreased prevalence of SPT
      positivity for foods. This study shows that frequent intake of fish during
      pregnancy may contrast the development of SPT sensitizations for foods in the
      offspring of mothers without atopic disease. Therefore, larger prospective
      studies are needed, enrolling mothers with and without allergic disease, to
      confirm these results.

PMID- 16618359
TI  - Environmental and dietary risk factors for infantile atopic eczema among a Slovak
      birth cohort.
AB  - Infantile atopic eczema (AE) is a risk marker for future asthma. This study
      assesses the contribution of modifiable exposures to infantile AE. If modifiable
      exposures contribute substantially to infantile AE, its prevention might be a
      sensible approach to asthma prevention. Pregnant women (n = 1978) were
      systematically recruited from maternity hospitals of the Slovak Republic; their
      birthed cohort of 1990 children were prospectively followed for 1 yr. Children's
      exposures to selected environmental and dietary factors were assessed via
      maternal questionnaires administered at delivery and 1 yr of age. A child was
      considered to have AE, based on physical examination (SCORAD index >2) or
      mother's report of a previous physician diagnosis. Multivariate logistic
      regression was used to calculate adjusted odds ratios and percent total
      regression scores (TRS) for each variable. At 1 yr of age 1326 (67%) of the
      children remained in the cohort and 207 (15.6%) developed AE. Various modifiable
      environmental and dietary exposures increased the likelihood of AE (ownership of
      cats; consumption of infant formula, eggs, and fish) while others decreased the
      likelihood of AE (ownership of livestock; exclusive breast feeding for > or =4
      months). Overall, modifiable exposures contributed less to the TRS than did non
      modifiable exposures (38% vs. 62%, respectively). The modifiable exposure
      category that contributed most to the TRS was infant feeding practices (27.5%
      TRS). Modifiable exposures -- especially those related to infant feeding
      practices -- significantly contribute to infantile AE, although modifiable
      factors contribute less overall than do non-modifiable exposures.

PMID- 16618357
TI  - Margarine and butter consumption, eczema and allergic sensitization in children.
      The LISA birth cohort study.
AB  - It has been hypothesized that margarine intake is associated with allergic
      diseases. However, the epidemiological evidence in children is limited. The aim
      of the present study was to assess the relationship between dietary intake of
      margarine and butter with eczema and allergic sensitization in 2-yr-old children.
      Data of 2582 children at the age of 2 yr with complete information on exposure to
      diet and allergic outcome were analyzed in a German prospective birth cohort
      study (LISA). Margarine and butter intake were estimated from a semiquantitative
      food frequency questionnaire about general fat use at home combined with
      questions on the child's spread intake. Multiple logistic regression analysis was
      applied comparing predominant margarine and predominant butter intake with
      consumption of both butter and margarine. Predominant margarine intake was
      positively associated with lifetime prevalence of symptomatic eczema (aOR: 1.71;
      95% CI: 1.12-2.61) and doctor-diagnosed eczema (aOR: 2.10; 95% CI: 1.36-3.25) and
      allergic sensitization against inhalant allergens (aOR: 2.10; 95% CI: 1.01-4.41)
      at the age of 2 yr. No statistically significant associations were found for
      butter intake. Stratification for parental history of atopic diseases indicated
      that children at high risk of atopic diseases have higher effect estimates for
      margarine intake compared to children without parental history of atopic
      diseases. Stratification for sex also showed higher effect estimates in boys.
      Children with predominant margarine consumption had an increased risk for eczema
      and allergic sensitization, while butter intake was no predictor for allergic
      diseases. However, we could not determine whether margarine is a causal risk
      factor or whether other lifestyle factors have influenced this association.

PMID- 16618360
TI  - Impact of early dietary gamma-linolenic acid supplementation on atopic eczema in
      infancy.
AB  - Polyunsaturated fatty acids (PUFAs) are components of cell membranes and may play
      an immunomodulating role in the pathogenesis of atopic dermatitis (AD). The goal
      was to determine the impact of PUFAs on AD by dietary supplementation of infants.
      Based on the parents' decision on their babies' primary feeding, mothers and
      newborns were randomized to the supplementation with gamma-linolenic acid (GLA)
      or placebo for up to 6 months. Breastfed infants received GLA by supplementing
      their mothers. Formula diet was commercial whey hydrolysate unsupplemented with
      PUFAs. Of 131 eligible infants, 24 developed AD within the first year of life. Of
      these, nine belonged to the exclusively breastfed group (n = 58), 14 to the
      combined-fed group (n = 53), and one to the never breastfed group (n = 20). We
      could not find an influence of GLA on the development of AD. In subjects with AD,
      at 1 yr of age the serum-immunoglobulin E (IgE) was the lowest in the GLA
      supplemented group A-subjects. In the GLA-supplemented group, GLA-levels in
      breast milk were similar in atopic and non-atopic infants. In the non
      supplemented group the GLA-content of breast milk was 0.07% of total fatty acids
      in atopic infants vs. 0.17% in non-atopic infants (p < 0.01). Dietary GLA
      supplementation could not prevent AD. Interestingly, the number of infants
      developing AD was the lowest in never breastfed children. In infants suffering
      from AD, GLA-supplementation seemed to reduce total IgE in the first year of
      life.

PMID- 16618361
TI  - The predictive value of early life total immunoglobulin E measurement in
      identifying atopic children in a population-based birth cohort study.
AB  - Atopy is common and the prevalence amongst children is rising. Measurements in
      early childhood that can predict subsequent development of atopy could be
      clinically useful for targeting preventive measures. We used the Children in
      Focus (CiF) subgroup of a large population-based birth cohort study (the Avon
      Longitudinal Study of Parents and Children) to investigate whether total
      immunoglobulin E (IgE) measured at 12 and 18 months could predict subsequent
      development of atopy at 5 yr of age. Atopy was determined by positive skin prick
      test (> or = 3 mm wheal) to one or more of 14 inhalant and food allergens.
      Prevalence of skin prick positivity to any allergen was 14.5% (104 of 715; 95%
      CI: 12.0-17.1%). Total IgE levels were significantly higher at 12 months of age
      (p < 0.0005) but not 18 months of age in those children subsequently atopic. The
      highest positive predictive value was 41% with an IgE measurement of >51 kU/l,
      with a sensitivity of 13.5% and a specificity of 95.8%. Although significant
      differences in early life IgE measurements were seen, the extent of overlap was
      great, such that the overall performance of IgE at 12 months as a screening test
      for atopy was poor.

PMID- 16618362
TI  - Age-related changes in intracellular cytokine profiles and Th2 dominance in
      allergic children.
AB  - The unbalanced T helper response has been pointed out in allergic diseases.
      Especially in childhood, it is important to consider the development of acquired
      immunity. We investigated the relationship between age and Th1, Th2, Tc1 or Tc2
      cells. In addition, Th1, Th2, Tc1 or Tc2 cells in allergic diseases were compared
      with control subjects. Thirty-four healthy controls (0-40 years old), 200 samples
      of cord blood, nine patients with atopic dermatitis (AD) (1-3 years old) and five
      patients with bronchial asthma (BA) (2-6 years old) were studied. Surface
      staining with CD4, CD8 and intracellular staining with anti-interferon-gamma (IFN
      gamma) and anti-interleukin (IL)-4 were carried out, and analyzed by using flow
      cytometry. In the healthy controls, the percentages of Th1, Tc1 or Th2 showed
      positive correlation with age. The absolute numbers of Th1 or Tc1 also correlated
      with age. Cord blood with a family history of allergic disease showed no
      significant difference compared to that without a family history. The percentage
      of Th2 in AD and BA patients was significantly higher than in the age-matched
      healthy controls. The increase in Th1, Th2 and Tc1 with age might reflect on the
      development of acquired immunity. Age matching is important when evaluating the
      cytokine profiles of T cells. In allergic diseases, although cord blood showed a
      Th1-dominant pattern, it changed to Th2 dominance in childhood, and this may
      reflect on some genetic background.

PMID- 16618363
TI  - Faecal SIgA secretion in infants fed on pre- or probiotic infant formula.
AB  - Secretory immunoglobulin A (SIgA) plays an important role in the defence of the
      gastrointestinal tract. The level of faecal SIgA antibody is associated with
      increased neutralization and clearance of viruses. Formula-fed infants who lack
      the transfer of protective maternal SIgA from breast milk may benefit from
      strategies to support maturation of humoral immunity and endogenous production of
      SIgA. We aimed at studying the effects of standard, prebiotic and probiotic
      infant formulas on the faecal SIgA levels. At birth, infants of whom the mother
      had decided not to breastfeed were allocated to one of three formula groups in a
      randomized, double-blind fashion. Nineteen infants received standard infant
      formula; 19 received prebiotic formula containing a specific mixture of 0.6 g
      galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS)/100 ml formula and
      19 received probiotic formula containing 6.0 x 10(9) cfu Bifidobacterium
      animalis/100 ml formula. Faecal samples were taken on postnatal day 5, day 10, wk
      4 and every 4 wk thereafter until wk 32. SIgA in faeces was determined by an
      enzyme-linked immunosorbent assay. During the intervention, infants fed on
      prebiotic formula showed a trend towards higher faecal SIgA levels compared with
      the standard formula-fed infants reaching statistical significance at the age of
      16 wk. In contrast, infants fed on the probiotic formula showed a highly variable
      faecal SIgA concentration with no statistically significant differences compared
      with the standard formula group. Formula-fed infants may benefit from infant
      formulas containing a prebiotic mixture of GOS and FOS because of the observed
      clear tendency to increase faecal SIgA secretion. Adding viable B. animalis
      strain Bb-12 to infant formula did not reveal any sign for such a trend.

PMID- 16618364
TI  - Comparison of fecal microflora in children with atopic eczema/dermatitis syndrome
      according to IgE sensitization to food.
AB  - Atopic eczema/dermatitis syndrome (AEDS) commonly often arises during early
      infancy. In several intervention studies a beneficial influence on AEDS course of
      certain intestinal bacteria, administered as 'probiotics', has been described. To
      evaluate the possible role of the natural intestinal microflora in children with
      allergic eczema/dermatitis syndrome regarding immediate type hypersensitivity to
      food allergens, children with food allergy (AAEDS, n = 68) have been compared
      with children without detectable food allergy (NAEDS, n = 25). All children (n =
      93) in preschool age, mean age of 2.6 (+/-1.8) years, diagnosed with AEDS who
      were treated as inpatients in 2003 in a dermatological hospital were included.
      The correlation between fecal microflora, parasites and specific immunoglobulin E
      (IgE) antibodies against common food allergens was analyzed. A similar
      composition of intestinal microflora in children with AAEDS and NAAEDS was found.
      The food allergens that were most frequently detected were egg white, cow milk,
      casein, peanut and hazelnut. Furthermore, a significant association between IgE
      sensitization against important food allergens and components of the fecal
      microflora could not be demonstrated. With aging changes occur in the intestinal
      microbiota [Proteus/Klebsiella and age (rho = -0.607) and Enterococcus and age
      (rho = -0.428)]. In two subjects of the AAEDS group Blastocystis hominis was
      found. The composition of natural intestinal microflora in children with AAEDS
      and NAAEDS was similar. Hence, there is no evidence of a role of the intestinal
      microflora with regard to the development of infant (food) allergy in children
      with AEDS. The possible consequences for allergic diseases later in life require
      further investigation.

PMID- 16618365
TI  - Basophil Activation Test and specific IgE measurements using a panel of
      recombinant natural rubber latex allergens to determine the latex allergen
      sensitization profile in children.
AB  - There are no documented studies that describe natural rubber latex (NRL)
      sensitization in children with a history of surgical intervention but without any
      congenital malformation (urogenital anomalies, spina bifida, etc.), although some
      authors have studied NRL allergy in children without a history of surgical
      intervention. The aim of this work was to evaluate the sensitization profile to
      single NRL allergens in children without spina bifida and without repeated
      surgical interventions, by using different recombinant and natural latex
      allergens in two analytical techniques: specific serum immunoglobulin E (IgE)
      quantification and flow cytometry determination of activated basophils expressing
      CD63, after stimulating cells from patients with NRL allergens. A total of 23
      patients and 10 healthy children were selected. Conjunctival and in-use NRL
      provocation tests were carried out, as well as specific IgE determination in all
      patients' and controls' sera with the recombinant NRL allergens: rHev b 1, rHev b
      2, rHev b 3, rHev b 5, rHev b 6.01, rHev b 6.02, rHev b 8, rHev b 9 and rHev b 11
      and with NRL (k82) using appropriate ImmunoCAPs. The Basophil Activation Test
      (BAT) was performed with whole latex extract and with the recombinant allergens
      rHev b 5 and rHev b 6.01, as well as with the natural allergen Hev b 6.02. The
      sensitivity and the specificity of NRL-specific IgE (k82) were 100%. Positive IgE
      responses to rHev b 5 were found in sera of 10 children, to rHev b 6.01 in 16 and
      for rHev b 6.02 in 15 children's sera. Specific IgE to rHev b 8 was found in four
      sera of the children. We only found significant differences in sensitization to
      rHev b 5 in children with two or more surgical interventions compared with the
      non-intervened group or those with only one intervention. Specific IgE in sera of
      children with latex-fruit syndrome recognized rHev b 6.02, but not to rHev b 11.
      The patients sensitized to Hev b 8, Hev b 9 and/or Hev b 11 were atopic. The four
      patients presenting a positive response to the NRL profilin Hev b 8 were allergic
      to pollen. The BAT against whole NRL extract was positive in 22 of 23 children;
      against rHev b 5 in 14 of the patients studied; against rHev b 6.01 in seven
      cases and against nHev b 6.02 in 19 children. In all the control subjects, the
      results using this technique were negative. If combined rHev b 5, rHev b 6.01 and
      nHev b 6.02 together, BAT could detect 20 of the 23 children with latex allergy.
      The combined use of ImmunoCAP with all the recombinant NRL allergens and BAT with
      rHev b 5, rHev b 6.01 and nHev b 6.02, enabled the identification of NRL allergy
      in 22 of 23 patients. There is a positive and significant correlation between
      sensitization to Hev b 5 and the number of interventions. BAT and allergen
      specific IgE determination could be used as first-line in vitro diagnostic tests
      in patients with NRL allergy.

PMID- 16618366
TI  - The difficulties of diagnosing food-dependent exercise-induced anaphylaxis in
      childhood -- a case study and review.
AB  - We describe a case report of peanut and hens egg-dependent exercise-induced
      anaphylaxis in a 13-yr-old child, and assess the fundamental importance of
      careful investigations to differentiate food-dependent exercise-induced
      anaphylaxis from other forms of allergic reactions.

PMID- 16618367
TI  - Interleukin-8 response and respiratory mucosal inflammation.

PMID- 16618368
TI  - Length-dependent prediction of protein intrinsic disorder.
AB  - BACKGROUND: Due to the functional importance of intrinsically disordered proteins
      or protein regions, prediction of intrinsic protein disorder from amino acid
      sequence has become an area of active research as witnessed in the 6th experiment
      on Critical Assessment of Techniques for Protein Structure Prediction (CASP6).
      Since the initial work by Romero et al. (Identifying disordered regions in
      proteins from amino acid sequences, IEEE Int. Conf. Neural Netw., 1997), our
      group has developed several predictors optimized for long disordered regions (>30
      residues) with prediction accuracy exceeding 85%. However, these predictors are
      less successful on short disordered regions (< or =30 residues). A probable cause
      is a length-dependent amino acid compositions and sequence properties of
      disordered regions. RESULTS: We proposed two new predictor models, VSL2-M1 and
      VSL2-M2, to address this length-dependency problem in prediction of intrinsic
      protein disorder. These two predictors are similar to the original VSL1 predictor
      used in the CASP6 experiment. In both models, two specialized predictors were
      first built and optimized for short (< or = 30 residues) and long disordered
      regions (>30 residues), respectively. A meta predictor was then trained to
      integrate the specialized predictors into the final predictor model. As the 10
      fold cross-validation results showed, the VSL2 predictors achieved well-balanced
      prediction accuracies of 81% on both short and long disordered regions.
      Comparisons over the VSL2 training dataset via 10-fold cross-validation and a
      blind-test set of unrelated recent PDB chains indicated that VSL2 predictors were
      significantly more accurate than several existing predictors of intrinsic protein
      disorder. CONCLUSION: The VSL2 predictors are applicable to disordered regions of
      any length and can accurately identify the short disordered regions that are
      often misclassified by our previous disorder predictors. The success of the VSL2
      predictors further confirmed the previously observed differences in amino acid
      compositions and sequence properties between short and long disordered regions,
      and justified our approaches for modelling short and long disordered regions
      separately. The VSL2 predictors are freely accessible for non-commercial use at
      http://www.ist.temple.edu/disprot/predictorVSL2.php.

PMID- 16618369
TI  - Allele frequency misspecification: effect on power and Type I error of model
      dependent linkage analysis of quantitative traits under random ascertainment.
AB  - BACKGROUND: Studies of model-based linkage analysis show that trait or marker
      model misspecification leads to decreasing power or increasing Type I error rate.
      An increase in Type I error rate is seen when marker related parameters (e.g.,
      allele frequencies) are misspecified and ascertainment is through the trait, but
      lod-score methods are expected to be robust when ascertainment is random (as is
      often the case in linkage studies of quantitative traits). In previous studies,
      the power of lod-score linkage analysis using the "correct" generating model for
      the trait was found to increase when the marker allele frequencies were
      misspecified and parental data were missing. An investigation of Type I error
      rates, conducted in the absence of parental genotype data and with
      misspecification of marker allele frequencies, showed that an inflation in Type I
      error rate was the cause of at least part of this apparent increased power. To
      investigate whether the observed inflation in Type I error rate in model-based
      LOD score linkage was due to sampling variation, the trait model was estimated
      from each sample using REGCHUNT, an automated segregation analysis program used
      to fit models by maximum likelihood using many different sets of initial
      parameter estimates. RESULTS: The Type I error rates observed using the trait
      models generated by REGCHUNT were usually closer to the nominal levels than those
      obtained when assuming the generating trait model. CONCLUSION: This suggests that
      the observed inflation of Type I error upon misspecification of marker allele
      frequencies is at least partially due to sampling variation. Thus, with missing
      parental genotype data, lod-score linkage is not as robust to misspecification of
      marker allele frequencies as has been commonly thought.

PMID- 16618370
TI  - Household and community socioeconomic and environmental determinants of child
      nutritional status in Cameroon.
AB  - BACKGROUND: Undernutrition is a leading cause of child mortality in developing
      countries, especially in sub-Saharan Africa. We examine the household and
      community level socioeconomic and environmental factors associated with child
      nutritional status in Cameroon, and changes in the effects of these factors
      during the 1990s economic crisis. We further consider age-specific effects of
      household economic status on child nutrition. METHODS: Child nutritional status
      was measured by weight-for-age (WAZ) and height-for-age (HAZ) z-scores. Data were
      from Demographic and Health Surveys conducted in 1991 and 1998. We used analysis
      of variance to assess the bivariate association between the explanatory factors
      and nutritional status. Multivariate, multilevel analyses were undertaken to
      estimate the net effects of both household and community factors. RESULTS:
      Average WAZ and HAZ declined respectively from -0.70 standard deviations (SD),
      i.e. 0.70 SD below the reference median, to -0.83 SD (p = 0.006) and from -1.03
      SD to -1.14 SD (p = 0.026) between 1991 and 1998. These declines occurred mostly
      among boys, children over 12 months of age, and those of low socioeconomic
      status. Maternal education and maternal health seeking behavior were associated
      with better child nutrition. Household economic status had an overall positive
      effect that increased during the crisis, but it had little effect in children
      under 6 months of age. Improved household (water, sanitation and cooking fuel)
      and community environment had positive effects. Children living in the driest
      regions of the country were consistently worst off, and those in the largest
      cities were best off. CONCLUSION: Both household and community factors have
      significant impact on child health in Cameroon. Understanding these relationships
      can facilitate design of age- and community-specific intervention programs.

PMID- 16618372
TI  - Risk factors for pre-term birth in Iraq: a case-control study.
AB  - BACKGROUND: Preterm birth (PTB)is a major clinical problem associated with
      perinatal mortality and morbidity. The aim of the present study is to identify
      risk factors associated with PTB in Mosul, Iraq. METHODS: A case-control study
      was conducted in Mosul, Iraq, from 1st September, 2003 to 28th February, 2004.
      RESULTS: A total of 200 cases of PTB and 200 controls of full-term births were
      screened and enrolled in the study. Forward logistic regression analysis was used
      in the analysis. Several significant risk associations between PTB and the
      following risk factors were identified: poor diet (OR = 4.33), heavy manual work
      (OR = 1.70), caring for domestic animals (OR = 5.06), urinary tract infection (OR
      = 2.85), anxiety (OR = 2.16), cervical incompetence (OR = 4.74), multiple
      pregnancies (OR = 7.51), direct trauma to abdomen (OR = 3.76) and abortion (OR =
      6.36). CONCLUSION: The main determinants of PTB in Iraq were low socio-economic
      status and factors associated with it, such as heavy manual work and caring for
      domestic animals, in addition to urinary tract infections and poor obstetric
      history.

PMID- 16618371
TI  - Analysis of 10,000 ESTs from lymphocytes of the cynomolgus monkey to improve our
      understanding of its immune system.
AB  - BACKGROUND: The cynomolgus monkey (Macaca fascicularis) is one of the most widely
      used surrogate animal models for an increasing number of human diseases and
      vaccines, especially immune-system-related ones. Towards a better understanding
      of the gene expression background upon its immunogenetics, we constructed a cDNA
      library from Epstein-Barr virus (EBV)-transformed B lymphocytes of a cynomolgus
      monkey and sequenced 10,000 randomly picked clones. RESULTS: After processing,
      8,312 high-quality expressed sequence tags (ESTs) were generated and assembled
      into 3,728 unigenes. Annotations of these uniquely expressed transcripts
      demonstrated that out of the 2,524 open reading frame (ORF) positive unigenes
      (mitochondrial and ribosomal sequences were not included), 98.8% shared
      significant similarities (E-value less than 1e-10) with the NCBI nucleotide (nt)
      database, while only 67.7% (E-value less than 1e-5) did so with the NCBI non
      redundant protein (nr) database. Further analysis revealed that 90.0% of the
      unigenes that shared no similarities to the nr database could be assigned to
      human chromosomes, in which 75 did not match significantly to any cynomolgus
      monkey and human ESTs. The mapping regions to known human genes on the human
      genome were described in detail. The protein family and domain analysis revealed
      that the first, second and fourth of the most abundantly expressed protein
      families were all assigned to immunoglobulin and major histocompatibility complex
      (MHC)-related proteins. The expression profiles of these genes were compared with
      that of homologous genes in human blood, lymph nodes and a RAMOS cell line, which
      demonstrated expression changes after transformation with EBV. The degree of
      sequence similarity of the MHC class I and II genes to the human reference
      sequences was evaluated. The results indicated that class I molecules showed weak
      amino acid identities (<90%), while class II showed slightly higher ones.
      CONCLUSION: These results indicated that the genes expressed in the cynomolgus
      monkey could be used to identify novel protein-coding genes and revise those
      incomplete or incorrect annotations in the human genome by comparative methods,
      since the old world monkeys and humans share high similarities at the molecular
      level, especially within coding regions. The identification of multiple genes
      involved in the immune response, their sequence variations to the human
      homologues, and their responses to EBV infection could provide useful information
      to improve our understanding of the cynomolgus monkey immune system.

PMID- 16618374
TI  - Severity of self-reported diseases and symptoms in Denmark.
AB  - OBJECTIVE: To estimate and rank the relative severity of self-reported diseases
      and symptoms in Denmark. METHOD: The 1994 Danish Health and Morbidity Survey
      collected data from 5,472 Danes older than 16 years of age. Interviews (response
      frequency: 79%) gave information on diseases and symptoms; a self-administered SF
      36 questionnaire (response frequency: 64%) provided information on health-related
      quality of life. The severity of diseases and symptoms was represented by the
      health-related quality of life scores that individuals suffering from particular
      diseases and symptoms obtained on the single dimensions of the SF-36 and on a
      combined sum of all dimensions. We applied logistic regression to control for the
      influence of sex, age and socio-economic status on the SF-36 score. We also
      analysed the interaction between socio-economic status and diseases on the SF-36
      score. RESULTS: Females, more frequently than males, reported on all symptoms and
      all disease groups except injuries. People with relatively low levels of
      education reported most diseases, especially musculoskeletal and cardiovascular
      diseases, more frequently than people with higher education. Age-adjusted mean SF
      36 scores for all dimensions combined showed that the symptoms of
      melancholy/depression and breathing difficulties, psychiatric disorders and
      respiratory diseases scored lowest (i.e. were most often associated with worse
      health). Females had lower SF-36 combined scores (worse health) than males on all
      symptoms. We found interaction between socio-economic status and respiratory
      diseases and musculoskeletal diseases on the SF-36 score. SF-36 scores also
      indicated significantly worse health among Danes with low education and income
      levels compared to those with higher education and income. CONCLUSION: In 1994
      the Danes most frequently reported musculoskeletal symptoms and diseases.
      Psychiatric disorders and respiratory diseases were identified as the most severe
      reported diseases. Due to the interaction between socio-economic status and some
      diseases, severity estimates should be interpreted with caution or stratified by
      socio-economic groups.

PMID- 16618373
TI  - Early lens aging is accelerated in subjects with a high risk of ischemic heart
      disease: an epidemiologic study.
AB  - BACKGROUND: Ischemic heart disease (IHD) is one of the most important causes of
      mortality and morbidity in the Western world. There is a relationship between
      aging of the lens of the human eye and cardiovascular disease. The present study
      was conducted to examine if the risk of ischemic heart disease could be estimated
      by fluorophotometric assessment of lens aging. METHODS: A total of 421 subjects
      were included. Risk of IHD was estimated from non-ocular data using the Precard
      software. Lens aging was quantified by lens fluorometry. RESULTS: The risk of IHD
      was strongly related to lens fluorophore accumulation (p = 0.001). The
      relationship between IHD and lens aging was attributable to tobacco smoking and
      dysglycemia. CONCLUSION: The risk of ischemic heart disease related to smoking
      and diabetes mellitus can be estimated using the aging of the lens of the eye as
      a biomarker for generalized tissue-damage.

PMID- 16618375
TI  - Music therapy in moderate and severe dementia of Alzheimer's type: a case-control
      study.
AB  - BACKGROUND: Music therapy is a potential non-pharmacological treatment for the
      behavioral and psychological symptoms of dementia, but although some studies have
      found it to be helpful, most are small and uncontrolled. METHODS: This case
      control study was carried out by qualified music therapists in two nursing homes
      and two psychogeriatric wards. The participants were 38 patients with moderate or
      severe Alzheimer's disease (AD) assigned randomly to a music therapy group and a
      control group. RESULTS: The study showed a significant reduction in activity
      disturbances in the music therapy group during a 6-week period measured with the
      Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). There was
      also a significant reduction in the sum of scores of activity disturbances,
      aggressiveness and anxiety. Other symptoms rated by subscales of the BEHAVE-AD
      did not decrease significantly. Four weeks later the effects had mostly
      disappeared. CONCLUSIONS: Music therapy is a safe and effective method for
      treating agitation and anxiety in moderately severe and severe AD. This is in
      line with the results of some non-controlled studies on music therapy in
      dementia.

PMID- 16618377
TI  - Consistency of couple declaration about using family planning methods in Turkey.
AB  - The aim of this study was to determine the consistency of spouses' declarations
      about contraceptive use and child desire in Turkey. Husbands eligible for the
      study were currently married to eligible women, i.e. those who generally lived in
      the same household or who stayed in the household the night before the interview.
      Husband questionnaires were completed by 1971 men. It was found that 88.9% of the
      couples had not talked about family planning with each other in the last two
      months. The percentage of answers on current contraceptive use for all methods
      that were consistent for husbands and wives was 70.2%. The consistency among
      partners who stated they would like to have children in the future was found to
      be 94.8%, and that among partners who were planning to use a contraceptive method
      was found to be 88.3%.

PMID- 16618376
TI  - Masculinity-femininity predicts sexual orientation in men but not in women.
AB  - Using the nationally representative sample of about 15,000 Add Health respondents
      in Wave III, the hypothesis is tested that masculinity-femininity in adolescence
      is correlated with sexual orientation 5 years later and 6 years later: that is,
      that for adolescent males in 1995 and again in 1996, more feminine males have a
      higher probability of self-identifying as homosexuals in 2001-02. It is predicted
      that for adolescent females in 1995 and 1996, more masculine females have a
      higher probability of self-identifying as homosexuals in 2001-02. Masculinity
      femininity is measured by the classical method used by Terman & Miles. For both
      time periods, the hypothesis was strongly confirmed for males: the more feminine
      males had several times the probability of being attracted to same-sex partners,
      several times the probability of having same-sex partners, and several times the
      probability of self-identifying as homosexuals, compared with more masculine
      males. For females, no relationship was found at either time period between
      masculinity and sex of preference. The biological mechanism underlying
      homosexuality may be different for males and females.

PMID- 16618378
TI  - Association of household demographic variables with child mortality in Cote
      d'Ivoire.
AB  - The associations between household demographic variables and mortality of
      children aged less than five years were investigated using data from the 1998
      Demographic and Health Survey (DHS) of the Republic of Cote d'Ivoire, Western
      Africa. Of the total of 1992 children born to women included in the study
      population during the 5-year period preceding the survey, 260 (13%) had died and
      1732 (87%) were alive at the time of the survey. Logistic regression analyses
      used to compare biosocial variables between the deceased and living children
      showed that the sex of the child, birth interval and mother's occupation were
      associated with child's survival status. After adjusting for their effects,
      household demographic variables (i.e. number of household members, number of
      household members under 5 years [HM-5Y], number of household members 5 years or
      older [HM+5Y], the proportion of HM-5Y among all household members, and the ratio
      of HM-5Y to HM+5Y) were shown to be associated with the child's survival status.
      This study provided insight into the effects of intra-household competition among
      children and availability of care-givers as potential determinants of child
      survival. The results indicate that improvement of the childcare environment and
      reproductive intervention are necessary to reduce child mortality in West African
      countries.

PMID- 16618379
TI  - Adjuvant therapy for colon cancer.
AB  - Colon cancer is a leading cause of cancer and cancer deaths in Western countries.
      Although 5-fluorouracil is still the basis of adjuvant therapy, advances in drug
      development have led to increased efficacy with the addition of oxaliplatin and
      options for oral therapy with capecitabine. The benefit of adjuvant therapy for
      stage II disease is consistently small and not statistically significant. Future
      studies will evaluate the role of the biologic agents that have proved to be
      effective in metastatic disease and better delineate the population at risk by
      identifying prognostic and predictive markers.

PMID- 16618380
TI  - Preoperative and adjuvant treatment of localized rectal cancer.
AB  - Although postoperative chemoradiation has a proven role in the treatment of stage
      II to III localized rectal cancer, recent trials have demonstrated the role of
      preoperative chemoradiation. A recent randomized trial has shown that
      preoperative chemoradiation yields higher rates of local control and sphincter
      preservation and lower rates of toxicity, compared with postoperative
      chemoradiation. Randomized trials have also shown that preoperative
      chemoradiation yields higher rates of pathologic complete response and local
      control, compared with radiotherapy alone. In this article, we review recent
      trials on preoperative and adjuvant therapy of localized rectal cancer. The roles
      of newer agents, such as capecitabine, oxaliplatin, and bevacizumab, are also
      discussed, and other key issues in the treatment of localized rectal cancer are
      reviewed.

PMID- 16618381
TI  - Multimodality treatment of esophageal cancer: a review of the current status and
      future directions.
AB  - Surgical resection will cure only 15% to 20% of patients with seemingly localized
      esophageal cancer. Multimodality therapy has the potential to increase the cure
      rate by improving locoregional control and preventing systemic relapse.
      Randomized trials demonstrate that chemoradiation followed by surgery decreases
      local relapse as compared with surgery alone; however, the effect on overall
      survival remains uncertain. The additional impact of surgery following
      chemoradiation also remains unclear, with two randomized trials demonstrating an
      improvement in locoregional control without a benefit in survival. Morbidity and
      mortality of trimodality therapy have limited potential gains. Incorporation of
      docetaxel, irinotecan, and oxaliplatin into chemotherapy regimens prior to
      chemoradiation or as adjuvant therapy may decrease systemic recurrence. New
      radiation sensitizers may improve locoregional control. Biologic agents, such as
      cetuximab, trastuzumab, erlotinib, and bevacizumab, may enhance chemoradiation
      and target systemic micrometastases. Advances in radiation oncology and surgery
      may decrease morbidity and mortality from trimodality therapy, improving patient
      outcome.

PMID- 16618382
TI  - Gastric cancer: an update.
AB  - Gastric cancer is an aggressive malignancy, which, if metastatic or unresectable,
      is incurable. However, with metastatic or unresectable disease, patients receive
      a palliative benefit from chemotherapy. Although the understanding of the biology
      of this disease is increasing, the development of biologically targeted therapies
      for gastric cancer has been limited. Cytotoxic therapy remains the standard
      approach, and although there is agreement on the active agents and active
      combination chemotherapy regimens, consensus on the standard or reference regimen
      is lacking. This article reviews the pathophysiology of this disease, placing it
      in the context of its epidemiology, and the current advances in the treatment of
      this disease.

PMID- 16618383
TI  - Imatinib-refractory gastrointestinal stromal tumors: the clinical problem and
      therapeutic strategies.
AB  - Treatment of gastrointestinal stromal tumor (GIST) is a paradigm for targeted
      therapy. These mesenchymal tumors are refractory to standard chemotherapy and
      radiation therapy. Targeted therapy has successfully exploited the oncologic
      drivers of GIST--the tyrosine kinases, KIT, and the platelet-derived growth
      factor receptor. Therapy with imatinib has dramatically altered the natural
      history of patients with advanced GIST. However, patients are developing
      resistance to imatinib and thus presenting with a major clinical challenge.
      Alternative approaches to imatinib-refractory disease are needed. Newer
      approaches using biologic data regarding the mechanisms of resistance are being
      tested alone or in combination with imatinib and are the focus of this review.
      Effective novel agents for imatinib-refractory GIST used as single agents or in
      combination with imatinib will likely become future regimens to be tested in
      first-line metastatic disease and in the adjuvant setting.

PMID- 16618384
TI  - New treatments for superficial bladder cancer.
AB  - The successful treatment of bladder cancer remains a challenge for urologists and
      oncologists. Substantial changes have been made in the therapeutic options for
      the management of superficial bladder cancer in the past 5 years. We review the
      preclinical and clinical developments over the past year in bladder cancer
      therapeutics. A growing trend involves the use of multimodality treatments for
      all bladder cancers. For superficial disease, intravesical instillation of
      chemotherapeutic agents after transurethral resection is quickly becoming the
      standard of care. Novel therapeutic modalities under investigation include DNA
      vaccines, magnetically targeted carriers, bioadhesive microspheres, and antisense
      oligodeoxynucleotides. Treatment goals for superficial bladder cancer are
      complete removal of the initial tumor, prevention of disease recurrence, and
      inhibition of progression to invasive disease. The myriad novel therapeutic
      modalities under exploration suggest that these goals may be achievable within
      our lifetime.

PMID- 16618385
TI  - Targeted approaches for the management of metastatic prostate cancer.
AB  - Huggins and Hodges described the first systemic targeted therapy for prostate
      cancer in 1941 with their report on the effects of androgen ablation in men with
      metastatic disease. Since that time, researchers have identified multiple
      additional "targets" that may be important in prostate cancer tumorigenesis.
      These areas include continued emphasis on the androgen receptor in the androgen
      independent state, parallel growth pathways such as AKT and HER2 that may act in
      conjunction or independently of the androgen receptor, the supporting environment
      that allows for the development of metastatic disease, and standard cytotoxic
      targets, such as the microtubule. This review is intended to highlight these
      potential targets and several of the agents that are under development in the
      treatment of prostate cancer.

PMID- 16618386
TI  - Management of asymptomatic rise in prostatic-specific antigen in patients with
      prostate cancer.
AB  - Biochemical failure after curative-intent therapies is an increasingly common
      dilemma confronting patients and physicians. No definition of biochemical failure
      exists that can be applied to all forms of treatment and that is not to some
      degree affected by the follow-up interval, pretreatment prognostic factors, or
      the frequency of prostatic-specific antigen (PSA) testing. Available imaging
      techniques lack sensitivity in detection of occult micrometastases. Prognostic
      factors such as tumor characteristics and PSA kinetics should be considered when
      recommending second-line therapies. For those patients with suspected localized
      recurrence, second-line treatment with salvage therapies may provide long-term
      disease control. Hormonal therapy, although most commonly employed for PSA
      recurrence, is of palliative benefit only. Currently, the most appropriate
      therapeutic intervention for asymptomatic patients with evidence of biochemical
      failure remains undefined.

PMID- 16618387
TI  - The role of bisphosphonates in the management of prostate cancer.
AB  - Current therapies have extended the survival of patients with prostate cancer.
      However, these patients often develop skeletal morbidity from disease- and
      treatment-related effects that undermine skeletal integrity throughout the course
      of the disease. Low bone mineral density (BMD) is prevalent in patients with
      early-stage prostate cancer, and androgen-deprivation therapy by either
      pharmaceutical agent (including hormonal) or surgical castration causes
      significant decreases in BMD. Fractures can result in a loss of independence and
      have been associated with shorter survival in patients with prostate cancer.
      Zoledronic acid is the only bisphosphonate that has demonstrated objective and
      long-term benefits in reducing skeletal morbidity in patients with bone
      metastases due to prostate cancer, and it has produced long-term reductions in
      pain levels compared with placebo in this setting. Therefore, bisphosphonates,
      particularly zoledronic acid, may provide important benefits for preserving bone
      health during the course of prostate cancer progression.

PMID- 16618388
TI  - The use of herbal and over-the-counter dietary supplements for the prevention of
      prostate cancer.
AB  - Having a high probability of experiencing prostate cancer during their lifetime,
      men are increasingly seeking protection against this disease with the use of over
      the-counter dietary supplements containing herbs, vitamins, or plant-derived
      biochemical agents. The use of these agents for prostate cancer prevention is
      driven by epidemiology supporting the idea that regional diets and consumption of
      specific dietary components (certain herbs, vitamins, isoflavones, and
      polyphenols) are associated with a lower risk for prostate cancer, in conjunction
      with basic research that is defining molecules within food substances that kill
      or suppress growth of cultured human prostate cancer cells. Moreover, there is a
      sense that these dietary agents lack side effects, although this assumption often
      is faulty. Unfortunately, at this time, there is insufficient clinical evidence
      to support the widespread use of these dietary supplements for chemoprevention of
      prostate cancer, although ongoing clinical trials of the most promising vitamins
      and minerals are approaching conclusion.

PMID- 16618395
TI  - Cybermedicine and the gastroenterologist.

PMID- 16618389
TI  - Hepatocyte nuclear factor 4alpha is essential for embryonic development of the
      mouse colon.
AB  - BACKGROUND & AIMS: Hepatocyte nuclear factor 4 alpha (HNF4alpha) is a
      transcription factor that has been shown to be required for hepatocyte
      differentiation and development of the liver. It has also been implicated in
      regulating expression of genes that act in the epithelium of the lower
      gastrointestinal tract. This implied that HNF4alpha might be required for
      development of the gut. METHODS: Mouse embryos were generated in which Hnf4a was
      ablated in the epithelial cells of the fetal colon by using Cre-loxP technology.
      Embryos were examined by using a combination of histology, immunohistochemistry,
      DNA microarray, reverse-transcription polymerase chain reaction, electrophoretic
      mobility shift assays, and chromatin immunoprecipitation analyses to define the
      consequences of loss of HNF4alpha on colon development. RESULTS: Embryos were
      recovered at E18.5 that lacked HNF4alpha in their colons. Although early stages
      of colonic development occurred, HNF4alpha-null colons failed to form normal
      crypts. In addition, goblet-cell maturation was perturbed and expression of an
      array of genes that encode proteins with diverse roles in colon function was
      disrupted. Several genes whose expression in the colon was dependent on HNF4alpha
      contained HNF4alpha-binding sites within putative transcriptional regulatory
      regions and a subset of these sites were occupied by HNF4alpha in vivo.
      CONCLUSIONS: HNF4alpha is a transcription factor that is essential for
      development of the mammalian colon, regulates goblet-cell maturation, and is
      required for expression of genes that control normal colon function and
      epithelial cell differentiation.

PMID- 16618396
TI  - Thirty-year analysis of a colonoscopic surveillance program for neoplasia in
      ulcerative colitis.
AB  - BACKGROUND & AIMS: The value of colonoscopic surveillance for neoplasia in long
      standing extensive ulcerative colitis remains controversial. This study reports
      on prospectively collected data from a surveillance program over a 30-year
      period. METHODS: Data were obtained from the prospective surveillance database,
      medical records, colonoscopy, and histology reports. The primary end point was
      defined as death, colectomy, withdrawal from surveillance, or census date
      (January 1, 2001). Follow-up information was obtained for patients who left the
      program. RESULTS: Six hundred patients underwent 2627 colonoscopies during 5932
      patient-years of follow-up. The cecal intubation rate was 98.7%, with no
      significant complications. Seventy-four patients (12.3%) developed neoplasia,
      including 30 colorectal cancers (CRCs). There was no difference in median age at
      onset of colitis for those with or without CRC (P = .8, Mann-Whitney). The
      cumulative incidence of CRC by colitis duration was 2.5% at 20 years, 7.6% at 30
      years, and 10.8% at 40 years. The 5-year survival rate was 73.3%. Sixteen of 30
      cancers were interval cancers. CRC incidence decreased over time (r = -.40, P =
      .04; linear regression). CONCLUSIONS: Colonoscopic surveillance is safe and
      allows the vast majority of patients to retain their colon. Although two thirds
      of patients with potentially life-threatening neoplasia benefited from
      surveillance, the program was not wholly effective in cancer prevention. The
      cancer incidence, however, was considerably lower than in the majority of other
      studies, and was constant for up to 40 years of colitis duration, suggesting
      there is no need to intensify surveillance over time.

PMID- 16618397
TI  - Risk of intestinal cancer in inflammatory bowel disease: a population-based study
      from olmsted county, Minnesota.
AB  - BACKGROUND & AIMS: The risk for colorectal cancer in Crohn's disease and
      ulcerative colitis patients from the United States currently is unknown. We
      estimated the risk for small-bowel and colorectal cancer in a population-based
      cohort of 692 inflammatory bowel disease patients from Olmsted County, Minnesota,
      from 1940 to 2001. METHODS: The Rochester Epidemiology Project was used to
      identify cohort patients with colorectal and small-bowel cancer. The cumulative
      probability of cancer and standardized incidence ratios (SIR) were estimated
      using expected rates from Surveillance, Epidemiology, and End Results, white
      patients from Iowa, from 1973 to 2000, and Olmsted County, from 1980 to 1999.
      RESULTS: Colorectal cancer was observed in 6 ulcerative colitis patients vs 5.38
      expected (SIR, 1.1; 95% confidence interval [CI], 0.4-2.4), but 4 of these
      occurred among those with extensive colitis or pancolitis (SIR, 2.4; 95% CI, 0.6
      6.0). Six Crohn's disease patients (vs 3.2 expected) developed colorectal cancer
      (SIR, 1.9; 95% CI, 0.7-4.1). Three Crohn's disease patients developed small-bowel
      cancer vs 0.07 expected (SIR, 40.6; 95% CI, 8.4-118). CONCLUSIONS: The risk for
      colorectal cancer was not increased among ulcerative colitis patients overall,
      but appeared to be increased among those with extensive colitis. The colorectal
      cancer risk was increased slightly among Crohn's disease patients, who also had a
      40-fold excess risk for small-bowel cancer.

PMID- 16618398
TI  - Association of 6-thioguanine nucleotide levels and inflammatory bowel disease
      activity: a meta-analysis.
AB  - BACKGROUND & AIMS: 6-Thioguanine nucleotide (6-TGN) levels have been proposed to
      correlate with inflammatory bowel disease (IBD) activity among patients treated
      with azathioprine or 6-mercaptopurine (6-MP). Previous studies, most with small
      sample sizes, yielded conflicting conclusions. Our aim was to pool the available
      data to provide a more precise estimate of the association between 6-TGN levels
      and IBD activity. METHODS: We searched Medline and PubMed (from 1966 to November
      2004) and reviewed the reference lists of selected articles. Fixed and random
      effects models were used to test whether mean/median 6-TGN levels differed among
      patients with active disease vs remission and whether 6-TGN levels above a
      threshold of 230-260 pmol/8 x 10(8) red blood cells were associated with clinical
      remission. When studies reported multiple 6-TGN threshold values, we used the
      data for the lower value. RESULTS: We identified 55 articles, 12 of which
      contained data sufficient for inclusion. The mean/median 6-TGN levels were higher
      among patients in remission than in those with active IBD (pooled difference, 66
      pmol/8 x 10(8) red blood cells; 95% confidence interval, 18-113; P = .006), but
      with significant heterogeneity. Excluding the 1 outlier study eliminated this
      heterogeneity. Patients with 6-TGN levels above the threshold value were more
      likely to be in remission (62%) than those below the threshold value (36%)
      (pooled odds ratio, 3.3; 95% confidence interval, 1.7-6.3; P < .001), but with
      significant heterogeneity. Again, excluding the 1 outlier study eliminated this
      heterogeneity. CONCLUSIONS: Although prior studies yielded inconsistent
      conclusions, this analysis strongly supports that higher 6-TGN levels are
      associated with clinical remission.

PMID- 16618399
TI  - Infliximab plus azathioprine for steroid-dependent Crohn's disease patients: a
      randomized placebo-controlled trial.
AB  - BACKGROUND & AIMS: The aim of this study was to evaluate the usefulness of short
      term infliximab combined with azathioprine (AZA) or 6-mercaptopurine (6-MP) in
      steroid-dependent Crohn's disease patients. METHODS: Patients with active disease
      despite prednisone given for more than 6 months were eligible and were stratified
      as follows: the failure stratum consisted of patients receiving AZA/6-MP at a
      stable dose for more than 6 months, and the naive stratum consisted of patients
      not treated previously with AZA/6-MP. Patients were randomized to infliximab 5
      mg/kg or placebo at weeks 0, 2, and 6. All patients were treated with AZA/6-MP
      maintained at a stable dose throughout the 52 weeks of the study. The primary end
      point was remission off steroids at week 24. RESULTS: Among the 113 enrolled
      patients (55 in the failure stratum), 57 were assigned to infliximab. At week 24,
      the success rate (intent-to-treat analysis) was higher in the infliximab group
      than in the placebo group (57% vs 29%; P = .003); at weeks 12 and 52, the
      corresponding rates were 75% vs 38% (P < .001) and 40% vs 22% (P = .04),
      respectively. In each stratum, the success rate was significantly higher in the
      infliximab group at weeks 12 and 24, and a trend was found at week 52. In the
      failure stratum, only 27% of the patients in the infliximab group were still in
      remission off steroids, compared with 52% in the naive stratum. Steroid
      resistance was less common and the cumulative dose of prednisone was lower in the
      infliximab group. CONCLUSIONS: Infliximab plus AZA/6-MP is more effective than
      AZA/6-MP alone in steroid-dependent Crohn's disease patients.

PMID- 16618400
TI  - Impaired viscerosomatic reflexes and abdominal-wall dystony associated with
      bloating.
AB  - BACKGROUND & AIMS: Abdominal bloating is a frequent complaint in irritable bowel
      syndrome (IBS), but its underlying mechanism remains uncertain. Our aim was to
      determine whether the abdominal wall, specifically its adaptation to intra
      abdominal volumes, plays a role. METHODS: In 12 patients complaining of abdominal
      bloating (8 IBS and 4 functional bloating) and in 12 healthy controls, the effect
      of colonic gas load (24 mL/min rectal gas infusion for 1 hour) on perception
      (measured by a 0-6 scale), abdominal girth, and muscular activity was tested.
      With the participants sitting on an ergonomic chair and the trunk erect,
      multichannel electromyography was measured via bipolar surface electrodes located
      over the upper and lower rectus abdominis, and the external and internal oblique
      bilaterally. RESULTS: In healthy controls, colonic gas loads produced subjective
      symptoms (score, 3.0 +/- 0.3), objective abdominal distention (girth increment, 6
      +/- 1 mm), and increased the activity of the abdominal muscles (external oblique
      activity, 11% +/- 3% in; P < .05 vs basal). At the same infused gas volumes, the
      patients developed significantly more symptoms (score, 4.5 +/- 0.4) and abdominal
      distention (11 +/- 1 mm; P < .05 vs healthy for both). These abnormal responses
      were associated with failed tonic contraction of the abdominal wall (external
      oblique activity change, -1% +/- 4%; P value not significant vs basal) and
      paradoxic relaxation of the internal oblique (activity reduction, 26% +/- 7%; P <
      .01 vs basal). CONCLUSIONS: In patients with bloating, abdominal perception and
      distention in response to intra-abdominal volume increments are exaggerated
      markedly and associated with muscular dystony of the abdominal wall.

PMID- 16618401
TI  - Risk factors for initial surgery in pediatric patients with Crohn's disease.
AB  - BACKGROUND & AIMS: The cumulative incidence of surgery ranges from 40%-70% at 10
      years from the time of diagnosis of Crohn's disease in adults. We retrospectively
      determined the cumulative incidence of and risk factors for surgery (intestinal
      resection) in pediatric patients with Crohn's disease. METHODS: Uniform data from
      989 consecutive Crohn's disease patients (age 0-17 years at diagnosis), collected
      from 6 different pediatric centers between January 2000 and November 2003 and
      stored in the Pediatric IBD Consortium Registry, were analyzed. RESULTS: Median
      follow-up time was 2.8 years (range, 1 day to 16.7 years). One hundred twenty
      eight patients underwent surgery. Kaplan-Meier survival estimates of the
      cumulative incidence of surgery were 17% at 5 years and 28% at 10 years from the
      diagnosis of inflammatory bowel disease. Univariate Cox proportional hazards
      models showed leukocytosis (2.85 [hazard ratio]; P = .02), hypoalbuminemia (3.41;
      P = .05), and anti-Saccharomyces cerevisiae antibody (ASCA) positivity (3.43; P =
      .05) were associated with increased risk for surgery. Multivariate Cox models
      showed female gender (1.49; P = .03), initial diagnosis of ulcerative colitis
      (3.63; P < .0001), poor growth at presentation (2.16; P = .007), and abscess
      (1.90; P = .009), fistula (2.30; P = .0005), or stricture (3.41; P < .0001)
      development were associated with increased risk for surgery. Age 3-5 years (0.26;
      P = .01) or 6-12 years (0.62; P = .01) at diagnosis, fever at presentation (0.50;
      P = .03), and treatment with infliximab (0.36; P = .0005) or 5-aminosalicylic
      acid (0.44; P < .0001) were associated with decreased risk for surgery.
      CONCLUSIONS: Risk stratification during the course of Crohn's disease in
      pediatric patients will help to guide therapy that may improve the natural
      history of disease and decrease the need for surgery.

PMID- 16618402
TI  - Familial expression of anti-Escherichia coli outer membrane porin C in relatives
      of patients with Crohn's disease.
AB  - BACKGROUND & AIMS: Crohn's disease (CD) is a genetically complex disorder with
      strong familial aggregation. Pathogenesis appears to involve dysregulation of the
      immune response to endogenous bacteria. Anti-Escherichia coli outer membrane
      porin C (anti-OmpC) expression reflects an exaggerated response to commensal
      bacteria and occurs with higher frequency in CD. The aim of this study was to
      determine whether there is familial aggregation and genetic determination of anti
      OmpC expression in CD families. METHODS: Study groups consisted of 787 CD
      patients, 389 ulcerative colitis (UC) patients, 619 unaffected relatives, and 216
      healthy controls. Serum anti-OmpC was detected by enzyme-linked immunosorbent
      assay. RESULTS: CD patients had a greater percentage of anti-OmpC than UC
      patients and healthy controls. Anti-OmpC expression was more frequent in
      unaffected relatives from CD-only or mixed families, compared with healthy
      controls (P = .002 and .0001, respectively), and it was more frequent in UC
      patients from mixed families than those from UC-only families (P = .02). There
      was a significant familiality in anti-OmpC expression: P = .02 for qualitative
      concordance and P < .0001 for quantitative intraclass correlation. The
      heritability estimate for anti-OmpC level was .39 (P < .0001). CONCLUSIONS: Anti
      OmpC is a heritable immunophenotype. Increased anti-OmpC expression in the
      unaffected family members of CD patients suggests that anti-OmpC may be an
      immunologic risk marker for CD. That UC patients in mixed families had a higher
      response to OmpC than those in UC-only families indicates pathophysiologic
      heterogeneity within UC.

PMID- 16618403
TI  - Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72
      weeks of peginterferon-alfa-2a plus ribavirin.
AB  - BACKGROUND & AIMS: The treatment of patients infected with hepatitis C virus
      (HCV) type 1 remains a challenge necessitating innovative strategies to improve
      treatment outcome. The extension of treatment duration beyond 48 weeks is one
      possible strategy to address this problem. METHODS: The efficacy and safety of 48
      weeks (group A, N = 230) vs 72 weeks (group B, N = 225) of treatment with
      pegylated-interferon-alfa-2a (180 microg/wk) plus ribavirin (800 mg/day) were
      studied in treatment-naive patients with HCV type 1 infection. On-treatment and
      sustained virologic response (SVR) 24 weeks after stopping treatment was assessed
      by qualitative reverse-transcription polymerase chain reaction (sensitivity 50
      IU/mL). RESULTS: Overall, no significant differences could be observed in the
      treatment outcome between both groups. End-of-treatment and SVR rates in groups A
      and B were 71% vs 63% and 53% vs 54%, respectively. Patients with undetectable
      HCV-RNA levels already at weeks 4 and 12 had excellent SVR rates ranging from 76%
      to 84% regardless of treatment group, whereas patients shown to be still HCV-RNA
      positive at week 12 achieved significantly higher SVR rates when treated for 72
      instead of 48 weeks (29% vs 17%, P = .040). A particular benefit from extended
      treatment duration was seen in patients with low-level viremia (<6000 IU/mL) at
      week 12. The frequency and intensity of adverse events was similar between the 2
      groups. CONCLUSIONS: Extended treatment duration generally is not recommended in
      HCV type 1 infection and should be reserved only for patients with slow virologic
      response defined as HCV-RNA positive at week 12 but negative at week 24.

PMID- 16618404
TI  - Pegylated interferon alfa-2b plus ribavirin in the retreatment of interferon
      ribavirin nonresponder patients.
AB  - BACKGROUND & AIMS: Inadequate data are available about retreatment of
      nonresponders to interferon (IFN) and ribavirin. Thus, this study evaluated the
      efficacy and tolerability of a 48-week therapy with pegylated IFN-alpha-2b plus
      high-dose ribavirin in patients who have failed to respond to the combination.
      Treatment up to 48 weeks also in patients who have failed to clear hepatitis C
      virus (HCV) RNA by week 24 was also evaluated. METHODS: One hundred forty-one
      patients who previously did not respond to IFN and ribavirin, 86% with genotype 1
      or 4 infection, 52% with high viral load (>800.000 IU/mL), 22% with cirrhosis,
      were retreated with pegylated IFN-alpha-2b 1.5 microg/kg per week and ribavirin
      1000-1200 mg/day for 48 weeks and followed up for 24 weeks. RESULTS: By intent-to
      treat analysis, 20% of patients achieved a sustained virologic response (SVR).
      SVR of genotype 1 patients was 19%. Independent predictors of SVR were low gamma
      glutamyltransferase levels (OR, 22.9; 95% CI: 6.6-79.6) and low viral load (OR,
      3.8; 95% CI: 1.1-12.6). Twelve (23%) out of 51 patients who were HCV RNA positive
      after 24 weeks of therapy achieved a late virologic response (after week 24) and
      5 (10%) of them, all with genotype 1, achieved an SVR. Genotype was not
      associated with response (P = .2) or with early response (P = .3). CONCLUSIONS:
      Retreatment with pegylated IFN-alpha-2b and ribavirin of multi-experienced and
      "difficult to treat" nonresponder patients produced a very promising SVR.
      Accurate selection of patients, such as those with low viral load and low gamma
      glutamyltransferase levels, and prolongation of therapy beyond 24 weeks also in
      HCV RNA-positive patients may further increase the rate of SVR.

PMID- 16618405
TI  - Productive replication of hepatitis C virus in perihepatic lymph nodes in vivo:
      implications of HCV lymphotropism.
AB  - BACKGROUND & AIMS: The pathogenesis of chronic hepatitis C is poorly understood.
      This study examines the ability of hepatitis C virus (HCV) to infect, replicate
      in, and produce progeny virus from perihepatic lymph nodes in vivo. METHODS:
      Lymph node (LN) biopsy specimens were taken from 20 patients with HCV genotype 1
      infection and end-stage liver disease and 20 noninfected negative controls.
      Sections were probed with HCV RNA strand-specific riboprobes and antibodies
      specific for HCV core and nonstructural region 3 antigens plus B-cell (CD20) and
      T-cell (CD2) antigens. In a selected case, HCV quasispecies in serum, peripheral
      blood mononuclear cells, liver, and perihepatic lymph nodes were analyzed by
      clonal frequency analysis and sequencing. RESULTS: HCV infection was confirmed in
      17 of 20 (85%) of lymph node specimens by in situ hybridization, and HCV
      replication was confirmed in 50% of cases by detection of HCV replicative
      intermediate RNA. HCV core and nonstructural 3 antigens were detected in lymph
      nodes by immunocytochemistry. Infected cell phenotypes were primarily CD20 B
      cells, although other cell types were positive for HCV replication markers.
      Quasispecies analysis in one case indicated that 68% of variants circulating in
      serum were also present in lymphoid tissues, and only 40% of serum variants were
      identified in liver, documenting a major contribution of lymphoid replication to
      HCV viremia. CONCLUSIONS: HCV lymphotropism provides new insights into the
      complex pathobiology of chronic hepatitis C in humans. We demonstrate for the
      first time a major contribution of extrahepatic HCV replication to circulating
      virus in serum (viremia).

PMID- 16618406
TI  - Ubiquitous activation of Ras and Jak/Stat pathways in human HCC.
AB  - BACKGROUND & AIMS: Although the natural history and pathologic characteristics of
      human hepatocellular carcinoma (HCC) are well documented, the molecular
      pathogenesis of HCC remains poorly understood. Here, we define the role for Ras
      and Janus kinase (Jak)/signal transducer and activator of transcription (Stat)
      pathways in human HCC. METHODS: Promoter and genomic status of Ras and Jak/Stat
      inhibitors were assessed in 80 HCCs by methylation-specific polymerase chain
      reaction and microsatellite analysis. Activation of Ras and Jak/Stat signaling
      pathways was determined by DNA sequencing, Western blot, and immunoprecipitation
      analysis. Suppression of Ras and Jak/Stat pathways in HCC cell lines was
      evaluated by viability and apoptosis assays. RESULTS: Activation of Ras and
      Jak/Stat pathways was enhanced in all HCCs when compared with nonneoplastic
      surrounding and normal livers coincidently with the suppression of at least 1 Ras
      (RASSF1A and/or NORE1A) and 2 Jak/Stat inhibitors (cytokine-inducible SH2-protein
      [CIS]; suppressor of cytokine signaling [SOCS]1, 2, 3; and SH2-containing
      phosphatases [SHP1]). HCC associated with cirrhosis showed significantly higher
      frequency of RASSF1A, CIS, and SOCS1 promoter methylation than HCC without
      cirrhosis (P < .002, P < .02, and P < .02, respectively). Furthermore, aberrant
      methylation of NORE1A and SOCS3 promoters was observed only in a subclass of HCC
      with poor survival, suggesting that inactivation of these 2 genes might be
      involved in HCC progression. Combined treatment of HCC cell lines with Ras and
      Jak/Stat inhibitors as well as with the demethylating agent zebularine induced a
      strong apoptotic response. CONCLUSIONS: These data demonstrate the ubiquitous
      activation of Ras and Jak/Stat pathways in HCC and suggest the potential use of
      Ras and Jak/Stat inhibitors and demethylating agents as therapeutic modality for
      human liver cancer.

PMID- 16618407
TI  - Acute hepatitis A infection in pregnancy is associated with high rates of
      gestational complications and preterm labor.
AB  - BACKGROUND & AIMS: Hepatitis A virus (HAV) infection is the most common cause of
      acute hepatitis but is rarely reported during pregnancy. Our aim was to evaluate
      the impact of acute HAV infection on pregnancy outcome. METHODS: Consecutive
      admissions of 79,458 pregnant females during a 25-year period were
      retrospectively reviewed. RESULTS: Thirteen cases of second and third trimester
      HAV infection were found and evaluated. Nine of the 13 patients (69%) developed
      gestational complications, including premature contractions (n = 4), placental
      separation (n = 2), premature rupture of membranes (n = 2), and vaginal bleeding
      (n = 1). In 8 of these patients, complications led to preterm labor, at a median
      of 34 gestational weeks (range, 31-37 weeks). Delivery was vaginal in 12 of the
      13 cases; fetal distress was noted in a single case, and meconium in amniotic
      fluid in 2 cases. Median birth weight was 1778 grams and 3040 grams in preterm
      and term deliveries, respectively (P < .05). Child outcome was favorable in all
      cases. In 4 cases, neonatal serum HAV RNA levels were measured and found
      negative. The presence of fever and hypoalbuminemia were associated with delivery
      at an earlier gestational week. There was a positive relation between gestational
      week at diagnosis of HAV infection and birth week (r = 0.68, P = .02), suggesting
      a causality relationship. All mothers featured full recovery from HAV infection.
      CONCLUSIONS: Acute HAV infection during pregnancy is associated with high risk of
      maternal complications and preterm labor. HAV serology and maternal vaccination
      during prepregnancy evaluation should be considered in areas of the world in
      which susceptible adult populations exist.

PMID- 16618408
TI  - Hyponatremia impairs early posttransplantation outcome in patients with cirrhosis
      undergoing liver transplantation.
AB  - BACKGROUND & AIMS: Hyponatremia is associated with reduced survival in patients
      with cirrhosis awaiting liver transplantation. However, it is not known whether
      hyponatremia also represents a risk factor of poor outcome after transplantation.
      We aimed to assess the effects of hyponatremia at the time of transplantation on
      posttransplantation outcome in patients with cirrhosis. METHODS: Two-hundred
      forty-one consecutive patients with cirrhosis submitted to liver transplantation
      during a 4-year period (January 2000-December 2003) were included in the study.
      The main end point was survival at 3 months after transplantation. Secondary end
      points were complications within the first month after transplantation. RESULTS:
      Patients with hyponatremia (serum sodium lower than 130 mEq/L) had a greater
      incidence of neurologic disorders, renal failure, and infectious complications
      than patients without hyponatremia (odds ratio; 4.6, 3.4 and 2.7, respectively)
      within the first month after transplantation. By contrast, hyponatremia was not
      associated with an increased incidence of severe intra-abdominal bleeding, acute
      rejection, or vascular and biliary complications. Hyponatremia was an independent
      predictive factor of early posttransplantation survival. Three-month survival of
      patients with hyponatremia was 84% compared with 95% of patients without
      hyponatremia (P < .05). Survival was similar after 3 months. CONCLUSIONS: In
      patients with cirrhosis, the presence of hyponatremia is associated with a high
      rate of neurologic disorders, infectious complications, and renal failure during
      the first month after transplantation and reduced 3-month survival. In cirrhosis,
      hyponatremia should be considered not only a risk factor of death before
      transplantation but also a risk factor of impaired early posttransplantation
      outcome.

PMID- 16618409
TI  - Predominance of hepatitis B virus YMDD mutants is prognostic of viral DNA
      breakthrough.
AB  - BACKGROUND & AIMS: Hepatitis B virus (HBV) tyrosine, methionine, aspartate,
      aspartate (YMDD) mutants with or without additional compensatory mutations occur
      in chronically infected patients during lamivudine therapy and may be associated
      with accompanying viral breakthrough. The aim of this study was to determine
      whether a predominance of YMDD mutants could be a prognostic marker for
      occurrence of viral DNA breakthrough. METHODS: YMDD genotypes in 740 consecutive
      samples collected from 116 patients throughout lamivudine treatment were
      retrospectively analyzed using a matrix-assisted laser desorption/ionization time
      of flight mass spectrometry (MALDI-TOF MS)-based genotyping assay, termed
      restriction fragment mass polymorphism (RFMP). RFMP exploits differences in
      molecular masses between wild-type and variant bases of rtM204V/I following PCR
      amplification of HBV DNA with a lower limit of detection being 100 copies/mL.
      RESULTS: The study demonstrated that YMDD mutants occur throughout the course of
      lamivudine therapy irrespective of occurrence of viral DNA breakthrough,
      indicating that a mere detection of YMDD mutants could not sufficiently predict
      the viral DNA breakthrough, although presence of YMDD mutants is associated with
      high incidence of viral DNA breakthrough (odds ratio, 7.8; P = .0012; relative
      risk = 8.7%), and a 5-fold predominance of YMDD mutant to wild-type virus was
      significantly associated with viral DNA breakthrough (odds ratio, 604.5; P <
      .0001; relative risk = 93.8%). CONCLUSIONS: Close and periodical testing by RFMP
      assay should be useful to detect the predominance of YMDD mutants for monitoring
      drug resistance, enabling early intervention and prevention.

PMID- 16618410
TI  - High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with
      progressive liver diseases.
AB  - BACKGROUND & AIMS: The interactions among pre-S deletion, precore (PC) mutation,
      and basal core promoter (BCP) mutation in various stages of chronic hepatitis B
      virus (HBV) infection remain unclear and were thus investigated in this study.
      METHODS: The sequences of the pre-S region and the BCP (A1762T, G1764A) and PC
      (G1896A) mutations were determined in 46 HBV chronic carriers (CC) and 106 age
      matched carriers with different stages of liver diseases, including 38 chronic
      hepatitis (CH), 18 cirrhosis (LC), and 50 hepatocellular carcinoma (HCC).
      RESULTS: A higher prevalence of pre-S deletion and BCP and PC mutations was found
      in carriers with progressive liver diseases compared with the CC group. By
      logistic regression analysis, patients with pre-S deletion and BCP mutation were
      significantly associated with the development of progressive liver diseases than
      those without. Combination of mutations rather than single mutation was
      associated with the development of progressive liver diseases, especially in
      combination with pre-S deletion. Sequencing analysis showed that the deleted
      regions were more often in the 3' terminus of pre-S1 and the 5' terminus of pre
      S2. Further mapping of these pre-S deletion sequences found that all the deletion
      regions encompassed T- and B-cell epitopes, and most of them lost 1 or more
      functional sites. CONCLUSIONS: Our data indicate that patients with progressive
      liver diseases have a higher frequency of pre-S deletion.

PMID- 16618411
TI  - Gastrin increases murine intestinal crypt regeneration following injury.
AB  - BACKGROUND & AIMS: A number of growth factors affect the regeneration of
      intestinal epithelia following injury, but the effects of amidated gastrin have
      not previously been assessed. We therefore investigated the effects of gastrin on
      intestinal regeneration following a range of stimuli. METHODS: Intestinal crypt
      regeneration was assessed in transgenic mice overexpressing amidated gastrin (INS
      GAS) and mice in which hypergastrinemia was induced using omeprazole, following
      gamma-radiation, 5-fluorouracil, and dextran sulphate sodium (DSS). Abundance of
      the CCK-2 receptor was assessed in intestinal epithelia and IEC-6 intestinal
      epithelial cells following gamma-radiation. RESULTS: Four days following 14 Gy
      gamma-radiation, or 2 injections of 400 mg/kg 5-fluorouracil, INS-GAS mice
      exhibited significantly increased small intestinal and colonic crypt survival
      compared with their wild-type counterparts (FVB/N). INS-GAS mice treated with 3%
      DSS for 5 days showed less weight loss and increased colonic crypt regeneration
      at 8 days compared with FVB/N. Increased small intestinal and colonic crypt
      survival was also demonstrated following gamma-radiation in FVB/N mice rendered
      hypergastrinemic using omeprazole. The increased crypt survival in INS-GAS mice
      following 14 Gy gamma-radiation was inhibited by administration of a CCK-2
      receptor antagonist (YF476). Increased abundance of the CCK-2 receptor was
      demonstrated in intestinal epithelia following 14 Gy gamma-radiation by Western
      blotting and immunohistochemistry. Similarly, increased CCK-2 receptor mRNA
      abundance and increased 125I-gastrin binding was demonstrated in IEC-6 cells
      following 4 Gy gamma-radiation. CONCLUSIONS: Hypergastrinemia increases
      regeneration of intestinal epithelia following diverse forms of injury. Induction
      of the CCK-2 receptor in damaged epithelium confers potential for protection
      against injury by administration of gastrin.

PMID- 16618412
TI  - Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent
      biological activity of Helicobacter pylori CagA.
AB  - BACKGROUND & AIMS: Helicobacter pylori CagA-positive strain is associated with
      gastric adenocarcinoma. CagA is delivered into gastric epithelial cells, where it
      undergoes tyrosine phosphorylation at the EPIYA sites by Src family kinases
      (SFKs). Owing to homologous recombination within the 3'-region of the cagA gene,
      4 distinct EPIYA sites, each of which is defined by surrounding sequences, are
      variably assembled in both number and order among CagA proteins from different
      clinical H pylori isolates. Tyrosine-phosphorylated CagA specifically binds and
      deregulates SHP-2 via the Western CagA-specific EPIYA-C or East Asian CagA
      specific EPIYA-D site, and C-terminal Src kinase (Csk) via the EPIYA-A or EPIYA-B
      site. Here we investigated the influence of EPIYA-repeat polymorphism on the CagA
      activity. METHODS: A series of EPIYA-repeat variants of CagA were expressed in
      AGS gastric epithelial cells and the ability of individual CagA to bind SHP-2 or
      Csk was determined by the sequential immunoprecipitation and immunoblotting
      method. RESULTS: CagA proteins carrying multiple EPIYA-C or EPIYA-D sites bound
      and deregulated SHP-2 more strongly than those having a single EPIYA-C or EPIYA
      D. Furthermore, the ability of CagA to bind Csk was correlated with the number of
      EPIYA-A and EPIYA-B sites. Because Csk inhibits SFK, CagA with greater Csk
      binding activity more strongly inhibited Src-dependent CagA phosphorylation and
      more effectively attenuated induction of cell elongation caused by CagA-SHP-2
      interaction. CONCLUSIONS: EPIYA-repeat polymorphism of CagA greatly influences
      the magnitude and duration of phosphorylation-dependent CagA activity, which may
      determine the potential of individual CagA as a bacterial virulence factor that
      directs gastric carcinogenesis.

PMID- 16618413
TI  - Bile acids induce ectopic expression of intestinal guanylyl cyclase C Through
      nuclear factor-kappaB and Cdx2 in human esophageal cells.
AB  - BACKGROUND & AIMS: Although progression to adenocarcinoma at the gastroesophageal
      junction reflects exposure to acid and bile acids associated with reflux,
      mechanisms mediating this transformation remain undefined. Guanylyl cyclase C (GC
      C), an intestine-specific tumor suppressor, may represent a mechanism-based
      marker and target of transformation at the gastroesophageal junction. The present
      studies examine the expression of GC-C in normal tissues and tumors from
      esophagus and stomach and mechanisms regulating its expression by acid and bile
      acids. METHODS: Gene expression was examined by reverse-transcription polymerase
      chain reaction, promoter analysis, immunohistochemistry, immunoblotting, and
      functional analysis. Promoter transactivation was quantified by using luciferase
      constructs and mutational analysis. DNA binding of transcription factors was
      examined by electromobility shift analysis. RESULTS: GC-C mRNA and protein were
      ectopically expressed in approximately 80% of adenocarcinomas arising in, but not
      in normal, esophagus and stomach. Similarly, in OE19 human esophageal cancer
      cells, deoxycholate and acid induced expression of GC-C. This was associated with
      the induction of expression of Cdx2, a transcription factor required for GC-C
      expression. In turn, induction of Cdx2 expression by deoxycholate was mediated by
      binding sites in the proximal promoter for nuclear factor kappaB (NF-kappaB).
      Furthermore, deoxycholate increased NF-kappaB activity, associated with nuclear
      translocation and Cdx2 promoter binding of the NF-kappaB subunit p50. Moreover, a
      dominant negative construct for NF-kappaB prevented deoxycholate-induced p50
      nuclear translocation and activation of the Cdx2 promoter. CONCLUSIONS:
      Transformation associated with reflux at the gastroesophageal junction reflects
      activation by bile acid and acid of a transcriptional program involving NF-kappaB
      and Cdx2, which mediate intestinal metaplasia and ectopic expression of GC-C.

PMID- 16618414
TI  - The cell adhesion molecule l1 is required for chain migration of neural crest
      cells in the developing mouse gut.
AB  - BACKGROUND & AIMS: During development, the enteric nervous system is derived from
      neural crest cells that emigrate from the hindbrain, enter the foregut, and
      colonize the gut. Defects in neural crest migration can result in intestinal
      aganglionosis. Hirschsprung's disease (congenital aganglionosis) is a human
      condition in which enteric neurons are absent from the distal bowel. A number of
      clinical studies have implicated the cell adhesion molecule L1 in Hirschsprung's
      disease. We examined the role of L1 in the migration of neural crest cells
      through the developing mouse gut. METHODS: A variety of in vitro and in vivo
      assays were used to examine: (1) the effect of L1 blocking antibodies or
      exogenous soluble L1 protein known to compromise L1 function on the rate of crest
      cell migration, (2) the effect of blocking L1 activity on the dynamic behavior of
      crest cells using time-lapse microscopy, and (3) whether the colonization of the
      gut by crest cells in L1-deficient mice differs from control mice. RESULTS: We
      show that L1 is expressed by neural crest cells as they colonize the gut.
      Perturbation studies show that disrupting L1 activity retards neural crest
      migration and increases the number of solitary neural crest cells. L1-deficient
      mice show a small but significant reduction in neural crest cell migration at
      early developmental stages, but the entire gastrointestinal tract is colonized.
      CONCLUSIONS: L1 is important for the migration of neural crest cells through the
      developing gut and is likely to be involved in the etiology of Hirschsprung's
      disease.

PMID- 16618415
TI  - Stomach development is dependent on fibroblast growth factor 10/fibroblast growth
      factor receptor 2b-mediated signaling.
AB  - BACKGROUND & AIMS: Fibroblast growth factors (Fgfs) and their receptors (Fgfrs)
      are important intercellular signaling molecules that are essential to mammalian
      embryonic development. The signaling pathways between endoderm-derived gastric
      epithelium and the surrounding mesenchyme are largely unknown; however, the
      developmental expression profile of the IIIb isoform of Fgfr2 (Fgfr2b) and its
      main ligand, Fgf10, suggest that they may be strong candidates. Mice lacking
      either component (Fgfr2b-/- or Fgf10-/-) were examined to determine the role of
      Fgfr2b-mediated signaling during gastric organogenesis. METHODS: Stomachs from
      embryonic day 13.5-18.5 Fgfr2b-/-, Fgf10-/-, and wild-type littermates were
      collected and analyzed by conventional histology, immunohistochemistry, in situ
      hybridization, and electron microscopy. RESULTS: Fgfr2b-/- and Fgf10-/- fetuses
      had stomachs smaller than wild-type, consisting of relatively proportionate
      forestomach but disproportionately reduced glandular stomach, the mucosa of which
      has low cytoarchitectural complexity with a spiral arrangement of large mucosal
      folds. During mid to late fetal stages (embryonic day 15.5-18.5), epithelial
      differentiation to mucous and chief cell lineages was rudimentary, with no
      expression of several early cytodifferentiation markers including GATA4, GATA6,
      and H+/K+-adenosine triphosphatase and abnormal expression of members of the
      hedgehog family of signaling molecules. CONCLUSIONS: Fgfr2b and Fgf10 are part of
      a signaling network with Sonic hedgehog and Indian hedgehog that are essential to
      anterior-posterior and radial patterning in gastric development.

PMID- 16618416
TI  - Targeted deletion of FATP5 reveals multiple functions in liver metabolism:
      alterations in hepatic lipid homeostasis.
AB  - BACKGROUND & AIMS: Fatty acid transport protein 5 (FATP5/Slc27a5) has been shown
      to be a multifunctional protein that in vitro increases both uptake of
      fluorescently labeled long-chain fatty acid (LCFA) analogues and bile
      acid/coenzyme A ligase activity on overexpression. The aim of this study was to
      further investigate the diverse roles of FATP5 in vivo. METHODS: We studied FATP5
      expression and localization in liver of C57BL/6 mice in detail. Furthermore, we
      created a FATP5 knockout mouse model and characterized changes in hepatic lipid
      metabolism (this report) and bile metabolism (the accompanying report by Hubbard
      et al). RESULTS: FATP5 is exclusively expressed by the liver and localized to the
      basal plasma membrane of hepatocytes, congruent with a role in LCFA uptake from
      the circulation. Overexpression of FATP5 in mammalian cells increased the uptake
      of 14C-oleate. Conversely, FATP5 deletion significantly reduced LCFA uptake by
      hepatocytes isolated from FATP5 knockout animals. Moreover, FATP5 deletion
      resulted in lower hepatic triglyceride and free fatty acid content despite
      increased expression of fatty acid synthetase and also caused a redistribution of
      lipids from liver to other LCFA-metabolizing tissues. Detailed analysis of the
      hepatic lipom of FATP5 knockout livers showed quantitative and qualitative
      alterations in line with a decreased uptake of dietary LCFAs and increased de
      novo synthesis. CONCLUSIONS: Our findings support the hypothesis that efficient
      hepatocellular uptake of LCFAs, and thus liver lipid homeostasis in general, is
      largely a protein-mediated process requiring FATP5. These new insights into the
      physiological role of FATP5 should lead to an improved understanding of liver
      function and disease.

PMID- 16618417
TI  - Mice deleted for fatty acid transport protein 5 have defective bile acid
      conjugation and are protected from obesity.
AB  - BACKGROUND & AIMS: Fatty Acid Transport Protein 5 (FATP5) is a liver-specific
      member of the FATP/Slc27 family, which has been shown to exhibit both fatty acid
      transport and bile acid-CoA ligase activity in vitro. Here, we investigate its
      role in bile acid metabolism and body weight homeostasis in vivo by using a novel
      FATP5 knockout mouse model. METHODS: Bile acid composition was analyzed by mass
      spectroscopy. Body weight, food intake, energy expenditure, and fat absorption
      were determined in animals fed either a low- or a high-fat diet. RESULTS:
      Although total bile acid concentrations were unchanged in bile, liver, urine, and
      feces of FATP5 knockout mice, the majority of gallbladder bile acids was
      unconjugated, and only a small percentage was conjugated. Primary, but not
      secondary, bile acids were detected among the remaining conjugated forms in FATP5
      deletion mice, suggesting a specific requirement for FATP5 in reconjugation of
      bile acids during the enterohepatic recirculation. Fat absorption in FATP5
      deletion mice was largely normal, and only a small increase in fecal fat was
      observed on a high-fat diet. Despite normal fat absorption, FATP5 deletion mice
      failed to gain weight on a high-fat diet because of both decreased food intake
      and increased energy expenditure. CONCLUSIONS: Our findings reveal an important
      role for FATP5 in bile acid conjugation in vivo and an unexpected function in
      body weight homeostasis, which will require further analysis. FATP5 deletion mice
      provide a new model to study the intersection of bile acid metabolism, lipid
      metabolism, and body weight regulation.

PMID- 16618418
TI  - Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via
      an autocrine mechanism.
AB  - BACKGROUND & AIMS: Vascular endothelial growth factor (VEGF) is secreted by
      several epithelia and modulates cellular functions by autocrine and paracrine
      mechanisms. The role of VEGF in cholangiocyte pathophysiology is unknown. We
      evaluated the role of VEGF in the regulation of cholangiocyte proliferation in
      rats that underwent bile duct ligation. METHODS: The expression of VEGF-A and
      VEGF-C and their receptors in cholangiocytes from normal and BDL rats was
      evaluated. Normal or BDL rats were treated with recombinant-VEGF-A or recombinant
      VEGF-C or anti-VEGF antibodies, and proliferation of cholangiocytes was evaluated
      in situ by morphometry and in vitro by proliferating cell nuclear antigen
      immunoblots and MTS assay. In vitro, normal rat cholangiocyte cultures were
      stimulated with r-VEGF-A or r-VEGF-C and proliferation and signal transduction
      were evaluated. RESULTS: We found that (1) cholangiocytes express messenger RNA
      and protein for VEGF-A, VEGF-C, VEGF receptor 2 (VEGFR-2), and VEGF receptor 3
      (VEGFR-3) and secrete VEGF; (2) secretion of VEGF and expression of VEGFR-2 and
      VEGFR-3 increases in BDL cholangiocytes; (3) blocking VEGF in vivo by anti-VEGF-A
      or anti-VEGF-C antibodies decreases cholangiocyte proliferation; (4) the in vivo
      administration of r-VEGF-A or r-VEGF-C induces cholangiocyte proliferation in
      normal rats; and (5) in vitro, VEGF-A increases normal rat cholangiocyte culture
      proliferation by activation of inositol 1,4,5-triphosphate/Ca2+/protein kinase C
      alpha and phosphorylation of Src/ERK1/2. CONCLUSIONS: Cholangiocytes secrete VEGF
      and express VEGFR-2 and VEGFR-3, all of which are amplified in BDL
      cholangiocytes. VEGF induces cholangiocyte proliferation by activation of
      inositol 1,4,5-triphosphate/[Ca2+]i/protein kinase C alpha and phosphorylation of
      Src/ERK1/2. VEGF mediates the adaptive proliferative response of cholangiocytes
      to cholestasis.

PMID- 16618420
TI  - Gene transfer of kringle 1-5 suppresses tumor development and improves prognosis
      of mice with hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Recent studies indicate that kringle 1-5 has a potent and
      specific antiangiogenic activity. Here, we investigated the antitumor effect of
      kringle 1-5 gene transfer on hepatocellular carcinoma in mice. METHODS: The
      inhibitory effect of kringle 1-5 protein on proliferation of bovine capillary
      endothelial cells was evaluated by a tetrazolium-based assay. To study tumor
      growth, intrahepatic metastasis, and survival, liposome/kringle 1-5 complementary
      DNA complexes were injected intravenously in nude mice preimplanted with 1 of 3
      hepatoma cell lines into the liver. Production of kringle 1-5 was tested by
      immunohistochemistry and Western blotting. Intratumoral vessel density was
      quantified. Expression of vascular endothelial growth factor, angiopoietin-1, and
      angiopoietin-2 in tumors was examined by Western blotting. Serum alanine
      aminotransferase and alpha-fetoprotein levels and body weights were measured.
      RESULTS: Proliferation of bovine capillary endothelial cells was inhibited by
      purified kringle 1-5 in a dose-dependent manner. Gene transfer of kringle 1-5
      caused a significant reduction in vessel density with suppression of tumor growth
      of the 3 hepatoma cell lines and serum alpha-fetoprotein levels, prolonged the
      survival period, and reduced the number of intrahepatic metastases. Among the
      analyzed angiogenic factors, kringle 1-5 reduced angiopoietin-2 expression
      levels. Expression of kringle 1-5 protein was detected on hepatoma cells and
      hepatocytes in the liver. However, it did not alter serum alanine
      aminotransferase levels and body weights, suggesting kringle 1-5 lacks severe
      side effects. CONCLUSIONS: Antiangiogenic gene therapy with kringle 1-5
      complementary DNA is a promising safe and effective strategy for suppression of
      growth of hepatocellular carcinoma.

PMID- 16618419
TI  - Increased expression of hepatocyte nuclear factor 6 stimulates hepatocyte
      proliferation during mouse liver regeneration.
AB  - BACKGROUND & AIMS: The hepatocyte nuclear factor 6 (HNF6 or ONECUT-1) protein is
      a cell-type specific transcription factor that regulates expression of hepatocyte
      specific genes. Using hepatocytes for chromatin immunoprecipitation (ChIP)
      assays, the HNF6 protein was shown to associate with cell cycle regulatory
      promoters. Here, we examined whether increased levels of HNF6 stimulate
      hepatocyte proliferation during mouse liver regeneration. METHODS: Tail vein
      injection of adenovirus expressing the HNF6 complementary DNA was used to
      increase hepatic HNF6 levels during mouse liver regeneration induced by partial
      hepatectomy, and DNA replication was determined by bromodeoxyuridine
      incorporation. Cotransfection and ChIP assays were used to determine
      transcriptional target promoters. RESULTS: Elevated expression of HNF6 during
      mouse liver regeneration causes a significant increase in the number of
      hepatocytes entering DNA replication (S phase), and mouse hepatoma Hepa1-6 cells
      diminished for HNF6 levels by small interfering RNA transfection exhibit a 50%
      reduction in S phase following serum stimulation. This stimulation in hepatocyte
      S-phase progression was associated with increased expression of the hepatocyte
      mitogen tumor growth factor alpha and the cell cycle regulators cyclin D1 and
      Forkhead box m1 (Foxm1) transcription factor. Cotransfection and ChIP assays show
      that tumor growth factor alpha, cyclin D1, and HNF6 promoter regions are direct
      transcriptional targets of the HNF6 protein. Coimmunoprecipitation assays with
      regenerating mouse liver extracts reveal an association between HNF6 and FoxM1
      proteins, and cotransfection assays show that HNF6 stimulates Foxm1
      transcriptional activity. CONCLUSIONS: These mouse liver regeneration studies
      show that increased HNF6 levels stimulate hepatocyte proliferation through
      transcriptional induction of cell cycle regulatory genes.

PMID- 16618421
TI  - Recurrent clostridium difficile.

PMID- 16618422
TI  - Sustained engraftment and tissue enzyme activity after liver cell transplantation
      for argininosuccinate lyase deficiency.
AB  - BACKGROUND & AIMS: Donor cell engraftment with expression of enzyme activity is
      the goal of liver cell transplantation for inborn errors of liver metabolism with
      a view to achieving sustained metabolic control. METHODS: Sequential hepatic cell
      transplantations using male and female cells were performed in a 3.5-year-old
      girl with argininosuccinate lyase deficiency over a period of 5 months. Beside
      clinical, psychomotor, and metabolic follow-up, engraftment was analyzed in
      repeated liver biopsies (2.5, 5, 8, and 12 months after first infusion) by
      fluorescence in situ hybridization for the Y-chromosome and by measurement of
      tissue enzyme activity. RESULTS: Metabolic control was achieved together with
      psychomotor catch-up, changing the clinical phenotype from a severe neonatal one
      to a moderate late-onset type. The child was no longer hospitalized and was able
      to attend normal school. Sustained engraftment of male donor liver cells was
      shown in repeated biopsies, reaching 19% at 8 months and 12.5% at the 12-month
      follow-up. XXYY tetraploid donor cells were mainly detected during the infusion
      period (2.5- and 5-month biopsies), whereas in the follow-up 8-month and 1-year
      biopsies, diploid donor cell subpopulations had become dominant. Moreover,
      argininosuccinate lyase activity, originally absent, became measurable in 2
      different biopsy samples at 8 months, reaching 3% of control activity, indicating
      in situ metabolic effect and supporting the clinical evolution to a moderate form
      of the disease. CONCLUSIONS: Liver cell transplantation can achieve donor cell
      engraftment in humans in a significant proportion, leading to sustained metabolic
      and clinical control with psychomotor catch-up.

PMID- 16618423
TI  - Developmental characteristics of adapting mouse small intestine crypt cells.
AB  - BACKGROUND & AIMS: Following massive small bowel resection (SBR), the remnant
      intestine undergoes an adaptive process characterized by increases in a number of
      physiologic and morphologic parameters. These changes are the result of a
      stimulus that increases crypt cell mitosis and augments cellular progression
      along the villus axis. To better define this process, we identified patterns of
      gene expression specifically within adapting intestinal crypt cells following
      SBR. METHODS: Laser capture microdissection was used to isolate mouse intestinal
      crypt cells following SBR or sham operation. Multiple biological and technical
      complementary DNA microarray replicates allowed rigorous statistical analyses for
      identification of important expression profiles. Major groups of genes were
      classified as to site of action, functional pathway, and possible regulatory
      groups. RESULTS: A total of 300 genes differentially expressed at significant
      levels within adapting crypt enterocytes were analyzed. Comparison of this list
      of differentially expressed adapting crypt cell genes with a generalized mouse
      gene expression database (from 82 developing and adult mouse tissues) showed the
      greatest overlap with developing and immature intestinal tissues. We identified
      prominent groups of genes involved with cell growth, signal transduction, and
      nucleic acid binding. Genes not previously shown to be involved with adaptation
      or development and maturation were identified. CONCLUSIONS: Identification of
      similar genes coordinately regulated during both adaptation and development,
      processes that share key morphologic features, provides a basis for new
      mechanistic insights into these shared characteristics.

PMID- 16618424
TI  - Advanced imaging and technology in gastrointestinal neoplasia: summary of the AGA
      NCI Symposium October 4-5, 2004.
AB  - Imaging and other advanced technologies for detection of gastrointestinal cancers
      are undergoing a major revolution on several fronts. This is facilitated by
      convergence of key technologies including advanced endoscopic-detection systems,
      more specific contrast agents, rapid and high-resolution cross-sectional imaging,
      and miniaturization of construction systems for making all imaging equipment
      smaller and less invasive. This convergence is occurring along traditional
      translational research pathways (clinical medicine-molecular biology) as well as
      nontraditional lines (clinical medicine-optical physics/engineering and molecular
      biology-optical physics/engineering). These new efforts are producing a wide
      array of technologies aimed at improving detection, classification, and
      monitoring of gastrointestinal neoplasia, especially for colorectal and
      esophageal cancer because of easier accessibility. A critical goal is to detect
      lesions at their premalignant stages, thereby permitting meaningful intervention.
      Inspired by these advances, the American Gastroenterological Association and the
      National Cancer Institute sponsored a symposium held in Bethesda, MD, from
      October 4-5, 2004, bringing together leading investigators with diverse
      backgrounds in imaging technology. The aims of this symposium were to summarize
      the state of the art and priorities for research in the coming decade in the
      field of imaging and advanced technology for gastrointestinal neoplasia. In this
      overview, we summarize the salient results of that symposium. The initial
      sections discuss the major technologies in each area of endoluminal imaging and
      molecular imaging followed by applications to specific diseases such as Barrett's
      esophagus and colon neoplasia. Each section focuses on the current state of the
      art then lists major priorities for research in the field.

PMID- 16618425
TI  - Ins and outs modulating hepatic triglyceride and development of nonalcoholic
      fatty liver disease.

PMID- 16618426
TI  - The changing face of colorectal cancer in inflammatory bowel disease: progress at
      last!

PMID- 16618427
TI  - When is too much enough?

PMID- 16618428
TI  - Infliximab and azathioprine: bridge or parachute?

PMID- 16618430
TI  - Lymphoma risk with azathioprine/6-MP therapy-read beyond the headlines.

PMID- 16618429
TI  - Optimizing outcomes in hepatitis C: is treatment beyond 48 weeks ever justified?

PMID- 16618432
TI  - Hypoadiponectinemia and NASH: cause or effect?

PMID- 16618431
TI  - Embarrassment is a major barrier to colon cancer prevention, especially among
      women: a call to action.

PMID- 16618433
TI  - Treatment of iron deficiency.

PMID- 16618435
TI  - Effects of aging of the population.

PMID- 16618437
TI  - Uncovered transjugular intrahepatic portosystemic shunt for refractory ascites.

PMID- 16618438
TI  - Addenda and corrections concerning Friedrich Krukenberg.

PMID- 16618440
TI  - Prevalence of Barrett's Esophagus.

PMID- 16618442
TI  - Proceedings from the 11th Meeting of the European Placenta Group and the 11th
      Meeting of the International Federation of Placental Associations, Glasgow,
      Scotland, September 2005.

PMID- 16618445
TI  - Transfusion-associated graft-versus-host disease.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) is a relatively rare
      and interesting entity. Despite a range of pathophysiological and therapeutic
      approaches, it has a high mortality. It is possible to prevent the disease by
      prophylaxis only. It is possible to miss the entity in routine clinical practice
      and reach a different diagnosis due to its non-specific signs and symptoms. Four
      patients with signs and symptoms suggestive of TA-GVHD were evaluated and the
      literature reviewed. The transfusion history was of great importance, as was the
      exclusion of other conditions that may present with similar signs and symptoms
      (fever, skin rash, diarrhea, pancytopenia, icterus and renal failure).
      Confirmation of TA-GVHD was by skin biopsy. TA-GVHD must be considered as a
      differential diagnosis in patients who present with fever, pancytopenia,
      diarrhea, skin rash and icterus, and the transfusion history must be questioned.
      Mortality is very high despite various therapeutic approaches. This makes
      prophylaxis essential. TA-GVHD can be prevented by irradiation of blood products
      and by avoiding the use of blood transfusions from family donors.

PMID- 16618444
TI  - Glucose production in the human placenta.
AB  - Glucose transfer from mother to fetus by placental facilitated diffusion is the
      dominant mechanism by which the fetus acquires glucose. In small for gestational
      age pregnancies, fetal glucose concentrations tend to be lower than normal and
      this persists following delivery. GLUT1 is the major glucose transporter in human
      placenta but there is no evidence of GLUT1 deficiency as a cause of the lower
      fetal glucose concentration in small for gestational age pregnancy. The
      physiological and pathological roles of the other glucose transporters (and there
      are 14 currently described) are unknown. In recent years, the possibility has
      been raised that the placenta is itself capable of supplying glucose for fetal
      needs. This hypothesis derived from glucose isotope studies in normal pregnancy,
      where dilution of glucose isotope was demonstrated in blood samples taken from
      the fetal circulation during intravenous infusion of glucose isotope in the
      mother. Although other gluconeogenic enzymes were known to be present, the
      placenta was previously considered incapable of glucose secretion because it
      lacked functional glucose-6-phosphatase. Recent studies, however, have suggested
      that specific glucose-6-phosphatase may be present in placenta but it may be the
      product of a different gene from conventional hepatic glucose-6-phosphatase. The
      presence of the specific transporters necessary for glucose-6-phosphatase
      activity is currently being investigated. The role of placental glucose secretion
      in normal and growth-restricted pregnancies is an area of current study.

PMID- 16618446
TI  - Genetic background of acute coronary syndromes.
AB  - Acute coronary syndromes (ACS) are one of the major causes of mortality nowadays.
      Although much is known about factors involved in atherogenesis and acute coronary
      events, there are still many cases in which a lack of classical risk factors,
      together with family history, suggests the presence of an unrevealed genetic
      predisposition and molecular mechanisms. This paper reviews genetic
      predisposition to ACS. It also indicates which genes are linked to the processes
      of destabilization and rupture of atherosclerotic plaque and thus may be
      potential targets for more effective prophylaxis and treatment.

PMID- 16618447
TI  - Promising new therapies for Behcet's disease.
AB  - Improved understanding of the pathogenic mechanisms of Behcet's disease (BD), and
      especially of the molecular basis involved in its pathogenesis, has sparked a new
      generation of potential BD treatments with improved side effect profiles and/or
      more specific targeting of the immune system. These therapies include new
      immunosuppressants, biologic medications, tolerizing agents, and immunoablation
      techniques, a number of which are currently in use in clinical practice
      (interferons). While some of these new therapies target specific inflammatory
      mechanisms in SLE (tumor necrosis factor-alpha inhibitors), others work by non
      specific inhibition of the immune system (immunoablation). Each of these
      approaches will be discussed in this review.

PMID- 16618448
TI  - Characteristics of Castleman's disease in Peru.
AB  - BACKGROUND: Castleman's disease (CD) is a very rare disorder of unknown etiology
      that is characterized by masses of lymphoid tissue. METHODS: The records of all
      patients with a histological diagnosis of CD who were seen at the Hospital
      Nacional Cayetano Heredia and the Instituto Nacional de Enfermedades Neoplasicas
      between 1985 and 2003 and 1985 and 2001, respectively, were reviewed. RESULTS:
      The study included 10 patients. The age of onset ranged from 5 to 65 years. Nine
      patients met the criteria for localized CD; six of them were asymptomatic. The
      most common sites of presentation were the cervical lymph nodes (n=5), submaxilar
      lymph nodes (n=2), parotid gland (n=1), and lung (n=1). Eight patients had
      histological evidence of the hyaline-vascular variant and one had the plasma-cell
      variant. The primary treatment was complete surgical resection. One patient met
      the criteria for multicentric CD; he was asymptomatic, had histological evidence
      of the plasma-cell variant, and was treated with combination chemotherapy. All
      ten patients are currently alive with no evidence of recurrence. CONCLUSION: The
      localized form of CD presents as progressive, painless, slow-growing lymph node
      enlargement that is generally asymptomatic. The locations most commonly involved
      in the localized form are the cervical lymph nodes, followed by the submaxillary
      lymph nodes, where it poses a diagnostic challenge to the clinician because it
      tends to mimic other head and neck diseases. Localized CD is almost always of the
      hyaline-vascular variant and complete surgical excision of the tumor allows full
      recovery in all cases.

PMID- 16618449
TI  - Reflux esophagitis in patients with partial gastrectomy and Billroth I or II
      reconstruction.
AB  - BACKGROUND: Data on the occurrence of reflux esophagitis and Barrett's esophagus
      in patients with Billroth I or II resection is sparse. For this reason a cross
      sectional study was done in order to assess reflux disease in Billroth resection.
      METHODS: Consecutive patients were included in the study. Coincidental pathology
      (hiatus hernia, ulcer, esophagitis, and cancer) was noted. RESULTS: Over a period
      of 12 years, 370 consecutive patients with a partial gastrectomy were seen (268
      Billroth II, 102 Billroth I) and three groups of patients were identified. Group
      1 included 64 patients (17%) with a hiatus hernia; group 2, 16 patients (4%) with
      reflux esophagitis; and group 3, 290 patients (78%) with only a Billroth
      resection. Reflux disease occurred significantly more often in men than in women
      (7.5% vs. 2%, p<0.05). There was no difference in type of resection or in the
      presence of reflux esophagitis. Four patients had an esophageal cancer (only one
      adenocarcinoma). CONCLUSION: Only a minority of patients with partial gastrectomy
      has signs of esophagitis in the long term.

PMID- 16618450
TI  - Anemia in new-onset congestive heart failure inpatients admitted for acute
      decompensation.
AB  - BACKGROUND: Anemia may have important deleterious effects on patients with heart
      failure. We investigated the presence and causes of anemia among patients
      admitted because of new-onset congestive heart failure. The prognostic value of
      anemia was also evaluated. METHODS: We evaluated the presence of anemia, which
      was defined as hemoglobin concentrations lower than 13g/dl in men and lower than
      12g/dl in women. One-year mortality and hospital readmission rates were also
      studied. RESULTS: A total of 103patients were included in the study. Their mean
      age was 78.5years and 53% were women. Mean hemoglobin levels were 12.4g/l. Forty
      four patients (43%) had anemia at the time of hospital admission, 34 of them had
      true anemia and 10spurious anemia caused by hemodilution. Patients taking
      preadmission angiotensin-converting enzyme inhibitors had more severe anemia than
      those not taking them (p<0.01). The presence of anemia was not associated with an
      increase in mortality (p=0.3) or in readmission rates (p=0.1) after 1year of
      follow-up. CONCLUSIONS: Anemia is frequent in new-onset heart failure patients
      admitted for acute decompensation. However, the presence of anemia does not seem
      to be related to an increase in mortality or readmission in this small cohort.

PMID- 16618451
TI  - Enterobacter sakazakii in the mouths of stroke patients and its association with
      aspiration pneumonia.
AB  - BACKGROUND: Previous studies by our group have identified a high prevalence of
      Gram-negative bacilli in the mouths of stroke patients. Eradication of such
      organisms by selective decontamination of the digestive tract (SDD) has not
      previously been studied. Enterobacter sakazakii is a rarely found organism that
      has previously been identified as a cause of neonatal meningitis and sepsis but
      that has rarely been reported as a pathogen in older people. The purpose of this
      study was to look specifically for E. sakazakii in the mouths of stroke patients
      and to correlate its isolation with response to SDD gel and the presence of
      clinical complications such as pneumonia. METHODS: Following an acute stroke, 203
      patients were recruited for the study and received placebo or SDD in a 50:50
      ratio. Oral swabs were obtained on nine separate occasions and E. sakazakii was
      cultured from them. Clinical data were prospectively collected and analysed.
      RESULTS: E. sakazakii was identified in 7 of 203 patients. The organism was
      almost exclusively removed by SDD gel, but in those patients in whom an abnormal
      swallow was present, pneumonia was found in two of the four cases. CONCLUSION: E.
      sakazakii may colonise the mouths of acute stroke patients. Since SDD gel is not
      routinely administered to such patients, this organism may be implicated in
      patients who subsequently develop aspiration pneumonia.

PMID- 16618452
TI  - Are malnourished patients complex patients? Health status and care complexity of
      malnourished patients detected by the Short Nutritional Assessment Questionnaire
      (SNAQ).
AB  - BACKGROUND: This article describes the characteristics of patients identified as
      malnourished using the Short Nutritional Assessment Questionnaire (SNAQ) in terms
      of health status (quality of life, functional capacity, and body composition) and
      care complexity. We expected that by using the quick and easy SNAQ method of
      screening on malnutrition, inferences could be made about general health status
      and care complexity. This information can be used for optimal multi-disciplinary
      treatment of the malnourished patient. METHODS: The research population consisted
      of a group of 588 patients admitted to internal medicine and surgery wards of the
      VU university medical center. Patients with a SNAQ score of at least 3 points
      were considered malnourished. The SNAQ score was compared to the health status,
      which was determined by serum albumin, hand grip strength, quality of life, body
      composition, and estimated care complexity. RESULTS: At admission, 172 patients
      (29%) had a SNAQ score of at least 3 points. These patients had a significantly
      poorer quality of life, poorer physical functioning, a lower fat free mass index,
      and higher care complexity. CONCLUSION: These findings confirm our assumption
      that a considerable proportion of malnourished patients should be considered as
      complex patients and that malnutrition is an important aspect and indicator of
      overall health status of the patients. The SNAQ is a simple malnutrition
      screening tool, applicable in the current complex hospital situation, to identify
      these complex, malnourished patients.

PMID- 16618453
TI  - Burnout in internal medicine physicians: Differences between residents and
      specialists.
AB  - BACKGROUND: Burnout poses a substantial problem for physicians' well-being and
      for the quality of health care. The role of workload in comparison to subjective
      work characteristics has been rarely studied. The purpose of this study was to
      explore the associations of burnout with workload and subjective work
      characteristics in internal medicine specialists and residents. METHODS: A cross
      sectional study using an anonymous mailed survey was used. Some 103 specialists
      and 143 residents participated in the study. Burnout was measured using the
      Maslach Burnout Inventory. Subjective work characteristics included perceived job
      demands in terms of time pressure, mental effort and emotional labor. Workload
      was assessed in terms of average number of hours worked per week. RESULTS:
      Emotional exhaustion in medical specialists was only predicted by perceived job
      demands [odds ratio 3.7 (CI 1.7-7.9), P<0.001]. Emotional exhaustion in medical
      residents was only predicted by emotional labor [odds ratio 1.9 (CI 1.2-3.0),
      P=0.003]. Depersonalization among medical specialists was only predicted by
      emotional labor [odds ratio 2.7 (CI 1.1-6.7), P=0.032], while depersonalization
      among medical residents was only predicted by number of hours worked per week
      [odds ratio 1.1 (CI 1.1-1.2), P=0.007]. DISCUSSION: Perceived working conditions
      were more important than workload in explaining the variance in burnout. In
      addition, burnout in medical specialists and residents was linked to different
      characteristics of their working environment.

PMID- 16618454
TI  - The effect of prednisolone on serum sodium concentration.
AB  - BACKGROUND: Glucocorticoids are widely used in clinical practice. In addition to
      their anti-inflammatory effects, they influence the salt and water homeostasis.
      Although parts of the latter action have been studied individually, there are no
      reports in stable outpatients on the net effect of glucocorticoids on serum
      sodium concentration. METHODS: A group of 23 patients on chronic prednisolone
      therapy was compared with a control population with respect to serum sodium
      concentration. Intra-individual changes in serum sodium concentration after the
      initiation of prednisolone therapy were studied separately in 14 patients.
      RESULTS: A significantly higher serum sodium level of 1.67mmol/L (P=0.03) was
      observed in the prednisolone-treated patients, whereas initiation of prednisolone
      was accompanied by an increase of 2.61mmol/L (P=0.004). The doses and duration of
      prednisolone therapy had no relation to the increase in serum sodium
      concentration. CONCLUSION: Prednisolone therapy in stable outpatients results in
      a small, yet significant, increase in serum sodium concentration.

PMID- 16618455
TI  - Cervical spondylitis due to Neisseria meningitidis.
AB  - The diverse clinical spectrum of meningococcal infections includes frequent
      clinical forms, such as meningitis or septicemia, and uncommon manifestations,
      such as septic arthritis. Neisseria meningitidis is not generally considered to
      be a causative agent of osteoarticular infections. We report the first case of
      acute primary cervical spondylitis in a 48-year-old man.

PMID- 16618456
TI  - Severe hypercalcemia as a presenting sign of systemic lupus erythematosus.
AB  - The association of hypercalcemia and systemic lupus erythematosus is quite
      uncommon, with only three cases having been reported in the literature. We
      present a case in which this association is highlighted and demonstrate the
      presumed mechanism of high calcium level and the usefulness of early diagnosis
      and aggressive treatment.

PMID- 16618457
TI  - Pacemaker lead infection caused by Aspergillus fumigatus.
AB  - We report a case of pacemaker lead infection caused by Aspergillus fumigatus that
      was successfully treated by surgery and with voriconazole. This infection is rare
      and dangerous. When it is suspected, transesophageal echocardiography should be
      performed to look for lead-attached vegetations and the entire pacing system
      should be removed.

PMID- 16618458
TI  - Warfarin-induced gastric bleeding and intestinal obstruction.
AB  - Oral anticoagulant therapy with warfarin is commonly used to prevent
      thromboembolic events in patients at risk. The degree of anticoagulation is
      variable among individuals and is influenced by many factors; therefore, patients
      must be monitored frequently to assess potential adverse effects related to
      treatment. There is a direct relationship between excessive anticoagulation and
      the risk of bleeding. We present a patient who came in with an acute abdomen,
      anemia, and increased international normalized ratio. Gastroscopy revealed a
      large amount of blood in the stomach. Hemodynamic instability necessitated urgent
      laparotomy. The small bowel was found to be ischemic due to increased
      intraluminal pressure. Upon enterotomy, liters of old hematoma were evacuated and
      the intestine resumed its blood supply. To our knowledge, we describe the first
      reported case of intraluminal hematoma as a rare cause of obstructive mechanical
      ileus during warfarin treatment. This case highlights an unknown, but potentially
      lethal, manifestation of warfarin therapy.

PMID- 16618459
TI  - Helicobacter heilmanii gastritis in polymyositis.
AB  - We report the original case of a patient with polymyositis (PM) who developed
      severe gastritis related to Helicobacter heilmanii. H. heilmanii eradication,
      using triple therapy with omeprazole, metronidazole and amoxicillin, resulted in
      the complete disappearance of digestive manifestations. As an association has
      been found between gastric adenocarcinoma/MALT lymphoma and both
      polymyositis/dermatomyositis (PM/DM) and H. heilmanii infection, respectively, we
      suspect that PM/DM patients who develop H. heilmanii infection may have a higher
      risk of gastric malignancy occurrence. Further studies are warranted to confirm
      whether Helicobacter species infections do, in fact, increase the risk of gastric
      adenocarcinoma/MALT lymphoma in patients with PM/DM.

PMID- 16618460
TI  - Hypersersensitivity and Kounis syndrome due to a viper bite.
AB  - A 60-year-old male was bitten by a venomous snake (Vipera ammodytes) and
      gradually developed signs of an allergic reaction including generalized itching,
      generalized rash, and chest discomfort. This was followed by severe retrosternal
      pain with electrocardiographic evidence of an inferior myocardial ischemia
      progressing to acute myocardial infarction. Cardiac enzymes and troponin, serum
      tryptase, and histamine were elevated. Coronary arteriography showed normal
      coronary arteries. This is a characteristic type I variant of Kounis syndrome,
      which is the concurrence of acute coronary syndromes with conditions associated
      with mast cell activation including allergic or hypersensitivity reactions as
      well as anaphylactic or anaphylactoid reactions. This is the first report to show
      that viper bites can induce allergic angina and/or allergic myocardial
      infarction.

PMID- 16618461
TI  - Acute interstitial nephritis associated with salmonellosis.
AB  - Acute interstitial nephritis (AIN) is a common cause of acute renal failure. We
      report a case of AIN, confirmed by renal biopsy, that developed in a patient with
      typhoid fever due to a Salmonella hadar infection. AIN secondary to Salmonella
      infection is a rare complication that has only been described twice in the
      literature. Salmonella should be added to the list of possible causes of AIN.

PMID- 16618462
TI  - Rhabdomyolysis disclosing hypothyroidism.

PMID- 16618463
TI  - Transient left ventricular systolic dysfunction in a quadriplegic patient.

PMID- 16618464
TI  - Hepatocellular carcinoma presenting with pleuritic pain.

PMID- 16618465
TI  - Increased 18F fluorodeoxyglucose uptake of a vertebral hemangioma responsible for
      oncogenic osteomalacia.

PMID- 16618466
TI  - Opioid prescriptions by U.S. primary care physicians from 1992 to 2001.
AB  - Little is known about primary care physicians' (PCPs) prescribing of opioids. We
      describe trends and factors associated with opioid prescribing during PCP visits
      over the past decade. Using the National Ambulatory Medical Care Survey, we found
      an opioid prescribed in 2,206 (5%) PCP visits from 1992 to 2001. The prevalence
      of visits where an opioid was prescribed increased from a low of 41 per 1000
      visits in 1992-1993 to a peak of 63 per 1000 in 1998-1999 (P < .0001 for trend)
      and then stabilized (59 per 1000 in 2000-2001). Several factors increased the
      odds of receiving an opioid: having Medicaid (odds ratio [OR] 2.09 [95%
      confidence interval (CI) 1.82-2.40]) or Medicare (OR 2.00 [95% CI 1.68-2.39]);
      having a visit between 15 and 35 minutes (OR 1.16 [95% CI 1.05-1.27]); and
      receiving an NSAID (OR 2.27 [95% CI 2.04-2.53]). Patients of hispanic (OR .67
      [95% CI .56-.81]) or other race/ethnicity (OR .68 [95% CI .52-.90]), patients in
      health maintenance organizations (OR .74 [95% CI .66-.84]), and those living in
      the northeast (OR .60 [95% CI .51-.69]) or midwest (OR .75 [95% CI .66-.85]) had
      lower odds of receiving an opioid. Substantial variation exists in opioid
      prescribing by PCPs. Now that pain management standards are advocated,
      understanding the dynamics of opioid prescribing is necessary. PERSPECTIVE: This
      study describes a decade-long increase in opioid prescribing by U.S. primary care
      physicians and identifies important geographic-, racial/ethnic-, and insurance
      related differences in who receives these medications. Several underlying
      factors, including regulatory and legal pressures, attitudes and knowledge of
      opioids, and publicized opioid-related events, may contribute to these
      differences.

PMID- 16618467
TI  - The relationship between maternal chronic pain and child adjustment: the role of
      parenting as a mediator.
AB  - The role of parenting in the relationship between maternal chronic pain and
      negative child outcomes, including internalizing, externalizing, and social and
      health problems, was investigated. Parenting strategies used by mothers with
      chronic pain were compared to parenting strategies used by a control group of
      mothers without pain. Thirty-nine mothers experiencing chronic pain, their 55
      children, 35 pain-free mothers, and their 48 children participated in the study.
      The results showed that for mothers with chronic pain, dysfunctional parenting
      strategies and the quality of the mother-child relationship were related to
      negative child outcomes. Mothers with chronic pain were more likely to engage in
      lax parenting and report reduced relationship quality with children than were
      control mothers. For the chronic pain group, over-reactive parenting was found to
      mediate the relationship between maternal physical functioning and child
      adjustment. Dysfunctional parenting strategies may constitute part of the risk
      that maternal chronic pain poses for children. The similarities between the
      impact of maternal chronic pain on child adjustment and that of other maternal
      stressors, such as depression, are discussed. PERSPECTIVE: In mothers with
      chronic pain, poor maternal physical functioning was associated with increased
      maternal over-reactive behavior that was in turn related to poor child
      adjustment. Maternal over-reactive behavior did not, however, differ in chronic
      pain and control mothers.

PMID- 16618468
TI  - Psychosocial risks for disability in children with chronic back pain.
AB  - Psychosocial factors related to disability in adults with chronic back pain have
      been well studied, but little is known about factors associated with functional
      impairment in pediatric patients with chronic back pain. The purpose of this
      study was to examine whether 2 potential risk factors-use of catastrophizing as a
      coping technique and presence of a familial pain history-were associated with
      disability in pediatric back pain patients. Participants were 65 patients (ages 8
      18) with chronic back pain seen at a multidisciplinary pain clinic. Patients
      completed measures of pain (visual analog scales), disability (Functional
      Disability Inventory), and catastrophizing (Internalizing/Catastrophizing
      subscale of the Pain Coping Questionnaire). Parents provided demographic
      information and familial pain history. Patients reported that chronic back pain
      caused disruptions in their daily functioning and they missed, on average, 2.5
      days of school every month. Catastrophizing and familial chronic pain history
      both were significantly associated with greater disability, with use of
      catastrophizing being the stronger predictor of disability. This study presents
      important findings on potential psychosocial risk factors of functional
      disability in children and adolescents with chronic back pain. Future research
      might clarify mechanisms by which such coping styles are developed and explore
      how familial communication about pain might influence a child's coping ability.
      PERSPECTIVE: Pediatric patients seeking treatment for chronic back pain often
      present with substantial functional impairment that is not well explained by
      disease variables or pain intensity. Two important psychosocial variables
      (catastrophizing and familial pain history) may provide a context for a better
      understanding of pain-related disability in children.

PMID- 16618469
TI  - Validating the use of two-item measures of pain beliefs and coping strategies for
      a veteran population.
AB  - Previous research has demonstrated that 2-item versions of subscales from the
      Chronic Pain Coping Inventory, Coping Strategy Questionnaire, and the Survey of
      Pain Attitudes appear adequately reliable and valid for use in studies with large
      sample sizes. It was suggested that use of the abbreviated scales might help to
      expand the testing and application of cognitive-behavioral models of pain to new
      settings and with new populations where assessment burden might be a key issue.
      This study explored the utility of these brief scales among veterans in a
      Veterans Affairs setting. Strong associations were found between the 2-item
      versions and their respective parent scales. In addition, the 2-item scales were
      found to be associated with other pain-related measures, supporting their
      predictive validity. The results of this study replicate previous findings and
      offer support for the use of the 2-item versions for both screening and research
      purposes in Veterans Affairs settings with a veteran population. PERSPECTIVE:
      This article presents the psychometric properties of brief versions of 3 commonly
      used pain coping and belief questionnaires in a unique population. These measures
      could be used clinically for initial screening purposes, as well as for treatment
      monitoring.

PMID- 16618470
TI  - Reduction of pain catastrophizing mediates the outcome of both physical and
      cognitive-behavioral treatment in chronic low back pain.
AB  - The aim of this study was to examine whether treatments based on different
      theories change pain catastrophizing and internal control of pain, and whether
      changes in these factors mediate treatment outcome. Participants were 211
      patients with nonspecific chronic low back pain (CLBP) participating in a
      randomized controlled trial, attending active physical treatment (APT, n = 52),
      cognitive-behavioral treatment (CBT, n = 55), treatment combining the APT and CBT
      (CT, n = 55), or waiting list (WL, n = 49). Pain catastrophizing decreased in all
      3 active treatment groups and not in the WL. There was no difference in the
      change in internal control across all 4 groups. In all the active treatment
      groups, patients improved regarding perceived disability, main complaints, and
      current pain at post-treatment, and no changes were observed in the WL group.
      Depression only changed significantly in the APT group. Change in pain
      catastrophizing mediated the reduction of disability, main complaints, and pain
      intensity. In the APT condition, pain catastrophizing also mediated the reduction
      of depression. Not only cognitive-behavioral treatments but also a physical
      treatment produced changes in pain catastrophizing that seemed to mediate the
      outcome of the treatment significantly. The implications and limitations of these
      results are discussed. PERSPECTIVE: This article shows that treatment elements
      that do not deliberately target cognitive factors can reduce pain
      catastrophizing. Reduction in pain catastrophizing seemed to mediate the
      improvement of functioning in patients with chronic low back pain. The results
      might contribute to the development of more effective interventions.

PMID- 16618471
TI  - Using the American Pain Society's patient outcome questionnaire to evaluate the
      quality of postoperative pain management in a sample of Norwegian patients.
AB  - In the United States, quality improvement (QI) approaches have been used to
      evaluate pain management. However, the use of QI approaches to evaluate the
      quality of patient care is just emerging in many European countries. The purposes
      of this study, using the American Pain Society's QI Standards, were: to describe
      changes over time, in pain severity, in pain interference with function, and in
      the doses of analgesics administered; to describe patients' level of satisfaction
      with postoperative pain management; and to determine the relationships between
      pain severity and patient outcomes. Results from a sample of patients who
      underwent orthopedic surgery suggest that undertreatment of pain persists across
      the first 5 postoperative days and that pain's level of interference with
      function decreases significantly between the third and fifth postoperative days.
      As in other studies, despite high pain intensity scores, patients reported high
      levels of satisfaction with postoperative pain management. PERSPECTIVE: Findings
      suggest that the undertreatment of pain results in significant decrements in
      function over the first 5 postoperative days. Future studies designed to improve
      the quality of postoperative pain management need to use multimodal approaches
      and evaluate not only pain intensity, but improvements in function as critical
      outcome measures.

PMID- 16618472
TI  - The epidemiology of chronic pain of predominantly neuropathic origin. Results
      from a general population survey.
AB  - Progress in the understanding of chronic pain with neuropathic features has been
      hindered by a lack of epidemiologic research in the general population. The Leeds
      Assessment of Neuropathic Symptoms and Signs score (S-LANSS) was recently
      validated for use in postal surveys, making the identification of pain of
      predominantly neuropathic origin possible. Six family practices in 3 UK cities
      (Aberdeen, Leeds, and London) generated a total random sample of 6,000 adults.
      The mailed questionnaire included demographic items, chronic pain identification,
      and intensity questions, the S-LANSS, the Level of Expressed Needs questionnaire,
      and the Neuropathic Pain Scale. With a corrected response rate of 52%, the
      prevalence of any chronic pain was 48% and the prevalence of pain of
      predominantly neuropathic origin was 8%. Respondents with this chronic
      neuropathic pain were significantly more likely to be female, slightly older, no
      longer married, living in council rented accommodation, unable to work, have no
      educational qualifications, and be smokers than all other respondents. Multiple
      logistic regression modeling found that pain of predominantly neuropathic origin
      was independently associated with older age, gender, employment (being unable to
      work), and lower educational attainment. Respondents with this pain type also
      reported significantly greater pain intensity, higher scores on the NPS, higher
      levels of expressed need, and longer duration of pain. This is the first estimate
      of the prevalence and distribution of pain of predominantly neuropathic origin in
      the general population, using a previously validated and reliable data collection
      instrument. PERSPECTIVE: Chronic pain with neuropathic features appears to be
      more common in the general population than previously suggested. This type of
      pain is more severe than other chronic pain but distributed similarly throughout
      sociodemographic groups.

PMID- 16618473
TI  - The prevalence and occurrence of diabetic foot ulcer pain and its impact on
      health-related quality of life.
AB  - This study describes the prevalence and occurrence of diabetic foot ulcer (DFU)
      pain and the impact of DFU pain on health-related quality of life (HRQL) using
      generic and disease specific instruments. Data were obtained from 127 patients
      with DFU who were recruited from 6 hospital-based diabetic outpatient clinics.
      HRQL was measured using the Medical Outcome Study-Short Form (SF-36) and the
      Diabetes Foot Ulcer Scale (DFS). Occurrence of pain was assessed using 2 items
      from the DFS (ie, pain while walking and/or standing and pain during the night
      related to foot ulcer problems). Seventy-five percent reported some pain related
      to DFU and 57% reported DFU pain while walking and/or standing and also during
      the night. Twenty-five percent reported pain none of the time. A higher
      percentage of patients with pain reported having a prescription for an analgesic
      medication than those without pain. Patients who reported pain most or all of the
      time had statistically and clinically significantly poorer HRQL than those who
      did not report pain. These findings suggest that pain associated with DFU is a
      significant clinical problem. Additional research is warranted to further
      characterize the pain associated with DFU and its impact on patient outcomes and
      HRQL. PERSPECTIVE: Numerous basic and clinical studies have focused on pain
      associated with diabetic peripheral neuropathy. Findings from this study suggest
      a new pain problem in patients with diabetes, namely, pain associated with foot
      ulcers, that warrants further investigation.

PMID- 16618474
TI  - Look what you've been missing.

PMID- 16618475
TI  - Letter to the editor: Practicing under the influence of fatigue.

PMID- 16618476
TI  - Invasive fungal infections caused by Candida and Malassezia species in the
      neonatal intensive care unit.
AB  - Premature infants in the neonatal intensive care unit (NICU) are at particular
      risk of invasive fungal infections, and unfortunately, the incidence of fungal
      septicemia appears to be increasing. Invasive infections caused by species of
      Candida or Malassezia have been documented in the NICU and are often associated
      with significant morbidity and mortality. Controversies regarding the diagnosis,
      treatment, and prevention of such diseases exist. The purpose of this review is
      to describe the epidemiology, clinical manifestations, diagnostic techniques,
      treatment, and prevention of invasive infection due to Candida and Malassezia
      species in the neonatal intensive care setting.

PMID- 16618477
TI  - A model of nursing care microsystems for a large neonatal intensive care unit.
AB  - Nationally the number and size of neonatal intensive care units (NICUs) continues
      to grow. Today, NICUs with >40 beds, often referred to as "megaunits," are not
      uncommon. Staff in large units find it challenging to maintain teamwork,
      communication, and continuity of nursing care for patients. Families find large
      units overwhelming. In large NICUs, nurse leaders struggle to achieve a balance
      between parent satisfaction with care provided and nursing job satisfaction. This
      article describes the development of a new model of nursing practice, a nursing
      team microsystem. This innovative model has the unique effect of creating smaller
      units within the larger one, using highly skilled nursing teams, that are
      geographically grouped to provide care for infants and their families. The model
      supports teamwork, communication, continuity of care, and has shown a positive
      impact on both family and nurses' job satisfaction.

PMID- 16618478
TI  - A phase 1 trial testing an enteral solution patterned after human amniotic fluid
      to treat feeding intolerance.
AB  - OBJECTIVE: Feeding intolerance is a common problem in neonates; in some cases it
      may be related to atrophic changes in the small bowel mucosa. In these infants,
      feeding tolerance might improve after oral administration of enterocyte growth
      factors in a sterile, isotonic, noncaloric solution patterned after human
      amniotic fluid. STUDY DESIGN: Ten infants who met the study criteria for feeding
      intolerance were enrolled in this pilot trial. The test solution was
      administered, 2.5 mL/kg every 3 hours, until 80 mL/kg/day of milk feedings were
      tolerated, or for a maximum of 7 days. When milk feedings were prescribed, they
      were mixed with the test solution. Volumes of milk feedings were increased in
      amounts determined by the attending neonatologist and neonatal nurse
      practitioner. The outcome was the net average enteral kilocalories per kilogram
      of body weight per day (kcal/kg/day) for 3 periods: (1) the 3 days before the
      test treatment was begun, (2) the days the test treatment was administered, and
      (3) the 7 days following cessation of the test treatment. RESULTS: At study entry
      the infants' chronological ages ranged from 3 to 65 days. All infants tolerated
      the test solution, which was given for a mean of 5 days (range 3 to 7 days).
      During that period, the infants received more enteral calories (mean 18
      kcal/kg/day, range 1 to 32) than during the preceding 3 day period (mean 3
      kcal/kg/day, range 0 to 7, P < 0.05). During the 7 days following the test
      treatment the infants received 87 enteral kcal/kg/day (range 11 to 109, P < 0.02
      compared to the treatment period). CONCLUSIONS: In this Phase 1 pilot trial, 10
      heterogeneous infants in the neonatal intensive care unit with feeding
      intolerance had a significant increase in milk feedings after treatment with a
      sterile, isotonic, noncaloric solution patterned after human amniotic fluid.

PMID- 16618479
TI  - Synthesis of polyhydroxy amino acids based on D- and L-alanine from D-glycero-D
      gulo-heptono-1,4-lactone.
AB  - 2-Amino-2,3-dideoxy-D-manno-heptonic acid (7) has been synthesized from 2,5,6,7
      tetra-O-acetyl-3-deoxy-D-gluco-heptono-1,4-lactone (1), which was readily
      prepared from D-glycero-D-gulo-heptono-1,4-lactone. O-Deacetylation of 1 followed
      by treatment with 13:1 (v/v) 2,2-dimethoxypropane/acetone in the presence of p
      toluenesulfonic acid gave methyl 3-deoxy-4,5:6,7-di-O-isopropylidene-D-gluco
      heptonate (3) as a crystalline product (80% yield). The free hydroxyl group (OH
      2) of 3 was mesylated and substituted by azide to give the corresponding azide
      derivative 5. Hydrogenolysis and further hydrolysis of the ester function of 5
      afforded alpha-amino acid 7 (43% overall yield from 1). Compound 7 is an analog
      of L-alanine having a polyhydroxy chain attached to C-3. The diastereoisomer of 7
      at C-2, 2-amino-2,3-dideoxy-D-gluco-heptonic acid (12) was also prepared from 3,
      by a route that involved 2,3-dideoxy-2-iodo derivative 8 as a key intermediate.

PMID- 16618480
TI  - Structural heterogeneity of wheat arabinoxylans revealed by Raman spectroscopy.
AB  - A set of arabinoxylan samples differing in their arabinose composition and
      various samples of arabino-xylo-oligosaccharide samples were analysed by Raman
      spectroscopy. Specific signatures for arabinose substitution were found in
      several spectral regions, that is, 400-600, 800-950 and 1030-1100 cm(-1). A
      linear relationship was observed between the peak ratio 855/895 cm(-1) of the
      second derivative spectra and the A/X ratio determined by chemical analysis.
      Moreover, spectral changes were observed in the 400-600 cm(-1) region assigned to
      the coupled vibrations mode in the skeleton: while the intensity of the band at
      570 cm(-1) increased with the degree of substitution, that at 494 cm(-1)
      decreased. Similarly, a linear relationship was observed between the peak
      intensity ratio 570/494 cm(-1) calculated on the second derivative spectra and
      the composition data. Analysis of Raman spectra of arabino-xylo-oligosaccharides
      allowed to identify specific spectral features of disubstitution.

PMID- 16618482
TI  - Simulations of infectious diseases on networks.
AB  - This paper examines the spread of diseases within populations in the context of
      networks of potentially disease-causing contacts. We examine the assumptions
      underlying classical mathematical models of epidemics and how more realistic
      assumptions can be made using contact networks. Several well-known kinds of
      contact networks are examined and simulated by evaluating their structural
      properties relevant to disease propagation. Algorithms used in the study of these
      networks are explained and numerical simulations of percolation and the epidemic
      process carried out to explore the effects that the network structure has on
      disease progression.

PMID- 16618481
TI  - Monoglycosyl, diglycosyl, and dinucleoside methylenediphosphonates: direct
      synthesis and antiviral activity.
AB  - A direct and general access to D-glycosyl 3-, 5-, or 6-methylenediphosphonates,
      di-D-glycosyl 1,5-, 3,5-, 3,6-, 5,5-, or 6,6-methylenediphosphonates and
      dithymidine 3',5'-methylenediphosphonate is described. The method involves the
      one-pot alkylidenediphosphorylation of glycosyl or thymidine derivatives. No
      antiviral activity was detected against a panel of RNA and DNA viruses.

PMID- 16618483
TI  - Estimating the effect of air pollution from a coal-fired power station on the
      development of children's pulmonary function.
AB  - Using geographical information systems (GIS) tools, the present study analyzed
      the association between children's lung function development and their long-term
      exposure to air pollution. The study covered the cohort of 1492 schoolchildren
      living in the vicinity of a major coal-fired power station in the Hadera sub
      district of Israel. In 1996 and 1999, the children underwent subsequent pulmonary
      function tests (PFT) (forced vital capacity (FVC) and forced expiratory volume
      during the first second (FEV(1))), and the children's parents completed a
      detailed questionnaire on their health status and household characteristics. A
      negative association was found between changes in the results of PFT and the
      estimated individual levels of air pollution. A sensitivity test revealed a
      FEV(1) decline from -4.3% for the average pollution level to -10.2% for the high
      air pollution level. The results of a sensitivity test for FVC were found to be
      similar. Association with the reported health status was found to be
      insignificant. As we conclude, air pollution from a coal-fired power station,
      although not exceeding local pollution standards, had a negative effect on
      children's lung function development. As argued, previous studies carried out in
      the region failed to show the above association because they were based on zone
      approaches that assign average concentration levels of air pollutants to all
      individuals in each zone, leading to a misclassification bias of individual
      exposure.

PMID- 16618484
TI  - Importance of extracardiac alpha1-adrenoceptor stimulation in assisting
      dofetilide to induce torsade de pointes in rabbit hearts.
AB  - In anaesthetized rabbits, alpha(1)-adrenoceptor stimulation increases the
      propensity of repolarization-prolonging drugs to induce torsade de pointes
      ventricular tachycardia. However, it is not known whether the stimulation of
      intracardiac alpha(1)-adrenoceptors, or the increased ventricular stretch caused
      by extracardiac alpha(1)-adrenoceptor-mediated peripheral vasoconstriction and
      increased resistance, are the sensitizing factors. Accordingly, this study
      investigated whether a sustained load-induced left ventricular stretch or
      stimulation of the intracardiac alpha(1)-adrenoceptors with 100 nM methoxamine,
      or the co-application of these two, can assist dofetilide (100 nM) to elicit
      torsade de pointes in isolated Langendorff-perfused, rabbit hearts. In the
      stretched hearts, a constant high level of stretch was produced by a water-filled
      left ventricular balloon inflated to a volume of 1.4 ml, whereby the systolic and
      end-diastolic pressures virtually did not exceed the physiological range
      (<or=157+/-11 mm Hg and <or=9+/-2 mm Hg, respectively; mean+/-S.E.M.). Perfusion
      with dofetilide prolonged the QT interval significantly and indifferently in all
      hearts. Neither this stretch nor methoxamine nor the in combination affected the
      QT interval, the heart rate or the coronary flow. Interestingly, neither the
      stretch ('dofetilide+stretch' group, n=8 hearts), nor methoxamine
      ('dofetilide+methoxamine' group, n=8 hearts), nor the in combination
      ('dofetilide+stretch+methoxamine' group, n=8 hearts) elevated the incidence of
      torsade de pointes as compared with the 'dofetilide alone' group (n=9 hearts)
      (0%, 25%, 0%, versus 44%, respectively). In conclusion, neither a sustained load
      induced stretch nor alpha(1)-adrenoceptor stimulation nor the in combination
      assisted dofetilide to induce torsade de pointes in isolated rabbit hearts,
      suggesting the importance of extracardiac alpha(1)-adrenoceptor stimulation in
      this phenomenon.

PMID- 16618485
TI  - The relevance of psychosocial variables and working conditions in predicting
      nurses' coping strategies during the SARS crisis: an online questionnaire survey.
AB  - OBJECTIVES: The purpose of this investigation was to examine the relationship
      between psychosocial variables and working conditions, and nurses' coping methods
      and distress in response to the severe acute respiratory syndrome (SARS) crisis
      in Canada. PARTICIPANTS AND PROCEDURE: The sample consisted of 333 nurses (315
      women, 18 men) who completed an Internet-mediated questionnaire that was posted
      on the Registered Nurses' Association of Ontario (RNAO) website between March and
      May 2004. The questionnaire was restricted to respondents who had to authenticate
      their RNAO membership with a valid username and password before accessing the
      questionnaire. This served a dual purpose: to ensure that only RNAO nurses
      completed the questionnaire and thereby safeguarding the generalizability of the
      findings; and second, to prevent any one nurse from contributing more than once
      to the overall sample. RESULTS: Correlational analysis yielded several
      significant relationships between psychosocial variables and working conditions,
      and the traditional correlates of burnout and stress. Three multiple regression
      analysis revealed that the model we evolved--including higher levels of vigor,
      organizational support, and trust in equipment/infection control initiative; and
      lower levels of contact with SARS patients, and time spent in quarantine-
      predicted to lower levels of avoidance behavior, emotional exhaustion, and state
      anger. CONCLUSIONS: By employing models of stress and burnout that combine
      psychosocial variables and working conditions, researchers can account for
      significant amounts of variance in outcomes related to burnout. These findings
      highlight the importance of vigor and perceived organizational support in
      predicting nurses' symptoms of burnout. For healthcare administrators, this means
      that a likely strategy for assuaging the negative outcomes of stress should
      address nurses' psychosocial concerns and the working conditions that they face
      during novel times of crisis.

PMID- 16618486
TI  - A randomized controlled trial of a nurse short-message service by cellular phone
      for people with diabetes.
AB  - BACKGROUND: Nurse's education using telemedicine results in a decrease in blood
      glucose levels in patients with type 2 diabetes. OBJECTIVE: To investigate the
      effectiveness of an educational intervention that used both the cellular phone
      and the Internet to provide a short-messaging service (SMS) relating to plasma
      glucose levels. METHODS: Twenty-five patients were randomly assigned to an
      intervention group and 26 to a control group. The intervention was applied for 12
      weeks. The goal of the intervention was to keep blood glucose concentrations
      close to the normal range. Patients in the intervention group were asked to
      access a website by using a cellular phone or to wiring the Internet and input
      their blood glucose levels every day. Participants were sent the optimal
      recommendations by both cellular phone and the Internet weekly. RESULTS: Patients
      in the intervention group had a mean decrease in glycosylated haemoglobin
      (HbA(1)c) levels of 1.15% and those in the control group had a mean increase of
      HbA(1)c levels of 0.07% (p=0.005). There was a significant mean change in the
      2hrs post-meal glucose (2HPMG) level for the intervention group (p<0.05), with a
      mean change of -4.7mmol/l. The mean change in the control group was not
      significant. CONCLUSION: This educational intervention using the Internet and an
      SMS by cellular phone improved levels of HbA(1)c and 2HPMG.

PMID- 16618487
TI  - Influence of catheter design on lumen wall temperature distribution in
      intracoronary thermography.
AB  - Intracoronary thermography is a currently used vulnerable plaque detection
      method. We studied how catheter design and catheter location influence the
      temperature readings, and thus its capacity to detect vulnerable plaques. Finite
      element calculations were performed on geometries representing the coronary
      artery, the vulnerable plaque and the catheter. Catheter material, diameter and
      location with respect to the plaque were varied. Both flow and no-flow situations
      were studied. Maximal lumen wall temperature difference without a catheter
      (DeltaT=0.12 degrees C, flow=75 cm(3) min(-1)) was considered the reference.
      Presence of a 1.0mm nitinol catheter right under the plaque increased DeltaT to
      0.14 degrees C, whereas a 1.0 mm polyurethane catheter increased DeltaT to 0.51
      degrees C. The location at which a thermosensitive element should be placed for
      most optimal temperature readings during a pullback was shown to lie at the
      catheter edge for the nitinol catheter and at 1.1mm from the catheter edge for
      the polyurethane catheter. Temperature readings decreased to background
      temperature when the catheter was in close proximity but not overlapping the
      plaque. DeltaT decreased approximately by 70% when a gap of 0.2 mm existed
      between the catheter and the lumen wall. Occlusion of blood flow increased DeltaT
      values in all cases, but most pronounced for nitinol catheters. A polyurethane
      catheter increased the temperature readings, since its heat conductivity is lower
      than that of blood, which makes it a very good choice for heat source detection.
      Catheter design can contribute to enhanced temperature readings and thus can
      enable more optimal vulnerable plaque detection.

PMID- 16618488
TI  - Comparison of 'real-time' and immunometric RT-PCR: RNA interference of reverse
      transcriptase-PCR.
AB  - We measured interleukin-6 (IL-6) mRNA in whole blood, using an immunometric
      reverse transcriptase-polymerase chain reaction (IRT-PCR) method and 'real-time'
      RT-PCR using the Roche LightCycler. Both methods showed similar precision, in
      terms of inter- and intra-assay variation, where a lower total RNA concentration
      was used at a relatively high ratio of (IL-6) mRNA to total RNA. However, the
      'real-time' RT-PCR method showed a greater loss of accuracy at higher
      concentrations of total RNA.

PMID- 16618489
TI  - Mechanisms of black and white stripe pattern formation in the cuticles of insect
      larvae.
AB  - Molecular mechanisms that produce pigment patterns in the insect cuticle were
      studied. Larvae of the armyworm Pseudaletia separata have stripe patterns that
      run longitudinally along the body axis. The pattern in the cuticle became clear
      by being emphasized by the increasing contrast between the black and white colors
      of the lines after the last larval molt. We demonstrated that dopa decarboxylase
      (DDC) mRNA as well as protein are expressed specifically in the epidermal cells
      under the black stripes. The pigmentation on the stripes was clearly diminished
      by injection of a DDC inhibitor (m-hydroxybenzylhydrazine) to penultimate instar
      larvae for 1 day before molting, suggesting that DDC contributes to the
      production of melanin. Further, electron microscopic observation showed that the
      epidermal cells under the gap cuticle region (white stripe) between the black
      stripes contain many uric acid granules, which gives a white color. Our findings
      suggest that the spatially regulated expression of DDC in the epidermal cells
      produces the black stripes while abundant granules of uric acid in the cells
      generate the white stripes in the cuticle. Based on these results, we concluded
      that this heterogeneity in the epidermal cells forms cuticular stripe patterns in
      the armyworm larvae.

PMID- 16618490
TI  - A flexible loop in tyrosine hydroxylase controls coupling of amino acid
      hydroxylation to tetrahydropterin oxidation.
AB  - The role of a polypeptide loop in tyrosine hydroxylase (TyrH) whose homolog in
      phenylalanine hydroxylase (PheH) takes on a different conformation when
      substrates are bound has been studied using site-directed mutagenesis. The loop
      spans positions 177 to 191; alanine was introduced into those positions,
      introducing one alanine substitution per TyrH variant. Mutagenesis of residues in
      the center of the loop resulted in alterations in the KM values for substrates,
      the Vmax value for dihydroxyphenylalanine (DOPA) synthesis, and the coupling of
      tetrahydropterin oxidation to tyrosine hydroxylation. The variant with the most
      altered KM value for 6-methyltetrahydropterin was TyrH F184A. The variants with
      the most affected K(tyr) values were those with substitutions in the center of
      the loop, TyrH K183A, F184A, D185A, P186A and D187A. These five variants also had
      the most reduced Vmax values for DOPA synthesis. Alanine substitution in
      positions 182-186 resulted in lowered ratios of tyrosine hydroxylation to
      tetrahydropterin oxidation. TyrH F184Y and PheH Y138F, variants with the residue
      at the center of the loop substituted with the residue present at the homologous
      position in the other hydroxylase, were also studied. The V/K(tyr) to V/K(phe)
      ratios for these variants were altered significantly, but the results did not
      suggest that F184 of TyrH or Y138 of PheH plays a dominant role in determining
      amino acid substrate specificity.

PMID- 16618491
TI  - Structural classification of small, disulfide-rich protein domains.
AB  - Disulfide-rich domains are small protein domains whose global folds are
      stabilized primarily by the formation of disulfide bonds and, to a much lesser
      extent, by secondary structure and hydrophobic interactions. Disulfide-rich
      domains perform a wide variety of roles functioning as growth factors, toxins,
      enzyme inhibitors, hormones, pheromones, allergens, etc. These domains are
      commonly found both as independent (single-domain) proteins and as domains within
      larger polypeptides. Here, we present a comprehensive structural classification
      of approximately 3000 small, disulfide-rich protein domains. We find that these
      domains can be arranged into 41 fold groups on the basis of structural
      similarity. Our fold groups, which describe broader structural relationships than
      existing groupings of these domains, bring together representatives with
      previously unacknowledged similarities; 18 of the 41 fold groups include domains
      from several SCOP folds. Within the fold groups, the domains are assembled into
      families of homologs. We define 98 families of disulfide-rich domains, some of
      which include newly detected homologs, particularly among knottin-like domains.
      On the basis of this classification, we have examined cases of convergent and
      divergent evolution of functions performed by disulfide-rich proteins. Disulfide
      bonding patterns in these domains are also evaluated. Reducible disulfide bonding
      patterns are much less frequent, while symmetric disulfide bonding patterns are
      more common than expected from random considerations. Examples of variations in
      disulfide bonding patterns found within families and fold groups are discussed.

PMID- 16618492
TI  - The folding pathway of spectrin R17 from experiment and simulation: using
      experimentally validated MD simulations to characterize States hinted at by
      experiment.
AB  - We present an experimental and computational analysis of the folding pathway of
      the 17th domain of chicken brain alpha-spectrin, R17. Wild-type R17 folds in a
      two-state manner and the chevron plot (plot of the logarithm of the observed rate
      constant against concentration of urea) shows essentially linear folding and
      unfolding arms. A number of mutant proteins, however, show a change in slope of
      the unfolding arm at high concentration of denaturant, hinting at complexity in
      the folding landscape. Through a combination of mutational studies and high
      temperature molecular dynamics simulations we show that the folding of R17 can be
      described by a model with two sequential transition states separated by an
      intermediate species. The rate limiting transition state for folding in water has
      been characterized both through experimental Phi-value analysis and by
      simulation. In contrast, a detailed analysis of the transition state predicted to
      dominate under highly denaturing conditions is only possible by simulation.

PMID- 16618493
TI  - Recombinant Thermus aquaticus RNA polymerase for structural studies.
AB  - Advances in the structural biology of bacterial transcription have come from
      studies of RNA polymerases (RNAPs) from the thermophilic eubacteria Thermus
      aquaticus (Taq) and Thermus thermophilus (Tth). These structural studies have
      been limited by the fact that only endogenous Taq or Tth RNAP, laboriously
      purified from large quantities of Taq or Tth cell paste and offering few options
      for genetic modification, is suitable for structural studies. Recombinant systems
      for the preparation of Taq RNAP by co-overexpression and assembly in the
      heterologous host, Escherichia coli, have been described, but these did not yield
      enzyme suitable for crystallographic studies. Here we describe recombinant
      systems for the preparation of Taq RNAP harboring full or partial deletions of
      the Taq beta' non-conserved domain (NCD), yielding enzyme suitable for
      crystallographic studies. This opens the way for structural studies of
      genetically manipulated enzymes, allowing the preparation of more crystallizable
      enzymes and facilitating detailed structure/function analysis. Characterization
      of the Taqbeta'NCD deletion mutants generated in this study showed that the
      beta'NCD is important for the efficient binding of the sigma subunit, confirming
      previous hypotheses. Finally, preliminary structural analysis (at 4.1Angstroms
      resolution) of one of the recombinant mutants revealed a previously unobserved
      conformation of the beta-flap, further defining the range of conformations
      accessible to this flexible structural element.

PMID- 16618494
TI  - Crystal structures of the lytic transglycosylase MltA from N.gonorrhoeae and
      E.coli: insights into interdomain movements and substrate binding.
AB  - MltA is a lytic transglycosylase of Gram-negative bacteria that cleaves the beta
      1,4 glycosidic linkages between N-acetylmuramic acid (MurNAc) and N
      acetylglucosamine (GlcNAc) in peptidoglycan. We have determined the crystal
      structures of MltA from Neisseria gonorrhoeae and Escherichia coli (NgMltA and
      EcMltA), which have only 21.5% sequence identity. Both proteins have two main
      domains separated by a deep groove. Domain 1 shows structural similarity with the
      so-called double-psi barrel family of proteins. Comparison of the two structures
      reveals substantial differences in the relative positions of domains 1 and 2 such
      that the active site groove in NgMltA is much wider and appears more able to
      accommodate peptidoglycan substrate than EcMltA, suggesting that domain closure
      occurs after substrate binding. Docking of a peptidoglycan molecule into the
      structure of NgMltA reveals a number of conserved residues that are likely
      involved in substrate binding, including a potential binding pocket for the
      peptidyl moieties. This structure supports the assignment of Asp405 as the acid
      catalyst responsible for cleavage of the glycosidic bond. In EcMltA, the
      equivalent residue is Asp328, which has been identified previously. The
      structures also suggest a catalytic role for Asp393 (Asp317 in EcMltA) in
      activating the C6 hydroxyl group during formation of the 1,6-anhydro linkage.
      Finally, in comparison to EcMltA, NgMltA contains a unique third domain that is
      an insertion within domain 2. The domain is beta in structure and may mediate
      protein-protein interactions that are specific to peptidoglycan metabolism in
      N.gonorrhoeae.

PMID- 16618495
TI  - Removal of phenol and substituted phenols by newly developed emulsion liquid
      membrane process.
AB  - Emulsion liquid membrane (ELM) stabilized by non-Newtonian conversion of the
      liquid membrane phase and dispersed in a Taylor-Couette flow was applied to treat
      model industrial wastewaters containing phenols and selected substituted phenols
      (hydroquinone, three chlorophenols and two nitrophenols) at relatively high
      concentrations. Under optimized operating conditions, all the compounds except
      hydroquinone were extracted with the maximum extraction efficiency of over 96%
      and the time to reach maximum extraction ranged from 2 to 30 min. For 2
      chlorophenol, 2,4-dichlorophenol, and 2-nitrophenol, maximum extraction
      efficiency of over 99% was reached in less than 2 min of contact time. Extraction
      of these compounds from the mixture was also highly efficient. Factors that
      affected the overall extraction efficiency such as acid-base speciation of the
      target compounds and the affinity between the target compounds and the membrane
      phase were determined. This study suggested that the newly developed ELM process
      might provide a promising alternative technology to treat industrial wastewaters
      containing high concentrations of phenolic compounds.

PMID- 16618496
TI  - Nitrate concentrations in river waters of the upper Thames and its tributaries.
AB  - The spatial and temporal patterns of in-stream nitrate concentrations for the
      upper Thames and selected tributaries are described in relation to point and
      diffuse sources for these rural catchments. The rivers associated with catchments
      dominated by permeable (Cretaceous Chalk) bedrock show a smaller range in nitrate
      concentrations than those associated with clay and mixed sedimentary bedrock of
      lower permeability. The differences reflect the contrasting nature of water
      storage within the catchments and the influence of point and diffuse sources of
      nitrate. Nitrate concentrations often increase in a gradual way as a function of
      flow for the rivers draining the permeable catchments, although there is usually
      a minor dip in nitrate concentrations at low to intermediate flow due to (1)
      within-river uptake of nitrate during the spring and the summer when biological
      activity is particularly high and (2) a seasonal fall in the water table and a
      change in preferential flow-pathway in the Chalk. There is also a decrease in the
      average nitrate concentration downstream for the Kennet where average
      concentrations decrease from around 35 to 25 mg NO(3) l(-1). For the lower
      permeability catchments, when point source inputs are not of major significance,
      nitrate concentrations in the rivers increase strongly with increasing flow and
      level off and in some cases then decline at higher flows. When point source
      inputs are important, the initial increase in nitrate concentrations do not
      always occur and there can even be an initial dilution, since the dilution of
      point sources of nitrate will be lowest under low-flow conditions. For the only
      two tributaries of the Thames which we have monitored for over 5 years (the Pang
      and the Kennet), nitrate concentrations have increased over time. For the main
      stem of the Thames, which was also monitored for over 5 years, there is no clear
      increase over time. As the Pang and the Kennet river water is mainly supplied
      from the Chalk, the increasing nitrate concentrations over time clearly reflect
      increasing nitrate concentrations within the groundwater. It primarily reflects
      long-term trends for agricultural fertilizer inputs and significant aquifer
      storage and long water residence times. The results are discussed in terms of
      hydrogeochemical processes and the Water Framework Directive and are compared
      with data from other eastern UK rivers. The importance of diffuse sources of
      nitrate contamination is highlighted. On a flow weighted basis, the average
      diffuse component of nitrate is around 95% for the Thames Basin rivers draining
      Chalk and for the corresponding rivers draining less permeable strata, there is a
      more significant but not major point source component (at least in terms of
      flux); the average diffuse component is 79% in this case. These data fit well
      with earlier assessments of agricultural sources to UK surface waters. Under
      baseflow conditions the diffuse sources remain dominant for the Chalk fed Thames
      Basin rivers, but point sources can be dominant for the low permeability cases.
      On a proportionate basis, the Thames Basin rivers are similar to the rural rivers
      of the Tweed and Humber Basins in terms of percentage diffuse components although
      the lower intensity agriculture occurring for the rivers monitored means that the
      average nitrate concentrations are lower for the rural rivers of central and
      northern England and the borders with Scotland: the Humber and Tweed.

PMID- 16618497
TI  - Serum selenium in adult Taiwanese.
AB  - The levels of serum selenium in 2755 individuals (1424 males, 1331 females) in
      Taiwan were determined by graphite furnace atomic absorption spectrometry. The
      average selenium concentration in serum was 110.9 microg/l with a standard
      deviation of 21.5 microg/l, ranging from 40.5 to 186 microg/l. The observation
      was higher than those recently reported in European regions but comparable to
      those observed in the USA or seleniferous regions. Serum selenium level did not
      vary with the gender, educational levels of the subjects and smoking habits.
      Serum selenium content seemed drop considerably if one is older than 39 years
      old. Age and alcohol consumption had statistically significant difference with
      serum selenium concentration.

PMID- 16618498
TI  - From dust to dose: Effects of forest disturbance on increased inhalation
      exposure.
AB  - Ecosystem disturbances that remove vegetation and disturb surface soils are major
      causes of excessive soil erosion and can result in accelerated transport of soils
      contaminated with hazardous materials. Accelerated wind erosion in disturbed
      lands that are contaminated is of particular concern because of potential
      increased inhalation exposure, yet measurements regarding these relationships are
      lacking. The importance of this was highlighted when, in May of 2000, the Cerro
      Grande fire burned over roughly 30% of Los Alamos National Laboratory (LANL),
      mostly in ponderosa pine (Pinus ponderosa) forest, and through areas with soils
      containing contaminants, particularly excess depleted and natural uranium.
      Additionally, post-fire thinning was performed in burned and unburned forests on
      about 25% of LANL land. The first goal of this study was to assess the potential
      for increased inhalation dose from uranium contaminated soils via wind-driven
      resuspension of soil following the Cerro Grande Fire and subsequent forest
      thinning. This was done through analysis of post-disturbance measurements of
      uranium air concentrations and their relationships with wind velocity and
      seasonal vegetation cover. We found a 14% average increase in uranium air
      concentrations at LANL perimeter locations after the fire, and the greatest air
      concentrations occurred during the months of April-June when wind velocities are
      highest, no snow cover, and low vegetation cover. The second goal was to develop
      a methodology to assess the relative contribution of each disturbance type
      towards increasing public and worker exposure to these resuspended soils.
      Measurements of wind-driven dust flux in severely burned, moderately burned,
      thinned, and unburned/unthinned forest areas were used to assess horizontal dust
      flux (HDF) in these areas. Using empirically derived relationships between
      measurements of HDF and respirible dust, coupled with onsite uranium soil
      concentrations, we estimate relative increases in inhalation doses for workers
      ranging from 15% to 38%. Despite the potential for increased doses resulting from
      these forest disturbances, the estimated annual dose rate for the public was <1
      microSv yr(-1), which is far below the dose limits for public exposures, and the
      upper-bound dose rate for a LANL worker was estimated to be 140 microSv yr(-1),
      far below the 5 x 10(4) microSv yr(-1) occupational dose limit. These results
      show the importance of ecosystem disturbance in increasing mobility of soil-bound
      contaminants, which can ultimately increase exposure. However, it is important to
      investigate the magnitude of the increases when deciding appropriate strategies
      for management and long-term stewardship of contaminated lands.

PMID- 16618499
TI  - Vitamin D in foods and as supplements.
AB  - Numerous studies have shown that the vitamin D status is far from optimal in many
      countries all over the world. The main reason for this is lack of sunshine. Only
      a limited number of foods naturally contain vitamin D. Good sources of vitamin
      D(3) are fish (not only fatty fish), egg yolk, and offal such as liver. Some
      foods such as milk are fortified with vitamin D in some countries. Dietary
      vitamin D intake is low in many countries, especially as the dietary sources are
      limited. The use of supplements is important and seems to be high in some
      countries. Current dietary intake recommendations are too low to preserve/reach
      optimal S-25-OHD concentrations, when UVB radiation is not available. We suggest
      that the recommendations should be increased to at least 10 microg per day in all
      age groups when solar UVB is scarce. The elderly may need a daily vitamin D
      intake of 25 microg. If dietary intake of vitamin D is to be increased, food
      habits will have to change. From a public health point of view it is better to
      increase the potential sources of vitamin D by fortifying specific products that
      are consumed commonly in a whole population, or if necessary by especially
      vulnerable groups. Supplement use is probably the right alternative for
      vulnerable groups such as infants and inactive elderly in whom this is more
      easily implemented.

PMID- 16618500
TI  - Development of a soft tissue seal around bone-anchored transcutaneous amputation
      prostheses.
AB  - Conventional amputation prosthetics are problematic because they rely on the
      stump-socket interface for attachment. Intraosseous transcutaneous amputation
      prostheses (ITAP) could solve these problems; however they rely on the integrity
      of the soft tissue-implant interface as a barrier to exogenous agents, and in the
      prevention of downgrowth and marsupilisation. We have used an in vivo animal
      model to study the soft tissue interfaces around bone-anchored transcutaneous
      implants. We hypothesise that by facilitating and increasing the area of dermal
      attachment to the implant epithelial down-growth will be reduced. A flange with a
      series of 24, 0.7 mm holes positioned immediately below the epithelium was used
      to increase dermal attachment. This significantly reduced downgrowth and
      optimised the integrity of the collagenous tissue-implant interface at the dermal
      level. We postulate that the flange reduces relative interfacial movement at the
      epithelium-implant interface by providing increased surface area for dermal
      tissue attachment. A tight seal at the dermal tissue level reduces the degree of
      downgrowth around ITAP, eliminating marsupilisation as a potential failure
      modality. Surface topography and coatings did not affect the degree of downgrowth
      or dermal attachment to straight or flanged implants. A significant negative
      correlation was observed between downgrowth and both epithelial and dermal
      attachment. This study shows that a soft tissue-implant interface capable of
      preventing downgrowth and marsupilisation can develop around a bone-anchored
      transcutaneous implant, given the incorporation of a porous flange positioned in
      the dermal tissues immediately below the epithelium. This will benefit
      applications where bone-anchored transcutaneous implants are used.

PMID- 16618501
TI  - The influence of processes for the purification of human bone allografts on the
      matrix surface and cytocompatibility.
AB  - Different industrial processes exist to purify allogenic bone, providing safe and
      cleaned blocks for bone allografting. However, they often make use of chemical
      reagents that can be aggressive for the bone matrix. Bone samples were processed
      with several soaking techniques used in industry: NaHCO3, H2O2, NaOH and
      H2O2+NaOH combined; the consequences on the bone matrix and cytocompoatibility
      were evaluated on femoral heads from osteoarthritic patients. Alterations of
      matrix were searched by histochemistry, atomic force microscopy (AFM), scanning
      electron microscopy (SEM) and transmission electron microscopy (TEM).
      Cytocompatibility was evaluated by coculturing human osteoblast-like cells (SaOS
      2) on bone slices. Collagen fibers were dramatically altered at the surface of
      bone treated with H2O2, NaOH (and their association), but not with NaHCO3. A
      marked reduction in the number of hydroxyapatite crystals was observed on the
      trabecular surfaces by TEM and morphological changes were evidenced in SEM and
      AFM. Argyrophilic proteins of the bone matrix were removed by H2O2 and NaOH (and
      their association), but not by NaHCO3. As a consequence, attachment, spreading,
      proliferation and alkaline phosphatase activity of SaOS-2 were reduced by H2O2
      and NaOH treatments. Strong oxidizing reagents altered matrix integrity by
      modifying collagenous and non-collagenous proteins. Whether these changes have
      clinical consequences on the bone bonding and osseointegration in human
      necessitate further investigations.

PMID- 16618502
TI  - Early bone apposition in vivo on plasma-sprayed and electrochemically deposited
      hydroxyapatite coatings on titanium alloy.
AB  - Three different implants, bare Ti-6Al-4V alloy, Ti-6Al-4V alloy coated with
      plasma-sprayed hydroxyapatite (PSHA), and Ti-6Al-4V alloy coated with
      electrochemically deposited hydroxyapatite (EDHA), were implanted into canine
      trabecular bone for 6 h, 7, and 14 days, respectively. Environmental scanning
      electron microscopy study showed that PSHA coatings had higher bone apposition
      ratios than those exhibited by bare Ti-6Al-4V and EDHA coatings after 7 days;
      however, at 14 days after implantation, EDHA and PSHA coatings exhibited similar
      bone apposition ratios, much higher than that for bare Ti-6Al-4V. The
      ultrastructure of the bone/implant interface observed by transmission electron
      microscope showed that the earliest mineralization (6 h-7 days) was in the form
      of nano-ribbon cluster mineral deposits with a Ca/P atomic ratio lower than that
      of hydroxyapatite. Later-stage mineralization (7-14 days) resulted in bone-like
      tissue with the characteristic templating of self-assembled collagen fibrils by
      HA platelets. Though adhesion of EDHA coatings to Ti-6Al-4V substrate proved
      problematical and clearly needs to be addressed through appropriate manipulation
      of electrodepositon parameters, the finely textured microstructure of EDHA
      coatings appears to provide significant advantage for the integration of
      mineralized bone tissue into the coatings.

PMID- 16618503
TI  - Dynamic simulation method to characterise oxygen transport in hydrogel membranes.

PMID- 16618504
TI  - In vivo evaluation of an oral delivery system for P-gp substrates based on
      thiolated chitosan.
AB  - Recently, thiolated polymers, so called thiomers, have been reported to modulate
      drug absorption by inhibition of intestinal P-glycoprotein (P-gp). The aim of the
      present study was to provide a proof-of-principle for a delivery system based on
      thiolated chitosan in vivo in rats, using rhodamine-123 (Rho-123) as
      representative P-gp substrate. In vitro, the permeation enhancing effect of
      unmodified chitosan, chitosan-4 thiobutylamidine (Ch-TBA) and the combination of
      Ch-TBA with reduced glutathione (GSH) was evaluated by using freshly excised rat
      intestinal mucosa mounted in Ussing-type chambers. In comparison to buffer only,
      Rho-123 transport in presence of 0.5% (w/v) chitosan, 0.5% (w/v) Ch-TBA and the
      combination of 0.5% (w/v) Ch-TBA/0.5% (w/v) GSH, was 1.8-fold, 2.6-fold, 3.8-fold
      improved, respectively. Furthermore, enteric-coated tablets based on unmodified
      chitosan or Ch-TBA/GSH, were investigated in vivo. In rats, the Ch-TBA/GSH
      tablets increased the area under the plasma concentration time curve (AUC0-12) of
      Rho-123 by 217% in comparison to buffer control and by 58% in comparison to
      unmodified chitosan. This in vivo study showed that a delivery system based on
      thiolated chitosan significantly increased the oral bioavailability of P-gp
      substrate Rho-123.

PMID- 16618505
TI  - Heavy metal dispersion, persistance, and bioccumulation around an ancient copper
      mine situated in Anglesey, UK.
AB  - The vicinity of an ancient abandoned copper mine located on the Isle of Anglesey
      was assessed for the dispersion of copper, zinc, lead, and cadmium into the
      surrounding environment. Extraction of soil, lichens, cattle feces, and Calluna
      vulgaris L. (ling) tissue, using aqua regia, was carried out and together with
      water samples, these were analyzed using flame atomic absorption spectroscopy.
      Atmospheric dispersion and dilution was plotted from the workings to the coast
      and the resultant dilution ascertained. Evidence of bioaccumulation by plants and
      animals is presented and partitioning within plants highlighted. The results
      suggest that atmospheric dispersion has ceased but residual metal concentrations
      in the soil remain persistent and could present health hazards to animals and
      humans in the past and in the future.

PMID- 16618506
TI  - QSPRs on photodegradation half-lives of atmospheric chlorinated polycyclic
      aromatic hydrocarbons associated with particulates.
AB  - A quantitative structure-property relationship (QSPR) model which could predict
      photodegradation half-lives (t(1/2)) of chlorinated polycyclic aromatic
      hydrocarbons (ClPAHs) associated with particulates in the atmosphere was
      developed by applying quantum chemical parameters computed with quantum chemical
      PM3 algorithm and using a partial least squares (PLS) algorithm. The cross
      validated Q(2)(cum) value for the optimal QSPR model is 0.960, indicating a good
      predictive capability for logt(1/2) values of ClPAHs. The QSPR results show that
      the main factors affecting logt(1/2) values of ClPAHs are the energy of the
      second highest occupied molecular orbital (E(LUMO-1)), the energy of the second
      highest occupied molecular orbital (E(HOMO+1)), average molecular polarizability
      (alpha), the most positive net atomic charges on a hydrogen atom (Q(H)(+)),
      E(LUMO)+E(HOMO), E(LUMO)-E(HOMO), and (E(LUMO)-E(HOMO))(2). ClPAHs with high
      E(LUMO-1), E(HOMO+1), E(LUMO)-E(HOMO,) and (E(LUMO)-E(HOMO))(2) values tend to
      photolyze slowly in the atmosphere. In contrast, increasing E(LUMO)+E(HOMO),
      alpha, and Q(H)(+) values leads to the increase of photodegradation rates.

PMID- 16618507
TI  - Shortened lifespan of nematode Caenorhabditis elegans after prolonged exposure to
      heavy metals and detergents.
AB  - The acute toxicities of heavy metals and detergents have been well examined with
      respect to several endpoints, such as mortality, for application to toxicity
      tests for environmental assessments. However, chronic influences of these agents
      on multicellular organisms still need to be determined. Here we studied long-term
      effects on the lifespan of a free-living nematode, Caenorhabditis elegans,
      resulting from prolonged exposure to heavy metals or detergents, as well as short
      term inhibitory effects on reproduction and growth. These agents inhibited growth
      of hatched larvae and reproductive capacity in a concentration-dependent manner.
      They also effectively shortened the lifespan of the adult nematode over the same
      concentration range. Since toxic effects on both growth and lifespan were
      observed over similar concentration ranges, where acute toxicities in various
      endpoints are detected, the shortening of the lifespan can be used as a new
      endpoint for the assessment of various ecotoxic agents.

PMID- 16618508
TI  - Evaluation of a commercial kit for measuring vitellogenin in the fathead minnow
      (Pimephales promelas).
AB  - Vitellogenin (vtg) concentrations in oviparous animals such as fish represent an
      integrated indicator of the status of the reproductive endocrine system. As such,
      vtg is a common measurement endpoint in tests designed to detect certain classes
      of endocrine-disrupting chemicals (EDCs). The most common approach to measuring
      vtg is via enzyme-linked immunosorbent assays (ELISAs). However, because labs
      testing EDCs in fish often use slightly different ELISAs (e.g., in terms of
      antibodies, binding antigens, standards), results among studies are not always
      comparable. One approach to obviating this would be for researchers to use
      standardized ELISA kits from a common source(s). The fathead minnow (Pimephales
      promelas) is a small fish model commonly used for EDC testing. The purpose of
      this study was to evaluate a recently developed commercial ELISA kit for
      measuring vtg in the fathead minnow. The commercial ELISA, based on a monoclonal
      antibody to fathead minnow vtg, was compared to an ELISA that utilizes a fathead
      minnow polyclonal antibody, which has been used extensively in our lab and others
      for several years. Plasma samples for this comparison came from three studies in
      which fathead minnows had been exposed to different model EDCs, including an
      androgen (17beta-trenbolone), an anti-androgen (flutamide), and two CYP19
      (aromatase) inhibitors (prochloraz, fadrozole). Results obtained using the two
      different ELISA methods were consistently similar.

PMID- 16618509
TI  - The stress-induced hyperthermia paradigm as a physiological animal model for
      anxiety: a review of pharmacological and genetic studies in the mouse.
AB  - This paper reviews the function, brain mechanisms and pharmacology of stress
      induced hyperthermia (SIH) in a broad context. Hyperthermia itself is induced by
      all stressful stimuli and can be found across numerous species, including humans.
      As a model for anxiety, the process of insertion of a rectal probe increases
      temperature ranging from about 0.5-1.5 degrees C in 10-15min is called SIH. This
      temperature increase can be blocked by anxiolytic drugs. The methodological as
      well as pharmacological aspects of the group- (G-SIH) and singly housed (SIH)
      version of the paradigm are described in detail. Also, an overview is presented
      about studies using the SIH procedure in genetically modified mice together with
      the potential interference with immunological induction of a febrile response.
      The paper also presents data that highlight some of the limitations of the SIH
      procedure for use of drugs like nicotine, which contain particular
      characteristics such as short in vivo half-life, and/or disturbance of
      thermoregulation. The advantages and disadvantages of the SIH procedure as a
      physiological model of anxiety are discussed.

PMID- 16618510
TI  - A rare cause of infective endocarditis; Lactococcus garvieae.

PMID- 16618511
TI  - Monte Carlo dosimetric evaluation of high energy vs low energy photon beams in
      low density tissues.
AB  - BACKGROUND AND PURPOSE: Low megavoltage photon beams are often the treatment
      choice in radiotherapy when low density heterogeneities are involved, because
      higher energies show some undesirable dosimetric effects. This work is aimed at
      investigating the effects of different energy selection for low density tissues.
      PATIENTS AND METHODS: BEAMnrc was used to simulate simple treatment set-ups in a
      simple and a CT reconstructed lung phantom and an air-channel phantom. The dose
      distribution of 6, 15 and 20 MV photon beams was studied using single, AP/PA and
      three-field arrangements. RESULTS: Our results showed no significant changes in
      the penumbra width in lung when a pair of opposed fields were used. The
      underdosage at the anterior/posterior tumor edge caused by the dose build-up at
      the lung-tumor interface reached 7% for a 5 x 5 cm AP/PA set-up. Shrinkage of the
      90% isodose volume was noticed for the same set-up, which could be rectified by
      adding a lateral field. For the CT reconstructed phantom, the AP/PA set-up
      offered better tumor coverage when lower energies were used but for the three
      field set-up, higher energies resulted to better sparing of the lung tissue. For
      the air-channel set-up, adding an opposed field reduced the penumbra width. Using
      higher energies resulted in a 7% cold spot around the air-tissue interface for a
      5 x 5 cm field. CONCLUSIONS: The choice of energy for treatment in the low
      density areas is not a straightforward decision but depends on a number of
      parameters such as the beam set-up and the dosimetric criteria. Updated
      calculation algorithms should be used in order to be confident for the choice of
      energy of treatment.

PMID- 16618512
TI  - The expanding role of the bile acid receptor FXR in the small intestine.

PMID- 16618513
TI  - Macrophage activating syndrome is associated with lobular hepatitis and severe
      bile duct injury with cholestasis.
AB  - Macrophage activating syndrome (MAS) is a rare hematological disorder associated
      with uncontrolled systemic T-cell activation. Persistent fever, fatigue and
      hepatosplenomegaly are frequent clinical manifestations, whereas
      hyperferritinemia, elevated serum lactate dehydrogenase levels and cytopenia are
      key criteria for the diagnosis of MAS. The nature of liver pathology in MAS has
      been partially elucidated but destructive biliary lesions have been rarely
      described. This report illustrates four cases of MAS developing marked
      cholestasis, leading to one case of biliary cirrhosis necessitating liver
      transplantation. Histologically, liver involvement was characterized in all cases
      by acute lobular hepatitis, marked hepatocyte apoptosis and small bile duct
      injury similar to the vanishing bile duct syndrome. Immuno-histological studies
      showed that the inflammatory changes and bile duct lesions were dominated by the
      presence of activated macrophages and T-cells, in particular CD8+ lymphocytes,
      and in part NK-cells. These findings suggest that in MAS, various T-cell triggers
      such as infection, autoimmune disease and malignancy might result in the release
      of cytokines, which in turn activate macrophages to trigger a systemic acute
      phase response and local tissue damage. This communication suggests that a
      macrophage, T- and NK-cell network is operational in the pathogenesis of the
      cholangiocyte, hepatocyte and sinus endothelial cell damage in MAS.

PMID- 16618514
TI  - Prediction model of hepatocarcinogenesis for patients with hepatitis C virus
      related cirrhosis. Validation with internal and external cohorts.
AB  - BACKGROUND/AIMS: To estimate hepatocarcinogenesis rates in patients with
      hepatitis C virus (HCV)-related cirrhosis, an accurate prediction table was
      created. METHODS: A total of 183 patients between 1974 and 1990 were assessed for
      carcinogenesis rate and risk factors. Predicted carcinogenesis rates were
      validated using a cohort from the same hospital between 1991 and 2003 (n=302) and
      an external cohort from Tokyo National Hospital between 1975 and 2002 (n=205).
      RESULTS: The carcinogenesis rates in the primary cohort were 28.9% at the 5th
      year and 54.0% at the 10th year. A proportional hazard model identified alpha
      fetoprotein (>or=20 ng/ml, hazard ratio 2.30, 95% confidence interval 1.55-3.42),
      age (>or=55 years, 2.02, 95% CI 1.32-3.08), gender (male, 1.58, 95% CI 1.05
      2.38), and platelet count (<100,000 counts/mm3, 1.54, 95% CI 1.04-2.28) as
      independently associated with carcinogenesis. When carcinogenesis rates were
      simulated in 16 conditions according to four binary variables, the 5th- and 10th
      year rates varied from 9 to 64%, and 21-93%, respectively. Actual carcinogenesis
      rates in the internal and external validation cohorts were similar to those of
      the simulated curves. CONCLUSIONS: Simulated carcinogenesis rates were applicable
      to patients with HCV-related cirrhosis. Since, hepatocarcinogenesis rates
      markedly varied among patients depending on background features, we should
      consider stratifying them for cancer screening and cancer prevention programs.

PMID- 16618515
TI  - From viral pathobiology to the treatment of hepatitis B virus infection EASL
      Monothematic Conference (Istanbul, Turkey, October 6-8, 2005).

PMID- 16618516
TI  - 'Endocrine NAFLD' a hormonocentric perspective of nonalcoholic fatty liver
      disease pathogenesis.

PMID- 16618517
TI  - Systemic inflammation in nonalcoholic fatty liver disease is characterized by
      elevated levels of CCL2.
AB  - BACKGROUND/AIMS: To elucidate the role of systemic inflammation in nonalcoholic
      fatty liver disease (NAFLD). METHODS: Serum samples in 47 patients with
      histologically verified NAFLD (22 with simple steatosis and 25 with nonalcoholic
      steatohepatitis [NASH]), and in 30 age-, sex- and ethnicity-matched healthy
      controls, were assessed for (i) general markers of inflammation (C-reactive
      protein [CRP], tumor necrosis factor [TNF]-alpha, and interleukin [IL]-6), (ii)
      chemokines (CC-chemokine ligand [CCL] 2/monocyte chemoattractant protein [MCP]-1,
      CCL19 and CCL21), (iii) adipocytokines related to insulin resistance and
      inflammation (adiponectin and leptin) and (iv) a marker of oxidative stress (8
      isoprostane-F2alpha). RESULTS: Serum levels of several inflammatory cytokines
      were increased in NAFLD as compared to controls, and IL-6 (P=0.017), CCL2/MCP-1
      (P=0.008) and CCL19 (P=0.001), but not CRP (P=0.199), remained elevated also
      after correction for sex, body mass index (BMI) and age. Comparing NASH with
      simple steatosis, levels of TNF-alpha (P=0.024) and CCL2/MCP-1 (P=0.012) were
      elevated and adiponectin (in women) (P=0.001) were decreased also after
      adjustment for sex, BMI and presence of the metabolic syndrome. CONCLUSIONS: Our
      results indicate that patients with NAFLD are characterized by a low-grade
      systemic inflammation. The high CCL2/MCP-1 levels in NASH might be of importance
      for the conversion from simple steatosis to NASH.

PMID- 16618518
TI  - Impact of human immunodeficiency virus infection on the prevalence and severity
      of steatosis in patients with chronic hepatitis C virus infection.
AB  - BACKGROUND/AIMS: Although steatosis is strongly associated with hepatitis C virus
      (HCV) infection, little is known about this finding in patients coinfected with
      human immunodeficiency virus (HIV) and HCV. The aims of the present study were to
      determine the prevalence and severity of steatosis in HIV/HCV coinfected
      patients. METHODS: Consecutive patients undergoing liver biopsy were
      prospectively identified and were interviewed to obtain detailed demographic and
      clinical data. Steatosis was scored according to the percentage of hepatocytes
      involved: 0 (none), 1 (<33%), 2 (33-66%), or 3 (>66%); fibrosis was scored on a
      scale from 0 to 4. RESULTS: A total of 708 patients were enrolled, including 154
      with HIV/HCV coinfection and 554 with HCV monoinfection. Steatosis of any grade
      (72.1 vs. 52.0%, P<0.001), grade 2/3 steatosis (48.1 vs. 20.2%, P<0.001), and
      stage 3/4 fibrosis (43.5 vs. 30.0%, P=0.002) were significantly more common in
      coinfected patients. Compared to HCV monoinfected subjects, HIV/HCV coinfection
      was associated with a significantly increased odds of steatosis of any grade
      (OR=3.21; 95% CI, 1.84-5.60) and grade 2/3 steatosis (OR=5.63; 95% CI, 3.05
      10.36) after adjusting for potential confounding variables. Among coinfected
      patients, the fibrosis progression rate increased in a linear fashion with the
      grade of steatosis. CONCLUSIONS: Steatosis is more common and more severe in
      HIV/HCV coinfected patients than in those with HCV monoinfection.

PMID- 16618519
TI  - Cloning and molecular characterization of a functional flavonoid 3'-hydroxylase
      gene from Brassica napus.
AB  - A flavonoid 3'-hydroxylase (F3'H) gene, denoted BnF3'H-1, was cloned from oilseed
      rape (Brassica napus). The gene of 3038 base pairs (bp) contains 3 introns. The
      complementary DNA (cDNA) consists of 1820bp and has an open reading frame of
      1536bp encoding a polypeptide of 511 amino acids with a molecular weight of
      56.62kDa and an isoelectric point of 7.08. BnF3'H-1 shows high homology to known
      F3'H genes, especially F3'H from Arabidopsis thaliana. Untranslated regions
      (UTRs) may play important roles in regulating the expression of BnF3'H-1. Besides
      containing a Kozak sequence, the first 77-bp region is C-rich but G-poor, and the
      26-bp 5'-UTR contains 3 sites of ACCACT-like sequences. Alternative
      polyadenylation in the 3'-UTR is adopted by this gene to generate heterogeneous
      transcripts. Conserved domain search and motif characterization identified BnF3'H
      1 as a cytochrome P450. All F3'H-featured motifs, VVVAAS, GGEK and VDVKG, are
      unchanged in BnF3'H-1. The N-terminal signal peptide/anchor and 3 transmembrane
      helices were predicted in BnF3'H-1, and its subcellular localization is most
      probably at the endoplasmic reticulum. Since 16 phosphorylation sites could be
      predicted, phosphorylation may be a necessary post-translational modification of
      BnF3'H-1. The secondary structure is dominated by alpha-helices and random coils.
      Most helices are located in the middle region, while extended strands mainly
      intersperse in terminal regions. DNA gel blot analysis indicated that 2 different
      F3'H genes might exist in B. napus. Semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) and RNA gel blot analysis showed that flowers
      have the highest F3'H expression, followed by pericarp and seed, and lower levels
      in some other organs. This species-featured expression pattern is in obedience to
      multiple functional roles that F3'H gene(s) play(s) in various organs of B.
      napus. The BnF3'H-1 coding region was expressed in Escherichia coli, and enzyme
      activity of the His-tagged protein was demonstrated by monitoring the conversion
      of the substrate naringenin using high-performance liquid chromatography (HPLC),
      suggesting that BnF3'H-1 is catalytically functional. RT-PCR analysis suggests
      that transcription level of the F3'H gene(s) is not the reason for the different
      seed colorations found in near-isogenic lines (black-seeded L1 and yellow-seeded
      L2) of B. napus.

PMID- 16618520
TI  - Cloning of two individual cDNAS encoding 9-cis-epoxycarotenoid dioxygenase from
      Gentiana lutea, their tissue-specific expression and physiological effect in
      transgenic tobacco.
AB  - Two 9-cis-epoxycarotenoid dioxygenase (NCED) cDNAs have been cloned from a petal
      library of Gentiana lutea. Both cDNAs carry a putative transit sequence for
      chloroplast import and differ mainly in their length and the 5'-flanking regions.
      GlNCED1 was evolutionary closely related to Arabidopsis thaliana NCED6 whereas
      GlNCED2 showed highest homology to tomato NCED1 and A. thaliana NCED3. The
      amounts of GlNCED2 transcript were below Northern detection in G. lutea. In
      contrast, GlNCED1 was specifically expressed at higher levels in developing
      flowers when petals start appearing. By genetic engineering of tobacco with
      coding regions of either gene under a constitutive promoter, their function was
      further analyzed. Although mRNA of both genes was detectable in the corresponding
      transgenic plants, a physiological effect was only found for GlNCED1 but not for
      GlNCED2. In germination experiments of GlNCED1 transgenic lines, delayed radicle
      formation and cotyledon appearance were observed. However, the transformants
      exhibited no improved tolerance against desiccation stress. In contrast to other
      plants with over-expressed NCEDs, prolonged delay of seed germination is the only
      abscisic-acid-related phenotypic effect in the GlNCED1 transgenic lines.

PMID- 16618521
TI  - Modification of chemical properties of cell walls by silicon and its role in
      regulation of the cell wall extensibility in oat leaves.
AB  - Effects of silicon on the mechanical and chemical properties of cell walls in the
      second leaf of oat (Avena sativa L.) seedlings were investigated. The cell wall
      extensibility in the basal region of the second leaf was considerably higher than
      that in the middle and subapical regions. Externally applied silicon increased
      the cell wall extensibility in the basal region, but it did not affect the
      extensibility in the middle and subapical regions. The amounts of cell wall
      polysaccharides and phenolic compounds, such as diferulic acid (DFA) and ferulic
      acid (FA), per unit length were lower in the basal region than in the middle and
      subapical regions of the leaf, and silicon altered these amounts in the basal
      region. In this region, silicon decreased the amounts of matrix polymers and
      cellulose per unit length and of DFA and FA, both per unit length and unit matrix
      polymer content. Silicon treatment also lowered the activity of phenylalanine
      ammonia-lyase (PAL, EC 4.3.1.5) in the basal region. In contrast, the amount of
      silicon in cell walls increased in response to silicon treatment in three
      regions. These results suggest that in the basal region, silicon reduces the net
      wall mass and the formation of phenolic acid-mediated cross-linkages between wall
      polysaccharides. Such modifications of wall architecture may be responsible for
      the silicon-induced increase in the cell wall extensibility in oat leaves.

PMID- 16618522
TI  - Flexible and reversible responses to different irradiance levels during
      photosynthetic acclimation of Cypripedium guttatum.
AB  - Cypripedium guttatum can be found both in open and shady habitats. Photosynthetic
      acclimation of C. guttatum to different light availabilities was detected using
      measurements of chlorophyll fluorescence, photosynthesis and leaf traits. When
      growing under low light conditions, C. guttatum exhibited a greater efficiency in
      photochemical utilization of absorbed light energy, and a lower ability for non
      photochemical dissipation of excess light energy, as compared to the plants
      growing under high light conditions. Under intermediate light conditions, C.
      guttatum exhibited higher photosynthetic capacity (A(max)) than those under both
      low light or high light conditions. The differences in A(max) among three light
      environments was linked to the differences in biochemical efficiency, leaf N
      content (LNC) and leaf dry mass per unit area (LMA), but not to the differences
      of chlorophyll content. However, there were no significant differences in the
      light compensation points (LCP) and light saturation points (LSP) for
      photosynthesis for the plants growing under the three light conditions. These
      results indicate that the photosynthetic capacity of C. guttatum leaves allows
      for flexible and reversible responses to different irradiance levels.
      Photosynthetic acclimation in C. guttatum was affected by biochemical changes,
      the changes in LMA and ratio of Chl a/b. Successful acclimation of C. guttatum to
      a broad range of light levels likely allows for its wide geographical
      distribution. A level of about 45% sunlight appears to be optimal for
      photosynthesis.

PMID- 16618523
TI  - Two-staged reconstruction of the flexor pollicis longus tendon.
AB  - The purpose of this study was to evaluate the results of two-stage reconstruction
      of the flexor pollicis longus (FPL) tendon. Sixteen patients who underwent
      reconstructive surgery of the FPL tendon were assessed retrospectively. Eight
      weeks after implantation of a silastic spacer, a tendon graft was used for
      reconstruction (thirteen palmaris longus tendons, two plantaris tendons, one half
      of the flexor carpi radialis tendon). Power grip, active range of motion, passive
      range of motion, the Buck-Gramcko assessment, the ASSH assessment and the DASH
      score were used to evaluate the results. Adequate function in 75% of the cases
      and a median of 11 on the DASH score was achieved. The results showed that two
      stage reconstruction of the FPL tendon can produce satisfactory results, even if
      primary repair is the ideal.

PMID- 16618524
TI  - Avascular necrosis of the pisiform.
AB  - Avascular necrosis of the pisiform bone is a very rare condition. This paper
      reports a case and discusses this pathology and its diagnosis.

PMID- 16618525
TI  - Unusual arterial anatomy in a case of index finger pollicization.

PMID- 16618526
TI  - Extensor pollicis longus tendon rupture due to scaphoid non-u.

PMID- 16618527
TI  - Water quality assessment using remote sensing techniques: Medrano Creek,
      Argentina.
AB  - Two spectral bands of the visible spectrum [0.45-0.52 microm (Blue), 0.52-0.60
      microm (Green)] of satellite images obtained by LANDSAT 7 ETM+ have been used in
      this study to follow the contaminated waters of Medrano Creek when it flows into
      Rio de la Plata River. The former is one of the five fresh watercourses going
      through the Metropolitan Area of Buenos Aires, Argentina, where 13 million people
      live. Previous studies have shown that the water quality of Rio de la Plata at
      the outlet of Medrano Creek has decreased more than 50% as a source of water for
      human consumption. The non-treated effluents of the textile industry probably
      affect the water quality. We have developed a model that predicts the water
      quality index (WQI) of surface waters in the study area and uses linear
      regression analysis. The model has been validated using a data set of 12
      physicochemical parameters obtained during the last 3 years. The potentiality of
      using satellite images was confirmed by the results: (a) to trace the organic
      contamination (associated with dyes) in freshwater systems and (b) as tools for
      decision making in the management of water resources.

PMID- 16618528
TI  - Efficiency analysis for organic agricultural producers: the role of soil
      improving inputs.
AB  - Greater emphasis is being placed on indicators of agri-environmental efficiency
      of organic production systems. Linking environmental measures with profitability
      measures based on net income is the only way to develop such indicators. A
      stochastic production frontier model that explicitly incorporates farm decisions
      about acquiring and managing organic soil-improving inputs is used to measure
      efficiency. The results confirm that on-farm self-sufficiency in soil-improving
      inputs is positively related to farm-level efficiency.

PMID- 16618529
TI  - Color removal from dye-containing wastewater by magnesium chloride.
AB  - Color removal by MgCl(2) when treating synthetic waste containing pure dyes was
      studied. The color removal efficiency of MgCl(2)/Ca(OH)(2) was compared with that
      of Al(2)(SO(4))(3), polyaluminum chloride (PAC) and FeSO(4)/Ca(OH)(2). The
      mechanism of color removal by MgCl(2) was also investigated. The experimental
      results show that the color removal efficiency of MgCl(2) is related to the type
      of dye and depends on the pH of the waste and the dosage of the coagulants used.
      Treatment of waste containing reactive dye or dispersed dye with MgCl(2) yielded
      an optimum color removal ratio when the pH of the solution was equal to or above
      12.0. For both the reactive and dispersed dye waste, MgCl(2)/Ca(OH)(2) was shown
      to be superior to MgCl(2)/NaOH, Al(2)(SO(4))(3), PAC and FeSO(4)/Ca(OH)(2) for
      color removal. A magnesium hydroxide precipitate formed at pH values greater than
      12.0, which provided a large adsorptive surface area and a positive electrostatic
      surface charge, enabling it to remove the dyes through charge neutralization and
      an adsorptive coagulating mechanism. So, the MgCl(2)/Ca(OH)(2) system is a viable
      alternative to some of the more conventional forms of chemical treatment,
      especially for treating actual textile waste with high natural pH.

PMID- 16618530
TI  - A graphical screening method for assessing stream water quality using specific
      conductivity and alkalinity data.
AB  - In areas of varying geology, it is difficult to infer water quality from specific
      conductance or electrical conductivity (EC) data without an understanding of the
      expected range of EC values based on local bedrock composition. This paper
      describes a user-friendly graphical screening method that addresses this issue by
      plotting the EC against concurrent alkalinity data, which correlates well with
      the presence of carbonate bedrock under natural conditions, and thus serves as an
      index of bedrock type. The upper limit of EC vs. alkalinity expected in a stream
      is determined using regional groundwater quality data, based on the assumption
      that stream chemistry reflects groundwater under baseflow conditions. Stream
      samples with EC/alkalinity values that consistently plot above this limit are
      considered impacted by anthropogenic sources. The effect of dilution and runoff
      on the EC vs. alkalinity plot of stream samples is considered using a simple
      baseflow/storm runoff-mixing model. The graphical method's utility as a screening
      tool is demonstrated by application to stream chemistry data from watersheds of
      southeastern Pennsylvania and northwestern New Jersey in several distinct
      geologic settings; however the method is general and widely applicable to
      watersheds in humid temperate regions. Its use is intended for watershed stewards
      of both professional and nonprofessional qualification.

PMID- 16618531
TI  - Comparative analysis of base correlations in 5' untranslated regions of various
      species.
AB  - Translational initiation signals, such as Shine-Dalgarno (SD) sequences in
      bacteria and Kozak consensus sequences in vertebrates, direct ribosomes to
      initiate protein synthesis from mRNAs. Investigating sequence characteristics of
      these signals is important, particularly to infer translational initiation
      mechanisms. Although various statistical analyses of translational initiation
      signals have been done, few have focused on base correlations that assess base
      dependencies in the signal sequences. We used relative entropy and mutual
      information to analyze base conservation and correlation, respectively, in the 5'
      UTRs of various species. In eukaryotes, we found peaks of relative entropy at -3
      from the translational start site but no peak of mutual information at that
      position, indicating that the base at that position (known as the core base of
      the Kozak sequence) is well conserved but not correlated with neighboring bases
      and thus functions as a single base. We observed unexpected peaks of mutual
      information between positions -2 and -1 in most eukaryotes. Surprisingly these
      base correlation also occurred in some bacteria and archaea, although there were
      no base preferences at neither position. Various dinucleotide patterns existed at
      these positions, and the correlation between bases at -2 and -1 may be relevant
      to the context of translational initiation. Because dinucleotide patterns of
      correlated pairs of nucleotides at -2 and -1 were not unique within respective
      organisms, the correlation could not be found when analyzing single-nucleotide
      conservation. Therefore, mutual information allowed us to discover signals that
      were not found by simply analyzing base conservation.

PMID- 16618532
TI  - A review of adjuvant therapy for resected primary gastric cancer with an update
      on Taegu's phase III trial with intraperitoneal chemotherapy.
AB  - AIMS: Because patients with advanced gastric cancers have less than 50% chance of
      cure after R0 resection, the need for an adjuvant treatment to eradicate residual
      microscopic disease is clear. The major treatment strategy during the last
      decades has been postoperative systemic therapy. The results of published trials
      were reviewed. And, perioperative intraperitoneal chemotherapy as an adjuvant to
      potentially curative surgery was evaluated. METHODS: A literature search on this
      topic was performed for articles relating to clinical trials using adjuvant
      chemotherapy in the management of gastric cancer. Subset analyses of Taegu's
      phase III trial of early postoperative intraperitoneal chemotherapy were
      performed. RESULTS: Even after extended lymphadenectomy, the peritoneal surface
      and resection site had a high incidence of recurrence. Postoperative systemic
      chemotherapy treatment regimens available in the past showed no major improvement
      in survival. One of new approaches currently undergoing study was intraperitoneal
      chemotherapy given in the perioperative period. The Taegu data showed this
      treatment reduced the incidence of peritoneal recurrence and thereby improved the
      survival rate after potentially curative surgery for gastric cancer. CONCLUSIONS:
      The eradication of micrometastatic foci in the peritoneal cavity can be achieved
      by the perioperative intraperitoneal administration of chemotherapeutic agents.
      Patients with serosa-positive gastric cancer are most likely to benefit from
      adjuvant intraperitoneal chemotherapy.

PMID- 16618533
TI  - Prediction of survival from carcinoma of oesophagus and oesophago-gastric
      junction following surgical resection using an artificial neural network.
AB  - AIM: The aim of this study was to assess the ability of artificial neural network
      (ANN) in predicting survival in patients undergoing surgical resection for
      carcinoma of oesophagus and oesophago-gastric junction. METHODS: From January
      1995 to August 2004 patients who underwent surgery for oesophageal and gastric
      carcinoma were identified. Biographical data, body mass index and pathological
      minimal cancer dataset were used to design an ANN. Post-operative survival was
      assessed at 1 and 3 years. Sixty percent of data was used to train and validate
      the ANN and 40% was used to evaluate the accuracy of trained ANN in predicting
      survival. This was compared with Union Internacional Contra la Cancrum UICC TNM
      classification system. RESULTS: Two hundred and sixteen patients underwent
      resectional surgery for oesophageal and OGJ carcinoma. The accuracy of the ANN in
      predicting survival at 1 and 3 years was 88% (sensitivity: 92.3%, specificity:
      84.5%, DP = 2.3) and 91.5% (sensitivity of 94.61%, specificity: 88%, DP = 2.72),
      respectively. These figures were significantly better than 1- and 3-year survival
      predictions using the UICC TNM classification system 71.6% (sensitivity of 66.4%,
      specificity: 75.5%, and DP < 1) and 74.7% (sensitivity of 70.5%, specificity:
      74.9%, DP < 1), respectively (P < 0.01) (P < 0.05). CONCLUSION: ANNs are superior
      to the UICC TNM classification system in correlating with survival following
      resection of carcinoma of oesophagus and OG junction and can become valuable
      tools in the management of patients with oesophageal carcinoma.

PMID- 16618534
TI  - Intraperitoneal chemotherapy with taxanes for ovarian cancer with peritoneal
      dissemination.
AB  - Paclitaxel and docetaxel are currently the two clinically available taxanes. The
      combination of a taxane and a platinum compound has become the systemic
      chemotherapy of choice for primary ovarian cancer. Despite the high activity of
      these drugs in systemic chemotherapy, the majority of patients with advanced
      ovarian cancer will develop recurrent disease and ultimately decease of this
      disease. Therefore, more effective systemic chemotherapy regimens or alternative
      treatment modalities are warranted. Intraperitoneal chemotherapy is such an
      alternative treatment option. Pharmacokinetic studies on intraperitoneal
      administration of paclitaxel and docetaxel demonstrated very high locoregional
      drug concentrations and exposure. Their activity and response seem to be dose
      dependent and hence higher efficacy with limited systemic toxicity is to be
      expected. Intraperitoneal chemotherapy may be combined intraoperatively with
      hyperthermia, which enhances tissue penetration and cytotoxic activity of many
      drugs. The data concerning thermal enhancement of taxanes are inconsistent, but
      at the high locoregional concentrations provided by intraperitoneal drug
      administration such a thermal enhancement seems to exist. Clinical studies have
      clearly demonstrated the feasibility and efficacy of intraperitoneal instillation
      chemotherapy with taxanes in patients with ovarian cancer. Preliminary results of
      a phase III study demonstrated improved outcome with the addition of
      intraperitoneal instillation chemotherapy to systemic chemotherapy after optimal
      primary cytoreductive surgery. Intraoperative hyperthermic intraperitoneal
      chemotherapy with docetaxel has been performed in a single study, in which
      promising results were observed. Further clinical investigations with an adequate
      follow-up period are needed to confirm the promising initial results and to
      determine the exact efficacy of intraperitoneal chemotherapy with these drugs.

PMID- 16618535
TI  - Goals and means in action observation: a computational approach.
AB  - Many of our daily activities are supported by behavioural goals that guide the
      selection of actions, which allow us to reach these goals effectively. Goals are
      considered to be important for action observation since they allow the observer
      to copy the goal of the action without the need to use the exact same means. The
      importance of being able to use different action means becomes evident when the
      observer and observed actor have different bodies (robots and humans) or bodily
      measurements (parents and children), or when the environments of actor and
      observer differ substantially (when an obstacle is present or absent in either
      environment). A selective focus on the action goals instead of the action means
      furthermore circumvents the need to consider the vantage point of the actor,
      which is consistent with recent findings that people prefer to represent the
      actions of others from their own individual perspective. In this paper, we use a
      computational approach to investigate how knowledge about action goals and means
      are used in action observation. We hypothesise that in action observation human
      agents are primarily interested in identifying the goals of the observed actor's
      behaviour. Behavioural cues (e.g. the way an object is grasped) may help to
      disambiguate the goal of the actor (e.g. whether a cup is grasped for drinking or
      handing it over). Recent advances in cognitive neuroscience are cited in support
      of the model's architecture.

PMID- 16618536
TI  - Dynamic and interactive generation of object handling behaviors by a small
      humanoid robot using a dynamic neural network model.
AB  - This study presents experiments on the learning of object handling behaviors by a
      small humanoid robot using a dynamic neural network model, the recurrent neural
      network with parametric bias (RNNPB). The first experiment showed that after the
      robot learned different types of ball handling behaviors using human direct
      teaching, the robot was able to generate adequate ball handling motor sequences
      situated to the relative position between the robot's hands and the ball. The
      same scheme was applied to a block handling learning task where it was shown that
      the robot can switch among learned different block handling sequences, situated
      to the ways of interaction by human supporters. Our analysis showed that
      entrainment of the internal memory structures of the RNNPB through the
      interactions of the objects and the human supporters are the essential mechanisms
      for those observed situated behaviors of the robot.

PMID- 16618537
TI  - New developments in lung function measurements in rodents.
AB  - There are invasive and noninvasive pulmonary function tests available which are
      sensitive in detecting bronchoconstriction in rodents. Noninvasively measured
      midexpiratory flow (EF50) has been shown to be an appropriate parameter to
      monitor bronchoconstriction in a large number of animals, e.g. for screening
      purposes. Recently, a novel technique for repetitive lung function measurements
      in orotracheally intubated, spontaneously breathing mice has been established.
      Bronchoconstriction is assessed by the "gold standard" parameters airway
      resistance and dynamic compliance in response to aerosolized methacholine or
      allergens in anesthetized mice. This measurement technique has been combined with
      an inhalation technique which has been optimized to allow simultaneous lung
      function measurement in intubated animals and to obtain high aerosol
      concentrations. A feedback dose control system has been developed to administer a
      defined and constant aerosol dose to each individual animal. Using this system a
      prominent early allergic response and late airway hyperresponsiveness could be
      demonstrated in intubated mice challenged with Aspergillus fumigatus allergen. We
      conclude: The noninvasive EF50 method seems particularly appropriate for
      measurements of respiratory function in large numbers of conscious mice in
      assembly line fashion. The invasive technology--newly established for the mouse-
      is more sensitive and specific since true airway resistance and dynamic
      compliance are determined and allows now the adequate detection of an early
      allergic response in the mouse and also repetitive measurements e.g. to assess
      the airway hyperresponsiveness in the same animal or for monitoring purposes in
      chronic models.

PMID- 16618538
TI  - Cyclooxygenase inhibitors not inhibit resting lung cancer A549 cell
      proliferation.
AB  - Cyclooxygenase (COX) inhibitors were regarded as anticarcinogenic agents for lung
      cancer at least partly via PGE2; but these were based on cytokin stimulation
      experiment on A549 cell. In order to clarify whether COX inhibitors directly
      inhibit A549 cell, three COX inhibitors, NS398 (selective COX-2 inhibitor), SC560
      (selective COX-1 inhibitor), and acetyl salicylic acid (ASA, non-selective COX
      inhibitor), were studied. NS398, and ASA, can inhibit PGE2 generation via COX-2
      inhibition. The viability of A549 cell was assayed by MTT. However, without
      cytokin stimulation, all the three inhibitors (NS398 0.2-20 microM; SC560 1.0-100
      nM; ASA 0.01-1.0 mM) were not able to inhibit A549 cell proliferation, in the
      other way round, NS398 promoted cell growth. And arachidonic acid (AA) and
      lipopolysaccharide (LPS) did not disturb the property of its growth. These data
      suggested that without cytokin stimulation, COX and PGE2 may not be the kernel
      molecules involved in A549 cell proliferation, and COX inhibitors could not
      inhibit A549 cell growth directly.

PMID- 16618539
TI  - Spontaneous recovery of diaphragmatic strength in unilateral diaphragmatic
      paralysis.
AB  - The aim of the present study was to evaluate diaphragmatic strength in patients
      with unilateral diaphragmatic paralysis and to determine whether patients with
      recent diaphragm paralysis develop lower inspiratory pressure than patients with
      longstanding diaphragmatic paralysis. Twenty patients (16 men and 4 women, 62+/
      12 years) and six control subjects were included (4 men and 2 women, 53+/-15
      years) in the study. Esophageal pressure during sharp sniff (Pes,sniff),
      bilateral cervical phrenic nerve magnetic stimulation (Pes,cms) and unilateral
      phrenic nerve stimulation (Pes,ums) (in nine patients) were measured. Sixteen
      patients presented right diaphragmatic paralysis and four, left diaphragmatic
      paralysis. Pes,sniff was higher in control subjects than in patients with
      diaphragmatic paralysis (respectively 110+/-22 cmH2O and 82+/-24 cmH2O, P<0.05).
      There was no difference in Pes,cms between patients with diaphragmatic paralysis
      and control subjects (14+/-7 cmH2O vs. 16+/-4 cmH2O; ns). Pes,ums after
      stimulation of the affected phrenic nerve was less than 4 cmH2O, was 8+/-2 cmH2O
      after stimulation of the intact phrenic nerve and was correlated to Pes,cms
      (R=0.87, P<0.01). There was a positive correlation between Pes,cms, Pes,ums of
      the intact hemidiaphragm, Pes,sniff and the time from the onset of symptoms and
      the diaphragmatic explorations (respectively R=0.86, P<0.0001; R=0.72, P<0.05;
      R=0.48, P<0.05). In conclusion, diaphragmatic strength after unilateral
      diaphragmatic paralysis seems to improve with time.

PMID- 16618540
TI  - Positive selection on gene expression in the human brain.

PMID- 16618541
TI  - MIG-10/lamellipodin and AGE-1/PI3K promote axon guidance and outgrowth in
      response to slit and netrin.
AB  - BACKGROUND: The cytoplasmic C. elegans protein MIG-10 affects cell migrations and
      is related to mammalian proteins that bind phospholipids and Ena/VASP actin
      regulators. In cultured cells, mammalian MIG-10 promotes lamellipodial growth and
      Ena/VASP proteins induce filopodia. RESULTS: We show here that during neuronal
      development, mig-10 and the C. elegans Ena/VASP homolog unc-34 cooperate to guide
      axons toward UNC-6 (netrin) and away from SLT-1 (Slit). The single mutants have
      relatively mild phenotypes, but mig-10; unc-34 double mutants arrest early in
      development with severe axon guidance defects. In axons that are guided toward
      ventral netrin, unc-34 is required for the formation of filopodia and mig-10
      increases the number of filopodia. In unc-34 mutants, developing axons that lack
      filopodia are still guided to netrin through lamellipodial growth. In addition to
      its role in axon guidance, mig-10 stimulates netrin-dependent axon outgrowth in a
      process that requires the age-1 phosphoinositide-3 lipid kinase but not unc-34.
      CONCLUSIONS: mig-10 and unc-34 organize intracellular responses to both
      attractive and repulsive axon guidance cues. mig-10 and age-1 lipid signaling
      promote axon outgrowth; unc-34 and to a lesser extent mig-10 promote filopodia
      formation. Surprisingly, filopodia are largely dispensable for accurate axon
      guidance.

PMID- 16618542
TI  - Standardization of 152Eu and 154Eu by 4pibeta-4pigamma coincidence method and
      4pi(beta+gamma) integral counting.
AB  - The 4pibeta-4pigamma coincidence counting and 4pi(beta+gamma) integral counting
      techniques were applied for the standardization of 152Eu and 154Eu. In these
      techniques, the beta-detector is composed of two thin plastic scintillators
      sandwiching the source coupled with a slender photomultiplier tube. This beta
      detector was inserted into a large well-type NaI(Tl) scintillation detector for
      gamma-ray detection, making a 4pibeta-4pigamma detector configuration. The
      results obtained by the above two techniques were in good agreement and
      consistent with the results of international comparisons.

PMID- 16618543
TI  - Design, spectrum measurements and simulations for a 238Pu alpha-particle
      irradiator for bystander effect and genomic instability experiments.
AB  - Design, spectrum measurements and simulations for an alpha-particle irradiator
      for bystander effect and genomic instability experiments are presented. Measured
      alpha-particle energy spectra were used to confirm the characteristics of the
      source of the irradiator specified by the manufacturer of the source. The spectra
      were measured in vacuum with a high-resolution spectrometer and simulated with an
      AASI Monte Carlo code. As a next step, we simulated alpha-particle energy spectra
      at the target plane of the irradiator for three different source-to-target
      distances. In these simulations, helium was used as the medium between the source
      and the exit window of the irradiator; its pressure and temperature corresponded
      to those of the ambient air. Mean energies and full-widths at half-maximum (FWHM)
      were calculated for the three different helium gas tracks.

PMID- 16618544
TI  - Automated, high-resolution cellular retention and uptake studies in vitro.
AB  - This report describes an automated method for the measurements of cellular
      retention and uptake of radiolabeled proteins interacting with cell-surface
      receptors on intact cancer cells. A complete uptake and retention measurement was
      performed in one cell dish using a rotating radioimmunoassay (RIA) principle.
      Compared to common manual measurements, rotating RIA saved both labor time and
      reagents and provided real-time binding traces with superior time-resolution. The
      rotating RIA retention profiles for different interactions agreed with retention
      times reported in the literature.

PMID- 16618545
TI  - High-energy resolution alpha spectrometry using cryogenic detectors.
AB  - Applications such as environment monitoring implying alpha emitters activity
      measurement associated with isotope identification, require high-energy
      resolution detectors. Conventional silicon detectors are inexpensive therefore
      widely used, although intrinsically limited in energy resolution. Thermal
      detection principle of cryogenic detectors introduces a breakthrough in alpha
      particle measurement. For the first time, spectra with 5.5 keV FWHM energy
      resolution have been obtained for several external alpha emitting sources using a
      copper-germanium bolometer specially developed for alpha spectrometry.

PMID- 16618546
TI  - A new attachment for proximal segment positioning for bimaxillary dysgnathic
      surgery--technical note.
AB  - BACKGROUND: The frequent insertion of self-tapping screws for securing the
      proximal positioning plate in bimaxillary osteotomy often cause loosening of
      screws and plate, which produces incorrect repositioning. In this article, a
      newly developed base-attachment for a T-shaped proximal positioning plate for
      bimaxillary osteotomy is presented. MATERIAL: The base-attachment set consists of
      a titanium base-attachment and two titanium tapped screws. The attachment has a
      shallow depression having the same shape as the basal part of the positioning
      plate. METHOD: The base-attachment is secured by self-tapping screws until the
      end of the procedure, and the T-shaped proximal positioning plate is placed and
      secured by two titanium-tapped screws. RESULT: By using this base-attachment, the
      T-shaped plate can be easily placed repeatedly without difficulty. CONCLUSION:
      This base-attachment set may be useful for the frequently repositioned proximal
      plate in bimaxillary osteotomy.

PMID- 16618547
TI  - The Belfast approach to managing complex lower limb vascular injuries.
AB  - INTRODUCTION: Complex lower limb vascular injuries (CLVIs) in high-energy
      penetrating or blunt trauma are associated with an unacceptably high incidence of
      complications including amputation. Traumatic ischaemia and ischaemia-reperfusion
      injury (IRI) of skeletal muscle often lead to limb loss, the systemic
      inflammatory response syndrome (SIRS) which affects remote organs and even the
      potentially fatal multiple organ dysfunction syndrome (MODS). Surgical care of
      CLVIs everywhere, including Northern Ireland until 1978, was governed by an
      anxiety to restore arterial flow quickly often using expedient and flawed repair
      techniques while a damaged major vein was frequently ligated. MATERIALS AND
      METHODS: A new policy centred on early intraluminal shunting of both artery and
      vein, restoring arterial inflow and venous outflow, respectively, was introduced
      at the Regional Vascular Surgery Unit of The Royal Victoria Hospital, Belfast in
      1979. It imposed a disciplined one-stage comprehensive approach to treatment
      involving a sequence of operative manoeuvres in which all damaged anatomical
      elements receive meticulous and optimal attention unshackled by time constraints.
      RESULTS: Comparisons drawn between the pre-shunt period of unplanned treatment
      (1969-1978) and the post-shunt period centred on the use of shunts (1979-2000)
      showed that early shunting of both artery and vein in both penetrating (P) and
      blunt (B) injuries significantly reduced the necessity for fasciotomy (P:
      p=0.016, B: p=0.02) and caused a significant fall in the incidence of contracture
      (P: p=0.018, B: p=0.02) and of amputation (P: p=0.009, P: p=0.012). CONCLUSIONS:
      The policy of early shunting of artery and vein in CLVIs has proved to be of
      great benefit in terms of significantly improved outcomes, better operative
      discipline and harmonious collaboration among the specialists involved.

PMID- 16618548
TI  - Sleep, rhythms and women's mood. Part II. Menopause.
AB  - This review summarizes studies of sleep and other biological rhythms in
      menopausal women with major depression compared with healthy control subjects.
      Where feasible, we focused on studies in women who met DSM-IV (Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition) criteria for a major
      depressive episode (MDE) compared with matched normal control subjects and the
      Staging System for Reproductive Aging in Women (STRAW) criteria. The aim was to
      review supporting evidence for the hypothesis that a disruption of the normal
      temporal relationship between sleep and other biological rhythms, such as
      melatonin, cortisol, thyroid stimulating hormone (TSH) or prolactin, occur during
      the menopausal transition. As a result, depressive disorders occur in predisposed
      women. Treatment strategies, designed to correct these altered phase (timing) or
      amplitude abnormalities, thereby improve mood. Although there may be some common
      features to menopausal depression compared with other depressive disorders
      related to the reproductive cycle (e.g. premenstrual dysphoric disorder or
      postpartum major depression), such as increased morning melatonin secretion, a
      specific profile of sleep and biological rhythms may distinguish healthy from
      depressed women during menopause. Further work is needed to characterize more
      fully the particular abnormalities associated with well-defined menopausal
      depression in order to develop treatment strategies targeted more specifically to
      pathogenesis.

PMID- 16618549
TI  - In vivo kinetics with rapid perturbation experiments in Saccharomyces cerevisiae
      using a second-generation BioScope.
AB  - We present a robust second-generation BioScope: a system for continuous
      perturbation experiments. Firstly, the BioScope design parameters (i.e., pressure
      drop, overall oxygen (O2) and carbon dioxide (CO2) mass transfer, mean residence
      time distribution and plug flow characteristics) were evaluated. The average
      overall mass transfer coefficients were estimated to be 1.8E-5 m s(-1) for O2 and
      0.34E-5 m s(-1) for CO2. It was determined that the O2/CO2 permeable membrane
      accounted for 75% and 95% of the overall resistance for O2 and CO2, respectively.
      The Peclet number (Pe) of the system was found to be >500 for liquid flow rates
      between 1 and 4 ml min(-1), ensuring plug flow characteristics. Secondly, steady
      state intracellular metabolite concentrations obtained using direct rapid
      sampling from the fermentor were compared with those obtained by rapid sampling
      via the pre-perturbation sample port of the BioScope. With both methods the same
      metabolite levels were obtained. Thirdly, glucose perturbation experiments were
      carried out directly in the fermentor as well as in the BioScope, whereby steady
      state Saccharomyces cerevisiae cells from a glucose/ethanol limited chemostat
      were perturbed by increasing the extracellular glucose concentration from 0.11 to
      2.8 mM. Intracellular and extracellular metabolite levels were measured within a
      time window of 180 s. It was observed that the dynamic metabolite concentration
      profiles obtained from both perturbations were nearly the same, with the
      exception of the C4 metabolites of the TCA cycle, which might be due to
      differences in culture age.

PMID- 16618550
TI  - Evidence from SSU rRNA phylogeny that Octomitus is a sister lineage to Giardia.
AB  - Octomitus intestinalis is a diplomonad flagellate inhabiting the digestive tract
      of rodents and amphibians. Octomitus is of evolutionary interest because, based
      on ultrastructural characteristics, it is thought to be closely related to the
      morphologically derived genus Giardia, and together they have been proposed to
      make up the Giardiinae. In molecular trees of diplomonads, Giardia is the deepest
      branching lineage, so identifying a sister group to Giardia that is less derived
      would be informative. Octomitus is a logical candidate for this position, but
      unfortunately there are no molecular data from it, and it is not available in
      culture. To determine the position of Octomitus, and specifically test whether it
      is more closely related to Giardia than other diplomonads, we have isolated it
      directly from the caecum of wild mice and characterized its small subunit
      ribosomal RNA (SSU rRNA) gene. Phylogenetic analysis showed Octomitus to be the
      sister to Giardia with strong support, together occupying one side of the deepest
      split in the diplomonad tree.

PMID- 16618551
TI  - Molecular diversity of dinoflagellate symbionts of Cnidaria: the psbA minicircle
      of Symbiodinium.
AB  - Dinoflagellate algae of the genus Symbiodinium are important symbionts within
      corals and other benthic marine animals. The molecular diversity of Symbiodinium
      has been described mainly by use of ribosomal DNA sequence data. We tested
      whether minicircle sequences, which appear to form the chloroplast genome in many
      dinoflagellates, could be used as a marker for molecular diversity among
      symbionts found in corals and sea anemones. Partial and full-length sequences for
      psbA were obtained from environmental samples of coral and sea anemones of wide
      ranging geographical distribution. Phylogenetic trees constructed with partial
      psbA sequences were consistent with the known phylotypes of the isolates. Further
      sequencing suggested that the psbA gene is present on a minicircle in all
      Symbiodinium phylotypes. The length and DNA sequence of the non-coding portion of
      the minicircles varied considerably among Symbiodinium phylotypes. In two
      Symbiodinium isolates from different phylotypes an elaborate pattern of repeat
      sequences of unknown function was found in the non-coding region. Phylogenetic
      analysis of the non-coding region of the psbA minicircle indicates that
      minicircle sequences could be a useful chloroplast-derived marker for
      differentiating both closely related and distantly related Symbiodinium isolates.

PMID- 16618552
TI  - Concert of regulators to switch on LEE expression in enterohemorrhagic
      Escherichia coli O157:H7: interplay between Ler, GrlA, HNS and RpoS.
AB  - Enterohemorrhagic (EHEC) and enteropathogenic (EPEC) Escherichia coli strains
      carry a pathogenicity island termed locus of enterocyte effacement (LEE)
      responsible for attaching and effacing lesions on epithelial cells. The
      expression of LEE varies among isolates and is dependent on environmental cues.
      In the EHEC O157:H7 Sakai isolate (RIMD-0509952 strain), we found that the non
      coding RNA, DsrA, activates the expression of the LEE. This activation requires
      RpoS, the stress sigma factor. The DsrA/RpoS regulatory pathway mediates its
      positive effect by stimulating the transcription of ler, a positive regulatory
      gene encoded by the LEE. A second regulatory pathway, repressed by HNS, is also
      able to activate the transcription of ler and requires GrlA, another LEE-encoded
      regulator. Both regulatory pathways, DsrA/RpoS and HNS/GrlA, affect the activity
      of the ler distal promoter and require the Ler protein to be functional. Our data
      demonstrate that the LEE expression can be turned on by at least two separate
      pathways acting on the transcription of ler.

PMID- 16618553
TI  - Mycobacterium bovis in rural Tanzania: risk factors for infection in human and
      cattle populations.
AB  - Although bovine tuberculosis is widespread throughout Africa, very little is
      known about risk factors for Mycobacterium bovis infection in either human or
      cattle populations. A human case-control study was conducted in northern
      Tanzania, comparing risk factors and prevalence of cattle interdermal test
      positives of cases (cervical adenitis cases from which M. bovis was isolated)
      with age- and sex-matched controls (selected at random from potential hospital
      attendees within the community). A cattle cross-sectional study was also set-up
      involving 27 villages selected at random in four districts, with 10,549 cattle
      and 622 herds tested, and questionnaire surveys conducted in 239 households. M.
      bovis was confirmed in seven of 65 (10.8%) human cervical adenitis cases, of
      which only one came from a household owning infected cattle. M. bovis in human
      patients was associated with families in which a confirmed diagnosis of
      tuberculosis had previously been made (p<0.001) and with households far (>100m)
      from neighbours (p=0.003). In cattle, overall prevalence of intradermal test
      positives was low at 0.9% (0.70-1.06%), but widespread, with 11.8% (8.44-13.17%)
      herds containing at least one reactor. Prevalence of intradermal test positives
      increased significantly with cattle age (p<0.001). Herds with the following risk
      factors had a significantly greater prevalence of intradermal test positives: >50
      cattle in the herd (p=0.024); herds housed inside at night (p=0.021) and herds in
      contact with wildlife (p=0.041). Furthermore, villages that experienced annual
      flooding had a higher prevalence of infection (p=0.043).

PMID- 16618554
TI  - Transdermal delivery of drugs for urologic applications: basic principles and
      applications.

PMID- 16618555
TI  - The camera phone: a novel aid in urologic practice.
AB  - OBJECTIVES: To describe a novel use of the camera phone for efficient, reliable,
      and cost-effective collection and transmission of medical data in the urologic
      setting. METHODS: We used camera phones (Verizon VGA and Sanyo-Sprint PCS) with a
      resolution of 640 x 480 pixels to capture images in the operating room, as well
      as in the outpatient clinic. Images were obtained directly from the monitor or
      the x-ray viewing box. These were then immediately transmitted to the office
      computer through a secure Internet connection. The images were then incorporated
      into operative and office notes, as needed. RESULTS: The images obtained with
      this method were of adequate quality for demonstration purposes, with the added
      advantage of allowing secure transmission and storage. The best-quality images
      were those obtained directly from the x-ray viewing box or from a liquid crystal
      display monitor. In addition, the images could be edited and labels added with
      the aid of the software that came with the camera phone. CONCLUSIONS: This method
      allows the acquisition of fair-quality digital images of surgical procedures and
      radiographic studies with simultaneous data transmission and storage for clinical
      documentation. The technology reduced costs and increased the efficiency of our
      practice considerably.

PMID- 16618556
TI  - Fibrin sealant as tissue glue: preliminary experience in complex genital
      reconstructive surgery.
AB  - OBJECTIVES: To report the outcomes of graft take and wound healing in the first
      reported series in which fibrin sealant was used as a tissue glue in the
      reconstruction of complex genital skin loss. METHODS: Between July 2001 and July
      2005, 18 men requiring complex genital reconstruction underwent repair by two
      surgeons at our medical centers. Skin graft reconstruction was required in 6 men.
      Complete scrotal disassembly with extensive scrotal or thigh flaps was required
      for reconstruction of 12 others. In the skin graft cases, a thin layer of dilute
      fibrin sealant was sprayed on the recipient site immediately before graft
      apposition. In flap cases, fibrin sealant was injected beneath the flap to
      promote tissue adherence and prevent fluid accumulation. All wounds were followed
      up postoperatively and observed for evidence of graft take, seroma or hematoma
      formation, drainage, and infection. RESULTS: The 6 skin graft patients required a
      total of nine split-thickness skin grafts, all of which had 100% take. Of the 12
      patients requiring flap reconstruction, 11 had excellent results. One flap case
      had a partial wound breakdown, but this reconstruction was performed immediately
      subsequent to a significant debridement and irrigation procedure in the same
      setting. Overall, 17 (94.4%) of 18 patients had no wound infection, seroma,
      hematoma, or other complications. CONCLUSIONS: Fibrin sealant performs very well
      as a tissue glue and appears to be a useful adjunct in cases of complex genital
      skin loss reconstruction.

PMID- 16618559
TI  - Is there a role for periurethral collagen injection in the management of
      urodynamically proven mixed urinary incontinence?
AB  - OBJECTIVES: To investigate the effectiveness of periurethral collagen injection
      (PCI) in patients presenting with symptoms of mixed urinary incontinence (MUI)
      and urodynamically demonstrated sphincter deficiency and detrusor overactivity.
      METHODS: A retrospective review was performed on all patients undergoing PCI from
      February 1999 to February 2003, during which those with MUI were treated with PCI
      as first-line therapy. The inclusion criteria were MUI symptoms, detrusor
      overactivity on urodynamic study, stress urinary incontinence due to sphincter
      deficiency (determined from physical examination, stress test, urodynamic study
      with Valsalva leak point pressure, and cystography findings, without urethral
      hypermobility). The primary outcome measures were the Urogenital Distress
      Inventory (UDI), Incontinence Impact Questionnaire, and quality-of-life score and
      the need for anticholinergic medications or additional surgery. Comparisons were
      performed using the Wilcoxon signed ranks test and paired t test. RESULTS: Of the
      56 patients who underwent PCI, 43 presented with symptoms of MUI, and 16 of these
      (29%) had both detrusor overactivity and stress urinary incontinence on
      urodynamic study. The mean follow-up after PCI (without additional PCI) was 18
      months (range 6 to 39). The mean age was 65 years (range 40 to 84). The mean
      Valsalva leak point pressure was 54 +/- 40 cm H2O (range 18 to 146). Ten patients
      had undergone previous anti-incontinence procedures, and anticholinergic
      medications had failed in six. The questionnaire scores, indicating severe
      MUI/poor quality of life before PCI, improved after PCI: UDI question 1, 2.3 +/-
      0.8 versus 1.3 +/- 1.0 (P = 0.021); UDI question 2, 2.1 +/- 1.2 versus 1.4 +/-
      1.0 (P = 0.068); UDI question 3, 2.9 +/- 0.4 versus 1.8 +/- 1.2 (P = 0.010); and
      quality-of-life question, 8.6 +/- 2.1 versus 5.2 +/- 3.5 (P = 0.026). The mean
      injected volume/patient was 8.5 cm3 (range 5 to 17) within a mean of 1.9
      treatments (range 1 to 3). Four patients continued taking anticholinergic
      medications and one proceeded to sling placement. CONCLUSIONS: The use of PCI as
      the primary/initial intervention in patients with MUI may be the preferred
      approach, particularly in patients with an elevated risk of anticholinergic
      medication side effects or when voiding dynamics preclude sling placement.

PMID- 16618562
TI  - Nighttime dosing with tolterodine reduces overactive bladder-related nocturnal
      micturitions in patients with overactive bladder and nocturia.
AB  - OBJECTIVES: To evaluate the efficacy and tolerability of nighttime tolterodine
      dosing on urgency-related micturitions in patients with overactive bladder (OAB)
      and nocturia. METHODS: This was a 12-week randomized controlled study of 850
      patients given 4 mg tolterodine extended release (TER) or placebo once daily 4
      hours or less before bed. Patients with eight or more micturitions/24 hours and a
      mean of 2.5 episodes/night or more were included. Changes in the number of
      nighttime and 24-hour micturitions were analyzed by urgency rating per
      micturition. The urgency per micturition was recorded in 7-day diaries using a 5
      point rating scale (score 1 to 5). Each micturition was classified according to
      the following urgency rating categories: total (1 to 5), non-OAB (1 to 2), or OAB
      (3 to 5). OAB-related micturitions were further classified as nonsevere (score 3)
      and severe (score 4 to 5). RESULTS: TER reduced the total number of nocturnal
      micturitions, but, compared with placebo, this difference was not statistically
      significant. However, TER did significantly reduce OAB-related and severe OAB
      related nocturnal micturitions compared with placebo. TER had no effect on non
      OAB micturitions. TER significantly reduced the total, OAB, and severe OAB
      micturitions during 24-hour and daytime intervals compared with placebo.
      Significantly more TER-treated than placebo-treated patients reported a treatment
      benefit and willingness to continue treatment. Adverse events associated with
      nighttime dosing of TER versus placebo were few. CONCLUSIONS: TER significantly
      reduced OAB-related micturitions during 24-hour, daytime, and nighttime
      intervals. TER did not affect normal (non-OAB) micturitions. Nighttime dosing
      with TER was associated with few adverse events and adverse event-related
      withdrawals. The 24-hour efficacy of TER was maintained with nighttime dosing.

PMID- 16618564
TI  - Radical cystectomy after bacillus Calmette-Guerin for high-risk Ta, T1, and
      carcinoma in situ: defining the risk of initial bladder preservation.
AB  - OBJECTIVES: To critically evaluate the survival of patients with high-grade Ta or
      T1 urothelial cancer (UC) or carcinoma in situ of the bladder who have received
      bacillus Calmette-Guerin (BCG) and who have undergone radical cystectomy.
      METHODS: We retrospectively reviewed our single-surgeon database of those
      patients who underwent cystectomy and previously received BCG. We evaluated the
      baseline characteristics, pathologic outcomes, and survival data. RESULTS: Of 313
      patients who underwent cystectomy between January 1992 and March 2004, 90 (29%)
      received BCG before bladder removal. The mean time from the first BCG course to
      the date of cystectomy was 27.9 months. The mean duration of follow-up from
      cystectomy was 32.1 months. The risk of progression to muscle invasion for those
      who underwent cystectomy less than or more than 1 year from the time of their
      first BCG dose was 59% and 36%, respectively (P = 0.05). The disease-specific
      survival rate was 81% versus 80% for those who underwent early versus delayed
      cystectomy (P = 0.9). CONCLUSIONS: Patients with high-grade UC are at risk of
      dying from this cancer, even if they ultimately undergo cystectomy. Patients who
      receive BCG should be appropriately counseled that they remain at risk for
      disease progression and death from UC. It is difficult to ascertain the proper
      time to proceed with cystectomy if an initial bladder conservation approach is
      used.

PMID- 16618565
TI  - Renal expression of epidermal growth factor and transforming growth factor-beta1
      in children with congenital hydronephrosis.
AB  - OBJECTIVES: To study the potential role of pelviureteral junction obstruction
      (PUJO) in causing progressive renal damage in children through the renal
      expression of epidermal growth factor (EGF) and transforming growth factor-beta1
      (TGF-beta1). METHODS: The expression of EGF and TGF-beta1 was evaluated in the
      renal tissues of 25 children with congenital hydronephrosis by
      immunohistochemistry, in situ hybridization, and reverse transcriptase polymerase
      chain reaction techniques. RESULTS: Children with PUJO had a significant increase
      in TGF-beta1 and a marked reduction in EGF expression compared with controls. The
      TGF-beta1/glyceraldehyde phosphate dehydrogenase ratio in the hydronephrotic
      kidney and normal kidney was 0.53 +/- 0.13 and 0.24 +/- 0.10 respectively, and
      the difference was significant (P = 0.000). The EGF/glyceraldehyde phosphate
      dehydrogenase ratio in the hydronephrotic kidney and normal kidney was 0.15 +/-
      0.06 and 0.55 +/- 0.13, respectively, and the difference was also significant (P
      = 0.0001). Positive correlations were found between the TGF-beta1 gene and the
      drainage clearance half-time (r = 0.47; P = 0.018), TGF-beta1 protein and
      drainage clearance half-time (r = 0.44; P = 0.028), TGF-beta1 gene and histologic
      grade (r = 0.53; P = 0.006), and TGF-beta1 protein and histologic grade (r =
      0.76; P = 0.000). Negative correlations were found between the EGF gene and
      drainage clearance half-time (r = -0.59; P = 0.002), EGF protein and drainage
      clearance half-time (r = -0.61; P = 0.001), EGF gene and histologic grade (r = 
      0.58; P = 0.003), and EGF protein and histologic grade (r = -0.47; P = 0.019).
      CONCLUSIONS: TGF-beta1 expression was increased and EGF expression was decreased
      in the renal tissue after clinical PUJO. The alterations of TGF-beta1 and EGF may
      play a potential role in the pathogenesis of renal damage in PUJO.

PMID- 16618568
TI  - Experience with fibrin glue in bulbar urethral reconstruction using dorsal buccal
      mucosa graft.
AB  - Buccal mucosa dorsal onlay graft urethroplasty represents a widespread method for
      bulbar urethral stricture repair. We describe a modified procedure with the use
      of fibrin glue applied on the receiving bed before graft location.

PMID- 16618569
TI  - Laparoscopic transvesical urethrorectal fistula repair: a new technique.
AB  - INTRODUCTION: Urethrorectal fistulas are rare, and several open operative
      approaches and techniques have been used in treatment. We report our preliminary
      experience with laparoscopic transvesical urethrorectal fistula repair after
      iatrogenic urethrorectal fistula. A 65-year-old man with insulin-dependent
      diabetes mellitus and peripheral vascular disease was hospitalized 6 months after
      transurethral resection of the prostate for benign prostatic hyperplasia with a
      recurrent urinary tract infection, fecaluria, and urine leakage from the rectum
      during voiding. Urethrocystoscopy revealed a urethrorectal fistula in the
      prostatic fossa. Primary conservative treatment failed. TECHNICAL CONSIDERATIONS:
      The patient was placed in the lithotomy position, and the suprapubic tract was
      dilated to allow a 10-mm telescope. Carbon dioxide gas was used to distend the
      bladder (15 mm Hg, flow rate 3 L/min). Next, two 3-mm pediatric trocars were
      inserted under direct vision. The fistula was identified and the edge of the
      fistula excised. A running suture (3-0 PDS, RB needle) was used to close the
      fistula. Finally, a 16F Foley urethral catheter was passed under direct vision,
      followed by a suprapubic catheter. On postoperative day 12, retrograde
      cystography revealed no contrast leakage from the rectum. Follow-up after 3
      months showed no recurrence of the fistula. CONCLUSIONS: A transvesical
      laparoscopic technique might be useful for selective cases of urethrorectal
      fistula. Other methods of laparoscopic urethrorectal fistula repair have included
      bivalving of the bladder and omental interposition. The laparoscopic transvesical
      approach provides many advantages, including easy access and identification of
      the fistula tract, good surgical exposure, and minimal tissue manipulation.

PMID- 16618570
TI  - Laparoscopic en bloc partial cystectomy with bilateral pelvic lymphadenectomy for
      urachal adenocarcinoma.
AB  - INTRODUCTION: Surgical options for treating urachal adenocarcinoma include
      radical cystectomy and en bloc partial cystectomy with excision of the urachus
      and umbilectomy. Recently, laparoscopy has been increasingly used to treat
      bladder and urachal pathologic findings efficaciously. We describe two techniques
      for performing laparoscopic en bloc partial cystectomy with bilateral extended
      pelvic lymphadenectomy. TECHNICAL CONSIDERATIONS: We performed the procedure in 3
      patients with established urachal adenocarcinoma. The anatomic boundaries of
      resection were similar to those described for open surgery. We used an inverted V
      shaped, five-port configuration, with the camera port placed 3 cm
      supraumbilically. An antegrade approach was performed for tumors less than 5 cm
      in 2 cases. The steps of the procedure included an inverted V-shaped incision
      along the peritoneum lateral to the medial umbilical ligament on either side;
      urachal disconnection, dissection of the urachus using the "twist and roll
      technique"; anterior cystotomy, circumferential resection of the tumor-bearing
      bladder dome, under vision; tumor placement in a "lap-bag"; bladder
      reconstruction using intracorporeal suturing; bilateral extended pelvic
      lymphadenectomy; placement of catheter and drain; and specimen retrieval. We
      evolved a retrograde technique for larger size tumors (larger than 5 cm). The
      procedure was successfully completed in all patients, with a mean operative time
      of 180 minutes (range 150 to 210). No significant intraoperative or postoperative
      complications occurred, except for a left inferior epigastric artery injury in 1
      case. The resected nodes (range 8 to 11) were free of tumor. No local or distant
      recurrences were observed at a mean follow-up of 6.5 months (range 4.5 to 9).
      CONCLUSIONS: Laparoscopic en bloc partial cystectomy and bilateral extended
      pelvic lymphadenectomy is a safe, feasible, minimally invasive alternative to
      open partial cystectomy for urachal tumors.

PMID- 16618571
TI  - Resorbable clip migration in the collecting system after laparoscopic partial
      nephrectomy.
AB  - A complication is reported in which Lapra-Ty absorbable suture clips (Ethicon
      EndoSurgery) migrated from a laparoscopic partial nephrectomy bed into the
      collecting system, causing renal colic. During surgery performed with hilar
      occlusion, visual inspection did not reveal collecting system entry. Transected
      vessels were oversewn with absorbable suture secured with Lapra-Tys. Absorbable
      bolsters were placed in the parenchymal bed, and compression sutures secured with
      Lapra-Tys were placed through the renal capsule. Six weeks postoperatively, the
      patient developed ipsilateral renal colic, and computed tomography demonstrated
      several 3-mm opacities within the ureter. After 2 weeks of conservative
      management, he spontaneously passed several Lapra-Ty clips.

PMID- 16618572
TI  - Intensity-modulated radiation therapy, protons, and the risk of second cancers.
AB  - Intensity-modulated radiation therapy (IMRT) allows dose to be concentrated in
      the tumor volume while sparing normal tissues. However, the downside to IMRT is
      the potential to increase the number of radiation-induced second cancers. The
      reasons for this potential are more monitor units and, therefore, a larger total
      body dose because of leakage radiation and, because IMRT involves more fields, a
      bigger volume of normal tissue is exposed to lower radiation doses. Intensity
      modulated radiation therapy may double the incidence of solid cancers in long
      term survivors. This outcome may be acceptable in older patients if balanced by
      an improvement in local tumor control and reduced acute toxicity. On the other
      hand, the incidence of second cancers is much higher in children, so that
      doubling it may not be acceptable. IMRT represents a special case for children
      for three reasons. First, children are more sensitive to radiation-induced cancer
      than are adults. Second, radiation scattered from the treatment volume is more
      important in the small body of the child. Third, the question of genetic
      susceptibility arises because many childhood cancers involve a germline mutation.
      The levels of leakage radiation in current Linacs are not inevitable. Leakage can
      be reduced but at substantial cost. An alternative strategy is to replace X-rays
      with protons. However, this change is only an advantage if the proton machine
      employs a pencil scanning beam. Many proton facilities use passive modulation to
      produce a field of sufficient size, but the use of a scattering foil produces
      neutrons, which results in an effective dose to the patient higher than that
      characteristic of IMRT. The benefit of protons is only achieved if a scanning
      beam is used in which the doses are 10 times lower than with IMRT.

PMID- 16618573
TI  - Digital tomosynthesis with an on-board kilovoltage imaging device.
AB  - PURPOSE: To generate on-board digital tomosynthesis (DTS) and reference DTS
      images for three-dimensional image-guided radiation therapy (IGRT) as an
      alternative to conventional portal imaging or on-board cone-beam computed
      tomography (CBCT). METHODS AND MATERIALS: Three clinical cases (prostate, head
      and-neck, and liver) were selected to illustrate the capabilities of on-board DTS
      for IGRT. Corresponding reference DTS images were reconstructed from digitally
      reconstructed radiographs computed from planning CT image sets. The effect of
      scan angle on DTS slice thickness was examined by computing the mutual
      information between coincident CBCT and DTS images, as the DTS scan angle was
      varied from 0 degrees to 165 degrees . A breath-hold DTS acquisition strategy was
      implemented to remove respiratory motion artifacts. RESULTS: Digital
      tomosynthesis slices appeared similar to coincident CBCT planes and yielded
      substantially more anatomic information than either kilovoltage or megavoltage
      radiographs. Breath-hold DTS acquisition improved soft-tissue visibility by
      suppressing respiratory motion. CONCLUSIONS: Improved bony and soft-tissue
      visibility in DTS images is likely to improve target localization compared with
      radiographic verification techniques and might allow for daily localization of a
      soft-tissue target. Breath-hold DTS is a potential alternative to on-board CBCT
      for sites prone to respiratory motion.

PMID- 16618575
TI  - Modeling radiation pneumonitis risk with clinical, dosimetric, and spatial
      parameters.
AB  - PURPOSE: To determine the clinical, dosimetric, and spatial parameters that
      correlate with radiation pneumonitis. METHODS AND MATERIALS: Patients treated
      with high-dose radiation for non-small-cell lung cancer with three-dimensional
      treatment planning were reviewed for clinical information and radiation
      pneumonitis (RP) events. Three-dimensional treatment plans for 219 eligible
      patients were recovered. Treatment plan information, including parameters
      defining tumor position and dose-volume parameters, was extracted from non
      heterogeneity-corrected dose distributions. Correlation to RP events was assessed
      by Spearman's rank correlation coefficient (R). Mathematical models were
      generated that correlate with RP. RESULTS: Of 219 patients, 52 required treatment
      for RP (median interval, 142 days). Tumor location was the most highly correlated
      parameter on univariate analysis (R = 0.24). Multiple dose-volume parameters were
      correlated with RP. Models most frequently selected by bootstrap resampling
      included tumor position, maximum dose, and D35 (minimum dose to the 35% volume
      receiving the highest doses) (R = 0.28). The most frequently selected two- or
      three-parameter models outperformed commonly used metrics, including V20
      (fractional volume of normal lung receiving >20 Gy) and mean lung dose (R =
      0.18). CONCLUSIONS: Inferior tumor position was highly correlated with
      pneumonitis events within our population. Models that account for inferior tumor
      position and dosimetric information, including both high- and low-dose regions
      (D(35), International Commission on Radiation Units and Measurements maximum
      dose), risk-stratify patients more accurately than any single dosimetric or
      clinical parameter.

PMID- 16618574
TI  - Development of a statewide hospital plan for radiologic emergencies.
AB  - Although general guidelines have been developed for triage of victims in the
      field and for hospitals to plan for a radiologic event, specific information for
      clinicians and administrators is not available for guidance in efficient
      management of radiation victims during their early encounter in the hospital. A
      consensus document was developed by staff members of four Connecticut hospitals,
      two institutions of higher learning, and the State of Connecticut Department of
      Environmental Protection and Office of Emergency Preparedness, with assistance of
      the American Society for Therapeutic Radiology and Oncology. The objective was to
      write a practical manual for clinicians (including radiation oncologists,
      emergency room physicians, and nursing staff), hospital administrators, radiation
      safety officers, and other individuals knowledgeable in radiation monitoring that
      would be useful for evaluation and management of radiation injury. The rationale
      for and process by which the radiation response plan was developed and
      implemented in the State of Connecticut are reviewed. Hospital admission pathways
      are described, based on classification of victims as exposed, contaminated,
      and/or physically injured. This manual will be of value to those involved in
      planning the health care response to a radiologic event.

PMID- 16618576
TI  - Spanish patterns of care for 3D radiotherapy in non-small-cell lung cancer.
AB  - PURPOSE: Curative radiotherapy for non-small-cell lung cancer is a difficult
      challenge, despite the use of conformal radiotherapy. Optimal three-dimensional
      delineation of treatment volumes is essential for improvement of local control
      and for limiting of tissue toxicity. MATERIAL AND METHODS: A planning course on
      clinical practice of lung cancer was held in Barcelona. A questionnaire was given
      concerning (1) patient positioning, (2) planning-computed tomography scan, (3)
      accounting for tumor mobility, (4) investigative-procedure respiration-gated
      radiotherapy and breath-holding maneuvers, (5) generation of target volumes, (6)
      treatment planning, and (7) treatment delivery. This questionnaire was made to
      determine the Spanish application of European recommendations. RESULTS: On the
      negative side, 1 hospital did not use three-dimensional tools, less than 50% used
      immobilization devices, and 55.6% used computed tomography slices of greater than
      5 mm. On the positive side, 70.4% did not use standard margins for gross target
      volume derived from a computed tomography scan, 92.6% agreed with the inclusion
      of Naruke anatomic criteria of 1 cm or more in gross target volume planning, and
      75% used V20 to estimate the risk of pneumonitis. CONCLUSIONS: This study is the
      first validation of European recommendations for treatment planning and execution
      of radiotherapy in lung cancer. The main conclusion is the need to improve the
      negative aspects determined.

PMID- 16618577
TI  - Initial experience of FDG-PET/CT guided IMRT of head-and-neck carcinoma.
AB  - PURPOSE: The purpose of this study is to evaluate the impact of (18)F
      fluorodeoxyglucose positron emission tomography (FDG-PET) fused with planning
      computed tomography (CT) on tumor localization, which guided intensity-modulated
      radiotherapy (IMRT) of patients with head-and-neck carcinoma. METHODS AND
      MATERIALS: From October 2002 through April 2005, we performed FDG-PET/CT guided
      IMRT for 28 patients with head-and-neck carcinoma. Patients were immobilized with
      face masks that were attached with five fiducial markers. FDG-PET and planning CT
      scans were performed on the same flattop table in one session and were then
      fused. Target volumes and critical organs were contoured, and IMRT plans were
      generated based on the fused images. RESULTS: All 28 patients had abnormal
      increased uptake in FDG-PET/CT scans. PET/CT resulted in CT-based staging changes
      in 16 of 28 (57%) patients. PET/CT fusions were successfully performed and were
      found to be accurate with the use of the two commercial planning systems. Volume
      analysis revealed that the PET/CT-based gross target volumes (GTVs) were
      significantly different from those contoured from the CT scans alone in 14 of 16
      patients. In addition, 16 of 28 patients who were followed for more than 6 months
      did not have any evidence of locoregional recurrence in the median time of 17
      months. CONCLUSION: Fused images were found to be useful to delineate GTV
      required in IMRT planning. PET/CT should be considered for both initial staging
      and treatment planning in patients with head-and-neck carcinoma.

PMID- 16618578
TI  - Gene expression profile changes correlating with radioresistance in human cell
      lines.
AB  - PURPOSE: To identify gene expression profiles specific to radioresistance of
      human cells. METHODS AND MATERIALS: Global gene expression profiles of a total of
      15 tumor and normal fibroblast cell lines were analyzed using DNA microarrays and
      statistical clustering methods. Initially, six of the cell lines were categorized
      into radioresistant (RG) or nonradioresistant (NRG) groups according to the
      radiation dose required to reduce their survival to 10% (D10). Genes for which
      expression was specific to each group at 1 or 3 h after irradiation were
      identified using statistical procedures including analysis of variance and a two
      dimensional hierarchical clustering method. The remaining nine cell lines were
      subjected to the k-nearest neighbor pattern classification. RESULTS: The nine
      test cell lines were successfully classified by their D10 value using 46 and 44
      genes for which transcription levels had significantly changed at 1 and 3 h after
      irradiation, respectively. Of these genes, 25 showed altered expression at both
      time points in the NRG or RG, but independently were unable to classify the test
      cell lines. CONCLUSIONS: Radioresistant cell lines analyzed in this study showed
      certain radiation-induced changes in gene expression profiles that are different
      from the profile changes of the more-sensitive cell lines.

PMID- 16618579
TI  - Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and
      potential intrinsic hypoxia markers.
AB  - PURPOSE: To detect and quantify hypoxia in colorectal adenocarcinomas by use of
      pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic
      anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor
      (EGFR), and vascular endothelial growth factor (VEGF) as intrinsic markers of
      hypoxia. METHODS AND MATERIAL: Twenty patients with an adenocarcinoma of the left
      colon and rectum treated by primary surgery were injected with pimonidazole and
      IdUrd. Serial sections of tumor biopsies were single stained for VEGF, EGFR,
      Ki67, and double stained for blood vessels in combination with either
      pimonidazole, IdUrd, or CA IX. Percentage of expression was scored as well as
      colocalization of pimonidazole with CA IX. RESULTS: The median percentage of
      hypoxia, as judged by pimonidazole staining, was 16.7% (range, 0-52.4%). The
      expression of pimonidazole correlated inversely with the total MVD and
      endothelial cord MVD (R = -0.55, p = 0.01; R = -0.47, p = 0.04). Good
      colocalization was found between pimonidazole and CA IX in only 30% of tumors,
      with no correlation overall between pimonidazole and CA IX, VEGF, or EGFR or
      between the different intrinsic markers. Cells around some vessels (0.08-11%)
      were negative for IdUrd but positive for Ki 67, which indicated their lack of
      perfusion at the time of injection. CONCLUSION: Chronic and acute hypoxic regions
      are present in colorectal tumors, as shown by pimonidazole and IdUrd staining.
      Only in a minority of tumors did an association exist between the areas stained
      by pimonidazole and those positive for CA IX. Pimonidazole also did not correlate
      with expression of other putative intrinsic hypoxia markers (VEGF, EGFR).

PMID- 16618580
TI  - Multiple fields may offer better esophagus sparing without increased probability
      of lung toxicity in optimized IMRT of lung tumors.
AB  - PURPOSE: To evaluate whether increasing numbers of intensity-modulated radiation
      therapy (IMRT) fields enhance lung-tumor dose without additional predicted
      toxicity for difficult planning geometries. METHODS AND MATERIALS: Data from 8
      previous three dimensional conformal radiation therapy (3D-CRT) patients with
      tumors located in various regions of each lung, but with planning target volumes
      (PTVs) overlapping part of the esophagus, were used as input. Four optimized
      beamlet IMRT plans (1 plan that used the 3D-CRT beam arrangement and 3 plans with
      3, 5, or 7 axial, but predominantly one-sided, fields) were compared. For IMRT,
      the equivalent uniform dose (EUD) in the whole PTV was optimized simultaneously
      with that in a reduced PTV exclusive of the esophagus. Normal-tissue complication
      probability-based costlets were used for the esophagus, heart, and lung. RESULTS:
      Overall, IMRT plans (optimized by use of EUD to judiciously allow relaxed PTV
      dose homogeneity) result in better minimum PTV isodose surface coverage and
      better average EUD values than does conformal planning; dose generally increases
      with the number of fields. Even 7-field plans do not significantly alter normal
      lung mean-dose values or lung volumes that receive more than 13, 20, or 30 Gy.
      CONCLUSION: Optimized many-field IMRT plans can lead to escalated lung-tumor dose
      in the special case of esophagus overlapping PTV, without unacceptable alteration
      in the dose distribution to normal lung.

PMID- 16618581
TI  - A dosimetric analysis of intensity-modulated radiation therapy (IMRT) as an
      alternative to adjuvant high-dose-rate (HDR) brachytherapy in early endometrial
      cancer patients.
AB  - PURPOSE: To evaluate the role of intensity-modulated radiation treatment (IMRT)
      as an alternative to high-dose-rate (HDR) brachytherapy in the treatment of the
      vagina in postoperative early endometrial cancer patients after surgery. METHODS
      AND MATERIALS: Planning computed tomography (CT) scans of 10 patients previously
      treated with HDR were used in this study. In all cases, a dose of 700
      cGy/fraction was prescribed at a distance of 0.5 cm from the cylinder surface.
      The same CT scans were then used in IMRT planning. In this paradigm, the vaginal
      cylinder represents a component of a hypothetical immobilization system that
      would be indexed to the linac treatment table. RESULTS: Our study showed that
      IMRT provided relatively lower rectal doses than HDR when treatment was
      prescribed at a distance of 0.5 cm away from the cylinder surface. Maximum rectal
      doses were lower with IMRT compared with HDR (average: 89.0% vs. 142.6%,
      respectively, p < 0.05). Moreover, the mean rectal dose was lower in IMRT plans
      compared with HDR plans with treatment prescribed either to the surface (average:
      14.8% vs. 21.4%, respectively, p < 0.05) or to 0.5 cm (average: 19.6% vs. 33.5%,
      respectively, p < 0.05). IMRT plans had planning target volume (PTV) coverage
      comparable with HDR (average PTV minimum for treatment prescribed to 0.5 cm:
      93.9% vs. 92.1%, p = 0.71, respectively) with less inhomogeneity (average PTV
      maximum: 110.8% vs. 381.6%, p < 0.05). CONCLUSION: Our dosimetric analysis
      suggests that when used in conjunction with a suitable immobilization system,
      IMRT may provide an alternative to HDR brachytherapy in women with early
      endometrial cancer after hysterectomy. However, more studies are needed to
      evaluate the clinical merit of the IMRT in these patients.

PMID- 16618582
TI  - A dosimetric analysis of dose escalation using two intensity-modulated radiation
      therapy techniques in locally advanced pancreatic carcinoma.
AB  - PURPOSE: To perform an analysis of three-dimensional conformal radiation therapy
      (3D-CRT), sequential boost intensity-modulated radiation therapy (IMRTs), and
      integrated boost IMRT (IMRTi) for dose escalation in unresectable pancreatic
      carcinoma. METHODS AND MATERIALS: Computed tomography images from 15 patients
      were used. Treatment plans were generated using 3D-CRT, IMRTs, and IMRTi for dose
      levels of 54, 59.4, and 64.8 Gy. Plans were analyzed for target coverage, doses
      to liver, kidneys, small bowel, and spinal cord. RESULTS: Three-dimensional-CRT
      exceeded tolerance to small bowel in 1 of 15 (6.67%) patients at 54 Gy, and 4 of
      15 (26.7%) patients at 59.4 and 64.8 Gy. 3D-CRT exceeded spinal cord tolerance in
      1 of 15 patients (6.67%) at 59.4 Gy and liver constraints in 1 of 15 patients
      (6.67%) at 64.8 Gy; no IMRT plans exceeded tissue tolerance. Both IMRT techniques
      reduced the percentage of total kidney volume receiving 20 Gy (V20), the
      percentage of small bowel receiving 45 Gy (V45), and the percentage of liver
      receiving 35 Gy (V35). IMRTi appeared superior to IMRTs in reducing the total
      kidney V20 (p < 0.0001), right kidney V20 (p < 0.0001), and small bowel V45 (p =
      0.02). CONCLUSIONS: Sequential boost IMRT and IMRTi improved the ability to
      achieve normal tissue dose goals compared with 3D-CRT. IMRTi allowed dose
      escalation to 64.8 Gy with acceptable normal tissue doses and superior dosimetry
      compared with 3D-CRT and IMRTs.

PMID- 16618583
TI  - Evaluation of two tomotherapy-based techniques for the delivery of whole-breast
      intensity-modulated radiation therapy.
AB  - PURPOSE: To evaluate two different techniques for whole-breast treatments
      delivered using the Hi-ART II tomotherapy device. METHODS AND MATERIALS:
      Tomotherapy uses the standard rotational helical delivery. Topotherapy uses a
      stationary gantry while delivering intensity-modulated treatments. CT scans from
      5 breast cancer patients were used. The prescription dose was 50.4 Gy. RESULTS:
      On average, 99% of the target volume received 95% of prescribed dose with either
      technique. If treatment times are restricted to less than 9 min, the average
      percentage ipsilateral lung receiving > or =20 Gy was 22% for tomotherapy vs. 10%
      for topotherapy. The ipsilateral lung receiving > or =50.4 Gy was 4 cc for
      tomotherapy vs. 27 cc for topotherapy. The percentage of left ventricle receiving
      > or =30 Gy was 14% with tomotherapy vs. 4% for topotherapy. The average doses to
      the contralateral breast and lung were 0.6 and 0.8 Gy, respectively, for
      tomotherapy vs. 0.4 and 0.3 Gy for topotherapy. CONCLUSIONS: Tomotherapy provides
      improved target dose homogeneity and conformality over topotherapy. If delivery
      times are restricted, topotherapy reduces the amount of heart and ipsilateral
      lung volumes receiving low doses. For whole-breast treatments, topotherapy is an
      efficient technique that achieves adequate target uniformity while maintaining
      low doses to sensitive structures.

PMID- 16618584
TI  - IMRT boost dose planning on dominant intraprostatic lesions: gold marker-based
      three-dimensional fusion of CT with dynamic contrast-enhanced and 1H
      spectroscopic MRI.
AB  - PURPOSE: To demonstrate the theoretical feasibility of integrating two functional
      prostate magnetic resonance imaging (MRI) techniques (dynamic contrast-enhanced
      MRI [DCE-MRI] and 1H-spectroscopic MRI [MRSI]) into inverse treatment planning
      for definition and potential irradiation of a dominant intraprostatic lesion
      (DIL) as a biologic target volume for high-dose intraprostatic boosting with
      intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: In 5 patients,
      four gold markers were implanted. An endorectal balloon was inserted for both CT
      and MRI. A DIL volume was defined by DCE-MRI and MRSI using different prostate
      cancer-specific physiologic (DCE-MRI) and metabolic (MRSI) parameters. CT-MRI
      registration was performed automatically by matching three-dimensional gold
      marker surface models with the iterative closest point method. DIL-IMRT plans,
      consisting of whole prostate irradiation to 70 Gy and a DIL boost to 90 Gy, and
      standard IMRT plans, in which the whole prostate was irradiated to 78 Gy were
      generated. The tumor control probability and rectal wall normal tissue
      complication probability were calculated and compared between the two IMRT
      approaches. RESULTS: Combined DCE-MRI and MRSI yielded a clearly defined single
      DIL volume (range, 1.1-6.5 cm3) in all patients. In this small, selected patient
      population, no differences in tumor control probability were found. A decrease in
      the rectal wall normal tissue complication probability was observed in favor of
      the DIL-IMRT plan versus the plan with IMRT to 78 Gy. CONCLUSION: Combined DCE
      MRI and MRSI functional image-guided high-dose intraprostatic DIL-IMRT planned as
      a boost to 90 Gy is theoretically feasible. The preliminary results have
      indicated that DIL-IMRT may improve the therapeutic ratio by decreasing the
      normal tissue complication probability with an unchanged tumor control
      probability. A larger patient population, with more variations in the number,
      size, and localization of the DIL, and a feasible mechanism for treatment
      implementation has to be studied to extend these preliminary tumor control and
      toxicity estimates.

PMID- 16618585
TI  - A study of a pretreatment method to predict the number of I-125 seeds required
      for prostate brachytherapy.
AB  - PURPOSE: Prediction of the number of iodine seeds (I-125) required for prostate
      implantation is an important tool to reduce the number of unused seeds for
      brachytherapy. This study was designed to investigate the relationship between
      the number of seeds implanted vs. prostate volume. This can produce a tool to
      accurately estimate the number of seeds required for a given target volume. In
      addition, total cost of treatment, personal radiation risks during storage and
      handling, and errors in accounting for seeds can be reduced. METHODS AND
      MATERIALS: Data from two groups of patients who had I-125 seed prostate implants
      (Oncura/Amersham RAPIDStrand model 6711 I-125) have been separately analyzed: (A)
      The relationship between prostate volume vs. number of seeds implanted was based
      on 401 patients treated between 1999 and 2002 who were implanted with seeds of
      air kerma strength (AKS) of 0.459 microGy h(-1) @ 1 m per seed. (B) The
      relationship between prostate volume vs. total seed AKS was analyzed. This was
      based on 628 patients treated between 1999 and 2002 who were implanted with a
      range of seed strengths from 0.381 to 0.521 U. Both patient groups were
      subdivided into integer prostate volume bins. For each bin, the mean and 95%
      confidence intervals (CI) for the implanted number of seeds or total AKS
      implanted were calculated. The upper 95% CI was used to investigate the
      relationship between the number of seeds implanted and total AKS implanted vs.
      prostate volume. RESULTS: The new method of predicting the number of seeds shows
      valid and accurate results. The required number of seeds can be predicted, which
      helps to reduce the number of leftover seeds to 3% of the total number of seeds
      ordered. CONCLUSION: The number of I-125 seeds or the total activity that is
      required to deliver the prescribed dose for the target volume can be predicted.
      This could reduce the overall treatment cost by accurate seed ordering before
      implantation.

PMID- 16618586
TI  - Induced acute erythema and late pigmentation may not be correlated: in regards to
      Perera et al. (Int J Radiat Oncol Biol Phys 2005;62:1283-1290).

PMID- 16618587
TI  - Practical setup and appropriate parameters are essential for plan comparison: in
      regards to Ringash et al. (Int J Radiat Oncol Biol Phys 2005;63:732-738).

PMID- 16618589
TI  - Nursing education as an intervention to decrease fatigue perception in oncology
      patients.
AB  - People with cancer have identified fatigue as a major obstacle to normal
      functioning and a good quality of life. It is a nearly universal symptom for
      patients undergoing primary antineoplasic therapy or treatment with biologic
      response modifiers (BRM) and is extremely common in patients with persistent or
      advanced disease. The aim of the study was to determine whether nursing education
      decreased the perception of fatigue in patients with colon or gastric cancer. We
      compared the fatigue level between two groups of patients who received the same
      treatment and had the same type of cancer (experimental group and control group).
      We provided an individualised and structured nursing intervention with education
      to the experimental group. We followed up the fatigue level in both groups with
      three different measures on the Functional Assessment of Cancer Therapy Fatigue
      (FACT-F) Scale. After the nursing intervention there was a decrease in the level
      of fatigue in the experimental group, whereas the group of patients that did not
      receive this intervention showed an increase in fatigue level along the
      treatment. The nursing intervention with the individualised education and
      counselling has provided patients with cancer with an effective tool to manage
      fatigue.

PMID- 16618590
TI  - Bringing immunology to the classroom.

PMID- 16618591
TI  - Tuberculosis: back on the immunologists' agenda.
AB  - Although tuberculosis research was instrumental in the birth of immunology, the
      two disciplines soon separated. The time is ripe for a reunion. Immunology has
      much to offer for rational intervention measures toward tuberculosis control.

PMID- 16618592
TI  - Multiple paths to multispecificity.
AB  - The limited primary antibody repertoire uses multiple mechanisms to account for
      the large number of potential antigens. In this issue of Immunity, Sethi et al.
      (2006) describe a new means for expanding the antibody repertoire, whereby a
      single antibody isomer binds diverse antigens at different regions of the binding
      site.

PMID- 16618593
TI  - Some nuts are tougher to crack than others.
AB  - In this issue of Immunity, Oestreich et al. (2006) show that, during V(D)J
      recombination, RSSs may have distinct accessibility requirements. Some rely on an
      enhancer-intrinsic, general chromatin opening function, whereas others require
      enhancer-promoter interactions that direct local chromatin remodeling.

PMID- 16618594
TI  - PGRP-LB minds the fort.
AB  - Peptidoglycan recognition proteins (PGRPs) are a class of molecules that play a
      critical role in Drosophila immunity. In this issue of Immunity, Zaidman-Remy et
      al. (2006) show that PGRP-LB controls systemic immune responses as well as
      homeostasis at the barrier surfaces.

PMID- 16618595
TI  - Alveolar macrophage in the driver's seat.
AB  - Although alveolar macrophages are normally quiescent to prevent damaging the
      alveoli, in this issue of Immunity, Takabayshi et al. (2006) demonstrate that
      alveolar macrophages can self-regulate their function on demand to mount an
      appropriate immune response.

PMID- 16618596
TI  - T helper cell differentiation: regulation by cis elements and epigenetics.
AB  - Cytokine loci undergo changes in chromatin structure when naive CD4(+) T cells
      differentiate into Th1 or Th2 cells and have also been examined for regulatory
      sequences underlying such changes and their functional correlates. Studies have
      shown that distal regulatory elements control the Ifng and Th2 cytokine loci and
      are primary targets for tissue-specific transcription factors, serving as centers
      for epigenetic changes that mark heritable traits in effector cells. Reports of
      intra- and, remarkably, interchromosomal interactions between these regulatory
      elements shed light on the mechanisms by which they regulate gene expression,
      revealing an extraordinary new picture that conceptually extends our views on how
      genes are regulated from two to three dimensions. Here, we summarize these recent
      findings on the role of regulatory elements and their mechanisms of action, which
      are of broad significance for gene regulation, not only of the immune system but
      also of many, if not all, coregulated genes.

PMID- 16618597
TI  - Regulation of TCRbeta gene assembly by a promoter/enhancer holocomplex.
AB  - Antigen receptor gene assembly is governed by transcriptional promoters and
      enhancers that communicate over large distances and modulate chromatin
      accessibility to V(D)J recombinase. The precise role of these cis-acting elements
      in opening chromatin at recombinase targets and the mechanisms underlying their
      crosstalk remain unclear. We show that the TCRbeta enhancer (Ebeta) directs long
      range chromatin opening over both DbetaJbeta clusters. Strikingly, chromatin
      associated with the Dbeta1 gene segment is refractory to Ebeta-mediated opening.
      Accessibility at Dbeta1 is accompanied by the formation of a stable holocomplex
      between a Dbeta-proximal promoter and Ebeta. These findings indicate a stepwise
      process for Dbeta --> Jbeta recombination that relies on distinct aspects of
      Ebeta activity: an intrinsic function that directs general chromatin opening and
      a cooperative function that facilitates the assembly of a promoter/enhancer
      holocomplex, unmasks the Dbeta1 gene segment, and triggers TCRbeta gene assembly.

PMID- 16618598
TI  - The mismatch repair protein Msh6 influences the in vivo AID targeting to the Ig
      locus.
AB  - Somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by
      activation-induced cytidine deaminase (AID), which preferentially deaminates
      deoxycytidines at WRC (W = A/T, R = A/G) motifs in vitro. The mechanisms
      responsible for targeting AID and for organizing the queue of enzymes involved in
      vivo have been elusive. Here, we examined point mutant knockin Msh6 mice
      (Msh6(TD/TD)), which lack the second phase of SHM but retain all the proteins
      involved, and found that AID was frequently targeted to non-WRC motifs.
      Unexpectedly, by comparing SHM and CSR in wild-type, Msh6(TD/TD), and age-matched
      Msh6(-/-) mice, we discovered that the presence of Msh6 protein influenced the
      AID targeting in phase one of SHM and mediated the proper targeting of
      recombination sites in CSR in vivo. Our data suggest that Msh6 plays a
      scaffolding role in the first phase of SHM, in addition to its enzymatic role in
      the second phase of SHM.

PMID- 16618599
TI  - A recombination silencer that specifies heterochromatin positioning and ikaros
      association in the immunoglobulin kappa locus.
AB  - Allelic exclusion ensures that individual B lymphocytes produce only one kind of
      antibody molecule. Previous studies have shown that allelic exclusion of the
      mouse Igkappa locus occurs by the combination of monoallelic silencing and a low
      level of monoallelic activation for rearrangement combined with a negative
      feedback loop blocking additional functional rearrangements. Using yeast
      artificial chromosome-based single-copy isotransgenic mice, we have identified a
      cis-acting element that negatively regulates rearrangement in this locus,
      specifically in B cells. The element, termed Sis, resides in the V-J intervening
      sequence. Sis specifies the targeting of Igkappa transgenes in pre-B and B cells
      to centromeric heterochromatin and associates with Ikaros, a repressor protein
      that also colocalizes with centromeric heterochromatin. Significantly, these are
      hallmarks of silenced endogenous germline Igkappa genes in B cells. These results
      lead us to propose that Sis participates in the monoallelic silencing aspect of
      allelic exclusion regulation.

PMID- 16618600
TI  - Rap1 signal controls B cell receptor repertoire and generation of self-reactive
      B1a cells.
AB  - We previously reported that the mice deficient for SPA-1, a Rap1 GTPase
      activating protein, developed hematopoietic stem cell disorders. Here, we
      demonstrate that SPA-1(-/-) mice show an age-dependent increase in B220(high) B1a
      cells producing anti-dsDNA antibody and lupus-like nephritis. SPA-1(-/-)
      peritoneal B1 cells revealed the altered Vkappa gene repertoire, including skewed
      Vkappa4 usage and the significant Igkappa/Iglambda isotype inclusion indicative
      of extensive receptor editing. Rap1GTP induced OcaB gene activation via p38MAPK
      dependent Creb phosphorylation, and consistently, SPA-1(-/-) immature BM B cells
      showing high Rap1GTP exhibited the augmented expression of OcaB and Vkappa4
      genes. SPA-1(-/-) BM cells could transfer the autoimmunity in association with
      the generation of peritoneal B220(high) B1a cells in Rag-2(-/-) recipients.
      Finally, a portion of SPA-1(-/-) mice developed B1 cell leukemia with hemolytic
      autoantibody. Present results suggest that the regulated Rap1 signal in the
      immature B cells plays a role in modifying the B cell receptor repertoire and in
      maintaining the self-tolerance.

PMID- 16618601
TI  - Differential epitope positioning within the germline antibody paratope enhances
      promiscuity in the primary immune response.
AB  - Correlation between the promiscuity of the primary antibody response and
      conformational flexibility in a germline antibody was addressed by using germline
      antibody 36-65. Crystallographic analyses of the 36-65 Fab with three independent
      dodecapeptides provided mechanistic insights into the generation of antibody
      diversity. While four antigen-free Fab molecules provided a quantitative
      description of the conformational repertoire of the antibody CDRs, three Fab
      molecules bound to structurally diverse peptide epitopes exhibited a common
      paratope conformation. Each peptide revealed spatially different footprints
      within the antigen-combining site. However, a conformation-specific lock
      involving two shared residues, which were also associated with hapten binding,
      was discernible. Unlike the hapten, the peptides interacted with residues that
      undergo somatic mutations, suggesting a possible mechanism for excluding
      "nonspecific" antigens during affinity maturation. The observed multiple binding
      modes of diverse epitopes within a common paratope conformation of a germline
      antibody reveal a simple, yet elegant, mechanism for expanding the primary
      antibody repertoire.

PMID- 16618602
TI  - Residual antigen presentation after influenza virus infection affects CD8 T cell
      activation and migration.
AB  - Activated virus-specific CD8 T cells remain in the lung airways for several
      months after influenza virus infection. We show that maintenance of this cell
      population is dependent upon the route of infection and prolonged presentation of
      viral antigen in the draining lymph nodes (DLN) of the respiratory tract. The
      local effects on T cell migration have been examined. We show retention of virus
      specific CD8 T cells in the mediastinal lymph node (MLN) and continuing
      recruitment of blood-borne migrants into the lung airways during antigen
      presentation. These data show that antigen that is retained after pulmonary
      influenza virus infection controls the migratory pattern and activation state of
      virus-specific CD8 T cells near the site of virus amplification.

PMID- 16618603
TI  - Serine protease inhibitor 6 protects cytotoxic T cells from self-inflicted injury
      by ensuring the integrity of cytotoxic granules.
AB  - How cytotoxic T lymphocytes (CTLs) kill intracellular pathogens without killing
      themselves has been a recurring question ever since their discovery. By using
      mice deficient in Serine Protease Inhibitor 6 (Spi6), we show that by inhibiting
      granzyme B (GrB), Spi6 protects CTLs from self-inflicted injury. Infection with
      either Lymphocytic Choriomeningitis virus (LCMV) or Listeria monocytogenes (LM)
      revealed increased apoptosis and diminished survival of Spi6 knockout (KO) CTLs,
      which was cell autonomous and could be corrected by GrB deficiency. Spi6 KO mice
      in turn were impaired in their ability to clear LCMV infection. Spi6 KO CTLs
      revealed a breakdown in the integrity of cytotoxic granules, increased
      cytoplasmic GrB, and ensuing apoptosis. We conclude that Spi6 protects CTLs from
      suicide caused by GrB-mediated breakdown of cytotoxic granules.

PMID- 16618604
TI  - The Drosophila amidase PGRP-LB modulates the immune response to bacterial
      infection.
AB  - The Drosophila host defense against gram-negative bacteria is mediated by the Imd
      pathway upon sensing of peptidoglycan by the peptidoglycan recognition protein
      (PGRP)-LC. Here we report a functional analysis of PGRP-LB, a catalytic member of
      the PGRP family. We show that PGRP-LB is a secreted protein regulated by the Imd
      pathway. Biochemical studies demonstrate that PGRP-LB is an amidase that
      specifically degrades gram-negative bacteria peptidoglycan. In agreement with its
      amidase activity, PGRP-LB downregulates the Imd pathway. Hence, activation of
      PGRP-LB by the Imd pathway provides a negative feedback regulation to tightly
      adjust immune activation to infection. Our study also reveals that PGRP-LB
      controls the immune reactivity of flies to the presence of ingested bacteria in
      the gut. Our work highlights the key role of PGRPs that encode both sensors and
      scavengers of peptidoglycan, which modulate the level of the host immune response
      to the presence of infectious microorganisms.

PMID- 16618605
TI  - Induction of a homeostatic circuit in lung tissue by microbial compounds.
AB  - TGFbeta presented and activated by integrin alphavbeta6 expressed on alveolar
      epithelial cells (AEC) continuously inhibits the functionality of alveolar
      macrophages (AM). Despite this inhibition, AM retain their ability to respond to
      inhaled microorganisms. Herein we describe a homeostatic circuit through which
      the effects of microbial products on macrophages transiently circumvent this
      inhibition by repressing alphavbeta6 expression on AEC. Subsequent production of
      matrix metalloproteinases by activated AM activates latent TGFbeta, reinduces
      alphavbeta6 expression, and thereby reinstates tonic inhibition of AM function.
      Our results reveal how AM can be activated while minimizing their potential to
      inflict collateral damage to the adjacent lung tissue and indicate that tissue
      specific microenvironmental factors shape organ-specific defense strategies
      against microbial invasion.

PMID- 16618606
TI  - Late-onset and rare far-advanced pulmonary involvement in patients with
      sarcoidosis in Taiwan.
AB  - BACKGROUND: Sarcoidosis is still considered a rare multisystem disorder in
      Taiwan, and data on the disease course and outcome are limited. We analyzed the
      clinical manifestations, disease course and complications in Taiwanese patients
      with sarcoidosis. METHODS: A retrospective cohort design was used. Fifty-six
      patients with sarcoidosis diagnosed between 1985 and 2004 were included. Their
      clinical features, laboratory findings at initial presentation, disease course,
      and complications were analyzed. RESULTS: Forty-three patients (76.8%) were
      female. The mean age at symptom onset was 47 years. The most common clinical
      symptoms were pulmonary (82.1%), cutaneous (23.2%), ophthalmic (19.6%), and
      articular (17.8%). Only two patients presented with Lofgren's syndrome. There was
      a seasonal variation in disease onset, with higher incidence in winter and early
      spring. No advanced pulmonary involvement was noted. Elevated levels of serum
      angiotensin converting enzyme (sACE) were found in 72.5% (29/40) of patients with
      active sarcoidosis, and significantly higher levels of sACE were found in
      patients with lung involvement (27.98+/-1.71 IU/L vs. 18.2+/-2.76 IU/L; p<0.01).
      In 50% (20/40) of patients, sACE levels declined significantly in parallel with
      clinical remission (24.75+/-1.53 IU/L vs. 16.33+/-1.21 IU/L; p<0.05). Spontaneous
      complete remission was found in 20.7% of patients, whereas 39.6% of patients with
      multiple extrapulmonary involvement responded poorly to intensive corticosteroids
      plus various immunosuppressants. CONCLUSION: In this series, the mean age of
      disease onset was in middle age (mean, 47 years old), there was a low incidence
      of Lofgren's syndrome (3.6%), and no patients had advanced pulmonary syndrome.
      The results of this study also suggest that sACE might be a marker of pulmonary
      involvement that is also useful in monitoring disease activity.

PMID- 16618607
TI  - Differences in the prescription patterns of anti-asthmatic medications for
      children by pediatricians, family physicians and physicians of other specialties.
AB  - BACKGROUND: Prescription patterns of anti-asthma medications in children vary
      among doctors in different disciplines and settings, and may reflect differences
      in treatment outcome. The purpose of this study was to analyze the prescribing
      patterns of anti-asthma drugs by pediatricians, family physicians and other
      practitioners. METHODS: Data for a total of 225,537 anti-asthma prescriptions
      were collected from the National Health Insurance Research Database for the
      period from January 1, 2002 to March 31, 2002. These medications included inhaled
      and oral adrenergics, inhaled and oral corticosteroids, xanthine derivatives, and
      leukotriene receptor antagonists prescribed by general pediatricians, family
      physicians and physicians in other disciplines. RESULTS: Oral beta2-agonist was
      the most commonly prescribed drug used as monotherapy, with prescription rates of
      70.4%, 46.9% and 58.0% by pediatricians, family physicians and other physicians,
      respectively. A xanthine derivative was the next most commonly prescribed
      monotherapy. Oral corticosteroid combined with oral beta2-agonist, followed by
      oral beta2-agonist combined with a xanthine derivative were the two most commonly
      prescribed dual-agent combined therapies by all three physician categories. The
      prescription rate for inhaled corticosteroid monotherapy was 7.8% by
      pediatricians, 5.6% by family physicians, and 8.0% by other physicians. The
      prescription rate for inhaled adrenergic was the highest in family physicians
      (14.9%), followed by the other physicians (7.2%), and was lowest in pediatricians
      (3.1%). CONCLUSION: Pediatricians and family physicians appeared to share similar
      opinions on the medical management of children with asthma in that both most
      commonly prescribed oral beta2-agonists and xanthine derivatives, either alone or
      in combination. Family physicians were least likely to prescribe an inhaled
      corticosteroid and most likely to prescribe an inhaled adrenergic agent.

PMID- 16618608
TI  - Persistent fifth aortic arch associated with 22q11.2 deletion syndrome.
AB  - BACKGROUND: Chromosome 22q11.2 deletion is frequently associated with conotruncal
      malformations and aortic arch anomalies. This study investigated the association
      of chromosome 22q11.2 deletion with clinical manifestations in four pediatric
      patients with persistent fifth aortic arch. METHODS: Four patients with
      persistent fifth aortic arch treated between July 1997 and June 2004 were
      included in this retrospective study. There were two girls and two boys, aged 2
      days to 11.3 years, with persistent fifth aortic arch and cardiac conotruncal
      malformations. Chart recordings, plain chest films, two-dimensional and Doppler
      echocardiograms, cardiac catheterization with angiograms, surgical findings, and
      cytogenetic study were analyzed. RESULTS: Clinically, all four patients had the
      cardinal phenotypic features of 22q11.2 deletion syndrome, including
      cardiovascular malformations (conotruncal malformations and aortic arch
      anomalies), abnormal facies, thymic hypoplasia, canopy anomaly of the palate
      (high-arched palate, rather than cleft palate), and hypocalcemia (or
      hypoparathyroidism). All four patients were confirmed to have chromosome 22q11.2
      deletion. CONCLUSION: Congenital conotruncal malformations, including tetralogy
      of Fallot with pulmonary atresia or stenosis, and aortic arch anomalies including
      a persistent fifth aortic arch or a right aortic arch, should lead to suspicion
      of chromosome 22q11.2 deletion when manifested together with any one of the other
      four cardinal phenotypic features.

PMID- 16618609
TI  - Detection of mycobacteria in Crohn's disease by a broad spectrum polymerase chain
      reaction.
AB  - BACKGROUND: The role of mycobacterial infection, particularly related to
      Mycobacterium avium subsp paratuberculosis (Map), in Crohn's disease has long
      been debated. We developed primer pairs capable of detecting a broad spectrum of
      mycobacterium and employed them to investigate surgical specimens from patients
      with Crohn's disease. METHODS: Pan mycobacterium primers of the 65-kDa heat shock
      protein gene (Hsp65) were used in a polymerase chain reaction (PCR) to examine 12
      surgically-resected, formalin-fixed, paraffin-embedded specimens from 11 patients
      with Crohn's disease. The DNA sequences of amplicons were aligned with those in
      GenBank. RESULTS: Mycobacterial DNA was found in specimens from three of 11
      patients. M. mucogenicum was identified in a specimen from one patient and M.
      tuberculosis in two, but Map was not identified in any. CONCLUSION: Hsp65-based
      PCR can be employed to search for occult mycobacterial infection of the
      gastrointestinal tract in patients with a diagnosis or suspicion of Crohn's
      disease. This approach may have a therapeutic implication.

PMID- 16618610
TI  - Development and psychometric properties of the dialysis module of the WHOQOL-BREF
      Taiwan version.
AB  - BACKGROUND: Quality of life (QOL) is now considered to be an important part of
      the assessment of dialysis patients. The aim of this study was to develop and
      assess the reliability, validity and sensitivity of the dialysis module of the
      World Health Organization Quality of Life - Brief (WHOQOL-BREF) Taiwan version
      [WHOQOL-BREF(TW)] in patients undergoing regular hemodialysis (HD). METHODS: QOL
      survey was administered to 283 regular HD patients in metropolitan Taipei. The
      instruments used included: (1) the proposed module - composed of the core part,
      the WHOQOL-BREF(TW), and the six specific items; (2) the symptom/problem (S/P)
      scale - composed of 12 items specific for dialysis patients; (3) the utility
      measure, which was performed with standard gamble (SG) methods; and (4) the
      rating scale (RS). RESULTS: Based on the six criteria of validity, reliability
      and variance of the items, four HD-specific items were selected. Reliability
      study showed that Cronbach's alphas, composite reliability, and test-retest
      reliability (intraclass correlation at an average retest interval of 4-8 weeks)
      of the four domains of physical, psychological, social relationship and
      environment, ranged from 0.74-0.82, 0.79-0.84 and 0.61-0.79, respectively.
      Validity study showed that all the correlations between an item and its
      corresponding domain were highly significant (r>0.4, p<0.01) and larger than the
      correlations between the item and other domains. SG and psychometric measures
      showed relatively low correlations (0.12-0.26). The module showed the same
      construct as the WHOQOL-BREF(TW) under confirmatory factor analysis, whereas the
      exploratory factor analysis showed mild variation. Convergent and discriminant
      validity were good. Global QOL, physical, psychological and environment domains
      had some sensitivity to differentiate the severity of the condition of patients
      receiving HD. Clinical validity was demonstrated in global QOL, physical and
      psychological domains to have significant correlations with S/P scores.
      CONCLUSION: Besides broader coverage than the core WHOQOL-BREF(TW), the dialysis
      module of the WHOQOL-BREF(TW) is a valid, reliable and sensitive QOL instrument
      for the assessment of HD patients in Taiwan.

PMID- 16618611
TI  - Predicting 3-month mortality among patients hospitalized for first-ever acute
      ischemic stroke.
AB  - BACKGROUND: The clinical course of patients with acute ischemic stroke tends to
      be unstable. Understanding the factors contributing to the progression of stroke
      is important for the appropriate management of patients. This study investigated
      the factors related to 3-month mortality at admission in patients with first-ever
      acute ischemic stroke. METHODS: Patients with first-ever acute ischemic stroke
      consecutively admitted to a medical center in Taiwan within 48 hours after stroke
      onset were prospectively followed-up for 3 months. All deaths during this 3-month
      post-stroke period were analyzed. We evaluated only those characteristics that
      could be assessed at admission. Multivariate logistic regression analysis was
      used to identify the main predictors of 3-month stroke-related mortality.
      RESULTS: In the 360 enrolled patients, the inhospital mortality rate was 7.8% (28
      deaths), and the 3-month mortality rate was 9.7% (35 deaths). Twenty-seven deaths
      (77%) were stroke-related. Risk factors for mortality at 3 months included sex
      (odds ratio [OR], 3.18; 95% confidence interval [CI], 1.08-9.41; p=0.036),
      National Institutes of Health Stroke Scale (NIHSS) at admission (per unit
      increase: OR, 1.17; 95% CI, 1.12-1.22; p<0.001), history of cardiac disease (OR,
      2.73; 95% CI, 1.04-7.16; p=0.042), and posterior circulation stroke (OR, 5.25;
      95% CI, 1.92-14.36; p=0.001). CONCLUSION: This study of hospital-based data on
      patients with first-ever acute ischemic stroke in Taiwan found that initial
      NIHSS, posterior circulation stroke and history of cardiac disease were risk
      factors for 3-month mortality.

PMID- 16618612
TI  - Morphometric analysis of mandibular growth in skeletal Class III malocclusion.
AB  - BACKGROUND: The craniofacial growth patterns of untreated individuals with
      skeletal Class III malocclusion have rarely been systemically investigated. This
      study used morphometric techniques to investigate the growth characteristics of
      the mandible in individuals with skeletal Class III malocclusion. METHODS:
      Lateral cephalometric head films of 294 individuals with untreated skeletal Class
      III malocclusion (134 males, 160 females) were selected and divided into five
      triennial age groups (T1-T5) and by gender to identify the morphologic
      characteristics and sexual dimorphism in changes of mandibular growth.
      Procrustes, thin-plate spline, and finite element analyses were performed for
      localization of differences in shape and size changes. Maximum and minimum
      principal axes were drawn to express the directions of shape changes. RESULTS:
      From T1 (age 6-8 years) to T4 (age 15-17 years), the distribution of localized
      size and shape changes of the mandible was very similar between the two genders.
      From T1 to T2 (age 9-11 years), significant lengthening of the condylar region
      was noted (23.4-39.7%). From T2 to T3 (age 12-14 years), the greatest size and
      shape change occurred at the condylar head (27.4-34.9%). From T3 to T4, the
      greatest size and shape changes occurred in the symphyseal region (23.6-42.1%).
      From T4 to T5 (age>or=18 years), significant sexual dimorphism was found in the
      distribution and amount of localized size and shape changes. Females displayed
      little growth increments during T4. Despite differences in the remodeling
      process, the whole mandibular configurations of both genders exhibited similarly
      significant upward and forward deformation from T4 to T5. CONCLUSION: We conclude
      that thin-plate spline analysis and the finite element morphometric method are
      efficient for the localization and quantification of size and shape changes that
      occur during mandibular growth. Plots of maximum and minimum principal directions
      can provide useful information about the trends of growth changes.

PMID- 16618613
TI  - Correction of tetralogy of fallot with absent pulmonary valve syndrome in a young
      infant using a bicuspid equine pericardial tube.
AB  - Absent pulmonary valve syndrome (APVS) is an uncommon variant of tetralogy of
      Fallot (TOF), which manifests morphologically as vestigial pulmonary valve cusps
      at the right ventricle-pulmonary trunk junction. The aneurysmally dilated
      pulmonary arteries may compress the tracheobronchial tree and cause severe
      respiratory distress in the neonatal or infant stage. Early surgical correction
      in these patients is necessary despite the high operative mortality rate. A 1-day
      old male neonate suffered from progressive shortness of breath after birth.
      Echocardiography confirmed the diagnosis of TOF with APVS. The marked dilatation
      of pulmonary arteries resulted in airway compression in addition to heart
      failure. Total surgical correction was performed at 40 days of age, using a
      homemade bicuspid equine pericardial tube for right ventricular outflow
      reconstruction. The short-term follow-up echocardiogram demonstrated good
      motility of the pericardial leaflet. However, patients receiving this type of
      valved conduit require meticulous long-term follow-up.

PMID- 16618614
TI  - Recurrent corneal perforation and acute calcareous corneal degeneration in
      chronic graft-versus-host disease.
AB  - Keratoconjunctivitis sicca (KCS) is a common complication of graft-versus-host
      disease (GVHD), and may lead to corneal epithelial defect and melting. In
      contrast, recurrent corneal calcareous degeneration and perforation is rare. A 46
      year-old woman developed chronic GVHD after bone marrow transplantation for
      aplastic anemia. Severe KCS with corneal melting and calcium deposits were noted
      in the left eye. Penetrating keratoplasty was performed because of corneal
      perforation, but poor re-epithelialization and calcium deposition recurred.
      Lamellar keratectomy and amniotic membrane transplantation (AMT) were performed,
      but acute calcareous degeneration developed with subsequent recurrence of corneal
      perforation. After regraft, AMT and tarsorrhaphy, the corneal graft remained
      clear for 3 months. However, breakdown of the corneal epithelium occurred 3 weeks
      after spontaneous separation of tarsorrhaphy. Six months later, corneal
      perforation recurred again along with exacerbation of GVHD. Regraft was
      performed, but the patient refused tarsorrhaphy and AMT. Poor re
      epithelialization persisted after regraft. Corneal melting with impending corneal
      perforation ensued. Further corneal surgery was refused and the patient chose to
      undergo evisceration. This case demonstrates that the ocular complications of
      GVHD may be severe enough to lead to corneal perforation and calcareous
      degeneration that is recalcitrant to medical and surgical treatment.

PMID- 16618615
TI  - Unusual visualization of an adrenal carcinoma on NP-59 scintiscan.
AB  - [Iodine-131]6-beta-iodomethylnorcholesterol (NP-59) visualization of
      adrenocortical carcinoma is unusual. We describe a 17-year-old female with
      virilization and elevated plasma testosterone, dehydroepiandrosterone sulfate
      (DHEAS) and aldosterone. Magnetic resonance imaging disclosed a 9-cm right
      adrenal mass. NP-59 adrenal scanning displayed unilateral uptake of tracer and no
      visualization of the contralateral adrenal gland. Exploratory laparotomy revealed
      adrenocortical carcinoma. Subsequent immunohistochemical studies confirmed that
      the tumor was capable of producing a mixture of steroids, including testosterone,
      DHEAS and aldosterone. Visualization of an adrenal tumor on NP-59 scintiscan is
      an unusual finding, which cannot exclude the possibility of malignancy.

PMID- 16618616
TI  - Hemothorax due to metastatic hepatocellular carcinoma presenting with massive
      hemoptysis.
AB  - Hemoperitoneum caused by ruptured hepatocellular carcinoma (HCC) is not uncommon
      in patients with HCC. Hemothorax due to rupture of metastatic HCC, however, is a
      very rare complication with high mortality because of uncontrollable hemorrhage.
      We describe a 42-year-old male HCC patient with chest wall metastasis complicated
      by hemothorax with an unusual presentation of massive hemoptysis. He received
      tube thoracotomy immediately and emergency surgery because of persistent
      bleeding. Hemostasis was achieved transiently. Despite intensive care, he died of
      multiple organ failure on the 6th postoperative day. We conclude that hemothorax
      due to a ruptured HCC, as in this case, indicates a very poor prognosis despite
      intensive treatment.

PMID- 16618617
TI  - A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with Hirschsprung
      disease.
AB  - Hirschsprung disease (HSCR) is a congenital disorder characterized by an absence
      of ganglion cells in the nerve plexuses of the lower digestive tract. Although
      mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN,
      SIP1) have been identified in affected individuals, it is now clear that RET and
      EDNRB are the primary genes implicated in the etiology of HSCR. All eight genes
      are involved in the early development of the enteric nervous system, and most act
      through two distinct biochemical pathways mediated by RET and EDNRB. Mutations in
      RET and EDNRB account for up to 50% and 5% of HSCR cases in the general
      population, respectively. Interaction between these two signaling pathways could
      modify RET expression and, therefore, HSCR phenotype. Here, we report the case of
      a 1-year-old Taiwanese boy who presented with abdominal distension since birth
      and bilious vomiting after feeding. HSCR (short-segment type) was diagnosed based
      on X-ray, lower gastrointestinal series and biopsy findings. Mutation analysis
      revealed a heterozygous T>C missense mutation in exon 1 of the EDNRB gene, that
      substitutes the highly conserved cysteine-90 residue in the extracellular domain
      of the G protein-coupled receptor with an arginine residue (C90R). No RET gene
      mutation was detected in this patient.

PMID- 16618618
TI  - Jejunojejunal intussusception following jejunostomy.
AB  - Jejunojejunal intussusception is a rare complication of jejunostomy, and its
      preoperative diagnosis and surgical treatment have not been reported. A 78-year
      old man suffered from vomiting off and on after emergency exploratory laparotomy
      with omentoplasty for perforated duodenal ulcer. He also received Witzel
      jejunostomy for early feeding. Ileus developed postoperatively and plain X-ray of
      the abdomen showed distended small bowel loop with scanty colon gas. Small bowel
      series performed with water-soluble contrast medium revealed substantial fluid
      retention in the stomach, duodenum and proximal jejunum. Infusion of contrast
      medium into the feeding tube revealed normal caliber of the distal small bowel.
      Abdominal sonogram revealed target sign as well as the feeding tube in a dilated
      jejunum. Abdominal computed tomography confirmed the sonographic impression of
      jejunojejunal intussusception. Reduction of intussusception was done during
      exploratory laparotomy. The jejunostomy feeding was continued and the
      postoperative course was uneventful.

PMID- 16618619
TI  - Computed tomographic features of circulatory arrest.
AB  - Although computed tomography (CT) is used widely in evaluating injuries from
      various kinds of trauma, the CT features of circulatory events are rarely
      reported. Recognizing these features is crucial to proper emergency management of
      patients when circulatory events occur during CT examination. We report two
      trauma patients who developed circulatory arrest during CT. Both patients had
      similar CT features of contrast distribution over the dependent portion of the
      right-sided venous system, a finding that has been previously reported only in
      patients with cardiac arrest. The quick paddle look feature may be useful to
      identify the condition and initiate proper resuscitation of patients without
      electrocardiographic monitoring in CT rooms.

PMID- 16618621
TI  - Suppressed working memory on the WMS-III as a marker for poor effort.
AB  - The purpose of this study was to examine the clinical utility of memory minus
      Working Memory Index (memory-WMI) discrepancy scores on the WMS-III for detecting
      poor effort in 145 personal injury litigants (19 poor effort, 126 adequate
      effort). On average, participants in the poor effort group performed
      significantly lower on all WMS-III memory indexes and demonstrated larger memory
      WMI discrepancy scores compared to participants in the adequate effort group.
      Discriminant function analyses using memory-WMI discrepancy scores as independent
      variables revealed poor overall classification rates (60.0% to 63.4%). Based on
      the prevalence of unusually suppressed attention-concentration ability relative
      to memory functioning using unidirectional memory-WMI discrepancy scores, high
      specificity and negative predictive power values were found. However, there was
      unacceptably low sensitivity and positive predictive power. These results suggest
      that memory-WMI discrepancy scores on the WMS-III do not provide clinically
      useful information regarding response set and should be used cautiously as an
      indicator of poor effort.

PMID- 16618620
TI  - Neurocognitive functions and quality of life in haematological patients receiving
      haematopoietic stem cell grafts: a one-year follow-up pilot study.
AB  - Longitudinal data of neurocognitive functions and quality of life (QOL) were
      obtained for a cohort of 25 patients followed before transplant and through the
      first year after haematopoietic stem cell transplantation (SCT). A battery of
      neuropsychological tests and two self-report questionnaires were used to assess
      neurocognitive functions, QOL and psychological functioning. In comparison to
      normative data, up to one-fourth of the patients experienced impaired functioning
      on several cognitive domains before SCT. Random regression modelling revealed a
      slight improvement in the mean group scores of memory tasks over time, especially
      for younger patients. Impairment in neurocognitive functions was positively
      related to depression and anger at baseline, and to the emotional functioning
      scale at follow-up. These preliminary results emphasize the significance of a pre
      treatment assessment and the need of a large baseline sample in future
      longitudinal studies to overcome the expected dropout rate of more than 50%.

PMID- 16618622
TI  - Patterns of memory dysfunction in current and 2-year abstinent MDMA users.
AB  - The popular recreational drug MDMA or "ecstasy" is a selective serotonin
      neurotoxin in many species and has been found to be associated with memory
      dysfunction in human beings. Recent studies suggest that this impairment persists
      after cessation of use for periods up to at least one year. However, there is no
      clear indication as yet concerning which stage of memory processing is impaired
      as a result of MDMA use. In the current study, 31 current MDMA users and 30 MDMA
      users who had been abstinent for more than two years were compared with 30
      controls on the WMS-III. The results suggest that MDMA use is associated with
      memory dysfunction and that this dysfunction persists for up to two years after
      cessation of use. Importantly, the findings suggest that this memory dysfunction
      may be due to interference at the encoding stage of memory processing.

PMID- 16618623
TI  - Relationship of indicators of neuropathology, psychopathology, and effort to
      neuropsychological results in patients with epilepsy or psychogenic non-epileptic
      seizures.
AB  - Previous research suggests epilepsy and psychogenic non-epileptic seizure (PNES)
      patients do not show consistent group differences on neuropsychological measures.
      However, both groups of patients show decreased neuropsychological performance
      when compared to a normal population (Cragar, Berry, Fakhoury, Cibula, & Schmitt,
      2002). Swanson, Springer, Benbadis, and Morris (2000) have suggested epilepsy
      patients show decreased neurocognitive functioning due to neuropathology whereas
      PNES patients show decreased neurocognitive functioning due to psychopathology.
      Effort has also been implicated as an important factor in neuropsychological test
      results in general (Green, 2003). The purpose of this study was to investigate
      the relationships of medical history variables (e.g., duration of disorder),
      neuropathology, psychopathology, and effort to neuropsychological findings in
      epilepsy and PNES patients. Neuropsychological functioning was divided into six
      domains: intelligence, memory, language, executive functions, visual-spatial, and
      motor. Results indicated that medical history variables were related to
      intellectual, memory, language, and motor functioning. Psychopathology was
      associated with all cognitive domains except executive functioning. Effort was
      related to intellectual, memory, language, visual-spatial, and motor functioning.
      Neuropathology and diagnosis were related only to memory.

PMID- 16618624
TI  - Comparison of adult age differences in verbal and visuo-spatial memory: the
      importance of 'pure', parallel and validated measures.
AB  - The study compared age-related decrements in verbal and visuo-spatial memory
      across a broad elderly adult age range. Twenty-four young (18-25 years), 24 young
      old (65-74 years), 24 middle-old (75-84 years) and 24 old-old (85-93 years)
      adults completed parallel recall and recognition measures of verbal and visuo
      spatial memory from the Doors and People Test (Baddeley, Emslie & Nimmo-Smith,
      1994). These constituted 'pure' and validated indices of either verbal or visuo
      spatial memory. Verbal and visuo-spatial memory declined similarly with age, with
      a steeper decline in recall than recognition. Unlike recognition memory, recall
      performance also showed a heightened decline after the age of 85. Age-associated
      memory loss in both modalities was largely due to working memory and executive
      function. Processing speed and sensory functioning (vision, hearing) made minor
      contributions to memory performance and age differences in it. Together, these
      findings demonstrate common, rather than differential, age-related effects on
      verbal and visuo-spatial memory. They also emphasize the importance of using
      'pure', parallel and validated measures of verbal and visuo-spatial memory in
      memory ageing research.

PMID- 16618625
TI  - Cognitive functions in carotid artery disease before endarterectomy.
AB  - Restorative effects of carotid endarterectomy (CEA) on cognitive functioning in
      patients with severe atherosclerotic disease presuppose the existence of
      cognitive deficits prior to the intervention. Thorough examination of this
      premise received only minor attention. The present study assessed symptomatic and
      asymptomatic patients with severe unilateral or bilateral stenosis of the carotid
      arteries one day before CEA. Healthy volunteers with similar demographic
      characteristics served as control subjects. Patients overall showed decreased
      functioning on tests of attention, verbal and visual memory, verbal fluency, and
      psychomotor speed and executive functioning, even after correction for the
      effects of mood. Simple motor skills and visuospatial functioning were not
      affected. Patients grouped according to presence and type of previous clinical
      symptoms and severity of contralateral stenosis only slightly differed from each
      other. The findings leave open the potential of improving cognitive function
      after CEA.

PMID- 16618626
TI  - Processing speed: a strong predictor of verbal memory performance in
      schizophrenia.
AB  - The role of slowing of processing speed in verbal memory impairment in patients
      with schizophrenia was investigated. Forty-one patients with schizophrenia and 41
      healthy control subjects were administered a verbal memory task involving free
      recall of three lists of words, which varied in their degree of semantic
      organization. Standard processing speed tests were administered as well.
      Regression analyses were conducted on the number of words recalled in each list.
      A global processing speed measure was a significant predictor of the recall of
      each list in patients. Patients were very significantly impaired in the recall of
      the three lists relative to healthy controls. However, when the processing speed
      measure was entered in the regression, the significance of diagnosis was
      considerably reduced for one of the lists, with no semantic organization, and
      eliminated for the other two lists which contained semantic organization. These
      findings suggest that slowing in processing speed is an important contributor to
      verbal memory impairment in patients with schizophrenia. The possible role of
      various specific slowing functions is discussed.

PMID- 16618627
TI  - Relationship between alcohol use/abuse, HIV infection and neuropsychological
      performance in African American men.
AB  - This study examines the impact of alcohol use and HIV infection on
      neuropsychological performance in a sample of 497 community-resident African
      American men. HIV serostatus and alcohol use (during the past 12 months) exerted
      an interactive effect on psychomotor speed, reaction time, and motor speed, and
      in general, HIV infected heavy drinkers evidenced significantly poorer
      performance than other HIV positive subjects. Main effects for HIV serostatus
      were noted for reaction time, with seronegative men performing better than
      seropositives. This study examines a sample of men who continue to show increases
      in HIV infection, however, sample specific issues such as comorbid substance use,
      past histories of head injury, and lack of data on alcohol abuse and dependence
      require caution in definitively attributing the findings solely to alcohol and
      HIV. However, these findings suggest that relatively recent heavy alcohol use may
      represent a potential risk factor for more rapid or pronounced cognitive decline
      in HIV positive individuals, and that these patterns may be even more pronounced
      in persons with comorbid substance use.

PMID- 16618628
TI  - Global perception of small numerosities (subitizing) in cerebral-palsied
      children.
AB  - The goal of this study was to investigate how global perception of small
      numerosities (subitizing) develops in cerebral-palsied children (CP), as compared
      to control children. Twenty-nine 4- to 8-year-old CP children were compared to
      controls matched on age and sex. Both groups were asked to quantify sets of one
      to six items displayed briefly on a screen (250 ms). The children were also
      assessed on counting and eye-hand coordination. CP children exhibited a lower
      subitizing limit than control children. In CP and control children, the
      subitizing limit increased significantly with age. In CP children, the subitizing
      limit was positively correlated with counting performance, and both were
      positively correlated with eye-hand coordination. In addition, the subitizing
      limit in CP children with no evidence of a right-hemisphere lesion tended to be
      higher than in children with a right or bilateral lesion, suggesting right
      hemisphere involvement in subitizing. These results support the idea that
      subitizing and counting are not independent processes during development, and
      argue in favor of a model of subitizing that relies on a global process.

PMID- 16618630
TI  - Cases with mild cognitive impairment and Alzheimer's disease fail to benefit from
      repeated exposure to episodic memory tests as compared with controls.
AB  - Memory tests may be predictive for cognitive decline. We investigated the
      sensitivity and change in performance over time of the Hopkins Verbal Learning
      Test (HVLT) and the Mini-Mental Status Examination (MMSE) for Mild Cognitive
      Impairment (MCI) and Alzheimer's Disease (AD) when compared to cognitively
      healthy controls. Participants included elderly controls (n = 54), MCI (n = 19)
      and AD cases (n = 28) from OPTIMA. The MMSE and the HVLT (version 1) were
      administered twice to all subjects with an interval of 2-3 years.MCI and AD cases
      had poorer performance than controls on the HVLT and MMSE at both testing
      episodes (p < 0.05). The HVLT profile over time showed a learning effect in the
      control group (P < 0.0001), a trend to decline in the AD group (p = 0.09) and no
      change in the MCI group (P = 0.8). A subgroup of MCI subjects had lower HVLT
      scores at follow-up. The MMSE profile showed no significant change over time for
      all three groups (P > 0.05). The HVLT had better sensitivity and specificity
      compared to the MMSE for detecting MCI and AD. The HVLT is not only valuable for
      cross-sectional designs but has also proved to be valuable in a longitudinal
      design. Cognitively healthy controls showed evidence of learning strategies on
      the HVLT after a 2-3 year interval, with improved scores at the second testing
      episode. By contrast, an MCI group showed no benefits of previous exposure to
      this test. Lack of use of learning strategies on the HVLT may be an important
      marker of the likelihood of cognitive decline to MCI or dementia.

PMID- 16618629
TI  - Components of depression in HIV-1 infection: their differential relationship to
      neurocognitive performance.
AB  - Both depression and neurocognitive compromise are commonly observed among persons
      infected with the Human Immunodeficiency Virus (HIV). To date, the majority of
      studies have failed to find a consistent relationship between mood and cognition
      among HIV-seropositive (HIV+) individuals, suggesting that these constructs are
      independent of one another. However, depression is a multi-dimensional syndrome
      and its measurement often utilizes multi-factorial instruments containing
      cognitive, affective, somatic, and motivational components. The degree to which
      various symptoms or dimensions of depression might be related to
      neuropsychological performance in HIV-1 infection is not typically explored and
      was a main objective of the current study. A sample of 247 HIV+ persons completed
      both a comprehensive neurocognitive battery and the Beck Depression Inventory
      (BDI) as part of a standard clinical evaluation at a major community hospital. To
      examine the dimensionality of the BDI, a principal components analysis was
      conducted which suggested a three-factor solution comprised of factors
      representing Self-Reproach (SR), Mood-Motivation Disturbance (MM), and Somatic
      Disturbance (SOM). The relationship between each of these three factors and
      neurocognitive performance was examined using both regression and analysis of
      variance techniques. These analyses showed the MM factor, more so than either the
      SR or SOM factors, to be associated with several aspects of neurocognitive
      performance, including verbal memory, executive functioning, and motor speed.
      These findings suggest that certain items on depression rating scales may be more
      indicative of central nervous system (CNS) involvement than others. The
      association between disturbance in mood and motivation and neurocognitive
      compromise may suggest that each are sequelae of disease specific mechanisms.

PMID- 16618631
TI  - Conformity to the power PC theory of causal induction depends on the type of
      probe question.
AB  - P. W. Cheng's (1997) power PC theory of causal induction proposes that causal
      estimates are based on the power (P) of a potential cause, where P is the
      contingency between the cause and effect normalized by the base rate of the
      effect. Most previous research using a standard causal probe question has failed
      to support the predictions of the power PC model but recently Buehner, Cheng, and
      Clifford (2003) found that participants responded in terms of causal power when
      probed with a counterfactual test question, which they argued prompted
      participants to consider the base rate of the effect. However, Buehner et al.
      framed their counterfactual question in terms of frequency, a factor that has
      been demonstrated to decrease base rate neglect in judgements under uncertainty.
      In the experiment reported here, we sought to disentangle the influence of
      counterfactual and frequency framing of the probe question to determine which
      factor is responsible for encouraging responses in terms of causal power.

PMID- 16618632
TI  - Limitations on representation-mediated potentiation of flavour or odour
      aversions.
AB  - Odour aversion learning is often potentiated in the presence of flavour stimuli.
      Establishment of an aversion to an odour is greater when an odour + flavour
      compound is paired with illness than when the odour alone is paired with illness.
      Holland (1983) showed that under some circumstances auditory or olfactory stimuli
      previously paired with flavours may also potentiate odour aversion learning. The
      present experiments examined limitations on this representation-mediated
      potentiation of aversion learning. The results indicated that conditioned stimuli
      (CSs) that activate representations of potentiating cues are themselves immune to
      potentiation by other CS-activated representations, but remain susceptible to
      potentiation by their real stimulus associates.

PMID- 16618633
TI  - Why are artificial polymorphous concepts so hard for birds to learn?
AB  - Stimulus sets defined in terms of artificial polymorphous concepts have
      frequently been used in experiments to investigate the mechanisms of
      discrimination of natural concepts, both in humans and in other animals. However,
      such stimulus sets are frequently difficult for either animals or humans to
      discriminate. Properties of artificial polymorphous stimulus sets that might
      explain this difficulty include the complexity of the individual stimuli, the
      unreliable reinforcement of individual positive features, attentional load,
      difficulties in discriminating some stimulus dimensions, memory load, and a lack
      of the correlation between features that characterizes natural concepts. An
      experiment using chickens as subjects and complex artificial visual stimulus sets
      investigated these hypotheses by training the birds in discriminations that were
      not polymorphous but did have some of the properties listed above.
      Discriminations that involved unreliable reinforcement or high attentional load
      were found to approach the difficulty of polymorphous concept discriminations,
      and these two factors together were sufficient to account for the entire
      difficulty. The usual kind of artificial polymorphous concept may not be a good
      model for natural concepts as they are perceived and discriminated by birds. A
      RULEX account of natural concept learning may be preferable.

PMID- 16618634
TI  - Age of acquisition for naming and knowing: a new hypothesis.
AB  - This paper reports an investigation into the age of acquisition of object names
      and object knowledge in a cross-sectional study of 288 children aged between 3
      years 7 months and 11 years 6 months, comprising equal numbers of boys and girls.
      The objects belonged to four categories: animals, fruit and vegetables,
      implements, and vehicles. They were presented in three image types: line
      drawings, black-and-white photographs, and coloured photographs. In the knowledge
      test, five probe questions were asked for each object given the spoken name.
      Results showed that line drawings were more difficult to name than either black
      and-white photographs or coloured photographs, which did not differ. The boys
      significantly out-performed the girls at naming and knowing, both overall and
      specifically for the category of vehicles. Naming and knowledge increased
      steadily with age but while young children below about 6 years 6 months showed an
      advantage to naming, older children showed an advantage to knowing. Similarly,
      age-of-acquisition measures for each item revealed a significant shift in the
      relationship between naming and knowing at around 80 months. We argue that
      differences in learning experience lead younger and older children to associate
      object names with different types of information, and we suggest that this
      difference probably accounts for the age-of-acquisition effects reported in adult
      object naming.

PMID- 16618635
TI  - Incrementality in naming and reading complex numerals: evidence from eyetracking.
AB  - Individuals speak incrementally when they interleave planning and articulation.
      Eyetracking, along with the measurement of speech onset latencies, can be used to
      gain more insight into the degree of incrementality adopted by speakers. In the
      current article, two eyetracking experiments are reported in which pairs of
      complex numerals were named (arabic format, Experiment 1) or read aloud
      (alphabetic format, Experiment 2) as house numbers and as clock times. We
      examined whether the degree of incrementality is differentially influenced by the
      production task (naming vs. reading) and mode (house numbers vs. clock time
      expressions), by comparing gaze durations and speech onset latencies. In both
      tasks and modes, dissociations were obtained between speech onset latencies
      (reflecting articulation) and gaze durations (reflecting planning), indicating
      incrementality. Furthermore, whereas none of the factors that determined gaze
      durations were reflected in the reading and naming latencies for the house
      numbers, the dissociation between gaze durations and response latencies for the
      clock times concerned mainly numeral length in both tasks. These results suggest
      that the degree of incrementality is influenced by the type of utterance (house
      number vs. clock time) rather than by task (reading vs. naming). The results
      highlight the importance of the utterance structure in determining the degree of
      incrementality.

PMID- 16618636
TI  - Familiarity seekers are fast and novelty seekers are slow.
AB  - Christie and Klein (1995) demonstrated that a familiar item (word) rapidly
      attracts attention when presented simultaneously with an unfamiliar item
      (nonword). However, this finding has never been replicated. The current study is
      an attempt at such a replication. Participants were presented a familiar word and
      unfamiliar nonword in the experimental condition. At varying times after stimulus
      onset one of the items moved, and the participant reported the direction of the
      movement. A replication of Christie and Klein would be obtained if performance
      was better for movement discrimination of the familiar item shortly after onset
      but not at later intervals. The original finding was replicated in fast
      participants while slower participants show a different effect. A potential
      individual difference variable is suggested to explain this difference between
      the fast and slow participants.

PMID- 16618637
TI  - Repetition priming of access to biographical information from faces.
AB  - Two experiments examined repetition priming on tasks that require access to
      semantic (or biographical) information from faces. In the second stage of each
      experiment, participants made either a nationality or an occupation decision to
      faces of celebrities, and, in the first stage, they made either the same or a
      different decision to faces (in Experiment 1) or the same or a different decision
      to printed names (in Experiment 2). All combinations of priming and test tasks
      produced clear repetition effects, which occurred irrespective of whether the
      decisions made were positive or negative. Same-domain (face-to-face) repetition
      priming was larger than cross-domain (name-to-face) priming, and priming was
      larger when the two tasks were the same. It is discussed how these findings are
      more readily accommodated by the Burton, Bruce, and Johnston (1990) model of face
      recognition than by episode-based accounts of repetition priming.

PMID- 16618638
TI  - Visual memory for moving scenes.
AB  - In the present study, memory for picture boundaries was measured with scenes that
      simulated self-motion along the depth axis. The results indicated that boundary
      extension (a distortion in memory for picture boundaries) occurred with moving
      scenes in the same manner as that reported previously for static scenes.
      Furthermore, motion affected memory for the boundaries but this effect of motion
      was not consistent with representational momentum of the self (memory being
      further forward in a motion trajectory than actually shown). We also found that
      memory for the final position of the depicted self in a moving scene was
      influenced by properties of the optical expansion pattern. The results are
      consistent with a conceptual framework in which the mechanisms that underlie
      boundary extension and representational momentum (a) process different
      information and (b) both contribute to the integration of successive views of a
      scene while the scene is changing.

PMID- 16618639
TI  - Mental representation in visual/haptic crossmodal memory: evidence from
      interference effects.
AB  - Two experiments used visual-, verbal-, and haptic-interference tasks during
      encoding (Experiment 1) and retrieval (Experiment 2) to examine mental
      representation of familiar and unfamiliar objects in visual/haptic crossmodal
      memory. Three competing theories are discussed, which variously suggest that
      these representations are: (a) visual; (b) dual-code-visual for unfamiliar
      objects but visual and verbal for familiar objects; or (c) amodal. The results
      suggest that representations of unfamiliar objects are primarily visual but that
      crossmodal memory for familiar objects may rely on a network of different
      representations. The pattern of verbal-interference effects suggests that verbal
      strategies facilitate encoding of unfamiliar objects regardless of modality, but
      only haptic recognition regardless of familiarity. The results raise further
      research questions about all three theoretical approaches.

PMID- 16618640
TI  - Intention in motor learning through observation.
AB  - The purpose of this experiment was to assess whether learning an action through
      observation is enhanced by the intention to reproduce the observed behaviour. Two
      groups of participants observed a model practise a timing task and performed a 24
      hour delayed retention test. Participants in the first group of observers were
      explicitly instructed that they would be required to execute the timing task that
      they had observed as accurately as possible during the delayed retention test.
      Observers in the second group were instructed that they would be required to
      describe as accurately as possible the behaviour that they had observed. A
      control group of participants, who did not observe the model, was also
      administered the delayed retention test. The results of the retention test
      indicated that absolute timing (parameterization) was learned by the observers to
      the same extent with or without intention to reproduce the task. Indeed, on the
      retention test absolute timing for the two groups of observers was as effective
      as that for the models. However, observing with an intention to reproduce the
      task was beneficial for learning the movement's relative timing structure.
      Results are discussed with respect to a potential mechanism by which intention
      enhances observation.

PMID- 16618641
TI  - Simon congruency effects based on stimulus and response numerosity.
AB  - Three choice reaction time experiments documented a Simon-type congruence effect
      involving the numbers of stimuli and responses. In Experiment 1 the stimulus
      consisted of one or two high- or low-pitch tones, and participants were required
      to respond with one or two taps of a response key depending on stimulus pitch.
      Responses were faster when the number of tones matched the required number of
      response taps than when these numbers mismatched. Experiment 2 showed that a
      weaker version of this effect can also be obtained using visual stimuli, and
      Experiment 3 showed that the analogous effect can even be obtained, albeit very
      weakly, with bimodal stimuli. There was also evidence that the number of stimuli
      affected the rate of emitting the two-tap response. These results indicate that
      stimulus numerosity is processed automatically to the level at which it can
      affect the selection and possibly the execution of a varying number of responses.

PMID- 16618642
TI  - Dynamic perception in chess.
AB  - The present study examines the dynamic aspects of perceptual processes in expert
      chess players. This topic is approached in terms of the anticipation processes
      carried out by experienced players during the encoding of chess positions. The
      aim of the first experiment, which used a short-term comparison task, was to
      stress the role of anticipation, which allows expert players to focus their
      attention on the area of the studied position where they expect the likely
      standard move to occur. The second experiment used a long-term recognition task.
      The results showed that expert players made many false recognitions on the new
      positions that could be expected from the positions presented in the preliminary
      study phase. Taken together, the results of the two experiments highlight the
      anticipatory component of expert perception.

PMID- 16618643
TI  - The effect of contextual factors on the judgement of informal reasoning
      fallacies.
AB  - Informal reasoning fallacies are arguments that are psychologically persuasive
      but not valid. In order to judge the validity of these arguments one has to be
      sensitive to the context in which they appear. However, there is no empirical
      study that examines students' sensitivity to contextual factors and whether
      contextual factors actually influence their ability to identify informal
      reasoning fallacies. We hypothesized that when explicitly presented with
      different argumentative contexts, students' performance would reflect their
      sensitivity to the contextual nature of informal reasoning fallacies. The two
      experiments that we conducted support this hypothesis and emphasize the mediating
      role of perspective taking in students' ability to identify fallacious arguments.

PMID- 16618644
TI  - Working memory capacity and the construction of spatial mental models in
      comprehension and deductive reasoning.
AB  - We asked 149 high-school students who were pretested for their working memory
      capacity (WMC) to read spatial descriptions relating to five objects and to
      evaluate conclusions asserting an unmentioned relationship between two of the
      objects. Unambiguous descriptions were compatible with a single spatial
      arrangement, whereas ambiguous descriptions permitted two arrangements; a subset
      of the ambiguous descriptions still determined the relation asserted in the
      conclusion, whereas another subset did not. Two groups of participants received
      different instructions: The deduction group should accept conclusions only if
      they followed with logical necessity from the description, whereas the
      comprehension group should accept a conclusion if it agreed with their
      representation of the arrangement. Self-paced reading times increased on
      sentences that introduced an ambiguity, replicating previous findings in
      deductive reasoning experiments. This effect was also found in the comprehension
      group, casting doubt on the interpretation that people consider multiple possible
      arrangements online. Responses to conclusions could be modelled by a multinomial
      processing model with four parameters: the probability of constructing a correct
      mental model, the probability of detecting an ambiguity, and two guessing
      parameters. Participants with high and with low WMC differed mainly in the
      probability of successfully constructing a mental model.

PMID- 16618645
TI  - Primary carcinoid tumor of the middle ear: a potentially metastasizing tumor.
AB  - The concept of a carcinoid tumor in the gastrointestinal tract and lung is well
      established; less often, patients develop carcinoid tumors in the head and neck
      region. One particularly uncommon site of origin of carcinoid tumors in the head
      and neck area is the middle ear. Middle ear carcinoids have previously been
      approached as benign entities, lacking any capacity for metastasizing. A critical
      review of the literature, however, disclosed a small number of cases in which
      middle ear carcinoid tumors have given rise to regional (cervical node)
      metastases. This in turn suggests that, as is the case with pulmonary carcinoid
      tumors, middle ear carcinoids should be thought of as low-grade malignancies
      which, while relatively slow-growing, nevertheless possess a limited capacity for
      spreading to regional lymph nodes. To date, distant metastases have not been
      associated with middle ear carcinoid tumors.

PMID- 16618646
TI  - Response of cochlear blood flow to prostaglandin E1 applied topically to the
      round window.
AB  - CONCLUSIONS: The increase in cochlear blood flow (CBF) after administration of
      prostaglandin E1 (PGE1) to the round window depends on increased blood flow
      through the anterior inferior cerebellar artery (AICA). OBJECTIVES: To evaluate
      the response of CBF to PGE1 applied topically to the round window, and to
      investigate the origin of blood flow changes after this topical application.
      MATERIAL AND METHODS: The response of CBF to topically applied PGE1 was measured
      by placing the tip of a laser Doppler probe on the bony wall of the basal turn of
      the cochlea after the middle ear mucosa over the cochlea had been removed in
      guinea pigs and rats. In rats, the CBF response to PGE1 administration was
      investigated after occlusion of the AICA or stapedial artery. RESULTS: CBF
      increased following PGE1 administration in both guinea pigs and rats. In rats,
      CBF increased from 100% to 132%+/-10% (mean+/-SD) after the topical application
      of 0.5 microl of a 0.014% PGE1 solution. CBF decreased after occlusion of the
      AICA or stapedial artery but did not increase after PGE1 administration during
      occlusion of the AICA. The CBF response to PGE1 administration was similar before
      and after occlusion of the stapedial artery.

PMID- 16618647
TI  - No evidence of hearing loss in pseudohypoaldosteronism type 1 patients.
AB  - CONCLUSIONS: The fact that pseudohypoaldosteronism type 1 (PHA-1) patients with a
      defect in the alpha subunit of epithelial sodium channels (ENaC) in the cochlea
      have normal hearing suggests compensation by alternative sodium transport
      mechanisms. Consequently, hearing loss due to defective cochlear transmembrane
      serine protease TMPRSS3 activity is likely to be related to its effect on
      proneurotrophin cleavage, indicating an action on neurological components of
      hearing. The normal hearing of PHA-1 patients with affected mineralocorticoid
      receptors, together with experimental results in animals, indicates that the
      mineralocorticoid aldosterone is not the most crucial regulator of sodium
      transport in the cochlea. OBJECTIVE: Profound hearing loss has been observed in
      patients with a defect in transmembrane serine protease TMPRSS3, the presumed
      activator of ENaCs. Renal ENaCs and their regulators, such as the
      mineralocorticoid receptors, are present in the cochlear structures involved in
      hearing. The aim of this study was to investigate whether PHA-1 patients with
      defects in these channels or regulators suffer from hearing impairment. MATERIAL
      AND METHODS: Pure-tone audiometry was performed in four cases with PHA-1 due to
      mutations in alphaENaC (n=2) or mineralocorticoid receptor (n=2). RESULTS: All
      examined cases had normal hearing at all tested frequencies.

PMID- 16618648
TI  - Antimicrobial resistance of Haemophilus influenzae isolated from the nasopharynx
      of Japanese children with acute otitis media.
AB  - CONCLUSION: A high prevalence of penicillin-binding protein gene-mutated (PGM)
      strains of Haemophilus influenzae should be taken into account when treating
      otitis media in children. OBJECTIVE: To evaluate the prevalence of beta-lactamase
      non-producing ampicillin-resistant strains of H. influenzae with mutations in the
      ftsI gene encoding penicillin-binding protein 3 (PBP3) among children with otitis
      media. MATERIAL AND METHODS: A total of 644 nasopharyngeal isolates of H.
      influenzae were collected from pediatric acute otitis media patients with or
      without otitis media with effusion at the clinics of the Department of
      Otolaryngology-Head and Neck Surgery, Wakayama Medical University Hospital and 6
      affiliated hospitals in Wakayama Prefecture between January 1999 and December
      2003. MICs to ampicillin (AMP), cefdinir (CFD), cefaclor (CCL), cefpodoxime (CPD)
      and cefcapene (CFPN) were determined by a microbroth dilution method according to
      the recommendations of the National Committee for Clinical Laboratory Standards.
      Types of mutations in the PBP3 gene (ftsI) were evaluated by means of a
      polymerase chain reaction (PCR)-based genotyping method. The beta-lactamase gene
      (bla) was also identified by means of PCR. RESULTS: Beta-lactamase-producing
      (BLP) strains having the bla gene were identified in 16 isolates (2.5%). PGM
      strains were identified in 279 isolates (43.3%). There were 242 PGM1-non-BLP
      strains (37.6%) with mutations in the variable mutated locus of ftsI, 35 PGM2-non
      BLP strains (5.4%) with mutations in the highly mutated locus of ftsI and 2 BLP
      PGM strains (0.3%) with mutations in ftsI that produced beta-lactamase. BLP-non
      PGM strains producing beta-lactamase without mutations in ftsI were identified in
      14 isolates (2.2%). MICs of PGM1-non-BLP strains to AMP were 0.5-2.0 microg/ml.
      The MIC90 of CDN to the PGM1-non-BLP strains was the lowest (0.06 microg/ml). The
      proportion of PGM1-non-BLP strains increased rapidly during 1999-2002 and then
      decreased in 2003. In contrast, the proportion of PGM2-non-BLP strains increased
      in 2003.

PMID- 16618649
TI  - Dynamic pitch rotation affects eye torsion.
AB  - CONCLUSION: Most of the subjects studied had eye torsion responses to pitch,
      although the direction of torsion varied between subjects. Opposite responses may
      be the result of individual variation in anatomical or physiological vector
      orientations of hair cells in the anterior or posterior utricle or in the
      saccule. OBJECTIVE: This study aimed to determine whether systematic changes in
      eye torsion occur when subjects are rotated in forward and backward pitch.
      MATERIALS AND METHODS: Twenty-one normal subjects were seated in a dual axis
      human rotator, positioned so that the interaural axis was aligned with the axis
      of pitch rotation. Fixation LED suppressed vertical or horizontal eye movement.
      Recordings were carried out in darkness apart from the fixation LED, using a
      three-dimensional eye tracker based on CMOS image sensors. Subjects were twice
      tilted from upright to 90 degrees occiput down, then forward to 45 degrees face
      down. RESULTS: Most subjects had eye torsion changes in response to pitch, with
      mean amplitudes of approximately 2 degrees to 90 degrees backward tilt and 1
      degree to 45 degrees forward tilt. Ten subjects had clockwise torsion to backward
      pitch and counterclockwise to forward pitch; six subjects had the opposite
      responses. Statistical testing of the distributions of the regression slopes
      between these two groups were significant (p<0.001). Five subjects had unclear
      responses.

PMID- 16618650
TI  - Functional outcome of treatment of Meniere's disease with the Meniett pressure
      generator.
AB  - CONCLUSION: Use of the Meniett pressure generator in patients with active
      Meniere's disease (MD) did not affect labyrinthine function. OBJECTIVE: To
      investigate whether application of the Meniett pressure generator in patients
      with active MD significantly affects their labyrinthine function. MATERIAL AND
      METHODS: We measured hearing and labyrinth sensitivity in patients with
      established MD according to American Academy of Otolaryngology-Head and Neck
      Surgery (AAO-HNS) criteria at five different time periods: at baseline; before
      ventilation tube placement; before Meniett treatment; immediately after Meniett
      treatment; and 1 month after cessation of Meniett treatment. RESULTS: A total of
      32 patients met the inclusion criteria and were included in the study. They were
      graded as having definite MD (AAO-HNS stages 2 and 3). No statistically
      significant changes in labyrinthine function were found during Meniett treatment.

PMID- 16618651
TI  - Vestibular rehabilitation and 6-month follow-up using objective and subjective
      measures.
AB  - CONCLUSIONS: Vestibular rehabilitation improves quality of life by reducing the
      degree of handicap, improving the ability to perform everyday tasks and providing
      long-term rehabilitation stability (at 6 months). Recovery of the vestibulo
      ocular reflex and the vestibulo-spinal reflex efficiency was proven by the
      objective results obtained in this study. Vestibular rehabilitation improves both
      subjective and objective parameters, although no significant correlation between
      these two indices was found. OBJECTIVE: To determine the outcome of subjective
      and objective parameters and long-term rehabilitation stability after vestibular
      rehabilitation in 43 patients with vestibular disorders. MATERIAL AND METHODS:
      The subjective tests used were the Medical Outcomes Study 36-item Short Form, the
      Dizziness Handicap Inventory and the Activity-specific Balance Confidence scale.
      The objective tests used were video-oculoscopy, dynamic visual acuity, the
      Equitest and the Dynamic Gait Index. All indices were evaluated before and after
      rehabilitation and at follow-up. RESULTS: All patients showed an improvement in
      quality of life and a reduction in handicap due to dizziness. Improvement in
      objective test results was also seen. These results were stable at follow-up. A
      correlation was found between different subjective measures, but there was no
      correlation between subjective and objective measures.

PMID- 16618652
TI  - Caloric test and simultaneous recording of sympathetic skin response.
AB  - CONCLUSIONS: It was found that there was a close correlation between sympathetic
      skin response (SSR) parameters and nystagmus parameters obtained in caloric
      tests. Further studies are needed to investigate the clinical correlation of
      these findings. OBJECTIVES: To investigate whether the caloric response creates a
      measurable SSR and, if so, to compare the SSR parameters with the nystagmus
      parameters and the feelings of the patient. MATERIAL AND METHODS: Patients
      completed an autonomic symptom questionnaire (ASQ) regarding their past history
      of autonomic symptoms. They used a visual analog scale (VAS) to assess the
      severity of symptoms during simultaneous SSR and caloric tests. Symptoms were
      also noted separately by the investigator. RESULTS: Eighteen patients were
      included in the study (13 females, 5 males). Eight of the patients had central
      and 10 had peripheral vertigo. The mean VAS score was 6.6+/-1.9 and the mean ASQ
      score was 7.2+/-3.6. In terms of the recorded parameters, there were no
      significant differences between patients with central and peripheral vertigo,
      males and females or warm and cold irrigation. The number of SSR waves increased
      significantly when the slow-phase velocity was > 26 degrees/s (p<0.01) and the
      nystagmus latency was < or = 27 s (p<0.05). The VAS score was also correlated
      with the number of SSR waves (p<0.01).

PMID- 16618653
TI  - Experience in the treatment of sudden deafness during pregnancy.
AB  - CONCLUSION: Excluding the possibility of acoustic neuroma, therapeutic benefits
      from dextran 40 can be anticipated in a pregnant woman with sudden deafness,
      leading to significant hearing improvement, without detrimental effect on the
      mother or fetus. OBJECTIVE: The aim of this study was to present our experience
      in the treatment of pregnant women with sudden deafness during the past decade.
      METHODS: From January 1994 to December 2003, 12 pregnant women with sudden
      deafness were consecutively encountered at the authors' clinic. With the
      exception of one patient with acoustic neuroma who underwent craniotomy, six
      patients were treated with dextran 40 only, while the other five patients
      preferred no medication, and served as a control group. Each patient underwent
      audiometry before treatment and at 1 year postpartum. RESULTS: In the dextran
      group, five (83%) of six patients had hearing improvement 1 year postpartum,
      compared with one (20%) of five patients in the control group showing hearing
      improvement; both groups revealed a significant difference. Those receiving
      intravenous dextran treatment had significant hearing improvement at the
      frequencies of 1000, 2000, and 4000 Hz, at 1 year postpartum. In contrast, in
      those who followed a natural course without medication no significant difference
      existed in the mean hearing level of each frequency, at 1 year after delivery.

PMID- 16618654
TI  - Hematoma-like mass of the maxillary sinus.
AB  - CONCLUSIONS: We have reported a non-neoplastic, heterogeneous, hemorrhagic lesion
      of the maxillary sinus characterized by a mixture of dilated vessels, hemorrhage
      and fibrin exudation. This lesion should be distinguished from hemangioma and
      hematoma. We propose the name "hematoma-like mass of the maxillary sinus" for
      this disease, based on its histological characteristics. OBJECTIVE: To describe
      the clinicopathological characteristics of a non-neoplastic, heterogeneous,
      hemorrhagic lesion of the maxillary sinus associated with mucosal swelling and
      bone destruction. MATERIAL AND METHODS: This was a retrospective review of six
      patients who were treated surgically for masses and met the following criteria:
      (i) CT demonstrated an expanding unilateral maxillary lesion, with thinning or
      destruction of the surrounding bony tissue; (ii) MRI demonstrated a heterogeneous
      mass; (iii) macroscopically, a mass with a hemorrhagic and heterogeneous
      appearance was observed; and (iv) histologically, a non-neoplastic tissue with
      mucosal hemorrhage was observed. RESULTS: The clinical features of this disease,
      such as a mass expanding from the maxillary sinus with bone destruction,
      resembled those of maxillary carcinoma. However, CT and MRI provided sufficient
      information to differentiate this condition from malignancy. Resection was
      straightforward due to a firm capsule. Characteristic histological findings were
      a mixture of dilated vessels, hemorrhage and fibrin exudation.

PMID- 16618655
TI  - Particle image velocimetry measurements for the study of nasal airflow.
AB  - CONCLUSIONS: Particle image velocimetry (PIV) permits investigation of the
      distribution and velocity of the airflow in the nasal cavity. During breathing,
      the main laminar flow stream passes through the middle meatus and turbulent flow
      can be detected under physiologic conditions. OBJECTIVES: Physical models or
      casts of the nasal cavity have been utilized in several studies in an effort to
      understand its aerodynamics. PIV is a new technique for measuring the aerodynamic
      properties of tubular structures. In this article we evaluate nasal airflow
      characteristics during physiologic breathing under normal conditions and the
      usefulness of PIV. MATERIAL AND METHODS: A nasal model cast obtained by a
      combination of rapid prototyping and solidification of clear silicone was
      connected to a pump which simulated the physiological pressure in the upper
      airway system. A glycerol-water mixture was used as the flow material. The
      airstream was marked with spherical polyvinyl particles, observed through
      solidified clear silicone and analyzed using PIV. RESULTS: The main flow within
      the cavity, which was mostly laminar, passed through the middle meatus.
      Turbulence was clearly visible in the anteroinferior part of the middle
      turbinate. The flow rate was highest at the middle meatus during inspiration and
      expiration.

PMID- 16618656
TI  - Do topical nasal decongestants affect polyps?
AB  - CONCLUSIONS: The hypothesis that decongestants reduce the size of nasal polyps
      could not be verified. Decongestion is therefore recommended prior to nasal
      endoscopy, especially in polyp diagnosis, as it does not artificially change the
      size of the polyps. OBJECTIVE: The role of nasal decongestants in nasal
      stuffiness is well established and their action is well known. Decongestants are
      also used prior to nasal endoscopy to achieve a better view of the nasal cavity
      in order to diagnose polyps. The question is whether this decongestion
      invalidates the estimation of polyp size in clinical and scientific practice. The
      aim of this study was to evaluate possible effects of topical decongestants on
      polyp extension in patients with nasal polyposis. MATERIAL AND METHODS: The
      effect of the decongestants nafazoline and epinephrine on nasal polyp size was
      assessed by means of a double-blind, placebo-controlled randomized study. A
      sensitive endoscopic scoring system, lateral imaging, was used to assess the size
      and extension of the nasal polyps. RESULTS: No significant effect of decongestion
      on polyp size could be found for either treatment.

PMID- 16618657
TI  - A novel N-chlorotaurine-corticosteroid combination as a preservative-free local
      disinfectant: influence on the ciliary beat frequency in vitro.
AB  - CONCLUSIONS: The combination of N-chlorotaurine (NCT) and a corticosteroid seems
      to be a very promising substance for the local therapy of ENT infections. As it
      can be used without any preservatives, the effect on the ciliary beat frequency
      (CBF) is much less than that of products containing benzalkonium chloride (BAC).
      The in vitro results obtained in this study encourage us to perform clinical
      trials on this novel combination for intranasal application. OBJECTIVE: To
      investigate the influence of a novel mixture of NCT and a corticosteroid
      [fluticasone propionate (FP)] on the CBF of human ciliated cells in vitro.
      MATERIAL AND METHODS: The study was designed as an in vitro study. CBF was
      measured by means of a photometric technique involving the combination of a light
      microscope, a photometer, a photographic multiplier and a computerized analyzing
      unit. RESULTS: The combination of 1% NCT + 0.5 mg/ml FP decreased the CBF to
      42.17% of its original value after 20 min. Treatment with BAC lowered the CBF
      depending on the concentration to 96.61% of its original value with 0.04 mg/ml,
      to 91.90% with 0.1 mg/ml, to 63.46% with 0.2 mg/ml and to 0% with 0.5 mg/ml.
      After rinsing in saline, the CBF of samples treated with 1% NCT + 0.5 mg/ml FP
      recovered to 68.93% of its original value.

PMID- 16618658
TI  - Treatment for extracranial arteriovenous malformations of the head and neck.
AB  - CONCLUSIONS: For extracranial arteriovenous malformations of the head and neck
      (HNAVMs), in which the nidus was accessible via the percutaneous route, ethanol
      sclerotherapy was a feasible and safe first-line treatment, although successful
      outcomes were obtained for only about half of the subjects. For other HNAVMs,
      surgical excision with embolization may be the best choice of treatment.
      OBJECTIVE: To suggest a treatment protocol for patients with HNAVMs by comparing
      the treatment outcomes and complications of ethanol sclerotherapy with those of
      surgical excision combined with embolization. MATERIAL AND METHODS: Twenty
      patients who had been diagnosed with HNAVM and treated between 1995 and 2002 were
      retrospectively reviewed. Ethanol sclerotherapy, surgical excision and
      embolization were used as treatments, either alone or in various combinations.
      The treatment outcomes and complications with the different modalities were
      analyzed. RESULTS: Ethanol sclerotherapy was used for 12 cases, with a success
      rate of 50.0% and a permanent complication rate of 8.3%. Surgical excision
      combined with embolization was used for 13 patients. Although all patients
      achieved successful resolution of their HNAVM after surgical excision, 15.4%
      suffered from permanent complications. In total, 16/20 patients (80.0%)
      eventually achieved a > or = 75% reduction in the size of their lesions.

PMID- 16618659
TI  - p57(kip2) expression is related to carcinogenesis and tumor progression in
      laryngeal tissues.
AB  - CONCLUSIONS: Reduction of p57(kip2) expression is related to carcinogenesis in
      laryngeal mucosa. Assessment of p57(kip2) expression may be a promising candidate
      as a progressive biomarker in laryngeal squamous cell carcinoma (SCC). OBJECTIVE:
      To investigate the expression and significance of p57(kip2) in a
      dysplasia/carcinoma sequence of laryngeal mucosa. MATERIAL AND METHODS: A
      retrospective study was performed involving 10 cases of normal mucosa, 31 of
      laryngeal leukoplakia and 109 of laryngeal SCC. p57(kip2) and p53 protein
      expression was detected in the tissue samples of these patients using
      immunohistochemistry. RESULTS: p57(kip2) expression was decreased in leukoplakia
      with moderate or severe dysplasia, and further decreased in SCC. No significant
      difference was found between normal mucosa and leukoplakia with no or mild
      dysplasia. In patients with laryngeal SCC, advanced tumor size and clinical stage
      and the recurrence of disease were associated with reduced p57(kip2) expression.
      The occurrence of lymph node metastasis was also related to negative expression
      of p57(kip2). The overall 5-year disease-free survival rate of patients with
      laryngeal SCC was significantly higher in the p57(kip2)-positive than in the
      p57(kip2)-negative group.

PMID- 16618660
TI  - Role of margin status in recurrence after CO2 laser endoscopic resection of early
      glottic cancer.
AB  - CONCLUSION: In patients with early glottic squamous cell carcinoma (SCC)
      submitted to CO2 laser endoscopic resection, local disease recurrence was
      significantly correlated with the presence of positive additional surgical
      margins on permanent sections. OBJECTIVES: To evaluate the rate of cancer
      recurrence in patients with early glottic SCC submitted to CO2 laser endoscopic
      resection according to margin status after resection, stage of disease and
      postoperative radiotherapy. The rate of larynx preservation and the length of
      hospital stay were also evaluated. MATERIAL AND METHODS: Forty consecutive
      patients with early glottic cancer were subjected to laser endoscopic resection
      surgery of glottic cancer followed by frozen-section control of margins, with
      intraoperative enlargement of margins when positive. Adjuvant radiation therapy
      or enlargement of previous margins was indicated in the case of positive
      additional surgical margins on permanent section. RESULTS: Local recurrence
      occurred in three patients (7.5%), all with positive additional surgical margins
      on permanent section. Positive additional surgical margins on permanent section
      were related to 37.5% of recurrences and negative additional surgical margins
      with 0% of recurrences (p=0.006). All patients spent at most 1 day at the
      hospital.

PMID- 16618661
TI  - Glutathione S-transferase T1 null polymorphism and the risk for head and neck
      cancer.
AB  - CONCLUSIONS: Inter-regional differences in the distribution of genetic
      polymorphisms in glutathione S-transferases (GSTs) exist, which may have
      significant effect on the outcome of other GST polymorphism studies. The GSTT1
      null genotype appears to be involved in modulation of the risk for head and neck
      squamous cell carcinoma (HNSCC). BACKGROUND: The risk of HNSCC is strongly
      associated with smoking of cigarettes and consumption of alcohol, resulting in a
      load of toxins/carcinogens. Detoxification of such exogenous harmful compounds
      often occurs by phase II enzymes such as GSTs. Proper functioning of these
      enzymes may be deficient due to the presence of particular genetic polymorphisms
      in these GSTs, and this may increase the risk for HNSCC. We compared the GSTT1,
      GSTM1 and GSTP1 genotype frequencies in two groups of healthy blood donors,
      collected from different but adjacent regions in the Netherlands, with those of a
      group of patients with HNSCC. SUBJECTS AND METHODS: The GSTM1,GSTT1 and GSTP1
      genotype frequencies in two Dutch Caucasian control populations (n = 207 and n =
      285) from different but adjacent geographical regions (Maastricht and Nijmegen;
      distance, 125 km) and 185 patients with HNSCC from the Maastricht region were
      determined by PCR-related methods. RESULTS: For the occurrence of the GSTT1 null
      genotype we found a significant difference (p=0.003) between the two control
      groups (20.3% vs 33.0% null genotype in the Nijmegen and Maastricht control
      groups, respectively). Since the HNSCC patients were collected from the
      Maastricht area, comparison with the Maastricht controls reveals a significant
      difference for GSTT1 null rates, which are lower in patients vs controls (OR =
      0.49, CI = 0.32-0.76).

PMID- 16618662
TI  - Resection of cervical vagal schwannoma via a post-auricular approach.
AB  - Cervical vagal schwannomas are extremely rare and gross total resection is the
      standard treatment modality. However, because the conventional cervical approach
      leaves an incision scar in a visible area, other approaches need to be developed
      for young women who want the postoperative scar to be invisible. A 28-year-old
      female underwent complete resection of a 4x4 cm tumor in her right upper neck via
      a post-auricular approach using an inverted V-shaped incision along the post
      auricular sulcus and hairline. The tumor was a schwannoma originating from the
      right cervical vagus nerve. Postoperatively, right vocal cord paralysis developed
      despite careful dissection but completely recovered within 6 months after
      surgery. The patient was satisfied with an invisible external scar which was
      hidden by her auricle and hair. A cervical vagal schwannoma can be successfully
      removed by making an incision in a potentially invisible area.

PMID- 16618663
TI  - Isolated malleus neck fracture.
AB  - Isolated fracture of the malleus seems to be an extremely rare ossicular injury.
      All previously reported cases involved the handle of the malleus. This is the
      first reported case of fracture of the neck of the malleus. The diagnosis can
      easily be missed because the tympanic membrane remains intact. Furthermore, the
      history may not be suggestive. Surgical repair is particularly difficult.

PMID- 16618664
TI  - Bilateral oncocytoma of the parotid gland.
AB  - Oncocytic neoplasms are a group of rare tumours that mostly affect the parotid
      gland (80%), sometimes affect the submandibular gland (9%) and rarely affect the
      intraoral minor salivary glands. The incidence of oncocytic neoplasms represents
      approximately 1% of parotid neoplasms and bilateral presentation is very rare.
      Herein we describe a single case involving bilateral presentation of oncocytoma
      of the parotid glands.

PMID- 16618665
TI  - Giant cell tumour (osteoclastoma) of the zygoma: an extremely unusual neoplasm.
AB  - We report an extremely rare case of a giant cell tumour of the zygomatic bone in
      a 36-year-old female. The tumour was excised with healthy margins. The patient is
      asymptomatic without any evidence of recurrence 14 months postoperatively. To our
      knowledge, this is only the third reported case of this tumour occurring in the
      zygomatic bone in the medical literature.

PMID- 16618666
TI  - Hereditary ectopic salivary gland: survey of three generations.
AB  - An ectopic salivary gland is different from a branchial cleft fistula, which
      generally results from heteroplasia within the remnants of the second branchial
      cleft. Compared to a branchial cleft fistula, surgery for an ectopic salivary
      gland is relatively simple. This study describes five generations of a family
      with typical clinical features of ectopic salivary gland in the neck. This study
      is the first to report the rare familial occurrence of ectopic cervical salivary
      gland and discuss its imaging results, surgical management, and histopathology.

PMID- 16618667
TI  - Candida parotitis with abscess formation.
AB  - This report describes the case of an elderly, diabetic man who developed acute
      suppurative parotitis with abscess formation. The causative agent of parotid
      abscess was Candida albicans, which is an unusual cause of salivary gland
      pathology. The parotid gland is the salivary gland most commonly affected by
      inflammation. Acute parotitis occurs most often in elderly patients who are
      debilitated by systemic disease or are in a state of dehydration following major
      surgical procedures. Despite the high prevalence of oral candida carriage, there
      have been few previous reports of candida sialoadenitis in the literature. This
      is due to the toxicity of saliva to fungi under normal conditions. The diagnosis
      of candidiasis in our patient was made by culturing the purulent discharge from
      Stensen's duct and by culture of the pus obtained at surgical drainage of the
      abscess. After incision and drainage, the patient was treated with intravenous
      and then oral fluconazole for a total of 4 weeks with complete resolution of his
      condition. This case is interesting in light of recent and ongoing investigations
      of salivary proteins as potential new antifungal agents.

PMID- 16618668
TI  - Ancient trans-Atlantic flight explains locust biogeography: molecular
      phylogenetics of Schistocerca.
AB  - The desert locust (Schistocerca gregaria) has been an important agricultural pest
      at least since biblical times. Although the ecology, physiology and behaviour of
      this insect species have been well characterized, its biogeographical origins and
      evolutionary history are more obscure. Schistocerca gregaria occurs throughout
      Africa, the Middle East and Western Asia, but all other species in the genus
      Schistocerca are found in the New World. Because S. gregaria has the capacity for
      extreme long-distance movement associated with swarming behaviour, dispersal may
      have played an important role in determining current distribution patterns. Some
      authors have argued that S. gregaria is the product of an eastward trans-Atlantic
      dispersal from North America to Africa; others consider it more likely that the
      New World taxa are the product of westward dispersal from Africa. Here, we
      present a mitochondrial DNA phylogeny of Schistocerca species that supports the
      monophyly of New World species (including the Galapagos endemic Halmenus)
      relative to S. gregaria. In concert with observed patterns of molecular
      divergence, and in contrast to previous morphological studies, our analysis
      indicates a single trans-Atlantic flight from Africa to South America, followed
      by extensive speciation and ecological divergence in the New World.

PMID- 16618669
TI  - Inference of cowpox virus transmission rates between wild rodent host classes
      using space-time interaction.
AB  - There have been virtually no studies of 'who acquires infection from whom' in
      wildlife populations, but patterns of transmission within and between different
      classes of host are likely to be reflected in the spatiotemporal distribution of
      infection among those host classes. Here, we use a modified form of K-function
      analysis to test for space-time interaction among bank voles and wood mice
      infectious with cowpox virus. There was no evidence for transmission between the
      two host species, supporting previous evidence that they act as separate
      reservoirs for cowpox. Among wood mice, results suggested that transmission took
      place primarily between individuals of the opposite sex, raising the possibility
      that cowpox is sexually transmitted in this species. Results for bank voles
      indicated that infected females might be a more important source of infection to
      either sex than are males. The suggestion of different modes of transmission in
      the two species is itself consistent with the apparent absence of transmission
      between species.

PMID- 16618670
TI  - Dynamics of deletion genotypes in an experimental insect virus population.
AB  - Defective viruses, that are deficient in certain essential genes, are maintained
      in the population by trans-complementation, exploiting the gene products of
      complete genotypes in co-infected cells. This process becomes prevalent only when
      cells are frequently infected by several virus particles, and only then will the
      fitness of defective viruses be subjected to frequency-dependent selection.
      Deletion variants that are not infectious per os are present in a multicapsid
      nucleopolyhedrovirus (SfMNPV, Baculoviridae) that infects the fall army worm,
      Spodoptera frugiperda. These variants enhance the pathogenicity and, therefore,
      the likelihood of transmission of the virus when co-infecting cells with complete
      genotypes, resulting in occlusion bodies (OBs) that may contain both genotypes co
      occluded. Mixtures of complete (B) and defective (C) variants in ratios of 90%
      B+10% C, 50% B+50% C and 10% B+90% C were used to inoculate by injection S.
      frugiperda larvae. Viral OBs extracted from diseased insects were subjected to
      four or five successive rounds of per os infection. Following successive
      passages, genotype frequencies in all three experimental populations converged to
      a single equilibrium frequency comprising approximately 20% of deletion genotype
      C and approximately 80% of complete genotype B. This mirrors the relative
      proportions of deletion (22%) and complete (78%) genotypes observed in the wild
      type SfMNPV population. The pathogenicity of experimental populations at the
      final passage was not significantly different from that of the wild-type isolate.
      In contrast, OBs of all genotype mixtures were significantly more pathogenic than
      OBs of genotype B alone. A population genetics model, in which virus populations
      were assigned linear frequency-dependent transmissibility values, was in
      remarkably close agreement to empirical data. Clearly, non-infectious deletion
      variants can profoundly affect the likelihood of transmission and the genetic
      structure and stability of virus populations.

PMID- 16618671
TI  - Wolbachia infection suppresses both host defence and parasitoid counter-defence.
AB  - Endosymbiotic bacteria in the genus Wolbachia have been linked to several types
      of reproductive parasitism, which enhance their own transmission, while their
      direct effects on the host vary from beneficial to neutral or detrimental. Here,
      we report negative effects of infection on immunity-related traits of Drosophila
      simulans and the parasitoid wasp Leptopilina heterotoma. Infected D. simulans
      showed a reduced ability to encapsulate parasitoid eggs, compared to a
      tetracycline-treated, bacterium-free line. Challenging the two lines with a
      fungal pathogen, Beauveria bassiana, on the other hand, revealed no differences
      in survival. Moreover, elimination of Wolbachia was beneficial for the parasitoid
      wasp, as eggs laid by uninfected females suffered significantly lower
      encapsulation rates. We discuss possible origins of these fitness costs and their
      implications for infection dynamics and the interactions between host species.

PMID- 16618672
TI  - Disease ecology in the Galapagos Hawk (Buteo galapagoensis): host genetic
      diversity, parasite load and natural antibodies.
AB  - An increased susceptibility to disease is one hypothesis explaining how
      inbreeding hastens extinction in island endemics and threatened species.
      Experimental studies show that disease resistance declines as inbreeding
      increases, but data from in situ wildlife systems are scarce. Genetic diversity
      increases with island size across the entire range of an extremely inbred
      Galapagos endemic bird, providing the context for a natural experiment examining
      the effects of inbreeding on disease susceptibility. Extremely inbred populations
      of Galapagos hawks had higher parasite abundances than relatively outbred
      populations. We found a significant island effect on constitutively produced
      natural antibody (NAb) levels and inbred populations generally harboured lower
      average and less variable NAb levels than relatively outbred populations.
      Furthermore, NAb levels explained abundance of amblyceran lice, which encounter
      the host immune system. This is the first study linking inbreeding, innate
      immunity and parasite load in an endemic, in situ wildlife population and
      provides a clear framework for assessment of disease risk in a Galapagos endemic.

PMID- 16618673
TI  - Dynamics of multiple symbiont density regulation during host development: tsetse
      fly and its microbial flora.
AB  - Symbiotic associations often enhance hosts' physiological capabilities, allowing
      them to expand into restricted terrains, thus leading to biological
      diversification. Stable maintenance of partners is essential for the overall
      biological system to succeed. The viviparous tsetse fly (Diptera: Glossinidae)
      offers an exceptional system to examine factors that influence the maintenance of
      multiple symbiotic organisms within a single eukaryotic host. This insect
      harbours three different symbionts representing diverse associations,
      coevolutionary histories and transmission modes. The enterics, obligate mutualist
      Wigglesworthia and beneficial Sodalis, are maternally transmitted to the
      intrauterine larvae, while parasitic Wolbachia infects the developing oocyte. In
      this study, the population dynamics of these three symbionts were examined
      through host development and during potentially disruptive events, including host
      immune challenge, the presence of third parties (such as African trypanosomes)
      and environmental perturbations (such as fluctuating humidity levels). While
      mutualistic partners exhibited well-regulated density profiles over different
      host developmental stages, parasitic Wolbachia infections varied in individual
      hosts. Host immune status and the presence of trypanosome infections did not
      impact the steady-state density levels observed for mutualistic microbes in
      either sex, while these factors resulted in an increase in Wolbachia density in
      males. Interestingly, perturbation of the maternal environment resulted in the
      deposition of progeny harbouring greater overall symbiont loads. The regulation
      of symbiont density, arising from coadaptive processes, may be an important
      mechanism driving inter-specific relations to ensure their competitive survival
      and to promote specialization of beneficial associations.

PMID- 16618674
TI  - No simple answers for ecological immunology: relationships among immune indices
      at the individual level break down at the species level in waterfowl.
AB  - Understanding immune function in the context of other life-history traits is
      crucial to understand the evolution of life histories, at both the individual and
      species levels. As the interest in assessing immune function for these
      comparative purposes grows, an important question remains unanswered: can immune
      function be broadly characterized using one or two simple measures? Often,
      interpretation of individual assays is ambiguous and relationships among
      different measures of immune function remain poorly understood. Thus, we employed
      five protocols to measure 13 variables of immune function in ten species of
      waterfowl (Anseriformes). All assays were based on a single blood sample
      subdivided into leukocyte (blood smear) and plasma (frozen until analysis)
      components. All assays were run using samples from every individual, and a nested
      analysis was used to partition variation/covariation at the levels of species and
      individuals within species. We detected positive correlations between
      functionally related measures of immunity within species, but these were absent
      from comparisons between species. A canonical correlation analysis revealed no
      significant relationships between the plasma and leukocyte assays at the levels
      of both individual and species, suggesting that these measures of immunity are
      neither competitive nor synergistic. We conclude that one measure of each assay
      type may be required to maximally characterize immune function in studies of a
      single species, while the same is not true in studies among species.

PMID- 16618675
TI  - Flexible diet choice offsets protein costs of pathogen resistance in a
      caterpillar.
AB  - Mounting effective resistance against pathogens is costly in terms of energy and
      nutrients. However, it remains unexplored whether hosts can offset such costs by
      adjusting their dietary intake so as to recoup the specific resources involved.
      We test this possibility by experimentally challenging caterpillars (Spodoptera
      littoralis) with a highly virulent entomopathogen (nucleopolyhedrovirus), under
      dietary regimes varying in the content of protein and digestible carbohydrate. We
      found that dietary protein influenced both resistance to pathogen attack and
      constitutive immune function to a greater extent than did dietary carbohydrate,
      indicating higher protein costs of resistance than energy costs. Moreover, when
      allowed to self-compose their diet, insects surviving viral challenge increased
      their relative intake of protein compared with controls and those larvae dying of
      infection, thus demonstrating compensation for protein costs associated with
      resistance. These results suggest that the change in the host's nutritional
      demands to fight infection induces a compensatory shift in feeding behaviour.

PMID- 16618676
TI  - Insect eggs exert rapid control over an oxygen-water tradeoff.
AB  - In terrestrial environments, the exchange of respiratory gases exacts a water
      cost: obtaining oxygen or carbon dioxide requires losing water. Insect eggs
      should be especially sensitive to this tradeoff-because they are unable to forage
      for water, have high surface area-to-volume ratios, and experience large
      temperature-driven changes in oxygen demand. Previous work from our laboratory,
      on eggs of a common hawk-moth, Manduca sexta, has shown that, during development,
      metabolic rate and water loss rates rise in parallel. These correlative data
      suggest that eggshell conductance increases to accommodate increasing metabolic
      demand. Here, we test this idea experimentally by subjecting eggs of M. sexta to
      15, 21 (normoxia) and 35% oxygen for 24h, while measuring rates of metabolism (as
      carbon dioxide emission) and water loss. Hypoxia depressed egg metabolic rates,
      but led to pronounced, rapid increases in water loss. By contrast, hyperoxia had
      no significant effect on metabolism or water loss. These data demonstrate that
      insect eggs actively participate in balancing oxygen gain and water loss, and
      that they use tissue oxygen status, or some correlate of it, as a cue for
      increasing eggshell conductance. Rapid control over conductance may allow eggs to
      conserve water during an initial period of low metabolic demand, thereby
      deferring water costs of respiratory gas exchange until late in development.

PMID- 16618677
TI  - Energetic demand of multiple dependents and the evolution of slow human growth.
AB  - This study investigates the consequences of the human foraging niche and multiple
      dependent offspring on the optimal growth trajectory of humans. We test the
      hypothesis that the human pattern of slow human growth between age at weaning and
      puberty helps defer the compound energetic demand on parents with multiple
      dependents, by using growth and demographic data from two foraging societies, the
      Ache of eastern Paraguay and the Dobe Ju/'hoansi of Botswana and Namibia. We run
      simulations of observed and potential growth trajectories among sub-adults and
      their consequent energetic demands on parents given profiles of fertility,
      mortality, consumption and production. We find that either sub-adult production
      or food subsidies from other people must substantially increase in order to
      compensate for the dramatic increase in energetic demand on parents if offspring
      were to grow faster at younger ages. Our conclusion is that slow human growth
      followed by a rapid adolescent growth spurt may have facilitated rising human
      fertility rates and greater investments in neural capital.

PMID- 16618678
TI  - Individual advantages to ecological specialization: insights on cognitive
      constraints from three conspecific taxa.
AB  - The information-processing hypothesis (IPH) posits that specialist herbivores
      should make host-associated decisions more effectively than generalists and thus
      enjoy associated fitness advantages that may help explain the evolutionary
      prevalence of host-specific insects. This is because generalists must evaluate a
      greater diversity of host plants/cues than specialists and thus face a cognitive
      challenge that is predicted to constrain the efficiency and accuracy of their
      choices. Here, we present the first individual-level evaluation of this
      hypothesis. This involved experimentally quantifying the specificity, efficiency,
      and accuracy of host selection, as both larvae and adults, for many individuals
      representing each of three 'host forms' of Neochlamisus bebbianae leaf beetles.
      These experiments provided several significant findings: host forms differed in
      larval specificity, with the more specialized host forms more efficiently and
      accurately selecting optimal hosts as both larvae and adults. Positive
      correlations between larval specificity and both efficiency and accuracy across
      test individuals provided the most direct evidence to date for a biological
      association between these variables. Our results thus provide strong and
      consistent support for the IPH at the level of both populations and individuals.
      Because individual N. bebbianae make many host-associated decisions in nature,
      our results suggest that cognitive constraints may play a major role in the
      evolutionary dynamics of ongoing ecological specialization and diversification in
      this species.

PMID- 16618679
TI  - UV matters in shoaling decisions.
AB  - Shoaling behaviour in fish is influenced by numerous factors, such as
      familiarity, kinship, group size and shoal composition. Grouping decisions are
      based on both olfactory and visual cues. The visual system of many vertebrates is
      extended into the ultraviolet (UV) wave range as in three-spined sticklebacks
      (Gasterosteus aculeatus, L.). We investigated whether the presence or absence of
      UV wavelengths has an influence on shoaling behaviour in this species.
      Reproductively non-active three-spined sticklebacks were given the choice between
      two shoals, equal in numbers of individuals, which could be seen either through a
      UV-transmitting [UV(+)] or a UV-blocking [UV(-)] filter. Test fish preferred to
      join the shoal seen under UV(+) conditions. Due to differences in quantal flux
      between the UV(+) and UV(-) filters used, control experiments with neutral
      density optical filters were performed in order to clarify the role of luminance.
      Here, test fish spent significantly more time near shoals that were seen in a
      darker environment, suggesting a potential trade-off between UV radiation and
      lower brightness during shoal choice. To our knowledge, these results demonstrate
      for the first time that shoaling decisions are influenced by UV wavelengths.

PMID- 16618680
TI  - Footprints in the sand: independent reduction of subdigital lamellae in the Namib
      Kalahari burrowing geckos.
AB  - Many desert organisms exhibit convergence, and certain physical factors such as
      windblown sands have generated remarkably similar ecomorphs across divergent
      lineages. The burrowing geckos Colopus, Chondrodactylus and Palmatogecko occupy
      dune ecosystems in the Namib and Kalahari deserts of southwest Africa. Considered
      closely related, they share several putative synapomorphies, including reduced
      subdigital pads (toe pads) and spinose digital scales. Though recognized as part
      of Africa's ecologically diverse Pachydactylus Group, the burrowing geckos'
      precise phylogenetic affinities remain elusive. Convergent pedal modification
      provides a tenable alternative explaining the geckos' derived terrestriality and
      adaptation to Namib and Kalahari sands. We generated a molecular phylogeny for
      the Pachydactylus Group to examine evolutionary relationships among the burrowing
      geckos and infer historical patterns of pedal character change. Bayesian and
      parsimony analyses revealed all three burrowing genera to be deeply nested within
      Pachydactylus, each genus belonging to a separate clade. Strong support for these
      distinct clades indicates ecomorphological adaptations for burrowing have evolved
      independently three times in the southern Pachydactylus Group. We argue that the
      physical properties of Namib and Kalahari sands played a principal role in
      selecting for pedal similarity.

PMID- 16618681
TI  - Visual search for a target changing in synchrony with an auditory signal.
AB  - We examined whether the detection of audio-visual temporal synchrony is
      determined by a pre-attentive parallel process, or by an attentive serial process
      using a visual search paradigm. We found that detection of a visual target that
      changed in synchrony with an auditory stimulus was gradually impaired as the
      number of unsynchronized visual distractors increased (experiment 1), whereas
      synchrony discrimination of an attended target in a pre-cued location was
      unaffected by the presence of distractors (experiment 2). The effect of
      distractors cannot be ascribed to reduced target visibility nor can the increase
      in false alarm rates be predicted by a noisy parallel processing model. Reaction
      times for target detection increased linearly with number of distractors, with
      the slope being about twice as steep for target-absent trials as for target
      present trials (experiment 3). Similar results were obtained regardless of
      whether the audio-visual stimulus consisted of visual flashes synchronized with
      amplitude-modulated pips, or of visual rotations synchronized with frequency
      modulated up-down sweeps. All of the results indicate that audio-visual
      perceptual synchrony is judged by a serial process and are consistent with the
      suggestion that audio-visual temporal synchrony is detected by a 'mid-level'
      feature matching process.

PMID- 16618682
TI  - Context-dependent vocal mimicry in a passerine bird.
AB  - How do birds select the sounds they mimic, and in what contexts do they use vocal
      mimicry? Some birds show a preference for mimicking other species' alarm notes,
      especially in situations when they appear to be alarmed. Yet no study has
      demonstrated that birds change the call types they mimic with changing contexts.
      We found that greater racket-tailed drongos (Dicrurus paradiseus) in the
      rainforest of Sri Lanka mimic the calls of predators and the alarm-associated
      calls of other species more often than would be expected from the frequency of
      these sounds in the acoustic environment. Drongos include this alarm-associated
      mimicry in their own alarm vocalizations, while incorporating other species'
      songs and contact calls in their own songs. Drongos show an additional level of
      context specificity by mimicking other species' ground predator-specific call
      types when mobbing. We suggest that drongos learn other species' calls and their
      contexts while interacting with these species in mixed flocks. The drongos'
      behaviour demonstrates that alarm-associated calls can have learned components,
      and that birds can learn the appropriate usage of calls that encode different
      types of information.

PMID- 16618683
TI  - Why is stress so deadly? An evolutionary perspective.
AB  - The reaction of the body to prolonged stress has many harmful effects. Classical
      theory assumes that stress responses have evolved due to their short-term
      selective advantages ('flight or fight'), and despite their adverse long-term
      effects. In contrast, we demonstrate that the adverse effects of stress responses
      may have a selective advantage. Using an analytical model we show that a gene
      that causes the early death of a relatively unfit individual can increase in
      frequency in a structured population even if it has no positive effect on that
      individual. This result offers a new perspective on the relations between stress
      factors, stress responses and stress-related diseases.

PMID- 16618684
TI  - Beyond barcodes: complex DNA taxonomy of a South Pacific Island radiation.
AB  - DNA barcodes can provide rapid species identification and aid species inventories
      in taxonomically unstudied groups. However, the approach may fail in recently
      diverged groups with complex gene histories, such as those typically found on
      oceanic islands. We produced a DNA-based inventory of taxonomically little known
      diving beetles (genus Copelatus) in the Fiji archipelago, where they are a
      dominant component of the aquatic invertebrate fauna. Sampling from 25 localities
      on five islands and analysis of sequences from one nuclear (328bp histone 3) and
      three mitochondrial (492bp rrnL, 786bp cox1, 333bp cob) gene regions revealed
      high haplotype diversity, mainly originated since the Pleistocene, and subdivided
      into three major phylogenetic lineages and 22 statistical parsimony networks. A
      traditional taxonomic study delineated 25 morphologically defined species that
      were largely incongruent with the DNA-based groups. Haplotype diversity and their
      spatial arrangement demonstrated a continuum of relatedness in Fijian Copelatus,
      with evidence for introgression at various hierarchical levels. The study
      illustrates the difficulties for formal classification in evolutionarily complex
      lineages, and the potentially misleading conclusions obtained from either DNA
      barcodes or morphological traits alone. However, the sequence profile of Fijian
      Copelatus provides an evolutionary framework for the group and a DNA-based
      reference system for the integration of ecological and other biodiversity data,
      independent of the Linnaean naming system.

PMID- 16618685
TI  - Secondary traumatic stress and oncology social work: protecting compassion from
      fatigue and compromising the worker's worldview.
AB  - Secondary traumatic stress (STS) represents a disorder that has the same symptoms
      as post traumatic stress disorder, but results from vicariously experiencing
      trauma through association with those directly encountering the traumatic
      event(s). This exploratory study examined STS in 21 oncology social workers who
      were members of the Association of Oncology Social Workers. The results of this
      study revealed that oncology social workers experienced compassion fatigue and
      burnout and that these variables were inversely related to compassion
      satisfaction. Other relationships between emotional involvement, ability to
      separate work from home, level of licensure, personal loss, and empathetic
      responsiveness were also examined.

PMID- 16618686
TI  - Social support, affectivity, and the quality of life of patients and their
      support-givers prior to stem cell transplantation.
AB  - PURPOSE: To determine differences and interdependencies between patients and
      their support-givers prior to PBSCT. METHOD: Patients and their principal support
      givers completed the Illness- Specific Social Support Scale (ISSS), the Profile
      of Mood States, and the EORTC QLQ-C30. RESULTS: One hundred fifty-five of 200
      eligible patients replied. They nominated spouse/partner (70.6%), friends, and
      children as principal support source. Patients receiving social support from
      spouses reported a better HRQoL than patients who nominated other persons as the
      principal source of social support. Patients perceived more positive (p < .01)
      and more problematic (p < .05) social interactions than support-givers. The
      support-givers nominated: children (25.8%), spouse/partner, and siblings.
      Analysis showed an additional effect of gender and support-giving role (female
      patients scored worst in overall QoL, male support- givers best). CONCLUSION:
      Psychotherapeutic interventions should not only address the patients' problems
      but also the support-givers' questions, needs, and psychosocial burdens.

PMID- 16618687
TI  - Patient-physician communication regarding use of complementary therapies during
      cancer treatment.
AB  - It is estimated that as many as 80% of adult cancer patients use at least one
      form of Complementary and Alternative Medicine (CAM) during or after conventional
      treatment. Studies of physician-patient communication about the use of CAM have
      concluded that patients frequently do not tell their oncologists about their use
      of CAM and physicians consistently underestimate the numbers of their patients
      using CAM. The purpose of this multi-site study was to assess newly diagnosed
      cancer patients' and oncologists' communication practices with regard to
      complementary therapies. Patients (106 breast and 82 prostate) indicated which of
      45 complementary therapies they were using while physicians at their institutions
      indicated which they supported. It is noted that, although we use the popular
      acronym "CAM" all patients surveyed were receiving conventional medical
      treatment. Thus, the survey addressed complementary therapies only. A large
      majority (84%) indicated they were using at least one therapy with the most
      popular being exercise, vitamins, prayer, and nutritional supplements.
      Surprisingly, the oncologists surveyed were generally enthusiastic and supportive
      of patients' use of complementary therapies. In addition to those therapies
      popular with patients, at least half the physicians supported massage, journal
      writing, support groups, acupuncture, biofeedback, and art therapy. However,
      discussions of CAM are relatively rare and most likely to be initiated by
      patients. When the topic is discussed, both patients and doctors say it usually
      enhances their relationship. Implications for CAM program development and
      oncology professionals' roles in patient education regarding complementary
      therapies are presented.

PMID- 16618688
TI  - Effects of an education program on radiation oncology patients and families.
AB  - Patients and family members in a radiation oncology department participated in a
      study of a new education/orientation program. Information was presented in oral
      and in written form. After the intervention, orientation program participants did
      not differ significantly from control group members in state anxiety, general
      distress, treatment adherence, or knowledge of radiation therapy. Orientation
      group patients reported greater satisfaction with clinic care, and the
      orientation group was significantly more likely to utilize psychological
      counseling services within the clinic, as well as outside support. Discussion
      focused on possible explanations for the strikingly favorable program evaluations
      given by participants despite little evidence that the program was of significant
      benefit.

PMID- 16618689
TI  - Man to man and side by side, they cope with prostate cancer: self-help and social
      support.
AB  - Prostate cancer affects men and their loved ones; consequently, survivors and
      their wives can gain from social support throughout the illness experience. After
      observing meetings of a support group for prostate cancer survivors and their
      partners, the authors used the constant comparison method to draw conclusions
      about the types of support generated in the men's and women's divisions of the
      group. The authors concluded that both divisions served as sites of information
      but not as scenes of practical assistance. The authors also found that the
      discursive practices of the groups and the structural elements of the group
      meetings inhibited emotional support through topic turning, comparisons between
      members, and the role of group facilitators. The authors consider the study's
      implications for support group leaders and scholars.

PMID- 16618690
TI  - The relationships between satisfaction with social support, affect balance, and
      hope in cancer patients.
AB  - The present study investigated relationships between cancer patients'
      satisfaction with social support, and their affect and levels of hope. Cancer
      patients completed measures describing their hope and affect, and a structured
      interview was conducted to ascertain their level of satisfaction with the support
      they were receiving. Results indicated that support satisfaction accounted for a
      statistically significant proportion of the variance in patient hope and affect,
      although other variables emerged as more powerful predictors.

PMID- 16618692
TI  - Exposure, relaxation, and rescripting treatment for trauma-related nighmares.
AB  - Trauma victims frequently report sleep disturbances, including nightmares,
      following traumatic events. Research indicates that nightmares are associated
      with the level and severity of other indices of distress. The recognition of the
      prominence of trauma-related nightmares, in prevalence and impact, has in part
      heightened efforts to develop and assess techniques to alleviate these
      difficulties. The majority of such previous efforts were predominantly case
      studies or uncontrolled group studies; however, recently several controlled
      studies have been conducted. The treatment with the most empirical support is
      generally called imagery rehearsal therapy (IRT). This treatment commonly
      involves relaxation procedures, limited exposure to the nightmare content,
      rewriting the content of the nightmare, and rehearsal of the altered content.
      This article provides a description of a modified version of IRT that
      incorporates all these techniques, with an enhanced exposure component and the
      addition of trauma themes and alteration of sleep habits. Guidelines for
      application with clients are outlined. A case study and case series were
      completed on this variant of IRT and a randomized clinical trial is currently
      underway.

PMID- 16618693
TI  - Dissociative symptomatology in posttraumatic stress disorder and disorders of
      extreme stress.
AB  - The present study was designed to assess differences in dissociative symptoms in
      adults with Posttraumatic Stress Disorder (PTSD) vs. PTSD plus Disorders of
      Extreme Stress Not Otherwise Specified (DESNOS). This study was done for two
      reasons: (1) to better understand the clinical profile of DESNOS clients in order
      to inform more effective treatment, and (2) to further empirical research on the
      validity of the DESNOS construct. To assess severity of dissociative symptoms,
      the authors administered the Dissociative Experiences Scale (DES) to 155
      participants with PTSD. Using the Structured Interview for Disorders of Extreme
      Stress (SIDES), participants were divided into two groups: those who also met
      criteria for DESNOS and those who did not. DES means are provided for the two
      groups. Participants with PTSD plus DESNOS scored higher than participants with
      only PTSD on the measure of dissociative symptomatology, particularly on the DES
      scales that tap absorption/fantasy and depersonalization/derealization. The two
      groups did not differ on the amnesia subscale of the DES. Findings support the
      construct validity of the DESNOS concept and further delineate the clinical
      profiles of community-based PTSD with and without DESNOS, thus contributing to
      the knowledge base on the assessment of complex adaptations to trauma.

PMID- 16618694
TI  - Mental health services and sexual abuse: the need for staff training.
AB  - Identification of child abuse by mental health services is important for
      formulation of the causes of presenting problems and for development of
      comprehensive treatment plans. A small but growing number of studies suggest,
      however, that the majority of child sexual abuse cases are not identified by
      mental health services. A similarly small literature also suggests that abuse
      survivors are extremely reluctant to spontaneously tell anyone about the abuse,
      indicating that professionals have a responsibility to ask rather than wait for
      spontaneous disclosures. The purpose of this study, therefore, was to add to
      these two bodies of literature with a New Zealand sample. A postal questionnaire
      was completed by 191 women who had received counselling for childhood sexual
      abuse. The average amount of time taken to tell anyone about the abuse was 16
      years. Only 22% of those who had been in contact with public mental health
      services had ever been asked about abuse by those services. It was concluded that
      New Zealand women are reluctant to disclose abuse and that mental health services
      are, as is the case elsewhere, failing to assist them with this process. The need
      for staff training is discussed, and an example described.

PMID- 16618695
TI  - Frequency, clinical and demographic correlates of pathological dissociation in
      Europe.
AB  - Although pathological dissociation (PD) has received increasing scientific
      attention in Anglo-American countries, European research on the frequency,
      clinical and demographic correlates of this discontinuous construct are lacking.
      An 8-item subscale of the Dissociative Experiences Scale, called the DES-Taxon,
      was administered to five samples comprising a non-clinical population, students,
      unselected psychiatric inpatients, eating-disordered inpatients and psychosomatic
      outpatients with a total of 1,759 adult participants. In the two non-clinical
      samples, the frequency of PD ranged between 0.3 and 1.8%. Its prevalence was
      highest in the psychiatric inpatients (5.4%) followed by the eating disorders
      (4.8%) and the psychosomatic outpatients (2.2%). PD was seen in all diagnostic
      groups and it was associated with more psychopathological distress and younger
      age. PD is frequently found in clinical populations in European countries, too.
      However, methodological problems relating to its empirical determination might
      obscure the clinical and scientific value of the construct.

PMID- 16618696
TI  - Assessment of genuine and simulated dissociative identity disorder on the
      structured interview of reported symptoms.
AB  - Little is known about how to detect malingered dissociative identity disorder
      (DID). This study presents preliminary data from an ongoing study about the
      performance of DID patients on the Structured Interview of Reported Symptoms
      (SIRS, Rogers, Bagby, & Dickens, 1992), considered to be a "gold standard"
      structured interview in forensic psychology to detect feigning of psychological
      symptoms. Test responses from 20 dissociative identity disorder (DID) patients
      are compared to those of 43 well informed and motivated DID simulators. Both the
      simulators and DID patients endorsed such a high number of symptoms that their
      average overall scores would typically be interpreted as indicative of feigning.
      The simulators' mean scores were significantly higher than those of the DID
      patients on only four out of 13 scales. These results provide preliminary
      evidence that well informed and motivated simulators are able to fairly
      successfully simulate DID patients and avoid detection on the SIRS. Furthermore,
      many DID patients may be at risk for being inaccurately labeled as feigning on
      the SIRS.

PMID- 16618697
TI  - The influence of current stress on dissociative experiences: an exploratory study
      in a non-clinical population.
AB  - In this study, the relationship between current stress, as perceived by an
      individual, and dissociative phenomena is explored. All subjects were in an acute
      and naturally caused stress-situation-sudden threat of dismissal from their jobs
      in a large multinational corporation. Dissociation and stress were measured at
      two different times over three months. Since information campaigns and
      psychological support programs were offered to all participants, levels of stress
      were expected to decrease significantly. The data show that dissociative
      experiences are elevated when subjects experience high levels of current stress,
      though scores fall within the normal non-pathological range. Furthermore, it
      appears that a decrease in stress level is associated with a significant decrease
      of dissociative symptoms. The results support a one-directional causal
      relationship: a decrease in perceived stress leads to a decrease in dissociative
      phenomena.

PMID- 16618699
TI  - Cyanidin-3-glucoside, a natural product derived from blackberry, exhibits
      chemopreventive and chemotherapeutic activity.
AB  - Epidemiological data suggest that consumption of fruits and vegetables has been
      associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a
      compound found in blackberry and other food products, was shown to possess
      chemopreventive and chemotherapeutic activity in the present study. In cultured
      JB6 cells, C3G was able to scavenge ultraviolet B-induced *OH and O2-* radicals.
      In vivo studies indicated that C3G treatment decreased the number of non
      malignant and malignant skin tumors per mouse induced by 12-O
      tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated
      mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced
      transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and
      tumor necrosis factor-alpha. These inhibitory effects appear to be mediated
      through the inhibition of MAPK activity. C3G also blocked TPA-induced neoplastic
      transformation in JB6 cells. In addition, C3G inhibited proliferation of a human
      lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size
      of A549 tumor xenograft growth and significantly inhibited metastasis in nude
      mice. Mechanistic studies indicated that C3G inhibited migration and invasion of
      A549 tumor cells. These finding demonstrate for the first time that a purified
      compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor
      metastasis in vivo.

PMID- 16618700
TI  - Heat shock induces apoptosis independently of any known initiator caspase
      activating complex.
AB  - Adaptive responses to mild heat shock are among the most widely conserved and
      studied in nature. More intense heat shock, however, induces apoptosis through
      mechanisms that remain largely unknown. Herein, we present evidence that heat
      shock activates an apical protease that stimulates mitochondrial outer membrane
      permeabilization and processing of the effector caspase-3 in a benzyloxycarbonyl
      VAD-fluoromethyl ketone (polycaspase inhibitor)- and Bcl-2-inhibitable manner.
      Surprisingly, however, neither FADD.caspase-8 nor RAIDD.caspase-2 PIDDosome (p53
      induced protein with a death domain) complexes were detected in dying cells, and
      neither of these initiator caspases nor the endoplasmic reticulum stress
      activated caspases-4/12 were required for mitochondrial outer membrane
      permeabilization. Similarly, although cytochrome c was released from mitochondria
      following heat shock, functional Apaf-1.caspase-9 apoptosome complexes were not
      formed, and caspase-9 was not essential for the activation of caspase-3 or the
      induction of apoptosis. Thus, heat shock does not require any of the known
      initiator caspases or their activating complexes to promote apoptotic cell death
      but instead relies upon the activation of an apparently novel apical protease
      with caspase-like activity.

PMID- 16618701
TI  - Transcription regulation of ompF and ompC by a single transcription factor, OmpR.
AB  - The ompF and ompC genes of Escherichia coli are reciprocally regulated by a
      single transcription factor, phosphorylated OmpR (OmpR-P), depending upon medium
      osmolarity. This regulation involves activation of ompF and its repression with
      concomitant activation of ompC. This occurs through OmpR-P binding to four (F1,
      F2, F3, and F4) and three (C1, C2, and C3) sites located upstream of the ompF and
      ompC promoters, respectively, through a novel mechanism. Here we show that there
      is a distinct OmpR-P binding hierarchy within F1, F2, and F3 sites as well as
      within C1, C2, and C3 sites. Each of these sites contains two tandem 10-bp OmpR-P
      binding subsites, a-site and b-site (from 5' to 3' direction). OmpR-P has higher
      affinity to the downstream b-site than to the upstream a-site in each case. Six
      OmpR-P molecules bind to F and C sites two-by-two in a discontinuous "galloping"
      manner. We propose that this tight hierarchical binding of a transcription
      factor, OmpR, allows distinct stepwise regulation of ompF and ompC transcription,
      which minimizes their overlapping expression upon changes in the medium
      osmolarity to achieve the reciprocal expression of ompF and ompC.

PMID- 16618702
TI  - Clathrin-mediated endocytosis and lysosomal cleavage of hepatitis B virus capsid
      like core particles.
AB  - The hepatitis B virus (HBV) core particle serves as a protective capsid shell for
      the viral genome and is highly immunogenic. Recombinant capsid-like core
      particles are used as effective carriers of foreign T and B cell epitopes and as
      delivery vehicles for oligonucleotides. The core monomer contains an arginine
      rich C terminus that directs core particle attachment to cells via membrane
      heparan sulfate proteoglycans. Here we investigated the mechanism of recombinant
      core particle uptake and its intracellular fate following heparan sulfate
      binding. We found that the core particles are internalized in an energy-dependent
      manner. Core particle uptake is inhibited by chlorpromazine and by cytosol
      acidification known to block clathrin-mediated endocytosis but not by nystatin,
      which blocks lipid raft endocytosis. Particle uptake is abolished by expression
      of dominant negative forms of eps15 and Rab5, adaptors involved in clathrin
      mediated endocytosis and early endosome transport, respectively. Endocytosed
      particles are transported to lysosomes where the core monomer is
      endoproteolytically cleaved into its distinct domains. Using protease inhibitors,
      cathepsin B was identified as the enzyme responsible for core monomer cleavage.
      Finally we found that monomer cleavage promotes particle dissociation within
      cells. Together, our results show that HBV capsid-like core particles are
      internalized through clathrin-mediated endocytosis, leading to lysosomal cleavage
      of the core monomer and particle dissociation.

PMID- 16618704
TI  - FRET analysis of in vivo dimerization by RNA-editing enzymes.
AB  - Members of the ADAR (adenosine deaminase that acts on RNA) enzyme family catalyze
      the hydrolytic deamination of adenosine to inosine within double-stranded RNAs, a
      poorly understood process that is critical to mammalian development. We have
      performed fluorescence resonance energy transfer experiments in mammalian cells
      transfected with fluorophore-bearing ADAR1 and ADAR2 fusion proteins to
      investigate the relationship between these proteins. These studies conclusively
      demonstrate the homodimerization of ADAR1 and ADAR2 and also show that ADAR1 and
      ADAR2 form heterodimers in human cells. RNase treatment of cells expressing these
      fusion proteins changes their localization but does not affect dimerization.
      Taken together these results suggest that homo- and heterodimerization are
      important for the activity of ADAR family members in vivo and that these
      associations are RNA independent.

PMID- 16618703
TI  - Focal adhesions in (myo)fibroblasts scaffold adenylyl cyclase with phosphorylated
      caveolin.
AB  - Fibroblast-myofibroblast transformation, a critical event for enhanced
      extracellular matrix deposition, involves formation of an actin stress fiber
      contractile apparatus that radiates from focal adhesions (FA) in the plasma
      membrane. Activation of adenylyl cyclase (AC, i.e. increases in cAMP) negatively
      regulates such transformation. Caveolae and their resident protein caveolins
      scaffold signaling molecules, including AC isoforms, whereas phosphorylated
      caveolin-1 (phospho-cav-1) may localize at FA. Here, we used adult rat cardiac
      fibroblasts to examine distribution and expression of AC, phospho-cav-1, and FA
      proteins to define mechanisms that link increases in cAMP to caveolin-1
      phosphorylation, actin/FA assembly, and fibroblast-myofibroblast transformation.
      Sucrose density gradient centrifugation, immunoblot, and immunohistochemical
      analysis revealed that, unlike cav-1, phospho-cav-1 enriches in membrane
      fractions that express FA proteins and localize at the ends of actin stress
      fibers. We detected AC in both cav-1 and phospho-cav-1 immunoprecipitates, but FA
      kinase (FAK), phospho-FAK (FAK Tyr-397), paxillin, and vinculin were detected
      only in phospho-cav-1 immunoprecipitates. Treatment with the AC activator
      forskolin or a cAMP analog increased cav-1 phosphorylation but decreased FAK Tyr
      397 phosphorylation in a cAMP-dependent protein kinase-dependent manner. These
      events preceded actin cytoskeletal disruption, an effect that was blocked by
      small interfering RNA knock-down of cav-1. Inhibition of protein tyrosine
      phosphatase 1B abrogated cAMP-mediated disruption of actin cytoskeleton, cav-1
      phosphorylation, and FAK Tyr-397 dephosphorylation. The data thus define a novel
      organization of signaling molecules that regulate fibroblasts: scaffolding of AC
      by phospho-cav-1 at FA sites in a caveolae-free microdomain along with components
      that mediate inhibition of actin/FA assembly and fibroblast-myofibroblast
      transformation via increases in cAMP.

PMID- 16618705
TI  - Roles of the active site water, histidine 303, and phenylalanine 396 in the
      catalytic mechanism of the elongation condensing enzyme of Streptococcus
      pneumoniae.
AB  - beta-Ketoacyl-ACP synthases catalyze the condensation steps in fatty acid and
      polyketide synthesis and are targets for the development of novel antibiotics and
      anti-obesity and anti-cancer agents. The roles of the active site residues in
      Streptococcus pneumoniae FabF (beta-ketoacyl-ACP synthase II; SpFabF) were
      investigated to clarify the mechanism for this enzyme superfamily. The
      nucleophilic cysteine of the active site triad was required for acyl-enzyme
      formation and the overall condensation activity. The two active site histidines
      in the elongation condensing enzyme have different electronic states and
      functions. His337 is essential for condensation activity, and its protonated
      Nepsilon stabilizes the negative charge developed on the malonyl thioester
      carbonyl in the transition state. The Nepsilon of His303 accelerated catalysis by
      deprotonating a structured active site water for nucleophilic attack on the C3 of
      malonate, releasing bicarbonate. Lys332 controls the electronic state of His303
      and also plays a critical role in the positioning of His337. Phe396 functions as
      a gatekeeper that controls the order of substrate addition. These data assign
      specific roles for each active site residue and lead to a revised general
      mechanism for this important class of enzymes.

PMID- 16618706
TI  - Make it HuGE: human genome epidemiology reviews, population health, and the IJE.

PMID- 16618708
TI  - Benefits of influenza vaccine in US elderly--appreciating issues of confounding
      bias and precision.

PMID- 16618709
TI  - Commentary: guinea-pigs' private war.

PMID- 16618710
TI  - The DNA damage response arouses the immune system.
AB  - Although there is considerable knowledge of how DNA damage triggers cell cycle
      arrest, DNA repair, and apoptosis, little was known about its potential role in
      immune responses. Recently, we showed that genotoxic stress and stalled DNA
      replication forks induce the expression of ligands for the NKG2D receptor found
      in natural killer cells and certain T cells, cell types that are able to attack
      tumor cells. Chronic activation of this response in tumor cells may contribute to
      immune recognition, but it also imposes a selection mechanism for immune escape
      and malignant progression. This unique arm of the DNA damage response may have
      implications for understanding therapeutic responses, many of which induce the
      DNA damage response, and for designing more effective regimens to treat cancer.

PMID- 16618711
TI  - Akt signaling and cancer: surviving but not moving on.
AB  - The frequent deregulation of the phosphoinositide 3-kinase/Akt survival signaling
      pathway in cancer has prompted significant interest in blocking this pathway to
      treat cancer. Recently, however, two studies have shown that the Akt isoform Akt1
      limits the invasive migration of breast cancer cells. These studies suggest that
      Akt1 may have a dual role in tumorigenesis, acting not only pro-oncogenically by
      suppressing apoptosis but also anti-oncogenically by suppressing invasion and
      metastasis. We discuss the possible implications of these findings for
      therapeutic development of Akt inhibitors to treat cancer.

PMID- 16618712
TI  - Antiangiogenesis and drug delivery to tumors: bench to bedside and back.
AB  - After over 30 years of preclinical and clinical development, antiangiogenic
      agents have recently entered the clinic as attractive targeted therapeutics for
      the treatment of cancer. Fueled by exciting new developments in the field, the
      AACR Special Conference was designed to broadly survey critical scientific
      advances in the antiangiogenic therapy of cancer. Because these advances have
      come primarily with the use of combinations of antiangiogenic agents with
      chemotherapy, or with antiangiogenic agents that also directly target the cancer
      cells, the central theme included the issue of drug delivery to tumors. These two
      major issues were addressed in concert, from basic mechanisms of action of
      antiangiogenic agents to new combination approaches to cancer treatment. Nearly
      300 participants from 20 countries registered for the conference, drawn both from
      academia and industry, with a wide range in experience and background. Dr. Rakesh
      Jain, along with conference co-chairs, Drs. Lee Ellis and Luisa Iruela-Arispe,
      assembled an outstanding lineup of speakers for this conference that included
      many of the pioneers in the fields of angiogenesis and drug delivery from the
      U.S. and abroad. This resulted in an excellent overview of the advances in our
      understanding of cellular and molecular aspects of tumor angiogenesis and
      antiangiogenic therapy of cancer in combination with conventional therapy.

PMID- 16618713
TI  - Placenta growth factor overexpression inhibits tumor growth, angiogenesis, and
      metastasis by depleting vascular endothelial growth factor homodimers in
      orthotopic mouse models.
AB  - The role of placenta growth factor (PlGF) in pathologic angiogenesis is
      controversial. The effects of PlGF on growth, angiogenesis, and metastasis from
      orthotopic tumors are not known. To this end, we stably transfected three human
      cancer cell lines (A549 lung, HCT116 colon, and U87-MG glioblastoma) with human
      plgf-2 full-length cDNA. Overexpression of PlGF did not affect tumor cell
      proliferation or migration in vitro. The growth of PlGF-overexpressing tumors
      grown orthotopically or ectopically was impaired in all three tumor models. This
      decrease in tumor growth correlated with a decrease in tumor angiogenesis. The
      PlGF-overexpressing tumors had decreased vessel density and increased vessel
      diameter, but vessel permeability was not different from the parental tumors.
      Tumors overexpressing PlGF exhibited higher levels of PlGF homodimers and
      PlGF/vascular endothelial growth factor (VEGF) heterodimers but decreased levels
      of VEGF homodimers. Our study shows that PlGF overexpression decreases VEGF
      homodimer formation and inhibits tumor progression.

PMID- 16618714
TI  - Methylation of the IL-12Rbeta2 gene as novel tumor escape mechanism for pediatric
      B-acute lymphoblastic leukemia cells.
AB  - Previous studies have shown that the interleukin-12 receptor beta2 (IL-12Rbeta2)
      gene is expressed in normal naive, germinal center and memory B cells but not in
      their malignant counterparts. The aim of this study was to investigate (i)
      whether the IL-12Rbeta2 gene is silenced in B-cell acute lymphoblastic leukemia
      (B-ALL) cells, and (ii) what the functional implications of such silencing for
      tumor growth are. Here, we show that although mature B cells expressed both
      chains of the IL-12R, normal pro-B and pre-B cells failed to express the IL
      12Rbeta2 chain. Similarly, primary tumor cells from pediatric pro-B, early pre-B,
      and pre-B ALL (30 cases) did not express the IL-12Rbeta2 chain. IL-12Rbeta2 gene
      silencing in B-ALL was found to depend on methylation of a CpG island in exon 1.
      Such methylation was not detected in normal early B cells that when
      differentiated into mature B cells expressed the IL-12Rbeta2 gene. Detection of
      IL-12Rbeta2 mRNA and protein in the tumorigenic 697 pre-B-ALL cell line allowed
      to perform functional experiments in severe combined immunodeficient/nonobese
      diabetic mice receiving 697 cells with or without human recombinant IL-12 (hrIL
      12). hrIL-12 administration reduced tumor growth and metastasis through
      antiproliferative and proapoptotic rather than antiangiogenic, activities. In
      conclusion, epigenetic silencing of the IL-12Rbeta2 gene represents a novel
      mechanism of tumor escape for B-ALL cells.

PMID- 16618715
TI  - Reactivation of developmentally expressed p63 isoforms predisposes to tumor
      development and progression.
AB  - Genes that are active during normal development are frequently reactivated during
      neoplastic transformation. We now report that developmentally expressed TAp63
      isoforms are frequently reactivated in human squamous cell carcinomas. To
      determine the consequences of TAp63 reactivation, we induced TAp63alpha
      expression during chemically-induced skin carcinogenesis. Deregulated TAp63alpha
      expression dramatically accelerated tumor development and progression, frequently
      resulting in epithelial-mesenchymal transitions to spindle cell carcinomas and
      lung metastases. Consistent with this observation, we detected high levels of
      Twist and N-cadherin in tumors overexpressing TAp63alpha. Thus, as observed for
      other developmental pathways, aberrant reactivation of TAp63 predisposes to tumor
      development and progression.

PMID- 16618716
TI  - A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant
      gliomas after alkylator chemotherapy.
AB  - Malignant gliomas have a very poor prognosis. The current standard of care for
      these cancers consists of extended adjuvant treatment with the alkylating agent
      temozolomide after surgical resection and radiotherapy. Although a statistically
      significant increase in survival has been reported with this regimen, nearly all
      gliomas recur and become insensitive to further treatment with this class of
      agents. We sequenced 500 kb of genomic DNA corresponding to the kinase domains of
      518 protein kinases in each of nine gliomas. Large numbers of somatic mutations
      were observed in two gliomas recurrent after alkylating agent treatment. The
      pattern of mutations in these cases showed strong similarity to that induced by
      alkylating agents in experimental systems. Further investigation revealed
      inactivating somatic mutations of the mismatch repair gene MSH6 in each case. We
      propose that inactivating somatic mutations of MSH6 confer resistance to
      alkylating agents in gliomas in vivo and concurrently unleash accelerated
      mutagenesis in resistant clones as a consequence of continued exposure to
      alkylating agents in the presence of defective mismatch repair. The evidence
      therefore suggests that when MSH6 is inactivated in gliomas, alkylating agents
      convert from induction of tumor cell death to promotion of neoplastic
      progression. These observations highlight the potential of large scale sequencing
      for revealing and elucidating mutagenic processes operative in individual human
      cancers.

PMID- 16618718
TI  - Immunoglobulin heavy chain locus events and expression of activation-induced
      cytidine deaminase in epithelial breast cancer cell lines.
AB  - When cells transform, phenotypic and genetic profiles can be dramatically
      altered. Nevertheless, a recent report identifying IgG in breast cancer cells was
      unexpected, revealing differentiation features normally associated with B
      lymphocytes. To extend these findings, we focused on immunoglobulin variable (V)
      region gene analysis using well-defined breast cancer cell lines expressing the
      epithelial marker, epithelial cell adhesion molecule (EpCAM). V(H) gene
      transcripts were identifiable by nested reverse transcription-PCR either as
      single or dual V, diversity (D), and joining (J) rearrangements in four of six
      lines, most being potentially functional. V(D)J transcripts were observed in
      sequential cultures, indicating stable expression. To exclude coexisting
      lymphocytes, each cell line was shown to be EBV negative, with CD19/CD20 and
      cytoplasmic/surface immunoglobulin also absent by flow cytometry. Identified V(H)
      transcripts were then sought in individual tumor cells, isolated as EpCAM+ single
      cells by flow cytometry. Importantly, in three of three selected cell lines, V(H)
      genes were identifiable in a significant fraction (approximately 32%) of single
      cells. In five of six identified V(H) genes, somatic mutations were apparent with
      no intraclonal variation, indicating cessation of mutational activity. V(H)
      transcripts were pre- and post-isotype switch, with activation of switch events
      evident from expressed germ-line switch transcripts in two of six lines.
      Strikingly, six of six cell lines expressed activation-induced cytidine deaminase
      (AID) essential for mutational and switch activity. These data suggest either a
      de novo rearrangement and modification of V(H) genes in epithelial tumor cells or
      assimilation of lymphocyte-derived chromatin. Constitutive AID activation in
      malignant epithelial cells further raises a potential for inducing aberrant
      mutational activity.

PMID- 16618717
TI  - KRAS mutation status is predictive of response to cetuximab therapy in colorectal
      cancer.
AB  - The anti-epidermal growth factor receptor (anti-EGFR) cetuximab has been proven
      to be efficient in metastatic colorectal cancer. The molecular mechanisms
      underlying the clinical response to this drug remain unknown. Genetic alterations
      of the intracellular effectors involved in EGFR-related signaling pathways may
      have an effect on response to this targeted therapy. In this study, tumors from
      30 metastatic colorectal cancer patients treated by cetuximab were screened for
      KRAS, BRAF, and PIK3CA mutation by direct sequencing and for EGFR copy number by
      chromogenic in situ hybridization. Eleven of the 30 patients (37%) responded to
      cetuximab. A KRAS mutation was found in 13 tumors (43%) and was significantly
      associated with the absence of response to cetuximab (KRAS mutation in 0% of the
      11 responder patients versus 68.4% of the 19 nonresponder patients; P = 0.0003).
      The overall survival of patients without KRAS mutation in their tumor was
      significantly higher compared with those patients with a mutated tumor (P =
      0.016; median, 16.3 versus 6.9 months). An increased EGFR copy number was found
      in 3 patients (10%) and was significantly associated with an objective tumor
      response to cetuximab (P = 0.04). In conclusion, in this study, KRAS mutations
      are a predictor of resistance to cetuximab therapy and are associated with a
      worse prognosis. The EGFR amplification, which is not as frequent as initially
      reported, is also associated with response to this treatment.

PMID- 16618719
TI  - Multiple adaptive mechanisms to chronic liver disease revealed at early stages of
      liver carcinogenesis in the Mdr2-knockout mice.
AB  - Molecular events preceding the development of hepatocellular carcinoma were
      studied in the Mdr2-knockout (Mdr2-KO) mice. These mice lack the liver-specific P
      glycoprotein responsible for phosphatidylcholine transport across the canalicular
      membrane. Portal inflammation ensues at an early age followed by hepatocellular
      carcinoma development after the age of 1 year. Liver tissue samples of Mdr2-KO
      mice in the early and late precancerous stages of liver disease were subjected to
      histologic, biochemical, and gene expression profiling analysis. In an early
      stage, multiple protective mechanisms were found, including induction of many
      anti-inflammatory and antioxidant genes and increase of total antioxidant
      capacity of liver tissue. Despite stimulation of hepatocyte DNA replication,
      their mitotic activity was blocked at this stage. In the late stage of the
      disease, although the total antioxidant capacity of liver tissue of Mdr2-KO mice
      was normal, and inflammation was less prominent, many protective genes remained
      overexpressed. Increased mitotic activity of hepatocytes resulted in multiple
      dysplastic nodules, some of them being steatotic. Expression of many genes
      regulating lipid and phospholipid metabolism was distorted, including up
      regulation of choline kinase A, a known oncogene. Many other oncogenes, including
      cyclin D1, Jun, and some Ras homologues, were up-regulated in Mdr2-KO mice at
      both stages of liver disease. However, we found no increase of Ras activation.
      Our data suggest that some of the adaptive mechanisms induced in the early stages
      of hepatic disease, which protect the liver from injury, could have an effect in
      hepatocarcinogenesis at later stages of the disease in this hepatocellular
      carcinoma model.

PMID- 16618720
TI  - Sex-determining region Y box 4 is a transforming oncogene in human prostate
      cancer cells.
AB  - Prostate cancer is the most commonly diagnosed noncutaneous neoplasm and second
      most common cause of cancer-related mortality in western men. To investigate the
      mechanisms of prostate cancer development and progression, we did expression
      profiling of human prostate cancer and benign tissues. We show that the SOX4 is
      overexpressed in prostate tumor samples compared with benign tissues by
      microarray analysis, real-time PCR, and immunohistochemistry. We also show that
      SOX4 expression is highly correlated with Gleason score at the mRNA and protein
      level using tissue microarrays. Genes affected by SOX4 expression were also
      identified, including BCL10, CSF1, and NcoA4/ARA70. TLE-1 and BBC3/PUMA were
      identified as direct targets of SOX4. Silencing of SOX4 by small interfering RNA
      transfection induced apoptosis of prostate cancer cells, suggesting that SOX4
      could be a therapeutic target for prostate cancer. Stable transfection of SOX4
      into nontransformed prostate cells enabled colony formation in soft agar,
      suggesting that, in the proper cellular context, SOX4 can be a transforming
      oncogene.

PMID- 16618721
TI  - Suppression of centrosome amplification after DNA damage depends on p27
      accumulation.
AB  - The centrosome plays a fundamental role in cell division, cell polarity, and cell
      cycle progression. Centrosome duplication is mainly controlled by cyclin
      dependent kinase 2 (CDK2)/cyclin E and cyclin A complexes, which are inhibited by
      the CDK inhibitors p21Cip1 and p27Kip1. It is thought that abnormal activation of
      CDK2 induces centrosome amplification that is frequently observed in a wide range
      of aggressive tumors. We previously reported that overexpression of the oncogene
      MYCN leads to centrosome amplification after DNA damage in neuroblastoma cells.
      We here show that centrosome amplification after gamma-irradiation was caused by
      suppression of p27 expression in MYCN-overexpressing cells. We further show that
      p27-/- and p27+/- mouse embryonic fibroblasts and p27-silenced human cells
      exhibited a significant increase in centrosome amplification after DNA damage.
      Moreover, abnormal mitotic cells with amplified centrosomes were frequently
      observed in p27-silenced cells. In response to DNA damage, the level of p27
      gradually increased in normal cells independently of the ataxia telangiectasia
      mutated/p53 pathway, whereas Skp2, an F-box protein component of an SCF ubiquitin
      ligase complex that targets p27, was reduced. Additionally, p27 levels in MYCN
      overexpressing cells were restored by treatment with Skp2 small interfering RNA,
      indicating that down-regulation of p27 by MYCN was due to high expression of
      Skp2. These results suggest that the accumulation of p27 after DNA damage is
      required for suppression of centrosome amplification, thereby preventing
      chromosomal instability.

PMID- 16618722
TI  - Subtractive transcriptomics: establishing polarity drives in vitro human
      endothelial morphogenesis.
AB  - Although investigations of mature normal and tumor-derived capillaries have
      resulted in characterization of these structures at the phenotypic level, less is
      known regarding the initial molecular cues for cellular assembly of endothelial
      cells into human capillaries. Here, we employ a novel combination of
      microenvironmental manipulation and microarray data filtration over narrowly
      delineated temporal data series to identify the morphogenesis component apart
      from the proliferation component, as pooled human microvascular-derived
      endothelial cells are induced to form capillary-like structures in vitro in a
      murine tumor-derived matrix. The 217 morphogenesis-specific genes identified
      using this subtractive transcriptomics approach are mostly independent of the
      angiogenic proteins currently used as therapeutic targets for aberrant
      angiogenesis. Quantitative real-time PCR was used to validate 20% of these
      transcripts. Immunofluorescent analysis of proliferating and tube-forming cells
      validates at the protein level the morphogenesis-specific expression pattern of
      16 of the 217 gene products identified. The transcripts that are selectively up
      regulated in tube-forming endothelial cells reveal a temporal expression pattern
      of genes primarily associated with intracellular trafficking, guided migration,
      cytoskeletal reorganization, cellular adhesion, and proliferation inhibition.
      These data show that a sequential up-regulation of genes that establish and
      maintain polarity occurs during migration and morphogenesis of in vitro human
      endothelial cells undergoing tubulogenesis; some of which may well be effective
      as novel antiangiogenic drug targets.

PMID- 16618723
TI  - Chronic exposure to lead chromate causes centrosome abnormalities and aneuploidy
      in human lung cells.
AB  - Hexavalent chromium [Cr(VI)] compounds are established human lung carcinogens.
      The carcinogenicity of Cr(VI) is related to its solubility, with the most potent
      carcinogens being the insoluble particulate Cr(VI) compounds. However, it remains
      unknown why particulate Cr(VI) is more carcinogenic than soluble Cr(VI). One
      possible explanation is that particulates may provide more chronic exposures to
      chromate over time. We found that aneuploid cells increased in a concentration-
      and time-dependent manner after chronic exposure to lead chromate. Specifically,
      a 24-hour lead chromate exposure induced no aneugenic effect, whereas a 120-hour
      exposure to 0.5 and 1 microg/cm2 lead chromate induced 55% and 60% aneuploid
      metaphases, respectively. We also found that many of these aneuploid cells were
      able to continue to grow and form colonies. Centrosome defects are known to
      induce aneuploidy; therefore, we investigated the effects of chronic lead
      chromate exposure on centrosomes. We found that centrosome amplification in
      interphase and mitotic cells increased in a concentration- and time-dependent
      manner with 0.5 and 1 microg/cm2 lead chromate for 120 hours, inducing aberrant
      centrosomes in 18% and 21% of interphase cells and 32% and 69% of mitotic cells,
      respectively; however, lead oxide did not induce centrosome amplification in
      interphase or mitotic cells. There was also an increase in aberrant mitosis after
      chronic exposure to lead chromate with the emergence of disorganized anaphase and
      mitotic catastrophe. These data suggest that one possible mechanism for lead
      chromate-induced carcinogenesis is through centrosome dysfunction, leading to the
      induction of aneuploidy.

PMID- 16618724
TI  - Cohypermethylation of p16 and FHIT promoters as a prognostic factor of recurrence
      in surgically resected stage I non-small cell lung cancer.
AB  - Despite advances in the detection and treatment of lung cancer, the prognosis for
      patients with lung cancer is poor, partly as a result of recurrences. We
      retrospectively analyzed the relationship between recurrence and survival in
      patients with non-small cell lung cancers (NSCLC), and the promoter methylation
      of p16, GSTP1, FHIT, H-cadherin, and RARbeta2 genes to identify a prognostic
      molecular marker associated with the recurrence of NSCLC. Methylation status from
      335 paraffin blocks was determined by methylation-specific PCR. Of the 335 NSCLC
      samples, promoter methylation was detected in 35% for p16, 39% for RARbeta2, 42%
      for H-cadherin, 7% for GSTP1, and 21% for FHIT. Recurrence was observed in 39%
      (132 of 335) of the patients. Recurrence was significantly associated with
      histology (P = 0.001) and pathologic stage (P = 0.009). Hypermethylation of any
      single gene was not associated with recurrence in patients. However,
      cohypermethylation of p16 and FHIT genes in stage I NSCLCs was associated with an
      increased risk of recurrence [odds ratio, 6.43; 95% confidence interval (CI),
      1.04-20.19; P = 0.02] and poor recurrence-free survival after surgery (hazard
      ratio, 2.03; 95% CI, 1.09-6.23; P = 0.02). In addition, their survival after
      recurrence was also 4.62 times poorer (95% CI, 1.27-16.48; P = 0.005) than for
      those without cohypermethylation of both genes. In conclusion, the present study
      suggests that cohypermethylation of p16 and FHIT genes in patients with stage I
      NSCLC may be a valuable biomarker for predicting the recurrence-associated
      prognosis of the disease.

PMID- 16618725
TI  - Detection of recurrent copy number loss at Yp11.2 involving TSPY gene cluster in
      prostate cancer using array-based comparative genomic hybridization.
AB  - Prostate cancer is the second leading cause of cancer deaths among American men.
      The loss of Y chromosome has been frequently observed in primary prostate cancer
      as well as other types of cancer. Earlier, we showed that introduction of the
      human Y chromosome suppresses the in vivo tumorigenicity of the prostate cancer
      cell line PC-3. To further characterize the Y chromosome, we have developed a
      high-density bacterial artificial chromosome (BAC) microarray containing 178 BAC
      clones from the human Y chromosome. BAC microarray was used for array comparative
      genomic hybridization on prostate cancer samples and cell lines. The most
      prominent observation on prostate cancer specimens was a deletion at Yp11.2
      containing the TSPY tandem gene array. Out of 36 primary prostate tumors
      analyzed, 16 (44.4%) samples exhibited loss of TSPY gene copies. Notably, we
      observed association between the number of TSPY copies in the blood and the
      incidence of prostate cancer. Moreover, PC-3 hybrids with an intact Yp11.2 did
      not grow tumors in nude mice, whereas PC-3 hybrids with a deletion at Yp11.2 grew
      tumors in nude mice.

PMID- 16618726
TI  - Combined cDNA array comparative genomic hybridization and serial analysis of gene
      expression analysis of breast tumor progression.
AB  - To identify genetic changes involved in the progression of breast carcinoma, we
      did cDNA array comparative genomic hybridization (CGH) on a panel of breast
      tumors, including 10 ductal carcinoma in situ (DCIS), 18 invasive breast
      carcinomas, and two lymph node metastases. We identified 49 minimal commonly
      amplified regions (MCRs) that included known (1q, 8q24, 11q13, 17q21-q23, and
      20q13) and several uncharacterized (12p13 and 16p13) regional copy number gains.
      With the exception of the 17q21 (ERBB2) amplicon, the overall frequency of copy
      number alterations was higher in invasive tumors than that in DCIS, with several
      of them present only in invasive cancer. Amplification of candidate loci was
      confirmed by quantitative PCR in breast carcinomas and cell lines. To identify
      putative targets of amplicons, we developed a method combining array CGH and
      serial analysis of gene expression (SAGE) data to correlate copy number and
      expression levels for each gene within MCRs. Using this approach, we were able to
      distinguish a few candidate targets from a set of coamplified genes. Analysis of
      the 12p13-p12 amplicon identified four putative targets: TEL/ETV6, H2AFJ, EPS8,
      and KRAS2. The amplification of all four candidates was confirmed by quantitative
      PCR and fluorescence in situ hybridization, but only H2AFJ and EPS8 were
      overexpressed in breast tumors with 12p13 amplification compared with a panel of
      normal mammary epithelial cells. These results show the power of combined array
      CGH and SAGE analysis for the identification of candidate amplicon targets and
      identify H2AFJ and EPS8 as novel putative oncogenes in breast cancer.

PMID- 16618727
TI  - Two-dimensional transcriptome profiling: identification of messenger RNA isoform
      signatures in prostate cancer from archived paraffin-embedded cancer specimens.
AB  - The expression of specific mRNA isoforms may uniquely reflect the biological
      state of a cell because it reflects the integrated outcome of both
      transcriptional and posttranscriptional regulation. In this study, we constructed
      a splicing array to examine approximately 1,500 mRNA isoforms from a panel of
      genes previously implicated in prostate cancer and identified a large number of
      cell type-specific mRNA isoforms. We also developed a novel "two-dimensional"
      profiling strategy to simultaneously quantify changes in splicing and transcript
      abundance; the results revealed extensive covariation between transcription and
      splicing in prostate cancer cells. Taking advantage of the ability of our
      technology to analyze RNA from formalin-fixed, paraffin-embedded tissues, we
      derived a specific set of mRNA isoform biomarkers for prostate cancer using
      independent panels of tissue samples for feature selection and cross-analysis. A
      number of cancer-specific splicing switch events were further validated by laser
      capture microdissection. Quantitative changes in transcription/RNA stability and
      qualitative differences in splicing ratio may thus be combined to characterize
      tumorigenic programs and signature mRNA isoforms may serve as unique biomarkers
      for tumor diagnosis and prognosis.

PMID- 16618728
TI  - Targeting oncogenes to improve breast cancer chemotherapy.
AB  - Despite recent advances in treatment, breast cancer remains a serious health
      threat for women. Traditional chemotherapies are limited by a lack of specificity
      for tumor cells and the cell cycle dependence of many chemotherapeutic agents.
      Here we report a novel strategy to help overcome these limitations. Using triplex
      forming oligonucleotides (TFOs) to direct DNA damage site-specifically to
      oncogenes overexpressed in human breast cancer cells, we show that the
      effectiveness of the anticancer nucleoside analogue gemcitabine can be improved
      significantly. TFOs targeted to the promoter region of c-myc directly inhibited
      gene expression by approximately 40%. When used in combination, specific TFOs
      increased the incorporation of gemcitabine at the targeted site approximately 4
      fold, presumably due to induction of replication-independent DNA synthesis. Cells
      treated with TFOs and gemcitabine in combination showed a reduction in both cell
      survival and capacity for anchorage-independent growth (approximately 19% of
      untreated cells). This combination affected the tumorigenic potential of these
      cancer cells to a significantly greater extent than either treatment alone. This
      novel strategy may be used to increase the range of effectiveness of antitumor
      nucleosides in any tumor which overexpresses a targetable oncogene. Multifaceted
      chemotherapeutic approaches such as this, coupled with triplex-directed gene
      targeting, may lead to more than incremental improvements in nonsurgical
      treatment of breast tumors.

PMID- 16618729
TI  - Identification of EZH2 as a molecular marker for a precancerous state in
      morphologically normal breast tissues.
AB  - The discovery of molecular markers to detect the precancerous state would have
      profound implications in the prevention of breast cancer. We report that the
      expression of the Polycomb group protein EZH2 increases in histologically normal
      breast epithelium with higher risk of developing cancer. We identify EZH2 as a
      potential marker for detecting preneoplastic lesions of the breast in vivo and as
      a possible target for preventative intervention.

PMID- 16618730
TI  - Identification of domains of BRCA1 critical for the ubiquitin-dependent
      inhibition of centrosome function.
AB  - The breast and ovarian cancer specific tumor suppressor BRCA1, bound to BARD1,
      has multiple functions aimed at maintaining genomic stability in the cell. We
      have shown earlier that the BRCA1/BARD1 E3 ubiquitin ligase activity regulates
      centrosome-dependent microtubule nucleation. In this study, we tested which
      domains of BRCA1 and BARD1 were required to control the centrosome function. In
      the present study, (a) we confirmed that the ubiquitination activity of BRCA1
      regulates centrosome number and function in Hs578T breast cancer cells; (b) we
      observed that both the amino and carboxyl termini of BRCA1 are required for
      regulation of centrosome function in vitro; (c) an internal domain (770-1,290) is
      dispensable for centrosome regulation; (d) BARD1 is required for regulation of
      centrosome function and protein sequences within the terminal 485 amino acids are
      necessary for activity; and (e) BARD1 is localized at the centrosome throughout
      the cell cycle. We conclude that the BRCA1-dependent E3 ubiquitin ligase
      functions to restrain centrosomes in mammary cells, and loss of BRCA1 in the
      precancerous breast cell leads to centrosomal hypertrophy, a phenotype commonly
      observed in incipient breast cancer.

PMID- 16618731
TI  - Id1 transcription inhibitor-matrix metalloproteinase 9 axis enhances invasiveness
      of the breakpoint cluster region/abelson tyrosine kinase-transformed leukemia
      cells.
AB  - Breakpoint cluster region/Abelson (BCR/ABL) tyrosine kinase enhances the ability
      of leukemia cells to infiltrate various organs. We show here that expression of
      the helix-loop-helix transcription factor Id1 is enhanced by BCR/ABL in a signal
      transducer and activator of transcription 5 (STAT5)-dependent manner. Enhanced
      expression of Id1 plays a key role in BCR/ABL-mediated cell invasion. Down
      regulation of Id1 in BCR/ABL leukemia cells by the antisense cDNA significantly
      reduced their invasive capability through the Matrigel membrane and their ability
      to infiltrate hematopoietic and nonhematopoietic organs resulting in delayed
      leukemogenesis in mice. The Id1-promoted cell invasiveness was seemingly mediated
      by matrix metalloproteinase 9 (MMP9). Transactivation of MMP9 promoter in BCR/ABL
      cells was dependent on Id1 and abrogation of the MMP9 catalytic activity by a
      metalloproteinase inhibitor or blocking antibody decreased invasive capacity of
      leukemia cells. These data suggest that BCR/ABL-STAT5-Id1-MMP9 pathway may play a
      critical role in BCR/ABL-mediated leukemogenesis by enhancing invasiveness of
      leukemia cells.

PMID- 16618732
TI  - Differential functional activation of chemokine receptor CXCR4 is mediated by G
      proteins in breast cancer cells.
AB  - CXCR4 is a G protein-coupled receptor of considerable biological significance,
      and among its numerous functions, it is suggested to play a critical role in
      cancer metastasis. We have investigated the expression and function of CXCR4 in a
      range of breast cancer cell lines covering a spectrum of invasive phenotypes and
      found that, while surface levels of CXCR4 were uniform across the entire panel,
      only highly invasive cells that are metastatic in immunocompromised mice
      expressed functional receptors. CXCL12/SDF-1 induced cellular responses such as
      calcium mobilization, actin polymerization, and chemotaxis in metastatic cells,
      whereas noninvasive cells were unresponsive. Moreover, CXCL12 activated multiple
      signaling pathways downstream of G proteins in highly invasive cells but failed
      to activate any of the examined kinase cascades in noninvasive cell lines. This
      blockade in nonmetastatic cell lines seems to be due to the inability of G
      protein alpha and beta subunits to form a heterotrimeric complex with CXCR4.
      Galpha and Gbeta were able to bind to CXCR4 independently in all cell lines, but
      the association of G protein alphabetagamma heterotrimers with the receptor, a
      prerequisite for signal transduction downstream from G protein-coupled receptors,
      was only observed in the highly invasive cell lines. Our findings show, for the
      first time, that CXCR4 function is subject to complex and potentially tightly
      controlled regulation in breast cancer cells via differential G protein-receptor
      complex formation, and this regulation may play a role in the transition from
      nonmetastatic to malignant tumors.

PMID- 16618733
TI  - Growth-regulated oncogene is pivotal in thrombin-induced angiogenesis.
AB  - The mechanism of thrombin-induced angiogenesis is poorly understood. Using a gene
      chip array to investigate the pro-malignant phenotype of thrombin-stimulated
      cells, we observed that thrombin markedly up-regulates growth-regulated oncogene
      alpha (GRO-alpha) in several tumor cell lines as well as endothelial cells by
      mRNA and protein analysis. Thrombin enhanced the secretion of GRO-alpha from
      tumor cells 25- to 64-fold. GRO-alpha is a CXC chemokine with tumor-associated
      angiogenic as well as oncogenic activation following ligation of its CXCR2
      receptor. GRO-alpha enhanced angiogenesis in the chick chorioallantoic membrane
      assay 2.2-fold, providing direct evidence for GRO-alpha as an angiogenic growth
      factor. Anti-GRO-alpha antibody completely inhibited the 2.7-fold thrombin
      induced up-regulation of angiogenesis, as well as the 1.5-fold thrombin-induced
      up-regulation of both endothelial cell cord formation in Matrigel and growth in
      vitro. Thrombin as well as its PAR-1 receptor activation peptide [thrombin
      receptor activation peptide (TRAP)] as well as GRO-alpha all markedly increased
      vascular regulatory proteins and growth factors: matrix metalloproteinase (MMP)
      1, MMP-2, vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2),
      CD31, and receptors KDR and CXCR2 in human umbilical vein endothelial cells. All
      of the thrombin/TRAP gene up-regulations were completely inhibited by anti-GRO
      alpha antibody and unaffected by irrelevant antibody. Similar inhibition of gene
      up-regulation as well as thrombin-induced chemotaxis was noted with small
      interfering RNA (shRNA) GRO-alpha KD 4T1 breast tumor and B16F10 melanoma cells.
      In vivo tumor growth studies in wild-type mice with shRNA GRO-alpha KD cells
      revealed 2- to 4-fold impaired tumor growth, metastasis, and angiogenesis, which
      was not affected by endogenous thrombin. Thus, thrombin-induced angiogenesis
      requires the up-regulation of GRO-alpha. Thrombin up-regulation of GRO-alpha in
      tumor cells as well as endothelial cells contributes to tumor angiogenesis.

PMID- 16618734
TI  - High-throughput loss-of-heterozygosity study of chromosome 3p in lung cancer
      using single-nucleotide polymorphism markers.
AB  - Loss of DNA copy number at the short arm of chromosome 3 is one of the most
      common genetic changes in human lung cancer, suggesting the existence of one or
      more tumor suppressor genes (TSG) at 3p. To identify most frequently deleted
      regions and candidate TSGs within these regions, a recently developed single
      nucleotide polymorphism (SNP)-mass spectrometry-genotyping (SMSG) technology was
      applied to investigate the loss of heterozygosity (LOH) in 30 primary non-small
      cell lung cancers. A total of 386 SNP markers that spanned a region of 70 Mb at
      3p, from 3pter to 3p14.1, were selected for LOH analysis. The average intermarker
      distance in the present study is approximately 180 kb. Several frequently deleted
      regions, including 3p26.3, 3p25.3, 3p24.1, 3p23, and 3p21.1, were found. Several
      candidate TSGs within these frequently detected LOH regions have been found,
      including APG7L at 3p25.3, CLASP2 at 3p23, and CACNA2D3 at 3p21.1. This study
      also showed that SMSG technology is a very useful approach to rapidly define the
      minimal deleted region and to identify target TSGs in a given cancer.

PMID- 16618735
TI  - Related to testes-specific, vespid, and pathogenesis protein-1 (RTVP-1) is
      overexpressed in gliomas and regulates the growth, survival, and invasion of
      glioma cells.
AB  - In this study, we examined the expression and functions of related to testes
      specific, vespid, and pathogenesis protein 1 (RTVP-1) in glioma cells. RTVP-1 was
      expressed in high levels in glioblastomas, whereas its expression in low-grade
      astrocytomas and normal brains was very low. Transfection of glioma cells with
      small interfering RNAs targeting RTVP-1 decreased cell proliferation in all the
      cell lines examined and induced cell apoptosis in some of them. Overexpression of
      RTVP-1 increased astrocyte and glioma cell proliferation and the anchorage
      independent growth of the cells. In addition, overexpression of RTVP-1 rendered
      glioma cells more resistant to the apoptotic effect of tumor necrosis factor
      related apoptosis-inducing ligand and serum deprivation. To delineate the
      molecular mechanisms involved in the survival effects of RTVP-1, we examined the
      expression and phosphorylation of various apoptosis-related proteins. We found
      that overexpression of RTVP-1 decreased the phosphorylation of c-Jun-NH2-kinase
      and increased the expression of Bcl2 and that the protective effect of RTVP-1 was
      partially mediated by Bcl2. Finally, we found that RTVP-1 regulated the invasion
      of glioma cells as was evident by their enhanced migration through Matrigel and
      by their increased invasion in a spheroid confrontation assay. The increased
      invasive potential of the RTVP-1 overexpressors was also shown by the increased
      activity of matrix metalloproteinase 2 in these cells. Our results suggest that
      the expression of RTVP-1 is correlated with the degree of malignancy of
      astrocytic tumors and that RTVP-1 is involved in the regulation of the growth,
      survival, and invasion of glioma cells. Collectively, these findings suggest that
      RTVP-1 is a potential therapeutic target in gliomas.

PMID- 16618736
TI  - The kinase Mirk/Dyrk1B mediates cell survival in pancreatic ductal
      adenocarcinoma.
AB  - Ductal adenocarcinoma of the pancreas is almost uniformly lethal as this cancer
      is invariably detected at an advanced stage and is resistant to treatment. The
      serine/threonine kinase Mirk/Dyrk1B has been shown to be antiapoptotic in
      rhabdomyosarcomas. We have now investigated whether Mirk might mediate survival
      in another cancer in which Mirk is widely expressed, pancreatic ductal
      adenocarcinoma. Mirk was an active kinase in each pancreatic cancer cell line
      where it was detected. Mirk knockdown by RNA interference (RNAi) reduced the
      clonogenicity of Panc1 pancreatic cancer cells 4-fold and decreased tumor cell
      number, showing that Mirk mediates survival in these cells. Mirk knockdown by
      synthetic duplex RNAis in Panc1, AsPc1, and SU86.86 pancreatic cancer cells
      induced apoptosis and enhanced the apoptosis induced by gemcitibine. Mirk
      knockdown did not increase the abundance or activation of Akt. However, four of
      five pancreatic carcinoma cell lines exhibited either elevated Mirk activity or
      elevated Akt activity, suggesting that pancreatic cancer cells primarily rely on
      Mirk or Akt for survival signaling. Mirk protein was detected by
      immunohistochemistry in 25 of 28 cases (89%) of pancreatic ductal adenocarcinoma,
      with elevated expression in 11 cases (39%). Increased expression of Mirk was seen
      in pancreatic carcinomas compared with primary cultures of normal ductal
      epithelium by serial analysis of gene expression and by immunohistochemistry.
      Thus, Mirk is a survival factor for pancreatic ductal adenocarcinoma. Because
      knockout of Mirk does not cause embryonic lethality, Mirk is not essential for
      normal cell growth and may represent a novel therapeutic target.

PMID- 16618737
TI  - Noninvasive magnetic resonance imaging of transport and interstitial fluid
      pressure in ectopic human lung tumors.
AB  - Tumor response to blood borne drugs is critically dependent on the efficiency of
      vascular delivery and transcapillary transfer. However, increased tumor
      interstitial fluid pressure (IFP) forms a barrier to transcapillary transfer,
      leading to resistance to drug delivery. We present here a new, noninvasive method
      which estimates IFP and its spatial distribution in vivo using contrast-enhanced
      magnetic resonance imaging (MRI). This method was tested in ectopic human non
      small-cell lung cancer which exhibited a high IFP of approximately 28 mm Hg and,
      for comparison, in orthotopic MCF7 human breast tumors which exhibited a lower
      IFP of approximately 14 mm Hg, both implanted in nude mice. The MRI protocol
      consisted of slow infusion of the contrast agent [gadolinium
      diethylenetriaminepentaacetic acid (GdDTPA)] into the blood for approximately 2
      hours, sequential acquisition of images before and during the infusion, and
      measurements of T1 relaxation rates before infusion and after blood and tumor
      GdDTPA concentration reached a steady state. Image analysis yielded parametric
      images of steady-state tissue GdDTPA concentration with high values of this
      concentration outside the tumor boundaries, approximately 1 mmol/L, declining in
      the tumor periphery to approximately 0.5 mmol/L, and then steeply decreasing to
      low or null values. The distribution of steady-state tissue GdDTPA concentration
      reflected the distribution of IFP, showing an increase from the rim inward, with
      a high IFP plateau inside the tumor. The changes outside the borders of the
      tumors with high IFP were indicative of convective transport through the
      interstitium. This work presents a noninvasive method for assessing the spatial
      distribution of tumor IFP and mapping barriers to drug delivery and transport.

PMID- 16618738
TI  - Hemangioblastomas share protein expression with embryonal hemangioblast
      progenitor cell.
AB  - Hemangioblastomas are central nervous system (CNS) tumors of unknown
      histogenesis, which can occur sporadically or in von Hippel-Lindau disease.
      Hemangioblastomas are composed of neoplastic "stromal" cells of unknown origin,
      accompanied by intensive reactive angiogenesis. Failure to specify the cytologic
      origin of the stromal cell has precluded the development of nonsurgical therapies
      and limits understanding of its basic biology. We report that the stromal cells
      express proteins (Scl, brachyury, Csf-1R, Gata-1, Flk-1, and Tie-2) that
      characterize embryonic progenitor cells with hemangioblastic differentiation
      potential and conclude that embryonic progenitors with hemangioblast potential
      represent a possible cytologic equivalent of the stromal cell. We also identified
      a new autocrine/paracrine stimulatory loop between the receptor Tie-2 and the
      hypoxia-inducible factor target Ang-1, which, combined with previous
      observations, suggests that a variety of autocrine loops may be initiated in
      hemangioblastomas, depending on the differentiation status of the tumor cells and
      the extent of HIF downstream activation. Finally, the consistent identification
      of Scl in the stromal cells may help explain the unique and characteristic
      topographical distribution of hemangioblastomas within the CNS.

PMID- 16618739
TI  - Maspin retards cell detachment via a novel interaction with the urokinase-type
      plasminogen activator/urokinase-type plasminogen activator receptor system.
AB  - It is well documented that tumor suppressive maspin inhibits tumor cell invasion
      and extracellular matrix remodeling. Maspin is a cytosolic, cell surface
      associated, and secreted protein in the serine protease inhibitor superfamily.
      Although several molecules have been identified as candidate intracellular maspin
      targets, the extracellular maspin target(s) remains elusive. Although maspin does
      not directly inhibit urokinase-type plasminogen activator (uPA) activity, we have
      shown evidence that maspin may block the pericellular proteolysis mediated by
      cell surface-associated uPA. In the current study, maspin significantly inhibited
      the Ca2+ reduction-induced detachment of DU145 cells. This maspin effect was
      associated with increased and sustained levels of mature focal adhesion contacts
      (FAC). We noted that maspin (a) colocalized with uPA and uPA receptor (uPAR), (b)
      enhanced the interaction between uPAR and low-density lipoprotein receptor
      related protein, and (c) induced rapid internalization of uPA and uPAR. The
      maspin effects on surface-associated uPA and uPAR required the interaction
      between uPA and uPAR. Further biochemical and biophysical analyses revealed that
      maspin specifically bound to pro-uPA with a deduced K(d) of 270 nmol/L and
      inhibited the plasmin-mediated pro-uPA cleavage. Interestingly, substitution of
      maspin p1' site Arg340 in the reactive site loop (RSL) with alanine not only
      abolished the binding to pro-uPA but also diminished the maspin effects on pro
      uPA cleavage and cell detachment. These data show an important role of maspin RSL
      in regulating the uPA/uPAR-dependent cell detachment. Together, our data led to a
      new hypothesis that maspin may stabilize mature FACs by quenching localized
      uPA/uPAR complex before uPA activation.

PMID- 16618740
TI  - Notch1 signaling promotes primary melanoma progression by activating mitogen
      activated protein kinase/phosphatidylinositol 3-kinase-Akt pathways and up
      regulating N-cadherin expression.
AB  - Cellular signaling mediated by Notch receptors results in coordinated regulation
      of cell growth, survival, and differentiation. Aberrant Notch activation has been
      linked to a variety of human neoplasms. Here, we show that Notch1 signaling
      drives the vertical growth phase (VGP) of primary melanoma toward a more
      aggressive phenotype. Constitutive activation of Notch1 by ectopic expression of
      the Notch1 intracellular domain enables VGP primary melanoma cell lines to
      proliferate in a serum-independent and growth factor-independent manner in vitro
      and to grow more aggressively with metastatic activity in vivo. Notch1 activation
      also enhances tumor cell survival when cultured as three-dimensional spheroids.
      Such effects of Notch signaling are mediated by activation of the mitogen
      activated protein kinase (MAPK) and Akt pathways. Both pathways are activated in
      melanoma cells following Notch1 pathway activation. Inhibition of either the MAPK
      or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway reverses the Notch1
      signaling-induced tumor cell growth. Moreover, the growth-promoting effect of
      Notch1 depends on mastermind-like 1. We further showed that Notch1 activation
      increases tumor cell adhesion and up-regulates N-cadherin expression. Our data
      show regulation of MAPK/PI3K-Akt pathway activities and expression of N-cadherin
      by the Notch pathway and provide a mechanistic basis for Notch signaling in the
      promotion of primary melanoma progression.

PMID- 16618741
TI  - Heat shock protein 70 neutralization exerts potent antitumor effects in animal
      models of colon cancer and melanoma.
AB  - When overexpressed, the stress protein heat shock protein 70 (HSP70) increases
      the oncogenic potential of cancer cells in rodent models. HSP70 also prevents
      apoptosis, thereby increasing the survival of cells exposed to a wide range of
      otherwise lethal stimuli. These protective functions of HSP70 involve its
      interaction with and neutralization of the adaptor molecule apoptotic protease
      activation factor-1, implicated in caspase activation, and the flavoprotein
      apoptosis-inducing factor (AIF), involved in caspase-independent cell death. We
      have shown previously that a peptide containing the AIF sequence involved in its
      interaction with HSP70 (ADD70, amino acids 150-228) binds to and neutralizes
      HSP70 in the cytosol, thereby sensitizing cancer cells to apoptosis induced by a
      variety of death stimuli. Here, we show that expression of ADD70 in tumor cells
      decreases their tumorigenicity in syngeneic animals without affecting their
      growth in immunodeficient animals. ADD70 antitumorigenic effects are associated
      with an increase in tumor-infiltrating cytotoxic CD8+ T cells. In addition, ADD70
      sensitizes rat colon cancer cells (PROb) and mouse melanoma cells (B16F10) to the
      chemotherapeutic agent cisplatin. ADD70 also shows an additive effect with HSP90
      inhibition by 17-allylamino-17-demethoxygeldanamycin in vitro. Altogether, these
      data indicate the potential interest of targeting the HSP70 interaction with AIF
      for cancer therapy.

PMID- 16618742
TI  - High expression of ligands for chemokine receptor CXCR2 in alveolar epithelial
      neoplasia induced by oncogenic kras.
AB  - CXCL8, a ligand for the chemokine receptor CXCR2, was recently reported to be a
      transcriptional target of Ras signaling, but its role in Ras-induced
      tumorigenesis has not been fully defined. Here, we investigated the role of KC
      and MIP-2, the murine homologues of CXCL8, in Kras(LA1) mice, which develop lung
      adenocarcinoma owing to somatic activation of the KRAS oncogene. We first
      investigated biological evidence of CXCR2 ligands in Kras(LA1) mice. Malignant
      progression of normal alveolar epithelial cells to adenocarcinoma in Kras(LA1)
      mice was associated with enhanced intralesional vascularity and neutrophilic
      inflammation, which are hallmarks of chemoattraction by CXCR2 ligands. In in
      vitro migration assays, supernatants of bronchoalveolar lavage samples from
      Kras(LA1) mice chemoattracted murine endothelial cells, alveolar inflammatory
      cells, and the LKR-13 lung adenocarcinoma cell line derived from Kras(LA1) mice,
      an effect that was abrogated by pretreatment of the cells with a CXCR2
      neutralizing antibody. CXCR2 and its ligands were highly expressed in LKR-13
      cells and premalignant alveolar lesions in Kras(LA1) mice. Treatment of Kras(LA1)
      mice with a CXCR2-neutralizing antibody inhibited the progression of premalignant
      alveolar lesions and induced apoptosis of vascular endothelial cells within
      alveolar lesions. Whereas the proliferation of LKR-13 cells in vitro was
      resistant to treatment with the antibody, LKR-13 cells established as syngeneic
      tumors were sensitive, supporting a role for the tumor microenvironment in the
      activity of CXCR2. Thus, high expression of CXCR2 ligands may contribute to the
      expansion of early alveolar neoplastic lesions induced by oncogenic KRAS.

PMID- 16618743
TI  - Development of real-time subcellular dynamic multicolor imaging of cancer-cell
      trafficking in live mice with a variable-magnification whole-mouse imaging
      system.
AB  - With the use of dual-color fluorescent cells and a highly sensitive whole-mouse
      imaging system with both macro-optics and micro-optics, we report here the
      development of subcellular real-time imaging of cancer cell trafficking in live
      mice. To observe cytoplasmic and nuclear dynamics in the living mouse, tumor
      cells were labeled in the nucleus with green fluorescent protein and with red
      fluorescent protein in the cytoplasm. Dual-color cancer cells were injected by a
      vascular route in an abdominal skin flap in nude mice. The mice were imaged with
      an Olympus OV100 whole-mouse imaging system with a sensitive CCD camera and five
      objective lenses, parcentered and parfocal, enabling imaging from macrocellular
      to subcellular. We observed the nuclear and cytoplasmic behavior of cancer cells
      in real time in blood vessels as they moved by various means or adhered to the
      vessel surface in the abdominal skin flap. During extravasation, real-time dual
      color imaging showed that cytoplasmic processes of the cancer cells exited the
      vessels first, with nuclei following along the cytoplasmic projections. Both
      cytoplasm and nuclei underwent deformation during extravasation. Different cancer
      cell lines seemed to strongly vary in their ability to extravasate. With the dual
      color cancer cells and the highly sensitive whole-mouse imaging system described
      here, the subcellular dynamics of cancer metastasis can now be observed in live
      mice in real time. This imaging technology will enable further understanding of
      the critical steps of metastasis and provide visible targets for antimetastasis
      drug development.

PMID- 16618744
TI  - Shh pathway activity is down-regulated in cultured medulloblastoma cells:
      implications for preclinical studies.
AB  - Gene expression profiling indicates that the Sonic Hedgehog (Shh) pathway is
      active in approximately 30% of human medulloblastomas, suggesting that it could
      provide a useful therapeutic target. Previously, we showed that spontaneous
      medulloblastomas in Ptc1(+/-)p53-/- mice could be eradicated by treatment with a
      small-molecule inhibitor (HhAntag) of Smoothened (Smo). Here, we compared the
      responses of mouse medulloblastoma cells propagated in flank allografts, either
      directly or after culture in vitro, to HhAntag. We found that Shh pathway
      activity was suppressed in medulloblastoma cells cultured in vitro and it was not
      restored when these cells were transplanted into the flank of nude mice. The
      growth of these transplanted tumor cells was not inhibited by treatment of mice
      with doses of HhAntag that completely suppressed Smo activity. Interestingly,
      tumor cells transplanted directly into the flank maintained Smo activity and were
      sensitive to treatment with HhAntag. These findings indicate that propagation of
      tumor cells in culture inhibits Smo activity in a way that cannot be reversed by
      transplantation in vivo, and they raise concerns about the use of cultured tumor
      cells to test the efficacy of Shh pathway inhibitors as anticancer therapies.

PMID- 16618745
TI  - Radiation-induced caspase-8 mediates p53-independent apoptosis in glioma cells.
AB  - Malignant gliomas are almost uniformly fatal and display exquisite radiation
      resistance. Glioma cells lacking wild-type (WT) p53 function are more susceptible
      to radiation-induced apoptosis than their isogenic counterparts expressing WT
      p53. We explored the mechanisms of such apoptosis and found that, in the absence
      of WT p53, radiation increases caspase-8 expression and activity. Inhibition of
      caspase-8 expression using caspase-8 antisense or small interfering RNA (siRNA)
      oligonucleotides partially blocks radiation-induced apoptosis. In contrast,
      inhibition of the mitochondrial death pathway by expression of Bcl-2 has no
      effect on radiation-induced caspase-8 activity or apoptosis. Our data indicate
      that, in contrast to commonly accepted models of p53-dependent radiation-induced
      apoptosis, in our cell system, radiation relies on caspase-8 activity to help
      mediate p53-independent cell death. In a system of inducible E2F1 activity, E2F1
      activated caspase-8 and, accordingly, decreased cellular viability, effects that
      were abolished by caspase-8 siRNA. In this model, in the absence of WT p53,
      p21Cip1 is not induced, and E2F1 activity is sustained and allows transcription
      and activation of caspase-8. This model may explain why p53 mutations in adult
      gliomas paradoxically correlate with improved survival and enhanced response to
      radiation.

PMID- 16618746
TI  - Transformation of late passage insulin-like growth factor-I receptor null mouse
      embryo fibroblasts by SV40 T antigen.
AB  - There is evidence that the insulin-like growth factor-I (IGF-I) receptor is
      required for transformation by a variety of viral and cellular oncogenes in a
      mouse embryo fibroblast model. To further investigate the IGF-I receptor
      signaling pathways that are required for the permissive effect of the receptor on
      transformation by SV40 T antigen, we established three independent fibroblast
      cell lines each from wild-type and IGF-I receptor null embryos (R-). We
      transfected the wild-type and R- cell lines with an SV40 T antigen plasmid and
      selected three clones from each cell line that expressed T antigen. As in
      previous reports, none of the cloned R- cell lines expressing T antigen were
      transformed as measured by the ability to form large colonies in soft agar.
      However, with further passage, all three T antigen-expressing clones from one of
      the R- cell lines (R(-)3) formed large colonies in soft agar and the
      transformation of these T antigen-expressing clones was confirmed by
      tumorigenesis experiments in immunodeficient mice. DNA microarray analysis
      comparing gene expression between early passage and late passage R(-)3/T antigen
      clones showed, among other changes, an increase in the expression of ErbB-3 mRNA
      in the late passage clones. Also, the expression of ErbB-3 protein was
      dramatically increased in the late passage R(-)3/T antigen clones. We conclude
      that late passage IGF-I receptor null mouse embryo fibroblasts can be transformed
      by SV40 T antigen, and that ErbB-3 may play a role in permitting transformation
      by T antigen.

PMID- 16618747
TI  - Retinoic acid induces p27Kip1 nuclear accumulation by modulating its
      phosphorylation.
AB  - All-trans-retinoic acid (ATRA), the most biologically active metabolite of
      vitamin A, controls cell proliferation, apoptosis, and differentiation depending
      on the cellular context. These activities point to ATRA as a candidate for cancer
      therapy. A pivotal effect of the molecule is the modulation of p27Kip1, a cyclin
      dependent kinase (CDK) inhibitor (CDKI). Here, we investigate the mechanisms by
      which ATRA regulates p27Kip1 level in LAN-5, a neuroblastoma cell line. When
      added to the cells, ATRA causes a rapid nuclear increase of p27Kip1, which
      clearly precedes growth arrest. The early buildup is not due to impairment of the
      CDKI degradation, in contrast to previous observations. Particularly, we did not
      detect the down-regulation of Skp2 and Cks1, two proteins involved in the nuclear
      ubiquitin-dependent p27Kip1 removal. Moreover, the morphogen does not impair the
      CDKI nuclear export and does not cause CDK2 relocalization. The characterization
      of CDKI isoforms by two-dimensional PAGE/immunoblotting showed that ATRA induces
      an early nuclear up-regulation of monophosphorylated p27Kip1. Immunologic studies
      established that this isoform corresponds to p27Kip1 phosphorylated on S10. The
      buildup of phospho(S10)p27Kip1 precedes the CDKI accumulation and increases its
      half-life. Finally, ATRA-treated nuclear LAN-5 extracts showed an enhanced
      capability of phosphorylating p27Kip1 on S10, thus explaining the nuclear up
      regulation of the isoform. In conclusion, our data suggest a novel mechanism of
      ATRA antiproliferative activity, in which the morphogen rapidly up-regulates a
      nuclear kinase activity that phosphorylates p27Kip1 on S10. In turn, this event
      causes the stabilization of p27Kip1 and its accumulation in the nuclear
      compartment.

PMID- 16618748
TI  - Brain-derived neurotrophic factor activation of TrkB induces vascular endothelial
      growth factor expression via hypoxia-inducible factor-1alpha in neuroblastoma
      cells.
AB  - The extent of angiogenesis and/or vascular endothelial growth factor (VEGF)
      expression in neuroblastoma tumors correlates with metastases, N-myc
      amplification, and poor clinical outcome. Recently, we have shown that insulin
      like growth factor-I and serum-derived growth factors stimulate VEGF expression
      in neuroblastoma cells via induction of hypoxia-inducible factor-1alpha (HIF
      1alpha). Because another marker of poor prognosis in neuroblastoma tumors is high
      expression of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase
      receptor, TrkB, we sought to evaluate the involvement of BDNF and TrkB in the
      regulation of VEGF expression. VEGF mRNA levels in neuroblastoma cells cultured
      in serum-free media increased after 8 to 16 hours in BDNF. BDNF induced increases
      in VEGF and HIF-1alpha protein, whereas HIF-1beta levels were unaffected. BDNF
      induced a 2- to 4-fold increase in VEGF promoter activity, which could be
      abrogated if the hypoxia response element in the VEGF promoter was mutated.
      Transfection of HIF-1alpha small interfering RNA blocked BDNF-stimulated
      increases in VEGF promoter activity and VEGF protein expression. The BDNF
      stimulated increases in HIF-1alpha and VEGF expression required TrkB tyrosine
      kinase activity and were completely blocked by inhibitors of phosphatidylinositol
      3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathways. These data
      indicate that BDNF plays a role in regulating VEGF levels in neuroblastoma cells
      and that targeted therapies to BDNF/TrkB, PI3K, mTOR signal transduction
      pathways, and/or HIF-1alpha have the potential to inhibit VEGF expression and
      limit neuroblastoma tumor growth.

PMID- 16618749
TI  - Repression of cap-dependent translation attenuates the transformed phenotype in
      non-small cell lung cancer both in vitro and in vivo.
AB  - Aberrant hyperactivation of the cap-dependent protein synthesis apparatus has
      been documented in a wide range of solid tumors, including epithelial carcinomas,
      but causal linkage has only been established in breast carcinoma. In this report,
      we sought to determine if targeted disruption of deregulated cap-dependent
      translation abrogates tumorigenicity and enhances cell death in non-small cell
      lung cancer (NSCLC). NSCLC cell lines were stably transfected with either wild
      type 4E-BP1 (HA-4E-BP1) or the dominant-active mutant 4E-BP1(A37/A46) (HA-TTAA).
      Transfected NSCLC cells with enhanced translational repression showed pronounced
      cell death following treatment with gemcitabine. In addition, transfected HA-TTAA
      and HA-4E-BP1wt proteins suppressed growth in a cloning efficiency assay. NSCLC
      cells transduced with HA-TTAA also show decreased tumorigenicity in xenograft
      models. Xenograft tumors expressing HA-TTAA were significantly smaller than
      control tumors. This work shows that hyperactivation of the translational
      machinery is necessary for maintenance of the malignant phenotype in NSCLC,
      identifies the molecular strategy used to activate translation, and supports the
      development of lung cancer therapies that directly target the cap-dependent
      translation initiation complex.

PMID- 16618750
TI  - Altered expression of c-IAP1, survivin, and Smac contributes to chemotherapy
      resistance in thyroid cancer cells.
AB  - Resistance to chemotherapy predicts an unfavorable outcome for patients with
      radioiodine-insensitive thyroid cancer. To investigate the mechanisms underlying
      this resistance, we evaluated the expression of four different inhibitor of
      apoptosis proteins, and their antagonist, Smac, in thyroid cancer cells that
      survived 48 hours of exposure to cisplatin, doxorubicin, or taxol. We found high
      levels of c-IAP1 after cisplatin treatment and increased expression of survivin
      following exposure to doxorubicin. Cells that endured treatment with taxol showed
      reduced expression of Smac and released minimal amounts of this protein from the
      mitochondria. Down-regulation of c-IAP1 and survivin increased the cytotoxicity
      of cisplatin and doxorubicin, whereas overexpression of Smac improved the
      efficacy of taxol. Finally, thyroid cancer cells permanently resistant to
      doxorubicin or cisplatin showed increased expression of c-IAP1 and survivin,
      respectively. However, silencing of these proteins by RNA interference restored
      sensitivity to doxorubicin and cisplatin. Thus, in thyroid cancer cells, early
      resistance to chemotherapeutic agents requires high levels of c-IAP1 and survivin
      and low levels of Smac. Furthermore, increased expression of c-IAP1 and survivin
      contributes to the acquisition of permanent resistance to cytotoxic compounds.

PMID- 16618751
TI  - Caspase-8 promotes cell motility and calpain activity under nonapoptotic
      conditions.
AB  - Significant caspase-8 activity has been found in normal and certain tumor cells,
      suggesting that caspase-8 possesses an alternative, nonapoptotic function that
      may contribute to tumor progression. In this article, we report that caspase-8
      promotes cell motility. In particular, caspase-8 is required for the optimal
      activation of calpains, Rac, and lamellipodial assembly. This represents a novel
      nonapoptotic function of caspase-8 acting at the intersection of the caspase-8
      and calpain proteolytic pathways to coordinate cell death versus cell motility
      signaling.

PMID- 16618752
TI  - Down-regulation of CXCL5 inhibits squamous carcinogenesis.
AB  - We report a novel role for the CXC-chemokine, CXCL5, in the proliferation and
      invasion of head and neck squamous cell carcinoma (HNSCC). Previously, we
      reported transcriptional up-regulation of CXCL5 in metastatic cells. In this
      study, we provide biological validation of these findings and show that CXCL5 is
      intimately involved in tumor cell proliferation, migration, and invasion. Cells
      derived from a lymph node metastasis, but not from a synchronous primary tumor,
      secreted CXCL5 as judged by Western blotting of conditioned media. We used RNA
      interference to generate cell lines (shL5) in which CXCL5 expression was greatly
      reduced, and tested whether this modulated the cell phenotype. shL5 cells showed
      decreased proliferation compared with cells harboring nontargeting control
      sequences. In addition, we found that the ability of shL5 cells to migrate and
      invade in vitro through a basement membrane substitute was greatly impaired
      compared with control cells. Finally, whereas control cells were highly
      tumorigenic in nude mice, the tumorigenic potential in vivo of shL5 cells was
      found to be ablated. Taken together, these data suggest that CXCL5 production
      contributes to both enhanced proliferation and invasion of squamous cell
      carcinomas and that targeting of chemokine pathways may represent a potential
      therapeutic modality for these lesions.

PMID- 16618753
TI  - Bone morphogenetic protein 7 protects prostate cancer cells from stress-induced
      apoptosis via both Smad and c-Jun NH2-terminal kinase pathways.
AB  - We reported earlier that exposure to exogenous bone morphogenetic protein 7
      (BMP7) could strongly inhibit serum starvation-induced apoptosis to C4-2B cell
      line, a variant of the LNCaP human prostate cancer cell line with propensity for
      bone metastasis. Whereas serum starvation suppressed the expression of survivin,
      a member of the inhibitor of apoptosis protein family, its expression was
      sustained in the presence of BMP7. In this study, we present evidence that BMP7
      exposure up-regulated survivin promoter activity, an effect that was associated
      with activation of Smad, and could be repressed by dominant-negative Smad5.
      Additionally, serum starvation-induced suppression of c-jun NH2-terminal kinase
      (JNK) activity in C4-2B cells could be mostly restored by BMP7, and a JNK
      inhibitor could counteract the antiapoptotic effect of BMP7, without a
      significant effect on the level of survivin expression. Thus, we identified JNK
      pathway as another signaling mode for the antiapoptotic function of BMP7. To test
      the effect of endogenous up-regulation of BMP7, we genetically modulated the C4
      2B cell line to overexpress BMP7 protein. Not only was this altered cell line
      resistant to serum starvation-induced apoptosis but it also exhibited patterns of
      Smad activation, survivin up-regulation, and JNK activation similar to those of
      the parental C4-2B cells exposed to exogenous BMP7. Consistent with these in
      vitro findings of BMP7 action, we acquired correlative results of Smad
      activation, survivin expression, and JNK activation in the progression of
      prostate cancer in the conditional Pten deletion mouse model, in which we first
      obtained the evidence of BMP7 overexpression.

PMID- 16618754
TI  - Complete elimination of colorectal tumor xenograft by combined manganese
      superoxide dismutase with tumor necrosis factor-related apoptosis-inducing ligand
      gene virotherapy.
AB  - Manganese superoxide dismutase (MnSOD) is a latent tumor suppressor gene. To
      investigate the therapeutic effect of MnSOD and its mechanisms, a replication
      competent recombinant adenovirus with E1B 55-kDa gene deletion (ZD55) was
      constructed, and human MnSOD and tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) genes were inserted to form ZD55-MnSOD and ZD55-TRAIL. ZD55-MnSOD
      exhibited an inhibition in tumor cell growth approximately 1,000-fold greater
      than Ad-MnSOD. ZD55-TRAIL was shown to induce the MnSOD expression in SW620
      cells. Accordingly, by the combined use of ZD55-MnSOD with ZD55-TRAIL (i.e.,
      "dual gene virotherapy"), all established colorectal tumor xenografts were
      completely eliminated in nude mice. The evidence exists that the MnSOD
      overexpression led to a slower tumor cell growth both in vitro and in vivo as a
      result of apoptosis caused by MnSOD and TRAIL overexpression after adenoviral
      transduction. Our results showed that the production of hydrogen peroxide derived
      from MnSOD dismutation activated caspase-8, which might down-regulate Bcl-2
      expression and induce Bax translocation to mitochondria. Subsequently, Bax
      translocation enhanced the release of apoptosis-initiating factor and cytochrome
      c. Cytochrome c finally triggered apoptosis by activating caspase-9 and caspase-3
      in apoptotic cascade. Bax-mediated apoptosis seems to be dependent on caspase-8
      activation because the inhibition of caspase-8 prevented Bid processing and Bax
      translocation. In conclusion, our dual gene virotherapy completely eliminated
      colorectal tumor xenografts via enhanced apoptosis, and this novel strategy
      points toward a new direction of cancer treatment.

PMID- 16618755
TI  - Discovery and evaluation of dual CDK1 and CDK2 inhibitors.
AB  - In eukaryotic cells, cyclin-dependent kinase (CDK) complexes regulate the
      temporal progression of cells through the cell cycle. Deregulation in the cell
      cycle is an essential component in the evolution of cancer. Here, we validate
      CDK1 and CDK2 as potential therapeutic targets using novel selective small
      molecule inhibitors of cyclin B1/CDK1 and cyclin E2/CDK2 enzyme complexes (CDKi).
      Flow cytometry-based methods were developed to assess intracellular
      retinoblastoma (Rb) phosphorylation to show inhibition of the CDK pathway. Tumor
      cells treated with CDK inhibitors showed an overall decrease in cell
      proliferation, accumulation of cells in G1 and G2, and apoptosis in a cell line
      specific manner. Although CDK inhibitors activate p53, the inhibitors were
      equipotent in arresting the cell cycle in isogenic breast and colon tumor cells
      lacking p53, suggesting the response is independent of p53. In vivo, the CDK
      inhibitors prevented the growth of colon and prostate tumors, blocked
      proliferation of tumor cells, and inhibited Rb phosphorylation. The discovery and
      evaluation of novel potent and selective CDK1 and CDK2 inhibitors will help
      delineate the role that CDK complexes play in regulating tumorigenesis.

PMID- 16618756
TI  - Crosstalk between extrinsic and intrinsic cell death pathways in pancreatic
      cancer: synergistic action of estrogen metabolite and ligands of death receptor
      family.
AB  - 2-Methoxyestradiol is a physiologic metabolite of 17beta-estradiol. This orally
      active compound can inhibit tumor growth or metastasis in tumor models without
      inducing any clinical sign of toxicity. Our previous studies indicated that 2
      methoxyestradiol-mediated apoptosis involves the disappearance of intact 21-kDa
      Bid protein, cytochrome c release, and predominant procaspase-3 cleavage. Here,
      using MIA PaCa-2 cells as a model, we investigated whether this estrogen
      metabolite induces apoptosis by converging two major pathways: the death receptor
      mediated extrinsic and the mitochondrial intrinsic pathway. Exogenous expression
      of dominant-negative caspase-8 or dominant-negative FADD reverts the effect of 2
      methoxyestradiol-mediated cell death. In parallel with this observation, Z-IETD
      FMK, a cell permeable irreversible inhibitor of caspase-8, can render significant
      protection against 2-methoxyestradiol-induced apoptosis. RNase protection assay
      and cell surface receptor analysis by flow cytometry show the up-regulation of
      members of death receptor family in 2-methoxyestradiol-exposed pancreatic cancer
      cells. Our mechanistic studies also implicate that oxidative stress precedes 2
      methoxyestradiol-mediated c-Jun NH2-terminal kinase activation, leading to
      elevated Fas level. Because 2-methoxyestradiol is able to trigger death receptor
      signaling, we were interested in examining the effects of 2-methoxyestradiol and
      Fas ligand (FasL)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      together on pancreatic cancer cell death. Interestingly, the endogenous
      angiogenesis inhibitor 2-methoxyestradiol augments FasL/TRAIL-induced apoptosis
      in these cells. Moreover, the combination of 2-methoxyestradiol and TRAIL reduces
      the tumor burden in vivo in MIA PaCa-2 tumor xenograft model by caspase-3
      activation.

PMID- 16618757
TI  - Adeno-associated virus-mediated delivery of a mutant endostatin in combination
      with carboplatin treatment inhibits orthotopic growth of ovarian cancer and
      improves long-term survival.
AB  - A human ovarian cancer cell line, which migrates to mouse ovaries and establishes
      peritoneal carcinomatosis, was used to evaluate the cooperative effect of an
      antiangiogenic gene therapy combined with chemotherapy. The ovarian carcinoma
      cell line MA148 was genetically modified by "Sleeping Beauty" transposon-mediated
      delivery of DsRed2 fluorescent protein. Stable, high-level expression of DsRed
      protein enabled in vivo imaging of peritoneal dissemination of ovarian cancer.
      Both external and internal imaging, along with histopathology, showed migration
      of i.p. injected human ovarian cancer cell line to mouse ovaries. Using this
      model, we evaluated the effect of adeno-associated virus (AAV)-mediated
      expression of a mutant endostatin either alone or in combination with carboplatin
      treatment. A single i.m. injection of recombinant AAV (rAAV)-mutant human
      endostatin with P125A substitution (P125A-endostatin) showed sustained expression
      of mutant endostatin. Antiangiogenic gene therapy inhibited orthotopic growth of
      ovarian cancer and resulted in 33% long-term tumor-free survival. A single cycle
      of carboplatin treatment combined with mutant endostatin gene therapy resulted in
      60% of the animals remaining tumor free for >200 days, which was significantly
      better than rAAV-LacZ and/or carboplatin. Combination treatment delayed tumor
      appearance in 40% of the animals, wherein the residual tumors were smaller in
      size with limited or no peritoneal metastasis. These studies suggest that AAV
      mediated gene therapy of P125A-endostatin in combination with carboplatin is a
      useful method to inhibit peritoneal dissemination of ovarian carcinoma.

PMID- 16618758
TI  - Phospholipase C-delta1 is a critical target for tumor necrosis factor receptor
      mediated protection against adriamycin-induced cardiac injury.
AB  - The clinical application of adriamycin, an exceptionally good chemotherapeutic
      agent, is limited by its dose-related cardiomyopathy. Our recent study showed
      that tumor necrosis factor-alpha (TNF-alpha) receptors mediated cytoprotective
      signaling against adriamycin-induced mitochondrial injury and cardiomyocyte
      apoptosis. In the present study, we investigated the potential targets of TNF
      receptor-mediated cytoprotective signaling by global genome microarray analysis
      using wild-type and TNF receptor-deficient mice. Microarray analysis revealed
      that adriamycin treatment induced the down-regulation of several mitochondrial
      functions and energy production-related genes in double TNF receptor-deficient
      mice, notably, phospholipase C-delta1, a protein involved in fatty acid
      metabolism and calcium regulation. The role of phospholipase C-delta1 in TNF
      receptor-mediated cardioprotection against adriamycin-induced injury was
      evaluated by measuring changes in cardiac function using high-frequency
      ultrasound biomicroscopy. Selective inhibition of phospholipase C activity in
      wild-type mice by its inhibitor, U73122, exacerbated adriamycin-induced cardiac
      dysfunction. Inhibition of phospholipase C-delta1 resulted in the significant
      decrease of left ventricular ejection fraction and fractional shortening, and the
      decreased levels were similar to those observed in adriamycin-treated double TNF
      receptor-deficient mice. The data derived from the global genome analysis
      identified phospholipase C-delta1 as an important target for TNF receptors and
      revealed the critical role of TNF receptor signaling in the protection against
      adriamycin-induced cardiotoxicity.

PMID- 16618759
TI  - Tumor imaging using a picomolar affinity HER2 binding affibody molecule.
AB  - The detection of cell-bound proteins that are produced due to aberrant gene
      expression in malignant tumors can provide important diagnostic information
      influencing patient management. The use of small radiolabeled targeting proteins
      would enable high-contrast radionuclide imaging of cancers expressing such
      antigens if adequate binding affinity and specificity could be provided. Here, we
      describe a HER2-specific 6 kDa Affibody molecule (hereinafter denoted Affibody
      molecule) with 22 pmol/L affinity that can be used for the visualization of HER2
      expression in tumors in vivo using gamma camera. A library for affinity
      maturation was constructed by re-randomization of relevant positions identified
      after the alignment of first-generation variants of nanomolar affinity (50
      nmol/L). One selected Affibody molecule, Z(HER2:342) showed a >2,200-fold
      increase in affinity achieved through a single-library affinity maturation step.
      When radioiodinated, the affinity-matured Affibody molecule showed clear, high
      contrast visualization of HER2-expressing xenografts in mice as early as 6 hours
      post-injection. The tumor uptake at 4 hours post-injection was improved 4-fold
      (due to increased affinity) with 9% of the injected dose per gram of tissue in
      the tumor. Affibody molecules represent a new class of affinity molecules that
      can provide small sized, high affinity cancer-specific ligands, which may be well
      suited for tumor imaging.

PMID- 16618760
TI  - Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7
      breast cancer xenografts.
AB  - Overexpression of colony-stimulating factor-1 (CSF-1) and its receptor in breast
      cancer is correlated with poor prognosis. Based on the hypothesis that blockade
      of CSF-1 would be beneficial in breast cancer treatment, we developed a
      murinized, polyethylene glycol-linked antigen-binding fragment (Fab) against
      mouse (host) CSF-1 (anti-CSF-1 Fab). Mice bearing human, chemoresistant MCF-7
      breast cancer xenografts were treated with combination chemotherapy (CMF:
      cyclophosphamide, methotrexate, 5-fluorouracil; cycled twice i.p.), anti-CSF-1
      Fab (i.p., cycled every 3 days for 14 days), combined CMF and anti-CSF-1 Fab, or
      with Ringer's solution as a control. Anti-CSF-1 Fab alone suppressed tissue CSF-1
      and retarded tumor growth by 40%. Importantly, in combination with CMF, anti-CSF
      1 Fab reversed chemoresistance of MCF-7 xenografts, suppressing tumor development
      by 56%, down-regulating expression of the chemoresistance genes breast cancer
      related protein, multidrug resistance gene 1, and glucosylceramide synthase, and
      prolonging survival significantly. Combined treatment also reduced angiogenesis
      and macrophage recruitment and down-regulated tumor matrix metalloproteinase-2
      (MMP-2) and MMP-12 expression. These studies support the paradigm of CSF-1
      blockade in the treatment of solid tumors and show that anti-CSF-1 antibodies are
      potential therapeutic agents for the treatment of mammary cancer.

PMID- 16618761
TI  - Inactivation of human MAD2B in nasopharyngeal carcinoma cells leads to
      chemosensitization to DNA-damaging agents.
AB  - Rev7p has been suggested to play an important role in regulating DNA damage
      response in yeast, and recently, the human homologue (i.e., MAD2B) has been
      identified, which shares significant homology to the mitotic checkpoint protein
      MAD2. In this study, we investigated whether MAD2B played a key role in cellular
      sensitivity to DNA-damaging anticancer drugs by suppressing its expression using
      RNA interference in nasopharyngeal carcinoma cells. Using colony formation assay,
      we found that suppression of MAD2B conferred hypersensitivity to a range of DNA
      damaging agents, especially DNA cross-linkers, such as cisplatin, and gamma
      irradiation. This effect was associated with reduced frequencies of spontaneous
      and drug-induced mutations, elevated phosphorylation of histone H2AX, and
      markedly increased chromosomal aberrations in response to DNA damage. In
      addition, there was also a significant decrease in cisplatin-induced sister
      chromatid exchange rate, a marker for homologous recombination-mediated post
      replication repair in MAD2B-depleted cells. These results indicate that MAD2B may
      be a key factor in regulating cellular response to DNA damage in cancer cells.
      Our findings reveal a novel strategy for cancer therapy, in which cancer cells
      are sensitized to DNA-damaging anticancer drugs through inactivation of the MAD2B
      gene.

PMID- 16618762
TI  - Antitumor activity of a small-molecule inhibitor of human silent information
      regulator 2 enzymes.
AB  - SIRT1 and other NAD-dependent deacetylases have been implicated in control of
      cellular responses to stress and in tumorigenesis through deacetylation of
      important regulatory proteins, including p53 and the BCL6 oncoprotein. Hereby, we
      describe the identification of a compound we named cambinol that inhibits NAD
      dependent deacetylase activity of human SIRT1 and SIRT2. Consistent with the role
      of SIRT1 in promoting cell survival during stress, inhibition of SIRT1 activity
      with cambinol during genotoxic stress leads to hyperacetylation of key stress
      response proteins and promotes cell cycle arrest. Treatment of BCL6-expressing
      Burkitt lymphoma cells with cambinol as a single agent induced apoptosis, which
      was accompanied by hyperacetylation of BCL6 and p53. Because acetylation
      inactivates BCL6 and has the opposite effect on the function of p53 and other
      checkpoint pathways, the antitumor activity of cambinol in Burkitt lymphoma cells
      may be accomplished through a combined effect of BCL6 inactivation and checkpoint
      activation. Cambinol was well tolerated in mice and inhibited growth of Burkitt
      lymphoma xenografts. Inhibitors of NAD-dependent deacetylases may constitute
      novel anticancer agents.

PMID- 16618763
TI  - Inhibition of cyclooxygenase-2 disrupts tumor vascular mural cell recruitment and
      survival signaling.
AB  - Much evidence supports an important role for the inducible enzyme cyclooxygenase
      2 (COX-2) in tumor angiogenesis. Previous studies have focused on the role of COX
      2 in stimulating endothelial proliferation, with blockade of this enzyme
      impairing endothelial homeostasis. However, recent data suggest that COX-2 also
      regulates molecules implicated in endothelial trafficking with pericytes/vascular
      mural cells (VMC), an interaction crucial to vessel stability. We investigated
      the role of COX-2 in vascular assembly by testing the effect of the specific COX
      2 inhibitor SC-236 in an orthotopic xenograft model of human Wilms' tumor. Tumor
      growth was significantly suppressed by SC-236 (78% at day 28, 55% at day 35).
      Perfusion studies and immunostaining showed a marked decrease in vasculature,
      particularly in small vessels. Specifically, SC-236 inhibited participation of
      VMC in xenograft vessels. SC-236-treated tumors developed segmentally dilated,
      architecturally erratic tumor vessels with decreased nascent pericytes and scant
      mature VMC. Although vascular endothelial growth factor expression was unchanged,
      expression of the chemokine receptor CXCR4 was decreased in tumor vessels,
      consistent with defective homing of vascular progenitor cells. Vascular
      expression of phosphorylated platelet-derived growth factor receptor-beta was
      also diminished, indicating impaired VMC-endothelial trafficking. Consistent with
      the key role of this interaction in vessel homeostasis, vascular cells in SC-236
      treated tumors displayed markedly diminished phosphorylated Akt, indicating
      disrupted survival signaling. These results show that SC-236 causes defective
      vascular assembly by attenuating incorporation of VMC into tumor vessels,
      impairing endothelial survival, and raise the possibility that blockade of COX-2
      may provide therapeutic synergies with antiangiogenic molecules that more
      selectively target endothelial cells.

PMID- 16618764
TI  - 1-Methoxy-canthin-6-one induces c-Jun NH2-terminal kinase-dependent apoptosis and
      synergizes with tumor necrosis factor-related apoptosis-inducing ligand activity
      in human neoplastic cells of hematopoietic or endodermal origin.
AB  - We investigated the effects of 1-methoxy-canthin-6-one, isolated from the
      medicinal plant Ailanthus altissima Swingle, on apoptosis in human leukemia
      (Jurkat), thyroid carcinoma (ARO and NPA), and hepatocellular carcinoma (HuH7)
      cell lines. Cultures incubated with the compound showed >50% of sub-G1
      (hypodiploid) elements in flow cytometry analysis; the apoptosis-inducing
      activity was evident at <10 micromol/L and half-maximal at about 40 micromol/L 1
      methoxy-canthin-6-one. The appearance of hypodiploid elements was preceded by
      mitochondrial membrane depolarization, mitochondrial release of cytochrome c, and
      Smac/DIABLO and procaspase-3 cleavage. We subsequently investigated the effect of
      1-methoxy-canthin-6-one in combination with human recombinant tumor necrosis
      factor-related apoptosis-inducing ligand (TRAIL) in the four cell lines.
      Suboptimal concentrations (10 micromol/L 1-methoxy-canthin-6-one and 0.25 ng/mL
      TRAIL, respectively) of the two agents, unable to elicit apoptosis when used
      alone, induced mitochondrial depolarization, activation of caspase-3, and 45% to
      85% of sub-G1 elements when added together to the cells. The synergism seemed to
      rely partly on the enhanced expression of TRAIL receptor 1 (TRAIL-R1; DR4),
      analyzed by immunofluorescence, by 1-methoxy-canthin-6-one. Cell incubation with
      1-methoxy-canthin-6-one resulted in activating c-Jun NH2-terminal kinase (JNK),
      as revealed by Western blotting; induction of apoptosis and TRAIL-R1 up
      regulation by 1-methoxy-canthin-6-one were >80% prevented by the addition of the
      JNK inhibitor (JNKI) SP600125JNKI, indicating that both effects were almost
      completely mediated by JNK activity. On the other hand, synergism with TRAIL was
      reduced by about 50%, suggesting that besides up-regulating TRAIL-R1, 1-methoxy
      canthin-6-one could influence other factor(s) that participated in TRAIL-induced
      apoptosis. These findings indicate that 1-methoxy-canthin-6-one can represent a
      candidate for in vivo studies of monotherapies or combined antineoplastic
      therapies.

PMID- 16618765
TI  - Ligand activation of peroxisome proliferator-activated receptor beta inhibits
      colon carcinogenesis.
AB  - There is considerable debate whether peroxisome proliferator-activated receptor
      beta/delta (PPARbeta/delta) ligands potentiate or suppress colon carcinogenesis.
      Whereas administration of a PPARbeta ligand causes increased small intestinal
      tumorigenesis in Apc(min/+) mice, PPARbeta-null (Pparb-/-) mice exhibit increased
      colon polyp multiplicity in colon cancer bioassays, suggesting that ligand
      activation of this receptor will inhibit colon carcinogenesis. This hypothesis
      was examined by treating wild-type (Pparb+/+) and Pparb-/- with azoxymethane,
      coupled with a highly specific PPARbeta ligand, GW0742. Ligand activation of
      PPARbeta in Pparb+/+ mice caused an increase in the expression of mRNA encoding
      adipocyte differentiation-related protein, fatty acid-binding protein, and
      cathepsin E. These findings are indicative of colonocyte differentiation, which
      was confirmed by immunohistochemical analysis. No PPARbeta-dependent differences
      in replicative DNA synthesis or expression of phosphatase and tensin homologue,
      phosphoinositide-dependent kinase, integrin-linked kinase, or phospho-Akt were
      detected in ligand-treated mouse colonic epithelial cells although increased
      apoptosis was found in GW0742-treated Pparb+/+ mice. Consistent with increased
      colonocyte differentiation and apoptosis, inhibition of colon polyp multiplicity
      was also found in ligand-treated Pparb+/+ mice, and all of these effects were not
      found in Pparb-/- mice. In contrast to previous reports suggesting that
      activation of PPARbeta potentiates intestinal tumorigenesis, here we show that
      ligand activation of PPARbeta attenuates chemically induced colon carcinogenesis
      and that PPARbeta-dependent induction of cathepsin E could explain the reported
      disparity in the literature about the effect of ligand activation of PPARbeta in
      the intestine.

PMID- 16618767
TI  - Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications
      for myricetin and quercetin anticancer activity.
AB  - The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin
      (Trx), and NADPH, exerts a wide range of activities in cellular redox control,
      antioxidant function, cell viability, and proliferation. Recently, the
      selenocysteine (Sec)-containing mammalian TrxR has emerged as a new target for
      anticancer drug development because TrxR and Trx are overexpressed in many
      aggressive tumors and the tumor cells seem to be more dependent on Trx system
      than normal cells. Here we have investigated the inhibition of mammalian TrxR by
      flavonoids which have been presumed to be cancer chemoprevention agents because
      of their antioxidant activities. Myricetin and quercetin were found to have
      strong inhibitory effects on mammalian TrxRs with IC50 values of 0.62 and 0.97
      micromol/L, respectively. The inhibition was shown to be concentration, NADPH,
      and time dependent and involved an attack on the reduced COOH-terminal -Cys-Sec
      Gly active site of TrxR. Oxygen-derived superoxide anions enhanced the inhibitory
      effect whereas anaerobic conditions attenuated inhibition. Spectral analysis
      suggested that the flavonols might perform their inhibitory effects via
      semiquinone radicals. Additionally, the flavonols had the potential to inhibit
      the growth of A549 cells with the same potency as inhibition of TrxR. TrxR
      activity in the cell lysates was reduced on treatment with myricetin >50
      micromol/L, which coincided with the oxidization of Trx. The cell cycle was
      arrested in S phase by quercetin and an accumulation of cells in sub-G1 was
      observed in response to myricetin. Thus, the anticancer activity of quercetin and
      myricetin may be due to inhibition of TrxR, consequently inducing cell death.

PMID- 16618766
TI  - The requirement for and changing composition of the activating protein-1
      transcription factor during differentiation of human leukemia HL60 cells induced
      by 1,25-dihydroxyvitamin D3.
AB  - The activating protein-1 (AP-1) transcription factor complex is a heterogeneous
      entity, composed in mammalian cells of dimers chosen from a group of at least
      eight proteins belonging to three families: jun, fos, and activating
      transcription factor (ATF). The AP-1 complexes participate in diverse biological
      processes that include cell proliferation, survival, and differentiation. These
      seemingly contrasting functions have been attributed to the intensity and
      duration of the signals provided by AP-1, but the biological consequences of
      changing composition of the AP-1 complex have not been fully explored. Here, we
      show that functional AP-1 is required for 1,25-dihydroxyvitamin D3 (1,25D)
      induced monocytic differentiation, and that the composition of the AP-1 protein
      complex that binds TRE, its cognate DNA element, changes as cells differentiate.
      In HL60 cells in an early stage of differentiation, the principal AP-1 components
      detected by gel shift analysis include c-jun, ATF-2, fos-B, fra-1, and fra-2. In
      cells with a more established monocytic phenotype, the demonstrable AP-1
      components are c-jun, ATF-2, jun-B, and fos-B. Following the addition of 1 nmol/L
      of 1,25D, the cellular content of each of these four proteins markedly increased
      in a sustained manner, whereas the increases in c-fos, fra-1, fra-2, and jun-D
      were minimal, if any. Small increases in mRNA levels encoding all AP-1 component
      proteins, except c-fos, were also noted. These findings provide a basis for the
      previously found participation of the c-Jun N-terminal kinase pathway in 1,25D
      induced differentiation of myeloid leukemia cells, and direct attention to jun-B
      and fos-B as new cellular therapeutic targets, that may promote replicative
      quiescence associated with differentiation of malignant cells.

PMID- 16618768
TI  - Insulin-like growth factor I secreted from prostate stromal cells mediates tumor
      stromal cell interactions of prostate cancer.
AB  - Prostate cancer shows high expression of type I insulin-like growth factor (IGF
      I) receptor (IGF-IR) and prostate stromal cells (PrSC) produce IGF-I. Although
      high plasma level of IGF-I is a risk factor of prostate cancer, the significance
      of the prostate stromal IGF-I in the regulation of prostate cancer remains
      elusive. Here we show that the stromal IGF-I certainly regulates the development
      of prostate cancer. Coinoculation of PrSC increased the growth of human prostate
      cancer LNCaP and DU-145 tumors in severe combined immunodeficient mice. The
      conditioned medium of PrSC, as well as IGF-I, induced phosphorylation of IGF-IR
      and increased the growth of LNCaP and DU-145 cells. PrSC, but not LNCaP and DU
      145 cells, secreted significant amounts of IGF-I. Coculture with PrSC increased
      the growth of DU-145 cells in vitro but the pretreatment of PrSC with small
      interfering RNA of IGF-I did not enhance it. Furthermore, various chemical
      inhibitors consisting of 79 compounds with approximately 60 different targets led
      to the finding that only IGF-IR inhibitor suppressed the PrSC-induced growth
      enhancement of DU-145 cells. Thus, these results show that the prostate stromal
      IGF-I mediates tumor-stromal cell interactions of prostate cancer to accelerate
      tumor growth, supporting the idea that the IGF-I signaling is a valuable target
      for the treatment of prostate cancer.

PMID- 16618769
TI  - Antibody-maytansinoid conjugates are activated in targeted cancer cells by
      lysosomal degradation and linker-dependent intracellular processing.
AB  - Antibody-drug conjugates are targeted anticancer agents consisting of a cytotoxic
      drug covalently linked to a monoclonal antibody for tumor antigen-specific
      activity. Once bound to the target cell-surface antigen, the conjugate must be
      processed to release an active form of the drug, which can reach its
      intracellular target. Here, we used both biological and biochemical methods to
      better define this process for antibody-maytansinoid conjugates. In particular,
      we examined the metabolic fate in cells of huC242-maytansinoid conjugates
      containing either a disulfide linker (huC242-SPDB-DM4) or a thioether linker
      (huC242-SMCC-DM1). Using cell cycle analysis combined with lysosomal inhibitors,
      we showed that lysosomal processing is required for the activity of antibody
      maytansinoid conjugates, irrespective of the linker. We also identified and
      characterized the released maytansinoid molecules from these conjugates, and
      measured their rate of release compared with the kinetics of cell cycle arrest.
      Both conjugates are efficiently degraded in lysosomes to yield metabolites
      consisting of the intact maytansinoid drug and linker attached to lysine. The
      lysine adduct is the sole metabolite from the thioether-linked conjugate.
      However, the lysine metabolite generated from the disulfide-linked conjugate is
      reduced and S-methylated to yield the lipophilic and potently cytotoxic
      metabolite, S-methyl-DM4. These findings provide insight into the mechanism of
      action of antibody-maytansinoid conjugates in general, and more specifically,
      identify a biochemical mechanism that may account for the significantly enhanced
      antitumor efficacy observed with disulfide-linked conjugates.

PMID- 16618770
TI  - Characterization of a novel human tumor antigen interleukin-13 receptor alpha2
      chain.
AB  - The interleukin (IL)-13 receptor alpha2 (IL-13Ralpha2) chain is a primary binding
      and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13.
      Although extremely high levels of IL-13Ralpha2 chain are expressed on a variety
      of human tumor cells and specimens, its precise role in tumor immunology has not
      been defined. To investigate the role of IL-13Ralpha2 in tumor immunity, we used
      D5 melanoma cells stably transfected with the human IL-13Ralpha2 gene (D5alpha2)
      to assess the effect of an IL-13Ralpha2 DNA vaccine in immunocompetent animals.
      Prophylactic immunization of mice with the IL-13Ralpha2 DNA vaccine resulted in
      protection against D5alpha2 tumor development. In vivo depletion experiments in
      C57BL/6 and RAG-2 knockout mice indicated that both T and B cells, but not
      natural killer cells, were required for the tumor protection. In addition,
      antibody induced by the IL-13Ralpha2 DNA vaccine showed a modest but significant
      inhibitory effect on D5alpha2 cells in vitro, suggesting that the antibody is
      biologically functional. The IL-13Ralpha2 DNA vaccine also exhibited antitumor
      activity against established D5alpha2 tumors in mice. Histologic analysis of
      regressing tumors identified infiltration of CD4+ and CD8+ T cells and the
      expression of CXCL9 chemokine in tumors. Taken together, our results identify the
      human IL-13Ralpha2 chain as a novel tumor rejection antigen.

PMID- 16618771
TI  - A new melanoma antigen fatty acid-binding protein 7, involved in proliferation
      and invasion, is a potential target for immunotherapy and molecular target
      therapy.
AB  - The identification of molecules that are preferentially expressed in melanoma
      cells and involved in their malignant phenotypes is important for understanding
      melanoma biology and the development of new diagnostic and therapeutic methods.
      By comparing the expression profile of a melanoma cell line with those of various
      normal tissues using GeneChip and by confirming the actual expression of the
      selected genes by reverse transcription-PCR and Northern and Western blot
      analyses, fatty acid-binding protein 7 (FABP7), which is frequently expressed in
      melanomas, was identified. Immunohistochemical examination revealed that FABP7
      was expressed in 11 of 15 melanoma tissues. By down-regulating the FABP7
      expression with FABP7-specific small interfering RNAs, in vitro cell
      proliferation and Matrigel invasion were suppressed in two of six melanoma cell
      lines. Overexpression of FABP7 in a FABP7-negative embryonic kidney cell line
      293T by transfecting with the FABP7 cDNA resulted in enhanced cell proliferation
      and Matrigel invasion, indicating that FABP7 plays a role in the malignant
      phenotype of some melanoma cell lines. IgG antibodies specific for the phage or
      bacterial recombinant FABP7 protein were detected in 14 of 25 (56%) or in 8 of 31
      (26%) sera from melanoma patients, respectively, but not in sera from healthy
      individuals, indicating that FABP7 is an immunogenic antigen in melanoma
      patients. These results showed that FABP7 is frequently expressed in melanoma,
      may be involved in cell proliferation and invasion, and may be a potential target
      for development of diagnostic and therapeutic methods.

PMID- 16618772
TI  - Soluble human LAG-3 molecule amplifies the in vitro generation of type 1 tumor
      specific immunity.
AB  - The adjuvant activities of the human lymphocyte activation gene-3 (LAG-3)
      molecule have been evaluated in a human setting by investigating the ability of a
      soluble recombinant human LAG-3 protein (hLAG-3Ig) to enhance the in vitro
      induction of viral- and tumor-specific CTLs. We found that soluble human LAG-3
      significantly sustained the generation and expansion of influenza matrix protein
      Melan-A/MART-1 and survivin-specific CD8+ T lymphocytes in peripheral blood
      mononuclear cells (PBMC) of both cancer patients and healthy donors, showing its
      ability to boost CD8+ T-cell memory response or to prime naive T cells in vitro.
      The peptide-specific T cells generated in the presence of hLAG-3Ig were endowed
      with cytotoxic activity and enhanced release of type 1 cytotoxic T (Tc1)
      cytokines and were able to recognize tumor cells expressing their nominal
      antigen. Phenotype and cytokine/chemokines produced by antigen-presenting cells
      (APC) of PBMCs exposed in vitro for 2 days to peptide and hLAG-3Ig indicate that
      the LAG-3-mediated adjuvant effect may depend on a direct activation of
      circulating APCs. Our data revealed the activity of hLAG-3Ig in inducing tumor
      associated, antigen-specific CD8+ T-cell responses in a human setting and
      strongly support the conclusion that this recombinant protein is a potential
      candidate adjuvant for cancer vaccines.

PMID- 16618773
TI  - Stat1 deficiency in the host enhances interleukin-12-mediated tumor regression.
AB  - Signal transducer and activator of transcription 1 (Stat1) is considered a key
      transcription factor that inhibits tumorigenesis, and Stat1 activation in the
      host is required for interleukin-12 (IL-12)-mediated generation of CTL activity.
      Using syngeneic Stat1-/- C3H mice bearing SCCVII tumors in this study, we
      discovered opposite results. Stat1 deficiency in the host significantly enhances
      IL-12-mediated tumor regression, resulting in tumor eradication from 60% of
      SCCVII tumor-bearing mice and significant inhibition of tumor growth when
      compared with control treatment (P < 0.01). This effect is independent of both
      Stat1-activating cytokine IFN-gamma and Stat1-downstream effector molecule FasL
      because neither neutralization of IFN-gamma nor knocking out of FasL enhances or
      inhibits IL-12-mediated tumor regression. IL-12 induces a high intensity of tumor
      specific CTL activity in Stat1-deficient mice (P < 0.01), increases the CD8 T
      cell density in tumor bearing Stat1-/- mice, and induces a T-cell-dependent tumor
      regression. The increased CTL activity and the high-intensity infiltration of T
      cells into the tumors in IL-12-treated Stat1-/- mice are likely due to the longer
      survival than the same cells from wild-type mice. Together, the data show that
      inhibition of Stat1 expression in the host enhances tumor-local IL-12 gene
      therapy for regressing tumors. This conclusion provides a new concept for
      designing an effective treatment strategy.

PMID- 16618774
TI  - Characterization of the mouse IFN-lambda ligand-receptor system: IFN-lambdas
      exhibit antitumor activity against B16 melanoma.
AB  - Recently discovered type III IFNs (IFN-lambda) exert their antiviral and
      immunomodulatory activities through a unique receptor complex composed of IFN
      lambdaR1 and interleukin-10 receptor 2. To further study type III IFNs, we cloned
      and characterized mouse IFN-lambda ligand-receptor system. We showed that,
      similar to their human orthologues, mIFN-lambda2 and mIFN-lambda3 signal through
      the IFN-lambda receptor complex, activate IFN stimulated gene factor 3, and are
      capable of inducing antiviral protection and MHC class I antigen expression in
      several cell types including B16 melanoma cells. We then used the murine B16
      melanoma model to investigate the potential antitumor activities of IFN-lambdas.
      We developed B16 cells constitutively expressing murine IFN-lambda2 (B16.IFN
      lambda2 cells) and evaluated their tumorigenicity in syngeneic C57BL/6 mice.
      Although constitutive expression of mIFN-lambda2 in melanoma cells did not affect
      their proliferation in vitro, the growth of B16.IFN-lambda2 cells, when injected
      s.c. into mice, was either retarded or completely prevented. We found that
      rejection of the modified tumor cells correlated with their level of IFN-lambda2
      expression. We then developed IFN-lambda-resistant B16.IFN-lambda2 cells (B16.IFN
      lambda2Res cells) and showed that their tumorigenicity was also highly impaired
      or completely abolished similar to B16.IFN-lambda2 cells, suggesting that IFN
      lambdas engage host mechanisms to inhibit melanoma growth. These in vivo
      experiments show the antitumor activities of IFN-lambdas and suggest their strong
      therapeutic potential.

PMID- 16618775
TI  - Adoptive transfer of type 1 CTL mediates effective anti-central nervous system
      tumor response: critical roles of IFN-inducible protein-10.
AB  - The development of effective immunotherapeutic strategies for central nervous
      system (CNS) tumors requires a firm understanding of factors regulating the
      trafficking of tumor antigen-specific CTLs into CNS tumor lesions. Using C57BL/6
      mice bearing intracranial (i.c.) ovalbumin-transfected melanoma (M05), we
      evaluated the efficacy and tumor homing of i.v. transferred type 1 or 2 CTLs (Tc1
      or Tc2, respectively) prepared from ovalbumin-specific T-cell receptor-transgenic
      OT-1 mice. We also tested our hypothesis that intratumoral (i.t.) delivery of
      dendritic cells that had been transduced with IFN-alpha cDNA (DC-IFN-alpha) would
      enhance the tumor-homing and antitumor effectiveness of adoptively transferred
      Tc1 via induction of an IFN-gamma-inducible protein 10 (IP-10). In vitro, DC-IFN
      alpha induced IP-10 production by M05 and enhanced the cytolytic activity of Tc1.
      In vivo, i.v. transferred Tc1 trafficked efficiently into i.c. M05 and mediated
      antitumor responses more effectively than Tc2, and their effect was IP-10
      dependent. I.t. injections of DC-IFN-alpha remarkably enhanced the tumor homing,
      therapeutic efficacy, and in situ IFN-gamma production of i.v. delivered Tc1,
      resulting in the long-term survival and persistence of systemic ovalbumin
      specific immunity. These data suggest that Tc1-based adoptive transfer therapy
      may represent an effective modality for CNS tumors, particularly when combined
      with strategies that promote a type 1 polarized tumor microenvironment.

PMID- 16618776
TI  - Tumor-induced expansion of regulatory T cells by conversion of CD4+CD25-
      lymphocytes is thymus and proliferation independent.
AB  - The CD25- and CD25+ CD4 T-lymphocyte compartments are tightly regulated. We show
      here that tumors break such balance, increasing the number of CD4+CD25+ T cells
      in draining lymph node and spleen but not contralateral node of tumor-bearing
      mice. Tumor injection in thymectomized and CD25-depleted mice shows that
      CD4+CD25+ T-cell expansion occurs even in the absence of the thymus and
      independently from proliferation of preexisting CD25+ T cells. These newly
      generated cells are bona fide regulatory T cells (T reg) in terms of Foxp3
      expression and suppression of CD3-stimulated or allogeneic effector cell
      proliferation. Transfer of congenic Thy1.1 CD4+CD25- T cells, from mice treated
      or not with vinblastine, into tumor-bearing or tumor-free mice and analysis of
      recovered donor lymphocytes indicate that conversion is the main mechanism for
      acquiring the expression of CD25 and Foxp3 through a process that does not
      require proliferation. Although conversion of CD4+CD25- T cells for generation of
      T regs has been described as a natural process that maintains peripheral T-reg
      population, this process is used by the tumor for immune escape. The prompt
      recovery of T regs from monoclonal antibody-mediated CD25 depletion in tumor
      bearing mice suggests attempts able to inactivate rather than deplete them when
      treating existing tumors.

PMID- 16618777
TI  - Phase I trial of a novel intradermal idiotype vaccine in patients with advanced B
      cell lymphoma: specific immune responses despite profound immunosuppression.
AB  - The immunoglobulin receptor of B-cell lymphomas constitutes a specific tumor
      antigen (idiotype) and a target for active immunotherapy. Encouraging results
      have been reported in phase II trials after s.c. vaccination of follicular
      lymphoma patients during clinical remission with idiotype produced from
      eukaryotic cell lines and coupled to an immunogenic carrier macromolecule. We
      have developed a good manufacturing protocol for rapid expression of idiotype
      vaccines as recombinant Fab fragments in Escherichia coli. The objectives of this
      trial were to show safety and feasibility of intradermal immunization with this
      vaccine and to investigate whether immune responses were induced by this
      immunization route. Patients (n = 18) with advanced B-cell malignancies received
      repetitive intradermal vaccinations with 0.5 to 1.65 mg recombinant idiotype Fab
      fragment mixed with lipid-based adjuvant in combination with 150 mug granulocyte
      macrophage colony-stimulating factor s.c. at the same location. The patients'
      immune status was assessed by flow cytometry of peripheral blood lymphocytes and
      concomitant hepatitis B vaccination. Cellular and humoral immune responses to the
      vaccine were assessed by enzyme-linked immunospot and ELISA. Side effects of a
      total of 65 vaccinations were mild and did not affect the immunization schedule.
      No patient developed hepatitis B surface antibodies (anti-HBs) after two
      hepatitis B immunizations. Of 17 evaluable patients, five developed specific anti
      vaccine antibodies, and eight developed anti-Fab T-cell responses. T-cell
      reactivity was independent of the cellular immune status and was idiotype
      specific as shown by statistical regression analysis (P = 0.0024) and epitope
      mapping studies. Intradermal administration of uncoupled recombinant idiotype
      with appropriate adjuvants may overcome profound clinical immunosuppression and
      induce specific immune responses.

PMID- 16618778
TI  - Nitric oxide-donating aspirin prevents pancreatic cancer in a hamster tumor
      model.
AB  - To evaluate the chemopreventive effect of nitric oxide-donating aspirin (NO-ASA),
      an ASA bearing a NO-releasing moiety, against pancreatic cancer, we studied six
      groups of female Syrian golden hamsters: groups 1 to 3 (n = 12 each) were given
      saline and groups 4 to 6 (n = 17) the carcinogen N-nitrosobis(2-oxopropyl)amine
      (BOP) s.c. in five weekly injections (the first, 70 mg/kg, and the remaining, 20
      mg/kg each). Control and BOP-treated hamsters were fed a NO-ASA 3,000 ppm or
      conventional ASA 3,000 ppm or control diet for 19 weeks. Groups 1 to 3 had no
      tumors. Compared with the BOP/vehicle group, NO-ASA reduced the incidence (88.9%,
      P < 0.003) and multiplicity (94%, P < 0.05) of pancreatic cancer; ASA had no
      statistically significant effect. NO-ASA arrested the transition from PanIN2 to
      PanIN3 and carcinoma. The proliferation (proliferating cell nuclear antigen) /
      apoptosis (terminal deoxyribonucleotide transferase-mediated nick-end labeling)
      ratio of ductal cells increased with the histologic severity of the ductal
      lesion; NO-ASA suppressed it significantly during all stages except PanIN1A.
      p21(WAF1/CIP1), undetectable in normal cells, was progressively induced in
      neoplastic cells and suppressed by NO-ASA up to PanIN3. Nuclear factor-kappaB
      activation, absent in normal tissue, increased progressively (17-fold in cancer);
      NO-ASA suppressed it throughout and significantly in PanIN1B and PanIN2.
      Cyclooxygenase-2 expression, absent during early stages, was induced 6-fold in
      carcinoma and suppressed by NO-ASA in PanIN3 and carcinoma. Conventional ASA had
      no effect on these molecular markers. Thus, NO-ASA profoundly prevented
      pancreatic cancer and modulated multiple molecular targets in this model system;
      conventional ASA had no such effects. NO-ASA merits further evaluation as a
      chemopreventive agent against pancreatic cancer.

PMID- 16618779
TI  - Duration but not intensity of alcohol and tobacco exposure predicts p16INK4A
      homozygous deletion in head and neck squamous cell carcinoma.
AB  - In tobacco-associated solid tumors, evidence suggests that the pattern of
      carcinogen exposure is related to the nature of somatic gene inactivation within
      crucial pathways, including the retinoblastoma (Rb) pathway. One somatic event in
      this pathway, homozygous deletion of the p16INK4A gene, is commonly observed in
      head and neck squamous cell carcinoma (HNSCC). Alcohol and tobacco are both well
      established risk factors for HNSCC but there has been little characterization of
      the relationship of exposure to these carcinogens and inactivation of the
      p16INK4A gene. Hypothesizing that p16INK4A homozygous deletion is associated with
      tobacco and alcohol exposure, we investigated 330 consecutive HNSCC tumors. The
      odds ratio (OR) for p16INK4A homozygous deletion among alcohol consumers in the
      upper tertile (>43 years used) was 5.2 [95% confidence interval (95% CI), 2.1
      12.8] as compared with those with < or = 43 years of alcohol consumption.
      Intensity of alcohol exposure, measured as average alcoholic drinks per week, was
      not associated with gene deletion. When we examined the distribution of duration
      of tobacco use, the OR for p16(INK4A) homozygous deletion was 1.3 (95% CI, 0.5
      3.0) and 1.9 (95% CI, 0.9-4.0) for 29 to 39 years and >39 years of tobacco
      smoking, respectively, as compared with those that smoked < or = 28 years. As in
      the case of alcohol use, intensity of tobacco exposure (measured as packs per
      day) was not associated with gene deletion. Hence, the duration of alcohol use
      and duration of smoking, but not intensity of either, significantly predicted
      p16(INK4A) homozygous deletion in HNSCC.

PMID- 16618780
TI  - Inhibition of p38 by vitamin D reduces interleukin-6 production in normal
      prostate cells via mitogen-activated protein kinase phosphatase 5: implications
      for prostate cancer prevention by vitamin D.
AB  - Although numerous studies have implicated vitamin D in preventing prostate
      cancer, the underlying mechanism(s) remains unclear. Using normal human prostatic
      epithelial cells, we examined the role of mitogen-activated protein kinase
      phosphatase 5 (MKP5) in mediating cancer preventive activities of vitamin D. Up
      regulation of MKP5 mRNA by 1,25-dihydroxyvitamin-D3 (1,25D) was dependent on the
      vitamin D receptor. We also identified a putative positive vitamin D response
      element within the MKP5 promoter that associated with the vitamin D receptor
      following 1,25D treatment. MKP5 dephosphorylates/inactivates the stress-activated
      protein kinase p38. Treatment of prostate cells with 1,25D inhibited p38
      phosphorylation, and MKP5 small interfering RNA blocked this effect. Activation
      of p38 and downstream production of interleukin 6 (IL-6) are proinflammatory.
      Inflammation and IL-6 overexpression have been implicated in the initiation and
      progression of prostate cancer. 1,25D pretreatment inhibited both UV- and tumor
      necrosis factor alpha-stimulated IL-6 production in normal cells via p38
      inhibition. Consistent with inhibition of p38, 1,25D decreased UV-stimulated IL-6
      mRNA stabilization. The ability of 1,25D to up-regulate MKP5 was maintained in
      primary prostatic adenocarcinoma cells but was absent in metastases-derived
      prostate cancer cell lines. The inability of 1,25D to regulate MKP5 in the
      metastasis-derived cancer cells suggests there may be selective pressure to
      eliminate key tumor suppressor functions of vitamin D during cancer progression.
      These studies reveal MKP5 as a mediator of p38 inactivation and decreased IL-6
      expression by 1,25D in primary prostatic cultures of normal and adenocarcinoma
      cells, implicating decreased prostatic inflammation as a potential mechanism for
      prostate cancer prevention by 1,25D.

PMID- 16618781
TI  - Genetic polymorphisms of interleukin-1B (IL-1B), IL-6, IL-8, and IL-10 and risk
      of prostate cancer.
AB  - Chronic intraprostatic inflammation is suspected to play a role in the
      pathogenesis of prostate cancer. Polymorphisms in cytokine genes can influence
      inflammation and immune response and may be related to the risk of prostate
      cancer. Four common single nucleotide polymorphisms (SNPs) in the genes encoding
      interleukin-1B (IL-1B), IL-6, and IL-8 were assessed in 503 prostate cancer cases
      and 652 controls, and three SNPs in IL-10 were assessed in an additional 817
      prostate cancer cases and 1,190 controls (for a total of 1,320 prostate cancer
      cases and 1,255 controls). Cases and controls were selected from the on-going
      Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial and were frequency
      matched on age, ethnicity, time-period since initial screening, and date of blood
      draw. Single-locus analyses were conducted using conditional logistic regression.
      In addition, we did a haplotype analysis for the three IL-10 SNPs tested.
      Overall, no associations were detected between the seven polymorphisms in the
      four cytokine genes examined in this study and prostate cancer risk. Further
      stratifying by use of nonsteroidal anti-inflammatory drugs did not modify the
      associations. Findings were similar for early or advanced prostate cancers.
      Similarly, we observed no association between the major IL-10 haplotypes and the
      risk of prostate cancer. At least seven common polymorphisms in genes of
      inflammatory cytokines IL-1B, IL-6, IL-8, and IL-10 do not seem to play a role in
      the risk of prostate cancer.

PMID- 16618782
TI  - Serum IgE, tumor epidermal growth factor receptor expression, and inherited
      polymorphisms associated with glioma survival.
AB  - In population-based glioma patients, we examined survival in relation to
      potentially pertinent constitutive polymorphisms, serologic factors, and tumor
      genetic and protein alterations in epidermal growth factor receptor (EGFR), MDM2,
      and TP53. Subjects were newly diagnosed adults residing in the San Francisco Bay
      Surveillance Epidemiology and End Results Area during 1991 to 1994 and 1997 to
      1999 with central neuropathology review (n = 873). Subjects provided blood for
      serologic studies of IgE and IgG to four herpes viruses and constitutive
      specimens for genotyping 22 polymorphisms in 13 genes (n = 471). We obtained 595
      of 697 astrocytic tumors for marker studies. We determined treatments, vital
      status, and other factors using registry, interview, medical record, and active
      follow-up data. Cox regressions for survival were adjusted for age, gender,
      ethnicity, study series, resection versus biopsy only, radiation, and
      chemotherapy. Using a stringent P < 0.001, glioma survival was associated with
      ERCC1 C8092A [hazard ratio (HR), 0.72; 95% confidence limits (95% CL), 0.60-0.86;
      P = 0.0004] and GSTT1 deletion (HR, 1.64; 95% CL, 1.25-2.16; P = 0.0004);
      glioblastoma patients with elevated IgE had 9 months longer survival than those
      with normal or borderline IgE levels (HR, 0.62; 95% CL, 0.47-0.82; P = 0.0007),
      and EGFR expression in anaplastic astrocytoma was associated with nearly 3-fold
      poorer survival (HR, 2.97; 95% CL, 1.70-5.19; P = 0.0001). Based on our and
      others' findings, we recommend further studies to (a) understand relationships of
      elevated IgE levels and other immunologic factors with improved glioblastoma
      survival potentially relevant to immunologic therapies and (b) determine which
      inherited ERCC1 variants or other variants in the 19q13.3 region influence
      survival. We also suggest that tumor EGFR expression be incorporated into
      clinical evaluation of anaplastic astrocytoma patients.

PMID- 16618783
TI  - Prevention of azoxymethane-induced colon cancer by combination of low doses of
      atorvastatin, aspirin, and celecoxib in F 344 rats.
AB  - Preclinical and clinical studies have provided evidence that aspirin, celecoxib,
      (cyclooxygenase-2 inhibitor), and statins (3-hydroxy-3-methylglutaryl CoA
      reductase inhibitors) inhibit colon carcinogenesis. Chronic use of high doses of
      these agents may induce side effects in ostensibly normal individuals. Combining
      low doses of agents may be an effective way to increase their efficacy and
      minimize toxicity. We assessed the efficacy of atorvastatin (lipitor), celecoxib,
      and aspirin, given individually at high dose levels and in combination at lower
      doses against azoxymethane-induced colon carcinogenesis, in male F 344 rats. One
      day after the last azoxymethane treatment (15 mg/kg body weight, s.c., once
      weekly for 2 weeks), groups of male F 344 rats were fed the AIN-76A diet or AIN
      76A diet containing 150 ppm atorvastatin, 600 ppm celecoxib, and 400 ppm aspirin,
      100 ppm atorvastatin + 300 ppm celecoxib, and 100 ppm atorvastatin + 200 ppm
      aspirin. Rats were killed 42 weeks later, and colon tumors were processed
      histopathologically and analyzed for cell proliferation and apoptosis
      immunohistochemically. Administration of these agents individually and in
      combination significantly suppressed the incidence and multiplicity of colon
      adenocarcinomas. Low doses of these agents in combination inhibited colon
      carcinogenesis more effectively than when they were given individually at higher
      doses. Inhibition of colon carcinogenesis by these agents is associated with the
      inhibition of cell proliferation and increase in apoptosis in colon tumors. These
      observations are of clinical significance because this can pave the way for the
      use of combinations of these agents in small doses against colon cancer.

PMID- 16618784
TI  - Stem cells in lung disease, repair, and the potential for therapeutic
      interventions: State-of-the-art and future challenges.

PMID- 16618785
TI  - Conditional control of gene expression in the respiratory epithelium: A
      cautionary note.

PMID- 16618786
TI  - Telomerase, myofibroblasts, and pulmonary fibrosis.

PMID- 16618787
TI  - Airway epithelium, inflammation, and mechanisms of disease: A tribute to Carol B.
      Basbaum.

PMID- 16618788
TI  - HGF and lung carcinoma: Don't forget neutrophils.

PMID- 16618789
TI  - T helper 1/T helper 2 cytokine imbalance in respiratory syncytial virus infection
      is associated with increased endogenous plasma cortisol.
AB  - OBJECTIVE: Cellular immunity has classically been described as the defense
      mechanism for viral infections. The development of cellular or humoral immune
      responses will depend on a repertoire of cytokines produced by numerous cells,
      including CD4+ and CD8+ T cells. These lymphocytes can be subdivided into 2
      subsets, T helper 1 (Th1) and Th2, on the basis of the cytokine profiles they
      synthesize. Type 1 T cells produce interferon gamma (IFN-gamma), an essential
      cytokine in the viral cell-mediated immune response. Th2 cells selectively
      produce interleukin 4 (IL-4) and IL-5 that participate in the development of
      humoral immunity and have a prominent role in immediate-type hypersensitivity. An
      imbalance in the Th1/Th2 cytokine immune response has been related to
      pathogenesis of the respiratory syncytial virus (RSV) bronchiolitis and to the
      severity of the infection. Glucocorticosteroids have a role in inhibiting the IFN
      gamma response, acting directly on T cells or indirectly through IL-12. In this
      way, an increase in plasma cortisol would induce a decrease in the Th1 products
      with the imbalance between Th1/Th2 cytokines and a shift to Th2 response. We
      hypothesized that there is a relationship among endogenous cortisol response in
      acute RSV infection, severity of illness, and decreased Th1 cytokine response.
      METHODS: We studied 42 infants under 12 months of age during an acute RSV
      infection. Twenty-one infants with a median age of 6 months had a severe illness
      and required hospitalization, whereas 21 with mild diseases with a median age of
      7 months were under ambulatory control. All of them had bronchial obstruction
      evidenced by wheezing and/or hyperinflation on chest radiograph and positive RSV
      antigen detected by indirect immunofluorescence in nasopharyngeal aspirates. The
      control group included 21 infants in good health matched by age and gender with
      median age of 6 months that required blood tests for minor surgery. They were
      evaluated during a non-RSV epidemic period. Heparinized blood was collected on
      enrollment from all participating children at 9 am for total leukocyte and
      differential cell count, determination of lymphocyte subsets, and for
      intracellular detection of cytokines in single cells; mononuclear cells were
      cultured to determine in the supernatant cytokine production. In addition, 1 mL
      of plasma was separated and kept frozen at -20 degrees C for cortisol assay. In
      the supernatant of the cultured peripheral blood mononuclear cells (PBMCs), we
      quantified IL-12, IFN-gamma, IL-4, IL-5, and IL-10. Lymphocyte phenotypes and
      CD4+ and CD8+ T cells with intracellular IL-4, IL-10, and IFN-gamma were analyzed
      by triple-color immunofluorescence of single cells on a FACScan flow cytometer.
      RESULTS: Infants with severe illness had significantly higher plasma cortisol
      levels than infants with mild disease, and in both groups of infected infants,
      those were higher than in the control group. A significantly decreased IL-12 and
      IFN-gamma production by PBMCs and a fall in the percentage of CD4+ T cells
      expressing IFN-gamma were observed only in the severely affected infants. IL-12
      concentrations were 2 pg/mL in severe illness versus 13 pg/mL in mildly infected
      infants and 12 pg/mL in controls. PBMCs from infants with severe illness produced
      less IFN-gamma than mildly infected infants and than controls when compared with
      severe illness. No differences between the 3 groups of infants were observed
      during the acute phase of the disease for IL-4, IL-5, and IL-10. IL-12 and IFN
      gamma production had an inverse correlation with plasma cortisol levels. During
      severe RSV bronchiolitis, infants developed lymphopenia, and significantly lower
      eosinophil counts and percentages and absolute counts of CD4+ and CD8+ T cells.
      Eighty days postinfection, all values had returned to normal levels. CONCLUSIONS:
      In this study, we demonstrate that during the acute phase of RSV infection, there
      is an increase in the level of plasma cortisol that is parallel to the decrease
      in IL-12 and IFN-gamma production. These findings suggest an association between
      increased plasma cortisol and a decreased Th1-type response. The increase in
      plasma cortisol was greater in infants with the more severe symptomatology in
      association with a lower level of IL-12 and IFN-gamma production. The potential
      causative role of endogenous cortisol in the imbalance of the Th1/Th2 response
      observed during severe RSV infection requires additional investigation. Our
      results suggest that the immunologic changes observed in the more severely ill
      patients may be partially explained by the increased levels of plasma cortisol.
      This finding should be taken into consideration when systemic steroids are
      prescribed to infants infected with the RSV because there is still controversy
      regarding the efficacy of systemic steroid use in severe bronchiolitis.

PMID- 16618790
TI  - The International Liaison Committee on Resuscitation (ILCOR) consensus on science
      with treatment recommendations for pediatric and neonatal patients: pediatric
      basic and advanced life support.
AB  - This publication contains the pediatric and neonatal sections of the 2005
      International Consensus on Cardiopulmonary Resuscitation and Emergency
      Cardiovascular Care Science With Treatment Recommendations (COSTR). The consensus
      process that produced this document was sponsored by the International Liaison
      Committee on Resuscitation (ILCOR). ILCOR was formed in 1993 and consists of
      representatives of resuscitation councils from all over the world. Its mission is
      to identify and review international science and knowledge relevant to
      cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) and
      to generate consensus on treatment recommendations. ECC includes all responses
      necessary to treat life-threatening cardiovascular and respiratory events. The
      COSTR document presents international consensus statements on the science of
      resuscitation. ILCOR member organizations are each publishing resuscitation
      guidelines that are consistent with the science in this consensus document, but
      they also take into consideration geographic, economic, and system differences in
      practice and the regional availability of medical devices and drugs. The American
      Heart Association (AHA) pediatric and the American Academy of Pediatrics/AHA
      neonatal sections of the resuscitation guidelines are reprinted in this issue of
      Pediatrics (see pages e978-e988). The 2005 evidence evaluation process began
      shortly after publication of the 2000 International Guidelines for CPR and ECC.
      The process included topic identification, expert topic review, discussion and
      debate at 6 international meetings, further review, and debate within ILCOR
      member organizations and ultimate approval by the member organizations, an
      Editorial Board, and peer reviewers. The complete COSTR document was published
      simultaneously in Circulation (International Liaison Committee on Resuscitation.
      2005 International Consensus on Cardiopulmonary Resuscitation and Emergency
      Cardiovascular Care Science With Treatment Recommendations. Circulation.
      2005;112(suppl):73-90) and Resuscitation (International Liaison Committee on
      Resuscitation. 2005 International Consensus Conference on Cardiopulmonary
      Resuscitation and Emergency Cardiovascular Care Science With Treatment
      Recommendations. Resuscitation. 2005;67:271-291). Readers are encouraged to
      review the 2005 COSTR document in its entirety. It can be accessed through the
      CPR and ECC link at the AHA Web site: www.americanheart.org. The complete
      publication represents the largest evaluation of resuscitation literature ever
      published and contains electronic links to more detailed information about the
      international collaborative process. To organize the evidence evaluation, ILCOR
      representatives established 6 task forces: basic life support, advanced life
      support, acute coronary syndromes, pediatric life support, neonatal life support,
      and an interdisciplinary task force to consider overlapping topics such as
      educational issues. The AHA established additional task forces on stroke and, in
      collaboration with the American Red Cross, a task force on first aid. Each task
      force identified topics requiring evaluation and appointed international experts
      to review them. A detailed worksheet template was created to help the experts
      document their literature review, evaluate studies, determine levels of evidence,
      develop treatment recommendations, and disclose conflicts of interest. Two
      evidence evaluation experts reviewed all worksheets and assisted the worksheet
      reviewers to ensure that the worksheets met a consistently high standard. A total
      of 281 experts completed 403 worksheets on 275 topics, reviewing more than 22000
      published studies. In December 2004 the evidence review and summary portions of
      the evidence evaluation worksheets, with worksheet author conflict of interest
      statements, were posted on the Internet at www.C2005.org, where readers can
      continue to access them. Journal advertisements and e-mails invited public
      comment. Two hundred forty-nine worksheet authors (141 from the United States and
      108 from 17 other countries) and additional invited experts and reviewers
      attended the 2005 International Consensus Conference for presentation,
      discussion, and debate of the evidence. All 380 participants at the conference
      received electronic copies of the worksheets. Internet access was available to
      all conference participants during the conference to facilitate real-time
      verification of the literature. Expert reviewers presented topics in plenary,
      concurrent, and poster conference sessions with strict adherence to a novel and
      rigorous conflict of interest process. Presenters and participants then debated
      the evidence, conclusions, and draft summary statements. Wording of science
      statements and treatment recommendations was refined after further review by
      ILCOR member organizations and the international editorial board. This format
      ensured that the final document represented a truly international consensus
      process. The COSTR manuscript was ultimately approved by all ILCOR member
      organizations and by an international editorial board. The AHA Science Advisory
      and Coordinating Committee and the editor of Circulation obtained peer reviews of
      this document before it was accepted for publication. The most important changes
      in recommendations for pediatric resuscitation since the last ILCOR review in
      2000 include: Increased emphasis on performing high quality CPR: "Push hard, push
      fast, minimize interruptions of chest compression; allow full chest recoil, and
      don't provide excessive ventilation" Recommended chest compression-ventilation
      ratio: For lone rescuers with victims of all ages: 30:2 For health care providers
      performing 2-rescuer CPR for infants and children: 15:2 (except 3:1 for neonates)
      Either a 2- or 1-hand technique is acceptable for chest compressions in children
      Use of 1 shock followed by immediate CPR is recommended for each defibrillation
      attempt, instead of 3 stacked shocks Biphasic shocks with an automated external
      defibrillator (AED) are acceptable for children 1 year of age. Attenuated shocks
      using child cables or activation of a key or switch are recommended in children
      <8 years old. Routine use of high-dose intravenous (IV) epinephrine is no longer
      recommended. Intravascular (IV and intraosseous) route of drug administration is
      preferred to the endotracheal route. Cuffed endotracheal tubes can be used in
      infants and children provided correct tube size and cuff inflation pressure are
      used. Exhaled CO2 detection is recommended for confirmation of endotracheal tube
      placement. Consider induced hypothermia for 12 to 24 hours in patients who remain
      comatose following resuscitation. Some of the most important changes in
      recommendations for neonatal resuscitation since the last ILCOR review in 2000
      include less emphasis on using 100% oxygen when initiating resuscitation, de
      emphasis of the need for routine intrapartum oropharyngeal and nasopharyngeal
      suctioning for infants born to mothers with meconium staining of amniotic fluid,
      proven value of occlusive wrapping of very low birth weight infants <28 weeks'
      gestation to reduce heat loss, preference for the IV versus the endotracheal
      route for epinephrine, and an increased emphasis on parental autonomy at the
      threshold of viability. The scientific evidence supporting these recommendations
      is summarized in the neonatal document (see pages e978-e988).

PMID- 16618791
TI  - The International Liaison Committee on Resuscitation (ILCOR) consensus on science
      with treatment recommendations for pediatric and neonatal patients: neonatal
      resuscitation.

PMID- 16618792
TI  - Fas-positive T cells regulate the resolution of airway inflammation in a murine
      model of asthma.
AB  - Persistent airway inflammation, mucus production, and airway hyperreactivity are
      the major contributors to the frequency and severity of asthma. Why lung
      inflammation persists in asthmatics remains unclear. It has been proposed that
      Fas-mediated apoptosis of inflammatory cells is a fundamental mechanism involved
      in the resolution of eosinophilic airway inflammation. Because infiltrating
      eosinophils are highly sensitive to Fas-mediated apoptosis, it has been presumed
      that direct ligation of Fas on eosinophils is involved. Here, we utilize adoptive
      transfers of T cells to demonstrate that the delayed resolution of eosinophilia
      in Fas-deficient mice is a downstream effect of Fas deficiency on T cells, not
      eosinophils. Interestingly, the mice that received Fas-deficient T cells, but not
      the controls, developed a persistent phase of inflammation that failed to resolve
      even 6 wk after the last challenge. This persistent phase correlated with
      decreased interferon (IFN)gamma production by Fas-deficient T cells and could be
      reproduced with adoptive transfer of IFNgamma-deficient T cells. These data
      demonstrate that Fas deficiency on T cells is sufficient for the development of
      long-term allergic airway disease in mice and implies that deregulation of death
      receptors such as Fas on human T cells could be an important factor in the
      development and/or chronic nature of asthma.

PMID- 16618793
TI  - Cholesterol deficiency in a mouse model of Smith-Lemli-Opitz syndrome reveals
      increased mast cell responsiveness.
AB  - Mutation of the 3beta-hydroxysterol delta7-reductase gene (Dhcr7-/-) results in
      Smith-Lemli-Opitz syndrome (SLOS). Patients, and genetically altered mice, are
      unable to produce cholesterol and accumulate 7-dehydrocholesterol (DHC) in serum
      and tissue. This causes multiple growth and developmental abnormalities as well
      as immune system anomalies including allergy. Because cholesterol is a key
      component of liquid-ordered membranes (lipid rafts) and these domains have been
      implicated in regulating mast cell activation, we examined whether mast cell
      responsiveness is altered in this model. Mast cells derived from Dhcr7-/- mice
      (DHCR KO) showed constitutive cytokine production and hyper-degranulation after
      stimulation of the high affinity IgE receptor (Fc epsilonRI). DHCR KO mast cells,
      but not wild-type mast cells, accumulated DHC in lipid rafts. DHC partially
      disrupted lipid raft stability and displaced Lyn kinase protein and activity from
      lipid rafts. This led to down-regulation of some Lyn-dependent signaling events
      but increased Fyn kinase activity and Akt phosphorylation. The Lyn-dependent
      phosphorylation of Csk-binding protein, which negatively regulates Fyn activity,
      was decreased. This phenotype reproduces some of the characteristics of Lyn-null
      mast cells, which also demonstrate hyper-degranulation. These findings provide
      the first evidence of lipid raft dysfunction in SLOS and may explain the observed
      association of allergy with SLOS.

PMID- 16618794
TI  - Platelets secrete stromal cell-derived factor 1alpha and recruit bone marrow
      derived progenitor cells to arterial thrombi in vivo.
AB  - The accumulation of smooth muscle and endothelial cells is essential for
      remodeling and repair of injured blood vessel walls. Bone marrow-derived
      progenitor cells have been implicated in vascular repair and remodeling; however,
      the mechanisms underlying their recruitment to the site of injury remain elusive.
      Here, using real-time in vivo fluorescence microscopy, we show that platelets
      provide the critical signal that recruits CD34+ bone marrow cells and c-Kit+ Sca
      1+ Lin- bone marrow-derived progenitor cells to sites of vascular injury.
      Correspondingly, specific inhibition of platelet adhesion virtually abrogated the
      accumulation of both CD34+ and c-Kit+ Sca-1+ Lin- bone marrow-derived progenitor
      cells at sites of endothelial disruption. Binding of bone marrow cells to
      platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly,
      we found that activated platelets secrete the chemokine SDF-1alpha, thereby
      supporting further primary adhesion and migration of progenitor cells. These
      findings establish the platelet as a major player in the initiation of vascular
      remodeling, a process of fundamental importance for vascular repair and
      pathological remodeling after vascular injury.

PMID- 16618795
TI  - Comparative study of ortho- and meta-nitrated inhibitors of catechol-O
      methyltransferase: interactions with the active site and regioselectivity of O
      methylation.
AB  - In this work, we present a comparative case study of "ortho-" and "meta-nitrated"
      catecholic inhibitors of catechol-O-methyltransferase (COMT), with regard to
      their interaction with the catalytic site of the enzyme and the in vitro
      regioselective formation of their mono-O-methyl ether metabolites. In particular,
      the effects of altering the attachment position of the inhibitors' side-chain
      substituent, within the classic nitrocatechol pharmacophore, were investigated.
      For this purpose, we compared two simple regioisomeric nitrocatechol-type
      inhibitors of COMT, BIA 3-228 and BIA 8-176, which contain the benzoyl
      substituent attached at the meta and ortho positions, respectively, relative to
      the nitro group. The two compounds were slowly O-methylated by COMT in vitro, but
      the particular substitution pattern of each compound was shown to have a profound
      impact on the regioselectivity of their O-methylation. To provide a plausible
      interpretation of these results, a comprehensive analysis of the protein
      inhibitor interactions and of the relative chemical susceptibility to O
      methylation of the catechol hydroxyl groups was performed by means of docking
      simulations and ab initio molecular orbital calculations. The major structural
      and chemical factors that determine the enzyme regioselectivity of O-methylation
      were identified, and the X-ray structure of the complex of COMT with S-adenosyl-l
      methionine and BIA 8-176 is herein disclosed. This is the first reported
      structure of the soluble form of COMT complexed with a nitrocatecholic inhibitor
      having a bulky substituent group in adjacent position (ortho) to the nitro group.
      Structural and dynamic aspects of this complex are analyzed and discussed, in the
      context of the present study.

PMID- 16618796
TI  - Inhibition of human tyrosyl-DNA phosphodiesterase by aminoglycoside antibiotics
      and ribosome inhibitors.
AB  - DNA topoisomerase I (Top1) is the target of camptothecin, and novel Top1
      inhibitors are in development as anticancer agents. Top1 inhibitors damage DNA by
      trapping covalent complexes between the Top1 catalytic tyrosine and the 3'-end of
      the broken DNA. Tyrosyl-DNA phosphodiesterase (Tdp1) can repair Top1-DNA covalent
      complexes by hydrolyzing the tyrosyl-DNA bond. Inhibiting Tdp1 has the potential
      to enhance the anticancer activity of Top1 inhibitors
      (http://discover.nci.nih.gov/pommier/pommier.htm) and to act as antiproliferative
      agents. In the present study, we report that neomycin inhibits Tdp1 more
      effectively than the related aminoglycosides paromomycin and lividomycin A.
      Inhibition of Tdp1 by neomycin is observed both with single- and double-stranded
      substrates but is slightly stronger with duplex DNA, which is different from
      aclarubicin, which only inhibits Tdp1 with the double-stranded substrate.
      Inhibition by neomycin can be overcome with excess Tdp1 and is greatest at low
      pH. To our knowledge, aminoglycoside antibiotics and the ribosome inhibitors
      thiostrepton, clindamycin-2-phosphate, and puromycin are the first reported
      pharmacological Tdp1 inhibitors.

PMID- 16618797
TI  - Requirement of clathrin heavy chain for p53-mediated transcription.
AB  - The p53 protein is a transcription factor that activates various genes
      responsible for growth arrest and/or apoptosis in response to DNA damage. Here,
      we report that clathrin heavy chain (CHC) binds to p53 and contributes to p53
      mediated transcription. CHC is known to be a cytosolic protein that functions as
      a vesicle transporter. We found, however, that CHC exists not only in cytosol but
      also in nuclei. CHC expression enhances p53-dependent transactivation, whereas
      the reduction of CHC expression by RNA interference (RNAi) attenuates its
      transcriptional activity. Moreover, CHC binds to the p53-responsive promoter in
      vivo and stabilizes p53-p300 interaction to promote p53-mediated transcription.
      Thus, nuclear CHC is required for the transactivation of p53 target genes and
      plays a distinct role from clathrin-mediated endocytosis.

PMID- 16618798
TI  - Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription.
AB  - We investigated the role of SIRT7, one of the seven members of the mammalian
      sirtuin family. We show that SIRT7 is a widely expressed nucleolar protein that
      is associated with active rRNA genes (rDNA), where it interacts with RNA
      polymerase I (Pol I) as well as with histones. Overexpression of SIRT7 increases
      Pol I-mediated transcription, whereas knockdown of SIRT7 or inhibition of the
      catalytic activity results in decreased association of Pol I with rDNA and a
      reduction of Pol I transcription. Depletion of SIRT7 stops cell proliferation and
      triggers apoptosis. Our findings suggest that SIRT7 is a positive regulator of
      Pol I transcription and is required for cell viability in mammals.

PMID- 16618799
TI  - Feedback control of morphogenesis in fungi by aromatic alcohols.
AB  - Many fungi undergo a developmental transition from a unicellular yeast form to an
      invasive filamentous form in response to environmental cues. Here we describe a
      quorum signaling pathway that links environmental sensing to morphogenesis in
      Saccharomyces cerevisiae. Saccharomyces cells secrete aromatic alcohols that
      stimulate morphogenesis by inducing the expression of FLO11 through a Tpk2p
      dependent mechanism. Mutants defective in synthesis of these alcohols show
      reduced filamentous growth, which is partially suppressed by the addition of
      these aromatic alcohols. The production of these auto signaling alcohols is
      regulated by nitrogen: High ammonia restricts it by repressing the expression of
      their biosynthetic pathway, whereas nitrogen-poor conditions activate it.
      Moreover, the production of these aromatic alcohols is controlled by cell density
      and subjected to positive feedback regulation, which requires the transcription
      factor Aro80p. These interactions define a quorum-sensing circuit that allows
      Saccharomyces to respond to both cell density and the nutritional state of the
      environment. These same autoregulatory molecules do not evoke the morphological
      switch in Candida albicans, suggesting that these molecular signals are species
      specific.

PMID- 16618800
TI  - A Polycomb group protein complex with sequence-specific DNA-binding and selective
      methyl-lysine-binding activities.
AB  - Polycomb response elements (PREs) are specific cis-regulatory sequences needed
      for transcriptional repression of HOX and other target genes by Polycomb group
      (PcG) proteins. Among the many PcG proteins known in Drosophila, Pho is the only
      sequence-specific DNA-binding protein. To gain insight into the function of Pho,
      we purified Pho protein complexes from Drosophila embryos and found that Pho
      exists in two distinct protein assemblies: a Pho-dINO80 complex containing the
      Drosophila INO80 nucleosome-remodeling complex, and a Pho-repressive complex
      (PhoRC) containing the uncharacterized gene product dSfmbt. Analysis of PhoRC
      reveals that dSfmbt is a novel PcG protein that is essential for HOX gene
      repression in Drosophila. PhoRC is bound at HOX gene PREs in vivo, and this
      targeting strictly depends on Pho-binding sites. Characterization of dSfmbt
      protein shows that its MBT repeats have unique discriminatory binding activity
      for methylated lysine residues in histones H3 and H4; the MBT repeats bind mono-
      and di-methylated H3-K9 and H4-K20 but fail to interact with these residues if
      they are unmodified or tri-methylated. Our results establish PhoRC as a novel
      Drosophila PcG protein complex that combines DNA-targeting activity (Pho) with a
      unique modified histone-binding activity (dSfmbt). We propose that PRE-tethered
      PhoRC selectively interacts with methylated histones in the chromatin flanking
      PREs to maintain a Polycomb-repressed chromatin state.

PMID- 16618802
TI  - Downstream control of upstream open reading frames.

PMID- 16618801
TI  - Genome-wide mapping of Polycomb target genes unravels their roles in cell fate
      transitions.
AB  - The Polycomb group (PcG) proteins form chromatin-modifying complexes that are
      essential for embryonic development and stem cell renewal and are commonly
      deregulated in cancer. Here, we identify their target genes using genome-wide
      location analysis in human embryonic fibroblasts. We find that Polycomb
      Repressive Complex 1 (PRC1), PRC2, and tri-methylated histone H3K27 co-occupy
      >1000 silenced genes with a strong functional bias for embryonic development and
      cell fate decisions. We functionally identify 40 genes derepressed in human
      embryonic fibroblasts depleted of the PRC2 components (EZH2, EED, SUZ12) and the
      PRC1 component, BMI-1. Interestingly, several markers of osteogenesis,
      adipogenesis, and chrondrogenesis are among these genes, consistent with the
      mesenchymal origin of fibroblasts. Using a neuronal model of differentiation, we
      delineate two different mechanisms for regulating PcG target genes. For genes
      activated during differentiation, PcGs are displaced. However, for genes
      repressed during differentiation, we paradoxically find that they are already
      bound by the PcGs in nondifferentiated cells despite being actively transcribed.
      Our results are consistent with the hypothesis that PcGs are part of a
      preprogrammed memory system established during embryogenesis marking certain key
      genes for repressive signals during subsequent developmental and differentiation
      processes.

PMID- 16618803
TI  - Polar auxin transport and patterning: grow with the flow.

PMID- 16618804
TI  - In vivo beta1 integrin function requires phosphorylation-independent regulation
      by cytoplasmic tyrosines.
AB  - Integrins are heterodimeric adhesion receptors associated with bidirectional
      signaling. In vitro studies support a role for the binding of evolutionarily
      conserved tyrosine motifs (NPxY) in the beta integrin cytoplasmic tail to
      phosphotyrosine-binding (PTB) domain-containing proteins, an interaction proposed
      to be dynamically regulated by tyrosine phosphorylation. Here we show that
      replacement of both beta1 integrin cytoplasmic tyrosines with alanines, resulting
      in the loss of all PTB domain interaction, causes complete loss of beta1 integrin
      function in vivo. In contrast, replacement of beta1 integrin cytoplasmic
      tyrosines with phenylalanines, a mutation that prevents tyrosine phosphorylation,
      conserves in vivo integrin function. These results have important implications
      for the molecular mechanism and regulation of integrin function.

PMID- 16618805
TI  - Repression of Flt3 by Pax5 is crucial for B-cell lineage commitment.
AB  - Early B-lymphopoiesis requires the growth-factor receptors, IL-7R and Flt3, and
      the activity of a number of transcription factors. One factor, Pax5, is required
      for commitment to the B-cell lineage, although the molecular mechanism by which
      this occurs is unknown. We demonstrate here that an important function of Pax5 is
      to repress Flt3 transcription in B-cell progenitors, as Pax5-deficient pro-B
      cells express abundant Flt3 that is rapidly silenced upon the reintroduction of
      Pax5, whereas enforced expression of Flt3 in wild-type progenitors significantly
      impairs B-cell development. These findings demonstrate that the repression of
      Flt3 by Pax5 is essential for normal B-lymphopoiesis.

PMID- 16618806
TI  - Two-stage mechanism for activation of the DNA replication checkpoint kinase Cds1
      in fission yeast.
AB  - The DNA replication checkpoint is a complex signal transduction pathway, present
      in all eukaryotic cells, that functions to maintain genomic integrity and cell
      viability when DNA replication is perturbed. In Schizosaccharomyces pombe the
      major effector of the replication checkpoint is the protein kinase Cds1.
      Activation of Cds1 is known to require the upstream kinase Rad3 and the mediator
      Mrc1, but the biochemical mechanism of activation is not well understood. We
      report that the replication checkpoint is activated in two stages. In the first
      stage, Mrc1 recruits Cds1 to stalled replication forks by interactions between
      the FHA domain of Cds1 and specific phosphorylated Rad3 consensus sites in Mrc1.
      Cds1 is then primed for activation by Rad3-dependent phosphorylation. In the
      second stage, primed Cds1 molecules dimerize via phospho-specific interactions
      mediated by the FHA domains and are activated by autophosphorylation. This two
      stage activation mechanism for the replication checkpoint allows for rapid
      activation with a high signal-to-noise ratio.

PMID- 16618807
TI  - Control of leaf vascular patterning by polar auxin transport.
AB  - The formation of the leaf vascular pattern has fascinated biologists for
      centuries. In the early leaf primordium, complex networks of procambial cells
      emerge from homogeneous subepidermal tissue. The molecular nature of the
      underlying positional information is unknown, but various lines of evidence
      implicate gradually restricted transport routes of the plant hormone auxin in
      defining sites of procambium formation. Here we show that a crucial member of the
      AtPIN family of auxin-efflux-associated proteins, AtPIN1, is expressed prior to
      pre-procambial and procambial cell fate markers in domains that become restricted
      toward sites of procambium formation. Subcellular AtPIN1 polarity indicates that
      auxin is directed to distinct "convergence points" in the epidermis, from where
      it defines the positions of major veins. Integrated polarities in all emerging
      veins indicate auxin drainage toward pre-existing veins, but veins display
      divergent polarities as they become connected at both ends. Auxin application and
      transport inhibition reveal that convergence point positioning and AtPIN1
      expression domain dynamics are self-organizing, auxin-transport-dependent
      processes. We derive a model for self-regulated, reiterative patterning of all
      vein orders and postulate at its onset a common epidermal auxin-focusing
      mechanism for major-vein positioning and phyllotactic patterning.

PMID- 16618808
TI  - Cross-regulation between Notch and p63 in keratinocyte commitment to
      differentiation.
AB  - Notch signaling promotes commitment of keratinocytes to differentiation and
      suppresses tumorigenesis. p63, a p53 family member, has been implicated in
      establishment of the keratinocyte cell fate and/or maintenance of epithelial self
      renewal. Here we show that p63 expression is suppressed by Notch1 activation in
      both mouse and human keratinocytes through a mechanism independent of cell cycle
      withdrawal and requiring down-modulation of selected interferon-responsive genes,
      including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the
      ability of Notch1 to restrict growth and promote differentiation. p63 functions
      as a selective modulator of Notch1-dependent transcription and function, with the
      Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk
      between Notch and p63 is involved in the balance between keratinocyte self
      renewal and differentiation.

PMID- 16618809
TI  - Synaptotagmin IV is necessary for the maturation of secretory granules in PC12
      cells.
AB  - In neuroendocrine PC12 cells, immature secretory granules (ISGs) mature through
      homotypic fusion and membrane remodeling. We present evidence that the ISG
      localized synaptotagmin IV (Syt IV) is involved in ISG maturation. Using an in
      vitro homotypic fusion assay, we show that the cytoplasmic domain (CD) of Syt IV,
      but not of Syt I, VII, or IX, inhibits ISG homotypic fusion. Moreover, Syt IV CD
      binds specifically to ISGs and not to mature secretory granules (MSGs), and Syt
      IV binds to syntaxin 6, a SNARE protein that is involved in ISG maturation. ISG
      homotypic fusion was inhibited in vivo by small interfering RNA-mediated
      depletion of Syt IV. Furthermore, the Syt IV CD, as well as Syt IV depletion,
      reduces secretogranin II (SgII) processing by prohormone convertase 2 (PC2). PC2
      is found mostly in the proform, suggesting that activation of PC2 is also
      inhibited. Granule formation, and the sorting of SgII and PC2 from the trans
      Golgi network into ISGs and MSGs, however, is not affected. We conclude that Syt
      IV is an essential component for secretory granule maturation.

PMID- 16618810
TI  - Caspases leave the beaten track: caspase-mediated activation of NF-kappaB.
AB  - The proteolytic activity of the cysteinyl aspartate-specific proteases, named
      caspases, mainly connotes their central role in apoptosis and inflammation. In
      this review we report on recent data on the role of caspases in the activation of
      nuclear factor kappaB (NF-kappaB), a transcription factor that fulfils a central
      role in innate and adaptive immunity, in cellular stress responses and in the
      induction of anti-apoptotic factors. Two different mechanisms by which caspases
      activate the NF-kappaB pathway are discussed.

PMID- 16618811
TI  - Spatial organization of the mammalian genome surveillance machinery in response
      to DNA strand breaks.
AB  - We show that DNA double-strand breaks (DSBs) induce complex
      subcompartmentalization of genome surveillance regulators. Chromatin marked by
      gamma-H2AX is occupied by ataxia telangiectasia-mutated (ATM) kinase, Mdc1, and
      53BP1. In contrast, repair factors (Rad51, Rad52, BRCA2, and FANCD2), ATM and Rad
      3-related (ATR) cascade (ATR, ATR interacting protein, and replication protein
      A), and the DNA clamp (Rad17 and -9) accumulate in subchromatin microcompartments
      delineated by single-stranded DNA (ssDNA). BRCA1 and the Mre11-Rad50-Nbs1 complex
      interact with both of these compartments. Importantly, some core DSB regulators
      do not form cytologically discernible foci. These are further subclassified to
      proteins that connect DSBs with the rest of the nucleus (Chk1 and -2), that
      assemble at unprocessed DSBs (DNA-PK/Ku70), and that exist on chromatin as
      preassembled complexes but become locally modified after DNA damage (Smc1/Smc3).
      Finally, checkpoint effectors such as p53 and Cdc25A do not accumulate at DSBs at
      all. We propose that subclassification of DSB regulators according to their
      residence sites provides a useful framework for understanding their involvement
      in diverse processes of genome surveillance.

PMID- 16618812
TI  - JNK1 phosphorylation of SCG10 determines microtubule dynamics and axodendritic
      length.
AB  - c-Jun NH(2)-terminal kinases (JNKs) are essential during brain development, when
      they regulate morphogenic changes involving cell movement and migration. In the
      adult, JNK determines neuronal cytoarchitecture. To help uncover the molecular
      effectors for JNKs in these events, we affinity purified JNK-interacting proteins
      from brain. This revealed that the stathmin family microtubule-destabilizing
      proteins SCG10, SCLIP, RB3, and RB3' interact tightly with JNK. Furthermore,
      SCG10 is also phosphorylated by JNK in vivo on sites that regulate its
      microtubule depolymerizing activity, serines 62 and 73. SCG10-S73 phosphorylation
      is significantly decreased in JNK1-/- cortex, indicating that JNK1 phosphorylates
      SCG10 in developing forebrain. JNK phosphorylation of SCG10 determines
      axodendritic length in cerebrocortical cultures, and JNK site-phosphorylated
      SCG10 colocalizes with active JNK in embryonic brain regions undergoing neurite
      elongation and migration. We demonstrate that inhibition of cytoplasmic JNK and
      expression of SCG10-62A/73A both inhibited fluorescent tubulin recovery after
      photobleaching. These data suggest that JNK1 is responsible for regulation of
      SCG10 depolymerizing activity and neurite elongation during brain development.

PMID- 16618813
TI  - Direct requirement for Xmus101 in ATR-mediated phosphorylation of Claspin bound
      Chk1 during checkpoint signaling.
AB  - TopBP1-like proteins, which include Xenopus laevis Xmus101, are required for DNA
      replication and have been linked to replication checkpoint control. A direct role
      for TopBP1/Mus101 in checkpoint control has been difficult to prove, however,
      because of the requirement for replication in generating the DNA structures that
      activate the checkpoint. Checkpoint activation occurs in X. laevis egg extracts
      upon addition of an oligonucleotide duplex (AT70). We show that AT70 bypasses the
      requirement for replication in checkpoint activation. We take advantage of this
      replication-independent checkpoint system to determine the role of Xmus101 in the
      checkpoint. We find that Xmus101 is essential for AT70-mediated checkpoint
      signaling and that it functions to promote phosphorylation of Claspin bound Chk1
      by the ataxia-telangiectasia and Rad-3-related (ATR) protein kinase. We also
      identify a separation-of-function mutant of Xmus101. In extracts expressing this
      mutant, replication of sperm chromatin occurs normally; however, the checkpoint
      response to stalled replication forks fails. These data demonstrate that Xmus101
      functions directly during signal relay from ATR to Chk1.

PMID- 16618815
TI  - Direct in vivo monitoring of sarcoplasmic reticulum Ca2+ and cytosolic cAMP
      dynamics in mouse skeletal muscle.
AB  - Skeletal muscle contraction depends on the release of Ca(2+) from the
      sarcoplasmic reticulum (SR), but the dynamics of the SR free Ca(2+) concentration
      ([Ca(2+)](SR)), its modulation by physiological stimuli such as catecholamines,
      and the concomitant changes in cAMP handling have never been directly determined.
      We used two-photon microscopy imaging of GFP-based probes expressed in mouse
      skeletal muscles to monitor, for the first time in a live animal, the dynamics of
      [Ca(2+)](SR) and cAMP. Our data, which were obtained in highly physiological
      conditions, suggest that free [Ca(2+)](SR) decreases by approximately 50 microM
      during single twitches elicited through nerve stimulation. We also demonstrate
      that cAMP levels rise upon beta-adrenergic stimulation, leading to an increased
      efficacy of the Ca(2+) release/reuptake cycle during motor nerve stimulation.

PMID- 16618814
TI  - Stepwise RNP assembly at the site of H/ACA RNA transcription in human cells.
AB  - Mammalian H/ACA RNPs are essential for ribosome biogenesis, premessenger RNA
      splicing, and telomere maintenance. These RNPs consist of four core proteins and
      one RNA, but it is not known how they assemble. By interrogating the site of
      H/ACA RNA transcription, we dissected their biogenesis in single cells and
      delineated the role of the non-core protein NAF1 in the process. NAF1 and all of
      the core proteins except GAR1 are recruited to the site of transcription. NAF1
      binds one of the core proteins, NAP57, and shuttles between nucleus and
      cytoplasm. Both proteins are essential for stable H/ACA RNA accumulation. NAF1
      and GAR1 bind NAP57 competitively, suggesting a sequential interaction. Our
      analyses indicate that NAF1 binds NAP57 and escorts it to the nascent H/ACA RNA
      and that GAR1 then replaces NAF1 to yield mature H/ACA RNPs in Cajal bodies and
      nucleoli.

PMID- 16618816
TI  - Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal
      antiinflammatory drugs and risk of acute myocardial infarction.
AB  - BACKGROUND: The cardiovascular safety of cyclooxygenase (COX)-2-selective
      nonsteroidal antiinflammatory drugs (NSAIDs) has come under scrutiny after the
      withdrawal of rofecoxib and halting of the Adenoma Prevention with Celecoxib
      trial. Whether the newer second-generation COX-2 inhibitors (etoricoxib,
      valdecoxib) also increase the cardiovascular risk is unknown. METHODS AND
      RESULTS: We performed a nested case-control study in a cohort of 486,378 persons
      registered within the United Kingdom General Practice Research Database with at
      least 1 prescription of an NSAID between June 1, 2000, and October 31, 2004. A
      total of 3643 cases with acute myocardial infarction (AMI) were matched to 13,918
      controls on age, sex, year of cohort entry, and general practice. Rate ratios
      (RRs) of AMI associated with use of COX-2-selective and -nonselective NSAIDs were
      calculated. Current use of etoricoxib was associated with a 2.09-fold (95%
      confidence interval [CI], 1.10 to 3.97) risk of AMI compared with no use of
      NSAIDs during the prior year. Current use of rofecoxib (RR=1.29; 95% CI, 1.02 to
      1.63), celecoxib (RR=1.56; 95% CI, 1.22 to 2.00), and diclofenac (RR=1.37; 95%
      CI, 1.17 to 1.59) also significantly increased the AMI risk. For current use of
      valdecoxib, the RR was 4.60 (95% CI, 0.61 to 34.51). RRs appeared to increase
      with higher daily doses of COX-2 inhibitors and were also increased in patients
      without major cardiovascular risk factors. CONCLUSIONS: Our study supports the
      hypothesis that the elevated risk of AMI is a class effect of COX-2 inhibitors.
      The increase in risk appears to be dose dependent, but further data are needed to
      verify this observation.

PMID- 16618817
TI  - Myocardial structure and function differ in systolic and diastolic heart failure.
AB  - BACKGROUND: To support the clinical distinction between systolic heart failure
      (SHF) and diastolic heart failure (DHF), left ventricular (LV) myocardial
      structure and function were compared in LV endomyocardial biopsy samples of
      patients with systolic and diastolic heart failure. METHODS AND RESULTS: Patients
      hospitalized for worsening heart failure were classified as having SHF (n=22; LV
      ejection fraction (EF) 34+/-2%) or DHF (n=22; LVEF 62+/-2%). No patient had
      coronary artery disease or biopsy evidence of infiltrative or inflammatory
      myocardial disease. More DHF patients had a history of arterial hypertension and
      were obese. Biopsy samples were analyzed with histomorphometry and electron
      microscopy. Single cardiomyocytes were isolated from the samples, stretched to a
      sarcomere length of 2.2 microm to measure passive force (Fpassive), and activated
      with calcium-containing solutions to measure total force. Cardiomyocyte diameter
      was higher in DHF (20.3+/-0.6 versus 15.1+/-0.4 microm, P<0.001), but collagen
      volume fraction was equally elevated. Myofibrillar density was lower in SHF (36+/
      2% versus 46+/-2%, P<0.001). Cardiomyocytes of DHF patients had higher Fpassive
      (7.1+/-0.6 versus 5.3+/-0.3 kN/m2; P<0.01), but their total force was comparable.
      After administration of protein kinase A to the cardiomyocytes, the drop in
      Fpassive was larger (P<0.01) in DHF than in SHF. CONCLUSIONS: LV myocardial
      structure and function differ in SHF and DHF because of distinct cardiomyocyte
      abnormalities. These findings support the clinical separation of heart failure
      patients into SHF and DHF phenotypes.

PMID- 16618818
TI  - Induction of profound hypothermia for emergency preservation and resuscitation
      allows intact survival after cardiac arrest resulting from prolonged lethal
      hemorrhage and trauma in dogs.
AB  - BACKGROUND: Induction of profound hypothermia for emergency preservation and
      resuscitation (EPR) of trauma victims who experience exsanguination cardiac
      arrest may allow survival from otherwise-lethal injuries. Previously, we achieved
      intact survival of dogs from 2 hours of EPR after rapid hemorrhage. We tested the
      hypothesis that EPR would achieve good outcome if prolonged hemorrhage preceded
      cardiac arrest. METHODS AND RESULTS: Two minutes after cardiac arrest from
      prolonged hemorrhage and splenic transection, dogs were randomized into 3 groups
      (n=7 each): (1) the cardiopulmonary resuscitation (CPR) group, resuscitated with
      conventional CPR, and the (2) EPR-I and (3) EPR-II groups, both of which received
      20 L of a 2 degrees C saline aortic flush to achieve a brain temperature of 10
      degrees C to 15 degrees C. CPR or EPR lasted 60 minutes and was followed in all
      groups by a 2-hour resuscitation by cardiopulmonary bypass. Splenectomy was then
      performed. The CPR dogs were maintained at 38.0 degrees C. In the EPR groups,
      mild hypothermia (34 degrees C) was maintained for either 12 (EPR-I) or 36 (EPR
      II) hours. Function and brain histology were evaluated 60 hours after rewarming
      in all dogs. Cardiac arrest occurred after 124+/-16 minutes of hemorrhage. In the
      CPR group, spontaneous circulation could not be restored without cardiopulmonary
      bypass; none survived. Twelve of 14 EPR dogs survived. Compared with the EPR-I
      group, the EPR-II group had better overall performance, final neurological
      deficit scores, and histological damage scores. CONCLUSIONS: EPR is superior to
      conventional CPR in facilitating normal recovery after cardiac arrest from trauma
      and prolonged hemorrhage. Prolonged mild hypothermia after EPR was critical for
      achieving intact neurological outcomes.

PMID- 16618819
TI  - Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene for
      intracranial aneurysm: a preliminary study.
AB  - BACKGROUND: Our previous studies have shown a significant linkage of intracranial
      aneurysms (IAs) to chromosome 17. METHODS AND RESULTS: Nine genes (TNFRSF13B, M
      RIP, COPS3, RAI1, SREBF1, GRAP, MAPK7, MFAP4, and AKAP10) were selected from 108
      genes that are located between D17S1857 and D17S1871 by excluding 99 genes that
      were pseudogenes, hypothetical genes, or well-characterized genes but not likely
      associated with IA. Direct sequencing of all coding and regulatory regions in 58
      cases (29 pedigree probands and 29 unrelated nonpedigree cases) was performed.
      Deleterious changes were found only in TNFRSF13B, K154X, and c.585 to 586insA in
      exon4. The association of IA with TNFRSF13B was further studied in 304 unrelated
      cases and 332 control subjects. Rare nonsynonymous changes, a splicing acceptor
      site change and a frame shift, were found in unrelated cases (2.3%; 14 of 608)
      more frequently than in control subjects (0.8%; 5 of 664; P=0.035). The
      association study using single-nucleotide polymorphisms in an unrelated case
      control cohort revealed a protective haplotype (odds ratio 0.69, 95% confidence
      interval 0.52 to 0.92, P=0.012) compared with the major haplotype after
      adjustment for covariates. CONCLUSIONS: We propose that TNFRSF13B is one of the
      susceptibility genes for IA.

PMID- 16618820
TI  - Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal
      women.
AB  - BACKGROUND: Epidemiological studies aimed at correlating coronary heart disease
      (CHD) with serum ferritin levels have thus far yielded inconsistent results. We
      hypothesized that a labile iron component associated with non-transferrin-bound
      iron (NTBI) that appears in individuals with overt or cryptic iron overload might
      be more suitable for establishing correlations with CHD. METHODS AND RESULTS: We
      investigated the relation of NTBI, serum iron, transferrin saturation, and serum
      ferritin with risk of CHD and acute myocardial infarction (AMI). The cohort used
      comprised a population-based sample of 11 471 postmenopausal women aged 49 to 70
      years at enrollment in 1993 to 1997. During a median follow-up of 4.3 years
      (quartile limits Q1 to Q3: 3.3 to 5.4), 185 CHD events were identified, including
      66 AMI events. We conducted a case-cohort study using all CHD cases and a random
      sample from the baseline cohort (n=1134). A weighted Cox proportional hazards
      model was used to estimate hazard ratios for tertiles of iron variables in
      relation to CHD and AMI. Adjusted hazard ratios of women in the highest NTBI
      tertile (range 0.38 to 3.51) compared with the lowest (range -2.06 to -0.32) were
      0.84 (95% confidence interval 0.61 to 1.16) for CHD and 0.47 (95% confidence
      interval 0.31 to 0.71) for AMI. The results were similar for serum iron,
      transferrin saturation, and serum ferritin. CONCLUSIONS: Our results show no
      excess risk of CHD or AMI within the highest NTBI tertile compared with the
      lowest but rather seem to demonstrate a decreased risk. Additional studies are
      warranted to confirm our findings.

PMID- 16618821
TI  - Prevalence and determinants of troponin T elevation in the general population.
AB  - BACKGROUND: The prevalence and determinants of cardiac troponin T (cTnT)
      elevation in the general population are unknown, and the significance of
      minimally increased cTnT remains controversial. Our objective was to determine
      the prevalence and determinants of cTnT elevation in a large, representative
      sample of the general population. METHODS AND RESULTS: cTnT was measured from
      stored plasma samples in 3557 subjects of the Dallas Heart Study, a population
      based sample. cTnT elevation (> or =0.01 microg/L) was correlated with clinical
      variables and cardiac MRI findings. The sample weight-adjusted prevalence of cTnT
      elevation in the general population was 0.7%. In univariable analyses, cTnT
      elevation was associated with older age, black race, male sex, coronary artery
      calcium by electron beam CT, a composite marker of congestive heart failure
      (CHF), left ventricular hypertrophy (LVH), diabetes mellitus (DM), and chronic
      kidney disease (CKD) (P<0.001 for each). Subjects with minimally increased (0.01
      to 0.029 microg/L) and increased (> or =0.03 microg/L) cTnT had a similar
      prevalence of these characteristics. In multivariable logistic regression
      analysis, LVH, CHF, DM, and CKD were independently associated with cTnT
      elevation. CONCLUSIONS: In the general population, cTnT elevation is rare in
      subjects without CHF, LVH, CKD, or DM, suggesting that the upper limit of normal
      for the immunoassay should be <0.01 microg/L. Even minimally increased cTnT may
      represent subclinical cardiac injury and have important clinical implications, a
      hypothesis that should be tested in longitudinal outcome studies.

PMID- 16618822
TI  - Anticoagulants and transaminase elevation.

PMID- 16618823
TI  - Images in cardiovascular medicine. Unclassified type of aortopulmonary window.

PMID- 16618824
TI  - Images in cardiovascular medicine. Dynamic myocardial ischemia caused by
      circumflex artery stenosis detected by a new implantable left atrial pressure
      monitoring device.

PMID- 16618825
TI  - Images in cardiovascular medicine. From bad to worse: complete heart block
      leading to ventricular fibrillation.

PMID- 16618826
TI  - Letter regarding article by Burke et al, "role of SCN5A Y1102 polymorphism in
      sudden cardiac death in blacks".

PMID- 16618827
TI  - Letter regarding article by Rademaker et al, "integrated hemodynamic, hormonal,
      and renal actions of urocortin 2 in normal and paced sheep: beneficial effects in
      heart failure".

PMID- 16618828
TI  - Viewpoint: cardiac ultrasound. Interview by Monika Polak, PhD.

PMID- 16618829
TI  - Beta2-adrenergic receptor polymorphisms and sudden cardiac death: a signal to
      follow.

PMID- 16618830
TI  - Myocardial salvage: retrospection, resolution, and radio waves.

PMID- 16618831
TI  - Beta2-adrenergic receptor genetic variants and risk of sudden cardiac death.
AB  - BACKGROUND: Sympathetic activation influences the risk of ventricular arrhythmias
      and sudden cardiac death (SCD), mediated in part by the beta2-adrenergic receptor
      (B2AR). We investigated whether variation in the B2AR gene is associated with SCD
      risk. METHODS AND RESULTS: In this study, 4441 white and 808 black Cardiovascular
      Health Study (CHS) participants were followed up prospectively for SCD and
      genotyped for B2AR Gly16Arg and Gln27Glu polymorphisms. The study was replicated
      in 155 case and 144 control white subjects in a population-based case-control
      study of SCD, the Cardiac Arrest Blood Study (CABS). In CHS, Gly16 and Gln27
      allele frequencies were 62.4% and 57.1% among white and 50.1% and 81.4% among
      black participants. Over a median follow-up of 11.1 years, 156 and 39 SCD events
      occurred in white and black participants, respectively. The Gln27Glu variant was
      associated with SCD risk (P=0.008 for general model). SCD risk was higher in
      Gln27 homozygous participants than in Glu27 carriers (ethnicity-adjusted hazard
      ratio [HR], 1.56; 95% confidence interval [CI], 1.17 to 2.09; P=0.003). The
      increased risk did not differ significantly between white (HR, 1.62; 95% CI, 1.18
      to 2.23) and black (HR, 1.23; 95% CI, 0.61 to 2.48) participants, although the
      confidence interval was wide in blacks. In the CABS replication study, Gln27
      homozygous participants similarly had higher SCD risk than Glu27 carriers (odds
      ratio, 1.64; 95% CI, 1.02 to 2.63; P=0.040). Gly16Arg was not associated with SCD
      risk in either study. CONCLUSIONS: Gln27 homozygous individuals have an increased
      risk of SCD in 2 study populations. Our findings suggest that B2AR plays a role
      in SCD in humans. Study of genetic variation within the B2AR gene may help
      identify those at increased SCD risk.

PMID- 16618832
TI  - Remodeling of early-phase repolarization: a mechanism of abnormal impulse
      conduction in heart failure.
AB  - BACKGROUND: The early phase of action potential (AP) repolarization is critical
      to impulse conduction in the heart because it provides current for charging
      electrically coupled cells. In the present study we tested the impact of heart
      failure-associated electrical remodeling on AP propagation. METHODS AND RESULTS:
      Subepicardial, midmyocardial, and subendocardial myocytes were enzymatically
      dissociated from control and pressure-overload failing left ventricle (LV), and
      APs were recorded. A unique coupling-clamp technique was used to electrically
      couple 2 isolated myocytes with a controlled value of coupling conductance (Gc).
      In sham-operated mice, AP duration manifested a clear transmural gradient, with
      faster repolarization in subepicardial myocytes than in subendocardial myocytes.
      AP propagation from subendocardial to subepicardial myocytes required less Gc
      compared with conduction in the opposite direction. In failing heart, AP
      morphology was dramatically altered, with a significantly elevated plateau
      potential and prolonged AP duration. Spatially nonuniform alteration of AP
      duration in failing heart blunted the transmural gradient of repolarization.
      Furthermore, increased pacing rate prolonged AP duration exclusively in myocytes
      from failing heart, and the critical conductance required for successful AP
      propagation decreased significantly at high frequencies. Finally, in failing
      heart, asymmetry of transmural electrical propagation was abolished. CONCLUSIONS:
      In failing heart, preferential conduction from subendocardial to subepicardial
      myocytes is lost, and failing myocytes manifest facilitated AP propagation at
      fast rates. Together, these electrical remodeling responses may promote
      conduction of premature impulses and heighten the risk of malignant arrhythmia, a
      prominent feature of heart failure.

PMID- 16618833
TI  - Reciprocal relationships between insulin resistance and endothelial dysfunction:
      molecular and pathophysiological mechanisms.
AB  - Endothelial dysfunction contributes to cardiovascular diseases, including
      hypertension, atherosclerosis, and coronary artery disease, which are also
      characterized by insulin resistance. Insulin resistance is a hallmark of
      metabolic disorders, including type 2 diabetes mellitus and obesity, which are
      also characterized by endothelial dysfunction. Metabolic actions of insulin to
      promote glucose disposal are augmented by vascular actions of insulin in
      endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed,
      NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of
      the increase in glucose uptake in response to insulin stimulation.
      Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways in endothelium
      related to production of NO share striking similarities with metabolic pathways
      in skeletal muscle that promote glucose uptake. Other distinct nonmetabolic
      branches of insulin-signaling pathways regulate secretion of the vasoconstrictor
      endothelin-1 in endothelium. Metabolic insulin resistance is characterized by
      pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling,
      which in endothelium may cause imbalance between production of NO and secretion
      of endothelin-1, leading to decreased blood flow, which worsens insulin
      resistance. Therapeutic interventions in animal models and human studies have
      demonstrated that improving endothelial function ameliorates insulin resistance,
      whereas improving insulin sensitivity ameliorates endothelial dysfunction. Taken
      together, cellular, physiological, clinical, and epidemiological studies strongly
      support a reciprocal relationship between endothelial dysfunction and insulin
      resistance that helps to link cardiovascular and metabolic diseases. In the
      present review, we discuss pathophysiological mechanisms, including inflammatory
      processes, that couple endothelial dysfunction with insulin resistance and
      emphasize important therapeutic implications.

PMID- 16618834
TI  - Effect of low-density lipoprotein cholesterol on angiotensin II sensitivity: a
      randomized trial with fluvastatin.
AB  - Increased angiotensin II (Ang II) sensitivity predisposes to hypertension and
      plaque instability. Raised low-density lipoprotein cholesterol (LDL-c) may
      increase Ang II sensitivity, but evidence in humans for this effect of LDL-c is
      limited. In 28, healthy, nonsmoking subjects, aged 30+/-8 years, with familial
      hypercholesterolemia, we determined the difference in infusion rate of Ang II and
      norepinephrine required to increase systolic blood pressure by 20 mm Hg (Pd-20)
      after 4 weeks of placebo and fluvastatin 80 mg daily in a randomized, double
      blind, placebo-controlled, crossover study. Before infusions were started,
      fasting blood samples were taken to measure lipids. After 4 weeks of placebo, the
      mean LDL-c concentration was 6.3+/-1.4 mmol/L. The average decrease of LDL-c was
      1.7+/-0.7 mmol/L after 4 weeks of fluvastatin (P<0.001). The mean Pd-20 for Ang
      II increased by 1.28 ng/kg per minute (95% CI, 2.05 to 0.50; P=0.002) on
      fluvastatin, corresponding with a 26% decrease in Ang II sensitivity. Ang II
      sensitivity, however, remained increased compared with normocholesterolemic
      controls. The Pd-20 values for norepinephrine were unaffected by fluvastatin. The
      present study in healthy, young subjects with isolated hypercholesterolemia shows
      an increased sensitivity to Ang II that partly can be restored by LDL-c-lowering
      therapy. These findings indicate that LDL-c levels directly influence Ang II
      sensitivity.

PMID- 16618835
TI  - Surgical menopause increases salt sensitivity of blood pressure.
AB  - Salt sensitivity of blood pressure is associated with an elevated risk of
      developing hypertension (HTN) and is an independent risk factor for
      cardiovascular disease. The prevalence of HTN increases after menopause. The aim
      of this study was to investigate prospectively whether the loss of ovarian
      hormones increases the occurrence of salt sensitivity among healthy premenopausal
      women. We enrolled 40 normotensive, nondiabetic women (age 47.2+/-3.5),
      undergoing hysterectomy-oophorectomy for nonneoplastic processes and not on
      hormone replacement, to determine the effect of changes in sodium intake on blood
      pressure the day before and subsequently 4 months after surgical menopause. Salt
      loading was achieved using a 2-L normal saline infusion and salt depletion
      produced by 40 mg of intravenous furosemide. A decrease >10 mm Hg in systolic
      blood pressure between salt loading and salt depletion was used to define salt
      sensitivity. Before and after menopause, salt-sensitive women exhibited higher
      waist/hip and waist/thigh ratios (P<0.01). Although all of the women remained
      normotensive, the prevalence of salt sensitivity was significantly higher after
      surgical menopause (21 women; 52.5%) than before (9 women; 22.5%; P=0.01),
      because 12 (38.7%) salt-resistant women developed salt sensitivity after
      menopause. In summary, we demonstrated that the prevalence of salt sensitivity
      doubled as early as 4 months after surgical menopause, without an associated
      increase in blood pressure. Epidemiological studies indicate that development of
      HTN may not occur until 5 to 10 years after menopause. The loss of ovarian
      hormones may unmask a population of women prone to salt sensitivity who, with
      aging, would be at higher risk for the subsequent development of HTN and
      cardiovascular disease.

PMID- 16618836
TI  - Estrogens, salt, blood pressure, and cardiovascular disease in women: how do we
      interpret the data?

PMID- 16618837
TI  - Transposition of great arteries is associated with increased carotid artery
      stiffness.
AB  - Transposition of great arteries is the consequence of abnormal aorticopulmonary
      septation. Animal embryonic data indicate that septation and elastogenesis are
      related events, but human and clinical data are not available. We tested the
      hypothesis that large artery elastic function was impaired in patients with
      transposition of great arteries. We studied 34 patients aged 9 to 19 years, 12+/
      3 years after atrial switch operation; 14 patients aged 7 to 9 years, 8+/-1 years
      after arterial switch operation; and 108 healthy control subjects matched for
      age. Carotid artery diastolic diameter and pulsatile distension were determined
      by echo wall-tracking; carotid blood pressure was measured by tonometry. Systolic
      pressure was higher and diastolic pressure was lower in patients than in
      controls. Patients with atrial and arterial switch repair were compared with
      their respective controls by 2-factor ANOVA. For patients with atrial switch
      repair versus control, stiffness index beta was 4.9+/-1.5 versus 3.1+/-1.0
      (P<0.001); for patients witch arterial switch versus control, stiffness index
      beta was 3.8+/-1.1 versus 2.1+/-0.6 (P<0.001). Similar differences were observed
      for carotid compliance, distensibility, and incremental elastic modulus as well.
      The interaction term was not significant for any of the elastic variables,
      indicating that carotid stiffening was a characteristic of the condition and not
      the consequence of different hemodynamics. Carotid artery is markedly stiffer in
      patients, suggesting that impaired elastogenesis may constitute part of the
      congenital abnormality. Since carotid artery stiffness has been established as an
      independent cardiovascular risk factor, this condition may have consequences in
      the clinical management of these patients.

PMID- 16618838
TI  - Expression of constitutively active angiotensin receptors in the rostral
      ventrolateral medulla increases blood pressure.
AB  - Angiotensin type 1A (AT(1A)) receptors are expressed within the rostral
      ventrolateral medulla, and microinjections of angiotensin II into this region
      increase sympathetic vasomotor tone. To determine the effect of sustained
      increases in AT(1A) receptor density or activity in rostral ventrolateral
      medulla, we used radiotelemetry to monitor blood pressure in conscious rats
      before and after bilateral microinjection into the rostral ventrolateral medulla
      of adenoviruses encoding the wild-type AT(1A) receptor or a constitutively active
      version of the receptor (Asn111Gly, [N111G]AT(1A)). The constitutively active
      receptor signals in the absence of angiotensin II. Adenovirus-directed receptor
      expression was extensively characterized both in vitro and in vivo. We
      established that adenoviral infection was limited to the rostral ventrolateral
      medulla and that receptor expression was sustained for > or =10 days; we also
      observed that adenoviral transgene expression occurs in glia, with no transgene
      expression observed in neurons of the rostral ventrolateral medulla. Rats
      receiving the wild-type AT(1A) receptor showed no change in blood pressure,
      whereas animals receiving the [N111G]AT(1A) receptor displayed an increase in
      blood pressure that persisted for 3 to 4 days before returning to basal levels.
      These data indicate that increased AT(1A) receptor activity (not just
      overexpression) is a primary determinant of efferent drive from rostral
      ventrolateral medulla and reveal counterregulatory processes that moderate AT(1A)
      receptor actions at this crucial relay point. More importantly, they imply that
      constitutive receptor signaling in glia of the rostral ventrolateral medulla can
      modulate the activity of adjacent neurons to change blood pressure.

PMID- 16618839
TI  - Angiotensin type 1A receptors on glial cells in rostral ventrolateral medulla and
      hypertension.

PMID- 16618840
TI  - Angiotensin II type 2 receptor agonist directly inhibits proximal tubule sodium
      pump activity in obese but not in lean Zucker rats.
AB  - We have reported recently that the renal angiotensin II type 2 (AT2) receptors
      are upregulated and involved in promoting natriuresis/diuresis in obese but not
      in lean Zucker rats. In the present study, we tested the hypothesis that there is
      an enhanced AT2 receptor signaling via NO/cGMP pathway leading to greater
      inhibition of the Na(+), K(+)-ATPase (NKA) activity in the proximal tubules (PT)
      of obese rather than lean Zucker rats. The AT2 agonist CGP42112 (0.1 to 100
      nmol/L) inhibited (33% at 100 nmol/L) the NKA activity in the PTs of obese but
      not in lean Zucker rats. The AT2 antagonist PD123319 (1 micromol/L), not the
      angiotensin II type 1 antagonist losartan (1 micromol/L), significantly
      diminished the CGP42112-induced inhibition of the NKA activity in obese rats. The
      AT2 agonist (10 nmol/L)-induced NKA inhibition was abolished by the soluble
      guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (10
      micromol/L), the NO synthase inhibitor NG-nitro-L-arginine methyl ester (100
      micromol/L), and the protein kinase G inhibitor K1388 (2 micromole/L). CGP42112
      (10 nmol/L) caused an increase in serine phosphorylation of NKA alpha1-subunit in
      PT of obese rats. Measurement of cGMP and NO revealed that CGP42112 (0.1 to 100
      nmol/L) increased cGMP and NO accumulation in the PTs of obese but not lean rats.
      The CGP42112-induced stimulation of NO and cGMP was blocked by PD123319 (1
      micromol/L), NG-nitro-L-arginine methyl ester (100 micromol/L), and 1H-[1,2,4]
      oxadiazolo-[4,3-a] quinoxalin-1-one (10 micromol/L) but not by losartan (1
      micromol/L). The data suggest that the AT2 receptor activation via stimulation of
      the NO/cGMP/protein kinase G pathway directly inhibits the tubular NKA activity
      that provides as a mechanism responsible for the AT2 receptor-mediated
      natriuresis in obese but not in lean Zucker rats.

PMID- 16618841
TI  - Angiotensin II decreases the renal MRI blood oxygenation level-dependent signal.
AB  - Acute experimental reduction of renal blood flow decreases the renal blood
      oxygenation level-dependent (BOLD) MRI signal in animals. Angiotensin II also
      reduces renal blood flow, but the ability of BOLD MRI to dynamically detect this
      response has not yet been investigated in humans. Six healthy male volunteers
      underwent an individual dose-finding study to identify the intravenous doses of
      angiotensin II, norepinephrine, and sodium nitroprusside necessary to induce a 15
      mm Hg peak mean arterial blood pressure change. MRI studies followed within 3
      weeks, when angiotensin II (8.8+/-1.4 ng/kg), norepinephrine (52+/-12 ng/kg), and
      sodium nitroprusside (2.0+/-0.3 microg/kg) were given twice in an unblocked,
      randomized sequence while imaging experiments were performed on a 1.5-T Siemens
      Sonata. A multiecho echo-planar imaging sequence was used to acquire T2* maps
      with a temporal resolution of 1 respiratory cycle. Averaged over a renal cortex
      dominated region of interest, angiotensin II caused a shortening of T2* between
      6% and 10%. Sodium nitroprusside and norepinephrine, although of equal potency
      concerning blood pressure responses, did not alter the renal BOLD signal. The
      renal BOLD response to angiotensin II appeared with short onset latency (as early
      as 10 seconds after peripheral intravenous angiotensin II bolus administration)
      suggesting that this response is a consequence of altered perfusion rather than
      increased renal oxygen consumption. The methods described here are suitable to
      assess renal responsiveness to angiotensin II and may, thus, be of great value in
      human hypertension research.

PMID- 16618842
TI  - Calcification and cardiovascular health: new insights into an old phenomenon.

PMID- 16618843
TI  - Sliding window adaptive histogram equalization of intraoral radiographs: effect
      on image quality.
AB  - OBJECTIVES: To investigate whether contrast enhancement by non-interactive,
      sliding window adaptive histogram equalization (SWAHE) can enhance the image
      quality of intraoral radiographs in the dental clinic. METHODS: Three dentists
      read 22 periapical and 12 bitewing storage phosphor (SP) radiographs. For the
      periapical readings they graded the quality of the examination with regard to
      visually locating the root apex. For the bitewing readings they registered all
      occurrences of approximal caries on a confidence scale. Each reading was first
      done on an unprocessed radiograph ("single-view"), and then re-done with the
      image processed with SWAHE displayed beside the unprocessed version ("twin
      view"). The processing parameters for SWAHE were the same for all the images.
      RESULTS: For the periapical examinations, twin-view was judged to raise the image
      quality for 52% of those cases where the single-view quality was below the
      maximum. For the bitewing radiographs, there was a change of caries
      classification (both positive and negative) with twin-view in 19% of the cases,
      but with only a 3% net increase in the total number of caries registrations. For
      both examinations interobserver variance was unaffected. CONCLUSIONS: Non
      interactive SWAHE applied to dental SP radiographs produces a supplemental
      contrast enhanced image which in twin-view reading improves the image quality of
      periapical examinations. SWAHE also affects caries diagnosis of bitewing images,
      and further study using a gold standard is warranted.

PMID- 16618844
TI  - Accuracy of zoomed digital image in the detection of periodontal bone defect: in
      vitro study.
AB  - OBJECTIVES: (1) To evaluate the intraobserver agreement related to image
      interpretation and (2) to compare the accuracy of 100%, 200% and 400% zoomed
      digital images in the detection of simulated periodontal bone defects. METHODS:
      Periodontal bone defects were created in 60 pig hemi-mandibles with slow-speed
      burs 0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm and 3.0 mm in diameter. 180 standardized
      digital radiographs were made using Schick sensor and evaluated at 100%, 200% and
      400% zooming. The intraobserver agreement was estimated by Kappa statistic
      (kappa). For the evaluation of diagnostic accuracy receiver operating
      characteristic (ROC) analysis was performed followed by chi-square test to
      compare the areas under ROC curves according to each level of zooming. RESULTS:
      For 100%, 200% and 400% zooming the intraobserver agreement was moderate
      (kappa=0.48, kappa=0.54 and kappa=0.43, respectively) and there were similar
      performances in the discrimination capacity, with ROC areas of 0.8611 (95% CI:
      0.7660-0.9562), 0.8600 (95% CI: 0.7659-0.9540), and 0.8368 (95% CI: 0.7346
      0.9390), respectively, with no statistical significant differences (chi2-test;
      P=0.8440). CONCLUSIONS: A moderate intraobserver agreement was observed in the
      classification of periodontal bone defects and the 100%, 200% and 400% zoomed
      digital images presented similar performances in the detection of periodontal
      bone defects.

PMID- 16618845
TI  - What happens if you delay scanning Digora phosphor storage plates (PSPs) for up
      to 4 hours?
AB  - OBJECTIVES: To assess, both objectively and subjectively, the effects of
      different combinations of storage conditions and delaying scanning for up to 4 h
      on digital images captured using Digora phosphor storage plates (PSPs). METHOD:
      Standardized images were obtained of an aluminium step wedge and dry mandible in
      acrylic using GE 1000 and phosphor storage plates (PSPs) from the Digora
      (Soredex) digital system. 12 plates were exposed and immediately scanned to
      produce the baseline gold standard. The plates were re-exposed and stored using
      three different storage combinations--(A) ambient temperature, (R) refrigeration
      and (S) low humidity, and then scanned after 10 min, 30 min, 1 h, 2 h, 3 h or 4
      h. The objective analysis was carried out by pixel density measurements and the
      data analysed statistically using analysis of variance. Subjective analysis was
      carried out by three oral radiologists and the results analysed using the Mann
      Whitney U-test. RESULTS: Objective analysis showed loss of pixel density after 4
      h using all storage combinations. Subjectively, this loss of density was not
      evident. CONCLUSION: There is a loss of image density at 4 h when using Digora
      PSPs which can not be detected clinically, but could compromise multisite
      research.

PMID- 16618846
TI  - End-user survey for digital sensor characteristics: a pilot questionnaire study.
AB  - OBJECTIVE: To survey end-user opinions on dental digital sensor characteristics
      for the design of a new X-ray imaging sensor. MATERIALS AND METHODS: 100
      questionnaires were sent out to dentists and dental radiologists. The
      questionnaire consisted of six parts related to dental sensors. A: Details about
      the respondent; B: Prioritization of most important aspects of digital sensors;
      C: Rating advantages and D: disadvantages of digital sensors; F: Dental features
      that need to be enhanced by digital sensors; G: End-user comments. RESULTS: Fifty
      six questionnaires were returned. Contrast resolution and imaging time were
      assessed as the most and the least important aspects, respectively. Aspects
      considered as advantages by approximately 80% of respondents were: optimal
      contrast resolution, increased specificity, increased discrimination between
      diseased and healthy tissue, increased sensitivity, lower dose to the patient by
      more than 20%; as a disadvantage, increased patient dose was given. Dental
      features considered important by over 80% of the respondents were for intraoral
      radiographs: the visibility of caries, periapical, periodontal, and bone lesions;
      for panoramic radiographs: reduction of ghost images, image sharpness and bone.
      Bone and soft tissues on cephalograms and bone on temporomandibular joint (TMJ)
      tomograms were mentioned by over 70%. CONCLUSION: The most desired characteristic
      for a new sensor is contrast resolution. Dose saving is not considered as
      important unless it is more than 20%. Examination time is not a major issue.
      Caries, periapical and periodontal, and bone lesions for intraoral radiographs,
      reduction of ghost images, image sharpness and bone for panoramic radiographs
      were the most frequently mentioned dental features that should be enhanced by
      digital sensors.

PMID- 16618847
TI  - Osseous abnormalities of the mandibular condyle: diagnostic reliability of cone
      beam computed tomography compared with helical computed tomography based on an
      autopsy material.
AB  - OBJECTIVES: We compared the diagnostic reliability of cone beam computed
      tomography (3DX) and helical computed tomography (helical CT) for the detection
      of osseous abnormalities of the mandibular condyle, using macroscopic
      observations as the gold standard. METHODS: Twenty-one temporomandibular joint
      autopsy specimens underwent imaging with 3DX and helical CT. The specimens were
      macroscopically evaluated for cortical erosion or osteophytosis and sclerosis.
      The images were independently assessed for the same osseous abnormalities.
      Observations with the two imaging modalities were compared with the macroscopic
      observations using the McNemar test. RESULTS: According to the macroscopic
      observations, 10 of the 21 mandibular condyles and one fossa showed osseous
      abnormalities. 3DX detected abnormalities in eight of these condyles and helical
      CT identified abnormalities in seven, giving a sensitivity of 0.80 for 3DX and
      0.70 for helical CT. The specificity of the condyle assessment was 1.0 for both
      3DX and helical CT and hence, the accuracy was 0.90 and 0.86, respectively. No
      significant differences were detected between the 3DX and helical CT for
      assessment of osseous abnormalities of the mandibular condyle (P=0.286).
      CONCLUSIONS: The cone beam CT equipment 3DX is a dose-effective and a cost
      effective alternative to helical CT for the diagnostic evaluation of osseous
      abnormalities of the mandibular condyle.

PMID- 16618848
TI  - Reconstruction of facial morphology from laser scanned data. Part I: reliability
      of the technique.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of scanning
      parameters on the precision of the data acquired using a facial laser scanner and
      to assess the reliability of automatic model recording in humans. METHODS: Data
      were acquired using a laser scanner (Cyberware 3030RGB); analysis and
      measurements were performed with Rapid Form 2004 software. A mannequin and six
      volunteers were scanned to investigate the effects of environmental conditions,
      positioning, head orientation, and software procedures. Precision and accuracy of
      the data were evaluated comparing six linear measures calculated on scanned data
      with those obtained directly. Two sessions with different head inclination were
      performed. The reliability of repeated scans was also assessed measuring the
      distance between the surfaces reconstructed from two separate scans of the same
      subject, at 12 anatomical points, in 5 subjects, during two sessions using a
      different head inclination. Differences were analysed using paired t-tests or
      analysis of variance (ANOVA). RESULTS: The accuracy of scanning was +/-0.65 mm.
      The development of a specific protocol resulted in a mean scanning error of 1-1.2
      mm and a recording error of 0.3-0.4 mm on repeated scans of human subjects.
      CONCLUSIONS: This study indicates that scanning of the human face may be hampered
      by errors and artefacts, mainly due to movements. While the effect of trembling
      and involuntary movements during the exam may be minimized using faster scanning
      devices, comparative observation over time may be affected by unreal differences
      due to the uncertainty of facial expression. The overall error is, however, in
      the range useful for most clinical studies.

PMID- 16618849
TI  - Conventional and indirect digital radiographic interpretation of oral unilocular
      radiolucent lesions.
AB  - OBJECTIVES: To compare the diagnostic processes for the main unilocular
      radiolucent lesions of the mandible in the presence of the following variables:
      conventional and digital radiography, specialization of the examiner and type of
      lesion. METHODS: Twenty-four panoramic radiographs were selected from the
      archives of the AC Camargo Hospital (Sao Paulo, Brazil), aiming at comparing the
      diagnostic processes for similar unilocular radiolucent lesions of the mandible,
      with the following histopathological diagnosis: six ameloblastomas, six
      dentigerous cysts, six keratocysts and six traumatic bone cysts. The radiographs
      were scanned and processed using the Trophy 2000 software. Three specialists,
      each from four related areas (pathologists, stomatologists, radiologists and oral
      surgeons), randomly evaluated the radiographs before and after digitalization.
      RESULTS: The kappa statistic showed a high level of agreement between results
      obtained using the two radiographic techniques. This means that, in general, the
      examiners diagnosed the same cases correctly or incorrectly regardless of the
      method used. CONCLUSIONS: Based on generalized estimating equations, it was
      concluded that the probability of correct diagnosis does not depend on the kind
      of lesion, on the radiographic technique or on the specialization of the
      examiner. In view of the differing opinions of the specialists regarding the
      diagnostic validity of some software features available and of the results
      obtained in indirect digital technique, it may be reasonable to reconsider its
      use for diagnosis of bone pathology.

PMID- 16618850
TI  - Comparing the accuracy of panoramic and intraoral radiography in the diagnosis of
      proximal caries.
AB  - OBJECTIVES: The purpose of this study was to compare the diagnostic accuracy of
      panoramic and intraoral radiographic surveys in the diagnosis of proximal caries
      according to the different dental regions (maxillary and mandibular incisor,
      canine, premolar and molar). METHODS: In this study, full mouth series and
      panoramic radiographs of 79 patients were used. The radiographs were evaluated
      for proximal caries by three observers. The diagnostic accuracy of radiographic
      surveys for each dental region was assessed by means of receiver operating
      characteristic (ROC) curve analysis. RESULTS: Full mouth series was the most
      efficient method in the diagnosis of caries for incisor and canine teeth.
      However, full mouth series and combination of panoramic plus bitewings had
      similar diagnostic accuracy for premolar and molar teeth. CONCLUSIONS: Panoramic
      survey alone was not sufficient for the diagnosis of proximal caries for the
      entire dentition. The combination of panoramic plus bitewing plus anterior
      periapical survey exhibited a diagnostic accuracy for proximal caries that was
      comparable with full mouth series.

PMID- 16618851
TI  - Root canal system in the mesiobuccal root of the maxillary first molar: an in
      vitro comparison study of computed tomography and histology.
AB  - OBJECTIVES: The purpose of this study was to investigate a new diagnostic
      approach to the examination of the canal configuration of the mesiobuccal root of
      the maxillary first molar. MATERIALS AND METHODS: High-resolution computed
      tomography (CT) was compared with histology in vitro. There were 152 teeth
      investigated and classified according to Weine and Vertucci. RESULTS: CT
      describes the exact canal configuration, verifying information identical to
      histology, and thus serving as the "gold standard" in vitro. With regard to canal
      position, 9 (5.92%) of the teeth examined were Vertucci type 1, 48 (31.58%) were
      Vertucci type 2, 91 (59.87%) were Vertucci type 4, 1 (0.66%) was Vertucci type 5,
      1 (0.66%) was Vertucci type 6. Of the 152 teeth examined, 3 (1.97%) could not be
      classified using Weine, 2 (1.31%) could not be classified according to either
      Weine or Vertucci, and no Vertucci types 3, 7 or 8 were identified. CONCLUSIONS:
      CT offers complete information on the number and configuration of root canals. As
      the root canal configuration of the adult does not change rapidly, CT
      investigations can be used for multiple subsequent treatments.

PMID- 16618852
TI  - Osteoporosis and mandibles.
AB  - OBJECTIVES: The purpose of this study was to find out whether mandibular bone
      tissues on dental panoramic tomograms (DPTs) are statistically significantly
      different between osteoporotic and non-osteoporotic women. We wanted to develop a
      simple method of common DPT analysis that could represent a simple, inexpensive
      and readily available screening tool for osteoporosis. METHODS: DPT images of 36
      women with primary osteoporosis were compared with 20 DPT images of non
      osteoporotic women of the same age group. Scanned DPTs were analysed using public
      computer software. Mandibular atrophy was assessed by six anatomic indexes.
      Anatomic indexes were divided into subgroups regarding the presence of teeth.
      Relative bone density (RBD) was assessed using a colour histogram (CH) plugin.
      Nine RBD indexes were calculated as relations of CH values measured on specific
      sites of the mandible. RESULTS: The subtractions of average values of anatomic
      indexes with and without a tooth were 1.5 to 2.5 times higher in the osteoporotic
      group of women. Average of RBD indexes differed statistically significantly
      between the groups (P<0.05). Three RBD indexes differed statistically
      significantly between groups (P<0.05). CONCLUSIONS: Mandibular bone tissues on
      DPTs are statistically significantly different between osteoporotic and non
      osteoporotic women. RBD of the mandible is statistically significantly lower in
      the osteoporotic group of women. We developed a simple method of common DPT
      analysis, which could represent a simple, inexpensive and readily available
      screening tool for osteoporosis.

PMID- 16618853
TI  - Characteristics and prevalence of non-syndrome multiple supernumerary teeth: a
      retrospective study.
AB  - OBJECTIVE: The goal of this study was to evaluate the radiological and clinical
      findings of non-syndromic multiple (five or more) supernumerary teeth in patients
      radiographically examined between 1999 and 2004. METHODS: Among 9550 patients,
      251 cases of supernumerary teeth were found, including six cases of multiple
      supernumerary teeth. Patients with multiple supernumerary teeth were evaluated
      for age, sex, unilateral or bilateral distribution of the teeth, localization,
      morphology and complications or associated pathologies such as dentigerous cysts,
      eruption anomalies, resorption of adjacent teeth, displacement of tooth germ,
      malformation, migration, neurological symptoms, and secondary and periapical
      infections. RESULTS: All patients were male and most of the multiple
      supernumerary teeth were seen in the premolar region. The prevalence of multiple
      supernumerary teeth was 0.06%. Out of 37 multiple supernumerary teeth examined,
      30 were impacted. Various associated anomalies were seen in 21.6% of cases.
      Although the mean age was high (23.1 years), no pathologies such as root
      resorption on adjacent teeth or cystic formation were observed, in contradiction
      of previous studies. CONCLUSION: In agreement with previous studies, the majority
      of supernumerary teeth were seen in the lower premolar region. That all patients
      with multiple supernumerary teeth were male and that most of these teeth were
      impacted was also in agreement with previous studies. The order of location
      frequency in previous studies has been premolar-molar-anterior; we found the
      order to be premolar-anterior with no supernumerary molar teeth observed. It was
      also interesting that no serious pathological findings were recorded.

PMID- 16618854
TI  - Clinical significance and variation of the advanced calcified stylohyoid complex
      detected by panoramic radiographs among 80-year-old subjects.
AB  - OBJECTIVES: To evaluate the clinical significance and variation of a calcified
      stylohyoid complex associated with advanced calcification as detected on
      panoramic radiographs among 80-year-old subjects. METHODS: Panoramic radiographs
      of 659 patients (262 men and 397 women) and data of their general and dental
      health conditions were used for the evaluation of the relationship between a
      calcified stylohyoid complex and general health among 80-year-olds. This study
      was part of the 8020 Data Bank Survey, which was designed to collect the baseline
      data of general and dental health conditions in 80-year-old subjects. The
      morphology of the calcified stylohyoid complexes was allocated to one of 12
      patterns. The lengths of the calcified stylohyoid complex were measured directly
      on the radiographs from the caudal margin of the tympanic plate to the tip of the
      styloid process. RESULTS: All of the stylohyoid complexes from the 659 panoramic
      radiographs could be allocated to one of 12 morphological patterns, and some of
      their radiographic findings suggested calcification of the carotid artery and
      lymph nodes. In 80-year-old subjects, the average length of the calcified
      stylohyoid complexes was 36.7 mm, and ranged from 0.0 mm to 153.0 mm. There
      appeared to be correlations between the length of the calcified stylohyoid
      complex and serum calcium concentration and heel bone density, but not with the
      Community Periodontal Index (CPI). CONCLUSIONS: Dentists should recognize the
      existence of morphological variation in calcified stylohyoid complexes,
      especially in length, apparent on panoramic radiographs of 80-year-old patients.
      In addition, the longer length of the calcified stylohyoid complexes in 80-year
      old patients may be a predictor of bone density and high serum calcium
      concentration level. The findings from the present study may provide potentially
      life-saving information about elderly people.

PMID- 16618855
TI  - A randomized double blinded study to assess the efficacy of a laser-guided
      collimator on dental radiography training.
AB  - OBJECTIVES: To assess the effect of a laser-guided collimator in intraoral
      radiography training. METHODS: A custom-made collimator with four red laser
      diodes on each corner on the rim of an aluminium alloy cubic housing was
      fabricated. The laser used low power diodes, which are classified as laser-safe
      by the United States Food and Drug Administration (FDA). When activated, the
      effective dimensions of the laser beams were 4 cm x 4.5 cm. Eighteen dental
      hygiene students were randomized into test and control groups. The Laser group
      used a rectangular collimator with the laser device, while the Non-laser group
      used a conventional rectangular collimator. Each group attended nine intraoral
      radiography training sessions. All radiographs were assessed and were classified
      into three categories: Excellent, Acceptable and Repeat, by a masked academic
      staff member. Reasons for repeats were marked. Statistical comparisons between
      the two groups were made. RESULTS: A total of 2334 radiographs were made. Conecut
      was more common on bitewings than periapicals. The Laser group produced fewer
      conecuts than the Non-laser group. The Laser group produced more excellent
      radiographs with fewer repeats than the Non-laser group, but there was not a
      significant difference. CONCLUSIONS: The laser-guided collimator helped the
      students to produce fewer repeats in a shorter period of time. It was an
      effective training aid.

PMID- 16618856
TI  - Vascular malformations of the tongue: MRI findings on three cases.
AB  - Vascular malformations are common lesions accounting for approximately 7% of all
      benign tumours, the majority of which develop in the head and neck region.
      Generally, vascular malformations such as lymphangiomas, haemangiomas, and
      arteriovenous communications in the head and the neck represent only an aesthetic
      problem. However, when localized in the tongue, these lesions can create clinical
      problems consisting, in the majority of cases, in spontaneous haemorrhage from
      the mouth. Although uncommon, progressive asymmetric growth of the tongue
      (macroglossia) can be also observed. Three consecutive cases of vascular
      malformations of the tongue have been studied with magnetic resonance imaging
      (MRI). Neither contrast medium administration nor angio-MR technique was used. In
      our experience, MR appears to be the ideal technique to define the site,
      extension and origin of vascular malformations, due to its ability to depict the
      typical signal flow voids in the lesions and to differentiate slow-flow lesions
      from high-flow ones.

PMID- 16618857
TI  - Polymorphous low grade adenocarcinoma presenting an uncommon radiographic aspect.
AB  - The aim of this study was to present clinical, histological and
      immunohistochemical aspects of a polymorphous low grade adenocarcinoma occurring
      in the mandible. A radiolucent tumour, located in the right mandible, was removed
      from a 40-year-old woman. Radiographic and CT exams revealed that the lesion
      expanded bucco-lingual cortical plates and presented an irregular scalloping of
      the bone. The surrounding lining mucosa was intact. The patient underwent total
      surgical removal of the lesion with an intraoperative biopsy. Histological
      diagnosis was polymorphous low-grade adenocarcinoma confirmed by
      immunohistochemical study. One-year follow up was uneventful. The accurate
      diagnosis of lesions presenting unusual clinical aspects, as the one presented
      here, is critical for correctly handling treatment.

PMID- 16618858
TI  - Chronic sinusitis unresponsive to medical therapy: a case of maxillary sinus
      actinomycosis focusing on computed tomography findings.
AB  - Actinomycosis of the paranasal sinuses is a rare occurrence and its clinical
      presentation does not suggest a specific diagnosis. Therefore, actinomycosis
      should be included in the differential diagnosis of neoplasms and granulomatous
      lesions of the head and neck region. However, the differentiation from a
      malignant neoplasm is not easy because the radiological findings are frequently
      similar and positive cultures are difficult to obtain. This report highlights the
      clinical progress of paranasal actinomycosis associated with some computed
      tomography findings that can be extremely helpful in the correct diagnosis. The
      characteristics of the disease are described and the relevant literature is
      discussed.

PMID- 16618859
TI  - Pseudo multiple and enlarged mandibular canals: the evidence-based response of
      cone beam computed tomography.

PMID- 16618860
TI  - Dapsone as a potential treatment for cutaneous Rosai-Dorfman disease with
      neutrophilic predominance.

PMID- 16618861
TI  - Multiple primary melanoma: two-year results from a population-based study.
AB  - OBJECTIVE: To assess the frequency of occurrence and risk factors for multiple
      primary melanoma. DESIGN: Population-based, case-control study. SETTING: New
      Hampshire. PARTICIPANTS: Three-hundred fifty-four New Hampshire residents with a
      confirmed first diagnosis of cutaneous melanoma. MAIN OUTCOME MEASURE: Diagnosis
      of a subsequent primary cutaneous melanoma. RESULTS: An additional melanoma
      occurred in 27 individuals (8%) within 2 years of their initial diagnosis,
      including 20 (6%) within the first postdiagnosis year. In 9 (33%) of these 27
      cases, at least 1 subsequent melanoma was deeper than the first tumor. The 27
      individuals with a subsequent melanoma diagnosis were classified as "cases" and
      were compared on the basis of risk factors to the 327 "controls" with a single
      melanoma diagnosis. The data indicate an inverse relation of risk of multiple
      primary melanomas with multiple blistering sunburns (P = .01 for the trend); the
      odds ratio (OR) was 0.32 (95% confidence interval [CI], 0.11-0.93) for 2 or more
      sunburns compared with none. The number of atypical moles was significantly
      related to increased risk (P = .004 for the trend). The presence of 3 or more
      atypical moles compared with none was associated with more than a 4-fold risk of
      multiple primary melanomas (OR, 4.29; 95% CI, 1.51-12.16). CONCLUSIONS:
      Additional melanomas occur more frequently than previously shown. Our study
      confirms that atypical moles are strongly associated with risk of multiple
      primary melanomas but provides little evidence that risk is influenced by
      pigmentary characteristics, hours of sun exposure, or benign moles. The inverse
      association with blistering sunburn may reflect the influence of an unmeasured
      covariate.

PMID- 16618862
TI  - Skin cancer examination teaching in US medical education.
AB  - OBJECTIVE: To determine physician preparation for performing the skin cancer
      examination (SCE). DESIGN: We evaluated medical students' observation, training,
      and practice of the SCE; hours spent in a dermatology clinic; and self-reported
      skill level for the SCE by a self-administered survey. PARTICIPANTS: Graduating
      students at 7 US medical schools during the 2002-2003 academic year. MAIN OUTCOME
      MEASURES: Percentages of students reporting SCE skill observation, training, and
      practice. RESULTS: Of 934 students, 659 (70.6%) completed surveys. Twenty-three
      percent of students had never observed an SCE, 26.7% had never been trained to
      perform an SCE, and 43.4% had never examined a patient for skin cancer. Only
      28.2% rated themselves as somewhat or very skilled in the SCE. This rate dropped
      to 19.7% among 553 students who had not completed a dermatology elective.
      Compared with students without training, students who had been trained at least
      once in the SCE were 7 times more likely to rate themselves as being somewhat or
      very skilled in the SCE. Sixty-nine percent of students agreed that insufficient
      emphasis in their medical training was placed on learning about the SCE.
      CONCLUSIONS: This survey documents the need for more consistent training of
      medical students in SCE. Even brief curricular additions would augment students'
      perceived skill levels and improve practice patterns and competencies of future
      physicians. More frequent and improved SCEs might result in earlier detection of
      melanoma and nonmelanoma skin cancers by nondermatologists, with significant
      public health benefits.

PMID- 16618863
TI  - Skills training to learn discrimination of ABCDE criteria by those at risk of
      developing melanoma.
AB  - OBJECTIVE: To develop skin self-examination skills by improving the use of the
      ABCDE criteria by those at risk of developing melanoma. DESIGN: Ten single-sex
      groups of 10 unrelated adults received a knowledge-based intervention followed by
      skills training. SETTING: Classroom in the ambulatory care area of a hospital.
      Patients One hundred unrelated adults with either a personal or family history of
      melanoma and no previous skin self-examination counseling. Interventions A
      dermatologist presented information, and each subject read a brochure and
      reviewed a bookmark. The facilitator led the group discussions about scoring each
      feature and the decision to seek medical care. Measurement of moles with a ruler
      and a pencil eraser and the use of an illuminated magnifying lens were
      demonstrated. Preintervention and postintervention assessments were performed for
      each intervention. MAIN OUTCOME MEASURE: Recognition of A, B, C, D, and E traits.
      RESULTS: The subjects preferred the bookmark (87% of subjects), opaque ruler (94%
      of subjects), and lighted magnifying lens (81% of subjects) to reading the
      brochure, which was felt to take too long. Recognition of border irregularity,
      color variation, and diameter improved significantly after the intervention.
      Women recognized color variation more often than men (94% vs 62%; odds ratio
      [OR], 23.7; 95% confidence interval [CI], 16.1-50.5). Men identified irregular
      borders more often than women (91% vs 75%; OR, 16.8; 95% CI, 4.5-22.6). Women
      appropriately decided to see a physician more often than men (81% vs 57%; OR,
      13.5; 95% CI, 7.1-28.4). CONCLUSIONS: Determining the presence of the A, B, C,
      and E criteria is challenging for the novice. Skills training aided performance
      of skin self-examination. Differences in proclivities according to sex suggest
      that if men and women form partnerships for skin checks, they may learn from each
      other, and their combined strengths will promote detection of early melanomas.

PMID- 16618864
TI  - Differences in biopsy techniques of actinic keratoses by plastic surgeons and
      dermatologists: a histologically controlled pilot study.
AB  - OBJECTIVE: To compare differences in biopsy techniques of actinic keratoses
      between dermatologists and plastic surgeons. DESIGN: Blinded, comparative,
      retrospective study. SETTING: Dermatopathology laboratory at a major academic
      medical center with referral of outside cases. Intervention We reexamined the
      histopathologic slides of 405 actinic keratosis biopsy specimens obtained by
      plastic surgeons and dermatologists from January 1, 1992, through May 31, 2002.
      We were specifically interested in the type of biopsy technique (shave, punch, or
      excisional biopsy) used for the surgical management of actinic keratoses by both
      groups of physicians. We also recorded the clinical diagnoses rendered on the
      dermatopathology request form and compared them with the histopathologic
      diagnoses. RESULTS: Excisional biopsies were performed by plastic surgeons in
      50.0% of the cases, compared with only 1.4% by dermatologists. In contrast, shave
      biopsies of actinic keratoses were performed by plastic surgeons in only 32.4% of
      the cases, compared with 89.4% by dermatologists. Only 1 (0.5%) of the 198
      dermatopathology request forms submitted by the plastic surgeons mentioned
      actinic keratosis, compared with 82 (39.6%) of 207 histopathologic evaluation
      requests submitted by dermatologists. CONCLUSIONS: The predominance of excisional
      biopsies of actinic keratoses by plastic surgeons may be related to a different
      ability in the clinical recognition of actinic keratoses compared with that of
      dermatologists. The surgical approach of dermatologists to shave diagnostically
      uncertain cutaneous lesions is less invasive than that of plastic surgeons and is
      more likely to achieve a better cosmetic outcome.

PMID- 16618865
TI  - UV tanning advertisements in high school newspapers.
AB  - OBJECTIVE: To examine the increasing use of UV tanning parlors by adolescents,
      despite the World Health Organization recommendation that no one under the age of
      18 years use UV tanning devices. DESIGN: We examined tanning advertisements in a
      sample of public high school newspapers published between 2001 and 2005 in 3
      Colorado counties encompassing the Denver metropolitan area. RESULTS: Tanning
      advertisements appeared in newspapers from 11 (48%) of 23 schools. Newspaper
      issues (N = 131) contained 40 advertisements placed by 18 tanning parlors.
      Advertisements commonly offered discounts (19 of 40) including unlimited tanning
      offers (15 of 40). Thirteen advertisements featured non-UV tanning treatments,
      and 2 advertisements mentioned parental consent or accompaniment for UV tanning.
      CONCLUSIONS: UV radiation, a classified carcinogen, is commonly and specifically
      marketed to adolescents through high school newspaper advertising. Public health
      skin cancer prevention policies should include the prohibition of UV tanning
      advertising to minors.

PMID- 16618866
TI  - Indoor tanning attitudes and practices of US dermatologists compared with other
      medical specialists.
AB  - OBJECTIVE: To compare the indoor tanning attitudes and practices of
      dermatologists with physicians in other medical specialties (internal medicine,
      pediatrics, and family medicine) commonly providing sun safety counseling to
      patients. DESIGN: Cross-sectional study. SETTING: Questionnaire mailed to
      randomly selected US dermatologists, internists, family practitioners, and
      pediatricians. RESULTS: The overall response rate was 38% (364/949): 71%
      indicated that patients had asked their opinions about indoor UV tanning, 80%
      believed that UV tanning was unsafe, and 90% agreed they would counsel patients
      against nonmedical indoor UV tanning. Many supported increased UV tanning
      legislation, including minimum age restrictions (91%) and parental consent
      requirements (90%). Dermatologists were significantly more likely than other
      physicians to respond to the survey (52% vs 31%, P<.001), speak with patients
      about indoor UV tanning (odds ratio [OR], 26.5; 95% confidence interval [CI], 9.5
      74.1]), believe that indoor UV tanning is unsafe (OR, 14.0; 95% CI, 5.0-39.4),
      and support increased regulation (OR, 11.7; 95% CI, 1.5-88.5). Women discouraged
      indoor UV tanning more than men (OR, 5.2; 95% CI, 1.8-15.2). Physicians who had
      used indoor UV tanning (19%) more often agreed that non-UV tanning lotion (OR,
      2.0; 95% CI, 1.1-3.8) and airbrush tanning (OR, 1.9; 95% CI, 1.1-3.4) were safe
      but did not differ in attitudes regarding UV tanning safety. Physicians
      practicing in the Northeast and Midwest were more likely to support UV tanning to
      improve mood (OR, 2.0; 95% CI, 1.1-3.5) and more commonly believed that UV
      tanning could help treat depression (OR, 2.6; 95% CI, 1.5-4.6) or prevent vitamin
      D deficiency (OR, 1.7; 95% CI, 1.0-2.8). CONCLUSIONS: Physicians, especially
      dermatologists, are frequently asked about and generally discourage indoor UV
      tanning. Dermatologists regard indoor UV tanning more negatively compared with
      other physicians. Physician sex and geographic location were associated with
      specific indoor UV tanning attitudes.

PMID- 16618867
TI  - Tissue microarray analysis of methylthioadenosine phosphorylase protein
      expression in melanocytic skin tumors.
AB  - BACKGROUND: Using tissue microarrays, we investigated whether methylthioadenosine
      phosphorylase (MTAP) protein expression is associated with clinicopathologic
      variables in benign and malignant melanocytic skin tumors. OBSERVATIONS:
      Cytoplasmic MTAP expression was detected in 227 (72.1%) of 315 informative cases.
      Expression was significantly reduced in primary malignant melanomas and in
      melanoma metastases compared with benign nevi (P<.001 for both). No difference
      was noted in MTAP expression between primary malignant melanomas and melanoma
      metastases. In primary malignant melanomas, a Ki67-labeling index less than 5%
      was associated with MTAP expression (P = .04), suggesting that loss of MTAP
      expression is associated with proliferation. No other variables had significant
      associations with MTAP expression. Lymph node metastases demonstrated
      significantly higher MTAP expression compared with skin metastases (P = .01). In
      the overall cohort, MTAP expression was not associated with prognosis. Among 26
      patients with MTAP-positive melanomas and tumor recurrence, 18 patients who
      received interferon therapy had a significant benefit compared with 8 patients
      who did not receive interferon therapy (P = .009). This was not seen in the
      patients with MTAP-negative tumors. Conclusion Methylthioadenosine phosphorylase
      protein expression may be a predictive marker of interferon therapy resistance in
      patients with melanoma and disease progression.

PMID- 16618868
TI  - Morphologic changes of acquired melanocytic nevi with eccentric foci of
      hyperpigmentation ("Bolognia sign") assessed by dermoscopy.
AB  - BACKGROUND: Melanocytic nevi with eccentric foci of hyperpigmentation ("Bolognia
      sign") can be considered as a melanoma-simulating type of acquired melanocytic
      nevus. We report on the morphologic changes of this type of melanocytic nevus
      over a 39-month period of dermoscopic follow-up. OBSERVATIONS: A 5-year-old girl
      had a 4-mm brown papule with a peripheral blue-black area on her right upper arm.
      The eccentric focus of the hyperpigmentation corresponded dermoscopically to a
      blue-gray area of pigmentation associated with irregular brown-black globules or
      dots and partially with a superficial black network. After 39 months, a globular
      type of acquired melanocytic nevus was detectable, which clinically and
      dermoscopically appeared to be completely benign. A nearly identical situation
      was observed in 5 other melanocytic nevi, underlining the involution of the
      pigmented foci in these nevi. The histopathologic diagnoses of 2 lesions were
      consistent with a compound type of acquired melanocytic nevus with eccentric foci
      of hyperpigmentation. CONCLUSIONS: Dermoscopy allows identification of a
      morphologic pathway of modifications, probably typical for this type of
      melanocytic nevus in children, and therefore enables avoidance of surgical
      excision with attendant hypertrophic scarring in children. Conversely, in adults,
      when dermoscopic follow-up of melanocytic nevi reveals eccentric foci of
      hyperpigmentation, surgical excision of the lesion is indicated.

PMID- 16618869
TI  - Recent tanning bed use: a risk factor for melanoma.
AB  - BACKGROUND: Individuals at increased risk of melanoma should use sun-protective
      measures to decrease their risk of developing melanoma. OBSERVATION: We report a
      case of a 39-year-old patient with a CDKN2A mutation who developed 3 primary
      melanomas within a few years of initiating tanning bed use. CONCLUSION: Intense
      UV exposure as an adult likely contributed to the development of additional
      primary melanomas in this individual.

PMID- 16618870
TI  - Multiple pruritic papules from lone star tick larvae bites.
AB  - BACKGROUND: Ticks are the second most common vectors of human infectious diseases
      in the world. In addition to their role as vectors, ticks and their larvae can
      also produce primary skin manifestations. Infestation by the larvae of ticks is
      not commonly recognized, with only 3 cases reported in the literature. The
      presence of multiple lesions and partially burrowed 6-legged tick larvae can
      present a diagnostic challenge for clinicians. OBSERVATION: We describe a 51-year
      old healthy woman who presented to our clinic with multiple erythematous papules
      and partially burrowed organisms 5 days after exposure to a wooded area in
      southern Kentucky. She was treated with permethrin cream and the lesions resolved
      over the following 3 weeks without sequelae. The organism was later identified as
      the larva of Amblyomma species, the lone star tick. CONCLUSIONS: Multiple
      pruritic papules can pose a diagnostic challenge. The patient described herein
      had an unusually large number of pruritic papules as well as tick larvae present
      on her skin. Recognition of lone star tick larvae as a cause of multiple bites
      may be helpful in similar cases.

PMID- 16618871
TI  - Human infestation by larval Amblyomma ticks.

PMID- 16618873
TI  - Too many moles.

PMID- 16618872
TI  - A call for the development and implementation of a targeted national melanoma
      screening program.

PMID- 16618874
TI  - Functional analysis of genes involved in melanoma.

PMID- 16618875
TI  - Bullae on the wrists of an 11-year-old boy--quiz case.

PMID- 16618877
TI  - A reddish nodule on the glans penis--quiz case.

PMID- 16618876
TI  - An erythematous and pigmented lesion of the abdomen--quiz case.

PMID- 16618878
TI  - Nodule on the penis--quiz case.

PMID- 16618879
TI  - Evaluation of medical students' knowledge, attitudes, and personal practices of
      sun protection and skin self-examination.

PMID- 16618880
TI  - Improving skin cancer prevention and detection education in US medical schools.

PMID- 16618881
TI  - A model to teach elliptical excision and basic suturing techniques.

PMID- 16618882
TI  - In consideration of the E in the melanoma ABCDE mnemonic.

PMID- 16618883
TI  - ABCD, ABCDE, and ABCCCDEEEEFNU.

PMID- 16618884
TI  - Usefulness of dermoscopy to monitor clinical efficacy of imiquimod treatment for
      lentigo maligna.

PMID- 16618885
TI  - Man sees only what he knows.

PMID- 16618886
TI  - Treatment of precancerous and cancerous lesions of chronic arsenicism with 5%
      imiquimod cream.

PMID- 16618887
TI  - Annular elastolytic giant cell granuloma heralding onset and recurrence of acute
      myelogenous leukemia.

PMID- 16618888
TI  - Canogenodermatoses.

PMID- 16618889
TI  - The Department of Surgery, University of Vermont College of Medicine.

PMID- 16618890
TI  - Surgeons and the Nobel Prize.

PMID- 16618891
TI  - Is right hemicolectomy for 2.0-cm appendiceal carcinoids justified?
AB  - HYPOTHESIS: We believe right hemicolectomy (RHC) is not necessary in patients
      with an appendiceal carcinoid greater than 2.0 cm. DESIGN: A retrospective review
      of patients with a histologically confirmed appendiceal carcinoid from April 1,
      1980, to February 28, 2005, and an analysis of the literature. SETTING: Tertiary
      care referral center. PATIENTS: Forty-eight patients (34 females and 14 males)
      with a histologically confirmed diagnosis of appendiceal carcinoid were included
      in the study. Appendiceal carcinoid was diagnosed incidentally in all 48
      patients. Patient ages ranged from 11 to 86 years (mean age, 41 years).
      Postoperative follow-up and disease-free survival were confirmed in 33 patients
      via medical record review. MAIN OUTCOME MEASURES: We assessed the relationship
      between survival, tumor size, and the role of RHC vs appendectomy alone. RESULTS:
      Four patients in our series underwent secondary RHC and lymph node dissection for
      tumors greater than 2.0 cm, and none had positive lymph nodes. Following review
      of the literature, we were unable to find any recent evidence of distant
      metastasis from carcinoids in patients already treated by appendectomy. There
      seem to be no conclusive data to support the notion that RHC confers a survival
      benefit over appendectomy for carcinoids greater than 2.0 cm. CONCLUSION:
      Appendiceal carcinoids greater than 2.0 cm can be managed effectively with simple
      appendectomy, given their low malignant potential and slow growth, obviating the
      need for RHC in this group of patients without affecting overall survival.

PMID- 16618892
TI  - Incidence, patterns, and prevention of wrong-site surgery.
AB  - HYPOTHESIS: We hypothesized that wrong-site surgery is infrequent and that a
      substantial proportion of such incidents are not preventable by current site
      verification protocols. DESIGN: Case series and survey of site-verification
      protocols. SETTING: Hospitals and a malpractice liability insurer. PATIENTS AND
      OTHER PARTICIPANTS: All wrong-site surgery cases reported to a large malpractice
      insurer between 1985 and 2004. MAIN OUTCOME MEASURES: Incidence, characteristics,
      and causes of wrong-site surgery and characteristics of site-verification
      protocols. RESULTS: Among 2,826,367 operations at insured institutions during the
      study period, 25 nonspine wrong-site operations were identified, producing an
      incidence of 1 in 112,994 operations (95% confidence interval, 1 in 76,336 to 1
      in 174,825). Medical records were available for review in 13 cases. Among
      reviewed claims, patient injury was permanent-significant in 1, temporary-major
      in 2, and temporary-minor or temporary-insignificant in 10. Under optimal
      conditions, the Joint Commission on Accreditation of Healthcare Organizations
      Universal Protocol might have prevented 8 (62%) of 13 cases. Hospital protocol
      design varied significantly. The protocols mandated 2 to 4 personnel to perform
      12 separate operative-site checks on average (range, 5-20). Five protocols
      required site marking in cases that involved nonmidline organs or structures; 6
      required it in all cases. CONCLUSIONS: Wrong-site surgery is unacceptable but
      exceedingly rare, and major injury from wrong-site surgery is even rarer. Current
      site-verification protocols could have prevented only two thirds of the examined
      cases. Many protocols involve considerable complexity without clear added
      benefit.

PMID- 16618893
TI  - Implications and cost of pancreatic leak following distal pancreatic resection.
AB  - OBJECTIVES: Pancreatic stump leak (PL) after elective distal pancreatic resection
      significantly impacts cost and increases subsequent health care resource
      utilization. We sought to provide an economic framework for potential
      interventions aimed at reducing its occurrence. DESIGN: Retrospective case series
      and economic evaluation. SETTING: University-affiliated, tertiary care referral
      center. PATIENTS: Sixty-six patients undergoing elective distal pancreatectomy.
      MAIN OUTCOME MEASURES: Postoperative complications; hospital and professional
      costs. RESULTS: Overall postoperative morbidity occurred in 34 patients (52%)
      with no deaths. The total number of patients with complications directly related
      to PL was 22 (33%). The mean +/- SD number of total hospital days for the no-PL
      group was 5.2 +/- 1.7 days (range, 3-12 days) vs 16.6 +/- 14.6 days (range, 4-49
      days) for the PL group (P = .001). The average patient with PL-related problems
      incurred a total cost that was 2.01 times greater than the average patient in the
      no-PL group. A decision analytic model developed to evaluate threshold costs
      showed that a hypothetical intervention designed to reduce the complication rate
      of distal pancreatectomy by one third would be financially justifiable up to a
      cost of $1418 per patient. CONCLUSIONS: Complications derived from PL following
      distal pancreatectomy double the cost and dramatically increase health care
      resource utilization. There is an urgent need to develop strategies that reduce
      the incidence of this common complication. Interventions aimed at decreasing the
      incidence of PL should take into account this cost differential. We provide an
      economic model to serve as a guide for developing these technologies.

PMID- 16618894
TI  - Short interfering RNA-mediated gene silencing of vascular endothelial growth
      factor: effects on cellular proliferation in colon cancer cells.
AB  - HYPOTHESIS: By using short interfering RNA (siRNA) to inhibit the in vitro
      expression of vascular endothelial growth factor (VEGF) A, we hope to further
      investigate the presence of an autocrine loop in colon cancer cells. We
      hypothesize that VEGF inhibition will result in decreased cellular proliferation.
      DESIGN: Human colon cancer cells were evaluated for the expression of VEGF and
      VEGF receptor 2 (VEGFR-2). In vitro assessments were then made of the ability of
      anti-VEGF siRNA to knock down expression of VEGF and the subsequent effect this
      decreased expression had on colon cancer cell proliferation. SETTING: Surgical
      oncology research laboratory. INTERVENTIONS: Human colon cancer cells from the
      RKO cell line were transfected with siRNA targeting the coding region of VEGF.
      MAIN OUTCOME MEASURES: Enzyme-linked immunosorbent assay, Northern blot analysis,
      and real-time quantitative polymerase chain reaction were performed to establish
      the ability of siRNA to decrease VEGF production. Proliferation assays were run
      on transfected and wild-type cells to establish concomitant decrease in VEGF
      expression and cellular proliferation. RESULTS: The RKO colon cancer cells
      expressed both VEGF and VEGFR-2. Those cells transfected with siRNA targeting
      VEGF showed a 94% knockdown in VEGF expression and a 67% decrease in cellular
      proliferation. CONCLUSION: Colon cancer cells expressing VEGF and VEGFR-2 may
      possess an autocrine growth pathway that can be effectively targeted using RNA
      interference as an antiangiogenic therapy.

PMID- 16618895
TI  - Long-term glycemic control and postoperative infectious complications.
AB  - HYPOTHESIS: Good preoperative glycemic control (hemoglobin A(1c) [HbA(1c)] levels
      <7%) is associated with decreased postoperative infections. DESIGN: Retrospective
      observational study using Veterans Affairs National Surgical Quality Improvement
      Program data from the Veterans Affairs Connecticut Healthcare System from January
      1, 2000, through September 30, 2003. SETTING: Veterans Affairs Connecticut
      Healthcare System, a tertiary referral center and major university teaching site.
      PATIENTS: Six hundred forty-seven diabetic patients underwent major noncardiac
      surgery during the study period; 139 were excluded because the HbA(1c) levels
      were more than 180 days prior to surgery; 19 were excluded for other reasons; 490
      diabetic patients were analyzed. The study patients were predominantly nonblack
      men with a median age of 71 years. MAIN OUTCOME MEASURES: Primary outcomes were
      infectious complications, including pneumonia, wound infection, urinary tract
      infection, or sepsis. Bivariate analysis was used first to determine the
      association of each independent variable (age, race, diabetic treatment, American
      Society of Anesthesiologists classification, Activities of Daily Living
      assessment, elective vs emergent procedure, wound classification, operation
      length, and HbA(1c) levels) with outcome. Factors significant at P<.05 were used
      in a multivariable logistic regression model. RESULTS: In the multivariable
      model, age, American Society of Anesthesiologists class, operation length, wound
      class, and HbA(1c) levels were significantly associated with postoperative
      infections. Emergency/urgent cases and dependence in Activities of Daily Living
      were significant in bivariate analysis but failed to reach statistical
      significance in the multivariable model. An HbA(1c) level of less than 7% was
      significantly associated with decreased infectious complications with an adjusted
      odds ratio of 2.13 (95% confidence interval, 1.23-3.70) and a P value of .007.
      CONCLUSION: Good preoperative glycemic control (HbA(1c) levels <7%) is associated
      with a decrease in infectious complications across a variety of surgical
      procedures.

PMID- 16618896
TI  - Reassessment of parathyroid hormone monitoring during parathyroidectomy for
      primary hyperparathyroidism after 2 preoperative localization studies.
AB  - HYPOTHESIS: For patients with primary hyperparathyroidism and patients with 2
      localization studies showing the same single location of parathyroid disease, use
      of intraoperative parathyroid hormone (IOPTH) measurement does not significantly
      increase the success of minimally invasive parathyroidectomy. DESIGN:
      Retrospective cohort study. SETTING: Experience of 2 academic centers over 5
      years (at Brigham and Women's Hospital, Boston, Mass) and almost 4 years (at
      Rhode Island Hospital, Providence). PATIENTS: A total of 569 patients with
      primary hyperparathyroidism who underwent technetium Tc 99m sestamibi (MIBI)
      parathyroid imaging and neck ultrasonography (US). MAIN OUTCOME MEASURES:
      Incidence of correct prediction of location and extent of disease. RESULTS: In
      322 patients (57%), MIBI and US imaging identified the same single site of
      disease. In 319 (99%) of these 322 patients, surgical exploration confirmed a
      parathyroid adenoma at that site, and the IOPTH levels normalized on removal. In
      3 (1%) of the 322 patients, IOPTH measurement identified unsuspected additional
      disease. In 3 (1%) of the remaining 319 patients, IOPTH-guided removal of a
      single adenoma failed to correct hypercalcemia. Therefore, the failure rate of
      surgery in patients with positive MIBI and positive US imaging was 1% with IOPTH
      measurement and 2% without IOPTH measurement (P = .50). In 201 (35%) of the 569
      patients, only 1 of the 2 studies recognized an abnormality or the studies
      disagreed on location. In these cases, either MIBI imaging or US imaging (if MIBI
      imaging was negative) failed to predict the correct site or extent of disease in
      76 (38%) of the 201 patients (P<.001 vs concordant studies). CONCLUSIONS: In
      primary hyperparathyroidism, concordant preoperative localization with MIBI and
      US imaging is highly accurate. Use of IOPTH measurement in these cases adds only
      marginal benefit. When only 1 of the 2 studies identifies disease or the studies
      conflict, however, IOPTH measurement remains essential during minimally invasive
      parathyroidectomy.

PMID- 16618897
TI  - Distal splenorenal shunt: preferred treatment for recurrent variceal hemorrhage
      in the patient with well-compensated cirrhosis.
AB  - HYPOTHESIS: Distal splenorenal shunt (DSRS) is a safe and effective treatment for
      patients with Child-Pugh class A and B cirrhosis with recurrent variceal
      hemorrhage after failed transjugular intrahepatic portosystemic shunt. DESIGN:
      Retrospective case review. SETTING: Hepatobiliary surgery and liver
      transplantation department in a tertiary referral medical center. PATIENTS:
      Between August 1, 1985, and May 1, 2005, 119 patients with Child-Pugh class A and
      B cirrhosis underwent DSRS for recurrent variceal hemorrhage. Of these, 17
      (14.3%) had thrombosed or failing transjugular intrahepatic portosystemic shunt
      prior to DSRS. INTERVENTION: Distal splenorenal shunt for recurrent variceal
      hemorrhage after failure of conservative management. MAIN OUTCOME MEASURES:
      Morbidity, mortality, and subsequent liver transplantation rate. RESULTS: The
      overall perioperative morbidity rate was 31.5%. Thirteen patients (11.7%)
      developed encephalopathy and 6 (5.4%) had recurrent variceal hemorrhage. Other
      complications included portal vein thrombosis, pancreatitis, pancreatic
      pseudocyst, pneumonia, and wound infection. The 30-day operative mortality rate
      was 6.4% (n = 7). The 1-year survival rate was 85.9%. The incidence of DSRS for
      failed transjugular intrahepatic portosystemic shunt during the first 12 years of
      the study (1985-1997) was 11.1% (9/81). This proportion increased to 26.7% (8/30)
      during the second half of the study (1997-2005). During the 20-year period, 15
      patients (13.5%) underwent liver transplantation a mean of 5.1 years after DSRS
      without an increase in morbidity or mortality after transplantation. CONCLUSIONS:
      Distal splenorenal shunt may be the preferred treatment for recurrent variceal
      hemorrhage in the patient with well-compensated cirrhosis. In addition, DSRS does
      not cause increased morbidity or mortality in subsequent liver transplantation.

PMID- 16618898
TI  - Maximizing operating room and recovery room capacity in an era of constrained
      resources.
AB  - HYPOTHESIS: Three parallel processing operating rooms (ORs) (concurrent induction
      and turnover) with a dedicated 3-bed mini-recovery room (mini-postanesthesia care
      unit [PACU]) will optimize patient throughput and main PACU workload when
      compared with 4 traditional ORs or 4 parallel processing ORs. DESIGN: Statistical
      and mathematical models projected the impact of parallel processing on case
      throughput and PACU use. SETTING: Academic medical center with 48 traditional ORs
      using serial induction and turnover and 1 experimental OR, the operating room of
      the future, with parallel processing. PARTICIPANTS: All surgical cases from
      October 2002 through March 2004 (N = 49 887). INTERVENTIONS: A statistical model
      projected the duration of induction, surgery, turnover, and PACU stay for cases
      performed in a traditional OR (n = 48 667) based on the operating room of the
      future (n = 1220) experience. A fluid queuing model compared each combination
      using specific probability density functions. MAIN OUTCOME MEASURES: Each OR
      configuration was evaluated for case throughput and minutes of work sent to the
      PACU. RESULTS: Although all cases save OR time with parallel processing, only
      select surgeon-case combinations translate time saved into additional cases per
      day (26%). Without additional PACU slots, output from 4 parallel processing ORs
      further stresses the PACU. Three parallel processing ORs and a mini-PACU balances
      incremental volume by offsetting PACU utilization in 84% of cases. CONCLUSION: In
      a PACU-constrained environment, 3 parallel processing ORs with a mini-PACU
      configuration offers increased throughput and decreased PACU workload.

PMID- 16618899
TI  - Prestorage leukoreduction prevents accumulation of matrix metalloproteinase 9 in
      stored blood.
AB  - OBJECTIVES: Transfusion of aged stored blood is associated with many neutrophil
      proinflammatory effects. The mechanism of these effects remains to be elucidated.
      The purpose of this study was to determine whether matrix metalloproteinases
      accumulate in packed red blood cells during storage and are responsible for some
      of the neutrophil proinflammatory events, and to determine whether prestorage
      leukoreduction prevents accumulation of matrix metalloproteinases and attenuates
      proinflammatory effects of stored packed red blood cells. DESIGN: Laboratory
      study. PARTICIPANTS: Healthy human volunteers. INTERVENTIONS: Units of blood were
      drawn from healthy volunteers. Half of each unit was filtered for leukoreduction,
      removing 99.9% of leukocytes. At biweekly intervals, aliquots were removed from
      packed red blood cell units, and the plasma fraction was isolated for assays.
      Plasma was assayed for specific molecules or incubated with isolated neutrophils,
      with or without a matrix metalloproteinase 9 inhibitor. MAIN OUTCOME MEASURES:
      Concentrations of matrix metalloproteinases 2 and 9 and tissue inhibitor of
      metalloproteinase 1; matrix metalloproteinase 9 activity; and neutrophil
      apoptosis. RESULTS: Concentrations of matrix metalloproteinase 9 and tissue
      inhibitor of metalloproteinase 1 but not matrix metalloproteinase 2 increased
      over time. This accumulation was abolished by leukoreduction. Matrix
      metalloproteinase 9 accumulated in an active form. Both leukoreduction and matrix
      metalloproteinase 9 inhibition reversed stored packed red blood cell-induced,
      delayed neutrophil apoptosis. CONCLUSIONS: Storage of packed red blood cells for
      14 days or more is associated with increases in the concentrations of matrix
      metalloproteinase 9 and tissue inhibitor of metalloproteinase 1, with the enzyme
      in excess of its inhibitor. Prestorage leukoreduction prevents this accumulation.
      Delayed neutrophil apoptosis related to packed red blood cell plasma appears to
      be due, in part, to matrix metalloproteinase 9. Leukoreduction can help prevent
      the effects of matrix metalloproteinase 9 on neutrophil apoptosis.

PMID- 16618900
TI  - Minimally invasive parathyroidectomy using cervical block: reasons for conversion
      to general anesthesia.
AB  - HYPOTHESIS: We investigated the frequency and reasons for conversion from
      cervical block anesthesia to general anesthesia (GA) in patients undergoing
      minimally invasive parathyroidectomy for primary hyperparathyroidism. DESIGN:
      Prospective case series. SETTING: Tertiary university hospital. PATIENTS: A total
      of 441 consecutive patients with primary hyperparathyroidism undergoing minimally
      invasive parathyroidectomy under cervical block and monitored anesthesia care
      using midazolam and narcotics were included. Patients with known multiglandular,
      familial, or secondary hyperparathyroidism or noninformative preoperative
      localization or those electing minimally invasive parathyroidectomy under GA were
      excluded. INTERVENTION: All patients underwent cervical block anesthesia and
      focused exploration using minimally invasive techniques. MAIN OUTCOME MEASURE:
      Intraoperative need for conversion from cervical block anesthesia to general
      endotracheal anesthesia. RESULTS: Of the 441 patients, 47 (10.6%) required
      conversion to GA. In all instances, conversion was performed in a controlled
      fashion using neuromuscular blockade, endotracheal intubation, and maintenance of
      the original surgical field preparation. Sixteen procedures were converted to
      accomplish simultaneous thyroid resections. An additional 15 were converted
      because the intraoperative parathyroid hormone level failed to decrease by at
      least 50% from the baseline after resection of the incident parathyroid tumor and
      extensive exploration was required. Eight procedures were converted because of
      technical difficulties related to ensuring adequate protection of the recurrent
      laryngeal nerve. Five procedures were converted to optimize patient comfort, and
      2 were converted because of the intraoperative recognition of parathyroid
      carcinoma. One patient experienced a toxic reaction to lidocaine, causing a
      seizure. CONCLUSIONS: The vast majority of minimally invasive parathyroidectomies
      can be performed using cervical block anesthesia. However, conversion to GA is
      appropriate when unexpected intraoperative findings are encountered or for
      patient comfort.

PMID- 16618901
TI  - Women in surgery: do we really understand the deterrents?
AB  - HYPOTHESIS: Women are deterred from a surgical career owing to a lack of role
      models rather than lifestyle considerations. DESIGN: Survey. SETTING: University
      teaching hospital. PARTICIPANTS: Surgery and obstetrics/gynecology attending
      physicians, residents, and medical students. INTERVENTION: Questionnaire. MAIN
      OUTCOME MEASURES: Potential deterrents to a surgical career. RESULTS: Men and
      women had a similar interest in a surgical career before their surgical rotation
      (64% vs 53%, P = .68). A similar percentage developed a mentor (40.0% vs 45.9%, P
      = .40). Women were far more likely to perceive sex discrimination (46.7% vs
      20.4%, P = .002), most often from male attending physicians (33.3%) or residents
      (31.1%). Women were less likely to be deterred by diminishing rewards (4.4% vs
      21.6%, P = .003) or workload considerations (28.9% vs 49.0%, P = .02). They were
      also less likely to cite family concerns as a deterrent (47.8% vs 66.7%, P = .02)
      and equally likely to be deterred by lifestyle during residency (83.3% vs 76.5%,
      P = .22). However, women were more likely to be deterred by perceptions of the
      "surgical personality" (40.0% vs 21.6%, P = .03) and the perception of surgery as
      an "old boys' club" (22.2% vs 3.9%, P = .002). CONCLUSIONS: Men and women are
      very similar in what they consider important in deciding on a surgical career.
      Women are not more likely to be deterred by lifestyle, workload issues, or lack
      of role models. However, the perceived surgical personality and surgical culture
      is a sex-specific deterrence to a career in surgery for women.

PMID- 16618902
TI  - Genomic approaches to surgical diseases: 21st annual Samuel Jason Mixter lecture.

PMID- 16618903
TI  - Image of the month: calcified pancreatic pseudocyst.

PMID- 16618904
TI  - Impact of sentinel node status and other risk factors on the clinical outcome of
      head and neck melanoma patients.
AB  - OBJECTIVE: To determine the impact of sentinel lymph node (SLN) status and other
      risk factors on recurrence and overall survival in head and neck melanoma
      patients. DESIGN: The SLN Working Group, based in San Francisco, Calif, with its
      11 member centers, the John Wayne Cancer Institute, and The University of Texas
      M. D. Anderson Cancer Center pooled data on 629 primary head and neck melanoma
      patients who had selective sentinel lymphadenectomy. A total of 614 subjects were
      analyzable. All centers obtained internal review board approval and adhered to
      the Health Insurance Portability and Accountability Act of 1996 regulations. A
      Cox proportional hazards model was used to identify factors associated with
      overall and disease-free survival. SETTING: Tertiary care medical centers. MAIN
      OUTCOME MEASURE: Clinical outcome of head and neck melanoma patients undergoing
      selective sentinel lymphadenectomy. RESULTS: Overall, 10.1% (n = 62) of the
      subjects had at least 1 positive node. Subjects with positive SLN status had
      significantly thicker tumors (mean thickness, 2.8 vs 2.1 mm; P < .001), and were
      more likely to have ulcerated tumors (P = .004). During the median follow-up of
      3.3 years, the overall mortality from head and neck melanoma was 10%, with more
      than 20% experiencing at least 1 recurrence. Multivariate analysis showed that
      tumor site was an independent predictor of mortality; location on the scalp had a
      more than 3-fold (P < .001) greater mortality than tumors on the face. Tumor
      thickness was also an independent predictor of overall survival, and SLN status
      was the most important predictor of disease-free survival in the multivariate
      model (P < .001). Tumors on the scalp had the highest rate of recurrence, while
      those on the neck had the lowest. Tumor ulceration was the significant predictor
      of time to recurrence or disease-free survival (P < .001). CONCLUSION: In this
      multicenter study, SLN status and other risk factors have an effect on recurrence
      and/or overall survival.

PMID- 16618905
TI  - Mucoepidermoid carcinoma of the parotid gland in children: A 10-year experience.
AB  - OBJECTIVE: To determine the presentation, pathologic features, treatment outcome,
      and prognosis of mucoepidermoid carcinoma of the parotid gland in children.
      DESIGN: Retrospective clinical and histopathologic study with institutional
      review board approval. SETTING: Tertiary pediatric medical center. PATIENTS:
      Seven children (4 girls and 3 boys) presented with mucoepidermoid carcinoma of
      the parotid gland between 1994 and 2004. MAIN OUTCOME MEASURES: Clinical
      presentation, pathologic features, treatment outcome, complications, local
      recurrence, distant metastasis, and overall survival. RESULTS: All patients
      presented with an asymptomatic parotid mass. Initial treatment in 7 patients
      included total parotidectomy (n = 3), superficial parotidectomy (n = 3),
      transoral enucleation (n = 1), and supraomohyoid neck dissection (n = 1). Four
      patients required additional surgical procedures because of a close and/or
      positive margin, including revision parotidectomy (n = 2), total parotidectomy (n
      = 1), superficial parotidectomy (n = 1), and supraomohyoid neck dissection (n =
      1). One patient required postoperative radiation therapy. No evidence of local
      recurrence or distant metastasis was noted with a mean follow-up of 3.4 years.
      CONCLUSIONS: Mucoepidermoid carcinoma of the parotid gland is very rare in
      children. Clinical stage and histologic grade are the main prognostic factors.
      Complete excision (superficial or total parotidectomy) with preservation of
      facial nerve is the treatment of choice. Neck dissection should be considered
      when there is clinical evidence of regional metastasis, high TNM stage, high
      histologic grade, and involvement of regional nodes. Because of the possibility
      of long-term adverse effects in pediatric patients, radiotherapy should be used
      only in selected cases. Long-term follow-up is essential to rule out late
      recurrence.

PMID- 16618906
TI  - Microvascular reconstruction of cranial base defects: An evaluation of
      complication and survival rates to justify the use of this repair.
AB  - OBJECTIVES: To describe our experience, including selection criteria and
      complication rates, using microvascular free tissue transfer to repair large
      skull base defects and to determine if complication rate and posttreatment
      survival justify the use of this technique. DESIGN: Retrospective review of
      clinical cohort. SETTING: Tertiary care medical center. PATIENTS: A consecutive
      sample of patients undergoing ablative surgery with repair of cranial base
      defects with free tissue transfer from 1995 to 2004. All the patients' defects
      involved intracranial exposure. MAIN OUTCOME MEASURES: Rate of local and systemic
      complications, postoperative survival, and recurrence rate. RESULTS: The study
      population comprised 40 patients. Fifteen (38%) of the patients' defects were in
      the anterior cranial base, and 26 (65%) were in the middle cranial base. We used
      5 types of free tissue flap, with a success rate of 95%. Our rate of
      perioperative mortality, meningitis, stroke, cerebrospinal fluid leak, epidural
      abscess, and osteomyelitis was 0%. We had 7 local complications and 4 systemic
      complications requiring increased length of hospital stay. Including
      microvascular problems, 12 patients had complications, for an overall
      complication rate of 30%. Follow-up ranged from 1 to 96 months, with a mean of 24
      months. The tumor recurrence rate was 30%, and disease-specific survival was 81%
      at a mean 24-month follow-up. CONCLUSIONS: We did not experience any
      perioperative mortality or intracranial morbidity. Our low complication rate in
      combination with our tumor recurrence rate and rate of patient survival justify
      the use of free tissue transfer as an option in the closure of appropriate
      cranial base defects.

PMID- 16618907
TI  - Intensification regimen for advanced-stage resectable hypopharyngeal carcinoma.
AB  - OBJECTIVE: To determine feasibility, compliance, long-term survival, and disease
      control rates in the intensification regimen for advanced resectable
      hypopharyngeal carcinoma. DESIGN: Prospective, nonrandomized, controlled phase 2
      trial with a median follow-up period of 89 months (range, 3.4-140.0 months).
      SETTING: Cancer center at a state university. PATIENTS: Thirty-two patients (age
      range, 44-79 years; median age, 59 years) with advanced (69% stage IV, 31% stage
      III) resectable hypopharyngeal carcinoma. INTERVENTIONS: Combination of surgery,
      radiation therapy, and chemotherapy (cisplatin and paclitaxel) along with
      intraoperative radiation therapy. MAIN OUTCOME MEASURES: Compliance, long-term
      survival, and locoregional and systemic disease control rates and functional
      outcome. RESULTS: The protocol compliance rate was 62% (20 of 32 patients), and
      the overall 5-year survival rate was 56%. Local recurrence occurred in 3 patients
      (9%). The systemic disease control rate was 91% (29 of 32 patients). Total
      laryngectomy was required in 15 patients (47%); preservation of the larynx was
      possible in 17 patients (53%). Only 3 (13%) of 6 patients were percutaneous
      endoscopic gastrostomy tube dependent in the long-term follow-up. CONCLUSIONS:
      The intensification regimen described in this study accomplished excellent long
      term survival and disease control rates in patients with advanced resectable
      hypopharyngeal carcinoma. The future plan is to proceed with a phase 3 trial if
      the single-institutional experience at The Ohio State University can be
      duplicated in a multi-institutional phase 2 study.

PMID- 16618908
TI  - Serum protein profile analysis in patients with head and neck squamous cell
      carcinoma.
AB  - OBJECTIVES: To analyze surface-enhanced laser desorption and ionization time-of
      flight mass spectrometry (SELDI-TOF-MS) protein profiles of patients with head
      and neck squamous cell carcinoma (HNSCC) and healthy controls and to determine
      the sensitivity and specificity of SELDI assay for HNSCC detection before and
      after treatment. DESIGN: Proteomic analysis and comparison of serum samples.
      SETTING: Tertiary care academic medical center. SUBJECTS: Seventy-eight patients
      with HNSCC and 68 healthy controls. MAIN OUTCOME MEASURES: Serum samples were
      prospectively collected from 78 patients with HNSCC and 68 healthy control
      volunteers. SELDI-TOF-MS was performed on serum samples to identify protein peaks
      in the range of 0 to 100 kDa. Classification analysis of the spectral data was
      performed and used to classify the disease status of the patients. RESULTS: The
      SELDI-TOF-MS assay generated serum protein profiles ranging from 0 to 100 kDa.
      After background subtraction, mass calibration, and normalization, 545 protein
      peaks were identified. Classification tree analysis based on peak expression
      correctly classified patients with HNSCC with 82% sensitivity and 76%
      specificity. Subgroup analysis correctly classified 83% of oral cavity tumors,
      81% of oropharyngeal tumors, and 88% of laryngeal tumors. Pretreatment and
      posttreatment samples were available from 12 patients, and the posttreatment
      samples were correctly classified in 86% of the patients at 3 months and 75% of
      the patients at 6 months. CONCLUSIONS: Proteomic SELDI-TOF-MS analysis of serum
      protein profiles distinguishes patients with HNSCC from controls with a high
      degree of sensitivity and specificity. Further investigation into the clinical
      utility of this technology in HNSCC detection and surveillance is warranted.

PMID- 16618909
TI  - Revision cochlear implantation for facial nerve stimulation in otosclerosis.
AB  - OBJECTIVE: To find if patients experiencing postsurgical facial nerve stimulation
      caused by underlying disease process (ie, otosclerosis) can improve their hearing
      performance with their cochlear implant by reimplantation and by an optimal
      programming strategy. DESIGN: Retrospective analysis. SETTING: Academic tertiary
      referral center. PATIENTS: Two cochlear otosclerosis patients with resistant
      facial nerve stimulation (FNS). Both patients were initially implanted with
      Nucleus 22 devices (Cochlear Corporation, Englewood, Colo) and they developed FNS
      after a period of use. Owing to the decreasing number of active electrodes,
      concurrent decreases in speech understanding occurred. INTERVENTIONS: Various
      programming approaches were used to address the FNS. Both subjects ultimately
      received Nucleus 24 devices. One was reimplanted in the same ear, and the other
      was implanted in the opposite ear. Both have been followed up for 8 months
      following the reimplantation. MAIN OUTCOME MEASURES: Cochlear implant programming
      levels, cochlear implant performance, and facial nerve stimulation. RESULTS: The
      FNS was managed for more than 3 years through optimized programming. However, the
      FNS progressed until performance dropped below acceptable levels. Reimplantation
      was believed to be the only option for improvement. After reimplantation and
      programming, both subjects showed immediate improvement in speech discrimination.
      One user increased his consonant-nucleus-consonant word score from 12%
      preoperatively to 42%, and the other's performance increased from 0% to 86%.
      CONCLUSIONS: Our results suggest that having more programming options with newer
      devices is critical in otosclerotic or ossified users who experience FNS. Also,
      reimplantation may be a useful tool to improve performance.

PMID- 16618910
TI  - Fine-mapping loss of gene architecture at the CDKN2B (p15INK4b), CDKN2A (p14ARF,
      p16INK4a), and MTAP genes in head and neck squamous cell carcinoma.
AB  - OBJECTIVE: To identify the extent and the smallest region of loss for
      CDKN2B(INK4b), CDKN2A(ARF,INK4a), and MTAP. Homozygous deletions of human
      chromosome 9p21 occur frequently in malignant cell lines and are common in
      squamous cell carcinoma of the head and neck (HNSCC). This complex region encodes
      the tumor suppressor genes cyclin-dependent kinase 2B (CDKN2B) (p15(INK4b)) and
      CDKN2A (p14(ARF), p16(INK4a)) and the housekeeping gene methylthioadenosine
      phosphorylase (MTAP). DESIGN: A targeted probe panel designed to finely map the
      region of 9p21 loss comprised 3 probes for CDKN2B(INK4b), 7 for CDKN2A(ARF,
      INK4a), and 3 for MTAP and was interrogated using the multiplex ligation
      dependent probe amplification assay (MLPA). The MLPA genomic copy number
      alterations for CDKN2A were validated using real-time polymerase chain reaction.
      SUBJECTS: Six HNSCC primary (A) and recurrent or metastatic (B) cell lines were
      examined: UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B. RESULTS: Cell line
      UMSCC-11B retained all 9p loci tested in the region. Cell lines UMSCC-17A/B
      indicated homozygous deletion of CDKN2A(ARF, INK4a) starting at p16(INK4) exon
      1alpha to include exons 2 and 3. Homozygous loss was indicated for CDKN2B(INK4b)
      and CDKN2A(ARF,INK4a) in UMSCC-11A, and UMSCC-81A. Cell line UMSCC-81B indicated
      retention of all 9p loci except for exon 1alpha (p16(INK4a)). Selective loss of
      the 3' end of MTAP was observed in UMSCC-11A. Genomic alterations by fine-mapping
      MLPA were validated at the DNA level for CDKN2A. CONCLUSIONS: We identified exon
      1alpha (p16(INK4a)) as the smallest region of loss in the CDKN2A(ARF, INK4a)
      gene. The frequency and precise loss of CDKN2B(INK4b), CDKN2A(ARF, INK4a), and
      MTAP in the prognosis of 9p21-deleted HNSCC may provide impetus for use of these
      targets as therapeutic biomarkers in head and neck cancer.

PMID- 16618911
TI  - Chromosomal mapping and phenotypic characterization of hereditary otosclerosis
      linked to the OTSC4 locus.
AB  - OBJECTIVE: To perform chromosomal mapping and clinical analysis of hereditary
      otosclerosis linked to the fourth locus for otosclerosis (OTSC4) in an Israeli
      family. DESIGN: Pedigree study. SETTING: A genetics of hearing loss research
      laboratory, a clinical genetics laboratory, a center for speech and hearing, and
      an otolaryngology department at a university and medical centers in Israel.
      SUBJECTS: An Israeli family of which 24 members were ascertained and a pedigree
      was constructed; 12 members had otosclerosis. INTERVENTIONS: Confirmation of
      otosclerosis by surgery (3 subjects) and by audiologic evaluation, medical
      history, and family history (9 subjects), and whole-genome scanning to identify
      the chromosomal region of the mutant locus. MAIN OUTCOME MEASURES: Chromosomal
      location of the otosclerosis locus. RESULTS: Linkage to the 16q21-23.2 interval
      was identified and confirmed with a logarithm of odds (LOD) score of 3.97 at
      theta = 0. The new locus for otosclerosis was designated OTSC4. The OTSC4
      interval of 9 to 10 megabase includes several genes involved in the immune system
      and bone homeostasis that may be good candidates for genes otosclerosis.
      CONCLUSION: The elucidation of the OTSC4 gene may disclose the etiology of the
      disorder, and the functional and structural analysis of the protein may open new
      options for diagnosis, treatment, and prevention of otosclerosis.

PMID- 16618912
TI  - Temperature-controlled radiofrequency treatment of tonsillar hypertrophy for
      reduction of upper airway obstruction in pediatric patients.
AB  - OBJECTIVES: To determine if temperature-controlled radiofrequency (TCRF) tonsil
      reduction and adenoidectomy (TCRF&A) and conventional tonsillectomy and
      adenoidectomy (T&A) are statistically similar in outcome and to compare morbidity
      between TCRF&A and conventional T&A. DESIGN: Randomized control trial. SETTING:
      Tertiary care children's hospital. PARTICIPANTS: The study population comprised
      23 patients aged 2.6 to 12.5 years with symptoms of obstructive sleep apnea,
      hypertrophic tonsils with no other areas of upper airway obstruction with the
      exception of hypertrophic adenoids, and a body mass index (calculated as weight
      in kilograms divided by the square of height in meters) of less than 30.
      INTERVENTION: Temperature-controlled radiofrequency tonsil reduction (mean +/-
      SD, 12.6 +/- 1.5 ablations per patient and 994.68 +/- 91.88 J per insertion) and
      adenoidectomy or traditional bovie T&A. MAIN OUTCOME MEASURES: Primary outcomes
      were respiratory distress index and total volume reduction. Secondary outcomes
      include postoperative pain, daytime sleepiness, speech and swallowing problems,
      weight and diet, narcotic use, and analogue snoring scale. RESULTS: The
      respiratory distress index difference for TCRF&A was 5.63 vs 6.56 for standard
      T&A. On postoperative day 1 for the 13 patients who underwent TCRF&A, 0 reported
      severe pain, 11 (85%) had mild to moderate pain, and 2 (15%) had no pain. In the
      10 patients who underwent standard T&A, 1 (10%) had severe pain and 9 (90%) had
      mild to moderate pain. By postoperative week 1, all TCRF&A patients experienced
      mild or no pain, whereas 1 (10%) of the standard T&A patients still had moderate
      pain. Mean visual analogue snore scores (0-10) 4 weeks after surgery were less
      than 1 for both groups. The mean +/- SD weight loss at postoperative week 1 for
      TCRF tonsil reduction patients was 1.0 +/- 3.5 lb (0.45 +/- 1.58 kg) vs 4.6 +/-
      3.9 lb (2.07 +/- 1.76 kg) for standard T&A patients. Return to normal diet at
      postoperative week 1 occurred in 11 TCRF&A patients (85%) and 0 standard T&A
      patients. CONCLUSIONS: The respiratory distress indexes were similar for TCRF&A
      patients and standard T&A patients. In addition, there were similar analog
      snoring scales, decreased pain, and weight loss.

PMID- 16618913
TI  - Obstructive sleep apnea: Should all children with Down syndrome be tested?
AB  - OBJECTIVES: To determine the incidence of obstructive sleep apnea syndrome in
      children aged 2 to 4 years with Down syndrome and to determine parents' ability
      to predict sleep abnormalities in this patient population. DESIGN: Prospective
      cohort study. SETTING: Tertiary care pediatric referral center. PATIENTS: Sixty
      five children participating in a 5-year longitudinal study in which the
      otolaryngologic problems seen in Down syndrome were evaluated. Fifty-six
      completed overnight polysomnography (PSG) between 4 and 63 months of age (mean
      age, 42 months). INTERVENTIONS: Overnight PSG was performed. Parents also
      completed a questionnaire regarding their impressions of their child's sleep
      patterns before PSG. MAIN OUTCOME MEASURES: Polysomnograms were classified as
      abnormal if the obstructive index was greater than 1, if the carbon dioxide level
      was greater than 45 mm Hg for more than two thirds of the study or greater than
      50 mm Hg for more than 10% of the study, and/or if there was unexpected hypoxemia
      less than 92% during sleep or repeated intermittent desaturations less than 90%.
      We also identified a group of children whose PSGs findings were normal except for
      an arousal index greater than 10 and were associated with increased work of
      breathing. RESULTS: The PSGs revealed that 57% of the children had abnormal
      results and evidence of obstructive sleep apnea syndrome. If we also include an
      elevated arousal index, 80% of the PSGs had abnormal results. Sixty-nine percent
      of parents reported no sleep problems in their children, but in this group, 54%
      of PSGs had abnormal results. Of the parents who reported sleep problems in their
      children, only 36% had abnormal sleep study results. CONCLUSION: Because of the
      high incidence of obstructive sleep apnea syndrome in young children with Down
      syndrome, and the poor correlation between parental impressions of sleep problems
      and PSG results, baseline PSG is recommended in all children with Down syndrome
      at age 3 to 4 years.

PMID- 16618914
TI  - Relief of upper airway obstruction with mandibular distraction surgery: Long-term
      quantitative results in young children.
AB  - OBJECTIVE: To evaluate the long-term benefits of mandibular distraction on sleep
      related upper airway obstruction in young children with mandibular hypoplasia.
      DESIGN: Cross-sectional study. Subjects were examined for sleep-disordered
      breathing using medical history, physical examination results, and a written
      questionnaire. Subjects underwent standard overnight polysomnography, during
      which measures of sleep-disordered breathing were collected. SETTING: Tertiary
      care hospital. PATIENTS: Five children with upper airway obstruction from
      craniofacial anomalies treated with mandibular distraction, with a minimum follow
      up of 12 months. MAIN OUTCOME MEASURES: Apnea-hypopnea index, oxygen saturation
      nadir, and peak end-tidal carbon dioxide value. RESULTS: Of the 5 children, 3
      were cured of upper airway obstruction as documented by polysomnography, with an
      apnea-hypopnea index of less than 1.5 and no snoring. The fourth child had
      primary snoring without apnea. The fifth child had severe obstructive sleep
      apnea, with an apnea-hypopnea index of 20.2. CONCLUSIONS: Most children who
      undergo mandibular distraction for upper airway obstruction associated with
      mandibular hypoplasia demonstrate significant clinical improvement of obstructive
      sleep apnea. However, those children who continue to have symptoms of sleep
      disordered breathing after surgery should undergo polysomnography for evaluation
      of persistent obstructive sleep apnea.

PMID- 16618915
TI  - Effect of telithromycin and azithromycin on nasopharyngeal bacterial flora in
      patients with acute maxillary sinusitis.
AB  - OBJECTIVE: To explore the efficacy of the ketolide telithromycin compared with
      azithromycin in eradicating S pneumoniae from the nasopharynx of adults with
      acute maxillary sinusitis. The growing resistance of Streptococcus pneumoniae to
      penicillin and macrolides brought about the development of a new class of
      antibiotics-the ketolides-that are effective against resistant pneumococci.
      SETTING: Otolaryngology clinic. PATIENTS: One-hundred five patients with acute
      maxillary sinusitis. INTERVENTIONS: Nasopharyngeal cultures were obtained before
      therapy and 10 to 12 days after initiation of treatment. Fifty-nine patients were
      treated with 500 mg of azithromycin daily for 3 days and 46 were treated with 800
      mg of telithromycin daily for 5 days. RESULTS: Sixty-seven potential pathogens
      were recovered prior to initiation of therapy in 57 patients, 32 treated with
      telithromycin and 25 treated with azithromycin: S pneumoniae (31 isolates),
      Haemophilus influenzae (non-type b) (13), Staphylococcus aureus (8),
      Streptococcus pyogenes (8), and Moraxella catarrhalis (7). The distribution of
      the pathogens was similar in both groups. The number of S pneumoniae isolates in
      the azithromycin group was reduced following treatment from 14 to 8 (43%
      reduction), and 5 of these 8 isolates were resistant to azithromycin. In
      contrast, the number of S pneumoniae isolates in the telithromycin group was
      reduced following treatment from 17 to 1 (94% reduction) (P < .01). This isolate
      was susceptible to azithromycin and telithromycin. No differences were noted in
      the eradication rate of all of the other potential pathogens, which were all
      susceptible to both azithromycin and telithromycin. Development of resistance to
      the antimicrobial agents used (defined as increase in the minimal inhibitory
      concentration by at least 2 tubes) was found only in 5 isolates (4 S pneumoniae
      and 1 H influenzae) recovered only from patients who received azithromycin (P <
      .05). CONCLUSION: These data illustrate the superiority of telithromycin to
      azithromycin in the eradication of S pneumoniae from the nasopharynx.

PMID- 16618916
TI  - Evaluation and management of pediatric oropharyngeal trauma.
AB  - OBJECTIVE: To examine the clinical factors that influence medical decision making
      in children with oropharyngeal trauma. DESIGN: Retrospective chart review
      (spanning 6 years). SETTING: Tertiary care children's hospital. PATIENTS: One
      hundred seven consecutive children with traumatic oropharyngeal injuries.
      INTERVENTIONS: Computed tomographic angiography (CTA) (n = 52), surgical therapy
      (n = 16), inpatient admission (n = 44), and antibiotic administration (n = 77).
      MAIN OUTCOME MEASURES: The likelihood of a patient undergoing each of the 4
      interventions and having positive radiographic findings or clinical complications
      was assessed with respect to the following clinical factors: (1) age, (2) sex,
      (3) mechanism of injury, (4) site of injury, (5) wound severity (3-point scale),
      and (6) otolaryngology consultation. RESULTS: The following factors were
      significantly associated with an increased likelihood of a patient undergoing CTA
      to rule out occult internal carotid artery damage: (1) injury to the lateral soft
      palate, (2) high wound severity score, and (3) otolaryngology consultation.
      Radiographic abnormalities (including free air, parapharyngeal edema, and
      hematoma) were present in 16 (31%) of 52 CTAs but were not associated with any
      specific clinical factors. Patients with more severe wounds were more likely to
      undergo CTA, go to the operating room, receive antibiotics, and be admitted to
      the hospital but were not more likely to have positive CTA findings or an adverse
      clinical outcome. CONCLUSIONS: We were unable to identify any clinical factors
      that would help predict which children with oropharyngeal trauma are at high risk
      of developing neurologic sequelae. Radiographic screening for vascular injury in
      children with oropharyngeal trauma remains controversial.

PMID- 16618917
TI  - Radiology quiz case: Tracheal bronchus.

PMID- 16618918
TI  - Pathology quiz case: Sinus histiocytosis with massive lymphadenopathy (Rosai
      Dorfman disease).

PMID- 16618919
TI  - The decline of cross-species intersensory perception in human infants.
AB  - Between 6 and 10 months of age, infants become better at discriminating among
      native voices and human faces and worse at discriminating among nonnative voices
      and other species' faces. We tested whether these unisensory perceptual narrowing
      effects reflect a general ontogenetic feature of perceptual systems by testing
      across sensory modalities. We showed pairs of monkey faces producing two
      different vocalizations to 4-, 6-, 8-, and 10-month-old infants and asked whether
      they would prefer to look at the corresponding face when they heard one of the
      two vocalizations. Only the two youngest groups exhibited intersensory matching,
      indicating that perceptual narrowing is pan-sensory and a fundamental feature of
      perceptual development.

PMID- 16618920
TI  - Structural plasticity of an aminoacyl-tRNA synthetase active site.
AB  - Recently, tRNA aminoacyl-tRNA synthetase pairs have been evolved that allow one
      to genetically encode a large array of unnatural amino acids in both prokaryotic
      and eukaryotic organisms. We have determined the crystal structures of two
      substrate-bound Methanococcus jannaschii tyrosyl aminoacyl-tRNA synthetases that
      charge the unnatural amino acids p-bromophenylalanine and 3-(2-naphthyl)alanine
      (NpAla). A comparison of these structures with the substrate-bound WT synthetase,
      as well as a mutant synthetase that charges p-acetylphenylalanine, shows that
      altered specificity is due to both side-chain and backbone rearrangements within
      the active site that modify hydrogen bonds and packing interactions with
      substrate, as well as disrupt the alpha8-helix, which spans the WT active site.
      The high degree of structural plasticity that is observed in these aminoacyl-tRNA
      synthetases is rarely found in other mutant enzymes with altered specificities
      and provides an explanation for the surprising adaptability of the genetic code
      to novel amino acids.

PMID- 16618921
TI  - An endangered oasis of aquatic microbial biodiversity in the Chihuahuan desert.
AB  - The Cuatro Cienegas basin in the Chihuahuan desert is a system of springs,
      streams, and pools. These ecosystems support >70 endemic species and abundant
      living stromatolites and other microbial communities, representing a desert oasis
      of high biodiversity. Here, we combine data from molecular microbiology and
      geology to document the microbial biodiversity of this unique environment. Ten
      water samples from locations within the Cuatro Cienegas basin and two neighboring
      valleys as well as three samples of wet sediments were analyzed. The phylogeny of
      prokaryotic populations in the samples was determined by characterizing cultured
      organisms and by PCR amplification and sequencing of 16S rRNA genes from total
      community DNA. The composition of microbial communities was also assessed by
      determining profiles of terminal restriction site polymorphisms of 16S rRNA genes
      in total community DNA. There were 250 different phylotypes among the 350
      cultivated strains. Ninety-eight partial 16S rRNA gene sequences were obtained
      and classified. The clones represented 38 unique phylotypes from ten major
      lineages of Bacteria and one of Archaea. Unexpectedly, 50% of the phylotypes were
      most closely related to marine taxa, even though these environments have not been
      in contact with the ocean for tens of millions of years. Furthermore, terminal
      restriction site polymorphism profiles and geological data suggest that the
      aquatic ecosystems of Cuatro Cienegas are hydrologically interconnected with
      adjacent valleys recently targeted for agricultural intensification. The findings
      underscore the conservation value of desert aquatic ecosystems and the urgent
      need for study and preservation of freshwater microbial communities.

PMID- 16618922
TI  - Domain architecture and structure of the bacterial cell division protein DivIB.
AB  - Bacterial cytokinesis requires the coordinated assembly of a complex of proteins,
      collectively known as the divisome, at the incipient division site. DivIB/FtsQ is
      a conserved component of the divisome in bacteria with cell walls, suggesting
      that it plays a role in synthesis and/or remodeling of septal peptidoglycan. We
      demonstrate that the extracytoplasmic region of DivIB comprises three discrete
      domains that we designate alpha, beta, and gamma from the N to C terminus. The
      alpha-domain is proximal to the cytoplasmic membrane and coincident with the
      polypeptide transport-associated domain that was proposed previously to function
      as a molecular chaperone. The beta-domain has a unique 3D fold, with no
      eukaryotic counterpart, and we show that it interconverts between two discrete
      conformations via cis-trans isomerization of a Tyr-Pro peptide bond. We propose
      that this isomerization might modulate protein-protein interactions of the
      flanking alpha- and gamma-domains. The C-terminal gamma-domain is unstructured in
      the absence of other divisomal proteins, but we show that it is critical for
      DivIB function.

PMID- 16618923
TI  - Extensive individual variation in L1 retrotransposition capability contributes to
      human genetic diversity.
AB  - Despite being scarce in the human genome, active L1 retrotransposons continue to
      play a significant role in its evolution. Because of their recent expansion, many
      L1s are not fixed in humans, and, when present, their mobilization potential can
      vary among individuals. Previously, we showed that the great majority of
      retrotransposition events in humans are caused by highly active, or hot, L1s.
      Here, in four populations of diverse geographic origins (160 haploid genomes), we
      investigated the degree of sequence polymorphism of three hot L1s and the extent
      of individual variation in mobilization capability of their allelic variants. For
      each locus, we found one previously uncharacterized allele in every three to five
      genomes, including some with nonsense and insertion/deletion mutations. Single or
      multiple nucleotide substitutions drastically affected the retrotransposition
      efficiency of some alleles. One-third of elements were no longer hot, and these
      so-called cool alleles substantially increased the range of individual
      susceptibility to retrotransposition events. Adding the activity of the three
      elements in each individual resulted in a surprising degree of variation in
      mobilization capability, ranging from 0% to 390% of a reference L1. These data
      suggest that individual variation in retrotransposition potential makes an
      important contribution to human genetic diversity.

PMID- 16618924
TI  - Genes for the peptidoglycan synthesis pathway are essential for chloroplast
      division in moss.
AB  - The general consensus is that a cyanobacterium phagocytosed by a host cell
      evolved into the plastids of red and green algae, land plants, and glaucophytes.
      In contrast to the plastids of glaucophytes, which retain a cyanobacterial-type
      peptidoglycan layer, no wall-like structures have been detected in plastids from
      other sources. Although the genome of Arabidopsis thaliana contains five genes
      that are essential for peptidoglycan synthesis, MurE, MurG, two genes for D-Ala-D
      Ala ligase (Ddl), and the gene for translocase I (MraY), their functions have not
      been determined. We report that the moss Physcomitrella patens has nine
      homologous genes related to peptidoglycan biosynthesis: MurA, B, C, D, E, and F,
      Ddl, genes for the penicillin-binding protein Pbp, and dd-carboxypeptidase (Dac).
      Corroborating a computer prediction, analysis of the GFP fusion proteins with the
      N terminus of PpMurE or of PpPbp suggests that these proteins are located in the
      chloroplasts. Gene disruption of the PpMurE gene in P. patens resulted in the
      appearance of macrochloroplasts both in protonema and in leaf cells. Moreover,
      gene knockout of the P. patens Pbp gene showed inhibition of chloroplast division
      in this moss; however, no Pbp gene was found in A. thaliana.

PMID- 16618925
TI  - Activity-dependent release of precursor nerve growth factor, conversion to mature
      nerve growth factor, and its degradation by a protease cascade.
AB  - In this report, we provide direct demonstration that the neurotrophin nerve
      growth factor (NGF) is released in the extracellular space in an activity
      dependent manner in its precursor form (proNGF) and that it is in this
      compartment that its maturation and degradation takes place because of the
      coordinated release and the action of proenzymes and enzyme regulators. This
      converting protease cascade and its endogenous regulators (including tissue
      plasminogen activator, plasminogen, neuroserpin, precursor matrix
      metalloproteinase 9, and tissue inhibitor metalloproteinase 1) are colocalized in
      neurons of the cerebral cortex and released upon neuronal stimulation. We also
      provide evidence that this mechanism operates in in vivo conditions, as the CNS
      application of inhibitors of converting and degrading enzymes lead to dramatic
      alterations in the tissue levels of either precursor NGF or mature NGF.
      Pathological alterations of this cascade in the CNS might cause or contribute to
      a lack of proper neuronal trophic support in conditions such as cerebral
      ischemia, seizure and Alzheimer's disease or, conversely, to excessive local
      production of neurotrophins as reported in inflammatory arthritis pain.

PMID- 16618926
TI  - Optically directed molecular transport and 3D isoelectric positioning of
      amphoteric biomolecules.
AB  - We demonstrate the formation of charged molecular packets and their transport
      within optically created electrical force-field traps in a pH-buffered
      electrolyte. We call this process photoelectrophoretic localization and transport
      (PELT). The electrolyte is in contact with a photoconductive semiconductor
      electrode and a counterelectrode that are connected through an external circuit.
      A light beam directed to coordinates on the photoconductive electrode surface
      produces a photocurrent within the circuit and electrolyte. Within the
      electrolyte, the photocurrent creates localized force-field traps centered at the
      illuminated coordinates. Charged molecules, including polypeptides and proteins,
      electrophoretically accumulate into the traps and subsequently can be transported
      in the electrolyte by moving the traps over the photoconductive electrode in
      response to movement of the light beam. The molecules in a single trap can be
      divided into aliquots, and the aliquots can be directed along multiple routes
      simultaneously by using multiple light beams. This photoelectrophoretic transport
      of charged molecules by PELT resembles the electrostatic transport of electrons
      within force-field wells of solid-state charge-coupled devices. The molecules,
      however, travel in a liquid electrolyte rather than a solid. Furthermore, we have
      used PELT to position amphoteric biomolecules in three dimensions. A 3D pH
      gradient was created in an electrolyte medium by controlling the illumination
      position on a photoconductive anode where protons were generated
      electrolytically. Photoelectrophoretic transport of amphoteric molecules through
      the pH gradient resulted in accumulation of the molecules at their apparent 3D
      isoelectric coordinates in the medium.

PMID- 16618927
TI  - Histone and DNA methylation defects at Hox genes in mice expressing a SET domain
      truncated form of Mll.
AB  - The Mll gene is a member of the mammalian trithorax group, involved with the
      antagonistic Polycomb group in epigenetic regulation of homeotic genes. MLL
      contains a highly conserved SET domain also found in various chromatin proteins.
      In this study, we report that mice in which this domain was deleted by homologous
      recombination in ES cells (DeltaSET) exhibit skeletal defects and altered
      transcription of particular Hox genes during development. Chromatin
      immunoprecipitation and bisulfite sequencing analysis on developing embryo
      tissues demonstrate that this change in gene expression is associated with a
      dramatic reduction in histone H3 Lysine 4 monomethylation and DNA methylation
      defects at the same Hox loci. These results establish in vivo that the major
      function of Mll is to act at the chromatin level to sustain the expression of
      selected target Hox genes during embryonic development. These observations
      provide previously undescribed evidence for the in vivo relationship and SET
      domain dependence between histone methylation and DNA methylation on MLL target
      genes during embryonic development.

PMID- 16618928
TI  - Designing a nano-interface in a microfluidic chip to probe living cells:
      challenges and perspectives.
AB  - Nanotechnology-based materials are beginning to emerge as promising platforms for
      biomedical analysis, but measurement and control at the cell-chip interface
      remain challenging. This idea served as the basis for discussion in a focus group
      at the recent National Academies Keck Futures Initiative. In this Perspective, we
      first outline recent advances and limitations in measuring nanoscale mechanical,
      biochemical, and electrical interactions at the interface between biomaterials
      and living cells. Second, we present emerging experimental and conceptual
      platforms for probing living cells with nanotechnology-based tools in a
      microfluidic chip. Finally, we explore future directions and critical needs for
      engineering the cell-chip interface to create an integrated system capable of
      high-resolution analysis and control of cellular physiology.

PMID- 16618929
TI  - Mapping the Arabidopsis organelle proteome.
AB  - A challenging task in the study of the secretory pathway is the identification
      and localization of new proteins to increase our understanding of the functions
      of different organelles. Previous proteomic studies of the endomembrane system
      have been hindered by contaminating proteins, making it impossible to assign
      proteins to organelles. Here we have used the localization of organelle proteins
      by the isotope tagging technique in conjunction with isotope tags for relative
      and absolute quantitation and 2D liquid chromatography for the simultaneous
      assignment of proteins to multiple subcellular compartments. With this approach,
      the density gradient distributions of 689 proteins from Arabidopsis thaliana were
      determined, enabling confident and simultaneous localization of 527 proteins to
      the endoplasmic reticulum, Golgi apparatus, vacuolar membrane, plasma membrane,
      or mitochondria and plastids. This parallel analysis of endomembrane components
      has enabled protein steady-state distributions to be determined. Consequently,
      genuine organelle residents have been distinguished from contaminating proteins
      and proteins in transit through the secretory pathway.

PMID- 16618930
TI  - Profile of C. David Allis.

PMID- 16618931
TI  - Archaeal mysteries of the deep revealed.

PMID- 16618932
TI  - Arf gene loss enhances oncogenicity and limits imatinib response in mouse models
      of Bcr-Abl-induced acute lymphoblastic leukemia.
AB  - Mouse bone marrow cells transduced with retroviral vectors encoding either of two
      oncogenic Bcr-Abl isoforms (p210(Bcr-Abl) and p185(Bcr-Abl)) induce B cell
      lympholeukemias when transplanted into lethally irradiated mice. If the activity
      of the Arf tumor suppressor is compromised, these donor cells initiate a much
      more highly aggressive and rapidly fatal disease. When mouse bone marrow cells
      expressing Bcr-Abl are placed in short-term cultures selectively designed to
      support the outgrowth of pre-B cells, only those lacking one or two Arf alleles
      can initiate lympholeukemias when inoculated into immunocompetent, syngeneic
      recipient mice. Although the ABL kinase inhibitor imatinib mesylate (Gleevec)
      provides highly effective treatment for BCR-ABL-positive chronic myelogenous
      leukemia, it has proven far less efficacious in the treatment of BCR-ABL-positive
      acute lymphoblastic leukemias (ALLs), many of which sustain deletions of the
      INK4A-ARF (CDKN2A) tumor suppressor locus. Mice receiving Arf-/- or Arf+/-
      p210(Bcr-Abl)-positive pre-B cells do not achieve remission when maintained on
      high doses of oral imatinib therapy and rapidly succumb to lympholeukemia.
      Although cells expressing the Bcr-Abl kinase can proliferate in the absence of IL
      7, they remain responsive to this cytokine, which can reduce their sensitivity to
      imatinib. Treatment of Arf-/-, p210(Bcr-Abl)-positive pre-B cells with imatinib
      together with an inhibitor of JAK kinases abrogates this resistance, suggesting
      that this combination may prove beneficial in the treatment of BCR-ABL-positive
      acute lymphoblastic leukemia.

PMID- 16618933
TI  - Neuregulin 1 transcripts are differentially expressed in schizophrenia and
      regulated by 5' SNPs associated with the disease.
AB  - Genetic variation in neuregulin 1 (NRG1) is associated with schizophrenia. The
      disease-associated SNPs are noncoding, and their functional implications remain
      unknown. We hypothesized that differential expression of the NRG1 gene explains
      its association to the disease. We examined four of the disease-associated SNPs
      that make up the original risk haplotype in the 5' upstream region of the gene
      for their effects on mRNA abundance of NRG1 types I-IV in human postmortem
      hippocampus. Diagnostic comparisons revealed a 34% increase in type I mRNA in
      schizophrenia and an interaction of diagnosis and genotype (SNP8NRG221132) on
      this transcript. Of potentially greater interest, a single SNP within the risk
      haplotype (SNP8NRG243177) and a 22-kb block of this core haplotype are associated
      with mRNA expression for the novel type IV isoform in patients and controls.
      Bioinformatic promoter analyses indicate that both SNPs lead to a gain/loss of
      putative binding sites for three transcription factors, serum response factor,
      myelin transcription factor-1, and High Mobility Group Box Protein-1. These data
      implicate variation in isoform expression as a molecular mechanism for the
      genetic association of NRG1 with schizophrenia.

PMID- 16618934
TI  - Trembley's polyps go transgenic.

PMID- 16618935
TI  - Quantitative genetics of age at reproduction in wild swans: support for
      antagonistic pleiotropy models of senescence.
AB  - Why do individuals stop reproducing after a certain age, and how is this age
      determined? The antagonistic pleiotropy theory for the evolution of senescence
      predicts that increased early-life performance should be accompanied by earlier
      (or faster) senescence. Hence, an individual that has started to breed early
      should also lose its reproductive capacities early. We investigate here the
      relationship between age at first reproduction (AFR) and age at last reproduction
      (ALR) in a free-ranging mute swan (Cygnus olor) population monitored for 36
      years. Using multivariate analyses on the longitudinal data, we show that both
      traits are strongly selected in opposite directions. Analysis of the phenotypic
      covariance between these characters shows that individuals vary in their inherent
      quality, such that some individuals have earlier AFR and later ALR than expected.
      Quantitative genetic pedigree analyses show that both traits possess additive
      genetic variance but also that AFR and ALR are positively genetically correlated.
      Hence, although both traits display heritable variation and are under opposing
      directional selection, their evolution is constrained by a strong evolutionary
      tradeoff. These results are consistent with the theory that increased early-life
      performance comes with faster senescence because of genetic tradeoffs.

PMID- 16618936
TI  - Crystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key
      enzyme in glutathione metabolism, and its reaction intermediate.
AB  - Gamma-glutamyltranspeptidase (GGT) is a heterodimic enzyme that is generated from
      the precursor protein through posttranslational processing and catalyzes the
      hydrolysis of gamma-glutamyl bonds in gamma-glutamyl compounds such as
      glutathione and/or the transfer of the gamma-glutamyl group to other amino acids
      and peptides. We have determined the crystal structure of GGT from Escherichia
      coli K-12 at 1.95 A resolution. GGT has a stacked alphabetabetaalpha fold
      comprising the large and small subunits, similar to the folds seen in members of
      the N-terminal nucleophile hydrolase superfamily. The active site Thr-391, the N
      terminal residue of the small subunit, is located in the groove, from which the
      pocket for gamma-glutamyl moiety binding follows. We have further determined the
      structure of the gamma-glutamyl-enzyme intermediate trapped by flash cooling the
      GGT crystal soaked in glutathione solution and the structure of GGT in complex
      with l-glutamate. These structures revealed how the gamma-glutamyl moiety and l
      glutamate are recognized by the enzyme. A water molecule was seen on the carbonyl
      carbon of the gamma-glutamyl-Thr-391 Ogamma bond in the intermediate that is to
      be hydrolyzed. Notably the residues essential for GGT activity (Arg-114, Asp-433,
      Ser-462, and Ser-463 in E. coli GGT) shown by site-directed mutagenesis of human
      GGT are all involved in the binding of the gamma-glutamyl moiety. The structure
      of E. coli GGT presented here, together with sequence alignment of GGTs, may be
      applicable to interpret the biochemical and genetic data of other GGTs.

PMID- 16618937
TI  - Identification of a structural motif crucial for infectivity of hepatitis B
      viruses.
AB  - Infectious entry of hepatitis B viruses (HBV) has nonconventional facets. Here we
      analyzed whether a cell-permeable peptide [translocation motif (TLM)] identified
      within the surface protein of human HBV is a general feature of all
      hepadnaviruses and plays a role in the viral life cycle. Surface proteins of all
      hepadnaviruses contain conserved functional TLMs. Genetic inactivation of the
      duck HBV TLMs does not interfere with viral morphogenesis; however, these mutants
      are noninfectious. TLM mutant viruses bind to cells and are taken up into the
      endosomal compartment, but they cannot escape from endosomes. Processing of
      surface protein by endosomal proteases induces their exposure on the virus
      surface. This unmasking of TLMs mediates translocation of viral particles across
      the endosomal membrane into the cytosol, a prerequisite for productive infection.
      The ability of unmasked TLMs to translocate processed HBV particles across
      cellular membranes was shown by confocal immunofluorescence microscopy and by
      infection of nonpermissive cell lines with HBV processed in vitro with endosomal
      lysate. Based on these data, we propose an infectious entry mechanism unique for
      hepadnaviruses that involves virus internalization by receptor-mediated
      endocytosis followed by processing of surface protein in endosomes. This
      processing activates the function of TLMs that are essential for viral particle
      translocation through the endosomal membrane into the cytosol and productive
      infection.

PMID- 16618938
TI  - Development of bat flight: morphologic and molecular evolution of bat wing
      digits.
AB  - The earliest fossil bats resemble their modern counterparts in possessing greatly
      elongated digits to support the wing membrane, which is an anatomical hallmark of
      powered flight. To quantitatively confirm these similarities, we performed a
      morphometric analysis of wing bones from fossil and modern bats. We found that
      the lengths of the third, fourth, and fifth digits (the primary supportive
      elements of the wing) have remained constant relative to body size over the last
      50 million years. This absence of transitional forms in the fossil record led us
      to look elsewhere to understand bat wing evolution. Investigating embryonic
      development, we found that the digits in bats (Carollia perspicillata) are
      initially similar in size to those of mice (Mus musculus) but that, subsequently,
      bat digits greatly lengthen. The developmental timing of the change in wing digit
      length points to a change in longitudinal cartilage growth, a process that
      depends on the relative proliferation and differentiation of chondrocytes. We
      found that bat forelimb digits exhibit relatively high rates of chondrocyte
      proliferation and differentiation. We show that bone morphogenetic protein 2
      (Bmp2) can stimulate cartilage proliferation and differentiation and increase
      digit length in the bat embryonic forelimb. Also, we show that Bmp2 expression
      and Bmp signaling are increased in bat forelimb embryonic digits relative to
      mouse or bat hind limb digits. Together, our results suggest that an up
      regulation of the Bmp pathway is one of the major factors in the developmental
      elongation of bat forelimb digits, and it is potentially a key mechanism in their
      evolutionary elongation as well.

PMID- 16618940
TI  - Protective role of polyphenols in cyclosporine A-induced nephrotoxicity during
      rat pregnancy.
AB  - The aim of this study was to evaluate the adverse effects of cyclosporine A (CsA)
      toward renal morphogenesis and to test the renoprotective natural antioxidants
      such as provinol (PV). Pregnant rats were divided into four groups. Group I was
      injected SC with olive oil. Group II was treated with oral administration of PV
      and was used as control. Group III animals were injected SC daily with CsA, and
      group IV animals were injected daily with CsA and PV for 21 days of pregnancy.
      Five pups per litter were killed and the kidneys removed and treated by
      morphological and immunohistochemical (IHC) methods. IHC analysis considered two
      proteins responsible for nephrotoxicity in adult rats: inducible nitric oxide
      (iNOS) and matrix metalloproteinase-2 (MMP2). Pregnancy outcomes among CsA
      treated rats demonstrated a reduced number of pups. Pups that were exposed
      antenatally to CsA presented several pathologic findings in all immature
      parenchyma and an increase in iNOS and MMP2 expression. These side effects were
      not observed in kidney of litters born from CsA + PV-treated mothers. Our study
      indicates that CsA induces morphological alterations in renal parenchyma of
      neonates and that PV plays a protective role against these side effects.

PMID- 16618939
TI  - Toward understanding the genetics of alcohol drinking through transcriptome meta
      analysis.
AB  - Much evidence from studies in humans and animals supports the hypothesis that
      alcohol addiction is a complex disease with both hereditary and environmental
      influences. Molecular determinants of excessive alcohol consumption are difficult
      to study in humans. However, several rodent models show a high or low degree of
      alcohol preference, which provides a unique opportunity to approach the molecular
      complexities underlying the genetic predisposition to drink alcohol. Microarray
      analyses of brain gene expression in three selected lines, and six isogenic
      strains of mice known to differ markedly in voluntary alcohol consumption
      provided >4.5 million data points for a meta-analysis. A total of 107 arrays were
      obtained and arranged into six experimental data sets, allowing the
      identification of 3,800 unique genes significantly and consistently changed
      between all models of high or low amounts of alcohol consumption. Several
      functional groups, including mitogen-activated protein kinase signaling and
      transcription regulation pathways, were found to be significantly overrepresented
      and may play an important role in establishing a high level of voluntary alcohol
      drinking in these mouse models. Data from the general meta-analysis was further
      filtered by a congenic strain microarray set, from which cis-regulated candidate
      genes for an alcohol preference quantitative trait locus on chromosome 9 were
      identified: Arhgef12, Carm1, Cryab, Cox5a, Dlat, Fxyd6, Limd1, Nicn1, Nmnat3,
      Pknox2, Rbp1, Sc5d, Scn4b, Tcf12, Vps11, and Zfp291 and four ESTs. The present
      study demonstrates the use of (i) a microarray meta-analysis to analyze a
      behavioral phenotype (in this case, alcohol preference) and (ii) a congenic
      strain for identification of cis regulation.

PMID- 16618941
TI  - Effects of long-term androgen administration on breast tissue of female-to-male
      transsexuals.
AB  - Our aim was to examine the effects of androgen administration on breast tissue
      histology of female-to-male transsexuals and to study the immunohistochemical
      expression of three human tissue kallikreins, hK3 (PSA), hK6, and hK10. We
      studied 23 female-to-male transsexuals who were treated with injectable
      testosterone for 18-24 months. We also used 10 control female breast tissues. All
      tissues were fixed in buffered formalin, embedded in paraffin, and examined by
      hematoxylin-eosin staining and immunohistochemical staining for PSA, hK6, and
      hK10. Females treated with androgens exhibited similar involutionary changes as
      those seen in breast of menopausal women, such as marked reduction of glandular
      tissue, involution of the lobuloalveolar structures, and prominence of fibrous
      connective tissue, but presence of only small amounts of fat tissue. Fibrocystic
      lesions were generally not observed. In immunohistochemistry, in control breast
      tissues, we found moderate to strong cytoplasmic immunoexpression of hK6 and hK10
      in the epithelial ductal and lobuloalveolar structures, but myoepithelial cells
      were negative. Luminal secretions were also positive. In menopausal breast, the
      immunoexpression of hK6 and hK10 was weaker and focal. No control case showed
      immunoexpression for PSA. In female-to-male transsexuals, one case showed focal
      PSA cytoplasmic immunoexpression in the epithelium of moderately involuting
      lobules. Long-term administration of androgens in female-to-male transsexuals
      causes marked reduction of glandular tissue and prominence of fibrous connective
      tissue. These changes are similar to those observed at the end-stage of
      menopausal mammary involution.

PMID- 16618942
TI  - Expression of the DEAD-box/RNA helicase rck/p54 in mouse tissues: implications
      for heterogeneous protein expression.
AB  - rck/p54, a DEAD-box RNA helicase, is closely associated with the basic
      modification of RNA molecules in the process of mRNA transport, RNA decay, and
      translation initiation. In the current study, Western blot analysis revealed that
      rck/p54 protein was ubiquitously expressed in mouse tissues. Interestingly, three
      different-sized rck/p54 proteins were detected by antibodies against mouse
      rck/p54, and these products were differentially expressed in the tissues. An
      immunohistochemical study revealed that rck/p54 was strongly expressed in basal
      cells of the crypt in the gastrointestinal tract and in neuronal bodies of the
      cerebral cortex, and was localized in epithelial cells of the convoluted tubules
      of the kidneys, suggesting that the heterogeneous rck/p54 may play pivotal roles
      in cells committed to become specialized in these tissues.

PMID- 16618943
TI  - Terminal alpha1,4-linked N-acetylglucosamine in Helicobacter pylori-associated
      intestinal metaplasia of the human stomach and gastric carcinoma cell lines.
AB  - Helicobacter pylori (Hp) infection is associated with the development of gastric
      lesions including gastritis, intestinal metaplasia (IM), and gastric carcinoma.
      In humans, Hp is found almost exclusively in the foveolar epithelium of the
      gastric mucosa and rarely colonizes the deeper portions where mucous cells of the
      glands produce mucins with terminal alpha1,4-GlcNAc O-glycans. This structure
      exerts antimicrobial activity against Hp. The development of IM in the stomach is
      characterized by Hp clearance from the metaplastic glands and by major
      alterations in the expression of mucins and mucin-carbohydrates. The present work
      evaluated whether terminal alpha1,4-GlcNAc and sialyl-Tn antigen are implicated
      in the process of Hp clearance from metaplastic glands by analyzing the
      expression of these antigens in different types of IM-complete (n=12) and
      incomplete (n=8)-and in gastric cell lines. Terminal alpha1,4-GlcNAc was not
      detected in IM except in a single foci of one case, indicating that this
      structure is not implicated in the clearance of Hp from IM, in contrast to what
      is observed in normal gastric mucosa. None of the gastric carcinoma cell lines
      studied showed terminal alpha1,4-GlcNAc, suggesting that they do not display a
      gastric gland mucous cell phenotype and therefore are useful models for in vitro
      Hp studies. Finally, sialyl-Tn antigen colocalizes with MUC2 mucin and is present
      in all cases of complete and incomplete IM, suggesting that either or both can be
      implicated in Hp clearance from IM.

PMID- 16618944
TI  - Hematopoietic cells are a source of nidogen-1 and nidogen-2 during mouse liver
      development.
AB  - Nidogen-1 and -2 are key components of basement membranes (BMs). Despite the
      presence of nidogen molecules in the parenchyma of the developing liver, no BMs
      are formed therein. This suggests that, in the liver, nidogens may also have
      functions other than BM formation. As a first step toward the elucidation of the
      possible cell biological functions of nidogens in the developing liver, we aimed
      to study their cellular origin. We localized expression of nidogen-1 and nidogen
      2 on prenatal days 12, 14, and 16 in the developing mouse liver using in situ
      hybridization at the light and electron microscopic level and light microscopic
      immunohistochemistry. Our results show that nidogens are produced both in portal
      anlagen and in the parenchyma during liver development. In the parenchyma,
      transcripts can be found in hepatocytes, precursors of stellate cells,
      endothelial cells and, most interestingly, hematopoietic cells. Using real-time
      PCR, we found that the gene expression for both proteins shows a decrease from
      day 14 to day 16 concomitant with a decrease in the hepatic hematopoiesis. We
      suggest that nidogens may, to some extent, take part in the regulation of hepatic
      hematopoiesis.

PMID- 16618945
TI  - Alemtuzumab as consolidation after a response to fludarabine is effective in
      purging residual disease in patients with chronic lymphocytic leukemia.
AB  - PURPOSE: Treatment with alemtuzumab has resulted in negative responses for
      minimal residual disease (MRD) in patients with chronic lymphocytic leukemia
      (CLL). In a prior analysis we demonstrated that it is possible to achieved MRD
      negativity, as assessed by polyclonality of immunoglobulin heavy chain after
      consolidation with alemtuzumab. This phase II study evaluated 34 patients with
      CLL who received alemtuzumab consolidation in an effort to improve the quality of
      their response to fludarabine-based induction. Subsequent peripheral blood stem
      cell (PBSC) collection and transplantation, tolerability, and pharmacokinetics
      also were assessed. PATIENTS AND METHODS: Thirty-four patients younger than 65
      years who had a clinical response to fludarabine-based induction therapy received
      alemtuzumab 10 mg subcutaneously three times per week for 6 weeks. PBSCs were
      collected after mobilization with cytarabine and granulocyte colony-stimulating
      factor. Blood samples for pharmacokinetics study were taken between days 1 and
      31. RESULTS: The complete response rate improved from 35% after fludarabine
      induction to 79.4% after alemtuzumab consolidation, including 19 patients (56%)
      who achieved MRD negativity. The most common adverse events were injection-site
      reactions and fever. Cytomegalovirus reactivation occurred in 18 patients, all of
      whom were successfully treated with oral ganciclovir. PBSC collection was
      successful in 24 (92%) of 26 patients, and 18 patients underwent autologous PBSC
      transplantation. Alemtuzumab plasma concentrations increased gradually during the
      first 2 weeks and accumulated more rapidly thereafter. CONCLUSION: Subcutaneously
      administered alemtuzumab was effective, safe, and well tolerated as consolidation
      therapy in patients with CLL who responded to fludarabine induction therapy.
      Subsequent PBSCT was feasible thereafter.

PMID- 16618946
TI  - Duration of adjuvant chemotherapy for colon cancer and survival among the
      elderly.
AB  - PURPOSE: In randomized trials, patients with stage III colon cancer who received
      6 months of fluorouracil (FU)-based adjuvant chemotherapy had better survival
      than patients who did not. However, little is known about the predictors of, or
      the survival associated with, duration of chemotherapy in the community. PATIENTS
      AND METHODS: The linked Surveillance, Epidemiology, and End Results-Medicare
      database was used to identify individuals > or = 65 years of age diagnosed with
      stage III colon cancer between 1995 and 1999. We used logistic and Cox
      proportional hazards regression models to analyze factors associated with early
      discontinuation of FU-based chemotherapy among these elderly colon cancer
      patients. RESULTS: Among 1,722 patients who received 1 to 7 months of FU-based
      chemotherapy, older age, being unmarried, and having comorbid conditions were
      associated with receiving less than 5 months of treatment. Among the 1,579
      patients who survived > or = 8 months, the 1,091 (69.1%) who received 5 to 7
      months of treatment had lower overall (hazard ratio [HR], 0.59; 95%, CI 0.49 to
      0.71) and colon cancer-specific (HR, 0.53; 95% CI, 0.43 to 0.66) mortality than
      the 488 (30.9%) who received 1 to 4 months of treatment. CONCLUSION: More than
      30% of elderly patients who initiated FU-based chemotherapy for stage III colon
      cancer and survived for at least 8 months discontinued treatment early. Mortality
      rates among such patients were nearly twice as high as among patients who
      completed 5 to 7 months of treatment. If the association we observed between
      duration of treatment and survival is confirmed, additional investigation is
      warranted to determine whether dose-intensity, cumulative dose, or other factors
      related to receipt of full adjuvant treatment are responsible.

PMID- 16618947
TI  - Study of failure pattern among high-risk breast cancer patients with or without
      postmastectomy radiotherapy in addition to adjuvant systemic therapy: long-term
      results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c
      randomized studies.
AB  - PURPOSE: Postmastectomy radiotherapy (RT) in high-risk breast cancer patients can
      reduce locoregional recurrences (LRRs) and improve disease-free and overall
      survival. The aim of this analysis was to examine the overall disease recurrence
      pattern among patients randomly assigned to receive treatment with or without RT.
      PATIENTS AND METHODS: A long-term follow-up was performed among the 3,083
      patients from the Danish Breast Cancer Cooperative Group 82 b and c trials,
      except in those already recorded with distant metastases (DM) or contralateral
      breast cancer (CBC). The end points were LRR, DM, and CBC, and the follow-up
      continued until DM, CBC, emigration, or death. Information was selected from
      medical records, general practitioners, and the National Causes of Death
      Registry. The median potential follow-up time was 18 years. RESULTS: The 18-year
      probability of any first breast cancer event was 73% and 59% (P < .001) after no
      RT and RT, respectively (relative risk [RR], 0.68; 95% CI, 0.63 to 0.75). The 18
      year probability of LRR (with or without DM) was 49% and 14% (P < .001) after no
      RT and RT, respectively (RR, 0.23; 95% CI, 0.19 to 0.27). The 18-year probability
      of DM subsequent to LRR was 35% and 6% (P < .001) after no RT and RT,
      respectively (RR, 0.15; 95% CI, 0.11 to 0.20), whereas the probability of any DM
      was 64% and 53% (P < .001) after no RT versus RT, respectively (RR, 0.78; 95% CI,
      0.71 to 0.86). CONCLUSION: Postmastectomy RT changes the disease recurrence
      pattern in high-risk breast cancer patients; fewer patients have LRR as first
      site of recurrence, and overall fewer patients have DM.

PMID- 16618948
TI  - Summaries for patients. Does use of screening mammography explain racial and
      ethnic differences in death from breast cancer?

PMID- 16618949
TI  - Summaries for patients. The relationship between green tea intake and type 2
      diabetes in Japanese adults.

PMID- 16618950
TI  - Summaries for patients. Risk for and reduction of pulmonary complications in
      patients undergoing noncardiothoracic surgery: an American College of Physicians
      guideline.

PMID- 16618951
TI  - Does utilization of screening mammography explain racial and ethnic differences
      in breast cancer?
AB  - BACKGROUND: Reasons for persistent differences in breast cancer mortality rates
      among various racial and ethnic groups have been difficult to ascertain.
      OBJECTIVE: To determine reasons for disparities in breast cancer outcomes across
      racial and ethnic groups. DESIGN: Prospective cohort. SETTING: The authors pooled
      data from 7 mammography registries that participate in the National Cancer
      Institute-funded Breast Cancer Surveillance Consortium. Cancer diagnoses were
      ascertained through linkage with pathology databases; Surveillance, Epidemiology,
      and End Results programs; and state tumor registries. PARTICIPANTS: 1,010,515
      women 40 years of age and older who had at least 1 mammogram between 1996 and
      2002; 17,558 of these women had diagnosed breast cancer. MEASUREMENTS: Patterns
      of mammography and the probability of inadequate mammography screening were
      examined. The authors evaluated whether overall and advanced cancer rates were
      similar across racial and ethnic groups and whether these rates were affected by
      the use of mammography. RESULTS: African-American, Hispanic, Asian, and Native
      American women were more likely than white women to have received inadequate
      mammographic screening (relative risk, 1.2 [95% CI, 1.2 to 1.2], 1.3 [CI, 1.2 to
      1.3], 1.4 [CI, 1.3 to 1.4], and 1.2 [CI, 1.1 to 1.2] respectively). African
      American women were more likely than white, Asian, and Native American women to
      have large, advanced-stage, high-grade, and lymph node-positive tumors of the
      breast. The observed differences in advanced cancer rates between African
      American and white women were attenuated or eliminated after the cohort was
      stratified by screening history. Among women who were previously screened at
      intervals of 4 to 41 months, African-American women were no more likely to have
      large, advanced-stage tumors or lymph node involvement than white women with the
      same screening history. African-American women had higher rates of high-grade
      tumors than white women regardless of screening history. The lower rates of
      advanced cancer among Asian and Native American women persisted when the cohort
      was stratified by mammography history. LIMITATIONS: Results are based on a cohort
      of women who had received mammographic evaluations. CONCLUSIONS: African-American
      women are less likely to receive adequate mammographic screening than white
      women, which may explain the higher prevalence of advanced breast tumors among
      African-American women. Tumor characteristics may also contribute to differences
      in cancer outcomes because African-American women have higher-grade tumors than
      white women regardless of screening. These results suggest that adherence to
      recommended mammography screening intervals may reduce breast cancer mortality
      rates.

PMID- 16618952
TI  - The relationship between green tea and total caffeine intake and risk for self
      reported type 2 diabetes among Japanese adults.
AB  - BACKGROUND: In western populations, coffee consumption is associated with a
      reduced risk for type 2 diabetes; however, the effect of green, black, and oolong
      teas is unclear. OBJECTIVE: To examine the relationship between consumption of
      these beverages and risk for diabetes. DESIGN: Retrospective cohort study.
      SETTING: 25 communities across Japan. PARTICIPANTS: A total of 17,413 persons
      (6727 men and 10,686 women; 49% of the original study population) who were 40 to
      65 years of age; had no history of type 2 diabetes, cardiovascular disease, or
      cancer at the baseline lifestyle survey; and completed the 5-year follow-up
      questionnaire. There was no difference in body mass index levels at baseline
      between respondents and nonrespondents. MEASUREMENTS: Questionnaire on
      consumption of coffee; black, green, and oolong teas; and physician-diagnosed
      diabetes. RESULTS: During the 5-year follow-up, there were 444 self-reported new
      cases of diabetes in 231 men and 213 women (5-year event rates, 3.4% and 2.0%,
      respectively). Consumption of green tea and coffee was inversely associated with
      risk for diabetes after adjustment for age, sex, body mass index, and other risk
      factors. Multivariable odds ratios for diabetes among participants who frequently
      drank green tea and coffee (> or =6 cups of green tea per day and > or =3 cups of
      coffee per day) were 0.67 (95% CI, 0.47 to 0.94) and 0.58 (CI, 0.37 to 0.90),
      respectively, compared with those who drank less than 1 cup per week. No
      association was found between consumption of black or oolong teas and the risk
      for diabetes. Total caffeine intake from these beverages was associated with a
      33% reduced risk for diabetes. These inverse associations were more pronounced in
      women and in overweight men. LIMITATIONS: Diabetes was self-reported, no data
      were available on consumption of soda, and the follow-up rate was low.
      CONCLUSIONS: Consumption of green tea, coffee, and total caffeine was associated
      with a reduced risk for type 2 diabetes.

PMID- 16618953
TI  - Telephone care management to improve cancer screening among low-income women: a
      randomized, controlled trial.
AB  - BACKGROUND: Minority and low-income women receive fewer cancer screenings than
      other women. OBJECTIVE: To evaluate the effect of a telephone support
      intervention to increase rates of breast, cervical, and colorectal cancer
      screening among minority and low-income women. DESIGN: Randomized, controlled
      trial conducted between November 2001 and April 2004. SETTING: 11 community and
      migrant health centers in New York City. PATIENTS: 1413 women who were overdue
      for cancer screening. INTERVENTION: Over 18 months, women assigned to the
      intervention group received an average of 4 calls from prevention care managers
      and women assigned to the control group received usual care. Follow-up data were
      available for 99% of women, and 91% of the intervention group received at least 1
      call. MEASUREMENTS: Medical record documentation of mammography, Papanicolaou
      testing, and colorectal cancer screening according to U.S. Preventive Services
      Task Force recommendations. RESULTS: The proportion of women who had mammography
      increased from 0.58 to 0.68 with the intervention and decreased from 0.60 to 0.58
      with usual care; the proportion who had Papanicolaou testing increased from 0.71
      to 0.78 with the intervention and was unchanged with usual care; and the
      proportion who had colorectal screening increased from 0.39 to 0.63 with the
      intervention and from 0.39 to 0.50 with usual care. The difference in the change
      in screening rates between groups was 0.12 for mammography (95% CI, 0.06 to
      0.19), 0.07 for Papanicolaou testing (CI, 0.01 to 0.12), and 0.13 for colorectal
      screening (CI, 0.07 to 0.19). The proportion of women who were up to date for 3
      tests increased from 0.21 to 0.43 with the intervention. LIMITATIONS:
      Participants were from 1 city and had access to a regular source of care. Medical
      records may not have captured all cancer screenings. CONCLUSIONS: Telephone
      support can improve cancer screening rates among women who visit community and
      migrant health centers. The intervention seems to be well suited to health plans,
      large medical groups, and other organizations that seek to increase cancer
      screening rates and to address disparities in care.

PMID- 16618954
TI  - Brief communication: atrial-esophageal fistulas after radiofrequency ablation.
AB  - BACKGROUND: Ablation of atrial fibrillation is generally considered safe and
      effective. However, atrial-esophageal fistulas have recently been reported as a
      rare but fatal complication. OBJECTIVE: To describe 9 patients with atrial
      esophageal fistulas after ablation for atrial fibrillation. DESIGN: Retrospective
      case series. SETTING: Institutions where cardiologists performed atrial
      fibrillation ablation procedures. PATIENTS: 9 patients with atrial-esophageal
      fistulas after atrial fibrillation ablation. MEASUREMENTS: Demographic
      characteristics, mortality, presenting signs and symptoms, and days to
      presentation. RESULTS: Patients presented a mean of 12.3 days (range, 10 to 16
      days) after their procedures. Nonspecific symptoms included fever, leukocytosis,
      and neurologic abnormalities. All patients died. Only 4 patients received correct
      diagnoses before death, although all patients presented to a physician. In 3
      patients, surgical repair was attempted. LIMITATIONS: Few physicians reported
      cases, and only approximate numbers of procedures performed by the physicians are
      known. Thus, the authors could not estimate the incidence of atrial-esophageal
      fistulas after ablation. CONCLUSIONS: Formation of atrial-esophageal fistulas is
      a rare but potentially devastating complication of atrial fibrillation ablation.
      This disorder may have an indolent presentation and may mimic other disease
      states, such as stroke or sepsis.

PMID- 16618955
TI  - Risk assessment for and strategies to reduce perioperative pulmonary
      complications for patients undergoing noncardiothoracic surgery: a guideline from
      the American College of Physicians.
AB  - Postoperative pulmonary complications play an important role in the risk for
      patients undergoing noncardiothoracic surgery. Postoperative pulmonary
      complications are as prevalent as cardiac complications and contribute similarly
      to morbidity, mortality, and length of stay. Pulmonary complications may even be
      more likely than cardiac complications to predict long-term mortality after
      surgery. The purpose of this guideline is to provide guidance to clinicians on
      clinical and laboratory predictors of perioperative pulmonary risk before
      noncardiothoracic surgery. It also evaluates strategies to reduce the
      perioperative pulmonary risk and focuses on atelectasis, pneumonia, and
      respiratory failure. The target audience for this guideline is general internists
      or other clinicians involved in perioperative management of surgical patients.
      The target patient population is all adult persons undergoing noncardiothoracic
      surgery.

PMID- 16618956
TI  - Preoperative pulmonary risk stratification for noncardiothoracic surgery:
      systematic review for the American College of Physicians.
AB  - BACKGROUND: The importance of clinical risk factors for postoperative pulmonary
      complications and the value of preoperative testing to stratify risk are the
      subject of debate. PURPOSE: To systematically review the literature on
      preoperative pulmonary risk stratification before noncardiothoracic surgery. DATA
      SOURCES: MEDLINE search from 1 January 1980 through 30 June 2005 and hand search
      of the bibliographies of retrieved articles. STUDY SELECTION: English-language
      studies that reported the effect of patient- and procedure-related risk factors
      and laboratory predictors on postoperative pulmonary complication rates after
      noncardiothoracic surgery and that met predefined inclusion criteria. DATA
      EXTRACTION: The authors used standardized abstraction instruments to extract data
      on study characteristics, hierarchy of research design, study quality, risk
      factors, and laboratory predictors. DATA SYNTHESIS: The authors determined random
      effects pooled estimate odds ratios and, when appropriate, trim-and-fill
      estimates for patient- and procedure-related risk factors from studies that used
      multivariable analyses. They assigned summary strength of evidence scores for
      each factor. Good evidence supports patient-related risk factors for
      postoperative pulmonary complications, including advanced age, American Society
      of Anesthesiologists class 2 or higher, functional dependence, chronic
      obstructive pulmonary disease, and congestive heart failure. Good evidence
      supports procedure-related risk factors for postoperative pulmonary
      complications, including aortic aneurysm repair, nonresective thoracic surgery,
      abdominal surgery, neurosurgery, emergency surgery, general anesthesia, head and
      neck surgery, vascular surgery, and prolonged surgery. Among laboratory
      predictors, good evidence exists only for serum albumin level less than 30 g/L.
      Insufficient evidence supports preoperative spirometry as a tool to stratify
      risk. LIMITATIONS: For certain risk factors and laboratory predictors, the
      literature provides only unadjusted estimates of risk. Prescreening, variable
      selection algorithms, and publication bias limited reporting of risk factors
      among studies using multivariable analysis. CONCLUSIONS: Selected clinical and
      laboratory factors allow risk stratification for postoperative pulmonary
      complications after noncardiothoracic surgery.

PMID- 16618957
TI  - Strategies to reduce postoperative pulmonary complications after
      noncardiothoracic surgery: systematic review for the American College of
      Physicians.
AB  - BACKGROUND: Postoperative pulmonary complications are as frequent and clinically
      important as cardiac complications in terms of morbidity, mortality, and length
      of stay. However, there has been much less research and no previous systematic
      reviews of the evidence of interventions to prevent pulmonary complications.
      PURPOSE: To systematically review the literature on interventions to prevent
      postoperative pulmonary complications after noncardiothoracic surgery. DATA
      SOURCES: MEDLINE English-language literature search, 1 January 1980 through 30
      June 2005, plus bibliographies of retrieved publications. STUDY SELECTION:
      Randomized, controlled trials (RCTs); systematic reviews; or meta-analyses that
      met predefined inclusion criteria. DATA EXTRACTION: Using standardized forms, the
      authors abstracted data on study methods, quality, intervention and control
      groups, patient characteristics, surgery, postoperative pulmonary complications,
      and adverse events. DATA SYNTHESIS: The authors qualitatively synthesized,
      without meta-analysis, evidence from eligible studies. Good evidence (2
      systematic reviews, 5 additional RCTs) indicates that lung expansion
      interventions (for example, incentive spirometry, deep breathing exercises, and
      continuous positive airway pressure) reduce pulmonary risk. Fair evidence
      suggests that selective, rather than routine, use of nasogastric tubes after
      abdominal surgery (2 meta-analyses) and short-acting rather than long-acting
      intraoperative neuromuscular blocking agents (1 RCT) reduce risk. The evidence is
      conflicting or insufficient for preoperative smoking cessation (1 RCT), epidural
      anesthesia (2 meta-analyses), epidural analgesia (6 RCTs, 1 meta-analysis), and
      laparoscopic (vs. open) operations (1 systematic review, 1 meta-analysis, 2
      additional RCTs), although laparoscopic operations reduce pain and pulmonary
      compromise as measured by spirometry. While malnutrition is associated with
      increased pulmonary risk, routine total enteral or parenteral nutrition does not
      reduce risk (1 meta-analysis, 3 additional RCTs). Enteral formulations designed
      to improve immune status (immunonutrition) may prevent postoperative pneumonia (1
      meta-analysis, 1 additional RCT). LIMITATIONS: The overall quality of the
      literature was fair: Ten of 20 RCTs and 6 of 11 systematic reviews were good
      quality. CONCLUSIONS: Few interventions have been shown to clearly or possibly
      reduce postoperative pulmonary complications.

PMID- 16618958
TI  - Exploring and crossing the disparity divide in cancer mortality.

PMID- 16618959
TI  - Self-management education for osteoarthritis.

PMID- 16618960
TI  - Tamoxifen therapy for retroperitoneal fibrosis.

PMID- 16618961
TI  - Patient counseling and education: should doctors be doing more.

PMID- 16618962
TI  - Analysis of distribution indicates diverse functions of simple sequence repeats
      in Mycoplasma genomes.
AB  - Simple sequence repeats (SSRs) composed of extensive tandem iterations of a
      single nucleotide or a short oligonucleotide are rare in most bacterial genomes,
      but they are common among Mycoplasma. Some of these repeats act as contingency
      loci in association with families of surface antigens. By contraction or
      expansion during replication, these SSRs increase genetic variance of the
      population and facilitate avoidance of the immune response of the host.
      Occurrence and distribution of SSRs are analyzed in complete genomes of 11
      Mycoplasma and 3 related Mollicutes in order to gain insights into functional and
      evolutionary diversity of the SSRs in Mycoplasma. The results revealed an
      unexpected variety of SSRs with respect to their distribution and composition and
      suggest that it is unlikely that all SSRs function as contingency loci or
      recombination hot spots. Various types of SSRs are most abundant in Mycoplasma
      hyopneumoniae, whereas Mycoplasma penetrans, Mycoplasma mobile, and Mycoplasma
      synoviae do not contain unusually long SSRs. Mycoplasma hyopneumoniae and
      Mycoplasma pulmonis feature abundant short adenine and thymine runs periodically
      spaced at 11 and 12 bp, respectively, which likely affect the supercoiling
      propensities of the DNA molecule. Physiological roles of long adenine and thymine
      runs in M. hyopneumoniae appear independent of location upstream or downstream of
      genes, unlike contingency loci that are typically located in protein-coding
      regions or upstream regulatory regions. Comparisons among 3 M. hyopneumoniae
      strains suggest that the adenine and thymine runs are rarely involved in genome
      rearrangements. The results indicate that the SSRs in the Mycoplasma genomes play
      diverse roles, including modulating gene expression as contingency loci,
      facilitating genome rearrangements via recombination, affecting protein structure
      and possibly protein-protein interactions, and contributing to the organization
      of the DNA molecule in the cell.

PMID- 16618963
TI  - Genomic and evolutionary insights into genes encoding proteins with single amino
      acid repeats.
AB  - Mutations causing expansion of amino acid repeats are responsible for 19
      hereditary disorders. Repeats in several other proteins also show length
      variations. These observations prompted us to identify single amino acid repeat
      containing proteins (SARPs) in humans and to understand their functional and
      evolutionary significance. We identified 8812 SARPs containing 17 146 repeat
      domains, each harboring 4 or more residues. In all, 5% of SARPs (471) showed
      repeat length variations, and nearly 84% of them (394) have repeats of 10
      residues or less. We find that SARPs are involved in functions that require
      formation of multiprotein complexes. Nearly 78% (6859) of the SARPs did not find
      a paralogue in the human proteome, and such proteins are considered as orphan
      SARPs. Orphan SARPs show longer repeat stretches, longer peptide length, and
      lower expression levels as compared with SARPs belonging to protein family.
      Because the intensity of gene expression is known to relate inversely with the
      rate of protein sequence evolution, our results suggest that the orphan SARPs
      evolve faster than the familial forms and therefore are under a weaker selection
      pressure. We also find that while GC-rich codons are favored for coding the
      repeat tracts of SARPs, specific codons and not nucleotide motifs per se are
      selected, suggesting functional constraints placed on the usage of codons. One of
      the constraints could be the mRNA stability as clustering of rare codons is known
      to destabilize the transcripts and rare codons are not favored for coding repeat
      tracts. Genes encoding polymorphic SARPs show preferential localization toward
      the telomeric segments. Further, the sex-specific recombination rates of the
      chromosomal locus strongly correlate with the parental gender that influence the
      repeat instability in disorder caused by dynamic mutation. Therefore, instability
      associated with repeats might be driven by processes that are specific to sperm
      or oocyte development, and the recombination frequency might play a positive role
      in this process.

PMID- 16618964
TI  - Archaeology and evolution of transfer RNA genes in the Escherichia coli genome.
AB  - Transfer RNA genes tend to be presented in multiple copies in the genomes of most
      organisms, from bacteria to eukaryotes. The evolution and genomic structure of
      tRNA genes has been a somewhat neglected area of molecular evolution. Escherichia
      coli, the first phylogenetic species for which more than two different strains
      have been sequenced, provides an invaluable framework to study the evolution of
      tRNA genes. In this work, a detailed analysis of the tRNA structure of the
      genomes of Escherichia coli strains K12, CFT073, and O157:H7, Shigella flexneri
      2a 301, and Salmonella typhimurium LT2 was carried out. A phylogenetic analysis
      of these organisms was completed, and an archaeological map depicting the main
      events in the evolution of tRNA genes was drawn. It is shown that duplications,
      deletions, and horizontal gene transfers are the main factors driving tRNA
      evolution in these genomes. On average, 0.64 tRNA insertions/duplications occur
      every million years (Myr) per genome per lineage, while deletions occur at the
      slower rate of 0.30 per million years per genome per lineage. This work provides
      a first genomic glance at the problem of tRNA evolution as a repetitive process,
      and the relationship of this mechanism to genome evolution and codon usage is
      discussed.

PMID- 16618965
TI  - Functional characterization of the conserved amino acids in Pop1p, the largest
      common protein subunit of yeast RNases P and MRP.
AB  - RNase P and RNase MRP are ribonucleoprotein enzymes required for 5'-end
      maturation of precursor tRNAs (pre-tRNAs) and processing of precursor ribosomal
      RNAs, respectively. In yeast, RNase P and MRP holoenzymes have eight protein
      subunits in common, with Pop1p being the largest at >100 kDa. Little is known
      about the functions of Pop1p, beyond the fact that it binds specifically to the
      RNase P RNA subunit, RPR1 RNA. In this study, we refined the previous Pop1
      phylogenetic sequence alignment and found four conserved regions. Highly
      conserved amino acids in yeast Pop1p were mutagenized by randomization and
      conditionally defective mutations were obtained. Effects of the Pop1p mutations
      on pre-tRNA processing, pre-rRNA processing, and stability of the RNA subunits of
      RNase P and MRP were examined. In most cases, functional defects in RNase P and
      RNase MRP in vivo were consistent with assembly defects of the holoenzymes,
      although moderate kinetic defects in RNase P were also observed. Most mutations
      affected both pre-tRNA and pre-rRNA processing, but a few mutations
      preferentially interfered with only RNase P or only RNase MRP. In addition, one
      temperature-sensitive mutation had no effect on either tRNA or rRNA processing,
      consistent with an additional role for RNase P, RNase MRP, or Pop1p in some other
      form. This study shows that the Pop1p subunit plays multiple roles in the
      assembly and function of of RNases P and MRP, and that the functions can be
      differentiated through the mutations in conserved residues.

PMID- 16618966
TI  - Restoration in vivo of defective hepatitis delta virus RNA genomes.
AB  - The 1679-nt single-stranded RNA genome of hepatitis delta virus (HDV) is circular
      in conformation. It is able to fold into an unbranched rodlike structure via
      intramolecular base-pairing. This RNA is replicated by host RNA polymerase II
      (Pol II). Such transcription is unique, because Pol II is known only for its
      ability to act on DNA templates. The present study addressed the ability of the
      HDV RNA replication to tolerate insertions of up to 1000 nt of non-HDV sequence
      either at an end of the rodlike RNA structure or at a site embedded within the
      rod. The insertions did not interfere with the ability of primary transcripts to
      be processed in vivo by ribozyme cleavage and ligation. The insertions greatly
      reduced the ability of genomes to replicate. However, when total RNA from such
      transfected cells was used to transfect new recipient cells, replicating HDV RNAs
      could be detected by Northern analyses. The size of the emerged RNAs was
      consistent with loss of the inserted sequences. RT-PCR, cloning, and sequencing
      showed that recovery involved removal of inserted sequences with or without small
      deletions of adjacent RNA sequences. Such restoration of the RNA genome is
      consistent with a model requiring intramolecular template-switching (RNA
      recombination) during RNA-directed transcription, in combination with biological
      selection for maintenance of the rodlike structure of the template.

PMID- 16618967
TI  - Efficient RNA 5'-adenylation by T4 DNA ligase to facilitate practical
      applications.
AB  - We describe a simple procedure for RNA 5'-adenylation using T4 DNA ligase. The 5'
      monophosphorylated terminus of an RNA substrate is annealed to a complementary
      DNA strand that has a 3'-overhang of 10 nucleotides. Then, T4 DNA ligase and ATP
      are used to synthesize 5'-adenylated RNA (5'-AppRNA), which should find use in a
      variety of practical applications. In the absence of an acceptor nucleic acid
      strand, the two-step T4 DNA ligase mechanism is successfully interrupted after
      the adenylation step, providing 40%-80% yield of 5'-AppRNA after PAGE
      purification with few side products (the yield varies with RNA sequence).
      Optimized reaction conditions are described for 5'-adenylating RNA substrates of
      essentially any length including long and structured RNAs, without need for
      sequestration of the RNA 3'-terminus to avoid circularization. The new procedure
      is applicable on the preparative nanomole scale. This 5'-adenylation strategy
      using T4 DNA ligase is a substantial improvement over our recently reported
      adenylation method that uses T4 RNA ligase, which often leads to substantial
      amounts of side products and requires careful optimization for each RNA
      substrate. Efficient synthetic access to 5'-adenylated RNA will facilitate a
      range of applications by providing substrates for in vitro selection; by
      establishing a new protocol for RNA 5'-capping; and by providing an alternative
      approach for labeling RNA with (32)P or biophysical probes at the 5'-terminus.

PMID- 16618968
TI  - Interactions of mRNAs and gRNAs involved in trypanosome mitochondrial RNA
      editing: structure probing of a gRNA bound to its cognate mRNA.
AB  - Expression of mitochondrial genes in Trypanosoma brucei requires RNA editing of
      its mRNA transcripts. During editing, uridylates are precisely inserted and
      deleted as directed by the gRNA template to create the protein open reading
      frame. This process involves the bimolecular interaction of the gRNA with its
      cognate pre-edited mRNA and the assembly of a protein complex with the enzymatic
      machinery required. While a considerable amount of work has been done identifying
      the protein components of the editing complex, very little is known about how a
      functional editosome is assembled. In addition, the importance of RNA structure
      in establishing a functional editing complex is poorly understood. Work in our
      lab suggests that different mRNA/gRNA pairs can form similar secondary structures
      suggesting that a common core architecture may be important for editosome
      recognition and function. Using solution structure probing, we have investigated
      the structure of the initiating gRNA, gCYb-558, in the mRNA/gRNA complex with pre
      edited apocytochrome b mRNA. Our data indicate that the stem-loop formed by the
      guiding region of the gRNA alone is maintained in its interaction with the pre
      edited message. In addition, our data suggest that a gRNA stem-loop structure is
      maintained through the first few editing events by the use of alternative base
      pairing with the U-tail.

PMID- 16618969
TI  - Residues in two homology blocks on the amino side of the tRNase Z His domain
      contribute unexpectedly to pre-tRNA 3' end processing.
AB  - tRNase Z, which can endonucleolytically remove pre-tRNA 3'-end trailers,
      possesses the signature His domain (HxHxDH; Motif II) of the beta-lactamase
      family of metal-dependent hydrolases. Motif II combines with Motifs III-V on its
      carboxy side to coordinate two divalent metal ions, constituting the catalytic
      core. The PxKxRN loop and Motif I on the amino side of Motif II have been
      suggested to modulate tRNase Z activity, including the anti-determinant effect of
      CCA in mature tRNA. Ala walks through these two homology blocks reveal residues
      in which the substitutions unexpectedly reduce catalytic efficiency. While
      substitutions in Motif II can drastically affect k(cat) without affecting k(M),
      five- to 15-fold increases in k(M) are observed with substitutions in several
      conserved residues in the PxKxRN loop and Motif I. These increases in k(M)
      suggest a model for substrate binding. Expressed tRNase Z processes mature tRNA
      with CCA at the 3' end approximately 80 times less efficiently than a pre-tRNA
      possessing natural sequence of the 3'-end trailer, due to reduced k(cat) with no
      effect on k(M), showing the CCA anti-determinant to be a characteristic of this
      enzyme.

PMID- 16618970
TI  - Arrested yeast splicing complexes indicate stepwise snRNP recruitment during in
      vivo spliceosome assembly.
AB  - Pre-mRNA splicing is catalyzed by the spliceosome, a macromolecular machine
      dedicated to intron removal and exon ligation. Despite an abundance of in vitro
      information and a small number of in vivo studies, the pathway of yeast
      (Saccharomyces cerevisiae) in vivo spliceosome assembly remains uncertain. To
      address this situation, we combined in vivo depletions of U1, U2, or U5 snRNAs
      with chromatin immunoprecipitation (ChIP) analysis of other splicing snRNPs along
      an intron-containing gene. The data indicate that snRNP recruitment to nascent
      pre-mRNA predominantly proceeds via the canonical three-step assembly pathway:
      first U1, then U2, and finally the U4/U6*U5 tri-snRNP. Tandem affinity
      purification (TAP) using a U2 snRNP-tagged protein allowed the characterization
      of in vivo assembled higher-order splicing complexes. Consistent with an
      independent snRNP assembly pathway, we observed high levels of U1-U2
      prespliceosomes under U5-depletion conditions, and we observed significant levels
      of a U2/U5/U6/Prp19-complex mature splicing complex under wild-type conditions.
      These complexes have implications for the steady-state distribution of snRNPs
      within nuclei and also reinforce the stepwise recruitment of U1, U2, and the tri
      snRNP during in vivo spliceosome assembly.

PMID- 16618972
TI  - Split centromeric alpha-satellite FISH signals in a whole arm translocation
      5p;10p: consequences and implications for interphase FISH studies.
AB  - This is a case report of an apparently balanced whole arm translocation between
      the short arms of chromosomes 5 and 10 in which the centromeric alpha-satellite
      DNA is split between both derivative chromosomes for both probes, leading to
      abnormal signal patterns. The patient requested preimplantation genetic testing
      for the unbalanced products of the translocation. However, using centromeric
      alpha-satellite DNA probes as controls for the subtelomeric-specific probes in
      interphase was not informative because of the split signals. The ramifications of
      such variation in the alpha-satellite regions of chromosomes for other interphase
      FISH tests are discussed.

PMID- 16618971
TI  - Autoregulation of the mRNA export factor Yra1p requires inefficient splicing of
      its pre-mRNA.
AB  - Yra1p is an essential RNA-binding protein that couples transcription to export.
      The YRA1 gene is one of only approximately 5% of genes that undergo splicing in
      budding yeast, and its intron is unusual in several respects, including its large
      size and anomalous branchpoint sequence. We showed previously that the intron is
      required for autogenous regulation of Yra1p levels, which cause a dominant
      negative growth phenotype when elevated. The mechanism of this regulation,
      however, remains unknown. Here we demonstrate that growth is inversely correlated
      with splicing efficiency. Substitution of a canonical branchpoint moderately
      improves splicing but compromises autoregulation. Shortening the intron from 766
      to approximately 350 nt significantly improves splicing but abolishes
      autoregulation. Notably, proper regulation can be restored by insertion of
      unrelated sequences into the shortened intron. In that the current paradigm for
      regulated splicing involves the binding of protein factors to specific elements
      in the pre-mRNA, the regulation of YRA1 expression appears to occur by a novel
      mechanism. We propose that appropriate levels of Yra1p are maintained by
      inefficient cotranscriptional splicing.

PMID- 16618973
TI  - Nuclear receptor mediated gene regulation through chromatin remodeling and
      histone modifications.
AB  - Nuclear steroid/thyroid vitamin A/D receptor genes form a gene superfamily and
      encode DNA-binding transcription factors that control the transcription of target
      genes in a ligand-dependent manner. It has become clear that chromatin remodeling
      and the modification of histones, the main components of chromatin, play crucial
      roles in gene transcription, and many distinct classes of NR-interacting co
      regulators have been identified that perform significant roles in gene
      transcription. Since NR dysfunction can lead to the onset or progression of
      endocrine disease, elucidation of the mechanisms of gene regulation mediated by
      NRs, as well as the identification and characterization of co-regulator complexes
      (especially chromatin remodeling and histone-modifying complexes), is essential
      not only for better understanding of NR ligand function, but also for
      pathophysiological studies and the development of therapeutic interventions in
      humans.

PMID- 16618974
TI  - Development of cookie test for the simultaneous determination of glucose
      intolerance, hyperinsulinemia, insulin resistance and postprandial dyslipidemia.
AB  - A new cookie test was developed for the simultaneous evaluation of multiple risk
      factors such as glucose intolerance, hyperinsulinemia, insulin resistance and
      postprandial dyslipidemia. The cookie consisting of 75 g carbohydrate and 25 g
      fat is ingested and the blood samples are obtained at 0, 1 and 2 hours later.
      When the two carbohydrate sources, liquid glucose and test cookie, were compared
      as a glucose load within 3 months, the 2 hr plasma glucose levels were not
      statistically different, proposing the use of the same criteria at 2 hour glucose
      level for the diagnosis of diabetes and impaired glucose tolerance (IGT) in
      subjects without exocrine pancreatic dysfunction. In addition, hyperinsulinemia,
      insulin resistance (AUC insulin, and/or AUC insulin X AUC glucose), and
      postprandial hyperlipidemia (DeltaTG, Triglyceride; DeltaRLP, remnant like
      particles) have been simultaneously uncovered. Reactive hypoglycemia with adverse
      epigastric discomfort was observed in 26.3% of the control subjects with liquid
      glucose, while it was observed in only 1 case (5.3%) without any symptom with
      cookie tests. In fact, one reactive hypoglycemia out of 5 with liquid glucose
      turned out to be IGT with cookie test. In 64 subjects with lifestyle-related
      diseases, cookie test revealed hyperinsulinemia and insulin resistance in 56%
      respectively, postprandial hyperlipidemia in 39%, diabetes and IGT in 22-23% of
      each of the subjects and all showed at least one abnormal value. In contrast, in
      university students with exercise habit, all showed normal results with cookie
      test. In addition, improved insulin sensitivity over non-exercise group was
      obverved. In summary, the cookie test provided more informations compared with
      OGTT using liquid glucose and with fewer side effects. Simultaneous evaluation of
      glucose intolerance, hyperinsulinemia, insulin resistance, and postprandial
      hyperlipidemia was also possible.

PMID- 16618975
TI  - Expression of thyroid hormone receptor isoforms down-regulated by thyroid hormone
      in human medulloblastoma cells.
AB  - The role of thyroid hormone (T3) in the regulation of growth and development of
      the central nervous system including the cerebellum has been well established.
      However, the effects of thyroid hormone on malignant tumors derived from the
      cerebellum remain poorly understood. Our analysis mainly focused on expression
      levels of TR isoforms and the effects of thyroid hormone in human medulloblastoma
      HTB-185 cells. Northern blot analysis revealed TRalpha2 mRNA but not TRalpha1,
      beta1 or beta2 mRNA in the cell. The TRalpha1 and TRbeta1 mRNAs were detected
      only by RT-PCR method and TRbeta2 was not expressed. Incubation of T3 for 24 h
      decreased TRalpha1, TRalpha2 and TRbeta1 mRNA. Addition of actinomycin D caused
      an acute increase in the basal TR mRNA levels and the rate of decrease of all
      kinds of TR isoform mRNA was accelerated in the T3-treated groups compared to
      controls, indicating that the stability of TR mRNA was affected by T3. Incubation
      with cycloheximide also blocked a decrease in TR mRNA levels in the T3-treated
      HTB-185 cells suggesting that down-regulation of TR mRNA required the synthesis
      of new protein. Our data provide novel evidence for the expression of TRs down
      regulated by T3 in HTB-185 cells, suggesting that TR expression is post
      transcriptionally regulated by T3 at the level of RNA stability.

PMID- 16618976
TI  - Effect of exercise on circulating adipokine levels in obese young women.
AB  - We studied the effect of exercise on circulating adipokine, high sensitivity C
      reactive protein (hs-CRP), and metabolic parameters in obese young women. Ninety
      six healthy Japanese young female students aged 18-23 years were studied. The
      longitudinal intervention study of a 7-month exercise training program (30-60
      min/day, 60-70% HR-reserve, 200-400 kcal, 4-5 days/week) was performed in eight
      obese female students (BMI > or =25 kg/m(2)). Eight control female students (mean
      BMI = 22 kg/m(2)) were included in the follow-up study. Body weight, body mass
      index (BMI), percentage of body fat (%Fat), body fat mass, lean body mass, health
      promoting lifestyle profile-scale (L-scale), VO(2)max (maximal oxygen uptake), hs
      CRP, lipids, insulin homeostasis model assessment (HOMA-R), fasting levels for
      circulating adiponectin, leptin, and TNF-alpha, were measured before and after
      the exercise program. In obese subjects, body weight, BMI, %Fat, body fat mass,
      lean body mass, hs-CRP, leptin, and TNF-alpha were significantly higher, and L
      scale and adiponectin were lower than those in control subjects. In obese
      subjects, exercise decreased body weight, BMI, %Fat, body fat mass, lean body
      mass, hs-CRP, leptin, and TNF-alpha, and increased L-scale, VO(2)max, HDL-cho,
      and adiponectin. It was concluded that changes in circulating adipokine levels
      are involved in the improvement of the metabolic state by exercise and may be
      useful markers for evaluation and prescription of exercise.

PMID- 16618977
TI  - Thrombospondin 1 mRNA as a candidate for a marker to detect thyroid-derived
      fibroblasts in fine needle aspiration biopsy of the thyroid.
AB  - Possible interference of fibroblasts is suggested in aspiration biopsy nucleic
      acid diagnosis (ABND). However, detection of fibroblasts in the aspirates is
      difficult, because the gene expression profiles of thyroid malignancies and
      fibroblasts are much alike in many aspects. To identify a specific marker for
      thyroid-derived fibroblasts, the data of the serial analysis of gene expression
      (SAGE) were compared to screen differentially expressed genes between fibroblasts
      and thyroid normal and tumor tissues. In the SAGE data, 5 genes were identified
      to be differentially expressed. Among these, thrombospondin 1 (TSP-1, THBS1) mRNA
      was the most differentially expressed. Further, the overexpression of TSP-1 mRNA
      in fibroblasts was confirmed by real-time RT-PCR analysis using 73 thyroid normal
      and tumor tissues and 7 cultures of thyroid-derived fibroblasts. These results
      suggest that TSP-1 mRNA is a possible marker for contamination of thyroid-derived
      fibroblasts.

PMID- 16618978
TI  - Reduction of a pancreatic tumor after total removal of an ACTH secreting
      pituitary tumor: differential diagnosis of Cushing's syndrome.
AB  - Endocrinologic tests sometimes fail to distinguish adrenocorticotropic hormone
      (ACTH)-secreting pituitary adenoma from ectopic ACTH-secreting tumor. The authors
      experienced a case of Cushing's disease associated with a pancreatic tumor.
      Venous sampling contributed to the final diagnosis of Cushing's disease in this
      complex case, while endocrinologic tests showed paradoxical results. A 54-year
      old woman presented with Cushing's syndrome and pancreatic tumor. Magnetic
      resonance imaging (MRI) failed to reveal a pituitary tumor, but a gadolinium
      enhanced tumor with cystic components was seen in the pancreatic tail. Results of
      conventional endocrinologic tests suggested ectopic ACTH syndrome, but venous
      sampling including cavernous sinus sampling indicated an ACTH-secreting pituitary
      adenoma. Transsphenoidal surgery revealed a pituitary microadenoma, and total
      removal of the tumor was achieved. Postoperative abdominal MRI revealed that the
      pancreatic tumor diminished gradually without treatment. Selective cavernous
      sinus sampling was useful for distinguishing ACTH-secreting pituitary adenoma
      from ectopic ACTH syndrome in this complex case. This was a rare case in which
      the pancreatic tumor diminished after total removal of the ACTH-secreting
      pituitary adenoma.

PMID- 16618979
TI  - Normal delivery following an uneventful pregnancy in a Japanese acromegalic
      patient after discontinuation of octreotide long acting release formulation at an
      early phase of pregnancy.
AB  - We report a 35-year-old woman with active acromegaly despite pituitary surgery
      and irradiation who received continuous octreotide LAR treatment for the control
      of GH excess until discovery of her pregnancy. The patient delivered a healthy
      boy following an uneventful pregnancy after discontinuing octreotide LAR as soon
      as possible at the early phase of pregnancy. Despite a substantial maternal-fetal
      transfer of octreotide, postnatal development was normal at 3 years of age. In
      almost all previously described cases, octreotide was discontinued after
      pregnancy was confirmed. No side-effects of mother or fetus have been reported.
      Octreotide treatment in pregnancy seems to be feasible and safe. Due to the still
      limited number of reported cases treated with octreotide LAR, the potential
      benefits of octreotide LAR treatment should be weighed carefully against its
      possible risks.

PMID- 16618980
TI  - Efficacy and adverse effects of nateglinide in early type 2 diabetes. Comparison
      with voglibose in a cross-over study.
AB  - An open-label prospective cross-over trial was performed to compare the efficacy
      and adverse effects of nateglinide with those of voglibose on Japanese early type
      2 diabetes (who were oral hypoglycemic agent naive and whose HbA(1C) levels were
      between 7.0 and 7.9% before treatment). Fourteen patients received 270 mg/day of
      nateglinide and 15 patients received 0.6 mg/day of voglibose. After 12 weeks of
      either therapy, the drugs were switched and treatment was continued for another
      12 weeks. After 3-month treatment with each drug, HbA(1C) value decreased
      significantly (baseline HbA(1C) 7.24 +/- 0.42%, 6.70 +/- 0.47% with nateglinide:
      p<0.01, 6.93 +/- 0.62% with voglibose: p<0.05) but the difference in the effect
      between nateglinide and voglibose was not significant (p = 0.121). Symptoms
      related to hypoglycemia (e.g., increased appetite, palpitation, sweating, tremor)
      were scarcely observed with either voglibose or nateglinide treatments. Abdominal
      fullness/borborygmi was frequently reported, with variable severity, by patients
      on voglibose but this was absent or mild in those on nateglinide. After
      completion of both arms of the study, more patients favored nateglinide than
      voglibose. Our results suggest that nateglinide is an effective and safe drug in
      the treatment of early type 2 diabetes, similar to voglibose.

PMID- 16618981
TI  - Adrenal tuberculosis in Cushing's disease with bilateral macronodular
      adrenocortical hyperplasia.
AB  - Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro-
      or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal
      enlargement, which depends on the duration of the disease, as a result of the
      long standing ACTH stimulation of both adrenal glands. However, in macronodular
      adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH
      gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary
      adenoma, is often essential. We encountered a patient diagnosed with Cushing's
      disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti
      tuberculosis medications one year prior to admission due to spinal tuberculosis.
      Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement
      in both adrenal glands that appeared to be MNH. A hormonal study and bilateral
      inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she
      underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery
      was successful and the serum cortisol returned to normal range. However, the
      adrenal mass rapidly enlarged after removing the pituitary tumor without showing
      evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a
      laparoscopic left adrenalectomy was performed to examine the nature of the mass.
      The resected left adrenal gland was pathologically determined to have a lesion of
      tuberculosis with some part of the intact cortex. So we assumed that the cause of
      rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to
      the best of our knowledge, this is the first case of Cushing's disease coexisting
      with both adrenal tuberculosis simulating a bilateral MNH.

PMID- 16618982
TI  - Activation of follistatin promoter by GnRH in LbetaT2 gonadotroph cells.
AB  - Follistatin (FS) is produced and secreted from gonadotroph cells in pituitary
      gland as well as granulosa cells in the ovary. In the present study, we found
      that the FS promoter is activated by GnRH in the gonadotroph cell line, LbetaT2.
      Therefore, we examined the signal transduction pathways involved in the
      mechanism. The activation of the FS promoter by GnRH was inhibited by calphostin
      C, a protein kinase C inhibitor, and U0126, a MAP kinase kinase (MEK) inhibitor.
      Phosphorylation by protein kinase C of myristoylated alanine-rich C kinase
      substrate (MARCKS) in LbetaT2 cells was observed after 3-min treatment with GnRH
      and declined after 30 min. The subsequent activation of MAP kinase was also
      transient, and down-regulation of protein kinase C completely inhibited the MAP
      kinase activation by GnRH, suggesting that the transient activation of protein
      kinase C led to the transient activation of MAP kinase. Although phorbol 12
      myristate 13-acetate treatment increased phosphorylation of MARCKS and activated
      MAP kinase, it did not activate the FS promoter. Genistein, a tyrosine kinase
      inhibitor, completely inhibited the GnRH-induced activation of the FS promoter,
      while no inhibition of the MAP kinase pathway was observed. These results suggest
      that the activations of both the protein kinase C and tyrosine kinase pathways
      are necessary for the activation of the FS promoter in gonadotroph cells.

PMID- 16618983
TI  - A case of estrogen-secreting adrenocortical carcinoma with subclinical Cushing's
      syndrome.
AB  - A 25-year-old man was found to have a large right adrenal mass detected by
      abdominal echography and computed tomography, and presented with a mild
      gynecomastia. Endocrine study showed increased serum concentrations and urinary
      excretion of estrogens and dehydroepiandorosterone sulfate (DHEA-S). The patient
      had no Cushingoid features but autonomous cortisol secretion, compatible with the
      diagnosis of subclinical Cushing's syndrome. Surgical removal of the adrenal
      tumor led to normalization of serum and urinary excretion of estrogens and DHEA
      S. Histopathological examination revealed a high-grade adrenocortical carcinoma
      (ACC). The disorganized expression of all the steroidogenic enzymes in individual
      tumor cells was demonstrated by immunohistochemical analysis, and the abundant
      expression of both aromatase mRNA and insulin-like growth factor (IGF)-II mRNA
      was shown by RT-PCR. These data suggest the excessive secretion of estrogen as
      well as the ineffective steroidogenesis by the adrenal tumor. This is a very rare
      case of estrogen-secreting ACC associated with subclinical Cushing's syndrome.

PMID- 16618984
TI  - Relationship between plasma adiponectin levels and the metabolic syndrome among
      Korean people.
AB  - We investigated the relationship between plasma adiponectin levels and the
      parameters of the metabolic syndrome among Koreans. In 67 male and 115 female
      subjects, aged from 30 to 70 years, plasma adiponectin levels were positively
      correlated with HDL-cholesterol levels (r = 0.295, P<0.001), but negatively
      correlated with waist circumference (r = -0.140, P = 0.020), triglycerides (r = 
      0.174, P = 0.021), fasting plasma glucose (r = -0.159, P = 0.036), fasting plasma
      insulin (r = -0.172, P = 0.023) and HOMA-IR (r = -0.182, P<0.001), after
      adjustment for age, sex, and BMI. Stepwise multiple regression analyses revealed
      that HDL-cholesterol, sex, and HOMA-IR were the independent associated factors
      for plasma adiponectin levels. Multiple logistic analyses demonstrated that HOMA
      IR, BMI, and age were the predominant independent factors associated with the
      metabolic syndrome, while plasma adiponectin levels exhibited a protective effect
      against the presence of the metabolic syndrome according to both NCEP ATP III
      criteria and IDF definition. Hypoadiponectinemia is associated with the phenotype
      of the metabolic syndrome as well as components of the metabolic syndrome.

PMID- 16618985
TI  - Acute onset of steroid psychosis with very low dose of prednisolone in Sheehan's
      syndrome.
AB  - Corticosteroid treatment is frequently associated with psychiatric disturbances.
      These adverse effects are unusual with low dose of corticosteroid. We describe a
      patient who rapidly developed a steroid-induced psychosis with very low dose of
      prednisolone. A 48-year-old woman of Sheehan's syndrome was admitted to hospital
      with insomnia, euphoric moods and visual hallucinations. She had taken
      prednisolone (10 mg in the morning and 5 mg at night) for 6 days before
      admission. These symptoms appeared after first dose of prednisolone. A diagnosis
      of acute psychosis was made. After improvement of acute psychosis with
      discontinuation, re-administration of prednisolone at a dose of 2.5 mg per day
      gave rise to agitation and insomnia. She recovered completely by gradual dosage
      increase of short-acting corticosteroid after the discontinuation of
      prednisolone.

PMID- 16618987
TI  - [Catalase: structure, properties, functions].
AB  - Catalase (EC 1.11.1.6) is an enzyme which is present mainly in the peroxisomes of
      mammalian cells. It is a tetrameric enzyme consisting of four identical,
      tetrahedrally arranged subunits of 60 kDa, each containing in its active center a
      heme group and NADPH. Catalase has two enzymatic activities depending on the
      concentration of H2O2. If the concentration of H2O2 is high, catalase acts
      catalytically, i.e. removes H2O2 by forming H2O and O2 (catalatic reaction).
      However, at a low concentration of H2O2 and in the presence of a suitable
      hydrogen donor, e.g. ethanol, methanol, phenol, and others, catalase acts
      peroxidically, removing H2O2, but oxidizing its substrate (peroxidatic reaction).
      The review article presents current knowledge about the structure, properties,
      and functions of catalase in living organisms.

PMID- 16618986
TI  - Clinical characteristics, etiologies and pathophysiology of patients with severe
      short stature with severe GH deficiency: questionnaire study on the data
      registered with the foundation for growth science, Japan.
AB  - In this study, we sent questionnaires to doctors treating severe short stature
      with severe GH deficiency (GHD) (height SDS (HtSDS) below -4 and all peak GH to
      provocative stimuli below 2 micro/L) (abbreviated as Severe Case), and obtained
      effective replies of 51 cases. The clinical characteristics, etiologies, and
      pathophysiology of these patients were examined. Among the 51 Severe Cases no
      consanguinity was observed, 44 were IGHD (24 males and 20 females), 3 were GH-1
      gene deletion, 2 were Pit-1 gene mutation, and 2 were achondroplasia. HtSDS in
      these Severe Cases was already remarkably low at 12 (-3.0) and 24 months old (
      3.9), while their birth weight and birth length were within normal ranges. Among
      44 patients with IGHD, 12 were isolated GHD, and the remaining 32 were combined
      pituitary hormone deficiency (CPHD). Pituitary MRI was undergone in 25 idiopathic
      GHD, and abnormal findings (pituitary atrophy, interruption of stalk, and ectopic
      posterior lobe) were observed in 21 patients with CPHD. More than half of these
      patients had the history of breech delivery. Three patients with GH-1 gene
      mutation showed normal pituitary MRI, whereas one of two patients with Pit-1
      mutation showed pituitary atrophy and narrowing of pituitary stalk. In
      conclusion, Severe Cases tended to have CPHD, and the incidence of Severe Case
      was only 0.6% of total IGHD. Although GHD due to genetic disorders is considered
      to be extremely rare (0.06% of total IGHD), the incidence reaches high levels
      (9.8%) among Severe Cases. Growth disorders in these Severe Cases seem to occur
      soon after delivery. Much earlier diagnosis and hGH treatment are desirable to
      attain better final height in the Severe Cases. GH-1 and Pit-1 gene analyses are
      crucial, when genetic abnormalities other than achondroplasia are suspected.

PMID- 16618988
TI  - Lung cancer as an immune reconstitution disease in an HIV-1 positive man
      receiving HAART.
AB  - A case of small-cell lung cancer with prompt worsening of the clinical course was
      observed in a patient with significant immune restoration after receiving
      effective highly active antiretroviral therapy (HAART) for seven months. Rapid
      and enormous enlargement of metastatic liver was the main symptom. Chest x-ray
      showed an enlargement of the left hilus. The patient died 22 days after the onset
      of the fulminant disease. We suggest that the occurrence and aggressive course of
      the lung cancer resulted from the development of immune reconstitution syndrome.

PMID- 16618989
TI  - [The metabolism of glycosaminoglycans in the course of Graves' disease].
AB  - Glycosaminoglycans (GAGs), which include chondroitin sulfate (CS), dermatan
      sulfates (DS), heparan sulfate (HS), heparin (H), keratan sulfate (KS), and
      hyaluronic acid (HA), are a group of linear, polyanionic heteropolysaccharides.
      The GAGs chains, except for those of hyaluronic acid, are covalently attached to
      core proteins, forming proteoglycans (PGs). PGs/GAGs are present at the cellular
      level as elements of the cell membrane and intracellular granules. They are also
      components of the ground substance of the extracellular matrix. These
      macromolecules are involved in cell adhesion, migration, and proliferation.
      Alterations in GAGs metabolism may influence the pathogenesis of many disorders,
      including Graves' disease. Graves' disease is an autoimmune thyroid pathology
      characterized by hyperthyroidism, thyroid hyperplasia, as well as ophthalmopathy
      and/or pretibial myxedema. The pathogenesis of these extrathyroidal
      manifestations involves fibroblast activation and increased glycosaminoglycan
      synthesis and accumulation. Disturbances in GAGs metabolism in tissue are
      associated with qualitative and quantitative GAGs alterations in Graves'
      patients' serum and urine. Although the mechanisms leading to the development of
      orbital and/or skin complications in the course of Graves' disease have not been
      fully elucidated, it is postulated that they depend on both immunological
      disturbances and the hyperthyroid state. SUMMARY: The alterations in GAGs
      metabolism connected with Graves' disease could lead to systemic changes in the
      proprieties of the extracellular matrix.

PMID- 16618990
TI  - [Immunological aspects of trauma].
AB  - Injury breaks anatomical barriers of the body and leads to cell and tissue
      destruction. In response to trauma, repair and defense mechanisms, involved in
      tissue repair, wound healing, and prevention of infection, are induced. The
      magnitude of the trauma-induced response depends on the patient's overall
      condition and the severity of the injury. Minor injury usually elicits a local
      reaction, while severe trauma is associated with a systemic host response. In any
      case, the character of the response is very complex and involves the activation
      of crucial systems: (immunological, neural, and endocrine. The influence of
      different types of injury on immune response has been of interest to scientists
      for many years. Several studies have shown disturbances in innate and adaptive
      immune response as a consequence of burns, accident trauma, and surgical
      operation. It is generally accepted that major surgery often leads to severe
      immunosuppression, usually lasting for several days after injury and
      characterized by impaired cell-mediated immune response. Both clinical and
      experimental studies have demonstrated that one of the main causes of surgery
      induced suppression of cellular immunity might be a shift in the T helper 1
      TH1/TH2 pattern and type-1/type-2 cytokine secretion towards a TH2 response. The
      type and extent of the body's immune response to injury depends not only on
      functional changes of immune cells. An appropriate distribution of immune cells
      among different tissues and organs of the body is also required for proper
      function of the immune system.

PMID- 16618991
TI  - [Control of over-activated innate immunity].
AB  - The basic reactions of innate immunity are reviewed. The mechanisms of innate
      immunity described are: phagocytosis, secretion and activity of cytokines,
      cytokine-dependent resistance of leukocytes to viral infections, the killing
      activity of NK cells independent on MHC, and killing by lectin-activated
      complement. Properly controlled, these mechanisms are responsible for maintaining
      homeostasis. Deficiency is frequently associated with the occurrence of
      infections or tumor diseases. On the other hand, over-activation is observed in
      autoimmunity, neurodegeneration, and inflammatory diseases. It is usually
      accompanied by elevated cytokine production, NO, oxidative stress, and the
      killing of cells. Therefore, the mechanisms which control the reactions of
      natural immunity are of importance for human and animal organisms. Natural
      mechanisms in human and animal organisms which mitigate these reactions are know.
      Among the mechanisms controlling innate immunity are cytokines (IL-10, TGFbeta),
      suppressors of cytokines signaling (SOCS), Tyro-3 receptors, and adenosine and
      adenosine phosphates. The possible participation of other mechanisms involved in
      controlling innate immunity are also considered.

PMID- 16618992
TI  - Surface roughness of three resin restorative materials after finishing and
      polishing.
AB  - AIM: The surface roughness of 3 different resin restorative materials polymerized
      with a halogen and a plasma arc curing light, following finishing and polishing
      was evaluated in vitro. METHODS: Using a metal mold, 10 block specimens were
      prepared from each material. A Mylar strip was placed on both sides of the mold.
      Five specimens from each material were cured with the halogen lamp, while the
      other 5 were polymerized with the plasma arc lamp. In both groups the surface
      exposed to curing light was finished and polished with the Enhance system
      (Dentsply). The opposite surface was not treated and served as a control. Both
      surfaces of each specimen were analyzed with a laser profilometer: the roughness
      average (R(a)) was evaluated. The Vickers microhardness of the polished surfaces
      was also calculated. All data were statistically analyzed with the Mann-Whitney
      test. A regression test was carried out to evaluate the possible correlation
      between roughness and microhardness. RESULTS: The smoothest surfaces were
      obtained when composites were cured against a Mylar strip. Roughness was
      significantly increased in both groups in the treated surfaces. A significant
      correlation between roughness and microhardness could not be demonstrated.
      CONCLUSIONS: This study demonstrated that the surface polymerized against a Mylar
      strip was the smoothest surface produced, while the roughness of the Mylar-formed
      surface was significantly increased by finishing and polishing. Surface roughness
      following polishing is material-dependent.

PMID- 16618993
TI  - Histomorphometric evaluation of bone grafts harvested by different methods.
AB  - AIM: Many studies proposing the use of autologous bone to correct bony defects of
      the oral district have been published, and numerous protocols have been proposed
      to simplify the harvesting of particulate bone. However, no qualitative
      evaluation of the harvested bone has been reported. The study provides a
      qualitative evaluation of autologous bone harvested by 9 methods: the harvested
      bone was analysed through microphotography and histomorphometric analysis,
      measuring the surface area of bone fragments and the percentages of vital and
      necrotic bone. METHODS: Nine harvesting methods were employed: round bur on low
      speed hand-piece (40000 rpm), bur on high-speed hand-piece, spiral implant bur on
      low-speed hand-piece (1000 rpm), safe scraper, Rhodes' back-action chisel,
      rongeur pliers, gouge shaped bone chisel, mectron piezosurgery. Ten bone harvests
      were taken from the retromolar bone using the 9 methods, during extraction of
      embedded wisdom teeth (indication to extraction was for orthodontic reasons). The
      histocytological preparations were analysed with microphotography and
      histomorphometric analysis, evaluating particle size, percentage of vital bone
      and number of osteocytes per unit of surface area. RESULTS: Histomorphometric
      analysis showed that non-vital bone accounted for 100% of harvested bone, with a
      complete absence of osteocytes, in specimens harvested with burs and safe
      scraper. Percentage of non-vital bone was intermediate, with a low number of
      cells, in specimens harvested with back-action, gouge shaped bone chisel, spiral
      bur and piezosurgery. The best results were achieved with rongeur pliers and by
      en bloc harvesting. CONCLUSIONS: The results show that the best methods to
      harvest vital bone are: gouge shaped bone chisel, back-action, en bloc
      harvesting, rongeur pliers and piezosurgery, although the latter method leaves
      some empty gaps in the tissue. The bone harvested with round bur on low-speed
      hand-piece, bur on high-speed hand-piece, spiral implant bur, or safe scraper are
      not suitable for grafting as indicated by the absence of osteocytes and the
      predominance of non-vital bone.

PMID- 16618994
TI  - Peri-implant tissue healing in implant placed in post-extraction sockets of
      maxillary premolars.
AB  - AIM: The aim of this study was the clinical and radiographic evaluation of peri
      implant tissues healing associated with two-stage implants performed with one
      stage surgery and placed into post-extraction sockets of maxillary premolars.
      METHODS: Ten natural tapered submerged titanium implants with double acid-etched
      surface were installed in post-extraction sockets of maxillary premolars showing
      no bone dehiscence or fenestrations. Implants were selected according to the
      greatest dimension compatible to vertical and horizontal diameters of the post
      extraction sockets. Peri-implant defects showing more than 2 mm of distance
      between the marginal palatal bone and the implant margin, were not treated with a
      regenerative procedure but with a bone swaging technique by means of
      piezoelectric surgery. At 16 weeks osteointegration of implants was examined with
      a clinical and standardized radiographic evaluation. RESULTS: All patients showed
      good clinical healing without any complication. At 16 weeks all implants, either
      those with reduced marginal defect or those with modified crestal bone profile,
      were osteointegrated. CONCLUSIONS: The use of two-stage implants performed with
      one-stage surgery in 4 walls post-extraction sockets of maxillary premolars,
      seems to allow osteointegration both in reduced peri-implant horizontal defects
      as well as in defects larger than 2 mm. Furthermore, these procedures seem to
      simplify the management of soft peri-implant tissues.

PMID- 16618995
TI  - Salivary glands tumours: a retrospective study of 454 patients.
AB  - AIM: Salivary glands tumors constitute a highly heterogeneous group in human
      oncological pathology. They show different clinical, epidemiological,
      histopathological and evolutionary characteristics. METHODS: In this paper we
      have analysed their epidemiological aspects in 454 patients with salivary glands
      tumors surgically treated at the Maxillofacial Surgical Unit of the Azienda
      Ospedaliero-Universitaria ''Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi'',
      Ancona, Italy, from 1990 to 2002, to evaluate the incidence of the different
      types of neoplasia and their age and sex distribution. RESULTS: Our results show
      that 63.22% of salivary glands tumors occur in the parotid gland, with a
      predominance of benign tumours, pleomorphic adenoma being the most prevalent
      histological type. A higher prevalence was observed in the female sex.
      CONCLUSIONS: Malignant tumors were more common in the elderly than in young
      patients and the most common histological types were mucoepidermoid carcinoma and
      adenoid cystic carcinoma.

PMID- 16618996
TI  - Maxillary ameloblastoma.
AB  - Maxillary ameloblastoma is a rare odontogenic neoplasm that is histologically
      benign and originates from epithelial cells present in bone tissue. If excised
      through conservative surgery, this tumour has a high relapse rate and is locally
      aggressive. The risk, in particularly extensive forms, that the ameloblastoma
      will invade extra-maxillary structures such as the orbit, the pterygomaxillary
      fossa, the infratemporal fossa and the base of the skull, means that surgical
      treatment is difficult if it is to be oncologically radical while respecting
      function and aesthetics. Thus, in these cases a complete and in-depth diagnostic
      work-up and careful planning of surgical treatment are needed: surgery entails an
      ablative phase with en-bloc resection of the neoformation to margins free of
      neoplastic infiltration, and a reconstruction phase that, within a short time
      frame, will re-establish functionality and provide a good aesthetic result. Our
      experience in treating 2 cases of maxillary ameloblastoma is reported.

PMID- 16618997
TI  - Radiological evaluation of major salivary glands agenesis. A case report.
AB  - Congenital agenesis of major salivary glands is a rare entity with unclear
      etiopathogenesis, sometimes presenting in a bilateral form. This pathologic
      condition is often diagnosed with delay because of the poor clinical
      presentation. Only bilateral forms of parotid aplasia are responsible of such a
      severe lack of saliva causing dental caries, periodontal diseases, ascending
      sialadenitis and candidosis. In most cases, the aplasia involves more than a
      single major salivary gland and is occasionally associated with other
      developmental anomalies of the head-neck region. A case is presented in which an
      aplasia of the right parotid gland is associated with hypoplasia of the thyroid's
      right lobe and homolateral angioma of the homolateral cheek. We report the
      clinical and radiological findings in our patient and a review of the diagnostic
      imaging approach in such anomalies.

PMID- 16618998
TI  - Central odontogenic fibroma interesting the maxillary sinus. A case report and
      literature survey.
AB  - Odontogenic fibroma (OF) is a rare benign odontogenic tumor deriving from the
      dental mesenchymal tissue and accounting for less than 5% of all odontogenic
      tumors. This paper presents an aggressive histologically diagnosed central
      odontogenic fibroma (COF) in a 17-year-old girl characterized by asymptomatic
      rapid growth with massive replenishment of the left maxillary sinus. We carried
      out a review of the literature to retrieve all published cases of COF especially
      focused on radiographic aspects and surgical treatment of cases characterized by
      clinical aggressive behaviour, as we observed in our patient. Search strategy
      included retrieval of English language papers, published from 1966 to today, in
      dental journals on MEDLINE/PubMed and EMBASE, and hand-searching of the
      bibliography of retrieved papers. Sixty-nine cases of COF were identified from
      1954 to 2003 and a new one was added. We have compared characteristics of COFs
      according to age, gender, location, clinical and radiographic findings of
      aggressive development, and histology. We discuss clinical and radiographic
      aspects of our case compared with COFs previously published. We give suggestions
      for surgical treatment of COF in case of aggression to important anatomical
      structures.

PMID- 16618999
TI  - Immediate loading on single NobelDirect implant. Case report.
AB  - A problem associated with implant-prosthetic rehabilitation on single implant is
      the unscrewing or fracture of the connecting screw. In this study the authors
      evaluate clinical results of the immediate loading on single NobelDirect implant.
      This innovative implant introduced by NobelBiocare is a single-piece implant
      including fixture and abutment in a single piece of Titanium in order to
      eliminate the problem of unscrewing or fracture of the connecting screw.

PMID- 16619000
TI  - Mismatch repair protein expression and microsatellite instability: a comparison
      of clear cell sarcoma of soft parts and metastatic melanoma.
AB  - Clear cell sarcoma of soft parts is a rare soft tissue malignancy that shows
      phenotypic overlap with cutaneous melanoma but can be distinguished by the
      presence of a t(12;22) translocation. Microsatellite instability (MSI), a
      variation in the lengths of short repeat DNA segments in the genome, has been
      implicated in melanoma tumorigenesis, but is rare or absent in clear cell
      sarcoma. Defects in the mismatch repair (MMR) enzyme complex correlate with MSI
      in some tumor types, allowing the use of immunohistochemistry for the MMR
      proteins hMLH1 and hMSH2 to predict the presence of MSI. To determine if the
      association between MMR defects and MSI extends to clear cell sarcoma, we
      compared a group of nine clear cell sarcomas to 11 metastatic melanomas on the
      basis of MSI and the expression of MMR proteins. MSI was studied using
      fluorescence-based multiplexed PCR of five loci. Immunohistochemistry was
      evaluated on formalin-fixed paraffin-embedded tissue for hMLH1, hMHS2 and hMSH6.
      MSI was present in only 1/9 (11%) clear cell sarcoma case and in 8/11 (73%)
      melanoma cases. Immunostaining for hMLH1 and hMSH2 was preserved in all the clear
      cell sarcomas but loss of immunostaining for one or both proteins was seen in
      6/11 melanomas (55%). hMSH6 was detected in 7/9 (78%) clear cell sarcomas and
      10/11 (91%) of melanomas. Clear cell sarcoma and metastatic melanoma differed
      significantly with respect to the presence of MSI (P=0.010) and staining for
      hMLH1 and/or hMSH2 (P=0.014) but not hMSH6 (P=0.57). Mismatch repair, and
      consequently genomic instability may contribute to tumorigenesis in melanoma but
      not clear cell sarcoma. Immunostaining for hMLH1 and hMSH2 and MSI analysis may
      be helpful in the differential diagnosis of large soft tissue or visceral
      malignancies with melanocytic differentiation.

PMID- 16619001
TI  - Characterization of acrylic polyamide plastic embolization particles in vitro and
      in human tissue sections by light microscopy, infrared microspectroscopy and
      scanning electron microscopy with energy dispersive X-ray analysis.
AB  - Vascular embolization is a well-established practice for the treatment of tumors
      and vascular lesions. Rounded beads (microspheres) of various materials
      (collagen, dextran and trisacryl-polymer-gelatin) were developed to solve
      problems encountered with earlier versions of embolic material. We performed
      histochemistry, Fourier transform infrared microspectroscopy and scanning
      electron microscopy with energy dispersive X-ray analysis on two uterine and one
      hepatic specimen with unidentified intravascular foreign material, and examined a
      reference embolization product for comparison. The hematoxylin and eosin stained
      tissue sections showed multiple foci with unidentified intravascular foreign
      material and fibrous obliteration of vessel lumens. Only one case had a clinical
      history of previous embolization but without specifying the material used. One
      case was submitted for identification of a 'parasite'. The material stained
      positively with Sirius red and mucicarmine, variably with Masson's trichrome
      stain and Movat pentachrome, and did not stain centrally with periodic acid
      Schiff with diastase. Infrared spectrophotometric analysis of the material from
      all three cases demonstrated the spectrum of acrylic polyamide plastic. A control
      sample of EmboGold exhibited infrared microspectroscopic spectra similar to the
      three tissue specimens. Analysis by scanning electron microscopy with energy
      dispersive X-ray analysis demonstrated some differences in elemental composition
      between the tissue sections and the selected reference material. To our
      knowledge, this is the first report of infrared spectrophotometric analysis with
      scanning electron microscopy with energy dispersive X-ray analysis of an acrylic
      polyamide plastic embolization product both in vitro and in human histologic
      tissue sections. In cases lacking appropriate clinical information,
      identification by these methods and/or a panel of special stains may assist
      pathologists unfamiliar with this material's light microscopic appearance.

PMID- 16619002
TI  - Mice doubly deficient in the midkine and pleiotrophin genes exhibit deficits in
      the expression of beta-tectorin gene and in auditory response.
AB  - alpha-Tectorin and beta-tectorin are major noncollagenous proteins of the
      tectorial membrane, which plays a crucial role in the reception of sonic signals
      in the cochlea. Midkine and pleiotrophin are closely related proteins that serve
      as growth factors and cytokines. In mice doubly deficient in the midkine gene and
      pleiotrophin gene, expression of beta-tectorin mRNA was nearly abolished in the
      cochlea on day 1 and 7 after birth. Expression of alpha-tectorin mRNA was
      unaffected in the double knockout mice, and expression of beta-tectorin mRNA was
      not altered in mice deficient in only the midkine or pleiotrophin gene. In
      newborn wild-type mice, both midkine and pleiotrophin were expressed in the
      greater epithelial ridge of the cochlea, in which beta-tectorin mRNA was strongly
      expressed. These results indicate that either midkine or pleiotrophin is required
      for significant expression of beta-tectorin. In agreement with the view that beta
      tectorin is essential for normal auditory function, mice doubly deficient in both
      midkine and pleiotrophin genes exhibited very severe auditory deficits. We
      observed that mice deficient in either midkine or pleiotrophin gene were also
      impaired in their auditory response, but the level of the deficit was generally
      low or moderate. The present finding illustrates the importance of growth factor
      expression in the cochlea for auditory function.

PMID- 16619003
TI  - Crosstalk between PDGF and IGF-I receptors in rat liver myofibroblasts:
      implication for liver fibrogenesis.
AB  - Insulin-like growth factor I (IGF-I) and platelet-derived growth factor (PDGF)
      have been identified as significant mitogens for liver myofibroblasts (LMFs), one
      of the cell populations playing a role in liver fibrogenesis. In the present
      work, we aimed to elucidate a possible interaction between PDGF receptor (PDGFR)
      and IGF-I receptor (IGF-IR) signaling in LMFs. Among different rat liver cells,
      PDGFR alpha- and beta-subunits were mainly expressed in hepatic stellate cells
      and LMFs, and were upregulated during their in vitro cultivation. In LMFs, PDGF
      BB (10 ng/ml) stimulated DNA synthesis approximately two-fold and this effect was
      similar to that of IGF-I. IGF-I and PDGF-BB differentially affected IGF-IR and
      PDGFR signaling. High concentrations of IGF-I decreased levels of IGF-IR and IRS
      1 and inhibited the expression and activation of PDGFRalpha. PDGF-BB prevented
      IGF-I-induced downregulation of the IGF-IR, but did not affect expression of its
      cognate receptor subunits. Transphosphorylation of PDGFR and IGF-IR was not
      observed. PDGF effectively activated terminal MAP kinases, PI3 kinase and Akt
      kinase, whereas IGF-I demonstrated weaker effects. PLCgamma(1) was phosphorylated
      only in response to PDGF, but not to IGF-I. In rat LMFs, blockade of the IGF-IR
      via inhibition of the IGF-IR kinase completely abrogated IGF- and PDGF-induced
      mitogenesis and the ability of PDGF to phosphorylate PLCgamma(1). In conclusion,
      the presented data demonstrate that the PDGFR signaling requires a functional IGF
      IR and that PDGF-BB stabilizes the IGF-IR function through preventing the IGF-I
      induced downregulation of the IGF-IR. These interactions might be relevant in
      vivo for the fibroproliferative response during liver injury.

PMID- 16619004
TI  - Hepatic stellate cells primed with cytokines upregulate inflammation in response
      to peptidoglycan or lipoteichoic acid.
AB  - Gram-positive bacterial products such as peptidoglycan (PGN) and lipoteichoic
      acid (LTA) are potent stimulators of innate inflammatory responses. We previously
      reported that lipopolysaccharide (LPS), a major biologically active agent of gram
      negative bacteria, induces a proinflammatory response via the Toll-like receptor
      (TLR) 4 in hepatic stellate cells (HSCs). Here we investigated the mechanism of
      proinflammatory action by PGN and LTA in activated human HSCs. Following
      treatment with either TNF-alpha or IL-1beta, expression of TLR2 and CD14 was
      determined by real-time PCR and Western blotting. NF-kappaB activation was
      assessed by NF-kappaB-driven luciferase assay and electrophoretic mobility shift
      assay. Interleukin-8 (IL-8) from culture supernatant was measured by ELISA.
      Activated human HSCs express TLR2 and CD14, which are receptors for PGN and LTA
      signaling. TNF-alpha and IL-1beta significantly upregulated the expression of
      TLR2 mRNA and protein in HSCs. PGN and LTA induced NF-kappaB activation and
      stimulated production of IL-8 in HSCs. Pretreatment with TNF-alpha or IL-1beta
      augmented NF-kappaB activation and IL-8 production in response to PGN or LTA.
      Both PGN- and LTA-induced NF-kappaB activation and IL-8 secretion were completely
      inhibited by anti-TLR2 blocking antibody (T2.5). These findings suggest that TNF
      alpha or IL-1beta primed HSCs enhance the production of IL-8 in response to PGN
      and LTA through augmentation of the TLR2 system.

PMID- 16619005
TI  - The environment and human health.

PMID- 16619009
TI  - Modulation of inflammation by extracellular nucleotides.
AB  - In this issue, Seiffert et al. show that adenosine triphosphate enhances the
      production of inflammatory mediators by human dermal endothelial cells. However,
      a growing literature shows that adenosine triphosphate exerts anti-inflammatory
      effects, partly by inducing a semi-maturation of dendritic cells associated with
      immune tolerance. These discrepancies can be reconciled knowing that
      extracellular nucleotides constitute danger signals that are released in response
      to both external aggression (chemical, microbial) and excess inflammation.

PMID- 16619010
TI  - Kit and melanocyte migration.
AB  - As described in this issue, Alexeev and Yoon introduced a Kit-activating mutation
      into melanocytes. Although mitogenic in mast cells, this mutation was motogenic
      in melanocytes. Further, melanocytes had a reduced proliferative rate and were
      less differentiated. The disparate response may be due to differences in the
      cellular milieu of melanocytes and may have implications for normal melanocytic
      integration into the epidermis, nevogenesis, and melanoma.

PMID- 16619011
TI  - Functioning methionine-S-sulfoxide reductases A and B are present in human skin.
AB  - Methionine residues in the structure of proteins and peptides are especially
      sensitive to oxidation by hydrogen peroxide (H(2)O(2)) yielding both the (R) and
      (S) diastereomers of methionine sulfoxide. This commentary shows that both
      diastereomers of methionine sulfoxide (R and S) can be repaired in the human
      epidermis by methionine sulfoxide reductases A and B, respectively.

PMID- 16619012
TI  - "Out, damned spot!".
AB  - Mice transgenic for the Kit Val620Ala mutation, which in humans has been
      associated with progressive piebaldism, exhibit dominant white spotting but show
      no evidence of progressive depigmentation. These results are consistent with the
      previous hypothesis that progressive piebaldism might result from digenic
      inheritance, of the KIT(V620A) mutation that causes piebaldism and a second,
      unknown locus that causes progressive depigmentation.

PMID- 16619013
TI  - Lipid rafts: membrane triage centers.
AB  - Both biochemical and live cell imaging studies suggest the existence of lipid
      rafts, specialized membrane microdomains that promote interaction among signaling
      molecules. Although their composition is still poorly understood, these highly
      dynamic domains are enriched in cholesterol, sphingolipids, and particular groups
      of proteins. The mechanism(s) by which trafficking into or out of lipid rafts
      affects signaling remains unclear.

PMID- 16619015
TI  - Keeping chemistry in the equation.

PMID- 16619016
TI  - The integration of cell and chemical biology in protein folding.
AB  - Eukaryotic cells are specialized, interdependent functional units of complex
      tissues that are composed of metabolically integrated systems defined by
      chemically distinct organelles that operate as reaction vessels. It is now clear
      that the small-molecule and polymer-based composition of these organelles plays a
      crucial role in generating and maintaining protein folds and functions through
      the systems chemistry of the local environments.

PMID- 16619017
TI  - Fishing and frogging for anti-angiogenic drugs.

PMID- 16619018
TI  - Metalloproteases see the light.

PMID- 16619019
TI  - A library of RNA bridges.

PMID- 16619020
TI  - Remarkable structural variation within fatty acid megasynthases.

PMID- 16619021
TI  - Redox sensing and histidine oxidation: no longer PerR-fect strangers.

PMID- 16619023
TI  - Sweet spots in functional glycomics.
AB  - Information contained in the mammalian glycome is decoded by glycan-binding
      proteins (GBPs) that mediate diverse functions including host-pathogen
      interactions, cell trafficking and transmembrane signaling. Although information
      on the biological roles of GBPs is rapidly expanding, challenges remain in
      identifying the glycan ligands and their impact on GBP function. Protein-glycan
      interactions are typically low affinity, requiring multivalent interactions to
      achieve a biological effect. Though many glycoproteins can carry the glycan
      structure recognized by the GBP, other factors, such as recognition of protein
      epitopes and microdomain localization, may restrict which glycoproteins are
      functional ligands in situ. Recent advances in development of glycan arrays,
      synthesis of multivalent glycan ligands, bioengineering of cell-surface glycans
      and glycomics databases are providing new tools to identify the ligands of GBPs
      and to elucidate the mechanisms by which they participate in GBP function.

PMID- 16619024
TI  - The molecular chaperone Hsp90 delivers precursor proteins to the chloroplast
      import receptor Toc64.
AB  - Precursor protein targeting toward organellar surfaces is assisted by different
      cytosolic chaperones. We demonstrate that the chloroplast protein translocon
      subunit Toc64 is the docking site for Hsp90 affiliated preproteins. Thereby,
      Hsp90 is recognised by the clamp type TPR domain of Toc64. The subsequent
      transfer of the preprotein from Toc64 to the major receptor of the Toc complex,
      namely Toc34, is affinity driven and nucleotide dependent. We propose that Toc64
      acts as an initial docking site for Hsp90 associated precursor proteins. We
      outline a mechanism in which chaperones are recruited for a specific targeting
      event by a membrane-inserted receptor.

PMID- 16619025
TI  - Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism
      of antithrombin activation.
AB  - Regulation of blood coagulation is critical for maintaining blood flow, while
      preventing excessive bleeding or thrombosis. One of the principal regulatory
      mechanisms involves heparin activation of the serpin antithrombin (AT).
      Inhibition of several coagulation proteases is accelerated by up to 10,000-fold
      by heparin, either through bridging AT and the protease or by inducing allosteric
      changes in the properties of AT. The anticoagulant effect of short heparin
      chains, including the minimal AT-specific pentasaccharide, is mediated
      exclusively through the allosteric activation of AT towards efficient inhibition
      of coagulation factors (f) IXa and Xa. Here we present the crystallographic
      structure of the recognition (Michaelis) complex between heparin-activated AT and
      S195A fXa, revealing the extensive exosite contacts that confer specificity. The
      heparin-induced conformational change in AT is required to allow simultaneous
      contacts within the active site and two distinct exosites of fXa (36-loop and the
      autolysis loop). This structure explains the molecular basis of protease
      recognition by AT, and the mechanism of action of the important therapeutic low
      molecular-weight heparins.

PMID- 16619026
TI  - The Hrd1p ligase complex forms a linchpin between ER-lumenal substrate selection
      and Cdc48p recruitment.
AB  - Misfolded proteins of the endoplasmic reticulum (ER) are targeted to the
      cytoplasm for proteasomal degradation. Key components of this process are ER
      membrane-bound ubiquitin ligases. These ligases associate with the cytoplasmic
      AAA-ATPase Cdc48p/p97, which is thought to support the release of malfolded
      proteins from the ER. Here, we characterize a yeast protein complex containing
      the ubiquitin ligase Hrd1p and the ER membrane proteins Hrd3p and Der1p. Hrd3p
      binds malfolded proteins in the ER lumen enabling their delivery to downstream
      components. Therefore, we propose that Hrd3p acts as a substrate recruitment
      factor for the Hrd1p ligase complex. Hrd3p function is also required for the
      association of Cdc48p with Hrd1p. Moreover, our data demonstrate that recruitment
      of Cdc48p depends on substrate processing by the Hrd1p ligase complex. Thus, the
      Hrd1p ligase complex unites substrate selection in the ER lumen and
      polyubiquitination in the cytoplasm and links these processes to the release of
      ER proteins via the Cdc48p complex.

PMID- 16619027
TI  - Definition of the bacterial N-glycosylation site consensus sequence.
AB  - The Campylobacter jejuni pgl locus encodes an N-linked protein glycosylation
      machinery that can be functionally transferred into Escherichia coli. In this
      system, we analyzed the elements in the C. jejuni N-glycoprotein AcrA required
      for accepting an N-glycan. We found that the eukaryotic primary consensus
      sequence for N-glycosylation is N terminally extended to D/E-Y-N-X-S/T (Y, X not
      equalP) for recognition by the bacterial oligosaccharyltransferase (OST) PglB.
      However, not all consensus sequences were N-glycosylated when they were either
      artificially introduced or when they were present in non-C. jejuni proteins. We
      were able to produce recombinant glycoproteins with engineered N-glycosylation
      sites and confirmed the requirement for a negatively charged side chain at
      position -2 in C. jejuni N-glycoproteins. N-glycosylation of AcrA by the
      eukaryotic OST in Saccharomyces cerevisiae occurred independent of the acidic
      residue at the -2 position. Thus, bacterial N-glycosylation site selection is
      more specific than the eukaryotic equivalent with respect to the polypeptide
      acceptor sequence.

PMID- 16619028
TI  - Src kinase phosphorylates Caspase-8 on Tyr380: a novel mechanism of apoptosis
      suppression.
AB  - We identified Caspase-8 as a new substrate for Src kinase. Phosphorylation occurs
      on Tyr380, situated in the linker region between the large and the small subunits
      of human Procaspase-8, and results in downregulation of Caspase-8 proapoptotic
      function. Src activation triggers Caspase-8 phosphorylation on Tyr380 and impairs
      Fas-induced apoptosis. Accordingly, Src failed to protect Caspase-8-defective
      human cells in which a Caspase-8-Y380F mutant is expressed from Fas-induced cell
      death. Remarkably, Src activation upon EGF-receptor stimulation triggers
      endogenous Caspase-8 phosphorylation and prevents Fas-induced apoptosis. Tyr380
      is phosphorylated also in human colon cancers where Src is aberrantly activated.
      These data provide the first evidence for a direct role of tyrosine
      phosphorylation in the control of caspases and reveal a new mechanism through
      which tyrosine kinases inhibit apoptosis and participate in tumor progression.

PMID- 16619029
TI  - Role of SGT1 in resistance protein accumulation in plant immunity.
AB  - A highly conserved eukaryotic protein SGT1 binds specifically to the molecular
      chaperone, HSP90. In plants, SGT1 positively regulates disease resistance
      conferred by many Resistance (R) proteins and developmental responses to the
      phytohormone, auxin. We show that silencing of SGT1 in Nicotiana benthamiana
      causes a reduction in steady-state levels of the R protein, Rx. These data
      support a role of SGT1 in R protein accumulation, possibly at the level of
      complex assembly. In Arabidopsis, two SGT1 proteins, AtSGT1a and AtSGT1b, are
      functionally redundant early in development. AtSGT1a and AtSGT1b are induced in
      leaves upon infection and either protein can function in resistance once a
      certain level is attained, depending on the R protein tested. In unchallenged
      tissues, steady-state AtSGT1b levels are at least four times greater than
      AtSGT1a. While the respective tetratricopeptide repeat (TPR) domains of SGT1a and
      SGT1b control protein accumulation, they are dispensable for intrinsic functions
      of SGT1 in resistance and auxin responses.

PMID- 16619030
TI  - The 20S proteasome processes NF-kappaB1 p105 into p50 in a translation
      independent manner.
AB  - The NF-kappaB p50 is the N-terminal processed product of the precursor, p105. It
      has been suggested that p50 is generated not from full-length p105 but
      cotranslationally from incompletely synthesized molecules by the proteasome. We
      show that the 20S proteasome endoproteolytically cleaves the fully synthesized
      p105 and selectively degrades the C-terminus of p105, leading to p50 generation
      in a ubiquitin-independent manner. As small as 25 residues C-terminus to the site
      of processing are sufficient to promote processing in vivo. However, any p105
      mutant that lacks complete ankyrin repeat domain (ARD) is processed aberrantly,
      suggesting that native processing must occur from a precursor, which extends
      beyond the ARD. Remarkably, the mutant p105 that lacks the internal region
      including the glycine-rich region (GRR) is completely degraded by 20S proteasome
      in vitro. This suggests that the GRR impedes the complete degradation of the p105
      precursor, thus contributing to p50 generation.

PMID- 16619031
TI  - A CDK-catalysed regulatory phosphorylation for formation of the DNA replication
      complex Sld2-Dpb11.
AB  - Phosphorylation often regulates protein-protein interactions to control
      biological reactions. The Sld2 and Dpb11 proteins of budding yeast form a
      phosphorylation-dependent complex that is essential for chromosomal DNA
      replication. The Sld2 protein has a cluster of 11 cyclin-dependent kinase (CDK)
      phosphorylation motifs (Ser/Thr-Pro), six of which match the canonical sequences
      Ser/Thr-Pro-X-Lys/Arg, Lys/Arg-Ser/Thr-Pro and Ser/Thr-Pro-Lys/Arg. Simultaneous
      alanine substitution for serine or threonine in all the canonical CDK
      phosphorylation motifs severely reduces complex formation between Sld2 and Dpb11,
      and inhibits DNA replication. Here we show that phosphorylation of these
      canonical motifs does not play a direct role in complex formation, but rather
      regulates phosphorylation of another residue, Thr84. This constitutes a non
      canonical CDK-phosphorylation motif within a 28-amino-acid sequence that is
      responsible, after phosphorylation, for binding of Sld2-Dpb11. We further suggest
      that CDK-catalysed phosphorylation of sites other than Thr84 renders Thr84
      accessible to CDK. Finally, we argue that this novel mechanism sets a threshold
      of CDK activity for formation of the essential Sld2 to Dpb11 complex and
      therefore prevents premature DNA replication.

PMID- 16619032
TI  - An aging pathway controls the TrkA to p75NTR receptor switch and amyloid beta
      peptide generation.
AB  - Aging of the brain is characterized by marked changes in the expression levels of
      the neurotrophin receptors, TrkA and p75(NTR). An expression pattern in which
      TrkA predominates in younger animals switches to one in which p75(NTR)
      predominates in older animals. This TrkA-to-p75(NTR) switch is accompanied by
      activation of the second messenger ceramide, stabilization of beta-site amyloid
      precursor protein-cleaving enzyme-1 (BACE1), and increased production of amyloid
      beta-peptide (Abeta). Here, we show that the insulin-like growth factor-1
      receptor (IGF1-R), the common regulator of lifespan and age-related events in
      many different organisms, is responsible for the TrkA-to-p75(NTR) switch in both
      human neuroblastoma cell lines and primary neurons from mouse brain. The
      signaling pathway that controls the level of TrkA and p75(NTR) downstream of the
      IGF1-R requires IRS2, PIP3/Akt, and is under the control of PTEN and p44, the
      short isoform of p53. We also show that hyperactivation of IGF1-R signaling in
      p44 transgenic animals, which show an accelerated form of aging, is characterized
      by early TrkA-to-p75(NTR) switch and increased production of Abeta in the brain.

PMID- 16619033
TI  - PDGF regulates the actin cytoskeleton through hnRNP-K-mediated activation of the
      ubiquitin E3-ligase MIR.
AB  - PDGF is a potent chemotactic mitogen and a strong inductor of fibroblast
      motility. In Swiss 3T3 fibroblasts, exposure to PDGF but not EGF or IGF-1 causes
      a rapid loss of actin stress fibers (SFs) and focal adhesions (FAs), which is
      followed by the development of retractile dendritic protrusions and induction of
      motility. The PDGF-specific actin reorganization was blocked by inhibition of Src
      kinase and the 26S proteasome. PDGF induced Src-dependent association between the
      multifunctional transcription/translation regulator hnRNP-K and the mRNA-encoding
      myosin regulatory light-chain (MRLC)-interacting protein (MIR), a E(3)-ubiquitin
      ligase that is MRLC specific. This in turn rapidly increased MIR expression, and
      led to ubiquitination and proteasome-mediated degradation of MRLC. Downregulation
      of MIR by RNA muting prevented the reorganization of actin structures and
      severely reduced the migratory and wound-healing potential of PDGF-treated cells.
      The results show that activation of MIR and the resulting removal of
      diphosphorylated MRLC are essential for PDGF to instigate and maintain control
      over the actin-myosin-based contractile system in Swiss 3T3 fibroblasts. The PDGF
      induced protein destabilization through the regulation of hnRNP-K controlled
      ubiquitin -ligase translation identifies a novel pathway by which external
      stimuli can regulate phenotypic development through rapid, organelle-specific
      changes in the activity and stability of cytoskeletal regulators.

PMID- 16619034
TI  - Proline oxidase activates both intrinsic and extrinsic pathways for apoptosis:
      the role of ROS/superoxides, NFAT and MEK/ERK signaling.
AB  - Proline oxidase (POX), often considered a 'housekeeping enzyme' might play an
      important role in apoptosis. We have shown that POX generated proline-dependent
      reactive oxygen species (ROS), specifically superoxide radicals, and induced
      apoptosis through the mitochondrial (intrinsic) pathway. In our current report,
      we used DLD-1 colorectal cancer cells stably transfected with the POX gene under
      the control of a tetracycline-inducible promoter and found POX-stimulated
      expression of tumor necrosis factor-related apoptosis inducing ligand (TRAIL),
      DR5 and cleavage of caspase-8. Importantly, apoptosis measured by flow cytometry
      was partially inhibited by Z-IETD-FMK, a specific inhibitor of caspase-8. These
      findings suggest that the extrinsic (death receptor) pathway also is activated by
      POX. Furthermore, the mechanism of this effect on the extrinsic pathway,
      specifically, the induction of TRAIL by POX, may be mediated by NFAT
      transcription factors. Additionally, POX expression also dramatically decreased
      phosphorylation of MEK and ERK, and the decrease was partially reversed by
      expression of manganese superoxide dismutase (MnSOD). Overexpression of
      constitutively active form of MEK, acMEK, partially blocked POX-induced
      apoptosis. These findings suggest the involvement of MEK/ERK signaling and
      further confirm the role of ROS/superoxides in POX-induced apoptosis. Combined
      with previously published data, we conclude that POX may induce apoptosis through
      both intrinsic and extrinsic pathways and is involved in nuclear factor of
      activated T cells (NFAT) signaling and regulation of the MEK/ERK pathway. It is
      suggested that, as a nutrition factor, POX may modulate apoptosis signals induced
      by p53 or other anti-cancer agents and enhance apoptosis in stress situations.

PMID- 16619035
TI  - Gene amplification and overexpression of protein phosphatase 1alpha in oral
      squamous cell carcinoma cell lines.
AB  - Gene amplification of chromosomal band 11q13 is observed frequently in oral
      squamous cell carcinomas (OSCC). Several genes have been identified in the 11q13
      amplicon, including FGF3, FGF4, CCND1, EMS1 and TAOS1. Some of these genes show
      good correlation between gene copy number and gene expression, and are thought to
      play a role in driving 11q13 amplification. The PPP1CA gene, which encodes the
      catalytic subunit of serine/threonine protein phosphatase protein phosphatase
      1alpha (PP1alpha), is also located in 11q13. Protein phosphatase 1alpha, one of
      the isoforms of PP1, regulates critical cellular events, such as cell cycle
      progression, and apoptosis. We sought to explore the possibility that PPP1CA was
      amplified and overexpressed in OSCC cells. Indeed, some OSCC cell lines had
      PPP1CA gene amplification, as analysed by fluorescence in situ hybridization. We
      have also demonstrated that PPP1CA gene copy number is increased in 21% of the
      OSCC cell lines determined by quantitative microsatellite analysis. PP1alpha RNA
      expression determined by quantitative reverse transcription-polymerase chain
      reaction was significantly higher in OSCC cell lines with 11q13 amplification
      compared to those without 11q13 amplification (P=0.011). The difference was even
      more significant between cell lines with at least three copies of the PPP1CA gene
      and those with less than three copies of the gene (P=0.00045). Relative PP1alpha
      protein levels were also significantly associated with PPP1CA gene copy number
      (P=0.014). Furthermore, knockdown of PP1alpha and/or cyclin D1 by small
      interfering RNA suppressed OSCC cell growth, at least in part by modulating pRB
      phosphorylation, resulting in G0 growth arrest. These data suggest that like the
      cyclin D1 gene, CCND1, amplification and overexpression of the PP1alpha gene,
      PPP1CA, may be involved in OSCC tumorigenesis and/or progression.

PMID- 16619036
TI  - Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell
      plasticity through a JNK-dependent mechanism.
AB  - Environmental chemicals such as dioxin adversely affect immune, neurological and
      reproductive functions and have been implicated in cancer development. However,
      the mechanisms responsible for dioxin toxicity are still poorly understood. Here,
      we show that dioxin and related pollutants trigger a marked morphological change
      in epithelial cells that remodel their cytoskeleton to increase interaction with
      extra cellular matrix while loosening cell-cell contacts. Furthermore, dioxin
      treated cells show increased motility. These dioxin-mediated effects are mimicked
      by constitutive expression and activation of the intracellular dioxin receptor
      (aryl hydrocarbon receptor (AhR)). They correlate with activation of the Jun NH2
      terminal kinase (JNK) and are reverted by treatment with a JNK inhibitor. Dioxin
      induced effects occur 48 h post-treatment initiation, a time scale, which argues
      for a genomic effect of the AhR, linked to induction of target genes. This novel
      Ahr action on cell plasticity points to a role in cancer progression.

PMID- 16619037
TI  - Cited2 modulates TGF-beta-mediated upregulation of MMP9.
AB  - Cited (CBP/p300-interacting transactivators with glutamic acid (E)/aspartic acid
      (D)-rich C-terminal domain) 2, which is a CBP/p300-binding transcription co
      activator without typical DNA-binding domains, has been implicated in control of
      cell growth and malignant transformation in Rat1 cells. In this report, we
      provide evidence that Cited2 is an important regulator of transforming growth
      factor (TGF)-beta signaling. Overexpression of Cited2 enhanced TGF-beta-mediated
      transcription of a Smad-Binding Element-containing luciferase reporter construct,
      SBE4-Luc. This may occur through a direct physical association of Cited2 with
      Smads 2 and 3, as supported by co-immunoprecipitation, mammalian two-hybrid and
      glutathione S-transferase-pull down assays. The transcription factor p300, which
      binds to Smad3, was shown to further enhance the interaction between Cited2 and
      Smad3, and the transcriptional responses of Smad3 by Cited2 in reporter assays.
      Cited2 enhances TGF-beta-mediated upregulation of matrix metalloproteinase 9
      (MMP9) in Cited2 inducible mouse embryo fibroblasts. Overexpression of Cited2
      enhanced TGF-beta-mediated MMP9 promoter reporter activity. Moreover, knockdown
      of Cited2 in MDA-MB-231 cells attenuated TGF-beta-mediated upregulation of MMP9
      and TGF-beta-mediated cell invasion. Chromatin immunoprecipitation showed that
      Cited2 and Smad3 were recruited to MMP9 promoter upon TGF-beta stimulation. This
      is the first demonstration that Cited2 functions as a Smad3/p300-interacting
      transcriptional co-activator in modulating the expression of MMP9, which could
      affect tumor cell invasion mediated by TGF-beta.

PMID- 16619038
TI  - Mortalin controls centrosome duplication via modulating centrosomal localization
      of p53.
AB  - Abnormal amplification of centrosomes, commonly found in human cancer, is the
      major cause of mitotic defects and chromosome instability in cancer cells. Like
      DNA, centrosomes duplicate once in each cell cycle, hence the defect in the
      mechanism that ensures centrosome duplication to occur once and only once in each
      cell cycle results in abnormal amplification of centrosomes and mitotic defects.
      Centrosomes are non-membranous organelles, and undergo dynamic changes in its
      constituents during the centrosome duplication cycle. Through a comparative mass
      spectrometric analysis of unduplicated and duplicated centrosomes, we identified
      mortalin, a member of heat shock protein family, as a protein that associates
      preferentially with duplicated centrosomes. Further analysis revealed that
      mortalin localized to centrosomes in late G1 before centrosome duplication,
      remained at centrosomes during S and G2, and dissociated from centrosomes during
      mitosis. Overexpression of mortalin overrides the p53-dependent suppression of
      centrosome duplication, and mortalin-driven centrosome duplication requires
      physical interaction between mortalin and p53. Moreover, mortalin promotes
      dissociation of p53 from centrosomes through physical interaction. The p53 mutant
      that lacks the ability to bind to mortalin remains at centrosomes, and suppresses
      centrosome duplication in a transactivation function-independent manner. Thus,
      our present findings not only identify mortalin as an upstream molecule of p53
      but also provide evidence for the involvement of centrosomally localized p53 in
      the regulation of centrosome duplication.

PMID- 16619039
TI  - Restoration of SHIP-1 activity in human leukemic cells modifies NF-kappaB
      activation pathway and cellular survival upon oxidative stress.
AB  - Nuclear factor-kappa B (NF-kappaB) is an important prosurvival transcription
      factor activated in response to a large array of external stimuli, including
      reactive oxygen species (ROS). Previous works have shown that NF-kappaB
      activation by ROS involved tyrosine phosphorylation of the inhibitor IkappaBalpha
      through an IkappaB kinase (IKK)-independent mechanism. In the present work, we
      investigated with more details NF-kappaB redox regulation in human leukemic
      cells. By using different cell lines (CEM, Jurkat and the subclone Jurkat JR), we
      clearly showed that NF-kappaB activation by hydrogen peroxide (H2O2) is cell-type
      dependent: it activates NF-kappaB through tyrosine phosphorylation of
      IkappaBalpha in Jurkat cells, whereas it induces an IKK-mediated IkappaBalpha
      phosphorylation on S32 and 36 in CEM and Jurkat JR cells. We showed that this
      H2O2-induced IKK activation in CEM and Jurkat JR cells is mediated by SH2
      containing inositol 5'-phosphatase 1 (SHIP-1), a lipid phosphatase that is absent
      in Jurkat cells. Indeed, the complementation of SHIP-1 in Jurkat cells made them
      shift to an IKK-dependent mechanism upon oxidative stress stimulation. We also
      showed that Jurkat cells expressing SHIP-1 are more resistant to H2O2-induced
      apoptosis than the parental cells, suggesting that SHIP-1 has an important role
      in leukemic cell responses to ROS in terms of signal transduction pathways and
      apoptosis resistance, which can be of interest in improving ROS-mediated
      chemotherapies.

PMID- 16619040
TI  - Deletion of the carcinoembryonic antigen-related cell adhesion molecule 1
      (Ceacam1) gene contributes to colon tumor progression in a murine model of
      carcinogenesis.
AB  - Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a
      glycoprotein that is part of the carcinoembryonic antigen and the immunoglobulin
      superfamilies. We have shown that it functions as a tumor suppressor and that
      this function depends upon the presence of the longer CEACAM1 cytoplasmic domain.
      In this report, we describe the generation of a Ceacam1-/- mouse. The Ceacam1-/-
      colon exhibits increased in vivo proliferation relative to the wild-type
      counterpart with a corresponding decreased expression of the p21(Cip1) and
      p27(Kip1) Cyclin D kinase inhibitors. The colonic villi undergo decreased
      apoptosis. Out of 35 litters of mice, no spontaneous tumors in any tissues
      normally expressing CEACAM1 were found over the lifespan of the animals,
      suggesting that CEACAM1 may not be involved in initiation of tumor development.
      However, when mice are treated with azoxymethane to induce colonic tumors, we
      find that Ceacam1-/- mice developed a significantly greater number of tumors than
      their littermate controls. Moreover, the tumor size was greater in the knockout
      mice relative to that in the wild-type mice. These results indicate that deletion
      of CEACAM1 favors progression of colon tumorigenesis.

PMID- 16619042
TI  - Apoptotic DNA fragmentation factor maintains chromosome stability in a P53
      independent manner.
AB  - DNA fragmentation factor (DFF)/caspase-activated DNase (CAD) is responsible for
      DNA fragmentation, a hallmark event during apoptosis. Although DNA fragmentation
      is an evolutionarily conserved process across species, its biological function is
      not clearly understood. In this study, we constructed cell lines expressing a
      mutant ICAD (inhibitor of CAD) protein that is resistant to caspase cleavage and
      therefore constantly binds to DFF/CAD and inhibits DNA fragmentation. We found
      that irradiation of these cells led to increased chromosome aberrations and
      aneuploidy when compared with their parental controls. The increased chromosome
      instability is observed irrespective of cellular P53 status, suggesting that the
      effect of DFF/CAD is independent of P53. Inhibition of apoptotic DNA
      fragmentation resulted in increased clonogenic survival of irradiated cells and a
      delay in removal of cells with DNA damages induced by radiation, an effect
      similar to that in cells with p53 mutations. Consistent with DFF/CAD's effect on
      clonogenic survival, tumors established from cells deficient in DNA fragmentation
      showed enhanced growth in nude mice. Therefore, our results suggest that DFF/CAD
      plays an important and P53-independent role in maintaining chromosome stability
      and suppressing tumor development.

PMID- 16619041
TI  - Interleukin-1 alpha mediates the growth proliferative effects of transforming
      growth factor-beta in p21 null MCF-10A human mammary epithelial cells.
AB  - Transforming growth factor-beta type 1 (TGF-beta) has been implicated as both a
      tumor suppressor and a tumor promoter in many solid epithelial cancers. We have
      previously demonstrated that the cyclin dependent kinase (CDK) inhibitor p21 acts
      as a molecular switch in determining a growth inhibitory versus growth
      proliferative response to TGF-beta in the spontaneously immortalized human
      mammary epithelial cell line MCF-10A. We now demonstrate that this proliferative
      effect of TGF-beta is mediated through the proinflammatory cytokine, interleukin
      1alpha (IL-1alpha). Using gene expression array analysis, we identified IL-1alpha
      as a cytokine specifically upregulated only in cells lacking p21 and only upon
      TGF-beta stimulation. Cell proliferation assays verified that recombinant IL
      1alpha was capable of inducing a growth proliferative response in p21 null MCF
      10A cells, while neutralizing antibodies against IL-1alpha prevented the growth
      proliferative effects of TGF-beta. Mechanistically, both the CDK and
      proliferating cell nuclear antigen (PCNA) inhibitory functions of p21 were
      responsible for preventing TGF-beta induced cell proliferation, but only PCNA
      inhibition by p21 regulated IL-1alpha gene expression. These studies demonstrate
      a novel role for IL-1alpha in mediating a proliferative response to TGF-beta
      signaling, and suggest that therapies directed against IL-1alpha could abate the
      growth proliferative effects of TGF-beta without compromising its tumor
      suppressive function.

PMID- 16619043
TI  - Chk1-dependent slowing of S-phase progression protects DT40 B-lymphoma cells
      against killing by the nucleoside analogue 5-fluorouracil.
AB  - Chk1 plays a crucial role in the DNA damage and replication checkpoints in
      vertebrates and may therefore be an important determinant of tumour cell
      responses to genotoxic anticancer drugs. To evaluate this concept we compared the
      effects of the nucleoside analogue 5-fluorouracil (5FU) on cell cycle progression
      and clonogenic survival in DT40 B-lymphoma cells with an isogenic mutant
      derivative in which Chk1 function was ablated by gene targeting. We show that 5FU
      activates Chk1 in wild-type DT40 cells and that 5FU-treated cells accumulate in
      the S phase of the cell cycle due to slowing of the overall rate of DNA
      replication. In marked contrast, Chk1-deficient DT40 cells fail to slow DNA
      replication upon initial exposure to 5FU, despite equivalent inhibition of the
      target enzyme thymidylate synthase, and instead accumulate progressively in the
      G1 phase of the following cell cycle. This G1 accumulation cannot be reversed
      rapidly by exogenous thymidine or removal of 5FU, and is associated with
      increased incorporation of 5FU into genomic DNA and severely diminished
      clonogenic survival. Taken together, these results demonstrate that a Chk1
      dependent replication checkpoint which slows S phase progression can protect
      tumour cells against the cytotoxic effects of 5FU.

PMID- 16619044
TI  - Stat3 contributes to keloid pathogenesis via promoting collagen production, cell
      proliferation and migration.
AB  - Keloids, partially considered as benign tumors, represent the most extreme
      example of cutaneous scarring that uniquely afflicts humans as a pathological
      response to wound healing. It is characterized by excessive deposition of
      collagen and other extracellular matrix components by dermal fibroblasts. Upon
      cutaneous injury, cocktails of chemokines, cytokines and growth factors are
      secreted temporally and spatially to direct appropriate responses from
      neutrophils, macrophages, keratinocytes and fibroblasts to facilitate normal
      wound healing. Signal transducer and activator of transcription 3 (Stat3) is an
      oncogene and a latent transcription factor activated by various cytokines and
      growth factors. We investigated the possible role of Stat3 in keloid scar
      pathogenesis by examining skin tissue and cultured fibroblasts from keloid
      scarred patients. We observed enhanced expression and phosphorylation of Stat3 in
      keloid scar tissue, and in cultured keloid fibroblasts (KFs) in vitro. Increased
      activation of Janus kinase (Jak)2, but not Jak1, was detected in KFs, and
      suppression of Jak2 by its inhibitor repressed Stat3 Y705 phosphorylation.
      Inhibition of Stat3 expression and phosphorylation by short interfering RNA or
      Cucurbitacin I resulted in the loss of collagen production, impaired
      proliferation and delayed cell migration in KFs. We show, for the first time, a
      role of Stat3 in keloid pathogenesis. Inhibitors of Stat3 may be useful
      therapeutic strategies for the prospective treatment of keloid scars.

PMID- 16619045
TI  - Expression of hTERT immortalises normal human urothelial cells without
      inactivation of the p16/Rb pathway.
AB  - The CDKN2A locus is frequently inactivated in urothelial cell carcinoma (UCC),
      yet how this alteration contributes to bladder tumorigenesis is not known.
      Although most UCC express telomerase, inactivation of the p16/Rb pathway is
      generally required for in vitro immortalisation. This and the involvement of p16
      in senescence of normal human urothelial cells (NHUC) suggest that CDKN2A
      deletion may aid bypass of senescence and allow immortalisation. CDKN2A encodes
      p16 and p14ARF and therefore inactivation of this locus can disrupt both the Rb
      and p53 tumour suppressor pathways. Retrovirus-mediated transduction was used to
      specifically modulate the p16/Rb and/or p53 tumour suppressor pathways in NHUC
      and to express human telomerase reverse transcriptase (hTERT). Expression of
      hTERT bypassed Rb and p53 pathway-dependent barriers to proliferation and
      immortalised NHUC. TERT-NHUC had normal karyotypes, were non-tumorigenic and
      unexpectedly retained CDKN2A. Thus, the phenotypic significance of inactivation
      of CDKN2A in UCC may not be solely related to bypass of senescence. Phenotypic
      assays in human urothelial cells have relied on cell strains derived from
      invasive tumours or NHUC immortalised by expression of SV40-large T. The
      production of genetically normal but immortal NHUC lines now provides a valuable
      platform for experiments to examine the timing and combination of events
      necessary for UCC tumorigenesis.

PMID- 16619046
TI  - Two patterns of chromosomal breakpoint locations on the immunoglobulin heavy
      chain locus in B-cell lymphomas with t(3;14)(q27;q32): relevance to histology.
AB  - The t(3;14)(q27;q32) is the most common translocation involving BCL6 in B-cell
      lymphoma. Although this translocation was predominantly associated with diffuse
      large B-cell lymphoma (DLBCL), recent studies have shown that it can also be
      found in follicular lymphomas (FL), often associated with a large cell component.
      To further investigate the relationship that might exist between this
      translocation and the phenotype of the tumors, we studied 34 lymphomas with a
      t(3;14)(q27;q32). Twenty cases were DLBCL, 14 FL and most cases, regardless of
      histology, were negative for the expression of CD10 (26/32, 81%). We identified
      the IGH switch region involved in the translocation for 32 cases. Our data
      indicate that in DLBCL most breakpoints involve the switch mu (17/19; 89%),
      whereas in FL most involve a switch gamma (9/13; 70%) (P=0.0016, Fisher's exact
      test). This correlation between the histology and the structure of the
      translocated allele suggests that the lymphomas with Smu and Sgamma
      translocations may originate from different cells, or that the substituted
      regulatory regions that come to deregulate BCL6 may affect the presentation of
      the disease.

PMID- 16619047
TI  - hTERT: a novel endogenous inhibitor of the mitochondrial cell death pathway.
AB  - hTERT is the catalytic subunit of the telomerase and is hence required for
      telomerase maintenance activity and cancer cell immortalization. Here, we show
      that acute hTERT depletion has no adverse effects on the viability or
      proliferation of cervical and colon carcinoma cell lines, as evaluated within 72
      h after transfection with hTERT-specific small interfering RNAs (siRNAs). Within
      the same time frame, hTERT depletion facilitated the induction of apoptotic cell
      death by cisplatin, etoposide, mitomycin C and reactive oxygen species, yet
      failed to sensitize cells to death induction via the CD95 death receptor.
      Experiments performed with p53 knockout cells or chemical p53 inhibitors revealed
      that p53 was not involved in the chemosensitizing effect of hTERT knockdown.
      However, the proapoptotic Bcl-2 family protein Bax was involved in cell death
      induction by hTERT siRNAs. Depletion of hTERT facilitated the conformational
      activation of Bax induced by genotoxic agents. Moreover, Bax knockout abolished
      the chemosensitizing effect of hTERT siRNAs. Inhibition of mitochondrial membrane
      permeabilization by overexpression of Bcl-2 or expression of the cytomegalovirus
      encoded protein vMIA (viral mitochondrial inhibitor of apoptosis), which acts as
      a specific Bax inhibitor, prevented the induction of cell death by the
      combination of hTERT depletion and chemotherapeutic agents. Altogether, our data
      indicate that hTERT inhibition may constitute a promising strategy for
      facilitating the induction of the mitochondrial pathway of apoptosis.

PMID- 16619048
TI  - Characterization of a recurrent translocation t(2;3)(p15-22;q26) occurring in
      acute myeloid leukaemia.
AB  - Six patients with de novo acute myeloid leukemia (AML) and a t(2;3)(p15-21;q26
      27) were identified among approximately 1000 cases enrolled in the GIMEMA trial.
      The t(2;3) was the sole anomaly in three patients, whereas in three cases
      monosomy 7, trisomy 15 and 22, and trisomy 14 represented additional aberrations.
      No cryptic chromosome deletions at 5q, 7q, 12p, and 20q were observed. One
      patient carried a FLT3 D835 mutation; FLT3 internal tandem duplication (ITD) was
      not detected in three patients tested. Characterization of the translocation
      breakpoints using a 3q26 BAC contig specific for the PRDM3 locus showed that the
      breakpoints were located 5' to EVIl as follows: within myelodysplatic syndrome
      (MDS) intron 1 (# 3), between MDS1 exons 2 and 3 in three patients (# 1, 2, 4)
      with a 170bp cryptic deletion distal to the breakpoint in one (# 2), and in a
      more centromeric position spanning from intron 2 to the 5' region of EVI1 (# 6,
      5). A set of 2p16-21 BAC probes showed that the breakpoints on chromosome 2p were
      located within BCL11A in two separate regions (# 1, 4 and # 2-5), within the
      thyroid adenoma-associated (THADA) gene (# 6) or distal to the ZFP36L2 locus (#
      3). Regulatory elements were present in proximity of these breakpoints. RACE PCR
      studies revealed a chimeric transcript in 1/6 patient analyzed, but no fusion
      protein. Quantitative PCR showed a 21-58-fold over-expression of the EVIl gene in
      all cases analyzed. The patients showed dysplasia of at least two myeloid cell
      lineages in all cases; they had a low-to-normal platelet count and displayed an
      immature CD34+ CD117+ immunophenotype. Despite intensive chemotherapy and a
      median age of 43 years (range 36-59), only two patients attained a short-lived
      response; one patient is alive with active disease at 12 months, five died at 4
      14 months. We arrived at the following conclusions: (a) the t(2;3) is a recurrent
      translocation having an approximate 0.5% incidence in adult AML; (b) breakpoints
      involve the 5' region of EVIl at 3q26, and the BCL11A, the THADA gene or other
      regions at 2p16.1-21; (c) cryptic deletions distal to the 3q26 breakpoint may
      occur in some cases; (d) the juxtaposition of the 5' region of EVIl with
      regulatory elements normally located on chromosome 2 brings about EVI1
      overexpression; (e) clinical outcome in these cases is severe.

PMID- 16619049
TI  - An integrated view of protein evolution.
AB  - Why do proteins evolve at different rates? Advances in systems biology and
      genomics have facilitated a move from studying individual proteins to
      characterizing global cellular factors. Systematic surveys indicate that protein
      evolution is not determined exclusively by selection on protein structure and
      function, but is also affected by the genomic position of the encoding genes,
      their expression patterns, their position in biological networks and possibly
      their robustness to mistranslation. Recent work has allowed insights into the
      relative importance of these factors. We discuss the status of a much-needed
      coherent view that integrates studies on protein evolution with biochemistry and
      functional and structural genomics.

PMID- 16619050
TI  - Organizing cell renewal in the intestine: stem cells, signals and combinatorial
      control.
AB  - The lining of the intestine is renewed at an extraordinary rate, outpacing all
      other tissues in the vertebrate body. The renewal process is neatly organized in
      space, so that the whole production line, from the ever-youthful stem cells to
      their dying, terminally differentiated progeny, is laid out to view in
      histological sections. A flurry of recent papers has clarified the key regulatory
      signals and brought us to the point where we can begin to give a coherent
      account, for at least one tissue, of how these signals collaborate to organize
      the architecture and behaviour of a stem-cell system.

PMID- 16619051
TI  - Mesoderm induction: from caps to chips.
AB  - Vertebrate mesoderm induction is one of the classical problems in developmental
      biology. Various developmental biology approaches, particularly in Xenopus and
      zebrafish, have identified many of the key factors that are involved in this
      process and have provided major insights into how these factors interact as part
      of a signalling and transcription-factor network. These data are beginning to be
      refined by high-throughput approaches such as microarray assays. Future
      challenges include understanding how the prospective mesodermal cells integrate
      the various signals they receive and how they resolve this information to
      regulate their morphogenetic behaviours and cell-fate decisions.

PMID- 16619052
TI  - Family-based designs in the age of large-scale gene-association studies.
AB  - Both population-based and family-based designs are commonly used in genetic
      association studies to locate genes that underlie complex diseases. The simplest
      version of the family-based design--the transmission disequilibrium test--is well
      known, but the numerous extensions that broaden its scope and power are less
      widely appreciated. Family-based designs have unique advantages over population
      based designs, as they are robust against population admixture and
      stratification, allow both linkage and association to be tested for and offer a
      solution to the problem of model building. Furthermore, the fact that family
      based designs contain both within- and between-family information has substantial
      benefits in terms of multiple-hypothesis testing, especially in the context of
      whole-genome association studies.

PMID- 16619053
TI  - Polymorphisms in the dopamine D4 receptor gene (DRD4) contribute to individual
      differences in human sexual behavior: desire, arousal and sexual function.
AB  - Although there is some evidence from twin studies that individual differences in
      sexual behavior are heritable, little is known about the specific molecular
      genetic design of human sexuality. Recently, a specific dopamine D4 receptor
      (DRD4) agonist was shown in rats to induce penile erection through a central
      mechanism. These findings prompted us to examine possible association between the
      well-characterized DRD4 gene and core phenotypes of human sexual behavior that
      included desire, arousal and function in a group of 148 nonclinical university
      students. We observed association between the exon 3 repeat region, and the C
      521T and C-616G promoter region SNPs, with scores on scales that measure human
      sexual behavior. The single most common DRD4 5-locus haplotype (19%) was
      significantly associated with Desire, Function and Arousal scores. The current
      results are consistent with animal studies that show a role for dopamine and
      specifically the DRD4 receptor in sexual behavior and suggest that one pathway by
      which individual variation in human desire, arousal and function are mediated is
      based on allelic variants coding for differences in DRD4 receptor gene expression
      and protein concentrations in key brain areas.

PMID- 16619054
TI  - Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood
      disorder-like phenotypes.
AB  - There is no established genetic model of bipolar disorder or major depression,
      which hampers research of these mood disorders. Although mood disorders are
      multifactorial diseases, they are sometimes manifested by one of pleiotropic
      effects of a single major gene defect. We focused on chronic progressive external
      ophthalmoplegia (CPEO), patients with which sometimes have comorbid mood
      disorders. Chronic progressive external ophthalmoplegia is a mitochondrial
      disease, which is accompanied by accumulation of mitochondrial DNA (mtDNA)
      deletions caused by mutations in nuclear-encoded genes such as POLG (mtDNA
      polymerase). We generated transgenic mice, in which mutant POLG was expressed in
      a neuron-specific manner. The mice showed forebrain-specific defects of mtDNA and
      had altered monoaminergic functions in the brain. The mutant mice exhibited
      characteristic behavioral phenotypes, a distorted day-night rhythm and a robust
      periodic activity pattern associated with estrous cycle. These abnormal behaviors
      resembling mood disorder were worsened by tricyclic antidepressant treatment and
      improved by lithium, a mood stabilizer. We also observed antidepressant-induced
      mania-like behavior and long-lasting irregularity of activity in some mutant
      animals. Our data suggest that accumulation of mtDNA defects in brain caused mood
      disorder-like mental symptoms with similar treatment responses to bipolar
      disorder. These findings are compatible with mitochondrial dysfunction hypothesis
      of bipolar disorder.

PMID- 16619055
TI  - Obesity indices and cardiovascular risk factors in Thai adults.
AB  - OBJECTIVE: To examine the relationship of body mass index (BMI), waist
      circumference (WC), waist-to-hip ratio (WHpR) and waist-to-height ratio (WHtR)
      with cardiovascular risk factors and diabetes in Thai population. DESIGN: A
      national cross-sectional survey of cardiovascular risk factors. SUBJECTS: Five
      thousand and three hundred five Thai adults aged > or =35 years. MEASUREMENTS:
      Body weight, height, waist and hip circumference and cardiovascular risk factors
      including blood pressure, total plasma cholesterol, high-density lipoprotein,
      triglyceride and fasting plasma glucose were measured. Age- and sex-specific
      means and prevalence of cardiovascular risk factors were calculated and compared
      among anthropometric measurements. RESULTS: There were increasing trends of
      severity of cardiovascular risk factors and prevalence of morbidity conditions
      across increasing levels of BMI, WC, WHpR and WHtR categories. For age group > or
      =65 years, WC, WHpR and WHtR provided more consistent association with
      cardiovascular risk factors than BMI. Area under the curve indicated that
      measurement of central obesity could predict cardiovascular risk better than BMI.
      The optimal cutoff points for anthropometric measurements were in line with the
      Asia-Pacific recommendation; however, similar cutoff point for men and women
      between 82 and 85 cm was observed. CONCLUSION: Central obesity indices were
      slightly better associated with cardiovascular risk factors compared to BMI in
      Thai adults aged > or =35 years.

PMID- 16619056
TI  - Oxyntomodulin increases energy expenditure in addition to decreasing energy
      intake in overweight and obese humans: a randomised controlled trial.
AB  - BACKGROUND: Oxyntomodulin has recently been found to decrease body-weight in
      obese humans and may be a potential anti-obesity therapy. OBJECTIVE: To determine
      whether oxyntomodulin alters energy expenditure, in addition to reducing energy
      intake, in 'free-living' overweight and obese volunteers. DESIGN: Randomized
      double-blind controlled cross-over trial. SETTING: Community and hospital-based.
      PARTICIPANTS: Fifteen healthy overweight and obese men and women (age: 23-49
      years, BMI: 25.1-39.0 kg/m(2)). All volunteers completed the study protocol.
      INTERVENTIONS: Four-day subcutaneous self-administration of pre-prandial
      oxyntomodulin, three times daily. Participants were advised to maintain their
      normal dietary and exercise regimen. MEASUREMENTS: (1) Energy expenditure,
      measured by indirect calorimetry and combined heart rate and movement monitoring;
      (2) energy intake, measured during a study meal. RESULTS: Oxyntomodulin
      administration reduced energy intake at the study meal by 128+/-29 kcal
      (P=0.0006) or 17.3+/-5.5% (P=0.0071), with no change in meal palatability.
      Oxyntomodulin did not alter resting energy expenditure; but increased activity
      related energy expenditure by 143+/-109 kcal/day or 26.2+/-9.9% (P=0.0221); total
      energy expenditure by 9.4+/-4.8% (P=0.0454) and physical activity level by 9.5+/
      4.6% (P=0.0495). A reduction in body weight of 0.5+/-0.2% was observed during the
      oxyntomodulin administration period (P=0.0232). CONCLUSION: Oxyntomodulin
      increases energy expenditure while reducing energy intake resulting in negative
      energy balance. This data supports the role of oxyntomodulin as a potential anti
      obesity therapy.

PMID- 16619058
TI  - [Ibsen, physicians and the Tidsskrift].

PMID- 16619057
TI  - Influence of obesity on accurate and rapid arm movement performed from a standing
      posture.
AB  - INTRODUCTION: Obesity yields a decreased postural stability. The potentially
      negative impact of obesity on the control of upper limb movements, however, has
      not been documented. This study sought to examine if obesity imposes an
      additional balance control constraint limiting the speed and accuracy with which
      an upper limb goal-directed movement performed from an upright standing position
      can be executed. METHOD: Eight healthy lean subjects (body mass index (BMI)
      between 20.9 and 25.0 kg/m(2)) and nine healthy obese subjects (BMI between 30.5
      and 48.6 kg/m(2)) pointed to a target located in front of them from an upright
      standing posture. The task was to aim at the target as fast and as precisely as
      possible after an auditory signal. The difficulty of the task was varied by using
      different target sizes (0.5, 1.0, 2.5 and 5.0 cm width). Hand movement time (MT)
      and velocity profiles were measured to quantify the aiming. Centre of pressure
      and segmental kinematics were analysed to document postural stability. RESULTS:
      When aiming, the forward centre of pressure (CP) displacement was greater for the
      obese group than for the normal BMI group (4.6 and 1.9 cm, respectively). For the
      obese group, a decrease in the target size was associated with an increase in
      backward CP displacement and CP peak speed whereas for the normal BMI group
      backward CP displacements and CP peak speed were about the same across all target
      sizes. Obese participants aimed at the target moving their whole body forward
      whereas the normal BMI subjects predominantly made an elbow extension and
      shoulder flexion. For both groups, MT increased with a decreasing target size.
      Compare to the normal BMI group, this effect was exacerbated for the obese group.
      For the two smallest targets, movements were on average 115 and 145 ms slower for
      the obese than for the normal BMI group suggesting that obesity added a balance
      constraint and limited the speed with which an accurate movement could be done.
      SUMMARY: Obesity, because of its effects on the control of balance, also imposes
      constraints on goal-directed movements. From a clinical perspective, obese
      individuals might be less efficient and more at risk of injuries than normal
      weight individuals in a large number of work tasks and daily activities requiring
      upper limb movements performed from an upright standing position.

PMID- 16619059
TI  - [Tularemia].

PMID- 16619060
TI  - [A medical ritual].

PMID- 16619061
TI  - [Doctors' use and assessment of a fee-for-service life-style advice scheme].
AB  - BACKGROUND: Fee-for-service life-style advice, a "green prescription" was
      introduced in Norway in 2003 as an alternative to the prescription of drugs to
      patients with moderate hypertension or risk of type 2 diabetes. The prescription
      includes an assessment of diet and/or physical activity, and an individual plan
      for change with systematic follow up from the GP. Material was provided by the
      Directorate of Health and Social Affairs, and a special fee of NOK 200 was
      established. The Research Institute of the Norwegian Medical Association has
      evaluated GPs' attitudes to and use of this scheme. MATERIAL AND METHODS: A
      representative sample of 1134 Norwegian GPs, of whom 59% responded. Ten of the
      respondents were also interviewed comprehensively over the telephone. RESULTS AND
      INTERPRETATION: Green prescriptions has low legitimacy among Norwegian GPs.
      Advise on lifestyle to patients with moderate hypertension or risk of type 2
      diabetes is already an integral and natural component of GP work and calls for no
      extra fee or bureaucratic procedures. There is a risk of medicalisation in that
      non-patients become patients. On the other hand, patients who already are on
      drugs, but who may be able to reduce or eliminate these if they change their
      lifestyle, are not included in the scheme. Further development of the concept
      should to a larger degree include collaboration with the GPs.

PMID- 16619062
TI  - [Gestational diabetes in women from South Asia].
AB  - BACKGROUND: The number of patients with diabetes is growing worldwide. In
      particular this increase, most pronounced for type 2 diabetes, affects South
      Asians. In Norway pregnant women originating from this region are more prone to
      gestational diabetes than ethnic Norwegians. More knowledge is needed to prevent
      and treat this disease effectively. Here we give a brief overview of the
      epidemiology and risk factors associated with gestational diabetes. MATERIALS AND
      METHODS: Information related to gestational diabetes was obtained from various
      databases, including PubMed, HighWire and Ovid, in addition to our own
      experience. RESULTS AND INTERPRETATION: Some methodological aspects preclude a
      definite assessment of the true extent of gestational diabetes nationally as well
      as internationally. About 0.01 3% of Caucasian pregnancies are affected while the
      corresponding number among South-Asian women is 5 to 10 times higher. Most
      studies identify obesity as an important risk factor. Generally, advice on diet
      and physical activity can prevent diabetes. Similar interventions might also be
      useful among the increasing population of immigrant fertile women in Norway.

PMID- 16619063
TI  - [Rhythms, depressions and light].
AB  - Many aspects of life in plants, animals and humans are controlled by light.
      Endogenous, so-called circadian rhythms in the body deviate from the exact 24
      hour day and have typically a period of around 25.5 hours in man. Normally these
      rhythms adapt to the external 24-hour day-and night changes but under constant
      conditions the rhythms can free run. Many studies show how important the
      interplay between light and the circadian rhythms are for man as well as for
      other organisms. The control of these rhythms by light is mediated via the retina
      and the melatonin system in man. The adaptation of the rhythms is very important
      in shift work, in rapid jet lag travels over time zones, etc. Organisms often use
      the circadian rhythm to determine the length of day and of night, a feature that
      has given rise to the term biological clocks. A biological clock provides
      possibilities to determine the proper time for physiological processes to start
      in plants and animals (flowering, hibernation etc). The importance of light and
      circadian rhythms for seasonal affective disorders and manic-depressive disorders
      is also discussed. For several organisms one has now been able to specify genes
      that determine the period of the clocks. The rhythmic physiologic processes, the
      light reactions and the general importance of light for rhythms and for man are
      now studied at the molecular level.

PMID- 16619064
TI  - [The photobiology of vitamin D--a topic of renewed focus].
AB  - The sun is our most important source of vitamin D. Exposure to solaria, in sub
      erythemogenic doses, also gives large amounts of this vitamin. The ultraviolet
      radiation in these sources converts 7-dihydrocholesterol to previtamin D3 in the
      skin. Furthermore, heat isomerization to vitamin D3 takes place, then transport
      to the liver and hydroxylation to calcidiol, which is transported to the kidneys
      and hydroxylated to the active hormone calcitriol. The vitamin D3 status of the
      body is supposed to be reliably imaged by calcidiol measurements. Calcidiol
      levels above 12.5 nmol/l prevent rickets and osteomalacia, but optimal levels are
      probably higher, in the range 100-250 nmol/l. A daily food intake of 100-200
      microg vitamin D3 (50-100 g cod-liver oil), or a weekly exposure to two minimal
      erythemal doses of ultraviolet radiation (20 to 40 minutes whole body exposure to
      midday midsummer sun in Oslo, Norway), will give this level. An adequate supply
      of vitamin D3 seems to reduce the incidence rates or improve the prognosis of
      several cancer forms, including prostate, breast and colon cancer, as well as of
      lymphomas. Several other diseases are related to a low vitamin D3 status: heart
      diseases, multiple sclerosis, diabetes, and arthritis. The action mechanisms of
      vitamin D are thought to be mainly related to its known cell-differentiating and
      immuno-modulating effects. Even though most of the 250 annual death cases from
      skin cancer in Norway are caused by sun exposure, we should, in view of the
      health effects of ultraviolet radiation, consider modifying our restrictive
      attitude towards sun exposure and use of solaria.

PMID- 16619065
TI  - [Tularaemia as a differential diagnosis in tumour colli].
AB  - BACKGROUND: Tularaemia is a bacterial zoonosis caused by the bacterium
      Francisella tularensis. Different species of rodents and small mammals are the
      main reservoir; the transmission of disease is caused by direct contact with
      diseased animals, via insect vectors, or by ingestion of contaminated food and
      water. The disease is known to cause a complex clinical presentation in which
      head and neck manifestations are common. It occurs at a low annual rate in the
      northern and middle regions of Norway, but in recent years there have been
      several reported cases also in the southern parts of the country. The incidence
      of tularaemia is much higher in Sweden compared to Norway; the reason remains
      obscure. MATERIAL AND METHODS: In this paper we report two admitted cases in
      which fever and a solitary neck mass were the predominant clinical findings. We
      review the number of cases reported to the Norwegian Institute of Public Health
      from 1976 to 2002, with particular emphasis on the role of tularaemia in the
      context of a neck tumour and oropharyngeal symptoms. RESULTS AND INTERPRETATION:
      The suspicion of tularaemia should be raised in patients with a solitary neck
      mass of presumed infectious aetiology, in particular when administration of beta
      lactam antibiotics has failed. The diagnosis is usually dependent on serological
      evidence of F. tularensis infection. Recently, PCR techniques have been developed
      that facilitate rapid detection of F. tularensis in clinical specimens.

PMID- 16619066
TI  - [Increasing antibiotic resistance in urinary tract infections].
AB  - BACKGROUND: There is increasing focus on the development of bacterial antibiotic
      resistance. MATERIALS AND METHODS: We conducted a retrospective study of urine
      samples from patients resident in a Norwegian county, comparing 9121 samples
      culture-positive in 2003-04 with 28 066 samples in 1997-99. Determination of
      resistance was done with the MAST automatic multipoint inoculator system.
      RESULTS: Escherichia coli was found in 68% and 56% of out-patient and in-patient
      isolates respectively. Significant declines in mecillinam sensitivity (from 96%
      to 94%), nitrofurantoin sensitivity (from 97% to 95%) and sulfonamide sensitivity
      (from 73% to 71%) in in-patient E. coli isolates were found. In out-patients we
      found significant reductions in sensitivity to ampicillin (from 78% to 76%) and
      trimethoprim (from 83% to 82%). For urinary tract infection isolates as a whole,
      the greatest sensitivity was observed for nitrofurantoin: 85% in in-patient
      isolates and 75% in out-patient isolates, but there was a significant decline in
      resistance to several antibiotics. INTERPRETATION: Increasing antibiotic
      resistance may be related to increasing antibiotic use. Mecillinam and
      nitrofurantoin may be considered first-choice preparations as E. coli is the
      dominant etiological agent and shows the greatest sensitivity to these two
      antibiotics.

PMID- 16619067
TI  - [Unified management in Norwegian hospitals--still controversial?].
AB  - BACKGROUND: The Norwegian parliament's decision to establish unified management
      on all hospitals units was accompanied by strong public debate. The arguments
      focused especially on the decision that other than doctors could fill the top
      managerial position at the department level. We have studied the selection of
      managers, the prevalence and content of disagreements and conflicts, and how the
      departments handled the conflicts. MATERIAL AND METHODS: We have used three data
      sets: a survey of the top managements at all hospitals, interviews with 28
      managers, and a survey of a sample of managers at the department level. RESULTS
      AND INTERPRETATIONS: In 2004, about 67% of the managers were doctors, 28% were
      nurses and 5% had other professional backgrounds. Managers educated as nurses
      were most prevalent in psychiatric wards and in emergency medicine. About half of
      the hospitals and departments had experienced conflicts when implementing the
      reform. Confusion about medical responsibility and resistance towards the manager
      not being a doctor seemed to be most common. With some exception, the conflicts
      have calmed down, probably because of some clarification from the Ministry of
      Health about the managers' medical responsibility; also, departments with
      managers who not are doctors have established a division of labour that satisfy
      the doctors in the department.

PMID- 16619068
TI  - [Clinical use of long-acting insulin analogs].

PMID- 16619069
TI  - [Right to necessary health care--our priority law].

PMID- 16619070
TI  - [Does increased productivity result in more health?].

PMID- 16619071
TI  - [Retired researchers--a research resource?].

PMID- 16619072
TI  - [Legal rights of the dying].

PMID- 16619073
TI  - [Generic name or brand name?].

PMID- 16619074
TI  - [Health legislation and medical ethics].

PMID- 16619078
TI  - [The seroxat issue--a reply].

PMID- 16619080
TI  - [Vision correction in firemen and smoke divers].

PMID- 16619087
TI  - Preschool language development among children of adolescent mothers.
AB  - This longitudinal study examined a comprehensive set of predictors of preschool
      language performance in a sample of children of adolescent mothers. Six domains
      of risk (low maternal verbal ability, intergenerational risk, contextual risk,
      relational risk, home environmental risk, and child characteristics) for poor
      preschool language development, measured throughout early childhood, were
      examined in a sample of 154 children born to adolescent mothers. Logistic
      regression revealed that having a poor language-learning home environment was
      associated with children's low language scores even after accounting for mothers'
      below-average verbal ability. More importantly, however, was the exploration of
      the 'dual risk' hypothesis that evaluated the effects of combined risk factors.
      Being reared by a mother with low verbal ability amplified the risk of a poor
      quality home linguistic environment, whereas having a poor home linguistic
      environment did not adversely affect the language development of children with
      mothers of average verbal ability. Implications for intervention are discussed
      with regard to specificity of intervention efforts within subpopulations of risk
      identified in this paper.

PMID- 16619089
TI  - It's time for evidence.

PMID- 16619088
TI  - Efficient Algorithms for Determining 3-D Bi-Plane Imaging Geometry.
AB  - Biplane projection imaging is one of the primary methods for imaging and
      visualizing the cardiovascular system in medicine. A key problem in such a
      technique is to determine the imaging geometry (i.e., the relative rotation and
      translation) of two projections so that the interested 3-D structures can be
      accurately reconstructed. Based on interesting observations and efficient
      geometric techniques, we present in this paper new algorithmic solutions for this
      problem. Comparing with existing optimization-based approaches, our techniques
      yield better accuracy, have bounded execution time, and thus are more suitable
      for on-line applications. Our techniques can easily detect outliers to further
      improve the accuracy.

PMID- 16619090
TI  - Core temperature and percentage of dehydration in professional football linemen
      and backs during preseason practices.
AB  - CONTEXT: Thermal responses of average-sized male subjects (mass of approximately
      70 kg) may not accurately reflect the rate of heat storage in larger athletes
      with greater muscle mass. OBJECTIVE: To determine if core temperature (T(c)) is
      different in National Football League linemen and backs and if T(c) is related to
      percentage of dehydration or sweat rate. DESIGN: We measured T(c) and sweat rate
      in professional football players during preseason twice-daily practices. SETTING:
      Preseason training camp. PATIENTS OR OTHER PARTICIPANTS: Eight linemen (age =
      26.6 +/- 2.1 years, height = 191.8 +/- 4.5 cm, mass = 134.8 +/- 10.7 kg, body
      surface area = 2.61 +/- 0.12 m2) and 6 backs (age = 27.0 +/- 4.2 years, height =
      185.0 +/- 6.3 cm, mass = 95.6 +/- 11.1 kg, body surface area = 2.19 +/- 0.16 m2).
      MAIN OUTCOME MEASURE(S): We measured T(c) using ingestible sensors. Resting T(c)
      was recorded in the mornings of data collection with players dressed in shorts
      and then every 15 minutes during 2-hour practices in full pads or shells. Mass
      was recorded before and after practices for determining the percentage of
      dehydration. In 8 of the 14 subjects (4 linemen, 4 backs), sweat rate was
      calculated using the change in mass adjusted for fluid intake and urine
      production. RESULTS: Height, mass, and body surface area were greater in linemen
      than in backs. We noted a linear trend over time for T(c) in both groups. Maximal
      T(c) was higher in linemen (38.65 +/- 0.48 degrees C) than in backs (38.44 +/-
      0.32 degrees C), but linemen were less dehydrated than backs (-0.94 +/- 0.6%
      versus -1.3 +/- 0.7%). Sweat rate was 2.11 +/- 0.77 L/h and correlated
      significantly with body surface area (r = 0.77, P < .05). Maximal T(c) was not
      correlated with either percentage of dehydration or sweat rate. CONCLUSIONS:
      Maximal T(c) was not associated with percentage of dehydration or sweat rate.
      Linemen were less dehydrated but demonstrated higher T(c) than backs during
      practice. Maximal T(c) was generally achieved during live scrimmaging.

PMID- 16619091
TI  - Creatine use and exercise heat tolerance in dehydrated men.
AB  - CONTEXT: Creatine monohydrate (CrM) use is highly prevalent in team sports (eg,
      football, lacrosse, ice hockey) and by athletes at the high school, college,
      professional, and recreational levels. Concerns have been raised about whether
      creatine use is associated with increased cramping, muscle injury, heat
      intolerance, and risk of dehydration. OBJECTIVE: To assess whether 1 week of CrM
      supplementation would compromise hydration status, alter thermoregulation, or
      increase the incidence of symptoms of heat illness in dehydrated men performing
      prolonged exercise in the heat. DESIGN: Double-blind, randomized, crossover
      design. SETTING: Human Performance Laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Twelve active males, age = 22 +/- 1 year, height = 180 +/- 3 cm, mass = 78.8 +/-
      1.2 kg, body fat = 9 +/- 1%, V(O2)peak = 50.9 +/- 1 ml.kg(-1).min(-1).
      INTERVENTION(S): Subjects consumed 21.6 g.d(-1) of CrM or placebo for 7 days,
      underwent 48 +/- 10 days of washout between treatments, and then crossed over to
      the alternate treatment in the creatine group. On day 7 of each treatment,
      subjects lost 2% body mass by exercising in 33.5 degrees C and then completed an
      80-minute exercise heat-tolerance test (33.5 degrees C +/- 0.5 degrees C,
      relative humidity = 41 +/- 12%). The test consisted of four 20-minute sequences
      of 4 minutes of rest, alternating a 3-minute walk and 1-minute high-intensity run
      3 times, and walking for 4 minutes. MAIN OUTCOME MEASURES: Thermoregulatory,
      cardiorespiratory, metabolic, urinary, and perceptual responses. RESULTS: On day
      7, body mass had increased 0.88 kg. No interaction or treatment differences for
      placebo versus CrM during the exercise heat-tolerance test were noted in
      thermoregulatory (rectal temperature, 39.3 +/- 0.4 degrees C versus 39.4 +/- 0.4
      degrees C) cardiorespiratory (Vo(2), 21.4 +/- 2.7 versus 20.0 +/- 1.8 ml.kg(
      1).min(-1); heart rate, 192 +/- 10 versus 192 +/- 11 beats.min(-1); mean arterial
      pressure, 90 +/- 9 versus 88 +/- 5 mm Hg), metabolic (lactate, 6.7 +/- 2.7 versus
      7.0 +/- 3.0 mmol.L(-1)), perceptual thirst (thirst, 7 +/- 1 versus 7 +/- 1;
      thermal sensation, 8 +/- 2 versus 8 +/- 1; rating of perceived exertion, 17 +/- 3
      versus 17 +/- 2), plasma glucose (0-20 minutes of exercise heat-tolerance, 6.5 +/
      1.2 versus 6.8 +/- 0.8 mmol.L(-1)), plasma (297 +/- 5 versus 300 +/- 4 mOsm.kg(
      1)) and urine (792 +/- 117 versus 651 +/- 134 mOsm.kg(-1)), urine specific
      gravity (1.025 +/- 0.003 versus 1.030 +/- 0.005) and urine color (7 +/- 1 versus
      6 +/- 1) measures were increased during CrM. Environmental Symptoms Questionnaire
      scores were similar between treatments. The levels of dehydration incurred during
      dehydration and the exercise heat-tolerance test were similar and led to similar
      cumulative body mass losses (-4.09 +/- 0.53 versus -4.38 +/- 0.58% body mass).
      CONCLUSIONS: Short-term CrM supplementation did not increase the incidence of
      symptoms or compromise hydration status or thermoregulation in dehydrated,
      trained men exercising in the heat.

PMID- 16619092
TI  - Creatine supplementation and anterior compartment pressure during exercise in the
      heat in dehydrated men.
AB  - CONTEXT: Theoretically, the risk of compartment syndrome is increased during
      creatine monohydrate (CrM) supplementation because of intracellular fluid
      retention in muscle cells and the overall increased size of the muscle tissue.
      Whether this change in intracellular fluid is associated with an increase in
      anterior compartment pressure in the lower leg when subjects are under thermal
      stress is unknown. OBJECTIVE: To assess the influence of CrM on the resting and
      postexercise anterior compartment pressure of the lower leg in mildly to
      moderately dehydrated males exercising in the heat. DESIGN: Double-blind,
      randomized, crossover design. SETTING: Human Performance Laboratory. PATIENTS OR
      OTHER PARTICIPANTS: Eleven well-trained, non- heat-acclimated, healthy males (age
      = 22 +/- 2 years, height = 181.1 +/- 7 cm, mass = 78.4 +/- 4.2 kg, V(O2)max =
      50.5 +/- 3.4 mL.kg(-1).min(-1)). INTERVENTION(S): Subjects were supplemented with
      21.6 g/d of CrM or placebo for 7 days. On day 7, they performed 2 hours of
      submaximal exercise, alternating 30 minutes of walking with 30 minutes of cycling
      in the heat, resulting in approximately 2% dehydration. This was followed by an
      80-minute heat tolerance test (temperature = 33.5 +/- 0.5 degrees C, humidity =
      41.0 +/- 12%), which included 12 repetitions of a 3-minute walk (pace = 4.0 +/-
      0.1 miles/h, intensity = 37.1 +/- 6.1% V(O2)max) alternating with a 1-minute,
      high-intensity run (pace = 11.8 +/- 0.4 miles/h, intensity = 115.0 +/- 5.6%
      V(O2)max), resulting in an additional 2% decrease in body weight. MAIN OUTCOME
      MEASURES: Before supplementation and on day 7 of supplementation, anterior
      compartment pressure was measured at rest, after dehydration, and at 1, 3, 5, 10,
      15, and 60 minutes after the heat tolerance test. Analysis of variance with
      repeated measures was calculated to compare differences within the trials and
      time points and to identify any interaction between trial and time. RESULTS: The
      CrM intake was associated with an increase in body weight (P < .05). A moderate
      effect size was noted for compartment pressures between the trials for the
      differences between predehydration and postdehydration (eta2 = 0.414). This
      effect diminished substantially by 3 minutes after the heat tolerance test.
      Compared with the placebo trial, the change in anterior compartment pressure from
      rest to dehydration was greater, as was the change from rest to 1 minute after
      the heat tolerance test (P < .05) during the CrM trial. CONCLUSIONS: A 7-day
      loading dose of CrM increased anterior compartment pressures after dehydration
      and immediately after the heat tolerance tests, but the changes did not induce
      symptoms and the pressure changes were transient.

PMID- 16619093
TI  - Dehydration and symptoms of delayed-onset muscle soreness in normothermic men.
AB  - CONTEXT: A dehydrated individual who performs eccentric exercise may exacerbate
      skeletal muscle damage, leading to structural, contractile, and enzymatic protein
      denaturation, in addition to the myofiber and connective damage resulting from
      the eccentric muscle tension. OBJECTIVE: To identify the effects of dehydration
      on 5 physiologic characteristics of delayed-onset muscle soreness (DOMS) in
      normothermic men after an eccentric exercise perturbation. DESIGN: Randomized
      group test-retest design. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS:
      Ten healthy male volunteers randomly assigned to either a euhydration (age = 26.2
      +/- 4.9 years, height = 174.1 +/- 6.0 cm, mass = 86.5 +/- 15.3 kg) or dehydration
      (age = 25.8 +/- 2.2 years, height = 177.2 +/- 3.1 cm, mass = 84.4 +/- 3.8 kg)
      group. INTERVENTION(S): Subjects performed treadmill walking for 45 minutes in
      either a thermoneutral (euhydration) or a hot, humid (dehydration) environment.
      After a rest period to allow for return to the normothermic condition, DOMS was
      induced with a 45-minute downhill run. MAIN OUTCOME MEASURES: We assessed 5
      physiologic characteristics of DOMS before and at intervals after the eccentric
      exercise. The characteristics were perceived pain of the bilateral quadriceps and
      overall body, bilateral punctate tenderness of the superficial quadriceps
      muscles, bilateral knee-flexion passive range of motion, bilateral thigh
      circumference, and bilateral isometric quadriceps muscle strength.
      Thermoregulatory and cardiovascular measures were obtained to monitor
      participants' heat load during exercise. RESULTS: The experimental protocol
      produced a 0.9% increase in body mass of the euhydration group and a significant
      2.7% decrease in body mass of the dehydration group. The downhill-running
      exercise perturbation induced DOMS in both the euhydrated and dehydrated
      participants, based on increased bilateral quadriceps and overall body perceived
      pain and punctate tenderness of the bilateral vastus medialis muscle. The signs
      and symptoms of DOMS after an eccentric exercise perturbation were not
      exacerbated by moderate dehydration of 2.7% body mass after rest and return to
      the normothermic condition. CONCLUSIONS: Significantly dehydrated participants
      who rested and returned to a normothermic condition did not experience increased
      characteristics of DOMS.

PMID- 16619094
TI  - A comparison of bioelectrical impedance and skinfold measurements in determining
      minimum wrestling weights in high school wrestlers.
AB  - CONTEXT: Whether bioelectrical impedance and skinfold analysis can be used
      interchangeably to establish minimal wrestling weights (MWWs) is unknown. Using
      both methods in a particular program may result in the misclassification of some
      athletes. OBJECTIVE: To compare the MWW calculated from skinfold measurements
      with those derived from 5 bioelectrical impedance equations and determine if the
      2 methods could be used interchangeably for high school wrestlers. DESIGN:
      Repeated measurements were obtained using bioelectrical impedance and skinfold
      analysis to determine MWWs. Data were collected during the preseason. SETTING:
      High school. PATIENTS OR OTHER PARTICIPANTS: Two hundred eight wrestlers (151
      males, 57 females), aged 13 to 18 years. MAIN OUTCOME MEASURE(S): The
      bioelectrical impedance analysis was conducted with the MWW protocol administered
      annually by certified athletic trainers. The resistance and reactance were used
      in 5 equations to investigate the level of agreement between bioelectrical
      impedance and skinfold analysis for determining MWW. The MWWs were based on a
      minimum body fat of 7.0% for males and 14.0% for females. RESULTS: When comparing
      bioelectrical impedance and skinfold analysis, we found prediction error ranged
      from 1.51 to 2.34 kg for males and 0.27 to 9.16 kg for females. CONCLUSIONS: To
      protect the health of the athletes and maintain competitive equity, a single
      method should be used to determine MWWs. Bioelectrical impedance and skinfold
      analysis cannot be used interchangeably to determine MWWs.

PMID- 16619095
TI  - Glenohumeral joint laxity and stiffness in the functional throwing position of
      high school baseball pitchers.
AB  - CONTEXT: Repetitive overhead throwing has been theorized to result in chronic
      adaptations to the capsuloligamentous restraints of the glenohumeral joint.
      OBJECTIVE: To compare glenohumeral joint laxity and stiffness between the
      throwing and nonthrowing shoulders of high school baseball pitchers. DESIGN:
      Repeated measures. SETTING: High school athletic training facilities. PATIENTS OR
      OTHER PARTICIPANTS: Twenty-two asymptomatic high school baseball pitchers (age =
      16.50 +/- 0.74 years, height = 178.51 +/- 7.66 cm, mass = 75.43 +/- 13.24 kg)
      from a sample of convenience. MAIN OUTCOMES MEASURE(S): We used computerized
      stress arthrometry to measure glenohumeral joint laxity and stiffness. Anterior
      glenohumeral joint laxity and stiffness measures were obtained with the shoulder
      in 90 degrees of abduction and both neutral rotation and 90 degrees of external
      rotation. Posterior laxity and stiffness measures were obtained with the shoulder
      in 90 degrees of abduction and neutral rotation. RESULTS: No clinically
      significant differences were found for glenohumeral laxity or stiffness between
      sides. However, a statistically significant main effect for position was present
      for both laxity and stiffness. Anterior glenohumeral joint laxity in the 90
      degrees external rotation position was significantly decreased and stiffness was
      increased in this position compared with the anterior at neutral and posterior at
      neutral positions. CONCLUSIONS: Glenohumeral joint laxity decreases and stiffness
      increases in the functional throwing position of 90 degrees of abduction and 90
      degrees of external rotation. No clinically significant side-to-side differences
      or directional differences were found in high school baseball pitchers.

PMID- 16619096
TI  - The influence of external loads on movement precision during active shoulder
      internal rotation movements as measured by 3 indices of accuracy.
AB  - CONTEXT: Using constant, variable, and absolute error to measure movement
      accuracy might provide a more complete description of joint position sense than
      any of these values alone. OBJECTIVE: To determine the effect of loaded movements
      and type of feedback on shoulder joint position sense and movement velocity.
      DESIGN: Applied study with repeated measures comparing type of feedback and the
      presence of a load. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty
      healthy subjects (age = 27.2 +/- 3.3 years, height = 173.2 +/- 18.1 cm, mass =
      70.8 +/- 14.5 kg) were seated with their arms in a custom shoulder wheel.
      INTERVENTION(S): Subjects internally rotated 27 degrees in the plane of the
      scapula, with either visual feedback provided by a video monitor or
      proprioceptive feedback provided by prior passive positioning, to a target at 48
      degrees of external rotation. Subjects performed the internal rotation movements
      with video feedback and proprioceptive feedback and with and without load (5% of
      body weight). MAIN OUTCOME MEASURE(S): High-speed motion analysis recorded peak
      rotational velocity and accuracy. Constant, variable, and absolute error for
      joint position sense was calculated from the final position. RESULTS: Unloaded
      movements demonstrated significantly greater variable error than for loaded
      movements (2.0 +/- 0.7 degrees and 1.5 +/- 0.4 degrees, respectively) (P < .05),
      but there were no differences in constant or absolute error. Peak velocity was
      greater for movements with proprioceptive feedback (45.6 +/- 2.9 degrees/s) than
      visual feedback (39.1 +/- 2.1 degrees/s) and for unloaded (47.8 +/- 3.6
      degrees/s) than loaded (36.9 +/- 1.0 degrees/s) movements (P < .05). CONCLUSIONS:
      Shoulder joint position sense demonstrated greater variable error unloaded versus
      loaded movements. Both visual feedback and additional loads decreased peak
      rotational velocity.

PMID- 16619097
TI  - Differences in neuromuscular strategies between landing and cutting tasks in
      female basketball and soccer athletes.
AB  - CONTEXT: High school female athletes are most likely to sustain a serious knee
      injury during soccer or basketball, 2 sports that often involve a rapid
      deceleration before a change of direction or while landing from a jump.
      OBJECTIVE: To determine if female high school basketball and soccer players show
      neuromuscular differences during landing and cutting tasks and to examine
      neuromuscular differences between tasks and between dominant and nondominant
      sides. DESIGN: A 3-way mixed factorial design investigating the effects of sport
      (basketball, soccer), task (jumping, cutting), and side (dominant, nondominant).
      SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty high school female
      athletes who listed either basketball or soccer as their only sport of
      participation (basketball: n = 15, age = 15.1 +/- 1.7 years, experience = 6.9 +/-
      2.2 years, height = 165.3 +/- 7.9 cm, mass = 61.8 +/- 9.3 kg; soccer: n = 15, age
      = 14.8 +/- 0.8 years, experience = 8.8 +/- 2.5 years, height = 161.8 +/- 4.1 cm,
      mass = 54.6 +/- 7.6 kg). MAIN OUTCOME MEASURE(S): Ground reaction forces, stance
      time, valgus angles, and valgus moments were assessed during (1) a drop vertical
      jump with an immediate maximal vertical jump and (2) an immediate side-step cut
      at a 45 degrees angle. RESULTS: Basketball athletes had greater ground reaction
      forces (P < .001) and decreased stance time (P < .001) during the drop vertical
      jump, whereas soccer players had greater ground reaction forces (P <.001) and
      decreased stance time (P < .001) during the cut. Subjects in both sports had
      greater valgus angles (initial contact and maximum, P = .02 and P = .012,
      respectively) during cutting than during the drop vertical jump. Greater valgus
      moments (P = .006) were noted on the dominant side during cutting. CONCLUSIONS:
      Our subjects demonstrated differences in ground reaction forces and stance times
      during 2 movements associated with noncontact anterior cruciate ligament
      injuries. Knee valgus moment and angle were significantly influenced by the type
      of movement performed. Sport-specific neuromuscular training may be warranted,
      with basketball players focusing on jumping and landing and soccer players
      focusing on unanticipated cutting maneuvers.

PMID- 16619098
TI  - Ipsilateral hip abductor weakness after inversion ankle sprain.
AB  - CONTEXT: Hip stability and strength are important for proper gait mechanics and
      foot position during heel strike. OBJECTIVE: To determine the relationships
      between hip muscle strength and chronic ankle sprains and hip muscle strength and
      ankle range of motion. DESIGN: Ex post facto design with the uninvolved limb
      serving as the control. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A
      total of 23 subjects with unilateral chronic ankle sprain were recruited.
      Subjects had at least 2 ipsilateral ankle sprains and were bearing full weight,
      with the most recent injury occurring at least 3 months earlier. They were not
      undergoing formal or informal rehabilitation at the time of the study. MAIN
      OUTCOME MEASURE(S): We obtained goniometric measurements for all planes of motion
      at the ankle. Handheld dynamometry was used to assess the strength of the hip
      abductor and hip extensor muscles in both limbs. RESULTS: Hip abductor muscle
      strength and plantar flexion were significantly less on the involved side than
      the uninvolved side (P < .001 in each case). Strength of the involved hip
      abductor and hip extensor muscles was significantly correlated (r = 0.539, P <
      .01). No significant difference was noted in hip extensor muscle strength between
      sides (P = .19). CONCLUSIONS: Our subjects with unilateral chronic ankle sprains
      had weaker hip abduction strength and less plantar-flexion range of motion on the
      involved sides. Clinicians should consider exercises to increase hip abduction
      strength when developing rehabilitation programs for patients with ankle sprains.

PMID- 16619099
TI  - Reduced quadriceps activation after lumbar paraspinal fatiguing exercise.
AB  - CONTEXT: Although poor paraspinal muscle endurance has been associated with less
      quadriceps activation (QA) in persons with a history of low back pain, no authors
      have addressed the acute neuromuscular response after lumbar paraspinal fatiguing
      exercise. OBJECTIVE: To compare QA after lumbar paraspinal fatiguing exercise in
      healthy individuals and those with a history of low back pain. DESIGN: A 2 x 4
      repeated-measures, time-series design. SETTING: Exercise and Sport Injury
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: Sixteen volunteers participated (9
      males, 7 females; 8 controls and 8 with a history of low back pain; age = 24.1 +/
      3.1 years, height = 173.4 +/- 7.1 cm, mass = 72.4 +/- 12.1 kg). INTERVENTION(S):
      Subjects performed 3 sets of isometric lumbar paraspinal fatiguing muscle
      contractions. Exercise sets continued until the desired shift in lumbar
      paraspinal electromyographic median power frequency was observed. Baseline QA was
      compared with QA after each exercise set. MAIN OUTCOME MEASURE(S): An electric
      burst was superimposed while subjects performed a maximal quadriceps contraction.
      We used the central activation ratio to calculate QA = (F(MVIC)/[F(MVIC) +
      F(Burst)])* 100, where F = force and MVIC = maximal voluntary isometric
      contractions. Quadriceps electromyographic activity was collected at the same
      time as QA measurements to permit calculation of median frequency during MVIC.
      RESULTS: Average QA decreased from baseline (87.4% +/- 8.2%) after the first
      (84.5% +/- 10.5%), second (81.4% +/- 11.0%), and third (78.2% +/- 12.7%)
      fatiguing exercise sets. On average, the group with a history of low back pain
      showed significantly more QA than controls. No significant change in quadriceps
      median frequency was noted during the quadriceps MVICs. CONCLUSIONS: The
      quadriceps muscle group was inhibited after lumbar paraspinal fatiguing exercise
      in the absence of quadriceps fatigue. This effect may be different for people
      with a history of low back pain compared with healthy controls.

PMID- 16619100
TI  - Physiologic considerations of therapeutic slideboard rehabilitation with an
      external loading device.
AB  - CONTEXT: Slideboard exercise is consistent with the American College of Sports
      Medicine guidelines for exercise intensity of 55% to 90% of maximal heart rate or
      40% to 85% of maximal oxygen uptake. OBJECTIVE: To determine if slideboard
      exercise while in a leg harness increases the metabolic and cardiorespiratory
      demands. DESIGN: Repeated-measures design. SETTING: Athletic Training Research
      Laboratory. PATIENTS OR OTHER PARTICIPANTS: Sixteen volunteers from the
      university community. INTERVENTION(S): Subjects performed 2 graded slideboard
      exercise tests with and without the leg harness, each 2-minute stage ranging from
      46 to 90 slides per minute. MAIN OUTCOME MEASURE(S): We measured maximal oxygen
      uptake, heart rate, blood lactate, respiratory exchange ratio, ratings of
      perceived exertion, and total time to exhaustion during each session. RESULTS:
      Significant decreases in maximal oxygen uptake and blood lactate were observed
      when the leg harness was used. CONCLUSIONS: Performance was hindered when
      subjects wore the leg harness during the slideboard exercise.

PMID- 16619101
TI  - Reliability of first ray position and mobility measurements in experienced and
      inexperienced examiners.
AB  - CONTEXT: Neither reliability nor validity data exist for the Root method of
      clinically assessing first ray position or mobility by experienced and
      inexperienced examiners. OBJECTIVE: To determine intrarater and interrater
      reliability for first ray position and mobility measurements in experienced and
      inexperienced examiners. DESIGN: Single-blind prospective reliability study.
      SETTING: Physical therapy clinic. PATIENTS OR OTHER PARTICIPANTS: Four examiners,
      2 experienced and 2 inexperienced, obtained first ray position and mobility
      measurements. Both feet of 36 subjects (14 males, 22 females) were measured.
      INTERVENTION(S): Each examiner evaluated first ray position and mobility for each
      of the subjects' feet on 2 separate occasions using the manual assessment
      techniques described by Root. MAIN OUTCOME MEASURE(S): First ray position
      (normal, plantar flexed, dorsiflexed) and mobility (normal, hypermobile,
      hypomobile) decisions were made. RESULTS: We calculated kappa correlation
      coefficients for intrarater and interrater reliability. For position, intrarater
      and interrater reliability ranged from .03 to .27 for all examiners, experienced
      and inexperienced. For mobility, intrarater and interrater reliability ranged
      from .02 to .26 for experienced, inexperienced, and experienced/inexperienced.
      The percentage agreement (P(O)) values for all examiners were less than 58%. For
      individual values for position, intrarater and interrater reliability ranged from
      .00 to .26. For individual values for mobility, intrarater and interrater
      reliability ranged from .00 to .26. The P(O) values for all examiners were less
      than 50%. CONCLUSIONS: Clinical experience was not associated with higher kappa
      coefficients or P(O) values when examiners assessed first ray position or
      mobility. Clinicians should acknowledge the poor reliability of first ray
      measurements, especially when making treatment decisions. Finally, a validity
      study to compare the Root techniques with a gold standard is warranted.

PMID- 16619102
TI  - Peer-assisted learning in the athletic training clinical setting.
AB  - CONTEXT: Athletic training educators often anecdotally suggest that athletic
      training students enhance their learning by teaching their peers. However, peer
      assisted learning (PAL) has not been examined within athletic training education
      in order to provide evidence for its current use or as a pedagogic tool.
      OBJECTIVE: To describe the prevalence of PAL in athletic training clinical
      education and to identify students' perceptions of PAL. DESIGN: Descriptive.
      SETTING: "The Athletic Training Student Seminar" at the National Athletic
      Trainers' Association 2002 Annual Meeting and Clinical Symposia. PATIENTS OR
      OTHER PARTICIPANTS: A convenience sample of 138 entry-level male and female
      athletic training students. MAIN OUTCOME MEASURE(S): Students' perceptions
      regarding the prevalence and benefits of and preferences for PAL were measured
      using the Athletic Training Peer-Assisted Learning Assessment Survey. The Survey
      is a self-report tool with 4 items regarding the prevalence of PAL and 7 items
      regarding perceived benefits and preferences. RESULTS: A total of 66% of
      participants practiced a moderate to large amount of their clinical skills with
      other athletic training students. Sixty percent of students reported feeling less
      anxious when performing clinical skills on patients in front of other athletic
      training students than in front of their clinical instructors. Chi-square
      analysis revealed that 91% of students enrolled in Commission on Accreditation of
      Allied Health Education Programs-accredited athletic training education programs
      learned a minimal to small amount of clinical skills from their peers compared
      with 65% of students in Joint Review Committee on Educational Programs in
      Athletic Training-candidacy schools (chi2(3) = 14.57, P < .01). Multiple analysis
      of variance revealed significant interactions between sex and academic level on
      several items regarding benefits and preferences. CONCLUSIONS: According to
      athletic training students, PAL is occurring in the athletic training clinical
      setting. Entry-level students are utilizing their peers as resources for
      practicing clinical skills and report benefiting from the collaboration.
      Educators should consider deliberately integrating PAL into athletic training
      education programs to enhance student learning and collaboration.

PMID- 16619103
TI  - Stylistic learning differences between undergraduate athletic training students
      and educators: Gregorc mind styles.
AB  - CONTEXT: Learning theory and pedagogic research are unfamiliar to many educators
      trained in the sciences. Athletic training educators must learn to appreciate the
      theoretic and practical value of pedagogic research, including learning styles.
      OBJECTIVE: To extend the learning styles research in athletic training by
      introducing the Mind Styles model and Gregorc Style Delineator instrument to
      investigate students' and program directors' baseline style preferences and to
      study the effects of sex, education level, and academic role on mean composite
      Gregorc Style Delineator scores. DESIGN: Correlational research design. SETTING:
      Instruments were mailed to program directors and administered in classroom
      settings. PATIENTS OR OTHER PARTICIPANTS: Ten of 10 athletic training programs
      accredited by the Commission on Accreditation of Allied Health Education Programs
      formed sample 1, with 200 undergraduate athletic training students (68 men, 132
      women, age = 20.12 +/- 2.02 years). A total of 43 program directors (22 men, 21
      women, age = 40.05 +/- 9.30 years) created sample 2. MAIN OUTCOME MEASURE(S): We
      used the Gregorc Style Delineator to measure participants' perceptual and
      ordering abilities, combining them in a quaternary design to create mean
      composite scores for the Concrete Sequential (CS), Abstract Sequential (AS),
      Abstract Random (AR), and Concrete Random (CR) Mind Styles subscales. We also
      noted each subject's sex, education level, and academic role. RESULTS: We
      obtained a response rate of 100% of undergraduates and 43% of program directors.
      The CS style was preferred by 44.5% (n = 89) of students and 58.1% (n = 25) of
      program directors. Program directors preferred the CS style more (P < .001) and
      the AS and AR styles less (P < .001) than predicted by chi(2) testing. Students
      preferred the CS style more (P < .001) and the AS style less (P < .001) than
      expected also. Men students preferred the AS style more (P < .01) and the AR
      style less (P < .01) than women students. Students by chi2 testing were also less
      likely to prefer the CS style (P < .01) and more likely to prefer the AR style (P
      < .001) than program directors. No significant main effect was noted for
      education level (P = .310) or the interaction (P = .108). CONCLUSIONS: Our
      findings add 2 unique elements to the athletic training literature by extending
      the investigation of styles to an original model (Mind Styles) and the effect of
      academic role on style. Program directors should strongly consider sex and
      academic role style differences when designing and implementing pedagogic
      methods.

PMID- 16619104
TI  - Does McKenzie therapy improve outcomes for back pain?
AB  - CLINICAL QUESTION: What is the clinical evidence base for McKenzie therapy in
      management of back pain? DATA SOURCES: Studies were identified using a computer
      based literature search of 7 databases: MEDLINE, EMBASE, DARE, CINAHL, PEDro, the
      Cochrane Register of Clinical Trials (CENTRAL), and the Cochrane Database of
      Systematic Reviews. Search terms included McKenzie therapy, McKenzie treatment,
      and McKenzie method. Studies published before September 2003 were eligible. STUDY
      SELECTION: To be included in the review, each study had to fulfill the following
      criteria: (1) the study was a randomized or quasi-randomized controlled trial,
      (2) the subjects' primary complaint was nonspecific low back pain or neck pain
      with or without radiation to the extremities, (3) the authors investigated the
      efficacy of the McKenzie method/McKenzie treatment in comparison with no
      treatment, sham treatment, or another treatment, (4) individualized patient
      treatment and treatment were specified according to McKenzie principles, and (5)
      the authors reported at least one of the outcome measures of pain, disability,
      quality of life, work status, global perceived effect, medication use, medical
      visits, or recurrence. Studies were included with no language restriction and
      with subjects of all age groups, of either sex, and with any duration of
      symptoms. Studies were excluded if subjects had any of the following spinal
      conditions: cauda equina syndrome, cord compression, infection, fracture,
      neoplasm, inflammatory disease, pregnancy, any form of headache, whiplash
      associated disorders, vertigo/dizziness, or vertebrobasilar insufficiency. DATA
      EXTRACTION: Data were independently extracted from each study by 2 investigators
      using a standardized data extraction form. The standardized data extraction form
      and experience level of the investigators were not included in the review. In
      studies with more than 2 treatment groups, the treatment contrast of more
      relevance to current Australian physiotherapy was selected. Data were also
      extracted for short-, intermediate-, and long-term follow-up based on the
      criteria suggested by the Cochrane Back Review Group. Short-term follow-up was
      defined as less than 3 months from onset of treatment. Intermediate-term follow
      up was defined as at least 3 months and less than 12 months from onset of
      treatment. Long-term follow-up was defined as equal to or greater than 12 months.
      All eligible studies were rated for methodologic quality using the PEDro scale.
      The PEDro scale is a checklist that examines the "believability and the
      interpretability of trial quality."(1) The 11-item checklist yields a maximum
      score of 10 if all criteria are satisfied. The first item on the scale
      (Eligibility Criteria) is not scored. The PEDro scores were extracted from the
      PEDro database. If a study had not been entered into the database and scored, it
      was reviewed and scored by an experienced PEDro rater. MAIN RESULTS: Normalized
      data for pain and disability were given possible total scores of 100. The
      article's scores on the PEDro scale were average, ranging from 4 to 8 of 10. The
      most common flaw in the methods, which occurred in all 6 studies, was the failure
      to blind both the patient and therapist. Four of the 6 did not blind the
      researcher interpreting the data. For both pain and disability at short-term (<3
      months) follow-up, individual study results for low back pain favored McKenzie
      therapy compared with the following: nonsteroidal anti-inflammatory drugs,
      educational booklet, back massage with back care advice, strength training with
      therapist supervision, spinal mobilization, or general mobility exercises. Trends
      favored McKenzie therapy at intermediate-term (3-12 months) follow-up for pain
      and disability, as well as work absences. The McKenzie treatment group in the
      cervical spine study had less pain and disability at both short- and intermediate
      term follow-up than did the exercise group, although the effect sizes were small.
      The same McKenzie treatment group tended to have fewer health care contacts in
      the ensuing 12 months than the comparison exercise group. The results suggest
      that McKenzie therapy provides a reduction in short-term pain (mean reduction of
      8.6 on a 100-point scale) compared with the therapies mentioned above. A second
      (sensitivity) analysis was conducted to include data from 3 studies that were
      initially excluded because of lack of individualized treatment. The sensitivity
      analysis was used to determine if the exclusion of these studies would
      significantly alter the conclusion of the review. Instead, the sensitivity
      analysis strengthened the evidence supporting the notion that McKenzie therapy is
      more effective in short-term pain relief than other therapies (reduction of 11.4
      on a 100-point scale). CONCLUSIONS: This review provides evidence that McKenzie
      therapy results in a decrease in short-term (<3 months) pain and disability for
      low back pain patients compared with other standard treatments, such as
      nonsteroidal anti-inflammatory drugs, educational booklet, back massage with back
      care advice, strength training with therapist supervision, and spinal
      mobilization. No statistical differences were found between McKenzie therapy and
      other therapies at intermediate-term (3-12 months) follow-up. Data are
      insufficient on long-term (>12 months) outcomes or outcomes other than pain and
      disability (eg, quality of life). To date, no authors have compared McKenzie
      therapy with placebo or no treatment. Also, few data are available on the
      McKenzie method and its effect on neck pain. Future researchers should focus on
      these issues.

PMID- 16619105
TI  - Accuracy of 3 diagnostic tests for anterior cruciate ligament tears.
AB  - CLINICAL QUESTION: In patients presenting with possible rupture of the anterior
      cruciate ligament (ACL), which diagnostic test can provide an accurate diagnosis
      during the physical examination? DATA SOURCES: Two reviewers searched MEDLINE
      (1966 to February 14, 2003) and EMBASE (1980 to February 14, 2003). Articles
      written in English, French, German, or Dutch were included. The key search terms
      were knee injuries, knee joint, and knee. These terms were combined with the
      headings joint instability and anterior cruciate ligament, as well as the text
      words laxity, instability, cruciate, and effusion. The results of these searches
      were combined with the subject headings sensitivity and specificity, physical
      examination, and not (animal not [human and animal]). Additional text words
      searched were sensitivit*, specificit*, false positive, false negative, accuracy,
      screening, physical examination, and clinical examination. The reference lists of
      included articles were examined. STUDY SELECTION: Inclusion criteria consisted of
      (1) investigation of at least one physical diagnostic test for assessment of ACL
      ruptures in the knee and (2) the use of a reference standard of arthrotomy,
      arthroscopy, or magnetic resonance imaging. DATA EXTRACTION: Two independent
      reviewers extracted data from each included study. The methodologic quality of
      each test was assessed and recorded on a checklist for the screening of
      diagnostic tests (www.cochrane.de/cochrane/sadtdoc1.htm). The 3 diagnostic tests
      validated in this review were the pivot shift test, the anterior drawer test, and
      the Lachman test. A summary receiver operating characteristic curve was performed
      for each test, and the sensitivity, specificity, and predictive values were
      reported. MAIN RESULTS: The search strategy produced 1090 potentially eligible
      studies, of which 17 studies were selected. One study was included via reference
      list examination and 2 reports referred to the same study. Thus, 17 studies met
      the inclusion criteria and were used for this review. For the included studies,
      the sample size ranged from 32 to 300 patients. As for the age of the subjects,
      the authors of 4 studies failed to report it. Thus, the average age of patients
      across 13 of the 17 studies was 28.6 years. Authors of all studies failed to
      measure the clinical test and reference standard separately and with blinding. In
      addition, all but two studies had a significant degree of verification bias.
      Arthrotomy was the lone reference standard in 4 studies whereas
      arthrotomy/arthroscopy was the reference standard in 5 studies. Arthroscopy alone
      was the reference standard in 6 studies where only 2 studies used MRI as the
      reference standard. Authors of 8 studies examined the anterior drawer test and
      reported sensitivity values ranging from 0.18-0.92 and specificity values ranging
      from 0.78-0.98. When pooled together using the bivariate random effects model
      (BREM), the sensitivity value of the 8 studies was 0.2 and the specificity value
      was 0.88. Authors of 9 studies examined the Lachman test and reported sensitivity
      values ranging from 0.63-0.93 and specificity values ranging from 0.55-0.99.
      Pooled together using the BREM, the sensitivity value was 0.86 and the
      specificity value was 0.91. Lastly, authors of 6 studies examined the pivot shift
      test and reported sensitivity values ranging from 0.18-0.48 and specificity
      values ranging from 0.97-0.99. Data for the pivot shift test could not be pooled
      using the BREM because of the low number of available studies. Predictive values
      were reported graphically, with the pivot shift test having the highest positive
      predictive value and the Lachman test having the best negative predictive value.
      CONCLUSIONS: Based on predictive value statistics, it can be concluded that
      during the physical examination, a positive result for the pivot shift test is
      the best for ruling in an ACL rupture, whereas a negative result to the Lachman
      test is the best for ruling out an ACL rupture. It can also be concluded that,
      solely using sensitivity and specificity values, the Lachman test is a better
      overall test at both ruling in and ruling out ACL ruptures. The anterior drawer
      test appears to be inconclusive for drawing strong conclusions either way.

PMID- 16619106
TI  - Activation of ERK and suppression of calcineurin are interacting mechanisms of
      cardioprotection afforded by delta-opioid receptor activation.
AB  - The aim of this study was to examine possible interactions of ERK and calcineurin
      in cardioprotection afforded by delta-opioid receptor stimulation. Infarction was
      induced in rat hearts by 20-min coronary occlusion and reperfusion. Tissue ERK
      level and calcienurin activity were determined by immunoblotting and an assay
      using a phosphopeptide substrate, respectively. Administration of a delta-opioid
      receptor agonist, D-Ala2-D-Leu5-enkephalin (DADLE, 1 mg/kg), before ischemia
      increased the phospho-ERK levels during ischemia and reduced infarct size (as
      percentage of risk area, %IS/AR) from 47.7 +/- 2.3% to 23.2 +/- 2.5%. This
      protection was abolished by 10 mg/kg of natrindole hydrochloride (NTI), a delta
      opioid receptor antagonist. PD98059, a MEK1/2 inhibitor, abolished both ERK1/2
      activation and infarct size limitation by DADLE. Calcineurin inhibitors,
      cyclosporine-A (5 mg/kg) and FK506 (3.5 mg/kg), reduced %IS/AR (27.4 +/- 4.4% and
      29.9 +/- 3.4%, respectively). The protective effects of these calcineurin
      inhibitors were inhibited by PD98059, and the combination of DADLE with
      cyclosporine-A or FK506 did not afford further cardioprotection. DADLE
      significantly suppressed myocardial calcineurin activity, and this effect was
      inhibited by NTI. Suppression of calcineurin activity by FK506 was associated
      with modest activation of ERK1/2. These results suggest that suppression of
      calcineurin and activation of ERK1/2 are interacting mechanisms involved in
      cardioprotection by delta-opioid receptor activation.

PMID- 16619107
TI  - Contextual effects in school-based violence prevention programs: a conceptual
      framework and empirical review.
AB  - This paper reviews the theoretical and practical importance of studying
      contextual factors in school-based violence prevention programs and provides a
      framework for evaluating factors at the classroom, school, and community/district
      level. Sixty-two published papers describing 38 different programs were reviewed;
      of these 16 were identified that reported data on contextual effects or discussed
      possible contextual effects on the intervention. The small number of studies
      precludes definitive conclusions regarding contextual effects in school-based
      violence prevention programs, but suggests (a) some evidence for contextual
      effects on program outcomes, and (b) interdependence of context and
      implementation factors in influencing outcomes.Editors' Strategic Implications:
      This review suggests that contextual effects are important to school violence
      prevention, as context can influence outcomes directly and through interactions
      with implementation factors. Consequently, characteristics of the classroom,
      school, and community contexts should be considered by practitioners when
      implementing prevention programs and measured by researchers studying the
      processes and outcomes of these programs.

PMID- 16619108
TI  - The current role of ACE-inhibitors for secondary prevention in cardiovascular
      disease; from pathogenesis to clinical practice.

PMID- 16619112
TI  - Synthesis of 99mTc-HYNIC-interleukin-12, a new specific radiopharmaceutical for
      imaging T lymphocytes.
AB  - PURPOSE: Few radiopharmaceuticals have been described for the study of lymphocyte
      trafficking despite its high clinical relevance. The main difficulty resides in
      the identification of a suitable highly specific probe to target these cells.
      Interleukin-12 (IL12) is a heterodimeric cytokine which plays a key role in the
      development of Th(1) lymphocytes. The aims of the present study were to label
      IL12 with (99m)Tc, to evaluate its ability to bind to activated T lymphocytes in
      vitro and to study its biodistribution in normal mice and mice affected by
      autoimmune colitis. METHODS: IL12 was derivatised with HYNIC-NHS and labelled
      with( 99m)Tc. An in vitro binding assay was performed on KIT225 cells, an IL12
      receptor-positive cell line. (99m)Tc-IL12 biodistribution in normal mice was
      studied. Targeting experiments were performed in Balb/c mice injected with KIT225
      cells and in mice with chemically induced chronic colitis. RESULTS: (99m)Tc-IL12
      labelling efficiency ranged between 75% and 85%. Saturation binding analysis
      revealed a K (d) of 2.09 nM. Results of biodistribution studies showed a
      predominant hepatic route of excretion. A significant degree of uptake in the
      spleen and thymus was also observed. In mice injected with KIT225 cells, (99m)Tc
      IL12-specific uptake in these cells increased over time. (99m)Tc-IL12 also
      accumulated significantly in bowel of mice affected by TNBS-induced colitis
      showing T lymphocyte infiltration at histology, while accumulation in colon from
      control animals was negligible. CONCLUSION: We conclude that this radiolabelled
      cytokine is a suitable candidate for specific in vivo imaging of T lymphocytes: a
      step forward in molecular imaging of immune-mediated processes.

PMID- 16619113
TI  - Efficient genetic transformation system for the ochratoxigenic fungus Aspergillus
      carbonarius.
AB  - Aspergillus carbonarius is a potent ochratoxin A producer that has been found in
      products such as grapes, coffee, spices, and cocoa. Ochratoxin A has nephrotoxic
      effect, and it has been classified as a possible carcinogenic substance for
      humans. Here we describe for the first time a transformation system for A.
      carbonarius, providing an important step towards its genetic manipulation.
      Conidia were transformed to acquire hygromycin B resistance using the AGL-1
      strain of Agrobacterium tumefaciens. Genetic transformation was evaluated growing
      A. tumefaciens cells in induction medium containing or not acetosyringone prior
      to co-cultivation. The mean transforming efficiencies in IM+AS and IM-AS
      conditions were 62.2 and 44.5 transformants per 10(5) conidia, respectively. The
      hph gene was random integrated into the genome of A. carbonarius. Fungal
      sequences flanking the insertion site could be amplified by TAIL-PCR.

PMID- 16619114
TI  - Bacterial cell shape-dependent inflammatory response in mammary epithelial cells.
AB  - An in vitro co-culture model of SCp2 mammary epithelial cells and Escherichia
      coli strains was established in bacterial non-CO(2) incubators. Co-culturing SCp2
      cells with either the rod-shaped W3110 or spherical-shaped GC7378Tn10 strains of
      Escherichia coli led to an increase in interleukin-6 (IL-6) levels by SCp2 cells
      after 9 h. At a ratio of 1:100 (epithelial:bacterial), the rod-shaped W3110
      strain induced almost double the amount of IL-6 induced by the spherical-shaped
      GC7378Tn10 strain. The effect of Escherichia coli morphology (rod versus
      spherical) on IL-6 production by SCp2 cells was further investigated by shifting
      GC7378Tn10 morphology to rod through introducing the pbpA gene by transduction
      and transformation. In both approaches, the generated rod strains elicited higher
      IL-6 levels in SCp2 cells compared to the spherical ones at 1:50 and 1:100 ratios
      (epithelial:bacterial). Our findings demonstrate the significance of cell shape
      in bacterial-host interactions with potential implications in bacterial
      pathogenesis in general.

PMID- 16619115
TI  - Abdominoperineal excision with partial anterior en bloc resection in multimodal
      management of low rectal cancer: a strategy to reduce local recurrence.
AB  - PURPOSE: Total mesorectal excision is the gold standard in the performance of an
      abdominoperineal resection but little has changed in the way the perineal
      operation is performed. A frequent problem is anterior dissection. The aim of
      this study was to present the results of abdominoperineal resection using
      selected partial anterior en bloc resection to reduce recurrence. METHODS: The
      data were population-based and prospectively registered. Two experienced surgeons
      performed the operations. In selected cases, depending on clinical and magnetic
      resonance imaging findings, parts of the vagina or prostate close to the tumor
      were resected. All specimens were examined according to Quirke. RESULTS: Sixty
      three patients underwent abdominoperineal resection with total mesorectal
      excision; 56 received preoperative radiotherapy. The tumors involved the anterior
      bowel wall in 40 cases and in 23 (58 percent) of them, en bloc resections were
      performed. The distance from the tumor to the conventional resection margin
      (without en bloc resection) was 0 mm in ten cases. The median follow-up period
      was 37 months. So far, one (1.7 percent) local recurrence has been detected in 58
      (92 percent) curative and indeterminate cases. The cancer-specific five-year
      survival in these cases was 87 percent (Kaplan-Meier). CONCLUSION: A multimodal
      management regimen in patients with low rectal cancer, including preoperative
      radiotherapy and abdominoperineal resection with a high frequency of partial en
      bloc resection of the vagina or prostate, resulted in excellent local control and
      survival. In some male patients, excenteration with urinary stoma can be avoided.

PMID- 16619117
TI  - Lactate increase and oxygen desaturation in mitochondrial disorders--evaluation
      of two diagnostic screening protocols.
AB  - BACKGROUND: Mitochondrial disorders are characterized by an accumulation of
      lactate and an insufficient oxygen extraction from blood during exercise.
      Therefore, both parameters (lactate and oxygen saturation) can be used as
      screening tests in mitochondrial disorders. However, conflicting results
      regarding sensitivities and specifities of both tests have been reported. METHOD:
      We examined 27 patients with genetically defined mitochondrial disorders (single
      deletions n = 15, multiple deletions n = 5, A3243G mutation n = 7), patients with
      other neuromuscular disorders, and healthy controls. In the first test subjects
      performed intermittent isometric handgrip exercise (0.5 Hz) at 80% (3 minutes)
      and 30% (3 and 15 minutes) of maximal contraction force (MCF). Oxygen saturation
      and partial pressure in cubital venous blood from the exercising arm were
      measured. In the second test subjects underwent cycle ergometry at 30 W for 15
      minutes. Venous lactate at rest, during and 15 minutes postexercise was
      determined. RESULT: Both tests showed specificities of 92-96%. Sensitivities for
      changes of venous oxygen partial pressure and oxygen saturation ranged from 21
      26% at 80% MCF for 3 minutes to 47-58% at 30% MCF for 15 minutes. Sensitivities
      for venous resting, peak, and post-exercise lactate was 33%, 58%, and 67%,
      respectively. The degree of deoxygenation, however,was independent of the
      intensity and duration of the applied forces. Oxygen desaturation and lactate
      increase in patients with mitochondrial disorders were not different in patients
      with and without clinical symptoms of myopathy. There were significant
      correlations between the heteroplasmy and both the degree of oxygen desaturation
      and lactate increase in patients with single deletions. In patients who performed
      both protocols (n = 16) a combination of both tests increased sensitivity up to
      87%. CONCLUSION: Oxygen desaturation in forearm exercise tests and lactate
      increase in cycle ergometry tests show a high specifity but only moderate
      sensitivity. Combination of the two screening test clearly increases the
      sensitivity.

PMID- 16619116
TI  - Regional cerebral perfusion abnormalities in developmental language disorder.
      Statistical parametric mapping analysis.
AB  - OBJECTIVE: A voxel based investigation of cerebral blood flow was conducted to
      identify brain functional differences during resting state between children with
      developmental language disorder (DLD) and normal controls. METHOD: Using DSM-IV
      criteria, we selected 21 children with DLD. All children were examined by
      technetium-99m-HMPAO Brain SPECT. Using SPM analyses, we compared the SPECT
      images of children with DLD and those of 17 control subjects on a voxel by voxel
      basis using ANCOVA covarying for age. RESULTS: Reduced cerebral blood flow in the
      right putamen,the right inferior parietal cortex, and the left globus pallidus
      were found in children with DLD versus the controls. However, no area of
      increased cerebral blood flow was observed in children with DLD compared to the
      controls. CONCLUSION: Though results should be interpreted cautiously, this study
      confirms the presence of functional defects in the basal ganglia and the inferior
      parietal lobe during the resting state of the brains of children with DLD. It
      also gives further evidence for functional deficits in basal ganglia as an
      important factor in the etiology of DLD.

PMID- 16619118
TI  - Prior therapy with antiplatelet agents is not associated with outcome in patients
      with acute ischemic stroke/TIA.
AB  - BACKGROUND AND PURPOSE: It is unclear whether prior therapy with antiplatelet
      agents (APA) is associated with a better outcome in patients with acute ischemic
      cerebrovascular events. METHODS: Within a multi-center cross-sectional study,
      nested in a cohort we analyzed the relation between prior therapy with APA and
      stroke severity in 1643 patients with acute ischemic stroke or TIA. Clinical
      severity of the vascular event was evaluated by the National Institutes of Health
      Stroke Scale on admission (NIHSS1) and after 1 week (NIHSS2). By means of
      analysis of variance we analyzed a possible association of APA with stroke
      severity and interactions regarding stroke severity between APA and other
      clinical measures. RESULTS: 475 patients (29 %) received aspirin prior to the
      cerebrovascular event, 51 patients (3 %) ticlopidine or clopidogrel and 26
      patients (1.6%) aspirin combined with extended release dipyridamole. 66% (1091)
      of patients did not take any antiplatelet medication. Neither the NIHSS1 nor the
      NIHSS2 nor the change of stroke severity between these time points (NIHSS1-
      NIHSS2) was associated with prior APA medication. We did not find significant
      interactions between APA use and clinical measures regarding stroke severity.
      CONCLUSIONS: Our results do not indicate that prior therapy with APA is
      associated with a better outcome in acute ischemic cerebrovascular events. There
      were no interactions found with other features that were associated with stroke
      severity.

PMID- 16619119
TI  - Insular infarcts and electrocardiographic changes at admission: results of the
      PRognostic of Insular CErebral infarctS Study (PRINCESS).
AB  - BACKGROUND AND PURPOSE: Previous studies showed that insular strokes are
      associated with electrocardiographic (ECG) changes. However, they did not take
      into account the 1(st) ECG recorded at admission, but continuous ECG recorded up
      to 72 hours after onset. Whether these changes are the consequence of the
      infarct, or are associated with a cardiac source of cerebral ischemia, remains
      unsettled. If ECG changes are the consequence of insular infarcts, they should
      not have developed by the time of admission. The aim of this study was to test
      the hypothesis that ECG changes in patients with insular infarcts are not present
      at admission. METHODS: We recruited consecutive patients admitted within 48 hours
      (median 3 hours) after the onset of symptoms of acute hemispheric cerebral
      ischemia. We compared ECG variables between patients with and without insular
      infarcts, and with left and right insular infarcts. RESULTS: The study population
      consisted of 208 patients (94 men; median age: 69 years). Seventy patients had a
      recent insular infarct (right in 33). ECG variables did not significantly differ
      between patients with and without insular infarcts, and with left and right
      insular infarcts. These results were not explained by a lack of statistical power
      (1-beta >/= 0.90). CONCLUSION: The lack of statistical link between insular
      infarcts and ECG changes at admission, suggests that ECG changes are not
      associated with the cause of insular infarcts, but are their consequence.

PMID- 16619120
TI  - Estimates of the walking distance in multiple sclerosis patients and their effect
      on the EDSS.

PMID- 16619121
TI  - Change in artistic expression related to subthalamic stimulation.

PMID- 16619122
TI  - Genetic heterogeneity in 30 German patients with oculopharyngeal muscular
      dystrophy.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is due to short elongations of a
      polyalanine tract in the poly(A) binding protein nuclear 1 (PABPN1) gene.
      Originally GCG expansions in which (GCG)(6) is extended to (GCG)(7-13) were
      found. Subsequently five further genotypes with additional GCA- and GCG
      trinucleotides were identified in single OPMD patients. This indicated larger
      genetic heterogeneity and showed that unequal crossing-over and not replication
      slippage must be the underlying mechanism of elongation.We performed sequencing
      of the PABPN1 gene in 30 German OPDM index patients to determine the exact
      genotype. The original GCG expansion ranging from (GCG)(8) to (GCG)(11) was found
      in 22 patients. In 8 patients, however, three different elongated alleles other
      than classical (GCG)(7-13) were observed. Two of these genotypes had already been
      identified in Japanese patients. One genotype was recently identified showing
      (GCG)(6) followed by inserted (GCA)(3)GCG in four unrelated patients. This study
      further supports the theory of unequal crossing over as the molecular mechanism
      leading to elongation. It shows that other genotypes than classical (GCG)(7-13)
      are rather common in German OPMD patients. The data imply that there is no single
      founder effect in German OPMD patients.

PMID- 16619123
TI  - Functional response to active and passive ankle movements with clinical
      correlations in patients with primary progressive multiple sclerosis.
AB  - Patients with multiple sclerosis (MS) activate a more diffuse cortical network
      than do healthy subjects when they perform motor tasks. This brain functional
      reorganisation might contribute to the limiting of disability, but it is unclear
      whether there is a loss of regional activation in more advanced disease. The aim
      of this study was to assess whether functional reorganisation diminishes in more
      disabled patients with primary progressive (PP) MS. The differences in the fMRI
      response to active and passive movements of the dominant ankle of 13 patients and
      16 controls were assessed. The relationships between functional activation and
      disability and brain lesion load and atrophy were investigated.Patients showed
      greater fMRI activation than controls with passive movements in the superior
      temporal gyrus, rolandic operculum, and putamen. The fMRI response to active and
      passive movements in the ipsilateral inferior frontal gyrus was lower in patients
      with greater disability and greater brain T2 lesion load, respectively.
      Furthermore, the fMRI activation with active movements in the contralateral
      cerebellum was lower in patients with worse mobility. The increased activity with
      passive movements in regions that participate in sensori-motor integration, such
      as the putamen, reflects true functional reorganisation, since passive movements
      induce brain activation through sensory afferents only. The inverse correlation
      between the fMRI response in regions that are associated with motor control, and
      clinical or MRI measures of disease progression, suggests that there is a loss of
      distributed activation in more disabled patients. This may inform future
      treatment strategies.

PMID- 16619124
TI  - Upside down reversal of vision due to an isolated acute cerebellar ischemic
      infarction.

PMID- 16619125
TI  - Saccade initiation in ocular motor apraxia.

PMID- 16619126
TI  - Swallowing in degenerative ataxias.

PMID- 16619127
TI  - Persistent multifocal myoclonus following Russian spring summer encephalitis.

PMID- 16619128
TI  - Syringomyelia extending to the corona radiata.

PMID- 16619129
TI  - Acute toxic polyradiculopathy after exorbitant intracarotid substance abuse.

PMID- 16619131
TI  - Effects of freezing and cryopreservation on the mechanical properties of
      arteries.
AB  - Cryoplasty, a freezing therapy, is being used for the treatment of restenosis in
      peripheral arteries. In addition, cryo-preserved arteries are increasingly used
      in vascular grafts. While studies are being performed to establish the efficacy
      of such treatments, very little is known about the postcryosurgical or postcryo
      preservation changes in mechanical properties of the arteries. Few studies have
      examined the effect of freezing in the absence of cryoprotective agents (CPAs),
      and the several studies done in the presence of CPAs have given mixed results. To
      examine this issue further, we froze pig femoral arteries in a controlled rate
      freezer, using an aluminum probe, both in the presence at (-80 degrees C to 1
      degrees C/min) and absence (at -20 degrees C for 2 or 5 mins) of CPA and Fetal
      bovine serum (FBS). Following freezing, artery samples were subjected to uniaxial
      tensile testing. The weights of the tissue were measured before and after
      freezing. Our results suggest that freezing does have an effect on stress-strain
      properties, particularly in the low stress region corresponding to physiological
      conditions. The mechanisms of this change in mechanical properties may include
      the loss of smooth muscle cell viability, damage to extra cellular matrix (ECM),
      bulk redistribution of water, or changes in alignment caused by ice crystal
      growth. In the case of samples frozen in the absence of CPA or FBS, the results
      indicated a drastic reduction in weight of the tissue suggesting the importance
      of bulk water redistribution as one underlying mechanism. To further examine
      potential mechanisms, we subjected cryopreserved vessels to the same uniaxial
      tests. The extent of changes in mechanical properties and bulk water
      redistribution was greatly attenuated; reinforcing that water movement might play
      a role in the changes observed with freezing.

PMID- 16619130
TI  - Lactate production upon short-term non-ischemic forearm exercise in mitochondrial
      disorders and other myopathies.
AB  - BACKGROUND: The nonischemic forearm exercise test (NIFET) has been shown to be as
      effective as the classic ischemic forearm exercise test (IFET) in the diagnosis
      of patients with McArdle disease. Recently, the lactate increase normalized to
      the mechanical energy production in NIFET was suggested to have a intermediate
      sensitivity and satisfactory specifity for the screening of mitochondrial
      disorders. METHODS: NIFET at 80% maximal contraction force (MCF) was performed in
      normal controls (n = 41), patients with mitochondrial disorders (n = 15) and
      other myopathies (diseased controls, n = 20). 26 healthy volunteers also
      underwent IFET at 80% MCF. The ratio of lactate increase and workload was defined
      as specific lactate production (mmol x s/N x l). RESULTS: In normal controls
      there was no significant different lactate increase during NIFET and IFET. The
      workload performed showed only a weak significant positive correlation with the
      lactate increase in the NIFET in normal controls (r(2) = 0.20) but not in IFET
      and NIFET with patients. A moderate negative correlation of specific lactate
      production and the absolute workload was found in all groups and in both
      protocols (r(2) = 0.22-0.34). The specific lactate production was highest in
      patients with other myopathies, intermediate in patients with mitochondrial
      disorders and lowest in normal controls. NIFET showed a sensitivity of only 20 %
      and a specifity of 95% for normal controls, but only 75 % for diseased controls.
      CONCLUSION: The specific lactate production during NIFET is neither sufficiently
      specific nor sensitive for the diagnosis of mitochondrial disorders. Increased
      specific lactate production during rest-to-work transition period might be caused
      by increased acetyl group deficits.

PMID- 16619132
TI  - Spinal cord transcriptome analysis using suppression subtractive hybridization
      and mirror orientation selection.
AB  - Comparison of cDNA libraries derived from the spinal cord with those derived from
      the visual cortex by means of forward and reverse subtractive hybridization
      resulted in the cataloguing of 60 genes differentially expressed in the spinal
      cord. 1. The differentially expressed genes represent a mixture of novel and
      known sequences with known and unknown protein products. 2. The possibility that
      the subtraction process was simply overwhelmed by background sequences was
      significantly reduced by several observations including comparisons between
      suppression subtractive hybridization (SSH) and mirror orientation selection
      (MOS). 3. Nearly half of all genes up-regulated in the spinal cord are of myelin
      origin. 4. Twenty-five percent of all up-regulated clones in the spinal cord
      versus the visual cortex are for proteolipid protein. 5. Ten percent of all up
      regulated clones in spinal cord versus visual cortex are for ferretin heavy
      chain, which is known to be produced in oligodendroglial cells in the CNS. 6. Two
      of the up-regulated sequences, proteolipid protein and N-myc down-regulated gene
      4, are identified with genes known to directly affect neuron survival. 7. Two of
      the up-regulated genes, ferritin and transferrin, are indirectly associated with
      apoptosis through their ability to sequester iron and reduce free radical
      formation.

PMID- 16619133
TI  - Alpha-tocopherol and ascorbic acid administration prevents the impairment of
      brain energy metabolism of hyperargininemic rats.
AB  - 1. We have previously demonstrated that arginine administration induces oxidative
      stress and compromises energy metabolism in rat hippocampus. In the present study
      we initially investigated the influence of pretreatment with alpha-tocopherol and
      ascorbic acid on the effects produced by arginine on hippocampus energy
      metabolism. We also tested the effect of acute administration of arginine on
      various parameters of energy metabolism, namely glucose uptake, lactate release
      and on the activities of succinate dehydrogenase, complex II and cytochrome c
      oxidase in rat cerebellum, as well as the influence of pretreatment with alpha
      tocopherol and ascorbic acid on the effects elicited by arginine on this
      structure. 2. Sixty-day-old female Wistar rats were treated with a single i.p.
      injection of saline (control) or arginine (0.8 g/kg) and were killed 1 h later.
      In another set of experiments, the animals were pretreated for 1 week with daily
      i.p. administration of saline (control) or alpha-tocopherol (40 mg/kg) and
      ascorbic acid (100 mg/kg). Twelve hours after the last injection of the
      antioxidants the rats received one i.p. injection of arginine (0.8 g/kg) or
      saline and were killed 1 h later. 3. Results showed that arginine administration
      significantly increased lactate release and diminished glucose uptake and the
      activities of succinate dehydrogenase and complex II in rat cerebellum. In
      contrast, complex IV (cytochrome c oxidase) activity was not changed by this
      amino acid. Furthermore, pretreatment with alpha-tocopherol and ascorbic acid
      prevented the impairment of energy metabolism caused by hyperargininemia in
      cerebellum and hippocampus of rats.

PMID- 16619134
TI  - Effects of genetic and procedural variation on measurement of alcohol sensitivity
      in mouse inbred strains.
AB  - Mice from eight inbred strains were studied for their acute sensitivity to
      ethanol as indexed by the degree of hypothermia (HT), indexed as the reduction
      from pre-injection baseline of their body temperature. Two weeks later, mice were
      tested for their loss of righting reflex (LRR) after a higher dose of ethanol.
      The LRR was tested using the "classical" method of watching for recovery in
      animals placed on their backs in a V-shaped trough and recording duration of LRR.
      In a separate test, naive animals of the same strains were tested for HT
      repeatedly to assess the development of rapid (RTOL) and chronic tolerance
      (CTOL). We have recently developed a new method for testing LRR that leads to a
      substantial increase in the sensitivity of the test. Strains also have been found
      to differ in the new LRR test, as well as in the development of acute functional
      tolerance (AFT) to this response. In addition, our laboratory has periodically
      published strain difference data on the older versions of the HT and LRR
      responses. The earlier tests used some of the exact substrains tested currently,
      while for some strains, different substrains (usually, Nih versus Jax) were
      tested. We examined correlations of strain means to see whether patterns of
      strain differences were stable across time and across different test variants
      assessing the same behavioral construct. HT strain sensitivity scores were
      generally highly correlated across a 10-23 years period and test variants. The
      CTOL to HT was well-correlated across studies, and was also genetically similar
      to RTOL. The AFT, however, was related to neither RTOL nor CTOL, although this
      may be because different phenotypic end points were compared. The LRR data, which
      included a variant of the classical test, were not as stable. Measures of LRR
      onset were reasonably well correlated, as were those taken at recovery (e.g.,
      duration). However, the two types of measures of LRR sensitivity to ethanol
      appear to be tapping traits that differ genetically. Also, the pattern of genetic
      correlation between HT and LRR initially reported in 1983 was not seen in current
      and contemporaneous studies. In certain instances, substrain seems to matter
      little, while in others, substrains differed a great deal. These data are
      generally encouraging about the stability of genetic differences.

PMID- 16619135
TI  - Genetic and environmental vulnerabilities underlying adolescent substance use and
      problem use: general or specific?
AB  - Are genetic and environmental risks for adolescent substance use specific to
      individual substances or general across substance classes? We examined this
      question in 645 monozygotic twin pairs, 702 dizygotic twin pairs, 429 biological
      sibling pairs, and 96 adoptive (biologically unrelated) sibling pairs ascertained
      from community-based samples, and ranging in age from 12 to 18 years. Substance
      use patterns and symptoms were assessed using structured psychiatric interviews.
      Biometrical model fitting was carried out using age- and sex-specific thresholds
      for (a) repeated use and (b) problem use, defined as one or more DSM-IV symptoms
      of abuse or dependence. We hypothesized that problem use would be more heritable
      than use in adolescence, and that both genetic and environmental risks underlying
      tobacco, alcohol, and marijuana use and problem use would be significantly
      correlated. Results of univariate analyses suggested significant heritable
      factors for use and problem use for all substances with the exception of alcohol
      use. Shared environmental factors were important in all cases and special twin
      environmental factors were significant for tobacco use, tobacco problem use, and
      alcohol use. Multivariate analyses yielded significant genetic correlations
      between each of the substances (for both levels studied), and significant shared
      environmental correlations among use variables only. Our results suggest that
      tobacco, alcohol, and marijuana problem use are mediated by common genetic
      influences, but shared environmental influences may be more substance-specific
      for problem use.

PMID- 16619136
TI  - Non-DNA-binding antibodies in patients with lupus nephritis could recognize
      membrane proteins of glomerular mesangial cells.
AB  - Lupus nephritis (LN) is a prototypic autoimmune disease, however, the precise
      immuno-pathogenesis of LN remains to be elucidated. In our previous studies,
      autoantibodies against mesangial cells had been identified in sera from patients
      with lupus nephritis and could bind the membrane proteins of human mesangial
      cells (HMC) directly through antigen-antibody interaction without DNA bridge. The
      current study is to investigate whether the autoantibodies were associated with
      anti-DNA antibodies and their target antigens distribution in different cell
      types. Sera from nine patients with renal biopsy proven lupus nephritis with
      positive anti-dsDNA antibodies and four healthy subjects were collected. IgG was
      isolated by Protein G affinity chromatography and then non-DNA-binding IgG
      fractions were obtained after deletion of anti-DNA antibodies using a DNA
      cellulose affinity column. Membrane proteins, obtained from HMC, human umbilical
      vein endothelial cells (HUVEC), peripheral mononuclear cells by sonication and
      sequential centrifugation, were solubilized and applied in Western-blot analysis
      to characterize the target antigens. In results, the non-DNA-binding IgG
      fractions from sera of patients with lupus nephritis could blot the protein(s) of
      HMC membrane at 74, 63, and 42 kD. However, only a similar 74-kD protein could be
      blotted on membrane of HUVEC, and the target antigens on membranes of mononuclear
      cells were heterogeneous. In conclusion, our preliminary study had demonstrated
      that non-DNA binding autoantibodies against mesangial cells could be found in
      sera from patients with lupus nephritis. Although the target antigens might not
      be cell specific, the roles of these autoantibodies in the pathogenesis of lupus
      nephritis need further investigation.

PMID- 16619137
TI  - Social class, race, and ethnicity: career interventions for women domestic
      violence survivors.
AB  - This story describes a community intervention study conducted with women domestic
      violence survivors and a research dilemma related to the complex
      interrelationships between women's social class, race and ethnicity, and career
      development needs and experiences. The author presents diversity and research
      dilemmas related to facilitating women's critical consciousness of power dynamics
      at work in their lives. The influence of community context, career intervention
      curricula, and research team members' values on research decisions are described.
      This story highlights the importance of researchers examining their values and
      how those values impact the communities that they serve.

PMID- 16619138
TI  - A bilingual "neighborhood club": intervening with children exposed to urban
      violence.
AB  - Mental health practitioners have offered relatively little in response to the
      pervasive community violence faced by many children living in impoverished
      neighborhoods. The "neighborhood club" is a school-based, short-term, support
      group designed to assist children with the psychological impact of exposure to
      community violence. Ten "neighborhood clubs" were conducted in two public
      elementary schools in Detroit, Michigan. This paper reviews the implementation of
      a bilingual "neighborhood club," undertaken to better serve the Spanish-speaking
      Latino students in a school community. We discuss many of the rewards and
      challenges of conducting a bilingual, multicultural support group for children
      and conclude that a bilingual support group provides all children with a model
      that validates ethnic and cultural diversity while also building empathic bonds
      based on mutually-reinforcing, common experiences.

PMID- 16619139
TI  - On the edge of diversity: bringing African Americans and Latinos together in a
      neighborhood group.
AB  - This article describes challenges we encountered when organizing a group of
      African Americans and Latinos in a community where ethnic tensions had been
      normative. We relate how the first author, a Caucasian with a university
      affiliation, entered this diverse community and employed ethnographic methods in
      an attempt to understand it. The ethnography provides a context for the principal
      challenge we encountered: ensuring that the group had ethnic balance. Focusing on
      the group's first meeting, we describe the uncertainty of whether our work would
      be helpful or harmful to the community. We conclude with reflections on the gaps
      between science and practice in diverse communities; the utility and limits of
      ethnography; the multiple ecological levels of influence on the community;
      dilemmas around a White male taking proactive stances while trying to empower a
      group consisting mostly of women of color; and the influence of values we brought
      to the community.

PMID- 16619140
TI  - Gender role orientation and anxiety symptoms among African american adolescents.
AB  - The present study evaluated gender role theory as an explanation for the observed
      gender differences in anxiety symptoms among adolescents. Specifically, the
      relation between gender, gender role orientation (i.e., masculinity and
      femininity), self-esteem, and anxiety symptoms was examined in a community sample
      of 114 African Americans aged 14 to 19 (mean age 15.77; 57 girls). Results
      revealed that masculinity was negatively associated with anxiety symptoms whereas
      femininity was positively associated with anxiety symptoms. Gender role
      orientation accounted for unique variance in anxiety scores above biological
      gender and self-esteem, and self-esteem moderated the relation between femininity
      (but not masculinity) and overall anxiety symptoms. Consistent with research on
      children and Caucasians, findings supported gender role theory as a partial
      explanation for the observed gender disparity in anxiety symptoms among African
      American adolescents.

PMID- 16619141
TI  - Predictors of attributional style change in children.
AB  - A number of studies have supported the hypothesis that negative attributional
      styles may confer vulnerability to the development of depression. The goal of
      this study was to explore factors that may contribute to the development of
      negative attributional styles in children. As hypothesized, elevated levels of
      depressive symptoms and hopelessness at the initial assessment predicted negative
      changes in children's attributional styles over the 6-month follow-up period. In
      addition, elevated levels of verbal victimization occurring between the 2
      assessments, as well as that occurring in the 6 months preceding the initial
      assessment, prospectively predicted negative changes in children's attributional
      styles over the follow-up. Further, initial depressive symptoms and verbal
      victimization during the follow-up continued to significantly predict
      attributional style change even when the overlap among the predictors was
      statistically controlled. Contrary to the hypotheses, however, neither parent
      reported levels of overall negative life events nor parents' attributions for
      their children's events predicted changes in children's attributional styles.

PMID- 16619143
TI  - Apparent resolution of type 2 diabetes mellitus after initiation of potent
      antiretroviral therapy in a man from Africa with HIV infection.
AB  - We describe a 52-year-old African man with human immunodeficiency virus infection
      and type 2 diabetes mellitus whose diabetes resolved as viral replication was
      suppressed with protease inhibitor-based antiretroviral therapy. This case
      suggests that human immunodeficiency virus infection itself can precipitate overt
      diabetes mellitus.

PMID- 16619144
TI  - Association between rmpA and magA genes and clinical syndromes caused by
      Klebsiella pneumoniae in Taiwan.
AB  - BACKGROUND: The association of the magA gene with the hypermucoviscosity
      phenotype relevant to the pathogenesis of Klebsiella pneumoniae liver abscess has
      been reported in Taiwan. Similarly, the rmpA gene, known as a positive regulator
      of extracapsular polysaccharide synthesis that confers a mucoid phenotype, may be
      another candidate gene causing hypermucoviscosity. However, the association of
      rmpA with K. pneumoniae clinical syndromes is unreported. We aimed to investigate
      the clinical correlation between rmpA and primary Klebsiella abscess, focusing on
      sites other than the liver. METHODS: From July 2003 through December 2004, a
      total of 151 K. pneumoniae isolates recovered from 151 patients with bacteremia
      were collected from 2 large medical centers in southern Taiwan. Clinical data
      were collected from medical records. The genes rmpA and magA were amplified by
      polymerase chain reaction using specific primers. RESULTS: The prevalences of
      hypermucoviscosity, rmpA, and magA were 38%, 48%, and 17%, respectively. As
      determined by statistical multivariate analysis, strains carrying rmpA were
      significantly associated with the hypermucoviscosity phenotype, and there was a
      significant correlation with purulent tissue infections, such as liver abscess
      and lung, neck, psoas muscle, or other focal abscess. CONCLUSION: Our data
      support a statistical correlation between the rmpA gene and virulence in terms of
      abscess formation for these hypermucoviscous K. pneumoniae strains.
      Hypermucoviscosity associated with rmpA, together with a thorough physical
      examination, may be helpful as a guide to carry out appropriate diagnostic tests
      on patients with an initially unknown source of K. pneumoniae bacteremia,
      particularly when looking for the occurrence of an underlying abscess.

PMID- 16619145
TI  - Hypermucoviscosity: an extremely sticky phenotype of Klebsiella pneumoniae
      associated with emerging destructive tissue abscess syndrome.

PMID- 16619146
TI  - High diversity of group A streptococcal emm types among healthy schoolchildren in
      Ethiopia.
AB  - BACKGROUND: Although the prevalence of rheumatic heart disease in Ethiopia is one
      of the highest in the world, the epidemiology of group A streptococci (GAS) in
      this country is little known. GAS typing is a hallmark of both the epidemiology
      and understanding of diseases caused by these organisms. We have therefore
      conducted this study to investigate the emm (M-protein gene) type distribution of
      GAS carriers among Ethiopian schoolchildren. METHODS: In the present study, we
      performed emm typing of 82 GAS isolates collected from the throats of healthy
      schoolchildren (6-14 years of age) residing in 3 different urban sites in
      Ethiopia: Addis Ababa, Gondar, and Dire Dawa. RESULTS: We report high diversity
      of GAS isolates recovered from healthy schoolchildren. Eighty-two isolates
      represented 43 different sequence types. Thirteen newly described subtypes were
      detected in this study. Of the emm types prevalent in the study communities, 46%
      were not included in the 26-valent GAS vaccine. CONCLUSIONS: The high diversity
      of emm types encountered within 3 months of collection suggest that production of
      a vaccine candidate based on the M-protein amino termini appears to be
      impractical for this population. We suggest that investigations of other vaccine
      candidates, including the C5a peptidase, GAS carbohydrate, and fibronectin
      binding proteins, as well as conserved M-protein region vaccines, should be
      intensified to address the needs of this population.

PMID- 16619147
TI  - Low-level fluoroquinolone resistance among Campylobacter jejuni isolates in
      Australia.
AB  - BACKGROUND: Ciprofloxacin-resistant Campylobacter jejuni isolates obtained from
      infected patients in Australia have not been detected in studies of isolates from
      specific geographic areas. The Australian government has prohibited the use of
      fluoroquinolone in food-producing animals. To assess the impact of this policy,
      we have examined the antimicrobial susceptibility of isolates from 5 Australian
      states. METHODS: We conducted a period-prevalence survey of the susceptibility of
      C. jejuni isolates to 10 antimicrobial agents. C. jejuni isolates obtained from
      585 patients from 5 Australian states (Queensland, South Australia, Tasmania,
      Victoria, and Western Australia) were identified by means of notifiable disease
      databases and were systematically selected from September 2001 to August 2002.
      RESULTS: Among locally acquired infections, only 2% of isolates (range, 0%-8% in
      different states) were resistant to ciprofloxacin. The locally acquired isolates
      also exhibited resistance to sulfisoxazole (55%), ampicillin (46%), roxithromycin
      (38%), tetracycline (7%), nalidixic acid (6%), chloramphenicol (3%), erythromycin
      (3%), gentamicin (2%), and kanamycin (0.2%). Treatment with antimicrobial agents
      in the 4 weeks before onset was not associated with ciprofloxacin resistance.
      CONCLUSIONS: The very low level of ciprofloxacin resistance in C. jejuni isolates
      likely reflects the success of Australia's policy of restricting use of
      fluoroquinolones in food-producing animals.

PMID- 16619148
TI  - Molecular epidemiology of pleural and other extrapulmonary tuberculosis: a
      Maryland state review.
AB  - BACKGROUND: Limited information exists about the current epidemiological
      characteristics of extrapulmonary tuberculosis. However, pleural tuberculosis is
      usually considered to be a manifestation of primary tuberculosis. Our objective
      was to use molecular epidemiological techniques to describe the occurrence of
      pleural and other extrapulmonary tuberculosis in Maryland, a state with moderate
      tuberculosis incidence. METHODS: We surveyed tuberculosis cases reported with a
      single site of disease in Maryland from 1996 through 2001. Genotyping of
      Mycobacterium tuberculosis isolates was performed with an IS6110-based
      restriction fragment-length polymorphism analysis. DNA clustering of strains with
      >5 IS6110 bands, with supporting epidemiologic information on patients, served as
      a proxy for recent transmission. RESULTS: A total of 1811 patients with
      tuberculosis were reported (incidence, 5.9 cases per 100,000 population). Of 1411
      patients (77.9%) with cultures positive for M. tuberculosis, 1246 (88.3%) had a
      single site of disease, with 934 (75.0%) of these isolates having >5 IS6110
      bands. Of the 934 patients included in the analyses, 729 (78.0%) had pulmonary
      tuberculosis, and 205 (22.0%) had extrapulmonary tuberculosis; of the latter
      group, 46 patients had pleural disease, and 159 patients had nonrespiratory
      disease. In multivariate analyses, patients with pleural tuberculosis were not
      significantly associated with clustered strains, compared with patients with
      nonrespiratory or pulmonary tuberculosis disease. Having a DNA-clustered strain
      was negatively associated with nonrespiratory tuberculosis, compared with
      pulmonary disease (adjusted odds ratio, 0.48; P = .003). CONCLUSIONS:
      Nonrespiratory extrapulmonary tuberculosis is less likely than pulmonary
      tuberculosis to be a result of recent infection. Pleural tuberculosis is not an
      appropriate indicator for recent transmission among our population.

PMID- 16619149
TI  - Outcome of treatment for congenital toxoplasmosis, 1981-2004: the National
      Collaborative Chicago-Based, Congenital Toxoplasmosis Study.
AB  - BACKGROUND: Without treatment, congenital toxoplasmosis has recurrent,
      recrudescent, adverse outcomes. Long-term follow-up of infants with congenital
      toxoplasmosis treated throughout their first year of life with pyrimethamine and
      sulfadiazine has not been reported. METHODS: Between 1981 and 2004, one hundred
      twenty infants (current mean age +/- standard deviation, 10.5 +/- 4.8 years) with
      congenital toxoplasmosis were treated with 1 of 2 doses of pyrimethamine plus
      sulfadiazine; therapy was initiated shortly after birth and continued for 12
      months. Children who received treatment were evaluated at birth and at
      predetermined intervals; the focus of the evaluations was on prespecified end
      points: motor abnormalities, cognitive outcome, vision impairment, formation of
      new eye lesions, and hearing loss. RESULTS: Treatment of infants without
      substantial neurologic disease at birth with pyrimethamine and sulfadiazine for 1
      year resulted in normal cognitive, neurologic, and auditory outcomes for all
      patients. Treatment of infants who had moderate or severe neurologic disease (as
      defined in this article in the Treatments subsection of Methods) at birth
      resulted in normal neurologic and/or cognitive outcomes for >72% of the patients,
      and none had sensorineural hearing loss. Ninety-one percent of children without
      substantial neurologic disease and 64% of those with moderate or severe
      neurologic disease at birth did not develop new eye lesions. Almost all of these
      outcomes are markedly better than outcomes reported for children who were
      untreated or treated for 1 month in earlier decades (P<.01 to P<.001). Sex and
      severity of disease were comparable in our 2 treatment groups, and no significant
      differences in efficacy or toxicity were noted between the 2 treatment groups (P
      > .05). CONCLUSIONS: Although not all children did well with treatment, the
      favorable outcomes we noted indicate the importance of diagnosis and treatment of
      infants with congenital toxoplasmosis.

PMID- 16619150
TI  - Time to screen for congenital toxoplasmosis?

PMID- 16619151
TI  - Posaconazole as salvage treatment for invasive fusariosis in patients with
      underlying hematologic malignancy and other conditions.
AB  - BACKGROUND: Conventional amphotericin B-based antifungal therapy for invasive
      fusariosis in patients with a hematologic malignancy results in a > or = 70%
      failure rate. Posaconazole is a broad-spectrum antifungal agent with in vitro and
      in vivo activity against Fusarium species. METHODS: In this retrospective
      analysis of patients from 3 open-label clinical trials, we evaluated posaconazole
      for the treatment of invasive fusariosis. Twenty-one patients with proven or
      probable invasive fusariosis who had disease refractory to or who were intolerant
      of standard antifungal therapy received oral posaconazole suspension (800 mg per
      day in divided doses) as salvage therapy. RESULTS: Successful outcome occurred in
      10 (48%) of all 21 patients. Among patients with leukemia who received
      posaconazole therapy for >3 days, the overall success rate was 50%; for patients
      who recovered from myelosuppression, the success rate was 67%, compared with 20%
      for those with persistent neutropenia. CONCLUSION: These results suggest that
      posaconazole is useful for the treatment of invasive fusariosis.

PMID- 16619152
TI  - A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone
      versus in combination with an antibody-based inhibitor of heat shock protein 90
      in patients with invasive candidiasis.
AB  - BACKGROUND: Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody
      against heat shock protein 90 that, in laboratory studies, was revealed to have
      synergy with amphotericin B against a broad spectrum of Candida species. METHODS:
      A double-blind, randomized study was conducted to determine whether lipid
      associated amphotericin B plus Mycograb was superior to amphotericin B plus
      placebo in patients with culture-confirmed invasive candidiasis. Patients
      received a lipid-associated formulation of amphotericin B plus a 5-day course of
      Mycograb or placebo, having been stratified on the basis of Candida species
      (Candida albicans vs. non-albicans species of Candida). Inclusion criteria
      included clinical evidence of active infection at trial entry plus growth of
      Candida species on culture of a specimen from a clinically significant site
      within 3 days after initiation of study treatment. The primary efficacy variable
      was overall response to treatment (clinical and mycological resolution) by day
      10. RESULTS: Of the 139 patients enrolled from Europe and the United States, 117
      were included in the modified intention-to-treat population. A complete overall
      response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B
      group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy
      group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79; P<.001).
      The following efficacy criteria were also met: clinical response (52% vs. 86%;
      OR, 5.4; 95% CI, 2.21-13.39; P<.001), mycological response (54% vs. 89%; OR, 7.1;
      95% CI, 2.64-18.94; P<.001), Candida-attributable mortality (18% vs. 4%; OR, 0.2;
      95% CI, 0.04-0.80; P = .025), and rate of culture-confirmed clearance of the
      infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well
      tolerated. CONCLUSIONS: Mycograb plus lipid-associated amphotericin B produced
      significant clinical and culture-confirmed improvement in outcome for patients
      with invasive candidiasis.

PMID- 16619153
TI  - The third age of antimicrobial therapy.

PMID- 16619154
TI  - Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis.
AB  - BACKGROUND: A double-sandwich enzyme-linked immunosorbent galactomannan assay has
      been approved for surveillance for invasive aspergillosis in immunocompromised
      patients. We undertook a meta-analysis to assess the accuracy of a galactomannan
      assay for diagnosing invasive aspergillosis. METHODS: Studies of the
      galactomannan assay that used the European Organization for Research and
      Treatment of Cancer or similar criteria as a reference standard and provided data
      to calculate sensitivity and specificity were included. Pooled sensitivity and
      specificity and summary measures of accuracy, Q* (the upper left-most point on
      the summary receiver-operating characteristic curve), mean D (a log odds ratio),
      and Youden index were calculated. Subgroup analyses were performed to explore
      heterogeneity. RESULTS: Twenty-seven studies from 1966 to 28 February 2005 were
      included. Overall, the galactomannan assay had a sensitivity of 0.71 (95%
      confidence interval [CI], 0.68-0.74) and specificity of 0.89 (95% CI, 0.88-0.90)
      for proven cases of invasive aspergillosis. The Youden index, mean D, and Q* were
      0.54 (95% CI, 0.41-0.65), 2.74 (95% CI, 21.12-3.36), and 0.80 (95% CI, 0.74
      0.86), respectively, indicating moderate accuracy. Subgroup analyses showed that
      the performance of the test differed by patient population and type of reference
      standard used. Significant heterogeneity was present. CONCLUSIONS: The
      galactomannan assay has moderate accuracy for diagnosis of invasive aspergillosis
      in immunocompromised patients. The test is more useful in patients who have
      hematological malignancy or who have undergone hematopoietic cell transplantation
      than in solid-organ transplant recipients. Further studies with attention to the
      impact of antifungal therapy, rigorous assessment of false-positive test results,
      and assessment of the utility of the test under nonsurveillance conditions are
      needed.

PMID- 16619155
TI  - Galactomannan and the diagnosis of invasive aspergillosis.

PMID- 16619156
TI  - Detection and discrimination of herpes simplex viruses, Haemophilus ducreyi,
      Treponema pallidum, and Calymmatobacterium (Klebsiella) granulomatis from genital
      ulcers.
AB  - BACKGROUND: Genital ulcer disease (GUD) is commonly caused by pathogens for which
      suitable therapies exist, but clinical and laboratory diagnoses may be
      problematic. This collaborative project was undertaken to address the need for a
      rapid, economical, and sensitive approach to the detection and diagnosis of GUD
      using noninvasive techniques to sample genital ulcers. METHODS: The genital ulcer
      disease multiplex polymerase chain reaction (GUMP) was developed as an inhouse
      nucleic acid amplification technique targeting serious causes of GUD, namely,
      herpes simplex viruses (HSVs), H. ducreyi, Treponema pallidum, and Klebsiella
      species. In addition, the GUMP assay included an endogenous internal control.
      Amplification products from GUMP were detected by enzyme linked amplicon
      hybridization assay (ELAHA). RESULTS: GUMP-ELAHA was sensitive and specific in
      detecting a target microbe in 34.3% of specimens, including 1 detection of HSV-1,
      three detections of HSV-2, and 18 detections of T. pallidum. No H. ducreyi has
      been detected in Australia since 1998, and none was detected here. No
      Calymmatobacterium (Klebsiella) granulomatis was detected in the study, but there
      were 3 detections during ongoing diagnostic use of GUMP-ELAHA in 2004 and 2005.
      The presence of C. granulomatis was confirmed by restriction enzyme digestion and
      nucleotide sequencing of the 16S rRNA gene for phylogenetic analysis.
      CONCLUSIONS: GUMP-ELAHA permitted comprehensive detection of common and rare
      causes of GUD and incorporated noninvasive sampling techniques. Data obtained by
      using GUMP-ELAHA will aid specific treatment of GUD and better define the
      prevalence of each microbe among at-risk populations with a view to the
      eradication of chancroid and donovanosis in Australia.

PMID- 16619157
TI  - Pertussis serostatus among neonates born to Hispanic women.
AB  - The reasons for the higher pertussis incidence among Hispanic infants, compared
      with among infants of other ethnicities, are unknown. The geometric mean
      concentration of pertussis toxin-specific immunoglobulin G in serum samples from
      220 Hispanic neonates was 8.45 EU/mL, as determined by enzyme-linked
      immunosorbent assay, and it was significantly lower if mothers were adolescents
      (4.63 EU/mL; P < or =.001). A lack of maternal immunity is one explanation for
      pertussis susceptibility in very young Hispanic infants.

PMID- 16619158
TI  - The poor prognosis of central nervous system cryptococcosis among
      nonimmunosuppressed patients: a call for better disease recognition and
      evaluation of adjuncts to antifungal therapy.
AB  - We describe 9 nonimmunosuppressed patients with central nervous system
      cryptococcosis. Morbidity and mortality were high, especially among patients with
      cerebral infarcts. This was attributed to delayed diagnosis and apparent sequelae
      of overwhelming host immune responses. We present clues suggesting the diagnosis.
      Increased recognition and timely diagnosis of this condition may improve
      outcomes.

PMID- 16619159
TI  - HIV infection and dementia in older adults.
AB  - Human immunodeficiency virus (HIV) infection in older patients is becoming
      increasingly common as seropositive individuals live longer because of long-term
      antiretroviral treatment. Simultaneously, the development and expression of
      dementia among HIV-infected patients is evolving in the era of highly active
      antiretroviral therapy (HAART) and immune reconstitution. How long-term HAART
      interacts with chronic HIV infection and advanced age with regard to cognition is
      not fully understood. This article provides an overview of HIV cognitive
      impairment as it relates to aging and presents some emerging issues in the field.
      Particular emphasis is placed on describing the changing landscape of HIV-related
      cognitive impairment and discussing possible concerns regarding the long-term
      effects of antiretroviral treatment. A brief discussion of potential adjunctive
      therapies to reduce cognitive symptoms associated with HIV infection in older
      individuals is provided.

PMID- 16619160
TI  - Common ground for the control of multidrug-resistant Salmonella in ground beef.
AB  - A strategy to combat multidrug-resistant (MDR) Salmonella in ground beef is
      urgently needed. A national multi-disciplinary meeting reviewed the epidemiology
      of MDR Salmonella infection and contamination in humans, animals, and retail
      meat. In spite of a recent overall decrease in human MDR Salmonella isolates,
      certain types, such as Salmonella enterica serotype Newport multidrug-resistant
      AmpC strain and Salmonella enterica serotype Typhimurium definitive type (DT)
      104, have persisted, and several recent large outbreaks of human infection have
      occurred. Key agencies that contribute to a safe ground beef supply were
      represented at the meeting and contributed to the discussion of possible control
      strategies from the farm to the table. Several of the control strategies
      suggested are unpopular to some, including restricting the use of antimicrobial
      agents in food animals, designation of multidrug-resistant Salmonella as an
      adulterant in ground beef, and improving the mechanisms for product trace-back
      investigations. Nevertheless, enhanced farm-based animal infection control,
      judicious veterinary and human antibiotic use, regulatory controls, and consumer
      practices will lead to important industry, veterinary, and public health
      outcomes.

PMID- 16619161
TI  - Club drugs and HIV infection: a review.
AB  - Club drug use is common among populations with human immunodeficiency virus (HIV)
      and populations at high risk for HIV infection. Club drugs have a myriad of acute
      and chronic medical consequences. Club drug-related visits to the emergency
      department and admissions for treatment of substance use have increased
      dramatically over the past 15 years. Most epidemiological data support the role
      of club drugs in increasing sexual risk behavior, with some studies demonstrating
      an independent association between use of certain club drugs and HIV infection.
      The direct influence of club drugs on progression of HIV disease remains to be
      determined; however, club drugs may interact with certain retroviral medications
      and have been associated with decreased adherence to medication. Clinicians
      should ask all patients about patterns of club drug use, counsel patients about
      the risks associated with club drug use, and refer patients to appropriate
      behavioral treatment programs for substance use when clinically indicated.

PMID- 16619162
TI  - Comparison of a rule-based algorithm with a phenotype-based algorithm for the
      interpretation of HIV genotypes in guiding salvage regimens in HIV-infected
      patients by a randomized clinical trial: the mutations and salvage study.
AB  - BACKGROUND: There is still considerable uncertainty as to the best algorithm for
      interpreting human immunodeficiency virus (HIV) genotyping results. METHODS: A
      total of 318 subjects with HIV RNA levels of >1000 copies/mL were enrolled in 41
      centers throughout Italy from 2001 through 2003, stratified on the basis of their
      drug history, randomized (1:1) to 2 arms to have their treatments modified on the
      basis of the results of HIV genotyping (as interpreted by virtual phenotype
      analysis or with use of a rule-based interpretation system), and followed up for
      48 weeks. At least 1 nucleoside reverse-transcriptase inhibitor and 1 protease
      inhibitor had to be included in any new regimen; nonnucleoside reverse
      transcriptase inhibitor-naive patients were also prescribed a nonnucleoside
      reverse-transcriptase inhibitor. Only drugs licensed in Italy were allowed. The
      primary end point was a decrease in HIV RNA level to <400 copies/mL by week 12
      according to on-treatment analysis. RESULTS: The mean (+/- standard deviation)
      values at baseline were as follows: HIV RNA level, 4.1+/-0.74 log(10) copies/mL;
      CD4(+) T lymphocyte count, 410+/-262 cells/microL; reverse-transcriptase
      mutations, 4.8+/-2.9; and protease mutations, 2.8+/-2.5. There were 133 patients
      (41.8%) who were nonnucleoside reverse-transcriptase inhibitor naive and protease
      inhibitor experienced, 63 patients (19.8%) who were nonnucleoside reverse
      transcriptase inhibitor experienced and protease inhibitor naive, and 122
      patients (38.4%) who were 3-class experienced. A total of 192 patients completed
      12 weeks of the treatment regimen assigned at baseline; at 12 weeks, 66.3% of
      patients in the virtual phenotype arm and 71.3% of patients in the rule-based
      interpretation arm had HIV RNA levels of <400 copies/mL (P = .46). No
      statistically significant difference between arms was observed by intention-to
      treat analysis. CONCLUSION: Both the virtual phenotype and rule-based
      interpretation methods of HIV genotyping can guide the selection of effective
      antiretroviral drugs for a salvage regimen.

PMID- 16619163
TI  - Impact of hepatitis C virus coinfection on response to highly active
      antiretroviral therapy and outcome in HIV-infected individuals: a nationwide
      cohort study.
AB  - BACKGROUND: Coinfection with hepatitis C virus (HCV) in human immunodeficiency
      virus (HIV) type 1-infected patients may decrease the effectiveness of highly
      active antiretroviral therapy. We determined the impact of HCV infection on
      response to highly active antiretroviral therapy and outcome among Danish
      patients with HIV-1 infection. METHODS: This prospective cohort study included
      all adult Danish HIV-1-infected patients who started highly active antiretroviral
      therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV
      positive (positive HCV serological test and/or HCV PCR results [443 patients
      [16%]]), HCV negative (consistent negative HCV serological test results [2183
      patients [80%]]) and HCV-U (never tested for HCV [108 patients [4%]]). The study
      end points were viral load, CD4+ cell count, and mortality. RESULTS: Compared
      with the HCV-negative group, overall mortality was significantly higher in the
      HCV-positive group (mortality rate ratio, 2.4; 95% confidence interval [CI], 1.9
      3.0), as was liver disease-related mortality (mortality rate ratio, 16; 95% CI,
      7.2-33). Furthermore, patients in the HCV-positive group had a higher risk of
      dying with a prothrombin time <0.3, from acquired immunodeficiency syndrome
      related disease, and if they had a history of alcohol abuse. Although we observed
      no difference in viral load between the HCV-positive and HCV-negative groups, the
      HCV-positive group had a marginally lower absolute CD4+ cell count. CONCLUSIONS:
      HIV-HCV-coinfected patients are compromised in their response to highly active
      antiretroviral therapy. Overall mortality, as well as mortality from liver
      related and acquired immunodeficiency syndrome-related causes, is significantly
      increased in this patient group.

PMID- 16619164
TI  - HIV-associated renal diseases and highly active antiretroviral therapy-induced
      nephropathy.
AB  - Renal disease is becoming an increasingly prevalent entity in human
      immunodeficiency virus (HIV)-infected patients; it occurs in a variety of
      clinical settings and is associated with histopathological changes. HIV-related
      renal impairment can present as acute or chronic kidney disease; it can be caused
      directly or indirectly by HIV and/or by drug-related effects that are directly
      nephrotoxic or lead to changes in renal function by inducing metabolic
      vaculopathy and renal damage. Acute renal failure is frequently caused by the
      toxic effects of antiretroviral therapy or nephrotoxic antimicrobial substances
      used in the treatment of opportunistic infections. Chronic renal disease can be
      caused by multiple pathophysiological mechanisms, leading to HIV-associated
      nephropathy, a form of collapsing focal glomerulosclerosis, thrombotic
      microangiopathy, and various forms of immune complex glomerulonephritis. The
      increase in life expectancy and alteration of lipid metabolism due to receipt of
      highly active antiretroviral therapy are expected to result in an increased
      prevalence of diabetes and hypertension and, thus, to secondary diabetic and
      hypertensive renal damage. Antiretroviral agents, such as indinavir and
      tenofovir, have been associated with nephrotoxic drug effects that have been
      shown to be reversible in most cases. In this article, we review the current
      knowledge about acute and chronic HIV-associated renal disease, metabolic
      alterations and related nephropathies, and toxic drug effects of combination
      antiretroviral pharmacotherapy.

PMID- 16619165
TI  - Molecular epidemiology of tuberculosis.

PMID- 16619166
TI  - The diagnosis of latent tuberculosis in HIV-infected persons.

PMID- 16619168
TI  - Thrombocytopenia and anemia associated with linezolid in patients with kidney
      failure.

PMID- 16619170
TI  - Diagnostic insufficiency in Africa.

PMID- 16619171
TI  - The "Achilles heel" of global efforts to combat infectious diseases.

PMID- 16619172
TI  - Medical laboratory services in Africa deserve more.

PMID- 16619173
TI  - Methicillin-resistant Staphylococcus aureus bacteremia after isolation from
      urine.

PMID- 16619174
TI  - Clinical features of scrub typhus.

PMID- 16619175
TI  - Acute hearing loss and rickettsial diseases.

PMID- 16619176
TI  - Relationship of colonization with vancomycin-resistant enterococci and risk of
      systemic infection in patients with cancer.

PMID- 16619177
TI  - Preemptive antifungal therapy among neutropenic patients.

PMID- 16619179
TI  - What role for inactivated poliovirus vaccine in the eradication endgame?

PMID- 16619180
TI  - Analysis of reversions in the 5'-untranslated region of attenuated poliovirus
      after sequential administration of inactivated and oral poliovirus vaccines.
AB  - Replication of Sabin strains used in oral poliovirus vaccine (OPV) in the
      intestines of vaccine recipients leads to reversions that increase virus
      neurovirulence. Previously, a small study reported that prior immunization with
      inactivated poliovirus vaccine (IPV) resulted in faster accumulation of revertant
      virus, thus potentially increasing the risk of vaccine-associated paralytic
      poliomyelitis. We studied the impact that prior immunization with IPV and OPV has
      on shedding of revertant virus by healthy infants. By polymerase chain reaction
      (PCR), we amplified full-length poliovirus genomes directly from stool specimens
      from unimmunized infants and from infants previously immunized with IPV or OPV.
      The amplicons were used to quantify reversions in the 5'-untranslated region,
      using oligonucleotide microarray hybridization. Nearly all 140 samples that were
      PCR positive contained varying amounts of revertants of all 3 poliovirus
      serotypes. Polioviruses of Sabin types 2 and 3 reverted more easily than those of
      type 1. Prior vaccination with IPV did not increase the proportion of revertants
      after OPV administration.

PMID- 16619181
TI  - A phase 1 study of 4 live, recombinant human cytomegalovirus Towne/Toledo
      chimeric vaccines.
AB  - BACKGROUND: Human cytomegalovirus (HCMV) infection acquired in utero often
      results in severe consequences, including mental retardation and deafness.
      Although not evaluated for this indication, live attenuated HCMV vaccines based
      on the Towne strain are well-tolerated and have demonstrated moderate efficacy in
      other clinical settings. METHODS: To produce live HCMV vaccine candidates that
      retain the excellent safety profile of the Towne strain but are more immunogenic,
      the genomes of the Towne strain and the unattenuated HCMV Toledo strain were
      recombined to yield 4 independent chimeric vaccine candidates. These vaccine
      candidates were evaluated in 20 HCMV-seropositive persons, in a phase 1, double
      blinded, placebo-controlled trial. Participants received a single dose of vaccine
      or placebo, and the safety and tolerability of the vaccine candidates were
      evaluated. RESULTS: There was no difference in systemic symptoms between the
      vaccine and placebo recipients. As a group, vaccine recipients experienced more
      injection-site reactions than did placebo recipients; however, these were
      generally minor and short-lived. Vaccine virus could not be detected in blood,
      urine, or saliva samples obtained from any vaccine recipient. CONCLUSIONS: The
      Towne/Toledo chimeric vaccine candidates were well tolerated and did not cause
      systemic infection. Additional human trials are warranted to further evaluate the
      potential of these vaccine candidates as live virus vaccines.

PMID- 16619182
TI  - Nucleic acid testing for west nile virus RNA in plasma enhances rapid diagnosis
      of acute infection in symptomatic patients.
AB  - Although nucleic acid amplification testing (NAAT) for West Nile virus (WNV) is
      useful in screening blood donors, such methods have not been studied in
      symptomatic patients. For diagnosis of WNV infection, 1.0 mL of plasma was tested
      by NAAT, and WNV-specific immunoglobulin M was assayed. Of 276 WNV cases, 191
      were tested by both serology and NAAT. Of these, 86 (45.0%), 111 (58.1%), and 180
      (94.2%) were detected by NAAT, serology, and combined NAAT and serology,
      respectively. NAAT-based screening was most useful within 8 days of the onset of
      symptoms. Viremia is common in early symptomatic WNV infection, and NAAT enhances
      diagnostic yield.

PMID- 16619183
TI  - A novel ex vivo assay of interferon-based suppression, to predict the outcome of
      antiviral therapy for hepatitis C.
AB  - An ex vivo liver slice-culture method was used to develop a novel assay of
      pretherapy interferon-based suppression. To evaluate its clinical application, 45
      consecutive patients with chronic hepatitis C were included. They underwent the
      ex vivo antiviral assay, followed by a 24-week course of therapy with
      peginterferon and ribavirin. A stepwise logistic regression model was used to
      estimate the relationship between sustained virological response and the presence
      of various clinicopathological parameters. The results indicated that the
      presence of an interferon-based suppression effect in the ex vivo assay (odds
      ratio [OR], 12.454 [95% confidence interval {CI}, 1.115-139.090]; P=.0405),
      clinically diagnosed liver cirrhosis (OR, 0.081 [95% CI, 0.011-0.584]; P=.0126),
      and the portal-inflammation score (OR, 4.220 [95% CI, 1.264-14.085]; P=.0192)
      were independent determinants of sustained virological response. In conclusion,
      this new assay serves as an independent predictor of sustained virological
      response in interferon-based antiviral therapy.

PMID- 16619184
TI  - Association of transforming growth factor-beta 1 functional polymorphisms with
      natural clearance of hepatitis C virus.
AB  - Transforming growth factor (TGF)-beta 1 suppresses the proliferation and
      cytotoxicity of natural killer (NK) cells, which play critical roles in resolving
      hepatitis C virus (HCV) infection, especially during the acute phase. We examined
      230 anti-HCV antibody-positive subjects for HCV RNA and the -509T/C genotype in
      the TGF-beta 1 gene promoter. The -509CC genotype and the -509C allele were
      significantly associated with higher HCV clearance rates (P=.01) and with lower
      transcriptional activity. The genetic effect remained significant even after
      adjustment for a history of transfusion. Low TGF- beta 1 producers might have
      less suppression of NK cells and be more likely to resolve HCV infection.

PMID- 16619185
TI  - Resistance to antimony and treatment failure in human Leishmania (Viannia)
      infection.
AB  - BACKGROUND: Failure of antimonial therapy has been increasingly reported in
      anthroponotic visceral leishmaniasis and in cutaneous disease. The role of drug
      resistance in treatment failure has been difficult to ascertain because
      therapeutic response is multifactorial, and the efficacy of antimonial drugs
      depends on an effective immune response. In this study, we sought to determine
      whether standard treatment selects for resistant organisms and whether drug
      resistance contributes to treatment failure. METHODS: We evaluated the
      susceptibility to antimony of 19 strains isolated before treatment with meglumine
      antimoniate and 21 strains isolated at treatment failure from 20 patients. The
      50% effective dose (ED50) of antimony in the form of additive-free meglumine
      antimoniate was determined for intracellular amastigotes in human promonocytic U
      937 cells. RESULTS: Before treatment, 16% of strains (3/19) showed primary
      resistance (ED50 of >128 microg Sb/mL), whereas 84% (16/19) were susceptible
      (ED50 of <20 microg Sb/mL). However, 88% of susceptible strains (14/16) had ED90
      values of >128 microg Sb/mL. At treatment failure, 40% of strains (8/20) were
      resistant. Secondary resistance was documented in 4 patients. CONCLUSIONS:
      Primary and secondary resistance to antimony can contribute to treatment failure
      in American cutaneous leishmaniasis. Selection for resistance to antimony occurs
      during standard treatment with antimonial drugs, and primary resistance to
      antimony supports the plausibility of anthroponotic transmission.

PMID- 16619186
TI  - Suppression of prostaglandin E2 by malaria parasite products and antipyretics
      promotes overproduction of tumor necrosis factor-alpha: association with the
      pathogenesis of childhood malarial anemia.
AB  - Cytokines and effector molecules are important immunoregulatory molecules in
      human malaria. Tumor necrosis factor (TNF)-alpha limits malaria parasitemia but
      also promotes pathogenesis at high concentrations, whereas prostaglandin E2
      (PGE2) inhibits TNF-alpha production and is reduced in childhood malaria, at
      least in part, through suppression of cyclooxygenase (COX)-2 following the
      ingestion of Plasmodium falciparum hemozoin (pfHz; malarial pigment) by
      peripheral blood mononuclear cells (PBMCs). Although molecular interactions
      between TNF-alpha and PGE2 are largely unexplored in human malaria, results
      presented here show that pfHz-induced suppression of PBMC COX-2 gene products
      induces overproduction of TNF-alpha. Moreover, addition of exogenous PGE2 to pfHz
      treated PBMCs dose-dependently decreased TNF-alpha production, whereas
      experimental COX inhibitors and antipyretics used during human malaria generated
      increased TNF-alpha production. Healthy, malaria-exposed children had elevated
      levels of circulating bicyclo-PGE2/TNF-alpha, compared with children with
      malarial anemia (P<.01), with systemic bicyclo-PGE2 and TNF-alpha significantly
      associated with hemoglobin concentrations (r=0.745; P<.01). The results of the
      present study illustrate that pfHz-induced suppression of PGE2 promotes
      overproduction of TNF-alpha, which is associated with enhanced malarial anemia.

PMID- 16619187
TI  - BAT1, a putative anti-inflammatory gene, is associated with chronic Chagas
      cardiomyopathy.
AB  - BACKGROUND: It is not understood why only a subset of individuals infected with
      Trypanosoma cruzi develop chronic Chagas cardiomyopathy (CCC). Patients with CCC
      display high levels of circulating proinflammatory cytokines. Heart-infiltrating
      lymphocytes from patients with CCC also express proinflammatory cytokines (tumor
      necrosis factor- alpha and interferon- gamma ) that are detectable in biopsy
      samples and surgical heart-tissue samples. BAT1, a putative anti-inflammatory
      gene, presents functional polymorphisms in its promoter region that influence its
      transcriptional level. METHODS: We assessed, by polymerase chain reaction
      restriction fragment-length polymorphism analysis, BAT1 variants in the promoter
      region at positions -22C/G and -348C/T in 154 patients with CCC and in 76 T.
      cruzi-infected but asymptomatic (ASY) patients. RESULTS: Of the patients with
      CCC, 16% were homozygous for the -22C allele, compared with 4% of the ASY
      patients (P=.004; odds ratio [OR], 4.7 [95% confidence interval {CI}, 1.4-16]). A
      similar trend was observed for the -348C homozygotes (P=.01; OR, 1.9 [95% CI, 1.0
      3.5]). Susceptibility to CCC was conferred by the C variants at nt -22 (P=.003;
      OR, 1.8 [95% CI, 1.2-2.8]) and at nt -348 (P=.02; OR, 1.7 [95% CI, 1.0-2.8]).
      CONCLUSIONS: BAT1 variants previously associated with reduced expression of HLA-B
      associated transcript 1 are predictive of the development of CCC. These variants
      may be less efficient in down-regulating inflammatory responses and may
      contribute to the elevated production of proinflammatory cytokines in patients
      with CCC.

PMID- 16619188
TI  - Oral and intraperitoneal administration of phosphorothioate oligodeoxynucleotides
      leads to control of Cryptosporidium parvum infection in neonatal mice.
AB  - BACKGROUND: Neonates are particularly vulnerable to infections, in part because
      of the incomplete development of their immune system. Recent advances in
      immunostimulatory treatments based on conserved microbial components led us to
      assess the potential of oligodeoxynucleotides (ODNs) for decreasing the
      sensitivity of neonates to Cryptosporidium parvum infection. METHODS: Neonate
      mice were treated orally or intraperitoneally (ip) with CpG ODNs or non-CpG ODNs
      24 h before C. parvum infection, and parasite load and cytokine up-regulation
      were evaluated. RESULTS: CpG ODN 1668 and non-CpG ODN 1668 administered orally,
      as well as CpG ODN 1668 administered ip, induced an 80%-95% decrease in
      intestinal parasite load 6 days after infection. Intraperitoneal and oral
      pretreatment with CpG ODN 1668 led to a strong initial up-regulation of cytokines
      and CD69 messenger RNA in the intestine and a decrease in parasite load by a Toll
      like receptor 9 (TLR9)-dependent mechanism. By contrast, oral administration of
      non-CpG ODN 1668 decreased parasite load by a TLR9-independent mechanism.
      CONCLUSION: The control of neonatal C. parvum infection by ip or oral
      administration of ODNs is feasible by 2 different mechanisms: (1) the well-known
      interaction involving CpG/TLR9, leading to the production of cytokines and
      lymphocyte activation, and (2) a new unknown mechanism that is independent of
      TLR9 and effective orally.

PMID- 16619189
TI  - The influence of high-efficiency particulate air filtration on mortality and
      fungal infection among highly immunosuppressed patients: a systematic review.
AB  - BACKGROUND: Patients with hematological malignancies who are treated with
      intensive chemotherapy or who receive bone marrow transplants are exposed to an
      increased risk of developing nosocomial fungal infections. The aim of this
      systematic review was to compare the effectiveness of high-efficiency particulate
      air (HEPA) filtration with that of non-HEPA filtration in decreasing the rates of
      mortality and fungal infection among patients with diagnosed hematological
      malignancies and neutropenia or among patients with bone marrow transplants.
      METHODS: Articles identified in a Medline search, guidelines, and books, as well
      as the bibliographies of review articles, monographs, and the articles identified
      by Medline, were researched. Randomized trials and observational studies
      comparing HEPA filtration with conventional room ventilation were selected for
      inclusion in the present review. RESULTS: Sixteen trials (9 with death as an
      outcome and 10 with fungal infection as an outcome) that compared HEPA filtration
      with non-HEPA filtration were selected for meta-analyses. We discovered no
      significant advantages of HEPA filtration in the prevention of death among
      patients with hematological malignancies with severe neutropenia in randomized
      controlled trials (RCTs; relative risk [RR], 0.86 [95% confidence interval {CI},
      0.65-1.14]) and in studies of a lower standard (non-RCTs; RR, 0.87 [95% CI, 0.60
      1.25]). CONCLUSIONS: The placement in protected areas of patients with
      hematological malignancies with severe neutropenia or patients with bone marrow
      transplants appears to be beneficial, but no definitive conclusion could be drawn
      from the data available.

PMID- 16619190
TI  - Endogenous interleukin (IL)-1 alpha and IL-1 beta are crucial for host defense
      against disseminated candidiasis.
AB  - BACKGROUND: Interleukin (IL)-1 alpha and IL-1 beta are protective proinflammatory
      cytokines involved in host defense against Candida albicans. It is, however,
      unknown whether they provide protection through similar mechanisms. We
      investigated the effect of endogenous IL-1 alpha and IL-1 beta on disseminated C.
      albicans infection. METHODS: Mice deficient in the genes encoding IL-1 alpha (IL
      1 alpha-/-), IL-1 beta (IL-1 beta-/-), or both molecules (IL-1 alpha-/- beta-/-)
      were used. Survival and C. albicans outgrowth in the kidneys was assessed after
      intravenous injection of C. albicans. RESULTS: Both mortality and C. albicans
      outgrowth in the kidneys were significantly increased in IL-1 alpha-/- and IL-1
      beta-/- mice, compared with those in control mice, with the IL-1 alpha-/- beta-/-
      mice being most susceptible to disseminated candidiasis. The host defense
      mechanisms triggered by IL-1 alpha and IL-1 beta differed from one another. IL-1
      beta-/- mice showed decreased recruitment of granulocytes in response to an
      intraperitoneal C. albicans challenge, and generation of superoxide production
      was diminished in IL-1 beta-/- granulocytes. IL-1 alpha-/- mice had a reduced
      capacity to damage C. albicans pseudohyphae. Protective type 1 responses were
      deficient in both IL-1 alpha-/- and IL-1 beta-/- mice, as assessed by production
      of interferon-gamma by splenocytes in response to heat-killed C. albicans.
      CONCLUSION: Although IL-1 alpha and IL-1 beta have differential effects on the
      various arms of host defense, both cytokines are essential for mounting a
      protective host response against invasive C. albicans infection.

PMID- 16619191
TI  - Interaction of radiolabeled antibodies with fungal cells and components of the
      immune system in vitro and during radioimmunotherapy for experimental fungal
      infection.
AB  - BACKGROUND: The usefulness of radioimmunotherapy (RIT) for infectious diseases
      was recently demonstrated for several fungal and bacterial infections, but the
      mechanisms by which RIT is effective against microbes are uncertain. METHODS: We
      investigated the interaction between polysaccharide capsule-binding 18B7
      monoclonal antibodies (MAbs) labeled with alpha-emitter 213Bi and Cryptococcus
      neoformans cells as well as between 213Bi-18B7 and components of immune system,
      both in vitro and in vivo. RESULTS: For 213Bi-18B7, the microbicidal effect was
      predominantly due to "direct-hit" killing, with some contribution from the
      "crossfire" effect. The efficacy of cell killing correlated with the binding
      capacity of the MAb to the capsule and was dependent on the MAb isotype. RIT also
      promoted the apoptosis-like death of fungal cells. Cooperation was observed in
      vitro between the antifungal activity of macrophages and RIT, suggesting the
      potential for synergistic action in vivo. RIT was associated with changes in
      concentration of the cytokines interleukin (IL)-2, IL-4, IL-10, tumor necrosis
      factor-alpha, and interferon-gamma, suggesting that the therapeutic effects of
      RIT may result from changes in the inflammatory response. CONCLUSIONS: The
      present results suggest that the antimicrobial efficacy of RIT involves killing
      through promotion of fungal cell apoptosis-like death, reduction in yeast capsule
      size, cooperation with macrophages, and modulation of the inflammatory response.

PMID- 16619192
TI  - Virological response to highly active antiretroviral therapy is unaffected by
      antituberculosis therapy.
AB  - We compared 156 human immunodeficiency virus (HIV)-infected patients who had
      tuberculosis with control populations of similar size. Of 111 patients with HIV
      infection and tuberculosis who received highly active antiretroviral therapy
      (HAART) and therapy for tuberculosis concurrently, 92 (83%) achieved or
      maintained virus loads of <50 copies/mL, and 99 (89%) achieved or maintained a
      >or=2 log10 reduction in virus load after 6 months. Virological response and
      changes in CD4 cell count were equivalent to those in 111 matched HIV-infected
      subjects without tuberculosis starting HAART. Tuberculosis recurrence rates were
      similar to those found in an HIV-uninfected population of 156 subjects (3% and
      1%, respectively). Treatment for HIV and tuberculosis does not compromise
      outcomes for either disease.

PMID- 16619193
TI  - Independence of granzyme B secretion and interferon- gamma production during
      acute simian immunodeficiency virus infection.
AB  - BACKGROUND: Quantification of interferon (IFN)-gamma by enzyme-linked immunospot
      (ELISPOT) assay is currently used as a surrogate measurement of cytotoxic T
      lymphocyte (CTL) activity in nonhuman primates, particularly in simian
      immunodeficiency virus (SIV) models. Given that noncytotoxic cells and natural
      killer cells can also release IFN-gamma, quantification of granzyme B (GrB), a
      molecule secreted predominantly by activated CD8+ T cells, may represent an
      additional surrogate measurement of CTL activity. METHODS: We evaluated, by
      ELISPOT assay, GrB activity in response to 3 overlapping SIV Gag peptide pools in
      18 rhesus macaques with acute SIVmac251 infection and analyzed its correlation
      with IFN-gamma ELISPOT responses and plasma viral load. RESULTS: SIV Gag-specific
      GrB activity increased from 3.9- to 14.4-fold after infection, compared with that
      observed before infection. GrB secretion did not correlate directly with IFN
      gamma production. Importantly, SIV Gag-specific IFN- gamma production was
      negatively correlated with plasma viral load, whereas GrB activity was not.
      However, the peak of GrB activity coincided with the lowest plasma viral load
      detected after infection, whereas the magnitude of IFN-gamma production was 1.8
      fold lower than the GrB response; these results illustrate that the responses
      differ. CONCLUSION: Our data support the concept that the GrB and IFN-gamma
      ELISPOT assays measure immune responses in different immune-cell populations with
      unique specificities.

PMID- 16619194
TI  - Residual brain infection in relapsing-fever borreliosis.
AB  - BACKGROUND: Neurological involvement is common in the spirochetal infection
      relapsing fever (RF) in both humans and experimental animals. RF is best known
      for antigenic variation caused by the sequential expression of variable outer
      membrane lipoproteins of 2 sizes, variable small (Vsp) and variable large (Vlp)
      proteins. Less understood is the persistence of RF borreliae in the brain after
      they are cleared from the blood, referred to as residual brain infection (RBI).
      Our goal was to investigate the phenomenon of RBI in RF. METHODS: We studied RBI
      in immunocompetent mice by culturing blood and perfused brain samples 1 month
      after intraperitoneal inoculation with Borrelia turicatae serotype 1 (Bt1). Mice
      deficient in Toll-like receptor 2 (TLR2-/-) or in B and T cells (scid) were
      included for comparison. RESULTS: All scid mice had persistent infection in blood
      and brain. RBI was found in 3 (19%) of 16 immunocompetent and TLR2-/- mice. RBI
      was caused by either persistence of the original serotype (Bt1) or newly emerged
      Vsp (n=1, renamed Bt3) or Vlp serotypes. The Vsp of Bt1 (Vsp1) and Bt3 (Vsp3)
      were 75% identical. CONCLUSIONS: RBI in RF is relatively frequent and can occur
      by persistence of the original or newly emerged serotypes.

PMID- 16619195
TI  - Developmental regulation of Chlamydia trachomatis class I accessible protein-1, a
      CD8+ T cell antigen.
AB  - In this report, we show that the Chlamydia trachomatis-specific CD8+ T cell
      antigen class I accessible protein-1 (Cap1) is expressed during the early stages
      of the C. trachomatis developmental cycle. We provide additional evidence
      suggesting that Cap1 may be important in early immune recognition of the
      organism. Understanding the temporal and spatial expression of CD8+ T cell
      antigens such as Cap1 may be beneficial in designing multisubunit vaccines to
      stimulate a vigorous immune response against C. trachomatis.

PMID- 16619196
TI  - Reduced gene expression of intestinal alpha-defensins predicts diarrhea in a
      cohort of African adults.
AB  - BACKGROUND: Human defensin (HD) 5 and HD6, both Paneth cell alpha-defensins,
      contribute to the antimicrobial barrier against intestinal infection. We have
      previously demonstrated that levels of both HD5 and HD6 mRNA were reduced in
      adults living in urban Zambia, compared with those in adults living in London.
      The aim of the present study was to determine, during 2 years of follow-up,
      whether alpha-defensin expression in Zambian adults is related to susceptibility
      to diarrhea. METHODS: We analyzed intestinal biopsy samples from a longitudinal
      cohort study conducted in 83 Zambian adults by quantitative reverse-transcription
      polymerase chain reaction, Western blotting, immunohistochemistry, and in situ
      hybridization, and we measured the incidence of diarrhea. RESULTS: Levels of HD5
      and HD6 mRNA in Paneth cells varied between participants, over time, and
      seasonally and were strongly correlated with mucosal architecture. Gene
      expression was almost exclusively restricted to Paneth cells. The median
      (interquartile range) HD5 mRNA level was 6.0 (5.6-6.7) log10 transcripts/microg
      of total RNA among 18 participants who experienced diarrhea within 2 months after
      biopsy-sample collection, compared with 6.8 (6.2-7.3) log10 transcripts/microg of
      total RNA among 94 participants who did not (P=.006). A similar observation was
      made for HD6. CONCLUSIONS: These data indicate that intestinal alpha-defensin
      expression is dynamic and seasonal and suggest that susceptibility to intestinal
      infection is related to alpha-defensin expression.

PMID- 16619197
TI  - Presence or absence of cytomegalovirus in cerebrospinal fluid from patients with
      Guillain-Barre syndrome?

PMID- 16619199
TI  - A mathematical model investigating the impact of an environmental reservoir on
      the prevalence and control of vancomycin-resistant enterococci.

PMID- 16619200
TI  - On the efficient evaluation of Fourier patterns for nanoparticles and clusters.
AB  - Samples made of an isotropically oriented ensemble of atomic clusters or
      structures that are not large crystals (i.e. extended less than 10 periods in
      each direction) are at the frontier of today's material science and chemistry.
      Examples are nanoparticles, nanotubes, amorphous matter, polymers, and
      macromolecules in suspension. For such systems the computation of powder
      diffraction patterns (which may provide an efficient characterization) is to be
      performed the hard way, by summing contributions from each atom pair. This work
      deals with performing such computation in the most practical and efficient way.
      Three main points are developed: how to encode the enormous array of interatomic
      distances (which increase as the square or higher powers of the cluster diameter)
      to a much smaller array of equispaced values on a coarse grid (whose size
      increases linearly with the diameter); how to perform a fast computation of the
      diffraction pattern from this equispaced grid; how to optimize the grid step to
      obtain an arbitrarily small error on the computed diffraction pattern. Theory and
      examples are jointly developed and presented.

PMID- 16619202
TI  - del5p/dup5q in a 'cri du chat' patient without parental chromosomal
      rearrangement.

PMID- 16619203
TI  - A novel duplication/insertion mutation of NEFL in a patient with Charcot-Marie
      Tooth disease.

PMID- 16619204
TI  - Molecular cytogenetic analysis of a de novo interstitial chromosome 10q22
      deletion.
AB  - Interstitial deletions of 10q are rare, and only one patient with a deletion
      confined to chromosome band 10q22 has been reported so far. We report on a 2 6/12
      year-old girl with a constitutional interstitial deletion of one homologue of 10q
      [karyotype: 46,XX,del(10)(q22.2q22.3)de novo]. Our patient had muscular
      hypotonia, developmental delay, growth retardation, mild facial dysmorphism, and
      hypoplastic labia minora. The precise location and extent (3.6 Mb) of the
      deletion was determined by fluorescence in situ hybridization (FISH) using 16 YAC
      and BAC clones. The clinical features in our patient are remarkably similar to
      the previously reported patient with a 10q22.2 deletion.

PMID- 16619205
TI  - Letter re: fibula aplasia, tibial campomelia, and oligodactyly.

PMID- 16619206
TI  - Y-chromosome microdeletions in 45,X/46,XY patients.

PMID- 16619207
TI  - Congenital chylothorax in Opitz G/BBB syndrome.

PMID- 16619209
TI  - Letter from the Editor-in-Chief. Re: the Woo Suk Hwang articles in Science.

PMID- 16619210
TI  - Encapsulation of plant growth-promoting bacteria in alginate beads enriched with
      humic acid.
AB  - The key to achieving successful, reproducible results following the introduction
      of beneficial microbes into soil relies on the survival rate of the inoculated
      bacteria in a heterogeneous soil environment and hence an improved encapsulation
      method was developed. Owing to the constraints associated with the inoculum
      formulation, in this study, encapsulation of a plant growth promoting bacteria
      (PGPB) isolate Bacillus subtilis CC-pg104 was attempted with alginate by
      enriching the bead microenvironment with humic acid. High viability of the
      encapsulated bacteria was observed with minimum cell loss upon storage for 5
      months. Steady and constant cell release from the bead was observed for 1 week at
      different pH. Encapsulated cells remained active as evidenced by their ability to
      solubilize calcium phosphate in vitro. Successful plant growth promotion of
      lettuce by the encapsulated bacteria under gnotobiotic and sterile environment
      was also achieved. Feasibility of this improved encapsulation technique is mainly
      due to the dual benefits of humic acid to microbe and plant and its chemical
      properties allowing an easy mixing with alginate without interfering in the
      formation of the alginate gel beads by cross-linking with Ca2+ ions. Thus, the
      encapsulation method described in this study can be effectively used to protect
      the PGPB inoculum from adverse conditions of the soil for their successful
      establishment in the rhizosphere.

PMID- 16619212
TI  - Analysis of the maximum theoretical yield for the synthesis of erythromycin
      precursors in Escherichia coli.
AB  - The heterologous biosynthesis of complex polyketides in Escherichia coli was
      recently achieved through metabolic engineering. However, it was observed that
      less than 10% of the propionate carbon source is transformed into the
      erythromycin precursor, 6-deoxyerythronolide B (6dEB), resulting in a 1.4% molar
      yield. Therefore, metabolic flux analysis was performed using a model of the
      Escherichia coli metabolism with the addition of the enzymes required for 6dEB
      synthesis. The analysis shows that the maximum theoretical yield for 6dEB
      synthesis in E. coli is 11%. The maintenance energy requirement of E. coli and
      limitations in the specific oxygen uptake rate can further decrease the yield,
      suggesting that the observed 6dEB yield of 1.4% can be the result of these two
      factors. In addition, the results suggest that an increase in the specific carbon
      and oxygen uptake rates will increase the yield of 6dEB. The use of glucose as an
      alternative carbon source was also evaluated using metabolic flux analysis and
      the results suggest that the choice of glucose as the carbon source will allow a
      small improvement in performance relative to a propionate-based process.

PMID- 16619211
TI  - Cisplatin-induced hypomagnesemia and cardiac dysrhythmia.
AB  - We describe a case of a patient with cisplatin-induced hypomagnesemia who
      suffered brief asystole during an episode of gastroenteritis. Structural heart
      disease was excluded. The patient achieved complete clinical recovery after short
      term administration of intravenous magnesium supplementation. Cisplatin should be
      considered a cause of hypomagnesemic-related cardiac dysrhythmia. Magnesium
      deficit may increase myocardial electrical instability and thus, the risk of life
      threatening arrhythmias and sudden death. Long-term serum electrolyte measurement
      and appropriate replacement of magnesium are recommended.

PMID- 16619213
TI  - Confirmation of the origin of NISCH syndrome.
AB  - Neonatal ichthyosis-sclerosing cholangitis (NISCH) syndrome, a rare autosomal
      recessive ichthyosis syndrome characterized by scalp hypotrichosis, scarring
      alopecia, ichthyosis, and sclerosing cholangitis, was described for the first
      time in 2002. It is caused by a mutation in the gene coding for the tight
      junction protein claudin-1. Only four patients carrying the same mutation of the
      CLDN1 gene have been described until now. We report a patient presenting with the
      clinical characteristics of NISCH syndrome and carrying a novel mutation in the
      CLDN1 gene.

PMID- 16619214
TI  - Intronic alterations in BRCA1 and BRCA2: effect on mRNA splicing fidelity and
      expression.
AB  - Germline mutations in the human breast cancer susceptibility genes BRCA1 and
      BRCA2 account for the majority of hereditary breast and ovarian cancer. In spite
      of the large number of sequence variants identified in BRCA1 and BRCA2 mutation
      analyses, many of these genetic alterations are still classified as variants of
      unknown significance (VUS). In this study, we evaluated 12 BRCA1/2 intronic
      variants in order to differentiate their pathogenic or polymorphic effects on the
      mRNA splicing process. We detected the existence of aberrant splicing in three
      BRCA1 variants (c.301-2delA/IVS6-2delA, c.441+1G>A/IVS7+1G>A, and
      c.4986+6T>G/IVS16+6T>G) and two BRCA2 variants (c.8487+1G>A/IVS19+1G>A and c.8632
      2A>G/IVS20-2A>G). All but one of the aberrant transcripts arise from mutations
      affecting the conserved splice acceptor or donor sequences and all would be
      predicted to result in expression of truncated BRCA1 or BRCA2 proteins. However,
      we demonstrated that four of these splice-site mutations (i.e., c.301-2delA,
      c.441+1G>A, c.4986+6T>G, and c.8632-2A>G) with premature termination codons were
      highly unstable and were unlikely to encode for abundant expression of a mutant
      protein. Three variants of BRCA1 (c.212+3A>G/IVS5+3A>G, c.593+8A>G/IVS9+8A>G, and
      c.4986-20A>G/IVS16-20A>G) and four variants of BRCA2 (c.516-19C>T/IVS6-19C>T,
      c.7976-4_7976_3delTT/IVS17-4delTT, c.8487+19A>G/IVS19+19A>G, and c.9256-
      18C>A/IVS24- 18C>A) in our studies show no effects on the normal splicing
      process, and they are considered to be benign polymorphic alterations. Our
      studies help to clarify the aberrant splicing in BRCA1 and BRCA2 as well as
      provide information that can be used clinically to help counsel breast/ovarian
      cancer prone families.

PMID- 16619215
TI  - The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL
      cholesterol in a Caucasian population.
AB  - The genetic etiology of familial hypobetalipoproteinemia (FHBL) is unclear in the
      majority of cases. Mutations in apolipoprotein B (APOB) are the only confirmed
      causes of FHBL. Recently, loss-of-function mutations of PCSK9 gene have been
      shown to be associated with the hypocholesterolemia phenotype. Our primary goal
      was to confirm that mutations in PCSK9 could be another cause of FHBL. Using the
      sequencing approach, we found that the c.43_44insCTG variation in PCSK9, a common
      in-frame insertion in both African American and Caucasian populations, is
      associated with the hypocholesterolemia phenotype in three FHBL families. Then we
      tested whether this variation could be associated with lower cholesterol levels
      in the general population. A total of 403 subjects from a Caucasian population,
      in which hypobetalipoprotein (HBL) and normal groups were classified using
      standard criteria, were sequenced for this variation. The allele frequency of
      this variation in the HBL group was 0.186, but was only 0.128 in the normal lipid
      group. The mean plasma low-density lipoprotein (LDL)-cholesterol level in
      subjects heterozygous for this variant is significantly lower than that in the
      normal group (p<0.01). Heterozygous subjects also had higher high-density
      lipoprotein (HDL)-cholesterol levels (p<0.01). In general, LDL-cholesterol
      concentration in individuals with PCSK9 c.43_44insCTG variation was approximately
      10-15 mg/dL lower than that in normal individuals. We conclude that the
      c.43_44insCTG variant plays a role in lowering cholesterol in the general
      population.

PMID- 16619216
TI  - Hypermethylation of hMLH1, HPP1, p14(ARF), p16(INK4A) and APC in primary
      adenocarcinomas of the small bowel.
AB  - Small bowel adenocarcinoma (SB-AC) is a very rare tumor entity. Epigenetic
      alterations, including hypermethylation of DNA mismatch repair genes and tumor
      suppressor genes, seem to be important for carcinogenesis in tumors of the
      gastrointestinal tract, but have not yet been investigated in SB-AC. In the
      current study, the prevalence of hypermethylation in a panel of genes involved in
      gastrointestinal carcinogenesis (hMLH1, HPP1, p14(ARF), p16(INK4A), APC) was
      determined in a series of SB-AC. Paraffin-embedded tumor samples from 56 patients
      with SB-AC who underwent surgical resection between January 1985 and December
      2003 were investigated for hypermethylation by means of methylation-specific real
      time PCR, and compared with our findings in a previously investigated series of
      50 gastric adenocarcinomas. In comparison with adenocarcinomas of the stomach, SB
      AC revealed a significantly higher rate of hypermethylation of HPP1 (86% versus
      54%, p = 0.0003), p16(INK4A) (32% versus 10%, p = 0.0006), and a significantly
      lower rate of hypermethylation of APC (48% versus 84%, p = 0.0001).
      Hypermethylation of hMLH1 and p14(ARF) was present in 23% and 9% of SB-AC,
      respectively. Locally advanced tumor categories (pT3/4) showed a higher rate of
      hypermethylation of HPP1 (90%) than did early tumor categories (pT1/2 categories,
      40%; p = 0.0036). This was also reflected by the correlation between the HPP1
      hypermethylation and high UICC stage (p = 0.02). No correlation was found between
      hypermethylation and other clinicopathologic parameters such as age, tumor grade
      and nodal status. Our findings suggest that hypermethylation of hMLH1, HPP1,
      p16(INK4A) and APC is frequent in primary adenocarcinomas of the small bowel. The
      differences in the hypermethylation spectrum of small bowel and stomach cancer
      indicate significant epigenetic differences between these tumors.

PMID- 16619217
TI  - Visual inspection as a cervical cancer screening method in a primary health care
      setting in Africa.
AB  - We evaluated the feasibility and performance of visual inspection with acetic
      acid (VIA) and Lugol's iodine (VILI) for cervical cancer screening in a primary
      health-care setting in Kinshasa, Congo. Women (1,528) aged > or =30 years were
      screened independently by nurses and physicians by VIA and VILI and Pap cytology.
      Biopsy samples were obtained from women with abnormal colposcopies and from 290
      randomly chosen women with normal colposcopy. Cytological and histological
      examinations were performed in Lyon and Montreal, respectively. The prevalence of
      cervical intraepithelial neoplasia (CIN) of grades 1, 2 and 3 was 4.5, 1.3 and
      4%, respectively. Using biopsy as the reference, the sensitivity, specificity and
      negative predictive value (NPV) for > or =CIN 2 for VIA-nurse were 55.5% (95% CI:
      34.7-76.2), 64.6% (95% CI: 62.0-67.1) and 96.8% (95% CI: 93.5-98.7),
      respectively. The corresponding values for VILI-nurse were 44.0% (95% CI: 24.2
      63.8), 74.6% (95% CI: 72.3-76.9) and 96.7% (95% CI: 93.7-98.6). The equivalent
      parameters for physicians were 71.1% (95% CI: 46.7-95.5), 71.3% (95% CI: 68.9
      73.6) and 98.6% (95% CI: 96.0-99.7) for VIA and 68.3% (95% CI: 42.5-94.0), 76.2%
      (95% CI: 74.0-78.4) and 97.2% (95% CI: 95.3-98.5) for VILI. The sensitivity of
      cytology ranged between 31 and 72%, depending on the abnormality threshold used
      to define positivity, with a corresponding specificity range of 94-99% and a NPV
      range of 97-99%. Our results show that VIA and VILI performed by nurses and
      physicians are slightly more sensitive but less specific than Pap cytology across
      multiple combinations of test and lesion thresholds. Given their lower cost and
      easy deployment, visual inspection methods merit further assessment as cervical
      cancer screening methods for low-resource countries.

PMID- 16619218
TI  - Selective inhibition of Rab prenylation by a phosphonocarboxylate analogue of
      risedronate induces apoptosis, but not S-phase arrest, in human myeloma cells.
AB  - Bisphosphonates (BPs) are widely used in the treatment of osteolytic bone disease
      associated with multiple myeloma, and have been demonstrated to exert antitumor
      effects both in vitro and in vivo. However, the precise molecular mechanisms
      involved in the direct antitumor effects of BPs in vitro are not known. Nitrogen
      containing BPs, such as risedronate (RIS), act by inhibiting protein prenylation.
      A phosphonocarboxylate analogue of RIS, 3-PEHPC, has previously been shown in
      osteoclasts and macrophages to specifically inhibit prenylation of Rab GTPases.
      The aim of this study was to identify the molecular targets of RIS and 3-PEHPC in
      human myeloma cells and to determine the cellular effects of selective inhibition
      of Rab prenylation by 3-PEHPC as compared to nonspecific inhibition of protein
      prenylation by RIS in human myeloma cells. RIS dose-dependently inhibited
      prenylation of both Rap1A and Rab6, whereas 3-PEHPC only inhibited Rab6
      prenylation. Both RIS and 3-PEHPC dose-dependently increased apoptosis in human
      myeloma cells. RIS induced an accumulation of cells in the S-phase of the cell
      cycle, associated with inhibition of DNA replication. In contrast, 3-PEHPC did
      not cause cell-cycle arrest. Furthermore, geranylgeraniol could prevent
      inhibition of prenylation, induction of apoptosis, and cell-cycle arrest in
      response to RIS, but not inhibition of Rab prenylation and apoptosis induced by 3
      PEHPC, consistent with specific inhibition of Rab geranylgeranyl transferase by 3
      PEHPC. In conclusion, our studies demonstrate that selective inhibition of Rab
      prenylation induces apoptosis, but not S-phase arrest, thus identifying distinct
      molecular pathways that mediate the antimyeloma effect of nitrogen-containing
      BPs.

PMID- 16619219
TI  - Role of nitric oxide in heat shock protein induced apoptosis of gammadeltaT
      cells.
AB  - Activation induced cell death (AICD) has been proposed to serve as a mechanism to
      limit T lymphocyte proliferation induced by antigenic stimulation. Heat shock
      proteins (hsp60 and hsp70) expressed on oral tumor cells serve as ligands for
      peripheral blood gammadeltaT lymphocytes. Tumor cell lysis by gammadeltaT
      lymphocytes is mediated via recognition of hsp expressed on tumor cells. In the
      present study, we report that upon stimulation with hsp, gammadeltaT lymphocytes
      isolated from oral cancer patients undergo AICD as confirmed by DNA ploidy,
      annexin V staining and confocal microscopy. In cocultures of gammadeltaT
      lymphocytes and tumor cells, addition of antihsp60 and antihsp70 MAb, but not
      anti-Fas MAb (ZB4), inhibited DNA fragmentation of gammadeltaT lymphocytes. Flow
      cytometric analysis revealed a down regulation of Fas expression on gammadeltaT
      lymphocytes upon incubation with hsp60 and hsp70. Increased expression of iNOS
      was observed in hsp-stimulated gammadeltaT lymphocytes. Addition of monomethyl L
      arginine monoacetate, competitive inhibitor of NOS, inhibited nitric oxide (NO)
      production and apoptosis of gammadeltaT lymphocytes induced by hsp60 and hsp70.
      The NO-induced apoptosis of gammadeltaT lymphocytes involves activation of
      caspase-9 and loss of mitochondrial membrane potential. The present study
      explains a novel strategy adopted by tumor cells to evade immune recognition by
      gammadeltaT lymphocytes.

PMID- 16619220
TI  - Hemoglobin Hammersmith [beta42 (CD1) Phe --> Ser] in a Brazilian girl with
      congenital Heinz body hemolytic anemia.

PMID- 16619221
TI  - Prognostic factors in pleuro-pulmonary blastoma.
AB  - PURPOSE: To evaluate the prognostic factors in a series of children affected by
      pleuropulmonary blastoma (PPB). PATIENTS AND METHODS: Clinicopathological
      findings, treatment, and outcome of 22 PPB cases observed in 13 Italian
      Associations for Pediatric Hematology and Oncology centers are reported. Clinical
      data, surgical notes, pathologic findings, and summaries of treatment were taken
      from the charts and correlated with outcome by standard statistical methods.
      RESULTS: The series included 22 patients (14 males) with a median age of 30.5
      months followed up for a median of 22 months (range 2-176 months). In nine
      patients the PPB developed with lung involvement only. Congenital lung cysts were
      recorded in five cases. Nine patients had recurrences. Gender, side, tumor size,
      pre-existing lung cysts, and extent of surgical resection at diagnosis did not
      significantly affect survival by univariate analysis. Achieving total resection
      of the tumor at any time of treatment resulted in a significantly better
      prognosis (P = 0.01), whereas extrapulmonary involvement at diagnosis resulted in
      a significantly worse prognosis (P = 0.01). Estimated 15-year event-free and
      overall survival rates were 44 and 49% for all patients, respectively.
      CONCLUSIONS: PPB is an aggressive neoplasm. Total resection of PPB performed at
      any time of treatment appears to provide a better outcome, whereas extrapulmonary
      involvement at diagnosis worsens the prognosis.

PMID- 16619222
TI  - Sperm chemotaxis in marine invertebrates--molecules and mechanisms.
AB  - Sperm are attracted by chemical substances which are released by the egg. This
      process is called chemotaxis. Several molecules that are involved in chemotactic
      signaling of sperm from marine invertebrates are described and a model of the
      signaling pathway is presented. We discuss the motor response during chemotaxis
      and propose a model of the navigation strategy of sperm.

PMID- 16619223
TI  - The effect of acute pain crisis on exhaled nitric oxide levels in children with
      sickle cell disease.
AB  - Exhaled nitric oxide (FE(NO)) has been shown to be decreased in children with
      sickle cell disease. We sought to evaluate the effect of sickle cell vaso
      occlusive crisis (VOC) on FE(NO) levels. We measured FE(NO) levels in 42 children
      with sickle cell disease, 29 in their baseline health and 13 during an acute VOC.
      There was no difference in FE(NO) levels between children at baseline (15.12 +/-
      9.32 ppb) and those during an acute VOC (15.68 +/- 7.26 ppb; P = 0.794). FE(NO)
      is not a useful marker of acute VOC in children with sickle cell disease.

PMID- 16619224
TI  - Arp2/3 complex-mediated actin polymerisation occurs on specific pre-existing
      networks in cells and requires spatial restriction to sustain functional
      lamellipod extension.
AB  - The classical Arp2/3-mediated dendritic network defines the cytoskeleton at the
      leading edge of crawling cells, and it is generally assumed that Arp2/3-mediated
      actin polymerization generates the force necessary to extend lamellipods. Our
      previous work suggested that successful lamellipod extension required not only
      free barbed ends for actin polymerization but also a proper ultrastructural
      organization of the cytoskeleton. To further explore the structural role of the
      Arp2/3 complex-mediated networks in lamellipod morphology and function, we
      performed a detailed analysis of the ultrastructure of the Arp2/3-mediated
      networks, using the WA domains of Scar and WASp to generate mislocalised Arp2/3
      networks in vivo, and to reconstruct de novo Arp2/3-mediated actin nucleation and
      polymerization on extracted cytoskeletons. We present here evidence that
      spatially unrestricted Arp2/3-mediated networks are intrinsically three
      dimensional and multilayered by nature and, as such, cannot sustain significant
      polarized extension. Furthermore, such networks polymerize only at preferred
      locations in extracted cells, corresponding to pre-existing Arp2/3 networks,
      suggesting that the specific molecular organization of the actin cytoskeleton, in
      terms of structure and/or biochemical composition, dictates the location of
      Arp2/3 complex-mediated actin polymerization. We propose that successful
      lamellipod extension depends not only on localized actin polymerization mediated
      through local signalling, but also on spatial restriction of the Arp2/3 complex
      mediated nucleation of actin polymerization, both in terms of location within the
      cell and ultrastructural organization of the resulting network.

PMID- 16619225
TI  - Predictive value of the original content of CD34(+) cells for enrichment of
      hematopoietic progenitor cells from bone marrow harvests by the apheresis
      procedure.
AB  - We retrospectively investigated the feasibility of the apheresis procedure for
      red blood cell (RBC) reduction with a closed-bag system. We also sought to
      determine the optimal processing volume for the maximal recovery of hematopoietic
      progenitor cells (HPC). Twelve bone marrow (BM) harvests were processed for major
      ABO-incompatible allogeneic transplantation and one BM harvest was processed for
      autologous transplantation. The processing was performed through seven apheresis
      cycles with a two-bag system using COBE Spectra Version 6.1. The mean recovery
      rates were compared in the products after four cycles and seven cycles of BM
      processing. Mean cell recovery rates were 79.2% (67.6-97.5%) and 87.3% (68.9
      111.9%) for the mononuclear cells (MNC) and 84.5% (69.4-109.5%) and 92.0% (79.0
      107.7%) for the CD34(+) cells after four and seven cycles, respectively. A mean
      of 96.3% (93.0-98.1%) of the RBCs were finally removed. The yield of CD34(+)
      cells after seven cycles of processing (median: 10.35 x 10(7) cells) was 7.9%
      greater than that after four cycles of processing (median: 9.65 x 10(7) cells),
      exhibiting a less-than-significant enhancement in yield. The CD34(+) cell
      contents recovered in the concentrates up to four cycles (r = 0.989) and up to
      seven cycles (r = 0.993) were strongly correlated with the original content of
      the CD34(+) cells. Engraftment was obtained in all patients except one patient
      infused with purified CD34(+) cells. This latter result confirmed the
      hematopoietic potential of the cell populations recovered. Granulocyte recovery
      (defined as an absolute neutrophil cell count > or = 500/microL for a period of
      three consecutive days) ranged from 8 to 25 days (median: 16 days) post
      transplantation. No hemolytic reaction was observed in any of the patients. Our
      results confirmed the efficacy of BM processing cycles with the COBE Spectra
      device. However, we could not conclude that the large-volume apheresis for BM
      processing significantly enhanced the yields of HPC. The final recovery of
      CD34(+) cells after processing could be predicted from the CD34(+) cell content
      of the original collected marrow.

PMID- 16619226
TI  - The use of therapeutic plasmapheresis in the treatment of poisoned and snake bite
      victims: an academic emergency department's experiences.
AB  - The objective of this study is to describe the clinical status, procedural
      interventions, and outcomes of critically ill patients with poisoning and snake
      bite injuries presenting to a tertiary-care emergency department for treatment
      with therapeutic plasmapheresis. Records of 20 patients who presented to our
      academic emergency department over a 2-year period and who underwent
      plasmapheresis for poisoning or snake bite were retrospectively reviewed.
      Plasmapheresis was performed using centrifugation technology via an intravenous
      antecubital venous or subclavian vein catheter access. Human albumin or fresh
      frozen plasma were used as replacement fluids. Data extracted from the patient
      record included demographic data, clinical status, and outcome measures. Sixteen
      patients underwent plasmapheresis because of toxicity from snake bite. Three
      patients were treated for drug poisoning (phenytoin, theophylline, bipyridene
      HCl) and one patient for mushroom poisoning. Haematologic parameters such as
      platelet count, PT, and INR resolved rapidly in victims of snake bite injuries
      after treatment with plasmapheresis. Loss of limbs did not occur in these cases.
      Seven patients required admission to the intensive care unit. One patient with
      mushroom poisoning died. Mean length of hospital stay was 14.3 days (range 3-28
      days) for all cases. Plasmapheresis was a clinically effective and safe approach
      in the treatment of snake bite envenomation and other drug poisoning victims
      especially in the management of hematologic problems and in limb
      preservation/salvage strategies. In addition to established conventional
      therapies, emergency physicians should consider plasmapheresis among the
      therapeutic options in treatment strategies for selected toxicologic emergencies.

PMID- 16619227
TI  - Granulocyte transfusion therapy.

PMID- 16619228
TI  - The NHLBI Clinical Trials Network in transfusion medicine and hemostasis: an
      overview.
AB  - Transfusion Medicine is a broad discipline that affects the health care of
      patients from many medical disciplines. Despite the large impact of transfusion
      therapies on the management of patients with a variety of diseases, there are few
      clinical trials that evaluate the indications or the effectiveness of transfusion
      therapies. To respond to this need for better clinical data, the National Heart
      Lung and Blood Institute of the National Institutes of Health established a
      clinical trials network in Transfusion Medicine and Hemostasis. Following a
      competitive selection process, 17 university medical centers and a data
      coordinating center joined together to collaboratively address clinical questions
      in transfusion medicine and hemostasis. The activities, organization, and scope
      of the network is described below. Examples of clinical trials currently in the
      network "pipeline" are briefly summarized as an overview to more detailed
      presentations given elsewhere in this symposium.

PMID- 16619229
TI  - Extracorporeal photopheresis in children with graft-versus-host disease.
AB  - Acute and chronic graft-versus-host disease (GVHD) are major complications after
      allogeneic hematopoietic stem cell transplantation. Systemic corticosteroid is
      the first line of therapy but only half of the patients will respond. The
      management of steroid-refractory or steroid-dependent GVHD is challenging.
      Intensification of immunosuppression has been the main strategy but the response
      rate is not satisfactory. Furthermore, the incidence of treatment-related
      toxicity and opportunistic infection is unacceptably high. Extracorporel
      photopheresis (ECP) has been used in the management of refractory GVHD.
      Retrospective analysis of the experience in adult patients showed activity in
      both acute and chronic GVHD. The procedure was well tolerated with minimal
      changes in the hematologic and biochemical parameters. However the machine
      currently approved is designed for patients over 40 kg of body weight.
      Significant fluid shift and venous access are major concerns when ECP is
      performed in children. Various modifications of the ECP procedure have been tried
      to manage patients with low body weight. Experience with ECP in children is
      limited but preliminary data also showed favorable response in children with
      resistant GVHD. Further investigations are needed to refine the optimal schedule,
      duration, and treatment technique for pediatric patients.

PMID- 16619230
TI  - Photopheresis in solid organ transplant rejection.
AB  - Photopheresis has become a key component in the therapeutic armamentarium of
      cutaneous T-cell lymphoma, graft-versus-host disease following stem cell
      transplant, and allograft rejection of solid organs such as heart. Although it is
      considered a new treatment modality in its present form, the field of
      phototherapy dates back thousands of years. In this review, the reader will learn
      more about the history of photopheresis and how it became a therapeutic
      alternative for patients with solid organ transplants. An extensive literature
      search will highlight the evidence-based benefits of photopheresis (or lack
      thereof). A discussion of the mechanism of action of photopheresis and the
      technical aspects of the procedure will also be covered. Since photopheresis may
      be the best tolerated form of immunomodulation, current promising, albeit
      preliminary data on its efficacy warrant further investigation and understanding.

PMID- 16619231
TI  - Background, rationale, and design of a clinical trial to assess the effects of
      platelet dose on bleeding risk in thrombocytopenic patients.
AB  - Outlined is the background and rationale for the initiation of a randomized
      prospective platelet transfusion trial to evaluate the effects of platelet dose
      on hemostasis and platelet utilization rates. This clinical trial is being
      performed by the newly established Transfusion Medicine/Hemostasis Clinical Trial
      Network supported by the National Heart, Lung, and Blood Institute of the
      National Institutes of Health. The trial will randomize 1,350 patients into three
      platelet transfusion arms based on body surface area (BSA). The lower dose will
      be 1.1 x 10(11) platelets/m(2), the medium dose will be 2.2 x 10(11)
      platelets/m(2), and the higher dose will be 4.4 x 10(11) platelets/m(2). The
      primary outcome measure will be the incidence of Grade 2 bleeding; i.e., gross
      hemorrhage without the need for red cell transfusion. Major secondary outcome
      measures will be the total number of platelets transfused, the total number of
      platelet transfusion events, the highest grade of bleeding, and bleeding
      severity. It is expected that this clinical trial will change platelet
      transfusion practice by identifying whether low-dose platelet transfusion therapy
      provides adequate hemostasis and what is the most cost-effective strategy for
      providing platelet transfusions.

PMID- 16619232
TI  - Rituximab therapy for thrombotic thrombocytopenic purpura: a proposed study of
      the Transfusion Medicine/Hemostasis Clinical Trials Network with a systematic
      review of rituximab therapy for immune-mediated disorders.
AB  - The rationale for immunosuppressive therapy of thrombotic thrombocytopenic
      purpura (TTP) was established by observations that TTP may be caused by
      autoantibodies to ADAMTS13. Patients with high-titer autoantibodies to ADAMTS13
      may have a higher mortality, and survivors may require prolonged plasma exchange
      therapy in spite of adjunctive glucocorticoid treatment. More intensive
      immunosuppressive therapy with rituximab may provide benefit for many of these
      patients. The Transfusion Medicine/Hemostasis Clinical Trials Network is
      developing a randomized, clinical trial to test the hypothesis that addition of
      rituximab to standard treatment of TTP with plasma exchange and glucocorticoids
      will decrease initial treatment failure rates as well as subsequent relapses over
      the following 3 years. To provide the background data for this clinical trial, a
      systematic review of all published reports on rituximab treatment of immune
      mediated disorders was performed. Twelve articles have reported 27 patients
      treated with rituximab for TTP, with benefit described in 25 (93%) of the
      patients. Additional reports have described rituximab treatment of 37 other
      immune-mediated disorders, with clinical response in most patients. These
      observations from small uncontrolled case series provide the background and
      rationale for a randomized clinical trial to establish the role of rituximab in
      the management of patients with TTP.

PMID- 16619233
TI  - Anti-apoptotic factor humanin is expressed in the testis and prevents cell-death
      in leydig cells during the first wave of spermatogenesis.
AB  - Humanin (HN) is a 24 amino acids peptide with potent neuro-survival properties
      that protects against damage associated with Alzheimer's disease. In the present
      report, we have demonstrated by immunohistochemical analysis and Western blotting
      the pattern of expression of rat humanin (HNr) in the testis of 10- to 60-day-old
      rats. The Leydig cells of 10- and 40- day-old rats expressed this peptide at high
      levels; and in the testis of 60-day-old rats the expression of HNr expanded to
      include Leydig, endothelial, peritubular and germ cells. As monitored by Western
      blotting, HNr was released into the medium of cultures of Leydig cells isolated
      from 10-, 40-, and 60-days-old rats. HNr stimulated the incorporation of
      [(3)H]TdR into DNA of Leydig cells from 10-days-old rats, in a manner that
      indicated promotion of cell survival rather than an increase in the rate of cell
      multiplication. This peptide also enhanced steroidogenesis by cultured Leydig
      cells from 10- to 40-day-old rats both alone and synergistically with IGF-I. The
      expression of HNr in cultured Leydig cells increased in response to GH and IGF-I.
      In summary, we demonstrated here that HNr was expressed at all stages of
      maturation in the rat testis. This peptide promoted the survival of Leydig cells
      in culture and interacted with IGF-I to stimulate DNA synthesis and
      steroidogenesis. We propose that HNr is a novel testicular anti-apoptotic factor.

PMID- 16619234
TI  - Human subcutaneous adipose cells support complete differentiation but not self
      renewal of hematopoietic progenitors.
AB  - Adipose tissue is now considered as an endocrine organ implicated in energy
      regulation, inflammation and immune response, and as a source of multipotent
      cells with a broad range of differentiation capacities. Some of these cells are
      of a mesenchymal type which can -- like their bone marrow (BM) counterpart --
      support hematopoiesis, since in a previous study we were able to reconstitute
      lethally irradiated mice by cells isolated from adipose tissue. In the present
      study, we established that cells derived from the stroma-vascular fraction of
      human subcutaneous fat pads support the complete differentiation of hematopoietic
      progenitors into myeloid and B lymphoid cells. However, these cells are unable to
      maintain the survival and self-renewal of hematopoietic stem cells. These
      features, similar to those of BM adipocytes, are the opposite of those of other
      cell types derived from mesenchymal progenitors such as BM myofibroblasts or
      osteoblasts. Because it is abundant and accessible, adipose tissue could be a
      convenient source of cells for the short-term reconstitution of hematopoiesis in
      man.

PMID- 16619235
TI  - Double-strand DNA break repair with replication slippage on two strands: a novel
      mechanism of deletion formation.
AB  - We have characterized an unusual family with two different androgen receptor (AR)
      gene deletions, in which we propose a novel mechanism of deletion formation has
      occurred. Affected individuals have the X-linked disorder androgen insensitivity
      syndrome, and we previously showed that different family members have deletions
      of different exons of the AR gene. We have now fully sequenced the deletions from
      affected individuals, and confirmed the presence of different deletions in
      different affected family members. Most affected and heterozygote individuals
      have a 4,430-bp deletion of exon 5 that occurred between repeated GTGGCAT motifs
      in introns 4 and 5. One affected hemizygous individual has a 4,033-bp deletion of
      exons 6 and 7 that occurred between repeated CCTC motifs in introns 5 and 7. The
      intron 5 breakpoint junctions of the two deletions are only 11 bp apart.
      Surprisingly, the maternal grandmother of the original index case was found to be
      mosaic for both deletional events, as well as having the normal AR gene.
      Karyotyping ruled out 47,XXX trisomy, indicating triple mosaicism for the two
      different deleted AR alleles and a normal AR allele. This triple mosaicism must
      have occurred early in embryonic development, as both deletions were passed on to
      different children. Based on these findings, we propose a novel mechanism of
      deletion formation. We suggest that during AR gene replication, a double strand
      DNA break occurred in intron 5, and that a variant of replication slippage
      occurred on both newly synthesized strands between the repeat motifs of
      microhomology, leading to the formation of the two different AR gene deletions.

PMID- 16619236
TI  - Hydralazine rescues PC12 cells from acrolein-mediated death.
AB  - Acrolein, a major lipid peroxidation product, has been associated with both CNS
      trauma and neurodegenerative diseases. Because of its long half-life, acrolein is
      a potent endogenous toxin capable of killing healthy cells during the secondary
      injury process. Traditionally, attempts to intervene in the process of
      progressive cell death after the primary injury have included scavenging reactive
      oxygen species (so-called free radicals). The animal data supporting such an
      approach have generally been positive, but all human clinical trials attempting a
      similar outcome in human CNS injury have failed. New drugs that might reduce
      toxicity by scavenging the products of lipid peroxidation present a promising,
      and little investigated, therapeutic approach. Hydralazine, a well-known
      treatment for hypertension, has been reported to react with acrolein, forming
      hydrazone in cell-free systems. In the companion paper, we have established an
      acrolein-mediated cell injury model using PC12 cells in vitro. Here we test the
      hypothesis that the formation of hydrazone adducts with acrolein is able to
      reduce acrolein toxicity and spare a significant percentage of the population of
      PC12 cells from death. Concentrations of approximately 1 mM of this aldehyde
      scavenger can rescue over 80% of the population of PC12 cells. This study
      provides a basis for a new pharmacological treatment to reduce the effects of
      secondary injury in the damaged and/or diseased nervous system. In particular, we
      describe the need for new drugs that possess aldehyde scavenging properties but
      do not interfere with the regulation of blood pressure.

PMID- 16619237
TI  - Is prostaglandin E(2) a pathogenic factor in amyotrophic lateral sclerosis?
AB  - OBJECTIVE: To elucidate the role of cyclooxygenase-1 (Cox1) and prostaglandin
      E(2) in ALS neurodegeneration. METHODS: Mutation in superoxide dismutase-1 is a
      cause of the fatal paralytic disorder amyotrophic lateral sclerosis. Inhibition
      of cyclooxygenase-2 (Cox-2) in transgenic mice expressing an amyotrophic lateral
      sclerosis-linked superoxide dismutase-1 mutation led to the idea that
      prostaglandin E(2), the main synthetic product of Cox-2, is pathogenic in
      amyotrophic lateral sclerosis. RESULTS: Herein, we show by genetic intervention
      that prostaglandin E(2) in the spinal cord is mainly produced by Cox-1, and that
      ablation of Cox-1 fails to attenuate neurodegeneration. INTERPRETATION: The
      previously documented role of Cox-2 in ALS neurodegeneration in this particular
      mouse model occurs through a mechanism independent of prostaglandin E(2).
      Furthermore, plans to use selective Cox-1 inhibitors for neuroprotection in ALS
      are unlikely to be fruitful.

PMID- 16619238
TI  - Acrolein-mediated mechanisms of neuronal death.
AB  - It is well known that traumatic injury in the central nervous system can be
      viewed as a primary injury and a secondary injury. Increases in oxidative stress
      lead to breakdown of membrane lipids (lipid peroxidation) during secondary
      injury. Acrolein, an alpha,beta-unsaturated aldehyde, together with other
      aldehydes, increases as a result of self-propagating lipid peroxidation.
      Historically, most research on the pathology of secondary injury has focused on
      reactive oxygen species (ROS) rather than lipid peroxidation products. Little is
      known about the toxicology and cell death mediated by these aldehydes. In this
      study, we investigated and characterized certain features of cell death induced
      by acrolein on PC12 cells as well as cells from dorsal root ganglion (DRG) and
      sympathetic ganglion in vitro. In the companion paper, we evaluated a possible
      means to interfere with this toxicity by application of a compound that can bind
      to and inactivate acrolein. Here we use both light and atomic force microscopy to
      study cell morphology after exposure to acrolein. Administration of 100 microM
      acrolein caused a dramatic change in cell morphology as early as 4 hr.
      Cytoskeletal structures significantly deteriorated after exposure to 100 microM
      acrolein as demonstrated by fluorescence microscopy, whereas calpain activity
      increased significantly at this concentration. Cell viability assays indicated
      significant cell death with 100 microM acrolein by 4 hr. Caspase 3 activity and
      DNA fragmentation assays were performed and supported the notion that 100 microM
      acrolein induced PC12 cell death by the mechanism of necrosis, not apoptosis.

PMID- 16619240
TI  - Degradation of insulin-like growth factor-I receptor occurs via ubiquitin
      proteasome pathway in human lung cancer cells.
AB  - Insulin-like growth factor-I receptor (IGF-IR) is often overexpressed in
      malignant tumors, and is involved in the establishment and maintenance of
      malignant phenotypes. Tyrosine kinase receptor endocytosis is commonly triggered
      by ligand binding and occurs via clathrin-coated vescicles that transfer the
      receptor to the lysosome system for degradation. Our study aims at the evaluation
      of the mechanisms involved in IGF-IR downregulation in neoplastic (Npl) and non
      neoplastic (non-Npl) cells. Exposure to insulin-like growth factor-I (IGF-I) of
      human lung adenocarcinoma cell lines (A549 and H1299) triggers IGF-IR
      ubiquitination and internalization processes that require energy and are preceded
      by the phosphorylation of receptor tyrosines. Differently from other plasma
      membrane substrates of the ubiquitin system, IGF-IR is degraded mostly by the
      proteasome in these tumor cell lines. The degradation is inhibited by lactacystin
      and unaffected by lysosomal inhibitors such as bafilomycin A1 and NH(4)Cl. IGF-IR
      is processed in a similar manner also in fresh specimens of human lung tumors,
      while it requires active lysosomal functions in non-Npl human lung tissues. These
      results suggest that the degradation routes of ubiquitinated IGF-IR diverge in
      normal and Npl cells, and further support the involvement of IGF-IR signaling in
      cancer. Such a different route for IGF-IR processing might take place sometime
      during development, since both proteasome and lysosome pathways are active in
      fetal lung human fibroblasts, IMR90 cells.

PMID- 16619239
TI  - Long-range PCR facilitates the identification of PMS2-specific mutations.
AB  - Mutations within the DNA mismatch repair gene, "postmeiotic segregation increased
      2" (PMS2), have been associated with a predisposition to hereditary nonpolyposis
      colorectal cancer (HNPCC; Lynch syndrome). The presence of a large family of
      highly homologous PMS2 pseudogenes has made previous attempts to sequence PMS2
      very difficult. Here, we describe a novel method that utilizes long-range PCR as
      a way to preferentially amplify PMS2 and not the pseudogenes. A second, exon
      specific, amplification from diluted long-range products enables us to obtain a
      clean sequence that shows no evidence of pseudogene contamination. This method
      has been used to screen a cohort of patients whose tumors were negative for the
      PMS2 protein by immunohistochemistry and had not shown any mutations within the
      MLH1 gene. Sequencing of the PMS2 gene from 30 colorectal and 11 endometrial
      cancer patients identified 10 novel sequence changes as well as 17 sequence
      changes that had previously been identified. In total, putative pathologic
      mutations were detected in 11 of the 41 families. Among these were five novel
      mutations, c.705+1G>T, c.736_741del6ins11, c.862_863del, c.1688G>T, and c.2007
      1G>A. We conclude that PMS2 mutation detection in selected Lynch syndrome and
      Lynch syndrome-like patients is both feasible and desirable.

PMID- 16619241
TI  - FHL2 interacts with both ADAM-17 and the cytoskeleton and regulates ADAM-17
      localization and activity.
AB  - ADAM-17 is a metalloprotease-disintegrin responsible for the ectodomain shedding
      of several transmembrane proteins. Using the yeast two-hybrid system, we showed
      that ADAM-17 interacts with the Four and Half LIM domain 2 protein (FHL2), a LIM
      domain protein that is involved in multiple protein-protein interaction. We
      demonstrated that this interaction involved the amino-acid sequence of ADAM-17
      from position 721 to739. In the cardiomyoblast cells H9C2, ADAM-17 and FHL2
      colocalize with the actin-based cytoskeleton and we showed that FHL2 binds both
      ADAM-17 and the actin-based cytoskeleton. We found that mainly the mature form of
      ADAM-17 associates with the cytoskeleton, although the maturation of ADAM-17 by
      furin is not necessary for its binding to the cytoskeleton. Interestingly, less
      ADAM-17 was detected at the surface of wild-type mouse macrophages compared to
      FHL2 deficient macrophages. However, wild-type cells have a higher ability to
      release ADAM-17 substrates under PMA stimulation. Altogether, these results
      demonstrate a physical and functional interaction between ADAM-17 and FHL2 that
      implies that FHL2 has a role in the regulation of ADAM-17.

PMID- 16619242
TI  - The evolution of immune mechanisms.
AB  - From early on in evolution, organisms have had to protect themselves from
      pathogens. Mechanisms for discriminating "self" from "non-self" evolved to
      accomplish this task, launching a long history of host-pathogen co-evolution.
      Evolution of mechanisms of immune defense has resulted in a variety of
      strategies. Even unicellular organisms have rich arsenals of mechanisms for
      protection, such as restriction endonucleases, antimicrobial peptides, and RNA
      interference. In multicellular organisms, specialized immune cells have evolved,
      capable of recognition, phagocytosis, and killing of foreign cells as well as
      removing their own cells changed by damage, senescence, infection, or cancer.
      Additional humoral factors, such as the complement cascade, have developed that
      co-operate with cellular immunity in fighting infection and maintaining
      homeostasis. Defensive mechanisms based on germline-encoded receptors constitute
      a system known as innate immunity. In jaw vertebrates, this system is
      supplemented with a second system, adaptive immunity, which in contrast to innate
      immunity is based on diversification of immune receptors and on immunological
      memory in each individual.Usually, each newly evolved defense mechanism did not
      replace the previous one, but supplemented it, resulting in a layered structure
      of the immune system. The immune system is not one system but rather a
      sophisticated network of various defensive mechanisms operating on different
      levels, ranging from mechanisms common for every cell in the body to specialized
      immune cells and responses at the level of the whole organism. Adaptive changes
      in pathogens have shaped the evolution of the immune system at all levels.

PMID- 16619243
TI  - Optimization and evaluation of single-cell whole-genome multiple displacement
      amplification.
AB  - The scarcity of genomic DNA can be a limiting factor in some fields of genetic
      research. One of the methods developed to overcome this difficulty is whole
      genome amplification (WGA). Recently, multiple displacement amplification (MDA)
      has proved very efficient in the WGA of small DNA samples and pools of cells, the
      reaction being catalyzed by the phi29 or the Bst DNA polymerases. The aim of the
      present study was to develop a reliable, efficient, and fast protocol for MDA at
      the single-cell level. We first compared the efficiency of phi29 and Bst
      polymerases on DNA samples and single cells. The phi29 polymerase generated
      accurately, in a short time and from a single cell, sufficient DNA for a large
      set of tests, whereas the Bst enzyme showed a low efficiency and a high error
      rate. A single-cell protocol was optimized using the phi29 polymerase and was
      evaluated on 60 single cells; the DNA obtained DNA was assessed by 22 locus
      specific PCRs. This new protocol can be useful for many applications involving
      minute quantities of starting material, such as forensic DNA analysis, prenatal
      and preimplantation genetic diagnosis, or cancer research.

PMID- 16619244
TI  - Contrasting behaviors of mutant cystathionine beta-synthase enzymes associated
      with pyridoxine response.
AB  - Cystathionine beta-synthase (CBS) deficiency is a recessive genetic disorder
      characterized by extremely elevated levels in plasma homocysteine. Patients
      homozygous for the I278T or R266K mutations respond clinically to pharmacologic
      doses of pyridoxine, the precursor of a cofactor for the enzyme, 5'-pyridoxal
      phosphate (PLP). Here we test the hypothesis that these mutations are pyridoxine
      responsive because they lower the affinity of the enzyme for PLP. We show that
      recombinant R266K has 30 to 100% of the specific activity of the wild-type
      enzyme, while I278T only has only 1 to 5% activity. Kinetic studies show that the
      decreased activity in both enzymes is due to reduced turnover rate and not
      substrate binding. Neither I278T nor R266K appear to greatly affect multimer
      status of the enzyme. The R266K enzyme has reduced affinity for PLP compared to
      the wild-type enzyme, providing a mechanism for the pyridoxine response observed
      in patients. Surprisingly, the I278T enzyme does not have altered affinity for
      PLP. To confirm that this was not an in vitro artifact, we examined pyridoxine
      response in mice that stably express human I278T as their sole source of CBS
      activity. These mice have extremely elevated plasma homocysteine levels and do
      not respond significantly to large doses of pyridoxine. Our findings suggest that
      there may be multiple mechanisms involved in response to pyridoxine.

PMID- 16619245
TI  - Ascidian neural crest-like cells: phylogenetic distribution, relationship to
      larval complexity, and pigment cell fate.
AB  - Migratory neural crest-like cells, which express the cell surface antigen HNK-1
      and develop into pigment cells, have recently been identified in the ascidian
      Ecteinascidia turbinata. Here we use HNK-1 expression as a marker to determine
      whether neural crest-like cells are responsible for pigment development in
      diverse ascidian species. We surveyed HNK-1 expression and tyrosinase activity in
      12 ascidian species, including those with different adult organizations,
      developmental modes, and larval sizes and complexities. We observed HNK-1
      positive cells in every species, although the timing of HNK-1 expression varied
      according to the extent of larval complexity. HNK-1 expression was initiated
      during the late tailbud stage in species in which adult features are formed
      precociously in large complex larvae. In contrast, HNK-1 positive cells did not
      appear until the swimming tadpole or juvenile stage in species with small simple
      larvae in which most adult features appear after metamorphosis. Double labeling
      experiments indicated that HNK-1 and tyrosinase are expressed in the same subset
      of pigment-forming mesenchymal cells in species with complex or simple larvae. In
      addition, the absence of HNK-1 and tyrosinase expression in albino morphs of the
      colonial ascidian Botryllus schlosseri suggested that the major fate of neural
      crest-like cells is to become pigment cells. The results suggest that ascidian
      neural crest-like cells and vertebrate neural crest cells had a common origin
      during chordate evolution and that their primitive function was to generate body
      pigmentation.

PMID- 16619246
TI  - Evolution of the vertebrate ParaHox clusters.
AB  - The ParaHox cluster contains three Hox-related homeobox genes. The evolution of
      this sister of the Hox-gene clusters has been studied extensively in metazoans
      with a focus on its early evolution. Its fate within the vertebrate lineage, and
      in particular following the teleost-specific genome duplication, however, has not
      received much attention. Three of the four human ParaHox loci are linked with
      PDGFR family tyrosine kinases. We demonstrate that these loci arose as
      duplications in an ancestral vertebrate and trace the subsequent history of gene
      losses. Surprisingly, teleost fishes have not expanded their ParaHox repertoire
      following the teleost-specific genome duplication, while duplicates of the
      associated tyrosine kinases have survived, supporting the hypothesis of a large
      scale duplication followed by extensive gene loss.

PMID- 16619247
TI  - Molecular profiling of platinum resistant ovarian cancer: use of the model in
      clinical practice.

PMID- 16619249
TI  - In vivo expression of survivin and its splice variant survivin-2B: impact on
      clinical outcome in acute myeloid leukemia.
AB  - Survivin, a member of the inhibitor of apoptosis protein family, is expressed in
      most human cancers, but undetectable in normal differentiated adult tissue in
      vivo. Because of this cancer-related expression, survivin is a promising target
      for cancer therapy. To determine the expression and prognostic role of survivin
      in acute myeloid leukemia (AML), we investigated the mRNA expression pattern of
      survivin and of the splice variants survivin-2B and survivin-DeltaEx3 in adult (n
      = 74) and children (n = 31) with de novo AML using RT-PCR. Survivin was the
      predominant transcript variant in AML cells, whereas significantly lower levels
      of survivin-2B and survivin-DeltaEx3 were observed (p < or = 0.0001). Neither
      expression of survivin nor of any splice variant correlated with maturation stage
      (FAB subtypes, immunophenotype) or cytogenetic risk groups. For AML cases treated
      according to AMLCG92 (adult) and AML-BFM93 (children) protocols, respectively,
      expression patterns were correlated with clinical data: in adult AML (n = 51),
      low expression of survivin-2B correlated with a better overall survival (p =
      0.05; mean survival time 19 months vs. 9 months) and a better eventfree survival
      (p < or = 0.01; 27 months vs. 10 months). In childhood AML (n = 31), high
      survivin-DeltaEx3 expression was associated with a shorter overall survival (p <
      or = 0.05; 24 months vs. 43 months). We conclude that certain survivin splice
      variants have potential prognostic impact for long-term therapy outcome in adult
      as well as childhood de novo AML.

PMID- 16619250
TI  - Human discs large and scrib are localized at the same regions in colon mucosa and
      changes in their expression patterns are correlated with loss of tissue
      architecture during malignant progression.
AB  - Loss of cell polarity is one of the hallmarks of malignant carcinomas. Most of
      the understanding about the link between cell polarity and proliferation control
      comes from studies on the Drosophila tumor suppressors discs large (Dlg),
      scribble (Scrib) and lethal giant larvae (lgl). Mammalian homologues of these
      proteins have been described and are conserved in sequence and function. Human
      Dlg (hDlg) and Scrib were independently shown to be down-regulated during
      malignant progression. This, and other lines of evidence, points toward the
      participation of both hDlg and hScrib in a common pathway involved in polarity
      control and tumor suppression. We investigated the correlation between the
      expression of both proteins in tissues and their relative contributions to the
      maintenance of tissue architecture during colon cancer development. We analyzed
      the levels and distribution of hDlg and hScrib by immunohistochemistry, using
      serial sections of the same sample. We used normal and neoplastic colon mucosa,
      since it offers a good model for analyzing these features in progressive
      dysplastic stages. The results demonstrate that both proteins localize at the
      same regions in polarized colon epithelia, and that in normal samples the
      proteins' distribution varies as cells differentiate at the surface mucosa. In
      neoplasia, alterations in the expression pattern of hDlg and of hScrib increase
      during tumor progression; down-regulation of both proteins being associated with
      lack of epithelial cell polarity and disorganized tissue architecture. The
      results, therefore, demonstrate that there is an inverse relationship between the
      levels of hDlg and hScrib expression and the loss of cell polarity and tissue
      architecture in the colon.

PMID- 16619251
TI  - RASSF1A hypermethylation and its inverse correlation with BRAF and/or KRAS
      mutations in MSI-associated endometrial carcinoma.
AB  - Both hypermethylation of the tumor suppressor gene RASSF1A and activating
      mutations of the KRAS and/or BRAF gene have been reported in a variety of human
      cancers. To investigate these epigenetic and genetic alterations in endometrial
      carcinoma (EC), we examined their frequency in 4 uterine EC cell lines and in 75
      sporadic primary ECs. Using methylation specific PCR, we found RASSF1A
      methylation in 25 of 75 (33.3%) ECs. RASSF1A methylation was significantly
      associated with microsatellite instability (MSI, p < 0.001) and also with hMLH1
      methylation (p < 0.001). KRAS mutations were detected in 14 of 75 (18.7%) ECs.
      BRAF mutations were identified in only 3 of 75 (4.0%) ECs and were not found in
      ECs with KRAS mutations or RASSF1A methylation. RASSF1A methylation was more
      frequent in KRAS mutation-negative ECs than in KRAS mutation-positive ECs (37.7%
      vs 14.3%), but this inverse correlation is not statistically significant (p =
      0.122). However, we observed that RASSF1A methylation was inversely correlated
      with KRAS and/or BRAF mutations (p = 0.028) in MSI-negative ECs, while this
      inverse correlation disappeared in MSI-positive ECs. Furthermore, in MSI-positive
      ECs, 2 cases of concomitant RASSF1A methylation and KRAS mutation were found.
      Taken together, these results provide strong evidence that, in EC tumorigenesis,
      RASSF1A promoter hypermethylation is as important as KRAS mutations in activating
      the RAS pathway.

PMID- 16619252
TI  - Differing molecular pathology of pancreatic adenocarcinoma in Egyptian and United
      States patients.
AB  - Variations in genetic mutations in pancreatic carcinoma between different
      populations have not been studied extensively, especially in developing countries
      where pancreatic cancer is rare. We studied the molecular pathology of 44
      pancreatic carcinomas from patients residing in a heavily polluted region in the
      Nile River delta and compared the findings with tumors from 44 United States (US)
      patients. We evaluated K-ras mutations in codon 12, p53 mutations in exons 5-8,
      and Gadd45a mutations in exons 1 and 4. Overall, rates of K-ras, p53 and Gadd45
      mutations were not statistically different in tumors of patients from Egypt and
      the US (67.4 vs. 63.4%; 27.3 vs. 36.4% and 9.1 vs. 4.5%, respectively). However,
      there were distinct differences in the specific types of K-ras and p53 mutations
      between the 2 groups. In K-ras, G --> T transversion mutation was more frequent
      in the tumors from Egypt than from the US (58.6 vs. 26.9%), whereas G --> C
      transversion was detected in 26.9% of US tumors but none from Egypt (p = 0.003).
      We also found a trend toward differences in the p53 exons in which mutations
      occurred, with higher frequency of exon 5 mutation and lower frequency of exon 6
      mutation in Egyptian tumors. Logistic regression showed that K-ras G --> T
      transversion mutations and p53 exon 6 mutations were predicted by the country of
      residence of the patients. Our study identifies that there are differences in the
      types of mutations found in tumors from pancreatic carcinoma patients in Egypt
      and the US, and suggests that environmental factors may explain these
      differences.

PMID- 16619253
TI  - A comparison of bone formation in biphasic calcium phosphate (BCP) and
      hydroxyapatite (HA) implanted in muscle and bone of dogs at different time
      periods.
AB  - Physicochemical modification could implement synthetic materials into
      osteoinductive materials, which induce bone formation in nonosseous tissues. We
      hereby studied the relevance between the osteogenic capacities of osteoinductive
      materials in nonosseous tissues and in osseous sites. Biphasic calcium phosphate
      ceramic (BCP) and hydroxyapatite ceramic (HA) were implanted in femoral muscles
      and femoral cortical bone of dogs for 7, 14, 21, 30, 45, 60, 90, 180, and 360
      days, respectively. Two dogs were used in each time point. In each dog, four
      cylinders (phi5x6 mm) per material were implanted in femoral muscles and 2
      cylinders (phi5x6 mm) per material in femoral cortical bone. The harvested
      samples were processed for both histological and histomorphometric analyses. Bone
      was observed in BCP implanted in femoral muscles since day 30, while in HA since
      day 45. Quantitatively, more bone was formed in BCP than in HA at each time point
      after day 30 (p<0.05). The earlier and more bone formed in BCP than in HA
      suggests BCP a higher osteoinductive potential than HA in muscle. In femoral
      cortical bone defects, a bridge of bone in the defect with BCP was observed at
      day 21, while with HA at day 30. At days 14, 21, and 30, significantly more bone
      was formed in BCP than in HA (p<0.05). The results herein show that osteogenic
      capacities of osteoinductive materials in nonosseous tissues and osseous sites
      are correlated: the higher the osteoinductive potential of the material, the
      faster the bone repair.

PMID- 16619254
TI  - Branched peptide-amphiphiles as self-assembling coatings for tissue engineering
      scaffolds.
AB  - An important challenge in regenerative medicine is the design of suitable
      bioactive scaffold materials that can act as artificial extracellular matrices.
      We reported previously on a family of peptide-amphiphile (PA) molecules that self
      assemble into high-aspect ratio nanofibers under physiological conditions, and
      can display bioactive peptide epitopes along each nanofiber's periphery. One type
      of PA displays its epitope at a branched site using a lysine dendron, a molecular
      feature that improves epitope availability on the nanofiber surface. In this
      work, we describe the application of these branched PA (b-PA) systems as self
      assembling coatings for fiber-bonded poly(glycolic acid) scaffolds. b-PAs bearing
      variations of the RGDS adhesion epitope from fibronectin were shown by elemental
      analysis to coat repeatably onto fiber scaffolds. The retention of supramolecular
      organization after coating on the scaffold was demonstrated through spectroscopic
      identification of beta-sheet structures and the close association of hydrophobic
      tails in a model pyrene-containing PA system. Primary human bladder smooth muscle
      cells demonstrated greater initial adhesion to b-PA-functionalized scaffolds than
      to bare scaffolds or to those coated with linear PAs. This strategy of molecular
      design and coating may have potential application in bladder tissue regeneration.

PMID- 16619255
TI  - Tannic acid-stabilized pericardium tissue: IR spectroscopy, atomic force
      microscopy, and dielectric spectroscopy investigations.
AB  - Infrared (IR) spectroscopy, atomic force microscopy (AFM), and dielectric
      spectroscopy methods were employed to study structural and dynamic changes in the
      tannic acid (TA)-stabilized pericardium tissue. Chemically stabilized pericardium
      tissue is widely used in construction of the tissue derived bioprostheses. IR
      spectra recorded in the range 400-4000 cm-1 allowed us to recognize different
      types of TA-collagen interactions. Formation of hydrogen bonds between amine as
      well as amide NH groups from collagen and hydroxyl groups of TA was analyzed. The
      AFM imaging showed that the stabilization procedure with TA introduces
      considerable changes in both surface topography and thickness of collagen fibrils
      as well as in fibril arrangement on the tissue surface. It was found, that these
      structural changes have an impact on the dielectric behavior of the TA-stabilized
      tissue. The dielectric spectra for the native and TA-stabilized tissues were
      measured in the frequency and temperature ranges of 10(-1) -10(7) Hz and 120-270
      K, respectively. The dielectric spectra revealed the relaxation process due to
      orientation of bound water supplemented by the fluctuation of collagen polar side
      groups. At the temperatures above approximately 210 K, the relaxation due to ion
      migration process was observed. It was found that both relaxation processes were
      influenced by the TA-collagen interaction.

PMID- 16619256
TI  - Non-genomic immunosuppressive actions of progesterone inhibits PHA-induced
      alkalinization and activation in T cells.
AB  - Progesterone is an endogenous immunomodulator, and can suppress T-cell activation
      during pregnancy. When analyzed under a genome time scale, the classic steroid
      receptor pathway does not have any effect on ion fluxes. Therefore, the aim of
      this study was to investigate whether the non-genomic effects on ion fluxes by
      progesterone could immunosuppress phytohemagglutinin (PHA)-induced human
      peripheral T-cell activation. The new findings indicated that, first, only
      progesterone stimulated both [Ca2+]i elevation and pHi decrease; in contrast,
      estradiol or testosterone stimulated [Ca2+]i elevation and hydrocortisone or
      dexamethasone stimulated pHi decrease. Secondly, the [Ca2+]i increase by
      progesterone was dependent on Ca2+ influx, and the acidification was blocked by
      Na+/H+ exchange (NHE) inhibitor, 3-methylsulphonyl-4-piperidinobenzoyl, guanidine
      hydrochloride (HOE-694) but not by 5-(N,N-dimethyl)-amiloride (DMA). Thirdly,
      progesterone blocked phorbol 12-myristate 13-acetate (PMA) or PHA-induced
      alkalinization, but PHA did not prevent progesterone-induced acidification.
      Fourthly, progesterone did not induce T-cell proliferation; however, co
      stimulation progesterone with PHA was able to suppress PHA-induced IL-2 or IL-4
      secretion and proliferation. When progesterone was applied 72 h after PHA
      stimulation, progesterone could suppress PHA-induced T-cell proliferation.
      Finally, immobilization of progesterone by conjugation to a large carrier
      molecule (BSA) also stimulated a rapid [Ca2+]i elevation, pHi decrease, and
      suppressed PHA-induced proliferation. These results suggested that the non
      genomic effects of progesterone, especially acidification, are exerted via plasma
      membrane sites and suppress the genomic responses to PHA. Progesterone might act
      directly through membrane specific nonclassical steroid receptors to cause
      immunomodulation and suppression of T-cell activation during pregnancy.

PMID- 16619257
TI  - Mesenchymal stem cells as trophic mediators.
AB  - Adult marrow-derived Mesenchymal Stem Cells (MSCs) are capable of dividing and
      their progeny are further capable of differentiating into one of several
      mesenchymal phenotypes such as osteoblasts, chondrocytes, myocytes, marrow
      stromal cells, tendon-ligament fibroblasts, and adipocytes. In addition, these
      MSCs secrete a variety of cytokines and growth factors that have both paracrine
      and autocrine activities. These secreted bioactive factors suppress the local
      immune system, inhibit fibrosis (scar formation) and apoptosis, enhance
      angiogenesis, and stimulate mitosis and differentiation of tissue-intrinsic
      reparative or stem cells. These effects, which are referred to as trophic
      effects, are distinct from the direct differentiation of MSCs into repair tissue.
      Several studies which tested the use of MSCs in models of infarct (injured
      heart), stroke (brain), or meniscus regeneration models are reviewed within the
      context of MSC-mediated trophic effects in tissue repair.

PMID- 16619258
TI  - Molecular dynamics simulation and automated docking of the pro-apoptotic Bax
      protein and its complex with a peptide designed from the Bax-binding domain of
      anti-apoptotic Ku70.
AB  - Bax, a multi-domain protein belonging to the large family of Bcl-2 proteins, has
      a pivotal role for the initiation of the cytochrome c-mediated apoptosis, a vital
      physiologic process to eliminate damaged or unwanted cells. In response to
      specific stimuli Bax translocates from cytosol to mitochondria outer membrane
      where a process of oligomerization occurs with pore formation through which
      cytochrome c and other death molecules escape. The pro-death action of Bax is
      regulated by the interaction with other pro-survival proteins. However, the
      conformational changes and the structural details necessary for homo and hetero
      interaction with other regulating proteins are largely unknown. This article
      reports a combined investigation of molecular dynamics (MD) simulation and
      automated docking that evidence the molecular regions of Bax involved in the
      binding with anti-apoptotic exapeptide (Bip) designed from Ku70, a subunit of the
      protein complex essential for non-homologous DNA repair but that inhibits also
      the Bax translocation to mitochondria. Since Bip suppresses apoptosis induced by
      several anti-cancer drugs, it appears relevant to achieve a better understanding
      of the structural and dynamical aspects that characterize the Bip-Bax complex in
      view of potential therapeutic implications. The present results show that the Bax
      region with the highest affinity for Bip is located in proximity of BH3 homology
      domain of Bax and also involves the alpha-helices 1 and 8. Moreover, the
      comparison of essential motions of Bax at 300 and 400 K before and after the
      formation of the complex with Bip evidences how the binding with the exa-peptide
      affects the collective motions of specific molecular districts of Bax considered
      to have functional relevance.

PMID- 16619259
TI  - Chronic hyperglycemia modulates osteoblast gene expression through osmotic and
      non-osmotic pathways.
AB  - Insulin dependent diabetes mellitus (IDDM; type I) is a chronic disease stemming
      from little or no insulin production and elevated blood glucose levels. IDDM is
      associated with osteoporosis and increased fracture rates. The mechanisms
      underlying IDDM associated bone loss are not known. Previously we demonstrated
      that osteoblasts exhibit a response to acute (1 and 24 h) hyperglycemia and
      hyperosmolality. Here we examined the influence of chronic hyperglycemia (30 mM)
      and its associated hyperosmolality on osteoblast phenotype. Our findings
      demonstrate that osteoblasts respond to chronic hyperglycemia through modulated
      gene expression. Specifically, chronic hyperglycemia increases alkaline
      phosphatase activity and expression and decreases osteocalcin, MMP-13, VEGF and
      GAPDH expression. Of these genes, only MMP-13 mRNA levels exhibit a similar
      suppression in response to hyperosmotic conditions (mannitol treatment). Acute
      hyperglycemia for a 48-h period was also capable of inducing alkaline phosphatase
      and suppressing osteocalcin, MMP-13, VEGF, and GAPDH expression in differentiated
      osteoblasts. This suggests that acute responses in differentiated cells are
      maintained chronically. In addition, hyperglycemic and hyperosmotic conditions
      increased PPARgamma2 expression, although this increase reached significance only
      in 21 days chronic glucose treated cultures. Given that osteocalcin is suppressed
      and PPARgamma2 expression is increased in type I diabetic mouse model bones,
      these findings suggest that diabetes-associated hyperglycemia may modulate
      osteoblast gene expression, function and bone formation and thereby contribute to
      type I diabetic bone loss.

PMID- 16619260
TI  - Cloning and molecular dissection of the 8.8 kb pig uroplakin II promoter using
      transgenic mice and RT4 cells.
AB  - Uroplakin II (UPII) gene expression is highly tissue and cell specific, with mRNA
      present in the suprabasal cell layers of the bladder and urethra. Previous
      reports described the mouse UPII (mUPII) promoter as primarily urothelium
      selective. However, ectopic expression of a transgene under the 3.6 kb mUPII
      promoter was also detected in brain, kidney, and testis in some transgenic mouse
      lines. Here, we have cloned an 8.8 kb pig UPII (pUPII) promoter region and
      investigated which cells within the bladder and urethra express a transgene
      consisting of the pUPII promoter fused to human erythropoietin (hEPO) or a
      luciferase gene. pUPII-luciferase expression vectors with various deletions of
      the promoter region were introduced into mouse fibroblast (NIH3T3), Chinese
      hamster ovary (CHO), and human bladder transitional carcinoma (RT4). A 2.1 kb
      pUPII promoter fragment displayed high levels of luciferase activity in
      transiently transfected RT4 cells, whereas the 8.8 kb pUPII promoter region
      displayed only low levels of activity. The pUPII-hEPO expression vector was
      injected into the pronucleus of zygotes to make transgenic mice. To elucidate the
      in vivo molecular mechanisms controlling the tissue- and cell-specific expression
      of the pUPII promoter gene, transgenic mice containing 2.1 and 8.8 kb pUPII
      promoter fragments linked to the genomic hEPO gene were generated. An
      erythropoietin (EPO) assay showed that all nine transgenic lines carrying the 8.8
      kb construct expressed recombinant human erythropoietin (rhEPO) only in their
      urethra and bladder, whereas two transgenic lines carrying the 2.1 kb pUPII
      promoter displayed hEPO expression in several organs including bladder, kidney,
      spleen, heart, and brain. These studies demonstrate that the 2.1 kb promoter
      contains the DNA elements necessary for high levels of expression, but lacks
      critical sequences necessary for tissue-specific expression. We compared binding
      sites in the 2.1 and 8.8 kb promoter sequences and found five peroxisome
      proliferator responsive elements (PPREs) in the 8.8 kb promoter. Our data
      demonstrated that proliferator-activated receptor (PPAR)-gamma activator
      treatment in RT4 cells induced the elevated expression of hEPO mRNA under the
      control of the 8.8 kb pUPII promoter, but not the 2.1 kb promoter. Collectively,
      our data suggested that all the major trans-regulatory elements required for
      bladder- and urethra-specific transcription are located in the 8.8 kb upstream
      region and that it may enhance tissue-specific protein production and be of
      interest to clinicians who are searching for therapeutic modalities with high
      efficacy and low toxicity.

PMID- 16619262
TI  - Roles of COX-2 and iNOS in the bony repair of the injured growth plate cartilage.
AB  - Growth plate injuries often lead to bone growth defects, which primarily occur
      due to bony repair at injury sites. Bony repair is preceded by an injury-induced
      inflammatory response, which could play a role in regulating the repair process.
      Here, roles of two inflammatory mediators, cyclo-oxygenase 2 (COX-2) and
      inducible nitric oxide synthase (iNOS), in the injury responses were analysed by
      examining their gene expression and effects of blocking their activities,
      respectively, with celecoxib and aminoguanidine during 2 days prior to and until
      7 days after injury in a rat tibial growth plate injury model. Quantitative RT
      PCR assays revealed upregulated expression of COX-2 on days 1 and 4 and iNOS on
      day 1. Histological analysis of injury sites revealed significant reductions in
      inflammatory infiltrate (particularly neutrophils) on day 1 in treated groups
      compared to saline control. While bony tissue proportions at injury sites were
      unaffected by either treatment, mesenchymal tissue proportions were larger but
      cartilaginous tissue proportions were smaller on day 8 (though statistically
      insignificant), and bone remodelling appeared delayed with a smaller bone marrow
      proportion on day 14 in both treatment groups. These findings suggest that COX-2
      and iNOS mediate injury-induced inflammatory response, and may play a role in
      enhancing mesenchymal cell differentiation to cartilaginous cells and in
      promoting bone remodelling during bony repair of growth plate injury sites.
      Furthermore, increased expression of cartilage-related (collagen-2, collagen-10,
      SOX-9) and bone-related molecules (osteocalcin, cbfalpha-1) suggest involvement
      of both endochondral and direct bone formation mechanisms during bony repair.

PMID- 16619263
TI  - Regulatory processes affecting androgen receptor expression, stability, and
      function: potential targets to treat hormone-refractory prostate cancer.
AB  - Prostate cancer cells rely on androgen receptor (AR) for proliferation and
      survival. Therefore, curing prostate cancer will require elimination of AR.
      Although androgen is the natural ligand that activates AR, AR activity is also
      subject to regulation by growth factor/growth factor receptor-stimulated
      signaling pathways that control the cell cycle. Cell cycle regulatory proteins
      and protein kinases in signaling pathways affected by growth factors can lead to
      AR activation in the absence of androgen. While downstream signaling proteins
      such as cyclins, cyclin-dependent kinases (CDKs), and pRB can modulate AR
      activity, upstream signaling pathways involving protein kinases such as mitogen
      activated protein kinases, protein kinase A, and protein kinase B/Akt can affect
      post-translational modification of AR to affect not only AR function but also AR
      stability. Calcium and calmodulin (CaM), essential for proliferation and
      viability of a number of cells, including prostate cancer cells, play an
      important role in AR expression, stability, and function. CaM affects AR partly
      by interacting directly with AR and partly by activating protein kinases such as
      Akt and DNA-PK that can phosphorylate AR. The ubiquitin/26S proteasome pathway
      responsible for timely destruction of cell cycle regulatory proteins whose levels
      impede cell cycle progression also induces AR expression by activating NF-kappaB,
      and promotes AR activity by participating in the assembly of an AR transcription
      complex. Maspin, a serine protease inhibitor that is known mostly for its role as
      a tumor suppressor can also regulate AR intracellular localization and function
      by competing with AR for binding to the chaperone protein Hsp90 and co-repressor
      HDAC1, respectively. This perspective reviews the experimental evidence
      implicating these diverse cellular processes in AR expression, stability, and/or
      function, and presents a rationale for disrupting these cellular processes as a
      viable option for the treatment of both the hormone-sensitive and the hormone
      insensitive prostate cancer.

PMID- 16619264
TI  - Androgen receptor action in hormone-dependent and recurrent prostate cancer.
AB  - The importance of androgens and androgen receptors (AR) in primary prostate
      cancer is well established. Metastatic disease is usually treated with some form
      of androgen ablation, which is effective for a limited amount of time. The role
      of AR in prostate cancers that recur despite androgen ablation therapy is less
      certain. Most of these tumors express prostate specific antigen (PSA), an
      androgen-regulated gene; moreover, AR is generally highly expressed in recurrent
      prostate cancer. We propose that AR continues to play a role in many of these
      tumors and that it is not only the levels of AR, ligands, and co-regulators, but
      also the changes in cell signaling that induce AR action in recurrent prostate
      cancer. These pathways are, therefore, potential therapeutic targets.

PMID- 16619265
TI  - Regulation of dHAND protein expression by all-trans retinoic acid through ET
      1/ETAR signaling in H9c2 cells.
AB  - dHAND is thought to be a cardiac-restricted transcription factor during embryonic
      development. Vertebrate heart development involves many transcription factors
      such as Nkx2.5, GATA, and tbx5. All-trans retinoic acid (AtRA), the oxidative
      metabolite of vitamin A, can regulate the expression of these factors to affect
      embryonic heart development. However, the action of atRA on the expression of
      dHAND is rarely reported. To clarify whether atRA regulate the dHAND expression,
      we exposed cultured H9c2 cells (rat embryonic cardiomyocytes) to atRA and
      detected the protein expression of dHAND by Western blot analysis. We observed
      atRA can regulate the dHAND expression in a dose- and time-dependent manner. AtRA
      also inhibited endothelin-1 (ET-1) expression in a time-dependent manner. Further
      studies revealed that pretreatment with 10 microM BQ-123, a selective endothelin
      1 receptor (ETAR) antagonist, for 2 h can significantly counteract the inhibition
      of 5 microM atRA treatment for 2 h of dHAND mRNA and protein expression. Taken
      together, these results suggest that atRA regulates dHAND expression by ET-1/ETAR
      signal transduction pathway in H9c2 cells. The mechanism of ET-1/ETAR signaling
      in controlling the level of dHAND protein is to reduce the levels of dHAND mRNA.
      It is possible for atRA to exert its cardiac teratogenesis during vertebrate
      embryonic development in this way.

PMID- 16619266
TI  - Endodermal differentiation of murine embryonic carcinoma cells by retinoic acid
      requires JLP, a JNK-scaffolding protein.
AB  - Retinoic acid (RA) is a morphogen that induces endodermal differentiation of
      murine P19 embryonic carcinoma cells. RA-induced differentiation of P19 cells has
      been used as a model system to define the differentiation programs of pluripotent
      stem cells. Using this system it has been shown that G alpha13--the alpha-subunit
      of the heterotrimeric G protein G13--and its activation of JNK-module are
      critically required for the endodermal differentiation of P19 cells. However, the
      mechanism through which G alpha13 is linked to JNK-module is unknown. Here, we
      report that RA stimulates the expression of JNK-interacting leucine zipper
      protein (JLP), a newly identified JNK-scaffolding protein and its critical role
      in RA-mediated endodermal differentiation. Our results indicate that there is a
      physical association between JLP and G alpha13 in RA-stimulated P19 cells. More
      interestingly, silencing JLP abrogates RA-mediated endodermal differentiation of
      P19 cells analogous to the effects seen with the silencing of G alpha13 or JNK.
      Therefore, our studies presented here identify for the first time, a novel role
      for a newly identified scaffolding protein in RA-mediated endodermal
      differentiation, providing a new signaling conduit to transmit signals from RA to
      JNK module.

PMID- 16619267
TI  - Reduction of anabolic signals and alteration of osteoblast nuclear morphology in
      microgravity.
AB  - Bone loss has been repeatedly documented in astronauts after flight, yet little
      is known about the mechanism of bone loss in space flight. Osteoblasts were
      activated during space flight in microgravity (microg) with and without a 1
      gravity (1 g) field and 24 genes were analyzed for early induction. Induction of
      proliferating cell nuclear antigen (PCNA), transforming growth factor beta
      (TGFbeta), cyclo-oxygenase-2 (cox-2), cpla2, osteocalcin (OC), c-myc, fibroblast
      growth factor-2 (fgf-2), bcl2, bax, and fgf-2 message as well as FGF-2 protein
      were significantly depressed in microg when compared to ground (gr). Artificial
      onboard gravity normalized the induction of c-myc, cox-2, TGFbeta, bax, bcl2, and
      fgf-2 message as well as FGF-2 protein synthesis in spaceflight samples. In
      normal gravity, FGF-2 induces bcl2 expression; we found that bcl2 expression was
      significantly reduced in microgravity conditions. Since nuclear shape is known to
      elongate in the absence of mitogens like FGF-2, we used high-resolution image
      based morphometry to characterize changes in osteoblast nuclear architecture
      under microgravity, 1 g flight, and ground conditions. Besides changes in cell
      shape (roundish/elliptic), other high-resolution analyses show clear influences
      of gravity on the inner nuclear structure. These changes occur in the texture,
      arrangement, and contrast of nuclear particles and mathematical modeling defines
      the single cell classification of the osteoblasts. Changes in nuclear structure
      were evident as early as 24 h after exposure to microgravity. This documented
      alteration in nuclear architecture may be a direct result of decreased expression
      of autocrine and cell cycle genes, suggesting an inhibition of anabolic response
      in microg. Life on this planet has evolved in a normal gravity field and these
      data suggest that gravity plays a significant role in regulation of osteoblast
      transcription.

PMID- 16619268
TI  - Serum and glucocorticoid-regulated protein kinases: variations on a theme.
AB  - The phosphatidylinositol 3' kinase (PI3K)-signaling pathway plays a critical role
      in a variety of cellular responses such as modulation of cell survival, glucose
      homeostasis, cell division, and cell growth. PI3K generates important lipid
      second messengers-phosphatidylinositides that are phosphorylated at the 3'
      position of their inositol ring head-group. These membrane restricted lipids act
      by binding with high affinity to specific protein domains such as the pleckstrin
      homology (PH) domain. Effectors of PI3K include molecules that harbor such
      domains such as phosphoinositide-dependent kinase (PDK1) and protein kinase B
      (PKB), also termed Akt. The mammalian genome encodes three different PKB genes
      (alpha, beta, and gamma; Akt1, 2, and 3, respectively) and each is an attractive
      target for therapeutic intervention in diseases such as glioblastoma and breast
      cancer. A second family of three protein kinases, termed serum and glucocorticoid
      regulated protein kinases (SGKs), is structurally related to the PKB family
      including regulation by PI3K but lack a PH domain. However, in addition to PH
      domains, a second class of 3' phosphorylated inositol phospholipid-binding
      domains exists that is termed Phox homology (PX) domain: this domain is found in
      one of the SGKs (SGK3). Here, we summarize knowledge of the three SGK isoforms
      and compare and contrast them to PKB with respect to their possible importance in
      cellular regulation and potential as therapeutic targets.

PMID- 16619269
TI  - 2-methoxyestradiol inhibits differentiation and is cytotoxic to osteoclasts.
AB  - 2-Methoxyestradiol (2-ME), a naturally occurring metabolite of 17beta-estradiol,
      is highly cytotoxic to a wide range of tumor cells but is harmless to most normal
      cells. However, 2-ME prevented bone loss in ovariectomized rats, suggesting it
      inhibits bone resorption. These studies were performed to determine the direct
      effects of 2-ME on cultured osteoclasts. 2-ME (2 microM) reduced osteoclast
      number by more than 95% and induced apoptosis in three cultured osteoclast model
      systems (RAW 264.7 cells cultured with RANKL, marrow cells co-cultured with
      stromal support cells, and spleen cells cultured without support cells in media
      supplemented with RANKL and macrophage colony stimulating factor (M-CSF)). The 2
      ME-mediated effect was ligand specific; 2-hydroxyestradiol (2-OHE), the immediate
      precursor to 2-ME, exhibited less cytotoxicity; and 2-methoxyestrone (2-MEOE1)
      the estrone analog of 2-ME, was not cytotoxic. Co-treatment with ICI 182,780 did
      not antagonize 2-ME, suggesting that the cytotoxicity was not estrogen receptor
      dependent. 2-ME-induced cell death in RAW 264.7 cells coincided with an increase
      in gene expression of cytokines implicated in inhibition of differentiation and
      induction of apoptosis. In addition, the 2-ME-mediated decrease in cell survival
      was partially inhibited by anti-lymphotoxin(LT)beta antibodies, suggesting that 2
      ME-dependent effects involve LTbeta. These results suggest that 2-ME could be
      useful for treating skeletal diseases in which bone resorption is increased, such
      as postmenopausal osteoporosis and cancer metastasis to bone.

PMID- 16619270
TI  - Rapid detection of submicroscopic chromosomal rearrangements in children with
      multiple congenital anomalies using high density oligonucleotide arrays.
AB  - Chromosomal rearrangements such as microdeletions and interstitial duplications
      are the underlying cause of many human genetic disorders. These disorders can
      manifest in the form of multiple congenital anomalies (MCA), which are a
      significant cause of morbidity and mortality in children. The major limitations
      of cytogenetic tests currently used for the detection of such chromosomal
      rearrangements are low resolution and limited coverage of the genome. Thus, it is
      likely that children with MCA may have submicroscopic chromosomal rearrangements
      that are not detectable by current techniques. We report the use of a
      commercially available, oligonucleotide-based microarray for genome-wide analysis
      of copy number alterations. First, we validated the microarray in patients with
      known chromosomal rearrangements. Next, we identified previously undetected, de
      novo chromosomal deletions in patients with MCA who have had a normal high
      resolution karyotype and subtelomeric fluorescence in situ hybridization (FISH)
      analysis. These findings indicate that high-density, oligonucleotide-based
      microarrays can be successfully used as tools for the detection of chromosomal
      rearrangement in clinical samples. Their higher resolution and commercial
      availability make this type of microarray highly desirable for application in the
      diagnosis of patients with multiple congenital defects.

PMID- 16619272
TI  - T-cell cytokine induction of BMP-2 regulates human mesenchymal stromal cell
      differentiation and mineralization.
AB  - How T-cells, attracted to local sites of inflammation in arthritides, affect
      heterotopic ossification is presently unknown. Here, we tested the hypothesis
      that T-cell cytokines play a role in the differentiation of human mesenchymal
      stromal cells (HMSC) into the osteoblast phenotype by inducing autologous BMP-2,
      providing a possible mechanism for heterotopic ossification. HMSC from multiple
      donor bones were treated with either activated T-cell conditioned medium (ACTTCM)
      or physiological concentrations of the major inflammatory cytokines, TNF-alpha,
      TGF-beta, IFN-gamma, and IL-17 (TTII), individually or in combinations. ACTTCM
      induced BMP-2 protein in a time-dependent manner over a 48 h period and alkaline
      phosphatase (AlkP) within 7 days. In combination, TTII, like ACTTCM, induced AlkP
      and synergistically induced BMP-2 protein. Either individually, or in
      combinations of up to three, the T-cell cytokines failed to induce BMP-2 above
      control levels while a combination of all four cytokines synergistically induced
      BMP-2 10-fold as assessed by ELISA. TTII induced mineralized matrix as
      effectively as dexamethasone. Inhibition of p38 MAPK completely inhibited TTII
      induced BMP-2 production and matrix mineralization. Real time RT-PCR analysis
      demonstrated a striking early (within 4 h) increase in BMP-2 gene expression by
      TTII, which was suppressed by p38 MAP kinase inhibition. In localized chronic
      inflammatory diseases, T-cell cytokines released at localized sites of
      inflammation may be the driving force for differentiation of local mesenchymal
      stromal cells into the osteoblast phenotype thereby playing a significant role in
      the heterotopic ossification observed in these diseases.

PMID- 16619271
TI  - Role of metal-responsive transcription factor-1 (MTF-1) in EGF-dependent DNA
      synthesis in primary hepatocytes.
AB  - Metal-responsive transcription factor-1 (MTF-1), which is involved in sensing
      heavy metal load, induces the transcription of several protective genes. The
      mouse Mtf-1 gene is essential, and Mtf-1(-/-) embryos die from liver
      degeneration. We showed that DNA synthesis induced in hepatocytes by epidermal
      growth factor (EGF) was delayed by inhibition of MTF-1. To inhibit MTF-1
      activity, MTFDeltaC, a C-terminal deletion mutant of MTF-1, was expressed by
      infection with the virus Ad5MTFDeltaC. Lactate dehydrogenase (LDH) release and/or
      caspase-3/7 activation was not observed under our experimental conditions. The
      inhibitory effect of MTFDeltaC on EGF-dependent DNA synthesis in hepatocytes was
      not eliminated by zinc addition. EGF-dependent extracellular signal-related
      kinase (ERK) phosphorylation, an essential reaction for EGF-dependent DNA
      synthesis, was decreased in MTF-1-inhibited hepatocytes. Moreover, decrease of
      ERK phosphorylation was observed by using siRNA in MTF-1-downregulated
      hepatocytes. These results indicate that MTF-1 is particularly important for
      proper hepatocyte proliferation. This is the first report to suggest the function
      of MTF-1 in the ERK pathway.

PMID- 16619273
TI  - Repression of transcription by TSGA/Jmjd1a, a novel interaction partner of the
      ETS protein ER71.
AB  - Testis-specific gene A (TSGA) was originally identified in rat and shown to be
      expressed within the testes. Here, we have cloned the murine homolog [also known
      as jumonji domain-containing 1a (Jmjd1a)] and for the first time characterized
      the TSGA protein and its functions. Although murine TSGA is expressed in testes,
      its mRNA is also present in many other tissues, including heart, thymus, liver,
      and skin. Immunostaining revealed that TSGA is a nuclear protein, whose N
      terminus contains a putative nuclear localization signal. TSGA displays
      significant homology to a suspected tumor suppressor and coactivator (5qNCA), to
      a thyroid hormone receptor interacting protein (TRIP8) and to the corepressor
      Hairless, pointing at a role of TSGA in transcription regulation. Indeed, TSGA
      contains several functional transcription repression domains. In addition, TSGA
      interacts both in vitro and in vivo with ER71 (ETS related 71), a transcription
      factor that is expressed in the testes of adult mice and during embryogenesis.
      Specifically, the N-terminus of TSGA and the C-terminus of ER71 are primarily
      engaged in their complex formation. Furthermore, TSGA impairs the ability of ER71
      to activate transcription from the matrix metalloproteinase-1 promoter. Thus,
      TSGA may modulate the function of ER71 and thereby affect spermatogenesis as well
      as embryonic development.

PMID- 16619274
TI  - PET-CT vs contrast-enhanced CT: what is the role for each after chemoradiation
      for advanced oropharyngeal cancer?
AB  - PURPOSE: The aim of our study was to assess the utility of positron emission
      tomography (PET) and 2 fluoro-2-deoxy-D-glucose coupled with neck CT compared
      with contrast-enhanced CT in predicting persistent cancer either at the primary
      site or cervical lymphatics in patients with oropharyngeal cancer treated with
      concurrent chemoradiation METHODS: Thirty consecutive patients underwent clinical
      examination, PET-CT, and contrast-enhanced CT to assess response after the
      completion of the treatment. The outcome variable was positive tissue diagnosis
      or negative disease at 6 months. Sensitivity, specificity, positive predictive
      value (PPV), negative predictive value (NPV), and accuracy were calculated for
      the primary site as well as cervical disease. RESULTS: Contrast-enhanced CT alone
      showed the best accuracy in detecting disease at the primary site after treatment
      (85.7%). Accuracy in evaluating residual tumor in the cervical lymphatics for
      contrast-enhanced CT and PET-CT was 59.3% and 74.1%, respectively. For evaluating
      the neck, PET-CT and contrast-enhanced CT demonstrated 100% NPV, but the PPV was
      36.3% and 26.6%, respectively. CONCLUSIONS: In this preliminary study, PET-CT
      seems to be superior to contrast-enhanced CT in predicting persistent disease in
      the neck after chemoradiation for oropharyngeal or unknown primary cancer, but
      not at the primary site. However, the possibility of a false-positive result in
      the neck remains high, and thus overtreatment may result. Even more concerning
      are the false-negative results. Larger, prospective studies will be important in
      defining the role of PET-CT in obviating the need for salvage neck dissections
      after chemoradiation.

PMID- 16619275
TI  - Taste dysfunction in patients receiving radiotherapy.
AB  - BACKGROUND: Taste loss is a major cause of morbidity in patients undergoing head
      and neck irradiation. METHODS: In a prospective study, 51 patients undergoing
      radical head and neck irradiation at the Tokyo University Hospital were assessed
      for taste loss. Taste ability was measured by the taste threshold for the four
      basic tastes (sweet, sour, salt, and bitter qualities) plus another taste of
      "umami" quality using a filter-paper-disc method in patients before, during, and
      after radiotherapy (RT). RESULTS: All tastes declined on the fifth week after the
      start of RT and improved on the 11th week. Anatomic pathologic analyses in rats
      revealed that taste buds diminished completely on the sixth day after irradiation
      of 15 Gy in a single fraction, and the appearance of taste buds returned almost
      to the preirradiation state on the 28th day. CONCLUSIONS: The main cause of taste
      disorder resulting from RT was believed to be a disappearance of taste buds and
      not damage to the taste nerves.

PMID- 16619276
TI  - Predictive value of laminin-5 and membrane type 1-matrix metalloproteinase
      expression for cervical lymph node metastasis in T1 and T2 squamous cell
      carcinomas of the tongue and floor of the mouth.
AB  - BACKGROUND: Laminin-5 (Ln-5) cleaved by membrane type 1-matrix metalloproteinase
      (MT1-MMP) enhances the migration of tumor cells. The purpose of this study was to
      determine whether or not enhanced expression of both Ln-5 and MT1-MMP was
      associated with lymph node metastasis in patients with T1 and T2 squamous cell
      carcinoma (SCC) of the tongue and floor of the mouth. METHODS: By use of biopsy
      specimens of primary tumors from 57 patients, intratumoral expression of Ln-5 and
      MT1-MMP was evaluated immunohistochemically and its association with node
      metastasis analyzed. RESULTS: The tumors were categorized into three groups: Ln-5
      focal type/MT1-MMP (-) (group I, n = 14), Ln-5 focal type/ MT1-MMP (+) and Ln-5
      diffuse type/MT1-MMP (-) (group II, n = 16), and Ln-5 diffuse type/MT1-MMP (+)
      (group III, n = 27). The incidence of node metastasis (initial and latent
      metastases) was two of 14 (14.3%), five of 16 (31.3%), and 15 of 27 (55.6%) in
      groups I, II, and III, respectively. Multivariate analysis identified tumor
      thickness (odds ratio, 4.751; p = .0152) and Ln-5/ MT1-MMP expression (odds
      ratio, 3.795, p = .0304) as independent factors of node metastasis. Moreover, in
      35 patients with N0 disease, Ln-5/MT1-MMP expression was the only parameter
      associated with latent node metastasis (odds ratio, 12.800, p = .0247).
      CONCLUSION: These results suggest that immunohistochemical evaluation of Ln-5 and
      MT1-MMP expression is useful for identifying patients with T1 and T2 SCC of the
      tongue and floor of the mouth who should be treated with elective neck
      dissection.

PMID- 16619277
TI  - Complete orbit and forehead reconstruction using a free latissimus dorsi flap and
      MEDPOR implants.
AB  - BACKGROUND: Reconstruction of enormous composite defects of the face in the
      presence of meningitis is a difficult problem. We present a case of a 29-year-old
      man with a huge, posttraumatic bone and soft tissue defect of the upper half of
      the left side of the face (orbit-zygoma-frontal-partial temporal bones), frontal
      lobe of the brain, and enucleated eye with intact facial skin. METHODS: An
      initial reconstruction using cement was complicated by multiple episodes of
      meningitis. In a multiple-stage procedure, we used a free latissimus dorsi muscle
      flap to re-construct the soft tissue defect and control the infection, a complete
      left orbit and frontal MEDPOR implant for the bone defect, and also an orbital
      sphere MEDPOR implant for the eyeball. RESULTS: In a 2-year follow-up, no
      infection was observed, and the cosmetic result is satisfactory. CONCLUSION: The
      combination of free flap and MEDPOR implants demonstrates an alternative method
      for reconstruction of complicated facial defects.

PMID- 16619278
TI  - Organ preservation for advanced laryngeal carcinoma.
AB  - BACKGROUND: Inclusion of patients with mobile vocal cords on larynx preservation
      trials may lead to overstatement of larynx preservation (LPR) and survival (OS)
      rates. METHODS: This is a retrospective review of patients at our institution who
      would have been eligible for the Department of Veterans Affairs Laryngeal Cancer
      Study Group (VA) and Radiation Therapy Oncology Group/Head and Neck Intergroup
      (RTOG 91-11) clinical trials. No laryngeal conservation procedure could be
      performed in patients with mobile vocal cords. RESULTS: One hundred one patients
      at our institution would have been eligible for the VA trial. The 2-year OS was
      76% for total laryngectomy and 90% for radiotherapy patients (p = .28) compared
      with 68% reported for the VA trial. Seventy-three patients at our institution
      would have been eligible for the RTOG 91-11 trial. The 5-year OS was 52% for
      total laryngectomy and 63% for radiotherapy patients (p = .18) compared with 55%
      reported for the RTOG 91-11 trial. Radiotherapy patients had an LPR of 80% (VA
      trial) and 86% (RTOG 91-11 trial). CONCLUSION: It is unlikely that inclusion of
      patients with mobile vocal cords had a significant impact on OS or LPR for the VA
      and RTOG 91-11 larynx preservation trials.

PMID- 16619279
TI  - Internal mammary artery perforator (IMAP) flap for tracheostoma reconstruction.
AB  - BACKGROUND: Tracheostoma reconstruction requires a thin flap to avoid occlusion.
      Although the deltopectoral flap has been used as a rotational flap for decades,
      clinical use of a true internal mammary artery perforator island flap has not
      been reported. METHODS: In two cases, tracheostoma and anterior neck
      reconstruction were performed by use of an internal mammary artery perforator
      flap as a pedicled island flap. One flap was based on the perforator vessels in
      the second intercostal space and, the other, on the third. Donor sites were
      closed primarily in both patients. RESULTS: The internal mammary artery
      perforator flaps were well perfused in both cases. Both flaps healed
      uneventfully, with reliable reconstruction of the tracheal stoma and coverage of
      the anterior neck, although overall prognoses were poor. CONCLUSION: The internal
      mammary artery perforator flap is a relatively thin and reliable flap for
      tracheostoma and lower neck reconstruction.

PMID- 16619280
TI  - Successful myoblast transplantation in rat tongue reconstruction.
AB  - BACKGROUND: Controversy exists regarding the success of myoblast transplantation.
      The purpose of this study was to determine the survival of transplanted myoblasts
      in a rat tongue reconstruction model by using fluorescently labeled myoblasts and
      surgical stains to mark the location of the pocket into which transplanted cells
      were delivered. We evaluated tongue histology after myoblast transplantation
      under the hypothesis that myoblast transplantation will promote muscle
      regeneration and result in minimal scar tissue formation. METHODS: Sterile
      solutions of 1:10 India ink, 1% methylene blue, and 1% crystal violet were
      applied to the inner lining of a left-sided mucosa-sparing hemiglossectomy
      pocket. After air-drying, the hemiglossectomy defect was filled with collagen gel
      and closed. The tongues were evaluated histologically at 6 weeks. Next, myoblasts
      were cultured and labeled with three commercially available fluorescent dyes, 5
      chloromethyl-fluorescein diacetate (CMFDA), chloromethylbenzamido (CM-DiI), and
      fluorescently labeled microspheres (FLMs), to determine which would optimally
      label myoblasts in a tongue reconstruction model. Next, Lewis rats underwent left
      hemiglossectomy, and the created pockets were coated with 1:10 India ink. Control
      animals received collagen gel alone, whereas experimental animals received
      labeled myoblast/collagen constructs into the tongue defect. Tongues were
      harvested at intervals to determine the presence of labeled fluorescent cells,
      the relative numbers of viable myoblasts, and the degree of scarring. RESULTS:
      India ink coating of the hemiglossectomy pocket caused minimal inflammation and
      lasted longer than the other tested dyes. CMFDA and FLMs both successfully label
      myoblasts for transplantation. In vivo, donor cells were observed in all
      specimens at week 0 with increasing numbers of cells and muscle formation,
      determined by desmin immunofluorescence, after 6 weeks. There was less scar
      tissue contracture in the experimental group and a significant increase in the
      amount of desmin-stained muscle in the surgical defect. CONCLUSIONS: India ink is
      an appropriate vehicle for intra-operative marking of a hemiglossectomy cavity.
      The introduction of myoblast/collagen constructs into the rat hemiglossectomy
      defect increases the amount of regenerated muscle, results in less scar
      contracture, and may increase meaningful tongue function.

PMID- 16619281
TI  - Potent inhibitory effects of resveratrol derivatives on progression of prostate
      cancer cells.
AB  - Resveratrol has been identified as a potent anticancer agent in a variety of
      studies. In this study, several resveratrol derivatives were synthesized and
      investigated in the search for an anticancer agent with higher efficacy than
      resveratrol. During our examination of cancer cell lines, compounds C, F, and G
      evidenced higher inhibitory activity than resveratrol with regard to the growth
      of PC-3 and LNCaP human prostate cancer cells. Moreover, four derivatives of
      resveratrol evidenced potent growth inhibitory activity (IC50 0.01-0.04 microM)
      in LNCaP cells. The levels of activity in these derivatives were 25-100 times
      stronger than that associated with resveratrol (IC50 1.0 microM). Our results
      suggested that compounds C, D, F, and G might function as anticancer agents on
      prostate tumors. This study also contains a discussion regarding the structure
      activity relationships of several resveratrol derivatives.

PMID- 16619282
TI  - Synthesis of substituted benzylamino- and heterocyclylmethylamino carbodithioate
      derivatives of 4-(3H)-quinazolinone and their cytotoxic activity.
AB  - A new series of substituted benzylamino- and heterocyclylmethylamino
      carbodithioate derivatives of 4-(3H)-quinazolinone were synthesized via four
      steps starting from 2-amino-5-methylbenzoic acid and initially screened against A
      549 (human non-small cell lung cancer), HCT-8 (human colon cancer), and Bel-7402
      (human liver cancer) cell lines at the single concentration of 5 microg/mL using
      the colorimetric MTT assay. The IC50 values were determined for the compounds
      reaching > or = 70% inhibition in primary screening by serial dilution. Among the
      newly synthesized compounds, 9n exhibited potent in vitro cytotoxicity against A
      549, HCT-8, and Bel-7402 cell lines with the IC50 values of 1.65, 0.93, and 1.43
      microM, respectively.

PMID- 16619283
TI  - Antileishmanial and antibacterial activity of a new pyrazole derivative
      designated 4-[2-(1-(ethylamino)-2-methyl- propyl)phenyl]-3-(4-methyphenyl)-1
      phenylpyrazole.
AB  - Here, we report for the first time the synthesis and the antileishmanial activity
      of a new pyrazole derivative, namely 4-[2-(1-(ethylamino)-2-methylpropyl)phenyl]
      3-(4-methyphenyl)-1-phenylpyrazole). Micromolar concentrations of this compound
      were found to inhibit the in vitro multiplication of Leishmania tropica,
      Leishmania major, and Leishmania infantum, three species causing different forms
      of leishmaniasis. Furthermore, the 50% inhibitory concentration (IC50) values for
      the compound are only slightly higher than those of amphotericin B, one of the
      most active antileishmanial agents used as a satisfactory substitute in cases not
      responding to pentostam. The IC50 values after 48 h for L. tropica, L. major, and
      L. infantum promastigote growth were 0.48 microg/mL, 0.63 microg/mL and 0.40
      microg/mL, respectively for the compound, while they were 0.23 microg/mL, 0.29
      microg/mL and 0.24 microg/mL, respectively for amphotericin B. We also tested
      this compound for its antibacterial activity against several bacteria. The
      strongest antibacterial activity was observed against Entrococcus feacalis and
      Staphylococcus aureus with a minimal inhibitory concentration (MIC) of 60
      microg/mL.

PMID- 16619284
TI  - Dimorphic Plasmodium falciparum merozoite surface protein-1 epitopes turn off
      memory T cells and interfere with T cell priming.
AB  - The leading blood-stage malaria vaccine candidate antigen, Plasmodium falciparum
      merozoite surface protein-1 (MSP-1) occurs in two major allelic types worldwide.
      The molecular basis promoting this stable dimorphism is unknown. In this study,
      we have shown that allelic altered peptide ligand (APL) T cell epitopes of MSP-1
      mutually inhibited IFN-gamma secretion as well as proliferation of CD4+ T cells
      in 27/34 malaria exposed Gambian volunteers. Besides this inhibition of malaria
      specific immunity, the same variant epitopes were also able to impair the priming
      of human T cells in malaria naive individuals. Epitope variants capable of
      interfering with T cell priming as well as inhibiting memory T cell effector
      functions offer a uniquely potent combination for immune evasion. Indeed,
      enhanced co-habitation of parasites bearing such antagonistic allelic epitope
      regions was observed in a study of 321 West African children, indicating a
      survival advantage for parasites able to engage this inhibitory immune
      interference mechanism.

PMID- 16619285
TI  - Interleukin-15 mediates protection against experimental tuberculosis: a role for
      NKG2D-dependent effector mechanisms of CD8+ T cells.
AB  - CD8+ T cells are involved in protection against Mycobacterium tuberculosis
      infection and represent a promising target for new vaccine strategies. Because IL
      15 is important for the homeostasis of CD8+ T cells, we studied the immune
      response in IL-15-deficient mice during tuberculosis. In the absence of IL-15,
      CD8+ T cells failed to efficiently accumulate in draining lymph nodes and at the
      site of infection. The expression of antigen-specific effector functions, such as
      the production of interferon-gamma and cytotoxicity, were impaired in CD8+ T
      cells, but not CD4+ T cells, from IL-15-deficient mice. This defect was
      associated with an increased mortality of IL-15-deficient mice during the chronic
      phase of infection. The lectin-like stimulatory receptor natural killer group 2D
      (NKG2D) was up-regulated on CD8+ T cells only from wild-type mice, but not from
      IL-15-deficient mice. Mechanistically, blocking NKG2D function with an mAb
      inhibited M. tuberculosis-directed CD8+ T cell responses in vitro. We conclude
      that in addition to regulating the expansion of CD8+ T cells, IL-15 is also
      necessary for inducing effector mechanisms in CD8+ T cells that depend on NKG2D
      expression. Hence, our results implicate IL-15 and NKG2D as promising targets for
      modulating CD8+ T cell-mediated protection against tuberculosis.

PMID- 16619286
TI  - DX5+ NKT cells induce the death of colitis-associated cells: involvement of
      programmed death ligand-1.
AB  - NKT cells are activated by CD1d and show an immune regulating function. Here, we
      investigated whether DX5+ NKT cells could be used to reduce colitis in a chronic
      colitis mouse model and studied the potential immunological mechanisms involved.
      Chronic colitis was induced either by transfer of enriched CD62L+ CD4+ T cells to
      severe-combined-immunodeficient mice or by feeding dextran sodium sulfate to
      immune competent mice. DX5+ NKT cells were transferred to mice with chronic
      colitis. Co-transfer of DX5+ NKT cells, but not CD8+ control cells, prevented the
      onset of colitis, and the immune regulatory effect of DX5+ NKT cells was
      completely abrogated by injecting CD1d blocking antibody. Moreover, DX5+ NKT
      cells reduced established colitis in both chronic colitis models. In vitro, DX5+
      NKT cells induced cell death of colon-infiltrating lymphocytes isolated from
      diseased mice. This effect was inhibited in the presence of either anti-CD1d or
      anti-programmed death ligand-1 (PD-L1) blocking antibodies. The specific potency
      of DX5+ NKT cells in regulating chronic colitis in two mouse models is
      demonstrated. In vitro testing suggests that DX5+ NKT cells activated by CD1d
      induce cell death of colitis-inducing lymphocytes, which is mediated through PD
      L1. Therefore, DX5+ NKT cells could be important in the regulation of immune
      responses associated with chronic colitis.

PMID- 16619287
TI  - Heat shock fusion protein induces both specific and nonspecific anti-tumor
      immunity.
AB  - Mucin 1 (MUC1) is a tumor antigen, and the most important epitopes that can
      induce cytotoxic T lymphocytes (CTL) reside in the variable-number tandem repeats
      (VNTR). Heat shock protein (HSP) complexes isolated from tumors have been shown
      to induce specific anti-tumor immunity. HSP alone can also induce nonspecific
      immunity. To explore the possibility to utilize the specific anti-tumor immunity
      induced by MUC1 VNTR and the nonspecific immunity induced by HSP, we constructed
      a recombinant protein (HSP65-MUC1) by fusing Bacillus Calmette-Guerin-derived
      HSP65 with the MUC1 VNTR peptide and tested its ability to induce anti-tumor
      activities in a tumor challenge model. The growth of MUC1-expressing tumors was
      significantly inhibited in mice immunized with HSP65-MUC1, both before and after
      tumor challenge. A much larger percentage of immunized mice survived the tumor
      challenge than non-immunized mice. Correlating with the anti-tumor activity,
      HSP65-MUC1 was shown to induce MUC1-specific CTL as well as nonspecific anti
      tumor immunity. In the human system, HSP65-MUC1-loaded human DC induced the
      generation of autologous MUC1-specific CTL in vitro. These results suggest that
      exogenously applied HSP65-MUC1 may be used to treat MUC1 tumors by inducing the
      epitope-specific CTL as well as nonspecific anti-tumor responses mediated by the
      HSP part of the fusion protein.

PMID- 16619288
TI  - Intranasal immunisation with inactivated RSV and bacterial adjuvants induces
      mucosal protection and abrogates eosinophilia upon challenge.
AB  - We have previously shown that following intranasal exposure to influenza virus,
      specific plasma cells are generated in the nasal-associated lymphoid tissue
      (NALT) and maintained for the life of the animal. However, we also showed that
      following infection with respiratory syncytial virus (RSV), specific plasma cells
      are generated in the NALT but wane quickly and are not maintained even after
      challenge, even though RSV-specific serum antibody responses remain robust. Only
      infection with influenza virus generated sterilising immunity, implying a role
      for these long-lived plasma cells in protection. We show here that the RSV
      specific IgA NALT plasma cell population and lung antibody levels can be
      substantially boosted, both at acute and memory time points, by intranasal
      immunisation with inactivated RSV (iRSV) in combination with bacterial outer
      membrane vesicles (OMV) compared to live RSV alone. Finally, challenge with live
      RSV showed that immunisation with iRSV and OMV protect against both virus
      replication in the lung and the eosinophil infiltrate generated by either live
      RSV or iRSV alone. These data show that immunisation with iRSV and OMV maintains
      a NALT RSV-specific plasma cell population and generates an efficient protective
      immune response following RSV infection.

PMID- 16619289
TI  - Roles for phosphoinositide 3-kinases, Bruton's tyrosine kinase, and Jun kinases
      in B lymphocyte chemotaxis and homing.
AB  - B lymphocyte chemokine receptors signal to downstream effectors by activating
      heterotrimeric G proteins. However, many of these effectors remain unknown and
      the known ones often have ill-defined roles in B cell trafficking. Here we report
      that pharmacological inhibitors of phosphoinositide 3-kinases (wortmannin, WMN),
      Bruton's tyrosine kinase (LFM-A13), and Jun kinases (SP600125) all significantly
      impair CXCL12-induced mouse B cell chemotaxis and that of a human B lymphoma cell
      line. Examination of two CXCR4-induced signaling pathways revealed that LFM-A13
      and WMN blocked Akt activation, while SP600125 and WMN blocked JNK activation.
      Each of the inhibitors impaired the homing of transferred B cells to peripheral
      lymph nodes. Intravital imaging of control and inhibitor-treated mouse B cells in
      the inguinal lymph node high endothelial venules (HEV) demonstrated a 17%, 35%,
      and 60% reduction in the number of firmly adherent B cells with LFM-A13,
      SP600125, and WMN, respectively. These results implicate chemokine receptor
      mediated activation of phosphoinositide 3-kinases in the firm adhesion of mouse B
      cells within peripheral lymph node HEV, while Bruton's tyrosine kinase and JNK
      activation are less important and more likely needed during B cell transmigration
      through the endothelium and/or trafficking into the lymph node parenchyma.

PMID- 16619290
TI  - IL-22 regulates the expression of genes responsible for antimicrobial defense,
      cellular differentiation, and mobility in keratinocytes: a potential role in
      psoriasis.
AB  - IL-22 is an IFN-IL-10 cytokine family member, which is produced by activated Th1
      and NK cells and acts primarily on epithelial cells. Here we demonstrate that IL
      22, in contrast to its relative IFN-gamma, regulates the expression of only a few
      genes in keratinocytes. This is due to varied signal transduction. Gene
      expressions regulated by IL-22 should enhance antimicrobial defense [psoriasin
      (S100A7), calgranulin A (S100A8), calgranulin B (S100A9)], inhibit cellular
      differentiation (e.g., profilaggrin, keratins 1 and 10, kallikrein 7), and
      increase cellular mobility [e.g., matrix metalloproteinease 1 (MMP1, collagenase
      1), MMP3 (stromelysin 1), desmocollin 1]. In contrast, IFN-gamma favored the
      expression of MHC pathway molecules, adhesion molecules, cytokines, chemokines,
      and their receptors. The IL-22 effects were transcriptional and either
      independent of protein synthesis and secretion, or mediated by a secreted
      protein. Inflammatory conditions, but not keratinocyte differentiation, amplified
      the IL-22 effects. IL-22 application in mice enhanced cutaneous S100A9 and MMP1
      expression. High IL-22 levels in psoriatic skin were associated with strongly up
      regulated cutaneous S100A7, S100A8, S100A9, and MMP1 expression. Psoriatic
      patients showed strongly elevated IL-22 plasma levels, which correlated with the
      disease severity. Expression of IL-22 and IL-22-regulated genes was reduced by
      anti-psoriatic therapy. In summary, despite similarities, IFN-gamma primarily
      amplifies inflammation, while IL-22 may be important in the innate immunity and
      reorganization of epithelia.

PMID- 16619291
TI  - Genetic vaccines against Ep-CAM break tolerance to self in a limited subset of
      subjects: initial identification of predictive biomarkers.
AB  - The epithelial cell adhesion molecule, Ep-CAM, has been historically considered a
      target of passive immunotherapy using monoclonal antibodies, and more recently,
      of a first Pox-vector-based cancer vaccine Phase I trial in colorectal cancer
      patients. To shed further light on the use of this antigen, we isolated the mouse
      and rhesus homologues of human Ep-CAM and explored different genetic vaccination
      modalities based on the use of adenoviral vectors as well as DNA electroporation
      (DNA-EP). Immune responses to Ep-CAM were measured by IFN-gamma ELISPOT and
      intracellular staining assays using overlapping sets of peptides covering the
      entire coding regions. We found the most powerful vaccination regimen to be
      constituted by DNA-EP-prime/Adeno-boost mixed-modality protocols. Vaccination in
      rhesus macaques resulted in breakage of immunological tolerance in a minority of
      cases. Similarly, a low frequency of responders was observed with the mouse Ep
      CAM vaccine in outbred CD1 mice. When immunized CD1 mice were analyzed for MHC
      haplotype and TCR expression levels, we observed that immune responders all had
      the same q/q MHC class I haplotype and showed higher expression levels of the
      TCRVbeta4 and TCRVbeta8 T cell receptors. Our results underscore the current
      limitations in our capacity to induce efficient cancer vaccines against self
      antigens like Ep-CAM, but also represent a first effort to identify predictive
      biomarkers of response.

PMID- 16619292
TI  - Direct role of NF-kappaB activation in Toll-like receptor-triggered HLA-DRA
      expression.
AB  - Microbial components, such as DNA containing immunostimulatory CpG motifs (CpG
      DNA) and lipopolysaccharides (LPS), elicit the cell surface expression of MHC
      class II (MHC-II) through Toll-like receptor (TLR)/IL-1R. Here, we show that CpG
      DNA and LPS induce expression of the HLA-DRA in the human B cell line, RPMI 8226.
      Ectopic expression of the dominant negative mutant of CIITA and RNA interference
      targeting the CIITA gene indicate that CIITA activation is not enough for the
      maximal MHC-II expression induced by CpG-DNA and LPS. Additionally, nuclear
      factor (NF)-kappaB activation is required for the CpG-DNA-activated and LPS
      activated HLA-DRA expression, whereas IFN-gamma-induced MHC-II expression depends
      on CIITA rather than on NF-kappaB. Comprehensive mutant analyses, electrophoretic
      mobility shift assays and chromatin immunoprecipitation assays, reveal that the
      functional interaction of NF-kappaB with the promoter element is necessary for
      the TLR-mediated HLA-DRA induction by CpG-DNA and LPS. This novel mechanism
      provides the regulation of MHC-II gene expression with complexity and functional
      diversity.

PMID- 16619293
TI  - Carbohydrate-independent recognition of collagens by the macrophage mannose
      receptor.
AB  - Mannose receptor (MR) is the best characterised member of a family of four
      endocytic molecules that share a common domain structure; a cysteine-rich (CR)
      domain, a fibronectin-type II (FNII) domain and tandemly arranged C-type lectin
      like domains (CTLD, eight in the case of MR). Two distinct lectin activities have
      been described for MR. The CR domain recognises sulphated carbohydrates while the
      CTLD mediate binding to mannose, fucose or N-acetylglucosamine. FNII domains are
      known to be important for collagen binding and this has been studied in the
      context of two members of the MR family, Endo180 and the phospholipase A2
      receptor. Here, we have investigated whether the broad and effective lectin
      activity mediated by the CR domain and CTLD of MR is favoured to the detriment of
      FNII-mediated interaction(s). We show that MR is able to bind and internalise
      collagen in a carbohydrate-independent manner and that MR deficient macrophages
      have a marked defect in collagen IV and gelatin internalisation. These data have
      major implications at the molecular level as there are now three distinct ligand
      binding sites described for MR. Furthermore our findings extend the range of
      endogenous ligands recognised by MR, a molecule firmly placed at the interface
      between homeostasis and immunity.

PMID- 16619294
TI  - dUTP Pyrophosphatase, its appearance in extracellular compartment may serve as a
      potential biomarker for N-methyl-N'-nitro-N-nitrosoguanidine exposure in
      mammalian cells.
AB  - The monofunctional alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)
      is a model chemical widely used for studying the molecular events induced by the
      widespread environmental N-nitroso alkylating carcinogen. Many studies have
      focused on understanding MNNG-induced mutagenesis and carcinogenesis. However,
      the search for specific indicators of MNNG exposure is still underway. In this
      study, we analyzed the proteins in culture medium of human amnion epithelial
      cells (FL cells) exposed to MNNG by 2-DE followed by MALDI-TOF MS, in the hope of
      finding a specific protein marker suitable for MNNG risk assessment. Image
      visualization and statistical analysis indicated that 12 spots appeared and 4
      spots up-regulated after MNNG exposure. Most of them were identified by MS. These
      proteins include nuclear isoform of dUTP pyrophosphatase (DUT-N),
      phosphoglycerate mutase 1, heparan sulfate proteoglycan perlecan, etc., which are
      involved in multiple cellular functions. Interestingly, 2-DE and MS analyses of
      cell lysate exposed to MNNG revealed that DUT-N was down-regulated. The
      appearance of DUT-N in culture medium and its down-regulation in cell lysate was
      confirmed by Western blot. These data suggest that these proteins, especially DUT
      N, could be used as candidate biomarkers for monitoring MNNG exposure.

PMID- 16619295
TI  - Resolution and characterisation of multiple isoforms of bovine kappa-casein by 2
      DE following a reversible cysteine-tagging enrichment strategy.
AB  - Visualisation of multiple isoforms of kappa-casein on 2-D gels is restricted by
      the abundant alpha- and beta-caseins that not only limit gel loading but also
      migrate to similar regions as the more acidic kappa-casein isoforms. To overcome
      this problem, we took advantage of the absence of cysteine residues in alpha(S1)-
      and beta-casein by devising an affinity enrichment procedure based on reversible
      biotinylation of cysteine residues. Affinity capture of cysteine-containing
      proteins on avidin allowed the removal of the vast majority of alpha(S1)- and
      beta-casein, and on subsequent 2-D gel analysis 16 gel spots were identified as
      kappa-casein by PMF. Further analysis of the C-terminal tryptic peptide along
      with structural predictions based on mobility on the 2-D gel allowed us to assign
      identities to each spot in terms of genetic variant (A or B), phosphorylation
      status (1, 2 or 3) and glycosylation status (from 0 to 6). Eight isoforms of the
      A and B variants with the same PTMs were observed. When the casein fraction of
      milk from a single cow, homozygous for the B variant of kappa-casein, was used as
      the starting material, 17 isoforms from 13 gel spots were characterised. Analysis
      of isoforms of low abundance proved challenging due to the low amount of material
      that could be extracted from the gels as well as the lability of the PTMs during
      MS analysis. However, we were able to identify a previously unrecognised site,
      T(166), that could be phosphorylated or glycosylated. Despite many decades of
      analysis of milk proteins, the reasons for this high level of heterogeneity are
      still not clear.

PMID- 16619296
TI  - Proteomics analysis of a novel compound: cyclic RGD in breast carcinoma cell line
      MCF-7.
AB  - In studies of cell adhesion, migration, growth, differentiation, and apoptosis,
      synthetic peptides containing the RGD (Arg-Gly-Asp) motif have been extensively
      used as the inhibitors of integrin-ligand interactions. The RGD motif is an
      integrin-recognition motif found in many ligands, so that the RGD-containing
      peptides can be used to probe integrin functions in various biological systems. A
      linear RGD is a tripeptide consisting of a flexible structure that makes the
      motif bind to its receptor with inefficient chelating affinity. Therefore, we
      designed a cyclic-RGD peptide (Tpa-RGDWPC, cRGD) with rigid skeleton to closely
      bind with its receptor. The cRGD was obtained by solid-phase peptide synthesis
      method using Rink amide resin. We showed that the cRGD exerts more potency than
      linear RGD on inhibiting cell growth of MCF-7 breast carcinoma cells. This
      stimulated us to question how cRGD inhibits cell growth of MCF-7 cells. Moreover,
      understanding what molecular mechanism underlies the effect that RGD motif exerts
      on MCF-7 cells is also of considerable importance. We used proteomics and
      bioinformatics to survey the global changes in proteins after cRGD treatment in
      MCF-7 cells. The classification of these proteins is shown according to the
      different biological processes in which they are involved. Most of the proteins
      that appear to be strongly influenced by cRGD treatment are involved in
      metabolism, cell growth, responsive to external stimulus, cell communication,
      reproduction and cell death. This is the first report which monitors the protein
      expression profile of MCF-7 cells in response to treatment with RGD-containing
      peptides in a time-course analysis. The clustering data indicated temporal
      patterns of altered protein expression that can be categorized into early,
      intermediate and late response proteins. These patterns of protein expression may
      be important for predicting its response to cRGD. In summary, these results
      provide a molecular explanation for the properties of cRGD in breast cancer cells
      and present a valuable in-depth description of their possible impact on breast
      cancer therapy.

PMID- 16619297
TI  - Conformational separation of monosaccharides of glycoproteins labeled with 2
      aminoacrydone using microchip electrophoresis.
AB  - The conformational separation of monosaccharides labeled with fluorescent 2
      aminoacrydone (AMAC) was performed by electrophoresis on a plastic microchip with
      light-emitting diode confocal fluorescence detection. The AMAC-labeled five
      neutral monosaccharide mixture (D-glucose (Glc), D-mannose, D-galactose, L
      fucose, and D-xylose) or two amino monosaccharide mixture (N-acetyl-D-glucosamine
      and N-acetyl-D-galactosamine) were well separated at pH 8.5 and 0.5% w/v
      methylcellulose of 200 mM borate buffer conditions using microchip
      electrophoresis. The separation was successfully performed considering the
      difference in stability of the complex between the hydroxyl residue of the
      monosaccharide and borate ions, and we found that 200 mM and pH 8.5 of borate
      buffer conditions were critical. High-speed separation for the neutral
      monosaccharides (50 s) and for amino monosaccharides (70 s) was attained at a 400
      V/cm of electric field condition, showing all peak resolutions were greater than
      0.9% and RSD of mobility were less than 1.9%. The detection limits of 0.86 microM
      for Glc and <1 microM for all other monosaccharides were enhanced with the
      addition of 0.5% w/v methylcellulose to the buffer. These attainments are fully
      compatible with conventional CE. The analysis of the subtle differences in the
      conformational stability and the value of the hydroxyl residue of the borate
      complex allowed the development of an efficient prospective tool for attaining
      high-resolution separation of monosaccharide mixtures having complicated and
      analogous conformations.

PMID- 16619298
TI  - Evaluation of sieving matrices used to separate alleles by cycling temperature
      capillary electrophoresis.
AB  - Denaturing CE (DCE) is a powerful tool for analysis of DNA variation. The
      development of commercial multi-CE instruments allows large-scale studies of DNA
      variation (many samples and many fragments). However, the cost of consumables
      like capillary arrays and sieving matrix might limit the use of DCE in such
      studies. Thus, we have tested 72 different in-house formulated sieving matrices'
      ability to suppress EOF and separate PCR-amplified alleles with the DCE variant,
      cycling temperature CE (CTCE). The data herein demonstrate that alleles can be
      baseline-separated by use of PVP and poly(N,N-dimethyl acrylamide) polymers at
      various percentages and pH. Allele separation by CTCE is matrix-independent and
      consequently applicable to any capillary instrument used for DNA separation.
      Formulation of sieving matrix for CTCE was done by dissolving appropriate amount
      of polymer powder into the running buffers. Allele separation was observed at
      different pH (7.5-8.5), concentrations and molecular size of the polymer, without
      compromising the separation and reproducibility. Finally, the cost reduction of
      homemade matrices is more than 1000-fold as compared to commercial sieving
      matrices.

PMID- 16619299
TI  - Numerical modeling of the Joule heating effect on electrokinetic flow focusing.
AB  - In electrokinetically driven microfluidic systems, the driving voltage applied
      during operation tends to induce a Joule heating effect in the buffer solution.
      This heat source alters the solution's characteristics and changes both the
      electrical potential field and the velocity field during the transport process.
      This study performs a series of numerical simulations to investigate the Joule
      heating effect and analyzes its influence on the electrokinetic focusing
      performance. The results indicate that the Joule heating effect causes the
      diffusion coefficient of the sample to increase, the potential distribution to
      change, and the flow velocity field to adopt a nonuniform profile. These
      variations are particularly pronounced under tighter focusing conditions and at
      higher applied electrical intensities. In numerical investigations, it is found
      that the focused bandwidth broadens because thermal diffusion effect is enhanced
      by Joule heating. The variation in the potential distribution induces a
      nonuniform flow field and causes the focused bandwidth to tighten and broaden
      alternately as a result of the convex and concave velocity flow profiles,
      respectively. The present results confirm that the Joule heating effect exerts a
      considerable influence on the electrokinetic focusing ratio.

PMID- 16619300
TI  - Determination of tobramycin in human serum by capillary electrophoresis with
      contactless conductivity detection.
AB  - A study on the determination of the antibiotic tobramycin by CE with capacitively
      coupled contactless conductivity detection is presented. This method enabled the
      direct quantification of the non-UV-absorbing species without incurring the
      disadvantages of the indirect approaches which would be needed for optical
      detection. The separation of tobramycin from inorganic cations present in serum
      samples was achieved by optimizing the composition of the acetic acid buffer.
      Field-amplified sample stacking was employed to enhance the sensitivity of the
      method and a detection limit of 50 microg/L (S/N = 3) was reached. The RSDs
      obtained for migration time and peak area using kanamycin B as internal standard
      were typically 0.12 and 4%, respectively. The newly developed method was
      validated by measuring the concentration of tobramycin in serum standards
      containing typical therapeutic concentrations of 2 and 10 mg/L. The recoveries
      were 96 and 97% for the two concentrations, respectively.

PMID- 16619301
TI  - Application of poly(methacrylic acid-ethylene glycol dimethacrylate) monolith
      microextraction coupled with capillary zone electrophoresis to the determination
      of opiates in human urine.
AB  - A novel poly(methacrylic acid-ethylene glycol dimethacrylate) (MAA-EGDMA)
      monolith microextraction method coupled with CZE was proposed for rapidly
      determining a mixture of opiates comprising heroin, 6-monoacetylmorphine,
      morphine, codeine, papaverine, and narcotine in human urine. The extraction
      device contained a regular plastic syringe, the poly(MAA-EGDMA) monolithic
      capillary tube (530 microm id x 3 cm) and a plastic pinhead, which connected the
      monolithic capillary tube and the syringe without leakage. In the polymer
      monolith microextraction, the sample solution was ejected via the monolithic
      capillary tube by a programmable syringe pump, followed by desorption with an
      aliquot of appropriate solution, which was collected into a vial for the
      subsequent analysis by CZE. The best separation was achieved using a buffer
      composed of 0.1 M disodium hydrogen phosphate (adjusted to pH 4.5 with 1 M
      hydrochloric acid) and 20% methanol v/v with temperature and voltage of 25
      degrees C and 25 kV, respectively. By applying electrokinetic injection with
      field-enhanced sample stacking, detection limits of 6.6-19.5 ng/mL were achieved.
      Excellent method of reproducibility was found over a linear range of 80-2000
      ng/mL.

PMID- 16619302
TI  - Proteomic identification of glucocorticoid receptor interacting proteins.
AB  - The glucocorticoid receptor (GR) acts as a ligand dependent transcription factor
      but can also cross talk with other signaling pathways via protein-protein
      interactions. In this paper we describe methods to study novel cytosolic GR
      interacting proteins, using mAb based immunoaffinity chromatography of GR from
      rat liver cytosol. Co-purifying proteins were identified by 2-DE in combination
      with MALDI-TOF-MS. Non-liganded/non-activated and in vitro liganded/activated GR,
      respectively, co-purifies with specific sets of proteins. Of these 34 were
      conclusively identified, seven have previously been reported to be part of the GR
      complex, revealing 27 new possible interacting candidates for the GR-complex. Of
      the novel GR interacting proteins the major vault protein, TATA binding
      interacting protein 49a and glycoprotein PP63 were of special interest.
      Furthermore, using 2-D DIGE we show that the set of proteins interacting with non
      liganded GR is distinctly different in protein amount compared to the proteins
      found with liganded/activated GR. This suggests the presence of different GR
      complexes in the cell, which was further substantiated by the finding of several
      separate GR native protein complexes, "GR-receptosomes", using blue native gel
      electrophoresis. Our findings suggest the existence of several new mechanisms for
      GR signaling and regulation.

PMID- 16619303
TI  - Proteomic analysis of the transition from quiescent to proliferating stages in
      rat liver hepatectomy model.
AB  - The 70% (or 2/3) partial hepatectomy (PHx) rat liver model provides an effective
      medium for study of the transition and regulation of hepatocytes from quiescent
      to proliferating phase. Although the gene expression pattern has come under
      intense scrutiny, a differential proteomic study could help to reveal the
      mechanism of how the process is initiated and regulated. The proteomic changes
      were analyzed in two groups, 7 h after 70% PHx test group and sham-operation
      control group, by two-dimensional gel electrophoresis with 907 +/- 33 and 910 +/-
      64 spots on gels, respectively. Twelve down-regulated spots and twenty-six up
      regulated spots were recognized using ImageMaster software and were identified by
      matrix-assisted laser desorption/ionization-mass spectrometry-quadrupole time of
      flight mass spectrometry and/or tandem mass spectrometry reconfirmation. Some of
      the differential proteins were associated with stress defense, lipid metabolism,
      and macromolecular biosynthesis while the others were shown to be involved in
      regulating transcript factors associated with liver regeneration. A "proteomic
      model" for liver regeneration was suggested based on our data and related
      scientific literature to interpret the differential proteome pattern that
      reflected the transition of cells from quiescent to proliferating state,
      including but not limited to the rat liver after 70% PHx.

PMID- 16619304
TI  - Optimising ovine cerebrospinal fluid preparation for two-dimensional gel
      electrophoresis.
AB  - Biomarkers for neurodegenerative disorders are potentially present in
      cerebrospinal fluid (CSF) and can be detected using proteomic technologies. Since
      CSF is high in salt and low in protein, its study by proteomic methods requires
      appropriate sample preparation. In this study, we applied four different sample
      treatments to the same ovine CSF sample. Precipitation with acetone or using a 2
      D Clean-Up Kit (GE Healthcare BioSciences, Little Chalfont, UK) preserved more
      proteins, and produced more gel spots than spin columns from Sigma and Bio-Rad. A
      53-kDa spot, identified by MS/MS as transthyretin (TTR) tetramer, was not
      detected in samples treated with the 2-D Clean-Up Kit, though it was always
      present on all gels prepared using the other three methods. Western
      immunoblotting confirmed the low recovery of tetrameric TTR by the 2-D Clean-Up
      Kit and showed that the tetrameric form of TTR predominated in ovine but not in
      rat CSF. In one ovine CSF sample haemoglobin was found, indicating blood
      contamination. We conclude that acetone precipitation is a simple and efficient
      way to prepare ovine CSF for 2-DE. The use of the 2-D Clean-Up Kit leads to the
      disappearance of tetrameric TTR only from ovine CSF proteome.

PMID- 16619305
TI  - Proteomic pattern-based analyses of light responses in Arabidopsis thaliana wild
      type and photoreceptor mutants.
AB  - Light critically affects the physiology of plants. Using two-dimensional gel
      electrophoresis, we used a proteomics approach to analyze the responses of
      Arabidopsis thaliana to red (660 nm), far-red (730 nm) and blue (450 nm) light,
      which are utilized by type II and type I phytochromes, and blue light receptors,
      respectively. Under specific light treatments, the proteomic profiles of 49
      protein spots exhibited over 1.8-fold difference in protein abundance,
      significant at p <0.05. Most of these proteins were metabolic enzymes, indicating
      metabolic changes induced by light of specific wavelengths. The differentially
      expressed proteins formed seven clusters, reflecting co-regulation. We used the
      49 differentially-regulated proteins as molecular markers for plant responses to
      light, and by developing a procedure that calculates the Pearson correlation
      distance of cluster-to-cluster similarity in expression changes, we assessed the
      proteome-based relatedness of light responses for wild-type and phytochrome
      mutant plants. Overall, this assessment was consistent with the known
      physiological responses of plants to light. However, we also observed a number of
      novel responses at the proteomic level, which were not predicted from known
      physiological changes.

PMID- 16619306
TI  - Depletion of abundant proteins from non-human primate serum for biomarker
      studies.
AB  - Non-human primates are an important biomedical research model organism and offer
      great promise for serum biomarker proteomic studies. However, potential obstacles
      to these studies include affinity serum depletion methods based on human
      antigens, depletion methods altering quantitation, and incomplete non-human
      primate genome sequences for protein identification. In the present study, high
      abundance protein removal from monkey serum using a human multiple affinity
      removal system (MARS) was shown to be specific and did not alter quantitation.
      Depleted serum also demonstrated greater sensitivity for previously masked, lower
      abundance proteins.

PMID- 16619307
TI  - Pathway alterations during glioma progression revealed by reverse phase protein
      lysate arrays.
AB  - The progression of gliomas has been extensively studied at the genomic level
      using cDNA microarrays. However, systematic examinations at the protein
      translational and post-translational levels are far more limited. We constructed
      a glioma protein lysate array from 82 different primary glioma tissues, and
      surveyed the expression and phosphorylation of 46 different proteins involved in
      signaling pathways of cell proliferation, cell survival, apoptosis, angiogenesis,
      and cell invasion. An analysis algorithm was employed to robustly estimate the
      protein expressions in these samples. When ranked by their discriminating power
      to separate 37 glioblastomas (high-grade gliomas) from 45 lower-grade gliomas,
      the following 12 proteins were identified as the most powerful discriminators:
      IBalpha, EGFRpTyr845, AKTpThr308, phosphatidylinositol 3-kinase (PI3K),
      BadpSer136, insulin-like growth factor binding protein (IGFBP) 2, IGFBP5, matrix
      metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF),
      phosphorylated retinoblastoma protein (pRB), Bcl-2, and c-Abl. Clustering
      analysis showed a close link between PI3K and AKTpThr308, IGFBP5 and IGFBP2, and
      IBalpha and EGFRpTyr845. Another cluster includes MMP9, Bcl-2, VEGF, and pRB.
      These clustering patterns may suggest functional relationships, which warrant
      further investigation. The marked association of phosphorylation of AKT at
      Thr308, but not Ser473, with glioblastoma suggests a specific event of PI3K
      pathway activation in glioma progression.

PMID- 16619308
TI  - Targeted proteomics in biomarker validation: detection and quantification of
      proteins using a multi-dimensional peptide separation strategy.
AB  - Authentic biomarkers, distilling the essence of a complex, functionally
      significant process in a mammalian system into a precise, physicochemical
      measurement have been implicated as a tool of increasing importance for drug
      discovery and development. However, even in spite of recent technological
      advances, validating a new biomarker candidate, where generation of suitable
      antibodies is required, is still a long-lasting task. Methods to accelerate
      initial validation by MS approaches have been suggested, but all methods
      described so far are associated with serious drawbacks, finally leading to non
      generic methods of detection and quantification. Moreover, when complex body
      fluids are used as samples, efficient debulking strategies are crucial to open a
      window of analytical sensitivity in the ng/mL range, where many diagnostically
      relevant analytes are present. Here we report the proof-of-principle of a multi
      dimensional strategy for accelerated initial validation of biomarker candidates
      by MS, which promises to be generally applicable, sensitive and quantitative. The
      method presented employs a combination of electrophoretic and chromatographic
      steps on the peptide level, followed by MS quantification using isotopically
      labeled synthetic peptides as internal standards. Our proposed workflow includes
      up to four dimensions, finally resulting in a desired LOD sufficient to detect
      and quantify diagnostically relevant analytes from complex samples. Although the
      current state of the method only represents a starting point for further
      validation and development, it reveals great potential in biomarker validation.

PMID- 16619309
TI  - Changes in liver protein abundance in inbred alcohol-preferring rats due to
      chronic alcohol exposure, as measured through a proteomics approach.
AB  - This study compares the total liver proteome of inbred alcohol-preferring line
      (iP) rats exposed to alcohol with iP rats without alcohol experience. Rat liver
      proteins were extracted using a three-step procedure. Each of the three solutions
      solubilizes a different set of proteins. The extracted proteins were separated by
      2-DE. Scanned gels of two sample groups, alcohol-exposed iP and alcohol-naive iP,
      were compared, revealing many protein spots with significantly higher or lower
      densities. These spots were cut from the gel, destained, and subjected to trypsin
      digestion and subsequent identification by LC-MS/MS. Twenty-four individual rats,
      12 alcohol-naive, and 12 alcohol-exposed, were used in this study. Two groups,
      each containing six naive and six exposed animals, were created for statistical
      comparison. For the first group, 64 spots were observed to have statistically
      significant intensity differences upon alcohol exposure across all three extracts
      while 118 such spots were found in the second group. There were 113 unique
      proteins in both groups together. The majority of these proteins were enzymes.
      Significant changes are observed for three major metabolic pathways: glycolysis,
      gluconeogenesis, and fatty acid beta-oxidation. In addition, enzymes involved in
      protein synthesis and antioxidant activity show significant changes in abundance
      in response to alcohol exposure.

PMID- 16619310
TI  - Proteomic analysis of the 14-3-3 family in Arabidopsis.
AB  - In this study, various proteomics-based methods were utilized to examine the 14-3
      3 protein family in Arabidopsis thaliana. A protein extract was prepared from an
      Arabidopsis hypocotyl suspension culture and analyzed by two-dimensional gel
      electrophoresis and immunoblotting with a 14-3-3 monoclonal antibody that
      recognizes multiple Arabidopsis isoforms. Protein spots that cross-reacted with
      the monoclonal antibody as well as the surrounding spots were analyzed by high
      performance liquid chromatography in conjunction with electrospray-tandem mass
      spectrometry. Nine separate spots contained 14-3-3s and each spot contained
      multiple 14-3-3 isoforms. Every isoform observed was verified by the
      identification of at least one isoform-specific peptide. Further analysis by mass
      spectrometry revealed that the isoforms Chi, Upsilon, Omega, Phi, and Lambda were
      acetylated on their N termini and no non-acetylated N termini were recovered.
      These data, together with the distribution of isoforms and the confirmation that
      14-3-3s are not complexed during urea denaturing isoelectric focusing, supports
      the conclusion that Arabidopsis 14-3-3s are acetylated in vivo and are
      significantly affected by other post-translational modifications.

PMID- 16619311
TI  - Out of Cordoba.

PMID- 16619312
TI  - A direct electrochemical route from ilmenite to hydrogen-storage ferrotitanium
      alloys.
AB  - An unrecognised but predictable need for a hydrogen-supported society is tens or
      even hundreds of million tonnes of hydrogen-storage materials, and thus
      challenges existing technologies in terms of resource and economical realities.
      Ilmenite is an abundant mineral, and ferrotitanium alloys are among the earliest
      known hydrogen-storage materials. At present, industrial production of
      ferrotitanium alloys goes through separate extraction of individual metals,
      followed by a multistep arc-melting process. In particular, the extraction of
      titanium from ilmenite is highly energy intensive and tedious, accounting for
      titanium's high market price and restricted uses. This article reports the
      electrochemical synthesis of various ferrotitanium alloy powders directly from
      solid ilmenite in molten calcium chloride. More importantly, it demonstrates, for
      the first time, that such produced alloy powders can be used without further
      treatment for hydrogen storage and perform comparably with or better than similar
      products by means of other methods, but cost just a fraction.

PMID- 16619314
TI  - Novel mu5-coordination modes of aryl and alkyl ethynides and classification of
      metal-ligand interactions in silver(I) complexes.
AB  - Novel mu(5)-eta(1),eta(1),eta(1),eta(1),eta(2) and mu(5)
      eta(1),eta(1),eta(1),eta(2),eta(2) coordination modes of alkyl and aryl ethynide
      moieties are found in silver(I) complexes 1-5, and the metal-ligand distances can
      be classified into sigma, pi and mixed (sigma,pi) types. With the consistent
      square-pyramidal capping Ag(5) baskets of the ethynide moiety as supramolecular
      synthons, a series of two- and three-dimensional coordination networks are
      obtained.

PMID- 16619313
TI  - Effective manipulation of the electronic effects and its influence on the
      emission of 5-substituted tris(8-quinolinolate) aluminum(III) complexes.
AB  - The unique electron-transport and emissive properties of tris(8-quinolinolate)
      aluminum(III) (Alq(3)) have resulted in extensive use of this material for small
      molecular organic light-emitting diode (OLED) fabrication. So far, efforts to
      prepare stable and easy-to-process red/green/blue (RGB)-emitting Alq(3)
      derivatives have met with only a limited success. In this paper, we describe how
      the electronic nature of various substituents, projected via an arylethynyl or
      aryl spacer to the position of the highest HOMO density (C5), may be used for
      effective emission tuning to obtain blue-, green-, and red-emitting materials.
      The synthetic strategy consists of four different pathways for the attachment of
      electron-donating and electron-withdrawing aryl or arylethynyl substituents to
      the 5-position of the quinolinolate ring. Successful tuning of the emission color
      covering the whole visible spectrum (lambda=450-800 nm) was achieved. In
      addition, the photophysical properties of the luminophores were found to
      correlate with the Hammett constant of the respective substituents, providing a
      powerful strategy with which to predict the optical properties of new materials.
      We also demonstrate that the electronic nature of the substituent affects the
      emission properties of the resulting complex through effective modification of
      the HOMO levels of the quinolinolate ligand.

PMID- 16619315
TI  - Monomeric azaheterofullerene derivatives RC59N: influence of the R moiety on
      spectroscopic and photophysical properties.
AB  - We have synthesised nine monomeric azaheterofullerene (AZA) derivatives, RC(59)N,
      with a wide variety of different side chains R and investigated their
      spectroscopic and photophysical properties in toluene and o-dichlorobenzene
      (ODCB). Measurements include their ground-state absorption spectra, molar
      absorption coefficient (epsilon(G)), fluorescence spectra, fluorescence quantum
      yields (Phi(F)), singlet-state lifetimes (tau(F)), triplet-state absorption
      spectra, triplet molar absorption coefficients (epsilon(T)), singlet oxygen
      (Phi(Delta)), and triplet state (Phi(T)) quantum yields. The replacement of a
      carbon by a nitrogen atom in the C(60) sphere strongly affects most of the
      spectroscopic and photophysical properties. The chemical nature of the R moiety
      has definite effects on these properties in contrast with minor effects on the
      chemical nature of the addends in [6,6]-ring bridged monoadduct
      methano[60]fullerene derivatives. These effects concern properties of the ground
      state, singlet excited state, and triplet states of our nine RC(59)N derivatives
      and in particular the values of photophysical parameters epsilon(G), epsilon(T),
      Phi(Delta), and Phi(T), which are significantly lower than those of analogous
      monoadduct [6,6]-ring bridged methano[60]fullerene derivatives.

PMID- 16619316
TI  - Total synthesis of phoslactomycin B and its biosynthetic deamino precursor.

PMID- 16619317
TI  - Nonconventional catalysts for isotactic propene polymerization in solution
      developed by using high-throughput-screening technologies.

PMID- 16619318
TI  - Evolution of nano- to microsized spherical assemblies of a short oligo(p
      phenyleneethynylene) into superstructured organogels.

PMID- 16619319
TI  - Gold-catalyzed intermolecular hydroamination of allenes with arylamines and
      resulting high chirality transfer.

PMID- 16619320
TI  - Lanthanide complexes of the monovacant Dawson polyoxotungstate [alpha1
      P2W17O61]10- as selective and recoverable Lewis acid catalysts.

PMID- 16619321
TI  - To the core of autocatalysis in cyclohexane autoxidation.
AB  - Despite their industrial importance, the detailed reaction mechanism of
      autoxidation reactions is still insufficiently known. In this work, complementary
      experimental and theoretical techniques are employed to address the radical-chain
      initiation in the autoxidation of cyclohexane with a particular focus on the
      "lighting-off" of the oxidation by (added) cyclohexanone. We used a newly
      developed method to quantify the intrinsic rate of chain initiation as well as
      the rate enhancement by cyclohexanone and several other (oxygenated) molecules.
      On the basis of first principles, the hitherto assumed perhemiketale mechanism
      was found to be many orders of magnitude too slow to account for the observed
      initiation enhancement by the ketone. Instead, it is shown that the pronounced
      chain-initiation enhancement by the ketone is attributable to a newly proposed
      concerted reaction between cyclohexyl hydroperoxide and cyclohexanone, in which
      the (.)OH radical breaking away from the hydroperoxide abstracts an alphaH atom
      from the ketone, thereby energetically assisting in the cleavage of the RO--OH
      bond. This reaction is highly efficient in generating radicals as it quasi
      excludes geminate in-cage recombination. As a result, the ketone oxidation
      product at a level of 1 mol % increases the initiation rate by one order of
      magnitude, and so acts as a highly efficient "autocatalyst" in autoxidation
      reactions. An analogous reaction with cyclohexanol, although estimated to be even
      faster, has only a marginal effect on the overall kinetics, owing to the fast
      subsequent formation of HO(2) (.) radicals that very rapidly terminate with other
      ROO(.) radicals. Finally, solid evidence is presented that, also in absence of
      oxygenates, ROOH initiation is actually a bimolecular reaction, involving
      concerted H abstraction from the alkane substrate by the nascent (.)OH.

PMID- 16619322
TI  - Why are proteins charged? Networks of charge-charge interactions in proteins
      measured by charge ladders and capillary electrophoresis.
AB  - Almost all proteins contain charged amino acids. While the function in catalysis
      or binding of individual charges in the active site can often be identified, it
      is less clear how to assign function to charges beyond this region. Are they
      necessary for solubility? For reasons other than solubility? Can manipulating
      these charges change the properties of proteins? A combination of capillary
      electrophoresis (CE) and protein charge ladders makes it possible to study the
      roles of charged residues on the surface of proteins outside the active site.
      This method involves chemical modification of those residues to generate a large
      number of derivatives of the protein that differ in charge. CE separates those
      derivatives into groups with the same number of modified charged groups. By
      studying the influence of charge on the properties of proteins using charge
      ladders, it is possible to estimate the net charge and hydrodynamic radius and to
      infer the role of charged residues in ligand binding and protein folding.

PMID- 16619323
TI  - Lydiamycins A-D: cyclodepsipetides with antimycobacterial properties.

PMID- 16619324
TI  - C30H12(6-): self-aggregation, high charge density, and pyramidalization in a
      supramolecular structure of a supercharged hemifullerene.

PMID- 16619325
TI  - Direct protein identification from nonspecific peptide pools by high-accuracy MS
      data filtering.

PMID- 16619326
TI  - Charge separation at self-assembled nanostructured bulk interface in block
      copolymers.

PMID- 16619327
TI  - Structure-sensitive and self-assembled helical pyrene array based on DNA
      architecture.

PMID- 16619328
TI  - A Co2N2 diamond-core resting state of cobalt(I): a three-coordinate CoI synthon
      invoking an unusual pincer-type rearrangement.

PMID- 16619329
TI  - Synthesis of a rhodaazacyclopropane and characterization of its radical cation by
      EPR spectroscopy.

PMID- 16619330
TI  - Solid-phase enzyme activity assay utilizing an entrapped fluorescence-signaling
      DNA aptamer.

PMID- 16619331
TI  - Reversible photocontrol of deoxyribozyme-catalyzed RNA cleavage under multiple
      turnover conditions.

PMID- 16619332
TI  - Inhibition of rat platelet aggregation by Urtica dioica leaves extracts.
AB  - Platelet hyperactivity plays an important role in arterial thrombosis and
      atherosclerosis. The present study was undertaken to investigate the effects of
      different extracts of Urtica dioica leaves on platelet aggregation. Rat platelets
      were prepared and incubated in vitro with different concentrations of the tested
      extracts and aggregation was induced by different agonists including thrombin
      (0.5 U/mL), ADP (10 microm), epinephrine (100 microm) and collagen (5 mg/mL). The
      crude aqueous extract inhibited thrombin-induced platelet aggregation in a dose
      dependent manner. At 1 mg/mL, the percent inhibition was 17.1 +/- 4.2%. Soxhlet
      extraction of the plant leaves with different successive solvents showed that the
      ethyl acetate extract exhibited the most antiaggregant effect with an inhibition
      of 76.8 +/- 6.1% at 1 mg/mL. Flavonoids isolated from the plant leaves, produced
      a strong inhibitory effect on thrombin-induced platelet aggregation with an
      IC(50) of 0.25 +/- 0.05 and 0.40 +/- 0.04 mg/mL for genins and heterosidic
      flavonoids, respectively. Flavonoids also markedly inhibited platelet aggregation
      induced by ADP, collagen and epinephrine. It is concluded that Urtica dioica has
      an antiplatelet action in which flavonoids are mainly implicated. These results
      support the traditional use of Urtica dioica in the treatment and/or prevention
      of cardiovascular disease.

PMID- 16619333
TI  - Antioxidant activity of wild plants collected in Valsesia, an alpine region of
      Northern Italy.
AB  - A selection of wild plants collected in Valsesia (Northwest Italy) was screened
      for their in vitro antioxidant activity. Aerial parts of selected plants were
      dried at room temperature and powdered. Then, four sequential extractions were
      performed with increasing polarity solvents, i.e. n-hexane, chloroform,
      chloroform-methanol (9:1, v/v) and methanol. By employing different assays, it
      was shown that all the methanol extracts of the samples collected were endowed
      with antioxidant activity, though, as expected, their potency varied according to
      the different tests. In particular, plants of the Thymus and Achillea genus
      displayed the highest activity. Given that a diet rich in wild plants is
      associated with a reduced incidence of degenerative diseases, such as
      atherosclerosis and cancer, this study suggests that some Valsesia plants could
      be pharmaceutically exploited.

PMID- 16619334
TI  - Characterization of an insecticidal coumarin from Boenninghausenia albiflora.
AB  - The leaves of Boenninghausenia albiflora afforded an insecticidal coumarin which
      was identified as murraxocin (7-methoxy-8-[1'-ethoxy-2'-hydroxy-3'-methyl-but
      3'enyl]-coumarin) (1), on the basis of extensive 1- and 2-dimensional NMR
      experiments. This compound has previously been isolated from Murraya exotica but
      this is the first report of the full (1)H and (13)C data for this compound. This
      natural product was evaluated against important forest insect pests and was
      active against Plecoptera reflexa, Clostera cupreata and Crypsiptya coclesalis at
      different concentrations varying from 1.0% to 5% w/v. In the crude extract 70%
      mortality was observed, and for compound 1 80% mortality was observed at a
      concentration of 1.0% w/v. The percentage of insect mortality increased in a dose
      dependent manner. Coumarins are poorly studied insecticides and there is
      potential to exploit this chemically simple group of natural products.

PMID- 16619335
TI  - Immunomodulatory effects of methoxylated flavonoids from two Chromolaena species:
      structure-activity relationships.
AB  - Excessive generation of reactive oxygen species (ROS) by polymorphonuclear
      leukocytes (PMNL) is involved in the pathology of many inflammatory diseases.
      Compounds isolated from natural sources with antioxidant activity can be helpful
      to inhibit and/or modulate the oxidative damage associated with PMNL-derived ROS.
      The present study investigated the relationship between the chemical structure of
      five methoxylated flavonoids, isolated from Chromolaena hirsuta and Chromolaena
      squalida, and their inhibitory activity on ROS generation by opsonized zymosan
      stimulated PMNL. The antioxidant efficacy of the studied flavonoids, assessed by
      luminol-dependent chemiluminescence, was dependent on the position and number of
      methoxy and hydroxy groups.

PMID- 16619336
TI  - Phytochemicals from traditional medicinal plants used in the treatment of
      diarrhoea: modes of action and effects on intestinal function.
AB  - Medicinal plants have been used as traditional treatments for numerous human
      diseases for thousands of years. Diarrhoeal diseases continue to be a major cause
      of morbidity and mortality throughout the world and there is renewed interest in
      the discovery of novel compounds that can be used to fight these diseases.
      Numerous studies have validated the traditional use of antidiarrhoeal medicinal
      plants by investigating the biological activity of extracts of such plants, which
      have antispasmodic effects, delay intestinal transit, suppress gut motility,
      stimulate water adsorption or reduce electrolyte secretion. Of the numerous
      phytochemicals (such as alkaloids, tannins, flavonoids and terpenes) present in
      active extracts, tannins and flavonoids are thought to be responsible for
      antidiarrhoeal activity by increasing colonic water and electrolyte reabsorption.
      Others act by inhibiting intestinal motility. As some of the active ingredients
      are potentially toxic, there is a need to evaluate the safety of plant
      preparations. A few clinical trials have evaluated the safety and tolerability of
      traditional and herbal medicine preparations used to treat diarrhoea and
      generally indicate that minimal side effects are observed. However, with the
      increased popularity of plant-derived and herbal medicines in Western society,
      the benefits and potential dangers of these medicines must be considered.

PMID- 16619337
TI  - Dang-Gui Buxue Tang produces a more potent cardioprotective effect than its
      component herb extracts and enhances glutathione status in rat heart mitochondria
      and erythrocytes.
AB  - The effects of pretreatment with Dang-Gui Buxue Tang (DBT, a decoction of
      Astragali and Angelica roots) and its component herb extracts on myocardial
      ischaemia-reperfusion (IR) injury were examined in rats ex vivo. DBT and its
      component herb extracts could protect against myocardial IR injury in a dose
      dependent manner. The more potent cardioprotection afforded by DBT pretreatment
      than that of a mixture of Astragali and Angelica root extracts was associated
      with a much higher extraction yield of active ingredients from Angelica root in
      the herbal decoction. The high level of active ingredients might increase their
      bioavailability after oral administration. DBT pretreatment could enhance
      myocardial mitochondrial as well as red blood cell (RBC) glutathione status,
      thereby increasing their resistance to oxidative stress-induced injury in rats.
      The measurement of RBC glutathione status may serve as a useful index for the
      antioxidant effect produced by DBT treatment in human subjects.

PMID- 16619338
TI  - A natural sweetener, Momordica grosvenori, attenuates the imbalance of cellular
      immune functions in alloxan-induced diabetic mice.
AB  - Momordica grosvenori (MG), a traditional medicinal herb in China used as a
      substitute sugar for obese and diabetic patients, exhibited an enhancement of
      immunity. Heme oxygenase-1 (HO-1) is among the acute phase proteins that play an
      important role in the inflammatory process and have antiinflammatory activities
      with their antioxidant properties. The hypothesis that MG could modulate an
      imbalance of the cellular immune system and prevent the progression of diabetes
      mellitus, via induction of HO-1 protein expression was investigated. Diabetes was
      induced in male Balb/c mice by intraperitoneal injection of alloxan (200 mg/kg).
      The mice were randomly assigned to non-diabetic and diabetic groups, and further
      subdivided according to their treatments: control (distilled water), low dose MG
      (150 mg/kg) and high dose MG (300 mg/kg), which were administered by gavage in 24
      h cycles over a 30 day period. MG administration effectively regulated the immune
      imbalance in diabetic mice, principally by upregulating the CD4(+) T lymphocyte
      subsets, and remodeling the intracellular cytokine profiles (reducing the
      expression of pro-inflammatory Th1 cytokines towards a beneficial Th2 pattern),
      ascribed to its induction and upregulation of HO-1. In conclusion, MG exhibited
      antidiabetic effects and may be used as a new natural drug for the treatment of
      diabetes.

PMID- 16619339
TI  - Tumor cell-selective antiproliferative effect of the extract from Morinda
      citrifolia fruits.
AB  - The methanol extract from Morinda citrifolia fruits was tested for cytotoxicity
      activity on the MTT assay. The appearance of cytotoxic changes after exposure to
      the extract was in a concentration dependent manner. The median lethal
      concentrations (LC(50)) of the extract in baby hamster kidney (BHK) cells,
      African green monkey kidney (Vero) cells and human laryngeal carcinoma (Hep2)
      cells were found to be 2.5, 3 and 5 mg/mL, respectively. A concentration of 0.1
      mg/mL of crude extract exhibited cytotoxic activity against breast cancer (MCF7)
      and neuroblastoma (LAN5) cell lines at 29% and 36%, respectively. The same
      concentration of extract showed no toxicity to Vero and very little toxicity to
      BHK (6%) and Hep2 (13%) cells.

PMID- 16619340
TI  - The pharmacological effects of Salvia species on the central nervous system.
AB  - Salvia is an important genus consisting of about 900 species in the family
      Lamiaceae. Some species of Salvia have been cultivated world wide for use in folk
      medicine and for culinary purposes. The dried root of Salvia miltiorrhiza, for
      example, has been used extensively for the treatment of coronary and
      cerebrovascular disease, sleep disorders, hepatitis, hepatocirrhosis, chronic
      renal failure, dysmenorrhea, amenorrhea, carbuncles and ulcers. S. officinalis,
      S. leriifolia, S. haematodes, S. triloba and S. divinorum are other species with
      important pharmacological effects. In this review, the pharmacological effects of
      Salvia species on the central nervous system will be reviewed. These include
      sedative and hypnotic, hallucinogenic, skeletal muscle relaxant, analgesic,
      memory enhancing, anticonvulsant, neuroprotective and antiparkinsonian activity,
      as well as the inhibition of ethanol and morphine withdrawal syndrome.

PMID- 16619341
TI  - Studies on hepatoprotective, antispasmodic and calcium antagonist activities of
      the aqueous-methanol extract of Achillea millefolium.
AB  - The crude extract of Achillea millefolium (Am.Cr) was studied for its possible
      hepatoprotective effect against d-galactosamine (d-GalN) and lipopolysaccharide
      (LPS) induced hepatitis in mice and antispasmodic effect in isolated gut
      preparations to rationalize some of the folklore uses. Co-administration of d
      GalN (700 mg/kg) and LPS (25 microg/kg) produced 100% mortality in mice. Pre
      treatment of animals with Am.Cr (300 mg/kg) reduced the mortality to 40%. Co
      administration of d-GalN (700 mg/kg) and LPS (1 microg/kg) significantly raised
      the plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      levels compared with values in the control group (p < 0.05). Pre-treatment of
      mice with Am.Cr (150-600 mg/kg) significantly prevented the toxins induced rise
      in plasma ALT and AST (p < 0.05). The hepatoprotective effect of Am.Cr was
      further verified by histopathology of the liver, which showed improved
      architecture, absence of parenchymal congestion, decreased cellular swelling and
      apoptotic cells, compared with the toxin group of animals. In isolated rabbit
      jejunum preparations, Am.Cr caused a concentration-dependent (0.3-10 mg/mL)
      relaxation of both spontaneous and K(+)-induced contractions as well as shifting
      the Ca(++) concentration-response curves (CRCs) to the right, similar to that
      caused by verapamil. These results indicate that the crude extract of Achillea
      millefolium exhibits a hepatoprotective effect, which may be partly attributed to
      its observed calcium channel blocking activity.

PMID- 16619342
TI  - Effect of aged garlic extract against methotrexate-induced damage to the small
      intestine in rats.
AB  - Methotrexate (MTX) chemotherapy is often accompanied by side effects such as
      gastrointestinal ulceration and diarrhea. The aim of this study was to examine
      histologically whether an aged garlic extract (AGE) had a protective effect on
      the small intestine of rats with MTX-induced damage. Forty male Wistar albino
      rats were randomized into experimental and control groups and divided into four
      groups of ten animals. To the first group, MTX was applied as a single dose (20
      mg/kg) intraperitoneally. To the second group, in addition to MTX application,
      AGE (250 mg/kg) was administered orally every day at the same time by
      intragastric intubation until the rats were killed. To the third group, AGE only
      was given. The fourth group was the control. All animals were killed 4 days after
      the intraperitoneal injection of MTX for histopathologic analysis and tissue MDA
      levels. Before killing, intracardiac blood was obtained from each animal to
      perform biochemical analysis (plasma lactate level). MTX was found to lead to
      damage in the jejunal tissues and to increase the MDA and lactate levels in the
      plasma. Administration of the AGE decreased the severity of jejunal damage, but
      increased MDA and lactate levels caused by MTX treatment on the other hand. These
      results suggest that AGE may protect the small intestine of rats from MTX-induced
      damage. Thus this study substantiated the thought that the protective effect of
      AGE is derived from the manner in which it interacts with crypt cells.

PMID- 16619343
TI  - Continentalic acid from Aralia continentalis shows activity against methicillin
      resistant Staphylococcus aureus.
AB  - In a continuing search for compounds with antibacterial activity against
      methicillin-resistant Staphylococcus aureus (MRSA), a chloroform extract of roots
      of Aralia continentalis was found to contain continentalic acid (CA,
      C(20)H(30)O(2)), a diterpenic acid. This compound exhibited potent activity
      against standard methicillin-susceptible Staphylococcus aureus (MSSA) as well as
      clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). It was
      determined that continentalic acid had minimum inhibitory concentrations (MICs)
      of approximately 8-16 microg/mL against S. aureus, including the MSSA and MRSA
      standard strains. Therefore, the results obtained in this study suggest that
      continentalic acid might have potential as an adjunct in the treatment of
      antibiotic-resistant bacteria.

PMID- 16619344
TI  - Effect on capillary permeability in rabbits of iridoids from Buddleia
      scordioides.
AB  - The methanol soluble fraction of the leaves of Buddleia scordioides after column
      chromatography resulted in the isolation of two known iridoid glucosides,
      catalpol and methylcatalpol. The structures were elucidated by extensive 1D-2D
      NMR spectroscopy. The structure of methylcatalpol was confirmed by single-crystal
      x-ray diffraction. These compounds showed protective activity against increased
      (both chloroform and histamine) skin vascular permeability in rabbits. The
      protective effect was measured as the reduction in leakage of Evans blue. The
      results showed that the iridoids produced a significant inhibition of
      microvascular permeability. A comparison was made between the action of the
      iridoids and a known inhibitor of vascular permeability, troxerutin (50 mg/kg).
      Methylcatalpol and catalpol were found to be less effective than troxerutin.

PMID- 16619345
TI  - Analgesic and hepatotoxic effects of Ononis spinosa L.
AB  - The present study investigated the analgesic and hepatoprotective activities of a
      water extract of Ononis spinosa L. (OS) in mice. Analgesic activity was based on
      the pain thresholds measured with the tail-flick test before administration at
      30, 90 and 150 min. The results were analysed with one-way variance analysis. The
      extract of Ononis spinosa showed analgesic activity equivalent to aspirin at 30
      and 90 min and even higher than aspirin with the 50 mg/kg dose. At a dose of 100
      mg/kg OS showed an analgesic effect equivalent to aspirin at all time points.The
      hepatoprotective influence of OS on carbon tetrachloride (CCl(4))-induced acute
      liver toxicity was also studied. The extract had no significant effect on the
      increased levels of aspartate aminotransferase (AST), alanine aminotransferase
      (ALT) and bilirubin in CCl(4) treated animals (p > 0.05). Thus, the results
      reveal that the extract of OS had no hepatoprotective effect on CCl(4)-induced
      acute liver toxicity.

PMID- 16619346
TI  - Leishmanicidal activity of Pycnoporus sanguineus.
AB  - In the search for antiparasite compounds from the Colombian flora, an active
      compound against Leishmania (Viannia) panamensis amastigotes was isolated from
      the fungi Pycnoporus sanguineus. The structural elucid-ation was achieved with
      spectroscopic methods ((1)H and (13)C NMR and MS). This compound was identified
      as ergosterol 5,8-endoperoxide.

PMID- 16619347
TI  - Antiplatelet activity of aporphine and phenanthrenoid alkaloids from Aromadendron
      elegans Blume.
AB  - Six aporphine and one phenanthrenoid alkaloids isolated from Aromadendron elegans
      Blume were investigated for their ability to inhibit arachidonic acid (AA),
      collagen and ADP induced platelet aggregation in human whole blood. The
      antiplatelet activity of the compounds was measured in vitro by the Chrono Log
      whole blood aggregometer using an electrical impedance method. Of the compounds
      tested, (-)-N-acetylnornuciferine, (-)-N-acetylanonaine and 1-(N-acetyl-N
      methylamino)ethyl-3,4,6-trimethoxy-7-hydroxyphenanthrene showed strong inhibition
      on platelet aggregation caused by all three inducers. (-)-N-acetylanonaine was
      the most effective antiplatelet compound as it inhibited both arachidonic acid,
      collagen and ADP-induced platelet aggregation with IC(50) values of 66.1, 95.1
      and 80.6 microm, respectively.

PMID- 16619348
TI  - Antimicrobial activity of common madder (Rubia tinctorum L.).
AB  - In this study, ethanol, methanol, ethyl acetate and water extracts of Rubia
      tinctorum L. (Rubiaceae) were tested for antimicrobial activity by the disc
      diffusion method. From the present study it was found that Rubia tinctorum L.
      revealed antimicrobial activity against some Gram (+) and Gram (-) bacteria,
      yeasts, filamentous fungi and actinomycetes.

PMID- 16619349
TI  - Butea superba Roxb. enhances penile erection in rats.
AB  - This study aimed to investigate the effects of ethanol extracts of Butea superba
      in increasing intracavernous pressure (ICP) in vivo. The extracts were prepared
      from fresh and dried root cores and fresh and dried root barks. Penile erection
      was induced in aged rats by electrical stimulation of the cavernous nerve.
      Cavernous smooth muscle relaxation was also observed in vitro in the presence of
      the extract, cGMP or isobutyl-methylxanthine (IBMX) alone or the extract together
      with cGMP or IBMX. The dried root core extract from Phrae was the most effective
      in increasing the ICP. The dose-response relationship study revealed a bell-shape
      curve with the maximum effective dose at 1 mg/kg. The ICP of the control and 1
      mg/kg extract-treated animals were 45.3 +/- 2.5 and 100.9 +/- 14.0 mmHg,
      respectively. The extract, cGMP and IBMX alone induced dose dependent muscle
      relaxation. B. superba significantly enhanced the effects of cGMP and IBMX. The
      results suggest that ethanol extracts of B. superba are effective in enhancing
      penile erection. The dried root core extract from Phrae is the most effective
      part with a maximal dose of 1 mg/kg. The results also suggest that B. superba may
      act through cAMP/cGMP pathways.

PMID- 16619350
TI  - Evaluation of antioxidant activity of Salix caprea flowers.
AB  - The study was aimed at evaluating the antioxidant activity of an ethanol extract
      of Salix caprea L. (Salicaceae) flowers. The extract was found to possess a large
      amount of polyphenols and also exhibited a high reducing ability. The extract
      significantly and dose dependently scavenged DPPH, superoxide (O(2) (*-)),
      hydrogen peroxide (H(2)O(2)) and nitric oxide (NO). At a concentration of 250
      microg/mL, 85.04% of DPPH radicals and at 500 microg/mL 45.97%, 17.97% and 56.53%
      of O(2) (*-), H(2)O(2) and NO, respectively, were scavenged by the S. caprea
      flower extract. A significant amount of protection was also afforded by the
      extract in the acute oxidative tissue injury animal model constituted by ferric
      nitrilotriacetate (FeNTA) induced hepatotoxicity in mice. An intraperitoneal
      administration of FeNTA at a dose of 9 mg/kg of body weight caused an elevation
      in hepatic lipid peroxidation (LPO) to 176.90% and a suppression in hepatic
      glutathione (GSH) content and the activities of antioxidant enzymes namely,
      catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPX) to
      46.49%, 64.37%, 41.71% and 48.76%, respectively, of the saline treated control.
      The pretreatment of mice with S. caprea flower extract at a dose range of 50-150
      mg/kg of body weight for 7 days followed by FeNTA treatment caused preservation
      of all these parameters. The present study indicates that the flowers of S.
      caprea possess a significant antioxidant and hepatoprotective property, the
      former being implicated in the latter.

PMID- 16619351
TI  - A study of the trypanocidal activity of triterpene acids isolated from Miconia
      species.
AB  - Triterpene acids, including ursolic acid (1), urjinolic acid (4) and oleanoic
      acid (5) along with a mixture of 2alpha-hydroxyursolic acid (2) and maslic acid
      (3) were isolated from methylene chloride extracts of the Miconia sellowiana and
      M. ligustroides species and their activities against the trypomastigote blood
      forms of Trypanosoma cruzi were evaluated. The potassium salt derivative of
      ursolic acid (1a) was also tested. The in vitro assays showed that compounds 1, 5
      and 1a were the most active (IC(50) 17.1 microm, 12.8 microm and 8.9 microm,
      respectively). In contrast, a mixture of 2 plus 3, that exhibit a hydroxyl at C-2
      and C-3, is much less potent than a mixture of 1 and 5 (IC(50) 48.5 microm and
      11.8 microm, respectively). In the same manner, compound 4, that differs from 5
      by two additional hydroxyl groups (at C-2 and C-23) displayed weak trypanocidal
      activity (IC(50) 76.3 microm) when compared with the other triterpenes. These
      results suggest that the free hydroxyl at C-3 and the polarity of C-28 are the
      most influential structural features for determining the in vitro trypanocidal
      activity of triterpenes. In vivo assays were also undertaken for the most active
      compounds 1, 1a and the mixture of 1 plus 5. The most significant reduction in
      parasite number in the parasitemic peak were obtained for compound 1 and its salt
      derivative 1a (75.7% and 70.4%, respectively). Moreover, the survival time was
      increased for all the treated animals.

PMID- 16619352
TI  - St John's wort modulation and developmental expression of multidrug transporters
      in the rat.
AB  - Extracts of St John's wort (SJW) (Hypericum perforatum) are a potent inducer of
      enzymes of the cytochrome P450 system and of the transport protein P
      glycoprotein, and interactions with a range of commonly prescribed medications
      have been described. In addition, recent experimental data suggest that, this
      otherwise safe treatment, could have some side effects when consumed during
      pregnancy and lactation. The aim of this study was to investigate, in Wistar
      rats, the effect of a treatment with high doses of SJW extract (100 and 1000
      mg/kg/day) administered prenatally and during breastfeeding, on the level of
      transcripts of mdr1a, mdr1b, mrp1, mrp2 and cyp3A2 genes. All transcripts were
      detected in the liver, and their level of expression increased from fetuses to
      adults. SJW administration, at both dosages, caused a significant decrease of the
      levels of mdr1a, mdr1b, mrp1 and mrp2 in the livers of fetuses, and an increase
      in the levels of mdr1a, mdr1b, mrp2 and cyp3A2 in the mothers. In the other
      organs examined, a physiological regulation during ontogenesis was also evident,
      but SJW administration did not modify the expression level of the considered
      transcripts. These data suggest that the administration of the extract together
      with drugs that are substrates of transport proteins could be particularly
      hazardous during pregnancy.

PMID- 16619353
TI  - Antioxidant screening of medicinal herbal teas.
AB  - Herbal tea consumption is deeply and widely rooted amongst South-American
      populations. In view of the involvement of oxygen- and nitrogen-reactive species
      in the ethiogenesis of several diseases, the antioxidant properties of some of
      the herbal teas most commonly consumed in the southern regions was assessed in
      vitro. Around one-third of the 13 examined herbs, displayed a substantially
      higher ability to scavenge ABTS(+.) radicals (TEAC assay), and to quench the pro
      oxidant species, hypochlorite (HClO) and peroxynitrite (ONOO(-)). Amongst the
      tested herbs, teas prepared from Haplopappus baylahuen, Rosa moschata and Peumus
      boldus showed the highest TEAC and HClO-quenching activities. These herbs were
      around 5- to 7-fold more potent than the least active herbs. Based on the TEAC
      assay, 150 mL of tea prepared from H. baylahuen, R. moschata and P. boldus would
      be equivalent to around 200 mg of Trolox). Teas from H. baylahuen and P. boldus
      were also found to be particularly potent in quenching HClO. In the ONOO(-)
      assay, H. baylahuen and Buddleia globosa showed the highest activities. The
      results obtained suggest that the regular consumption of teas prepared from some
      of these herbs may be useful potentially to provide the organism with molecules
      capable of protecting the gastrointestinal tract against certain pathologically
      relevant oxidant species.

PMID- 16619354
TI  - Reactive radical scavenging and xanthine oxidase inhibition of proanthocyanidins
      from Carallia brachiata.
AB  - Antioxidant-guided separation of Carallia brachiata bark led to a new A-type
      trimeric proanthocyanidin named carallidin (1), along with mahuannin A (2) and p
      hydroxy benzoic acid (3). The structure of 1 was fully characterized by
      interpretation of spectroscopic data and chemical means. Compounds 1 and 2
      exhibited radical scavenging against DPPH (IC(50) 102 and 182 microm) and
      superoxide radical (IC(50) 1.47 and 9.74 microm). In addition, 1 and 2 also
      inhibited xanthine oxidase with IC(50) values of 12.9 and 16.0 microm.

PMID- 16619355
TI  - Antimicrobial activity of saponins from Medicago sp.: structure-activity
      relationship.
AB  - The antimicrobial activity of saponins from Medicago sativa, M. arborea and M.
      arabica against a selection of medically important yeasts, Gram-positive and 
      negative bacteria was investigated. Structure-activity growth inhibitory effects
      of related prosapogenins and sapogenins are also described. Increasing antibiotic
      activity was observed going from the saponin extracts to the sapogenin samples,
      suggesting that the sugar moiety is not important for the antimicrobial efficacy.
      Activity was especially high against Gram-positive bacteria (Bacillus cereus, B.
      subtilis, Staphylococcus aureus and Enterococcus faecalis) with M. arabica being
      the species showing a broader spectrum of action. Discrete antifungal activity
      was also observed, mainly against Saccharomyces cerevisiae. The observed
      antimicrobial properties of M. sativa and M. arborea were related to the content
      of medicagenic acid, while hederagenin seems to contribute to the bioactivity of
      M. arabica total sapogenins.

PMID- 16619356
TI  - Corydalis yanhusuo rhizoma extract reduces infarct size and improves heart
      function during myocardial ischemia/reperfusion by inhibiting apoptosis in rats.
AB  - The aim of the present investigation was to evaluate the effect of an extract
      from Corydalis yanhusuo W.T., a Chinese herbal medicine, on ischemia/reperfusion
      (I/R) injury and to determine the mechanism(s) involved. In rats, the left
      anterior descending (LAD) coronary artery was occluded for 30 min and then
      reperfused for 6 h. 0.5% carboxymethyl cellulose sodium was used as a vehicle
      (I/R control group) and Corydalis yanhusuo rhizoma extract (I/R + CY 200, 100
      mg/kg groups) were given. Infarct size and hemodynamic parameters were measured.
      Apoptosis was detected quantitatively by the terminal transferase dUTP nick end
      labeling (TUNEL) method and confirmed by DNA laddering on agarose gel. The
      expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins was visualized
      by western blot analysis. In contrast to the I/R control group, administration
      with CY 200 mg/kg resulted in a significant reduction in the infarct size and an
      improvement in heart function as evidenced by higher LVSP and +/-dp/dtmax. TUNEL
      positive cells in the ischemic myocardium were also significantly reduced in the
      I/R + CY 200, 100 mg/kg groups, consistent with little DNA laddering in these two
      groups. Furthermore, greater Bcl-2 and attenuated Bax expression was found in the
      CY treated rats. These results suggest that the protective effect of Corydalis
      yanhusuo on myocardial I/R injury is closely associated with the inhibition of
      myocardial apoptosis through modulation of the Bcl-2 family.

PMID- 16619357
TI  - Prevention of sporogony of Plasmodium vivax in Anopheles albimanus by steroids of
      Solanum nudum Dunal (Solanaceae).
AB  - The sporontocidal activity of three steroids (SN-1, SN-2 and SN-4) from Solanum
      nudum Dunal (Solanaceae) was determined against naturally circulating isolates of
      Plasmodium vivax in Anopheles albimanus. Laboratory-reared Anopheles albimanus
      mosquitoes were infected with P. vivax from gametocytemic blood of volunteers
      resident in Buenaventura, Valle del Cauca (Colombian Pacific Coast) by using an
      artificial membrane feeder. Prior to mosquito feeding, gametocytemic blood was
      centrifuged, plasma was separated, packed blood red cells were washed with RPMI
      1640 and then resuspended in non-immune AB serum, then the steroids were added at
      different doses. On day 7 after infection, the presence and number of oocysts in
      mosquitoes was determined. The steroid SN-2 reduced the infection of mosquitoes
      by 90% and the mean number of oocysts by 60%. These data confirmed that the
      experimental steroid is capable of interrupting the sporogonic development of P.
      vivax in Anopheles albimanus. This experimental steroid has potential for
      transmission blocking in vivax malaria.

PMID- 16619358
TI  - The Ginkgo biloba extract, EGb 761, fails to reduce brain infarct size in rats
      after transient, middle cerebral artery occlusion in conditions of unprevented,
      ischemia-induced fever.
AB  - There is much biochemical evidence, but very few studies in animal models of
      stroke in vivo, to suggest that Ginkgo biloba (EGb 761) may offer neuroprotection
      against regional, ischemic brain damage; additional investigations are needed to
      ensure future clinical trials. This study reports the effects of EGb 761 given
      acutely or chronically before ischemia. Rats were subjected to middle cerebral
      artery occlusion (MCAO) for 2 h and the brain infarct size was assessed 24 h
      later. Dipyrone (100 mg/kg, i.p.) was injected 30 min before ischemia, and 2.5
      and 5.5 h after ischemia, to reduce ischemia-induced fever. EGb 761 (Tebonin) was
      given acutely (200 mg/kg, p.o., 60 min before ischemia) or chronically (100
      mg/kg, p.o., once daily, for 14 days before ischemia). Acute or chronic treatment
      with EGb 761, either alone or in combination with dipyrone, did not reduce the
      infarct size compared with saline alone (p > 0.05). Dipyrone failed to prevent
      ischemia-induced fever during the intra-ischemic period (p > 0.05 vs saline; p <
      0.001 vs sham). In the reperfusion phase, dipyrone reduced fever to normothermic
      levels in the group treated acutely with EGb 761 (p < 0.01 vs saline, p > 0.05 vs
      sham) but not after chronic EGb 761 (p < 0.01 vs sham), indicating possible
      pharmacokinetic interaction. In conclusion, within the context of unprevented,
      ischemia-induced fever, the present results demonstrate that EGb 761 has no
      significant effect on brain infarct size.

PMID- 16619359
TI  - Anti-influenza agents from plants and traditional Chinese medicine.
AB  - Influenza is a serious threat to health in all parts of the world. The control
      and treatment of influenza depends mainly on chemical or biochemical agents and,
      to date, some anti-influenza agents have been isolated from plants as a result of
      chemical and pharmacological studies. These agents include a variety of
      polyphenols, flavonoids, saponins, glucosides and alkaloids. Traditional medicine
      focuses on the use of herbs and traditional Chinese medicine has performed well
      in clinical practice and shows a potential in the therapy of influenza and its
      symptoms. The present paper reviews some constituents and extracts from plants
      and traditional Chinese medicine with anti-influenza activity.

PMID- 16619360
TI  - Clinical evaluation of the Chinese herbal medicine formula STA-1 in the treatment
      of allergic asthma.
AB  - Although some formulae of traditional Chinese medicines (TCM) have been used for
      antiasthma treatment, few of them have had sufficient discussion on their
      efficacy, safety and mechanisms. In this study, the availability of the TCM
      formula STA-1 for the treatment of allergic asthma was investigated by conducting
      a double-blind, placebo-controlled and randomized trial. One hundred and twenty
      patients between the ages of 5 to 20 years with mild-to-moderate asthma were
      included. These patients were treated with either STA-1 or placebo in a dose of
      80 g/kg/day and were administered twice daily for 6 months. The main outcome
      measures were a daily diary record of symptoms, supplementary bronchodilator and
      glucocorticoid treatment, changes of pulmonary function (forced expiratory volume
      in 1 s), changes of total and Dermatophagoides pteronyssinus (DP)-specific IgE
      and side effects. The results showed a statistically significant reduction of
      symptom scores, systemic steroid dose, total IgE and specific IgE in the STA-1
      group. Furthermore, STA-1 also improved the pulmonary lung function FEV(1)
      compared with the placebo group and only minimal side effects were shown. These
      results suggested that STA-1 is available for the treatment of mild-to-moderate
      chronic asthma.

PMID- 16619361
TI  - Evaluation of anxiolytic activity of spray dried powders of two South Brazilian
      Passiflora species.
AB  - The Passiflora extracts have been used in folk medicine because of its reputed
      sedative and anxiolytic properties. The present study aimed to compare the
      potential anxiolytic activity of two Passiflora spray-dried powders obtained from
      P. alata and P. edulis, known in Brazil as 'maracuja'. Male adult Swiss rats were
      treated with 200, 400 and 800 mg/kg of spray-dried powders p.o. and anxiolytic
      activity was evaluated using the elevated plus-maze test. The spray-dried powders
      showed anxiolytic activity in doses of 400 and 800 mg/kg. Our results support the
      potential anxiolytic effect of Passiflora spray-dried powders (P. alata and P.
      edulis).

PMID- 16619362
TI  - Modulatory effects of several herbal extracts on avian peripheral blood cell
      immune responses.
AB  - Standardized ethanol extracts of Allium sativum (garlic), Glycyrrhiza glabra
      (licorice), Plantago major (plantain) and Hippophae rhamnoides (sea buckthorn)
      were assessed for their effects on cellular immunity in laying hens. Birds (n =
      25) had blood samples taken and both specific and non-specific immune cell
      responsiveness were evaluated by a leukocyte proliferation assay, carbon
      clearance test and SRBC phagocytosis in monocyte-derived macrophage cultures.
      Licorice and sea buckthorn (50 microg/mL) clearly enhanced the macrophage
      membrane function (p < 0.05 and p < 0.01, respectively). Dual effects on
      circulating phagocytes were revealed for plantain and sea buckthorn, while garlic
      at 200 microg/mL impaired the phagocytic capacity of blood cells. None of the
      tested extracts showed mitogenic properties, but high concentrations of sea
      buckthorn (400 microg/mL) inhibited leukocyte proliferation. Small concentrations
      (20 microg/mL) of licorice proved the co-mitogenic potential for both T and B
      avian lymphocytes (p < 0.05). Certain extracts definitely enhanced the fowl
      innate and/or specific cell immunity and may therefore improve host resistance in
      poultry. Considering the chicken as an important non-mammalian model that also
      serves as an available laboratory approach for some human diseases, herbs
      exerting immunomodulatory properties may find relevant clinical applications.

PMID- 16619363
TI  - Protective effects of sugar cane extract on endotoxic shock in mice.
AB  - Sugar cane extract (SCE) has been shown to have an immunostimulating effect in
      chickens. This study evaluated the effect of SCE on Salmonella Abortusequi
      lipopolysaccharide (LPS)-induced lethal shock in d-galactosamine (GalN)
      sensitized mice. Mice were administered intraperitoneally SCE (500 mg/kg) or
      phosphate buffered saline before or after injection of LPS and GalN. All the mice
      injected with LPS and GalN (control group) died of histopathologically congestive
      and hemorrhagic hepatic insufficiency within 24 h, showing significantly
      increased activities of plasma aspartate aminotransferase (AST; 380 IU/mL) and
      alanine aminotransferase (ALT; 130 IU/mL). Pretreatment of mice with SCE at 3 h
      before challenge with LPS and GalN (SCE treated group) resulted in significantly
      improved survival rates (92.3%) and a decrease in liver injury. These surviving
      mice in the SCE treated group showed no changes in the mean levels of plasma AST
      (60 IU/mL) and ALT (18 IU/mL). However, the level of tumor necrosis factor-alpha
      in the SCE treated group was not significantly different when compared with that
      in the control group challenged with LPS and GalN. These results suggest that SCE
      has protective effects on LPS-induced mortality in this mouse model.

PMID- 16619364
TI  - Potential anti-inflammatory effects of Melaleuca alternifolia essential oil on
      human peripheral blood leukocytes.
AB  - The fungicidal and bactericidal actions of the essential oil (EO) of Melaleuca
      alternifolia seem well established, but their anti-inflammatory and antioxidative
      effects remain unclear. This study investigated in vitro the possible role of
      whole Melaleuca alternifolia EO as a modulator of the inflammatory/non-specific
      immune response by exploring the chemotaxis and kinetic radical oxygen species
      (ROS) production of leukocytes and cytokine secretion in peripheral blood
      mononuclear cells (PBMCs) in humans. The influence of Melaleuca alternifolia EO
      on the chemotaxis under agarose of isolated neutrophils (PMNs) was evaluated. The
      kinetics of ROS production by stimulated total circulating leukocytes was
      followed over 2 h by recording the fluorescence intensity of oxidized
      dihydrorhodamine 123. The effects of this EO on pro-(interleukin IL-2) and anti
      (IL-4 and IL10) inflammatory cytokine secretions were determined by ELISA
      following incubation of PBMCs with the EO for 24 h. Melaleuca alternifolia EO was
      inefficient on the chemotaxis of PMNs. It exerted an antioxidant effect, reducing
      ROS production throughout the kinetic study. Melaleuca alternifolia EO inhibited
      PBMC proliferation, as revealed by a reduction in IL-2 secretion by stimulated
      lymphocytes. This EO at 0.1% directly increased the secretion of the anti
      inflammatory cytokine IL-4 compared with IL-4 secretion without EO (18.5 +/- 10.0
      vs 3.3 +/- 1, p < 0.05), and also increased IL-10 secretion at 0.01% (94.9 +/-
      38.7 vs 44.1 +/- 18, ns). Melaleuca alternifolia EO may not only act as an anti
      inflammatory mediator through its antioxidant activity but may also efficiently
      protect the organism by reducing the proliferation of inflammatory cells without
      affecting their capacity to secrete anti-inflammatory cytokines.

PMID- 16619365
TI  - Composition and antibacterial activity of Abies balsamea essential oil.
AB  - The antibacterial activity of the essential oil of Abies balsamea (balsam fir)
      was evaluated against Escherichia coli and Staphylococcus aureus. The essential
      oil of A. balsamea was found to be inactive against E. coli (>100 microg/mL) and
      active against S. aureus, with an MIC of 56 microg/mL. The oil composition was
      analysed by GC-MS and the antibacterial activity of each oil constituent was
      determined. The essential oil of A. balsamea is essentially constituted of
      monoterpenes (>96%) and some sesquiterpenes. beta-pinene (29.9%), delta-3-carene
      (19.6%) and alpha-pinene (14.6%) were the major components. beta-pinene and delta
      3-carene were found inactive against both bacteria strains. However, three
      constituents of the essential oil were active against S. aureus: alpha-pinene,
      beta-caryophyllene (0.4%) and alpha-humulene (0.2%) with MIC values of 13.6
      microg/mL, 5.1 microg/mL and 2.6 microg/mL, respectively.

PMID- 16619366
TI  - Neurophysiological effects of mistletoe (Viscum album L.) on isolated rat
      intestines.
AB  - Mistletoe (Viscum album L.) is well known as a medicine from ancient times and
      the earliest notes. Today it is used as a remedy. The aim of this research was to
      examine the effects of mistletoe extracts and their components on some
      neurophysiological parameters in rat intestines. The tonus and contractile
      responses of isolated intestinal segments (duodenum, ileum and distal colon) were
      analysed. The experiment was carried out in three groups. In the first group
      (control group) different concentrations of acetylcholine were added into the
      organ bath (10-50 nmol/L). In the second group, mistletoe extracts were added
      into the organ bath with increasing concentrations and in the third group,
      atropine, a non-selective muscarinic receptor antagonist, was added into the
      organ bath (concentration 10(-7) mol/L) and after atropine plant extracts were
      administered. The results obtained suggest that extracts from different parts of
      mistletoe have neurophysiological effects and change intestinal contractions. The
      results also suggest that the effects of mistletoe extracts on intestinal
      contractility act via cholinergic pathways, activating muscarinic receptors in
      the intestines. However, in order to establish the subtype of receptors, further
      investigations are necessary where selective antagonists of muscarinic
      cholinergic receptors should be used.

PMID- 16619367
TI  - Plants and animals utilized as medicines in the Jau National Park (JNP),
      Brazilian Amazon.
AB  - This article examines the therapeutic practices of the inhabitants of Jau
      National Park (JNP), state of Amazonas, the most important feature of this region
      being its rich biodiversity associated with isolation in regard to conventional
      medical services. Seven months of field work were guided by methods of
      anthropology and botany. A total of 120 plants and 29 animals were utilized in
      519 recorded uses comprising 81 therapeutic purposes. These were grouped under 15
      categories of use, including: gastrointestinal disturbances, inflammatory
      processes, genitourinary disturbances, fever, mishaps with animals,
      dermatological problems, pain, osteomuscular problems and tropical diseases.
      Those who administer these medicines are local residents specializing in
      household remedies and other groups of healers such as rezadores - prayer-maker;
      curadores - healers; parteiras - midwives; desmintidores - masseurs and mediuns -
      mediums. At least 10 of the 120 plants species cited in this study are also
      utilized by other inhabitants of the Amazon region and for the same uses; some of
      these plants had already been studied from a pharmacological point of view.
      Furthermore, another six plants cited by the JNP caboclos belonging to the
      categories pain and inflammatory processes, are under investigation by groups of
      researchers in two Brazilian federal universities.

PMID- 16619368
TI  - In Vivo radioprotective effect of Panax ginseng C.A. Meyer and identification of
      active ginsenosides.
AB  - This study evaluated the effect of water extracts of Panax ginseng C.A. Meyer
      (PG), panaxadiol (PD), panaxatriol (PT), ginsenoside Rb(1), Rb(2), Rc, Rd, Re and
      Rg(1) on jejunal crypt survival, endogenous spleen colony formation and apoptosis
      in jejunal crypt cells in gamma-irradiated mice. Jejunal crypts were protected by
      pretreatment with PG, Rc and Rd. Administration of PG, PD, Rd and Re prior to
      irradiation resulted in an increase in the formation of endogenous spleen
      colonies. The frequency of radiation-induced apoptosis in intestinal crypt cells
      was also reduced by pretreatment with PG, PD, Rb(2), Rc, Rd, Re and Rg(1). In
      experiments on the effects of the individual ginsenosides, the rank order of
      activity was Rc > Rd > Rg(1) > Rb(2) > Re > Rb(1) on intestinal crypt survival
      assay, Re > Rb(2) > Rd > Rg(1) > Rb(1) > Rc on the spleen colony formation assay,
      and Rg(1) > Re > Rd > Rc > Rb(2) > Rb(1) on inhibiting the death of cells caused
      by apoptosis. The results indicated that Rc, Rd and Re may have a major
      radioprotective effect in mice irradiated with high and low doses of radiation.
      When the same experiments were performed using PD and PT, it was observed that
      most of the inhibitory effects came from PD rather than PT.

PMID- 16619369
TI  - Effects of mycelial culture of Phellinus linteus on ethanol-induced gastric ulcer
      in rats.
AB  - The gastroprotective effects of a mycelial culture of Phellinus linteus (MCPL)
      were evaluated by determining the ulcer index, gastric mucus content,
      histopathological observation and histochemical properties of mucin in an ethanol
      induced ulcer model of rats. Preadministration with MCPL at doses of 20 and 60
      mg/kg, showed a significant decrease of bleeding and ulcer index and alleviated
      the histopathological changes induced by ethanol such as hemorrhage and necrosis.
      Ethanol treatment decreased the gastric adhesion mucus content, but a higher
      level of gastric mucus persisted after preadministration of MCPL. As for the
      histochemical properties of mucins, marked changes were observed in both the
      surface and gland mucous cells in ethanol-treated rats, but these changes were
      detected only in the surface mucous cells in rat preadministered with MCPL. Using
      conventional methods for mucins, ethanol-treated rats revealed a decrease of
      neutral and acid mucin in the surface epithelium and mucous neck cells compared
      with normal rats. A marked decrease of BSL-1 by lectin histochemistry was also
      revealed in the ethanol-treated rats. But the MCPL preadministered rats showed
      similar stainabilities and lectin affinity patterns for mucins as the normal
      rats. These results indicate that pretreatment with MCPL provided protection of
      the gastric mucosa from ethanol-induced injury by maintaining the mucus barrier
      in rats.

PMID- 16619370
TI  - Effect of lemnan, pectin from Lemna minor L., and its fragments on inflammatory
      reaction.
AB  - An effect of apiogalacturonanic pectin of duckweed Lemna minor L. (lemnan LM) was
      studied on the inflammatory response to ovalbumin injected intradermally into the
      footpad of control and ovalbumin-fed mice. Lemnan LM (1-2 mg per mouse) was found
      to enhance by as much as 50-60% the footpad swelling in control mice. Oral
      administration of ovalbumin was shown to result in sensitization that increased
      inflammation. Ovalbumin admixed with lemnan was found to increase by two-fold
      footpad edema in comparison with the mice receiving ovalbumin alone. Apple pectin
      used as a reference compound failed to influence the inflammatory reaction.
      Degradation of lemnan was performed to elucidate the active region of the
      polysaccharide macromolecule. The apiogalacturonanic fragment (LMP) obtained
      using a digestion of lemnan LM with pectinase was shown to increase the footpad
      response in both control and ovalbumin-fed mice. Fragment LMPH deprived of some
      terminal apiose residues as a result of partial acidic hydrolysis failed to have
      an effect on the inflammatory response.Thus, the data obtained reveal an
      enhancement by lemnan of the inflammatory response. The ramified apiogalacturonan
      seemed to be the active region of the lemnan macromolecule.

PMID- 16619371
TI  - Role of oil extract of garlic (Allium sativum Linn.) on intestinal transference
      of calcium and its possible correlation with preservation of skeletal health in
      an ovariectomized rat model of osteoporosis.
AB  - The present study was undertaken to examine the effects of an oil extract of
      garlic on the in vivo intestinal transference of calcium, and also to verify its
      role in maintaining the bone mineral content and bone tensile strength in an
      ovariectomized rat model of osteoporosis. The results suggest that, in this
      experimental model, oil extract of garlic promotes intestinal transference of
      calcium by modulating the activities of both intestinal alkaline phosphatase and
      Ca(2+) activated ATPase. Also the observed low bone mineral content and low bone
      tensile strength in these rats were significantly restored by garlic oil
      supplementation. Further, garlic oil supplementation was able to revive partially
      the bilateral ovariectomy-induced decrease in the serum estrogen titer. The serum
      parathyroid hormone level, however, was found unaltered in these rats. The garlic
      oil supplemented partial recovery in serum estrogen titer in bilaterally
      ovariectomized rat was found to be persistently associated with enhanced calcium
      transference and better preservation of bone mineral content. The results of this
      study propose that the phytoestrogenic efficacy of an oil extract of garlic
      prevents ovarian hormone deficiency induced bone mineral loss possibly by
      promoting intestinal transference of calcium through the partial revival of the
      serum estrogen titer.

PMID- 16619372
TI  - Antienterobacterial activity of Hemidesmus indicus R. Br. root extract.
AB  - The antienterobacterial activity of the chloroform and methanol extracts of
      Hemidesmus indicus root was demonstrated using a variety of methods and different
      enterobacterial strains. Although the constituents were similar in the chloroform
      extract (CHI) and the fatty substance separated (ME1) from the methanol extract
      (MHI), ME1 was found to be more effective than CHI as evident from the disc
      diffusion method. ME1 was found to be more active than MHI, followed by CHI. This
      may be due to the inefficient diffusion of CHI into the medium. In a modified
      agar well diffusion and swab method the activity of the extract against different
      strains was observed in a single plate. The extracts inhibited growth in a dose
      dependent manner; both MHI and CHI were most effective against S. flexneri, least
      effective against S. dysenterie and moderately effective against the other
      strains. The presence of antimicrobial trace elements such as copper and zinc,
      along with other active constituents may contribute to the antienterobacterial
      activity of Hemidesmus indicus root.

PMID- 16619373
TI  - Fatty acids profile and antiinflammatory activity of Nonea setosa R. et S.
AB  - In order to verify the antiinflammatory properties of Nonea setosa R. et S. (Fam.
      Boraginaceae) and to identify the relevant active principles, aerial parts of
      this plant were extracted with increasing polarity solvents. The antiinflammatory
      activity was investigated by a bioassay-oriented fractionation using the
      inhibition of the croton oil-induced ear oedema in mice as an experimental model
      of inflammation. GC-MS analysis of the most active fraction revealed the presence
      of high amounts of polyunsaturated fatty acids.

PMID- 16619374
TI  - Effect of a combination of extract from several plants on cell-mediated and
      humoral immunity of patients with advanced ovarian cancer.
AB  - The influence of a plant preparation AdMax (Nulab Inc., Clearwater, FL, USA) on
      immunity in ovarian cancer patients was studied. The preparation is a combination
      of dried ethanol/water extracts from roots of Leuzea carthamoides, Rhodiola
      rosea, Eleutherococcus senticosus and fruits of Schizandra chinensis. Twenty
      eight patients with stage III-IV epithelial ovarian cancer were treated once with
      75 mg/m(2) cisplatin and 600 mg/m(2) cyclophosphamide. Peripheral blood was
      collected 4 weeks after the chemotherapy. Subclasses of T, B and NK lymphocytes
      were tested for in the blood samples: CD3, CD4, CD5, CD7, CD8, CD11B, CD16, CD20,
      CD25, CD38, CD45RA, CD50, CD71 and CD95. Immunoglobulin G, A and M concentrations
      were also determined. Changes were observed in the following T cell subclasses:
      CD3, CD4, CD5 and CD8. In patients who took AdMax (270 mg a day) for 4 weeks
      following the chemotherapy, the mean numbers of the four T cell subclasses were
      increased in comparison with the mean numbers of the T cell subclasses in
      patients who did not take AdMax. In patients who took AdMax, the mean amounts of
      IgG and IgM were also increased. The obtained results suggest that the
      combination of extracts from adaptogenic plants may boost the suppressed immunity
      in ovarian cancer patients who are subject to chemotherapy.

PMID- 16619375
TI  - Posterior fossa and vermian morphometry in the characterization of fetal
      cerebellar abnormalities: a prospective three-dimensional ultrasound study.
AB  - OBJECTIVES: To assess whether, by applying a predefined set of morphometric
      measurements to the posterior fossa and the cerebellar vermis, it is possible to
      detect and quantify the following parameters, which represent key features of
      abnormalities of the vermis and posterior fossa: 1) upward rotation of the
      vermis; 2) upward displacement of the tentorium; 3) underdevelopment of the
      vermis. Also to assess, in a small subset of cases, the correlation between
      ultrasound and magnetic resonance imaging (MRI) in the measurement of these three
      parameters. METHODS: This was a prospective observational trial. The study
      population included 51 normal fetuses and 20 abnormal fetuses with Dandy-Walker
      malformation (n = 5), Dandy-Walker variant (n = 8) or megacisterna magna (n = 7).
      Three-dimensional (3D) ultrasound volumes of the fetal head were acquired from
      the posterior fontanelle or the posterior part of the sagittal suture and
      processed offline with dedicated software. The following parameters were
      analyzed: tentorovermian angle; tentoroclivus angle; clivovermian angle; vermian
      diameter/biparietal diameter x 100 ratio (VD/BPD ratio). In seven cases, MRI
      performed on the same day as sonography was available for comparison. Non
      parametric statistics were used to assess differences in means and correlations.
      RESULTS: The tentoroclivus angle was increased only in fetuses with Dandy-Walker
      malformation (P < 0.001). Upward rotation of the vermis was demonstrated both by
      the tentorovermian and the clivovermian angles in fetuses with Dandy-Walker
      variant (P < 0.001), while in those with Dandy-Walker malformation the difference
      was not statistically significant, probably due to the small number of cases.
      Finally, the VD/BPD ratio demonstrated that the degree of vermian hypoplasia was
      higher in Dandy-Walker malformation compared with Dandy-Walker variant (P <
      0.001). CONCLUSIONS: Using 3D ultrasound, we have demonstrated in the fetus the
      key elements characterizing most anomalies of the posterior fossa, namely the
      upward displacement of the tentorium, the counterclockwise rotation and the
      significant hypoplasia of the cerebellar vermis. In addition, our observations in
      a small number of cases indicate that there is a good correlation between MRI-
      and 3D ultrasound-derived morphometric measurements of the vermis.

PMID- 16619376
TI  - The role of spatio-temporal image correlation (STIC) with tomographic ultrasound
      imaging (TUI) in the sequential analysis of fetal congenital heart disease.
AB  - OBJECTIVE: Spatio-temporal image correlation associated with the tomographic
      ultrasound imaging mode (TUI-STIC) is a new modality that allows a complete
      sequential analysis of cardiac structures to be displayed on a single panel by
      showing all echocardiographic transverse views at the same time. The aims of this
      study were to identify the best settings for displaying the classic
      echocardiographic views at different gestational ages and to investigate the role
      of TUI-STIC in the sequential segmental analysis of complex congenital heart
      disease (CHD). METHODS: Four-dimensional volumes from 103 cases of confirmed
      fetal CHD diagnosed and managed at our referral center were evaluated using TUI
      STIC. To select the best interslice distance for adequate display of the central
      cardiovascular connections, each volume was opened and the TUI mode activated,
      having as a reference the apical four-chamber view. The number of slices was set
      at nine. The volume was then scrolled until the most significant
      echocardiographic views were displayed on the screen windows. Then, if too many
      windows showed intermediate non-diagnostic views, the slice distance was adjusted
      finely until all key echocardiographic views showed up in the various windows.
      The interslice distance was regressed against gestational age and the best
      fitting curve was identified. RESULTS: A sequential segmental analysis could be
      shown with TUI-STIC in all cases. A linear regression equation best fitted the
      correlation between interslice distance and advancing gestational age (r(2) =
      0.9042), with the mean interslice distance being 2.7 (SD, 0.3) mm at 19-23
      gestational weeks, and 4.0 (SD, 0.4) mm at 30-33 weeks. These settings allowed a
      complete sequential analysis in all cases. CONCLUSIONS: TUI-STIC allows a
      complete sequential analysis of CHD in the fetus. The most suitable interslice
      distances for all gestational ages could be identified. These data may be used
      while adopting this imaging modality in the four-dimensional evaluation of fetal
      CHD.

PMID- 16619378
TI  - Postmortem magnetic resonance imaging as an adjunct to the diagnosis of skeletal
      dysplasias: short-rib polydactyly syndrome.

PMID- 16619377
TI  - Antenatal ultrasound and magnetic resonance imaging in localizing the level of
      lesion in spina bifida and correlation with postnatal outcome.
AB  - OBJECTIVE: To compare prenatal ultrasonography and magnetic resonance imaging
      (MRI) in the diagnosis of spina bifida with postnatal MRI/surgical findings and
      to study the postnatal outcome in relation to the level of lesion and head signs
      on antenatal imaging. METHODS: A retrospective study of babies referred to a
      tertiary neurosurgical unit with a diagnosis of spina bifida in the years 2000
      2002 was performed. The levels of lesions and head signs diagnosed using
      antenatal ultrasonography and MRI were compared with postnatal MRI and operative
      findings. The levels of lesions and head signs diagnosed pre- and postnatally
      were used to study the correlation with neurological outcome at a mean follow-up
      period of 12 months. RESULTS: Twelve antenatally diagnosed and five postnatally
      diagnosed cases of spina bifida were seen. The level of lesion as identified by
      antenatal ultrasound correlated with that observed postnatally in 8/12 cases and
      the antenatal ultrasound diagnosis of ventriculomegaly was confirmed postnatally
      in all cases. The level of lesion as identified by antenatal MRI correlated with
      that observed postnatally in 4/8 cases (50%) and the antenatal MRI diagnosis of
      ventriculomegaly was confirmed postnatally in 5/8 (63%) cases. 12/17 babies were
      found to have residuals in the immediate postnatal urodynamic studies, of which
      83% (n = 10) required intermittent catheterization of the bladder at 12 months of
      age. Low spinal lesions were associated with increased bladder morbidity when
      compared to high spinal lesions (8/10 vs. 4/7, P < 0.05) (odds ratio (OR) = 10.0;
      95% CI, 1.05-95.01). The level of spinal lesion and the presence of
      ventriculomegaly did not have any statistically significant correlation with
      motor functions, morbidity and developmental milestones. CONCLUSIONS: Antenatal
      ultrasonography is a good tool in the diagnosis of spina bifida. We could not
      demonstrate any advantage of antenatal MRI over ultrasonography. There is better
      correlation of ultrasonography than MRI with postnatal MRI/operative findings in
      terms of level of lesion and head signs. Low spinal lesions appear to be
      associated with increased bladder morbidity.

PMID- 16619379
TI  - Steatotic hepatocellular carcinomatosis mimicking malignant ovarian teratoma.

PMID- 16619380
TI  - Sonographic developmental milestones of the fetal cerebral cortex: a longitudinal
      study.
AB  - OBJECTIVE: To identify sonographic landmarks of normal fetal cortical
      development. METHODS: Serial ultrasound examinations were performed every 2 weeks
      from 18 weeks of gestation until term. In each session a detailed examination of
      the fetal brain was performed and the appearance of the main sulci and gyri was
      recorded. RESULTS: Twenty-two pregnant women volunteered to participate in the
      study. The fetal cortex followed an orderly pattern of development. By the time
      of the first ultrasound examination, at 18 weeks, the major fissures were
      present. The first sulci could be demonstrated as early as 18 weeks. Main
      landmarks, represented by the parieto-occipital fissure and the cingulate and
      calcarine sulci, were present between 22-24 weeks. The central sulcus was present
      in all cases by 28 weeks. By 30-32 weeks most of the main sulci could be
      demonstrated. CONCLUSIONS: Prenatal sonographic examinations can accurately
      demonstrate structures of the fetal cortex. Comparison of our results with those
      of both magnetic resonance imaging and other sonographic studies shows
      similarities in the order of appearance of the sulci and gyri, with only minor
      differences in the exact gestational age at which they are detected. Accurate
      knowledge of the ultrasound appearance of the fetal cortex at different stages of
      gestation is important in order to be able to diagnose in-utero malformations of
      cortical development.

PMID- 16619381
TI  - Rotation of the vermis as a cause of enlarged cisterna magna on prenatal imaging.
AB  - OBJECTIVES: Dandy-Walker complex is a continuum of developmental anomalies of the
      posterior fossa which includes vermian rotation. However, vermian rotation alone
      may be benign. The aim of this study was to describe our experience with sagittal
      plane prenatal ultrasound in the diagnosis of rotation of the vermis in cases of
      suspected enlarged cisterna magna on routine antenatal imaging, and to describe
      the follow-up of these patients. METHODS: Seven women, who were referred to our
      ultrasound unit for evaluation of an enlarged fetal cisterna magna and suspected
      agenesis of the vermis on axial-plane imaging, underwent further multiplanar
      studies of the posterior fossa and measurements of the vermis. RESULTS: The mean
      maternal age was 27 (range, 20-33) years and the mean gestational age at
      diagnosis was 19.5 (range, 18-31) weeks. The standard axial plane image showed a
      'direct communication' between the cisterna magna and the fourth ventricle. In
      the mid-sagittal plane, the vermis was clearly delineated, with posterosuperior
      rotation. Vermis size was within normal limits for gestational age in all cases.
      Findings were confirmed by prenatal magnetic resonance imaging (MRI) in two cases
      and postnatal MRI and/or sonography in five. During a mean follow-up of 4.5
      (range, 1-7.5) years, all children developed normally, with no neurological
      complications. CONCLUSION: The finding of an enlarged cisterna magna on standard-
      (axial-)plane ultrasound should be evaluated further in the sagittal plane to
      determine whether the cause is rotation of a normal vermis. This may spare
      patients unnecessary tests, anxiety and, in some cases, pregnancy termination.

PMID- 16619382
TI  - Three-dimensional ultrasound findings of spondylocostal dysostosis in the second
      trimester of pregnancy.
AB  - Spondylocostal dysostosis (SCD) is a rare congenital disorder that is
      characterized by vertebral segmentation and formation defects, and asymmetrical
      rib anomalies. We describe a case diagnosed during the second trimester of
      pregnancy with the sonographic features of abnormal alignment of the spine,
      hemivertebrae in the thoracic spine and kyphoscoliosis. Three-dimensional
      ultrasound demonstrated a 'fan-like' rib cage with fusion of the ribs. The
      postmortem findings confirmed the ultrasound findings and were consistent with
      SCD.

PMID- 16619383
TI  - Three-dimensional ultrasound in the prenatal diagnosis of cleidocranial dysplasia
      associated with B-cell immunodeficiency.
AB  - A patient with a singleton pregnancy was referred for three-dimensional
      ultrasonography (3DUS) at 18 + 3 weeks for suspected hypomineralization of the
      skull bones and absence of the nasal bones. Three-dimensional rendered images of
      the fetal skull revealed widening of the coronal sutures, absence of the squamous
      portion of the temporal bone, and absence of the occipital bone, except for two
      areas of ossification. In addition, a fractured right clavicle was identified.
      The remainder of the fetal anatomy was normal and biometry was appropriate for
      gestational age. Genetic amniocentesis revealed a 46,XX fetal karyotype. Family
      history was positive for a 5-year-old sibling with an open anterior fontanelle.
      Cleidocranial dysplasia was suspected. A female neonate was delivered by elective
      repeat Cesarean section at 40 + 3 weeks of gestation without complications and
      discharged home 3 days after delivery. Prenatal diagnosis was confirmed by
      physical and radiological evaluation. The infant died at 8 weeks of age due to
      respiratory syncytial virus pneumonia secondary to B-cell deficiency. RUNX2
      mutations were not detected by molecular analysis. There are three relevant
      aspects to this case: (1) clear visualization of the widened fontanelles and
      hypomineralized occipital bones was possible with the use of 3DUS; (2) a
      clavicular fracture was identified in utero with combined high-resolution two
      dimensional and 3DUS; and (3) although absence of the nasal bones is most
      commonly observed in fetuses with chromosomal disorders (e.g. trisomy 21 and
      trisomy 18), a careful examination of the skeleton should be considered in
      fetuses with absent nasal bones and a normal karyotype.

PMID- 16619384
TI  - Plea for an anatomical approach to abnormalities of the posterior fossa in
      prenatal diagnosis.

PMID- 16619385
TI  - Cleft of the secondary palate without cleft lip diagnosed with three-dimensional
      ultrasound and magnetic resonance imaging in a fetus with Fryns' syndrome.
AB  - We present a case of Fryns' syndrome diagnosed prenatally using three-dimensional
      (3D) ultrasonography and magnetic resonance imaging (MRI). A cleft of the soft
      palate was diagnosed using 3D thick-slice ultrasonography. Other sonographic
      findings included a right diaphragmatic hernia, enlarged echogenic kidneys and
      severe polyhydramnios. The detection of the cleft palate was instrumental in
      suggesting the diagnosis of Fryns' syndrome in a fetus which also had a
      diaphragmatic hernia. These findings were also demonstrated with prenatal MRI.
      The technique of imaging the soft palate en face using a thick-slice technique is
      presented.

PMID- 16619386
TI  - Fetal brain volume measurements by magnetic resonance imaging.

PMID- 16619387
TI  - Characteristics, associations and outcome of partial agenesis of the corpus
      callosum in the fetus.
AB  - OBJECTIVES: To report, in a population of fetuses diagnosed with partial agenesis
      of the corpus callosum (PACC), the sonographic characterization, incidence of
      cerebral, extracerebral and chromosomal anomalies, and outcome. In addition, in
      some of our cases a comparison was made between findings on ultrasound and fetal
      magnetic resonance imaging (MRI). METHODS: This was a retrospective study of all
      cases of PACC seen at two referral centers for prenatal diagnosis of congenital
      anomalies over a 10-year period. The following variables were assessed:
      indication for referral, additional cerebral and extracerebral malformations,
      chromosomal abnormalities, and pregnancy and fetal/neonatal outcome. RESULTS:
      Among 54 cases of fetal agenesis of the corpus callosum detected in the referral
      centers during the observation period, PACC was diagnosed at prenatal sonography
      in 20 cases and confirmed at pre/postnatal MRI and necropsy examinations in 19
      cases (35%). These 19 constituted the study group. The diagnosis was made in the
      sagittal planes and in 12 cases it was made prior to 24 weeks. In most cases the
      indication for referral was the presence of indirect signs of callosal anomalies,
      such as colpocephaly. In 10 cases PACC occurred in association with other
      anomalies and in nine it was isolated. MRI was particularly useful for
      demonstrating some additional cerebral anomalies such as late sulcation,
      migrational pathological conditions and heterotopia. Regarding pregnancy outcome,
      of those diagnosed before 24 weeks which had associated anomalies, all except two
      were terminated. Of the nine cases with isolated PACC, all were liveborn. Follow
      up was available in eight, and two of these (25%) showed evidence of significant
      developmental delay. In our series the outcome of isolated PACC was not better
      than that of complete agenesis of the corpus callosum reported in other series.
      CONCLUSIONS: PACC can be diagnosed reliably and characterized in prenatal life.
      The sonographic sign present in most cases is colpocephaly. Prenatal MRI can be
      performed to confirm the diagnosis. It is particularly useful to demonstrate some
      additional cerebral anomalies such as late sulcation, migrational pathological
      conditions and heterotopia. The relatively poor survival rate is due to the high
      rate of terminations and associated major anomalies.

PMID- 16619388
TI  - Fetal magnetic resonance imaging: luxury or necessity?

PMID- 16619389
TI  - The long road to equality.

PMID- 16619390
TI  - Breaking into business.

PMID- 16619391
TI  - A meeting of biomedical minds.

PMID- 16619392
TI  - Tobias' dual role heightens concern over US humanitarian aid.

PMID- 16619393
TI  - Canadian researchers respond to CMAJ crisis.

PMID- 16619395
TI  - Readers' responses to "doctors and patients working together".

PMID- 16619394
TI  - Visceral hypersensitivity in irritable bowel syndrome: a summary review.
AB  - We examined published reports from 1970 to the present to evaluate the theory
      that abnormal visceral sensitivity characterizes the irritable bowel syndrome.
      Evidence to support claims that abnormal visceral sensitivity defines the
      irritable bowel syndrome falls short because of cognitive deficits in
      gastrointestinal neurobiology, limitations in experimental design and execution,
      and the interpretation of results.

PMID- 16619396
TI  - Environmental impact of the U.S. nuclear submarine base at La Maddalena
      Archipelago, Sardinia, Italy.

PMID- 16619397
TI  - Results of measurements carried out on samples collected around the Maddalena
      Island, Sardinia, Italy.

PMID- 16619398
TI  - ER patients insured: study. Data reveal misperceptions about emergency rooms.

PMID- 16619399
TI  - Ruling spreads confusion. Guidant's victory could stop sharing of price data.

PMID- 16619400
TI  - Ahead of the pack. 10% of Mich. hospitals have already adopted CPOE.

PMID- 16619401
TI  - ACHE Gold Medal Award. Making a difference. Sanders found his way to healthcare
      via a mentor.

PMID- 16619402
TI  - ACHE Honorary Fellow. Taking on AIDS. Tobias cites need to improve global
      infrastructure.

PMID- 16619403
TI  - Stigma attached to mental illness.

PMID- 16619404
TI  - Crossed wires.

PMID- 16619406
TI  - Never let it be said that this column is always full of gloom and doom.

PMID- 16619405
TI  - Working well.

PMID- 16619407
TI  - Electroacupuncture in the treatment of a ganglion of the wrist--a case report.
AB  - A ganglion is a cystic swelling that occurs most commonly in women. Recurrence is
      possible after conservative or surgical treatment. A novel method of therapy,
      electroacupuncture stimulation, was performed in a 53 year old woman with a
      large, recurrent dorsal wrist ganglion. After treatment it rapidly disappeared
      and there was no recurrence during the one year follow-up period. Although the
      mechanism is obscure, it is our impression that electroacupuncture may have a
      local action on such cysts in addition to needle drainage.

PMID- 16619408
TI  - Continued use of trastuzumab (herceptin) after progression on prior trastuzumab
      therapy in HER-2-positive metastatic breast cancer.
AB  - Whether to continue trastuzumab after objective evidence of disease progression
      or not is an important unanswered clinical question for women with metastatic
      disease. This question is also relevant for those who relapse after adjuvant
      trastuzumab-containing therapy. Unfortunately, there is little evidence to guide
      decision-making. The modest toxicity and the possible, but unproven, benefit from
      the continued use of trastuzumab may account for the currently wide spread
      practice of continued administration of this drug after progression. However,
      there is no convincing evidence to support the use of extended trastuzumab
      therapy after progression. At least two randomized trials with no trastuzumab in
      the control arms were attempted but failed to accrue patients. In the absence of
      results from a randomized clinical trial, a central registry program that
      collects information longitudinally from a large number of patients with HER-2
      positive breast cancer during the course of their disease was initiated
      (RegistHER, www.registher.com) to learn about the long term side effects and
      benefits of prolonged trastuzumab therapy. The anticipated introduction of second
      generation HER2-targeted agents into the clinic also raises a new question; will
      switching to these agents be more effective than continuation of trastuzumab?
      Clinical trials are currently planned to address question prospectively.

PMID- 16619409
TI  - Reasonable accommodations for individuals regarded as having disabilities under
      the Americans with Disabilities Act? Why "No" should not be the answer.

PMID- 16619410
TI  - Mental health courts: no longer experimental.

PMID- 16619411
TI  - No child left without a brain scan? Toward a pediatric neuroethics.
AB  - Brain research is yielding new information about the development of cognitive and
      behavioral traits in children--and how development can go off track. This is
      information parents, teachers, and others will use to help with problems from
      dyslexia to drug abuse. But with this information, often technical, come many
      questions. Will knowledge from brain scans be used to label children early in
      life? How will confidentiality be maintained as diverse providers, some of them
      commercial, compete for patients? Should government pay for scanning all children
      to identify not only potential problems but also extraordinary potential? These
      are questions about values and mutual responsibilities in neuroscience--the
      domain of neuroethics. The authors consider what an ethical framework for
      applying the fruits of neuroscience to children--a pediatric neuroethics--might
      look like.

PMID- 16619412
TI  - Our new Promethean gift.

PMID- 16619413
TI  - Brain science and the self.

PMID- 16619414
TI  - Brain science and social policy.

PMID- 16619415
TI  - No brainer--can we cope with the ethical ramifications of new knowledge of the
      human brain?

PMID- 16619417
TI  - Are there things we'd rather not know?

PMID- 16619416
TI  - Ethics and the practice of brain science.

PMID- 16619418
TI  - Brain science and public discourse.

PMID- 16619419
TI  - What it means to "map" the field of neuroethics.

PMID- 16619421
TI  - Ethical treatment of animals.

PMID- 16619420
TI  - Mapping the future.

PMID- 16619422
TI  - The economics of abortion access in the US: restrictions on government funding
      for abortion is the post-Roe battleground.

PMID- 16619423
TI  - What is abortion?

PMID- 16619424
TI  - The politics of pain: rhetoric or reform?

PMID- 16619425
TI  - Is ethics for sale?... Juggling law and ethics in managed care.

PMID- 16619426
TI  - Care, communication and conversation.
AB  - The professionalisation of care has resulted in ever increasing specialisation,
      use of technical innovations and informatisation. This has had consequences for
      the level and way of involvement of the care provider vis-a-vis the patient. The
      result has been growing alienation on the part of the patient and flight into non
      classical medicine, as well as frustration on the part of medical personnel,
      likewise with respect to the reactions of patients. A solution is usually sought
      in more communication. This might be styled the professional answer to alienation
      and frustration, whereby 'the human factor', it is hoped, can be better accounted
      for. Enhanced communication implies two elements: 1) to better cater for the
      feelings of patients by trained communicators, i.e. more openness, more client
      satisfaction; 2) to better take into account patient rights and to actually
      implement them. The question is whether measures in terms of communication,
      geared at enhancing client satisfaction and the implementation of patient rights,
      are the real answer to the above mentioned alienation and frustration. Perhaps
      the trouble has deeper reasons and requires taking other dimensions into account
      such as decency and human dignity, which cannot be captured simply in terms of
      satisfaction and rights. This would mean that the answer must be sought at a
      deeper level than communication. This level might be called 'conversation' (using
      a concept analysed by Michael Oakeshott). In the second part of the paper, the
      possible relationship between care and conversation will be briefly analysed.

PMID- 16619427
TI  - The saving power of biotechnology: on public perceptions of a field of
      technology.
AB  - Biotechnology emerges in the nexus of academic, political and economic interests.
      With its strong reliance on a human individual capable of changing matter or
      organisms in accordance with anticipated goals, biotechnology is closely linked
      with a modern notion of human agency. In this article, it is argued that in
      contemporary European societies, biotechnology is perceived in three distinct
      ways, namely as an agent, as pluripotent, and as salvific. Similar to other forms
      of technologies, it provides a foil for human activity and projection, but it
      supersedes them in a quasi religious fashion. The great fascination with the
      biotechnological enterprise might, thus, express a more fundamental longing for
      narratives providing coherence and meaning.

PMID- 16619428
TI  - Public health, well-being and reciprocity.
AB  - Public-health measures are very effective and efficient means of improving
      health, yet public health is either neglected by the literature or fraught with
      unease, mainly due to the combination of the aggregate-distributive tension with
      the element of compulsion. I argue that this unease can be decreased by 1) a
      pluralist-holistic view of health, situating the normative value of health in its
      effect on well-being, incorporating both the objective and subjective source of
      the value of health; and 2) by a rich concept of reciprocity. This article
      supports Martha Nussbaum's critique of social-contract thinking for placing too
      much weight on the scale of normal functioning and productive reciprocity, as
      well as Sen's distinction between well-being and agency freedom. To reach an
      adequate understanding of the value and goal of public health within the general
      setting of health care, a pluralist conception of health, well-being and
      reciprocity is necessary.

PMID- 16619429
TI  - Professional ethics and collective professional autonomy: a conceptual analysis.
AB  - In the first section, it is argued that a professional activity involves
      systematic knowledge and proficiency, a form of continuous improvement of the
      related bodies of knowledge and proficiency, as well as two levels of
      understanding: a local one, which is the ability to justify and explain
      professional acts, and a global one, which involves a conception of the whole
      profession and its ethical principles. The second section is devoted to a
      conceptual analysis of professional ethics. It is argued that it consists of a
      general conception of professionality, a particular conception of the profession
      under consideration, and a conception of the normative requirements made by the
      societal envelope of the professional activity, in particular basic norms of
      democracy. The third section draws conclusions with respect to the nature and
      limits of professional autonomy. It is shown that such autonomy is much more
      restricted than its apparent extent. Examples from engineering and other
      professions are provided.

PMID- 16619430
TI  - Science, technology and ethics: from critical perspective to dialectical
      perspective.
AB  - It has been agreed upon, according to critical perspective, to distinguish the
      problems raised by scientific issues on the one hand and the problems raised by
      moral issues on the other. This distinction, at the genesis of theoretical
      ideology, postulates that experimental science is mere knowledge which, since it
      has nothing to do with action, cannot raise a moral problem. Yet the use of
      experimental techniques turns out to be a necessary means, although an
      insufficient one, to put to the test and to confirm the theoretical hypothesis of
      science. Thus, those techniques produce perceptible effects which can be
      assimilated to genuine transformation and are consequently capable of raising
      moral problems. It follows that the technical imperative of science can be
      conditioned by a moral imperative of technique, which leads to modification of
      the object of the research and dubs it, a dialectical object. It is, however,
      advisable to effect a demarcation between that which, within the frame work of
      research in experimental science, can pose a moral problem and which cannot. The
      criterion of refusability of practical projects, by analogy with Popper's
      criterion of refutability of theoretical conjectures, allows for this demarcation
      to be implemented. It postulates that only the technical projects of science,
      apart from scientific theories, can pose a moral problem or can be recognized as
      moral, providing that the conditions of a possible ethical refusal can be
      expressed. From the analysis and the synthesis of heterogeneous possibilities,
      dialectical perspective thus outlined represents an endeavour to go beyond
      critical perspective, while trying to seek an intermediary channel between the
      "progressist dogmatism" of science and the obscurantist scepticism" of morals.

PMID- 16619431
TI  - Human embryonic stem cell research: what's wrong with it?

PMID- 16619432
TI  - Tiptoeing around Roe.

PMID- 16619433
TI  - After the floods: health services' responsibilities in a crisis.

PMID- 16619434
TI  - Proceedings of the Symposium and Workshop on Biotechnology Derived Nutritious
      Foods: Challenges and Opportunities in Asia. February 29-March 1, 2004, Bali,
      Indonesia.

PMID- 16619435
TI  - Polio eradication programme: some ethical issues.

PMID- 16619436
TI  - Polio eradication and ethical issues.

PMID- 16619437
TI  - Emerging issues in medical imaging.

PMID- 16619438
TI  - Should this couple have undergone infertility treatment?

PMID- 16619439
TI  - Issues are complex and need innovative solutions.

PMID- 16619440
TI  - Infertility treatment is a human right.

PMID- 16619441
TI  - Should case documentations be used for research?

PMID- 16619442
TI  - Data can be used with safeguards.

PMID- 16619443
TI  - Use the data but take consent.

PMID- 16619444
TI  - Colonialism of clinical trials: discerning the positive spin offs.

PMID- 16619445
TI  - "Racially-tailored" medicine unraveled.

PMID- 16619446
TI  - More on authorship.

PMID- 16619447
TI  - California Stem Cell Research and Cures Act: what to expect from stem cell
      research?
AB  - On November 2, 2004 California voters approved Proposition 71, the California
      Stem Cell Research and Cures Act ("Act"), a $3 billion bond measure to advance
      stem cell research over the next ten years. The Act also created the California
      Institute for Regenerative Medicine (CIRM) and the Independent Citizens Oversight
      Committee (ICOC) which will govern the Institute, and make grants and loans for
      stem cell research and research facilities. This article will cover the history
      of the "Act", its potential impact on NIH's current stem cell program, and what
      are other states doing to compete with California's revolutionary efforts. In
      addition, the article will discuss the criteria for California's grant applicants
      under the Act and the legal issues surrounding the new discoveries funded by the
      Act.

PMID- 16619448
TI  - The medical examination in United States immigration applications: the potential
      use of genetic testing leads to heightened privacy concerns.
AB  - The medical examination has been an integral part of the immigration application
      process since the passing of the Immigration Act of 1891. Failing the medical
      examination can result in denial of the application. Over the years the medical
      examination has been expanded to include questioning about diseases that are
      scientifically shown to be rooted in an individual's genetic makeup. Recent
      advances in the fields of genomics and bioinformatics are making accurate and
      precise screening for these conditions a reality. Government policymakers will
      soon be faced with decisions regarding whether or not to sanction the use of
      these newly-developed genetic tests in the immigration application procedure. The
      terror threat currently facing the United States may ultimately bolster the
      argument in favor of genetic testing and/or DNA collection of applicants.
      However, the possibility of a government mandate requiring genetic testing raises
      a host of ethical issues; including the threat of eugenics and privacy concerns.
      Genetic testing has the ability to uncover a wealth of sensitive medical
      information about an individual and currently there are no medical information
      privacy protections afforded to immigration applicants. This article examines the
      potential for genetic testing in the immigration application process and the
      ethical issues surrounding this testing. In particular, this article explores the
      existing framework of privacy protections afforded to individuals living in the
      United States and how this and newly-erected standards like those released by the
      Health and Human Services (HHS) might apply to individuals seeking to immigrate
      to the United States.

PMID- 16619449
TI  - Government support for embryonic stem cell research.
AB  - State funding and political support for embryonic stem cell research facilitate
      progress.

PMID- 16619450
TI  - The impact of the HIPAA Privacy Rule on research participation.
AB  - HIPAA Privacy Rule significantly reduces the number of participants in research.

PMID- 16619451
TI  - Regulations limiting medical research in prisons remains necessary.
AB  - Protection of human subjects against medical research in prisons remains
      appropriate.

PMID- 16619452
TI  - [Max Delbruck].

PMID- 16619453
TI  - Life extension and creation: a reply to Silverstein and Boonin.

PMID- 16619454
TI  - Creation and abortion: a reply to Hall.

PMID- 16619455
TI  - Autonomy and informed consent on the Navajo Reservation.

PMID- 16619456
TI  - Neo-speciesism.

PMID- 16619457
TI  - Xenografting, species loyalty, and human solidarity.

PMID- 16619458
TI  - Against "humanism": speciesism, personhood, and preference.

PMID- 16619459
TI  - Physiological anthropology, human biology, and modern human variation.

PMID- 16619460
TI  - A social contract for deinstitutionalization.

PMID- 16619461
TI  - Marginal cases and moral relevance.

PMID- 16619462
TI  - Two moral strategies regarding abortion.

PMID- 16619463
TI  - Conscience, regulation and scientific misconduct.

PMID- 16619464
TI  - Seeing the self: the moral goals of service provision in the mental health
      sector.

PMID- 16619465
TI  - Ethics, identity, and new social movements in mental health services.

PMID- 16619466
TI  - Recombinant regulation: the Asilomar legacy 30 years on.

PMID- 16619467
TI  - From Asilomar to industrial biotechnology: risks, reductionism and regulation.

PMID- 16619468
TI  - Transnationalizing recombinant-DNA regulation: between Asilomar, EMBO, the OECD,
      and the European Community.

PMID- 16619469
TI  - The long and winding road from Asilomar to Brussels: science, politics and the
      public in biotechnology and regulation.

PMID- 16619470
TI  - Genetically modified survival: red and green biotechnology in Israel.

PMID- 16619471
TI  - Medical malpractice in Jewish law.

PMID- 16619472
TI  - Proceedings of the Perioperative Medicine Summit: Using Evidence to Improve
      Quality, Safety, and Patient Outcomes. September 22-23, 2005, Cleveland, Ohio,
      USA.

PMID- 16619473
TI  - Consensus statements on the BAHA system: where do we stand at present?
AB  - After more than 25 years of clinical experience, the BAHA (bone-anchored hearing
      aid) system is a well-established treatment for hearing-impaired patients with
      conductive or mixed hearing loss. Owing to its success, the use of the BAHA
      system has spread and the indications for application have gradually become
      broader. New indications, as well as clinical applications, were discussed during
      scientific roundtable meetings in 2004 by experts in the field, and the outcomes
      of these discussions are presented in the form of statements. The issues that
      were discussed concerned BAHA surgery, the fitting range of the BAHA system, the
      BAHA system compared to conventional devices, bilateral application, the BAHA
      system in children, the BAHA system in patients with single-sided deafness, and,
      finally, the BAHA system in patients with unilateral conductive hearing loss.

PMID- 16619474
TI  - Suppression of pro-metastasis phenotypes expression in malignant pleural
      mesothelioma by the PI3K inhibitor LY294002 or the MEK inhibitor UO126.
AB  - BACKGROUND: This study aimed to evaluate the impact of selective abrogation of
      either the MEK/ERK1/2 (UO126 or PD98059) or the PI3K/AKT (LY294002) signaling
      cascade on cell proliferation, motility and invasion and production of VEGF
      (collectively termed pro-metastasis phenotypes) in cultured malignant pleural
      mesothelioma (MPM) cells. MATERIALS AND METHODS: Treatment-induced cytotoxicity
      was evaluated by MTT or Annexin V assays. Cell motility was assessed by wound
      healing and Matrigel invasion assays. VEGF in conditioned media of cancer cells
      was measured by ELISA. RESULTS: LY294002 and UO126 significantly inhibited cell
      proliferation and clonogenicity of MPM cells in vitro. A substantial reduction of
      cell motility, Matrigel invasion as well as inhibition of basal or EGF-induced
      VEGF production were observed in drug-treated cells. CONCLUSION: The selective
      MEK or PI3K kinase inhibitors are equally effective in down-regulating the
      expression of pro-metastasis phenotypes, suggesting that MEK or PI3K are
      appropriate targets for the development of molecular therapeutics for malignant
      pleural mesothelioma.

PMID- 16619475
TI  - Role of bcl-2 in endometrioid corpus cancer: an experimental study.
AB  - BACKGROUND: Bcl-2 expression appears to be under hormonal control in normal
      endometrium and to correlate with hormone receptor status in endometrial cancer.
      The aim of this study was to assess bcl-2 expression in endometrial cancer.
      MATERIALS AND METHODS: Hysterectomy specimens from 125 patients with endometrial
      cancer were stained for bcl-2. Estrogen receptor (ER) and progesterone receptor
      (PR) levels were quantified with a dextran-coated charcoal assay. RESULTS: Bcl-2
      expression correlated significantly with endometrioid histology and high levels
      of ER and PR (p < 0.05). For the entire population, bcl-2 expression was not
      significantly associated with the presence of extrauterine disease. However, when
      only patients with grade 1 or 2 endometrioid histology were considered, tumors
      with bcl-2 expression were significantly (p < 0.05) more likely to present with
      extrauterine disease than those not expressing bcl-2. CONCLUSION: Bcl-2-mediated
      inhibition of apoptosis may be important in the acquisition of molecular
      alterations and development of metastases in a subset of hormone-dependent
      endometrial cancers.

PMID- 16619476
TI  - Differences in human papillomavirus type may influence clinical outcome in early
      stage cervical cancer.
AB  - BACKGROUND: The presence of human papillomavirus (HPV), the HPV type and viral
      load in early stage cervical carcinoma were investigated in order to elucidate
      whether any of these factors were important for clinical outcome. PATIENTS AND
      METHODS: Twelve patients who were disease-free 5 years after diagnosis were
      matched and compared with 12 patients who died within 2 years. The presence of
      HPV, HPV type and viral load in their tumours was examined by PCR. RESULTS: The
      distribution and load of HPV was similar in the 2 patient groups. HPV-16 was,
      however, significantly more common in tumours of the surviving patients than in
      those of patients who died (88.9% and 18.2%, respectively, p = 0.0152).
      CONCLUSION: HPV-16 was significantly more common in early stage carcinomas of
      patients surviving more than 5 years in comparison to early stage carcinomas of
      patients with a poor prognosis.

PMID- 16619478
TI  - JAS-R, a new megakaryo-erythroid leukemic cell line that secretes erythropoietin.
AB  - BACKGROUND: The processes of leukemogenesis and differentiation of the megakaryo
      erythroid lineage remain poorly understood. Leukemic cell lines derived from
      megakaryocytic leukemia are valuable reagents for studies on these events.
      MATERIALS AND METHODS: A new cell line, JAS-R, was established from a 64-year-old
      patient with acute megakaryocytic leukemia (AML M7). Its characteristics were
      studied by morphological, immunophenotypic and molecular biological analysis.
      RESULTS: Immunophenotyping showed that the JAS-R cells were positive for CD33,
      CD41 and CD61, as well as moderately to weakly positive for CD4, CD7, CD13 and
      glycophorin A. Chromosomal analysis revealed a composite karyotype, but no major
      translocation abnormalities were observed. Electron microscopy disclosed that the
      JAS-R cells had numerous surface blebs and some cells also had alpha-granules and
      demarcation membranes. The mRNAs of 4 major proteins (platelet factor 4, beta
      thromboglobulin, selectin-P and thrombospondin 1) found in alpha-granules were
      all expressed by the JAS-R cells. In particular, expression of platelet factor 4
      was high. To further characterize JAS-R cells, comparison with 4 other megakaryo
      etythroid cell lines (CMK, MEG-01, K562 and KU812) was done by gene expression
      profiling using an oligo-DNA microarray. The results showed that JAS-R was a
      distinctive cell line. It was noteworthy that the JAS-R cells secreted
      erythropoietin and expressed erythropoietin receptor. A neutralizing antibody for
      erythropoietin partly inhibited the proliferation of the cells. CONCLUSION: JAS-R
      may be a useful cell line for investigating the differentiation and
      leukemogenesis of megakaryo-erythroid cells and for studying the influence of
      erythropoietin on these cells.

PMID- 16619477
TI  - Regulation of human neurotropic JCV in colon cancer cells.
AB  - BACKGROUND: Recently, the genome of the human polyomavirus, JC (JCV), and
      expression of its early and late regulatory proteins (T-antigen and agnoprotein)
      have been demonstrated in neoplastic cells of colonic cancer cases. MATERIALS AND
      METHODS: Regulation of JCV was investigated in a human colon cancer cell line
      (SW480) and compared to a human glioblastoma cell line (U87-MG) that is
      permissive for JCV replication. RESULTS: SW480 cells supported basal
      transcription of both early and late JCV promoters. The expression of TCF-4, a
      component of Wnt signaling, modulated JCV transcription in a cell type-specific
      manner. Both TCF-4 and T-antigen bound to the JCV promoter region and bound to
      each other. In addition, the expression of TCF-4 caused a decrease in the ability
      of the T-antigen to stimulate viral DNA replication in U87-MG cells. CONCLUSION:
      Wnt pathway signaling proteins and T-antigen interact to regulate JCV in colonic
      epithelial cells.

PMID- 16619479
TI  - Hypermethylation in the p16 promoter region in the carcinogenesis of endometrial
      cancer in Japanese patients.
AB  - BACKGROUND: p16 has been reported to disappear by hypermethylation in various
      cancers. However, the relationship between the frequency of hypermethylation of
      p16 and the mechanism of its inactivation has not been completely elucidated in
      endometrial cancer. MATERIALS AND METHODS: Hypermethylation in the promoter
      region of the p16 gene and the expression of the p16 protein in 51 specimens,
      including 8 endometrial cancer cell lines, 7 normal endometrial tissues, 12
      atypical endometrial hyperplasia tissues and 32 endometrial cancer tissues were
      analyzed. RESULTS: Five out of 8 endometrial cancer cell lines showed
      hypermethylation with high frequency, although only 1 showed loss of gene
      expression. However, no endometrial cancer tissue of the 32 specimens showed
      hypermethylation. Furthermore, loss of expression was immunohistochemically
      observed in 3 out of the 20 specimens. CONCLUSION: These results suggest that
      hypermethylation of p16 rarely occurs and, thus, has no significant effect on the
      carcinogenesis of endometrial cancer in Japanese patients.

PMID- 16619480
TI  - Mechanisms of the growth-inhibitory effect of the RNase-EGF fused protein against
      EGFR-overexpressing cells.
AB  - BACKGROUND: We previously showed the usefulness of a fused protein of human
      pancreatic ribonuclease1 (hRNase1) with human epidermal growth factor (hEGF) for
      molecular targeting of EGF receptor (EGFR)-overexpressing cells. In this study,
      the mechanisms underlying the inhibition of cell growth by RNase-EGF fused
      proteins was confirmed. MATERIALS AND METHODS: Des.1-7 hRNase1 was genetically
      fused to hEGF. The fused proteins were expressed and isolated from Escherichia
      coli. The internalization of hRNase1-hEGF was confirmed by confocal fluorescence
      microscopy. The growth-inhibitory effect of the fused proteins was evaluated by
      MTT assay. RESULTS: FITC-labelled hRNase1-hEGF was internalized into EGFR
      overexpressing A431 cells. The internalization was not observed in A431 cells pre
      treated with hEGF and EGFR-deficient H69 cells. The growth-inhibitory effect of
      des.1-7 hRNase1-hEGF against A431 cells was statistically significantly more
      pronounced than that of hRNase1-hEGF. CONCLUSION: RNase-EGF fused proteins are
      internalized through EGFR and inhibit cell growth by exerting their
      ribonucleolytic activity in the cytosol.

PMID- 16619481
TI  - Models of monocytic invasion into glioma cell aggregates.
AB  - BACKGROUND: In order to investigate why human gliomas are abundantly infiltrated
      by monocytic cells without signs of antitumor activity, experimental models were
      established in vitro and in vivo. MATERIALS AND METHODS: Peripheral human blood
      monocytes were added to A172 or U118 glioma cell spheroids and probes analyzed
      after 72 h by immunohistochemistry. Fluorescence-labelled peritoneal macrophages
      were administered to syngeneic RG2-glioma-bearing Fischer rats by intravenous or
      intracarotid injection. RESULTS: Spheroids of both cell lines were infiltrated by
      monocytes, which took on a chronic inflammatory phenotype with co-expression of
      MRP8 and MAC 387/MRP14 and positivity to 25F9, but not to 27E10. After both intra
      arterial and intravenous injection, labelled monocytes accumulated within the
      tumor parenchyma of the rat gliomas, while the surrounding brain was only
      sparsely infiltrated. CONCLUSION: The experimental models described here allow
      for further investigation of the interactions between monocytes and glioma cells,
      both in vitro and in vivo. Moreover, monocytes that infiltrate from the
      peripheral blood into brain tumors may serve as carriers for targeted therapies.

PMID- 16619482
TI  - Therapeutic properties of DNA-based fibroblast and dendritic cell vaccines in
      mice with squamous carcinoma.
AB  - BACKGROUND: Dendritic cells (DC) express class I/II MHC-determinants and co
      stimulatory molecules required for T cell activation. In a mouse model of
      squamous cell carcinoma (SCC), we compared the immunogenic properties of
      allogeneic DNA-based fibroblast vaccines, which are taken up and processed by DC
      of the host, and syngeneic DNA-based DC vaccines, which present antigens
      directly. The incentive was the important practical advantages of using
      fibroblasts rather than DC in generating vaccines for the immunotherapy of SCC.
      MATERIALS AND METHODS: The fibroblast vaccine was prepared by transfer of genomic
      DNA-fragments (25 kb) from relatively small numbers (10(7) = 64 mm3 tumor) of
      SCCVII/SF cells into LM cells, a mouse fibroblast cell line (H-2(k)). SCCVII/SF
      cells are a highly aggressive squamous carcinoma cell line of C3H/He mouse origin
      (H-2(k)). As the transferred DNA spontaneously integrates into the genome of the
      recipient cells, and is replicated as the cells divide, the number of transfected
      fibroblasts could be conveniently expanded for repeated immunizations. Syngeneic
      DC, rather than fibroblasts, were also used as the recipients of DNA from the
      SCC. C3H/He mice, highly susceptible to growth of SCCVII/SF cells, were immunized
      with either the DNA-based fibroblast or the DNA-based DC vaccine and the
      antitumor immune responses were compared. RESULTS: Robust CD8+ T cell-mediated
      antitumor immunity sufficient to deter the growth of the neoplastic cells was
      generated in mice immunized with the transfected fibroblasts, but not in mice
      immunized with the transfected DC. CONCLUSION: These data raise the possibility
      that an analogous strategy could be used to treat squamous carcinoma patients
      with minimal residual disease after primary therapy.

PMID- 16619483
TI  - Expression of ABC transporters in human hepatocyte carcinoma cells with cross
      resistance to epirubicin and mitoxantrone.
AB  - BACKGROUND: In order to understand the cross-resistance between epirubicin (EPI)
      and mitoxantrone (MIT), EPI- and MIT-resistant cells were established and their
      cross-resistance was evaluated. MATERIALS AND METHODS: The degrees of growth
      inhibition of EPI-resistant HLE-EPI cells and MIT-resistant HLE-MIT cells by
      anticancer drugs were measured. The mRNA expressions of multidrug resistance
      protein 1 (MDR1)/ABCB1 and breast cancer resistance protein (BCRP)/ABCG2 were
      also measured by quantitative real-time RT-PCR. Moreover, intracellular
      accumulation of EPI was investigated. RESULTS: HLE-EPI cells were resistant to
      EPI, MIT and docetaxel. HLE-MIT cells were resistant to EPI, MIT and SN-38. HLE
      EPI cells overexpressed MDR1 and HLE-MIT cells overexpressed BCRP. The
      intracellular accumulation of EPI was decreased in HLE-EPI and HLE-MIT cells.
      CONCLUSION: The results suggest that both MDR1 and BCRP can up-regulate the
      efflux of EPI causing resistance to EPI in HLE-EPI and HLE-MIT cells.

PMID- 16619484
TI  - Conjugated linoleic acid (CLA) modulates prostaglandin E2 (PGE2) signaling in
      canine mammary cells.
AB  - BACKGROUND: Conjugated linoleic acid (CLA), a naturally occurring linoleic acid
      isomer found in ruminant-produced foods, has the potential to serve as an
      effective chemopreventive nutriceutical factor for breast cancer prevention based
      upon previous published studies. There are several CLA isomers in ruminant
      produced food products, among which t10,c12-CLA and c9,t11-CLA are more potent.
      Expression of cyclooxygenase 2 (COX-2) in mammary tumors has been correlated with
      poor prognosis. Prostaglandin E2 (PGE2) is a major COX-2 product in various
      cancers and, as in humans, PGE2 concentrations in canine tumor tissues were
      frequently elevated. Moreover, a PGE2 receptor subtype, EP2, is highly expressed
      in mammary tumors. Thus, various studies have implicated the important role of
      PGE2 and EP2 in COX-2-regulated tumor development. MATERIALS AND METHODS: Mammary
      tumor and normal mammary tissues were both collected from a female dog with
      mammary tumor. Both malignant and normal mammary tissues were subjected to
      isolation of epithelial and stromal cells. The effects of t10,c12-CLA and c9,t11
      CLA on proliferation, as well as COX-2 and EP2 protein expression in canine
      mammary normal and cancerous cells, were detected by CellTiter 96 AQueous assay
      and Western blot assay, respectively. RESULTS: Both t10,c12-CLA and c9,t11-CLA
      not only suppressed malignant mammary cell growth, but also exerted inhibitory
      effects on tumor-associated non-malignant mammary cells. Similarly, both t10,c12
      CLA and c9,t11-CLA suppressed EP2 protein expression in both normal and malignant
      mammary cells. t10,c12-CLA was more effective in decreasing COX-2 protein
      expression in malignant mammary cells, while, in contrast, c9,t11-CLA down
      regulated COX-2 protein expression in both normal and malignant mammary cells.
      CONCLUSION: The results indicate that the dietary component CLA regulates COX-2
      and EP2 protein expression in both malignant mammary cells and cells from the
      tumor-associated stromal compartment. In turn, this may suppress PGE2 signaling,
      leading to better prognosis. We further speculate that the knowledge obtained
      from canine studies may also be beneficial to study human breast cancer.

PMID- 16619485
TI  - Selenium protection from DNA damage involves a Ref1/p53/Brca1 protein complex.
AB  - Selenium, in the form of seleno-L-methionine (SeMet), induced Redox-factor-1
      (Ref1) and p53 proteins in normal human and mouse fibroblasts. Ref1 and p53 are
      known to be associated with each other, resulting in enhanced sequence-specific
      DNA binding by p53 and transactivation of p53-regulated effector genes. SeMet
      preferentially induced the DNA repair branch of the p53 pathway, while apoptosis
      and cell cycle arrest were unaffected. Accordingly, pretreatment with SeMet
      protected normal fibroblasts from subsequent DNA damage. In the current study,
      Brca1 and Ref1 were shown to interact concurrently with p53 in targeting a SeMet
      induced DNA repair response. Moreover, like p53 and Ref1, Brca1 was required for
      SeMet-mediated DNA damage protection, as brca1 -/- mouse fibroblasts were not
      protected from UV-radiation by SeMet treatment. These findings indicate that
      besides p53 and Ref1, Brca1 is required for selenium protection from DNA damage.
      The data are consistent with selective induction of the DNA repair branch of the
      p53 pathway by SeMet.

PMID- 16619486
TI  - Rin1 is a negative regulator of the IL3 receptor signal transduction pathways.
AB  - Cytokines interact with cell-surface receptors, initiating signaling cascades
      that promote cell growth while inhibiting the pathways of apoptotic cells. Rin1
      is a multifunctional protein that has been shown to regulate EGF receptor
      signaling and endocytosis. To examine the role of Rin1 in IL3 receptor signaling
      pathways, Rin1 and deletion mutants were expressed in cells using a retrovirus
      system. In this study, the overexpression of Rin1 molecules was shown to
      selectively block IL-3 activation of the Ras-Erk1/2 and PI3K/Akt pathways and the
      IL-3-stimulated incorporation of [3H] thymidine into DNA without a significant
      effect on the activity of the JNK and p38K pathways. Moreover, the depletion of
      Rin1 by RNA interference induced cell growth. In addition, Rin1 was also required
      as a downstream effector of BCR/ABL-induced cell proliferation. Interestingly,
      the expression of Rin1 selectively blocked the activation of Erk1/2 induced by
      the BCR/ABL oncogene. These results demonstrate that Rin1 plays an essential and
      selective role in both IL3- and BCR/ABL-induced cell proliferation and highlight
      a new function for Rin1 in leukemic cells.

PMID- 16619488
TI  - Analysis of the HER2/neu gene amplification in microdissected breast cancer
      tumour samples.
AB  - The HER2/neu oncogene has been reported to be amplified in > 20% of invasive
      ductal carcinomas. In order to investigate the HER2/neu status in pure
      populations of breast cancer cells, a laser capture microdissection (LCM) system
      was used. Formalin-fixed paraffin-embedded breast tissue areas corresponding to
      normal ducts, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC)
      were microdissected and genomic DNA was isolated by a modified proteinase K-
      phenol extraction method and subjected to PCR for HER2/neu analysis. One hundred
      % concordance for detection of the HER2/neu gene amplification was found between
      immunohistochemistry and PCR used in combination with LCM. Our results indicated
      that LCM is a powerful technique for isolating pure populations of cells from
      paraffin-embedded tissue sections and that these cells can be used to study
      genomic alterations at the DNA level.

PMID- 16619487
TI  - Comparative evaluation of FET and FDG for differentiating lung carcinoma from
      inflammation in mice.
AB  - BACKGROUND: Clinical FDG/PET (2-deoxy-2-18F-fluoro-D-glucose/positron emission
      tomography) studies encounter difficulties in detecting early stage lung cancers.
      The aim of this study was to evaluate the ability of O-2-18F-fluoroethyl-L
      tyrosine (FET) and FDG to differentiate between inflammation and lung carcinoma
      in mice. MATERIALS AND METHODS: Sixty-four C57BL/6 mice were inoculated with
      2x10(6) LLC1 lung carcinoma cells in the right hind flank on day 0 and were then
      injected with 0.1 mL turpentine in the left thigh muscle on day 3. The progress
      of inflammation and tumor in mice was longitudinally monitored by FDG/microPET.
      The biodistribution study, pharmacokinetic evaluation and whole-body
      autoradiography of FET and FDG were performed on day 8 after tumor inoculation.
      RESULTS: The FDG uptakes in tumor and inflammatory lesions were 4.42-fold and
      3.53-fold (n = 4) higher, respectively, than that in muscle at 90 min post
      injection and the tumor-to-inflammation ratio was 1.25. For FET/microPET, the
      tumor uptake was 2.07-fold and 2.07-fold (n = 4) higher than those in muscle and
      inflammatory lesions at 90 min post-injection, respectively. The distribution
      half-life (t1/2,alpha) and the elimination half-life (t1/2,beta) of FET were 39
      min and 205 min, respectively, in mice. CONCLUSION: FDG delineated both tumor and
      inflammation, while FET accumulated in tumor to a significantly higher extent.
      Our results demonstrated the potential of FET to distinguish epidermoid lung
      carcinoma from inflammatory lesions in mice.

PMID- 16619489
TI  - P16 protein abnormality in Epstein-Barr virus-associated gastric carcinomas.
AB  - BACKGROUND: The Epstein-Barr virus (EBV) has been detected in lymphoepithelioma
      of the nasopharynx and lymphoepithelioma-like carcinomas in various organs. Ten
      percent of gastric carcinomas, including lymphepithelioma-like carcinoma and
      adenocarcinoma, are associated with EBV infection. The p16 protein is a cyclin
      dependent kinase (CDK) inhibitor that decelerates the cell cycle, inactivating
      the CDKs that phosphorylate retinoblastoma (Rb) protein. MATERIALS AND METHODS:
      To clarify the relationship between p16 overexpression and EBV-associated gastric
      carcinomas, immunohistochemical analysis of p16 and detection of EBV by in situ
      hybridization were performed on 238 formalin-fixed and paraffin-embedded samples
      of gastric carcinomas. RESULTS: The non-expression of p16 protein in EBV-positive
      and -negative carcinoma was 81.5% (53 out of 65 samples) and 26.6% (46 out of 173
      samples), respectively (p < 0.001). CONCLUSION: We suggest that the
      carcinogenesis of EBV-associated gastric cancers may be closely associated with a
      p16 abnormality.

PMID- 16619490
TI  - Anticancer activity of MS-275, a novel histone deacetylase inhibitor, against
      human endometrial cancer cells.
AB  - BACKGROUND: Histone deacetylase inhibitors (HDACIs) can inhibit cell
      proliferation, induce cell cycle arrest and stimulate apoptosis of cancer cells.
      MATERIALS AND METHODS: The effects of a novel HDACI, MS-275, on 4 endometrial
      cancer cell lines and normal human endometrial epithelial cells was investigated.
      Endometrial cancer cells were treated with various concentrations of MS-275 and
      its effect on cell growth, cell cycle, apoptosis and related measurements was
      investigated. RESULTS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assays showed that all endometrial cancer cell lines were sensitive to
      the growth inhibitory effect of MS-275, although the normal endometrial
      epithelial cells were viable after treatment with the same doses of MS-275 that
      induced growth inhibition in endometrial cancer cells. The cell cycle analysis
      indicated that their exposure to MS-275 induced the G0/G1 arrest of the cell
      cycle. Induction of apoptosis was confirmed by annexin V staining of externalized
      phosphatidylserine and loss of the transmembrane potential of mitochondria. This
      induction occurred in concert with altered expression of genes related to cell
      growth, malignant phenotype and apoptosis. CONCLUSION: These results raise the
      possibility that MS-275 may prove particularly effective in the treatment of
      endometrial cancer.

PMID- 16619491
TI  - Rocaglaol induces apoptosis and cell cycle arrest in LNCaP cells.
AB  - Rocaglaol is a cytotoxic cyclopenta[b]benzofuran isolated from the bark of Aglaia
      crassinervia. It exhibited in vitro cytotoxic activity against Lu1, LNCaP and MCF
      7 cells with ED50 values of 13.8, 23.0 and 9.2 nM, respectively. DAPI staining
      indicated that LNCaP cells treated with rocaglaol underwent apoptosis. In order
      to determine whether rocaglaol-induced apoptosis is mediated by the mitochondrial
      pathway, apoptosis-related mitochondrial-associated proteins were studied.
      Rocaglaol treatment induced Bax expression through 12 to 72 h of exposure, while
      Bcl-xl expression was slightly decreased through 48 h, and decreased more
      significantly by 72 h. Cleaved caspase-9 expression was detected at 72 h, and
      cleaved caspase-7 was increased through 48 to 72 h. Consequently, the large
      fragment (89 kDa) of PARP resulting from caspase cleavage was detected at 12, 24
      and 48 h, and especially at 72 h. Cleaved PARP expression was also detected at 72
      h. Since rocaglaol caused dose-dependent G2/M phase arrest of LNCaP cells as
      indicated by flow cytometric analysis, the protein levels of cell cycle-related
      genes were measured. Rocaglaol treatment (230 nM) did not change cyclin B after
      24- to 60-h treatment. The expression of cdc2 was not changed and phospho-cdc2
      (Tyr 15) increased after 36-, 48- and 60-h treatment. In addition, protein
      phosphatase Cdc25C, which functions as a mitotic activator by dephosphorylation
      of Cdc2, decreased in a time-dependent manner after rocaglaol treatment. Taken
      together, these results suggest that rocaglaol is a potent anticancer drug that
      induces apoptosis of LNCaP cells through the mitochondrial pathway and its G2/M
      phase cell cycle arrest is associated with the down-regulation of Cdc25C and the
      dephosphorylation of Cdc2.

PMID- 16619492
TI  - Chromosome 1 abnormalities in multiple myeloma.
AB  - Multiple myeloma (MM) is a malignancy of the terminally-differentiated B cells
      and accounts for 10% of all hematological malignancies. Chromosome 1 aberrations
      are frequently described, the short arm being preferentially involved in
      deletions and the long arm in gains. The abnormalities were identified in the
      bone marrow of 37 MM patients by conventional cytogenetics. Fluorescence in situ
      hybridization (FISH) was used to confirm the presence of the abnormalities and to
      better characterize them. Chromosome 1 abnormalities were grouped into 4
      categories: balanced translocations, deletions, amplifications and jumping
      translocations (JT). Breakpoints involved in balanced translocations were
      randomly distributed. The smallest region of overlap for deletions was 1p11 -->
      1p21 (present in 27% of the patients) and for gains 1q31 --> 1qter (present in
      54% of the patients). The whole long arm was found to be the donor segment for
      the majority of patients with JT, the most frequent recipients being chromosomes
      16 and 19. Our results share some similarities with those obtained for 143
      published patients studied by FISH. Band 1p21 was found to be frequently deleted,
      leading to the assumption that a 1p deletion could lead to hemizygosity of at
      least 1 tumor suppressor gene. Two regions of 1q showed preferential gains: q12
      to q22 and q31 to q42; these amplifications could induce the overexpression of 1
      or more oncogenes. In conclusion, our results confirm that chromosome 1
      abnormalities play an important role in the pathogenesis of multiple myeloma.

PMID- 16619494
TI  - Arising podosomal structures are associated with neoplastic cell morphological
      phenotype induced by the microenvironment.
AB  - Increased numbers of rosettes of podosomes were observed in overgrown rat Rous
      sarcoma RsK4 cells. A possible role of these structures in nutrient uptake in
      tumour cell survival was investigated by exposure to acute starvation. A single
      cell suspension of RsK4 cells in Hanks balanced salt solution was allowed to
      interact with either clean uncoated or serum-coated for bait coverglasses.
      Confocal microscopy revealed contrasting 3D cell morphologies that were
      associated with conspicuous patterns of podosomal structures, which on the coated
      coverglasses resembled the sealing zones of osteoclasts, while on the uncoated
      coverglasses they resembled the marginal podosomes of migrating monocyte-derived
      cells. Thus, the arising podosomal structures, the involvement of which in an
      uptake of nutrients appeared feasible morphologically, were associated with the
      emerging 3D cell shapes guided by the microenvironment. Such phenotypic
      plasticity of neoplastic RsK4 cells in response to microenvironmental challenge
      suggested that uniqueness in cellular attributes within the neoplastic cell
      population could be crucial for the malignant potential.

PMID- 16619493
TI  - Enhanced motility of KGF-transfected breast cancer cells.
AB  - BACKGROUND: In a previous study, we reported that keratinocyte growth factor
      (KGF) produced a rapid increase in the motility of ER-positive breast cancer
      cells. Others have demonstrated that KGF treatment in rodent species produces
      rapid mammary ductal hyperplasia. Epithelial cells do not produce KGF; thus, in
      the present study, MCF-7 cells were stably transfected with a KGF-expressing
      vector and the motility and morphology of the transfected, non-transfected and
      empty vector cell lines compared. MATERIALS AND METHODS: A mammalian expression
      vector containing a KGF cDNA was transfected into MCF-7/beta cells, and two
      stable clones (MCF-7/beta/KGF-T8 and MCF-7/beta/KGF-T9) were identified. Western
      blotting of conditioned medium from these clones was used to confirm the
      expression of KGF. The motility of wild-type and KGF-transfected MCF-7 cells was
      compared using time-lapse videomicroscopy and a cell culture wounding model which
      examined cell migration over a period of 1-3 days. RESULTS: The Western blots
      demonstrated that the expression of KGF in both the MCF-7/beta/KGF-T8 and MCF
      7/beta/KGF-T9 cell lines was higher than the wild-type and MCF-7/beta cell lines.
      The cell proliferation and migration distance was significantly greater for both
      KGF-transfected MCF-7 cell lines than the wild-type and MCF-7/beta cell lines
      under the same experimental conditions. Further, changes in motile morphology
      were observed in both the MCF-7/beta/KGF-T8 and MCF-7/beta/KGF-T9 cell lines. In
      addition, the MCF-7/beta/KGF-T8 clone was found to produce much larger tumors
      than both the MCF-7/beta/KGF-T9 and EV clones in mouse xenografts. These results
      indicated that autocrine production of KGF in the KGF-transfected MCF-7 cell
      lines enhanced cell migration, migration-related morphology and xenograft tumor
      growth. CONCLUSION: KGF-transfected MCF-7 cells displayed a much greater motility
      than non-transfected cells, confirming the KGF motility enhancement effect which
      we previously reported. The use of KGF-transfected breast cancer cells in the
      xenograft model may help to study the mechanism of KGF-mediated cell motility and
      to identify specific KGF antagonists that may be used to prevent or impede KGF
      mediated metastatic progression.

PMID- 16619495
TI  - Quantitative immunohistochemical and in situ hybridization analysis of
      metalloproteinases in prostate cancer.
AB  - The role of matrix metalloproteinases (MMPs) as markers of tumor progression in
      prostate cancer (CaP) is complex and poorly understood. Using computerized image
      analysis, the differential expression of interstitial collagenase (MMP-1),
      gelatinase B (MMP-9), matrilysin-1 (MMP-7) and the membrane-type 1-MMP (MT1-MMP)
      in the epithelium and stroma of human prostate neoplastic tissues were
      investigated. Using immunohistochemistry and in situ hybridization techniques, 38
      paraffin-embedded prostatic samples were analyzed and CaP was compared with
      prostate intraepithelial neoplasia (PIN) and its normal adjacent prostate (NAP)
      counterpart. The association of MMP protein and mRNA expression with Gleason
      histological tumor grade and TNM clinical stage was also determined. In most
      prostatectomy specimens examined, detectable amounts of MMP-1, MT1-MMP, MMP-7 and
      MMP-9 proteins and MT1-MMP and MMP-9 mRNA were found in the epithelial and
      stromal components of CaP, PIN and NAP. MMP expression was significantly stronger
      in the epithelium than in the stroma (p < 0.01). In the epithelium of normal and
      preneoplastic prostate tissue, MMP-1, MMP-9 and MT1-MMP were preferentially
      expressed in secretory luminal cells; conversely, MMP-7 was concentrated in basal
      cells. Epithelial and stromal expressions of MMPs differed in normal,
      preneoplastic and CaP tissues. Whereas MMP-1 was overexpressed in NAP epithelial
      glands and progressively decreased from PIN to CaP, MMP-7, MMP-9 and MT1-MMP were
      more strongly expressed in CaP than in PIN and NAP tissue. The MMPs investigated
      reached their highest levels in prostate tumors with high Gleason scores. The
      differential MMP expression in epithelial and stromal prostate tissue supports
      the previous hypothesis that MMPs may be autocrine and paracrine mediators of the
      stroma-epithelial interaction, an event that plays a critical role in regulating
      normal and abnormal prostate growth. MMP gene regulation changes during the early
      stage of prostate cancer. Differential expression of MMP components in CaP may
      reflect the malignant phenotype and more aggressive tumor behavior.

PMID- 16619496
TI  - P53R2, p53 inducible ribonucleotide reductase gene, correlated with tumor
      progression of non-small cell lung cancer.
AB  - p53R2 plays a crucial role in supplying dNTPs for DNA repair. The expression of
      p53R2 is induced by DNA-damaging agents in a p53-dependent manner and p53R2
      translocates to the nucleus upon DNA damage. Immunohistochemistry was used to
      analyze the protein expression of p53R2 in paraffin-embedded tumor samples from
      130 well-characterized non-small cell lung cancer (NSCLC) patients and the
      expression level of p53R2, clinical variables and survival outcome were compared.
      A positive expression of p53R2 was detected in the cytoplasm of tumor cells in 61
      of the 130 patients (46.2%) with NSCLC. The positive ratio was significantly
      higher in the patients with pathological stage II/III, pathological T3-4 and
      pathological N1-3 than in those with stage I, T1-2 and N0, respectively. No
      significant difference was observed between the p53R2 expression and the gender,
      age at operation, histological type or p53 expression. Though our findings do not
      support that the p53R2 immunocytochemical marker alone plays an important
      prognostic role in NSCLC, the DNA repair pathway mediated by p53R2 may be
      responsible for controlling the growth of lung cancer.

PMID- 16619497
TI  - Evaluation of combined nedaplatin and docetaxel therapy for human head and neck
      cancer in vivo.
AB  - BACKGROUND: Nedaplatin (NDP) was developed as a second-generation platinum
      complex. The antitumor efficacy of the combination of NDP with docetaxel (TXT)
      was evaluated against human head and neck carcinoma. The antitumor activity of
      NDP plus TXT was compared with that of some other platinum compounds, cisplatin
      (CDDP) and carboplatin (CBDCA) plus TXT. MATERIALS AND METHODS: Mice implanted
      with HNC-3 or KB3-1, human head and neck carcinoma were administered i.v. NDP,
      CDDP or CBDCA plus TXT. RESULTS: The antitumor efficacy was enhanced
      significantly by the combination of NDP with TXT. Combined NDP plus TXT treatment
      exerted antitumor efficacy comparable to that of combined CDDP plus TXT
      treatment. Thrombocytopenia induced by NDP was not enhanced by the combination of
      NDP and TXT. CONCLUSION: The results suggest that combined NDP and TXT can
      alleviate thrombocytopenia caused by NDP and that this combination may have
      significant potential in clinical use.

PMID- 16619498
TI  - PSC 833, an inhibitor of P-glycoprotein inhibits 1,2-dimethylhydrazine-induced
      colorectal carcinogenesis in male Fischer F344 rats.
AB  - BACKGROUND: The expression of P-glycoprotein (Pgp) is intimately associated with
      cancer development. In order to explore the therapeutic value of Pgp as a target
      for chemotherapy, we studied the effect of PSC 833 (PSC), a potent inhibitor of
      Pgp, on 1,2-dimethylhydrazine (1,2-DMH)-initiated colorectal carcinogenesis in
      rats. MATERIALS AND METHODS: Male Fischer 344 rats, initiated with 1,2-DMH
      coupled with partial hepatectomy, were exposed to dietary 1% orotic acid for 22
      weeks. They were then fed either the AIN93G basal diet (BD) or BD containing PSC
      (a daily dose of 15 mg/kg body weight) for 35 weeks. RESULTS: PSC significantly
      inhibited colorectal tumor multiplicity by 53% and tumor burden by 74%. PSC
      mediated inhibition was evident in tumors as small as 2 mm in diameter and
      remained effective throughout the course of tumor growth. Histological assessment
      showed that PSC significantly inhibited tumor progression to colorectal
      adenocarcinoma by 63%. CONCLUSION: Collectively, this study indicates that PSC
      inhibited experimental colorectal carcinogenesis initiated with 1,2-DMH in rats.

PMID- 16619499
TI  - Low adhesiveness coupled with high superinvasiveness in vitro predicts the in
      vivo metastatic potential of a mouse mammary adenocarcinoma cell line.
AB  - BACKGROUND: We have previously shown that the selection of cancer cell lines with
      chemotherapeutic agents can alter the invasive potential of the cells, resulting
      in a superinvasive phenotype, where cells not only invade through matrigel and
      migrate through membrane pores, but also subsequently detach from the underside
      of the invasion chamber, survive in suspension and ultimately attach to and grow
      on the bottom of the well beneath the insert. In order to determine the
      significance of this in vivo, the following experiments were performed. MATERIALS
      AND METHODS: 4T1-GFP mouse mammary adenocarcinoma cells were pulse-selected with
      doxorubicin or paclitaxel. Three variants with differing invasiveness were
      isolated and their metastatic potential in vivo was compared to the parental cell
      line, through injection into the mammary fat pad of BALB/c mice and subsequent
      primary tumour growth and metastasis to the lungs measurement. RESULTS:
      Increasing superinvasiveness was inversely linked to tumour diameter (p < 0.005).
      The superinvasive status predicted the incidence of lung nodules in 2/3 variant
      groups, with significant differences in the number of nodules (p < 0.001).
      CONCLUSION: The in vitro superinvasive phenotype coupled with decreased adhesion
      may predict for metastatic potential in vivo.

PMID- 16619500
TI  - Insulin-regulated aminopeptidase/placental leucil Aminopeptidase (IRAP/P-lAP) and
      angiotensin IV-forming activities are modified in serum of rats with breast
      cancer induced by N-methyl-nitrosourea.
AB  - BACKGROUND: In previous reports, changes in oxytocinase activity in human breast
      cancer tissue and in the serum of N-methyl-nitrosourea (NMU)-induced rat mammary
      tumors were described. Insulin-regulated aminopeptidase (IRAP) has been
      identified with oxytocinase and has also been referred to as placental leucine
      aminopeptidase (P-LAP). MATERIALS AND METHODS: The IRAP/P-LAP activity in rat
      serum was assayed to analyze the putative role that IRAP/P-LAP may play in
      regulating mammary gland carcinogenesis induced by NMU. Furthermore, as it has
      been recently described that IRAP/P-LAP is the angiotensin IV (Ang IV) receptor
      AT4, the activities of Ang IV-forming aminopeptidase N (APN) and aminopeptidase B
      (APB) were also assayed. RESULTS: Changes in serum IRAP/P-LAP and Ang IV-forming
      APB activities were found in rats with mammary tumors induced by NMU. Both
      activities were greatly increased, although the Ang IV-forming APN activity was
      not modified. CONCLUSION: These changes in aminopeptidase activities may reflect
      the local functional status of their substrates, which can be selectively
      activated or inhibited in the affected tissue as a result of specific conditions
      brought about by the tumor. Thus, these enzymatic activities may be involved in
      the promotion and progression of breast cancer through oxytocin (OT), vasopressin
      (AVP) and/or renin-angiotensin system (RAS) misregulation.

PMID- 16619501
TI  - Tumour suppressor PTEN regulates cell cycle and protein kinase B/Akt pathway in
      breast cancer cells.
AB  - BACKGROUND: PTEN is a tumour suppressor protein with phosphatase activity
      frequently altered in several types of human cancers. MATERIALS AND METHODS: The
      PTEN effect was studied on the cell cycle (by bromdeoxyuridine incorporation) and
      on the phosphatidylinositol-3-kinase/protein kinase B/Akt (PI3-K/PKB/Akt) pathway
      regulating proteins (by immunocytochemical, Western blot analysis and kinase
      assay) upon transfection of wild-type PTEN and its mutant H123Y in breast cancer
      cell lines. RESULTS: The expression of the important proteins in the MCF-7 and BT
      549 cells was characterised and the cellular localisation of PTEN was analysed.
      Transfection of H123Y led to the down-regulation of p27(Kip1) and p21(Waf1/Cip1)
      protein levels and the up-regulation of phosphorylated PKB/Akt. An overexpression
      of PTEN decreased cyclin E/cdk2 activity and inhibited S-phase entry in MCF-7. In
      BT-549 these changes were not observed, but overexpression of PTEN led to a
      diminution of PKB/Akt phosphorylation. CONCLUSION: PTEN function is mediated
      through the inhibition of the cell cycle and PKB/Akt phosphorylation in breast
      cancer cells.

PMID- 16619502
TI  - Influence of BGP-15, a nicotinic amidoxime derivative, on the vascularization and
      growth of murine hepatoma xenografts.
AB  - BACKGROUND: The expression of vascular endothelial growth factor (VEGF), a key
      regulator of angiogenesis, is controlled by the oxygen supply. Previous
      observations suggested that nicotinic amidoxime derivatives (i.e. BGP-15) might
      interfere with the induction of hypoxia-sensitive genes. Hence, the effect of BGP
      15 on angiogenesis was studied in Hepa 1c1c7 tumor xenografts. MATERIALS AND
      METHODS: Hepa 1c1c7 hepatoma cells were implanted under the dorsal skin of female
      CD-1-nu/nu immunodeficient mice. One group of animals was given 100 mg/kg body
      weight/day BGP-15 intraperitoneally during tumor development. Vascularization,
      apoptotic and mitotic indices were determined by the histological and
      immunohistochemical analysis of the tumors. VEGF and GLUT-1 expressions were
      measured by Northern blot. RESULTS: The in vivo administration of BGP-15 resulted
      in a decrease in tumor weight and mitotic index, while it did not affect the
      apoptotic rate in the xenograft. Furthermore, BGP-15 treatment depressed
      microvascular density and the level of VEGF mRNA by 50%, and similarly decreased
      GLUT-1 mRNA levels. CONCLUSION: These findings suggest that BGP-15 suppresses
      hepatoma development by affecting angiogenesis.

PMID- 16619503
TI  - EGF receptor-related protein (ERRP) inhibits invasion of colon cancer cells and
      tubule formation by endothelial cells in vitro.
AB  - Activation of the epidermal growth factor receptor (EGFR) and/or its family
      member(s) stimulates many processes of carcinogenesis, including cell invasion
      and the formation of new blood vessels, events that are critically involved in
      angiogenesis. Interference with the activation of EGFRs, therefore, represents a
      promising strategy for the development of novel and selective anticancer
      therapies. Previously, we reported that EGFR-related protein (ERRP), which we
      have isolated and characterized as a pan-erbB inhibitor, is a potential
      therapeutic agent for colorectal and other epithelial cancers. The present
      investigation was undertaken to determine whether ERRP would affect the invasion
      of colon cancer cells and formation of tubules, and the regulation of these
      processes. ERRP inhibited tubule formation by aortic endothelial cells and
      invasion of HCT-116 colon cancer cells through matrigel. These changes were
      associated with marked reductions in the synthesis and secretion of bFGF, VEGF
      and TGF-alpha by HCT-116 cells. Secretion of bFGF and VEGF by aortic endothelial
      cells was also inhibited by ERRP. Microarray analysis of ERRP-treated HCT-116
      cells showed reduced levels of several growth regulatory proteins such as
      p21Rac1, Stratifin (14-3-3 Sigma), focal adhesion kinase (FAK) and mediators of
      the Ras-Raf-ERK pathway. ERRP treatments resulted in reduced expression of
      p21Rac1 and inhibited the constitutive activation of FAK and MEK2 in HCT-116
      cells. Transfection of constitutively activate p21Rac1 or MEK2 into HCT-116 cells
      abrogated ERRP-induced inhibition of growth. In summary, it was demonstrated that
      ERRP not only inhibits cell growth, but also the processes of cell invasion and
      blood vessel formation that are critical for the development and progression of
      carcinogenesis.

PMID- 16619504
TI  - Genistein suppresses proliferation and MET oncogene expression and induces EGR-1
      tumor suppressor expression in immortalized human breast epithelial cells.
AB  - Higher soy food intake has been hypothesized to be a major factor explaining the
      decreased breast cancer risk in Asian countries, compared to those regions of the
      world consuming predominantly Western-style diets. Consumption of soy
      isoflavones, particularly genistein, has received considerable attention as the
      soy component largely responsible for the protective effects hypothesized to
      result from soy food consumption. However, the impact of adult consumption of soy
      foods on breast cancer risk in pre-menopausal and menopausal women is not
      consistent. There are recent epidemiological reports that consumption of soy
      foods can most effectively reduce breast cancer risk when consumed early in life
      during the pre-pubertal or adolescent periods. The aim of the present study was
      to evaluate the effects of physiologically-relevant levels of genistein (0.5
      microM and 1 microM), concentrations achievable in the plasma following soy food
      consumption, on proliferation and expression of select genes in the human breast
      epithelial cell model. Treatment of the non-neoplastic, immortalized human breast
      epithelial MCF-10F cells with these low concentrations of genistein was
      associated with decreased cell proliferation, down-regulation of the
      protooncogene MET, up-regulation of the breast tumor suppressor gene EGR-1, and
      up-regulation of the immediate-early response genes FOS and JUN. In addition,
      genistein treatment was associated with a significant increase in Egr-1 binding
      to the transcription factor Sp1. Taken together, these genistein-induced changes
      in gene expressions provide insights into potential mechanisms by which this
      isoflavone may protect human breast cells against neoplastic transformation.

PMID- 16619505
TI  - Efficient delivery of an antisense oligodeoxyribonucleotide formulated in folate
      receptor-targeted liposomes.
AB  - BACKGROUND: Folate receptors (FRs) are cellular surface markers for numerous
      solid tumors and myeloid leukemias. The aim of this study was to develop an
      antisense oligodeoxyribonucleotide (ODN) carrier targeting FR-overexpressing
      cancer cells using folate (FA) as the targeting moiety. G3139, a phosphorothioate
      antisense ODN against human bcl2 mRNA, was evaluated in this study. MATERIALS AND
      METHODS: G3139-containing liposomes were prepared using an ethanol dilution
      method. For the targeted formulation, 0.5 mol% of folate-PEG-DSPE was
      incorporated as a targeting ligand into cationic liposomes composed of DC
      Chol/egg PC/PEG-DSPE at 25:65:10 mol/mol. Particle size and surface charge were
      measured and cellular uptake was assessed by fluorescence microscopy and flow
      cytometry. The ODN-containing formulations were evaluated in FR+ KB cells for
      Bcl2 down-regulation measured by Western blot. The cytotoxicity of the
      formulations was determined by MTT assay. RESULTS: The G3139-containing liposomes
      had an average diameter of 80-90 nm with high ODN entrapment efficiency (70-80%).
      Incorporation of the folate ligand did not significantly alter the particle size
      and entrapment efficiency. The formulation exhibited colloidal stability in a
      serum-containing environment. In uptake studies, the folate-targeted formulation
      showed ligand concentration-dependent uptake that was up to 6-fold more efficient
      than that of the non-targeted formulation (p < 0.05). The uptake could be blocked
      by an excess amount of free folate, thus indicating an FR-dependent mechanism.
      CONCLUSION: FR-targeted G3139-containing liposomes showed promising transfection
      activity in KB cells. FR-targeted formulations were capable of specific targeting
      to FR-overexpressing cell lines and optimizing the amount of folate ligand in the
      liposomal formulation can result in more efficient antisense delivery.

PMID- 16619506
TI  - IgG isotype conversion of a novel human anti-carcinoembryonic antigen antibody to
      increase its biological activity.
AB  - BACKGROUND: The IgG isotype of antibodies is very important for their biological
      functions such as complement-dependent cytotoxicity (CDC) and antibody-dependent
      cellular cytotoxicity (ADCC). To increase the biological activity of a novel
      human monoclonal antibody (C2-45) against carcinoembryonic antigen (CEA), we
      tried to genetically convert its isotype from IgG4 to IgG1. MATERIALS AND
      METHODS: VH and VL genes were cloned from the parental antibody C2-45 (IgG4) and
      inserted into the pAc-kappa-CH3 expression vector which contained the constant
      region gene of human IgG1. The recombinant gene was transfected into Sf9 insect
      cells to produce recombinant protein. The resulting recombinant protein,
      designated C2-45 (cIgG1), in the culture medium was purified by affinity
      chromatography and characterized for its CEA binding activity and biological
      activity. RESULTS: The converted C2-45 (cIgG1) retained the original antigen
      binding activity and showed significantly higher CDC and ADCC activities against
      CEA-expressing tumor cells than did the original C2-45 (IgG4). CONCLUSION: C2-45
      (cIgG1) may be useful for antibody-based immunotherapy of human CEA-expressing
      tumors.

PMID- 16619507
TI  - Paclitaxel toxicity in post-mitotic dorsal root ganglion (DRG) cells.
AB  - Paclitaxel is an antineoplastic drug which acts by enhancing tubulin
      polymerization. The induction of peripheral neuropathy is the main dose-limiting
      side-effect of paclitaxel treatment. In this study, the neurotoxic effect of this
      drug in dorsal root ganglion (DRG) explants was analyzed by measuring the neurite
      length of DRG explants exposed to nerve growth factor (NGF). The neurotoxic
      effect of paclitaxel is dose- and time-dependent. Moreover, in DRG dissociated
      post-mitotic neurons, the molecular and morphological features of paclitaxel
      induced cellular death were studied and the DRG neurons were observed to die by
      necrosis. On the contrary, the proliferating human neuroblastoma SH-SY5Y cells
      exposed to paclitaxel die by apoptosis, as reported for cortical neurons. The
      different response to the same stimulus of different neuronal populations
      underlines the importance of the biochemical and molecular phenotype of the
      neuronal population in determining cellular behavior and vulnerability to the
      same noxious stimulus.

PMID- 16619508
TI  - Minichromosome maintenance protein 7: a reliable tool for glioblastoma
      proliferation index.
AB  - At present there is increasing evidence concerning the value of minichromosome
      maintenance (MCM) protein expression as a novel indicator of proliferation. In
      the present study, 15 glioblastoma samples, classified according to WHO, were
      analysed to evaluate the expression of the principal proliferation markers. The
      samples examined were subdivided into 2 cytological subsets, small cell (SC) or
      multiforme cell (MC) glioblastoma, according to the predominant cell type defined
      in individual specimens. MCM7 detected more cells in the cycle than Ki67 and PCNA
      and all cases of SC glioblastoma, the most aggressive subset, displayed a
      significant increase of MCM7-stained nuclei versus those stained with Ki67. These
      results suggest that the cell cycle-associated proteins MCM are not only useful
      markers of proliferation, but also valid aids for diagnosis in cerebral
      glioblastoma.

PMID- 16619509
TI  - Cancer genetics of sporadic colorectal cancer: BRAF and PI3KCA mutations, their
      impact on signaling and novel targeted therapies.
AB  - Novel activating mutations in sporadic colorectal cancer (CRC) have recently been
      identified on major kinase encoding genes such as BRAF and PI3KCA. The presence
      of these activating point mutations, including the well characterized KRAS
      oncogene mutations, represent up to 75% of cases in CRC. These genes, that have
      been implicated in the adenoma-carcinoma transition, cause deregulation and
      constitutive activation of the MAP AKT/kinase pathways, rendering growth
      advantages to colon tumor cells. This review focuses on the key genetic
      alterations underlying the cumulative effect of multiple mutations within the
      colon cancer cell. Moreover, the currently available and alternative treatment
      approaches that may target these different genetic alterations are discussed,
      such as the novel BRAF inhibitor. Identification of novel mutations as well as
      differential gene expression analyzed by microarray reveal potential targets for
      combined therapeutic protocols which will result in personalized treatments in
      the near future.

PMID- 16619510
TI  - The tyrosine kinase inhibitor AG490 inhibits growth of cancer cells and activates
      ERK in LS174T and HT-29 cells.
AB  - BACKGROUND: The activity of tyrosine kinases, although strictly regulated in
      normal cells, is often disturbed in cancer cells. The inhibition of a tyrosine
      kinase could be a target for treating cancer. MATERIALS AND METHODS: The colon
      cancer cell lines LS174T and HT-29 and the lung cancer cell line NCI-H292 were
      used. The cells were incubated with 100 microM of the tyrosine kinase inhibitor
      AG490 for 1-3 days and were examined for growth. Extracellular signal-regulated
      kinase (ERK) activation was detected by anti-phospho ERK antibodies. The cell
      cycle was analyzed by flow cytometry. RESULTS: AG490 inhibited the growth of
      LS174T, HT-29 and NCI-H292 cells without inducing apoptosis. Short-term treatment
      with AG490 activated ERK and p38 MAPK in the LS174T and HT-29 cells, but not in
      NCI-H292 cells. ERK activation, however, was unrelated to the growth inhibition
      in LS174T cells, because the inhibition persisted even after the prevention of
      ERK activation. CONCLUSION: AG490 inhibits the growth of some cancer cells and
      activates ERK in LS174T and HT-29 cells. ERK activation is unrelated to growth
      inhibition.

PMID- 16619511
TI  - Prestimulation of head and neck cancer cells with growth factors enhances
      treatment efficacy.
AB  - OBJECTIVES: In recent years, new chemotherapy regimens with promising activity,
      especially in first-line therapy (induction chemotherapy) of head and neck cancer
      (SCCHN), have been developed. Nevertheless, a major problem concerning the
      response of SCCHN to chemotherapy is the high percentage of resting cells (G0
      phase cells) being resistant to chemotherapy. To overcome this phenomenon, the
      capacity of several cytokines to switch on cells into the division cycle and
      progress to the chemosensitive phases (S-, M-phases) was investigated. MATERIALS
      AND METHODS: Interleukin-6, serotonin, granulocyte colony stimulating factor (G
      CSF) and epidermal growth factor (EGF) were used to stimulate G0-phase squamous
      cell cancer cells (Detroit 562, A431, UM-SCC 10B) for re-entry into the cell
      cycle to enhance the response to cisplatin. The proportion of G0-phase cells was
      detected through multicolor FACS analysis and Ki-67 staining. RESULTS: Cell cycle
      re-entry was most effective after combination treatment with serotonin + EGF. The
      proportion of G0-phase cells was significantly reduced after stimulation with
      serotonin + EGF (p < 0.05). Corresponding to cell cycle re-entry, the cytotoxic
      effect of cisplatin was significantly (p < 0.04) enhanced in the prestimulated
      compared to the control cells (cisplatin mono-treatment). CONCLUSION: Our
      investigations demonstrated for the first time that sensitizing G0-phase squamous
      cell carcinoma cells for chemotherapy is possible by prestimulation with target
      cytokines. Considering that up to 95% of tumor cells are in the resting (G0)
      phase of the cell cycle at the initiation of chemotherapy, prestimulation with
      EGF and serotonin could contribute to a synchronization of cancer cells. This
      would clearly enhance the cytotoxic effect.

PMID- 16619512
TI  - Down-regulation of cyclin B1 and up-regulation of Wee1 by berberine promotes
      entry of leukemia cells into the G2/M-phase of the cell cycle.
AB  - Berberine has a wide range of biological actions that suggest it may be of use in
      cancer prevention. It was previously reported that berberine induced cell cycle
      arrest, not only at the G0/G1-phase, but also at the G2/M-phase in a dose
      dependent manner. However, the mechanism of berberine-induced G2/M-phase arrest
      in leukemia cells is not fully understood. In the present study, the effects of
      the naturally occurring berberine (the major constituent of Coptis chinensis) on
      the cell cycle, as well as on CDK1, cyclin B1, 14-3-3sigma, Wee1 and Cdc25c
      expressions, were investigated in the human promyelocytic leukemia HL-60 cells
      and in the murine myelomonocytic leukemia WEHI-3 cells. The flow cytometry assays
      indicated that berberine induced G2/M-phase arrest in both examined cell lines.
      The berberine-induced G2/M-phase arrest in both examined cell lines was
      accompanied by increased levels of Wee1 and 14-3-3sigma, but decreased levels of
      Cdc25c, CDK1 and cyclin B1. However, CDK2 expression was not affected as revealed
      by Western blotting assay. Berberine induced G2/M arrest in both the examined
      cells via the inhibition of cyclin B1 and the promotion of Wee1.

PMID- 16619514
TI  - Molecular immunological approaches to biotherapy of human cancers--a review,
      hypothesis and implications.
AB  - The immune system of the human organism comprises the innate system cells and the
      adaptive immune cells. The former include the hematopoietic cells, mast cells,
      basophils, monocytes, dendritic cells (DCs) and macrophages, and the latter
      include CD4+ T cells, CD8+ T cells, T regulatory cells (Tr) and B cells. The
      innate system DCs are the major antigen-presenting cells to Th(o) CD4+ T cells in
      lymph nodes that polarize into T helper 1 (Th1) and T helper 2 (Th2) cells, which
      subsequently produce different cytokines. Polarized Th1 cells produce interleukin
      (IL)-2, IL-12 and interferon (IFN)-gamma, and polarized Th2 cells and the
      hematopoietic cells produce IL-4, IL-5, IL-6, IL-10 and IL-13. In healthy
      individuals there is a Th1/Th2 cytokine balance, but during microbial-induced
      inflammation the pathogens induce an overproduction of the Th2 cytokines that
      inhibit the adaptive immune response against the pathogen. A review of studies on
      the Th1/Th2 cytokine balance in humans harboring different tumor types revealed
      that tumor cells induce increased Th2 cytokine levels in patients' sera that can
      serve as indicators for the existence of tumors. In this review, studies which
      correlated the presence of increased Th2 cytokines with the presence of early
      tumors and tumor progression are discussed. It was suggested that early
      monitoring of human populations for elevated Th2 cytokines may be used to
      identify individuals at an early stage of tumor development. A hypothesis is
      presented which suggests that increased Th2 cytokine synthesis in cancer
      patients, with early and late tumors, may be treated with Th2 cytokine
      antagonists. This new approach to cancer treatment will be supplemented by co
      treatment with CpG oligodeoxynucleotides(ODNs) which reactivate the adaptive
      antitumor immune response. Studies that provide information on the efficiency of
      CpG ODN treatment of tumors in mice revealed that tumor regression was achieved
      by inducing Toll-like receptor 9+ plasmacytoid dendritic cells (PDCs) to release
      large amounts of type I interferons (IFN alpha and beta), which inhibit Th2
      cytokine synthesis by hematopoietic cells and CD4+ T cells and enhance Th1
      cytokine synthesis and activation of the adaptive immunity. It is hypothesized
      that Th2 cytokine (IL-4 and IL-6) antagonists may be an effective treatment for
      cancer patients since cytokine antagonists inhibit the increased Th2 cytokines in
      patients. Such an approach may replace Th2 cytokine monoclonal antibodies, the
      current treatment for cancer patients. It is hypothesized that the effective
      treatment of cancer patients with Th2 cytokine antagonists, combined with CpG
      ODNs, will lead to the inhibition of Th2 cytokines and reacTivation of the Th1
      induced antitumor adaptive immunity that will destroy tumor cells and cure cancer
      patients.

PMID- 16619513
TI  - Ketoprofen-inhibited N-acetyltransferase activity and gene expression in human
      colon tumor cells.
AB  - The activation of ketoprofen, which inhibits the outgrowth of azoxymethane
      induced aberrant crypt foci in the rat colon, on the inhibition of arylamine N
      acetyltransferase (NAT) activity (N-acetylation of substrates), gene expression
      (mRNA NAT) and 2-aminofluorene (AF)-DNA adduct formation was studied in a human
      colon tumor (adenocarcinoma) cell line (colo 205). Cellular cytosols (9000 xg
      supernatant) and intact colon tumor cells were used. The NAT activity in colo 205
      cells was inhibited by ketoprofen in a dose- and time -dependent manner in both
      examined systems. The data also indicated that ketoprofen decreased the apparent
      value of V(max) of NAT enzymes, being a competitive inhibitor of NAT enzymes. The
      AF-DNA adduct formation in colo 205 cells was also decreased by ketoprofen. Based
      on the results from PCR, it was shown that ketoprofen affected mRNA NAT
      expression in human colon colo 205 cells. The cells were stained with anti-NAT
      antibody, then analyzed by flow cytometry. The results showed that ketoprofen
      decreased the percentage of cells stained by anti-NAT. This report is the first
      to demonstrate that ketoprofen inhibits human colon tumor cell NAT activity, gene
      expression and DNA adduct formation.

PMID- 16619515
TI  - Antitumor properties and toxicity of dextran-methotrexate conjugates are
      dependent on the molecular weight of the carrier.
AB  - Methotrexate (MTX) is widely utilized in the clinical treatment of many forms of
      cancer. However, the drug has a short plasma half-life and causes toxic effects
      on normal proliferating cells. Conjugation with carriers is a possible way to
      alter these disadvantageous pharmacokinetics. Our aim was to synthesize dextran
      MTX (D-MTX) conjugates, using carriers with molecular weights (Mw) ranging from
      10 kDa to 500 kDa. Their in vitro and in vivo properties were compared with free
      MTX. The in vitro studies revealed that D-MTX conjugates had 4- to 10-fold lower
      antiproliferative effects against neoplastic cell lines compared to free MTX.
      There was a negative relationship between the Mw of the carrier and the
      antiproliferative effect of the respective conjugate. The data obtained in a
      mouse leukemia P388 in vivo model suggested that a lower in vitro
      antiproliferative effect of the conjugates does not result in diminished
      antileukemic activity in vivo. The toxicity of the conjugates was greater in
      comparison with the parent drug and tended to rise with increasing Mw. However,
      no superiority over free MTX in terms of an antileukemic effect was demonstrated.
      In particular, the D-MTX conjugate based on the dextran with Mw 10 kDa showed a
      comparable antileukemic effect with an even lower toxicity than that of free MTX.
      The data suggest that at least the toxicity of conjugates is dependent on the Mw
      of the carrier. This fact should be taken into account when designing new
      anticancer polymer-drug compounds.

PMID- 16619516
TI  - Combination effect of TZT-1027 (Soblidotin) with other anticancer drugs.
AB  - BACKGROUND: TZT-1027 (Soblidotin), an antimicrotubule drug, has shown potent
      antitumor efficacy in various antitumor models, and has entered into phase I
      clinical trials. To determine those anticancer drugs to be combined with TZT-1027
      in clinical trials, the combination effects of TZT-1027 with other anticancer
      drugs were examined. MATERIALS AND METHODS: Two in vivo antitumor models, the
      murine P388 leukemia ascites tumor model and the human non-small cell lung cancer
      A549 solid tumor model, were used and cisplatin (CDDP), gemcitabine (GEM),
      irinotecan hydrochloride (CPT-11), fluorouracil (5-FU), paclitaxel (PTX) and
      docetaxel (DTX) were selected to be combined with TZT-1027. Regarding the
      schedule of combination administration, simultaneous administration and
      sequential administration (TZT-1027 first and combined drugs administered 24 h
      later, and vice versa) were employed. RESULTS: A significant increase in lifespan
      was observed when TZT-1027 was combined with CDDP, GEM and CPT-11 in the P388
      cell ascites tumor model, and a significant inhibition of growth was observed
      when TZT-1027 was combined with CDDP, GEM and DTX in the A549 solid tumor model.
      Sequential administration, particularly when the combined drug was administered
      first, showed the most potent antitumor efficacy. CONCLUSION: These findings
      strongly suggest that a significant combination effect of TZT-1027 and these
      antitumor drugs can be expected in clinical trials for solid tumors.

PMID- 16619517
TI  - C-jun N-terminal kinase activation is required for apoptotic cell death induced
      by TNF-related apoptosis-inducing ligand plus DNA-damaging agents in sarcoma cell
      lines.
AB  - BACKGROUND: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)
      in combination with a chemotherapeutic agent, cis-diammine dichloroplatinum
      (CDDP) or doxorubicin (DXR), has recently been demonstrated to result in enhanced
      apoptotic cell death in the sarcoma cell lines MG-63 and SaOS-2. DNA-damaging
      agents, such as CDDP induced sustained activation of c-Jun N-terminal kinase
      (JNK), probably leading to apoptosis. In the present study, whether JNK
      activation is involved in apoptotic cell death induced by combined treatment with
      CDDP/DXR and TRAIL was addressed. RESULTS: MG-63 or SaOS-2 cells overexpressing
      the dominant-negative (dn) form of JNK (dnJNK1) were established by transfection
      with dnJNK1 cDNA. Following stimulation with the chemotherapeutic agent CDDP or
      TRAIL, both MG-63 and SaOS-2 cells demonstrated enhanced cell death compared with
      stimulation by either agent alone, as assayed for apoptosis using annexin V
      staining or mitochondrial membrane potential using DiOC6 staining. Interestingly,
      partial inhibition of the cell death induced by the combined treatment with
      CDDP/DXR and TRAIL was found in MG-63 or SaOS-2 cells overexpressing dnJNK1,
      suggesting that JNK activation is required for the combined treatment. Moreover,
      induction of caspase-8 activation by TRAIL or TRAIL plus CDDP/DXR was
      substantially prevented by dnJNK. CONCLUSION: Efficient cell death induced by
      combined treatment with the chemotherapeutic agents CDDP/DXR and TRAIL is
      involved in JNK activation in the sarcoma cell lines MG-63 and SaOS-2. These
      results would be useful for treatment modalities of patients with sarcoma.

PMID- 16619518
TI  - Is aneusomy of chromosome 9 alone a valid biomarker for urinary bladder cancer
      screening?
AB  - BACKGROUND: Detection of genetically-changed tumor cells in the urine is one of
      the new approaches for the screening of bladder carcinomas. In a previous study,
      numerical aberrations of chromosome 9 were found in 85.18% of bladder tumors
      studied by the fluorescence in situ hybridization (FISH) technique. The purpose
      of the present study was to investigate whether chromosome 9 aneusomy alone is a
      valid, cost effective, biomarker for bladder cancer screening. MATERIALS AND
      METHODS: Twenty-seven voided urine specimens obtained from 22 bladder cancer
      patients, either at initial diagnosis or at the follow-up, were analyzed by the
      FISH technique with the centromeric probe specific for chromosome 9. RESULTS: In
      all except 2 out of the 13 specimens with a histological confirmation of cancer,
      FISH analysis showed aneusomy 9 (sensitivity 84.61%). Among 6 cases with a
      negative cystoscopy but a positive FISH analysis, 3 recurred within the following
      2 months, while 2 no-recurrent patients continued to show positive FISH findings
      after 6 months. One patient was considered to be false-positive. Four cases with
      a negative cystoscopy showed disomy 9 and 2 of them recurred. CONCLUSION:
      Aneusomy 9 has a high sensitivity (84.61%) for the detection of bladder cancer.
      Patients with a negative cystoscopy but with aneusomy 9 should be kept under
      close clinical surveillance for potential disease recurrence. However, negative
      FISH results might not be a negative predictor for disease recurrence. Our
      results encourage further studies with a large number of patients and a long-term
      follow-up with concurrent FISH analysis.

PMID- 16619519
TI  - Absence of L1 in pancreatic masses distinguishes adenocarcinomas from poorly
      differentiated neuroendocrine carcinomas.
AB  - BACKGROUND: Pancreatic adenocarcinoma is a tumor with fatal outcome. Cell
      adhesion molecules, such as L1 (CD171), have an essential function in tumor
      progression. L1 has been shown to be specifically expressed in poorly
      differentiated neuroendocrine carcinomas of the pancreas. The aim of this study
      was to determine the expression of L1 in pancreatic adenocarcinomas to evaluate
      whether L1 might differentiate between pancreatic carcinomas of neuroendocrine
      and ductal origin. MATERIALS AND METHODS: L1 expression was retrospectively
      analyzed in 111 cases of pancreatic adenocarcinomas by immunohistochemistry on
      paraffin sections of primary tumors. Staining was performed by the peroxidase
      technique with monoclonal antibody against human L1. All tumors were classified
      according to the most recent TNM classification. RESULTS: The focal expression of
      L1 was detected in 2 (2%) out of 111 pancreatic carcinomas only, the remaining
      109 (98%) being L1-negative. No expression was found in acinar or ductal cells of
      normal pancreatic tissue. CONCLUSION: Our data suggest that L1 is expressed in
      few cases of pancreatic ductal adenocarcinoma. Since L1 was previously found to
      be expressed specifically in neuroendocrine pancreatic carcinomas, its absence in
      unclear pancreatic masses might hint at a ductal origin for a malignant
      pancreatic tumor.

PMID- 16619520
TI  - Antisense p53 oligonucleotides inhibit proliferation and induce chemosensitivity
      in follicular thyroid cancer cells.
AB  - BACKGROUND: The potential of MTp53 knockout by oligodesoxyribonucleotide
      phosphothioates (ODNs) to affect proliferation, apoptosis and chemosensitivity in
      undifferentiated thyroid cancer (UTC) cells with a recessive MTp53 mutation was
      evaluated. MATERIALS AND METHODS: Transient transfections with ODNs complementary
      to p53 and control ODN (HIV-RT) were carried out in FTC 133 cells. In vitro
      proliferation was evaluated by cell counting of 10 random fields and by the MTT
      assay. A single pulse of 100 microg/ml Cytarabine was added to each well and the
      cells were incubated for an additional day. Chemosensitivity was calculated as
      the ratio of apoptotic and necrotic cells versus viable cells by flow cytometry
      (FACS). RESULTS: Transfection of UTC cells with ODN decreased the cell number by
      up to 70% (p < 0.002). The proliferation rate also decreased up to 35% (p <
      0.03), without inducing apoptosis. ODNs rendered FTC cells sensitive to treatment
      with Cytarabine, inducing apoptosis in 35% of cells, as compared to 17% of cells
      transfected with the reverse transcriptase gene of HIV (ODN-HIV) and less than
      10% of non-transfected cells (p < 0.05). CONCLUSION: Transient MTp53 knockout
      with ODNs complementary to p53 nucleotide sequences inhibited proliferation and
      increased chemosensitivity in the UTC cell line FTC133.

PMID- 16619521
TI  - The antiproliferative effect of Quercetin in cancer cells is mediated via
      inhibition of the PI3K-Akt/PKB pathway.
AB  - BACKGROUND: The tumor suppressor gene PTEN, mutated in 40-50% of patients with
      brain tumors, especially those with glioblastomas, maps to chromosome 10q23.3 and
      encodes a dual-specificity phosphatase. PTEN exerts its effects partly via
      inhibition of protein tyrosine kinase B (Akt/Protein Kinase B), which is involved
      in the phosphatidylinositol (PtdIns) 3-kinase (PI3K)-mediated cell-survival
      pathway. The naturally occurring bioflavonoid Quercetin (Qu) shares structural
      homology with the commercially available selective PI3K inhibitor, LY 294002
      (LY). Here, the effects of Qu on the Akt/PKB pathway were evaluated. MATERIALS
      AND METHODS: The human breast carcinoma cell lines, HCC1937, with homozygous
      deletion of the PTEN gene, and T47D, with intact PTEN, were time-treated with Qu
      or LY and analyzed for activated levels of Akt by measuring phospho-Akt (p-Akt)
      levels using immunoblotting analysis. To detect p-Akt, the T47D cells were
      treated with EGF prior to treatment with or without Qu or LY Cell proliferation
      after 24-h treatment with Qu or LY was quantified by the 3-(4, 5-dimethylthiazol
      2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Treatment with Qu
      (25 microM) for 0.5, 1 and 3 h completely suppressed constitutively activated
      Akt/PKB phosphorylation at Ser-473 in HCC1937 cells. Pre-exposing T47D cells to
      Qu (25 microM) or LY (10 microM) abrogated EGF-induced Akt/PKB phosphorylation at
      Ser-473. Both Qu (100 microM) and LY (50 microM) treatments for 24 h
      significantly decreased cell proliferation, as shown by the MTT assay.
      CONCLUSION: Pharmacologically safe doses of the naturally occurring bioflavonoid
      Qu inhibit the PI3K-Akt/PKB pathway, in a manner similar to that of the
      commercially available LY. Overall, our results indicated that Qu inhibited the
      constitutively activated-Akt/PKB pathway in PTEN-null cancer cells, and suggest
      that this compound may have therapeutic benefit against tumorigenesis and cancer
      progression.

PMID- 16619522
TI  - Evaluation of adaptive responses to cisplatin in normal and mutant cell lines
      with mutations in recombination repair pathways.
AB  - Cell lines mutant in specific DNA repair pathways were used to determine if these
      pathways are involved in adaptive responses. For these studies, the effect of
      deficiencies in homologous recombination repair (HR) were studied in the parental
      AA8 and mutant (irs)ISF cell line pair and for deficiencies in the nonhomologous
      endjoining (NHEJ) pathway in the mouse MEF parental and Ku80 mutant cell line
      pair. The results showed that the XRCC3 mutation in the HR-deficient mutant
      inhibited adaptive responses to low doses of cisplatin and radiation. The
      parental lines showed transient adaptive responses to both low-dose cisplatin and
      radiation treatment. For the mouse MEF and the Ku80 cells, no adaptive responses
      were observed in either cell line. However, there was an initial transient
      sensitization response followed by partial recovery. Thus, it appears that the HR
      repair system may be involved in the adaptive response to cisplatin and
      radiation. For the NHEJ repair system the question could not be answered since no
      adaptive responses were evident in the parental line.

PMID- 16619523
TI  - Behavioral stress and tumor progression.
AB  - BACKGROUND: A number of laboratories have reported a possible link between
      behavioral stress and cancer progression. Previously published findings
      demonstrated a stress-induced increase in tumor growth of implanted lymphosarcoma
      in C3H mice. Here, two mouse models were utilized to investigate whether stress
      alters the growth of solid tumors. MATERIALS AND METHODS: We developed a stress
      paradigm that involves alternating established stressors for 12 days. FVB mice
      implanted with melanoma were subjected to this stress protocol. We also attempted
      to duplicate Riley's finding. RESULTS: Our stress paradigm markedly increased
      serum corticosterone levels and thymus involution. No alteration in the growth of
      the melanoma tumors was observed. There was also no significant effect on
      lymphosarcoma progression using either our own or Riley's stress protocol.
      CONCLUSION: Under the conditions used in this study, strong behavioral stress did
      not influence tumor progression.

PMID- 16619524
TI  - Array-based genomic analysis of screen-detected Gleason score 6 and 7 prostatic
      adenocarcinomas.
AB  - BACKGROUND: Prostate cancer is known for its heterogeneous histological
      appearance. It is currently not clear whether this histological heterogeneity is
      also reflected in the genomic composition of a tumor. MATERIALS AND METHODS: The
      cancer DNA's were retrieved from the European Randomized Study of Screening for
      Prostate Cancer section Rotterdam (ERSPC). Tumors with volumes 1.0-1.5 ml and a
      Gleason score of 3+3 or 3+4 were selected. Comparative genomic hybridization with
      a 3500-element BAC array was used to detect differences in the genetic content of
      Gleason patterns 3 and 4. RESULTS: A total of 1155 gains and 583 losses were
      discriminated in 10 G3 areas; 768 gains and 497 losses were detected in 7 G4
      regions. Frequent losses included chromosome arms 6q, 8p and 13q, while frequent
      gains were seen on 7q and 8q. There were no significant differences between
      Gleason patterns 3 and 4, or between Gleason grades within one cancer.
      CONCLUSION: Histological heterogeneity, defined by Gleason grades 3 and 4, does
      not have a genomic counterpart. Furthermore, these asymptomatic screen-detected
      prostate carcinomas have genetic signatures comparable with those commonly seen
      in symptomatic cancers.

PMID- 16619525
TI  - FLT3 overexpression in acute promyelocytic leukemia patients without detectable
      FLT3-ITD or codon 835-836 mutations: a pilot study.
AB  - BACKGROUND: Activating mutations of the FLT3 receptor tyrosine kinase are common
      in acute promyelocytic leukemia (APL) but have uncertain prognostic significance.
      Information regarding FLT3 expression levels in APL without FLT3 mutations is
      lacking. MATERIALS AND METHODS: Using RT-PCR, mutation analysis of the FLT3 gene,
      regarding internal tandem duplications (ITDs) and codon 835-836 point mutations,
      was performed and real-time PCR was carried out to determine the level of FLT3
      expression in 11 APL patients at diagnosis and 5 in haematological remission with
      molecularly detectable disease. RESULTS: High levels of FLT3 transcript, at least
      a 10-fold increase compared to the normal controls, were found at diagnosis in
      all 3 mutated cases and in 2 patients without detectable FLT3 mutations.
      CONCLUSION: FLT3 overexpression can be documented in patients without FLT3
      mutations. These patients might benefit from treatment using specific FLT3
      tyrosine kinase inhibitors. Larger studies are needed to evaluate the clinical
      and biological significance of FLT3 overexpression in the absence of FLT3
      mutations.

PMID- 16619526
TI  - TNF-alpha production-enhancing activity of 2-(1-adamantylamino)-6-methylpyridine
      (AdAMP) in cultures of human normal and neoplastic cells.
AB  - The purpose of this study was to determine the TNF-alpha-stimulatory effect of a
      novel immunomodulator 2-(1-adamantylamino)-6-methylpyridine (AdAMP) on normal and
      neoplastic human cells. In a panel of several human ovarian cancer cell lines,
      almost half of them spontaneously secreted significant amounts of TNF-alpha. When
      incubated with AdAMP, a 3-fold enhancement of TNF-alpha production by cells was
      observed. Furthermore, the phorbol myristic acetate ester (PMA)-induced release
      of TNF-alpha in cultures of U937 cells was increased in the presence of AdAMP.
      Primary monocytes isolated from peripheral blood did not respond to AdAMP.
      Although cytokine release was not triggered in human peripheral blood monocytes,
      AdAMP co-stimulated these cells to produce TNF-alpha and IL-8 during incubation
      with lipopolysaccharide (LPS). No effect of AdAMP was found on IL-1beta and IL-6
      production by monocytes. In cultures of peripheral blood T lymphocytes, AdAMP
      significantly decreased the adhesion of these cells to matrix proteins in an in
      vitro assay. The results suggest that AdAMP, as a stimulator of cytokine
      secretion, may have potential application in tumor therapy.

PMID- 16619527
TI  - Radio-iodination of monoclonal antibody using potassium [125I]-(4
      isothiocyanatobenzylammonio)-iodo-decahydro-closo-dodecaborate (iodo-DABI).
AB  - BACKGROUND: Negatively-charged polyhedral boron clusters can be easily
      halogenated with highly stable boron-halogen bonds and are promising in
      radionuclide diagnostics and cancer therapy. MATERIALS AND METHODS: The radio
      iodination conditions for the closo-dodecaborate anion and for the conjugation of
      its labeled isothiocyanatobenzylammonio derivative to the monoclonal antibody
      (mAb) were optimized. RESULTS: The labeling yield was about 90% and the overall
      conjugation yield was 55-60%. The in vitro stability of the radio-iodinated mAb
      was good under physiological and non-physiological conditions. The
      immunoreactivity of the labeled mAb (SK-BR-3 cells) was retained in the one-pot
      two-step labeling. CONCLUSION: Negatively-charged polyhedral boron clusters can
      be used for indirect radio-iodination of mAbs.

PMID- 16619528
TI  - Epigenetic mechanism of growth inhibition induced by phenylhexyl isothiocyanate
      in prostate cancer cells.
AB  - BACKGROUND: Isothiocyanates, the constituents of cruciferous vegetables, may be
      able to prevent prostate cancer. The hypothesis that they could remodel
      chromatins and activate cell cycle inhibitors, such as p21 for growth inhibition,
      was tested. MATERIALS AND METHODS: Prostate cancer LNCaP cells were exposed to
      phenylhexyl isothiocyanate (PHI). The status of histone acetylation and the
      activity of histone deacetylases (HDAC) were investigated. The association of p21
      with hyperacetylated histones was examined by chromatin immunoprecipitation.
      RESULTS: The PHI-exposed LNCaP cells had diminished activity of HDAC 1 and 2.
      Global and selective histone acetylation was enhanced, consistent with the signs
      of chromatin unfolding. The hyperacetylated histones increased accessibility to
      the p21 promoter for transcription, leading to G1 arrest and apoptosis.
      CONCLUSION: PHI inhibited the activity of HDAC and remodeled chromatins to
      activate p21 for cell cycle arrest, underlying an epigenetic mechanism regulating
      the growth of prostate cancer cells.

PMID- 16619529
TI  - Exonic deletions of mismatch repair genes MLH1 and MSH2 correlate with prognosis
      and protein expression levels in malignant melanomas.
AB  - The mutations of MLH1 and MSH2 have been reported to be responsible for malignant
      transformation and tumour progression in several sporadic tumours. Eighty-six
      primary malignant melanomas with known follow-up were investigated. Point
      mutations of DNA mismatch repair MLH1 and MSH2 in malignant melanomas were not
      found. Exon 12 (MSH2) was not present in 26 out of the 86 melanomas and exon 13
      (MSH2) was lost in 25 of the tumours. The loss of exon 15 (MLH1) was observed in
      22 out of the 86 tumours and the loss of exon 16 (MLH1) in 24 melanomas. The loss
      of exons correlated strongly with the loss of MLH1 and MSH2 protein expression.
      In multivariate analysis, including all 4 exons and expressions of MLH1 and MSH2,
      prognostic significance was found only for loss of exon 12 (MSH2) and loss of
      exon 15 (MLH1).

PMID- 16619530
TI  - Resveratrol suppresses angiogenesis in gliomas: evaluation by color Doppler
      ultrasound.
AB  - BACKGROUND: The effects of resveratrol (a natural polyphenol) on angiogenesis in
      rat gliomas were investigated by color Doppler ultrasound (CDUS). The correlation
      among the tumor growth rate, macroscopic angiogenesis measured by CDUS and
      microscopic angiogenesis was assessed by immunohistochemical staining. MATERIALS
      AND METHODS: Fischer rats were subcutaneously inoculated with rat RT-2 glioma
      cells and treated with resveratrol for 4 weeks. The tumor size was measured and
      the animal survival followed. CDUS examination was used to measure tumor blood
      flow shown as the color Doppler vascularity index (CDVI). Immunohistochemical
      staining of CD31 was carried out to assess the microvessel density (MVD) of the
      tumors. The CDVI, MVD and tumor size were correlated. RESULTS: Rats treated with
      resveratrol (40 mg/kg/day) had slower tumor growth rates than those of the
      control groups (p < 0.05). The CDVI, MVD and tumor size were significantly
      correlated (linear regression, p < 0.0001). CONCLUSION: Resveratrol-suppressed
      glioma growth was significantly correlated with the inhibition of macroscopic and
      microscopic angiogenesis.

PMID- 16619531
TI  - Establishment of a mouse gastrointestinal stromal tumour model and evaluation of
      response to imatinib by small animal positron emission tomography.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GIST) predominantly express
      activating mutations of the KIT tyrosine kinase receptor and are successfully
      treated with imatinib mesylate, a KIT inhibitor. As resistance to imatinib causes
      therapy failure, our aim was to develop an in vivo GIST model to evaluate KIT
      inhibitors and monitor therapy with small animal positron emission tomography
      (PET). MATERIALS AND METHODS: The first mouse model of GIST xenografts was
      successfully established by injecting GIST882 cells subcutaneously into nude
      mice. RESULTS: Using the small animal PET, FDG up-take in xenografts was
      significantly decreased after 24 h of treatment with imatinib, which correlated
      with a response to treatment, e.g., with a decrease in tumour volume, the
      inhibition of KIT and downstream intermediate phosphorylation and arrest of
      tumour cell proliferation as evaluated after 7 days of treatment. CONCLUSION:
      This model is useful to study imatinib resistance and to evaluate novel targeted
      therapies.

PMID- 16619532
TI  - Significance of pituitary tumor transforming gene 1 (PTTG1) in prostate cancer.
AB  - Recently, the pituitary tumor transforming gene 1 (PTTG1) has been suggested to
      be an oncogene. To investigate whether PTTG1 plays a positive role in the
      pathogenesis of prostate cancer, PTTG1 protein expression was examined in
      prostate tissue samples by immunohistochemistry. PTTG1 expression was detected in
      a high percentage of prostate cancer tissues (34/41, 82.9%), but to a much lesser
      extent in non-malignant tissues (5/14, 35.7%). To further confirm these results,
      the expression vectors containing either the PTTG1 or antisense-PTTG1 gene were
      transfected into a prostate cancer cell line, LNCaP, and the cell proliferation
      rate was studied, as well as tumorigenicity in the LNCaP cells expressing
      different levels of the PTTG1 protein. Ectopic PTTG1 gene expression promoted
      prostate cancer cell proliferation and tumorigenesis both in vitro and in nude
      mice. In contrast, down-regulation of PTTG1 led to suppression of tumor cell
      growth. These results suggest that PTTG1 may be a potential prognostic marker for
      prostate cancer and that the down-regulation of PTTG1 may be a therapeutic target
      in the suppression of prostate cancer growth.

PMID- 16619533
TI  - Evaluation of hypoxic cell radio-sensitizers in terms of radio-sensitizing and
      repair-inhibiting potential. Dependency on p53 status of tumor cells and the
      effects on intratumor quiescent cells.
AB  - BACKGROUND: Intratumor quiescent (Q) cells and p53-mutated tumor cells are more
      difficult to control than intratumor proliferating (P) cells and p53 wild-type
      tumor cells, respectively. The usefulness of 3 hypoxic cell radio-sensitizers was
      compared in terms of a radio-sensitizing effect under aerobic and hypoxic
      conditions and a repair-inhibiting effect following irradiation on both Q and
      total (P + Q) cell populations in solid tumors. The dependency of these effects
      on the p53 status of tumor cells was also examined using tumor cell lines with
      identical genetic backgrounds except for their p53 status. MATERIALS AND METHODS:
      Human head and neck squamous cell carcinoma cells transfected with mutant TP53
      (SAS/mp53) or with neo vector as a control (SAS/neo) were inoculated
      subcutaneously into both the hind legs of Balb/cA nude mice. The nude mice
      bearing the tumors and C3H/He mice bearing SCC VII tumors received 5-bromo-2'
      deoxyuridine (BrdU) continuously to label all the P cells in the tumors. Tumor
      bearing mice received gamma-ray irradiation while alive or following tumor
      clamping after being administered no drug, nimorazole, SR-2514 or misonidazole,
      or received no drug, nimorazole, SR-2514 or misonidazole straight after gamma-ray
      irradiation. For the group irradiated after receiving the drug, the tumors were
      excised immediately following irradiation, while for the group irradiated before
      receiving the drug, the tumors were excised 24 h after irradiation. The excised
      tumors were minced and trypsinized. The tumor cell suspensions thus obtained were
      incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN)
      frequency in the cells without BrdU labelling (= quiescent (Q) cells) was
      determined using immunofluorescence staining for BrdU. Meanwhile, the MN
      frequency in the total tumor cell population was determined from the tumors that
      had not been pretreated with BrdU. The clonogenic cell survival was also
      determined in the mice given no BrdU. RESULTS: Both the radio-sensitizing effects
      under aerobic and hypoxic conditions and the repair-inhibiting effects following
      gamma-ray irradiation increased in the following order: nimorazole < SR-2514 <
      misonidazole in both total and Q cells in these 3 tumors. Both effects were more
      marked in the Q cells and p53-mutated tumors than in the total cells and p53-wild
      tumors, respectively. CONCLUSION: In terms of controlling radio-resistant Q tumor
      cells and p53-mutated tumor cells, the combination of radio-sensitizers and
      conventional radiotherapy is promising both for radio-sensitization and for
      repair-inhibition, but further study of the toxicity to normal tissues is needed.

PMID- 16619534
TI  - Celecoxib induces regression of putative preneoplastic lesions in rat liver.
AB  - BACKGROUND: Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, may reduce the risk
      and mortality of certain types of human cancer. The chemopreventive effect of
      celecoxib on preneoplastic lesions induced by chemical hepatocarcinogenesis was
      investigated. MATERIALS AND METHODS: Male Sprague Dawley rats were fed a
      celecoxib-supplemented diet between days 18 and 26 post-initiation (1500 ppm) and
      sacrificed on day 26. The effects of celecoxib on proliferation, apoptosis, COX-2
      activity and liver function were evaluated by immunohistochemistry, TUNEL assay,
      enzyme-immunoassay and spectrophotometry, respectively. RESULTS: Celecoxib
      decreased, in area and number, gamma-glutamyltranspeptidase and glutathione S
      transferase placental-positive lesions, below levels found after 18 days, by
      55.2% and 62.2%, and by 50.5% and 71.1%, respectively, (p < 0.05). Celecoxib
      neither induced apoptosis nor altered the levels of prostaglandin E2, bilirubin
      or alanine aminotransferase in the plasma; however, proliferating cell nuclear
      antigen and cyclin D1 decreased by 77.7% and 94.9%, respectively, (p < 0.05).
      CONCLUSION: Celecoxib regresses existing preneoplastic liver lesions through
      antiproliferative processes, without altering liver function.

PMID- 16619535
TI  - Curcumin inhibits cell migration of human colon cancer colo 205 cells through the
      inhibition of nuclear factor kappa B /p65 and down-regulates cyclooxygenase-2 and
      matrix metalloproteinase-2 expressions.
AB  - Curcumin (diferuloylmethane) is a chemical derived from several Curcuma species
      (turmeric), possessing anti-inflammatory and antioxidant properties and which,
      thus, may be a potential anticancer drug. However, its mechanism of action is not
      fully understood. Our previous studies had shown that curcumin induced
      cytotoxicity, cell cycle arrest and apoptosis in human colon cancer colo 205
      cells. In this study, curcumin affected the levels of NF-kappaB/ p65 in a time
      dependent manner but did not affect NF-kappaB/ p50, based on Western blotting
      methods. In vitro experiments revealed that curcumin inhibited Cox-2 levels, but
      promoted those of Cox-1 in colo 205 cells. Curcumin also inhibited MMP-2 levels
      and promoted MMP-9 levels, but did not affect MMP-7 levels, based on Western
      blotting assays. These effects were also confirmed by cDNA microarray.
      Remarkably, curcumin not only exerted its effect on the protein levels of NF
      kappaB, Cox-1 and -2, MMP-2 and -7, but also directly inhibited their mRNA
      levels. Curcumin was also found to significantly repress the in vitro invasion of
      colo 205 cells.

PMID- 16619536
TI  - Effects of PRIMA-1 on wild-type L1210 cells expressing mutant p53 and drug
      resistant L1210 cells lacking expression of p53: necrosis vs. apoptosis.
AB  - The effects of PRIMA-1 on wild-type (WT) mouse leukemia L1210 cells and drug
      resistant L1210 cells (Y8) were studied with respect to the induction of
      apoptosis and necrosis in these cell lines. The WT L1210 cells express mutant p53
      while the Y8 L1210 cells do not express p53 mRNA or protein, but do express
      WAF1/p21 and Gadd 45 mRNA's and proteins. It was found that, in response to
      treatment with PRIMA-1, the WT L1210 cells became necrotic with little apoptosis
      while the Y8 L1210 cells showed a much higher level of apoptosis than necrosis.
      Flavopiridol in combination with PRIMA-1 caused a synergistic increase in
      necrosis in the WT L1210 cells while LY 294002 in combination with PRIMA-1 caused
      a synergistic increase in apoptosis in the Y8 L1210 cells. These studies showed
      that PRIMA-1 had an effect not only on cells expressing mutant p53, but also on
      cells that do not express p53, suggesting that PRIMA-1 and PRIMA-1-like molecules
      have multiple sites of action independent of restoring p53 function and that
      these can interact with other signaling pathways involving CDK's and PI3 kinases.

PMID- 16619538
TI  - PCNA-LII, Ki-67 immunostaining, p53 activity and histopathological variables in
      predicting the clinical outcome in patients with parathyroid carcinoma.
AB  - Parathyroid carcinoma is uncommon and no reliable histological markers are
      available for predicting the clinical outcome of patients. The aim of this study
      was to assess the correlation between survival, histopatological markers,
      proliferating cell nuclear antigen (PCNA), Ki-67 antigen and the expression of
      the p53 nuclear protein in patients with confirmed parathyroid carcinoma (PC).
      The routine histological specimens from 15 patients (11 men, 4-women, median age
      65 years) with confirmed PC who had died of the disease were reviewed. New
      specimens were also stained with the streptavidin-biotin-peroxidase complex
      standard technique. The labelling index (LI) of PCNA was quantified by counting
      1000 cells from multiple areas in a random fashion, while immunostaining of both
      Ki-67 and p53 was evaluated as the percentage of positive cells. The PCNA-LI, Ki
      67 (%) and p53 (%) values were 14.9 +/- 4.1 (median 13, range 2-70), 13.9 +/- 3.9
      (median 11%, range 3-65%) and 38.5 +/- 4.6 (median 29%, range 19-65%),
      respectively. There was an inverse correlation between age of the patients and
      p53 (R = -0.73, p = 0.002), but no correlation with both PCNA-LI (R = 0.07, p =
      0.72) and Ki-67 (R = -0.07, p = 0.79). A significant relationship (R = 0.93, p <
      0.01) between PCNA-LI and Ki-67 was found, while p53 did not correlate with
      either PCNA-LI (R = -0.11, p = 0.71) or Ki-67 (R = -0.05, p = 0.86). An inverse
      correlation (R = -0.63, p = 0.01) between survival and the presence of spindle
      cells and coagulation necrosis together in the standard slides was observed, but
      there was no correlation (p = NS) between survival and PCNA-LI (R = 0.05), Ki -67
      (R = 0.05) or p53 (R = 0.25). In conclusion, none of the tested
      immunohistochemical markers were useful in predicting the clinical outcome of
      patients with PC. However, the presence of spindle cells and coagulation necrosis
      together in the standard specimens should be considered as a negative prognostic
      factor.

PMID- 16619537
TI  - Role of mitochondria in quercetin-enhanced chemotherapeutic response in human non
      small cell lung carcinoma H-520 cells.
AB  - Dietary phytochemicals have been shown to be chemopreventive against various
      types of cancer. This study was designed to investigate the enhancement of the
      chemoresponse to cisplatin by quercetin in human lung cancer H-520 cells and to
      elucidate the role of mitochondria in the induction of apoptosis. Apoptosis was
      detected by flow cytometry. The protein expressions of Bcl-XL, Bcl-2, Bax,
      cytochrome c and AIF were studied by Western blotting. The transcription of
      antioxidant enzymes was quantitated by RT-PCR. The findings suggested that
      priming H-520 cells with quercetin increased the cisplatin-induced apoptosis by
      30.2%. This was accompanied by down-regulation of Bcl-XL and Bcl-2 and up
      regulation of Bax. Both cytochrome c and AIF were implicated in the apoptotic
      process. There was no significant change in the transcription level of
      antioxidant enzymes in quercetin-mediated apoptosis. Based on these findings, it
      can be concluded that quercetin might act as an effective chemosensitizer in the
      chemotherapy of lung cancer by regulating the expression of various apoptosis
      related genes.

PMID- 16619539
TI  - A related donor and reduced intensity conditioning reduces the risk of
      development of BK virus-positive haemorrhagic cystitis in allogeneic
      haematopoetic stem cell-transplanted patients.
AB  - The significance of the BK virus (BKV) and possible co-factors for the
      development of late onset haemorrhagic cystitis (HC) in allogeneic haematopoetic
      stem cell (HSCT)-transplanted patients is reviewed. BKV-associated HC causes
      significant morbidity and mortality in HSCT patients, however, BK-viruria cannot
      distinguish patients at risk of HC, since it is observed in patients with and
      without HC. Several studies have therefore attempted to identify co-factors for
      the development of HC. Acute graft versus host disease was in the past, though
      less so recently, reported to correlate to the incidence of HC. However, patients
      who had received grafts from unrelated donors (URD) and had had full conditioning
      prior to HSCT were shown to have an increased risk of HC, compared to patients
      who had received HSCT from a related donor (RD) or patients who had received
      reduced intensity conditioning. In conclusion, HSCT patients with BK-viruria, an
      URD and receiving full conditioning have an increased risk of developing HC.

PMID- 16619540
TI  - Influence of age on the pattern and outcome of external beam radiotherapy for
      clinically localized prostate cancer.
AB  - BACKGROUND: The influence of age on the patterns and outcomes of external beam
      radiotherapy for clinically localized prostate cancer patients was examined.
      MATERIALS AND METHODS: The Japanese Patterns of Care Study surveys were used to
      compare the processes and outcomes of radical external beam radiotherapy in 140
      elderly patients (>75 years old) and 304 younger patients (<75 years old).
      RESULTS: Although the Karnofsky performance status was significantly different
      between elderly and younger patients, there were no significant differences in
      disease characteristics such as pretreatment PSA level, differentiation, Gleason
      combined score and clinical T stage. There were also no significant differences
      in the treatment characteristics such as CT-based treatment planning, conformal
      therapy, total radiation doses (both a median of 66.0 Gy) and hormonal therapy
      usage. Moreover, no significant differences in overall survival, biochemical
      relapse-free survival and late toxicity rates were observed between elderly and
      younger patients. CONCLUSION: Age did not influence the disease characteristics,
      patterns of external beam radiotherapy, survival and late toxicities for
      clinically localized prostate cancer patients. Therefore, radiotherapy could
      represent an important treatment modality for elderly patients as well as for
      younger ones.

PMID- 16619541
TI  - Alkylating agents and DNA polymerases.
AB  - Alkylating agents, for example nitrogen "mustards", are variably toxic,
      mutagenic, carcinogenic and teratogenic, but by mechanisms which have not been
      clearly established. In particular, the mechanisms both of their delayed toxic
      effects (which are primarily against dividing cells, in association with
      retardation of the rate of cell division, disruption of mitoses, and breakages
      and other abnormalities of chromosomes) and of their carcinogenic actions are not
      understood. The literature on the testing of thousands of analogues has
      demonstrated great variability of effects on the various cell biological
      phenomena, and no aspect of chemical structure or biochemical reactivity of these
      agents has been established as especially related to any particular effect. Here
      theories of the mechanisms of action of alkylating agents are reviewed and it is
      suggested that impairment of the functions of DNA polymerase complexes might
      contribute to some of the effects of alkylating agents. In particular, impairment
      of replicative fidelity of DNA during the S-phase could contribute to some of the
      mitotic and chromosomal effects, as well as to their carcinogenic and teratogenic
      potencies. Some aspects of testing the effects of alkylating agents on components
      of the DNA synthetic pathway are mentioned. Emphasis is given to consideration of
      the various relevant levels (conventional plasma/tissue; tissue/tumour cell
      cytoplasm; tumour cell cytoplasm/tumour cell nucleus and tumour nuclear
      karyoplasm/tumour chromatin] of the pharmacokinetics and pharmacodynamics of the
      agents and their metabolites.

PMID- 16619542
TI  - In vivo disposition of irinotecan (CPT-11) and its metabolites in combination
      with the monoclonal antibody cetuximab.
AB  - BACKGROUND: The present study was designed to investigate whether a combination
      of irinotecan and the monoclonal antibody cetuximab shows potential to modulate
      the pharmacokinetics of irinotecan and its metabolites. PATIENTS AND METHODS: All
      patients, suffering from advanced colorectal cancer, received irinotecan (350
      mg/m2) every third week and cetuximab as a loading dose (400 mg/m2) on day 2,
      followed by a weekly maintenance dose (250 mg/m2). Plasma samples were analysed
      after the first (MONO) and second (CMAB) irinotecan infusions. RESULTS: No
      significant alterations in the plasma concentrations and pharmacokinetics of
      irinotecan and its metabolites were observed after combination with cetuximab.
      Only differentiation of irinotecan into lactone and carboxylate plasma
      concentrations resulted in a distinctly lower cmax of the active lactone in the
      CMAB and a significantly higherAUClast in the MONO schedule (p<0.02). CONCLUSION:
      The results of this study indicated that cetuximab has no clinically relevant
      impact on the pharmacokinetics of irinotecan, its activation into SN-38, or its
      detoxification by beta-D-glucuronidation.

PMID- 16619543
TI  - Prognostic value of HSP27 in head and neck squamous cell carcinoma: a
      retrospective analysis of 57 tumours.
AB  - BACKGROUND: The aims of the present study were to assess the prevalence of HSP27
      expression in oral squamous cell carcinoma (OSCC) and to verify whether HSP27 can
      be considered to be a marker of prognosis in patients with OSCC. MATERIALS AND
      METHODS: The immunohistochemical expression of HSP27 was evaluated in 57 OSCC,
      who received standard treatment and monitoring. After grouping for HSP27
      expression, OSCCs were statistically analysed for the variables age, gender,
      histological grading, TNM, staging and survival rate. Univariate and multivariate
      analyses were performed. RESULTS: HSP27 was found to be reduced in 31 OSCC and
      was normally expressed in 26 OSCC. The pattern and intensity of HSP27
      immunolabelling did not show significant differences in relation to any variables
      retrospectively considered. In terms of prognostic significance, HSP27 reduced
      expression was found to have an independent association with the poorest overall
      survival rate (p=0.009; OR= 4.404; CI=1.444:13.427 by Cox regression).
      CONCLUSION: HSP27 reduced expression is an early marker of poor prognosis, useful
      in identifying aggressive biological behaviour in OSCC cases even before relapse.

PMID- 16619544
TI  - Prognosis of cerebellar glioblastomas: correlation between prognosis and
      immunoreactivity for epidermal growth factor receptor compared with
      supratentorial glioblastomas.
AB  - BACKGROUND: Cerebellar glioblastomas (GBM) are rare tumors whose
      clinicopathological characteristics are not well understood. PATIENTS AND
      METHODS: Clinico-immunohistochemical findings were retrospectively analyzed in 43
      supratentorial- and 7 cerebellar GBM. The correlation between survival and
      immunopositivity for p53, epidermal growth factor receptor (EGFR) and Ki-67 in
      these tumors was statistically analyzed and compared. RESULTS: Of the 43 patients
      with supratentorial GBM, 27 (62.8%) were EGFR immunopositive; their survival was
      significantly shorter than that of the 16 EGFR-negative patients (p=0.0248).
      There was no significant correlation between survival and p53 immunopositivity
      (p=0.7870) and Ki-67 labeling index (p =0.7133). All 5 cerebellar GBM patients
      treated with radio- and chemotherapy were EGFR-immunonegative; they survived
      significantly longer than patients with supratentorial GBM (p=0.0296) possibly
      because their EGFR negativity rendered their tumors more highly radiosensitive.
      CONCLUSION: The better prognosis of patients with cerebellar, EGFR-negative
      tumors compared to patients with supratentorial tumors is due to the higher
      radiosensitivity of these tumors.

PMID- 16619545
TI  - Expression of emmprin and matrix metalloproteinases (MMPs) in peripheral nerve
      sheath tumors: emmprin and membrane-type (MT)1-MMP expressions are associated
      with malignant potential.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs), including membrane-type (MT)-MMPs,
      correlate with biological aggressiveness in many carcinomas. However, their roles
      in peripheral nerve sheath tumors (PNSTs) have rarely been investigated.
      MATERIALS AND METHODS: In this study, the immunohistochemical expression of 6
      MMPs, their 3 inhibitors and emmprin, an MMP inducer, was examined in 14
      schwannomas, 14 neurofibromas and 12 malignant peripheral nerve sheath tumors
      (MPNSTs) in relation to malignant potentials. RESULTS: Higher expression levels
      (>3+) of emmprin and MT1-MMP were noted in 83.3% and 16.7% of MPNSTs,
      respectively, versus none in schwannomas and neurofibromas (p<0.0001). The
      overall expression rate (1-4+) of MT1-MMP was 58.3% in MPNSTs versus 7.1% in both
      schwannomas and neurofibromas (p=0.0093). Gelatinase A (MMP-2) showed higher
      expression levels (>3+) in all the tumors without significant differencies.
      Moreover, the expression patterns of MMP-1 and gelatinase B (MMP-9) could divide
      PNSTs into two groups: schwannoma versus neurofibroma/MPNST. Higher expression
      levels (>3+) of MMP-9 were observed in 50% of schwannomas versus none in
      neurofibromas and MPNSTs, while those of MMP-1 were found in 35.7% of
      neurofibromas and 66.7% of MPNSTs versus none in schwannomas. RECK was the main
      inhibitor expressed in these 3 tumors, with no significant differences.
      CONCLUSION: These results suggest that emmprin and MT1-MMP may be malignant
      potential-related proteins in PNSTs, and that MMP-1 and 9 may help
      differentiation between schwannoma and neurofibroma, especially in their
      plexiform types.

PMID- 16619546
TI  - Reduced galectin-3 expression is an indicator of unfavorable prognosis in gastric
      cancer.
AB  - BACKGROUND: Galectin-3 (gal-3) participates in a variety of biological events,
      including cell adhesion, proliferation, differentiation and apoptosis. The aim of
      this study was to determine the relationship of gal-3 expression with
      clinicopathological findings and prognosis in patients with gastric cancer.
      PATIENTS AND METHODS: Gal-3 and Ki-67 expressions were assessed by
      immunohistochemistry in 115 patients with gastric cancer. PCR-single strand
      conformation polymorphism (SSCP)-sequence analysis and the levels of gal-3 mRNA
      were also examined. RESULTS: The present study demonstrated that gal-3 expression
      was correlated with nodal status, lymphatic inivasion, pathological stage and
      histological parameters. On the other hand, gal-3 expression did not correlate
      with the expression of Ki-67. Reduced expression of gal-3 was significantly
      associated with a poor prognosis and multivariate analysis showed that gal-3
      expression was an independent prognostic factor. On PCR-SSCP-sequence analysis, 2
      single nucleotide polymorphisms (SNPs) were detected in the gal-3 gene, but none
      showed mutations. CONCLUSION: Reduced gal-3 expression was associated with lymph
      node metastasis, advanced stage and tumor differentiation in gastric cancer. Gal
      3 expression could be a useful prognostic factor in gastric cancer.

PMID- 16619547
TI  - Potential predictors of long-term survival after surgery for patients with stage
      IV colorectal cancer.
AB  - BACKGROUND: The prognosis of patients with colorectal cancer is considered to be
      affected by several factors. Recently, chemotherapy for this disease has been
      demonstrated to be effective for long-term survival. In this study, the potential
      predictors, including chemotherapy regimens for survival after surgery, in
      patients with stage IV colorectal cancer are presented. PATIENTS AND METHODS:
      Univariate and multivariate analyses of potential predictors of survival after
      surgery were carried out for 56 patients with stage IV colorectal cancer who had
      undergone surgery, including 22 with rectal and 34 with colon cancer. RESULTS:
      The survival in patients who had had a primary liver resection was longer than
      that in patients who had not (p=0.007). There was a significant difference among
      chemotherapy regimens (p=0.021). The survival in patients who were administered l
      leucovorin/5-fluorouracil (l-LV/5FU) was longer than that in patients who
      received uracil-tegafur (UFT) and cisplatin (CDDP)/5FU (p=0.024, p=0.004,
      respectively). In multivariate analyses, there were 5 favorable factors that
      influenced overall survival after surgery: lymph node metastasis (p=0.029), no
      bone metastasis (p=0.012), no peritoneal invasion (p=0.018), no primary liver
      resection (p=0.004) and the chemotherapy regimen (p=0.008). Furthermore, the
      survival in patients with a continued l-LV/5FU plus modified IFL regimen
      (additional irinotecan) was longer than for those patients who received other
      regimens, in both univariate and multivariate analyses. CONCLUSION: Five factors,
      namely lymph node metastasis, bone metastasis, peritoneal invasion, primary liver
      resection and chemotherapy, are potential predictors of survival after surgery
      for patients with stage IV colorectal cancer.

PMID- 16619548
TI  - Clinicopathological characteristics and outcome indicators of stage II gastric
      cancer according to the Japanese classification of gastric cancer.
AB  - BACKGROUND: The characteristics of stage II gastric cancer according to the
      Japanese Classification of Gastric Cancer (JCGC) were examined and the high-risk
      factors predicting poor prognosis were detected. PATIENTS AND METHODS: In total,
      107 patients, who underwent clinically curative gastrectomy with D2
      lymphadenectomy for stage II gastric cancer, were included. Survival curves of
      the depth of invasion, lymph node metastasis, the ratio of involved: resected
      lymph nodes and chemotherapy treatment were compared. RESULTS: The survival
      curves were related to tumor invasion depth and lymph node metastasis. The ratio
      of involved resected lymph nodes was a good prognostic indicator compared to the
      classification of regional lymph node metastasis (N classification). Survival
      rates with adjuvant chemotherapy were slightly higher than without adjuvant
      chemotherapy, but the difference was not significant. CONCLUSION: pT2pN1 (stage
      II) gastric cancers according to the JCGC, especially pSSpN1 cases, included
      stage IIIB and IV gastric cancers according to the International Union Against
      Cancer / American Joint Committee on Cancer (UICC/AJCC); therefore, the prognosis
      of these might be poor. With pSSpN1 cases, according to the JCGC, anticancer
      chemotherapy equivalent to that required for stage III gastric cancer cases is
      necessary.

PMID- 16619549
TI  - Thymidylate synthase and dihydropyrimidine dehydrogenase expressions in
      gallbladder cancer.
AB  - BACKGROUND: Although 5-Fluorouracil (5-FU) is widely used in chemotherapeutic
      treatment for gallbladder cancer, there is little evidence of its effectiveness.
      Thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are the major
      determinants of individual sensitivity to 5-FU, and the impact of TS and DPD
      expression on prognosis and 5-FU efficacy has been studied in gastrointestinal
      carcinomas. MATERIALS AND METHODS: TS and DPD enzymatic activities in frozen
      samples of 7 gallbladder cancer tissues and immunohistochemical TS and DPD
      protein expressions in 53 resected gallbladder cancers were evaluated. RESULTS:
      The DPD activity of gallbladder cancers was significantly higher than that of
      gastric and colon cancers (p=0.041). TS and DPD protein expressions increased in
      pT2 and pT3 cases compared to those in pT1 cases, and cases both with high TS and
      DPD expressions had a worse prognosis than both low TS and DPD expressions.
      However, TS and DPD expressions were not independent prognostic factors.
      CONCLUSION: TS and DPD protein expressions in gallbladder cancers were frequently
      high in pT2 and pT3 gallbladder cancers and control of high TS or DPD levels may
      be important for advanced gallbladder cancer therapy.

PMID- 16619551
TI  - Carcinogenesis in the remnant stomach following distal gastrectomy with billroth
      II reconstruction is associated with high-level microsatellite instability.
AB  - Although the gastric remnant has been reported to be at high risk for
      carcinogenesis, the process of carcinogenesis of gastric remnant cancer (GRC)
      remains unclear. In this study, genetic alterations in GRC were examined in order
      to investigate the carcinogenic pathways of GRC. Twenty-one patients with GRC
      were investigated and were compared to 36 patients with sporadic gastric cancer
      (GC) as a control group. Microsatellite instability (MSI) was examined using 8
      primer marker sets. Immunohistochemical staining for hMLH1 and hMSH2 as the DNA
      mismatch repair system was performed. The high-level MSI (MSI-H) frequency (43%;
      9/21) of GRC was significantly higher (p=0.001) than that of the sporadic GC (6%;
      2/36). The MSI-H incidence (67%: 8/12) of GRC after gastrojejunostomy (Billroth
      II anastomosis) was significantly (p=0.015) higher than that (11%: 1/9) after
      gastroduodenostomy (Billroth I anastomosis). The MSI-H in GRC was significantly
      (p<0.0001) associated with lack of expression of both hMLH1 and hMSH2. The
      inactivation of hMLH1 or hMSH2 was significantly frequent (p=0.035) in GRC after
      gastrojejunostomy (58%: 7/12), compared with that in gastroduodenostomy (11%:
      1/9). GRC was more closely associated with the MSI pathway than sporadic GC.
      Carcinogenesis in the remnant stomach following distal gastrectomy with
      gastrojejunostomy was found to be associated with the MSI pathway due to
      inactivation of the DNA mismatch repair system.

PMID- 16619550
TI  - Alternate paclitaxel-gemcitabine and paclitaxel-vinorelbine biweekly
      administration in non-small cell lung cancer patients: a phase II study.
AB  - BACKGROUND: In the present study, 3 cytotoxic agents were combined as front-line
      chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. All 3 drugs
      have been used in other 2-agent combinations and have been shown to be effective
      as first-line therapy. PATIENTS AND METHODS: Sixty-one (53 male, 8 female, median
      age 65 years old) out of 67 patients were evaluable for response and toxicity.
      Eighty percent of the patients were stage IIIB and IV and 20% were inoperable
      stage IIIA. In order to obviate toxicity as much as possible, paclitaxel 135
      mg/m2 was combined with gemcitabine 1000 mg/m2 for the first cycle, and 2 weeks
      later with vinorelbine 25 mg/m2, for the second cycle; this alternate schedule
      was repeated every 2 weeks for 9 cycles. RESULTS: No complete responses were
      observed; there was a 37.7% partial response rate and stable disease in 31.1% of
      the patients. The median survival was 13 months and 1-year survival, 53%.
      Myelotoxicity involved grade 3 neutropenia in 3.3% of the patients and grade 4 in
      1.6%. CONCLUSION: Adverse reactions were few in this alternate administration of
      paclitaxel-gemcitabine and paclitaxel-vinorelbine in NSCLC patients; in more than
      half of the patients there was long median and 1-year survival.

PMID- 16619552
TI  - Apoptosis in cervical cancer after balloon-occluded arterial infusion of
      anticancer drugs.
AB  - BACKGROUND: This study was designed to investigate the relationship between
      apoptosis and Bcl-2 and Bax expressions in uterine cervical cancer after balloon
      occluded arterial infusion (BOAI). MATERIALS AND METHODS: Twenty-four specimens
      were obtained before and after BOAI. The occurrence of apoptosis was examined
      with molecular biochemical techniques. The expressions of Bcl-2 and Bax proteins
      were investigated by immunohistochemical staining. RESULTS: Labelling of DNA in
      situ indicated that apoptotic cells were sporadically seen before BOAI (6.1 +/-
      1.9). Apoptotic cells apparently increased at 5 days (25.1 +/- 6.4) after BOAI
      The autoradiographic analysis revealed that the DNA-ladder was identified at 5
      days after BOAI. Although Bcl-2 immuno-reactivity was faintly detected, the
      expression of Bax increased at 3 days (49.4 +/- 10.4%) after BOAI. CONCLUSION:
      The results indicated that treatment with BOAI resulted in transient increases of
      apoptosis in cervical cancer in association with the increased expression of Bax.

PMID- 16619553
TI  - Tumor-associated tissue eosinophilia in human esophageal squamous cell carcinoma.
AB  - BACKGROUND: Inflammatory cell infiltration around the sites of carcinoma invasion
      is believed to play important roles in carcinoma biological behavior. MATERIALS
      AND METHODS: The status of inflammatory cell infiltration at the sites of frank
      invasion in 97 cases of esophageal squamous cell carcinoma (SCC) were examined,
      with special emphasis on the status of tumor-associated tissue eosinophilia
      (TATE). Infiltration of the CD4+T-cells, CD8+T-cells, CD68+macrophages, L26+B
      cells, mast cells and eosinophils was quantitatively evaluated in histological
      tissue sections. The results were then statistically correlated with
      clinicopathological factors. RESULTS: Among tumor-associated inflammatory cells,
      the number of tumor-associated eosinophils was significantly correlated with the
      presence or absence of vascular invasion, lymph node (LN) metastasis and
      recurrence. The cases were tentatively classified into 2 categories, small and
      large groups, according to the median and/or average number of tissue
      eosinophils. The survival curve of the patients was evaluated according to this
      classification. No statistically significant differences were detected between
      these 2 groups in the cases without LN metastasis. However, the large group was
      associated with a statistically significant better prognosis in cases associated
      with LN metastasis, especially in those with invasion to adventitia (T3) of the
      esophagus. CONCLUSION: The possible function of tumor-associated eosinophils has
      not yet been elucidated, but these findings indicate the importance of TATE in
      the biological behavior of SCC of the esophagus.

PMID- 16619554
TI  - Clinical impact of adjuvant chemotherapy on patients with stage III colorectal
      cancer: l-LV/5FU chemotherapy as a modified RPMI regimen is an independent
      prognostic factor for survival.
AB  - BACKGROUND: Patients with stage III colorectal cancer have a substantial risk of
      microscopic metastatic disease at the time of resection. Treatment with
      leucovorin (LV)/5-Fluorouracil (5FU) has been demonstrated to be effective for
      advanced colorectal cancer; however, the clinical impact of l-LV/5FU is still
      unclear. 1-LV/5FU for patients with stage III colorectal cancer may play an
      important role, as an adjuvant chemotherapy, in improving survival. PATIENTS AND
      METHODS: The clinicopathological features of 36 patients receiving adjuvant l
      LV/54 administration and 16 not, univariate analysis of potential predictors of
      overall survival and disease-free survival, relative risk of overall survival and
      disease-free survival by multivariate analysis and the occurrence of chemotherapy
      induced toxic effects were studied in 52 patients with stage III colorectal
      cancer, including 30 with rectal and 22 with colon cancer, who had undergone
      surgery. RESULTS: No significant differences were found in the
      clinicopathological features of the 2 groups. On univariate analysis, there were
      no significant differences in overall survival in either group; disease-free
      survival in patients with adjuvant I-LV/5FU was longer than that in patients
      without it (p<0.001). Moreover, multivariate analysis demonstrated that I-LV/5FU
      adjuvant chemotherapy was an independent prognostic factor in terms of disease
      free survival (p =0.001; RR, 17.492; 95% CI, 3.298-92.778). CONCLUSION: I-LV/5FU
      adjuvant chemotherapy in patients with stage III colorectal cancer is important
      as an independent prognostic factor in terms of disease-free survival.

PMID- 16619555
TI  - Role of the MTT chemosensitivity test in the prognosis of gastric cancer patients
      after postoperative adjuvant chemotherapy.
AB  - The clinical usefulness of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide (MTT) chemosensitivity test (MTT assay; MTTA) in the
      selection of anticancer drugs against advanced gastric cancer (AGC) was
      evaluated. MTTA is widely used to predict patient responses to particular drugs,
      allowing for the selection of appropriate chemotherapeutic drugs and the
      avoidance of ineffective chemotherapeutic drugs, thereby improving patient
      survival. Since 1989, we have accumulated MTTA efficacy data from AGC patients.
      In this study, the present clinical roles of MTTA and the data from 202 patients
      with stage III or IV gastric cancer analyzed for survival outcome following
      surgery, with or without postoperative chemotherapy, evaluated by MTTA, are
      discussed. The patients were divided into 3 groups; an adapted group found to be
      sensitive to chemotherapy by MTTA, a non-adapted group found to be insensitive to
      chemotherapy by MTTA and a group that received no chemotherapy. For stage III
      gastric cancer patients, the adapted group had a statistically better survival
      rate compared to the other groups, while for stage IV patients, there was no
      difference in survival rate between any of the groups. However, further
      classification of stage IV patients as to the presence or absence of peritoneal
      dissemination (P) showed that the adapted group with P showed better prognoses
      than the other groups with P. The analysis of data collected since 2000 revealed
      that the 11 patients in the taxane-adapted group, who received chemotherapeutic
      regimens that included taxanes and were found to be sensitive to taxanes by MTTA,
      demonstrated better survival than the taxane non-adapted group (n=11) (p=0.045).
      In conclusion, MTTA results predicted patient prognoses, based on the selection
      of appropriate chemotherapy.

PMID- 16619556
TI  - Predicting treatment outcome in cervical diseases using liquid-based cytology,
      dynamic HPV genotyping and DNA cytometry.
AB  - BACKGROUND: In this study, our prospective experience with a multimodal follow-up
      protocol is summarized, with special emphasis on predicting the treatment outcome
      of cervical diseases. MATERIALS AND METHODS: Liquid-based cytology samples
      (ThinPrep) from 209 women exhibiting the whole spectrum of human papilloma virus
      (HPV)-related cervical diseases were investigated by cytology, PCR-based HPV
      genotyping and DNA cytometry pre-surgery. The first control cytology and type
      specific HPV tests were performed at 3 months post-surgery. RESULTS: The success
      rate of surgery was 95% in eradicating high-grade cervical disease and 90% in
      eliminating the baseline HPV genotype. Treatment failure was significantly
      correlated with baseline cytology (p=0.011), resection margin status (p=0.016)
      and HPV positivity at 3 months post-surgery (p=0.04). Multivariate logistic
      regression analysis showed that type-specific persistent HPV infection (p=0.028),
      baseline cytology (p=0.039) and histology (p=0.065) were independent predictors
      of residual cervical neoplasias. CONCLUSION: Our results showed that our
      multimodal surveillance protocol may help to individually assess the anticipated
      clinical outcome of cervical diseases post-surgery.

PMID- 16619557
TI  - Clinical features and surgical outcome of hepatic caudate lobe metastases from
      colorectal cancer.
AB  - BACKGROUND: The difficulty encountered in hepatectomy for the removal of a
      malignant tumor in the hepatic caudate lobe has recently been reported. However,
      few reports have described the clinical features of hepatic caudate lobe
      metastases from colorectal carcinoma. PATIENTS AND METHODS: Retrospective
      clinicopathological data for 13 consecutive patients with colorectal metastases
      to the hepatic caudate lobe were analyzed for their various clinical aspects and
      long-term outcomes. RESULTS: The tumor-free margin of the resected specimen was
      significantly smaller in the hepatic caudate lobe metastases group than in the
      other 178 patients with colorectal metastases in other sites of the liver
      (p<0.01), while the invasiveness of hepatectomy, as judged by the volume of liver
      resected and the duration of the procedure, was higher in the hepatic caudate
      lobe metastases group. Hepatic disease-free survival rates in the caudate lobe
      metastases group were lower than in the other group (p<0.01). By multivariate
      analysis, metastases to the hepatic caudate lobe negatively impacted hepatic
      disease-free survival (adjusted relative risk, 2.085; p=0.048). CONCLUSION: In
      patients with hepatic caudate lobe metastases, hepatectomy with clear surgical
      margins is difficult, even when major hepatectomy is attempted. Hepatic
      metastasis in the caudate lobe is a risk factor for early liver recurrence after
      hepatectomy.

PMID- 16619558
TI  - A phase I study of bi-weekly combination therapy with S-1 and docetaxel for
      advanced or recurrent gastric cancer.
AB  - BACKGROUND: S-1 is a novel oral fluorouracil antitumor drug that contains a
      combination of 3 pharmacological agents: tegafur (FT), a 5-fluorouracil (5-FU)
      prodrug, 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits the activity of
      dihydropyrimidine dehydrogenase (DPD), and potassium oxonate (Oxo), which reduces
      the gastrointestinal toxicity of 5-FU. S-1 and docetaxel have both been
      identified as effective agents for the treatment of gastric cancer. However,
      little is known about the effects and/or adverse effects of a combination of
      these drugs in the treatment of gastric cancer. The aim of this phase I study was
      to determine the maximum-tolerated dose (MTD) and the recommended dose of
      docetaxel with a fixed dose of S-1 in patients with advanced or recurrent gastric
      cancer. PATIENTS AND METHODS: Patients with metastatic, recurrent, or
      unresectable gastric cancer received docetaxel at a starting dose of 25 mg/m2 by
      i.v. infusion over 1 h on days 1, 15 and 29, and S-1 at the full dose of 80 mg/m2
      daily for 4 weeks of every 6 weeks. Nine patients were treated with increasing
      dosages of docetaxel as follows: (docetaxel/S-1, mg/m2): 25/80 (level 1), 30/80
      (level 2) and 35/80 (level 3). All cases were assessable for drug safety and 7
      were assessable for response. Colony-stimulating factor (CSF) was not used in
      this study. The adverse effects of treatment were analyzed according to NCI-CTC,
      version 2 and the response was assessed according to the Japanese Classification
      of Gastric Cancer, 13th Ed. RESULTS: The MTD was reached at the 35/80 mg/m2 dose
      level in 3 out of 3 patients. These patients experienced some dose-limiting
      toxicity (DLT) or grade 3 anemia. The reported DLTs included diarrhea, stomatitis
      and general fatigue. Due to these results, 3 additional patients were not
      enrolled at this dose-level. No hematological or non-hematological adverse
      effects (more severe than grade 2) were observed in any of the level 1 or 2
      patients. However, among the level 1 patients, 66.7% developed grade 2
      leukocytopenia and 33.3% developed grade 2 neutropenia. Among the level 2
      patients, 33.3% developed grade 2 appetite loss, diarrhea and general fatigue.
      Partial responses were achieved in 3 (42.9%) out of the 7 patients with evaluable
      lesions. These results indicated that the appropriate doses of the 2 drugs in
      combination therapy are 30 mg/m2 for docetaxel and 80 mg/m2 for S-1. CONCLUSION:
      The S-1/docetaxel drug combination showed a good safety profile, with diarrhea
      and general fatigue being common, but manageable, adverse reactions. Moreover,
      the responses observed in this study suggest that the drug combination shows a
      high degree of efficacy in patients with advanced and/or recurrent gastric
      cancer.

PMID- 16619559
TI  - Management satisfaction in survivors of testicular cancer.
AB  - BACKGROUND: The aim of this study was to examine satisfaction with the quality of
      the doctor-patient relationship (QCD) and the information (INF) made available,
      as well as the influence of different treatment modalities and psychosocial
      variables in testicular cancer survivors (TCSs). MATERIALS AND METHODS: Two
      hundred and 6 TCSs, seen at 2 Norwegian university hospitals, were studied
      retrospectively and currently in a cross-sectional follow-up design.
      Questionnaires were filled in prior to and at the patients' follow-up
      examination. The mean length of time since their management period had ended was
      6.5 years (range 0-17 years). RESULTS: The QCD was rated higher than the INF. The
      QCD was also the strongest contributor to the variance in the INF. The patients
      in the surveillance group had the lowest QCD. CONCLUSION: The relatively high QCD
      scores may reflect the fact that the patients had been cured from a life
      threatening disease. The low INF scores may indicate that the TCSs were poorly
      informed about the potential health problems related to their treatment. Thus, it
      is suggested that more attention should be focused on the education of the
      patients.

PMID- 16619560
TI  - Clinical usefulness of fused PET/CT compared with PET alone or CT alone in
      nasopharyngeal carcinoma patients.
AB  - The diagnostic accuracy of fused positron emission tomography/computed tomography
      (PET/CT) was compared with CT alone and PET alone in the staging and re-staging
      of nasopharyngeal carcinoma (NPC) patients. PATIENTS AND METHODS: Eighty-six
      fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT studies were retrospectively
      performed in 70 patients with NPC, 20 patients for primary tumor staging and 50
      patients for re-staging after treatment. Each lesion was analyzed visually and
      assigned a score on a 5-point scale. Each study was interpreted in 3 ways: PET
      images were evaluated in the absence of CT data, CT images in the absence of PET
      data and fused PET/CT images. The results of these images were correlated with
      histological findings, as well as long-term radiological and clinical follow-up
      (the shortest follow-up period after imaging was 6 months). PET, CT and PET/CT
      accuracy were compared by a McNemar test. RESULTS: Fused PET/CT correctly
      characterized the tumor-node-metastasis system stage in 82 out of 86 studies
      (95.4%; 95% CI: 90.9% to 99.9%). PET alone and CT alone were found to be accurate
      in 71 out of 86 studies (82.6%; 95% CI: 74.5% to 90.6%) and 63 out of 86 studies
      (73.3%; 95% CI: 63.9% to 82.6%), respectively. Furthermore, the differences
      between PET/CT and either PET alone or CT alone were statistically significant
      (p<0.05). Overall, the study-based analysis of PET/CT for staging NPC
      demonstrated 48 true-positive, 2 false-negative, 34 true-negative and 2 false
      positive studies. The sensitivity, specificity, accuracy, positive predictive
      value and negative predictive value of FDG-PET/CT studies for staging NPC were
      96%, 94.4%, 95.4%, 96% and 94.4%, respectively. CONCLUSION: PET/CT is more
      accurate than PET alone or CT alone for the depiction of NPC. Fused PET/CT is a
      valuable imaging tool in patients for staging diagnosis of NPC.

PMID- 16619561
TI  - Prognostic and predictive impact of soluble epidermal growth factor receptor
      (sEGFR) protein in the serum of patients treated with chemotherapy for metastatic
      breast cancer.
AB  - BACKGROUND: A soluble fragment of the epidermal growth factor receptor (EGFR)
      extracellular domain (sEGFR) can be detected in the serum of cancer patients, but
      the role of sEGFR is still unclear. MATERIALS AND METHODS: Blood samples from
      patients receiving chemotherapy for metastatic breast cancer were collected
      before (n = 101) and after 3 courses of therapy (n=39). Levels of sEGFR and serum
      HER-2/neu extracellular domain (ECD) were determined by standardized ELISA.
      RESULTS: A higher percentage of cancer patients (15%) showed sEGFR values below
      45ng/mL compared with control subjects (3%, p<0.001). Patients with sEGFR levels
      below 45 ng/mL showed a trend towards shorter overall survival (median 11.7
      versus 15.4 months, p=0.08), which was more pronounced in patients with estrogen
      receptor-positive primary tumors (median 9.6 versus 15.4 months, p=0.022)
      Patients with low sEGFR and elevated serum HER-2/neu ECD (>15 ng/mL) also showed
      a shorter overall survival than those with normal values for both parameters (7.1
      versus 15.4 months, p=0.03). Again, this difference was higher in patients with
      estrogen receptor-positive tumors (4.6 versus 15.4 month, p<0.0001). During
      treatment, a decrease of sEGFR levels occurred in 74.4% of the patients
      (p=0.014). CONCLUSION: Low sEGFR levels in patients with metastatic breast cancer
      are associated with a shorter overall survival, particularly in patients with
      estrogen receptor-positive tumors. Chemotherapy frequently induces a decrease of
      sEGFR. The combined, determination of sEGFR and serum HER-2/neu ECD also delivers
      relevant information. These findings suggest that the sEGFR status in metastatic
      breast cancer could be of clinical relevance.

PMID- 16619562
TI  - Liposomal oxaliplatin in the treatment of advanced cancer: a phase I study.
AB  - BACKGROUND: Lipoxal is a liposomal oxaliplatin, which reduces the cytotoxic
      agent's adverse reactions without reducing effectiveness. Our objectives were to
      determine the adverse reactions, dose-limiting toxicity (DLT) and the maximum
      tolerated dose (MTD) of lipoxal. PATIENTS AND METHODS: Twenty-seven patients with
      advanced disease of the gastrointestinal system were included in the study. All
      patients had been pretreated with standard chemotherapy according to established
      guidelines. At entry, all patients had recurrent or progressive disease (stage IV
      gastrointestinal cancers: colorectal, gastric and pancreatic). Six lipoxal dose
      levels (100 mg/m2, 150 mg/m2, 200 mg/m2, 250 mg/m2, 300 mg/m2 and 350 mg/m2) were
      set and at least 3 patients were included at each level. Eight patients were
      treated at 300 mg/m2 (MTD). The treatment was given once weekly for 8 weeks.
      RESULTS: No serious side-effects were observed at the first 4 dose levels (100
      250 mg/m2). At levels 5 and 6, mild myelotoxicity and nausea were observed. The
      most common adverse reaction was grade 2-3 peripheral neuropathy, observed in all
      4 patients treated at 350 mg/m2. The 350 mg/m2 dose level was therefore
      considered as DLT and the 300 mg/m2 level as the MTD. Of the 27 patients, 3
      achieved partial response and 18 had stable disease for 4 months, (range 2-9
      months). CONCLUSION: The most common toxicity was peripheral neuropathy at the
      300 and 350 mg/m2 dose levels. Lipoxal was well-tolerated and greatly reduced all
      the other side-effects of oxaliplatin, especially myelotoxicity and
      gastrointestinal tract toxicities. These preliminary results showed adequate
      effectiveness in pretreated patients.

PMID- 16619563
TI  - Randomized phase II trial of OK-432 in patients with malignant pleural effusion
      due to non-small cell lung cancer.
AB  - To determine the optimum dose of OK-432 for intrathoracic administration, a
      multicenter randomized phase II trial was conducted in patients with malignant
      pleural effusion due to non-small cell lung cancer. Patients with histologically-
      or cytologically-proven malignant pleural effusions were randomized to arm A (10
      Klinische Einheit (KE) of OK-432) or arm B (1 KE of OK-432). OK-432 was injected
      intrapleurally over 30 min on days 1 and 3 and the chest tube was clamped for 6
      h. If control was inadequate on day 8, 10 KE was administered on days 8 and 10 in
      each treatment arm. Forty patients were enrolled and 38 patients were eligible
      (19 in arm A and 19 in arm B). The effusion control rate on day 8 was 79% in arm
      A and 53% in arm B, while control rates on day 28 were 74% and 84%, respectively.
      The median drainage time after administration was significantly shorter in arm A
      (4.0 +/- 1.2 days) than in arm B (7.0 +/- 1.7 days). The total drainage volume
      was also significantly less in arm A than in arm B. No grade 4 toxicities or
      treatment-related deaths were observed in either treatment arm. Intrathoracic
      injection of OK-432 is a feasible treatment for malignant pleural effusion.
      Although the malignant pleural effusion control rate was equivalent in each
      treatment arm, faster control and less drainage were achieved in arm A. A dose of
      OK-432 10 KE/body is, therefore, recommended for further trial.

PMID- 16619564
TI  - Planned sequence of gemcitabine followed by vinorelbine in the treatment of
      elderly patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: The rationale for planned sequential chemotherapy is based on the
      principle that sequential administration of non-cross-resistant cytotoxic agents
      has the advantage of eliminating additive toxicity and permitting the delivery of
      full doses of each drug. At present, there is a lack of data on the results of
      planned sequential single agent administration in elderly patients with advanced
      non-small cell lung cancer (NSCLC). The aim of this study was to explore the
      possibility of increasing the time-to-progression (TTP) by a 1.5 factor in
      comparison with the historical results of monochemotherapy with a first-line
      planned sequential administration of gemcitabine (GEM) and vinorelbine (VNR).
      PATIENTS AND METHODS: GEM 1000 mg/m2 was administered intravenously (i.v.) for 30
      min on days 1, 8 and 15 and recycled on day 28 for a total of 3 cycles.
      Independently of response, VNR was administered i.v. as a bolus at a dose of 25
      mg/m2 on days 1, 8 and 15 of a 28-day cycle. VNR treatment was continued until
      disease progression or intolerance. RESULTS: Fifty-two consecutive patients, with
      a median age of 76 years (70-85), affected by locally advanced (35%), metastatic
      (54%) or recurrent (11%) NSCLC were enrolled. The overall best objective response
      was 3.8% CR, 19.2% PR, 32.7% SD, 23.1% disease progression and 21.2% not
      evaluable. Both drugs were well tolerated. The median TTP was 6 months (95%
      confidence limits 4-8), the median overall survival was 10 months (95% confidence
      limits 6-14) and the one-year survival rate was 42%. CONCLUSION: The planned
      sequential administration of GEM and VNR suggests that the TTP can be increased
      with the use of the 2 single agents in elderly patients with locally advanced or
      metastatic NSCLC.

PMID- 16619565
TI  - Results of radiation therapy for superficial esophageal cancer using the standard
      radiotherapy method recommended by the Japanese Society of Therapeutic Radiology
      and Oncology (JASTRO) Study Group.
AB  - BACKGROUND: Superficial esophageal cancer (SEC) is defined as esophageal cancer
      limited to the submucosal layers, including mucosal cancer and submucosal cancer,
      and is squamous cell carcinoma in most patients. In 2000, the Japanese Society of
      Therapeutic Radiology and Oncology (JASTRO) Study Group for SEC published a
      consensus guideline of standard radiotherapy methods. In this study, the interim
      treatment outcomes of SEC patients, who had received radiation therapy following
      the standard radiotherapy methods, were investigated. PATIENTS AND METHODS: From
      2000 to 2003, a total of 141 SEC patients were treated in 24 institutions in
      Japan. RESULTS: The 1-, 2- and 3-year survival rates were 95%, 90% and 90%,
      respectively, for patients with mucosal cancer and 90%, 81% and 70%,
      respectively, for patients with submucosal cancer. The overall survival was
      better in patients who had undergone chemotherapy than in patients who had
      received radiation therapy alone, though the difference was not statistically
      significant. The clinical target volume (CTV) did not influence overall survival
      and intracavitary irradiation did not influence the local control rate in either
      patients with mucosal or submucosal cancer. Radiation-induced esophageal ulcer
      was not observed in this series. CONCLUSION: The standard radiotherapy methods
      are safe and effective for treating SEC. However, the usefulness of chemotherapy
      and intracavitary irradiation and the optimal setting of the CTV should be
      clarified by future randomized trials.

PMID- 16619566
TI  - Expression of MAGE A 1-6 mRNA in sputa of head and neck cancer patients--a
      preliminary report.
AB  - BACKGROUND: The applicability of the melanoma antigen gene (MAGE) to the
      molecular diagnosis of cancer, by detecting MAGE mRNA in the sputa of head and
      neck cancer patients, was investigated. MATERIALS AND METHODS: Nested reverse
      transcription-polymerase chain reaction (RT-PCR) with the MAGE common primers
      designed to detect MAGE A1-6 genes was conducted with sputa of 17 head and neck
      squamous cell carcinoma patients. RESULTS: Of the 17 sputa specimens from
      patients with squamous cell carcinoma, MAGE mRNA was detected in 13 cases, while
      the detection rate was 2 out of 40 in the normal control group, showing
      significant correlation (p<0.05) between head and neck squamous cell carcinoma
      and MAGE mRNA expression in sputa. CONCLUSION: MAGE may be a useful tumor marker
      of head and neck cancer.

PMID- 16619567
TI  - Quality of life is improved in breast cancer patients by Standardised Mistletoe
      Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo
      controlled, double-blind, multicentre clinical trial.
AB  - The objective of this randomised, multicentre, double-blind clinical trial was to
      investigate the impact of PS76A2, an aqueous mistletoe extract standardised to
      mistletoe lectins, on quality of life (QoL) in breast cancer patients. A total of
      352 patients were randomly allocated to 2 groups receiving PS76A2 (15 ng
      mistletoe lectin/0.5 ml) or matching placebo twice weekly for 4 to 6 cycles of
      CMF (cyclophosphamide, methotrexate, fluorouracil) chemotherapy followed by 2
      months follow-up. The primary efficacy end-point was the change from baseline of
      3 FACT-G subscales (physical, emotional and functional well-being) during the
      fourth CMF cycle. Secondary measures included GLQ-8 (8 linear analogue self
      assessment scales), Spitzer's uniscale and haematological variables. The main
      variables of safety analysis were adverse events, including injection site
      reactions and clinical laboratory tests. The results showed that physical,
      emotional and functional well-being improved upon PS76A2, but deteriorated
      following placebo. The treatment differences were statistically significant for
      the 3 subscales as well as for the summary score FACT-G, which was analysed as
      O'Brien's rank sum of its 3 subscales: The total score increased by 4.40 +/-
      11.28, indicating a higher QoL after PS76A2, but decreased by 5.11 +/- 11.77 with
      placebo (p<0.0001). The GLQ-8 sum of 8 LASA scales was analysed as a summary
      score of GLQ-5 (sum of item nos. 1, 5, 6, 7, 8) and GLQ-3 (sum of item nos. 2, 3,
      4). GLQ-5 characterises typical aspects of QoL, while GLQ-3 consists of 3 side
      effects of CMF (feeling sick, numbness or pins and needles, loss of hair). GLQ-5
      decreased by 42.9 +/- 125.0 upon PS76A2, indicating an improvement in QoL, but
      increased by 60.3 +/- 94.0 upon placebo (p<0.0001). GLQ-3 deteriorated in both
      groups (PS76A2: 13.9 +/- 52.4; placebo: 34.5 +/- 57.0), but the differences in
      favour of PS76A2 were, nevertheless, statistically significant (p=0.0007). The
      total score GLQ-8 improved by 28.9 +/- 154.6 after PS76A2 and deteriorated by
      94.8 +/- 141.1 after placebo (p<0.0001). Spitzer's uniscale improved by 12.2 +/-
      30.7 upon PS76A2 and deteriorated by 10.8 +/- 26.1 with placebo (p<0.0001). After
      follow-up without chemotherapy, a significant treatment difference in favour of
      PS76A2 was determined by means of FACT-G, GLQ-8 and Spitzer's uniscale. PS76A2
      was well tolerated in this trial, with the exception of slight local reactions in
      17.6% of the PS76A2 group. In conclusion, PS76A2 (15 ng mistletoe lectin/0.5 ml
      twice weekly) was shown to be safe and effective in improving QoL in breast
      cancer patients during chemotherapy and follow-up.

PMID- 16619568
TI  - Increased urinary levels of tissue polypeptide specific antigen (TPS) in
      alcoholics.
AB  - BACKGROUND: Urinary levels of tissue polypeptide specific antigen (TPS,
      cytokeratin-18) have been proposed as a marker of urothelial malignancies.
      Previous studies have shown that serum TPS levels are elevated in alcoholics.
      This study was designed to determine whether alcoholics had elevated urinary TPS
      levels as well. PATIENTS AND METHODS: Serum and urinary TPS levels were
      determined in 24 alcoholics and 15 healthy controls by means of a commercial
      chemiluminiscent immunoassay. RESULTS: Serum TPS levels were higher in alcoholics
      than in controls (median 332 U/L, range 51-21241 U/L versus median 17 U/L, range
      15-65 U/L, respectively, p<0.001). Urinary TPS levels were also higher in
      alcoholics than in controls (median 244 U/L, range 22-1267 U/L versus median 66.5
      U/L, range 15-600 U/L, respectively, p=0.001). Urinary TPS levels were correlated
      with serum TPS levels in alcoholics. CONCLUSION: Urinary TPS levels are elevated
      in alcoholics. Consequently, the specificity of urinary TPS as a tumor marker may
      be limited in alcoholics.

PMID- 16619569
TI  - MLH1 mismatch repair gene product is associated with apoptotic potential of
      urothelial bladder carcinomas.
AB  - BACKGROUND: Mismatch repair genes are possibly involved in the tumorigenesis
      and/or progression of bladder cancer, as has been reported in colorectal and
      other cancers. MATERIALS AND METHODS: The protein expression of one of these
      genes (MLH1) was examined in 121 patients with urothelial carcinoma (UC) of the
      bladder by an immunohistochemical technique. RESULTS: Reduced expression of MLH1
      protein was detected in 56 cases (46%) and was significantly more frequent in pT2
      UCs (p=0.039). In superficial disease (Ta-T1 tumors), preserved expression of the
      MLH1 protein was detected in tumors with high proliferation indices, as evidenced
      by Ki-67 immunostaining (p=0.046). Interestingly, low MLH1 levels were positively
      associated with the possibly low apoptotic potential of the tumor cells, as
      evidenced by decreased caspase-3 (CPP32) immunoreactivity (p=0.050). CONCLUSION:
      A significant proportion of UCs revealed low positivity percentages for MLH1
      expression, probably reflecting MLH1 gene dysfunction in the respective cases.
      Preserved MLH1 expression was associated with highly proliferating cells, which
      are more likely to need DNA repair systems. A reduced expression of MLH1 may
      exert an adverse influence on the apoptotic potential of cancer cells.

PMID- 16619570
TI  - Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2) are
      prognostic factors in cervical cancer, related to invasive disease but not to
      high-risk human papillomavirus (HPV) or virus persistence after treatment of CIN.
AB  - OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (TIMP-2)
      are important regulators of cancer invasion and metastasis. Their associations to
      high-risk (HR) human papillomavirus (HPV) in cervical intra-epithelial neoplasia
      (CIN) and cervical cancer (CC) are unexplored and their prognostic significance
      in CC remains controversial. MATERIALS 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 MMP-2 and TIMP-2 and tested for HPV using
      PCR with 3 primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available
      from all squamous cell carcinoma patients and 67 CIN lesions had been monitored
      with serial PCR for HPV after cone treatment. RESULTS: MMP-2 increased with the
      grade of CIN, with major up-regulation upon transition to invasive cancer (OR
      20.78) (95%CI 7.16-60.23) (p=0.0001). TIMP-2 retained its normal expression until
      CIN3, with dramatic down-regulation in invasive disease (p=0.0001 for trend).
      Thus, the MMP2:TIMP-2 ratio increased with progressive CIN, exceeding the value
      1.0 only in invasive disease. Both MMP-2 and TIMP-2 are highly specific (TIMP-2;
      100%) discriminators of CIN with 100% positive predictive value (TIMP-2), but
      suffer from low sensitivity and negative predictive value. Neither MMP-2 nor TIMP
      2 showed any significant association with HR HPV or virus persistence/clearance.
      TIMP-2 (but not MMP-2) was a significant predictor of survival in univariate
      (Kaplan-Meier) analysis (p=0.007), but lost its significance in multivariate
      (Cox) analysis. CONCLUSION: The activities of MMP-2 and TIMP-2 in cervical
      carcinogenesis seem to be unrelated to HR-HPV The inverse MMP-2:TIMP-2 ratio is a
      sign of poor prognosis. A combination of a TIMP-2 assay with another test showing
      high SE and high NPV (e.g., HCII for HPV) should provide a potential screening
      tool capable of accurate detection of CIN.

PMID- 16619571
TI  - A randomized study to assess the effectiveness of orally administered pilocarpine
      during and after radiotherapy of head and neck cancer.
AB  - BACKGROUND: This prospective randomized study was undertaken to assess the
      effectiveness of oral pilocarpine chloratum (Salagen) during and after
      radiotherapy. PATIENTS AND METHODS: Between October 1999 and December 2003, 66
      patients received 60 Gy of irradiation to their head and neck cancer. Half of the
      patients received 5 mg oral pilocarpine 3 times a day from the beginning of
      radiotherapy over a period of 12 weeks. The control group received similar doses
      of pilocarpine only in the second 6 weeks following irradiation. Patient saliva
      secretion was recorded, and a visual analog scale measuring overall and daily
      xerostomia, difficulty in sleeping, speaking, eating and wearing dentures was
      employed. RESULTS: Pilocarpine, given concomitantly with radiotherapy,
      statistically improved the salivary flow and induced better patient comfort by
      the end of radiotherapy. Patient comfort and symptoms related to xerostomia
      greatly decreased compared to patients receiving pilocarpine after irradiation in
      the second 6-week period of therapy. The patients' quality of life, saliva
      production and symptoms related to xerostomia showed significant progress by the
      end of the 12 weeks. CONCLUSION: The results suggest that stimulated salivary
      glands suffer less decrease in saliva production during radiotherapy. The
      stimulated saliva flow reduced the side-effects of irradiation.

PMID- 16619572
TI  - Development of mantle cell lymphoma in a patient with adrenocortical carcinoma
      and an 18-year survival after complete removal of the primary cancer and
      resection of local recurrences.
AB  - The case of a patient with a non-functional and poorly-differentiated
      adrenocortical carcinoma, who had an unexpected long-term survival after a right
      adrenalectomy and subsequent removal of 2 local recurrences, is reported.
      However, fifteen years after the complete resection of the primary neoplasm, the
      patient first developed an autoimmune thrombocytopenic purpura and later a mantle
      cell lymphoma located in the mediastinal lymph nodes. This case confirms the
      possible growth of a second tumour in patients with adrenocortical carcinomas,
      especially if presenting a long survival after resection of the primary
      malignancy, and emphasises the need for the close follow-up of these patients.

PMID- 16619573
TI  - Multigene real-time PCR detection of circulating tumor cells in peripheral blood
      of lung cancer patients.
AB  - BACKGROUND: CLCA2, HMGB3, L587S and ASH1 were identified in lung cancer tissues
      using genetic subtraction, microarray and quantitative PCR, and found to be
      specific and complementary for detection of non-small cell lung carcinoma (NSCLC)
      and small cell lung carcinoma (SCLC). MATERIALS AND METHODS: A real-time RT-PCR
      assay, simultaneously detecting four genes, was developed and tested on lung
      cancer specimens. RESULTS: Twenty-two out of 24 adenocarcinomas, 18/18 squamous,
      4/5 large cell, 2/2 small cell and 2/2 bronchoalveolar/neuroendocrine cancer
      tissue samples tested positive. Specificity was demonstrated by evaluation of 194
      other tumor and corresponding normal tissues. Circulating tumor cells in the
      peripheral blood of 49/108 lung cancer patient samples tested positive, and
      general correlations of multigene expression signals to disease status were
      observed. Changes in multigene expression during treatment and disease recurrence
      in individual patients could be detected. CONCLUSION: These data indicate the
      diagnostic and prognostic utility of a multigene real-time RT-PCR assay to detect
      tumor cells in the peripheral blood of lung cancer patients.

PMID- 16619574
TI  - Retroperitoneal soft tissue sarcomas: prognosis and treatment of primary and
      recurrent disease in 117 patients.
AB  - BACKGROUND: The objective of this study was to define prognostic factors for
      patients with primary soft tissue sarcomas (STS) arising from the
      retroperitoneum. PATIENTS AND METHODS: One hundred and seventeen consecutive
      patients, resected in our institutions between July 1972 and November 2002, were
      reviewed. RESULTS: The prognostic factors predicting survival were incomplete
      resection, a tumor of high grade (G3), metastases to lymph nodes and distant
      metastasis. Patients with a malignant fibrous histiocytoma (MFH) or a malignant
      peripheral nerve sheath tumor (MPNST) had a worse prognosis than those patients
      with other tumors. The prognostic factors predicting local recurrence were
      incomplete resection and high grade (G3). The prognostic factors predicting
      metastasis were incomplete resection, lymph node metastasis at the time of the
      resection of the primary tumor and tumor histology. CONCLUSION: Since only
      complete tumor resection offers a chance for cure, it is mandatory, and local
      control remains the most significant challenge in the management of
      retroperitoneal sarcomas. Other therapies can support surgical treatment,
      depending on the tumor localization and histological entity. The management of
      patients with a STS should be provided by a specialized team of surgeons,
      oncologists and radiotherapists, and patients should be enrolled in a treatment
      study whenever possible.

PMID- 16619575
TI  - Enhanced expression of heat shock protein 27 following neoadjuvant hormonal
      therapy is associated with poor clinical outcome in patients undergoing radical
      prostatectomy for prostate cancer.
AB  - BACKGROUND: The objectives of this study were to characterize changes in the
      expression of heat shock protein 27 (HSP27) in prostate cancer before and after
      androgen withdrawal therapy and to assess the prognostic significance of HSP27
      expression in patients undergoing radical prostatectomy (RP) following
      neoadjuvant hormonal therapy (NHT). MATERIALS AND METHODS: This study included 97
      patients with clinically localized prostate cancer who received NHT followed by
      RP. Paired needle biopsy and corresponding RP specimens obtained from these
      patients were analyzed for expression of the HSP27 protein by immunohistochemical
      staining. These findings were evaluated with respect to several
      clinicopathological factors. RESULTS: HSP27 expression in the RP specimens
      following NHT was significantly up-regulated compared with that in the
      corresponding needle biopsy specimens. The expression level of HSP27 in the
      biopsy specimens was significantly associated with the biopsy Gleason score, but
      not with other factors available before RP. HSP27 expression in the RP specimens
      was significantly correlated with the pre-operative value of serum prostate
      specific antigen and pathological stage, but not with other pathological factors.
      Biochemical recurrence-free survival in patients with strong HSP27 expression in
      the RP specimens was significantly lower than that in those with weak HSP27
      expression; however, the expression level of HSP27 was not an independent
      predictor of biochemical recurrence. CONCLUSION: Despite the lack of independent
      significance, the expression level of HSP27 in prostate cancer tissue after NHT,
      which may inversely reflect the therapeutic effect of NHT, could be a useful
      parameter predicting biochemical recurrence in patients undergoing RP.

PMID- 16619576
TI  - MMP-9 and cathepsin B expression in tumor budding as an indicator of a more
      aggressive phenotype of colorectal cancer (CRC).
AB  - BACKGROUND: The aim of this study was to clarify the relationship between the
      expression of MMP-9 and Cathepsin B (CathB) at the main tumor mass and lymph node
      metastases and the presence of tumor budding and vascular invasion at the
      invasion front, as well as lymph node involvement. PATIENTS AND METHODS: The
      immunohistochemical expressions of MMP-9 and CathB were studied in 55 specimens
      of colorectal adenocarcinomas (pT3, G2). A standard avidin-biotin
      immunoperoxidase staining method (ABCu-NCL) was performed on 4-microm paraffin
      embedded tissue sections with a mouse anti-human MMP-9 and CathB monoclonal
      antibody. RESULTS: Positive immunostaining for MMP-9 in the primary tumor was
      observed in 30/55 (54.6%) cases and in 29 cases (52.7%) for CathB. A
      statistically significant association was found between the expressions of MMP-9
      and CathB in the primary tumor and lymph node involvement (p<0.01). The
      expression of CathB in the primary tumor was associated with the presence of
      tumor budding and vascular invasion (p<0.01); but no such association was found
      for MMP-9. The expressions of MMP-9 and CathB in buds were strongly associated
      with lymph node involvement (p<0.01). However, the presence of vascular invasion
      was significantly associated only with positive expression of CathB in the buds
      (p<0.01). CONCLUSION: If the presence of budding in the colorectal cancer
      invasive front indicates higher invasive potential, the present results seem to
      suggest the existence of a strong relationship between MMP-9 and CathB
      expressions in the buds and a more aggressive tumor phenotype.

PMID- 16619577
TI  - Feasibility study of biweekly CPT-11 plus CDDP for S-1- and paclitaxel
      refractory, metastatic gastric cancer.
AB  - BACKGROUND: To confirm the feasibility and efficacy of biweekly irinotecan (CPT
      11) plus cisplatin (CDDP) as third-line chemotherapy, the response rate (RR),
      overall survival and toxicity were evaluated in patients who had been treated
      with S-1 as a first-line and paclitaxel as a second-line chemotherapy for
      metastatic gastric cancer. PATIENTS AND METHODS: The eligibility criteria of our
      study were: i) pathologically-confirmed adenocarcinoma of the stomach, ii)
      primary non-resectable or recurrent tumors, iii) Eastern Cooperative Oncology
      Group (ECOG) performance status (PS) of 2 or less, iv) age less than 75 years, v)
      adequate hepatic, renal and bone marrow functions and vi) patients had received S
      1 as a first-line and paclitaxel as a second-line chemotherapy and both regimens
      had failed. The treatment consisted of CPT-11 (60 mg/m2) and CDDP (30 mg/m2) on
      day 1 and day 15, repeated every 4 weeks. RESULTS: Twenty-six patients were
      enrolled in this study. All the treatment was administered at the out-patient
      clinic except the first course for the initial 4 patients. The overall RR was
      23.1% in all and 30.0% in the patients with target tumors (6 partial response, 11
      stable disease, 7 progressive disease, 2 non-evaluable). Overall grade 3/4
      toxicity was observed in 5 patients (19.2%) including pancytopenia, neutropenia,
      anemia, anorexia and elevation of AST/ALT. The time-to-treatment failure and the
      median survival time were 95 and 299 days, respectively. CONCLUSION: Biweekly CPT
      11 plus CDDP was feasible for S-1- and paclitaxel-refractory metastatic gastric
      cancer, with moderate activity and favorable toxicity. This regimen was safely
      performed at the out-patient clinic as third-line chemotherapy.

PMID- 16619578
TI  - Iodine-123 metaiodobenzylguanidine scintigraphy in localising phaeochromocytomas-
      experience and meta-analysis.
AB  - BACKGROUND: Recommendations on the use of I-123 metaiodobenzylguanidine (MIBG)
      scintigraphy in localising phaeochromocytomas vary. The accuracy of I-123 MIBG
      scintigraphy was determined by evaluating our own I-123 MIBG scans and performing
      a meta-analysis. MATERIALS AND METHODS: Between January 1992 and May 2002, the I
      123 MIBG scans of consecutive patients suspected of a phaeochromocytoma were re
      evaluated. For the meta-analysis, studies with more than 5 I-123 MIBG scans were
      selected. RESULTS: Thirty patients were evaluated. The sensitivity in our own
      population was 92% and the specificity was 100%. Twelve articles were selected
      for our meta-analysis. The overall sensitivity and specificity were 96% and 100%,
      respectively. The sensitivity and specificity for tumours in the adrenal gland
      was 98% for both. For tumours located outside the adrenal gland, the sensitivity
      was 98% and the sensitivity for malignancies was 79%. CONCLUSION: 1-123 MIBG
      scintigraphy has an excellent sensitivity and specificity in localising
      phaeochromocytomas, except for malignant tumours. 1-123 MIBG scintigraphy is
      superior in localising tumours outside the adrenal gland.

PMID- 16619579
TI  - A phase I study of S-1 administration and a 24-h infusion of cisplatin plus
      paclitaxel in patients with advanced gastric cancer.
AB  - OBJECTIVE: The objective of this study was to determine the dose-limiting
      toxicity (DLT), the maximum tolerated dose (MTD), the recommended dose (RD) and
      the preliminary antitumor activity of S-1, oral dihydropyrimidine dehydrogenase
      inhibitory fluoropyrimide, in combination with cisplatin and paclitaxel for
      advanced gastric cancer. PATIENTS AND METHODS: Paclitaxel was administered on day
      1. A fixed dose of S-1 (70 mg/m2/day) was orally administered for 14 consecutive
      days from day 1 and a 24-h infusion of a fixed dose of cisplatin (60 mg/m2) was
      administered on day 14 of every 28-day cycle. Four dose escalation levels of
      paclitaxcel were studied (120, 140, 160 and 180 mg/m2). RESULTS: Twenty patients
      were enrolled. The toxicities were generally mild no grade 4 hematological
      toxicity or grade 3 non-hematological toxicity were observed. Level 4 was
      considered as the MTD because of a treatment delay of more than 2 weeks in 3 out
      of 6 patients. The RD of paclitaxcel was 160 mg/m2. The overall response rate was
      75%. CONCLUSION: A triple combination chemotherapy consisting of S-1, cisplatin
      and paclitaxel showed a tolerable level of adverse reactions and favorable
      antitumor activity.

PMID- 16619580
TI  - Activating Gs a mutation rarely occurs in musculoskeletal tumors other than
      fibrous dysplasia.
AB  - BACKGROUND: Activating Gs a mutations have been identified in most instances of
      fibrous dysplasia (FD). This mutation leads to consistently elevated
      intracellular cyclic adenosine monophosphate (cAMP) levels, with various
      biological consequences. The development of secondary sarcoma in FD is a rare but
      well-established phenomenon. This finding raised the possibility that a common
      gene mutation exists in these tumors. MATERIALS AND METHODS: The expression of
      the Gs a mutation was examined in 16 cell lines and 173 musculoskeletal tumor
      tissues, including 13 cases of FD, via RT-PCR and sequence analysis. RESULTS: No
      expression of a Gs a mutation was detected in any cell line or clinical tissue
      sample, excluding FD tissues. Direct sequence analysis demonstrated results
      identical to those of RT-PCR. CONCLUSION: Activating Gs a mutation rarely occurs
      in musculoskeletal tumors other than FD. The occurrence of most sarcomas displays
      no correlation with Gs a mutations.

PMID- 16619581
TI  - High expression of Jun activation domain-binding protein 1 (Jab1) is a strong
      prognostic marker in oral squamous cell carcinoma patients treated by UFT in
      combination with radiation.
AB  - Low expression of p27Kip1 is associated with disease progression and an
      unfavorable outcome in several malignancies, including oral squamous cell
      carcinoma (OSCC). In addition, the p27Kip1 protein is thought to be degraded by
      the Jun activation domain-binding protein 1 (Jab1). The purpose of this study was
      to examine whether Jab1 expression can be a useful prognostic factor in OSCC
      patients treated by 1 M Tegafur and 4 M uracil (UFT) in combination with
      radiation. Jab1 expression was investigated by immunohistochemistry in biopsy
      samples from 102 OSCC patients who were treated by UFT in combination with
      radiation. The associations of each expression with the clinicopathological
      characteristics and patient survival were also analyzed. A significant
      association was found between Jab1 expression and cervical lymph node metastasis
      (p=0.0004), stage of disease (p=0.0011), therapeutic effect (p=0.0133) and
      patient outcome (p=0.0095). The 5-year survival rates of Jab1 high- and low
      expression tumors were 53.0% and 80.6%, respectively and this difference was
      significant (p=0.0053) by the log-rank test. Multivariate analysis revealed that
      reduced term survival was related to high levels of Jab1 expression (p=0.0082).
      These results suggest that Jab1 may be a useful prognostic factor in OSCC
      patients treated by UFT in combination with radiation.

PMID- 16619582
TI  - Diffuse micronodular pulmonary metastasis of lung adenocarcinoma predicts
      gefitinib response in association with epidermal growth factor receptor
      mutations.
AB  - Female, non-smoker, Asian ethnicity and adenocarcinoma histology are the major
      clinical predictors of gefitinib response in non-small cell lung cancer, as shown
      in previous studies. Recently, response to gefitinib has been associated with
      epidermal growth factor receptor (EGFR) mutations. Higher rates of mutation were
      seen in females, patients with adenocarcinomas, the Asian population and never
      smokers, which may explain the clinical response predictors. The presence of
      diffuse micronodular pulmonary metastasis on chest imaging as a novel clinical
      predictor of its response is proposed here. Two cases of lung adenocarcinomas in
      men presenting with diffuse micronodular pulmonary metastasis were encountered.
      Both patients showed a major response to gefitinib. The dramatic reduction of
      micronodular pulmonary nodules throughout both lungs on computed tomography scans
      was achieved after treatment for a couple of months with 250 mg of oral
      gefitinib. In the molecular analysis, one patient had a heterozygous delL746-A750
      mutation and the other had a heterozygous L858R EGFR mutation. In conclusion,
      patients with lung adenocarcinoma, even men, who presented with bilateral diffuse
      micronodular metastatic spread to the lungs tended to have an activated EGFR
      mutation. Therefore, they are most likely to receive benefits from molecular
      target drugs such as gefitinib and possibly erlotinib.

PMID- 16619583
TI  - Long-term control of bone marrow carcinosis and severe thrombocytopenia with
      standard-dose chemotherapy in a breast cancer patient: a case report.
AB  - BACKGROUND: Primary metastatic breast cancer with bone marrow involvement and
      pronounced thrombocytopenia is rare. The myelosuppressive effect of most
      cytotoxic drugs limits chemotherapy in patients with cytopenia due to marrow
      involvement. CASE REPORT: A 62-year-old patient, who presented with locally and
      systemically advanced breast cancer, is reported. The initial work-up revealed
      bone marrow carcinosis with thrombocytopenia of less than 20,000/mm3 lung and
      osseous metastases without signs of suppressed erythropoiesis and leucopoiesis.
      The patient was stabilized with 6 different standard-dose chemotherapy regimens,
      antihormonal therapy, and trastuzumab before dying 57 months after first
      diagnosis. The patient received only platelet transfusions on 2 instances with
      platelets of 2,000/mm3. CONCLUSION: This case illustrates that aggressive
      standard chemotherapy may be feasible in selected patients with bone marrow
      carcinosis-associated thrombocytopenia without major bleeding episodes.

PMID- 16619584
TI  - A pilot study of combination chemotherapy with S-1 and low-dose cisplatin for
      highly advanced gastric cancer.
AB  - BACKGROUND: The surgical outcome for advanced gastric cancer, even following
      curative surgery, is associated with a poor prognosis. A pilot study in advanced
      gastric cancer patients was carried out using pre-operative chemotherapy with S-1
      and low-dose cisplatin (CDDP) (TSLD). PATIENTS AND METHODS: Twenty-one patients
      with stage IV gastric cancer were treated with TSLD as the initial treatment,
      after informed consent had been obtained. Surgery was performed when curative
      resection was deemed feasible in selected patients who showed improvement in
      their tumors. Other regimens including CPT-11 or taxanes were utilized as second
      line chemotherapy when the tumor showed no change or progressive disease
      following TSLD therapy. RESULTS: No patient had a complete response, while 11 had
      partial responses following TSLD therapy, yielding an overall response rate of
      52.4%. Fifteen out of 21 (71.4%) underwent surgery following TSLD therapy, while
      curative surgery determined by histological investigation was performed in 10 out
      of 15 (47.6%) patients. No grade 4 toxicities or treatment-related deaths were
      observed. The following grade 3 toxicities were observed: neutropenia (6
      patients), thrombocytopenia (1 patient) and anemia (1 patient). The other
      toxicities observed, including gastrointestinal toxicity, were grade 2 or less.
      The median survival time of all patients was 526 days, and 1- and 2-year survival
      rates were 64.9% and 41.7%, respectively. CONCLUSION: TSLD is a potent regimen
      with a low toxicity profile for highly advanced gastric cancer.

PMID- 16619585
TI  - Influence of altering administration sequence of docetaxel, gemcitabine and
      cisplatin in patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: A phase II study of a triplet chemotherapy with the administration
      sequence of gemcitabine (GEM), docetaxel (DCT) and cisplatin (CDDP) (OLCSG9908)
      was previously conducted in patients with advanced non-small cell lung cancer
      (NSCLC). The objective response rate was 34% and the median survival time (MST)
      and 1-year survival rate were 11.7 months and 49%, respectively. In an in vitro
      study of different sequence exposures to GEM and DCT, it was reported that the
      synergistic effect was more prominent using the administration sequence of DCT
      followed by GEM compared with the reverse sequence. In order to estimate the
      effects of the administration sequence, a phase II study of the same triplet
      chemotherapy was conducted with the administration sequence of DCT, CDDP and GEM.
      PATIENTS AND METHODS: Patients with unresectable stage IIIB/IV NSCLC were
      eligible. All drugs were given intravenously on days 1 and 8, and repeated every
      4 weeks for up to 4 cycles. DCT (30 mg/m2) was given first, followed by CDDP (40
      mg/m2) and GEM (800 mg/m2). RESULTS: Thirty-four patients were enrolled on this
      study (OLCSG0101). The objective response rate was 38% (95% CI: 22-56%). As grade
      3/4 hematological toxicities, neutropenia, thrombocytopenia and anemia were
      observed in 70%, 41% and 21%, respectively, and febrile neutropenia was observed
      in 12%. As grade 3/4 non-hematological toxicities, vomiting and liver dysfunction
      were observed in 15% and 18%, respectively. These toxicities were manageable by
      conventional therapy. The MST and 1-year survival rate were 13.3 months (95% CI:
      7.8-18.7 months) and 55% (95% CI: 38-73%), respectively. These results were
      similar to those of OLCSG9908. CONCLUSION: This triplet chemotherapy is well
      tolerated and effective in patients with advanced NSCLC, however, the treatment
      outcome was not significantly influenced by the administration sequence of DCT
      and GEM.

PMID- 16619586
TI  - PTPN3 and PTPN4 tyrosine phosphatase expression in human gastric adenocarcinoma.
AB  - BACKGROUND: Degenerated PCR primers, designed according to the consensus tyrosine
      phosphatase catalytic motifs, were used in order to amplify expressed protein
      tyrosine phosphatase molecules from human gastric cancer-derived cells. From such
      profiles, more than twenty different types of tyrosine phosphatase were
      identified from gastric cancer tissue. A non-receptor tyrosine phosphatase,
      PTPN4, was found to be expressed in a tumor-tissue profile with only low
      frequency. The most closely-related gene to tyrosine phosphatase, PTPN3, has been
      shown to be mutated in cases of human colorectal cancer, but its expression is
      cases of gastric cancer is not known. MATERIALS AND METHODS: The mRNA expression
      of PTPN3 and PTPN4 by RT-PCR was investigated, and the protein expression status
      of PTPN3 was examined, using immunohistochemistry, to elucidate
      clinicopathological associations of the PTPN3 and PTPN4 family within human
      stomach cancer. RESULTS: PTPN3 and PTPN4 were expressed in all gastric cancer
      cell lines and clinical cancer tissue specimens examined. Following the
      examination of 92 gastric cancer patients' pathological specimens, PTPN3
      expression showed no statistical significance with respect to the patients'
      survival. A statistically significant correlation between PTPN3 staining and the
      differentiation status of gastric cancer tissue was, however, observed.
      CONCLUSION: This finding indicates that both PTPN3 and PTPN4 are expressed within
      human gastric cancer cells and that PTPN3 seems to play an important role in
      gastric cancer differentiation and the progression of malignancy.

PMID- 16619587
TI  - Ex vivo chemosensitivity of head and neck carcinoma to cytostatic drug
      combinations.
AB  - Previous studies focusing on response prediction to chemotherapy by
      chemosensitivity testing of tumor explants has focused on the response
      determination of single cytostatic drugs, in contrast to the common clinical
      application of cytostatic drug combinations. Therefore, the present study was
      aimed at determining the quantitative ex vivo chemoreactivity of epithelial cells
      from head and neck squamous cell carcinoma (HNSCC) specimens to cytostatic drug
      combinations. Specimens from 12 histologically-confirmed HNSCC were investigated.
      According to a previously established ex vivo colony formation assay, the
      individual cellular chemoreactivity was determined quantitatively for
      combinations of 4 cytostatic drugs: cis-platinum (cis-DDP), carboplatin (CBDCA),
      5-Fluorouracil (5-FU) and docetaxel (DTX). The tests were performed using drug
      combinations according to recent clinical therapy regimens in the treatment of
      solid tumors: i) cis-DDP + 5FU, ii) CBDCA + 5FU, iii) cis-DDP + DTX and iv) CBDCA
      + DTX. The approach provides individual drug response patterns of epithelial as
      well as of stromal cells. Individual, selective sensitivities were found for each
      drug combination tested. The stromal and epithelial chemoreactivity profiles
      differed in most of the specimens. Moreover, stromal cell chemoresistance
      dominated selective epithelial chemosensitivities in the majority of cases. The
      determination of the epithelial ex vivo chemoreactivity identified individual
      chemosensitivities which were verified by the clinical history of the patient.
      Therefore, the described protocol to determine the ex vivo chemoresponse of HNSCC
      specimens to cytostatic drug combinations may help to provide clinicaly useful
      information concerning the individual chemoresponse of HNSCC with regard to
      individualization of oncological decision making.

PMID- 16619588
TI  - Expression of p27KIP1, p21WAF1 and p53 does not correlate with prognosis in node
      negative invasive ductal carcinoma of the breast.
AB  - The expressions ofp27Kip1 (p27) and p21waf1 (p21) cyclin-dependent kinase
      inhibitors and p53 were examined in a series of 170 node-negative breast
      carcinomas (NNBCs) to evaluate their prognostic significance. Low nuclear (p27TN)
      and cytoplasmic (p27TC) p27 expressions were noted in 66% and 81% of NNBCs,
      respectively. p21 and p53 overexpressions were detected in 56% and 26%,
      respectively. Low p27TN was significantly associated with high grade (p=0.001),
      age < or = 50 years (p=0.01), negative hormone receptors (p<0.001), low p27TC
      (p<0.001) and p53 overexpression (p=0.02). Low p27TC was associated with negative
      hormone receptors (p<0.001). p53 overexpression was associated with high grade
      (p<0.001) and negative hormone receptors (p<0.001). p21 overexpression, although
      not correlated with the examined parameters, was associated with increased
      disease-free survival in univariate analysis. In multivariate analysis, p27TN,
      p27TC, p21 and p53 were not associated with disease-free survival or overall
      survival. These findings argue against the prognostic value of p27, p21 and p53
      in NNBC.

PMID- 16619590
TI  - Whartonia (Fascutonia) natsumei (Acari: Trombiculidae): a new bat chigger
      collected from Plecotus auritus (Chiroptera: Vespertilionidae) in Japan, with
      host and distribution records of the genus Whartonia.
AB  - We describe and illustrate a new bat chigger, Whartonia (Fascutonia) natsumei
      Takahashi, Takahashi & Kikuchi n. sp., ex. Plecotus auritus (Linnaeus, 1758),
      from Japan, and summarize the host and distribution records of the chiggers of
      the genus Whartonia Ewing, 1944. With the description of a new species here, the
      number of Whartonia species increases to 40 composed of 22 species from Asia, 14
      from North and South America in addition to Central America, and four from
      Africa.

PMID- 16619589
TI  - Salvage treatment with single-agent capecitabine in patients with heavily
      pretreated advanced colorectal cancer.
AB  - BACKGROUND: Refractory and/or relapsing advanced colorectal cancer (ACRC)
      requires frequent and prolonged hospitalisations, with a negative impact on the
      patients' quality of life (QoL). The aim of this single-centre, phase II study
      was to investigate the efficacy and safety of capecitabine (C) as salvage therapy
      in patients (pts) with ACRC, heavily pretreated with various chemotherapeutic
      regimens, as well as radiotherapy. PATIENTS AND METHODS: A total of 28 pts were
      enrolled, with the following characteristics: 16 male and 12 female, median age
      60 years (36-70) and median ECOG PS 1 (0-2). All pts had previously received at
      least 2 regimens of standard chemotherapy, including 5-FU/leucovorin, oxaliplatin
      and irinotecan in various combinations, while 8 pts had been offered
      radiotherapy. Four pts had already been treated with C. The treatment was
      administered at home and consisted of C at a dose of 1250 mg/m2 twice daily on
      days 1-14, every 3 weeks, until disease progression (PD) and for a maximum of 9
      cycles. Since grade (G) 3 gastrointestinal (GI) toxicity was observed among the
      first 7 pts, a daily dose of 2 g/m2 was adopted in the subsequent enrolment.
      RESULTS: The disease control (DC) rate was 53% (95% CI: 33.8%-72.5%): partial
      response in 2 pts and disease stabilization in 13 pts. Three out of 4 pts
      previously exposed to C showed stable disease. A significant symptom improvement
      was demonstrated in all 4pts with non-measurable baseline disease. The median
      time to progression was 4 months (range: 2-7). Nine pts had PD while on
      treatment. The median overall survival times for pts with DC and PD were 6 months
      and 3 months, respectively. Various types of G3 haematological toxicity were
      observed in 4/28 pts, G3 hand-foot syndrome in 6/28 pts and G3 GI toxicity in
      8/28 pts. Nevertheless, the patients' QoL and the regimen's safety profile were
      satisfactorily preserved. CONCLUSION: Despite its methodological limitations, our
      trial suggests that salvage treatment of heavily pretreated ACRC with single
      agent C may be considered a safe and cost-effective alternative to best
      supportive care.

PMID- 16619591
TI  - Establishment of Ochlerotatus japonicus (Diptera: Culicidae) in Ontario, Canada.
AB  - Ochlerotatus (Finlaya) japonicus (Theobold) is newly established in Ontario,
      Canada. It was first discovered in 2001 during the province-wide West Nile virus
      mosquito surveillance program implemented by the Ontario Ministry of Health and
      Long Term Care. Although the numbers of adults trapped in CDC light traps were
      low in 2001 and 2002, they increased during the 2003 and 2004 surveillance
      seasons. Oc. japonicus larvae also have been collected in large numbers in the
      Niagara Peninsula in a variety of natural and artificial containers. The number
      of health units with records for Oc. japonicus has increased over the 4 yr of
      surveillance, illustrating the ability of this species to rapidly extend its
      range. As a potential arboviral bridge vector, its establishment in Ontario
      requires further study and should be considered a public health concern.

PMID- 16619592
TI  - Flight initiation of Triatoma infestans (Hemiptera: Reduviidae) under natural
      climatic conditions.
AB  - Flight dispersal of Triatoma infestans Klug is probably the most important
      mechanism for house reinfestation at a village scale after residual spraying with
      insecticides. The aim of the current study was to estimate the flight initiation
      probability of field-collected T. infestans and to assess how this probability
      was affected by sex, adult age, partial bloodmeal, and the presence of a host
      inaccessible for feeding. Four experimental series, each consisting of three to
      six consecutive nights and repeated measurements of flight initiation on each
      individually marked bug, were carried out in experimental huts inside closed
      cages under natural climatic conditions. We demonstrate that flight initiation
      probability of T. infestans is much higher than previously reported, responds to
      temperature in a sigmoid manner, and is higher in females than males, and that
      the frequency distribution of the number of flights per individual is highly
      aggregated in female and male bugs. The age of adults had strong effects on
      flight initiation, whereas the presence of an inaccessible host and a partial
      bloodmeal exerted no significant effects in models controlling for the effects of
      bug weight-to-length ratio. The high flight potential found is consistent with
      the rapid changes in reinfestation patterns observed in the field. The present
      estimates of flight probabilities and the identification of factors modifying
      them provide essential knowledge for modeling reinfestation patterns and for
      improving control strategies of T.

PMID- 16619593
TI  - Targeted trapping of mosquito vectors in the Chesapeake Bay area of Maryland.
AB  - Most adult mosquito surveillance in Maryland is performed using dry ice-baited or
      unbaited Centers for Disease Control (CDC) miniature light traps suspended
      approximately 1.5 m above the ground. However, standardized trapping methods may
      miss mosquito species involved in disease transmission cycles. During a 2-yr
      study, the effectiveness of the olfactory attractant 1-octen-3-ol alone and in
      combination with carbon dioxide was evaluated for collecting mosquito vector
      species. In addition, trap heights were examined to determine the optimal
      vertical placement to target various species. We evaluated the results during the
      second year by targeting selected species by using various habitat- height-bait
      combinations. Although Culex erraticus Dyar & Knab and Anopheles quadrimaculatus
      Say were not successfully targeted, Culex salinarius Coquillett, Aedes vexans
      Meigen, Anopheles bradleyi/crucians King, Coquillettidia perturbans Walker, Aedes
      sollicitans Walker, and Aedes taeniorhynchus Wiedemann were preferentially
      captured using targeted trapping schemes.

PMID- 16619594
TI  - Borrelia lusitaniae and spotted fever group rickettsiae in Ixodes ricinus (Acari:
      Ixodidae) in Tuscany, central Italy.
AB  - Prevalence of infection by Borrelia burgdorferi s.l. and spotted fever group
      (SFG) rickettsiae was estimated in host-seeking ticks in an area in Tuscany,
      central Italy, where Lyme borreliosis was reported in a forestry worker. B.
      burgdorferi s.l. was identified by polymerase chain reaction in 16.7% (95% CI =
      10.3, 24.8) of Ixodes ricinus (L.) nymphs and 39.6% (95% CI = 26.5, 54.0) of
      adults. Borrelia lusitaniae accounted for 82.9% of positive samples, followed by
      Borrelia garinii (9.8%), Borrelia afzelii (2.4%), and Borrelia burgdorferi s.s.
      (2.4%). One Rhipicephalus spp. adult was infected with B. garinii (prevalence =
      8.3%; 95% CI = 0.21, 38.5). Prevalence of infection by SFG rickettsiae was 38.5%
      (95% CI = 26.7, 51.4) in I. ricinus nymphs, 34.6% (95% CI = 22.0, 49.1) in I.
      ricinus adults, and 50% (95% CI = 21.1, 78.9) in Rhipicephalus spp. adults.
      Phylogenetic analysis showed the similarity of B. lusitaniae strains that were
      identified in this study and of a strain that was previously isolated from a
      human patient in Portugal. Results of this study confirm the dominance of B.
      lusitaniae in areas in the Mediterranean basin and the infection by SFG
      rickettsiae in I. ricinus.

PMID- 16619595
TI  - Spatiotemporal patterns of host-seeking Ixodes scapularis nymphs (Acari:
      Ixodidae) in the United States.
AB  - The risk of Lyme disease for humans in the eastern United States is dependent on
      the density of host-seeking Ixodes scapularis Say nymphal stage ticks infected
      with Borrelia burgdorferi. Although many local and regional studies have
      estimated Lyme disease risk using these parameters, this is the first large-scale
      study using a standardized methodology. Density of host-seeking I. scapularis
      nymphs was measured by drag sampling of closed canopy deciduous forest habitats
      in 95 locations spaced among 2 degrees quadrants covering the entire United
      States east of the 100th meridian. Sampling was done in five standardized
      transects at each site and repeated three to six times during the summer of 2004.
      The total number of adults and nymphs of the seven tick species collected was
      17,972, with 1,405 nymphal I. scapularis collected in 31 of the 95 sites. Peak
      global spatial autocorrelation values were found at the smallest lag distance
      (300 km) and decreased significantly after 1,000 km. Local auto-correlation
      statistics identified two significant high-density clusters around endemic areas
      in the northeast and upper Midwest and a low-density cluster in sites south of
      the 39th parallel, where only 21 nymphs were collected. Peak nymphal host-seeking
      density occurred earlier in the southern than in the most northern sites.
      Spatiotemporal density patterns will be combined with Borrelia prevalence data as
      part of a 4-yr survey to generate a nationwide spatial risk model for I.
      scapularis-borne Borrelia, which will improve targeting of disease prevention
      efforts.

PMID- 16619596
TI  - Impact of trap elevation on estimates of abundance, parity rates, and body size
      of Culex pipiens and Culex restuans (Diptera: Culicidae).
AB  - Trapping success, abundance, parity rate, and body size indices of Culex pipiens
      (L.) and Culex restuans Theobald, important vectors of West Nile virus (family
      Flaviviridae, genus Flavivirus, WNV), were determined for specimens captured from
      both ground level (approximately 1-m) and elevated (approximately 6- to 7-m) CO2
      baited CDC miniature light traps. Mosquitoes were collected from six study sites
      in Albany County, New York, from mid-May to mid-October 2004. There was no
      significant difference in abundance or mean parity for either Cx. pipiens or Cx.
      restuans between the elevated and the ground-level traps. Mosquitoes collected in
      elevated traps tended to be larger than mosquitoes collected at ground level.
      Elevated traps captured significantly fewer mosquitoes per trap-night than did
      ground traps, but a greater proportion of those captured were Culex spp.
      Therefore, elevated traps more efficiently captured Cx. pipiens and Cx. restuans
      with similar reproductive status and body size and reduced the time necessary to
      sort and identify collections. These findings may be beneficial to researchers or
      surveillance programs focusing on Cx. pipiens or Cx. restuans.

PMID- 16619597
TI  - Natural survivorship of immature stages of Culex vishnui (Diptera: Culicidae)
      complex, vectors of Japanese encephalitis virus, in rice fields in southern
      India.
AB  - The development and survival of immatures of Culex vishnui (Diptera: Culicidae)
      complex, vectors of Japanese encephalitis virus, were studied in transplanted
      rice, Oryza savita L., fields during three crop growing seasons. The total
      duration of development from the first instar to adult emergence varied from 6 to
      8 d. Survival rate estimates ranged from 0.003 to 0.524, but they generally were
      <0.1. Unusually high survival rates (0.192-0.524) were observed in summer and
      long-term monsoon crop seasons during 1993. A multiple regression method using
      backward elimination was used to analyze the factors responsible for these
      variations. The model identified nine parameters related with survival rates that
      explained 99% of the variance. Area of water surface and hardness were negatively
      related, whereas green algae, notonectid adults, anisopterans, dytiscids,
      salinity, water depth, and dissolved oxygen were positively associated with
      immature survival.

PMID- 16619598
TI  - Life history and seasonal abundance of Fannia benjamini complex (Diptera:
      Muscidae) in southern California.
AB  - Seasonal abundance and life history of Fannia benjamini complex (Diptera:
      Muscidae) was studied in the coastal mountain community ofLa Habra Heights in Los
      Angeles County, California, with additional observations in drier, inland
      mountains in the Woodcrest area, Riverside County. The dominant species (>95% of
      fly collections) was Fannia conspicua Malloch, whereas Fannia benjamini Malloch
      also was present. Both species could be collected nearly year-round by netting
      adults (almost exclusively females) attracted to people, although F. benjamini
      was relatively more common in cooler weather (November-April). In La Habra
      Heights, adult activity peaked in June and July (both species), whereas peak
      activity in Woodcrest was late April through June for F. conspicua and February
      through April for F. benjamini. Field-collected adult females provided only water
      died within 2-4 d, whereas females provided with water plus a dry milk and sugar
      mixture survived up to 128-130 d in the laboratory. Males of F. conspicua (1-40
      individuals) swarmed at heights of 0.5-4.0 m near Aptenia cordifolia (L.f.)
      Schwantes, an exotic, succulent, low-growing ground cover plant. Eggs of F.
      conspicua were deposited singly on older, decaying leaves of this plant, and
      adult F. conspicua emerged from Aptenia-covered areas in the field. In the
      laboratory, larvae of F. conspicua grazed on microbial surface films associated
      with Aptenia. Emergence of F. conspicua from field-collected soil-Aptenia
      mixtures (held in the laboratory) occurred from 1.5 to 5 mo after collection.
      Widespread Aptenia planting since the 1980s has probably resulted in F. conspicua
      becoming a severe human nuisance in some areas.

PMID- 16619599
TI  - Population dynamics of malaria vectors in western Kenya highlands.
AB  - Studies were carried out at three sites in the highlands of western Kenya (Iguhu
      and Mbale in Kakamega and Vihiga districts, respectively, and Marani in Kisii
      district) and at one site in the western Kenya lowlands (Kombewa in Kisumu
      district) to determine the spatial-temporal dynamics of malaria vectors and
      intensity of malaria transmission from June 2003 to June 2004. At the highland
      sites, Anopheles gambiae Giles predominated, constituting >80% of the vector
      species, whereas An. funestus Giles made up <20%. In contrast, at the lowland
      site, An. funestus made up 68% of the vector species. The mean annual indoor
      resting densities of An. gambiae at Iguhu were 5.0 female mosquitoes per house
      per night, 14.2- and 26.3-fold greater than those at Mbale and Marani. During the
      main transmission season, the indoor resting densities of An. gambiae increased
      4.1-, 10.1-, and 5.0-fold over the dry season period in Iguhu, Mbale, and Marani,
      respectively. The estimated annual entomological inoculation rate (EIR) at Iguhu
      was 16.6 infectious bites per person per year (ib/p/yr), 1.1 at Mbale, and 0.4 at
      Marani. This suggests high spatial variation in vector abundance and malaria
      transmission intensity. At the lowland site, Kombewa, the total annual EIR was
      31.1 ib/p/yr and the indoor resting densities during the transmission season
      increased 7.1-fold in An. funestus and 18.5-fold in An. gambiae sensu lato over
      the dry season. The low level of transmission in the highlands suggests that it
      may be disrupted by vector control methods such as residual spraying.

PMID- 16619600
TI  - Electroantennogram and behavioral responses of Culex quinquefasciatus (Diptera:
      Culicidae) females to chemicals found in human skin emanations.
AB  - The southern house mosquito, Culex quinquefasciatus Say (Diptera: Culicidae), is
      closely associated with humans and is a vector of filariasis. Use of
      semiochemicals for control of mosquitoes is a novel and potentially ecofriendly
      control approach. Human skin emanations are known to attract mosquitoes. In the
      current study, olfactory and behavioral responses of host-seeking female Cx.
      quinquefasciatus to various chemical components of human skin emanations
      (carboxylic acids, alcohols, and aldehydes) were evaluated separately at three
      doses (0.01, 0.1, and 1 microg) for electroantennogram (EAG) and three doses
      (0.1, 1, and 10 microg) for behavioral assay. Results of EAG studies indicated
      that all carboxylic acids elicited significant olfactory responses except
      tetradecanoic acid (C14) and octadecanoic acid (C18). In particular, hexanoic
      acid (C6) elicited a maximum, eight-fold olfactory response compared with the
      solvent control. Ethylene glycol and benzyl alcohol exhibited significant EAG and
      behavioral responses, whereas among aldehydes, nonanal elicited high EAG and
      behavioral responses, but only at all three doses tested compared with control.
      Some carboxylic acids elicited significant behavioral responses, attracting
      approximately 75% of females tested toward chemical stimuli in a Y-tube
      olfactometer.

PMID- 16619601
TI  - Characteristics of grass infusions as oviposition attractants to Aedes
      (Stegomyia) (Diptera: Culicidae).
AB  - Ovitraps baited with grass infusions were evaluated in the field as oviposition
      attractants or stimulants for Aedes (Stegomyia) mosquitoes. Significantly higher
      oviposition by Aedes aegypti (L.) was observed in areas with no vegetation, but
      intense human presence, whereas Aedes albopictus (Skuse) oviposition was
      significantly higher in areas with vegetation, regardless of human presence.
      Ovitraps baited with infusions of Panicum maximum (Jacq.) collected significantly
      more eggs than controls containing tap water. Moreover, the number of eggs
      deposited in ovitraps baited with infusion made from fresh, mature leaves was
      higher compared with dried leaves or fresh, immature leaves. Anaerobically
      fermented of grass infusions were more attractive than either aerobically
      fermented or sterilized infusions of P. maximum. The fermentation age of the
      grass infusion also affected the oviposition response of mosquitoes.
      Significantly more eggs were deposited in baited ovitraps containing a fresh leaf
      infusion of P. maximum fermented for 15 or 20 d, compared with the controls. This
      demonstrates that 15- or 20-d anaerobic fermentation made of fresh, fully mature
      leaves of P. maximum is the optimum infusion for ovitrap-based Aedes (Stegomyia)
      surveillance mosquitoes in Brazil. Neglecting to consider these differences in
      infusion attractiveness may introduce significant variation in surveillance
      results.

PMID- 16619602
TI  - Effects of larval competitors and predators on oviposition site selection of
      Anopheles gambiae sensu stricto.
AB  - We examined whether predators and competitors influence selection of oviposition
      sites by Anopheles gambiae Giles. Mosquitoes in cages laid significantly fewer
      eggs in rainwater conditioned with a predator (backswimmers, Notonecta sp.) than
      in unconditioned rainwater. Rainwater conditioned with a putative competitor
      (tadpoles, Xenopus sp.) also had fewer eggs than unconditioned rainwater.
      Similarly, mosquitoes laid significantly fewer eggs in rainwater conditioned with
      five and 50 An. gambiae larvae than in unconditioned rainwater. When larvae were
      present, significantly more eggs were laid in containers with five larvae than in
      containers with higher densities, but the differences in number of eggs laid were
      not significant among the densities of 40, 70, and 100 larvae. This study
      demonstrated that caged An. gambiae females avoid oviposition in habitats with
      supposed competitors and predators.

PMID- 16619603
TI  - Laboratory evaluation of avian odors for mosquito (Diptera: Culicidae)
      attraction.
AB  - Attraction of Culex quinquefasciatus Say, Culex tarsalis Coquillett, Culex
      nigripalpus Theobald, and Aedes aegypti (L.) to avian and other host odors was
      investigated in a dual-port olfactometer. Although attraction to a human arm was
      high for Ae. aegypti (>80%) and low for all Culex spp. (<25%), all species
      responded similarly to a chicken (55.3-73.6%). Responses of Ae. aegypti, Cx.
      quinquefasciatus, and Cx. nigripalpus to feathers were low (<20%) but greater
      than to controls. There was no difference in attraction of Cx. tarsalis to
      feathers or controls. Responses to CO2 (5 ml/min) were low for all species (<15%)
      except Cx. tarsalis, which were moderate (24.5%). When feathers were combined
      with CO2, the resulting attraction was additive or lower than responses to
      feather and CO2 alone for all species except for Cx. tarsalis, which had
      responses that were three-fold greater than expected if responses were additive.
      The CO2-feather treatments were less attractive than a chicken for all species.
      When olfactometer assays were extended from 3 to 20 min, responses by Ae. aegypti
      significantly increased to a chicken and CO2 and attraction of Cx.
      quinquefasciatus significantly greater to chickens, CO2, and feathers. None of
      the volatile compounds previously identified from feathers or uropygial glands
      tested were attractive. Both feather-rubbed cotton balls and hexane extracts of
      feathers were attractive and as attractive as feathers; however, ether extracts
      were not attractive. Feathers clearly contribute to the attraction of host
      seeking Culex spp., and future studies will focus on identification of the
      attractant compounds.

PMID- 16619604
TI  - Population genetics of Ochlerotatus eatoni (Diptera: Culicidae) endemic species
      to two Macaronesian Islands.
AB  - Analyses of 11 isoenzyme loci of Ochlerotatus eatoni (Edwards, 1916), endemic to
      two Macaronesian Islands (Madeira and Tenerife, Canary Islands), revealed
      substantial genetic structure in the study populations. Samples from sites on the
      south and north of Madeira displayed a significant reduction of variability
      compared with those from central Madeira and Tenerife. The Tenerife population
      exhibited a severe deficit of heterozygosity with similar magnitude across all
      the loci examined. The complex pattern of variation in Oc. eatoni is because of
      interplay of breeding structure, genetic drift, and geographical and historical
      factors. From these findings, we concluded that island colonization by Oc. eatoni
      was not marked by founder effect.

PMID- 16619605
TI  - Heated oligonucleotide ligation assay (HOLA): an affordable single nucleotide
      polymorphism assay.
AB  - Most single nucleotide polymorphism (SNP) detection requires expensive equipment
      and reagents. The oligonucleotide ligation assay (OLA) is an inexpensive SNP
      assay that detects ligation between a biotinylated "allele-specific detector" and
      a 3' fluorescein-labeled "reporter" oligonucleotide. No ligation occurs unless
      the 3' detector nucleotide is complementary to the SNP nucleotide. The original
      OLA used chemical denaturation and neutralization. Heated OLA (HOLA) instead uses
      a thermal stable ligase and cycles of denaturing and hybridization for ligation
      and SNP detection. The cost per genotype is approximately US$1.25 with two-allele
      SNPs or approximately US$1.75 with three-allele SNPs. We illustrate the
      development of HOLA for SNP detection in the Early Trypsin and Abundant Trypsin
      loci in the mosquito Aedes aegypti (L.) and at the a-glycerophosphate
      dehydrogenase locus in the mosquito Anopheles gambiae s.s.

PMID- 16619606
TI  - Use of enzyme-linked immunosorbent assay for detection of natural leishmania
      infections in phlebotomine sand flies from southeastern Turkey.
AB  - In total, 320 phelebotomine sand flies from Alibozlu (Osmaniye), Kizyusuflu
      (Osmaniye), and Sanliurfa in southeastern Turkey were tested for the detection
      and identification of Leishmania in vector sand flies by enzyme-linked
      immunosorbent assay with species-specific monoclonal antibodies. We used
      monoclonal antibodies that recognize both Leishmania tropica and Leishmania
      major, and a monoclonal antibody specific only to L. tropica. Phosphate-buffered
      saline and monoclonal antibody M2 recognizing Leishmania amazonensis were used as
      controls. Infection rates of sand flies were 0.9% in Alibozlu, 0% Kizyusuflu, and
      3.6% in Sanliurfa. Positive sand flies were identified as Phlebotomus sergenti
      Parrot and Phlebotomus major syriacus Adler & Theodor.

PMID- 16619607
TI  - Occurrence of serotonin immunoreactivity in the central nervous system and midgut
      of adult female Tabanus nigrovittatus (Diptera: Tabanidae).
AB  - Serotonin is an important neuromessenger used in a variety of signaling pathways
      throughout the animal kingdom. In insects, serotonin has been demonstrated to
      mediate feeding and feeding-related behaviors. In this study, serotonin antibody
      was localized in cells and processes throughout the central nervous system (CNS)
      and midgut of female horse fly Tabanus nigrovittatus Macquart. In the CNS,
      immunoreactivity was localized in cells and processes throughout the brain and
      ventral nerve cord. In the midgut, a fine network of immunoreactive processes was
      observed running along the outer surface of the midgut, with a decrease in
      innervation toward the posterior region of the midgut.

PMID- 16619608
TI  - Larvicidal activity of extracts of Ginkgo biloba exocarp for three different
      strains of Culex pipiens pallens.
AB  - Ethanolic extracts from the Ginkgo biloba L. exocarp from the Chinese ginkgo were
      assayed against larvae of three strains of Culex pipiens pallens Coquillett. The
      chemical compositions were detected using a Hewlett-Packard 6890/5973 mass
      spectrometric detector. The larvicidal bioassay was carried out according to the
      recommendations of the World Health Organization. The analysis of the essential
      oil of ginkgo exocarp showed that its major components are ginkgo acid (85.3%)
      and ginkgo phenolic (5.69%). The larvicidal bioassay showed that extracts of
      ginkgo exocarp have LC50 of 18.6, 12.7, and 25.0 mg/liter for deltamethrin
      susceptible, deltamethrin-resistant, and field strains, respectively. The acute
      toxicity concentrations of the ginkgo extracts that killed 50% (LD50) of Wistar
      rats within 2 wk and young carp within 96 h were 4947.2 mg/kg and 557.9 mg/liter,
      respectively. These results are promising in creating new, effective, and
      affordable approaches to mosquito control.

PMID- 16619609
TI  - Effects of azadirachtin on the development and mortality of Lutzomyia longipalpis
      larvae (Diptera: Psychodidae: Phlebotominae).
AB  - The effects of azadirachtin A added to the standard diet on the development,
      mortality, and metamorphosis of Lutzomyia longipalpis Lutz & Neiva, 1912 were
      studied. Concentrations of 0.1, 1.0, and 10.0 microg of azadirachtin/mg of diet
      significantly increased larval mortality in comparison with nontreated insects.
      Concentrations 0.1 and 1.0 microg blocked the molt of larvae, which remained as
      third instars until the end of the experiment. The 10 microg/mg concentration
      resulted in greater molt inhibition. In this group, all insects stopped their
      development as second instars. Simultaneous addition of ecdysone (1 microg/mg) to
      the standard diet containing azadirachtin counteracted the effects of
      azadirachtin on mortality and inhibition of ecdysis. These results indicate that
      azadirachtin is a potent growth inhibitor of L. longipalpis.

PMID- 16619610
TI  - Insecticide resistance in Anopheles funestus (Diptera: Culicidae) from
      Mozambique.
AB  - Malaria control in southern Mozambique is currently by indoor residual carbamate
      insecticide treatment, with pyrethroid-treated bed-nets distributed to pregnant
      women and children under five in northern Mozambique. The susceptibility of
      Anopheles funestus s.s. to pyrethroid, carbamate, organochlorine, and
      organophosphorus insecticides was determined by World Health Organization adult
      mosquito susceptibility tests at 19 localities in Mozambique, from March 2000 to
      July 2002. Biochemical assays were carried out on mosquitoes from the same
      families to detect shifts in the quantity or activity of enzyme families involved
      in insecticide detoxification. An. funestus from all localities remained fully
      susceptible to DDT and the organophosphorus insecticide malathion. A high level
      of pyrethroid resistance was detected in An. funestus populations in southern
      Mozambique. An. funestus outside Maputo province were still susceptible to
      pyrethroids. An. funestus from six localities also were resistant to carbamate
      insecticides propoxur and bendiocarb. Both pyrethroid and carbamate resistance
      occurred in five of these six localities. Mosquitoes from five of the localities
      with elevated p450 estimates, compared with the insecticide-susceptible Durban
      strain, were pyrethroid-resistant. The only exception to this trend was Mozal,
      which had elevated p450 estimates but full pyrethroid susceptibility by bioassay.
      The lack of cross-resistance between pyrethroids and DDT in Mozambican An.
      funestus suggests that a kdr-type target site resistance mechanism has not been
      selected. Low levels of insecticide-insensitive acetylcholinesterase, the target
      site for carbamates and organophosphates, were found in all populations tested.
      The high level of metabolically based pyrethroid resistance has implications for
      current malaria control programs in Mozambique.

PMID- 16619611
TI  - Insecticide resistance in Anopheles arabiensis and Anopheles gambiae from
      Mozambique.
AB  - Malaria control in the southern part of Mozambique is currently by indoor
      residual spraying with a carbamate insecticide and by pyrethroid-treated bed-nets
      distributed to pregnant women and children under five in northern Mozambique. The
      susceptibility of Anopheles gambiae s.s. and Anopheles arabiensis Patton to
      pyrethroid, carbamate, organochlorine, and organophosphorus insecticides was
      determined by World Health Organization adult mosquito susceptibility tests at 17
      localities in Mozambique, from March 2000 to July 2002. Biochemical assays were
      carried out on mosquitoes from the same families to detect shifts in the quantity
      or activity of enzyme families involved in insecticide detoxification. An.
      gambiae s.s. from all localities remained fully susceptible to DDT and the
      organophosphorus insecticide malathion. A low level of pyrethroid resistance was
      detected in populations in southern Mozambique. Populations outside Maputo
      province were still susceptible to pyrethroids. Low level resistance to the
      carbamate propoxur also was detected in An. arabiensis from two localities.
      Mosquitoes from five of the localities had elevated p450 estimates, compared with
      the insecticide susceptible Durban strain. The lack of cross-resistance between
      pyrethroids and DDT in Mozambican populations suggests that a kdr-type target
      site resistance mechanism has not been selected. Increased frequencies of
      insecticide insensitive acetylcholinesterase, the target site for carbamates and
      organophosphates, were found in 16 of the populations tested. Although vector
      control with bendiocarb is not being compromised by the presence of the
      acetylcholinesterase mechanism alone, the high level of insensitive
      acetylcholinesterase unless sensibly managed may have long-term implications for
      malaria control programs in Mozambique.

PMID- 16619612
TI  - Evidence that scabies mites (Acari: Sarcoptidae) influence production of
      interleukin-10 and the function of T-regulatory cells (Tr1) in humans.
AB  - We performed experiments to determine whether an extract of Sarcoptes scabiei (De
      Geer) influenced cytokine expression by human T-lymphocytes. Peripheral blood
      mononuclear cells from five sensitized donors and four donors without
      sensitization to scabies mites were challenged with a T-cell mitogen alone, with
      scabies extract (SS) alone, or with mitogen and SS together. Supernatants were
      analyzed for the cytokines interferon-gamma (IFNgamma), interleukin (IL)-2, IL-4,
      and IL-10. No IL-2 or IL-4 was produced in response to scabies extract. Cells
      from both naive and sensitized donors produced large amounts of IFNgamma and IL
      10. The lack of IL-4 but high levels of IL-10 suggests that IL-10 was likely
      secreted by type 1 T-regulatory cells, which were activated by something in the
      scabies extract. IL-10 has anti-inflammatory and immune-suppressive effects. It
      may play a key role in depressing the inflammatory and immune responses in humans
      so that clinical symptoms are not seen until 4-6 wk after a person becomes
      infested with scabies mites.

PMID- 16619613
TI  - Horizontal transfer of Shiga toxin and antibiotic resistance genes among
      Escherichia coli strains in house fly (Diptera: Muscidae) gut.
AB  - Whether the house fly, Musca domestica L., gut is a permissive environment for
      horizontal transfer of antibiotic resistance and virulence genes between strains
      of Escherichia coli is not known. House flies were immobilized and force fed
      suspensions of defined, donor strains of E. coli containing chloramphenicol
      resistance genes on a plasmid, or lysogenic, bacteriophage-born Shiga toxin gene
      stx1 (bacteriophage H-19B::Ap1). Recipient strains were E. coli lacking these
      mobile elements and genes but having rifampicin as a selectable marker. Plasmid
      transfer occurred at rates of 10(-2) per donor cell in the fly midgut and 10(-3)
      in the fly crop after 1 h of incubation postfeeding. Bacteriophage transfer rate
      was approximately 10(-6) per donor cell without induction, but induction with
      mitomycin C increased rates of transfer to 10(-2) per donor cell. These findings
      show that genes encoding antibiotic resistance or toxins will transfer
      horizontally among bacteria in the house fly gut via plasmid transfer or phage
      transduction. The house fly gut may provide a favorable environment for the
      evolution and emergence of pathogenic bacterial strains through acquisition of
      antibiotic resistance genes or virulence factors.

PMID- 16619614
TI  - Laboratory transmission of Japanese encephalitis and West Nile viruses by
      molestus form of Culex pipiens (Diptera: Culicidae) collected in Uzbekistan in
      2004.
AB  - We evaluated the molestus form of Culex pipiens pipiens (L.) (hereafter referred
      to as "molestus") captured near Tashkent, Uzbekistan, for their ability to
      transmit Japanese encephalitis (family Flaviviridae, genus Flavivirus, JEV) and
      West Nile (family Flaviviridae, genus Flavivirus, WNV) viruses under laboratory
      conditions. These molestus were highly competent laboratory vectors of WNV, with
      infection and dissemination rates of 96 and 81%, respectively. Approximately 75%
      of female molestus that fed after development of a disseminated infection
      transmitted virus by bite. Therefore, approximately 60% of those molestus taking
      a second bloodmeal between 16 and 25 d after an infectious bloodmeal would be
      expected to transmit WNV by bite. In contrast, these molestus were less efficient
      vectors of JEV, with infection and dissemination rates of 51 and 25%,
      respectively. In addition, only 33% of individuals with a disseminated infection
      transmitted JEV by bite, indicating a significant salivary gland barrier.
      Therefore, only approximately 8% of orally exposed individuals would be expected
      to transmit JEV by bite if they took a second bloodmeal 16-25 d later. These data
      indicate that the molestus form of Cx. p. pipiens should be considered a
      potentially important vector of WNV in Uzbekistan and may become involved in the
      transmission of JEV, should this virus be introduced into Uzbekistan.

PMID- 16619615
TI  - Glossina proteolytic lectin does not require a carbohydrate moiety for enzymatic
      or trypanosome-transforming activities.
AB  - The developmental cycle of the cyclically transmitted African trypanosome
      involves an obligatory passage through the tsetse fly, Glossina spp. This
      intricate relationship requires the presence of molecules within the insect
      vector, including a midgut lectin, that interact with the trypanosome. Recently,
      a gene encoding for a proteolytic lectin, with trypanosome-transforming activity,
      was isolated from a midgut cDNA library of Glossina fuscipes fuscipes Austen in
      our laboratory. Using the same approach, we have identified a similar gene from a
      midgut cDNA library of Glossina austeni (Newstead). The protein encoded by this
      gene was expressed in bacteria and a baculovirus-based expression system. The
      baculovirus-expressed lectin was found in the medium of baculovirus-infected Sf
      21 cell cultures, indicating that the tsetse fly-derived signal peptide was
      recognized and cleaved by the Sf-21 cells. The baculovirus-expressed protein also
      was glycosylated despite the absence of classical O-linked and N-linked sugar
      attachment motifs. Both the baculovirus- and bacterium-expressed lectin proteins
      were shown to agglutinate trypanosomes and rabbit red blood cells in vitro. This
      agglutination was strongly inhibited by D-glucosamine. D-Glucosamine also
      inhibited the action of the authentic and recombinant lectins upon the
      chromogenic substrate Chromozym TRY. Interestingly, both baculovirus- and
      bacterium-expressed lectins showed no significant differences in terms of these
      activities, indicating that a sugar moiety is not essential for biological
      activity. Our results provide an important molecular tool for further
      characterization of Glossina proteolytic lectin.

PMID- 16619616
TI  - Effects of temperature on the transmission of west nile virus by Culex tarsalis
      (Diptera: Culicidae).
AB  - Culex tarsalis Coquillett females were infected with the NY99 strain of West Nile
      virus (family Flaviviridae, genus Flavivirus, WNV) and then incubated under
      constant temperatures of 10-30 degrees C. At selected time intervals,
      transmission was attempted using an in vitro capillary tube assay. The median
      time from imbibing an infectious bloodmeal until infected females transmitted WNV
      (median extrinsic incubation period, EIP50) was estimated by probit analysis. By
      regressing the EIP rate (inverse of EIP50) as a function of temperature from 14
      to 30 degrees C, the EIP was estimated to require 109 degree-days (DD) and the
      point of zero virus development (x-intercept) was estimated to be 14.3 degrees C.
      The resulting degree-day model showed that the NY99 WNV strain responded to
      temperature differently than a lineage II strain of WNV from South Africa and
      approximated our previous estimates for St. Louis encephalitis virus (family
      Flaviviridae, genus Flavivirus, SLEV). The invading NY99 WNV strain therefore
      required warm temperatures for efficient transmission. The time for completion of
      the EIP was estimated monthly from temperatures recorded at Coachella Valley, Los
      Angeles, and Kern County, California, during the 2004 epidemic year and related
      to the duration of the Cx. tarsalis gonotrophic cycle and measures of WNV
      activity. Enzootic WNV activity commenced after temperatures increased, the
      duration of the EIP decreased, and virus potentially was transmitted in two or
      less gonotrophic cycles. Temperatures in the United States during the epidemic
      summers of 2002-2004 indicated that WNV dispersal and resulting epicenters were
      linked closely to above-average summer temperatures.

PMID- 16619617
TI  - Plasmodium development in white-eye (kh(w)) and transformed strains (kh43) of
      Aedes aegypti (Diptera: Culicidae).
AB  - Xanthurenic acid (XA) has been implicated as an inducer in vivo of exflagellation
      in Plasmodium spp. Consequently, the development of Plasmodium gallinaceum was
      assessed in a white-eye mosquito strain, kh(w), of Aedes aegypti (L.), which is
      deficient in XA because of a mutation of the gene encoding the enzyme kynurenine
      hydroxylase, and in a transformed line of kh(w) mosquitoes that carry the wild
      type cn+ gene of Drosophila melanogaster Meigen and express a functional enzyme
      necessary for XA production. Although XA was not detectable in kh(w) mosquitoes
      by using high-pressure liquid chromatography with electrochemical detection,
      parasites were able to develop. Transformed kh(w) mosquitoes failed to
      consistently support parasite development at higher prevalences and mean
      intensities than did the nontransformed kh(w) lines, even though XA was
      detectable. These data suggest that factors other than XA may play a role in
      initiating Plasmodium development in vivo.

PMID- 16619618
TI  - Transmission of vesicular stomatitis New Jersey virus to cattle by the biting
      midge Culicoides sonorensis (Diptera: Ceratopogonidae).
AB  - Laboratory-reared Culicoides sonorensis Wirth & Jones were infected with
      vesicular stomatitis virus serotype New Jersey (family Rhabdoviridae, genus
      Vesiculovirus, VSNJV) through intrathoracic inoculation. After 10-d incubation at
      25 degrees C, these insects were allowed to blood feed on four steers. Two other
      steers were exposed to VSNJV through intralingual inoculation with 10(8) tissue
      culture infective dose50 VSNJV. All six steers became seropositive for VSNJV. The
      results demonstrate the ability of C. sonorensis to transmit VSNJV to livestock.
      Only the animals intralingually inoculated with VSNJV showed clinical signs in
      the form of vesicles at the site of inoculation. Uninfected C. sonorensis allowed
      to feed on the exposed animals did not become infected with VSNJV. Animals
      infected by C. sonorensis showed a slower antibody response compared with
      intralingually inoculated animals. This is probably because of different amounts
      of virus received via insect transmission and syringe inoculation. A significant
      difference was found in the serum acute-phase protein alpha-1-acid glycoprotein
      in animals that received VSNJV through C. sonorensis transmission. These animals
      had previously been exposed to insect attack in the field compared with
      intralingually inoculated animals and C. sonorensis-infected animals that had
      been protected from insect attack. The failure to observe clinical signs of
      vesicular stomatitis through transmission of VSNJV by C. sonorensis may explain
      widespread subclinical infections during vesicular stomatitis epidemics.

PMID- 16619619
TI  - Importance of socioeconomic status and tree holes in distribution of Aedes
      mosquitoes (Diptera: Culicidae) in Jodhpur, Rajasthan, India.
AB  - Immature Aedes mosquitoes were found in domestic, peridomestic, and tree hole
      habitats within three socioeconomic strata of Jodhpur, a city within an arid area
      of Rajasthan, India, endemic for dengue. Peridomestic habitats served as a
      persistent source of Aedes vectors, especially those used for watering cows for
      religious reasons that were located within high socioeconomic areas. Domestic
      (indoor) containers within low socioeconomic strata showed a higher container
      index (27.0%) than periurban areas with cattle sheds (14.3%) or high
      socioeconomic areas (18.1%). Mosquitoes were collected in tree holes at zoos and
      gardens supporting several species of monkeys. Six of 67 Aedes albopictus Skuse
      reared from immatures collected in tree holes tested positive for dengue antigen
      acquired through vertical transmission, possibly indicating a persistence
      mechanism for dengue virus within an urban environment.

PMID- 16619620
TI  - Evaluating satellite sensor-derived indices for Lyme disease risk prediction.
AB  - The wetness and greenness indices created using Landsat Thematic Mapper (TM) data
      from June 1995 and 1997 and July 2002 were tested for their ability to predict
      the location of sites with different levels of nymphal blacklegged tick, Ixodes
      scapularis Say, abundance in Rhode Island. In 1995, there were statistically
      significant differences in the mean of greenness and wetness indices between
      sites classified as low and moderate tick abundance areas (P = 0.005 and P =
      0.041, respectively). In 1997, there also were statistically significant
      differences in the mean of the greenness and wetness indices, but these
      differences were between the grouping of low/moderate tick abundance and the high
      tick abundance category (P = 0.023 and P = 0.015, respectively). The same indices
      from the 2002 image were not significant predictors of tick abundance. It may be
      that Landsat TM-derived indices can be used to predict nymphal blacklegged tick
      abundance in years (e.g., 1995 and 1997) when tick abundance is lower than
      average but not in years when it is higher (e.g., 2002). Thus, it seems unlikely
      that these remotely sensed indices will be very useful for modeling
      nonperidomestic Lyme disease risk over a large region in Rhode Island.

PMID- 16619621
TI  - Overwintering of West Nile virus in Southern California.
AB  - West Nile virus (family Flaviviridae, genus Flavivirus, WNV) invaded southern
      California during 2003, successfully overwintered, amplified to epidemic levels,
      and then dispersed to every county in the state. Although surveillance programs
      successfully tracked and measured these events, mechanisms that allowed the
      efficient overwintering and subsequent amplification of WNV have not been
      elucidated. Our current research provided evidence for three mechanisms whereby
      WNV may have persisted in southern California during the winters of 2003-2004 and
      2004-2005: 1) continued enzootic transmission, 2) vertical transmission by Culex
      mosquitoes, and 3) chronic infection in birds. WNV was detected in 140 dead birds
      comprising 32 species, including 60 dead American crows, thereby verifying
      transmission during the November-March winter period. Dead American crows provide
      evidence of recent transmission because this species always succumbs rapidly
      after infection. However, WNV RNA was not detected concurrently in 43,043
      reproductively active female mosquitoes comprising 11 species and tested in 1,258
      pools or antibody in sera from 190 sentinel chickens maintained in 19 flocks.
      Although efficient vertical transmission by WNV was demonstrated experimentally
      for Culex tarsalis Coquillett infected per os, 369 females collected diapausing
      in Kern County and tested in 32 pools were negative for WNV. Vertical
      transmission was detected in Culex pipiens quinquefasciatus Say adults reared
      from field-collected immatures collected from Kern County and Los Angeles during
      the summer transmission period. Chronic infection was detected by finding WNV RNA
      in 34 of 82 birds that were inoculated with WNV experimentally, held for >6 wk
      after infection, and then necropsied. Frequent detection of WNV RNA in kidney
      tissue in experimentally infected birds >6 wk postinfection may explain, in part,
      the repeated detection of WNV RNA in dead birds recovered during winter,
      especially in species such as mourning doves that typically do not die after
      experimental infection. In summary, our study provides limited evidence to
      support multiple modes of WNV persistence i n southern California. Continued
      transmission andvertical transmission by Culex p. quinquefasciatus Say seem
      likely candidates for further study.

PMID- 16619622
TI  - Role of corvids in epidemiology of west Nile virus in southern California.
AB  - The invasion of different southern California landscapes by West Nile virus (WNV)
      and its subsequent amplification to epidemic levels during 2004 enabled us to
      study the impact of differing corvid populations in three biomes: the hot
      Colorado desert with few corvids (Coachella Valley), the southern San Joaquin
      Valley (Kern County) with large western scrub-jay but small American crow
      populations, and the cool maritime coast (Los Angeles) with a large clustered
      American crow population. Similar surveillance programs in all three areas
      monitored infection rates in mosquitoes, seroconversion rates in sentinel
      chickens, seroprevalence in wild birds, numbers of dead birds reported by the
      public, and the occurrence of human cases. Infection rates in Culex tarsalis
      Coquillett and sentinel chicken seroconversion rates were statistically similar
      among all three areas, indicating that highly competent mosquito hosts were
      capable of maintaining enzootic WNV transmission among less competent and widely
      distributed avian hosts, most likely house sparrows and house finches. In
      contrast, infection rates in Culex pipiens quinquefasciatus Say were
      statistically higher in Kern and Los Angeles counties with elevated corvid
      populations than in Coachella Valley with few corvids. Spatial analyses of dead
      corvids showed significant clusters near known American crow roosts in Los
      Angeles that were congruent with clusters of human cases. In this area, the
      incidence of human and Cx. p. quinquefasciatus infection was significantly
      greater within corvid clusters than without, indicating their importance in virus
      amplification and as a risk factor for human infection. In contrast the uniform
      dispersion by territorial western scrub-jays resulted in a high, but evenly
      distributed, incidence of human disease in Kern County.

PMID- 16619623
TI  - An avian contribution to the presence of Ixodes pacificus (Acari: Ixodidae) and
      Borrelia burgdorferi on the Sutter Buttes of California.
AB  - Birds from 45 species were sampled during three spring seasons from an isolated
      canyon on the Sutter Buttes in California for the presence of subadult stages of
      Ixodes pacificus Cooley & Kohls, and for infection with Borrelia burgdorferi
      Johnson, Schmid, Hyde, Steigerwalt & Brenner. These birds were found to have an
      infestation prevalence of 45%, a density of 1.7 ticks per bird, and an intensity
      of 3.8 ticks per infested bird. There was a significant difference in the I.
      pacificus infestations between canopy and ground-dwelling birds. Birds also
      demonstrated an overall infection with B. burgdorferi of 6.4% with significant
      difference between bird species. Amplification and subsequent sequencing of the
      23s-5s rRNA intergenic spacer region of the Borrelia genome from one bird, a
      hermit thrush, Catharus guttatus (Nuttall), showed that the infection in this
      bird was caused by B. burgdorferi sensu stricto; the first such finding in a bird
      from the far west. Our results suggest that birds play a role in the distribution
      and maintenance of I. pacificus, and possibly of B. burgdoferi, at the Sutter
      Buttes, CA.

PMID- 16619624
TI  - Mosquito species (Diptera: Culicidae) and the transmission of Ross River virus in
      Brisbane, Australia.
AB  - This study aimed to identify the major mosquito vectors of Ross River virus
      (family Togaviridae, genus Alphavirus, RRV) and to explore the threshold of
      mosquito abundance necessary for RRV transmission in Brisbane, Australia. Data on
      the monthly counts of RRV cases by statistical local areas from the Queensland
      Health and the monthly mosquito abundance in Brisbane between November 1998 and
      December 2001 from the Brisbane City Council were used to assess the pairwise
      relationship between mosquito abundance and the incidence of RRV disease over a
      range of time lags using cross-correlations. We used time series Poisson
      regression models to identify major mosquito species associated with incidence of
      RRV after adjusting for overdispersion, maximum temperature, autocorrelation, and
      seasonality. Our results show that Aedes vigilax (Skuse) (relative risk [RR] =
      1.32; 95% CI = 1.01-1.74 per 100 mosquitoes per trap) and Culex annulirostris
      (Skuse) (RR = 1.14, 95% CI = 1.04-1.24 per 100 mosquitoes per trap) were most
      strongly associated with RRV transmission at a lag of 1 mo. Classification and
      regression tree (CART) analyses indicate that the occurrence of RRV was
      associated with an average monthly mosquito abundance ofAedes vigilax above 72
      and Cx. annulirostris above 52. The validation analyses indicate that the crude
      agreement between predicted values and actual observations was 76% (sensitivity,
      61%; specificity, 80%). The results may have applications as a decision support
      tool in planning disease control and risk-management programs.

PMID- 16619625
TI  - Use of remote sensing and geographic information systems to predict locations of
      Anopheles darlingi-positive breeding sites within the Sibun River in Belize,
      Central America.
AB  - Previous studies have identified several anopheline species integral to the
      transmission of malaria in Belize. The highly efficient vector, Anopheles
      darlingi Root, is currently considered the most important. The preferred larval
      habitat of An. darlingi has been described as floating detritus patches, which
      are commonly associated with overhanging spiny bamboo, Guadua longifolia (E.
      Fourn.), along river margins. The objectives of this study were to use remote
      sensing and geographic information system (GIS) tools to 1) define the landscape
      features (i.e., river curvature, land cover, and house locations) associated with
      An. darlingi-positive breeding habitats and 2) determine the association between
      cleared land cover and the growth of spiny bamboo. A systematic survey was
      conducted in which all detritus patches of at least 1 m2 were sampled, mapped
      using GPS, and characterized by cause of habitat lodging. Bamboo stretches
      growing along the river margins also were mapped. Spatial analyses of satellite
      imagery found no associations between river characteristics or land cover with
      positive An. darlingi habitats. In addition, there was no significant difference
      in cleared versus forested land cover in relation to the presence or absence of
      bamboo. Results indicate that the average distance from homes to negative
      habitats was significantly greater than from positive detritus mats. Based on the
      land cover and river characteristics used, our results do not support the use of
      remote sensing as a predictive tool to locate specific areas within rivers
      positive for An. darlingi habitats.

PMID- 16619626
TI  - Characterizing population dynamics of Aedes sollicitans (Diptera: Culicidae)
      using meteorological data.
AB  - Numerous studies have investigated the role of weather on insect species. For
      mosquitoes, these studies have yielded mixed results. Although it is clear that
      weather impacts mosquito population dynamics, these investigations have failed to
      accurately characterize their fluctuations. We use a novel graphical method to
      examine large numbers of meteorological aggregations of varying lengths and lags
      simultaneously to establish relationships between these summary variables and
      mosquito counts, to gain a better understanding of the weather effects. Poisson
      regression models were developed to characterize the population dynamics of Aedes
      sollicitans (Walker) by using meteorological data and a 34-yr set of daily
      mosquito count data. The models accurately characterize mosquito dynamics over
      time and space. The aggregated meteorological variables included in the model
      were lowest minimum tides between days 27 and 14 before trapping, total
      precipitation between days 22 and 9, total precipitation on day 1 and the day of
      trapping, cooling degree-days on day 0, average minimum relative humidity between
      days 28 and 9, lowest stream flow from day 11 to day 0, and lowest minimum
      temperature between days 28 and 13.

PMID- 16619627
TI  - Investigation of ground level and remote-sensed data for habitat classification
      and prediction of survival of Ixodes scapularis in habitats of southeastern
      Canada.
AB  - In southeastern Canada, most populations of Ixodes scapularis Say, the Lyme
      disease vector, occur in Carolinian forests. Climate change projections suggest a
      northward range expansion of I. scapularis this century, but it is unclear
      whether more northerly habitats are suitable for I. scapularis survival. In this
      study, we assessed the suitability of woodlands of the Lower Great Lakes/St.
      Lawrence Plain region for I. scapularis by comparing tick egg survival in four
      different woodlands. Woodlands where I. scapularis are established, and sand dune
      where I. scapularis do not survive, served as positive and negative control
      sites, respectively. At two woodland sites, egg survival was the same as at the
      positive control site, but at two of the sites survival was significantly less
      than either the positive control site, or one of the other test sites. Egg
      survival in all woodland sites was significantly higher than in the sand dune
      site. Ground level habitat classification discriminated among woodlands in which
      tick survival differed. The likelihood that I. scapularis populations could
      persist in the different habitats, as deduced using a population model of I.
      scapularis, was significantly associated with variations in Landsat 7 ETM+ data
      (normalized difference vegetation index [NDVI] and Tasselled Cap indices). The
      NDVI index predicted habitat suitability at Long Point, Ontario, with high
      sensitivity but moderate specificity. Our study suggests that I. scapularis
      populations could establish in more northerly woodland types than those in which
      they currently exist. Suitable habitats may be detected by ground-level habitat
      classification, and remote-sensed data may assist this process.

PMID- 16619628
TI  - Geographical distribution patterns and habitat suitability models for presence of
      host-seeking ixodid ticks in dense woodlands of Mendocino County, California.
AB  - We used drag sampling to examine the geographical distribution patterns of ixodid
      ticks engaging in open (non-nidicolous) host-seeking behavior in dense woodland
      habitats of the climatically and ecologically diverse Mendocino County in north
      coastal California. The findings based on this sampling methodology reflect risk
      of human exposure to host-seeking ticks rather than the true distribution of the
      ticks. Drag sampling in 78 sites yielded 7,860 nymphal or adult Ixodes pacificus
      Cooley & Kohls, 220 Dermacentor occidentalis Marx, 150 Ixodes spinipalpis Hadwen
      & Nuttall, 15 Hemaphysalis leporispalustris (Packard), 12 Ixodes angustus
      Neumann, 12 Ixodes auritulus Neumann, and a single Dermacentor variabilis (Say).
      I. pacificus, which is the primary vector of the Lyme disease spirochete Borrelia
      burgdorferi to humans in California, occurred in all 78 sites examined. D.
      occidentalis, another tick species commonly biting humans in California, and H.
      leporispalustris typically were encountered in oak-associated woodlands in the
      central or eastern parts of the county. In contrast, three species of Ixodes
      ticks (I. angustus, I. auritulus, and I. spinipalpis) most commonly were found
      questing openly in woodlands with redwood present in the western part of the
      county. I. angustus and I. spinipalpis are occasional human biters and known
      experimental vectors of B. burgdorferi. Our study represents the first collection
      of large numbers of openly host-seeking I. spinipalpis ticks. Univariate tests of
      associations between presence of ticks (D. occidentalis, H. leporispalustris, I.
      angustus, I. auritulus, or I. spinipalpis) and environmental geographical
      information systems-remote sensing (GIS/ RS)-based data indicated that elevation,
      number of growing degree-days, and tasseled cap brightness, greenness, and
      wetness are especially useful predictors of presence of openly hostseeking ticks.
      Combinations of the above-mentioned GIS/RS-based data yielded significant
      logistic regression models for habitat suitability of host-seeking ticks for all
      five above-mentioned species. The model equations were used to create spatial
      surfaces of predicted presence of suitable habitat for openly host-seeking ticks
      in Mendocino County dense woodlands.

PMID- 16619629
TI  - Impact of sustained use of insecticide-treated bednets on malaria vector species
      distribution and culicine mosquitoes.
AB  - Insecticide-treated bednets (ITNs) significantly reduce malaria vector
      populations. Susceptibility to ITNs differs by vector species, and culicine
      mosquitoes have not been shown to be significantly affected by the use of ITNs.
      We examined the impact of 2-4 yr of ITN use on malaria vector species
      distribution and culicine mosquitoes. Routine entomological surveillance was
      conducted in adjacent areas with and without ITNs from November 1999 to January
      2002. Use of ITNs reduced the proportion of Anopheles gambiae Giles relative to
      Anopheles arabiensis Giles. The number of culicines per house was significantly
      lower in the ITN area than in the neighboring area. Changes in the An. gambiae
      sibling species distribution may help to explain apparent mosquito behavioral
      changes attributed to ITNs. Reductions in culicines by ITNs may have implications
      for community perceptions of ITN effectiveness and for control of other diseases
      such as lymphatic filariasis.

PMID- 16619630
TI  - Effects of prior infestation on host choice of bat flies (Diptera: Streblidae).
AB  - Experimental approaches provide insight into the dynamics of species competition
      and coexistence, but studies of ectoparasitic arthropods are rare. Host choice
      experiments were undertaken in Amazonian Peru, by using obligate bat fly
      parasites of Seba's short-tailed bat, Carollia perspicillata (L.). The fly
      species Trichobius joblingi Wenzel strongly preferred clean hosts to those
      previously infested with individuals of T. joblingi. Abundance thresholds may
      limit conspecific parasites on host individuals, and similar morphologies and
      habitat use may increase intraspecific competition among individuals of T.
      joblingi. T. joblingi did not distinguish between clean hosts and those
      previously infested with flies of another species, Speiseria ambigua Kessel.
      Results suggest that the presence of a morphologically dissimilar species does
      not preclude subsequent colonization. Differential microhabitat selection, aided
      by adaptive morphology, may facilitate species coexistence among ectoparasitic
      bat fly species.

PMID- 16619631
TI  - Detection of Anaplasma phagocytophilum and Babesia odocoilei DNA in Ixodes
      scapularis (Acari: Ixodidae) collected in Indiana.
AB  - The blacklegged tick, Ixodes scapularis Say, first reported in Indiana in 1987,
      has now been detected in more than half of Indiana's counties. The first case of
      human granulocytic ehrlichiosis (human anaplasmosis) in Indiana was reported in
      2002. We now report the detection of Anaplasma phagocytophilum and Babesia
      odocoilei (Emerson and Wright 1968) in I. scapularis ticks collected in northern
      Indiana. Using polymerase chain reaction analysis, 41 of 193 adult ticks (21.2%)
      collected from deer were positive for A. phagocytophylum, and 22 (11.4%) were
      positive for Babesia sp. Restriction fragment analysis of 12, and sequencing of
      another five of the amplified products identified these parasites as B.
      odocoilei. Five ticks (2.6%) were coinfected. Eight of 68 questing adult ticks
      (11.8%) were positive for A. phagocytophilum; seven (10.3%) were positive for
      Babesia sp. Six of the latter seven positive samples were determined to be B.
      odocoilei by restriction fragment analysis and sequencing of two samples. None of
      39 pools of nymphs was positive for Babesia sp. Three of 15 ticks (20%) collected
      from a dog were positive for A. phagocytophilum and three ticks (20%) were
      positive for Babesia sp. One was confirmed as B. odocoilei. One tick was
      coinfected. This is the first report of the presence of these two agents in ticks
      in Indiana.

PMID- 16619632
TI  - Women in neurological surgery. Matson Memorial Lecture.

PMID- 16619633
TI  - Best-practice surgical techniques for intrathecal baclofen therapy.
AB  - In March 2004, a multidisciplinary conference, "ITB Therapy Best Practice Forum,"
      was held in Minneapolis, Minnesota. The goal of the conference was to develop
      recommendations for techniques to implant intrathecal baclofen (ITB) pump and
      catheter systems more effectively and with fewer complications. The authors
      present the techniques for optimal pump and catheter implantation, including
      subfascial pump placement; insertion of the Tuohy needle in an oblique,
      paramedian trajectory; and positioning of the catheter tip at levels commensurate
      with the therapeutic indication: approximately T10-12 for spastic diplegia, C5-T2
      for spastic tetraparesis, and C1-4 for generalized secondary dystonia. Techniques
      to minimize the incidence of cerebrospinal fluid leakage are described, including
      the identification of preoperative occult hydrocephalus and the use of a suture
      ligature around the Tuohy needle at its exit site from the fascia. Techniques to
      minimize surgery-related infection are also detailed; most involve the use of
      iodine solutions multiple times intraoperatively. Techniques to insert
      intrathecal catheters during spinal fusion are addressed, particularly the
      technique of inserting the catheter cephalad to the fusion site. Panel members
      advocate the aforementioned techniques to improve the efficacy of and decrease
      the morbidity associated with ITB therapy.

PMID- 16619634
TI  - Severe intracranial hypertension in slit ventricle syndrome managed using a
      cisterna magna-ventricle-peritoneum shunt.
AB  - OBJECT: Severely increased intracranial pressure (ICP) can be life threatening in
      patients who had previously undergone shunt treatment but who do not experience
      ventricular enlargement. The authors analyzed the utility of placing shunts into
      the cisterna magna concurrently with ventricular shunts in patients who were not
      candidates for lumboperitoneal (LP) shunt placement. METHODS: Ten patients
      treated with cisterna magna-ventricle-peritoneum (CMVP) shunts for complex
      problems of shunt function were reviewed retrospectively. All patients had
      documented increases in ICP and ventricles that did not expand despite life
      threatening increases (> 80 mm Hg in one case) in ICP. Between 1995 and 2003, 10
      patients (four males and six females, age range 4-32 years) were identified as
      having life-threatening increases in ICP despite small or slit-like ventricles on
      imaging studies. Each episode was documented with intraparenchymal pressure
      monitoring. All patients had documented ventricular catheter failures at the time
      of the intervention, and all had undergone at least one previous attempt to treat
      the condition with a valve upgrade and replacement of the ventricular catheter.
      Three patients had achondroplasia, four had spina bifida, and three had a
      preexisting Chiari malformation Type I. All patients improved after the
      procedure, and none suffered permanent complications. For at least 48 hours after
      surgery, all patients underwent intraparenchymal monitoring of ICP (an
      intraparenchymal monitor was used that documented normal ICP). CONCLUSIONS: The
      CMVP shunts are an excellent option for patients who are not candidates for LP
      shunts but who have high ICP and ventricles that do not enlarge at shunt failure.
      The ability to access the spinal fluid in the cortical subarachnoid space
      presumably accounts for this success.

PMID- 16619635
TI  - Nonaccidental head trauma as a cause of childhood death.
AB  - OBJECT: The authors present the demographic and clinical information in 36
      children who died as a result of abusive head trauma at a Level 1 pediatric
      trauma center between January 1, 1997, and January 1, 2004. METHODS: Abusive head
      trauma was defined as radiographic evidence of intracranial injury and
      documentation from a multidisciplinary child protection team that the injury was
      nonaccidental. There was no sex bias for the children in the 1st year of life
      (nine girls, nine boys). In children older than 1 year of age, boys were much
      more likely to be victims (14 boys, four girls). At the time of admission, every
      child exhibited a seriously impaired level of consciousness and 81% had retinal
      hemorrhages. Injuries to other organ systems were rare (17%). The most common
      abnormality found on neuroimaging studies was subdural hematoma. Six children
      underwent craniotomy for extraaxial hematomas. Death occurred within 24 hours
      after hospital admission in one half of the cases. CONCLUSIONS: Abusive head
      trauma was the cause of death in 36 (86%) of the 42 children whose deaths were
      classified as nonaccidental at the Children's Hospital in Denver between 1997 and
      2003. The authors were unable to identify anything that could have been done from
      a medical or neurosurgical viewpoint to prevent the deaths of these children
      after they came to medical attention.

PMID- 16619636
TI  - Heavy water inhibiting the expression of transforming growth factor-beta1 and the
      development of kaolin-induced hydrocephalus in mice.
AB  - OBJECT: The authors investigated the effects of heavy water (D2O) on
      intrameningeal fibrosis and on the expression of cytokine production in mice with
      kaolin-induced hydrocephalus. METHODS: Mice in which kaolin was injected into the
      cisterna magna were divided into two groups: 1) Group H, which had free access to
      H2O as tap water; and 2) Group D, which had free access to 30% D2O as tap water
      before and after kaolin injection. A distilled water-injected group, which had
      free access to H2O as tap water was designated the sham-operated group. The
      authors examined the effects of D2O within 28 days after injection on the
      development of hydrocephalus and intrameningeal fibrosis, as well as on the
      expression levels of several inflammatory and fibrogenic cytokines: transforming
      growth factor-beta1 (TGFbeta1), fibroblast growth factor-2 (FGF2), platelet
      derived growth factor (PDGF)-BB, and interleukin (IL)-6. The cerebral ventricles
      were less expanded, and intrameningeal fibrosis was milder in Group D than in
      Group H. The proliferation of fibroblasts was assessed by applying the
      bromodeoxyuridine labeling index, which was lower in Group D than in Group H.
      Expression of TGFbeta1 in the macrophages, choroid plexus, and meninges was
      inhibited in Group D but not in Group H. The serum level of total TGFbeta1 was
      significantly lower in Group D than in Group H on Day 14, whereas the levels of
      FGF2, PDGF-BB, and IL-6 did not differ significantly among the groups.
      CONCLUSIONS: Administration of D2O prevented the development of kaolin-induced
      hydrocephalus in mice and inhibited intrameningeal fibrosis and upregulation of
      TGFbeta1.

PMID- 16619637
TI  - Functional magnetic resonance imaging of the primary somatosensory cortex in
      piglets.
AB  - OBJECT: The piglet is an excellent model for the developing human brain, and has
      been used increasingly in various centers for studies of traumatic brain injury
      and other insults. Unlike rodent or primate models, however, there are few
      behavioral scales for the piglet, and the available ones are used to test general
      responsiveness rather than specific functional outcome. The differing behavioral
      repertoires of animals of different ages provide an additional challenge when age
      dependent injury responses are compared. To overcome these experimental
      limitations of piglets in brain injury research, the authors developed a
      functional magnetic resonance (fMR) imaging paradigm that can be used to track
      recovery in the somatosensory cortex over time in anesthetized animals of
      different ages. METHODS: Fifteen fMR imaging studies in eight piglets were
      performed before and after scaled cortical impact injury to the primary
      somatosensory cortex subserving snout sensation. Specific anesthetic and imaging
      protocols enabled visualization of cortical activation, and comparison with
      somatosensory evoked potentials obtained before and after injury was obtained. A
      piglet brain template for group-level analysis of these data was constructed,
      similar to the fMR imaging techniques used in humans, to allow for group
      comparisons and longitudinal change analysis over time. CONCLUSIONS: Loss of
      function in a specifically traumatized cortical region and its subsequent
      recovery over time can now be demonstrated visually by fMR imaging in the piglet.
      Besides its value in understanding intrinsic recovery mechanisms and plasticity
      at different ages, this functional outcome measure will enable the use of the
      piglet model in treatment trials specifically designed for the immature brain.

PMID- 16619638
TI  - Absence epilepsy associated with moyamoya disease. Case report.
AB  - The authors present the case of a 6-year-old girl with typical absence epilepsy
      induced by hyperventilation associated with moyamoya disease (MMD). A diffuse 3
      Hz spike-and-wave complex induced by hyperventilation was apparent on an
      electroencephalogram, and her seizures were intractable to medication.
      Significant ischemia in the bilateral frontal lobes was present. The epilepsy
      disappeared after superficial temporal artery-middle cerebral artery anastomosis
      with encephalomyosynangiosis on both sides. In the treatment of children with
      intractable absence epilepsy, the possibility of underlying MMD and indications
      that revascularization surgery may be needed should be taken into consideration.

PMID- 16619639
TI  - Holocord intramedullary abscess due to dermal sinus in a 2-month-old child
      successfully treated with limited myelotomy and aspiration. Case report.
AB  - This 2-month-old child presented with paraplegia. The authors observed a dermal
      sinus with purulent discharge in the lumbosacral area. Magnetic resonance (MR)
      imaging of the spine revealed an intramedullary enhancing cavity spanning C-1 to
      the conus medullaris. Intraoperatively the dermal sinus was seen to infiltrate
      the lower end of the conus medullaris, and it also communicated directly with the
      central canal. The L2-5 laminae were removed, and a myelotomy was undertaken on
      the conus medullaris. A No. 8 French pediatric feeding tube was passed into the
      abscess cavity and advanced rostrally to the level of C-1. Aspiration was applied
      via the feeding tube to drain the intramedullary abscess of the spinal cord
      (IASC). Postoperatively, a 6-week course of intravenous cloxacillin was
      instituted. Follow-up MR imaging revealed complete resolution of abscess. When
      the patient was 26 months of age, examination showed complete neurological
      recovery. The authors describe what, to their knowledge, is the first case of a
      holocord IASC treated successfully by the aforementioned technique, and review of
      the related literature.

PMID- 16619640
TI  - Spontaneous involution of a large pineal region hemorrhagic cyst in an infant.
      Case report.
AB  - The authors report the case of a newborn presenting at birth with macrocephaly
      and a large pineal region hemorrhagic cyst without neurological deficit. No
      neurosurgical intervention was performed, and subsequent imaging studies
      demonstrated complete involution of the cyst.

PMID- 16619641
TI  - Cauda equina-penetrating injury in a child. Case report.
AB  - The authors report the case of a 10-year-old boy who sustained an injury to the
      cauda equina as a result of the accidental penetration of a wooden pencil into
      the spinal canal. After neuroimaging evaluation to exclude visceral and vascular
      lesions, the foreign body was removed and the wound was repaired. This is the
      first report of a cauda equina injury caused by a pencil.

PMID- 16619642
TI  - Extruded lumbar disc associated with epidural hematoma. Case report.
AB  - Lumbar disc herniation and spinal epidural hematomas (SEHs) are highly unusual
      causes of secondary lumbar canal stenosis in the adolescent population. The
      authors report a unique concomitant occurrence in a 16-year-old boy who presented
      with left-sided L-5 radiculopathy. Magnetic resonance imaging T1-weighted
      sequences revealed a left-sided posterolateral prolapsed L4-5 disc with an
      isointense extruded fragment lying behind the L-5 body. On T2-weighted sequences
      a hyperintense area was seen in the region of the extruded disc fragment with
      thecal compression. At surgery the extradural encapsulated hematoma was removed,
      together with the extruded disc fragment and the L4-5 disc. The characteristics
      of the biopsy specimen from the epidural collection were consistent with those of
      a hematoma. At 6 months' follow up, the patient had returned to his normal
      activities. An SEH may result from tearing of delicate epidural veins following
      disc extrusion. It can occur at any age, regardless of whether there is a history
      of significant trauma. Magnetic resonance imaging allows preoperative
      characterization of the lesion. Results after surgical evacuation are excellent.
      Distinguishing between a solitary SEH and one caused by a lumbar disc extrusion
      has significant implications, as the former may resolve completely with
      conservative management.

PMID- 16619643
TI  - Intrinsic brainstem epidermoid cyst. Case report and review of the literature.
AB  - Brainstem epidermoid cysts are rare lesions, with only 18 reported cases in the
      literature and only five purely intrinsic epidermoid cysts within this group. The
      authors present the case of a 3-year-old girl with a history of chronic
      headaches, progressive diplopia, and relapsing and remitting mild right
      hemiparesis who was found to harbor an intrinsic brainstem epidermoid cyst at the
      pontomedullary junction. Initial working diagnoses included intrinsic brainstem
      astrocytoma and cavernoma. After tumor enlargement and progressive symptoms, a
      diffusion-weighted (DW) magnetic resonance (MR) imaging sequence was performed
      and a definitive diagnosis of an intrinsic brainstem epidermoid cyst was made in
      the patient. The patient underwent a suboccipital craniotomy and complete
      resection of the cyst with the aid of intraoperative neurophysiological
      monitoring. Three years after the operation, the patient is neurologically intact
      and no evidence of tumor recurrence has been found. The rarity of brainstem
      epidermoid cysts can make their diagnosis difficult; thus a DW MR imaging
      sequence of the brain is a useful diagnostic modality. Intrinsic brainstem
      epidermoid cysts can be removed safely, in a manner similar to that used for the
      surgical treatment of focal tumors.

PMID- 16619644
TI  - Cleidocranial dysplasia in a mother and her daughter within the scope of
      neurosurgery. Report of two cases.
AB  - Cleidocranial dysplasia is an autosomal-dominant disorder characterized by late
      closure or nonclosure of the anterior fontanelle, late ossification of cranial
      sutures, defective clavicle, and delayed eruption of permanent teeth. In this
      article, two cases of cleidocranial dysplasia involving a mother and her daughter
      are reported, and a case management policy is suggested. The 1-year-old daughter
      was macrocephalic and brachycephalic, and had midface hypoplasia and
      hypertelorism. Plain radiographs revealed aplasia of the clavicles. Three
      dimensional computerized tomography scanning demonstrated a large anterior
      fontanelle, a patent posterior fontanelle, and bone defects at the pterion and
      asterion, together with nonfused metopic and sagittal sutures. The mother was 22
      years of age. She had an open anterior fontanelle, aplastic clavicles, and
      unerupted permanent teeth. Although it is a rare disorder, cleidocranial
      dysplasia should be recognized by neurosurgeons. A protective helmet can be
      provided in early childhood, and craniofacial remodeling can be undertaken at a
      later age, when the final size and shape of the skull become apparent.

PMID- 16619645
TI  - Sporadic osteochondroma of the cervical spine. Case illustration.

PMID- 16619646
TI  - Pressure-programmable shunt valves.

PMID- 16619647
TI  - Decompressive craniectomy.

PMID- 16619648
TI  - Outcome following decompressive craniectomy for malignant swelling due to severe
      head injury.
AB  - OBJECT: The aim of this study was to assess outcome following decompressive
      craniectomy for malignant brain swelling due to closed traumatic brain injury
      (TBI). METHODS: During a 48-month period (March 2000-March 2004), 50 of 967
      consecutive patients with closed TBI experienced diffuse brain swelling and
      underwent decompressive craniectomy, without removal of clots or contusion, to
      control intracranial pressure (ICP) or to reverse dangerous brain shifts. Diffuse
      injury was demonstrated in 44 patients, an evacuated mass lesion in four in whom
      decompressive craniectomy had been performed as a separate procedure, and a
      nonevacuated mass lesion in two. Decompressive craniectomy was performed urgently
      in 10 patients before ICP monitoring; in 40 patients the procedure was performed
      after ICP had become unresponsive to conventional medical management as outlined
      in the American Association of Neurological Surgeons guidelines. Survivors were
      followed up for at least 3 months posttreatment to determine their Glasgow
      Outcome Scale (GOS) score. Decompressive craniectomy lowered ICP to less than 20
      mm Hg in 85% of patients. In the 40 patients who had undergone ICP monitoring
      before decompression, ICP decreased from a mean of 23.9 to 14.4 mm Hg (p <
      0.001). Fourteen of 50 patients died, and 16 either remained in a vegetative
      state (seven patients) or were severely disabled (nine patients). Twenty patients
      had a good outcome (GOS Score 4-5). Among 30-day survivors, good outcome occurred
      in 17, 67, and 67% of patients with postresuscitation Glasgow Coma Scale scores
      of 3 to 5, 6 to 8, and 9 to 15, respectively (p < 0.05). Outcome was unaffected
      by abnormal pupillary response to light, timing of decompressive craniectomy,
      brain shift as demonstrated on computerized tomography scanning, and patient age,
      possibly because of the small number of patients in each of the subsets.
      Complications included hydrocephalus (five patients), hemorrhagic swelling
      ipsilateral to the craniectomy site (eight patients), and subdural hygroma (25
      patients). CONCLUSIONS: Decompressive craniectomy was associated with a better
      than-expected functional outcome in patients with medically uncontrollable ICP
      and/or brain herniation, compared with outcomes in other control cohorts reported
      on in the literature.

PMID- 16619649
TI  - Stereoelectroencephalography using computerized tomography- or magnetic resonance
      imaging-guided electrode implantation.

PMID- 16619650
TI  - Efficacy of and morbidity associated with stereoelectroencephalography using
      computerized tomography--or magnetic resonance imaging-guided electrode
      implantation.
AB  - OBJECT: The purpose of this paper was to define the general efficacy of and
      morbidity associated with stereoelectroencephalography using modem methods of
      imaging and to particularize the risks related to specific lobes of the brain.
      METHODS: All patients admitted to the Montreal Neurological Institute who had
      undergone either computerized tomography- or magnetic resonance imaging-guided
      electrode implantation by one surgeon (A.O.) were reviewed. The procedure was
      considered efficient if the obtained information was sufficient to make a
      decision either in support of or against surgery. Two hundred seventeen patients
      underwent 224 implantations with 3022 electrodes. Complications related to each
      lobe were as follows: temporal lobe, two abscesses (0.54%); frontal lobe, one
      abscess and three hematomas (1.4%); and occipital lobe, one hypointense lesion
      found 1 week after electrode explantation (2.6%). Significant risk factors
      associated with hematomas were implantation in the frontal lobe (p < 0.05) and
      the use of four or more implanted electrodes (p < 0.025). General complications
      included the following: 26 patients, psychiatric symptoms during monitoring; one
      patient, meningitis; four patients, scalp cellulitis; and two patients,
      hemiparesis during angiography in the early 1980s. One of these latter patients
      maintained a mild hemiparesis and represents the only case of permanent
      neurological sequela in the entire series. Data obtained during recordings
      supported an indication for surgery in 178 patients (79.5%), excluded a surgical
      option in 37 patients (16.5%), and were unsatisfactory in nine patients (4%).
      Thus, the overall efficacy as defined previously was 96%. CONCLUSIONS:
      Stereoelectroencephalography is an efficient procedure with low associated
      morbidity. Bilateral exploration of the temporal lobes has a morbidity rate of
      approximately 1%. A higher risk of hematomas occurs with the implantation of four
      or more electrodes in the frontal lobes.

PMID- 16619651
TI  - Microelectrode-guided implantation of deep brain stimulators into the globus
      pallidus internus for dystonia: techniques, electrode locations, and outcomes.
AB  - OBJECT: Deep brain stimulation (DBS) of the globus pallidus internus (GPI) is a
      promising new procedure for the treatment of dystonia. The authors describe their
      technical approach for placing electrodes into the GPI in awake patients with
      dystonia, including methodology for electrophysiological mapping of the GPI in
      the dystonic state, clinical outcomes and complications, and the location of
      electrodes associated with optimal benefit. METHODS: Twenty-three adult and
      pediatric patients with various forms of dystonia were included in this study.
      Baseline neurological status and DBS-related improvement in motor function were
      measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The
      implantation of DBS leads was performed using magnetic resonance (MR) imaging
      based stereotaxy, single-cell microelectrode recording, and intraoperative test
      stimulation to determine thresholds for stimulation-induced adverse effects.
      Electrode locations were measured on computationally reformatted postoperative MR
      images according to a prospective protocol. CONCLUSIONS: Physiologically guided
      implantation of DBS electrodes in patients with dystonia was technically feasible
      in the awake state in most patients, and the morbidity rate was low. Spontaneous
      discharge rates of GPI neurons in dystonia were similar to those of globus
      pallidus externus neurons, such that the two nuclei must be distinguished by
      neuronal discharge patterns rather than rates. Active electrode locations
      associated with robust improvement (> 70% decrease in BFMDRS score) were located
      near the intercommissural plane, at a mean distance from the pallidocapsular
      border of 3.6 mm.

PMID- 16619652
TI  - Effects of bilateral subthalamic nucleus stimulation on sleep, daytime
      sleepiness, and early morning dystonia in patients with Parkinson disease.
AB  - OBJECT: The aim of this study was to assess the long-term effects of bilateral
      deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson
      disease (PD) on sleep, daytime sleepiness, and early morning dystonia and to
      evaluate the relationship between total sleep time and motor function. METHODS:
      Patients who had undergone bilateral STN DBS and a follow-up evaluation of 6
      months (89 patients), 12 months (83 patients), and 24 months (43 patients) were
      included in this study. The patients were preoperatively assessed using the
      Unified Parkinson's Disease Rating Scale (UPDRS) in the medication-on and -off
      conditions, and they completed patient diaries. A subset of patients also
      completed the Epworth Sleepiness Scale. These assessments were repeated
      postoperatively with stimulation. The UPDRS activities of daily living (ADL) and
      motor scores as well as total sleep hours were significantly improved at 6, 12,
      and 24 months poststimulation and with no medication compared with baseline
      values. Increased sleep time was significantly correlated with improvements in
      bradykinesia but not with tremor or rigidity. Patient-reported sleep problems and
      early morning dystonia were reduced after STN DBS. Antiparkinsonian medications
      were significantly reduced after STN DBS; however, there were no changes in
      excessive daytime sleepiness 6, 12, or 24 months after surgery. CONCLUSIONS:
      Bilateral STN DBS increased total sleep time and reduced patient-reported sleep
      problems and early morning dystonia for up to 24 months posttreatment. These
      changes in sleep were related to improvements in functioning, specifically those
      affected by bradykinesia. Despite significant reductions in antiparkinsonian
      medications, STN DBS did not reduce excessive daytime sleepiness.

PMID- 16619653
TI  - Long-term evaluation of deep brain stimulation of the thalamus.
AB  - OBJECT: The effects of thalamic deep brain stimulation (DBS) on essential tremor
      (ET) and Parkinson disease (PD) have been well documented, but there is a paucity
      of long-term data. The aim of this study was to evaluate the long-term safety and
      efficacy of DBS of the ventralis intermedius nucleus (VIM) of the thalamus for PD
      and ET. METHODS: Thirty-eight of 45 patients enrolled at five sites completed a 5
      year follow-up study. There were 26 patients with ET and 19 with PD undergoing 29
      unilateral (18 ET/11 PD) and 16 bilateral (eight ET/eight PD) procedures.
      Patients with ET were evaluated using the Tremor Rating Scale, and patients with
      PD were evaluated using the Unified Parkinson's Disease Rating Scale. The mean
      age of patients with ET was 70.2 years and 66.3 years in patients with PD.
      Unilaterally implanted patients with ET had a 75% improvement of the targeted
      hand tremor; those with bilateral implants had a 65% improvement in the left hand
      and 86% in the right compared with baseline. Parkinsonian patients with
      unilateral implants had an 85% improvement in the targeted hand tremor and those
      with bilateral implants had a 100% improvement in the left hand and 90%
      improvement in the right. Common DBS-related adverse events in patients receiving
      unilateral implants were paresthesia (45%) and pain (41%), and in patients
      receiving implants bilaterally dysarthria (75%) and balance difficulties (56%)
      occurred. Device-related surgical revisions other than IPG replacements occurred
      in 12 (27%) of the 45 patients. CONCLUSIONS: Thalamic stimulation is safe and
      effective for the long-term management of essential and Parkinsonian tremors.
      Bilateral stimulation can cause dysarthria and incoordination and should be used
      cautiously.

PMID- 16619654
TI  - Long-term outcome of epilepsy surgery among 399 patients with nonlesional seizure
      foci including mesial temporal lobe sclerosis.
AB  - OBJECT: The authors reviewed the long-term outcome of focal resection in a large
      group of patients who had intractable partial nonlesional epilepsy, including
      mesial temporal lobe sclerosis (MTS), and who were treated consecutively at a
      single institution. The goal of this study was to evaluate the long-term efficacy
      of epilepsy surgery and the preoperative factors associated with seizure outcome.
      METHODS: This retrospective analysis included 399 consecutive patients who
      underwent epilepsy surgery at Mayo Clinic in Rochester, Minnesota, between 1988
      and 1996. The mean age of the patients at surgery was 32 +/- 12 years (range 3-69
      years), and the mean age at seizure onset was 12 +/- 11 years (range 0-55 years).
      There were 214 female (54%) and 185 male (46%) patients. The mean duration of
      epilepsy was 20 +/- 12 years (range 1-56 years). The preceding values are given
      as the mean +/- standard deviation. Of the 399 patients, 237 (59%) had a history
      of complex partial seizures, 119 (30%) had generalized seizures, 26 (6%) had
      simple partial seizures, and 17 (4%) had experienced a combination of these.
      Preoperative evaluation included a routine and video-electroencephalography
      recordings, magnetic resonance imaging of the head according to the seizure
      protocol, neuropsychological testing, and a sodium amobarbital study. Patients
      with an undefined epileptogenic focus and discordant preoperative studies
      underwent an intracranial study. The mean duration of follow up was 6.2 +/- 4.5
      years (range 0.6-15.7 years). Seizure outcome was categorized based on the
      modified Engel classification. Time-to-event analysis was performed using Kaplan
      Meier curves and Cox regression models to evaluate the risk factors associated
      with outcomes. Among these patients, 372 (93%) underwent temporal and 27 (7%) had
      extratemporal resection of their epileptogenic focus. Histopathological
      examination of the resected specimens revealed MTS in 113 patients (28%), gliosis
      in 237 (59%), and normal findings in 49 (12%). Based on the Kaplan-Meier
      analysis, the probability of an Engel Class I outcome (seizure free, auras, or
      seizures related only to medication withdrawal) for the overall patient group was
      81% (95% confidence interval [CI] 77-85%) at 6 months, 78% (CI 74-82%) at 1 year,
      76% (CI 72-80%) at 2 years, 74% (CI 69-78%) at 5 years, and 72% (CI 67-77%) at 10
      years postoperatively. The rate of Class I outcomes remained 72% for 73 patients
      with more than 10 years of follow up. If a patient was in Class I at 1 year
      postoperatively, the probability of seizure remission at 10 years postoperatively
      was 92% (95% CI 89-96%); almost all seizures occurred during the 1st year after
      surgery. Factors predictive of poor outcome from surgery were normal pathological
      findings in resected tissue (p = 0.038), male sex (p = 0.035), previous surgery
      (p < 0.001), and an extratemporal origin of seizures (p < 0.001). CONCLUSIONS:
      The response to epilepsy surgery during the 1st follow-up year is a reliable
      indicator of the long-term Engel Class I postoperative outcome. This finding may
      have important implications for patient counseling and postoperative
      discontinuation of anticonvulsant medications.

PMID- 16619655
TI  - The physical performance test and the evaluation of functional status in patients
      with cerebral aneurysms.
AB  - OBJECT: Cerebral aneurysms can adversely affect the functional status of patients
      who harbor them through rupture, mass effect, or treatment sequela. The authors
      compared the Physical Performance Test (PPT)--an observer-administered test
      requiring the completion of seven tasks--with three functional status measures
      based on patient self-reports: the Glasgow Outcome Scale (GOS), the modified
      Rankin Scale (mRS), and the modified Barthel Index (mBI). METHODS: Data were
      collected from 144 patients with aneurysms who had been recruited from a
      neurosurgery clinic. The patients completed the PPT and were assigned GOS scores,
      mRS scores, and mBIs based on their responses during a structured interview. The
      validity of the PPT was assessed by examining the relationship between the
      results of the PPT and the values assigned to each patient by using the GOS, mRS,
      and mBI by applying rank-order methods; the reliability of the PTT was assessed
      using the Cronbach alpha coefficient. The mean age of the patients was 52.8
      years; 72% were women and 54% had survived a subarachnoid hemorrhage. The mean +/
      standard deviation PPT score was 24.0 +/- 3.7. The PPT generated a broad
      distribution of scores, whereas GOS and mRS scores and mBIs displayed significant
      ceiling effects, that is, 75% of the patients were clustered in the highest
      categories. The PPT scores were validated by their strong association with GOS
      scores, mRS scores, and mBIs (for all, p < 0.001), and the reliability of the PPT
      was demonstrated by a Cronbach alpha value of 0.77. CONCLUSIONS: The PPT provides
      an objective measure of functional status in patients with cerebral aneurysms.
      The results suggest that the PPT may differentiate among patients better than the
      GOS, mRS, or mBL The PPT is a valid and reliable instrument for measuring
      functional status in patients with cerebral aneurysms.

PMID- 16619656
TI  - Use of antihypertension agents for the suppression of arterial pulse pressure
      waveforms in patients with intracranial aneurysms.
AB  - OBJECT: Patients with intracranial aneurysms tend toward raised blood pressure
      and abnormal pulse pressure profiles. The authors have investigated the influence
      of three antihypertension agents on blood pressure and pulse pressure waveforms
      in patients with known intracranial aneurysms, with a view to assessing the
      potential benefits of longterm antihypertension therapy on the progression of
      unruptured intracranial aneurysms. METHODS: Nineteen patients with a mean age of
      56 years (range 38-76 years) were recruited for this study. All patients had
      confirmed intracranial aneurysms. A double-blind, randomized, crossover study was
      performed using perindopril, irbesartan, isosorbide mononitrate, and a placebo.
      Blood pressure and pulse pressure waveforms were assessed at the end of each 4
      week treatment period. Perindopril and irbesartan were well tolerated. For all
      measured parameters except heart rate (p = 0.03), no significant difference
      between baseline and placebo was identified. Each drug when compared with placebo
      reduced peripheral arterial blood pressure. Perindopril significantly decreased
      mean blood pressure by 10 mm Hg (p = 0.004), irbesartan by 9 mm Hg (p = 0.004),
      and isosorbide mononitrate by 13 mm Hg (p = 0.005). The administration of each
      drug effected a significant reduction in the carotid artery augmentation index
      (AIX) compared with baseline values (perindopril p = 0.01, irbesartan p = 0.0002,
      and isosorbide mononitrate p = 0.03). There was also a significant difference in
      the AIX between irbesartan and the placebo (p = 0.05). Compared with the placebo,
      there was a significant difference in AIX (adjusted for heart rate) following the
      administration of irbesartan (p = 0.003) and isosorbide mononitrate (p = 0.01),
      but not with perindopril (p = 0.17). CONCLUSIONS: Irbesartan appears to be the
      most effective treatment for the combined suppression of blood pressure and AIX
      in patients with intracranial aneurysms and has a high degree of patient
      tolerance.

PMID- 16619657
TI  - Modification of glucose metabolism in brain tumors by using cervical spinal cord
      stimulation.
AB  - OBJECT: In previous studies the authors have shown potential increases in
      locoregional blood flow and oxygenation in tumors by using electrical cervical
      spinal cord stimulation (SCS). In the present report they demonstrate the effect
      of cervical SCS on brain tumor metabolism, as assessed using
      [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET). METHODS: Cervical
      devices were inserted in 11 patients who had high-grade gliomas, six of which had
      recurred. While the SCS device was deactivated, each patient underwent an initial
      FDG-PET study to clarify the clinical status. A second FDG-PET study was
      performed later the same day while the stimulation device was activated to
      determine the effect of cervical SCS on glucose metabolism. All 11 patients were
      invaluable for this PET study. Basal glucose metabolism was higher in the tumor
      than in the peritumoral areas (p = 0.048). There was a significant increase in
      glucose uptake during cervical SCS in both the tumor (p = 0.035) and the
      peritumoral (p = 0.001) areas, with measured increases of 43 and 38%,
      respectively. The estimated potential maximal residual activity of the first FDG
      dose's contribution to the activity on the second scan was 18.5 +/- 1% or less.
      CONCLUSIONS: This PET study is the first in which is described the effect of
      cervical SCS on glucose metabolism in brain tumors and supports previous study
      data indicating a modification of locoregional blood flow and oxygenation by
      cervical SCS. These results open up new approaches to modifying the effect of
      radiochemotherapy in the treatment of malignant brain tumors.

PMID- 16619658
TI  - The impact of genotype on outcome in oligodendroglioma: validation of the loss of
      chromosome arm 1p as an important factor in clinical decision making.
AB  - OBJECT: Oligodendrogliomas are rare primary brain tumors. They comprise
      approximately 5 to 33% of all glial tumors but differ from astrocytomas by being
      associated with a more favorable prognosis, making their correct identification
      important. Allelic loss of chromosome arms 1p and 19q is found in a substantial
      subpopulation of tumors with an oligodendroglioma phenotype. Anaplastic
      oligodendrogliomas with allelic loss of 1p have been associated with
      chemosensitivity and a longer patient survival period. METHODS: Oligodendroglial
      neoplasms were studied using fluorescence in situ hybridization of formalin
      fixed, paraffin-embedded tissue specimens; reference and target probe sets were
      used to map the telomeric regions of 1p and 19q. The results were correlated with
      the clinical characteristics of patients treated at our institution between 1993
      and 2003. Data obtained in 96 patients were analyzed. This included 63 patients
      (65.6%) with World Health Organization (WHO) Grade II oligodendroglioma, 22 (23%)
      with Grade III oligodendroglioma, and 11 (11.4%) with mixed oligoastrocytoma.
      Analysis of 1p in patients with pure oligodendroglioma revealed a loss of 1p in
      42 patients (49.4%). In 46 of these patients 19q was lost and in 70 (82.3%) there
      was concordance for combined loss or retention of both 1p and 19q (p < 0.0001).
      Patients with oligodendroglioma in whom a loss of 1p was present fared
      significantly better, and this outcome was unrelated to the treatment modality or
      WHO grade, compared with patients in whom 1p was intact (p < 0.05). CONCLUSIONS:
      To the authors' knowledge, this study includes the largest published series of
      WHO Grade II oligodendroglioma and 1p analysis. The results suggest that the
      association between long-term survival and 1p loss in oligodendroglioma is
      unrelated to treatment. The authors of further prospective studies may better
      determine the true value of the allelic loss of 1p and its implication for
      clinical decision making.

PMID- 16619659
TI  - Suprascapular intraneural ganglia and glenohumeral joint connections.
AB  - OBJECT: Unlike the more commonly noted paralabral cysts (extraneural ganglia),
      which are well known to result in suprascapular nerve compression, only four
      cases of suprascapular intraneural ganglia have been reported. Because of their
      rarity, the pathogenesis of suprascapular intraneural ganglia has been poorly
      understood and a pathoanatomical explanation has not been provided. In view of
      the growing literature demonstrating strong associations between paralabral cysts
      and labral (capsular) pathology, joint connections, and joint communications, the
      authors retrospectively reviewed the magnetic resonance (MR) imaging studies and
      postoperative results in the two featured patients to test a hypothesis that
      suprascapular intraneural ganglia would have analogous findings. METHODS: Two
      patients who presented with suprascapular neuropathy were found to have
      intraneural ganglia. Connections to the glenohumeral joint could be established
      in both patients through posterior labrocapsular complex tears. In neither
      patient was the joint connection identified preoperatively or intraoperatively,
      and cyst decompression was performed by itself without attention to the labral
      tear. The suprascapular intraneural ganglia extended from the glenohumeral joint
      as far proximally as the level of the nerves' origin from the upper trunk in the
      supraclavicular fossa. Although both patients experienced symptomatic improvement
      after surgery, neurological recovery was incomplete. In both cases, postoperative
      MR images revealed cyst persistence. In addition, previously unrecognized
      superior labral anteroposterior (SLAP) Type II lesions (tears of the superior
      labrum extending anteroposterior and involving the biceps anchor at the labrum
      without actual extension into the tendon) were visualized. In one patient with a
      persistent cyst, an MR arthrogram was obtained and demonstrated a communication
      between the joint and the cyst. CONCLUSIONS: The findings in these two patients
      support the synovial theory for intraneural ganglia. Based on their experience
      with intraneural ganglia at other sites, the authors believe that suprascapular
      intraneural ganglia arise from the glenohumeral joint, egress through a superior
      (posterior) labral tear, and dissect within the epineurium along an articular
      branch into the main nerve, following the path of least resistance. Furthermore,
      these two cases of intraneural ganglia with SLAP lesions are directly analogous
      to the many cases of paralabral cysts associated with these types of labral
      tears. By better understanding the origin of this unusual type of ganglia and
      drawing analogies to the more common extraneural cysts, surgical strategies can
      be formulated to address the underlying pathoanatomy, improve operative outcomes,
      and prevent recurrences.

PMID- 16619660
TI  - A functional neuroimaging investigation of deep brain stimulation in patients
      with obsessive-compulsive disorder.
AB  - OBJECT: Deep brain stimulation (DBS) of the ventral [anterior internal]
      capsule/ventral striatum (VC/VS) is under investigation as an alternative to
      anterior capsulotomy for severe obsessive-compulsive disorder (OCD). In
      neuroimaging studies of patients with OCD, dysfunction in the orbitofrontal and
      anterior cingulate cortex, striatum, and thalamus has been identified; and
      modulation of activity in this circuit has been observed following successful
      nonsurgical treatment. The purpose of the current study was to test hypotheses
      regarding changes in regional cerebral blood flow (rCBF) during acute DBS at the
      VC/VS target in patients with OCD who were participating in a clinical DBS trial.
      METHODS: Six patients enrolled in a DBS trial for OCD underwent positron emission
      tomography to measure rCBF; the rCBF measured during acute DBS at high frequency
      was then compared with those measured during DBS at low frequency and off
      (control) conditions. On the basis of neuroanatomical knowledge about the VC/VS
      and neuroimaging data on OCD, the authors predicted that acute DBS at this target
      would result in modulation of activity within the implicated frontal-basal
      ganglia-thalamic circuit. Data were analyzed using statistical parametric
      mapping. In a comparison of acute high-frequency DBS with control conditions, the
      authors found significant activation of the orbitofrontal cortex, anterior
      cingulate cortex, striatum, globus pallidus, and thalamus. CONCLUSIONS: Acute DBS
      at the VC/VS target is associated with activation of the circuitry implicated in
      OCD. Further studies will be necessary to replicate these findings and to
      determine the neural effects associated with chronic VC/VS DBS. Moreover,
      additional data are needed to investigate whether pretreatment imaging profiles
      can be used to predict a patient's subsequent clinical response to chronic DBS.

PMID- 16619661
TI  - Preoperative endovascular brain mapping for intraoperative volumetric image
      guidance: preliminary concept and feasibility in animal models.
AB  - OBJECT: The authors describe a novel concept for brain mapping in which an
      endovascular approach is used, and they demonstrate its feasibility in animal
      models. The purpose of endovascular brain mapping is to delineate clearly the
      nonfunctional brain parenchyma when a craniotomy is performed for resection. The
      nonfunctional brain will be stained with sharp visual margins, differentiating it
      from the functional, nonstained brain. The authors list four essential criteria
      for developing an ideal endovascular mapping agent, and they describe seven
      potential approaches for accomplishing a successful endovascular brain map.
      METHODS: Four Sprague-Dawley rats and one New Zealand white rabbit were used to
      determine initial feasibility of the procedure. The animals were anesthetized,
      and the internal carotid artery was catheterized. Four potential brain mapping
      agents were infused into the right hemisphere of the five animals. Afterward, the
      brains were removed and each was analyzed both grossly and histologically.
      Fluorescein and FD&C Green No. 3 provided good visual clarity and margins, but
      required blood-brain barrier (BBB) manipulation. Tantalum particles enabled
      avoidance of BBB manipulation, but provided inadequate visual clarity, probably
      because of their size. A Sudan black "cocktail" provided excellent clarity and
      margins despite remaining in the brain capillaries. CONCLUSIONS: This is a novel
      application of the endovascular approach, and has broad potential for clinical
      neurosurgical brain mapping. The animal models in this study establish the
      feasibility of the procedure. However, further study is required to demonstrate
      safety, minimize toxicity, investigate stain durability, and improve the
      characteristics of potential mapping agents. The authors are planning to conduct
      future studies for identification of mapping agents that do not require BBB
      manipulation or vascular occlusion.

PMID- 16619662
TI  - Induction of macrophagic prostaglandin E2 synthesis by glioma cells.
AB  - OBJECT: It has been reported that glioma cells produce prostaglandin (PG)E2,
      which promotes the growth of tumor cells and possesses immunosuppressive
      activity, and that cyclooxygenase (COX) inhibitors impede tumor growth and
      infiltration. Macrophages in tumor-bearing hosts are activated to produce PGE2,
      which induces an immunosuppressive state. Note, however, that the precise
      mechanism by which PGE2 induces an immunosuppressive state is still unclear. In
      this study, the authors investigated the mechanism of PGE2 production in glioma
      bearing hosts. METHODS: The human and murine glioma cells that were studied did
      not produce a significant amount of PGE2. However, the coculture of human
      peripheral blood mononuclear cells or murine peritoneal macrophages with glioma
      cells or conditioned glioma medium led to the production of a large amount of
      PGE2. In contrast, production of tumor necrosis factor and interleukin (IL)-12p70
      by macrophages and cytotoxic T lymphocyte induction were suppressed by culturing
      with conditioned glioma medium; this suppression was abrogated by the addition of
      the COX inhibitor indomethacin. The macrophagic expression of COX-2, and
      particularly the expression of microsomal PGE synthase (mPGES)-1, a terminal
      enzyme of the arachidonate cascade, was enhanced by the glioma-derived soluble
      factors. Furthermore, IL-12p70 production was not clearly suppressed in
      macrophages from mPGES-1-deficient mice. The glioma-derived soluble factors were
      sensitive to treatment with heat and papain. CONCLUSIONS: These results indicated
      that PGE2 production by macrophages is enhanced by glioma-derived soluble
      factors, which induce an immunosuppressive state in glioma-bearing hosts.
      Therefore, the inhibition of PGE2 synthesis, targeting COX-2 and mPGES-1, is an
      effective treatment for the induction of antiglioma immune responses.

PMID- 16619663
TI  - The human survivin promoter: a novel transcriptional targeting strategy for
      treatment of glioma.
AB  - OBJECT: Malignant brain tumors have been proved to be resistant to standard
      treatments and therefore require new therapeutic strategies. Survivin, a recently
      described member of the inhibitor of apoptosis protein family, is overexpressed
      in several human brain tumors, primarily gliomas, but is downregulated in normal
      tissues. The authors hypothesized that the expression of tumor-specific survivin
      could be exploited for treatment of gliomas by targeting the tumors with gene
      therapy vectors. METHODS: Following confirmation of survivin expression in glioma
      cell lines, an adenoviral vector containing the survivin promoter and the
      reporter gene luciferase was tested in established and primary glioma cells,
      normal astrocytic cells, and normal human brain tissues. High levels of reporter
      gene expression were observed in established tumor and primary tumor cell lines
      and low levels of expression in astrocytes and normal human brain tissue. To test
      oncolytic potency, the authors constructed survivin promoter-based conditionally
      replicative adenoviruses (CRAds), composed of survivin promoter-regulated E1 gene
      expression and an RGD-4C capsid modification. These CRAds could efficiently
      replicate within and kill a variety of established glioma tumor cells, but were
      inactive in a normal human liver organ culture. Finally, survivin promoter-based
      CRAds significantly inhibited the growth of glioma xenografts in vivo.
      CONCLUSIONS: Together these data indicate that the survivin promoter is a
      promising tumor-specific promoter for transcriptional targeting of adenovirus
      based vectors and CRAds for malignant gliomas. The strategy of using survivin
      CRAds may thus translate into an experimental therapeutic approach that can be
      used in human clinical trials.

PMID- 16619664
TI  - Intraorbital implantation of a stimulating electrode for an optic nerve visual
      prosthesis. Case report.
AB  - Research into visual prosthetics is expected to revolutionize the treatment of
      blind patients with incurable outer retinal degenerative disease. Substantial
      evidence shows that useful visual sensations can be produced by controlled
      electrical stimulation of the optic nerve. To make the optic nerve visual
      prosthesis more acceptable, implantation techniques safer and less invasive than
      those previously used have been developed. A medial transconjunctival approach is
      now used to implant a stimulating electrode around the intraorbital section of
      the optic nerve. This new technique allows sufficient exposure of the nerve after
      detaching only one rectus muscle and performing a lateral canthotomy. Previously,
      an electrode was implanted in the intracranial part of the optic nerve, which
      required more invasive surgery. The new technique was first developed in cadavers
      and in patients undergoing eye enucleations. Finally, a 68-year-old blind man
      suffering from retinitis pigmentosa underwent long-term implantation. In this
      case report the authors describe the technique and outline some of the challenges
      involved.

PMID- 16619665
TI  - Dissociated expressive and receptive language functions on
      magnetoencephalography, functional magnetic resonance imaging, and amobarbital
      studies. Case report and review of the literature.
AB  - Dissociated language functions are largely invalidated by standard techniques
      such as the amobarbital test and cortical stimulation. Language studies in which
      magnetoencephalography (MEG) and functional magnetic resonance (fMR) imaging are
      used to record data while the patient performs lexicosemantic tasks have enabled
      researchers to perform independent brain mapping for temporal and frontal
      language functions (MEG is used for temporal and fMR imaging for frontal
      functions). In this case report, the authors describe a right-handed patient in
      whom a right-sided insular glioma was diagnosed. The patient had a right
      lateralized receptive language area, but expressive language function was
      identified in the left hemisphere on fMR imaging- and MEG-based mapping.
      Examinations were performed in 20 right-handed patients with low-grade gliomas
      (control group) for careful comparison with and interpretation of this patient's
      results. In these tests, all patients were asked to generate verbs related to
      acoustically presented nouns (verb generation) for fMR imaging, and to categorize
      as abstract or concrete a set of visually presented words consisting of three
      Japanese letters for fMR imaging and MEG. The most prominent display of fMR
      imaging activation by the verb-generation task was observed in the left inferior
      and middle frontal gyri in all participants, including the patient presented
      here. Estimated dipoles identified with the abstract/concrete categorization task
      were concentrated in the superior temporal and supramarginal gyri in the left
      hemisphere in all control patients. In this patient, however, the right superior
      temporal region demonstrated significantly stronger activations on MEG and fMR
      imaging with the abstract/concrete categorization task. Suspected dissociation of
      the language functions was successfully mapped with these two imaging modalities
      and was validated by the modified amobarbital test and the postoperative
      neurological status. The authors describe detailed functional profiles obtained
      in this patient and review the cases of four previously described patients in
      whom dissociated language functions were found.

PMID- 16619666
TI  - Dural plasmacytoma revealing multiple myeloma. Case report.
AB  - The authors describe the case of a 72-year-old woman with dural plasmacytoma
      revealing an immunoglobulin (Ig) G-kappa multiple myeloma (MM). She presented
      with headaches and left hemiparesis. Magnetic resonance imaging demonstrated a
      right frontal extraaxial lesion arising from the dura mater, and biological
      studies revealed hypercalcemia, hyperproteinemia, and a serum gamma globulin
      peak. A diagnosis of IgG-kappa MM was based on microscopic examination and
      immunohistochemical analysis of the dural plasmacytoma as well as on signs of
      systemic myeloma after surgery. The patient died 3 years after the first symptoms
      of MM despite systemic chemotherapy and no recurrence of the dural plasmacytoma.
      Myelomatous involvement of the dura mater is a rare occurrence given that only
      three cases have been reported to date. Nevertheless, this pathological entity
      should be differentiated from solitary dural plasmacytoma (SDP) because the
      prognosis is radically different. Progression seems to be correlated with
      systemic disease in contrast to the long-term survival associated with SDP.
      Careful systemic evaluation should be made in such a presentation to rule out MM,
      which would require different management and has a different prognosis.

PMID- 16619667
TI  - Cranial surgery with an expanded compact intraoperative magnetic resonance
      imager. Technical note.
AB  - In this article the authors report the implementation of an expanded compact
      intraoperative magnetic resonance (iMR) imager that is designed to overcome
      significant limitations of an earlier unit. The PoleStar N20 iMR imager has a
      stronger magnetic field than its predecessor (0.15 tesla compared with 0.12
      tesla), a wider gap between magnet poles, and an ergonomically improved gantry
      design. The additional time needed in the operating room (OR) for use of iMR
      imaging and the number of sessions per patient were recorded. Stereotactic
      accuracy of the integrated navigational tool was assessed using a water-covered
      phantom. Of the 55 patients who have undergone surgery in the PoleStar N20
      device, diagnoses included glioma in 13, meningioma in 12, pituitary adenoma in
      nine, other skull base lesions in seven, and miscellaneous other diagnoses. The
      extra time required for use of the system averaged 1.1 hours (range 0.5-2 hours).
      Imaging sessions averaged 2.3 per surgery (range one-six sessions). Measurement
      of stereotactic accuracy revealed that T1-weighted images were the most accurate.
      Thinner slices yielded measurably greater accuracy, although this was of
      questionable clinical significance (all sequences < or =4 mm had a mean error of
      < or = 1.8 mm). The position of the phantom in the center compared with the
      periphery of the magnetic field did not affect accuracy (mean error 0.9 mm for
      each). The PoleStar N20 appears to make intraoperative neuroimaging with a low
      field-strength magnet much more practical than it was with the first-generation
      device. Greater ease of positioning resulted in a decrease in added time in the
      OR and encouraged a larger number of imaging sessions.

PMID- 16619668
TI  - Possibility of using laser spectroscopy for the intraoperative detection of
      nonfluorescing brain tumors and the boundaries of brain tumor infiltrates.
      Technical note.
AB  - The response of nonfluorescing infiltrating tumors that had been exposed to 5
      aminolevulinic acid and irradiated using a laser at a wavelength of 405 nm was
      analyzed intraoperatively using spectroscopy. Histological analyses demonstrated
      that neoplastic cells were present in the tissue region that displayed a peak at
      636 nm, whereas no neoplastic cells were present in the region that exhibited
      only the excitation light peak. The authors conclude that the intraoperative use
      of laser spectroscopy can allow the diagnosis of infiltrating tumor and the
      detection of boundaries of the infiltrate when standard fluorescence techniques
      fail.

PMID- 16619669
TI  - Ultrasonic bone curettage for optic canal unroofing and anterior clinoidectomy.
      Technical note.
AB  - Extradural unroofing of the optic canal and subsequent mobilization of the optic
      nerve is a useful technique in the surgical treatment of parasellar tumors;
      however, the drilling procedure itself is associated with the risk of optic nerve
      damage. A safer technique would certainly be beneficial. The ultrasonic bone
      curette is a device developed in Japan for safer bone removal. Its use in
      intradural anterior clinoidectomy and opening of the internal auditory meatus has
      been reported before. In this article the authors describe their experience in
      using this device for extradural unroofing of the optic canal in patients with
      parasellar tumors. Between March 2002 and November 2004, the aforementioned
      technique was used in the treatment of eight patients with parasellar tumors.
      After undertaking a frontotemporal craniotomy and orbital osteotomy, an
      ultrasonic bone curette was used to unroof the optic canal via an epidural
      approach; in five cases anterior clinoidectomy was added subsequently. Using an
      ultrasonic bone curette, unroofing of the optic canal was completed safely and
      required much less expertise than that required for standard drilling. The
      mortality and major morbidity rates were 0%. The visual function outcome was
      satisfactory, with the overall visual status improving in all seven patients in
      whom this symptom was present preoperatively. The ultrasonic bone curette makes
      the unroofing of the optic canal safer and easier, possibly improving the visual
      outcome of patients undergoing surgery for parasellar tumors.

PMID- 16619670
TI  - Ulnar nerve volar to medial epicondyle: an anatomical variation. Case
      illustration.

PMID- 16619671
TI  - Historical vignette. Dominique Anel: father of the Hunterian ligation?
AB  - On December 12, 1785, the famous British surgeon John Hunter ligated an artery
      that was feeding a popliteal aneurysm. During the procedure he ligated only the
      proximal side of the artery and left the aneurysm sac untouched. This is
      frequently viewed as a landmark event in the history of surgery. There is
      considerable evidence, however, that another surgeon, Dominique Anel, performed a
      substantially similar procedure more than 75 years earlier. It is possible that
      the weight Hunter's name has borne in the history of surgery has led to the
      procedure's bearing his name rather than that of the lesser known Anel.

PMID- 16619672
TI  - Effect of approach side during anterior cervical discectomy and fusion on the
      incidence of recurrent laryngeal nerve injury.
AB  - OBJECT: This retrospective study was designed to determine whether side of
      approach during instrumented, one- or two-level primary anterior cervical
      discectomy and fusion (ACDF) affects the incidence of recurrent laryngeal nerve
      (RLN) injury diagnosed by observation of the vocal cords (OVC). METHODS: Records
      of all patients who underwent one- or two-level instrumented primary ACDF (418
      patients) between January 1995 and February 2004 were reviewed. Data collected
      from these charts included surgeon, patient demographics, preoperative diagnosis,
      side of exposure, number of vertebral levels fused, and presence of RLN injury
      diagnosed by OVC after referral for persistent dysphonia. Time from surgery to
      OVC for patients with right-sided exposures was not statistically different from
      that for patients with left-sided exposures. Of 418 patients, 278 (66.5%) had
      right-sided exposures and 140 (33.5%) had left-sided exposures. Eight RLN
      injuries (1.9%) were noted-five in patients with right-sided exposures (1.8%) and
      three in patients with left-sided exposures (2.1%). The difference between right-
      and left-sided injury rates was shown to be nonsignificant using Fisher exact
      tests. CONCLUSIONS: Results indicate that, given the study's sample size, side of
      approach during instrumented, one- or two-level primary ACDF has no significant
      effect on RLN injury incidence in patients with persistent dysphonia referred for
      OVC. The definitive answer regarding the true incidence of RLN injury relative to
      approach side awaits a prospective study with preoperative, immediate
      postoperative, and periodic OVC in a large, homogeneous population with
      sufficient numbers of patients with right- and left-sided approaches.

PMID- 16619673
TI  - Regional instability following cervicothoracic junction surgery.
AB  - OBJECT: The cervicothoracic junction (CTJ) is the transitional region between the
      cervical and thoracic sections of the spinal axis. Because it is a transitional
      zone between the mobile lordotic cervical and rigid kyphotic thoracic spines, the
      CTJ is a region of potential instability. This potential for instability may be
      exaggerated by surgical intervention. METHODS: A retrospective review of all
      patients who underwent surgery involving the CTJ in the Department of
      Neurosurgery at the Cleveland Clinic Foundation during a 5-year period was
      performed. The CTJ was strictly defined as encompassing the C-7 vertebra and C7
      T1 disc interspace. Patients were examined after surgery to determine if
      treatment had failed. Failure was defined as construct failure, deformity
      (progression or de novo), or instability. Variables possibly associated with
      treatment failure were analyzed. Statistical comparisons were performed using the
      Fisher exact test. Between January 1998 and November 2003, 593 CTJ operations
      were performed. Treatment failed in 14 patients. Of all variables studied,
      failure was statistically associated with laminectomy and multilevel ventral
      corpectomies with fusion across the CTJ. Other factors statistically associated
      with treatment failure included histories of cervical surgery, tobacco use, and
      surgery for the correction of deformity. CONCLUSIONS: The CTJ is a vulnerable
      region, and this vulnerability is exacerbated by surgery. Results of the present
      study indicate that laminectomy across the CTJ should be supplemented with
      instrumentation (and fusion). Multilevel ventral corpectomies across the CTJ
      should also be supplemented with dorsal instrumentation. Supplemental
      instrumentation should be considered for patients who have undergone prior
      cervical surgery, have a history of tobacco use, or are undergoing surgery for
      deformity correction.

PMID- 16619674
TI  - Expandable cylindrical cages in the cervical spine: a review of 22 cases.
AB  - OBJECT: Expandable cylindrical cages (ECCs) have been utilized successfully to
      reconstruct the thoracic and lumbar spine. Their advantages include ease of
      insertion, reduced endplate trauma, direct application/maintenance of interbody
      distraction force, and one-step kyphosis correction. The authors present their
      experience with ECCs in the reconstruction of the cervical spine in patients with
      various pathological conditions. METHODS: Data obtained in 22 patients were
      reviewed retrospectively. A standard anterior cervical corpectomy was performed
      in all cases. Local vertebral body bone was harvested for use as graft material.
      Patients underwent pre- and postoperative assessment involving the visual analog
      scale (VAS), Nurick grading system for determining myelopathy disability, and
      radiographic studies to determine cervical kyphosis/lordosis and cage subsidence.
      Fusion was defined as the absence of motion on flexion-extension x-ray films.
      Sixteen patients presented with spondylotic myelopathy, two with osteomyelitis,
      two with fracture, one with tumor metastasis, and one with severe stenosis.
      Fourteen patients underwent supplemental posterior spinal fusion, seven underwent
      single-level corpectomy, and 15 patients underwent multilevel corpectomy. No
      perioperative complications occurred. The mean follow-up period was 22 months. In
      11 patients with preexisting kyphosis (mean deformity +19 degrees), the mean
      correction was 22 degrees. There was no statistically significant difference in
      subsidence between single- and multilevel corpectomy or between 360 degrees
      fusion and anterior fusion alone. The VAS scores improved by 35%, and the Nurick
      grade improved by 31%. The fusion rate was 100%. CONCLUSIONS: The preliminary
      results support the use of ECCs in the cervical spine in the treatment of
      patients with various disease processes. No significant subsidence was noted, and
      pain and functional scores improved in all cases. Expandable cylindrical cages
      appear to be well suited for cervical reconstruction and for correcting sagittal
      malalignment.

PMID- 16619675
TI  - Implantation of an empty carbon fiber cage or a tricortical iliac crest autograft
      after cervical discectomy for single-level disc herniation: a prospective
      comparative study.
AB  - OBJECT: The authors conducted a study to evaluate and compare prospectively the
      implantation of either an empty carbon fiber composite frame cage (CFCFC) or an
      iliac crest autograft after anterior cervical discectomy (ACD) for cervical disc
      herniation with monoradiculopathy. METHODS: Thirty-six consecutive patients with
      one-level radiculopathy due to single-level cervical disc herniation were treated
      by ACD, and implantation of either an empty CFCFC (24 patients) or an iliac crest
      autograft (12 patients). Radiological and clinical assessments were performed
      preoperatively, immediately postoperatively, and at 3, 6, and 12 months
      postoperatively. Fusion at the 12-month follow-up examination was demonstrated in
      96% of the patients in the cage group and in 100% of those in the autograft
      group. The mean anterior intervertebral body height was 3.7 mm preoperatively and
      3.9 mm at 12 months in the CFCFC, and 4.1 and 3.8 mm, respectively, in the
      autograft group. In cage-treated patients, neck pain, as measured using the
      visual analog scale (VAS) (Score 0 = minimum; 10 = maximum) decreased from 6.4
      preoperatively to 2.0 at 12 months, and radicular pain decreased from 8.4
      preoperatively to 1.5 at 12 months. In the autograft group, neck pain changed
      from a mean preoperative VAS score of 7.2 to 2.5 at 12 months, and radicular pain
      decreased from a preoperative mean of 7.8 to 1.4 at 12 months. Analysis of the 12
      Item Short Form Health Survey domains and the Oswestry Disability Index scores
      indicated a significant improvement in both the Physical and Mental Component
      Summary domains in both groups. CONCLUSIONS: Implantation of an empty CFCFC or a
      tricortical iliac crest autograft after ACD are safe and reliable options for the
      treatment of cervical disc herniation causing one-sided radiculopathy. Both
      procedures produced equally satisfying clinical and radiological results, leading
      to a high fusion rate and maintaining intervertebral height. Implantation of an
      empty CFCFC has the advantages of avoiding any donor site morbidity and requiring
      a significantly shorter operative time.

PMID- 16619676
TI  - Prevention of percutaneous electrode migration in spinal cord stimulation by a
      modification of the standard implantation technique.
AB  - OBJECT: Percutaneous spinal cord stimulation (SCS) electrodes are prone to
      migration even after scar tissue encapsulation. The authors devised a simple
      technique to eliminate longitudinal migration. METHODS: In 99 patients who
      received implanted percutaneous electrodes, less than 0.1 cm3 of silicone
      elastomer adhesive was injected between the anchoring sleeve and the electrode.
      As a result, no patient required revision surgery due to longitudinal electrode
      migration over a mean follow-up period of 20.2 +/- 12.3 months (range 1.8-39.7
      months). Postimplant SCS-related surgical procedures were required in 15 patients
      (15%) for the following indications: infection in three patients, expanded area
      of pain in four patients, lateral migration after the sutures eroded through the
      supraspinous ligament in one patient, postural changes in stimulation in one
      patient, receiver-site pain in two patients, technical failure in three patients,
      and inadequate pain relief in one patient. CONCLUSIONS: With modification of the
      standard technique for implantation of percutaneous SCS electrodes, no
      longitudinal migration of electrodes was noted in this series of 99 patients.

PMID- 16619677
TI  - Surgical complications of posterior lumbar interbody fusion with total
      facetectomy in 251 patients.
AB  - OBJECT: Previous studies of surgical complications associated with posterior
      lumbar interbody fusion (PLIF) are of limited value due to intrastudy variation
      in instrumentation and fusion techniques. The purpose of the present study was to
      examine rates of intraoperative and postoperative complications of PLIF using a
      large number of cases with uniform instrumentation and a uniform fusion
      technique. METHODS: The authors reviewed the hospital records of 251 patients who
      underwent PLIF for degenerative lumbar disorders between 1996 and 2002 and who
      could be followed for at least 2 years. Intraoperative, early postoperative, and
      late postoperative complications were investigated. Intraoperative complications
      occurred in 26 patients: dural tearing in 19 patients and pedicle screw
      malposition in seven patients. Intraoperative complications did not affect the
      postoperative clinical results. Early postoperative complications occurred in 19
      patients: brain infarction occurred in one, infection in one, and neurological
      complications in 17. Of the 17 patients with neurological complications, nine
      showed severe motor loss such as foot drop; the remaining eight patients showed
      slight motor loss or radicular pain alone, and their symptoms improved within 6
      weeks. Late postoperative complications occurred in 17 patients: hardware failure
      in three, nonunion in three, and adjacent-segment degeneration in 11.
      Postoperative progression of symptomatic adjacent-segment degeneration was
      defined as a condition that required additional surgery to treat neurological
      deterioration. CONCLUSIONS: The most serious complications of PLIF were
      postoperative severe neurological deficits and adjacent-segment degeneration.
      Prevention and management of such complications are necessary to attain good long
      term clinical results.

PMID- 16619678
TI  - Amelioration of spinal cord compressive injury by pharmacological preconditioning
      with erythropoietin and a nonerythropoietic erythropoietin derivative.
AB  - OBJECT: Spinal cord injury (SCI) is a devastating clinical syndrome for which no
      truly efficacious therapy has yet been identified. In preclinical studies,
      erythropoietin (EPO) and its nonerythropoietic derivatives asialoEPO and
      carbamylated EPO have markedly improved functional outcome when administered
      after compressive SCI. However, an optimum treatment paradigm is currently
      unknown. Because the uninjured spinal cord expresses a high density of EPO
      receptor (EPOR) in the basal state, signaling through these existing receptors in
      advance of injury (pharmacological preconditioning) might confer neuroprotection
      and therefore be potentially useful in situations of anticipated damage. METHODS:
      The authors compared asialoEPO, a molecule that binds to the EPOR with high
      affinity but with a brief serum half-life (t1/2 < 2 minutes), to EPO to determine
      whether a single dose (10 microg/kg of body weight) administered by intravenous
      injection 24 hours before 1 minute of spinal cord compression provides benefit as
      determined by a 6-week assessment of neurological outcome and by
      histopathological analysis. Rats pretreated with asialoEPO or EPO and then
      subjected to a compressive injury exhibited improved motor function over 42 days,
      compared with animals treated with saline solution. However, pretreatment
      efficacy was substantially poorer than efficacy of treatment initiated at the
      time of injury. Serum samples drawn immediately before compression confirmed that
      no detectable asialoEPO remained within the systemic circulation. Western blot
      and immunohistochemical analyses performed using uninjured spinal cord 24 hours
      after a dose of asialoEPO exhibited a marked increase in glial fibrillary acidic
      protein, suggesting a glial response to EPO administration. CONCLUSIONS: These
      results demonstrate that EPO and its analog do not need to be present at the time
      of injury to provide tissue protection and that tissue protection is markedly
      effective when either agent is administered immediately after injury.
      Furthermore, the findings suggest that asialoEPO is a useful reagent with which
      to study the dynamics of EPO-mediated neuroprotection. In addition, the findings
      support the concept of using a nonerythropoietic EPO derivative to provide tissue
      protection without activating the undesirable effects of EPO.

PMID- 16619679
TI  - The intracranial entrance of the atlantal segment of the vertebral artery in
      crania with occipitalization of the atlas.
AB  - OBJECT: An anomalous vertebral artery (VA) position can jeopardize an otherwise
      successful procedure, such as a posterior cranial fossa decompression for
      hindbrain herniation, and may increase the propensity for VA occlusion. METHODS:
      The authors describe the detailed anatomy of the entrance site of the VA in adult
      human crania in which there is occipitalization of the atlas. They found that if
      the atlantal posterior arch or hemiarch was fused to the occiput one should
      anticipate encountering an anomalous osseous pathway as the VA enters into the
      cranium, as evidenced by this finding in 80% of their specimens. An anomalous
      entry pathway was present in all but one left-sided specimen in which the left
      posterior hemiarch was not fused to the occiput and one right-sided specimen in
      which there was an unfused and rudimentary posterior arch of the atlas.
      CONCLUSIONS: The clinician should consider the possibility that the VA takes
      anomalous routes into the skull in cases in which there is occipitalization of
      the atlas.

PMID- 16619680
TI  - Evaluation of registration techniques for spinal image guidance.
AB  - OBJECT: Paired point matching alone and paired point matching combined with
      surface matching are the two techniques used for the registration step in
      preoperative computerized tomography-based spinal image guidance. In the present
      study the authors sought to compare paired point-matching registration alone with
      paired point matching supplemented with surface matching to determine if the
      addition of surface matching improves navigational accuracy. METHODS: Pedicle
      screws were placed in three embalmed human cervicothoracic spinal specimens
      during image guidance to serve as a reference points. The specimens were then
      rescanned, and each level was registered using paired point matching alone and
      then by paired point supplemented with surface matching. Navigational accuracy
      was assessed by placing the stereotactic probe in the center of the screw head,
      and measuring the apparent distance between the screw head and probe on the
      computer monitor. Statistical analysis was used to compare the registration error
      and navigational error between the two techniques. Seventy-five screws were
      placed at 46 vertebral levels. The mean registration error for the paired point
      matching/surface matching technique (0.5 mm) was significantly lower (p < 0.001)
      than that of the paired point matching alone technique (1.2 mm); however, the
      intertechnique difference in navigational error was nearly equivalent (1.3 mm
      compared with 1.4 mm) and statistically insignificant (p > 0.05). CONCLUSIONS:
      Although the addition of surface matching to paired point registration
      significantly decreased the mean registration error, the actual navigational
      accuracy between the two techniques was equivalent when easily distinguishable
      points were meticulously selected. The use of paired point matching alone did not
      compromise the accuracy of navigation and is likely to result in decreased
      operating time.

PMID- 16619681
TI  - The role of mitomycin C in reducing recurrence of epidural fibrosis after
      repeated operation in a laminectomy model in rats.
AB  - OBJECT: Extensive peridural fibrosis after lumbar spine surgery may contribute to
      poor outcome and recurrent symptoms leading to repeated operation. Secondary
      procedures are considerably hampered by the presence of scar tissue. Moreover,
      after excision of the peridural scar, the fibrous tissue may recur, leading to
      unsuccessful surgical outcome. Mitomycin C (MMC), an alkylating antibiotic
      substance isolated from Streptomyces caespitosus, potentially suppresses
      fibroblast proliferation after surgical intervention. The authors investigated
      the effect of MMC on the reformation of epidural fibrosis in a laminectomy model
      in rats. METHODS: Twenty-four Wistar rats underwent a repeated lumbar laminectomy
      3 months after the first operation. In 12 rats, MMC in a concentration of 1 mg/ml
      was locally applied to the laminectomy site. No treatment was performed in the
      control group of the other 12 rats. All rats underwent clinical evaluation.
      Mobility ratings and any evidence of neurological deficit were recorded. Twelve
      weeks after the second operation, the animals were killed for histological
      examination. The extent of epidural fibrosis and dural adherence was evaluated.
      All MMC-treated animals showed reduced epidural scarring, compared with the
      control group. In nine MMC-treated rats (75%), dural adhesions were moderate. In
      contrast, all control sites showed dense epidural fibrosis with marked dural
      adherence. No side effects of the treatment were observed. CONCLUSIONS: In this
      experimental study, MMC in a concentration of 1 mg/ml locally applied
      significantly reduced recurrence of epidural fibrosis and dural adhesions without
      any side effects after repeated spinal surgery in a laminectomy model in rats.

PMID- 16619682
TI  - Unilateral atlantal lateral mass hypertrophy. Report of four cases.
AB  - The authors report the cases of four patients in whom they diagnosed an extremely
      rare and hitherto unreported clinical condition-unilateral hypertrophy of the C-1
      lateral mass causing symptomatic cord compression. All patients presented with
      long-standing torticollis and progressive myelopathy. Three patients underwent
      posterior decompressive surgery and one underwent resection of the part of the
      lateral mass invading into the spinal canal and subsequent atlantoaxial plate and
      screw fixation. Clinical improvement of varying degrees occurred in all cases
      following surgery. The clinical recovery, however, was most remarkable in the
      patient who underwent resection of the bone portion indenting the cord. The
      follow-up periods ranged from 2 to 14 years. The remarkable similarity in the
      presenting clinical and radiological/neuroimaging features in all four patients
      suggests that unilateral hypertrophy of the lateral mass of atlas may be a
      defined clinical entity. The treatment strategy needs to be evaluated; however,
      resection of the compression-causing portion of the hypertrophic bone appears to
      be the best treatment option.

PMID- 16619683
TI  - Aggressive postoperative lumbar fibromatosis after the placement of
      instrumentation for treatment of spondylolisthesis. Case report.
AB  - This 50-year-old woman presented with a paravertebral lumbar fibromatosis
      (desmoid tumor) after undergoing the placement of instrumentation for lumbar
      spondylolisthesis. The tumor developed just cranial to the previous skin
      incision. Fibromatoses, or desmoid tumors, are uncommon infiltrative lesions that
      affect musculoaponeurotic structures, most often of the trunk and limbs. They are
      known to occur in association with surgery-related scars or implants and only
      rare examples appear in the neurosurgical and spine-related literature. In cases
      involving well-defined tumors in which radical resection is possible, surgery is
      the treatment of choice; however, the recurrence rate is high. The patient in the
      present case was followed for 14 months postoperatively and did not undergo
      radiotherapy; there was no recurrence. Although rare, this distinctive tumor
      should be considered in the differential diagnosis of postoperative paravertebral
      bulgings after neurosurgical and spinal operations.

PMID- 16619684
TI  - Microendoscopic partial resection of the sacral ala to relieve extraforaminal
      entrapment of the L-5 spinal nerve at the lumbosacral tunnel. Technical note.
AB  - The authors report the cases of three patients with L-5 radiculopathy caused by
      extraforaminal entrapment of the L-5 spinal nerve at the lumbosacral tunnel; this
      structure comprises the lumbosacral ligament, the sacral ala, and the L-5 and S-1
      vertebral bodies. All three patients suffered severe leg pain and neurological
      deficits compatible with L-5 radiculopathy. Decompressive surgery involved the
      microendoscopic partial resection of the sacral ala along the L-5 spinal nerve.
      All patients experienced immediate pain relief postoperatively. Microendoscopic
      partial resection of the sacral ala is an effective and minimally invasive
      surgical option for patients with extraforaminal entrapment of the L-5 spinal
      nerve.

PMID- 16619685
TI  - Lateral spinal artery aneurysm associated with a posterior inferior cerebellar
      artery main trunk occlusion. Case illustration.

PMID- 16619686
TI  - Intracranial hypotension.

PMID- 16619687
TI  - Spinal decompression.

PMID- 16619688
TI  - Burkitt's lymphoma and emerging therapeutic strategies for EBV and AIDS
      associated lymphoproliferative diseases in East Africa.

PMID- 16619689
TI  - Clinical characteristics of Burkitt's lymphoma from three regions in Kenya.
AB  - OBJECTIVES: To describe the clinical characteristics of Burkitt's lymphoma (BL)
      from three regions in Kenya at different altitudes with a view towards
      understanding the contribution of local environmental factors. DESIGN:
      Prospective cross-sectional study. SETTING: Kenyatta National Hospital and seven
      provincial hospitals in Kenya. METHOD: Histologically proven cases of Burkitt's
      lymphoma in patients less than 16 years of age were clinically examined and
      investigated. MAIN OUTCOME MEASURES: For every case the following parameters were
      documented: chief complaint(s); physical examination, specifically pallor,
      jaundice, oedema, lymphadenopathy, presence of masses, splenomegaly and
      hepatomegaly. Reports of evaluation of chest radiograph, abdominal
      ultrasound/scan, bone marrow aspiration, cerebral spinal fluid cytology, liver
      and kidney function tests, urinalysis, stool occult blood and full blood count
      results. Stage of disease was assigned A, B, C or D. Cases of BL from three
      provinces of Kenya with diverse geographical features were analysed: Central,
      Coast, and Western. RESULTS: This study documented 471 BL cases distributed as
      follows: Central 61 (males 39 and 22 females), M:F ratio 1.8:1; Coast 169 (111
      males and 58 females), M:F ratio 1.9:1; and Western 241 (140 males and 101
      females), M:F ratio 1.4:1. The major presenting complaints were: abdominal
      swelling--Central 36%, Coast 4% and Western 26%; swelling on the face--Central
      31%, Coast 81% and Western 64%; and proptosis--Central 3%, Coast 1% and Western
      9%. The mean duration of these complaints in weeks were Central 6.9, Coast 6.08,
      and Western 5.05. The initial physical finding was a tumour mass in 39%, 72% and
      54% of cases for Central, Coast and Western respectively. Tumour stage at
      diagnosis was: stage A--Central 21%, Coast 43% and Western 34%; stage B--Central
      10%, Coast 5% and Western 10%; stage C--Central 41%, Coast 34% and Western 30%;
      and stage D--Central 28%, Coast 17% and Western 26%. For the age and sex matched
      cases the results show that commonly involved sites were: abdomen--Central 35%,
      Coast 9% and Western 14%; jaw (mandible)--Central 24%, Coast 22% and Western 31%;
      maxilla--Central 6%, Coast 24% and Western 11%; and lymph nodes--Central 10%,
      Coast 4% and Western 8%. The disease stage was A--Central 33%, Coast 44% and
      Western 36%; stage B--Central 11%, Coast 10% and Western 27%; stage C--Central
      39%, Coast 34% and Western 27%; and stage D--Central 21%, Coast 13% and Western
      37%. CONCLUSION: This study shows that clinical features of childhood BL vary
      with geographical region. The variations are documented in proportion of jaw,
      maxilla, abdominal and lymph nodal sites involvement. The differences observed
      are potentially due to the local environmental factors within these provinces. BL
      cases from Western province had features, intermediate between endemic and
      sporadic. Coastal province BL cases were similar to endemic BL, while BL cases
      from Central province resembled more or less sporadic BL subtypes. Strategies to
      explain and investigate the local environmental factors associated with the
      observed differences may certainly contribute towards improved understanding and
      clinical management of BL.

PMID- 16619690
TI  - Oral combination chemotherapy in the treatment of AIDS-associated Hodgkin's
      disease.
AB  - OBJECTIVES: To determine the effectiveness of an oral combination chemotherapy
      regimen administered to patients with AIDS-associated Hodgkin's disease. DESIGN:
      Prospective, pilot phase II clinical trial. SETTING: Consecutive patient
      recruitment occurred at two medical centers in the United States: Albany Medical
      Center, Albany, New York, where patients were recruited prior to December 31,
      1996 (pre-HAART era); and University Hospitals of Cleveland, Cleveland, Ohio,
      where patients were recruited after January 1, 1997 (HAART era). INTERVENTION:
      Oral chemotherapy consisted of lomustine (100 mg/m2 day I for cycle one and odd
      cycles thereafter); etoposide (200 mg/m2 days 1 through 3); and cyclophosphamide
      and procarbazine (each 100 mg/m2 days 22 through 31). Cycles were repeated every
      six weeks. Colony-stimulating factor support (G-CSF in all instances) was
      allowed. MAIN OUTCOME MEASURES: Clinical demographic variables, peripheral blood
      counts, serum chemistries, CD4 lymphocyte count, histopathological subtype of
      Hodgkin's disease were identified for all patients, who were staged according to
      Ann Arbor criteria. DATA ANALYSIS: Common Toxicity Criteria were utilized to
      assess safety; response was assessed using ECOG criteria; and survival was
      analyzed by Kaplan-Meier methods and difference of survival between pre-HAART and
      HARART era was compared using log-rank test. RESULTS: Eleven patients (six in pre
      HAART era), all but one male, with a median age of 36 years, excellent
      performance status and advanced International Prognostic Score were treated.
      Myelosuppression was the major side effect and there were minimal other grade 3
      or greater toxicity all of which were promptly reversible. An overall objective
      response rate of 82% (with 18% complete responses) and median survival duration
      of 24 months (range 2.5 +/- 68) were observed. Survival was markedly improved in
      patients treated in the HAART era (median not reached versus 7.25 months, p =
      0.034). CONCLUSIONS: This feasibility study demonstrates acceptable tolerance and
      excellent clinical activity of oral combination chemotherapy in patients with
      AIDS-associated Hodgkin's disease. Improved survival is observed in combination
      with HAART therapy. Dose-modification of this regimen would be suitable to
      evaluate in the resource constrained setting and larger confirmatory studies are
      encouraged.

PMID- 16619691
TI  - Zidovudine: a targeted therapy for endemic Burkitt's lymphoma.
AB  - BACKGROUND: Although cyclophosphamide based regimens can produce remission rates
      approaching 60 to 80% in endemic Burkitts lymphoma, relapses and refractory
      disease are fairly common in developing countries, due to advanced stage disease
      and cost-constraints in the implementation of optimal chemotherapeutic protocols.
      OBJECTIVE: To evaluate an affordable, tolerable and targeted approach to
      chemotherapy for endemic Burkitt's lymphoma as would be desirable in resource
      poor settings such as Africa. METHOD: We present data and review pertinent
      literature that indicates that the antiviral agent Zidovudine specifically
      targets this tumour through a unique and novel mechanism. DATA SOURCE: Our
      original studies, publications original and review articles searched in Pubmed
      indexed for Medline. DATA EXTRACTION: A systematic review to identify studies
      relating to Zidovudine, EBV+ and Burkitt's lymphoma, indicating antiviral agents
      zidovudine targeting BL in a unique and novel mechanisms. DATA SYNTHESIS: Our
      data and a qualitative assessment of the relevant literature was undertaken,
      given the heterogenicity of the study types making it inappropriate to pool
      results across studies. CONCLUSION: Our data suggests that the incorporation of
      Zidovudine into Burkitt's regimens may enhance tumour kill and abbreviate the
      duration of treatment necessary for this disease. Furthermore, the addition of
      the widely available and inexpensive agent hydroxyurea, markedly potentiates the
      tumorcidal activity of Zidovudine in Epstein Barr virus positive Burkitt's
      lymphomas. We recommend that further clinical studies in patients afflicted with
      this disease are needed to clearly define this potential use of Zidovudine.

PMID- 16619692
TI  - Strategies to overcome myelotoxic therapy for the treatment of Burkitt's and AIDS
      related non-Hodgkin's lymphoma.
AB  - BACKGROUND: Strategies to circumvent or lessen the myelotoxicity associated with
      combination chemotherapy may improve the overall outcome of the management of
      patients particularly in resource poor settings. OBJECTIVES: To develop effective
      non-myelotoxic therapies for Burkitt's Lymphoma (BL) and AIDS-related non
      Hodgkin's lymphoma. DATA SOURCES: Publications, original and review articles,
      conference abstracts searched mainly on Pubmed indexed for medline. DATA
      EXTRACTION: A systematic review of the clinical problem of combination
      chemotherapy. Identification of clinical strategies that circumvent or lessen the
      myelotoxicity of combination cytotoxic chemotherapy. Length of survival, lack of
      clinically significant (> grade 3) myelosuppression and weight loss were used as
      markers of myelotoxicity. DATA SYNTHESIS: Review of published experience with
      some of these strategies including dose-modification of multi-agent chemotherapy;
      rationale for targeted therapies, and the preclinical development of a mouse
      model exploring the role of metronomic scheduling substantiate pragmatism and
      feasibility of these approaches. CONCLUSION: Myelotoxic death rates using multi
      agent induction chemotherapy approach 25% for endemic Burkitt's lymphoma and
      range between 20% to 60% for AIDS-related malignancy. This is mostly explained by
      the paucity of supportive care compounded by wasting and inanition attributable
      to advanced cancer and HIV infection making patients more susceptible to
      myelosuppressive side effects of cytotoxic chemotherapy. Investigations and
      alternative approaches that lessen or circumvent myelotoxicity of traditional
      cytotoxic chemotherapy for the management of Burkitt's lymphoma and AIDS-related
      non-Hodgkin's lymphoma in the resource-constrained setting are warranted.
      Pertinent pre-clinical and clinical data are emerging to support the need for
      abrograting the myelosuppressive effects of traditional cytotoxic chemotherapy.
      This can be achieved by developing targeted anti-viral and other strategies, such
      as the use of bryostatin 1 and vincristine, and by developing a preclinical mouse
      model to frame the clinical rationale for a pilot trial of metronomic therapy for
      the treatment of Burkitt's and AIDS-related lymphoma. Implementation of these
      investigational approaches must be encouraged as viable anti-cancer therapeutic
      strategies particularly in the resource-constrained settings.

PMID- 16619693
TI  - Mesenteric liposarcoma or lipodystrophy: an elusive diagnosis.
AB  - Mass lesions of the mesentery may be fortuitously encountered on computerized
      tomographic (CT) scans, posing a diagnostic challenge. Despite CT, magnetic
      resonance (MR) imaging and a surgical biopsy, a patient with mesenteric
      lipodystrophy was misdiagnosed as having a low-grade mesenteric liposarcoma.
      Spontaneous regression of the mass on control CT scan and review of the
      pathological material prompted us to reconsider the diagnosis of malignancy.
      Because a wide variety of tumors and pseudotumors produce alterations in the
      density and volume of mesenteric fat on CT scan, a surgical biopsy is usually
      necessary to obtain a tissue-specific diagnosis, but even then pathological
      findings may be equivocal. As final resort the natural evolution assessed by
      radiological follow-up can be of help in determining the nature of the disease.

PMID- 16619694
TI  - MR imaging of nodular fasciitis arising in the Hoffa fat pad.
AB  - Nodular fasciitis is a benign proliferative fibroblastic tumor arising most often
      in subcutaneous tissues or deep fascial planes. The lesion is under-reported in
      radiological literature. There are only a few reports on MR Imaging of nodular
      fasciitis. Location in the Hoffa fat pad is not described in the literature. We
      will present the case of a patient with nodular fasciitis in this area. The MR
      features will be discussed.

PMID- 16619695
TI  - Primary pancreatic and renal non-Hodgkin's lymphoma: CT and MR findings.
AB  - Primary malignant non-Hodgkin's lymphoma of the pancreas or the kidney is
      uncommon. We describe a case of primary non-Hodgkin's lymphoma of the pancreas
      consisting of 3 masses and causing acute pancreatitis, combined with a primary
      non-Hodgkin's lymphoma of the left kidney, without the presence of abdominal
      lymphadenopathies. Our case report is documented with CT as well as MR images.

PMID- 16619696
TI  - Colitis cystica profunda.
AB  - A 39-year-old woman with inflammatory bowel disease was admitted to the hospital
      because of cramping abdominal pain and diarrhea. Ultrasound of the abdomen
      revealed thickening of the wall of the descending colon. At endoscopy mucosa
      covered nodules with substenosis were seen. A double-contrast examination showed
      narrowing in the transition zone between the descending colon and sigmoid with
      mucosal nodularities and barium spots in between. Examination of the resection
      specimen revealed colitis cystica profunda. After surgical treatment the history
      of the patient was uneventful.

PMID- 16619697
TI  - Arthrographic and CT arthrographic findings in dorsal peripheral detachment of
      the triangular fibrocartilaginous complex.
AB  - Arthrography and CT arthrogram were evaluated in the diagnosis of dorsal
      peripheral detachment of the triangular fibrocartilaginous complex (TFCC) in the
      wrist. The imaging findings and medical records of 19 patients, who underwent
      surgical repair of a dorsal peripheral detachment of the TFCC, were
      retrospectively studied. Diagnoses were based on the results of the arthrography
      and CT arthrogram as well as on the clinical examination. The arthrographic
      features assessed included abnormal filling of the tendon sheath of the extensor
      carpi ulnaris (ECU) and irregular contrast extravasate in the dorsal ulnar and
      peristyloid region. The findings on arthrography and CT arthrography were
      correlated with the arthroscopic results. In conclusion, the arthrographic signs
      seem to be reliable findings in the diagnosis of dorsal detachment of the TFCC.

PMID- 16619698
TI  - Imaging of musculoskeletal soft tissue infection.
AB  - The role of different imaging techniques in the assessment of musculoskeletal
      soft tissue infection will be reviewed in this article. As classification
      according to the causative agent is impossible with imaging, soft tissue
      infections will be classified in view of their location. Consecutively,
      musculoskeletal soft tissue infections of the joints, tendons and bursae,
      muscles, the skin and its related structures as well as infectious lymphadenitis
      and lymphangitis will be discussed.

PMID- 16619699
TI  - Early oesophageal cancer demonstrated by double-contrast barium oesophagography.

PMID- 16619700
TI  - Pancreatic duct rupture in a 26-year-old patient.

PMID- 16619701
TI  - Cine-viewing of overlapping thin collimation images: an improved diagnostic tool
      in multislice helical CT of the bowel.
AB  - As compared to single slice helical CT, multislice helical CT does not only
      improve the quality of the individual images (in terms of slice sensitivity
      profile and image artifacts) and the range of scan coverage, it also enforces the
      CT postprocessing possibilities. The advantage of post-processing thin
      collimation bowel CT images with overlap and cine-viewing or paging is reported.
      The case report illustrates that cine-viewing of overlapping thin collimation
      images obtained with multislice helical CT, allows an excellent evaluation of the
      bowel loops resulting in the diagnosis of a perforated sigmoid carcinoma and its
      complications.

PMID- 16619702
TI  - Helicobacter pylori eradication in peptic dyspepsia.

PMID- 16619703
TI  - Drug susceptibility pattern of Helicobacter pylori in patients with dyspepsia at
      the Kenyatta National Hospital, Nairobi.
AB  - OBJECTIVE: To determine drug susceptibility pattern of Helicobacter pylori to
      metronidazole, clarithromycin, amoxicillin and tetracycline in patients
      presenting with dyspepsia at the Kenyatta National Hospital. DESIGN: Cross
      sectional descriptive study. SETTING: Kenyatta National Hospital, Nairobi.
      SUBJECTS: Two hundred and sixty-seven patients aged 15 to 85 years, presenting
      with dyspepsia and referred for upper gastro-intestinal endoscopy were recruited
      into the study. RESULTS: Between October 2003 and April 2004, 138 male and 129
      female patients aged 15-85 years, with a mean age of 45.4 years were studied.
      Gastritis was the most common endoscopic finding, occurring in 55%, followed by
      normal-looking mucosa in 27% and peptic ulcer disease in 16% of the patients. The
      rapid urease test was positive in 184 patients (69%). The culture yield was 62%
      of these CLO (Campylobacter like organisms) positive biopsies. The MIC90 (minimum
      inhibitory concentration) was 256 mg/l for metronidazole, 1.5 mg/l for
      clarithromycin, 1.5 mg/l for tetracycline and 0.75 mg/l for amoxicillin. The MIC
      values for amoxicillin were significantly higher in the female patients (p =
      0.02) but showed no significant variation for age. The MIC values for
      metronidazole, tetracycline and clarithromycin showed no significant difference
      for age or gender. MIC values for tetracycline were significantly higher for
      patients with duodenitis and duodenal ulcer p = 0.009 and 0.02, respectively.
      CONCLUSION: All isolated H. pylori organisms were resistant to metronidazole. The
      susceptibility of the H. pylori isolates was 93.6% for clarithromycin, 95.4% for
      amoxicillin and 98.1% for tetracycline. The MIC90 for amoxicillin and
      clarithromycin were found to be close to the upper limit of the susceptibility
      range. There was a rising MIC90 for tetracycline and metronidazole compared to
      that found in a previous study in 1991.

PMID- 16619704
TI  - Tuberculosis and oral Candida species surveillance in HIV infected individuals in
      Northern Kenya, and the implications on tuberculin skin test screening for DOPT
      P.
AB  - OBJECTIVE: To determine the pattern of opportunistic infections such as TB and
      Candida species in HIV infected patients in Northern Kenya. DESIGN: Cross
      sectional study. SETTING: Five health facilities in Moyale (n=224), Mandera
      (n=121) and Turkana Kakuma; (n=83), Lopiding; (n=94) districts during different
      periods in 2003. SUBJECTS: Five hundred and fifty two patients. RESULTS: In total
      94 (18%) patients were found to be HIV positive (Moyale=42, Mandera=13, Turkana;
      Kakuma=8, Lopiding=31). Only 65 of 94 HIV positive patients provided saliva
      samples. Of these, 11 (17%) were TB smear positive and 19 (29.2%) were colonized
      by oral Candida species. The Candida isolates were as follows; Co-infection of
      Candida species and TB (n=4), C. albicans only (n=12), C. tropicalis only (n=1),
      C. albicans and C. glabarata (n=1) and C. albicans, C. glabarata and C.
      tropicalis. co-infection (n=1). CONCLUSION: The findings provides an important
      insight into the differences in mucosal susceptibility to bacteria (TB) infection
      and fungal (Candida species) colonization during HIV immunosuppression, based on
      collected blood, sputum and saliva specimens. Further studies are needed to
      elucidate the comparative transmission dynamics and pathogenetic mechanisms of
      these opportunistic infections-in different regions of Kenya. Such studies would
      improve the efficiency of directly observed preventive therapy programme (DOPT-P)
      whose implementation involves screening by tuberculin skin testing.

PMID- 16619705
TI  - Characterisation of a heparan sulfate proteoglycan homologue OvPG-1 from
      Onchocerca volvulus.
AB  - OBJECTIVE: To determine the role of an immunodominant antigen OvPG-1 in human
      onchocerciasis. DESIGN: Cross-sectional study of subjects living in three
      onchocerciasis endemic areas. SETTING: Mbonge and Tubah divisions of Western
      Cameroon and in Esmeralda Province of Ecuador. SUBJECTS: There were 94 and 99
      subjects from the Cameroon rain forest and savannah respectively, and 83 endemic
      residents from Ecuador. RESULTS: The IgG2 anti-OvPG-1 responses of visually
      impaired and microfiladermic patients were significantly higher than for their
      age and sex matched counterparts with normal vision and no microfiladermia
      (p=0.024). Furthermore, the isotype specificity of anti-OvPG-I responses varied
      for the various onchocerciasis endemic zones. IgG1, IgG2, IgG3 and IgE levels
      correlated with the presence of microfilariae in Cameroon, but not in Ecuador.
      CONCLUSION: Increased IgG and IgE levels to the antigen OvPG-1 seem to correlate
      with the development of onchocercal eye pathology. The present results suggest
      that the OvPG1 is a dominant antigen of Onchocerca volvulus with a significant
      role in the pathogenesis of onchocerciasis.

PMID- 16619706
TI  - Risk factors for child under-nutrition with a human rights edge in rural villages
      of North Wollo, Ethiopia.
AB  - OBJECTIVE: To identify the factors associated with childhood under-nutrition in
      North Wollo, Ethiopia. DESIGN: A cross-sectional study. SETTING: Four
      purposefully selected rural villages (kebeles) in North Wollo zone of the Amhara
      Region, Ethiopia. SUBJECTS: One hundred-forty four sampled households with under
      five year old children (n=200) comprising of 96 male-headed, 24 female-headed and
      24 landless with children aged between six and 59 months. MAIN OUTCOME MEASURES:
      Determinations of anthropometric measurements and various socio-economic factors.
      RESULTS: The overall prevalence rate of under nutrition as determined by
      stunting, underweight and wasting was 44.5%, 25.0% and 9.0% respectively with
      more preponderance among the toddlers. The proportion of under nutrition was
      higher in female-headed households. Shortage of farmland, lack of irrigation,
      dispossession of livestock, shortage of non-farm employment options, parental
      illiteracy, high number of children, water inadequacy, food taboos and wrong
      eating habits of families, poor child feeding practices, deprivation of health
      nutrition education as well as maternal attributes such as young motherhood, low
      body mass index and short stature of mothers influenced the nutritional status of
      the children. The prominent risk factors for undernutrition among children were
      dispossession of livestock, child food taboos and wrong eating habits of
      families, deprivation of health/nutrition education, short stature and early
      marriage of mothers. CONCLUSION: This study led to the conclusion that
      improvement of household resources through promotion of irrigation and initiation
      of income generating livelihood options can reverse the nutrition situation for
      better. Health and nutrition education focusing on appropriate child feeding,
      eradication of harmful traditional practices such as early marriage and
      inequitable intra-household food distribution, encouragement of family planning
      and nutrition interventions including food diversification is recommended.

PMID- 16619707
TI  - Perceptions and practices of vaginal birth after Caesarean section among
      privately practicing obstetricians in Kenya.
AB  - OBJECTIVE: To determine perceptions, preferences and practices of vaginal birth
      after Caesarean. DESIGN: Cross-sectional descriptive study. SETTING: Private
      clinics of obstetricians in five major towns of Kenya. SUBJECTS: Obstetricians in
      private practice. MAIN OUTCOME MEASURES: Practice and experiences in trial of
      labour (TOL); need for, and application of, selection criteria in TOL;
      perceptions on outcomes of TOL and patient preference; perception on trends of
      vaginal birth after Caesarean (VBAC) and need for policy on TOL. RESULTS: Nearly
      all respondents (98.4%) believed in the need for, and application of, selection
      criteria for allowing TOL. However, only 23% believed in routine screening with
      radiological pelvimetry, while 63.2% believed in routine foetal weight
      estimation. All obstetricians (100%) have ever managed TOL in private practice,
      and 74% had managed at least one case in the last six months. Despite lack of
      tangible selection criteria, 83.1% think that most women prefer TOL while 95.1%
      discourage it if perceived as inappropriate. Failure rate of TOL was perceived to
      be more than 50% by 35.2% of the respondents. A majority of the respondents
      (about 75%) would prefer TOL on themselves or their spouses. Those who perceived
      that there was a falling trend of VBAC were 58%, citing increased demand by
      mothers (45.7%), obstetricians' convenience (40.0%) and fear of litigation
      (26.8%) as the reasons for this observation. A fluid policy of "TOL whenever it
      is deemed as appropriate" was preferred by 88.7%. CONCLUSION: The perception of
      obstetricians is that desire for VBAC predominates over elective repeat
      Caesarean. However, consensus on appropriate selection criteria is lacking, which
      leaves the obstetrician in a management dilemma. Hence, there is need to study
      outcomes of both ERC and TOL in order to come out with objective policy
      guidelines on management of one previous Caesarean in pregnancy.

PMID- 16619709
TI  - The sub-pubic angle in adult indigenous Malawian subjects.
AB  - BACKGROUND: A number of parameters are used to assess the pelvis for clinical,
      physical and forensic anthropological reasons. When it is adequately assessed
      within any population group, the pelvis displays wide variations. Although the
      sub-pubic angle is one of the three forensically important angles of the pelvic
      outlet, literature is scanty or lacking on East and Central Africans, and no
      published report is available on indigenous Malawian subjects. OBJECTIVES: To
      determine the sub-pubic angle in indigenous Malawians and compare them with
      angles from other population groups previously reported. DESIGN: A cross
      sectional study. SETTING: Queen Elizabeth Central and Blantyre Adventist
      hospitals in the city of Blantyre. SUBJECTS: One hundred and nineteen antero
      posterior radiographs of pelves of adults indegenous Malawians aged 20-84 years
      to determine their sub-pubic angle. RESULTS: Women showed significantly wider sub
      pubic angles than men (129.07 +/- 14.190 SD women and 99.16 +/- 15.730 SD men; P
      < 0.001), confirming similar results previously studied in other population
      groups. We have demonstrated that the sub-pubic angle alone could accurately
      assign sex to 67.12% of males and 63.04% of females, and race could be accurately
      assigned to 21.92% of men and 89.96% of females. Malawians showed significantly
      wider angles than Amerindians, Black and White Americans (P < 0.001). CONCLUSION:
      This study documents sexual and racial differences and for the first time (on
      comparison) the sub-pubic angles indicate geographical variations, underpinning
      the need to establish normal ranges of these angles in any given population. We
      recommend the establishment of local references of the sub-pubic angle to other
      countries in the sub-region.

PMID- 16619708
TI  - Vitamin and mineral intake of twelve adolescent male Kalenjin runners in western
      Kenya.
AB  - OBJECTIVE: To determine whether the diet of adolescent male Kalenjin runners in a
      boarding school setting was adequate compared to FAO/WHO recommendations. DESIGN:
      A cross-sectional design study. SETTING: Marakwet High School in western Kenya.
      SUBJECTS: A study of twelve adolescent male Kalenjin runners was carried out to
      determine their micronutrient intake. MAIN OUTCOME MEASURES: Over a two-week
      period, samples of the main eaten food were collected for analysis of
      micronutrient distribution and a daily 24 recall interview performed to determine
      additional food intake. RESULTS: The estimated intakes were compared to
      recommended or suggested adequate daily intake (RSDI) by FAO/WHO. For vitamin A,
      pyridoxine, folic acid, vitamin B12, vitamin C, and vitamin E, the intakes
      represented only 17%, 82%, 56%, 55%, 95%, and 65% of RSDI, respectively. In
      contrast, the intakes of thiamine. riboflavin, and niacin all met RSDI by 208%,
      107%, and 131%, respectively. Similarly, the intakes of magnesium, iron, and zinc
      were 272%, 404%, and 122% of RSDI, respectively, while calcium and selenium were
      below, 47% and 49%, respectively. The daily intakes of phosphorous, copper, and
      chromium were estimated to 4214 mg, 1309 microg, and 79 microg, respectively.
      CONCLUSION: Total daily micronutrient intake of the twelve Kalenjin runners was
      far from adequate compared to FAO/WHO daily recommended and suggested adequate
      intake.

PMID- 16619710
TI  - Pattern of clefts of the lip and palate managed over a three year period at a
      Nairobi hospital in Kenya.
AB  - BACKGROUND: The pattern of cleft lip and palate in the African population remains
      uncertain. The few studies of clefts in African populations have suggested that
      the pattern of these defects may be significantly different from those reported
      in other population groups. However, most of these studies have been based on
      very small sample sizes bringing into question the validity of those findings.
      OBJECTIVE: To analyse the pattern of cleft lip and palate cases managed at a
      Nairobi hospital. DESIGN: A retrospective descriptive study. SETTING: Gertrude's
      Garden Children's Hospital, a private exclusive children's hospital in Nairobi,
      where cleft lip and palate treatment was being offered at subsidised rates to
      needy children under the sponsorship of an international organization. SUBJECTS:
      Three hundred and nine cases were seen during the study period. RESULTS: Age at
      presentation ranged between 1 week and 45 years, with 75% presenting between 0-5
      years. The average age was 10 months. Gestation histories were missing for most
      cases but for those with gestation histories none were significant. Most children
      ranked between first to third birth orders, suggesting birth to young mothers.
      Six cases of associated deformities were identified among the cases. No syndromic
      clefts were seen. The most common cleft deformity was the cleft lip and palate
      (CL+P) followed by isolated cleft lip (CL). Isolated cleft palate was least
      common. There was a male preponderance in all cleft types and most of the clefts
      occurred on the left side. CONCLUSION: The pattern of clefts in this study does
      not differ significantly from those reported in the literature for the non
      African populations.

PMID- 16619711
TI  - Presenting chief complaints and clinical characteristics among patients attending
      the Department of Paediatric Dentistry Clinic at the University of Nairobi Dental
      Hospital.
AB  - OBJECTIVES: To evaluate the chief complaints and clinical presentation among
      patients attending the Department of Paediatric Dentistry clinic at the
      University of Nairobi Dental Hospital (UONDH). DESIGN: A retrospective survey of
      hospital records. SETTING: The University of Nairobi Dental Hospital. SUBJECTS:
      Patients who attended the Department of Paediatric Dentistry clinic during a
      three year period. MAIN OUTCOME MEASURES: Chief complaint, dental caries,
      gingivitis, traumatic injuries, treatment at first visit. RESULTS: The records of
      800 patients were examined, including 391 male and 400 female. The average age of
      the patients was 9.0 years. The presenting complaint for most patients was dental
      pain (31.5%), orthodontic related complaints (25.4%) and dental decay (19.7%).
      Very few children attended for dental check-up (3.9%). Five hundred ninety
      (73.8%) children suffered from dental caries, while 275 (34.4%) children
      manifested gingivitis. The average number of teeth decay was 3.71 (SD+/-3.76).
      Only 51 (6.4%) children attended with traumatic injuries to the dentition.
      Treatment performed at the first visit mainly consisted of dental extractions
      (21.8%), oral prophylaxis and dental health education (20.5%) and restorative
      treatment (20.0%). CONCLUSIONS: The presenting complaint for most patients was
      pain. However, there was an almost equal demand for orthodontic treatment. Dental
      caries was the most prevalent dental disease. Oral prophylaxis and dental health
      education (DHE) constituted a significant component of treatment offered at first
      visit.

PMID- 16619712
TI  - Vasculitis in HIV: report of eight cases.
AB  - OBJECTIVE: To describe vasculitis in HIV patients, their CD4 levels, anatomical
      sites affected and clinical patterns. DESIGN: Prospective, descriptive study.
      SETTING: Kisumu District Hospital and Nairobi Rheumatology Clinic between January
      2002 and May 2005. SUBJECTS: Eight patients with HIV and vasculitis. RESULTS:
      Eight patients (four males and four females) were recruited with an age range of
      24-61 years, mean 33.13 years. Five had central nervous system vasculitis and
      three had peripheral vasculitis. The CD4 counts were low, range 2-200 cells/mm3
      (mean of 79.25 cells/mm3), normal levels of CD4 are 355-1298 cells/mm3,
      indicating severe immunosuppression. Two patients tested positive for HBV
      (hepatitis B virus). CONCLUSION: HIV associated vasculitis is recognised and may
      be complicated by coinfection with hepatitis viruses. It occurs at low CD4
      counts. Central nervous system involvement is a common site. Management is
      multidisciplinary.

PMID- 16619713
TI  - Post-infarction ventricular septal defect in Nairobi: case report.
AB  - Post infarction ventricular septal defect results from perforation of the
      ventricular septum secondary to ischaemic injury following myocardial infarction.
      Ischaemic heart disease till recently was thought to be an uncommon disease in
      this part of the world, but now more and more cases are being seen as a result of
      the changes in thelife styles of the population in this country and in the
      developing world in general. This is a case report of the first case of post
      infarction ventricular septal defect presenting to surgery for repair in this
      country.

PMID- 16619714
TI  - P.G. Jani--"acute colonic pseudo obstruction (Ogilvie's syndrome): case report".

PMID- 16619715
TI  - Air pollution and health.

PMID- 16619716
TI  - Serum lead levels in civil servicemen and public transport drivers in Makkah
      City, Saudi Arabia.
AB  - BACKGROUND: The risk of exposure to lead varies significantly with source and
      exposure rates. Short-term exposure to high levels of lead can cause clinical
      symptoms starting from vomiting and ending with coma, even death. OBJECTIVE: To
      describe the prevalence of occupational exposure with lead (Pb) health hazard in
      Makkah Al-Mukarramah city. DESIGN: Comparative study with geographical locations.
      SETTING: The city of Makkah, Saudi Arabia. SUBJECTS: Eighty nine servicemen and
      sixty nine public transport drivers in the city of Makkah, Saudi Arabia were
      analysed by atomic absorption spectrophotometer. RESULTS: Twelve per cent of
      those sampled showed serum levels higher than 40 ug/dl while the mean values were
      23.14 and 15.2 ug/dl in public transport drivers and civil servicemen
      respectively. CONCLUSION: Accumulation and dispersion rates rather than exposure
      time appear to be the determinant factors for serum Pb levels. Clinical history
      did not correlate with serum-Pb levels, except in two cases of public transport
      drivers.

PMID- 16619718
TI  - Psychiatric morbidity among leprosy patients in Teso and Busia districts of
      Western Kenya.
AB  - OBJECTIVE: To establish the magnitude of psychiatric disorders among leprosy
      patients in western Kenya. DESIGN: A cross-sectional descriptive study. SETTING:
      Busia and Teso districts in western Kenya. SUBJECTS: A sample of 152 male and
      female, adult leprosy patients. RESULTS: The prevalence of psychiatric morbidity
      (PM) was 53.29%. The PM was positively correlated with physical disability and
      marital status but not with age, sex, education, type of leprosy, or duration of
      the illness. The prevalence of psychiatric morbidity was lower among Kenyan
      leprosy patients compared to studies carried out in India (56% to 78%). It was
      high compared to the rate of psychiatric morbidity in those seeking medical help
      in primary health care centres in Kenya, which was recently estimated to be 10%.
      CONCLUSION: The prevalence of PM in leprosy patients in western Kenya was lower
      than that in studies carried out in India. This could be attributed to de
      institutionalisation and re-integration of leprosy sufferers back into their
      local communities. Since the rate was more than double that in the general Kenyan
      population and seemed to be related to presence of physical disability, an
      appraisal of psychiatric services offered to these patients is needed.

PMID- 16619717
TI  - Predictors of mortality in HIV-1 exposed uninfected post-neonatal infants at the
      Kenyatta National Hospital, Nairobi.
AB  - OBJECTIVES: To identify potential predictors of mortality, to determine mortality
      rate and to identify prevalent causes of death in a cohort of HIV-1 exposed
      uninfected infants. DESIGN: Prospective cohort study. SETTING: Kenyatta National
      Hospital, Nairobi, Kenya. SUBJECTS: Three hundred and fifty one HIV-1 exposed
      uninfected post-neonatal infants who survived to one year of age. RESULTS:
      Sixteen infants died (post-neonatal mortality rate of 47/1000 live births), 14
      (88%) before six months of age. The most frequently identified medical conditions
      at death included bronchopneumonia, diarrhoea and failure to thrive. In
      multivariate analysis, prematurity (RR=10.5, 95%CI 3.8-29.1, p<0.001), teenage
      motherhood (RR=3.6, Cl 1.0-13.2, p=0.05) and symptomatic maternal HIV-1 disease
      (RR=2.7, CI 0.9-7.7, p=0.06) were associated with infant mortality. CONCLUSION:
      Prematurity, teenage motherhood and symptomatic HIV-1 maternal disease were
      important predictors for post-neonatal mortality in this cohort of HIV-1 exposed
      uninfected infants. These factors should be considered in monitoring and follow
      up in prevention of mother-to-child HIV-1 transmission (PMTCT) programs.

PMID- 16619719
TI  - Diagnosis of fallopian tube patency.
AB  - OBJECTIVES: To evaluate and compare the diagnostic value of hysterosalpingography
      (HSG) and laparoscopic chromopertubation (LCP), in the diagnosis of fallopian
      tube patency. DESIGN: A comparative prospective study. SETTING: The infertility
      clinic of the Department of Obstetrics and Gynaecology, Ga-Rankuwa hospital
      (Medical University of Southern Africa), Pretoria, South Africa. SUBJECTS: Fifty
      patients were initially diagnosed with either unilateral or bilateral tubal block
      using HSG. Six to eight weeks later the same women were subjected to LCP to
      assess tubal patency. MAIN OUTCOME MEASURES: Diagnostic accuracy of HSG to
      establish tubal patency, site of occlusion and the presence of other pathologies
      was compared with results obtained after laparoscopic chromopertubation (LCP).
      RESULTS: Hysterosalpingography diagnosed bilateral proximal, bilateral distal and
      mixed (i.e. one side proximal and the other distal) tubal occlusion in 15(40.5%);
      13(35.1%) and five (13.5%) cases respectively. Diagnostic laparoscopy confirmed
      the above sites of occlusion in nine (24.3%), 71(45.9%) and three (8.1%) cases.
      Laparoscopy detected bilateral tubal patience in three (8.1%) patients, in whom
      HSG had diagnosed tubal occlusion. USG was able to detect peritubal Adhesion in
      only four (10.8%) patients as compared with 11 patients when LCP procedure was
      used. In comparison with HCP, hysterosalpingography demonstrated 70% specificity
      for accurately diagnosing proximal tubal occlusion. CONCLUSION: On a comparative
      scale, HSG demonstrated reduced positive predictive value especially for
      bilateral proximal tubal occlusion. However, in spite of its relatively limited
      value for accurately identifying tubal patency, HSG should still serve as a
      useful primary investigation.

PMID- 16619720
TI  - Dystonia: case series of twenty two patients.
AB  - OBJECTIVE: Dystonia is a rare neurological disorder characterised by sustained
      muscle contraction with resultant bizarre muscle movements and hence bizarre
      posturing. The pathophysiology is not well understood but it is believed there is
      dysfunction of the cortico-striatal-thalamo-cortical circuitry and projections.
      There is very scanty literature in sub-Saharan Africa. DESIGN: Retrospective
      descriptive case series. SETTING: Outpatient clinics of the authors, the Nairobi
      Hospital and the Mater Hospital, Nairobi, Kenya. SUBJECTS: A cohort of twenty two
      consecutive patients of indigenous Kenyan origin, seen by the authors between
      1996 and January 2005 were described. This study was carried out to describe
      characteristics of 22 patients. RESULTS: Males comprised of 15 (68.2%) of the
      cases. Late onset dystonia was found in 12 (54.5%) cases. Over half of the
      patients had focal dystonia and only 13.6% had generalized dystonia, all of whom
      were of early onset variety. There was significant delay in diagnosis of dystonia
      with 68.2% of patients being diagnosed after 12 months of onset of symptoms.
      CONCLUSION: Dystonia is rare; however, multi-centre studies are required to map
      out prevalence rates of the disease in the country. There is need to highlight
      the presentation of the disease amongst clinicians and patients as this would
      improve diagnosis rate, early intervention and appropriate management. Genetic
      studies need to be done.

PMID- 16619722
TI  - Laparoscopic cholecystectomy at the Nairobi Hospital: a personal experience with
      42 cases.
AB  - BACKGROUND: Laparoscopic cholecystectomy is a recent entry in the treatment of
      gall bladder disease in Kenya and is slowly gaining acceptance. Like all new
      techniques, it has generated considerable controversy and debate on its merits
      over the traditional open operation. OBJECTIVE: To report a personal series of
      laparoscopic cholescystectomy operations, to determine the safety, effectiveness
      and acceptability of the method in a private hospital setting in Kenya and in
      general if this surgery should be promoted in this country. DESIGN: Retrospective
      case study of personal series of laparoscopic cholecystectomy over a period of
      two years. SETTING: The Nairobi Hospital. RESULTS: Forty two patients underwent
      the operation, five males and 37 females. There were three conversions to open
      cholecystectomy for various reasons, but the rest did well and results were
      favourable. CONCLUSIONS: Although initial capital investment in laparoscopic
      equipment is high and although there is a learning curve for surgeons which
      discourages some, the method offers advantages which cannot be ignored. It is
      safe and gives patients great satisfaction. There is less pain than in the
      traditional open method, and patients have a shorter hospital stay and early
      return to work. Where facilities permit it should be practiced; future effort
      should be directed at making it safer and more widely accepted by training users.

PMID- 16619721
TI  - Immunoglobulin G bound to ovine placenta is eluted by surgical cannulation and
      acid perfusion in situ.
AB  - OBJECTIVE: To elute placental bound immunoglobulin G (IgG) in situ. DESIGN:
      Laboratory based experimentation. SETTING: Biological Sciences Department, The
      University of Newcastle Australia and the Department of Biochemistry, University
      of Nairobi, Kenya. SUBJECTS: Twelve pregnant ewes 10 to 15 days before the onset
      of natural parturition. RESULTS: Placental eluates were rich in IgG, and IgG2.
      The relative molecular weight of placental IgG was estimated at 158kDa by gel
      filtration chromatography. Analysis of eluate by SDS PAGE revealed the heavy and
      light chains of IgG at 57 and 27kDa respectively together giving a relative
      molecular weight of 168kDa. CONCLUSION: Placental bound IgG may be crucial in
      immunology of pregnancy and together with the cognate antigen thereof may be
      useful as models for the study of maternal-fetal interaction in human pregnancy
      and in the development of experimental immunotherapy to immunologically
      compromised pregnancies in humans and livestock.

PMID- 16619724
TI  - Bladder perforation and development of a vesico--vaginal fistula following
      laparoscopic assisted vaginal hysterectomy: case report.
AB  - Bladder injury with subsequent development of a Vesico-Vaginal Fistula following
      a Laparoscopic Assisted Vaginal Hysterectomy is reported. The injury was not
      recognised intra--operatively or in the immediate post-operative period. On the
      third post-operative day, the patient complained of abdominal distention, and a
      reduced urine output was noted. There was no haematuria. Conservative management
      by continuous bladder drainage was not successful. A low-pressure cystogram done
      on day eight revealed a bladder leakage. On day 21, a repeat low-pressure
      cystogram showed a vesico-vaginal fistula. A successful transvesical repair by
      laparotomy was undertaken on day 23. The possible mechanisms of injury,
      prevention and the principles of management are discussed.

PMID- 16619723
TI  - Influenza: the next pandemic?: A review.
AB  - OBJECTIVES: To examine existing information on the recent influenza outbreaks in
      order to create awareness of a possible influenza pandemic and to suggest future
      research areas in developing control strategies in Kenya. DATA SOURCES: Review of
      literature via Internet, articles, journals and un-refereed features from the
      media and personal communications. DATA SELECTION: Most published data from 1979
      to March 2005 found to reveal cases of influenza outbreaks were included in the
      review. Also, selected articles on the recent outbreaks and professional guidance
      on influenza infections were critically examined and analyzed. DATA EXTRACTION:
      Abstracts and articles identified were accessed, read to establish relevance to
      this review. DATA SYNTHESIS: Important points were prioritised and then included
      as subtitles; below each subtitle, published works were included. Finally, a
      table of influenza outbreaks and the strains of the viruses involved were drawn
      as summary. CONCLUSION: Influenza is a highly contagious, acute respiratory
      disease that may spread rapidly and pervasively through a population. Due to the
      diversity of susceptible reservoirs of influenza viruses and the interspecies
      transmission recently reported, a mutated strain of the virus to which people
      have no immunity could cause an influenza pandemic once the virus gains efficient
      and sustained human-to-human transmission. The fear that avian influenza could be
      a precursor to the next pandemic is real and inevitable, given the extremely high
      case-fatality ratio among confirmed cases and that genetic sequencing of
      influenza A (H5N1) viruses from human cases in Thailand and Vietnam show
      resistance to the antiviral medication amantadine and rimantadine. This calls for
      a high level of preparedness to avoid a public health emergency. Nowhere is this
      paradigm more real than in Africa.

PMID- 16619725
TI  - Acute ileus following ventriculoperitoneal shunt: case report.
AB  - A three month old girl with progressive hydrocephalus from birth had a
      ventriculoperitoneal (VP) shunt, during which the cerebrospinal fluid (CSF) was
      found to be xanthochromic. She developed acute ileus four hours post-operatively
      and continued to deteriorate. The shunt was exteriorised as an external
      ventricular drain. She did well and another VP shunt was inserted later. Acute
      ileus following VP shunt is not common, but can occur in the presence of
      xanthochromic CSF. It is advisable that when such CSF is encountered during VP
      shunt, the initial management should be external ventricular drainage, followed
      later by VP shunt when the CSF becomes clear. This can be life saving.

PMID- 16619726
TI  - Electrocardiographic screening in unmedicated vagrant psychotics on
      rehabilitation.

PMID- 16619727
TI  - Diabetes care in Kenya--where are we and which way forward?

PMID- 16619728
TI  - Risk factor profile and the occurrence of microvascular complications in short
      term type 2 diabetes mellitus at Kenyatta National Hospital, Nairobi.
AB  - BACKGROUND: Type 2 diabetes has a long pre-clinical period before diagnosis,
      during which there may be development of complications, both of microvascular and
      macrovascular types. OBJECTIVE: To determine the risk factor profile of
      hyperglycaemia, hypertension and dyslipidaemia in patients with short-term (=/ <
      2 years) type 2 diabetes. DESIGN: Cross-sectional descriptive study over six
      months. SETTING: Outpatient diabetic clinic of Kenyatta National Hospital.
      SUBJECTS: Ambulatory patients with type 2 diabetes. RESULTS: One hundred patients
      were included. The mean (SD) duration of diabetes was 10.3 (7.5) months. There
      were 66% of the study subjects with obesity, 50% with hypertension, 29% had ideal
      glucose control and less than 40% had high LDL-cholesterol. Twenty eight (28%)
      who had polyneuropathy had significant differences in their older age, higher
      total and LDL-cholesterol compared with those who did not have polyneuropathy.
      Twenty five (25%) of the study patients had micro-albuminuria and only 1% had
      macro-albuminuria. There were no significant differences in the selected
      characteristics between study patients with and those without albuminuria. Only
      7% of the study patients had retinopathy on direct ophthalmoscopy. CONCLUSION:
      Microvascular complications occurred in patients with type 2 diabetes of short
      duration of not more than two years. The risk factors of hypertension, poor
      glycaemic control, dyslipidaemia and cigarette smoking were present in a fair
      proportion of the study patients. Patients with type 2 diabetes should be
      actively screened for complications and the risk factors thereof, even if the
      diabetes was of recent onset.

PMID- 16619729
TI  - Lipid profile of ambulatory patients with type 2 diabetes mellitus at Kenyatta
      National Hospital, Nairobi.
AB  - BACKGROUND: Patients with type 2 diabetes are at high of cardiovascular events
      because they have abnormal lipid status compared to their non-diabetic
      counterparts. OBJECTIVE: To determine the quantitative lipid profile of
      ambulatory patients with type 2 diabetes mellitus. DESIGN: Prospective, cross
      sectional descriptive study. SETTING: Out-patient diabetic clinic of the Kenyatta
      National Hospital. SUBJECTS: Ambulatory patients with type 2 diabetes but without
      obvious cardiovascular, renal or foot complications. RESULTS: A total of 213
      patients with type 2 diabetes were studied, 56.8% were females. The age range of
      the study population was 34 to 86 years, mean(sd) age of females was 54.45 (9.4)
      years and that of males was 55.83 (9.3) years. The mean body mass index (BMI) of
      females was 27.85 (6.2) kg/m2 and 25.98 (5.8) kg/m2 for males. The female
      subjects were more obese than the males in this study. Over 70% of the study
      participants had total cholesterol > 4.2 mmol/l, 43.8% and 57.6% of the females
      and males respectively had LDL-C > 2.6 mmol/l , 25.6% of the females and 30% of
      the males had HDL-C < 1.00 mmol/l. Only a modest proportion of males (28.3%) and
      females (32.2%) had triglycerides > 1.7 mmol/l. The LDL-C showed a significant
      positive correlation with age, duration of diabetes, fasting blood glucose, and
      total cholesterol but no correlation with glycated haemoglobin, body mass index,
      gender and the mode of glucose-lowering treatment. CONCLUSION: There was
      significant proportion of quantitative dyslipidaemia in the study population
      especially with the Total--and LDL- cholesterols. Although treatment goals and
      lipid thresholds for cardiovascular risk in diabetes are not yet well-defined,
      even by the large randomized trials, high-risk patients with significant
      quantitative dyslipidaemia would require deliberate effort to correct the
      abnormal values to reduce the risk status. These high-risk patients without
      complications but already had significant dyslipidaemia, which enhances the risk
      of cardiovascular events, certainly required therapeutic intervention.

PMID- 16619730
TI  - Patterns of homocysteine in Kenyans with type 2 diabetes without overt
      cardiovascular disease at Kenyatta National Hospital, Nairobi.
AB  - BACKGROUND: Increased total homocysteine (tHcy) is an independent risk factor for
      cardiovascular disease. The measurement of tHcy in blood is therefore of
      potential great importance especially in patients with type 2 diabetes.
      OBJECTIVE: To determine the total homocysteine levels in ambulatory patients with
      type 2 diabetes. DESIGN: Cross-sectional, prospective study. SETTING: Outpatient
      diabetic clinic of the Kenyatta National Hospital. SUBJECTS: Ambulatory patients
      with Type 2 diabetes without overt cardiovascular, renal, liver or other chronic
      disease. MAIN OUTCOME MEASURES: Serum levels of tHcy, HbA1c, lipids and socio
      demographic characteristics. RESULTS: A total of 115 patients, 48% males, with
      type 2 diabetes were included in the study. The mean (sd) age of the males was
      56.85 (8.96) years and of the females was 55.68 (8.93) years. The mean (sd) total
      serum homocysteine for males of 12.97 (6.06) micromol/l was significantly higher
      than that of the females of 10.64 (4.41) micromol/l. The cholesterol, glycated
      haemoglobin, the body mass index and blood pressure of the study subjects did not
      show any statistically significant influence on their homocysteine levels.
      However, increasing age and duration of diabetes showed a significant linear
      relationship with rising level of total serum homocysteine. Some study
      participants reported smoking habit but unreliably. CONCLUSION: There was a
      significant proportion of the study patients with high levels of serum
      homocysteine, although most of them were of low to intermediate risk category. It
      may be prudent to assay homocysteine levels in patients with type 2 diabetes who
      are either older or have had diabetes for long duration for potential
      intervention.

PMID- 16619731
TI  - Cardiovascular risk factors in patients with type 2 diabetes mellitus in Kenya:
      levels of control attained at the Outpatient Diabetic Clinic of Kenyatta National
      Hospital, Nairobi.
AB  - OBJECTIVES: To determine the proportion of specific cardiovascular risk factors
      in ambulatory patients with type 2 diabetes and the levels of control achieved in
      them. DESIGN: Prospective, cross-sectional study over a six month period.
      SETTING: Out-patient diabetic clinic of the Kenyatta National Hospital. SUBJECTS:
      Two hundred and eleven patients with type 2 diabetes. MAIN OUTCOME MEASURES:
      Sociodemographic attributes, duration of diabetes, levels of glycaemia, body
      weight, blood pressure, fasting lipids and modes of treatment. RESULTS: A total
      of 211 patients were enrolled, 57.3% were females. The mean (SD) age for women
      was 54.45 (9.44) and that of men was 55.8 (9.02) years. About 77% of the study
      population were on oral glucose-lowering agents with or without insulin but less
      than 30% achieved HbA1c < 7%; 15% were active cigarette smokers; about 50% were
      hypertensive with female predominance but 65% of them did not achieve desired
      blood pressure level inspite of treatment. Just over 50% had raised LDL
      cholesterol and over 75% had raised total cholesterol but only three men were on
      statins without achieving desired targets. Body mass index above 30 kg/m2 as a
      measure obesity was found in 32% of females and 16% males. Most of the study
      patients admitted use of Aspirin at certain times in the course of their
      diabetes. CONCLUSION: The study showed that specific cardiovascular risk factors
      of hyperglycaemia, dyslipidaemia, hypertension and obesity were prevalent
      although not adequately controlled to targets. Statin use was extremely low in
      people who already needed them. Regular Aspirin use was infrequent because many
      patients did not quite understand its role in their diabetes treatment. It is
      recommended that a more pro-active approach in multifactorial address of
      cardiovascular risk factors be used in high-risk patients with type 2 diabetes to
      forestall future cardiovascular events.

PMID- 16619732
TI  - Diabetic ketoacidosis: clinical presentation and precipitating factors at
      Kenyatta National Hospital, Nairobi.
AB  - OBJECTIVE: To determine the clinico-laboratory features and precipitating factors
      of diabetic ketoacidosis (DKA) at Kenyatta National Hospital (KNH). DESIGN:
      Prospective cross-sectional study. SETTING: Inpatient medical and surgical wards
      of KNH. SUBJECTS: Adult patients aged 12 years and above with known or previously
      unknown diabetes hospitalised with a diagnosis of diabetic ketoacidosis. RESULTS:
      Over a nine month period, 48 patients had DKA out of 648 diabetic patients
      hospitalised within the period, one died before full evaluation. Mean (SD) age
      was 37 (18.12) years for males, 29.9 (14.3) for females, range of 12 to 77 years.
      Half of the patients were newly diagnosed. More than 90% had HbA1c > 8%, only
      three patients had HbA1c of 7-8.0%. More than 90% had altered level of
      consciousness, with almost quarter in coma, 36% had systolic hypotension, almost
      75% had moderate to severe dehydration. Blunted level of consciousness was
      significantly associated with severe dehydration and metabolic acidosis. Over 65%
      patients had leucocytosis but most (55%) of them did not have overt infection.
      Amongst the precipitating factors, 34% had missed insulin, 23.4% had overt
      infection and only 6.4% had both infection and missed insulin injections.
      Infection sites included respiratory, genito-urinary and septicaemia. Almost
      thirty (29.8%) percent of the study subjects died within 48 hours of
      hospitalisation. CONCLUSION: Diabetic ketoacidosis occurred in about 8% of the
      hospitalised diabetic patients. It was a major cause of morbidity and mortality.
      The main precipitant factors of DKA were infections and missed insulin
      injections. These factors are preventable in order to improve outcomes in the
      diabetic patients who complicate to DKA.

PMID- 16619733
TI  - Diabetic ketoacidosis: risk factors, mechanisms and management strategies in sub
      Saharan Africa: a review.
AB  - BACKGROUND: Diabetic ketoacidosis is the most common hyperglycaemic emergency in
      patients with diabetes mellitus, especially type 1 diabetes. It carries very high
      mortality in sub-Saharan Africa, both in the treated patients and those who are
      presenting to hospital with diabetes for the first time. OBJECTIVE: To review the
      risk factors, mechanisms and management approaches in diabetes ketoacidosis in
      published literature and to discuss them in the context of why a significant
      proportion of patients who develop diabetic ketoacidosis in sub-Saharan Africa
      still have high mortality. DATA SOURCE: Literature review of relevant published
      literature from both Africa and the rest of the world. DATA SYNTHESIS: The main
      causes or precipitants of DKA in patients in SSA are newly diagnosed diabetes,
      missed insulin doses and infections. The major underlying mechanism is insulin
      deficiency. Treated patients miss insulin doses for various reasons, for example,
      inaccessibility occasioned by; unavailability and unaffordability of insulin,
      missed clinics, perceived ill-health and alternative therapies like herbs,
      prayers and rituals. Infections also occur quite often, but are not overt, like
      urinary tract, tuberculosis and pneumonia. Due to widespread poverty of
      individuals and nations alike, the healthcare systems are scarce and the few
      available centres are unable to adequately maintain a reliable system of insulin
      supply and exhaustively investigate their hospitalised patients. Consequently,
      there is little guarantee of successful outcomes. Poor people may also have sub
      optimal nutrition, caused or worsened by diabetes, more so, at first presentation
      to hospital. Intensive insulin therapy in such individuals mimics 're-feeding
      syndrome', an acute anabolic state whose outcome may be unfavourable during the
      period of treatment of diabetic ketoacidosis. CONCLUSIONS: Although mortality and
      morbidity from diabetic ketoacidosis remains high in sub-Saharan Africa, improved
      healthcare systems and reliable insulin supply can reverse the trend, at least,
      to a large extent. Individuals and populations need empowerment through
      education, nutrition and poverty eradication to improve self-care in health and
      living with diabetes.

PMID- 16619734
TI  - Focus on delay as a strategy for care designs and evaluation of diabetic foot
      ulcers in developing countries: a review.
AB  - BACKGROUND: While foot care services for diabetic patients are necessary if limb
      morbidity and wastage are to be reduced, they may not be sufficient. Even when
      the few service centers and personnel that are available appear to be functioning
      relatively well, patients still face multiple barriers to derive maximum benefits
      from the services. OBJECTIVES: To review certain aspects of care of diabetes foot
      ulcers in developing countries with emphasis on causes of delay in care delivery.
      DATA SOURCES: Review of published literature on care of diabetic foot ulcers as
      well as our local experiences. MAIN OUTCOME MEASURES: Levels of potential or
      actual delay in care delivery and causes of such delay in pre-hospital phase,
      access to hospital and within-hospital phase of care. DATA SYNTHESIS AND
      CONCLUSIONS: The barriers or causes of delay are observed to occur at various
      levels: decision to seek care, reaching the treatment facility and receiving the
      desired optimal care. The usual main causative/ risk factors that include
      peripheral neuropathy causes inattention and delays the decision to seek care;
      peripheral vascular insufficiency and infection are both involved in initiation
      of diabetic foot ulcers and are also major causes of delay in ulcer healing
      process. Aside from the processes unique to diabetes, the health care providers
      and the facilities of care have had major contributions in delaying the desired
      care of the foot ulcers. This may arise from heavy workload, priority illnesses,
      shortage of required supply for standard care and/or just wrong attitudes.
      Patients' inadequate knowledge of self-care, unique socio-economic and socio
      cultural characteristics are also contributors to the barriers that compound sub
      optimal foot care. Care programme designs that lay emphasis on causes of delay
      are more likely to seek to eliminate such causes. Just like justice, footcare
      delayed is foot (care) denied.

PMID- 16619735
TI  - The nutrition situation: an overview.
AB  - Malnutrition remains a major problem in both developing and industrialized
      countries and is getting worse in selected settings. However, progress has been
      made in alleviating malnutrition, and the motivation and tools for tackling
      malnutrition and its consequences have never been more favorable than they are
      now. Indeed, the genomic developments spawned by the ongoing biological
      revolution are increasing the pressure to solve problems that lead to low
      birthweight, stunting, disorders stemming from micronutrient deficiencies, and
      other manifestations of undernutrition.

PMID- 16619736
TI  - Priority nutritional concerns in Asia.
AB  - The sustained economic growth and increasing economic stability in the Asian
      region over the last three decades have been accompanied by changing lifestyles
      leading to significant changes in the food and nutrition issues facing Asian
      countries. The chronic diseases associated with excessive consumption of
      nutrients, especially fat, are becoming increasingly apparent. At the same time,
      Asia has a disproportionate share of the malnutrition problem. Underweight and
      stunting remain significant problems in many Asian communities, and micronutrient
      deficiencies of iron, iodine, and vitamin A continue to afflict large population
      groups. Effective data collection and analysis are essential to formulate and
      implement intervention programs to address both sides of the changing nutrition
      scenario in Asia.

PMID- 16619737
TI  - Food security in Latin America.
AB  - Although the nutrition situation in most Latin American countries is improving
      and malnutrition is easing, worrisome factors are emerging. Huge rural-to-urban
      migrations have been accompanied by a worsening nutrition situation in rural
      populations, especially in Mexico, Colombia, and Brazil, a phenomenon not readily
      apparent from average food availability and malnutrition data. Average figures
      can also mask the severe nutrition problems that persist in four densely
      populated areas: the Caribbean Islands, Central America, the Andean region, and
      parts of Brazil. Although globalization is improving the nutritional status of
      many population groups in Latin America, it is also creating new pressures. Latin
      American countries dependent on agriculture are especially vulnerable.

PMID- 16619738
TI  - Three criteria for establishing the usefulness of biotechnology for reducing
      micronutrient malnutrition.
AB  - The fundamental reason that plant breeding using either conventional breeding or
      biotechnology is so cost-effective is that the benefits of a one-time investment
      at a central research location can be multiplied over time across nations all
      over the world. Supplementation and fortification incur the same recurrent costs
      year after year in country after country. However, each intervention has its own
      comparative advantages, such that a combination of several interventions is
      required to substantially reduce micronutrient malnutrition. Improving the
      density of trace minerals in plants also reduces input requirements and raises
      crop yields. A simulation model for India and Bangladesh demonstrated that $42
      million invested in conventional breeding in developing and planting iron- and
      zinc-dense varieties of rice and wheat on only 10% of the acreage used for these
      crops would return $4.9 billion in improved nutrition (including a total of 44
      million prevented cases of anemia over 10 years) and higher agricultural
      productivity.

PMID- 16619739
TI  - The promise of biotechnology in addressing current nutritional problems in
      developing countries.
AB  - To meet the nutritional needs of a rapidly growing world population, which is
      likely to reach 8 billion by 2030, 50% more food grains with higher and more
      stable yields must be produced. Biofortification is considered the most effective
      way to increase micronutrient intakes. It is low cost and sustainable and does
      not require a change in eating habits or impose recurring costs. A research
      project to improve the iron and zinc content of rice was initiated at the
      International Rice Research Institute in 1992. Several experimental lines of rice
      with increased iron and zinc content have been produced. In another experiment
      rices with beta-carotene have been produced. Other experimental efforts aim at
      raising the micronutrient content in wheat, maize, cassava, sweet potatoes, and
      beans. Maize with improved amino acid balance is being grown in several African
      countries.

PMID- 16619740
TI  - Can biotechnology help meet the nutrition challenge in sub-Saharan Africa?
AB  - The successful efforts in the 1980s to redress nutrition problems in sub-Saharan
      Africa are being eroded. Countries in eastern and southern Africa are now facing
      serious food shortages because of recurrent droughts, floods, civil wars, and the
      concomitant growing poverty. The potential for biotechnology to alleviate hunger
      holds promise if the new technology can be adapted to the prevailing
      sociocultural context in Africa. Agronomists and biotechnologists need to work
      together to ensure that the biotechnology agenda for Africa is responsive to the
      food and nutrition needs of its people.

PMID- 16619741
TI  - Food biotechnology and nutrition in Africa: a case for Kenya.
AB  - Household food consumption surveys indicate that the diet in Kenya is ill
      balanced and that many families cannot afford nutrient-rich foods such as meat
      and fruits. In this regard, rural populations-the majority of the Kenyan
      population-are much worse off than urban populations. Agriculture, the most
      important sector in the Kenyan economy, contributes 27% of the gross domestic
      product and generates 65% of the country's export earnings. Food-enhancing
      biotechnologies thus could increase national food yields and fill nutrition gaps
      by contributing to household and national food security and poverty reduction in
      Kenya. To overcome barriers to adopting biotechnology to improve food crops in
      Kenya and elsewhere in Africa, policy makers must create a receptive environment
      for, increase public understanding of, and stimulate investment in the new
      technology.

PMID- 16619742
TI  - The potential for biotechnology to improve the nutritional value of cassava.
AB  - Cassava, a starch-rich plant that has poor protein content and usually poor
      vitamin content, feeds about 600 million people each day. When cereals can no
      longer be grown because of soil fertility problems, it is often still possible to
      grow cassava. It is the third most important source of dietary calories in the
      tropics, and reliance on the crop is especially high in West and Central Africa.
      The International Laboratory for Tropical Agricultural Biotechnology is promoting
      research to improve cassava productivity and is a leader in developing genetic
      engineering to improve the quantitative and qualitative traits of this essential
      food crop.

PMID- 16619743
TI  - Research and development of transgenic plants in Malaysia: an example from an
      Asian developing country.
AB  - In 2000, agriculture contributed 13% to the national gross domestic product of
      Malaysia. The country of 23 million people has created a competitive program
      coordinated by the Ministry of Science, Technology and the Environment, research
      institutions, and universities to undertake biotechnology research in several
      areas. Intensified research efforts are under way on oil palm, rubber, rice,
      papaya, and orchids. Although the most progress has been made in rice and papaya,
      no transgenic crop is ready for field trials. Nonetheless, preliminary steps have
      been taken to prepare for the trials, and detailed testing protocols are being
      developed.

PMID- 16619744
TI  - Opportunities for nutritionally enhanced maize and wheat varieties to combat
      protein and micronutrient malnutrition.
AB  - Naturally occurring variation detected in the germplasm of maize and wheat, two
      of the top three cereal crops in the world, provides options for incorporating
      higher levels of iron, zinc, and beta-carotene into these grains. In addition,
      quality protein maize (QPM) has been developed from naturally occurring
      variation; its seed contains enhanced levels of lysine and tryptophan, two
      essential amino acids lacking in cereals. The International Maize and Wheat
      Improvement Center, along with its many partners, has identified several maize
      and wheat varieties with 25% to 30% higher grain iron and zinc concentrations.
      Wild relatives of wheat have been found to contain some of the highest iron and
      zinc concentrations in the grains. Although these accessions are often low
      yielding and have poor grain quality, backcrossing to bread wheat could result in
      highly nutritious cultivars. Options are now available for conventional and
      biotechnology-assisted improvement of the nutritional content of maize and wheat
      germplasm.

PMID- 16619745
TI  - Biotechnology-derived nutritious foods for developing countries: needs,
      opportunities, and barriers: discussion summary.
AB  - Improvements in diet diversification and quality can be facilitated by greater
      cooperation between the agricultural and the nutrition communities, according to
      an expert panel that met in early 2002. Encouraged to think innovatively, the
      panelists agreed that modern technology offers the potential to increase the
      amount and nutritional content of the food supply in developing countries,
      especially if the enhancements are made to the highest-yielding indigenous staple
      crops and if a total food-systems approach is taken. All types of interventions
      should be evaluated for their cost-effectiveness in preventing nutritional
      deficiencies in the developing world and for their sustainability.

PMID- 16619746
TI  - Impact of fortification of flours with iron to reduce the prevalence of anemia
      and iron deficiency among schoolchildren in Caracas, Venezuela: a follow-up.
AB  - In Venezuela, a severe economic crisis starting in 1983 provoked a progressive
      reduction in the quantity and quality of food consumed by people from the low
      socioeconomic strata of the population. This situation resulted in a continuous
      increase in the prevalence of iron deficiency in the 1980s and 1990s. In 1993, an
      iron-fortification program was started, in which precooked corn and white wheat
      flours were enriched with iron, vitamin A, thiamine, niacin, and riboflavin.
      White wheat flour was enriched with the same nutrients, except for vitamin A. In
      1996 we published the results of the impact of fortification of precooked corn
      and white wheat flours on the prevalence of anemia and iron deficiency in the
      population. A survey carried out in Caracas in 307 children aged 7, 11, and 15
      years showed that the prevalence of iron deficiency measured by serum ferritin
      concentration dropped from 37% in 1992 to 16% in 1994, only one year after the
      iron-fortification program began. The prevalence of anemia, as measured by the
      hemoglobin concentration, diminished from 19% to 10% during the same period. This
      article reports the results of three other surveys carried out in 1997, 1998, and
      1999 on children of the same age and socioeconomic groups that were evaluated in
      1990, 1992, and 1994. There were no significant differences in anemia or iron
      deficiency among the last three surveys. The prevalence results from the last
      seven years seem to indicate that, after a dramatic reduction in 1994, iron
      deficiency tended to stabilize, while the prevalence of anemia increased to the
      same level found in 1992, before the fortification program started.

PMID- 16619747
TI  - Time trends in the intrafamily distribution of dietary energy in rural India.
AB  - The intrafamily distribution of dietary energy in 5,458 households from seven
      states in India was assessed from 24-hour dietary recall data collected by the
      National Nutrition Monitoring Bureau during 1996-97. The energy consumption,
      expressed as percentage of recommended dietary intake (%RDI), of preschool
      children, schoolchildren, and adolescents was compared with that of adult men and
      women in the same households. Time trends in the intrafamily distribution of
      dietary energy were assessed by comparing the data with those collected in 1975
      80 using the same procedures in the same villages. About one-third of the
      preschool children had an inadequate intake of energy, even when their adult
      counterparts had an adequate intake, whereas only about 7% of the preschoolers
      and their parents were consuming inadequate amounts of energy. The extent of
      energy inadequacy was much less in adolescents and school-age children than in
      preschool children. This was true even when the adults in the same households had
      an adequate energy intake. In 1996-97, there was a significant increase in the
      proportion of households with preschool children consuming inadequate energy,
      although both adult men and women were consuming energy-adequate diets as
      compared with the dietary data collected in the same villages in 1975-80. The
      results indicate the need to provide effective nutrition education for parents
      regarding the nutritional needs of their children.

PMID- 16619748
TI  - Standardized evaluation of iodine nutrition in West Africa: the African phase of
      the thyromobil program.
AB  - Extensive programs of iodine supplementation by iodated salt have been
      implemented in Africa during the last decade. The present work evaluated their
      effectiveness in Benin, Burkina Faso, Mali, and Togo. A van equipped with a
      sonographic device visited 39 sites in the four countries. The prevalence of
      goiter was evaluated on the basis of the determination of thyroid volume by
      ultrasonography in 4,011 randomly selected 6- to 12-year-old schoolchildren of
      both sexes in the 39 sites. The concentration of urinary iodine was measured in
      1,545 of these children. The iodine content of table salt collected at home by
      the children was measured by test kits in 3,202 salt samples, 415 of which were
      also analyzed by titration. Based on the results obtained by the kits, 83.7% to
      97.9% of the salt samples contained iodine. However, the test kits had a low
      sensitivity and specificity in comparison with titration. The median urinary
      iodine was within an acceptable range (100-300 14 g/L) in the four countries, but
      almost one-third of the values were still below normal. The prevalence of goiter
      was normal (< 5%) in Benin and Togo, and it was 22.4% and 13.4%, respectively, in
      Burkina Faso and Mali. These results indicate marked improvement of the status of
      iodine nutrition in comparison with the situation reported only a few years ago
      in the same countries, but quality control of the iodine content of salt and
      monitoring of the iodine status of the populations need to be improved.

PMID- 16619749
TI  - Relationship between waist circumference and blood pressure among the population
      in Baghdad, Iraq.
AB  - We studied the relationship between waist circumference and hypertension among
      the Iraqi population in Baghdad. The study was carried out during 1999-2000. Body
      weight, height, waist circumference, and blood pressure were measured. According
      to multivariate analyses that included control for age and body mass index, waist
      circumference for men was positively and significantly correlated with systolic
      and diastolic blood pressure (r = 0.31 for systolic pressure and r = 0.30 for
      diastolic pressure; p < .009). For women, the correlations were r=0.39 for
      systolic and r = 0.40 for diastolic pressure (p < .001). Intervention programs
      designed to reduce waist circumference may have significant public health
      significance in reducing the incidence of hypertension.

PMID- 16619750
TI  - Chronic poisoning by hydrogen cyanide in cassava and its prevention in Africa and
      Latin America.
AB  - Africa produces more than 30 million tons of cassava on about 5 million hectares
      (6 tons per hectare). Approximately 80% of the root production and 70% of the
      harvested area are from Western Africa. Recent reports suggest that the ingestion
      of poorly processed cassava roots is associated with the incidence of an ataxic
      neuropathy (konzo) in African countries. When cassava-based diets are not
      supplemented with good sources of protein and iodine, goiter and rickets are also
      prevalent. In certain countries of Africa where the rate of ataxic neuropathy is
      high, the incidence of thyroid disorders is also high. Persons consuming poorly
      processed cassava in large quantities are susceptible to neuropathologies caused
      by cyanide. Cyanide detoxification in the body is impaired by protein deficiency.
      When properly processed, the root of cassava is safe and cheap as a major dietary
      energy source for humans and domestic animals; however, a cassava-based diet will
      lack sufficient protein and will be particularly deficient for the growth and
      development of children unless it is supplemented by protein from animal,
      including fish, or legume sources. Cassava leaves, if they are appropriately
      cooked, can be a useful source of some nutrients.

PMID- 16619751
TI  - Participation in labor-intensive public works program (LIPWP): effect on staple
      crop production in southeastern Botswana.
AB  - A labor-intensive public works program (LIPWP) aims to improve the income of
      rural households. One of the common criticisms of the LIPWP is that it is a
      disincentive for staple crop production. This study, conducted between February
      and May 2000, examined the association between participation in an LIPWP and
      staple crop production in southeastern Botswana. Participant households were
      those with at least one member on a semipermanent LIPWP. A control group was
      drawn from households that were eligible to participate in the LIPWP. All
      participants in the LIPWP were included, while nonparticipant households were
      randomly selected. A structured questionnaire was administered to 160 control and
      153 participant households. The odds of having no staple crop in the control
      group were 1.8 times (95% CI, 0.98 to 3.54) higher than that of the LIPWP
      participants (p = .087), while the odds of having no staple crop in a household
      with a head between 45 and 64 years of age were 2.5 times (95% CI, 1.06 to 5.96)
      higher than that of a household with a head less than 45 years old (p < .037).
      Having more than 10 livestock equivalent units reduced the risk of having no
      harvest by 40% (95% CI, 0.29 to 1.12). The view that participation in the LIPWP
      results in reduced staple crop production does not seem to be supported by our
      data.

PMID- 16619752
TI  - Seasonal undernutrition in rural Ethiopia: magnitude, correlates, and functional
      significance.

PMID- 16619753
TI  - The Egyptian food subsidy system: structure, performance, and options for reform.

PMID- 16619754
TI  - LATINUT: a new forum on nutrition for Latin America.

PMID- 16619755
TI  - Iron Deficiency Program Advisory Service (IDPAS).

PMID- 16619757
TI  - A handful of hope.

PMID- 16619758
TI  - A challenge of proportion.

PMID- 16619756
TI  - Living larger.

PMID- 16619759
TI  - Well-seated.

PMID- 16619760
TI  - Strengthening the core.

PMID- 16619761
TI  - Choosing mobility.

PMID- 16619762
TI  - Laser therapy's evolution.

PMID- 16619763
TI  - Lasers: no longer science fiction.

PMID- 16619764
TI  - The stuff of dreams.

PMID- 16619765
TI  - The mother of invention.

PMID- 16619766
TI  - Surviving 2006 guidelines.

PMID- 16619767
TI  - Talking points for mercury.

PMID- 16619768
TI  - Study of ARNP protocols.

PMID- 16619769
TI  - Clinical exellence exemplar. Kimberly Doyon.

PMID- 16619770
TI  - Professional Liability Insurance 101.

PMID- 16619772
TI  - Chemtrina: direct hits, near misses, and opportunities for prevention.

PMID- 16619773
TI  - University of Pittsburgh Nursing Students learn disaster prepardness thru the
      "Three Cane Sisters--Hurricanes Katrina, Rita, and Wilma".

PMID- 16619774
TI  - Illinois nurses begin drive for ratios.

PMID- 16619775
TI  - Government by the people...not buy the politicians.

PMID- 16619776
TI  - 'Catastrophic' care.

PMID- 16619777
TI  - Which side are they on?

PMID- 16619778
TI  - A rising tide lifts all yachts.

PMID- 16619779
TI  - Who's in charge here? The short answer was: 'nobody'.

PMID- 16619780
TI  - Getting active to halt privatization.

PMID- 16619782
TI  - Top hospitals restructure ERs to improve performance.

PMID- 16619781
TI  - A history of social progress: health visitors.

PMID- 16619783
TI  - Central DuPage Hospital ranks in top 10% of hospitals for pioneering stroke
      treatment.
AB  - It wasn't long ago that patients suffering a stroke had little hope of recovering
      or even surviving after experiencing a bursting brain blood vessel or tiny clots
      in arteries that stop oxygen-rich blood flow, killing or damaging brain nerve
      cells. In 1996. one of the nation's top community hospitals started a
      comprehensive stroke program that today saves many lives.

PMID- 16619784
TI  - Hospitals respond to public disclosure of mortality, complications and prices.
AB  - When Florida became one of the first states in the nation to use a public website
      to disclose data on hospital mortalities, infections, complications and prices,
      some hospitals began to immediately plan or speed up performance improvement
      projects.

PMID- 16619785
TI  - New Orleans' doctors: still MIA.

PMID- 16619786
TI  - How safe is your patient data?

PMID- 16619787
TI  - Rx vs OTC? Damned if you do,...

PMID- 16619788
TI  - Secrets for a successful malpractice defense.

PMID- 16619789
TI  - A simple change.

PMID- 16619790
TI  - 10 ways to foil an embezzler.

PMID- 16619791
TI  - Refusing a difficult patient.

PMID- 16619792
TI  - [Study of transport properties of the polymeric membranous dressing with silver
      ions].
AB  - The transport properties of polymeric membraneous dresing silver ion containing
      Textus Bioactive were studied. This dressing is made of three types of
      theromoplastic polymeric fibers, formed into two-layers membrane. In first layer
      occure the polymeric fiber, which the core is hydrophobic and hydrophilic
      surfaces contain a silver zeolite. These fibers neighborours with hydrophilic
      super absorbing polymers. Third type of polymeric fibers occur in the second
      layer of membrane and is arranged parallel to surface's skin, creating a net
      preventing stick of membraneous dressing to treated wound. Using of the Kedem
      Katchalsky equations the transport model of this membrane and the temporal and
      concentration characteristics of transport parameters (hydraulic permeability,
      refection and solute permeability) were determined. Experimental results show
      that the polymeric membranous dressing contain the silver ions posses non-linear
      transport properties, which are consequence of structure and physicochemical
      properties of polymeric membranes.

PMID- 16619793
TI  - Mathematical model equation of the volume flows through polymeric membrane of
      heterogeneous non-ionic solutions.
AB  - Formalism leading to more general form of the Kedem-Katchalsky equation
      describing osmotic membrane transport, considering local unhomogenity of
      solutions called concentration boundary layers and influence of gravitational
      factor on membrane transport kinetics was presented. In order to test this
      formalism, osmotic volume flux was calculated, on the basis of experimental
      membrane transport parameters and aqueous glucose solutions in isothermal
      conditions. Obtained calculation's results are conformable to adequate
      experimental results presented in previous paper for flat polymeric membrane used
      in medicine (Biophys. Chem. 1986, 24, 173).

PMID- 16619794
TI  - [New method of derivation of practical Kedem-Katchalsky membrane transport
      equations].
AB  - In the paper original manier of derivation of practical transport Kedem
      Katchalsky equations (K-K) describing fluxes: volume of solute (Jv) and dissolved
      substance (Js) for nonelectrolyte, evoked by simultaneous action of direct
      oriented hydrostatic (deltap) and osmotic (deltaII) pressures of nonelectrolytic
      solutions was presented. Mathematic expressions describing oefficients
      characterizing permeability of the membrane: omegadeltaII and omegadeltap,
      manners of their derivationand their physical interpretation were presented.
      Equation describing coefficient LD was also derived. Suggested manier of
      derivation makes K-K equations easier to interpret.

PMID- 16619795
TI  - Polyoxyethylenated methyl esters of rape oil fatty acids as non-ionic surfactants
      in a model drug form with albendazole.
AB  - Systematic research has been conducted on the applying of Rofams (oxyethylathed
      rape oil methyl esters) as solubilizing agents of albendazole. Homologous series
      of Rofams containing average amount of oxyethylene units (nTE) ranging between 20
      to 60 was used for investigation. An attempt has been made to apply investigated
      surface active agents as an auxiliary in production of model tablets with
      albendazole. Basic morphological parameters of granulates (bulk density, tapped
      density, Carr index, angle of repose) were determined. The dissolution testing
      procedure, friability and standard deviation from an average tablet mass were
      conducted to evaluate properties of produced tablets. The solubility of
      albendazole increases in the presence of Rofams in the aqueous solutions. The
      highest amount of albendazole was solubilized in the aqueous solution of Rofam
      containing 20 oxyethylene units. The increase in the content of oxyethylene units
      in a molecule of surfactant leads to a subsequent decrease in the amount of
      solubilized albendazole. Studied compounds can be applied in suggested quantities
      in the formulation of solid dosage forms. Tablets obtained with their content
      obeyed standards of Polish Pharmacopoeia. Rofams are increasing the amount of
      albendazole liberated from the tablets what can result in increasing it's
      bioavailability.

PMID- 16619796
TI  - [Evaluation of long-time resorption surgical sutures in tubal anastomoses with
      use of microsurgical techniques. An experimental study].
AB  - In the paper there have been evaluated synthetic absorbable surgical sutures-
      MAXON, of long time of their resorption in an organism. The valuation concerned
      their usefulness to carrying out the operations of oviducts with use of
      microsurgical technique. It consisted in determination of biocompatibility degree
      of analyzed sutures within tubal tissues and also their technical utility to this
      kind of procedures. The valuation of the surgical sutures was performed on the
      ground of experimental studies with use of laboratory animals--New Zealand white
      female rabbits, in which "end to end" microsurgical tubal anastomoses were made,
      with use of analyzed sutures. In further stage, pathomorphological investigations
      of the animals were performed (in various time after the operation), during which
      there were conducted microscopic observations of histologic slides derived from
      tubal anastomoses regions. The purpose of the work was trying to appoint the most
      adequate suture material for carrying out the operations of oviducts with use of
      microsurgical technique. It was also an assistance for an operator to take a
      decission of choice of the proper surgical sutures for surgical treatment of
      female mechanical infertility and other kind of microsurgical operations which
      are performed in gynaecology. Generally good technical utility in microsurgical
      practice of surgical sutures MAXON--absorbable of long period of their resorption
      in tissues was stated. They cause the formation of only single peritoneal
      adhesions, mainly in the regions of tubal anastomoses previously made and produce
      relatively small tubal tissue reaction, which testifies to high biocompatibility
      of the sutures, as the implantation material. The analyzed surgical sutures
      characterize themselves of very good usefulness to microsurgical operations of
      oviducts and they seem to be the most adventageous for performing this type of
      operations. They give a greater certainty of formation of durable accretion of
      tubal wall in the place of created anastomosis, with simultaneous complete
      elimination of the implantation material from the organism.

PMID- 16619797
TI  - [Biodegradable polymers for colon-specific drug delivery].
AB  - This review focuses on the colonic drug delivery, especially using biodegradable
      polymers i.e. guar gum, chondroitin sulfate, pectin, starch and amylose, dextran,
      chitosan, inulin. Basics of colon-specific targeting, formulation aspects,
      microflora influence and application of cross-linking techniques and polymer
      mixtures for targeting drugs into the colon are presented. Adventages and
      disadventages of colon-specific drug delivery are also described. A number of
      polymers is important in the context of colon-specific drug delivery.
      Considerable progress has been made over last three decades in this area.
      Although extensive investigations have to be done in the area of microflora
      endogenous ecosystems and enzymatic science, immunoactivity of biopolymers, and
      absorption enhancers for colonic mucous. Completely synthetic polymers of good
      swelling properties and sensitive to bacterial enzymes are also possible in the
      close future.

PMID- 16619798
TI  - [Biomaterials science. English vocabulary and its equivalents in Polish medical
      literature].
AB  - The ever-increasing use of biomaterials in many areas of medicine has led to a
      significant increase of reports concerning medical materials science. Much of the
      vocabulary used in English literature lacks proper unambiguous equivalents in the
      Polish language; inaccurate translations are frequent, leading to significant
      alterations of the meaning. The authors of this report have attempted to create a
      glossary of the terms pertaining to materials science most frequently encountered
      in herniological reports.

PMID- 16619799
TI  - [Visual evoked potentials (FVEP) after the prenatal exposure to heavy metals-
      experimentals studies].
AB  - PURPOSE: To find out, if any and how deep alterations in visual tract are due to
      prenatal intoxication by heavy metals such as: cadmium (Cd), lead (Pb), mercury
      (Hg) and manganese (Mn). The measure of these alterations were the changes in
      flash visual evoked potentials after prenatal intoxication. MATERIAL AND METHODS:
      The experiments were carried out on 55 white newborns Wistar rats, which were
      divided into 5 groups: control group (14 rats), Cd group (12), Pb (6), Hg (14)
      and Mn (9). The method of the FVEP study was described by Pojda et al. RESULTS:
      The latencies of the peaks N1 and P1 were prolonged in the Mn group till 113-118%
      (p< 0.05). Slight prolongation of N1 latencies about 1% in Cd and Hg groups and
      of 4% in Pb group were not statistically significant. The differences of P1
      latencies were not statistically significant in these groups, compared to the
      control group. The amplitude of N1 wave decreased in Cd group about 63% and in Mn
      group of 32% compared to the control (p<0.05). In Hg intoxicated group the N1
      amplitude decreased to 56% (p< 0.01). The amplitude of P1 decreased in all
      intoxicated groups (Hg of 56%, Cd 55%, Mn 49%) statistically significant, except
      the Pb one, in which even 21% decrease was not significant. CONCLUSIONS: The
      heavy metals prolonged the latencies and diminished the amplitudes of flash
      visual evoked potentials, so may be, they are not only neurotoxic but also
      "ophthalmotoxic" factors.

PMID- 16619800
TI  - Retinal dysfunction in eyes of patients with BRCA1 gene mutation.
AB  - PURPOSE: To assess the retinal function in BRCA1 gene mutation carriers. MATERIAL
      AND METHODS: Thirty unaffected patients (60 eyes) with constitutional BRCA1 gene
      mutation were studied. Flash ERG recordings were performed in accordance with the
      International Society for Clinical Electrophysiology of Vision (ISCEV) standards.
      RESULTS: In ERGs, in the maximal response, amplitude of a-wave (p<0.02) was
      reduced. In the cone single- flash response, the amplitude of a-wave (p<0.04) was
      also reduced. In the scotopic oscillatory potentials (OPs), we noted: increased
      amplitude of OP2 (p<0.0006), increased index of OP amplitude (01+02+03+04)
      (p<0.04), and increased latencies of OP1 (<0.05) and OP3 (p<0.004) and OP4
      (p<0.03). CONCLUSIONS: Slight dysfunction of rods, cones and inner retinal layers
      is present in asymptomatic carriers of BRCA1 gene mutation.

PMID- 16619801
TI  - Blood flow parameters in the arteries of the eye in premature children.
AB  - PURPOSE: of the study was to evaluate blood flow in the arteries of the eye in
      preterm neonates. MATERIAL AND METHODS: Color Doppler imaging (CDI) of ophthalmic
      artery, central retinal artery and posterior ciliary arteries was performed in 36
      preterm infants and 19 full-term infants. Maximal systolic velocity, end
      diastolic velocity, resistance index--RI and pulsatility index--PI were assessed
      for the studied vessels. RESULTS: There were no significant differences in
      ophthalmic artery blood flow between preterm and normal newborns. End-diastolic
      velocity in central retinal artery and posterior ciliary arteries in preterm
      infants was significantly lower and resistent index and pulsatility index was
      higher. The Doppler color ultrasonography is a non-invasive technique which can
      be useful for the estimation of the hemodynamic parameters in the arteries of the
      eye in the prematures. CONCLUSIONS: The recorded changes in the ultrasound
      measurements of the blood flow in the eye arteries in premature children
      comparing to the normal newborns, can be the evidence for the immaturity of the
      vessel system in the preterm born neonates.

PMID- 16619802
TI  - Visual function and late complications after cataract surgery by
      phacoemulsification with primary posterior capsulotomy and intracapsular foldable
      intraocular lens implantation.
AB  - PURPOSE: Evaluation of visual function and late complications after cataract
      phacoemulsification with primary posterior capsulotomy and intracapsular foldable
      intraocular lens implantation in 22-months follow-up. MATERIAL AND METHODS:
      Twenty five eyes of 25 patients (mean age: 53 years) were included in the study.
      All the eyes underwent primary posterior thermal capsulotomy and in-the-bag
      foldable IOL (Acrysof) implantation. Postoperative visual acuity and
      complications were analyzed. RESULTS: The best corrected visual acuity 1.0
      (Snellen chart) was achieved in 92% (23/25) of the eyes. The most frequent
      complication was a slight vitreous dislocation to the anterior chamber (4/25 of
      eyes--16%), resulting in the pupil deformation in two eyes (2/25 of eyes--8%). In
      one eye (1/25 of eyes--4%) retinal detachment was observed. None of the patients
      presented CME. CONCLUSIONS: A very good visual function and low rate of serious
      late complications suggest, that cataract phacoemulsification with primary
      posterior capsulotomy and in-the-bag foldable IOL implantation should be taken
      into consideration, as an option for preventing PCO. The results of the present
      study suggest the risk of retinal detachment and CME does not appear, to increase
      after the primary posterior capsulotomy. However, this conclusion has to be
      confirmed by randomized studies with longer follow-up period and larger series of
      patients.

PMID- 16619803
TI  - [Accuracy of the SRK II, SRK/T, Holladay and Hoffer Q IOL power calculation
      formulas in hyperopic patients after phacoemulsification].
AB  - PURPOSE: Comparison of the SRK II, SRK/T, Holladay and Hoffer Q formulas
      accuracy, in calculating IOL power in hyperopic patients. MATERIAL AND METHODS:
      34 eyes of 22 hyperopic patients, 15 women and 7 men, at the age from 19 to 85
      years old, after phacoemulsification with PCIOL implantation, operated between
      1998 and 2004 were analysed retrospectively. The power of IOL was calculated
      using the SRK/T formula and ranged from 28.5 to 35.0 D. The axial length ranged
      from 19.6 mm to 21.99 mm. The obtained refraction was measured with
      autorefractometer from 9 days to 37 month after operation, mean 6 month. In
      addition, the theoretical target refraction for the implanted IOL was calculated
      using the SRK II, Holladay and Hoffer Q formulas and the differences between the
      target and obtained refraction for all the formulas were compared. RESULTS: The
      best accuracy of IOL power calculation was obtained with the Hoffer Q formula.
      The Holladay, SRK/T and SRK II formulas gave worse results respectively.
      CONCLUSIONS: For the purpose of IOL power calculation in hyperopic patients the
      Hoffer Q or Holladay formula should be chosen from those mentioned above.
      Nevertheless, miscalculation exceeding 3D also happens in case of using them. The
      use of SRK II and SRK/T is not recommended. To improve the results other formulas
      utilising precise measurements of the anterior segment should be applied. If it
      is impossible then attention should be paid to improving traditional biometry
      measurements.

PMID- 16619804
TI  - [The results of diode laser treatment of retinopathy of prematurity].
AB  - PURPOSE: To evaluate the results of diode laser treatment of active phase of
      retinopathy in prematurity. MATERIAL AND METHODS: We studied 240 premature
      infants since January 2003 to October 2004. In 60 premature infants (102 eyes-
      25%) ROP was found. 26 premature infants (52 eyes--43.3%) with threshold ROP
      (stage 3a) in II zone (12 eyes) and in II and III zone (40 eyes) were treated
      with an aid of diode laser. Birth weight varied from 650 to 990g (mean 799.23g)
      and gestational age from 23 to 28 weeks (mean Hbd 26.2). RESULTS: Good anatomical
      results were obtained in 25 cases (50 eyes--96.15%), in 1 case (2 eyes--3.85%)
      was total retinal detachment. In this case the progress of retinopathy was caused
      by small birth weight and other chronic disorders. CONCLUSIONS: Diode laser
      treatment of active phase of retinopathy in prematurity gives good anatomical
      results. The results of treatment depend on the other chronic diseases of
      premature infants.

PMID- 16619805
TI  - [Surgical management of iris melanoma].
AB  - PURPOSE: To describe the own experiences of surgical treatment of iris melanomas.
      MATERIAL AND METHODS: 56 patients with iris melanoma were treated between January
      1995 and June 2001. Two surgical modalities were used depend on tumor location:
      partial iridectomy (in 45 cases) or transscleral iridotrabeculectomy (in 11 cases
      with the iridocorneal angle involvement). Additional ruthenium brachytherapy was
      performed in 3 cases. RESULTS: There were no any complications during surgery.
      Filtration bleb occurred in 1 patient during post-operative follow-up. Local
      recurrence of melanoma successfuly treated with ruthenium plaque appeared in one
      person. Histologically, the majority were spindle B melanomas (70%), mixed in 27%
      and epithelioid in 3%. The visual acuity was better or not changed in 90% of
      cases. CONCLUSIONS: Surgical management of iris melanoma seems to be save and
      effective treatment.

PMID- 16619806
TI  - [Surgical management of ciliary body melanoma].
AB  - The aim was to report my own experiences of the surgical treatment of ciliary
      body melanoma. 42 patients were treated by trasnscleral resection of melanoma
      between January 1995 and June 2001. Additional rutenium brachytherapy was
      performed in 29 cases. Intraoperative complications included bleeding (3 cases),
      vitreous loss (4) and retinal detachment (2). Residual tumor in one case was the
      reason of enucleation. Cataract surgery and intraocular lens implantation was
      necessary in 7 cases. Postoperative filtration bleb appeared in 6 eyes. The
      evaluation of functional results has shown no impairment of visual acuity in 56%
      of cases and did not change during follow up. These observations show that
      transscleral resection with additional brachytherapy is a method of choice in the
      management of ciliary body melanoma.

PMID- 16619807
TI  - [Visual acuity after surgical management of ciliary body melanoma].
AB  - The aim was to evaluate the visual acuity after transcleral resection of ciliary
      body melanoma. 42 patients were treated by trans-scleral resection of melanoma
      between January 1995 and June 2001. Additional rutenium brachytherapy was
      performed in 29 cases. Cataract surgery and intraocular lens implantation was
      necessary in 7 cases. Postoperative filtration bleb appeared in 6 eyes. The
      evaluation of functional results has shown no impairment of visual acuity in 56%
      of cases and did not change during follow up. These observations show that
      functional results after trans-scleral resection with additional brachytherapy
      are satisfactory and stable during follow-up.

PMID- 16619808
TI  - [Surgical management of choroidal melanoma].
AB  - The aim of this paper, was to report my own experiences of the surgical treatment
      of choroidal melanoma. 10 patients treated by transscleral resection with
      additional rutenium brachytherapy between January 1995 and June 2001, were
      evaluated in the study. Intraoperative complications included bleeding (3 cases),
      vitreous loss (3) and residual tumor successfully treated with iodine
      brachytherapy in one case. Postoperative retinal detachment with painful hypotony
      in one case was the reason of enucleation. The evaluation of functional results
      has shown no impairment of visual acuity in 20% of cases and did not change
      during follow up. These observations encouraged us in our belief that
      transscleral resection is an alternative method of treatment of choroidal
      melanoma.

PMID- 16619809
TI  - [Serum antiretinal antibodies (ARA) in patients with choroidal melanoma-
      preliminary report].
AB  - PURPOSE: To estimate serum antiretinal antibodies (ARA) in patients with
      choroidal melanoma after therapy in 3 months follow-up period. MATERIAL AND
      METHODS: 24 patients at the age 37-72 years (mean: 57.8 years) with choroidal
      melanoma were examined. In all cases routine ophthalmic examination with A- and B
      scan ultrasonography and fluorescein angiography were performed. In some subjects
      also indocyanine green angiography was performed. Ruthenium-106 plaques were used
      in 16 cases, in 5 cases treatment with Iodine-125 plaques was performed. Three
      patients underwent enucleation. In all cases ARA were determined in a serum
      dilution 1:10 by indirect immunofluorescence test on normal monkey retina as a
      substrate and FITC-labeled anti-human IgA, IgG, IgM serum (Euroimmun--Germany).
      ARA were scored before and within 3 months, after the therapy was performed.
      RESULTS: Before treatment ARA were present in 15 patients (62.5%) with choroidal
      melanoma in serum dilution 1:10. In a control group ARA were present in 3 cases
      (12.5%) in serum dilution 1:10. After therapy within 3 months follow-up period
      ARA occurred in serum of further 7 patients, all treated with Ruthenium-106
      plaques. Fluorescence of outer retinal segments was present in 7 cases, while
      serum of remaining 15 patients demonstrated positive reaction within the whole
      tissue. Indirect immunofluorescence test on normal monkey retina revealed in 11
      patients the presence of other autoantibodies; antinuclear and antinucleolar
      antibodies, reacting with nuclei of inner and outer nuclear layers of retina.
      CONCLUSIONS: The presence of ARA in serum of patients with choroidal melanoma
      before therapy may be a result of autoimmune reaction against the tumor tissue.
      The detection of ARA in serum after plaque therapy may be associated with
      reaction due to tumor irradiation. The appearance of other serum autoantibodies
      in patients with choroidal melanoma may indicate at more advanced and generalized
      process.

PMID- 16619810
TI  - [Indications for keratoplasty in District Railway Hospital in Katowice].
AB  - PURPOSE: The retrospective analysis of indications for keratoplasty. MATERIAL AND
      METHODS: The study of 517 keratoplasties between May 2000 and December 2004.
      RESULTS: The indications were: corneal oedema--24,5%, keratoconus--18,1%, corneal
      leucoma--15,0%, limbus insufficiency--10,2%, Fuchs endothelial dystrophy--9,0%,
      graft decompensation--8,1%, other acquired keratopaties--5,9%, corneal
      perforation--5,8%, anterior and stromal dystrophies--2,3%, Peters' syndrome-
      0,38%, choristoma--0,19%. CONCLUSION: Main indication for keratoplasty are
      corneal oedema and keratoconus.

PMID- 16619811
TI  - [Outcome results in macular hole surgery with internal limiting membrane
      removal].
AB  - PURPOSE: To determine the visual outcome and anatomic closure rate of macular
      hole surgery using pars plana vitrectomy with internal limiting membrane (ILM)
      peeling. MATERIAL AND METHODS: Fifty three eyes of 52 consecutive patients with a
      full-thickness idiopathic macular holes (stage 3 or 4). All eyes underwent a pars
      plana vitrectomy including separation of the posterior hyaloid, ILM peeling with
      trypan blue (TB) or indocyanine green (ICG) and gas endo-tamponade with
      instructions to the patient, to be face down for 4-5 days. Postoperative anatomic
      results, visual acuity (VA), and complications were recorded. The follow-up was 3
      to 22 months. RESULTS: VA improved postoperatively in 45 eyes (84.9%), at least
      two lines on the Snellen chart in 24 eyes (45.3%). It remained unchanged in 6
      eyes (11.3%) and deteriorated in 2 eyes (3.80%). The mean preoperative VA was 0.1
      +/- 0.04 and does not differ significantly between stage 3 and 4. The improvement
      of postoperative VA was statistically significantly better in stage 3, in
      comparison to stage 4. The anatomical success rate (flat/closed) was 88.7% (47
      eyes). There were no differences in VA improvement between TB- or ICG-stained
      eyes. CONCLUSIONS: 1. Vitrectomy with ILM removal in macular holes provides with
      meaning improvement in visual acuity. 2. Patients with macular hole in stage 3
      have a better prognosis for visual rehabilitation. 3. A kind of dye and
      preoperative VA do not influence postoperative visual function improvement.

PMID- 16619812
TI  - [The function of eye and vision system in children and youth treated with
      vigabatrin--our own experiences].
AB  - PURPOSE: The aim of this study is to find the relationship between visual
      function changes and vigabatrin treatment continuation or discontinuation.
      MATERIAL AND METHODS: 19 patients (11 males, 8 females) from 8 to 20 years old,
      treated with vigabatrin because of partial epilepsy, were examined. Best
      corrected visual acuity, contrast sensitivity and static visual field were done.
      The examinations were repeated after 1-2 months and after 1-2 years. The longest
      follow-up was about three years (one girl). In some children from this group
      additional elctrophysiologic tests (ERG, EOG according to ISCEV standards), were
      done. RESULTS: Corrected visual acuity was 5/5 in all eyes. Contrast sensitivity
      was normal and it was not changed in follow-up period. Abnormal visual field was
      found in more than half of examined patients. The improvement of visual field
      occurred after vigabatrin discontinuation, but in one patient the improvement
      occurred although vigabatrin treatment was continued. Most of the patients
      refused control ERG and EOG, but in first examination decreased or border b-wave
      amplitude after "flicker 30Hz" was found. CONCLUSIONS: In some patients treated
      with vigabatrin reversible visual field changes occurred. Multicentre study
      should be performed, to solve the problem of relationship between visual field
      changes, vigabatrin and other antiepileptic treatment. All tests in group of
      epileptic patients are difficult because of poor cooperation.

PMID- 16619813
TI  - [Visual evoked potentials in children with high blood lead level].
AB  - PURPOSE: The aim of this study is to find the relationship between lead level in
      blood (Pb-B) and visual evoked potentials (VEP) in children, environmentally
      exposed to lead. MATERIAL AND METHODS: 32 children (64 eyes) with no clinical
      signs of lead poisoning were examined. Corrected visual acuity was 5/5 in all
      eyes. Age of the children was 2-15.5 years (mean 8), Pb-B ranged from 150 to 486
      (mean 262) microg/l. For pattern VEP LKC equipment, UTAS E-2000 program and
      stimulations of 13', 26', 52', 105' were used. P100 amplitude and latency were
      calculated. RESULTS: P100 latency was significantly delayed in children at the
      age of seven, with Pb-B above 150 microg/l. The latencies were more delayed in
      children with higher than in lower Pb-B, but the relation was not linear. P100
      amplitudes did not differ significantly from the control group. In some children
      VEP had abnormal morphology, double P100 peak or P100 without sharp, but extended
      peak. CONCLUSION: Delayed P100 PVEP latency occurred in children with blood lead
      level higher than 150 microg/l, after at least 7 years of environmental exposure.
      Changes in VEP are similar to those which are caused by demyelinization and are
      found in multiple sclerosis.

PMID- 16619814
TI  - [Visual evoked potentials in children cured with sodium-calcium versenate because
      of high blood lead level--the prospective study].
AB  - PURPOSE: To find out if blood lead level (Pb-B) changes have influence on visual
      evoked potentials. MATERIAL AND METHODS: 18 children (36 eyes) treated with
      CaNa2EDTA because of chronic environmental lead poisoning were examined two
      times: first at age 2-15.5 (mean 8) years and second 4 years later. For pattern
      VEP LKC equipment, UTAS E-2000 program and stimulations of 13', 26', 52', 105'
      were used. P100 amplitude and latency were calculated. RESULTS: Pb-B was
      decreased from 150-486 (mean 262) microg/l to 42-248 (mean 103) microg/l. After 4
      years, P100 latency was significantly delayed in children with Pb-B above 100
      microg/l at second examination. In children with Pb-B below 100 microg/l no
      significant differences between two consecutive examinations were observed. There
      were no significant differences in P100 amplitude. CONCLUSIONS: Delayed P100
      latency of PVEP in children is permanent but non-progressive if Pb-B is lower
      than 100 microg/l.

PMID- 16619815
TI  - [Multifocal choroiditis and panuveitis (MCP)--diagnosis, ocular symptoms and
      treatment].
AB  - Multifocal choroiditis and panuveitis (MCP) belong to white dot syndromes, which
      are an idiopathic inflammatory process damaging the retinal pigment epithelium
      and choriocapillaris. We observed fourteen patients with typical ocular changes
      for MCP (panuveitis with typical multiple yellow, white or gray focal lesions in
      fundus of the eye). In 8 patients typically were observed--glaucoma, cataract,
      macular edema. We applied topical drops (corticosteroids, antiglaucomatous), and
      in 5 patients oral encorton was necessary to include.

PMID- 16619816
TI  - [Optical coherence tomography in Stargardt's dystrophy].
AB  - Stargardt's disease is one of the central retinal dystrophies with its onset in
      first two decades of life presenting gradual decrease in visual acuity and
      typical features in fluorescein angiography. The aim of the study was to evaluate
      the macular area in patients with diagnosed Stargardt's disease with the use of
      optical coherence tomography. 11 patients (22 eyes) were enrolled to the study.
      OCT examination revealed characteristic similar features of macular images in all
      patients. They included decreased thickness of the retina, most prominent in
      foveola, and changes in external retinal layers: lack of photoreceptors and
      nuclear external layer and changes in retinal pigment epithelium. Because of
      typical features in macular appearance, optical coherence tomography may become a
      useful tool for confirming diagnosis of Stargardt's disease.

PMID- 16619817
TI  - [Evaluation of state of the organ of sight in patients with diabetes type II].
AB  - PURPOSE: To evaluate the state of eyes in patients with diabetes type 2, and to
      gain current data about the presence of diabetic retinopathy, cataract,
      prevalence of particular types of retinopathy and percentage of people treated
      with laser photocoagulations. MATERIAL AND METHODS: The study included 1300
      patients, at the age from 18 to 91 years and treated for diabetes type 2 for the
      period between 1 and 46 years. The analysis was based on a full ophthalmologic
      examination. RESULTS: There was a significant decrease in visual acuity in
      relation to the duration of diabetes mellitus. In the whole group there were 474
      patients (36.46%) without diabetic retinopathy and 826 patients (63.54%), who had
      diabetic retinopathy. Non-proliferative, simple diabetic retinopathy was present
      in 605 patients (46.54%), pre-proliferative diabetic retinopathy was found in 171
      patients (13.15%), and proliferative retinopathy in 50 patients (3.85%). The
      study indicated a significant increase in the incidence of diabetic retinopathy
      in relation to the duration of diabetes, ranging from 27% in patients with
      diabetes lasting for about 1 year, to about 94% in patients with diabetes treated
      for about 30 years. An increase in the percentage of patients requiring laser
      therapy was also correlated with the duration of diabetes.

PMID- 16619818
TI  - [Changes in bacterial flora of conjunctival sac in patients prophylacticaly
      treated with antibiotic before cataract operation].
AB  - PURPOSE: The aim of the study was to estimate changes in bacterial flora of
      conjunctival sac changes in patients prophylacticaly treated with different
      antibiotics (chloramphenicol, gentamycin, ofloxacin, norfloxacin) before cataract
      operation. MATERIAL AND METHODS: The studied group consisted of 166 patients
      hospitalized for cataract surgery. The control group consisted of 33 persons,
      neither treated topically with antimicrobial drugs nor suffering from infectious
      or inflammatory diseases. On the first day and on the operation day conjunctival
      swabs were obtained and typical microbiological diagnosis was performed. During
      hospitalization only one antimicrobial drug was administrated topically
      (chloramphenicol, gentamycin, ofloxacin or norfloxacin) in the studied group.
      RESULTS: Prophylaxis with antibiotics before cataract surgery changes bacterial
      flora of conjunctival sac: quantitative changes were observed most frequently,
      but also hospital antibiotic resistant strains were detected. None of tested
      antibiotics caused total elimination of conjunctival flora in all patients.
      CONCLUSIONS: None of the antibiotics used in our study could cause total
      elimination of conjunctival flora. According to our results, the most effective
      antibiotics in prophylaxis before eye surgery are fluoroquinolones. Some patients
      before eye surgery have the pathogenetic conjunctival flora not causing the
      disease, yet increasing the risk of postoperative endophthalmitis.

PMID- 16619819
TI  - [Block resection with scleral flap rotation in ciliary body melanoma].
AB  - The aim was to present a case of ciliary body melanoma treated with block
      resection and scleral flap rotation. 49-year old woman with ciliary body melanoma
      and extrascleral extension appeared in our clinic. Block resection of ciliary
      body melanoma and scleral flap rotation was performed and additional ruthenium
      brachytherapy was applied. There was no complications during surgery and follow
      up. Described method can be recommended for openings in the sclera, which need
      emergency surgery.

PMID- 16619821
TI  - [Broken part of IOL haptic as a cause of bullous keratopathy. Case report].
AB  - Presentation of the case of the patient in whom 1 year after penetrating
      keratoplasty a broken, free moving haptic part of the IOL within anterior chamber
      was found. In accordance to increases of pain and high likelihood of donor
      corneal flap damage decision about surgical removal of free haptic was
      undertaken. Finding of the broken part of IOL throw light on the cause of bullous
      keratopathy in this case.

PMID- 16619820
TI  - [Capsule contraction as a cause of in-the-bag intraocular lens subluxation and
      simplified technique of IOL reposition].
AB  - Presentation of the case of the pseudophakic patient in whom 3 months after
      uncomplicated phacoemulsification severe capsule contraction syndrome, followed
      by equatorial capsule fibrosis, 240 degree zonular dialysis, and spontaneous in
      the-bag intraocular lens subluxation, were observed. Consecutive surgical
      intervention consisting of simplified transscleral "free haptic" through the
      capsule fixation and additional plastic of phimotic capsulorrhexis allowed to
      restore the best corrected visual acuity to 20/25.

PMID- 16619822
TI  - [Botulinum toxin injection to the lateral rectus for the treatment of intractable
      diplopia].
AB  - The aim of the study is to evaluate the use of botuline A (BTXA) as a form of
      treatment for squinting patients with onerous diplopia. Two patients with
      exotropia and one patient with esotropia had injections of BTX A to the lateral
      rectus muscles of the affected side. The number of injections ranged from 1 to 2.
      Two patients went on to have surgery. All patients in our study found that BTX A
      improved their symptoms of diplopia. We conclude that BTX A has an important role
      in the treatment of squinting patients with burdensome diplopia.

PMID- 16619823
TI  - [The visual acuity impairment as the only sign of cerebral aneurysms--case
      report].
AB  - Cerebral aneurysms are the most common reason of subarachnoid haemorrhage at the
      age of 50-60. Though the results of such haemorrhage are severe (high morbidity
      and mortality), it is quite often, the first noticeable sign of the problem.
      Previous symptoms i. e. headache, ophthalmic disturbances, temporary neurological
      symptoms are often passed over. The authors present the case of a young woman
      with cerebral aneurysms, in which the visual acuity impairment was the only
      symptom of the disease.

PMID- 16619824
TI  - [Central retinal vein occlusion in the tumor of colon and kidney--difficulties in
      diagnosis].
AB  - Central retinal vein occlusion (CRVO) is one of the commonest ophthalmic diseases
      of vascular background following systemic disorders. The complex etiology of the
      disease is often responsible for difficulties in establishing diagnosis.
      Trousseau was the first to describe in 1865 the increased risk of venous
      thrombosis in cancer patients. Segev et al. published the case of bilateral CRVO
      and colon cancer, which was not previously recognized. Another case of a patient
      with early symptoms of CRVO and generalized neoplastic disease, was identified in
      Department of Ophthalmology of Warsaw Medical University.

PMID- 16619825
TI  - [Necrotic central retinitis due to the lupus erythematosus].
AB  - We present a case of a twenty six years old patient who had been treated for
      systemic lupus erythematosus (SLE) for five years. The patient developed a sudden
      significant disturbance of vision quality of both eyes. A lot of additional
      examinations were done and central necrotic retinitis was diagnosed. After
      treatment insignificant improvement of vision quality of both eyes was achieved.

PMID- 16619826
TI  - [Quality of life in glaucoma patients].
AB  - Glaucoma as a chronic and often asymptomatic disease in its early stages has a
      great influence on Quality of Life (QOL). Mostly because of disturbances in
      visual functions like damage to the visual field, lower visual acuity, the
      psychological impact of the diagnosis, side effects and the cost of treatment.
      Evaluation of QOL is very useful instrument which helps to decide about the ways
      of treatment. Especially if they are equally beneficial but have totally
      different psychological impact. Considering patients' needs, satisfying their
      expectations and education, there is a guarantee of keeping the therapeutic
      indications and high efficiency of treatment.

PMID- 16619827
TI  - [Systemic management of autoimmune anterior uveitis].
AB  - Autoimmune uveitis is an acute, recurrent, sight-threatening disease that can
      lead to severe visual loss and blindness. It requires systemic immunosuppressive
      therapy and continuous monitoring by ophthalmologist and rheumatologist. There
      are no universally accepted referral patterns for the treatment of endogenous
      uveitis. Most specialists indicate corticosteroids, methotrexate and cyclosporine
      A as the first use drugs. Anti-cytokine drugs are a new opportunity for the
      patients unresponsive to the conventional anti-inflammatory and immunosuppressive
      therapy.

PMID- 16619828
TI  - [The role of retinal oxygen metabolism in origin of age-related macular
      degeneration (AMD)].
AB  - Age-related macular degeneration (AMD) is the leading cause of visual loss in
      individuals over 60 years old, in developed countries. This article provides the
      latest information about the role of retinal oxygen metabolism in origin of that
      disease. It is considered that reactive oxygen species (ROS), including free
      radicals are responsible for apoptotic cell death and developing of pathological
      changes in AMD. Exposure to visible light induces dysfunction of retinal pigment
      epithelial cells, accumulation of lipoprotein aggregates in Bruch's membrane,
      formation of drusen, and final results are damage to photosensitive retina, which
      leads to AMD. There are many of antioxidant systems in retina, which protect
      tissue from ROS. In this review we focus on their actions in terms of mechanisms
      of preventing oxidative damage and their potential role in therapy of AMD. There
      is strong evidence suggesting the supporting role of the nutritional antioxidant
      supplementation and protection from exposure to the visible light in the
      prevention and treatment of age-related macular degeneration.

PMID- 16619829
TI  - [Aberrometer systems in laser refractive surgery].
AB  - The wavefront sensing device provides a new and objective way of mapping the
      profile of refraction and of higher order defocus. Higher-order optical errors of
      the human eye are often responsible for reduced visual acuity, in spite of an
      optimal spherical or cylindrical refraction. These optical aberrations are of
      natural origin or can results from operations on the eye, involving optical
      structures. Nowadays, there are four different methods of wavefront technology
      available: Concept of "Outgoing" Reflective Aberrometry, Concept of "Retinal
      Imaging" Aberrometry, Concept of "Ingoing" Adjustable Aberrometry (Spatially
      Resolved Refractometer), Concept of "Double Pass" Aberrometry. Wavefront analysis
      is a more sophisticated method of defining aberrations that the surgeon is trying
      to correct through refractive surgery.

PMID- 16619830
TI  - [Demodex as an etiological factor in chronic blepharitis].
AB  - PURPOSE: To present and account the results of newest experimental and clinical
      investigations on the role of Demodex folliculorum and Demodex brevis in the
      etiology of chronic blepharitis. MATERIAL AND METHODS: A review of literature
      concerning the role of Demodex in the etiology of chronic blepharitis was done.
      RESULTS: It has been established that: (1) Demodex folliculorum and Demodex
      brevis occur among humans worldwide. (2) With age the prevalence of eyelids
      demodicidosis rises. (3) In the course of chronic blepharitis infection of
      Demodex folliculorum and Demodex brevis is often observed. CONCLUSIONS: Demodex
      is an etiological factor in chronic blepharitis.

PMID- 16619831
TI  - [Diagnostics and pharmacological treatment of ocular cicatrical pemphigoid].
AB  - Ocular cicatricial pemphigoid (OCP) is an autoimmune disease characterize by
      mucous membrane fibrosis and skin changes resulting with scarring. The pathogenic
      mechanisms of ocular cicatricial pemphigoid are incompletely understood.
      Antibasement membrane antibodies which lead to subepithelial blistering,
      granulation tissue and inflammatory infiltrate formation in the substantia
      propria are thought to be the main pathophysiological mechanisms in cicatricial
      pemphigoid. It has been found eosinophils and increased collagen type I and III.
      Human leukocyte antigen HLA-DR2, HLA-DR4 and DQw7 genotypes have been identified
      as conferring increased susceptibility to the development of this disease. Ocular
      cicatrical pemphigoid (OCP) is one of the forms of bullous pemphigoid. Initial
      symptoms of ocular pemfigoid are not characteristic. Conjunctival fibrosis may
      cause severe entropion, trichiasis, symblepharon, dry eye syndrome, corneal
      epithelial erosions or ulceration. Secondary glaucoma is one of the most frequent
      complications. Ocular cicatricial pemphigoid may be chronic, acute, or subacute
      disease with periodic exacerbation of conjunctival inflammation. The treatment in
      this disease are topical drops or ointment (lubricants, corticosteroids,
      antibiotics, antiglaucomatous). Oral dapsone and corticosteroids may control the
      activity of the disease. In other progressive cases immunosuppressive drugs must
      be used (azathioprine, cyclophosphamide, methotrexate, mycophenolan mofetil,
      daclizumab, intravenous immunoglobulin therapy). To make an early diagnosis of
      ocular cicatricial pemphigoid, biopsy and immunohistochemical analysis of
      conjunctiva should be performed in every case of persistent conjunctival
      inflammation.

PMID- 16619832
TI  - [Pentacam--the new way for anterior eye segment imaging and mapping].
AB  - Accurate preoperative measurements are required for refractive and cataract
      surgery. Pentacam is a new imaging system for anterior eye segment study. The
      authors present technique and the range of measurements; topography of both
      anterior and posterior corneal surface from limbus to limbus, densitometry,
      anterior chamber angle, volume and depth, lens densitometry and 3D-virtual model
      of the anterior eye segment are taken. All those structures are shown thanks to
      rotating Scheimpflug camera, which generates three-dimension images. Any eye
      movements are detected by a second camera and corrected for, in the process. All
      results are written down on PC and are available for the prospective studies.

PMID- 16619833
TI  - [A creator of modern surgery--Johann von Mikulicz-Radecki and contemporary
      ophthalmologists at the University of Wroclaw at the turn of the 19th-20th
      century].
AB  - The authors present the history of the life and achievements of Jan Mikulicz
      Radecki as the creator of modern surgery and his own school of surgery,
      especially during his work at the Wroclaw University in 1890-1905 years. The
      contemporary ophthalmologists as Richard Foerster, Hermann Ludwig Cohn, Wilhelm
      Uhthoff and theirs famous coworkers are also presented.

PMID- 16619834
TI  - [Louis Braille (1809-1852)--inventor of raised dots system].
AB  - Louis Braille was born on January 4th 1809 in Coupvray, France. An injury to his
      eye at the age of three, resulted in total loss of vision. In 1819 he entered the
      Institute for Blind Youth in Paris. There he would live, study, and later teach.
      When he was fifteen, he developed system of reading and writing by means of
      raised dots, which is known today as Braille. The basis of the Braille system is
      known as a Braille cell. The cell is comprised of six dots numbered in a specific
      order. Each dot or combination of dots represents a letter of the alphabet. This
      Braille system has established itself internationally and formed the basic
      Braille for all languages.

PMID- 16619835
TI  - [Long-term prognosis of the patients of myotonic dystrophy with tube feeding].
AB  - We studied the long-term prognosis of the patients of myotonic dystrophy with
      tube feeding. Subjects were 51 patients (31 male patients and 20 female patients)
      of typical myotonic dystrophy who were at least once admitted in our hospital. We
      examined the age of the introduction of tube feeding, the cause of the
      introduction, respiratory and motor ability at the introduction, the duration of
      tube feeding, the cause of death and the extension of CTG repeats in the
      patients. Comparing with the patients with tube feeding and the patients without
      it, we also examined the prognosis after the introduction of tube feeding. Tube
      feeding was introduced in 13 cases. The mean age of tube feeding was 57.9 +/- 8.3
      years old. The mean age of death of non tube feeding group was 55.9 +/- 5.5 years
      old. These show tube feeding was introduced in more elderly patients.
      Statstically the tube feeding was effective, but poor prognosis even after the
      introduction of tube feeding was suggested because the mean survival time after
      the introduction was about 850 days. We could not find any correlation between
      the age of the introduction of tube feeding and the extension of CAG report.

PMID- 16619836
TI  - [Diffusion-weighted magnetic resonance imagings at the acute stage in two
      patients with spectacular shrinking deficit due to cardioembolic stroke].
AB  - We report diffusion-weighted magnetic resonance imagings (DWI) at the acute stage
      of two patients with spectacular shrinking deficit (SSD) due to cardioembolic
      stroke. Patient 1 was a 74-year-old woman with atrial fibrillation (Af) who had
      been admitted for acute cholecystitis. She abruptly developed consciousness
      disturbance, global aphasia and right hemiparesis. Her neurological symptoms
      rapidly improved 30 minutes after onset, and completely disappeared in four
      hours. Patient 2 was a 84-year-old woman with Af who had been on medication of
      warfarin potassium for three years. She abruptly developed consciousness
      disturbance and left hemiplegia. Her neurological symptoms rapidly improved 90
      minutes after onset, and almost completely disappeared in ten hours. Their
      conditions were consistent with SSD in acute cardioembolic stroke. DWI of Patient
      1 taken 27 hours after onset showed hyperintense signal areas in the insular and
      temporal cortices of the left middle cerebral artery territory, and in the
      parietal cortex corresponding to the border zone between the territories of the
      left middle cerebral artery and posterior cerebral artery. DWI of Patient 2 taken
      39 hours after onset showed hyperintense signal areas in the insular and frontal
      cortices of the right middle cerebral artery territory, and in the parietal
      cortex corresponding to the border zone between the territories of the right
      middle cerebral artery and posterior cerebral artery. They indicated multifocal
      ischemic injuries at the acute stage. The T2-weighted MRI of Patient 2 showed a
      slight hyperintense signal area only in the right parietal cortex, but the fluid
      attenuated inversion recovery (FLAIR) in both patients showed no abnormal signals
      in the corresponding areas. To our knowledge, ischemic lesions in DWI of SSD at
      the acute stage after rapid recovery have not been reported previously. DWI is
      useful in SSD for detecting ischemic injuries of cardioembolic origin at the
      early stage.

PMID- 16619837
TI  - [Oral cyclophosphamide therapy for multifocal fibrosclerosis with hypertrophic
      intracranial pachymeningitis].
AB  - A 54-year-old man was admitted to our hospital because of a headache, dry cough,
      low grade fever and hearing loss sustained for 6 months. Physical and
      neurological examinations revealed bilateral conjunctival hyperemia, fine
      crackles in the lower lungs, cutaneous scars, horizontal gaze evoked nystagmus,
      bilateral moderate sensorineural deafness and mild hyperreflexia. Hypertrophic
      intracranial pachymeningitis (HIP) accompanied by episcleritis, pulmonary
      fibrosis, subcutaneous fibrosis of the trunk and upper limbs, bilateral chronic
      otitis media and sinusitis of the paranasal cavities were observed.
      Histopathological investigation of biopsied tissues from the dura matter, lung,
      skin and nasal mucosa showed marked fibrosis with lymphocyte and plasma cell
      infiltrations. The diagnosis of multifocal fibrosclerosis (MF) was made; this is
      a rare syndrome of unknown etiology characterized by fibrosis involving multiple
      organ systems. Although steroid pulse therapy and cyclophosphamide (CP) pulse
      therapy was not effective in his illnesses, the combination therapy of
      corticosteroid and oral CP was dramatically effective. We concluded that HIP can
      be a manifestation of MF, and additional oral CP should be considered as a
      treatment for steroid-resistant MF with HIP.

PMID- 16619838
TI  - [Siblings with xeroderma pigmentosum group A showing mild cutaneous and various
      neurological manifestations].
AB  - We report siblings with xeroderma pigmentosum group A (XP-A) showing mild
      cutaneous and late-onset severe neurological manifestations. The elder brother
      first noticed unstability in walking at 16 years of age. Subsequently slowly
      progressive mental deterioration developed with cerebellar ataxia, spasticity,
      sensory disturbance, urinary dysfunction and vocal cord paralysis. His younger
      sister presented with dysarthria at 18 years of age. She showed manifestations
      similar to her brother's. Both of them suffered from sensitivity to the sun but
      no malignant skin tumor. They were diagnosed as XP-A by the measurement of
      unscheduled DNA synthesis and complementation analysis. Gene analyses revealed
      compound heterozygote for G-->C substitution at the 3' splicing acceptor site of
      intron 3 and insertion of 4 bases in exon 6 of XPA gene. It is suggested that
      transcription-coupled repair is dominantly affected with relative sparing of
      global genome repair in these siblings.

PMID- 16619839
TI  - [Skin collagen abnormalities in a Japanese patient with extracranial internal
      carotid artery dissection followed by extracranial vertebral artery dissection].
AB  - A 41-year-old man with hypertension and hyperlipidemia who complained of left
      hemiparesis after a temporal headache was admitted to our hospital. A cervical
      MRI with gadolinium enhancement revealed an intramural hematoma is compatible
      with right extracranial internal carotid artery dissection. Two weeks later, he
      complained of sudden onset of pain in the right side of his neck. The right
      extracranial internal carotid artery dissection followed by the right
      extracranial vertebral artery dissection was diagnosed. Spontaneous cervical
      artery dissection (SCAD) is one of the causes of stroke in young adults. The
      pathogenesis of SCAD remains unknown. Minor trauma like an excessive sneeze,
      migraine, and connective tissue disorders such as fibromuscular dysplasia and
      Ehlers-Danlos syndrome are well-known as risk factors for SCAD. Pathologically
      skin collagen abnormalities have been seen in German patients with SCAD without
      clinical evidence for any specific connective tissue disorder. We examined the
      ultrastructural morphology of the Japanese patient's dermal connective tissue
      components by electron microscopy. The patient's collagen fibers contained
      fibrils with highly variable diameters, and there were other ultrastructural
      abnormalities, including flower-like fibrils and large-diameter composite
      fibrils. This is the first report of a case of ultrastructural abnormalities of
      dermal connective tissue in a Japanese patient with SCAD.

PMID- 16619840
TI  - [Anti-Yo antibody associated paraneoplastic cerebellar degeneration with gastric
      adenocarcinoma in a male patient: a case report].
AB  - We report a 71-year-old man presenting with paraneoplastic cerebellar
      degeneration (PCD) associated anti-Yo antibody after surgery for gastric
      adenocarcinoma. Seven months after partial gastrectomy, he deviated to the right
      on walking. Furthermore, a feeling of dysarthria appeared and he was unable to
      sit after 2 months. When he was hospitalized, he showed a disturbance of his eye
      movement on lower gaze, a nystagmus on lateral gaze, saccadic eye movement on
      smooth pursuit, cerebellar ataxia, and decreasing of muscle tonus in his
      extremities. However, no atrophic findings of the brainstem and cerebellum were
      revealed by brain MRI. He responded poorly to treatment with high-dose
      methylprednisolone, high-dose immunoglobulin, double filtration plasmapheresis
      and rehabilitation. There was a strong anti-Yo immunohistochemical staining of
      the cytoplasm in both the patient's tumor cells and normal cerebellar Purkinje
      cells. These findings suggest that PCD associated with anti-Yo antibody triggered
      by adenocarcinoma might occur in this male patient.

PMID- 16619841
TI  - [Three Japanese cases of hypnic headache].
AB  - We described three cases of hypnic headache with successful treatment by lithium
      carbonate or caffeine. This is the first detail report of Japanese cases. An
      endocrinological test and rhythm analyses of ambulatory blood pressure (ABP) and
      heart rate variability in a case suggested possible association between hypnic
      headache and hypothalamic-pituitary dysfunction. Case 1: A 48-year-old female
      migraineur complained of new-onset nocturnal headaches. Her headache awakened her
      from sleep between 1 AM and 2 AM. The headache occurred 3-4 times per week and
      lasted from 1 hour to 2 hours. The headache were moderate intensity and bilateral
      dull throbbing pain that located in the forehead to temples. There was no
      accompanying symptoms such as nausea, phonophobia, photophobia, nor the other
      autonomic features including conjunctival injection or tearing during the
      headache attacks. Physical and neurological examinations showed normal results
      except slight weakness and mild dysesthesia of the left arm due to a vertebral
      disk herniation at C5/6 level. In the pituitary endocrinological test, the
      prolactin level remarkably increased in response to the TRH loading. The single
      cosinor analysis demonstrated significant circadian rhythm of ABP parameters.
      However, the analysis did not demonstrate any significant circadian rhythm of
      Holter ECG parameters of time domain analysis and frequency analysis. Receiving
      200 mg lithium bicarbonate before sleep, her nocturnal headache completely
      disappeared. Case 2: A 68-year-old woman had been followed up by her chronic
      tension-type headache since her forties. At her 66-years, she suffered from a new
      nocturnal headache. She awoke from sleep by the headache about 3 AM and the
      headache lasted 30 min. Moderate, dull headache located on her left temple to
      parietal head, 3-4 times/week. She was able to go back asleep without any
      medication after spontaneous headache cessation. She first complained the
      nocturnal headache at the 10 months later of the new headache appearance. She
      received 200 mg caffeine just before sleep and her headache has been disappeared.
      Case 3: 70-year-old women had been regularly visited our clinics for her migraine
      and chronic tension-type headache. She received amitriptyline and her headaches
      was well controlled. At her 69 years, she complained nocturnal headache. It
      occured every other day. The headache was moderate pulsative dull pain on the
      occipital region and lasted 90 minutes without any autonomic symptoms. Headache
      began between midnight and 1 AM. She told us her new nocturnal headache one year
      later of the onset. Oral caffeine (200 mg) just before sleep did not improve her
      headache and caused insomnia. Receiving 100 mg lithium before sleep, her hypnic
      headache disappeared completely. These three cases are compatible with the
      diagnostic criteria proposed in ICHD-II. There were some patients with hypnic
      headache in Japan and neurologists should pay attentions to this form of benign
      headache, because some beneficial treatments are currently available.

PMID- 16619842
TI  - [A case report of streptococcus oralis meningitis after dental manipulation].
AB  - A 75-year-old man was admitted to our hospital because of high fever and
      disturbance of consciousness 4 days after dental treatment including scaling,
      irrigation, and oral antibiotic for dental caries without gingivitis. A lumber
      puncture revealed cloudy cerebrospinal fluid (CSF): it contained 984
      leukocytes/mm3, 680 mg/dl of protein, 5 mg/dl of glucose (blood sugar 233 mg/dl),
      and Streptococcus oralis, one of common microorganisms on the gingival, was
      isolated from the CSF. He was successfully treated with intravenous antibiotics.
      The authors believe this patient's meningitis developed as a result of bacteremia
      after the dental scaling in the present case.

PMID- 16619843
TI  - [A case of acute lymphocytic leukemia relapsed as meningoradiculoneuropathy after
      bone marrow transplantation].
AB  - We report a 21-year-old woman who had acute lymphocytic leukemia with a relapse
      in the peripheral nervous system after bone marrow transplantation. She developed
      gait disturbance and numbness of the lower limb extremities, with gradual
      worsening. Neurological examination detected paraparesis associated with
      areflexia and stocking-type paresthesia. An examination of the cerebro-spinal
      fluid detected leukemicells. T2-weighted MRI of the lumbar spine showed multiple
      hyperintense signal lesions at the bodies of vertebra, spinous processes, and
      pedicles. Based on the diagnosis of recurrent acute lymphocytic leukemia with
      tumor infiltration to the meninges (meningeal leukemia), she received
      chemotherapy, after which her neurological symptoms and signs gradually improved.
      We would like to emphasize that neurological examination is important to detect
      CNS relapse in a patient with leukemia, even in hematological complete remission.

PMID- 16619844
TI  - [Headache and neck pain as only manifestations of spontaneous of the dissecting
      aneurysm vertebral artery--a case report].
AB  - A 57-year-old woman had noticed occipital headache and neck pain bilaterally 6
      weeks before admission. The headache and neck pain persisted for 3 weeks, then
      disappeared. Cranial magnetic resonance (MR) image obtained 4 weeks after the
      onset demonstrated intramural hematoma adjacent to intracranial left vertebral
      artery. MR image did not show any abnormal lesions in the brain parenchyma.
      Although cranial MR angiography did not show any definite aneurysms, three
      dimensional CT angiography (3D-CTA) obtained 6 weeks after the onset disclosed an
      aneurysm of the left vertebral artery. The vessel distal to the aneurysm was
      occluded. Because the left posterior inferior cerebellar artery originated from
      the aneurysm, we did not perform embolization using coils. Spontaneous dissecting
      aneurysm of the left vertebral artery was diagnosed based on the clinical, MR
      image, and 3D-CTA findings. The systolic blood pressure was maintained under 130
      mmHg using antihypertensive agents. Thereafter, 3D-CTA obtained 6 months after
      the onset showed recanalization of the occluded vessel distal to the aneurysm.
      The size of the aneurysm was unchanged. During these 6 months, there were no
      ischemic or hemorrhagic stroke events. In the present patient, headache and neck
      pain were the only manifestations of spontaneous dissection of the vertebral
      artery.

PMID- 16619845
TI  - [Review of neurobehavioral effects of alcohol-related neurodevelopmental disorder
      in an animal model].
AB  - Animal models had been investigated to clear the mechanism of neurobehavioral
      deficits caused by in-utero alcohol exposure. 5-HT1A agonist and antioxidants
      administration during pregnancy could attenuate in-utero alcohol-induced
      teratogenesis. Recently, activity-dependent neuroprotective peptides were
      reported to have the potential therapeutic effect for alcohol-related
      teratogenicity. Environmental and motor training for litters exposed to in-utero
      alcohol may have improve behavioral performance. We will review amelioration of
      fetal alcohol-related neurodevelopmental disorders in animal models from the
      prevention and treatment.

PMID- 16619846
TI  - [Role of tissue plasminogen activator in the rewarding effect of morphine].
AB  - Tissue plasminogen activator (tPA) is a serine protease that catalyzes the
      conversion of plasminogen (plg) to plasmin. The tPA-plasmin system plays a role
      in synaptic plasticity and remodeling. In this review, we focused on the role of
      tPA-plasmin system in the rewarding effect of morphine. A single morphine
      treatment induced tPA mRNA and protein expression in a naloxone-sensitive manner,
      which was associated with an increase in the enzyme activity in the nucleus
      accumbens (NAc). The acute effect of morphine in inducing tPA expression was
      diminished after repeated administration. No differences were observed in the
      morphine-induced antinociceptive effect between wild-type and tPA knockout (tPA-/
      ) mice. Morphine-induced conditioned place preference and hyperlocomotion were
      significantly reduced in tPA-/- and pLg-/- mice, being accompanied by a loss of
      morphine-induced dopamine release in the NAc. Microinjection of either exogenous
      tPA or plasmin into the NAc significantly potentiated morphine-induced dopamine
      release in the NAc of ICR mice. In contrast, plasminogen activator inhibitor-1
      (PAI-1) dose-dependently reduced morphine-induced dopamine release. Furthermore,
      the defect of morphine-induced dopamine release and hyperlocomotion in tPA-/-
      mice was reversed by microinjections of either exogenous tPA or plasmin into the
      NAc. Our findings demonstrate a novel function of the tPA-plasmin system in
      regulating dopamine release in the NAc, which is involved in the morphine reward.

PMID- 16619847
TI  - [Role of the monoamine system in the brain on the development of psychological
      dependence on toluene].
AB  - Abuse of volatile organic solvents among youth remains a major social problem in
      Japan. Organic solvents are cheap and relatively easy to obtain, so they carry
      the risk of becoming a so-called "gate-way drug" for users. Psychological
      dependence assessment systems have been established for drug inhalation using the
      conditioned place preference (CPP) procedure. We found toluene produced the
      rewarding effect in this new CPP system. The mesolimbic dopamine pathway, which
      includes dopaminergic neurons in the ventral tegmental area (VTA) of the midbrain
      and their targets in the limbic forebrain, especially the nucleus accumbens
      (NAC), is one of the most important substrates for the development of
      psychological dependence on drugs such as stimulants, cocaine, and heroin.
      Recently, it has indicated that the VTA-NAC pathway (monoamine system) may play
      an important role of the expression of psychological dependence on the volatile
      organic solvent toluene. Clarification of organic solvent's mechanism for the
      development of psychological dependence focusing on the monoamine system can be
      exploited for the new medicine and useful treatments for dependence on toluene.

PMID- 16619848
TI  - [Study on suicide attempts among drug addicts--prevalence of suicide attempts and
      investigation of related risk factors].
AB  - While the relationship between substance use disorder and suicidal behavior is
      well known, few studies have been conducted on this issue in Japan to date. The
      present study aimed to investigate the profiles of drug-dependent individuals
      with a history of suicide attempts not including completed suicides. A survey was
      conducted on 101 drug-dependent patients in 8 drug rehabilitation institutions.
      The survey included a questionnaire that assessed various items regarding
      personal profiles, such as history of suicide attempts and drug abuse, physical
      and mental problems. In addition, the survey included the Parental Bonding
      Instrument (PBI) and the Center for Epidemiological Studies Depression Scale (CES
      D). The results indicated that 50 patients (49.5%) had attempted suicide, and
      that subjects with a history of suicide attempts were significantly younger than
      those without suicide attempts. It was also revealed that subjects with a history
      of suicide attempts had started abusing drugs at an earlier age, had more
      psychiatric problems, and scored higher on the CES-D and lower on both the
      parental and maternal care scores of the PBI. These findings suggest that early
      age drug abuse, psychiatric problems, depressive symptoms, and parental rearing
      behaviors perceived as cold and rejecting may predispose drug-dependent
      individuals to suicidal behavior.

PMID- 16619849
TI  - [Association between substance abuse problems and antisocial tendencies in male
      juvenile delinquents: A study using the Psychopathy Checklist, Youth Version].
AB  - AIMS: We examined an association between substance abuse problems and antisocial
      tendencies in male juvenile delinquents. METHODS: Subjects were 57 male
      adolescents consecutively incarcerated between December 2004 and February 2005 in
      a juvenile classification home. A self-reporting questionnaire was used to assess
      substance abuse problems in the subjects: Drug abuse problems were assessed by
      the Drug Abuse Screening Test (DAST-20), and alcohol abuse problems were assessed
      by the Quantities-Frequencies Scale (QFS). A semi-structured interview was also
      preformed according to the Psychopathy Checklist, Youth Version (PCL: YV).
      Associations between questionnaire responses and interview findings were examined
      using Pearson's correlation or Spearman's rank correlation test. RESULTS: Of our
      subjects, the 17.5% were recognized as a problematic drug abuser, and the 52.6%
      as a problematic drinker. Neither of the total DAST-20 nor QFS score was
      significantly correlated with the total PCL: YV score, and also with each score
      of the four PCL: YV subfactors. However, significant correlations were found
      between some items on the PCL: YV and the DAST-20 or QFS score. The DAST score
      was significant correlated with the PCL: YV item, "impression management"
      (rs=0.35, p<0.001), and the QFS score was significant correlated with "serious
      violations of conditional release" (rs=0.33, p<0.05) and "criminal versatility"
      (rs=0.48, p<0.001). CONCLUSION: More than a half of male juvenile delinquents had
      alcohol abuse problems. Alcohol intake may be considered to promote repetition
      and diversification of their antisocial behaviors, although overall antisocial
      tendencies were not associated with drug and alcohol abuse problems in male
      juvenile delinquents.

PMID- 16619850
TI  - [Development of effective detection method for Coxiella burnetii in mayonnaise by
      real-time PCR and investigation of C. burnetii contamination in commercial
      mayonnaise in Tokyo].
AB  - A PCR method for the effective detection of Coxiella burnetii in commercially
      available mayonnaise was developed. Sample preparations were isolated from 50 g
      portions of each mayonnaise product by four successive extraction steps in
      phosphate buffer with 2.0 M NaCl. These extracts were then centrifuged at 20,000
      x g for 60 min. DNA was isolated from the solution containing the precipitate
      with a commercial kit, and amplified quantitatively using real-time PCR that
      targeted the com1 region of C. burnetii. The recoveries of C. burnetii from 2
      kinds of commercial mayonnaise specimens, with a baseline control of 1 x 10(7)
      particles of the Nine Mile phase II strain, were 85.0 +/- 6.0% and 72.0 +/- 0.4%,
      respectively. The determination limit of this method was 500 C. burnetii
      particles per 50 g of mayonnaise. The DNA specimens isolated from 50 different
      commercial mayonnaise samples sold in Tokyo using this method were amplified
      using both nested PCR and real-time PCR. No contamination by C. burnetii was
      detected in any of the mayonnaise samples.

PMID- 16619851
TI  - Investigation of false-positive reactions for CBH351 maize in screening PCR
      analysis.
AB  - Examination for CBH351 maize was conducted by the qualitative polymerase chain
      reaction (PCR) method in maize grain and maize processed foods obtained in the
      Tokyo area. The numbers of samples possibly positive in the screening test were 7
      of 22 (31.8%) for maize grain samples, 4 of 14 (28.6%) for semi-processed foods,
      11 of 30 (36.7%) for canned products, 3 of 30 (10.0%) for maize snacks, 3 of 4
      (75%) for tacos and 1 of 3 (33.3%) for tortillas. However, CBH351 maize was not
      detected in the confirmation test. Therefore, the results of the screening test
      were false-positive. Since the reaction might have been caused by the base
      sequences of the 3'-end of primers CaM03-5' and CBH02-3' used in the screening
      test, a new primer pair was designed. The PCR products obtained with the new
      primer pair TMC2-5'--TMS2-3' were specific for CBH351 and were not obtained with
      barley, wheat, rice, RRS, Bt11, or Event176. Thus, the new primer pair shows high
      specificity. CBH351 maize was detected from samples containing at least 0.05% CBH
      351 maize DNA by using this primer pair.

PMID- 16619852
TI  - [Laboratory-performance study of quantitative PCR methods to analyze an approved
      genetically modified maize (Mon810 Line)].
AB  - A laboratory-performance study was carried out to investigate factors affecting
      the reliability of the quantitative PCR method to analyze an approved genetically
      modified (GM) maize (Mon810 line). Test maize powdered samples were prepared as
      blind samples containing a high (assigned value; 5.45%) or low (assigned value;
      0.35%) concentration of the Mon810 line. After confirmation of their homogeneity,
      they were provided to 27 laboratories participating in the collaborative study.
      The data were collected from all laboratories and statistically analyzed. Two
      laboratories, which used a Roche LightCycler (LC), reported significantly high
      test values. A further examination showed that the LC method is greatly affected
      by the equipment itself or PCR reagents, resulting in poor repeatability. On the
      other hand, some laboratories, which used ABI quantitative PCR equipment,
      reported erroneous test values. In these laboratories, the errors appeared to
      have been due to inadequate quality and/or yield of DNA. To identify factors
      affecting the test values, analysis of the measured values for the taxon-specific
      gene will be useful. Furthermore, the modified silica-gel membrane DNA extraction
      method made it possible to extract the required amounts of DNA more easily and in
      a shorter time than before.

PMID- 16619853
TI  - Accumulation of paralytic shellfish poison (PSP) and biotransformation of its
      components in oysters, Crassostrea gigas, fed with the toxic dinoflagellate
      Alexandrium tamarense.
AB  - As a part of our studies on the mechanism of uptake of paralytic shellfish poison
      (PSP) and the kinetics of its accumulation in bivalves, oysters Crassostrea gigas
      were experimentally contaminated with PSP by being fed with the toxic
      dinoflagellate Alexandrium tamarense for 2, 4, 6, 8 and 10 days. Temporal
      variations in the PSP contents and their profiles in oysters during the feeding
      experiment were monitored by high-performance liquid chromatography (HPLC) and
      the toxin profile of the oysters was compared with that of A. tamarense. Toxins
      excreted from the infested oysters into the seawater for 2 and 10 days were
      recovered and analyzed by HPLC. PSP toxicity rapidly appeared in the tissues of
      oysters and their toxicity levels reached 0.6 (0.3), 2.2 (1.1), 1.0 (0.5), 3.4
      (1.6) and 1.1 (0.5) MU/g (nmol/g) shucked meat at 2, 4, 6, 8 and 10 days,
      respectively. The accumulation rates of toxin, calculated from the total amount
      (nmol) of toxins expressed by the total cell number fed during the exposure
      period and the toxicity of the oysters, were 14.1, 18.7, 5.1, 14.9 and 3.2% for
      2, 4, 6, 8 and 10 days. During feeding experiments, the toxin profile of oysters
      changed substantially, showing marked differences from the proportions found in
      the toxigenic dinoflagellate used as food. The toxin components in this strain
      existed almost exclusively as beta-epimers, which accounted for 66.3 mol% of the
      total. This contrasts with the case of the oysters, where the beta-epimers
      represented 24.8, 29.8, 25.1, 27.3 and 25.2 mol% of the total at 2, 4, 6, 8 and
      10 days, respectively. The amount of gonyautoxin-1 (GTX1) accumulated in oysters
      increased linearly and slowly for 8 days and the maximum content of GTX1 reached
      51.3 mol%. The composition of GTX group compounds recovered from the seawater in
      which the oysters had been reared was a little different from that within the
      oyster tissues.

PMID- 16619854
TI  - [Requirement of guarantees for the quality of health foods having tablet and
      capsule shapes and for the safety of raw materials, according to the
      administrative guidance].

PMID- 16619855
TI  - 2004-based national population projections for the UK and constituent countries.
AB  - The 2004-based national population projections, carried out by the Government
      Actuary in consultation with the Registrars General, show the population of the
      United Kingdom (UK) rising from 59.8 million in 2004, passing 60 million in 2005
      and 65 million in 2023, to reach 67.0 million by 2031. In the longer-term, the
      projections suggest that the population will continue rising beyond 2031 but at a
      much lower rate of growth. The population will become older with the median age
      expected to rise from 38.6 years in 2004 to 42.9 years by 2031. With the current
      plans for a common state pension age of 65 for both sexes from 2020, the number
      of people of working age for every person of state pensionable age is projected
      to fall from 3.33 in 2004 to 2.62 by 2031.

PMID- 16619856
TI  - A methodology for estimating the population by ethnic group for areas within
      England.
AB  - This article-describes the methodology used to produce experimental estimates of
      the population of England, and its local authority districts, by ethnic group.
      The approach used is a cohort component methodology with population counts, and
      each component of population change, constrained to the Office for National
      Statistics (ONS) Mid-Year Population Estimates. Consideration is given to the
      modelling of the ethnic dimension of mortality; fertility (and the allocation of
      ethnic group to infants); switching between ethnic group categories; and the
      various aspects of migration, with particular attention given to the application
      of commissioned census data. A description and analysis of the estimates
      themselves will be the subject of a separate article in Population Trends.

PMID- 16619857
TI  - The oldest old in Great Britain: change over the last 20 years.
AB  - This article examines twenty-year trends in several demographic and socio
      economic characteristics of the oldest old. Using data obtained by merging
      consecutive waves of the General Household Survey (GHS), this study offers
      detailed descriptive and multivariate analyses of the use of selected health
      services and the living arrangements of the oldest old over the last 20 years.
      The results provide an insight into the characteristics of the oldest old and
      changes over time in the selected characteristics, that is, the increase in the
      proportion living alone and in hospital out-patient visits, in contrast with the
      stability in the proportion visiting their General Practitioner (GP).

PMID- 16619858
TI  - "Search for diabetes in youth".

PMID- 16619859
TI  - Demographics and characteristics of wheezing/asthmatic children with repeat
      emergency department visits in O'ahu, Hawai'i.
AB  - A profile of Hawai'i's pediatric asthmatic patients who repeatedly visit the ED
      is lacking. This multi-centered prospective study found that repeat ED
      utilization occurs more frequently in a particular subset of patients.
      Characteristics of the asthmatic cohort can help health care providers,
      caregivers, children, and their families understand and better manage asthma as a
      chronic condition and improve quality of life.

PMID- 16619860
TI  - Community outreach, training, and research: the Hawai'i/Pacific Basin area Health
      Education Center of the University of Hawai'i, John A. Burns SChool of Medicine.
AB  - The Hawai'i/Pacific Basin AHEC is a federal grant program that utilizes
      academic/community partnerships to recruit students to health careers, train
      students in rural and underserved areas, and assist with workforce development
      across the region. Ongoing activities and programs include 1) Outreach for
      recruitment to health careers for students from kindergarten through adulthood;
      2) Individual and interdisciplinary health professions student training in rural
      and underserved areas; 3) Community health education using distance learning; 4)
      Assessment of and efforts to improve recruitment and retention of providers in
      rural areas including continuing education; and 5) Health disparities research.
      The AHEC programs reach more than 4,000 individuals annually, helps to train more
      than 1,000 individuals a year and assist with placement of up to 20 providers a
      year in rural and underserved healthcare practices. This article describes the
      existing AHEC programs that are community based, community driven and inclusive
      of all who choose to participate. Collaboration is invited and necessary for
      success and future program development. Future areas for collaboration activities
      include increased statewide community health worker training, an expanded health
      careers pipeline, ongoing rural and underserved health needs assessments and an
      expanded training network for students in healthcare. Additional information is
      available at www.ahec.hawaii.edu.

PMID- 16619861
TI  - The research subject advocate at the University of Hawai'i Clinical Research
      Center: an added resource for protection of human subjects.
AB  - In early 2001 the National Institutes of Health (NIH) created the Research
      Subject Advocate (RSA) position as an additional resource for human subjects
      protection at NIH-funded Clinical Research Centers (CRCs) to enhance the
      protection of human subjects participating in clinical research studies. The
      purpose of this article is to describe the RSA position in the context of
      clinical research, with a particular emphasis upon the role of the RSA in one of
      the five CRCs funded by the NIH Research Centers in Minority Institutions (RCMI)
      program. Through participation in protocol development, informed consent
      procedures, study implementation and follow-up with adverse events, the RSA works
      closely with research investigators and their staff to protect study
      participants. The RSA also conducts workshops, training and education sessions,
      and consultation with investigators to foster enhanced communication and
      adherence to ethical standards and safety regulations. Although it is too early
      to provide substantive evidence of positive outcomes, this article seeks to
      illuminate the value of the RSA position in ensuring that safety of research
      participants is accorded the highest priority at CRCs. Based upon initial
      results, we conclude that the RSA is an effective mechanism for achieving the
      NIH's goal of maintaining the utmost scrutiny of protocols involving human
      subjects.

PMID- 16619862
TI  - Medical school hotline.

PMID- 16619863
TI  - A cancer profile for Hawai'i.

PMID- 16619864
TI  - [Myopia in Mexico].

PMID- 16619865
TI  - [Usefulness of the geographic information system (GIS) in the identification of
      contributing factors to lead blood concentrations in a population of Venezuelan
      children].
AB  - OBJECTIVE: To identify environmental factors that contribute to blood lead levels
      (BPb) in children living in an urban area in Valencia, Venezuela, using a
      Geographical Information System (GIS) as an association tool. MATERIAL AND
      METHODS: An analytical-ecological study was carried out. POPULATION: 60 children.
      DATA COLLECTED: Demography, potential sources of environmental lead and BPb
      concentrations. An association was made between environmental variables and BPb,
      using a buffer analysis. RESULTS: There was a statistically significant
      difference between BPb in males (11.1+/-3.1 microg/dl) compared to females (9.5+/
      2.7 microg/dl). Average BPb of children living within the buffer areas (10.7+/
      3.2 microg/dl) was higher than that of the rest of the children (9.9+/-2.5
      microg/dl). Children with BPb levels higher than the permissible limit who live
      in the southern region of the area studied had an average BPb significantly
      higher than the rest. The GIS enabled the identification of a soldering/welding
      shop as the nearest source of exposure to the male children's homes. CONCLUSIONS:
      GIS made it possible to recognize sources of lead exposure in the area and its
      association with the BPb levels of children that live near such sources. It is
      suggested to further evaluate additional factors that could influence the risk of
      lead exposure.

PMID- 16619866
TI  - [Body mass index and body image perception in a Mexican adult population: the
      accuracy of self-reporting].
AB  - OBJECTIVE: To evaluate the accuracy of the self-reported body mass index and body
      image perception in a population of Mexican adults. MATERIAL AND METHODS: In
      1998, in the state of Morelos, Mexico, participants in the longitudinal study of
      Mexican Social Security Institute workers "IMSS Cohort Study" responded to a
      baseline, self-administered questionnaire designed to collect a large variety of
      lifestyle risk factors for chronic diseases. Participants self-reported their
      body image by selecting the silhouette that best portrayed them, from a set of
      silhouettes ranked from 1 to 9. Participants also self-reported their current
      weight and height, unaware that direct measurements of weight and height were to
      follow. Four to eight months later participants were weighed and their heights
      were measured using standardized procedures. Spearman correlations were computed
      to analyze the correlation between self-reported and measured data. The Kruskal
      Wallis test was used to evaluate the magnitude of difference between measured and
      self-reported height, weight and body mass index (BMI) (measured minus self
      reported), by educational level and categories of age. Robust regression was used
      to evaluate the potential effect of specific individual characteristics on
      differences between measured and self-reported weight and height. Logistic
      regression analysis was used to evaluate the sensitivity, specificity, and
      predictive values for BMI. RESULTS: The study included 934 subjects, of which
      62.6% were female. Females had a mean measured height of 1.55 m (SD 0.06) and
      weight of 65.4 kg (SD 10.9), while males had a mean height of 1.67 m (SD 0.06)
      and weight of 77.7 kg (SD 12.5). The mean BMI was 27.4 kg/m2 (SD 4.3) (females:
      27.2 kg/m2 +/- 4.45; males: 27.8+/-3.87). The median of body image perception
      (BIP) was 5 (25th percentile=4; 75th percentile=6). Correlations between measured
      and self-reported height, weight, and BMI for all subjects were 0.94, 0.96, and
      0.90, respectively. The correlation between BMI and BIP was 0.64 (0.67 for
      females and 0.59 for males). Self-reported mean varied no more than 1.3 cm from
      measured height and no more than 3.17 kg from measured weight. Error estimations
      of height, weight, and BMI decreased with educational level. Sensitivity and
      specificity before adjusting self-reported BMI with overweight and obesity
      categories that were collapsed into one were 94.8 and 83.0%, respectively; for
      BIP, those values were 87.6 and 48.9%. CONCLUSIONS: The results suggest that self
      reported BMI and BIP can be useful indicators of an overweight condition in
      Mexican adults. The sensitivities and specificities associated with corrected
      self-reported BMI categories could be used to adjust odds ratios and relative
      risks, calculated from BMI levels derived from the self-reported BMI. Body image
      perception made it possible to correctly classify individuals with BMI > or = 25,
      showing that it may be a valid estimate for use in epidemiological surveys.

PMID- 16619867
TI  - [Inconsistent condom use among sexual workers in Ecuador: results from a behavior
      survey].
AB  - OBJECTIVE: Whilst existing data suggests that the HIV epidemic in Ecuador is
      concentrated amongst men who have sex with men (MSM), there is very little
      available information on the situation of key populations, i.e. those most at
      risk of HIV infection and/or transmitting the infection. In particular, there is
      very little known about sex workers (SWs), their rate of condom use and other
      behaviors and characteristics with respect to the risk of acquiring sexually
      transmitted infections (STIs). This study presents findings from a survey carried
      out with SWs in eight cities in Ecuador. MATERIAL AND METHODS: Using a cross
      sectional design, a questionnaire focusing on behaviours, attitudes and socio
      economic and demographic characteristics was administered to SWs in eight cities
      in Ecuador. These eight cities together account for the majority of the
      population in the country, and they were also identified as the locations with
      high reported levels of HIV. RESULTS: Information from a total of 2867 SWs was
      obtained, the majority were captured in their workplaces. Most of SWs interviewed
      carry out their activities in closed settings dedicated to sex work (i.e. not in
      the street). The average age of respondents was 28 (95%CI 27-29), and around half
      of them live with a male partner (married or not). The rate of condom use with
      the last client was 88% (82% consistently with the last three), whilst with
      regular partners it was 6%. A high index of life-skills, high socio-economic
      status and having an official document that allows them to work, were positively
      associated with condom use with clients (PR [CI95%] 1.40 [1.40-1.40], 1.37 [1.36
      1.37], y 7.26 [6.87-7.46], respectively). CONCLUSIONS: Whilst condom use with
      clients amongst Ecuadorian SWs is high, this diminishes if one analyzes
      consistent condom use and is notably low with respect to regular partners. Condom
      use appears to be related to variables that can be linked to interventions, e.g.
      life-skills and official permission to carry out sex work. It is, therefore,
      important to tailor interventions for this population so they maximize the
      likelihood to increase consistent condom use.

PMID- 16619868
TI  - [Mexico health care system's objectives: importance to its population and
      determining factors].
AB  - OBJECTIVE: To document the importance to Mexico's population of the five
      intrinsic objectives of Mexico's present health care system (SS) and describe
      some of the determinants of its evaluation; the purpose is to contribute elements
      for defining priorities and to support the fulfillment of said objectives.
      MATERIAL AND METHODS: This is a cross-sectional study to the importance for
      Mexican population of the five objectives of SS, considered intrinsic or final in
      the National Evaluation and Performance Survey. The dependent variable was the
      ranking given by the population surveyed to each one of the objectives, based on
      the question: Which SS objective do you believe is most important? The
      independent variables (nominal and categorical) were: state of residence, type of
      locality, gender, age, education, present employment, quality of present state of
      health, last occurrence when medical assistance was needed but not received,
      grade of satisfaction with the operation of the country's medical care system and
      satisfaction with one's own health. A univaried analysis was conducted and
      summarized using percentages. The chi square test was used to validate or reject
      the hypothesis according to whether the rank assigned by the population to the SS
      objectives is the same, regardless of which variables were used in the
      comparison. A multinomial (politomic) logistical regression model was also
      developed to correlate the effect of the independent variables employed in the
      study with the importance assigned by the population to the SS objectives. The
      reference category of the model was the objective of improving the health of the
      population. The analysis was conducted using the statistical package STATA
      version 7.0. RESULTS: From the population studied, 31.8% reported that the most
      important objective is to improve treatment within the health care system. In
      rural areas, 31.46% of the population thinks the most important objective is to
      improve health, a result related with the self-perception of one's present state
      of health and lack of medical care. The probability of preferring the objective
      of improving treatment over improving health, between the populations with
      average education and higher levels of education is, respectively, 10% and 16%
      greater than the population with no education. Among the population that works
      independently, 31.2% consider improving health the most important objective, a
      greater percentage than that reported by the population of business owners and
      the one consisting of public and private employees. CONCLUSIONS: In general
      terms, the population analyzed by this study considered the improvement of
      treatment within the health care system to be most important, which differs from
      that suggested by the PRONASA 2001-2006. It was indicated that the importance
      assigned to the objectives can vary according to the group analyzed, its
      characteristics and the influence of diverse external factors on the individual,
      as a result of which the null hypothsesis is rejected. Variations among the
      populations' evaluations occurred, in particular, between the objective of
      improving treatment within the health care system and that of the improvement of
      the population's health. The obtained results guide the steps for communication
      and the strengthening of the health care system in order to adjust itself to the
      expectations of the population and support the fulfillment of the established
      objectives.

PMID- 16619869
TI  - [Mechanisms for allocating financial resources after decentralization in the
      state of Jalisco].
AB  - OBJECTIVE: To analyze, from the decision maker's perspective, the financial
      resource allocation process of the health services of the state of Jalisco (SSJ,
      per its abbreviation in spanish), within the context of decentralization.
      MATERIAL AND METHODS: Through a qualitative approximation using semi-structured
      individual interviews of key personnel in managerial positions as the method for
      compiling information, the experience of the SSJ in financial resource allocation
      was documented. From September to November 2003, the perception of managers and
      administrators regarding their level of autonomy in decision-making was explored
      as well as the process they follow for the allocation of financial resources, in
      order to identify the criteria they use and their justifications. RESULTS: From
      the point of view of decision-makers, autonomy of the SSJ has increased
      considerably since decentralization was implemented, although the degree of
      decision-making freedom remains limited due mainly to high adminstrative costs
      associated with salaries. In this sense, the implications attributable to labor
      situations that are still centralized are evident. Some innovative systems for
      financial resource allocation have been established in the SSJ for the sanitary
      regions and hospitals based upon administrative-managerial and productivity
      incentives. Adjustments were also made for degree of marginalization and
      population lag, under the equity criterion. CONCLUSIONS: General work conditions
      and decision-making autonomy of the sanitary regions constitute outstanding
      aspects pending decentralization. Although decentralization has granted more
      autonomy to the SSJ, the level of decision-making freedom for allocating
      financial resources has been held within the highest hierarchical levels.

PMID- 16619870
TI  - [HIV/AIDS-related stigma and discrimination: the case of health care providers in
      Mexico].
AB  - OBJECTIVE: To analyze the social construction of stigma and discrimination
      processes associated with HIV/AIDS and people living with HIV/AIDS (PLHA), based
      on the perceptions of health care providers in three states of the Mexican
      Republic. MATERIAL AND METHODS: Qualitative and quantitative description.
      Observation at nine institutions; in-depth interviews (14) and surveys (373)
      directed to providers of health services. RESULTS: Seventy-five percent of
      providers reported having received training related to HIV/AIDS; however, notions
      persist as to patients being hopeless; discrimination due to the idea of risk
      groups; the immediate identification of living with the virus, having the
      syndrome and death; and specific lack of knowledge of forms of transmission.
      Twenty-three percent would not buy food from a PLHA and 16% think they should be
      banned from public services. With respect to confidentiality: 89% believe it
      should be maintained and 38% think that employers and administrators have the
      right to know about their employees' condition. Isolation, notes in clinical
      histories pointing to HIV, obligatory testing and delays in surgeries for PLHA
      were constant practices. The perception that men who have sexual relations with
      men and sexual workers decide their sexual practices marks the division between
      innocent victims and guilty ones, which determines the stigmatization and
      discrimination processes in health services. CONCLUSIONS: The design of
      strategies to decrease stigma and discrimination associated with HIV/AIDS demands
      the inclusion of an ethical debate about human rights and a structural focus
      regarding social conditions that go beyond the notion of risk behaviors.

PMID- 16619871
TI  - [Seroprevalence of syphilis in pregnant women in San Luis Potosi].
AB  - OBJECTIVE: To determine the seroprevalence of syphilis in pregnant women.
      METHODS: A seroepidemiologic survey was conducted in 1857 women giving birth at a
      general hospital in the city of San Luis Potosi, Mexico. RESULTS: Five women
      (0.27%) were diagnosed with syphilis at the time of delivery. Maternal factors
      associated with a greater likelihood of syphilis included older age, a higher
      number of pregnancies and living out of wedlock. CONCLUSIONS: The number of new
      bhorns exposed to syphilis during pregnancy in San Luis Potosi is underestimated.
      The results of this study support the need to identify syphilis in infected
      mothers at the time of delivery.

PMID- 16619872
TI  - [Notch signaling pathway and new strategies in cancer treatment].
AB  - The Notch signaling pathway plays a crucial role at different stages of cell
      development, such as proliferation, growth, differentiation, and apoptosis.
      Recent studies demonstrate that depending on the expression level and cellular
      context, the Notch receptors play a role in apoptosis resistance in malignant
      cells. These findings suggest that Notch signaling components may be a potential
      target in the development of new cancer therapies. This review describes the
      function of the Notch pathway and new strategies in the modulation of its signal.

PMID- 16619873
TI  - [Iron deficiency anemia among Mexican women on reproductive age. History of an
      unresolved problem].
AB  - OBJECTIVE: To describe the prevalence of iron deficiency anemia in the past 66
      years among Mexican women on reproductive age, and to analyze the efficacy of
      interventions implemented for its prevention and control. MATERIAL AND METHODS:
      Observational and clinical epidemiological studies as well as federal
      intervention programs published between 1939 and 2005 having original data
      related to anemia were reviewed using electronic databases (Medline and Artemisa)
      and manual searches. Keywords were anemia, iron deficiency, women, and Mexico.
      The quality of clinical trials was evaluated using the Jadad scale. Anemia
      prevalence tendency was analyzed using a linear regression weighted according to
      the sample size. RESULTS: Forty-six research studies were included, nine
      corresponded to clinical trials and four to federal-operative programs. Seventeen
      papers reported anemia prevalence in non-pregnant women and twenty-three in
      pregnant women. In the first group, weighted anemia prevalence had decreased from
      39.6 to 15.5%, whereas in pregnant women it decreased from 35 to 25%. Of the
      clinical trials, 55% were considered to be good quality studies. CONCLUSIONS:
      Anemia in women on reproductive age, particularly in pregnant women, is still a
      public health problem in Mexico. If the current conditions continue, it would
      take 57 years to eradicate anemia in non-pregnant and 121 years in pregnant
      women. It is necessary to evaluate intervention policies and conduct consistent
      studies in order to enable appropriate steps to be taken to control anemia.

PMID- 16619874
TI  - [Clostridium difficile: a reemerging pathogen?].

PMID- 16619875
TI  - [FUNSALUD project receives international award].

PMID- 16619876
TI  - Seroprevalence estimation and risk factors for A. marginale on smallholder dairy
      farms in Tanzania.
AB  - A cross-sectional serological survey of A. marginale was conducted on 200
      randomly selected smallholder farms in each of the Tanga and Iringa Regions of
      Tanzania between January and April 1999. Sera, from dairy cattle of all ages,
      sexes and breeds were tested for antibodies against A. marginale using an
      indirect enzyme-linked immunosorbent assay. Antibodies to A. marginale were
      present in cattle throughout the study areas and the overall prevalence was 20%
      for Tanga and 37% for Iringa. The forces of infection based on the age
      seroprevalence profile were estimated at 8 for Tanga and 15 for Iringa per 100
      cattle years-risk, respectively. In both regions, seroprevalence increased with
      age (beta = 0.01 and 0.017 per year of age, p < 0.005, in Tanga and Iringa,
      respectively). Older animals in Iringa were significantly and negatively
      associated with decreased seropositivity (beta = -0.002, p = 0.0029). Further
      results of logistic regression models reveal that geographic location of animals
      in Tanga was associated with seropositivity (odds ratio (OR) = 2.94, p = 0.005,
      for Tanga Rural and OR = 2.38, p = 0.066, for Muheza). Animals acquired as a gift
      in Iringa had higher odds for seropositivity than brought-in cattle (OR = 2.44, p
      = 0.005). Our study has identified and quantified some key risk factors that can
      guide planners devising disease control strategies.

PMID- 16619877
TI  - Differences in susceptibility between cattle and swamp buffaloes to infection
      with Fasciola gigantica.

PMID- 16619878
TI  - The prevalence of bovine hypodermosis in Kars province, Turkey.
AB  - A total of 1276 cattle from 76 farms in 8 villages were examined by palpation of
      the skin for evidence of hypodermosis. The effects of age, sex, breed, and colour
      of cattle on hypodermosis were investigated. The overall prevalence was 31.9%.
      The mean number of warble fly larvae on infested animals was 8.46. Hypodermosis
      infestations were encountered in all the villages visited. Within a herd, the
      intensity of infestion decreased with the age of cattle. Infestation rates of
      warble fly larvae were lower in native cattle, in females, and in piebald
      animals.

PMID- 16619879
TI  - Scavenging pullets in Burkina Faso: effect of season, location and breed on feed
      and nutrient intake.
AB  - A study on scavenging local (n = 64) and crossbred (n = 64) pullets was
      undertaken in the dry and rainy seasons in two villages in Burkina Faso: Korea in
      the arid northern Sahelian region and Bounouna in the sub-humid south. After 4
      weeks of scavenging, the birds were killed and the crop contents were subjected
      to physical and chemical analysis. Cereal grains, brans, green and dry forages,
      insects/worms and household leftovers were the main physical components. The
      proportion of cereal grains was higher in the rainy season, whereas the
      proportion of bran, peanut and sand/grit was higher in the dry season (p < 0.05).
      The proportion of kitchen waste and millet/milo grains was higher in local than
      in crossbred birds, whereas the opposite was the case for millet/milo bran (p <
      0.05). Rice and local beer residues were not found in the crops of birds from
      Korea. Dry matter, ash, crude fibre and potassium contents were higher in the dry
      season (p < 0.05), while calculated metabolizable energy content was higher in
      the rainy season (p < 0.05). There were no location or breed effects on chemical
      composition parameters (p > 0.05), except that potassium content was higher in
      Korea. Mean live weight at slaughter was 806 +/- 22.0 g (local breed) and 881 +/-
      22.0 g (crossbreds) (p < 0.05). Digestive organ weights, including contents, were
      higher for crossbred birds (p < 0.05). Gastrointestinal tract percentage was
      higher in the rainy season and in Bounouna (p < 0.05). The nutrient composition
      of the crop contents indicates the need for supplementation, particularly of
      protein, for higher levels of production.

PMID- 16619880
TI  - Production objectives and management strategies of livestock keepers in south
      east Kenya: implications for a breeding programme.
AB  - A survey of pastoralist and agropastoralist households in south-east Kenya was
      conducted to determine their production objectives and management strategies in
      order to optimize and extend a breeding programme for indigenous small East
      African Shorthorn Zebu cattle. The reasons for keeping cattle and the breed/trait
      preferences identified reflect the multiple objectives of the livestock keepers,
      with both adaptive traits and productive/reproductive traits rated as important.
      Although the Maasai and Kamba zebu (M&KZ) breeds were ranked highly with regard
      to adaptive traits, the population is considered to have been in decline over
      recent years. In order to promote the conservation and sustainable use of the
      M&KZ cattle, the formation of an open nucleus breeding scheme is recommended. In
      particular, such a scheme would be able to address several existing constraints
      (e.g. individual herds are very small and communal use of pastures/water makes
      controlled mating difficult). Such interventions would require the full
      participation of the livestock keepers, as well as ensuring that a holistic
      approach to species and breed attributes is taken into account in setting
      breeding goals, such that the full array of contributions that livestock make to
      livelihoods and the genetic characteristics related to these contributions are
      fully incorporated into the programme.

PMID- 16619881
TI  - [Avian influenza is coming-are you ready?].

PMID- 16619882
TI  - [A burden of influenza among children].

PMID- 16619883
TI  - [The importance of increasing activity among elderly].

PMID- 16619884
TI  - [Ernst Agugust Hillbom, founding member of Duodecim society].

PMID- 16619885
TI  - [Fractures of the ankle].

PMID- 16619886
TI  - [Candidiasis hypersensitivity syndrome-real or false].

PMID- 16619887
TI  - [Induced hypothermia improves prognosis after resuscitation from cardiac arrest].

PMID- 16619888
TI  - [Systemic treatment of eczemas].

PMID- 16619889
TI  - [Radiological findings of brain, connected to alcohol overuse].

PMID- 16619890
TI  - [Inflamed joint: how to examine].

PMID- 16619891
TI  - [Uncontrolled use of corticosteroid eye drops causing glaucoma and vision
      impairement for a young man].

PMID- 16619892
TI  - [Elevated blood pressure].

PMID- 16619893
TI  - [Jugular vein abnormality].

PMID- 16619894
TI  - [Secretory fistula in the scar tissue after inguinal hernia surgery].

PMID- 16619895
TI  - [International Network of Current Care Recommendation meeting in Lyon, December
      2005].

PMID- 16619896
TI  - [Care of patients with hip fractures].

PMID- 16619897
TI  - Nursing leadership: power, politics and gender: the role of emotional
      intelligence (EI).

PMID- 16619898
TI  - Core elements of programmatic research in nursing: a case study.
AB  - In this invited paper Tina Koch and Debbie Kralik present the establishment of a
      research program outside the precincts of a university and we ask Gary Rolfe to
      provide a commentary from the perspective of an academic. We argue that a
      dedicated research unit, with a clearly articulated philosophy and in response to
      research questions from clients, community and practitioners, provides the focus
      to drive the program. Although we have infrastructure from the RDNS Foundation,
      obtaining external funding to support our program is a central activity.
      Discernable outcomes of our collaborative inquiries are described as participants
      with whom we research narrate aspects of their experience, leading to enhancement
      of self agency and quality of life. We illustrate the reform potential as groups
      of research participants develop sustainable people networks. Most importantly,
      theoretical development is ongoing describing transition (ways in which people
      are able to take a chronic illness into their lives and move on) and better
      understanding on ways in which health care professionals can facilitate
      transition. Evidence based news letters are written in collaboration with
      practitioners, however we ponder about ways to further our research findings in
      practice. Gary Rolfe speculates about intermural or extramural research programs.
      He frames his response using Brand's criteria to research program decisions. In
      order of importance he asks: (1) will it be fun? (2) will we learn anything from
      it? (3) will it make the world a better place? (4) will it earn enough money to
      pay for the first three? Gary argues that one of the luxuries of working within
      the university sector as an academic is that he can occasionally ignore question
      four.

PMID- 16619899
TI  - Transformative teaching in nursing education: preparing for the possible.
AB  - In these fractured and unsettling times, it is tempting to see nursing as a
      profession in crumbles. Many nurses are vocalising to media and to each other
      that they are overworked, underpaid, undervalued and intending to leave the
      system. Now more than ever, leaders, thinkers and change agents must organise
      themselves to restore life and vitality to the profession. Nursing educators are
      cornerstones in this restoration work, yet we too can at times feel overwhelmed
      and helpless to find engaging approaches to teaching nursing. This is the first
      of two papers, which argue that critical education is an illuminating philosophy
      for nursing. It can restore optimism and provide clear directions to assist
      neophytes and lifelong learners in nursing to become more self-confident, self
      determining, optimistic, resistant and change oriented. In this article, the
      context for learning is considered, exploring transformative teaching as one
      choice among several learning models. The article offers strategies nurses may
      use to prepare a fertile ground for learning wherever that may be located.

PMID- 16619900
TI  - Design, format, validity and reliability of multiple choice questions for use in
      nursing research and education.
AB  - Multiple choice questions are used extensively in nursing research and education
      and play a fundamental role in the design of research studies or educational
      programs. Despite their widespread use, there is a lack of evidence-based
      guidelines relating to design and use of multiple choice questions. Little is
      written about their format, structure, validity and reliability of in the context
      of nursing research and/or education and most of the current literature in this
      area is based on opinion or consensus. Systematic multiple choice question design
      and use of valid and reliable multiple choice questions are vital if the results
      of research or educational testing are to be considered valid. Content and face
      validity should be established by expert panel review and construct validity
      should be established using 'key check', item discrimination and item difficulty
      analyses. Reliability measures include internal consistency and equivalence.
      Internal consistency should be established by determination of internal
      consistency using reliability coefficients while equivalence should be
      established using alternate form correlation. This paper reviews literature
      related to the use of multiple choice questions, current design recommendations
      and processes to establish reliability and validity, and discusses implications
      for their use in nursing research and education.

PMID- 16619901
TI  - Australian nurses and child protection: practices and pitfalls.
AB  - Most Australian states have child protection legislation mandating individuals
      and groups to notify suspected child abuse and neglect. Nurses are legally bound
      to report their suspicions of child abuse and neglect in a number of Australian
      states, with South Australia, New South Wales, Victoria and Tasmania specifically
      identifying nurses as mandated notifiers. While the unique role of nurses puts
      them in a valuable position to detect and report suspected child abuse, aspects
      of the role may lead to conflict in detecting and notifying child abuse and
      neglect. This paper addresses some key practice issues for Australian nurses as
      mandated notifiers. These issues include: knowledge and education about child
      protection; organisational influences on nurses' participation in child
      protection; concerns about consequences of suspecting and notifying; protecting
      the therapeutic relationship; and interaction with other professionals.

PMID- 16619902
TI  - Medication errors and professional practice of registered nurses.
AB  - This Australian study identified and described the incidence of medication errors
      among registered nurses, the type and causes of these errors and the impact that
      administration of medications has on the professional practice of registered
      nurses. Mostly, medication errors were attributed to documentation issues,
      including: illegible handwriting, misunderstanding abbreviations, misplaced
      decimal point, misreading and misinterpreting written orders. Several human
      factors were attributed to potential causes of medication errors, including:
      stress, fatigue, knowledge and skill deficits. Environmental factors, namely,
      interruptions and distractions during the administration of medications, were
      also attributed to potential errors. The study found professional nursing
      practice involving administration of medications had a strong education, patient
      and ethical focus. Over a quarter of the respondents indicated that further
      training in medication administration would positively impact on their nursing
      practice. The registered nurses also highlighted they would appreciate more time
      to spend with patients when administering medications. Medication errors are not
      the sole responsibility of any single professional group, therefore,
      collaboration with other health professionals is central to establishing
      processes, policies, strategies and systems that will reduce their occurrence.
      The organisation and those nurses employed within it share an accountability to
      ensure safe administration of medications to patients. Based on study results,
      several recommendations are directed towards preventing or reducing medication
      errors and supporting nurses in providing best practice.

PMID- 16619903
TI  - Assessing cardiovascular status: a guide for acute care nurses.

PMID- 16619904
TI  - Cancer remains a leading cause of death in Australia.

PMID- 16619905
TI  - Leading opinion: grasping the nettle--a return to general registration
      examinations?

PMID- 16619906
TI  - Nursing research programs gather strength in Australia.
AB  - To shed light on programmatic research through direct experience is highly
      beneficial to nursing scholarship. Following a recent description of a successful
      Australian program of research centered around people's chronic illness
      experience we are inspired to continue the commentary (Koch et al 2005). Koch et
      al's (2005) case study reported on several 'core elements' they believe have
      contributed to the growth and effectiveness of their program. In this paper we
      consider some of these in light of current literature and our own challenging
      experiences within several Australian universities. Koch et al (2005) also makes
      a not too subtle distinction between dedicated research units independent of
      universities and research programs emanating from academia, suggesting the former
      are more productive. While one of the authors in the above paper, a UK scholar
      and nursing academic, makes interesting observations about this assertion, we
      contend that his UK perspective fails to capture the urgency of establishing
      nursing research programs in Australian universities. Consequently, we have
      chosen to extend the discussion about nursing research programs from the
      perspective of Australian academe, including comment on building productive
      relationships, strengthening a track record, research and practice as symbiotic
      processes, competitive funding strategies, and the integral role of research
      students. The entire commentary is located in a celebratory context of 20 years
      of Australian nursing education in the university sector, a context not without
      controversy. We give consideration to the best way ahead for the future of
      nursing research programs and hope our ideas spark further sharing of
      experiences.

PMID- 16619907
TI  - Transformative teaching in nursing education: leading by example.
AB  - This is the second in a pair of articles exploring critical education, an
      illuminating philosophy relevant to practice development facilitators, clinical
      teachers, academics, clinicians and others involved in the rethinking of nursing
      practice. I argue that critical education and its practice equivalent
      transformative teaching and learning, can restore optimism in those who feel that
      longstanding practice problems have become insoluble. It can provide clear
      direction to assist new nurses, students and lifelong learners to become
      strategic about change, aware of the rich and varied history of their profession,
      critical thinkers and creative solution generators. In this article, I move
      beyond the forming phase of the teacher-student relationship to the building, or
      working phase of learning. Two particular ways of encouraging critical thinking
      are emphasised: reflective practice and dialectical critique. In order to move
      beyond the purely abstract, I draw on my experiences teaching undergraduate and
      postgraduate students, and clinicians working in education, practice and
      research.

PMID- 16619908
TI  - Mentoring for nurses in general practice: national issues and challenges.
AB  - This paper reports the findings of a research project designed to identify
      national issues impacting on the development of a mentoring framework for nurses
      in general practice in Australia. The project comprised the first phase of a
      three-phase study commissioned by the Australian Government Department of Health
      and Ageing to develop a contemporary, flexible and sustainable mentoring
      framework that enhances the capacity of nurses to contribute to general practice
      outcomes. Key stakeholders and influential informants from around Australia were
      brought together via a national teleconference to identify issues surrounding the
      development of such a framework. Outcomes focussed on major themes concerning
      choice, relationships, structures and resources. Here, we consider the issues and
      challenges identified in light of some contemporary case studies from outside the
      field of nursing in the hope of sparking new ideas and strategies. A case study
      from an Australian practice nurse is included. No research has been conducted on
      mentoring for nurses in general practice in Australia to date, highlighting an
      urgent need for new models and their evaluation.

PMID- 16619909
TI  - Factors that influence the recruitment and retention of graduate nurses in rural
      health care facilities.
AB  - Rural nursing is a distinct practice and rural nurses in Australia constitute the
      largest group in the rural health workforce. However, the rural workforce is
      ageing and the turnover of nurses in rural areas is high. In addition, rural
      health services are experiencing recruitment and retention difficulties; very
      little is known about the recruitment and retention of new graduates nurses in
      rural health areas and the potential long-term investment they could offer to
      rural health services. A qualitative study explored the journey of transition for
      new graduate nurses employed in graduate nurse transition programs in northern
      New South Wales. This paper presents two major themes from the study that
      describe the factors that influenced the new graduate nurse to seek and accept a
      graduate nurse position within a rural health setting and the factors that
      influenced their retention. Findings indicate that previous connection with a
      rural area and positive experiences in a rural health care facility during
      undergraduate preparation were significant factors influencing the graduate
      nurses' decision to pursue a rural graduate nurse position. No guarantee of a
      permanent appointment upon completion of the graduate program, and graduates'
      disappointment with graduate nurse programs, were important factors influencing
      their retention within rural health care facilities.

PMID- 16619910
TI  - Perceptions of psychosocial support groups by parents who have a child with
      diabetes: a needs analysis.
AB  - Psychosocial support groups play an important role in assisting parents to
      understand and manage the demands of having a child with diabetes. Actual
      participation in such groups is marred by problems of poor uptake, irregular
      attendance and attrition. A survey was conducted with a convenience sample of
      parents to determine their knowledge needs about preferred program
      characteristics, the management of diabetes, perceived barriers to program
      participation, and factors facilitating group attendance. A response rate of 66%
      (n = 40) was achieved. Parents favoured a program that was only conducted monthly
      or three to six times a year, held during the evening or weekend and of two or
      three hours duration. Parents were keen to know more about new developments in
      the treatment of diabetes, and strategies to assist their child when they refuse
      medication or treatment. The most commonly reported barriers to group attendance
      were distance, timing of groups, and employment demands. Participants were more
      likely to attend a support group in order to learn new information or skills,
      keep up to date, as well as meet parents in the same situation. Support groups
      need to address both content and practical issues for enhanced support and
      empowerment of families.

PMID- 16619911
TI  - Nurse-academics' mentorship: rhetoric or reality?
AB  - Mentorship is generally identified in nursing literature as a positive strategy,
      and one that is said to be beneficial in increasing scholarly productivity.
      However, previous studies investigating the relationship of mentoring to
      scholarly productivity have produced equivocal findings. This relationship was
      examined as part of a study that considered constraints and/or facilitators of
      scholarly productivity among nurse academics. A survey questionnaire technique
      was used to establish current scholarly productivity levels, and frame and factor
      facilitating theory and analysis to identify major constraints and facilitators.
      Findings showed that while the majority of participants perceived mentoring as
      important to developing and increasing scholarly productivity, this was less so
      as academic rank increased. More than a quarter reported never having had a
      mentor. The burden of teaching and administrative over-load, and a cultural
      climate of non-support, were described as major disincentives to mentoring.
      Mentoring was more likely to occur where a collaborative and collegial network to
      support scholarly productivity existed. However, often it was seen as not
      available. A workplace environment that is appropriately supported by adequate
      resources may be as important as the research training that can occur through
      mentoring.

PMID- 16619912
TI  - No return to State licensing examination.

PMID- 16619913
TI  - The role of stories in understanding life events: poststructural construction of
      the 'self'.
AB  - An appreciation of the construction of the 'self' has the potential to enhance
      nursing practice. The 'self' within post-structuralism is fashioned through the
      social discourses and beliefs of the day. These socio-cultural determinants shape
      the individual and provide meaning for life events. Storytelling and the sharing
      of stories about these events play a key role in this process. In integrating
      narrative stories about 'self', individuals are provided with a link to their
      culture and cultural practices. Events, such as accommodating change or coming to
      terms with an illness diagnosis, require complex adjustments to the individual's
      already held identity of 'self'. Sharing stories plays a part in this adjustment
      and is the principal means by which individuals make sense of their experiences.
      This understanding of storytelling when caring for patients can encourage the
      nurse to exchange stories in order to provide opportunities for patients to tell
      their own stories.

PMID- 16619914
TI  - The international classification for nursing practice: a tool to support nursing
      practice?
AB  - Nurses have been slow to realise the uniqueness of their data and the importance
      of data management across the profession. This has resulted in nursing being
      neglected as a partner in healthcare because the data nurses collect cannot be
      easily retrieved from the patient record and is not widely used to support
      nursing practice. Nurses, as they should, have rejected language classification
      systems that are inadequate or inappropriate, but with the implementation of
      electronic health records, consensus on language classification must be achieved.
      One problem has been finding an appropriate terminology/s that represents the
      spectrum of nursing practice while making sense to both the user and computer. In
      1989 the International Council of Nurses began work to achieve this and the
      International Classification for Nursing Practice (ICNP) was born. This paper
      provides an insight into language classification, explores the ICNP as a tool for
      nursing practice and discusses some of the projects undertaken thus far.

PMID- 16619915
TI  - The role and scope of the Clinical Nurse Consultant in Wentworth Area Health
      Service: a qualitative study.
AB  - New South Wales Health introduced the role of the Clinical Nurse Consultant in
      1987. A review of the role was undertaken by an area health service in Western
      Sydney, NSW, Australia in 1992 and a number of issues were highlighted in the
      review process, including diverse roles and responsibilities. In 2000, New South
      Wales Health acknowledged the diversity of roles and developed a grading system
      based on five domains of practice. This paper reports the second phase of a two
      part study that investigated the scope of practice and perceived level of
      organisational support provided for the Clinical Nurse Consultants in the area
      health service. Focus group interviews, one for managers and two for nurse
      consultants, were conducted in order to collect data. Ten Clinical Nurse
      Consultants, representative of each grade and seven managers, covering various
      clinical streams, took part in the study. Data were analysed using content
      analysis and coded using constant comparison and contrast of codes. Results of
      the study reveal a lack of clarity and understanding of the new grading system.
      There is an indication that the role is very individual and the incumbents are
      often overloaded by work and the maze of demands put on them by numerous
      competing forces. Many of the Clinical Nurse Consultants felt they were working
      at a grade higher than their position classification. There appears to be a
      significant need to clarify the roles of each of these members of the health care
      system and to provide a better reporting scheme.

PMID- 16619916
TI  - Seeking evidence of rehabilitation in nephrology nursing.
AB  - Individuals with renal failure experience many varied and complex alterations in
      their health status. As a consequence, rehabilitation is an important aspect of
      their care. However, until recently, rehabilitation has not been explicit in the
      published nephrology nursing literature. This paper addresses that deficit
      through an examination of Australian nephrology nursing competency standards for
      evidence of rehabilitation. Recent Australian research about rehabilitation
      nursing practice was used as a guiding definition of rehabilitation. A systematic
      examination of these documents revealed evidence of rehabilitative practices
      embedded in the nephrology nursing competency standards' domains of empowerment
      and clinical problem solving. These findings add support for the belief that
      rehabilitation is a philosophy that all nurses can apply in their practice.

PMID- 16619917
TI  - Meeting the challenges of recruitment and retention of Indigenous people into
      nursing: outcomes of the Indigenous Nurse Education Working Group.
AB  - It has been recognised internationally that increasing the number of Indigenous
      people working as health professionals is linked to the improved health status of
      Indigenous people. When comparing Australian Indigenous and non-Indigenous
      populations, Indigenous people continue to have poorer health standards and are
      much less likely to be involved in employment in health professions than other
      Australians. In 2000, the Indigenous Nurse Education Working Group (INEWG) was
      formed by government with the mandate to work collaboratively with universities
      and important professional nursing bodies across the nation in an attempt to
      increase the number of Indigenous registered nurses and to prepare nursing
      graduates with better understanding of, and skills to assist with, Indigenous
      health issues. This paper describes the work of the INEWG from 2000 to mid-2003;
      firstly in developing and implementing strategies aimed at increasing the
      recruitment and retention of Indigenous people into undergraduate nursing
      programs; and secondly by helping university schools of nursing increase faculty
      and student understanding of Indigenous culture, history and health issues
      through educational processes. Lastly, it summarises the INEWG's 2002
      recommendations to achieve a higher rate of Indigenous participation in nursing.
      The results of research into the success of these recommendations will be the
      subject of a later paper.

PMID- 16619918
TI  - Managing delirium in older people.

PMID- 16619919
TI  - Nursing and a new (inter)national agenda.

PMID- 16619920
TI  - Response to: grasping the nettle--a return to general registration examinations?

PMID- 16619921
TI  - Response to: grasping the nettle--a return to general examinations?

PMID- 16619922
TI  - In search of the Holy Grail: a reply to Sioban Nelson.

PMID- 16619923
TI  - Undermining self-efficacy: the consequence of nurse unfriendliness on client
      wellbeing.
AB  - Although unfriendly nurse behaviours are noted in research findings, no study
      names these behaviours as such, nor investigates the impact of nurse
      unfriendliness on clients. Because the present findings reveal the phenomenon of
      nurse unfriendliness, they allow both the phenomenon and its consequences to be
      understood. These findings were developed through secondary data analysis of a
      text where participants discussed their encounters, during hospitalisation/s in
      2002-2003, with friendly and unfriendly nurses. Findings reveal nurse
      unfriendliness is characterised by frostiness, officiousness and apathy. It
      results in thoughtless and inept nursing and in a hostile environment where
      clients feel unsafe, unwelcome and unaided. Unfriendly nurses create barriers-
      they are disrespectful, cheerless, unresponsive and domineering so clients feel
      belittled, disheartened, unprotected and distressed. When clients are placed in
      this position, their self-efficacy is undermined. By revealing the consequences
      of nurse unfriendliness on client wellbeing, findings from this study advance
      nursing knowledge.

PMID- 16619924
TI  - Dishing the drugs: a qualitative study to explore paediatric nurses' attitudes
      and practice related to medication administration.
AB  - AIMS: The objectives of this study were to identify nurses' attitudes toward
      medication policies and the perceived factors that influence nurses' adherence to
      the medication policy or their ability to follow policy in the clinical
      environment of a tertiary paediatric hospital. METHODS: Using a focus group
      methodology, data were collated from a group of 32 nurses working in eight
      clinical areas of a tertiary paediatric hospital. Each discussion was transcribed
      and the data were subjected to a qualitatively based content analysis.
      RESULTS/FINDINGS: Four main categories emerged from the data including
      accessibility of information, time constraints, practice issues and professional
      conflict. CONCLUSIONS: Medication administration is a complex area of paediatric
      nursing practice. In an innovative attempt to assist in understanding nursing
      medication practice, this research has directly obtained nurses' perceptions of
      the factors that may influence their adherence to medication policy in the
      clinical environment. These results will inform future risk management strategies
      related to nursing medication practice.

PMID- 16619925
TI  - Use and development of clinical pathways by registered nurses in an acute
      paediatric setting.
AB  - Clinical pathways are widely regarded as providing valuable knowledge about
      specific types of patients and their care, as well as providing direct guidance
      in clinical practice. In Australia, the use of care pathways has occurred with
      seemingly minimal professional nursing debate as to their benefits in practice.
      Comments supporting the introduction of pathways into clinical practice have
      focused on assistance to decision making, facilitation of clinical judgements
      about care, assistance in improving practice and utility as educational tools,
      particularly for new staff, new graduates and casual employees. A survey of 259
      nurses working in an acute paediatric setting sought to gain their views about
      pathways of care with regard to satisfaction with use, content of pathway,
      ability to use in practice, effect on practice and commitment to use. While the
      most positive findings to emerge from the research indicated that nurses liked
      clinical pathways because they saved time and reduced documentation requirements,
      issues were also raised about the need for a broader, more inclusive development
      process for pathways, and an improved education program for staff use. The
      implications to arise from these findings are important for senior staff and
      educators who are responsible for staff orientation programs and ongoing staff
      development as well as for those responsible for the development and
      implementation of clinical pathways into practice.

PMID- 16619926
TI  - The body electric: a review of literature on implantable cardioverter
      defibrillators.
AB  - The number of scientific research studies expounding the efficacy and
      effectiveness of the implantable cardioverter defibrillator (ICD) in the
      treatment of cardiac arrhythmias and the prevention of sudden cardiac death (SCD)
      is prolific. The results from clinical trials that have led to the acceptance of
      implanting the human heart with an ICD are not as convincing as medical science
      would have health-care consumers believe. There are many other scientific studies
      that deal with the hazards involved in heart implantation with an ICD. It is
      argued in this paper that the impact of heart implantation with an ICD is
      hazardous to a person's being in significant ways. Heart implantation with an ICD
      is hazardous to physiological wellbeing, to psychosocial wellbeing, and to
      quality-of-life wellbeing. It is also argued that although humanistic studies are
      beginning to filter through the maze of scientific studies, many gaps remain in
      ICD research. Scientific researchers agree that there remains much needed
      knowledge for cardiac patients, their family members, and for health
      professionals.

PMID- 16619927
TI  - Postmodern pedagogy and the nursing curriculum: collaborating for excellence.
AB  - Nursing in developed and developing countries alike has made, or is making, the
      move from apprenticeship and service-driven models of nurse education to those
      situated in and determined by the higher education sector. In Australia this move
      was made some twenty years ago. In this paper I present the epistemological and
      operational contours of a highly successful collaboration between the Tasmanian
      School of Nursing & Midwifery and St Vincent's Private Hospital, Sydney. In
      educational terms this collaborative curriculum is forged from a postmodern
      pedagogy. This means both student and teacher become reciprocal agents in the
      making of (new) knowledge arising out of a praxis-oriented curriculum whereby
      theory informs practice and practice mutually informs theory. Both the university
      and the hospital are significant beneficiaries of this professional/business
      partnership and as a result, the oft discussed 'theory/practice divide' is
      thwarted in its conceptualisation and articulation through the ways the
      university (theory) and the hospital (practice) amalgamate through their combined
      responsibility for the students' success.

PMID- 16619928
TI  - What price petrol?

PMID- 16619929
TI  - The weighty issue of Australian television food advertising and childhood
      obesity.
AB  - ISSUE ADDRESSED: The aim of this paper is to provide an accessible overview of
      research literature on the link between childhood obesity and food advertising on
      Australian television. METHODS: A systematic review of current medical, public
      health, psychological and marketing research literature surrounding the topics of
      childhood obesity and television food advertising, with emphasis on Australian
      data. RESULTS: Childhood obesity rates have tripled since 1985, mirrored by
      increases in consumption of energy-dense foods. Energy-dense food advertising is
      ubiquitous in children's television programming, but children's ability to
      perceive the commercial intent of advertisements only emerges gradually as a
      function of age. Until such time, children are trusting, and hence vulnerable, to
      food advertising, influencing their desires and purchase requests to parents.
      There is robust evidence to suggest that television viewing and childhood obesity
      are related. However, the direction of causation and specific contribution of
      food advertising remains equivocal. Moreover, the link between television and
      childhood obesity is surprisingly weak, with only a small independent effect size
      (approximately 1%). CONCLUSIONS: Television food advertising seems to have only a
      very small, indirect link to childhood obesity.

PMID- 16619930
TI  - 'Make a move' falls prevention project: an area health service collaboration.
AB  - ISSUE ADDRESSED: Since a lack of physical activity is a risk factor for falling,
      effective interventions to increase participation rates among older people need
      to be found. This project assessed the viability of a metropolitan Area Health
      Service collaboration to increase physical activity rates among older people.
      METHODS: A collaboration involving six Area Health Services in the Sydney
      metropolitan area, central coast of New South Wales (NSW), and NSW Department of
      Health was established. Interventions included a communication strategy to raise
      awareness of the benefits of physical activity for preventing falls and
      enhancement of local physical activity programs for older people. A repeated
      measures cross-sectional design was used to assess increases in physical activity
      programs and older people's participation, and data of fall-related hospital
      admissions were examined. Annual activity logs were completed to track local
      project activities. Semi-structured interviews with key stakeholders and
      workshops were used to review the collaborative management model. RESULTS:
      Response to the communication strategy and gains in physical activity programs
      for older people varied among Area Health Services. Overall, approximately 2,929
      people called the campaign inquiry hotlines in response to the media campaign,
      Area Health Service-supported exercise programs for older people increased by
      19%, participation rates increased by 16%, and fall-related hospital admissions
      were observed to plateau. The collaborative management model used was somewhat
      effective, but had difficulties for the issue being addressed. CONCLUSION: 'Make
      a Move' added value to local physical activity programs for older people and
      increased the number of older people participating in Area Health Service
      supported exercise programs. Collaborative projects are worthwhile if they
      address the right issue, involve the right partners and have sound management
      processes.

PMID- 16619931
TI  - Improvement in asthma management practices in child care services: an evaluation
      of a staff education program.
AB  - ISSUES ADDRESSED: The aim of this study was to identify the strengths and
      weaknesses of asthma management in child care services in the Hunter region and
      to develop, implement and evaluate a health education program to address the
      deficiencies. METHODS: A questionnaire was sent to the 190 child care services in
      the Hunter region in 1997 to assess their asthma management practices. Results of
      the survey were used to develop a two-hour training workshop for child care staff
      in the management of asthma. District-based workshops were conducted for 535
      child care staff (representing 140 services) over two years. Participants
      completed pre- and post-workshop knowledge and confidence questionnaires. The
      survey was repeated in 2000. RESULTS: The baseline survey identified potential
      for substantial improvement in the management of asthma in child care services
      and in the training of staff. Training workshops significantly improved asthma
      knowledge and confidence in managing asthma (p<0.0001). The follow-up survey
      showed that an additional 50% (p<0.0001) of all child care services had
      implemented recommended asthma management practices. CONCLUSION: The program was
      effective in achieving vast improvements in the knowledge and confidence that
      child care staff require to manage asthma and has led to the broad dissemination
      and adoption of the appropriate policies and procedures for the management of
      asthma in child care services.

PMID- 16619932
TI  - Playing the game on the World Wide Web.
AB  - ISSUE ADDRESSED: 'Celebrate - do it Safely' is a project aimed at reducing youth
      alcohol-related harm on the Central Coast, New South Wales (NSW). The primary
      focus for 2003 was to use the world wide web and the website
      www.celebratesafely.com.au to raise awareness and reinforce the message of how to
      party safely to young people. METHODS: A creative, interactive website was set up
      to be a local and reliable source of information regarding the risks associated
      with alcohol misuse. It was supported by a steering committee with diverse
      representation from key organisations. Content pages and links were developed to
      ensure access to information and contact details were simple and comprehensive.
      Topics such as a safe party checklist, safe driving, safe sex and protection from
      violence were included. Games and competitions emphasised the safe party message
      with clever actions and graphics created within a virtual party environment. The
      website was promoted by distribution of postcards throughout the school network.
      Radio campaigning, plus display of posters and banners throughout the area,
      raised the profile in the wider community. Key rings were given to young people
      along with free 'mocktails' to reinforce the message of safe partying. RESULTS:
      There has been an increase in website hits from 758 in 2002 to more than 65,000
      in 2003. Written feedback from young people suggests the content and format is
      well designed for the target group. CONCLUSIONS: Promoting the message of safe
      celebration on the world wide web is an effective way of raising awareness in a
      local community about safe partying.

PMID- 16619933
TI  - Quantitative methods used in Australian health promotion research: a review of
      publications from 1992-2002.
AB  - ISSUE ADDRESSED: This study examined the use of quantitative methods in
      Australian health promotion research in order to identify methodological trends
      and priorities for strengthening the evidence base for health promotion. METHODS:
      Australian health promotion articles were identified by hand searching
      publications from 1992-2002 in six journals: Health Promotion Journal of
      Australia, Australian and New Zealand journal of Public Health, Health Promotion
      International, Health Education Research, Health Education and Behavior and the
      American Journal of Health Promotion. The study designs and statistical methods
      used in articles presenting quantitative research were recorded. RESULTS: 591
      (57.7%) of the 1,025 articles used quantitative methods. Cross-sectional designs
      were used in the majority (54.3%) of studies with pre- and post-test (14.6%) and
      post-test only (9.5%) the next most common designs. Bivariate statistical methods
      were used in 45.9% of papers, multivariate methods in 27.1% and simple numbers
      and proportions in 25.4%. Few studies used higher-level statistical techniques.
      CONCLUSIONS: While most studies used quantitative methods, the majority were
      descriptive in nature. The study designs and statistical methods used provided
      limited scope for demonstrating intervention effects or understanding the
      determinants of change.

PMID- 16619934
TI  - Backyard swimming pool safety inspections: a comparison of management approaches
      and compliance levels in three local government areas in NSW.
AB  - ISSUE ADDRESSED: Since 1992, swimming pool fencing has been a legislative
      requirement in New South Wales (NSW), yet compliance with the NSW Swimming Pool
      Act is mixed. Local councils are responsible for the enforcement of the act.
      However, their approach to enforcement and the management of backyard swimming
      pool safety inspections is varied. METHODS: A random sample of backyard swimming
      pools was inspected in Council A and existing compliance data for pools in two
      other councils (B and C) were obtained. Pool owners in Council A were surveyed
      regarding their attitudes to pool fencing and inspections. Semi-structured
      interviews were conducted with council employees. RESULTS: Pool compliance rates
      across the three council areas varied. In Councils A and C, 51% and 54% of pools,
      respectively, were found to be non-compliant at the first inspection. Following
      re-inspection in Council A of 227 pools, a further 125 pools reached compliance.
      In Council B, 97% of the inspected pools were compliant. CONCLUSIONS: This study
      provides evidence of poor backyard swimming pool safety compliance where local
      government inspection activity is minimal or non-existent.

PMID- 16619935
TI  - Demographic and individual correlates of achieving 10,000 steps/day: use of
      pedometers in a population-based study.
AB  - ISSUES ADDRESSED: The 10,000 steps per day message has become popular, yet few
      studies have examined correlates associated with achieving this behaviour target.
      This paper examines demographic and individual factors associated with adults
      achieving 10,000 steps/day. METHOD: Participants in a state-wide, cross-sectional
      physical activity survey were invited to take part in a pedometer study (n=603,
      45% response rate). A pedometer was worn for one week and daily steps recorded in
      a diary. Participants providing four or more days of pedometer data (n=428) were
      dichotomised based on achievement of > or =10,000 steps/day. RESULTS: Men
      performed significantly more daily steps than women on average (10,079+/-3,848
      and 9,169+/-3,800, p=0.01). In males, those less likely to achieve > or =10,000
      steps/day were > or =60 years of age (OR=0.21) and overweight (i.e. body mass
      index > or =25kgm2) (OR=0.40), while men who regularly walked in the workplace
      (OR=1.44), who did vigorous activity at work (OR= 3.75), or who were employed in
      a blue-collar occupation (OR=4.45) were more likely to report reaching this
      target. In women, being overweight (OR=0.55) was negatively associated with
      achieving > or =10,000 steps/day, while participating in > or =150 minutes of
      leisure-time physical activity/week (OR=2.26) was positively associated with
      reaching this target. CONCLUSION: Workplace physical activity and working in blue
      collar occupations contributes to the achievement of 10,000 steps/day in males.
      People who achieve current national physical activity guidelines also achieve
      10,000 steps/day. Older adults and those overweight are less likely to achieve
      this behaviour target.

PMID- 16619936
TI  - Simplifying data collection for process evaluation of community coalition
      activities--an electronic web-based application.
AB  - ISSUE ADDRESSED: It is important to document and measure coalition-based program
      activities in order to analyse and evaluate the process of program
      implementation. This paper describes the development and implementation of an
      electronic, web-based application to simplify data collection for this research
      process. METHODS: Childhood injury prevention project officers collaborated with
      injury prevention researchers to adapt a process log monitoring system initially
      developed by the Centers for Disease Control and Prevention to track coalition
      activities for evaluating community efforts to prevent cardiovascular disease.
      The adapted process log was converted into an electronic, web-based application
      that project officers completed daily. RESULTS: The web-based electronic log
      proved to be a practical tool that not only simplified the documentation and
      reporting processes for health professionals involved in the program, but also
      provided a rich source of data for subsequent comprehensive analysis of project
      implementation. CONCLUSION: Development, implementation and evaluation of this
      web-based process log, to the best of our knowledge, is the only program of its
      kind in use and provides a simple data collection solution for practitioners,
      policy makers and researchers involved in injury prevention programs and other
      community-based programs throughout the world.

PMID- 16619937
TI  - Quit smoking behaviours and intentions and hard-core smoking in New South Wales.
AB  - ISSUE ADDRESSED: Quitting intentions and behaviours of smokers require
      monitoring. In particular, assessment of the distribution of smokers on the
      quitting continuum and of the proportion of hard-core smokers has implications
      for the design of future quit campaigns. METHODS: Cross-sectional survey of 1,509
      persons (74.4% consent rate) randomly selected from the New South Wales
      Electronic White Pages. 1,431 respondents were eligible (aged 18 and over).
      RESULTS: Current smokers comprised 19.1% (n=274) and former smokers 28.0%
      (n=400). Sixty-one per cent of current smokers had quit for at least one day in
      the last year and 67.1% were in the intermediate or advanced preparation levels
      of the quitting continuum. Half of the smokers (46.7%) recalled receiving
      cessation advice during a past-year medical visit. Sixty-four point five per cent
      (64.5%) of smokers and 63.4% of former smokers reported no use of assistance in
      their quit attempts. Five point five per cent (5.5%) of smokers aged 26 and over
      met the hard-core criteria. CONCLUSION: Most smokers want to quit but when making
      a quit attempt do not use proven, effective strategies. Relapse rates are high in
      the immediate post-cessation period.

PMID- 16619938
TI  - A framework for evaluating health promotion programs.
AB  - Evaluation of health promotion interventions is essential in order to collect
      evidence about the efficacy of a program, identify ways to improve practice,
      justify the use of resources, and identify unexpected outcomes. This paper
      clarifies the role of evaluation as a crucial component of health promotion
      interventions. Moreover, it summarises the key elements of the most widely used
      planning/evaluation frameworks necessary for constructive evaluations of health
      promotion interventions and incorporates them into a single approach. It provides
      a methodical framework for the provision of evaluation guidance to health
      promotion practitioners and discusses the importance of including evaluation when
      planning any health promotion intervention. The focus of this paper is on the
      essential elements of the evaluation of health promotion programs.

PMID- 16619939
TI  - Management of brain injury in non-elite field hockey and Australian football--a
      qualitative study.
AB  - ISSUE ADDRESSED: This study aimed to assess the current understanding of brain
      injury in sport and to identify existing management and return-to-play guidelines
      associated with mild traumatic brain injury (mTBI) in non-elite field hockey and
      Australian Rules football in Western Australia. METHODS: In-depth interviews were
      conducted with key injury management personnel in non-elite field hockey and
      Australian football in Western Australia. RESULTS: None of the 20 clubs surveyed
      followed a standardised procedure for the management of head and brain injury in
      their team or sport. CONCLUSIONS: Findings from the study indicate that the
      management of head and brain injury was variable, subjective in nature, and that
      there were no evidence-based guidelines available for the management of mTBI to
      any of the respondents in this study.

PMID- 16619940
TI  - Correlates of hepatitis C testing among heroin injectors in Sydney.
AB  - ISSUE ADDRESSED: Hepatitis C infection is a significant public health problem
      with most cases occurring among injecting drug users (IDUs). Little is known
      about the uptake of testing. The study examined correlates of hepatitis C testing
      among heroin users. METHOD: Current heroin users, recruited through needle and
      syringe programs, methadone clinics and via snowballing, were interviewed about
      hepatitis C testing. RESULTS: Four hundred heroin users were interviewed and most
      (91%) reported having been tested for hepatitis C. Females and those with a
      history of incarceration or drug treatment were more likely to have been tested,
      but those who had been using for two years or less were not. CONCLUSIONS:
      Hepatitis C testing is common among heroin users. Groups most at risk of
      infection are being tested.

PMID- 16619941
TI  - Methodological issues in the psychology of religion: toward another paradigm?
AB  - Recent evaluations have identified the psychology of religion as a field in
      crisis and have called for a new multilevel interdisciplinary paradigm. However,
      a critical meta-perspective on methods reveals a broad range of methodologies,
      each appropriate for particular levels of complexity in the psychology of
      religion. No single methodology is appropriate for every level, nor can higher
      levels of complexity be explained by data from lower levels. The authors identify
      the different types of research practiced in the psychology of religion and
      critically discuss philosophical presuppositions involved in two major
      methodological traditions, the empiricist-analytical and the hermeneutical, often
      identified as quantitative and qualitative traditions, respectively.

PMID- 16619942
TI  - Factors associated with college student intent to engage in community service.
AB  - Many universities in the United States highlight service as an integral component
      to their mission. Additionally, a growing pedagogical focus highlights the
      importance of community service as an integral component of student development.
      The current study was an investigation of the factors associated with college
      student intentions to engage in volunteer community service. University students
      (N = 403) at a comprehensive university located in the southern plains completed
      an anonymous Web-based questionnaire to assess community service attitudes and
      intentions. Subsequent to testing for statistical assumptions, results from
      multiple regression analysis suggest that a sense of community connectedness,
      cost and benefit considerations, and the seriousness of community needs are
      significant variables in explaining variance in the intent to engage in community
      service.

PMID- 16619943
TI  - Gender, alcohol consumption, and parental monitoring.
AB  - The authors examined the relationships among gender, alcohol consumption, and
      parental monitoring, including television monitoring. Student volunteers (N =
      150; 90% Caucasian, 79% women) participated by reporting retrospective general
      parental monitoring, television monitoring, and recent drinking behaviors. On the
      basis of the retrospective reports by the participants, when they were growing up
      the men received less overall parental monitoring but not less television
      monitoring than the women. Women's drinking quantity was correlated with parental
      monitoring, whereas men's drinking frequency was associated with both parental
      monitoring and television monitoring. Interestingly, men's binge drinking
      frequency was correlated with television monitoring but not with overall parental
      monitoring, whereas women's binge drinking frequency was correlated with overall
      parental monitoring but not with television monitoring. Implications for
      preventing alcohol misuse and ideas for future research are discussed.

PMID- 16619944
TI  - The assessment of factorial invariance in need for cognition using Hispanic and
      Anglo samples.
AB  - The Need for Cognition Scale-Short Form (NCS-SF; J. T. Cacioppo, R. E. Petty, &
      C. F. Kao, 1984) is a commonly administered measure in the behavioral sciences,
      but little research has assessed its applicability across cultures. A sample of
      undergraduates in the southeastern United States and a sample of undergraduates
      at a southwestern U.S. university completed the NCS-SE Hispanic respondents did
      not differ from Anglos in their mean NCS-SF scores. Confirmatory factor analysis
      revealed that factor parameter estimates and item intercepts were partially
      measurement invariant across samples.

PMID- 16619945
TI  - Depression proneness and reactions to a depressive stimulus.
AB  - In the context of a project examining depression vulnerability and cigarette
      smoking, the authors tested whether depression-vulnerable people differed from
      less vulnerable people in their reactions to a depressive stimulus. Regular
      smokers with a history of depression but not currently depressed (n = 63) and
      never-depressed smokers (n = 64) listened to audiotapes of confederates reading
      depressive and nondepressive scripts and reported their reactions. Neither a
      history of depression nor self-reported depression proneness predicted reactions
      to depression. However, depression proneness was positively correlated with
      beliefs about depression contagion. Likewise, stronger depression-related
      contagion beliefs and lower levels of empathic responding predicted behavioral
      rejection of the depressive stimulus.

PMID- 16619946
TI  - Bayes Window (3): where do prior probabilities come from?

PMID- 16619947
TI  - Testing the coplanar ratio hypothesis of lightness perception.
AB  - What determines an object's lightness remains unclear, but it is generally
      thought that the ratios of its luminance to the luminance of other objects in a
      scene play a crucial role because these ratios allow the relative reflectance of
      each object to be estimated, providing all the objects are under the same
      illumination. Because objects that lie in the same plane are typically
      illuminated equally, it has been suggested that it is the luminance ratios
      between coplanar objects that primarily determine lightness (Gilchrist, 1977
      Science 195 185-187; Gilchrist et al, 1999 Psychological Review 106 795-834). An
      alternative hypothesis is that perceived illumination differences can affect
      lightness directly. As the studies that provided evidence for the coplanar ratio
      hypothesis always varied the illumination and the coplanar relationships
      simultaneously, it is unclear which hypothesis is correct. I measured the
      influence of each factor separately and found that the perceived illumination
      differences have a greater effect on lightness.

PMID- 16619948
TI  - The control of fixation duration in visual search.
AB  - A study is reported how fixation durations are affected as observers voluntarily
      use information in the visual environment to direct saccades in search of a
      target. In experiments with direction-coded displays, search fixation durations
      for correct and incorrectly directed saccades were comparable during image
      driven/bottom-up search. In contrast, for knowledge-driven search, the
      relationship depended on peripheral preview. With ample access to peripheral
      preview, search fixation durations preceding correct saccades were shorter than
      those preceding incorrectly directed saccades. However, they were longer when
      preview was constrained by a gaze-contingent moving window. Fixation control was
      modeled as sigmoid functions.

PMID- 16619949
TI  - Perceiving patterns of play in dynamic sport tasks: investigating the essential
      information underlying skilled performance.
AB  - The perceptual-cognitive information used to support pattern-recognition skill in
      soccer was examined. In experiment 1, skilled players were quicker and more
      accurate than less-skilled players at recognising familiar and unfamiliar soccer
      action sequences presented on film. In experiment 2, these action sequences were
      converted into point-light displays, with superficial display features removed
      and the positions of players and the relational information between them made
      more salient. Skilled players were more accurate than less-skilled players in
      recognising sequences presented in point-light form, implying that each pattern
      of play can be defined by the unique relations between players. In experiment 3,
      various offensive and defensive players were occluded for the duration of each
      trial in an attempt to identify the most important sources of information
      underpinning successful performance. A decrease in response accuracy was observed
      under occluded compared with non-occluded conditions and the expertise effect was
      no longer observed. The relational information between certain key players, team
      mates and their defensive counterparts may provide the essential information for
      effective pattern-recognition skill in soccer. Structural feature analysis,
      temporal phase relations, and knowledge-based information are effectively
      integrated to facilitate pattern recognition in dynamic sport tasks.

PMID- 16619950
TI  - Does the use of natural stimuli facilitate amodal completion in pigeons?
AB  - Three experiments were carried out to investigate whether amodal completion in
      pigeons can be facilitated by the use of colour photographs instead of highly
      artificial stimuli such as geometrical shapes. Ten pigeons were trained in a
      go/no-go procedure to discriminate between photographs of complete and of
      incomplete pigeon figures. In the subsequent test, the birds classified pictures
      of partly occluded pigeons as though they were complete (experiment 1). However,
      we found evidence that classification was based on spurious stimulus features
      that paralleled the intended class rule of figural completeness versus
      incompleteness. In particular, classification was shown to be guided by white
      background gaps that separated the parts of the fragmented pigeon figures
      (experiment 2), as well as by cues related to overall Gestalt (experiment 3). In
      summary, the present results indicate that the use of more natural stimuli such
      as photographs instead of geometrical shapes is insufficient for providing amodal
      completion in pigeons. It is suggested that a combination of various cues,
      including, eg, 3-D information and common motion in addition to surface and
      contour properties, may be required to induce a perceptual bias favouring visual
      completion of occluded portions.

PMID- 16619951
TI  - Visual motion interferes with tactile motion perception.
AB  - Previous studies have demonstrated that visual apparent motion can alter the
      judgment of auditory apparent motion. We investigated the effect of visual
      apparent motion on judgments of the direction of tactile apparent motion. When
      visual motion was presented at the same time as, but in a direction opposite to,
      tactile motion, accuracy in judging the direction of tactile apparent motion was
      substantially reduced. This reduction in performance is referred to as 'the
      congruency effect'. Similar effects were observed when the visual display was
      placed either near to the tactile display or at some distance from the tactile
      display (experiment 1). In experiment 2, the relative alignment between the
      visual and tactile directions of motion was varied. The size of the congruency
      effect was similar at 0 degrees and 45 degrees alignments but much reduced at a
      90 degrees alignment. In experiment 3, subjects made confidence ratings of their
      judgments of the direction of the tactile motion. The results indicated that the
      congruency effect was not due to subjects being unsure of the direction of motion
      and being forced to guess. In experiment 4, static visual stimuli were shown to
      have no effect on the judgments of direction of the tactile stimuli. The extent
      to which the congruency effect reflects capture effects and is the result of
      perceptual versus post-perceptual processes is discussed.

PMID- 16619952
TI  - Are people with high and low mental rotation abilities differently susceptible to
      the alignment effect?
AB  - We investigated whether the alignment effect (Levine et al, 1982 Journal of
      Experimental Psychology: General 111 157-175) is influenced by mental rotation
      abilities. In two experiments, groups of undergraduate students with high and low
      performance in mental rotation tasks were required to study either schematic
      (experiment 1) or more complex (experiment 2) maps, and to perform a number of
      pointing tasks adopting a perspective which could be aligned, misaligned (45
      degrees, 135 degrees), or counteraligned (180 degrees) with the perspective
      assumed during learning. Cognitive styles in spatial representation have also
      been considered. Results of experiment 1 show that people with low performance in
      mental rotation tasks prefer to adopt a representation of space focused more on
      landmarks. Their performance in the pointing tasks depends on the alignment
      conditions, with more errors in the counteraligned condition followed by the two
      misaligned and aligned ones. In contrast to this, high-ability mental rotators
      prefer survey and route spatial representations and are affected only by the
      aligned and non-aligned conditions. In the second experiment, practice was
      studied as a function of mental rotation and alignment. The group high in mental
      rotation ability was found to be free from the alignment effect in the pointing
      tasks performed after the final of four learning phases.

PMID- 16619953
TI  - Perceiving causality after the fact: postdiction in the temporal dynamics of
      causal perception.
AB  - In simple dynamic events we can easily perceive not only motion, but also higher
      level properties such as causality, as when we see one object collide with
      another. Several researchers have suggested that such causal perception is an
      automatic and stimulus-driven process, sensitive only to particular sorts of
      visual information, and a major research project has been to uncover the nature
      of these visual cues. Here, rather than investigating what information affects
      causal perception, we instead explore the temporal dynamics of when certain types
      of information are used. Surprisingly, we find that certain visual events can
      determine whether we perceive a collision in an ambiguous situation even when
      those events occur after the moment of potential 'impact' in the putative
      collision has already passed. This illustrates a type of postdictive perception:
      our conscious perception of the world is not an instantaneous moment-by-moment
      construction, but rather is formed by integrating information presented within
      short temporal windows, so that new information which is obtained can influence
      the immediate past in our conscious awareness. Such effects have been previously
      demonstrated for low-level motion phenomena, but the present results demonstrate
      that postdictive processes can influence higher-level event perception. These
      findings help to characterize not only the 'rules' of causal perception, but also
      the temporal dynamics of how and when those rules operate.

PMID- 16619954
TI  - Orientation misperceptions induced by contrast polarity: comment on "Contrast
      polarities determine the direction of Cafe Wall tilts" by Akiyoshi Kitaoka,
      Baingio Pinna, and Gavin Brelstaff (2004).
AB  - According to Kitaoka et al (2004, Perception 33 11-20), the Cafe Wall illusion
      can be reduced to misalignment effects produced locally by a large shape on a
      line passing nearby. I demonstrate here that the interacting units are edges and
      not whole shapes, and that the source of the illusion does not consist in a local
      tilt but in a tendency of the edges to join when they have the same contrast
      polarity.

PMID- 16619955
TI  - The Mona Lisa effect: is 'our' Lisa fame or fake?
AB  - This demonstration uses one of the most famous human faces, the portrait of Mona
      Lisa, La Gioconda, by Leonardo da Vinci. Usually, we have a very accurate and
      stable representation of the exact configuration of such a familiar face.
      Typically, we are able to rapidly recognise even subtle configural changes.
      However, here we show that an exposure to specific alterations performed on a
      familiar face substantially reduces this ability even over a time period as long
      as 80 min. This demonstration illustrates the flexibility of the perceptual
      system and adaptation to new information.

PMID- 16619956
TI  - [Treatment of dyslipidemia in clinical practice].
AB  - The incidence of dyslipidemia is rising worldwide. Dyslipidemia combined with
      other factors represent the primary risk factors for the development of
      cardiovascular diseases. The National Cholesterol Education Program has recently
      updated the Adult Treatment Panel III guidelines and called for more intensive
      lipid lowering treatment, especially in patients at high risk for coronary heart
      disease. A statin and fibrate combination is a possible approach, moreover,
      niacin, particularly in combination with statins, might have a successful
      comeback. However, despite the existence of evidence-based treatment guidelines
      and effective antilipemic medications, recommended cardiovascular risk reduction
      rarely is achieved. This article summarises the mechanisms of action of available
      lipid lowering agents, their recommended dosing regiments and possible drug
      interactions.

PMID- 16619957
TI  - [Bronchoscopic lung volume reduction surgery in emphysema].
AB  - Despite of the clinical studies proving the benefits of lung volume reduction
      surgery and determining the indications and candidates, the surgical intervention
      has not penetrated into the standard treatment of emphysema. Perioperative
      mortality is relatively high at patients with end-stage emphysema, therefore a
      less invasive procedure might be most useful in medical practice. Bronchoscopic
      lung volume reduction is a technically simple procedure including insertion of a
      bronchial blocker (plug) or an endobronchial valve, either totally blocking the
      air flow, or blocking it only during the inspiration. However, there are only few
      clinical data available concerning of surgical and bronchial interventions. A
      multinational clinical study is in progress in three Hungarian pulmonological
      centers implanting endobronchial plugs into the subsegmental bronchi of patients
      with severe emphysema.

PMID- 16619958
TI  - [Breast Center--a virtual unit for the multidisciplinary care of breast
      patients].
AB  - Breast cancer, the most prevalent female malignancy represents a major health
      problem. Breast cancer mortality may be halved by high quality mammography
      screening and care. The most efficient screening and the best treatment of
      patients are available at the breast centers that are equipped with special
      facilities, expertise and significant experience via the treatment of a high
      number of patients. Breast center is a virtual unit based on the collaboration of
      various professionals; a tight institutional frame is not a must. In these
      comprehensive centers, 150 breast cancer patients per year at a minimum are
      treated, and the most efficient special treatment methods are available. The core
      members of the staff are the breast pathologists, the mammographists, the breast
      surgeons, the oncologists/oncoradiologists, the breast nurses, the technicians
      and the data managers. An easy access to the service of the non-core members, the
      plastic surgeons, the psychologists, the psychiatrists and the clinical
      geneticists is necessary. An optimal collaboration of the various experts may be
      achieved by a training of the members, regular multidisciplinary meetings and
      guidelines developed and accepted by all. The requirements of a breast center
      have been published by the European Society of Mastology (EUSOMA), and a
      directory of the accredited European breast centers is maintained. The Breast
      Unit of the University of Szeged has been found eligible by EUSOMA to be included
      in the directory of the European breast units. Two mammographists do screening
      mammography and clinical examination, 2 pathologists perform cytopathological,
      histopathological and immunohistochemical examinations. Three surgeons operate on
      more than 250 breast cancer patients per year, and apply wire or isotope (ROLL)
      localisation in case of non-palpable lesion. A plastic surgeon is available if
      necessary. In a half of all cases, sentinel mapping is performed with isotope-
      and blue dye-labelling. Two radiotherapists apply conformal radiotherapy in 250
      cases per year, and 2 oncologists perform modern chemotherapies in 200 cases as a
      yearly average; 50 new advanced/metastatic cases per year require oncological
      treatments. Breast nurses, a psycho-oncologist and a mental hygienist nurse
      assist the team. There is access to lymphedema treatment and physiotherapy. The
      final goal of the program is to provide all women with high quality mammography
      screening and care, if necessary.

PMID- 16619960
TI  - [A cross sectional study of titanium plates surface-treated with anodic
      oxidation].
AB  - It is an important modern trend to try to modify the surface properties of
      titanium implants with titanium oxide produced in various ways. One possibility
      of surface modification is the formation of an oxide layer by heat and electric
      treatment. The authors examined three osteosynthesis plates treated with anodic
      oxidation of Hungarian development. 5-10 microm thick slides were made of the
      plates in several cross sectional planes with a special cutting-grinding
      technique and were examined under a microscope with various magnifications. In
      the study it was seen that the surface of the basic metal was covered with a
      continuous oxide layer in all the cross sectional planes. No material faults were
      discovered on the surface. The thickness of the surface layer in various regions
      was found to be changing in the nm range, which coincides with the results of
      other studies. It was proven in the study by using the surface modification
      technique in part developed by the authors a passivating layer was formed on the
      surface of titanium, which separates it from the human organism.

PMID- 16619959
TI  - [The modern treatment of colorectal cancer. Present and future].
AB  - The modern treatment of colorectal cancer. Present and future. Fluorouracyl has
      been the mainstay of treatment for colorectal cancer for decades. The addition of
      folinic acid to 5FU, the use of infusional, rather than bolus 5FU, and the
      combination of new active agents such as irinotecan and oxaliplatin with 5FU/LV
      have each led to increase in effectivity. Oral formulations of fluoropyrimidines
      can replace the infusional 5FU therapy with better convenience. The authors
      review the current progress with the use of novel molecular targeted therapies
      that are tumor specific with better toxicity profile than chemotherapy. The
      integration of the new biological response modifier therapeutic possibilities in
      the chemotherapy protocols may result prolongation in survival, in metastatic
      patients the presently 2 years survival will approach 3 years. Combining these
      drugs with chemotherapeutics in the adjuvant setting we hope to raise further the
      presently achieved 78% of 3 years disease free survival by oxaliplatin plus 5FU
      therapy. As the variation of agents has been increased, choosing the most
      effective treatment strategy has become increasingly complex.

PMID- 16619961
TI  - [Investigation of visceral hyperesthesia in irritable bowel syndrome].
AB  - BACKGROUND: It has been well established that visceral hyperesthesia plays a role
      in the development of irritable bowel syndrome (IBS). AIMS: 1. to detect the
      possible changes of visceral perception in different subtypes of IBS patients, 2.
      to analyze the difference of visceral hyperaesthesia in different subtypes of
      IBS, 3. to examine whether distension protocols (e.g. phasic or ramp distension)
      has any influence on sensory thresholds, 4. to analyze the differences of
      perception thresholds produced by phasic or ramp distension in different subtypes
      of IBS. METHODS: 10 patients having colorectal polypectomy (control group) and 40
      IBS patients were studied. The diagnosis was based on the Rome-II criteria.
      Diarrhoea-predominant, alternating and constipation-predominant subtypes were
      determined by the Talley bowel habit questionnaire. Sensory thresholds were
      detected by semi random ascending phasic and ramp rectosigmoid distension. Rectal
      dynamic compliance was calculated by using the dV/dP ratio. RESULTS: 1. The pain
      thresholds determined by phasic distension were significantly lower in all
      subtypes of IBS. 2. Increased thresholds for pain were found in almost half of
      constipation-predominant IBS patient determined by ramp distension. Thus two
      distinct subgroups could be found based on the findings of ramp distension: a
      normosensitive and a hyposensitive group. 3. Rectal dynamic compliance was
      significantly higher both in the constipation-predominant and alternating subtype
      of IBS patients. CONCLUSION: Visceral hyperesthesia can be detected in all types
      of IBS. Tolerance to physiologic stimuli could be observed in constipating IBS
      patients that is not related to the increase of rectal compliance.

PMID- 16619962
TI  - Science versus (some people's) religion.

PMID- 16619963
TI  - What was the "take home" Sunday school lesson revisited by Dr. Abel?

PMID- 16619964
TI  - "Intelligent design" movement.

PMID- 16619965
TI  - "Creation science".

PMID- 16619966
TI  - Professionals serving professionals: AFMC working to help hone processes, improve
      care.

PMID- 16619967
TI  - An all too frequent story.

PMID- 16619968
TI  - Saving starfish. Arkansas programs provide service to those without access to
      health care.

PMID- 16619969
TI  - Advances in pediatric gastroenterology: introducing video camera capsule
      endoscopy.
AB  - The video camera capsule endoscope is a gastrointestinal endoscope approved by
      the U.S. Food and Drug Administration in 2001 for use in diagnosing
      gastrointestinal disorders in adults. In 2003, the agency approved the device for
      use in children ages 10 and older, and the endoscope is currently in use at
      Arkansas Children's Hospital. A capsule camera, lens, battery, transmitter and
      antenna together record images of the small intestine as the endoscope makes its
      way through the bowel. The instrument is used with minimal risk to the patient
      while offering a high degree of accuracy in diagnosing small intestine disorders.

PMID- 16619970
TI  - Metabolic disease: a marriage of anatomic and biochemical pathology.

PMID- 16619971
TI  - After the hurricanes.

PMID- 16619972
TI  - NNOC/CNA breaks promises to Cook County nurses.

PMID- 16619973
TI  - ANA works to promote influenza vaccination among RNs.

PMID- 16619974
TI  - A state of emergency. Nurses continue to contend with crowded EDs.

PMID- 16619975
TI  - The look of the nursing workforce.

PMID- 16619976
TI  - The welcome wagon. Minnesota's Third District connects experienced with new
      members through ambassador-mentorship program.

PMID- 16619977
TI  - [Cardiomyopathies due to defective energy metabolism: morphological and
      functional features].
AB  - Cardiomyopathies are defined as diseases of the myocardium associated with
      cardiac dysfunction and are classified by morphological characteristics as
      hypertrophic (HCM), dilated (DCM) arrhithmogenic right ventricular (ARVC) and
      restrictive cardiomyopathy. These were once considered as specific diagnoses but
      there is now considerable evidence that many different gene mutations can cause
      these pathologies. In recent years, big emphasis has been given to the
      possibility that deregulation of cardiac metabolism may play a role in the
      mechanisms that lead to cardiac maladaptive remodelling. Cardiac energy
      metabolism is tightly controlled in mammalian organisms during development and in
      response to diverse dietary, physiologic, and pathologic conditions. The cardiac
      phenotype of many genetic diseases caused by mutations in proteins involved in
      mitochondrial energy production and/or homeostasis, underscores the importance of
      energetic pathway on cardiac function. For example, inborn errors in nuclear
      encoded mitochondrial fatty acid oxidation (FAO) pathway enzymes and defects in
      fatty acid uptake are an important cause of childhood HCM and sudden death.
      Abnormalities in mitochondrial respiratory chain function, particularly those
      caused by mitochondrial DNA (mtDNA) mutations, are responsible for a
      heterogeneous group of clinical disorders, including isolated HCM. Mitochondrial
      cardiomyopathies (MCM) are characterized by an adverse clinical course with
      biventricular dilation and failure, even at a young age. Mutations in genes
      encoding the gamma2 subunit of AMP-activated protein kinase (PRKAG2), alpha
      galactosidase A (GLA) and lysosome-associated membrane proteine-2 (LAMP2) can
      cause profound myocardial hypertrophy in association with electrophysiological
      defects. Unlike HCM due to sarcomere gene mutations, which is characterized by
      myofiber disarray and fibrosis, large cytosolic vacuoles characterize
      cardiomyopathy due to defect in energy metabolism. Ultrastructural analysis
      revealed massive mitochondrial proliferation in MCM and glycogen in complexes
      with protein and/or lipids in cardiomyopathy due to PRKAG2, GLA and LAMP2
      mutations.

PMID- 16619978
TI  - [Approach to the study of vasculitides: general aspects and classification].
AB  - Since etiology and pathogenesis of most systemic and/or isolated vasculitides are
      unknown, any attempt to make a rational classification of these entities is far
      from being perfect. Vasculitis may be a primary disease or it may be associated
      with connective tissue diseases, infectious diseases, neoplasms, drug assumption,
      allograft rejection and so on. As secondary vasculitides constitute the majority
      of cases, diagnosis of primary vasculitis is made by exclusion. At the present
      time, the 1993 Chapel Hill Consensus Conference on Nomenclature of Primary
      Vasculitides provides a useful guide to clinician and pathologist for evaluating
      a patient with an idiopathic form of vasculitis. This classification is based on
      the predominant size of vessels affected and describes the main clinico
      pathologic features of the various clearly defined types of systemic vasculitis.
      Though it suffers from omissions and contradictions, in routine practice it is of
      great help to distinguish diseases in this intriguing chapter of pathology.

PMID- 16619979
TI  - Leiomyoma of the nasal cavity. A case report.
AB  - Most of the sinonasal tumours are of epithelial origin. Smooth muscle tumours are
      extremely rare, they account for less than 2.5% of the mesenchymal neoplasms of
      the sinonasal tract and the nasopharynx. Fewer than 30 cases of primary
      leiomyogenic tumours have been reported in the sinonasal tract with almost an
      equal frequency of benign and malignant types. We report a case of a rare
      leiomyoma of the nasal cavity. The pathological and the clinical characteristics
      of this tumour are discussed.

PMID- 16619980
TI  - [Myopericytoma-type perivascular myoma located in the soft tissue of the foot: a
      case report and review of the literature].
AB  - We describe a rare case of myopericytoma-type perivascular myoma (MTPM) which
      arose in acral location and the literature on this field is briefly reviewed. The
      patient, a 68-year-old man, presented with an enlarging painful nodule, 1.4 cm
      across, located in the subcutaneous tissue of the right foot. The patient is
      alive and well 17 months after surgical excision of the nodule. Microscopically,
      the lesion was well-circumscribed and characterized by a biphasic pattern with a
      concentric perivascular spindle and ovoid cell proliferation and an extensive
      hemangiopericytomatous growth component. Immunohistochemically, the neoplastic
      cells were positive for vimentin, smooth muscle actin, desmin and calponin,
      negative for S-100 protein, CD34, CD31 and cytokeratins (AE1/AE3, Cam 5.2).
      Electron microscopy showed electrondense cell bodies suggestive for myopericytic
      differentiation. The clinico-pathological features of the present case are
      similar to those previously reported in the literature and we also discuss herein
      the main histological criteria for the differential diagnosis with other spindle
      cell and vascular lesions of soft tissues.

PMID- 16619981
TI  - ["Acute human glanders". Contribution for the scientific history of the Museum of
      pathological anatomy established in Trieste Hospital].
AB  - The Museum of Pathological Anatomy of the Regina Elena City Hospital of Trieste
      houses various pathological preparations of infective and contagious diseases,
      dating back to the early 1900's (ileo-typhus, dysentery, tuberculosis, syphillis,
      pulmonary plague, etc.) together with their relative diagnostic certificates.
      These bear witness to the key role of the Hospital's Anatomical Institute (in
      operation operating since 1872) during the height of the Pasteurian age. In fact,
      the Institute houses several anatomical-pathological preparations from a fatal
      clinical case of "acute human glanders". These preparations were correlated by
      laboratory animal experiments using Strauss' method and emblematically recall the
      eziological determinism of the new bacteriological science. The preparations
      served in their day not only as indisputable diagnostic evidence, but can now be
      considered a promotional metaphor of the scientific mission the Triestine
      Anatomical Institutes Director, Dr. Enrico Ferrarri (a disciple of Richard
      Paltauf), endeavored to assign to the Triestine Pathological and Anatomical
      Institute by strenghthening it with new laboratory methodologies. The
      establishment of a new "predominant and determining vision" in the international
      diagnostics of infectious disease was also emerging from the Haspurg city's
      hospital medicine. Indeed, it was here that in 1907, the brief scientific debate
      focussing on the cadaver of a coachman who had been infected by a glanders
      infected horse was apparently taking place only locally. Yet, it can now be seen
      as referring to what was happening on the international scale, in a setting that
      after a century of empiricism and morphologism, was characterized by the
      progressive penetration of laboratory medicine into clinical-anatomical medicine.

PMID- 16619982
TI  - Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic
      soft tissue: new entities and new variants of old entities recorded during the
      last 25 years. Part X: excerpta VIII.

PMID- 16619983
TI  - The Department of Surgery, University of Limpopo (Medunsa Canpus).

PMID- 16619984
TI  - Aggressive fibromatosis--impact of prognostic variables on management.
AB  - OBJECTIVE: To determine the impact of prognostic variables on local control in
      patients with aggressive fibromatosis treated with or without radiation.
      MATERIALS AND METHODS: Forty-two patients presenting to the combined sarcoma
      clinic at Johannesburg Hospital with aggressive fibromatosis from 1990 to 2003
      were analysed retrospectively. There were 14 males and 28 females. The lesions
      involved the head and neck in 6 cases (14%), the thorax in 6 (14%), the
      extremities in 19 (45%) and the abdomen in 11 (26%). Thirty-seven patients (88%)
      presented to the clinic for the first time, whereas 5 (12%) had recurrent disease
      at presentation. Fifteen patients (36%) underwent excision only, 15 (36%) had
      excision followed by postoperative radiation, 8 (19%) had biopsy only, and 4 (9%)
      had radiation only. The median dose of radiation was 60 Gy (range 9 - 70 Gy).
      RESULTS: One patient had local failure following excision and postoperative
      radiation therapy. The local control was 100% for surgery alone and 86% for
      surgery followed by postoperative radiation at > or = 24 months. On univariate
      analysis, age, sex, positive margins, primary or recurrent presentation, site of
      involvement and initial treatment did not affect local control significantly.
      Eight of 19 patients (42%) receiving radiation developed severe moist
      desquamation following treatment, and all these patients had doses of 60 Gy or
      more. CONCLUSION: Surgery with or without radiation therapy gave excellent local
      control. The addition of radiation therapy to surgery as well as other known
      prognostic parameters did not impact on local control. The morbidity of radiation
      treatment is considerable, as noted in this series, and adjuvant radiation
      therapy should therefore be considered only in situations where the risk of
      recurrence and the morbidity of re-excision are high.

PMID- 16619985
TI  - Impaired anastomotic healing after preoperative radiotherapy followed by anterior
      resection for treatment of rectal carcinoma.
AB  - BACKGROUND: Patients with rectal carcinoma undergoing total mesorectal excision
      (TME) have a lower recurrence rate with preoperative radiotherapy (RT). The aim
      of this study was to assess the side-effects in patients who had preoperative RT
      compared with those who did not receive it (because of palliative resections,
      advanced age or refusal). METHODS: From January 2001 to March 2003, 40 patients
      underwent resection and double-stapled anastomosis for rectal carcinoma. We
      compared 17 patients who received RT followed by resection and low rectal
      anastomosis, with 23 patients who did not have RT. RESULTS: After surgery 7/17 of
      the patients who had received RT developed anastomotic leaks. Anastomotic leakage
      was seen only once in the patients who did not have RT (41% v. 4%, p = 0.006). A
      protective stoma, which was performed in 11 patients in the RT group, did not
      prevent anastomotic leakage (4/11 leakage with stoma v. 3/6 leakage without
      stoma, p = 0.64). Median hospital stay was longer in the RT group (17.4 v. 13.7
      days, p = 0.017). There was no difference in the number of minor postoperative
      complications between the two groups (24% v. 22%). CONCLUSION: Compared with
      surgery alone, preoperative short-term RT increased the number of anastomotic
      leaks and hospital stay, whether or not a protective stoma was performed.

PMID- 16619986
TI  - Video-assisted thoracoscopic pericardial window for penetrating cardiac trauma.
AB  - OBJECTIVE: To report our experience with thoracoscopic pericardial window (TPW)
      for occult penetrating cardiac injury. PATIENTS AND METHODS: During the study
      period (1 January - 31 December 2000), a small group of haemodynamically stable
      patients with anterior left-sided praecordial wounds were selected for TPW. All
      patients underwent general anaesthesia with double-lumen intubation and collapse
      of the left lung. A rigid laparoscope was inserted through a 2 cm incision in the
      5th intercostal space in the anterior axillary line. Another 3 cm incision was
      made in the fourth intercostal space over the cardiac silhouette. Conventional
      instruments were used to grasp and open the pericardium. Any myocardial injury
      identified was an indication to proceed to sternotomy. In the absence of a
      myocardial injury and bleeding, the procedure was terminated and considered
      therapeutic. RESULTS: Seventy-one patients with suspected penetrating cardiac
      injuries were seen. TPW was successfully completed in 13 patients. All were men,
      with a mean age of 29.8 (range 19 - 38) years. Ten and 3 patients sustained stab
      and gunshot wounds, respectively. The mean revised trauma score was 7.84.
      Ultrasound was performed in 12 patients; the results were equivocal for 2
      patients, and positive for an effusion in 4 patients. Haemopericardium was found
      in 3 patients, 2 of whom proceeded to sternotomy. No cardiac injury was found in
      1, a left ventricular contusion was identified in the second, and the third
      patient had no further procedure after good video-thoracoscopic visualisation of
      the anterior myocardium revealed no injury. In another patient, pericardial
      bruising was evident without any haemopericardium. The mean operative time was
      13.4 (range 10 - 15) minutes, with a mean hospital stay of 5.4 (range 3 - 8)
      days. There were no complications. The use of a double-lumen endotracheal tube
      increased the cost of TPW by 23% when compared with subxiphoid pericardial window
      (SPW). CONCLUSION: TPW is a feasible, although in our setting not cost-effective,
      diagnostic option for occult penetrating cardiac injuries.

PMID- 16619987
TI  - Coagulation for the clinician.

PMID- 16619988
TI  - Caeco-vesical fistula--an unusual sequel of colonic tuberculosis.

PMID- 16619989
TI  - Going for the gold! Public health priorities.

PMID- 16619990
TI  - Individual rights, collective good and the duty of care.

PMID- 16619991
TI  - Mandatory immunization of health care providers: the time has come.

PMID- 16619992
TI  - Uptake and behavioural and attitudinal determinants of immunization in an
      expanded routine infant hepatitis B vaccination program in British Columbia.
AB  - INTRODUCTION: British Columbia (BC) implemented a universal infant hepatitis B
      (HB) immunization program in 2001. The study objective was to evaluate HB
      immunization coverage among the first six-month cohort of eligible infants in the
      province outside of the Vancouver-Richmond health region and to assess
      parent/guardian behavioural and attitudinal determinants of HB immunization.
      METHODS: A cross-sectional survey of HB immunization was conducted using a random
      sample of eligible infants born between 1 January-30 June 2001. HB immunization
      coverage data were obtained from the provincial Public Health Information System,
      and through a telephone survey of 487 of eligible infants' parents/guardians that
      was conducted between October 2002-January 2003. At this time, parents/guardians
      were also asked about behaviours and attitudes towards immunization, based on the
      Immunization Health Belief Model Scale. RESULTS: HB immunization coverage with at
      least one dose of HB vaccine was 89% and uptake of 3 doses of HB vaccine was 78%.
      HB immunization was significantly associated (p<0.001) with a recommendation for
      HB immunization from a health care professional. The main reason for non-HB
      immunization was parental concern about side effects. DISCUSSION: Seventy-eight
      percent of infants completed the 3-dose HB vaccination schedule. Parental
      behaviour regarding HB immunization of their children was strongly influenced by
      a supportive recommendation from either a nurse or doctor.

PMID- 16619993
TI  - Assessing road rage victimization and perpetration in the Ontario adult
      population: the impact of illicit drug use and psychiatric distress.
AB  - BACKGROUND: To investigate the association among illicit drug use, psychiatric
      distress and road rage victimization and offending. Particular attention is given
      to the most serious forms of road rage behaviour. METHODS: The data are based on
      the 2002 CAMH Monitor and include a sample of 2,421 Ontario adults aged 18 and
      older. Logistic regression analyses were conducted with illicit drug use and
      psychiatric distress (GHQ) and demographic factors as independent variables.
      RESULTS: Past-year road rage victimization was reported by 42% of the sample and
      31% reported any type of road rage offending. Approximately 5% were classified as
      respondents with serious road rage involvement. The logistic regression analyses
      revealed significant relationships between illicit drug use and road rage
      outcomes. Cannabis use was significantly associated with general road rage
      victimization and offending, while stimulant use substantially increased the
      likelihood of victimization and membership in the serious road rage
      classification. Psychiatric distress significantly increased the odds of both
      road rage victimization and serious road rage involvement. CONCLUSION: These data
      reveal different indicators of road rage offending, victimization and serious
      involvement. Further work is needed to clarify the mechanisms associated with the
      relationship among stimulant use, psychiatric distress and serious road rage
      involvement.

PMID- 16619994
TI  - Farm injuries and fatalities in British Columbia, 1990-2000.
AB  - BACKGROUND: Farming is considered to be one of the most dangerous occupations in
      Canada and internationally, as it often involves work in a high-risk environment
      due to exposure to such hazards as machinery, large animals and noxious
      chemicals. The objective of this study was to describe the incidence and nature
      of farm-related deaths and injuries on British Columbian farms from 1990-2000,
      with reference to Canadian averages. METHODS: British Columbian farm fatalities
      and farm injury hospitalizations data from Canadian Agricultural Injury
      Surveillance Program for 1990-2000 were analyzed in conjunction with the 1996 and
      2001 Canada Census of Agriculture. The incidence and nature of farm injuries were
      quantified and described for age, gender, cause of injury, primary diagnosis and
      agent of injury. RESULTS: There were 82 fatal injuries from 1990-2000 and 1,407
      hospitalizations from 1991/92 to 1999/2000. No significant overall incidence
      trends were found during the study period. The rate of machinery-related injuries
      requiring hospitalization is lower in BC than in Canada as a whole. The net
      effect of higher than expected hospitalization rates in younger BC adults (age 20
      49) and lower than expected hospitalization rates in older BC adults (age 70+)
      was a much slower increase in hospitalization rates as farmers get older.
      CONCLUSION: The current data suggest that higher than expected non-machinery
      related injuries result in higher hospitalization rates of young adult BC
      farmers. The potential impact of farm fatalities and injury in youth on loss of
      productivity and quality of life years emphasizes the need for education and
      prevention.

PMID- 16619995
TI  - Population health effects of air quality changes due to forest fires in British
      Columbia in 2003: estimates from physician-visit billing data.
AB  - BACKGROUND: Major forest fires near populated areas during 2003 exacted a huge
      economic toll on communities in British Columbia. We designed a study to examine
      associations between PM2.5 and PM10 levels and physician visits in two affected
      communities. METHODS: Measurements of 24-hour averages of particulate matter
      (PM10 and PM2.5) obtained from the monitoring network of the BC Ministry of
      Water, Land and Air Protection were used to define weeks where forest fires
      resulted in increases in ambient PM. Weekly rates of physician visits for
      respiratory (ICD-9 codes 460-519), cardiovascular (390-459) and mental illnesses
      (290-319) obtained through the Medical Services Plan of BC, were compared for
      2003 and aggregates of the 10 previous years. RESULTS: Both the Kelowna and
      Kamloops regions experienced five weeks of elevated 24-hour average PM levels,
      although maximum levels in Kelowna were greater. In the Kelowna region, increases
      in physician visits for respiratory diseases of between 46 and 78% above 10-year
      mean rates were observed for three weeks during the forest fire period. Similar
      effects were not observed in Kamloops. Effects on visits for cardiovascular
      diseases or mental disorders were not seen in either community. INTERPRETATION:
      Forest fire smoke was associated with an excess of respiratory complaints in
      Kelowna area residents. The lack of a similar effect in Kamloops is likely due to
      the population being exposed to lower levels of PM. The absence of apparent
      cardiovascular health effects may be due to selective effects of forest fire
      smoke on respiratory tract disease.

PMID- 16619996
TI  - [Prevalence and concurrent forms of violence against children in the Quebec
      population].
AB  - OBJECTIVE: To date, the phenomenon of concurrent forms of violence against
      children has received little consideration from research. This study sought to
      determine the prevalence and cooccurrence of various forms of violence (physical,
      sexual and psychological). METHOD: A telephone survey was conducted with a
      representative sample of 822 Quebec adults. RESULTS: More than one in three
      adults (36%) reported having experienced one form of violence in childhood. Ten
      percent (10%) of the adults experienced two forms of violence while 3% of the
      respondents reported having experienced all three forms of violence in childhood.
      Physical violence (22%) was the form most frequently reported, followed by
      psychological violence (16%) and sexual violence (14%). The different prevalence
      rates did not vary as a function of age. However, women were more likely to
      report having been sexually victimized (rape and fondling) and less likely to
      report having experienced physical violence. DISCUSSION: These results, including
      both the global rates and those particular to each gender, are comparable to
      findings in similar North American studies. The co-occurrence noted is salient
      enough to necessitate particular attention to diverse clinical clientele and to
      be considered in future research exploring the risk factors of violence and its
      subsequent sequelae.

PMID- 16619997
TI  - Prognostic relevance of census-derived individual respondent incomes versus
      household incomes.
AB  - BACKGROUND: Census-based measures of income derived from median income of a
      geographic area are often used in health research. Many national census surveys
      gather information on both the respondent's individual income and the income for
      the entire household, giving researchers a choice of census income measures. We
      compared the extent to which individual respondent income and household income
      (both obtained from census data) are associated with outcomes in a cohort of
      patients with cardiac disease. METHODS: We used data from the Alberta Provincial
      Project for Outcome Assessment in Coronary Heart Disease (APPROACH), where postal
      codes were linked to the Postal Code Conversion File (PCCF) to determine each
      patient's census Dissemination Areas (DA). DA-derived median household income and
      median individual income were obtained from the 2001 Canadian Census and survival
      outcomes were then directly determined for income groupings defined by quintile.
      Two-year survival adjusted for age and sex was described with a proportional
      hazards analysis. RESULTS: There were 9,397 patients undergoing cardiac
      catheterization between January 1, 2001 and March 31, 2002, with complete DA
      level median income measures. Household income quintiles yielded a wider spread
      of survival across quintiles (range of 2-year estimated survival, 91.8% to 95.9%
      for household income versus 92.8% to 95.6% for respondent income), as well as a
      more progressive decline in survival as income decreased. This progressive
      decline was not seen for the respondent income measure. CONCLUSIONS: The greater
      spread and progressive decline of survival for household income relative to
      respondent income leads us to conclude that household income is the better socio
      economic determinant of health in our data and for the outcome measure we
      studied.

PMID- 16619998
TI  - Mapping stairwell accessibility in Vancouver's downtown core.
AB  - BACKGROUND: The increase in obesity is due in part to changes in the environment
      that affect behaviours such as physical activity. Stairwells in buildings present
      an opportunity to increase physical activity in the workplace. We characterized
      the stairwell accessibility in business buildings in the downtown core of
      Vancouver. METHODS: Characteristics of the stairwells in business buildings with
      two or more floors were obtained. Stairwells were characterized based on their
      visibility from the main entrance, signage, presence of physical door, and
      interior lighting and space. Building completion year was obtained from the
      Vancouver City Hall. RESULTS: A total of 138 buildings in the pre-designated area
      were eligible for characterization. Due to security concerns, only 123 were
      assessed. Of those assessed, 54% had stairwells visible from the main entrance,
      33% had locked doors and only 18% had signs on the stairwell doors. Of the 83
      stairwells that were accessible, 54% and 36% were considered brightly lit and
      spacious enough for two people, respectively. Only 11% of the buildings studied
      had accessible stairwells that met all of our accessibility criteria. More
      recently built buildings tended to have a higher proportion of locked stairwell
      doors; otherwise, building completion year was not associated with any of the
      accessibility criteria. INTERPRETATION: Based on their environmental
      characteristics, very few buildings were set up in a way that encouraged stair
      use. For the work environment to be conducive to increased physical activity,
      building policy will need to consider the implications of design on activity
      patterns.

PMID- 16619999
TI  - Prevalence and factors related to Canadian workplace health programs.
AB  - BACKGROUND: This study documented the prevalence and factors related to workplace
      health programs in Canada, including Employee Assistance Programs (EAPs), drug
      testing programs, and Health Promotion Programs (HPPs). METHODS: A representative
      sample of 565 Human Resources Managers at worksites with 100 or more employees
      across Canada completed a questionnaire on the worksite characteristics and the
      types of programs at their workplace (response rate = 79.8%). RESULTS: EAPs were
      established in 67.8% of sampled worksites (95% CI: 63.9%-71.7%). The proportion
      of worksites with EAPs varied significantly across work sectors (p<0.001) but not
      across regions of Canada. Worksites with EAPs had significantly (p<0.001) fewer
      visible minorities and had more unionized employees (p<0.001) than worksites
      without EAPs. For drug-testing programs, about 10.3% of Canadian worksites have
      them (95% CI: 7.8%-12.8%). Significant differences were noted across regions
      (p<0.001) with Alberta most likely to have such programs (25.4%) and Ontario
      least likely (4.6%). Also, safety-sensitive worksites and those with United
      States ownership were significantly (p<0.05) more likely to have drug testing.
      The most common type of HPP was fitness programs (29.4%) and the least common was
      day/elder care programs (5.5%). Fitness programs were most common in the Eastern
      provinces and least common in Quebec. CONCLUSIONS: Overall, Canadian worksites
      favour a health promotion and treatment approach over a deterrence approach for
      addressing health and substance use issues in the workplace. Workplace health
      programs were related to several factors that have created an uneven system of
      health promotion, treatment and deterrence in Canadian worksites.

PMID- 16620000
TI  - Impact of antibiotic administrative restrictions on trends in antibiotic
      resistance.
AB  - CONTEXT: In March 2001, in response to concerns about increasing resistance to
      fluoroquinolone (FQ) antibiotics, the Ontario Drug Benefit (ODB) program limited
      reimbursement of FQs to ODB beneficiaries defined as high risk or in whom other
      therapies are not tolerated. OBJECTIVE: To analyze the impact of the limited use
      (LU) policy changes on antibiotic resistance rates in Ontario, focussing on
      community-acquired pathogens. DESIGN: Ontario data submitted to the Canadian
      Bacterial Surveillance Network (CBSN) between January 1, 1998 and June 30, 2002
      were analyzed for rates of resistance in various pathogen-antibiotic
      combinations. The effect of the LU policy on the level and rate of change of
      antibiotic resistance was estimated using time series models. RESULTS: Resistance
      rates for S. pneumoniae were 10-12% for penicillin, erythromycin and trimethoprim
      sulfamethoxazole (TMP/SMX) and less than 3% for amoxicillin and all three FQs
      tested. There was a statistically significant increasing trend in resistance
      rates of S. pneumoniae to amoxicillin and levofloxacin throughout the study
      period. Antibiotic resistance of S. pneumoniae to ciprofloxacin indicated a
      statistically significant decreasing trend over the study period with a
      statistically significant increase in the level of antibiotic resistance at the
      time of the LU policy implementation. No other indication of any statistically
      significant decrease in resistance rates associated with the LU policy was found.
      CONCLUSIONS: Although no direct cause and effect can be proven with these
      observational data, there is no evidence that the limited use policy to restrict
      fluoroquinolones decreased antibiotic resistance in any of the pathogen
      antibiotic combinations tested.

PMID- 16620001
TI  - Improvements in the status of folate and cobalamin in pregnant Newfoundland women
      are consistent with observed reductions in the incidence of neural tube defects.
AB  - BACKGROUND: Historically, the province of Newfoundland and Labrador had one of
      the highest rates of neural tube defects (NTDs) in North America (1976-1991:
      3.2/1000 births), which could be partially explained by the sub-optimal status of
      folate and cobalamin in this population. In order to gain evidence of the impact
      of folate fortification programs, as well as prenatal education programs, a cross
      sectional study was conducted to obtain data on the folate and cobalamin status
      of pregnant Newfoundland women in the post-folate fortification era.
      Additionally, the rates of NTDs were determined. METHODS: Blood samples were
      collected during the first prenatal clinic (at approximately 16 weeks gestation)
      from 365 pregnant women in Newfoundland in 2002. Samples were analyzed for serum
      folate, cobalamin and homocysteine. In addition, rates of neural tube defects
      were calculated from data collected from the Provincial Medical Genetics Program,
      Newfoundland. Data were compared to historical data from a similar population of
      pregnant women in Newfoundland. RESULTS: The status of both folate and cobalamin
      has significantly improved (p<0.0001) in the post-fortification era, concurrent
      with a significant reduction in the number of neural tube defects (NTDs), from
      4.67 (years 1992-1996) to 1.01 (years 1998-2002) per 1000 total births.
      INTERPRETATION: These data provide evidence that both folate and cobalamin status
      of pregnant Newfoundland women have improved since 1997. The data for cobalamin
      provide evidence that strategies in addition to folate fortification programs are
      contributing to the improvements of poor water-soluble vitamin status in this
      population, thus providing a partial explanation for the dramatic reductions in
      NTD rates observed since 1995.

PMID- 16620002
TI  - Influenza vaccination: a call for a multiple intervention approach.
AB  - Influenza seriously impacts the health and well-being of individuals and
      communities and has significant implications for the health care system. Despite
      known benefits of influenza vaccination, inoculation rates among health care
      providers remain low. Close proximity to patients, the potential to act as an
      infection vector and their role in patient education has focussed attention on
      how health care professionals make personal vaccination decisions. This
      commentary explores the inherent complexity of vaccination decision-making and
      offers suggestions for a multiple intervention approach to address health care
      providers' vaccination uptake needs. Directions for future research are also
      discussed.

PMID- 16620003
TI  - Addressing the emergence of pediatric vaccination concerns: recommendations from
      a Canadian policy analysis.
AB  - Ever since the advent of pediatric vaccination, individuals have expressed
      concerns about both its risks and benefits. These concerns have once again
      resurfaced among some segments of the population and could potentially undermine
      national vaccination programs. The views of the public, however, must be
      considered and respected in the formulation of vaccination policy. We have
      conducted an analysis of the pediatric vaccination "debate" in the Canadian
      context. We believe that there is common ground between those who support
      pediatric vaccination and those who are concerned about these programs. Based on
      our findings, we believe that the goal of public health authorities should be to
      maintain trust in vaccines by continuing to meet certain reciprocal
      responsibilities. To do so, we recommend the following: 1) increased investment
      in adverse event reporting systems; 2) request for proposals for consideration of
      a no-fault compensation program; 3) developing pre-emptive strategies to deal
      with potential vaccine risks; 4) further examination of mechanisms to improve
      communication between physicians and parents concerned about vaccination. All of
      these approaches would require additional investment in pediatric vaccination.
      However, such an investment is easy to justify given the benefits offered by
      pediatric vaccination and the ramifications of failing to maintain confidence in
      vaccination programs or missing a vaccine-related adverse event.

PMID- 16620004
TI  - Global Health Watch Canada? Mobilizing the Canadian public health community
      around a global health advocacy agenda.
AB  - Growing poverty, collapsing health care systems, the AIDS pandemic and the
      widening of health and health care inequities within and between countries all
      point to the limited success of global public health interventions over the past
      few decades. Notwithstanding the efforts of multilateral agencies such as the
      World Health Organization and the many existing contributions from the Canadian
      community of health professionals, this commentary argues and appeals for further
      action particularly in relation to the social and political impediments to better
      health and justice. Specifically, it calls for the development of a robust
      instrument to assess the impact of Canada as a whole on the state of global
      health, and to monitor the performance of key Canadian institutions. It is
      suggested that such an instrument would result in a process that enhances global
      citizenship and public accountability, and buttresses the efforts of civil
      society to forge trans-national links in pursuit of a fairer and healthier world.
      Public health professionals, by virtue of their social standing as well as the
      nature and tools of their discipline, should be at the forefront of such civic
      efforts.

PMID- 16620005
TI  - How can PhD research contribute to the global health research agenda?
AB  - We propose that PhD and post-doctoral researchers are a strong, untapped resource
      with the potential to make a real contribution to global health research (GHR).
      However, we raise some ethical, institutional and funding issues which either
      discourage new researchers from entering the field or diminish their capacity to
      contribute. We offer a number of recommendations to Canadian academic and non
      academic institutions and funders, and aim to generate discussion among them
      about how to overcome these constraints. We need changes in the way graduate
      research is organized and funded, to create opportunities to work collaboratively
      within established low- and middle-income country (LMIC)/Canadian research
      partnerships. We urge changes in the way institutions fund, recognize, value and
      support GHR, so established researchers are encouraged to develop long-term LMIC
      relationships and mentor new Canadian/LMIC researchers. We ask funders to
      reconsider additional GHR activities for support, including strategic training
      initiatives and dissemination of research results. We also encourage the
      development of alternative institutions that can provide training and mentoring
      opportunities. GHR per se faces many challenges. If we address those that reduce
      our potential to contribute, we can become real partners in GHR, working towards
      equitable global health and solutions to priority health issues.

PMID- 16620006
TI  - A model of mechanisms underlying the influence of media on health behaviour
      norms.
AB  - Media-based interventions are common in health promotion, yet their conceptual
      underpinnings tend to be based on a simple linear model of direct influence on
      individuals' health behaviour. Recent studies have suggested that the processes
      through which media influence health behaviours are actually far more complex.
      This paper presents a conceptual model of how the medias influence the emergence
      and maintenance of the social norms that can contribute to shaping health
      behaviours. Through positive (amplifying) and negative (dampening) loops, a total
      of six potential influence pathways are proposed, and the role of opinion leaders
      and specialists is specified. Future directions for empirical tests of the model
      are identified.

PMID- 16620007
TI  - Fitting audiology within the population health perspective.
AB  - The population health perspective has become increasingly apparent in the
      medical, public health, and policy literature. This article emphasizes the value
      of applying the population health perspective and associated frameworks to the
      rehabilitative sciences and particularly to the field of audiology. Key
      components of the population health perspective--including the determinants of
      health, the importance of evidence-based practice, and the value of
      transdisciplinarity--are used to illustrate the relevance of population health to
      the field of audiology. Using these key concepts from a population health
      framework and examples from audiology, the adoption of a population health
      perspective is proposed.

PMID- 16620008
TI  - Structure and function of the gut mucosal immune system.

PMID- 16620009
TI  - Functional aspects of the mucosal immune system.

PMID- 16620010
TI  - Recent progress in inflammatory bowel disease genetics.

PMID- 16620011
TI  - Microbial and dietary factors in the pathogenesis of chronic, immune-mediated
      intestinal inflammation.

PMID- 16620012
TI  - Experimental models of mucosal inflammation.

PMID- 16620013
TI  - Overview of role of the immune system in the pathogenesis of inflammatory bowel
      disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are caused by the over-activity
      of the immune system. Current and novel therapies are designed to dampen these
      over-active responses. Analysis of the types of immune responses ongoing in
      diseased mucosa of inflammatory bowel disease patients has revealed that CD and
      UC are fundamentally different diseases. The former has the molecular imprints of
      a Th1 dominant cell-mediated hypersensitivity response whereas the latter appears
      to involve antibody-mediated hypersensitivity.

PMID- 16620014
TI  - The role of the epithelial barrier in inflammatory bowel disease.

PMID- 16620016
TI  - Alterations of T lymphocytes in inflammatory bowel diseases.

PMID- 16620015
TI  - Involvement of dendritic cells in the pathogenesis of inflammatory bowel disease.
AB  - In conclusion, during inflammation, DCs are likely activated by inflammatory
      signals and induced to migrate to T cell zones of organized lymphoid tissues
      where the cells induce T cell responses. In addition to their established role in
      T cell priming and the induction of tolerance, DCs may act to enhance (or
      possibly suppress) T cell responses at sites of mucosal inflammation. Determining
      the importance of DCs in this regard, as well as establishing a potential role
      for DCs in continuous activation of naive or central memory cells in lymph nodes
      draining inflammatory sites, will elucidate the role of DCs as a potential
      therapeutic target for chronic inflammatory diseases, like IBD. Resident
      intestinal macrophages are noninflammatory and do not efficiently present
      antigens to intestinal T cells, yet are avidly phagocytic and able to kill
      internalized organisms. During intestinal inflammation, monocytes are recruited
      from the blood, become inflammatory macrophages in the inflamed tissue, and are
      major contributors to tissue destruction and perpetuation of inflammation via
      their production of chemokines and pro-inflammatory cytokines. Macrophages may
      also contribute directly to DC activation and maturation, which would drive DCs
      to present antigens from the bacterial flora to T cells locally within tissue or
      to more efficiently traffic to T cell zones of lymphoid tissue. Thus, DCs and
      macrophages have evolved functional niches that promote cooperation in the
      prevention of untoward intestinal inflammation in the steady state and in the
      eradication of invasive microorganisms during infection. The balance between
      suppressing inflammation and promoting host defense is altered in humans with IBD
      allowing a persistent inflammatory response to commensal bacteria. Based on
      studies from animal models, the pathogenesis of IBD likely involves either the
      lack of appropriate regulation from T cells, or an over-production of effector T
      cells. The end result of these potential mechanisms is the abnormal induction
      and/or survival of effector T cells and the production of factors such as
      cytokines by inflammatory macrophages and neutrophils that result in tissue
      destruction. The destructive process likely involves normally tolerizing DCs,
      which in the microenvironment of the inflamed mucosa activate T cell responses to
      normal flora in both draining lymphoid tissues and at sites of inflammation, with
      macrophages and neutrophils contributing the bulk of inflammatory and destructive
      cytokines.

PMID- 16620017
TI  - The B-cell system in inflammatory bowel disease.
AB  - Secretory immunity is the best-defined part ot the mucosal immune system. This
      adaptive humoral defense mechanism depends on a fine-tuned cooperation between
      secretory epithelia and local plasma cells. Such mucosal immunocytes produce
      preferentially dimers and larger polymers of immunoglobulin A (collectively
      called pIgA), which contain J chain and therefore can bind to the epithelial
      secretory component (SC). This transmembrane glycoprotein functions as pIg
      receptor (pIgR) that also translocates pentameric IgM to the epithelial surface.
      B cells with a high level of J-chain expression and pIg-pIgR interactions at
      mucosal effector sites are thus necessary for the generation of secretory
      antibodies (SIgA and SIgM). Secretory antibodies perform immune exclusion in a
      first-line defense, thereby counteracting microbial colonization and mucosal
      penetration of soluble antigens. However, local production of pIgA is
      significantly down-regulated in inflammatory bowel disease (IBD), as revealed by
      strikingly decreased J-chain expression. Although the total increase of the
      immunocyte population in IBD lesions probably compensates for the relatively
      reduced pIgA production, decreased pIgR/SC expression in regenerating and
      dysplastic epithelium signifies that the SIgA system is topically deficient.
      There is, moreover, a significant shift from IgA2 to IgA1 production, the latter
      subclass being less resistant to proteolytic degradation. These changes--together
      with activation of mucosal macrophages and a dramatic increase of IgG-producing
      cells--may reflect local establishment of a second defense line which, however,
      is unsuccessful in its attempt to eliminate antigens derived from the indigenous
      microbial flora. Such a 'frustrated' local humoral immune system results in
      altered immunological homeostasis and jeopardized mucosal integrity. Complement
      activation observed in relation to epithelium-bound IgG1 in ulcerative colitis
      indicates, moreover, that the surface epithelium is subjected to immunological
      attack by an autoimmune reaction. These luminal deposits regularly contain
      terminal cytotoxic complement, and often also C3b as a sign of persistent
      activation. Comparison of identical twins, discordant with regard to ulcerative
      colitis, suggests that the markedly skewed local IgG1 response seen in this IBD
      entity may be genetically determined. The initial event(s) eliciting B-cell
      driven immunopathology in IBD remains unknown. Abrogation of oral tolerance to
      certain antigens from commensal bacteria has been suggested as a putative early
      mechanism, and lymphoid neogenesis and hyperplasia in the lesions most likely
      signify massive microbial overstimulation of the local B-cell system. Such
      ectopic lymphoid microcompartments may contribute substantially to the
      proinflammatory systemic-type of B-cell responses occurring in established IBD
      lesions.

PMID- 16620018
TI  - Alterations of mesenchymal and endothelial cells in inflammatory bowel diseases.
AB  - The pathogenesis of complex chronic diseases like inflammatory bowel disease
      (IBD) can no longer be viewed as a one-way street in which classical immune cells
      have exclusive control over the initiation, duration and outcome of the disease.
      There is enough experimental evidence to demonstrate that nonimmune cells, among
      which are mucosal mesenchymal and endothelial cells, also play a decisive role by
      interacting with immune cells and establishing a two-way reciprocal exchange of
      signals and responses that dictate the ultimate outcome of inflammation. Smooth
      muscle cells and fibroblasts/myofibroblasts display a variety of immune functions
      and modulate the activity and survival of T-cells. Mucosal microvascular cells,
      through the expression of adhesion molecules and secretion of chemokines,
      regulate the quantity and quality of leukocytes transmigrating into the
      interstitial space. A number of receptor-ligand pairs are expressed by immune and
      nonimmune cells that control their functional interplay, but the CD40/CD40 ligand
      system may be the most effective because CD40 is expressed by activated muscle
      and endothelial cells, while the CD40 ligand is expressed by activated T-cells
      and platelets. The activation of this system in IBD can lead to the establishment
      of a continuous cycle of nonimmune cell-dependent, antigen-independent
      interactions that perpetuates gut inflammation.

PMID- 16620019
TI  - Role of mast cells and eosinophils in neuroimmune interactions regulating mucosal
      inflammation in inflammatory bowel disease.

PMID- 16620020
TI  - Multiparameter analysis of immunogenetic mechanisms in clinical diagnosis and
      management of inflammatory bowel disease.
AB  - The integrity of the intestinal mucosa depends on a functional coordination of
      the epithelium, lumenal microorganisms, and the local immune system. The
      mammalian immune system is superbly organized for innate and adaptive recognition
      of microbial antigens, a defensive capacity that must be balanced against the
      tissue damage produced by immune activity to preserve normal intestinal function.
      Inflammatory bowel disease (IBD) is generally thought to reflect an impairment in
      this balance, due to a combination of host genetic traits that shift the balance
      of immune and epithelial function to commensal microbiota, and perhaps the
      composition or activity of certain microbial elements as well. There has been
      much progress defining the fundamental disorders of these host traits,
      immunologic processes, and microbial targets in inflammatory bowel disease. Other
      fields of clinical and geologic microbiology are teaching us about the dynamic
      interaction of commensal bacteria with their host environment. These lines of
      investigation have revealed not only important insights about inflammatory bowel
      disease (IBD) pathogenesis, but also defined technologies and tools useful for
      its diagnosis and clinical management. This review focuses on these advances at
      the translational interface. We will first consider the innate anti-microbial
      response, centering on the utility of NOD2 genotyping for predicting disease
      susceptibility, prognosis, and therapeutic response profile. We will then turn to
      the adaptive anti-microbial response, focusing on the application of antibodies
      to fungal and bacterial species and products for Crohn's disease (CD) diagnosis
      and prognosis, and immunogenetics of T cell immunosuppression management.
      Finally, we will describe autoimmune mechanisms in IBD, with particular attention
      to autoantibodies in IBD diagnosis and infliximab responsiveness. We will
      conclude with the concept of multiparameter analysis of patients, to refine
      patient characterization and stratification in diagnosis and clinical management.

PMID- 16620021
TI  - The role of probiotics and antibiotics in regulating mucosal inflammation.
AB  - Antibiotic and probiotic agents have increasingly moved in the focus of basic and
      clinical research as well as clinical trials for IBD therapy. Both approaches
      modulate the intestinal flora, the former through eradication or reduction, the
      latter through establishment or increase of luminal bacteria. Although clinical
      trials provide proof of principle that both approaches can be therapeutically
      successfull, we just start to understand the mechanims and may get a first
      feeling for the potential and limitations of these "microbial" therapies. As
      basic research sets out to dissect the field using extensive efforts and new
      technologies, a more detailed exploration of the genetic, immune and microbial
      factors that govern the life-long crosstalk between host and intestinal flora is
      already opening new insight into general aspects of human immunology, immune
      regulation, IBD pathogenesis and therapy.

PMID- 16620022
TI  - From immunogenic mechanisms to novel therapeutic approaches in inflammatory bowel
      disease.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are the two most common forms of
      chronic inflammatory bowel disease (IBD). The etiology of IBD is still unclear
      and should be considered as multi-factorial according to recent studies. Genetic
      factors seem to play a pathogenetic role as well as environmental, infectious and
      immulogical factors. Substantial progress, however, has been made in the
      understanding of the pathogenesis of IBD during the past years persuing the view,
      that IBD could result from disturbances of the intestinal barrier and a
      pathologic activation of the intestinal immune response towards luminal,
      bacterial antigens. This paradigm has led to the identification of key players of
      the intestinal immune system, which represent promising targets for novel
      therapeutic approaches. The objective of this chapter is to provide an overview
      over recent advances in the elucidation of the intestinal immune system in IBD
      and novel therapeutic approaches that have been derived from these results.
      Molecular biological techniques have revealed, that many of the established
      conventional antiinflammatory drugs such as salicylic acids, steroids or
      immunuosuppressants act at the same molecules that are the target for modern
      biologicals, i.e., the cytokine TNF or the transcription factor NFkappaB. This
      chapter, however, focusses on novel experimental approaches such as recombinant
      antiinflammatory cytokines, neutralizing antibodies or antisense
      oligonucleotides.

PMID- 16620023
TI  - Making myc.
AB  - Myc regulates to some degree every major process in the cell. Proliferation,
      growth, differentiation, apoptosis, and metabolism are all under myc control. In
      turn, these processes feed back to adjust the level of c-myc expression. Although
      Myc is regulated at every level from RNA synthesis to protein degradation, c-myc
      transcription is particularly responsive to multiple diverse physiological and
      pathological signals. These signals are delivered to the c-myc promoter by a wide
      variety of transcription factors and chromatin remodeling complexes. How these
      diverse and sometimes disparate signals are processed to manage the output of the
      c-myc promoter involves chromatin, recruitment of the transcription machinery,
      post-initiation transcriptional regulation, and mechanisms to provide dynamic
      feedback. Understanding these mechanisms promises to add new dimensions to models
      of transcriptional control and to reveal new strategies to manipulate Myc levels.

PMID- 16620024
TI  - Transcriptional activation by the Myc oncoprotein.
AB  - The Myc transcription factor functions as a downstream effector of most mitogenic
      signals. Myc is synthesized rapidly in response to extracellular mitogenic
      signals, and blocking Myc induction abolishes or at least severely attenuates any
      mitogenic response. Furthermore, ectopic Myc expression can often bypass the
      requirement for extracellular signals for entry into S phase. Thus, the Myc
      transcription factor is both necessary and in many ways sufficient to promote the
      growth of diverse cell types. Given this potent biological activity, it is not
      surprising that mutations in the myc gene are among the most frequent in human
      and animal cancers. Understanding the molecular basis of Myc function has been a
      central issue in the fields of cancer biology and signal transduction for 20
      years.

PMID- 16620025
TI  - Mechanisms of transcriptional repression by Myc.
AB  - Myc proteins are nuclear proteins that exert their biological functions at least
      in part through the transcriptional regulation of large sets of target genes.
      Recent microarray analyses show that several percent of all genes may be directly
      regulated by Myc. A large body of data shows that Myc proteins both positively
      and negatively affect transcription. The basic mechanism underlying Myc's
      activation of transcription is well understood, but the mechanisms through which
      Myc negatively regulates or represses transcription are far less understood. In
      this chapter, we will review our current knowledge about this less-well
      understood topic.

PMID- 16620026
TI  - The Mad side of the Max network: antagonizing the function of Myc and more.
AB  - A significant body of evidence has been accumulated that demonstrates decisive
      roles of members of the Myc/Max/Mad network in the control of various aspects of
      cell behavior, including proliferation, differentiation, and apoptosis. The
      components of this network serve as transcriptional regulators. Mad family
      members, including Mad1, Mxi1, Mad3, Mad4, Mnt, and Mga, function in part as
      antagonists of Myc oncoproteins. At the molecular level this antagonism is
      reflected by the different cofactor/chromatin remodeling complexes that are
      recruited by Myc and Mad family members. One important function of the latter is
      their ability to repress gene transcription. In this review we summarize the
      current view of how this repression is achieved and what the consequences of Mad
      action are for cell behavior. In addition, we point out some of the many aspects
      that have not been clarified and thus leave us with a rather incomplete picture
      of the functions, both molecular and at the cellular level, of Mad family
      members.

PMID- 16620028
TI  - Myc target transcriptomes.
AB  - The c-Myc oncogenic transcription factor plays a central role in many human
      cancers through the regulation of gene expression. Although the molecular
      mechanisms by which c-Myc and its obligate partner, Max, regulate gene expression
      are becoming better defined, genes or transcriptomes that c-Myc regulate are just
      emerging from a variety of different experimental approaches. Studies of
      individual c-Myc target genes and their functional implications are now
      complemented by large surveys of c-Myc target genes through the use of
      subtraction cloning, DNA microarray analysis, serial analysis of gene expression
      (SAGE), chromatin immunoprecipitation, and genome marking methods. To fully
      appreciate the differences between physiological c-Myc function in normal cells
      and deregulated c-Myc function in tumors, the challenge now is to determine how
      the authenticated transcriptomes effect the various phenotypes induced by c-Myc
      and to define how c-Myc transcriptomes are altered by the Mad family of proteins.

PMID- 16620027
TI  - Structural aspects of interactions within the Myc/Max/Mad network.
AB  - Recently determined structures of a number of Myc family proteins have provided
      significant insights into the molecular nature of complex assembly and DNA
      binding. These structures illuminate the details of specific interactions that
      govern the assembly of nucleoprotein complexes and, in doing so, raise more
      questions regarding Myc biology. In this review, we focus on the lessons provided
      by these structures toward understanding (1) interactions that govern
      transcriptional repression by Mad via the Sin3 pathway, (2) homodimerization of
      Max, (3) heterodimerization of Myc-Max and Mad-Max, and (4) DNA recognition by
      each of the Max-Max, Myc-Max, and Mad-Max dimers.

PMID- 16620029
TI  - c-Myc, genome instability, and tumorigenesis: the devil is in the details.
AB  - The c-myc oncogene acts as a pluripotent modulator of transcription during normal
      cell growth and proliferation. Deregulated c-myc activity in cancer can lead to
      excessive activation of its downstream pathways, and may also stimulate changes
      in gene expression and cellular signaling that are not observed under non
      pathological conditions. Under certain conditions, aberrant c-myc activity is
      associated with the appearance of DNA damage-associated markers and karyotypic
      abnormalities. In this chapter, we discuss mechanisms by which c-myc may be
      directly or indirectly associated with the induction of genomic instability. The
      degree to which c-myc-induced genomic instability influences the initiation or
      progression of cancer is likely to depend on other factors, which are discussed
      herein.

PMID- 16620030
TI  - Lessons learned from Myc/Max/Mad knockout mice.
AB  - The past two decades of gene targeting experiments have allowed us to make
      significant strides towards understanding how the Myc/Max/Mad network influences
      multiple aspects of cellular behavior during development. Here we summarize the
      findings obtained from the myc/max/mad knockout mice generated to date, namely
      those in which the N-myc, c-myc, L-myc, mad1, mxi1, mad3, mnt, or max genes have
      been targeted. A compilation of lessons we have learned from these myc/max/mad
      knockout mouse models, and suggestions as to where future efforts could be
      focused, are also presented.

PMID- 16620031
TI  - Myc/Max/Mad in invertebrates: the evolution of the Max network.
AB  - The Myc proto-oncogenes, their binding partner Max and their antagonists from the
      Mad family of transcriptional repressors have been extensively analysed in
      vertebrates. However, members of this network are found in all animals examined
      so far. Several recent studies have addressed the physiological function of these
      proteins in invertebrate model organisms, in particular Drosophila melanogaster.
      This review describes the structure of invertebrate Myc/Max/Mad genes and it
      discusses their regulation and physiological functions, with special emphasis on
      their essential role in the control of cellular growth and proliferation.

PMID- 16620032
TI  - The Mlx network: evidence for a parallel Max-like transcriptional network that
      regulates energy metabolism.
AB  - Recent experiments suggest the existence of a transcriptional network that
      functions in parallel to the canonical Myc/Max/Mad transcriptional network.
      Unlike the Myc/Max/Mad network, our understanding of this network is still in its
      infancy. At the center of this network is a Max-like protein called Mlx; hence we
      have called this network the Mlx network. Like Max, Mix interacts with
      transcriptional repressors and transcriptional activators, namely the Mad family
      and the Mondo family, respectively. Similar to Max-containing heterodimers, Mlx
      containing heterodimers recognize CACGTG E-box elements, suggesting that the
      transcriptional targets of these two networks may overlap. Supporting this
      hypothesis, we have observed genetic interactions between the Drosophila
      melanogaster orthologs of Myc and Mondo. In higher eukaryotes, two proteins,
      MondoA and MondoB/CHREBP/WBSCR14, constitute the Mondo family. At present little
      is known about the transcriptional targets of MondoA; however, pyruvate kinase is
      a putative target of MondoB/CHREBP/WBSCR14, suggesting a function for the Mondo
      family in glucose and/or lipid metabolism. Finally, unlike the predominant
      nuclear localization of Myc family proteins, both Mondo family members localize
      to the cytoplasm. Therefore, while the Myc and Mondo families may share some
      biological functions, it is likely each family is under distinct regulatory
      control.

PMID- 16620033
TI  - Oral health behaviour of children and adults in urban and rural areas of Burkina
      Faso, Africa.
AB  - OBJECTIVES: To assess the level of dental knowledge and attitudes among 12 year
      old children and 35-44 year-olds in Burkina Faso; to evaluate the pattern of oral
      health behaviour among these cohorts in relation to location, gender and social
      characteristics and; to evaluate the relative effect of social-behavioural risk
      factors on caries experience. DESIGN: Across sectional study including urban and
      rural subgroups of population. SAMPLE AND METHODS: Multistage cluster sampling of
      households in urban areas; in rural areas random samples of participants were
      based on the recent population census. The final study population covered two age
      groups: 12 years (n = 505) and 35-44 years (n = 493). RESULTS: For both children
      and adults, levels of oral health knowledge, attitudes and self-care were low;
      36% of 12-year-olds and 57% of 35-44-year-olds carried out toothcleaning on a
      daily basis. Pain and discomfort from teeth were common while dental visits were
      infrequent. Tooth cleaning was mostly performed by use of chewsticks. Use of
      toothpaste was rare, particularly fluoridated toothpaste was seldom; 9% of 12
      year-olds and 18% of 35-44-year-olds reported use of fluoride toothpaste.
      Significant differences were found in oral health knowledge, attitudes and
      practices according to location and gender. At age 12, important factors of high
      caries experience were location (urban), and consumption of soft drinks and fresh
      fruits. In 35-44-year-olds, gender (female), high education level, dental visit
      and occupation (government employee) were the significant factors of high dental
      caries experience whereas adults using traditional chewing sticks had lower DMFT.
      CONCLUSIONS: Health authorities should strengthen the implementation of oral
      disease prevention and health promotion programmes rather than traditional
      curative care. Community-oriented essential care and affordable fluoride
      toothpaste should be encouraged.

PMID- 16620034
TI  - Atraumatic Restorative Treatment (ART): the Tanzanian experience.
AB  - OBJECTIVES: Atraumatic Restorative Treatment (ART), which involves the use of
      hand instruments, is a relatively inexpensive, non-sophisticated, tooth
      conservative technique that offers the opportunity for restorative work in remote
      areas without electricity. The objectives of this survey were to evaluate the
      experience of dental practitioners with ART and the impact of the technique on
      oral health care in Tanzania, where ART was pioneered. METHODS: Dental officers
      (DOs), assistant dental officers (ADOs) and dental therapists (DTs) from
      different parts of the Tanzania mainland participated in a cross-sectional study
      that gathered information using a self-administered structured questionnaire.
      RESULTS: Only 41 (35%) of the 117 respondents were practising ART with only 6.5%
      of them doing so either "most of the time" or "always". Practising ART was
      significantly associated with the cadre of the dental practitioner, being higher
      among ADOs (50%) than DOs (37%) and DTs (20%), and with ART training, but was not
      related to either working experience or material availability. CONCLUSIONS: To
      date, ART has made little impact on oral health care delivery in Tanzania, where
      dental extractions still account for over 90% of all forms of dental treatment,
      and restorative work for less than 5%. Several problems in providing ART were
      noted, such as limited practical training and practice in ART, scarce resources,
      and lack of advocacy. RECOMMENDATIONS: An increased involvement and support for
      ART from the Ministry of Health and professional organisations, and public
      education of ART is called for.

PMID- 16620035
TI  - The proportion of pseudo-halitosis patients in a multidisciplinary breath
      malodour consultation.
AB  - AIM: To report the data from a multidisciplinary bad breath consultation in
      Germany. MATERIALS AND METHODS: In this cross sectional study, 407 patients
      attending a bad breath consultation were examined by a specially trained dentist,
      with an ENT-specialist, an internist, and a psychologist on call. RESULTS: All
      patients reported suffering from bad breath but only 72.1% showed detectable
      signs of breath malodour. Within this group, 92.7% revealed an oral cause, 7.3%
      revealed an extra-oral cause. Within the group without malodour, 76.3% had
      received prior diagnostics and treatments from other doctors, whereby 36% had
      received one or more gastroscopies and 14% had undergone an ENT operation. In
      only ten cases had an organoleptic evaluation of the putative malodour been
      performed. CONCLUSION: Our data reveal that breath malodour is mainly of oral
      origin and that patients with pseudo-halitosis are frequently not diagnosed
      correctly by doctors, resulting in a considerable amount of over-treatment.

PMID- 16620036
TI  - A proposal for a new classification of lesions of exposed tooth surfaces.
AB  - In the presence of improved methods of identification and treatment of lesions on
      the exposed surfaces of teeth, it should now be acknowledged that the GV Black
      "classification of carious cavities" is out of date. This paper describes a new
      system, proposed in 1997, discussed broadly throughout the profession, and
      eventually modified. The system has been adopted in several regions around the
      world as being a useful corollary to the current developing concept of minimal
      intervention dentistry. It is now desirable to adopt a new approach to the
      identification and recording of the lesions caused by both caries and non-carious
      tooth loss. A major advantage arising from its adoption would be that it would
      encourage the profession to minimise the amount of normal healthy tooth structure
      that is often sacrificed in pursuit of the cavity designs as suggested by Black.
      The authors are members of a Project Group of the FDI Science Committee, and this
      paper explains the concept and offers justification for the adoption of the
      system.

PMID- 16620037
TI  - The oral health status of street children in Adana, Turkey.
AB  - AIM: To determine the oral health status of street children and compare the
      results with a group of non-working children in Adana, Turkey. Street children
      are generally defined as any boy or girl for whom the street has become his or
      her habitual abode and/or source of livelihood; and who is inadequately
      protected, supervised, or directed by responsible adults. STUDY DESIGN:
      Demographic data including education, employment and social insurance of parents
      and number of siblings, was obtained. A formal interview with structured
      questions was used in order to determine the oral health behaviour of the
      children. Oral examinations were performed according to the criteria of the WHO
      oral examination form. RESULTS: The oral health behaviour of street children was
      significantly different from non-working children. While DMFT and dmft scores of
      the street youths were significantly lower than the control group, they had
      higher CPITN scores (p< or =0.001). CONCLUSION: Street children are commonly
      faced with oral health problems, especially periodontal problems. Therefore, the
      dental and periodontal needs of this particular population must be addressed.
      Oral health policies and preventive services including oral health promotion
      programmes which aim to give information about dental issues and to make positive
      changes in behavioural and environmental factors should be developed. The
      priority should be to control the factors which result in the occurrence of new
      dental problems.

PMID- 16620038
TI  - Khat chewing amongst UK resident male Yemeni adults: an exploratory study.
AB  - AIM: This cross sectional study recruited adult male Yemeni residents in
      Sheffield and Birmingham, UK, to assess their use of khat. METHODS: Structured
      interviews were conducted in both areas during weekly khat chewing sessions. The
      data collected included socio-demographic characteristics, khat use, dependency
      on khat, psychological functioning of chewers (GHQ-12) and nicotine dependency.
      Patterns of khat use, dependency and psychological functioning were correlated
      with age and self-reported oral problems. RESULTS: 75 khat chewing volunteers
      (mean age 40.75 years) were interviewed. Average age of starting khat chewing was
      17 years. The weekly amount chewed ranged from 0.25-3.0 khat bundles. Older
      respondents were more likely to be frequent chewers (p<0.025). 39% were assessed
      as dependent on khat, which correlated with frequency of use (p<0.041) and being
      in debt (p<0.046). Khat chewing correlated with nicotine dependence (p< 0.014).
      Self-reported oral problems correlated with both nicotine (p<0.04) and khat
      dependence (p<0.001). 93% reported that khat chewing promoted excessive smoking
      and 12% that this practice had initiated their tobacco use. CONCLUSIONS: Khat
      chewing creates dependency and correlates with tobacco smoking and nicotine
      dependence. Further research should investigate the correlations between khat and
      nicotine dependence. Development of a specific measure of khat dependence is
      recommended.

PMID- 16620039
TI  - Monitoring of vital signs during dental care.
AB  - Advances in medicine have greatly increased the survival of patients with severe
      health problems and have significantly prolonged life in elderly individuals with
      systemic disorders. Concomitant advances in dentistry and evolving societal
      expectations regarding dental health and function have likewise ensured that
      these patients are increasingly retaining their teeth and/or seeking dental care.
      The administration of local anaesthetics and the performance of extensive dental
      procedures may cause stress and systemic disturbances in such patients. In order
      to avoid potentially serious reactions, dentists are obligated to monitor
      continuously their medically challenged patients. Monitoring provides three
      important benefits. First, it helps the dentist detect acute medical emergencies
      that may require an immediate response. Second, monitoring may reveal gradual
      deleterious trends that can often be easily reversed before a true emergency
      occurs. Third, monitoring can assist the dentist in evaluating the efficacy of
      any emergency treatments or preventive measures that are rendered. The purposes
      of this article are to: briefly review monitoring techniques and devices, discuss
      their suitability for use in the dental office, and provide some tips for their
      application during dental care. In overall decreasing order of routine
      importance, monitoring resources include the following: responsible personnel,
      non-invasive blood pressure monitor, pulse oximeter, ECG, and the pretracheal
      stethoscope or capnograph.

PMID- 16620040
TI  - The responsibilities and rights of dental professionals 1. Introduction.
AB  - Dentists have well-defined legal, professional and ethical duties to their
      patients, the public and the profession. However, regular evaluations are
      necessary because their role and responsibilities are continually changing under
      the influence of a variety of internal and external forces and they further
      broaden as the profession evolves. Although a significant emphasis is placed on
      their responsibilities, professional rights of dentists also deserve particular
      interest because they are intimately related with these responsibilities.
      Furthermore, these rights enable dentists to serve and protect their patients and
      the community, provide quality care and comply with their broad responsibilities.
      In the first part of this series of three articles the responsibilities of
      dentists are analysed, while the second part focuses on the dentists'
      professional rights.

PMID- 16620041
TI  - Bridging the gap: the impact of patient choice on wound care.

PMID- 16620042
TI  - The role of surgery in the management of venous leg ulcers.

PMID- 16620043
TI  - A study comparing two objective methods of quantifying the production of wound
      exudate.
AB  - OBJECTIVE: The objective assessment of chronic wound therapies for exudate
      management (WRAP study) tested a variety of methods that could be used to improve
      understanding of dressing performance in the presence of wound exudate, including
      measurement of the levels of exudate production. The aim of this study was to
      identify a valid and reliable method of measuring wound exudate production per
      unit area of wound surface. METHOD: Two methods were tested. Method A measured
      the weight of exudate collected in dressings by 'before and after' weighing of
      all dressing materials that came into contact with wound exudate. Method B
      measured wound exudate collected as part of topical negative pressure (TNP)
      therapy. RESULTS: Method A: Complete data were collected on three patients (at
      which point the study was halted), but it was only possible to obtain accurate
      measurements for two of these. Exudate production was 0.10g/cm2/24 hours and
      0.21g/cm2/24 hours. It was time-consuming and required special equipment. Method
      B: Fifteen measurements from five patients were analysed and showed a mean
      exudate production of 1.3g/cm2/24 hours. CONCLUSION: There are problems with both
      methods of exudate measurement, but measuring wound fluid collected inTNP
      canisters seems simpler than weighing dressings and deserves further
      investigation.

PMID- 16620044
TI  - Salvage of infected dermal collagen implants with topical negative pressure
      therapy.

PMID- 16620045
TI  - Clinical efficacy of horsechestnut seed extract in the treatment of venous
      ulceration.
AB  - OBJECTIVE: To evaluate the clinical efficacy of orally administered horsechestnut
      seed extract in the treatment of venous leg ulcers. METHOD: In a prospective
      triple-blind randomised placebo-controlled trial, 54 patients with venous leg
      ulcers from a large South Australian community nursing service were randomly
      allocated to receive horsechestnut seed extract (n=27) or placebo (n=27) for 12
      weeks. Ulcers were assessed at weeks 0, 4, 8 and 12 utilising a wound assessment
      tool and the Alfred/Medseed Wound Imaging System. RESULTS: The difference between
      groups in the number of healed leg ulcers and change in wound surface area,
      depth, volume, pain and exudate was not statistically significant. However,
      horsechestnut seed extract did have a significant effect on the percentage of
      wound slough over time (RM-ANOVA F=2.76, p=0.045) and on the number of dressing
      changes at week 12 (t=-2.71, p=0.009). CONCLUSION: Even though horsechestnut seed
      extract is likely to attenuate the pathogenesis of venous insufficiency and, in
      turn, facilitate venous ulcer healing, the current study did not statistically
      support such a claim. However, taking into account the small sample and
      insufficient power of the trial, and the significant improvement in wound slough
      and visit frequency, it appears that it may be useful in the management of venous
      leg ulcers.

PMID- 16620046
TI  - Coordination and management of TNP from acute to primary care: overcoming the
      issues.

PMID- 16620047
TI  - Use of topical negative pressure to manage a complex wound with a vesicocutaneous
      fistula.

PMID- 16620048
TI  - Using the principle of hydrophobic interaction to bind and remove wound bacteria.

PMID- 16620049
TI  - Patients with locally advanced cervical cancer should not undergo routine
      pretreatment surgical staging.
AB  - The current FIGO staging system for locally advanced cervical cancer (Stages IIB
      to IVA) is considerably inaccurate, especially because lymph node metastases are
      ignored. Surgical staging has been used to overcome this insufficiency, allowing
      individualisation of therapy. However, this approach is controversial and should
      not be routinely undertaken considering the feasibility, adequacy and morbidity
      involved with the surgical procedure. Moreover, the survival benefit of surgical
      staging has yet to be proven and accurate non-invasive imaging alternatives, such
      as position emission tomography (PET) scanning, have become available. The
      management of patients with locally advanced cervical cancer based on PET and
      computed tomography (CT) imaging is proposed and discussed.

PMID- 16620050
TI  - Definitive and palliative radiotherapy for cervix cancer in the elderly.
AB  - The elderly population is increasing in number. Aggressive therapeutic
      intervention in this patient group may not always be possible because of age, the
      presence of co-morbidity, and poor functional status. Hence, individualized
      management of cervix cancer (CC) in the elderly is often practiced. Because of
      the preceding consideration, the cases of 79 women 65 years of age and older with
      CC treated with radiation over the last 20 years were reviewed. The cases were
      classified into two groups--those who were aggressively irradiated (group 1: 43
      patients) and those managed less intensively for palliation (group 2: 36
      patients). Local tumor control, complications, and survival were assessed. There
      were fewer extremely aged (> or = 75 years of age) women (p = 0.006) with
      advanced stage disease (p = 0.012) in group 1 than in group 2. Also, group 1
      women experienced fewer treatment failures (p < 0.0003) and more of them were
      alive and well at last follow-up (p < 0.005) than those from group 2. The median
      survival periods for groups 1 and 2 were 60 months and 11 months, respectively (p
      < 0.0001); the corresponding 5-year crude survival rates were 54% and 19%,
      respectively (p = 0.002). Two women required remedial surgery for bowel
      obstruction/perforation after irradiation, and one patient sustained chronic
      radiation cystitis.

PMID- 16620051
TI  - Improved survival of patients with ovarian cancer in Northern Denmark, 1985-2004.
AB  - OBJECTIVE: Ovarian cancer is a serious disease with a high mortality. Our aim was
      to examine changes in the survival of patients with ovarian cancer in Northern
      Denmark. STUDY DESIGN AND SETTING: Patients (no. = 3,719) with an incident
      discharge diagnosis of ovarian cancer (1985-2004) from any hospital in four
      Danish counties (population, 1.6 million) were included and tracked for mortality
      through the Danish Civil Registration System. We determined survival and
      mortality rates stratified by age, and used Cox proportional hazard regression
      analyses to assess changes over time. RESULTS: Overall survival rate improved
      between 1985 and 2004. One-year survival increased from 61% to 73%, and five-year
      survival from 30% to 38%. Compared with the period 1985-1989 the age-adjusted one
      year mortality rate ratio (MRR) was 0.65 (2000-2004) and the age-adjusted five
      year MRR was 0.80 (1995-1999). The improvement was most pronounced in patients
      older than 40 years. CONCLUSION: The survival of ovarian cancer patients has
      improved in Denmark in recent decades. This change may be the result of improved
      treatment.

PMID- 16620052
TI  - Actin bundling protein fascin expression in ovarian neoplasms: comparison of
      histopathologic features of tumors obtained by the first and secondary
      cytoreduction surgeries.
AB  - PURPOSE OF INVESTIGATION: The aim of the study was to compare the fascin
      expression pattern and histopathologic features of malign epithelial ovarian
      tumors obtained by the primary and secondary surgeries. METHODS: The samples of
      94 epithelial ovarian carcinomas, 35 secondary surgeries for ovarian carcinomas,
      13 borderline epithelial ovarian tumors, 25 cystadenomas and four normal ovarian
      tissues were stained by means of fascin immunohistochemistry. Secondary surgeries
      included in the study were secondary cytoreduction at the time of second-look
      laparotomy (SLL), interval debulking surgery after neoadjuvant chemotherapy or
      secondary cytoreductive surgery in patients with recurrent epithelial ovarian
      carcinoma. RESULTS: Mean rank value of the stromal fascin score was higher in 94
      cases of malign epithelial ovarian carcinomas than borderline epithelial tumors,
      cystadenomas and normal ovaries (.000, p < 0.001). There was no significant
      difference in terms of total epithelial fascin score (.685, p > 0.05) and total
      stromal fascin score (.572, p > 0.05) between the primary and the secondary
      surgeries of epithelial ovarian carcinomas. CONCLUSIONS: Regarding the results of
      stromal fascin expression in 94 epithelial ovarian carcinomas, we hypothesized
      that cell-matrix interaction was an important step in the progression of malign
      epithelial ovarian neoplasms. Our study showed that the initial tumorigenic
      phenotype did not change with time and use of cisplatinum-based combination
      chemotherapy. Further studies with close follow-up of patients are necessary to
      reveal the role of fascin on matrix degradation mechanisms which might be the
      cause of the recurrences in ovarian neoplasms.

PMID- 16620053
TI  - Angiopoietin-1, 2 and Tie2 expressions in endometrial adenocarcinoma--the Ang2
      dominant balance up-regulates tumor angiogenesis in the presence of VEGF.
AB  - We investigated Ang1, Ang2 and Tie2 expressions including balance and
      intratumoral vessels in the role of angiogenesis of endometrial adenocarcinoma.
      Immunohistochemical staining was performed on 133 patients with endometrial
      (endometrioid) adenocarcinoma, including 73 with G1, 34 with G2, and 26 with G3.
      The levels of Ang1, Ang2 and Tie2 expressions were expressed as staining score.
      Total vessel count (TVC), microvessel count (MVC) and mean vessel diameter (VD)
      in the CD34-stained tissues were measured in five hot spot areas at x 200
      magnification by image cytometry. These results were compared with high and low
      vascular endothelial growth factor (VEGF) expressions. Ang1, Ang2, Tie2 and CD34
      were expressed in the cytoplasm of tumor cells. A significant correlation was
      found among Ang1, Ang2 and Tie2 expressions. In high VEGF cases, Ang1 expression
      was correlated negatively with TVC and MVC, but positively with VD, and the Angl
      < Ang2 group was significantly higher in TVC and MVC and tended to be smaller in
      VD than the Ang1 > Ang2 group. VD was significantly larger in G3 than in G1. The
      Ang1 < Ang2 balance may be one of the key factors for angiogenesis of endometrial
      carcinoma in the presence of high VEGF expression.

PMID- 16620054
TI  - Prevalence of human papilloma virus infection of the uterine cervix in women with
      abnormal cervical cytology.
AB  - PURPOSE OF INVESTIGATION: To determine the prevalence of human papillomavirus
      (HPV) using polymerase chain reaction (PCR) in women with abnormal cytology
      results. METHODS: A prospective study of 215 women with abnormal cytology results
      referred consecutively to the cervical pathology clinic was carried out. A second
      cervical cytology using the Bethesda System was performed on all the patients to
      confirm the initial diagnosis, as well as to test for the presence of HPV by PCR
      and a colposcopy and punch biopsy in cases presenting with an abnormal pattern on
      colposcopy. The sensivitiy, specificity, and positive and negative predictive
      value (PPV and NPV) were calculated using 2 x 2 tables. RESULTS: The women aged
      35 years or younger presented a higher percentage of HPV infection (85.6%) than
      the women over 35 years of age (54%). The highest percentage of women with a
      positive result for HPV was found in those with a cytological high-grade squamous
      intraepithelial lesion (HSIL) (85.5%), as compared with 47.4% of the women with a
      cytological low-grade squamous intraepithelial lesion (LSIL). HPV infection has a
      high negative predictive value (93.2% of cases) and a high sensitivity (93.5%)
      for the detection of HSIL by biopsy, although the specificity and positive
      predictive value were low, 51.5% and 52.1%, respectively. CONCLUSION: Patients
      with cytological HSIL have a high prevalence of HPV infection.

PMID- 16620055
TI  - Is there a protective role of progestogens on the proliferation of human ovarian
      cancer cells in the presence of growth factors?
AB  - PURPOSE OF INVESTIGATION: The role of progestogens in the genesis of ovarian
      cancer remains unclear although a rather protective behaviour has been suggested.
      Epidemiological studies indicate a possible increase in the risk for combined
      estrogen/progestin as compared to estrogen alone. It is ambigious whether a
      difference exists within the various progestogens. Apart from sex steroids,
      growth factors play a crucial role in the genesis of ovarian cancer, although as
      yet little investigated. In the present study we have explored the effect of
      progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) on
      the proliferation of human ovarian cancer cells alone and in the presence of
      growth factors. METHODS: For the experiments human ovarian cancer cells (OVCAR-3)
      were used. The progestogens were tested at the concentrations of 0.01 to 10
      microM. The growth factor mixture consisted of EGF, FGF and IGF-I, each at a
      concentration of 10 pM. The incubation time was three or seven days.
      Proliferation rate was measured by an ATP-assay. RESULTS: After three days'
      incubation the growth factors induced an increase in the proliferation rate of
      about 50%. Progesterone alone did not show any significant change as compared to
      the control values, whereas NET and MPA elicited a significant increase at 1 and
      10 microM and at 1 microM, respectively. In the presence of growth factors none
      of the progestogens was able to inhibit the proliferative stimulation. After
      seven days' incubation the growth factors still showed an increase of about 50%.
      MPA alone had an inhibitory effect at 10 microM, for NET and P no effects were
      observed. Again in the presence of growth factors no progestogen was able to show
      an inhibitory effect. CONCLUSION: Our results indicate that progestogens do not
      have a protective role on the growth of pre-existing ovarian cancer cells, at
      least in the presence of growth factors. Further investigations are worthwile to
      evaluate possible differences between the effect of the various progestogens.

PMID- 16620056
TI  - Oxygenation status of primary and recurrent squamous cell carcinomas of the
      vulva.
AB  - INTRODUCTION: Cancers of the vulva are relatively rare and, therefore, little is
      known about the pathophysiological role of tumor oxygenation in this entity.
      METHODS: Data are presented on the oxygenation status of primary (n = 15) and
      recurrent (n = 19) cancers of the vulva, as measured by the Eppendorf pO2
      histography system. RESULTS: Contrary to other tumor entities, no significant
      differences in the oxygenation status between primary (median pO2 = 13 mmHg;
      hypoxic fraction < or = 5 mmHg = 37%) and recurrent (median pO2 = 11 mmHg;
      hypoxic fraction < or = 5 mmHg = 45%) tumors were found. Oxygenation was
      significantly lower in cancers of the vulva than in the subcutis. Anemic patients
      had significantly poorer tumor oxygenation compared with patients whose cHb
      values were within the normal range (p = 0.02). CONCLUSIONS: The oxygenation of
      vulvar cancers is similar to other tumor entities, but does not show more severe
      hypoxia in recurrent cases. Anemia is associated with a poorer oxygenation status
      in vulvar cancers, whereas in the normal tissue no impact of cHb values on the
      median pO2 was observed.

PMID- 16620057
TI  - The incidence of vulvar pathology and vulvectomy within risk and non-risk groups.
AB  - At the Institute of Gynecology and Obstetrics over a period of five years, more
      than 180,000 women were examined; 580 simple and 178 radical vulvectomies were
      performed.

PMID- 16620058
TI  - Survey of adjuvant hormone therapy in patients after endometrial stromal sarcoma.
AB  - INTRODUCTION: We surveyed the use of adjuvant hormonal therapy in patients with
      endometrial stromal sarcomas. MATERIAL AND METHODS: A questionnaire was
      circulated among the 130 members of an Internet-based endometrial stromal sarcoma
      support group. The questions pertained to age at diagnosis, organs involved at
      diagnosis, recurrences, metastases, current disease status, and treatment
      protocols, with special focus on hormonal therapy. RESULTS: The questionnaire was
      returned by 64 of 120 women (49%). At the time of the study 48 patients (mean
      follow-up 2.4 (range, 1-9) years) had no evidence of disease (NED) and 16 (mean
      follow-up 6.2 (range, 1-22) years) were alive with disease (AWD). Of the 16 women
      AWD, 15 (95%) were being treated with hormones as opposed to ten of 48 (21%)
      women with NED. Hormone treatment consisted of progestins (15 patients),
      aromatase inhibitors, aromatase inhibitor plus GnRH analog], or tamoxifen.
      DISCUSSION: Adjuvant hormonal therapy presently appears to be used predominantly
      in women with advanced or recurrent endometrial stromal sarcomas but is also a
      potential option for patients after surgery without residual tumor.

PMID- 16620059
TI  - Tissue and plasma carcinoembryonic antigen concentration in gynecologic
      malignancies.
AB  - In this study tissue and plasma concentrations were established in eight patients
      with gynecologic malignancies, and correlations between tissue and plasma CEA
      concentrations were compared. Tissue concentration was determined by the
      immunoperoxidase staining method. Plasma CEA concentration was lower than tissue
      concentration. The causes of this difference were examined in this study.

PMID- 16620060
TI  - A study of placental umbilical cord whole blood transfusion in 72 patients with
      anemia and emaciation in the background of cancer.
AB  - In the under-resourced world, transfusion to advanced oncological patients
      involves two major problems, i.e., (a) transfusion transmitted disease, and (b)
      infrastructural deficiency. Many hospitals cannot cope with the specialized
      requirements of immunocompromised cancer victims, for instance, leucoreduction,
      selective apheresis, irradiation of the blood, viral inactivation of the blood by
      solvent and/or detergent treatment or photochemical inactivation using psoralen
      or long wavelength ultraviolet light and cytomegalovirus safe blood. The
      exorbitant cost of red blood cell (RBC) substitutes like hemoglobin-based oxygen
      carriers or perflurocarbon emulsions, liposome encapsulated hemoglobin, is simply
      unacceptable for an average oncological patient in the developing world.
      Moreover, it should be underscored that none of the total blood functions are
      replaced by any available so-called blood substitute, the primary function of
      which is oxygen delivery and volume expansion only. A more accurate term should
      be red cell substitute. Cord blood, because of its rich mix of fetal and adult
      hemoglobin, platelet and white blood cell (WBC) count, and 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. In the present series,
      the collection of cord blood varied from 54 ml-128 ml, mean 82 ml +/- 7.6 ml SD;
      mean packed cell volume 48 +/- 4.1% SD; mean percent hemoglobin concentration
      16.4 g/dl +/- 1.6 g/dl SD. Not a single case of immunological or non
      immunological reaction has been encountered so far after transfusion of cord
      blood to cancer patients with percent of hemoglobin 8 g/dl or less. It appears
      that the medical fraternity can safely use this precious gift of nature-- which
      is free from infection, hypoantigenic with altered metabolic profile, filled with
      growth factors and cytokine-filled plasma, and has the potential of a higher
      oxygen carrying capacity than adult blood--as an emergency source of blood for
      the management of advanced cancer cases with anemia.

PMID- 16620061
TI  - Treatment of choriocarcinoma metastases by surgery and polychemotherapy - case
      report.
AB  - Choriocarcinoma is present in one out of every 40,000 pregnancies. There is a
      great risk for incidence of the disease in women who become pregnant after 45
      years of age. The clinical picture may vary and is related to the destruction of
      tissue and bleeding. New chemo protocols containing etoposide, cisplatin,
      ifosfamide, together with a resection of the focus resistant to chemotherapy,
      lead in most cases to the complete recovery.

PMID- 16620062
TI  - Preoperative breast ultrasound and Doppler velocimetric findings in patients with
      breast cancer.
AB  - PURPOSE: To evaluate the role of ultrasound and Doppler velocimetry in the
      diagnosis of breast cancer. METHODS: Thirty breast cancer patients, diagnosed by
      clinical examination, mammography and fine needle aspiration, or trucut biopsy
      were assessed by breast ultrasound including Doppler velocimetry to evaluate
      blood flow in the axillary and lateral thoracic arteries. Postoperative
      histopathological examination proved malignancy in all cases. This cohort was
      compared to another group of 30 patients with proven benign breast disease and a
      cross-matched control group of 30 asymptomatic women with no breast disease.
      RESULTS: In the 30 cancer patients, the size of masses ranged from 1-4 cm (2.51
      +/- 1.13), the mean axillary artery resistance index (RI) ranged from 0.8-0.88
      (0.84 +/- 0.03), and the lateral thoracic artery RI ranged from 0.45-0.59 (0.55
      +/- 0.106). However, power Doppler did not detect any increased perfusion. In the
      benign group, the lateral thoracic artery RI ranged from 0.78-0.86 (0.85 +/- 0.8)
      and the axillary artery RI ranged from 0.81-0.89 (0.81 +/- 0.05), while in the
      control group, the mean lateral thoracic artery RI ranged from 0.85 to 0.89 (0.87
      +/- 0.082), and the axillary artery RI ranged from 0.84-0.9 (0.88 +/- 0.16).
      Statistical analysis revealed only a high statistical significance (p < 0.01) for
      the lateral thoracic artery indices between the malignant group as compared to
      the benign and normal groups. There was no statistical significant difference in
      the axillary artery RI between the three groups. CONCLUSION: It is suggested that
      a marked decrease in the lateral thoracic artery RI with a cut-off value less
      than 0.6 is highly suggestive of malignancy. Taking the pilot nature of the
      results, further studies with much larger numbers are needed to corroborate such
      findings.

PMID- 16620063
TI  - Endometriosis mimicking soft tissue tumors: diagnosis and treatment.
AB  - The clinical manifestations, the radiologic appearance and the treatment of four
      women with extragenital endometriosis of the abdominal wall are presented. In two
      patients endometriosis was found adherent with the structures of the inguinal
      canal and in the other two the tumors infiltrated structures of the abdominal
      wall. Symptoms included cyclical pain and palpable subcutaneous masses fixed to
      the surrounding tissues. Computed tomography and magnetic resonance imaging
      failed to differentiate the lesions from other soft tissue tumors. Resection to
      healthy tissue margins is the treatment of choice, in order to avoid local
      recurrence.

PMID- 16620064
TI  - The role of actin bundling protein fascin in the progression of ovarian
      neoplasms.
AB  - PURPOSE OF INVESTIGATION: The aim of the study was to investigate the role of
      fascin in tumor progression and to investigate the role of fascin on endothelial
      cell migration and angiogenesis in ovarian neoplasms. METHODS: In the study, 94
      malign epithelial ovarian neoplasms, 13 borderline epithelial ovarian neoplasms,
      25 serous and mucinous cystadenomas and four normal ovarian tissues were examined
      by means of immunohistochemistry, using monoclonal antihuman fascin antibody,
      clone IM20. RESULTS: Total stromal fascin score in cases of borderline and malign
      epithelial ovarian tumors was significantly higher compared to normal ovaries and
      benign epithelial ovarian tumors (.000, p < 0.001). There was no statistically
      significant difference in terms of total epithelial fascin scores of samples
      between groups (.080, p > 0.05). Presence of vascular invasion (.000, p < 0.001),
      psammomatous calcifications (.001, p = 0.001), and lymphocytic infiltration
      (.000, p < 0.001) were significantly higher in malign neoplasms. There was no
      significant difference in terms of mean microvessel count and homogeneous or
      heterogeneous fascin expression of microvessels between the benign and malign
      groups (respectively p = .228 and p = .143). CONCLUSIONS: This study suggests
      that up-regulation of fascin in tumoral tissue may promote invasion of ovarian
      carcinoma by cell-matrix adhesion.

PMID- 16620065
TI  - Does raloxifene therapy affect mammographic breast cancer screening in
      postmenopausal patients?
AB  - OBJECTIVE: The aim of the study was to determine mammographic breast density
      changes during raloxifene therapy in postmenopausal patients MATERIALS AND
      METHODS: Fifty-five cases who were using raloxifen therapy were included in this
      retrospective analysis. Raloxifene was given for osteopenia and osteoporosis
      according to low bone mineral density measured by dual-energy X-ray
      absorptiometry (DEXA). None of the patients were using hormone replacement
      therapy 12 months before the initiation of raloxifene treatment or during the
      study. Mammographic breast density was determined by mammography before the
      initiation of raloxifene treatment (baseline) and after 12 to 16 months of
      therapy. The Breast Imaging Reporting and Data System (BI-RADS) breast density
      score was used for the evaluation of mammographic density. RESULTS: There was no
      change in mammographic breast density when the baseline and the first mammography
      taken after the initiation of therapy were compared (p = 0.32). There was no
      significant correlation between the duration of raloxifene treatment and
      mammographic density measured after raloxifene treatment (r = -0.158, p = 0.25).
      Only in one patient did the BI-RADS classification of 2 change to 3 after 12
      months of therapy. CONCLUSIONS: In conclusion, raloxifene therapy for 12 to 16
      months does not increase mammographic breast density in postmenopausal women with
      low bone mass.

PMID- 16620066
TI  - Gynecologic problems among elderly women in comparison with women aged between 45
      64 years.
AB  - BACKGROUND: As women age, they face a variety of co-morbid medical problems as
      well as gynecologic problems that may differ from those of younger women.
      Clinicians should know how to screen and manage those problems among elderly
      women. OBJECTIVE: With this background, the study was designed to assess the
      gynecologic problems on admission among elderly women and women aged between 45
      64 years. METHODS: A retrospective analysis of symptom distribution of 200 women
      aged over 65 years and 200 women aged between 45-64 years from January 1999 to
      December 2003 was performed in an university clinic. PARTICIPANTS: Geriatric
      women and women aged between 45-64 years with gynecologic complaints on admission
      to outpatient clinics between January 1999 and December 2003. Analyses of
      demographic data and data related to symptom distribution, using appropriate
      parametric and non-paramertic statistical tests, were performed. RESULTS:
      Geriatric women had a higher number of pregnancies (p < 0.01) but lower
      percentage of hormone replacement therapy use (p < 0.1) compared to women aged 45
      64 years. No significant difference was observed in terms of the age at
      menopause. Vaginal fullness was felt most commonly by elderly women (p < 0.01) in
      contrast to menopausal vasomotor symptoms which were relevant in the younger age
      group (p < 0.01). As a clinical diagnosis, pelvic relaxation with uterine
      prolapse and genital malignancies were the common two diagnoses among geriatric
      women (p < 0.05). Postmenopausal vaginal bleeeding was observed more often among
      geriatric women compared to women aged 45-64 years (19.5% vs 12%, p = 0.03).
      Endometrial and ovarian cancer distribution did not differ among the two groups
      when the initial complaint was postmenopausal bleeding. CONCLUSION: Type and
      management of gynecologic problems in women aged over 65 can be challenging and
      differ from those for younger women. Thus, caring for these women in their
      reproductive years as well as in later life should be an aim for all obstetrician
      gynecologists.

PMID- 16620068
TI  - Retroperitoneal schwannoma presenting as an ovarian tumor.
AB  - A mass in the left annexal zone was discovered in a 56-year-old woman at the
      Department of General Surgery and was diagnosed as ovarian cancer. After the
      operation the mass appeared histologically to be retroperitoneal leyiomiosarcoma
      and because of residual disease, confirmed by computed tomography (CT) and
      nuclear magnetic resonance (NMR), complementary radiotherapy was carried out.
      Restaging supported the persistence of the tumor and so a second laparotomy was
      performed with complete tumor resection; the pathologic diagnosis was
      retroperitoneal benign schwannoma. The importance of careful preoperative
      imaging, such as echography, CT, NMR, arteriography and urography should be
      stressed for a correct clinical and surgical approach. Moreover, considering that
      in some selected clinical cases these tumors could be confused with others
      deriving from contiguous organs and structures, a different surgical approach may
      be needed together with dedicated and expert surgeons.

PMID- 16620067
TI  - Histopathologic correlation of dilatation and currettage and hysterectomy
      specimens in patients with postmenopausal bleeding.
AB  - PURPOSE OF INVESTIGATION: To evaluate the consistency of preoperative and
      postoperative histopathological findings in postmenopausal patients with abnormal
      bleeding. METHODS: Pathologic diagnoses of 42 postmenopausal women with abnormal
      bleeding or increased endometrial thickness who underwent both dilatation and
      curettage (D and C), and hysterectomy for proper indications were retrospectively
      examined. RESULTS: The most common diagnosis was irregular proliferative
      endometrium in both the pre- and postoperative groups with 16 patients each
      (38%). After subgroup analysis, 50% of the patients with a preoperative diagnosis
      of complex hyperplasia without atypia, had complex atypical hyperplasia, and two
      thirds of the patients with a preoperative diagnosis of complex atypical
      hyperplasia had endometrial cancer as the final diagnoses. CONCLUSION:
      Preoperative D and C endometrial pathology findings positively correlated with
      postoperative hysterectomy pathology results. However, as the real pathology gets
      worse , D and C seems to under-diagnose the real pathology. In cases with complex
      hyperplasia with or without atypia , a second D and C or hysteroscopic evaluation
      may be recommended.

PMID- 16620069
TI  - Aggressive angiomyxoma of the vulva: our experience of a rare case with review of
      the literature.
AB  - Aggressive angiomyxoma is a rare, benign but locally aggressive mesenchymal
      neoplasm, which occurs almost exclusively during the reproductive years of women.
      A 28-year-old woman developed an aggressive angiomyxoma within the left labium
      minus of the vulva. The tumor was excised, but the lesion was expanded to the
      surgical margins. Microscopically, sections showed many walled vessels of various
      sizes, a loose myxoid and collagenous stroma and stellate and spindle-shaped
      neoplasmatic cells. Immunohistochemically, the neoplasmatic cells showed strong
      positivity for vimentin and desmin and moderate positivity for CD34 and estrogen
      receptors. In conclusion, aggressive angiomyxoma of the vulva should be
      distinguished from the benign and malignant myxoid tumors or tumor-like
      conditions of vulva. The pathologic and immunohistochemic characteristics, the
      difficulties in determining the surgical margins and the treatment of this tumor
      are discussed. Also, the international literature is reviewed.

PMID- 16620070
TI  - Cervical cancer and low-risk HPV; a case report.
AB  - A case of cervical cancer in a 32-year-old woman with a genotype 6 HPV genital
      infection that developed from a cervical low-grade SIL after a LLETZ procedure
      two years before is presented. This case obliges us to reconsider both the benign
      nature of low-grade lesions and the potentially good prognosis of low-risk HPV
      infection.

PMID- 16620071
TI  - Ovarian hemangioma with elevated CA125 and ascites mimicking ovarian cancer.
AB  - We report a case of a very rare tumor of the ovary with an unusual presentation;
      an ovarian hemangioma with massive ascites and elevated CA125. A 57-year-old
      woman presenting with elevated CA125, massive ascites and a left solid adnexal
      mass of 60 x 47 mm, with calcification and increased blood flow at Doppler
      examination, was submitted to laparotomy. Frozen section was inconclusive and a
      staging procedure which complicated the patient was performed. Pathologic
      examination revealed cavernous hemangioma which is an extremely rare tumor of the
      ovary. Although it is very unusual, an ovarian hemangioma may present with
      ascites and elevated CA125 and the differential diagnosis from ovarian cancer
      should be considered.

PMID- 16620072
TI  - A case of primary peritoneal serous papillary carcinoma initially presented by
      massive bilateral pleural effusions.
AB  - Primary peritoneal serous papillary carcinoma (PSPC) is a rare primary peritoneal
      tumor. Clinically, PSPC usually presents with general abdominal discomfort
      resulting from variable amounts of ascites. In a state of small amounts of
      ascites, initial manifestation of massive bilateral pleural effusion is unusual.
      A 76-year-old female nonsmoker with no asbestos exposure complained of dyspnea
      during exercise. Chest radiograph showed a massive bilateral pleural effusion.
      Chest computed tomography (CT) revealed irregular pleural thickening and a small
      amount of ascites. Abdominopelvic CT revealed nodular thickening of the parietal
      peritoneum, mesenteric or omental nodules, omental cake, and lymphadenopathy in
      paraaortic regions. Adenocarcinoma cells were found via cytologic examination in
      bilateral pleural fluids and ascites. Because the primary site of the
      adenocarcinoma was not found, a surgical biopsy of the right pleural thickening
      was performed. The final diagnosis was PSPC. The patient was treated with
      platinum-based chemotherapy. Physicians should be aware of a possibility of PSPC
      when the radiographic findings show massive bilateral pleural effusion due to
      pleural carcinomatosis, with high serum levels of CA125.

PMID- 16620073
TI  - Well differentiated mesothelioma complicating endometrial carcinoma; a case
      report.
AB  - Peritoneal mesothelioma is a rare cancer of the abdominal cavity which has low
      malignant potential. Peritoneal mesothelioma can mimic other types of gynecologic
      malignancies. Careful clinical and pathologic evaluation is essential for an
      accurate diagnosis and treatment.

PMID- 16620074
TI  - Vaginal malignant melanoma in a healthy pregnancy--a case report.
AB  - Vaginal melanomas account for fewer than 2% of vaginal malignancies. The mean age
      at diagnosis is 55 years and the prognosis is poor, with an overall 5-year
      survival rate of 5% to 10%.

PMID- 16620075
TI  - CMF with 5-FU in continuous infusion--a pilot study.

PMID- 16620076
TI  - Synthesis and hydrogenation of bis(imino)pyridine iron imides.
AB  - Treatment of the iron bis(dinitrogen) complex, (iPrPDI)Fe(N2)2 (iPrPDI = (2,6
      iPr2C6H3N=CMe)2C5H3N), with a series of aryl azides resulted in loss of 3 equiv
      of N2 and formation of the corresponding four-coordinate iron imide compounds,
      (iPrPDI)Fe(NAr). These complexes, two of which (Ar = 2,6-iPr2-C6H3 and 2,4,6-Me3
      C6H2) have been characterized by X-ray diffraction, are significantly distorted
      from planarity. The metrical parameters in combination with Mossbauer
      spectroscopic and SQUID magnetic data suggest an intermediate spin iron(III)
      center antiferromagnetically coupled to a ligand-centered radical. Nitrene group
      transfer has been accomplished by addition of 1 atm of CO, yielding aryl
      isocyanates, ArNCO, and (iPrPDI)Fe(CO)2. Hydrogenation of the more sterically
      hindered members of the series furnished free aniline and the previously reported
      iron dihydrogen complex. Catalytic aryl azide hydrogenation has also been
      achieved, and the observed relative rates are consistent with N-H bond formation
      as the rate-determining step in aniline formation.

PMID- 16620078
TI  - Can the disproportion of oxidation state III be favored in RuII-OH2/RuIV=O
      systems?
AB  - Three new Ru-aqua complexes containing a mixed carbene and pyridylic ligands with
      general formulas [Ru(CNC)(bpy)(H2O)](PF6)2 (1) (CNC is 2,6-bis(butylimidazol-2
      ylidene)pyridine; bpy is 2,2'-bipyridine) and cis-/trans-[Ru(CNC)(nBu
      CN)(H2O)](PF6)2 (cis-2 and trans-2) (nBu-CN is 2-(butylimidazol-2
      ylidene)pyridine) have been prepared and structurally characterized both in the
      solid state (monocrystal X-ray diffraction analysis for 1 and for the related
      complex trans-[Ru(Br)(CNC)(nBu-CN)](PF6)) and in solution (for all of them)
      through NMR. The electrochemical properties of these three Ru-aqua complexes have
      been investigated by cyclic voltammetry, differential pulse voltammetry and
      Coulombimetric techniques. It is found that, for complex 1 at pH 7, the
      difference between the IV/III and the III/II redox couples (DeltaE1/2) is 50 mV,
      which is the smallest ever reported for this type of complex. On the other hand,
      for complexes cis-2 and trans-2, the oxidation state III is unstable with respect
      to disproportionation to II and IV. The reactivity of their Ru=O species has been
      tested toward cis-beta-methylstyrene oxidation, and it has been compared to
      [Ru(O)(trpy)(bpy)]2+. An inverse correlation between the degree of cis/trans
      epoxide isomerization and DeltaE1/2 is found. In particular, for complexes cis-2
      and trans-2, which have a DeltaE1/2 < 0, the epoxidation is highly
      stereoselective, yielding only cis-epoxide.

PMID- 16620077
TI  - Responsive periodic mesoporous polydiacetylene/silica nanocomposites.
AB  - Responsive PMO materials have been synthesized through co-assembly of bridged
      diacetylenic silsesquioxane and surfactant. The spatially defined
      polydiacetylenic component, mesoporous network, and the covalent proximity of
      polydiacetylene to silica endow the PMO with mechanical robustness, reversible
      chromatic responses, improved thermal stability, and faster responses to chemical
      stimuli. This research also provides an efficient molecular design and assembly
      paradigm to fabricate a family of conjugated optoelectronic materials, creating
      novel platforms for sensors, actuators, and other device applications.

PMID- 16620079
TI  - High-field NMR studies of molecular recognition and structure-function
      relationships in antimicrobial piscidins at the water-lipid bilayer interface.
AB  - High magnetic field solid-state NMR was performed on amphipathic cationic
      antimicrobial peptides from fish to characterize their secondary structure and
      orientation in hydrated phospholipid bilayers. High-resolution distance and
      orientational restraints on 13C- and 15N-labeled amidated piscidins 1 and 3
      provided site-specific information establishing alpha-helicity and an orientation
      parallel to the membrane surface. Few membrane-bound natural peptides with this
      topology have been structurally studied at high resolution in the presence of
      hydrated lipid bilayers. This orientation was foreseen since the partitioning of
      amphipathic cationic antimicrobial peptides at the water-bilayer interface allows
      for favorable peptide-lipid interactions, and it may be related to the mechanism
      of action. The enhanced resolution obtained at 900 MHz evidences a determinant
      advantage of ultra-high-field NMR for the structural determination of multiple
      labeled peptides and proteins.

PMID- 16620080
TI  - Design, synthesis and X-ray structure of protein-ligand complexes: important
      insight into selectivity of memapsin 2 (beta-secretase) inhibitors.
AB  - Structure-based design, synthesis, and X-ray structure of protein-ligand
      complexes of memapsin 2 are described. The inhibitors are designed specifically
      to interact with S2- and S3-active site residues to provide selectivity over
      memapsin 1 and cathepsin D. Inhibitor 6 has exhibited exceedingly potent
      inhibitory activity against memapsin 2 and selectivity over memapsin 1 (>3800
      fold) and cathepsin D (>2500-fold). A protein-ligand crystal structure revealed
      cooperative interactions in the S2- and S3-active sites of memapsin 2. These
      interactions may serve as an important guide to design selectivity over memapsin
      1 and cathepsin D.

PMID- 16620081
TI  - Tandem Nazarov cyclization-michael addition sequence catalyzed by an Ir(III)
      complex.
AB  - The first examples of a tandem Nazarov cyclization/Michael addition process are
      described. The sequence is efficiently catalyzed by Ir[Me(CO)(dppe)(DIB)]2+ and
      occurs with high diastereoselectivity, creating three contiguous stereocenters.
      The mechanistic factors controlling the reactivity and diastereoselectivity are
      discussed.

PMID- 16620082
TI  - Expanded capsules with reversibly added spacers.
AB  - Glycolurils insert as spacer elements in a capsule to create a new space with
      enhanced dimensions.

PMID- 16620083
TI  - Synthesis of mesoporous carbon materials via enhanced hydrogen-bonding
      interaction.
AB  - A general method based on two-phase polymerization has been described to
      synthesize mesoporous carbons via self-assembly. Mild reacting conditions and
      wide composition ranges are the obvious advantages of this method over the
      techniques previously reported.

PMID- 16620084
TI  - Reflection symmetry breaking in achiral rod-shaped smectic liquid crystals?
AB  - The SmC phase of 4'-octyloxyphenyl-4-octyloxybenzoate has been examined in light
      of recent reports that this phase is chiral. The results suggest that two
      varieties of chiral domains in LC cells of the phenylbenzoate are indeed formed,
      driven by interactions with surfaces. Application of sensitive probes for
      chirality and polarity in the absence of such interfacial influences failed to
      find any. Currently, there is no evidence that the subject SmC phase is chiral.

PMID- 16620085
TI  - Photoinduced magnetization with a high curie temperature and a large coercive
      field in a cyano-bridged cobalt-tungstate bimetallic assembly.
AB  - A three-dimensional magnetic material
      [{CoII(pyrimidine)(H2O)}2{CoII(H2O)2}{WV(CN)8}2](pyrimidine)2. 2H2O is prepared.
      This compound exhibits a charge-transfer-induced spin transition with a large
      thermal hysteresis loop of 90 K. Irradiating with light causes the low
      temperature phase to exhibit a spontaneous magnetization with a Curie temperature
      of 40 K and a magnetic hysteresis loop with a coercive field of 12 000 G, which
      is the highest value reported for a photomagnet. The observed photoinduced
      magnetization is due to the charge-transfer phase transition from the {CoIIhs(S =
      3/2)}{CoIIIls(S = 0)}2-NC-{WIV(S = 0)}2 phase to the {CoIIhs(S = 3/2)}3-NC-{WV(S
      = 1/2)}2 phase by the irradiation.

PMID- 16620086
TI  - Design of effective zeolite catalysts for the complete hydrogenation of CO2.
AB  - Ab initio molecular orbital calculations have been applied to the study of the
      three-stage zeolite-catalyzed hydrogenation of CO2 to methanol. The results
      present strong evidence that appropriate chemical modifications to ZSM-5 can lead
      to significantly lower energy barriers for the three component reactions, that
      is, hydrogenation of CO2, HCO2H, and CH2O. Zeolites incorporating either Na+ or
      Ge are more effective catalysts than conventional acidic zeolites for the
      hydrogenation of CO2 to give HCO2H, but amine-based zeolites do not lead to
      significantly lower barriers for any of the three hydrogenation reactions.
      However, we predict that when all three features, namely, Na+, N, and Ge, are
      incorporated in the zeolite, there is a dramatic improvement in catalytic
      activity for all three reactions.

PMID- 16620087
TI  - Quantum-dot-based nanosensor for RRE IIB RNA-Rev peptide interaction assay.
AB  - Rev is an important HIV-1 regulatory protein that binds the Rev responsive
      element (RRE) within the env gene of HIV-1 RNA genome; the binding of Rev to RRE
      is essential for the expression of the structural genes, gag-pol and env, and for
      HIV replication. Here we report a quantum-dot (QD)-based nanosensor that can be
      used in fluorescence resonance energy transfer (FRET) assays of RRE IIB RNA-Rev
      peptide interactions. In comparison with conventional fluorescent dye-based
      methods, this QD-based nanosensor offers the distinct advantages of not
      inhibiting the Rev-RRE interaction, high sensitivity, improved accuracy, and
      simultaneous FRET-related two-parameter detection. This QD-based nanosensor
      provides a new approach to study the effects of inhibitors upon Rev-RRE
      interaction, and it may have a wide applicability in the development of new drugs
      against HIV-1 infection.

PMID- 16620088
TI  - Highly reversible and multi-stage cantilever actuation driven by polyelectrolyte
      brushes.
AB  - Microcantilever bending can be reversibly driven by conformational changes of
      phosphate containing polyelectrolyte brushes when exposed to different pH or salt
      solutions. The deflection of the cantilevers allows a detailed analysis of the
      properties of polymer brushes, while these systems are also a first step toward
      polymer-based nanoactuators.

PMID- 16620089
TI  - A polyaromatic receptor with an ethereal fence that directs K+ for effective
      cation-pi interaction.
AB  - We have designed and synthesized a HAB-based receptor with six ethereal oxygens
      on one face of the central benzene ring by a trimerization of a diarylacetylene
      in which the ethereal oxygens are tied together with a tetramethylene bridge.
      This unique amphiphilic receptor allows an efficient binding of a single
      potassium cation by a synergistic interaction with the polar ethereal fence and
      with the central benzene ring via cation-pi interaction. Furthermore, the ready
      accessibility of this unique receptor with a bipolar binding pocket will allow
      the exploration of its usage for developing efficient sensing devices for various
      metal cations.

PMID- 16620090
TI  - Force-induced insulin dimer dissociation: a molecular dynamics study.
AB  - Understanding the forces and dynamics of insulin dissociation is critical for
      devising formulations for the treatment of insulin-dependent diabetes. In earlier
      work, we applied AFM-based force spectroscopy to covalently tethered and oriented
      insulin monomers to assess the effect of molecular orientation on insulin-insulin
      binding forces. We report here on steered molecular dynamics simulations of the
      insulin dissociation force spectroscopy experiment. Consistent with our
      experiments, our simulation results suggest that insulin dimer dissociation
      occurs near the limit of extensibility of the B-chain. We have also found that
      the forced dissociation of the insulin dimer is a rate-dependent process,
      involving significant conformational changes to the monomer(s). The insulin dimer
      dissociation pathway also depends on the relative strength of the inter-monomer
      interactions across the antiparallel beta-sheet interface and the intra-monomer
      interactions of residues A1 and A30 with the insulin B-chain. Our simulation
      results strongly support the design of bioactive insulin analogues that involves
      altering hydrogen bonding and hydrophobic interactions across the beta-sheet
      dimer interface.

PMID- 16620091
TI  - Pseudotetrahedral polyhalocubanes: synthesis, structures, and parity violating
      energy differences.
AB  - All possible pseudotetrahedral, stable polyhalocubanes were prepared, and their
      structures were proven by NMR spectroscopy and X-ray crystallography. Parity
      violating energy differences (DeltaEpv) and vibrational frequency shifts were
      computed. The DeltaEpv values are predicted to be one to two orders of magnitude
      smaller than those for the corresponding polyhalomethanes. However, the DeltaEpv
      energy ordering is the same as that for the methane analogues. For both substance
      classes, the (S) isomers are, with the exception of the bromochlorofluoroiodo
      derivatives, more stable than the (R) forms.

PMID- 16620092
TI  - Synthesis and structure of a nucleoside with pi-conjugated nitroxide spin label
      forming a one-dimensional ferromagnetic chain.
AB  - Spin labeled 2'-deoxyuridine, in which a significant fraction of the spin density
      is delocalized from a nitroxide radical to the DNA base residue, was prepared as
      a crystalline solid, stable at ambient conditions. The crystal packing, which
      includes multiple hydrogen bonds, leads to one-dimensional chains of molecules
      with predominant intrachain ferromagnetic coupling and weaker interchain
      antiferromagnetic coupling.

PMID- 16620093
TI  - A nanoring-nanosphere molecule, {Mo214V30}: pushing the boundaries of
      controllable inorganic structural organization at the molecular level.
AB  - A controlled, Raman-monitored chemical reduction of a molybdate and vanadate
      mixture affords a new type of molybdenum-oxide-based cluster showing an
      unprecedented level of inorganic structural organization. The cluster
      incorporates two nanosized substructures (a ring and a sphere) in an open clam
      like assembly. Multiple methods indicate that the nanoring contains delocalized
      electrons and the nanosphere contains localized but interacting electrons.

PMID- 16620094
TI  - Rhodium-catalyzed tandem vinylcyclopropanation of strained alkenes.
AB  - This communication reports an unusual rhodium-catalyzed 1,6-addition of a
      dienylboronate ester to highly strained alkenes. The resulting vinylcyclopropane
      fused tricyclic products were produced in moderate to good yields. Preliminary
      mechanistic studies are also presented.

PMID- 16620095
TI  - Total synthesis of (-)-dictyostatin.
AB  - A convergent total synthesis of dictyostatin is described. Key features of the
      synthesis include the use of titanium-mediated cyclizations of (silyloxy)enynes
      for the synthesis of stereotriads, a subunit coupling by metathesis, and
      macrocyclization by intramolecular Horner-Wadsworth-Emmons olefination.

PMID- 16620096
TI  - Butterfly diradical intermediates in photochemical reactions of Fe2(CO)6(mu-S2).
AB  - Photolysis of the tetrahedrane Fe2(CO)6(mu-S2) at 450 +/- 35 nm in a Nujol matrix
      at low temperatures gives an isomer characterized by its nu(CO) infrared
      frequencies. Comparison of these experimental frequencies with those calculated
      by density functional theory using the BP86 functional indicates this photoisomer
      to be the butterfly singlet diradical Fe2(CO)6S2 isomer in which the S-S bond of
      the tetrahedrane is broken but the Fe-Fe bond is retained. Photolysis at higher
      energies (420-280 nm) results in CO loss from this singlet butterfly diradical as
      indicated again by comparison of the experimental infrared nu(CO) frequencies
      with those calculated for an Fe2(CO)5S2 isomer of this type.

PMID- 16620097
TI  - Tuning the coordination number of hydroxypyridonate-based gadolinium complexes:
      implications for MRI contrast agents.
AB  - Eight-coordinate hydroxypyridinone/terephthalamide GdIII complexes display high
      relaxivities due to their two inner sphere water molecules. This relaxivity can
      be further increased by functionalizing the terephthalamide moiety with an amine.
      A significant hydrogen bonding interaction between the amine and another water
      molecule close to the GdIII apparently facilitates its coordination on the open
      site of the metal. The resulting nine-coordinate complex has three inner sphere
      water molecules, while maintaining high stability and fast ligand exchange rates.

PMID- 16620098
TI  - One-electron oxidation of DNA oligomers that lack guanine: reaction and strand
      cleavage at remote thymines by long-distance radical cation hopping.
AB  - The anthraquinone (AQ) photosensitized one-electron oxidation of DNA introduces a
      radical cation (electron "hole") that migrates through the duplex by hopping. The
      radical cation normally is trapped irreversibly by reaction at guanine. We
      constructed AQ-linked DNA oligomers composed exclusively of A/T base pairs. Their
      irradiation led to reaction and strand cleavage primarily at thymines. Long
      distance radical cation hopping to distant thymines was demonstrated by the
      distance dependence of the process and by experiments with DNA oligomers that
      contain a single remote GG step. The reaction of the radical cation at thymine
      was shown to involve its 5-methyl group by the replacement of selected thymines
      with uracils. These findings show that the reactivity of radical cations in DNA
      cannot be explained simply by exclusive reliance on the relative oxidation
      potential of the nucleobases. Instead, the site of reaction is determined in
      accord with the Curtin-Hammett principle for reactive species in rapid
      equilibrium.

PMID- 16620099
TI  - Dimerization of cyclopropyl ketones and crossed reactions of cyclopropyl ketones
      with enones as an entry to five-membered rings.
AB  - An unexpected dimerization of cyclopropyl ketones was observed, and analysis of
      the reaction pathway led to development of a synthetically useful crossed
      reaction between cyclopropyl ketones and enones to afford densely functionalized
      cyclopentane products.

PMID- 16620100
TI  - Formation of nickeladihydropyran by oxidative addition of cyclopropyl ketone. Key
      intermediate in nickel-catalyzed cycloaddition.
AB  - Cyclopropyl phenyl ketone underwent oxidative addition to Ni(PCy3) generated from
      Ni(cod)2 and PCy3 to give a nickeladihydropyran, which is a key intermediate for
      the Ni(0)-catalyzed homo- or heterocycloaddition to give cyclopentane compounds
      having two carbonyl substituents at the 1,3-position.

PMID- 16620101
TI  - Selective shortening of single-crystalline gold nanorods by mild oxidation.
AB  - Gold nanorods (NRs) have received much attention due to their size-dependent
      surface plasmon-related optical properties. A seed-mediated approach has recently
      been developed for the synthesis of Au NRs with varying length-to-diameter aspect
      ratios. With the introduction of silver ions in the growth solution, Au NRs of
      narrow size distributions can be produced in high yields. Herein we describe an
      approach for the continuous and selective shortening of Au NRs synthesized by the
      silver ion-assisted seed-mediated method through oxidation with environmentally
      benign oxygen at slightly elevated temperatures. UV-visible extinction
      measurements indicate that the longitudinal surface plasmon band of Au NRs
      decreases in intensity and blue-shifts as a function of the oxidation time.
      Transmission electron microscopy (TEM) imaging shows that the length of Au NRs
      decreases with oxidation and their diameter stays almost constant, which suggests
      that oxidation starts at the ends of Au NRs. The size distributions of shortened
      Au NRs are similar to those of starting NRs. Further oxidation transforms Au NRs
      into nanospheres, which become smaller in diameter and finally completely
      disappear. It has been found that the oxidation rate of Au NRs can be controlled
      by temperature and acid concentration. Furthermore, high-resolution TEM studies
      reveal that Au NRs synthesized by the silver ion-assisted seed-mediated method
      are single crystalline and they stay single crystalline during oxidation. It is
      expected that Au NRs of any aspect ratio with narrow size distributions within
      the limit of that possessed by starting NRs can be produced by this mild
      oxidation approach.

PMID- 16620102
TI  - Rhodium(I)-catalyzed [4+2+2] cycloadditions of 1,3-dienes, alkenes, and alkynes
      for the synthesis of cyclooctadienes.
AB  - The first [4+2+2] cycloadditions involving terminal alkynes and diene-enes,
      including a fully intramolecular example, are reported resulting in the formation
      of cyclooctadienes using [RhCl(CO)2]2 (5 mol %) treated with AgSbF6 (10 mol %) as
      a precatalyst. The reaction is general for a variety of terminal alkynes, as well
      as variously substituted diene-enes (yields up to 88%).

PMID- 16620103
TI  - Development of the 1,2-oxaza-Cope rearrangement.
AB  - A method for a concise assembly of oxazine rings based on a Lewis acid-promoted
      hetero-Cope rearrangement is described. The hetero-Cope rearrangement features
      the first examples of the [3,3]-sigmatropic transpositions involving the nitroso
      group. A variety of functionalized substrates have been subjected to the
      reaction. The described method has a strong potential for the synthesis of marine
      natural products containing oxazine rings.

PMID- 16620104
TI  - Free-radical version of the strecker synthesis of alpha-aminoamides promoted by
      aqueous H2O2/TiCl3/HCONH2 system.
AB  - A new reaction of general synthetic interest representing the free-radical
      version of the Strecker synthesis to alpha-aminoamides is reported. A hydroxy
      radical, generated by Ti(III) one-electron reduction of H2O2, abstracts a H atom
      from the C-H bond of formamide, and the resulting carbamoyl radical adds to the C
      atom of aldimines formed in situ, leading to a one-pot synthesis of alpha
      aminoamides. Several types of aldehydes can participate in this process.

PMID- 16620105
TI  - Amino alcohols as ligands for nickel-catalyzed suzuki reactions of unactivated
      alkyl halides, including secondary alkyl chlorides, with arylboronic acids.
AB  - Suzuki cross-coupling reactions of an unprecedented array of unactivated primary
      and secondary alkyl halides (including challenging alkyl chlorides) can be
      accomplished through the use of nickel/amino alcohol-based catalysts. Both the
      nickel precatalyst and the amino alcohols (prolinol or trans-2-aminocyclohexanol)
      are commercially available and air-stable. In view of the remarkable diversity of
      amino alcohols that are readily accessible, this discovery may open the door to
      the rapid development of versatile catalysts for a wide range of cross-coupling
      processes.

PMID- 16620107
TI  - A solid-state NMR study of the dynamics and interactions of phenylalanine rings
      in a statherin fragment bound to hydroxyapatite crystals.
AB  - Extracellular matrix proteins regulate hard tissue growth by acting as adhesion
      sites for cells, by triggering cell signaling pathways, and by directly
      regulating the primary and/or secondary crystallization of hydroxyapatite, the
      mineral component of bone and teeth. Despite the key role that these proteins
      play in the regulation of hard tissue growth in humans, the exact mechanism used
      by these proteins to recognize mineral surfaces is poorly understood.
      Interactions between mineral surfaces and proteins very likely involve specific
      contacts between the lattice and the protein side chains, so elucidation of the
      nature of interactions between protein side chains and their corresponding
      inorganic mineral surfaces will provide insight into the recognition and
      regulation of hard tissue growth. Isotropic chemical shifts, chemical shift
      anisotropies (CSAs), NMR line-width information, (13)C rotating frame relaxation
      measurements, as well as direct detection of correlations between (13)C spins on
      protein side chains and (31)P spins in the crystal surface with REDOR NMR show
      that, in the peptide fragment derived from the N-terminal 15 amino acids of
      salivary statherin (i.e., SN-15), the side chain of the phenylalanine nearest the
      C-terminus of the peptide (F14) is dynamically constrained and oriented near the
      surface, whereas the side chain of the phenylalanine located nearest to the
      peptide's N-terminus (F7) is more mobile and is oriented away from the
      hydroxyapatite surface. The relative dynamics and proximities of F7 and F14 to
      the surface together with prior data obtained for the side chain of SN-15's
      unique lysine (i.e., K6) were used to construct a new picture for the structure
      of the surface-bound peptide and its orientation to the crystal surface.

PMID- 16620106
TI  - Nickel-catalyzed, carbonyl-ene-type reactions: selective for alpha olefins and
      more efficient with electron-rich aldehydes.
AB  - Described are several classes of unusual or unprecedented carbonyl-ene-type
      reactions, including those between alpha olefins and aromatic aldehydes.
      Catalyzed by nickel, these processes complement existing Lewis acid-catalyzed
      methods in several respects. Not only are monosubstituted alkenes, aromatic
      aldehydes, and tert-alkyl aldehydes effective substrates, but monosubstituted
      olefins also react faster than those that are more substituted, and large or
      electron-rich aldehydes are more effective than small or electron-poor ones.
      Conceptually, in the presence of a nickel-phosphine catalyst, the combination of
      off-the-shelf alkenes, silyl triflates, and triethylamine functions as a
      replacement for an allylmetal reagent.

PMID- 16620108
TI  - Role of interstitial voids in oxides on formation and stabilization of reactive
      radicals: interstitial HO2 radicals in F2-laser-irradiated amorphous SiO2.
AB  - A procedure to produce stable hydroperoxy radicals (HO*2) in bulk amorphous
      SiO(2) (a-SiO(2)) has been developed. Oxygen molecules incorporated in the
      interstitial voids in a-SiO(2) react with mobile hydrogen atoms (H(0)) generated
      by the photolysis of silanol (SiOH) groups with F(2)-laser light (lambda = 157
      nm, hnu = 7.9 eV), resulting in the efficient creation of interstitial HO*2. The
      high yield of HO*2 suggests that the collisions of the reaction intermediate with
      the void wall play an important role in dissipating the excess energy of the
      intermediate instead of the triple collision observed in the gas phase reaction.
      The resultant HO*2 is thermally stable up to 100 degrees C.

PMID- 16620109
TI  - Molecular organization of cholesterol in unsaturated phosphatidylethanolamines: X
      ray diffraction and solid state 2H NMR reveal differences with
      phosphatidylcholines.
AB  - The major mammalian plasma membrane lipids are phosphatidylcholines (PCs),
      phosphatidylethanolamines (PEs), and cholesterol. Whereas PC-cholesterol
      interactions are well studied, far less is known about those between PE and
      cholesterol. Here, we investigated the molecular organization of cholesterol in
      PEs that vary in their degree of acyl chain unsaturation. For heteroacid sn-1
      saturated (palmitoyl), sn-2 unsaturated (various acyl chain) PEs, cholesterol
      solubility determined by X-ray diffraction was essentially identical with 1
      (oleoyl, 51 +/- 3 mol %) and 2 (linoleoyl, 49 +/- 2 mol %) double bonds before
      decreasing progressively with 4 (arachidonyl, 41 +/- 3 mol %) and 6
      (docosahexaenoyl, 31 +/- 3 mol %) double bonds. With 6 double bonds in each
      chain, cholesterol solubility was further reduced to 8.5 +/- 1 mol %. However,
      (2)H NMR experiments established that the orientation of cholesterol in the same
      heteroacid PE membranes was unaffected by the degree of acyl chain unsaturation.
      A tilt angle of 15 +/- 1 degrees was measured when equimolar [3alpha
      (2)H(1)]cholesterol was added, regardless of the number of double bonds in the sn
      2 chain. The finding that solubility of cholesterol in sn-1 saturated PEs depends
      on the amount of polyunsaturation in the sn-2 chain of PE differs from the
      equivalent PCs that universally incorporate approximately 50 mol % sterol. Unlike
      PCs, a differential in affinity for cholesterol and tendency to drive lateral
      segregation is inferred between polyunsaturated PEs. This distinction may have
      biological implications reflected by the health benefits of dietary
      polyunsaturated fatty acids that are often taken up into PE > PC.

PMID- 16620110
TI  - Prediction of microclimate pH in poly(lactic-co-glycolic acid) films.
AB  - An equilibrium mathematical model that accurately predicts microclimate pH (mupH)
      in thin biodegradable polymer films of poly(lactic-co-glycolic acid) (PLGA) is
      described. mupH kinetics was shown to be primarily a function of: (i) kinetics of
      water-soluble acid content and composition in the polymer matrix and (ii)
      polymer/water partition coefficient of water-soluble degradation products (P(i)).
      Polymers were coated on standard pH glass electrodes, and mupH was measured
      potentiometrically. Water-soluble acid distribution and content in PLGA films
      were determined by pre-derivatization HPLC. Polymer degradation products
      partitioned favorably in the polymer phase relative to water (P(i) range:
      approximately 6-100), and P(i) increased with increasing hydrophobicity of the
      acidic species according to a linear free energy law related to reversed phase
      HPLC retention time for the corresponding derivatized bromophenacyl esters. The
      mupH predicted by the model was in excellent agreement with experimental mupH for
      several PLGAs as a function of time and PLGA lactic/glycolic acid ratio. These
      data may be useful to slowly release pH-sensitive PLGA-encapsulated bioactive
      substances and provide a general framework for predicting partitioning behavior
      of degradation products in biodegradable polymers.

PMID- 16620111
TI  - Synthesis of a 10,000-membered library of molecules resembling carpanone and
      discovery of vesicular traffic inhibitors.
AB  - Split-and-pool synthesis of a 10,000-membered library of molecules resembling the
      natural product carpanone has been achieved. The synthesis features development
      of solid-phase multicomponent reactions between nitrogen nucleophiles, enones,
      and hydroxylamines, and a solid-phase application of the Huisgen cycloaddition
      affording substituted triazoles. The synthesis was performed in high-capacity
      (500 microm) polystyrene beads using a one bead-one stock solution strategy that
      enabled phenotypic screens of the resulting library. Using whole-cell
      fluorescence imaging, we discovered a series of molecules from the carpanone
      based library that inhibit exocytosis from the Golgi apparatus. The most potent
      member of this series has an IC(50) of 14 microM. We also report structure
      activity relationships for the molecules exhibiting this interesting phenotype.
      These inhibitors of exocytosis may be useful reagents for the study of vesicular
      traffic.

PMID- 16620113
TI  - Characterization of weak NH-pi intermolecular interactions of ammonia with
      various substituted pi-systems.
AB  - Among the several weak intermolecular interactions pervading chemistry and
      biology, the NH-pi interaction is one of the most widely known. Nevertheless its
      weak nature makes it one of the most poorly understood and characterized
      interactions. The present study details the results obtained on gas-phase
      complexes of ammonia with various substituted pi systems using both laser
      vibrational spectroscopy and ab initio calculations. The spectroscopic
      measurements carried out by applying one-color resonant two-photon ionization
      (R2PI) and IR-vibrational predissociation spectroscopy in the region of the NH
      stretches yield the first experimental NH stretching shifts of ammonia upon its
      interaction with various kinds of pi-systems. The experiments were complemented
      by ab initio calculations and energy decompositions, carried out at the second
      order Moller-Plesset (MP2) level of theory. The observed complexes show
      characteristic vibrational spectra which are very similar to the calculated ones,
      thereby allowing an in-depth analysis of the interaction forces and energies. The
      interaction energy of the conformers responsible for the observed vibrational
      spectra has the maximum contribution from dispersion energies. This implies that
      polarizabilities of the pi-electron systems play a very important role in
      governing the nature and geometry of the NH-pi interaction. The larger
      polarizability of ammonia as compared to water and the tendency to maximize the
      dispersion energy implies that the characteristics of the NH-pi interactions are
      markedly different from that of the corresponding OH-pi interactions.

PMID- 16620112
TI  - Deconvoluting the structural and drug-recognition complexity of the G-quadruplex
      forming region upstream of the bcl-2 P1 promoter.
AB  - The human bcl-2 gene contains a GC-rich region upstream of the P1 promoter that
      has been shown to be critically involved in the regulation of bcl-2 gene
      expression. We have demonstrated that the guanine-rich strand of the DNA in this
      region can form any one of three distinct intramolecular G-quadruplex structures.
      Mutation and deletion analysis permitted isolation and identification of three
      overlapping DNA sequences within this element that formed the three individual G
      quadruplexes. Each of these was characterized using nondenaturing gel analysis,
      DMS footprinting, and circular dichroism. The central G-quadruplex, which is the
      most stable, forms a mixed parallel/antiparallel structure consisting of three
      tetrads connected by loops of one, seven, and three bases. Three different G
      quadruplex-interactive agents were found to further stabilize these structures,
      with individual selectivity toward one or more of these G-quadruplexes.
      Collectively, these results suggest that the multiple G-quadruplexes identified
      in the promoter region of the bcl-2 gene are likely to play a similar role to the
      G-quadruplexes in the c-myc promoter in that their formation could serve to
      modulate gene transcription. Last, we demonstrate that the complexity of the G
      quadruplexes in the bcl-2 promoter extends beyond the ability to form any one of
      three separate G-quadruplexes to each having the capacity to form either three or
      six different loop isomers. These results are discussed in relation to the
      biological significance of this G-quadruplex-forming element in modulation of bcl
      2 gene expression and the inherent complexity of the system where different G
      quadruplexes and loop isomers are possible.

PMID- 16620114
TI  - Modeling of ligation-induced helix/loop displacements in myoglobin: toward an
      understanding of hemoglobin allostery.
AB  - Combining quantum and molecular mechanics (QM/MM) methods and protein structure
      prediction algorithms, helix and loop movements are computed along the pathway of
      CO dissociation from myoglobin (Mb). The results are compared with high
      resolution crystallographic data using sequence-displacement graphs. These graphs
      provide an unbiased method for evaluating main-chain segmental motions; they
      resolve an apparent disagreement between two sets of high-resolution crystal
      structures for MbCO and deoxyMb. The QM/MM modeling of the CO deligation
      reproduces the experimentally observed spin states and photodissociated crystal
      structure. The principal effect of CO dissociation is shown to be a concerted
      rotation of the E and F helices, which hold the heme like a clamshell. The
      rotation is a response to deligation forces, which impel the F helix away from
      the heme because of the Fe spin conversion, and which allow the E helix to
      collapse toward the heme as nonbonded contacts on the distal side are relieved.
      Additional helix and loop displacements stem from these primary events. In
      particular, the CD loop is found to be repositioned as a result of steric
      interactions with the water molecule that becomes H-bonded to the distal
      histidine in deoxyMb. A similar EF rotation and CD loop displacement are proposed
      to be the first steps along the allosteric pathway from the R to the T state in
      hemoglobin.

PMID- 16620115
TI  - In silico discovery of beta-secretase inhibitors.
AB  - Alzheimer's disease, the most common amyloid-associated disorder, accounts for
      the majority of the dementia diagnosed after the age of 60. The cleavage of the
      beta-amyloid precursor protein is initiated by beta-secretase (BACE-1), a
      membrane-bound aspartic protease, which has emerged as an important but difficult
      protein target. Here, an in silico screening approach consisting of fragment
      based docking, ligand conformational search by a genetic algorithm, and
      evaluation of free energy of binding was used to identify low-molecular-weight
      inhibitors of BACE-1. More than 300,000 small molecules were docked and about
      15,000 prioritized according to a linear interaction energy model with evaluation
      of solvation by continuum electrostatics. Eighty-eight compounds were tested in
      vitro, and 10 of them showed an IC(50) value lower than 100 microM in a BACE-1
      enzymatic assay. Interestingly, the 10 active compounds shared a triazine
      scaffold. Moreover, four of them were active in an assay with mammalian cells
      (EC(50) < 20 microM), indicating that they are cell-permeable. Therefore, these
      triazine derivatives are very promising lead candidates for BACE-1 inhibition.
      The discoveries of this series and two other series of nonpeptidic BACE-1
      inhibitors demonstrate the usefulness of our in silico high-throughput screening
      approach.

PMID- 16620116
TI  - The redox chemistry of the covalently immobilized native and low-pH forms of
      yeast iso-1-cytochrome c.
AB  - Cyclic voltammetry experiments were carried out on native Saccharomyces
      cerevisiae iso-1-cytochrome c and its C102T/N62C variant immobilized on bare
      polycrystalline gold electrode through the S-Au bond formed by a surface
      cysteine. Experiments were carried out at different temperatures (5-65 degrees C)
      and pH values (1.5-7). The E degrees ' value at pH 7 (+370 mV vs SHE) is
      approximately 100 mV higher than that for the protein in solution. This
      difference is enthalpic in origin and is proposed to be the result of the
      electrostatic repulsion among the densely packed molecules onto the electrode
      surface. Two additional electrochemical waves are observed upon lowering the pH
      below 5 (E degrees ' = +182 mV) and 3 (E degrees ' = +71 mV), which are
      attributed to two conformers (referred to as "intermediate" and "acidic",
      respectively) featuring an altered heme axial ligation. This is the first
      determination of the reduction potential for low-pH conformers of cytochrome c in
      the absence of denaturants. Since the native form of cytochrome c can be
      restored, bringing back the pH to neutrality, the possibility offered by this
      transition to reversibly modulate the redox potential of cytochrome c is
      appealing for bioelectronic applications. The immobilized C102T/N62C variant,
      which differs from the native protein in the orientation of the heme group with
      respect to the electrode, shows very similar reduction thermodynamics. For both
      species, the rate constant for electron transfer between the heme and the
      electrode increases for the acidic conformer, which is also found to act as a
      biocatalytic interface for dioxygen reduction.

PMID- 16620117
TI  - Oxidative addition of dihydrogen to (eta6-arene)Mo(PMe3)3 complexes: origin of
      the naphthalene and anthracene effects.
AB  - In contrast to the benzene and naphthalene compounds (eta(6)-PhH)Mo(PMe(3))(3)
      and (eta(6)-NpH)Mo(PMe(3))(3), the anthracene complex (eta(6)-AnH)Mo(PMe(3))(3)
      reacts with H(2) to undergo a haptotropic shift and give the eta(4)-anthracene
      compound (eta(4)-AnH)Mo(PMe(3))(3)H(2). Density functional theory calculations
      indicate that the increased facility of naphthalene and anthracene to adopt
      eta(4)-coordination modes compared to that of benzene is a consequence of the
      fact that the Mo-(eta(4)-ArH) bonding interaction increases in the sequence
      benzene < naphthalene < anthracene, while the Mo-(eta(6)-ArH) bonding interaction
      follows the sequence benzene > naphthalene approximately anthracene.

PMID- 16620118
TI  - Fluorescent lifetime quenching near d = 1.5 nm gold nanoparticles: probing NSET
      validity.
AB  - The fluorescence behavior of molecular dyes at discrete distances from 1.5 nm
      diameter gold nanoparticles as a function of distance and energy is investigated.
      Photoluminescence and luminescence lifetime measurements both demonstrate
      quenching behavior consistent with 1/d(4) separation distance from dye to the
      surface of the nanoparticle. In agreement with the model of Persson and Lang, all
      experimental data show that energy transfer to the metal surface is the dominant
      quenching mechanism, and the radiative rate is unchanged throughout the
      experiment.

PMID- 16620119
TI  - Ordered mesoporous Fe2O3 with crystalline walls.
AB  - Alpha-Fe(2)O(3) has been synthesized with an ordered mesoporous structure and
      crystalline walls that exhibit a near-single crystal-like order. The unique
      magnetic behavior of the material, distinct from bulk nanoparticles of alpha
      Fe(2)O(3) or mesoporous Fe(2)O(3) with disordered walls, has been established.
      Magnetic susceptibility, Mossbauer, and neutron diffraction data show that the
      material possesses the same long-range magnetic order as bulk alpha-Fe(2)O(3),
      despite the wall thickness being less than the 8 nm limit below which magnetic
      ordering breaks down in nanoparticulate alpha-Fe(2)O(3), yet the Morin transition
      of bulk alpha-Fe(2)O(3) is absent. It is also shown by TEM, PXRD, and EXAFS that
      alpha-Fe(2)O(3) with the same ordered mesoporous structure but disordered walls
      contains small crystalline domains. Mossbauer and magnetic susceptibility data
      demonstrate that this material exhibits no long-range magnetic order but
      superparamagnetic behavior.

PMID- 16620120
TI  - One-pot organocatalytic domino Michael-aldol and intramolecular SN2 reactions.
      Asymmetric synthesis of highly functionalized epoxycyclohexanone derivatives.
AB  - The development of the organocatalytic asymmetric one-pot Michael-Darzens
      condensation giving highly functionalized complex epoxycyclohexanone derivatives
      with up to four chiral centers is presented. Depending on the reaction
      conditions, either the polysubstituted 7-oxa-bicyclo[4.1.0]heptan-2-one ring
      system or 2-chloro-cyclohex-2-enone derivatives can be formed. For the former
      class of compounds a high diversity in substitution pattern is demonstrated, and
      the optically active products are obtained in excellent diastereo- and
      enantioselectivities. The potential synthetic applications of the products have
      been demonstrated by performing a series of highly diastereoselective
      transformations leading to optically active products useful for the life-science
      industry. Furthermore, mechanistic investigations on the formation of the chiral
      centers in the optically active epoxycyclohexanone are presented.

PMID- 16620121
TI  - Topology variation and loop structural homology in crystal and simulated
      structures of a bimolecular DNA quadruplex.
AB  - The topology of DNA quadruplexes depends on the nature and number of the
      nucleotides linking G-quartet motifs. To assess the effects of a three-nucleotide
      TTT linker, the crystal structure of the DNA sequence d(G(4)T(3)G(4)) has been
      determined at 1.5 A resolution, together with that of the brominated analogue
      d(G(4)(Br)UTTG(4)) at 2.4 A resolution. Both sequences form bimolecular
      intermolecular G-quadruplexes with lateral loops. d(G(4)(Br)UTTG(4)) crystallized
      in the monoclinic space group P2(1) with three quadruplex molecules in the
      asymmetric unit, two associating together as a head-to-head stacked dimer, and
      the third as a single head-to-tail dimer. The head-to-head dimers have two
      lateral loops on the same G-quadruplex face and form an eight-G-quartet stack,
      with a linear array of seven K(+) ions between the quartets. d(G(4)T(3)G(4))
      crystallized in the orthorhombic space group C222 and has a structure very
      similar to the head-to-tail dimer in the P2(1) unit cell. The sequence studied
      here is able to form several different folds; however, all four quadruplexes in
      the two structures have lateral loops, in contrast to the diagonal loops reported
      for the analogous quadruplex with T(4) loops. A total of seven independent T(3)
      loops were observed in the two structures. These can be classified into two
      discrete conformational classes, suggesting that these represent preferred loop
      conformations that are independent of crystal-packing forces.

PMID- 16620122
TI  - Nanostructured oligo(p-phenylene vinylene)/silicate hybrid films: one-step
      fabrication and energy transfer studies.
AB  - Novel hybrid materials containing silicate and charged oligo(p-phenylene
      vinylene) (OPV) amphiphiles were fabricated in one step by spin casting using
      evaporation-induced self assembly. The conjugated segments were substituted with
      trimethylammonium bromide groups at both termini, and tetraethyl orthosilicate
      served as the silicate precursor. X-ray diffraction scans of the hybrid films
      revealed Bragg diffraction peaks with d-spacings of 2.76 and 1.37 nm, indicating
      the presence of order in the hybrid structure. Optical properties of the hybrid
      films were characterized by UV-vis absorption and fluorescence spectra, and
      molecular orientation was characterized by IR spectroscopy. A rhodamine B
      derivative containing a triethoxysilane group was covalently incorporated into
      the silicate network of the films during the sol-gel reaction. Relative to
      disordered polymer films with identical organic composition, the ordered hybrid
      films revealed significantly enhanced emission from rhodamine B and also
      fluorescence quenching from OPV segments. These results indicate that the ordered
      and nanostructured environment leads to highly efficient energy transfer among
      organic components in these hybrid films.

PMID- 16620123
TI  - Two-site ionic labeling with pyranine: implications for structural dynamics
      studies of polymers and polypeptides by time-resolved fluorescence anisotropy.
AB  - Time-resolved fluorescence anisotropy (TRFA) is widely used to study dynamic
      motions of biomolecules in a variety of environments. However, depolarization due
      to rapid side chain motions often complicates the interpretation of anisotropy
      decay data and interferes with the accurate observation of segmental motions.
      Here, we demonstrate a new method for two-point ionic labeling of polymers and
      biomolecules that have appropriately spaced amino groups using the fluorescent
      probe 8-hydroxyl-1,3,6-trisulfonated pyrene (pyranine). TRFA analysis shows that
      such labeling provides a more rigid attachment of the fluorophore to the
      macromolecule than the covalent or single-point ionic labeling of amino groups,
      leading to time-resolved anisotropy decays that better reflect the backbone
      motion of the labeled polymer segment. Optimal coupling of pyranine to
      biomolecule dynamics is shown to be obtained for appropriately spaced Arg groups,
      and in such cases the ionic binding is stable up to 150 mM ionic strength. TRFA
      was used to monitor the behavior of pyranine-labeled poly(allylamine) (PAM) and
      poly-d-lysine (PL) in sodium silicate derived sol-gel materials and revealed
      significant restriction of backbone motion upon entrapment for both polymers, an
      observation that was not readily apparent in a previous study with entrapped
      fluorescein-labeled PAM and PL. The implications of these findings for
      fluorescence studies of polymer and biomolecule dynamics are discussed.

PMID- 16620124
TI  - Resonant electron capture by some amino acids and their methyl esters.
AB  - Resonant electron capture mass spectra of aliphatic and aromatic amino acids and
      their methyl esters show intense [M-H](-) negative ions in the low-energy range.
      Ion formation results from a predissociation mechanism mediated by the low-energy
      pi*oo resonant state. Methylation in general has little influence on the
      electronic structure according to quantum chemical calculations, but the
      corresponding ions from the methyl esters, [M-Me](-), could be ascertained to
      arise only at higher resonance energies. Aromatic amino acids are characterized
      by an additional low-energy fragmentation channel associated with the generation
      of negative ions with loss of the side chain. The complementary negative ions of
      the side chains are more efficiently produced at higher energies. The results
      have significant implications in biological systems as they suggest that amino
      acids can serve as radiation protectors since they have been found to efficiently
      thermalize electrons.

PMID- 16620125
TI  - Probing molecular structure at interfaces for comparison with bulk solution
      behavior: water/2-propanol mixtures monitored by vibrational sum frequency
      spectroscopy.
AB  - The orientation of the isopropyl group at the liquid/vapor interface in 2
      propanol/water binary mixtures was studied by vibrational sum frequency
      spectroscopy. The CH(3) stretch modes of the two methyl groups were used to
      determine the molecule's orientation by employing a novel united atom approach to
      model the (CH(3))(2)X moiety. For this purpose, the changes in the molecular
      susceptibility of the isopropyl group stretches were derived in the laboratory
      frame as a function of the tilt and twist angles. The results indicated that the
      methyl groups lay down on the surface at low alcohol mole fraction and gradually
      twisted with increasing mole fraction. At the azeotrope, x(iso) = 0.68, one of
      the methyl groups aligned approximately parallel to the surface normal, whereas
      the other was nearly parallel with the liquid/vapor interface. When the mole
      fraction of 2-propanol was higher than 0.68, the orientation of 2-propanol
      remained almost constant. The change in the alcohol's orientation with 2-propanol
      mole fraction closely tracked changes in its bulk activity coefficient. Such
      results lead to a picture in which the surface structure and bulk properties of
      the system are closely linked.

PMID- 16620126
TI  - Shape/size-controlled syntheses of metal nanoparticles for site-selective
      modification of carbon nanotubes.
AB  - Shape- and size-controlled syntheses of metal nanoparticles have been achieved by
      galvanic displacement reaction between an aqueous solution of metal salt and Cu
      foil substrate. In particular, cubic and spheric nanoparticles of Pt (Au) with a
      fairly narrow size distribution were produced by reacting K(2)PtCl(4) (HAuCl(4))
      with a Cu foil in an aqueous medium with and without CuCl(2) under different
      reaction conditions (e.g., different concentrations and reaction times). In
      conjunction with the substrate-enhanced electroless deposition (SEED) technique
      (Qu, L.; Dai, L. J. Am. Chem. Soc. 2005, 127, 10806), the shape/size-controlled
      syntheses have been successfully exploited to site-selectively deposit these
      metal nanoparticles onto the outerwall, innerwall, or end-tip of carbon nanotubes
      (CNTs). Asymmetric sidewall modification by attaching the innerwall and outerwall
      of CNTs with metal nanoparticles of different shapes was also achieved.
      Furthermore, it was demonstrated that the nanotube-supported Pt nanoparticles
      could be converted into hollow Au nanoboxes by galvanic displacement of Pt with
      Au. These CNT-supported metal nanoparticles were shown to possess interesting
      optical and electrocatalytic properties.

PMID- 16620127
TI  - Vibrational circular dichroism study of optically pure cryptophane-A.
AB  - Vibrational circular dichroism (VCD) measurements and density functional theory
      (DFT) calculations were used to obtain the absolute configuration of optically
      pure cryptophane-A molecule. This large molecule (120 atoms) that possess a
      globular shape, but no chiral centers, exceeds the molecular size of published
      structures for which VCD has been used to determine the absolute configuration.
      VCD spectra recorded in CDCl(3) solution for the two resolved enantiomers are
      near mirror images, and very good agreement between the observed IR and VCD
      spectra and intensity calculations performed at the DFT (B3PW91/6-31G) level
      establish, besides the absolute configuration, the preferential anti conformation
      of the aliphatic linkers of the chloroform-cryptophane-A complex. Experiments
      performed in CD(2)Cl(2) and C(2)D(2)Cl(4) solutions show no significant
      modifications in the IR and VCD spectra, indicating that the conformation of the
      aliphatic linkers is similar for empty (C(2)D(2)Cl(4) solution) and encaged
      (CDCl(3) and CD(2)Cl(2) solutions) cryptophane-A molecules.

PMID- 16620128
TI  - Alternating diacetylene copolymer utilizing perfluorophenyl-phenyl interactions.
AB  - The symmetric diacetylenes, 2,4-hexadiynylene dibenzoate 4 and 2,4-hexadiynylene
      bis(pentafluorobenzoate) 5, as well as the unsymmetric 6
      (pentafluorobenzoyloxy)hexa-2,4-diynyl benzoate 6 were prepared and investigated
      with respect to their reactivity toward topochemical polymerization in the
      crystalline state. The 1:1 cocrystal 4.5 was successfully polymerized to the
      corresponding poly(diacetylene) copolymer 7, as evidenced by solid-state (13)C
      NMR and Raman spectroscopy, as well as single-crystal structure analysis of the
      monomer-polymer cocrystal. Thus, perfluorophenyl-phenyl interactions were
      utilized as complementary supramolecular synthons in the cocrystallization of two
      different diacetylene monomers and their unprecedented conversion into a strictly
      alternating diacetylene copolymer.

PMID- 16620129
TI  - What is syncrystallization? States of the pH indicator methyl red in crystals of
      phthalic acid.
AB  - The concept of syncrystallization was reinvestigated by focusing on phthalic acid
      (PA) grown with methyl red (MR). Crystals are alternately red and yellow in
      adjacent growth sectors. X-ray structures of MR and its cocrystals, revealing MR
      in the neutral, zwitterionic, and protonated states, as well as measurements of
      linear birefringence and linear dichroism of mixed crystals, were used to
      investigate mechanisms of PA coloring. These experiments were complemented by
      force field calculations of the lowest energy stable surfaces of expressed facets
      and energies of MR on and in crystals, as well as molecular orbital calculations
      of MR. Two MR species were detected in PA having distinct energies,
      polarizations, and face selectivities. Assignments of structures to these MRs,
      previously thought to be neutral and protonated, required a nuanced analysis of
      hydrogen bonds. The essential difference between yellow and red species is
      whether the MR carboxylic acid proton is inter- or intramolecularly hydrogen
      bound. Inferences about mixed crystal structure drawn from an examination of
      cocrystals of PA and MR are inconsistent with polarization spectroscopy signaling
      caution when using stoichiometric compounds as models of dilute solid solutions.
      Upon heating mixed crystals, linear dichroism diminishes and oriented, elongated
      pools of MR separate and pass through the bulk in directions perpendicular to the
      direction of elongation. These batonnets subsequently crystallize leaving
      macroscopic oriented crystals of a MR-rich phase within PA. No evidence was found
      for the simultaneous crystallization of MR and PA; however, the MR reorientation
      on heating as well as the separation and recrystallization of a MR-rich phase are
      distinct processes that could be embraced by the literal meaning of
      syncrystallization.

PMID- 16620130
TI  - DABCO-Induced self-assembly of a trisporphyrin double-decker cage: thermodynamic
      characterization and guest recognition.
AB  - This paper describes the thermodynamic characterization of the self-assembly of a
      Zn trisporphyrin induced by coordination with 1,4-diazabicyclo[2.2.2]octane
      (DABCO) to form a stable 2:3 double-decker molecular coordination cage that
      recognizes benzene-1,3,5-tricarboxamides. The self-assembly process has been
      studied using UV-vis and (1)H NMR spectroscopy and quantitatively characterized
      in terms of a single stability constant that describes the strength of the
      individual coordination interactions and two effective molarities (EM) that
      describe the additional stability imparted by intramolecular cyclization. The EM
      values of the two consecutive cyclic intramolecular interactions are very
      similar. At micromolar concentrations, the formation of the fully assembled
      coordination cage is highly favored over the formation of intermediate species
      stabilized by fewer interactions, and so self-assembly is an all-or-nothing
      process. In contrast, at millimolar concentrations, the relative stability of
      intermediate species increases, leading to a stepwise self-assembly process, and
      a 2:2 intermediate can be clearly identified using (1)H NMR spectroscopy. The
      molecular recognition of benzene-1,3,5-tricarboxamides by the cage was
      investigated using (1)H NMR spectroscopy. The tricarboxamides bind inside the
      central cavity of the cage complex, and isothermal titration calorimetry (ITC)
      allowed the quantification of the stoichiometry and binding affinities.

PMID- 16620131
TI  - One-dimensional ion-conductive polymer films: alignment and fixation of ionic
      channels formed by self-organization of polymerizable columnar liquid crystals.
AB  - We have prepared two types of one-dimensional ion-conductive polymer films
      containing ion nanochannels that are both perpendicular and parallel to the film
      surface. These films have been obtained by photopolymerization of aligned
      columnar liquid crystals of a fan-shaped imidazolium salt having acrylate groups
      at the periphery. In the columnar structure, the ionic part self-assembles into
      the inner part of the column. The column is oriented macroscopically in two
      directions by different methods: orientation perpendicular to the modified
      surfaces of glass and indium tin oxide with 3-(aminopropyl)triethoxysilane and
      orientation parallel to a glass surface by mechanical shearing. Ionic
      conductivities have been measured for the films with columnar orientation
      vertical and parallel to the surface. Anisotropic ionic conductivities are
      observed for the oriented films fixed by photopolymerization. The ionic
      conductivities parallel to the columnar axis are higher than those perpendicular
      to the columnar axis because the lipophilic part functions as an ion-insulating
      part. The film with the columns oriented vertically to the surface shows an
      anisotropy of ionic conductivities higher than that of the film with the columns
      aligned parallel to the surface.

PMID- 16620132
TI  - Inverse miniemulsion ATRP: a new method for synthesis and functionalization of
      well-defined water-soluble/cross-linked polymeric particles.
AB  - A new methodology for the synthesis and functionalization of nanometer-sized
      colloidal particles consisting of well-defined, water-soluble, functional
      polymers with narrow molecular weight distribution (M(w)/M(n) < 1.3) was
      developed, utilizing atom transfer radical polymerization (ATRP) of water-soluble
      monomers in an inverse miniemulsion. The optional introduction of a disulfide
      functionalized cross-linker allowed for the synthesis of cross-linked
      (bio)degradable nanogels. Dynamic light scattering (DLS) and atomic force
      microscopy (AFM) measurements indicated that these particles possessed excellent
      colloidal stability. ATRP in inverse miniemulsion led to materials with several
      desirable features. The colloidal particles preserved a high degree of halogen
      chain-end functionality, which enabled further functionalization. Cross-linked
      nanogels with a uniformly cross-linked network were prepared. They were degraded
      to individual polymeric chains with relatively narrow molecular weight
      distribution (M(w)/M(n) < 1.5) in a reducing environment. Higher colloidal
      stability, higher swelling ratios, and better controlled degradability indicated
      that the nanogels prepared by ATRP were superior to their corresponding
      counterparts prepared by conventional free radical polymerization (RP) in inverse
      miniemulsion.

PMID- 16620133
TI  - Targeting virulence for antibacterial chemotherapy: identifying and
      characterising virulence factors for lead discovery.
AB  - The antibacterial drug discovery industry is fast losing participants; at the
      same time it is facing the challenge of developing new antibiotics that are
      effective against frequently occurring and multiply resistant organisms. One
      intriguing approach is to target bacterial virulence, and the last decade or so
      has seen a focus on bacterial pathogenesis along with the development of reagents
      and strategies that could make this possible. Several processes utilised by a
      range of bacteria to cause infection may be conserved enough to make attractive
      targets; indeed it is known that mammalian cells can affect bacterial gene
      expression and vice versa. Interesting targets involving virulence include type
      III secretion systems, two-component signal transduction systems, quorum sensing,
      and biofilm formation. In order to better understand these systems and
      strategies, investigators have developed novel strategies of their own, involving
      negative selections, surrogate models of infection, and screens for gene
      induction and antigenicity. Inhibitors of such targets would be unlikely to
      adversely affect patients, be cross-resistant to existing therapies, or cause
      resistance themselves. It might be the case that virulence target-based therapies
      would not be powerful enough to clear an existing infection alone, but if they
      are instead considered as adjunct therapy to existing antibiotics, or
      potentiators of the host immune response, they may show efficacy in a non
      traditional way.

PMID- 16620134
TI  - The role of intracellular calcium signals in inflammatory responses of polarised
      cystic fibrosis human airway epithelia.
AB  - Hyperinflammatory host responses to bacterial infection have been postulated to
      be a key step in the pathogenesis of cystic fibrosis (CF) lung disease. Previous
      studies have indicated that the CF airway epithelium itself contributes to the
      hyperinflammation of CF airways via an excessive inflammatory response to
      bacterial infection. However, it has been controversial whether the
      hyperinflammation of CF epithelia results from mutations in the CF transmembrane
      conductance regulator (CFTR) and/or is a consequence of persistent airways
      infection. Recent studies have demonstrated that intracellular calcium (Ca2+i)
      signals consequent to activation of apical G protein-coupled receptors (GPCRs) by
      pro-inflammatory mediators are increased in CF airway epithelia. Because of the
      relationship between Ca2+i mobilisation and inflammatory responses, the mechanism
      for the increased Ca2+i signals in CF was investigated and found to result from
      endoplasmic reticulum (ER) Ca2+ store expansion. The ER Ca2+ store expansion
      imparts a hyperinflammatory phenotype to chronically infected airway epithelia as
      a result of the larger Ca2+i mobilisation coupled to an excessive inflammatory
      response following GPCR activation. The ER expansion is not dependent on ER
      retention of misfolded DeltaF508 CFTR, but reflects an epithelial response
      acquired following persistent luminal airway infection. With respect to the
      mechanism of ER expansion in CF, the current view is that chronic airway
      epithelial infection triggers an unfolded protein response as a result of the
      increased flux of newly synthesised inflammatory mediators and defensive factors
      into the ER compartment. This unfolded protein response is coupled to X-box
      binding protein 1 (XBP-1) mRNA splicing and transcription of genes associated
      with the expansion of the protein-folding capacity of the ER (e.g. increases in
      ER chaperones and ER membranes). These studies have revealed a novel adaptive
      response in chronically infected airway epithelia, where the increased protein
      secretory capacity serves to promote epithelial homeostasis by increasing both
      the secretory and the reparative capacity of the cell. In addition, the increased
      ER-derived Ca2+i signaling allows the epithelia to amplify its inflammatory
      responses to infectious agents and exogenous toxicants. This review is devoted to
      a discussion of these recent findings and their implication for Ca2+i-dependent
      hyperinflammatory responses in CF airways.

PMID- 16620135
TI  - A newly synthesised molybdenum/ascorbic acid complex alleviates some effects of
      cardiomyopathy in streptozocin-induced diabetic rats.
AB  - BACKGROUND: Exogenous insulin does not prevent cardiac failure in patients with
      type 1 diabetes mellitus and a cardioprotective insulin mimic is greatly needed.
      Certain transition metals are known to act as insulin mimics and may be cardio-
      protective. In this study, the ability of a newly synthesised molybdenum/ascorbic
      acid complex to strengthen cardiac function was investigated. METHODS AND DESIGN:
      Male CD rats were assigned to one of five groups: non-diabetic control, non
      diabetic control treated with molybdenum/ascorbic acid complex, diabetic treated
      with sodium ascorbate, diabetic treated with molybdenum/ascorbic acid complex and
      untreated diabetics. Type 1 diabetes was induced by streptozocin injection. Once
      diabetes was confirmed, treatment was initiated by adding either the
      molybdenum/ascorbic acid complex or sodium ascorbate to the drinking water and
      continued for 6 weeks. Following the treatment period, the animals were
      terminated, and their hearts were excised and mounted in a working heart
      perfusion apparatus. Blood samples were taken for plasma glucose and plasma lipid
      level determination. Cardiac function was evaluated using 1 hour of low-flow
      ischaemic stress followed by 30 minutes of reperfusion. RESULTS: Hearts from the
      animals treated with the molybdenum/ascorbic acid complex displayed the best
      aerobic performance of all the diabetic animals. Blood glucose levels and blood
      lipid levels were significantly lower in animals treated with the complex than in
      other diabetic animals. The group treated with the complex also had a lower
      drinking rate than the other diabetic groups. Furthermore, hearts from animals
      treated with the molybdenum/ascorbic acid complex showed a greater degree of
      recovery from low-flow ischaemia than any other group. CONCLUSIONS: The
      molybdenum/ascorbic acid complex showed some significant insulin-mimic and
      cardioprotective effects. Further development of this complex could provide a
      drug useful for alleviating some of the cardiovascular problems associated with
      diabetes mellitus.

PMID- 16620136
TI  - Effect of dexmedetomidine on haemodynamic responses to laryngoscopy and
      intubation : perioperative haemodynamics and anaesthetic requirements.
AB  - BACKGROUND: Dexmedetomidine reduces the dose requirements for opioids and
      anaesthetic agents. The purpose of this study was to evaluate the effect of a
      single pre-induction intravenous dose of dexmedetomidine 1 microg/kg on
      cardiovascular response resulting from laryngoscopy and endotracheal intubation,
      need for anaesthetic agent and perioperative haemodynamic stability. METHODS:
      Fifty patients scheduled for elective minor surgery were randomised into two
      groups (dexmedetomidine group and placebo group, n = 25 in each group). During
      and after drug administration, the Ramsey sedation scale was applied every 5
      minutes. Fentanyl 1 microg/kg was administered to all patients and thiopental was
      given until lash reflex disappeared. Anaesthesia continuation was maintained with
      50% : 50%, oxygen : nitrous oxide. Sevoflurane concentration was adjusted to
      maintain systolic blood pressure within 20% of preoperative values. After
      extubation, the Steward awakening score was applied at 5 and 10 minutes.
      Haemodynamic parameters and adverse effects were recorded every 10 minutes for 1
      hour after surgery. RESULTS: During intubation the need for thiopental and
      sevoflurane concentration were decreased by 39% and 92%, respectively, in the
      dexmedetomidine group compared with the placebo group. In all groups, blood
      pressure and heart rate increased after tracheal intubation; both were
      significantly lower in the dexmedetomidine group than in the placebo group (p <
      0.05). Fentanyl requirement during the operation was 74.20 +/- 10.53microg in the
      dexmedetomidine group and 84.00 +/- 27.04microg in the placebo group (p < 0.05).
      At 5 minutes, the Steward scores were >6 in 56% of the dexmedetomidine group and
      in 4% of the placebo group (p < 0.05). At 10 minutes, sedation scores were > or
      =4 in all patients in the dexmedetomidine group (p < 0.05). Arterial blood
      pressure and heart rate in the postoperative period were significantly lower in
      the dexmedetomidine group compared with the placebo group (p < 0.05). CONCLUSION:
      Preoperative administration of a single dose of dexmedetomidine resulted in
      progressive increases in sedation, blunted the haemodynamic responses during
      laryngoscopy, and reduced opioid and anaesthetic requirements. Furthermore,
      dexmedetomidine decreased blood pressure and heart rate as well as the recovery
      time after the operation.

PMID- 16620137
TI  - Tipranavir: PNU 140690, tipranivir.
AB  - Tipranavir [PNU 140690, tipranivir, Aptivus] is a second-generation HIV
      dihydropyrone (a sulphonamide derivative), nonpeptidic protease inhibitor (NPPI)
      discovered by Pharmacia & Upjohn (now Pfizer) in the US. The compound is in
      development with Boehringer Ingelheim. Tipranavir has potent in vitro activity
      against a variety of HIV-1 laboratory strains and clinical isolates, including
      those resistant to ritonavir, as well as HIV-2. Tipranavir has been shown to act
      synergistically with other antiretroviral agents. The limited bioavailability of
      the hard gel (and first available) formulation of tipranavir led to the
      development of a soft capsule formulation that has better oral bioavailability.
      Pharmacia Corporation (now Pfizer) considers that the resistance profile of
      tipranavir may be sufficiently unique for it to be effective against protease
      inhibitor resistant virus. On 16 April 2003, Pharmacia Corporation was acquired
      by, and merged into, Pfizer. In February 2000, Boehringer Ingelheim acquired
      exclusive worldwide rights to tipranavir. Tipranavir was launched in the US in
      mid-2005. In June 2005, the US FDA granted accelerated approval to tipranavir
      capsules for use in combination treatment, based on 24-week data from ongoing
      clinical trials. The approved dose is Aptivus 500 mg taken with ritonavir 200 mg,
      twice daily. Aptivus 250 mg soft gel capsules are expected to be available in the
      second half of 2005. A submission was made to the FDA in October 2004 seeking
      accelerated approval. In May 2005, the Antiviral Drugs Advisory Committee of the
      FDA recommended the approval of tipranavir. The positive recommendation is based
      on data from the RESIST-1 and RESIST-2 studies. Also in October 2004, Boehringer
      Ingelheim submitted a Marketing Authorisation Application (MAA) to the European
      Medicines Agency (EMEA) for tipranavir for the treatment of HIV-1 infection in
      combination with other antiretroviral agents in patients who are protease
      inhibitor experienced. In July 2005, the Committee for Medicinal Products for
      Human Use (CHMP) issued a positive opinion for tipranavir in the European Union.
      If approved, the drug will be marketed in Europe too under the name Aptivus.
      Marketing authorisation under exceptional circumstances (accelerated approval) is
      expected before the end of 2005.A phase III clinical programme (RESIST-
      Randomised Evaluation of Strategic Intervention in Multi-drug ReSistant Patients
      with Tipranavir) was launched by Boehringer Ingelheim in February 2003. The
      RESIST programme consists of two phase III pivotal trials (RESIST 1 and RESIST 2)
      and two companion trials (study 1182.51 and RESIST 3) available at some sites for
      even more advanced patients. The trials are designed to further study the
      efficacy and safety of tipranavir (500 mg) boosted with low-dose (200 mg)
      ritonavir, taken twice daily, versus a low-dose ritonavir boosted comparator
      protease inhibitor that is chosen by the patient's physician on the basis of the
      treatment history and baseline resistance testing. Each patient will also receive
      an individualised background regimen. Study participants will all be highly
      treatment-experienced HIV-positive adults. RESIST 1 study enrolled 620 patients
      in the US, Canada and Australia and RESIST 2 enrolled more than 863 patients in
      Europe and South America. These trials are now fully recruited. The clinical
      endpoint for RESIST 1 is at 24 weeks and for RESIST 2, the endpoints are at 16
      and 24 weeks. Interim data from RESIST 1 (1182.12) were presented at the 44th
      Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington,
      DC, USA, in October 2004. Results from this study show that tipranavir is a
      viable treatment option for patients who have failed other protease inhibitors.
      In June 2004, Boehringer Ingelheim announced the expansion of enrolment criteria
      in the international Compassionate Use Programme to allow broader access to
      tipranavir for HIV patients in need of new treatment options. All countries
      participating in the tipranavir phase III programme are eligible to take part in
      the Compassionate Use programme, which is enrolling patients over the age of 18
      years, who are triple-antiretroviral class-experienced with at least two PI-based
      regimens. In November 2004, Boehringer Ingelheim opened the tipranavir Expanded
      Access Program (EAP) in the US, following a review of the protocol by the FDA.
      The programme will provide access to tipranavir for HIV-infected patients (> or
      =18 years old) who are not enrolled in the ongoing tipranavir clinical studies
      and who are triple-antiretroviral class-experienced with at least two previous PI
      based regimens, and have documented PI-resistance and need tipranavir to
      construct a viable treatment regimen. Eligibility is not dependent upon viral
      load or CD4+ cell count. Tiparanvir is also being evaluated in phase II studies
      for use in paediatric and treatment-naive patient populations. Phase II trials
      completed in the US have established the clinical activity of tiprananvir in both
      antiretroviral-naive and -experienced patients with HIV infection. The studies
      have also shown that tipranavir can be combined with ritonavir for maximal
      clinical benefit. In its 2003 Annual Report, Boehringer Ingelheim stated that the
      process- and paediatric- formulation development of tipranavir had been
      completed.

PMID- 16620138
TI  - The use of hormonal growth factors in the treatment of patients with short-bowel
      syndrome.
AB  - To date, the hormonal factors used in the treatment of patients with short-bowel
      syndrome have been growth hormone and glucagon-like peptide (GLP)-2. In high-dose
      growth hormone studies, the effects on wet-weight absorption of approximately 0.7
      kg/day have mainly been described in short-bowel syndrome patients with a
      preserved colon who also received oral rehydration solutions. Treatment with high
      doses of growth hormone is associated with severe adverse effects in the majority
      of patients. Low-dose growth hormone increased energy absorption by approximately
      1.8 MJ/day in a group of 12 short-bowel syndrome patients (9 with a preserved
      colon), but it did not affect wet-weight absorption. Growth hormone does not seem
      to affect either wet-weight or energy absorption in patients with a jejunostomy.
      GLP-2 and the analogue teduglutide mainly affect wet-weight absorption, resulting
      in a mean increase in wet-weight absorption of 0.4-0.7 kg/day. The effects on
      energy absorption are minor at 0.4-0.8 MJ/day. However, these effects are seen in
      all short-bowel syndrome patients, regardless of anatomy, and the adverse effects
      are minor. In all studies employing growth hormone or GLP-2, the effects are
      transient, disappearing when treatments are discontinued. With the need for long
      term treatment, adverse effects and safety issues become important. Therefore, it
      is recommended that treatment is initiated in research settings only and that
      close monitoring of the long-term effects is a part of the protocol.

PMID- 16620139
TI  - Pharmacological management of women with mixed urinary incontinence.
AB  - Mixed urinary incontinence (MUI) is a symptomatic diagnosis. It is defined by the
      International Continence Society as the complaint of involuntary leakage
      associated with urgency and also with exertion, effort, sneezing and coughing. A
      search of medical databases revealed that only a small number of limited studies
      that assess the prevalence, epidemiology and treatment of MUI have been
      conducted. Most studies have looked separately at either stress urinary
      incontinence or urgency urinary incontinence. Thus, management of MUI involves a
      combination of treatments for both stress and urgency incontinence, but should
      concentrate initially on the most bothersome and/or predominant symptom. Initial
      management includes an accurate history and examination, which is supplemented by
      a bladder diary and quality-of-life questionnaire. Once a preliminary diagnosis
      is established, first-line therapy includes patient education and lifestyle
      interventions, such as weight loss. This is supplemented by pelvic floor muscle
      training and bladder training, which help with both components of MUI. Oral
      pharmacotherapy often acts synergistically with the previous treatments; however,
      only very few randomised, placebo-controlled trials have looked at the effects of
      pharmacotherapy on MUI. The two main classes of drugs are the antimuscarinics,
      which are effective in urgency incontinence, and the serotonin-norepinephrine re
      uptake inhibitors, which are effective in stress incontinence. Combination of
      these two drug classes is a feasible option but has not been tested in any trials
      to date. Should these treatments fail, then patients should be referred for
      cystometry to confirm the diagnosis. Treatment options available following
      urodynamics include invasive minor and major surgical procedures, which either
      treat the stress or urgency component of MUI but not both. Surgical procedures
      carry the risk of infection, haemorrhage and failure.

PMID- 16620140
TI  - Management of restless legs syndrome in patients on dialysis.
AB  - Restless legs syndrome (RLS) is characterised by an urge to move the legs,
      uncomfortable sensations in the legs and worsening of these symptoms during rest
      with at least temporary relief brought on by activity. RLS occurs in 3-15% of the
      general population and in 10-30% of patients on maintenance dialysis. RLS may
      lead to severe sleep onset or maintenance insomnia, and greatly impaired quality
      of life. Current recommendations suggest dopaminergic therapy (levodopa or
      dopamine receptor agonists: pramipexol, ropinirole, pergolide or cabergoline) as
      the first-line treatment for RLS. This group of medications is effective in
      reducing RLS symptoms in the general population; limited information is available
      on the effect of these drugs in patients with renal failure. However, it must be
      noted that most published studies in uraemic patients had short treatment periods
      and insufficient statistical power because of small sample size. Frequent adverse
      effects of levodopa, seen mainly with continuous use, may limit its use
      significantly. Rebound and augmentation, problems relatively frequently seen with
      levodopa, seem to be less prevalent with the use of dopamine receptor agonists,
      although properly designed comparative trials are still needed to address this
      question. Alternative treatment options for RLS are gabapentin, benzodiazepines
      and opioids. For all of these medications, there are only very limited data
      available on their effectiveness and safety profile in patients on maintenance
      dialysis. Referral to a specialist for RLS management should be considered for
      patients with refractory RLS.

PMID- 16620141
TI  - B cell-targeted therapy for rheumatoid arthritis: an update on the evidence.
AB  - Rheumatoid arthritis (RA) is a human systemic autoimmune disease with a
      prevalence of about 1%. Although an important role for B cells has been
      demonstrated in animal models of autoimmune, inflammatory arthritis, the
      importance of B cells in RA has been controversial for decades. The development
      of therapies targeting B cells may help to resolve this debate. Rituximab, a
      mouse-human chimeric monoclonal antibody against the B cell-specific antigen
      CD20, was the first B cell-targeted therapy tested in double-blind, placebo
      controlled trials for RA. On the basis of the data from three separate trials,
      addition of rituximab to methotrexate appears to reduce significantly the signs
      and symptoms of rheumatoid factor-seropositive RA, as assessed by American
      College of Rheumatology (ACR) 20, 50 and 70 response criteria, and to be
      relatively safe. Significant questions about rituximab therapy still need to be
      addressed, including whether or not treatment with rituximab reduces radiographic
      progression of joint damage, the safety and efficacy of repeated courses of
      rituximab, and the long-term effects of rituximab on the immune system.
      Preliminary data on treatment of RA with belimumab, a fully human monoclonal
      antibody against B lymphocyte stimulator (a growth and survival factor for B
      cells) is now available. In a double-blind, placebo-controlled, phase II trial,
      belimumab was well tolerated and had a significant beneficial effect on the ACR
      20 response. Thus, therapies specifically targeting B cells do appear to be
      effective in the treatment of RA, providing direct evidence that B cells are
      important in the pathogenesis of RA.

PMID- 16620143
TI  - Dexmethylphenidate extended release: in attention-deficit hyperactivity disorder.
AB  - Dexmethylphenidate extended release (XR) is an orally administered, bimodal
      release, capsule formulation of the active d-enantiomer of methylphenidate (MPH),
      which inhibits dopamine and norepinephrine (noradrenaline) reuptake to increase
      their concentration in the extraneuronal space. A single dose of
      dexmethylphenidate XR mimics the pharmacokinetic profile of two doses of
      dexmethylphenidate immediate-release formulation administered 4 hours apart,
      albeit with less fluctuation in plasma concentration. Once-daily
      dexmethylphenidate XR was more effective than placebo in reducing attention
      deficit hyperactivity disorder (ADHD) symptom scores in children, adolescents and
      adults with ADHD in four randomised, double-blind, placebo-controlled trials of
      up to 7 weeks' duration. In crossover trials in children (aged 6-12 years),
      dexmethylphenidate XR 20 mg/day reduced mean ADHD symptom scores 1 hour after
      administration (by 43% in one trial) and was significantly better than placebo
      for up to 12 hours. Dexmethylphenidate XR 5-30 mg/day reduced mean ADHD symptom
      scores by 49%, while scores declined by 16% with placebo in a 7-week trial in
      children and adolescents (aged 6-17 years). Dexmethylphenidate XR 20, 30 or 40
      mg/day reduced ADHD symptom scores by 36-46% versus a 21% reduction with placebo
      in a 5-week trial in adults (aged 18-60 years). Dexmethylphenidate XR was
      generally well tolerated in children, adolescents and adults with ADHD, with an
      adverse-event profile typical of MPH.

PMID- 16620142
TI  - Advances in the treatment of testicular cancer.
AB  - Testicular cancer is the most common solid tumour in young men, and the treatment
      of testicular germ cell tumours (TGCT) has been called a success story of medical
      oncology, germ cell cancer being regarded as the "model of a curable neoplasm".
      Even with metastatic disease, high cure rates can be achieved: the overall 5-year
      survival for all stages of TGCT is approximately 80%. Today, elaborate systems
      for prognostic evaluation for gonadal and extragonadal germ cell tumours
      facilitate the choice of the most appropriate therapy for individual patients. In
      doing so, the ultimate goal of treatment is tumour-free survival for any patient
      with TGCT. This goal has already been reached for >99% of the patients with early
      stage tumours, as well as for the majority of patients with advanced disease (56%
      of patients with metastases are considered to have a good prognosis at the time
      of diagnosis; the 5-year survival rate for this group is 90%). However, patients
      with 'intermediate' or 'poor' prognosis at the time of diagnosis, as well as
      patients with relapsed disease after cisplatin-containing therapy, still have an
      unsatisfactorily low 5-year survival rate after standard therapy with PEB
      (cisplatin, etoposide, bleomycin) of only 80%, 45-55% and 20-25%,
      respectively.Therefore, our goals must be (i) to limit acute and chronic toxicity
      by avoiding overtreatment for patients with localised disease and/or good
      prognosis with advanced disease; and (ii) to identify patients with poor
      prognosis and treat them in specialised centres, where not only is optimal
      interdisciplinary care available but new treatment strategies are being applied.
      For example, tandem high-dose chemotherapy regimens might be effective in
      achieving higher cure rates in these patients.

PMID- 16620146
TI  - Triflusal: a review of its use in cerebral infarction and myocardial infarction,
      and as thromboprophylaxis in atrial fibrillation.
AB  - Triflusal (Aflen, Disgren, Tecnosal, Triflux) is a novel platelet antiaggregant
      with structural similarities to salicylates, but which is not derived from
      aspirin. It has similar efficacy to aspirin in patients with cerebral or
      myocardial infarction, but has a reduced risk of haemorrhagic complications. In
      addition, triflusal plus moderate-intensity anticoagulation has demonstrated
      efficacy when used as thromboprophylaxis in atrial fibrillation. As such,
      triflusal has a role in the primary prevention of cerebrovascular events in
      atrial fibrillation, and for the secondary prevention of cerebral and myocardial
      infarction, primarily as an alternative to aspirin in patients for whom aspirin
      is unsuitable.

PMID- 16620147
TI  - Ranolazine: a review of its use in chronic stable angina pectoris.
AB  - Ranolazine (Ranexa), a piperazine derivative, is a new antianginal agent approved
      for the treatment of chronic stable angina pectoris for use as combination
      therapy when angina is not adequately controlled with other antianginal agents.
      While the exact mechanism of action of ranolazine is not known, its antianginal
      and anti-ischaemic effects do not appear to depend upon changes in blood pressure
      or heart rate. An extended-release (ER) oral formulation of ranolazine has been
      developed to facilitate twice-daily administration whilst maintaining
      therapeutically effective plasma concentrations. In patients with chronic stable
      angina, ranolazine ER monotherapy was shown to improve exercise duration at
      trough plasma drug concentration in a dose-dependent manner compared with
      placebo. The drug was effective as adjunctive therapy in patients with chronic
      stable angina whose condition was not controlled adequately with conventional
      antianginal therapy. In randomised clinical trials, ranolazine ER was well
      tolerated, with no overt effects on cardiovascular haemodynamics or conduction,
      apart from a modest increase in corrected QT (QTc) interval (but no torsades de
      pointes). Importantly, the efficacy and tolerability of ranolazine ER were not
      affected by comorbid conditions, including old age, heart failure (HF) or
      diabetes mellitus. Comparative trials of ranolazine ER with other antianginal
      agents and trials examining its effects on long-term morbidity and mortality in
      patients with ischaemic heart disease are required to determine with greater
      certainty the place of the drug in current antianginal therapy. Nevertheless,
      ranolazine ER may well prove to be a useful alternative and adjunct to
      conventional haemodynamic antianginal therapy in the treatment of chronic stable
      angina.

PMID- 16620148
TI  - Ibandronic acid: a review of its use in the treatment of bone metastases of
      breast cancer.
AB  - Ibandronic acid (Bondronat) is a potent, new-generation, nitrogen-containing
      bisphosphonate, available in both intravenous and oral formulations, which
      effectively inhibits osteoclast-mediated bone resorption. In clinical trials, the
      two formulations were equally effective in preventing skeletal-related events and
      improving quality of life in patients with bone metastases of breast cancer. Both
      intravenous and oral ibandronic acid reduced metastatic bone pain scores below
      baseline levels for up to 2 years. Oral ibandronic acid is administered as a
      single 50 mg tablet taken once daily. It suppressed bone resorption in breast
      cancer patients with bone metastases to an extent similar to that observed with
      intravenous zoledronic acid. Both intravenous and oral ibandronic acid were well
      tolerated with no evidence of renal toxicity. Ibandronic acid is therefore a
      valuable addition to the bisphosphonates used in the treatment of bone metastases
      of breast cancer, offering high potency and the convenience of oral
      administration, combined with the absence of renal toxicity.

PMID- 16620149
TI  - Myelopathy in Sjogren's syndrome: a causative role for cobalamin (vitamin B12)
      deficiency.

PMID- 16620150
TI  - Parallel evolution of the genetic code in arthropod mitochondrial genomes.
AB  - The genetic code provides the translation table necessary to transform the
      information contained in DNA into the language of proteins. In this table, a
      correspondence between each codon and each amino acid is established: tRNA is the
      main adaptor that links the two. Although the genetic code is nearly universal,
      several variants of this code have been described in a wide range of nuclear and
      organellar systems, especially in metazoan mitochondria. These variants are
      generally found by searching for conserved positions that consistently code for a
      specific alternative amino acid in a new species. We have devised an accurate
      computational method to automate these comparisons, and have tested it with 626
      metazoan mitochondrial genomes. Our results indicate that several arthropods have
      a new genetic code and translate the codon AGG as lysine instead of serine (as in
      the invertebrate mitochondrial genetic code) or arginine (as in the standard
      genetic code). We have investigated the evolution of the genetic code in the
      arthropods and found several events of parallel evolution in which the AGG codon
      was reassigned between serine and lysine. Our analyses also revealed correlated
      evolution between the arthropod genetic codes and the tRNA-Lys/-Ser, which show
      specific point mutations at the anticodons. These rather simple mutations,
      together with a low usage of the AGG codon, might explain the recurrence of the
      AGG reassignments.

PMID- 16620151
TI  - Molecular-level variation affects population growth in a butterfly
      metapopulation.
AB  - The dynamics of natural populations are thought to be dominated by demographic
      and environmental processes with little influence of intraspecific genetic
      variation and natural selection, apart from inbreeding depression possibly
      reducing population growth in small populations. Here we analyse hundreds of well
      characterised local populations in a large metapopulation of the Glanville
      fritillary butterfly (Melitaea cinxia), which persists in a balance between
      stochastic local extinctions and recolonisations in a network of 4,000 discrete
      habitat patches. We show that the allelic composition of the glycolytic enzyme
      phosphoglucose isomerase (Pgi) has a significant effect on the growth of local
      populations, consistent with previously reported effects of allelic variation on
      flight metabolic performance and fecundity in the Glanville fritillary and Colias
      butterflies. The strength and the sign of the molecular effect on population
      growth are sensitive to the ecological context (the area and spatial connectivity
      of the habitat patches), which affects genotype-specific gene flow and the
      influence of migration on the dynamics of local populations. The biological
      significance of the results for Pgi is underscored by lack of any association
      between population growth and allelic variation at six other loci typed in the
      same material. In demonstrating, to our knowledge for the first time, that
      molecular variation in a candidate gene affects population growth, this study
      challenges the perception that differential performance of individual genotypes,
      leading to differential fitness, is irrelevant to population dynamics. These
      results also demonstrate that the spatial configuration of habitat and spatial
      dynamics of populations contribute to maintenance of Pgi polymorphism in this
      species.

PMID- 16620152
TI  - Microstimulation of frontal cortex can reorder a remembered spatial sequence.
AB  - Complex goal-directed behaviors extend over time and thus depend on the ability
      to serially order memories and assemble compound, temporally coordinated
      movements. Theories of sequential processing range from simple associative
      chaining to hierarchical models in which order is encoded explicitly and
      separately from sequence components. To examine how short-term memory and
      planning for sequences might be coded, we used microstimulation to perturb neural
      activity in the supplementary eye field (SEF) while animals held a sequence of
      two cued locations in memory over a short delay. We found that stimulation
      affected the order in which animals saccaded to the locations, but not the memory
      for which locations were cued. These results imply that memory for sequential
      order can be dissociated from that of its components. Furthermore, stimulation of
      the SEF appeared to bias sequence endpoints to converge toward a location in
      contralateral space, suggesting that this area encodes sequences in terms of
      their endpoints rather than their individual components.

PMID- 16620153
TI  - Space asymmetry directs preferential sperm entry in the absence of polarity in
      the mouse oocyte.
AB  - Knowledge about the mechanism that establishes embryonic polarity is fundamental
      in understanding mammalian development. In re-addressing several controversial
      claims, we recently proposed a model in which mouse embryonic polarity is not
      specified until the blastocyst stage. Before fertilization, the fully
      differentiated oocyte has been characterized as "polarized," and we indeed
      observed that the sperm preferentially enters the polar body half. Here we show
      that preferential sperm entry is not due to an intrinsic polarity of the oocyte,
      since fertilization takes place uniformly when the zona pellucida is removed. We
      suggest that the term "asymmetry" denotes morphological differences, whereas
      "polarity" in addition implies developmental consequences. Thus, the mouse oocyte
      can be considered "asymmetric" but "non-polarized." The penetration through the
      zona pellucida is also random, and a significant proportion of sperm binds to the
      oocyte membrane at a point distant from the zona penetration site. Time-lapse
      recordings confirmed that sperm swim around the perivitelline space before
      fertilization. Experimental enlargement of the perivitelline space in the non
      polar body half increased the regional probability of fertilization. Based on
      these experiments, we propose a model in which the space asymmetry exerted by the
      first polar body and the zona pellucida directs sperm entry preferentially to the
      polar body half, with no need for oocyte polarity.

PMID- 16620154
TI  - UVB effects on the photosystem II-D1 protein of phytoplankton and natural
      phytoplankton communities.
AB  - The reaction center of photosystem II is susceptible to photodamage. In
      particular the D1 protein located in the photosystem II core has a rapid, light
      dependent turnover termed the photosystem II repair cycle that, under
      illumination, degrades and resynthesizes D1 protein to limit accumulation of
      photodamaged photosystem II. Most studies concerning the effects of UVB (280-320
      nm) on this cycle have been on cyanobacteria or specific phytoplankton species
      rather than on natural communities of phytoplankton. During a 5-year
      multidisciplinary project on the effects of UV radiation (200-400 nm) on natural
      systems, the effects of UVB on the D1 protein of natural phytoplankton
      communities were assessed. This review provides an overview of photoinhibitory
      effects of light on cultured and natural phytoplankton, with an emphasis on the
      interrelation of UVB exposure, D1 protein degradation and the repair of
      photosystem II through D1 resynthesis. Although the UVB component of the solar
      spectrum contributes to the primary photoinactivation of photosystem II, we
      conclude that, in natural communities, inhibition of the rate of the photosystem
      II repair cycle is a more important influence of UVB on primary productivity.
      Indeed, exposing tropical and temperate phytoplankton communities to supplemented
      UVB had more inhibitory effect on D1 synthesis than on the D1 degradation process
      itself. However, the rate of net D1 damage was faster for the tropical
      communities, likely because of the effects of high ambient light and water
      temperature on mechanisms of protein degradation and synthesis.

PMID- 16620157
TI  - Effects of UV radiation on usnic acid in Xanthoparmelia microspora (Mull. Arg.
      Hale).

PMID- 16620159
TI  - Telehomecare: where are we?

PMID- 16620158
TI  - Significance of CpG methylation for solar UV-induced mutagenesis and
      carcinogenesis in skin.
AB  - Mutations detected in the p53 gene in human nonmelanoma skin cancers show a
      highly UV-specific mutation pattern, a dominance of C --> T base substitutions at
      dipyrimidine sites plus frequent CC --> TT tandem substitutions, indicating a
      major involvement of solar UV in the skin carcinogenesis. These mutations also
      have another important characteristic of frequent occurrences at CpG dinucleotide
      sites, some of which actually show prominent hotspots in the p53 gene. Although
      mammalian solar UV-induced mutation spectra were studied intensively in the aprt
      gene using rodent cultured cells and the UV-specific mutation pattern was
      confirmed, the second characteristic of the p53 mutations in human skin cancers
      had not been reproduced. However, studies with transgenic mouse systems developed
      thereafter for mutation research, which harbor methyl CpG-abundant transgenes as
      mutation markers, yielded complete reproductions of the situation of the human
      skin cancer mutations in terms of both the UV-specific pattern and the frequent
      occurrence at CpG sites. In this review, we evaluate the significance of the CpG
      methylation for solar UV mutagenesis in the mammalian genome, which would lead to
      skin carcinogenesis. We propose that the UV-specific mutations at methylated CpG
      sites, C --> T transitions at methyl CpG-associated dipyrimidine sites, are a
      solar UV-specific mutation signature, and have estimated the wavelength range
      effective for the solar-UV-specific mutation as 310-340 nm. We also recommend the
      use of methyl CpG-enriched sequences as mutational targets for studies on solar
      UV genotoxicity for human, rather than conventional mammalian mutational marker
      genes such as the aprt and hprt genes.

PMID- 16620161
TI  - Telethinking: with Rhonda Chetney, R.N., M.S. Interview by Vicki Glaser.

PMID- 16620162
TI  - Results of implementation of the DigiScope for diabetic retinopathy assessment in
      the primary care environment.
AB  - Approximately 50% of patients with diabetes in the United States do not undergo
      recommended ocular evaluations for diabetic retinopathy. The DigiScope (EyeTel
      Imaging, Inc., Columbia, MD) was developed as a cost-effective and practical
      telemedicine digital imaging system to screen for diabetic retinopathy in the
      primary care physician's (PCP) office. The DigiScope has been validated against
      seven-field stereo color fundus photography for the detection of diabetic
      retinopathy. This study reports on the implementation of the DigiScope for
      diabetic retinopathy assessment in the primary care environment. In PCP's
      offices, patients with diabetes who had not undergone an eye examination in the
      past year were imaged with the DigiScope. The images were transmitted to a
      reading center where the need for referral to an ophthalmologist was determined.
      Nonurgent referral was recommended for patients with diabetic retinopathy greater
      than a few micro-aneurysms, other ocular pathology, or unreadable images.
      Referral was deemed "urgent" for patients with sight-threatening disease and
      evaluation by an ophthalmologist within 72 hours was recommended. Between October
      1, 2002 and March 31, 2771 patients with diabetes underwent DigiScope imaging at
      multiple sites. Nonurgent referral was recommended for 468 patients (17%). Urgent
      referral was recommended for 71 patients (3%). The images were unreadable in 295
      cases (11%). This study indicates that implementation of the DigiScope in the
      primary care setting is practical and allows screening of patients with diabetes
      who are otherwise not receiving recommended eye examinations.

PMID- 16620163
TI  - Making the business case for telemedicine: an interactive spreadsheet.
AB  - The objective of this study was to demonstrate the business case for telemedicine
      in nonrural areas. We developed an interactive spreadsheet to conduct multiple
      financial analyses under different capital investment, revenue, and expense
      scenarios. We applied the spreadsheet to the specific case of poststroke
      rehabilitation in urban settings. The setting involved outpatient clinics
      associated with a freestanding rehabilitation hospital in Oklahoma. Our baseline
      scenario used historical financial data from face-to-face encounters as the
      baseline for payer and volume mix. We assumed a cost of capital of 10% to finance
      the project. The outcome measures were financial breakeven points and internal
      rate of return. A total of 340 telemedicine visits will generate a positive net
      cash flow each year. The project is expected to recoup the initial investment by
      the fourth year, produce a positive present value dollar return of more than
      $2,000, and earn rate of return of 20%, which exceeds the hospital's cost of
      capital. The business case is demonstrated for this scenario. Urban telemedicine
      programs can be financially self-sustaining without accounting for reductions in
      travel time by providers or patients. Urban telemedicine programs can be a sound
      business investment and not depend on grants or subsidies for start-up funding.
      There are several key decision points that affect breakeven points and return on
      investment. The best business strategy is to approach the decision as whether or
      not to build a new clinic.

PMID- 16620164
TI  - Rural outreach in home telehealth: assessing challenges and reviewing successes.
AB  - Most home health agencies that adopt home telehealth tend to be located in urban
      or metropolitan areas. This paper discusses a 3-year pilot of home telehealth in
      four rural areas. Several challenges related to the rural nature of the home
      health agencies were recognized. These challenges are discussed with
      recommendations for assessing rural home health agencies for home telehealth. Our
      findings suggest ways to improve the implementation of home telehealth for rural
      home health agencies. In addition to the challenges, successes were realized as
      well. Approximately 145 travel hours and 7500 miles of nurse travel were avoided
      through the use of home telehealth during the program. Patient examples show
      improvements in their medical conditions, which the nursing staff thought would
      not have been accomplished without the more frequent monitoring that home
      telehealth allowed the agencies to provide.

PMID- 16620165
TI  - Cost-minimization analysis of a telehomecare program for patients with chronic
      obstructive pulmonary disease.
AB  - A cost-minimization analysis was performed on a telehomecare program for patients
      with a chronic obstructive pulmonary disease (COPD). The research was quasi
      experimental and included a control group. We compared the effects and costs of
      care provided to a group of 19 patients under a telehomecare program to a
      comparable group of 10 patients receiving regular home care without
      telemonitoring. Our results clearly indicate that there were fewer home visits by
      nurses and hospitalizations for patients in the experimental group. However,
      these patients made more telephone calls than patients in the control group,
      although this difference was not statistically significant. Of utmost importance,
      the cost-minimization analysis yielded positive results. Indeed, telemonitoring
      over a 6-month period generated $355 in savings per patient, or a net gain of 15%
      compared to traditional home care. Our study confirms the findings of previous
      studies that analyzed the efficacy of telemonitoring for patients with COPD.
      Patients were found to easily accept the idea of using the technology, and the
      telehomecare program demonstrated significant clinical benefits. Financial
      advantages of the program could have been more pronounced had it not been for the
      cost of technology that effectively erased a good portion of the savings.

PMID- 16620166
TI  - Is there a business case for telehealth in home health agencies?
AB  - Telehealth is a tool being considered by home health agencies (HHAs) to help
      manage costs. Most HHAs in the United States rely on Medicare reimbursement as
      their primary revenue source. With the implementation of a new payment system in
      October 2000, HHAs went from a cost-based, fee-for-service payment to a per
      episode prospective payment reimbursement model. For HHAs, the revenue goal
      changed from maximizing the number of visits under feefor- service to maximizing
      the number of patients and managing the episode within the prospective payment
      reimbursement formula. This paper addresses whether or not there is a financial
      business case for telehealth in HHAs. For this research effort, building a
      business case involved identifying and measuring the factors that contribute to
      the financial effectiveness of the home health organization. Utilizing a return
      on investment breakeven analysis model, we investigated the financial impact of
      telehealth, utilizing data from 32 HHAs in the Commonwealth of Pennsylvania. The
      breakeven analysis demonstrated that telehealth can have a positive impact on the
      HHA's financial position. Results indicate that HHAs should seriously consider
      the use of telehealth as part of their agency's care delivery model.

PMID- 16620167
TI  - Home telehealth improves clinical outcomes at lower cost for home healthcare.
AB  - Patient outcomes and cost were compared when home healthcare was delivered by
      telemedicine or by traditional means for patients receiving skilled nursing care
      at home. A randomized controlled trial was established using three groups. The
      first group, control group C, received traditional skilled nursing care at home.
      The second group, video intervention group V, received traditional skilled
      nursing care at home and virtual visits using videoconferencing technology. The
      third group, monitoring intervention group M, received traditional skilled
      nursing care at home, virtual visits using videoconferencing technology, and
      physiologic monitoring for their underlying chronic condition. Discharge to a
      higher level of care (hospital, nursing home) within 6 months of study
      participation was 42% for C subjects, 21% for V subjects, and 15% for M subjects.
      There was no difference in mortality between the groups. Morbidity, as evaluated
      by changes in the knowledge, behavior and status scales of the Omaha Assessment
      Tool, showed no differences between groups except for increased scores for
      activities of daily living at study discharge in the V and M groups. The average
      visit costs were $48.27 for face-to-face home visits, $22.11 for average virtual
      visits (video group), and $32.06 and $38.62 for average monitoring group visits
      for congestive heart failure and chronic obstructive pulmonary disease subjects,
      respectively. This study has demonstrated that virtual visits between a skilled
      home healthcare nurse and chronically ill patients at home can improve patient
      outcome at lower cost than traditional skilled face-to-face home healthcare
      visits.

PMID- 16620168
TI  - Telehealth home health applications for adults with developmental disabilities.
AB  - Telehealth technology for application in home healthcare for adult persons with
      developmental disabilities was examined. Utilization of telehealth by clinicians,
      including the physician, nurse and physician assistant, physical therapist,
      occupational therapist, speech language pathologist, the dietitian, and
      psychologist for the healthcare needs of adults with developmental disabilities
      is discussed. Such utilization results in improved access to needed health
      services by reducing time and distance for this population. A telehealth model is
      offered, as are shifts in healthcare using telehealth technology in home health.

PMID- 16620169
TI  - Monitoring daily living activities of elderly people in a nursing home using an
      infrared motion-detection system.
AB  - We examined whether we could identify activity patterns of elderly people in a
      nursing home from sensor outputs of an infrared monitoring system. The subjects
      consisted of three elderly people. A single passive infrared sensor installed on
      the ceiling of each subject's usual dwelling room provided digital output
      whenever the subject moved. The subjects' actual daily activities were
      established from questionnaires with which patients documented their living
      patterns for each of 7 days. Activities were classed as sleeping, getting
      up/breakfast, indoor activities/going out, and dinner/going to bed. The mean +/-
      2 standard deviations (SDs) of the sensor outputs on each day for each period of
      indoor activity was used to distinguish between normal and aberrant activities.
      Days on which sensor outputs exceeded the means +/- 2 SDs were regarded as
      atypical and were identified for each subject over a 28-day period. We were
      unable to determine the physical condition of the subjects on these atypical
      days. We were able to identify the pattern of daily indoor living activities and
      the duration of each class of activity using sensor outputs and a questionnaire.
      Days were assumed to be atypical when sensor outputs deviated from the normal
      pattern.

PMID- 16620170
TI  - Care coordination and telehealth technology in promoting self-management among
      chronically ill patients.
AB  - With an increasingly complex healthcare system, the need to coordinate the care
      for chronically ill patient often goes unmet. This results in increased
      utilization of services at significant costs. In addition, providing patients
      with the tools to manage their own disease processes over the long term is also
      lacking in the healthcare environment. The Veterans Health Administration (VHA)
      approached these challenges by creating a Care Coordination program using
      technology to promote self management for veterans. Although a relatively new
      program, the Veterans Integrated Services Network (VISN) 7, has shown substantial
      gains in both decreasing the use of high cost care, such as emergency department
      (ED) visits and hospitalizations, as well as improving clinical outcomes with
      better glycemic control for patients with diabetes and improved lipid management
      for all patients.

PMID- 16620171
TI  - Telerehabilitation in spinal cord injury persons: a novel approach.
AB  - The care of a spinal cord injury (SCI) person constitutes a great challenge for
      the provider: SCI persons are mobility impaired, and they are prone to develop
      multiple comorbidities such as diabetes mellitus, hypertension, obesity, bladder
      infections, wounds, and depression. Furthermore, disease manifestations can be
      misleading depending on the level of injury. The utilization of telemedicine to
      monitor patients and deliver care has opened a new horizon for SCI persons.
      Several telehealth programs are now in use to monitor pressure ulcers and
      postdischarge rehabilitation in SCI persons. To answer the need for a more
      comprehensive approach to the multifaceted manifestation of SCI at the James J.
      Peters VAMC, we have started a customized telerehabilitation program. The program
      monitors the most common comorbidities of SCI, it is instrumental in the
      reintegration of the SCI person in the community, it offers individualized in
      home rehabilitation programs, it addresses safety issues, and it offers
      counseling, weight reduction, and maintenance plans. A team of SCI specialists
      including an internist, a registered nurse, a physical therapist, a nutritionist,
      a psychologist, and a recreational therapist-are available for weekly meetings
      with the patients. The programs are tailored to the patients' needs and agreed
      upon by both parties. Both messaging devices and video monitors are utilized. An
      interdisciplinary template is used to record assessments and plans. Preliminary
      results are encouraging; coordination of the team and relative poor technology
      are some of the obstacles we have identified. Further evaluation is necessary to
      determine cost effectiveness.

PMID- 16620172
TI  - Home telehealth special interest group: past, present, and future.
AB  - The American Telemedicine Association (ATA) established the Home Telehealth
      Special Interest Group (SIG) in 1999. Its mission is to support the expansion and
      use of telehealth, remote monitoring and disease management applications in the
      home. The SIG has many areas of interest and has focused on raising public and
      professional awareness about the benefits of home telehealth, developing and
      standardizing clinical guidelines for the delivery of services and advocating for
      reimbursement through state and federal funding. SIG membership has grown
      dramatically, to more than 425 members today. These numbers make it the fastest
      growing and largest of the ATA's Special Interest Groups.

PMID- 16620180
TI  - The epidemiology and prevention of congenital cytomegalovirus infection and
      disease: activities of the Centers for Disease Control and Prevention Workgroup.
AB  - Perhaps no single cause of birth defects and developmental disabilities in the
      United States currently provides greater opportunity for improved outcomes in
      more children than congenital cytomegalovirus (CMV). --Cannon and Davis. BMC
      Public Health 2005;5:70 Each year in the United States, thousands of children and
      their families are affected by congenital cytomegalovirus (CMV) infection. More
      children may be affected by congenital CMV than by other, better known childhood
      conditions, such as Down syndrome, fetal alcohol syndrome, and spina bifida. The
      Centers for Disease Control and Prevention (CDC) has formed a Workgroup on
      Congenital CMV, led by the National Center on Birth Defects and Developmental
      Disabilities and the National Center on Infectious Diseases. This report provides
      background on congenital CMV infection and describes the goals and activities of
      the workgroup for reducing the burden of sequelae of congenital CMV infection.

PMID- 16620181
TI  - Toward optimal health: Sally Wenzel, M.D. Discusses the need for better asthma
      management in women. Interview by Jodi R. Godfrey.

PMID- 16620182
TI  - Evaluation of the first 10 years of the Office of Research on Women's Health at
      the National Institutes of Health: selected findings.

PMID- 16620183
TI  - Public roundtable on future directions in Women's Health Research at the National
      Institutes of Health.

PMID- 16620184
TI  - The causes and consequences of overactive bladder.
AB  - Overactive bladder (OAB) is a syndrome characterized by symptoms of urinary
      urgency with or without urgency urinary incontinence (UUI), usually with
      frequency and nocturia. OAB affects approximately 17% of women in the United
      States and Europe. The causes of OAB, as with many bladder disorders, are
      multifactorial and are not completely understood. The primary functions of the
      lower urinary tract (bladder and bladder outlet mechanism) are storage and
      evacuation of urine. The bladder and the micturition cycle are under complex
      neural control involving both the sympathetic and parasympathetic nervous
      systems. Micturition may occur in response to the activation of receptors in the
      bladder muscle and detection of chemical stimuli by receptors within the bladder
      lining. Neurogenic or myogenic bladder dysfunction can lead to the symptoms of
      urgency, frequency, and UUI that characterize OAB. The consequences of this
      condition are far-reaching and include direct medical consequences and coping
      strategies that adversely affect quality of life. Although the prevalence of OAB
      increases with age, it is not a normal consequence of aging. Antimuscarinic
      agents (e.g., oxybutynin, tolterodine, trospium, solifenacin, and darifenacin)
      have demonstrated efficacy for the treatment of OAB symptoms in multiple clinical
      trials. This review explores the physiological basis for OAB, the effects of OAB
      on health-related quality of life, and the pharmacotherapies that may provide
      relief to patients with this distressing condition.

PMID- 16620185
TI  - Lipid profile and bone paradox: higher serum lipids are associated with higher
      bone mineral density in postmenopausal women.
AB  - BACKGROUND: Previous studies suggest a relationship between cardiovascular
      disease (CVD) and osteoporosis; however, the mechanism of the relationship and
      whether serum lipids are positively or negatively associated with bone mineral
      density (BMD) are unclear. METHODS: We investigated the relationship among serum
      lipids, dietary saturated fat, BMD of various skeletal sites, and markers of bone
      turnover. This was a cross-sectional analysis in 136 Caucasian, healthy,
      postmenopausal women, who were not taking lipid-lowering medications or drugs
      affecting bone metabolism. BMD at multiple skeletal sites was assessed by DXA.
      Concentration of serum triglycerides, cholesterol, osteocalcin (OC), and
      undercarboxylated osteocalcin (UOC) and urinary cross-linked N-telopeptides were
      analyzed by routine methods. Saturated fat, total calcium (food and supplements),
      total vitamin K, alcohol, and energy intake were estimated using 3-day dietary
      records. Physical activity was assessed and used as a confounder with other
      anthropometric measurements. RESULTS: Serum triglycerides were positively related
      to femoral shaft BMD and serum cholesterol to total body BMD (p < 0.05). Also,
      subjects with serum triglycerides above the median had significantly higher BMD
      in femoral Ward's triangle than those below the median (p = 0.037, by ANCOVA).
      Subjects with a serum cholesterol level of > or =240 mg/dL (cutoff for increased
      risk for CVD) had significantly higher BMD at the total body and at all sites of
      the femur (except neck). There was no relationship between serum lipids and
      markers of bone turnover. Saturated fat intake was not associated with BMD of any
      skeletal site. CONCLUSIONS: These findings indicate that higher levels of serum
      triglycerides and cholesterol are positively associated with BMD of various
      skeletal sites. The mechanism of this association is not clear, and studies are
      needed to clarify this relationship.

PMID- 16620186
TI  - The effectiveness of walking in preventing cardiovascular disease in women: a
      review of the current literature.
AB  - This paper summarizes research examining the effects of walking on the prevention
      of cardiovascular disease (CVD) and treatment of CVD risk factors in women.
      Epidemiological evidence indicates that walking reduces a woman's risk for
      developing CVD. Walking may lower CVD risk by having beneficial effects on risk
      factors associated with CVD development. Obesity, dyslipidemia, hypertension, and
      diabetes can all be positively affected by increased physical activity or, more
      specifically, increased daily walking in women. With a large number of people
      living a sedentary lifestyle, it is important to focus on the effects of physical
      activity options that are both physiologically beneficial and personally
      appealing and available to the majority of individuals. With studies showing
      positive results using pedometer- monitored walking to decrease CVD risk,
      accumulated daily walking as opposed to structured walking activity should also
      be considered as a viable option in women.

PMID- 16620187
TI  - Microbicide preference among young women in California.
AB  - BACKGROUND: Microbicides for HIV/sexually transmitted infection (STI) prevention
      are still in development. Microbicide acceptability studies have thus focused on
      soliciting input from individuals about hypothetical products using traditional
      epidemiological and behavioral research methodologies. Here, we integrate a well
      established market research method, conjoint analysis, with more traditional
      epidemiological and behavioral research to examine potential users' preferences
      for different microbicide formulations. METHODS: Focus group discussions (n = 67)
      were held with a diverse population of young men and women (aged 18-32 years)
      from Northern California. Then, young women participated in structured surveys (n
      = 321) that included a conjoint study, a methodology not yet used in microbicide
      acceptability. The main outcome measures were intentions for different
      microbicide formulations, inferred preferences for microbicide characteristics,
      and self-reported risk factors for HIV, other STIs, and pregnancy. RESULTS: Risk
      of STIs and unwanted pregnancies is a concern within this population.
      Participants' responses suggest that the ideal microbicide would (1) offer
      protection from pregnancy, HIV, STIs, and vaginal infections, (2) offer as much
      protection as condoms, (3) allow insertion up to 8 hours prior to sexual
      activity, (4) be available over the counter (OTC), (5) be inserted with an
      applicator, and (6) have only slight leakage not requiring a panty liner. The
      average predicted purchase probability for this ideal microbicide was 69%.
      CONCLUSIONS: Our findings help illustrate microbicide product preferences and
      demand among young women in California, and the methodological approach should
      lend itself to other populations as well as during clinical trials when
      understanding product use and nonuse is critical.

PMID- 16620188
TI  - Antioxidant vitamin supplements and markers of bone turnover in a community
      sample of nonsmoking women.
AB  - BACKGROUND: Whereas several epidemiological studies suggest that low dietary
      intake of vitamins C and E is linked to increased hip fracture in smokers and
      antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women,
      none has demonstrated an effect of supplemental antioxidants on bone turnover.
      METHODS: In an observational study of 533 randomly selected women, we
      investigated the associations among the use of antioxidant supplements, vitamins
      C and E, serum levels of biochemical markers of bone turnover (C-telopeptide
      [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral
      density (BMD). RESULTS: Twenty-two women were identified as current users of
      supplemental vitamin C or E. Duration of antioxidant supplement use was
      negatively associated with age-adjusted and weight-adjusted serum CTx, such that
      mean CTx levels (natural log transformed) were 0.022 units lower for each year of
      exposure. No significant differences were detected for adjusted serum BSAP or
      whole body BMD. CONCLUSIONS: Our results suggest that antioxidant vitamin E or C
      supplements may suppress bone resorption in nonsmoking postmenopausal women.
      Coupling of bone formation and resorption may explain the absence of an effect on
      bone formation markers, given evidence of enhanced effects of antioxidants on
      osteoblast differentiation; this warrants further investigation. This work adds
      to the growing body of evidence that antioxidants may play a role in preventing
      osteoporosis.

PMID- 16620189
TI  - Disease prevalence and use of preventive services: comparison of female veterans
      in general and those with spinal cord injuries and disorders.
AB  - BACKGROUND: Disease prevalence and use of preventive services may differ between
      women veterans in general and those with spinal cord injuries and disorders
      (SCI&D). Prevention is particularly important in SCI&D, and disparities may exist
      in receipt of this care, particularly when special equipment and body adjustments
      are needed, among women with SCI&D. METHODS: To compare disease prevalence and
      preventive service use among female veterans in general and those with SCI&D, we
      conducted a cross-sectional survey among female veterans in general (n = 478) and
      those with SCI&D (n = 115). Behavioral Risk Factor Surveillance System (BRFSS)
      survey questions were administered to veterans with SCI&D and compared with 2003
      CDC BRFSS data. RESULTS: Female veterans with SCI&D were similar in age and race
      but were better educated and less likely to be employed than female veterans in
      general. Coronary heart disease (CHD) prevalence was higher in those with SCI&D
      (17% vs. 8%, p < 0.0001). Health status was lower in SCI&D (27%) than in general
      female veterans (41%), p = 0.002. Fewer women with SCI&D, than female veterans in
      general reported having received recommended dental care (56% vs. 69%, p =
      0.004), colon screening in prior 5 years (59% vs. 72%, p = 0.023) or prior 10
      years (67% vs. 92%, p< 0.0001), mammogram (84% vs. 91%, p = 0.019), and Pap smear
      (88% vs. 98%, p < 0.0001). There were no differences in receipt of respiratory
      vaccinations or cholesterol screening. CONCLUSIONS: Receipt of services that
      require the use of equipment, body adjustments, and potential discomfort due to
      disability was lower in women with SCI&D. Veterans Affairs (VA) is doing well in
      most areas, but there are gaps in receipt of some preventive services. Efforts to
      increase preventive care in women with SCI&D should address equipment and access
      barriers and patient and provider education.

PMID- 16620190
TI  - Profile of ovarian cancer patients seeking information from a web-based decision
      support program.
AB  - BACKGROUND: There is limited information available regarding the characteristics
      of patients who elect to gather and share information about their malignancy on
      the Internet. METHODS: Using a proprietary decision support program embedded into
      a number of established websites, individuals entered personal clinical data into
      disease site profilers designed to provide information about evidence-based
      treatment options, based on specific characteristics (e.g., stage of disease,
      prior therapy) provided by the patients. The aggregate data were evaluated to
      examine the characteristics of patients with gynecological cancer (with a focus
      on newly diagnosed and recurrent ovarian cancer) using such a tool. RESULTS: From
      early 2000 through November 2004, >15,000 patients with gynecological cancer have
      entered data into one of four profilers: newly diagnosed (n = 5604)/recurrent (n
      = 2803) ovarian, endometrial, and cervical cancers. Internal data consistency
      includes similar ages and general health histories of the ovarian and endometrial
      cancer populations and younger age of the cervical cancer patients. Whereas 90%
      of the women with ovarian cancer considered themselves to be in "good health,"
      64% of newly diagnosed vs. only 50% of recurrent disease patients declared their
      activity level was "normal." Of the recurrent patients, 32% stated they had
      undergone a secondary surgery. The overall aggressive management philosophy of
      the recurrent patients in this series is supported by the observation that 33%
      had received > or =4 prior chemotherapy regimens, 97% desired additional
      treatment, and 81% were interested in clinical trials. CONCLUSIONS: Women with
      ovarian cancer seeking assistance from web-based decision support programs may
      represent a subgroup with unique clinical features compared with the general
      patient population.

PMID- 16620191
TI  - Reflections on a decade of experience in implementing a Center for Women's Health
      at an Academic Medical Center.
AB  - On the 10th anniversary of the establishment of a Center for Women's Health (CWH)
      program, the opportunity to share the successes and limitations in developing a
      centralized approach to women's healthcare is provided. The development of the
      CWH at the Columbia University Medical Center, New York-Presbyterian Hospital was
      prompted by concerns that the health status for women is worse than for men in
      terms of disability, morbidity, and chronic illness. Moreover, women move through
      cycles of health and illness differently from men, and gender inequalities in
      research design and implementation and underrepresentation of women in clinical
      studies contributed to knowledge gaps concerning women's health, possibly leading
      to suboptimal care. The goal in developing a program was (1) to provide
      outstanding medical care to women based on prevention and treatment of unique
      aspects of women's health, (2) to develop professional training and
      multidisciplinary educational programs promoting knowledge, understanding, and
      credible scientific efforts, and (3) to foster collaborative research and
      communication among researchers, practitioners, policymakers, and organizations.
      In this paper, the clinical and educational programmatic activities and lessons
      learned are described.

PMID- 16620193
TI  - Disease management interventions II: What else is in the black box?
AB  - The success of any disease management (DM) program ultimately depends upon the
      ability and willingness of participants to change and maintain desired health
      behaviors. To achieve those results, DM program administrators have several
      issues to consider, including the type of behavioral change desired, the scope of
      intervention that the organization is willing and capable of implementing, and
      whether the appropriate support structures are available to ensure successful
      achievement of program goals. An understanding of these issues will assist
      program designers in selecting the appropriate change models. This paper serves
      as an extension of our prior paper in which eight core psychosocial behavioral
      change models were described. Here, five more recently developed theory-based
      approaches are introduced, providing readers with up-to-date information in this
      area.

PMID- 16620194
TI  - The case for disease management in chronic kidney disease.
AB  - Chronic kidney disease (CKD) is a growing epidemic in the United States and
      worldwide, with nearly two thirds of CKD patients also having diabetes,
      hypertension, or both. Morbidity and mortality among patients with CKD are high,
      as are the costs associated with care, which is highly fragmented. Disease
      management (DM) programs are designed to coordinate the delivery of care to
      patients, improve clinical outcomes, and reduce costs along the continuum of
      care. The goals of DM programs in CKD patients are to fill the gaps in current
      care by focusing on four key areas: (1) slowing the progression of CKD, (2)
      identifying and managing the complications of CKD, (3) identifying and managing
      associated comorbid conditions, and (4) smoothing the transition to renal
      replacement therapy (RRT). To be successful, this approach requires
      multidisciplinary collaboration among physicians (eg, primary care physicians,
      endocrinologists, cardiologists, nephrologists, surgeons) and participating
      caregivers including nurses, dieticians, social workers, and pharmacists. Patient
      identification, limited reimbursement, late patient referral, and lack of primary
      care physician and nephrologist knowledge about the importance and details of CKD
      management are all barriers that must be overcome for such programs to be
      successfully implemented. Considering the magnitude of the opportunity, DM
      applied to CKD is a promising approach to the care of this vulnerable population.

PMID- 16620195
TI  - Influences on screening for chronic diabetes complications in type 1 diabetes.
AB  - Screening for the long-term complications of diabetes is a critical component of
      diabetes management; however, evidence demonstrates that screening rates in
      diabetes populations are suboptimal. Our objective was to determine the use and
      predictors of optimal screening behavior, defined as receiving a fasting lipid
      test, dilated eye exam, spot urine test, foot examination, blood pressure
      reading, and hemoglobin A1c (HbA1c) in the previous year in a representative
      cohort of subjects with type 1 diabetes. Data are from the Pittsburgh
      Epidemiology of Diabetes Complications Study, a prospective cohort study of
      subjects with childhood onset type 1 diabetes. Data from 325 participants who
      responded to a survey during 1999-2001 were included in analyses. Reported
      screening rates were as follows: 87.9% had at least one HbA1c measurement in the
      past year, 63% had a foot exam, 73.3% had a spot urine test, 81.9% had a dilated
      eye exam, 93.5% had a blood pressure reading and 68.7% received a fasting lipid
      profile. Within this group, 37.7% of subjects reported undergoing all five tests
      (optimal screening). Independent correlates of optimal screening were receiving
      care from a specialist provider (odds ratio [OR] = 2.4; 95% confidence interval
      [CI]: 1.4-4.1) and blood glucose monitoring at least weekly (OR = 2.6; 95% CI:
      1.1-6.2). These findings indicate that a large proportion of persons with type 1
      diabetes are not being screened at the optimal level. Our data indicate that
      efforts to rectify this should focus on men and those who do not monitor blood
      glucose, and should involve primary care practitioners.

PMID- 16620196
TI  - Transtheoretical model intervention for adherence to lipid-lowering drugs.
AB  - An estimated 60% of individuals prescribed lipid-lowering medications are
      nonadherent. Failure to adhere increases morbidity, mortality, healthcare
      utilization, and healthcare costs. This study examined the effectiveness of a
      population-based, individualized Transtheoretical Model (TTM) expert system
      intervention to improve adherence and increase exercise and diet in a randomized
      18-month trial involving 404 adults. Compared to usual care, treatment
      participants who started in a pre-action stage were significantly more likely to
      be in the Action and Maintenance (A/M) stages for adherence at end of treatment
      (55.3% versus 40%, z = 2.11, p < 0.05, h = 0.31) and at 18-months (56% versus
      37.8%, z = 2.38, p < 0.01, h = 0.36). The treatment group scored significantly
      better on two measures of adherence at six and 12 months post-treatment (all p <
      0.05, odds ratios [OR] 1.49-3.67). Among those who began in A/M, treatment
      participants were significantly more likely to remain in A/M at 18 months (85.2%
      versus 55.6%, z = 2.63, p < 0.01, h = 0.67). Those receiving treatment were
      significantly more likely to progress to A/M for exercise and dietary fat
      reduction (43.3% versus 24.7% for exercise, and 24.7% versus 12.5% for diet). TTM
      expert system interventions can have a significant impact on entire populations
      for adherence. Results for dietary fat and exercise suggest covariation of
      treatment effects.

PMID- 16620197
TI  - Managing the burden of chronic kidney disease.
AB  - Patients with chronic kidney disease (CKD) have high rates of healthcare
      utilization, morbidity, and mortality. Increasing rates of obesity, diabetes, and
      hypertension suggest that the expected numbers of patients with CKD will rise.
      Managing the economic and clinical burden of CKD will be a significant challenge
      for the healthcare system. The burden of CKD can be considered in terms of both
      CKD-specific and CKD-related morbidity and mortality. CKD-specific complications
      include anemia and bone disease. CKD-related complications include obesity,
      diabetes and hypertension. CKD-specific complications tend to occur later in the
      course of disease and may be best treated by a nephrologist, while CKD-related
      complications may be most easily treated by primary care physicians. Coordinating
      patient care is essential to managing the burden of this growing disease.

PMID- 16620198
TI  - The impact of the laboratory on disease management.
AB  - The laboratory has been an integral part of the continuum of care for centuries.
      It has been said that 60%-70% of critical decisions in diagnosis and treatment
      involve quantifiable laboratory data. Disease management (DM) outcomes can be
      influenced through effective use of this information. Today's laboratory supports
      DM in the following ways: disease screening for early identification of disease;
      predictive measures to identify those at risk for a disease; disease
      identification to diagnose and confirm a disease; treatment which can be
      initially identified or changed based upon the results of a lab test; and
      compliance/surveillance to identify whether a treatment is working or if the
      appropriate level of medication has been prescribed for a patient. This paper
      discusses the importance of laboratory testing in all phases of DM.

PMID- 16620199
TI  - Spread of H5N1 avian influenza virus: an ecological conundrum.
AB  - The role of wild birds in the spread of influenza H5N1 virus remains speculative
      and the ecology of influenza A viruses in nature is largely unstudied. There is
      an urgent need for multidisciplinary studies to explore the ecology of avian
      influenza viruses in wild birds and the environment to support ecological
      interpretation of the source of disease outbreaks in poultry.

PMID- 16620200
TI  - Evaluation of an alternative method for the enumeration and confirmation of
      Clostridium perfringens from treated and untreated sewages.
AB  - AIMS: Clostridium perfringens is recommended as a suitable indicator bacterium
      for human enteric viruses, Giardia cysts and Cryptosporidium oocysts in finished
      water and in the assessment and evaluation of water treatment. Several agars and
      confirmation procedures were evaluated in parallel with the Australian/New
      Zealand Standard (AS/NZ) Method for the enumeration of Cl. perfringens from
      treated and untreated sewage samples. METHODS AND RESULTS: The current AS/NZ
      method utilizes tryptose sulfite cycloserine agar (TSC), lactose gelatin medium
      (LG) and nitrate motility medium (NM) at an incubation temperature of 37 degrees
      C. Sixty treated and untreated sewage samples were used to evaluate TSC agar,
      membrane Cl. perfringens agar (mCP), Perfringens agar (OPSP) and Perfringens agar
      with 4-methylumbelliferyl phosphate (OPSP-MUP) for enumeration of Clostridium. An
      incubation temperature of 44 degrees C for 24 h was used for comparison.
      Confirmation procedures were also evaluated using 103 isolates and included LG
      and NM, ortho-nitrophenyl-beta-D-galactopyranoside (ONPG) with MUP (ONPG-MUP) and
      phosphatase reagent (PR). OPSP compared favourably with TSC agar. One false
      negative result was obtained from each of the LG/NM and ONPG-MUP procedures. No
      false results were obtained using the PR confirmation procedure. CONCLUSIONS:
      OPSP agar and PR were determined as suitable replacements for the AS/NZ Standard
      procedure with no interference from spreading organisms. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This is a simple and rapid method for isolating and enumerating Cl.
      perfringens from sewage samples and confirmed results can be reported more
      quickly due to shorter analytical turnaround times.

PMID- 16620201
TI  - Comparison of polymerase chain reaction systems for detection of different cdt
      genes in Escherichia coli strains.
AB  - AIMS: Cytolethal distending toxins (CDT) are tripartite toxins encoded by three
      adjacent or overlapping genes (cdtA, cdtB, cdtC) and found in multiple pathogens.
      The present knowledge regarding heterogeneity of cdt genes and our previous study
      revealed that the available polymerase chain reaction (PCR) systems lack adequate
      specificity. The detection of various cdt genes present in Escherichia coli
      strains, from different geographical regions demands further assays for wide
      range coverage. On the basis of these observations, we were prompted to undertake
      the present study; hence the specificity of existing PCR systems was addressed
      using E. coli prototype strains with known cdt gene sequences. METHODS AND
      RESULTS: A multiplex PCR designed for the detection of E. coli cdt genes was
      found to be sensitive and specific enough for initial screening. However, for
      subtyping, the PCR systems yielded nonspecific products upon amplification. These
      primers are usually designed for sequences of the cdtB locus (the most conserved
      region of the gene), and since CDT-producing E. coli strains carry different cdt
      genes, none of the systems are really type specific. Furthermore, PCR systems
      with type-specific primers for other regions of the gene, i.e. ORF A or ORF C are
      found to be strain specific and their applications in different geographical
      regions have limitations. CONCLUSIONS: In conclusion, based on our observations,
      using these available primers, it seems that the existing PCR systems are not
      sufficiently accurate to differentiate between different types of cdt genes.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results obtained from this study
      revealed that so-far reported PCR systems are short in specificity. These PCR
      protocols were not found to be specific enough to detect various cdt genes and
      have a limited range of application. Moreover, due to similarities in cdt genes
      the cross-reaction between different sets of primers exists. Hence for
      epidemiological studies, some additional PCR protocols are required for screening
      clinical isolates for cdt genes.

PMID- 16620202
TI  - Effects of Lactobacillus strains on cancer cell proliferation and oxidative
      stress in vitro.
AB  - AIMS: The objective of this study was to assess in vitro, whether heat-killed
      (HK) lactic acid bacteria cells and fractionations of HK cells could suppress the
      viability of human cancer cells and inhibit the cytotoxicity associated with
      oxidative stress. METHODS AND RESULTS: Among the strains, the HK cells of
      Lactobacillus acidophilus 606 and Lactobacillus casei ATCC 393 exhibited the most
      profound inhibitory activity in all of the tested cell lines. HK cells of L.
      acidophilus 606 were determined to be less toxic to healthy human embryo
      fibroblasts (hEF cells) than were HK cells of L. casei ATCC 393. The soluble
      polysaccharides from L. acidophilus 606 evidenced the most effective anticancer
      activity, but inhibited hEF cell growth by only 20%. The soluble polysaccharides
      from L. acidophilus 606 were partly observed to induce apoptosis in the HT-29
      cells by DNA fragmentation and propidium iodine staining. Both the HK cells of L.
      acidophilus 606 and the soluble polysaccharide components of this strain also
      exhibited potent antioxidative activity. CONCLUSIONS: Our findings suggest that
      the soluble polysaccharide fraction from L. acidophilus 606 may constitute a
      novel anticancer agent, which manifests a high degree of selectivity for human
      cancer cells and antioxidative agent in the food industry. SIGNIFICANCE AND
      IMPACT OF THE STUDY: These soluble polysaccharide components from Lactobacillus
      may be applied to various foods, and used as adjuncts for cancer therapy and
      prevention.

PMID- 16620203
TI  - Gluten breakdown by lactobacilli and pediococci strains isolated from sourdough.
AB  - AIMS: To evaluate the growth and metabolic activity of lactobacilli and
      pediococci strains in a gluten base medium (GBM), formulated for a proper
      selection of proteolytic strains to be used in sourdough fermentation. METHODS
      AND RESULTS: Proteolytic activity by lactic acid bacteria (LAB) was evaluated by
      SDS-PAGE and by the amino acids released determined by reversed-phase high
      performance liquid chromatography. Only 13 LAB (nine lactobacilli and four
      pediococci), among the 42 evaluated were able to utilize gluten as nitrogen
      source and to grow in GBM. Pediococcus pentosaceus CRL 797 showed a similar
      proteolytic activity to lactobacilli strains. In the majority of the cultures,
      basic amino acid group increased (c. 80% after 12 h incubation) mainly due to the
      release of ornithine, a flavour precursor of bread. Lysine, a limiting essential
      amino acid in wheat flour, increased by 150% in cultures of P. pentosaceus CRL
      797. CONCLUSIONS: This study allows selecting P. pentosaceus CRL 797 and L.
      plantarum CRL 759 as potential starter culture for type III sourdough
      fermentation. It is shown for the first time that pediococci strains isolated
      from sourdough are proteolytically active on gluten. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The physiological studies on gluten breakdown by LAB will contribute
      to the better selection of strains to produce breads with enhanced organoleptic
      characteristics.

PMID- 16620204
TI  - Effect of the addition of inert cellulose substrates to grape must on
      Saccharomyces cerevisiae diversity and the evolution of alcoholic fermentation.
AB  - AIMS: To study the addition of cellulose-based adjuvant as a resource to offset
      the negative effects produced by grape juice clarification during alcoholic
      fermentations. METHODS AND RESULTS: The effect of the addition of two kinds of
      inert cellulose substrates in white wine vinification was investigated in two
      different musts. In one of these musts, stuck fermentations were detected. One of
      the types of cellulose examined had a fining effect, which caused a decrease in
      the number of viable yeasts in the medium and altered the distribution and
      frequency of the clones, which performed the fermentation. The other cellulose
      substrate made the medium cloudier but did not alter the distribution of yeasts
      in comparison with the control. CONCLUSIONS: The behaviour of the inert cellulose
      substrates on vinification depends on its physical characteristics and its
      capacity for making the must cloudy. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      addition of inert cellulose substrates in white wine vinification improves the
      fermentation process and the quality of wines obtained. This effect is more
      noticeable in difficult fermentations. One variety of cellulose showed an
      inhibitory effect on Torulaspora delbrueckii yeasts.

PMID- 16620205
TI  - Gene expression of Corynebacterium glutamicum in response to the conditions
      inducing glutamate overproduction.
AB  - AIM: The ultimate aim is to elucidate the molecular mechanisms for glutamate
      overproduction by Corynebacterium glutamicum. METHODS AND RESULTS: Gene
      expression in response to the conditions inducing glutamate overproduction was
      investigated by using a DNA microarray technique. Most genes involved in the EMP
      pathway, the PPP, and the TCA cycle were downregulated, while five genes that
      were highly upregulated (NCgl0917, NCgl2944, NCgl2945, NCgl2946, and NCgl2975)
      were identified under all the three conditions for overproduction that are
      studied here. Gene products of NCgl2944, NCgl2945, and NCgl2946 were highly
      homologous to each other, did not resemble any other protein, and have remained
      uncharacterized thus far. The product of NCgl0917 showed a similarity to a few
      hypothetical and uncharacterized proteins. NCgl2975 was homologous to metal
      binding proteins. CONCLUSIONS: The decrease in the activity of 2-oxoglutarate
      dehydrogenase complex, a key enzyme that is downregulated during glutamate
      overproduction, can be mainly attributed to the downregulation of odhA and sucB.
      Five highly upregulated genes were also identified. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Although fermentative production of glutamate has been carried out for
      more than 45 years, information on the molecular mechanisms of glutamate
      overproduction is still limited. This study further elucidates these mechanisms.

PMID- 16620206
TI  - Production of exopolysaccharides by Agrobacterium sp. CFR-24 using coconut water 
      a byproduct of food industry.
AB  - AIMS: The work is intended to explore the suitability of underutilized coconut
      water (a byproduct of food industry) for the production of exopolysaccharides
      (EPS) by Agrobacterium sp. CFR 24. METHODS AND RESULTS: Besides checking the
      suitability of coconut water for the production of water-soluble (WS) and water
      insoluble (WIS) EPS, certain fermentation parameters, such as initial pH,
      incubation period and kinetics of EPS production were investigated. The coconut
      water medium was found to support the production of both types of EPS. The
      optimal initial pH and temperature was found to be 6.0 and 30 degrees C,
      respectively. In shake flask (150 rev min(-1)) studies, high-cell density
      inoculum resulted in the production of 11.50 g l(-1) of WIS-EPS and 4.01 g l(-1)
      WS-EPS after 72 and 96 h of fermentation, respectively. CONCLUSIONS: Coconut
      water was found suitable for the production of microbial EPS by Agrobacterium sp.
      CFR 24 strain. Under optimum conditions, it produced a good amount of WIS-EPS,
      which is comparable with that of the sucrose medium (11 g l(-1)). SIGNIFICANCE
      AND IMPACT OF THE STUDY: This is the first report on the use of coconut water as
      a fermentation medium for the production of any microbial EPS. Besides producing
      value-added products, use of this food industry byproduct, which is often being
      drained out, can significantly reduce the problem of environmental pollution.

PMID- 16620207
TI  - Comparative analysis of phenotypic and genotypic characteristics of two
      desulfurizing bacterial strains, Mycobacterium phlei SM120-1 and Mycobacterium
      phlei GTIS10.
AB  - AIM: To compare few phenotypic and genotypic characteristics of two desulfurizing
      bacterial strains, Mycobacterium phlei SM120-1 and Mycobacterium phlei GTIS10.
      METHODS AND RESULTS: In the present study, dibenzothiophene (DBT) desulfurizing
      activity, composition of fatty acids of cell membranes, DBT sulfone monoxygenase
      gene (bdsA) and the selection pressure applied during the growth and enrichment
      of the bacterial strains M. phlei SM120-1 and M. phlei GTIS10 were compared in
      our laboratory. The DBT desulfurization activity of M. phlei SM120-1 was found to
      be 0.17 +/- 0.02 micromol 2-HBP min(-1) (gram dry cell weight)(-1) and that of
      the bacterial strain M. phlei GTIS10 was 1.09 +/- 0.05 micromol 2-HBP min(-1)
      (gram dry cell weight)(-1). Fatty acid methyl ester analysis of cell membranes of
      these two bacterial strains in the presence of light gas oil showed that both the
      strains had different fatty acid profiles in their cell membranes. Comparison of
      the full gene sequences of the desulfurization gene bdsA in the two bacterial
      strains showed significant difference in the bdsA gene sequences. There was a
      significant difference observed in the selection pressure applied during the
      growth and enrichment of the two bacterial strains. CONCLUSIONS: The results of
      the comparative study of the bacterial strains, M. phlei SM120-1 and M. phlei
      GTIS10 showed that there were considerable differences in the phenotypic and
      genotypic characteristics of these two strains. SIGNIFICANCE AND IMPACT OF STUDY:
      The present study would broaden the understanding of biodesulfurization trait at
      intra-species level.

PMID- 16620208
TI  - Comparison of agar plate and real-time PCR on enumeration of Lactobacillus,
      Clostridium perfringens and total anaerobic bacteria in dog faeces.
AB  - AIMS: To compare agar plate and real-time PCR methods on enumeration of total
      anaerobic bacteria, Lactobacillus and Clostridium perfringens in dog faeces.
      METHODS AND RESULTS: Thirty-two faecal specimens from Labrador retriever dogs
      were used to compare agar plate and real-time PCR enumeration methods for
      Lactobacillus, C. perfringens and total anaerobic bacteria. Total anaerobic
      bacteria, C. perfringens and Lactobacillus of faeces were counted (as CFU g(-1)
      faeces) for 48-h incubation at 37 degrees C in an anaerobic gas chamber on genus
      selective media. Total genomic DNA from samples was extracted by the QIAamp DNA
      stool mini kit. The quantification of DNA (as DNA copy per gram faeces) by real
      time PCR was performed with a LightCycler system with the QuantiTect SYBR green
      PCR kit for PCR amplification. The results indicated that there was a significant
      correlation between CFU and DNA copy of Lactobacillus (R2 = 0.78, P < 0.01) and
      total anaerobic bacteria (R2 = 0.21, P < 0.05); but no correlation was found
      between CFU and DNA copy of C. perfringens. The regression equations for
      Lactobacillus and total anaerobic bacteria were log(DNA copy) = 0.83 x log(CFU) +
      1.43 and log(DNA copy) = 1.62 x log(CFU) - 6.32 respectively. CONCLUSIONS: The
      real-time PCR method could be used to enumerate Lactobacillus within 2 days when
      compared with plating method which requires 5-6 days. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The real-time PCR method and the primer set for Lactobacillus spp.
      harboured in the dog intestine can be used for rapid enumeration of lactobacilli
      and monitoring of the faecal Lactobacillus community.

PMID- 16620209
TI  - Influence of phenol on the biodegradation of pyridine by freely suspended and
      immobilized Pseudomonas putida MK1.
AB  - AIMS: To study the effect of co-contaminants (phenol) on the biodegradation of
      pyridine by freely suspended and calcium alginate immobilized bacteria. METHODS
      AND RESULTS: Varying concentrations of phenol were added to free and calcium
      alginate immobilized Pseudomonas putida MK1 (KCTC 12283) to examine the effect of
      this pollutant on pyridine degradation. When the concentration of phenol reached
      0.38 g l(-1), pyridine degradation by freely suspended bacteria was inhibited.
      The increased inhibition with the higher phenol levels was apparent in increased
      lag times. Pyridine degradation was essentially completely inhibited at 0.5 g l(
      1) phenol. However, immobilized cells showed tolerance against 0.5 g l(-1) phenol
      and pyridine degradation by immobilized cell could be achieved. CONCLUSIONS: This
      works shows that calcium alginate immobilization of microbial cells can
      effectively increase the tolerance of P. putida MK1 to phenol and results in
      increased degradation of pyridine. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Treatment of wastewater stream can be negatively affected by the presence of co
      pollutants. This work demonstrates the potential of calcium alginate
      immobilization of microbes to protect cells against compound toxicity resulting
      in an increase in pollutant degradation.

PMID- 16620210
TI  - Optimization of physical parameters for exo-biopolymer production in submerged
      mycelial cultures of two entomopathogenic fungi Paecilomyces japonica and
      Paecilomyces tenuipes.
AB  - AIMS: In the present study, two different optimization techniques were used to
      determine the suitable operating parameters for exo-biopolymer production in
      submerged mycelial cultures of two entomopathogenic fungi Paecilomyces japonica
      and Paecilomyces tenuipes. METHODS AND RESULTS: First, the rotating simplex
      method, a nonstatistical optimization technique, was employed to obtain the best
      combination of physical parameters (viz. pH, agitation intensity, aeration rate)
      for maximum exo-biopolymer production by P. japonica in a batch bioreactor. The
      optimal combination was determined to be a pH of 8.06, an aeration of 3 vvm,
      without any impeller agitation, producing a 17-time increase in exopolymer
      production (34.5 g l(-1)) when compared with that achieved in unoptimized flask
      cultures. Second, the uniform design method, a statistical optimization
      technique, was employed to determine the best operating parameters for submerged
      culture of P. tenuipes. The optimal combination for mycelial growth was
      determined to be a pH of 4.88, an aeration of 2 vvm and an agitation of 350 rpm,
      while a pH of 4, an aeration of 2 vvm and an agitation of 150 rpm was best for
      exo-biopolymer production. CONCLUSIONS: The exo-biopolymer production in P.
      japonica optimized by the rotating simplex method was strikingly improved (max.
      34.5 g l(-1)), and the exo-biopolymer production in P. tenuipes optimized by the
      uniform design method was also significantly increased (max. 3.4 g l(-1)).
      SIGNIFICANCE AND IMPACT OF THE STUDY: The successful application of these two
      different optimization techniques in this study implies that these methods are
      worthy of applying to other fermentation systems for the production of bioactive
      mycelial biomass and exo-biopolymers in liquid culture of higher fungi.

PMID- 16620211
TI  - Modelling the work to be done by Escherichia coli to adapt to sudden temperature
      upshifts.
AB  - AIMS: This paper studies and models the effect of the amplitude of a sudden
      temperature upshift DeltaT on the adaptation period of Escherichia coli, in terms
      of the work to be done by the cells during the subsequent lag phase (i.e., the
      product of growth rate mumax and lag phase duration lambda). METHODS AND RESULTS:
      Experimental data are obtained from bioreactor experiments with E. coli K12
      MG1655. At a predetermined time instant during the exponential growth phase, a
      sudden temperature upshift is applied (no other environmental changes take
      place). The length of the (possibly) induced lag phase and the specific growth
      rate after the shift are quantified with the growth model of Baranyi and Roberts
      (Int J Food Microbiol 23, 1994, 277). Different models to describe the evolution
      of the product lambda x mumax as a function of the amplitude of the temperature
      shift are statistically compared. CONCLUSIONS: The evolution of lambda x mumax is
      influenced by the amplitude of the temperature shift DeltaT and by the normal
      physiological temperature range. As some cut-off is observed, the linear model
      with translation is preferred to describe this evolution. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This work contributes to the characterization of microbial lag
      phenomena, in this case for E. coli K12 MG1655, in view of accurate predictive
      model building.

PMID- 16620212
TI  - In vitro activities of antibiotics and antimicrobial peptides against the plant
      pathogenic bacterium Xylella fastidiosa.
AB  - AIMS: The objective of this study was to evaluate the effectiveness of
      antibiotics and antimicrobial peptides against 10 strains of Xylella fastidiosa.
      METHODS AND RESULTS: The minimal inhibitory concentration (MIC) of 12 antibiotics
      and 18 antimicrobial peptides were determined by agar dilution tests and growth
      inhibition assays. Antibiotics with the lowest MIC for X. fastidiosa strains were
      gentamicin, tetracycline, ampicillin, kanamycin, and novobiocin, chloramphenicol,
      and rifampin. Plate growth inhibition assays showed that four of the
      antimicrobial peptides (Magainin 2, Indolicidin, PGQ, and Dermaseptin) were toxic
      to all X. fastidiosa strains. CONCLUSION: All X. fastidiosa strains were
      sensitive to several groups of antibiotics, and minor differences in sensitivity
      to several antimicrobial peptides were observed among strains. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study shows that antibiotics and antimicrobial peptides
      have some activity against the pathogen, X. fastidiosa and may have application
      in protecting plants from developing Pierce's disease.

PMID- 16620213
TI  - Molecular level damages of low power pulsed laser radiation in a marine bacterium
      Pseudoalteromonas carrageenovora.
AB  - AIM: To study the molecular level damages in a marine bacterium,
      Pseudoalteromonas carrageenovora, exposed to low power pulsed laser radiation
      from an Nd:YAG laser. METHODS AND RESULTS: The laser damages in bacterial DNA
      were monitored by studying the formation of apurinic/apyrimidinic (AP) sites.
      Molecular probe kits were used for this purpose. Occurrence of lesions in the
      cell walls was monitored under a transmission electron microscope (TEM). The
      results showed that laser radiation significantly increased the number of AP
      sites in the bacterial DNA. This increase corresponded to the laser fluence (J
      cm(-2)) and to the duration of laser irradiation. TEM observation showed the
      occurrence of lesions in bacterial cell walls upon laser irradiation.
      CONCLUSIONS: It is concluded that bacteria exposed to laser irradiation suffers
      DNA damages and resulted in broken cell walls. These events led to bacterial
      mortality. These are in addition to the mechanisms reported earlier such as the
      photochemical reactions occurring inside the cells upon exposure to low power
      laser. SIGNIFICANCE AND IMPACT OF THE STUDY: These results help us to understand
      the mechanisms of bacterial mortality on exposure to low power pulsed laser
      irradiation and are useful in formulating a laser treatment strategy to kill
      bacteria.

PMID- 16620215
TI  - The effect of an antibacterial washing-up liquid in reducing dishwater aerobic
      plate counts.
AB  - AIMS: To assess any significant differences in the aerobic plate count (APC) of
      catering dishwaters following the use of a traditional, nonantibacterial or an
      antibacterial washing-up liquid. METHODS AND RESULTS: A dishwashing trial was
      undertaken within a commercial restaurant of 6 weeks duration (3 weeks with each
      washing-up liquid in a randomized, weekly pattern). Five replicate samples were
      taken from the dishwater at the end of the washing-up operation, on three
      separate occasions each day corresponding to mid-morning, lunchtime and mid
      afternoon meal preparations. CONCLUSIONS: The antibacterial product was shown to
      significantly reduce the APC by an average log10 reduction of 1.81 CFU ml(-1)
      (98.5%) as compared with the traditional product. APC were lower for each of the
      three weekly time periods for the antibacterial product. Continued use of the
      antibacterial product did not decrease the APC of the dishwater, though with the
      traditional product, dishwater counts increased throughout the trial week.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Antibacterial washing-up liquids, with
      proven activity in controlling levels of microorganisms in dishwaters, could play
      a significant role in reducing the risk of cross-contamination between washed
      articles during washing-up operations.

PMID- 16620214
TI  - Nutritional deprivation increases intracellular phosphate and polyphosphate in
      poultry litter microflora.
AB  - AIMS: To determine if mixed microflora from poultry litter accumulates phosphate
      when deprived of carbon and energy or nitrogen sources. METHODS AND RESULTS:
      Microbial enrichments from poultry litter capable of metabolizing ammonia, amino
      acids, and glucose were subjected to nutritional deprivation and the effects on
      intracellular phosphate levels were determined. Results indicate deprivation of
      glucose yields a 38 and 50% increase in intracellular phosphate and polyphosphate
      levels, respectively. Deprivation of nitrogen sources did not result in
      significant intracellular phosphate accumulation. CONCLUSIONS: Micro-organisms
      normally present in poultry litter respond to carbohydrate deprivation by
      accumulating intracellular phosphate. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Poultry litter typically contains significant levels of phosphate which
      contribute to environmental pollution when applied to land. Phosphate is highly
      mobile in soils and often drains into local watersheds following rain events.
      This study raises the possibility that poultry litter micro-organisms may have
      the capacity to sequester phosphate, which could delay or diminish phosphate run
      off.

PMID- 16620216
TI  - Composition of the sheath produced by the green alga Chlorella sorokiniana.
AB  - AIMS: To investigate the chemical characterization of the mucilage sheath
      produced by Chlorella sorokiniana. METHODS AND RESULTS: Algal mucilage sheath was
      hydrolysed with NaOH, containing EDTA. The purity of the hydrolysed sheath was
      determined by an ATP assay. The composition of polysaccharide in the sheath was
      investigated by high-performance anion-exchange chromatography with pulsed
      amperometric detection. Sucrose, galacturonic acid, xylitol, inositol, ribose,
      mannose, arabinose, galactose, rhamnose and fructose were detected in the sheath
      as sugar components. Magnesium was detected in the sheath as a divalent cation
      using inductively coupled argon plasma. The sheath matrix also contained protein.
      CONCLUSIONS: It appears that the sheath is composed of sugars and metals.
      Mucilage sheath contains many kinds of saccharides that are produced as
      photosynthetic metabolites and divalent cations that are contained in the culture
      medium. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on
      chemical characterization of the sheath matrix produced by C. sorokiniana.

PMID- 16620217
TI  - Development of a highly sensitive nested-PCR method using a single closed tube
      for detection of Fusarium culmorum in cereal samples.
AB  - AIMS: The aim of the study was to develop a sensitive detection method of
      Fusarium culmorum contamination in cereal samples. METHODS AND RESULTS: A nested
      PCR method using a single closed tube was developed for the detection of F.
      culmorum in infected cereal samples. The concentrations of the first primer pair
      was diluted 10,000 times compared to the concentration used for the second primer
      pair. Differing annealing temperatures allowed both first and second polymerase
      chain reaction (PCR) reactions to be performed subsequently in the same closed
      tube. The detection limit was 5-50 fg of purified target DNA and allowed the
      detection of 1% infected seeds of wheat in a mixture with uninfected grains.
      CONCLUSIONS: F. culmorum can be specifically detected in cereal samples by the
      highly sensitive method of nested-PCR in a single closed tube. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This work describes the detection of F. culmorum in cereal
      samples that is approximately 100 times more sensitive than previous PCR methods,
      involves low risk of cross contaminations between samples, low costs and reduced
      hands-on time as compared to standard nested-PCR protocols.

PMID- 16620218
TI  - Keratin 17 mutation in pachyonychia congenita type 2 patient with early onset
      steatocystoma multiplex and Hutchinson-like tooth deformity.
AB  - Pachyonychia congenita type 2 (PC-2) is an autosomal dominant disorder
      characterized by hypertrophic nail dystrophy, focal keratoderma, multiple
      pilosebaceous cysts, and other features of ectodermal dysplasia. It has been
      demonstrated that PC-2 is caused by mutations in the keratin 17 and keratin 6b
      genes. In this report, we describe a missense mutation in the keratin 17 gene,
      M88T, in a Korean patient whose phenotype included early onset steatocystoma
      multiplex and Hutchinson-like tooth deformities along with other typical features
      of PC-2 such as hypertrophic nails, natal teeth and follicular hyperkeratosis.

PMID- 16620219
TI  - A Chinese-Japanese boy with black dot ringworm due to Trichophyton violaceum.
AB  - A 4-year and 8-month-old Chinese-Japanese boy, who had been visiting Dalian,
      China frequently, developed multiple alopecia lesions 1 year previously. At his
      initial visit to our department, multiple patchy alopecia with black dots was
      observed in the parietal scalp area. Multiple erythematous macules were also seen
      on the face, nape and right dorsum of the hand. A diagnosis of tinea capitis and
      tinea corporis was obtained on the basis of potassium hydroxide (KOH) microscopic
      examination of hair and scales from the lesions. Colonies grown on Sabouraud
      cycloheximide-chloramphenicol agar culture were examined using Fungi-Tape and
      MycoPerm-blue, and numerous microconidia and a small number of macroconidia were
      observed. Trichophyton violaceum was identified as the causative organism on the
      basis of colony morphology, microscopic morphology and molecular biology
      technique. As T. violaceum infection is not often seen in Japan, we suspected
      that the patient was infected by T. violaceum during his stay in Dalian. Conidia
      formation is rarely observed with T. violaceum, and only five cases with T.
      violaceum macroconidia formation have been reported in Japan (including this
      case). We also report the method for visualizing conidia formation of T.
      violaceum using Fungi-tape and MycoPerm-blue.

PMID- 16620220
TI  - Calcifying aponeurotic fibroma of the knee: A case report with radiological
      findings.
AB  - Calcifying aponeurotic fibroma is a rare type of benign tumor that occurs most
      commonly in the distal extremities of young children. Due to its infiltrative
      growth, it has a high tendency of recurrence. Although the clinicopathological
      features of over 100 cases of this rare disease have been reported, its clinical
      and radiological features have yet to be described in detail. We present a case
      of calcifying aponeurotic fibroma of the knee from birth with radiological
      images, that demonstrate the peculiar features of this uncommon benign tumor and
      discuss its clinicopathological features based on computed tomography and
      magnetic resonance images.

PMID- 16620221
TI  - Cross-reactivity among shrimp, crab and scallops in a patient with a seafood
      allergy.
AB  - Shrimp is known to be the most common causative agent in seafood allergy.
      Patients with shrimp allergy often exhibit allergic symptoms to a variety of
      seafoods such as crabs and clams. We experienced a 14-year-old girl with shrimp
      allergy who developed oral swelling and pain accompanied with an uncomfortable
      feeling after ingestion of scallops followed by intensive exercise. Laboratory
      investigation showed that she had serum immunoglobulin (Ig)E molecules reacting
      with several kinds of crustaceans and mollusks, including shrimp, crab and
      scallops. Immunoblotting revealed that her serum IgE reacted with the 38 kDa
      bands for shrimp, crab and scallops, suggesting that tropomyosin was the major
      allergen. Dot-blot inhibition analysis showed a cross-reactivity among shrimp,
      crab and scallops. We conclude that the cross-reactivity of IgE in this patient
      resulted from the high homology of tropomyosins.

PMID- 16620222
TI  - Transient acantholytic dermatosis (Grover's disease) in a renal transplant
      patient.
AB  - Grover's disease ("transient acantholytic dermatosis") is a transient dermatosis
      of unknown cause manifesting clinically as a papular skin eruption located
      usually on the anterior chest and abdomen and histologically with dyskeratosis
      and acantholysis. Grover's disease has occasionally been reported in patients
      with chronic renal failure, HIV infection, hematological malignancies and bone
      marrow allotransplantation. We report herein a new case of Grover's disease that
      developed in a renal transplant patient. To the best of our knowledge, this is
      the first observation of Grover's disease developing in the setting of solid
      organ transplantation.

PMID- 16620223
TI  - A very large, rapidly developing, congenital giant cell fibroblastoma in a 5
      month old infant.
AB  - Giant cell fibroblastoma is an uncommon soft tissue neoplasm that occurs in
      childhood. It seems to be the juvenile form of dermatofibrosarcoma protuberans,
      which is seen less frequently in children. Only one congenital case has been
      reported previously. In this report, we present a 5-month-old girl with a rapidly
      and atypically growing mass located on the upper part of the right scapula. We
      think that our case is very interesting, because no similarly large lesion (12 cm
      x 10 cm x 8 cm) related to giant cell fibroblastoma has been previously reported
      in the published work.

PMID- 16620224
TI  - A case of lupus erythematosus/lichen planus overlap syndrome.
AB  - A case of lupus erythematosus/lichen planus overlap syndrome (LE/LP overlap
      syndrome) was reported. A 53-year-old woman developed violaceous erythema around
      the nostrils and the upper lips and atrophic scaly erythema on the cheeks and
      neck. Histopathological studies revealed that the patient had distinct discoid
      lupus erythematosus (DLE), LP, and a lesion with combined features of DLE and LP.
      Direct immunofluorescent (DIF) studies of the mixed lesion revealed both
      prominent immunoglobulin (Ig)G deposits in a granular pattern at the basement
      membrane zone (BMZ) and IgM deposits in the clusters of cytoid bodies; the former
      are more typical of LE and the latter more of LP. DIF features in combination
      were unique for LE/LP overlap syndrome. The patient was satisfactorily treated
      with topical tacrolimus. While reports support the effectiveness of tacrolimus in
      either LE or LP, this is the first case of LE/LP overlap syndrome treated with
      topical tacrolimus.

PMID- 16620225
TI  - A case of genital folliculosebaceous cystic hamartoma with an unique aggregated
      manifestation.
AB  - Folliculosebaceous cystic hamartoma (FCH) is a recently recognized cutaneous
      hamartoma composed of follicular, sebaceous and mesenchymal components, and
      usually occurring on the head and neck. We describe herein a case of FCH with an
      unique aggregated manifestation in a genital lesion. The patient was a 40-year
      old woman with a genital lesion composed of a pedunculated nodule, a dome-shaped
      nodule and a subcutaneous nodule, measuring 5 cm in the greatest dimension. The
      largest, pedunculated nodule was histologically composed of an infundibulo-cystic
      structure with follicular, sebaceous and mesenchymal elements accompanied by
      cystic structures of various sizes lined by stratified squamous epithelium and
      follicular germinative cells suggesting follicular cysts. The dome-shaped nodule
      consisted of anastomosing strands of epithelial cells with follicular components.
      The subcutaneous nodule had two components, an infundibulo-cystic structure and a
      cyst lined by squamous epithelium. In our case, the unusual clinical feature of
      large and multiple nodules was due to the presence of several prominent
      hamartomatous cystic structures with FCH. This is the third case of giant FCH.
      The clinical presentation and location of giant FCH is unusual.

PMID- 16620226
TI  - A case of crusted scabies with a bullous pemphigoid-like eruption and nail
      involvement.
AB  - We report a case of a 71-year-old man infected at a nursing home who developed a
      bullous pemphigoid-like eruption with nail involvement. He was diagnosed by his
      family doctor as suffering from eczema and was treated with topical
      corticosteroids, then blisters started appearing. He was next diagnosed as
      suffering from bullous pemphigoid and treated with oral prednisolone, which
      worsened his condition. He was finally diagnosed as having crusted scabies with
      bullous pemphigoid-like eruptions and nail involvement at our clinic. He was then
      prescribed oral ivermectin (two doses of 12 mg ivermectin with a 1-week interval)
      and topical lindane (1%gamma-BHC in petrolatum) for scabies with 5% salicylic
      acid in plastibase as an additional treatment for the crusted lesions on his
      soles. He showed remarkable improvement in 2 weeks, and his nails showed complete
      recovery after 7 weeks of occlusive dressing treatment with 1%gamma-BHC. One and
      a half years later, the patient showed no sign of a recurrence of scabies. The
      histology of a blister taken from this patient was similar to that of bullous
      pemphigoid. Direct immunofluorescence showed immunoglobulin (Ig)G and C3
      deposition at the dermoepidermal junction similar to that of bullous pemphigoid,
      but indirect immunofluorescence was negative. The bullous symptoms of this
      patient were considered to be due to the scabies, because the patient recovered
      completely after receiving treatment for scabies. Indirect immunofluorescent
      study is important to distinguish between scabies with blister formation and true
      bullous pemphigoid.

PMID- 16620227
TI  - Chondrolipoma of the popliteal fossa and Japanese reports.
AB  - A rare case of chondrolipoma of the right popliteal fossa in a 24-year-old female
      was reported with review of the Japanese published work. Eleven patients with
      chondrolipoma including lipoma with cartilaginous metaplasia, including my case,
      have been reported in Japan. The patients ranged in age from 7-79 years. All
      cases occurred in adults except for one. Six patients were male and five were
      female. Two lesions each arose on the tongue, upper back and popliteal fossa, and
      one each on the buccal submucosa, shoulder, breast, lateral chest and sole. The
      duration of the lesions ranged from 1 month to 20 years. The lesions ranged 1-10
      cm in greatest dimension. The presented tumor was an early one because of the
      shortest duration and the smallest size in Japan. Recent criteria for a benign
      mesenchymoma including a chondrolipoma were also described.

PMID- 16620228
TI  - Scleromyxedema: An experience using treatment with systemic corticosteroid and
      review of the published work.
AB  - Scleromyxedema, a rare cutaneous mucinosis of unknown cause, is a variant of
      generalized papular mucinosis that is also known as generalized lichen
      myxedematosus. It is characterized clinically by generalized papular or
      scleroderma-like eruptions. Histopathological examination reveals mucin
      deposition and a proliferation of fibroblasts in the upper dermis. We describe
      the case of a man with scleromyxedema treated with systemic corticosteroids whose
      skin lesions improved gradually within 4 weeks.

PMID- 16620229
TI  - Autoerythrocyte sensitization syndrome associated with grief complications.
AB  - The clinical presentation of a patient with autoerythrocyte sensitization
      syndrome associated with a complicated grief reaction is reported. A 50-year-old
      female patient presented with recurrent episodes of painful ecchymotic bruising
      on the lower extremities which started in 1995 after the sudden death of her son
      and exacerbated almost every year at approximately the same time her son died as
      an anniversary reaction. No pathological findings were detected in the laboratory
      examinations. The diagnosis was confirmed by induction of similar lesions by i.d.
      injection of the patient's own washed erythrocytes and whole blood. Psychiatric
      assessment revealed that the patient was depressed, socially introverted, overly
      defensive and avoidant in interpersonal relationships. Antidepressant treatment
      and psychotherapy for major depression and grief complications were started with
      the patient. Having an awareness of this rare condition will assist in the
      prevention of unnecessary investigations in such cases and will allow early
      referral for appropriate psychological counseling.

PMID- 16620230
TI  - Lipoid proteinosis: A case with ophthalmological and psychiatric findings.
AB  - Lipoid proteinosis (LP) is an uncommon, recessively inherited disorder. The
      disease usually has its onset in the newborn period and is manifested by
      hoarseness. The skin and mucous membrane involvement arises between the first and
      second year of age. A 14-year-old male presented with the complaint of blistering
      on various sites of his skin, from the age of 12 months, resulting in scarring.
      Ophthalmological and psychiatric findings also appeared during the clinical
      course. The histological findings of skin biopsy included extensive deposits of
      amorphous eosinophilic material in the papillary dermis. No known therapy exists
      for LP.

PMID- 16620231
TI  - PHACES syndrome presenting as hemangiomas, sternal clefting and congenital
      ulcerations on the helices.
AB  - Sternal malformation/vascular dysplasia association is a very rare condition
      comprised of midline defects and hemangiomas of the face and anterior trunk, that
      can be found as part of the PHACES phenotypic spectrum (posterior fossa
      malformations, hemangiomas, arterial anomalies, coarctations of the aorta,
      cardiac defects and eye abnormalities, sternal clefting). Herein, we describe a 6
      month-old boy with sternal cleft, extensive segmental hemangiomas, and a
      depigmented scar on the tip of the xyphoid process, corresponding to a sternal
      malformation/vascular dysplasia association. He also had bilateral cutaneous
      ulcerations on the helices. Our case report indicates that ulceration of a
      hemangioma can occur before significant proliferation and may even be present
      congenitally.

PMID- 16620232
TI  - A case of maxacalcitol-resistant confluent and reticulated papillomatosis
      successfully treated with minocycline.

PMID- 16620233
TI  - A case of EEC syndrome with peri/intraoral papillomatosis and widespread
      freckling.

PMID- 16620234
TI  - Good cosmesis of a large rhinophyma after carbon dioxide laser treatment.

PMID- 16620235
TI  - A case of pseudochromhidrosis due to dihydroxyacetone.

PMID- 16620236
TI  - Topical tacrolimus for pyoderma gangrenosum: Another report.

PMID- 16620237
TI  - Postherpetic paresis of the lower limb.

PMID- 16620238
TI  - Prevention of postoperative pressure ulcers by a polyurethane film patch.

PMID- 16620240
TI  - Is evidence-based nursing practice an attainable goal?

PMID- 16620241
TI  - Breastfeeding support and early cessation.
AB  - OBJECTIVE: To examine the types of help women received with breastfeeding both in
      the hospital and at home and the reasons why women stopped breastfeeding earlier
      than intended. DESIGN: A descriptive design with open-ended questions. SETTING:
      After participant recruitment in the postpartum hospital room, data were
      collected by phone 8 weeks after delivery. PATIENTS/PARTICIPANTS: Three hundred
      seventy-nine women planning to breastfeed for at least 8 weeks after
      uncomplicated delivery. MAIN OUTCOME MEASURES: Breastfeeding status at 8 weeks
      postpartum; report of help with breastfeeding in the hospital and at home.
      RESULTS: Sixty-eight percent of women were still breastfeeding at 8 weeks,
      although 37% of those reported supplementing with formula. Of those who had
      stopped, the most common reason was insufficient milk supply. Other reasons
      included painful nipples and latch problems, personal reasons, returning to work
      or school, and drugs/illness of the mother or baby. Most women received help with
      breastfeeding in the hospital, but only 55% received help with breastfeeding
      after hospital discharge. CONCLUSIONS: The primary reasons for early cessation of
      breastfeeding are amenable to nursing intervention. Every opportunity should be
      taken to address these issues both in the hospital and through follow-up calls.

PMID- 16620242
TI  - Black non-Hispanic mothers' perceptions about the promotion of infant-feeding
      methods by nurses and physicians.
AB  - OBJECTIVE: To describe reports of low-income Black non-Hispanic women about the
      promotion of infant-feeding methods by nurses and physicians. DESIGN:
      Ethnographic research conducted over 18 months with interviewing and participant
      observation of informants. SETTING: The study took place in a Special
      Supplemental Nutrition Program for Women, Infants, and Children clinic and
      neighborhood in the New York metropolitan area. PARTICIPANTS: 130 Black non
      Hispanic mothers enrolled in the Special Supplemental Nutrition Program for
      Women, Infants, and Children were general informants. From this group, 11
      primiparous key informants were selected for close follow-up during pregnancy and
      the 1st postpartum year. MAIN OUTCOME MEASURES: Audiotaped interviews and field
      notes were analyzed for mothers' descriptions of infant-feeding education and
      support from nurses and physicians. FINDINGS: The informants reported limited
      breastfeeding education and support during pregnancy, childbirth stay in neonatal
      intensive care unit, postpartum, and recovery in the community. They also
      expressed trust/distrust concerns and varying degrees of anxiety about the ways
      they were treated by nurses and physicians. CONCLUSIONS: To decrease disparities
      in breastfeeding, this research suggests that health care professionals should
      focus their efforts on the development of trusting relationships and continuity
      of care along with clear, consistent breastfeeding education and support.

PMID- 16620243
TI  - Nurse case management for pregnant women experiencing or at risk for abuse.
AB  - OBJECTIVE: To determine whether individualized nursing case management can
      decrease stress among pregnant women at risk for or in abusive relationships.
      DESIGN: A multisite randomized controlled trial. SETTING: Two prenatal clinics in
      the Pacific Northwest and rural Midwest. PARTICIPANTS: 1,000 women who spoke
      English and were 13 to 23 weeks pregnant at time of recruitment. INTERVENTION:
      All intervention group women (N = 499) were offered an abuse video and had access
      to a nurse case manager 24/7. Additionally, participants at risk for or in
      abusive relationships received individualized nursing care management throughout
      the pregnancy. RESULTS: The most frequent nursing care management activities were
      providing support (38%) and assessing needs (32%). The nursing care management
      group received an average of 22 contacts, most (80%) by telephone and had a
      significant reduction in stress scores as measured by the Prenatal Psychosocial
      Profile. Compared to the control group, the differences were in the predicted
      direction, but not statistically different. A major finding was the choice by
      abused women to focus on basic needs and their pregnancies rather than the abuse,
      although all received safety planning. CONCLUSIONS: Pregnant women at risk for or
      in abusive relationships experience very stressful and complex lives. Nurses need
      to focus on the needs they identify, which may not be the abusive relationship.

PMID- 16620244
TI  - Incidence of infection for preterm twins cared for in cobedding in the neonatal
      intensive-care unit.
AB  - OBJECTIVES: To describe the incidence of infection in a group of cobedded preterm
      twin infants and compare it to the incidence of infection in a cohort of preterm
      twin infants cared for in the same institution prior to the onset of cobedding.
      DESIGN: Retrospective descriptive design. SETTING: Tertiary, referral neonatal
      intensive-care unit in the Midwest. PARTICIPANTS: Preterm twin infants between 23
      and 35 weeks gestational age. METHODS: Data from 1997 to 2001 (cobedding)
      compared to data from 1992 to 1996 (no cobedding). MAIN OUTCOME MEASURE:
      Infection as evidenced by positive blood, cerebrospinal fluid, or urine culture
      or radiographic evidence of pneumonia or necrotizing enterocolitis. RESULTS:
      Independent samples t test found the cobedded and non-cobedded infants to be
      homogenous in demographic data. A 2-way analysis of variance demonstrated no
      significant effects for cobedded infants on number of sepsis evaluations or
      number of positive blood cultures. There was a statistically significant
      difference for number of positive blood cultures at discharge reflecting the
      increased number of positive blood cultures in the non-cobedded infants. Finally,
      there were no statistically significant differences found between cobedded and
      non-cobedded for the presence of pneumonia or necrotizing enterocolitis.
      CONCLUSIONS: Cobedding of preterm twins cared for in the intensive-care nursery
      was not associated with an increased incidence of infection. Prospective studies
      are needed on cobedding before a change in practice is implemented.

PMID- 16620246
TI  - Sociodemographic factors associated with weekend birth and increased risk of
      neonatal mortality.
AB  - OBJECTIVE: To learn whether weekend risk of neonatal mortality is related to
      selected sociodemographic factors. DESIGN: A retrospective cohort design.
      Logistic regression was used to obtain odds ratios, and analysis of variance and
      chi-square to identify differences in values and incidence of key variables.
      SAMPLES: The data were derived from matched Texas birth and infant death
      certificates from 1999 through 2001. MAIN OUTCOME MEASURES: A subset of deaths up
      to 28 days of life attributable to conditions originating in the perinatal
      period. These deaths were called neonatal mortality-p. RESULTS: Women who were
      White, married, had Medicaid assistance, and had private prenatal care were less
      likely to deliver on weekends. Odds of neonatal mortality-p increased 36.5% when
      a birth took place on the weekend. The weekend crude odds of neonatal mortality-p
      increased for all racial/ethnic groups, but the differences were not
      statistically significant. CONCLUSIONS: The likelihood of delivering on the
      weekend increases with certain sociodemographic factors. This fact is important
      because the risk of neonatal mortality is higher among weekend births.

PMID- 16620245
TI  - The effects of age and ethnicity on physical injury from rape.
AB  - OBJECTIVE: To determine whether postmenopausal (age 50 years or older) women
      would sustain significantly more injury after rape than women younger than 50 and
      to determine the role of skin pigmentation in the observance of genital injury.
      DESIGN AND SETTING: Registry data from a sexual assault forensic nurse examiners
      program. PARTICIPANTS: Based on date of examination, records from women of age 50
      years or older (n = 40) were matched to two other participants: a premenopausal
      group younger than 40 years and a perimenopausal group of 40 to 49 years. The
      final sample consisted of 120 subjects. MAIN OUTCOME MEASURES: Number, type, and
      location of injuries. RESULTS: A series of exact conditional logistic regression
      analyses indicated no significant association between age and genital,
      nongenital, or head injury. A significant association between race (Black versus
      White) and genital injury (adjusted odds ratio = 4.30, 95% confidence interval =
      1.09-25.98, p = .03) indicated that Whites were more than four times as likely as
      Blacks to have genital injury. CONCLUSION: Although the primary hypothesis was
      not supported, the role of racial/ethnic differences and their association with
      the observance of injury need further exploration to determine whether the
      standard forensic examination is appropriate for all women. Health disparities
      may exist if women of color are less likely than others to have genital injuries
      identified and treated. Alternatively, skin properties may explain racial/ethnic
      differences in injury prevalence.

PMID- 16620247
TI  - A model for postpartum smoking resumption prevention for women who stop smoking
      while pregnant.
AB  - Behavior change models and theories have been useful in our efforts to help
      people stop smoking. However, models that were developed for the general
      population do not always fit special populations such as pregnant women. Many
      women stop smoking while pregnant, but most resume smoking after giving birth. To
      help women who stop smoking while pregnant to stay smoke-free, a model for
      tailoring a smoking resumption-prevention intervention to the special needs of
      pregnant and postpartum women is proposed. The intervention begins during
      pregnancy, continues postpartum, and addresses pregnancy and parenting contextual
      factors in women's lives. The model is based on motivational theory and includes
      conducting patient assessments, developing risk profiles, triaging women to
      different levels of intervention intensity, and matching intervention strategies
      to women's risk profiles.

PMID- 16620249
TI  - Stages of change, processes of change, and social support for exercise and weight
      gain in postpartum women.
AB  - OBJECTIVES: To test the extent to which social support and variables included in
      the Transtheoretical Model were explanatory for exercise initiation and weight
      maintenance in postpartum women. DESIGN: A cross-sectional descriptive design.
      SETTING: Data were collected in the participant's homes. PARTICIPANTS: Postpartum
      women who had normal pregnancies were interviewed and measured on body fat,
      physical activity, and psychosocial scales. MAIN OUTCOME MEASURE: (a) Stages of
      exercise change measure, (b) Seven Day Recall, (c) Friend and Family Support for
      Exercise Scale, (d) Processes of Change Questionnaire, and (e) body fat measures
      including body mass index and percent body fat. RESULTS: Forty percent reported
      engaging in vigorous activity less than 1 hour daily, 55% walked less than four
      city blocks daily, and 52% engaged in less than 2 hours of vigorous weekend
      activity. Multilinear regression showed that the processes of change contributed
      36% to the body mass index, and 21% of the variance in waist-thigh ratio. Of the
      processes of change, environmental reevaluation correlated significantly with
      body mass index. CONCLUSION: The impact of a woman's weight on others as well as
      information concerning the health effects of obesity and physical activity could
      enhance the initiation of exercise in the postpartum woman.

PMID- 16620248
TI  - Breast and infant temperatures with twins during shared Kangaroo Care.
AB  - Kangaroo Care has been shown to keep a singleton preterm infant warm by body heat
      generated in maternal breasts that is conducted to the infant. No studies have
      examined whether twins simultaneously receiving Kangaroo Care, called Shared
      Kangaroo Care, are sufficiently warm and how the breasts respond to twin
      presence. Two case studies were done to determine the temperatures of twins being
      simultaneously kangarooed and the temperatures of maternal breasts during Shared
      Kangaroo Care. Two sets of premature twins were held in Shared Kangaroo Care for
      1.5 hours. Infant temperatures were recorded from incubators; breast temperatures
      were recorded from thermistors. Infant temperatures remained warm and increased
      during Kangaroo Care, and each breast appeared to respond to the thermal needs of
      the infant on that breast. Physiological explanations for thermal synchrony
      exist. These data suggest that twins can be simultaneously held in Kangaroo Care
      without thermal compromise because each breast responds individually to the
      infant's thermal needs.

PMID- 16620250
TI  - Directed attention in normal and high-risk pregnancy.
AB  - OBJECTIVE: To compare the ability to direct attention in women having a high-risk
      pregnancy with those having an uncomplicated pregnancy. DESIGN: Descriptive
      comparative. SETTING: A tertiary-care hospital. PARTICIPANTS: Women in the 3rd
      trimester of pregnancy receiving care from perinatologists were recruited for
      this study and comprised the high-risk group (n = 67). Women in their 3rd
      trimester of pregnancy with uncomplicated pregnancies and enrolled in prenatal
      classes were the comparison group (n = 57). MAIN OUTCOME MEASURES: Objective
      measures of directed attention included digit span forward, digit span backward,
      Trailmaking A, and Trailmaking B. Subjective measures included the Attentional
      Function Index and Mental Effort in Tasks. RESULTS: Women having a complicated
      pregnancy had significantly more difficulty directing attention on all measures
      than women having normal pregnancies. When all covariates were considered, women
      having a high-risk pregnancy had significantly more difficulty directing
      attention as measured by Trailmaking A, Trailmaking B, and Mental Effort in
      Tasks. CONCLUSIONS: Women having high-risk pregnancies may have more difficulty
      with activities that require directed attention than women having normal
      pregnancies. Learning new information and skills, problem solving, and planning
      may require additional effort for women having complicated pregnancies.

PMID- 16620251
TI  - A comparison of the postpartum learning needs of adolescent mothers and their
      mothers.
AB  - OBJECTIVES: To describe the postpartum learning needs of adolescent mothers and
      their mothers and to compare the differences between the learning needs of the 2
      groups of women. DESIGN: Descriptive cross-sectional survey design. SETTING: One
      university hospital and 2 private Midwestern hospitals. PARTICIPANTS: Convenience
      sample of 100 women (50 mother/daughter pairs). MAIN OUTCOME MEASURES: Postpartum
      teaching questionnaire-E, postpartum teaching questionnaire-F, and demographic
      questionnaire. RESULTS: There were no group differences between adolescent
      mothers and their mothers on baby-care items, but there were group differences on
      3 maternal-care items: emotional changes (p < .001), resumption of sexual
      activity (p < .001), and birth control (p = .009). CONCLUSIONS: Nurses may need
      to use different teaching strategies for adolescent mothers and their mothers
      about resumption of sexual activity, but the teaching strategies necessary for
      other postpartum topics may be similar. Further research is needed to determine
      where those similarities may be and to determine the most effective teaching
      strategies for each group of mothers.

PMID- 16620252
TI  - Actual versus instructed fasting times and associated discomforts in women having
      scheduled cesarean birth.
AB  - OBJECTIVES: To measure actual and instructed preoperative fasting durations in
      women undergoing scheduled cesarean birth, to compare these times with national
      guidelines for healthy patients undergoing elective procedures, and to describe
      discomforts associated with preoperative fasting. DESIGN: One group,
      nonexperimental, comparative, descriptive. SETTING: Nonprofit private medical
      center in Texas with 6,000 births/year. PATIENTS: Convenience sample of 51
      hospitalized postpartum women. INTERVENTIONS: Participants were interviewed an
      average of 44 hours after their cesarean birth, and their medical records were
      reviewed for fasting information. MAIN OUTCOME MEASURES: Duration of actual and
      instructed fasting, comparison with national guidelines, and ratings of thirst
      and hunger. RESULTS: The participants fasted from liquids and solids an average
      of 11 and 13 hours, respectively. Both actual and instructed fasting durations
      were significantly longer than national guidelines. Most participants (70%) were
      instructed to be nulla per os after midnight whether they were to have a.m. or
      p.m. surgery. Thirst and hunger scores averaged 5 and 4, respectively, on a 0-10
      scale. CONCLUSION: Patients having scheduled cesarean birth fast for
      unnecessarily long periods. Nurses should be knowledgeable about evidence-based
      preoperative fasting practices and collaborate with physicians to implement them.

PMID- 16620253
TI  - A pilot study of maternal and term infant outcomes associated with ultrathin
      nipple shield use.
AB  - OBJECTIVE: To examine maternal satisfaction with nipple shield use and maternal
      and infant physiological outcomes of breastfeeding with and without nipple
      shields. DESIGN: A descriptive study using a structured telephone survey to
      examine maternal satisfaction of nipple shield use and a within-subject design to
      compare maternal and infant physiological outcomes for a subset of mother-infant
      dyads. SETTING: Breastfeeding sessions were conducted in Pacific Northwest
      hospitals. PARTICIPANTS: 32 lactating women with experience using nipple shields;
      a subset of 5 maternal-infant dyads participated in the physiological part of the
      study. MAIN OUTCOME MEASURES: Maternal response to survey explored maternal
      satisfaction with nipple shield use. To examine maternal and infant physiological
      outcomes, two measures were used: infant test weighing to evaluate breast milk
      intake and maternal prolactin and cortisol levels to evaluate breast milk
      production. RESULTS: Maternal survey response indicated that use of nipple
      shields may prevent premature breastfeeding termination. Physiological results
      demonstrated no significant difference in maternal hormonal levels and infant
      breast milk intake for breastfeeding sessions with and without nipple shields.
      CONCLUSION: Use of nipple shields may be considered in face of potential
      abandonment of breastfeeding.

PMID- 16620256
TI  - Prenatal care: limitations and opportunities.
AB  - Prenatal care is a venerable tradition in the U.S. health care system and one
      that deserves critical examination. Inordinate amounts of public and personal
      resources are expended on a tradition of care that has not proven itself equal to
      current perinatal prevention challenges. In this article, the evolution of
      prenatal care is reviewed, its efficacy is critiqued, and efforts at
      restructuring the content and processes of care are examined. Three promising
      alternatives to the dominant medical model are described: the comprehensive
      prenatal care approach illustrated by many publicly funded prenatal clinics, the
      prenatal empowerment model as exemplified by midwifery care, and the prenatal
      group model as illustrated by CenteringPregnancy. Nurses are called upon to
      champion prenatal options for women.

PMID- 16620257
TI  - CenteringPregnancy group prenatal care: Promoting relationship-centered care.
AB  - CenteringPregnancy is an innovative model of group prenatal care that has been
      implemented at more than 100 prenatal care sites since 1995. CenteringPregnancy
      provides group prenatal care that is relationship centered, nurturing and
      transforming relationships among women, their families, and health care
      professionals. Complete prenatal care is provided in a group setting. Prenatal
      assessment, education, and support occur in a facilitative environment. The model
      offers effective and efficient care that is sustainable and can enhance the
      health of women, their families, health care providers, and communities.

PMID- 16620258
TI  - Birth plans: the good, the bad, and the future.
AB  - A written birth plan encourages women to clarify desires and expectations and
      communicate with their providers to make a realistic plan for care during labor.
      Tension between health professionals and patients caused by birth plans reflects
      the larger problems with contemporary maternity care: conflicting beliefs about
      birth, what constitutes safe, effective care, and ethical issues related to
      informed consent and informed refusal. The focus of birth plans should be to
      answer three patient-focused questions: What will I do to stay confident and feel
      safe? What will I do to find comfort in response to my contractions? Who will
      support me through labor, and what will I need from them? In this article, the
      history and purposes of birth plans and approaches to resolving tensions will be
      discussed.

PMID- 16620259
TI  - Nurses and doulas: complementary roles to provide optimal maternity care.
AB  - Staff in maternity-care facilities are seeing an increase in doulas, nonmedical
      childbirth assistants, who are trained to provide continuous physical, emotional,
      and informational labor support. The long-term medical and psychosocial benefits
      are well documented. In this article, misconceptions about the doula's role are
      corrected, and suggestions are offered on ways to improve communication between
      health care providers and doulas. Together, nurses and doulas can provide
      birthing women with a safe and satisfying birth.

PMID- 16620260
TI  - The evidence base to guide the use of antibiotics in foot ulcers in people with
      diabetes is thin, but what are we going to do about it?

PMID- 16620261
TI  - Systematic review of methods to diagnose infection in foot ulcers in diabetes.
AB  - AIM: To undertake a systematic review of the diagnostic performance of clinical
      examination, sample acquisition and sample analysis in infected foot ulcers in
      diabetes. METHODS: Nineteen electronic databases plus other sources were
      searched. To be included, studies had to fulfil the following criteria: (i)
      compare a method of clinical assessment, sample collection or sample analysis
      with a reference standard; (ii) recruit diabetic individuals with foot ulcers;
      (ii) present 2 x 2 diagnostic data. Studies were critically appraised using a 12
      item checklist. RESULTS: Three eligible studies were identified, one each on
      clinical examination, sample collection and sample analysis. For all three, study
      groups were heterogeneous with respect to wound type and a small proportion of
      participants had foot ulcers due to diabetes. No studies identified an optimum
      reference standard. Other methodological problems included non-blind
      interpretation of tests and the time lag between index and reference tests.
      Individual signs or symptoms of infection did not prove to be useful tests when
      assessed against punch biopsy as the reference standard. The wound swab did not
      perform well when assessed against tissue biopsy. Semiquantitative analysis of
      wound swab might be a useful alternative to quantitative analysis. The
      limitations of these findings and their impact on recommendations from relevant
      clinical guidelines are discussed. CONCLUSION: Given the importance of this
      topic, it is surprising that only three eligible studies were identified. It was
      not possible to describe the optimal methods of diagnosing infection in diabetic
      patients with foot ulceration from the evidence identified in this systematic
      review.

PMID- 16620262
TI  - Systematic review of antimicrobial treatments for diabetic foot ulcers.
AB  - BACKGROUND: Foot ulcers in diabetes are associated with increased mortality,
      illness and reduced quality of life. Ulcer infection impairs healing and
      antimicrobial interventions may cure infection, aid healing and reduce amputation
      rates. OBJECTIVES: To systematically review the evidence for antimicrobial
      interventions for foot ulcers in diabetes. METHODS: We searched 16 databases, 11
      Internet sites, three books, conference proceedings, a journal and bibliographies
      in November 2002. We included randomized controlled trials (RCTs) or controlled
      clinical trials (CCTs). RESULTS: Twenty-three studies investigated the
      effectiveness or cost-effectiveness of antimicrobial agents: intravenous
      antibiotics (n = 8); oral antibiotics (n = 5); topical antimicrobials (n = 4);
      subcutaneous granulocyte-colony stimulating factor (G-CSF) (n = 4); Ayurvedic
      preparations (n = 1): and sugar vs. antibiotics vs. standard care (n = 1). The
      trials were small and too dissimilar to be pooled. There is no strong evidence
      for any particular antimicrobial agent for the prevention of amputation,
      resolution of infection, or ulcer healing. Pexiganan cream may be as effective as
      oral ofloxacin for resolution of infection. Ampicillin and sulbactam cost less
      than imipenem/cilastatin, G-CSF cost less than standard care and cadexomer iodine
      dressings may cost less than daily dressings. CONCLUSIONS: The evidence is too
      weak to recommend any particular antimicrobial agent. Large studies are needed of
      the effectiveness and cost-effectiveness of antimicrobial interventions.

PMID- 16620263
TI  - Effect of hyperbaric oxygen on cardiac neural regulation in diabetic individuals
      with foot complications.
AB  - AIMS: There are relatively few effective methods to treat autonomic neuropathy in
      patients with diabetes mellitus. Our aim was to test the hypothesis that
      hyperbaric oxygen therapy may restore cardiac neural regulation dysfunction in
      diabetic individuals with foot complications. METHODS: We conducted a prospective
      randomized controlled study in patients with diabetic foot problems. Daily heart
      rate variability analysis from 5-min electrocardiography was used to evaluate the
      temporal change of cardiac neural regulation. The experimental group consisted of
      23 subjects exposed to hyperbaric oxygen therapy of 202.65 kPa for 90 min every
      Monday to Friday for 4 weeks (20 treatments). The control group consisted of 15
      age-, sex- and disease-matched subjects who were not exposed to hyperbaric
      therapy. Patients with medical complications and failure of wound healing were
      excluded to eliminate possible confounding effects. RESULTS: There was no
      significant difference in baseline R-R interval (RR), variance, high-frequency
      power (HF), low-frequency power (LF), and LF/HF ratio between the two groups. In
      the hyperbaric oxygen group there were significant increases in changes of RR
      (82.7 +/- 16.02 ms); variance 0.88 +/- 0.12 ln(ms2); HF 1.06 +/- 0.18 ln(ms2);
      and LF 0.87 +/- 0.15 ln(ms2) after the treatment. Measurements of tissue oxygen
      demonstrated significant increases in local tissue oxygenation in the hyperbaric
      oxygen group (53.0 +/- 2.6 mmHg) compared with the control group (27.5 +/- 3.1
      mmHg), P < 0.05. CONCLUSION: Hyperbaric oxygen therapy has a significant
      vagotonic effect, which is beneficial in improving cardiac neural regulation in
      patients with diabetic autonomic dysfunction.

PMID- 16620264
TI  - Variants in the gene encoding aldose reductase (AKR1B1) and diabetic nephropathy
      in American Indians.
AB  - AIMS: The aldose reductase gene (AKR1B1) is a strong candidate for diabetic
      nephropathy, and the T allele at rs759853 and the Z-2 allele at an [AC]n
      microsatellite are associated with diabetic kidney disease in some populations.
      As AKR1B1 is located on 7q35, where we have previously reported linkage to
      diabetic nephropathy in Pima Indians, this study examined the association of
      AKR1B1 variants with diabetic nephropathy in this population. METHODS: AKR1B1
      variants were identified by sequencing and genotyped using allelic discrimination
      and pyrosequencing. Genotype distributions were compared between 107 cases with
      diabetic end-stage renal disease and 108 control subjects with diabetes for > or
      = 10 years and no evidence of nephropathy, and between 141 individuals with
      nephropathy and 416 individuals without heavy proteinuria in a family study of
      257 sibships. RESULTS: We identified 11 AKR1B1 single nucleotide polymorphisms
      (SNPs) and the [AC]n microsatellite polymorphism. Three SNPs were rare and two
      were in 100% genotypic concordance; thus, eight polymorphisms were genotyped. No
      variant was associated with diabetic kidney disease in the case-control or family
      based study. For example, the T allele at rs759853 had an allele frequency of
      0.165 in cases and 0.171 in control subjects (OR = 0.96, 95% CI, 0.57-1.59, P =
      0.86); in the family study its frequency was 0.140 and 0.169 in affected and
      unaffected individuals, respectively (OR = 0.90, 95% CI, 0.53-1.54 P = 0.71).
      Corresponding values for the Z-2 allele at the [AC]n microsatellite were OR =
      1.09 (95% CI 0.72-1.66, P = 0.67) and OR = 1.25 (95% CI 0.81-1.95, P = 0.31) in
      the case-control and family studies, respectively. CONCLUSIONS: Common AKR1B1
      polymorphisms are unlikely to be major determinants of diabetic nephropathy in
      this population.

PMID- 16620265
TI  - The impact of second-level specialized care on hospitalization in persons with
      diabetes: a multilevel population-based study.
AB  - AIMS: We evaluated whether differences in the use of specialized care have an
      impact on rates of hospitalization for diabetes. METHODS: In 2001 we determined
      the number of hours of second-level diabetes care provided by local health units
      (LHU) of the Piemonte Region (Italy) and created an indicator of the mean weekly
      number of hours of care per 1000 residents for each LHU. From the database of the
      Piemonte Hospital Information System, we extracted all hospitalizations for 20-75
      year-old residents with a main discharge diagnosis of diabetes mellitus (n =
      3457). For each LHU, we calculated the hospitalization rate, the percentage of
      unplanned hospital admissions, the mean length of hospital stay, the percentage
      of day-hospital admissions and the percentage of re-admissions for diabetes
      related complications within 6 months. The association between the indicators of
      specialized care and of hospital care was studied using two-level generalized
      hierarchical linear regression models (level 1: patient; level 2: LHU), taking
      into account the clustered nature of the data. Age, educational level and an
      indicator of disease severity were used as adjustment parameters. RESULTS: In the
      tertile of LHUs that provided the greatest number of hours of diabetes care, we
      observed, compared with the lowest tertile fewer unplanned hospital admissions
      [odds ratio (OR) 0.37; 95% confidence interval (CI) 0.20-0.67], greater day
      hospital use (OR 1.99; 0.72-5.49) and a lower mean duration of hospital stay
      (coefficient -0.26; 95% CI -0.45 to -0.06), independently of the socio-economic
      level, which was a separate risk factor. CONCLUSIONS: The intensity of
      specialized diabetes care greatly influences the characteristics of
      hospitalization.

PMID- 16620266
TI  - A low-fat diet improves peripheral insulin sensitivity in patients with Type 1
      diabetes.
AB  - AIMS: To compare the effects on insulin sensitivity, body composition and
      glycaemic control of the recommended standard weight-maintaining diabetes diet
      and an isocaloric low-fat diabetes diet during two, 3-month periods in patients
      with Type 1 diabetes. METHODS: Thirteen Type 1 patients were included, of whom 10
      completed the cross-over study. Ten non-diabetic, matched control subjects were
      also examined. Body composition was estimated by dual-energy X-ray absorptiometry
      (DXA) whole-body scanning, diet intake was monitored by 7-day dietary record and
      insulin sensitivity was measured by the insulin clamp technique at baseline and
      after each of the diet intervention periods. RESULTS: On an isocaloric low-fat
      diet, Type 1 diabetic patients significantly reduced the proportion of fat in the
      total daily energy intake by 12.1% (or -3.6% of total energy) as compared with a
      conventional diabetes diet (P = 0.039). The daily protein and carbohydrate intake
      increased (+4.4% of total energy intake, P = 0.0049 and +2.5%, P = 0.34,
      respectively), while alcohol intake decreased (-3.2% of total energy intake, P =
      0.02). There was a significant improvement in insulin sensitivity on the
      isocaloric, low-fat diet compared with the standard diabetes diet [7.06 +/- 2.16
      mg/kg/min (mean +/- sd) vs. 5.52 +/- 2.35 mg/kg/min (P = 0.03)]. However, insulin
      sensitivity remained 33% lower than in the control subjects (P = 0.021). No
      significant changes occurred in body weight or body composition. Glycated
      haemoglobin rose during both diet intervention periods (P = 0.18), with no
      difference between the two diets. CONCLUSIONS: Change to an isocaloric, low-fat
      diet in Type 1 diabetic patients during a 3-month period resulted in significant
      improvement in insulin sensitivity without improvement in glycaemic control.
      However, insulin sensitivity remained 33% lower than in control subjects.

PMID- 16620267
TI  - Diabetes and risk of acute infectious conjunctivitis--a population-based case
      control study.
AB  - AIMS: To examine whether diabetes mellitus is associated with an increased risk
      of acute infectious conjunctivitis (AIC) in adults, as measured by treatment with
      topical ocular antibiotics. METHODS: A population-based, case-control study in
      North Jutland County, Denmark. Incident cases of AIC were defined as persons aged
      more than 15 years redeeming a first-time prescription for a topical ocular
      antibiotic during 1999 in the County Prescription Database. Five gender- and age
      matched population control subjects per case were selected using a unique
      personal identifier, the Civil Registry Number. Diabetes prior to the ocular
      antibiotic prescription was determined by record-linkage with the Prescription
      Database and Hospital Discharge Registry in the county. Odds ratios (ORs) for
      acute infectious conjunctivitis among diabetic individuals and control subjects
      were estimated, adjusting for a range of potential risk factors. RESULTS: Among
      16 193 adults treated with topical ocular antibiotics, 3.1% had diabetes as
      compared with 2.5% of the control subjects. The overall adjusted OR for acute
      infectious conjunctivitis in patients with diabetes was 1.24 [95% confidence
      interval (CI): 1.13-1.38]. Risk estimates of acute infectious conjunctivitis in
      individuals with diabetes were consistently increased for both women and men, for
      all age groups, and for different types of ocular antibiotics prescribed.
      CONCLUSIONS: This study suggests that diabetes is a risk factor for acute
      infectious conjunctivitis.

PMID- 16620268
TI  - Blunted response to systemic nitric oxide synthase inhibition in the cerebral
      circulation of patients with Type 2 diabetes.
AB  - AIMS: Diabetes is a major risk factor for stroke, but the mechanisms that impart
      the excess risk are unclear. Endothelial dysfunction, which has been demonstrated
      in the coronary and peripheral vasculature of diabetic patients, is an important
      early marker of vascular disease. However, the effect of diabetes on
      cerebrovascular endothelium has not been examined. We sought to investigate the
      effect of diabetes on basal cerebrovascular endothelial function as assessed by
      response to the nitric oxide synthase (NOS) inhibitor NG-monomethyl-L-arginine (L
      NMMA). METHODS: Fourteen men with Type 2 diabetes and 15 age-matched male control
      subjects were recruited. The participants had no clinically evident vascular
      disease and were taking no vasoactive or lipid-lowering medication. Each received
      a single 15-min intravenous infusion of L-NMMA (0.8 mol/kg/min). Cerebral blood
      flow was assessed by colour Doppler imaging of the internal carotid artery (ICA)
      at 10-min intervals for 20 min prior to and following the infusion. Middle
      cerebral artery velocity (MCAv) was assessed by transtemporal Doppler ultrasound
      at the same time points. RESULTS: L-NMMA produced a mean reduction in ICA flow
      area under curve (AUC) in the control group of 12.8 +/- 17.8% compared with a 2.1
      +/- 21.7% reduction in the group with diabetes (P < 0.05), indicating blunted
      basal cerebrovascular response to NOS inhibition in the diabetic group. There was
      no significant change in MCAv following L-NMMA in either group. Mean +/- sd MAP
      rose 6.4 +/- 4.2 mmHg in the control group vs. 8.8 +/- 3.5 mmHg in the diabetic
      group [P = not significant (NS)]. No adverse event or symptom was reported.
      CONCLUSIONS: Response to NOS inhibition is impaired in the cerebral circulation
      of patients with diabetes. This observation is consistent with the elevated
      cerebrovascular risk reported in this population, and may represent a future
      therapeutic target in stroke prevention.

PMID- 16620269
TI  - Increased prevalence of cardiovascular disease in Type 2 diabetic patients with
      non-alcoholic fatty liver disease.
AB  - AIMS: To estimate the prevalence of cardiovascular disease (CVD) in Type 2
      diabetic patients with and without non-alcoholic fatty liver disease (NAFLD), and
      to assess whether NAFLD is independently related to prevalent CVD. METHODS: We
      studied 400 Type 2 diabetic patients with NAFLD and 400 diabetic patients without
      NAFLD who were matched for age and sex. Main outcome measures were prevalent CVD
      (as ascertained by medical history, physical examination, electrocardiogram and
      echo-Doppler scanning of carotid and lower limb arteries), NAFLD (by
      ultrasonography) and presence of the metabolic syndrome (MetS) as defined by the
      World Health Organization or Adult Treatment Panel III criteria. RESULTS: The
      prevalences of coronary (23.0 vs. 15.5%), cerebrovascular (17.2 vs. 10.2%) and
      peripheral (12.8 vs. 7.0%) vascular disease were significantly increased in those
      with NAFLD as compared with those without NAFLD (P < 0.001), with no differences
      between sexes. The MetS (by any criteria) and all its individual components were
      more frequent in NAFLD patients (P < 0.001). In logistic regression analysis,
      male sex, age, smoking history and MetS were independently related to prevalent
      CVD, whereas NAFLD was not. CONCLUSIONS: The prevalence of CVD is increased in
      patients with Type 2 diabetes and NAFLD in association with an increased
      prevalence of MetS as compared with diabetic patients without NAFLD. Follow-up
      studies are necessary to determine whether this higher prevalence of CVD among
      diabetic patients with NAFLD affects long-term mortality.

PMID- 16620270
TI  - Myocardial perfusion imaging and cardiac events in a cohort of asymptomatic
      patients with diabetes living in southern France.
AB  - AIMS: To assess the association between abnormal stress myocardial perfusion
      imaging (MPI) and cardiac events (CE) in asymptomatic patients with diabetes and
      with > or = 1 additional risk factor. Predictors of abnormal stress MPI were also
      evaluated. METHODS: Four hundred and forty-seven consecutive patients who
      underwent stress MPI were prospectively followed for 2.1 [0.5-4.1] years for the
      subsequent occurrence of hard CE (myocardial infarction and sudden or coronary
      death) and soft CE (unstable angina and ischaemic heart failure requiring
      hospitalization). Re-vascularization procedures performed as a result of the
      screening protocol were not included in the analysis. RESULTS: Follow-up was
      successful in 419 of 447 patients (94%), of whom 71 had abnormal MPI at baseline.
      Medical therapy was intensified in all subjects and especially in those with
      abnormal MPI. Twenty-three patients with abnormal MPI underwent a re
      vascularization procedure. CEs occurred in 14 patients, including six of 71
      patients (8.5%) with abnormal MPI and eight of 348 patients (2.3%) with normal
      MPI (P < 0.005). Only two patients developed a hard CE and 12 a soft CE. In
      multivariate analysis, abnormal MPI was the strongest predictor for CEs [odds
      ratio (OR) (95% CI) = 5.6 (1.7-18.5)]. Low-density lipoprotein cholesterol > or =
      3.35 mmol/l [OR (95% CI) = 7.3; 1.5-34.7] and age > median [OR (95% CI) = 6.0
      (1.2-28.6)] were additional independent predictors for CE. The independent
      predictors for abnormal MPI were male gender, plasma triglycerides > or = 1.70
      mmol/l, creatinine clearance < 60 ml/min and HbA1c > 8%, with male gender the
      strongest [OR (95% CI) = 4.0 (1.8-8.8)]. CONCLUSIONS: Asymptomatic patients with
      diabetes in this study had a very low hard cardiac event rate over an
      intermediate period. This could be explained by the effects of intervention or by
      the low event rate in the background population. Randomized studies of cardiac
      heart disease screening are required in asymptomatic subjects with diabetes to
      determine the effectiveness of this intervention.

PMID- 16620271
TI  - Association of the promoter polymorphism -232C/G of the phosphoenolpyruvate
      carboxykinase gene (PCK1) with Type 2 diabetes mellitus.
AB  - AIMS: The phosphoenolpyruvate carboxykinase gene (PCK1) is a potential candidate
      gene in the pathogenesis of Type 2 diabetes mellitus. A -232C/G promoter
      polymorphism of PCK1 has been associated with an increased risk of Type 2
      diabetes in a Canadian population. The purpose of the present study was to
      examine this association in a German Caucasian population. METHODS: We
      investigated 397 subjects with Type 2 diabetes [227 men, 170 women, age 63 +/- 11
      years, body mass index (BMI) 28.7 +/- 5.1 kg/m2] and 431 control subjects without
      diabetes (247 men, 184 women, age 64 +/- 7 years, BMI 26.5 +/- 3.7 kg/m2) matched
      for sex and age. RESULTS: In the diabetic and control groups, the CC genotype
      frequencies were 18.1 and 18.3%, the CG 48.6 and 48.7% and the GG 33.2 and 32.9%,
      respectively (P = 0.995). The allelic frequencies were 0.51 and 0.57 for the G
      allele and 0.49 and 0.43 for the C allele, respectively. In a logistic regression
      model only BMI and family history, but not the polymorphism, were predictors of
      Type 2 diabetes. In both the control and diabetic subjects, there were no
      significant differences in BMI or blood pressure between the groups with or
      without the polymorphism. The variant also had no significant influence on the
      presence of atherosclerotic disease, while the influence of other known
      cardiovascular risk factors was confirmed. CONCLUSIONS: The present data suggest
      that, in a German Caucasian population, the -232C/G polymorphism of the PEPCK
      gene is not associated with Type 2 diabetes.

PMID- 16620272
TI  - Reduced prevalence of early preterm delivery in women with Type 1 diabetes and
      microalbuminuria--possible effect of early antihypertensive treatment during
      pregnancy.
AB  - AIMS: In normotensive women with Type 1 diabetes and microalbuminuria we
      previously found preterm delivery (< 34 weeks) in 23% of the pregnancies.
      Antihypertensive treatment was initiated in late pregnancy when preeclampsia was
      diagnosed and diastolic blood pressure > 90 mmHg. From April 2000 our routine was
      changed and early antihypertensive treatment with methyldopa was initiated if
      antihypertensive treatment was given prior to pregnancy, if urinary albumin
      excretion (UAE) was > 2 g/24 h, or blood pressure > 140/90 mmHg. The present
      study describes the impact of this more aggressive antiypertensive treatment in
      the prevalence of preterm delivery. METHODS: The old cohort (1995-1999) consisted
      of 26 and the new cohort (2000-2003) of 20 pregnant women with Type 1 diabetes
      and microalbuminuria. All were referred before gestational week 17. RESULTS: The
      cohorts were comparable with regard to age, diabetes duration, prepregnancy body
      mass index, HbA1c, blood pressure 121 (13)/71 (8) vs. 121 (14)/73 (8) mmHg [mean
      (sd)] and early UAE 69 (16-278) vs. 74 (30-287) mg/24 h (geometric mean and
      range). Antihypertensive treatment was initiated in the old cohort at 29 (20-33)
      weeks, n = 9, and in the new at 13 (0-34) weeks, n = 10. The prevalence of
      preterm delivery before 34 weeks was reduced from 23% to zero (P = 0.02), preterm
      delivery before 37 weeks from 62% to 40% (P = 0.15) and preeclampsia from 42% to
      20% (P = 0.11). Perinatal mortality occurred in 4% vs. 0%. Birth weight was 3124
      (767) g vs. 3279 (663) g. CONCLUSION: Introduction of early antihypertensive
      treatment with methyldopa in normotensive pregnant women with Type 1 diabetes and
      microalbuminuria resulted in a significant reduction in preterm delivery before
      gestational week 34.

PMID- 16620273
TI  - Severe acidosis in patients taking metformin--rapid reversal and survival despite
      high APACHE score.
AB  - BACKGROUND: Metformin has been shown to reduce complications and mortality from
      Type 2 diabetes mellitus, and is increasingly used to treat this condition. This
      agent is, however, associated with a rare but serious risk of lactic acidosis.
      CASE REPORT: We present cases of 10 patients with Type 2 diabetes mellitus who
      developed acute renal failure and severe lactic acidosis. Despite the severity of
      their illness, all patients but one survived. CONCLUSIONS: The increasing
      prevalence of Type 2 diabetes and its treatment with metformin might result in
      more cases of lactic acidosis. However our case report demonstrates that early
      and aggressive treatment with haemofiltration can improve outcomes even in the
      presence of severe acidosis.

PMID- 16620274
TI  - Diabetes with partial lipodystrophy following sclerodermatous chronic graft vs.
      host disease.
AB  - BACKGROUND: The importance of adipose tissue in metabolism, as a target for
      insulin action and a secretor of metabolic regulatory proteins, is increasingly
      recognized. Lipodystrophic conditions are often associated with significant
      insulin resistance. The commonest acquired form occurs with highly active
      antiretroviral therapy (HAART) for human immunodeficiency virus infection. Other
      medical conditions and drugs also have the potential to cause chronic
      subcutaneous fat damage. CASE REPORT: We describe an unfamiliar partial
      lipodystrophy in a young woman, associated with markedly insulin-resistant
      diabetes, acquired following allogeneic bone marrow transplantation for childhood
      leukaemia complicated by late sclerodermatous chronic graft vs. host disease
      (GVHD). Clinical examination revealed scarring and lipodystrophy affecting mainly
      legs, thighs, buttocks and forearms but sparing her face, neck and thorax. Her
      serum adiponectin level was markedly reduced. CONCLUSIONS: However, although
      thiazolidinediones lower insulin resistance and increase subcutaneous peripheral
      fat in Type 2 diabetes, pioglitazone treatment had little effect on either serum
      adiponectin, glycaemic control or the lipoatrophy. In this case, effective
      glycaemic control was best achieved using a combination of metformin and highly
      concentrated soluble insulin injections.

PMID- 16620275
TI  - The metabolic syndrome in an Arab population: a first look at the new
      International Diabetes Federation criteria.
AB  - AIMS: To report the prevalence of the metabolic syndrome in Arab men and women
      using the new International Diabetes Federation (IDF) criteria, and to compare
      this with the prevalence using the 1999 World Health Organization (WHO) and 2001
      National Cholesterol Education Program Adult Treatment Panel III (NECP ATPIII)
      definitions. METHODS: The study involved 863 subjects (343 men and 520 women)
      aged > or = 40 years living in Tunis, Tunisia, taken from an initially
      randomized, population sample. RESULTS: The prevalence of the metabolic syndrome
      using the IDF criteria was found to be 45.5%; 55.8% in women and 30.0% in men (P
      < 0.001), higher than the rates of 28.7% (WHO) and 24.3% (NECP ATPIII) using the
      previous definitions. Using all the definitions, the prevalence was higher in
      women than in men predominantly because of significant differences in central
      obesity and high-density lipoprotein (HDL) cholesterol and, to a lesser extent,
      hypertension. CONCLUSION: The increased prevalence using the IDF criteria
      compared with the 1999 WHO criteria and the 2001 NCEP ATPIII definitions is
      striking and has huge implications for public health worldwide. The major reason
      for the higher rate using the new definition seems to be the predominant focus
      placed on central obesity. Using tighter criteria for fasting glycaemia has also
      played a factor. The question remains as yet unanswered as to whether the new IDF
      criteria are better at predicting hard outcomes such as diabetes mellitus and
      cardiovascular diseases.

PMID- 16620276
TI  - The prevalence of co-morbid depression in adults with Type 1 diabetes: systematic
      literature review.
AB  - AIM: To review the literature estimating the cross-sectional prevalence of
      clinical depression in adults with Type 1 diabetes. METHODS: Electronic databases
      and published references were used to identify studies published between January
      2000 and June 2004, with a previous meta-analysis used to identify studies before
      1 January 2000. RESULTS: Between January 2000 and June 2004, a further five
      eligible studies were identified. Only one was a controlled study using
      diagnostic interviewing to determine rates of depression. Taking all of the
      eligible studies identified by the previous meta-analysis and this search, the
      prevalence of clinical depression in controlled studies was 12.0% for people with
      diabetes compared with 3.2% for control subjects. In studies with no control
      group, the prevalence of clinical depression was 13.4%. CONCLUSION: There are
      wide-ranging differences reported in the various studies on the prevalence of
      depression in Type 1 diabetes. In view of the differing methods of diagnosis and
      small participant numbers, the results should be viewed with caution. A
      controlled study using diagnostic interviewing techniques to determine levels of
      depression is recommended to provide a clearer picture of both the prevalence and
      characteristics of that depression.

PMID- 16620278
TI  - Diabetic retinopathy screening programmes and reducing ophthalmologists'
      workload.

PMID- 16620280
TI  - Type 2 diabetes in rural and urban population: diverse prevalence and associated
      risk factors in Bangladesh.

PMID- 16620281
TI  - Markers of eosinophilic inflammation and risk prediction in patients with
      coronary artery disease.
AB  - BACKGROUND: The eotaxin family comprises three distinct peptides (eotaxin,
      eotaxin-2 and eotaxin-3) which have been implicated in eosinophilic inflammation.
      In vitro and clinical studies suggest that eotaxins could play a role in vascular
      inflammation, but no data are available on their prognostic significance in
      patients with angiographically documented coronary artery disease (CAD).
      MATERIALS AND METHODS: Baseline plasma samples were obtained from 1014 patients
      with documented CAD. We tested the predictive effect of markers of eosinophilic
      inflammation and C-reactive protein (CRP) on death from cardiovascular causes and
      nonfatal myocardial infarction over a 2.7-4.1-year follow-up period. RESULTS:
      Unexpectedly, lower eotaxin-3 concentrations were observed in patients with
      adverse cardiovascular events, whereas both eotaxin and eotaxin-2 showed no
      association with risk. After adjustment for most potential confounders, patients
      in the upper-quartile of eotaxin-3 levels had a 0.42 hazard-ratio (95% CI, 0.29
      0.61, P < 0.001) for adverse events compared with subjects in the lower-quartile.
      The highest risk of future cardiovascular events was observed in subjects with
      combined elevation of CRP and reduction of eotaxin-3; 4.4 hazard-ratio (95% CI,
      2.1-9.5, P < 0.001). Importantly, receiver-operating-characteristic curves
      analysis suggested a superior prognostic value of eotaxin-3 compared with CRP for
      predicting cardiac events in patients with CAD. CONCLUSIONS: Low levels of
      eotaxin-3 are an independent predictor of future adverse cardiovascular events in
      patients with CAD and may be useful for risk stratification.

PMID- 16620282
TI  - Increased coronary sinus blood temperature: correlation with systemic
      inflammation.
AB  - BACKGROUND: Recent studies have shown that patients with single vessel coronary
      artery disease (CAD) suffering from acute coronary syndromes (ACS) have increased
      coronary sinus (CS) blood temperature compared with the right atrium (RA). The
      aim of this study was to investigate whether there is a correlation between
      systemic inflammatory indexes and CS temperature and whether there is a
      difference in CS temperature between patients with single vs. multivessel
      disease. MATERIALS AND METHODS We included consecutive patients scheduled for
      coronary angiography for recent-onset chest pain evaluation. We measured C
      reactive protein (CRP) levels in the study population. Coronary sinus and RA
      blood temperature measurements were performed by a 7F thermography catheter.
      DeltaTau was calculated by subtracting the RA from the CS blood temperature.
      RESULTS: The study population comprised 53 patients with ACS, 25 patients with
      stable angina (SA) and 22 subjects without CAD (control group). DeltaTau was
      greater in patients with ACS and with SA compared with the control group (0.22 +/
      0.10 degrees C, 0.18 +/- 0.04 degrees C vs. 0.14 +/- 0.07 degrees C, P < 0.01
      for both comparisons). The ACS group had greater DeltaTau compared with the SA
      group, although the difference did not reach statistical significance (P = 0.09).
      Eighteen (39.1%) out of 46 patients with multivessel disease had three-vessel
      disease and 28 (60.8%) had two-vessel disease. DeltaTau between patients with
      multivessel and single vessel disease was similar (0.22 +/- 0.01 degrees C, 0.19
      +/- 0.01 degrees C, P = 0.17). The levels of CRP were well correlated with
      DeltaTau (R = 0.35b, P < 0.01). CONCLUSIONS: Systemic inflammation is well
      correlated with CS temperature; thus, an inflammatory process could be the
      underlying mechanism for increased heat production from the myocardium.

PMID- 16620283
TI  - Effects of atorvastatin on high-density lipoprotein apolipoprotein A-I metabolism
      in dogs.
AB  - BACKGROUND: The mechanisms involved in the decline of high-density lipoprotein
      (HDL) levels at a higher dose of atorvastatin have not yet been elucidated. We
      investigated the effects of atorvastatin on HDL-apolipoprotein (apo) A-I
      metabolism in dogs, a species lacking cholesteryl ester transfer protein
      activity. MATERIALS AND METHODS: Seven ovariectomized normolipidaemic female
      Beagle dogs underwent a primed constant infusion of [5,5,5-(2)H(3)] leucine to
      determine HDL-apo A-I kinetics before and after atorvastatin treatment (5 mg kg(
      1) d(-1) for 6 weeks). Plasma lipoprotein profiles, activity of HDL-modifying
      enzymes involved in reverse cholesterol transport and hepatic scavenger receptor
      class B type I (SR-BI) expression were also studied. RESULTS: Atorvastatin
      treatment decreased HDL-cholesterol levels (3.56 +/- 0.24 vs. 2.64 +/- 0.15 mmol
      L(-1), P < 0.05). HDL-triglycerides were not affected. HDL-phospholipids levels
      were decreased (4.28 +/- 0.13 vs. 3.29 +/- 0.13 mmol L(-1), P < 0.05), as well as
      phospholipids transfer protein (PLTP) activity (0.83 +/- 0.05 vs. 0.60 +/- 0.05
      pmol microL(-1) min(-1), P < 0.05). Activity of lecithin: cholesterol acyl
      transferase (LCAT), hepatic lipase (HL) and SR-BI expression did not change. HDL
      apo A-I absolute production rate (APR) was higher after treatment (twofold, P <
      0.05) as well as fractional catabolic rate (FCR) (threefold, P < 0.05). This
      resulted in lower HDL-apo A-I levels (2.36 +/- 0.03 vs. 1.55 +/- 0.04 g l(-1), P
      < 0.05). Plasma lipoprotein profiles showed a decrease in large HDL(1) levels,
      with lower apo A-I and higher apo E levels in this subfraction. CONCLUSIONS:
      Although a high dose of atorvastatin up-regulated HDL-apo A-I production, this
      drug also increased HDL-apo A-I FCR in dogs. This effect could be explained by a
      higher uptake of apo E-enriched HDL(1) by hepatic lipoprotein receptors.

PMID- 16620284
TI  - Insulin secretion and sensitivity as determinants of HbA1c in type 2 diabetes.
AB  - BACKGROUND: Defects in insulin secretion and sensitivity, two major determinants
      of glycaemic control, can occur and progress or not in parallel. The present
      study was designed to compare the respective roles of both determinants on HbA1c,
      in type 2 diabetic patients, according to whether or not residual beta-cell
      function was stimulated with insulin secretagogues. MATERIALS AND METHODS:
      Insulin secretion and insulin sensitivity were both estimated using the
      homeostasis model assessment (HOMA). HbA1c, insulin sensitivity (HOMA2%S) and
      insulin secretion (HOMA2%B) were determined in 289 noninsulin-using type 2
      diabetic patients who were further divided into two groups according to
      treatment: metformin alone (group I, n = 57) or metformin and glyburide (group
      II, n = 232). The patients of both groups were further divided into three subsets
      in order to test the dependence of HbA1c on HOMA2%B and HOMA2%S. RESULTS: In
      group I mean HbA1c were greater (8.4%) in patients with HOMA2%B < 50% than in the
      two subsets with HOMA2%B > or = 50%: 7.2 and 6.8% (P = 0.0013). In group II mean
      values of stimulated-insulin secretion (HOMA2%B) were lesser (40.7 and 30.1%) in
      the two subsets of patients with HbA1c > or = 8% than in patients with HbA1c <
      8%: 55.1% (P < 0.0001). By contrast, we found no differences in both groups with
      HOMA2%S. A stepwise multiple regression showed that HOMA2%B contributed to HbA1c
      more than HOMA2%S both in groups I (33.5% vs. 23.4%) and II (22.7% vs. 8%).
      CONCLUSIONS: Although the role of insulin sensitivity is not negligible, insulin
      secretion appears to be the major determinant of diabetic control in overt type 2
      diabetic patients who are treated with metformin alone or with a two-drug therapy
      combining metformin and glyburide.

PMID- 16620285
TI  - Interaction between cigarette, alcohol and betel nut use on esophageal cancer
      risk in Taiwan.
AB  - OBJECTIVE: In 2003 esophageal cancer was the sixth leading cause of death among
      men in Taiwan, but it is the fastest increasing (70%) alimentary tract cancer.
      The aim of this study was to investigate the impact of different habits of betel
      nut chewing on esophageal squamous cell carcinoma (SCC) and its interaction with
      cigarette use and alcohol consumption. MATERIALS AND METHODS: All 165 cases were
      pathologically proven esophageal SCC patients (all male, mean age = 56.0, range =
      35-92 years) diagnosed by biopsy during gastroendoscopic examinations. The
      control group comprised 255 subjects (all male, mean age = 54.8, range = 40-92
      years) selected from patients who had visited the Otolaryngology Outpatient or
      Inpatient Department of KMUH owing to a benign lesion over this field. All were
      interviewed to collect demographic and substance use information by a trained
      interviewer using a standardized questionnaire. RESULTS: Smoking (aOR = 5.4, 95%
      CI = 2.4-12.9, PAR = 72%), alcoholic beverage drinking (aOR = 17.6, 95% CI = 9.3
      35.2, PAR = 76%) and low education level are independent risk factors for
      esophageal cancer. Although betel nut chewers only had a borderline significant
      higher risk than nonchewers (aOR = 1.7; 95% CI = 0.8-3.1), those who chewed with
      a piece of betel inflorescence (aOR = 4.2, 95% CI = 1.4-16.0) and swallow betel
      quid juice (aOR = 3.3, 95% CI = 1.3-9.3) had a significant higher risk.
      Significant dose-response effects were found in daily quantity of drinking and
      smoking. There is a synergistic effect of these three substances on the
      development of esophageal cancer. CONCLUSION: Betel nut chewing plays a relevant
      role in the development of esophageal SCC but adds to the carcinogenetic effect
      of smoking and alcohol drinking. Direct mucosal contact of betel juice may
      contribute to its carcinogenesis.

PMID- 16620286
TI  - A stable model of cirrhotic portal hypertension in the rat: thioacetamide
      revisited.
AB  - BACKGROUND: Cirrhotic animal models are vital to investigate complications of
      chronic liver disease. We chronologically characterized the effect of
      thioacetamide, administrated orally and adapted weekly to weight changes,
      focusing on the optimal moment to obtain all typical features of portal
      hypertension and cirrhosis. MATERIALS AND METHODS: Male Wistar rats, 200-250 g,
      were intoxicated for 6, 12 or 18 weeks (n = 8 per group), respectively, and
      compared with age-matched controls (n = 4 per group). An in-situ perfusion model
      was used to evaluate intrahepatic resistance and endothelial function. Splanchnic
      blood flow and portosystemic shunting were assessed by a perivascular flow probe.
      RESULTS: Rats intoxicated for 6 or 12 weeks had no mortality and histologically
      showed hepatitis and advanced fibrosis, respectively. At 18 weeks, mortality was
      16% (on a total of 56 animals) and only at that moment all animals showed
      homogenous macronodular cirrhosis with signs of high-grade hepatocellular
      dysplasia. Portal hypertension was present at 12 weeks (11 +/- 0.4 vs. 5.9 +/-
      0.4 mmHg, P < 0.001), but was not associated with the hyperdynamic state until 18
      weeks (12.1 +/- 0.8 vs. 5.6 +/- 0.5 mmHg, P < 0.001). At this latter time-point,
      we also observed increased intrahepatic resistance associated with endothelial
      dysfunction, hyperresponsiveness to vasoconstrictors, splanchnic hyperaemia and
      portosystemic shunting. These alterations were associated with increased systemic
      levels of nitrate/nitrite and thromboxane A(2). CONCLUSION: Thioacetamide,
      adapted to weekly weight changes, leads to a homogenous, reproducible model of
      cirrhosis in the rat in 18 weeks, which is associated with all the typical
      characteristics of portal hypertension, including endothelial dysfunction.

PMID- 16620287
TI  - T-lymphocyte subset distribution in human spleen.
AB  - BACKGROUND: When analyzing human cellular immune responses, most focus is placed
      on the peripheral blood (PB) and, to a lesser extent, the lymph nodes. To date
      the spleen has not been analyzed with regard to its role in adaptive cellular
      immunity and more notably not with respect to T-cell immune responses. MATERIALS
      AND METHODS: We analyzed the splenic lymphocyte compartment in comparison with
      the PB lymphocyte compartment regarding the number of NK cells, B cells, CD4(+),
      CD8(+) T cells and CMV-specific CD8(+) T cells. Furthermore, we analyzed the
      distribution of naive, memory and effector subsets of CD4(+) and CD8(+) T cells
      in these compartments. RESULTS: The spleen contains proportionally more B cells
      and less CD4(+) and CD8(+) T cells than PB. The percentage of CD8(+) T cells is
      greater in the spleen, leading to an inverse CD4/CD8 ratio. Both splenic CD4(+)
      and CD8(+) T-cell populations show a greater number of activated cells, and
      splenic CD8(+) T cells show a more differentiated cytotoxic CD27(-)CD45RA(+)
      memory phenotype. CONCLUSIONS: Our findings show that the distribution of the
      different lymphocyte subsets is markedly different between the spleen and the PB,
      thus inferring an important and distinct role for the spleen in CD4(+) and CD8(+)
      T-cell activation.

PMID- 16620288
TI  - Skewing of X-chromosome inactivation in three generations of carriers with X
      linked chronic granulomatous disease within one family.
AB  - BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of the
      innate immune system characterized by impairment of intracellular microbicidal
      activity of phagocytes. Mutations in one of the four known NADPH-oxidase
      components preclude generation of superoxide and related antimicrobial oxidants,
      leading to the phenotype of CGD. Defects in gp91-phox, encoded by CYBB, lead to X
      linked CGD, responsible for approximately 70% of all CGD cases. The aim of the
      study was to evaluate the hypothesis that age-related skewing of X-chromosome
      inactivation, as described in several CGD families, is caused by preferential
      survival of bone marrow clones with an inactive NADPH oxidase. MATERIALS AND
      METHODS: We studied the neutrophils from three patients and four carriers in
      three generations of a Turkish family with X-linked CGD. Carrier detection was
      carried out by the dihydrorhodamine (DHR)-1,2,3 assay, which measures on a per
      cell basis the NADPH oxidase-dependent oxidation of DHR by phagocytes. The X
      chromosome inactivation pattern was determined with the HUMARA assay in DNA from
      leucocytes as well as in DNA from a buccal smear of the four carriers. RESULTS:
      The three patients were identified by a negative DHR test, and the mutation in
      their CYBB gene was characterized by DNA sequencing. Moreover, we found an age
      related degree of skewing of X-chromosome inactivation in the leucocytes of the
      four X-CGD carriers, both at the protein level (NADPH oxidase activity) and at
      the DNA level (HUMARA assay). However, similar skewing of X-chromosome
      inactivation was found in the buccal DNA from these women. CONCLUSIONS: These
      novel findings indicate that the age-related degree of skewing was probably a
      chance finding, not related to preferential survival of NADPH oxidase-deficient
      precursor cells, because this enzyme is not expressed in (buccal) epithelial
      cells.

PMID- 16620290
TI  - Acute systemic complications in the preterm fetus after asphyxia: role of
      cardiovascular and blood flow responses.
AB  - 1. Poor perfusion of the kidneys and gut, and associated functional impairment,
      are major problems in the first days of life in very preterm infants. These
      complications can be associated with a substantial mortality and further problems
      such as reduced kidney growth and chronic renal problems in later childhood. 2.
      There is very little information, and consequently considerable debate, about how
      or even whether to improve perfusion of the vital organs of this most vulnerable
      group of babies. Current treatments simply do not consistently improve babies'
      perfusion generally or kidney and gut perfusion and function in particular. 3. In
      this review we critically examine clinical and experimental evidence that
      suggests that exposure to low oxygen levels before and during birth may be a
      significant contributor to impaired systemic perfusion, and highlight areas
      requiring further research. 4. This knowledge is essential to develop and refine
      ways of improving perfusion of the kidneys and other vital organs in premature
      babies.

PMID- 16620291
TI  - Patient age is a strong independent predictor of 13C-aminopyrine breath test
      results: a comparative study with histology, duplex-Doppler and a laboratory
      index in patients with chronic hepatitis C virus infection.
AB  - 1. Noninvasive tests for the staging of chronic hepatitis C virus (HCV) infection
      would be an attractive alternative to liver biopsy. The 13C-aminopyrine breath
      test (ABT) has been proposed for the noninvasive assessment of hepatic function
      and partly correlates with fibrosis. We aimed to investigate causes for the lack
      of discriminatory power for different degrees of hepatic fibrosis. 2. Eighty
      three patients (median age 49 years (28-78 years)) with chronic HCV infection
      underwent the ABT after an oral load of 75 mg N,N-dimethyl-13C-aminopyrine.
      Portal vein flow was assessed by duplex-Doppler and a laboratory index (aspartate
      aminotransferase to platelet ratio index or APRI) was calculated. Parameters were
      compared with liver histology. 3. The cumulative 13C-recovery differed
      significantly between patients without relevant fibrosis (fibrosis score 0-2) and
      cirrhosis (5-6), beginning after 30 min of sampling (P < 0.05). The ABT did not
      discriminate patients with fibrosis scores 3-4 from the remaining two patient
      groups. Sensitivity and specificity for the prediction of cirrhosis was 73.4
      82.8% and 63.2-68.4%, depending on the sampling time. Compared with the fibrosis
      score (P = 0.04), patient age was a highly significant independent predictor for
      the 13C-recovery (P < 0.0001). Aspartate aminotransferase to platelet ratio index
      and duplex-Doppler predicted cirrhosis with 76.6%vs. 87.5% sensitivity and
      63.2%vs. 68.4% specificity. 4. Our data suggest an age-dependent decrease of
      cytochrome P450 activity which probably accounts for the large overlap of ABT
      results that preclude clear differentiation. This is also consistent with former
      pharmacodynamic trials. Age-adapted reference ranges could improve ABT results.

PMID- 16620292
TI  - Proteomic analysis of rat aorta during atherosclerosis induced by high
      cholesterol diet and injection of vitamin D3.
AB  - 1. Atherosclerosis (AS) in rats displays important clinical similarities to human
      AS. 2. After the experimental model of AS in rat was established and using a
      proteomic approach, we compared the protein profiling of aorta tissues from
      healthy and AS rats. 3. Using two-dimensional electrophoresis (2-DE), over 1878
      protein species were separated; among them, 1239 protein spots were matched
      between different gels with average matching rate of approximately 66%. Gel
      analysis and protein characterization have identified 58 protein spots whose
      abundance is significantly altered in AS rats. 4. By using matrix-associated
      laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS) and
      NCBInr database, 46 proteins were successfully identified. Among them, 18
      proteins were of increased abundance in diseased tissues including a group of
      oxidization-related enzymes such as peroxiredoxin2 and NADH dehydrogenase Fe-S
      protein 6, components of inflammatory pathways such as lamin A, while 28 proteins
      were of decreased abundance in the diseased state, including CaM-KII inhibitory
      protein, transferring, fructose-bisphosphate aldolase. 5. We believe that these
      results would give insights into the cellular and molecular mechanisms involved
      in AS development and might lead to the discovery of novel diagnostic markers and
      new therapeutic opportunities.

PMID- 16620293
TI  - Naringin does not alter caffeine pharmacokinetics, energy expenditure, or
      cardiovascular haemodynamics in humans following caffeine consumption.
AB  - 1. Naringin, a grapefruit constituent interacts with many medications including
      caffeine, a popular weight loss supplement. The purpose of the current study was
      to identify changes in caffeine pharmacokinetics, resting energy expenditure
      (REE), oxygen consumption (VO(2)) and respiratory exchange ratio (RER) after an
      acute dosage of caffeine and naringin. 2. Using a double-blinded, counterbalanced
      design, REE, VO(2), and RER were measured before and systematically for 8 h after
      a single dosage of caffeine (CAF, 200 mg) with and without naringin (100 mg
      (CN100) or 200 mg (CN200)) in 10 apparently healthy individuals. A standardized
      meal was provided following 240-minute measurements (400 kcals; 35 g
      carbohydrate; 27 g protein; 7 g fat). 3. Caffeine, CN100, CN200 did not alter
      VO(2) or VO(2) area under the curve (137 301 +/- 8318, 139 729 +/- 9300, 134 297
      +/- 8318, mL/480 min). Resting energy expenditure (k/cals) was 10.0 +/- 1.4%
      higher with CAF versus CN200 (6.0 +/- 1.4%) and CN100 (6 +/- 1.5%) at 240 min (P
      = 0.07) which was then negated following a standardized meal. Percent change in
      RER from pre to 240 min and pre to 480 min was not different between the CAF,
      CN100, or CN200 (-0.2 +/- 1.7%, 1.7 +/- 1.7%, -2.8 +/- 1.9%). 4. Although
      caffeine alone suggests a trend of increased REE, the results of the present
      study indicate that concurrent consumption of caffeine with naringin in acute
      dosages does not affect RER, VO(2), and prevents the increase of REE in adult
      humans. The results suggest that the interaction of grapefruit juice and caffeine
      may be due to constituents of grapefruit juice other than naringin or in addition
      to naringin.

PMID- 16620294
TI  - Isoflurane and other commonly used anaesthetics do not protect the isolated
      buffer perfused mouse heart from ischemia-reperfusion injury.
AB  - 1. Some anaesthetic agents such as barbiturates and opioids possess
      cardioprotective properties in rats, rabbits, dogs and pigs. The purpose of this
      study was to evaluate the effects of some commonly used anaesthetic agents
      (pentobarbital, isoflurane and a mixture of midazolam, fentanyl and fluanisone)
      on the tolerance of the isolated mouse heart to ischaemia-reperfusion injury. 2.
      The isolated, Langendorff-perfused hearts were subjected to 45 min of global
      ischaemia followed by 60 min of reperfusion. Left ventricular pressures, heart
      rate and coronary flow were measured and infarct size was determined using
      triphenyltetrazolium staining. 3. There were no differences in haemodynamic
      variables during reperfusion between groups. Infarct size was not influenced by
      the choice of anaesthesia. 4. None of the anaesthesia protocols exerted
      significant protective effects on the ischaemic-reperfused isolated mouse heart
      performance. In mice, isoflurane as well as pentobarbital, opioids and
      benzodiazepines may be safely used for anaesthesia without a risk of protective
      side-effects in isolated mouse heart studies.

PMID- 16620295
TI  - Characterization of RWJ-351647, a novel nonpeptide vasopressin V2 receptor
      antagonist.
AB  - 1. Antagonists of the V(2) vasopressin (AVP) receptor are aquaretic agents,
      inhibiting water resorption without stimulating electrolyte excretion. In this
      set of experiments, a novel V(2) receptor antagonist, RWJ-351647, was
      characterized in vitro and in vivo. 2. RWJ-351647 displaced (3)H-AVP binding from
      cloned human V(2) and V(1A) receptors with Ki values of 1 nmol/L and 24 nmol/L.
      In assays using transfected HEK293 cells expressing either human or rat V(2)
      receptors, RWJ-351647 inhibited AVP-induced cAMP accumulation with Ki values of 3
      nmol/L and 6 nmol/L, respectively. 3. RWJ-351647 was very selective in binding
      assays and showed only weak functional antagonist activity at either the cloned
      human V(1B) and oxytocin receptors or the human platelet V(1A) receptor. No
      agonist activity was seen with the compound at any receptor. 4. Pharmacokinetic
      studies in rats showed RWJ-351647 to be 41.9% bioavailable after a single oral
      administration. After repeated daily dosing over 5 days, the oral bioavailability
      remained at 43.9% with no change in the compound peak plasma levels or clearance
      rate. 5. In efficacy studies, RWJ-351647 increased urine output and decreased
      urine osmolality with oral doses as low as 0.1 mg/kg and 1.0 mg/kg in rats and
      cynomolgus monkeys, respectively. In a multiple dose study in primates, RWJ
      351647 maintained a consistent aquaretic effect over 10 days without increasing
      sodium or potassium excretion. 6. In summary, RWJ-351647 was shown to be a
      selective and potent V(2) receptor antagonist with sustainable aquaretic activity
      in both rats and primates. The preclinical data suggest that RWJ-351647 is a
      potent and effective aquaretic agent with potential for use in diseases
      characterized by water retention.

PMID- 16620296
TI  - Effects of insulin treatment on heart rhythm, body temperature and physical
      activity in streptozotocin-induced diabetic rat.
AB  - 1. Streptozotocin (STZ)-induced diabetic cardiomyopathy is frequently associated
      with depressed diastolic/systolic function and altered heart rhythm. 2. The
      effects of insulin treatment on heart rhythm, body temperature and physical
      activity in STZ-induced diabetic rats were investigated using biotelemetry
      techniques. 3. Transmitter devices were surgically implanted in the peritoneal
      cavity of young adult male Wistar rats. Electrodes from the transmitter were
      arranged in Einthoven bipolar - Lead II configuration. Electrocardiogram,
      physical activity and body temperature data were recorded with a telemetry system
      for 10 days before STZ treatment, for 20 days following administration of STZ (60
      mg/kg) and thereafter, for 30 days while rats received daily insulin. 4. Heart
      rate, physical activity and body temperature declined rapidly 3-5 days after
      administration of STZ. Pre-STZ heart rate was 362 +/- 7 b.p.m., falling to 266 +/
      12 b.p.m. 5-15 days after STZ with significant recovery to 303 +/- 14 b.p.m. 10
      20 days after commencement of insulin. Pre-STZ body temperature was 37.5 +/-
      0.1C, falling to 37.2 +/- 0.2C 5-15 days after STZ with significant recovery to
      37.5 +/- 0.1C 10-20 days after commencement of insulin. Physical activity and
      heart rate variability were also reduced after STZ but there was no significant
      recovery during insulin replacement. 5. Defective autonomic regulation and/or
      mechanisms of control that are intrinsic to the heart may underlie disturbances
      in heart rhythm in the STZ-induced diabetic rat.

PMID- 16620297
TI  - Protective effect of paeoniflorin on immunological liver injury induced by
      bacillus Calmette-Guerin plus lipopolysaccharide: modulation of tumour necrosis
      factor-alpha and interleukin-6 MRNA.
AB  - 1. Paeoniflorin is one of the main effective components of the total glucosides
      of paeony (TGP) extracted from the root of Paeonia lactiflora which has been used
      for gynaecological problems and for cramp, pain and giddiness for over 1,500
      years in Chinese medicine. Anti-inflammatory, antioxidative, antihepatic injury
      and immunoregulatory activities of TGP have been extensively proved in our
      laboratory for many years. Our present study investigates the effects and
      mechanisms of paeoniflorin on immunological liver injury in mice. 2. A model of
      immunological liver injury was induced by tail vein injection of bacillus
      Calmette-Guerin (BCG) and lipopolysaccharide (LPS) in mice. Activities of serum
      alanine aminotransferase (ALT) were measured by biochemical methods. Hepatic
      tissue sections were stained with haematoxylin and eosin and examined under a
      light microscope. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6,
      lipopolysaccharide binding protein (LBP) and CD14 mRNA (messenger ribonucleic
      acid) expression in mouse liver were determined by semiquantitative reverse
      transcription polymerase chain reaction (RT-PCR) analysis. 3. Immunological liver
      injury induced by BCG plus LPS was successfully duplicated. Serum ALT activities
      were significantly decreased by paeoniflorin. (25, 50, 100 mg/kg). Histological
      examination demonstrated that paeoniflorin could attenuate the area and extent of
      necrosis and reduce the immigration of inflammatory cells. The increase in TNF
      alpha, LBP and CD14 mRNA expression in mouse liver after BCG and LPS injection
      was significantly decreased by paeoniflorin (100 mg/kg) and was changed by
      paeoniflorin (25, 50 mg/kg) at different time-point. The augmentation of IL-6
      mRNA in mouse liver was markedly increased by paeoniflorin at 1 h and 3 h after
      LPS injection. 4. Paeoniflorin could significantly protect against immunological
      liver injury in mice. TNF-alpha, IL-6, LBP and CD14 mRNA expression in mouse
      liver may be involved in BCG plus LPS induced liver injury. The protective
      mechanism of paeoniflorin might be partially related to modulation of TNF-alpha,
      IL-6, LBP and CD14 mRNA expressions in mouse liver.

PMID- 16620298
TI  - Acute dilatory and negative inotropic effects of homocysteine are inhibited by an
      adenosine blocker.
AB  - 1. Previous studies have shown that homocysteine elicits acute negative inotropic
      and coronary vasodilatory effects in rat hearts. In addition, this earlier work
      suggested that the inotropic action is mediated via an endothelium-derived agent
      that is neither nitric oxide (NO) nor a cyclooxygenase product, while the
      coronary actions were found to be antagonized by the NOS inhibitor l-NNA. Current
      experiments, which utilized coronary-perfused rat hearts, were designed to
      determine if muscarinic or adenosine receptors are involved in these acute
      actions of homocysteine. 2. Left ventricular developed pressure was used as a
      measure of systolic function in electrically paced, Langendorff-perfused heart
      with coronary pressure being used to monitor coronary vascular tone. Acute
      effects of homocysteine (10-300 micromol/L) were examined in the presence and
      absence of 1 yen 10(-6) mol atropine or 7 yen 10(-5) mol 8-(p-sulfophenyl)
      theophylline (SPT), a non-selective adenosine receptor antagonist. 3. Atropine
      had no effect on either the inotropic or vascular actions of homocysteine. In
      contrast, SPT partially antagonized both actions of the amino acid with the
      antagonism of the vasodilation being much greater than its inhibition of the
      negative inotropic effect. Experiments with adenosine demonstrated that the
      selected dose of SPT elicited marked rightward shifts in the dose-response curves
      for both the inotropic and vascular actions. 4. Current results suggest that
      adenosine plays a role in both the negative inotropic and vasodilatory actions of
      homocysteine. However, the relatively minor antagonistic action of SPT on the
      inotropic effect of homocysteine suggests that additional endothelium-derived
      mediators underlie its effects on contractility.

PMID- 16620299
TI  - Direct effects of quercetin on impaired reactivity of spontaneously hypertensive
      rat aortae: comparative study with ascorbic acid.
AB  - 1. There is a growing interest in the anti-oxidant characteristics and use of
      flavonoids in the management of cardiovascular diseases. The cardiovascular
      mechanism of action of these plant derivatives remains controversial. This study
      compared the effects of the flavonoid quercetin with those of the anti-oxidant
      vitamin ascorbic acid (vitamin C) on the reactivity of aortic rings from
      spontaneously hypertensive rats (SHR). 2. The phenylephrine (PE)-induced
      contractile and the endothelium-dependent and independent relaxant responses of
      aortic rings from 21 to 22 week old SHR and age-matched normotensive Wistar (WKY)
      rats were observed in the presence of quercetin or ascorbic acid. All the
      experiments were performed in the presence of the cyclooxygenase inhibitor,
      indomethacin (10 micromol/L). 3. The endothelium-dependent and independent
      relaxations to acetylcholine (ACh) and sodium nitroprusside (SNP), respectively,
      were significantly lesser in the SHR compared to the WKY tissues whereas the
      contractile responses to PE were similar in both tissues. Pretreatment of WKY
      rings with quercetin or ascorbic acid had no effect on the responses to ACh or
      PE. In the SHR tissues, however, quercetin or ascorbic acid significantly
      improved the relaxation responses to ACh and reduced the contractions to PE with
      greater potency for quercetin. Both compounds lacked any effects on the responses
      to SNP in either aortic ring types. N(omega)-nitro-L-arginine methyl ester (l
      NAME, 10 micromol/L) significantly attenuated the vasodepressor effects of
      quercetin and ascorbic acid, raising the responses to PE to a level similar to
      that observed in the control SHR tissues. In l-NAME pretreated aortic rings,
      quercetin and ascorbic acid inhibited the contractile responses to PE with the
      same magnitude in WKY and SHR tissues. 4. The present results suggest that acute
      exposure to quercetin improves endothelium-dependent relaxation and reduces the
      contractile responses of hypertensive aortae with a greater potency than ascorbic
      acid. This suggests a better vascular protection with this flavonoid than
      ascorbic acid in the SHR model of hypertension and possibly in human
      cardiovascular diseases.

PMID- 16620300
TI  - Therapeutic effect of green tea extract on advanced glycation and cross-linking
      of collagen in the aorta of streptozotocin diabetic rats.
AB  - 1. The therapeutic effect of green tea extract (GTE) on the aortic collagen
      content and its characteristics were investigated in streptozotocin diabetic
      rats. 2. Diabetes was induced in rats by a single intra peritoneal injection of
      streptozotocin (60 mg/kg bodyweight). Six weeks after diabetes induction, GTE was
      administered orally for four weeks (300 mg/kg bodyweight daily). Systolic blood
      pressure, blood glucose, anti-oxidant status, collagen content, extent of
      glycation, collagen linked fluorescence and aortic collagen solubility pattern
      were determined in experimental rats. 3. At the end of the experimental period,
      there was a significant increase in the systolic blood pressure and blood glucose
      in diabetic rats. The lipid peroxides increased whereas glutathione and vitamin C
      levels were decreased in the serum of diabetic rats. The collagen content, extent
      of glycation, the advanced glycation end products (AGEs) and degree of cross
      linking were increased in the aorta of diabetic rats. 4. The oral administration
      of GTE to diabetic rats significantly reduced the systolic blood pressure and
      blood glucose. The level of lipid peroxides reduced and the content of
      glutathione and vitamin C increased in the serum of GTE treated diabetic rats.
      Green tea extract also impede the accumulation of aortic collagen, extent of
      glycation, formation of AGEs and cross-linking of collagen in diabetic rats. The
      antihyperglycemic, anti-oxidant and antiglycating effects of GTE ascribed for
      these beneficial effects. In conclusion, green tea may have therapeutic effect in
      the treatment of cardiovascular complications characterized by increased AGE
      accumulation and protein cross-linking associated with diabetes.

PMID- 16620301
TI  - Early structural changes of aortic wall in sinoaortic-denervated rats.
AB  - 1. The present work was designed to observe the early structural changes in the
      aortic wall in Sprague-Dawley rats 1, 2 and 4 weeks after sinoaortic denervation
      (SAD). 2. Rats were examined 1, 2 and 4 weeks after SAD. Blood pressure (BP) was
      recorded in the conscious state. The thoracic aortas were taken for
      investigations, including: light microscopy, electron microscopy,
      immunohistochemistry and terminal deoxynucleotidyl transferase (TdT)-mediated
      dUTP nick-end labelling (TUNEL). 3. Blood pressure variability (BPV) was
      significantly increased in the SAD groups 1, 2 and 4 after the operation when
      compared with the sham-operated ones. 4. Two weeks after SAD the percentage
      proportion of smooth muscle cell density (SMC%) was obviously increased. 5. Four
      weeks after SAD: the SMC%, percentage proportion of collagen density (CD%) and
      aortic wall thickness (WT) were obviously increased with vascular smooth muscle
      cells blebbing concomitantly. Endothelial cells showed degenerative changes and
      swelling with blebbing of the cell membrane and increased condensation of
      peripheral nuclear chromatin and cytoplasmic vacuolization. It was also found
      that the number of apoptotic endothelial cells was increased and expression of
      eNOS was reduced. 6. This is the first study that shows the time-course of aortic
      wall and endothelial cell changes induced by SAD. Increased BPV might be the
      priming factor in the development of organ damage induced by SAD.

PMID- 16620302
TI  - In vitro neurotoxic and myotoxic effects of the venom from the black whip snake
      (Demansia papuensis).
AB  - 1. Black whip snakes belong to the family elapidae and are found throughout the
      northern coastal region of Australia. The black whip snake (Demansia papuensis)
      is considered to be potentially dangerous due to its size and phylogenetic
      distinctiveness. Previous liquid chromatography-mass spectrometry analysis of D.
      papuensis venom indicated a number of components within the molecular mass ranges
      compatible with neurotoxins. For the first time, this study examines the in vitro
      neurotoxic and myotoxic effects of the venom from D. papuensis. 2. Venom (10
      microg/mL) caused significant inhibition of twitches elicited by stimulation (0.2
      ms, 0.1 Hz, supramaximal V) of motor nerves in the chick biventer cervicis nerve
      muscle preparation. This neurotoxic effect, which was postsynaptic in origin, was
      weak in comparison to that of most other Australian elapids. Prior addition (10
      min) of polyvalent (PSAV) or tiger snake (TSAV) antivenom (5 units/mL) prevented
      venom-induced twitch inhibition. Addition of PSAV (5 units/mL) at t(50) failed to
      reverse the inhibitory effect but prevented further inhibition of nerve-mediated
      twitches. 3. The venom (20-50 microg/mL) is also myotoxic as indicated by a
      slowly developing contracture and inhibition of twitches elicited by direct
      stimulation (2 ms, 0.1 Hz, supramaximal V, in the presence of tubocurarine 10
      micromol/L) of the chick biventer muscle. This activity was confirmed by
      histological examination of the muscle. 4. Fractionation and characterization of
      venom components is required to further investigate the reasons for the weak
      neurotoxic activity of D. papuensis venom.

PMID- 16620303
TI  - Atorvastatin prevented and partially reversed adrenocorticotropic hormone-induced
      hypertension in the rat.
AB  - 1. Adrenocorticotropic hormone (ACTH)-induced hypertension is associated with
      nitric oxide (NO) deficiency and increased oxidative stress. Atorvastatin (Ato),
      an HMG-Co-enzyme-A reductase inhibitor has been reported to enhance availability
      of NO. The aim of the study was to assess whether pretreatment with Ato would
      prevent the development of ACTH-induced hypertension and whether established ACTH
      induced hypertension could be reversed with subsequent administration of Ato in
      rats. 2. Male Sprague-Dawley rats (n = 60) were treated with Ato (30 mg/kg per
      day in drinking water) or tap water for 15 days. ACTH (0.2 mg/kg per day s.c) or
      saline was started 4 days after Ato treatment or non-treated rats and continued
      for 11-13 days (prevention study). In the reversal study, Ato was given on day 8
      of ACTH/Saline treatment for 5 days. Systolic blood pressure (SBP) was measured
      on alternate days using the tail cuff method. 3. Adrenocorticotropic hormone
      treatment increased SBP (110 +/- 2-136 +/- 2 mmHg, P < 0.001) and aortic
      superoxide production (P < 0.001). Ato alone did not alter SBP, but Ato
      pretreatment prevented ACTH-induced hypertension compared with that in rats
      treated with ACTH alone (118 +/- 2 and 136 +/- 2 mmHg, respectively, P cent <
      0.01). Ato partially reversed ACTH-induced hypertension (124 +/- 3 and 136 +/- 2
      mmHg, respectively, P cent < 0.05). Plasma nitrate/nitrite (NOx) was decreased in
      ACTH-treated rats compared with saline treated rats (6.6 +/- 0.4 saline and 4.5
      +/- 0.5 micromol/L ACTH, P < 0.001). Atorvastatin affected neither plasma NOx nor
      aortic superoxide production. 4. Atorvastatin prevented and partially reversed
      ACTH-induced hypertension in the rat.

PMID- 16620304
TI  - Upregulation of 14-3-3 isoforms in acute rat myocardial injuries induced by burn
      and lipopolysaccharide.
AB  - 1. Burn-induced myocardial injuries can be acute due to loss of body fluid and
      blood redistribution, and subacute due to pathogenic toxins of infecting
      bacteria. The goal of this study was to examine expression of 14-3-3 in the
      injured myocardium. 2. Myocardial injury models were created in vivo by
      subjecting rats to severe burn and administration of lipopolysaccharide. RT-PCR
      and Western blotting were employed to assess the expression of 14-3-3 proteins
      and messenger ribonucleic acid (mRNA) for 14-3-3eta and gamma in the myocardium,
      respectively. 3. In the two models, we found that 14-3-3 proteins were induced in
      a time-dependent fashion. Such a change is at least in part attributed to
      increases in mRNAs for 14-3-3gamma and eta. In contrast to 14-3-3xi, whose mRNA
      was not detectable in the heart, mRNA for 14-3-3gamma was found significantly
      elevated between 24-48 h after burn. 14-3-3eta mRNA exhibited a marked increase
      at 3 h continuing to 12 h and then decreased nearly to a normal level after 48 h.
      In lipopolysaccharide-treated intact rats, 14-3-3gamma mRNA in myocardium showed
      a significant increase, reaching a peak at 4 h, followed by a decrease at 6 h. In
      contrast, 14-3-3eta mRNA had a slight increase without significance. 4. Our
      results suggest that 14-3-3 may play a role in both acute and subacute (postburn
      infectious) phases of severe burn.

PMID- 16620305
TI  - Effects of oral beraprost sodium, a prostaglandin I2 analogue, on endothelium
      dependent vasodilatation in the forearm of patients with coronary artery disease.
AB  - 1. Previous clinical studies with prostaglandin I(2) (PGI(2)) analogue beraprost
      sodium suggested the potential effects on protection of cardiovascular events in
      patients with peripheral artery disease. Although the mechanism is not well
      known, experimental studies have shown protective effects of endothelial cells.
      This study was designed to examine the effects of beraprost sodium on vascular
      endothelial function in the forearm of patients with coronary artery disease. 2.
      Beraprost sodium (120 microg/day) was orally administered to 14 coronary artery
      disease patients for 4 weeks and then stopped for 4 weeks. Eleven control
      patients did not receive beraprost sodium treatment. Reactive hyperemia was
      induced in the forearm, endothelium-dependent vasodilatation was assessed by
      plethysmography, and urinary 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha))
      was measured at baseline, 4 weeks and 8 weeks. 3. Both groups had similar
      reactive hyperemic responses at baseline. In the control group, reactive
      hyperemic response and urinary 8-iso-PGF(2alpha) remained unchanged for 8 weeks.
      In the beraprost group, maximum forearm blood flow increased significantly (P =
      0.01) after 4 weeks of treatment and returned to baseline at 8 weeks. Duration of
      hyperemia increased significantly (P = 0.003) after 4 weeks, and remained greater
      than baseline at 8 weeks (P = 0.02). Urinary 8-iso-PGF(2alpha) decreased
      significantly (P = 0.03) after 4 weeks, and tended to be lower at 8 weeks (P =
      0.07). Changes in reactive hyperemia correlated weakly but significantly with
      changes in 8-iso-PGF(2alpha) (P < 0.001). 4. Beraprost sodium decreased oxidative
      stress and improved forearm endothelium-dependent vasodilatation in coronary
      artery disease patients. The favorable effects on vascular endothelium could
      potentially lead to a decrease in vascular events.

PMID- 16620306
TI  - Fluvastatin increases heterotopically induced ossicles in mice.
AB  - 1. The aim of the present study was to evaluate the influence of fluvastatin (3
      hydroxy-3-methylglutarylcoenzyme A reductase inhibitor) on heterotopic
      ossification (HO) induced by HeLa cells. 2. C57Bl/6 mice were injected with 3 x
      10(6) HeLa cells into right thigh muscles. Mice in the experimental group
      received fluvastatin 1.2 mg/kg per day for 17 consecutive days, while mice in the
      control group received placebo. Intact mice served as an additional control.
      Seventeen days post-HeLa cell grafting, blood samples were collected to measure
      total serum cholesterol (TC), triglycerides (TG), low density lipoprotein
      cholesterol and alkaline phosphatase (AP). 3. In all animals injected with HeLa
      cells, the mass of mineral deposited in the induced ossicle was established after
      hydrolysis of soft tissues surrounding the induced ossicles. In fluvastatin
      treated mice, the mass of mineral deposited in heterotopically induced ossicles
      was significantly increased, when compared to mice receiving placebo. This was
      followed by a significant decrease of TG concentration; whereas the levels of
      serum AP were not significantly affected. 4. These results indicate that
      administration of statins may affect heterotopic ossification. This may also have
      clinical implication, because patients predisposed to HO and receiving statins
      during hypocholesterolemic treatment, may be at even greater risk of HO.

PMID- 16620307
TI  - Effects of exercise-induced arterial hypoxaemia on limb muscle fatigue and
      performance.
AB  - 1. Reductions in arterial O(2) saturation (-5% to -10%S(a)o(2) below rest) occur
      over time during sustained heavy-intensity exercise in a normoxic environment,
      caused primarily by the effects of acid pH and increased temperature on the
      position of the HbO(2) dissociation curve. 2. We prevented the desaturation
      incurred during exercise at approximately 90% VO(2 MAX) via increased fraction of
      inspired O(2) (F(i)o(2)) (0.23 to 0.29) and showed that exercise time to
      exhaustion was increased. 3. We used supramaximal magnetic stimulation (1-100 Hz)
      of the femoral nerve to test for quadriceps fatigue. We used mildly hyperoxic
      inspirates (F(i)o(2) 0.23 to 0.29) to prevent O(2) desaturation. We then compared
      the amount of quadriceps fatigue incurred following cycling exercise at S(a)o(2)
      91% vs 98% with each trial carried out at identical work rates and for equal
      durations. 4. Preventing the normal exercise-induced O(2) desaturation prevented
      about one-half the amount of exercise-induced quadriceps fatigue; plasma lactate
      and effort perception were also reduced. In a subset of less fit subjects who
      showed only minimal arterial hypoxaemia during sustained exercise (S(a)o(2)
      approximately 95%), breathing a mildly hypoxic inspirate (F(i)o(2) 0.17; S(a)o(2)
      approximately 88%) exacerbated the quadriceps fatigue. 5. We conclude that the
      normal exercise-induced O(2) desaturation during heavy-intensity endurance
      exercise contributes significantly to exercise performance limitation in part
      because of its effect on locomotor muscle fatigue.

PMID- 16620308
TI  - Exercise and skeletal muscle glucose transporter 4 expression: molecular
      mechanisms.
AB  - 1. Skeletal muscle is a highly plastic tissue that has a remarkable ability to
      adapt to external demands, such as exercise. Many of these adaptations can be
      explained by changes in skeletal muscle gene expression. A single bout of
      exercise is sufficient to induce the expression of some metabolic genes. We have
      focused our attention on the regulation of glucose transporter isoform 4 (GLUT-4)
      expression in human skeletal muscle. 2. Glucose transporter isoform 4 gene
      expression is increased immediately following a single bout of exercise, and the
      GLUT-4 enhancer factor (GEF) and myocyte enhancer factor 2 (MEF2) transcription
      factors are required for this response. Glucose transporter isoform enhancer
      factor and MEF2 DNA binding activities are increased following exercise, and the
      molecular mechanisms regulating MEF2 in exercising human skeletal muscle have
      also been examined. 3. These studies find possible roles for histone deacetylase
      5 (HDAC5), adenosine monophosphate-activated protein kinase (AMPK), peroxisome
      proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) and p38
      mitogen-activated protein kinase (MAPK) in regulating MEF2 through a series of
      complex interactions potentially involving MEF2 repression, coactivation and
      phosphorylation. 4. Given that MEF2 is a transcription factor required for many
      exercise responsive genes, it is possible that these mechanisms are responsible
      for regulating the expression of a variety of metabolic genes during exercise.
      These mechanisms could also provide targets for the treatment and management of
      metabolic disease states, such as obesity and type 2 diabetes, which are
      characterized by mitochondrial dysfunction and insulin resistance in skeletal
      muscle.

PMID- 16620309
TI  - Evidence for a supraspinal contribution to human muscle fatigue.
AB  - 1. Muscle fatigue can be defined as any exercise-induced loss of ability to
      produce force with a muscle or muscle group. It involves processes at all levels
      of the motor pathway between the brain and the muscle. Central fatigue represents
      the failure of the nervous system to drive the muscle maximally. It is defined as
      a progressive exercise-induced reduction in voluntary activation or neural drive
      to the muscle. Supraspinal fatigue is a component of central fatigue. It can be
      defined as an exercise-induced decline in force caused by suboptimal output from
      the motor cortex. 2. When stimulus intensity is set appropriately, transcranial
      magnetic stimulation (TMS) over the motor cortex during an isometric maximal
      voluntary contraction (MVC) of the elbow flexors commonly evokes a small twitch
      like increment in flexion force. This increment indicates that, despite the
      subject's maximal effort, motor cortical output at the moment of stimulation was
      not maximal and was not sufficient to drive the motoneurons to produce maximal
      force from the muscle. An exercise-induced increase in this increment
      demonstrates supraspinal fatigue. 3. Supraspinal fatigue has been demonstrated
      during fatiguing sustained and intermittent maximal and submaximal contractions
      of the elbow flexors where it accounts for about one-quarter of the loss of force
      of fatigue. It is linked to activity and the development of fatigue in the tested
      muscles and is little influenced by exercise performed by other muscles. 4. The
      mechanisms of supraspinal fatigue are unclear. Although changes in the behaviour
      of cortical neurons and spinal motoneurons occur during fatigue, they can be
      dissociated from supraspinal fatigue. One factor that may contribute to
      supraspinal fatigue is the firing of fatigue-sensitive muscle afferents that may
      act to impair voluntary descending drive.

PMID- 16620310
TI  - Mindfulness-based psychotherapies: a review of conceptual foundations, empirical
      evidence and practical considerations.
AB  - OBJECTIVE: This paper, composed by an interest group of clinicians and
      researchers based in Melbourne, presents some background to the practice of
      mindfulness-based therapies as relevant to the general professional reader. We
      address the empirical evidence for these therapies, the principles through which
      they might operate, some practical questions facing those wishing to commence
      practice in this area or to refer patients into mindfulness-based therapies, and
      some considerations relevant to the conduct and interpretation of research into
      the therapeutic application of mindfulness. METHOD: Databases (e.g. PsycINFO,
      MEDLINE) were searched for literature on the impact of mindfulness interventions,
      and the psychological and biological mechanisms that underpin the effects of
      mindfulness practice. This paper also draws upon the clinical experience of the
      author group. RESULTS: Mindfulness practice and principles have their origins in
      many contemplative and philosophical traditions but individuals can effectively
      adopt the training and practice of mindfulness in the absence of such traditions
      or vocabulary. A recent surge of interest regarding mindfulness in therapeutic
      techniques can be attributed to the publication of some well-designed empirical
      evaluations of mindfulness-based cognitive therapy. Arising from this as well as
      a broader history of clinical integration of mindfulness and Western
      psychotherapies, a growing number of clinicians have interest and enthusiasm to
      learn the techniques of mindfulness and to integrate them into their therapeutic
      work. This review highlights the importance of accurate professional awareness
      and understanding of mindfulness and its therapeutic applications. CONCLUSIONS:
      The theoretical and empirical literatures on therapeutic applications of
      mindfulness are in states of significant growth and development. This group
      suggests, based on this review, that the combination of some well-developed
      conceptual models for the therapeutic action of mindfulness and a developing
      empirical base, justifies a degree of optimism that mindfulness-based approaches
      will become helpful strategies to offer in the care of patients with a wide range
      of mental and physical health problems.

PMID- 16620311
TI  - Psychotherapy in the medically ill: a commentary.
AB  - OBJECTIVE: To overview the field of psychotherapy in the medically ill. Rather
      than attempting a systematic review of this very extensive area, the article
      seeks to capture some of the main threads and issues of importance. METHOD: The
      subject is looked at under four headings: (i) which illnesses have attracted
      research interest in psychotherapy; (ii) which outcome measures have been chosen;
      (iii) which modes of intervention have been used; and (iv) finally a review of
      the methodology and the results obtained. RESULTS: Some illnesses have attracted
      much more psychotherapeutic interest than others; the differences are haphazard.
      Outcome measures on the whole have focused on coping with illness and
      psychological distress, with a smaller number looking at disease outcome. Only
      short-term changes have been sought in the main. The most commonly used
      modalities of therapy have been cognitive-behavioural; additionally, supportive
      information-giving and group therapy have been trialled. Benefit in terms of all
      these have been reported, but the majority of studies are weakened by major
      methodological shortcomings. CONCLUSION: There is an overall paucity of well
      designed studies that clearly demonstrate psychotherapy as an efficacious
      treatment in the medically ill. The field is hampered by the lack of a clear
      conceptual thread recognizing the long-term and diverse experience of patients
      with medical illness and relating this to the question of the part psychotherapy
      should play. Future work needs to concentrate on appropriate selection of
      patients who might benefit, as well as including a wider range of more clinically
      relevant outcome measures and more stringent methodology.

PMID- 16620313
TI  - Symbolism of community II: the boundary between community mental health
      professional and community.
AB  - OBJECTIVE: To study the symbolism of community as understood and practised within
      a mental health Crisis and Assessment Service in an Australian city. THEORETICAL
      APPROACHES: The paper draws on anthropological theories of symbolism, boundary
      work and social networks. METHOD: Ethnographic fieldwork techniques were employed
      for data collection. Ethnographic analysis was then applied to these data.
      RESULTS: In mental health practice, rules of professional behaviour established a
      boundary that prohibited mental health professionals from social engagement with
      members of the community they served. Ethical imperatives prevented them from
      forming interpersonal bonds with their clients. Rules of privacy and
      confidentiality meant that they could not relate to the client's social network
      as a whole. CONCLUSIONS: The companion to this paper identified a summarizing
      symbol, which we designated community, and it specified the social values it
      represented when appropriated to the task of drawing a boundary between hospital
      and community. This paper specifies additional social values represented by
      community when it is appropriated to the task of drawing a boundary between
      community mental health professionals and the community.

PMID- 16620312
TI  - Symbolism of community I: the boundary between hospital and community.
AB  - OBJECTIVE: To study the symbolism of community as understood and practised in a
      mental health Crisis and Assessment Service in an Australian city. THEORETICAL
      APPROACHES: The paper draws on anthropological theories of symbolism and boundary
      work. METHOD: Ethnographic fieldwork techniques were employed for data
      collection. Ethnographic analysis was then applied to these data. RESULTS: In
      mental health practice, community is primarily defined in contradistinction to
      hospital. Narratives about community, including an orthodox version and a
      sceptical counter-narrative, revolve around this community-hospital boundary.
      CONCLUSIONS: This analysis identifies a key symbol, which we have designated
      community, and enumerates the social values that comprise it.

PMID- 16620314
TI  - Using participatory action research in a community-based initiative addressing
      complex mental health needs.
AB  - OBJECTIVE: This paper describes the first phase of a larger project that utilizes
      participatory action research to examine complex mental health needs across an
      extensive group of stakeholders in the community. METHOD: Within an objective
      qualitative analysis of focus group discussions the social ecological model is
      utilized to explore how integrative activities can be informed, planned and
      implemented across multiple elements and levels of a system. Seventy-one primary
      care workers, managers, policy-makers, consumers and carers from across the
      southern metropolitan and Gippsland regions of Victoria, Australia took part in
      seven focus groups. All groups responded to an identical set of focusing
      questions. RESULTS: Participants produced an explanatory model describing the
      service system, as it relates to people with complex needs, across the levels of
      social ecological analysis. Qualitative themes analysis identified four priority
      areas to be addressed in order to improve the system's capacity for working with
      complexity. These included: (i) system fragmentation; (ii) integrative case
      management practices; (iii) community attitudes; and (iv) money and resources.
      CONCLUSIONS: The emergent themes provide clues as to how complexity is
      constructed and interpreted across the system of involved agencies and interest
      groups. The implications these findings have for the development and evaluation
      of this community capacity-building project were examined from the perspective of
      constructing interventions that address both top-down and bottom-up processes.

PMID- 16620315
TI  - Quality of life and psychopathology: investigations into their relationship.
AB  - OBJECTIVE: Quality of life (QOL) has become a topic of growing interest in
      medical and psychiatric practice in general, and in research in particular.
      Although the body of knowledge about the complex relationship between QOL and
      psychiatric disorders is growing, understanding this relationship still remains
      difficult. Therefore, the aim of the present study was to get more and new
      insights into this relationship. It was hypothesized that QOL would be negatively
      related to the presence as well as the severity of psychopathology. METHOD: A
      random sample of Dutch adult psychiatric outpatients (n=410) completed the World
      Health Organization Quality of Life assessment instrument, abbreviated version
      (WHOQOL-Bref). In addition, DSM-IV axis I and II diagnoses were obtained.
      Comparisons were made between scores of the psychiatric outpatients, diagnostic
      subgroups within this population, and the scores of a general population.
      RESULTS: Compared with the general population, psychiatric outpatients scored
      significantly worse on all aspects of QOL. Within the group of outpatients,
      participants with DSM-IV diagnoses had worse scores than those without.
      Participants with comorbidity had the worst QOL. CONCLUSIONS: It is concluded
      that QOL scores are negatively related to both the presence and the severity of
      psychopathology, and that the presence of a personality disorder plays a role in
      subjectively experienced QOL.

PMID- 16620316
TI  - Effect of post-migration detention on mental health among Afghan asylum seekers
      in Japan.
AB  - OBJECTIVES: Afghan asylum seekers in Japan were increasingly subject to detention
      following the terrorist attack in New York in September 2001, yet little is
      reported about the net impact of the detention on their mental health. We
      examined this by comparing asylum seekers who had once been detained in post
      migration and their non-detained counterparts. METHOD: We conducted a cross
      sectional survey in 2002/03 among asylum seekers from Afghanistan who were in the
      process of refugee application in Japan. We contacted them through their lawyers
      or non-governmental organizations. Of 73 contacted, 55 agreed to participate.
      Anxiety and depression were measured using the Hopkins Symptom Checklist 25, and
      posttraumatic stress disorders (PTSD) and past traumatic experiences were studied
      with the Harvard Trauma Questionnaire. These mental disorders were scored on a 4
      point scale; the average symptom score of 4 indicates the worst mental health
      status. RESULTS: Respondents reported a mean (SD) of 10 (4.0) pre-migration
      traumas. Since their arrival in Japan, 18 (33%) had once been detained. Trauma
      exposures and other characteristics of those detained were not significantly
      different from those not detained, whereas the symptom scores of anxiety (2.91),
      depression (2.75) and PTSD (2.90) among those detained were higher than among
      those not detained (2.30, 2.41, 2.34 respectively). Multiple regression analyses
      revealed independent adverse effects of post-migration detention, alongside
      exposure to greater trauma and living alone, and the effects were comparable
      between these variables. CONCLUSION: The post-migration detention of Afghan
      asylum seekers in Japan was independently related to their worsened mental
      health.

PMID- 16620317
TI  - Pathways to the first contact with specialist mental health care.
AB  - OBJECTIVE: To examine the pathways to mental health care followed by patients
      presenting for the first time to community- and hospital-based services and the
      degree to which individual characteristics, cultural background, illness type,
      severity and service-related variables influence the time and pathways taken to
      reach care. METHOD: One hundred and forty-six consecutive Australian-born, Asian
      and Arabic-speaking patients making their first lifetime contact with mental
      health services in two area health regions were included. Symptom severity was
      assessed using the Health of the Nations Outcome Scales. Illness explanatory
      models, social support, English-language proficiency and acculturation were also
      assessed. RESULTS: An average of three professional consultations were made prior
      to first contact with public mental health services. Family physicians occupied a
      pivotal role in the help-seeking pathway with 53% of patients consulting a
      general practitioner. The median time taken to reach specialist mental health
      services was 6 months, with significantly shorter time for patients with
      psychotic disorders. Individual variables such as gender, social support,
      ethnicity and English fluency were not associated with delays in receiving public
      mental health care. Ethnicity was associated with lower utilization of allied
      health professionals. CONCLUSIONS: The data suggest that social and cultural
      factors influence the range of professionals consulted by those with a mental
      illness but do not delay their presentation to public mental health services.

PMID- 16620318
TI  - Survey of quality of life and related risk factors for a Taiwanese village
      population 3 years post-earthquake.
AB  - OBJECTIVE: To investigate quality of life (QOL) and related risk factors in
      Taiwanese earthquake survivors diagnosed with different psychiatric disorders 3
      years after the 1999 Chi-Chi earthquake. METHOD: This study was a population
      survey. Trained assistants used the Medical Outcomes Study Short Form-36 (MOS SF
      36) and questionnaires to interview 405 respondents (189 men and 216 women) aged
      16 years or older, who had been exposed to the earthquake. Psychiatrists
      interviewed the same respondents using the Mini-International Neuropsychiatric
      Interview, with an adjusted response rate of 70.2%. RESULTS: The prevalence range
      for psychiatric disorders in the earthquake survivors was 0.2-7.2% 3 years after
      the Chi-Chi earthquake, with rates for major depression (MD) and posttraumatic
      stress disorder (PTSD) of 6.4% and 4.4%, respectively. The QOL scores for the
      PTSD/MD group were lower than for the other two diagnostic groups, as determined
      by assessment of physical and mental aspects of functional integrity from MOS SF
      36 scores. The predictors for poor QOL were age, female gender, economic
      problems, physical illness, subjective assessment of memory and social-activity
      decline and diagnosis of PTSD or MD. CONCLUSION: The QOL for earthquake survivors
      with psychiatric disorders, especially PTSD or MD, was inferior compared with the
      mentally healthy analogues, with contemporaneous decreases in mental and physical
      function scores across the QOL subscales. The persistence of long-term economic
      problems was one of many important factors affecting QOL.

PMID- 16620319
TI  - Changes in private sector electroconvulsive treatment in Australia.
AB  - OBJECTIVES: This paper reports on changes, over time and between states, in the
      use of electroconvulsive therapy (ECT) in the private psychiatric sector in
      Australia between 1984 and 2004. METHOD: Data for ECT services, and all
      specialist psychiatry services provided under the Medicare system, have been
      analysed in absolute numbers and as utilization rates. RESULTS: Changes in the
      use of ECT over time are different from other services provided by private
      psychiatrists. As in other countries, the use of ECT initially declined in period
      studied but has increased in recent years. In addition, there is a clear pattern
      of differential use of ECT between the states and territories. CONCLUSIONS: This
      descriptive study cannot 'explain' the results obtained: other data, incorporated
      into an explanatory model using regression analysis, are needed to determine the
      factors underlying the utilization patterns obtained in this study. Thus, further
      work is needed. Furthermore, it is important to analyse data at a lower level of
      geographical aggregation than that of the state/territory: this (state/territory)
      aggregation conceals differences in utilization between metropolitan, minor city,
      rural and remote regions of the country.

PMID- 16620320
TI  - A survey of publicly funded aged psychiatry services in Australia and New
      Zealand.
AB  - OBJECTIVE: To map the size and distribution of publicly funded aged psychiatry
      (psychogeriatric) services in Australia and New Zealand in 2003. METHOD: Services
      were tracked exhaustively through personal, professional and academic contacts,
      electronic searches and word-of-mouth. Directors or managers of services were
      asked to complete a brief questionnaire concerning their locality, services,
      staff profile and patient contacts. RESULTS: Services varied widely with respect
      to their numbers, size and community outreach. Victoria was the only Australian
      state to provide specialist, multidisciplinary aged psychiatry teams with
      community, acute inpatient and residential arms in all its major cities. New
      South Wales, the state with the largest aged population, performed relatively
      poorly on most indicators. New Zealand performed relatively well despite its
      small size and widely dispersed population. CONCLUSIONS: Publicly funded aged
      mental health services are effective and reach frail, multiply disabled old
      people who cannot access private psychiatrists and are often overlooked by
      services for younger adults. At the time of our survey, such services were
      distributed in Australia in a highly inequitable fashion.

PMID- 16620321
TI  - Dissociative identity disorder and temporal lobe involvement: replication and a
      cautionary note.

PMID- 16620322
TI  - Olanzapine-induced oculogyric crisis.

PMID- 16620323
TI  - Neuropsychological disturbances and cerebral blood flow in bipolar disorder.

PMID- 16620327
TI  - Systematic review of the safety of electrosurgery for tonsillectomy.
AB  - In the meta-analysis models, compared with cold steel dissection with ties/packs
      haemostasis (reference technique): * Bipolar diathermy dissection and haemostasis
      was associated with statistically significant lower odds of primary haemorrhage
      (OR 0.13, 95% CrI 0.03 to 0.51), including primary haemorrhage requiring return
      to theatre (OR 0.002, 95% CrI <0.001 to 0.26). * Coblation was associated with
      statistically significant higher odds of secondary haemorrhage requiring return
      to theatre (OR 33.82, 95% CrI 1.25 to 5676.00). * Monopolar and bipolar diathermy
      dissection and haemostasis (OR 4.12, 95% CrI 1.12 to 14.67; OR 2.86, 95% CrI 1.12
      to 8.02, respectively), coblation (OR 3.75, 95% CrI 1.29 to 12.12), and cold
      steel dissection with monopolar or bipolar diathermy haemostasis (OR 4.83, 95%
      CrI 1.56 to 15.95; OR 9.18, 95% CrI 3.09 to 30.53, respectively) were all
      associated with statistically significant higher odds of secondary haemorrhage. *
      In deciding which technique to employ, factors to consider include patient
      characteristics, the underlying risk of primary or secondary haemorrhage, which
      is regarded as likely to be more serious, and the clinical significance of the
      observed differences in haemorrhage rates across techniques.

PMID- 16620328
TI  - A review of sinonasal outcome scoring systems - which is best?
AB  - * In patients undergoing endoscopic sinus surgery for chronic rhinosinusitis,
      there is a lack of a universally accepted system for the evaluation of outcome. *
      This makes critical comparison between results less meaningful. * To determine
      the most suitable sinonasal outcome scoring system for use in our own practice,
      we reviewed the available literature and known systems in existence. * We
      analysed 15 known disease-specific sinonasal outcome indices with emphasis on
      reliability, validity and responsiveness. * We concluded by choosing one quality
      of life outcome tool for our departmental use, the Sinonasal Outcome Test-22, due
      to its reliability, validity, responsiveness and ease of use. * It has been
      validated to distinguish between disease-affected patient groups and those
      without rhinosinusitis, demonstrate a worse score if the condition gets worse and
      show an appropriateness of items and scales in the questionnaire. This has been
      demonstrated in 3128 British patients.

PMID- 16620329
TI  - Blood flow to the promontory in cochlear otosclerosis.
AB  - OBJECTIVE: To investigate Schwartze sign with measurements of blood flow to the
      promontory in patients with cochlear otosclerosis. DESIGN: Prospective clinical
      study. SETTING: Tertiary referral centre. PARTICIPANTS: Five patients with
      cochlear otosclerosis and five control subjects. Significant decalcification
      around the cochlea was observed by computed tomography (CT) in patients with
      cochlear otosclerosis. However, no recognizable lesion was observed at the oval
      window in two patients. One patient had mixed hearing loss and four patients had
      sensorineural hearing loss without an air-bone gap. MAIN OUTCOME MEASURES: The
      relationship between CT findings and the presence or absence of Schwartze sign
      was investigated. Blood flow to the promontory was measured through the tympanic
      membrane using laser speckle flowgraphy and laser Doppler flowmetry. RESULTS: The
      Schwartze sign correlated significantly with otosclerotic lesions invading the
      promontory. Patients with otosclerosis exhibited elevated and pulsating blood
      flow to the promontory with the Schwartze sign. CONCLUSIONS: Computed tomography
      demonstrated that cochlear otosclerosis can exist without the oval window lesion.
      Schwartze sign can be used as a sign of the otosclerotic invasion to the
      promontory. The reddening of the Schwartze sign is likely due to increased blood
      flow.

PMID- 16620330
TI  - Cochlear implant outcomes and quality of life in the elderly: Manchester
      experience over 13 years.
AB  - OBJECTIVES: To objectively evaluate the clinical and functional outcomes of
      cochlear implantation in an elderly population. DESIGN: Retrospective comparative
      study. SETTING: Neurotology unit at Manchester Royal Infirmary, a supraregional
      tertiary referral centre in collaboration with Adult Cochlear Implant Programme
      at The University of Manchester. PARTICIPANTS: All cochlear implant procedures
      (38) undertaken on post-lingually deafened elderly patients (age range at the
      time of implantation 65-80 years, n = 34) in the period from 1989 to 2002. MAIN
      OUTCOME MEASURES: Medical and surgical outcomes. Audiological performance
      outcomes for isolated words, words in sentences in quiet and noise. Functional
      outcome measures used are self-reported measures of the social, psychological and
      emotional aspects of quality of life, and the differences between expectations
      for functional outcomes and the realization of functional outcomes. They included
      expectation profiles, Glasgow Benefit inventory (GBI) and Glasgow Health Status
      Inventory Questionnaire (GHSI). RESULTS: There was statistically significant
      improvement post-implantation of both open and closed set test scores (P < 0.01).
      Eighty-two percentage of patients were completely satisfied with their cochlear
      implants. Patients judged that implantation restored half the loss of quality of
      life that they had experienced as a result of severe-profound deafness with a
      highly significant (P < 0.001) improvement in overall quality of life after
      implantation. The commonest post-operative observation was transient mild
      pyrexia. CONCLUSIONS: The age of a cochlear implant candidate should not be a
      factor in the candidacy decision-making process. The quality of life of our
      elderly recipients was significantly improved after cochlear implant.

PMID- 16620331
TI  - Reproducibility of volume measurements of vestibular schwannomas - a preliminary
      study.
AB  - OBJECTIVE: A preliminary study to investigate the intra-observer and inter
      observer variability of measurements of vestibular schwannoma volume using an
      area-tracing and linear dimension measurement method. DESIGN: Prospective blinded
      measurements by two observers (one a consultant and one a sub-specialty trainee
      in neuroradiology). SETTING: Ambulatory patients with known vestibular schwannoma
      attending a tertiary referral centre. PARTICIPANTS: Twenty-three patients with 26
      vestibular schwannomas aged 29-80 years old. MAIN OUTCOME MEASURE: Quantification
      of the variability in measured volume due to intra- and inter-observer
      measurement differences, expressed as reliability coefficients within which 95%
      of repeated measurements are calculated to lie from each other in relative
      percentage terms. RESULTS: For the linear measurement method, intraobserver
      variability was calculated to have a reliability coefficient of 65% and for
      interobserver variability this was 155%. For the area tracing method, the
      corresponding coefficients were 26% for intraobserver variability and 44% for
      interobserver variability. CONCLUSIONS: Volume measurements in vestibular
      schwannoma are variable even when the measurements are made by the same observer
      on identical images. The area tracing method, commonly regarded as the gold
      standard, is less variable than a linear method but still introduces more
      variability than commonly realized (for 95% of patients, repeated measurements by
      the same observer lie within around 25% of each other). Manual area tracing is
      not widely used in practice because it is time consuming and reliable automated
      methods are eagerly awaited.

PMID- 16620332
TI  - Total serum IgE and IgE antibodies specific to house dust mite found in two aged
      matched cohorts of children with and without otitis media with effusion.
AB  - OBJECTIVES: To determine whether otitis media with effusion (OME) is associated
      with elevated serum immunoglobulin E (IgE) and IgE specific for house dust mite.
      DESIGN: Forty-seven children who had evidence of bilateral OME, both
      otoscopically and on tympanometry, on two separate occasions, 3 months apart were
      admitted for ventilation tubes. Forty-eight children admitted for minor eye
      surgery who had otoscopically normal ears and no history of middle ear problems
      were used as controls. Bloods samples were taken under anaesthesia. Total IgE and
      IgE radioallergosorbent test (RAST) to house dust mite was measured by the
      Pharmacia Unicap 100 system. The results from the two groups were compared.
      SETTING: Birmingham Children's Hospital. PARTICIPANTS: Children between the ages
      of 3 and 10. Children with Down's syndrome, cleft lip and palate, ciliary
      abnormalities, known immunodeficiencies and cardiac abnormalities were excluded.
      MAIN OUTCOME MEASURES: Total IgE and RAST to house dust mite. A RAST of >0.35 was
      taken to be positive. RESULTS: There was no statistical difference between the
      control and study groups for the total IgE. Six children from both study and
      control groups had a raised house dust mite RAST. There was no difference in the
      levels between either group. CONCLUSIONS: Our findings indicate that there is no
      direct relationship between OME and biochemical evidence of allergy, specifically
      to house dust mite.

PMID- 16620333
TI  - A randomized controlled trial: is water better than a standard lubricant in
      nasendoscopy?
AB  - OBJECTIVES: Previous studies have shown that nasendoscopy is made easier with the
      use of lubrication at the expense of the quality of the view obtained, but had no
      effect on the discomfort or pain experienced by the patient. We set out to
      determine whether the advantages of lubrication with a standard lubricant (KY
      Jelly) could be achieved by using water, without incurring the same
      disadvantages. DESIGN: Single blind randomized controlled trial. SETTING:
      Outpatient Departments at two District General Hospitals. PARTICIPANTS: One
      hundred and fifty participants selected sequentially from patients requiring a
      nasendoscopy where the endoscope would be passed far enough to view the larynx.
      Patients requiring topical anaesthetic were excluded. METHODS: Patients were
      randomly assigned to have either water or standard lubricant applied to the
      nasendosope prior to nasendoscopy. Levels of pain experienced by the patient were
      recorded on a visual analogue score as well as visual analogue scores from the
      clinician for the levels of difficulty in passing the endoscope. All participants
      who were entered the study completed the study. Endoscopy was performed by all
      grades of medical staff. MAIN OUTCOME MEASURES: Levels of pain experienced by the
      participants were assessed by a visual analogue scale. Difficulty of passing the
      scope was indicated by the endoscopist using a visual analogue scale, as was the
      quality of image obtained. RESULTS: Endoscopists found the insertion of the
      endoscope was easier and the image better when water was used rather than KY
      Jelly. There was no significant difference in reported in levels of pain
      experienced by the patient. CONCLUSION: Although the use of water as a lubricant
      during nasendoscopy confers no additional benefit in term of the levels of pain
      suffered by patients during the procedure, it makes the insertion of the
      endoscope easier and provides a better quality image than standard lubrication.

PMID- 16620334
TI  - Randomized-controlled study comparing post-operative pain between coblation
      palatoplasty and laser palatoplasty.
AB  - OBJECTIVES: This study aimed to evaluate differences in post-operative pain
      comparing KTP laser-assisted uvulopalatoplasty without tonsillectomy (LAUP) with
      a new described surgical method: coblation uvulopalatoplasty with tonsillectomy
      (CP). We also evaluate the impact of each surgical technique in reduction of
      snoring loudness. MATERIAL AND METHODS: Single blind randomized-controlled trial.
      From a population of 41 consecutive patients on the waiting list for
      uvulopalatoplasty for simple snoring, the study group was reduced to 17 CP and 13
      LAUP. Post-operative pain and reduction of snoring loudness were recorded using
      visual analogue scales (VAS) during the first 15 post-operative days. Post
      operative snoring loudness was documented for 1-year period. RESULTS: Both groups
      had similar post-operative pain during the first seven post-operative days. A
      statistically significant reduction in post-operative pain was observed in the CP
      group after day 8, and maintained until the end of the study. Reduction of
      snoring loudness was significant in both groups, but no differences were observed
      between them. DISCUSSION: Coblation uvulopalatoplasty compared with LAUP
      demonstrates a reduction in post-operative pain, significant after the first post
      operative week. The collateral thermal injury caused by laser is responsible for
      the slow-healing rate and maintained post-operative pain. Coblation dissociates
      tissue at lower temperatures with minimal collateral thermal injury and
      consequently faster and less painful recovery. Both surgical procedures have
      significant and similar reduction in snoring loudness. CONCLUSIONS: Both methods
      are adequate treatment options for snoring. The less painful recovery in CP
      promotes this surgical technique as our preferred choice for palate surgery.

PMID- 16620335
TI  - Prognostic value of electroneurography in Bell's palsy and Ramsay-Hunt's
      syndrome.
AB  - OBJECTIVES: This study evaluated the accuracy of electroneurography to predict
      the prognosis of Bell's palsy and Ramsay-Hunt's syndrome. DESIGN: A
      retrospective, institutional review board-approved study. SETTING: A secondary
      referral and a university-based centre. PARTICIPANTS: The patients had been
      treated for a sudden onset unilateral facial paralysis over the past 10 years
      (1994-2004). This retrospective study included only those patients who had been
      followed up for at least 3 months or if they had reached a complete recovery
      before then. MAIN OUTCOMES MEASURES: House-Backmann grade versus
      electroneurography value. RESULTS: The recovery rates to House-Brackmann grade II
      or better were 95% in those with Bell's palsy and 84% in those with herpes zoster
      oticus. The electroneurography value of the recovery and non-recovery groups from
      those with either Bell's palsy or herpes zoster oticus was similar. The logistic
      regression model between the electroneurography values and the probability of
      recovery showed no correlation in those with Bell's palsy or with herpes zoster
      oticus. This study did not identify the proper electroneurography value that had
      enough appropriate sensitivity and specificity to predict the prognosis of
      paralysis accurately in Bell's palsy or in herpes zoster oticus patients.
      CONCLUSION: Electroneurography performed between day 7 and 10 for Bell's palsy or
      day 10 and 14 for herpes zoster oticus does not provide accurate information on
      the prognosis or recovery rate of the facial paralysis.

PMID- 16620338
TI  - How we do it: a new 'one stop' ear wick.
AB  - In some practices, otitis externa is treated with ear wick and patient is asked
      to remove it independently without re-attending clinic. * Although this method
      reduces workload on aural care services, it can be unhygienic and difficult to
      perform. * We propose a new design whereby the wick is tied to a string to
      facilitate its later removal. * Out of 18 patients treated with this method, only
      4 opted to re-attend for further aural care.

PMID- 16620339
TI  - How we do it: technical note: endoscopic removal of cerumen.
AB  - * Syringing of ears to remove cerumen is losing favour in primary care owing to
      the fact that it is carried out 'blind' and that the potential exists for serious
      complications. * Dewaxing under direct vision is difficult without a microscope.
      * A technique is described where wax is removed under direct vision using a rigid
      endoscope in conjunction with a Jobson-Horne probe and St Bartholomew's wax hook.
      * This is a relatively inexpensive technique that could be introduced to primary
      care practitioners or to ENT surgeons who do not have easy access to an operating
      microscope in the outpatient department.

PMID- 16620340
TI  - How we do it: coblation tonsillectomy complication rates from a single ENT
      department compared with the National Prospective Tonsillectomy Audit.
AB  - Coblation tonsillectomy is a relatively new technique, the results of which need
      auditing within practising units, to justify its continued usage. * The National
      Prospective Tonsillectomy Audit provides an excellent source of data for
      individual units to compare their results to. * This retrospective audit of 391
      coblation tonsillectomies shows that our units haemorrhage and return to theatre
      rates are similar to the National rates for cold steel & ties data. * Resolution
      of training issues and patient selection may lead to increased use of this
      technique.

PMID- 16620341
TI  - How we do it: surgery should be considered equally with I131 and thionamide
      treatment as first-line therapy for thyrotoxicosis.
AB  - Radioiodine and thionamide treatment are the most frequently used treatment
      modalities for thyrotoxicosis in Europe and North America with surgery being
      reserved for selected cases. * In our clinic patients were offered all three
      modalities via simultaneous interview with an endocrinologist and a surgeon, with
      international risk benefit data for radioiodine and thionamide therapy, and local
      risk benefit data for total thyroidectomy provided. * When given the choice, at
      least 15% of patients opted for total thyroidectomy over the other modalities. *
      In our series of 100 consecutive surgical patients there was a 4% malignancy
      rate. * Total thyroidectomy should be offered equally, with radioiodine and
      thionamide treatment, as a first line treatment modality in the management of
      thyrotoxicosis.

PMID- 16620342
TI  - The Bradford grommet trainer.

PMID- 16620343
TI  - Dilatation of tracheostomal stenosis using uterine dilators.

PMID- 16620344
TI  - The need to include BIPP reactions in routine consent.

PMID- 16620346
TI  - Primary angioplasty in acute myocardial infarction - the preferred option, but
      time is of the essence.

PMID- 16620347
TI  - When natural is not harmless.

PMID- 16620348
TI  - Barriers to treating depression in primary care.

PMID- 16620349
TI  - Management and outcomes of acute coronary syndrome with minimal myocardial
      necrosis: analysis of a large prospective registry from a non-interventional
      centre.
AB  - The aim of this study was to assess the clinical risk of minimal myonecrosis
      below the cut-off for acute myocardial infarction (MI) in comparison with other
      grades of acute coronary syndrome (ACS). One-thousand four hundred and sixty
      seven consecutive patients with ACS admitted between May 2001 and April 2002 were
      studied in a non-interventional centre. Patients were divided into unstable
      angina (UA) (cTnT < 0.01 microg/l), non-ST elevation ACS with minimal myonecrosis
      (0.01 <or= cTnT < 0.1 microg/l), non-ST elevation MI (NSTEMI) (cTnT >or= 0.1
      microg/L) and ST elevation myocardial infarction (STEMI). UA (n = 638) was
      associated with the fewest events at 6 months (2% cardiac death or MI). Patients
      with any myonecrosis (n = 829) had worse outcomes (6-month cardiac death or MI
      18.3-23.3%). Compared with ACS patients with minimal myonecrosis, UA patients
      were at significantly lower risk (OR 0.21, 95% CI 0.12-0.45, p < 0.001), NSTEMI
      patients were at similar risk (OR 1.45, 95% CI 0.89-2.35, p = 0.13), and STEMI
      patients were at higher risk (OR 2.12 95% CI 1.26-3.85, p = 0.008) in adjusted
      analyses. Nearly 85% of cardiac deaths occurred within 6 months. The risk of
      adverse events was higher among patients managed by non-cardiologists (OR 1.66,
      95% CI 1-2.75, p = 0.049). Patients with non-ST elevation ACS and minimal
      myonecrosis are a high-risk group more comparable with NSTEMI and clearly
      distinguishable from patients with UA.

PMID- 16620350
TI  - A placebo-controlled comparison of the efficacy and tolerability of candesartan
      cilexetil, 8 mg, and losartan, 50 mg, as monotherapy in patients with essential
      hypertension, using 36-h ambulatory blood pressure monitoring.
AB  - This double-blind, randomised, controlled study compared the efficacy of
      candesartan cilexetil 8 mg (n = 87) and losartan 50 mg (n = 89), once daily for 6
      weeks, relative to placebo (n = 80) in patients with mild-to-moderate essential
      hypertension (diastolic blood pressure (DBP): 95-115 mmHg). Ambulatory BP
      measurements were done every 15 min over 36 h. At the end of the 6-week
      treatment, the mean change in DBP between the baseline and the 0-24-h period
      after the last dose of study medication was greater in patients receiving
      candesartan cilexetil 8 mg (-7.3 mmHg +/- 6.9 mmHg) compared with losartan 50 mg
      (-5.1 mmHg +/- 4.9 mmHg) (p < 0.05) or placebo (0.3 mmHg +/- 6.5 mmHg) (p <
      0.001). The mean change in systolic BP (SBP) during this time was greater in
      patients receiving candesartan cilexetil 8 mg (-10.8 mmHg +/- 11.3 mmHg), or
      losartan 50 mg (-8.8 mmHg +/- 8.9 mmHg) than placebo (1.2 mmHg +/- 9.9 mmHg) (p <
      0.001). Candesartan cilexetil 8 mg was associated with a greater reduction in DBP
      and SBP, relative to placebo, when compared with losartan 50 mg, during both
      daytime and night-time, and between 12 and 24 h after dosing (p < 0.001). Both
      active treatments were well tolerated. In patients with mild-to-moderate
      essential hypertension, candesartan cilexetil 8 mg therefore had greater, more
      consistent antihypertensive efficacy throughout the day and the night, and long
      lasting efficacy after the last dose, compared with losartan 50 mg. This greater
      efficacy is maintained with an excellent tolerability associated with members of
      the angiotensin Il type 1-receptor blocker class.

PMID- 16620352
TI  - Magnetic resonance imaging in the quantitative assessment of gouty tophi.
AB  - Measurements of tophus size can be important in monitoring the course of gout
      therapy, as tophus resolution is proposed as one measure of success of treatment.
      This multicentre study assessed the intra- and interreader reproducibility of
      quantitative tophus volume measurements from magnetic resonance images (MRI) in
      subjects with palpable gouty tophi. Subjects first underwent radiographic imaging
      of a selected tophus followed by MRI before and at <or=5, 10 and 20-min after
      gadolinium administration. After choosing optimal parameters, subjects underwent
      pre- and postgadolinium-enhanced MRIs of a selected tophus on two occasions
      separated by 5-10 days. Unenhanced spin-echo images provided satisfactory tophi
      images and were less subject to interfering artefacts than gadolinium-enhanced
      gradient-echo images. Intrareader reproducibility was excellent, with no
      statistically significant difference in mean tophus volume between visits (mean
      difference - 0.05 +/- 0.97 cm3). A small but statistically significant difference
      in interreader mean tophus volume was detected (mean difference 0.89 +/- 2.05
      cm3; p < 0.05). MRI can quantify tophus size in gout and deserves further
      comparison with other techniques for tophus size monitoring in assessing effects
      of gout therapy.

PMID- 16620351
TI  - Treating the acute stroke patient as an emergency: current practices and future
      opportunities.
AB  - Developments in acute stroke therapy have followed advances in the understanding
      of the evolving pathophysiology in both ischaemic stroke and intracerebral
      haemorrhage (ICH). In ischaemic stroke, rapid reperfusion of the ischaemic
      penumbra with thrombolysis within 3 h of symptom onset is of proven benefit, but
      few patients currently receive therapy, mainly due to the short-time window and
      lack of stroke expertise. In ICH, a recent study indicated that a haemostatic
      agent can limit ongoing bleeding and improve outcomes when administered within 4
      h of stroke onset. These advances in acute stroke therapy underlie the concept
      that 'time is brain' and that urgent intervention can limit cerebral damage.
      Neuroprotective therapy could offer the prospect of a greater proportion of
      stroke patients receiving treatment, potentially before imaging and even in the
      ambulance setting. Virtually all stroke patients would benefit from receiving
      multidisciplinary care in acute stroke units.

PMID- 16620353
TI  - Evidence of tachyphylaxis associated with salmeterol treatment of chronic
      obstructive pulmonary disease patients.
AB  - Bronchodilator therapy is lifelong mandatory for chronic obstructive pulmonary
      disease patients. There is evidence of loss of bronchodilator effectiveness over
      time with beta2-agonists but not with anticholinergics. The aim of this study was
      to examine the development of tachyphylaxis to the long-acting beta2-agonist
      salmeterol using as a control therapeutic regimen the combination of ipratropium
      bromide and salbutamol sulphate. Fifty-six subjects participated in a 20-week,
      crossover randomised clinical trial. The parameters forced expiratory volume at 1
      s (FEV1), peak expiratory flow rate (PEFR) and FEV1/forced vital capacity were
      measured via spirometry and the parameters triangle DeltaFEV1%pre, triangle
      DeltaPEFR%pre and triangle DeltaAUC(0-2 h) were calculated. FEV1 increased
      significantly after two weeks of treatment with the combination treatment but not
      with the salmeterol. The observed diminished increase could be attributed to the
      development of tolerance to the long acting beta2-agonist. Salmeterol seems to be
      an effective bronchodilator, however, its duration of action over time and its
      peak effect might be subject to tachyphylaxis.

PMID- 16620354
TI  - Multifactorial approach and adherence to prescribed oral medications in patients
      with type 2 diabetes.
AB  - The aims of this study were to assess adherence to oral
      hypoglycaemic/cardiovascular drugs and determine non-adherence predictors in type
      2 diabetes patients. It was designed as a population-based cross-sectional study
      in which 90 patients from a primary care setting were studied. Pill count and
      self-report methods were used to measure adherence. Logistic regression analysis
      was performed to predict factors related to non-adherence. Adequate adherence to
      all drugs was found in 29 patients (35.4%; 95% confidence interval (CI) 25.0
      45.7). Variables associated with non-adherence were HbA1c odds ratio (OR) 2.32
      (95% CI: 1.09-4.95), systolic blood pressure OR 1.68 (95% CI: 1.08-2.62), total
      cholesterol OR 1.34 (95% CI: 1.08-1.66), number of pills OR 1.80 (95% CI: 1.26
      2.55) and duration of disease OR 0.44 (CI 95%: 0.24-0.83). In conclusion, one in
      three patients had adequate adherence. Factors associated with non-adherence were
      duration of disease, complexity of drug regimen and inadequate control of
      cardiovascular risk factors.

PMID- 16620355
TI  - Subcutaneous lispro and intravenous regular insulin treatments are equally
      effective and safe for the treatment of mild and moderate diabetic ketoacidosis
      in adult patients.
AB  - In this prospective, randomised, open trial, we wanted to evaluate the efficacy
      and safety of hourly subcutaneous (SC) insulin lispro administration in the
      treatment of diabetic ketoacidosis (DKA) in comparison with intravenous (IV)
      regular insulin treatment. Twenty patients were enrolled in the study. The
      patients were randomly assigned into two groups. Following a bolus injection of
      0.15 U/kg IV regular insulin, group L received half of this dose as hourly SC
      insulin lispro while group R was treated conventionally with IV regular insulin
      infusion. At the end of treatment period, time that needed for normalisation of
      serum glucose, beta-hydroxybutyrate, blood pH and urine ketone levels were not
      different in groups L and R. There was no mortality or serious side effects in
      both groups. In this study, we revealed that treatment of mild and moderate DKA
      with SC insulin lispro is equally effective and safe in comparison with IV
      regular insulin.

PMID- 16620356
TI  - Vetted access to day case hand surgery.
AB  - This prospective study was undertaken in the day surgery unit of Monklands
      Hospital, Airdrie. The consultant hand surgeon screened all general practitioner
      referrals between September 1998 and July 2002, and suitable patients referred
      for minor hand procedures were listed directly on to the day-case waiting list
      without an initial review in outpatient department. The main end points in this
      study were accuracy of diagnosis, the appropriateness of surgical treatment plan,
      patient acceptability and the impact of direct listing on waiting times and
      attendance. There was agreement in clinical diagnosis in 92%, and the choice of
      treatment plan was judged to be appropriate in 96% cases. The overall patient
      acceptability was 90%. This one-visit system not only cuts down on the patients
      waiting time from initial referral up to surgery but also reduces the number of
      hospital visits for the patients.

PMID- 16620357
TI  - What are the barriers faced by general practitioners in treating depression and
      anxiety in Hong Kong?
AB  - Barriers faced by general practitioners in Hong Kong to manage patients with
      depression and anxiety disorders and their association with postgraduate
      qualification in family medicine were studied. Postal questionnaires were sent to
      179 family medicine tutors affiliated with a university in Hong Kong with a
      response rate of 64.2%. 'Too time consuming' was the largest barrier for these
      physicians in treating patients with depression and anxiety. General
      practitioners without higher qualifications in family medicine were significantly
      more likely to report 'lack of confidence', 'lack of experience' and 'lack of
      supporting service' as being the barriers in treating patients with depression
      and anxiety. Our results showed that time constraint is an important barrier for
      general practitioners in managing patients with depression and anxiety in Hong
      Kong. Having a higher qualification in family medicine may reduce the barriers of
      having lack of confidence and experience in these physicians.

PMID- 16620358
TI  - FIELDS of dreams, fields of tears: a perspective on the fibrate trials.
AB  - Endpoint studies have been performed with fibrates in coronary heart disease
      since 1971. The results have been confusing - starting with initial benefits in
      small studies, but contradicted by either minimal benefits in the Coronary Drug
      Project or adverse noncardiovascular (non-CV) effects in the World Health
      Organization Clofibrate Study. Fibrates returned for patients with low HDL-C and
      low LDL-C after a 25% event reduction were seen in the Veterans Affairs HDL
      Intervention Trial. The greater prominence ascribed to the lipid triad of the
      metabolic syndrome and the increasing prevalence of diabetes increased the
      topicality of fibrates given their main action of converting small dense to light
      buoyant LDL. The Fenofibrate Intervention in Event Lowering in Diabetes (FIELD)
      Study has carried on the tradition. Fenofibrate therapy in 9795 patients
      comprising a mixed low-risk primary and a medium-risk secondary prevention cohort
      resulted in an 11% reduction in coronary events (p = 0.16), a similar but
      significant reduction in CV events (p = 0.04; number needed to treat = 70). The
      benefits were concentrated in primary prevention and on nonfatal myocardial
      events, but the study was confounded by asymmetrical statin drop-in due to the
      LDL-C-lowering effect of fenofibrate. Safety was generally good, including in
      combination with statins, but old concerns about sudden death, pancreatitis and
      venous thrombosis returned. Unexpected benefits were seen with fenofibrate on
      microvascular endpoints including microalbuminuria and retinopathy. Fenofibrate
      is a reasonable second-line therapy for dyslipidaemia in diabetes and safe in
      combination therapy. Its benefits on microvascular disease and in combination
      therapy require further confirmation.

PMID- 16620359
TI  - Controlling invasive pneumococcal disease: is vaccination of at-risk groups
      sufficient?
AB  - Risk factors for invasive pneumococcal disease (IPD) include young and old age,
      comorbidities (such as splenic dysfunction, immunodeficiencies, chronic renal
      disease, chronic heart or lung disease or cerebral spinal fluid leak), crowded
      environments or poor socioeconomic conditions. Universal use of the 7-valent
      pneumococcal conjugate (7vPncCRM) vaccine for infants and young children has led
      to significant decreases in IPD in the vaccinated population (direct protection),
      and there has also been a decrease in the incidence of IPD among the
      nonvaccinated population (indirect immunity; herd protection). While 7vPncCRM
      vaccine is administered universally to children in USA, many countries of the
      European Union have chosen to target children with comorbidities. This review
      aims to highlight individual risk factors for IPD, describe studies that
      evaluated pneumococcal conjugate vaccines in at-risk groups and estimate the
      proportion of at-risk children who may have been vaccinated in the European Union
      since the 7vPncCRM vaccine was introduced, using UK as an example. Although
      immunisation targeting only children with comorbidities may achieve satisfactory
      results for a few, many otherwise healthy children at risk simply because of
      their age will be neglected, and herd protection might not be established.

PMID- 16620360
TI  - Macroprolactin: what is it and what is its importance?
AB  - Monomeric prolactin (PRL) of molecular weight 23 kDa constitutes up to 95% of
      adult serum PRL. Macroprolactin is a large antigen-antibody complex of molecular
      weight greater than 100 kDa and constitutes less than 1% of circulating PRL.
      Thus, in most cases, hyperprolactinaemia is usually a result of high levels of
      monomeric PRL, which may be due to excess production as with a prolactinoma or
      due to disinhibition by compression of the pituitary stalk. Nevertheless, it must
      be noted that macroprolactinaemia may be a cause of hyperprolactinaemia in some
      individuals, which may have no association with any pathology. The presence of
      macroprolactin should always be suspected when a patient's clinical history
      and/or radiological data are incompatible with his/her PRL value. Thus, it may be
      useful to screen all patients with high sera PRL levels in order to prevent
      unnecessary investigations into the cause for hyperprolactinaemia. This has
      recently been facilitated with the advent of simple laboratory tests such as the
      polyethyleneglycol precipitation method, although gel filtration chromatography
      remains the gold standard. It is hoped that macroprolactinaemia is included in
      the differential diagnosis of hyperprolactinaemia.

PMID- 16620362
TI  - Breast reconstruction.
AB  - The majority of women who are undergoing mastectomy can also have breast
      reconstruction. In most breast units, implants and latissimus dorsi flaps can be
      performed. The more sophisticated transverse rectus abdominis myocutaneous (TRAM)
      flap-based reconstructions are generally performed by plastic surgeons so that
      there may be logistic problems in using these techniques for immediate
      reconstruction. Decisions on technique will also depend on the patient's build
      and co-existing medical conditions together with the likelihood of need for
      postoperative radiotherapy as part of the primary local treatment.

PMID- 16620361
TI  - New perspective in the management of neuroendocrine differentiation in prostate
      adenocarcinoma.
AB  - In this review, we will present some of the information that is known about
      neuroendocrine (NE) cells and differentiation in the prostate. We will then
      speculate on the potential role that NE differentiation in prostate carcinoma may
      play and how this differentiation may be clinically analysed and treated. The
      androgen-independent growth of prostate cancer can be caused by different
      mechanisms; one of these is receptor-specific paracrine or autocrine growth
      modulation of human prostatic cancer cells by neuropeptides secreted by NE cells.
      Our results affirm that different methods of androgen deprivation can influence
      the serum chromogranin A (CgA) levels to different extents in prostate cancer. In
      particular, bicalutamide produces a significantly lower increase in serum CgA
      compared with castration therapy. In the light of other evidence that supports a
      significant relationship between serum CgA levels, tissue CgA expression and NE
      activity, we hypothesise that bicalutamide may reduce the risk of NE cell
      hyperactivation in prostate cancer. It is important to determine whether
      increases in CgA levels and NE cell activation are associated with progression
      towards hormone-independent prostate cancer. We recently proposed as therapy of
      NE activation in hormone-independent prostate cancer, a combination of oestrogens
      and somatostatin analogues. The combination of ethinyl estradiol and lanreotide
      had a favourable toxicity profile, offered objective and symptomatic responses in
      patients with limited treatment options and refractoriness to conventional
      hormonal therapy strategies and, in particular, offered a median overall survival
      that was superior to the 10-month median survival in patients with hormone
      refractory disease. This combination therapy also sustains the novel concept in
      cancer treatment in which therapies may target not only cancer cells but also its
      microenvironment in combination, which can confer protection from apoptosis.

PMID- 16620363
TI  - Sitaxsentan: an endothelin-A receptor antagonist for the treatment of pulmonary
      arterial hypertension.
AB  - Endothelin (ET-1) is a potent vasoconstrictor and smooth muscle mitogen that
      mediates its effects through activation of ET-A and ET-B receptors. Pulmonary
      arterial hypertension (PAH) encompasses a heterogeneous group of disorders
      characterised by inappropriate overactivation of the ET system. There is clear
      evidence that strategies that block both ET receptors are associated with
      clinical improvement in PAH. However, there are theoretical physiological
      advantages to treatments that specifically inhibit only the ET-A receptor.
      Sitaxsentan is an orally active selective ET-A receptor antagonist that in recent
      clinical trials has demonstrated improvements in exercise capacity, functional
      class and haemodynamics in PAH patients with modified New York Heart Association
      class II, III and IV symptoms.

PMID- 16620365
TI  - Anticholinergic syndrome due to 'Devil's herb': when risks come from the ancient
      time.
AB  - We describe a case of Mandragora autumnalis poisoning which occurred in a 72-year
      old female patient who had eaten the venenous M. Autumnalis, picked near her
      home, mistaking it for the edible Borago Officinalis. M. Autumnalis is a
      solanaceous plant, common in the Sicilian countryside, which contains a variable
      concentration of solanum alkaloids, causing gastrointestinal irritation, and
      tropane alkaloids, with anticholinergic properties. Unluckily, M. Autumnalis is
      often mistaken for the edible B. Officinalis, likewise widespread in Sicilian
      countryside. The diagnosis of Mandragora poisoning was made on the basis of
      clinical symptoms and signs of anticholinergic syndrome associated with a history
      of vegetable meal of uncontrolled origin, moreover analysing the vegetable
      obtained from gastric lavage. Decontamination and symptomatic treatment were
      useful in our patient to control acute poisoning.

PMID- 16620364
TI  - Tolerability and safety of fluvoxamine and other antidepressants.
AB  - Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and
      the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in
      treatment for depression. The highly specific actions of SSRIs of enhancing
      serotonergic neurotransmission appears to explain their benefit, while lack of
      direct actions on other neurotransmitter systems is responsible for their
      superior safety profile compared with tricyclic antidepressants. Although SSRIs
      (and venlafaxine) have similar adverse effects, certain differences are emerging.
      Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs
      have a cardiovascular safety profile superior to that of tricyclic
      antidepressants for patients with cardiovascular disease; fluvoxamine is safe in
      patients with cardiovascular disease and in the elderly. A discontinuation
      syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than
      tricyclic antidepressants in overdose, and there is no conclusive evidence to
      suggest that they are associated with an increased risk of suicide. Although the
      literature suggests that there are no clinically significant differences in
      efficacy amongst SSRIs, treatment decisions need to be based on considerations
      such as patient acceptability, response history and toxicity.

PMID- 16620366
TI  - Inflammation in atrial fibrillation and atherosclerosis: pearls and pitfalls in
      the theorising process.

PMID- 16620368
TI  - Do the National Institute of Clinical Excellence guidelines apply to 'real world'
      use of Abciximab in percutaneous coronary intervention in a teaching hospital
      setting?

PMID- 16620369
TI  - Sildenafil citrate use and the incidence of nonarteritic anterior ischemic optic
      neuropathy.
AB  - Nonarteritic anterior ischemic optic neuropathy (NAION) has been reported rarely
      in men after taking sildenafil or other phosphodiesterase 5 inhibitors for
      erectile dysfunction (ED). The incidence of NAION in men receiving sildenafil
      treatment for ED was estimated using pooled safety data from global clinical
      trials and European observational studies. Based on clinical trial data in more
      than 13,000 men and on more than 35,000 patient-years of observation in
      epidemiologic studies, we estimated an incidence of 2.8 cases of NAION per
      100,000 patient-years of sildenafil exposure. This is similar to estimates
      reported in general US population samples (2.52 and 11.8 cases per 100,000 men
      aged >or=50 years). The data cited herein do not suggest an increased incidence
      of NAION in men who took sildenafil for ED.

PMID- 16620370
TI  - Malaria pigment paralyzes dendritic cells.
AB  - The capacity of malarial infection to suppress the patient's immune responses
      both to the parasite and to other antigens has long puzzled researchers. A prime
      suspect, the parasite-produced pigment hemozoin, has now been clearly shown to
      mediate immunosuppression by inhibiting dendritic cell activity.

PMID- 16620371
TI  - Pro-con debate: steroid use in ACTH non-responsive septic shock patients with
      high baseline cortisol levels.
AB  - Steroid use in critically ill, vasopressor-dependant, septic patients has gained
      increased acceptance in recent years with the publication of encouraging data.
      However, with renewed interest and/or attention comes increased debate and
      analysis. As a result, it is not surprising to find that there is still
      significant controversy with regards to the role of steroids in many patients. In
      this article, two expert groups debate the role of steroid use in a septic shock
      patient with arguably no clear evidence of adrenal insufficiency.

PMID- 16620372
TI  - Local public health workers' perceptions toward responding to an influenza
      pandemic.
AB  - BACKGROUND: Current national preparedness plans require local health departments
      to play an integral role in responding to an influenza pandemic, a major public
      health threat that the World Health Organization has described as "inevitable and
      possibly imminent". To understand local public health workers' perceptions toward
      pandemic influenza response, we surveyed 308 employees at three health
      departments in Maryland from March-July 2005, on factors that may influence their
      ability and willingness to report to duty in such an event. RESULTS: The data
      suggest that nearly half of the local health department workers are likely not to
      report to duty during a pandemic. The stated likelihood of reporting to duty was
      significantly greater for clinical (Multivariate OR: 2.5; CI 1.3-4.7) than
      technical and support staff, and perception of the importance of one's role in
      the agency's overall response was the single most influential factor associated
      with willingness to report (Multivariate OR: 9.5; CI 4.6-19.9). CONCLUSION: The
      perceived risk among public health workers was shown to be associated with
      several factors peripheral to the actual hazard of this event. These risk
      perception modifiers and the knowledge gaps identified serve as barriers to
      pandemic influenza response and must be specifically addressed to enable
      effective local public health response to this significant threat.

PMID- 16620373
TI  - Carotenoid dynamics in Atlantic salmon.
AB  - BACKGROUND: Carotenoids are pigment molecules produced mainly in plants and
      heavily exploited by a wide range of organisms higher up in the food-chain. The
      fundamental processes regulating how carotenoids are absorbed and metabolized in
      vertebrates are still not fully understood. We try to further this understanding
      here by presenting a dynamic ODE (ordinary differential equation) model to
      describe and analyse the uptake, deposition, and utilization of a carotenoid at
      the whole-organism level. The model focuses on the pigment astaxanthin in
      Atlantic salmon because of the commercial importance of understanding carotenoid
      dynamics in this species, and because deposition of carotenoids in the flesh is
      likely to play an important life history role in anadromous salmonids. RESULTS:
      The model is capable of mimicking feed experiments analyzing astaxanthin uptake
      and retention over short and long time periods (hours, days and years) under
      various conditions. A sensitivity analysis of the model provides information on
      where to look for possible genetic determinants underlying the observed
      phenotypic variation in muscle carotenoid retention. Finally, the model framework
      is used to predict that a specific regulatory system controlling the release of
      astaxanthin from the muscle is not likely to exist, and that the release of the
      pigment into the blood is instead caused by the androgen-initiated autolytic
      degradation of the muscle in the sexually mature salmon. CONCLUSION: The results
      show that a dynamic model describing a complex trait can be instrumental in the
      early stages of a project trying to uncover underlying determinants. The model
      provides a heuristic basis for an experimental research programme, as well as
      defining a scaffold for modelling carotenoid dynamics in mammalian systems.

PMID- 16620375
TI  - Fast rate of evolution in alternatively spliced coding regions of mammalian
      genes.
AB  - BACKGROUND: At least half of mammalian genes are alternatively spliced.
      Alternative isoforms are often genome-specific and it has been suggested that
      alternative splicing is one of the major mechanisms for generating protein
      diversity in the course of evolution. Another way of looking at alternative
      splicing is to consider sequence evolution of constitutive and alternative
      regions of protein-coding genes. Indeed, it turns out that constitutive and
      alternative regions evolve in different ways. RESULTS: A set of 3029 orthologous
      pairs of human and mouse alternatively spliced genes was considered. The rate of
      nonsynonymous substitutions (dN), the rate of synonymous substitutions (dS), and
      their ratio (omega = dN/dS) appear to be significantly higher in alternatively
      spliced coding regions compared to constitutive regions. When N-terminal,
      internal and C-terminal alternatives are analysed separately, C-terminal
      alternatives appear to make the main contribution to the observed difference. The
      effects become even more pronounced in a subset of fast evolving genes.
      CONCLUSION: These results provide evidence of weaker purifying selection and/or
      stronger positive selection in alternative regions and thus one more confirmation
      of accelerated evolution in alternative regions. This study corroborates the
      theory that alternative splicing serves as a testing ground for molecular
      evolution.

PMID- 16620377
TI  - Frontal mucocele with an accompanying orbital abscess mimicking a fronto-orbital
      mucocele: case report.
AB  - BACKGROUND: Mucoceles are slowly expanding cystic lesions with respiratory
      epithelium containing mucus most commonly affecting the frontal and ethmoidal
      sinuses. They are caused by obstruction of sinus ostium. Mucoceles exert pressure
      on the bony boundaries and due to the proximity to the brain and orbit extension
      to these areas are common. CASE PRESENTATION: A case of a frontal mucocele with
      an accompanying orbital abscess mimicking a fronto-orbital mucocele is reported.
      A 77 year old female patient suffering from left sided proptosis and pain around
      the left eye was admitted to our department. She had a history of left frontal
      sinus mucocele one year ago that was offered an osteoplastic frontal sinus
      surgery that the patient refused. Patient had limitation of eye movements.
      Fundoscopic examination revealed a minimal papilledema. Coronal computerized
      tomography and orbital magnetic resonance imaging showed a frontal mucocele with
      suspicious erosion of the orbital roof and a superiorly localized extraconal mass
      displacing the orbit lateroinferiorly. Frontal and orbital masses had similar
      intensities. Thus surgery was planned for a fronto-orbital mucocele. During
      surgery no defect was found on the orbital roof. Frontal mucocele and orbital
      cystic mass was removed separately. Pathological examination showed a frontal
      mucocele and an orbital abscess wall. Postoperatively eye movements returned to
      normal and papilledema resolved. CONCLUSION: Fronto-orbital mucoceles are
      commonly encountered pathologies, but frontal mucocele with an orbital abscess is
      a rarely seen and should be kept in mind because their treatments differ.

PMID- 16620374
TI  - Comparative genomics of the syndecans defines an ancestral genomic context
      associated with matrilins in vertebrates.
AB  - BACKGROUND: The syndecans are the major family of transmembrane proteoglycans in
      animals and are known for multiple roles in cell interactions and growth factor
      signalling during development, inflammatory response, wound-repair and
      tumorigenesis. Although syndecans have been cloned from several invertebrate and
      vertebrate species, the extent of conservation of the family across the animal
      kingdom is unknown and there are gaps in our knowledge of chordate syndecans.
      Here, we develop a new level of knowledge for the whole syndecan family, by
      combining molecular phylogeny of syndecan protein sequences with analysis of the
      genomic contexts of syndecan genes in multiple vertebrate organisms. RESULTS: We
      identified syndecan-encoding sequences in representative Cnidaria and throughout
      the Bilateria. The C1 and C2 regions of the cytoplasmic domain are highly
      conserved throughout the animal kingdom. We identified in the variable region a
      universally-conserved leucine residue and a tyrosine residue that is conserved
      throughout the Bilateria. Of all the genomes examined, only tetrapod and fish
      genomes encode multiple syndecans. No syndecan-1 was identified in fish. The
      genomic context of each vertebrate syndecan gene is syntenic between human, mouse
      and chicken, and this conservation clearly extends to syndecan-2 and -3 in T.
      nigroviridis. In addition, tetrapod syndecans were found to be encoded from
      paralogous chromosomal regions that also contain the four members of the matrilin
      family. Whereas the matrilin-3 and syndecan-1 genes are adjacent in tetrapods,
      this chromosomal region appears to have undergone extensive lineage-specific
      rearrangements in fish. CONCLUSION: Throughout the animal kingdom, syndecan
      extracellular domains have undergone rapid change and elements of the cytoplasmic
      domains have been very conserved. The four syndecan genes of vertebrates are
      syntenic across tetrapods, and synteny of the syndecan-2 and -3 genes is apparent
      between tetrapods and fish. In vertebrates, each of the four family members are
      encoded from paralogous genomic regions in which members of the matrilin family
      are also syntenic between tetrapods and fish. This genomic organization appears
      to have been set up after the divergence of urochordates (Ciona) and vertebrates.
      The syndecan-1 gene appears to have been lost relatively early in the fish
      lineage. These conclusions provide the basis for a new model of syndecan
      evolution in vertebrates and a new perspective for analyzing the roles of
      syndecans in cells and whole organisms.

PMID- 16620376
TI  - Significance of somatic mutations and content alteration of mitochondrial DNA in
      esophageal cancer.
AB  - BACKGROUND: The roles of mitochondria in energy metabolism, the generation of
      ROS, aging, and the initiation of apoptosis have implicated their importance in
      tumorigenesis. In this study we aim to establish the mutation spectrum and to
      understand the role of somatic mtDNA mutations in esophageal cancer. METHODS: The
      entire mitochondrial genome was screened for somatic mutations in 20 pairs (18
      esophageal squamous cell carcinomas, one adenosquamous carcinoma and one
      adenocarcinoma) of tumor/surrounding normal tissue of esophageal cancers, using
      temporal temperature gradient gel electrophoresis (TTGE), followed by direct DNA
      sequencing to identify the mutations. RESULTS: Fourteen somatic mtDNA mutations
      were identified in 55% (11/20) of tumors analyzed, including 2 novel missense
      mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes
      respectively. Nine mutations (64%) were in the D-loop region. Numerous germline
      variations were found, at least 10 of them were novel and five were missense
      mutations, some of them occurred in evolutionarily conserved domains. Using real
      time quantitative PCR analysis, the mtDNA content was found to increase in some
      tumors and decrease in others. Analysis of molecular and other
      clinicopathological findings does not reveal significant correlation between
      somatic mtDNA mutations and mtDNA content, or between mtDNA content and
      metastatic status. CONCLUSION: Our results demonstrate that somatic mtDNA
      mutations in esophageal cancers are frequent. Some missense and frameshift
      mutations may play an important role in the tumorigenesis of esophageal
      carcinoma. More extensive biochemical and molecular studies will be necessary to
      determine the pathological significance of these somatic mutations.

PMID- 16620378
TI  - High-risk human papilloma virus (HPV) and survival in patients with esophageal
      carcinoma: a pilot study.
AB  - BACKGROUND: Human papilloma virus (HPV) in patients with esophageal carcinoma has
      previously been studied with an average detection rate of 15%, but the role of
      HPV in relation to survival is less clear. In cervical cancer, lung cancer and
      tonsil cancer HPV viral load is a predictive factor for survival and outcome of
      treatment. The primary aim was to study the spectrum of high-risk HPV types in
      esophageal tumors. Secondary, as a pilot study we investigated the association
      between HPV status and the survival rates. METHODS: We compared both the presence
      and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67
      in relation to clinical data from patients with esophageal carcinoma. Survival
      data and tumor samples were retrieved from 100 patients receiving treatment at
      the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples
      were investigated for HPV viral load using real-time PCR. RESULTS: HPV 16 was
      detected in 16% of the patients; no other HPV type was detected. HPV 16 infection
      had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve
      survival after treatment (radiotherapy or chemotherapy). CONCLUSION: Only HPV 16
      was detected among the patients. HPV 16 in esophageal carcinoma patients did not
      influence survival or improve therapy response. However, given the size of the
      study there is a need to examine a larger cohort in order to understand in more
      detail the effect of high risk HPV types in esophageal carcinoma.

PMID- 16620379
TI  - Phylogenomic analysis of vertebrate thrombospondins reveals fish-specific
      paralogues, ancestral gene relationships and a tetrapod innovation.
AB  - BACKGROUND: Thrombospondins (TSPs) are evolutionarily-conserved, extracellular,
      calcium-binding glycoproteins with important roles in cell-extracellular matrix
      interactions, angiogenesis, synaptogenesis and connective tissue organisation.
      Five TSPs, designated TSP-1 through TSP-5, are encoded in the human genome. All
      but one have known roles in acquired or inherited human diseases. To further
      understand the roles of TSPs in human physiology and pathology, it would be
      advantageous to extend the repertoire of relevant vertebrate models. In general
      the zebrafish is proving an excellent model organism for vertebrate biology,
      therefore we set out to evaluate the status of TSPs in zebrafish and two species
      of pufferfish. RESULTS: We identified by bioinformatics that three fish species
      encode larger numbers of TSPs than vertebrates, yet all these sequences group as
      homologues of TSP-1 to -4. By phylogenomic analysis of neighboring genes, we
      uncovered that, in fish, a TSP-4-like sequence is encoded from the gene
      corresponding to the tetrapod TSP-5 gene. Thus, all TSP genes show conservation
      of synteny between fish and tetrapods. In the human genome, the TSP-1, TSP-3, TSP
      4 and TSP-5 genes lie within paralogous regions that provide insight into the
      ancestral genomic context of vertebrate TSPs. CONCLUSION: A new model for TSP
      evolution in vertebrates is presented. The TSP-5 protein sequence has evolved
      rapidly from a TSP-4-like sequence as an innovation in the tetrapod lineage. TSP
      biology in fish is complicated by the presence of additional lineage- and species
      specific TSP paralogues. These novel results give deeper insight into the
      evolution of TSPs in vertebrates and open new directions for understanding the
      physiological and pathological roles of TSP-4 and TSP-5 in humans.

PMID- 16620380
TI  - Theoretical modeling for radiofrequency ablation: state-of-the-art and challenges
      for the future.
AB  - Radiofrequency ablation is an interventional technique that in recent years has
      come to be employed in very different medical fields, such as the elimination of
      cardiac arrhythmias or the destruction of tumors in different locations. In order
      to investigate and develop new techniques, and also to improve those currently
      employed, theoretical models and computer simulations are a powerful tool since
      they provide vital information on the electrical and thermal behavior of ablation
      rapidly and at low cost. In the future they could even help to plan individual
      treatment for each patient. This review analyzes the state-of-the-art in
      theoretical modeling as applied to the study of radiofrequency ablation
      techniques. Firstly, it describes the most important issues involved in this
      methodology, including the experimental validation. Secondly, it points out the
      present limitations, especially those related to the lack of an accurate
      characterization of the biological tissues. After analyzing the current and
      future benefits of this technique it finally suggests future lines and trends in
      the research of this area.

PMID- 16620381
TI  - Spatial and temporal expression of surfactant proteins in hyperoxia-induced
      neonatal rat lung injury.
AB  - BACKGROUND: Bronchopulmonary dysplasia, a complex chronic lung disease in
      premature children in which oxidative stress and surfactant deficiency play a
      crucial role, is characterized by arrested alveolar and vascular development of
      the immature lung. The spatial and temporal patterns of expression of surfactant
      proteins are not yet fully established in newborn infants and animal models
      suffering from BPD. METHODS: We studied the mRNA expression of surfactant
      proteins (SP) A, -B, -C and -D and Clara cell secretory protein (CC10) with RT
      PCR and in situ hybridization and protein expression of CC10, SP-A and -D with
      immunohistochemistry in the lungs of a preterm rat model, in which experimental
      BPD was induced by prolonged oxidative stress. RESULTS: Gene expression of all
      surfactant proteins (SP-A, -B, -C and -D) was high at birth and initially
      declined during neonatal development, but SP-A, -B, and -D mRNA levels increased
      during exposure to hyperoxia compared to room-air controls. Peak levels were
      observed in adult lungs for SP-A, SP-C and CC10. Except for SP-A, the cellular
      distribution of SP-B, -C, -D and CC10, studied with in situ hybridization and/or
      immunohistochemistry, did not change in room air nor in hyperoxia. Exposure to
      normoxia was associated with high levels of SP-A mRNA and protein in alveolar
      type 2 cells and low levels in bronchial Clara cells, whereas hyperoxia induced
      high levels of SP-A expression in bronchial Clara cells. CONCLUSION: The
      increased expression of SP-A mRNA under hyperoxia can be attributed, at least in
      part, to an induction of mRNA and protein expression in bronchial Clara cells.
      The expanded role of Clara cells in the defence against hyperoxic injury suggests
      that they support alveolar type 2 cell function and may play an important role in
      the supply of surfactant proteins to the lower airways.

PMID- 16620382
TI  - PedGenie: an analysis approach for genetic association testing in extended
      pedigrees and genealogies of arbitrary size.
AB  - BACKGROUND: We present a general approach to perform association analyses in
      pedigrees of arbitrary size and structure, which also allows for a mixture of
      pedigree members and independent individuals to be analyzed together, to test
      genetic markers and qualitative or quantitative traits. Our software, PedGenie,
      uses Monte Carlo significance testing to provide a valid test for related
      individuals that can be applied to any test statistic, including transmission
      disequilibrium statistics. Single locus at a time, composite genotype tests, and
      haplotype analyses may all be performed. We illustrate the validity and
      functionality of PedGenie using simulated and real data sets. For the real data
      set, we evaluated the role of two tagging-single nucleotide polymorphisms (tSNPs)
      in the DNA repair gene, NBS1, and their association with female breast cancer in
      462 cases and 572 controls selected to be BRCA1/2 mutation negative from 139 high
      risk Utah breast cancer families. RESULTS: The results from PedGenie were shown
      to be valid both for accurate p-value calculations and consideration of pedigree
      structure in the simulated data set. A nominally significant association with
      breast cancer was observed with the NBS1 tSNP rs709816 for carriage of the rare
      allele (OR = 1.61, 95% CI = 1.10-2.35, p = 0.019). CONCLUSION: PedGenie is a
      flexible and valid statistical tool that is intuitively simple to understand,
      makes efficient use of all the data available from pedigrees without requiring
      trimming, and is flexible to the types of tests to which it can be applied.
      Further, our analyses of real data indicate NBS1 may play a role in the genetic
      etiology of heritable breast cancer.

PMID- 16620383
TI  - Adjusting for dependent comorbidity in the calculation of healthy life
      expectancy.
AB  - BACKGROUND: Healthy life expectancy--sometimes called health-adjusted life
      expectancy (HALE)--is a form of health expectancy indicator that extends measures
      of life expectancy to account for the distribution of health states in the
      population. The World Health Organization has estimated healthy life expectancy
      for 192 WHO Member States using information from health interview surveys and
      from the Global Burden of Disease Study. The latter estimates loss of health by
      cause, age and sex for populations. Summation of prevalent years lived with
      disability (PYLD) across all causes would result in overestimation of the
      severity of the population average health state because of comorbidity between
      conditions. Earlier HALE calculations made adjustments for independent
      comorbidity in adding PYLD across causes. This paper presents a method for
      adjusting for dependent comorbidity using available empirical data. METHODS: Data
      from five large national health surveys were analysed by age and sex to estimate
      "dependent comorbidity" factors for pairs of conditions. These factors were
      defined as the ratio of the prevalence of people with both conditions to the
      product of the two total prevalences for each of the conditions. The resulting
      dependent comorbidity factors were used for all Member States to adjust for
      dependent comorbidity in summation of PYLD across all causes and in the
      calculation of HALE. A sensitivity analysis was also carried out for order
      effects in the proposed calculation method. RESULTS: There was surprising
      consistency in the dependent comorbidity factors across the five surveys. The
      improved estimation of dependent comorbidity resulted in reductions in total PYLD
      per capita ranging from a few per cent in younger adult ages to around 8% in the
      oldest age group (80 years and over) in developed countries and up to 15% in the
      oldest age group in the least developed countries. The effect of the dependent
      comorbidity adjustment on estimated healthy life expectancies is small for some
      regions (high income countries, Eastern Europe, Western Pacific) and ranges from
      an increase of 0.5 to 1.5 years for countries in Latin America, South East Asia
      and Sub-Saharan Africa. CONCLUSION: The available evidence suggests that
      dependent comorbidity is important, and that adjustment for it makes a
      significant difference to resulting HALE estimates for some regions of the world.
      Given the data limitations, we recommend a normative adjustment based on the
      available evidence, and applied consistently across all countries.

PMID- 16620384
TI  - Scientific issues related to the cytology proficiency testing regulations.
AB  - The member organizations of the Cytology Education and Technology Consortium
      believe there are significant flaws in current cytology proficiency testing
      regulations. The most immediate needed modifications include lengthening the
      required testing interval, utilizing stringently validated and continuously
      monitored slides, changing the grading scheme, and changing the focus of the test
      from the individual to laboratory level testing. Integration of new computer
      assisted and located-guided screening technologies into the testing protocols is
      necessary for the testing protocol to be compliant with the law.

PMID- 16620385
TI  - Measuring additive interaction using odds ratios.
AB  - Interaction measured on the additive scale has been argued to be better
      correlated with biologic interaction than when measured on the multiplicative
      scale. Measures of interaction on the additive scale have been developed using
      risk ratios. However, in studies that use odds ratios as the sole measure of
      effect, the calculation of these measures of additive interaction is usually
      performed by directly substituting odds ratios for risk ratios. Yet assessing
      additive interaction based on replacing risk ratios by odds ratios in formulas
      that were derived using the former may be erroneous. In this paper, we evaluate
      the extent to which three measures of additive interaction - the interaction
      contrast ratio (ICR), the attributable proportion due to interaction (AP), and
      the synergy index (S), estimated using odds ratios versus using risk ratios
      differ as the incidence of the outcome of interest increases in the source
      population and/or as the magnitude of interaction increases. Our analysis shows
      that the difference between the two depends on the measure of interaction used,
      the type of interaction present, and the baseline incidence of the outcome.
      Substituting odds ratios for risk ratios, when calculating measures of additive
      interaction, may result in misleading conclusions. Of the three measures, AP
      appears to be the most robust to this direct substitution. Formulas that use
      stratum specific odds and odds ratios to accurately calculate measures of
      additive interaction are presented.

PMID- 16620387
TI  - Deconstructing anti-harm-reduction metaphors; mortality risk from falls and other
      traumatic injuries compared to smokeless tobacco use.
AB  - Anti-harm-reduction advocates sometimes resort to pseudo-analogies to ridicule
      harm reduction. Those opposed to the use of smokeless tobacco as an alternative
      to smoking sometimes suggest that the substitution would be like jumping from a 3
      story building rather than 10 story, or like shooting yourself in the foot rather
      than the head. These metaphors are grossly inappropriate for several reasons,
      notably including the fact that they are misleading about the actual risk levels.
      Based on the available literature on mortality from falls, we estimate that
      smoking presents a mortality risk similar to a fall of about 4 stories, while
      mortality risk from smokeless tobacco is no worse than that from an almost
      certainly non-fatal fall from less than 2 stories. Other metaphors are similarly
      misleading. These metaphors, like other false and misleading anti-harm-reduction
      statements are inherently unethical attempts to prevent people from learning
      accurate health information. Moreover, they implicitly provide bad advice about
      health behavior priorities and are intended to persuade people to stick with a
      behavior that is more dangerous than an available alternative. Finally, the
      metaphors exhibit a flippant tone that seems inappropriate for a serious
      discussion of health science.

PMID- 16620386
TI  - CTL epitope distribution patterns in the Gag and Nef proteins of HIV-1 from
      subtype A infected subjects in Kenya: use of multiple peptide sets increases the
      detectable breadth of the CTL response.
AB  - BACKGROUND: Subtype A is a major strain in the HIV-1 pandemic in eastern Europe,
      central Asia and in certain regions of east Africa, notably in rural Kenya. While
      considerable effort has been focused upon mapping and defining immunodominant CTL
      epitopes in HIV-1 subtype B and subtype C infections, few epitope mapping studies
      have focused upon subtype A. RESULTS: We have used the IFN-gamma ELIspot assay
      and overlapping peptide pools to show that the pattern of CTL recognition of the
      Gag and Nef proteins in subtype A infection is similar to that seen in subtypes B
      and C. The p17 and p24 proteins of Gag and the central conserved region of Nef
      were targeted by CTL from HIV-1-infected Kenyans. Several epitope/HLA
      associations commonly seen in subtype B and C infection were also observed in
      subtype A infections. Notably, an immunodominant HLA-C restricted epitope (Gag
      296-304; YL9) was observed, with 8/9 HLA-CW0304 subjects responding to this
      epitope. Screening the cohort with peptide sets representing subtypes A, C and D
      (the three most prevalent HIV-1 subtypes in east Africa), revealed that peptide
      sets based upon an homologous subtype (either isolate or consensus) only
      marginally improved the capacity to detect CTL responses. While the different
      peptide sets detected a similar number of responses (particularly in the Gag
      protein), each set was capable of detecting unique responses not identified with
      the other peptide sets. CONCLUSION: Hence, screening with multiple peptide sets
      representing different sequences, and by extension different epitope variants,
      can increase the detectable breadth of the HIV-1-specific CTL response.
      Interpreting the true extent of cross-reactivity may be hampered by the use of 15
      mer peptides at a single concentration and a lack of knowledge of the sequence
      that primed any given CTL response. Therefore, reagent choice and knowledge of
      the exact sequences that prime CTL responses will be important factors in
      experimentally defining cross-reactive CTL responses and their role in HIV-1
      disease pathogenesis and validating vaccines aimed at generating broadly cross
      reactive CTL responses.

PMID- 16620388
TI  - Prevalence study of Legionella spp. contamination in ferries and cruise ships.
AB  - BACKGROUND: In the last years, international traffic volume has significantly
      increased, raising the risk for acquisition of infectious diseases. Among travel
      associated infections, increased incidence of legionellosis has been reported
      among travellers. Aim of our study was: to describe the frequency and severity of
      Legionella spp. contamination in ferries and cruise ships; to compare the levels
      of contamination with those indicated by the Italian ministerial guidelines for
      control and prevention of legionellosis, in order to assess health risks and to
      adopt control measures. METHOD: A prevalence study was carried out on 9 ships
      docked at the seaports of northern Sardinia in 2004. Water samples were collected
      from critical sites: passenger cabins, crew cabins, kitchens, coffee bars, rooms
      of the central air conditioning system. It was performed a qualitative and
      quantitative identification of Legionella spp. and a chemical, physical and
      bacteriological analysis of water samples. RESULTS: Forty-two percent (38/90)
      water samples were contaminated by Legionella spp.. Positive samples were mainly
      drawn from showers (24/44), washbasins (10/22). L. pneumophila was isolated in
      42/44 samples (95.5%), followed by L. micdadei (4.5%). Strains were identified as
      L. pneumophila serogroup 6 (45.2%; 19 samples), 2-14 (42.9%), 5 (7.1%) and 3
      (4.8%). Legionella spp. load was high; 77.8% of the water samples contained >
      10(4) CFU/L. Low residual free chlorine concentration (0-0.2 mg/L) was associated
      to a contamination of the 50% of the water samples. CONCLUSION: Legionella is an
      ubiquitous bacterium that could create problems for public health. We identified
      Legionella spp. in 6/7 ferries. Microbial load was predominantly high (> 10(4)
      CFU/L or ranging from 10(3) to 10(4) CFU/L). It is matter of concern when
      passengers are subjects at risk because of Legionella spp. is an opportunist that
      can survive in freshwater systems; high bacterial load might be an important
      variable related to disease's occurrence. High level of contamination required
      disinfecting measures, but does not lead to a definitive solution to the problem.
      Therefore, it is important to identify a person responsible for health safety in
      order to control the risk from exposure and to apply preventive measures,
      according to European and Italian guidelines.

PMID- 16620389
TI  - Permeabilization of the mycobacterial envelope for protein cytolocalization
      studies by immunofluorescence microscopy.
AB  - BACKGROUND: The establishment of the cellular localization of proteins in M.
      tuberculosis will provide of valuable information for the identification of new
      drug/vaccine/diagnostic targets. Cytolocalization by inmunofluorescence
      microscopy has been limited in mycobacteria because to difficulties in
      effectively permeabilize it. RESULTS: A treatment combining lysozyme with triton
      X-100 was found to be an effective permeabilization method of the mycobacterial
      envelope. CONCLUSION: A rapid and simple permeabilization protocol has been
      successfully assessed in pure cultures of both Mycobacterium smegmatis and
      Mycobacterium tuberculosis H37Rv. This method can be successful used in the
      cytolocalization of proteins by immunolabeling.

PMID- 16620390
TI  - Health profiles of 996 melanoma survivors: the M. D. Anderson experience.
AB  - BACKGROUND: The incidence and survival of melanoma are increasing, but little is
      known about its long-term health effects in adult survivors. METHODS: A health
      survey was available from 996 melanoma survivors (577 treated with surgery alone,
      and 391 with combined treatments). Their medical/physiologic and psychosocial
      responses were analyzed and compared with those of the survivors from other
      cancers. RESULTS: The melanoma survivors were 44.8 +/- 12.8 years of age at
      diagnosis (significantly younger than the survivors of other cancers) and 63.7 +/
      12.8 years at survey. Melanoma survivors were less likely to report that cancer
      had affected their health than survivors of other cancers (15.8% vs. 34.9%). The
      577 individuals treated with surgery alone reported arthritis/osteoporosis,
      cataracts, and heart problems most frequently (less often than survivors of other
      cancers). The 391 individuals who had undergone combined treatments reported
      circulation problems and kidney problems generally as often as survivors of other
      cancers. Health problems were not associated with number of decades since
      diagnosis but with age at diagnosis, treatment modality, and family
      relationships. CONCLUSION: We present information from a large cohort of long
      term survivors of melanoma. As a group, they were less likely to report that
      cancer had affected their overall health than survivors of other cancers; a
      number of disease related and psychosocial factors appear to influence their
      health profiles.

PMID- 16620391
TI  - Breast tumor copy number aberration phenotypes and genomic instability.
AB  - BACKGROUND: Genomic DNA copy number aberrations are frequent in solid tumors,
      although the underlying causes of chromosomal instability in tumors remain
      obscure. Genes likely to have genomic instability phenotypes when mutated (e.g.
      those involved in mitosis, replication, repair, and telomeres) are rarely mutated
      in chromosomally unstable sporadic tumors, even though such mutations are
      associated with some heritable cancer prone syndromes. METHODS: We applied array
      comparative genomic hybridization (CGH) to the analysis of breast tumors. The
      variation in the levels of genomic instability amongst tumors prompted us to
      investigate whether alterations in processes/genes involved in maintenance and/or
      manipulation of the genome were associated with particular types of genomic
      instability. RESULTS: We discriminated three breast tumor subtypes based on
      genomic DNA copy number alterations. The subtypes varied with respect to level of
      genomic instability. We find that shorter telomeres and altered telomere related
      gene expression are associated with amplification, implicating telomere attrition
      as a promoter of this type of aberration in breast cancer. On the other hand, the
      numbers of chromosomal alterations, particularly low level changes, are
      associated with altered expression of genes in other functional classes (mitosis,
      cell cycle, DNA replication and repair). Further, although loss of function
      instability phenotypes have been demonstrated for many of the genes in model
      systems, we observed enhanced expression of most genes in tumors, indicating that
      over expression, rather than deficiency underlies instability. CONCLUSION: Many
      of the genes associated with higher frequency of copy number aberrations are
      direct targets of E2F, supporting the hypothesis that deregulation of the Rb
      pathway is a major contributor to chromosomal instability in breast tumors. These
      observations are consistent with failure to find mutations in sporadic tumors in
      genes that have roles in maintenance or manipulation of the genome.

PMID- 16620392
TI  - Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats.
AB  - BACKGROUND: Prenatal cocaine exposure produces attentional deficits which to
      persist through early childhood. Given the role of norepinephrine (NE) in
      attentional processes, we examined the forebrain NE systems from prenatal cocaine
      exposed rats. Cocaine was administered during pregnancy via the clinically
      relevant intravenous route of administration. Specifically, we measured alpha2
      adrenergic receptor (alpha2-AR) density in adolescent (35-days-old) rats, using
      [3H]RX821002 (5 nM). RESULTS: Sex-specific alterations of alpha2-AR were found in
      the hippocampus and amygdala of the cocaine-exposed animals, as well as an
      upregulation of alpha2-AR in parietal cortex. CONCLUSION: These data suggest that
      prenatal cocaine exposure results in a persistent alteration in forebrain NE
      systems as indicated by alterations in receptor density. These neurochemical
      changes may underlie behavioral abnormalities observed in offspring attentional
      processes following prenatal exposure to cocaine.

PMID- 16620393
TI  - Intraprostatic injection of botulinum toxin type-A relieves bladder outlet
      obstruction in human and induces prostate apoptosis in dogs.
AB  - BACKGROUND: With the increasing interest with botulinum toxin--A (BTX-A)
      application in the lower urinary tract, we investigated the BTX-A effects on the
      canine prostate and also in men with bladder outlet obstruction (BOO) due to
      benign prostatic hyperplasia (BPH). METHODS: Transperineal injection into the
      prostate using transrectal ultrasound (TRUS) was performed throughout the study.
      Saline with or without 100 U of BTX-A was injected into mongrel dogs prostate.
      One or 3 months later, the prostate was harvested for morphologic and apoptotic
      study. In addition, eight BPH patients refractory to alpha-blockers were treated
      with ultrasound guided intraprostatic injection of 200 U of BTX-A. RESULTS: In
      the BTX-A treated dogs, atrophy and diffuse apoptosis was observed with H&E stain
      and TUNEL stain at 1 and 3 months. Clinically, the mean prostate volume, symptom
      score, and quality of life index were significantly reduced by 18.8%, 73.1%, and
      61.5% respectively. Maximal flow rate significantly increased by 72.0%.
      CONCLUSION: Intraprostatic BTX-A injection induces prostate apotosis in dogs and
      relieves BOO in humans. It is therefore a promising alternative treatment for
      refractory BOO due to BPH.

PMID- 16620394
TI  - Display of a thermostable lipase on the surface of a solvent-resistant bacterium,
      Pseudomonas putida GM730, and its applications in whole-cell biocatalysis.
AB  - BACKGROUND: Whole-cell biocatalysis in organic solvents has been widely applied
      to industrial bioprocesses. In two-phase water-solvent processes, substrate
      conversion yields and volumetric productivities can be limited by the toxicity of
      solvents to host cells and by the low mass transfer rates of the substrates from
      the solvent phase to the whole-cell biocatalysts in water. RESULTS: To solve the
      problem of solvent toxicity, we immobilized a thermostable lipase (TliA) from
      Pseudomonas fluorescens on the cell surface of a solvent-resistant bacterium,
      Pseudomonas putida GM730. Surface immobilization of enzymes eliminates the mass
      transfer limitation imposed by the cell wall and membranes. TliA was successfully
      immobilized on the surface of P. putida cells using the ice-nucleation protein
      (INP) anchoring motif from Pseudomonas syrinage. The surface location was
      confirmed by flow cytometry, protease accessibility and whole-cell enzyme
      activity using a membrane-impermeable substrate. Three hundred and fifty units of
      whole-cell hydrolytic activity per gram dry cell mass were obtained when the
      enzyme was immobilized with a shorter INP anchoring motif (INPNC). The surface
      immobilized TliA retained full enzyme activity in a two-phase water-isooctane
      reaction system after incubation at 37 degrees C for 12 h, while the activity of
      the free form enzyme decreased to 65% of its initial value. Whole cells
      presenting immobilized TliA were shown to catalyze three representative lipase
      reactions: hydrolysis of olive oil, synthesis of triacylglycerol and chiral
      resolution. CONCLUSION: In vivo surface immobilization of enzymes on solvent
      resistant bacteria was demonstrated, and appears to be useful for a variety of
      whole-cell bioconversions in the presence of organic solvents.

PMID- 16620395
TI  - Toll-like receptor-4 mediates cigarette smoke-induced cytokine production by
      human macrophages.
AB  - BACKGROUND: The major risk factor for the development of COPD is cigarette
      smoking. Smoking causes activation of resident cells and the recruitment of
      inflammatory cells into the lungs, which leads to release of pro-inflammatory
      cytokines, chemotactic factors, oxygen radicals and proteases. In the present
      study evidence is found for a new cellular mechanism that refers to a link
      between smoking and inflammation in lungs. METHODS: Employing human monocyte
      derived macrophages, different techniques including FACS analysis, Cytometric
      Bead Array Assay and ELISA were achieved to evaluate the effects of CS on pro
      inflammatory cytokine secretion including IL-8. Then, Toll-like receptor
      neutralization was performed to study the involvement of Toll-like receptor-4 in
      IL-8 production. Finally, signaling pathways in macrophages after exposure to CS
      medium were investigated performing ELISA and Western analysis. RESULTS: We
      demonstrate that especially human monocytes are sensitive to produce IL-8 upon
      cigarette smoke stimulation compared to lymphocytes or neutrophils. Moreover,
      monocyte-derived macrophages produce high amounts of the cytokine. The IL-8
      production is dependent on Toll-like receptor 4 stimulation and LPS is not
      involved. Further research resolved the cellular mechanism by which cigarette
      smoke induces cytokine production in monocyte-derived macrophages. Cigarette
      smoke causes subsequently a concentration-dependent phosphorylation of IRAK and
      degradation of TRAF6. Moreover, IkappaBalpha was phosphorylated which suggests
      involvement of NF-kappaB. In addition, NFkappaB-inhibitor blocked cigarette smoke
      induced IL-8 production. CONCLUSION: These findings link cigarette smoke to
      inflammation and lead to new insights/therapeutic strategies in the pathogenesis
      of lung emphysema.

PMID- 16620396
TI  - T null and M null genotypes of the glutathione S-transferase gene are risk factor
      for CAD independent of smoking.
AB  - BACKGROUND: The association of the deletion in GSTT1 and GSTM1 genes with
      coronary artery disease (CAD) among smokers is controversial. In addition, no
      such investigation has previously been conducted among Arabs. METHODS: We
      genotyped 1054 CAD patients and 762 controls for GSTT1 and GSTM1 deletion by
      multiplex polymerase chain reaction. Both CAD and controls were Saudi Arabs.
      RESULTS: In the control group (n = 762), 82.3% had the T wild M wildgenotype, 9%
      had the Twild M null, 2.4% had the Tnull M wild and 6.3% had the Tnull M null
      genotype. Among the CAD group (n = 1054), 29.5% had the Twild M wild genotype,
      26.6% (p < .001) had the Twild M null, 8.3% (p < .001) had the Tnull M wild and
      35.6% (p < .001) had the Tnull M null genotype, indicating a significant
      association of the Twild M null, Tnull M wild and Tnull M null genotypes with
      CAD. Univariate analysis also showed that smoking, age, hypercholesterolemia and
      hypertriglyceridemia, diabetes mellitus, family history of CAD, hypertension and
      obesity are all associated with CAD, whereas gender and myocardial infarction are
      not. Binary logistic regression for smoking and genotypes indicated that only M
      null and Tnullare interacting with smoking. However, further subgroup analysis
      stratifying the data by smoking status suggested that genotype-smoking
      interactions have no effect on the development of CAD. CONCLUSION: GSTT1 and
      GSTM1 null-genotypes are risk factor for CAD independent of genotype-smoking
      interaction.

PMID- 16620397
TI  - Fold-recognition and comparative modeling of human alpha2,3-sialyltransferases
      reveal their sequence and structural similarities to CstII from Campylobacter
      jejuni.
AB  - BACKGROUND: The 3-D structure of none of the eukaryotic sialyltransferases
      (SiaTs) has been determined so far. Sequence alignment algorithms such as BLAST
      and PSI-BLAST could not detect a homolog of these enzymes from the protein
      databank. SiaTs, thus, belong to the hard/medium target category in the CASP
      experiments. The objective of the current work is to model the 3-D structures of
      human SiaTs which transfer the sialic acid in alpha2,3-linkage viz., ST3Gal I,
      II, III, IV, V, and VI, using fold-recognition and comparative modeling methods.
      The pair-wise sequence similarity among these six enzymes ranges from 41 to 63%.
      RESULTS: Unlike the sequence similarity servers, fold-recognition servers
      identified CstII, a alpha2,3/8 dual-activity SiaT from Campylobacter jejuni as
      the homolog of all the six ST3Gals; the level of sequence similarity between
      CstII and ST3Gals is only 15-20% and the similarity is restricted to well
      characterized motif regions of ST3Gals. Deriving template-target sequence
      alignments for the entire ST3Gal sequence was not straightforward: the fold
      recognition servers could not find a template for the region preceding the L
      motif and that between the L- and S-motifs. Multiple structural templates were
      identified to model these regions and template identification-modeling-evaluation
      had to be performed iteratively to choose the most appropriate templates. The
      modeled structures have acceptable stereochemical properties and are also able to
      provide qualitative rationalizations for some of the site-directed mutagenesis
      results reported in literature. Apart from the predicted models, an unexpected
      but valuable finding from this study is the sequential and structural relatedness
      of family GT42 and family GT29 SiaTs. CONCLUSION: The modeled 3-D structures can
      be used for docking and other modeling studies and for the rational
      identification of residues to be mutated to impart desired properties such as
      altered stability, substrate specificity, etc. Several studies in literature have
      focused on the development of tools and/or servers for the large-scale/automated
      modeling of 3-D structures of proteins. In contrast, the present study focuses on
      modeling the 3-D structure of a specific protein of interest to a biochemist and
      illustrates the associated difficulties. It is also able to establish a
      sequence/structure relationship between sialyltransferases of two distinct
      families.

PMID- 16620398
TI  - Survival of TNF antagonists in spondylarthritis is better than in rheumatoid
      arthritis. Data from the Spanish registry BIOBADASER.
AB  - The aim of the present work is to compare drug survival and safety of infliximab,
      etanercept, and adalimumab (tumor necrosis factor [TNF] antagonists) in
      spondylarthritis (SpA) with those of rheumatoid arthritis (RA). To this purpose,
      we analysed the data in BIOBADASER (2000-2005), a drug registry launched in 2000
      for long-term follow-up of the safety of these biologics in rheumatic diseases.
      The rates of drug discontinuation and adverse events (AEs) in SpA (n = 1,524)
      were estimated and compared with those of RA (n = 4,006). Cox regression analyses
      were used to adjust for independent factors. Total exposure to TNF antagonists
      for SpA was 2,430 patient-years and 7,865 for RA. Drug survival in SpA was
      significantly greater than in RA at 1, 2, and 3 years. The hazard ratio (HR) for
      discontinuation in SpA compared with RA was 0.66 (95% confidence interval [CI],
      0.57-0.76) after adjustment for age, gender, and use of infliximab. The
      difference remained after controlling for the individual medication and its place
      in the sequence of treatment. There were fewer SpA patients with AEs (17%) than
      RA patients (26%; p < 0.001). The HR for AEs in SpA was 0.80 (95% CI, 0.70-0.91)
      compared with RA after adjustment for age, disease duration, and use of
      infliximab. In conclusion, due in part to a better safety profile, survival of
      TNF antagonists in SpA is better than in RA. TNF antagonists are at present a
      safe and effective therapeutic option for long-term treatment of patients with
      SpA failing to respond to traditional drugs. Because chronic therapy is
      necessary, continual review of this issue is necessary.

PMID- 16620399
TI  - Sickle cell disease.

PMID- 16620400
TI  - Angina (unstable).

PMID- 16620401
TI  - Atrial fibrillation (recent onset).

PMID- 16620402
TI  - Primary prevention: dyslipidaemia.

PMID- 16620403
TI  - Primary prevention: hypertension.

PMID- 16620404
TI  - Stroke prevention.

PMID- 16620405
TI  - Thromboembolism.

PMID- 16620406
TI  - Asthma and other wheezing disorders in children.

PMID- 16620407
TI  - Autism.

PMID- 16620408
TI  - Bronchiolitis.

PMID- 16620409
TI  - Cardiorespiratory arrest in children.

PMID- 16620410
TI  - Croup.

PMID- 16620411
TI  - Gastro-oesophageal reflux in children.

PMID- 16620412
TI  - Nosebleeds in children.

PMID- 16620413
TI  - Urinary tract infection in children.

PMID- 16620414
TI  - Diabetic nephropathy.

PMID- 16620415
TI  - Foot ulcers and amputations in diabetes.

PMID- 16620416
TI  - Glycaemic control in type 2 diabetes.

PMID- 16620417
TI  - Hypertension in diabetes.

PMID- 16620418
TI  - Appendicitis.

PMID- 16620419
TI  - Acute cholecystitis.

PMID- 16620420
TI  - Colonic diverticular disease.

PMID- 16620421
TI  - Colorectal cancer.

PMID- 16620422
TI  - Constipation in adults.

PMID- 16620423
TI  - Gastro-oesophageal reflux disease.

PMID- 16620424
TI  - Stomach cancer.

PMID- 16620425
TI  - Ear wax.

PMID- 16620426
TI  - Meniere's disease.

PMID- 16620427
TI  - Middle ear pain and trauma during air travel.

PMID- 16620428
TI  - Otitis externa.

PMID- 16620429
TI  - Seasonal allergic rhinitis.

PMID- 16620430
TI  - Tinnitus.

PMID- 16620431
TI  - Tonsillitis.

PMID- 16620432
TI  - Primary hypothyroidism.

PMID- 16620433
TI  - Acute anterior uveitis.

PMID- 16620434
TI  - Bacterial conjunctivitis.

PMID- 16620435
TI  - Cataract.

PMID- 16620436
TI  - Ocular herpes simplex.

PMID- 16620437
TI  - Trachoma.

PMID- 16620439
TI  - HIV: mother to child transmission.

PMID- 16620438
TI  - HIV infection.

PMID- 16620440
TI  - Tuberculosis in people with HIV.

PMID- 16620441
TI  - Amoebic dysentery.

PMID- 16620442
TI  - Chickenpox.

PMID- 16620443
TI  - Chronic hepatitis C.

PMID- 16620444
TI  - Malaria: prevention in travellers.

PMID- 16620445
TI  - Postherpetic neuralgia.

PMID- 16620446
TI  - Tuberculosis.

PMID- 16620447
TI  - Kidney stones.

PMID- 16620448
TI  - Benign prostatic hyperplasia.

PMID- 16620449
TI  - Testicular cancer: seminoma.

PMID- 16620450
TI  - Anorexia nervosa.

PMID- 16620451
TI  - Bulimia nervosa.

PMID- 16620452
TI  - Dementia.

PMID- 16620453
TI  - Generalised anxiety disorder.

PMID- 16620454
TI  - Obsessive compulsive disorder.

PMID- 16620455
TI  - Post-traumatic stress disorder.

PMID- 16620456
TI  - Schizophrenia.

PMID- 16620457
TI  - Carpal tunnel syndrome.

PMID- 16620458
TI  - Chronic fatigue syndrome.

PMID- 16620459
TI  - Hip fracture.

PMID- 16620460
TI  - Musculoskeletal disorders. Non-steroidal anti-inflammatory drugs.

PMID- 16620461
TI  - Osteoarthritis of the knee.

PMID- 16620462
TI  - Shoulder pain.

PMID- 16620463
TI  - Altitude sickness.

PMID- 16620464
TI  - Epilepsy.

PMID- 16620465
TI  - Headache (chronic tension-type).

PMID- 16620466
TI  - Multiple sclerosis.

PMID- 16620467
TI  - Trigeminal neuralgia.

PMID- 16620468
TI  - Burning mouth syndrome.

PMID- 16620469
TI  - Halitosis.

PMID- 16620470
TI  - Postoperative pulmonary infections.

PMID- 16620471
TI  - Paracetamol (acetaminophen) poisoning.

PMID- 16620472
TI  - Postnatal depression.

PMID- 16620473
TI  - Pre-eclampsia and hypertension.

PMID- 16620474
TI  - Asthma.

PMID- 16620475
TI  - Lung cancer.

PMID- 16620476
TI  - Genital herpes.

PMID- 16620477
TI  - Partner notification.

PMID- 16620478
TI  - Athlete's foot.

PMID- 16620479
TI  - Fungal nail infections.

PMID- 16620480
TI  - Head lice.

PMID- 16620481
TI  - Herpes labialis.

PMID- 16620482
TI  - Malignant melanoma (non-metastatic).

PMID- 16620483
TI  - Squamous cell carcinoma of the skin (non-metastatic).

PMID- 16620484
TI  - Warts.

PMID- 16620485
TI  - Wrinkles.

PMID- 16620486
TI  - Breast pain.

PMID- 16620487
TI  - Candidiasis (vulvovaginal).

PMID- 16620488
TI  - Domestic violence towards women.

PMID- 16620489
TI  - Fibroids (uterine myomatosis, leiomyomas).

PMID- 16620490
TI  - Menorrhagia.

PMID- 16620491
TI  - Polycystic ovary syndrome.

PMID- 16620492
TI  - Pyelonephritis in non-pregnant women.

PMID- 16620493
TI  - Stress incontinence.

PMID- 16620494
TI  - Burns (minor thermal).

PMID- 16620496
TI  - Chiral separation of norlaudanosoline, laudanosoline, laudanosine,
      chlorthalidone, and three benzoin derivatives using amino acid based molecular
      micelles.
AB  - In this study, 18 polymeric single amino acid and dipeptide surfactants are
      examined, and their performances, in terms of enantioselectivity, are compared
      for norlaudanosoline, laudanosoline, laudanosine, chlorthalidone, benzoin,
      benzoin methyl, and benzoin ethyl enantiomers. Several aspects of amino acid
      based polymeric surfactants including comparison of single amino acid versus
      dipeptide, amino acid order, steric effect, and effect of the position of the
      chiral center of dipeptide surfactants on the chiral selectivity of these
      optically active compounds are discussed.

PMID- 16620495
TI  - Identification of isoflavonoids in several kudzu samples by high-performance
      liquid chromatography coupled with electrospray ionization tandem mass
      spectrometry.
AB  - Pueraria lobata is a rich source of isoflavonoids. The detection and
      identification of isoflavonoid components from Pueraria radix (RP), callus and
      cell cultures, is very important for the safest and most effective use of kudzu
      as a medicinal plant, and for the studies on quantitative analysis and secondary
      metabolism of isoflavonoids in vitro cultures. Liquid chromatography is coupled
      with negative and positive electrospray ionization (ESI) tandem mass spectrometry
      (MS-MS), and photodiode array detection is used to characterize and detect
      isoflavonoids in root, callus, and cell samples of P. lobata. Characteristic
      product ions of aglycones, O-glucosides, and C-glucosides were obtained from the
      full-scan ESI-MS chromatography of the major peaks and the MS-MS spectra of the
      protonated ions. Five major components of puerarin, daidzin-6"-O-acetylester,
      genistin-6"-O-malonylester, biochanin A-7-O-glucoside-6"-O-malonylester, and
      daidzein are detected and identified from the methanolic extract of P. lobata
      callus cultures. The major isoflavonoid components of P. lobata cell suspension
      cultures are identified as puerarin, daidzin, daidzin-6"-O-acetylester, genistin
      6"-O-malonylester, biochanin A-7-O-glucoside-6"-O-malonylester, genistein-8-C
      glucoside-6"-O-malonylester, and daidzein, on the basis of ESI-MS and MS-MS
      spectra analysis. Likewise, puerarin, daidzin, genistein-6"-O-malonylester, 3'
      methoxypuerarin, and daidzein are detected and identified from RP. Of those
      isoflavonoid components detected, daidzin-6"-O-acetylester is a new isoflavonoid
      glucoside and is for the first time detected from P. lobata cultures in vitro.

PMID- 16620497
TI  - Method validation for the simultaneous determination of fecal sterols in surface
      waters by gas chromatography-mass spectrometry.
AB  - Besides microbiological methods, fecal pollution of surface waters is estimated
      by gas chromatographic (GC) determination of sterols present in human and animal
      sewage effluents. The most frequently used biomarkers for the evaluation of
      contamination levels include coprostanol, cholesterol, dihydrocholesterol,
      stigmasterol, beta-sitosterol, and stigmastanol. Although several GC techniques
      are used to measure these compounds in aquatic systems, the analytical
      performance of GC-mass spectrometric (MS) determination of these sterols has not
      been systematically characterized. Therefore, the aim of this work is to validate
      a simple and rapid GC-MS method for the simultaneous analysis of six sterols,
      considering all parameters and requirements defined by Good Laboratory Practice.
      Following liquid-liquid extraction of spiked surface water samples, the extracts
      are silylated and analyzed by GC-MS. The method is evaluated for linearity and
      limits of detection and quantitation, as well as for precision, extraction
      efficiency, and stability. The assay is linear up to 160 ng; the limits of
      detection and quantitation are 5-10 ng and 20 ng, respectively. The within- and
      between-day precision ranged from 1% to 9% and 1% to 16%, respectively. The
      extraction efficiency was 65-80%. The stability studies indicate that the sterols
      in surface water samples begin to degrade after 24 h of refrigerated storage.
      However, three freeze/thaw cycles could be performed without their decomposition.
      The method is applied to the analysis of surface water and wastewater samples.
      The technical advantages make this GC-MS analysis suitable for routine
      environmental monitoring of fecal pollution in aquatic systems.

PMID- 16620498
TI  - Retention behavior of neutral solutes in pressurized flow-driven capillary
      electrochromatography using an ODS column.
AB  - Several alkyl benzenes are separated by pressurized flow-driven capillary
      electrochromatography using a temperature-controlled capillary column packed with
      octadecyl siloxane-modified silica gel, and the effect of applied voltage on the
      retention is investigated. The van't Hoff plot shows good linearity at the column
      temperature between 305 and 330 K under applications from -6 to +6 kV. The
      applied voltage causes a relatively large variation in the enthalpy and the
      entropy of transfer of the solute from the mobile phase to the stationary phase
      (> 20%). However, the direction of variation in the enthalpy is almost opposite
      to that in the entropy, both of which might compensate each other. Therefore, the
      retention factor is not significantly varied (< 4%) by the application of
      voltage.

PMID- 16620499
TI  - Determination of [S,S']-ethylenediaminedisuccinic acid by high-performance liquid
      chromatography.
AB  - A new high-performance liquid chromatography (HPLC) method for the determination
      of ethylenediaminedisuccinic acid (EDDS) is presented. Free EDDS(4-) and EDDS
      complexes with divalent metals undergo conversion to the Fe(III) complex in the
      presence of Fe(III)Cl(3). Fe(III)EDDS is separated by HPLC on an ion exchange
      column using (NH(4))(2)SO(4) eluent with detection at 258 nm. The detection limit
      is 0.01 microM. The method is applied to natural waters and soil solution
      samples. A background of natural water results in a reduction in EDDS peak area.
      The method is suited for EDDS analysis in samples with well-defined, simple
      matrices such as those used in laboratory experiments or biodegradation studies.

PMID- 16620500
TI  - Analysis of trace amount of bank dye and lachrymators from exploding bank devices
      by solid-phase microextraction and gas chromatography-mass spectrometry.
AB  - Solid-phase microextraction (SPME) is a fast, solvent-free alternative to
      conventional sample preparation techniques. This technique involves exposing a
      fused silica fiber that has been coated with a stationary phase to an aqueous
      solution or its headspace to selectively extract compounds from their matrix. The
      fiber is then removed, and the analytes are thermally desorbed in the injector of
      a gas chromatograph. By sampling from the headspace above sample matrices, SPME
      can be used to extract target analytes from very complex matrices. In this study,
      SPME in the headspace is used in developing a method for the dye 1
      methylaminoanthraquinone (MAAQ) and two lachrymators:
      orthochlorobenzalmalononitrile (CS) (tear gas) and 2-chloroacetophenone (CN)
      (tear gas). The focus is to develop a robust method to minimize sample
      preparation and to reduce matrix interferences encountered by other extraction
      techniques. In developing the method, several fibers are studied for their
      affinity for the compounds of interest. Although this method is developed for
      qualitative analysis, the extraction time and temperature profile are thoroughly
      investigated to provide the optimal conditions. The use of a salt solution is
      evaluated to increase the partitioning of MAAQ into the headspace. Using this
      method, qualitative extraction is achieved for the analysis of CN, CS, and MAAQ
      from its matrices. CN and CS are extracted in less than 5 min, though MAAQ needed
      more than 15 min to achieve a reasonable response. If more sensitivity is
      required, the use of a salt solution increases the response of MAAQ by 90-fold.

PMID- 16620501
TI  - Mathematical discretization of size-exclusion chromatograms applied to commercial
      corn maltodextrins.
AB  - Discretization of a size-exclusion chromatography (SEC) chromatogram is shown
      here to be an important calculation for characterizing the distribution of a
      polydisperse polymer, especially when the polydispersity is large. Commercial
      poly-glucose maltodextrins are known to have such a polydispersity. A
      mathematical discretization method with Gaussian peaks centered on each
      individual degree of polymerization is proposed and is performed on the entire
      SEC chromatogram for three different grades of corn maltodextrins. Because SEC
      and high-performance anion exchange chromatography with pulsed amperometric
      detection (HPAEC-PAD) are based on different separation mechanisms, they can be
      considered orthogonal techniques, and HPAEC-PAD was therefore used to validate
      the SEC discretization procedure. Because this validation proved satisfactory for
      all commercially available oligomers, the discretization is extended to all of
      their SEC chromatograms. Comparing the number-average molar weight and the weight
      average molar weight before and after the mathematical discretization verifies
      that such a mathematical treatment does not denaturate the chromatogram. This
      approach tentatively leads to a more exhaustive characterization of a broadly
      polydisperse sample, such as maltodextrins, than was previously available, as it
      (i) gets rid of the apparent, chemically irrelevant, continuous molar weight
      distribution obtained by raw SEC and (ii) addresses the current detection and
      quantitation limits of the HPAEC-PAD technique without any sample treatment.

PMID- 16620502
TI  - One-step isolation and identification of hydroxylamino-dinitrotoluenes, unstable
      products from 2,4,6-trinitrotoluene metabolites, with thin-layer chromatography
      and laser time-of-flight mass spectrometry.
AB  - Two kinds of hydroxylamino-dinitrotoluenes (HADNTs), 2-hydroxylamino-4,6
      dinitrotoluene (2HADNT) and 4-hydroxylamino-2,6-dinitrotoluene (4HADNT), are
      known to be major metabolites produced from 2,4,6-trinitrotoluene (TNT) by
      bacteria. These chemicals could not be identified as TNT metabolites produced by
      Pseudomonas sp. strain TM15 because the mass spectra of these chemicals could not
      be obtained by liquid chromatography-mass spectrometry (MS) or gas chromatography
      MS, which are the classic methods for identifying the metabolites of xenobiotics.
      However, these problems are overcome by isolating 2HADNT and 4HADNT from TNT
      metabolites with one-step thin-layer chromatography using dichloromethane as the
      developing solvent, and individually extracting them into acetonitrile by
      collecting spots of 2HADNT and 4HADNT. The purity of each HADNT was approximately
      98%, based on the results of high-performance liquid chromatographic analyses.
      2HADNT and 4HADNT are identified by obtaining their mass spectra with laser time
      of-flight MS. 2HADNT and 4HADNT dissolve in distilled water and are spontaneously
      broken down with time. Also, heat treatment (increasing temperatures) and
      dissolved oxygen accelerate the destruction of HADNTs. This technique may be
      applicable for the identification and exact quantitative analysis of unstable and
      fragile compounds such as HADNTs.

PMID- 16620503
TI  - Gas chromatographic applications with the dielectric barrier discharge detector.
AB  - With gas chromatography, there are many more choices for detectors when compared
      to other separation disciplines in analytical chemistry. The presence of
      sensitive and selective detectors aids in easing the separation requirements
      imposed on the capillary column. The current gas phase detectors, however, do not
      completely fulfill contemporary analytical needs. One example is in the area of
      ultratrace analysis of permanent gases for semiconductor industry. Another
      example is in the area of environmental/industrial hygiene monitoring for
      compounds such as 1,3-butadiene or vinyl chloride. The dielectric barrier
      discharge detector, a new highly sensitive detector with tuneable selectivity,
      has recently been innovated and commercialized. In this paper, the principle of
      operation of the detector, along with critical challenging industrial
      applications such as the analysis of oxygenated compounds, sulfur-containing
      compounds, and other compounds of industrial significance is presented.

PMID- 16620504
TI  - Negative temperature programming using microwave open tubular gas chromatography.
AB  - A microwave gas chromatography (GC) column oven is engineered to generate a
      uniform microwave field around an open tubular column with the elimination of
      cold spots, which are common in a domestic microwave oven. Short cool-down time
      in microwave heating makes it possible to employ negative temperature programming
      for the enhanced separation of compounds during the process. The feasibility of
      negative temperature programming in microwave GC is investigated for the analysis
      and quantitation of four different pairs of nonvolatile and volatile compounds.
      The influence of intermediate column cooling rate, holding time in the cooling
      ramp, and reheating rate after the cooling ramp for enhanced resolution are
      investigated. The results obtained from negative temperature programming are
      compared with those from positive temperature programming. Negative temperature
      programming affords greater resolution of some critical pairs of analytes.

PMID- 16620505
TI  - Process analytical technology for chromatography.
AB  - A major United States Food and Drug Administration effort is devoted to process
      analytical technology (PAT), which is emerging as the likely "surprise" of the
      second half of the decade. PAT is an approach to monitoring, manufacturing, and
      other processes on a continuous rather than discrete basis. It carries the future
      promise of new methods of production. Building PAT into a chromatography system
      provides a significant cost and quality advantage to high volume multitest
      laboratories and provides a significant marketing advantage to the first
      suppliers able to implement such an approach.

PMID- 16620506
TI  - Assessing the reproducibility of an analytical method.
AB  - The reproducibility of a validated analytical method may require reassessment
      because of various reasons, such as the transfer between laboratories or
      companies, changes in the instruments or software platforms (or both), or changes
      in critical reagents, among others. This paper is a demonstration of an assay
      bridging study in evaluating reproducibility. The approach is simple but very
      informative and offers many advantages over existing approaches.

PMID- 16620507
TI  - Reversed headspace analysis for characterization, identification, and analysis of
      solid and liquid matrices: Part I.
AB  - This paper offers a methodology of an experimentally simple reversed headspace
      (RHS) analysis for measuring of matrix effects and their use for identification
      and characterization of condensed matrices such as pharmaceuticals, polymers,
      chromatographic packing, etc. applicable for both quality control monitoring and
      research and development investigation. In RHS methods, the matrix is spiked and
      equilibrated with a mixture of volatile chemicals containing various functional
      groups (molecular sensor array or MSA mixture). Headspace chromatograms of the
      same spikes of a sample and an empty vial are compared. Examination of basic
      headspace theory shows that matrix specific constants (M), rather than partition
      coefficients (K), can be calculated from the headspace chromatograms and M=(K
      1)xbeta, where beta is a degree of matrix volume change during equilibration.
      Matrix specific constants can be plotted against any property of chemicals
      (polarity, dielectric constant, solubility parameter, vapor pressure, etc.) or
      just against a set of consecutive numbers, each representing a chemical in MSA.
      This plot is, in a sense, a molecular affinity spectrum (MAS) specific for a
      given matrix at a given temperature and is independent of an instrument. Changes
      in MAS that correspond to chemicals with a particular functional group give an
      insight to the type of differences between matrices and may quantitatively define
      them.

PMID- 16620508
TI  - Challenges in the analytical method development and validation for an unstable
      active pharmaceutical ingredient.
AB  - A sensitive high-performance liquid chromatography (HPLC) impurity profile method
      for the antibiotic ertapenem is developed and subsequently validated. The method
      utilizes an Inertsil phenyl column at ambient temperature, gradient elution with
      aqueous sodium phosphate buffer at pH 8, and acetonitrile as the mobile phase.
      The linearity, method precision, method ruggedness, limit of quantitation, and
      limit of detection of the impurity profile HPLC method are found to be
      satisfactory. The method is determined to be specific, as judged by resolving
      ertapenem from in-process impurities in crude samples and degradation products
      that arise from solid state thermal and light stress, acid, base, and oxidative
      stressed solutions. In addition, evidence is obtained by photodiode array
      detection studies that no degradate or impurity having a different UV spectrum
      coeluted with the major component in stressed or unstressed samples. The
      challenges during the development and validation of the method are discussed. The
      difficulties of analyzing an unstable active pharmaceutical ingredient (API) are
      addressed. Several major impurities/degradates of the API have very different UV
      response factors from the API. These impurities/degradates are synthesized or
      prepared by controlled degradation and the relative response factors are
      determined.

PMID- 16620509
TI  - Determination and characterization of the pyrolysis products of isoprocarb by GC
      MS.
AB  - The pyrolysis behavior of isoprocarb (an insecticide with contact and stomach
      action) is investigated using pyrolysis-gas chromatography-mass spectrometry. The
      pyrolysis products are separated using an HP-5 column under temperature program
      with helium as the carrier gas. The total of 80 separated pyrolysis components at
      600 degrees C, 750 degrees C, and 900 degrees C under helium atmosphere are
      identified using a probability-based matching search procedure, combined with the
      correlation of boiling point (BP) and Lee retention index (RI). Some of the BP
      values of the tentative components are estimated using the group contributions
      method because experimental values are not available. The levels of the
      identified components are estimated by the peak area normalization method from
      the chromatogram. It is found that isoprocarb decomposes more with the increase
      of temperature, and a large number of mono aromatics and polycyclic aromatic
      hydrocarbons and their derivatives are produced when the pyrolysis temperature is
      higher than 750 degrees C. The content of the decomposition products in the
      pyrolysate varies from 0.04% to 22.20%.

PMID- 16620510
TI  - Prediction of gas chromatographic retention times of esters of long chain
      alcohols and fatty acids.
AB  - The linear free energy of solution (DeltaG) relationship (DeltaG=DeltaGo+zdeltaG)
      for compounds of different carbon atoms (z) in the same homologous series is
      expanded and modified to cover compounds with two different hydrocarbon side
      chains. The expanded equation is successfully used to predict the retention times
      (tR) of standard esters of long chain alcohols and fatty acids of different chain
      lengths in both isothermal and temperature-programmed gas chromatography (TPGC).
      Approximately 90% of the 125 predicted tR values have a difference of less than
      1.00% from the actual tR and the highest difference is 1.26%. Two different
      temperature gradients in TPGC are tested. The expanded equation can be used to
      forecast the tR of TPGC with good accuracy. The highest difference is +/-1.40%
      and +/-1.00% for the temperature gradients of 2 degrees C and 4 degrees C/min,
      respectively. However, the increments in free energy per carbon atom (zdeltaG) of
      the alcohol and acid are approximately equal but have slightly different
      temperature sensitivities. Therefore, it is very difficult to separate esters of
      different acid and alcohol chain length but with the same total carbon numbers.
      Furthermore, the difference in temperature sensitivities for the acid and alcohol
      side chains renders them to be inversely eluted at different temperatures.

PMID- 16620511
TI  - Chromatographic and mass spectral studies on methoxymethcathinones related to 3,4
      methylenedioxymethamphetamine.
AB  - The methoxymethcathinones are uniquely regioisomeric with the controlled drug
      substance 3,4-methylenedioxymethamphetamine (3,4-MDMA) or Ecstacy. The various
      isomeric forms of the methoxymethcathinones have mass spectra essentially
      equivalent to 3,4-MDMA. They all have a molecular weight of 193 and major
      fragment ions in their electron ionization mass spectra at m/z 58 and 135/136.
      Differentiation by mass spectrometry was only possible after formation of the
      perfluoroacyl derivatives, pentafluoropropionylamides (PFPA), and
      heptafluorobutrylamides (HFBA). Gas chromatographic separation on nonpolar
      stationary phases successfully resolved the three methcathinones from 2,3- and
      3,4-MDMA as the PFPA and HFBA derivatives.

PMID- 16620512
TI  - Applications of deactivated GC columns for analysis of nitrogen-containing
      chemicals related to the chemical weapons convention.
AB  - Nitrogen-containing chemicals are one of the important families of compounds
      relevant to the purposes of the Chemical Weapons Convention (CWC). Several
      applications, using various injection modes, of new deactivated columns specially
      designed for basic compounds are presented. These columns prove remarkably well
      suited to the gas chromatographic (GC) analysis of the chemicals of interest,
      even to underivatized amino-alcohols, whose analysis on conventional GC columns
      is often difficult and hindered by poor resolution and high detection limits.
      Such a deactivated phase can even replace the typical GC phases used for CWC
      verification purposes.

PMID- 16620513
TI  - Analysis of the optical and geometrical isomer distributions in selected
      propylene glycol acetals.
AB  - For the first time, relative distributions of optical and geometrical isomers in
      selected propylene glycol acetals are determined. Resolution of the four acetal
      isomers possible through the reaction of racemic propylene glycol (PG) with
      selected aldehydes is demonstrated. The four isomers are ascribed to the presence
      of syn and anti geometrical isomers for each optically active PG acetal
      enantiomer. Thus, the (+) and well as (-) enantiomer are found to have a pair of
      syn and anti geometrical isomers. The ratio of the (+) and (-) isomers in the
      product remains at an approximate 50:50 ratio, as expected. However, somewhat
      unexpectedly, the syn/anti geometrical isomer ratio systematically varies with
      the nature of the substituent comprising the side chain of the aldehyde.
      Mechanisms involving electronic and minimal steric effects are advanced as
      possible reasons for the change in the syn/anti PG acetal ratios.

PMID- 16620514
TI  - Preparative high-performance liquid chromatographic separation of
      naphthodianthrones from St. John's Wort.
AB  - St. John's Wort (Hypericum perforatum), a perennial flowering plant, has been
      used medicinally for thousands of years and has most recently been identified as
      an effective treatment for mild to moderate depression and neuralgic disorders.
      This work presents a procedure for the isolation of naphthodianthrones from St.
      John's Wort by an accelerated extraction and separation of marker compounds by
      preparative high-performance liquid chromatography (HPLC) with photodiode array
      detection. The accelerated extraction method minimizes the extraction time and
      increases the yield, and the marker compounds obtained by preparative HPLC are of
      98% purity. The compounds are characterized by liquid chromatography-mass
      spectrometry (electrospray ionization) and NMR spectra.

PMID- 16620515
TI  - Bi-Langmuir isotherms' applicability for description of interaction of ion
      exchange sorbents with protein mixtures.
AB  - The sorption of a protein pair on carboxylic cation exchangers with various
      contents of ionogenic groups is examined. The bi-Langmuir isotherm calculation is
      carried out from sorption data for single-component systems. It is shown that
      good agreement of calculated and experimental data is reached only when protein
      sorbent interaction weakens because of implementation of the competitive sorption
      mechanism.

PMID- 16620516
TI  - Analysis of residual products in triethylbenzylammonium chloride by HPLC. Study
      of the retention mechanism.
AB  - The control of industrial products for minimization of their impact on the
      environment and human health requires the development of specific analysis
      methods. Information provided by these methods about toxic components, by
      products, and other derivatives may also be useful to reduce the possible impact
      of industrial products. The studied compound in this paper,
      triethylbenzylammonium chloride (TEBA), is mainly used in industrial synthesis.
      This quaternary compound and its residual products coming from quaternization
      reaction (benzyl chloride, benzaldehyde, and benzyl alcohol) are analyzed by
      HPLC. The separation is based on control of the silanophilic contribution to TEBA
      retention because of the quaternary nature of this compound. The effect of the
      three buffers (sodium acetate, ammonium acetate, and sodium formate) and their
      concentrations in the chromatographic behavior of the quaternary compound is
      examined. The buffer cation and anion regulate TEBA retention. Also, the
      concentration of the quaternary compound is another parameter that had influence
      in some aspects of its chromatographic behavior (e.g., retention and symmetry).
      The proposed method is applied to TEBA synthesis along, with the formation and
      removal of impurities with the results compared with those obtained for the
      quaternary compound benzalkonium chloride.

PMID- 16620517
TI  - Study on a new precolumn derivatization method in the determination of metformin
      hydrochloride.
AB  - Metformin hydrochloride is successfully determined by reversed-phase high
      performance liquid chromatography with a new precolumn derivatization method
      using 9,10-anthraquinone-2-sulfonyl chloride as the derivatization agent. Several
      derivatization systems are tried to optimize the derivatization conditions, and a
      new post-derivatization treatment method is established. The derivatization
      product is analyzed on a Lichrosper C18 column (6.0 mm x 150 mm, 5 microm) at 256
      nm with methanol-water (70:30, v/v) as the mobile phase. The calibration curves
      of the derivatives for the UV detector (0.01-4 mg/L) are linear with respect to
      peak area. The detection limit (peak area) for the metformin hydrochloride is
      0.01 mg/L for a signal-to-noise ratio of 3:1. In human plasma, the detection
      limit is 0.02 mg/L. This assay is rapid, sensitive, and highly reproducible.

PMID- 16620518
TI  - A gradient HPLC test procedure for the determination of impurities and the
      synthetic precursors in 2-[4-(1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1
      piperidinyl]-butyl)-phenyl]-2-methylpropionic acid.
AB  - A gradient high-performance liquid chromatographic (HPLC) test procedure is
      developed and evaluated for its ability to establish the levels of impurities and
      remaining synthetic precursors in 2-[4-(1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1
      piperidinyl]-butyl)-phenyl]-2-methylpropionic acid. A gradient program with a
      mobile phase of 0.02 M sodium phosphate buffer and 0.004 M sodium perchlorate in
      acetonitrile-water (approximately pH 2.5) is used with a Spherisorb C6 column.
      The acetonitrile composition is increased linearly from 40% to 65% over a 45-min
      period and held at 65% for 20 min. UV detection at 210 nm is used to quantitate
      all components. The procedure is validated for accuracy using spiked levels (0.1%
      to 1.5%, w/w) with two suspected impurities, the synthetic precursors. A multiday
      repeatability study using two different Spherisorb C6 columns and HPLC systems
      shows consistent impurity quantitation results with one production lot of the
      bulk compound.

PMID- 16620519
TI  - Determination of the newer quinolones levofloxacin and moxifloxacin in plasma by
      high-performance liquid chromatography with fluorescence detection.
AB  - A simple, accurate, sensitive, and precise reversed-phase (RP) high-performance
      liquid chromatographic (HPLC) method with fluorescence detection allowing the
      sensitive and specific quantitation of the newer fluoroquinolones levofloxacin
      and moxifloxacin is described. Moxifloxacin is used as the internal standard for
      the determination of levofloxacin and vice versa. A single-step liquid-liquid
      extraction from human plasma is sufficient for both quinolones. The method is
      linear from 0.1 to 15 microg/mL and 0.2 to 7 microg/mL for levofloxacin and
      moxifloxacin, respectively, covering the clinically relevant plasma concentration
      range. The limits of quantitation are 0.05 microg/mL (levofloxacin) and 0.2
      microg/mL (moxifloxacin). The method is successfully applied to plasma drug level
      monitoring in a volunteer receiving single therapeutic doses of levofloxacin or
      moxifloxacin at two different occasions.

PMID- 16620520
TI  - Improved real-time puff-by-puff GC-MS system for whole smoke analysis.
AB  - An automated puff-by-puff mainstream smoke (MSS) system is developed to monitor
      real-time whole smoke in mainstream cigarette smoke using gas chromatography (GC)
      mass spectrometry (MS). The whole-smoke analysis is based on automated sample
      collection and injection into the GC-MS system. The important feature of this
      system is the real-time rapid analysis that is simple, sensitive, precise,
      flexible, and exhibits low carryover of volatile and semivolatile smoke
      constituents. The system is equipped with an automated sampling and switching
      valve and a smoking machine. The key improvements of the system, as compared with
      current and alternative methodologies, include minimizing variations caused by
      operator sampling techniques, the real-time analysis of MSS, the detection of
      flavorants in MSS from a single puff of cigarette smoke, the ability to analyze
      numerous smoke constituents from either whole smoke or the gas phase of a single
      puff, the ability to monitor a few selected smoke constituents in whole smoke
      using multiple puffs, and its good feasibility compared with solvent extraction
      and impinger trapping procedures for volatile organic compounds in MSS. System
      configuration and sampling methodologies are described. Sensitivity, flexibility,
      precision, feasibility, carryover, and applications of the system are discussed.

PMID- 16620521
TI  - Monitoring the metabolism of moexipril to moexiprilat using high-performance
      liquid chromatography-electrospray ionization mass spectrometry.
AB  - High-performance liquid chromatography combined with a UV absorbance detector and
      electrospray ionization mass spectrometer is used for the simultaneous analysis
      of moexipril and moexiprilat in biological samples. Moexipril and moexiprilat are
      determined in samples metabolized by rat and human liver microsomal preparations,
      and also in rat urine. The calibration curve is linear in the ng/mL and microg/mL
      concentration range of the injected moexipril.

PMID- 16620522
TI  - Stacked injection with low thermal mass gas chromatography for PPB level
      detection of oxygenated compounds in hydrocarbons.
AB  - The presence of oxygenated compounds in light hydrocarbons can have a negative
      impact in manufacturing processes and on the quality of products produced. The
      development of an analytical technique termed "stacked injection" has been
      reported earlier. With this technique, sensitivity in the parts-per-billion (ppb)
      range for oxygenated compounds can be achieved, even with a flame ionization
      detector; however, there are drawbacks for this approach that limit its overall
      effectiveness. A new, improved analytical technique has been developed that not
      only addresses the shortcomings encountered, but offers markedly higher
      analytical performance. The new concept employs multidimensional gas
      chromatography (GC) with low thermal mass GC. With this new approach, throughput
      improvements of up to 5 times, range extension of solutes amenable for this
      analysis of up to nC16 alcohol, and ppb levels of detection for oxygenated
      compounds are achieved. Apart from alcohols, this technique is successfully
      employed for the ppb level analysis of other classes of oxygenated compounds,
      such as ethers, aldehydes, and aromatics.

PMID- 16620523
TI  - Determination of geniposide in rat urine after oral administration of the
      traditional Chinese medicinal preparation yin-zhi-ku decoction by high
      performance liquid chromatography.
AB  - A high-performance liquid chromatography method with solid-phase extraction is
      introduced for the determination of geniposide in rat urine after oral
      administration of yin-zhi-ku decoction. Geniposide and an internal standard
      (paeoniflorin) are extracted from urine using Strata cartridges. Analysis of the
      extract is then performed on a reversed-phase C18 column using acetonitrile-water
      (14:86, v/v) as eluting solvent system. UV detection is set at 238 nm. The
      calibration curve for geniposide is linear (r = 0.9996) in the concentration
      range of 2.0-240 microg/mL. Both intra- and interday precision of the geniposide
      are determined, and their relative standard deviation does not exceed 10%. The
      validated method is successfully applied to determine geniposide from rat urine
      after oral administration of yin-zhi-ku decoction.

PMID- 16620524
TI  - Evidence of morphine metabolism to hydromorphone in pain patients chronically
      treated with morphine.
AB  - Minor metabolic pathways in human subjects have been shown to exist for the
      conversion of codeine to hydrocodone but have not been reported for the metabolic
      conversion of morphine to hydromorphone. In this study, urine specimens were
      collected in an out-patient setting from 13 pain patients who were chronically
      treated with morphine and other opioids (methadone, oxycodone, and fentanyl). The
      chronic pain patients were chosen for study because they were treated with high
      dose morphine and had no personal or family history of addiction. Results of the
      initial evaluation and follow up of these patients with random urine tests did
      not indicate opioid misuse. The specimens were analyzed by GC-MS for the presence
      of hydromorphone. The reporting limit for hydromorphone was 100 ng/mL. Ten of the
      13 morphine-treated patients excreted hydromorphone in minor amounts ranging 120
      to 1400 ng/mL. Concurrent morphine concentrations were exceedingly high in these
      10 patients and frequently exceeded the upper limit of linearity (> 10,000 ng/mL)
      of the assay. The ratio of hydromorphone to morphine ranged from 0.015 to 0.024.
      Morphine concentrations in the three patients in which hydromorphone was not
      detected tended to be lower than those observed in other patients. For
      comparison, one additional patient was included in the study, who was prescribed
      both morphine and hydromorphone. Concentrations of hydromorphone in this patient
      were in the range of 3400-13,000 ng/mL, while concurrent morphine concentrations
      were in the range of 3200-6600 ng/mL. These data are highly suggestive that
      hydromorphone can be produced as a minor metabolite of morphine in humans.
      Although additional studies in more restricted settings are needed, it is
      recommended that interpretation of low urinary concentrations of hydromorphone in
      combination with high concentrations of morphine in morphine-treated pain
      patients should not be considered as conclusive evidence of hydromorphone misuse.

PMID- 16620525
TI  - Analysis of diacetylmorphine, caffeine, and degradation products after
      volatilization of pharmaceutical heroin for inhalation.
AB  - Pharmaceutical smokable heroin was developed for a clinical trial on medical co
      prescription of heroin and methadone. This product, consisting of 75% w/w
      diacetylmorphine base and 25% w/w caffeine anhydrate, was intended for use via
      "chasing the dragon", that is, inhalation after volatilization. This procedure
      involves heating the powder mixture, which may lead to formation of degradation
      products that could subsequently be inhaled. We developed a method that used a
      high-performance liquid chromatography system that was compatible with photodiode
      array detection and mass spectrometric detection to separate diacetylmorphine-
      and caffeine-related compounds in a wide polarity range for analysis of the
      vapor. This method was used to analyze the contents of the plastic drinking
      straws that were used by patients to inhale the vapors from pharmaceutical heroin
      used via chasing the dragon, which were considered to be representative of the
      vapors the patients inhaled. They contained primarily unchanged diacetylmorphine,
      its main metabolite 6-acetylmorphine, caffeine, and some morphine. Several
      unidentified peaks were observed in the straw chromatograms. Chemical structures
      were proposed for nine degradation products: morphine derivatives with different
      substitution patterns of the C(3), C(6), and/or N(17) positions, which comprised
      0.4-9.7% of the straw sample residue weight. Activity and toxicity of most of
      these compounds are unknown and require further investigation.

PMID- 16620526
TI  - Quantitative determination of sildenafil (Viagra) and its metabolite (UK-103,320)
      in fluid and tissue specimens obtained from six aviation fatalities.
AB  - During the investigation of aviation accidents, postmortem samples from victims
      are submitted to the Federal Aviation Administration's Civil Aerospace Medical
      Institute for toxicological analysis. This report presents a rapid and reliable
      method for the identification and quantitation of sildenafil (Viagra) and its
      active metabolite, UK-103,320. This procedure utilizes sildenafil-d(8) as an
      internal standard for more accurate and reliable quantitation. The quantitation
      of sildenafil and UK-103,320 in postmortem fluid and tissue specimens obtained
      from victims from six separate aviation fatalities is described. The method
      incorporates solid-phase extraction and liquid chromatography-tandem mass
      spectrometry (LC-MS-MS) and MS-MS-MS utilizing an atmospheric pressure chemical
      ionization ion trap MS in the positive chemical ionization mode. Solid-phase
      extraction provided an efficient sample extraction yielding recoveries ranging
      from 79 to 88%. The limits of detection for sildenafil and UK-103,320 were 0.39
      and 0.19 ng/mL, respectively. The linear dynamic range for both compounds was
      0.78-800 ng/mL. The current method proved to be simple, accurate, and robust for
      the identification and quantitation of sildenafil and UK-103,320 in postmortem
      fluids and tissues.

PMID- 16620527
TI  - Rapid determination of N,N-diethyl-m-toluamide and permethrin in human plasma by
      gas chromatography-mass spectrometry and pyridostigmine bromide by high
      performance liquid chromatography.
AB  - A rapid and highly sensitive gas chromatography-mass spectrometry (GC-MS) method
      for simultaneous determination of N,N-diethyl-m-toluamide (DEET) and permethrin
      with (2)H(10)-phenanthrene (98 atom %) as an internal standard and a separate
      external standard high-performance liquid chromatography (HPLC) method for
      pyridostigmine bromide (PB) determination in human plasma were developed and
      validated. The GC-MS method for DEET and permethrin quantification utilizes a one
      step extraction with tert-butylmethylether. The HPLC method for PB quantification
      involves a solid-phase extraction and UV detection. The range of the analytical
      method for DEET and permethrin was 1 ng/mL to 100 ng/mL and for PB was 5 ng/mL to
      100 ng/mL. Recovery from plasma proved to be more than 80%. The intraday
      precision ranged from 1.3% to 8% for DEET, from 2.1% to 11.4% for permethrin, and
      from 3.0% to 4.8% for PB. The interday precision was 3% for DEET, ranged from 5%
      to 9% for permethrin, and from 5% to 9% for PB. The accuracy for the limit of
      quantification was 92% +/- 8% relative standard deviation (RSD) for DEET, 112% +/
      11% RSD for permethrin, and 109% +/- 5% RSD for PB. All 3 compounds were stable
      in human plasma at -80 degrees C for at least 12 months and after 2 freeze-thaw
      cycles with RSD values ranging from 7.1% (DEET, 80 ng/mL) to 8.1% (DEET, 8
      ng/mL), from 2.3% (permethrin, 80 ng/mL) to 11.6 % (permethrin, 8 ng/mL), and
      from 0.2% (PB, 80 ng/mL) to 3.6% (PB, 8 ng/mL). Both methods were successfully
      applied to pharmacokinetic/ pharmacodynamic studies of combined exposure of DEET
      (skin application), permethrin (treated uniforms), and PB (30 mg orally three
      times/day for four doses) in healthy volunteers (n = 81).

PMID- 16620528
TI  - Drug monitoring and toxicology: a procedure for the monitoring of levetiracetam
      and zonisamide by HPLC-UV.
AB  - This article describes a rapid isocratic high-performance liquid chromatographic
      (HPLC) method for the simultaneous measurement of the anticonvulsants
      levetiracetam and zonisamide. Monitoring these drugs is important for detecting
      potentially toxic concentrations, particularly in patients with renal impairment,
      but no commercial assays are currently available. Following a liquid-liquid
      extraction, levetiracetam (5-150 microg/mL) and zonisamide (5-80 microg/mL) are
      quantitated by HPLC-UV. The assay's limit of quantitation, linearity,
      imprecision, and accuracy adequately cover the therapeutic range of these drugs.
      The assay should be attractive to clinical laboratories because the run time for
      quantification of both drugs is approximately 5 min per sample, and no
      interferences are currently known.

PMID- 16620529
TI  - Determination of benzodiazepines in human urine using solid-phase extraction and
      high-performance liquid chromatography-electrospray ionization tandem mass
      spectrometry.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS-MS) method has been
      developed and validated for the determination of benzodiazepines, on the market
      in Norway, and/or their metabolites in human urine. The following compounds were
      included: 7-aminonitrazepam, 7-aminoclonazepam, 7-aminoflunitrazepam, alprazolam,
      alpha-hydroxyalprazolam, oxazepam, 3-OH-diazepam, and n-desmethyldiazepam. The
      method includes hydrolysis of urine samples (0.5 mL) with beta-glucuronidase at
      60 degrees C for 2 h before solid-phase extraction with a polymer-based mixed
      mode column. The analytes were quantified in multiple reaction monitoring mode
      using two transitions. Deuterated analogues were used as internal standards for
      all analytes except 7-aminonitrazepam and alpha-hydroxyalprazolam, which were
      quantified using 7-aminoclonazepam-d(4) and alprazolam-d(5), respectively. The
      concentration range was 0.1-8.0 microM for 7-aminonitrazepam, 7-aminoclonazepam,
      7-aminoflunitrazepam, alprazolam, and alpha-hydroxyalprazolam and 0.5-40 microM
      for the other compounds. The average recovery for the different analytes ranged
      from 56% to 83%. The between-day precision of the method was in the range of 3
      12%. The limits of quantification were found to be between 0.002 and 0.01 microM
      for the different compounds. Comparison with other analytical methods was
      performed for method validation, using approximately 500 samples provided by the
      routine laboratory at the Norwegian Institute of Public Health. The LC-MS-MS
      method has proven to be robust and specific for the determination of
      benzodiazepines in urine. It has been routinely used for approximately 1800
      samples in the past 7 months.

PMID- 16620530
TI  - Metabolism and the urinary excretion profile of the recently scheduled designer
      drug N-Benzylpiperazine (BZP) in the rat.
AB  - The metabolism of N-benzylpiperazine (BZP), a recently scheduled designer drug,
      in the rat has been studied by analyzing its urinary metabolites. p-Hydroxy-BZP
      (p-OH-BZP) was unequivocally identified as the main metabolite along with a minor
      metabolite m-hydroxy-BZP (m-OH-BZP), using gas chromatography-mass spectrometry
      and high-performance liquid chromatography-electrospray ionization mass
      spectrometry (LC-ESI MS). The time-course excretion profiles of BZP, p-OH-BZP,
      and m-OH-BZP in the rats were investigated after a single intraperitoneal dosing
      of 5 mg/kg BZP, by using an optimized analytical procedure that combines solid
      phase extraction and LC-ESI MS determination. The cumulative amounts excreted
      within the first 48 h were approximately 25% for p-OH-BZP and 2% for m-OH-BZP,
      whereas 6.7% dose of the parent drug BZP was excreted unchanged within 36 h post
      dosing. The concentration ratio of p-OH-BZP to m-OH-BZP was 11.6 in the first 4
      h, but it increased to 22.7 in 48 h with the elapsed time post-dosing. Most of p
      OH-BZP was excreted in urine within approximately 36 h post-dosing, with
      approximately 50% appearing as the glucuronide conjugate. The present results
      suggest that p-OH-BZP is the most relevant metabolite to be detected for the
      proof of BZP intake in the forensic and clinical analysis of human urine.

PMID- 16620531
TI  - Evaluation of solid-phase sorbents for the analysis of ropinirole in whole blood.
AB  - In this paper, the extraction and analysis of ropinirole from whole blood using
      solid-phase cartridges is presented. Previously published methods for the
      analysis of this drug have employed plasma samples using C(18) cartridges. Liquid
      liquid extraction has been employed for analysis of postmortem samples. In the
      method, drug free blood was spiked with ropinirole (0 to 10 ng) and an internal
      standard (quinidine). The samples were buffered with distilled water and
      centrifuged. The supernatant liquid was applied to previously conditioned
      endcapped C(6), C(18), and C(8)/SCX solid-phase extraction columns. The columns
      were washed, dried, and eluted with various solvents systems. The eluants were
      collected and evaporated. The residue was dissolved in 100 microL of aqueous 0.1%
      trifluoroacetic acid and analyzed by liquid chromatography using a C(18) (4.6 x
      150 mm, 5-microm particle size) column and monitored at 250 nm, using diode-array
      detection. A mobile phase consisting of methanol/0.1% TFA in distilled water
      (22:78 v/v) was employed. The data was collected and appraised. It was found that
      3-mL 200-mg CEC06 C6 (Hexyl endcapped) solid-phase columns that had been washed
      with 3 x 3 mL water and 3 x 3 mL acetonitrile and eluted with a solvent system
      consisting of 95:5 v/v acetonitrile/ammonia performed best. The linear range for
      this analysis was found to be from 0 to 10 ng/mL. The limit of detection was
      determined to be 1 ng/mL with a limit of quantification of 2.5 ng/mL.

PMID- 16620532
TI  - A comparative evaluation of the instant-view 5-panel test card with OnTrak
      TesTcup Pro 5: comparison with gas chromatography-mass spectrometry.
AB  - This study compared the ability of two on-site testing devices, Instant-View Test
      Card and OnTrak TesTcup Pro 5, to discriminate negative from positive urine
      samples for cannabinoids, cocaine metabolite, opiates, amphetamines, and
      benzodiazepines. The on-site devices were evaluated in a precision study with
      fortified urine samples and in a clinical study with samples submitted for
      forensic urine drug testing. For precision, seven stocks were prepared per
      device. Each stock had all five analytes added in a random fashion at 0, 25, 50,
      75, 125, 150, or 175% of cutoff. Ten aliquots per stock were assigned random
      numbers and analyzed by two individuals. The respective accuracies (defined as "%
      below cutoff samples that were negative + % above cutoff samples that were
      positive") for Instant-View Test Card and TesTcup were 74.3 and 87.1 for
      amphetamines; 82.1 and 90.7 for benzoylecgonine; 88.6 and 90.7 for
      benzodiazepines; 83.6 and 94.3 for morphine; 82.1 and 87.9 for cannabinoids; and
      82.1 and 90.1% overall. In contrast to the on-site testing devices, instrumental
      testing with OnLine reagents had perfect precision. For the clinical study,
      submitted samples that had reached their disposal date were rescreened for the
      five drug groups. Fifty that had absorbance changes near the negative control for
      all five drug groups were selected as "negatives"; 240 samples with positive or
      multi-positive results (some between the 75% control and cutoff) and confirmed by
      GC-MS were chosen as "positives" (at least 45 per drug group). The non-positive
      drug groups in these samples added 150 additional presumptively negatives per
      drug group. Samples were assigned random numbers, and two individuals tested each
      sample. The respective accuracies in respect to GC-MS results for Instant-View
      Test Card and TesTcup were 95.8 and 91.7 for amphetamines; 100 and 100 for
      benzoylecgonine; 96.7 and 96.5 for benzodiazepines; 98.8 and 99.2 for opiates;
      94.4 and 95.0 for cannabinoids; and 97.1 and 96.5% overall. The clinical study
      revealed that the Instant-View Test Card had low cross-reactivity (i.e., false
      negatives) for samples with amphetamine only and oxycodone. TesTcup had low cross
      reactivity for samples with amphetamine only and hydrocodone and/or
      hydromorphone; it also had more cross-reactivity towards (i.e., false positives)
      sympathomimetic amines. In summary, the Instant-View Test Card was less precise
      than the TesTcup at or near the cutoff; with clinical samples, however, the
      percent accuracies of the two devices were similar.

PMID- 16620533
TI  - Qualitative identification of doxacurium and its breakdown products in postmortem
      fluids by liquid chromatography-tandem mass spectrometry.
AB  - During a death investigation at the Office of the Cuyahoga County Coroner in
      Cleveland, OH, doxacurium became a drug of interest. The Coroner's Office
      enlisted the aid of the Federal Bureau of Investigation Laboratory for the
      doxacurium analysis. Following the request, a method for the extraction and
      qualitative analysis of the drug in biological fluids was developed. The
      procedure relies on a simple solid-phase extraction procedure followed by
      qualitative analysis with liquid chromatography-tandem mass spectrometry. During
      the development of the new analytical procedure, two breakdown products of
      doxacurium were detected. Structures for these breakdown products are proposed.
      This procedure was used to analyze heart blood, cerebrospinal fluid, and bile
      specimens from the decedent. Doxacurium and its breakdown products were
      identified in all three specimens.

PMID- 16620534
TI  - Performance characteristics of DRI, CEDIA, and REMEDi systems for preliminary
      tests of amphetamines and opiates in human urine.
AB  - Arrestee urine specimens (930) were tested with DRI, CEDIA, and REMEDi; those
      that tested positive for amphetamines and opiates (616 and 414, respectively)
      were then confirmed by gas chromatography-mass spectrometry. The performance
      characteristics of these three preliminary systems were evaluated using the
      following commonly used parameters: true positive, true negative, false positive,
      and false negative. The sensitivity, specificity, and efficiency of these methods
      were also calculated. Data derived from this study indicated DRI and CEDIA
      adapted by this study generated acceptable preliminary test results for
      amphetamine/methamphetamine and morphine/codeine, but not for MDA/MDMA and REMEDi
      has lower sensitivity than DRI and CEDIA, but with better specificity and
      efficiency, supporting its use under emergency room settings where drug
      concentrations in overdose cases are expectedly at high levels.

PMID- 16620535
TI  - Paradoxical results in urine drug testing for 6-acetylmorphine and total opiates:
      implications for best analytical strategy.
AB  - A major task in urine drug testing is to detect heroin intake. The most common
      way of doing this is by using morphine as the analytical target in opiate
      immunoassay screening. However, this strategy sometimes leads to false-positive
      results because morphine is not a metabolite unique to heroin. The objective of
      this study was to evaluate the usefulness of the unique heroin metabolite 6
      acetylmorphine (6-AM) as the primary analytical target in combination with
      morphine in the screening assay. A total number of 3521 randomly collected urine
      samples from 707 patients undergoing heroin substitution treatment were
      investigated for 6-AM and opiates by CEDIA (cloned enzyme donor immunoassay) and
      for opiates by DRI immunoassays and by gas chromatography-mass spectrometry (free
      6-AM, free morphine, total morphine, and total codeine). The rate of positive
      outcome in the screening for 6-AM was 9.1% (cutoff 10 microg/L), and for opiates,
      it was 22.6% (cutoff 300 microg/L), which is in accordance with a known shorter
      detection time for 6-AM following heroin intake. However, by comparing 6-AM and
      opiate screening results at different cutoff levels, it was observed that 7-8% of
      the samples and 12.5% of the patients with detectable 6-AM had an unexpected low
      content of free and total morphine in the urine. This study confirms earlier
      observations that certain individuals may escape detection in urine drug testing
      when morphine is being utilized for the detection of heroin intake. The
      underlying mechanism for this may be a metabolic defect and/or interaction. It is
      concluded that 6-AM is a valuable target analyte in the screening of drugs of
      abuse in urine and may be used in combination with opiate screening in clinical
      testing.

PMID- 16620536
TI  - Elevated urine arsenic: un-speciated results lead to unnecessary concern and
      further evaluations.
AB  - The consumption of seafood within two to three days of testing can increase total
      urine arsenic concentrations. Few clinicians are familiar with this fact and
      often misinterpret elevated results. A retrospective chart review of all cases
      with arsenic testing seen between 1991 and 2004 at an occupational and
      environmental medicine referral clinic was performed. Urine arsenic results were
      classified as follows: total arsenic levels; speciated results (inorganic, ionic
      arsenic); and whether the patient abstained from seafood prior to the collection.
      Laboratory detection limits for total and for ionic arsenic were < or = 2
      microg/L. Fifty-four patients with urine arsenic testing were identified. The
      total urine arsenic concentration exceeded 40 microg/L for 28 patients. On
      paired, speciated testing (n = 21), mean total arsenic was 122 +/- 227 microg/L,
      and ionic arsenic was not detected in any of these same samples (p = 0.023). On
      paired testing, before and after seafood abstention (n = 12), total urine arsenic
      without abstention was 291 +/- 267 microg/L, and it was only 9 +/- 12 microg/L
      after seafood abstention (p = 0.004). The total urine arsenic elevations observed
      in our series were due to benign organic arsenic compounds commonly found in
      seafood. Laboratories should reflexively perform speciation on most samples with
      elevated total arsenic concentrations prior to reporting the results. Reflexive
      speciation could reduce unnecessary referrals, further testing, and patient
      anxiety.

PMID- 16620537
TI  - Analysis of ingested material and urine by GC-MS and 1H NMR spectroscopy:
      poisoning of an adult with adulterated soda.
AB  - The purpose of this work is to characterize chemical compounds added to an
      ingested soda by (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy and by
      gas chromatography-mass spectrometry in the electron impact mode. A second point
      was to highlight possible metabolic disturbances by considering urinary profile.
      Without any pretreatment, dimethylphtalate, 2-butanone, and 2,2,4
      trimethylpentanediol diisobutyrate were found in the adulterated soda.
      Quantitative analysis was performed by relative integration of peak areas. Huge
      quantities of 2,2,4-trimethylpentanediol diisobutyrate and dimethylphtalate were
      found in the oily layer. 2-Butanone, which is miscible in water, was found in the
      two phases as well as small quantities of dimethylphtalate. The urine sample was
      collected on hospital admission and was also analyzed by (1)H NMR spectroscopy.
      The major abnormal compound found was 1,2-propanediol. Other disturbances
      concerned endogenous metabolites such as 2-ketoglutaric acid, lactic acid, and
      betaine.

PMID- 16620538
TI  - Investigative implications of the instability and metabolism of mebeverine.
AB  - The anti-spasmodic drug mebeverine is used in the treatment of irritable bowel
      syndrome. It has been found to be unstable and rapidly metabolized to initially
      form mebeverine-alcohol and veratric acid. Mebeverine-alcohol is a precursor for
      a number of amphetamine-like compounds. Consequently, these, in addition to
      mebeverine and mebeverine-alcohol, can produce false-positive amphetamine
      immunoassay results. Mebeverine is highly unstable in esterase-containing
      biological fluid (in particular blood and plasma), but it is largely stable in
      aqueous solutions and urine. Sodium fluoride did not appear to reduce mebeverine
      breakdown. Because of its unstable nature, mebeverine analysis should be
      performed as soon as possible after specimen receipt. Mebeverine, mebeverine
      alcohol, and veratric acid concentrations should be measured in the blood/serum
      to assist interpretation; however, because of rapid metabolism/instability,
      mebeverine itself is rarely detected. In one fatal case of suspected mebeverine
      overdosage, mebeverine (1.2 mg/L), mebeverine-alcohol (74 mg/L), and veratric
      acid (127 mg/L) concentrations were measured in the postmortem blood; a high
      concentration of citalopram was also detected. In two fatalities involving
      possible therapeutic use, no mebeverine was detected, but mebeverine-alcohol (6.9
      and 5.4 mg/L) and veratric acid (13.7 and 41.8 mg/L) were found by gas
      chromatography-mass spectrometry and high-performance liquid chromatography-diode
      array detection (HPLC-DAD) and measured by HPLC-DAD. Only one case involving
      mebeverine has previously been published; this paper provides additional data and
      suggestions of best practice for case investigation.

PMID- 16620539
TI  - A comprehensive study on the variations in urinary concentrations of endogenous
      gamma-hydroxybutyrate (GHB).
AB  - This study was designed to supplement previous attempts to establish an accurate
      range of normal endogenous gamma-hydroxybutyrate (GHB) concentrations in random
      antemortem urine samples. Furthermore, its purpose was to ascertain the effect of
      gender, race, age, medications, and select medical conditions on endogenous
      concentrations of GHB in urine and the proposed endogenous urinary GHB cutoff of
      10 microg/mL. Urine samples (n = 207) were provided by subjects who reported that
      they had never used GHB. As part of the collection process, subjects also
      completed a short survey to collect information about gender, race, age, orally
      ingested medications, and select medical conditions. All specimens were analyzed
      in duplicate for the presence of endogenous GHB using a previously reported
      headspace gas chromatography-mass spectrometry method. The data were analyzed for
      tendencies among different population groups. GHB concentrations ranged from 0.00
      to 2.70 microg/mL in all specimens, with a median concentration of 0.24
      microg/mL. Males (n = 130) had an average endogenous GHB concentration of 0.27
      microg/mL (0.00-2.70 microg/mL), whereas females (n = 77) averaged 0.29 microg/mL
      (0.00-0.98 microg/mL). Select medical conditions and participants' race, age
      ranges, and medications that were used within 48 h prior to collection were also
      evaluated. We believe this to be the most comprehensive study on endogenous GHB
      concentrations in urine to date. The results of this study will aid the
      interpretation of low GHB concentrations measured in urine samples, particularly
      in investigations of drug-facilitated crimes.

PMID- 16620540
TI  - Pharmacogenomics for the forensic toxicologist.
AB  - Pharmacogenomics is the study of the linkage between an individual's genotype and
      the disposition of drugs in the body. The first association between adverse drug
      reactions and inherited variations was recognized in the 1950s, and since then,
      pharmacogenomics has come a long way. The importance of pharmacogenomics is
      accentuated by the incidence of adverse drug reactions, which may account for
      hospital expenditures of up to 5.6 billion dollars annually. Interindividual
      variations in drug metabolism are often the result of genetic variants or genetic
      polymorphisms, and polymorphisms have been known to alter the relationship
      between dose and plasma drug concentration. Drug disposition can be affected by
      polymorphisms in drug metabolizing enzymes, drug transport proteins, and drug
      targets. The cytochrome P450 (CYP) enzymes are responsible for the metabolism of
      a large number of drugs. Polymorphisms of the CYP enzymes have been well
      documented, and CYP2D6 is the most polymorphic CYP enzyme. However, there is a
      relative dearth of research on the role of transport proteins and drug targets.
      This review attempts to provide a brief synopsis of the pharmacogenomics of some
      common drug-metabolizing enzymes, transport proteins, and targets. The examples
      of tramadol, methadone, and oxycodone are used to illustrate the potential role
      of pharmacogenomics in forensic toxicology. Pharmacogenomics may present a
      practicable hypothesis in cases of incongruence between dose and plasma drug
      concentration, and the possibility of genotype-mediated drug plasma levels needs
      to be considered.

PMID- 16620541
TI  - Comparison of an automated and point-of-care immunoassay to GC-MS for urine
      oxycodone testing in the clinical laboratory.
AB  - OxyContin, a controlled-release formulation of oxycodone, is increasingly abused.
      Monitoring patient compliance by urine drug testing may deter illegal diversion
      of OxyContin. Two urine immunoassays were evaluated with a 100 ng/mL cutoff for
      oxycodone. The Microgenics Corporation Oxycodone DRI on the Bayer ADVIA 1650 and
      a point-of-care (POC) immunoassay, Monitect Oxycodone POC from Branan Medical
      Corporation, were compared to gas chromatography-mass spectrometry (GC-MS) with a
      detection limit of 50 ng/mL free oxycodone. Between-day precision for DRI yielded
      coefficients of variation from 3.9% to 7.0% at 75 and 125 ng/mL. Fifty-two
      positive and 52 negative urines were tested. The DRI had a 100% agreement with GC
      MS. Two positive specimens had free oxycodone < 50 ng/mL, but oxycodone
      metabolites, oxymorphone and oxycodone glucuronide > 100 ng/mL, were identified
      by GC-MS analysis. The POC assay had two false positives and 15 indeterminate (+/
      ) results. Codeine or hydrocodone was present in all but one of these samples.
      There was no interference with DRI from morphine, codeine, hydrocodone,
      hydromorphone, dihydrocodeine, or 6-monoacetyl morphine. Four-hundred and ninety
      urine samples were subsequently tested with DRI to estimate the oxycodone
      positive rate at our hospital, and 47 (9.4%) were positive. The confirmation rate
      with GC-MS for free oxycodone, not including metabolites, was 93%. The
      Microgenics DRI offers good performance for oxycodone urine testing and is a
      better choice for the clinical laboratory than the POC assay. Confirmation of
      screened positive samples requires a method that can detect total oxycodone and
      oxymorphone.

PMID- 16620542
TI  - Caffeine content of energy drinks, carbonated sodas, and other beverages.
AB  - The caffeine content of 10 energy drinks, 19 carbonated sodas, and 7 other
      beverages was determined. In addition, the variability of the caffeine content of
      Coca-Cola fountain soda was evaluated. Caffeine was isolated from the samples by
      liquid-liquid extraction and analyzed by gas chromatography with nitrogen
      phosphorus detection. The caffeine concentration of the caffeinated energy drinks
      ranged from none detected to 141.1 mg/serving. The caffeine content of the
      carbonated sodas ranged from none detected to 48.2 mg/serving, and the content of
      the other beverages ranged from < 2.7 to 105.7 mg/serving. The intra-assay mean,
      standard deviation, and % coefficient of variation for the Coca-Cola fountain
      samples were 44.5, 2.95, and 6.64 mg/serving, respectively.

PMID- 16620543
TI  - Validation of the Immunalysis microplate ELISA for the detection of buprenorphine
      and its metabolite norbuprenorphine in urine.
AB  - The purpose of this study was to validate the Immunalysis Buprenorphine
      Microplate enzyme-linked immunosorbent assay (ELISA) for the detection of
      buprenorphine in urine samples. Sixty-nine urine samples were obtained from
      volunteers on the Subutex treatment program and from routine samples submitted to
      the laboratory for buprenorphine testing. For ELISA analysis, samples were
      diluted 1:10 with K(2)HPO(4) (0.1M, pH 7.0). The limit of detection was
      calculated as 0.5 ng/mL buprenorphine. The intra-assay and interday precision was
      3.8% (n = 10) and 8.6% (n = 50) respectively at 1 ng/mL buprenorphine. At a low
      concentration of norbuprenorphine (1 ng/mL), the immunoassay demonstrated a cross
      reactivity of 78%. A higher cross-reactivity of 116% was observed at a higher
      concentration of norbuprenorphine (10 ng/mL). Dihydrocodeine, codeine, tramadol,
      morphine, propoxyphene, methadone, and EDDP were tested at concentrations of 10
      ng/mL and 10,000 ng/mL and demonstrated no cross-reactivity with the assay. For
      liquid chromatography-tandem mass spectrometry (LC-MS-MS), deuterated internal
      standard mixture, 1M acetate buffer (pH 5.0), and b-glucuronidase were added to
      the standards and samples, which were then incubated for 3 h at 60 degrees C.
      After incubation, 3 mL K(2)HPO(4) (0.1M, pH 6.0) was added and the pH altered to
      pH 6.0 using 1M KOH. Buprenorphine and norbuprenorphine were subsequently
      extracted by solid-phase. Twenty-one samples were confirmed positive and 48
      samples were confirmed negative by LC-MS-MS. Using a cut-off value of 0.5 ng/mL
      buprenorphine, the immunoassay demonstrated a sensitivity and specificity of
      100%.

PMID- 16620544
TI  - Anesthesiologist suicide with atracurium.
AB  - Atracurium is a nondepolarizing skeletal muscle relaxant used to facilitate
      endotracheal intubation and to induce skeletal muscle relaxation during surgery
      or mechanical ventilation. The drug undergoes a spontaneous non-enzymatic
      biotransformation, yielding laudanosine and an acrylate moiety. This report
      documents the case of a 45-year-old anesthesiologist who was found dead at the
      hospital where he worked. The victim was known to be depressed and undergoing
      treatment with venlafaxine. An empty syringe was found near the body.
      Toxicological analysis revealed the presence of laudanosine in the syringe, 0.6
      mg/L of laudanosine in heart blood, 0.3 mg/L in urine, and 0.02 mg/L in vitreous
      humor. Meanwhile, concentrations of venlafaxine and O-desmethyl-venlafaxine, its
      active metabolite, were 0.7 and 1.1 mg/L in heart blood, 1.7 and 5.2 mg/L in
      urine, 0.5 and 0.7 mg/L in vitreous humor, and 400 and 20 mg in gastric content,
      respectively. All drugs and metabolites involved in the case were detected using
      gas chromatography with nitrogen-phosphorus detection (GC-NPD) and confirmed
      using GC-mass spectrometry in full scan mode after solid-phase extraction using
      Bond-Elut Certify columns. Additional high-performance liquid chromatography
      coupled to diode-array detection screening also obtained the same results.
      Quantitation of laudanosine and venlafaxine together with its metabolite was
      carried out using GC-NPD. No other drugs, including ethanol, were detected.
      Recoveries for laudanosine and venlafaxine were 89% and 86%, respectively, at 0.5
      mg/L; intraday and interday precisions were 2% and 6%, and 3% and 7%,
      respectively; and limits of detection and quantitation were 6 and 20 ng/mL and 18
      and 59 ng/mL, respectively. The linearity of the blood calibration curves was
      excellent for both drugs with r(2) values of > 0.999 (range 0.1-2.0 mg/L). Based
      on the autopsy findings, case history, and toxicology results, the forensic
      pathologists ruled that the cause of death was an overdose of atracurium, and the
      manner of death was suicide.

PMID- 16620545
TI  - [The effects of different transcripts of AML1 on the transactivation of M-CSF-R
      gene].
AB  - OBJECTIVE: To observe the effects of AML1A and AML1B, two splicing isoforms of
      AML1, on the transactivation of macrophage colony-stimulating factor receptor (M
      CSF-R), and explore the mechanism of hematopoietic stem cell committed
      differentiation and leukemogenesis. METHODS: The expressive plasmids of AML1A and
      AML1B were constructed, and co-transfected into CV-1 cells with a luciferase
      reporter plasmid containing M-CSF-R promoter. The transactivity of M-CSF-R
      promoter was assayed by luminometer. RESULTS: AML1B exhibited a distinct
      transactivity to M-CSF-R promoter with a sequence-specificity and dosage
      dependent manner. AML1A showed no any transactivity but antagonized the effect of
      AML1B, causing marked reduction of M-CSF-R expression. CONCLUSION: An intact
      structure of AML1 is necessary for transactivation of M-CSF-R. AML1A may
      interfere with the transactivation of AML1B, and play a key role in the fine
      regulation of committed differentiation of hematopoietic cell.

PMID- 16620547
TI  - [Comparison of the effectiveness of chemotherapy and autologous hematopoietic
      stem cell transplantation as postremission treatment for adult acute
      lymphoblastic leukemia patients].
AB  - OBJECTIVE: To evaluate the effectiveness of chemotherapy (CT) and autologous
      hematopoietic stem cell transplantation (ASCT) as post-remission treatment for
      adult acute lymphoblastic leukemia (AL) patients. METHODS: Seventy-four ALL
      patients achieved first complete remission (CR(1)) with induction therapy, and
      then received early-stage sequential intensive consolidation chemotherapy. After
      that, 40 patients received chemotherapy (CT group) and 34 received ASCT (ASCT
      group) as post-remission treatment. The median follow-up was 20.5 months. The
      rates of leukemia free survival (LFS), overall survival (OS) and relapse were
      compared between the two groups. RESULTS: (1) The median LFS and OS were 14.0 and
      20.6 months respectively for CT group and both were more than 53.5 months for
      ASCT groups. (2) Relapse occurred in 28 patients (70%) in CT group in a median
      time of 8.5 months (range, 1-72 months) and 20 of them (71.43%) relapsed within 1
      year. Eleven patients (32.35%) relapsed in ASCT group, in a median time of 6 (2
      30) months after transplantation. (3) There was no statistic difference in LFS,
      OS and relapse rate at 1 year between CT and ASCT groups (P > 0.05), whereas both
      LFS and OS at 3 and 5 years for ASCT group were significantly better than those
      for CT group (P < 0.05). Relapse rate for ASCT group was lower than that for CT
      group. (4) Higher LFS and OS and lower relapse rate were found for those who
      received monoclonal antibody purged autografts followed by immunotherapy and (or)
      maintenance therapy after ASCT (P < 0.05). CONCLUSIONS: Early sequential
      intensive consolidation chemotherapy followed by auto-HSCT could significantly
      reduce late relapse rate for adult ALL patients, and those received ex vivo
      purged autografts and immunotherapy and (or) maintenance therapy after ASCT have
      lower late relapse rate and superior survival.

PMID- 16620548
TI  - [Significance of quantification of WT1 mRNA for monitoring minimal residual
      disease in acute myeloid leukemia patients].
AB  - OBJECTIVE: To evaluate the significance of quantification of WT1 mRNA for
      monitoring minimal residual disease (MRD) in patients with acute myeloid leukemia
      (AML). METHODS: WT1 mRNA level was detected with real-time quantitative RT-PCR
      (RQ-PCR) technique in bone marrow samples from 15 normal subjects (NBM) and 123
      AML patients. Sixty-two AML samples were also detected AML1-ETO mRNA expression
      by RQ-PCR. Simultaneously follow-up of WT1 and AML1-ETO levels were carried out
      in 50 samples from 8 AML patients. WT1 and AML1-ETO levels were normalized by
      internal control ABL gene. RESULTS: All correlation co-efficiencies were over
      0.99 for WT1, AML1-ETO and ABL standard curves. Co-efficiencies of both
      interassay and intraassay variation were below 4%. The WT1 expression levels in
      NBM were 0.001 to 0.019 with a median level of 0.008. Higher levels of WT1
      expression were found in 61 of 67 (91%) newly diagnosed AML patients compared
      with NBMs and 37 of the 67 (55.2%) showed 100-fold higher WT1 levels than that in
      NBMs. WT1 mRNA levels were highest in M(4EO) and M(3) and lowest in M(1) and M(5)
      patients. There was an excellent correlation between WT1 and AML1-ETO gene
      expression levels (r = 0.88, P < 0.001). WT1 expression levels in three patients
      who were in continuous complete hematological remission (CHR) were within normal
      range. In three of four relapsing patients, WT1 expression levels increased 31.4,
      11.4 and 4.0 fold respectively one month before hematological relapse.
      CONCLUSIONS: Quantification of WT1 expression level by RQ-PCR may be used to
      monitor MRD for most AML patients, but it is less sensitive than fusion gene.
      Continuous or significant increase of WT1 expression in CHR patients predicts an
      impending relapse.

PMID- 16620549
TI  - [Evolution of gene expression profile in 3 cases of acute myeloid leukemia].
AB  - OBJECTIVE: To investigate the mechanism of refractoriness of acute myeloid
      leukemia (AML) by studying the changes of gene mRNA expression from primary
      diagnosis to relapsed disease in AML. METHODS: Differences in gene expression
      profile of bone marrow mononuclear cells were compared between primary diagnosis
      and relapsed/refractory disease in 3 patients with M(2a) subtype of AML using
      Agilent human 1B 60mer oligonucleotide microarray. RESULTS: Common alterations
      were found in 10 genes among the 20173 genes tested at relapsed/refractory
      disease as compared with that at primary diagnosis in 3 patients. Of these 10
      genes, 7 were up-regulated while 3 down-regulated at relapse in all the 3
      patients. CONCLUSION: Development of relapsed/refractory disease in AML-M(2a)
      might be associated with the mRNA expression changes in the 10 genes tested
      including DAPK1. The alteration of these genes may be indications for the early
      diagnosis of refractoriness of AML, and these genes might provide new therapeutic
      targets for the treatment of refractory AML.

PMID- 16620550
TI  - [Analysis of 66 cases received hematopoietic stem cell transplantation from
      unrelated donors].
AB  - OBJECTIVE: To improve the outcome of hematopoietic stem cell transplantation from
      unrelated donors. METHODS: Sixty-six patients with hematological diseases (40
      cases of acute leukemia, 24 chronic myeloid leukemia, and one each severe
      aplastic anemia and beta-thalassemia) received bone marrow (BMT, n = 48) or
      peripheral blood stem cell transplantation (PBSCT, n = 18) from HLA-compatible
      unrelated donors after BUCY or TBI conditioning. Forty patients received longer
      and intensive GVHD prophylaxis (cyclosporin A from day -10 combined with
      mycophenolate mofetil). RESULTS: Sixty-four patients achieved sustained donor
      engraftment. The median time of leukocyte engraftment was 15 days, being
      significantly earlier in PBSCT group compared with BMT group (12 vs 16 days, P =
      0.002). The cumulative incidence rates of grades I-II and III-IV acute GVHD at
      day 100 were 57.15% and 32.25%, respectively. Chronic GVHD was seen in 21 of the
      36 evaluable cases and ten of them were extensive type. Six patients relapsed and
      27 dead, the overall survival at 5 years was 52.91%. The COX method analysis
      showed that HLA-compatible level and source of graft affected the incidence of
      aGVHD. The patients transplanted from HLA-matched donor with high resolution and
      PBSCT had the less probability for aGVHD. Patients without GVHD or with longer
      and intensive GVHD prophylaxis had significantly improved OS. CONCLUSION: The key
      to improvement the outcome of HCT from unrelated donor is to reduce the incidence
      and severity of aGVHD by selecting the HLA-matched donor, intensifying the
      immunosuppression at the early stage of transplantation.

PMID- 16620552
TI  - [A heterozygous point mutation G13328A in antithrombin gene causes thrombosis].
AB  - OBJECTIVE: To identify the phenotype and the gene mutation in a kindred with
      antithrombin (AT) deficiency. METHODS: Immuno-nephelometry and chromogenic assay
      were used to detect the plasma level of AT antigen (AT: Ag) and activity (AT: A),
      respectively. All the seven exons and intron-exon boundaries of AT gene from the
      propositus were amplified by PCR and direct sequencing of the PCR pro-ducts was
      performed. Corresponding PCR fragments from the kindred were also sequenced
      directly. Megaprimer method was used to construct the mutant AT cDNA expressing
      vector from normal plasmid pCRII AT cDNA. The normal and mutant AT plasmid were
      transiently transfected into Cos-7 cells and AT: Ag was detected in supernatant
      and lysate of transfected cell with ELISA. RESULTS: The plasma level of AT: Ag
      and AT: A for the propositus were 179 mg/L and 42.3%, respectively. A
      heterozygous G13328A missense mutation in exon 6 was identified, which led to the
      substitution of Thr (ACC) 404 for Ala (GCC). The sequencing results from the
      pedigree suggested that three other members also had the mutation. The level of
      AT:Ag in supernatant and lysate from cells transfected with mutant AT cDNA was
      40% and 68% of that of normal AT cDNA transfected cells. CONCLUSION: This is an
      unreported AT gene mutation in China, which causes type I hereditary antithrombin
      deficiency and thrombosis in the proposita.

PMID- 16620553
TI  - [Heme oxygenase-1 inhibits thrombosis under oxidative stress].
AB  - OBJECTIVE: To study the potential function and mechanism of heme oxygenase-1 (HO
      1) in regulating platelet reactivity and arterial thrombosis. METHODS: HO-1
      deficient (HO-1(-/-)) mice were generated by gene knock-out technique, and the
      genotyping of the mice was performed by PCR analysis of tail DNA. Thrombus
      formation was induced by applying FeCl(3) to the exposed carotid artery, and the
      occlusion time was monitored for each animal. Western blot and chemical assays
      were used to detect HO-1 and cGMP levels in platelets. Platelet aggregation
      induced by ADP was also studied. RESULTS: The difference between mean occlusion
      time of wild-type mice [(15.56 +/- 1.25) min, n = 16] and HO-1(-/-) mice [(12.85
      +/- 0.55) min, n = 14] was not statistically significant. However, after
      challenge with hemin, which induces HO-1 expression, mean occlusion time was
      significantly longer in wild-type mice [(16.25 +/- 1.20) min, n = 15] than in HO
      1(-/-) mice [(11.96 +/- 0.98) min, n = 19; P < 0.05]. Hemin administration which
      induced oxidative stress could markedly elevate HO-1 level and cGMP concentration
      in platelet, while suppress ADP induced platelet aggregation in wild type mice.
      CONCLUSION: Under conditions that stimulate HO-1 production, platelet-dependent
      thrombus formation is inhibited by HO-1 through the pathway of cGMP expression.
      It suggests that enhanced platelet HO-1 expression in response to physiological
      stress may represent an adaptive response mechanism to down-regulate platelet
      activation under pro-thrombotic conditions.

PMID- 16620554
TI  - [Study on the mechanisms of imatinib-resistance of cancer stem-like cells in
      K562/Vp16 cell line].
AB  - OBJECTIVE: To elucidate the mechanisms of imatinib resistance involved in some
      chronic myeloid leukemia (CML) cells overexpressing P-glycoprotein (P-gp).
      METHODS: Generation of resistant K562 cell line K562/Vp16 overexpressing P-gp was
      achieved by exposure of K562 cells to stepwise increase of concentrations of
      Vp16. A small set of side population (SP) with the characteristics of stem cells
      being capable of efflux fluorescent dye Hoechst 33342 in the cell line was
      isolated by flow cytometry. The mechanisms involved in K562/Vp16 SP cells
      resistant to imatinib were studied. RESULTS: The levels of BCR/ABL and ABL
      proteins in K562 cells were similar to those in K562/Vp16 non-SP and K562/Vp16 SP
      cells. The 170 KDa P-gp was detected in K562/Vp16 and K562/Vp16 SP cells at
      similar levels but not in K562 cells. Compared with K562/Vp16 non-SP cells,
      K562/Vp16 SP cells were more resistant to imatinib, which could hardly be
      reversed by many multidrug resistance inhibitors. In addition, in vivo study
      showed that the malignancy of K562/Vp16 cells was largely attributed to the SP
      cells. CONCLUSIONS: Bcr/Abl gene amplification and multidrug-resistant gene 1
      (mdr1) overexpression might not be an important clinical mechanism in the
      diversity of resistance to imatinib treatment, and the development of drug
      resistance by leukemia cells may be at least partly due to a rare SP of tumor
      stem-like cells which drives leukemia occurrence and maintenance. These SP cells
      might be targeted for effective cancer therapy.

PMID- 16620556
TI  - [Investigation of GSTT1, GSTM1 and NQO1 genes polymorphisms in myelodysplastic
      syndromes].
AB  - OBJECTIVE: To investigate the relationship between GSTM1, GSTT1 and NQO1(C609T)
      genotypes and myelodysplastic syndromes (MDS) susceptibility and chromosome
      abnormalities. METHODS: GSTT1, GSTM1 and NQO1(C609T) genotypes were detected in
      52 MDS patients and 241 unrelated controls by PCR or PCR-RFLP. RESULTS: The
      incidence of GSTT1 and GSTM1 null genotype was significantly increased in MDS
      patients as compared with controls (P = 0.001 and P < 0.001, respectively). In
      individuals with GSTT1 and GSTM1 null genotype, the odds ratios for MDS risk were
      elevated to 2.873 (95% CI: 1.491-5.537) and 3.591 (95% CI: 1.717-7.508),
      respectively. A significantly increased frequency of GSTT(1) null genotype among
      MDS patients with normal karyotype and increased frequency of GSTM1 null genotype
      among MDS patients with chromosome abnormalities were found as compared to
      controls (OR = 5.336, P = 0.005 and P = 0.003, OR = 3.740, respectively). There
      was no difference in the incidence of NQO1(C609T) genotypes between MDS patients
      and controls. CONCLUSION: Determination of the GSTM1 and GSTT1 genotypes may be
      used as a stratification marker to predicate high-risk individuals for MDS.

PMID- 16620557
TI  - [In vitro killing effect of mutant thymidine kinase mediated by lentiviral vector
      on T lymphocytes].
AB  - OBJECTIVE: To explore the killing effect of the mutant herpes simplex virus
      thymidine kinase (HSV-sr39tk) and its wild-type (HSV-tk) mediated by lentiviral
      vector on T lymphocytes in vitro and compare T cell survival rate after GCV or
      ACV treatment. METHODS: The three-plasmid lentiviral vector system including
      packaging plasmid DeltaNRF, envelope plasmid VSV-G and vector plasmid (pTK151 +
      HSV-sr39tk or pTK151 + HSV-tk) were cotransfected into human embryonic kidney
      293T cells using modified calcium phosphate precipitation methods. The packaged
      virus was harvested 72 h later. The survival of T cells expressing HSV-sr39tk or
      HSV-tk was measured by MTT assay after 4 day-culture against a gradient of GCV or
      ACV concentrations. RESULTS: The three plasmids were effectively cotransfected
      and a high titre of lentivirus was obtained (2 x 10(6) IU/ml). 39tk(+) T cell
      survival rates declined promptly when the prodrug GCV/ACV concentrations
      increased from 0 micromol/L to 10 micromol/L. The T cell survival rates in GCV
      group declined from (96.04 +/- 3.23)% to (36.76 +/- 4.38)% while in ACV group
      from (97.31 +/- 4.61)% to (43.75 +/- 8.99)%. However, when GCV/ACV concentrations
      were more than 10 micromol/L, further decline of 39tk(+) T cell survival rates
      became unobvious. The growth rate of 39tk(+) T cell exposed to GCV or ACV was
      obviously lower than that in un-transfected T cells (P < 0.05). Tk(+) T cells
      were sensitive to GCV (P < 0.05), but not to ACV (P > 0.05). There was a
      significant difference in killing effects between 39tk(+) T cell + GCV group and
      tk(+) T cell + GCV group (P < 0.05). CONCLUSION: The lentiviral vectors
      containing HSV-sr39tk gene could infect T lymphocytes effectively and stably
      without affecting the proliferation of the transduced cell. In contrast to HSV-tk
      gene, T cells infected HSV-sr39tk were more sensitive not only to GCV but also to
      ACV.

PMID- 16620570
TI  - [Effectiveness analysis of HA based triple-drug regimen as induction chemotherapy
      in the treatment of acute myeloid leukemia and its relationship with karyotype].
AB  - OBJECTIVE: To analyze the complete remission (CR) rate, disease free survival
      (DFS) and overall survival (OS) of de novo acute myeloid leukemia (AML) patients
      treated with HA based three drugs induction chemotherapy and to explore the
      impact of cytogenetic abnormalities on the prognosis. METHODS: Two hundred and
      forty-three untreated de novo AML patients were treated with HA based three drugs
      induction therapy. CR rate, DFS and OS were calculated. One hundred and eighty
      four patients who had karyotype results were divided into four or three groups
      according to SWOG or MRC criteria respectively. Differences in CR rate, DFS and
      OS among different groups were evaluated. RESULTS: The CR rate of all the 243
      cases was 77.4%. The median DFS of the 188 CR patients was 28.5 (ranged from 1.0
      to 153.0) months, DFS rates at 3 and 5 years were 45.4% and 40.2% respectively.
      The median OS of the 243 patients was 18.4 (range from 0.5 to 154.0) months. OS
      rates at 3 and 5 years were 36.9% and 31.4% respectively. According to SWOG
      criteria, CR rate, median DFS and OS were 97.8%, 87.4 months and 89.0 months for
      the favorable group; 81.9%, 17.6 months and 22.3 months for the intermediate
      group; 61.5%, 9 months and 11.5 months for the adverse group; and 79.3%, 29.0
      months, 19.9 months for the unknown group, respectively. The differences among
      the four groups were statistically significant (P < 0.001). According to MRC
      criteria, CR rate, median DFS and OS were 96.1%, 79.9 months, 72.2 months for the
      favorable group; 80%, 17.6 months, 19.7 months for the intermediate group; and
      43.8%, 16.5 months, 12 months for the adverse group, respectively. The
      differences among the three groups were statistically significant excepting for
      DFS between intermediate and adverse groups. CONCLUSIONS: HA based triple-drug
      induction regimens are highly effective in obtaining higher CR rate and longer
      survival time. Cytogenetics is the important prognostic factor for AML patients
      and SWOG karyotype subtyping criteria is more appropriate than that of MRC, the
      differences among the three groups being statistically significant.

PMID- 16620571
TI  - [Inhibition of vascular endothelial growth factor gene expression and
      proliferation of leukemia cells by RNA interference].
AB  - OBJECTIVE: To explore the feasibility of selective inhibiting VEGF expression
      using VEGF short hairpin RNA (shRNA) interference, and observe the effects of
      VEGF gene silencing on NB4 cells growth. METHODS: Three 19 bp reverse repeated
      motifs targeting exons 3, 4, 5 respectively of VEGF gene were synthesized and
      cloned into eukaryotic expression plasmid pGenesil-1 containing U6 shRNA promoter
      and termination signal of RNA polymerase. The recombinant plasmids pGenesil-VR1,
      pGenesil-VR2, pGenesil-VR3 and pGenesil-con (plasmid containing random DNA
      fragment) were transfected into NB4 cells respectively through lipofectamine
      reagent. The alteration of VEGF expression was examined by fluorescent real time
      RT-PCR and Western blot. The proliferation capacity of leukemia cells was
      measured by trypan blue exclusion, MTT assay, colony formation assay and cell
      cycles analysis. RESULTS: Recombinant plasmids containing three shRNAs and random
      fragment were successfully constructed and transfected into NB4 cells
      respectively by liposome-mediated gene transfer method. shRNA in pGenesil-VR3
      cells knocked down the expression of VEGF mRNA and protein dramatically in a
      sequence-specific manner when compared with that of pGenesil-VR1, Genesil-VR2 and
      pGenesil-con. The NB4 cells transfected with pGenesil-VR3 (NB4-VR3) had a more
      significant decrease in proliferation ability than NB4 and that transfected with
      pGenesil-con (NB4-con). The colony forming efficiencies of NB4-VR3, NB4-con and
      NB4 cell were (13.3 +/- 3.8)%, (21.3 +/- 6.4)% and (24.5 +/- 5.2)%, respectively
      (P < 0.05). Higher G(1) and lower S proportion were found in cell cycle
      distribution in comparison with the control groups by FCM. CONCLUSIONS: The shRNA
      can efficiently suppress VEGF expression in NB4 cells. Selective VEGF gene
      silence can inhibit the malignant proliferation of leukemia cells.

PMID- 16620572
TI  - [Effects of PLK1 gene silence on apoptosis of K562 cells].
AB  - OBJECTIVE: To investigate the effects of PLK1 gene silence by short hairpin RNA
      (shRNA) on PLK1 expression and apoptosis in K562 cells, and explore the role of
      PLK1 in the pathogenesis of leukemia. METHODS: The shRNA fragment targeting at
      1416-1436 bp of PLK1 mRNA was synthesized and cloned into pEGFP-H1 vector, named
      as pEGFP-H1/PLK1. The empty control, pEGFP-H1 and pEGFP-H1/PLK1 were transfected
      into K562 cells respectively via electroporation. 24 h or 48 h after
      transfection, gene and protein expression of PLK1 in the cells were assayed by RT
      PCR and Western blot analysis respectively, cells viability by MTT assay, caspase
      3 activity by colorimetry, cell cycle and apoptosis by FACS. RESULTS: 24 and 48 h
      after transfection, PLK1 expression in K562 cells was 1.25 +/- 0.07 for control
      group, 0.52 +/- 0.04 and 0.25 +/- 0.02 for pEGFP-H1/PLK1 group, and 1.24 +/- 0.08
      and 1.23 +/- 0.09 for pEGFP-H1 group respectively. The alteration status of PLK1
      protein levels were similar to that of PLK mRNA levels. The apoptosis rate was
      (8.3 +/- 0.6)% in control group, (8.7 +/- 0.7)% in pEGFP-H1 group and (49.7 +/-
      3.8)% and (82.3 +/- 6.9)% in pEGFP-H1/PKLK1 group at 24 and 48 h, respectively.
      In addition, cell fraction at G(2)/M phase was increased obviously compared with
      control and pEGFP-H1-transfected group. CONCLUSION: The constructed shRNA can
      remarkably inhibit PLK1 expression and transfected K562 cell proliferation,
      increase apoptosis and block cell-cycle, suggesting that PLK1 play important
      roles in apoptosis and cell-cycle control of leukemia cells.

PMID- 16620573
TI  - [Reversal of multidrug resistance of K562/A02 cell line by mdr1 and GSTpi gene
      silence].
AB  - OBJECTIVE: To investigate the effect of short hairpin RNA (shRNA) on mdr1 and
      GSTpi expression of human multidrug resistant leukemia cell line K562/A02.
      METHODS: shRNAs were synthesized according to the sequence targeting mdr1 and
      GSTpi coding region of 79-99nt and 308 approximately 327nt, and cloned into
      pSilencer 2.1-U6 neo vector. The cloned products, pSilence-mdr1 and pSilence
      GSTpi, were transfected into K562/A02 cell line. Expression of mdr1 and GSTpi
      mRNA was assayed by real time PCR. 50% inhibition concentration (IC(50)) of
      doxorubicin (ADM) for K562/A02 cell line was determined by MTT method. RESULTS:
      After transfected with pSilence mdr1, the expression of mdr1 mRNA in K562/A02
      cells was reduced by 71.5%, from (2.80 +/- 1.65) x 10(8) copy/microg RNA to (3.90
      +/- 2.37) x 10(7) copy/microg RNA(P < 0.01). While the expression of GSTpi mRNA
      in pSilence-GSTpi transfected K562/A02 cells reduced by 39.8%, from (2.30 +/-
      1.14) x 10(5) copy/microg RNA to (5.40 +/- 2.45) x 10(4) copy/microg RNA (P <
      0.01). The resistance indexes after transfection were decreased to 8 and 10
      respectively as compared to 23 of the mock transfection (P < 0.01). CONCLUSION:
      The shRNA could effectively reverse the multidrug resistance of K562/A02 cell
      line.

PMID- 16620575
TI  - [Expression, localization and interrelationship of P27kip1 and cyclin D3 in non
      Hodgkin's lymphoma].
AB  - OBJECTIVE: To investigate the expression, localization and interrelationship of
      P27(kip1) and cyclin D3 in non-Hodgkin's lymphoma (NHL). METHODS: The expressions
      of P27(kip1), cyclin D3 and index Ki-67 was detected in 100 NHL and 20 reactive
      lymph nodes by immunohistochemical technique. The expression and localization of
      P27(kip1) and cyclin D3 in 3 NHL cell lines were detected by Western blot, double
      immunolabelling and laser scanning confocal microscopy, respectively. RESULTS: In
      general the expression of P27(kip1) in NHL was lower than in control group, and
      was negatively related to the tumor aggressiveness and proliferating activity;
      the expression of cyclin D3 in NHL was higher than in control group, and was
      positively related to the tumor aggressiveness and proliferating activity. There
      was a negative correlation between P27(kip1) and cyclin D3. Nevertheless,
      anomalous high P27(kip1) expression was found in a few NHL tissues with high
      expression of cyclin D3 and Ki-67. Overexpression and colocalization of P27(kip1)
      and cyclin D3 was found in Raji cell line. CONCLUSIONS: Under expression of
      P27(kip1) and overexpression of cyclin D3 may play a role in the occurrence and
      development of NHL. Anomalous high P27(kip1) expression and its interaction with
      cyclin D3 may be another mechanism for tumor genesis of NHL.

PMID- 16620576
TI  - [The heat shock protein 90 inhibitor induces apoptosis and differentiation of
      Kasumi-1 and its mechanisms].
AB  - OBJECTIVE: To explore the effect of 17-allylamide-17-demethoxygeldanamycin
      (17AAG), a heat shock protein 90 (HSP90) inhibitor, on the growth,
      differentiation and apoptosis of leukemic Kasumi-1 cells. METHODS: Kasumi-1 cells
      were treated with 17AAG at different concentrations in suspension culture. Cell
      proliferation was analysed by MTT assay, expression of myeloid-specific
      differentiation antigen and cell cycle by flow cytometry, cell apoptosis by
      annexin V staining, agarose gel electrophoresis and flow cytometry. KIT protein
      was analysed by Western blot and c-kit mRNA by RT-PCR. RESULTS: 17AAG treatment
      caused a dose-dependent inhibition of the cell proliferation with the IC(50) of
      0.62 micromol/L. A dose-dependent increase in early apoptosis occurred at 24
      hours treatment and in late apoptosis at 48 hours treatment. 17AAG induced a time
      and dose-dependent increase in expression of myeloid cell surface protein CD11b
      and CD15, a progressive decline in S-phase cell fraction and an increase in
      G(0)/G(1) cells. When Kasumi-1 cells were incubated with 1 micromol/L of 17AAG,
      KIT protein began to decrease at 2 hours and KIT protein could hardly be detected
      at 20 hours, but c-kit mRNA was not decreased. CONCLUSION: 17AAG treatment of
      Kasumi-1 cells could lower KIT protein expression, inhibit cell proliferation,
      induce cell partial differentiation, apoptosis and accumulation in G(0)/G(1)
      phase.

PMID- 16620577
TI  - [Mesenchymal stem cells from human cord blood promote engraftment of human
      umbilical cord blood-derived CD34+ cells in NOD/SCID mice].
AB  - OBJECTIVE: To explore whether the co-transplantation of mesenchymal stem cells
      (MSC) from human umbilical cord blood (UCB) with UCB-derived CD34(+) cells in
      NOD/SCID mice could promote engraftment and accelerate hematopoiesis recovery.
      METHODS: After sublethal irradiated ((60)Co 2.5 Gy), NOD/SCID mice received
      within 24 hours UCB CD34(+) cells (1 x 10(5) per mouse for low dosage group or 1
      x 10(6) per mouse for high dosage group) with or without human UCB-derived MSC (1
      x 10(6) per mouse) transplantation by lateral tail vein injection. Peripheral
      blood cells of transplanted mice were measured for white blood cell count,
      hemoglobin and platelet count at 10th, 20th, 30th, 40th and 56th day. At the end
      of 8th week after transplantation, all the alive mice were sacrificed and human
      derived CD45(+), CD45(+)CD3(+), CD45(+)CD19(+), CD45(+)CD33(+) cells in the bone
      marrow (BM) were assayed by flow cytometry. RESULTS: (1) In the low dosage group,
      co-transplantation of MSC significantly raised the engraftment rate (26.02% vs
      16.52%) (P < 0.05). (2) The survival rate in high dosage group was 80% for co
      transplantation mice and 70% for CD34(+) cells alone transplantation mice. The
      survival rate in low dosage group was 70% for co-transplantation mice and 50% in
      CD34(+) cells transplantation mice. (3) In both dosages groups co-transplantation
      accelerated the hematopoiesis recovery. (4) At the end of 8 weeks after
      transplantation, in low dosage group, CD45(+)CD33(+) and CD45(+)CD19(+) cells
      were more in co-transplantation mice than in CD34(+) cells alone transplantation
      mice, but in high dosage group, the percentage of these two kinds of cells had no
      difference. In both dosage groups the percentage of CD45(+)CD41a(+) cells were
      higher in co-transplantation than in transplantation alone mice. CD45(+)CD3(+)
      cells were low in all groups. CONCLUSIONS: (1) In low dosage transplantation,
      human UCB MSC could promote human CD34(+) cells engraftment in transplanted mice.
      (2) Co-transplantation of human UCB MSC and human UCB CD34(+) cells could
      significantly promote the hematopoiesis reconstitution and improve the survival
      rate of NOD/SCID mice. (3) MSC could promote human UCB CD34(+) cells to
      differentiated into B-lymphocytes, granulocyte and megakaryocyte in vivo.

PMID- 16620579
TI  - [Experimental study of T lymphocyte reactivity inhibited by allogeneic bone
      marrow mesenchymal stem cells].
AB  - OBJECTIVE: To address the question whether bone marrow mesenchymal stem cells
      (MSCs) could lower responsiveness of allogeneic T lymphocytes against
      alloantigens, and explore a feasible strategy for prevention of graft versus host
      disease (GVHD) occurred in allogeneic bone marrow transplantation. METHODS: T
      cells were co-cultured with (60)Co-irradiated bone marrow MSCs from different
      individuals. The proliferative activity of T cells and their reactivity to
      allogeneic cells and ConA were evaluated with (3)H-TdR incorporation assay.
      RESULTS: T cells could not be activated upon primary or even secondary exposure
      to allogeneic MSCs (compared the CPM value of 27,529 +/- 969 of T cell alone with
      that of primary and secondary exposures to allogeneic MSCs were 9,126 +/- 654 and
      13,260 +/- 874, respectively). When MSCs were induced to express HLA-DR, they
      still could not elicit T cell activation. The proliferation rate of allogenous T
      cells exposed to MSCs was dramatically declined when T cells from the same
      donor's MSCs were used as stimulator (CPM value decreased from 45,876 +/- 5285
      before coculture to 9850 +/- 1618 after coculture). Furthermore, the results
      remained unchanged even ConA was added into the culture system. CONCLUSIONS:
      Heterogenetic MSCs could suppress T cell activation. MSCs pretreatment might be
      useful in the prevention of GVHD in HLA-mismatched bone marrow transplantation.

PMID- 16620578
TI  - [The inhibition pathway of the EBV-immortalized cells in children with infectious
      mononucleosis].
AB  - OBJECTIVE: To explore the inhibition pathway of the EBV-immortalized cells
      (CD23(+)) in children with infectious mononucleosis (IM) caused by Epstein-Barr
      virus. METHODS: The expressions of CD23, CD19, CD95, Bcl-2 and the co-expressions
      of CD23CD95, CD19CD23 on peripheral blood mononuclear cell (PBMC) were analyzed
      by flow cytometry (FCM) during acute phase, early convalescent phase and
      convalescent phase of 34 EBV-IM children and compared with that of 24 healthy
      donors. RESULTS: (1) The levels of CD23(+) and CD23(+)CD19(+) cells decreased and
      CD95(+), CD95(+)CD23(+), Bcl-2(+) cells increased markedly in IM patients in
      acute phase [CD95(+) cells (19.43 +/- 8.46)%; CD95(+)CD23(+) cells (1.81 +/-
      1.71)%; Bcl-2(+) cells (23.41 +/- 26.47)%] and early convalescent phase [CD95(+)
      cells (12.94 +/- 5.05)%; CD95(+)CD23(+) (1.05 +/- 1.20)%; Bcl-2(+) cells (10.54
      +/- 9.68)%], as compared with those of healthy controls [CD95(+) cells (10.39 +/-
      2.90)%; CD95(+)CD23(+) cells (0.50 +/- 0.46)%; Bcl-2(+) cells (7.25 +/- 2.88)%].
      The earlier the course of IM, the more abnormal the expressive levels. All the
      abnormal results returned to normal in convalescent phase. (2) Positive
      relationships were observed between the expressions of CD95(+)CD23(+) cells and
      that of CD23(+) cells, CD23(+)CD19(+) cells during acute and early convalescent
      phase, the expressions of Bcl-2(+), CD3(+) cells and CD23(+), CD23(+)CD19(+)
      cells during acute phase, the expressions of CD95(+)CD23(+) cells and Bcl-2(+)
      cells during acute phase, and the expressions of CD95(+)CD23(+) cells and CD95(+)
      cells during convalescent phase. CONCLUSION: The results indicate that CD95L-CD95
      mediated apoptosis plays an important role in eliminating EBV-immortalized cells,
      which is counteracted partly by Bcl-2.

PMID- 16620580
TI  - [Study of Th cell subsets in bone marrow of myelodysplastic syndromes patients].
AB  - OBJECTIVE: To study the quantity and ratio of Th1, Th2 cells in the bone marrow
      of myelodysplastic syndromes (MDS) patients, and to evaluate the correlation
      between the ratio of the blast cells and the number of the Th1 cells in the bone
      marrow of MDS patients. METHODS: By FACS, the quantity and ratio of IFN-gamma
      producing CD4(+) T cell (Th1) and IL-4 producing CD4(+) T cell (Th2) cells in the
      bone marrow were detected in 21 MDS patients, 18 normal controls and 13 severe
      aplastic anemia (SAA) patients respectively. The karyotypes of 18 MDS patients
      and 15 normal controls were assayed. The correlation between the ratio of the
      blast cells in the bone marrow and the number of the Th1 cells in the MDS
      patients were analyzed. RESULTS: The percentages of Th1 cells, Th2 cells and
      ratio of Th1/Th2 in the bone marrow of normal controls were (0.48 +/- 0.10)%,
      (0.24 +/- 0.19)% and 2.31 +/- 0.76 respectively, while those of the MDS patients
      were (0.36 +/- 0.11)%, (0.76 +/- 0.35)% and 0.51 +/- 0.13. The percentage of Th1
      cells of patients with MDS was reduced and the Th1/Th2 ratio was significantly
      lower than that of normal controls (P < 0.01). Those of the patients with SAA
      were (4.75 +/- 0.49)%, (0.40 +/- 0.28)% and 26.5 +/- 8.79 respectively, their Th1
      cells and Th1/Th2 ratio were markedly higher than those of normal controls (P <
      0.01). In all of the 15 normal controls the karyotypes were normal, but that of
      MDS patients was (50.00 +/- 0.10)%. The lower ratio of the Th1 cells in the bone
      marrow of the patients with MDS and the AML which progressed from MDS was
      negatively correlated with the higher percentage of the blast cells (r = -0.563,
      P < 0.01). CONCLUSIONS: (1) The immune function of T lymphocytes in MDS is
      abnormal: the balance between Th1 and Th2 cells is broken. (2) With descending of
      the number of Th1 cells in the bone marrow of the MDS patients, the disease is
      progressing to leukemia.

PMID- 16620589
TI  - [China being expected to lead the development tread of world public health].

PMID- 16620590
TI  - [A five-year observation on efficacy of revaccination in children of non-response
      to hepatitis B vaccine].
AB  - OBJECTIVES: To evaluate the long-term efficacy of revaccination in non-responder
      children to primary hepatitis B (HB) vaccination and to compare the efficacy of
      low-dose intradermal inoculation to that of routine-dose intramuscular
      inoculation. METHODS: 40 healthy non-responder children to primary HB vaccination
      identified by screening were given a three-dose revaccination randomly by
      intramuscular (n = 17, 10 microg per dose) or intradermal route (n = 23, 2 microg
      per dose) since September, 1999, and their blood specimens were collected
      regularly for testing for HB virus markers up to five years. Another 80 responder
      children to primary HB vaccination were also followed-up as controls without
      revaccination. By the end of five-year follow-up, HBsAg-specific lymphocyte
      response was investigated in vitro, and a booster dose (5 microg) was given to
      those with negative conversion of anti-HBs and their anamnestic responses were
      evaluated 12-14 days later. RESULTS: Serum anti-HBs did not reach 10 IU/L only in
      one of 40 non-responder children, who received intradermal revaccination. In the
      fifth year after revaccination, 50% of the non-responder children who received
      intramuscular revaccination still maintained anti-HBs of > or = 10 IU/L, though
      the rate was significantly lower than 85% in controls. Following the booster
      dose, a robust anamnestic response was developed in all of 8 intramuscular
      revaccinees and 11 controls but 16 of 18 intradermal revaccinees, who lost anti
      HBs of > or = 10 IU/L over time, and geometric mean titers of anti-HBs climbed to
      208, 105, and 549 IU/L, respectively. Secretions of HBsAg-specific interleukin-2
      and -5 could be detected in peripheral blood mononuclear cell samples of more
      than 70% of non-responder children. Person-year infection rates of HB virus were
      8.9% (8/89.9 person-years) for intradermal revaccinees, significantly higher than
      3.6% (12/337.2 person-years) in controls, and 4.3% (3/70.2 person-years) for
      intramuscular revaccinees, approximating to that of controls, based on positive
      conversion of anti-HBc. CONCLUSIONS: Three-dose intramuscular revaccination did
      play an important immune protection for non-responder children to primary HB
      vaccination, but its efficacy could not reach the level of primary vaccination in
      responders. Low-dose intradermal inoculation was not as effective as route-dose
      intramuscular inoculation with the same doses in revaccination for non-responder
      children to primary HB vaccination.

PMID- 16620591
TI  - [Association between genetic polymorphisms of metabolic enzymes and
      susceptibility of colorectal cancer].
AB  - OBJECTIVE: To investigate the association between CYP1A1, GSTM1, T1, UGT1A7
      polymorphisms and colorectal cancer risk. METHODS: A case-control study of 140
      patients with cancers and 343 health controls was conducted to investigate the
      role of CYP1A1, GSTM1, T1, UGT1A7 polymorphisms in colorectal cancer. Gene-gene
      interactions among CYP1A1, GSTM1, T1, UGT1A7 polymorphisms were detected by case
      control study and case-only study. Genotypes of four genes polymorphisms were
      analyzed by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and unconditional logistic regression was adopted to analyze the data.
      RESULTS: The CC, TC and CC genotypes of CYP1A1 T6235C significantly decreased the
      colorectal cancer risk as compared to TT genotype (OR = 0.493, 95% CI: 0.254
      0.956, OR = 0.638, 95% CI: 0.427-0.952). GSTM1 and GSTT1 null genotype had no
      significant association with the increased risk of colorectal cancer while the
      mutant variants of UGT1A7 might increase the risk of colorectal cancer
      significantly (OR = 2.501, 95% CI: 1.456-4.296). The CORvalue for the gene-gene
      interactions between CYP1A1 variant and the null genotype of GSTT1, GSTM1-deleted
      and GSTT1-deleted genotype in the case-only design were 2.617 (95% CI: 1.015
      6.752) and 3.935 (95% CI: 1.323-11.706), respectively. There was no significant
      interaction between CYP1A1 and GSTM1, CYP1A1 and UGT1A7. CONCLUSION: This study
      suggests that CYP1A1 and UGT1A7 variants might be associated with colorectal
      cancer. CYP1A1 and GSTM1 might interact on GSTT1 to influence the risk of
      colorectal cancer.

PMID- 16620592
TI  - [Experimental study on effects of iodine deficiency and excess on thyroid
      autoimmunity].
AB  - OBJECTIVE: To observe the effects of iodine on the level of CD4/CD8 cells and the
      production of thyroglobulin autoantibody (TGAb) and thyroid peroxidase
      autoantibody (TPOAb) in Wistar rats and to investigate the role of iodine in
      thyroid autoimmunity. METHODS: Rat models with different iodine intakes including
      low iodine (LI,), normal iodine (NI,), 5 times normal iodine (5HI), 10 times
      normal iodine (10HI), 50 times normal iodine (50HI) and 100 times normal iodine
      (100HI) were established. The amount of iodine intake per rat per day in every
      group was about < 1, 6.15, 30.75, 61.50, 307.50, 615.00 microg separately. The
      levels of CD4 and CD8 immune cells in peripheral blood were measured by using
      flow cytometry. Radioimmunoassay (RIA) was used to determine the titers of TGAb
      and TPOAb in the serum. RESULTS: In peripheral blood, the level of CD4 cells in
      LI group was (57.9 +/- 4.3)%, being much higher than in NI group (51.2 +/- 4.9)%.
      When the level of CD8 cells in 100HI group was (18.4 +/- 3.1)% showing
      significantly lower than in NI group (26.5 +/- 4.1)%, thus making the ratio of
      CD4/CD8 cells in the above two groups (LI: 2.4 +/- 0.40 and 100 HI: 2.7 +/- 0.4)
      higher than in NI group (1.9 +/- 0.3). As comparing with NI group (2099 +/- 220)
      CPM, the level of TGAb in LI group (1510 +/- 221) CPM was significantly
      decreased; while in 50HI group (3986 +/- 286) and 100HI group (3550 +/- 378) CPM,
      the levels of TGAb were both increased, and the levels of TPOAb in 10HI group
      (2066 +/- 184) CPM and in 50HI group (2141 +/- 163) CPM were both distinctly
      lower than in NI group (2372 +/- 245) CPM. CONCLUSIONS: Iodine might exert
      influence on the level of CD4/CD8, and thus the production of thyroid antibodies
      might directly or indirectly take part in the process of thyroid autoimmunity.
      Both low iodine and 100 times normal iodine intakes might activate the immune
      state on some degrees. The effects of iodine on immune responses of TG and TPO
      antigen in thyroid autoimmunity might not be completely the same.

PMID- 16620593
TI  - [Effects of NMDA receptor expression in rat's hippocampus after exposure to 1800
      MHz radiofrequency field].
AB  - OBJECTIVE: To identify the effects of NMDA receptor subunits NR2A and NR2B
      expression in rat's hippocampus after exposure to 1800 MHz radiofrequency
      radiation. METHODS: Four-week old female Wistar rats were randomly divided into
      four groups, with 12 animals for each. The subjects in two experimental groups
      had been continuously exposed to 1800 MHz microwave radiation (CW) with
      respective power density of 0.5 mW/cm(2) and 1.0 mW/cm(2) 12 hours each day for
      21 days. Meanwhile, sham-controls were carried out. The brain tissue sections
      were performed by immunohistochemistry to demonstrate both expressions of NR2A,
      NR2B immune-activity in the hippocampal CA1, CA3 and DG by using computer
      assisted image analysis system. RESULTS: In NR2A: the expression of 0.5 mW/cm(2)
      power density group was significantly lower than 0 mW/cm(2) power density group
      in CA3 [(8.5 +/- 1.5) vs (11.1 +/- 1.8), P < 0.01] and had not been significantly
      changed in CA1 and DG. The expression of 1.0 mW/cm(2) power density group was
      significantly lower than 0 mW/cm(2) power density group in CA1 and CA3 [(7.9 +/-
      1.6) vs (9.7 +/- 1.5); (8.4 +/- 1.7) vs (11.1 +/- 1.8), respective P < 0.05, P <
      0.01] and had not been significantly changed in DG. In NR2B: the expression of
      0.5 mW/cm(2) power density group was significantly lower than 0 mW/cm(2) power
      density group in CA1 and CA3 [(16.4 +/- 1.0) vs (17.8 +/- 1.6); (9.6 +/- 1.9) vs
      (11.2 +/- 2.1), respective P < 0.05]. The expression of 1.0 mW/cm(2) power
      density group was significantly lower than 0 mW/cm(2) power density group in CA1,
      CA3 and DG [(13.1 +/- 2.4) vs (17.8 +/- 1.6); (9.3 +/- 1.4) vs (11.2 +/- 2.1);
      (7.3 +/- 0.1) vs (8.5 +/- 1.0), respective P < 0.01, P < 0.05, P < 0.05].
      CONCLUSION: There were findings of the effects on NMDA receptor subunits in
      different hippocampus sections after exposure to 1800 MHz radiofrequency
      radiation.

PMID- 16620594
TI  - [Comparison on resistance of bacteriophages to sodium dichloroisocyanurate in
      laboratory].
AB  - OBJECTIVE: To scan the most resistable bacteriophage as an indicator in
      disinfection tests, and to study the resistance of bacteriophage T4, Phichi 174D,
      and f2 to the sodium dichloroisocyanurate (NaDCC) in laboratory. METHODS: The
      virucidal activity of NaDCC against bacteriophage T4, Phichi 174D, and f2 were
      assessed by suspension test. The neutralizer was selected and be appraised by
      test of neutralizer. Bacteriophage T4, Phichi 174D, and f2 were detected and
      enumerated by the double-agar-layer plaque technique. RESULTS: (1) With 150 mg/L
      of available chlorine of NaDCC solution, within a contact time of 40 minutes, or
      300 mg/L, 5 minutes, the reductions of bacteriophage T4 achieved the
      "disinfection" level [log(10) inactivation value or log(10) reduction value of
      bacteriophage T4 (log(10)No-log(10)Nt) > or = 4.00 log(10)]. (2) With 300 mg/L of
      available chlorine of NaDCC solution, within a contact time of 5 minutes, or 400
      mg/L, 3 minutes, the reductions of bacteriophage Phichi 174D achieved the
      "disinfection" level. (3) With 2000 mg/L of available chlorine of NaDCC solution,
      within a contact time of 20 minutes, or 4000 mg/L, 5 minutes, the reductions of
      bacteriophage f2 might achieve the "disinfection" level. CONCLUSION: The order of
      resistance of the above three bacteriophages to NaDCC from greatest to smallest
      is as follows: bacteriophage f2 > bacteriophage T4 > bacteriophage Phichi 174D.

PMID- 16620596
TI  - [Secular trend of nosocomial pneumonia in an university hospital in Zhengzhou].
AB  - OBJECTIVE: To investigate the secular trend of infection rate, risk factor
      exposure rates for nosocomial pneumonia (NP), and to evaluate the nosocomial
      infection surveillance and control programs efficacy in an university hospital
      from 1993 to 2000. METHODS: All 126 665 hospitalized patients from 1993 to 2000
      were studied for NP. The independent risk factors for NP were analyzed by using
      case-control study method and logistic regression technique. The time-specific
      rates for NP and risk factor exposure were calculated annually. RESULTS: The
      infection rates for NP were decreased by 50% from 1.20% in 1993 to 0.60% in 2000.
      The logistic regression analysis showed that the independent risk factors for NP
      were immunosuppressive therapy (OR = 2.72), chemotherapy (OR = 2.17), cancer (OR
      = 1.45), chronic obstructive pulmonary disease (COPD, OR = 1.88), ICU (OR =
      3.18), coma (OR = 3.26), tracheotomy (OR = 14.95), hemodialysis (OR = 5.12), bone
      or lumbar puncture (OR = 1.82). The time-trends for exposure rates of COPD and
      bone or lumbar puncture were slightly decreased, however those for the others and
      the synthetic risk factors were not changed significantly. CONCLUSION: The
      infection rates for NP were significantly decreased in the case of no change for
      exposure rates of risk factors for NP, this suggests that the nosocomial
      infection surveillance and control programs were effective for lowering infection
      rate for NP in this hospital.

PMID- 16620597
TI  - [Surveillance on contamination of total aflatoxins in corn, peanut, rice, walnut
      and pine nut in several areas in China].
AB  - OBJECTIVE: To realize the contamination of total aflatoxins in corn, peanut,
      rice, walnut and pine nut in China, and provide the base data for establishing a
      China tolerance limit standard and an international control practice for total
      aflatoxins. METHODS: The samples of corn, peanut, rice, walnut and pine nut from
      Chongqing, Fujian, Guangdong, Guangxi, Hubei, Jiangsu, Shanghai and Zhejiang
      provinces and municipalities were collected randomly from markets, with the
      totally 284 samples. The samples were grounded and added to acetonitrile/water
      mixture. After filtering, the extract was transferred into a purifying column and
      pressed slowly. Then the purified liquid was derivatized with trifluoroacetic
      acid (TFA) and detected by using a high performance liquid chromatography (HPLC).
      RESULTS: There was 70.27% corn having been detected out an average level of
      aflatoxins of 36.51 microg/kg and the highest level was 1098.36 microg/kg. At the
      same time, there was 14.86% corn exceeding the China national tolerance limit. In
      peanut, the aflatoxins detected rate was 24.24%. The average level was 80.27
      microg/kg and the highest level was 437.09 microg/kg. While there was 3.03%
      peanut exceeding the China national and Codex tolerance limits. All of the rice,
      walnut and pine nut samples met the China tolerance limit for aflatoxins.
      CONCLUSION: Corn and peanut might be the severely contaminated foods with
      aflatoxins in China. The aflatoxin B(1) in foods might be can not delegate the
      contamination of aflatoxins completely. Surveillance of total aflatoxins in foods
      suggested an actual need of establishing the China national and international
      standards for total aflatoxins.

PMID- 16620599
TI  - [Gene expression profiles on three kinds of genotype hepatitis C virus core
      protein in Huh-7 cell line with microarray analysis].
AB  - OBJECTIVE: To analyze three kinds of genotype hepatitis C virus (HCV) core
      protein expressed in human hepatoma (Huh-7) cell line and to recognize HCV core
      proteins biological function and its pathogenic mechanism. METHODS: The Huh-7
      cell expressed three kinds of core proteins were established respectively.
      Affymetrix human gene chip was used for identifying the gene expression
      dependently on Affymetrix's protocol. All genes changed by 3 or 1.5 folds between
      the transfected cells and a control cells were further analyzed, and annotated by
      using NetAffx analysis through Affymetrix website and were categorized based on
      their biological processes. RESULTS: The HCV-1b core protein caused 16 genes
      up/down-regulated expression, of which the immune response genes of PF4V1 and
      SPP1 were up-regulated 3.4 or 4.4 folds respectively. The HCV-2a core protein had
      caused the immune response gene CXCL5 and apoptosis gene BTF a down-regulated
      expression of 3.4 and 3.1 folds respectively, but caused the apoptosis genes of
      HRK and LZTS1 an up-regulated expression of 3.2 and 3.4 folds respectively. As
      compared with HCV 1b or 2a core protein, HCV-4b core protein caused 111 genes
      expression changing and it had more obvious effects on gene expression. If we
      applied 1.5 fold change for a comparison gene expression, a few of the same gene
      expression profiles might be caused by these two core proteins. CONCLUSION: The
      three kinds of HCV core protein should have its own expression character and be
      mainly shown in immune responses, signal transduction, apoptosis, etc. It should
      be helpful for our recognizing the HCV core protein biological function and its
      pathogenic mechanism.

PMID- 16620600
TI  - [Status and influencing factors of mercury exposure in neonates and their mothers
      in Zhoushan].
AB  - OBJECTIVE: To investigate the status of mercury exposure of neonates and their
      mothers in Zhoushan City, and analyze the related influencing factors. METHODS:
      From Aug to Sep, 2004, 408 neonate-mother pairs were cluster sampled at the Third
      People's Hospital in Dinghai region, Zhoushan City, and a further investigation
      for the neurobehavioral development of these children was followed up in a year.
      The contains of mercury of 14 kinds of fish, 5 pieces of each kind bought in
      markets of Dinghai region were detected. RESULTS: The geometric mean of cord
      blood Hg was 27.81 nmol/L (5.58 microg/L), while that of hair Hg of mothers was
      1246.56 microg/kg. 69.9% of pregnant women had surpassed the RfD (reference dose,
      0.1 microg/kg/day) for Hg intake. There was a strong correlation between hair and
      cord blood Hg levels (r = 0.821). The factors influencing cord-blood Hg levels
      were fish dinners, dwelling time, and fathers smoking or not, while those of hair
      Hg were fish dinners and dwelling time. The correlation between fish dinners and
      the cord blood Hg as well as hair Hg were of significance (r = 0.539, 0.481
      respectively), the Hg levels were higher in more fish dinners (H = 119.805,
      94.384 respectively). The mean fish Hg level at Dinghai region was low (< 0.1
      mg/kg), and no samples were higher than 0.5 mg/L. Two samples of cutlassfish and
      dried eel contained higher Hg than the others, belonging to a middle level (0.1
      0.5 mg/kg). CONCLUSIONS: Hg levels in neonates and pregnant women were generally
      below those considered hazardous, but the safety margin was narrow for some women
      and supporting efforts should be made to reduce mercury exposure. The main
      resource of Hg was from eating fish, and it is necessary to investigate the Hg
      levels in large samples, as to developing the fish advisories for susceptible
      people.

PMID- 16620602
TI  - [Investigation of nutrition and feeding status among children under 2 years in
      Beijing].
AB  - OBJECTIVE: To investigate the nutrition status, breast feeding and complementary
      feeding among children under 2 years of age in Beijing. METHODS: A stratified
      cluster randomly sampling method was used. After having got the compliance a
      questionnaire survey was carried out to 422 children < 2 year-old in total 18
      districts of Beijing. RESULTS: The average infant birth weight was 3325 g, the
      rate of weight (2500 g and > or = 4000 g were 2.8% and 13.0% respectively. The
      rate of exclusive breast-feeding, partial breast-feeding, bottle-feeding of
      infant under 4 months was 56.6%, 33.9% and 9.5% respectively. The average weaning
      time was 7.4 months. The rate of complementary feeding of infant up to 6 months
      was 99.4%. The average ages for addition of complementary feeding such as cereal,
      vegetable and fruit, egg, oil, nutrients in rural areas were later than those in
      urban. CONCLUSION: It is important to promote breast feeding and improve
      complementary feeding by education and intervention.

PMID- 16620604
TI  - [The relationship between test anxiety and personality, self-esteem in grade one
      senior high students].
AB  - OBJECTIVE: To explore the relationship between test anxiety and personality, self
      esteem in grade one senior high school students. METHODS: Totally 538 senior high
      school students of grade one were investigated by Test Anxiety Scale (TAS),
      Eysenck Personality Questionnaire (EPQ) and Self-Esteem Scale (SES) in a Senior
      High School in Shandong Province. RESULTS: The prevalence of test anxiety among
      all the surveyed students was rated 65.2%. The Psychoticism (P) (51.60 +/- 9.66)
      or Neuroticism (N) (51.57 +/- 10.75) factor score of EPQ in students with test
      anxiety was significantly higher than that in students without test anxiety
      (48.07 +/- 8.62, 45.65 +/- 10.14) (P < 0.001), while the Extroversion or
      Introversion (E) score (50.76 +/- 11.09) was on the contrary (53.68 +/- 11.60) (P
      < 0.01). The total score of TAS was significantly positively related to the P (r
      = 0.14) and N (r = 0.36) factor score and significantly negatively related to the
      E factor score of EPQ (r = -0.15) (P < 0.001). The prevalence of test anxiety in
      introversive students (72.3%) was higher than that in extroversive students
      (53.2%) (P < 0.05), and that in students with unstable emotion (81.4%) and in
      students with apparent psychoticism (84.1%) were also higher than that in those
      with stable emotion (41.0%) and in those without psychoticism (57.7%) (P < 0.01).
      The total score of SES in students with test anxiety (29.12 +/- 4.41) was
      significantly lower than that in students without test anxiety (30.29 +/- 4.25)
      (P < 0.01). The total score of TAS was significantly negatively related to the
      total score of SES (r = -0.23) (P < 0.001). CONCLUSION: Test anxiety should be
      related to the personality and self-esteem, and the prevalence of test anxiety in
      introversive, unstable emotional, apparent psychoticism or low self-esteem
      students should be higher.

PMID- 16620615
TI  - [Currently applied orthodontic techniques: concerns and considerations].

PMID- 16620616
TI  - [Stability of upper molars with the application of implant anchorage].
AB  - OBJECTIVE: To investigate the stability of upper molars with the application of
      micro-screw implant anchorage during orthodontic treatment. METHODS: Fifteen
      adult patients with severe maxillary protrusion were included. Upper first
      premolars were extracted and upper posterior anchorage was reinforced with micro
      screw implant in all patients. The average treatment period to close the
      extraction space was 10.5 months. Cephalometric and cast analysis were carried
      out. RESULTS: During the treatment, the micro-screw implants kept stable in
      sagittal plane; neither the mesial-distal movement nor the rotation or tipping of
      the upper molars during the treatment was of statistic significance (P > 0.05);
      the edge of upper incisors was retracted by 6.99 mm on average, and no
      significant vertical change was observed (P > 0.05). CONCLUSIONS: Micro-screw
      implant could provide good anchorage control in the orthodontic treatment.

PMID- 16620617
TI  - [Uprighting of mesially or horizontally impacted mandibular molars].
AB  - OBJECTIVE: To assess the treatment method and outcome of mesially or horizontally
      impacted mandibular molars. METHODS: Eleven patients with mandibular impacted
      molars, including 9 horizontally impacted molars and 5 mesially impacted molars
      were treated with fixed appliance in conjunction with molar band soldered with
      pushing spring. Crowns of impacted molars were moved occlusally and distally.
      RESULTS: All mesially or horizontally mandibular impacted molars were uprighted
      and brought into occlusion. Mean treatment period was 7.4 months (6 to 12
      months). CONCLUSIONS: This orthodontic molar uprighting technique was effective
      in uprighting and distalizing the impacted molars.

PMID- 16620618
TI  - [Tooth movement in tissue-engineered bone].
AB  - OBJECTIVE: To explore the effect and practical value of repairing the alveolar
      defects with tissue engineering technique and investigate the influence of the
      generated new bone on the orthodontic tooth movement. METHODS: The marrow stromal
      cells of rats were separated, cultured in vitro and induced to osteoblast-like
      cells. The osteoblast-like cells were implanted onto the ceramic bovine bone.
      Then the complex was implanted into the alveolar defect in one side of the rat's
      mandible. The other side of the mandible served as control. Eight weeks later,
      the orthodontic appliances were placed between the first molar and incisors of SD
      rats to move the first molar forward. The tooth movement and root resorption of
      the molar were observed. RESULTS: We found that the tooth movement in the
      experimental area was faster than that in the normal alveolar bone (P < 0.05).
      The root resorption and the alveolar bone height loss were less than that in the
      control area (P < 0.05). CONCLUSIONS: The tissue-engineered bone did not have
      negative influences on tooth movement. The repair of alveolar bone defect by
      tissue engineering approach may be used in craniofacial surgery and orthodontics.

PMID- 16620619
TI  - [First molar extraction in patients with crowding: cases analysis].
AB  - OBJECTIVE: To evaluate the outcome of first molar extraction in patients with
      crowding. METHODS: Totally 22 patients (8 males and 14 females) from Clinic of
      Orthodontics, SUN Yat-sen University School of Stomatology with crowding were
      collected. The patients were aged 11 years 3 months to 26 years 8 months (mean
      age 16 years 6 months). All of them treated with 1 to 4 first molar extractions.
      RESULTS: The average duration of orthodontic treatment was 18.5 months. Normal
      overjet and overbite was achieved. Good functional occlusion was established.
      CONCLUSIONS: Patients with severe crowding could be successfully treated with
      first molar extraction.

PMID- 16620620
TI  - [Summary of the fifth Asian-Pacific Orthodontic Conference].

PMID- 16620621
TI  - [The establishment of a carcinogenesis model of oral squamous cell carcinoma in
      vitro].
AB  - OBJECTIVE: To transform HPV E6/E7 immortalized human oral epithelial cell (HIOEC)
      line cells by benzo(a)pyrene [B(a)P] in vitro, and to establish a carcinogenesis
      model of oral squamous cell carcinoma. METHODS: HIOEC cells were treated with 0.1
      mg/L-1.2 mg/L B(a)P for 6 months. The cells were cloned at 18th passage, and then
      the culture medium was changed into DMEM containing 10% FBS at 21th passage.
      Cells were cultured in vitro for half and one year and the cell line was named
      HIOEC-B(a)P. The morphological changes of the cells were observed with
      differential interference contrast microscope and HE staining. The soft agar
      colony forming ability and tumorigenicity of the cells in nude mice were
      identified to confirm the malignant characteristics of HIOEC-B(a)P cells.
      RESULTS: (1) After HIOEC cells were treated with B(a)P for 6 months, HIOEC-B(a)P
      cells could grow well in DMEM medium containing 10% FBS and physical
      concentration of calcium. (2) When HIOEC cells were treated with chemical
      carcinogens, the morphology of the cells was changed. Cells showed the character
      of polygon epithelial cells with much atypical mitosis. (3) The 93th passage of
      HIOEC-B(a)P cells had soft agar colony formation ability. (4) The 55th passage of
      HIOEC-B(a)P cells could develop parakeratosis mass. The 69th passage of HIOEC
      B(a)P cells could develop typical well-differentiated squamous cell carcinoma.
      The 74th and the 96th HIOEC-B(a)P cells developed I-II grade squamous cell
      carcinoma-like clinical lesions in nude mice. CONCLUSIONS: B(a)P may induce HIOEC
      cells to be oral squamous cell carcinoma (OSCC) carcinogenetic cells. It will
      provide a multiple factors, multistage carcinogenesis model of OSCC for the
      further research.

PMID- 16620623
TI  - [Surgery of the carotid artery: a retrospective study of 35 consecutive cases].
AB  - OBJECTIVE: To retrospectively analyze a single institution's experience with
      surgery of the carotid artery performed as part of an oncological procedure and
      emergency hemostasis, with the aim to determine the preoperative methods for
      evaluation of cerebral circulation, selection of surgical procedures and
      perioperative complications. METHODS: From January 1999 to December 2004, a total
      of 35 patients underwent carotid artery surgery including repair of carotid
      artery in 7 cases, ligation or resection of carotid artery in 17 cases, and
      reconstruction of carotid artery in 11 cases. All the patients were evaluated for
      blood flow in the circle of Willis with DSA, DSA plus TBO plus SPECT, and TCD and
      followed up from 4 months to 4 years. The perioperative complications and
      surgical outcomes were recorded and analyzed. RESULTS: There were 16 carotid body
      tumors, 1 malignant carotid body tumor, 17 malignant tumors involving the carotid
      artery and 1 traumatic arterio-venous fistula. Twenty-seven patients underwent
      carotid occlusion test, 10 were positive and 17 were negative (tolerable). Of 7
      cases with repair of the carotid artery, 1 patient died of uncontrolled bleeding
      due to rupture of the anastomosis, and the remaining was uneventful. Of 17 cases
      with ligation or resection of the carotid artery, 4 developed neurologic deficit
      2 weeks postoperatively. Three patients with malignant tumors died 1 month, 4
      months, and 4 months postoperatively, respectively. One patient with carotid
      artery body tumor complained of inarticulate speech 4 months after operation;
      another patient complained of incapability and limited movement of the
      ipsilateral upper limbs; 5 patients complained of dizziness 4, 6, 12, 24 and 48
      months postoperatively. Of 11 patients who underwent carotid reconstruction, no
      major cerebral complications were noted after operation. One patient died of
      recurrence, 1 patient with carotid body tumor complained inarticulate speech and
      incapability of the contralateral limbs, the remaining was uneventful. Color
      Doppler showed patent vascular graft 1 year postoperatively. CONCLUSIONS: TBO
      plus SPECT is a reliable method for evaluation of the circle of Willis currently.
      The short term and long term complications of ligation of carotid artery are
      high, therefore, resection and revascularization of the carotid artery is
      advocated for carotid artery tumors when possible.

PMID- 16620624
TI  - [Genetic diversity of F-ATPase subunits gene uncA amplified from Streptococcus
      mutans clinical isolates].
AB  - OBJECTIVE: To study the genetic diversity of F-ATPase alpha subunit gene uncA
      derived from Streptococcus mutans (S. mutans) clinical isolates and to
      investigate the relationship between the genetic diversity of acidurance factor
      and S. mutans aciduric ability, also and the cariogenicity. METHODS: Sixty-four
      S. mutans strains derived from 34 caries-active individuals and 30 caries-free
      individuals, including 18 strains displaying high acid tolerance and 20 strains
      displaying low acid tolerance. Gene uncA was amplified with specific primers from
      S. mutans genomic DNA, then the PCR products were analyzed by RFLP and sequenced.
      RESULTS: Two genotypes A and B of PCR-RFLP were revealed when digested with Hph
      I. Mbo II also produced two different pattern C and D. The distributions of A and
      B genotype strains with different caries-sensitivity groups were different (P <
      0.05), and the proportion of A genotype strains from caries-activity group was
      higher than that from caries-free one. The distributions of C and D genotype
      strains with different acidurance strains were different (P < 0.05), and the
      proportion of C genotype strains from high acid tolerance group was higher than
      that from low acid tolerance group. These amplified uncA genes from different
      group were sequenced and there existed variation of Hph I and Mbo II recognized
      sites. CONCLUSIONS: This study indicates that uncA gene of S. mutans F-ATPase
      obviously displayed genetic diversity. The different Hph I-RFLP and Mbo II-RFLP
      genotypes could be related to the cariogenicity and acid tolerance of S. mutans
      strains.

PMID- 16620625
TI  - [A study of the physicochemical and biological properties of mutanase from
      Trichoderma harzianum].
AB  - OBJECTIVE: To determine the physicochemical properties of the mutanase of
      Trichoderma harzianum isolated from China and to study the influence of mutanase
      on the adherence of oral Streptococci and the structure of oral biofilms.
      METHODS: Six fungal strains belonging to Trichoderma were tested for mutanase
      production in the same cultural condition, the strain producing the highest
      mutanase activity was studied further and the pH and temperature optimum of the
      enzyme was determined. The RT-PCR method was used to obtain the gene coding for
      mutanase and the product was cloned to pMD18-T simple vector for sequencing.
      Inhibition effects of mutanase on the adherence of Streptococcus sobrinus OMZ176,
      Streptococcus sobrinus 6715, Streptococcus mutans MT8148 were studied by
      adherence test. The optical sectioning of biofilms with or without mutanase
      supplementation were analyzed by confocal laser scanning microscopy (CLSM).
      RESULTS: The highest enzymatic activity was achieved by Trichoderma harzianum
      Th1, the maximum activity was at pH 5.5 and at 40 degrees C. The nucleotide
      sequence was 92% homology with that of a known gene coding a mutanase (GenBank
      accession No. AJ243799). The adherence of Streptococcus sobrinus OMZ176,
      Streptococcus sobrinus 6715, Streptococcus mutans MT8148 was significantly
      inhibited by mutanase. Compared with control, the biofilms with mutanase
      supplementation had lower height and sparser structure. CONCLUSIONS: The mutanase
      from Trichoderma harzianum Th1 can inhibit the adherence of oral Streptococci and
      had an influence on the structure of oral biofilms.

PMID- 16620626
TI  - [Brain activities during maximum voluntary clenching with and without soft splint
      in patients with hemimasticatory spasms by functional magnetic resonance
      imaging].
AB  - OBJECTIVE: Functional magnetic resonance imaging (fMRI) was used to detect the
      cerebral cortical somatotopy during maximum voluntary clenching with and without
      soft splint in patients with hemimasticatory spasms (HMS) and the central
      mechanisms of HMS and the rule of the splint therapy. METHODS: Four HMS patients
      were selected and the spasms sides were right in two cases and left in the other
      two cases. FMRI images were obtained on Elscint/GE 2.0 Tesla MR system. Block
      design was used and the movement pattern was the onset of spasms after maximum
      voluntary clenching with and without soft splint. The fMRI data were analyzed by
      SPM99 software. RESULTS: With the onset of spasms after maximum voluntary
      clenching, the activation of motor cortex in 3 HMS patients was found lateral
      dominance on the left side, and the other one showed bilateral activation. All
      the 4 patients were found activation in cingulate area. With the onset of spasms
      after maximum clenching wearing soft splints, the activation of motor cortex
      showed no lateral dominance on the left side, and 3 patients were not found
      activation in cingulate area. CONCLUSIONS: The changes of the activation in motor
      cortex and cingulate area during the onset of spasms after clenching with and
      without soft splint might be the central mechanisms of the rule of splint
      therapy, through which the soft splint might function in alleviating muscle pain.

PMID- 16620627
TI  - [PTCH gene mutations in odontogenic keratocysts].
AB  - OBJECTIVE: To investigate the frequency, type and distribution of PTCH mutations
      in odontogenic keratocysts (OKC) and to analyze the molecular pathological
      relationship between sporadic OKC and OKC associated with nevoid basal cell
      carcinoma syndrome (NBCCS). METHODS: Genomic DNA was extracted from 8 cases of
      OKC lesions (4 sporadic OKCs and 4 NBCCS-related OKCs). PTCH gene mutations were
      detected by PCR-direct sequencing. RESULTS: Six novel PTCH mutations were
      identified in 6 out of 8 cases (2 sporadic and 4 NBCCS-related OKCs). Two of
      these were missense mutations leading to substitution of an amino acid residue
      respectively. The other 4 mutations were identified as insertion or deletion
      ranging from one single base to 7 bases, three of which caused frame-shift
      leading to premature truncation of PTCH protein and one resulted in an insertion
      of 2 amino acid residues. All these identified mutations were novel and have not
      been previously described. CONCLUSIONS: PTCH gene mutation is a common event in
      NBCCS-related OKCs and could also be detected in some sporadic OKCs.
      Abnormalities of PTCH gene may be involved in the pathogenesis of OKC.

PMID- 16620628
TI  - [Inhibitory effect of p53 gene on telomerase activity and proliferative activity
      in salivary adenoid cystic carcinoma cells].
AB  - OBJECTIVE: To evaluate the inhibitory effect of p53 gene on salivary adenoid
      cystic carcinoma (SACC) cells. METHODS: Adenoviral vector pDeltaE1-p53 was
      constructed and transfected into SACC-83 cells. The enhanced p53 expression was
      measured by reverse transcription polymerase chain reaction (RT-PCR), and the
      effects of transfected p53 on SACC-83 cells were analyzed by TRAP-PCR-ELISA,
      luciferase reporter, flow cytometry (FCM), soft agar assay and tumorigenicity
      test. RESULTS: The expression of p53 gene in SACC-83 cells was increased after
      introduction of pDeltaE1-p53. The telomerase activity and the transcriptional
      activity of hTERT promoter were inhibited. The cells cycles of transfected SACC
      83 were arrested in G(1) phase and the rate of colony-formation was decreased,
      and similarly the tumorigenicity in nude mice was also decreased. CONCLUSIONS:
      The introduction of wild-type p53 by adenoviral vector could suppress the
      telomerase activity and malignant phenotypes of salivary adenoid cystic carcinoma
      cells.

PMID- 16620629
TI  - [Bone mineral density and biomechanical characters of the augmented alveolar
      ridge by distraction osteogenesis using Ti-Ni shape memory alloy distractor].
AB  - OBJECTIVE: To evaluate the quality of the alveolar ridge augmented by Ti-Ni shape
      memory alloy (Ti-Ni SMA) distractor. METHODS: All of the mandibular premolars and
      the first molars were extracted from 12 adult mongrel canines. One month later,
      box-shaped osteotomy was carried out in the left mandibles and Ti-Ni SMA
      distractors were imbedded. The right sides served as blank control. The canines
      were killed 3 or 6 months later and specimens were taken from corresponding area
      of the experiment sides and the control. Bone mineral density and biomechanical
      function were measured. RESULTS: Bone mineral density, ultimate compressive
      strength and Young's Modules of the augmented ridge were lower than the blank
      control three months after distraction. But the indexes increased and showed no
      significant difference with the control six months after distraction.
      CONCLUSIONS: The canines mandibular posterior alveolar ridge could be augmented
      by distraction osteogenesis using Ti-Ni SMA distractor, and the new bone is
      strong enough for implant placement.

PMID- 16620630
TI  - [Rights maintenance and self-discipline of practicing dentist: Part I. Six
      situations under legalized non-malpractice].

PMID- 16620631
TI  - [How to write medical paper: Part I. Form and methods].

PMID- 16620632
TI  - [Clinical application and basic research of orthodontic implant anchorage].

PMID- 16620633
TI  - [Development of drugs with antiherpetic activity].

PMID- 16620638
TI  - [Challenges in management of cerebral ischemia due to Takayasu's arteritis].
AB  - OBJECTIVE: To explore the management of cerebral ischemia caused by Takayasu's
      arteritis. METHODS: One hundred and three cases treated from 1984 to 2003 were
      reviewed including 92 females. Seven cases underwent ascending aorta to bilateral
      internal carotid artery (ICA) bypass, 38 cases to the axillary artery with graft
      to single ICA bypass. Six cases underwent ascending aorta to axillary bypass with
      3 graft to single ICA bypasses as the second stage surgery. Three cases underwent
      ascending aorta to right ICA bypass with 2 graft to left ICA bypasses as well as
      6 subclavian to carotid bypass, PTA in 5 and stenting in 3 cases, etc. RESULTS:
      Twenty-seven patients with less clinical severity received conservative therapy,
      9 of them had mostly temporarily improvement, 15 had slight improvement or
      basically no change, 1 had hemiplegia and 2 died of stroke and myocardial
      infarction respectively. Surgically, the short-term effective rate was 87% and
      operative death 7.8%. Fifty-five patients were followed up, a mean follow-up time
      was 48 months, and the follow-up rate was 80.9%. The excellently, good, fair, no
      change and death rate were 36.4%, 38.2%, 20.0%, 3.6% and 1.8% respectively. All
      patients with PTA or stent had an immediate good response and all recurred within
      3 to 5 months. CONCLUSIONS: For treating severe cerebral ischemia caused by
      Takayasu's arteritis, the ascending aorta to axillary and single ICA
      reconstruction or the ascending aorta-bilateral axillary bypass for patients with
      subclavian steal syndrome is advocated; second stage operation from graft to
      contralateral ICA can be carried out if necessary.

PMID- 16620639
TI  - [Role of anatomic hepatectomy performed under vascular exclusion in management of
      hepatolithiasis].
AB  - OBJECTIVE: To evaluate the effect of anatomic hepatectomy performed under
      vascular exclusion in management of hepatolithiasis. METHODS: From May 2002 to
      March 2005, fifty-three patients with unilateral hepatolithiasis underwent
      anatomic hepatectomy with exposure and control of inferior vena cava and main
      trunk of hepatic veins. The hepatic lobes involved by hepatolithiasis were left
      lateral lobe (S(2), S(3)) in 12 patients, left lobe (S(2), S(3), S(4)) in 26
      patients, right posterior lobe (S(6), S(7)) in 8 patients and right lobe (S(5),
      S(6), S(7), S(8)) in 7 patients. Atrophy of involved hepatic lobes was found in
      38 patients. Fourteen patients had experienced more than one operation on biliary
      tract. Nine patients showed the symptoms of acute cholangitis preoperatively and
      4 patients complicated with liver abscess. RESULTS: Vascular exclusion was
      successfully performed on all patients to control the blood inflow and outflow of
      liver. The anatomically resected hepatic lobes were left lateral lobe (S(2),
      S(3)) in 12 patients, left lobe (S(2), S(3), S(4)) in 26 patients, right
      posterior lobe (S(6), S(7)) in 8 patients and right lobe (S(5), S(6), S(7), S(8))
      in 7 patients. Except hepatectomy, the additional procedures performed on the
      patients were choledocholithotomy in 39 cases, choledocho-jejunostomy in 5 cases.
      The majority of complications were bile leakage in 3 cases, subphrenic infection
      in 2 cases, hydrothorax in 5 cases and wound infection in 5 cases. CONCLUSIONS:
      Anatomic hepatectomy under vascular exclusion is effective treatment to eradicate
      intrahepatic stone foci in case of unilateral hepatolithiasis, and help to reduce
      intraoperative blood loss and decrease postoperative complications.

PMID- 16620640
TI  - [Surgical management of chronic radiation enteritis].
AB  - OBJECTIVE: To explore the surgical methods and the clinical results of chronic
      radiation enteritis. METHODS: Treatments were applied to forty-nine cases of
      chronic radiation enteritis complicated with intestinal obstruction,
      enterocutaneous fistula, intestinal stenosis, intestinal bleeding, severe
      proctocolitis and intestinal perforation, among whom 47 cases received an average
      of 2.8 +/- 2.1 operations. Twenty-six cases received resection of the injured
      segment with primary anastomosis, fourteen cases received intestinal resection
      and proximal enterostomy, among whom 6 ostomies were permanent, and another 8
      cases received secondary ostomy closure. The injured intestinal segments were
      spared in 7 cases. RESULTS: Forty-seven among 49 cases were cured (success rate,
      96%) with no anastomotic leakage. Two patients died. CONCLUSIONS: Surgical
      complications of chronic radiation enteritis should be managed operatively. The
      operative method should be chosen according to the general condition of the
      patients and the complexity of the abdomen. Perioperative management and proper
      selection of intestinal segments for anastomosis are essential for the success.

PMID- 16620641
TI  - [The diagnosis and treatment for chronic pancreatitis complicated by non
      calculous obstructive jaundice].
AB  - OBJECTIVE: To study the characters of chronic pancreatitis complicated by non
      calculous obstructive jaundice, and discuss the methods for differentiation and
      treatment. METHOD: Twenty cases selected from January 1985 to December 2004 were
      analysed in the fields of differentiation and treatment. RESULTS: All cases
      didn't present with typical clinical presentations and radiological features.
      Jaundice was presented as the main complaint. Stricture of the intra-pancreatic
      common bile duct was the symbolic radiological feature. Pancreatic disseminated
      inflammation was verified pathologically in these cases. CT, ultrasound, EUS,
      ERCP, MRCP and antigen-marker of neoplasm failed to offer the data for
      differentiation. The diagnosis could only be determined by pathological exam. The
      obstructive jaundice could be solved by biliary-enteric anastomoses successfully.
      CONCLUSIONS: The patients with sole complaint of obstructive jaundice account for
      15% of all inpatients with chronic pancreatitis. There exists a direct
      relationship between the jaundice and the pancreatic inflammation. This disorder
      should be differentiated from total pancreatic carcinoma, but few differentiated
      material could be offered by preoperative studies. Pathological result derived
      from the tissue sample obtained within the exploration would be reliable for
      diagnosis. The bypass between biliary tract and intestine would be a safe and
      economical treatment method.

PMID- 16620645
TI  - [Relationship between apoptosis induced by 2-butylamino-2-demethoxy-hypocrellin B
      in human pancreatic cancer cells Capan-1 and photosensitization of mitochondria].
AB  - OBJECTIVE: To explore the possible mechanism of apoptosis induced by photodynamic
      therapy (PDT) in human pancreatic cancer cells Capan-1 with 2-butylamino-2
      demethoxy-hypocrellin B (BAHB) as photosensitizer. METHODS: The localization of
      BAHB in Capan-1 cells was studied, apoptosis was determined by DNA gel
      electrophoresis after PDT. The mitochondria membrane potential (DYm) and
      cytochrome C release were observed by laser scan confocal microscopy and Western
      blotting. RESULTS: The low concentration photosensitizer was mainly localized in
      mitochondria and also in lysosomes when the concentration is high. DNA ladder
      analysis showed characteristic of apoptosis. The mitochondria membrane potential
      (DYm) showed a loss of 30% around, after 6 hours by PDT under laser scan confocal
      microscopy, which is caused by a sudden increase in the permeability of
      mitochondria membrane accompanied with apoptosis. In Western blotting, cytochrome
      C release was observed from the mitochondria into the cytoplasm during BAHB
      induced apoptosis. CONCLUSION: The research suggests that BAHB-induced apoptosis
      is related to photosensitization of mitochondria.

PMID- 16620646
TI  - [Study of growth inhibition of gastric cancer cells by sRNA targeting polo like
      kinase 1 in vitro and vivo].
AB  - OBJECTIVE: To observe the effect of polo like kinase 1 (plk1) gene depletion on
      the growth of gastric cancer cell line-MKN45 cells in vitro and vivo and discuss
      the feasibility and effectiveness of arranging plk1 as gene therapeutic target
      for gastric cancer. METHODS: The plk1 expression of MKN45 cells was inhibited by
      RNA interference (RNAi). The plk1 mRNA and protein level were measured by real
      time quantitative PCR and western blotting, and the change of cell cycle
      distribution and apoptosis rate were detected by flow-cytometry, and the MKN45
      cells proliferation was measured by MTT method. MKN45 cells treated with plk1
      siRNA were transplanted subcutaneously in nude mice and their tumorgenesis
      ability were observed, the plk1 protein levels of the samples from nude mice in
      different groups were compared. RESULTS: After treatment with plk1 siRNA, plk1
      mRNA and protein level decreased obviously in certain time, more MKN45 cells
      accumulated at G(2)/M (P < 0.05). Apoptosis rate of MKN45 cells treated with plk1
      siRNA was higher than that of control cells at 48 h and 72 h (P < 0.05), and
      MKN45 cells proliferated slowly than control groups (P < 0.05), while the
      tumorgenesis ability obviously decreased, but the plk1 protein levels of the
      samples from nude mice in different groups were not different. CONCLUSIONS: siRNA
      targeting plk1 can inhibit the proliferation of MKN45 cells in vitro and vivo.
      Plk1 may be a novel therapeutic target for gastric cancer.

PMID- 16620648
TI  - [Latissimus dorsi transfer to restore thoracic malformation of Poland's
      syndrome].
AB  - OBJECTIVE: To study the methods and points for attention of latissimus dorsi
      muscle flap transplantation to correct the thoracic malformation of Poland's
      syndrome. METHODS: From 1995 to 2003, 10 patients were diagnosed of Poland's
      syndrome with absence of pectoris major muscle in all patients. The latissimus
      dorsi muscle flap was exposed and transferred through a vertical lateral thoracic
      cut and a short cut beneath the axillary fold. Reconstruction of the anterior
      axillary wall is one of the major goals to be achieved in this operation.
      RESULTS: All of the latissimus dorsi muscle flaps survived. Satisfactory outcomes
      were achieved after 1-2 years of follow-up. CONCLUSION: The latissimus dorsi
      muscle flap has a stable and reliable blood supply. It is an ideal muscle flap to
      restore the thoracic malformation of Poland's syndrome.

PMID- 16620649
TI  - [Effect of silver nanoparticle dressing on second degree burn wound].
AB  - OBJECTIVE: To explore the influence of silver nanoparticle dressing on prevention
      of infection and healing of the second degree burn wound. METHODS: One hundred
      and ninety-one burn patients with second degree including superficial and deep
      burn wound were randomly divided into three groups. Group A including 65 cases
      was treated by silver nanoparticle dressing on wounds, and group B (63 cases) and
      group C (63 cases) were treated by 1% silver sulfadiazine cream and vaseline
      gauze on their wounds, respectively. Dressing was changed daily, and wound swab
      bacterial cultures were performed before and after dressing change, and also
      wound healing times were recorded in each patient. RESULTS: Group A and B were
      similar in their bacterium colonizations on wound after treatment with the silver
      nanoparticle dressing and 1% silver sulfadiazine cream, and they had a similar
      effect on reducing bacterium colonization on wound after treatment, while in
      vaseline gauze group bacterium colonization on wound increased after treatment.
      In group A the wound healing time of superficial second degree was significantly
      shorter than those in group B and group C (P < 0.01). In deep second degree
      wounds the healing time in group A was much shorter than that in group C (P <
      0.01), but had no significant difference when compared with group B (P > 0.05).
      CONCLUSION: Silver nanoparticle dressing can be used on second degree burn wound
      and can decrease the risk of wound infection and accelerate wound healing.

PMID- 16620660
TI  - [Clinical experience of simultaneous aortic operation and coronary artery bypass
      grafting].
AB  - OBJECTIVE: To summarized the experience of simultaneous aortic operation and
      coronary artery bypass. METHODS: Between November 1997 and September 2004, thirty
      six patients who underwent combined aortic operation and coronary artery bypass
      graft (CABG) were reviewed with a mean age of (57 +/- 12) years (range 31 to 75).
      Nineteen patients were suffered from aortic dissection. There were 17 patients of
      aortic aneurysm, 5 aortic root aneurysm, 5 ascending aortic aneurysm, 4 aortic
      arch aneurysm, 3 abdominal aneurysm. Preoperational coronary angiography was
      performed in 1 of 10 acute type A dissection patients. The coronary arteries were
      involved by dissection in 7 acute type A dissection patients. The
      artherosclerosis of coronary artery was found during operation in 2 patients.
      Among 7 patients with chronic type A aortic dissection, coronary angiography was
      performed in 2, coronary artery was involved by dissection in 2 and coronary
      arterosclaerosis was founded in 3. There were 2 patients with acute or chronic
      type B aortic dissection. The stenosis of coronary artery was confirmed by
      preoperative angiography in the patients with aortic aneurysm. There were 57
      coronary bypass grafts, 6 of them were artery grafts, and others were venous
      grafts. RESULTS: The mean cardiopulmonary bypass time was (157 +/- 54) min, and
      the mean aortic cross clamp time was (98 +/- 31) min. Five patients with type A
      aortic dissection died postoperatively, 3 from heart failure leading to multi
      organ system failure, 1 from cerebral hernia and one from ischemia of intestinal
      tract. Postoperative complication included reoperation for hemorrhage in 1
      patient, respiratory failure in 1 patient. CONCLUSIONS: Type A aortic dissection
      with coronary involvement or arterosclaerosis is associated with high mortality
      rate. Coronary artery angiography should be performed in the elder than 50 years
      patient with aortic aneurysm. Combined aortic aneurysm operation and CABG is a
      safe procedure.

PMID- 16620661
TI  - [Mean flow of saphenous vein graft and its influencing factors in patients
      performed coronary artery bypass grafting].
AB  - OBJECTIVE: To analyze the mean blood flow of saphenous vein (SV) graft and it's
      influencing factors in off-pump coronary artery bypass grafting by using transit
      time flowmeter (TTFM). METHODS: Three hundred and twenty-six patients were
      studied. After all anastomoses were completed, and hemo-dynamic status was
      stable, TTFM was utilized to measure and record the SV flow wave, pulsatility
      index (PI), value of mean flow, diastolic and systolic peak flow, vascular
      resistance, insufficiency ratio and mean blood pressure. The standard conditions
      of good graft status to define the normal mean flow included good diastolic
      augmentation of blood wave, PI less than 5, intraoperative and postoperative no
      significant change in electrocardiogram, and smoothly postoperative recovery.
      RESULTS: Total mean flow calculated from that of all patients was (39 +/- 23)
      ml/min (10-153 ml/min). Majority mean value (60.1%, 196/326) was in the range of
      20-50 ml/min. Statistics showed that mean flow was significantly related to
      vascular resistance and diastolic peak flow and PI rather than the other factors
      (r was -0.95, 0.77 and -0.51 respectively). CONCLUSIONS: For the patients, over
      15 ml/min mean flow of SV graft is acceptable, and over 35 ml/min is
      satisfactory. The diastolic peak flow and vascular resistance are two important
      factors influencing mean flow.

PMID- 16620662
TI  - [Pathological changes of radial artery used for coronary artery bypass grafting
      and its related risk factors for intimal hyperplasia].
AB  - OBJECTIVE: To examine the degree of intimal hyperplasia and the prevalence of
      atherosclerosis in radial arteries taken from the patients undergoing coronary
      artery bypass grafting (CABG), and to analyze the risk factors to obtain some
      helpful information for choosing arterial conduits. METHODS: Forty-one radial
      arteries and 11 internal mammary arteries samples were collected. The average age
      of patients was 48.5 years, and they all were male. Intimal hyperplasia,
      atherosclerosis, medial calcification were evaluated by routine histological
      methods, and the severity of diseases was measured on the percentage of luminal
      narrowing and the intima-to-media ratio (the intima area/media area). The risk
      factors for coronary heart disease were also analyzed. RESULTS: Ninety-three
      percent (38 of 41) of radial arteries showed mild intimal hyperplasia, which was
      not regarded to influence blood flowing after CABG. As a part of them, 54%
      (22/41) of radial arteries had a lower than 25% of luminal narrowing, meanwhile
      39% (16/41) of radial arteries had the percentage of luminal narrowing between
      25% and 50%. Only 7% (3 of 41) of radial arteries were found to have occlusive
      lesions, which made arterial lumen decreased more than 75%. The 3 patients
      including 2 with severe atherosclerosis and another 1 aged 17 years was involved
      by fibromuscular dysplasia. The later vessel was discarded after harvesting. The
      percentage of luminal narrowing and the intima-to-media ratio were higher in
      radial artery than that in internal mammary artery (t = 3.00, 2.49, P < 0.05).
      The two parameters were positively correlated with age (r = 0.398, 0.310, P <
      0.05), but this study failed to show any relationship between intimal hyperplasia
      of radial artery and coronary lesions and other risk factors. Medial
      calcification was not found by routine histological method in all cases.
      CONCLUSION: Only mild intimal hyperplasia and no medial calcification are found
      in radial arteries used for CABG in the patients. Because the risk factors could
      not yet predict the severity of radial arterial lesions, this study strongly
      suggests that the Doppler ultrasonography and pre-operation clinical
      consideration should be emphasized to screen out some arteries with occlusive
      lesions.

PMID- 16620663
TI  - [Clinical analysis for 232 cases of primary heart neoplasms].
AB  - OBJECTIVE: To summarize the clinical characterizations and outcome of surgical
      treatment of primary heart neoplasms. METHODS: The clinical data of cardiac
      neoplasms were analyzed retrospectively in 232 patients. There were 14 malignant
      tumors (6.0%) and 218 benign tumors (94.0%), of which 200 were left atrial
      myxomas (86.2%). Palpitation and dyspnea on exertion added up to 87.1% (202/232)
      of all clinical symptoms. Two hundred and twenty-three out of 230 patients
      underwent complete removal of the tumors, remaining 2 patients had partial
      removal. Five patients received biopsy only. Other procedures had done in the
      same stage including 5 cases with mitral valve replacement, 1 case with pulmonary
      arterial valve replacement, 5 cases with thrombectomy through the Fogarty
      catheter. RESULTS: Two cases died preoperatively operation. Three cases died
      intraoperative operation. One hundred and eighty-five cases were followed up for
      6 months to 24 years, of which 10 malignant tumors died in 1 year and 1 malignant
      case recurred after 4 months. Of 174 benign neoplasms, 1 case recurred and 10
      cases were dead, remaining were cured. CONCLUSIONS: Left atrial myxomas are most
      commonly seen in patients with primary heart neoplasms. Palpitation and dyspnea
      on exertion are the most frequent symptoms. It is suggested that the patients
      should accept surgical treatment as soon as possible once the diagnosis is
      confirmed. Surgical treatment is effective for the benign cardiac tumors.
      Prognosis is poor in patients with malignant cardiac tumors.

PMID- 16620664
TI  - [Fluorine-18 fluorodeoxyglucose uptake in patients with benign pulmonary
      nodules].
AB  - OBJECTIVE: To assess the features of fluorine-18 fluorodeoxyglucose (FDG) uptake
      in patients with benign pulmonary nodules. METHODS: From October 1998 to July
      2004, 47 patients with benign pulmonary nodules were imaged with FDG-positron
      emission tomography (PET). Diagnoses were confirmed by surgery. FDG-PET data was
      analyzed by visual method and semi-quantitive method. When pulmonary nodules with
      abnormal FDG intake appeared in PET scans confirmed by visual method, their
      maximum and mean standard uptake value (SUVmax and SUVmean) and SUV of normal
      lung (SUVlung) were measured using semiquantitative method. RESULTS: Twenty-one
      cases showed nothing abnormal in PET scans, including 17 calcification and
      fibrosis, 2 hamartomas and 2 sclerosing hemangiomas. 26 pulmonary nodules were
      detected by FDG-PET (17 active tuberculous, 6 inflammatory pseudotumors, 3
      cryptococcosis). FDG uptake of these 26 nodules was higher than that of normal
      lung (SUVmax, SUVmean and SUVlung were 3.04 +/- 1.65, 2.48 +/- 1.35 and 0.40 +/-
      0.07, respectively, P < 0.001). Correlations were not found between FDG uptake
      and nodule size or SUV of normal lung or age or blood glucose level in these 26
      patients (P > 0.05). SUV in 9 cases (9/26, 35%) were beyond 2.5. CONCLUSIONS:
      Some benign pulmonary nodules were FDG avid.

PMID- 16620665
TI  - [Long-term outcome of antireflux surgery for gastroesophageal reflux disease].
AB  - OBJECTIVE: To investigate the long-term outcomes of various antireflux procedures
      for gastroesophageal reflux disease (GERD). METHODS: Between November 1988 and
      January 2004, 129 patients with GERD underwent antireflux procedures. Six kinds
      of antireflux procedures were performed including Nissen fundoplication, cardiac
      oblique invagination (COI) procedure, Belsey Mark IV, Toupet, Thal and Dor
      procedures. One hundred and sixteen patients were followed up. Esophageal
      manometry study was carried out in 95 patients preoperatively and 51
      postoperatively. 24-hour esophageal pH monitoring were carried out in 56 patients
      preoperatively and 35 postoperatively. Esophagoscopy were performed in all
      patients before operation and 48 cases after operation. RESULTS: Clinical symptom
      scores reduced significantly from 4.1 +/- 0.4 before surgery to 1.1 +/- 1.0 after
      surgery (t = 27.21, P < 0.01). The outcome of surgery showed excellent in 42
      cases (36.2%), good in 60 (51.7%), fair in 7 (6.0%), poor in 7 (6.0%). The long
      term follow-up showed excellent or good results in 87.9% of patients. There was
      no significant difference in Nissen fundoplication, COI procedure and Belsey Mark
      IV. CONCLUSIONS: There are significant differences in symptom score, esophageal
      manometry, 24-hour esophageal pH monitoring and esophagoscopy pre- and post
      operatively. There is no significant difference in Nissen fundoplication, COI
      procedure and Belsey Mark IV.

PMID- 16620666
TI  - [Clinical diagnosis and surgical treatment of primary pulmonary lymphoma].
AB  - OBJECTIVE: To study the clinical characteristics, the principles of diagnosis and
      surgical treatment for primary pulmonary lymphoma. METHOD: Ten patients with
      primary pulmonary lymphoma were treated surgically and their clinical
      characteristics, the experiences of clinical diagnosis and surgical treatment
      were analyzed. The tumors located in left upper lobe in 2, left lower lobe in 1,
      right upper lobe in 3, right middle lobe in 3 and right lower lobe in 1. The main
      symptoms were cough and (or) hemoptysis. Imageological representations (X-ray and
      CT scanning of thorax) were similar to primary pulmonary carcinoma. Broncho
      fibroscopic examination was performed on all cases with negative findings. Eight
      cases were mistakenly diagnosed as primary pulmonary carcinoma by imageological
      representations. Only 2 cases were diagnosed as primary pulmonary lymphoma by
      percutaneous needle biopsy and pathologic examination. All cases received
      pneumonectomy, ipsilateral hilar and mediastinal lymphadenectomy. All cases with
      non-Hodgkin's lymphoma received regular chemotherapy (MOPP and ABVD scheme for 1
      case with Hodgkin's disease respectively, CHOP for 8 cases with non-Hodgkin's
      lymphoma), and 3 cases received radiotherapy postoperatively. RESULTS: Eight
      cases were non-Hodgkin's lymphoma (B-type) and 2 cases were Hodgkin's disease
      (mixed type) confirmed by pathological examination. Six cases with non-Hodgkin's
      lymphoma (3 cases for stage IE, 2 cases for stage II 1E, and 1 case for stage II
      2E W) had been surviving for 18-42 months until the follow-up. Two cases with non
      Hodgkin's lymphoma (stage II 2E, B-cell, low-grade) and 2 cases with Hodgkin's
      disease (stage IE and II 2E, mixed type) died in 24, 32, 8 and 17 months
      postoperatively respectively. CONCLUSIONS: Primary pulmonary lymphoma is a rare
      type of malignant lung neoplasm without special clinical features. The
      preoperative diagnosis is difficult. Treatment modalities include surgical
      treatment, radiotherapy and regular chemotherapy postoperatively.

PMID- 16620670
TI  - [The clinical study of 120 cases total cystectomy and W shape orthotopic ileal
      neobladder].
AB  - OBJECTIVE: To study advantages or disadvantages of total cystectomy and W shape
      orthotopic ileal neobladder. METHODS: Radical cystectomy and ileal new bladder
      was performed antegradly and retrogradly for 120 male patients. For the
      construction of the reservoir, the 40 cm ileal segment was isolated along its
      antimesenteric border and then arranged into a W shape. The incised ileum was
      sutured blanketly to create urine bag. The ureters were replanted at the two
      corners of the W shape by way of creating nipple. RESULTS: The first 50 cases
      took 210-300 min with a mean of 270 min. The later 70 cases took 110-205 min with
      a mean of 143 min. Ninety-one of 120 cases had been followed up for 2-88 months
      with a mean of 30 months. Eighty-five cases had achieved excellent daytime
      continence, whereas 71 cases had nighttime continence. There were 9 cases of
      hydroureter and 2 cases of moderate hydronephrosis. Renal function of 2 cases
      were slightly abnormal. Hypokalemia occurred in 6 cases, and there was no
      metabolic-disorder. On voiding cystography, only 1 case showed reflux in right
      ureter. Only 2 case suffered from cancer recurrence of urethral and no patient
      suffered from cancer recurrence of neobladder. Twenty patients were evaluated by
      urodynamic examine. The urine flow curve showed continual shape in 12 cases,
      while intermittent shape in 8 cases. Voiding cystourethrography showed the
      neobladder outlet presented funnel shape and open well in continual group, while
      lack of funnel shape or bladder neck opened badly in intermittent group.
      CONCLUSION: The modified total cystectomy and ileal new bladder are effective and
      reliable treatment for patients.

PMID- 16620671
TI  - [Diagnosis and treatment of interstitial cystitis: report of 16 misdiagnosed
      cases].
AB  - OBJECTIVE: To investigate the diagnoses and treatment of interstitial cystitis
      (IC). METHODS: The clinical data of 16 IC patients were analyzed respectively.
      The patients with urinary frequency, urgency, suprapubic pain and chronic pelvic
      pain. They were misdiagnosed as chronic cystitis, pelvic inflammation,
      endometriosis, cystophthisis and urethral syndrome, and were diagnosed finally by
      the means of pathology or cystoscopy. Among the 16 patients, 4 cases had the
      operation of ileal reservoir, Two cases had sigmoid-cysto-plasty, and 10 cases
      had drug treatment. The methods of IC diagnosis and treatment were discussed with
      the review of literature. RESULTS: The pelvic ache disappeared completely in 4
      cases after the operation of ileal reservoir; Two cases after cystoplasty felt
      lightly discomfortable in perineum occasionally, and their bladder capacity was
      above 350 ml, no recurrence after operation having been found after follow-up for
      24 months and 33 months; Ten cases treated with non-operative treatment improved
      obviously, with the O'Leary-Sant IC symptom index and IC problem index decreased
      from 15.4 +/- 4.1, 9.4 +/- 2.7 to 4.1 +/- 2.1 and 5.1 +/- 3.9, respectively.
      CONCLUSIONS: Sufficient attention should be paid to the diagnosis and
      differential diagnosis of IC; Early diagnosis and therapeutic alliance with
      manifold measures can relieve the patients' symptom and improve the quality of
      life.

PMID- 16620672
TI  - [The detection of protein expression of clusterin and Ki-67 and the status of
      cell apoptosis in bladder transitional cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of clusterin protein in bladder
      transitional cell carcinoma (BTCC) and it's association with tumor cell
      proliferation and apoptosis. METHODS: A tissue microarray (TMA) containing 87
      informative cases of BTCCs was constructed firstly. The methods of
      immunohistochemistry and terminal deoxynucleotidyl transferase-mediated nick end
      labeling were then used to examine the expression of clusterin and Ki-67 protein
      and the status of cell apoptosis in BTCC, respectively, and the correlations
      between different markers and the clusterin expression associated with patients'
      clinico-pathological features were evaluated. RESULTS: In TMA of 87 BTCCs, 37
      (43%) cases were observed overexpression of clusterin. A significant association
      of clusterin expression with BTCC's pathological grade, as well as with tumors
      clinical stage was observed (P < 0.01), where the frequency of overexpression of
      clusterin in poor differentiated BTCCs (G(3), 71%) and tumors in more advanced
      stage (T(2-4), 62%) was significantly higher than that in well differentiated
      BTCCs (G(1-2), 29%) and tumors in early stage (T(a-1), 28%). In addition, a
      significant correlation between clusterin expression and tumors apoptotic index
      (AI) was evaluated (P < 0.01), in which 57% of BTCCs with overexpression of
      clusterin were observed a lower AI, while 72% of tumors with normal expression of
      this protein showed a higher AI, but no correlation between clusterin and Ki-67
      expression. CONCLUSIONS: The overexpression of clusterin is associated positively
      with BTCC's malignant clinical phenotypes including tumor's differentiation and
      invasive depth, and it is correlated inversely with AI of tumor cells.

PMID- 16620673
TI  - [Anesthetic management of laparoscopic adrenalectomy for pheochromocytoma].
AB  - OBJECTIVE: To investigate the anesthetic management features of laparoscopic
      adrenalectomy for pheochromocytoma. METHODS: Twelve patients scheduled for
      laparoscopic adrenalectomy for pheochromocytoma under general anesthesia were
      allocated into group 1, while another 12 patients who received transabdominal
      adrenalectomy for pheochromocytoma under general anesthesia were selected as
      group 2. The hemodynamic changes and the postoperative recovery profiles between
      the two groups were compared. RESULTS: Hemodynamic fluctuation occurred during
      carbon dioxide insufflation and tumor manipulation in group 1. However, there
      were no differences between the two groups. Duration of post operative recovery
      and hospital stay as well as requirement of analgesics in group 1 were
      significantly lower than those in group 2 (P < 0.05). CONCLUSION: Hemodynamic
      fluctuation still exists during laparoscopic adrenalectomy for pheochromacytoma.
      However, patients undergoing such surgical procedure recover faster as compared
      with open surgery.

PMID- 16620680
TI  - [Choice of the surgical approach to petroclival tumor].
AB  - OBJECTIVE: To discuss the reasonable choice of the surgical approach to
      petroclvial tumors. METHODS: The clinical data of consecutive 53 patients with
      the petroclival tumors, treated from June 2002 to June 2004, were reviewed to
      compare the different surgical approaches to pertroclival region. RESULT:
      Subtemporal transtentorial approach were used in 11 patients, suboccipital
      retrosigmoid approach in 12 patients, (transzygomatic or orbitozygomatic)
      frontotemporal (pterional) approach in 12 patients, presigmoid sinus approach in
      2 patients, subtemporal and retrosigmoid sinus combined approach in 7 patients,
      subtemporal anterior petrosal extradural approach in 7 patients and extended
      transfrontal base extradural approach in 2 patients. Of all patients in this
      group, total tumor removal was achieved in 32 patients, subtotal in 9, largely
      partial in 12. The new cranial nerve deficit took place in 16 patients
      postoperatively, two patients died from coma and serious pneumonia. CONCLUSIONS:
      Using perfect microsurgical technique, conventional surgical approaches on
      petroclival region such as suboccipital retrosigmoid approach, subtemporal
      transtentorial approach can be suitable for most petroclival tumor with the help
      of neuro-navigation and neuro-endoscopy. To the epidural tumor on petroclival
      region, the epidural approach should be used with less invasion to the brain
      tissue. And to the giant petroclival tumor, the combined-tentorial approach can
      provide an excellent access and exposure to the tumor.

PMID- 16620691
TI  - Current status and perspective of percutaneous coronary intervention in China.

PMID- 16620681
TI  - [Different methods of intracranial-extracranial bypass surgery for the treatment
      of intracranial aneurysms].
AB  - OBJECTIVE: To investigate the effects and methods of intracranial-extracranial
      (IC-EC) bypass surgery in the treatment of intracranial aneurysms. METHODS: The
      clinical material of 9 cases, who performed IC-EC bypass surgery before occlusion
      of the parental arteries of intracranial aneurysms, was studied retrospectively,
      especially how to evaluate the co-lateral circulation of the parental arteries
      and how to select the different methods of IC-EC bypass surgery. RESULTS: The co
      lateral circulation in 9 cases was not enough to meet the need of the cerebral
      blood flow after occlusion of the parental arteries of the aneurysms.
      Revascularization by different methods of IC-EC bypass surgery and then occlusion
      of the parental arteries, ischemia in the brain area feeding by occluded parental
      arteries of the aneurysms did not occurred. CONCLUSION: When the co-lateral
      circulation of the parental arteries of intracranial aneurysm is not enough, the
      revascularization by different methods of IC-EC bypass surgery is needed before
      occlusion of these arteries.

PMID- 16620692
TI  - A single center investigation of bare-metal or drug-eluting stent restenosis from
      1633 consecutive Chinese Han ethnic patients.
AB  - BACKGROUND: Stents are widely used in China but the clinical impression is
      somehow that restenosis is less common because of the lower prevalence of
      coronary artery disease (CAD) and associated risk factors in Chinese populations.
      However, no large-sample published studies are available on angiographic stent
      restenosis including those of bare-metal stent (BMS) or drug-eluting stent (DES)
      in Chinese Han ethnic population. METHODS: A total of 1633 consecutive patients
      with CAD who had undergone coronary stenting, quantitative coronary angiography
      (QCA) were retrospectively studied. At the time of stent implantation and at 7
      months post-stenting 675 patients had a follow-up angiography. Statistical
      analysis was made with the chi-square test for categorical variables, unpaired t
      test for continuous variables, univariate or multivariate regression for baseline
      and angiographic characteristics and the Kaplan-Meier method for rate of target
      lesion revascularization (TLR). RESULTS: Stent restenosis was defined as > or =
      50% diameter stenosis in the dilated segment. A total of 675 patients with 1074
      lesions were subjected to angiographic follow-up for 7 months on average. Of
      these lesions, 448 were implanted with BMS whereas 626 lesions with DES. At 7
      months, bare-metal in-stent restenosis occurred in 148 lesions (33.0%), and bare
      metal in-segment restenosis in 155 lesions (34.6%) in contrast to drug-eluting in
      stent restenosis in 48 lesions (7.7%) and drug-eluting in-segment restenosis in
      73 lesions (11.7%) (P < 0.001 compared with BMS respectively). Late loss in both
      in-stent and in segment was higher in BMS than in DES groups [(1.00 +/- 0.69) vs
      (0.28 +/- 0.52); (0.78 +/- 0.71) vs (0.21 +/- 0.52), P < 0.001 respectively].
      Angulated lesion, lesion length, pre-procedural minimal luminal diameter (MLD),
      and BMS were independent predictors for TLR, (P < 0.01 respectively), whereas
      current smoker, ostial lesion, and stent overlapping, post-procedure in-stent
      MLD, lesion length, and stent types were independent predictors for in-segment
      restenosis (P < 0.01 respectively). Standard coronary risk factors such as
      hypertension, hyperlipidemia, diabetes, and history of CAD were not associated
      with a higher rate of restenosis caused by BMS or DES implantation in our Chinese
      Han ethnic population. CONCLUSIONS: Coronary stenting including BMS or DES
      implantation in Chinese Han ethnic patients is associated with a restenosis rate
      comparable to that demonstrated in previous studies from the western countries,
      and predictors of stent restenosis are somehow different from those in the
      western population.

PMID- 16620693
TI  - Frequency of infarct-related artery with myocardial bridging in patients with ST
      elevation myocardial infarction and its impact upon percutaneous coronary
      intervention.
AB  - BACKGROUND: Myocardial bridging (MB) as a congenital condition with a reported
      frequency of 5% - 12% in diagnostic coronary angiography may be an important
      factor causing myocardial ischemia. However, its frequency in the infarct-related
      artery (IRA) of patients with ST-elevation myocardial infarction (STEMI) and the
      impact upon percutaneous coronary intervention (PCI) remain undetermined. In this
      study, we investigated MB frequency and its impact upon primary PCI in patients
      with STEMI. METHODS: The data of coronary angiography for 554 consecutive
      patients with STEMI who had undergone successful primary PCI were retrospectively
      analyzed to identify a frequency of MB in the IRA and its association with gender
      and age. According to the angiographic findings, the patients were divided into
      MB patients and non-MB patients. The endpoints of this study included immediate
      angiographic findings after primary PCI and 6-month major adverse cardiac events
      (MACE) (death, recurrent myocardial infarction, target lesion or vessel
      revascularization) between the MB patients and the non-MB patients. RESULTS: A
      frequency of MB in the IRA of 46 patients (8.3%) was identified in this series;
      it was more common in patients > or = 65 years old (36/206) than in those < 65
      years old (10/348) (17.5% vs 2.9%, P < 0.001). The trend of MB in the IRA was
      observed more frequently in women without significant difference than in men
      (10.2% vs 7.8%). TIMI grade III flow was achieved in 91.9% (509/554) of all
      patients following primary PCI, in 60.9% (28/46) of the MB patients and in 94.7%
      (481/508) of the non-MB patients respectively (P < 0.001). The in-hospital
      mortality was 4.7% (26/554) in this series including 13.0% (6/46) of the MB
      patients and 3.9% (20/508) of the non-MB patients (P < 0.001). A significant
      difference in 6 months MACE was seen between the MB patients (19%) and the non-MB
      patients (6.2%) (P < 0.001). CONCLUSIONS: MB in the IRA is relatively common in
      elderly patients with STEMI with a more evident trend in women, suggesting that
      arteriosclerosis and plaque rupture occurs more easily in the proximal artery to
      MB than in younger patients. Poor TIMI grade flow in patients with MB in the IRA
      after primary PCI may contribute to a high in-hospital mortality rate (13%) and 6
      month MACE (19%) in the MB patients.

PMID- 16620694
TI  - Efficacy of stenting for unprotected left main coronary artery disease in 297
      patients.
AB  - BACKGROUND: Angioplasty in the unprotected left main coronary artery (LMCA) has
      been controversial. This study aims to evaluate the safety and clinical
      effectiveness of stenting, including bare metal stent and drug eluting stent
      (DES), for treatment of unprotected LMCA disease. METHODS: Between September 1997
      and December 2005, a total of 297 consecutive patients underwent percutanous
      coronary intervention (PCI) on LMCA lesions in our hospital. Their in-hospital
      data and clinical follow-up outcomes were analyzed and those in pre-DES "era"
      (group I, from September 1997 to December 2002) were compared with those in DES
      "era" (group II, from January 2003 to December 2004. Patients in 2005 for the
      time of follow-up less than one year were not included in this group). RESULTS:
      Altogether 368 coronary stents were successfully deployed in 295 patients. Stents
      failed to be implanted after balloon predilation in two patients, who received
      coronary artery bypass graft (CABG) successfully. Bifurcation techniques for
      distal LMCA executed in 206 patients (69.4%, 206/297), included crossover
      stenting in 156 (75.7%), T stenting in 4 (1.9%), provisional T stenting in 28
      (13.6%), kissing stenting in 5 (2.4%) and stent crushing in 13 (6.3%) patients.
      During their hospital stay, 5 (1.7%) patients died after PCI procedure, of which
      4 died from cardiac origin and one of renal failure. The total in-hospital major
      adverse cardiac events (MACE) were 2.0% (6/297). In the follow-up period, 19
      patients (6.5%) died [15 (5.1%) of cardiac death and 4 of non-fatal myocardial
      infarction (MI)]. Besides, 2 (0.7%) developed subacute thrombosis (SAT) and 16
      (5.4%) performed target lesion revascularization (TLR). The total follow-up MACE
      was 14.5% (43/297). Further analysis also showed that, compared with patients in
      group I, those in group II apparently had more multi-vessel involvement (14.7% vs
      81.9%, P < 0.001), and more bifurcation lesions (32.4% vs 72.2%, P < 0.001).
      After PCI, in-hospital MACE of group II was significantly lower than that in
      group I (1.1% vs 9.4%, P < 0.05). And the incidences of MACE, TLR and
      angiographic restenosis in group II were all significantly lower than those in
      group I (all P < 0.05) after one year follow-up. CONCLUSIONS: As new PCI
      strategies and intervention devices such as DES are developed, coronary stenting,
      which might have brought better in-hospital and long-term outcomes than CABG, are
      proved to be technically successful and can be safely applied for the treatment
      of LMCA lesions in the experienced center for coronary intervention.

PMID- 16620695
TI  - Pulmonary vein tachycardia after pulmonary vein isolation in patients with atrial
      fibrillation.
AB  - BACKGROUND: Pulmonary vein (PV) isolation has been developed to treat patients
      with atrial fibrillation (AF), and the electrophysiological endpoint of PV
      isolation is the disappearance or dissociation of pulmonary vein potentials
      (PVPs). Pulmonary vein tachycardia (PVT) is the dissociated PV rhythm with a
      rapid rate. However, the characteristics and significance of PVT after pulmonary
      vein isolation in patients with AF remains unclear. METHODS: From June 2003 to
      June 2005, a total of 285 consecutive patients with drug refractory AF were
      included in this study, and they underwent segmental pulmonary vein ablation
      (SPVA) or circumferential pulmonary vein ablation (CPVA). PV isolation was the
      initial endpoint for both approaches with documenting disappearance or
      dissociation of PVPs. PVT was characterized as dissociated activities within PVs
      with a circle length (CL) of < 300 ms, and was classified into organized PVT or
      disorganized PVT according to the variance of CL. Systematic follow-up was
      conducted after initial procedures. Continuous variables were analyzed by
      Student's t test and categorical variables were analyzed by chi-square test.
      RESULTS: Three hundred and fifteen PVs were ablated in 85 patients underwent SPVA
      approach, 400 circular lesions surrounding ipsilateral PVs (including 790 PVs)
      were produced in the rest of 200 patients received CPVA approach. Electrical
      isolation was achieved in all of these PVs. Of these, PVPs were abolished in
      89.8% (992/1105) of the ablated PVs, dissociated PV rhythms were documented in
      the rest 10.2 % (113/1105) of the treated PVs. Among the 113 dissociated PV
      rhythms, 28 met the criteria of PVT with mean CL of (155 +/- 43) ms (2 PVTs in 2
      patients received SPVA, 26 PVTs in 18 patients underwent CPVA). PVT was more
      frequently documented in patients underwent CPVA approach [9.0% (18/200) vs 2.3%
      (2/85), P = 0.04]. During the 6-month follow-up, it was indicated that no
      significant difference existed in AF free rate between patients with PVT and
      those without PVT (P = 0.75). CONCLUSIONS: PVT dissociated from LA activations
      can be documented after PV isolation, especially in patients underwent CPVA
      approach. However, PVT does not affect the follow-up results.

PMID- 16620696
TI  - Incidence and causes of inappropriate detection and therapy by implantable
      defibrillators of cardioversion in patients with ventricular tachyarrhythmia.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) is the only effective
      therapy in patients with life threatening ventricular arrhythmias. Inappropriate
      detection and therapy by ICDs are the most common causes of side effects that
      affect the quality of life in ICD recipients. This study evaluated the incidence
      and causes of inappropriate detection and therapy by ICDs in patients in our
      hospital. METHODS: From January 2000 to December 2005, fifty patients who
      received ICD implantation for ventricular arrhythmias for prevention of sudden
      cardiac death were evaluated in this study. Each ICD was programmed using
      clinical arrhythmic and cardiac data of the patient before discharge. Patients
      were followed up by standard schedule after implantation and all data retrieved
      from each device were collected and saved for further analysis. RESULTS: No
      arrhythmic event was detected in 12/50 (24%) patients during the period of follow
      up. Among the remaining patients, 11 (22%) experienced inappropriate detections
      and therapies during follow-up in this study. ICD detected 383 ventricular
      tachyarrhythmia (VT) and 108 ventricular fibrillation (VF) episodes and delivered
      678 therapies. In VT group, ICD delivered 413 antitachycardiac pacings (ATPs) and
      118 shocks, among which 78 ATPs and 9 shocks were initiated by 55/383 (14.3%)
      inappropriate detections. In VF group ICD delivered 147 shocks, among which 56
      shocks were initiated by 28/108 (26.9%) inappropriate detections. Overall, more
      than 50% of these episodes were caused by atrial fibrillation (AF) with rapid
      ventricular response, followed by electromagnetic or myopotential interference.
      In addition, most inappropriate therapies occurred within one year after ICD
      implantation. CONCLUSIONS: About one fifth of patients experienced ICD
      inappropriate detection and therapy after implantation. The main cause was AF
      with rapid ventricular response, followed by electromagnetic or myopotential
      interference.

PMID- 16620697
TI  - Compensatory enlargement in transplant coronary artery disease: an intravascular
      ultrasound study.
AB  - BACKGROUND: It is unclear to what extent the "Glagov phenomenon" occurs in
      transplant coronary artery disease (TCAD). The objective of this study was to
      evaluate the relationship between intimal hyperplasia and compensatory
      enlargement in TCAD. METHODS: Intravascular ultrasound imaging was performed on
      190 cardiac transplant recipients at (1.4 +/- 0.6) months and again (12.1 +/-
      0.7) months after cardiac transplantation. Studies 1 year apart were matched at
      625 sites. There were 345 coronary artery sites that had an increase in intimal
      area > 10% from baseline to one year, and this comprised the data set of the
      present study. RESULTS: At the first year, 91% of coronary artery sites with
      intimal growth had a total cross-sectional area stenosis < or = 40%, but 38% of
      the sites showed a decrease of > 10% in lumen area. Receiver operating
      characteristic curve demonstrated that the change in cross-sectional area
      stenosis cut-off level at year 1 was 8% with a sensitivity of 75% and a
      specificity of 82% in predicting lumen loss. At a total cross-sectional area
      stenosis of 20%, sensitivity was 65% with a specificity of 81% in predicting
      lumen loss. CONCLUSIONS: In TCAD, vessel enlargement as a compensatory mechanism
      for plaque growth is generally inadequate. Instead of continued vessel expansion,
      luminal narrowing develops when there is more than 8% cross-sectional area filled
      with intimal hyperplasia. In distinction to native coronary artery
      atherosclerotic disease, the transition point in transplant vasculopathy where
      the lumen is diminished by increasing intimal growth, occurs at a lower
      threshold, 20% vs 40% of vessel cross-sectional area.

PMID- 16620698
TI  - cDNA macroarray for analysis of gene expression profiles in prostate cancer.
AB  - BACKGROUND: Early diagnosis and timely treatment are important for improving
      therapeutic efficiency of prostate cancer. DNA array is a new bio-technology for
      disease diagnosis. This study was conducted to diagnose prostate cancer with cDNA
      macroarray and analysis gene expression profiles of some selective genes in
      prostate cancer. METHODS: Total RNA was isolated from patients with prostate
      cancer and from normal people, and poly (A) RNA was further purified. Then it was
      analyzed for differentially expressed genes in prostate cancer and normal
      prostate by cDNA macroarray system. RESULTS: There were different expressions in
      the nine prostate-associated specific genes in prostate cancer as compared with
      normal prostate, in which, 7 were significantly upregulated and 2 were down
      regulated. CONCLUSION: As a diagnostic approach at molecular level, the cDNA
      macroarray is an effectively diagnostic method for prostate cancer.

PMID- 16620699
TI  - Role and mechanism of rosiglitazone on the impairment of insulin secretion
      induced by free fatty acids on isolated rat islets.
AB  - BACKGROUND: Prolonged exposure of pancreatic beta-cells to fatty acids increases
      basal insulin secretion but inhibits glucose-stimulated insulin secretion.
      Rosiglitazone is a new antidiabetic agent of the thiazolidinediones. However, the
      relationship between thiazolidinediones and insulin secretion is highly
      controversial. The aim of this study is to explore the effect and mechanism of
      rosiglitazone on insulin secretion of islets under chronic exposure to free fatty
      acids (FFA). METHODS: Pancreatic islets were isolated from the pancreata of male
      Sprague-Dawley rats by the collagenase digestion and by the dextran gradient
      centrifugation method. The purified islets were cultured in the presence or
      absence of rosiglitazone and palmitate for 48 hours. The insulin secretion was
      measured by radioimmunoassay. The mRNA level of peroxisome proliferator-activated
      receptor gamma, uncoupling protein 2 (UCP-2) and insulin were determined by real
      time polymerase chain reaction (PCR). The cell cytotoxicity assay was measured by
      cell counting kit-8. RESULTS: Islets exposed to elevated palmitate for 48 hours
      showed an increased basal and a decreased glucose-stimulated insulin secretion (P
      < 0.01). The mRNA level of UCP-2 was increased by 3.7 fold in the 0.5 mmol/L
      concentration of palmitate. When islets were cultured with palmitate (0.5 mmol/L)
      in the presence of rosiglitazone (1.0 micromol/L), both basal and glucose
      stimulated insulin secretion reversed to a pattern of control islets (P < 0.05, P
      < 0.01). The addition of rosiglitazone in the culture medium decreased the mRNA
      level of UCP-2 by 2.2 fold, having a statistically significant difference (P <
      0.05) as compared with islets cultured with palmitate alone. The cell viability
      was not affected. CONCLUSION: The protective effects of rosiglitazone on insulin
      secretion of isolated pancreatic islets under chronic exposure to palmitate might
      be mediated through the downregulation of UCP-2 expression.

PMID- 16620700
TI  - Dexamethasone-induced adipogenesis in primary marrow stromal cell cultures:
      mechanism of steroid-induced osteonecrosis.
AB  - BACKGROUND: In steroid-induced osteonecrosis, hypertrophy and hyperplasia of
      marrow fat cells and lipid deposition of osteocytes can be found in the femoral
      head. However, the precise reason is not clear yet. The aim of this study was to
      observe the effect of dexamethasone (Dex) on differentiation of marrow stromal
      cells (MSCs), and to investigate the pathobiological mechanism of steroid-induced
      osteonecrosis. METHODS: MSCs in cultures were treated with increasing
      concentrations of Dex (0, 10(-9), 10(-8), 10(-7), and 10(-6) mol/L) continuously
      for 21 days. The cells, which were exposed to 0 mol/L (control) or 10(-7) mol/L
      Dex for 4 - 21 days, were then cultured for 21 days without Dex. MSCs were
      stained with Sudan III. Number of adipocytes was counted under a light
      microscope. The activity of alkaline phosphatase (ALP) of MSCs treated with 0,
      10(-8), 10(-7), and 10(-6) mol/L Dex for 12 days, and that treated with 0 mol/L
      and 10(-7) mol/L Dex for 8, 10, or 12 days were determined. The levels of
      triglycerides, osteocalcin and cell proliferation of MSCs treated with 0 mol/L
      and 10(-7) mol/L Dex were detected. The mRNA expression levels of adipose
      specific 422 (aP2) gene and osteogenic gene type I collagen in MSCs treated with
      0 mol/L and 10(-7) mol/L Dex for 6 days were analyzed by whole-cell dot-blot
      hybridization. Statistical analysis was performed using Student's t test and
      analysis of variance. P values less than 0.05 were considered significant
      statistically. RESULTS: The number of adipocytes in cultures increased with the
      duration of MSCs' exposure to Dex and the concentration of Dex. The level of ALP
      activity in the MSCs decreased with concentration of Dex. In the control group,
      it was 8.69 times of that in the 10(-7) mol/L Dex group on day 12 (t = 20.51, P <
      0.001). The level of triglycerides in 10(-7) mol/L Dex group was 3.40 times of
      that in the control (t = 11.00, P < 0.001). The levels of cell proliferation and
      osteocalcin in the control were 1.54 and 2.42 times of that in the 10(-7) mol/L
      Dex group respectively. As compared to the control, the mRNA expression of
      adipose-specific 422 (aP2) gene in 10(-7) mol/L Dex group was significantly
      increased (t = 36.48, P < 0.001), and that of osteogenic gene type I collagen was
      decreased (t = 42.07, P < 0.001). CONCLUSIONS: Dex can directly induce the
      differentiation of MSCs into a large number of adipocytes and inhibit their
      osteogenic differentiation, which provide a novel explanation for the pathologic
      changes of steroid-induced osteonecrosis.

PMID- 16620701
TI  - Brain-derived neurotrophic factor inducing angiogenesis through modulation of
      matrix-degrading proteases.
AB  - BACKGROUND: Recent studies have proved that brain-derived neurotrophic factor
      (BDNF) possesses angiogenic activity in vitro and in vivo. However, the
      proangiogenic mechanism of BDNF has not yet been provided with enough
      information. To explore the proangiogenic mechanism of BDNF, we investigated the
      effects of BDNF on extracellular proteolytic enzymes, including matrix
      metalloproteinases (MMPs) and serine proteases, particularly the urokinase-type
      plasminogen activator (uPA)-plasmin system in human umbilical vein endothelial
      cells (HUVECs) model. METHODS: Tube formation assay was performed in vitro to
      evaluate the effects of BDNF on angiogenesis. The HUVECs were treated with
      various concentrations of BDNF (25 - 400 ng/ml) for different (6 - 48 hours),
      reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assay MMP-2,
      MMP-9, TIMP-1, and TIMP-2 mRNA in HUVECs, and the conditioned medium was analyzed
      for MMP and uPA activity by gelatin zymography and fibrin zymography,
      respectively. uPA, plasminogen activator inhibitor (PAI)-1, tissue inhibitors of
      metalloproteinase (TIMP)-1, and TIMP-2 were quantified by western blotting
      analysis. RESULTS: BDNF elicited robust and elongated angiogeneis in two
      dimensional cultures of HUVECs in comparison with control. The stimulation of
      serum-starved HUVECs with BDNF caused obvious increase in MMP-2 and MMP-9 mRNA
      expression and induced the pro-MMP-2 and pro-MMP-9 activation without significant
      differences in proliferation. However, BDNF had no effect on TIMP-1 and TIMP-2
      production. BDNF increased uPA and PAI-1 production in a dose-dependent manner.
      Maximal activation of uPA and PAI-1 expression in HUVECs was induced by 100 ng/ml
      BDNF, while effects of 200 ng/ml and 400 ng/ml BDNF were slightly reduced in
      comparison with with those of 100 ng/ml. Protease activity for uPA was also
      increased by BDNF in a dose-dependent manner. BDNF also stimulated uPA and PAI-1
      production beyond that in control cultures in a time-dependent manner from 12
      hours to 48 hours after BDNF treatment. CONCLUSIONS: BDNF stimulates MMP and
      uPA/PAI-1 proteolytic network in HUVECs, which may be important to the
      acquisition of proangiogenic potential.

PMID- 16620702
TI  - Comparison of drug-eluting stent and bare-mental stent in the complex small
      vessel intervention.

PMID- 16620703
TI  - Effect of valsartan-eluting stents on the expression of angiotensin II type 2
      receptor.

PMID- 16620704
TI  - Effect of polo-like kinase 1 gene silence on cell cycle and drug resistance in
      K562/A02 cell.

PMID- 16620706
TI  - Treatment of aortic pseudoaneurysm with interventional procedure.

PMID- 16620705
TI  - Outcomes of using Firebird rapamycin eluting stents in routine coronary
      intervention practice: one-year results from the pilot study of Firebird in China
      registry.

PMID- 16620707
TI  - [Several problems of the clinical research for colorectal carcinoma].

PMID- 16620708
TI  - [Impact of STAT6 signaling pathway blockade on apoptosis of human colon cancer
      cells].
AB  - OBJECTIVE: To investigate the relationship between the signal transducer and
      activator of transcription 6 (STAT6) and human colon cancer. METHODS: Four STAT6
      specific recombinant plasmid vectors, pshRNA-STAT6-1, 2, 3, and 4 were
      constructed and transfected into the cultured human colon cancer cells of the
      line HT-29. Seventy-two hours later RT-PCR was used to detect the mRNA expression
      of STAT6 and the apoptosis-related genes Bcl-2 and Bax, flow cytometry (FCM) was
      used to detect the protein expression of phopho-STAT6 (pSTAT6). HT-29 cells were
      inoculated into a plate and transfected with pshRNA-STAT6-1 or pshRNA-STAT6-4,
      and HT-29 cells without transfection were used as controls. Seventy-two hours
      later FCM was used to observe the cell apoptosis. Another HT-29 cells were
      inoculated into a plate and transfected with pshRNA-STAT6-1 or pshRNA-STAT6-4, or
      blank liposome as controls. Seventy-two hours later. Western blotting was used to
      detect the protein expression of Bcl-2 and Bax genes. RESULTS: The p-STAT6
      protein expression rate was 3.2% +/- 0.6% in the pshRNA-STAT6-1 group,
      significantly lower than that of the blank control group (18.2% +/- 0.9%, P <
      0.01) with an inhibition rate of 82.4%, and was 7.9% +/- 0.4% in the pshRNA-STAT6
      4 group, significantly lower than that in the blank control group too (P < 0.01)
      with an inhibition rate of 56.6%. And the p-STAT6 protein expression rates of the
      pshRNA-STAT6-2 and pshRNA-STAT6-3 groups were 16.6% +/- 0.5% and 17.1% +/- 0.7%
      respectively, both not significant different from that of the blank control group
      (both P > 0.05). The early cell apoptosis rates of the pshRNA-STAT6-1 and pshRNA
      STAT6-4 groups were 13.0% and 8.8% respectively, both significantly higher than
      that of the blank control group (0.4%, both P < 0.05). The mRNA expression of Bcl
      2 was significantly lower and the mRNA expression of Bax was significantly higher
      in the pshRNA-STAT6-1 and pshRNA-STAT6-4 groups than in the blank control and
      blank liposome groups (all P < 0.01). The protein expression patterns of Bcl-2
      and Bax was consistent with that of their protein expression. CONCLUSION: STAT6
      signaling pathway inhibits the apoptosis of colon cancer cells by regulation of
      the Bcl-2 and Bax genes.

PMID- 16620709
TI  - [The role of NF-E2-related factor 2 in the induction of uridine 5'-diphosphate
      glucuronosyltransferase 1A and its isoforms by epigallocatechin gallate in colon
      cancer cells].
AB  - OBJECTIVE: To investigate the role of human transcription factor NF-E2-related
      factor 2 (Nrf2) in the induction of the gene expression of uridine 5'-diphosphate
      glucuronosyltransferase (UGT) 1A and its isoforms by epigallocatechin gallate
      (EGCG). METHODS: (1) Human colon carcinoma cells Caco-2 and HT-29 were cultured.
      Immunocytochemistry, western blotting and confocal laser microscopy were used to
      detect the protein expression of Nrf2. Twenty samples of colon carcinoma with
      surrounding normal tissues were collected during endoscopic course. (2) RNA
      interference expression vector pSilencer 3.1-H1 was used to construct four Nrf2
      trageting plasmids: pSilence-Nrf2-A, B, C, and D and a control pSilence-CON.
      Cells were transfected with pSilence-Nrf2 for 48 hours to observe the effects of
      transient transfection. Cells were stably transfected with pSilence-Nrf2-B for 4
      weeks and re-named as Caco-2-siNrf2 and HT-29-siNrf2 (siNrf2 cells), and others
      stably transfected with blank plasmid pSilencer 3.1-H1 were used as controls. (3)
      EGCG was added into the culture fluid of cells before and after the stably
      transfection. RT-PCR was used to detect the mRNA expression of Nrf2, UGT1A,
      UGT1A8 and UGT1A10 in cells and the samples of human colon cancer tissue.
      RESULTS: (1) The expressions of UGT1A8 and UGT1A10 mRNA were significantly lower
      than that in the surrounding healthy mucosa. (2) The mRNA expression of Nrf2,
      UGT1A8, and UGT1A10 increased by 1.8-9.2 times after the addition of EGCG (all P
      < 0.05). Immunocytochemistry, western blotting and immunofluorescence
      demonstrated a significant increase of Nrf2 protein expression in the nucleus
      after treatment with EGCG. (3) SalIenzyme digestion and DNA sequencing confirmed
      that pSilence-Nrf2-A, B, C, and D and pSilence-CON were all successfully
      constructed. The inhibition rate of Nrf2 gene expression was above 80% 48 h after
      transfection with pSilence-Nrf2-B, and that was no significant difference after
      transfection with pSilence-CON (P > 0.05). There was specific inhibition of Nrf2
      in Caco-2-siNrf2, HT-29-siNrf2 cells (both P < 0.01). (4) The basal levels of
      UGT1A8 and UGT1A10 mRNA expression in the Caco-2-siNrf2 and HT-29-siNrf2 cells
      were lower by 15%-65% in comparison with those in control, and the induction of
      genes by EGCG was largely attenuated in them (all P > 0.05). CONCLUSION: Nrf2 is
      localized in the cytoplasm of non-stimulated cells, and EGCG triggered its rapid
      nuclear accumulation. Suppression of Nrf2 gene expression results in down
      regulation of the constructive expression of UGT genes and their induction by
      EGCG. EGCG induces the expression of UGT1A, UGT1A8 and UGT1A10 genes via a Nrf2
      dependent mechanism.

PMID- 16620710
TI  - [Preoperative hepatic and regional arterial infusion chemotherapy in the
      prevention of liver metastasis after colorectal cancer surgery].
AB  - OBJECTIVE: To investigate the effects of preoperative hepatic and regional
      arterial infusion chemotherapy (PHRAIC) in the prevention of liver metastasis of
      colorectal cancer after surgery. METHODS: 110 patients of colorectal cancer
      underwent perfusion of 3 anti-tumor drugs into the hepatic artery and nutrient
      artery of the tumor respectively, radical surgery of the colorectal cancer 7 days
      after, and then general venous chemotherapy 3 weeks after operation, 112 patients
      underwent radical surgery of the colorectal cancer and general venous
      chemotherapy 3 weeks after operation. Follow-up was carried out every month with
      a follow-up period of 34 months +/- 3 months. RESULTS: There were no significant
      difference in post-operational complications between these 2 groups. The 3-year
      liver metastasis rate, 3-year tumor-free survival rate, overall survival rate,
      and median survival time of the stage III patients in the PHRAIC group were
      12.7%, 82.3%, 87.7%, and 40 months +/- 5 months, all significantly better than
      those in the control group (28.3%, 58.7%, 75.5%, and 36 months +/- 3 months
      respectively, P < 0.05 or P < 0.01). CONCLUSION: PHRAIC reduces the liver
      metastasis of colorectal cancer after radical surgery and improves the survival
      of the stage III patients.

PMID- 16620711
TI  - [Effects of p53 inhibitor-alpha on the proliferation and apoptosis in large
      intestinal epithelial cells damaged by hyperthermic chemotherapy].
AB  - OBJECTIVE: To investigate the effects of p-fifty three inhibitor-alpha (PFT
      alpha), a p53 inhibitor, on the proliferation and apoptosis of colon epithelial
      cells damaged by hyperthermic chemotherapy. METHODS: Normal epithelial cells were
      obtained from the mucosa at least 10 cm away from the cancer tissue in a specimen
      of large intestine cancer resected during operation and cultured. PFT-alpha at
      different concentrations was added into the culture fluid to observe its effects
      on the proliferation of the epithelial cells. Epithelial cell in logarithmic
      growth phase were inoculated in 6-well plate and divided into 3 groups: normal
      control (CON) group; hyperthermic chemotherapy (HTC) group, undergoing treatment
      of cisplatin and bath in water at 43 degrees C; and PFT-alpha + HTC group,
      undergoing treatment of PFT-alpha at different concentrations, cisplatin, and
      warm water bath. The cell apoptosis was observed by annexin V-fluorescein
      isothiocyanate/propidium iodide (PI) staining and flow cytometry (FCT). The cell
      cycle was observed by PI staining and FCT. Western blotting was used to detect
      the protein expression of cyclinB1 and Cdc2, and RT-PCR was used to detect the
      mRNA expression of cyclinB1. RESULTS: PFT-alpha at the concentration > 60
      micromol/L significantly inhibited the proliferation of the large intestine
      epithelial cells. The natural apoptosis rate of the large intestine epithelial
      cells (CON group) was 2.9% +/- 0.4%, the apoptosis rate was 27.0% +/- 2.1% in the
      HTC group, and the apoptosis rates of the PFT-alpha + HTC group were 14.8% +/-
      1.5%, 9.7% +/- 1.2%, 6.1% +/- 1.3%, and 3.8% +/- 0.3%, on a downward trend,
      corresponding to the increase of PFT-alpha concentration from 0, 20, 30, to 40
      micromol/L (all P < 0.05). The G(0)/G(1) phase rate of epithelial cells was
      higher and the S phase rate was lower significantly in the PFT-alpha + HTC group.
      The G(2)/M phase rate was higher since the PFT-alpha concentration reached 10
      micromol/L and then increased along with the increase of the PFT-alpha
      concentration; the S phase rates of the PFT-alpha + HTC group with different PFT
      alpha concentrations were all significantly higher than that of the HTC group
      (all P < 0.01), however, were still lower than that of the CON group (all P <
      0.01). The protein expressions of cyclinB1 and Cdc2 in the PFT-alpha + HTC group
      were both significantly higher than those in the CON and HTC groups (all P <
      0.01), without a significant difference between the latter 2 groups. The mRNA
      expression of cyclinB1 in the PFT-alpha + HTC group increased along with the
      increase of the PFT-alpha concentration, and there wee significant differences in
      the mRNA expression of cyclinB1 between the CON and PFT groups and PFT-alpha +
      HTC group with the PFT-alpha concentration > or = 10 micromol/L (P < 0.05 or P <
      0.01). CONCLUSION: PFT-alpha dose-dependently protects the hyperthermic
      chemotherapy-induced damage to the large intestine epithelial cells via
      upregulation of protein and mRNA expression of cyclinB1, increasing the
      phosphorylation level of Cdc2, decreasing the cyclinB1/Cdc2 activity, and
      increasing the G(2)/M phase rate of the cells.

PMID- 16620712
TI  - [Regional denervation after myocardial infarction and its effect on ventricular
      repolarization].
AB  - OBJECTIVE: To investigate whether myocardial infarction (MI) causes heterogeneity
      of sympathetic innervation and to evaluate the effects of sympathetic stimulation
      on myocardial repolarization in the regions of denervation after MI. METHODS:
      Fourteen dogs were randomly divided into 2 equal groups: MI Group, undergoing
      ligation of the left anterior descending coronary artery, and Control Group,
      undergoing sham operation. Four weeks later thoracotomy was performed for the
      second time, the effective refractory period (ERP) of the non-infarcted
      myocardium at the base of heart proximal to the infarcted myocardium and the ERP
      of the non-infarcted myocardium at the cardiac apex distal to the infarcted
      myocardium by S(1)S(2) programmed stimulation. Then the left satellite ganglion
      was exposed, ligated, cut, and stimulated at the proximal end, and ERP was
      determined at the above mentioned regions again. After the ERP measurement the
      heart was taken out to undergo immunohistochemistry to observe the distribution
      of tyrosine hydroxylase (TH) positive nerve fibers. RESULTS: The ERP of the non
      infarcted myocardium at the base of heart proximal to the infarcted myocardium
      was not significantly different from that of the non-infarcted myocardium at the
      cardiac apex distal to the infarcted myocardium before sympathetic stimulation in
      both groups. In MI Group, however, the ERP of the non-infarcted myocardium at the
      base of heart proximal to the infarcted myocardium was significantly shortened
      after stimulation at the satellite ganglion (141 ms +/- 10 ms) in comparison with
      that before the stimulation (162 ms +/- 9 ms, P < 0.01); and the ERP of the non
      infarcted myocardium at the cardiac apex distal to the infarcted myocardium after
      sympathetic stimulation (157 ms +/- 8 ms) was not significantly different from
      that before sympathetic stimulation (161 ms +/- 6 ms), however, was significantly
      longer than that of the non-infarcted myocardium at the base of heart proximal to
      the infarcted myocardium (P < 0.05). In Control Group the ERP values of both the
      basal and apical regions were significantly shorter than those before stimulation
      at the same region (both P < 0.01), however, there were no significant
      differences in the ERP values at the same region before and after the stimulation
      for the 2 regions. Immunohistochemistry showed that TH positive nerve fibers were
      distributed in the whole heart of Control Group and in the heart base of MI
      Group, and no TH positive nerve fiber was seen in the cardiac apex of MI Group.
      CONCLUSION: Regional denervation occurs after MI; Spatial variation of regional
      sympathetic innervation leads to heterogeneity in cardiac repolarization after
      sympathetic stimulation.

PMID- 16620714
TI  - [Relationship between myocyte proliferation and cardiac function in adult rats
      with heart failure].
AB  - OBJECTIVE: To confirm whether there is myocytes proliferation in the adult rat
      with heart failure or not, and to investigate the relationship between myocyte
      proliferation and heart function. METHODS: Descending anterior branch of left
      coronary artery was ligated in 20 adult male SD rats so as to establish an heart
      failure models. Eight rats were used as controls. Hemodynamic parameters, blood
      pressure (BP), left ventricle end systolic pressure (LVESP), left ventricle end
      diastolic pressure (LVEDP), +LVdp/dt(max), and -LVdp/dt(max), were measured 30
      days after the coronary occlusion. Based on the results of heart function
      examination, the heart infarct rats were divided into 2 subgroups: cardiac
      functional compensation subgroup (8 rats), and cardiac functional decompensation
      subgroup (6 rats). Then the rats were killed and their hearts were taken out and
      stained with propidium iodide (PI) and antibody to alpha-sarcomeric actin.
      Immunohistochemistry was used to detect the proliferation cell nuclear antigen
      (PCNA). Confocal microscopy was used to observe the mitotic image. Light
      microscopy was used to observe the PCNA positive rate in the myocardium. RESULTS:
      (1) Mitotic images of myocytes could be identified by confocal microscopy in the
      left ventricle of all rats. (2) PCNA expression was detected in the nuclei of
      both infarct and normal hearts. The PCNA positive rate of the cardiac functional
      compensation subgroup was 7.2% +/- 1.4%, significantly higher than that of the
      control group (2.2% +/- 0.8%, P = 0.648). However, the PCNA positive rate of the
      cardiac functional decompensation subgroup was 3.0% +/- 1.3%, not significantly
      different from that of the control group (P = 0.648). (3) The correlation
      coefficient between PCNA-positivity of cardiomyocytes and +LVdp/dt(max) in the
      infarct rats were 0.80 (P < 0.01) and the correlation coefficient between PCNA
      positivity of cardiomyocytes and -LVdp/dt(max) was -0.76 (P = 0.01). CONCLUSION:
      (1) There is myocyte proliferation in the adult rat heart. (2) Myocyte
      proliferation is positively correlated with heart systolic function, and
      negatively correlated with heart diastolic function in chronic heart failure.

PMID- 16620715
TI  - [Construction of a plasmid vector of fused protein genes driven by human insulin
      like growth factor II P3 promoter].
AB  - OBJECTIVE: To construct a shuttle plasmid vector of fused herpes simplex virus
      thymidine kinase (HSV-tk) gene and enhanced green fluorescent protein (EGFP) gene
      driven by human insulin-like growth factor II (IGF-II) P3 promoter, and
      investigate the special killing effect of the HSV-tk/ganciclovir (GCV) system on
      hepatocellular carcinoma (HCC) cells. METHODS: An adenovirus shuttle plasmid,
      pDC316-tkEGFP-CMV containing fused genes tkEGFP and an adenovirus shuttle plasmid
      pDC316-tkEGFP-P3 driven by IGF-II P3 promoter were constructed by techniques of
      gene recombination and screening, and identified by restriction digestion and
      sequencing analysis. Human hepatocellular carcinoma cells HepG2 and human
      cervical carcinoma cells HeLa were cultured and transfected with these 2
      recombinant shuttle plasmids. RT-PCR was used to detect the mRNA expression of
      EGFP and HSV/tk. GCV of the final concentrations of 0, 1, 10, and 100 microg/ml
      respectively was added into the culture fluid of the HepG2 cells transfected with
      pDC316-tkEGFP-CMV or pDC316-tkEGFP-P3, and MTT method was used to detect the cell
      inhibition rate. RESULTS: Digestion and sequencing analysis showed that the
      recombinant plasmid pDC316-tkEGFP-P3 accorded with the design. Fluorescent
      microscopy showed that EGFP was expressed only in the HepG2 cells, but not in the
      HeLa cells. RT-PCR showed that mRNA expression of EGFP and HSV/tk could be seen
      in both HepG2 and HeLa cells transfected with pDC316-tkEGFP-CMV or pDC316-tkEGFP
      P3, however, only in the pDC316-tkEGFP-P3 transfected HepG2 cells, but not in the
      HeLa cells transfected with pDC316-tkEGFP-P3. MTT assay showed that GCV dose
      dependently inhibited the 2 cancer cells, the inhibition rates of GCV of the
      final concentrations of 1, 10, and 100 microg/ml were 24.1% +/- 1.9%, 45.1% +/-
      1.7%, and 69.4% +/- 3.6% in the HepG2 cells, and 25.1% +/- 1.6%, 49.3% +/- 1.1%,
      and 72.2% +/- 2.9% in the HeLa cells. However, the inhibition rates of the pDC316
      tkEGFP-P3-transfected HepG2 cells by GCV of the final concentrations of 1, 10,
      and 100 microg/ml wee 19.8% +/- 1.3%, 36.2% +/- 2.0% and 48.7% +/- 1.9%
      respectively, all significantly lower than those of the pDC316-tkEGFP-CMV
      transfected HepG2 cells (all P < 0.01), and no significant cell inhibition was
      found in the HeLa cells transfected with pDC316-tkEGFP-CMV. CONCLUSION: A shuttle
      plasmid vector containing the tkEGFP fusion protein gene driven by IGF-II P3
      promoter has been constructed successfully and its specific expression in HepG2
      cells provides a sound basis for targeted gene therapy for HCC.

PMID- 16620716
TI  - [Effects of ciclosporin and tacrolimus on replication of hepatitis B virus in
      vitro: a comparative study].
AB  - OBJECTIVE: To investigate the effects of ciclosporin (CsA) and tacrolimus (FK506)
      on replication of hepatitis B virus (HBV) in vitro. METHODS: HBV genome
      permanently transfected human liver cancer cells of the line HepG2.2.15 were
      cultured. CsA and FK506 at different concentrations were added into the culture
      fluid so as to identify the nontoxic concentrations by MTT method. Then the
      HepG2.2.15 cells were treated by CsA and FK506 at different nontoxic
      concentrations respectively for 4 days. ELISA was used to detect the HB surface
      antigen (HBsAg) and HB e antigen (HBeAg) in the supernatant. The relative
      replication level of HBV DNA was detected by slot blot analysis. RESULTS: MTT
      method confirmed that the nontoxic concentrations of CsA and FK506 were 0-40.0
      microg/ml and 0-400 ng/ml respectively. After the treatment of CsA at the
      concentration of 1.3, 2.5, and 5.0 microg/ml, in comparison to the control group,
      the suppression rates of HBsAg expression in the HepG2.2.15 cells were 16.5% +/-
      9.4%, 21.5% +/- 8.9%, and 33.1% +/- 5.3% respectively (all P < 0.05); the
      suppression rates of HBeAg expression in the HepG2.2.15 cells were 7.8% +/- 2.2%,
      11.0% +/- 2.3%, and 20.8% +/- 1.5% respectively (all P < 0.05); and the HBV DNA
      replication levels were 56 +/- 16, 42 +/- 11, and 40 +/- 10 respectively (P >
      0.05, P < 0.05, and P > 0.05). However, FK506 at different nontoxic
      concentrations showed no significant inhibitory effect on the levels of HBsAg,
      HBeAg, and HBV DNA. CONCLUSION: CsA dose-dependently inhibits the HBV replication
      in vitro, and FK506 does not exercise similar effects.

PMID- 16620718
TI  - [Application of contrast-enhanced ultrasound to increase the diagnostic rate of
      liver tumor by biopsy].
AB  - OBJECTIVE: To evaluate the clinical utility of contrast-enhanced ultrasound
      (CEUS) in percutaneous liver biopsy of focal liver lesions. METHODS: Two hundred
      and eleven patients with unidentified space occupying lesions in liver, 112 males
      and 74 females, aged 52 (16-78), were randomly divided into 2 groups: CEUS group
      in which 96 cases with 149 lesions underwent liver biopsy with 21-18 gauge
      needles directed by real time grey CEUS, and routine ultrasound (US) group in
      which 115 patients with 153 lesions underwent biopsy guided by conventional
      ultrasonography. There was no significant difference in the size of lesions
      between these 2 groups. There were 75 minute malignant lesions with the size of <
      or = 2.0 cm (24.8%) in 67 patients, 12.9% in the CEUS group and 11.9% in the US
      group. Obtainment of adequate specimen for pathological examination meant
      successful biopsy. Definite diagnosis was made by the combination of the results
      of pathological examination, CEUS, CT, MRI, angiography, serum alpha-fetoprotein,
      and 3 to 6-month follow-up. RESULTS: The proportion of no more than 2 puncture
      attempts in the CEUS group was 33/19, significantly higher than that in the US
      group (8/153, P = 0.0007). The biopsy success rate of the CEUS group was 98.7%,
      significantly higher than that of the US group (91.5%, P = 0.0096). The accurate
      diagnosis rate of the CEUS group was 96.0%, significantly higher than that of the
      US group (87.6%, P = 0.0165). The accurate diagnosis rate of malignant lesions
      with the size of < or = 2.0 cm in the CEUS group was 97.4%, significantly higher
      than that in the US group (80.6%, P = 0.0473). Among the 112 confirmed malignant
      lesions in the US group 15 had been diagnosed as benign by pathological
      examination of the biopsy specimens with a false negative rate of 13.4%. The
      relevant patients underwent CEUS-guided biopsy again and 14 of the 15 lesions
      were confirmed as malignant finally and the size of 6 of the 14 lesions was < or
      = 2.0 cm. Except for one case of pneumothorax in the US group no major
      complication occurred. CONCLUSION: Biopsy guided by CEUS is more accurate in
      location and diagnosis of malignant lesions and minute tumors in the liver, thus
      increasing the success rate of biopsy and the confirmed diagnosis rate of
      malignant lesions.

PMID- 16620721
TI  - [Novel double heterozygous mutations on Met306Val and Thr181Asn related to a
      hereditary coagulation factor VII deficiency].
AB  - OBJECTIVE: To identify the genetic defect of coagulation factor VII in a Chinese
      family with hereditary FVII deficiency. METHODS: Peripheral blood samples were
      collected from the proband of hereditary FVII deficiency, female, aged 15, 4
      members of her family, and 100 healthy persons. Genomic DNA was isolated. All the
      exons and exon-intron boundaries of FVII gene were amplified by PCR, then the PCR
      products were sequenced by direct sequencing. Restrictive endonuclease analysis
      was performed in all of the family members and the 100 healthy donors to exclude
      gene polymorphism. Biostructural analysis of the mutated FVII was completed by
      molecular modeling. RESULTS: Double heterozygous mutations in the proband were
      identified: A-->G mutation at position 10833 and C-->A mutation at position 9643,
      resulting in Met306Val and Thr181Asn substitution respectively. Heterozygosity
      for Met306Val was confirmed in the proband's mother and her elder sister;
      heterozygosity for Thr181Asn was confirmed in the proband's father. It was found
      by computer simulated molecular model that the Met306Val replacement, which was
      located on the surface of the FVII molecule, might cause steric hindrance and
      change the configuration and function of FVII protein. CONCLUSION: Double
      heterozygous mutations for Met306Val and Thr181Asn in FVII gene have been found
      in a proband with hereditary FVII deficiency. The Met306Val substitution in FVII
      gene is a novel mutation in hereditary FVII deficiency. The heterozygous mutation
      of FVII gene may change the configuration of FVII protein and result in FVII
      dysfunction.

PMID- 16620720
TI  - [Effects of amiodarone versus sotalol in treatment of atrial fibrillation: a
      random controlled clinical study].
AB  - OBJECTIVE: To evaluate the effects and adverse reactions of amiodarone and
      sotalol in treatment of atrial fibrillation. METHODS: One hundred and two
      patients with atrial fibrillation, 56 males and 46 females, aged 56 +/- 11, were
      randomized into 2 equal groups: amiodarone group, taking amiodarone 600 mg/d for
      7 days, 400 mg/d for 7 days, 200 mg/d for 7 days, and then 200 mg/d as
      maintenance dosage if conversion to sinus rhythm occurred; and sotalol group,
      taking sotalol 40-80 mg/d for one week, 160 mg/d for 2 weeks and then 40-80 mg/d
      as maintenance dosage if conversion to sinus rhythm occurred. If the cardiac
      rhythm failed to be converted to sinus rhythm after three week the medication was
      stopped. All the patients were followed up for 12-24 months and therapeutic
      effects were evaluated by echocardiography, electrocardiogram and Holter monitor.
      RESULTS: (1) Conversion to sinus rhythm occurred in 40 patients in the amiodarone
      group with an effective rate of 78.4%, and in 36 patients in the sotalol group
      with an effective rate of 70.6%. (2) Conversion to sinus rhythm occurred in the
      first week in 34 patients of the amiodarone group and in 10 patients of the
      sotalol group. (3) 67.5% of the patients with conversion to sinus rhythm in the
      amiodarone group and 41.7% of the patients with conversion to sinus rhythm in the
      sotalol group maintained sinus rhythm in the following 12 months; and 44.4%
      patients with conversion to sinus rhythm in the amiodarone group and 26.7% of the
      patients with conversion to sinus rhythm in the following 24 months. (4) 10
      patients in the sotalol group taking a maintenance dosage of 80 mg/d showed
      atrial ventricular block and severe bradycardia during the follow-up of 6-2
      months, then the medication was stopped, but there was no severe arrhythmia in
      amiodarone group. (5) It was difficult to maintain sinus rhythm when atrial
      fibrillation lasting longer than 12 months was a predictive factor of failure to
      maintain sinus rhythm. CONCLUSION: There is no significant difference between
      amiodarone and sotalol in converting atrial fibrillation to sinus rhythm.
      However, amiodarone is more effective in maintenance of sinus rhythm than
      sotalol. The adverse reaction of amiodarone on heart is less severe than that of
      sotalol.

PMID- 16620722
TI  - [Research of RhD protein in Rh blood group Del phenotype].
AB  - OBJECTIVE: To study the expression of RhD protein in Rh blood group Del
      phenotype. METHODS: Peripheral blood samples were collected from 3 voluntary
      blood donors with different Rh phenotypes: CCD(el)D(el)ee, CcD(el)dee, and
      CcD(el)D(el)ee, and 4 controls: 2 RhD positive with the phenotypes of CCDDee and
      CcDDEe, and 2 RhD negative with the phenotypes: Ccddee and ccddee. Reverse
      transcriptase PCR (RT-PCR) and cDNA sequencing were used to detect the RhD mRNA
      and the expression of Del protein. RESULTS: The Del individuals all showed
      complicated RhD mRNA isolations, including 6 transcripts: isoforms with exons 7-9
      spliced, exons 7 and 9 spliced, exons 8 and 9 spliced, exon 9 spliced and 2 long
      transcripts with exons 8 and 9 spliced or exon 9 spliced, but containing an
      additional segment of sequence from RHD intron 7 (917-1086, GenBank AB035194),
      those transcripts all being out of exon 9 and the Del9 transcript being the most
      similar to the normal RhD mRNA. CONCLUSION: Normal RhD mRNA does not exist in the
      Del blood group that does not code normal RhD protein.

PMID- 16620729
TI  - [Therapy with antipsychotic drugs as a risk factor for diabetes in schizophrenia:
      a case-control study].
AB  - BACKGROUND AND OBJECTIVES: Atypical antipsychotics have been related with
      hyperglycaemia, diabetes mellitus, weight gain and lipid alterations in some
      patients. This study analyzed whether continuous treatment with risperidone,
      olanzapine, or clozapine entails a risk of glucose or lipid metabolism
      alterations in schizophrenic patients. PATIENTS AND METHOD: Patients included in
      this study were schizophrenics who had received mono-therapeutic with clozapine,
      olanzapine or risperidone for a period of 1 to 3 years. Those schizophrenic
      patients who were diagnosed as diabetic during psychiatric treatment and those
      who showed fasting glycemia greater than or equal to 126 mg/dl in two consecutive
      measurements were considered cases. The remaining schizophrenic patients who were
      receiving treatment and did not show these alterations were considered controls.
      RESULTS: In the adjusted analysis (multivariate logistic regression) of the
      effect of antipsychotic treatment on the presence of diabetes, which also
      assessed age and body-mass index, the adjusted odds ratio (OR) for olanzapine
      relative to risperidone was 2.22 (95% confidence interval [CI], 1.12-4.22), (p =
      0.0228); and that for clozapine relative to risperidone was 2.87 (95% CI, 1.19,
      6.93), (p = 0.0192). Both results reveal a significantly greater risk for the
      appearance of diabetes mellitus in patients treated with olanzapine or clozapine
      than in those treated with risperidone. There were significant differences in the
      risk of increase in triglycerides in patients receiving olanzapine (OR = 1.34; p
      = 0.0075) and clozapine (OR = 1.58; p = 0.0028). CONCLUSIONS: The risk of the
      appearance of diabetes mellitus in patients treated with olanzapine is twice as
      high as that in patients treated with risperidone, and the risk in patients
      treated with clozapine is nearly triple as high as that found in patients treated
      with risperidone. Risperidone appears to be a safer antipsychotic drug in the
      long term, with regard to the risk of alterations in glucose and lipid
      metabolism.

PMID- 16620730
TI  - [Prevalence of mental disorders and associated factors: results from the ESEMeD
      Spain study].
AB  - BACKGROUND AND OBJECTIVE: The ESEMeD-Spain project is an epidemiological study
      about mental disorders in Spain. We present 12 month-prevalence and lifetime
      prevalence of the main mood, anxiety and alcohol use disorders; the influence of
      sociodemographic factors on its presence and age of onset of the disorders.
      SUBJECTS AND METHOD: Cross-sectional household survey of a representative sample
      of the population of Spain 18 years or older. Sample size was 5.473 individuals.
      The WHO World Mental Health Survey Initiative version of the Composite
      International Diagnostic Interview (WMH-CIDI) was used. Response rate was 78.6%.
      Results have been weighted to represent the population of Spain. RESULTS: 19.5%
      of the individuals presented a mental disorder sometime in their lifetime
      (lifetime-prevalence) and 8.4% in the last 12 months (12 month-prevalence). The
      most frequent mental disorder was major depressive episode, with a 12-month
      prevalence of 3.9% and a lifetime-prevalence of 10.5%. The other most lifetime
      prevalent disorders were specific phobia, alcohol abuse disorder, and dysthymia.
      Factors associated to presenting a mental disorder were being female, being
      separated, divorced or widowed, and being unemployed, on sick leave or
      incapacitated. Social phobia, agoraphobia and specific phobia appear at younger
      ages, while mood disorders and panic disorder appears later in life. CONCLUSIONS:
      The ESEMeD-Spain study can provide careful outcomes to understand the impact of
      mental disorders in Spain.

PMID- 16620731
TI  - [Promoter hypermethylation status of the mismatch repair gene hMLH1 in patients
      with sporadic renal cell carcinoma].
AB  - BACKGROUND AND OBJECTIVE: Epigenetic inactivation is a gene function abnormality
      that produces no changes in the DNA sequence, with the most frequent epigenetic
      alteration being hypermethylation of CpG islands in the promoter regions of the
      genes. Based on recent indications of a potential relationship between mismatch
      repair genes and renal cell carcinoma (RCC), we were interested in investigating
      the existence of promoter hypermethylation of the hMLH1 gene in tumor DNA samples
      from patients with sporadic RCC. MATERIAL AND METHOD: Sixty-five tumor tissue
      specimens were collected consecutively. The DNA was first obtained and purified,
      then digested with the restriction enzymes Hpa II and Msp I, followed by
      polimerase chain reaction amplification of 3 promoter regions of the hMLH1 gene,
      agarose gel electrophoresis, and densitometric analysis of the images of the
      amplified bands. RESULTS: Mean patient age was 63.7 years. The most frequent cell
      type was clear cell carcinoma (67.7%). 73.9% of tumors were diagnosed in stages
      below pT2, 9.3% had gland involvement and 20%, distant metastasis. No somatic
      hypermethylation was detected in the promoter region of the hMLH1 gene in any of
      the patients studied. CONCLUSIONS: Our data indicate that promoter
      hypermethylation of the hMLH1 gene is not implicated in the pathogenesis of
      sporadic RCC, and therefore the existence of another type of mutation,
      microsatellite instability and/or loss of heterozygosity should be examined to
      determine the possible role of this gene in sporadic RCC.

PMID- 16620732
TI  - [Genetic methylation in carcinogenesis and its application in clinical oncology].

PMID- 16620733
TI  - [Deletions of the mitochondrial DNA associated to chronic progressive external
      ophthalmoplegia with ragged-red fibers in 2 Brazilian patients].
AB  - BACKGROUND AND OBJECTIVE: Our purpose was to report the neurological
      manifestations and molecular-genetic analysis of mitochondrial DNA associated
      with chronic progressive external ophthalmoplegia (CPEO) and raged red fibers
      (RRFs). PATIENTS AND METHOD: Two patients, a male and a female (32 and 28 year
      old, respectively), were studied due to progressive palpebral ptosis associated
      with RRFs in muscle biopsy. Both patients were subjected to neurological,
      histochemical and enzymatic analysis of muscular biopsy, analysis of cerebro
      spinal fluid, and molecular analysis of mitochondrial DNA. RESULTS: Symptoms
      started at ages 24 and 17 years. Initial symptoms were palpebral ptosis,
      progressive limitation of vertical and horizontal gaze, fatigue and exercise
      intolerance, and weakness of proximal muscles. Brain MRIs were normal in both
      patients. Both patients had deletions of muscle mitochondrial DNA with similar
      size (5,425 and 5,112 base pairs) and location. CONCLUSIONS: CPEO with RRFs is
      usually associated with huge deletions in mitochondrial DNA. Fatigue and proximal
      muscle weakness can be found during the follow-up.

PMID- 16620734
TI  - [The International Classification of Functioning, Disability and Health:
      applicability and usefulness in clinical practice].

PMID- 16620735
TI  - [Prophylactic treatment of migraine].

PMID- 16620736
TI  - [Importance of clinic documentation for the justice administration].

PMID- 16620737
TI  - [Bibliometric analysis of rare diseases in Spain: need for adaptation of the
      methodology to the objective].

PMID- 16620738
TI  - [Pulmonary cryptococcosis in an immunocompetent patient].

PMID- 16620739
TI  - The effect on teen driving outcomes of the Checkpoints Program in a state-wide
      trial.
AB  - Crash rates among teenagers are highly elevated during the first months of
      licensure. Parent-imposed driving restrictions on initial driving privileges can
      reduce exposure to high-risk driving conditions, thus reducing crash risk while
      teens' driving proficiency develops. This report describes the effect of the
      Checkpoints Program on driving limits and outcomes. Connecticut teens who
      obtained a learners permit over a 9-month period were recruited, providing a
      final sample of 3743 who obtained driver licenses. Families were randomized to
      the intervention or comparison condition. Intervention families received by mail
      a series of persuasive communications related to high-risk teen driving and a
      parent-teen driving agreement, while comparison families received on the same
      schedule general information on driving and vehicle maintenance. Relative to the
      comparison group, teens and parents in the Checkpoints Program reported
      significantly greater limits on high-risk teen driving conditions at licensure, 3
      , and 6-months post-licensure; and intervention teens reported significantly less
      risky driving at each reporting period. By the 12-month follow up teens in the
      intervention group were significantly less likely than those in the comparison
      group to have had a traffic violation. However, no treatment group effect was
      found for crashes. This is the first study to report significant effects on teen
      driving behavior and performance of education designed to increase parental
      imposed teen driving limits.

PMID- 16620740
TI  - Driver experience and cognitive workload in different traffic environments.
AB  - How do levels of cognitive workload differ between experienced and inexperienced
      drivers? In this study we explored cognitive workload and driver experience,
      using a secondary task method, the peripheral detection task (PDT) in a field
      study. The main results showed a large and statistically significant difference
      in cognitive workload levels between experienced and inexperienced drivers.
      Inexperienced, low mileage drivers had on average approximately 250 milliseconds
      (ms) longer reaction times to a peripheral stimulus, than the experienced
      drivers. It would, therefore, appear that drivers with better training and
      experience were able to automate the driving task more effectively than their
      less experienced counterparts in accordance with theoretical psychological
      models. It has been suggested that increased training and experience may provide
      attention resource savings that can benefit the driver in handling new or
      unexpected traffic situations.

PMID- 16620741
TI  - Patterns of driver stress and coping strategies in a Greek sample and their
      relationship to aberrant behaviors and traffic accidents.
AB  - This paper presents an investigation into the relationship between driver stress,
      coping strategies and aberrant driving of a Greek sample of company employees
      (N=714). The results supported the main factor structures of the Driver Behavior
      Inventory (Matthews, G., Tsuda, A., Xin, G., Ozeki, Y., 1999. Individual
      differences in driver stress vulnerability in a Japanese sample. Ergonomics 42,
      401-415) and Driver Behavior Questionnaire (Kontogiannis, T., Kossiavelou, Z.,
      Marmaras, N., 2002. Self-reports of aberrant behavior on the roads: errors and
      violations in a sample of Greek drivers. Accident Anal. Prev. 34, 391-399). An
      inventory of coping strategies was also examined in terms of self reports.
      Confrontive coping was characteristic of drivers high on aggression who also had
      higher rates of mistakes and violations. Coping in terms of self-criticism was
      exhibited by drivers high on dislike of driving (i.e., anxiety) who reported a
      higher incidence of mistakes. Task-focus coping was characteristic of alertness
      and had a weak correlation with confidence. Drivers high in confidence reported
      fewer mistakes and violations which, in association with low perception of risk,
      was a particularly worrying aspect of driving. A contextual model of accident
      involvement was tested with LISREL in which violations yielded a direct effect
      whilst aggression yielded an indirect effect mediated by violations. Alertness
      and confidence were both related to safety orientation but failed to predict
      accident rates and speeding convictions.

PMID- 16620742
TI  - The nature of the syllabic neighbourhood effect in French.
AB  - We investigated whether and how sublexical units such as phonological syllables
      mediate access to the lexicon in French visual word recognition. To do so, two
      lexical decision task (LDT) experiments examined the nature of the syllabic
      neighbourhood effect. In Experiments 1a and b, the number of higher frequency
      syllabic neighbours was manipulated while controlling for the first bigram. The
      results failed to show a pure syllabic neighbourhood effect. In Experiments 2a
      and b, syllabic neighbourhood and bigram frequency were factorially manipulated.
      The interaction showed that the syllabic neighbourhood effect was inhibitory when
      bigram frequency was high, whereas it was facilitatory when bigram frequency was
      low. Similar patterns of results were found in both the yes/no (Experiments 1a
      and 2a) and go/no-go LDTs (Experiments 1b and 2b), so varying task requirements
      of the lexical decision did not influence the effect. These findings are
      discussed in the context of parallel distributed processing and interactive
      activation models, and suggest that orthographic redundancy properties contribute
      to the influence of phonological syllables.

PMID- 16620743
TI  - Role of pfmdr1 mutations on chloroquine resistance in Plasmodium falciparum
      isolates with pfcrt K76T from Papua New Guinea.
AB  - The N86Y mutation in pfmdr1 is reported to play an additional role for the
      chloroquine resistance in Plasmodium falciparum isolates. However, not much has
      been done to clarify whether this mutation augments the level of chloroquine
      resistance in the isolates harboring pfcrt K76T mutation. We compared the in
      vitro chloroquine efficacy between pfcrt K76T mutant parasites with or without
      N86Y mutation from Papua New Guinea. A total of 57 isolates (4% sensitive, 14%
      borderline, and 82% resistant) were successfully tested in vitro for chloroquine
      sensitivity. We found a slightly higher effective concentration of chloroquine
      needed to inhibit P. falciparum by 50% (mean EC50=107 nM) in isolates with the
      pfcrt K76T+pfmdr1 N86Y than that in isolates with the pfcrt K76T+pfmdr1 N86
      (EC50=88 nM), but this difference was not statistically significant. A
      significant non-random association was observed between the pfcrt K76T and pfmdr1
      N86Y alleles. Our results suggest that the pfmdr1 N86Y mutation plays a
      compensatory role to chloroquine-resistant isolates under a chloroquine pressure
      while it may also augment the level of chloroquine resistance in the K76T
      parasites to a small extent.

PMID- 16620744
TI  - Use of Western blotting filtration to detect UV-cross-linked protein: RNA
      complexes.

PMID- 16620745
TI  - Rapid detection of Clostridium botulinum toxins A, B, E, and F in clinical
      samples, selected food matrices, and buffer using paramagnetic bead-based
      electrochemiluminescence detection.
AB  - Sensitive and specific electrochemiluminescence (ECL) assays were used to detect
      Clostridium botulinum neurotoxins serotypes A, B, E, and F in undiluted human
      serum, undiluted human urine, assay buffer, and selected food matrices (whole
      milk, apple juice, ground beef, pastry, and raw eggs). These novel assays used
      paramagnetic bead-based electrochemiluminescent technology in which biotinylated
      serotype-specific antibodies were bound to streptavidin-coated paramagnetic
      beads. The beads acted as the solid support and captured analyte from solution.
      Electrochemiluminescent detection relied on the use of ruthenium chelate-labeled
      anti-serotype antibodies and analysis with a BioVeris M-Series M1R analyzer. The
      sensitivities of the assays in clinically relevant matrices were 50 pg/ml for
      serotypes A and E, 100 pg/ml for serotype B, and 400 pg/ml for serotype F. The
      detection limits in selected food matrices ranged from 50 pg/ml for serotype A to
      50 to 100 pg/ml for serotypes B, E, and F. The antibodies used for capture and
      detection exhibited no cross-reactivity when tested with the other serotypes.
      When purified native toxin was compared with toxins complexed to neurotoxin
      associated proteins, no significant differences in assay response were noted for
      serotypes A, B, and F. Interestingly, the native form of serotype E exhibited
      reduced signal and limit of detection compared with the complexed form of the
      protein. We suspect that this difference may be due to trypsin activation of this
      particular serotype. The assays described in this article demonstrate limits of
      detection similar in range to the gold standard mouse bioassay, but with greatly
      reduced time to data. These rapid sensitive assays may have potential use in
      clinical settings, research studies, and screening of food products for botulinum
      toxins.

PMID- 16620746
TI  - Enzyme-mediated individual nanoparticle release assay.
AB  - Numerous methods have been developed to measure the presence of macromolecular
      species in a sample; however, the number of methods that detect functional
      activity or modulators of that activity is more limited. To address this
      limitation, an approach was developed that uses the optical detection of
      nanoparticles as a measure of enzyme activity. Nanoparticles are increasingly
      being used as biological labels in static binding assays; here, we describe their
      use in a release assay format, where the enzyme-mediated liberation of individual
      nanoparticles from a surface is measured. A double-stranded fragment of DNA is
      used as the initial tether to bind the nanoparticles to a solid surface. The
      nanoparticle spatial distribution and number are determined using dark-field
      optical microscopy and digital image capture. Site-specific cleavage of the DNA
      tether results in nanoparticle release. The methodology and validation of this
      approach for measuring enzyme-mediated, individual DNA cleavage events, rapidly,
      with high specificity, and in real-time are described. This approach was used to
      detect and discriminate between nonmethylated and methylated DNA, and
      demonstrates a novel platform for high-throughput screening of modulators of
      enzyme activity.

PMID- 16620747
TI  - Identification and discrimination of extracellularly active cathepsins B and L in
      high-invasive melanoma cells.
AB  - We established a novel protocol for lithium dodecyl sulfate (LDS) gelatin
      zymography, which operates under reducing conditions and at a slightly acidic pH
      value (6.5). This zymographic assay is based on polyacrylamide gel
      electrophoresis and facilitates the electrophoretic separation of human
      cathepsins in an active state. By this technique, activity of purified human
      liver cathepsin B was detected at a concentration as low as 50 ng and was blocked
      only in the presence of the cysteine protease inhibitor E-64 and the specific
      cathepsin B inhibitor CA-074 but not by aspartate, serine, or matrix
      metalloprotease inhibitors. The method was applied to analyze cathepsin
      activities in cell culture supernatants of the high-invasive melanoma cell line
      MV3. Interestingly, LDS zymography of MV3 cell supernatants in combination with
      specific inhibitors of cathepsins B and L identified three forms of
      extracellularly active cathepsin B and two forms of proteolytically active
      cathepsin L. We herein describe the generation and biochemical significance of
      acidic LDS zymography. This novel method permits not only the enzymatic analysis
      of purified cysteine proteases but also the identification and discrimination of
      different cathepsin activities in biological fluids, cell lysates, or
      supernatants, especially of cathepsins B and L, which are closely linked to major
      inflammatory and malignant processes.

PMID- 16620748
TI  - A cell-penetrating peptide derived from mammalian cell uptake protein of
      Mycobacterium tuberculosis.
AB  - A Mycobacterium tuberculosis membrane protein called Mycobacterium cell entry
      protein (Mce1A) was previously shown to mediate the uptake of nonpathogenic
      Escherichia coli and latex beads by nonphagocytic mammalian cells. Here we
      characterize further the in vitro invasive activity of Mce1A using colloidal gold
      nanoparticles and fluorescent latex microspheres. Mce1A-coated colloidal gold
      particles induced plasma membrane invagination and entered membrane-bound
      compartments inside HeLa cells. Few of the protein-coated particles were also
      found in the cytosol compartment. Cytochalasin D and nocodazole inhibited the
      uptake by HeLa cells, indicating that rearrangement of both microtubules and
      microfilaments was necessary for the uptake. The functional domain of Mce1A for
      invasion was narrowed to a highly basic 22-amino acid sequence termed Inv3. A
      synthetic Inv3 peptide stimulated uptake of colloidal gold particles as well as
      latex microspheres by HeLa cells. A chimeric protein composed of Inv3 sequence at
      the N terminus of beta-galactosidase appeared to stain the nuclear membrane,
      suggesting that it entered the HeLa cell cytoplasm. These observations suggest
      that the cell uptake activity of Mce1A is confined to a small peptide domain
      located in the core region of the protein. Inv3 could be used to ferry any
      protein in fusion with it into mammalian cells and may serve as a potent nonviral
      delivery system.

PMID- 16620750
TI  - Covalent immobilization of histidine-tagged proteins for surface plasmon
      resonance.

PMID- 16620749
TI  - Resonance Rayleigh-scattering method for the determination of proteins with gold
      nanoparticle probe.
AB  - Gold nanoparticles with a 12-nm diameter were used as probes for the
      determination of proteins by resonance Rayleigh-scattering techniques. In weak
      acidic solution, large amounts of citrate anions will self-assemble on the
      surface of positively charged gold nanoparticles to form supermolecular compounds
      with negative charges. Below the isoelectric point, proteins with positive
      charges such as human serum albumin (HSA), bovine serum albumin (BSA), and
      ovalbumin (Ova) can bind gold nanoparticles to form larger volume products (the
      diameter of the binding product of gold nanoparticles with HSA is 23 nm.) through
      electrostatic force, hydrogen bonds, and hydrophobic effects, which can result in
      a red shift of the maximum absorption wavelength, the remarkable enhancement of
      the resonance Rayleigh-scattering intensity (RRS), and the appearance of the RRS
      spectra. At the same time, the second-order-scattering (SOS) and frequency
      doubling-scattering (FDS) intensities are also enhanced. The binding products of
      gold nanoparticles with different proteins have similar spectral characteristics
      and the maximum wavelengths are located near 303 nm for RRS, 540 nm for SOS, and
      390 for FDS, respectively. The scattering enhancement (DeltaI) is directly
      proportional to the concentration of proteins. Among them, the RRS method has the
      highest sensitivity and the detection limits are 0.38 ng/ml for HSA, 0.45 ng/ml
      for BSA, and 0.56 ng/ml for Ova, separately. The methods have good selectivity. A
      new RRS method for the determination of trace proteins using a gold nanoparticle
      probe has been developed. Because gold nanoparticle probes do not need to be
      modified chemically in advance, the method is very simple and fast.

PMID- 16620751
TI  - A light scattering assay for arachidonic acid-induced tau fibrillization without
      interfering micellization.

PMID- 16620752
TI  - Detection of gamma-aminobutyric acid-induced glutamate release in acute mouse
      hippocampal slices with a patch sensor.
AB  - gamma-Aminobutyric acid (GABA)-stimulated release of L-glutamate from various
      neuronal regions of acute mouse hippocampal slices was detected with a patch
      sensor that responds to L-glutamate at the sub-micromolar level. The response of
      the patch sensor to L-glutamate was evaluated in terms of an integrated current.
      The integrated current increased with the concentration of L-glutamate ranging
      from 0.50 to 5.0 microM. By using the patch sensor, GABA-induced L-glutamate
      release from acute mouse hippocampal slices was detected. The effect of
      antagonists for GABA(A) and GABA(B) receptors on the L-glutamate release was also
      investigated. The GABA (25 microM) stimulation induced the release of L-glutamate
      via GABA(A) receptor in the CA1 region, but GABA did not induce L-glutamate
      release in the CA3 region. However, in the presence of the GABA(B) receptor
      antagonist (3-aminopropyl)(diethoxymethyl)phosphinic acid (CGP-35348), release of
      L-glutamate in the CA3 region was evoked by GABA stimulation. The glutamate
      release was completely suppressed when both GABA(A) and GABA(B) receptor were
      inhibited. The current results show that the glutamate release in the CA3 region
      occurs via a GABA(A) pathway when GABA(B) receptors are inhibited.

PMID- 16620753
TI  - Evaluation of saliva as a source of human DNA for population and association
      studies.
AB  - A simple noninvasive procedure for saliva sample collection and DNA extraction
      was developed. On average, the amount of human DNA (as measured by a TaqMan-based
      assay) was about 11.4 microg/mL saliva, which is more than can be obtained from
      other noninvasive samples such as cheek swabs. However, the presence of large
      amounts of nonhuman DNA (up to 90% of the total extracted DNA) in saliva samples
      does necessitate DNA quantitation methods that are specific for human DNA. We
      were able to reliably and accurately type different genetic markers (mDNA
      sequences, Y-chromosomal single-nucleotide polymorphisms, and autosomal
      microsatellite loci) from saliva samples stored for up to 30 days at 37 degrees
      C, making this method well-suited for field conditions and convenient
      transportation of samples back to the laboratory. Thus, saliva can be considered
      a reliable source of DNA for a wide variety of genetic studies.

PMID- 16620754
TI  - Methods for enhancing the accuracy and reproducibility of Congo red and
      thioflavin T assays.

PMID- 16620755
TI  - Polymerase chain reaction of 2-kb cyanobacterial gene and human anti-alpha1
      chymotrypsin gene from genomic DNA on the In-Check single-use microfabricated
      silicon chip.
AB  - The microfabricated chip is a promising format for automating and miniaturizing
      the multiple steps of genotyping. We tested an innovative silicon biochip (In
      Check Lab-on-Chip; STMicroelectronics, Agrate Brianza, Italy) designed for
      polymerase chain reaction (PCR) analysis of complex biological samples. The chip
      is mounted on a 1x3-in(2). plastic slide that provides the necessary mechanical,
      thermal, electrical, and fluidic connections. A temperature control system drives
      the chip to the desired temperatures, and a graphical user interface allows
      experimenters to define cycling conditions and monitor reactions in real time.
      During thermal cycling, we recorded a cooling rate of 3.2 degrees C/s and a
      heating rate of 11 degrees C/s. The temperature maintained at each thermal
      plateau was within 0.13 degrees C of the programmed temperature at three sensors.
      From 0.5 ng/microl genomic DNA, the In-Check device successfully amplified the
      2060-bp cyanobacterial 16S rRNA gene and the 330-bp human anti-alpha(1)
      chymotrypsin gene. The shortest PCR protocol that produced an amplicon by
      capillary electrophoresis comprised 30 cycles and was 22.5 min long. These
      thermal cycling characteristics suggest that the In-Check device will permit
      future development of a genotyping lab-on-a-chip device, yielding results in a
      short time from a limited amount of biological starting material.

PMID- 16620756
TI  - Real-time monitoring of antibody secretion from hybridomas on a microchip by time
      resolved luminescence anisotropy analysis.
AB  - This article presents a real-time monitoring system for cellular analysis using
      micro total analysis systems technology. Time-resolved luminescence anisotropy
      analysis was adopted for real-time detection of small amounts of a target protein
      produced by a small number of cells. The system was tested by real-time
      monitoring of the antibody secretion by hybridomas. The cells were successfully
      cultivated in a micro-incubation chamber (240 nl) fabricated on a microchip. The
      quantification of the antibody was achieved using the Ru(II) complex-labeled
      Staphylococcus aureus protein A probe, which can bind specifically to the Fc
      region of the antibody. Using this system, we detected as little as 24 fmol of
      immunoglobulin G under physiological conditions without the bound/free separation
      protocol. We successfully achieved real-time and quantitative monitoring of small
      amounts of antibody production by approximately 200 hybridoma cells. This method
      could be applied to various cellular analyses using small numbers of cells.

PMID- 16620757
TI  - A high-throughput assay for a human telomerase protein-human telomerase RNA
      interaction.
AB  - The rapid rate at which cancer cells divide necessitates a mechanism for telomere
      maintenance, and in approximately 90% of all cancer types the enzyme telomerase
      is used to maintain the length of telomeric DNA. Telomerase is a multi-subunit
      enzyme that minimally contains a catalytic protein subunit, hTERT, and an RNA
      subunit, hTR. Proper assembly of telomerase is critical for its enzymatic
      activity and therefore is a requirement for the proliferation of most cancer
      cells. We have developed the first high-throughput screen capable of identifying
      small molecules that specifically perturb human telomerase assemblage. The screen
      uses a scintillation proximity assay to identify compounds that prevent a
      specific and required interaction between hTR and hTERT. Rather than attempting
      to disrupt all of the individual hTR-hTERT interactions, we focused the screen on
      the interaction of the CR4-CR5 domain of hTR with hTERT. The screen employs a
      biotin-labeled derivative of the CR4-CR5 domain of hTR that independently binds
      [(35)S]hTERT in a functionally relevant manner. The complex between hTERT and
      biotin-labeled RNA can be captured on streptavidin-coated scintillation proximity
      beads. Use of 96-well filter plates and a vacuum manifold enables rapid
      purification of the beads. After optimization, statistical evaluation of the
      screen generated a Z' factor of 0.6, demonstrating the high precision of the
      assay.

PMID- 16620758
TI  - Determination of ofloxacin and moxifloxacin and their penetration in human
      aqueous and vitreous humor by using high-performance liquid chromatography
      fluorescence detection.
AB  - Information on comparing the penetration of ofloxacin and moxifloxacin in the
      human eye is unavailable, although these two antibiotics are commonly used in
      ophthalmic surgery. There is a need for a rapid, reliable, and sensitive
      methodology for their determination in ocular fluids. We developed a robust HPLC
      procedure with fluorescence detection for simultaneous analysis of ofloxacin and
      moxifloxacin in human and rabbit aqueous and vitreous samples. The linearity of
      the method ranged from 10 ng/ml to 100 microg/ml with r(2) > 0.996. Most inter-
      and intrabatch imprecision was about 5% (range 1.6-7.6%), recoveries between 95
      and 104%, and accuracies between 93 and 104% at 0.1 and 1 microg/ml. The
      detection limits of both compounds were 10 ng/ml (0.028 nmol/ml for ofloxacin and
      0.023 nmol/ml for moxifloxacin). No sample treatment was necessary for aqueous
      humor and only acetonitrile precipitation was required for vitreous humor. The
      chromatographic time was short, 22 min. We applied this method to study
      penetrations of ofloxacin and moxifloxacin in aqueous and vitreous humors of
      human and rabbits. There was no significant difference of penetration between the
      two antibiotics into aqueous and vitreous but ofloxacin was found at
      significantly higher concentrations in aqueous than in vitreous. We also detected
      contralateral transfer of the antibiotics in rabbit eyes.

PMID- 16620759
TI  - Hand supports to assist toilet use among the elderly.
AB  - Improving the toilet environment holds promises for increasing the quality of
      life for elderly and disabled persons. This is one of the goals of the Friendly
      Rest Room (FRR) project. The study described in this article explored the
      preference and use of supports in the toilet environment during the entire toilet
      ritual. An adjustable test frame was built with a toilet and three types of
      supports. Fourteen subjects were asked which positions they favoured for each
      support. After using all three supports, they were asked which support they found
      most comfortable. In general, the preferred positions depended on personal
      preferences more than on dimensions of the body. It was concluded that there is a
      preference for vertical supports for sitting down and standing up. During toilet
      use the side supports were equally appreciated.

PMID- 16620760
TI  - The C-terminal region of mitochondrial glycerol-3-phosphate acyltransferase-1
      interacts with the active site region and is required for activity.
AB  - Glycerol phosphate acyltransferase (GPAT) catalyzes the formation of 1-acyl-sn
      glycerol-3-phosphate from glycerol-3-phosphate and long chain fatty acyl-CoA
      substrates. We previously determined the topography of the mitochondrial GPAT1
      isoform (mtGPAT1, 828 amino acids). mtGPAT1 has two transmembrane domains (TMDs)
      (aa 472-493 and aa 576-592) with both the N- and C-termini facing the cytosol and
      a loop (aa 494-575) facing the intermembrane space. Alignment of amino acid
      sequences from mtGPAT1 and other acyltransferases and site directed mutagenesis
      studies have demonstrated that the active site of the enzyme resides in the N
      terminal domain of the protein. In this study, we sequentially truncated the C
      terminal domain and characterized the properties of the resulting mutants
      expressed in CHO cells. Although the mutants were overexpressed, none of them
      conferred GPAT activity. The loss of activity was not due to the miss-targeting
      of the proteins since immunofluorescence experiments demonstrated their
      mitochondrial localization. Instead, chemical crosslinking and protein cleavage
      studies demonstrated that the N- and C-termini of the protein interact. These
      results suggest that the C-terminal domain is necessary for mtGPAT1 activity, and
      probably contributes to catalysis or substrate binding.

PMID- 16620761
TI  - The adenosine dimethyltransferase KsgA recognizes a specific conformational state
      of the 30S ribosomal subunit.
AB  - The methyltransferase KsgA modifies two adjacent adenosines in 16S rRNA by adding
      two methyl groups to the N(6) position of each nucleotide. Unlike nearly all
      other rRNA modifications, these modifications and the responsible enzyme are
      highly conserved phylogenetically, suggesting that the modification system has an
      important role in ribosome biogenesis. It has been known for some time that KsgA
      recognizes a complex pre-30S substrate in vitro, but there is disagreement in the
      literature as to what that substrate can be. That disagreement is resolved in
      this report; KsgA is unable to methylate 30S subunits in the translationally
      active conformation, but rather can modify 30S when in an experimentally well
      established translationally inactive conformation. Recent 30S crystal structures
      provide some basis for explaining why it is impossible for KsgA to methylate 30S
      in the translationally active conformation. Previous work identified one set of
      ribosomal proteins important for efficient methylation by KsgA and another set
      refractory methylation. With the exception of S21 the recent crystal structures
      of 30S also instructs that the proteins important for KsgA activity all exert
      their influence indirectly. Unfortunately, S21, which is inhibitory to KsgA
      activity, has not had its position determined by X-ray crystallography. A
      reevaluation of published biophysical data on the location also suggests that the
      refractory nature of S21 is also indirect. Therefore, it appears that KsgA solely
      senses the conformation 16S rRNA when carrying out its enzymatic activity.

PMID- 16620762
TI  - Characterization of RNASET2, the first human member of the Rh/T2/S family of
      glycoproteins.
AB  - Ribonucleases are ubiquitous enzymes involved in RNA metabolism and are
      classified in several families on the basis of their structural, catalytic, and
      biological properties. Here, we describe characterization of the only human
      member of the Rh/T2/S family of acid hydrolases so far described, named RNASET2.
      This protein was previously reported to have an interesting biological function
      in the control of tumourigenesis and metastatization. We show that RNASET2 is
      present in multiple forms in human cell lines and mouse tissues, one of which
      represents the full length, glycosylated and secreted form, while the others are
      proteolytic products. RNASET2 is endowed with catalytic activity as demonstrated
      with purified recombinant protein expressed in the Baculovirus Expression Vector
      System and in a human cell line ectopically expressing various types of
      constructs. Furthermore, we document for this protein a lysosomal localization as
      described for other members of the Rh/T2/S family of ribonucleases. The results
      presented herein represent a further advancement toward the molecular
      understanding of the tumour suppressive properties of the human RNASET2 protein.

PMID- 16620763
TI  - Ceramides reduce CD36 cell surface expression and oxidised LDL uptake by
      monocytes and macrophages.
AB  - Oxidised LDL accumulates in macrophages following scavenger receptor (SR) uptake.
      The expression of the SR, CD36, is increased by oxidised LDL. The signalling
      molecule, ceramide, can modulate intracellular peroxides and increase lipid
      peroxidation. Ceramide also accumulates in atherosclerotic plaques. Thus, we have
      examined whether ceramide can modulate CD36 expression and function in human
      monocyte/macrophages. Addition of synthetic short chain ceramides or the action
      of sphingomyelinase to generate physiological long chain ceramides in situ caused
      significant reductions in CD36 expression by monocytes/macrophages which was not
      due to inhibition of mRNA expression. Inhibition of proteasomal degradation using
      lactacystin had no effect on CD36 expression, however, flow cytometric analysis
      of permeabilised cells suggested an intracellular trafficking blockade. Ceramide
      treated monocytes/macrophages showed dose dependent reduction in oxidised LDL
      uptake. Taken together, it is suggested that ceramide blocks the transport of
      CD36 to the membrane of monocytes/macrophages, thereby preventing uptake of
      oxidised LDL.

PMID- 16620764
TI  - Free radicals in blood: evolving concepts in the mechanism of ischemic heart
      disease.
AB  - There has been a considerable debate over past decade on how reactive oxidant
      species (ROS) in blood augment the cell signaling processes involved in the
      pathogenesis of coronary heart disease. In particular, it is not clear whether
      ROS is an important component of the cross-talk between blood and elements of the
      vasculature during the initial and latter stages of vascular injury and
      development of atherosclerotic lesions. Features like the recruitment of the
      circulating activated monocytes, T cells and granulocytes occur extensively in
      patients with acute coronary syndromes. It is not known what drives the
      infiltration of these cells into the vessel wall in the active stages of
      atherosclerosis and whether ROS plays an intermediate part. Currently, the
      thinking is that although inflammatory processes may be prompted by different
      etiological factors from that of coronary heart disease, the presence of ROS in
      circulating blood is the key intermediary related to vascular injury and organ
      dysfunction. We review, the clinical and experimental data of the mechanisms
      involved, and evaluate the wider implications of this concept.

PMID- 16620765
TI  - C-Terminal truncation of rabbit flavin-containing monooxygenase isoform 2
      enhances solubility.
AB  - Flavin-containing monooxygenases (FMO) are membrane-associated enzymes
      contributing to oxidative metabolism of drugs and other chemicals. There are no
      known structures similar enough to FMO to provide accurate insights into the
      structural basis for differences in metabolism observed among FMOs. To develop an
      FMO amenable to crystallization, we introduced mutations into rabbit FMO2 (rF2)
      to increase solubility, decrease aggregation, and simplify isolation. Alterations
      included removal of 26 AA (Delta26) from the carboxyl-terminus, His(6)-fusion to
      the amino-terminus and a double Ser substitution designed to reduce local
      hydrophobicity. Only Delta26 FMO variants retained normal activity, increased the
      yield of cytosolic rF2 and decreased protein aggregation. Delta26 constructs
      increased rF2 in cytosol in low (from 2 to 13%), and high salt (from 24 to 62%)
      conditions. His-fusion proteins, while active and useful for purification, did
      not affect solubility. Delta26 variants should prove useful for identifying
      conditions suitable for production of an FMO crystal.

PMID- 16620766
TI  - Assembly of single bacteriorhodopsin trimers in bilayer nanodiscs.
AB  - Nanodiscs, phospholipid bilayer assemblies of controlled size, were used to self
      assemble bacteriorhodopsin (bR) into single trimers. Self-assembly at optimal bR
      to Nanodisc and phospholipid stoichiometry yielded particles containing three bR
      molecules. Analysis of solution small angle X-ray scattering indicated that
      bacteriorhodopsin is embedded in a discoidal phospholipid bilayer structure.
      Formation of trimers, as evidenced by visible circular dichroism of the retinal
      absorbance bands, is facilitated in Nanodiscs at a specific size threshold,
      suggesting that a critical bilayer area or amount of lipid is necessary to
      maintain a native oligomeric state. The lipid to bR ratio in the assembly process
      was also found to be an important factor in determining oligomerization state.
      These nanoscale bilayers offer the opportunity to understand and control the
      assembly of oligomeric integral membrane proteins critical to macromolecular
      recognition and cellular signaling.

PMID- 16620767
TI  - Identification of a 115kDa MAP-kinase activated by freezing and anoxic stresses
      in the marine periwinkle, Littorina littorea.
AB  - The mitogen-activated protein kinase (MAPK) cascade regulates changes in gene
      transcription by transmitting extracellular stimuli from the plasma membrane to
      the cell nucleus and has an important role to play in organismal responses to
      environmental stresses. The activities of MAPKs were investigated in the marine
      gastropod mollusk, Littorina littorea, a species that tolerates both
      extracellular freezing and long term oxygen deprivation. In-gel kinase assays
      revealed the presence of two MAPKs in foot muscle and hepatopancreas, a 42 and a
      115kDa protein. Immunoblot analysis showed that both were MAPK proteins and that
      one was the periwinkle homologue of p42(ERK2). Size exclusion chromatography
      confirmed the 115kDa size of the novel snail MAPK and its role as the dominant
      MAPK activity in foot muscle. In-gel kinase assays, immunoblotting with phospho
      specific ERK antibody, as well as kinase activity profiles from hydroxyapatite
      chromatography demonstrated that p115 MAPK kinase activity was increased in foot
      muscle in response to in vivo freezing or anoxia exposures. The results suggest a
      role for this novel kinase in environmental stress response.

PMID- 16620768
TI  - Effects of proteolysis and reduction on phosphatase and ROS-generating activity
      of human tartrate-resistant acid phosphatase.
AB  - Osteoclasts and macrophages express high amounts of tartrate-resistant acid
      phosphatase (TRACP), an enzyme with unknown biological function. TRACP contains a
      disulfide bond, a protease-sensitive loop peptide, and a redox-active iron that
      can catalyze formation of reactive oxygen species (ROS). We studied the effects
      of proteolytic cleavage by trypsin, reduction of the disulfide bond by beta
      mercaptoethanol, and reduction of the redox-active iron by ascorbate on the
      phosphatase and ROS-generating activity of baculovirus-generated recombinant
      human TRACP. Ascorbate alone and trypsin in combination with beta-mercaptoethanol
      increased k(cat)/K(m) of the phosphatase activity seven- to ninefold. The pH
      optimum was changed from 5.4-5.6 to 6.2-6.4 by ascorbate and trypsin cleavage.
      Trypsin cleavage increased k(cat)/K(m) of the ROS-generating activity 2.5-fold
      without affecting the pH-optimum (7.0). These results suggest that the protease
      sensitive loop peptide, redox-active iron, and disulfide bond are important
      regulatory sites in TRACP, and that the phosphatase and ROS-generating activity
      are performed with different reaction mechanisms.

PMID- 16620769
TI  - Defective Mg2+ regulation of RyR1 as a causal factor in malignant hyperthermia.
AB  - In skeletal muscle, Mg(2+) exerts a dual inhibitory effect on RyR1, by competing
      with Ca(2+) at the activation site and binding to a low affinity Ca(2+)/Mg(2+)
      inhibitory site. Pharmacological activators of RyR1 must overcome the inhibitory
      action of Mg(2+) before Ca(2+) efflux can occur. In normal muscle, where the free
      [Mg(2+)](i) is approximately 1mM, even prolonged exposure to millimolar levels of
      volatile anesthetics does not initiate SR Ca(2+) release. However, when the
      cytosolic [Mg(2+)] is reduced below the physiological range, low levels of
      volatile anesthetic within the clinically relevant range (1mM) can initiate SR
      Ca(2+) release, in the form of a propagating Ca(2+) wave. In human muscle fibers
      from malignant hyperthermia susceptible patients, such Ca(2+) waves occur when
      1mM halothane is applied at physiological [Mg(2+)](i). There is increasing
      evidence to suggest that defective Mg(2+) regulation of RyR1 confers
      susceptibility to malignant hyperthermia. At the molecular level, interactions
      between critical RyR1 subdomains may explain the clustering of RyR1 mutations and
      associated effects on Mg(2+) regulation.

PMID- 16620770
TI  - Effect of construct design on MAPKAP kinase-2 activity, thermodynamic stability
      and ligand-binding affinity.
AB  - MAPK-activated protein kinase-2 (MAPKAPK2) regulates the synthesis of tumor
      necrosis factor and other cytokines and is a potential drug target for
      inflammatory diseases. Five protein constructs were produced in 4-10mg quantities
      per liter of culture media using baculovirus-infected insect cells and
      characterized for kinase activity, thermal stability, and ligand-binding
      affinity. Compared to construct 1-370, removal of the C-terminal autoinhibitory
      peptide in 1-338 resulted in a destabilized but partially active
      nonphosphorylated enzyme; phosphorylation of 1-338 by p38alpha further increased
      activity 12-fold. A putative constitutively active mutant, 1-370/T222E/T334E, was
      6.3-fold less active than phosphorylated 1-370. ThermoFluor, an equilibrium
      ligand-binding assay, was used to measure nucleotide analogue affinity for
      various constructs. Binding of phosphorylated nucleotides was Mg(2+)-dependent.
      Residues 1-40 were required for high-affinity binding of ADP, ATPgammaS,
      staurosporine, and K252a. A mutation M138A rendered 1-370 susceptible to p38
      inhibitors SB-203580 and SB-202190 with IC50 values of 17.4 and 14.1 microM,
      respectively. Taken together, these studies provide information on the mechanism
      of ligand-binding to MAPKAPK2 that can be used in the search for selective small
      molecule inhibitors.

PMID- 16620771
TI  - Functional characterization of human 1-acylglycerol-3-phosphate acyltransferase
      isoform 8: cloning, tissue distribution, gene structure, and enzymatic activity.
AB  - Glycerophospholipids and triglycerides are synthesized de novo by cells through
      an evolutionary conserved process involving serial acylations of phosphorylated
      glycerol. Various isoforms of the enzyme, 1-acylglycerol-3-phosphate
      acyltransferase (AGPAT), acylate lysophosphatidic acid at the sn-2 position to
      produce phosphatidic acid. We cloned a cDNA predicted to be AGPAT isoform and
      designated it AGPAT8. Human and mouse AGPAT8 proteins are 89% homologous, and
      their gene structure is also highly conserved. AGPAT8 is most closely related to
      AGPAT5, and its cDNA is expressed most in the heart, while AGPAT5 is expressed
      more in the prostate and testis. In cell lysates, AGPAT8 shows moderate
      acyltransferase activity with [(3)H]oleoyl-CoA but lacks acyl-CoA:lysocardiolipin
      acyltransferase activity. In whole cells upon incubation with [(14)C]linoleic
      acid, most of the radioactivity was recovered in phosphatidyl ethanolamine,
      phosphatidyl choline and phosphatidic acid fraction. Of the two well conserved
      acyltransferase motifs, NHX(4)D is present in AGPAT8, whereas arginine in the
      EGTR motif is substituted by aspartate. However, mutation of EGTD to EGTR did not
      increase enzymatic activity significantly. Based on the X-ray crystallographic
      structure of a related acyltransferase, squash gpat, a model is proposed in which
      a hydrophobic pocket in AGPAT8 accommodates fatty acyl chains of both substrates
      in an orientation where the NHX(4)D motif participates in catalysis.

PMID- 16620772
TI  - A general approach for investigating enzymatic pathways and substrates for
      ubiquitin-like modifiers.
AB  - Ubiquitin-like modifiers (UBLs) contain ubiquitin homology domains and can
      covalently modify target proteins in a manner similar to ubiquitylation. In this
      study, we revealed a general proteomic approach to elucidate the enzymatic
      pathways and identify target proteins for three UBLs: SUMO-2, SUMO-3, and NEDD8.
      Expression plasmids containing the cDNAs of Myc/6xHis doubly-tagged processed or
      non-conjugatable forms of these UBLs were constructed. The constructed vectors
      were then used to transfect HEK 293 Tet-On cells, and stable cell lines
      expressing these UBLs and their mutants were established. The epitope-tagged
      proteins were purified by immunoprecipitation under native conditions or by
      affinity chromatography on nickel resin under denaturing conditions. Purified
      proteins were analyzed using liquid chromatography coupled with mass spectrometry
      (LC-MS/MS). Most of the E1-like activating enzymes, E2-like conjugating enzymes
      and the majorities of the known target as well as some previously unreported
      proteins for SUMO-2, SUMO-3, and NEDD8 pathways were identified.

PMID- 16620773
TI  - Facial nerve section induces transient changes in sensitivity to methacholine and
      in acetylcholine synthesis in the rat parotid gland.
AB  - Nerves exert long-term influences on the salivary glands as e.g. revealed by
      increases in sensitivity to secretagogues following nerve degeneration. The
      objective was to study the effect of unilateral facial nerve section on the
      sensitivity of the parotid secretory cells 2-3 weeks postoperatively, i.e. at a
      time when the sensitisation is thought to be fully developed. Comparisons were
      made between pair of glands. However, no increase in the secretory response to
      increasing intravenous doses of methacholine of the duct-cannulated gland on the
      operated side was found; neither were any decrease in the acetylcholine
      synthesizing capacity of the gland found. In contrast, a slight supersensitivity
      had developed 1 week postoperatively supporting the idea of a functional
      influence of the facial nerve on the secretory cells under normal conditions.
      Furthermore, the results combined with the previous finding of ours of decreased
      acetylcholine synthesis in the parotid gland 1 week after facial nerve section,
      suggest a rapid restitution of the nervous influence on the secretory cells
      between 1 and 2-3 weeks postoperatively.

PMID- 16620774
TI  - A new technique for symmetry determination in tooth morphology using image
      analysis: application in the diagnosis of solitary maxillary median central
      incisor.
AB  - OBJECTIVE: To develop a new technique for determining symmetry in tooth
      morphology and to evaluate this in the investigation of a patient with a solitary
      maxillary median central incisor (SMMCI) and a control group. DESIGN: A 9-year
      old Caucasian female presented with SMMCI. Clinically the tooth appeared
      symmetrical. Morphology measurements of the maxillary central incisor were made
      using an image analysis system. Symmetry was determined by outlining the tooth
      from labial and axial views. These images were block filled, duplicated, flipped
      horizontally and then superimposed on the original image. The coincident area and
      perimeter of the two images from both views were measured. The method was
      repeated for the maxillary central incisors of 20 sets of control study models
      for young adult patients from which reference intervals for comparison with the
      SMMCI case were prepared. RESULTS: From the labial view, the area and perimeter
      of the two images of the SMMCI tooth were 98.85% and 98.97% coincident,
      respectively. From the axial view the area of the two images was 96.17%
      coincident, while the perimeter was 99.03% coincident. In all but one comparison
      for coincidence the SMMCI was above the upper limit of the reference range from
      the control group. CONCLUSIONS: This new technique is a valid method of assessing
      symmetry and is a useful clinical tool in cases of SMMCI.

PMID- 16620775
TI  - Effect of oral bacteria on growth and survival of Candida albicans biofilms.
AB  - The purpose of this study was to evaluate the effect of eight aerobic and
      anaerobic oral commensal bacterial species on in vitro Candida albicans biofilm
      development. A single isolate of C. albicans 2560 g, and eight different species
      of oral bacteria comprising, Actinomyces israelii, Lactobacillus acidophilus,
      Prevotella nigrescens, Porphyromonas gingivalis, Pseudomonas aeruginosa,
      Escherichia coli, Streptococcus mutans, and Streptococcus intermedius were
      studied using an in vitro biofilm assay. Biofilm formation was quantified in
      terms of the ability of Candida to grow on polystyrene plastic surfaces co
      cultured with the foregoing bacteria. A viable cell count was used to quantify
      the sessile yeast growth and scanning electron microscopy was employed to confirm
      and visualize biofilm formation. Co-culture with differing concentrations of
      bacteria had variable effects on Candida biofilm formation. Co-culture with the
      highest concentrations of each of the foregoing bacteria resulted in a consistent
      reduction in the yeast counts in the candidal biofilm (P<0.05), except for L.
      acidophilus, S. mutans, and, S. intermedius co-cultures. Further, on regression
      analysis a significant negative correlation between the co-culture concentration
      of either P. gingivalis or E. coli and viable yeast counts in the biofilm was
      noted (P<0.05) although this was not evident for the other bacterial species.
      Taken together, our data indicate that, quantitative and qualitative nature of
      the bacteria modulate C. albicans biofilm formation in mixed species environments
      such as the oral cavity.

PMID- 16620776
TI  - Free radicals related effects and antioxidants in saliva and serum of adolescents
      with Type 1 diabetes mellitus.
AB  - OBJECTIVE: The purpose of the current study was to analyze both serum and
      salivary composition and oxidative stress markers in Type 1 diabetes mellitus
      (DM) patients. DESIGN: Twenty consenting patients with DM but otherwise healthy
      patients aged 13-19 years and 12 healthy controls, matching in age and gender
      (Group 1), participated in the study. The patients were divided according to
      those who had controlled diabetes mellitus (Group 2) or uncontrolled diabetes
      mellitus (Group 3). All were analyzed for saliva composition and antioxidants.
      Saliva was also analyzed for its levels of superoxide dismutase (SOD) and amylase
      activity, total IgA and total IgG concentrations and potassium, phosphorus,
      magnesium and calcium electrolyte concentrations. RESULTS: A significant
      correlation was found between the severity of the DM/HbA1c values and the
      increase in both salivary and/or serum antioxidants (peroxidase, SOD and TAS),
      and the various TCL parameters (H1, H3, pre-incubation and oxygenation
      potential). CONCLUSIONS: The two most important findings of the current study
      relate to the role of oxidative stress in the pathogenesis of Type 1 diabetes
      mellitus and to the involvement of salivary glands in the disease. The profound
      effects of DM on salivary antioxidant parameters may be also of great importance
      in respect to the diagnosis and evaluation of the disease. The correlation
      between altered salivary parameters and the severity of the disease may indicate
      that evaluation of the salivary status of DM patients as part of the assessment
      of their disease activity and severity is warranted.

PMID- 16620777
TI  - Scanning electron microscopy of the three different types of cementum in the
      molar teeth of the guinea pig.
AB  - The aim of this study was to observe the three-dimensional distribution and
      structural characteristics of the three different types of cementum in the molar
      teeth of guinea pig by means of scanning electron microscopy. Twenty-five 4-week
      old male guinea pigs were used in this study. Using decalcified and undecalcified
      specimens with or without NaOH maceration, we examined the mandibles, maxillae
      and extracted molars by scanning electron microscopy. Guinea pig molars consist
      of two longitudinal, deeply folded lamina cores covered by enamel on all
      surfaces, except the buccal surface of the upper molars and the lingual surface
      of the lower molars. In the regions without enamel, we observed continuous thin
      belt-like layers of conventional acellular cementum on the dentin surface. On the
      enamel-covered surfaces, two different types of coronal cementum were found:
      small circular islands of coronal cementum called cementum pearls, which were
      distributed widely at almost regular intervals on the peripheral enamel surface
      from the apical fifth to the occlusal surface; and cartilage-like cementum, which
      occupied almost all of the occlusal half of the two longitudinally folded
      grooves. The present study demonstrated the unique distribution pattern of the
      three different types of cementum in guinea pig molars. These cementum types may
      contribute to the requirements for many different functions such as mastication,
      anchorage and continuous tooth eruption.

PMID- 16620778
TI  - Paxillin phosphorylation and integrin expression in osteoblasts infected by
      Porphyromonas gingivalis.
AB  - OBJECTIVE: We investigated early biological events initiated by Porphyromonas
      gingivalis infection of human osteoblasts, focusing on tyrosine-phosphorylation
      and the expression of key components in focal adhesion and cell signalling.
      DESIGN: Human primary osteoblasts were challenged for 1h with Porphyromonas
      gingivalis. Tyrosine-phosphorylation of paxillin and focal adhesion kinase (FAK)
      was examined by Western blotting. Changes in alpha3- and beta1-integrin mRNA
      expression were quantified by RT-PCR. RESULTS: Tyrosine-phosphorylation of
      paxillin was proportional to the size of the Porphyromonas gingivalis inoculum.
      FAK, a potential kinase for paxillin, was not activated. The amount of alpha3-
      and beta1-integrins, determined by Western blotting, did not vary significantly,
      while the corresponding mRNA levels fell significantly when a large bacterial
      inoculum was used. CONCLUSIONS: These results indicate that Porphyromonas
      gingivalis infection of osteoblasts in vitro triggers tyrosine-phosphorylation of
      paxillin but not FAK and modify alpha3- and beta1-integrin mRNA expression. This
      infection thus appears to have different effects on components with essential
      roles in focal adhesion (paxillin) and cell signalling (FAK and integrins).

PMID- 16620779
TI  - Understanding cognitive behaviour therapy: A retrieval competition account.
AB  - Vulnerability to emotional disorders is thought to lie in memory representations
      (e.g. negative self-schemas) that are activated by triggering events and maintain
      negative mood. There has been considerable uncertainty about how the influence of
      these representations can be altered, prompted in part by the development of new
      metacognitive therapies. This article reviews research suggesting there are
      multiple memories involving the self that compete to be retrieved. It is proposed
      that CBT does not directly modify negative information in memory, but produces
      changes in the relative activation of positive and negative representations such
      that the positive ones are assisted to win the retrieval competition. This
      account is related to the treatment of common symptoms typical of emotional
      disorders, such as phobic reactions, rumination, and intrusive images and
      memories. It is shown to provide a parsimonious set of principles that have the
      potential to unify traditional and more modern variants of CBT.

PMID- 16620780
TI  - HGF-induced capillary morphogenesis of endothelial cells is regulated by Src.
AB  - The signal transduction pathway involved in hepatocyte growth factor (HGF)
      induced capillary morphogenesis of endothelial cells was investigated. HGF
      induced capillary morphogenesis of the murine spleen endothelial cell line MSS31
      was inhibited by a Src family kinase inhibitor, PP2. Stable expression of kinase
      inactive Src in MSS31 cells inhibited HGF-induced activation of Src as well as
      capillary morphogenesis. The HGF-induced capillary morphogenesis of human
      umbilical vein endothelial cells was also inhibited by PP2 and was reduced by the
      downregulation of Src by small interfering RNA. These results suggest that HGF
      induces capillary morphogenesis of endothelial cells through Src.

PMID- 16620781
TI  - Non-coding transcripts far upstream of the epsilon-globin gene are distinctly
      expressed in human primary tissues and erythroleukemia cell lines.
AB  - Non-coding exons of epsilon-globin mRNA originating within the 236 kb upstream
      region of the epsilon-globin gene were identified in human primary tissues and
      K562 cells. One predominant type of upstream epsilon mRNA, which originated in
      the -76 kb region 5' to the epsilon gene, was present in human primary tissues,
      whereas 11 other isoforms were identified in K562 cells. Fragment from the -76 kb
      region possessed promoter activity and a prominent DNase I hypersensitive site
      was formed in the region approximately 2 kb 5' to the -76 kb promoter in human
      fetal liver, but not in K562 cells. The promoter activity in the -236 kb region
      resided in a retrotransposon in K562 cells. A DNase I hypersensitive site was
      formed at the -236 kb promoter in K562 cells, but not in human fetal liver. We
      discussed these results in the context of intergenic transcription and chromatin
      opening in the beta-globin gene cluster.

PMID- 16620782
TI  - Knockdown of apolipoprotein B, an atherogenic apolipoprotein, in HepG2 cells by
      lentivirus-mediated siRNA.
AB  - ApoB is an important determinant of atherosclerosis susceptibility and a
      potential pharmaceutical target for lowering atherogenic lipoproteins. In the
      present study, we used a lentiviral vector to express short hairpin RNAs for
      inhibition of apoB production in HepG2 cells. We first demonstrated that
      lentivirus could efficiently deliver transgene into HepG2 cells by using GFP
      lentivirus. We then made three lentiviral siApoB constructs, two of which were
      highly efficient for silencing apoB expression in HepG2 cells. We showed that
      siApoB lentivirus specifically knocked down apoB but had no effects on other
      proteins such as apoAI and albumin. Consequently, the secretion of apoB was
      reduced markedly. The silencing effect of siApoB lentivirus appeared to be
      permanent. Knocking down apoB did not alter the expression of cytoplasmic stress
      proteins (HSP70 and HSP90) and their ER homologues (GRP78 and GRP94).
      Furthermore, neither IKKalpha and JNK nor phosphorylated IKK and JNK were
      increased in long-term apoB-deficient hepatocytes as compared to the control
      cells. Consistent with these findings, apoB-deficient hepatocytes responded to
      insulin to a similar extent as the control cells as determined by measuring
      insulin-induced phosphorylation of IRS and ERK. Our studies indicate that
      lentiviral siRNAs provide an excellent approach for delivering siRNA into HepG2
      cells and may be used for gene therapy for hyperlipidemia.

PMID- 16620783
TI  - Intestinal neuro-epithelial interactions modulate neuronal chemokines production.
AB  - Human enteric neurons have recently been shown to produce chemokines during
      intestinal inflammation. However, whether (1) neuro-epithelial interactions
      modulate neuronal chemokines production and (2) neurons can induce the chemotaxis
      of immune cells remain unknown. Neuro-epithelial interactions were studied using
      a coculture model composed of human neurons (NT2-N) and intestinal epithelial
      cells (Caco-2). IL-8 or MIP-1beta expression was analyzed by quantitative-PCR,
      ELISA or immunohistochemistry. Neuronally induced chemotaxis was studied using a
      coculture model composed of NT2-N and human peripheral blood mononuclear cells
      (PBMC). Following Caco-2 inflammation with IFNgamma/TNFalpha, neuronal IL-8 and
      MIP-1beta mRNA expression was significantly increased compared to control. This
      increase was significantly reduced by IL-1 receptor antagonist. IL-1beta
      pretreated NT2-N induced the chemotaxis of PBMC, which was significantly reduced
      by anti-IL-8, but not by anti-MIP-1beta neutralizing antibody. Our results
      demonstrate that, under inflammatory conditions, neuro-epithelial interactions
      can modulate neuronal chemokines production through IL-1beta-dependent pathways.
      Furthermore, neuronal IL-1beta-induced chemotactic properties could favor the
      development of immune cells infiltrates within the enteric nervous system, as is
      observed during intestinal inflammation.

PMID- 16620784
TI  - Effect of short-term and long-term fasting on transcriptional regulation of
      metabolic genes in rat tissues.
AB  - Ninety-eight genes/ESTs with differential expressions in epididymal adipose
      tissue of fed and 3-day fasting (F3) rats were identified by microarray analysis.
      Genes for lipogenesis, glycolysis, and glucose aerobic oxidation were decreased
      in response to starvation. Further study was performed to investigate the
      expression patterns of these genes in rat tissues after short- and long-term
      starvations. The results of the increased expression of the pyruvate
      dehydrogenase kinase 4 (PDK4) gene and decreased pyruvate dehydrogenase (PDH) in
      rat muscle together with decreased fatty acid synthase (FAS) in rat adipose
      tissue after 1 day of fasting (F1) suggested from transcriptional level that
      glucose aerobic oxidation was down-regulated in rat muscle and synthesis of
      saturated fatty acids was inhibited in rat adipose tissue after short-term
      fasting. It was noted that the transcriptions of genes involved in the fatty acid
      oxidation, such as very-long-chain Acyl-CoA dehydrogenase (LCAH), Acyl-CoA
      oxidase (ACO), carnitine palmitoyltransferase-I (CPT-I), and carnitine
      acylcarnitine translocase (CAT)L, were greatly increased in F1 rat liver, then
      began to decrease in F3 and 5-day fasting (F5) rat liver, combined with
      significantly increased serum non-esterified fatty acids (NEFA) in F1 rats and
      increased urea in F5 rats, suggesting that inhibition of the oxidation of lipid
      and not the decreased availability of these fuels may play an important role in
      the phase II-phase III of fasting transition in the long-term fasting rats.

PMID- 16620786
TI  - Chemical modification at subunit 1 of rat kidney Alpha class glutathione
      transferase with 2,3,5,6-tetrachloro-1,4-benzoquinone: close structural
      connectivity between glutathione conjugation activity and non-substrate ligand
      binding.
AB  - 2, 3, 5, 6-Tetrachloro-1, 4-benzoquinone (TCBQ) is a metabolite of
      pentachlorophenol known to react with cysteines of glutathione transferases
      (GSTs). TCBQ treatment of rat kidney rGSTA1-2 and rGSTA1-1 abolishes 70-80%
      conjugation of glutathione (GSH) to 1-chloro-2, 4-dinitrobenzene and results in
      strongly correlated quenching of intrinsic fluorescence of Trp-20 (R>0.96).
      rGSTA2-2 is only inhibited by 25%. Approximately 70% (rGSTA1-1) and 60% (rGSTA1
      2) conjugation activity is abolished at TCBQ: GST stoichiometries near 1:1. The
      inactivation follows a Kitz/Wilson model with K(D) of 4.77+/-2.5microM for TCBQ
      and k(3) for inactivation of 0.036+/-0.01min(-1). A single tryptic peptide
      labelled with TCBQ was isolated from kidney rGSTA1-2 containing Cys-17 which we
      identify as the site of modification. Treatment with more than stoichiometric
      amounts of TCBQ modified other residues but resulted in only modest further
      inhibition of catalysis. We interpret these findings in terms of localised steric
      effects on the relatively rigid alpha-helix 1 adjacent to the catalytic site of
      subunit 1 possibly affecting the Alpha class-specific alpha-helix 9 which acts as
      a "lid" on the hydrophobic part of the active site. Homology modelling of rGSTA1
      1 modified at Cys-17 of one subunit revealed only modest structural perturbations
      in the second subunit and tends to exclude global structural effects.

PMID- 16620785
TI  - AMP-activated protein kinase (AMPK) activating agents cause dephosphorylation of
      Akt and glycogen synthase kinase-3.
AB  - AMP-activated protein kinase (AMPK) is a key cellular sensor of reduced energy
      supply that is activated by increases in the cellular ratio of AMP/ATP.
      Phenformin and 5-aminoimidazole-4-carboxamide riboside (AICAR) are two drugs
      widely used to activate AMPK experimentally. In both differentiated hippocampal
      neurons and neuroblastoma SH-SY5Y cells we found that these two agents not only
      activated AMPK, but conversely greatly reduced the activating Ser/Thr
      phosphorylation of Akt. This blockade of Akt activity consequently lowered the
      inhibitory serine-phosphorylation of its substrates, glycogen synthase kinase
      3alpha/beta (GSK3alpha/beta). An inhibitor of AMPK (Compound C) did not block
      dephosphorylation of Akt and GSK3. Thus, both drugs widely used to activate AMPK
      also caused dephosphorylation of Akt and of GSK3. The mechanism for Akt
      dephosphorylation caused by phenformin, but not AICAR, was due to inhibition of
      growth factor-induced signaling that leads to Akt phosphorylation. Stimulation of
      muscarinic receptors with carbachol in SH-SY5Y cells also activated AMPK and
      transiently caused dephosphorylation of Akt. These findings show that Akt
      dephosphorylation often occurs concomitantly with AMPK activation when cells are
      treated with phenformin or AICAR, indicating that these drugs do not only affect
      AMPK but also cause a coordinated inverse regulation of AMPK and Akt.

PMID- 16620787
TI  - Vincristine transcriptional regulation of efflux drug transporters in carcinoma
      cell lines.
AB  - The increased expression of drug transporters following cancer chemotherapy
      contributes to resistance. This may reflect transcriptional up-regulation and/or
      clonal selection. We quantified the expression of mRNA for ABCB1 (mdr1), ABCC1
      (mrp1), ABCC2 (mrp2) and ABCC3 (mrp3) to evaluate the potential contribution of
      induction. ABCB1, ABCC1-3 mRNAs were quantified by real time RT-PCR and
      normalized to GAPDH. We used intestinal cells that express high pregnane X
      receptor (LS174T), low pregnane X receptor (Caco-2) and lung cells (A549) that
      express glucocorticoid receptor and low pregnane X receptor. Rifampin (10 microM)
      caused significant induction of ABCB1 (595+/-263%, p<0.05) in LS174T cells but
      induction was absent in Caco-2 or A549 cells. ABCC1 was not induced in any cell
      at 24, 48 and 72 h following rifampin treatment. In contrast, vincristine (10 nM
      and 100 nM), a ligand for ABCB1 and ABCC1-3 and a potential PXR/CAR ligand,
      induced ABCC2 and ABCC3 expression in LS174T cells at 48 h (372+/-87% and 303+/
      42%, respectively, p<0.05). A similar induction of ABCC2 and ABCC3 genes was also
      seen with 10 nM VCR in A549 cells following 48 h treatment. In summary, there may
      be a significant contribution of transcriptional activation to multi-drug
      resistance. However, this is cell selective and is not necessarily dependent on
      PXR mediated effects.

PMID- 16620788
TI  - Structure-activity relationship for nucleoside analogs as inhibitors or
      substrates of adenosine kinase from Mycobacterium tuberculosis. I. Modifications
      to the adenine moiety.
AB  - Adenosine kinase (Ado kinase, EC 2.7.1.20) is a purine salvage enzyme that
      phosphorylates adenosine (Ado) to AMP. Ado kinase from Mycobacterium tuberculosis
      also catalyzes an essential step in the conversion of 2-methyl-Ado to a compound
      with selective antimycobacterial activity. In order to aid in the design of more
      potent and selective Ado analogs, eighty nucleoside analogs with modifications to
      the adenine (Ade) moiety of Ado were evaluated as both substrates and inhibitors
      of Ado kinase from M. tuberculosis, and a subset was further tested with human
      Ado kinase for the sake of comparison. The best substrates were 2-aza-Ado, 8-aza
      9-deaza-Ado, and 2-fluoro-Ado and the most potent inhibitors were N1-benzyl-Ado
      (Ki=0.19 microM), 2-fluoro-Ado (Ki=0.5 microM), 6-cyclopentyloxy-purine riboside
      (Ki=0.15 microM), and 7-iodo-7-deaza-Ado (Ki=0.21 microM). These studies revealed
      the presence of a hydrophobic pocket near the N6- and N1-positions that can
      accommodate substitutions at least as large as a benzyl group. The ability to fit
      into this pocket increased the likelihood that a compound would be an inhibitor
      and not a substrate. The 2-position was able to accommodate exocyclic
      substitutions as large as a methoxy group, although substrate activity was low.
      Similarly, the 7-position could bind an exocyclic group as large as a carboxamido
      moiety. However, all of the compounds tested with modifications at the 7-position
      were much better inhibitors than substrates. MIC studies performed with selected
      compounds have yielded several Ado analogs with promising antitubercular
      activity. Future studies will utilize this information for the design of new
      analogs that may be selective antitubercular agents.

PMID- 16620789
TI  - Radiolytic and cellular reduction of a novel hypoxia-activated cobalt(III)
      prodrug of a chloromethylbenzindoline DNA minor groove alkylator.
AB  - Metabolic reduction can be used to activate prodrugs in hypoxic regions of
      tumours, but reduction by ionising radiation is also theoretically attractive.
      Previously, we showed that a cobalt(III) complex containing 8-hydroxyquinoline (8
      HQ) and cyclen ligands releases 8-HQ efficiently on irradiation in hypoxic
      solutions [Ahn G-O, Ware DC, Denny WA, Wilson WR. Optimization of the auxiliary
      ligand shell of cobalt(III)(8-hydroxyquinoline) complexes as model hypoxia
      selective radiation-activated prodrugs. Radiat Res 2004;162:315-25]. Here we
      investigate an analogous Co(III) complex containing the potent DNA minor groove
      alkylator azachloromethylbenzindoline (azaCBI, 1) to determine whether it
      releases 1 on radiolytic and/or enzymatic reduction under hypoxia. Monitoring by
      HPLC, the azaCBI ligand in the Co(III)(cyclen)(azaCBI) complex (2) slowly
      hydrolysed in aqueous solution, in contrast to the free ligand 1 which readily
      converted to its reactive cyclopropyl form. Irradiation of 2 (30-50 microM) in
      hypoxic solutions released 1 with yields of 0.57 micromol/J in formate buffer and
      0.13 micromol/J in human plasma. Using bioassay methods, cytotoxic activation by
      irradiation of 2 at 1 microM in hypoxic plasma was readily detectable at
      clinically relevant doses (> or = 1 Gy), with a estimated yield of 1 of 0.075
      micromol/J. Release of 1 from 2 was also observed in hypoxic HT29 cultures
      without radiation, with subsequent conversion of 1 to its O-glucuronide.
      Surprisingly, overexpression of human cytochrome P450 reductase in A549 cells did
      not increase the rate of metabolic reduction of 2, suggesting that other
      reductases and/or non-enzymatic reductants are responsible. Thus the cobalt(III)
      complex 2 is a promising prodrug capable of being activated to release a very
      potent cytotoxin when reduced by either ionising radiation or cells under hypoxic
      conditions.

PMID- 16620790
TI  - TGF-beta in cancer and as a therapeutic target.
AB  - Cancer develops through a series of genetic changes leading to malignant
      transformation. Numerous gene and pathways involved in stages of progression to
      frank malignancy have been elucidated. These genetic changes result in
      aberrations in fundamental cellular processes controlling proliferation,
      apoptosis, differentiation and genomic stability. Metastasis is the hallmark of
      malignancy. The process of metastasis is extremely complex and involves steps
      including dissemination of tumor cells from the primary tumor through the
      vascular and lymphatic system and growth selectively in distant tissues and
      organs. Transforming growth factor-beta which is a growth suppressive cytokine in
      many normal situations becomes an active and important participant in malignant
      disease including angiogenesis, extracellular matrix deposition, immuno
      suppression and metastasis growth promotion. Transforming growth factor-beta and
      its receptors are targets for antibody therapeutics and small molecule kinase
      inhibitors.

PMID- 16620791
TI  - Synergism between staurosporine and drugs inducing endoplasmic reticulum stress.
AB  - Drugs causing endoplasmic reticulum or mitochondrial dysfunction may trigger
      apoptosis in eukaryotic cells. The thiol reagent dithiothreitol (DTT) belongs to
      the first group whereas the protein kinases inhibitor staurosporine acts on
      mitochondria. Since the endoplasmic reticulum and the mitochondrial pathways of
      apoptosis may converge in common steps, we examined the possibility of synergism
      between these two drugs. Using the activation of caspase-3 as indicator of
      apoptosis, we found that in two cell lines, Jurkat and Mono-Mac 6, staurosporine
      and DTT elicited apoptosis with a different pattern: staurosporine acted rapidly
      and at nanomolar concentrations while DTT acted slowly and at higher
      concentrations (1mM). When staurosporine and DTT were combined, the proapoptotic
      action was increased. This was confirmed examining late apoptotic events such as
      the translocation of phosphatidylserine across the plasma membrane and the
      cleavage of the antiapoptotic protein Mcl-1. The use of subthreshold DTT
      concentrations and isobologram analysis demonstrated the synergic nature of the
      interaction. Tunicamycin, a drug that, like DTT, inhibits protein folding in the
      endoplasmic reticulum also increased the proapoptotic effect of staurosporine. In
      agreement with the interplay between the mitochondrial and the endoplasmic
      reticulum pathways it was found that both staurosporine and DTT induced
      cytochrome c release. Furthermore, 90min incubation with DTT did not induce
      caspase-4 activation while staurosporine alone or in combination with DTT
      stimulated caspase-4 activity. We conclude that staurosporine is more active in
      cells undergoing endoplasmic reticulum stress. This synergism may warrant
      evaluation to establish whether the anticancer activity of staurosporine is also
      enhanced.

PMID- 16620792
TI  - Alkylating drugs applied in non-cytotoxic doses as a novel compounds targeting
      inflammatory signal pathway.
AB  - Alkylating drugs (ADs) belonging to the nitrogen mustard family are commonly used
      as cytostatic and immunosuppressive agents. Our previous in vitro studies
      demonstrated that in the case of gradual dose decrease, the number of targets for
      alkylation in the cell is also reduced and the drug switches from brutal
      cytostatic to cell growth modifier. At doses of 0.3 microg/ml and lower, the
      effects of ADs are no longer associated with DNA damage or stress/MAPK pathways
      activation. Instead, the disruption of signal transduction by the IL-2beta and/or
      TNFalpha cell surface receptors is observed. As a result, ADs in the doses 100
      fold lower than cytostatic ones are capable to modify lymphocyte activity
      including the activity of regulatory T cells. We hypothesized that ADs may have a
      beneficial effect in the treatment of inflammatory diseases. Indeed, the
      application of non-cytotoxic doses of an AD melphalan reduces the severity of
      murine experimental colitis. Daily administration of melphalan (25 microg/kg body
      weight) markedly reduced the severity of DSS-colitis as determined by clinical
      and histological criteria. Moreover, the beneficial effect of melphalan was also
      shown in asthmatic patients. In 60% of these patients histological and
      ultrastructural signs of bronchial epithelium regeneration were also revealed.
      Thus, ADs at non-cytotoxic concentrations exert beneficial effect both in acute
      and chronic inflammatory diseases. Such anti-inflammatory activity is thought to
      be due to blocking of signal transduction through various cell surface receptor
      including IL-2R and TNFR. Consequently different steps of inflammatory cascade
      turn out to be inhibited.

PMID- 16620793
TI  - Membrane cholesterol contents influence the protective effects of quercetin and
      rutin in erythrocytes damaged by oxidative stress.
AB  - Flavonoids are potent scavengers of reactive oxygen species (ROS) that
      effectively prevent erythrocyte oxidation. Their antioxidant activities are
      governed by their structural characteristics and their ability to interact with
      and penetrate lipid bilayers. In order to gain a better understanding of the
      relationship between cholesterol contents and the antioxidant effectiveness of
      flavonoids against oxidative damage induced by ROS in cells, here we analyzed the
      integrity and structural stability of cholesterol-modified (enriched or depleted)
      and control erythrocytes exposed to tert-butyl hydroperoxide in the presence of
      quercetin or rutin. In control and cholesterol-enriched erythrocytes, quercetin
      provided greater protection against lipid peroxidation, ROS formation, and it
      preserved better cellular integrity than rutin. Both antioxidants suppressed the
      alterations in membrane fluidity and lipid losses with similar efficiency,
      reducing hemoglobin oxidation by 30% and GSH losses by 60% in the above-mentioned
      erythrocytes. Cholesterol depletion reduced the efficiency of the antioxidant
      power of both flavonoids against oxidative damage induced in the erythrocyte
      membrane, while a stronger degree of protection of GSH and hemoglobin contents
      was observed, mainly in the presence of rutin. These findings suggest a
      preferential incorporation of the antioxidants into the membranes from
      erythrocytes with normal and high cholesterol contents, whereas they would mainly
      be located in the cytoplasm of cholesterol-depleted erythrocytes.

PMID- 16620794
TI  - Effects of pentachlorophenol on the reproduction of Japanese medaka (Oryzias
      latipes).
AB  - Pentachlorophenol (PCP) is widely used to control termites and protect wood from
      fungal-rot and wood-boring insects, and is often detected in the aquatic
      environment. Few studies have evaluated PCP as an environmental endocrine
      disruptor. In the present work, Japanese medaka (Oryzias latipes) was exposed to
      PCP for 28 days (F0 generation) with subsequent measurements of vitellogenin
      (VTG), hepatic 7-ethoxyresorufin-O-deethylase (EROD), and reproductive endpoints.
      Plasma VTG significantly increased in male fish treated with PCP concentrations
      lower than 200 microg/l and decreased in male and female animals exposed to 200
      microg/l. Hepatic EROD from female fish increased when PCP exposure
      concentrations exceeded 20 microg/l, but decreased in the 200 microg/l PCP
      treatment group. Fecundity and mean fertility of female medaka decreased
      significantly in the second and third week following exposure concentrations
      greater than 100 microg/l, and testis-ova of male medaka was observed at PCP
      concentrations greater than 50 microg/l. Histological lesions of liver and kidney
      occurred when exposure concentrations exceeded 50 microg/l. In F1 generations,
      the hatching rates and time to hatch of offspring were significantly affected in
      fish exposed to 200 microg/l. These results indicated that PCP exposure caused
      responses consistent with estrogen and aryl hydrocarbon receptor activation as
      well as reproductive impairment at environmentally relevant concentrations.

PMID- 16620795
TI  - The organoselenium compound 1,4-phenylenebis(methylene)selenocyanate inhibits 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced tumorgenesis and enhances
      glutathione-related antioxidant levels in A/J mouse lung.
AB  - Selenium, in the form of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) but not
      Se-enriched yeast (Se-yeast), was highly effective at inhibiting lung tumors
      induced by the tobacco specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) in A/J mice and at reducing NNK-induced DNA methylation
      and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the lung. Our goal was to
      determine if p-XSC but not Se-yeast is effective at inducing levels of
      glutathione (GSH)-related antioxidants and reducing markers of GSH oxidation in
      the NNK-induced lung tumor model. In the first bioassay, 6-week-old mice were fed
      either control or experimental diets (containing 10 ppm as selenium from p-XSC or
      Se-yeast) and, beginning at 8 weeks of age, received NNK (3 micromol) by gavage
      once weekly for 8 weeks. After 18 weeks, p-XSC significantly reduced NNK-induced
      tumor burden by 74% (10.4 +/- 6.0 versus 2.7 +/- 1.5 tumors/mouse, P < 0.001) and
      tumor incidence from 96% to 68% (P < 0.01), whereas, Se-yeast had no effect. Lung
      GSH levels were unchanged by either NNK or Se-yeast, but were increased 70% in
      mice treated with both NNK and p-XSC (P < 0.01) and 41% in mice treated with p
      XSC alone. In the second bioassay, the time course of effects of p-XSC was
      examined. As early as one week after initiation of p-XSC feeding lung and blood
      selenium levels were increased nearly six- and two-fold, respectively. Increases
      of 120% for GSH and 65% for Cys were observed in p-XSC groups compared to
      controls within one week after initiation of p-XSC feeding (P < 0.01). The levels
      of protein-bound:free GSH ratios and Cys ratios were significantly decreased in p
      XSC-treated mice, regardless of NNK status, suggesting a decrease in the levels
      of oxidative stress. Altogether, these results indicate that p-XSC is a potent
      inducer of GSH and related thiol antioxidants in the lung leading to decreased
      levels of oxidative stress and suggest that p-XSC inhibits tumor formation, in
      part, by protecting against oxidative damage.

PMID- 16620796
TI  - Bilayer phase transitions of N-methylated dioleoylphosphatidylethanolamines under
      high pressure.
AB  - The bilayer phase transitions of four kinds of unsaturated phospholipids with
      different-sized polar head groups, dioleoylphosphatidylethanolamine (DOPE),
      dioleoylphosphatidyl-N-methylethanolamine (DOMePE), dioleoylphosphatidyl-N,N
      dimethylethanolamine (DOMe2PE) and dioleoylphosphatidylcholine (DOPC), were
      observed by means of differential scanning calorimetry (DSC) and high-pressure
      light-transmittance. DSC thermogram and light-transmittance curve for each
      phospholipid vesicle solution exhibited only one phase transition under ambient
      pressure, respectively. The light-transmittance of DOPC solution at pressure
      higher than 234 MPa abruptly increased stepwise at two temperatures, which
      corresponds to the appearance of stable subgel and lamellar gel phases under high
      pressure in addition to the liquid crystal phase. The constructed temperature (T)
      pressure (p) phase diagrams were compared among these phospholipids. The phase
      transition temperatures of the phospholipids decreased stepwise by N-methylation
      of the head group. The slops of the T-p phase boundary (dT/dp) of DOPE, DOMePE
      and DOMe2PE bilayers (0.127-0.145 K MPa-1) were found to be close to that of the
      transition from the lamellar crystal (or subgel; Lc) phase to the liquid crystal
      (Lalpha) phase for DOPC bilayer (0.131 K MPa-1). On the other hand, the dT/dp
      value of the main transition from the lamellar gel (Lbeta) phase to the Lalpha
      phase for DOPC bilayer (0.233 K MPa-1) was significantly different from that of
      the Lc/Lalpha transition, hence both curves intersected with each other at 234
      MPa. The thermodynamic quantities associated with the phase transition of DOPE,
      DOMePE and DOMe2PE bilayers had also similar values to those for the Lc/Lalpha
      transition of DOPC bilayer. Taking into account of the values of transition
      temperature, dT/dp and thermodynamic quantities compared with the corresponding
      results of saturated phospholipids, we identified the phase transitions observed
      in the DOPE, DOMePE and DOMe2PE bilayers as the transition from the Lc phase to
      the Lalpha phase although they have been regarded as the main transition in the
      previous studies. The Lbeta phase is probably unstable for DOPE, DOMePE and
      DOMe2PE bilayers at all pressures, it exists as a metastable phase at pressures
      below 234 MPa while as a stable phase at pressures above 234 MPa in DOPC bilayer.
      The difference in phase stability among the phospholipid bilayers is originated
      from that in hydration structure of the polar head groups.

PMID- 16620797
TI  - Modelling of proteins in membranes.
AB  - This review describes some recent theories and simulations of mesoscopic and
      microscopic models of lipid membranes with embedded or attached proteins. We
      summarize results supporting our understanding of phenomena for which the
      activities of proteins in membranes are expected to be significantly affected by
      the lipid environment. Theoretical predictions are pointed out, and compared to
      experimental findings, if available. Among others, the following phenomena are
      discussed: interactions of interfacially adsorbed peptides, pore-forming
      amphipathic peptides, adsorption of charged proteins onto oppositely charged
      lipid membranes, lipid-induced tilting of proteins embedded in lipid bilayers,
      protein-induced bilayer deformations, protein insertion and assembly, and lipid
      controlled functioning of membrane proteins.

PMID- 16620798
TI  - Isothermal titration calorimetric study of calcium association to lipid bilayers:
      influence of the vesicle preparation and composition.
AB  - The association of Ca2+ ions with phospholipid bilayers was investigated using
      isothermal titration calorimetry. The study reveals that the binding enthalpy of
      these cations to bilayers formed with 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC), and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol
      (POPG) depends strongly on the method of preparation of the unilamellar vesicles.
      Extruded vesicles lead to an exothermic association, whereas sonicated ones lead
      to an endothermic association. In the later case, the calorimetric signal is
      sensitive to the length of the sonication period. It is proposed that a
      reorganization of the lipid bilayers under stress, obtained with sonicated small
      unilamellar vesicles, contributes to the calorimetric signal upon the titration
      with Ca2+. The analysis of the titrations indicates that, as expected, the nature
      of the association of Ca2+ with negatively charged phospholipid bilayers is
      essentially of electrostatic nature. Using a Scatchard approach, it is found that
      bilayers become saturated in Ca2+ approximately when the electroneutrality of the
      bilayer interface is reached. Moreover, the affinity constant was reduced by the
      increase of the ionic strength of the aqueous buffer. It was found that the
      intrinsic binding constant of Ca2+ to membranes containing 30 and 50 mol% of POPG
      was about 11 mM-1, in a MES buffer containing 10 mM NaCl, at pH 5.6.

PMID- 16620799
TI  - Micelle formation of bile salts and zwitterionic derivative as studied by two
      dimensional NMR spectroscopy.
AB  - The self-association of sodium taurodeoxycholate (NaTDC) and a zwitterionic
      derivative of cholic acid (CHAPS) in deuterium oxide was investigated by one- and
      two-dimensional nuclear magnetic resonance spectroscopy (NMR) spectroscopy.
      Analysis of the concentration dependence of the chemical shifts of several
      protons suggested that NaTDC and CHAPS form nonamers and heptamers, respectively,
      as well as dimer. The equilibrium constants of dimerization and the micellar
      aggregation numbers are close to the literature values. From the intensities of
      intermolecular cross-peaks in the nuclear Overhauser effect spectroscopy (NOESY)
      and rotating frame nuclear Overhauser effect spectroscopy (ROESY) spectra of
      NaTDC and CHAPS micellar solutions, partial structures of their micelles were
      estimated. The CHAPS micelle consists mainly of the back-to-back association,
      similarly to taurocholate (NaTC). However, the NaTDC micelle consists of the back
      to-face association, because the face of NaTDC is rather hydrophobic.
      Furthermore, the back of bile molecules forms a convex plane and the face forms a
      concave plane. The back-to-face structure of NaTDC will be stabilized by a close
      contact between these planes. The chemical shift changes of several protons of
      CHAPS and NaTC in the micellar state are close to each other, but are different
      from those of NaTDC. This finding is consistent with the difference in their
      micellar structures.

PMID- 16620800
TI  - Anchoring mechanisms of membrane-associated M13 major coat protein.
AB  - Bacteriophage M13 major coat protein is extensively used as a biophysical,
      biochemical, and molecular biology reference system for studying membrane
      proteins. The protein has several elements that control its position and
      orientation in a lipid bilayer. The N-terminus is dominated by the presence of
      negatively charged amino acid residues (Glu2, Asp4, and Asp5), which will always
      try to extend into the aqueous phase and therefore act as a hydrophilic anchor.
      The amphipathic and the hydrophobic transmembrane part contain the most important
      hydrophobic anchoring elements. In addition there are specific aromatic and
      charged amino acid residues in these domains (Phe 11, Tyr21, Tyr24, Trp26, Phe42,
      Phe45, Lys40, Lys43, and Lys44) that fine-tune the association of the protein to
      the lipid bilayer. The interfacial Tyr residues are important recognition
      elements for precise protein positioning, a function that cannot be performed
      optimally by residues with an aliphatic character. The Trp26 anchor is not very
      strong: depending on the context, the tryptophan residue may move in or out of
      the membrane. On the other hand, Lys residues and Phe residues at the C-terminus
      of the protein act in a unique concerted action to strongly anchor the protein in
      the lipid bilayer.

PMID- 16620801
TI  - Interaction of alcohols with serum LDL An infrared study.
AB  - The interaction of low molecular weight alcohols with low density lipoprotein
      (LDL) has been studied using amide I band-fitting, thermal profiling and two
      dimensional infrared correlation spectroscopy (2D-IR). At 0.3 M alcohol, no
      changes in secondary structure are observed. In the presence of 1 M alcohol,
      ethanol and propanol decreases protein denaturation temperature and produces
      changes in the amide I thermal profiles of protein components and in the lipid
      bands. The 2D-IR synchronous map corresponding to protein or lipid component at
      20-37 degrees C suggests differences in the presence of propanol. The
      asynchronous map corresponding to the lipid component indicates changes in
      bandwidth, compatible with a more fluid environment. In the 37-80 degrees C
      temperature range the thermal profile is different in the presence of propanol,
      both for the lipid and protein components. The results presented show that when
      alcohols affect the protein component, the lipid spectrum also varies pointing to
      an effect on the lipid-protein interaction.

PMID- 16620802
TI  - Using discordance to improve classification in narrative clinical databases: an
      application to community-acquired pneumonia.
AB  - Data mining in electronic medical records may facilitate clinical research, but
      much of the structured data may be miscoded, incomplete, or non-specific. The
      exploitation of narrative data using natural language processing may help,
      although nesting, varying granularity, and repetition remain challenges. In a
      study of community-acquired pneumonia using electronic records, these issues led
      to poor classification. Limiting queries to accurate, complete records led to
      vastly reduced, possibly biased samples. We exploited knowledge latent in the
      electronic records to improve classification. A similarity metric was used to
      cluster cases. We defined discordance as the degree to which cases within a
      cluster give different answers for some query that addresses a classification
      task of interest. Cases with higher discordance are more likely to be incorrectly
      classified, and can be reviewed manually to adjust the classification, improve
      the query, or estimate the likely accuracy of the query. In a study of pneumonia-
      in which the ICD9-CM coding was found to be very poor--the discordance measure
      was statistically significantly correlated with classification correctness (.45;
      95% CI .15-.62).

PMID- 16620803
TI  - A new method for quantitative analysis of dentinal tubules.
AB  - Conventional methods to estimate the number of dentinal tubules cannot be
      considered reliable and repeatable, because results depends on the operator
      outlining of the tubules contours. In this study, we propose a totally automated
      computerized analysis technique to evaluate dentinal tubules and their surface
      area. The comparison test of these conventional with a semi-automatic methods
      shows that the automated analysis allowed a reliable identification and numbering
      of dentinal tubules, by means of high-quality images. No statistically
      significant difference exists in the number of tubules and the total tubule
      surface area between the control and test groups.

PMID- 16620804
TI  - Modelling, property verification and behavioural equivalence of lactose operon
      regulation.
AB  - Understanding biochemical pathways is one of the biggest challenges in the field
      of molecular biology nowadays. Computer science can contribute in this area by
      providing formalisms and tools to simulate and analyse pathways. One formalism
      that is suited for modelling concurrent systems is Milner's Calculus of
      Communicating Systems (CCS). This paper shows the viability of using CCS to model
      and reason about biochemical networks. As a case study, we describe the
      regulation of lactose operon. After describing this operon formally using CCS, we
      validate our model by automatically checking some known properties for lactose
      regulation. Moreover, since biological systems tend to be very complex, we
      propose to use multiple descriptions of the same system at different levels of
      abstraction. The compatibility of these multiple views can be assured via
      mathematical proofs of observational equivalence.

PMID- 16620805
TI  - Computerized detection of breast masses in digitized mammograms.
AB  - We propose a system to detect malignant masses on mammograms. We investigated the
      behavior of an iris filter at different scales. After iris filter was applied,
      suspicious regions were segmented by means of an adaptive threshold. Suspected
      regions were characterized with features based on the iris filter output and,
      gray level, texture, contour-related, and morphological features extracted from
      the image. A backpropagation neural network classifier was trained to reduce the
      number of false positives. The system was developed and evaluated with two
      completely independent data sets. Results for a test set of 66 malignant and 49
      normal cases, evaluated with free-response receiver operating characteristic
      analysis, yielded a sensitivity of 88% and 94% at 1.02 false positives per image
      for lesion-based and case-based evaluation, respectively. Results suggest that
      the proposed method could help radiologists as a second reader in mammographic
      screening.

PMID- 16620806
TI  - Effects of rapid cooling on articular cartilage.
AB  - In order to improve the technique and protocols of cryopreservation of articular
      cartilage, a study was carried out to assess the effects of rapid cooling on the
      intact articular cartilage. Cartilage slices with a thickness ranging from 0.2 to
      0.5 mm taken from bovine metacarpal-phalangeal joints were subjected to rapid
      cooling by immersing them in liquid nitrogen with and without treatment of the
      VS55 cryoprotective agent (CPA). The ultrastructure, chondrocyte viability,
      swelling property, and glycosaminoglycan (GAG) content were then examined before
      and after cryopreservation to give qualitative and quantitative evaluation on the
      functional state of both chondrocytes and extracellular matrix. The transmission
      electron microscopy study demonstrated that damage to chondrocytes without CPA
      was far more pronounced than those with VS55 protection while the structure of
      the extracellular matrix altered little in either group. The cell viability assay
      showed that although the exposure to VS55 led to about 36% chondrocytes losing
      membrane integrity, the VS55 could provide protection to chondrocytes during
      rapid cooling and thawing, with approximately 51% of the cells having survived
      rapid cooling compared to fewer than 5% in the absence of CPA. There were no
      significant differences in degrees of swelling or the GAG contents of cartilage
      slices after cryopreservation indicating rapid freezing caused little damage to
      the matrix. Future research activities include searching improved CPA
      formulation, optimising the treatment protocol and investigating the long-term
      effects of rapid cooling on articular cartilage.

PMID- 16620807
TI  - Housing characteristics and indoor concentrations of nitrogen dioxide and
      formaldehyde in Quebec City, Canada.
AB  - Concentrations of nitrogen dioxide and formaldehyde were determined in a study of
      96 homes in Quebec City, Canada, between January and April 2005. In addition,
      relative humidity, temperature, and air change rates were measured in homes, and
      housing characteristics were documented through a questionnaire to occupants.
      Half of the homes had ventilation rates below 7.5 L/s person. Nitrogen dioxide
      (NO2) and formaldehyde concentrations ranged from 3.3 to 29.1 microg/m3
      (geometric mean 8.3 microg/m3) and from 9.6 to 90.0 microg/m3 (geometric mean of
      29.5 microg/m3), respectively. The housing characteristics documented in the
      study explained approximately half of the variance of NO2 and formaldehyde. NO2
      concentrations in homes were positively correlated with air change rates
      (indicating a significant contribution of outdoor sources to indoor levels) and
      were significantly elevated in homes equipped with gas stoves and, to a lesser
      extent, in homes with gas heating systems. Formaldehyde concentrations were
      negatively correlated with air change rates and were significantly elevated in
      homes heated by electrical systems, in those with new wooden or melamine
      furniture purchased in the previous 12 months, and in those where painting or
      varnishing had been done in the sampled room in the previous 12 months. Results
      did not indicate any significant contribution of indoor combustion sources,
      including wood-burning appliances, to indoor levels of formaldehyde. These
      results suggest that formaldehyde concentrations in Quebec City homes are caused
      primarily by off-gassing, and that increasing air change rates in homes could
      reduce exposure to this compound. More generally, our findings confirm the
      influence of housing characteristics on indoor concentrations of NO2 and
      formaldehyde.

PMID- 16620808
TI  - Influence of exposure to pesticides on serum components and enzyme activities of
      cytotoxicity among intensive agriculture farmers.
AB  - Although the effects of acute pesticide poisoning are well known for the
      pesticides most currently used, hardly any data exist on health effects after
      long-term low-dose exposures. Major unresolved issues include the effect of
      moderate exposure in the absence of poisoning. The increased utilization of
      pesticides other than organophosphates makes it even more difficult to find
      associations. In this study a cohort of 106 intensive agriculture workers were
      assessed twice during the course of a spraying season for changes in serum
      biochemistry, namely enzymes reflecting cytotoxicity (AST, ALT, LDH, CK, and
      amino-oxidase) and other biochemical parameters, such as markers of
      nephrotoxicity (urea, creatinine) and lipid profile (cholesterol and
      triglycerides). Several criteria for estimating pesticide exposure were used, the
      most important one being serum cholinesterase depression greater than 25% from
      baseline to peak exposure. Our results revealed an association of pesticide
      exposure with changes in AST (increased activity), LDH, and amino-oxidase
      (decreased activity) as well as with changes in serum creatinine and phosphorus
      (lower and higher levels, respectively). These results provide support for a very
      slight impairment of the liver function, but overall these findings are
      consistent with no clinically significant hepatotoxicity. Intriguingly,
      paraoxonase-1 R allele was found to be an independent predictor of higher rates
      of AST and lower rates of amino-oxidase, so that it may play a supporting role as
      an individual marker of susceptibility on pesticide-induced health effects. In
      conclusion, different biomarkers might be used to detect early biochemical
      effects of pesticides before adverse clinical health effects occur.

PMID- 16620809
TI  - Naegleria fowleri: a free-living highly pathogenic amoeba contains
      trypanothione/trypanothione reductase and glutathione/glutathione reductase
      systems.
AB  - This paper presents definitive data showing that the thiol-bimane compound
      isolated and purified by HPLC from Naegleria fowleri trophozoites unequivocally
      corresponds by matrix assisted laser-desorption ionization-time-of-flight MS, to
      the characteristic monoprotonated ion of trypanothione-(bimane)(2) [M(+)H(+)] of
      m/z 1104.57 and to the trypanothione-(bimane) of m/z 914.46. The trypanothione
      disulfide T(S)(2) was also found to have a molecular ion of m/z 723.37.
      Additionally HPLC demonstrated that thiol-bimane compounds corresponding to
      cysteine and glutathione were present in Naegleria. The ion patterns of the thiol
      bimane compounds prepared from commercial trypanothione standard, Entamoeba
      histolytica and Crithidia luciliae are identical to the Naegleria thiol-bimane
      compound. Partially purified extracts from N. fowleri showed the coexistence of
      glutathione and trypanothione reductases activities. There is not doubt that the
      thiol compound trypanothione, which was previously thought to occur only in
      Kinetoplastida, is also present in the human pathogens E. histolytica and N.
      fowleri, as well as in the non-pathogenic euglenozoan E. gracilis. The presence
      of the trypanothione/trypanothione reductase system in N. fowleri creates the
      possibility of using this enzyme as a new "drug target" for rationally designed
      drugs to eliminate the parasite, without affecting the human host.

PMID- 16620810
TI  - Trypanosoma brucei: a survey of pyrimidine transport activities.
AB  - Purine uptake has been studied in many protozoan parasites in the last few years,
      and several of the purine transporters have been cloned. In contrast, very little
      is known about the salvage of preformed pyrimidines by protozoa, and no
      pyrimidine transporters have been cloned, yet chemotherapy based on pyrimidine
      nucleobases and nucleosides has been as effective as purine antimetabolites in
      the treatment of infectious and neoplastic disease. Here, we surveyed the
      presence of pyrimidine transporters in Trypanosoma brucei brucei. We could not
      detect any mediated uptake of thymine, thymidine or cytidine, but identified a
      very high-affinity transporter for cytosine, designated C1, with a K(m) value of
      0.048+/-0.009 microM. We also confirmed the presence of the previously reported
      U1 uracil transporter and found it capable of mediating uridine uptake as well,
      with a K(m) of 33+/-5 microM. A higher-affinity U2 uridine transporter
      (K(m)=4.1+/-2.1 microM) was also identified, but efficiency of the C1 and U2
      mediated transport was low. Pyrimidine antimetabolites were tested as potential
      trypanocidal agents and only 5-fluorouracil was found to be effective. This drug
      was efficiently taken up by bloodstream forms of T. b. brucei.

PMID- 16620811
TI  - Trypanosoma cruzi: alteration in the lymphoid compartments following interruption
      of infection by early acute benznidazole therapy in mice.
AB  - Disability and mortality as consequence of Chagas disease is enormous in South
      America. Recently, the success of the trypanocidal treatment with benznidazole,
      the only available drug, has been associated with the host immune response. In
      the current study, the impact of benznidazole administration immediately after
      the experimental infection with Trypanosoma cruzi was evaluated in the main
      lymphocyte populations in lymphoid organs. Untreated mice displayed enlargement
      of spleen and lymph node related to the increased frequency of T and B
      lymphocytes, respectively. An intense thymus involution with the depletion of
      CD4(+)CD8(+) double-positive thymocytes also occurred. Benznidazole treatment led
      to a partial reversion of the spleen and lymph node enlargement related to
      changes in the frequency of lymphocyte subsets due to infection. Prevention of
      thymus involution was achieved, with the profile of thymocyte subsets similar to
      that of non-infected mice. The parasitic load at the onset of T. cruzi infection
      seems critical to trigger immune system activation.

PMID- 16620812
TI  - Leishmania species: evidence for transglutaminase activity and its role in
      parasite proliferation.
AB  - Albeit transglutaminase (TGase) activity has been reported to play crucial
      physiological roles in several organisms including parasites; however, there was
      no previous report(s) whether Leishmania parasites exhibit this activity. We
      demonstrate herein that TGase is functionally active in Leishmania parasites by
      using labeled polyamine that becomes conjugated into protein substrates. The
      parasite enzyme was about 2- to 4-fold more abundant in Old World species than in
      New World ones. In L. amazonensis, comparable TGase activity was found in both
      promastigotes and amastigotes. TGase activity in either parasite stage was
      optimal at the basic pH, but the enzyme in amastigote lysates was more stable at
      higher temperatures (37-55 degrees C) than that in promastigote lysates.
      Leishmania TGase differs from mouse macrophage (M Phi) TGase in two ways: (1) the
      parasite enzyme is Ca(2+)-independent, whereas the mammalian TGase depends on the
      cation for activity, and (2) major protein substrates for L. amazonensis TGase
      were found within the 50-75 kDa region, while those for the M Phi TGase were
      located within 37-50 kDa. The potential contribution of TGase-catalyzed reactions
      in promastigote proliferation was supported by findings that standard inhibitors
      of TGase [e.g., monodansylcadaverine (MDC), cystamine (CS), and iodoacetamide
      (IodoA)], but not didansylcadaverine (DDC), a close analogue of MDC, had a
      profound dose-dependent inhibition on parasite growth. Myo-inositol-1-phosphate
      synthase and leishmanolysin (gp63) were identified as possible endogenous
      substrates for L. amazonensis TGase, implying a role for TGase in parasite
      growth, development, and survival.

PMID- 16620813
TI  - Corticosterone is not correlated with nest departure in snowy owl chicks (Nyctea
      scandiaca).
AB  - Snowy owl chicks typically depart from nests at approximately 18 days of age, but
      3 weeks before taking their first flight. High concentrations of corticosterone
      have been implicated in behavioral changes in many species, leading us to assess
      corticosterone's role in chick nest departure. Corticosterone titers in free
      living chicks, however, do not predict this departure event. Baseline
      corticosterone concentrations decrease as chicks age. By 13 days, corticosterone
      concentrations are 50% of concentrations in 1-day-old chicks. Baseline
      concentrations, however, do not differ between departed and nest-bound chicks.
      Furthermore, corticosterone concentrations become significantly elevated 30min
      after collecting the baseline sample, indicating that chicks are able to mount a
      corticosterone response to handling. This stress-induced rise in corticosterone
      also did not differ between departed and nest-bound chicks. Brood sizes varied,
      possibly resulting in increased stress in chicks from larger broods. Although
      many chicks died before reaching departure age, brood sizes at time of nest
      departure ranged from 1 to 10 chicks. Brood size was not correlated with age of
      nest departure or individual corticosterone concentrations. These data indicate
      that it is unlikely that corticosterone plays a role in triggering nest departure
      in snowy owl chicks.

PMID- 16620814
TI  - Extremely high conservation in the untranslated region as well as the coding
      region of CNP mRNAs throughout elasmobranch species.
AB  - C-type natriuretic peptide (CNP) is a crucial osmoregulatory hormone in
      elasmobranchs, participating in salt secretion and drinking. In contrast to
      teleosts and tetrapods in which the NP family is composed of a group of
      structurally related peptides, we have shown that CNP is the sole NP in sharks.
      In the present study, CNP cDNAs were cloned from four species of batoids, another
      group of elasmobranchs. The cloned batoid CNP precursors contained a plausible
      mature peptide of 22 amino acid residues that is identical to most shark CNP-22s,
      but five successive amino acids were consistently deleted in the prosegment
      compared with shark precursors, supporting the diphyletic classification of
      sharks and rays. In addition, molecular phylogenetic trees of CNP precursors were
      consistent with a diphyletic interpretation. Except for the deletion, the
      nucleotide and deduced amino acid sequences of the CNP cDNAs are extremely well
      conserved among all elasmobranch species, even between sharks and rays.
      Surprisingly, high conservation is evident not only for the coding region, but
      also for the untranslated regions. It is most likely that the high conservation
      is due to the low nucleotide substitution rate in the elasmobranch genome, and
      high selection pressure. The 3'-untranslated region of the elasmobranch CNP cDNAs
      contained three to six repeats of the ATTTA motif that is associated with the
      regulation of mRNA stability and translation efficiency. Alternative
      polyadenylation sites were also found; the long 3'-untranslated region contains a
      core of ATTTA motifs while the short form has only one or no ATTTA motif,
      indicating that the post-transcriptional modification of mRNA is important for
      regulation of CNP synthesis. These characteristics in the 3'-untranslated region
      were conserved among all elasmobranch CNP cDNAs. Since CNP has been implicated as
      a fast-acting hormone to facilitate salt secretion from the rectal gland, the
      conserved 3'-untranslated region most likely contributes to rapid regulation of
      CNP synthesis in elasmobranchs in response to acute changes in internal and
      external environments.

PMID- 16620815
TI  - Molecular biology and physiology of the melanocortin system in fish: a review.
AB  - The melanocortin system consists of melanocortin peptides derived from the
      proopiomelanocortin gene (in particular adrenocorticotropic hormone, ACTH, and
      melanocyte-stimulating hormones, MSH) and five melanocortin receptor subtypes
      (MC1R-MC5R). Knowledge of the melanocortin system in fish is still limited, but
      information on the receptor part of the system is very rapidly growing. The
      melanocortin receptors (MCRs) have been recently cloned from several species of
      fish. The amino acid sequences appear remarkably well conserved. Pharmacological
      characterisation studies of the first identified piscine MCRs indicate that ACTH
      may be the original ligand for the MCRs, while the MSH peptides gained
      specialised functions in the course of evolution. Considering the tissue
      distribution of the MCRs, there are two distinctions between mammals and fish:
      where in mammals the MC4R is exclusively expressed in the central nervous system,
      in the fish species examined so far it is also peripherally expressed. It does
      however, alike the situation in mammals, likely play a key role in the central
      regulation of food intake and energy balance. Not only the MCRs, but also many
      other factors involved herewith, have been found in fish and roughly appear to
      function similarly as in mammals. The second difference is the distribution of
      the MC5R, which appears less widely expressed in fish than in mammals.
      Considering the available data it is predicted that, in mammals and fish alike,
      skin colouration is mediated via MC1R and steroidogenesis via MC2R. This review
      provides a short overview of the basic molecular characteristics, pharmacology,
      and tissue distribution of the MCRs in the fish investigated up to now, as well
      as their physiological role in the processes of skin colouration,
      steroidogenesis, and feeding behaviour.

PMID- 16620816
TI  - Early experience with linezolid for infections in orthopaedics.
AB  - In infections following orthopaedic surgery, isolated staphylococci are reported
      to be methicillin resistant (MRSA) in up to 50% of cases. Linezolid, the first in
      a new class of antibiotics, has excellent efficacy against gram positive
      organisms that are resistant to other therapies and is 100% orally bioavailable.
      We report early results of its use for the treatment of resistant infections in
      orthopaedic practice. Infections were characterised according to the UK
      Nosocomial Infections National Surveillance Service classification of surgical
      infections as superficial, deep or organ/space. Osteomyelitis, joint sepsis and
      deep infection involving orthopaedic implants were included into the final
      category. Outcome was recorded as clinical, microbiological and blood parameter
      cure or fail. Over the 12-month study period, 54 patients received linezolid
      therapy, 41% of these had significant co-morbidity that might affect their
      ability to fight infection. Sixty-seven percent of infections were in association
      with implanted metal work. The majority of patients were treated with vancomycin
      for a short period before linezolid was used as oral 'switch' therapy for longer
      term administration, allowing early discharge in all cases. MRSA was isolated in
      87% of the patients treated. The mean length of linezolid therapy was 39 days (2
      151). Clinical success was achieved in 90% of patients overall. Though there were
      no life-threatening complications, adverse event rates were significantly higher
      than those recorded in the literature, with 19% of patients needing to cease
      therapy. Linezolid offers an alternative to traditional treatments for resistant
      infections and can facilitate early discharge. Patients need to be monitored
      closely, particularly where long-term therapy is planned.

PMID- 16620817
TI  - Can CT determine the site of traumatic osteochondral defects in the paediatric
      knee?
AB  - Currently the ability of pre-operative CT imaging to determine the origin of
      traumatic osteochondral lesions (OCL) in the knee in children is yet to be
      established. The surgical approach to the knee will to some extent be determined
      by the origin of the lesion. It is important to directly determine the site of
      the lesion from pre-operative scanning both to facilitate surgery, to have a
      better cosmetic result for the patient and have a quicker rehabilitation period.
      In a tertiary referral centre, from May 2004 to April 2005, eight patients were
      diagnosed as having an OCL. The initial reporting was done by either a senior
      registrar or consultant paediatric radiologist. Those children that had an OCL
      underwent an arthroscopy or definitive open surgery. The exact site of the lesion
      was then determined and recorded in the operative notes. All the original pre
      operative CT scans were given to a senior paediatric radiologist. The consultant
      on this occasion had no access to operative findings, or original CT reports. CTs
      reported by the paediatric radiology department are only able to correctly
      identify the site of origin of the OCL 50% of the time. Recent MR scanning
      techniques have improved the visualization of OCL. We authors therefore feel that
      in the future MRI should be used to assess the paediatric knee when an acute OCL
      is suspected.

PMID- 16620818
TI  - Prosthesis survivorship and clinical outcome of the Austin Moore
      hemiarthroplasty: An 8-year mean follow-up of a consecutive series of 500
      patients.
AB  - The results of a consecutive series of 500 patients treated with Austin Moore
      hemiarthroplasty prosthesis are reported. The range of follow-up was from 5-12
      years and the mean was 8 years. Only 10 patients were lost to follow-up and 398
      (81%) patients died within the follow-up period. The mean age of the patient
      population was 82 years, and 85% were women. The cumulative survivorship of the
      prosthesis was calculated at 94% (95% CI 90-96%) at 5 years and 83% (95% CI 65
      94%) at 12 years. A total of 66 secondary operations of any type were required in
      46 (9%) patients. Revision of the Austin Moore prosthesis was performed in 23
      cases (5%). Of the long-term survivors contacted for follow-up, 66 (81%) had no
      pain or minimal pain, whilst 5 (6%) reported constant pain in the hip. The
      revision rates in our series were higher for younger patients, those from their
      own home and with good pre-fracture mobility and mental function. For the frail
      elderly with a displaced intracapsular fracture this prosthesis can still be
      recommended. This paper presents the largest consecutive series, with the longest
      follow-up, currently available.

PMID- 16620819
TI  - Percutaneous plating of lower limb long bone fractures.
AB  - We conducted a study on indirect reduction and percutaneous plating in the
      treatment of 22 cases (mean age 50.3, S.D. 18.5, range 18-88) of non-diaphyseal
      fractures of long bones of the lower limb mainly using the lateral tibial head
      buttress plate. All cases achieved radiological union and full weight bearing
      walking. No major malalignment resulted and only one Gustilo III-b compound
      fracture required bone grafting. None required revision surgery from problem with
      union. One case required revision in the early learning phase and another patient
      suffered wound complication from self-herbal application which required local
      flap surgery. The satisfactory functional results and the lack of soft tissue
      complications suggest that this method should be considered in metaphyseal
      fractures where intramedullary nails are not applicable.

PMID- 16620820
TI  - The prevalence and incidence of pressure ulcers in hospitalised patients in the
      Netherlands: a prospective inception cohort study.
AB  - BACKGROUND: Pressure ulcers frequently occur in hospitalised patients. The
      prevalence of pressure ulcers grade 2 or worse varies from 3% to 12% in
      hospitalised patients. Incidence figures are not frequently reported. While
      incidence and prevalence are both measures of disease frequency, they provide
      different perspectives on pressure ulcers. OBJECTIVES: To describe the incidence
      rate and prevalence of pressure ulcers in hospitalised patients. DESIGN:
      Prospective inception cohort study. SETTING: Two large hospitals, one general
      (530-beds) and one teaching (1042-beds), in The Netherlands. PARTICIPANTS: A non
      selected, though not strictly random, sample of 1536 patients was eligible for
      inclusion in the study. One thousand four hundred and thirty one patients (93.2%)
      consented to participate. Eventually, 1229 patients (80%) had a complete follow
      up. The sample consisted of patients admitted to the surgical, internal,
      neurological and geriatric wards for more than 5 days between January 1999 and
      June 2000. METHODS: Follow-up once a week until pressure ulcer occurrence,
      discharge or length of stay over 12 weeks. MAIN OUTCOME MEASURES: Occurrence of a
      pressure ulcer grade 2 or worse during admission to hospital, according to the
      classification of the European Pressure Ulcer Advisory Panel. RESULTS: One
      hundred and thirty four patients developed 172 pressure ulcers during follow-up.
      The overall weekly incidence rate was 0.06 per week (95% confidence interval 0.05
      0.07 per week). Highest rates were observed for surgical patients and lowest for
      geriatric and neurologic patients (0.08 and 0.02, respectively). The week
      specific prevalence varied between 12.8% and 20.3%. CONCLUSIONS: Among patients
      hospitalised for more than 5 days overall one may expect 6% per week to develop
      pressure ulcers. It would appear that any preventive measures can only be
      effective if taken timely. Accordingly, preventive measures should be considered
      early, because pressure ulcers were observed already within the first week of
      admission.

PMID- 16620821
TI  - Effects of self-efficacy, social support and knowledge on adherence to PEFR self
      monitoring among adults with asthma: a prospective repeated measures study.
AB  - BACKGROUND: Long-term adherence to self-monitoring of peak expiratory flow rate
      (PEFR) is essential for early detection of declining lung function in individuals
      with asthma. Psychosocial and cognitive factors can influence adherence to PEFR
      self-monitoring behaviors. OBJECTIVES: The specific aims of this prospective,
      repeated measures study were to: (1) determine the effects of asthma self
      efficacy, perceived satisfaction with social support and asthma knowledge on
      adherence to PEFR self-monitoring behavior; and (2) examine whether adherence to
      PEFR self-monitoring mediates the effects of psychosocial/cognitive factors on
      lung function and asthma symptoms in adults with asthma. DESIGN: Sixty-eight
      participants completed standardized questionnaires three times at baseline, 1
      month, and 3 months and kept the records of PEFR self-monitoring behaviors twice
      a day. Data were analyzed using multiple linear regressions. Adherence rates to
      PEFR self-monitoring were 93.5% and 74.9% at 1 and 3 month, representing those
      who remained in the study (n=39). Other participants withdrew from the study.
      FINDINGS: Both at 1 and 3 month, psychosocial/cognitive factors as a whole did
      not account for a significant variance in adherence to PEFR self-monitoring.
      Univariate analyses, however, indicated that baseline asthma self-efficacy and
      asthma knowledge at 1 month were significant independent predictors for adherence
      to PEFR self-monitoring at 3 month. CONCLUSION: Adherence to PEFR self-monitoring
      did not mediate the effects of asthma self-efficacy, perceived satisfaction with
      social support, and asthma knowledge on lung function and asthma symptoms. Lung
      function was low, but participants reported low asthma symptoms, both of which
      remained stable over time. Because of a small sample size and high attrition, the
      findings of the study need to be interpreted with caution. Given the importance
      of long-term adherence to self-management in asthma and other chronic illnesses,
      factors influencing adherence need to be further investigated to set a basis for
      future interventions.

PMID- 16620822
TI  - Entry of Trypanosoma brucei gambiense into microvascular endothelial cells of the
      human blood-brain barrier.
AB  - Using an in vitro model of the human blood-brain barrier consisting of human
      brain microvascular endothelial cells we recently demonstrated that Trypanosoma
      brucei gambiense bloodstream-forms efficiently cross these cells via a
      paracellular route while Trypanosoma brucei brucei crosses these cells poorly.
      Using a combination of techniques that include fluorescence activated cell
      sorting, confocal and electron microscopy, we now show that some T.b. gambiense
      blood stream form parasites have the capacity to enter human brain microvascular
      endothelial cells. The intracellular location of the trypanosomes was
      demonstrated in relation to the endothelial cell plasma membrane and to the actin
      cytoskeleton. These parasites may be a terminal stage within a lysosomal
      compartment or they may be viable trypanosomes that will be able to exit the
      brain microvascular endothelial cells. This process may provide an additional
      transcellular route by which the parasites cross the blood-brain barrier.

PMID- 16620823
TI  - Variation in infection parameters among populations within parasite species:
      intrinsic properties versus local factors.
AB  - Within any parasite species, variation among populations in standard infection
      parameters (prevalence, intensity and abundance) is an accepted fact. The
      proportion of hosts infected and the mean number of parasites per host are not
      fixed values across the entire geographic range of any parasite species. The
      question is whether this inter-population variation occurs within a narrow,
      species-specific range and is thus driven mainly by the biological features of
      the parasite, or whether it is substantial and unpredictable, leaving population
      parameters at the mercy of local conditions. Here, the repeatability of estimates
      of prevalence, intensity and abundance of infection was assessed across
      populations of the same parasite species, for 77 metazoan parasite species of
      Canadian freshwater fishes. Overall, parameter values from different populations
      of the same parasite species were more similar to each other and more different
      from those of other species, than expected by chance alone. Much of the variation
      in parameter values in the dataset was associated with differences between
      parasite species, rather than with differences among populations within species.
      This was particularly true for intensity and abundance of infection; in contrast,
      prevalence values, while somewhat repeatable among populations of the same
      species, still showed considerable variation. Among the higher taxa investigated
      (monogeneans, trematodes, cestodes, nematodes, acanthocephalans, copepods), there
      was no evidence that species of one taxon display intrinsically greater variation
      in population parameters than species of other taxa. Overall, the results suggest
      that intensity and abundance of infection are real species characters, though
      somewhat variable. This conclusion supports the view that the biological features
      of parasite species can potentially override local environmental conditions in
      driving parasite population dynamics.

PMID- 16620824
TI  - Molecular and cellular biology of helminth parasites IV.

PMID- 16620825
TI  - Contributions from Caenorhabditis elegans functional genetics to antiparasitic
      drug target identification and validation: nicotinic acetylcholine receptors, a
      case study.
AB  - Following the complete sequencing of the genome of the free-living nematode,
      Caenorhabditis elegans, in 1998, rapid advances have been made in assigning
      functions to many genes. Forward and reverse genetics have been used to identify
      novel components of synaptic transmission as well as determine the key components
      of antiparasitic drug targets. The nicotinic acetylcholine receptors (nAChRs) are
      prototypical ligand-gated ion channels. The functions of these transmembrane
      proteins and the roles of the different members of their extensive subunit
      families are increasingly well characterised. The simple nervous system of C.
      elegans possesses one of the largest nicotinic acetylcholine receptor gene
      families known for any organism and a combination of genetic, microarray,
      physiological and reporter gene expression studies have added greatly to our
      understanding of the components of nematode muscle and neuronal nAChR subtypes.
      Chemistry-to-gene screens have identified five subunits that are components of
      nAChRs sensitive to the antiparasitic drug, levamisole. A novel, validated target
      acting downstream of the levamisole-sensitive nAChR has also been identified in
      such screens. Physiology and molecular biology studies on nAChRs of parasitic
      nematodes have also identified levamisole-sensitive and insensitive subtypes and
      further subdivisions are under investigation.

PMID- 16620827
TI  - Thermoregulation in the life cycle of nematodes.
AB  - An unanswered question in the biology of many parasites is the mechanism by which
      environmental (or external) and intrinsic signals are integrated to determine the
      switch from one developmental stage to the next. This is particularly pertinent
      for nematode parasites, many of which have a free-living stage in the environment
      prior to infection of the mammalian host, or for parasites such as filarial
      nematodes, which utilise an insect vector for transmission. The environmental
      changes experienced by a parasite upon infection of a mammalian host are
      extremely complex and poorly understood. However, the ability of a parasite to
      sense its new environment must be intrinsically linked to its developmental
      programme, as progression of the life cycle is dependent upon the infection
      event. In this review, the relationship between temperature and development in
      filarial nematodes and in the free-living species Caenorhabditis elegans is
      summarised, with a focus on the role of heat shock factor and heat shock protein
      90 in the nematode life cycle.

PMID- 16620826
TI  - New weapons in the war on worms: identification of putative mechanisms of immune
      mediated expulsion of gastrointestinal nematodes.
AB  - Parasitic nematode infections of humans and livestock continue to impose a
      significant public health and economic burden worldwide. Murine models of
      intestinal nematode infection have proved to be relevant and tractable systems to
      define the cellular and molecular basis of how the host immune system regulates
      resistance and susceptibility to infection. While susceptibility to chronic
      infection is propagated by T helper cell type 1 cytokine responses (characterised
      by production of IL-12, IL-18 and interferon-gamma), immunity to intestinal
      dwelling adult nematode worms is critically dependent on a type 2 cytokine
      response (controlled by CD4+T helper type 2 cells that secrete the cytokines IL
      4, IL-5, IL-9 and IL-13). However, the immune effector mechanisms elicited by
      type 2 cytokines in the gut microenvironment that precipitate worm expulsion have
      remained elusive. This review focuses on new studies that implicate host
      intestinal epithelial cells as one of the dominant immune effector cells against
      this group of pathogens. Specifically, three recently identified type 2 cytokine
      dependent pathways that could offer insights into the mechanisms of expulsion of
      parasitic nematodes will be discussed: (i) the intelectins, a new family of
      galactose-binding lectins implicated in innate immunity, (ii) the resistin-like
      molecules, a family of small cysteine-rich proteins expressed by multiple cell
      types, and (iii) cytokine regulation of intestinal epithelial cell turnover.
      Identifying how the mammalian immune response fights gastrointestinal nematode
      infections is providing new insights into host protective immunity. Harnessing
      these discoveries, coupled with identifying what the targets of these responses
      are within parasitic nematodes, offers promise in the design of a new generation
      of anti-parasitic drugs and vaccines.

PMID- 16620828
TI  - Risk of mortality and cardiovascular disease associated with the ankle-brachial
      index: Systematic review.
AB  - OBJECTIVE: To determine the strength and consistency with which a low ankle
      brachial pressure index (ABI), measured in the general population, is associated
      with an increased risk of subsequent death and/or cardiovascular events. DESIGN:
      Systematic review. DATA SOURCES: Medline, Embase, reference lists and grey
      literature were searched; studies known to experts were also retrieved. MAIN
      OUTCOME MEASURES: All cause mortality, fatal and non-fatal coronary heart disease
      and stroke. REVIEW METHODS: Longitudinal studies in which participants were
      representative of the general population (all ages, either sex) and which used
      any standard method for measurement and calculation of the ABI. Studies in which
      participants were selected according to presence of pre-existing disease or were
      post intervention (e.g. angioplasty or peripheral arterial grafting) were
      excluded. RESULTS: 11 studies comprising 44,590 subjects from six different
      countries were included. Despite clinical heterogeneity between studies, the
      findings were remarkably consistent in demonstrating an increased risk of
      clinical cardiovascular disease associated with a low ABI. A low ABI (<0.9) was
      associated with an increased risk of subsequent all cause mortality (pooled RR
      1.60, 95% CI 1.32-1.95), cardiovascular mortality (pooled RR 1.96, 95% CI 1.46
      2.64), coronary heart disease (pooled RR 1.45, 95% CI 1.08-1.93) and stroke
      (pooled RR 1.35, 95% CI 1.10-1.65) after adjustment for age, sex, conventional
      cardiovascular risk factors and prevalent cardiovascular disease. CONCLUSIONS:
      The ABI may help to identify asymptomatic individuals in the general population
      who are at increased risk of subsequent cardiovascular events. Evaluation is now
      required of the potential of incorporating ABI measurement into cardiovascular
      prevention programmes.

PMID- 16620829
TI  - Atorvastatin prevents hypoxia-induced inhibition of endothelial nitric oxide
      synthase expression but does not affect heme oxygenase-1 in human microvascular
      endothelial cells.
AB  - Beneficial cardiovascular effects of statins, the inhibitors of 3-hydroxy-3
      methylglutaryl coenzyme A (HMG-CoA) reductase, are particularly assigned to the
      modulation of inflammation. Endothelial nitric oxide synthase (eNOS) and heme
      oxygenase-1 (HO-1) are listed among the crucial protective, anti-inflammatory
      genes in the vasculature. Here we show that atorvastatin at pharmacologically
      relevant concentration (0.1 microM) enhanced the expression of eNOS in human
      microvascular endothelial cells (HMEC-1). Moreover, atorvastatin prevented
      hypoxia-induced decrease in eNOS expression. However, in the same cells
      atorvastatin was ineffective in modulation of HO-1 protein level. Therefore, we
      suggest that the protective effect of statins at their pharmacological
      concentrations is not mediated by enhancement of HO-1 activity, but may involve
      eNOS.

PMID- 16620830
TI  - Augmented levels of CD44 in macrophages from atherosclerotic subjects: a possible
      IL-6-CD44 feedback loop?
AB  - The cell-adhesion molecule CD44 likely participates in atherosclerosis
      development. We have shown previously that pro-inflammatory cytokines affect CD44
      expression. Therefore, this work examined the role of elevated CD44 levels in
      human macrophages. Macrophages from human atherosclerotic subjects (n=15) showed
      elevated levels of CD44 transcript and protein (1.5-fold) compared to matched
      controls (n=15) (P=0.050 and 0.044, respectively). To test whether genetic
      factors influence CD44 expression, two single nucleotide polymorphisms in the
      CD44 gene were analyzed but these were not associated with coronary artery
      disease. We also examined the potential connection between plasma cytokine levels
      and CD44 expression. In atherosclerotic subjects, elevated CD44 expression
      correlates (P=0.012) with enhanced macrophage IL-6 secretion (3.13+/-2.5 pg/mL
      versus 0.32+/-0.16 pg/mL in controls, P=0.021). Additionally, CD44-deficient mice
      exhibit less circulating IL-6 than wild-type controls (9.8+/-0.7 pg/mL versus
      14.3+/-0.7 pg/mL; P=0.032). Furthermore, IL-6 augments CD44 expression in primary
      human macrophages after 24 h (P=0.038) and 48 h (P=0.015). Taken together, our
      data show an IL-6-CD44 feedback loop in macrophages. Such a positive feedback
      loop may aggravate atherosclerosis development.

PMID- 16620831
TI  - Decreased number of circulating CD34+KDR+ cells in asymptomatic subjects with
      preclinical atherosclerosis.
AB  - OBJECTIVES: To assess whether circulating endothelial progenitor cells (CEPCs)
      can be considered as a cardiovascular risk marker before event has occurred, that
      is less firmly established than in clinically overt atherosclerosis. METHODS:
      Number of CD34+KDR+ cell number per ml blood was measured by flow cytometry in 84
      untreated subjects without cardiovascular disease. Atherosclerotic plaque was
      detected by ultrasound in carotid, abdominal aortic and femoral sites and the
      number of sites affected by plaque among these three sites was counted as 0, 1, 2
      or 3. Additionally, intima-media thickness (IMT) was measured by computerized
      ultrasound imaging of both common carotid segments. RESULTS: CD34+KDR+ cell
      number decreased by 48, 29 or 30% in the presence of carotid, aortic or femoral
      plaque (p<0.001, 0.05, 0.05, respectively) as compared to the absence of plaque
      and by 70% in the presence of three sites affected with plaque as compared with 0
      site with plaque (p<0.01) but did not change with increasing IMT tertiles.
      Adjustment for Framingham risk score, that was also associated with decreased
      CD34+KDR+ cell number (p<0.001), made CD34+KDR+ cell number associations with
      plaque insignificant, except at the carotid site (p<0.01). CONCLUSIONS: Reduced
      CEPC number may participate to preclinical stage of atherosclerosis and provide
      additional information to traditional risk factors as regards global risk
      assessment.

PMID- 16620832
TI  - Infection with a periodontal pathogen increases mononuclear cell adhesion to
      human aortic endothelial cells.
AB  - BACKGROUND: As a link between periodontal infections and an increased risk for
      vascular disease has been demonstrated, we assessed the ability of the Gram
      negative periodontal pathogen Porphyromonas gingivalis to modulate properties of
      endothelial cells linked to inflammation and proatherogenic pathways. METHODS AND
      RESULTS: Primary human aortic endothelial cells (HAEC) were infected with either
      P. gingivalis strain 381 or its non-invasive fimbriae-deficient mutant, DPG3, and
      incubated with U-937 monocytes, or Jurkat T cells. P. gingivalis-infected HAEC
      demonstrated significantly increased adhesion of immune cells compared to non
      infected cells or those infected with DPG3. Heat-killed bacteria had no effect on
      mononuclear cell adhesion and P. gingivalis LPS had only a minimal effect. P.
      gingivalis infection significantly increased HAEC expression of VCAM-1, ICAM-1
      and E-selectin, and enhanced production of IL-6, IL-8 and MCP-1. CONCLUSION:
      These data demonstrate that live invasive P. gingivalis 381 elicits a pro
      atherogenic response in HAEC.

PMID- 16620833
TI  - LDL fractions assessed by anion-exchange high-performance liquid chromatography
      in patients with coronary artery disease.

PMID- 16620834
TI  - Coronary flow reserve is impaired in patients with slow coronary flow.
AB  - BACKGROUND: Slow coronary flow (SCF) in a normal coronary angiogram is a well
      recognized clinical entity, but its etiopathogenesis remains unclear. However,
      previous studies have suggested that microvascular abnormalities and endothelial
      dysfunction responsible for SCF. Accordingly, we hypothesized that SCF phenomenon
      may be a form, at least early phase, of atherosclerosis that involve both small
      vessels and epicardial coronary arteries, and therefore we investigated coronary
      flow reserve (CFR) reflecting coronary microvascular function in patients with
      SCF. METHODS: Twenty subjects with SCF and 15 control subjects with normal
      coronary flow were studied. Coronary flow was quantified according to TIMI frame
      count (TFC). Coronary diastolic peak flow velocities were measured at baseline
      and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to
      baseline diastolic peak velocities. RESULTS: Demographic features, coronary risk
      factors, echocardiographic measurements except diastolic function parameters, and
      biochemical measurements were similar between the groups. CFR values were
      significantly lower in subjects with SCF than in the control group (1.99+/-0.38
      versus 2.99+/-0.47, P<0.0001). In addition, TIMI frame count independently
      correlated with CFR. CONCLUSION: These findings suggest that CFR, which reflects
      coronary microvascular function, is impaired in patients with SCF, and corrected
      TFC well correlates with CFR.

PMID- 16620835
TI  - Serum osteoprotegerin is inversely associated with carotid plaque echogenicity in
      humans.
AB  - Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily
      involved in the regulation of bone metabolism and vascular calcification. High
      serum values of OPG are associated with cardiovascular disease in humans. The
      purpose was to investigate serum OPG levels in subclinical carotid
      atherosclerosis and the relation between OPG levels and plaque morphology. OPG
      levels were compared in 29 persons with echogenic carotid plaques, 30 persons
      with echolucent plaques and 41 persons without carotid plaques, all recruited
      from a population health study. Computerized assessment of plaque echogenicity
      was done by use of the gray scale median (GSM). Participants with echogenic
      carotid plaques had lower serum OPG level (1.23 ng/ml; 1.02-1.48) (geometric
      mean; 95% CI) than persons with echolucent plaques (1.76 ng/ml; 1.46-2.14) and
      those without plaques (1.89 ng/ml; 1.60-2.21). OPG and PTH were independently
      related to GSM. A significant trend for decrease in GSM across quartiles of OPG
      was found (p=0.003) which remained significant even after adjustment for PTH and
      smoking. The present study demonstrates lower serum OPG levels in persons with
      subclinical echogenic carotid plaques and identified an inverse relation between
      serum OPG and plaque echogenicity. The findings support the concept that OPG may
      play an important role in arterial calcification.

PMID- 16620836
TI  - Reduced perlecan expression and accumulation in human carotid atherosclerotic
      lesions.
AB  - Heparan sulfate in the extracellular matrix of the artery wall has been proposed
      to possess anti-atherogenic properties by interfering with lipoprotein retention,
      suppression of inflammation, and inhibition of smooth muscle cell growth.
      Previously, the amount of heparan sulfate in atherosclerotic lesions from humans
      and animals has been shown to be reduced but the identity or identities of the
      heparan sulfate molecules being down regulated in this disease are not known. In
      this study, atherosclerotic lesions were retrieved from 44 patients undergoing
      surgery for symptomatic carotid stenosis. Normal iliac arteries from organ donors
      were used as controls. Analysis of the specimens by gene microarray showed a
      selective reduction in perlecan gene expression, whereas, expression of the other
      heparan sulfate proteoglycans in the artery wall, agrin and collagen XVIII,
      remained unchanged. Expression of the large chondroitin sulfate proteoglycan,
      versican, also remained unchanged. Real-time PCR confirmed the decrease in
      perlecan gene expression and the unchanged expression of versican. The findings
      were supported by immunohistochemical analysis demonstrating a reduced
      accumulation of both perlecan core protein and heparan sulfate in carotid
      lesions. The study demonstrates a reduction of perlecan mRNA-expression and
      protein deposition in human atherosclerosis, which in part explains the low
      levels of heparan sulfate in this disease.

PMID- 16620838
TI  - Flexion and extension structural properties and strengths for male cervical spine
      segments.
AB  - New vehicle safety standards are designed to limit the amount of neck tension and
      extension seen by out-of-position motor vehicle occupants during airbag
      deployments. The criteria used to assess airbag injury risk are currently based
      on volunteer data and animal studies due to a lack of bending tolerance data for
      the adult cervical spine. This study provides quantitative data on the flexion
      extension bending properties and strength on the male cervical spine, and tests
      the hypothesis that the male is stronger than the female in pure bending. An
      additional objective is to determine if there are significant differences in
      stiffness and strength between the male upper and lower cervical spine. Pure
      moment flexibility and failure testing was conducted on 41 male spinal segments
      (O-C2, C4-C5, C6-C7) in a pure-moment test frame and the results were compared
      with a previous study of females. Failures were conducted at approximately 90 N
      m/s. In extension, the male upper cervical spine (O-C2) fails at a moment of 49.5
      (s.d. 17.6)N-m and at an angle of 42.4 degrees (s.d. 8.0 degrees). In flexion,
      the mean moment at failure is 39.0 (s.d. 6.3 degrees) N-m and an angle of 58.7
      degrees (s.d. 5.1 degrees). The difference in strength between flexion and
      extension is not statistically significant. The difference in the angles is
      statistically significant. The upper cervical spine was significantly stronger
      than the lower cervical spine in both flexion and extension. The male upper
      cervical spine was significantly stiffer than the female and significantly
      stronger than the female in flexion. Odontoid fractures were the most common
      injury produced in extension, suggesting a tensile mechanism due to tensile loads
      in the odontoid ligamentous complex.

PMID- 16620837
TI  - Relation between charge-based apolipoprotein B-containing lipoprotein
      subfractions and remnant-like particle cholesterol levels.
AB  - OBJECTIVE: Both mildly modified LDL subfraction that carries a more-negative
      electric charge and remnant-like particles (RLP) are closely related to
      triglyceride (TG) levels. We examined the relation between the RLP-cholesterol
      (C) level and charge-based apolipoprotein (apo) B-containing lipoprotein
      subfractions as determined by capillary isotachophoresis (cITP) in patients with
      hypercholesterolemia. METHODS AND RESULTS: cITP apo B lipoprotein subfractions
      were identified by analyzing plasma depleted of the related lipoproteins. While
      fast-migrating triglyceride-rich lipoprotein (fTRL) subfraction contained both
      chylomicrons and VLDL fraction, slow TRL (sTRL) only contained VLDL. cITP fLDL
      also contained VLDL fraction, i.e., beta-VLDL. Levels of cITP fTRL and sTRL were
      significantly correlated with serum levels of TG, RLP-C, apo C-II, and C-III.
      Levels of cITP sTRL were also correlated with apo E. Levels of cITP fLDL were
      positively correlated with not only LDL-C levels but also levels of TG, RLP-C,
      apo C-II, C-III, and E. CONCLUSION: cITP fast LDL correlated with RLP-C levels
      and modified the relation between RLP-C and TG levels.

PMID- 16620839
TI  - Urine profiling using capillary electrophoresis-mass spectrometry and
      multivariate data analysis.
AB  - This work presents the development of a general and fast method for metabolic
      profiling of urine, using capillary electrophoresis-electrospray ionisation mass
      spectrometry (CE-ESIMS) and multivariate data analysis (DA). Human urine samples
      collected before and after ingestion of paracetamol were analysed at acidic and
      basic CE conditions, using both positive and negative ESI-MS detection. Analysis
      of the entire resulting data set, with no prior knowledge of the target
      compounds, using pair-wise 'fuzzy' correlation and eigenvalue analysis enabled
      the samples to be discriminated between on the basis of blank urine and urine
      collected after drug intake. By generating two-dimensional loadings plots, it was
      also possible to identify the m/z values of the substances responsible for the
      differentiation between control and dosed samples.

PMID- 16620840
TI  - Electrostatic calculations and quantitative protein retention models for ion
      exchange chromatography.
AB  - A novel set of protein descriptors has been developed to increase the
      understanding of protein behavior on chromatographic media. The protein
      descriptors are pH-dependent and based on electrostatic and hydrophobic
      properties of mainly the surface of the proteins as revealed by their three
      dimensional structure. Interpretable and predictive quantitative structure
      property relationship (QSPR) models were then obtained for protein retention in
      ion exchange chromatography at different pH values. In most cases the calculated
      average surface potential could be directly related to retention times. Moreover,
      the high retention of human lactoferrin observed in cation exchange even at high
      pH values could be modeled by adding descriptors of the charge asymmetry.

PMID- 16620841
TI  - Comparison of possible arrangements of five identical columns in preparative
      chromatography.
AB  - Goal of the paper is to demonstrate how configuration of a certain number of
      identical HPLC columns influences on the effectiveness of the isolation of a
      target component. There are two extreme configurations: all the available columns
      are operated in parallel (provided there are enough pumps available) or all the
      columns are connected in series. Various combinations of columns connected
      parallel and in series are possible. Besides batch operation more sophisticated
      multicolumn arrangements allowing continuous separation are considered. In
      particular, in this work different configurations of five columns were examined.
      For illustration the separation of a binary mixture was considered. As the
      objective function the productivity of the less retained component has been used.
      A standard model capable to describe the propagation of chromatographic bands has
      been used to optimize the operating conditions for various possible multicolumn
      arrangements.

PMID- 16620842
TI  - High-performance liquid chromatographic separation of imidazolinone herbicide
      enantiomers and their methyl derivatives on polysaccharide-coated chiral
      stationary phases.
AB  - Many chiral pesticides exhibit enantioselectivity in biotransformation and
      ecotoxicity in the environment. A significant class of chiral pesticides is
      imidazolinone herbicides, of which enantioselectivity has not been well studied.
      Development of efficient chiral separation methods is the first step for allowing
      characterization of enantioselectivity in environmental processes. In this study,
      we attempted to resolve enantiomers of imidazolinone herbicides using reversed
      phase and normal-phase high-performance liquid chromatography with polysaccharide
      type chiral columns. Enantiomers of imazethapyr, imazaquin, and imazamox were
      separated on a Chiralcel OD-R column using 50mM phosphate buffer-acetonitrile as
      mobile phase. Enantiomers of imazapyr, imazapic, imazethapyr, imazamox and
      imazaquin were resolved on a Chiralcel OJ column using n-hexane (0.1%
      trifluoroacetic acid)-alcohol as mobile phase. The enantiomers of five methyl
      derivatives of imidazolinone herbicides were also resolved on the Chiralcel OJ
      column. The Deltak' values revealed a structure-enantioselectivity relationship
      for the separation behaviors of the enantiomers on the OJ column. The described
      method was successfully applied for chiral analysis of two imidazolinone
      herbicides (imazapyr and imazaquin) in spiked soil samples.

PMID- 16620843
TI  - Application of high-speed counter-current chromatography coupled with high
      performance liquid chromatography-diode array detection for the preparative
      isolation and purification of hyperoside from Hypericum perforatum with online
      purity monitoring.
AB  - Following preparative isolation and purification by high-speed counter-current
      chromatography (HSCCC), the collected fractions were generally analyzed by high
      performance liquid chromatography (HPLC) to determine the relative purities of
      each fraction. Our paper reports for the first time a preparative isolation
      purity detection hyphenated system: online coupling of HSCCC with high
      performance liquid chromatography-diode array detection (HSCCC-HPLC-DAD). The
      introduction of online purity analysis in HSCCC has dramatically improved the
      efficiency of this technique by overcoming the drawbacks of post analysis in
      HSCCC isolation. The effluent from the outlet of HSCCC was splitted into two
      parts: one was collected, while the other was introduced directly into an HPLC
      DAD system for purity analysis through a switch valve. Therefore, the purities of
      the obtained fractions from HSCCC were monitored, and fractions with high
      purities were collected. This strategy has been successfully demonstrated with
      the preparative isolation and purification of hyperoside from Hypericum
      perforatum (St. Jone's Wort); a model of TBE-300A HSCCC was used to isolate and
      separate hyperoside from H. perforatum with a two-phase solvent system composed
      of ethyl acetate-ethanol-water at the volume ratio of 5:1:5 (v/v) using online
      detection technique. The isolation was done in less than 3.5 h, and a total of
      83.0-mg hyperoside at over 99.0% purity was yielded from 300 mg of the partially
      purified extract. This new strategy possesses general utility in the preparation
      of bioactive compounds from traditional Chinese medicine (TCM).

PMID- 16620845
TI  - On-line preconcentration of protein in capillary electrophoresis with an end
      column cellulose acetate-based porous membrane.
AB  - A simple on-line preconcentration method of protein for capillary electrophoresis
      (CE) using a cellulose acetate (CA)-coated porous membrane was proposed. CA
      membrane is fabricated at one of the ends of the column that allows the passage
      of buffer ions but excludes larger protein molecules. Protein sample is
      continuously electrokinetically loaded and trapped by the membrane. When
      injection is completed, the direction of the electric field is switched and the
      trapped proteins are then separated by conventional CE procedure. The results
      achieved showed that the preconcentration mechanism of this method was based on
      size-exclusion effect. Bovine serum albumin (BSA) was used for model protein
      sample, and signal enhancement of 550-fold with 15 min injection time was
      achieved.

PMID- 16620846
TI  - Analysis of polycyclic aromatic hydrocarbons in pine needles by gas
      chromatography-mass spectrometry: comparison of different extraction and clean-up
      procedures.
AB  - Three extraction methodologies (Soxhlet, ultrasonic and pressurized liquid
      extraction) and several clean-up procedures (Florisil, silica and alumina in
      cartridges or glass column format) were tested and compared to extract 16 US
      Environmental Protection Agency (EPA) polycyclic aromatic hydrocarbons (PAHs)
      from Pinus pinea L. needles. Quantification was done by gas chromatography with
      mass spectrometry, by internal standard method using five deuterated PAH
      surrogate standards. Among the several extraction and clean-up procedures tested,
      ultrasonic extraction followed by alumina cartridge clean-up was the preferred
      method, yielding recoveries between 72 and 100% and limits of detection between
      0.22 and 0.71 ng/g dry weight. The performance of the method was tested to
      determine PAHs in naturally contaminated samples.

PMID- 16620847
TI  - Comparison of micro-scale simultaneous distillation-extraction and stir bar
      sorptive extraction for the determination of volatile organic constituents of
      grape juice.
AB  - Traditional micro-scale simultaneous distillation-extraction (SDE) and stir bar
      sorptive extraction (SBSE) were compared for their effectiveness in the
      extraction of volatile organic compounds in a synthetic grape juice and a real
      grape juice (Huxelrebe, a variety of half Muscat ancestry) from an English
      vineyard. The novel immersion-mode SBSE method, using stir bars with PDMS
      sorbent, was optimised using the synthetic grape juice. Although mean percent
      relative recoveries and reproducibilities (%CV) of the SBSE method were inferior
      to SDE (28.4 and 8.5%, respectively, against 86.9 and 6.3%), the former method
      proved to be significantly more sensitive: 126 aroma compounds in Huxelrebe grape
      juice were identified using SBSE, against 98 using SDE. This allowed the
      identification of a number of volatile components that have not been reported
      previously in the juice or wine from the grapes of Muscat varieties.

PMID- 16620848
TI  - Sorption study of 25 volatile organic compounds in several Mediterranean soils
      using headspace-gas chromatography-mass spectrometry.
AB  - A sorption study of 25 volatile organic compounds (VOCs) in different
      agricultural soils was carried out by using headspace-gas chromatography-mass
      spectrometry. The extraction of the VOCs from soil samples was carried out
      following the EPA method with some differences such as addition of potassium
      chloride and different instrumental conditions which provide higher sample
      throughput. In addition, a complementary study on several procedures for soil
      fortification with VOCs was also assayed, fortification with minimal sample
      handling was selected in order to minimise evaporation losses of the VOCs. The
      effect of clay minerals (7.0-69.7%) and organic carbon (0.2-3.5%) contents on
      acid and alkaline (pH 5.3-8.8) soils were evaluated. Based on the results, all
      compounds assayed were more sorbed in alkaline soils than acid ones;
      chlorobenzenes interact more strongly with agricultural soils than do
      alkylbenzenes. The organic carbon content affects the sorption of 25 VOCs in
      alkaline soils (the highest sorption was found for the most organic soil), while
      in acid soils VOC sorption increases as the organic carbon content decreases. The
      clay mineral fraction plays an important role in the sorption of VOCs in acid
      soil owing to pi-/n-electron interactions, this effect being more marked for
      chlorobenzenes.

PMID- 16620849
TI  - Novel multi-depth microfluidic chip for single cell analysis.
AB  - A novel multi-depth microfluidic chip was fabricated on glass substrate by use of
      conventional lithography and three-step etching technology. The sampling channel
      on the microchip was 37 microm deep, while the separation channel was 12 microm
      deep. A 1mm long weir was constructed in the separation channel, 300 microm down
      the channel crossing. The channel at the weir section was 6 microm deep. By using
      the multi-depth microfluidic chip, human carcinoma cells, which easily aggregate,
      settle and adhere to the surface of the channel, can be driven from the sample
      reservoir to the sample waste reservoir by hydrostatic pressure generated by the
      difference of liquid level between sample and sample waste reservoirs. Single
      cell loading into the separation channel was achieved by applying a set of
      pinching potentials at the four reservoirs. The loaded cell was stopped by the
      weir and precisely positioned within the separation channel. The trapped cell was
      lysed by sodium dodecyl sulfate (SDS) containing buffer solution in 20s. This
      approach reduced the lysing time and improved the reproducibility of chip-based
      electrophoresis separations. Reduced glutathione (GSH) and reactive oxygen
      species (ROS) were used as model intracellular components in single human
      carcinoma cells, and the constituents were separated by chip-based
      electrophoresis and detected by laser-induced fluorescence (LIF). A throughput of
      15 samples/h, a migration time precision of 3.1% RSD for ROS and 4.9% RSD for GSH
      were obtained for 10 consecutively injected cells.

PMID- 16620850
TI  - On the determination of underivatised fatty alcohol ethoxylates by electrospray
      ionisation-mass spectrometry.
AB  - The oligomers of fatty alcohol ethoxylates (FAEs) exhibit large sensitivity
      differences in mass spectrometry with electrospray ionisation (ESI-MS) and
      atmospheric pressure chemical ionization (APCI). Standards of the oligomers from
      m=1 to 7 ethylene oxide units (EOs) and linear alkyl chains from n=10 to 18
      carbon atoms were infused to examine the relative sensitivities or response
      factors in several media. The response factors of the [M+H]+ and [M+Na]+ peaks in
      9:1 acetonitrile/water and methanol/water media containing acid buffers increased
      following irregular patterns when n and m increased. In methanol/water the
      response factors depended on the parity of m, being larger than the average trend
      for the oligomers with an even value of m with respect to those having an odd
      value. This was attributed to the presence of an uncompensated C-O-C or C-O-H
      dipole in the former oligomers. The advantages of using ESI over APCI and of
      measuring the [M+H]+ peaks in an acid methanol/water medium containing 0.1 M HCl
      are discussed. The advantages and limitations of using models of the response
      factors to evaluate oligomer concentrations with a reduced set of selected
      standards are examined. The determination of underivatised FAEs using acid media
      was made compatible with previous HPLC separation by implementing either a
      triconcentric nebulizer fed with an acid liquid sheath, or a capillary T-union
      inserted between the column outlet and the biconcentric nebulizer, and fed with
      an acid stream provided by a syringe pump.

PMID- 16620851
TI  - Nuclease P1 digestion/high-performance liquid chromatography, a practical method
      for DNA quantitation.
AB  - We have developed a practical method for quantifying DNA. The method is practical
      in two ways. First, a single enzyme is used to digest the DNA to nucleotides that
      are then quantified by HPLC under ordinary conditions. Second, the method
      quantifies DNA even when it is impure. In our method, "nuclease P1/HPLC," the DNA
      is hydrolyzed by nuclease P1 and the resulting 2'-deoxynucleoside 5'
      monophosphates are quantified by HPLC with UV detection. This method was applied
      to several kinds of genomic DNA in terms of origin and method by which it had
      been purified. Calf thymus DNA (purified by salt precipitation by the supplier),
      pig liver DNA (purified by phenolic extraction or by anion-exchange
      chromatography using a Genomic Tip from Qiagen) and mouse skin DNA (similarly
      purified) were tested. In some cases a given sample was purified by two of these
      methods. The values for the amount of DNA by our method were compared with those
      by three other methods: acid hydrolysis/HPLC (selected as a reference procedure),
      UV absorbance, and dye binding. Agreement for all DNA samples between the values
      by our method versus those provided by acid hydrolysis/HPLC was within 10% for
      amounts of DNA in the 19-54 microg range. In contrast, UV absorbance and the dye
      binding assay gave differences up to 30-40% relative to the consistent values
      furnished by acid hydrolysis and our method. Overall, normalizing the
      concentrations of the DNA (thymus, liver, skin) by acid hydrolysis/HPLC in 10
      samples to values of 1.0 gave the following, relative values and standard
      deviations: 1.01+/-.07 (nuclease P1/HPLC), 0.8+/-0.17 (dye binding), and 1.1+/
      0.1 (UV). Since one cannot assume that any sample of DNA is pure, and determining
      purity of DNA is difficult, then nuclease P1/HPLC or acid hydrolysis/HPLC is
      recommended rather than the UV absorbance or dye binding for quantifying DNA
      whenever an accurate value is important.

PMID- 16620852
TI  - Rapid tool for distinction of wines based on the global volatile signature.
AB  - This work describes a novel methodology for the rapid distinction of wines by
      headspace solid-phase microextraction coupled to gas chromatography-mass
      spectrometry, followed by principal component analysis of the data (HS-SPME-GC-MS
      PCA). Headspace SPME is used to extract and concentrate the volatile and semi
      volatile fractions. A DB-FFAP fused silica GC capillary column of 30 m at 220
      degrees C was used acting as a transfer line of the components sorbed by the
      Carbowax-divinylbenzene coating fibre to the mass spectrometer, which acts as a
      sensor (30<m/z<300). In this methodology, which does not require any pre
      treatment of the sample, the global volatile signature of the wine headspace
      (chromatographic profile and m/z pattern of fragmentation in each scan) is
      evaluated without complete chromatographic separation of its components. In order
      to retrieve from the data as much chemical information as possible and to extract
      m/z fragments (markers) for the characterisation and distinction of the wines
      varieties, a PCA was applied to the data resultant from the unresolved volatile
      fraction. In the present study, two different monovarietal white wines (Vitis
      vinifera L. var. Fernao-Pires and Arinto) were tested. Associated to the fast
      character of the proposed methodology and robustness taking into account the
      extraction time, it is also important to focus the higher sensibility and the
      lower effect of the sample moisture of the MS sensor response when compared to
      the conventional e-noses.

PMID- 16620853
TI  - Phenylaminopropyl silica monolithic column for pressure assisted capillary
      electrochromatography.
AB  - A novel stationary phase phenylaminopropyl silica (PhA-silica) monolith was
      successfully prepared for pressure assisted capillary electrochromatography
      (pCEC). The monolithic silica matrix from a sol-gel process was chemically
      modified by using [3-(phenylamino)propyl]trimethoxysilane as surface modification
      reagent to produce the phenylaminoporpyl function. The secondary amino groups on
      the surface of the monolithic stationary phase contributed to the generation of
      anodic electroosmotic flow (EOF) under acidic conditions. The phenyl group
      together with the spacer (-(CH(2))(3)-) in PhA-silica provides sufficient
      hydrophobic properties. To evaluate the column performance, effects of buffer pH
      and mobile phase composition on the mobile phase linear velocity and the
      retention factors of alkylbenzenes, phenols and anilines were investigated in
      pCEC mode. The monolithic stationary phases exhibit typical reversed-phase (RP)
      electrochromatographic behavior toward neutral solutes. Hydrophobic as well as
      electrophoretic migration process within the monoliths was observed for the
      separation of basic solutes such as anilines without peak tailing.

PMID- 16620854
TI  - Isolation of human serum immunoglobulins with a new salt-promoted adsorbent.
AB  - In this work a highly acetylated-ethylenediamine-Novarose (HA-EDA-Novarose) gel
      was synthesized and used as a new agarose-based salt-promoted adsorption
      chromatography (SPAC) matrix to effectively isolate serum immunoglobulins without
      the need of denaturing conditions. Samples of human serum in 0.5 M Na2SO4, 10 mM
      3-(N-morpholino)-propane-sulfonic acid (MOPS), pH 7.6 were applied to a
      chromatographic column packed with the SPAC gel. Immunoglobulins (Igs) with
      affinity for the HA-EDA ligands were specifically adsorbed to the matrix, non
      bound serum proteins were readily removed by washing the column with the same
      feed solution buffer. Bound Igs were effectively and very gently eluted by simply
      removing the salt from the feed solution buffer. The elution buffer consisted
      thus of only 10 mM MOPS, at pH 7.6 and no salt. The salt-dependent adsorption
      capacity of this system was estimated to be 7.3 mg/ml with protein recovery of
      about 93%. Sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE) electrophoresis
      analysis, radial immunodiffusion and enzyme-linked immunosorbent assays showed
      that immunoglobulins G, M and A (IgG, IgM and IgA) were the main components
      present in the elution fraction. The new SPAC adsorbent was used to purify Igs
      from human serum and IgG and IgA from non-pure commercially available Igs
      preparations in a very gentle single step.

PMID- 16620855
TI  - Separation of phospholipids by capillary zone electrophoresis with indirect
      ultraviolet detection.
AB  - A simple method for separation of different anionic and zwitterionic phospholipid
      classes by capillary zone electrophoresis (CZE), using indirect UV detection with
      adenosine monophosphate (AMP) as background electrolyte and the UV-absorbing
      additive, was successfully developed in this study. The separation conditions
      including apparent pH (pH*) of running buffer, concentration of AMP, organic
      solvent, applied voltage and capillary temperature were systematically optimized.
      The application of this method to human blood sample was also briefly examined.

PMID- 16620856
TI  - Development of dinitrophenylated cyclodextrin derivatives for enhanced
      enantiomeric separations by high-performance liquid chromatography.
AB  - The synthesis and evaluation of new dinitrophenyl (DNP) substituted beta
      cyclodextrin (beta-CD) chiral stationary phases (CSPs) for the enantioseparation
      of various classes of chiral analytes by HPLC are presented. The dinitrophenyl
      substituted beta-CD derivatives are synthesized and covalently bonded to
      functionalized 5 microm spherical porous silica gel. These are the first reported
      derivatized cyclodextrin which contains pi-electron deficient substituents (i.e.,
      pi-acidic moieties). The column performance in terms of their ability to separate
      enantiomers is evaluated. A variety of different dinitro-substituted aryl groups
      are investigated and compared. The pH of the mobile phase buffers, the buffer
      composition, the number and position of the dinitro groups on the phenyl ring
      substituent, the degree of substitution, and the bonding strategy all greatly
      affect the performance of the CSPs. A large variety of racemic compounds have
      been separated successfully on these CSPs. The bonded dinitrophenyl-derivatized
      cyclodextrins are stable in all three mobile phase modes, namely, the reversed
      phase, polar organic, and normal phase modes. No degradation in column
      performance was observed in any mode of operation even after more than 1000
      injections. The analytical applicability of these types of CSPs for enantiomeric
      separations is discussed in detail.

PMID- 16620857
TI  - Determination of total dissolved inorganic carbon in freshwaters by reagent-free
      ion chromatography.
AB  - Studies of inorganic carbon cycle in natural waters provide important information
      on the biological productivity and buffer capacity. Determination of total
      inorganic carbon, alkalinity and dissolved carbon dioxide gives an indication of
      the balance between photosynthesis and respiration by biota, both within the
      water column and sediments, and carbon dioxide transfers from the water column to
      the atmosphere. There are few methods to measure and distinguish the different
      forms of inorganic carbon, but all require a measure or an indirect
      quantification of total inorganic carbon. A direct measurement of TIC in water is
      made possible by the introduction of electrolytic generated hydroxide eluent in
      ion chromatography which allows to detect a chromatographic peak for carbonate.
      The advantage of this method is that all the inorganic forms of carbon are
      converted in carbonate at eluent pH and can be detected as a single peak by
      conductivity detection. Repeatability of carbonate peak was evaluated at
      different levels from 0.02 to 6 mequiv.l(-1) both in high purity water and in
      real samples and ranged from 1 to 9%. The calibration curve was not linear and
      has to be fitted by a quadratic curve. Limit of detection was estimated to be
      0.02 mequiv.l(-1). Accuracy has been estimated by comparing ion chromatography
      method with total inorganic carbon calculated from alkalinity and pH. The
      correlation between the two methods was good (R(2)=0.978, n=141). The IC method
      has been applied to different typologies of surface waters (alpine and subalpine
      lakes and rivers) characterised by different chemical characteristics (alkalinity
      from 0.05 to 2 mequiv.l(-1) and pH from 6.7 to 8.5) and low total organic carbon
      concentrations. This analytical method allowed to describe the distribution of
      TIC along the water column of two Italian deep lakes.

PMID- 16620858
TI  - On-line desalting-mass spectrometry system for the structural determination of
      hydrophilic metabolites, using a column switching technique and a volatile ion
      pairing reagent.
AB  - A novel desalting method, using a column switching technique and a volatile ion
      pairing reagent, pentadecafluorooctanoic acid, was developed. This system allows
      hydrophilic and cationic compounds in a nonvolatile buffer to be directly
      introduced into a mass spectrometer for structural elucidation. The desalting
      procedure consists of four steps: (1) the fractionation of a target compound from
      a separation column, (2) the removal of salts with pentadecafluorooctanoic acid
      on the trap column, (3) the desorption of the compound from the trap column, and
      (4) the re-equilibration of the trap column with a pentadecafluorooctanoic acid
      solution. In this procedure, we investigated the methods for optimizing the
      desalting and re-equilibration steps. Various amino acids, including branched
      chain amino acids, aromatic amino acids, basic amino acids and methionine, after
      separation with phosphate buffer on a cation-exchange column, were successively
      desalted by this method, and were observed as protonated ions by mass
      spectrometry. This desalting system could be useful for the structural
      elucidation of unknown hydrophilic compounds eluted by conventional high
      performance liquid chromatography methods, such as ion-exchange chromatography,
      with mobile phases containing nonvolatile salts. As an example, we present the
      structural elucidation of unknown metabolites in bovine serum.

PMID- 16620859
TI  - Determination of volatile flavor components in danggui cultivars by solvent free
      injection and hydrodistillation followed by gas chromatographic-mass
      spectrometric analysis.
AB  - The rhizome of Angelica gigas Nakai, Angelica sinensis Diels and Angelica
      acutiloba Kitagawa (Umbelliferae) were chopped and extracted by hydrodistillation
      (HD) and solvent free solid injector (SFSI) methods to obtain the volatile
      compounds that were then characterized and identified by gas chromatography-mass
      spectrometry (GC/MS). SFSI extraction yielded a generally higher amount of
      volatile compounds than that produced by HD. A total of 48 components [including
      terpenes (8), aldehydes (4), alcohol (2), coumarins (9), Phthalide (3), acids (2)
      and sterols (2)] were identified by SFSI and gas chromatography-mass spectrometry
      from the three species of danggui cultivars, whereas, 24-essential oil was
      obtained by HD for Korean danggui only. According to these analyses, several
      coumarin derivatives such as decursinol angelate (16.83%) and decursin (29.34%)
      were found to be the dominant ones, followed by lomatin (10.25%) and marmesin
      (9.33%) in Korean danggui. Furfural and butylidene phthalide were the main
      components in Japanese in addition to butylidene dihydro-phthalide in Chinese
      danggui. Some parameters affecting the extraction efficiency such as injector
      temperature, injection time and pre-heating time were optimized. The results
      showed that the SFSI-method gave a higher yield of components with higher
      molecular mass than hydrodistillation. SFSI required little time to prepare the
      sample, little sample mass and a small quantity of organic solvent was needed. It
      can be concluded that analysis of volatile flavor compounds by SFSI in
      combination with gas chromatography/mass spectrometry is a suitable monitoring
      technique to differentiate danggui cultivars.

PMID- 16620860
TI  - Visualising the onset of viscous fingering in chromatography columns.
AB  - Viscous fingering is an important fluid transport phenomenon that manifests
      itself when two fluids having different viscosities move in the same direction.
      Their interface is unstable and a complex fingering pattern may arise. This
      phenomenon is important in chromatography because it may lead to a decrease or
      even a failure in separations. The onset of viscous fingering was visually
      observed by packing a glass column with particles having the same refractive
      index as the mobile phase and injecting plugs of dye solutions having viscosities
      different from that of the mobile phase. Severe fingering effects are observed if
      the viscosity difference exceeds 0.17 cP. However, for smaller viscosity
      differences, band distortions are observed that may affect retention data, band
      efficiency, and band resolution. Careful attention should be paid to matching the
      mobile phase viscosity and that of the injection plug when accurate
      chromatographic information is required.

PMID- 16620861
TI  - Large-scale separation of alkaloids from Corydalis decumbens by pH-zone-refining
      counter-current chromatography.
AB  - pH-zone-refining counter-current chromatography was successfully applied to the
      separation of alkaloids from a crude extract of Corydalis decumbens (Thunb.)
      Pers. using a multilayer coil planet centrifuge (CPC). The experiment was
      performed with a two-phase solvent system composed of methyl tert-butyl ether
      (MtBE)-acetonitrile-water (2:2:3, v/v) where triethylamine (5-10 mM) was added to
      the upper organic stationary phase as a retainer and hydrochloric acid (5-10 mM)
      to the aqueous mobile phase as an eluter. From 3.1 g of the crude extract, 495 mg
      protopine, 626 mg tetrahydropalmatine and 423 mg bicuculline were obtained each
      with a purity of over 93% as determined by high performance liquid
      chromatography. The structures of the isolated compounds were identified by
      electron ionization mass spectrometry (EI-MS), high-performance liquid
      chromatography (HPLC)-electrospray ionisation-mass spectrometry (ESI-MS) and 1H
      NMR.

PMID- 16620862
TI  - Assessing the trihalomethane formation potential of aquatic fulvic and humic
      acids fractionated using thin-layer chromatography.
AB  - The significance of this research is the application of thin-layer chromatography
      (TLC) to fractionate well-characterized aquatic humic materials coupled with the
      novel evaluation of the trihalomethane formation potential (THMFP) of the
      fractionated materials. Disinfection by-products such as trihalomethanes (THMs)
      form when natural water is treated by chlorination. Nordic Aquatic and Suwannee
      River fulvic and humic acids, obtained from the International Humic Substances
      Society, were prepared at pH 6 and 9 and fractionated on silica gel plates using
      a mobile phase consisting of methanol and ethyl acetate (2:1, v:v). Based on
      retention factor (R(f)) values, three common fractions were identified in all
      substances examined. Additionally, other fractions were noted that were
      characteristic of specific humic substances. Each of the three primary fractions
      derived from Nordic Aquatic fulvic acid at pH 6 demonstrated the potential to
      contribute to formation of THMs. This research provides data to support the
      hypothesis that differences in the chemical structure and composition of natural
      organic matter (NOM) significantly affect the potential to react with chlorine to
      form THMs.

PMID- 16620864
TI  - Solid-phase microextraction of N-nitrosamines.
AB  - A method was developed for the extraction of seven N-nitrosamine compounds from
      water by solid-phase microextraction (SPME). The method developed requires a
      total analysis time of only 1.25 h for both extraction and detection (versus 3-20
      h for other isolation techniques). Three gas chromatography (GC) detection
      systems were tested with the SPME method, nitrogen chemiluminesence detection
      (NCD), nitrogen-phosphorus detection (NPD) and chemical ionization mass
      spectrometry (CI-MS), with method detection limits (MDLs) found in the ng/L
      range. This method was used to analyze wastewater samples and showed excellent
      selectivity of extraction. The detection limits of this method for N
      nitrosodimethylamine (NDMA) range from 30 to 890 ng/L as a function of detector
      type. The excellent selectivity of SPME in addition to the fast analysis time
      would make this method ideal for general surveys, wastewater analysis and
      laboratory studies (e.g. degradation kinetics or formation potential).

PMID- 16620863
TI  - Retention mechanism of L-glutamide-derived noncrystalline stationary phases in
      reversed-phase high-performance liquid chromatography and application for
      separation of nucleic acid constituents.
AB  - Double alkylated L-glutamide-derived noncrystalline stationary phases Sil-DSG and
      Sil-DBG have been prepared by coupling N',N''-dioctadecyl-N-[4-carboxybutanoyl]-L
      glutamide (DSG) and N',N'',-dibutyl-N-[4-carboxybutanoyl]-L-glutamide (DBG) with
      aminopropylated silica (Sil-APS). TEM observations of DSG and DBG showed that
      lipid DSG can aggregate in organic solvents (methanol, chloroform, toluene, etc.)
      and self-assembled nano fibers are observed while such fibrous aggregations are
      not observed for DBG. The resulting chromatographic data have been provided
      information about its selective interaction with guest molecules (PAHs) in RP
      HPLC. We have observed that the carbonyl groups in Sil-DSG exist in ordered state
      by forming a condensing thin layer over silica surface while DBG cannot form such
      an ordered state due to its lower order of short alkyl chain. The ordered
      carbonyl groups present in Sil-DSG promotes multiple carbonyl pi-benzene pi
      interactions with guest PAHs isomers which enhance the selectivity for these
      compounds. The contribution of pi-pi interactions was also supported by the
      substantial effects on the selectivity of benzene and nitrobenzenes. The effect
      of pi-electron containing solvent on the retention behavior of the PAHs was also
      studied. The selectivity for nucleic acid constituents, i.e. nucleosides and its
      bases were also evaluated by Sil-DSG and the selectivity for these compounds on
      Sil-DSG was compared with the selectivity of conventional polymeric ODS phase. It
      has been found that Sil-DSG provided higher selectivity for nucleic acid
      constituents than polymeric ODS and that HPLC packing materials can be
      efficiently employed for routine analysis of these compounds. The effect of
      methanol content on the separation behavior of nucleosides was also studied.

PMID- 16620865
TI  - Liquid chromatography on porous graphitic carbon with atmospheric pressure
      photoionization mass spectrometry and tandem mass spectrometry for the analysis
      of glycosphingolipids.
AB  - The study of several structural variations (the length, the degree of
      unsaturation and hydroxylation of the alkyl chains, the number and nature of
      osidic residues) helped understand the behaviour of neutral glycosphingolipids
      (GSLs) on porous graphitic carbon stationary phase (PGC). Atmospheric pressure
      photoionization mass spectrometry (APPI) and tandem mass spectrometry were used
      to perform the detection and the identification of molecular species in positive
      mode where [M+H](+) and [M-H(2)O+H](+) ions provided structural information on
      the fatty acid and the sphingoid base. The retention of GSLs increased with the
      hydrocarboneous volume of their alkyl chains and with the number of osidic
      residues in agreement with hydrophobic properties and polar retention effect of
      graphite, respectively. The presence of polar groups, such as OH-group or double
      bond within alkyl chains, decreased their retention. The coupling of
      chromatography on PGC with APPI tandem mass spectrometry detection appeared a
      powerful technique to discriminate isobaric molecules. Isobaric solutes differing
      by the position of two double bonds or by the repartition of hydrocarboneous
      skeleton were discriminated according to their chromatographic comportment or
      their mass spectrum, respectively. Among isobaric molecules, only few structures
      differing by the nature of osidic residue were not discriminated (i.e.
      glucosylceramide and galactosylceramide with similar ceramide skeleton were co
      eluted and no difference in mass spectra was observed).

PMID- 16620866
TI  - Color terms and color concepts.
AB  - In their lead articles, both Kowalski and Zimiles (2006) and O'Hanlon and
      Roberson (2006) declare a general relation between color term knowledge and the
      ability to conceptually represent color. Kowalski and Zimiles, in particular,
      argue for a priority for the conceptual representation in color term acquisition.
      The complexities of the interaction are taken up in the current commentary,
      especially with regard to the neuropsychological evidence. Data from aphasic
      patients also argue for a priority for abstract thought, but nevertheless it may
      still be that the use of color terms is the only way in which to form color
      categories even if both linguistic and attentional factors play an important
      role.

PMID- 16620867
TI  - Children's development of analogical reasoning: insights from scene analogy
      problems.
AB  - We explored how relational complexity and featural distraction, as varied in
      scene analogy problems, affect children's analogical reasoning performance.
      Results with 3- and 4-year-olds, 6- and 7-year-olds, 9- to 11-year-olds, and 13-
      and 14-year-olds indicate that when children can identify the critical structural
      relations in a scene analogy problem, development of their ability to reason
      analogically interacts with both relational complexity and featural distraction.
      Error patterns suggest that children are more likely to select a distracting
      object than to make a relational error for problems that present both
      possibilities. This tendency decreases with age, and older children make fewer
      errors overall. The results suggest that changes in analogical reasoning with age
      depend on the interplay among increases in relational knowledge, the capacity to
      integrate multiple relations, and inhibitory control over featural distraction.

PMID- 16620869
TI  - A physical model for galvanotaxis of Paramecium cell.
AB  - We propose a qualitative physical model of galvanotaxis of Paramecium cells using
      a bottom-up approach to link the microscopic ciliary motion and the macroscopic
      behavior of the cells. From the characteristic pattern of ciliary motion called
      the Ludloff phenomenon, the torque that orients the cell toward the cathode is
      derived mathematically. Dynamical equations of motion are derived and their
      stability is discussed. In numerical simulations using our model, cells exhibit
      realistic behavior, such as U-turns, like real cells.

PMID- 16620868
TI  - Direct effects of snowdrop lectin (GNA) on larvae of three aphid predators and
      fate of GNA after ingestion.
AB  - Plants genetically modified to express Galanthus nivalis agglutinin (GNA) have
      been found to confer partial resistance to homopteran pests. Laboratory
      experiments were conducted to investigate direct effects of GNA on larvae of
      three species of aphid predators that differ in their feeding and digestive
      physiology, i.e. Chrysoperla carnea, Adalia bipunctata and Coccinella
      septempunctata. Longevity of all three predator species was directly affected by
      GNA, when they were fed a sucrose solution containing 1% GNA. However, a
      difference in sensitivity towards GNA was observed when comparing the first and
      last larval stage of the three species. In vitro studies revealed that gut
      enzymes from none of the three species were able to break down GNA. In vivo feed
      chase studies demonstrated accumulation of GNA in the larvae. After the larvae
      had been transferred to a diet devoid of GNA, the protein stayed present in the
      body of C. carnea, but decreased over time in both ladybirds. Binding studies
      showed that GNA binds to glycoproteins that can be found in the guts of larvae of
      all three predator species. Immunoassay by Western blotting of haemolymph samples
      only occasionally showed the presence of GNA. Fluorescence microscopy confirmed
      GNA accumulation in the midgut of C. carnea larvae. Implications of these
      findings for non-target risk assessment of GNA-transgenic crops are discussed.

PMID- 16620870
TI  - Travelling waves and EEG patterns during epileptic seizure: analysis with an
      integrate-and-fire neural network.
AB  - Epilepsy is characterized by paradoxical patterns of neural activity. They may
      cause different types of electroencephalogram (EEG), which dynamically change in
      shape and frequency content during the temporal evolution of seizure. It is
      generally assumed that these epileptic patterns may originate in a network of
      strongly interconnected neurons, when excitation dominates over inhibition. The
      aim of this work is to use a neural network composed of 50 x 50 integrate-and
      fire neurons to analyse which parameter alterations, at the level of synapse
      topology, may induce network instability and epileptic-like discharges, and to
      study the corresponding spatio-temporal characteristics of electrical activity in
      the network. We assume that a small group of central neurons is stimulated by a
      depolarizing current (epileptic focus) and that neurons are connected via a
      Mexican-hat topology of synapses. A signal representative of cortical EEG (ECoG)
      is simulated by summing the membrane potential changes of all neurons. A
      sensitivity analysis on the parameters describing the synapse topology shows that
      an increase in the strength and in spatial extension of excitatory vs. inhibitory
      synapses may cause the occurrence of travelling waves, which propagate along the
      network. These propagating waves may cause EEG patterns with different shape and
      frequency, depending on the particular parameter set used during the simulations.
      The resulting model EEG signals include irregular rhythms with large amplitude
      and a wide frequency content, low-amplitude high-frequency rapid discharges,
      isolated or repeated bursts, and low-frequency quasi-sinusoidal patterns. A slow
      progressive temporal variation in a single parameter may cause the transition
      from one pattern to another, thus generating a highly non-stationary signal which
      resembles that observed during ECoG measurements. These results may help to
      elucidate the mechanisms at the basis of some epileptic discharges, and to relate
      rapid changes in EEG patterns with the underlying alterations at the network
      level.

PMID- 16620871
TI  - A stochastic model in tumor growth.
AB  - A stochastic model of solid tumor growth based on deterministic Gompertz law is
      presented. Tumor cells evolution is described by a one-dimensional diffusion
      process limited by two absorbing boundaries representing healing threshold and
      patient death (carrying capacity), respectively. Via a numerical approach the
      first exit time problem is analysed for the process inside the region restricted
      by the boundaries. The proposed model is also implemented to simulate the effects
      of a time-dependent therapy. Finally, some numerical results are obtained for the
      specific case of a parathyroid tumor.

PMID- 16620872
TI  - Investigation of mangrove macroalgae as bioindicators of estuarine contamination.
AB  - This study examined the potential use of macroalgae epiphytic on mangrove aerial
      roots as indicators of estuarine contamination. The distribution and abundance of
      macroalgae was investigated in four estuaries in the vicinity of Sydney,
      Australia, and compared to water and sediment metal concentrations, nutrient
      concentrations and physicochemical parameters over four seasonal surveys.
      Macroalgal diversity and distribution appeared to be highly influenced by the
      ambient contaminant concentrations, while biomass appeared to be linked with
      nutrient concentrations. The distribution of the Rhodophyta species, Catenella
      nipae Zanardini significantly decreased as metal concentrations increased among
      the estuaries during all seasonal surveys. This species showed strong potential
      for use as a bioindicator of estuarine contamination.

PMID- 16620873
TI  - Microbiological 'bottle effects' are not to be ignored (a comment on Mimura et
      al., 2005).

PMID- 16620874
TI  - Contaminant assessment of surface sediments from Tanapag Lagoon, Saipan,
      Commonwealth of the Northern Mariana Islands.

PMID- 16620875
TI  - The effect of contact heterogeneity and multiple routes of transmission on final
      epidemic size.
AB  - Heterogeneity in the number of potentially infectious contacts amongst members of
      a population increases the basic reproduction ratio (R(0)) and markedly alters
      disease dynamics compared to traditional mean-field models. Most models
      describing transmission on contact networks only account for one specific route
      of transmission. However, for many infectious diseases multiple routes of
      transmission exist. The model presented here captures transmission through a well
      defined network of contacts, complemented by mean-field type transmission amongst
      the nodes of the network that accounts for alternative routes of transmission.
      The impact of these combined transmission mechanisms on the final epidemic size
      is investigated analytically. The analytic predictions for the purely mean-field
      case and the transmission through the network-only case are confirmed by
      individual-based network simulations. There is a critical transmission potential
      above which an increased contribution of the mean-field type transmission
      increases the final epidemic size while an increased contribution of the
      transmission through the network decreases it. Below the critical transmission
      potential the opposite effect is observed.

PMID- 16620876
TI  - Modeling the impact of store-operated Ca2+ entry on intracellular Ca2+
      oscillations.
AB  - Calcium (Ca2+) oscillations play fundamental roles in various cell signaling
      processes and have been the subject of numerous modeling studies. Here we have
      implemented a general mathematical model to simulate the impact of store-operated
      Ca2+ entry on intracellular Ca2+ oscillations. In addition, we have compared two
      different models of the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) and
      their influences on intracellular Ca2+ oscillations. Store-operated Ca2+ entry
      following Ca2+ depletion of endoplasmic reticulum (ER) is an important component
      of Ca2+ signaling. We have developed a phenomenological model of store-operated
      Ca2+ entry via store-operated Ca2+ (SOC) channels, which are activated upon ER
      Ca2+ depletion. The depletion evokes a bi-phasic Ca2+ signal, which is also
      produced in our mathematical model. The IP3R is an important regulator of
      intracellular Ca2+ signals. This IP3 sensitive Ca2+ channel is also regulated by
      Ca2+. We apply two IP3R models, the Mak-McBride-Foskett model and the De Young
      and Keizer model, with significantly different channel characteristics. Our
      results show that the two separate IP3R models evoke intracellular Ca2+
      oscillations with different frequencies and amplitudes. Store-operated Ca2+ entry
      affects the oscillatory behavior of these intracellular Ca2+ oscillations. The
      IP3 threshold is altered when store-operated Ca2+ entry is excluded from the
      model. Frequencies and amplitudes of intracellular Ca2+ oscillations are also
      altered without store-operated Ca2+ entry. Under certain conditions, when
      intracellular Ca2+ oscillations are absent, excluding store-operated Ca2+ entry
      induces an oscillatory response. These findings increase knowledge concerning
      store-operated Ca2+ entry and its impact on intracellular Ca2+ oscillations.

PMID- 16620877
TI  - How diseases affect symbiotic communities.
AB  - Examples of species living in symbiotic communities are well known among
      biologists. In this study we extend our previous analysis of predator-prey or
      competing models subject to a disease spreading among one of the species to
      populations mutually benefiting from interactions. We assume that one of the
      species is subject to a disease which cannot cross the species barrier and
      investigate the behavior of such a community. Our findings indicate that there
      are parameter ranges for which an interesting phenomenon occurs. Namely, the
      equilibrium shifts to a higher value. That is, the disease seems to have a
      positive effect on the environment as also field experiments show.

PMID- 16620878
TI  - Methylation and repeats in silent and nonsense mutations of p53.
AB  - All exonic CG sequences in p53 are methylated; this epigenetic modification is
      correlated with frequent G:C-->A:T transitions in p53. Recent reports reveal the
      presence in p53 of non-CG methylation in CC and CCC sequences, complementary to
      sites of selective guanosine adduct formation (GG and GGG), and the association
      of genetic instability with methylation at repetitive sequences. We presently
      investigated the distribution of methylation sites and repetitive elements in
      silent and nonsense p53 mutations (2051) among the IARC's TP53 somatic mutation
      database for exons 5-8. Silent mutations are nonrandom, but mostly involve G:C-
      >A:T transitions (62%); in particular C-->T mutations (39% of all silent
      mutations) are mostly correlated with CC and CCC sequences, while G-->A mutations
      with GG sequences. Sequence analysis of all non-G:C-->A:T silent mutations
      reveals the frequent formation of new methylation sites (CG), new CCC and GGG
      sequences in the resulting sequence, refinement of symmetry elements at
      interrupted microsatellite-like sequences and formation of small repeats (55.3%).
      The G:C-->A:T silent mutations characterize cancers associated with cigarette
      smoking (e.g. bladder or lung and bronchus cancer versus colorectal cancer); on
      the contrary, non-G:C-->A:T silent mutations have similar frequencies in most
      cancers. Nonsense mutations in exons 5-8, all resulting in mutants lacking amino
      acids 307-393, which are crucial for p53 activity, were also analyzed. The
      frequency of nonsense mutations is higher at methylated sites or repeats 1-2
      nucleotides removed from methylation sites. Frameshift mutations are also more
      frequent at repeated sequences. The frequent G:C-->A:T silent mutations could
      indicate that CC and CCC sequences of exons 5-8 are occasionally targets of non
      CpG methylation of cytosine. This process of de novo methylation in the presence
      of microsatellite-like sequences and small repeats might influence the genetic
      stability of a variety of genes.

PMID- 16620879
TI  - Chromatin condensation and differential sensitivity of mammalian and insect cells
      to DNA strand breaks induced by bleomycin.
AB  - Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed
      the role of chromatin compactness in the differential response of mosquito (ATC
      15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells
      unexposed and exposed to sodium butyrate (NaB), which induces chromatin
      decondensation. By nucleoid sedimentation assay and digestions of nuclei with
      DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more
      chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15
      cells treated with NaB showed more BLM-induced DNA strand breaks than NaB
      untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was
      similar for NaB-untreated mammalian and insect cells, but with mosquito cells
      showing less DNA strand breaks, both at physiological temperatures and at 4
      degrees C. However, when DNA repair was inhibited by low temperatures and
      chromatin was decondensed by NaB treatments, differences in BLM-induced DNA
      damage between these cells lines were no longer observed. In both cell lines, NaB
      did not affect BLM action on cell growth and viability. On the other hand, the
      low sensitivity of ATC-15 cells to BLM was reflected in their better growth
      efficiency. These cells exhibited a satisfactory growth at BLM doses that
      produced a permanent arrest of growth in CHO cells. The data suggest that
      mosquito cells might have linker DNAs shorter than those of mammalian cells,
      which would result in the observed both greater chromatin condensation and
      greater resistance to DNA damage induced by BLM as compared to CHO cells.

PMID- 16620880
TI  - Endogenous opioids mediate the hypoalgesia induced by selective inhibitors of
      cyclo-oxygenase 2 in rat paws treated with carrageenan.
AB  - Mechanical hyperalgesia induced in rat paws by carrageenan (250microg) was
      modified by pre-treatment with three selective inhibitors of cyclo-oxygenase-2
      (COX-2); celecoxib, rofecoxib and SC236. These inhibitors raised the nociceptive
      threshold above the normal, non-inflamed, level, inducing a state of hypoalgesia.
      Such hypoalgesia was observed in different strains of rat (Holtzman, Wistar and
      Sprague-Dawley) and after different modes of administration of the COX-2
      inhibitor (locally, in the paw, or systemically). A selective inhibitor of COX-1
      (SC 560; 1-10mg kg(-1)) decreased hyperalgesia but did not induce hypoalgesia.
      Pre-treatment with naltrexone (3mg kg(-1)), an opioid receptor antagonist, did
      not affect carrageenan-induced hyperalgesia but abolished the hypoalgesic effects
      of COX-2 inhibitors, without diminishing the anti-hyperalgesic effect of
      indomethacin. In rats made tolerant to the anti-nociceptive effects of morphine,
      all anti-nociceptive effects of SC236 were abolished but the anti-hyperalgesic
      effects of indomethacin or SC 560 were unaffected. We conclude that, in our model
      of inflammatory hyperalgesia, the anti-nociceptive effect of selective COX-2
      inhibitors involved the participation of endogenous opioids.

PMID- 16620881
TI  - Airjet and FG-7142-induced Fos expression differs in rats selectively bred for
      high and low anxiety-related behavior.
AB  - We reported recently that two rat lines bred for either high (HAB) or low (LAB)
      anxiety-related behavior display differential Fos expression in restricted parts
      of the fear/anxiety circuitry when exposed to mild anxiety evoked in exploratory
      anxiety tests. Since different forms of anxiety are thought to activate different
      parts of the anxiety circuitry, we investigated now whether (1) an aversive
      stimulus which elicits escape behavior (airjet) and (2) the
      anxiogenic/panicogenic drug FG-7142 would reveal further differences in Fos
      expression as a marker of neuronal activation between HAB and LAB rats. Both
      airjet exposure and FG-7142 induced Fos expression in both lines in various
      anxiety-related brain areas. HAB rats, which displayed exaggerated escape
      responses during airjet exposure, exhibited increased Fos expression in brain
      areas including the hypothalamus, periaqueductal gray and locus coeruleus, as
      well as blunted Fos activation in the cingulate cortex in response to airjet
      and/or FG-7142. The results corroborate previous findings showing that trait
      anxiety affects neuronal excitability in hypothalamic and medial prefrontal
      areas. Furthermore, by using airjet as well as FG-7142, we now reveal that
      enhanced trait anxiety is also associated with neuronal hyperexcitability in the
      locus coeruleus and the periaqueductal gray, suggesting that investigation of an
      array of different anxiogenic stimuli is important for the detection of altered
      neuronal processing in trait anxiety.

PMID- 16620882
TI  - Seeking a mechanism of action for the novel anticonvulsant lacosamide.
AB  - Lacosamide (LCM) is anticonvulsant in animal models and is in phase 3 assessment
      for epilepsy and neuropathic pain. Here we seek to identify cellular actions for
      the new drug and effects on recognised target sites for anticonvulsant drugs.
      Radioligand binding and electrophysiology were used to study the effects of LCM
      at well-established mammalian targets for clinical anticonvulsants. 10 microM LCM
      did not bind with high affinity to a plethora of rodent, guinea pig or human
      receptor sites including: AMPA; Kainate; NMDA (glycine/PCP/MK801); GABA(A)
      (muscimol/benzodiazepine); GABA(B); adenosine A1,2,3; alpha1, alpha2; beta1,
      beta2; M1,2,3,4,5; H1,2,3; CB1,2; D1,2,3,4,5; 5HT1A,1B,2A,2C,3,5A,6,7 and KATP.
      Weak displacement (25%) was evident at batrachotoxin site 2 on voltage gated Na+
      channels. LCM did not inhibit neurotransmitter transport mechanisms for
      norepinephrine, dopamine, 5-HT or GABA, nor did it inhibit GABA transaminase. LCM
      at 100 microM produced a significant reduction in the incidence of excitatory
      postsynaptic currents (EPSC's) and inhibitory postsynaptic currents (IPSC's) in
      cultured cortical cells and blocked spontaneous action potentials (EC50 61
      microM). LCM did not alter resting membrane potential or passive membrane
      properties following application of voltage ramps between -70 to +20 mV. The
      voltage-gated sodium channel (VGSC) blocker phenytoin potently blocked sustained
      repetitive firing (SRF) but, in contrast, 100 microM LCM failed to block SRF. No
      effect was observed on voltage-clamped Ca2+ channels (T-, L-, N- or P-type).
      Delayed-rectifier or A-type potassium currents were not modulated by LCM (100
      microM). LCM did not mimic the effects of diazepam as an allosteric modulator of
      GABA(A) receptor currents, nor did it significantly modulate evoked excitatory
      neurotransmission mediated by NMDA or AMPA receptors (n > or = 5). Evidently LCM
      perturbs excitability in primary cortical cultures but does not appear to do so
      via a high-affinity interaction with an acknowledged recognition site on a target
      for existing antiepileptic drugs.

PMID- 16620883
TI  - Opposing effects of AMPA and 5-HT1A receptor blockade on passive avoidance and
      object recognition performance: correlation with AMPA receptor subunit expression
      in rat hippocampus.
AB  - It has been suggested that antagonists at serotonin 5-HT1A receptors may exert a
      procognitive effect by facilitating glutamatergic neurotransmission. Here we
      further explored this issue by looking for the ability of a 5-HT1A antagonist to
      prevent the learning deficit induced by AMPA receptor blockade in two behavioural
      procedures in rats, and for concomitant molecular changes presumably involved in
      memory formation in the hippocampus. Pretraining administration of the
      competitive AMPA receptor antagonist, NBQX, produced a dose-related retention
      impairment in a passive avoidance task 24h later, and also impaired retention in
      a novel object recognition test when an intertrial interval of 3h was selected.
      Pretreatment with the selective 5-HT1A receptor antagonist, WAY-100635, prevented
      the learning deficit induced by NBQX in the two behavioural procedures. In
      biochemical studies performed on rat hippocampus after the retention tests, we
      found that learning increased the membrane levels of AMPA receptor GluR1 and
      GluR2/3 subunits, as well as the phosphorylated forms of GluR1, effects that were
      abolished by NBQX administration before the training session. Pretreatment with
      WAY-100635 counteracted the NBQX effects and restored the initial learning
      specific increase in Ca2+/calmodulin-dependent protein kinase II (CaMKII)
      function and the later increase in GluR2/3 and phosphorylated GluR1 surface
      expression. Moreover, administration of WAY-100635 before object recognition
      training improved recognition memory 24h later and potentiated the learning
      associated increase in AMPA receptor subunits. The results support the proposed
      utility of 5-HT1A antagonists in the treatment of cognitive disorders.

PMID- 16620884
TI  - Utilizing the ventriloquism-effect to investigate audio-visual binding.
AB  - Audio-visual binding - as subset of crossmodal integration - describes the
      combination of information across both these senses to the subjective unified
      perception of a bound object. We investigated audio-visual binding by using the
      ventriloquism-effect (localization of a sound is biased towards and by a
      simultaneous visual stimulus) to act as an indicator for perceived binding.
      Simple visual and auditory stimuli were presented synchronously or
      asynchronously. fMRI was recorded during task performance (n = 19 subjects) in
      order to reveal activation in areas discussed to be involved in multisensory
      processing in the literature. Contrasting trials with reported ventriloquism
      effect versus the no-binding condition revealed activation in the insula,
      superior temporal sulcus and parieto-occipital sulcus. Implementing the
      ventriloquism-effect allows us to relate these activations to consciousness
      related processes, which probably are different from stimulus-driven multisensory
      integration in subcortical areas.

PMID- 16620885
TI  - Unimpaired negative but enhanced positive priming in Parkinson's disease:
      evidence from an identity and a location priming task.
AB  - Mechanisms of selective attention are frequently reported to be impaired in
      Parkinson's disease (PD). Fundamental to selective attention is attending to
      relevant information and, concurrently, ignoring irrelevant information. Both
      processes can be assessed by positive priming (PP) and negative priming (NP)
      tasks, respectively. Unlike previous studies, in the present experiment, two
      separate identity- and location-based priming tasks were applied to 48 PD
      patients and 48 sex- and age-matched healthy controls. Results indicated that
      identity and location PP were reliably enhanced in PD patients compared to
      controls. Both groups showed significant location NP of almost identical
      magnitude but no identity NP. However, there was evidence for a positive
      functional relationship between severity of bradykinesia and identity NP.
      Furthermore, with increasing depression scores, location NP was enhanced in PD
      patients but not in controls. These findings suggest that disturbed selective
      attention associated with PD is due to changed mechanisms mediating attention to
      relevant information rather than due to mechanisms involved in inhibition of
      irrelevant information.

PMID- 16620886
TI  - Induced gamma-band oscillations correlate with awareness in hemianopic patient
      GY.
AB  - In normal vision gamma oscillations are involved in object perception, are
      modulated by attention, and have been linked to awareness by way of their
      putative role in perceptual integration, arguably as a mechanism for
      synchronizing activity in separate neural assemblies. We tested the hypothesis
      that the presence of gamma oscillations (approximately 30-80 Hz) signal the entry
      of a neural representation into awareness (as indexed by direct report), while
      attempting to control for other measures of neural information processing such as
      discrimination accuracy and reaction time. Hemianopic patient GY sometimes
      reports an awareness "that something happened" in his blind visual hemifield, in
      response to stimuli of sufficiently high contrast, although he may deny "seeing"
      anything. At lower contrast levels GY denies any awareness, but may continue to
      exhibit greater-than-chance accuracy (blindsight). Using a near-threshold level
      of contrast offers a unique way to test hypotheses concerning correlates of
      perceptual awareness, since GY's accuracy on certain tasks is independent of
      awareness. We tested GY on an orientation-discrimination task using stationary
      stimuli at a fixed near-threshold level of contrast, to which GY sometimes
      responded "aware" and sometimes "unaware". We recorded brain activity using
      magnetoencephalography (MEG) in order to determine the relationship between local
      induced gamma-band oscillations and awareness. GY's accuracy was significantly
      greater than expected by chance and no different whether or not he reported
      awareness of the stimulus. Oscillatory activity in the gamma band (44-66 Hz) over
      the left occipito-parietal region correlated significantly with awareness (but
      not accuracy), whereas activity in the alpha band (8-12 Hz) did not.

PMID- 16620887
TI  - Preserved implicit form perception and orientation adaptation in visual form
      agnosia.
AB  - Visual form agnosia is mainly characterized by profound deficits in visual form
      and shape discrimination. Previous studies have shown that patients retain the
      capacity for coordinated motor behaviors, color naming and implicit letter
      perception. However, it is unknown to what extent other visual functions, such as
      implicit form and orientation perception, are preserved. To address these
      questions, we investigated a single visual form agnosic patient, X.F., in two
      distinct experiments. X.F.'s visual lesions were mainly localized in the
      bilateral occipitotemporal cortex, with the dorsal visual stream and early visual
      cortex largely spared. In Experiment 1, X.F. named the color of different forms
      across 12 blocks of trials. After the first six blocks, the combinations of a
      form with its color were changed and the new combination was presented for the
      remaining six blocks. X.F.'s reaction time increased during the switch block and
      was significantly greater than the overall RT changes between adjacent, non
      switch blocks. This indicates that X.F. retained the ability to perceive changes
      in form despite her inability to discriminate the forms. In Experiment 2, X.F.
      showed selective orientation adaptation effects to different spatial frequencies;
      that is, her contrast threshold was significantly higher when the adapting and
      test orientations were the same than when they were orthogonal, although her
      orientation discrimination performance was severely impaired. These data provide
      evidence of a functional dissociation between explicit and implicit visual
      abilities, and suggest that the residual early visual cortex mediates form and
      orientation processing in the absence of awareness.

PMID- 16620888
TI  - You can play 20 questions with nature and win: categorical versus coordinate
      spatial relations as a case study.
AB  - Alan Newell famously asserted that "You can't play 20 questions with nature and
      win" (Newell, A. (1973). You can't play 20 questions with nature and win. In W.G.
      Chase (Ed.), Visual information processing. New York: Academic Press.), and
      specifically focused on the futility of studying binary distinctions. However,
      the distinction between categorical and coordinate spatial relations
      representations has turned out to be fruitful. In this brief article, the
      categorical/coordinate distinction is treated as a case study, as a way to
      address a more general point, namely how to play 20 questions with nature and
      win. The key to studying binary distinctions may lie in the ways this one differs
      from previous ones. First, from the outset this distinction was cast within the
      context of a theory of a more general processing system; second, it was
      formulated from the perspective of multiple levels of analysis within a
      processing system, and thereby bridges characteristics of information processing
      with characteristics of the brain.

PMID- 16620889
TI  - Changes over time in cognitive and structural profiles of head injury survivors.
AB  - Survivors of traumatic head injury often suffer chronic cognitive deficits.
      Considerable evidence implicates the cholinergic system in these deficits.
      Recently, we reported cognitive and structural abnormalities in a cohort of head
      injured survivors consistent with this hypothesis [see Salmond, C. H., Chatfield,
      D. A., Menon, D. K., Pickard, J. D., & Sahakian, B. J. (2005). Cognitive Sequelae
      of Head Injury: Involvement of Basal Forebrain and associated structures. Brain,
      128(1), 189-200]. The stability of the cognitive and structural MRI profiles was
      investigated in a longitudinal study. Twenty-one survivors of moderate-severe
      head injury completed two comprehensive neuropsychological assessments and two
      structural MRI scans at least six months apart. A cohort of controls also
      completed these investigations. The results revealed that the cognitive and
      structural profiles are relatively stable from six months post-injury forward up
      to 3 years post-injury. Deficits in memory, attention and reaction time were
      found, with relative preservation of working memory, consistent with
      abnormalities in the cholinergic system. These findings suggest that cholinergic
      enhancers may be an effective treatment for cognitive deficits post-head injury
      in survivors up to three years post-injury.

PMID- 16620890
TI  - Evidence for a dysfunction of left posterior reading areas in German dyslexic
      readers.
AB  - The brain activity during a sentence reading task and a visual control task was
      examined with fMRI in 13 German dyslexic readers and 15 age-matched fluent
      readers (age: 14-16 years). These participants came from a longitudinal study and
      the dyslexic readers exhibited a persistent reading fluency deficit from early
      on. For the first time with German dyslexic readers, and in correspondence with
      the majority of functional imaging studies, we found reduced dyslexic activation
      in the left occipitotemporal cortex and in a small region of the left
      supramarginal gyrus. Enhanced activation was found in left inferior frontal and
      subcortical regions.

PMID- 16620891
TI  - Vitamin E deficiency enhances pathology in acute Trypanosoma cruzi-infected rats.
AB  - Micronutrient malnutrition is usually highly prevalent in areas endemic for
      Chagas disease. Nevertheless, the contribution of micronutrient deficiency to the
      immunopathology of this infection is often overlooked. In the present work, we
      assessed the effects of vitamin E deficiency on acute Trypanosoma cruzi (Y
      strain) infection of Holtzman rats. At 20 days post infection, vitamin E
      deficiency induced changes in leukocyte levels and exacerbated the myocarditis
      and sympathetic denervation of ventricular hearts. Vitamin E-deficient infected
      rats displayed significant leukopenia, evidenced by the decline in the numbers of
      CD45RA(+)CD3(-) B-cells and CD3(+)CD4(+) T-lymphocytes in the peripheral blood
      compared with infected control rats. In contrast, vitamin E deficiency induced
      monocytosis as well as an increased differentiation rate of monocytes to
      macrophages, as revealed by immunohistochemical analysis.

PMID- 16620892
TI  - Development of molecular approaches for the identification of transmission sites
      of schistosomiasis.
AB  - Primers targeting the gene encoding the small subunit rRNA were designed to
      amplify DNA from Schistosoma mansoni with high specificity. Three PCR systems
      were developed: conventional PCR, two-step nested PCR (NPCR) and single-tube
      nested PCR (STNPCR). The limits of detection of parasite DNA for the conventional
      PCR, NPCR and STNPCR were 10 pg, 0.1 fg and 1 fg, respectively. The assays were
      highly specific for S. mansoni and did not recognise DNA from closely related non
      schistosome trematodes. Using pools of Biomphalaria molluscs, PCR, NPCR and
      STNPCR were positive in 6/16 (37.5%), 15/16 (93.8%) and 13/16 (81.3%) of the
      tested samples, respectively, whereas the observation of cercariae shedding after
      exposure to light was able to detect S. mansoni infection in 6/16 (37.5%) of the
      pools. Thus, the molecular detection systems had a higher level of sensitivity
      than standard screening of intermediate hosts by cercarial shedding when DNA was
      purified from pools of snails collected from endemic areas. These PCR protocols
      have potential to be used as tools for monitoring of schistosome transmission.

PMID- 16620893
TI  - Studies on neurosteroids XVIII LC-MS analysis of changes in rat brain and serum
      testosterone levels induced by immobilization stress and ethanol administration.
AB  - The liquid chromatography-mass spectrometry (LC-MS) methods were developed and
      validated for the determination of testosterone (T) in the brain and serum of
      rats and of 5alpha-androstane-3alpha,17beta-diol (ADIOL), a metabolite of T, in
      the brain of rats. After derivatization of T with 2-hydrazino-1-methylpyridine
      and of ADIOL with p-nitrobenzoyl chloride, the detection sensitivities of T and
      ADIOL using LC-MS were increased 70- and 400-times superior to those of intact T
      and intact ADIOL, respectively. Those LC-MS methods are specific and reliable for
      the analysis of trace amounts of T and ADIOL in small amounts of samples. The
      animal studies using the developed methods showed that the brain and serum levels
      of T and the brain levels of ADIOL were not changed by stress or ethanol
      administration but the concentration ratio of the brain T to serum T in the
      stressed rats was higher than that in untreated rats. The low levels of
      endogenous AIDOL in brain of stressed and unrestrained rats found in this study
      demonstrated that the contribution to anesthetic and anxiolytic effects of ADIOL
      via gamma-aminobutyric acid type A receptors may be negligible.

PMID- 16620894
TI  - Short synthesis of 16beta-hydroxy-5alpha-cholestane-3,6-dione a novel cytotoxic
      marine oxysterol.
AB  - The first and short synthesis of 16beta-hydroxy-5alpha-cholestane-3,6-dione 1 a
      metabolite from marine algae, has been achieved in six steps from readily
      available diosgenin 5. Selective deoxygenation of primary alcohol of triol 6 has
      been accomplished in one step using Et(3)SiH and catalytic amount of
      B(C(6)F(5))(3) to produce compound 9 in high yield. Oxidation of 11 with PCC,
      allowed the introduction of 3,6-ene-dione functionality, and further catalytic
      hydrogenation and deprotection furnished the 3,6-diketo steroid 1.

PMID- 16620895
TI  - Synthesis and stereochemical investigations of novel nitrogen-containing 13alpha
      estrone derivatives.
AB  - Novel tetrahydroquinoline 11 and N-aryl d-homo derivatives 12 in the 13alpha
      estrone series were synthesized effectively, starting from the secoaldehyde 8 and
      mono- or disubstituted anilines 9. The chemoselectivity of the cyclization
      reactions depended upon the nature of the substituents in the anilines. All
      transformations proceeded in a highly stereoselective manner, yielding only one
      diastereomer. Condensed 11 and d-homo derivatives 12 both have the usual ring C
      chair conformation in the solid state.

PMID- 16620897
TI  - A theoretical model of the catalytic mechanism of the Delta5-3-ketosteroid
      isomerase reaction.
AB  - The present paper describes a theoretical approach to the catalytic reaction
      mechanism involved in the conversion of 5-androstene-3,17-dione to 4-androstene
      3,17-dione. The model incorporates the side chains of the residues tyrosine
      (Tyr(14)), aspartate (Asp(38)) and aspartic acid (Asp(99)) of the enzyme Delta(5)
      3-ketosteroid isomerase (KSI; EC 5.3.3.1). The reaction involves two steps:
      first, Asp(38) acts as a base, abstracting the 4beta-H atom (proton) from C-4 of
      the steroid to form a dienolate as the intermediate; next, the intermediate is
      reketonized by proton transfer to the 6beta-position. Each step goes through its
      own transition state. Functional groups of the Tyr(14) and Asp(99) side chains
      act as hydrogen bond donors to the O1 atom of the steroid, providing stability
      along the reaction coordinate. Calculations were assessed at high level Hartree
      Fock theory, using the 6-31G(*) basis set and the most important physicochemical
      properties involved in each step of the reaction, such as total energy, hardness,
      and dipole moment. Likewise, to explain the mechanism of reaction, highest
      occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO),
      atomic orbital contributions to frontier orbitals formation, encoded
      electrostatic potentials, and atomic charges were used. Energy minima and
      transition state geometries were confirmed by vibrational frequency analysis. The
      mechanism described herein accounts for all of the properties, as well as the
      flow of atomic charges, explaining both catalytic mechanism and proficiency of
      KSI.

PMID- 16620896
TI  - Bioactive steroids from Oryza sativa L.
AB  - Rice is one of the most interesting crops in the world from both the social and
      the economic point of views. The monoculture practices along with the heavy use
      of herbicides are characteristic of modern agriculture and are inducing the
      appearance of tolerant and/or herbicide resistant weed biotypes. This is the case
      the world's main weed of rice barnyardgrass (Echinochloa crus-galli). Alternative
      strategies for weed suppression consist of the use of chemicals from rice due to
      necessity of obtaining new herbicides with new modes of action that could prevent
      resistance phenomena. In order to carry out a study that guides to the isolation
      of the most active compounds from rice, different extracts were achieved, and
      their activities evaluated. So, all the plant material was divided into three
      parts: fresh plant, dried plant, and fresh plant from Pluviotron. The aerial part
      was separated from roots in all cases and extracted in water, in organic solvents
      as well as with the Pluviotron device. The activity of the 12 extracts obtained
      was evaluated using a generalist bioassay, wheat etiolated coleoptiles bioassay,
      and a phytotoxic bioassay on barnyardgrass as target species. The bioactive
      extracts were fractionated and 15 compounds were isolated and identified by
      spectroscopic methods. Eight of these compounds were isolated for the first time
      in Oryza sativa. The most phytotoxic compounds on E. crus-galli were ergosterol
      peroxide and 7-oxo-stigmasterol. In the case of ergosterol peroxide the activity
      was higher than the commercial herbicide Logran. This is the first report of
      potential allelopathic activity of steroids on weeds based on their
      phytotoxicity.

PMID- 16620898
TI  - The aberrant spermatogenesis of the Haplothrips simplex (Buffa) (Thysanoptera):
      ultrastructural study.
AB  - The aberrant spermatogenesis of the haploid insect Haplothrips simplex
      (Thysanoptera) is described. The process, which occurs in the pupal instars, is
      characterized by two mitotic divisions, the second of which gives rise to two
      different-sized spermatids: the larger spermatids have a nucleus with diffuse
      chromatin and proceed into spermiogenesis, while the small spermatids have
      pycnotic nuclei and degenerate. Both types of spermatids contain two centrioles
      parallely rather than orthogonally oriented. The occurrence of two centrioles
      supports a close relationship between Thysanoptera and Phthyraptera. Before the
      beginning of spermiogenesis, however, the functional spermatids show the unusual
      presence of a third parallel centriole which is formed by the duplication of one
      of the two pre-existing centrioles.

PMID- 16620899
TI  - Comment on "a critical comparison of systematic calibration protocols for
      activated sludge models," by Gurkan Sin, Stijn W.H. Van Hulle, Dirk J.W. De Pauw,
      Ann van Griensven, Peter A. Vanrolleghem, published in Water Res. (39) (2005)
      2460-2474.

PMID- 16620900
TI  - Biological degradation of pharmaceuticals in municipal wastewater treatment:
      proposing a classification scheme.
AB  - A simple classification scheme is suggested to characterize the biological
      degradation of micropollutants such as pharmaceuticals, musk fragrances and
      estrogens during wastewater treatment. The scheme should be a basis for the
      discussion about potential removal efficiencies. Hence, the biological
      degradation of 25 pharmaceuticals, hormones and fragrances was studied in batch
      experiments at typical concentration levels using activated sewage sludge
      originating from nutrient-eliminating municipal wastewater treatment plants.
      Since pseudo first-order degradation kinetics was observed for all compounds down
      to ng L(-1) levels, the removal rates can be predicted for various reactor
      configurations. Therefore dilution of wastewater (e.g. by extraneous water) is
      expected to reduce the degree of biological removal. Wastewater segregation and
      treatment at the source are therefore to be favoured for elimination of
      persistent micropollutants over centralized end-of-pipe treatment. For reactor
      configurations typical for nutrient removal in municipal wastewater, the derived
      formula for predicting removal allows the identification of three groups of
      micropollutants according to their degradation constant k(biol): compounds with
      k(biol)<0.1 L g(SS)(-1)d(-1) are not removed to a significant extent (<20%),
      compounds with k(biol)>10 L g(SS)(-1)d(-1) transformed by >90% and in-between
      moderate removal is expected. Based on the degradation of a heterogeneous group
      of 35 compounds (including literature data), state of the art biological
      treatment schemes for municipal wastewater are not efficient in degrading
      pharmaceuticals: only 4 out of 35 compounds are degraded by more than 90% while
      17 compounds are removed by less than 50%.

PMID- 16620901
TI  - Effects of initial molecular weight on removal rate of dextran in biofilms.
AB  - Degradation kinetics of different size dextrans in a biofilm reactor were
      evaluated. Degradation rates of dextran standards, measured as time series of
      oxygen utilisation rates, decreased with increasing initial molecular weight.
      Removal of bulk phase total organic carbon with time was highly correlated
      (R2>0.99) and could be modelled with variable half-order degradation rate
      expressions. A power correlation between initial molecular weight and the
      variable half-order degradation rate coefficient was found for polymers in the
      range 6-500 kDa. Degradation of dextran in the colloid size range (MW>1 Mda) did
      not follow the same kinetics. Reductions in the observed removal rate with
      polymer size can be explained by the effect of reduced diffusivities of the
      substrate, without assuming reaction rate effects.

PMID- 16620902
TI  - The discriminatory power of two biomonitors of trace metal bioavailabilities in
      freshwater streams.
AB  - The relative discriminatory powers of two trace metal biomonitors in European
      streams (the amphipod crustacean Gammarus fossarum and mayfly larvae of the genus
      Baetis-B. rhodani and B. vernus) are compared by discriminant function analysis
      using data from streams draining a zinc and lead mining area of Upper Silesia,
      Poland. The mayfly larvae (whether or not distinguished into the two separate
      species) had the better discriminatory power to distinguish between sites on the
      basis of local bioavailabilities of cadmium, copper, iron, lead and zinc. The
      bioavailabilities of the two metals lead and cadmium were the major local
      contributing factors to the stronger discrimination shown by the Baetis larvae.

PMID- 16620903
TI  - Comment on "biological removal of polychlorinated dibenzo-p-dioxins from
      incinerator fly ash by Sphingomonas wittichii RW1" by I.-H. Nam, Y.-M. Kim, B.-H.
      Kim, K. Murugesan, and Y.-S. Chang.

PMID- 16620904
TI  - Sewage sludge stabilisation with calcium hydroxide: effect on physicochemical
      properties and molecular composition.
AB  - Raw primary sewage sludge (Wastewater Treatment Plant of Krotoszyn, SW Poland)
      and its mixtures with 3%d, 6%d, 9%d, 12%d and 24%d of calcium hydroxide were
      stabilised for 1 and 35 days. Changes of the sludge physicochemical properties
      and molecular composition, caused by alkaline agent in course of stabilisation
      process, are recognised. A basic physicochemical data on the sludge cake and
      filtrate after 1 and 35 days of stabilisation process are given. Soxhlet extracts
      from the sludge cakes stabilised for 35 days as well pyrolysis and pyrolysis in
      situ methylation (using tetramethylammonium hydroxide-TMAH) products of
      respective pre-extracted cake residues were analysed by gas chromatography-mass
      spectrometry (GC-MS). Increase of calcium hydroxide concentration in the sludge
      mixture causes enhanced ammonia release, preferential hydrolyses of fats and
      proteins from the sludge macromolecular network and transformation of free fatty
      acids contained in the sludge lipids, as well as these released hydrolytically,
      to their calcium salts. The sewage sludge stabilisation with calcium hydroxide
      has no effect on homological assemblage and content of unbound stanol and sterol
      compounds in the sludge lipids and these bound into macromolecular network.
      Biogenic n-alkanes and anthropogenic linear alkylbenzenes were detected as minor
      components in the lipids and pyrolytic products from the pre-extracted cake
      residue, respectively. The alkaline agent used for the sludge stabilisation
      accelerates equilibration of the process and reduces content of pathogenic
      microorganisms.

PMID- 16620905
TI  - Photodecomposition of bisphenol A on nanometer-sized TiO2 thin film and the
      associated biological toxicity to zebrafish (Danio rerio) during and after
      photocatalysis.
AB  - We investigated the relationship between the TiO2 photocatalytic decomposition of
      bisphenol A and biological toxicity to zebrafish (Danio rerio). TiO2 particles,
      which prepared using a solvothermal method, were applied to produce a nanometer
      sized TiO2 thin film. An alcoholic solution containing the TiO2 particles and an
      inorganic binder was directly coated on the UV-lamp substrate. It was equipped in
      a photoreactor that was manufactured in our laboratory. The attachment of the
      thin TiO2 film to the UV-lamp substrate resulted in a stable and transparent
      coating. The TiO2 particles on the thin film were approximately 20-30 nm in size,
      and the resulting film thickness was approximately 200 nm after a single coat.
      The bisphenol A, which was eluted from epoxy resin in a drinking water tank, was
      completely degraded by the TiO2 photocatalysis. We initially detected
      approximately 7.8 ng/ml of bisphenol A in the epoxy-resin tank, but its
      concentration was undetectable after a 48-h photocatalytic reaction over TiO2. We
      observed a decreased survival rate in zebrafish that were reared in water exposed
      to the leaching process of the epoxy resin. After the photocatalysis, however, no
      toxic effects on the hatching rates or morphogenesis of the zebrafish were
      observed. In summary, toxicity during the TiO2 photocatalysis was observed;
      however, toxicity was no longer observed once the bisphenol A was completely
      decomposed by the TiO2 photocatalysis. On the basis of these experimental
      observations, we suggest that TiO2 photocatalysis can be adopted as a treatment
      method to purify an epoxy-resin tank.

PMID- 16620906
TI  - The potential for kelp manufacture to lead to arsenic pollution of remote
      Scottish islands.
AB  - Burning seaweed to produce kelp, valued for its high potash and soda content, was
      formerly a significant industry in remote coastal areas of Scotland and
      elsewhere. Given the high concentrations of arsenic in seaweeds, up to 100 mg kg(
      1), this study investigates the possibility that the kelp industry caused arsenic
      contamination of these pristine environments. A series of laboratory-scale
      seaweed burning experiments was conducted, and analysis of the products using
      HPLC ICP-MS shows that at least 40% of the arsenic originally in the seaweed
      could have been released into the fumes. The hypothesis that the burning process
      transforms arsenic from low toxicity arsenosugars in the original seaweeds (Fucus
      vesiculosus and Laminaria digitata) to highly toxic inorganic forms,
      predominantly arsenate, is consistent with As speciation analysis results. A
      field study conducted on Westray, Orkney, once a major centre for kelp
      production, shows that elevated arsenic levels (10.7+/-3.0 mg kg(-1), compared to
      background levels of 1.7+/-0.2 mg kg(-1)) persist in soils in the immediate
      vicinity of the kelp burning pits. A model combining results from the burning
      experiments with data from historical records demonstrates the potential for
      arsenic deposition of 47 g ha(-1) year(-1) on land adjacent to the main kelp
      burning location on Westray, and for arsenic concentrations exceeding current UK
      soil guideline values during the 50 year period of peak kelp production.

PMID- 16620907
TI  - Comparison of spatiotemporal distribution patterns of NO2 between four different
      types of air quality monitoring stations.
AB  - The concentration data of nitrogen dioxide (NO(2)), obtained from four different
      types of air quality monitoring (AQM) stations in Korea (i.e., urban traffic (A),
      urban background (B), suburban background (C), and rural background (D)), were
      explored to evaluate the fundamental facets of its distribution and behavior. As
      there are many distinctions between these four types of AQM stations, the
      observed NO(2) values were clearly distinguished from each other. It is found
      that the average NO(2) concentrations from all A stations exhibit notably high
      values within the range of 24.8 (Gwangju) to 54.6 ppb (Seoul), while those of all
      B stations change from 19.6 (Ulsan) to 34.7 ppb (Seoul). Similarly, large
      differences were also observed from NO(2) values measured between C and D type
      stations. The NO(2) values of the former were from 16.5 (Jeonbuk) to 30.2 ppb
      (Gyunggi), while the latter from 4.3 (Gyeongbuk) to 8.7 ppb (Gyunggi). Although
      their annual patterns are rather complicated to explain, the results by and large
      reflected the changes in the conditions of the surrounding environment. When the
      results are compared across seasons, most stations (A, B, and D types) tend to
      exhibit their maximum values in the winter followed by spring, fall, and summer.
      The results of this study confirm that the distribution patterns of NO(2) are
      fairly sensitive enough to reflect the basic characteristics of its source
      processes in association with such factors as the intensity of anthropogenic
      activity or population density.

PMID- 16620908
TI  - Chemical and biological characterization of dissolved organic matter from silver
      fir and beech forest soils.
AB  - Despite a growing attention to the dissolved organic matter (DOM) in terrestrial
      ecosystems and evidence of the fact that vegetation affects the quality of both
      undissolved and dissolved organic matter in soil, the role of DOM as a biological
      indicator is still poorly understood. In this work, the fertility of 59 sites,
      divided into eight key alliances of the order Fagetalia sylvaticae Pawl., was
      studied considering chemical and biological parameters such as soil DOM, hormone
      like activity, low-molecular-weight (LMW) aliphatic and phenolic acids, and
      floristic data. Both non-parametric tests and principal component analysis (PCA)
      revealed differences between silver fir and beech forests and within each type of
      forest. There were also differences between neutrophilous and acidophilous types.
      What's more, PCA reveals the dominance of the auxin (IAA)-like activity, and of
      some phenolic acids in distinguishing the acidophilous beeches (ACI) form the
      other types, whereas the gibberellin (GA)-like activity is more relevant in
      neutrophilous conditions such as thermophilous (THE) and mesophilous (MESO)
      beeches and montane (MO), high montane (HMA), high montane (HMC) silver fir
      forests. The GA-like activity is also related to the succinic, fumaric, malonic,
      and l-malic acids in the MO, HMA and HMC silver fir forests. Moreover, the role
      of LMW aliphatic acids in mobilizing the hormone-like activity, which improves
      forest growth, is stressed. The growth of seedlings of Picea abies was influenced
      by the phenolic acid content. At concentrations between 1 and 100 microM,
      phenylacetic and protocatechuic acids inhibited root growth to the same extent as
      indoleacetic acid, while p-hydroxybenzoic acid had a stimulating effect
      comparable to that of gibberellic acid. The aliphatic and phenolic acids appear
      to be related to plant strategies that influence soil fertility affecting plant
      growth through rhizodeposition. The role of LMW aliphatic and phenolic acids as
      molecular markers of ecosystem function is noted.

PMID- 16620909
TI  - 2-chlorophenol induced ROS generation in fish Carassius auratus based on the EPR
      method.
AB  - In the present study, a secondary spin trapping technique was used followed by
      electron paramagnetic resonance (EPR) analysis, to study the potential of
      reactive oxygen species (ROS) production after fish (Carassius auratus) were
      injected i.p. with different doses (50, 100, 200, 250, 500mgkg(-1)) of 2
      chlorophenol (2-CP). The ROS signal intensity of the EPR spectrum showed a
      significant increase (p<0.05, compared with the control) when the 2-CP dose was
      as low as 50mgkg(-1). There is a good relationship between the 2-CP administered
      doses and ROS generation. Based on the hyperfine splitting constants and shape of
      the EPR spectrum, the ROS which was generated in fish liver after intraperitoneal
      (i.p.) injection of 2-CP was identified as ()OH. SOD and CAT activities were
      found to be induced at lower doses of 2-CP. GSH levels fell below the control
      level following all treatments with 2-CP, and GSSG levels changed along with
      those of GSH. These observations indicated that the fish experienced oxidative
      stress. The strong positive correlation (r=0.966, p<0.005) between ()OH radical
      and lipid peroxidation suggested that lipid peroxidation was possibly induced by
      ()OH. The phase II detoxification enzyme glutathione-S-transferase (GST) may play
      an important role in 2-CP metabolism or excretion and, consequently, reduce ROS
      production. This study provides strong evidence that level of ROS is
      significantly increased in 2-CP stressed fish, and ROS may serve as a potential
      biomarker to indicate 2-CP contamination.

PMID- 16620910
TI  - Trace elements in major solid-pesticides used in the Gaza Strip.
AB  - This study describes the purity of pesticides used in Gaza in terms of trace
      elements. A semi-quantitative EMMA-XRF technique and quantitative ICP/OES was
      used to determine the concentrations of Al, As, Ba, Br, Ca, Cd, Co, Cr, Cu, Fe,
      K, Mn, Ni, Pb, Rb, Sc, Se, Sr, Ti and Zn in 50 of the most commonly used solid
      pesticides collected from the five central shops in the Gaza Strip. The results
      revealed that the pesticides contain considerable amounts of trace elements and
      do not comply with the expected-theoretical structure of each species. Moreover,
      they do not reflect the actual constituents mentioned in the trade labels.
      Interviews with market owners and field surveys confirmed that the pesticides
      were not pure. In some cases they have been mixed in local markets with minor
      inorganic species without a scientific basis. They may also have been smuggled
      into Gaza with differing impurities. The results indicate that pesticides should
      be considered as a source of certain trace metals (particularly Cu, Mn and Zn)
      and other elements (Br, Sr and Ti), which may affect their mass balances in soil
      and groundwater as well as their plant uptake. Different scenarios and
      calculation models of the transport of trace elements in soil and groundwater of
      the Gaza Strip should include pesticides as an additional source.

PMID- 16620911
TI  - Rapid and complete dechlorination of PCP in aqueous solution using Ni-Fe
      nanoparticles under assistance of ultrasound.
AB  - The Ni-Fe bimetallic particles have been laboratory prepared using sodium
      borohydride (NaBH4) as the reductant to reduce Ni2+ and Fe2+ in aqueous solution
      simultaneously, and characterized by TEM, XRD, BET and XPS. The particles were
      proved to be nanoscale amorphous alloy with an average diameter of about 30 nm
      and a BET surface area of 20.9 m2 g(-1). Experiments for dechlorination of
      pentachlorophenol (PCP) by the Ni-Fe bimetallic nanoscale particles in aqueous
      solutions were carried out under the enhancement of ultrasound. Major factors
      that influence the dechlorination efficiency, such as initial pH value, Ni
      content in the Ni-Fe particles, and output power of ultrasonic irradiation, were
      investigated. The results indicated that Ni-Fe nanoscale bimetallic particles
      were very effective for the dechlorination of PCP. Dechlorination efficiency was
      46% in 30 min under the optimal condition without assistance of ultrasound,
      whereas it increased to 96% when ultrasonic irradiation was present. Initial pH
      value showed apparent effect on the dechlorination. As the pH varied from acidic
      condition to neutral condition, the dechlorination efficiency decreased
      dramatically. In addition, the dechlorination efficiency was improved with
      increased Ni/Fe ratio and ultrasonic output power. Less chlorinated phenols
      including tetrachlorophenol, trichlorophenol, dichlorophenol, monochlorophenol
      were formed during the initial reaction, and phenol was determined by GC-MS as
      sole product in the end of reaction.

PMID- 16620912
TI  - Effects of activity pattern on eye size and orbital aperture size in primates.
AB  - Among primates, nocturnal species exhibit relatively larger orbital apertures
      than diurnal species. Most researchers have considered this disparity in orbital
      aperture size to reflect differences in eye size, with nocturnal primates having
      relatively large eyes in order to maximize visual sensitivity. Presumed changes
      in eye size due to shifts in activity pattern are an integral part of theoretical
      explanations for many derived features of anthropoids, including highly
      convergent orbits and a postorbital septum. Here I show that despite clear
      differences in relative orbital aperture size, many diurnal and nocturnal
      primates do not differ in relative eye size. Among nocturnal primates, relative
      eye size is influenced by diet. Nocturnal visual predators (e.g., Tarsius, Loris,
      and Galago moholi) tend to have larger relative eye sizes than diurnal primates.
      By contrast, nocturnal frugivores (e.g., Perodicticus, Nycticebus, and
      Cheirogaleus) have relative eye sizes that are comparable to those of diurnal
      primates. Although some variation in orbital aperture size can be attributed to
      variation in eye size, both cornea size and orbit orientation also exert a strong
      influence on orbital aperture size. These findings argue for caution in the use
      of relative orbital aperture size as an indicator of activity pattern in fossil
      primates. These findings further suggest that existing scenarios for the
      evolution of unique orbital morphologies in anthropoids must be modified to
      reflect the importance of ecological variables other than activity pattern.

PMID- 16620913
TI  - A fossil hominoid proximal femur from Kikorongo Crater, southwestern Uganda.
AB  - The external morphology of a fragmentary right proximal femur from southwestern
      Uganda is described here. Discovered in the Kikorongo Crater of Queen Elizabeth
      National Park in 1961, this specimen was informally assigned to Homo sapiens
      (although never described) and tentatively dated to the late Pleistocene.
      However, because aspects of the external morphology of the femur align the fossil
      with the African great apes, we suggest that the Kikorongo femur may be the first
      postcranial fossil of the genus Pan. Like the African apes, the Kikorongo
      specimen lacks both an obturator externus groove and an intertrochanteric line.
      It has a short femoral neck with a circular cross section, and a narrow and deep
      superior notch. Using resampling statistics and discriminant function analysis,
      the Kikorongo femur clustered with the genus Pan, as opposed to Gorilla or Homo.
      However, if the specimen is from Pan, it would be large for this taxon.
      Furthermore, features that clearly distinguish the external morphology of Plio
      Pleistocene hominin proximal femora from African ape femora, such as the shape of
      the femoral neck in cross section and femoral neck length, have converged in
      Holocene humans and African apes. Unfortunately, the internal morphology of the
      femoral neck of the Kikorongo fossil was not discernable. Although we hypothesize
      that the Kikorongo femur is from the genus Pan, there is such variability in the
      proximal femora of modern humans that, although it would be an unusual human, it
      remains possible that this fossil represents H. sapiens.

PMID- 16620914
TI  - Interspecific and intraspecific relationships between tooth size and jaw size in
      primates.
AB  - The association between mandibular robusticity, postcanine megadontia, and canine
      reduction in hominins has led to speculation that large and robust jaws might be
      required to spatially accommodate large canine and molar teeth in hominins and
      other primates. If so, then variations in mandibular form that are generally
      regarded as biomechanical adaptations to masticatory demands might instead be
      incidental effects of functional requirements of tooth support. While the
      association between large teeth and deep, robust jaws in hominins is well known,
      the relationship between tooth size and jaw size has not been systematically
      evaluated in a comparative sample of primates. We evaluate the relationships
      between molar tooth size, canine tooth size, and mandibular corpus and symphyseal
      dimensions in a sample of adult anthropoids in interspecific (n=84 species) and
      intraspecific (n=36 species) contexts. For intraspecific comparisons, tooth size
      and jaw size are correlated, but for a majority of species this is a function of
      sexual size dimorphism. Interspecific comparisons lend little direct support to
      the hypothesis that jaw breadth directly covaries with molar tooth breadth, but
      they do support the hypothesis that mandibular depth is associated with canine
      tooth size in males. The latter observation suggests that if there is a causal
      association between canine size and mandibular depth, it is subject to a
      threshold effect. In contrast, neither corpus nor symphyseal robusticity,
      measured as a shape index of breadth/height, are correlated with tooth size. Our
      results suggest that further studies of the relationship between tooth size and
      corpus morphology should focus on tooth root size and corpus bony architecture,
      and that species-specific factors should have a strong impact on such
      relationships.

PMID- 16620915
TI  - Role of INK4a locus in normal eye development and cataract genesis.
AB  - The murine INK4a locus encodes the critical tumor suppressor proteins, p16(INK4a)
      and p19(ARF). Mice lacking both p16(INK4a) and p19(ARF) (INK4a-/-) in their
      FVB/NJ genetic backgrounds developed cataracts and microophthalmia.
      Histopathologically, INK4a-/- mice showed defects in the developmental regression
      of the hyaloid vascular system (HVS), retinal dysplasia, and cataracts with
      numerous vacuolations, closely resembling human persistent hyperplastic primary
      vitreous (PHPV). Ocular defects, such as retinal fold and abnormal migration of
      lens fiber cells, were observed as early as embryonic day (E) 15.5, thereby
      resulting in the abnormal differentiation of the lens. We also found that ectopic
      expression of p16(INK4a) resulted in the induction of gammaF-crystallin,
      suggesting an important role of INK4a locus during mouse eye development, and
      also providing insights into the potential genetic basis of human cataract
      genesis.

PMID- 16620916
TI  - Changes in dopamine levels and locomotor activity in response to selection on
      virgin lifespan in Drosophila melanogaster.
AB  - Among various other mechanisms, genetic differences in the production of reactive
      oxygen species are thought to underlie genetic variation for longevity. Here we
      report on possible changes in ROS production related processes in response to
      selection for divergent virgin lifespan in Drosophila. The selection lines were
      observed to differ significantly in dopamine levels and melanin pigmentation,
      which is associated with dopamine levels at eclosion. These findings confirm that
      variation in dopamine levels is associated with genetic variation for longevity.
      Dopamine has previously been implied in ROS production and in the occurrence of
      age-related neurodegenerative diseases. In addition, we propose a possible
      proximate mechanism by which dopamine levels affect longevity in Drosophila: We
      tested if increased dopamine levels were associated with a "rate-of-living"
      syndrome of increased activity and respiration levels, thus aggravating the level
      of oxidative stress. Findings on locomotor activity and oxygen consumption of
      short-lived flies were in line with expectations. However, the relation is not
      straightforward, as flies of the long-lived lines did not show any consistent
      differences in pigmentation or dopamine levels with respect to the control lines.
      Moreover, long-lived flies also had increased locomotor activity, but showed no
      consistent differences in respiration rate. This strongly suggests that the
      response for increased and decreased lifespan may be obtained by different
      mechanisms.

PMID- 16620917
TI  - Extended longevity of wild-derived mice is associated with peroxidation-resistant
      membranes.
AB  - Two lines of mice, Idaho (Id) and Majuro (Ma), both derived from wild-trapped
      progenitors, have previously been shown to have extended lifespans in captivity
      when compared to a genetically heterogenous laboratory line of mice (DC). We have
      examined whether membrane fatty composition varies with lifespan within the
      species Mus musculus in a similar manner to that previously demonstrated between
      mammal species. Muscle and liver phospholipids from these long-living mice lines
      have a reduced amount of the highly polyunsaturated omega-3 docosahexaenoic acid
      compared to the DC mice, and consequently their membranes are less likely to
      peroxidative damage. The relationship between maximum longevity and membrane
      peroxidation index is similar for these mice lines as previously observed for
      mammals in general. It is suggested that peroxidation-resistant membranes may be
      an important component of extended longevity.

PMID- 16620918
TI  - In vivo brain microdialysis studies on the striatal dopamine and serotonin
      release in zitter mutant rats.
AB  - In the present study, using in vivo brain microdialysis, we investigated the
      basal extracellular dopamine (DA) and serotonin (5-HT) release in the caudal
      striatum (cSTR) of young (4-6 months old) and aged (10-12 months old) zitter
      mutant rats. The basal extracellular levels of DA release in both young and aged
      zitter rats were significantly lower than that of age-matched Sprague-Dawley (SD)
      rats, whereas only aged zitter rats showed a significant difference in the basal
      5-HT release. Dopaminergic neurons were more vulnerable than serotonergic neurons
      in the cSTR of zitter mutant rats during aging. Perfusion of 60 mM potassium (K+)
      enhanced the extracellular levels of cSTR DA in the young zitter rats and the
      extracellular levels of both DA and 5-HT in the cSTR of the aged zitter rats. The
      firing rate of K+-stimulated monoamine release in the cSTR was significantly
      higher in the zitter rats than in the age-matched SD rats. These findings suggest
      that there are innate quantitative differences in the releasable pool and the
      availability of monoamines in the cSTR of zitter mutant rats.

PMID- 16620919
TI  - Expression of RAB27B is up-regulated in senescent human cells.
AB  - Immortal SVts8 cells that express thermolabile SV40 T antigen exhibit a
      senescence-like phenomenon upon inactivation of the T antigen. By using a cDNA
      subtractive hybridization technique, RAB27B, a member of the RAB GTPase family,
      was found to be up-regulated in senescent SVts8 cells. The up-regulation of
      RAB27B depends on the p53 gene. Enhanced expression was also observed in
      replicative senescence in normal human fibroblasts.

PMID- 16620921
TI  - Potential protection of skin by acute UVA irradiation--from cellular to animal
      models.
AB  - The UVA (320-380 nm) component of sunlight has oxidizing properties which may be
      deleterious to skin cells and tissue but can also lead to the strong up
      regulation of the heme-catabolizing enzyme, heme oxygenase-1. This enzyme has
      well-established antioxidant actions in cells as well as anti-inflammatory
      properties in mammals. There is also evidence from rodent models that this enzyme
      is responsible for the UVA-mediated protection against UVB-induced
      immunosuppression that occurs in skin. The relevance of these findings to acute
      and chronic effects of sunlight including skin carcinogenesis is currently under
      investigation as are the potential implications for sunlight protection in
      humans.

PMID- 16620920
TI  - Renal failure causes early death of bcl-2 deficient mice.
AB  - BCL-2 functions as a death repressor molecule in an evolutionary conserved cell
      death pathway. Inactivation of bcl-2 in mice results in pleiotropic effects
      including postnatal growth retardation, massive apoptosis in lymphoid tissues,
      polycystic kidney disease (PKD) and shortened lifespan. To evaluate the influence
      of the affected bcl-2 deficient kidneys on the postnatal development and lifespan
      of bcl-2 knockout mice we used "the rescue of (n-1) affected tissues" strategy.
      According to this strategy bcl-2 heterozygous animals were crossed with H2K-hbcl
      2 transgenic mice expressing human BCL-2 in most tissues and organs excluding the
      kidney. Overexpression of hBCL-2 in bcl-2-/- mice rescues growth retardation,
      normalizes and protects the hematolymphoid system from gamma-radiation. However,
      the hbcl-2 transgene is not expressed in kidneys and the rescued mice have PKD
      and a shortened lifespan. Thus, our results indicated that PKD is the main reason
      of early mortality in bcl-2 deficient mice. Moreover, we have created mouse
      model, similar to the kidney specific knockout of bcl-2. Such models can be
      useful to study the influence of bcl-2 or other gene deficiency in individual
      organs (or tissues) on development and ageing of whole organism.

PMID- 16620922
TI  - Endocrine and behavioral observations during transition of non-breeding into
      breeding season in female American bison (Bison bison).
AB  - This study provides endocrine data in relation to behavioral events during the
      transition of the non-breeding into the breeding season in American bison (Bison
      bison). Fecal progesterone metabolite patterns (20-oxo-P) were obtained in 13
      adult female American bison and hormonal data were correlated with behavioral
      observations; i.e. copulation, male tending, female tail-up behavior and
      gestation length. Based on fecal progesterone metabolite patterns, the breeding
      season started between the middle of July and early August. Predictable short
      cycles reflected the transition from non-breeding to the breeding season; the
      luteal phase of these cycles was 4.10+/-0.86 days. Copulations and female tail-up
      behavior were reliably associated with the hormonally detected ovulation. Male
      tending behavior was more loosely associated with hormonally detected ovulation.
      The observed hormonal pattern in the study females indicated that 9 of 10
      pregnant cows conceived during the second ovulatory period in the breeding
      season. One other cow conceived during her third ovulatory period, and one cow
      did not conceive until later in the breeding season by beginning of October.
      Gestation duration was on average 266.30+/-1.00 days. In summary, this study
      confirmed that the bison is a seasonally polyestrous species; the transition from
      the non-breeding into the breeding season was characterized by short cycles with
      low progesterone metabolite values.

PMID- 16620923
TI  - Comparison of equilibration times when freezing epididymal sperm from African
      buffalo (Syncerus caffer) using Triladyl or AndroMed.
AB  - Because of risks of disease transmission, it is not possible to move African
      buffalo (Syncerus caffer) within South Africa. Therefore, new ways must be found
      to enable exchange of genetic material and to increase genetic diversity. In this
      study epididymal sperm from 11 African buffaloes was exposed to 8 different pre
      freezing equilibration times, using 2 different semen extenders. To test the
      influence of equilibration time and to find a practical way of freezing sperm in
      the field equilibration times between 2 and 9 h were compared. The extenders used
      were Triladyl and the totally defined extender AndroMed (both Minitub,
      Tiefenbach, Germany). Post-thaw motility, longevity and acrosomal integrity were
      compared. Different equilibration times did not result in different post-thaw
      qualities. The use of Triladyl resulted almost always in higher post-thaw
      motilities and in better acrosomal integrity. Individual bulls had a significant
      influence on measured parameters. Results indicate that sperm flushed in the
      field can be stored in freezing medium for up to 9 h before being further
      processed and that Triladyl is superior to AndroMed when freezing epididymal
      African buffalo sperm. This knowledge is important to plan fieldwork, since
      working conditions are usually far from the ideal of a laboratory.

PMID- 16620924
TI  - Influence of staining and sampling procedures on goat sperm morphometry using the
      Sperm Class Analyzer.
AB  - Computer-assisted sperm morphometry analysis (ASMA) has improved the assessment
      of sperm morphology, but the results depend on the use of adequate sampling and
      staining procedures of spermatozoa from individual species. In this study, the
      Sperm Class Analyzer ASMA system was used for the morphometric analysis of goat
      sperm heads. Semen samples, obtained from four bucks, were used to evaluate the
      influence of three staining procedures (Diff-Quik, Hemacolor and Harris'
      Haematoxylin) on the accuracy of image processing and sperm morphometry, the
      effect of the number of cells analysed and the repeatability of the method. These
      experiments were performed to obtain objective, accurate and reliable sperm
      morphometric measurements of goat spermatozoa. Diff-Quik and Harris' Haematoxylin
      were significantly (p<0.05) more accurate than Hemacolor. However, Diff-Quik
      obtained the highest proportion of correctly analysed sperm heads (86.06%) and
      the lowest coefficients of variation on the image processing and morphometric
      measurements. The staining methods affected significantly the sperm dimensions
      (p<0.001) with increased values from Diff-Quik than Hemacolor and Harris'
      Haematoxylin, respectively (Diff-Quik>Hemacolor>Harris' Haematoxylin). No
      differences in morphometric parameters were found when 100, 150, 175 or 200
      spermatozoa were analysed. The repeatability of results obtained was very high
      since no differences were found when measuring the same sperm on multiple
      attempts. In conclusion, to obtain objective, accurate and repeatable sperm
      morphometric measurements by the Sperm Class Analyzer system in goats, the
      analysis of 100 spermatozoa from slides which have been previously stained with
      Diff-Quik is recommended.

PMID- 16620925
TI  - A pilot study on post-thawing quality of Iberian red deer spermatozoa (epididymal
      and electroejaculated) depending on glycerol concentration and extender
      osmolality.
AB  - The optimization of cryopreservation extenders is a fundamental issue for
      adequately performing germplasm banking on wild species. We have tested two
      glycerol concentrations (4 and 8%), and three extender osmolalities (320, 380 and
      430 mOsm/kg; before adding cryoprotectants), for cryopreservation of epididymal
      and ejaculated sperm samples from Iberian red deer. All the extenders were based
      on Tes-Tris and fructose (for osmolality adjustment), and complemented with 20%
      egg yolk. Epididymal and ejaculated sperm samples were obtained from the cauda
      epididymis (post-mortem) and using electroejaculation, respectively. Samples were
      diluted 1:1 with each extender and equilibrated for 2 h at 5 degrees C. Then,
      they were diluted down to 100x10(6) sperm/mL and frozen at -20 degrees C/min.
      Post-thawed samples were assessed for motility (CASA), HOS test, proportion of
      swollen (osmotically challenged) cells in the untreated sample, viability and
      acrosomal status. For epididymal samples, 8% glycerol rendered a slightly higher
      proportion of intact acrosomes on viable spermatozoa than 4%; regarding extender
      osmolality, 380 and 430 mOsm/kg rendered higher motility results, and the 430
      mOsm/kg yielded the lowest proportion of swollen spermatozoa. For ejaculated
      samples, 4% glycerol yielded more viable spermatozoa than 8%; for extender
      osmolality, 320 mOsm/kg rendered the highest percentages of progressively motile
      and viable spermatozoa, although 380 mOsm/kg extender was not significantly
      different. These results show that sample source influences extender suitability,
      and that extenders should be isoosmotic or rather slightly hyperosmotic. Future
      studies should test multiple glycerol concentrations and extender osmolalities in
      order to adjust them to these kinds of sample.

PMID- 16620926
TI  - A model for cystic endometrial hyperplasia/pyometra complex in the bitch.
AB  - The objective of this study was to develop a reliable model for the study of the
      cystic endometrial hyperplasia and pyometra complex (CEH/P) in the bitch.
      Greyhound bitches (n = 15) were ovariectomised and allocated into three groups
      (Group 1, n = 5; Group 2, n = 5; Group 3, n = 10, including 5 used from Group 1).
      Simulated proestrus, estrus and diestrus were induced by treatment with estradiol
      benzoate and megestrol acetate. The duration of cervical opening during estrus
      was determined by the intra-vaginal infusion of radio-opaque medium and
      subsequent radiography of the uterus (Group 1). One milliliter of a culture of
      Escherichia coli (with five uro-pathogenic virulence factors as identified by
      PCR: pap, sfa, hlyA, cnf1 and fim) was inoculated intra-vaginally daily
      throughout the simulated estrus (Group 2). One milliliter of the culture (n = 6)
      or sterile Luria-Bertani broth (n = 4) was introduced directly into the uterus on
      simulated diestrus Days 8 or 12 (Group 3). Necropsies were performed 12 and 7-14
      days after the inoculation (Groups 2 and 3). The cervix remained open throughout
      the duration of simulated estrus (5-6 days) in four out of five bitches, and for
      a shorter duration (3 days of a 6-day estrus period) in one bitch (Group 1).
      CEH/P was induced by inoculation of bacteria into the uterus (10/10 bitches) but
      not into the vagina (0/5 bitches), (P = 0.003). A model for the study of CEH/P
      has been validated.

PMID- 16620927
TI  - Nuclear transfer in cats and its application.
AB  - Nuclear transfer (NT) technology is typically used for generating identical
      individuals, but it is also a powerful resource for understanding the cellular
      and molecular aspects of nuclear reprogramming. Most recently, the procedure has
      been used in humans for producing patient-specific embryonic stem cells. The
      successful application of NT in cats was demonstrated by the birth of domestic
      and non-domestic cloned kittens at a similar level of efficiency to that reported
      for other mammalian species. In cats, it has been demonstrated that either in
      vivo or in vitro matured oocytes can be used as donor cytoplasts. The length of
      in vitro oocyte maturation affects in vitro development of reconstructed embryos,
      and oocytes matured in vitro for shorter periods of time are the preferred source
      of donor cytoplasts. For NT, cat somatic cells can be synchronized into the G0/G1
      phase of the cell cycle by using different methods of cell synchronization
      without affecting the frequency of in vitro development of cloned embryos. Also,
      embryo development to the blastocyst stage in vitro is not influenced by cell
      type, but the effect of cell type on the percentage of normal offspring produced
      requires evaluation. Inter-species NT has potential application for preserving
      endangered felids, as live offspring of male and female African wildcats (AWC,
      Felis silvestris lybica) have been born and pregnancies have been produced after
      transferring black-footed cat (Felis nigripes) cloned embryos into domestic cat
      (Felis silvestris catus) recipients. Also, successful in vitro embryo development
      to the blastocyst stage has been achieved after inter-generic NT of somatic cells
      of non-domestic felids into domestic cat oocytes, but no viable progeny have been
      obtained. Thus, while cat cytoplasm induces early nuclear remodeling of cell
      nuclei from a different genus, the high incidence of early embryo developmental
      arrest may be caused by abnormal nuclear reprogramming. Fetal resorption and
      abortions were frequently observed at various stages of pregnancy after transfer
      of AWC cloned embryos into domestic cat recipients. Abnormalities, such as
      abdominal organ exteriorization and respiratory failure and septicemia were the
      main causes of death in neonatal cloned kittens. Nonetheless, several live
      domestic and AWC cloned kittens have been born that are seemingly normal and
      healthy. It is important to continue evaluating these animals throughout their
      lives and to examine their capability for natural reproduction.

PMID- 16620928
TI  - Sperm maturation in the domestic cat.
AB  - The epididymis is essential for sperm development and maturation, and,
      subsequently, the ability of spermatozoa to penetrate and fertilize the female
      gamete. Functional differences in segments of the long tubule are reflected by
      histological differences among epididymal regions. The feline epididymis can be
      divided into six different regions according to their histological differences. A
      marked increase in sperm concentration occurs between regions 2 and 3, indicating
      resorption of fluid in region 2, a concept supported by the histological
      characteristics of the epithelium. At the transition between regions 4 and 5,
      located between the caput and corpus epididymides, histological characteristics
      change from being that of a maturation function to being typical of a storage
      function. Migration of the cytoplasmic droplet and induction of motility occur in
      this same region. Proteins are secreted from epithelial cells in the feline
      epididymis by merocrine and apocrine secretion, although the functions of
      different feline epididymal proteins have not been determined. Hypotaurine,
      taurine and, probably, alkaline phosphatase are produced by the feline
      epididymis. During epididymal transit the percentage of immature, unviable and
      morphologically abnormal spermatozoa decreases, indicating the existence of a
      mechanism that removes abnormal spermatozoa. In contrast, the percentage of
      spermatozoa with abnormal tails increases slightly during epididymal transit.
      Most of the distal droplets present on spermatozoa in the cauda epididymis are
      lost at or after ejaculation. Additional knowledge of the feline epididymis
      should be beneficial for developing sperm preservation protocols and advance the
      prospects for effective male contraceptive methods.

PMID- 16620929
TI  - Surfactant protein A and D in the reproductive tract of stallion.
AB  - The presence of surface-active material in the lung alveolus has been known for
      several decades as being essential for normal lung function. The host defense and
      controlling inflammatory processes of the lung are the major functions of SP-A
      and SP-D. SP-A and SP-D were originally demonstrated in alveolar type II cells,
      but recent studies have shown extrapulmonary expression of SP-A and SP-D
      indicating systemic roles of these proteins. Present study describes the presence
      of SP-A and SP-D in the stallion genital tract, prepuce, prostate, testis, and
      seminal vesicle using Western blotting and immunohistochemistry. This paper
      presents the first evidence for the existence of SP-A and SP-D glycoproteins in
      the stallion genital tract. We examined genital system organs and tissues from
      stallion and were able to show that surfactant protein A and D reactive with
      surfactant-specific antibodies were present in the stallion genital tract tissues
      and organs. On the basis of results, it can be postulated that surfactant
      proteins in the stallion reproductive tract contribute to the immune surveillance
      and to active barrier defense mechanism.

PMID- 16620930
TI  - The application of in vitro sperm competition test to evaluate the impact of ZP
      derived peptides on fertilization capacity of cat sperm.
AB  - The present study aimed to establish a sensitive in vitro assay to assess the
      binding capacity of cat spermatozoa. Cat oocytes and epididymal sperm cells were
      isolated from gonads and cultured for in vitro fertilization. Before
      fertilization, the sperm cells were incubated either in 10 microM green dye Fluo
      3-AM or 10 microM orange dye CellTracker Orange CMTMR (Molecular Probes),
      respectively. After removing the dyes by washing, sperm cells stained with each
      dye were added to medium drops containing oocytes in various proportions and
      cultured for 16 h at 37 degrees C, 5% CO(2). The oocytes were examined using
      fluorescence microscopy. Sperm bound to oocytes, and stained with different
      colors, were counted. When fresh epididymal sperm were mixed in at a specific
      proportion, the number of sperm bound to the zona pellucida (ZP) of oocytes
      reflected the proportion of differently colored sperm in the medium. This
      indicated that neither dye influenced the binding capacity of cat sperm. Mixing
      fresh and cryopreserved sperm, however, resulted in a higher number of fresh
      sperm bound to the oocyte surface in comparison to frozen-thawed sperm. Also, the
      pre-incubation of cat sperm cells with ZP derived peptide reduced the sperm
      binding capacity by 40%. In conclusion, the presented sperm competition assay
      allows assessment of fertilizing capacity of cat spermatozoa in vitro when a
      mixture of two different populations is used. The applied supravital fluorescence
      dyes do not affect motility and binding capacity of sperm cells and were clearly
      distinguishable under fluorescence microscopy. We demonstrate that the assay can
      be used to study the impact of sperm treatment, such as cryopreservation or pre
      incubation in bioactive peptides, on fertilizing capacity.

PMID- 16620931
TI  - Folliculogenesis in the domestic cat (Felis catus).
AB  - The dynamic regulation of mammalian folliculogenesis is a key component of the
      reproductive process. Traditionally, the rodent had been used as a model to study
      ovarian function and reproductive physiology due to the availability of animals,
      their relatively short cycle length, high rate of fecundity and short generation
      interval. We maintain that much basic information can be determined using
      domestic cat ovaries retrieved from local veterinary clinics following routine
      spaying, without having the expense of maintaining a colony of laboratory cats.
      Studies of normal feline reproductive physiology and advances in reproductive
      technology may be extrapolated for use in endangered non-domestic felids.
      Increased understanding of feline reproduction will be beneficial to veterinary
      medicine, and to groups working to control feral cat populations. It is important
      to examine reproductive mechanisms in alternative animal models as there are a
      vast number of threatened and endangered species in which we lack the critical
      reproductive information needed to assist in preserving their long-term survival.

PMID- 16620932
TI  - Effect of co-culturing with embryonic fibroblasts on IVM, IVF and IVC of canine
      oocytes.
AB  - We studied the effects of mouse embryonic fibroblasts (MEF) and canine embryonic
      fibroblasts (CEF) on IVM, IVF and IVC of canine oocytes. Cumulus-oocyte complexes
      were harvested from ovaries by slicing, and in vitro maturation was evaluated in
      three different conditions: culture media only (control), co-culture with MEF, or
      co-culture with CEF. The oocytes were cultured for 48 or 72 h. Only oocytes
      larger than 100 microm in diameter with a homogeneous dark cytoplasm and two or
      more layers of cumulus cells were used. The culture medium was TCM 199+10% fetal
      bovine serum (FBS) with 100 IU/mL penicillin and 100 microg/mL streptomycin.
      After 48 h of IVM, the oocytes were fertilized in vitro with fresh canine
      spermatozoa that had been selected by a swim-up method, and the oocytes and
      spermatozoa were co-cultured in modified Krebs-Ringer bicarbonate solution (TYH)
      for up to 20 h in 5% CO2 in air at 38.5 degrees C. After insemination, oocytes
      were transferred to three different conditions (the same as for IVM) and were
      cultured. After 48 or 72 h of maturation in vitro, the maturation rate of MII
      oocytes cultured in co-culture of MEF and CEF was higher than for oocytes
      cultured in control (P<0.05). Although the rate that reached the MII stage was
      not different in the 48 and 72 h cultures, the percentage of degenerated oocytes
      was greater at 72 h in all three treatment groups. The proportion of monospermic
      and polyspermic oocytes was not different among the three treatment groups.
      Cleavage rates were higher in the MEF and CEF treatment groups than in the
      control group (P<0.05). Co-culture with CEF developed the embryo up to the 16
      cell stage, and with MEF up to morula stage. In conclusion, co-culture of
      embryonic fibroblast cells enhanced nuclear and cytoplasmic maturation of canine
      oocytes.

PMID- 16620933
TI  - Comparative endocrinology of domestic and nondomestic felids.
AB  - The ability to track gonadal and adrenal activity via hormones is key to
      optimizing health and reproduction. Through decades of study, a great deal has
      been learned about the biology of female domestic cats, including endocrine
      function. More recently, comparative endocrine studies have greatly expanded our
      knowledge base of nondomestic felids as well. The latter has been possible
      largely through the development of noninvasive fecal steroid metabolite analysis
      techniques, which currently is the method of choice for monitoring endocrine
      function in wildlife species, including felids. It now is well-recognized that a
      range in endocrine patterns exists among Felidae, with many traits and mechanisms
      being uncommon, if not unique. There is a high degree of variability in the type
      of ovulation (spontaneous versus induced) expressed across the taxon. Even within
      species, some individuals exhibit ovulation that is only induced, whereas others
      ovulate spontaneously as well. Steroid metabolism also differs in that
      metabolites are excreted almost exclusively in feces, with very little steroid
      found in urine. Across species there are marked differences in seasonal and
      social influences on reproduction, adrenal responses to husbandry practices, and
      ovarian responses to assisted reproductive procedures. This means that developing
      strategies to improve health and reproduction of felids must be done on a species
      by species basis. This paper summarizes current knowledge on the reproductive
      endocrinology of female domestic and nondomestic cats, and describes how the
      rapidly growing endocrine database is aiding ex situ management efforts.

PMID- 16620934
TI  - Long-term cryopreservation of mouse sperm.
AB  - The objective was to determine if mouse sperm can maintain their fertilizing
      ability after being frozen for >10 y and whether the offspring derived from these
      sperm had normal fertilizing ability and phenotype. We cryopreserved sperm from
      six strains of mice (C57BL/6J, DBA/2N, BALB/cA, C3H/HeJ, B6D2F1 and B6C3F1) in a
      solution containing 18% (w/v) raffinose and 3% (w/v) skim milk, and preserved
      them in liquid nitrogen for >10 y. To assess the normality and fertilizing
      ability of these sperms, they were thawed and used for in vitro fertilization of
      oocytes of the same strains. Fertilization rates for C57BL/6J, DBA/2N, BALB/cA,
      C3H/HeJ, B6D2F1 and B6C3F1 were 66.4, 92.3, 72.8, 32.9, 60.3 and 53.7%,
      respectively. Furthermore, 38.3, 15.0, 43.3, 26.1, 38.3 and 16.7% of the embryos
      transferred to pseudopregnant females developed and produced live offspring that
      had normal phenotype and fertility.

PMID- 16620935
TI  - Vitrification of bovine oocytes after treatment with cholesterol-loaded methyl
      beta-cyclodextrin.
AB  - A major site of cryoinjury during cryopreservation of mammalian oocytes is the
      plasma membrane. Chilling can irreversibly damage plasma membrane integrity
      during the lipid phase transition that occurs upon cooling. Membranes containing
      higher cholesterol concentrations are more fluid at lower temperatures and
      therefore less sensitive to cooling. The purpose of this study was to determine
      if cryosurvival of vitrified oocytes could be improved by incubation with
      cholesterol-loaded methyl-beta-cyclodextrin (CLC) prior to vitrification in the
      presence or absence of fetal calf serum (FCS), and if cholesterol could enter
      oocytes through cumulus cells and the zona pellucida. Cumulus-enclosed oocytes
      incubated with various concentrations (0, 0.75 or 1.5 mg/mL) of CLC in the
      presence of FCS for 25-45 min prior to vitrification did not result in different
      rates of development after warming of vitrified oocytes, followed by in vitro
      fertilization. However, there was an increase (P<0.05) in cleavage and number of
      eight-cell embryos from oocytes preincubated for 1h with 2mg/mL CLC in a
      chemically defined system and then handled and vitrified in chemically defined
      media, in comparison to those not exposed to CLC prior to vitrification or to
      those handled and vitrified in the presence of FCS (55, 41 and 38% eight-cell
      embryos, respectively). Fluorescence was seen in cumulus-oocyte complexes (COCs)
      previously exposed to CLC containing cholesterol labeled with a fluorescent dye;
      fluorescence was also seen in oocytes after removal of the cumulus cells. Oocytes
      not exposed to the labeled cholesterol did not fluoresce. Cholesterol from CLC
      readily entered cumulus cells and oocytes and improved survival in chemically
      defined vitrification systems.

PMID- 16620936
TI  - Preservation of female germ cells from ovaries of cat species.
AB  - This review provides an overview on recent knowledge on female germ cell
      population within cat ovaries; on isolation, culture and cryopreservation of
      feline preantral follicles and on ovarian tissue preservation.

PMID- 16620937
TI  - Gamete cryopreservation in the domestic cat.
AB  - Cryopreservation of gametes is an important tool for the improvement of assisted
      reproductive technologies. In-depth studies of spermatozoon and oocyte
      characteristics are required in order to define efficient protocols for the
      maintenance of viability, including fertilizing and developmental ability, of
      gametes after thawing. In the domestic cat, semen cryopreservation techniques
      still produce variable results, the cryopreservation of oocytes is at an
      experimental level and there have been only a few attempts at cryopreserving
      gonadal tissue. However, each procedure has generated promising results and has
      important implications, both for improving reproductive performance of valuable
      breeds of domestic cats and for conservation of biodiversity in endangered felids
      by reclamation of valuable male and female germplasm.

PMID- 16620938
TI  - Detection of ovine lentivirus in the cumulus cells, but not in the oocytes or
      follicular fluid, of naturally infected sheep.
AB  - The aim of this study was to examine the Maedi-Visna virus (MVV) infection status
      of oocytes, cumulus cells, and follicular fluid taken from 140 ewes from breeding
      flocks. MVV proviral-DNA and MVV RNA were detected using nested-PCR and RT-PCR
      MVV gene amplification, respectively in the gag gene. Nested-PCR analysis for MVV
      proviral-DNA was positive in peripheral blood mononuclear cells in 37.1% (52/140)
      of ewes and in 44.6% (125/280) of ovarian cortex samples. The examination of
      samples taken from ovarian follicles demonstrated that 8/280 batches of cumulus
      cells contained MVV proviral-DNA, whereas none of the 280 batches of oocytes
      taken from the same ovaries and whose cumulus cells has been removed, was found
      to be PCR positive. This was confirmed by RT-PCR analysis showing no MVV-viral
      RNA detection in all batches of oocytes without cumulus cells (0/280) and
      follicular fluid samples taken from the last 88 ovaries (0/88). The purity of the
      oocyte fraction and the efficacy of cumulus cell removal from oocytes was proved
      by absence of granulosa cell-specific mRNA in all batches of oocytes lacking the
      cumulus cells, using RT-PCR. This is the first demonstration that ewe cumulus
      cells harbor MVV genome and despite being in contact with these infected-cumulus
      cells, the oocytes and follicular fluid remain free from infection. In addition,
      the enzymatic and mechanical procedures we used to remove infected-cumulus cells
      surrounding the oocytes, are effective to generate MVV free-oocytes from MVV
      infected ewes.

PMID- 16620939
TI  - Evaluation of methodology for administration of porcine FSH for use in estrus
      induction and for increasing ovulation rate in prepubertal gilts.
AB  - Ovulation rate influences production efficiency of oocytes and embryos and
      depends upon the amount of gonadotropin administered and the ratio of FSH:LH
      activity. In Experiment 1, gilts (n=135) were assigned to receive 10 or 15 Armour
      units (AU) of porcine FSH containing 6%, 10%, or 15% LH, whereas controls
      received PG600. Gilts received 1/6th the FSH dose in six sc administrations at 8
      h intervals. There was no treatment effect on incidence of estrus (66%) or cysts
      (23.9%), or number of corpora lutea (CL, 29.6). However, treatment did affect the
      percentage of gilts ovulating (P<0.05) with fewer 10 AU FSH with 15% LH-treated
      gilts ovulating (15%) compared to controls (72%), whereas the other treatments
      did not differ (range, 44-65%). Experiment 2 tested whether FSH in
      polyvinlypyrrolidinone (PVP) could induce estrus and ovulation with reduced
      administration frequency. Gilts (n=105) were assigned to receive 15 AU FSH with
      10% LH in one (1P) or two sc administrations (2P) whereas controls received
      PG600. There was no treatment effect on incidence of estrus (64%) or cysts (22%).
      However, the percentage of gilts ovulating was lower for 1P (56%), but did not
      differ (P<0.05) between 2P (83%) and controls (85%). Treatment influenced
      ovulation rate (P<0.05) with 2P having more CL (24) than controls (12) and 1P
      (19). Results indicated that 10 and 15 AU FSH induced estrus and ovulation,
      although high LH content proved detrimental. Further, 15 AU FSH with 10% LH in
      PVP allowed for reduced administration frequency without compromising ovulation.

PMID- 16620940
TI  - In vitro production and transfer of cat embryos in the 21st century.
AB  - Appreciable progress has been made in the development of assisted reproductive
      technology (ART) for creating in vitro embryos in cats. Moreover, the extent of
      advancement in the last decade has been similar, albeit of more modest magnitude,
      to that seen in some other domestic and laboratory species, particularly when the
      disparities in financial, and, hence, scientific, resources are considered. The
      recent progress in domestic felid ART has made it possible to envisage their
      potential role in supporting the conservation of endangered felid species, which,
      in reality, is a multifarious process requiring wide-ranging, yet coordinated
      approaches. The prospect of incorporating ART into that intricate domain, with
      limited exceptions, remains a long-term, but highly motivating objective.
      Meanwhile, the straightforward accessibility and abundant supply of domestic cat
      gametes from local veterinary clinics provides a valuable and practical source of
      material for further research on the basic aspects of in vitro oocyte maturation,
      fertilization and early embryo development. Furthermore, extrapolating the
      domestic biotechniques to non-domestic felids has produced encouraging results in
      some species.

PMID- 16620941
TI  - Standardising bull breeding soundness evaluations and reporting in Australia.
AB  - There is substantial variation in bull breeding soundness evaluation procedures
      and reports in Australia; the situation is compounded by difficulties in
      interpretation and the validity of many reports. In an effort to overcome this,
      the scientific literature was reviewed [Fordyce G. In: Fordyce G, editor. Bull
      fertility: selection and management in Australia. Eight Mile Plains, Australia:
      Australian Cattle Vets; 2002] and the needs of stakeholders were considered in
      preparing a manual, Evaluating and Reporting Bull Fertility [Entwistle KW,
      Fordyce G. Evaluating and reporting bull fertility. Eight Mile Plains, Australia:
      Australian Cattle Vets; 2003.] that outlined standards for assessing and
      reporting bull breeding soundness. A new recording and reporting system, called
      Bull Reporter, is based on standards from this manual and groups bull fertility
      traits into five summary categories: Scrotum, Physical, Crush-side Semen, Sperm
      Morphology, and Serving. The client will generally select which categories they
      wish to have included in the evaluation to suit their specific purposes. While
      there is adequate room for comments, the veterinarian is not required to make an
      overall judgment of whether the bull has normal capacity to sire calves under
      natural mating management, but ensures the standards for each selected category
      are met. Professional, standardised, easy-to-read reports are produced either
      electronically [Entwistle KW, Fordyce G. Evaluating and reporting bull fertility.
      Eight Mile Plains, Australia: Australian Cattle Vets; 2003.] or manually. A bull
      owner or their agent signs the certificate to affirm that bulls have not
      undergone procedures to rectify faults which may have otherwise caused them to
      fail the standards. An accreditation system for assessing sperm morphology was
      established because of its demonstrated relationship with pregnancy rates and
      because of the difficulties in achieving consistent and accurate assessments
      among laboratories. It is considered that Bull Reporter is applicable to beef and
      dairy bulls across all levels of management, genotypes and environments
      throughout Australia, with substantial potential for application elsewhere in the
      world.

PMID- 16620942
TI  - Clinical management of pregnancy in cats.
AB  - Average gestation length in domestic cats is 65.6 days, with a range of 52-74
      days. Average reported litter size is 4.0 kittens per litter; litter size is not
      correlated with number of matings in a given estrus. Superfecundation is common
      in domestic cats; superfetation never has been definitively proven to occur.
      Eclampsia may occur during pregnancy in queens, with non-specific clinical signs.
      Ectopic pregnancy and uterine torsion have been reported. Pregnancy loss may be
      due to infectious causes, including bacteria, viruses or protozoa, or non
      infectious causes, such as hypoluteoidism and chromosome errors.

PMID- 16620943
TI  - Comparison of an extender containing defined milk protein fractions with a skim
      milk-based extender for storage of equine semen at 5 degrees C.
AB  - A problem of semen extenders based on milk or egg yolk is the fact that these
      biological products consist of a variety of substances. Extenders containing only
      components with clearly protective effects on spermatozoa would thus be an
      advantage. In this study, we have compared the effects of an extender containing
      defined caseinates and whey proteins only (EquiPro, defined milk protein
      extender) with skim milk extender on equine spermatozoa during cooled storage.
      The defined milk protein extender was used with and without the antioxidant N
      acetyl cysteine (NAC). In a second experiment, semen was diluted with PBS or
      defined milk protein extender and was either stored directly or 90% of seminal
      plasma was removed by centrifugation and replaced by defined milk protein
      extender before storage. In both experiments, eight stallions were available for
      semen collections. Motility, velocity and membrane integrity of spermatozoa were
      determined by CASA immediately after semen processing and after 24, 48 and 72 h
      of storage at 5 degrees C. Total motility after 24 h of storage was lowest in
      semen diluted with PBS (p<0.05 versus all extenders). At 48 and 72 h, motility of
      spermatozoa in defined milk protein extender was significantly (p<0.05) higher
      than in PBS or skim milk extender. Velocity of spermatozoa after storage was
      highest in defined milk protein extender. Membrane integrity after storage was
      significantly (p<0.05) lower in semen diluted with PBS than in semen diluted with
      both extenders. Addition of NAC was without effect on the examined parameters.
      Centrifugation further increased the percentage of motile and membrane-intact
      spermatozoa in the defined milk protein extender (p<0.05). Velocity of
      spermatozoa in this extender was not negatively affected by centrifugation.

PMID- 16620944
TI  - The role of structural prediction in rapid syntactic analysis.
AB  - A number of recent electrophysiological studies of sentence processing have shown
      that a subclass of syntactic violations elicits very rapid ERP responses,
      occurring within around 200 ms of the onset of the violation. Such findings raise
      the question of how it is possible to diagnose violations so quickly. This paper
      suggests that very rapid diagnosis of errors is possible specifically in
      situations where the diagnosis problem is tightly constrained by specific
      expectations generated before the critical word is presented. In an event-related
      potentials (ERP) study of visual sentence reading participants encountered
      violations of a word order constraint (...Max's of...) that has elicited early
      ERP responses in previous studies. Across conditions the illicit sequence was
      held constant, while sentence context was used to manipulate the expectation for
      a noun following the possessor Max's, by manipulating the possibility of ellipsis
      of the head noun. Results showed that the anterior negativity elicited by the
      word category violation was attenuated when the availability of ellipsis reduced
      the expectation for a noun in the position of the offending preposition of, with
      divergence between conditions starting around 200 ms after the onset of the
      violation. This suggests a role for structural expectations in accounting for
      very fast syntactic diagnosis processes.

PMID- 16620945
TI  - Overall Assessment of the Speaker's Experience of Stuttering (OASES): documenting
      multiple outcomes in stuttering treatment.
AB  - This paper describes a new instrument for evaluating the experience of the
      stuttering disorder from the perspective of individuals who stutter. Based on the
      World Health Organization's International Classification of Functioning,
      Disability, and Health [World Health Organization (2001). The International
      Classification of Functioning, Disability, & Health. Geneva: World Health
      Organization], the Overall Assessment of the Speaker's Experience of Stuttering
      (OASES) collects information about the totality of the stuttering disorder,
      including: (a) general perspectives about stuttering, (b) affective, behavioral,
      and cognitive reactions to stuttering, (c) functional communication difficulties,
      and (d) impact of stuttering on the speaker's quality of life. This paper
      summarizes scale development, reliability and validity assessment, and scoring
      procedures so clinicians and researchers can use the OASES to add to the
      available evidence about the outcomes of a variety of treatment approaches for
      adults who stutter. EDUCATIONAL OBJECTIVES: As a result of this activity,
      participants will be able to: (1) identify key issues related to the
      documentation of treatment outcomes in stuttering; (2) discuss the components of
      the international classification of functioning, disability, and health as they
      relate to the documentation of stuttering treatment outcomes; (3) evaluate and
      use a new measurement instrument for assessing the outcomes of stuttering
      treatment from the perspective of the person who stutters.

PMID- 16620948
TI  - The impact of hydrofluoric acid surface treatments on the performance of a
      porcelain laminate restorative material.
AB  - OBJECTIVES: Hydrofluoric (HF) acid etching increases the bond strength between
      composite resin and porcelain surfaces and has been advocated as a pre
      cementation technique for ceramic restorations. The internal surface flaw
      distribution which is implicated in the premature failure of ceramic restorations
      is modified by the etching process and little agreement exists amongst
      researchers as to the appropriate etching regime. The purpose of the current
      study was to examine the impact of HF acid concentration and etching time on the
      performance of a low fusing feldspathic porcelain. METHODS: Sets of 30 Vitadur
      Alpha dentin porcelain discs (15 mm diameter, 0.9 mm thickness) were etched with
      HF acid of three different concentrations (5, 10 and 20%) and for three different
      etching periods (45, 90 and 180s). Mean flexure strengths, standard deviations
      and the associated Weibull moduli (m) and characteristic stress (sigma(0)) were
      determined using bi-axial flexure (ball on ring). Contact profilometry was
      utilised to characterise the roughness of the etched porcelain surfaces. RESULTS:
      A univariate general linear analysis of means revealed a significant reduction in
      the mean strength values of the as-fired control compared with groups subjected
      to HF acid etching. Further significance (P<0.05) was discovered with the impact
      of acid concentration. Altering etching time also resulted in changes in the
      reliability of the fracture strength data. Contact profilometry demonstrated an
      increase in surface roughness following HF acid etching and an increase in
      roughness associated with increasing HF concentration. CONCLUSIONS: Etching of
      feldspathic porcelain is a dynamic process and the impact is dependent on
      substrate constitution, surface topography, acid concentration and etching time.
      A significant reduction of the flexural strength of a low fusing feldspathic
      porcelain has been demonstrated to result from etching and clear evidence exists
      that the nature of surface flaw modification is a function of etching time and HF
      acid concentration. Favourable combinations of HF acid concentration and etching
      time have been identified which enhance the reliability of the porcelain utilised
      although variability in clinical technique will result in the reduced reliability
      of porcelain laminate restorations in function.

PMID- 16620947
TI  - Properties and cyclic fatigue of glass infiltrated tape cast alumina cores
      produced using a water-based solvent.
AB  - OBJECTIVE: The purpose of this study was to investigate the properties of tape
      cast alumina composite produced using a water-based solvent and its possible
      clinical use as an all ceramic crown system in a fixed partial denture.
      Durability of the system will be measured by fatigue test to simulate the
      masticating conditions of the oral cavity. METHODS: The optimal weight ratio of
      water-based alumina tape was determined by tensile strength, shrinkage ratio and
      durability. The coefficient of thermal expansion, fracture toughness, biaxial
      flexural strength and flexural strength after fatigue test of a composite
      produced from alumina tape at optimal weight ratios were determined and compared
      to In-Ceram alumina core (control). RESULTS: The weight ratio of
      alumina/(alumina+binder+plasticizer) of 0.84 and binder/(binder+plasticizer) of
      0.5 was observed to be the optimal composition for achieving excellent composite
      properties. Coefficient of thermal expansion of the sintered alumina tape was
      observed to be 7.3x10(-6)/degrees C, and this value was increased to 7.5x10(
      6)/degrees C after infiltrating the sintered tape with glass. The fracture
      toughness and biaxial flexural strength of glass infiltrated alumina tape was
      observed to be 4.6 MPa m(1/2) and 498 MPa, respectively. After cyclic loading for
      10(2)-10(6) cycles, no significant change in the biaxial flexural strength was
      observed between the glass infiltrated alumina core and the In-Ceram alumina core
      (p>0.05). SIGNIFICANCE: The observed properties provide evidence that the water
      based tape cast alumina-glass composite is suitable for clinical use as an all
      ceramic crown system in a fixed partial denture.

PMID- 16620949
TI  - The effect of shot blasting and heat treatment on the fatigue behavior of
      titanium for dental implant applications.
AB  - OBJECTIVES: The effect of shot blasting treatment on the cyclic deformation and
      fracture behavior of a commercial pure titanium with two different
      microstructures; equiaxed (alpha-phase) and acicular (martensitic alpha'-phase)
      was investigated. METHODS: Fatigue tests were carried out in artificial saliva at
      37 degrees C. Cyclic deformation tests were carried out up to fracture and
      fatigue crack nucleation and propagation were analysed. Residual stresses were
      determined by means of X-ray diffraction. RESULTS: The results show that shot
      blasting treatment improves fatigue life in the different microstructures
      studied. The equiaxed phase has improved mechanical properties compared to the
      acicular one. Despite the fact that control of the variables of shot blasting is
      not precise because of the nature of the treatment, it improves the fatigue life
      by the fact that the initiation site of the fatigue crack changes from the
      surface of the specimen to the interior of the shot blasted specimen. This is a
      consequence of the layer of compressive residual stresses that the treatment
      generates on titanium surfaces. The acicular morphology of the martensite favors
      crack propagation along the interface of the alpha' plates. SIGNIFICANCE: Shot
      blasting, which is widely used on titanium dental implants in order to favour
      their osseointegration, can also improve their fatigue resistance.

PMID- 16620950
TI  - Residual monomer of reline acrylic resins. Effect of water-bath and microwave
      post-polymerization treatments.
AB  - OBJECTIVES: This study compared the residual monomer (RM) in four hard chair-side
      reline resins (Duraliner II-D, Kooliner-K, Tokuso Rebase Fast-TRF and Ufi Gel
      hard-UGH) and one heat-polymerized denture base resin (Lucitone 550-L), which was
      processed using two polymerization cycles (short-LS and long-LL). It was also
      investigated the effect of two after polymerization treatments on this RM
      content. METHODS: Specimens (n=18) of each material were produced following the
      manufacturers' instructions and then divided into three groups. Group I specimens
      were left untreated (GI-control). Specimens of group II (GII) were given post
      polymerization treatment by microwave irradiation. In group III (GIII), specimens
      were submitted to immersion in water at 55 degrees C (reline resins-10 min;
      denture base resin L-60 min). The RM was analyzed using high performance liquid
      chromatography (HPLC) and expressed as a percentage of RM. Data were analyzed by
      two-way ANOVA followed by Tukey's test (alpha=0.05). RESULTS: Comparing control
      specimens, statistical differences were found among all materials (p<0.05), and
      the results can be arranged as K (1.52%)>D (0.85%)>UGH (0.45%)>LL (0.24%)>TRF
      (0.14%)>LS (0.08%). Immersion in hot water (GIII) promoted a significant (p<0.05)
      reduction in the RM for all materials evaluated compared to control (GI), with
      the exception of LL specimens. Materials K, UGH and TRF exhibited significantly
      (p<0.05) lower values of RM after microwave irradiation (GII) than in the control
      specimens. SIGNIFICANCE: The reduction in RM promoted by water-bath and microwave
      post-polymerization treatments could improve the mechanical properties and
      biocompatibility of the relining and denture base materials.

PMID- 16620951
TI  - Preparation and characterization of sodium hexameta phosphate cross-linked
      chitosan microspheres for controlled and sustained delivery of centchroman.
AB  - The cross-linked microspheres using chitosan with different molecular weights and
      degree of deacetylation have been prepared in presence of sodium hexameta
      polyphosphate (SHMP) as physical cross-linker. The degree of cross-linking
      through electrostatic interactions in chitosan microspheres has been evaluated by
      varying the charge density on chitosan and varying degree of dissociation of
      sodium hexameta polyphosphate by solution pH. The degree of deacetylation and
      molecular weight of chitosan has controlled electrostatic interactions between
      hexameta polyphosphate anions and chitosan, which played significant role in
      swelling, loading and release characteristics of chitosan microspheres for
      centchroman. The microspheres prepared by hexameta polyphosphate anions cross
      linker were compact and more hydrophobic than covalently cross-linked
      microspheres, which has been attributed to the participation of all amino groups
      of chitosan in physical cross-linking with added hexameta polyphosphate anions.
      The microspheres prepared under different experimental conditions have shown an
      initial step of burst release, which was followed by a step of controlled release
      for centchroman. The extent of drug release in these steps has shown dependence
      on properties of chitosan and degree of cross-linking between chitosan and added
      polyanions. The degree of swelling and release characteristics of microspheres
      was also studied in presence of organic and inorganic salts, which shown
      significant effect on controlled characteristics of microspheres due to
      variations in ionic strength of the medium. The initial step of drug release has
      followed first order kinetics and become zero order after attaining an
      equilibrium degree of swelling in these microspheres. The microspheres prepared
      using chitosan with 62% (w/w) degree of deacetylation and molecular weight of
      1134kgmol(-1) have shown a sustained release for centchroman for 50h at 4% (w/w)
      degree of cross-linking with SHMP.

PMID- 16620952
TI  - Expression and purification of native and truncated forms of CadF, an outer
      membrane protein of Campylobacter.
AB  - Campylobacter is now recognized as the most common bacterial agent of
      gastroenteritis. The adhesion of bacteria to intestinal cells is a major step in
      human colonization. The binding of Campylobacter jejuni cells to fibronectin
      (Fn), a component of the extra cellular matrix, is mediated by a 37,000 outer
      membrane protein termed CadF for Campylobacter adhesion to Fn. CadF protein is
      very hard to purify from Campylobacter membranes. In order to study the
      conformation of this protein, we set out to clone, express, purify, and re-fold
      the CadF protein. The nucleotide sequence encoding the N-terminal domain of the
      CadF protein was cloned in a pET-based expression vector. The recombinant protein
      was further produced in Escherichia coli, purified from inclusion bodies, and
      refolded. More specifically, the purification experiments were set-up as follows:
      (i) protein aggregates were collected from cell-lysates, solubilized in urea and
      enriched by ion-exchange chromatography; (ii) refolding was achieved by drop-by
      drop dilution method in detergent containing buffer and monitored by CD
      measurements; (iii) the protein was finally purified to homogeneity by gel
      filtration chromatography. In spite of our success in purifying the N-terminal
      domain of the CadF protein, repeated attempts to express and purify the entire
      cadF gene in E. coli failed. Using a novel approach, we found it possible to
      express the entire cadF gene fused to a hexa-histidine encoding nucleotide
      sequence in C. jejuni. This allowed the expression, synthesis, and purification
      of the recombinant CadF-His tagged protein from C. jejuni by nickel affinity
      chromatography followed by gel filtration chromatography. In summary, we
      developed a novel strategy to produce significant quantities of a recombinant N
      terminal portion of the CadF protein (46.5 microg/mg of bacterial dry weight) and
      of the native CadF protein (3.5 microg/mg of bacterial dry weight) for further
      studies.

PMID- 16620953
TI  - Expression and purification of recombinant poly(A)-specific ribonuclease (PARN).
AB  - PARN is a poly(A)-specific ribonuclease that degrades the poly(A) tail of mRNA.
      We have established conditions for expressing soluble recombinant human PARN. We
      investigated different Escherichia coli strains, expression vectors, media and
      growth conditions. We found that PARN expressed from pET33 in BL21(DE3) grown in
      TB and induced at OD595 approximately 1 with 1 mM IPTG yielded mg amounts of
      soluble PARN per litre culture. Further, a purification protocol was established
      to purify PARN. We use His-tag affinity chromatography, HiTrap Q HP ion exchange
      chromatography and 7-Me-GTP-Sepharose affinity chromatography. This purification
      procedure render a 90-95% pure PARN. Purified recombinant PARN has enzymatic
      activity and will be used for further mechanistic and structural studies.

PMID- 16620954
TI  - Isolation, purification and characterization of silk protein sericin from cocoon
      peduncles of tropical tasar silkworm, Antheraea mylitta.
AB  - A high molecular weight water-soluble glue protein, sericin was identified in the
      cocoon peduncle (a strong thread connecting the cocoons to the branches of the
      tree with a ring) of the tropical tasar silkworm, Antheraea mylitta. The sericin
      was isolated by 8M urea containing 1% sodium dodecyl sulfate and beta
      mercaptoethenol (2%) or by 1% sodium chloride. The protein was purified by gel
      filtration chromatography. In SDS-PAGE, a single band of approximately 200kDa was
      detected both in non-reducing and reducing conditions. Amino acid analysis showed
      that the protein is enriched in glycine and serine. There is a slight difference
      observed in amino acid composition between the sericin from cocoon peduncle and
      cocoon of A. mylitta. Secondary structure estimation by circular dichroism
      spectrometry showed 36.7% beta-sheets, 52.7% random coils, 10.6% turns and no
      helices.

PMID- 16620955
TI  - Large-scale production, bacterial localization assessment and immobilized metal
      affinity chromatography purification of a human single-chain Fv antibody against
      alphaIIb-beta3 integrin.
AB  - Our objective was to investigate the Escherichia coli localization (such as
      supernatant, cytoplasm and inclusion bodies) of an anti-alphaIIb-beta3
      (alphaIIbbeta3) scFv fragment referred to as scFv[EBB3] produced in batch
      fermentation. Immobilized metal affinity chromatography (IMAC) purification was
      performed on supernatant using expanded bed absorbed technology (EBA) and on
      sonicated cells in native conditions over an immobilized copper-ion affinity
      column. Inclusion bodies were solubilized before IMAC purification and the
      refolding procedure was performed on the column. The majority of scFv[EBB3] were
      present as inclusion bodies (55%), whereas 36% were found in the cytoplasm and
      only 9% secreted in the supernatant. The scFv activity was assessed by enzyme
      linked immunosorbent assay (ELISA), flow cytometry and immunohistochemistry
      analyses performed on a thrombus induced in vivo on an atherosclerotic rabbit
      model.

PMID- 16620956
TI  - In vitro re-endothelialization of detergent decellularized heart valves under
      simulated physiological dynamic conditions.
AB  - The production of viable biological heart valves is of central interest in tissue
      engineering (TE). The aim of this study was to generate decellularized heart
      valves with an intact ultra-structure and to repopulate these with endothelial
      cells (EC) under simulated physiological conditions. Decellularization of ovine
      pulmonary valve conduits was performed under agitation in detergents followed by
      six wash cycles. Viability of EC cultures exposed to washing solution served to
      prove efficiency of washing. Resulting scaffolds were free of cells with
      preserved extracellular matrix. Biomechanical standard tension tests demonstrated
      comparable parameters to native tissue. Luminal surfaces of decellularized
      valvular grafts were seeded with ovine jugular vein EC in dynamic bioreactors.
      After rolling culture for 48 h, pulsatile medium circulation with a flow of 0.1
      L/min was started. The flow was incremented 0.3 L/min/day up to 2.0 L/min (cycle
      rate: 60 beats/min), while pH, pO2, pCO2, lactate and glucose were maintained at
      constant physiological levels. After 7 days, a monolayer of cells covered the
      inner valve surface, which expressed vWF, indicating an endothelial origin. A
      complete endothelialization of detergent decellularized scaffold can be achieved
      under simulated physiological circulation conditions using a dynamic bioreactor
      system, which allows continuous control of the culture environment.

PMID- 16620957
TI  - Combination of 3D tissue engineered scaffold and non-viral gene carrier enhance
      in vitro DNA expression of mesenchymal stem cells.
AB  - The objective of this study is to enhance the expression of a plasmid DNA for
      mesenchymal stem cells (MSC) by combination of 3-dimensional (3D) tissue
      engineered scaffolds and non-viral gene carrier. As a carrier of plasmid DNA,
      dextran-spermine cationic polysaccharide was prepared by means of reductive
      amination between oxidized dextran and the natural oligoamine, spermine. As the
      MSC scaffold, collagen sponges reinforced by incorporation of poly(glycolic acid)
      (PGA) fibers were used. A complex of the cationized dextran and plasmid DNA of
      BMP-2 was impregnated into the scaffolds. MCS were seeded into each scaffold and
      cultured by a 3D culture method. When MSC were cultured in the PGA-reinforced
      sponge, the level of BMP-2 expression was significantly enhanced by the
      cationized dextran-plasmid DNA complex impregnated into the scaffold than by the
      cationized dextran-plasmid DNA complex in 2-dimensional (2D) (tissue culture
      plate) culture method. The alkaline phosphatase activity and osteocalcin content
      of transfected MSC cultured in the PGA-reinforced sponge were significantly
      higher compared with 2D culture method. We conclude that combination of
      cationized dextran plasmid DNA complex and 3D tissue engineered scaffold was
      promising to promote the in vitro gene expression for MSC.

PMID- 16620959
TI  - Fibroblast remodeling activity at two- and three-dimensional collagen
      glycosaminoglycan interfaces.
AB  - Previously we demonstrated that high throughput gene expression experiments can
      yield novel information about how cells respond to a collagen-glycosaminoglycan
      (GAG) three-dimensional culture environment. The goal of the current study was to
      determine which of these differences result from culture in a three-dimensional
      construct versus those caused simply by the presence of the collagen-GAG
      biomaterial. To make this distinction, cells were cultured both in collagen-GAG
      scaffolds fabricated using a phase separation method and on thin two-dimensional
      coatings of the same material. Control cells were grown on standard tissue
      culture polystyrene (TCPS). Cell response was measured using histology and
      microarray analysis and select results were verified with real time polymerase
      chain reaction (RT-PCR) assays. Genes involved in matrix remodeling (matrix
      components, matrix metalloproteinases and growth factors) and angiogenesis (VEGF,
      HGF and HMOX) were shown to be differentially expressed between the treatment
      conditions. Several matrix metalloproteinases (MMPs) were up regulated in mesh
      grown cell while some of their inhibitors (TIMPs) were down regulated. These
      results suggest that the three-dimensional presentation of the collagen-GAG
      material to the cells is required to stimulate the observed increase in
      fibroblast remodeling behavior.

PMID- 16620958
TI  - Controlled release of gentamicin from calcium phosphate-poly(lactic acid-co
      glycolic acid) composite bone cement.
AB  - Modification of a self setting bone cement with biodegradable microspheres to
      achieve controlled local release of antibiotics without compromising mechanical
      properties was investigated. Different biodegradable microsphere batches were
      prepared from poly(lactic-co-glycolic acid) (PLGA) using a spray-drying technique
      to encapsulate gentamicin crobefate varying PLGA composition and drug loading.
      Microsphere properties such as surface morphology, particle size and antibiotic
      drug release profiles were characterized. Microspheres were mixed with an
      apatitic calcium phosphate bone cement to generate an antibiotic drug delivery
      system for treatment of bone defects. All batches of cement/microsphere
      composites showed an unchanged compressive strength of 60 MPa and no increase in
      setting time. Antibiotic release increased with increasing drug loading of the
      microspheres up to 30% (w/w). Drug burst of gentamicin crobefate in the
      microspheres was abolished in cement/microsphere composites yielding nearly zero
      order release profiles. Modification of calcium phosphate cements using
      biodegradable microspheres proved to be an efficient drug delivery system
      allowing a broad range of 10-30% drug loading with uncompromised mechanical
      properties.

PMID- 16620960
TI  - Nanoparticles of cationic amphiphilic cyclodextrins entangling anionic porphyrins
      as carrier-sensitizer system in photodynamic cancer therapy.
AB  - The photodynamic activity of a carrier-sensitizer system consisting of
      heterotopic colloidal nanoparticles (diameter 100-1000 nm) of a cationic
      amphiphilic cyclodextrin, heptakis(2-omega-amino-O-oligo(ethylene oxide)-6
      hexylthio)-beta-CD (SC6CDNH2) encapsulating the anionic 5,10,15,20-tetrakis(4
      sulfonatophenyl)-21H,23H-porphyrin (TPPS) is investigated by an interdisciplinary
      approach involving the combination of time-resolved absorption and emission
      techniques with in vitro studies on cultured tumor cells. In a range of
      TPPS:SC6CDNH2 molar ratios between 1:10 and 1:50 these nanoparticles preserve the
      photodynamic properties of the entrapped photoactive agent. In fact, the triplet
      state of TPPS is efficiently populated, very long-lived and, as a consequence,
      able to produce singlet oxygen (the essential species for the photodynamic
      action) with quantum yield comparable to the free TPPS. Photodynamic efficacy of
      the carrier/sensitizer system is proven by in vitro studies on tumor Hela cells
      treated with TPPS:SC6CDNH2 at different molar ratio, showing significant cells
      death upon illumination with visible light.

PMID- 16620961
TI  - Georg Schmorl on trophoblasts in the maternal circulation.
AB  - Trafficking of cells between the fetus and its mother provides indirect clues to
      the underlying pathophysiology of pregnancy. Georg Schmorl first documented the
      presence of fetal cells in the maternal body and emphasized the importance of the
      placenta in eclampsia. Although his classic paper, written in 1893, is widely
      cited today, few investigators have actually read the paper, as it was published
      in German [Schmorl G., Pathologisch-anatomische Untersuchungen uber Puerperal
      Eklampsie. Verlag FCW Vogel, Leipzig; 1893]. Our goal was to translate the paper
      into English and critically re-evaluate its conclusions from a 21st century
      perspective. Schmorl was remarkably astute in his assessment of the pathologic
      changes that were seen in the 17 women on whom he performed complete autopsies.
      He found similar severe changes in all of the women, implying a common
      pathogenesis. This was in direct contrast to the then current doctrine. He was
      the first to observe the presence of thrombi containing multinucleated syncytial
      giant cells in the lungs of the women and speculated that they were of placental
      origin. To support his hypothesis he performed animal experiments. He also
      recognized that feto-maternal trafficking occurred in normal gestations but was
      increased in pregnancies affected by eclampsia. Using sophisticated molecular
      techniques we can now precisely confirm what Schmorl so elegantly described.

PMID- 16620962
TI  - Effects of different human chorionic gonadotrophin preparations on trophoblast
      differentiation.
AB  - Recent evidence from the literature suggested that hCG preparations purified from
      urine of pregnant women, which are widely used in in vitro studies and IVF
      programs, may contain contaminants such as EGF. To determine the putative
      biological effects of the contaminating growth factor, we here investigated
      distinct trophoblast differentiation processes in the presence of various hCG
      compounds. Western blot analyses indicated that treatment of trophoblastic SGHPL
      5 cells and purified term trophoblasts with potentially EGF-contaminated hCG (hCG
      A) resulted in auto-phosphorylation of the EGF receptor at tyrosine 1173 whereas
      supplementation of another urine-purified hCG preparation (hCG-B), recombinant
      holo-hCG or recombinant alphahCG had no effects. Phosphorylation was specifically
      blocked by the EGF receptor inhibitor PD153035. Urinary hCG-A was most effective
      in promoting invasion of SGHPL-5 cells through Matrigel-coated transwells, but
      increased invasiveness was also observed in the presence of hCG-B or recombinant
      holo-hCG. Similarly, the extent of syncytialisation of term trophoblasts,
      quantitated by nuclei in desmoplakin-negative areas, was highest upon addition of
      hCG-A or recombinant EGF as a control. PD153035 reduced invasion and fusion of
      trophoblasts supplemented with hCG-A, but did not diminish the effects provoked
      by hCG-B. In conclusion, the data suggest that the EGF contamination of hCG
      considerably affects trophoblast function. Experiments using EGF-free hCG
      preparations demonstrate that the hormone increases trophoblast invasion and
      syncytialisation.

PMID- 16620963
TI  - Tyrosine kinase modulation of protein kinase C activity regulates G protein
      linked Ca2+ signaling in leukemic hematopoietic cells.
AB  - We have used a recombinant mouse pre-B cell line (TonB210.1, expressing Bcr/Abl
      under the control of an inducible promoter) and several human leukemia cell lines
      to study the effect of high tyrosine kinase activity on G protein-coupled
      receptor (GPCR) agonist-stimulated cellular Ca(2+) release and store-operated
      Ca(2+) entry (SOCE). After induction of Bcr/Abl expression, GPCR-linked SOCE
      increased. The effect was reverted in the presence of the specific Abl inhibitor
      imatinib (1microM) and the Src inhibitor PP2 (10microM). In leukemic cell lines
      constitutively expressing high tyrosine kinase activity, Ca(2+) transients were
      reduced by imatinib and/or PP2. Ca(2+) transients were enhanced by specific
      inhibitors of PKC subtypes and this effect was amplified by tyrosine kinase
      inhibition in Bcr/Abl expressing TonB210.1 and K562 cells. Under all conditions
      Ca(2+) transients were essentially blocked by the PKC activator PMA. In Bcr/Abl
      expressing (but not in native) TonB210.1 cells, tyrosine kinase inhibitors
      enhanced PKCalpha catalytic activity and PKCalpha co-immunoprecipitated with
      Bcr/Abl. Unlike native TonB210.1 cells, Bcr/Abl expressing cells showed a high
      rate of cell death if Ca(2+) influx was reduced by complexing extracellular
      Ca(2+) with BAPTA. Our data suggest that tonic inhibition of PKC represents a
      mechanism by which high tyrosine kinase activity can enhance cellular Ca(2+)
      transients and thus exert profound effects on the proliferation, apoptosis and
      chemotaxis of leukemic cells.

PMID- 16620964
TI  - Arachidonic acid is a physiological activator of the ryanodine receptor in
      pancreatic beta-cells.
AB  - Pancreatic beta-cells have ryanodine receptors but little is known about their
      physiological regulation. Previous studies have shown that arachidonic acid
      releases Ca(2+) from intracellular stores in beta-cells but the identity of the
      channels involved in the Ca(2+) release has not been elucidated. We studied the
      mechanism by which arachidonic acid induces Ca(2+) concentration changes in
      pancreatic beta-cells. Cytosolic free Ca(2+) concentration was measured in fura-2
      loaded INS-1E cells and in primary beta-cells from Wistar rats. The increase of
      cytosolic Ca(2+) concentration induced by arachidonic acid (150microM) was due to
      both Ca(2+) release from intracellular stores and influx of Ca(2+) from
      extracellular medium. 5,8,11,14-Eicosatetraynoic acid, a non-metabolizable
      analogue of arachidonic acid, mimicked the effect of arachidonic acid, indicating
      that arachidonic acid itself mediated Ca(2+) increase. The Ca(2+) release induced
      by arachidonic acid was from the endoplasmic reticulum since it was blocked by
      thapsigargin. 2-Aminoethyl diphenylborinate (50microM), which is known to inhibit
      1,4,5-inositol-triphosphate-receptors, did not block Ca(2+) release by
      arachidonic acid. However, ryanodine (100microM), a blocker of ryanodine
      receptors, abolished the effect of arachidonic acid on Ca(2+) release in both
      types of cells. These observations indicate that arachidonic acid is a
      physiological activator of ryanodine receptors in beta-cells.

PMID- 16620965
TI  - Presenilin mutations linked to familial Alzheimer's disease reduce endoplasmic
      reticulum and Golgi apparatus calcium levels.
AB  - Presenilin-1 and -2 (PS1 and PS2) mutations, the major cause of familial
      Alzheimer's disease (FAD), have been causally implicated in the pathogenesis of
      neuronal cell death through a perturbation of cellular Ca(2+) homeostasis. We
      have recently shown that, at variance with previous suggestions obtained in cells
      expressing other FAD-linked PS mutations, PS2-M239I and PS2-T122R cause a
      reduction and not an increase in cytosolic Ca(2+) rises induced by Ca(2+) release
      from stores. In this contribution we have used different cell models: human
      fibroblasts from controls and FAD patients, cell lines (SH-SY5Y, HeLa, HEK293,
      MEFs) and rat primary neurons expressing a number of PS mutations, e.g. P117L,
      M146L, L286V, and A246E in PS1 and M239I, T122R, and N141I in PS2. The effects of
      FAD-linked PS mutations on cytosolic Ca(2+) changes have been monitored either by
      using fura-2 or recombinant cytosolic aequorin as the probe. Independently of the
      cell model or the employed probe, the cytosolic Ca(2+) increases, caused by
      agonist stimulation or full store depletion by drug treatment, were reduced or
      unchanged in cells expressing the PS mutations. Using aequorins, targeted to the
      endoplasmic reticulum or the Golgi apparatus, we here show that FAD-linked PS
      mutants lower the Ca(2+) content of intracellular stores. The phenomenon was most
      prominent in cells expressing PS2 mutants, and was observed also in cells
      expressing the non-pathogenic, "loss-of-function" PS2-D366A mutation. Taken as a
      whole, our findings, while confirming the capability of presenilins to modify
      Ca(2+) homeostasis, suggest a re-evaluation of the "Ca(2+) overload" hypothesis
      in AD and a new working hypothesis is presented.

PMID- 16620966
TI  - Interferon regulatory factor-1 myelodysplasia and leukemia.

PMID- 16620967
TI  - Expression of tumor protein D52-like genes in childhood leukemia at diagnosis:
      clinical and sample considerations.
AB  - The tumor protein D52 gene or protein is frequently overexpressed in several
      carcinomas, and has been identified as a B cell differentiation marker. D52-like
      genes are also differentially expressed in particular haematological
      malignancies, where transcript or protein levels may reflect cellular
      proliferative or differentiative status. We used RT-PCR to analyse the expression
      of three D52-like genes in bone marrow at the time of ALL or AML diagnosis in
      children. Whereas D53 transcripts were undetectable in all samples, D52 and D54
      transcripts were frequently detected in ALL and AML, where they were frequently
      co-expressed. While D52 and D54 transcripts were detected in T-ALL and pre-B ALL
      at comparable frequencies, D52 was less frequently detected in ALL bone marrow
      with hyperdiploid karyotypes, compared with samples with normal karyotypes. We
      also found that total RNA yields significantly differed according to D52 and D54
      expression status, and that bone marrow freezer storage time (up to 945 days)
      differed significantly according to D52 expression status. These results indicate
      that D52-like genes are not ubiquitously expressed in leukemic bone marrow in
      children, and that RNA sample parameters may influence measures of gene
      expression more than commonly appreciated.

PMID- 16620968
TI  - PRAME is a membrane and cytoplasmic protein aberrantly expressed in chronic
      lymphocytic leukemia and mantle cell lymphoma.
AB  - The preferentially expressed antigen in melanoma (PRAME) gene is aberrantly
      expressed in chronic lymphoproliferative disorders (CLD). We produced and
      characterized an anti-PRAME monoclonal antibody (MoAb), which was then applied in
      a quantitative flow cytometric (QFC) method to evaluate PRAME expression in
      leukemic cells from the peripheral blood (PB) of 47 patients with chronic
      lymphocytic leukemia and seven with mantle cell lymphoma as well as in the PB
      mononuclear cells (PBMCs) and B lymphocytes from 15 healthy subjects.
      Approximately 90% of CLD, but none of the normal samples, presented more than 20%
      of PRAME+ lymphocytes. Moreover, the intensity of PRAME expression was
      significantly higher in CLD cells compared to normal B lymphocytes and PBMCs. By
      immunofluorescence microscopy and by permeabilized flow cytometry we demonstrated
      that PRAME is a membrane antigen and a cytoplasmic protein aberrantly expressed
      in malignant CLD. Our results suggest that the analysis of PRAME protein may
      contribute for the distinction between normal and leukemic cells in CLD, and that
      PRAME may be a potential target for therapy.

PMID- 16620969
TI  - Cryptococcus lung infection complicating fludarabine treatment in a chronic
      lymphocytic leukemia patient.

PMID- 16620970
TI  - Production of vascular endothelial growth factor in T-cell prolymphocytic
      leukemia.
AB  - We describe a 79-year-old man who had massive pleural effusion and a
      proliferation of prolymphocytic leukemia cells in the peripheral blood, bone
      marrow, and pleural effusion fluid. Immunophenotyping of leukemia cells revealed
      either CD3+CD4+CD8-CD25+ or CD3+CD4+CD8+CD25+. The antibody against human T-cell
      lymphotropic virus type I was negative. A diagnosis of T-PLL was made. The level
      of VEGF in the plasma or pleural effusion fluid was very high. Moreover,
      polymerase chain reaction analysis demonstrated an expression of VEGF mRNA in the
      leukemia cells, indicating a production of VEGF from leukemia cells and its
      involvement in the pathogenesis of T-PLL.

PMID- 16620971
TI  - Successful treatment of relapsed AML after allogeneic stem cell transplantation
      with azacitidine.
AB  - Therapeutic options for patients with relapse of MDS or high risk AML after
      allogeneic stem cell transplantation are limited. We here present the case of a
      64-year-old female patient with MDS, who received peripheral blood stem cells
      from her HLA-identical brother after a non-myeloablative conditioning regimen.
      Two months after allogeneic transplantation she suffered from a relapse, now
      fulfilling WHO criteria for AML with a bone marrow blast count of 91%. We then
      decided to treat her with azacitidine, a DNA methyltransferase inhibitor with
      proven antileukemic activity. The patient achieved a complete haematological
      response after two cycles and full donor chimerism after a single dose of donor
      lymphocytes. We postulate that azacitidine acts through a direct reduction of
      malignant cells and may in addition augment the immunologic effects of donor
      lymphocyte infusions.

PMID- 16620972
TI  - The third International Congress on Myeloproliferative and Myelodysplastic
      Syndromes.
AB  - This meeting was convened by Richard T. Silver and co-chaired by Jerry L. Spivak.
      It was held from 27 to 29 October 2005 in Washington, DC. Thirty-one invited
      speakers from seven different countries participated in the conference, which was
      attended by more than 300 individuals from 23 countries. As in previous years, a
      clinical symposium for patients, held the day before the symposium, was sponsored
      by the Cancer Research and Treatment Fund, Inc., New York, NY 10021. This meeting
      report provides a summary of the five sessions prepared and highlighted by one of
      the session chairs. In addition to the formal presentations on the biology,
      clinical aspects and management of these diverse marrow stem cell disorders,
      there was considerable interest generated because of the availability of several
      new agents that have been recently approved. A special luncheon satellite
      symposium was devoted to the dramatic changes in the therapeutic options for the
      myelodysplastic syndromes, sponsored by MGI Pharma, Inc. The keynote address was
      presented by Dr. George Q. Daley from Harvard Medical School and the Children's
      Hospital Medical Center. He reviewed the molecular steps in the formation of the
      Philadelphia chromosome and some of the newly described mutations leading to
      resistance to chemotherapy (see Section 4).

PMID- 16620973
TI  - Usefulness of JAK2V617F mutation in distinguishing idiopathic erythrocytosis from
      polycythemia vera.
AB  - Idiopathic erythrocytosis (IE) is a primary erythrocytosis not fulfilling the
      criteria for polycythemia vera (PV) diagnosis. In order to verify the
      relationship between IE and PV, we screened JAK2V617F mutation in a consecutive
      series of 11 IE and, for comparison, in 15 PV. JAK2V617F mutation was screened by
      both cDNA sequencing and mutation specific PCR in both peripheral blood and bone
      marrow samples. All 11 IE tested negative for JAK2V617F mutation, which,
      conversely, occurred in 11/15 (73.3%) PV. Our results demonstrate that JAK2V617F
      is absent in IE and may represent a useful molecular marker for distinguishing IE
      from PV.

PMID- 16620974
TI  - RNAi suppression of recognition protein mediated immune responses in the tobacco
      hornworm Manduca sexta causes increased susceptibility to the insect pathogen
      Photorhabdus.
AB  - Bacterial pathogens either hide from or overcome the immune response of their
      hosts. Here we show that two different species of insect pathogenic bacteria,
      Photorhabdus luminescens TT01 and Photorhabdus asymbiotica ATCC43949, were both
      recognized by the immune system of their host Manduca sexta, as indicated by a
      rapid increase in the levels of mRNAs encoding three different inducible
      microbial recognition proteins, Hemolin, Immulectin-2 and peptidoglycan
      recognition protein. RNA interference (RNAi)-mediated inhibition of expression
      ("knock-down") of each of these genes at the level of both mRNA and protein was
      achieved through injection of double-stranded RNA (dsRNA). Knock-down of any one
      of these genes markedly decreased the ability of the insects to withstand
      infection when exposed to either species of Photorhabdus, as measured by the rate
      at which infected insects died. RNAi against Immulectin-2 caused the greatest
      reduction in host resistance to infection. The decreased resistance to infection
      was associated with reduced hemolymph phenoloxidase activity. These results show
      not only that Photorhabdus is recognized by the Manduca sexta immune system but
      also that the insect's immune system plays an active, but ultimately ineffective,
      role in countering infection.

PMID- 16620975
TI  - The fly Drosophila subobscura: a natural case of innate immunity deficiency.
AB  - The Drosophila subobscura larvae were found to be unable to form a capsule around
      a parasitic egg or an inert foreign body. The specificity and physiological
      causes of this incapacity were also explored: analysis of the circulating
      hemocytes showed that no lamellocyte was ever found in D. subobscura host larvae.
      Therefore, the fly D. subobscura is the first discovered animal species to
      present an innate immunodeficiency against a wide range of parasites. This is
      contrary to the theories that propose that all organisms, in natural conditions,
      are potentially able to defend themselves against parasitization. This unexpected
      finding opens evolutionary debates about the cost of immune resistance not only
      at the level of a population, but also of a whole species. We believe this
      species of fruitfly could become a new model system to study genes involved in
      hematopoiesis, and in a larger context to better understand defence reactions in
      organisms.

PMID- 16620976
TI  - Comparative analysis of the plasmids from two isolates of "Candidatus Phytoplasma
      australiense".
AB  - Two plasmids from the plant-pathogenic mollicute "Candidatus Phytoplasma
      australiense" were completely sequenced from two isolates derived from different
      plant hosts. Plasmid pPAPh2 (3607bp) was obtained from Phormium showing Phormium
      yellow leaf symptoms and pPASb11 (3635bp) from strawberry showing strawberry
      lethal yellows symptoms. The plasmids varied in their copy number and nucleotide
      sequence yet contained the same four open reading frames (ORFs). The deduced
      amino acid sequence derived from ORF1 shares similarity with hypothetical
      proteins encoded on the plasmids from onion yellows and beet leafhopper
      transmitted virescence agent phytoplasmas. The deduced amino acid sequences of
      both ORF2 and ORF3 share similarity with functionally unknown proteins on the
      chromosome of onion yellows phytoplasma. An ORF with a similar sequence to ORF2
      is also present on the chromosome of "Ca. P. australiense." The deduced amino
      acid sequence derived from ORF4 is most similar to replication proteins encoded
      by other phytoplasma plasmids and by geminiviruses, the only protein on the
      plasmids for which a putative function can be assigned. The identities of the
      deduced amino acid sequences of ORF1, ORF2, ORF3, and ORF4 between pPAPh2 and
      pPASb11 were 89, 68, 91, and 68%, respectively; the differences being consistent
      with the subgroup status of the parental phytoplasmas.

PMID- 16620977
TI  - Bioaccumulation of heavy metals in Liza saliens from the Esmoriz-Paramos coastal
      lagoon, Portugal.
AB  - Heavy metal (Cu and Zn) concentrations in liver, gills, and muscle of leaping
      grey mullet, Liza saliens, from the Portuguese Esmoriz-Paramos coastal lagoon
      were measured to evaluate their bioaccumulation as a function of sediment
      contamination. The highest metal concentrations were observed in the liver (254
      mg Cu kg(-1)) and gills (114 mg Zn kg(-1)). Bioaccumulation factors (BAFs) were
      found to follow the order: Cu-liver>Cu-gills>Cu-muscle and Zn-gills>Zn-liver>Zn
      muscle. The highest BAFs were observed in the organs mainly implicated in metal
      metabolism and a significant positive relationship was found between BAFs and
      fish age. These results suggest the loss of homeostatic capacity of L. saliens
      under chronic metal exposure leading to bioaccumulation. Furthermore, Cu-liver
      and Zn-gills accumulation can be good environmental indicators of metal stress in
      L. saliens.

PMID- 16620978
TI  - Ecotoxicological evaluation of cork-boiling wastewaters.
AB  - Toxicity tests with Vibrio fischeri, Daphnia magna, and Lemna minor were used to
      evaluate acute and chronic toxicity of cork-boiling wastewaters and correlation
      analysis was performed with physicochemical parameters. Acute toxicity values
      (EC(50)) ranged from 2.3% to 24.2% in the Microtox test and from 4.4% to 29.5% in
      the Daphnia test. According to these values, 78% of the samples were classified
      as acutely toxic to the most sensitive species (V. fischeri). Significant
      correlation was obtained between EC(50) and chemical oxygen demand, biochemical
      oxygen demand after 5 days, total organic carbon, tannin and lignin and total
      solids. No significant correlation was found between the two acute tests. The D.
      magna chronic test showed significant differences between all tested
      concentrations and the control, with an EC(50) of 0.32%. An EC(50) value of 26.0%
      was calculated for L. minor. For the analysis of cork-boiling wastewater toxicity
      and routine biomonitoring, the use of the Microtox test is suggested, to afford
      greater environmental protection.

PMID- 16620979
TI  - Effectiveness of ZnCl2 in protecting against nephrotoxicity induced by HgCl2 in
      newborn rats.
AB  - This work investigated the preventive effects of ZnCl(2) on renal and hepatic
      alterations induced by HgCl(2) in young rats. Wistar rats of 3 days old were
      treated (s.c.) on consecutive days with saline or ZnCl(2) 27 mg/kg/day from the
      3rd to the 7th and with saline or HgCl(2) 5.0mg/kg/day from the 8th to the 12th
      day of life. Pups were sacrificed 24h after the last dose and samples were
      collected. The creatinine and urea dosages, used as renal parameters, presented
      increases of 35% and 500%, respectively. The alanine aminotransferase and lactic
      dehydrogenase activities, used as hepatic parameters, presented a decrease (40%)
      and no alteration, respectively, by mercury exposure. The glycemia was diminished
      and the hepatic glycogen was not modified by mercury. All the mercury effects
      were prevented by zinc. These results suggest that mercury intoxication of young
      rats alters the renal function but does not modify the hepatic parameters, and
      previous exposure to zinc is able to avoid the renal damage.

PMID- 16620980
TI  - From biomarkers to population responses in Nereis diversicolor: assessment of
      stress in estuarine ecosystems.
AB  - Suborganismal responses to toxicants can be sensitive tools to assess marine
      pollution, but their ecological significance is a matter of debate. Among these
      biomarkers, those linked to reproduction are most probably related to
      populational effects. To test this hypothesis, Nereis diversicolor were collected
      in the multipolluted Seine estuary and the comparatively clean Authie estuary
      (France). Energy reserves were higher in Authie worms, suggesting a better
      physiological status. The number of oocytes per female was higher for the
      polychaetes from the Authie, but it was related to the size of animals, which was
      higher at this site. Densities of worms were depleted in the Seine compared to
      those in Authie. Demographic structure of the Seine population was also altered.
      The concomitant changes in energy reserves, egg production, and population
      structure and density suggest that the effects on biomarkers and at the
      population level are related.

PMID- 16620981
TI  - Mutagenicity of leachates from industrial solid wastes using Salmonella reverse
      mutation assay.
AB  - Leachates derived from dry wastes of the metal, tannery, and dye industries of
      the state of Uttar Pradesh (India) were analyzed for their mutagenic potential
      using reverse mutation assay. Both the spot and plate incorporation assays were
      conducted with four tester strains of Salmonella typhimurium (TA97a, TA98, TA100,
      and TA102). The metal concentrations in the samples were also determined. The
      result suggests that leachates derived from metal and tannery wastes possess
      mutagenic properties. The findings are indicative of the type of environmental
      and health risks posed by improper waste disposal.

PMID- 16620982
TI  - Enrichment of elements in detritus from a constructed wetland and consequent
      toxicity to Hyalella azteca.
AB  - In a pilot constructed wetland treatment system specifically designed to treat
      constituents of flue gas desulfurization wastewater, detritus adsorbs
      significantly high concentrations of Hg, Se, and As. Results of this research
      indicate that Hg, Se, and As were enriched in detritus from Schoenoplectus
      californicus and Typha angustifolia collected from the constructed wetland by
      factors up to 4600, 26,300, and 15,600, respectively. As an important food source
      for many organisms, element enrichment makes the detritus an even greater source
      of contaminants to the food web. Results demonstrate that the natural
      decomposition of plants in this constructed wetland treatment system produces
      detritus enriched with Hg, Se, and As at levels potentially hazardous to aquatic
      organisms. To completely assess ecological risks associated with the use of
      constructed wetland treatment systems, contaminant enrichment, bioavailability,
      and toxicity in detritus must be considered.

PMID- 16620983
TI  - From manual gesture to speech: a gradual transition.
AB  - There are a number of reasons to suppose that language evolved from manual
      gestures. We review evidence that the transition from primarily manual to
      primarily vocal language was a gradual process, and is best understood if it is
      supposed that speech itself a gestural system rather than an acoustic system, an
      idea captured by the motor theory of speech perception and articulatory
      phonology. Studies of primate premotor cortex, and, in particular, of the so
      called "mirror system" suggest a double hand/mouth command system that may have
      evolved initially in the context of ingestion, and later formed a platform for
      combined manual and vocal communication. In humans, speech is typically
      accompanied by manual gesture, speech production itself is influenced by
      executing or observing hand movements, and manual actions also play an important
      role in the development of speech, from the babbling stage onwards. The final
      stage at which speech became relatively autonomous may have occurred late in
      hominid evolution, perhaps with a mutation of the FOXP2 gene around 100,000 years
      ago.

PMID- 16620984
TI  - Altered brain activity processing in high-anxiety rodents revealed by challenge
      paradigms and functional mapping.
AB  - Pathological anxiety involves aberrant processing of emotional information that
      is hypothesized to reflect perturbations in fear/anxiety pathways. The affected
      neurobiological substrates in patients with different anxiety disorders are just
      beginning to be revealed. Important leads for this research can be derived from
      findings obtained in psychopathologically relevant rodent models of enhanced
      anxiety, by revealing where in the brain neuronal processing in response to
      diverse challenges is different to that in animals with lower anxiety levels.
      Different functional mapping methods in various rodent models, including
      psychogenetically selected lines or genetically modified animals, have been used
      for this purpose. These studies show that the divergent anxiety-related
      behavioral response of high-anxiety- vs. normal and/or low-anxiety rodents to
      emotional challenges is associated with differential neuronal activation in
      restricted parts of proposed fear/anxiety circuitries including brain areas
      thought to be important in stress, emotion and memory. The identification of
      neuronal populations showing differential activation depends in part on the
      applied emotional challenge, indicating that specific facets of elicited fear or
      anxiety preferentially engage particular parts of the fear/anxiety circuitry.
      Hence, only the use of an array of different challenges will reveal most affected
      brain areas. A number of the neuronal substrates identified are suggested as
      candidate mediators of dysfunctional brain activation in pathological anxiety.
      Indeed, key findings revealed in these rodent models show parallels to
      observations in human symptom provocation studies comparing anxiety disorder
      patients with healthy volunteers. Work to investigate exactly which of the
      changed neuronal activation patterns in high-anxiety rodents has to be modulated
      by therapeutic drugs to achieve effective anxiolysis and via which neurochemical
      pathways this can be accomplished is at its early stages but has identified a
      small number of promising candidates. Extending these approaches should help to
      provide further insight into these mechanisms, revealing new leads for
      therapeutic targets and strategies.

PMID- 16620985
TI  - Helicobacter pylori-induced indoleamine 2,3-dioxygenase activity in vivo is
      regulated by TGFB1 and CTLA4 polymorphisms.
AB  - The chronic gastric infection caused by Helicobacter pylori is known to be
      associated with several, probably interrelated, immunomodulatory effects, such as
      protection from atopic diseases, induction of CD4+ CD25+ T regulatory (T(reg))
      cells and increase in indoleamine-pyrrole 2,3-dioxygenase (IDO) -dependent
      suppressive mechanisms. As these mechanisms, as well as the strength of the
      infection, are very probably genetically controlled, we selected candidate genes
      (TGFB1, CTLA4) known to be involved in the activation of T(reg) cells. We
      examined the association of their polymorphisms (TGFB1 C-509T, CTLA4 A+49G) with
      blood IDO activity in H. pylori seropositive individuals. Genotypes were
      determined from 391 healthy adults. H. pylori infection was verified by detecting
      H. pylori IgG antibodies in sera. Concentrations of tryptophan (trp) and
      kynurenine (kyn), the main metabolite, were determined by reverse-phase high
      performance liquid chromatography, and kyn/trp ratio was used as an indicator of
      IDO activity. The activity was higher in H. pylori seropositive individuals, but
      this increase was only detected in individuals with CTLA4+49 AA genotype or in
      carriers of TGFB1-509 allele T. This suggests that H. pylori induced IDO activity
      is regulated by TGFB1 and CTLA4, and that IDO is a mediator of the T cell
      suppressive effects of these genes.

PMID- 16620986
TI  - Gangliosides, Ab1 and Ab2 antibodies II. Light versus heavy chain: An idiotype
      anti-idiotype case study.
AB  - The antibody heavy chain is generally more important than the light chain for the
      interaction with the antigen, although many reports demonstrate the influence of
      the light chain in the antibody binding properties. The heavy chains of anti-N
      glycolyl-ganglioside P3 mAb and anti-idiotypic 1E10 mAb display complementary
      charged residues in their H-CDRs, particularly in H-CDR3. A basic residue in P3
      mAb H-CDR1 was shown to be crucial for the interaction with the antigen and 1E10
      mAb. The immunogenetic features of three other P3 mAb anti-idiotypic mAbs are now
      analyzed. One of them bears the same heavy chain as 1E10 mAb and a different
      light chain, but differs in its binding to P3 mAb mutants where H-CDR basic
      residues were replaced and in the binding to 1E10-specific phagotopes. Chimeric
      hybrid antibodies with P3 and 1E10 mAb heavy chains and unrelated light chains
      were obtained to further determine the importance of heavy chains in P3 and 1E10
      mAb binding properties. One of the P3 heavy chain hybrid antibodies retained the
      specificity of P3 mAb with slight affinity differences. The heavy chains appear
      to play the main role in these mAb interactions, with the light chains modulating
      the affinity to their ligands.

PMID- 16620987
TI  - Expression of beta-defensins pBD-1 and pBD-2 along the small intestinal tract of
      the pig: lack of upregulation in vivo upon Salmonella typhimurium infection.
AB  - Defensins are antimicrobial peptides that play an important role in the innate
      immune response in the intestine. Up to date, only one beta-defensin (pBD-1), has
      been described in pig, which was found to be expressed at low levels in the
      intestine. We set-up a quantitative PCR method to detect the gene expression of
      pBD-1 and a newly discovered porcine beta-defensin, pBD-2. Expression of pBD-1
      mRNA increased from the proximal to the distal part of the intestine whereas pBD
      2 expression decreased. The main gene expression sites for pBD-2 were kidney and
      liver, whereas pBD-1 was mainly expressed in tongue. The porcine small intestinal
      segment perfusion (SISP) technique was used to investigate effects of Salmonella
      typhimurium DT104 on intestinal morphology and pBD-1 and pBD-2 mRNA levels in
      vivo. The early responses were studied 2, 4 and 8 h post-infection in four
      separate jejunal and ileal segments. Immunohistochemistry showed invasion of the
      mucosa by Salmonella and changes in intestinal morphology. However, no
      concomitant changes in expression of either pBD-1 or pBD-2 were observed. We
      conclude that at least two defensins are differentially expressed in the
      intestine of pigs, and that expression of both defensins is not altered by S.
      typhimurium under these conditions.

PMID- 16620988
TI  - Identification and characterization of suppressor of cytokine signaling 3 (SOCS
      3) homologues in teleost fish.
AB  - The suppressor of cytokine signaling 3 (SOCS-3) is a member of a newly discovered
      protein family, which have been shown to regulate the responses of many immune
      cytokines, such as interferon (IFN), interleukin-2 (IL-2) and IL-6, etc., by
      inhibiting Janus kinase (JAK)-signal transducers and activators of transcription
      (STAT) signaling in a negative auto-regulatory manner. Although SOCS-3 was well
      characterized in several mammal species, there was still no report in fish. In
      present study, we initially identified and characterized the SOCS-3 genes from
      three fishes, the Tetraodon nigroviridis, the Danio rerio and the Fugu rubripes.
      The results showed that Tetraodon SOCS-3 gene located within a 2666 bp genomic
      fragment of chromosome 3, transcribed into a 1445 bp mRNA including 273 bp 5' UTR
      (untranslated region), 606 bp ORF (open reading frame) and 566 bp 3' UTR.
      Tetraodon SOCS-3 with 201aa (amino acid) has a calculated molecular mass of 22.76
      kDa and a theoretical pI of 8.99. Danio SOCS-3 gene located within a 3617 bp
      genomic fragment of chromosome 3, transcribed into a 1927 bp mRNA including 178
      bp 5' UTR, 624 bp ORF and 1125 bp 3' UTR. Danio SOCS-3 with 207aa has a
      calculated molecular mass of 23.68 kDa and a theoretical pI of 9.19. Fugu SOCS-3
      gene located within a 2842 bp genomic fragment of Scaffold_1118, transcribed into
      a 1528 bp mRNA including 209 bp 5' UTR, 606 bp ORF and 713 bp 3' UTR. Fugu SOCS-3
      with 201aa has a calculated molecular mass of 22.76 kDa and a theoretical pI of
      8.18. The fish SOCS-3-encoding genes with the same organization as the mammalians
      consist of two exons and a single intron that lies in the 5' UTR of the
      transcript. The deduced amino acid sequences of the fish SOCS-3s showed: 60.7
      61.7% sequence identity to mammalian SOCS-3s; 62.3-63.2% sequence identity to
      bird SOCS-3s; and 55.3-57.8% sequence identity to amphibian SOCS-3s. Phylogenetic
      analysis separates the fish SOCS-3s into an exclusive group. Expression study of
      Tetraodon SOCS-3 mRNA in ten selected tissues showed that it was constitutively
      expressed and induced by lipopolysaccharide (LPS) strikingly. These results
      indicated that SOCS-3s in fish may be involved in inflammatory responses. This is
      the first report of cloning and characterization of SOCS-3 cDNAs and genes in
      fish.

PMID- 16620989
TI  - The use of magnetic resonance imaging (MRI) in the study of manganese
      neurotoxicity.
AB  - Manganese (Mn), an element found in many foods, is an important and essential
      nutrient for proper health and maintenance. It is toxic in high doses, however,
      and exposure to excessive levels can result in the onset of a neurological
      disorder similar to, but distinct from, Parkinson's disease. Historically, Mn
      neurotoxicity was most commonly associated with various occupations, such as Mn
      mining, welding and steel production. More recently, increases in both blood and
      brain Mn levels have been observed in persons with liver disease or those
      receiving prolonged parenteral nutrition. Additionally, rodent data suggest that
      iron deficiency and anemia may be risk factors for Mn neurotoxicity. Clinically,
      brain Mn accumulation can be monitored in vivo using non-invasive magnetic
      resonance imaging (MRI) due to the paramagnetic nature of this element. Indeed,
      MRI has been used in a variety of settings to evaluate the brain Mn deposition in
      various populations. This review focuses on the use of MRI technology in studies
      related specifically to Mn neurotoxicity. Thus, we will examine reports using MRI
      to confirm brain Mn accumulation in human populations, and conclude with data
      from non-human primate and rodent models of Mn neurotoxicity.

PMID- 16620990
TI  - Using self-report measures in neurobehavioural toxicology: can they be trusted?
AB  - Questionnaires are one of the most common methodologies used in research on
      neurobehavioural effects in occupational and environmental health, most commonly
      for gathering information on demographic characteristics, psychological or
      neurological symptoms, mood state, or exposure to hazards. Questionnaires are
      self-report measures, so by definition are subjective, although their degree of
      subjectivity depends on the phenomenon they are measuring. For some phenomena
      questionnaires are used because they are convenient but the information can be
      obtained from other sources. For other phenomena questionnaire or self-report is
      the only way of obtaining the information, for example, feelings and experiences,
      mood or emotions. Questionnaires are essential tools in psychological and
      neurobehavioural research as they can tap into aspects of nervous system function
      that cannot be readily measured in other ways. Despite the obvious need for self
      report measures, there are a number of serious issues that threaten their
      validity as effective indicators of neurobehavioural function. This paper
      considers the implications of some of the major problems with self-report
      measures, focusing particularly on current approaches to measurement of symptoms
      and mood. It includes issues relating to validity of measures such as demand
      characteristics, malingering and under or over reporting, individual differences
      and problems of language and question style. It also includes issues relating to
      the interpretation of self-report measures, the relationship between self-report
      and performance measures, whether they reflect primary or secondary effects and
      whether they can be used as diagnostic criteria for neurobehavioural functional
      effects of occupational or environmental exposure. The paper looks at some of the
      current approaches to overcoming these problems including using interviews and
      observational methods and improving psychometric qualities of these measures.
      Self-report measures are important tools in our arsenal of measures of the
      neurobehavioural effects of occupational and environmental exposure, but they
      need to be used with care.

PMID- 16620991
TI  - Amphetamine exposure is elevated in Parkinson's disease.
AB  - BACKGROUND: Since the 1930's, amphetamine drugs have been used therapeutically
      and recreationally. High doses are associated with acute injury to axon terminals
      of dopaminergic neurons. It is unknown whether low dose exposure to amphetamine
      over a prolonged time period is associated with the development of Parkinson's
      disease (PD). METHODS: A telephone survey of drug and chemical exposure was
      administered to patients from three faculty practice clinics at UCSF. Patients
      were asked to participate if they had been diagnosed with peripheral neuropathy
      (PN), amyotrophic lateral sclerosis (ALS), or PD between the ages of 40 and 64.
      Spouses or caregivers were also asked to participate. "Amphetamine exposure" was
      defined as a prior use of amphetamine, methamphetamine or dextroamphetamine.
      "Prolonged exposure" was defined as amphetamine use that occurred more than twice
      a week for > or =3 months or weekly usage for > or =1 year and had to occur
      before diagnosis of the neurological condition. RESULTS: Prolonged exposure to
      either prescribed or non-prescribed amphetamine was common, occurring in 15% with
      PN (11/76), 13% with ALS (9/72), and 11% with PD (17/158). Prolonged amphetamine
      exposure was more frequent in diseased patients compared to spouses when all
      diseases were combined (adjusted OR=3.15, 95% CI 1.42-7.00, p=0.005). When tested
      alone, only the Parkinson's disease group retained statistical significance
      (adjusted OR=8.04, 95% CI 1.56-41.4, p=0.013). For most individuals, exposure
      occurred long before diagnosis (averages: PN 25 years, ALS 28 years, and PD 27
      years). CONCLUSIONS: The elevated rate of prolonged amphetamine exposure in PD is
      intriguing and bears further investigation.

PMID- 16620992
TI  - Individual subject sensitivity to extremely low frequency magnetic field.
AB  - It is becoming important to specify the smallest effects of extremely low
      frequency (ELF) magnetic fields (MF) on human physiology. One difficulty is that
      some people seem more sensitive and more responsive than others to MF exposure.
      Consequently, within- and between-subject differences have to be taken into
      account when evaluating these effects. As shown in previous work, human postural
      tremor is sensitive to MF exposure. But data about individual responses have not
      been examined in detail. Thus, postural tremor of 24 subjects was evaluated under
      ELF MF "on" and "off" conditions in a double-blind real/sham exposure protocol.
      The direction of the tremor changes was analyzed individually for three tremor
      characteristics. Results showed that subjects with high amplitude tremor seem to
      be more responsive to MF exposure. MF had an instantaneous effect (between "on"
      and "off" conditions) and also a more delayed and persistent one (between real
      and sham conditions), but differences were small. Moreover, due to the within-
      and between-subject variability, no statistical analysis could be done. However,
      these results do not show any potentially harmful effect of domestic or
      industrial 50 Hz MF on humans. They provide a starting point to orient future
      studies and should be taken into account in the establishment of new exposure
      limits.

PMID- 16620993
TI  - Alterations of visual evoked potentials in preschool Inuit children exposed to
      methylmercury and polychlorinated biphenyls from a marine diet.
AB  - The aim of the present study was to assess the impact of chronic exposure to
      polychlorinated biphenyls (PCBs) and methylmercury on visual brain processing in
      Inuit children from Nunavik (Northern Quebec, Canada). Concentrations of total
      mercury in blood and PCB 153 in plasma had been measured at birth and they were
      again measured at the time of testing in 102 preschool aged children.
      Relationships between contaminants and pattern-reversal visual evoked potentials
      (VEPs) were assessed by multivariate regression analyses, taking into account
      several potential confounding variables. The possible protective effects of
      selenium and omega-3 polyunsaturated fatty acids against methylmercury and PCB
      toxicity were also investigated. Results indicate that exposure to methylmercury
      and PCBs resulting from fish and sea mammal consumption were associated with
      alterations of VEP responses, especially for the latency of the N75 and of the
      P100 components. In contrast, the concomitant intake of omega-3 polyunsaturated
      fatty acids was associated with a shorter latency of the P100. However, no
      significant interactions between nutrients and contaminants were found,
      contradicting the notion that these nutrients could afford protection against
      environmental neurotoxicants. Interestingly, significant associations were found
      with concentrations of neurotoxicants in blood samples collected at the time of
      testing, i.e. at the preschool age. Our findings suggest that VEP can be used as
      a valuable tool to assess the developmental neurotoxicity of environmental
      contaminants in fish-eating populations.

PMID- 16620994
TI  - Evaluation of reliability of traditional and computerized neurobehavioral tests.
AB  - Most Korean blue-collar workers are taking government-mandated medical screening
      periodically. The periodic neurobehavioral test provides a great chance to
      evaluate the functional change of the central nervous system. To utilize periodic
      neurobehavioral tests effectively, the reliability of currently used
      neurobehavioral tests needs to be evaluated. Test-retest of neurobehavioral tests
      were conducted to evaluate the reliability of neurobehavioral tests that are
      commonly used for Korean workers. The test-retest of five computerized tests,
      simple reaction time, additions, symbol digit, digit span, and finger tapping
      speed, and five traditional tests, Benton visual retention, digit symbol, digit
      span, pursuit aiming, and pegboard, were administered to 85 college students and
      35 hospital workers over a 1 month interval. Computerized additions was found to
      have the highest test-retest reliability coefficient (r=0.90), followed by finger
      tapping speed (nondominant hand, r=0.89; dominant hand, r=0.85), symbol digit
      (r=0.82), and digit span (r=0.74). However, only two traditional tests, digit
      symbol (r=0.86) and pursuit aiming (r=0.72), showed a reliability coefficient
      greater than 0.70. These results suggest that the computerized additions, symbol
      digit, finger tapping speed, and traditional digit symbol are more satisfactory
      for periodical evaluation of the central nervous system of workers exposed to
      neurotoxic substances in Korea.

PMID- 16620995
TI  - Adapting the medaka embryo assay to a high-throughput approach for developmental
      toxicity testing.
AB  - Chemical exposure during embryonic development may cause persistent effects, yet
      developmental toxicity data exist for very few chemicals. Current testing
      procedures are time consuming and costly, underlining the need for rapid and low
      cost screening strategies. While in vitro methods are useful for screening, these
      methods do not replicate all the intricacies of embryonic development and should
      ideally be complemented by an in vivo screening strategy. In this study, we
      modify a medaka fish embryo assay to meet the requirements of high-throughput,
      developmental toxicant testing in vivo. The Japanese medaka (Oryzias latipes)
      offers several advantages over traditional mammalian model systems, including
      economic husbandry, high fecundity, and rapid ex utero development. In most
      studies where fish eggs are exposed to a chemical, the exposure takes place in a
      common vessel, with many embryos being exposed to the same solution. This type of
      design is not amenable to high-throughput methodology, does not allow the
      investigator to follow the same embryo throughout gestation, and may confound
      statistical analysis of the results. Therefore, we developed a 96-well microtiter
      plate method to facilitate exposure of individual medaka embryos in single wells
      and compared this approach to the common vessel method using the industrial
      solvent dimethyl sulfoxide (DMSO) as the test compound. At lower DMSO
      concentrations (0% or 1%), the 96-well microtiter plate assay replicated results
      obtained using the common vessel exposure method. There was, however, increased
      lethality and decreased hatching rate in the bottle-reared embryos treated with
      the higher DMSO concentrations (5% or 10%). Because the embryos reared in the 96
      well microtiter plates never showed increased adverse effects (as compared to the
      bottle-reared embryos) at any DMSO concentration, we conclude that the 96-well
      microtiter plate assay provides a rapid and efficient alternative for
      developmental toxicity screens that utilize fish embryos.

PMID- 16620996
TI  - Organochlorine pesticide exposure in essential tremor: a case-control study using
      biological and occupational exposure assessments.
AB  - Essential tremor (ET) is a common neurological disorder. Its etiology and
      pathogenesis are not well understood and several environmental factors (i.e.,
      toxicants) have been studied. Organochlorine pesticides (OCPs) are potent tremor
      producing chemicals. These pervasive environmental contaminants have been linked
      with other tremor disorders (e.g., Parkinson's disease) but they have not been
      assessed in ET cases. Our objective was to test the hypothesis that ET is
      associated with OCP exposure. Serum OCP concentrations and lifetime occupational
      histories were assessed in ET cases and control subjects. Six serum OCP
      concentrations (p,p'-DDE, p,p'-DDT, beta-hexachlorocyclo-hexane, oxychlordane,
      trans-nonachlor, and dieldrin) were assessed. Data from a lifetime occupational
      history were reviewed by a blinded industrial hygienist. The six serum OCP
      concentrations were similar in 136 ET cases and 144 control subjects. There was
      no association in ET cases between the six serum OCP concentrations and total
      tremor score. Three (2.2%) ET cases versus 9 (6.3%) controls had past
      occupational exposure to OCPs (OR=0.34, 95% CI=0.09-1.28, p=0.10). Although OCPs
      have been associated with other tremor disorders, we were not able to find an
      association between the six most tremorogenic OCPs and ET. Our data suggest that
      these tremor-producing chemicals are not of major etiological importance in our
      patients with ET.

PMID- 16620997
TI  - Arsenic-induced gene expression changes in the neural tube of folate transport
      defective mouse embryos.
AB  - Arsenic injected intraperitoneally (i.p.) during early organogenesis to small
      pregnant laboratory rodents (mouse, rat, and hamster) induces several congenital
      defects in the progeny. Among those abnormalities consistently and predominantly
      observed are exencephaly and encephalocele. These severe defects of the central
      nervous system originate from a corrupted process of neurulation and are better
      known as neural tube defects (NTDs). In order to understand the mechanism of
      arsenate-induced NTDs, we designed studies in which highly sensitive Folr2
      nullizygous mice were injected intraperitoneally with sodium arsenate at the
      beginning of the neural tube formation process. This specific knockout mouse and
      the arsenic exposure conditions were chosen as they were known to provide a high
      incidence of exencephaly in exposed embryos. We have applied gene expression
      technology to the anterior neural tube. This allowed us to study arsenic-induced
      changes in patterns of gene expression that may contribute to the development of
      neural tube defects in these mice. Using extensive data analysis approaches
      including hierarchical clustering and gene ontology analysis, we identified
      several candidate genes as well as important ontology groups that may be
      responsible for arsenic's teratogenicity. Changes in the expression of several
      genes in response to arsenic treatment in our model had previously been
      demonstrated by other investigators to also induce NTDs in murine model systems.
      These include: engrailed 1 (En-1), platelet derived growth factor receptor alpha
      (Pdgfralpha) and ephrinA7 (EphA7). We also found several gene ontology groups
      that could be implicated in arsenic's underlying teratogenicity: morphogenesis,
      oxidative phosporylation, redox response, and regulation of I-kappaB kinase/NF
      kappaB cascade. Additionally, we revealed new target genes which may be
      responsible for arsenic disrupted oxidative phosphorylation.

PMID- 16620998
TI  - The changing epidemiology of hospitalized pediatric patients in three measles
      outbreaks.
AB  - OBJECTIVES: To assess the demographic and clinical findings of measles patients
      during three epidemics from 1989 to 2001. METHODS: A total 520 medical records of
      measles patients were analyzed retrospectively and divided into three groups;
      those who were admitted during 1989-1990 (group I, 116 patients), those admitted
      during 1993-1994 (group II, 127 patients), and those admitted during 2000-2001
      (group III, 277 patients). RESULTS: For the age distribution, there was no
      difference in the proportion of < 2 years of age (61%, 58% and 57%, respectively)
      for the three groups. However, in each outbreak, there were significant
      differences in the distribution of > or = 2 years children who had mostly
      received one-dose measles-mumps-rubella (MMR) vaccination. The age distribution
      had changed with a significant increase in older children in subsequent
      outbreaks. In the last 2000-2001 outbreak, there was a pattern for increased
      attack rates with increasing interval since the initial vaccination. There was no
      statistical difference between the three groups in gender ratio, MMR vaccination
      rate in > or = 2 years of age, duration of fever, and complications. No
      difference was found in all the clinical and laboratory parameters between the
      anti-measles IgM antibody negative patients and the positive patients.
      CONCLUSIONS: The age distribution of admitted children with measles in each
      outbreak has changed over time since the introduction of one-dose MMR
      vaccination. This finding suggests that the secondary vaccine failure may have
      played a large role in the last measles outbreak.

PMID- 16620999
TI  - A case of empyema caused by Edwardsiella tarda.
AB  - In December 2003, a 57-year-old-man was diagnosed as having a hepatic tumor for
      which he had a hepatectomy. On pathology, the hepatic tumor biopsy specimen was
      diagnosed as malignant lymphoma. In February 2005, the patient was referred to
      our hospital because of fever and chest pain. A right pleural effusion was seen
      on chest X-ray. Microscopic examination of the stained pleural fluid revealed
      many neutrophils and Gram-negative rods, and Edwardsiella tarda was cultured from
      the pleural effusion fluid. These findings were consistent with an empyema caused
      by E. tarda. Therefore, we treated the patient with panipenem/betamipron and
      thoracic drainage. In this paper, we describe this rare case of empyema caused by
      E. tarda infection.

PMID- 16621000
TI  - Pseudomonas aeruginosa bacteraemia in cancer patients.

PMID- 16621001
TI  - A pseudo tumoral sinusitis caused by Bipolaris sp.
AB  - This is the first published French case of a rhinosinusitis caused by Bipolaris
      sp. in an immunocompetent patient and suggests that this organism must be
      considered as an opportunistic human pathogen in warm and damp climate like the
      south-east of France. Bipolaris sp. is the most isolated fungi in allergic fungal
      sinusitis.

PMID- 16621002
TI  - A method for quantifying directional strength and motor control of the trunk.
AB  - We describe a new apparatus for studying trunk motor control. Quasi-isometric
      trunk forces are exerted in any horizontal direction while seated, with or
      without the pelvis stabilised. Trunk force magnitude and direction are measured
      using a novel transducing system. In addition, reaction forces between the
      buttocks and the seat and between each foot and the ground are measured with
      three force plates. Twenty-four healthy subjects exerted maximal forces in eight
      directions, with and without pelvis fixation. Accuracy of trunk force
      measurements was assessed by comparing them with reaction force measurements. The
      agreement analysis showed a small mean bias of the new system of -3.0 N for force
      magnitude and 0.72 degrees for force direction. The trunk force measurement
      system was sensitive enough to detect effects of movement direction and pelvis
      fixation on maximum force magnitude. When subjects repeated the test at a later
      date there were no significant differences between the two sessions. In
      conclusion, the new device allows measurement of static and dynamic aspects of
      voluntary trunk activation in multiple directions while seated and provides
      reproducible measurements for application to longitudinal studies. The method
      should prove useful for quantifying deficits and recovery of trunk motor control
      following neurological damage.

PMID- 16621003
TI  - Classification of EMG signals using wavelet neural network.
AB  - An accurate and computationally efficient means of classifying electromyographic
      (EMG) signal patterns has been the subject of considerable research effort in
      recent years. Quantitative analysis of EMG signals provides an important source
      of information for the diagnosis of neuromuscular disorders. Following the recent
      development of computer-aided EMG equipment, different methodologies in the time
      domain and frequency domain have been followed for quantitative analysis. In this
      study, feedforward error backpropagation artificial neural networks (FEBANN) and
      wavelet neural networks (WNN) based classifiers were developed and compared in
      relation to their accuracy in classification of EMG signals. In these methods, we
      used an autoregressive (AR) model of EMG signals as an input to classification
      system. A total of 1200 MUPs obtained from 7 normal subjects, 7 subjects
      suffering from myopathy and 13 subjects suffering from neurogenic disease were
      analyzed. The success rate for the WNN technique was 90.7% and for the FEBANN
      technique 88%. The comparisons between the developed classifiers were primarily
      based on a number of scalar performance measures pertaining to the
      classification. The WNN-based classifier outperformed the FEBANN counterpart. The
      proposed WNN classification may support expert decisions and add weight to EMG
      differential diagnosis.

PMID- 16621004
TI  - Cross-chest median nerve transfer: a new model for the evaluation of nerve
      regeneration across a 40 mm gap in the rat.
AB  - A new animal model for the study of nerve regeneration in rats across a 40 mm gap
      between both median nerves is described. For autologous grafting, the ulnar
      nerves were dissected and sutured together. From the left median nerve, they were
      transplanted across the chest to the right median nerve. Animals having undergone
      this operation were observed for 12 months and periodically assessed using the
      grasping test and measurements of body-weight. For histological analysis rats
      were sacrificed after this period and axon counts were determined at the suture
      points of operated animals and in the median nerve of non-operated animals.
      Functional recovery could be seen, although partially, beginning as early as the
      fifth postoperative month, as demonstrated by the grasping test. Quantification
      of the number of axons demonstrated axonal regeneration across all three
      coaptation points. This model provides a new approach for analysis of long
      distance peripheral nerve regeneration without impairment of behaviour.

PMID- 16621005
TI  - Spatial and temporal changes of upper trapezius muscle fiber conduction velocity
      are not predicted by surface EMG spectral analysis during a dynamic upper limb
      task.
AB  - The purpose of the study was to examine the temporal and spatial correlation
      between estimates of trapezius muscle fiber conduction velocity (CV) and surface
      EMG instantaneous mean power spectral frequency (iMPF) during dynamic movement of
      the upper limb. Surface EMG signals were detected from the upper division of the
      trapezius muscle in 13 healthy volunteers using linear arrays of eight electrodes
      at three locations in the cephalad-caudal direction. Subjects were asked to tap
      with their hands in a cyclic manner between targets positioned mid thigh and 120
      degrees of shoulder flexion, to the beat of a metronome set at 88 beats per
      minute for 5 min. Muscle fiber CV and iMPF were estimated for each cycle at the
      time instant corresponding to 90 degrees of shoulder flexion. Non-significant
      correlations were identified between CV and iMPF initial values (R(2)=0.03-0.01),
      rate of change over time (R(2)=0.10-0.004) and normalized rate of change
      (R(2)=0.12-0.01) at all three locations on the upper trapezius muscle. These
      results demonstrate that both spatial and temporal variations in trapezius muscle
      fiber CV are not predicted by EMG spectral analysis during dynamic movement of
      the upper limb. This finding suggests that spectral analysis cannot be used to
      infer changes in the spatial and temporal behavior of muscle fiber CV during
      dynamic tasks.

PMID- 16621006
TI  - A novel electrode design for chronic recording of electromyographic activity.
AB  - We describe a simple, self-retaining electromyography (EMG) electrode for use in
      chronic recording of EMG activity. The EMG electrode is helical in shape,
      resembling the screw-in fixation device on many cardiac pacing electrodes. Screw
      like placement of the electrode secures it in the musculature without sutures. We
      have been using this electrode design to obtain months of quality diaphragmatic
      EMG recording in conscious rabbits. By changing the electrode wire size and coil
      dimensions, this design could be applied to chronic EMG recording in a variety of
      muscles and species.

PMID- 16621007
TI  - Cortical anastomotic veins occlusion in the rat including the assessment of
      cerebral swelling.
AB  - A rat model composed of the sacrifice of the anterior and posterior cortical
      anastomotic veins by microsurgical techniques was used for the assessment of
      brain swelling. Twenty male, 15-week-old Sprague-Dawley rats were used in this
      animal experiment. Small burr-holes were made over the anterior (the intersection
      of the line drawn from the posterior border of the orbital rim and the line drawn
      along the para-midline to the superior sagittal suture) and posterior (inferior
      point of the posterior end of the zygomatic arch) anastomotic veins. After
      performing a final inspection and describing the venous vessels, they were
      sacrificed using bipolar coagulation technique and micro-scissors. Specimens were
      evaluated using histopathological approach, albumin immunostaining technique and
      a stereological method. Hemispheric swelling, midline shift, brain oedema,
      subcortical petechial haemorrhagia, ischemia and necrosis were histopathological
      findings observed in this experimental study. The albumin immunostaining study
      demonstrated disrupted areas of the blood-brain barrier in the operated
      hemisphere. Stereological volumetric analysis revealed an 8% brain swelling in
      the operated hemispheres compared with unoperated ones. Our results suggest that
      the sacrifice of the anterior and posterior anastomotic veins may be used as an
      experimental rat model in the evaluation of brain damage and swelling caused by
      the occlusion of the venous anastomotic outflow.

PMID- 16621008
TI  - High efficiency transfection of glioma cell lines and primary cells for
      overexpression and RNAi experiments.
AB  - In order to investigate the impact of signalling proteins on the phenotype and
      malignant behavior of glioblastoma cells, we optimized the transfection procedure
      of human glioblastoma cell lines U251, U373, GaMG and of primary cells obtained
      from a patient's tumor using nucleofection technology in conjunction with plasmid
      pmaxGFP. We describe the optimization procedure, show that a high percentage of
      the cells can be transfected and that nucleofection does not cause phenotypic
      alterations of the cells. Therefore, we conclude that nucleofection is a highly
      efficient tool to deliver plasmids for transient protein overexpression and siRNA
      for specific protein knock-down to different glioblastoma cell lines or primary
      cells.

PMID- 16621009
TI  - Hippocampal (CA1) activities in Wistar rats from different vendors. Fundamental
      differences in acute ischemia.
AB  - Two-vessel occlusion, a frequently used model of global cerebral ischemia in
      rats, results in a dysfunction predominantly within the CA1 field of the
      hippocampus; it induces many processes with different time-scales. However, the
      great divergence in the results of the studies reported in the literature
      suggests valuable differences in response to hypoperfusion-induced ischemia among
      the laboratory rats used in these studies. In the present work, the acute effects
      of two-carotid occlusion-induced global ischemia (2VO) on the CA3 stimulation
      evoked population spike activity in the CA1 region of Wistar rats from different
      suppliers (Charles-River and Harlan) were compared. In the acute
      electrophysiological experiments, the hippocampal CA1 responses revealed that the
      Charles-River rats immediately compensated the 2VO much better than did the
      Harlan rats. However, 3 days later, no difference could be observed between the
      CA1 activities of these rats. The presented data show that the Wistar rats from
      different vendors represent an important source of variability in the results of
      acute experiments on the hippocampal ischemia. These observations draw attention
      to the importance of the careful choice of the laboratory rats (both strains and
      breeds) used in such experiments.

PMID- 16621010
TI  - MPScope: a versatile software suite for multiphoton microscopy.
AB  - MPScope is a software suite to control and analyze data from custom-built
      multiphoton laser scanning fluorescence microscopes. The acquisition program
      MPScan acquires, displays and stores movies, linescans, image stacks or arbitrary
      regions from up to four imaging channels and up to two analog inputs, while
      plotting the intensity of regions of interest in real-time. Bidirectional
      linescans allow 256 x 256 pixel frames to be acquired at up to 10 fps with
      typical galvanometric scanners. A fast stack mode combines movie acquisition with
      continuous z-focus motion and adjustment of laser intensity for constant image
      brightness. Fast stacks can be automated by custom programs running in an
      integrated scripting environment, allowing a 1 mm(3) cortical volume to be
      sampled in 1 billion voxels in approximately 1 h. The analysis program MPView
      allows viewing of stored frames, projections, automatic detection of cells and
      plotting of their average intensity across frames, direct frame transfer to
      Matlab, AVI movie creation and file export to ImageJ. The combination of
      optimized code, multithreading and COM (Common Object Model) technologies enables
      MPScope to fully take advantage of custom-built two-photon microscopes and to
      simplify their realization.

PMID- 16621011
TI  - Application of microdialysis to evaluate the efflux transport of estradiol 17
      beta glucuronide across the rat blood-retinal barrier.
AB  - The purpose of the present study was to evaluate vitreous humor/retina-to-blood
      efflux transport in rats and determine the efflux transport of estradiol 17-beta
      glucuronide (E17betaG) across the blood-retinal barrier (BRB) by the use of
      microdialysis. [(3)H]E17betaG and [(14)C]D-mannitol, which were used as a model
      compound for amphipathic organic anions and a bulk flow marker, respectively,
      were injected into the vitreous humor of rat eye, and a microdialysis probe was
      placed in the vitreous humor. [(3)H]E17betaG and [(14)C]D-mannitol were bi
      exponentially eliminated from the vitreous humor after vitreous bolus injection.
      The elimination rate constant of [(3)H]E17betaG during the terminal phase was 1.9
      fold greater than that of [(14)C]D-mannitol and reduced the level of [(14)C]D
      mannitol in the retinal presence of 0.3 mM E17betaG, suggesting that
      [(3)H]E17betaG is transported via a carrier-mediated efflux transport process
      across the BRB. The efflux transport of [(3)H]E17betaG was significantly
      inhibited by organic anions, such as probenecid, sulfobromophthalein, digoxin,
      and dehydroepiandrosterone sulfate, whereas it was not inhibited by p
      aminohippuric acid. In conclusion, the efflux transport of [(3)H]E17betaG across
      the rat BRB was evaluated by microdialysis and its inhibition by organic anions
      suggests organic anion transporting polypeptide 1a4-mediated E17betaG efflux
      transport at the BRB.

PMID- 16621012
TI  - Histotypic mouse parietal cortex cultures: excitation/inhibition ratio and
      ultrastructural analysis.
AB  - Primary cultures of mouse parietal cortex, prepared between postnatal day 3 (P3)
      and P9, were studied using transmission electron microscopy and HPLC of
      excitatory (aspartate and glutamate) and inhibitory neurotransmitters (glycine,
      GABA and taurine) to determine their morphological and functional development.
      Relations between excitation and inhibition (E/I) were contrasted with
      ultrastructural features over the time course of in vitro development. After 6
      days in vitro, cultured parietal cortex neurons prepared from mice at P3 had
      immature morphological characteristics, whereas P5 cultures showed a more
      developed histological structure but still with scarce synapses. The acquirement
      of histotypic characteristics was seen in P7 cultures, which contained numerous
      symmetric and asymmetric synaptic contacts. On P9, the cultures showed signs of
      tissue damage. In terms of neurotransmitter levels and E/I ratios, P7 cultures
      had relatively low E/I ratio as compared with the rest of the cultures prepared
      before or after P7. These results demonstrated that the development of inhibitory
      synaptic transmission, as indicated in the fall of E/I ratio, marked the
      maturation of cerebral cortical tissue and that the critical period to obtain
      histotypic cultures of mouse parietal cerebral cortex coincides between P5 and
      P7. This work provides useful information regarding the balance between
      excitation and inhibition as an indicative parameter for in vitro nerve cell
      survival, differentiation and maturation and reinforces the great value of
      histotypic cultures in the study of central nervous system development.

PMID- 16621013
TI  - Methods for the diagnosis of creatine deficiency syndromes: a comparative study.
AB  - The increasing number of patients with creatine deficiency syndromes (CDS)
      stresses the need to develop screening procedures for the identification these
      inherited disorders. Guanidinoacetate (GAA) and creatine (Cr) are reliable
      biochemical markers of CDS and several analytical methods to measure both
      metabolites have been developed. High-pressure liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) is quick and sensitive but, unlike HPLC and gas
      chromatography-mass spectrometry (GC/MS), it is unavailable in most laboratories.
      Thus, we decided to evaluate comparatively HPLC-MS/MS, GC/MS and HPLC methods, as
      well as to establish reference values in a healthy paediatric population.
      According to our results, these three methods may be suitable for analysing GAA
      in urine. Furthermore, Passing-Bablock plots showed good agreement among all
      three. However, when comparing the Cr/Crn ratio, our results revealed that while
      HPLC-MS/MS data were in agreement with those of GC/MS, a constant and
      proportional error was observed when compared with those of HPLC. Consequently,
      the Cr/Crn ratio obtained by the last method should be evaluated with caution.
      Our reference values for GAA and Cr/Crn ratio in urine negatively correlate with
      age. Concerning GAA and Cr measurements in plasma, it is interesting to note that
      in contrast to what was occurring in urine, GAA concentration increased
      significantly with age, while we did not find any significant difference for Cr
      values within the same age group.

PMID- 16621014
TI  - Microwave-assisted antigen retrieval and incubation with cox-2 antibody of
      archival paraffin-embedded human oligodendroglioma and astrocytomas.
AB  - Immunohistochemistry is an important tool that is often used for the diagnosis of
      pathologies; however, the length of time required to process the tissue is
      relatively long. Furthermore, the quality and sensitivity of immunohistochemical
      staining is affected by formalin fixation which results in variable loss of
      antigenicity, known as masking effect. Here we assess the effect of microwave
      irradiation on the incubation time required to obtain high quality
      immunohistochemical staining for cox-2 using archival formalin-fixed, paraffin
      embedded human oligodendrogliomas and astrocytomas. The results show that
      intermittent microwave irradiation during the incubation with the primary
      antibody reduced the time requirement to 5 min while the staining quality was
      indistinguishable from 1 or 24 h long incubations. Thus, the use of this
      procedure results in a significant saving of time which is important for a timely
      diagnosis of pathological conditions that await treatment.

PMID- 16621015
TI  - Characterizations of Hirudo medicinalis DNA promoters for targeted gene
      expression.
AB  - The expression of exogenous genes in neurons and other cells has become a
      powerful means for studying the function of encoded proteins. We report here on
      the isolation and functional analysis of three Hirudo medicinalis actin gene
      promoters and the 5' UTR of a leech elongation factor-1alpha (HmEF-1alpha) gene.
      In situ hybridization labeling revealed that the EF-1alpha gene and one of the
      actins had pan-neuronal expression, whereas, the other two actin genes were
      expressed by the embryo's body wall musculature. Comparative analysis shows that
      they all display many features typical of actin and EF-1alpha promoters from
      other species, including canonical TATA box sequences and predicted general
      transcription factor binding sites (such as CCATT, CarB boxes and CG-rich
      regions). The ability of these 5' UTR sequences to drive expression of the
      enhanced green fluorescent protein (EGFP), leech cytoplasmic actin and leech
      synaptobrevin was examined. Direct intracellular nuclear, but not cytoplasmic,
      microinjection of each of the promoter sequences was found to produce reliably
      cellular expression of the reporter construct in both neuronal and muscle cells.
      These results introduce reliable and effective methods to selectively express
      genes in individual cells of the leech in vivo during embryonic development.

PMID- 16621016
TI  - A simple modification of the water maze test to enhance daily detection of
      spatial memory in rats and mice.
AB  - The water maze is one of the most frequently used tools in behavioral
      neuroscience. Many variations of the water maze task have been used; however,
      established water maze protocols have several disadvantages. Notably, these
      protocols demand considerable time to perform reference and probe tests
      separately. Here, we suggest a modified protocol, which is rapidly performed, is
      sensitive to cognitive deficits, and can assay reference as well as strategy
      switching ability. The platform is relocated randomly within the target quadrant
      with each training trial. Because the rodents must spend more time searching
      within the target quadrant, every trial effectively becomes a probe trial. The
      rodents are then run in the switching strategy test, where the platform is
      randomly placed along the wall of the pool. The best new strategy would thus be
      to search along the walls of the pool systematically. The percent distance
      traveled and time spent near the wall is evaluated across trials, as is the
      distance traveled and time spent in the previously correct quadrant. In this way
      one can assess whether the rodent is continuing to search in the older platform
      location (i.e., displaying a strategy-switching problem) or whether it has
      successfully adopted a new search strategy.

PMID- 16621017
TI  - An examination of the Runs Test, Reverse Arrangements Test, and modified Reverse
      Arrangements Test for assessing surface EMG signal stationarity.
AB  - The purpose of this study was to examine the accuracy of the Runs Test, Reverse
      Arrangements Test, and modified Reverse Arrangements Test for assessing
      stationarity of surface electromyographic (EMG) signals. Five stationary signals
      were generated by custom programs written with LabVIEW programming software.
      These signals consisted of sine waves, sums of sine waves, and sums of sine waves
      and random noise. The sixth signal was a stationary computer generated surface
      EMG signal downloaded from the surface EMG for the non-invasive assessment of
      muscles (SENIAM) project database. There were no changes in the amplitude or
      frequency contents of the stationary signals over time. Several nonstationary
      signals were also created, including a nonstationary chirp signal generated with
      LabVIEW programming software, a nonstationary computer generated surface EMG
      signal downloaded from the SENIAM project database, and a real surface EMG signal
      recorded from the biceps brachii during a concentric isokinetic muscle action of
      the forearm flexors at a velocity of 30 degrees s(-1). Both the stationary and
      nonstationary signals were tested for stationarity using the Runs Test, Reverse
      Arrangements Test, and modified Reverse Arrangements Test. The results indicated
      that each of the three stationarity tests demonstrated at least one form of
      inaccuracy (i.e. false positive and/or false negative results) in examining the
      stationarity of the test signals. These findings may reflect the fact that these
      tests were designed to determine whether or not a signal is random, rather than
      examine signal stationarity exclusively. Thus, the Runs Test, Reverse
      Arrangements Test, and modified Reverse Arrangements Test may not be appropriate
      for assessing stationarity in surface EMG signals.

PMID- 16621019
TI  - The influence of different management systems and age on intestinal morphology,
      immune cell numbers and mucin production from goblet cells in post-weaning pigs.
AB  - At time of weaning, the immune system in piglets is not fully mature resulting in
      reduced growth and increased mortality. Early-weaned pigs transported to a
      segregated early weaning (SEW) facility have enhanced performance and gut
      development compared to conventional (CONV) pigs which may be due, in part, to
      decreased pathogen challenge. To gain further insight into SEW enhanced
      performance and gut development, gut samples from pigs weaned at 19+/-2 days were
      assessed during the post-weaning (PW) period. The numbers of cells expressing
      CD2, CD4, CD8, and CD172 (the 74-22-15 (SWC3) antibody is now known to be
      specific for CD172), MHC class II, and CD25 were quantified using
      immunohistochemistry. Additionally, samples of duodenum, jejunum, and ileum were
      evaluated for the production of neutral, acidic, and sulfuric mucins from goblet
      cells and morphological measurements were also made. No effects due to the
      management systems alone were observed for any of the parameters. However, there
      were interactive effects of age/time post-weaning and management system on the
      immune cells as well as on the mucin secreting goblet cells. There were no
      differences in gut morphology between SEW and CONV reared pigs.

PMID- 16621018
TI  - A recombinant pseudorabies virus encoding the HA gene from H3N2 subtype swine
      influenza virus protects mice from virulent challenge.
AB  - The hemagglutinin (HA) gene of A/Swine/Inner Mogolian/547/2001 (H3N2) swine
      influenza virus (SIV) was recombined into the genome of pseudorabies virus (PRV)
      Bartha-K61 vaccine strain, generating a recombinant PRV expressing the HA gene,
      designated as rPRV-HA. One group of 15 mice was inoculated intranasally (i.n.)
      with 10(5.0) PFU of rPRV-HA, and another two control groups of mice (15 mice per
      group) were mock-inoculated or inoculated with Bartha-K61. Mice inoculated with
      rPRV-HA developed hemagglutination inhibition antibodies 3 weeks post
      inoculation. Twenty-eight days post-inoculation, all mice were challenged i.n.
      with 10(5.0) TCID50 of A/Swine/Heilongjiang/74/2000 (H3N2). No challenge virus
      was isolated from vaccinated mice, and mild pathological lesions were observed
      only in lungs following challenge. The results demonstrate that the recombinant
      rPRV-HA expressing the HA gene from H3N2 SIV can protect mice from heterologous
      virulent challenge, and may represent a candidate vaccine against SIV.

PMID- 16621020
TI  - The immune response and maternal antibody interference to a heterologous H1N1
      swine influenza virus infection following vaccination.
AB  - This study investigated the efficacy of a bivalent swine influenza virus (SIV)
      vaccine in piglets challenged with a heterologous H1N1 SIV isolate. The ability
      of maternally derived antibodies (MDA) to provide protection against a
      heterologous challenge and the impact MDA have on vaccine efficacy were also
      evaluated. Forty-eight MDA(+) pigs and 48 MDA(-) pigs were assigned to 8
      different groups. Vaccinated pigs received two doses of a bivalent SIV vaccine at
      3 and 5 weeks of age. The infected pigs were challenged at 7 weeks of age with an
      H1N1 SIV strain heterologous to the H1N1 vaccine strain. Clinical signs, rectal
      temperature, macroscopic and microscopic lesions, virus excretion, serum and
      local antibody responses, and influenza-specific T-cell responses were measured.
      The bivalent SIV vaccine induced a high serum hemagglutination-inhibition (HI)
      antibody titer against the vaccine virus, but antibodies cross-reacted at a lower
      level to the challenge virus. This study determined that low serum HI antibodies
      to a challenge virus induced by vaccination with a heterologous virus provided
      protection demonstrated by clinical protection and reduced pneumonia and viral
      excretion. The vaccine was able to prime the local SIV-specific antibody response
      in the lower respiratory tract as well as inducing a systemic SIV-specific memory
      T-cell response. MDA alone were capable of suppressing fever subsequent to
      infection, but other parameters showed reduced protection against infection
      compared to vaccination. The presence of MDA at vaccination negatively impacted
      vaccine efficacy as fever and clinical signs were prolonged, and unexpectedly,
      SIV-induced pneumonia was increased compared to pigs vaccinated in the absence of
      MDA. MDA also suppressed the serum antibody response and the induction of SIV
      specific memory T-cells following vaccination. The results of this study question
      the effectiveness of the current practice of generating increased MDA levels
      through sow vaccination in protecting piglets against disease.

PMID- 16621021
TI  - Isotype patterns of immunoglobulins: hallmarks for clinical status and tissue
      parasite density in Brazilian dogs naturally infected by Leishmania (Leishmania)
      chagasi.
AB  - The role of anti-leishmanial immune response underlying the
      susceptibility/resistance during canine visceral leishmaniasis (CVL) has been
      recognized throughout ex vivo and in vitro investigations. Recently, we
      demonstrated that immunoglobulin levels (Igs), as well as the parasite load are
      relevant hallmarks of distinct clinical status of CVL. To further characterize
      and upgrade the background on this issue, herein, we have evaluated, in
      Leishmania (Leishmania) chagasi naturally infected dogs, the relationship between
      tissue parasitism (skin, bone marrow, spleen, liver and lymph node), the CVL
      clinical status (asymptomatic (AD), with no suggestive signs of the disease;
      oligosymptomatic (OD), with maximum three clinical signs-opaque bristles;
      localized alopecia and moderate loss of weight; symptomatic (SD), serologically
      positive with severe clinical signs of visceral leishmaniasis), and the humoral
      immunological profile of anti-Leishmania immunoglobulins (IgG, IgG1, IgG2, IgM,
      IgA and IgE). Our major statistically significant findings revealed distinct
      patterns of tissue parasite density within L. chagasi-infected dogs despite their
      clinical status, pointing out the spleen and skin as the most relevant sites of
      high parasitism during ongoing CVL. Parasite density of bone marrow and spleen
      were the most reliable parasitological markers to decode the clinical status of
      CVL. Moreover, the parasite density of bone marrow better correlates with most
      anti-Leishmania Igs reactivity. Additionally, a prognostic hallmark for canine
      visceral leishmaniasis was found, highlighting strong correlation between IgG1
      and asymptomatic disease, but with IgA, IgE and IgG2 displaying better
      association with symptomatic disease. The new aspects of this study highlighted
      pioneer findings that correlated the degree of tissue parasite density (low (LP),
      medium (MP) and high (HP) parasitism) with distinct patterns of anti-Leishmania
      Igs reactivity. In this scope, our data re-enforce the anti-Leishmania IgG but
      with IgA reactivity as the better marker for overall tissue parasitism. The
      association between clinical status, Ig profile and the tissue parasitism support
      a novel investigation on the impact of humoral immune response and
      susceptibility/resistance mechanism during ongoing CVL.

PMID- 16621022
TI  - Differential expression of genes encoding CD30L and P-selectin in cattle with
      Johne's disease: progress toward a diagnostic gene expression signature.
AB  - Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis),
      the causative agent of paratuberculosis (paraTB) or Johne's disease in ruminants,
      is a health problem for the global cattle industry with significant economic
      losses related to decreased milk production and reduced fertility. Commonly
      paraTB in cattle is diagnosed by antibody detection by serum enzyme-linked
      immunosorbent assay (ELISA), by detection of the pathogen by cultivation of
      individual faecal samples, or by in vitro measurement of cell mediated immune
      responses using the IFN-gamma test. There is an ongoing need for developing new
      diagnostic approaches as all currently available diagnostic tests for paraTB may
      fail to detect sub-clinical infection. We used cDNA microarrays to simultaneously
      measure expression of over 1300 host genes to help identify a subset of gene
      expression changes that might provide a unique gene expression signature for
      paraTB infection. In the present study, non-stimulated leukocytes isolated from
      10 sub-clinical paraTB infected cows were examined for genes being expressed at
      significantly different levels than in similar cells from control cows with the
      same herd background. We included cattle (Holstein) from two locations (Denmark
      and USA) for the microarray experiment. Our results indicate that expression
      profiles of at least 52 genes are different in leukocytes from M.
      paratuberculosis infected cattle compared to control cattle. Gene expression
      differences were verified by quantitative real-time reverse transcriptase
      polymerase chain reactions (qRT-PCR) on the same group of cattle (Holstein) used
      for the microarray experiment. In order to assess the generality of the observed
      gene expression, a second and different group of cattle (Jersey) was also
      examined using qRT-PCR. Out of the seven genes selected for qRT-PCR, CD30 ligand
      (CD30L) and P-selectin were consistently differentially expressed in freshly
      isolated leukocytes from paraTB infected and control animals of both breeds of
      cattle. Although further work is clearly needed to develop a more complete gene
      expression signature specific for paraTB, our results demonstrate that a subset
      of genes in leukocytes are consistently expressed at different levels, depending
      upon M. paratuberculosis infection status.

PMID- 16621023
TI  - Antibody and IFN-gamma responses induced by a recombinant canarypox vaccine and
      challenge infection with equine influenza virus.
AB  - In horses, equine influenza virus (EIV) is a leading cause of respiratory
      disease. Conventional inactivated vaccines induce a short-lived immune response.
      By comparison, natural infection confers a long-term immunity to re-infection. An
      aim of new equine influenza vaccines is to more closely mimic natural infection
      in order to achieve a better quality of immunity. A new live recombinant vaccine
      derived from the canarypox virus vector and expressing haemagglutinin genes of
      EIV (subtype H3N8) has been developed. Stimulation of the immune system was
      studied after immunisation with this canarypox-based vaccine and challenge
      infection by exposure to a nebulised aerosol of EIV. The humoral immune response
      was evaluated by measuring serum antibody levels using the single radial
      haemolysis (SRH) assay. The cellular immune response was assessed by the
      measurement of interferon gamma (IFN-gamma) synthesis in peripheral blood
      mononuclear cells (PBMC). Clinical signs of the disease (temperature, coughing,
      nasal discharge, dyspnoea, depression and anorexia) and virus excretion were
      monitored after challenge infection. Clinical signs and virus shedding were
      significantly reduced in vaccinates compared with unvaccinated controls. EIV
      specific immunity was stimulated by vaccination with a recombinant vaccine as
      serological responses were detected after immunisation. This study also provided
      the first evidence for increased IFN-gamma protein synthesis in vaccinated ponies
      following challenge infection with EIV compared with control ponies.

PMID- 16621024
TI  - Foals are interferon gamma-deficient at birth.
AB  - The increased vulnerability of foals to specific pathogens such as Rhodococcus
      equi is believed to reflect an innate immunodeficiency, the nature of which
      remains poorly understood. Previous studies have demonstrated that neonates of
      many species fail to mount potent Th1 responses. The current research
      investigates the ability of circulating and pulmonary lymphocytes of developing
      foals to produce interferon gamma (IFNgamma). Peripheral blood mononuclear cells
      (PBMC) were prepared from up to 10 horse foals at regular intervals throughout
      the first 6 months of life. Bronchoalveolar lavage (BAL) samples were collected
      at 1, 3 or 6 months of age from three groups of five foals. The PBMC and BAL
      cells were stimulated in vitro and IFNgamma production was measured by
      intracellular staining. In addition, RNA was extracted from freshly isolated and
      in vitro stimulated PBMC and BAL cells for quantitation of IFNgamma gene
      expression by real time PCR. Newborn foals exhibited a marked inability to
      express the IFNgamma gene and produce IFNgamma protein. This deficiency was
      observed in both circulating and pulmonary lymphocytes. However, IFNgamma gene
      expression and protein production increased steadily throughout the first 6
      months of life, reaching adult levels within the first year of life. These
      findings suggest that foals are born with an inherent inability to mount a Th1
      based cell mediated immune response which may contribute to their susceptibility
      to intracellular pathogens.

PMID- 16621025
TI  - Induction of interleukin-8 expression in porcine peripheral blood mononuclear
      cells by trans10-cis12 conjugated linoleic acid.
AB  - The chemotaxis of porcine peripheral blood polymorphonuclear cells (PMN) was
      enhanced by culture supernatant from peripheral blood mononuclear cells (PBMC)
      treated with trans10-cis12 (10t-12c) conjugated linoleic acid (CLA) or by porcine
      recombinant (pr) interleukin (IL)-8. To identify this chemotactic inducing
      factor, the culture supernatant from 10t-12c CLA treated PBMC was partially
      purified by gel filtration. Only fraction 9 contained enhanced PMN chemotactic
      activity. The chemotactic activity of fraction 9 was inhibited by an anti-prIL-8
      polyclonal antibody (pAb). Porcine IL-8 mRNA expression analyzed by a reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay was increased in PBMC by
      the addition of 10t-12c CLA. This study strongly suggests that the
      immunoenhancing effect of CLA on the chemotactic response of porcine PMN is
      mediated through IL-8 produced by CLA treated PBMC.

PMID- 16621026
TI  - Expression of tumor necrosis factor-alpha in IgM+ B-cells from bovine leukemia
      virus-infected lymphocytotic sheep.
AB  - Tumor necrosis factor (TNF)-alpha is thought to be one of the cytokines that
      account for bovine leukemia virus (BLV)-induced B-cell lymphoproliferative
      disorder, however, information on TNF-alpha expression in B-cells is limited. In
      this study, the expression of TNF-alpha in IgM(+) B-cells from BLV-infected sheep
      with or without lymphocytosis was determined. Freshly isolated IgM(+) B-cells
      from three sheep with lymphocytosis constitutively transcribed TNF-alpha mRNA.
      Although TNF-alpha mRNA expression in IgM(+) B-cells was transiently up-regulated
      after cell culture, TNF-alpha mRNA expression was markedly higher in
      lymphocytotic sheep when compared to that of non-lymphocytotic sheep or
      uninfected sheep. Expression of membrane-bound TNF-alpha on IgM(+) B-cells was
      also augmented in lymphocytotic sheep. TNF-alpha expression in lymphocytotic
      sheep may support the proliferation of B-cells.

PMID- 16621027
TI  - Pulmonary dendritic cells isolated from neonatal and adult ovine lung tissue.
AB  - Lung dendritic cells (DCs) are potent antigen presenting cells (APCs) that
      initiate and modulate the adaptive immune response upon microbial infection
      within the pulmonary environment. For the first time, neonatal and adult lung DCs
      in a large animal model were compared in these studies. Here, we isolated and
      identified lung DCs in both neonatal and adult sheep, a valuable experimental
      animal utilized in pulmonary studies of naturally occurring respiratory diseases.
      Neonatal lung DCs exhibited characteristic dendrites and morphology when observed
      by transmission electron microscopy and expressed low to moderate DEC-205,
      CD80/86, MHC class II and CD 14. Regardless of age, lung DCs were functionally
      able to endocytose FITC conjugated ovalbumin but to a lesser degree than monocyte
      derived DCs. In addition, neonatal lung DCs were demonstrated to be potent
      stimulators of allogeneic T cell proliferation. Together, these results
      demonstrate that neonatal and adult lung DCs are functionally similar. It is
      apparent from the data presented that neonatal pulmonary DCs do not exhibit an
      intrinsic functional defect that would impair their ability to take up antigen
      and stimulate naive T cells. These data support growing evidence that neonatal
      immune responses may differ from adults due to different microenvironmental
      influences rather than differences in dendritic cell maturation states.

PMID- 16621028
TI  - Bovine alveolar macrophage neurokinin-1 and response to substance P.
AB  - In this study bovine alveolar macrophage neurokinin-1 (NK-1) and the in vitro
      response to substance P (SP) exposure were investigated. Bovine alveolar
      macrophage membrane extracts separated by sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) and immunoblotted using anti-NK-1 antiserum
      demonstrated the presence of an approximately 60kDa band. Phagocytosis of
      fluorescent bioparticles by SP-exposed macrophages was 39% greater than that of
      non-exposed macrophages (P=0.0089). Likewise, there was 28% greater TNF
      production by macrophages following SP exposure compared to non-exposed controls
      (P=0.116). These results suggest that bovine alveolar macrophages respond to SP
      at least in part by enhancing phagocytosis and TNF production.

PMID- 16621029
TI  - Natural feline coronavirus infection: differences in cytokine patterns in
      association with the outcome of infection.
AB  - Natural and experimental feline coronavirus (FCoV) infection leads to systemic
      viral spread via monocyte-associated viraemia and induces systemic proliferation
      of monocytes/macrophages. In the majority of naturally infected animals, FCoV
      infection remains subclinical and is associated with generalised B and T cell
      hyperplasia, but no other pathological findings. A minority of cats, however,
      develop feline infectious peritonitis (FIP), a fatal systemic granulomatous
      disease. This is generally accompanied by B and T cell depletion. The obvious
      functional differences of lymphatic tissues in FCoV-infected cats with and
      without FIP suggest that they contribute to the outcome of FCoV infection. This
      study attempted to evaluate the functional changes in haemolymphatic tissues
      after natural FCoV infection, with special emphasis on the magnitude, phenotype
      and function of the monocyte/macrophage population. The spleen, mesenteric lymph
      nodes and bone marrow from naturally FCoV-infected cats with and without FIP and
      specific pathogen-free (SPF) control cats were examined for the quantity and
      activation state of monocytes/macrophages both by immunohistology and by
      quantitative real time PCR for the transcription of interleukin (IL)-1beta, IL-6,
      IL-10, IL-12 p40, tumour necrosis factor (TNF), granulocyte colony stimulating
      factor (G-CSF), macrophage-CSF (M-CSF) and GM-CSF. Compared to cats with FIP,
      FCoV-infected cats without FIP exhibited significantly higher IL-10 levels in the
      spleen and significantly lower levels of IL-6, G- and M-CSF in mesenteric lymph
      nodes. In cats with FIP, however, IL-12 p40 levels were significantly lower in
      lymphatic tissues in comparison to both SPF cats and FCoV-infected cats without
      FIP. In comparison to SPF cats, FIP cats had significantly higher IL-1beta levels
      and lower TNF levels in mesenteric lymph nodes and lower M-CSF levels in the
      spleen. Findings indicate that FCoV-infected cats which do not develop FIP are
      able to mount an effective FCoV-specific immune response and can avoid excessive
      macrophage activation and FIP, possibly by upregulation of IL-10 production.
      Development of FIP, however, might be due to a lack of IL-12 which inhibits an
      effective cellular immune response and allows for monocyte/macrophage activation
      and the development of FIP.

PMID- 16621030
TI  - Cloning and radiation hybrid mapping of bovine toll-like receptor-4 (TLR-4)
      signaling molecules.
AB  - Toll-like receptor (TLR)-4 is a transmembrane receptor for lipopolysaccharide, a
      highly pro-inflammatory component of the outer membrane of Gram-negative
      bacteria. To date, molecules of the TLR-4 signaling pathway have not been well
      characterized in cattle. The goal of this study was to clone and sequence the
      full-length coding regions of bovine genes involved in TLR-4 signaling including
      CASP8, IRAK1, LY96 (MD-2), TICAM2, TIRAP, TOLLIP and TRAF 6 and to position these
      genes, as well as MyD88 and TICAM1, on the bovine genome using radiation hybrid
      mapping. Results of this work indicate differences with a previously published
      bovine sequence for LY96 and a predicted sequence in the GenBank database for
      TIRAP based on the most recent assembly of the bovine genome. In addition,
      discrepancies between actual and predicted chromosomal map positions based on the
      Btau_2.0 genome assembly release were identified, although map positions were
      consistent with predicted locations based on the current bovine-human comparative
      map. Alignment of the bovine amino acid sequences with human and murine sequences
      showed a broad range in conservation, from 52 to 93%. Overall, this work should
      assist in the assembly and annotation of the bovine genome sequence, the
      identification of variations in genes critically involved in host innate
      immunity, and facilitate the study of TLR-4 signaling pathways in cattle.

PMID- 16621031
TI  - B7-1-HSA (CD80-CD24), a recombinant hybrid costimulatory molecule retains ligand
      binding and costimulatory functions.
AB  - Optimal activation of naive T lymphocyte requires two signals; an antigen
      specific signal initiated by engagement of TCR with the antigen-MHC complex and a
      costimulatory signal independent of the antigen receptor complex. Without the
      costimulatory signal, T cells become anergic. Various adhesion molecules, such as
      B7-1 (CD80) and heat stable antigen (HSA, CD24), expressed on antigen presenting
      cells have been demonstrated to provide costimulatory signals to T cells. It was
      reported that the combinations of different adhesion molecules could induce even
      stronger immune response. In this study, we made a hybrid costimulatory molecule,
      B7-1-HSA, and tested its T cell stimulatory function. Chinese hamster ovary (CHO)
      cells expressing this hybrid molecule bound both anti-CD80 and anti-CD24
      monoclonal antibodies, and induced stronger T cell proliferation than CHO cells
      expressing B7-1 or HSA alone. These results suggest that the B7-1-HSA hybrid
      molecule can deliver two costimulatory signals simultaneously that can synergize
      in inducing T cell proliferation. The purified B7-1-HSA protein reacted with both
      anti-B7-1 and anti-HSA mAbs in Western blotting and specifically mediated
      adhesion of Jurkat cells. Furthermore, purified B7-1-HSA molecule spontaneously
      incorporated onto cell membrane through its glycolipid anchor suggesting that
      this hybrid costimulatory molecule can be used in protein transfer to develop
      effective cancer vaccines.

PMID- 16621032
TI  - Of mice and men: different functions of the murine and human 2B4 (CD244) receptor
      on NK cells.
AB  - 2B4 was initially discovered on murine NK cells and T cells displaying non-MHC
      dependent cytotoxicity. Human 2B4 was cloned based on sequence homology with
      mouse 2B4. Recent evidence suggests that the function of this receptor might be
      different in the two species. Human 2B4 activates NK cell cytotoxicity and
      interferon gamma production when engaged by CD48, its ligand, on target cells.
      This activating function of human 2B4 requires recruitment of the SH2 domain
      containing molecule, SLAM-associated protein or SAP. In the absence of SAP in
      human NK cells, as occurs in immature NK cells or NK cells from X-linked
      lymphoproliferative disorder (XLPD) patients, human 2B4 acts as an inhibitory
      receptor. In contrast, in vitro and in vivo studies using 2B4-deficient mice
      suggest that the major function of mouse 2B4 is to inhibit murine NK cell
      functions when triggered by CD48 on target cells, although there are reports of
      activating function of murine 2B4. This inhibitory function of murine 2B4 is
      mediated by EAT-2, ERT and possibly other phosphatases like SHP-1 and SHIP. 2B4
      SAP interaction in mouse NK cells might be a low affinity one and might not be
      physiologically relevant considering the inhibitory function of 2B4. This
      suggests that mouse and human 2B4 diverged functionally with the evolution of
      greater affinity between 2B4 and SAP in the human species. We speculate that
      evolutionary pressure from viral infections, possibly EBV, might have led to the
      emergence of this association and activating function of 2B4 in humans.

PMID- 16621033
TI  - Antibody-mediated neuronal apoptosis: therapeutic implications for prion
      diseases.
AB  - Neuronal cell death is considered to be a hallmark in prion diseases. These
      disorders are believed to result from the post-translational conversion of a
      normal cell membrane sialoglycoprotein PrPC, composed primarily of alpha-helical
      structure, into a disease specific isoform, PrPSc that is rich in beta-sheet and
      partially proteinase-resistant. Recent in vivo studies indicate that prion
      replication can be inhibited by anti-PrP monoclonal antibodies that led to the
      indefinite delay in the development of prion disease. The recent report by
      Solforosi and colleagues has increased the need to understand pathway(s) leading
      to prion-associated apoptosis and neuronal death thought to be the cause of death
      in transmissible spongiform encephalopathy (TSE) individuals. Furthermore, these
      reports increased momentum about the use of antibody-based therapy in prion
      diseases, although great caution should be exerted when using anti-prion
      antibodies directly into the central nervous system (CNS) with special emphasis
      on refined strategies such as specific targeting of regions of the prion protein
      thought not to be involved in signalling pathways.

PMID- 16621034
TI  - Influence of extensive functional endoscopic sinus surgery (FESS) on facial
      growth in children with cystic fibrosis. Comparison of 10 cephalometric
      parameters of the midface for three study groups.
AB  - OBJECTIVES: To determine the impact of FESS after the first and before the second
      growth spurt on facial growth and in particular of the maxilla. DESIGN:
      Prospective study of 23 patients with cystic fibrosis, 13 patients requiring
      extensive endoscopic spheno-ethmoidectomy (FESS) because of massive nasal
      polyposis, with a follow-up of at least 10 years. SETTING: A cystic fibrosis
      referral centre in an academic tertiary pediatric hospital. PATIENTS: At the time
      the standard cephalometric measurements were performed all patients were adults
      with cystic fibrosis. One group of patients underwent FESS during facial growth
      (N=9), a second group of patients had no previous surgery (N=9), and in a third
      group FESS has been performed after the second growth spurt (N=5). RESULTS: No
      statistically significant differences (Kruskall-Wallis test) were found in the
      cephalometric measurements of these three patient groups. CONCLUSIONS: Extensive
      FESS after the first and before the second growth spurt has no impact on the
      outcome of facial growth.

PMID- 16621035
TI  - Bilateral epistaxis in children: efficacy of bilateral septal cauterization with
      silver nitrate.
AB  - OBJECTIVE: To evaluate the rate of control of epistaxis in patients with
      bilateral complaints using silver nitrate and to assess short-term complications
      from this therapy. STUDY DESIGN AND SETTING: Retrospective chart review with
      prospective incident case identification in a tertiary referral pediatric
      otolaryngology practice. SUBJECTS AND INTERVENTIONS: Forty-six consecutive
      patients presenting to a single pediatric otolaryngologist with complaints of
      bilateral epistaxis received bilateral silver nitrate cauterization to the
      anterior septum and were seen in follow-up 2 months later to assess for control
      of epistaxis and complications from this therapy. RESULTS: Ninety-three percent
      (43/46) of patients followed-up at 2 months after therapy. About 93% (40/43) had
      total or near-total resolution of their epistaxis. Five percent (2/43) of
      patients returned to the clinic after initial successful control for a second
      cauterization during the period of study. No significant complications of
      infection, perforation, long-term crusting, tattooing or mucocutaneous or
      allergic reactions were identified. CONCLUSIONS: Bilateral epistaxis can be
      treated at a single visit with bilateral silver nitrate therapy in children. This
      treatment is highly effective, well-tolerated, and appears to have a low rate of
      complications.

PMID- 16621036
TI  - Comparison of RNA extraction methods for the detection of porcine reproductive
      and respiratory syndrome virus from boar semen.
AB  - To detect Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) in semen,
      various RNA extraction techniques have been utilized for RT-PCR, but rarely
      compared, to determine an optimized extraction protocol. Due to the viscosity,
      non-homogeneity, high cellularity and large volume of boar semen produced,
      difficulties can be encountered in obtaining RNA from the seminal cell fraction.
      This study compared six RNA extractions, five which used a commercially available
      kit (RNeasy, Qiagen Inc.) for use on highly cellular samples and a traditional
      phenol/chloroform procedure. All extractions were compared on serially diluted
      PRRSV "spiked" seminal cell fractions. The two methods resulting in recovery of
      the highest amount of RNA, which included a Qiashredder (Qiagen Inc.) (protocol
      1) or cell lysis/centrifugation technique (protocol 3) preceding the RNeasy
      procedure were then compared using naturally infected semen samples from
      experimentally infected boars. Both protocols detected similar amounts of virus
      in "spiked" samples, but protocol 1 detected eight additional PRRSV-positive
      semen samples in naturally infected semen. This study demonstrated that semen
      "spiked" with PRRSV (cell-free virus) may not be representative of naturally
      infected semen samples (cell associated virus) for comparing extraction
      protocols, but did identify a useful extraction technique for boar semen.

PMID- 16621037
TI  - Enhancement of the infectivity of SARS-CoV in BALB/c mice by IMP dehydrogenase
      inhibitors, including ribavirin.
AB  - Because of the conflicting data concerning the SARS-CoV inhibitory efficacy of
      ribavirin, an inosine monophosphate (IMP) dehydrogenase inhibitor, studies were
      done to evaluate the efficacy of ribavirin and other IMP dehydrogenase inhibitors
      (5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR), mizoribine, and
      mycophenolic acid) in preventing viral replication in the lungs of BALB/c mice, a
      replication model for severe acute respiratory syndrome (SARS) infections
      (Subbarao, K., McAuliffe, J., Vogel, L., Fahle, G., Fischer, S., Tatti, K.,
      Packard, M., Shieh, W.J., Zaki, S., Murphy, B., 2004. Prior infection and passive
      transfer of neutralizing antibody prevent replication of severe acute respiratory
      syndrome coronavirus (SARS-CoV) in the respiratory tract of mice. J. Virol. 78,
      3572-3577). Ribavirin given at 75 mg/kg 4 h prior to virus exposure and then
      given twice daily for 3 days beginning at day 0 was found to increase virus lung
      titers and extend the length of time that virus could be detected in the lungs of
      mice. Other IMP dehydrogenase inhibitors administered near maximum tolerated
      doses using the same dosing regimen as for ribavirin were found to slightly
      enhance virus replication in the lungs. In addition, ribavirin treatment seemed
      also to promote the production of pro-inflammatory cytokines 4 days after
      cessation of treatment, although after 3 days of treatment ribavirin inhibited
      pro-inflammatory cytokine production in infected mice, significantly reducing the
      levels of the cytokines IL-1alpha, interleukin-5 (IL-5), monocyte chemotactic
      protein-1 (MCP-1), and granulocyte-macrophage colony stimulating factor (GM-CSF).
      These findings suggest that ribavirin may actually contribute to the pathogenesis
      of SARS-CoV by prolonging and/or enhancing viral replication in the lungs. By not
      inhibiting viral replication in the lungs of infected mice, ribavirin treatment
      may have provided a continual source of stimulation for the inflammatory response
      thought to contribute to the pathogenesis of the infection. Our data do not
      support the use of ribavirin or other IMP dehydrogenase inhibitors for treating
      SARS infections in humans.

PMID- 16621038
TI  - Ribonucleotide reductase inhibitors as anti-herpes agents.
AB  - Ribonucleotide reductases (RNRs) supply the 2'-deoxyribonucleotide building
      blocks for DNA synthesis in mammalian cells and for herpes viruses. The viral
      encoded RNRs have unique protein sequences that differ from mammalian enzyme
      primary structures. Selective inhibition of a viral RNR might provide an approach
      to new anti-herpes agents with minimal effects on the mammalian host RNRs. This
      review summarizes efforts to develop anti-herpes agents that selectively target
      viral-encoded RNRs.

PMID- 16621039
TI  - Oligonucleotides as antivirals: dream or realistic perspective?
AB  - Many reports have been published on antiviral activity of synthetic
      oligonucleotides, targeted to act either by a true antisense effect or via non
      sequence specific interactions. This short review will try to evaluate the
      current status of the field by focusing on the effects as reported for inhibition
      of either HSV-1, HCMV or HIV-1. Following an introduction with a historical
      background and a brief discussion on the different types of constructs and
      mechanisms of action, the therapeutic potential of antisense oligonucleotides as
      antivirals, as well as possible pitfalls upon their evaluation will be discussed.

PMID- 16621040
TI  - Antiviral drug resistance.
AB  - Almost 30 years ago it was proposed that the selection for antiviral drug
      resistance should be used as an indicator of antiviral drug activity. In addition
      to discriminating between cellular toxicity and specific activity directed
      against a viral target, drug resistant mutants have been used to confirm the
      mechanism of action of antiviral drugs, to discover the functions of several
      viral proteins and to provide insights into viral evolution and fitness. Drug
      resistance has also become a standard component of both the preclinical and
      clinical drug development process. For HIV and increasingly for other viruses
      drug resistance testing has become standard-of-care in clinical practice. A few
      selected examples are provided to illustrate each of these points.

PMID- 16621041
TI  - In vitro and in vivo evaluation of isatin-beta-thiosemicarbazone and marboran
      against vaccinia and cowpox virus infections.
AB  - It has been reported previously that some thiosemicarbazone compounds have
      prophylactic activity against smallpox disease and therapeutic activity against
      vaccinia virus (VV) infections. In these studies, isatin-beta-thiosemicarbazone
      (IBT) and marboran were administered once daily by intraperitoneal (ip) injection
      to mice using 30, 10 or 3 mg/kg for 5 days beginning 24, 48 or 72 h after
      inoculation with VV or cowpox virus (CV). Both compounds were highly effective (p
      < 0.01) at preventing mortality due to VV even when treatment was delayed up to
      72 h postinfection. In CV-infected mice, neither IBT nor Marboran were effective
      in preventing mortality at any dosage tested when administered at 24 h
      postinoculation. Viral replication in liver, spleen and kidney was delayed or
      reduced by 100-to 10,000-fold by 10 mg/kg of marboran, but not IBT, in VV
      infections. Neither compound was effective against CV infection. Neither IBT nor
      marboran treatment of mice cutaneously infected with VV or CV reduced viral
      replication or clinical disease. These results suggest that this class of
      compound has little therapeutic potential for orthopoxvirus infections since the
      in vivo activity against CV, a surrogate virus for variola, is lacking.

PMID- 16621043
TI  - The role of the dorsolateral tegmentum in the control of male sexual behavior: a
      reevaluation.
AB  - The medial preoptic area/anterior hypothalamus (MPOA/AH) plays a key role in the
      control of male sexual behavior. Independently of the type, MPOA/AH lesions
      permanently eliminate male sexual behavior in the rat. The MPOA/AH projects among
      other structures to the dorsolateral tegmentum (DLT). Bilateral electrolytic
      lesions of the DLT or the unilateral electrolytic destruction of the MPOA/HA
      combined with a contralateral electrolytic lesion of the DLT eliminate male
      sexual behavior. In the present experiment, we evaluated if neurotoxic lesions of
      the DLT produce the same behavioral deficits as those observed after electrolytic
      lesions. This would allow us to evaluate if neurons of the DLT or the fibers
      passing through this area are important in the control of male sexual behavior.
      To this aim, sexually experience male rats were tested for socio-sexual behavior,
      partner preference and motor execution in order to determine if the possible
      behavioral changes could be attributed to alterations in sexual motivation or
      motor execution. One week after the bilateral DLT lesions the animals were
      evaluated in the same behavioral tests. The lesions were identified by glial
      fibrillary acidic protein (GFAP) and neuronal nuclear protein (Neu-N)
      immunohistochemistry. No significant consistent effects upon sexual behavior were
      observed in any of the groups, including the group with clear bilateral damage of
      the DLT. A reduction in the percentage of males displaying ejaculation in the
      first post-lesion test was observed for all groups injected with quinolinic acid.
      No effects upon partner preference or motor coordination were observed after the
      lesion in any of the groups. The lack of effect of DLT neurotoxic lesions upon
      mating suggests that neurons of this structure are not involved in the control of
      male sexual behavior.

PMID- 16621042
TI  - Central infusion of ovine CRF (oCRF) potentiates defensive behaviors in CD-1 mice
      in the Mouse Defense Test Battery (MDTB).
AB  - Following intracerebroventricular (i.c.v.) injection of ovine CRF (oCRF), an
      endogenous peptide agonist at both CRF1 and CRF2 receptors, defensive behaviors
      of CD-1 mice were evaluated in the Mouse Defensive Test Battery (MDTB).
      Behavioral measures taken before, during, and after predator (a hand-held
      anesthetized rat) confrontation included exploratory activity, risk assessment,
      avoidance, flight, freezing, defensive threat/attack, and residual emotional
      responses. Both low (0.1 nmol) and high (0.2 nmol) doses of oCRF robustly
      suppressed exploratory activities and increased risk assessment during the
      initial familiarization period. Flight speed and jump escapes when the mouse was
      chased were significantly elevated by the 0.2 nmol dose. Both doses enhanced
      freezing and avoidance to a distant predator when the escape route was blocked.
      The 0.2 nmol dose also potentiated flight responses to a contacting predator in a
      highly confined space. Both oCRF groups traveled shorter distances and exhibited
      less escape attempts following the removal of the threat stimulus. These findings
      indicate that non-selective activation of corticotropin-releasing factor (CRF)
      receptors via ventricular infusion of oCRF potentiates defensive behaviors
      relevant to the demand of specific challenges, generally enhancing the
      predominant defensive behavior in each specific situation.

PMID- 16621044
TI  - Expression pattern of FOS in orexin neurons during sleep induced by an adenosine
      A2A receptor agonist.
AB  - The present study examined the expression pattern of FOS in the hypothalamic
      peptide neurons during the sleep-dominant state induced by an adenosine A2A
      receptor agonist. The control rats, those that received the microdialysis
      perfusion of their ventral striatum with artificial cerebrospinal fluid in the
      dark-active phase, spent 24% of the 90-min period prior to sacrifice in non-rapid
      eye movement (non-REM) sleep and 2.3% of that in REM sleep. These rats exhibited
      FOS, a transcription factor, in 21% of their orexin neurons and in 1.0% of their
      melanin-concentrating hormone (MCH) neurons in the perifornical/lateral
      hypothalamic areas. However, the rats perfused with 50 microM CGS21680, an
      adenosine A2A receptor agonist, spent 60% of the 90-min period prior to sacrifice
      in non-REM sleep and 11% of that in REM sleep. These rats exhibited FOS in 1.7%
      of their orexin neurons and FOS in 0.5% of their MCH neurons. When the sleep
      dominant state was disturbed by mild stimulation and the rats were kept in the
      sleepy state by treatment with a sleep-inducing dose of CGS21680, the rats
      exhibited FOS in 13.3% of their orexin neurons, which percentage was about half
      of that for the control rats. These results suggest that the sleep-promoting
      process induced by this adenosine A2A receptor agonist was associated with a
      decline in the activity of orexin neurons. MCH neurons are not likely to change
      their activities during this sleep-promoting process.

PMID- 16621045
TI  - Cocaine self-administration and locomotor sensitization are not altered in CART
      knockout mice.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide found
      throughout the brain, particularly in the nucleus accumbens (NAcc) and
      hypothalamus. CART was initially discovered and named based on the upregulation
      of its mRNA in the striatum after acute cocaine or amphetamine injection in rats.
      CART is also known to participate in a wider range of physiological functions
      including feeding, anxiety, bone resorption, and insulin regulation. In this
      report, we demonstrate that knockout mice lacking a functional CART gene show
      similar cocaine-induced locomotor sensitization and cocaine self-administration
      to their wild type siblings. Intravenous cocaine self-administration did not
      differ between CART wild type and knockout mice during acquisition, during
      schedules of reinforcement that require higher response ratios, or across a range
      of doses. In conclusion, these data indicate that CART is not integral to the
      effects of psychostimulants in mice lacking CART throughout development, although
      it may play a regulatory role in the intact animal.

PMID- 16621046
TI  - Astrocytic changes in the hippocampus and functional recovery after cerebral
      ischemia are facilitated by rehabilitation training.
AB  - In this study we examined whether astrocytic and basic fibroblast growth factor
      changes after cerebral ischemia can be influenced by rehabilitation training and
      if these changes are associated with functional improvement. After receiving
      either ischemia or sham surgery, male adult Wistar rats were assigned to one of
      two rehabilitation training group: complex environment housing (EC) or paired
      housing as controls (CON). Rats were tested in the water maze after 14 days of
      rehabilitation training. Results showed increased expression of reactive
      astrocytes (GFAP) in all ischemic animals and in the sham EC rats with a
      significant overall increased seen in the ischemia EC housed animals. The pattern
      of basic fibroblast growth factor (FGF-2) expression seen was somewhat similar to
      that of GFAP. Behavioral data showed that even though all animals learned to
      perform the water maze task over time, the ischemia CON rats took longer to learn
      the task while all the ischemia EC animals performed as well as the sham groups.
      Regression analysis showed that increased GFAP was able to explain some of the
      variances in the behavioral parameters in the water maze of the ischemia EC rats
      suggesting that the activation of astrocytes in this group probably mediated
      enhanced functional recovery. Lastly, it is possible that the favorable effect of
      astrocyte activation after cerebral ischemia was mediated by FGF-2.

PMID- 16621047
TI  - Voluntary ethanol consumption decreases after the inactivation of central
      acetaldehyde by d-penicillamine.
AB  - Acetaldehyde, the first metabolite of ethanol, may mediate some ethanol-induced
      effects. Previous research in our laboratory has shown that D-penicillamine, an
      inactivation agent for acetaldehyde, is effective in decreasing locomotor
      stimulation and conditioned place preference induced by ethanol in mice. In the
      present study, the effects of D-penicillamine on the voluntary consumption of
      ethanol were assessed. Male rats were offered ethanol under restricted access,
      without food or water deprivation. Daily availability of ethanol was limited to a
      15-min period in the home cages. When the response for 10% ethanol was stable,
      rats received an intraperitoneal (IP) injection of D-penicillamine (0, 25, 50 or
      75 mg/kg) over a 5-day period, given 30 min before exposure to ethanol. In a
      second study we determined the specificity of D-penicillamine effects (50 mg/kg)
      on voluntary sucrose consumption (3%). Another study was conducted to evaluate
      whether IP D-penicillamine (50 mg/kg) alters taste reactivity responses. In the
      final experiment, rats were treated with intracerobroventricular (ICV) infusions
      of D-penicillamine (75 microg) for 5 days before drinking ethanol or sucrose. D
      Penicillamine was found to reduce ethanol intake in a dose-dependent manner.
      Sucrose consumption was also affected by this thiol amino acid. We also
      demonstrated that D-penicillamine produced changes in the ingestive and flavor
      properties of sucrose and ethanol, measured by means of a taste reactivity test.
      When D-penicillamine was administered ICV, only voluntary ethanol consumption was
      modified. These findings indicate that the central inactivation of acetaldehyde
      blocks ethanol intake in rats, and suggest that acetaldehyde plays a key role in
      the motivational properties of ethanol.

PMID- 16621048
TI  - Expression of dyskinetic movements and turning behaviour in subchronic L-DOPA 6
      hydroxydopamine-treated rats is influenced by the testing environment.
AB  - Sensitisation in contralateral turning behaviour and induction of abnormal
      involuntary movements (AIMs) after subchronic intermittent L-DOPA were compared
      for their predictive validity as model of parkinsonian dyskinetic movements. L
      DOPA treatment produced sensitisation in turning behaviour in 6-hydroxydopamine
      lesioned rats, when animals were evaluated in hemispherical bowls but not in
      cages. In contrast, sensitisation in AIMs was obtained both in hemispherical
      bowls and cages. Results provide evidence that the choice of the environment used
      in evaluation of AIMs and turning behaviour is of crucial importance.

PMID- 16621049
TI  - Increased concentration of cerebral kynurenic acid alters stimulus processing and
      conditioned responding.
AB  - Kynurenic acid (KYNA) is a tryptophan metabolite synthesized and released by glia
      and recently shown to be a non-competitive antagonist of alpha7 nicotinic
      acetylcholine receptors at physiologically relevant concentrations, and NMDA
      receptors at higher concentrations. KYNA concentration is elevated in individuals
      with schizophrenia and those with Alzheimer's disease, two populations exhibiting
      cholinergic-related cognitive impairments. The present study investigated the
      effects of elevated KYNA concentration on conditioned stimulus processing in
      rats. For the first 2 days of the experiment, a subset of rats received
      intracerebroventricular infusions of either KYNA (0.1 microM) or vehicle and were
      either returned to the home cage or received non-reinforced presentations of a
      visual stimulus. All rats subsequently received presentations of the same visual
      stimulus followed by food reward during a 6-day training phase. In vehicle
      treated rats, pre-exposure to the visual stimulus reduced orienting behaviour to
      the light (standing on the hind legs and orienting towards the visual stimulus)
      when it was later reinforced (i.e., conditioned orienting). In contrast, pre
      exposure to the visual cue or 2 days of KYNA pretreatment reduced conditioned
      orienting behaviour. Finally, the reduction of orienting in KYNA-treated rats
      following pre-exposure was not as robust as in vehicle-treated rats. These
      results suggest that elevated KYNA levels can alter specific aspects of
      attentional processing of environmental stimuli and are discussed in terms of the
      potential contribution of KYNA to cognitive function and dysfunction.

PMID- 16621050
TI  - Levodopa-induced dyskinesia and rotational behavior in hemiparkinsonian rats:
      independent features or components of the same phenomenon?
AB  - Chronic daily administration of 6.25mg/kg of levodopa in unilaterally 6-OHDA
      lesioned rats did not induce any observable behavioral effects for the first
      12.5+/-2.5 days. Thereafter, levodopa administration induced abnormal involuntary
      movements (AIMs), involving the contralateral limb, head, neck and trunk, along
      with the development of contralateral rotations. AIMs and rotations followed a
      progressively worsening, highly correlated, parallel course. We suggest that
      rotational behavior does not represent a pure antiparkinsonian response, but
      along with levodopa-induced dyskinesia is part of the levodopa-induced motor
      response complications syndrome.

PMID- 16621051
TI  - Dynorphin A (1-13) and responsiveness of the newborn rat to a surrogate nipple:
      immediate behavioral consequences and reinforcement effects in conditioning.
AB  - The role of endogenous opioid system in learning (Pavlovian conditioning) and
      reinforcement was studied in newborn rats by pairing central injection of
      dynorphin A (1-13), an endogenous ligand with high affinity for kappa opioid
      receptors, with a surrogate nipple. For conditioning, the nipple served as the
      conditioned stimulus and dynorphin as the unconditioned stimulus. Dynorphin was
      found to elicit an immediate unconditioned, dose-dependent increase in the
      neonatal responsiveness to a surrogate nipple providing water, an effect
      apparently mediated through the kappa opioid receptors. This immediate effect of
      dynorphin was evident in the context of suckling behavior but not in the context
      of adult-like drinking when water was delivered through an intra-oral cannula.
      One hour after injection, the unconditioned stimulatory effect of dynorphin had
      dissipated and no longer affected responsiveness to the nipple. However, pairing
      of centrally injected dynorphin and suckling on a nipple delivering water
      substantially enhanced responsiveness to a nipple 1h later. This suggested
      conditioning, and hence reinforcement, by the centrally injected dynorphin. The
      conditioned sustained nipple attachment was mediated through both kappa and micro
      opioid receptors. These experiments confirm a central role for the brain opioid
      systems in reinforcement of neonatal behavior on the nipple.

PMID- 16621052
TI  - Rat/mouse hemokinin-1, a mammalian tachykinin peptide, markedly potentiates the
      antinociceptive effects of morphine administered at the peripheral and
      supraspinal level.
AB  - Rat/mouse hemokinin 1 (r/m HK-1) is a mammalian tachykinin peptide whose
      biological functions are not fully understood. Our recent report showed that
      i.c.v. administration of r/m HK-1 could produce dose- and time-related
      antinociceptive effect at nanomole concentration, and naloxone significantly
      antagonized this effect. Thus, we provide indirect evidence favoring a role of
      NK1 supraspinal receptors in the inhibitory control of descending pain pathways,
      a role that seems to partially involve the activation of the endogenous opioid
      systems. Based on this report, the present study was conducted to further
      investigate the direct functional interaction between supraspinal tachykinin (r/m
      HK-1) and opioid systems. The results demonstrate that i.c.v. administration of
      r/m HK-1 (5 nmol/kg) could significantly potentiate the antinociceptive effects
      of morphine which was injected at peripheral and supraspinal level. These
      antinociceptive effects were blocked by prior treatment with the classical opioid
      receptors antagonist naloxone, indicating that the potentiated analgesic response
      is mediated by opioid-responsive neurons. Consistent with previous biochemical
      data, a likely mechanism underlying the peptide-mediated enhancement of opioid
      analgesia may center on the ability of r/m HK-1 to release endogenous opioid
      peptides. We suggest that there may be a cascade amplification mechanism in pain
      modulation when the two agents were co-administrated. The synergistic analgesic
      relationship of morphine and r/m HK-1 established here supports the hypothesis
      that supraspinal tachykinin and peripheral and central opioid systems have a
      direct functional interaction in the modulation of local nociceptive responses.

PMID- 16621053
TI  - Retrosplenial cortex lesions impair water maze strategies learning or spatial
      place learning depending on prior experience of the rat.
AB  - There has been debate whether lesions strictly limited to retrosplenial (RS)
      cortex impair spatial navigation, and how robust and reliable any such impairment
      is. The present study used a detailed behavioral analysis with naive or
      strategies-pretrained rats given RS lesions and trained in a water maze (WM).
      Naive RS lesioned rats failed to acquire the required WM strategies throughout
      training. Strategies-pretrained RS lesioned rats were specifically impaired in
      spatial place memory without a WM strategies impairment. Additional training
      overcame the spatial memory impairment. Thus the behavioral consequences of the
      lesion depend on the specific previous experience of the animal. The use of
      appropriate training and testing techniques has revealed experience-dependant
      dissociable impairments in WM strategies learning and in spatial memory,
      indicating that RS cortex is involved in both forms of learning.

PMID- 16621054
TI  - Coenzyme Q10 modulates cognitive impairment against intracerebroventricular
      injection of streptozotocin in rats.
AB  - Coenzyme Q10 (CoQ10), a peculiar lipophilic antioxidant, is an essential
      component of the mitochondrial electron-transport chain. It is involved in the
      manufacturing of adenosine triphosphate (ATP) and has been linked with improving
      cognitive functions. The present study shows the neuroprotective effect of CoQ10
      on cognitive impairments and oxidative damage in hippocampus and cerebral cortex
      of intracerebroventricular-streptozotocin (ICV-STZ) infused rats. Male Wistar
      rats (1-year old) were infused bilaterally with an ICV injection of STZ (1.5
      mg/kg b.wt., in normal saline), while sham group received vehicle only. After 24
      h, the rats were supplemented with CoQ10 (10 mg/kg b.wt. i.p.) for 3 weeks. The
      learning and memory tests were monitored 2 weeks after the lesioning. STZ-infused
      rats showed the loss of cognitive performance in Morris water maze and passive
      avoidance tests. Three weeks after the lesioning, the rats were sacrificed for
      estimating the contents of thiobarbituric acid reactive substances (TBARS),
      reduced glutathione (GSH), protein carbonyl (PC), ATP and the activities of
      glutathione peroxidase (GPx), glutathione reductase (GR),
      cholineacetyltransferase (ChAT) and acetylcholinesterase (AChE). Significant
      alteration in the markers of oxidative damage (TBARS, GSH, PC, GPx and GR) and a
      decline in the level of ATP were observed in the hippocampus and cerebral cortex
      of ICV-STZ rat. A significant decrease in ChAT activity and a concomitant
      increase in AChE activity were observed in the hippocampus. However,
      supplementation with CoQ10 in STZ-infused rats reversed all the parameters
      significantly. Thus, the study demonstrates that CoQ10 may have a therapeutic
      importance in the treatment of Alzheimer's type dementia.

PMID- 16621055
TI  - Interleukin-1beta induces anorexia but not spatial learning and memory deficits
      in the rat.
AB  - Sickness behaviors are a set of adaptive responses to infection that include
      lethargy, anorexia, and, of direct relevance to this work, learning and memory
      impairments. The proinflammatory cytokine, interleukin-1 beta (IL-1beta) has been
      proposed as the primary peripheral mediator of these sickness behaviors, though
      few studies have investigated the effects of peripheral IL-1beta on learning and
      memory. We used three different versions of the Morris water task (Morris water
      task), a spatial learning and memory task, to separately assess the effects of
      peripheral IL-1beta on acquisition, consolidation, and retention of spatial
      location information. Using a dose that induced anorexia, assessed as a
      significant reduction in body weight, we observed no performance impairments in
      the IL-1beta-treated rats across the different versions of the task, suggesting
      that peripheral IL-1beta alone is insufficient to induce spatial learning and
      memory impairments in the rat. The observed dissociation of anorexia and
      cognitive dysfunction suggests that, either spatial learning and memory are not
      principal components of the sickness response, or cognitive dysfunction requires
      different or additional peripheral mediator(s).

PMID- 16621056
TI  - Baboons communicate with their right hand.
AB  - Humans are mainly right-handed for many actions including gestures. This bias is
      strongly linked to a left cerebral hemispheric dominance for language functions.
      Whether similar lateralized systems for communicative behaviors are present in
      other animals is unclear. Here we report the first evidence of strong population
      level right-handedness in 60 captive baboons for a species-specific communicative
      manual gesture. Our findings support the view that lateralization for language
      may have evolved from a gestural system of communication controlled by the left
      hemisphere.

PMID- 16621057
TI  - Intermale aggression in corticotropin-releasing factor receptor 1 deficient mice.
AB  - The anxiogenic neuropeptide, corticotropin-releasing factor (CRF), has a complex
      effect on intermale aggression. CRF receptor 1 (CRFR1) is the primary receptor
      for CRF and in this study, we examined in detail isolation-induced intermale
      aggression in CRFR1 deficient mice. All mice contained a mixed 50:50
      inbred/outbred background to improve aggressive performance. Mice were isolated
      for 4 weeks prior to 2 consecutive days of aggression testing using the resident
      intruder paradigm. Mice were also tested for anxiety on the elevated plus maze.
      Relative to littermate wild-type (WT) controls, CRFR1-mutant mice exhibited
      normal levels of intermale aggression over the 2 test days in terms of percentage
      showing aggression, number of attacks, time aggressive, and latency to first
      attack. In terms of sites of attacks on intruders, CRFR1-deficient mice attacked
      the ventral portion of the mid-section (including belly) significantly less
      frequently than WT males on test day 1, but these differences did not reach
      significance on test day 2. No other differences in sites of attacks were
      observed. Tail rattling also did not differ between groups. Importantly, KO males
      showed decreased anxiety relative to WT mice (consistent with previous reports)
      as evidenced by spending significantly more time on the open arms and
      significantly less time on the closed arms of the elevated plus maze. Plus maze
      performance did not correlate with any measure of levels of aggression,
      suggesting a dissociation between altered levels of anxiety and aggressive
      performance. Taken together, the results suggest that the activation CRFR1 is not
      necessary for the normal production of isolation-induced intermale aggression.

PMID- 16621058
TI  - Association of paradoxical sleep deprivation and ecstasy (MDMA) enhances genital
      reflexes in male rats.
AB  - Ecstasy ((+/-)3,4-methylenedioxymethamphetamine, MDMA) is a psychostimulant and a
      synthetic derivative of amphetamine that, according to its consumers, promotes
      the enhancement of sexual pleasure. This study sought to investigate the effects
      of ecstasy in the genital reflexes of paradoxical sleep deprived (PSD) male rats.
      Distinct groups of PSD rats were administered with saline or different doses of
      ecstasy. The incidence of genital reflexes was verified for 100 min. The four
      doses that were used induced genital reflexes in PSD animals and these
      significantly differed from their respective treated control groups. Under the
      influence of two intermediary doses (2.5 and 5mg/kg), all animals displayed
      erection and ejaculation. The frequency of genital reflexes was also
      significantly greater than in relation to the PSD-saline group. The comparison
      between cocaine and ecstasy in PSD rats revealed that ecstasy induced more
      erections and ejaculations than cocaine. Thus, the present results showed a great
      enhancement of the genital reflexes of PSD rats that might have occurred due to
      serotoninergic alterations induced by this illicit substance when associated to
      sleep deprivation.

PMID- 16621059
TI  - Toxicity of silver to two freshwater algae, Chlamydomonas reinhardtii and
      Pseudokirchneriella sub-capitata, grown under continuous culture conditions:
      influence of thiosulphate.
AB  - In a test of the biotic ligand model (BLM), the uptake and toxicity of silver, in
      the absence or presence of the inorganic ligand, thiosulphate, were assessed for
      two freshwater green algae, Chlamydomonas reinhardtii and Pseudokirchneriella sub
      capitata, using turbidostat continuous cultures. In the initial experiments, run
      in the absence of thiosulphate, the influent Ag concentration was varied from 0
      to 75 nM in steps; for each influent concentration, silver uptake was calculated
      and the algal growth rate was determined. Silver uptake rates at low Ag
      concentrations were similar for both algae (e.g., 14-19 nmolm(-2)h(-1), for
      influent Ag(+) concentrations of approximately 9 nM) but at higher exposures
      uptake by P. sub-capitata exceeded that of C. reinhardtii. Despite this higher
      uptake rate, in the absence of thiosulphate P. sub-capitata was not more
      sensitive to free silver; 50% growth inhibition was reached at influent free
      Ag(+) concentrations of 15+/-7 and 22+/-13 nM for C. reinhardtii and P. sub
      capitata, respectively. In the second series of experiments, the free Ag(+)
      concentration was held constant ( approximately 9 nM in the influent; 2-3 nM in
      the effluent) while the concentration of the silver thiosulphate complex,
      AgS(2)O(3)(-), was increased from 9 to 90 nM in steps. Under such conditions, the
      BLM would predict that silver uptake and toxicity should remain constant. On the
      contrary, both silver uptake and silver toxicity increased, indicating that the
      anionic silver thiosulphate complex enters the algal cells via a membrane-bound
      sulphate transporter and contributes to uptake and toxicity. However, for both
      algae there were indications that silver assimilated in this manner was somewhat
      less toxic to the algal cell than silver that entered via cation transport only.
      Physiological indicators of stress revealed possible different intracellular
      targets for these two freshwater algae, proteins and enzymes for C. reinhardtii
      and the photosynthetic apparatus for P. sub-capitata.

PMID- 16621060
TI  - Comparison of protein expression in plasma from nonylphenol and bisphenol A
      exposed Atlantic cod (Gadus morhua) and turbot (Scophthalmus maximus) by use of
      SELDI-TOF.
AB  - The overall objective of this study was to compare the expression of plasma
      proteins in juvenile cod and turbot after a 3 week exposure to two different
      chemicals known to be estrogenic: 4-nonylphenol (NP, 29 microg/L) and bisphenol A
      (BPA, 59 microg/L). ProteinChip) array technology in combination with surfaced
      enhanced laser desorption ionisation-time of flight (SELDI-TOF) was used to
      investigate general responses in plasma proteins. In addition, an indirect enzyme
      linked immunosorbent assay (ELISA) was used to analyse two specific biomarkers of
      estrogenic exposure, vitellogenin (Vtg) and zona radiata protein (Zrp) in plasma.
      Both methods revealed clear species specific responses. In cod, 67% of
      significantly altered proteins showed the same response (up or down regulated) in
      NP and BPA exposed animals (males and females combined). The rest were either
      specific to NP (10%), BPA (19%) or they showed opposite responses to the two
      chemicals (4%). In contrast, only 20% of significantly altered proteins were
      common for NP and BPA exposed turbot: 60% were altered only in NP and 17% only in
      BPA. Furthermore, in BPA exposed cod, 77% of the responses were common for male
      and females, whereas turbot showed only 21% similarity for the two genders.
      However, NP exposed male and female turbot showed 88% similarity in responses. As
      gender was not determined in NP exposed cod, gender specific responses could not
      be determined. ELISA results supported that cod responded clearly to both
      chemicals as a large increase was observed in Vtg and Zrp levels. Turbot
      responded strongly to NP, but seemed only slightly affected by BPA. Overall, the
      results indicated that cod are more sensitive or respond with less specificity to
      estrogenic chemicals than turbot. The relatively large degree of common responses
      in NP and BPA exposed cod may indicate that in cod BPA have similar mode of
      action as NP. Generally, the results show the potential of SELDI-TOF as a tool
      for comparing multiple responses, and for identifying exposure as well as gender
      specific responses.

PMID- 16621061
TI  - Community ecotoxicology: invertebrate emergence from Fire Trol 934 contaminated
      vernal pool and salt marsh sediments under contrasting photoperiod and
      temperature regimes.
AB  - Fire retardant chemicals are being used increasingly throughout the world to
      effectively manage wildland fires. The widespread use and high volume of
      retardant products being applied increase the potential for contamination of
      temporary wetlands that represent critical habitat for numerous species. This
      study aimed at assessing the emergence response of invertebrates from fire
      retardant-contaminated sediments derived from two temporary wetlands, a vernal
      pool and a salt marsh, which differ distinctly in their invertebrate resting egg
      bank structure. Two application rates (1 and 3 Lm(-2)) of the commercially
      available fire retardant, Fire Trol 934, were used to simulate environmentally
      realistic contamination scenarios for wetlands situated in Mediterranean
      grasslands and shrublands, respectively. Two contrasting emergence conditions
      (winter versus spring flooding conditions) were simulated to take into account
      the high inter- and intra-annual variability of pond filling in Mediterranean
      areas. Results showed a decrease in abundance (p<0.001), taxonomic richness
      (p<0.001) and biodiversity based on Shannon-Weaver diversity indices (p<0.001) in
      both wetlands and under both emergence conditions with increased retardant
      application rate. This was due to the loss of chydorids, daphnids, ostracods, and
      rotifers in the vernal pool, and rotifers, nematodes, protozoa and aquatic fungi
      in the salt marsh. The observed patterns were similar for many taxa and community
      metrics at either retardant level irrespective of hatching regime, suggesting
      that the timing of pond filling was generally not an important influence in
      community response to Fire Trol. A multivariate approach to characterize
      community structure suggests that wetlands that undergo periodic drying are
      resilient to perturbations by chemicals and that community responses to
      anthropogenic stressors may be well within the range of response to natural
      disturbances.

PMID- 16621062
TI  - Effects of estuarine sediment contamination on feeding and on key physiological
      functions of the polychaete Hediste diversicolor: Laboratory and in situ assays.
AB  - This study aimed at integrating postexposure feeding and some biochemical
      parameters in the responses of the estuarine polychaeta, Hediste diversicolor, to
      controlled laboratory exposure conditions and to in situ exposures scenario of
      sediment contamination. Since H. diversicolor feeding may be considered as a
      major rate-limiting step in the processing of detritus in European estuaries, a
      reduction in feeding activity may have implications not only at the individual
      and population level of the species but also in detritus processing and in
      organic matter decomposition rates at the ecosystem level. The biochemical
      parameters were chosen as indicators of four key physiological functions:
      neurotransmission, metabolic condition, detoxification processes and antioxidant
      defences. The Mira and Sado estuaries, located in the Southwest coast of Portugal
      and classified as undisturbed and impacted, respectively, were selected as sites
      for this study. A significant depression in H. diversicolor postexposure feeding
      (from 30 to 70%) was consistently detected in all impacted sediments, supporting
      the sensitivity and responsiveness of feeding as a sublethal toxicity endpoint.
      Alongside with a reduced energy intake, an increased rate of organisms' anaerobic
      metabolism, as evidenced by an enhancement of lactate dehydrogenase activity (up
      to 1.5-fold), suggested a rapid need of additional energy to ameliorate chemical
      stress. Moreover, oxidative stress was shown to be an important mechanism of
      toxicity of the impacted sediments in H. diversicolor, as evidenced by a marked
      reduction in the glutathione redox status (up to 6.5-fold) and an increase in
      lipid peroxides levels (up to 2.3-fold) in organisms exposed to the most impacted
      sediments. Results of the in situ assay, conducted to assess the ecological
      relevance of sediment laboratory toxicity estimates and their application to make
      valid field extrapolations, revealed a lack of agreement in the response of
      catalase in organisms exposed to moderate impacted sediments. Our results support
      the utility of integrating responses at individual and sub-individual level to
      evaluate potential toxicant-induced changes in key physiological functions of H.
      diversicolor and to interpret their potential ecological consequences.

PMID- 16621063
TI  - Effects of North Sea oil and alkylphenols on biomarker responses in juvenile
      Atlantic cod (Gadus morhua).
AB  - A consequence of oil drilling at sea is the release of produced water
      contaminated with e.g. polycyclic aromatic hydrocarbons (PAH) and alkylphenols.
      In the present study, juvenile Atlantic cod were exposed to North Sea oil,
      nonylphenol and a combination of the North Sea oil and an alkylphenol mixture in
      a flow-through system. A suite of hepatic biomarkers were analysed. Exposure to
      North Sea oil resulted in strong induction of CYP1A protein levels and EROD
      activities. Exposure to nonylphenol, on the other hand, resulted in decreased
      CYP1A levels and EROD activities. Thus, nonylphenol appears to down-regulate
      CYP1A expression in Atlantic cod. Combined exposure to North Sea oil with an
      alkylphenol mixture resulted in lower EROD induction, compared to that in fish
      exposed to North Sea oil alone. This difference was not statistically
      significant, but still we believe that the alkylphenols have inhibited CYP1A
      activities in the fish which may have compromised CYP1A mediated metabolism of
      other xenobiotics, including PAH. CYP3A protein levels were lower, compared to
      controls, in fish exposed to nonylphenol and the combination of North Sea oil and
      alkylphenol mixture. In contrast, the oil alone had no effect on CYP3A protein
      content. North Sea oil exposure, alone or in combination with alkylphenols,
      caused oxidative stress observed as elevated levels of GSSG content and GR and
      CAT activities. Interestingly, exposure to nonylphenol resulted in a marked
      depletion of total glutathione levels. This apparent depletion may be a
      consequence of increased conjugation of glutathione to nonylphenol followed by
      excretion. An increase in conjugation enzyme GST activity was observed in the
      nonylphenol exposed group, although the difference was not significant. No sign
      of oxidative damage, measured as lipid peroxidation, was observed in any of the
      exposures experiments. This study suggests that North Sea oil may lead to
      oxidative stress and altered CYP1A and CYP3A expression. Alkylphenols, present in
      produced water, resulted in decreased CYP1A and CYP3A protein expression in
      Atlantic cod.

PMID- 16621064
TI  - Biotransformation of polychlorinated biphenyls (PCBs) and bioformation of
      hydroxylated PCBs in fish.
AB  - Hydroxylated PCBs (OH-PCBs) are a class of organic contaminants that have been
      found recently in the plasma of Great Lakes fish, the source of which is either
      bioformation from PCBs or accumulation from the environment. To address the
      potential for fish to biotransform PCBs and bioform OH-PCBs juvenile rainbow
      trout (Oncorhynchus mykiss; approximately 80 g) were exposed to dietary
      concentrations of an environmentally relevant mixture of PCBs. Eight OH-PCBs were
      found in the plasma of rainbow trout after 30 days of exposure to the PCBs, the
      relative pattern of which was similar to those observed in wild lake trout
      (Salvelinus namaycush) from Lake Ontario. Hydroxylated-PCBs were not found
      (detection limit 0.02 pg/g) in the food or control (not PCB-exposed) fish. A
      curvilinear logt(1/2)-logK(ow) relationship for recalcitrant PCBs was found,
      similar to previously reported relationships, although t(1/2) values were longer
      and shorter than studies using smaller fish or cooler temperatures, respectively.
      A number of PCB congeners fell below the logt(1/2)-logK(ow) relationship
      providing the first estimates of non-chiral PCB biotransformation rates in fish.
      Enantioselective degradation of the chiral congeners PCBs 91 and 136, also
      indicated biotransformation. Biotransformation of PCBs was structure-dependent
      with greater biotransformation of PCBs with vicinal hydrogen atoms in the
      meta/para positions, suggesting CYP 2B-like biotransformation. Other chiral
      congeners with a meta/para substitution pattern showed no enantioselective
      degradation but were biotransformed based on the logt(1/2)-logK(ow) relationship.
      The results of this study demonstrate that laboratory held rainbow trout can
      biotransform a number of PCB congeners and that bioformation is likely an
      important source of OH-PCBs in wild salmonids of the Great Lakes.

PMID- 16621065
TI  - Dramatic reorganisation of Trichomonas endomembranes during amoebal
      transformation: a possible role for G-proteins.

PMID- 16621066
TI  - Cloning and preliminary characterization of the dihydroorotase from Toxoplasma
      gondii.
AB  - A full-length dihydroorotase (DHOase) sequence was cloned from a Toxoplasma
      gondii tachyzoite cDNA library. The sequence had a calculated molecular mass of
      44.2 kDa and a pI of 5.72, and was most similar to type IIa DHOases. A
      recombinant protein was expressed and purified with a yield of approximately 20
      mg L(-1) of cell culture. Polyclonal antibodies raised against purified
      recombinant protein reacted with a band of the expected molecular mass in
      tachyzoite extracts. Specific activities of 18.3 micromol/min/mg in the
      biosynthetic direction and 18.4 micromol/min/mg in the degradative direction,
      with K(m, carbamyl aspartate) = 323 microM and K(m, dihydroorotate) = 64.3
      microM, were measured for purified recombinant protein. Size exclusion
      chromatography/laser light scattering showed a single, monodisperse peak with a
      molecular mass of 45.6 kDa, suggesting that the native protein is a monomer.

PMID- 16621067
TI  - Disguising itself--insights into Plasmodium falciparum binding and immune evasion
      from the DBL crystal structure.
AB  - Duffy-binding like (DBL) domains are common to two different families of malaria
      proteins that are involved in parasite invasion of erythrocytes or cytoadhesion
      of infected erythrocytes. DBL domain crystal structures have recently been solved
      for two different erythrocyte binding ligands, EBA-175 and the Plasmodium
      knowlesi alpha Duffy binding protein. These structures reveal different
      mechanisms for DBL binding and erythrocyte invasion. This review summarizes
      recent work on DBL domain binding and immune evasion and proposes a new
      structural model for how these domains adapted to intense antibody surveillance
      at the infected erythrocyte surface.

PMID- 16621068
TI  - Toxoplasma gondii has two lineages of histones 2b (H2B) with different expression
      profiles.

PMID- 16621069
TI  - Characterization of RNA polymerase II subunits of Trypanosoma brucei.
AB  - The Trypanosoma brucei homolog of the RNA polymerase II (RNA Pol II) subunit RPB9
      was cloned and characterized. Contrary to what occurs in Saccharomyces
      cerevisiae, in T. brucei this protein was found to be essential since the knock
      down of its expression by RNAi led to lethality in both bloodstream and procyclic
      forms of the parasite. As expected, TbRPB9 knock down specifically inhibited
      transcription by RNA Pol II, but not by RNA Pol I and III. TbRPB9 was used as
      bait to isolate the RNA Pol II core complex by tandem affinity purification. Nine
      subunits homologous to the other eukaryotic RNA Pol II, namely RPB1, RPB2, RPB3,
      RPB4, RPB5, RPB6, RPB7, RPB8 and RPB11, were identified in the purified complex.
      Interestingly, the RPB5 homolog associated with RNA Pol II was different from the
      one previously found in RNA Pol I. Analysis of the genome database revealed the
      presence of genes for all purified subunits plus RPB10. As in the case of TbRPB5,
      two genes coding for different isoforms of TbRPB6 were identified, suggesting the
      existence of polymerase-specific isoforms for both TbRPB5 and TbRPB6.

PMID- 16621070
TI  - The cyst wall of Entamoeba invadens contains chitosan (deacetylated chitin).
AB  - The cyst wall of Entamoeba invadens (Ei), a model for the human pathogen
      Entamoeba histolytica, contains chitin, which is a homopolymer of beta-1, 4
      linked N-acetyl-glucosamine (GlcNAc). In fungi and in bacteria that make
      nodulation factors, chitin deacetylases make chitosan, which is a mixture of
      GlcNAc and glucosamine and so has a positive charge. The activity of an Ei chitin
      deacetylase was revealed by a 3-4-fold increase in released GlcNAc when
      deproteinated cyst walls were chemically acetylated prior to treatment with a
      commerical chitinase. Because this chitinase releases GlcNAc but not GlcN,
      increases in released GlcNAc after acetylation suggested the presence of chitosan
      in Ei cyst walls. Five putative Ei and Eh chitin deacetylase genes resembled
      those of fungi and bacteria. A predicted Eh chitin deacetylase matched closely
      the three-dimensional structure of a Bacillus subtilis peptiodglycan deacetylase.
      A recombinant Eh chitin deacetylase, expressed in Saccharomyces cerevisiae,
      deacetylated chitooligosaccharides in vitro. These results are consistent with
      the idea that Ei chitin deacetylases modify chitin to produce chitosan in the Ei
      cyst wall.

PMID- 16621071
TI  - Evaluation response and effectiveness of thyroid hormone replacement treatment on
      lipid profile and function in elderly patients with subclinical hypothyroidism.
AB  - Positive effect of thyroid hormone replacement (THR) on lipid profile is well
      defined. Effectiveness of THR on lipid profile and function among elderly
      patients with subclinical hypothyroidism (SCH) has not yet been concluded. This
      is a population-based cross-sectional study. Twenty-six elderly patients with SCH
      were compared with 31 patients with clinical hypothyroidism (CH). Before the
      study neither group had received THR therapy. Data on lipid profile, demographic,
      functional, and cognitive status were obtained at baseline. SCH was defined as an
      elevated thyroid-stimulating hormone (TSH) level (> 4.67 mU/l) and normal serum
      free thyroxine (FT(4)) level. Total cholesterol (TC), high-density lipoprotein
      (HDL) cholesterol, and triglycerides (TG) were measured after overnight fast. The
      level of lower density lipoprotein (LDL) cholesterol was calculated. Both studied
      groups received levothyroxyne replacement and re-evaluated after 3 months of
      euthyroidism. Functional and cognitive status were evaluated by the activity of
      daily living (ADL) and mini mental state evaluation (MMSE), respectively.
      Participants with SCH did not differ from patients with CH regarding age, gender,
      cognitive, and functional status, and prevalence of cardiovascular disease (CD)
      was similar in both groups. Most patients (24/26) with SCH had TSH levels lower
      than 10 mU/l. Response to THR therapy regarding the improvement of blood levels
      of TC, LDL, and TG had a non-significant trend, which seemed to be better in
      patients with SCH than in those with CH. Decreases, TC/HDL and LDL/HDL ratios
      were greater in patients SCH (p < 0.0001 and p = 0.0004, respectively) than in
      patients with CH. Improvement in cognitive and functional status and decrease in
      mean blood pressure and body mass index (BMI) were found in both of studied
      groups. It was shown that THR among patients with SCH is beneficial not only by
      improvement in lipid profile, as well as by improvement in cognitive and
      functional status, but also in decreasing blood pressure and BMI.

PMID- 16621072
TI  - Validation of the Cumulative Illness Rating Scale (CIRS) in hospitalized
      nonagenarians.
AB  - This is a retrospective analysis of patients aged 90-99 years, admitted over a 6
      month period to a district hospital. One hundred three patients were included in
      the study with an average age of 92 years and a male to female ratio of 1:3.
      Fifty-five percent of the patients hospitalized came from nursing care
      facilities. Comparisons were made of patient characteristics from nursing homes
      and the community. The physical burden of illness was measured by the CIRS,
      Illness Severity Index (SI), and Co-morbidity Index (CI). The average length of
      stay was 6.3 days for those from nursing care facilities and 10.2 days from the
      community as compared with 3.3 days for total hospital in-patients. Excluding
      deceased patients there was a significant (p < 0.05) correlation between
      patient's CIRS to length of stay in hospital but was equivocal for SI and CI.
      There were no association between patient's CIRS, SI, and CI to mode of referral
      and residence. The mortality rate for this group was 13% as compared with the
      hospital rate of 10.2%. CIRS, SI, and CI were useful in distinguishing the
      mortally ill from the morbidly ill; otherwise there were no differences, between
      patients who hail from nursing care facilities or from the community and whether
      they were referred by carers, nursing staff, medical practitioners/specialists or
      themselves. There were significant differences in the CIRS scores between
      deceased and survivors indicating CIRS is potentially useful tool in predicting
      outcome. The SI and CI composites performed equally well in predicting outcome.

PMID- 16621073
TI  - Intra- and inter-observer agreement of a protocol for clinical examination of
      dairy cows.
AB  - In 2004,five veterinarians examined 283 dairy cows from four Danish dairy herds
      and independently assigned scores for the clinical signs lameness, hock lesions
      and other cutaneous lesions to each cow using a clinical protocol. We evaluated
      the inter-observer and the intra-observer agreement using prevalence-adjusted,
      bias-adjusted kappa (PABAK). We chose two different cut-offs between the ordinal
      scores for classifying cows as healthy or diseased for each of the clinical
      signs, and we compared the ability of the observers to discriminate between
      healthy and diseased cows for the two cut-offs. Without any formal training of
      the observers we found PABAK in the range 0.36-0.88 and we concluded that the
      choice of cut-off had an effect on the observed agreement among the observers.

PMID- 16621074
TI  - Gene patents, health care policy and licensing schemes.
AB  - Human gene patents continue to stir social controversy, including the possibility
      that they might adversely affect public access to useful technologies. It has
      been suggested that a compulsory licensing policy might be used to alleviate the
      adverse effect of patents in this context. We suggest, however, that it is
      unclear whether existing international policies and licensing practices will
      permit compulsory licensing to be used in a way that would address common
      concerns. Indeed, given the minor role that genetic technologies have in most
      health care systems, it would be difficult to justify compulsory licensing. At a
      minimum, policy makers need to be more realistic about the potential effects of
      international trade agreements on the development of biotechnology policies.

PMID- 16621075
TI  - More optimal dose distributions for moving lung tumours: a planning study.
AB  - BACKGROUND AND PURPOSE: Target volumes for moving lung tumours encompass the full
      range of respiratory motion, increasing the risk of lung complications. Intensity
      modulated radiotherapy (IMRT) allows for more precise dose distributions.
      Distributions corresponding to the probability density function (PDF) of tumour
      motion may better spare lung yet deliver adequate target dose. The planning study
      purpose is to compare and evaluate different dose distributions on a moving lung
      tumour: (A) conformal RT (CRT) encompassing the full range of tumour motion, (B)
      CRT encompassing the modal tumour position only, and (C) an IMRT technique where
      the dose delivered corresponds to the tumour PDF. MATERIALS AND METHODS: A 5 cm
      diameter spherical target within a rectangular lung equivalent phantom was
      treated using a parallel-opposed pair technique with a 1.5 cm margin around the
      tumour (in the beam's eye view). Asymmetrical sinusoidal (superior-inferior)
      target movement (peak-trough = 3 cm) was simulated for different dose
      distributions (prescription dose = 60 Gy). Equivalent uniform dose (EUD) for the
      tumour and normal tissue complication probabilities (NTCPs) for radiation
      pneumonitis were evaluated. RESULTS: The EUDs were 60.0, 48.5, and 57.9 Gy while
      the NTCPs were 5, 1, and 3% for cases A, B, and C, respectively (assuming
      survival fraction, SF(2)(Gy) = 0.5). CONCLUSIONS: Since these results rely on
      unvalidated radiobiologic models, they must be interpreted cautiously. However,
      more optimized dose distributions for moving lung targets appear feasible and can
      reduce lung complications with only a negligible impact on the expected EUD and,
      thus, deserve further study.

PMID- 16621076
TI  - Daily organ tracking in intensity-modulated radiotherapy of prostate cancer using
      an electronic portal imaging device with a dose saving acquisition mode.
AB  - BACKGROUND AND PURPOSE: Daily use of conventional electronic portal imaging
      devices (EPID) for organ tracking is limited due to the relatively high dose
      required for high quality image acquisition. We studied the use of a novel dose
      saving acquisition mode (RadMode) allowing to take images with one monitor unit
      per image in prostate cancer patients undergoing intensity-modulated radiotherapy
      (IMRT) and tracking of implanted fiducial gold markers. PATIENTS AND METHODS:
      Twenty five patients underwent implantation of three fiducial gold markers prior
      to the planning CT. Before each treatment of a course of 37 fractions, orthogonal
      localization images from the antero-posterior and from the lateral direction were
      acquired. Portal images of both the setup procedure and the five IMRT treatment
      beams were analyzed. RESULTS: On average, four localization images were needed
      for a correct patient setup, resulting in four monitor units extra dose per
      fraction. The mean extra dose delivered to the patient was thereby increased by
      1.2%. The procedure was precise enough to reduce the mean displacements prior to
      treatment to < o =0.3 mm. CONCLUSIONS: The use of a new dose saving acquisition
      mode enables to perform daily EPID-based prostate tracking with a cumulative
      extra dose of below 1 Gy. This concept is efficiently used in IMRT-treated
      patients, where separation of setup beams from treatment beams is mandatory.

PMID- 16621077
TI  - Sensorimotor postural rearrangement after unilateral vestibular deafferentation
      in patients with acoustic neuroma.
AB  - Unilateral vestibular lesion, as acoustic neuroma and its surgical removal, leads
      to impaired balance control. After initial vertigo and postural instability
      corresponding to unilateral vestibular deafferentation, improvement in symptoms
      and global balance functions occurs by a process called vestibular compensation.
      In this respect, this prospective study aimed to assess the differential
      contribution of sensory inputs to the regulation of posture during the recovery
      process after acoustic neuroma removal. Twenty-seven patients with acoustic
      neuroma underwent vestibular and posturographic testings, shortly before and 8
      days, 1 month and 3 months after surgical removal of the tumour. Immediately
      after vestibular deafferentation, vestibular function was asymmetrical, postural
      performances were altered, especially in eyes closed conditions and in sensory
      challenged situations. One month, and more particularly 3 months after surgery,
      restoration and even improvement of vestibular and balance performances occurred,
      associated with a lower number of falls, development of more appropriate
      sensorimotor strategies and better resolution of sensorial conflicts. Postural
      perturbations are related to erroneous vestibular afferences, leading to
      incoherence in information about head position and interference with
      somatosensory and visual pathways. The time-course implementation of central
      adaptive mechanisms, characterized by substitution by other sensory afferences
      and new behavioural strategies, leads to an improvement of balance performance.

PMID- 16621078
TI  - Substantial role of locus coeruleus-noradrenergic activation and capsaicin
      insensitive primary afferent fibers in bee venom's anti-inflammatory effect.
AB  - Several lines of evidence indicate significant interactions between the immune
      and nervous systems. Our recent study reveals that 'bee venom (BV) induced anti
      inflammatory effect' (BVAI) was produced by sympathetic preganglionic neuronal
      activation and subsequent adrenomedullary catecholamine release in a zymosan
      induced inflammation model. However, the specific peripheral input and the
      supraspinal neuronal systems that are involved in this BVAI remain to be defined.
      Here we show that subcutaneous BV injection into left hind limb significantly
      reduces zymosan-induced leukocyte migration and that this effect is completely
      inhibited by denervation of the left sciatic nerve. This BVAI was not affected by
      the destruction of capsaicin-sensitive primary afferent fibers using either
      neonatal capsaicin or resiniferatoxin (RTX) pretreatment. BV injection into the
      left hind limb significantly increased Fos expression in the contralateral locus
      coeruleus (LC) in non-inflamed mice. In zymosan-inflamed mice, BV injection
      produced a further increase in LC Fos expression as compared with non-inflamed
      mice. This BV-induced Fos increase in the LC was not affected by RTX
      pretreatment. Pharmacological blockage of central noradrenergic activity by
      either central chemical sympathectomy (i.c.v. 6-hydroxydopamine) or alpha2
      adrenoceptor antagonism (i.c.v. idazoxan) completely blocked BVAI. Taken
      together, these results suggest that BVAI is mediated by peripheral activation of
      capsaicin-insensitive primary afferent fibers and subsequent central
      noradrenergic activation including the LC.

PMID- 16621079
TI  - Transcription factors in glutamatergic neurogenesis: conserved programs in
      neocortex, cerebellum, and adult hippocampus.
AB  - Glutamatergic, pyramidal-projection neurons are produced in the embryonic
      cerebral cortex by a series of genetically programmed fate choices, implemented
      in large part by developmental transcription factors. Our work has focused on
      Pax6, Tbr2/Eomes, NeuroD, and Tbr1, which are expressed sequentially during the
      neurogenesis of pyramidal-projection neurons. Recently, we have found that the
      same transcription factors are expressed, in the same order, during glutamatergic
      neurogenesis in the adult dentate gyrus, and (with modifications) in the
      developing cerebellum. While the precise functional significance of this
      transcription factor expression sequence is unknown, its common appearance in
      embryonic and adult neurogenesis, and in different brain regions, suggests it is
      part of a conserved genetic program that specifies general properties of
      glutamatergic neurons in these regions. Subtypes of glutamatergic neurons (e.g.,
      layer-specific fates in the cortex) are further determined by combinations of
      transcription factors, superimposed on general sequential programs. These new
      perspectives on neurogenesis add to the conceptual framework for strategies to
      engineer neural stem cells for the repair of specific brain circuits.

PMID- 16621080
TI  - In situ detoxification and continuous cultivation of dilute-acid hydrolyzate to
      ethanol by encapsulated S. cerevisiae.
AB  - Dilute-acid lignocellulosic hydrolyzate was successfully fermented to ethanol by
      encapsulated Saccharomyces cerevisiae at dilution rates up to 0.5h(-1). The
      hydrolyzate was so toxic that freely suspended yeast cells could ferment it
      continuously just up to dilution rate 0.1h(-1), where the cells lost 75% of their
      viability measured by colony forming unit (CFU). However, encapsulation increased
      their capacity for in situ detoxification of the hydrolyzate and protected the
      cells against the inhibitors present in the hydrolyzate. While the cells were
      encapsulated, they could successfully ferment the hydrolyzate at tested dilution
      rates 0.1-0.5h(-1), and keep more than 75% cell viability in the worst
      conditions. They produced ethanol with yield 0.44+/-0.01 g/g and specific
      productivity 0.14-0.17 g/(gh) at all dilution rates. Glycerol was the main by
      product of the cultivations, which yielded 0.039-0.052 g/g. HMF present in the
      hydrolyzate was converted 48-71% by the encapsulated yeast, while furfural was
      totally converted at dilution rates 0.1 and 0.2h(-1) and partly at the higher
      rates. Continuous cultivation of encapsulated yeast was also investigated on
      glucose in synthetic medium up to dilution rate 1.0 h(-1). At this highest rate,
      ethanol and glycerol were also the major products with yields 0.43 and 0.076 g/g,
      respectively. The experiments lasted for 18-21 days, and no damage in the
      capsules was detected.

PMID- 16621081
TI  - Protein activity in bacterial inclusion bodies correlates with predicted
      aggregation rates.
AB  - Recent data show that protein aggregation as bacterial inclusion bodies does not
      necessarily imply loss of biological activity. Here, we investigate the effect of
      a large set of single-point mutants of an aggregation-prone protein on its
      specific activity once deposited in inclusion bodies. The activity of such
      aggregates significantly correlates with the predicted aggregation rates for each
      mutant, suggesting that rationally tuning the kinetic competition between folding
      and aggregation might result in highly active, inclusion bodies. The exploration
      of this technology during recombinant protein production would have a significant
      biotechnological value.

PMID- 16621082
TI  - Efficient generation of insect-based cell-free translation extracts active in
      glycosylation and signal sequence processing.
AB  - A novel method for generation of insect-based cell-free translation extracts is
      presented. The protocol can be completed in less than an hour, and the resulting
      extracts are extremely proficient in N-linked glycosylation and signal sequence
      processing. No specialized equipment other than that usually present in an
      ordinary biochemistry laboratory is required. The novel approach dramatically
      reduces cost and time while rendering enhanced lysates compared to previously
      published strategies.

PMID- 16621083
TI  - Insights into extreme thermoacidophily based on genome analysis of Picrophilus
      torridus and other thermoacidophilic archaea.
AB  - Thermoacidophiles are prokaryotic microorganisms with the stunning capability to
      survive and multiply at extremely low pH and simultaneously at high temperatures.
      The mechanisms by which these organisms, exclusively members of the Archaea, cope
      with their harsh surroundings are poorly understood. The genome sequences of
      several representatives of the thermoacidophilic genera Picrophilus, Thermoplasma
      and Sulfolobus have recently become available. Genome-wide comparison has
      revealed a number of features as possible facets of the overall acidophilic
      survival strategy of the most thermoacidophilic organisms known, such as a high
      ratio of secondary over primary transport systems, the composition of the
      respiratory chain, and the frequent genetic input via lateral gene transfer (LGT)
      during evolution.

PMID- 16621084
TI  - A novel in vitro filter trap assay identifies tannic acid as an amyloid
      aggregation inducer for HET-s.
AB  - In this work we present an easy and low cost in vitro filter trap assay to
      quickly identify direct actors on amyloid prion aggregation. We chose the
      recombinant purified prion protein HET-s from Podospora anserina as a reference.
      HET-s was labelled with a fluorophore prior to aggregation assays in a 96 well
      micro-array system. Aggregation assays were carried out in presence of a number
      of chemical compounds, followed by a filter trap assay through a cellulose
      acetate membrane and the straight detection of retained fluorescent amyloid
      fibres. We tested 22 chemical compounds from which 11 have already been described
      to affect various prions and other amyloid proteins. Four compounds showed direct
      effects on the aggregation of HET-s. ZnCl seemed to prevent the formation of
      amyloid fibres. Puzzlingly, three members of the group of tannins (tannic acid,
      epigallocatechin and epigallocatechin-gallate) had accelerant properties on
      amyloid aggregation. Resistance of the prion forming domain (PFD) in Proteinase K
      proteolysis assays underlined that tannic acid favours amyloid fibre formation of
      HET-s.

PMID- 16621085
TI  - Conventional gene targeting protocols lead to loss of targeted cells when applied
      to a silent gene locus in primary fibroblasts.
AB  - Gene targeting in livestock fibroblasts has proven difficult to achieve,
      particularly if the target gene is silent. We first tested whether efficient gene
      targeting at the transcriptionally active ovine alpha1(I) procollagen (COL1A1)
      locus required the use of a promoter trap vector. We compared gene targeting
      frequencies at the ovine COL1A1 locus using both a promoter trap and a non
      promoter trap selection strategy. We demonstrated that targeted cells could be
      isolated regardless of whether an enrichment step (promoter trap) was used. Next,
      we used our optimised protocol to target a non-expressed gene, ovine beta-casein.
      We obtained clones that were scored positive by PCR for the targeting event, but
      were negative after cell expansion and Southern analysis. We propose that
      targeted cells were initially generated but that they were at a selective growth
      disadvantage during culture. We suggest modifications to the conventional
      targeting protocol that would prevent such loss of targeted cells.

PMID- 16621086
TI  - Increased production of chymosin by glycosylation.
AB  - Filamentous fungi are well known in the industry as producers of large amounts of
      extracellular proteins. However, production levels of heterologous proteins are
      often disappointing low. In this paper it is shown that increasing glycosylation
      is a powerful strategy for increasing production levels of chymosin in
      filamentous fungi. Two different concepts based on glycosylation were tested.
      First, we improved a poorly used N-glycosylation site within the prochymosin
      molecule. The resulting highly glycosylated chymosin molecule was expressed in
      Aspergillus niger. It was shown that production of the glycosylated protein was
      much more efficient, giving a yield increase of more than 100% compared to
      production of the native chymosin molecule. In an alternative strategy the N
      glycosylation site was located outside of the native chymosin molecule, on a
      linker separating prochymosin from its carrier molecule. Also in this case
      significantly increased production levels were obtained. This strategy might
      offer a powerful tool for increasing production levels of other heterologous
      proteins as well.

PMID- 16621087
TI  - Inhibition of cellulase, xylanase and beta-glucosidase activities by softwood
      lignin preparations.
AB  - The conversion of lignocellulosic biomass to fuel ethanol typically involves a
      disruptive pretreatment process followed by enzyme-catalyzed hydrolysis of the
      cellulose and hemicellulose components to fermentable sugars. Attempts to improve
      process economics include protein engineering of cellulases, xylanases and
      related hydrolases to improve their specific activity or stability. However, it
      is recognized that enzyme performance is reduced during lignocellulose hydrolysis
      by interaction with lignin or lignin-carbohydrate complex (LCC), so the selection
      or engineering of enzymes with reduced lignin interaction offers an alternative
      means of enzyme improvement. This study examines the inhibition of seven
      cellulase preparations, three xylanase preparations and a beta-glucosidase
      preparation by two purified, particulate lignin preparations derived from
      softwood using an organosolv pretreatment process followed by enzymatic
      hydrolysis. The two lignin preparations had similar particle sizes and surface
      areas but differed significantly in other physical properties and in their
      chemical compositions determined by a 2D correlation HSQC NMR technique and
      quantitative 13C NMR spectroscopy. The various cellulases differed by up to 3.5
      fold in their inhibition by lignin, while the xylanases showed less variability
      (< or = 1.7-fold). Of all the enzymes tested, beta-glucosidase was least affected
      by lignin.

PMID- 16621088
TI  - Synthesis of tetrapeptide Bz-RGDS-NH2 by a combination of chemical and enzymatic
      methods.
AB  - The tetrapeptide Bz-Arg-Gly-Asp-Ser-NH(2) (Bz-RGDS-NH(2)) was successfully
      synthesized by a combination of chemical and enzymatic methods in this study.
      Firstly, the precursor tripeptide Gly-Asp-Ser-NH(2) (GDS-NH(2)) was synthesized
      by a novel chemical method in four steps including chloroacetylation of l
      aspartic acid, synthesis of chloroacetyl l-aspartic acid anhydride, the synthesis
      of ClCH(2)COAsp-SerOMe and ammonolysis of ClCH(2)COAsp-SerOMe. Secondly, lipase
      (PPL) was used to catalyze the formation of Bz-RGDS-NH(2) in aqueous water
      miscible organic cosolvent systems using Bz-Arg-OEt as the acyl donor and GDS
      NH(2) as the nucleophile. The optimum conditions were Bz-Arg-OEt 50 mM; GDS-NH(2)
      400 mM; 10 degrees C, 0.1M phosphate buffer, pH 7.5; 60% DMF or 58% DMSO, PPL: 10
      mg ml(-1) with the maximum yields of the tetrapeptide of 73.6% for DMF and 70.4%
      for DMSO, respectively. The secondary hydrolysis of the tetrapeptide product did
      not take place due to the absence of amidase activity of lipase.

PMID- 16621089
TI  - Automated DNA extraction from genetically modified maize using aminosilane
      modified bacterial magnetic particles.
AB  - A novel, automated system, PNE-1080, equipped with eight automated pestle units
      and a spectrophotometer was developed for genomic DNA extraction from maize using
      aminosilane-modified bacterial magnetic particles (BMPs). The use of aminosilane
      modified BMPs allowed highly accurate DNA recovery. The (A(260)-A(320)):(A(280)
      A(320)) ratio of the extracted DNA was 1.9+/-0.1. The DNA quality was
      sufficiently pure for PCR analysis. The PNE-1080 offered rapid assay completion
      (30 min) with high accuracy. Furthermore, the results of real-time PCR confirmed
      that our proposed method permitted the accurate determination of genetically
      modified DNA composition and correlated well with results obtained by
      conventional cetyltrimethylammonium bromide (CTAB)-based methods.

PMID- 16621090
TI  - Analysis of reduction of Geobacillus stearothermophilus spores treated with high
      hydrostatic pressure and mild heat in milk buffer.
AB  - Our unpublished experimental results of fractional factorial experiments showed
      that the significant external factors affecting high pressure processing (HPP)
      inactivation were pressure, temperature and pressure holding time. Based on these
      results, response surface methodology (RSM) was employed in the present work and
      a quadratic equation for HPP inactivation was built. By analyzing the response
      surface plots and their corresponding contour plots as well as solving the
      quadratic equation, the experimental values were shown to be significantly in
      good agreement with predicted values since the adjusted determination coefficient
      (R(Adj)(2)) was 0.9747. The optimum process parameters for six log-cycles
      reduction of Geobacillus stearothermophilus spores were obtained as: temperature,
      86 degrees C; pressure, 625.0 MPa and pressure holding time, 14.0 min. The
      adequacy of the model equation for predicting the optimum response values was
      verified effectively by the validation data.

PMID- 16621091
TI  - Tyrosinase-catalyzed modification of Bombyx mori silk fibroin: grafting of
      chitosan under heterogeneous reaction conditions.
AB  - The capability of mushroom tyrosinase to catalyze the oxidation of tyrosine
      residues of Bombyx mori silk fibroin was studied under heterogeneous reaction
      conditions, by using a series of silk substrates differing in surface and bulk
      morphology and structure, i.e. hydrated and insoluble gels, mechanically
      generated powder and fibre. Tyrosinase was able to oxidize 10-11% of the tyrosine
      residues of silk gels. The yield of the reaction was very low for the powder and
      undetectable for fibres. FT-Raman spectroscopy gave evidence of the oxidation
      reaction. New bands attributable to vibrations of oxidized tyrosine species (o
      quinone) appeared, and the value of the I853/I829 intensity ratio of the tyrosine
      doublet changed following oxidation of tyrosine. The thermal behaviour of SF
      substrates was not affected by enzymatic oxidation. o-Quinones formed by
      tyrosinase onto gels and powder were able to undergo non-enzymatic coupling with
      chitosan. FT-IR and FT-Raman spectroscopy provided clear evidence of the
      formation of silk-chitosan bioconjugates under heterogeneous reaction conditions.
      Chitosan grafting caused a beta-sheet --> random coil conformational transition
      of silk fibroin and significant changes in the thermal behaviour. Chitosan
      grafting did not occur, or occurred at an undetectable level on silk fibres. The
      results reported in this study show the potential of the enzymatically initiated
      protein-polysaccharide grafting for the production of a new range of bio-based,
      environmentally friendly polymers.

PMID- 16621092
TI  - Isolation and cloning of an endo-beta-1,4-mannanase from Pacific abalone Haliotis
      discus hannai.
AB  - An endo-beta-1,4-mannanase was isolated from digestive fluid of Pacific abalone,
      Haliotis discus hannai, by successive chromatographies on TOYPEARL CM-650M,
      hydroxyapatite, and TOYOPEARL HW50F. The abalone mannanase, named HdMan in the
      present paper, showed a molecular mass of approximately 39,000 Da on SDS-PAGE,
      and exhibited high hydrolyic activity on both galactomannan from locust bean gum
      and glucomannan from konjac at an optimal pH and temperature of 7.5 and 45
      degrees C, respectively. HdMan could degrade either beta-1,4-mannan or beta-1,4
      mannooligosaccharides to mannotriose and mannobiose similarly to beta-1,4
      mannanases from Pomacea, Littorina, and Mytilus. In addition, HdMan could
      disperse the fronds of a red alga Porphyra yezoensis into cell masses consisting
      of 10-20 cells that are available for cell engineering of this alga. cDNAs
      encoding HdMan were amplified by polymerase chain reaction from an abalone
      hepatopancreas cDNA library. From the nucleotide sequences of the cDNAs, the
      sequence of 1232 bp in total was determined and the amino-acid sequence of 377
      residues was deduced from the translational region of 1134 bp locating at
      nucleotide positions 15-1148. The N-terminal region of 17 residues except for the
      initiation Met, was regarded as the signal peptide of HdMan because it was absent
      in the HdMan protein and showed high similarity to the consensus sequence for
      signal peptides of eukaryote secretory proteins. Accordingly, mature HdMan was
      considered to consist of 359 residues with the calculated molecular mass of
      39,627.2 Da. HdMan is classified into glycoside hydrolase family 5 (GHF5) on the
      basis of sequence homology to GHF5 enzymes.

PMID- 16621093
TI  - The effect of intracellular ppGpp levels on glutamate and lysine overproduction
      in Escherichia coli.
AB  - Although the enhancement of amino-acid synthesis by guanosine-3',5'
      tetraphosphate (ppGpp) is well known, the effect of intracellular ppGpp levels on
      amino-acid overproduction in Escherichia coli has not been investigated. In this
      study, we demonstrate that overexpression of the relA gene, encoding ppGpp
      synthetase, increases the accumulation of amino acids, such as glutamate and
      lysine, in amino-acid-overproducing strains of E. coli. Elevation of
      intracellular ppGpp levels due to depletion of required amino acids also enhances
      glutamate overproduction. Moreover, the extent of overproduction is highly
      dependent on the intracellular ppGpp level. These results demonstrate that amino
      acid overproduction in E. coli is closely connected to amino-acid auxotrophy via
      the accumulation of ppGpp.

PMID- 16621094
TI  - Constant specific growth rate in fed-batch cultivation of Bordetella pertussis
      using adaptive control.
AB  - Monitoring and control of production processes for biopharmaceuticals have become
      standard requirements to support consistency and quality. In this paper, a
      constant specific growth rate in fed-batch cultivation of Bordetella pertussis is
      achieved by a newly designed specific growth rate controller. The performance of
      standard control methods is limited because of the time-varying characteristics
      due to the exponentially increasing biomass and volume. To cope with the changing
      dynamics, a stable model reference adaptive controller is designed which adapts
      the controller settings as volume and biomass increase. An important asset of the
      design is that dissolved oxygen is the only required online measurement. An
      original design without considering the dissolved oxygen dynamics resulted
      experimentally in oscillatory behaviour. Hence, in contrast to common believes,
      it is essential to include dissolved oxygen dynamics. The robustness of this
      novel design was tested in simulation. The validity of the design was confirmed
      by laboratory experiments for small-scale production of B. pertussis. The
      controller was able to regulate the specific growth rate at the desired set
      point, even during a long fed-batch cultivation time with exponentially
      increasing demands for substrates and oxygen.

PMID- 16621095
TI  - K562 cell growth activity and metabolism characteristics in APA microencapsulated
      culture and modeling study.
AB  - Cell microencapsulation is likely to play a major role in cell and
      transplantation therapies in the next decade. The microcapsules provide a special
      microenvironment in which cells always have different behaviors compared with
      free non-encapsulated culture. In this work, the behaviors of K562 leukemia cells
      were studied once entrapped in solid and liquefied APA microcapsules as well as
      in free non-encapsulated culture. Glucose pulse culture was employed to
      characterize the growth and metabolism of microencapsulated K562 cells. And
      mathematical modeling was presented to develop a basis for the deeper
      understanding of cells responses to different culture environments. Based on the
      results of experiments and modeling, it was found that cells presented a better
      growing pattern and maintain the activity at a higher level for extending time.
      The concentration of lactate was higher in solid microcapsules culture than that
      of liquefied microcapsules culture, but the cell number was lower. And the
      lactate yield coefficients (lactate/glucose) were 0.8129, 0.6978 and 0.601 for
      free non-encapsulated, solid microcapsules and liquefied microcapsules culture,
      respectively. An increase of glucose concentration led a decrease of cell
      activity, The glucose consumption ratio were 99.9%, 86.8%, 49.4% and 28.6% with
      the decrease in its concentration from 2 to 4, 6, 10 g/L, however, the lactate
      yield coefficient were 0.7184, 0.6654, 0.8239 and 0.9693, respectively.

PMID- 16621096
TI  - Molecular cloning of carboxylesterase gene and biochemical characterization of
      encoded protein from Bacillus subtilis (RRL BB1).
AB  - An isolated strain of Bacillus subtilis identified by 16S rDNA sequence analysis
      produces an enantioselective ester hydrolase. Whole cells of B. subtilis (RRL
      BB1) and enzyme derived from it was capable of enantioselective hydrolysis of
      several racemates including drug intermediates with moderate to high
      enantioselectivity as already reported by us. In this communication, we describe
      cloning of the gene encoding the enantioselective esterase designated as estBB1.
      The primary structure of the enzyme determined from the nucleotide sequence
      indicated that esterase estBB1 has Mw approximately 52kDa and pI approximately
      5.2 and belongs to the family of type B carboxylesterases with 50-60% similarity
      at amino acid level. Alignment studies of sequences of the estBB1 and Pnb
      esterase 56C8 from B. subtilis showed that estBB1 has an alpha/beta hydrolase
      fold with catalytic triad formed by Ser190, Glu305 and His394 at active site and
      Ser190 is located in the conserved motif -G-X-S-X-G-.

PMID- 16621097
TI  - Cloning, expression and identification of ferritin from Chinese shrimp,
      Fenneropenaeus chinensis.
AB  - Ferritin, the iron storage protein, plays a key role in iron metabolism. A cDNA
      encoding ferritin (FcFer) was cloned from hepatopancreas of Chinese shrimp,
      Fenneropenaeus chinensis. The predicted protein contains 170 amino acid residues
      with a predicted molecular weight (MW) about 19, 422.89 Da and theoretical
      isoelectric point (PI) of 4.73. Amino acid alignment of FcFer revealed 97%
      homology with Litopenaeus vannamei ferritin. Results of the RT-PCR showed that
      the expression of FcFer mRNA was up-regulated after shrimp was challenged with
      either white spot syndrome virus (WSSV) or heavy metal ions (Zn2+ and Cu2+) in
      the laboratory. A fusion protein containing FcFer was produced and the purified
      recombinant protein exhibited similar function of iron uptake in vitro. The
      result of in-gel digestion and identification using LC-ESI-MS showed that two
      peptide fragments (-DDVALPGFAK- and -LLEDEYLEEQVDSIKK-) of the recombinant
      protein were identical to the corresponding sequence of L. vannamei ferritin. The
      recombinant FcFer protein will be proved useful for study on the structure and
      function of ferritin in F. chinensis.

PMID- 16621099
TI  - Specific binding of heat shock protein 70 with HN-protein inhibits the HN-protein
      assembly in Sendai virus-infected Vero cells.
AB  - The production of hemagglutinating virus of Japan (HVJ; Sendai virus) was
      inhibited at 41 degrees C, whereas it was normal at 37 degrees C. In the infected
      Vero cells, viral specific proteins were synthesized even at 41 degrees C, but
      the synthesized HN protein was not integrated into the cell membrane, resulting
      in the inhibition of viral production. To investigate the relationship of HSP70
      to the inhibition of HN-protein integration, the expression of HSP70 was induced
      by prostaglandin A1 (PGA1) at 37 degrees C, and the influence on viral infection
      was examined. The induction of HSP70 at 37 degrees C inhibited the viral
      production. Viral proteins were also synthesized, even in the presence of PGA1.
      However, HN protein was not as present on the cell membrane following PGA1
      treatment as it was at 41 degrees C, whereas F protein was detected. An
      immunoprecipitation assay showed that HSP70 was coprecipitated with HN protein,
      but not with F protein. The results suggested that the specific interaction of
      HSP70 with HN protein prevented the protein from integrating into the cell
      membrane. In addition, the abnormal virus-like particles, of which HN protein and
      nucleocapsid were ablated, were released in the culture medium at 41 degrees C,
      although the size was smaller than the normal viral virions. The results suggest
      that HN protein is necessary for viral morphogenesis.

PMID- 16621100
TI  - Microglial cells initiate vigorous yet non-protective immune responses during HSV
      1 brain infection.
AB  - Central nervous system (CNS) infection with herpes simplex virus (HSV)-1 triggers
      neuroinflammatory responses leading to peripheral immune cell infiltration into
      the brain. Previous in vitro studies from our laboratory, using primary human
      brain cells, implicated microglia as the cellular source of infection-induced
      chemokines, such as CXC ligand 10 (CXCL10) and CC ligand 2 (CCL2). Here, we
      evaluated the role of microglial cells in HSV-induced neuroimmune responses using
      an in vivo murine model of herpes encephalitis. Data obtained during this study
      demonstrated robust levels of CXCL10, CCL2 and CXCL9 detectable in the brains of
      infected BALB/c mice between 5 and 8 days post-infection (p.i.). Microglial cells
      were identified as a source of this HSV-induced chemokine production. Additional
      experiments established that induction of these immune mediators preceded the
      presence of CD3, CD4, CD8, and CD45 mRNA in the brain, and immunohistochemical
      analysis confirmed the presence of infiltrating CD3(+) cells. Further analysis
      suggested that microglia-derived chemokines drive peripheral immune cell
      chemotaxis, as antibodies to CXCL10 and CCL2 blocked the migration of murine
      splenocytes toward HSV-infected microglia by approximately 59.3+/-4.1% and 17.5+/
      1.4%, respectively. Taken together, these results demonstrate that a vigorous
      microglia-driven cascade of pro-inflammatory immune responses is not sufficient
      to protect susceptible mice from HSV-1 brain infection.

PMID- 16621101
TI  - Caspase 3 activation during herpes simplex virus 1 infection.
AB  - During herpes simplex virus 1 (HSV-1) infection, apoptosis is initiated by
      immediate early gene transcription and is later modulated by proteins synthesized
      in infected cells. We have previously shown that procaspase 3 levels are reduced
      during HSV-1 replication. We now demonstrate that a replication-defective HSV-1
      recombinant virus which is incapable of packaging viral DNA into capsids
      activated caspase 3 but retained the ability to prevent the apoptotic process
      from killing the infected cells. This implies that HSV-1-dependent apoptosis is
      not merely a response to abortive infection. Maximum accumulation of the active
      form of caspase 3 accompanied complete HSV-1-dependent apoptosis. Additionally,
      caspase 7 was found to be activated during HSV-1-dependent apoptosis. Infected
      MCF-7 cells which ectopically express caspase 3 underwent more efficient
      apoptosis than their caspase 3-null parental counterparts, confirming that
      caspase 3 contributes to HSV-1-dependent apoptosis. However, caspase 3
      reconstitution did not make the MCF-7 cells as sensitive as HEp-2 cells to HSV-1
      dependent apoptosis, suggesting that other cellular factors may be involved in
      conferring resistance to this process. These results indicate that caspase 3
      activation is a consequence of HSV-1 infection and have important implications in
      our understanding of the interactions of the virus with host cells.

PMID- 16621102
TI  - Asian prunus viruses: New related members of the family Flexiviridae in Prunus
      germplasm of Asian origin.
AB  - Serological reactivity to Plum pox virus (PPV) antisera has been described in
      several Prunus sources of Asian origin that are free of PPV infection. Using
      polyvalent or specific PCR assays, the presence of three closely related agents
      in two of these sources, Prunus mume cv. Bungo and P. persica cv. Ku Chu'a Hung,
      was demonstrated. Similarities in genome organization and sequence comparisons
      indicate that these agents should be regarded as members of the genus Foveavirus,
      their only singular trait being a very large (>800 nt) 3' non-coding region
      (NCR), as compared to the ca. 130-180 nt 3' NCR observed in other Foveaviruses.
      The three agents are very divergent from known Foveaviruses but are also
      significantly removed one from the others, with overall nucleotide sequence
      identity levels in the sequenced region of ca. 74-76% and of only 60.8-67.5% in
      their complete CP gene (61.9-71.3% amino acid sequence identity). Given the
      species discrimination criteria in the family Flexiviridae, these three agents
      should be regarded as three related yet distinct new viruses belonging to the
      Foveavirus genus, for which the names Asian prunus virus 1, 2 and 3 are proposed.
      Evidence is provided for the presence of variants of these new viruses in other
      Prunus germplasm of Asian origin.

PMID- 16621103
TI  - Venezuelan equine encephalitis virus complex-specific monoclonal antibody
      provides broad protection, in murine models, against airborne challenge with
      viruses from serogroups I, II and III.
AB  - The alphavirus Venezuelan equine encephalitis virus (VEEV) is highly infectious
      by the airborne route. It is a hazard to laboratory workers, has been developed
      as a biological weapon and is a potential bioterrorist agent. A suitable vaccine
      appears in an advanced stage of development but there remains a need for
      antiviral drugs, effective in prophylaxis of disease prior to or a short time
      after exposure to airborne virus. Using a murine model to study monoclonal
      antibody (MAB) a VEEV complex-specific, glycoprotein E2-binding MAB was
      identified, able to protect against disease induced by exposure to aerosolised
      VEEV from serogroups I, II and IIIA (mouse-virulent strains). There was no
      synergy in protection between anti-E1 and anti-E2 MAB. Assays of MAB virus
      neutralising activity in a homologous (mouse fibroblast) cell line suggested that
      neutralisation played a significant role in protection in addition to the
      previously reported mechanism of Fc receptor-binding [Mathews et al., 1985. J.
      Virol. 55, 594-600]. Development of an analogous human MAB with identical VEEV
      epitope specificity may be informed and monitored by reference to these
      properties.

PMID- 16621098
TI  - Risk of HIV-1 transmission by breastfeeding among mothers infected with
      recombinant and non-recombinant HIV-1 genotypes.
AB  - BACKGROUND: Viral genotype and intersubtype recombination may influence the rate
      and/or timing of mother-to-child HIV-1 transmission. METHODS: We determined the
      HIV-1 subtype of the C2-C5 env and 5'LTR regions from milk and blood samples of
      61 Tanzanian mothers who transmitted the virus through breastfeeding and their
      HIV-1 positive non-transmitting controls. Cases and controls were matched on
      infant's age at sample collection. All mothers resided in Dar es Salaam,
      Tanzania. RESULTS: Most infections among cases were due to recombinant viruses
      (41.0%), followed by HIV-1 subtype A (26.2%), subtype D (19.7%), and subtype C
      (13.1%). In multivariate analysis including maternal CD4+ cell counts, HIV
      disease stage, and proviral load in breast milk, the odds of breast milk
      transmission were 7.2 times higher if the mother carried an intersubtype
      recombinant genome in comparison to a subtype C virus (p=0.02). Viruses with
      recombinant LTRs were 4.9 times more likely to be transmitted through
      breastfeeding than viruses with non-recombinant LTRs of subtype A, C or D
      combined (p=0.01). CONCLUSIONS: This suggested that intersubtype recombinant
      genomes, and especially recombination within the LTR, might render HIV-1 more fit
      for transmission via breast milk in comparison with non-recombinant subtypes A,
      C, and D.

PMID- 16621104
TI  - Induction of classical and nonclassical MHC-I on mouse brain astrocytes by
      Japanese encephalitis virus.
AB  - Infection with Flaviviruses upregulates the cell surface expression of MHC-I, MHC
      II, ICAM-1 (CD54), VCAM-1 (CD106) and TAP proteins. Although all these studies
      have been confirmed using West Nile virus and other Flaviviruses, there are few
      reports that have examined the effects of Japanese encephalitis virus (JEV)
      infection directly on nonclassical and classical MHC expression in astrocytes. We
      show in this report that JEV infection of mouse brain astrocytes results in
      induction of the nonclassical MHC Class Ib genes, H-2T23, H-2Q4 and H-2T10 in
      addition to MHC-I, Type I (alpha/beta) IFNs, TAP-1, TAP-2, Tapasin, LMP-2, LMP-7
      and LMP-10 but not IFNgamma, CD80, CD86 and MHC-II genes. The increased cell
      surface expression of these antigens as well as induction of the genes mentioned
      above as measured by RT-PCR suggests that JEV infection may lead to the induction
      of classical MHC Class Ia as well as nonclassical MHC Class Ib molecules.

PMID- 16621105
TI  - Incidence of type-2 diabetes mellitus in a large population of Japanese male
      white-collar workers.
AB  - Since occupation, a major socio-economic factor, may be a risk factor for type-2
      diabetes mellitus (DM), we compared DM incidence among four groups of white
      collar workers in a follow-up study in 13,547 Japanese men. The subjects aged 30
      59 years and free from DM at baseline consisted of: (a) 3725 clerical, (b) 5575
      technical/professional, (c) 3474 manager/administrative and (d) 774 sales
      workers. Incident DM was identified by 'fasting serum glucose >or=7.00 mmol/l' or
      'under medical treatment for DM'. Hazard ratio (HR) and 95% confidence interval
      (CI) for incident DM were estimated using clerical workers as the reference group
      (HR=1.00). Baseline age, body mass index (BMI), drinking, smoking, exercise and
      education were computed as confounders. During mean follow-up periods of 7.4
      years, 176 clerical, 264 technical/professional, 195 manager/administrative and
      49 sales workers developed DM (6.0, 6.1, 8.8 and 9.4 per 1000 person-years,
      respectively). Sales workers aged 40-49 and 50-59 years had increased
      multivariate-adjusted HRs (95% CIs) of 1.55 (1.02, 2.35) and 2.01 (0.98, 4.10),
      respectively. Manager/administrative workers aged 50-59 years had an increased
      crude HR (95% CI) of 1.64 (1.02, 2.63), but the significance disappeared after
      BMI-adjustment (HR (95% CI: 1.46 (0.91, 2.35)). Technical/professional workers
      had no significant HR in any model. In conclusion, sales workers in Japan aged
      >or=40 years may have increased risk for DM (+55 to +100%) independent of BMI,
      lifestyles and education, and manager/administrative workers aged >or=50 years
      may have increased risk (about +65%) due to their large BMI.

PMID- 16621106
TI  - Pulsatile insulin secretion in elderly patients with diabetes.
AB  - Insulin pulsation is impaired in type 2 diabetes. GLP-1 increases pulsatile
      insulin secretion in these patients. We conducted these studies with the
      hypothesis that GLP-1 would enhance pulsatile insulin secretion and alter glucose
      metabolism in elderly patients with type 2 diabetes. Experiments were conducted
      in nine patients (age: 72+/-5 years; BMI: 27+/-3kg/m(2); diabetes duration: 7+/-3
      years; HbA(1c): 6.6+/-0.9%). Subjects underwent three glucose clamp studies. The
      first was a euglycemic clamp to determine individual insulin clearance. In the
      second, GLP-1 was infused from 0-240min (0.75pM/kg/min) and glucose was
      maintained at fasting levels. The third was similar except that octreotide
      (30ng/kg/min) was infused with GLP-1 to suppress pulsatile insulin. Insulin and
      glucose were given to match levels during the second study. 3-(3)H-glucose was
      infused to allow calculation of hepatic glucose production and glucose disposal
      rates. There was no significant difference in measurements of pulsatile insulin
      secretion or hepatic glucose production and glucose disposal rates between the
      studies. Because there was no difference in pulsatile insulin between
      experiments, we could not test the effect of pulsatile insulin on glucose
      metabolism. Further studies are required to determine the impact of insulin
      pulses on glucose metabolism.

PMID- 16621107
TI  - Association of APOE (Hha1) and ACE (I/D) gene polymorphisms with type 2 diabetes
      mellitus in North West India.
AB  - Familial and epidemiological studies have shown that genetic factors play a role
      in the development and progression of type 2 diabetes mellitus (T2DM). Asian
      Indians have shown an increasing prevalence of T2DM. Apolipoprotein E (APOE) and
      Angiotensin-1 converting enzyme (ACE) I/D polymorphisms have been associated with
      T2DM. This study examined the association of APOE and ACE genes with T2DM
      patients of Punjab, India. APOE (HhaI) and ACE (I/D) genotypes analysed by
      polymerase chain reaction were available from 90 patients and 97 random healthy
      controls. All loci and populations are in Hardy-Weinberg equilibrium. There is no
      significant association of APOE vis-a-vis T2DM, however APOE*4 allele frequency
      is low in diabetics (3.9% and 8.8%). DD genotype and *D allele of ACE are
      associated with T2DM (OR=1.90, p<0.05, and OR=1.58, p<0.05, respectively).
      Recessive and multiplicative mode of inheritance for *D allele provided the
      strongest support for the association. Height, weight and BMI did not reveal any
      significant association with APO or ACE. DD-33 and ID-23 combinations (ACE-APOE)
      showed higher odds of 2.01 and 2.14, respectively. ACE but not APOE polymorphism
      is positively associated with T2DM in Indian population, however, the synergistic
      effects of DD-33 and ID-23 are also evident.

PMID- 16621108
TI  - Arterial wall thickening and stiffening in children and adolescents with type 1
      diabetes.
AB  - OBJECTIVE: We evaluated structural and functional characteristics of the common
      carotid artery (CCA), a marker of early carotid atherosclerosis, and investigated
      their relation to metabolic and anthropometric parameters in children and
      adolescents with type 1 diabetes. MATERIALS AND METHODS: Non-invasive
      ultrasonographic measurements were made in 45 type 1 diabetic patients and 33
      controls. Age, sex, and body mass index were matched between patients and
      controls. We investigated intima-media thickness (IMT), compliance,
      distensibility, diastolic wall stress (DWS) and incremental elastic modulus (IEM)
      of the CCA. Metabolic and anthropometric parameters such as serum lipids, plasma
      glycated haemoglobin, body mass index, waist-hip ratio and blood pressure were
      assessed. RESULTS: The diabetic patients had significantly higher CCA-IMT than
      the controls (0.48+/-0.06mm versus 0.33+/-0.07mm; p<0.001). The diabetic children
      had significantly higher values than the controls for DWS (1.18+/-0.29mmHgx10(2)
      versus 0.81+/-0.25mmHgx10(2); p<0.001) and for IEM (1.26+/-0.57mmHgx10(3) versus
      0.77+/-0.28mmHgx10(3); p<0.001). The difference was not significant between
      patients and controls for arterial compliance and for distensibility (p>0.05). In
      a multivariate regression model for all subjects, diabetic state was the best
      predictor of IMT (p<0.001), DWS (p<0.001) and IEM (p=0.001). CONCLUSION: Our
      results suggested that children and adolescent patients with type 1 diabetes are
      associated with early impairment of CCA structure and function and that diabetic
      state may be the main risk factor for CCA wall stiffening and thickening, which
      are of considerable concern as possible early events in the genesis of atheroma.

PMID- 16621109
TI  - Childhood type 1 diabetes mellitus in Newfoundland and Labrador, Canada.
AB  - The aim of this study was to calculate incidence and hospitalization rates of
      childhood type 1 diabetes mellitus (T1DM) in Newfoundland and Labrador, and to
      assess hospitalization trends and associated factors. Data for all patients aged
      0-19 years with a diagnosis of T1DM was obtained from the clinical database
      management system (CDMS) for a 7-year period between April 1, 1995 and March 31,
      2002. Incidence was calculated for the 0-7 years age group. A total of 894 T1DM
      hospital separations among children aged 0-19 years were identified, representing
      a hospitalization rate of 88.6 per 100,000 person-years (P-Y). The CDMS
      identified 518 incidences of hospitalization (51.2 per 100,000 P-Y). The overall
      hospitalization rate increased over the study period (P((2))=0.065).
      Hospitalization rates for males and females were 77.3 and 100.2 per 100,000 P-Y,
      respectively (P((2))=0.00011). Of the 894 hospitalization separations, 216
      hospitalizations were for diabetic ketoacidosis (DKA) (21.4 per 100,000 P-Y).
      Female gender and older age were found to be predictive factors of DKA. The
      incidence rate of T1DM among children aged 0-7 years was 19.0 per 100,000 P-Y.
      Newfoundland and Labrador has one of the highest incidence rates of T1DM in the
      world. Hospitalization rates for DKA and non-DKA increased slightly over the
      study period. Age and sex patterns suggest that DKA is a particular challenge
      among adolescent girls. Preventive strategies are needed, particularly in areas
      of the province with the highest rates.

PMID- 16621110
TI  - Insulin resistance in Brazilian adolescent girls: association with overweight and
      metabolic disorders.
AB  - We assessed the association between insulin resistance, overweight and metabolic
      disorders in a probabilistic sample of 388, 12-19-year-old girls from public
      schools in Niteroi, Rio de Janeiro State, Brazil. Insulin resistance was
      determined using Homeostatic Model Assessment-Insulin Resistance (HOMA-IR).
      Overweight and obesity were defined by the sex- and age-specific body mass index
      cut-offs recommended by the International Obesity Task Force. Metabolic syndrome
      (MS) was identified by the presence of at least three of the following factors:
      fasting glucose >or=100mg/dL, triglycerides >130 mg/dL, LDL-C >or=110 mg/dL, HDL
      C <35 mg/dL and overweight. The combined prevalence of obesity (2.9%) and
      overweight was 14.2%. The average HOMA-IR level was 2.24 (95% confidence
      interval=1.40-3.10) in the overweight group and 1.91 (95% CI=1.32-2.50) in the
      non-overweight one, and MS prevalence was 20 times higher in the first group
      (21.4 and 0.1%). MS prevalence in the overweight group was 6.3 times higher in
      adolescents above the 66th percentile of HOMA-IR (55.9%) than those under the
      33rd percentile (8.9%). Brazilian overweight girls with higher insulin resistance
      had high risk of developing MS. Therefore, prevention should occur at an early
      age to impair the evolution of this process.

PMID- 16621111
TI  - Effect of glucagon-like peptide-1 (7-37) on beta-cell function after islet
      transplantation in type 1 diabetes.
AB  - Islet transplantation can improve glycemic control in patients with type 1
      diabetes and reduce or eliminate the need for insulin. Glucagon-like peptide-1
      (GLP-1) is an intestinal insulinotropic hormone that augments glucose induced
      insulin secretion, and has a trophic effect on beta-cells. We evaluated the
      effect of GLP-1 on insulin secretion after islet transplantation. Patients
      underwent hyperglycemic glucose clamp studies 1 month after their last
      transplant. GLP-1 was infused during the second hour of the hyperglycemic clamp.
      Results were compared to normal control subjects and patients with type 2
      diabetes who underwent an identical hyperglycemic clamp. First phase insulin
      release was absent in patients, while second phase insulin was not significantly
      reduced (control: 118+/-29 pM; type 2 diabetes: 68+/-20 pM; transplant: 99+/-18
      pM, p=ns for all). GLP-1 had a significant incretin effect on transplanted islets
      but the response was less than controls (control: 2108+/-344 pM; type 2 diabetes:
      929+/-331 pM; transplant: 329+/-112 pM, p<0.0001 control versus transplant).
      Islet transplant patients had no evidence of resistance to insulin mediated
      glucose disposal. We conclude that transplanted islets retain the ability to
      respond to GLP-1.

PMID- 16621112
TI  - Predictors of incident diabetes, metabolic syndrome in middle-aged adults: a 10
      year follow-up study from Kinmen, Taiwan.
AB  - AIMS/HYPOTHESIS: The aim of this prospective study was to assess a population
      based cohort for the predictors of incident diabetes and metabolic syndrome,
      which is most likely to lead to cardiovascular disease. METHODS: We compared the
      baseline individual components of metabolic syndrome, adopted from the NCEP ATP
      III for Asians, in 3629 subjects who developed diabetes, metabolic syndrome, or
      diabetes and metabolic syndrome to those who remained free of diabetes and
      metabolic syndrome for 10 years. RESULTS: The incidence rate of diabetes was 7.8%
      (9.8% in men and 6.3% in women, respectively), and metabolic syndrome was 24.2%
      (23.4% in men and 24.7% women, respectively). Eighty-five men and 99 women
      developed diabetes and metabolic syndrome, which yielded incidence rates of 5.7%
      in men and 4.7% in women. After adjustment for related covariable factors, each
      component of metabolic syndrome in women, higher triglyceride and greater waist
      circumference in men, independently predicted future incident diabetes and
      metabolic syndrome as compared with those who remained free of diabetes and
      metabolic syndrome. CONCLUSIONS/INTERPRETATION: These findings suggest that
      several components of metabolic syndrome independently precede the development of
      diabetes and metabolic syndrome. Further intervention studies are required to
      demonstrate the benefits of intervention with all aspects in decreasing the
      incidence of diabetes and metabolic syndrome in the general population.

PMID- 16621113
TI  - Telecare in a structured therapeutic education programme addressed to patients
      with type 1 diabetes and poor metabolic control.
AB  - OBJECTIVE: To assess the effects of telecare on the results of intensive follow
      up in T1D patients with poor metabolic control. METHODS: After initial
      evaluation, 40 T1D were randomised to either a Telecare (TG) or Conventional
      Group (CG). Patients had an intensive 6-month follow-up and helped to make
      decisions concerning treatment self-management. The TG had 12 appointments: 9
      telematic with the GlucoBeep system+3 ambulatory. The CG had 12 outpatient
      appointments. At 0, 6 (end of study) and 12 months, metabolic control, self
      management and quality of life were evaluated. Cost analysis was made at study
      end. RESULTS: Thirty patients completed the study (16 TG, 14 CG). Intention to
      treat analysis included 19 TG and 16 CG. Improvement in HbA(1c) was similar in
      both groups TG: 8.4+/-1.2%; 7.5+/-1.4%; 7.6+/-0.9%, p=0.008; CG: 8.9+/-1.3%;
      7.7+/-0.9%; 7.6+/-0.7%, p=0.001; with a decrease in hypoglycaemic events and
      improvement in self-management and quality of life. Patient costs were lower in
      the TG versus CG in appointment length (0.25h versus 0.5h). However, 30% of the
      diabetes team and patient appointments were longer than expected due to technical
      difficulties: (0.25h versus 1h). CONCLUSIONS: Intensive telematic follow-up
      achieves similar results to those of intensive face-to-face follow-up with lower
      patient costs. However, communication technology must be improved.

PMID- 16621114
TI  - Microalbuminuria presents the same vascular risk as overt CVD in type 2 diabetes.
AB  - OBJECTIVES: We attempted to assess whether microalbuminuria conferred the same
      cardiovascular risk as overt CVD in type 2 diabetic patients. MATERIAL AND
      METHODS: A prospective cohort study including 436 type 2 diabetic patients
      (64.8+/-9.2 years old) without proteinuria, with follow-up until any
      cardiovascular event occurred, was performed. Patients were classified into four
      groups: group 0, non baseline CVD and normoalbuminuria; group 1, non baseline CVD
      and microalbuminuria; group 2, baseline CVD and normoalbuminuria; group 3,
      baseline CVD and microalbuminuria. Cox's multivariate regression models were used
      to assess the risk ratio (RR) associated with each variable. RESULTS: The median
      follow-up time was 7.6 years. Incidence rates of cardiovascular events per 1000
      patient-years increased from groups 0 to 3 (23.8, 63.4, 74.1, 85.6; p<0.0001).
      Multivariate RR for incident CVD in groups 1, 2 and 3 in relation to group 0 were
      2.8 (95% confidence interval (CI) 1.7-4.6; p<0.0001), 2.7 (95% CI 1.6-4.6;
      p<0.0001) and 2.9 (95% CI 1.6-5.4; p=0.001), respectively. No significant
      differences were seen between groups 1 and 2. CONCLUSIONS: We suggest that
      patients with microalbuminuria are at very high vascular risk and should share
      the same objectives of a vascular risk-factor control as patients with overt CVD.

PMID- 16621115
TI  - Prognostic significance of the white coat hypertension in patients with type 1
      diabetes mellitus.
AB  - Despite the high prevalence of white coat hypertension (WCH) in diabetes mellitus
      and the evidence that hypertension is a clear risk factor for the development of
      microalbuminuria (MA) in these patients, there is no information on the long-term
      prognostic significance of this condition in the diabetic population. We studied
      the evolution of 40 patients with type 1 diabetes mellitus (Type 1 DM). Twenty
      patients with WCH (office blood pressure> or =140/90mmHg associated with mean
      daytime blood pressure<135/85mmHg) classified as the WCH group and 20 patients
      with type 1 DM with a similar age and disease evolution, but who were
      normotensive, (office blood pressure<140/90mmHg associated with mean daytime
      blood pressure<135/85mmHg) classified as the normotensive control group. After 5
      years of follow-up, MA appeared in four subjects and sustained hypertension in
      another, with a total of 31% of events in the WCH group, with none in the
      normotensive group. Kaplan-Meier analysis showed that the relative risk of
      developing these hypertensive events was 25% higher in the WCH group. At
      baseline, the night time systolic and diastolic blood pressure levels were
      significantly higher in patients who further developed MA and sustained
      hypertension. The findings in this study highlight the clinical importance of
      careful follow-up of type 1 diabetic patients with WCH.

PMID- 16621116
TI  - Comparison of breakfast and bedtime administration of insulin glargine in
      children and adolescents with Type 1 diabetes.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of administration
      time of insulin glargine (IG) on glycemic control in children and adolescents
      with Type 1 diabetes. MATERIALS AND METHODS: A total of 31 children and
      adolescents (15 F and 16 M) with Type 1 diabetes on intensive therapy (bedtime
      NPH and premeal insulin aspart) were randomized to receive once-daily IG either
      at breakfast (breakfast group, n=15) or bedtime (bedtime group, n=16) while
      continuing insulin aspart premeals for 6 months. Blood glucose levels were
      measured fasting, preprandially and bedtime. Total daily insulin dose (TDD), body
      mass index (BMI), glycosylated hemoglobin (HbA(1c)), and frequency of
      hypoglycemia in the preceding 3 months were assessed at recruitment, third month
      and sixth month. RESULTS: The dose of IG, TDD, and fasting blood glucose levels
      were similar in both groups during the study period. The only significant
      difference in blood glucose levels between breakfast and bedtime groups was found
      for dinnertime at 6 months (135+/-26mg/dl versus 161+/-33mg/dl, respectively,
      p=0.035). In the breakfast group, the mean HbA(1c) level was significantly lower
      than that of baseline at month 6 (9.4+/-2.5% versus 8.0+/-0.9%, respectively,
      p=0.022), whereas there was no significant change in the bedtime group (9.2+/
      2.1% versus 8.9+/-2.2%, respectively). The frequency of hypoglycemia was lower
      with IG than NPH (2.7+/-2.8/6 months versus 6.4+/-6.7/6 months, respectively,
      p=0.008). CONCLUSIONS: Once-daily IG at breakfast in children and adolescents
      with Type 1 diabetes on intensive therapy is more efficacious than bedtime
      administration to improve metabolic control. Also, the number of hypoglycaemic
      events decreased with both breakfast and bedtime administrations of IG.

PMID- 16621117
TI  - The status of diabetes control and antidiabetic drug therapy in Japan--a cross
      sectional survey of 17,000 patients with diabetes mellitus (JDDM 1).
AB  - The number of diabetic patients has been increasing in Japan and consequently
      diabetic complications are the most important target to be prevented through
      improving glycemic control. In order to describe the glycemic control status and
      treatment of diabetic patients by specialists in Japan over three years, from
      2000 to 2002, we examined HbA1c, other laboratory data and the modality of drug
      therapy in the study population, 8170 in 2000, 11,831 in 2001, and 16,934 in
      2002. Patients were registered at clinics and hospitals that were members of the
      Japan Diabetes Clinical Data Management Study Group (JDDM). HbA1c levels, other
      laboratory data, and details of drug therapy were collected and analyzed using
      SPSS and MS Access. The mean HbA1c levels were essentially unchanged during the
      study periods, ranging from 7.9% to 7.8%, and from 7.1% to 7.0%, in type 1 and
      type 2 diabetic patients, respectively. In type 2 diabetes, the frequency of oral
      hypoglycemic agents (OHA) use increased from 44.9% to 51.4%, while the use of
      diet-only therapy decreased from 29.9% to 25.4% over the study period. Although
      the systolic blood pressure was slightly above target, the mean blood pressure
      and the mean lipid profile were mostly within the treatment goals set by the
      Japan Diabetes Society. This first report from a large scale study of the daily
      management of diabetes in Japan revealed that the average HbA1c level was
      superior to most of the results reported from other countries. Nonetheless, 66%
      of the patients still had HbA1c levels and half of the patients had other
      laboratory parameters including blood pressure and lipid profile that were
      greater than those recommended by the Japan Diabetes Society. The nature of
      diabetes drug therapy in Japan has gradually changed as new drugs have appeared
      in the market.

PMID- 16621118
TI  - The influence of glucose self-monitoring on glycaemic control in patients with
      diabetes mellitus in Sudan.
AB  - OBJECTIVE: To investigate the influence of self-monitoring of glucose on the
      glycaemic control in Sudanese diabetic subjects. SUBJECTS AND METHODS: A group of
      193 consecutive type 2 and type 1 diabetic subjects (95 men, 98 women) were
      studied. In 104 subjects with type 2 diabetes fasting blood glucose was measured
      using a glucose meter and blood was obtained for serum glucose measurement in the
      laboratory. In the remaining 89 diabetic subjects random blood glucose was
      measured using the same glucose meter and a whole blood sample was drawn for
      laboratory assessment of HbA1c. Data on self-monitoring and other clinical and
      personal characteristics were recorded. RESULTS: More than 75% of either type 1
      and type 2 diabetic patients never self-monitored blood or urine glucose. In type
      2 diabetic subjects self-monitoring of blood or urine glucose was not related to
      glycaemic control. In type 1 diabetic subjects, however, self-monitoring of blood
      glucose was significantly associated with better glycaemic control, as assessed
      by HbA1c (P=0.02) and blood glucose at clinic visits (P< or =0.0001), and similar
      associations were found for urine glucose self-monitoring (P=0.04 and 0.02)
      respectively. Neither glycaemic control nor glucose self-monitoring was
      associated with education level. CONCLUSIONS: Self-monitoring of blood glucose
      was not found to be associated to better glycaemic control in Sudanese subjects
      with type 2 diabetes. In contrast, self-monitoring of both blood and urine
      glucose was significantly associated with glycaemic control in subjects with type
      1 diabetes. Self-monitoring of urine glucose could be useful where measurement of
      blood glucose is not available or affordable.

PMID- 16621119
TI  - Health care funding reforms in Croatia: a case of mistaken priorities.
AB  - This study provides an overview of funding mechanisms in Croatian health care and
      analyses them in terms of sustainability, efficiency and equity. The study
      presents an in depth investigation of problems facing funding health care in
      Croatia: high expenditure, inadequate financial resources, continuous deficits of
      the state insurance fund, lack of transparency in funding, an aging population,
      etc. Furthermore, the study provides a critical overview of reforms that have
      been implemented to counter those issues from 1990 to 2002. The study argues that
      the implemented reforms over relied on shifting health expenditure from public to
      private sources in addressing financial deficits in the system. The study argues
      that, instead, the reforms should have focused more on curbing rising expenditure
      in health care providers. Emphasis has been put on the extent to which the
      reforms affected the conceptual-social foundations of the system. Finally, the
      paper provides recommendations for policy makers in Croatia and presents an
      overview of Croatian experiences that might be of interest to researchers and
      policy makers internationally.

PMID- 16621120
TI  - Knowledge into action? understanding ideological barriers to addressing health
      inequalities at the local level.
AB  - The objective of this study was to explore the presence of ideological barriers
      to addressing local health inequalities in Hamilton, Ontario, Canada. A survey of
      active citizens revealed low levels of awareness of the social determinants of
      health (SDOH) framework, and some incongruence between understanding and
      attitudes towards the SDOH. Support for addressing health inequalities was
      associated with awareness of the SDOH framework, liberal value-systems, and a
      cluster of socio-demographic characteristics. Liberal leaning participants were
      also more politically active than their conservative counterparts. Ideological
      barriers included lack of SDOH awareness, narrow understandings of the relative
      influences of the SDOH, resistance to de-prioritizing healthcare, and
      conservative values. Advancement of a SDOH policy agenda should incorporate wider
      dissemination efforts to citizens and local service providers to increase support
      for this framework, and utilization of existing support and political engagement
      from liberal-leaning demographics.

PMID- 16621121
TI  - General Practitioners with special clinical interests: a qualitative study of the
      views of doctors, health managers and patients.
AB  - BACKGROUND: The difficulties with under-provision of doctors mean that
      alternative ways of providing services need to be developed. In the UK, some
      primary care doctors are now providing services traditionally only obtained
      through secondary care. The views of health care professionals, as well as
      patients, about these new services are currently unexplored. OBJECTIVES: To study
      the views of a variety of doctors, health managers and patients concerning the
      development of General Practitioners with special clinical interests. DESIGN:
      Qualitative using semi-structured audio-taped interviews. PARTICIPANTS: Health
      Service Managers, General Practice Registrars (GPRs), General Practitioners (GPs)
      with no special clinical interest, GPs with special clinical interests (GPSCIs),
      consultants (from specialties with and without GPSCIs) and patients who had
      attended a GPSCI clinic. SETTING: The North East of England. RESULTS: A range of
      positive benefits was identified for GPs with special clinical interests
      including enhanced job satisfaction and possibly increased recruitment and
      retention for general practice. They were expected to decrease hospital specialty
      waiting times and may address previously unmet needs. Patients appreciated the
      requirement of appropriate professional skill mixes for less serious conditions.
      Personal aspects of care were important for patients. Outcome measures appeared
      poorly defined. Negative aspects identified included a deskilling of the general
      pool of GPs and an increase in workload by treating previously untreated
      conditions. A variety of challenges in establishing these services (in particular
      proactive development of GPSCIs in areas of need, accreditation and governance)
      were uncovered and some potential solutions discussed. CONCLUSIONS: The impact of
      GPs with special clinical interests has not been studied in any detail, and
      measures of success for these schemes, where they exist, may fail to address the
      wide range of potential positive and negative effects. Their cost effectiveness
      has been questioned, and yet in the future more of these types of schemes seem
      likely. GPs with special interests may be part of an increasingly flexible career
      structure that sees GPs and secondary care doctors and consultants having much
      more interchangeable career paths. Patients' views on the services were generally
      positive.

PMID- 16621122
TI  - Quality of consultation and the project 'Support and Consultation on Euthanasia
      in the Netherlands' (SCEN).
AB  - OBJECTIVE: Consultation of another physician is one of the requirements for
      prudent practice. The project 'Support and Consultation on Euthanasia in the
      Netherlands' (SCEN) is aimed at professionalizing consultation. The objective of
      this study is to assess whether the quality of consultation was improved through
      SCEN. METHOD: In four districts all general practitioners (GPs) received a pre
      test questionnaire approximately six weeks before the start of the project in the
      period (n=1224, response 71%). In the period from April 2000 to December 2002,
      all GPs in districts in which SCEN had been implemented received a written post
      test questionnaire one and a half years after the start of the project. This post
      test questionnaire was returned by 60% of the GPs (n=3614). RESULTS: In SCEN
      consultations the attending physicians has no specific relation to the attending
      physician in 85% of consultations, while this is the case for 31% of other
      consultations. While before the start of SCEN in 71% of consultations six or
      seven of the seven criteria for good consultation were met, in SCEN consultations
      83% of cases six or seven of these requirements were met. GPS who had consulted a
      SCEN physician generally were more positive about different aspects than those
      who consulted another consultant, such as considering the consultant to be able
      to make an independent judgement (totally agree 74% versus 59%). CONCLUSION:
      Although the quality of consultation appears to be high for both SCEN physicians
      and other consultants, the SCEN project further contributed to the quality of
      consultation. Since GPs attach importance to judgement of SCEN physician and have
      the intention to use it in future, and the quality of consultation stays high
      over time, this project is expected to maintain its value.

PMID- 16621123
TI  - Policy through procurement - the introduction of digital signal process (DSP)
      hearing aids into the English NHS.
AB  - Despite being a major user of many technologies and innovations, the healthcare
      sector's role and influence as a procurer of technologies has been poorly
      represented by the literature and consequently is not fully understood. Providing
      a practical example of the introduction of digital signal process (DSP) hearing
      aids in to the English NHS, this paper discusses the role of public sector
      procurement agencies in the uptake of technologies from the private sector and
      their adoption by the public sector. Employing a system of innovation (SI)
      approach, the paper highlights the need for policy-makers to adopt a dynamic as
      well as systemic perspective that recognises the shifting roles, responsibilities
      and interactions of key stakeholders throughout the innovation process.

PMID- 16621124
TI  - Understanding the limited impact of economic evaluation in health care resource
      allocation: a conceptual framework.
AB  - Concern has increasingly been expressed at the low level of impact that economic
      evaluations have on the priority setting decisions they are designed to inform.
      The concern to maximise the impact of economic evaluation in health care is
      reminiscent of research utilisation debates rehearsed in the various policy
      studies disciplines. This paper draws on selected themes and frameworks from this
      literature in order to explore issues and map out an agenda relating to the
      uptake and use of cost effectiveness analysis in health policy decisions. The
      authors consider the implications for health economics, and other policy-related
      research and evaluation, of adopting either a rational or interactive model of
      research utilisation. Economic evaluations can be normative or descriptive
      decision tools. The choice of approach will reflect the assumed model of research
      utilisation and has implications for overcoming barriers to impact on policy.
      There is an underlying conceptual link between the rational model of research
      utilisation, the normative approach to economic evaluation and a focus on
      barriers to the accessibility of published analyses. In contrast, acknowledgement
      of an interactive and incremental policy process predisposes the analyst to a
      more descriptive approach and suggests the importance of broader systems, process
      and ethical barriers to the use of economic evaluation. We address the crucial
      issue of the importance of establishing objectives and discuss how this issue
      effects how those seeking to influence policy should proceed. Finally, we discuss
      indirect or 'enlightenment' models of research utilisation and the implications
      of these for the community of health economists.

PMID- 16621125
TI  - Cardiac health diagnosis using data fusion of cardiovascular and haemodynamic
      signals.
AB  - The electrocardiogram (ECG) is a representative signal containing useful
      information about the condition of the heart. The shape and size of the P-QRS-T
      wave, the r-r interval, etc., may help to identify the nature of disease
      afflicting the heart. However, human observer cannot directly monitor these
      subtle details and it is difficult to evaluate the cardiac health using ECG
      alone. Hence, the fusion of ECG, blood pressure, saturated oxygen content and
      respiratory data for achieving improved clinical diagnosis of patients in cardiac
      care units. In this study, a computer based analysis and display of the
      heterogeneous signals for the detection of life threatening states is
      demonstrated using fuzzy logic based data fusion. And to evaluate the severity of
      the disease a new parameter, deterioration index is proposed and results are
      tabulated for various cases.

PMID- 16621126
TI  - A new approach to systematization of the management of paper-based clinical
      pathways.
AB  - The present study was performed to explore a new approach to systematization of
      the management of paper-based clinical pathways by developing a new system
      requiring little capital investment. A new system was developed and incorporated
      into an existing network at a hospital with a paper-based clinical pathway
      management system. The effectiveness of this new system was examined by comparing
      the management efficiency of clinical pathways before and after its introduction,
      and by comparison of the new system with other such systems currently in place at
      other medical institutions with regard to efficiency. In addition, the
      acceptability of the system for other medical institutions was examined by
      providing free access to the software on the Internet. The development costs of
      the new system were low. Although the new system has been in place for more than
      3 years, no problems have yet been encountered in either the existing network
      system or in the management system itself. The new system allows the processing
      of statistics and analysis of circulation or variance automatically, neither of
      which were possible in the original paper-based system. We provided open access
      to the system as free software on the Internet, and it has since been downloaded
      by many medical institutions and enterprises in Japan. This system is very useful
      for institutions where it is difficult to introduce expensive new systems for
      systematic management of clinical pathways, such as electronic medical records,
      because of problems regarding capital or system management, and it may also be
      useful in other countries.

PMID- 16621127
TI  - Gaussian estimation and joint modeling of dispersions and correlations in
      longitudinal data.
AB  - Analysis of longitudinal, spatial and epidemiological data often requires
      modelling dispersions and dependence among the measurements. Moreover, data
      involving counts or proportions usually exhibit greater variation than would be
      predicted by the Poisson and binomial models. We propose a strategy for the joint
      modelling of mean, dispersion and correlation matrix of nonnormal multivariate
      correlated data. The parameter estimation for dispersions and correlations is
      based on the Whittle's [P. Whittle, Gaussian estimation in stationary time
      series, Bull Inst. Statist. Inst. 39 (1962) 105-129.] Gaussian likelihood of the
      partially standardized data which eliminates the mean parameters. The model
      formulation for the dispersions and correlations relies on a recent unconstrained
      parameterization of covariance matrices and a graphical method [M. Pourahmadi,
      Joint mean-covariance models with applications to longitudinal data:
      unconstrained parameterization, Biometrika 86 (1999) 677-690] similar to the
      correlogram in time series analysis. We show that the estimating equations for
      the regression and dependence parameters derived from a modified Gaussian
      likelihood (involving two distinct covariance matrices) are broad enough to
      include generalized estimating equations and its many recent extensions and
      improvements. The results are illustrated using two datasets.

PMID- 16621128
TI  - 3D finite element mesh generation of complicated tooth model based on CT slices.
AB  - An interactive three-dimensional finite element generation method is presented
      for modelling a multi-connected teeth and mandible structure. The tetrahedron is
      chosen as the basic element type due to its rigorous adaptability to structures
      with geometric complexities. The mesh generation is implemented by allocating two
      quadrangles in adjacent CT image slices to form a set of tetrahedrons. By
      examining all the possible allocations and their degradations, an algorithm is
      developed for interactive mesh generation, resulting in a series of tetrahedrons
      consistent with all the others without overlapping and spacing. The developed
      system was applied to a tooth-mandibular structure, generating a complicated 3D
      FEM model consisting of 4762 nodes and 18,534 tetrahedral elements with nine
      different materials. This 3D model was successfully used to evaluate different
      tooth restoration strategies, which proved the viability and effectiveness of the
      proposed method.

PMID- 16621129
TI  - Results of a Phase II study of weekly docetaxel and carboplatin in Stage IIIB
      (with effusion) or Stage IV non-small cell lung cancer patients age<or=65 and
      performance status 2.
AB  - This study explores if advanced NSCLC patients with ECOG PS 2 and age<or=65 years
      can benefit from weekly docetaxel+carboplatin, with acceptable toxicities. Fifty
      nine eligible patients with Stage IIIB (effusion) or Stage IV NSCLC were
      registered. Patients received docetaxel 35mg/m(2) and carboplatin AUC=2 on Days
      1, 8, and 15 every 28-day cycle (maximum 8 cycles). Endpoints were 1-year
      survival, tumor response, PFS, and safety. Among the 59 eligible patients, the 1
      year survival was 28% and median survival was 6 months (range: 1-24.3). The
      median duration of response for CR+PR was 5.4 months (range: 2.3-9.7), 1-year
      progression-free survival was 14% (median of 3.7 months, range<1-22.8). Patients
      received a median of 3 cycles (range: 1-9); 14 patients (24%) had toxicity
      related reductions. Responses were: 1 CR (2%), 5 PR (10%), 22 SD (45%), and 21 PD
      (43%). Forty-nine patients were evaluable for response; 10 patients were non
      evaluable due to: radiotherapy (1), withdrew consent (3), insurance issues (1),
      and early toxicity (1 each; dyspnea, weakness, and rash), and other illness (2).
      Fifty-eight patients were evaluable for safety. The primary Grade 3 or 4
      toxicities were neutropenia and fatigue (10% each), nausea (9%), dehydration
      (7%), and vomiting (5%). A 12% response rate (plus 45% SD) confirms the
      relatively poor outcome of patients with advanced NSCLC who are PS 2. Toxicities
      of docetaxel+carboplatin are comparable to other regimens and this combination
      may provide an alternative for this group of patients. Further studies
      correlating patient characteristics with response are necessary.

PMID- 16621130
TI  - Lack of response to erlotinib after progression on gefitinib in patients with
      advanced non-small cell lung cancer.

PMID- 16621131
TI  - A primary cell culture of Drosophila postembryonic larval neuroblasts to study
      cell cycle and asymmetric division.
AB  - Drosophila melanogaster is a key model system that has greatly contributed to the
      advance of developmental biology through its extensive and sophisticated
      genetics. Nevertheless, only a few in vitro approaches are available in
      Drosophila to complement genetic studies in order to better elucidate
      developmental mechanisms at the cellular and molecular level. Here we present a
      dissociated cell culture system generated from the optic lobes of Drosophila
      larval brain. This culture system makes it feasible to study the proliferative
      properties of Drosophila postembryonic Nbs by allowing BrdU pulse and chase
      assays, as well as detailed immunocytochemical analysis with molecular markers.
      These immunofluorescence experiments allowed us to conclude that localization of
      asymmetric cell division markers such as Inscuteable, Miranda, Prospero and Numb
      is cell autonomous. By time-lapse video recording we have observed interesting
      cellular features of postembryonic neurogenesis such us the polarized genesis of
      the neuroblast progeny, the extremely short ganglion mother cell (GMC) cell
      cycle, and the last division of a neuroblast lineage. The combination of this
      cell culture system and genetic tools of Drosophila will provide a powerful
      experimental model for the analysis of cell cycle and asymmetric cell division of
      neural progenitor cells.

PMID- 16621132
TI  - Photosynthetic activity, pigment composition and antioxidative response of two
      mustard (Brassica juncea) cultivars differing in photosynthetic capacity
      subjected to cadmium stress.
AB  - Photosynthetic performance, contents of chlorophyll and associated pigments,
      cellular damage and activities of antioxidative enzymes were investigated in two
      mustard (Brassica juncea L.) cultivars differing in photosynthetic capacity
      subjected to cadmium (Cd) stress. Exposure to Cd severely restricted the net
      photosynthetic rate (P(N)) of RH-30 compared to Varuna. This corresponded to the
      reductions in the activities of carbonic anhydrase (CA) and ribulose-1,5
      bisphosphate carboxylase (Rubisco) in both the cultivars. Decline in chlorophyll
      (Chl) (a+b) and Chl a content was observed but decrease in Chl b was more
      conspicuous in Varuna under Cd treatments, which was responsible for higher Chl
      a:b ratio. Additionally, the relative amount of anthocyanin remained higher in
      Varuna compared to RH-30 even in the presence of high Cd concentration, while
      percent pheophytin content increased in RH-30 at low Cd concentration. A higher
      concentration of Cd (100 mg Cd kg(-1) soil) resulted in elevated hydrogen
      peroxide (H(2)O(2)) content in both the cultivars. However, Varuna exhibited
      lower content of H(2)O(2) in comparison to RH-30. This was reflected in the
      increased cellular damage in RH-30, expressed by greater thiobarbituric acid
      reactive substances (TBARS) content and electrolyte leakage. The enhanced
      activities of antioxidative enzymes, ascorbate peroxidase (APX), catalase (CAT)
      and glutathione reductase (GR) and also lower activity of superoxide dismutase
      (SOD) in Varuna alleviated Cd stress and protected the photosynthetic activity.

PMID- 16621133
TI  - Red/far-red light modulates phospholipase D activity in oat seedlings: relation
      of enzyme photosensitivity to photosynthesis.
AB  - Phospholipase D (PLD) activity was found to be higher in etiolated oat seedlings
      than in green seedlings. White and red (R) light exposure inhibited PLD activity
      in etiolated seedlings. Far-red light eliminated R-light-induced decrease in PLD
      activity, indicating phytochrome participation in observed photomodulation.
      Inhibitor of electron transport in chloroplast 3-(3,4-dichlorophenyl)-1,1
      dimethylurea stimulated and glucose suppressed PLD activity in green and
      etiolated oat seedlings, respectively. These results suggest that PLD activity in
      oat seedling is regulated by light with involvement of phytochrome photoreceptor,
      and associated with photosynthesis process.

PMID- 16621134
TI  - Food attitudes, eating behavior, and the information underlying food attitudes.
AB  - This research examined healthiness perceptions and how the information underlying
      food attitudes more generally relate to attitudes and behaviors. Participants
      completed attitudinal measures and various card-sorting tasks in which they rank
      ordered foods (pictures and/or nutrition labels) in terms of healthiness. Taste
      was found to be a stronger predictor of attitudes and past eating behavior than
      other information underlying attitudes (health, guilt, comfort). Furthermore,
      participants' healthiness rankings of pictures were not correlated to rankings of
      the corresponding nutrition labels, suggesting that when determining a food's
      healthiness, participants do not rely on (or are not aware of) the actual
      nutritional makeup.

PMID- 16621135
TI  - Compliance with surgical antibiotic prophylaxis--reporting from a statewide
      surveillance programme in Victoria, Australia.
AB  - A statewide assessment of the compliance of surgical antibiotic prophylaxis (SAP)
      with guidelines was undertaken for large public hospitals in Victoria, Australia.
      This was carried out using data collected as part of a surveillance system for
      hospital-acquired infections. The study population comprised patients in
      Victorian public hospitals with >100 beds (N=27) undergoing cardiac surgical
      procedures, hip or knee arthroplasty, cholecystectomy, appendectomy, colon
      surgery or hysterectomy over a 21-month period. Australian guidelines recommend
      SAP for all 10 643 surgical procedures included in this study. Combining all
      procedures, 87% received SAP, the choice of antibiotic was concordant with
      guidelines for 53.3% of procedures, and the choice of antibiotic was considered
      to be 'adequate but not concordant' for 23.9% of procedures. SAP was considered
      to be inadequate for 18.9% of procedures. A large number of antibiotic regimens
      were utilized for cardiac and orthopaedic surgery. Documentation of timing of
      administration was not submitted for more than half of all procedures. Timing was
      concordant with guidelines for 76.4% of procedures when documented. Prophylactic
      antibiotic choice was generally more concordant with guidelines for cardiac and
      orthopaedic procedures than for other types of surgery. However, even for these
      procedures, where infections carry high morbidity, SAP was sometimes inadequate.
      Regular reporting on SAP compliance from data collected during surveillance for
      hospital-acquired infections is achievable. This should lead to improvements in
      both compliance and documentation.

PMID- 16621136
TI  - Legionella spp. in hospital dental facilities.

PMID- 16621137
TI  - Cost of intensive care unit-acquired bloodstream infections.
AB  - Intensive care unit-acquired (ICU-acquired) bloodstream infections (BSI) are an
      important complication of critical illness. The objective of this study was to
      quantify the excess length of stay, mortality and cost attributable to ICU
      acquired BSI. A matched cohort study was conducted in all adult ICUs in the
      Calgary Health Region between 1 May 2000 and 30 April 2003. One hundred and forty
      four patients with ICU-acquired BSI were matched (1:1) to patients without ICU
      acquired BSI. Patients with ICU-acquired BSI had a significantly increased median
      length of ICU stay {15.5 [interquartile range (IQR) 8-26] days vs 12 [IQR 7-18.5]
      days, P=0.003} and median costs of hospital care [85,137 dollars (IQR 45,740
      131,412 dollars) vs 67,879 dollars (IQR 35,043-115,915 dollars, P=0.02) compared
      with patients without ICU-acquired BSI. The median excess length of ICU stay was
      two days and the median cost attributable to ICU-acquired BSI was 12,321 dollars
      per case. Sixty (42%) of the cases died compared with 37 (26%) of the controls
      [P=0.002, attributable mortality 16%, 95% confidence interval (CI) 5.9-26.0%].
      Patients with ICU-acquired BSI were at increased risk for in-hospital death (odds
      ratio=2.64, 95%CI 1.40-5.29). Among survivor-matched pairs, the median excess
      lengths of ICU and hospital stay attributable to development of ICU-acquired BSI
      were two and 13.5 days, respectively, and the attributable cost due to ICU
      acquired BSI was 25,155 dollars per case survivor. Critically ill patients who
      develop ICU-acquired BSI suffer excess morbidity and mortality, and incur
      significantly increased healthcare costs. These data support expenditures on
      infection prevention and control programmes and further research into reducing
      the impact of these infections.

PMID- 16621138
TI  - Emergence of epidemic clones of vancomycin-resistant Enterococcus faecium in
      Singapore.

PMID- 16621139
TI  - Coverage of hepatitis B vaccination in Swedish healthcare workers.
AB  - The aim of this study was to assess how well the guidelines on vaccination
      against hepatitis B had been implemented among healthcare workers (HCWs) at risk
      for blood exposure. A point-prevalence survey was conducted in six departments of
      a university hospital in Sweden: the emergency room, intensive care unit,
      postoperative unit, surgical theatre, department of anaesthesiology and the
      laboratory for blood chemistry. All HCWs who worked in these departments during
      the 24h of the survey were asked to complete a questionnaire. In total, 369
      questionnaires were analysed. Seventy-nine percent (293/369) of HCWs had received
      at least one dose of vaccine, but only 40% (147/369) reported that they were
      fully vaccinated and 21% (76/369) had not been vaccinated at all. The majority of
      unvaccinated HCWs (72/76, 95%) stated that they would accept vaccination if
      offered. The main barrier to better compliance with the guidelines is not lack of
      acceptance among the employees but the failure of the employer to ensure that
      policies are implemented.

PMID- 16621140
TI  - Should doctors wear ties?

PMID- 16621141
TI  - Meticillin-sensitive and -resistant Staphylococcus aureus: competition and co
      carriage.

PMID- 16621142
TI  - A practical tool to assess the incidence of nosocomial infection in Japanese
      intensive care units: the Japanese Nosocomial Infection Surveillance System.
AB  - SUMMARY: Infection control professionals have the means to calculate infection
      rates in their hospitals but not to assess them. They require a practical tool
      that enables them to compare observed infection rates with external standards.
      Based on the data obtained from the intensive care unit (ICU) component of the
      Japanese Nosocomial Infection Surveillance (JANIS) system, a spreadsheet was
      developed to calculate a standardized infection ratio (SIR) as a risk-adjusted
      indicator. Out of the factors associated with the development of nosocomial
      infections in a multi-variate analysis, the following three factors were selected
      for stratification: APACHE II score (0-10, 11-20, 21+), operation (yes, no) and
      ventilator use (user, non-user). Infection rates in 2001 were determined (per
      1000 patient-days), stratified by the three factors, as a benchmark. The
      spreadsheet was designed to calculate SIRs on the basis of the Japanese benchmark
      infection rates using Microsoft Excel software. The user of the spreadsheet
      should input the number of observed nosocomial infections and patient-days by
      APACHE II score, operation and ventilator use. When applied to eight Japanese
      ICUs, the spreadsheet revealed relative differences and temporal changes in the
      incidence of nosocomial infections within these ICUs.

PMID- 16621143
TI  - Point-of-care controls for nosocomial legionellosis.

PMID- 16621144
TI  - Further bacteriological evaluation of the TOUL mobile system delivering ultra
      clean air over surgical patients and instruments.
AB  - Two mobile TOUL-400 units (types 1 and 2) that produce an exponential ultra-clean
      air flow (EUA) via a mobile screen were evaluated (maximum height from floor to
      centre of screen: type 1, 1.4m; type 2, 1.6m). Bacterial deposition rates were
      lowered by >60% (P=0.001) over a table area of 1.7 m (length)x1.0m (width) with
      the TOUL-400 type 1 unit, and the mean air count at 1.0m from the screen was
      reduced from 23 to 1.6 colony-forming units (CFU)/m3 in experiments in a room
      with six air changes/h (ACH). The corresponding reductions were two- to three
      fold greater in an operating room (OR) with 16 ACH due to higher bacterial
      contamination levels in the control experiments. The dramatic but localized
      reduction of the deposition rate recorded on one 14-cm settle plate (>2376-fold
      at 0.8m from the screen in the OR) apparently reflected the focus of the EUA. The
      impact of the TOUL-400 unit was underestimated by almost 100-fold by the air
      counts of bacteria recorded in parallel at the same sampling point (26.5-fold
      reduction). During sham coronary angiography and sham hip arthroplasty performed
      in a room with six ACH, ultra-clean air (<10 CFU/m3) was obtained over the
      incision area with the TOUL-400 type 2 unit when the EUA was undisturbed (maximum
      screen-wound distance 1.7 m). In actual coronary angiography (room with six ACH,
      screen-wound distance 2.0-2.3m) and various surgical procedures in the OR (screen
      wound distance 1.4-1.8m), ultra-clean air was obtained at the wound in three of
      18 instances, characterized by undisturbed air flow and a maximum distance of 1.8
      m. The newly developed TOUL-300 surgical instrument table (1.3-1.7 x 0.6m),
      equipped at one end with the same EUA unit as the TOUL-400 unit, was evaluated
      for a room with six ACH and an OR with 16 ACH. It yielded ultra-clean air at 0.8m
      (1.9 CFU/m3, 96% reduction, P=0.01) and reduced the deposition rate by >60% over
      most of the table surface. Simplified positioning of the screen or a longer
      reach, plus a mechanism for precise focusing of the air flow on to the wound area
      would increase the clinical utility of the TOUL EUA system.

PMID- 16621145
TI  - Deep wound infection after proximal femoral fracture: consequences and costs.
AB  - The purpose of this study was to assess the impact of deep wound infection after
      surgery for proximal femoral fracture (PFF) on the patient in terms of mortality
      and social consequences, and on the National Health Service in terms of financial
      burden. Sixty-one cases of PFF over a six-year period were complicated with deep
      surgical wound infection. These cases were compared with a matched control group
      of 122 patients without infection. Infected cases had greatly increased hospital
      stay (P<0.001), were 4.5 times less likely to survive to discharge (P=0.002), and
      if they survived, were three times less likely to return to their original
      residence (P=0.05). The total cost of treatment per infected case was 24,410
      pound sterling compared with 7210 pound sterling for controls (P<0.001).
      Meticillin-resistant Staphylococcus aureus (MRSA) infection increased admission
      length and cost compared with non-MRSA infection (P=0.02). Deep wound infection
      after PFF is a devastating and costly complication for both the patient and the
      healthcare services. The cost consequences should be considered when allocating
      resources to trauma services to ensure adequate provision to minimize infection
      risks and to accommodate treatment costs in this vulnerable group.

PMID- 16621146
TI  - Interaction of the tachykinin NK3 receptor agonist senktide with behavioral
      effects of cocaine in marmosets (Callithrix penicillata).
AB  - Brain neuropeptide transmitters of the tachykinin family are involved in the
      organization of many behaviors. However, little is known about their contribution
      to the behavioral effects of drugs of abuse. Recently, antagonism of the
      tachykinin NK3-receptor (NK3-R), one of the three tachykinin receptors in the
      brain, was shown to attenuate the acute and chronic behavioral effects of cocaine
      in rats and the acute effects in non-human primates. In order to expand these
      findings we investigated the effects of the NK3-R agonist, succinyl-[Asp6, Me
      Phe8]SP(6-11) (senktide), on the acute behavioral effects of cocaine in marmoset
      monkeys (Callithrix penicillata) using a figure-eight maze procedure. Animals
      were pretreated with senktide (0, 0.1, 0.2, 0.4 mg/kg, s.c.), and received either
      a treatment with cocaine (10 mg/kg) or saline (i.p.). Cocaine increased locomotor
      activity and the duration of aerial scanning behavior, but reduced exploratory
      activity, bodycare activity, the frequency of aerial scanning, and terrestrial
      glance behavior. Senktide blocked the effects of cocaine on locomotor activity,
      but enhanced the cocaine effects on exploratory activity, aerial scanning
      frequency, and terrestrial glance behavior. Senktide alone did not significantly
      influence monkey behavior in this study. These data expand previous findings
      suggesting a complex role of the NK3-R in the acute behavioral effects of cocaine
      in non-human primates.

PMID- 16621147
TI  - Pre-treatment of central venous catheters with the cathelicidin BMAP-28 enhances
      the efficacy of antistaphylococcal agents in the treatment of experimental
      catheter-related infection.
AB  - An in vitro antibiotic susceptibility assay for Staphylococcus aureus biofilms
      developed on 96-well polystyrene tissue culture plates was performed to elucidate
      the activity of the 27 residues cathelicidin peptide BMAP-28,
      quinupristin/dalfopristin (Q/D), linezolid, and vancomycin. Efficacy studies were
      performed in a rat model of staphylococcal CVC infection. Silastic catheters were
      implanted into the superior cava. Twenty-four hours after implantation the
      catheters were filled with BMAP-28. Thirty minutes later rats were challenged via
      the CVC with 1.0x10(6) CFU of S. aureus strain Smith diffuse. Administration of
      antibiotics into the CVC at a concentration equal to the MBC observed using
      adherent cells, or at a much higher concentration (1024 microg/mL) began 24 h
      later. The inhibition activities of all antibiotics against adherent bacteria
      were at least two-four-fold lower that against freely growing cells. When
      antibiotics were used in BMAP-28 pre-treated wells, they showed higher
      activities. The in vivo studies showed that when CVCs were pre-treated with BMAP
      28 or with a high dose of antibiotics, biofilm bacterial load was reduced from
      10(7) to 10(3) CFU/mL and bacteremia reduced from 10(3) to 10(1) CFU/mL. When
      CVCs were treated with both BMAP-28 and antibiotics, biofilm bacterial load was
      further decreased to 10(1) CFU/mL and bacteremia was not detected. These results
      suggest that CVC pre-treated with BMAP-28 represents an attractive choice for the
      treatment of device-related infections caused by staphylococci.

PMID- 16621148
TI  - RFamide peptides. Introduction.

PMID- 16621149
TI  - Neurohormones and inflammatory mediators in patients with heart failure
      undergoing cardiac resynchronization therapy: time courses and prediction of
      response.
AB  - Despite interest in neurohormonal activation as a determinant of prognosis in
      chronic heart failure (CHF) and as a target for pharmacological treatments, data
      are lacking on the time-related effects of electrical cardiac resynchronization
      therapy (CRT) on a broad spectrum of neurohormones and cytokines. The aim of this
      study was to assess time-courses and extents of changes within the neurohormonal
      profile of CHF patients treated with CRT. We performed a prospective follow-up
      study in 32 patients with NYHA class III-IV CHF to investigate the effects of CRT
      on a broad panel of neurohormones proposed for characterization of CHF patients.
      Levels of atrial and brain natriuretic peptides (ANP, BNP), epinephrine,
      norepinephrine, aldosterone, plasma renin activity, IL-6, TNF, soluble receptors
      sTNFR1 and 2, and chromogranin A were assessed before implantation and after 3
      months of CRT; when feasible, measurements were also performed at 1 week, 1 month
      and 12 months (clinical evaluation, echocardiography and ECG were also performed
      at each time-point). The results showed that at 3 months improvement in NYHA
      class and echographically assessed left ventricular (LV) reverse structural
      remodeling were accompanied by significant reductions versus baseline in ANP and
      BNP, but not in other neurohormones. Moreover a baseline ANP concentration < or =
      150 pg/ml was a good predictor of response to CRT in terms of NYHA class
      reduction and reverse LV remodeling. In conclusion 3 months of CRT significantly
      reduce natriuretic peptides concentrations, while values of other neurohormones
      and inflammatory cytokines are relatively unvaried. A baseline ANP concentration
      < or = 150 pg/ml might be a clinically useful predictor of medium-term response
      to CRT.

PMID- 16621150
TI  - A hemoglobin fragment found in cervicovaginal fluid from women in labor
      potentiates the action of agents that promote contraction of smooth muscle cells.
AB  - We employed a proteomic approach to search for peptides that have a physiological
      role in labor. Cervicovaginal secretions were collected at term from women in
      labor and women at term not in labor. Samples were spotted onto weak cation
      exchange chips (WCX-2) and analyzed using Surface-Enhanced Laser Desorption
      Ionization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). Spectra were obtained
      for each sample and Biomarker Wizard analysis revealed 25 peaks that had
      significantly different peak intensity between the labor and non-laboring women.
      The sequences of five peaks that were significantly elevated in the labor cohort
      were determined using Protein Chip Interface Quadruple Time-of-Flight Mass
      Spectrometry (PCI-QTOF-MS). All of these peaks were identified as fragments of
      alpha or beta-hemoglobin (Hb). A 2.022 kDa fragment of alpha-Hb (amino acids 110
      128, NH2-AAHLPAEFTPAVHASLDKF-COOH) was found to potentiate smooth muscle cell
      contraction in response to bradykinin, oxytocin and prostaglandin-F2alpha. This
      peptide may promote vasoconstriction and augment normal labor through enhancing
      the action of uterotonins.

PMID- 16621151
TI  - Human VIP-alpha: a long-acting, biocompatible and biodegradable peptide
      nanomedicine for essential hypertension.
AB  - We have previously shown that self-association of human vasoactive intestinal
      peptide with sterically stabilized liposomes (VIP-alpha) alters peptide
      conformation from random coil in aqueous solution to alpha-helix. This, in turn,
      protects the peptide from hydrolysis and amplifies and prolongs its bioactivity.
      The purpose of this study was to determine whether a single, intravenous
      injection of low-dose human VIP-alpha normalizes systemic arterial pressure in
      anesthetized spontaneously hypertensive hamsters for a prolonged period of time
      in a selective fashion. We found that intravenous injection of human VIP-alpha,
      VIP alone (each, 1.0 nmol) and empty liposomes had no significant effects on mean
      arterial pressure (MAP) in normotensive hamsters. By contrast, human VIP-alpha
      (0.01-1.0 nmol) evoked a significant concentration-dependent decrease in MAP to
      the normative range in spontaneously hypertensive hamsters that lasted throughout
      the observation period (6 h; p<0.05). VIP alone and empty liposomes had no
      significant effects on MAP in these animals. We conclude that a single, low-dose
      intravenous injection of human VIP-alpha normalizes systemic arterial pressure in
      spontaneously hypertensive hamsters for a prolonged period of time in a selective
      fashion. We suggest that human VIP-alpha should be further developed as a long
      acting, biocompatible and biodegradable peptide nanomedicine for essential
      hypertension.

PMID- 16621152
TI  - The Chinese bamboo leaf odorous frog (Rana (Odorrana) versabilis) and North
      American Rana frogs share the same families of skin antimicrobial peptides.
AB  - The Chinese bamboo leaf odorous frog (Rana (Odorrana) versabilis) and the North
      American pickerel frog (Rana palustris) occupy different ecological niches on two
      different continents with no overlap in geographical distribution. R. palustris
      skin secretions contain a formidable array of antimicrobial peptides including
      homologs of brevinin-1, esculentin-1, esculentin-2, ranatuerin-2, a temporin and
      a family of peptides considered of unique structural attributes when isolated,
      palustrins 1-3. Here we describe the structures of mature peptides and precursors
      of eight putative antimicrobial peptides from the skin secretion of the Chinese
      bamboo leaf odorous frog (Rana (Odorrana) versabilis). Each peptide represents a
      structural homolog of respective peptide families isolated from R. palustris,
      including two peptides identical in primary structure to palustrin 1c and
      palustrin 3b. Additionally, two peptides were found to be structural homologs of
      ranatuerin 2B and ranatuerin 2P from the closely-related North American species,
      Rana berlandieri (the Rio Grande leopard frog) and Rana pipiens (the Northern
      leopard frog), respectively. Both palustrins and ranatuerins have hitherto been
      considered unique to North American ranid frogs. The use of primary structures of
      amphibian skin antimicrobial peptides is thus questionable as a taxonomic device
      or alternatively, the micro-evolution and/or ancestry of ranid frogs is more
      highly complex than previously thought.

PMID- 16621153
TI  - Leptin transgene expression in the hypothalamus enforces euglycemia in diabetic,
      insulin-deficient nonobese Akita mice and leptin-deficient obese ob/ob mice.
AB  - We have tested the hypothesis that sustained leptin action in the hypothalamus
      alone can engender and maintain euglycemia in wild type mice and in two monogenic
      diabetic models, the insulin-deficient nonobese Akita mice and the
      hyperinsulinemic leptin-deficient obese, ob/ob mice. A single
      intracerebroventricular injection of recombinant adeno-associated virus vector
      encoding leptin (rAAV-lep) enhanced leptin transgene expression in the
      hypothalamus without any evidence of leptin leakage to the peripheral
      circulation, and promptly reinstated euglycemia that persisted along with severe
      insulinopenia in all three genotypes through the 7-week period of observation. A
      comparative evaluation of known etiologic factors of hyperglycemia showed that
      this long-term benefit on glucose homeostasis was not due to diminished energy
      consumption, weight and adiposity, but was conferred by at least two mechanisms
      operating simultaneously, enhanced glucose metabolism to meet the demand for the
      rAAV-lep induced increased non-shivering thermogenesis mediated by brown adipose
      tissue and insulin hypersensitivity. These findings endorse the hypothesis that
      increased leptin action locally in the hypothalamus can impose euglycemia
      independent of pancreatic insulin, and central leptin reinforcement may serve as
      a newer adjunct therapy to treat type 1 and type 2 diabetes.

PMID- 16621154
TI  - Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in
      the rat.
AB  - Previous work has shown that arginine vasopressin (AVP) regulates antinociception
      through brain nuclei rather than the spinal cord and peripheral organs. The
      present study investigated the nociceptive effect of AVP in the nucleus raphe
      magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain
      threshold in a dose-dependent manner, while local administration of AVP-receptor
      antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation
      elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP
      receptor antagonist completely reversed AVP's effect on pain threshold in the
      NRM. The data suggest that AVP in the NRM is involved in antinociception.

PMID- 16621155
TI  - Antimicrobial peptides from diverse families isolated from the skin of the Asian
      frog, Rana grahami.
AB  - Seven peptides with antimicrobial activity were isolated in pure form from an
      extract of the skin of the Yunnanfu Kunming frog Rana grahami Boulenger, 1917.
      The peptides were identified as belonging to the nigrocin-2 (three peptides),
      brevinin-1 (one peptide), brevinin-2 (three peptides), and esculentin-1 (one
      peptide) families. Nigrocin-2GRb (GLFGKILGVGKKVLCGLSGMC) containing three lysine
      residues, represented the peptide with highest potency against microorganisms
      (MIC = 3 microM against Escherichia coli, 12.5 microM against Staphylococcus
      aureus and 50 microM against Candida albicans) and the greatest hemolytic
      activity against human erythrocytes (LD50 = 40 microM). In contrast, nigrocin
      2GRa (GLLSGILGAGKHIVCGLSGLC) and nigrocin-2GRc (GLLSGILGAGKNIVCGLSGLC), with only
      a single lysine residue, showed weak antimicrobial and hemolytic activity.
      Phylogenetic relationships among Eurasian ranid frogs are less well understood
      than those of North American ranids but the primary structures of the R. grahami
      antimicrobial peptides suggest a close relationship of this species with the
      Japanese pond frogs R. nigromaculata and R. porosa brevipoda.

PMID- 16621156
TI  - Melanin-concentrating hormone (MCH) reverts the behavioral effects induced by
      inescapable stress.
AB  - The aim of this work was to investigate if MCH modifies the feeding and freezing
      responses in rats exposed to stressful stimuli. We used a basic version of
      contextual fear, where one group of rats were placed in a novel environment and
      two different groups were exposed to footshock paradigms, one of them escapable
      and the other one inescapable. At the end of each treatment, freezing and feeding
      were measured. Only the animals exposed to inescapable footshock paradigm showed
      significant increase in the food intake and freezing behavior in comparison to
      the control animals. The MCH administration (intra-hippocampal or intra
      amygdaline) reverted these effects elicited by inescapable footshock. Results
      presented in this paper lead us to the assumption that the anxiolytic effect of
      the peptide is responsible for the reversion of the IS effects.

PMID- 16621157
TI  - Proenkephalin A 119-159, a stable proenkephalin A precursor fragment identified
      in human circulation.
AB  - In this report, we describe a newly developed sandwich immunoassay using
      antibodies against the proenkephalin A 119-159 peptide (PENK A 119-159). PENK A
      119-159 immunoreactivity was detectable in the circulation of human blood donors
      and in cerebrospinal fluid (CSF) of patients without a neurologic disorder. The
      concentration was about 100 times higher in CSF than in serum. Analytical
      reversed phase HPLC revealed that PENK A 119-159 is the main immunoreactivity in
      human circulation and CSF. Moreover, PENK A 119-159 is stable in vitro for at
      least 48 h at room temperature as compared to the low stability of the peptides
      methionine- and leucine-enkephalin. This suggests the use of PENK A 119-159
      measurement as surrogate molecule for the release of the mature peptides derived
      from proenkephalin A.

PMID- 16621158
TI  - IL-1beta regulation of BDNF expression in rat cultured hypothalamic neurons
      depends on the presence of glial cells.
AB  - In the present study, we have shown that IL-1beta increased BDNF mRNA expression
      in hypothalamic neuron-enriched cultures whereas it reduced this expression in
      mixed cultures, i.e. containing astrocytes and neurons. Because functional
      relationships between stress and immunity signals are well documented we
      investigated the possible interaction between BDNF and IL-1beta in hypothalamic
      neurons. Notably, we investigated whether IL-1beta affected BDNF expression in
      vitro either on hypothalamic mixed cultures or on neuron-enriched cultures. We
      found that the response to IL-1beta was stimulatory when directly examined in
      neurons but was inhibitory when astrocytes were present in the cultures. Since it
      has been documented that astrocytes release PGE2 in response to IL-1beta, we
      examined the effect of indomethacin (a PGE2 synthesis inhibitor) on mixed or
      neuron-enriched cultures treated with IL-1beta. Indomethacin blocked both
      stimulatory and inhibitory IL-1beta effects on BDNF mRNA expression whereas
      picrotoxin (a GABA(A) blocker) or MK-801 (a NMDA receptor blocker) had no effect
      on BDNF mRNA levels. About 3 and 6h treatments of cells with exogenous PGE2
      reproduced the effects of IL-1beta on neuron-enriched or on mixed cultures
      suggesting that PGE2 was involved in BDNF mRNA regulation. Analysis of PGE2
      receptors mRNA expression revealed that the PGE2 receptor pattern was changed
      when neuron-enriched cultures were treated with conditioned medium produced by
      astrocytes treated with IL-1beta. Thus, EP3 mRNA levels were increased while EP1
      and EP4 messengers were unchanged. This increased expression of the inhibitory
      prostaglandin receptor under astrocyte influence can explain the inhibition of
      BDNF mRNA levels observed in mixed cultures following IL-1beta or PGE2 treatment.
      Finally, we demonstrated by immunocytochemistry that EP3 receptors had a neuronal
      localization in the hypothalamic cultures. Taken together, these data contribute
      to underline an emerging physiological concept postulating that a same molecule
      may have opposite effects as a function of the cellular context.

PMID- 16621159
TI  - Modulation of NMDA receptors by AKT kinase.
AB  - The aim of the present work was to assess whether Akt modulates NMDA receptor
      function in cerebellar neurons in culture. Forskolin increases cAMP and activates
      Akt and NMDA receptors. In neurons treated with forskolin, intracellular calcium
      increased to 296 +/- 38% and this was completely prevented by inhibition of Akt.
      This indicates that, in these neurons, cAMP modulates NMDA receptors via Epac and
      Akt. Brain derived neurotrophic factor (BDNF) increases phosphorylation (and
      activity) of Akt to 350 +/- 60% of basal and also potentiates the increase of
      calcium and in cGMP induced by NMDA. BDNF-induced potentiation of NMDA receptor
      function is completely prevented by inhibition of PI3 kinase or of Akt. This
      indicates that BDNF modulates NMDA receptor function via PI3 kinase and Akt.
      Activation of NMDA receptors also leads to phosphorylation and activation of Akt
      which, in turn, potentiates NMDA receptor activation. The results reported
      indicate that when Akt activity increases the activation of NMDA receptors by its
      agonists also increases. Akt may play important roles in the modulation of NMDA
      receptor responses by other neurotransmitters and modulators and in the
      adaptation of NMDA receptor function to the physiological environmental
      conditions.

PMID- 16621160
TI  - Inhibitory effect of hemicholinium-3 on presynaptic nicotinic acetylcholine
      receptors located on the terminal region of myenteric motoneurons.
AB  - Previously we have demonstrated the presence of presynaptic nicotinic
      acetylcholine receptors on the terminals of myenteric neurons in Auerbach's
      plexus of guinea-pig ileum. During these studies we observed, that the presence
      of hemicholinium-3, an inhibitor of the high affinity choline uptake
      significantly influences the contraction of the longitudinal muscle strip
      preparation. Our aim was to investigate the neurochemical background of this
      effect and quantitatively characterize the action of HC-3. We studied the effect
      of HC-3 on epibatidine- and electrical stimulation-evoked contraction and release
      of [3H]acetylcholine from the guinea-pig longitudinal muscle strip preparation.
      We found that in the presence of tetrodotoxin, when the contribution of
      somatodendritic nicotinic acetylcholine receptors to the response was prevented
      due to the inhibition of axonal conduction, HC-3 inhibited the epibatidine-evoked
      contraction and [3H]acetylcholine release in the submicromolar range (IC50 = 897
      nM and IC50 = 693 nM, respectively), whereas the electrical stimulation-evoked
      contraction was not affected by HC-3, and the release of [3H]acetylcholine was
      apparently enhanced. Our data indicate that HC-3 inhibits the presynaptic
      nicotinic acetylcholine receptors of myenteric neurons. Since these receptors
      play an important role in the regulation of cholinergic neurotransmission in the
      enteric nervous system, the use of HC-3 in [3H]acetylcholine release experiments
      might bias the interpretation of data.

PMID- 16621161
TI  - Pharmacological properties of glycine uptake in the developing rat retina.
AB  - A pharmacological characterization of glycine transport was performed in the rat
      retina at different postnatal ages. The uptake of 3H-glycine increased during the
      first 2 weeks of postnatal age, reaching maximum values at 12 days; then it
      decreased sharply to the adult values. We found a Na+ -dependent and high
      affinity transport system with a Km of 100 microM. The Na+ Hill coefficient for
      glycine uptake was 1.76 +/- 0.07. Although glycine uptake was insensitive to
      staurosporine and phorbol ester, it was reduced 40-50% by sarcosine and ALX5407.
      Besides, amoxapine inhibited glycine uptake by 40 and 70% in adult and immature
      retina, respectively. These results suggest that the Glyt1 transporter was
      concentrated in the nerve terminals. In addition to the presence of Glyt1 in the
      retina, our results provided evidence of the occurrence of Glyt2 and/or another
      isoform of glycine transporter, which might have had a role in the retina
      development.

PMID- 16621162
TI  - Single and combined effects of carbamazepine and vinpocetine on depolarization
      induced changes in Na+, Ca2+ and glutamate release in hippocampal isolated nerve
      endings.
AB  - The single and combined effects of carbamazepine and vinpocetine on the release
      of the excitatory amino acid neurotransmitter glutamate, on the rise in internal
      Na+ (Na(i), as determined with SBFI), and on the rise in internal Ca2+ (Ca(i), as
      determined with fura-2) induced by an increased permeability of presynaptic Na+
      channels, with veratridine, or by an increased permeability of presynaptic Ca2+
      channels with high K+, were investigated in isolated hippocampal nerve endings.
      The present study shows that carbamazepine and vinpocetine, both inhibit dose
      dependently the release of preloaded [3H]Glu induced by veratridine. However,
      carbamazepine is two orders of magnitude less potent than vinpocetine. The
      calculated IC(50)'s for carbamazepine and vinpocetine to inhibit veratridine
      induced [3H]Glu release are 200 and 2 microM, respectively. Consistently 150
      microM carbamazepine and 1.5 microM vinpocetine reduce the veratridine-induced
      rise in Na(i) in a similar extent. The single effects of carbamazepine and of
      vinpocetine on the presynaptic Na+ channel mediated responses, namely the rise in
      Na(i) and the release of Glu induced by veratridine, are additive. Responses that
      depend on the entrance of external Ca2+ via presynaptic Ca2+ channels, such as
      the release of [3H]Glu and the rise in Ca(i) induced by high K+, are insensitive
      to 300 microM carbamazepine and slightly reduced by 5 microM vinpocetine. It is
      concluded that the additive effects of carbamazepine, which is one of the most
      common antiepileptic drugs, and vinpocetine that besides its known
      neuroprotective action and antiepileptic potential is a memory enhancer, may
      perhaps be advantageous in the treatment of epileptic patients.

PMID- 16621163
TI  - Apotransferrin decreases the response of oligodendrocyte progenitors to PDGF and
      inhibits the progression of the cell cycle.
AB  - In the CNS, transferrin (Tf) is expressed by the oligodendroglial cells (OLGcs)
      and is essential for their development. We have previously shown that
      apotransferrin (aTf) accelerates maturation of OLGcs in vivo as well as in vitro.
      The mechanisms involved in this action appear to be complex and have not been
      completely elucidated. The aim of this study was to investigate if Tf
      participates in the regulation of the cell cycle of oligodendroglial progenitor
      cells (OPcs). Primary cultures of OPcs were treated with aTf and/or with
      different combinations of mitogenic factors. Cell cycle progression was studied
      by BrdU incorporation, flow cytometry and by the expression of cell cycle
      regulatory proteins. Apotransferrin decreased the number of BrdU+ cells,
      increasing the cell cycle time and decreasing the number of cells in S phase. The
      cell cycle inhibitors p27kip1, p21cip1 and p53 were increased, and in agreement
      with these results, the activity of the complexes involved in G1-S progression
      (cyclin D/CDK4, cyclin E/CDK2), was dramatically decreased. Apotransferrin also
      inhibited the mitogenic effects of PDGF and PDGF/IGF on OPcs, but did not affect
      their proliferation rate in the presence of bFGF, bFGF/PDGF or bFGF/IGF. Our
      results indicate that inhibition of the progression of the cell cycle of OPcs by
      aTf, even in the presence of PDGF, leads to an early beginning of the
      differentiation program, evaluated by different maturation markers (O4, GC and
      MBP) and by morphological criteria. The modulation by aTf of the response of OPcs
      to PDGF supports the idea that this glycoprotein might act as a key regulator of
      the OLGc lineage progression.

PMID- 16621164
TI  - Expression of CXC chemokine receptors 1-5 and their ligands in human glioma
      tissues: role of CXCR4 and SDF1 in glioma cell proliferation and migration.
AB  - Chemokines have been involved in cellular processes associated to malignant
      transformation such as proliferation, migration and angiogenesis. The expression
      of five CXC chemokine receptors and their main ligands was analysed by RT-PCR in
      31 human astrocytic neoplasms. The mRNAs for all the receptors analysed were
      identified in a high percentage of tumours, while their ligands showed lower
      expression. CXCR4 and SDF1 were the most frequently mRNA identified (29/31 and
      13/31 of the gliomas studied, respectively). Thus, we further analysed the cell
      localization of CXCR4 and SDF1 in immunohistochemistry experiments. We show a
      marked co-localization of CXCR4 and SDF1 in tumour cells, mainly evident in
      psudolpalisade and microcystic degeneration areas and in the vascular
      endothelium. In addition, hSDF1alpha induced a significant increase of DNA
      synthesis in primary human glioblastoma cell cultures and chemotaxis in a
      glioblastoma cell line. These results provide evidence of the expression of
      multiple CXC chemokines and their receptors in brain tumours and that in
      particular CXCR4 and SDF1 sustain proliferation and migration of glioma cells to
      promote malignant progression.

PMID- 16621165
TI  - Changes in neuropeptide expression in mice infected with prions.
AB  - Prion diseases are neurodegenerative disorders characterized by accumulation of
      an aberrantly folded isoform (PrP(Sc)) of the normal prion protein (PrP(C)).
      Using in situ hybridization and immunohistochemistry, we have studied changes in
      the expression of neuropeptides, acetylcholinesterase and tyrosine hydroxylase in
      CD1 and FVB wild-type mouse strains, as well as in PrP(C) null mice and in mice
      overexpressing PrP(C) following intracerebral inoculation with RML or Me7 prions.
      In the immunohistochemical analysis, neuropeptide Y (NPY), enkephalin and
      dynorphin-like immunoreactivities increased in mossy fibers of CD1 and FVB mice
      inoculated with either RML- or Me7 prions, whereas cholecystokinin-like
      immunoreactivity was decreased. These changes in peptide levels were paralleled
      by an increase in the transcripts in granule cells for neuropeptide Y,
      enkephalin, and cholecystokinin. However, the dynorphin transcript was decreased
      in the granule cells. The changes occurred more rapidly in PrP(C)-overexpressing
      compared to wild-type mice, and could not be found at all in PrP(C)-knockout
      mice. These changes in peptide expression, which mostly occur before appearance
      of symptoms of disease, may reflect attempts to initiate protective and/or
      regenerative processes.

PMID- 16621166
TI  - Decreased sensitivity to phase-delaying effects of moderate intensity light in
      older subjects.
AB  - Aging is associated with a change in the relationship between the timing of sleep
      and circadian rhythms, such that the rhythms occur later with respect to sleep
      than in younger adults. To investigate whether a difference in the phase-delaying
      response to evening light contributes to this, we conducted a 9-day inpatient
      study in 10 healthy older (> or =65 y.o.) subjects. We assessed circadian phase
      in a constant routine, exposed each subject to a 6.5h broad-spectrum light
      stimulus beginning in the early biological night, and reassessed circadian phase.
      The stimuli spanned a range from very dim (approximately 2 lx) to very bright
      (approximately 8000 lx) indoor light. We found a significant dose-response
      relationship between illuminance and the phase shift of the melatonin rhythm,
      with evidence that sensitivity, but not the maximal response to light, differed
      from that of younger adults. These findings suggest an age-related reduction in
      the phase-delaying response to moderate light levels. However, our findings alone
      do not explain the altered phase relationship between sleep and circadian rhythms
      associated with aging.

PMID- 16621167
TI  - Angiotensin type-1-receptor antagonists reduce 6-hydroxydopamine toxicity for
      dopaminergic neurons.
AB  - Angiotensin II activates (via type 1 receptors) NAD(P)H-dependent oxidases, which
      are a major source of superoxide, and is relevant in the pathogenesis of several
      cardiovascular diseases and certain degenerative changes associated with ageing.
      Given that there is a brain renin-angiotensin system and that oxidative stress is
      a key contributor to Parkinson's disease, we investigated the effects of
      angiotensin II and angiotensin type 1 (AT(1)) receptor antagonists in the 6
      hydroxydopamine model of Parkinson's disease. Rats subjected to intraventricular
      injection of 6-hydroxydopamine showed bilateral reduction in the number of
      dopaminergic neurons and terminals. Injection of angiotensin alone did not induce
      any significant effect. However, angiotensin increased the toxic effect of 6
      hydroxydopamine. Rats treated with the AT(1) receptor antagonist ZD 7155 and then
      6-hydroxydopamine (with or without exogenous administration of angiotensin)
      showed a significant reduction in 6-hydroxydopamine-induced oxidative stress
      (lipid peroxidation and protein oxidation) and dopaminergic degeneration.
      Dopaminergic degeneration was also reduced by the NAD(P)H inhibitor apocynin.
      Angiotensin may play a pivotal role, via AT(1) receptors, in increasing the
      oxidative damage of dopaminergic cells, and treatment with AT(1) antagonists may
      reduce the progression of Parkinson's disease.

PMID- 16621168
TI  - Age-related changes in brain activation during a delayed item recognition task.
AB  - To test competing models of age-related changes in brain functioning (capacity
      limitation, neural efficiency, compensatory reorganization, and
      dedifferentiation), young (n=40; mean age=25.1 years) and elderly (n=18; mean
      age=74.4 years) subjects performed a delayed item recognition task for visually
      presented letters with three set sizes (1, 3, or 6 letters) while being scanned
      with BOLD fMRI. Spatial patterns of brain activity corresponding to either the
      slope or y-intercept of fMRI signal with respect to set size during memory set
      encoding, retention delay, or probe stimulus presentation trial phases were
      compared between elder and young populations. Age effects on fMRI slope during
      encoding and on fMRI y-intercept during retention delay were consistent with
      neural inefficiency; age effects on fMRI slope during retention delay were
      consistent with dedifferentiation. None of the other fMRI signal components
      showed any detectable age effects. These results suggest that, even within the
      same task, the nature of brain activation changes with aging can vary based on
      cognitive process engaged.

PMID- 16621169
TI  - Effects of estrogen and progesterone on spatial memory consolidation in aged
      females.
AB  - Interpretation of data illustrating that estrogen, with or without progestin, is
      detrimental to memory in post-menopausal women is complicated by the fact that
      little is known about the effects of progestins on memory. The present study
      examined if estrogen, alone or with progesterone, affects spatial memory
      consolidation in ovariectomized aged female mice. Mice received eight training
      trials in a spatial Morris water maze followed immediately by injection of water
      soluble 17beta-estradiol (E(2); 0.2 mg/kg) or vehicle. Mice were re-tested 24 h
      later. All mice learned to find the platform on Day 1. On Day 2, the performance
      of control, but not E(2) mice, deteriorated, suggesting that E(2) enhanced memory
      for the platform location. In a second experiment, mice were injected with E(2)
      and 10 or 20 mg/kg water-soluble progesterone. The 10 mg/kg dose of progesterone
      did not affect estrogen's ability to enhance spatial memory consolidation, but 20
      mg/kg blocked this effect. These data indicate that estrogen can improve spatial
      memory consolidation in aged females and that this effect can be attenuated by
      progesterone.

PMID- 16621170
TI  - Efficacy of MEM 1003, a novel calcium channel blocker, in delay and trace
      eyeblink conditioning in older rabbits.
AB  - Eyeblink conditioning is a relatively simple form of associative learning that
      shows neurobiological and behavioral parallels across several species, including
      humans. Aged subjects acquire eyeblink conditioning more slowly than young ones.
      In addition, eyeblink conditioning effectively discriminates patients with
      Alzheimer's disease from healthy older adults. The present study evaluated the
      effect of a novel L-type Ca2+ channel antagonist, MEM 1003, on delay and trace
      eyeblink conditioning in older (mean 33.4 months old) female New Zealand white
      rabbits. In the delay conditioning paradigm, an 850 ms tone conditioning stimulus
      (CS) was followed 750 ms after its onset by a 100 ms corneal air puff. Several
      trace conditioning paradigms were evaluated, with a silent period of 300, 400 or
      500 ms between the end of the tone CS and the delivery of the air puff. Learning
      was more difficult in the longer trace paradigms than in the delay paradigm. MEM
      1003, at a dose of 2.0 mg/kg, s.c., given daily 30 min prior to training on each
      of the 15 training days, enhanced learning compared to vehicle injections in both
      delay and trace paradigms. However, higher or lower doses were ineffective. These
      results support previous work demonstrating that modulation of Ca2+ channel
      activity can reduce age-related cognitive impairments.

PMID- 16621171
TI  - Chlamydia pneumoniae infection of brain cells: an in vitro study.
AB  - Inspired by the suggested associations between neurological diseases and
      infections, we determined the susceptibility of brain cells to Chlamydia
      pneumoniae (Cpn). Murine astrocyte (C8D1A), neuronal (NB41A3) and microglial (BV
      2) cell lines were inoculated with Cpn. Infection was established by
      immunofluorescence and real-time PCR at various time points. Productive infection
      was assessed by transferring medium of infected cells to a detection layer.
      Finally, apoptosis and necrosis post-infection was determined. Our data
      demonstrate that the neuronal cell line is highly sensitive to Cpn, produces
      viable progeny and is prone to die after infection by necrosis. Cpn tropism was
      similar in an astrocyte cell line, apart from the higher production of
      extracellular Cpn and less pronounced necrosis. In contrast, the microglial cell
      line is highly resistant to Cpn as the immunohistochemical signs almost
      completely disappeared after 24 h. Nevertheless, significant Cpn DNA amounts
      could be detected, suggesting Cpn persistence. Low viable progeny and hardly any
      necrotic microglial cells were observed. Further research is warranted to
      determine whether these cell types show the same sensitivity to Cpn in an in vivo
      setting.

PMID- 16621172
TI  - Influenza vaccination among cardiovascular disease sufferers in Spain: related
      factors and trend, 1993-2003.
AB  - Based on data drawn from the 1993 and 2003 National Health Surveys (NHS), we
      sought to: estimate influenza vaccination coverages among Spanish cardiovascular
      disease (CVD) sufferers; study which variables were associated with the
      likelihood of being vaccinated; analyze the time-trend in coverage for the period
      1993-2003. For study purposes, a CVD sufferer was defined as any adult who
      reported suffering from high blood pressure and/or heart disease. The proportion
      of vaccinated adult CVD sufferers in 1993 and 2003 totalled 39.96% and 51.73%,
      respectively. The following variables increased the likelihood of being
      vaccinated: higher age; male gender; presence of respiratory chronic diseases;
      non-smoker status. Coverages for CVD sufferers had improved significantly from
      1993 to 2003 but still remain below desirable levels. The improvement over time
      is mainly due to the subgroup aged >64 years. Strategies must be implemented to
      improve the use of influenza vaccine among CVD sufferers in Spain in general, and
      among the younger age-groups in particular.

PMID- 16621173
TI  - Intranasal immunization of mice with recombinant lipidated P2086 protein reduces
      nasal colonization of group B Neisseria meningitidis.
AB  - Neisseria meningitidis is a major cause of bacterial meningitis in the human
      population, especially among young children. There is a need to develop a non
      capsular vaccine to prevent meningococcal B infections due to the inadequate
      immune response elicited against the capsular polysaccharide of these strains.
      Previously, we developed a Swiss Webster adult mouse intranasal challenge model
      for group B N. meningitidis and evaluated several potential vaccine candidates
      including a meningococcal outer membrane protein, P2086, through parenteral
      immunization. Since N. meningitidis is a respiratory pathogen, a mucosal immune
      response may play an important role in the defense against meningococcal
      infections. Thus, intranasal immunization may be more effective than traditional
      parenteral immunization. In this study, mice were immunized intranasally with
      purified recombinant lipidated P2086 protein (rLP2086) adjuvanted with either CT
      E29H, a genetically modified cholera toxin that is significantly reduced in
      enzymatic activity and toxicity or RC529-AF, a synthetic immunostimulant molecule
      in aqueous formulation. rLP2086-specific serum and mucosal IgG and IgA antibodies
      were induced. IgG antibodies reacted with whole cells of multiple strains of
      group B N.meningitidis. The antibodies have functional activity against N.
      meningitidis as demonstrated by bactericidal assays. Moreover, immunized mice
      exhibited reduced nasal colonization of group B meningococcal strains in the
      intranasal challenge model. These results demonstrate that an intranasal
      immunization with rLP2086 protein formulated with a detoxified cholera toxin or
      RC529-AF could prevent the initial colonization of group B meningococcus and
      become an effective immunization strategy against group B N. meningitidis.

PMID- 16621174
TI  - Optimisation of the inactivated vaccine dose against heartwater and in vitro
      quantification of Ehrlichia ruminantium challenge material.
AB  - The aim of this work was to evaluate the minimal protective dose of the
      inactivated vaccine against heartwater. In order to conduct a reliable
      vaccination trial, an in vitro quantification method of Ehrlichia ruminantium
      (ER) challenge doses was developed. In experimental conditions, homologous Gardel
      challenges with 2.1 x 10(4) to 9.4 x 10(4) live ER elementary bodies were
      reproducible and mimicked a natural challenge. Similar results were obtained when
      animals were challenged with 3 x 10(4) live elementary bodies from five different
      ER strains. A 28-fold reduction of the vaccine dose did not decrease protection
      when compared to the conventional dose of inactivated vaccine. Two injections of
      35 microg of ER antigen induced good protection against heartwater. Moreover, we
      found that the amount of IFNgamma secreted in blood from vaccinated animals after
      in vitro stimulation with ER antigen was not a reliable predictor of survival and
      could not be used to test the potency of the inactivated vaccine.

PMID- 16621175
TI  - "Immunopotentiators in Modern Vaccines" (IMV-II) held in Malaga, Spain, May 18
      20, 2005.

PMID- 16621176
TI  - Helicobacter pylori lipopolysaccharide promotes a Th1 type immune response in
      immunized mice.
AB  - Helicobacter pylori (H. pylori) infection is prevalent worldwide and results in
      chronic gastritis, which may lead to peptic ulcer disease or gastric cancer. The
      goal of this study was to determine the role that H. pylori lipopolysaccharide
      (LPS) plays in stimulating host immune responses in the context of a vaccine. We
      compared H. pylori SS1 sonicate (LPS+) to a sonicate depleted of LPS (LPS-) in
      immunized BALB/c mice. Naive splenocytes produced high levels of TNF-alpha and IL
      10 after incubation with LPS+ sonicate, while cells incubated with LPS- sonicate
      did not. Mice immunized with LPS+ sonicate developed a prominent innate response
      characterized by increased TNF-alpha and IL-10, as well as a strong antigen
      specific Th1 response including, IFN-gamma, IL-2 and high IgG2a serum titers.
      Mice that received LPS- sonicate were strongly Th2 biased in their immune
      response, with significantly more IL-4 than IFN-gamma and serum IgG1 titers
      higher than IgG2a. Together these studies suggest that H. pylori LPS in a whole
      cell sonicate vaccine promotes a Th1 immune response that may aid in protection
      or clearance of H. pylori infection.

PMID- 16621177
TI  - Influenza vaccination coverage among children with high-risk medical conditions.
AB  - We evaluated influenza vaccination coverage in children with chronic disease at
      high risk of influenza complications, and the need for methods to increase
      parents' and pediatricians' knowledge of influenza and its prevention. The 5286
      children aged less than 14 years attending our Emergency Department on Wednesdays
      and Sundays between 1 January and 30 April 2003 included 274 (5.2%) high-risk
      patients. The use of influenza vaccine during the previous three seasons had been
      very low, but significantly increased in the last season (2000-2001, 5.1%; 2001
      2002, 12.9%; 2002-2003, 26.3%; p<0.001). The children with asthma or cardiac
      disease showed the lowest vaccination rates; their parents and primary care
      pediatricians had only a marginal knowledge of influenza and the benefits of its
      prevention. In conclusion, the delivery of influenza vaccine to children with
      chronic disease at high risk of influenza complications is completely inadequate,
      and major efforts are urgently needed to increase parents' and pediatricians'
      knowledge of its importance.

PMID- 16621178
TI  - Oral delivery of replication-competent adenovirus vectors is well tolerated by
      SIV- and SHIV-infected rhesus macaques.
AB  - Although replication-competent adenovirus (Ad) vectors are promising in AIDS
      vaccine design, their safety in immune compromised hosts is unknown. To initially
      address this question, enteric-coated tablets containing a replicating Ad vector
      were orally administered to SHIV- and SIV-infected rhesus macaques with normal,
      intermediate or low CD4 T cell counts and stable disease. The vector was detected
      within a week after tablet administration in stools of all animals but not in
      nasal secretions, indicating no spread of virus to the upper respiratory tract.
      CD4 T cell counts and viral loads remained stable in all animals and no signs of
      fever, weight loss, or other clinical symptoms of Ad-induced disease were
      observed during 10 weeks of follow-up. Oral delivery of the replicating Ad vector
      was safe and well tolerated by SHIV- and SIV-infected hosts. Oral enteric-coated
      tablets may prove safe for administering replicating Ad-vectored vaccines in
      areas with high HIV prevalence.

PMID- 16621179
TI  - Efficacy of vaccination with a combination of Leishmania amastigote antigens and
      the lipid A-analogue ONO-4007 for immunoprophylaxis and immunotherapy against
      Leishmania amazonensis infection in a murine model of New World cutaneous
      leishmaniasis.
AB  - Activation of innate immunity using adjuvants that activate Toll-like receptor 4
      pathways have great potential for improving the protection induced by parasite
      vaccines. We investigated protective and therapeutic effects of a vaccine against
      leishmaniasis containing a combination of an adjuvant synthetic lipid A-analogue,
      ONO-4007 and Leishmania amazonensis antigens. ONO-4007 was co-injected with
      soluble and membrane-enriched L. amazonensis-amastigote antigens into BALB/c mice
      that had either already been infected with 1 x 10(6) L. amazonensis promastigotes
      (immunotherapy study) or before challenge with the same infectious dose
      (immunoprophylaxis study). Sixty percent of mice vaccinated before infectious
      challenge controlled their Leishmania infections - defined by the absence of
      footpad-swelling and negative Leishmania cultures - compared to 0% of controls,
      and 40% of mice vaccinated after infection resolved their infections compared to
      0% of controls. Protective immunity in both immunoprophylaxis and immunotherapy
      models was associated with increased protein production of IL-12 and IFN-gamma.
      These data suggest that vaccination with a combination of ONO-4007 and amastigote
      antigens of L. amazonensis may be useful for the prevention and treatment of
      leishmaniasis, and that the protective immunity induced is associated with the
      production of type-1 cytokines.

PMID- 16621180
TI  - Interfering vaccine (defective interfering influenza A virus) protects ferrets
      from influenza, and allows them to develop solid immunity to reinfection.
AB  - Defective interfering (DI) virus RNAs result from major deletions in full-length
      viral RNAs that occur spontaneously during de novo RNA synthesis. These RNAs are
      packaged into virions that are by definition non-infectious, and are delivered to
      cells normally targeted by the virion. DI RNAs can only replicate with the aid of
      a coinfecting infectious helper virus, but the small size of DI RNA allows more
      copies of it to be made than of its full-length counterpart, so the cell produces
      defective virions in place of infectious progeny. In line with this scenario, the
      expected lethal disease in an influenza A virus-mouse model is made subclinical
      by administration of DI virus, but animals develop solid immunity to the
      infecting virus. Hence DI virus has been called an 'interfering vaccine'. Because
      interfering vaccine acts intracellularly and at a molecular level, it should be
      effective against all influenza A viruses regardless of subtype. Here we have
      used the ferret, widely acknowledged as the best model for human influenza. We
      show that an interfering vaccine with defective RNAs from an H3N8 virus almost
      completely abolished clinical disease caused by A/Sydney/5/97 (H3N2), with
      abrogation of fever and significant reductions in clinical signs of illness.
      Animals recovered fully and were solidly immune to reinfection, in line with the
      view that treatment converts the otherwise virulent disease into a subclinical
      and immunizing infection.

PMID- 16621181
TI  - Immunogenicity of the candidate malaria vaccines FP9 and modified vaccinia virus
      Ankara encoding the pre-erythrocytic antigen ME-TRAP in 1-6 year old children in
      a malaria endemic area.
AB  - In a phase 1 trial, 22 children in a malaria endemic area were immunised with
      candidate malaria vaccination regimes. The regimes used two recombinant viral
      vectors, attenuated fowlpox strain FP9 and modified vaccinia virus Ankara (MVA).
      Both encoded the pre-erythrocytic malaria antigen construct ME-TRAP. Strong T
      cell responses were detected by both ex vivo and cultured ELISpot assays. Data
      from phase 1 trials in adults on anti-vector responses raised by FP9 is
      presented. These responses partially cross-reacted with MVA, and detectably
      reduced the immunogenicity of vaccination with MVA. This prompted the comparison
      of half dose and full dose FP9 priming vaccinations in children. Regimes using
      half dose FP9 priming tended to be more immunogenic than full dose. The potential
      for enhanced immunogenicity with half doses of priming vectors warrants further
      investigation, and larger studies to determine protection against malaria in
      children are required.

PMID- 16621182
TI  - Age-specific changes in the female-male mortality ratio related to the pattern of
      vaccinations: an observational study from rural Gambia.
AB  - BACKGROUND: According to studies from Guinea-Bissau and Senegal, live vaccines
      may reduce the female-male mortality ratio (MR) whereas inactivated vaccines
      increase this ratio. We used data from The Gambia to examine whether similar
      tendencies could be found in a different setting. SETTING: Forty villages in the
      Farafenni area in rural Gambia. SUBJECTS: A population of 17,000 was followed
      with demographic surveillance between 1998 and 2002; 537 children less than 5
      years of age died in this period. METHODS: We used two vaccination surveys and
      community mortality data to examine, first, the female-male mortality ratio (MR)
      in the age groups in which DTP and MV are recommended and have a high coverage.
      Second, using vaccination cards seen post-mortem, we examined the distribution of
      live or inactivated vaccines as last vaccination in different age groups. Third,
      we examined the effect of DTP and MV administered simultaneously. MAIN OUTCOME
      MEASURES: The female-male MR in different age groups and for different vaccines.
      RESULTS: Vaccination coverage was high for BCG, third dose of DTP (DTP3) and MV,
      reaching a level of 80-90% within a few months of the recommended age of
      vaccination. First, the female-male MR was 0.93 (0.63-1.38) in the first 2 months
      of life when children had received no vaccination or the combination of BCG, HBV
      and OPV. From 2 to 8 months of age, with DTP and HBV being the main vaccinations,
      the female-male MR was 1.28 (0.86-1.89). Between 9 and 17 months of age, with MV
      as the main vaccination, this ratio dropped to 0.73 (0.50-1.07), a significant
      inversion of the female-male MR (p=0.045). Second, using information from
      vaccination cards of dead children, boys who died at 2-4 months of age were more
      likely to have received live BCG and girls to have received inactivated DTP and
      HBV as last vaccination (p<0.001). At 5-8 months of age, essentially all dead
      children had received DTP as last vaccination and the female-male MR was 1.68
      (0.96-2.93), whereas the MR was 0.70 (0.43-1.15) at 12-17 months of age when
      nearly all dead children had received MV (p=0.022). Third, compared with the
      general population of children who had received MV, dead children who had
      received MV were more likely to have received DTP3 simultaneously with MV
      (relative risk (RR)=5.59 (2.10-14.8)) or after MV (RR=2.61 (1.13-6.05)).
      CONCLUSION: Most children dying at a specific age had received the recommended
      vaccines. BCG and MV as last vaccination was associated with a low female-male
      MR, whereas DTP as last vaccination was associated with a high female-male MR.
      These trends are consistent with observations from other African countries.

PMID- 16621183
TI  - 4-1BB ligand enhances tumor-specific immunity of poxvirus vaccines.
AB  - PURPOSE: Recombinant poxvirus vaccines have been explored as tumor vaccines. The
      immunogenicity of these vaccines can be enhanced by co-expressing costimulatory
      molecules and tumor-associated antigens. While the B7-CD28 interaction has been
      most comprehensively investigated, other costimulatory molecules utilize
      different signaling pathways and might provide further cooperation in T cell
      priming and survival. 4-1BB (CD137) is a TNF family member and is critical for
      activation and long-term maintenance of primed T cells. This study was conducted
      to determine if a poxvirus expressing the ligand for 4-1BB (4-1BBL) could further
      improve the immune and therapeutic responses of a previously reported poxvirus
      vaccine expressing a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3).
      EXPERIMENTAL DESIGN: A recombinant vaccinia virus expressing 4-1BBL was generated
      and characterized in an in vitro infection system. This vaccine was then used
      alone or in combination with a vaccinia virus expressing CEA, B7.1, ICAM-1, and
      LFA-3 in CEA-transgenic mice bearing established MC38 tumors. Tumor growth and
      immune responses against CEA and other tumor-associated antigens were determined.
      The level of anti-apoptotic proteins in responding T cells was determined by flow
      cytometry on tetramer selected T cells. RESULTS: The combination of 4-1BBL with
      B7.1-based poxvirus vaccination resulted in significantly enhanced therapeutic
      effects against CEA-expressing tumors in a CEA-transgenic mouse model. This was
      associated with an increased level of CEA-specific CD4(+) and CD8(+) T cell
      responses, induction of antigen spreading to p53 and gp70, increased accumulation
      of CEA-specific T cells in the tumor microenvironment, and increased expression
      of bcl-X(L) and bcl-2 in CD4(+) and CD8(+) T cells in vaccinated mice.
      CONCLUSION: 4-1BBL cooperates with B7 in enhancing anti-tumor and immunologic
      responses in a recombinant poxvirus vaccine model. The inclusion of costimulatory
      molecules targeting distinct T cell signaling pathways provides a mechanism for
      enhancing the therapeutic effectiveness of tumor vaccines.

PMID- 16621184
TI  - In ovo DNA immunisation followed by a recombinant fowlpox boost is fully
      protective to challenge with virulent IBDV.
AB  - The aim of this study was to investigate the potential use of DNA vaccination
      delivered in ovo for protecting against challenge with infectious bursal disease
      virus (IBDV). Using a plasmid expressing the beta-galactosidase gene, DNA was
      successfully delivered to the embryo after in ovo injection and localises to the
      proventriculus and thymus. The coding sequence for the immunogenic IBDV protein,
      VP2, was cloned into pCI-neo, creating pCI-Vp2. Complete protection against IBDV
      was obtained by priming in ovo with pCI-Vp2, followed by boosting with the
      fowlpox recombinant, fpIBD1, also expressing the VP2 gene. This complete
      protection was not evident with either of the experimental vaccines on their own.
      An antibody response was not detected after the prime-boost vaccination, even
      after chicks had been challenged with IBDV, implying that the DNA prime delivered
      in ovo stimulated a protective cellular immune response.

PMID- 16621185
TI  - Humoral immune responses by prime-boost heterologous route immunizations with CTB
      MPR(649-684), a mucosal subunit HIV/AIDS vaccine candidate.
AB  - CTB-MPR(649-684) is a translational fusion protein consisting of the cholera
      toxin B subunit and a 36-residue peptide, MPR(649-684), corresponding to the
      conserved membrane proximal ectodomain of gp41. CTB-MPR(649-684) was previously
      shown to induce HIV-1 transcytosis-blocking antibodies in mice. In this report,
      we describe an effective immunization regimen for this novel anti HIV-1 vaccine
      candidate. Bacterially-produced CTB-MPR(649-684) was intranasally and/or
      intraperitoneally administered to investigate several prime-boost heterologous
      route immunization regimens. Mucosal priming with the adjuvant cholera toxin
      elicited significant levels of vaginal IgA and serum IgG specific to MPR(649
      684). Systemic boosting after mucosal priming enhanced the levels of serum and
      mucosal antibodies. Systemic priming induced a strong serum anti-MPR(649-684) IgG
      response, which was efficiently recalled and augmented by either systemic or
      mucosal boosting. However, this regimen was less effective in inducing secretory
      anti-MPR(649-684) IgA. The serum anti-MPR(649-684) IgG subtype profile revealed
      that both IgG1 and IgG2a were induced in all the immunization regimens, and that
      mucosal co-administration of cholera toxin shifted the bias to the latter
      subtype. We concluded that, of the various immunization regimens examined here,
      mucosal priming with adjuvant followed by systemic boosting exhibited the best
      response in respect to either systemic or mucosal anti-MPR(649-684) antibodies.
      Most importantly, mucosal antibodies elicited by this regimen significantly
      inhibited HIV-1 transcytosis in a human tight epithelium model.

PMID- 16621186
TI  - Interchangeability of Hepatitis A boosters, Avaxim and Vaqta, in healthy adults
      following a primary dose of the combined typhoid/Hepatitis A vaccine Viatim.
AB  - This study investigated the suitability of Avaxim and Vaqta as Hepatitis A
      booster vaccines 6 months after priming with the combined Hepatitis A/typhoid
      vaccine, Viatim. One hundred and twenty adults were randomly assigned to one of
      the three groups. Group A (reference group) received Avaxim then Avaxim (n = 40),
      Group B received Viatim then Avaxim (n = 41) and Group C received Viatim then
      Vaqta (n = 39). One month after booster vaccination, anti-Hepatitis A virus (anti
      HAV) antibodies geometric mean concentrations (GMC) of subjects primed with
      Viatim were non-inferior to the group primed and boosted with the monovalent
      Hepatitis A vaccine Avaxim. Anti-Salmonella typhi capsular polysaccharide
      virulence antigen (anti-Vi) GMCs in groups primed with Viatim were protective and
      all vaccines were well-tolerated. Therefore, Viatim may be used as a primary HAV
      vaccine with either Avaxim or Vaqta as Hepatitis A boosters and it will provide
      the same protection as two doses of Avaxim.

PMID- 16621187
TI  - The cost of influenza in Thailand.
AB  - The cost of influenza in less wealthy tropical countries is needed to inform
      national vaccine policy decisions. Between September 2003 and August 2004, we
      prospectively identified hospitalized pneumonia cases and outpatients with
      laboratory confirmed influenza in a Thai province. Disease incidence, patient
      interviews, medical record reviews, and data from a national health survey were
      used to calculate direct and indirect costs which were extrapolated to the Thai
      population. Influenza was identified in 80 (11%) of 761 hospitalized pneumonia
      inpatients with projected annual incidence of 18-111/100,000 population.
      Influenza was confirmed in 23% of 1092 outpatients with an estimated annual
      incidence of 1420/100,000 population. Influenza was estimated to cause between US
      dollar 23.4 and US dollar 62.9 million in economic losses with lost productivity
      accounting for 56% of all costs. The burden of influenza in Thailand is greater
      than previously appreciated, particularly in young children and the elderly. The
      impact and cost-effectiveness of influenza vaccination for high-risk groups
      merits further investigation.

PMID- 16621188
TI  - Immunization with SARS-CoV S DNA vaccine generates memory CD4+ and CD8+ T cell
      immune responses.
AB  - An effective vaccine for severe acute respiratory syndrome (SARS) will probably
      require the generation and maintenance of both humoral and cellular immune
      responses. It has been reported that after natural infection in humans and
      immunization in animals with SARS-CoV vaccine, antibody is produced and
      persistent for a long period of time. In the present study, mice were immunized
      i.m. with SARS-CoV S DNA vaccine, and three different methods (ELISA, ELISPOT and
      FACS) were used to evaluate the immune responses when the cells were stimulated
      in vitro with a pool of peptides overlapping entire SARS spike protein. The
      results show that prime-immunization with SARS-CoV S DNA vaccine can induce both
      CD4(+) and CD8(+) T cell responses. Boosting with the same vaccine enhances
      CD4(+) and CD8(+) T cell responses in both lymphoid and nonlymphoid organs and
      were persistent over two months. The SARS-CoV S-specific CD4(+) and CD8(+) T
      cells were CD62L(-), a marker for memory cells, and -30 to 50% of the cells
      expressed IL-7Ralpha (CD127), a marker for the capacity of effector cells to
      develop into memory cells. In addition, immunization with the DNA vaccine
      elicited high levels of antibody production. Taken together, these data
      demonstrate that immunization with SARS-CoV S DNA vaccine can generate antigen
      specific humoral and cellular immune responses that may contribute to long-term
      protection.

PMID- 16621189
TI  - A review of vaccine research and development: meningococcal disease.
AB  - This paper reviews the current status of research and development of vaccines
      against meningococcal disease due to Neisseria meningitidis, a major cause of
      severe meningitis and septicemia with epidemic potential. While five serogroups
      (A, B, C, Y, and W135) are responsible for most of the disease, Group A remains
      unique in its ability to cause large scale epidemics mainly in Africa but also in
      Asia. The majority of cases in Europe and America are due to Groups B and C. The
      successful experience with Hib and pneumococcal conjugate vaccines has paved the
      way for the development of polysaccharide conjugate vaccines for the prevention
      of meningococcal disease. Widespread vaccination with Group C conjugate vaccines
      now in use in several European countries indicates that these vaccines are
      immunogenic, induce immunological memory, reduce colonization and provide herd
      immunity to the general population. A monovalent group A conjugate vaccine being
      developed at an affordable price, offers hope for the elimination of large
      epidemics in African countries. Multivalent (A, C, Y, W) conjugate vaccines are
      being developed, and one has already been licensed. However, effective global
      prevention of meningococcal disease will not be achievable without the
      development of a vaccine against Group B meningitis, for which outer membrane
      protein vaccines are under development.

PMID- 16621190
TI  - Transcutaneous vaccination with virus-like particles.
AB  - Virus-like particles (VLP) are inert, empty capsids of viruses, which contain no
      DNA/RNA from the virus itself. However they retain the structure of a virus and
      they can be engineered to have antigens attached. We have constructed VLP,
      derived from Rabbit hemorrhagic disease virus, and shown they are highly
      immunogenic. We tested the capacity of these engineered VLP to induce immune
      responses when they are administered to mice via the transcutaneous route. This
      route of vaccination is important, in order to generate mucosal protection. Our
      data showed that VLP are taken up by dendritic cells (DC), antigen-presenting
      cells that are essential to initiate acquired immune responses. The VLP induced
      an increase in expression of CD40, CD80 and CD86 but required an adjuvant, CpG
      DNA oligo-deoxy nucleotides (ODN) motifs, to enhance these responses. In vivo
      testing has also shown that the VLP, when wiped on to the skin in conjunction
      with immunostimulatory CpG, induce Ag-specific immune responses, typified by high
      levels of IFN-gamma and IgG1.

PMID- 16621191
TI  - Pro-apoptotic DNA vaccination ameliorates new onset of autoimmune diabetes in NOD
      mice and induces foxp3+ regulatory T cells in vitro.
AB  - We have shown previously that incorporation of a cDNA coding for the pro
      apoptotic protein BAX into plasmid DNA coding for a secreted form of the
      pancreatic beta-cell antigen glutamic acid decarboxylase (GAD) promotes
      prevention of type 1 diabetes in non-obese diabetic (NOD) mice. Here we present
      evidence indicating that injection of the same vaccine at time of early diabetes
      onset could ameliorate the disease with efficacy, with 42% of mice overtly
      diabetic by 40 weeks of age compared to 92% in control groups. In addition,
      immunological analysis revealed that the DNA vaccine induced CD4(+)CD25(+) T
      cells cultured from draining lymph nodes that had immunosuppressive function in
      vitro. The induced regulatory T cells (Tregs) expressed the foxp3 gene and showed
      cell-contact-dependent as well as TGF-beta- and IL-10-independent
      immunosuppressive activity. Data also revealed that CD4(+)CD25(-) T cells from
      mice immunized with the DNA vaccine yielded a cell population that was foxp3(+),
      showed increased expression of CD25 compared to control, and had
      immunosuppressive function in vitro, indicating that Tregs could have developed
      from antigen-induced, peripheral T lymphocytes. In contrast, injection of DNA
      coding for SGAD55 or BAX alone did not induce Tregs. Altogether, our data confirm
      that pro-apoptotic DNA vaccination can be used as an immunosuppressive strategy
      and demonstrate its potential for therapy of pathological autoimmunity.

PMID- 16621192
TI  - A soluble LAG-3 protein as an immunopotentiator for therapeutic vaccines:
      Preclinical evaluation of IMP321.
AB  - A soluble LAG-3 (CD223) molecule (sLAG-3) is a natural high affinity ligand for
      MHC class II. It is known to induce maturation of monocyte-derived dendritic
      cells in vitro and is used as a vaccine adjuvant to induce CD4 Th1 and CD8 T cell
      responses in vivo. The work presented herein was performed to study the
      biological activity of a preclinical grade human sLAG-3 protein, called IMP321:
      (i) binding on murine APC, (ii) induction of dendritic cell maturation, (iii)
      safety of repeated injections in mice. The results show that IMP321 binds MHC
      class II(+) murine APC, induces the maturation of dendritic cells and is well
      tolerated either injected alone or as an adjuvant with strongly immunogenic
      antigens.

PMID- 16621193
TI  - HIV-1 Envgp140 trimers elicit neutralizing antibodies without efficient induction
      of conformational antibodies.
AB  - Currently, no vaccine for human immunodeficiency virus (HIV-1) provides
      protection from virus infection. One reason for these disappointing results has
      been the difficulty of current vaccine candidates to elicit high-titer, broadly
      reactive immunity to a large number of viral proteins. Recently, our laboratory
      demonstrated that the coupling of C3d to a soluble trimerized HIV-1 envelope
      (Env(gp140(FT))) elicited higher titers of neutralizing antibodies than monomers
      of Env(gp120) coupled to C3d [Bower JF, Yang X, Sodroski J, Ross TM. Elicitation
      of neutralizing antibodies with DNA vaccines expressing soluble stabilized human
      immunodeficiency virus type 1 envelope glycoprotein trimers conjugated to C3d. J
      Virol 2004;78(9):4710-9]. To determine if the induction of conformational
      antibodies correlated with neutralization, mice (BALB/c) were primed (2x) with
      DNA plasmids expressing monomeric Env(gp120) or trimeric Env(gp140) alone or
      fused to mC3d(3) at one of two doses (2.0microg or 0.2microg), followed by a
      boost of recombinant uncleaved, trimeric Env(gp140). Regardless of the priming
      dose of DNA, all mice had high-titer anti-Env IgG antibodies. Interestingly,
      Env(gp140) trimers did not elicit higher titers of antibodies that recognized
      conformational Env epitopes compared to monomers of Env(gp120). Therefore,
      additional parameters were examined for correlation with neutralization. For
      neutralization-resistant HIV-1 isolates, ADA and YU-2, neutralization correlated
      with high-titer, high avidity antibodies, with Env(gp140) eliciting slightly
      higher neutralization titers than Env(gp120). In contrast, none of the measured
      parameters correlated with neutralization for the more neutralization-sensitive
      isolates, MN or 89.6. Therefore, even though soluble, uncleaved Env(gp140)
      trimers may be marginally more effective at eliciting neutralizing antibodies
      than Env(gp120), neutralization does not appear to correlate with the elicitation
      of conformationally dependent antibodies.

PMID- 16621194
TI  - Effects of the potency and composition of the multivalent human-bovine (WC3)
      reassortant rotavirus vaccine on efficacy, safety and immunogenicity in healthy
      infants.
AB  - BACKGROUND: Rotavirus gastroenteritis, which causes substantial infant mortality
      and morbidity worldwide, is a vaccine-preventable disease. The purpose of this
      study was to evaluate different compositions and potencies (vaccine virus titers)
      of a live multivalent human-bovine (WC3) reassortant rotavirus vaccine in order
      to select the potency and composition of the vaccine for further development.
      METHODS: The efficacy, safety, and immunogenicity of a G1, G2, G3, G4, and P1A
      pentavalent composition at three different potencies, a G1, G2, G3, G4
      quadrivalent composition, and a P1A monovalent composition of an oral human
      bovine (WC3) reassortant rotavirus vaccine were compared in a blinded, placebo
      controlled trial conducted between 1998 and 2001 enrolling 1,946 healthy Finnish
      infants 2-8 months of age. RESULTS: All potencies of the pentavalent and
      quadrivalent vaccines were efficacious (58-74%) against wild-type rotavirus
      gastroenteritis of any severity and 100% protective against severe rotavirus
      disease caused by vaccine G-serotypes through the first rotavirus season post
      vaccination. The monovalent P1A vaccine was 53% efficacious against moderate-and
      severe rotavirus gastroenteritis. Protection against rotavirus gastroenteritis of
      any severity was demonstrated through two and three rotavirus seasons for all
      vaccine compositions. After the third dose, the percentage of infants with >or=3
      fold rise in baseline serum neutralizing antibody titers against G1 ranged from
      62% to 86% for recipients of the pentavalent vaccine, depending on the potency.
      The incidence of fever, irritability, vomiting, and diarrhea did not
      significantly differ between vaccine and placebo groups. A 7-month-old male
      developed intussusception 9 days after the first dose of the low-potency
      pentavalent vaccine. CONCLUSIONS: Based on the results of this trial, a
      pentavalent composition (G1, G2, G3, G4, and P1A) of human-bovine (WC3)
      reassortant rotavirus vaccine with a potency similar to that of the middle
      potency pentavalent vaccine ( approximately 8 x 10(6) plaque-forming units/dose)
      was selected for further development.

PMID- 16621195
TI  - A synthetic dengue virus antigen elicits enhanced antibody titers when linked to,
      but not mixed with, Mycobacterium tuberculosis HSP70 domain II.
AB  - Domain II of Mycobacterium tuberculosis (Mtb) heat shock protein 70 (HSP70),
      spanning amino acid residues 161-370, was covalently linked to a recently
      described synthetic dengue virus antigen to study the influence of the former on
      the immunogenicity of the latter. Using an enzyme-linked immunosorbent assay,
      dengue antigen-specific antibody titers elicited by the fusion protein in Balb/c
      mice were an order of magnitude higher than those elicited by either the
      synthetic dengue antigen alone or a physical mixture of the dengue antigen plus
      Mtb HSP70 domain II protein. Our data demonstrate that (i) Mtb HSP70 domain II is
      capable of potentiating B-cell response and (ii) it should be covalently linked
      to the target antigen to do so.

PMID- 16621196
TI  - Immunogenicity of Salmonella vector vaccines expressing SBR of Streptococcus
      mutans under the control of a T7-nirB (dual) promoter system.
AB  - The purpose of the present study was to determine if a Salmonella vector
      expressing the cloned saliva-binding region (SBR) of Streptococcus mutans or SBR
      linked to the A2 and B subunits of cholera toxin (CTA2/B) under the control of
      both the T7 and nirB promoters (T7-nirB dual promoter) was more effective in
      inducing mucosal and systemic anti-SBR antibody responses than Salmonella clones
      expressing the same antigens but under the control of either the nirB or T7
      promoter. Mice were immunized by the intranasal route on days 0, 18 and 320 with
      Salmonella enterica serovar Typhimurium strain BRD 509 containing one of six
      plasmids encoding SBR or SBR-CTA2/B under the control of the T7-nirB, T7, or nirB
      promoter. Serum, saliva and vaginal wash samples were collected throughout the
      experiment and assessed for antibody activity by ELISA. Evidence is provided that
      Salmonella clones expressing SBR or SBR-CAT2/B under the control of either the T7
      or T7-nirB promoter induced a high and persistent mucosal and systemic anti-SBR
      antibody response. All Salmonella clones induced good anti-SBR responses
      following the boost on day 320.

PMID- 16621197
TI  - Identification of two subpopulations of Bacillus Calmette-Guerin (BCG) Tokyo172
      substrain with different RD16 regions.
AB  - Two types of colonies with different morphologies (smooth: S and rough: R) formed
      when Bacillus Calmette-Guerin (BCG) Tokyo172 substrain was cultured on
      Middlebrook 7H10 agar medium, and their genotypes were analyzed by multiplex PCR
      on five RD regions and SenX3-RegX3. In most cases these two colony types had
      different genotypes, i.e., S colonies showed a characteristic 22 bp deletion in
      Rv3405c of the RD16 region (type I), and R colonies did not have this deletion
      (type II) similar to many other BCG substrains. Thus, there was a strong
      relationship between colony morphology and genotype. Both genotypes were found in
      every Tokyo172 preparation tested, including the seed lot for production, the
      origin of seed lot from the 1960s and ATCC BCG Japan. Type I was always in the
      majority. It was suggested that types I and II constituted independent
      subpopulations within the Tokyo172 substrain. Type I was shown to have a growth
      advantage over type II both on culture media and in mice organs.

PMID- 16621198
TI  - Potent protective cellular immune responses generated by a DNA vaccine encoding
      HSV-2 ICP27 and the E. coli heat labile enterotoxin.
AB  - A mouse model was employed to evaluate protective cellular immune responses
      induced by an immediate early antigen of HSV-2. Particle-mediated DNA vaccination
      of mice with a DNA plasmid-encoding ICP27 resulted in the induction of ICP27
      specific IFN-gamma and TNF-alpha production in Balb/c mice, but little protection
      to intranasal challenge with wild type HSV-2. However, when the DNA vaccine was
      supplemented with as little as 50ng of a vector encoding the A and B subunits of
      the Escherichia coli heat labile enterotoxin (LT), animals were profoundly
      protected from morbidity and mortality. The ICP27+LT-mediated protection was
      correlated with a large increase in ICP27-specific IFN-gamma and TNF-alpha
      production but cytokine-specific monoclonal antibody treatment at the time of
      challenge showed that protection was mediated predominantly by IFN-gamma.
      Furthermore, depletion of T cell subsets prior to infectious challenge
      demonstrated that removal of either CD8+ or CD4+ T cells impaired protection with
      CD8+ T cells appearing to play a direct effector role. These data demonstrate
      that augmented cellular immune responses resulting from LT vector plus antigen
      vector administration to the skin are biologically significant, leading to
      enhanced protection against mucosal pathogenic challenge.

PMID- 16621199
TI  - Construction and immunogenicity of recombinant fowlpox vaccines coexpressing HA
      of AIV H5N1 and chicken IL18.
AB  - cDNAs of the HA genes of subtype H5N1 AIV were fused to form a single open
      reading frame, designated H5HA-H7HA. The H5HA-H7HA cDNA and chicken Interleukin
      18 (IL18) were inserted into the fowlpox virus (FPV) expression vector pUTA-16
      LacZ to produce pUTAL-H5-H7-IL18. cDNA of H5N1 AIV HA was inserted into the FPV
      expression vector pUTA2 to create the recombinant expression plasmid pUTA2-H5.
      Plasmids were then co-transected into CEF cells. The two recombinant fowlpox
      viruses (rFPV) were produced by three cycles with the BrdU and verified by RT
      PCR, IFA and Western blotting. One-day-old specific pathogen free (SPF) chickens
      and 7-day-old commercial Leghorn egg-laying chickens were inoculated with 10(6)
      PFU recombinant or parental fowlpox vaccine viruses by wing-web puncture.
      Hemagglutination inhibition (HI) antibody titer and nonspecific cellular immunity
      level were assessed after 1-3 weeks post-immunization. We found that all rFPV
      vaccinated groups produced HI-specific antibodies, and the level of cellular
      immunity induced by the rFPV-H5-H7-IL18 strain was significantly higher than that
      induced by rFPV-H5HA. At 3 weeks post-inoculation, immunized SPF and Leghorn
      chickens were challenged with H5N1 HP AIV. The rFPV-H5-H7-IL18 vaccine strains
      were able to induce complete (10/10) protection, while the rFPV-H5HA vaccine
      strain induced (9/10) protection. Cloacal swabbing samples were collected from
      immunized leghorn chickens during the first week post-challenge; no shedding was
      found in the rFPV-H5-H7-IL18 vaccinated group. The rFPV-H5-H7-IL18 vaccinated
      group displayed significantly increased weight gain relative to the rFPV-H5HA
      group. This study reports a significant step in the further development of new
      AIV vaccines.

PMID- 16621200
TI  - Phase II randomized, placebo-controlled trial of M. vaccae-derived protein (PVAC)
      for the treatment of psoriasis.
AB  - The treatment effect against psoriasis of an antigen (delipidated,
      deglycolipidated form of M. vaccae-PVAC) was investigated. One hundred and sixty
      five patients were enrolled in three arms (50 or 15 microg or placebo), each
      receiving a total of two intradermal injections (days 0 and 21). At week 12, a
      75% decrease in psoriasis area and severity index was similar among the studied
      groups (13, 9 and 18%, p=0.429). The overall incidence of adverse events was
      significantly higher in the PVAC treated groups when compared to placebo (98.2,
      87.3 and 70.9%; p<0.001) largely due to local reactions that were limited for the
      most part to grades 1 and 2 in severity and were self-limiting. Despite its
      overall safety, PVAC was not clearly indicated to be superior to placebo in the
      treatment of psoriasis in this study.

PMID- 16621201
TI  - Alpha radioactivity in drinking water in Quebec, Canada.
AB  - The median gross-alpha radioactivity found in 236 drinking water samples in
      Quebec was 52 mBq/l. Only 3% of samples studied have an activity higher than the
      Maximum Contaminant Level of 555 mBq/l. The median detection limit of the method
      described is 24 mBq/l.

PMID- 16621202
TI  - Simple aids to venotomy in microvascular reconstructive surgery in the head and
      neck.

PMID- 16621203
TI  - Gingival recession: rare but significant complication of the Le Fort I osteotomy.

PMID- 16621204
TI  - Benign paroxysmal positional vertigo: an unusual complication of molar teeth
      extraction.

PMID- 16621205
TI  - Distraction osteogenesis with subperiosteal devices in edentulous mandibles.

PMID- 16621206
TI  - Predictability of the fibular flap for the reconstruction of the condyle
      following mandibular ablation.

PMID- 16621207
TI  - A safe and accurate technique for transbuccal incisions.

PMID- 16621208
TI  - A simple method to hold the ramus retractor.

PMID- 16621209
TI  - The free fibular flap: a useful flap for reconstruction following composite hand
      injuries.
AB  - The free fibular flap has been used extensively in facial and extremity long bone
      reconstruction but has not been presented as a tool for reconstruction following
      composite hand injuries, in particular for reconstruction of the ulnar border of
      the hand. We present a case of the use of this flap for reconstruction of such a
      complex composite hand injury.

PMID- 16621211
TI  - Effect of acid rain on building material of the El Tajin archaeological zone in
      Veracruz, Mexico.
AB  - Three limestone slabs (approx. 20 cm2 each) were extracted from the El Tajin
      archaeological zone in Veracruz, Mexico. X-ray diffraction analysis revealed
      three components: calcite (81.2%), quartz (17.9%) and feldspar (0.9%). Calcite
      content by x-ray diffraction analysis was slightly higher than that determined by
      chemical reaction between the limestone sample and nitric acid. The latter
      analysis, carried out in triplicate, yielded a calcite content of 77.1%. Mean
      water absorption, density and porosity of the limestone samples were also
      determined. Dissolution of limestone samples was investigated using an
      experimental rainfall simulation chamber, in which the stone samples were
      irrigated with artificial rain matching the pH and the ionic composition with 40
      rainfall samples collected at El Tajin from August 18, 2002, to April 9, 2003.
      According to calcium and bicarbonate net concentrations found in the effluent of
      the chamber, a chemical mechanism by which limestone at El Tajin is dissolved by
      acid rain is proposed. A model used to investigate the air transport pathways
      corresponding to precipitation events at El Tajin shows that air parcels come
      mainly from the Gulf of Mexico, although no directional preference is evident for
      acidic vs. non-acidic events.

PMID- 16621210
TI  - Variability in isometric force and moment generating capacity of glenohumeral
      external rotator muscles.
AB  - BACKGROUND: Muscles which cause glenohumeral external rotation possess varying
      ability for generating force and moment due to differences in muscle
      architecture, moment arm, and the interaction of these two factors. This study's
      purpose was to determine a complete dataset of muscle-tendon parameters for
      predicting the moment generating capacity and force-length dependence for
      external rotation of infraspinatus, supraspinatus and teres minor muscles.
      METHODS: Muscle fascicle length, sarcomere length, pennation angle, and muscle
      volume were measured for sub-regions of infraspinatus and supraspinatus, and
      teres minor from 10 glenohumeral specimens. Tendon excursion was measured for
      glenohumeral rotation. From these parameter measurements, optimal fascicle
      length, physiological cross-sectional area, muscle force-length dependence, and
      maximum isometric moment generating capacity were calculated. FINDINGS:
      Substantial differences were found for optimal muscle length, physiologic cross
      sectional area, and tendon length for the 10 specimens of this study. Muscle sub
      region had a significant effect on the force-length relationship for
      infraspinatus (P<0.001), but was not significant for supraspinatus (P=0.49). For
      infraspinatus and supraspinatus, maximum isometric rotation moment capacity was
      greater at 10 degrees versus 60 degrees abduction (P<0.001). Maximum isometric
      rotation moment capacity for the teres minor was greater at 10 degrees versus 60
      degrees abduction (P<0.01). Sub-regions demonstrated significant differences in
      isometric moment capacity (P<0.001). INTERPRETATION: Functional capabilities of
      these muscles depend on muscle architecture and moment arm as well as their
      combined effects. The results allow for development of stochastic and
      deterministic models of glenohumeral external rotation strength which can be used
      for prediction of muscle forces and joint moments.

PMID- 16621212
TI  - Micronuclei and cell proliferation as early biological markers of ortho
      phenylphenol-induced changes in the bladder of male F344 rats.
AB  - ortho-Phenylphenol (OPP) and its sodium salt, sodium ortho-phenylphenate (SOPP),
      are widely used fungicides and antibacterial agents known to cause tumors in the
      bladders of male F344 rats. Previous studies in our laboratory have shown that
      micronuclei and cell proliferation were induced in the bladders of treated rats
      by a high dose of OPP. In our present studies, we investigated the relationship
      in dose response between these two biomarkers and previously reported tumor
      formation in the bladders of male F344 rats. Significant non-linear increases in
      micronuclei (MN) and BrdU-labeling were seen in the bladder cells of rats treated
      with the 8000 and 12,500 ppm doses of OPP and at 20,000 ppm SOPP. CREST anti
      kinetochore staining showed that the micronuclei originated from both chromosomal
      loss and breakage. In addition, increases in MN were detected in the bladder but
      not in the bone marrow, underscoring the value of assessing genotoxicity in the
      target organ. In summary, these studies clearly show that at high doses, OPP and
      SOPP are genotoxic to the rat bladder. These results also indicate that
      micronucleus formation and cell proliferation can detect early OPP-induced
      changes in the rat bladder and may be useful as biomarkers for bladder
      carcinogens.

PMID- 16621213
TI  - Effect of subchronic exposure to malathion on glycogen phosphorylase and
      hexokinase activities in rat liver using native PAGE.
AB  - The aim of this study was the evaluation of the effects of a subchronic exposure
      to malathion, an organophosphorus (OP) insecticide, on plasma glucose and hepatic
      enzymes of glycogenolysis and glycolysis in rats in vivo. Malathion was
      administered intragastrically by stomach tube in the amount of 1 ml corn oil
      containing 100mg/kg body weight (BW) daily for 32 days. At the end of the
      experiment, the liver was removed. The activities of glycogen phosphorylase (GP)
      and hexokinase (HK) were analysed in the homogenate. The methodology employed was
      a non-denaturing electrophoresis followed by activity-staining (native PAGE).
      Malathion decrease GP activity by 50% and increase HK activity by 10%. In
      addition, an hepatomegaly was recorded with a rise in the hepatic glycogen rate
      in malathion-treated rats. Moreover, subchronic administration of malathion has
      no effect on blood glucose concentration. The storage of glycogen in liver may be
      due to a stimulation of insulin secretion after the inhibition of
      acethylcholinesterase activity in pancreatic beta cells by malathion. These
      findings were in favour of an activation of glycogen storage by malathion.

PMID- 16621214
TI  - Ochratoxin A alters cell adhesion and gap junction intercellular communication in
      MDCK cells.
AB  - Ochratoxin A (OTA) is one of the most potent renal carcinogens studied to date,
      but the mechanism of tumor formation by ochratoxin A remains largely unknown.
      Cell adhesion and cell-cell communication participate in the regulation of
      signaling pathways involved in cell proliferation and growth control and it is
      therefore not surprising that modulation of cell-cell signaling has been
      implicated in cancer development. Several nephrotoxicants and renal carcinogens
      have been shown to alter cell-cell signaling by interference with gap junction
      intercell communication (GJIC) and/or cell adhesion, and the aim of this study
      was to determine if disruption of cell-cell interactions occurs in kidney
      epithelial cells in response to OTA treatment. MDCK cells were treated with OTA
      (0-50 microM) for up to 24h and gap junction function was analyzed using the
      scrape-load/dye transfer assay. In addition, expression and intracellular
      localization of C x 43, E-cadherin and beta-catenin were determined by immunoblot
      and immunofluorescence analysis. A clear decrease in the distance of dye transfer
      was evident following treatment with OTA at concentrations/incubation times which
      did not affect cell viability. Consistent with the functional inhibition of GJIC,
      treatment with OTA resulted in a dose-dependent decrease in C x 43 expression. In
      contrast to C x 43, OTA did not alter total amount of the adherens junction
      proteins E-cadherin and beta-catenin. Moreover, Western blot analysis of Triton X
      100 soluble and insoluble protein fractions did not indicate translocation of
      cell adhesion molecules from the membrane to the cytoplasm. However, a
      approximately 78 kDa fragment of beta-catenin was detected in the detergent
      soluble fraction, indicating proteolytic cleavage of beta-catenin.
      Immunofluorescence analysis also revealed changes in the pattern of both beta
      catenin and E-cadherin labeling, suggesting that OTA may alter cell-adhesion.
      Taken together, these data support the hypothesis that disruption of cell-cell
      signaling may contribute to OTA toxicity and carcinogenicity.

PMID- 16621215
TI  - Mitochondrial permeability transition as a potential determinant of
      hepatotoxicity of antidiabetic thiazolidinediones.
AB  - Troglitazone, a thiazolidinedione class of antidiabetic agent, causes serious
      idiosyncratic hepatotoxicity. Troglitazone is metabolized to a reactive
      metabolite that covalently binds to cellular macromolecules, but the role of the
      covalent adduct in the hepatotoxicity is controversial. Because troglitazone has
      been found to cause cytotoxicity to hepatocytes along with mitochondrial
      dysfunction, we investigated the effects of troglitazone and other
      thiazolidinediones on mitochondrial function by using liver mitochondria fraction
      isolated from male CD-1 mice. Incubation of energized mitochondria with succinate
      in the presence of Ca2+ and troglitazone induced mitochondrial swelling, and the
      swelling was partially inhibited by cyclosporin A. Troglitazone also induced
      decreases in mitochondrial membrane potential and mitochondrial Ca2+
      accumulation. These results demonstrate that troglitazone induces mitochondrial
      permeability transition (MPT). Similar results were obtained for ciglitazone,
      whereas rosiglitazone and pioglitazone, which are less hepatotoxic than
      troglitazone, had little effect on these mitochondria functions. It is therefore
      possible that the troglitazone-induced opening of MPT pore, which is not induced
      by rosiglitazone or pioglitazone, may contribute to the hepatotoxicity induced
      specifically by troglitazone.

PMID- 16621216
TI  - Smoking specifically induces metallothionein-2 isoform in human placenta at term.
AB  - Recently, we reported the presence of higher levels of metallothionein (MT) in
      placentas of smokers compared to non-smokers. In the present study, we designed
      experiments to separate and evaluate two isoforms of MT (MT-1 and MT-2) in
      placentas of smokers and non-smokers. Metallothionein was extracted and separated
      by ion-exchange high performance liquid chromatography (HPLC), previous
      saturation with cadmium chloride. Two peaks eluting at 6 and 12.5 min,
      corresponding to MT-1 and MT-2, respectively, were obtained. Metallothionein
      present in both peaks was identified by Western blot analysis using a monoclonal
      antibody directed against MT-1 and MT-2. Each isoform concentration was
      calculated after measuring its cadmium content by atomic absorption spectrometry
      with inductively coupled-plasma. In placentas of smokers, MT-2 levels increased
      by seven-fold compared to non-smokers, whereas MT-1 was not changed. Total
      placental cadmium and zinc concentrations, determined by atomic absorption
      spectrometry and neutron activation analysis, respectively, were higher in
      smokers. Metallothioneins levels were clearly in excess to bind all cadmium ions
      present in placentas. However, most of placental zinc remains unbound to MTs,
      although as much as twice zinc ions could be bound to MT in smokers. In
      conclusion, MT-2 is the main isoform induced by smoking, suggesting that this
      isoform could be involved in placental cadmium and zinc retention. This fact,
      which could contribute to reduce the transference of zinc to the fetus, may be
      associated to detrimental effects on fetal growth and development.

PMID- 16621217
TI  - Occupational exposure in airport personnel: characterization and evaluation of
      genotoxic and oxidative effects.
AB  - Airport personnel can be exposed to several polycyclic aromatic hydrocarbons
      (PAHs) from jet fuel vapours, jet fuel combustion products and diesel exhaust.
      The aim of this study was to characterize the exposure and to evaluate genotoxic
      and oxidative effects in airport personnel (n=41) in comparison with a selected
      control group (n=31). Environmental monitoring of exposure was carried out
      analysing 23 PAHs on air samples collected from airport apron, airport building
      and terminal/office area during 5 working days. The urinary 1-hydroxy-pyrene (1
      OHP) following 5 working days, was used as biomarker of exposure. Genotoxic
      effects and early direct-oxidative DNA damage were evaluated by micronucleus (MN)
      and Fpg-modified comet assay on lymphocytes and exfoliated buccal cells, and by
      chromosomal aberrations (CA) and sister chromatid exchange (SCE) analyses. For
      comet assay, tail moment (the product of comet relative tail intensity and
      length) values from Fpg-enzyme treated cells (TMenz) and from untreated cells
      (TM) were used as parameters of oxidative and direct DNA damage, respectively. We
      found 27,703 microg/m(3) total PAHs in airport apron, 17,275 microg/m(3) in
      airport building and 9,494 microg/m(3) in terminal/office area. Urinary OH-pyrene
      did not show differences between exposed and controls. The exposed group showed a
      higher mean value of SCE frequency in respect to controls (4.6 versus 3.8) and an
      increase (1.3-fold) of total structural CA in particular breaks (up to 2.0-fold)
      and fragments (0.32% versus 0.00%), whereas there were no differences of MN
      frequency in both cellular types. Comet assay evidenced in the exposed group a
      higher value in respect to controls of mean TM and TMenz in both exfoliated
      buccal cells (TM 118.87 versus 68.20, p=0.001; TMenz 146.11 versus 78.32,
      p<0.001) and lymphocytes (TM 43.01 versus 36.01, p=0.136; TMenz 55.86 versus
      43.98, p=0.003). An oxidative DNA damage was found, for exfoliated buccal cells
      in the 9.7% and for lymphocytes in the 14.6% of exposed in respect to the absence
      in controls. Our findings furnish a useful contribution to the characterization
      of civil airport exposure and suggest the use of comet assay on exfoliated buccal
      cells to assess the occupational exposure to mixtures of inhalable pollutants at
      low doses since these cells represent the target tissue for this exposure and are
      obtained by non-invasive procedure.

PMID- 16621218
TI  - The influence of cigarette smoking on human sperm quality and DNA fragmentation.
AB  - The aim of the present study was to evaluate consequences of cigarette smoking on
      male gametes. In this prospective study, sperm parameters such as sperm density,
      motility, viability and normal morphology were measured according to the WHO
      criteria. In addition to these standard parameters, we analysed the degree of DNA
      fragmentation in spermatozoa using the TUNEL-assay with flow cytometry detection
      in 57 non-smokers and 51 smokers seeking for infertility counselling. The smoking
      intoxication was assessed by questionnaire and measured with the CO-Tester. We
      show that smokers' spermatozoa have a significantly higher DNA fragmentation than
      non-smokers (32% versus 25.9%, p<0.01). In contrast there is no significant
      difference in conventional parameters between smokers and non-smokers. The degree
      of sperm DNA fragmentation is not significantly correlated with any of the
      conventional parameters. These findings suggest that cigarette smoking may have
      deleterious effects on sperm nuclear quality and that sperm DNA fragmentation can
      therefore be considered as an independent parameter with diagnostic, prognostic,
      and strategic value in the treatment of infertility.

PMID- 16621219
TI  - Conditioning effect on dentin, resin tags and hybrid layer of different acidity
      self-etch adhesives applied to thick and thin smear layer.
AB  - OBJECTIVES: to assess the conditioning effect (CE) of self-etch adhesives of
      different acidity applied to thick and thin smear layer (SL), the corresponding
      resin tags (RT) and hybrid layer (HL). METHODS: Twenty-seven molars had their
      occlusal dentin exposed and were sectioned into two halves. Each of them was
      ground with a 60 or 600-grit SiC paper, respectively for thick and thin SL
      production. Three self-etch adhesives: a mild (Clearfil SE Bond), an intermediary
      (Optibond Solo SE and Solo Plus) and a strong (Tyrian Self Priming Etchant+One
      Step Plus) and an etch-&-rinse system (Scotchbond Multi Purpose Plus) were used.
      For CE evaluation, the self-etch primers were applied and rinsed off with acetone
      and alcohol prior to SEM preparation. For RT and HL specimens self-etch adhesives
      were applied and restored with Z-250. For RT specimens, dentin was removed with
      HCl (6N) and NaClO (1%) baths. The HL specimens were fixed, dehydrated, dried
      with HMDS, embedded, polished and slightly demineralized (6N HCl) and
      deproteinized (1% NaClO). After gold sputtering they were observed by SEM.
      RESULTS: The thick smear layer was clearly not totally removed by the mild self
      etch primer. RT varied in density and shape among the self-etch adhesives.
      Thicker HL was observed for the strong self-etch and etch-&-rinse adhesives.
      CONCLUSIONS: The etch-&-rinse adhesive presented the thickest HL and was the only
      adhesive to produce RT in high density and uniform distribution along the whole
      dentin surface, independently of the SL thickness.

PMID- 16621221
TI  - External cardiac pacing causing Staphylococcus aureus septicaemia.

PMID- 16621222
TI  - How often is a low 5-min Apgar score in term newborns due to asphyxia?
AB  - OBJECTIVE: To evaluate how often low 5-min Apgar scores (AS(5-min)) at term are
      associated with asphyxia. STUDY DESIGN: A cohort- and case-control study,
      including all 183 term infants with AS(5-min) below 7 born at Lund University
      Hospital during 1993-2002, antepartum deaths excluded. The control group included
      183 randomly selected term newborns with AS(5-min) 9-10. Cardiotocography (CTG)
      traces were assessed blinded to group and outcome. Obstetric and pediatric files
      were reviewed. RESULTS: After excluding infants with severe malformations,
      indications of hypoxia were found at the following rates in cases with AS(5-min)
      below 4 (N = 30), scores 4-6 (N = 143), and controls (N = 182)-abnormal admission
      CTG: 38%, 8% and 0.6%; abnormal CTG before birth: 88%, 69% and 18%; obstetrical
      catastrophe: 28%, 6% and 0.6%; interventions for fetal distress: 83%, 48% and 9%;
      cord artery pH below 7.15: 69%, 54% and 7%; hypoxic ischemic encephalopathy or
      hypoxic death: 70%, 14% and none. All differences between each case group and
      controls were statistically significant (p < 0.0001). CONCLUSIONS: In the absence
      of severe malformations, the vast majority of AS(5-min) below 4, and at least
      half of scores 4-6 could be attributed to birth asphyxia. Signs of hypoxia
      usually appeared during labor, but were present at admission in 38% of cases with
      AS(5-min) below 4.

PMID- 16621223
TI  - Rupture of tubal pregnancy in the Vilnius population.
AB  - OBJECTIVES: To evaluate the determinants of tubal rupture in women who suffered
      from ectopic pregnancy in relation to their demographic profile and medical
      history. STUDY DESIGN: This retrospective observational clinical study was
      conducted in five general hospitals in Vilnius, Lithuania. The population was
      composed of 879 women with surgically proven ectopic pregnancy. Tubal rupture was
      diagnosed at the time of surgery. Univariate and multivariate logistic regression
      analyses were performed to identify the risk factors for tubal rupture. RESULTS:
      The occurrence of tubal rupture was 29.5% (259/879). It was encountered
      significantly more often in women with age of > or =35 years (odds ratio 1.9 [1.3
      2.8]). Patients whose EP was located in the isthmus were at higher risk of having
      tubal rupture (odds ratio 3.2 [2.2-4.5]) while known risk factors for EP were not
      associated with an elevated risk. CONCLUSIONS: Our data suggest that age of > or
      =35 years and implantation in the straightest segment of the tube could be
      associated with increased rate of tubal rupture. Of particular interest is the
      overall tubal rupture prevalence (29.5%) observed since these women were managed
      in an environment where transvaginal ultrasound equipment and quantitative
      assessment of beta-human chorionic gonadotrophin were not routinely available.

PMID- 16621224
TI  - TVT and TVT-Obturator: comparison of two operative procedures.
AB  - AIM: To compare two anti-incontinence operations: the tension-free vaginal tape
      (TVT) and the TVT-Obturator for the first two 75-patient groups. METHODS: One
      surgeon operated on two patient groups with urodynamically proven urinary stress
      incontinence. The first 75-patient group in 1998 included the first TVT
      procedures performed according to Ulmsten [Ulmsten U, Henriksson L, Johnson P,
      Varhos G. An ambulatory surgical procedure under local anesthesia for treatment
      of female urinary incontinence. Int Urogynecol J 1996;7:81-6]. Follow-up lasted
      for 5-6 years. The second 75-patient group in 2004 included the first TVT
      Obturator operations performed according to [De Leval J. Novel surgical technique
      for the treatment of female stress urinary incontinence: transobturator vaginal
      tape inside-out. Eur. Urol. 2003;44:724-30]. Follow-up lasted for 6-13 months.
      RESULTS: The two patient groups were similar from the demographic and therapeutic
      points of view. The TVT-Obturator procedure required neither bladder
      catheterization nor intra-operative diagnostic cystoscopy. TVT-related bladder
      penetration (8.0%), post-operative voiding difficulties (5.0%), intra-operative
      bleeding (4.0%), post-operative field infection (2.7%), and post-operative pelvic
      floor relaxation (1.3%) were not noted with the TVT-Obturator. The early
      therapeutic failure rates were 2.7% for the TVT and 1.3% for the TVT-Obturator,
      and neither bowel nor urethral injuries were recorded. CONCLUSIONS: The surgeons'
      learning curves of these two minimally invasive surgical procedures for the
      treatment of female urinary stress incontinence are comparable. The safety and
      cost-effectiveness of the TVT are well-established. The TVT-Obturator, a novel
      mid-urethral sling, was designed to overcome some of the TVT-related operative
      complications. The TVT-Obturator patients seem to have less intra-operative and
      post-operative surgical complications than the TVT patients. However, long-term
      comparative data collection is required prior to drawing solid conclusions
      concerning the superiority of one of these two operative techniques.

PMID- 16621225
TI  - Post-neonatal health and development of children born after assisted
      reproduction: a systematic review of controlled studies.
AB  - Long-term follow-up studies on the health and the development of children
      conceived by assisted reproduction (ART) are mandatory to assess the safety of
      ART. Meanwhile, different aspects of health of these children have been studied.
      To put these results together, we performed a systematic review of these
      publications. A Pubmed search and a hand-search of the abstract books from the
      annual meeting of the European Society of Human Reproduction and Embryology and
      the American Society of Reproductive Medicine were performed for controlled
      studies on the developmental outcome of children after ART, which include a
      matching for plurality of gestation. Regarding general health, growth, mental and
      psychomotor development IVF children do not differ from spontaneously conceived
      (SC) children. An increased need for surgical interventions may be due to an
      increase in the malformation rate. However, a lower birth weight and lower
      gestational age compared to matched controls may contribute to some health
      problems observed. The increased risk of neurological problems found in some
      large registry-based studies can partly be explained by the higher frequency of
      twins born, by low birth weight, and by low gestational age also found in
      singletons. But an effect of IVF, the parents' infertility or other factors not
      adjusted for in the studies cannot be excluded. In addition to this reporting
      bias caused by concerned parents cannot be excluded, either. To conclude,
      children born after assisted reproductive techniques are generally healthy and
      are developmentally similar to children born after SC. However, low birth weight
      and prematurity contributes to health care problems. An increase of neurological
      problems by IVF cannot be excluded. Further prospective studies on the
      neurological outcome are needed.

PMID- 16621226
TI  - Severe hypertension in pregnancy: hydralazine or labetalol. A randomized clinical
      trial.
AB  - OBJECTIVE: The objective was to compare the safety and efficacy of intravenous
      labetalol and intravenous hydralazine for acutely lowering blood pressure in
      pregnancy. STUDY DESIGN: Two hundred women with severe hypertension in pregnancy
      were randomized to receive hydralazine (5 mg as a slow bolus dose given
      intravenously, and repeated every 20 min up to a maximum of five doses) or
      labetalol (20-mg intravenous bolus dose followed by 40 mg if not effective within
      20 min, followed by 80 mg every 20 min up to a maximum dose of 300 mg). The
      primary end point was successful lowering of blood pressure and maternal
      hypotension. RESULTS: Women were similar with respect to characteristics at
      randomization. No significant differences were observed for maternal hypotension
      or persistent severe hypertension; only two patients in the hydralazine group
      presented with hypotension. Palpitations (p=0.01) and maternal tachycardia
      (p=0.05) occurred significantly more often in patients treated with hydralazine.
      The main neonatal outcomes were very similar per group; however, hypotension and
      bradycardia were significantly more frequent in the labetalol group. There were
      two neonatal deaths per antihypertensive drug group. CONCLUSIONS: This randomized
      clinical trial shows that labetalol and hydralazine fulfill the criteria required
      for an antihypertensive drug to treat severe hypertension in pregnancy.

PMID- 16621227
TI  - Is inferior dissection of the rectus sheath necessary during Pfannenstiel
      incision for lower segment Caesarean section? A randomised controlled trial.
AB  - OBJECTIVE: The objective was to determine the benefit of non-dissection of the
      rectus sheath inferiorly in a Pfannenstiel incision during an elective Caesarean
      section with regard to operative blood loss and post-operative pain. DESIGN: A
      randomised controlled trial. SETTING: The Royal Free Teaching Hospital in London.
      POPULATION: One hundred and twenty women who underwent elective Caesarean section
      delivery. METHOD: Women were randomised to have dissection or non-dissection of
      the rectus sheath inferiorly during an elective Caesarean section. MAIN OUTCOME
      MEASURES: Estimated blood loss during the operation, as well as the difference
      between pre- and post-operative haemoglobin levels. Post-operative pain was
      assessed by the visual analogue scale, a verbal rating scale and the use of post
      operative analgesia. Patient satisfaction was assessed by a verbal rating scale.
      RESULTS: There was no significant difference in the estimated blood loss during
      the procedure between the two groups; however, the mean difference between the
      pre-operative and post-operative haemoglobin was significantly smaller in the
      study group (p=0.05). There was a statistically significant difference in both
      the visual analogue scale (p-value=0.03) and the verbal rating scale scores (p
      value=0.02) for pain between the two groups, with lower scores for the study
      group. There was no overall difference in the verbal rating scale scores for
      patient satisfaction. CONCLUSION: Non-dissection of the rectus sheath inferiorly
      in Pfannenstiel incisions during Caesarean section procedures is associated with
      a significant reduction in the post-operative pain as well as a smaller drop in
      post-operative haemoglobin.

PMID- 16621228
TI  - Atrial hemangioma: a rare cause of hydrops fetalis and intrauterine fetal death.

PMID- 16621229
TI  - Extended breast cancer treatment with an aromatase inhibitor (Letrozole) after
      tamoxifen: why, who and how long?
AB  - Breast cancer remains a leading cause of cancer death in women worldwide, and the
      risk for disease recurrence continues despite improvements in screening and
      treatment and the use of prophylactic estrogen-inhibiting therapies such as
      tamoxifen. A number of long-term studies now indicate a significant risk for
      breast cancer recurrence among patients who have undergone the currently
      recommended five years of tamoxifen adjuvant therapy following successful
      treatment of their initial disease. This ongoing recurrence risk extends even to
      patients commonly considered at low risk for relapse, that is, those with low
      grade, small tumors, and/or node-negative disease. Treatment with tamoxifen for
      more than five years appears detrimental rather than beneficial and, therefore,
      tamoxifen is not indicated for use beyond the initial five years. Endometrial
      cancer and thromboembolism are among the serious adverse events that have been
      observed with long-term tamoxifen treatment. The aromatase inhibitors are able to
      reduce overall estrogen levels and appear to be better tolerated over a long
      term. Letrozole is the most potent aromatase inhibitor and has been available in
      Europe since 1996 and in the United States since 1997. Letrozole has been
      approved for first-line treatment of postmenopausal women with hormone-receptor
      positive or hormone-receptor-unknown, advanced or metastatic breast cancer in the
      United States and Europe, as well as for neoadjuvant treatment (primary systemic
      therapy) of early breast cancer prior to surgery in many countries. The results
      of the pivotal MA-17 trial demonstrate that letrozole is unique in its ability to
      improve disease-free survival in breast cancer patients who have undergone
      tamoxifen therapy for five years. The MA-17 results indicate that extended
      adjuvant therapy with letrozole reduces risk of recurrence in this setting by
      42%, reduces risk of distant recurrence (metastasis), and may improve patient
      survival in the node-positive patient population. The results also show letrozole
      to be well tolerated and safe over the length of follow-up. The trial outcomes
      have led to the approval of letrozole for the extended adjuvant indication in
      more than 40 countries worldwide. Re-randomization of letrozole-treated patients
      from this pivotal trial is underway to investigate if ten years of extended
      adjuvant endocrine therapy leads to further improvement, and the results of this
      extension study should aid in resolving several open questions regarding extended
      adjuvant therapy, including who should be treated and for how long.

PMID- 16621230
TI  - Group B Streptococcus carriers among HIV-1 infected pregnant women: prevalence
      and risk factors.
AB  - OBJECTIVE: The objective was to determine the frequency and risk factors of
      anogenital colonization by Streptococcus agalactiae (GBS) in pregnant women
      infected with human immunodeficiency virus type 1 (HIV-1). STUDY DESIGN: A
      prospective study was conducted on 207 pregnant women divided into two groups:
      HIV group (n=101) and a control group consisting of HIV-uninfected pregnant women
      (n=106) to assess regional colonization by GBS. Anal and vaginal swabs were
      collected and cultured in Todd-Hewitt broth, followed by a confirmatory test. For
      a control group with an anticipated proportion based on literature research of 10
      30% and alpha=0.05, a sample size of 100 would have a power of 80% to detect a
      difference of 15% or greater with a study group. The mothers were studied in
      terms of frequency of anogenital colonization by GBS, maternal epidemiological
      data, and TCD4 lymphocyte counts. The results were analyzed using the chi(2)
      test, Fisher's exact test and the Student's t-test, with the level of
      significance set at p<0.05. RESULTS: Twenty (19.8%) HIV-1-infected pregnant women
      were found to be colonized by GBS at between 35 and 37 weeks' gestation. In the
      control group, the prevalence of GBS was 14.1%. CONCLUSION: No significant
      increase in GBS colonization was observed in HIV-1-infected pregnant women.
      Maternal colonization of GBS in HIV-infected pregnant women was not found to be
      associated with their immunological status. Sexual contact does not seem to be
      the principal way of transmitting GBS.

PMID- 16621231
TI  - Factors influencing the acceptance of nature conservation measures--a qualitative
      study in Switzerland.
AB  - Landscapes fulfil a multitude of ecological and social functions. Due to the fact
      that both traditional and everyday landscapes today face many different threats,
      regulatory measures have been undertaken in many countries to protect and further
      sustainable landscape development. They include legislation as well as economic
      incentives. In recent years, however, it has become clear that just to have a few
      laws and to spend money on subsidies is not enough. Factors other than
      legislation are also essential to further the sustainable development of
      landscapes. One of the basic factors affecting the success or failure of
      landscape conservation measures is public acceptance of these measures. Our
      project took this as its starting point. The objective was to determine which
      conditions and factors influence acceptance positively or negatively. To this end
      22 Swiss who are directly affected by nature conservation measures, in particular
      by mire landscape and dry meadow conservation measures, were interviewed using
      qualitative interview techniques. It is shown that perception, communication, and
      possibilities to participate are the most decisive driving factors influencing
      the formation of a long-lasting acceptance. Furthermore, acceptance may be based
      mainly on economic criteria, on usefulness, on ecological or even aesthetic
      aspects. It can be shown that not all of these motivations lead to a long-lasting
      acceptance. Ecologically based acceptance seems the most promising because it is
      founded on general convictions. Economic incentives--though important--seem to
      generate only superficial acceptance and do not seem to be as important as is
      usually assumed.

PMID- 16621232
TI  - Geostatistical spatiotemporal analysis of air temperature as an aid to
      delineating thermal stability zones in a potential show cave: implications for
      environmental management.
AB  - Air temperature in several galleries of the Covadura System (Sorbas Gypsum Karst,
      Almeria) was measured at monthly intervals over a period of 1 year. The spatial
      temperature distribution for each month was modeled in a geostatistical
      framework. The mean trend of the air temperature and the difference between each
      experimental temperature measurement and this trend were calculated over space
      and time. Both the trend and residual component were characterized using a
      geostatistical space-time model. A large spatial trend of the air temperature was
      found due to the orientation of galleries within the cave system and as a
      function of the distance from the main cave entrance. Kriging was used for the
      spatial estimation of the time covariance of the residuals. This enabled the
      delimitation of the cave into three zones of varying environmental risk in the
      event of being opened to visits by the public, according to the degree of
      stability of air temperature over space and time. The influence of human presence
      on the spatial temperature distribution was assessed using data collected during
      a year (2000/2001) in pilot galleries opened to the public. An average visit
      corresponding to August was selected comprising 16 people over a period of 53
      min. This average visit influenced the spatial temperature pattern at distances
      of more than 90 m from the cave entrance, according to the geostatistical model
      adopted. Within this zone the mean thermal increment generated by human presence
      was estimated to be 0.26 degrees C. The spatiotemporal mathematical model of the
      cave air temperature has been revealed as a useful tool for the environmental
      management of show caves.

PMID- 16621233
TI  - Environmental planning vs. systems analysis: four prescriptive principles vs.
      four descriptive indicators.
AB  - Four principles for a systems approach to sustainability, which have been
      suggested as prescriptive, normative and desirable, are analysed. Limitations in
      the principles are observed. The four principles are developed into descriptive
      indicators, metrics or tools that can be used in sustainability systems analysis
      to study important properties of all complex systems.

PMID- 16621234
TI  - Protein kinase C modulates ecdysteroidogenesis in the prothoracic gland of the
      tobacco hornworm, Manduca sexta.
AB  - The prothoracic gland is the primary source of ecdysteroid hormones in the
      immature insect. Ecdysteroids coordinate gene expression necessary for growth,
      molting and metamorphosis. Prothoracicotropic hormone (PTTH), a brain
      neuropeptide, regulates ecdysteroid synthesis in the prothoracic gland. PTTH
      stimulates ecdysteroid synthesis through a signal transduction cascade that
      involves at least four protein kinases: protein kinase A (PKA), p70 S6 kinase, an
      unidentified tyrosine kinase, and the extracellular signal-regulated kinase
      (ERK). In this report, the participation of protein kinase C (PKC) in PTTH
      signalling is demonstrated and characterized. PTTH stimulates PKC activity
      through a PLC and Ca(2+)-dependent pathway that is not cAMP regulated. Inhibition
      of PKC inhibits PTTH-stimulated ecdysteroidogenesis as well as PTTH-stimulated
      phosphorylation of ERK and its upstream regulator, MAP/ERK kinase (MEK). These
      observations reveal that the acute regulation of prothoracic gland
      steroidogenesis is dependent on a web of interacting kinase pathways, which
      probably converge on factors that regulate translation.

PMID- 16621235
TI  - Lactoferrin (Lf): Retinoid interactions in the mammary glands of transgenic mice
      overexpressing human Lf.
AB  - Induction of protein expression in a tissue-specific manner by gene transfer over
      expression techniques has been one means to define the function of a protein in a
      biological paradigm. Studies with retinoid reporter constructs transfected in
      mammary cell lines suggests that lactoferrin (Lf) affects retinoid signaling
      pathways and alters apoptosis. We tested the effects and interactions of over
      expressed mammary-specific human lactoferrin (hLf) and dietary retinol palmitate
      on lactation and mammary gland development in mice. Increased retinol palmitate
      in the diet increased daily retinol equivalents (RE) to 2.6-fold over the normal
      mouse control diet. Transgene (Tg) expression in the dam fed control diet
      depressed pup weight gain. Severe depression of pup weight gain was observed when
      homozygote TgTg dams were fed the RE diet. Normal weight gain was restored when
      pups were placed with a wild type dam fed the RE diet; conversely, normal growing
      pups from the wild type dams showed declining weight gains when fostered to the
      TgTg RE-fed dams. Northern analysis of mammary tissue extracts showed a reduction
      in WAP and an increase in IGFBP-3 mRNA that was associated with the presence of
      the transgene. Histological evaluation of 3 days lactating mammary tissue showed
      mammary epithelial cells from TgTg animals contained excessive secretory
      products, suggesting a block in cellular secretion mechanisms. In addition, the
      mammary cells displayed a cellular apical membrane puckering that extended into
      the alveoli lumens. These studies demonstrate an in vivo interaction of Tg-hLf
      expression and dietary retinoids in mouse mammary glands. While normal mammary
      gland physiology may not be representative by these experiments because high Lf
      concentrations during early lactation are abnormal, the demonstrated biological
      interaction suggests that typical periods of high Lf concentrations may have
      impact upon developing and involuting mammary glands.

PMID- 16621236
TI  - Identification of zinc finger binding protein 89 (ZBP-89) as a transcriptional
      activator for a major bovine growth hormone receptor promoter.
AB  - The objective of this study was to identify the transcription factors that
      regulate the expression of growth hormone receptor (GHR) 1A mRNA, a major GHR
      mRNA variant in the bovine liver. A deoxyribonuclease I footprint analysis
      revealed that the GHR1A promoter region -69 to -30 (relative to the transcription
      start site for GHR1A mRNA) contained binding sites for bovine liver nuclear
      proteins. Using a yeast one-hybrid analysis, zinc finger binding protein 89 (ZBP
      89) was identified as a binding protein to this promoter region. Binding of ZBP
      89 to the GHR1A promoter region -69 to -30 was further confirmed by an
      electrophoretic mobility shift assay. In cotransfection analyses, overexpression
      of ZBP-89 enhanced (P<0.01) the activity of the GHR1A promoter and this
      enhancement was dependent on the putative ZBP-89 binding site in the promoter.
      These results together indicate that ZBP-89 is a transcription factor that
      regulates the expression of GHR1A mRNA.

PMID- 16621238
TI  - Pilocytic astrocytoma with spontaneous intracranial hemorrhages in an elderly
      adult.
AB  - Pilocytic astrocytomas are relatively uncommon tumors found predominantly in the
      pediatric population. Reports of these tumors are extremely rare in the elderly.
      This is a report of a 75-year-old man presenting with two spontaneous
      intracranial hemorrhages and subsequent resection of a pilocytic astrocytoma. The
      history, evaluation, radiographic features, histopathology, rationale for surgery
      and potential mechanism of hemorrhage are discussed. A review of the literature
      summarizes the current field of knowledge of adult pilocytic astrocytomas in the
      setting of intracranial hemorrhage.

PMID- 16621237
TI  - Other causes of ataxia in patients with SCA mutations.
AB  - Autosomal dominant spinocerebellar ataxias (SCAs) are slowly progressive and have
      a variable clinical presentation. Overlapping clinical features among the SCAs
      make the clinical diagnosis of these ataxias difficult. Even when genetic testing
      identifies an SCA mutation, clinicians should be vigilant for other causes of
      neurological dysfunction in these patients. We report two patients who developed
      other causes of ataxia in the setting of SCA-3 and SCA-8 mutations, respectively.

PMID- 16621239
TI  - Paroxysmal neuralgic upper cervical pain attacks: the lower syndrome of cluster
      headache.
AB  - We present a group of seven patients with a lower syndrome (LS) of cluster
      headache (CH). Seventy-three newly diagnosed patients with CH were subjected to a
      9 years follow-up study; 66 patients were classified as upper syndrome (US) and
      only seven patients (9.5%) as LS. We focus on the characteristics of this group
      of seven patients with LS and compare them with existing literature. The seven
      cases with LS illustrate the wider spectrum of clinical manifestations that can
      occur in CH, namely infraortibal symptoms or these outside the territory of the
      trigeminal branches such as the upper cervical region or the craniocervical
      margin. The duration of the attacks can last more than 180 min. The attacks show
      a circadian/circannual regularity and a stereotypic pattern of symptoms in most
      of the patients. The severity and duration of the attacks may increase over the
      years. The neck pain can overshadow all the other symptoms of CH. Because of the
      regularity of the attacks at particular times of day or night in some patients,
      even abortive therapy can be used as prevention when taken some hours before the
      suspected attack. We hypothesize that some patients with LS may represent an
      anatomical-functional variant of a primary chronic neurovascular pain disorder
      originating from the central nervous system, with possible involvement of the
      hypothalamus and the trigeminovascular (TV) system, with inputs from the cervical
      roots C(0)-C(2). Clinicians should consider CH when pain attacks are located
      outside the orbitotemporal regions, but fulfil the other diagnostic criteria for
      CH and should try ergotamine, oxygen, sumatriptan, verapamil, steroids or even
      combinations in these patients.

PMID- 16621240
TI  - Segmental left ventricular wall motion abnormalities are associated with lacunar
      ischemic stroke.
AB  - OBJECTIVE: The aim of this study was to determine whether segmental left
      ventricular wall motion abnormalities (SLVWMA) are a potential cause of ischemic
      stroke. METHODS: Demographics, cardiovascular risk factors and echocardiographic
      parameters of patients with ischemic stroke (with and without SLVWMA) were
      collected and compared with those of patients who had SLVWMA but without history
      of ischemic stroke. RESULTS: Two hundred and fifty nine patients with ischemic
      stroke were identified: 187 patients without SLVWMA, and 72 with SLVWMA. The
      cardiac group consisted of 79 patients. Compared with the stroke patients with
      SLVWMA, stroke patients without SLVWMA were slightly but significantly younger
      (59 versus 63 years of age). Furthermore, the number of risk factors in stroke
      patients without SLVWMA was significantly lower compared with stroke patients
      with SLVWMA (2.7 versus 3.7). There was no difference in age or gender between
      stroke patients with SLVWMA and the cardiac patients. However, the number of risk
      factors was significantly higher in the cardiac patients compared with stroke
      patients with SLVWMA (4.4 versus 3.7). The ejection fraction was normal in both
      groups of stroke patients but significantly lower in the cardiac patients (37%).
      Significantly more lacunar ischemic strokes were observed in stroke patients with
      SLVWMA than in those without SLVWMA (76% versus 68%). CONCLUSION: Our data
      indicate that in ischemic stroke patients with multiple cardiovascular risk
      factors and SLVWMA a higher frequency of lacunar strokes can be found. The latter
      could be a marker of small-vessel disease and/or be a potential contributing
      factor, perhaps through a mechanism of cardiac microembolism, in the development
      of lacunar ischemic stroke. The mechanisms of the association between SLVWMA and
      lacunar ischemic stroke remain however unclear.

PMID- 16621241
TI  - Anti-GAD antibody cerebellar ataxia mimicking Creutzfeldt-Jakob disease.
AB  - In a patient with a rapidly progressive neurological condition with ataxia and
      cognitive complaints, Creutzfeldt-Jakob disease (CJD) is often high in the
      differential, particularly when there is an elevated CSF 14-3-3 protein level. We
      present a case of anti-glutamic acid decarboxylase antibody (anti-GAD65) positive
      cerebellar ataxia associated with cognitive complaints and elevated CSF 14-3-3
      protein.

PMID- 16621242
TI  - Is the increase in osteoporosis prevention a result of the audit?

PMID- 16621243
TI  - Structural, functional and therapeutic biology of survivin.
AB  - Survivin is a unique member of the inhibitor of apoptosis (IAP) protein family
      that interferes with post-mitochondrial events including activation of caspases.
      Survivin regulates cell cycle also. It is expressed in most of the human tumors,
      but it is barely detectable in the terminally differentiated normal
      cells/tissues. Molecular mechanisms of regulation of survivin in cancer are not
      clearly understood. Nevertheless, the functional loss of wild type p53 is often
      associated with upregulation of survivin. Tumors that over-express survivin
      generally bear a poor prognosis and are associated with resistance to therapy.
      The differential expression of survivin in cancer versus normal tissues makes it
      a useful tool in cancer diagnosis and a promising therapeutic target. A growing
      body of literature suggests nuclear expression of survivin as a good prognostic
      marker. Disruption of the survivin induction pathway has resulted in an increase
      in apoptosis and inhibition of tumor growth. Regular therapies, such as,
      radiotherapy in combination with anticancer drugs in clinical practice may yield
      promising results.

PMID- 16621244
TI  - Schisandrin B: a dual inhibitor of P-glycoprotein and multidrug resistance
      associated protein 1.
AB  - We recently reported that schisandrin B (Sch B) was a novel P-glycoprotein (P-gp)
      inhibitor. In this study, we revealed that Sch B was also an effective inhibitor
      of multidrug resistance-associated protein 1 (MRP1). The activities of Sch B to
      reverse MRP1-mediated drug resistance was tested using HL60/ADR and HL60/MRP, the
      human promyelocytic leukemia cell lines with the overexpression of MRP1 but not P
      gp. Sch B resumed daunorubicin and carboxyfluorescein diacetate (CFDA, a specific
      substrate for MRP1) accumulation and retention in HL60/ADR cells in a time and
      concentration dependent manner. At the equimolar concentration, Sch B
      demonstrated significantly stronger potency than probenecid, a MRP1 inhibitor.
      This study, together with the previous findings, demonstrated that Sch B was a
      dual inhibitor of P-gp and MRP1, a type suggested to be preferable to the use of
      combination of two specific modulators to prevent drug-drug interaction and
      cumulative toxicities.

PMID- 16621245
TI  - Differential effects of bisphosphonates on breast cancer cell lines.
AB  - Bisphosphonates may induce direct anti-tumor effects in breast cancer cells in
      vitro. In this study, six bisphosphonates were administered to three breast
      cancer cell lines. Cell proliferation was measured by quantification of the
      expression of Cyclin D1 mRNA. Apoptosis was determined by flow cytometry of a DNA
      fragmentation assay. We demonstrated that bisphosphonates have direct effects on
      cell proliferation and apoptosis in different breast cancer cell lines. However,
      not all bisphosphonates act equally on breast cancer cells in vitro. Zoledronate
      seems to be the most potent of the six bisphosphonates. This in vitro study
      showed that bisphosphonates possess promising anti-tumor potential.

PMID- 16621246
TI  - Assessment of the mineral industry NORM/TENORM disposal in hazardous landfills.
AB  - The main objective of this paper is to describe the assessment methodology
      utilised in Brazil, to foresee the performance of industrial landfills to
      disposal solid wastes containing natural radionuclides arising from milling and
      metallurgical installations that process ores containing NORM. An integrated
      methodology is utilized and issues as risk, exposure pathways and the plausible
      scenarios in which the contaminant can migrate and reach the environment and
      human beings are addressed. A specific example of the procedure is described and
      results are presented for actual situations. The model consists of an engineered
      depository constructed of earthen materials which minimise costs and maintain
      integrity over long-term. In order to define the landfill characteristics and the
      potential consequences to the environment, an impact analysis is carried out,
      considering the engineering aspects of the waste deposit and the exposure
      pathways by which the contaminant can migrate and reach the environment and human
      beings. Analytical solutions are used in the computer program in order to obtain
      fast results.

PMID- 16621247
TI  - The adsorption of Cd(II) ions on sulphuric acid-treated wheat bran.
AB  - The adsorption of Cd(II) ions which is one of the most important toxic metals by
      using sulphuric acid-treated wheat bran (STWB) was investigated. The effects of
      solution pH and temperature, contact time and initial Cd(II) concentration on the
      adsorption yield were studied. The equilibrium time for the adsorption process
      was determined as 4 h. The adsorbent used in this study gave the highest
      adsorption capacity at around pH 5.4. At this pH, adsorption capacity for an
      initial Cd(II) ions concentration of 100 mg/L was found to be 43.1 mg/g at 25
      degrees C for contact time of 4 h. The equilibrium data were analysed using
      Langmuir and Freundlich isotherm models to calculate isotherm constants. The
      maximum adsorption capacity (qmax) which is a Langmuir constant decreased from
      101.0 to 62.5 mg/g with increasing temperature from 25 to 70 degrees C. Langmuir
      isotherm data were evaluated to determine the thermodynamic parameters for the
      adsorption process. The enthalpy change (deltaH(o)) for the process was found to
      be exothermic. The free energy change (deltaG(o)) showed that the process was
      feasible. The kinetic results indicated that the adsorption process of Cd(II)
      ions by STWB followed first-order rate expression and adsorption rate constant
      was calculated as 0.0081 l/min at 25 degrees C. It was observed that the
      desorption yield of Cd(II) was highly pH dependent.

PMID- 16621248
TI  - Cu2+, Cd2+ and Pb2+ adsorption from aqueous solutions by pyrite and synthetic
      iron sulphide.
AB  - In this study, removal of Cu(2+), Cd(2+) and Pb(2+) from aqueous solutions by
      adsorption onto pyrite and synthetic iron sulphide (SIS) was investigated as a
      function of pH, contact time, adsorbent dosage, initial metal concentration and
      temperature. It has been determined that the adsorption of metal ions onto both
      adsorbents is pH dependent and the adsorption capacities increase with the
      increasing temperature. The mechanisms governing the metal removal processes were
      determined as chemical precipitation at low pH (<3) due to H(2)S generation and
      adsorption at high pH (in the range of 3-6). The metal adsorption yields also
      increased with the increasing adsorbent dosage and contact time and reached to
      equilibrium for both adsorbents. The Cu(2+), Cd(2+) and Pb(2+) adsorption
      capacities of both adsorbents decrease in the order of Pb(2+)>Cu(2+)>Cd(2+).
      Except for cadmium, little fraction of copper and lead in the solid adsorption
      residues was desorbed in acidic media.

PMID- 16621249
TI  - Utilisation of MSWI bottom ash as sub-base in road construction: first results
      from a large-scale test site.
AB  - The preferred management option for municipal solid waste incinerator (MSWI)
      bottom ash in Denmark is utilisation rather than landfilling, but the current
      environmental quality criteria for bottom ash to be utilised in bulk quantities
      are rather strict. To evaluate the impact and risk assessments, upon which those
      criteria are based, a large-scale test site has been established. Three different
      MSWI bottom ashes have been used as sub-base in six test units ranging from 100
      to 200 m2 with top covers of asphalt, flagstones and pebbles, respectively. All
      units, except one, are equipped with bottom liners and leachate collection
      equipment. The test site provides information on the leachate quality and
      quantity as a function of time under different conditions and on the flow pattern
      in asphalt and flagstone covered roads and squares with MSWI bottom ash sub-base.
      In addition, the leaching behaviour of the bottom ashes has been studied in the
      laboratory. The test site was established in October 2002 and the project is
      still ongoing. Water balance results indicate that the water flow distribution is
      strongly influenced by lateral flow on or in the upper part of the bottom ash
      layer and possibly by preferential flow. Comparisons between eluates from
      laboratory leaching tests on the bottom ashes and observations of the leachate
      from the site as a function of L/S show fairly good agreement for salts but less
      agreement for some trace elements. Most likely, this is partly due to the fact
      that the pH observed in the leachate from the field sites is lower than that
      observed in the eluates from the laboratory leaching tests.

PMID- 16621250
TI  - Use of Ponkan mandarin peels as biosorbent for toxic metals uptake from aqueous
      solutions.
AB  - Waste Ponkan mandarin (Citrus reticulata) peel was used as biosorbent to extract
      Ni(II), Co(II) and Cu(II) from aqueous solutions at room temperature. To achieve
      the best adsorption conditions the influence of pH and contact time were
      investigated. The isotherms of adsorption were fitted to the Langmuir equation.
      Based on the capacity of adsorption of the natural biosorbent to interact with
      the metallic ions, the following results were obtained 1.92, 1.37 and 1.31 mmol
      g(-1) for Ni(II), Co(II) and Cu(II), respectively, reflecting a maximum
      adsorption order of Ni(II)>Co(II)>Cu(II). The quick adsorption process reached
      the equilibrium before 5, 10 and 15 min for Ni(II), Co(II) and Cu(II),
      respectively, with maximum adsorptions at pH 4.8. In order to evaluate the Ponkan
      mandarin peel a biosorbent in dynamic system, a glass column was fulfilled with
      1.00 g of this natural adsorbent, and it was fed with 5.00 x 10(-4)mol l(-1) of
      Ni(II) or Co(II) or Cu(II) at pH 4.8 and 3.5 ml min(-1). The lower breakpoints
      (BP(1)) were attained at concentrations of effluent of the column attained the
      maximum limit allowed of these elements in waters (>0.1 mg l(-1)) which were:
      110, 100 and 130 bed volumes (V(effluent)/V(adsorbent)), for Ni(II), Co(II) and
      Cu(II), respectively. The higher breakpoints (BP(2)) were attained when the
      complete saturation of the natural adsorbent occurred, and the values obtained
      were: 740, 540 and 520 bed volumes for Ni(II), Co(II) and Cu(II), respectively.

PMID- 16621251
TI  - The dynamic adsorption characteristics of phenol by granular activated carbon.
AB  - The objective of the present work is to determine the operating conditions of an
      activated carbon filter, based on the characteristics of breakthrough curves. For
      this we apply the technical developed by Mickaels for the ionic exchange and
      applied by Luchkis for the adsorption, and which is the mass transfer zone. To
      reach our goal, an evaluation of the operating conditions (height of the bed,
      flow and concentration of effluent) on the characteristics of the mass transfer
      zone was made and an explanation of the mechanism of adsorption was given.
      Thereafter a modeling of the experimental results was done.

PMID- 16621252
TI  - Biosorption of 2,4-dichlorophenol from aqueous solution by Phanerochaete
      chrysosporium biomass: isotherms, kinetics and thermodynamics.
AB  - The biosorption of 2,4-dichlorophenol (2,4-DCP) from aqueous solution on non
      living mycelial pellets of Phanerochaete chrysosporium was studied with respect
      to pH, initial concentration of 2,4-DCP, temperature and pellet size. The fungal
      biomass exhibited the highest sorption capacity of 4.09 mg/g at an initial pH of
      5.0, initial 2,4-DCP concentration of 50.48 mg/l, 25 degrees C and a pellet size
      of 1.0-1.5 mm in the investigated pH 2.0-11.0, initial concentrations of 5-50
      mg/l, temperature 25-50 degrees C, and pellet size of 1.0-2.5 mm. The Freundlich
      model exhibited a slightly better fit to the biosorption data of 2,4-DCP than the
      Langmuir model. The biosorption of 2,4-DCP to biomass followed pseudo second
      order adsorption kinetics. The second-order kinetic constants decreased with
      increasing temperature, and the apparent activation energy of biosorption was
      estimated to be -16.95 kJ/mol. The thermodynamic analysis indicates that the
      biosorption process was exothermic and that the adsorption of 2,4-DCP on P.
      chrysosporium might be physical in nature. Both intraparticle diffusion and
      kinetic resistances might affect the adsorption rate and that their relative
      effects varied with operation temperature in the biosorption of 2,4-DCP by
      mycelial pellets.

PMID- 16621253
TI  - Hot water extraction with in situ wet oxidation: kinetics of PAHs removal from
      soil.
AB  - Finding environmentally friendly and cost-effective methods to remediate soils
      contaminated with polycyclic aromatic hydrocarbons (PAHs) is currently a major
      concern of researchers. In this study, a series of small-scale semi-continuous
      extractions--with and without in situ wet oxidation--were performed on soils
      polluted with PAHs, using subcritical water (i.e. liquid water at high
      temperatures and pressures, but below the critical point) as the removal agent.
      Experiments were performed in a 300 mL reactor using an aged soil sample. To find
      the desorption isotherms and oxidation reaction rates, semi-continuous
      experiments with residence times of 1 and 2 h were performed using aged soil at
      250 degrees C and hydrogen peroxide as oxidizing agent. In all combined
      extraction and oxidation flow experiments, PAHs in the remaining soil after the
      experiments were almost undetectable. In combined extraction and oxidation no
      PAHs could be detected in the liquid phase after the first 30 min of the
      experiments. Based on these results, extraction with hot water, if combined with
      oxidation, should reduce the cost of remediation and can be used as a feasible
      alternative technique for remediating contaminated soils and sediments.

PMID- 16621254
TI  - Ni(II) removal from aqueous solutions using cone biomass of Thuja orientalis.
AB  - The biomass of terrestrial-plant materials has high removal capacities for a
      number of heavy metal ions. The Ni(II) biosorption capacity of the cone biomass
      of Thuja orientalis was studied in the batch mode. The biosorption equilibrium
      level was determined as a function of contact time, pH, temperature, agitation
      speed at several initial metal ion and adsorbent concentrations. The removal of
      Ni(II) from aqueous solutions increased with adsorbent concentration, temperature
      and agitation speed of the solution were increased. The biosorption process was
      very fast; 90% of biosorption occurred within 3 min and equilibrium was reached
      at around 7 min. It is found that the biosorption of Ni(II) on the cone biomass
      was correlated well (R2 > 0.99) with the Langmuir equation as compared to
      Freundlich, BET Temkin and D-R isotherm equation under the concentration range
      studied. According to Langmuir isotherm, the monolayer saturation capacity (Q(o))
      is 12.42 mg g(-1). The pseudo-first-order, pseudo-second-order and intraparticle
      diffusion kinetic models were applied to test the experimental data for initial
      Ni(II) and cone biomass concentrations. The pseudo-second-order kinetic model
      provided the best correlation of the used experimental data compared to the
      pseudo-first-order and intraparticle diffusion kinetic models. The activation
      energy of biosorption (E(a)) was determined as 36.85 kJ mol(-1) using the
      Arrhenius equation. This study indicated that the cone biomass of T. orientalis
      can be used as an effective and environmentally friendly adsorbent for the
      treatment of Ni(II) containing aqueous solutions.

PMID- 16621255
TI  - A general model for predicting the flash point of miscible mixtures.
AB  - A mathematical model is presented for predicting the flash point of miscible
      mixtures. This model is reducible and adequate for some specified systems as
      proposed previously. Except for multiple aqueous-organic solutions, the
      predictive capability of the reduced form for other miscible mixtures, including
      binary aqueous-organic solutions and flammables-only analogues, has been verified
      previously. The model was validated using the ternary aqueous-organic solutions,
      water+methanol+ethanol/isopropanol. The results of the study confirm that the
      model predicts the flash points of these solutions by utilizing the flash points
      of the individual components. Further, if the binary interaction parameters for a
      ternary aqueous-organic solution are not accessible, a model based upon the
      binary interaction parameters of the binary solutions may provide a very
      acceptable means of predicting the flash point for such a ternary solution
      through comparison of the predicted and experimental data, as demonstrated in
      this study.

PMID- 16621256
TI  - Investigation of entrainment and thermal properties of a cryogenic dense-gas
      cloud using optical measurement techniques.
AB  - Cryogenic dense-gas clouds have been investigated in a heavy-gas channel under
      controlled source and ambient conditions. Advantage is taken from new, non
      intrusive optical measurement techniques (e.g. image correlation velocimetry,
      ICV, and background oriented Schlieren, BOS) providing detailed pictures of the
      temperature and velocity field in relevant regions of the cloud. The ice
      particles in the cloud, formed by nucleation, represent a natural seeding to be
      used as tracers, which have the advantage of behaving passively. Two layers can
      be identified in a cryogenic gas cloud: a lower cold layer, which is visible due
      to the presence of ice particles, and an invisible upper layer, where the ice
      particles have melted, mostly due to heat addition by air entrainment into the
      upper layer. A two-layer model has been applied to a generic element of the
      cloud, where detailed experimental data regarding velocity and temperature are
      available. Thermal- and dilution behaviour can be interpreted by means of the
      model which is presented in detail. A global entrainment parameter is deduced
      allowing a simple comparison with existing experimental information obtained by
      other traditional experimental techniques. The numerical values of the present
      entrainment parameter agree well with the correlations proposed by other authors.
      Thermal effects, such as heat transfer from the ground, appear to be very
      important. In addition, the visible height of the cloud can be predicted in
      relative good agreement with the experimental observations, by means of a thermal
      balance including the phase transition of the ice particles.

PMID- 16621257
TI  - Catalytic oxidation of anionic surfactants by electrochemical oxidation with CuO
      Co2O3-PO4(3-) modified kaolin.
AB  - A new catalytic oxidation of anionic surfactants by electrochemistry method was
      designed and used to investigate the removal of anionic surfactant from simulated
      wastewater. Synergetic effect on COD removal was studied when integrating the
      electrochemical reactor, using porous graphite as anode and cathode, with the
      effective CuO-Co2O3-PO4(3-) modified kaolin catalyst in a single undivided cell.
      The result showed that this combined process could effectively remove anionic
      surfactant. Its COD removal efficiency was much higher than those individual
      processes and could reach up to 90% in 60 min. The operating parameters such as
      initial pH, cell voltage, and current intensity were also investigated. Possible
      theory for COD removal was also proposed to predict the role of modified kaolin,
      electro-catalysis and oxidation in the combined process. The pollutants in
      wastewater could be decreased by the high reactive OH* that produced on the
      surface of catalyst by the decomposition of electrochemical generated H2O2. The
      result indicates that the catalytic oxidation by electrochemistry method is a
      promising wastewater treatment technique.

PMID- 16621258
TI  - Copper(II) and lead(II) removal from aqueous solution in fixed-bed columns by
      manganese oxide coated zeolite.
AB  - The ability of manganese oxide coated zeolite (MOCZ) to adsorb copper and lead
      ions in single- (non-competitive) and binary- (competitive) component sorption
      systems was studied in fixed-bed column. The experiments were applied to quantify
      particle size, bed length, influent flow rate and influent metal concentration on
      breakthrough time during the removal of copper and lead ions from aqueous
      solutions using MOCZ column. Results of fixed-bed adsorption showed that the
      breakthrough time appeared to increase with increase of the bed length and
      decrease of influent metal concentration, but decreased with increase of the flow
      rate. The Thomas model was applied to adsorption of copper and lead ions at bed
      length, MOCZ particle size, different flow rate and different initial
      concentration to predict the breakthrough curves and to determine the
      characteristic parameters of the column useful for process design. The model was
      found suitable for describing the adsorption process of the dynamic behavior of
      the MOCZ column. The total adsorbed quantities, equilibrium uptakes and total
      removal percents of Cu(II) and Pb(II) related to the effluent volumes were
      determined by evaluating the breakthrough curves obtained at different
      conditions. The results suggested that MOCZ could be used as an adsorbent for an
      efficient removal of copper and lead ions from aqueous solution. The removal of
      metal ion was decreased when other additional heavy metal ion was added, but the
      total saturation capacity of MOCZ for copper and lead ions was not significantly
      decreased. This competitive adsorption also showed that adsorption of lead ions
      was decreased insignificantly when copper ions was added to the influent, whereas
      a dramatic decrease was observed on the adsorption of copper ions by the presence
      of lead ions. The removal of copper and lead ion by MOCZ columns followed the
      descending order: Pb(II) > Cu(II). The adsorbed copper and lead ions were easily
      desorbed from MOCZ with 0.5 mol l(-1) HNO3 solution.

PMID- 16621259
TI  - Oxidation of the pesticide atrazine at DSA electrodes.
AB  - This paper presents the study of the electrochemical oxidation of the pesticide
      atrazine at a Ti/Ru(0.3)Ti(0.7)O(2) dimensionally stable anodes (DSA). The effect
      of using different supporting electrolytes (NaCl, NaOH, NaNO(3), NaClO(4),
      H(2)SO(4) and Na(2)SO(4)) during the galvanostatic electrolysis of atrazine was
      investigated. It was observed that the removal of atrazine and total organic
      carbon (TOC) was only achieved at appreciable rates when NaCl was used as the
      supporting electrolyte, due to the oxidising species formed in this electrolyte
      (e.g. ClO(-)). Variation of the NaCl concentration demonstrated that, although
      only low concentrations of NaCl are necessary to result in the complete removal
      of atrazine in solution, TOC removal is almost linearly dependent on the quantity
      of NaCl in solution. Examination of the applied current density indicates that
      the efficiency of TOC removal reaches a maximum at 60 mA cm(-2). Testing of
      alternative electrode materials containing SnO(2) did not improve the efficiency
      of atrazine removal in Na(2)SO(4), but in NaCl a small increase was observed.
      Overall there appears to be no great advantage in using SnO(2)-containing
      electrodes over the Ti/Ru(0.3)Ti(0.7)O(2) electrode.

PMID- 16621260
TI  - Reactivity of waste generated during lead recycling: an integrated study.
AB  - Lead consumption in Europe is 2.054 M tonnes/year, more than 70% of which is
      produced by recycling and, more specifically, the recycling of car batteries.
      This industry is jeopardised by the method employed so far, recycling by alkaline
      fusion, because the treatment produces 200,000 tonnes of toxic and unstable slag.
      The study presented here attempts to clarify the approach and the combined tools
      employed (mineralogy, chemistry, leaching, thermodynamics), to construct a
      coherent physicochemical model of slag behaviour. The model was then used to
      carry out sensitivity analyses with various landfill scenarios, and to propose
      adjustments to the process to recover the residual heavy metals and to upgrade as
      secondary raw products the co-products generated by the inerting of the slag.

PMID- 16621261
TI  - Use of EAF dust as heterogeneous catalyst in Fenton oxidation of PCP contaminated
      wastewaters.
AB  - In this study, chemical oxidation tests using H2O2 were performed on a solution
      contaminated with 100 mg l(-1) of pentachlorophenol (PCP). The effectiveness of
      electric arc furnace dust and hematite as heterogeneous catalysts was evaluated.
      Reactions were conducted at pH 2 for 24 h. Either H2O2 stabilized with KH2PO4 or
      un-stabilized H2O2 was used. Total organic carbon (T.O.C.) removal and chloride
      release from PCP molecule were monitored. Results showed that the maximum removal
      yields for electric arc furnace (EAF) dust (49.2% T.O.C., 56.7% Cl) were achieved
      when H2O2:PCP ratio was 10:1 and Fe:H2O2 = 1:5 for unstabilized H2O2 and when
      H2O2:PCP = 10:1 and Fe:H2O2 = 1:1 for stabilized H2O2 (48% T.O.C., 60.6% Cl). The
      maximum yield using hematite (45.2% T.O.C., 55.2% Cl) was obtained when H2O2:PCP
      ratio was 10:1 and Fe:H2O2 was 1:2. When EAF dust was used and Fe:H2O2 > 1:5, Cl
      release was higher than the one expected from T.O.C. removal.

PMID- 16621262
TI  - Determination of performance of non-ideal aluminized explosives.
AB  - Non-ideal explosives can have Chapman-Jouguet (C-J) detonation pressure
      significantly different from those expected from existing thermodynamic computer
      codes, which usually allows finding the parameters of ideal detonation of
      individual high explosives with good accuracy. A simple method is introduced by
      which detonation pressure of non-ideal aluminized explosives with general formula
      C(a)H(b)N(c)O(d)Al(e) can be predicted only from a, b, c, d and e at any loading
      density without using any assumed detonation products and experimental data.
      Calculated detonation pressures show good agreement with experimental values with
      respect to computed results obtained by complicated computer code. It is shown
      here how loading density and atomic composition can be integrated into an
      empirical formula for predicting detonation pressure of proposed aluminized
      explosives.

PMID- 16621263
TI  - Removal of Cu(II) ions by activated poplar sawdust (Samsun clone) from aqueous
      solutions.
AB  - In this work, adsorption of Cu(II) ions on sawdust (SD) and activated sawdust
      (ASD) has been studied by using batch adsorption techniques. The equilibrium
      adsorption level was determined to be a function of the pH, initial Cu(II)
      concentration, and adsorbent dosage. The equilibrium nature of Cu(II) adsorption
      has been described by the Freundlich and Langmuir isotherms. The experimental
      adsorption data were fitted to the Langmuir adsorption model both sawdust and
      activated sawdust. The equilibrium capacity of sawdust and activated sawdust were
      5.432 and 13.495 mg copper per g adsorbent, respectively at room temperature and
      natural pH. The maximum adsorption capacity was obtained at the maximum zeta
      potential value that -74.5 mV (pH 5) for activated sawdust and at -48.4 mV (pH 4)
      for sawdust. It was observed that activated sawdust was a suitable adsorbent than
      sawdust for removal of Cu(II) from aqueous solutions.

PMID- 16621264
TI  - In situ oil/water separation using hydrophobic-oleophilic fibrous wall: a lab
      scale feasibility study for groundwater cleanup.
AB  - Kapok, a natural plant fiber, possesses excellent hydrophobic-oleophilic
      characteristics. Its innovative use as hydrophobic-oleophilic wall that allows
      permeation of oil but not water into an oil recovery well is proposed. Its
      performance was investigated through laboratory experiments, in which diesel was
      used as the experimental oil. A two-dimensional hydraulic flume was setup to
      physically model the oil/water separation by the kapok wall. The influences of
      packing density, kapok wall thickness and oil thickness on the oil recovery rate
      were examined. The oil permeability of the packed kapok decreased from 0.0165 cm2
      at 34 g/L packing density to 0.0038 cm2 at 70 g/L packing density. The kapok wall
      exhibited complete rejection of water while allowed oil to permeate through. The
      excellent oil/water separation by the kapok wall was due to surface interaction
      between the kapok fibers and the oil, which resulted in spontaneous penetration
      and permeation of the oil through the kapok wall. The oil recovery rate increased
      with thickness of the oil layer in the feed stream. When the oil thickness
      exceeded 60 mm, a constant flux of 3.8-5.0, 3.2-3.3 and 2.5-2.7 L/(m2 min) could
      be achieved by the kapok wall of 55-, 75- and 95-mm thick, respectively, under
      the natural pressure gradient. The kapok wall could be reused for several
      wetting/drying cycles, and only lost 27% of its initial oil permeability.

PMID- 16621265
TI  - Enhanced malachite green removal from aqueous solution by citric acid modified
      rice straw.
AB  - In this paper, rice straw was thermochemically modified with citric acid (CA) as
      esterifying agent. Two introduced free carboxyl groups of esterified rice straw
      were further loaded with sodium ion to yield potentially biodegradable cationic
      sorbent. In order to investigate the effect of chemical modification on the
      cationic dye sorption of rice straw, the removal capacities of native and
      modified rice straw sorbing a cationic dye (malachite green) from aqueous
      solution were compared. The effects of various experimental parameters (e.g.
      initial pH, sorbent dose, dye concentration, contact time) were investigated. For
      modified rice straw (MRS), the malachite green (MG) removal percentage came up to
      the maximum value beyond pH 4. For the 250 mg/l of MG solution, the 1.5 g/l or up
      of MRS could almost completely remove the dye from aqueous solution. Under the
      condition of 2.0 g/l sorbent used, the percentage of MG sorbed on MRS kept above
      93% over a range from 100 to 500 mg/l of MG concentration. The sorption isotherms
      fitted the Langmuir or Freundlich models. The sorption equilibriums were reached
      at about 10 h. The sorption processes followed the pseudo-first-order rate
      kinetics. After chemical modification, the intraparticle diffusion rate constant
      (k(id)) was obviously increased. The results in this study indicated that MRS was
      an excellent sorbent for removal of MG from aqueous solution.

PMID- 16621266
TI  - Removal of copper from aqueous solution using Ulva fasciata sp.--a marine green
      algae.
AB  - Batch adsorption experiments were carried out for the removal of copper from its
      aqueous solution using Ulva fasciata sp. a marine green algae as adsorbent. The
      adsorption of Cu(II) by Ulva fasciata sp. was investigated as a function of pH,
      contact time, initial Cu(II) and adsorbent concentrations and adsorbent size.
      About 0.1 g of Ulva fasciata sp. was found to be enough to remove 95% of 20 mg/L
      copper from 30 mL aqueous solution in 20 min. The optimum pH value was found to
      be 5. The dynamic data fitted to the pseudo-second order kinetic model. The
      Langmuir and Freundlich adsorption models were applied to describe the
      equilibrium isotherms and the isotherm constants were determined. The
      experimental adsorption data were fitted to the Langmuir adsorption model. The
      maximum adsorption capacity was 26.88 mg/g. The applicability of Lagergren
      kinetic model was also investigated.

PMID- 16621267
TI  - Evaluation of engineering properties for the use of leached brown coal ash in
      soil covers.
AB  - The need to engineer cover systems for the successful rehabilitation or
      remediation of a wide variety of solid wastes is increasing. Some common
      applications include landfills, hazardous waste repositories, or mine tailings
      dams and waste rock/overburden dumps. The brown coal industry of the Latrobe
      Valley region of Victoria, Australia, produces significant quantities of coal ash
      and overburden annually. There are some site-specific acid mine drainage (AMD)
      issues associated with overburden material. This needs to be addressed both
      during the operational phase of a project and during rehabilitation. An
      innovative approach was taken to investigate the potential to use leached brown
      coal ash in engineered soil covers on this overburden dump. The basis for this is
      two-fold: first, the ash has favourable physical characteristics for use in cover
      systems (such as high storage capacity/porosity, moderately low permeability, and
      an ability to act as a capillary break layer generating minimal leachate or
      seepage); and second, the leachate from the ash is mildly alkaline (which can
      help to mitigate and reduce the risk of AMD). This paper will review the
      engineering issues involved in using leached brown coal ash in designing soil
      covers for potentially acid-forming overburden dumps. It presents the results of
      laboratory work investigating the technical feasibility of using leached brown
      coal ash in engineered solid waste cover systems.

PMID- 16621268
TI  - Trapping heavy metals by using calcium hydroxyapatite and dielectrophoresis.
AB  - We propose a novel technique for the removal of heavy metal waste from
      contaminated water. Our method consists in using dielectrophoresis (DEP) to trap
      hydroxyapatite (HAP) particles of 1 microm size in water after they have adsorbed
      heavy metal (Pb, Zn, Cu, Co and Cr). Although HAP can adsorb heavy metals in
      water and as such offers great promise as a waste-cleaning tool , one of the
      current challenges is the efficient removal of the HAP particles once they have
      adsorbed the heavy metals. We show in this paper that DEP can be used to
      concentrate such particles in certain regions, thus rendering the rest of the
      solution volume nearly free of contaminated particles. We present here both
      experimental and numerical results for suspensions at low concentrations.

PMID- 16621269
TI  - Synthesis of nano titania particles embedded in mesoporous SBA-15:
      characterization and photocatalytic activity.
AB  - Supported nanocrystalline titanium dioxide (TiO2) has been prepared by a post
      synthesis step via Ti-alkoxide hydrolysis through the use of mesoporous SBA-15
      silica. TiO2/SBA-15 composites with various TiO2 loading have been prepared and
      characterized by X-ray diffraction, nitrogen adsorption, Fourier transform
      infrared spectroscopy and diffusive reflective UV-vis spectroscopy. The addition
      of mesoporous SBA-15 prevents the anatase to rutile phase transformation and the
      growth of crystal grain. TiO2 did not block the SBA-15 pores, and their surface
      was fully accessible for nitrogen adsorption. Calcination in air of the
      composites up to 800 degrees C did not change the nanocrystal phase and slightly
      increased the domain size from 5.0 to 7.5 nm, indicating that the anatase TiO2
      grains in the mesostructures have a relatively high thermal stability and proper
      pore diameter allows controlling the size of obtained titania particles. The
      TiO2/SBA-15 composites prepared by this study showed much higher photodegradation
      ability for methylene blue (MB) than commercial pure TiO2 nanoparticles P-25.
      Experimental results indicate that the photocatalytic activity of titania/silica
      mixed materials depends on the adsorption ability of composite and the
      photocatalytic activity of the titania, and there is an optimal ratio of Ti:Si,
      too high or low Ti:Si ratio will lower the photodegradation ability of the
      composites.

PMID- 16621270
TI  - Separation and recovery of lead from a mixture of some heavy metals using
      Amberlite IRC 718 chelating resin.
AB  - A weakly acidic ion exchanger resin containing the iminodiacetate group has been
      used to separate and recover metal ion from their mixtures. Batch and column
      methods were applied for the separation studies. Previous study on the kinetics
      and thermodynamics shows that the selectivity of this resin for transition metals
      was quite high as compared to that of alkaline earth metals. The efficiency of
      this resin in different experimental conditions was established and because of
      the large difference in the distribution coefficient values separation of the
      metal ions from their mixture was performed.

PMID- 16621271
TI  - Phosphate removal from aqueous solutions using raw and activated red mud and fly
      ash.
AB  - The effect of acidification and heat treatment of raw red mud (RM) and fly ash
      (FA) on the sorption of phosphate was studied in parallel experiments. The result
      shows that a higher efficiency of phosphate removal was acquired by the activated
      samples than by the raw ones. The sample prepared by using the RM stirred with
      0.25 M HCl for 2h (RM0.25), as well as another sample prepared by heating the RM
      at 700 degrees C for 2h (RM700), registered the maximum removal of phosphate (99%
      removal of phosphate). This occurred when they were used in the phosphate
      sorption studies conducted at pH 7.0 and 25 degrees C with the initial PO(4)(3-)
      concentration of 155 mg P/l. The FA samples treated in the same way described
      above can achieve 7.0 and 8.2 mg P/l phosphate removal for FA0.25 and FA700
      respectively, corresponding to 45.2% and 52.9% removal. The activated materials
      performed higher phosphate removal over broader pH range compared with the raw
      ones. The influences of various factors, such as initial pH and initial phosphate
      concentration on the sorption capacity were also studied in batch equilibration
      technique. Solution pH significantly influenced the sorption. Each sample
      achieved the maximal removal of phosphate at pH 7.0. The amount of phosphate
      removal increased with the solute concentration. The Freundlich and Langmuir
      models were used to simulate the sorption equilibrium. The results indicate that
      the Langmuir model has a better correlation with the experimental data than the
      Freundlich model.

PMID- 16621272
TI  - A soft-solution process for recovering rare metals from metal/alloy-wastes by
      grinding and washing with water.
AB  - We have developed a novel process for recovering metals from alloy-wastes by
      using a mechanochemical (MC) reaction. The process consists of co-grinding both
      alloy and polyvinyl chloride (PVC) samples, followed by washing with water and
      filtration. The co-grinding of the wastes causes a solid-state MC reaction to
      form metal chlorides and hydrocarbon in the product. The former products are
      soluble in water, so they can be recovered from the wastes by washing with water,
      followed by filtration. The PVC waste plays a significant role as a chlorine
      source in the MC reaction. After filtration, the solid residue can be used as a
      fuel, due to the absence of chlorine in the product, and the filtrate is
      subjected to hydrometallurgical process to extract metals from the solution.

PMID- 16621273
TI  - Pure, single phase, high crystalline, chamfered-edge zeolite 4A synthesized from
      coal fly ash for use as a builder in detergents.
AB  - Single phase chamfered-edge zeolite 4A samples in pure form with a high
      crystallinity were synthesized by applying step-change of synthesis temperature
      during hydrothermal treatment of coal fly ash. The calcium binding capacity of
      these zeolite 4A samples (prepared from coal fly ash) and the commercial
      detergent grade zeolite 4A were tested for usage as a detergent builder. The
      results show that these zeolite 4A samples behaved similarly as the commercial
      one in removing calcium ions during the washing cycle. Moreover, from the
      leaching tests (evaluation of toxicological safety), the results show that these
      zeolite 4A samples leached the same elements (Sb, As, Se and Tl) as the
      commercial one with the concentrations in the same order of magnitude. This shows
      that the toxicological effect of the coal fly ash converted zeolite 4A was not
      worse than that of the commercial sample. Finally, economic and environmental
      aspects of converting coal fly ash to useful products were discussed.

PMID- 16621274
TI  - The effect of salinity conditions on kinetics of trichloroethylene biodegradation
      by toluene-oxidizing cultures.
AB  - This study investigates the effect of salt (NaCl) conditions on the
      biodegradations of trichloroethylene (TCE) by mixed cultures enriched on toluene.
      Two cultures were separately cultivated in this investigation, involving culture
      LHTO4, cultivated with freshwater and culture HHTO4, cultivated with 3.5% (w/v)
      NaCl solution. Batch tests were conducted to elucidate the degradations of
      toluene, TCE and a mixture of toluene and TCE by cultures LHTO4 at salinities of
      0, 2 and 3.5% and by HHTO4 at salinity of 3.5%. The measurements were analyzed
      with microbial kinetics. The results show that for culture LHTO4 in the resting
      cells, when the transient salinities increased from 0 to 3.5%, the maximum
      specific rate of TCE degradation, k(TCE), declined from 2.28 to 1.45 d(-1), and
      the observed TCE transformation capacity, T(c,obs), decreased from 0.060 to 0.036
      mgTCE/mgVSS. In the presence of toluene, TCE degradation was more inhibited by
      toluene (inhibition coefficients, K(I,TOL) were 0.8, 2.2, and 0.96 mg/L for
      salinity 0, 2, and 3.5%, respectively) than toluene degradation was by TCE
      (K(I,TCE) were 14, 5.8, and 1000 mg/L for salinity 0, 2, and 3.5%, respectively).
      Under long-term salinity stress, the culture HHTO4 maintained its capacity to
      utilize toluene but lost its effectiveness in the cometabolic transformation of
      TCE: k(TCE) fell to 0.25 d(-1) and T(c,obs) dropped to 0.024 mgTCE/mgVSS. This
      work reveals that the degradation of TCE by toluene-oxidizing cultures under
      saline conditions can be best described by the chosen kinetic equations and
      experimentally estimated constants, which can thus be used to lay a foundation
      for the rational design of biological processes to remove TCE from saline
      solutions.

PMID- 16621275
TI  - Monitoring of leachate at a test road using treated fly ash from municipal solid
      waste incinerator.
AB  - A treatment process for municipal solid waste incinerator fly ash has been
      jointly developed by the Universite Libre in Brussels and the Solvay company.
      This experimental process has led to an experimental project with a multi
      disciplinary team from Solvay along with several companies and organisations,
      plus support from the ADEME agency. After a laboratory assessment of the treated
      fly ash (TFA), its environmental properties and the optimal fields of application
      in road construction, as part of the Revasol project, a full-scale analysis was
      organised for both environmental and mechanical purposes. A test section using
      TFA was designed in order to collect percolation water; TFA was used as a road
      base component (a cement-bound graded aggregate containing 12% TFA). A reference
      section with the same structure was also built using natural materials. After a
      description of the treatment process and the test road design, the main TFA
      characteristics are presented. Then, the environmental behaviour of both sections
      over a 1-year period following construction is detailed: infiltration, leachate
      quality, cumulative release. This monitoring effort highlights not only the
      evolution in TFA behaviour, but also the general permeability of the road
      structure to various external influences.

PMID- 16621276
TI  - Catalytic oxidation of benzene using DBD corona discharges.
AB  - Plasma oxidation of benzene (C(6)H(6)) in oxygen and nitrogen was investigated
      using a dielectric barrier discharge (DBD) reactor with or without MnO2 or TiO2
      at atmospheric pressure and without external heating except plasma heating. An
      alternative current power supply was used to generate corona discharges for the
      plasma oxidation. The energy density was controlled under 200 J/L to keep an
      increase in gas temperature less than 167 K. C(6)H(6) was oxidized to carbon
      monoxide (CO) and dioxide (CO(2)). Typically, the energy efficiency at an energy
      density of 92J/L was about 0.052, 0.039, and 0.024 mol/kWh with MnO2, TiO2, and
      without MnO2 and TiO2, respectively. Benzene oxidation mechanism was mentioned. A
      comparison on energy efficiency as a function of initial concentration of
      hydrocarbons, inorganic sulphur compounds, and chloro (fluoro and bromo) carbons
      was given.

PMID- 16621277
TI  - Removal of aqueous lead ions by hydroxyapatites: equilibria and kinetic
      processes.
AB  - The capacity of hydroxyapatite (HAp) to remove lead from aqueous solution was
      investigated under different conditions, namely initial metal ion concentration
      and reaction time. The sorption of lead from solutions containing initial
      concentrations from 0 to 8000 mg/L was studied for three different HAp powders.
      Soluble Pb and Ca monitoring during the experiment allows characterizing the
      mechanism of lead uptake. Dissolution of calcium is followed by the formation of
      a solid solution, Pb(x)Ca(10-x)(PO4)6(OH)2, with a Ca/P ratio decreasing
      continuously. Langmuir-Freundlich classical adsorption isotherms modeled
      adsorption data. The adsorption capacities calculated from this equation vary
      from 330 to 450 mg Pb/g HAp for the different solids. Modeling of the sorption
      process allows to determine theoretical saturation times and residual lead
      concentrations at equilibrium.

PMID- 16621278
TI  - Distribution of vanadium(V) species between soil and plants in the vicinity of
      vanadium mine.
AB  - The distribution of vanadium(V) species between soil and plants around the
      vanadium mine have been studied. The mine dam spilled water around this area
      after collapsing some time ago. V(V) species were determined by electrothermal
      atomic absorption spectrometry (ETAAS) after leaching of vanadium(V) compounds
      with 0.1M of Na2CO3, with a limit of detection 0.2 microg g(-1). The validity of
      V(V) determination had been confirmed by the spike recovery and of the total
      amount of vanadium by the analysis of CRM's with good correspondence of found to
      certified values. The concentration of V(V) species were found to be in the range
      of 620-1680 microg g(-1) in soil and 4-6 microg g(-1) in grass samples,
      respectively. The total amount of vanadium in soil varied from 1570 to 3600
      microg g(-1) and from 8 to 13 microg g(-1) in grass. The results indicate that
      considerable amount of vanadium (about 50%) in soils and plants is present as
      V(V) species.

PMID- 16621279
TI  - Stabilization of chromium ore processing residue (COPR) with nanoscale iron
      particles.
AB  - Laboratory batch experiments were conducted on heavily contaminated groundwater
      and chromium ore processing residue (COPR) samples to determine the rate and
      extent of hexavalent chromium [Cr(VI)] reduction and immobilization by nanoscale
      iron particles. Laboratory synthesized nanoscale iron particles (<100 nm,
      specific surface area 35 m(2)/g) were used for this work. Groundwater
      ([Cr(VI)]=42.83 +/- 0.52 mg/L, pH 11.0+/-0.5) and COPR samples ([Cr(VI)] = 3280
      +/- 90 mg/kg) were collected from an industrial site in New Jersey. Cr(VI) in the
      water and COPR samples was quickly reduced and precipitated out of the aqueous
      solution. The surface area normalized reaction rate constant of Cr(VI) reduction
      by nanoscale iron particles was 0.157 +/- 0.018 mg m(-2) min(-1), about 25 times
      greater than that by iron powders (100 mesh). One gram of nanoparticles can
      reduce 84.4-109.3mg Cr(VI) in the groundwater and 69.3-72.7 mg Cr(VI) in the
      COPR. This reduction capacity is 50-70 times greater than that of iron powders
      under the same experimental conditions.

PMID- 16621280
TI  - Photo-Fenton discoloration of the azo dye X-3B over pillared bentonites
      containing iron.
AB  - Both Fe pillared bentonite (Fe-B) and Al-Fe pillared bentonite (Al/Fe-B) were
      prepared and used as heterogeneous catalysts for the photo-Fenton discoloration
      of azo dye X-3B under UV irradiation. The catalysts were characterized by XRD,
      BET and TEM. The effects of solution pH, H(2)O(2) concentration, dye
      concentration and catalyst loading on the rate of discoloration were investigated
      in detail. The results indicate that the Fe-B and Al/Fe-B have high BET surface
      area (114.6 and 194.2 m(2)/g, respectively). Both the heterogeneous photo-Fenton
      processes employing the Fe-B or the Al/Fe-B as catalyst exhibit higher photo
      catalytic activity compared to their corresponding homogeneous photo-Fenton
      process. The amount of Fe ions leached from the Al/Fe-B into the solution is much
      lower than that leached from the Fe-B during the reaction process.

PMID- 16621281
TI  - Kisspeptin immunoreactive cells of the ovine preoptic area and arcuate nucleus co
      express estrogen receptor alpha.
AB  - Kisspeptins are peptide ligands of the G protein-coupled receptor GPR54, recently
      shown to be essential to reproductive function. We have raised specific rabbit
      antisera against a highly conserved 10 amino acid-amidated peptide (kp10) common
      to all kisspeptin isoforms isolated so far and mapped the distribution of kp10
      immunoreactive (ir) cells in the ovine hypothalamus. Kp10-ir cells were
      predominant in the caudal arcuate nucleus, the dorsomedial nucleus and the medial
      preoptic area. Numerous varicose kp10-ir fibers were found in the preoptic area
      where GnRH neurons reside and in the median eminence, seemingly projecting around
      small capillaries in its external zone. Within the caudal arcuate nucleus, nearly
      all kp10-ir cells showed an intense estradiol receptor alpha immunofluorescent
      signal compared with approximately half of kp10-ir cells in the preoptic area.
      The pattern of distribution of kp10 immunoreactivity in the hypothalamus suggests
      a role for kisspeptin in the estrogen-dependent regulation of GnRH and LH
      secretion in the ewe.

PMID- 16621282
TI  - Comment on Goubert et al.: facing others in pain: the effects of empathy. Pain
      2005;118:285-8.

PMID- 16621284
TI  - Human outbreak of trichinellosis in the Mediterranean island of Sardinia, Italy.
AB  - Trichinella sp. infection has been documented in both humans and animals in most
      Mediterranean countries, yet in the past 60 years no infections have been
      reported on the Mediterranean islands. We describe the first outbreak of
      Trichinella sp. infection to have been reported on the island of Sardinia. The
      outbreak occurred in two villages in 2005 and involved 11 persons who had eaten
      raw sausages made from the same free-ranging sow. All 11 persons developed signs
      and symptoms of trichinellosis and seroconverted within 48 days of consuming the
      infected meat. The etiological agent was Trichinella britovi. Sardinia, like all
      Mediterranean islands, had been considered to be Trichinella-free. The present
      report, together with a recent report of T. britovi infection in animals on the
      nearby island of Corsica (France), raises questions as to the validity of the
      concept of Trichinella-free areas or regions.

PMID- 16621283
TI  - Lymphocyte apoptosis in the inflammatory reaction around Taenia solium
      metacestodes in porcine cysticercosis.
AB  - In the current research, we report apoptosis of lymphocytes in the inflammatory
      reaction around metacestodes in muscle tissue from cysticercotic pigs. Two
      events, high metacestode viability (100%) and high cysteine protease activity
      were found to be closely related to a high phosphatydilserine expression by
      inflammatory lymphocytes (56%). Testing the RPMI medium used for washing away
      inflammatory cells from metacestodes with 100% viability, with the fluorescent
      substrate Z-Phe-Ala-AFC for measuring cysteine protease activity, significant
      fluorescent values were found. In contrast, tests performed with RPMI medium used
      for washing away inflammatory cells from metacestodes with 90% viability or less,
      showed low fluorescence values. Flow cytometry analyses of inflammatory cells
      obtained from four naturally cysticercotic pigs, and stained with Annexin-V/PI,
      showed lymphocytes expressing phosphatidylserine with values of 0, 6, 41 and 56%
      on their outer surfaces. Electron microscopy studies of inflammatory cells from
      metacestodes with 100% viability, showed lymphocytes with strangled and
      fragmented nuclei, and heterochromatin displaced to the nuclear periphery. In
      addition, DNA from these cells showed fragmentation in electrophoresis assays.
      Apoptosis of lymphocytes in the inflammatory reaction around Taenia solium
      metacestodes, might have been induced by the parasite cysteine protease, and may
      be involved in impairing cell-mediated immune responses in human and porcine
      cysticercosis.

PMID- 16621285
TI  - Detection of Ehrlichia chaffeensis in Brazilian marsh deer (Blastocerus
      dichotomus).
AB  - Ehrlichia chaffeensis was detected for the first time in blood samples from
      Brazilian marsh deers (Blastocerus dichotomus) captured in the marshes of Parana
      River in Southeast Brazil in 1998. Seven EDTA-blood samples from deers were
      analyzed by PCR and nested PCR for presence of Ehrlichia chaffeensis, Ehrlichia
      ewingii, Ehrlichia canis, Neoriickettsia risticii, Anaplasma phagocytophilum and
      Anaplasma marginale. Three samples showed positive reactions for E. chaffeensis
      and Anaplasma marginale. None contained detectable A. phagocytophilum, E.
      ewingii, E. canis or Neorickettsia risticii DNA. In Brazil, the wild marsh deer
      may be a natural reservoir of the agents that cause human monocytotropic
      ehrlichiosis and ruminant erythrocytic anaplasmosis.

PMID- 16621286
TI  - Seroepidemiological survey on canine leishmaniasis among dogs from an urban area
      of Brazil.
AB  - A cross-sectional seroepidemiological survey on canine leishmaniasis among pet
      dogs was carried out in an urban area in the State of Pernambuco (Brazil) where
      human cases of visceral leishmaniasis have sporadically been reported. Using an
      indirect fluorescent antibody test, anti-Leishmania antibodies were detected in
      130 out of 322 dogs, confirming previous exposure to Leishmania parasites. The
      overall seroprevalence found was 40.3% (95% confidence interval: 34.9-45.9). Data
      analysis revealed that serological positivity was statistically associated with
      male (chi2=20.60, P-value=0.000) and juvenile dogs (chi2=4.24, P-value=0.039).
      Furthermore, it was observed that 85.3% of all seropositive dogs showed no
      clinical signs of leishmaniasis. The results showed a high seroprevalence of anti
      Leishmania antibodies among dogs from an urban area of Pernambuco - with a large
      proportion of asymptomatic seropositive dogs - indicating that the prevalence of
      Leishmania infection in this area has been underestimated.

PMID- 16621287
TI  - Studies on the interaction between Salmonella enterica ser. Typhimurium and
      intestinal helminths in pigs.
AB  - Concomitant infections with helminths and bacteria may affect the course and the
      resulting disease outcome of the individual infections. Salmonella,
      Oesophagostomum, Trichuris and Ascaris coexist naturally in pig herds in Denmark,
      and possible interactions were studied. Pigs in one experiment were trickle
      infected with low or moderate dose levels of Oesophagostomum spp. and challenge
      infected with S. Typhimurium. In another experiment, pigs were inoculated with S.
      Typhimurium followed by a challenge exposure to either Oesophagostomum, Trichuris
      or Ascaris. Enhancement of the Salmonella infection was not demonstrated in
      either experiment. The helminth effect on the pigs was modest and may explain the
      lack of influence on the Salmonella infection. A previous experiment with a
      larger Oesophagostomum infection level resulted in enhancement of the S.
      Typhimurium infection. A dose dependency of the interaction is therefore
      suggested. However, the relatively high worm burdens in the present study suggest
      that infection with these common pig helminths does generally not influence the
      course of concurrent S. Typhimurium infections under natural conditions.

PMID- 16621288
TI  - A nationwide survey on seroprevalence of Neospora caninum infection in beef
      cattle in Uruguay.
AB  - Bovine abortions due to Neospora caninum infection have been reported worldwide
      and its economic impact on the beef industry has been acknowledged as a problem.
      Uruguay has the largest export value of beef per acre in South America. However,
      no data on the prevalence of N. caninum infection have been available in this
      country. The objective of this study was to estimate the prevalence and
      distribution of N. caninum infection in beef cattle in Uruguay through a
      nationwide survey. A two stage sampling design was used with farms being selected
      in stage one and animals being selected in stage two. A brief questionnaire was
      administered on each farm. Seroprevalence of N. caninum in 4444 beef cattle from
      229 farms in all the counties, except Montevideo, of Uruguay was determined by an
      ELISA. The data were then analyzed to identify associations between infection and
      variables such as type of animal (cow or heifer), herd size, use of veterinary
      advice, productivity of the soil in relation to the national average, use of
      improved grass, use of mineral salts, use of supplemental feed, and presence of a
      dog(s) on the farm. The estimated proportion of positive farms for all the beef
      cattle operations was 69.2% (95% confidence interval [CI], 53.7-84.7). The
      overall cattle seroprevalence was estimated as 13.9% (95% CI, 11.6-16.3). The
      prevalence estimation by animal category was 14.3% (95% CI, 11.4-17.2) for beef
      cows and 12.9% (95% CI, 10.0-15.8) for beef heifers. There was no significant
      difference in the estimated prevalence between the two animal types. There was no
      significant difference in the animal level prevalence of N. caninum infection
      among different herd sizes. None of the herd demographic or management variables
      was significantly associated with the seropositivity to N. caninum infection. In
      conclusion, these results show that N. caninum infection is common among beef
      herds across Uruguay. Since the beef industry is one of the key industries in
      Uruguay, the economic effect and risk factors of N. caninum infection among beef
      cattle in this country should be further evaluated in the near future.

PMID- 16621289
TI  - Detection of Cryptosporidium felis and Giardia duodenalis Assemblage F in a cat
      colony.
AB  - Eighteen cats, 3-6 months of age, bred and housed in a closed colony, were
      transferred from that colony and placed in separate stainless steel cages in a
      building designed for housing animals. At daily intervals, feces were collected
      from the litter pans in each cage, pans and cages were cleaned, and fresh food
      and water were provided. Beginning 4 weeks after the transfer, oocysts of
      Cryptosporidium were detected in the feces of two cats by brightfield microscopy.
      For the following 21 days, with minor exceptions, feces from each cat were
      collected daily and examined by immunofluorescence microscopy and by molecular
      methods that included DNA extraction, 18S rDNA gene amplification, and DNA
      sequence analysis. Within those 22 days, every cat was found to be infected with
      Cryptosporidium felis and excreted oocysts for 6-18 days. Eight of these 18 cats
      also excreted cysts of Giardia duodenalis Assemblage F, a genotype found only in
      cats. Six Giardia infections were concurrent during part of the patency with C.
      felis infections. Neither diarrhea nor other signs of illness were observed in
      any of the cats during this time. Because C. felis is zoonotic these findings
      suggest that care should be taken by veterinary health care providers and others
      in close contact with cats, even when cats appear healthy and asymptomatic.

PMID- 16621290
TI  - Segregation of natural and experimental gastrointestinal nematode infection in F2
      progeny of susceptible Suffolk and resistant Gulf Coast Native sheep and its
      usefulness in assessment of genetic variation.
AB  - Gastrointestinal nematode parasitism is a concern to small ruminants worldwide.
      Productivity has been compromised because such nematodes, particularly Haemonchus
      contortus, have developed resistance to available anthelmintics. Some sheep
      breeds and lines within breeds are relatively resistant to infection, a trait
      that may be useful for developing control strategies. Suffolk sheep, which are
      susceptible to infection, were crossed with Gulf Coast Native sheep, which are
      more resistant to infection, to produce F1 progeny. F1 rams were bred to F1 ewes
      which produced 227 F2 offspring. These F2 offspring were evaluated for
      variability in infection levels, based on fecal egg count (FEC) and blood packed
      cell volume (PCV), under two natural infection conditions (one at weaning and
      another after a summer grazing period) and one experimental infection. The range
      of both FEC and PCV was large for all three infection periods with annual
      variation. Overall, the range for the three infection periods, respectively, were
      167-149,933, 0-31,400 and 17-114,667 eggs per gram (EPG) of feces and 8.7-37.0%,
      7.3-33.0% and 8.3-36.0%. This segregation of infection is what would be expected
      of F(2) progeny from susceptible and resistant parent breeds. Heritabilities of
      FEC and PCV for the three infection periods, respectively, were 0.15, 0.29 and
      0.12, and 0.11, 0.22 and 0.12. Based on segregation of infection, larger
      heritabilities and maternal environment effects that declined after weaning, the
      summer natural infection was probably the best model for assessing genetic
      variation.

PMID- 16621291
TI  - Agricultural restructuring and gastrointestinal parasitism in domestic ruminants
      on the rangelands of Kazakhstan.
AB  - In order to evaluate the epidemiology of parasitism in farmed ruminants in the
      changed agricultural context in Kazakhstan, 505 cattle, sheep and goats were
      surveyed for gastrointestinal parasitism using coprological examination, and a
      further thirty sheep and four goats using post mortem extraction of helminths.
      The dominant helminth genera were Marshallagia, Nematodirus and Trichostrongylus.
      Haemonchus was also present. Faecal egg counts were low (mean abundance 0-115
      eggs per gram in different groups), and there was no relationship between faecal
      egg density and body condition score. Eggs of Nematodirus spp. were more common
      in sheep less than 1 yr of age, whereas those of the Trichostrongylidae were
      generally more common in adult sheep. Based on faecal egg counts, sheep grazing
      on common land close to permanent human settlements were generally no more
      heavily infected than those grazing the remote open plains. This could be due to
      a non-linear relationship between livestock numbers and stocking density. We
      suggest that cessation of strategic nematode control in the region following post
      Soviet agricultural reform was offset by a general reduction in stocking density,
      such that parasite burdens remained low. However, recovery in livestock numbers
      is likely to lead to increased levels of infection and production loss unless
      sustainable control strategies are put in place.

PMID- 16621292
TI  - In vitro entomopathogenic activity of Beauveria bassiana against Psoroptes spp.
      (Acari: Psoroptidae).
AB  - An indigenous strain (IHEM 18747) of Beauveria bassiana (Balsamo) Vuillemin
      (Deuteromycetes) was evaluated for its in vitro entomopathogenic activity against
      the parasitic mite Psoroptes ovis Hering (Acari: Psoroptidae) from rabbits. The
      following aspects were evaluated: (1) effects of conidial concentration on the
      viability of adult females; (2) influence of the infection on the fertility, and
      on the hatchability of eggs; (3) and transmission of infection between mites, and
      from contaminated surface. Adult females immersed into increasing concentrations
      of conidia (10(4)-10(9)conidia ml(-1)) showed a dose-related susceptibility. At
      the highest concentration of conidia, LT50 was 1.6 days while LT50 of the
      controls reached 5.8 days. The fungus was able to sporulate on the body surface
      and 100% of the mites were covered with mycelium after immersion in solutions
      containing 10(7)-10(9)conidia ml(-1). One hundred percent of healthy mites
      exposed to infected cadavers or surfaces acquired the infection (LT50 reached 1.9
      and 1.73 days, respectively, versus 6.1 and 5.1 days in controls, respectively).
      Egg laying was not reduced by the fungal infection but both the hatchability of
      the eggs and the life span of the emerging larvae were significantly reduced.
      Eggs directly infected with the fungus did not show reduced hatchability but the
      life span of the larvae was shortened. It is concluded that B. bassiana has a
      high entomopathogenic activity against Psoroptes spp. The in vivo use of this
      biocontrol agent against Psoroptes spp. in rabbit, sheep and cattle deserves
      further attention.

PMID- 16621293
TI  - Evaluation of enzyme-linked immunosorbent assays with recombinant antigens for
      the serodiagnosis of equine Babesia infections.
AB  - Two enzyme-linked immunosorbent assays (ELISA) with recombinant protein as
      antigens were evaluated by comparison with the indirect fluorescent antibody
      tests (IFAT) for the detection of specific antibodies to Babesia caballi and
      Babesia equi, respectively in 380 sera from experimentally infected, uninfected,
      and field horses. The high concordances of 92.4% (351/380) and 98.2% (373/380)
      between ELISA and IFAT for B. caballi and B. equi, respectively suggest that
      ELISA, especially for B. equi infection, could be alternative to the
      corresponding IFAT for serodiagnoses of equine piroplasmosis, although some
      improvements are required in ELISA for B. caballi.

PMID- 16621294
TI  - Ovicidal and larvicidal activity of Melia azedarach extracts on Haemonchus
      contortus.
AB  - Haemonchus contortus is responsible for severe economic losses in sheep and goat
      breeding in the Northeast of Brazil. However, the effectiveness of control is
      compromised due to anthelmintic resistance and misuse. In the search for natural
      anthelmintics, Melia azedarach L., a plant indigenous to India but now
      distributed throughout Brazil, was selected due to the reported anthelmintic
      properties of its seeds. The aim of this study was to evaluate the anthelmintic
      activity of the seed and leaf extracts of the Brazilian adapted plant and
      investigate the type of organic chemical compounds present in the most active
      extracts. The ovicidal and larvicidal activity of M. azedarach extracts on H.
      contortus was evaluated through egg hatching and larval development tests. Hexane
      and ethanol extracts of seeds and chloroform and ethanol extracts of leaves of M.
      azedarach were used in the tests. To perform the larval development test, feces
      of an animal free from parasites were mixed with third instar H. contortus larvae
      and extracts in several concentrations. The coprocultures were incubated for 7
      days at 30 degrees C, then the larvae were recovered and counted. LC50 was
      calculated by probits using the SPSS 8.0 program. The seed ethanol extract was
      the most active on eggs (LC50=0.36mgmL(-1)) and the leaf ethanol extract showed
      the best inhibition of larval development (LC50=9.18mgmL(-1)). Phytochemical
      analysis of the most active extracts revealed the presence of condensed tannins,
      triterpenes and alkaloids.

PMID- 16621296
TI  - Intentional burn injuries.

PMID- 16621295
TI  - Structural and cytochemical changes in the salivary glands of the Rhipicephalus
      (Boophilus) microplus (CANESTRINI, 1887) (Acari: Ixodidae) tick female during
      feeding.
AB  - This study describes the morphology of salivary glands of Rhipicephalus
      (Boophilus) microplus female ticks at beginning of feeding (24-48 h of
      attachment) and semi-engorged (4-5 days of attachment) to verify the degenerative
      characteristics of these organs and the secretory phase in which the process
      begins. At the beginning of feeding, secretion granules had been observed only in
      the cytoplasm of cells b, c1, c2, c4 (type II acinus) and d (type III acinus), as
      well as large nuclei with regular and preserved morphology. In the semi-engorged
      females the acini presented few normal cells, few partially preserved ones, and
      the remaining ones in several stages of degeneration, that is, with retraction
      and cytoplasmic vacuolization, and nuclei with chromatin in several stages of
      condensation, picnotic and/or in fragmentation. In type I acinus and in the
      excretory ducts of the studied glands, at both feeding stages, no degenerative
      characteristic was observed. In females of R. (B.) microplus, the salivary glands
      degenerate asynchronically and precociously when compared with those of others
      tick's species.

PMID- 16621298
TI  - Assessment of burn area: can we be too objective!

PMID- 16621297
TI  - Overexpansion technique in burn scar management.
AB  - Overexpansion techniques are useful in overcoming a shortage of donor site for
      expansion: the aim of the authors was to verify whether this technique should be
      chosen instead of serial expansions for creation of wider and more malleable
      flaps for reconstruction. From 1993 to May 2005 we have overexpanded 59 patients
      with burn scars. The patients always underwent reconstruction at least 2 years
      after complete healing. Almost any body region capable of expansion has been
      overexpanded. The technique is illustrated here in the reconstruction of scalp,
      neck, trunk and thigh. Tissue expander original volume ranged from 450 to 800 cc:
      the silicon implant shape was both round and rectangular. Mean overinflation was
      3.6 times beyond the stated vendor's maximum volume. The principle ratios were
      performed in the trunk (4.375) and in the lower extremities (4.125). The largest
      volume instilled in a single tissue expander was 3,500 cc. Overall expansion
      length was on average 172.6 days (range: 101-248). All patients were compliant
      with inflation once a week. The reconstructions were planned as the expansion of
      a transposition or an advancement flap. All patients had completion of their
      reconstruction with satisfactory resolution of their problem: complications
      occurred in three of all hyperinflated prostheses. Tissue overexpansion, if
      carefully planned and conducted, allows the completion of reconstruction in one
      stage. Instead of serial expansions, it enhances patient compliance and reduces
      cost.

PMID- 16621299
TI  - Phenol burn.

PMID- 16621300
TI  - The Acticoat glove-an effective dressing for the completely burnt hand: how we do
      it.
AB  - The choice of the silver impregnated Acticoat dressing (Smith & Nephew, UK) for
      burns is well documented due to its recognised sustained bactericidal activity,
      reduction of inflammation and ability to promote healing. Its use in the burnt
      hand, however, is a compromise between adequate dressing cover of this injury and
      the ability to splint and perform hand therapy on the injured limb. Trying to
      wrap individual fingers, maintaining web spaces and keep a relatively light
      dressing for the hand therapists is often difficult and time consuming. We
      introduce a simple, effective method of creating a custom made Acticoat glove
      which provides a thin, light dressing covering the hands allowing full
      mobilisation of the wrist and finger joints.

PMID- 16621301
TI  - Nosocomial infections in a Brazilian Burn Unit.
AB  - In 1-year prospective study, bacterial and fungal infections presenting in burned
      patients were registered. Two-hundred and seventy-eight patients were included.
      The median total body surface area burned was 14% (range 1-100%). The median
      length of hospital stay was 12 days (range 1-86 days). Eighty-six patients had in
      all 148 infections. Seventy-two bloodstream infections (BSI) occurred in 57
      patients; most common microorganisms were coagulase-negative staphylococci and
      methicillin-sensitive Staphylococcus aureus. Forty-nine (17.6%) patients had burn
      wound infections and 18 (6.5%) had pneumonia. Antibiotics were given to only 30%
      of the burn patients. Overall mortality rate was 5.0% (14/278). The database can
      be used to evaluate the effects of changes in burn treatment, staffing and design
      of burn units, and antimicrobial resistance development in relation to antibiotic
      usage.

PMID- 16621302
TI  - Childhood burns in Israel: a 7-year epidemiological review.
AB  - INTRODUCTION: Understanding the etiology of severe burns injuries and identifying
      high risk groups are essential for allotting resources for prevention and
      treatment. The objective of this study was to develop a profile of severe
      childhood burns in Israel. METHODS: A retrospective study of children (ages 0-14)
      hospitalized with a burn, between 1998 and 2004. Data from all five burn units in
      Israel was retrieved from the National Trauma Registry. RESULTS: Two thousand
      seven hundred and five children were hospitalized with burns (51% of all burn
      admissions). Infants (ages 0-1) had the highest prevalence (45%). Scalds caused
      68% of burns. Burn extent in 83% of the patients was less than 20% TBSA, 3%
      suffered 40%TBSA burns. Surgical intervention increased from 6% in 1998 to 21% in
      2002. Non-Jewish children sustained proportionally more burn injuries (48%).
      Among Jewish children an increase in burn injuries was noted on Thursdays and
      Fridays. CONCLUSION: Infants, boys and non-Jewish children were found to be at
      greatest risk for a burn injury, while older children were at higher risk for
      severe burns. Prevention programs should target these high risk groups, with an
      emphasis on the unique characteristics of each group. Policy makers should
      reassess the benefits of a pediatric burn unit in Israel. The increase in rates
      of surgical intervention should be further investigated.

PMID- 16621303
TI  - Non-existence of toxic shock syndrome in Dutch Burns Centres.

PMID- 16621304
TI  - Two cases of total arm-thorax synechia after severe burn.

PMID- 16621305
TI  - Effects of different preservation solutions on skin graft epidermal cell
      viability and graft performance in a rat model.
AB  - This study sought to evaluate the viable epidermal cell count of skin stored at 4
      degrees C in different media, and to determine the longest time that grafts could
      be stored and still be used for clinical application of skin grafts. Harvested
      rat skin grafts were divided into four groups: saline (group 1), Roswell Park
      Memorial Institute-1,640 solution (RPMI) (group 2), University of Wisconsin
      solution (UW) (group 3), and Histidine-tryptophan-ketoglutarate solution (HTK)
      (group 4). After the designated storage time (7, 14, 21, 28, or 35 days), grafts
      were divided into two parts. Skin grafts (3 cm x 3 cm) were then autotransplanted
      onto full-thickness circular wound beds. Percentages of viable keratinocytes
      (PVK) declined significantly for skin grafts stored in UW, HTK, and saline
      solutions (Kruskal-Wallis, P<0.05), while there was an insignificant decline in
      the PVK of skin grafts stored in RPMI until the 28th day of storage (Kruskal
      Wallis, P>0.05). Compared with UW, HTK, and saline, grafts stored in RPMI had
      significantly higher percentages of PCNA at the 14th and 21st days of storage
      (Mann-Whitney U-test, P<0.05). Grafts stored in RPMI had significantly lower
      apoptosis rates than did grafts stored in UW or HTK (P<0.05). Based on these
      results, we conclude that RPMI-1640 provides a better environment for skin grafts
      by increased quality and survival time of skin grafts, as assessed by both
      microscopic and macroscopic investigations.

PMID- 16621306
TI  - Use of cross-leg latissimus dorsi free flap for repair of extensive lower leg
      electrical injury in a child.

PMID- 16621307
TI  - The use of cultured epithelial autograft in the treatment of major burn injuries:
      a critical review of the literature.
AB  - INTRODUCTION: The need to achieve rapid wound closure in patients with massive
      burns and limited skin donor sites led to the investigation of in vitro cellular
      expansion of keratinocytes. The use of cultured epithelial autografts (CEA) was
      first reported in the treatment of major burns in 1981. Since that time, support
      for the use of CEA has varied, ranging from 'a useful agent' to having 'no
      demonstrable effect on the outcome of extensively burned patients'. METHODS: This
      critical review of the literature examines issues associated with the use of CEA
      and the introduction of the technology into clinical practice. The factors
      potentially limiting the use of cultured CEA are the time necessary to culture
      CEA sheets, the reliability of 'take', vulnerability of grafts on the newly
      healed surface, long-term durability and the cost implications of such treatment.
      The available literature was located and critically evaluated using the
      Australian National Health and Medical Research Council Guidelines. FINDINGS: In
      the identified literature, the level of evidence to support the use of CEA in
      major burn injures is limited and often restricted to case studies and case
      series with no Level 1 evidence currently available. CONCLUSION: The main
      question arising 'Does CEA have a role in the treatment of major burns?' has
      proven difficult to answer due to the wide variation in both the quality of study
      design and the findings. At best, the literature review has highlighted areas of
      concern that have hindered the successful use of CEA. Our review critically
      evaluates the use of CEA and explores the advances in techniques towards
      attempting to improve reliable clinical implementation of CEA. The need for
      higher level research into the use of CEA is emphasised by this review.

PMID- 16621308
TI  - Self-inflicted burns, outcome and cost.
AB  - INTRODUCTION: Self-inflicted burns represent a small number of total admissions
      to a burns unit, yet they constitute a major workload. METHODS: A retrospective
      analysis of self-inflicted burns admitted between 1998 and 2002. RESULTS: One
      thousand six hundred and fifty six patients were admitted with acute burn
      injuries, of these 56 were self-inflicted. 24 patients had a previous history of
      self-harming and 22 were unemployed. History of a psychiatric illness was found
      in 46 patients. Flames caused 46 out of 56 injuries. Mean total body surface area
      (TBSA) was 27%. Approximately 39% needed admission to intensive care unit (ICU).
      The mortality rate was 25%. On discharge, 29% of the patients re-self harmed.
      CONCLUSION: Self-inflicted burns have a poorer outcome. Improving the psychiatric
      and social support can reduce the incidence of self-harming behaviour, its
      repetitiveness and subsequently the cost of burn care.

PMID- 16621309
TI  - Language barriers and paediatric burns: does education make a difference?
AB  - A focused first aid education campaign was conducted in Sydney in 1996 for
      parents of children from Non-English speaking backgrounds (NESB) to improve their
      knowledge of correct burns first aid treatment (BFAT). This study sought to
      determine the correlation, if any, between the reported beneficial results of
      this education campaign and the subsequent severity of burns in children. A
      retrospective review of all patients admitted to the state Burns Unit at The
      Children's Hospital at Westmead (CHW) over a 7-year period from January 1995 to
      December 2001 was performed. Number of patients, language spoken at home
      (English, Chinese, Arabic, Vietnamese or Other) and the rate of burns requiring
      skin grafting was assessed. A total of 1,283 patients were admitted over 7 years.
      Skin grafting was required in 544 (42%). NESB children required grafting in up to
      88% of cases prior to the first aid education campaign, reducing to a minimum of
      37% at 1 year and 65% at 5 years following the campaign. This compared to 40 and
      36%, respectively, for English speaking children. While the initial decrease in
      grafting requirements may reflect an effective education campaign, the subsequent
      rise suggests the need for reinforcement.

PMID- 16621310
TI  - Haemophilus Influenzae contributes to morbidity but not mortality in severely
      burned patients.
AB  - Due to a successful Haemophilus Influenzae (HIF) vaccination program, this
      pathogen is no longer a major contributor to childhood morbidity and mortality.
      The effect on adult acquisition of HIF is unknown. The purpose of this study was
      to determine HIF infection frequency in severely burned patients. In a 62-month
      period, there were 1486 admissions. Twenty-four of 1,486 (1.6%) burn patients had
      HIF pneumonia: 16 (1%) within 72 h after injury; 8 (0.5%) patients developed it
      after the seventh day of hospitalization; 74 of 1,486 (5.0%) burn patients had
      pneumonia due to other organisms. There was no statistically significant
      difference between patients with HIF pneumonia and those with other pathogens
      with respect to age, race, sex, percent total body surface area (TBSA),
      inhalation injury, ventilator days, intensive care days, sepsis, or mortality.
      Nineteen percent of patients with HIF were<14 years of age compared to 12% in the
      other pneumonia group, p<0.01. HIF contributed to both an early and late
      pneumonia in burn patients. The organism responded to treatment and did not
      affect mortality.

PMID- 16621311
TI  - Hand burns sustained whilst refuelling car with LPG (liquefied petroleum gas).

PMID- 16621312
TI  - Scalded and swollen-beware the underlying compartment syndrome.

PMID- 16621313
TI  - Localization of antimicrobial peptides in normal and burned skin.
AB  - Severe burn causes immunosuppression, and the eschar remains a perfect culture
      medium for microbial growth. The resulting sepsis is a common complication of
      burns with a high mortality. The skin produces a number of molecules including
      antimicrobial peptides (AMPs) that act in the first line of host defense.
      Previous studies from our laboratory suggested decreased expression of human beta
      defensin-2 (HBD-2) in burned wounds. Here, we have expanded our work by
      identifying HBD-1, HBD-2, HBD-3 and human neutrophil peptide (HNP) in normal and
      burn skin samples using fluorescence deconvolution microscopy. In normal skin,
      HBD-1 was localized to the perinuclear region of keratinocytes, while HBD-2 was
      seen primarily in the stratum basale of the epidermis. HBD-3 was found in
      dendritic cells of the stratum spinosum. HNP was distributed in a somewhat random
      pattern in the papillary dermis. In burned skin, in which the epidermis had been
      destroyed or disrupted, the presence of HBD-1 was localized to dermal glandular
      structures and hair shafts. HBD-2 was found in both the upper portions of the
      remaining keratin layers, and localized to lower, f-actin containing, acini-like
      structures, a pattern also evident with HBD-3. We conclude that although the
      upper layers of skin are destroyed and disrupted by burn, cells in the lower
      portions of the skin demonstrate an ability to synthesize most of the AMPs,
      thereby maintaining some barrier against infection. The results of these studies
      further contribute to an understanding of the role of AMPs in the pathophysiology
      of cutaneous burn and the possibility of using these sites for upregulation of
      AMP synthesis in the prevention of burn sepsis.

PMID- 16621314
TI  - Theoretical evaluation of burns to the human respiratory tract due to inhalation
      of hot gas in the early stage of fires.
AB  - A transient two-dimensional mathematical model for heat and water vapor transport
      across the respiratory tract of human body was established and applied to predict
      the thermal impact of inhaled hot gas to the nasal tissues during the early stage
      of fires. Influences of individual's physiological status and environment
      variables were comprehensively investigated through numerical calculations. Burn
      evaluation was performed using the classical Henriques model to predict the time
      for thermal injury to occur. It was shown that decreasing the air velocity and
      increasing the respiratory rate is helpful to minimize the burn over the
      respiratory tract. The effect of relative humidity of surrounding dry hot air
      could be ignored in predicting burns for short duration exposures. Due to
      evaporation cooling on the mucousal membrane, the burn often occurs at certain
      positions underneath the skin of the tract near the inlet of the respiratory
      tract. Most of the tissues near the surface suffer injury immediately after
      exposure to fire, while in the deeper tissues, serious damage occurs after a
      relatively longer time period. The method presented in this paper may suggest a
      valuable approach to theoretically evaluate the injury of hot air to the human
      respiratory tract under various fire situations.

PMID- 16621315
TI  - A new method in the treatment of postburn scar contractures: double opposing V-Y
      Z plasty.
AB  - PURPOSE: Postburn scar contractures are fairly often seen in many parts of the
      body, and are still a considerable problem for reconstructive surgeons. Although
      the mild to moderate contractures can easily be managed by numerous surgical
      methods, serious contractures usually require more comprehensive surgical
      solutions including multiple Z plasties and rhomboid flaps, each of which have
      disadvantages. We used a new method called "double opposing V-Y-Z plasty" in this
      study. This technique is a combination of V-Y plasty with Z plasty in double
      opposing fashion, both ensuring primary donor site closure. MATERIALS AND
      METHODS: The technique was applied to 21 postburn scar contractures in 14
      patients (9 males and 5 females). The localization most often seen was in the
      hand. RESULTS: The mean follow-up time was 7.6 months. All flaps healed
      uneventfully. An adequate lengthening and functional recovery were achieved in
      all cases. The donor site scars were acceptable in all cases. None of the
      patients developed contracture recurrence in our series. CONCLUSIONS: Double
      opposing V-Y-Z plasty, as a good alternative to multiple Z plasties and multiple
      rhomboid flaps, is a very useful technique to insure more lengthening and to
      prevent recurrence in the treatment of serious postburn scar contractures.

PMID- 16621316
TI  - An experimental study on the repair of full skin loss of nude mice with composite
      graft of epidermal stem cells.
AB  - This study is to constitute a composite skin substitute with epidermal stem cells
      (ESCs) and fibroblasts on collagen sponge. ESCs were selected by rapid attachment
      to collagen IV for 10 min. Collagen was extracted from rat's tail. The matrix
      lattice was fabricated by freeze-dryer and cross-linked with glutaraldehyde.
      Fibroblasts were inoculated on collagen sponge and cultured for 1 week prior to
      inoculation of ESCs. Having cultured for 2 weeks in submerged culture, the
      bioengineered tissue was raised to the air-liquid interface and cultured for 2
      weeks. The artificial skin was then grafted onto full skin loss wounds of nude
      mice. Collagen sponge membrane lacking cell inoculation and an artificial skin
      with epidermal cells (ECs) and fibroblasts were used as controls. The wounds were
      observed daily. Tissue samples were harvested and examined by means of histology,
      immunohistochemistry and electron microscopy. The wounds in the test group healed
      at a significantly faster rate than controls, with good skin appearance and
      minimal scar formation. The control group showed delayed wound healing and
      intensive wound contraction as compared to the test group. Thus the skin
      substitute with ESCs seemed to be a good equivalent.

PMID- 16621317
TI  - Injury-related fear-avoidance, neuroticism and burn-specific health.
AB  - Dysfunctional beliefs such as fear-avoidance (i.e. fear of re-injury) and
      personality traits such as neuroticism are risk factors for poor health. However,
      there is little information regarding associations with poor perceived health
      after severe burn and what level of fear-avoidance is associated with poor
      health. In this study, we investigated fear-avoidance and neuroticism regarding
      their associations with post-burn health. Participants were 86 recovered burn
      patients and data were collected by a postal survey. Post-burn health was
      assessed with the nine subscales of the Burn Specific Health Scale-Brief (BSHS
      B). In logistic regressions, fear-avoidance was related to poorer health in six
      subscales assessing both physical and psychosocial problems. Neuroticism was
      associated with poorer health in three subscales assessing mainly psychosocial
      problems. Chi-square analyses showed that participants with a moderate or high
      level of fear-avoidance >or=1.0 (out of 4) were more likely to describe their
      health as poor and had a longer sick leave than those with a fear-avoidance level
      of <1.0. In summary, fear-avoidance was associated with poorer health even at
      moderate levels and was associated with several aspects of post-burn health.

PMID- 16621318
TI  - Scalding in Turkish children: comparison of burns caused by hot water and hot
      milk.
AB  - INTRODUCTION: Our aim in this study was to compare the clinical differences and
      etiologic risk factors for hot water and hot milk scald burns in Turkish
      children. METHODS: The retrospective study examined the cases of 140 children
      aged 0.1-7 years who had scald burns treated in three burn units of a Turkish
      hospital network between March 2000 and December 2004. The patients were
      categorized in two groups: hot water burns or hot milk burns. RESULTS: Ninety
      five (67.9%) patients had hot water burns and 45 (47.1%) had hot milk burns. The
      proportion of patients with hot milk burns who lived in rural areas was
      significantly higher than the corresponding proportion for the hot water cases
      (75.6% versus 52.6%, respectively; p<0.01). In 20 (44%) of the hot milk cases,
      the burn was caused by milk being boiled in large pots outdoors for cheese
      production. The other 25 hot milk cases were caused by milk being boiled in the
      kitchen. The mean (+/-S.D.) percentage total body surface area burned in the hot
      milk cases was higher than that in the hot water cases (33.6+/-2.24% versus
      21.42+/-1.43%, respectively; p<0.001), and the corresponding mean percentages of
      TBSA with full-thickness burns were 9.2+/-2.52% versus 3.13+/-0.83%,
      respectively; (p=0.083). The mean percentages of TBSA with second-degree burns
      showed the same trend (29.0+/-12.39% versus 18.8+/-1.47%, respectively; p<0.001)
      higher percentage of the children with hot milk burns required antibiotics (78%
      versus 52.8%, respectively; p<0.006). Seven (7.4%) of the hot water burn patients
      and 15 (33.3%) of the hot milk burn patients died during the study period
      (p=0.025; overall mortality rate 15.7%). CONCLUSION: Children scalded with hot
      milk tend to have more extensive burns, and thus have higher mortality, than
      those scalded with hot water. To create effective programs for preventing scald
      injuries in Turkey and elsewhere, it is essential to consider ethnic and cultural
      issues based on these characteristics. Simple precautions should be explained and
      methods of using liquids such as hot milk should be researched in different
      geographic locations in order to formulate good prevention strategies.

PMID- 16621319
TI  - Outbreak of epidemic methicillin-resistant Staphylococcus aureus in a regional
      burns unit: management and implications.
AB  - Colonization of burn patients with methicillin-resistant Staphylococcus aureus
      (MRSA) is not uncommon, however an outbreak that necessitates closure of a burns
      unit is relatively rare. The objective of this study was to present the
      experience of a regional adult burns unit where an outbreak of epidemic MRSA-15
      (EMRSA-15) took place. During the studied period, 176 patients were admitted to
      the unit, 52 with burns, 48 for elective plastic surgery procedures while the
      remainder belonged to other specialties. Patients admitted under burns and
      plastic surgery were investigated together with 46 staff members to control the
      outbreak. MRSA was isolated in 18 patients out of which 12 had EMRSA-15. Among
      the staff members, MRSA was isolated in nine of which five had EMRSA-15. The
      burns unit was closed to all admissions to terminate this outbreak. The MRSA
      positive staff members were sent on "special leave" and underwent treatment with
      nasal mupirocin and triclosan body wash. All staff members were able to return to
      work after one week's treatment. The burns unit underwent re-furbishment and
      decontamination while it was closed. In conclusion, the study shows that an
      outbreak of EMRSA was controlled successfully, however, it highlights the
      implications of such an event for a regional burn service with regard to staff,
      patients and guidelines for management.

PMID- 16621320
TI  - A recombinant anti-ICAM-1 Fab fragment is as effective as the complete IgG
      antibody in treatment of burns in rabbits.
AB  - The purpose of this study was to examine the efficiency of an Anti-ICAM-1-Fab
      fragment in the treatment of burns. Blocking ICAM-1 using murine IgG with the
      purpose to prevent further damage to the zone of stasis has proven its
      effectiveness in animal models as well as in humans. The use of murine Antibodies
      has some disadvantages including allergic reactions and complement activation.
      For the first time we examined an industry produced Fab-fragment blocking ICAM-1
      and compared it to the corresponding IgG antibody. We showed in a standardised
      rabbit burn model that an Fab-fragment is capable of blocking ICAM-1 and
      therefore improving the reaction of the skin to trauma in the zone of stasis.

PMID- 16621321
TI  - A polyurethane dressing is beneficial for split-thickness skin-graft donor wound
      healing.
AB  - Few comparative studies have been performed on the various wound-dressing
      materials or methods proposed for use. To clarify the efficacy of wound dressing,
      35 patients (17 females, aged 44.8+/-26.86 years and 18 males, aged 35.4+/-29.70)
      were subjected to a prospective study comparing a polyurethane dressing and a
      hydrogel dressing for split-thickness skin donors from the lateral thighs. We
      examined their clinical usefulness such as accelerated healing time, frequency of
      changing the dressing, degree of pain, or amount of exudates, and performed
      moisture meter analysis at 1 month and 1 year after re-epithelialization, which
      reflects the quality of the stratum corneum and subsequent scarring. The
      polyurethane dressing was superior to hydrogel in the wound healing time, amount
      of exudates, and frequency of dressing changes: the hydrogel was better for
      regulating the degree of pain. There was a positive correlation between
      transepidermal water loss and the effective contact coefficient, which indicates
      skin barrier function and affected by skin surface electrolytes and reflects
      water content, in moisture meter analysis (r(2)=0.32, p<0.01). Transepidermal
      water loss returned to the control level at 1 year after healing with both
      dressings. The effective contact coefficient of the polyurethane wound was
      significantly lower than that of hydrogel at 1 month (p<0.01), while both
      dressing wounds demonstrated significantly higher values at both 1 month and 1
      year compared to the control (p<0.01). The polyurethane dressing is therefore
      superior both clinically and in moisture meter analysis.

PMID- 16621322
TI  - Melatonin levels in drug-free patients with major depression from the southern
      hemisphere.
AB  - The secretion of melatonin has been shown as abnormal in some depressed patients,
      but most such studies were conducted in the northern hemisphere and with severely
      depressed inpatients. The aim of this study was to evaluate melatonin excretion
      profiles in major depressive outpatients from Sao Paulo, Brazil, individually
      matched to well-screened healthy volunteers to examine whether melatonin
      abnormalities are also present in patients from the southern hemisphere, and in
      less severely ill patients. We analyzed 32 drug-free, depressed outpatients and
      32 psychiatrically healthy volunteers matched for age and gender. We also
      examined a set of 15 drug-free depressed outpatients and 15 healthy volunteers
      that were matched not only for age and gender, but also for body mass index and
      season, all factors known to influence melatonin excretion in humans. All
      patients fulfilled DSM-IV criteria for major depression. We evaluated major
      urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), produced over 24
      h and divided into four periods (06:00-12:00, 12:00-08:00, 18:00-24:00 and 24:00
      06:00 h). aMT6s measurements during the 24 and 6 h intervals were similar in the
      32 depressed patients and 32 healthy volunteers matched for age and gender;
      further matching for body mass index and season did not alter the results. Our
      study supports others in which depressed patients were found to have similar
      melatonin levels than healthy volunteers. Melatonin excretion has been considered
      a physiological index for noradrenergic function, which in some studies were
      found to be altered than depressed patients. It is conceivable that the
      alteration of nocturnal melatonin in depressed patients occurs only in more
      severe depression.

PMID- 16621323
TI  - Corticosterone response to acute stress in a mouse model of Fragile X syndrome.
AB  - Fragile X syndrome (FXS), the most common form of inherited mental retardation,
      results from the silencing of the Fmr1 gene that encodes the Fragile X mental
      retardation protein (FMRP). Because (1) mRNA for the glucocorticoid receptor is
      bound by FMRP and (2) the response to acute stress is elevated in children with
      FXS, we examined whether this heightened response is characteristic of a mouse
      model of FXS. Fmr1 knockout (KO) and wildtype (WT) control mice were exposed to
      30 min of acute restraint; serum corticosterone levels were assayed from
      unstressed animals and those examined either immediately following stress or
      after a 15 or 60 min recovery period. Under unstressed conditions, KOs and WTs
      did not differ in serum corticosterone, although both genotype and sex affected
      corticosterone levels observed following exposure to acute stress. Similar to FXS
      patients, serum glucocorticoid levels of KO mice exhibited a protracted return to
      baseline following acute stress. This suggests that the stress response is
      misregulated in Fmr1 KO mice as in FXS patients and provides the first evidence
      for a link between a particular FMRP-binding mRNA and a functional phenotype of
      FXS (impaired glucocorticoid negative feedback).

PMID- 16621324
TI  - Altered glucocorticoid receptor signaling cascade in lymphocytes of bipolar
      disorder patients.
AB  - Bipolar disorder (BD) is characterized by hypothalamic pituitary adrenal (HPA)
      axis hyperactivity, glucocorticoid insensitivity and alterations in serotonin and
      inflammatory mediators. The glucocorticoid receptor (GR), activator protein-1 (AP
      1), nuclear factor-kappa B (NF-kappaB) and c-jun N-terminal kinase (JNK) regulate
      the above mentioned processes; we therefore assessed their role in BD. Fifteen
      bipolar depressed patients under multiple anti-depressant therapy, 15 bipolar
      euthymics under lithium monotherapy and 25 matched controls were studied. Whole
      cell and nuclear extracts from lymphocytes were immunoblotted for GR, c-fos, JNK
      and NF-kappaB and nuclear aliquots were submitted to electrophoretic mobility
      shift assay for GR, AP-1 and NF-kappaB. Associations with the anti-depressant
      therapy and the state of the disease were also sought. Results, expressed as
      percentage of pooled protein standard sample intergraded optical density (IOD)
      (mean +/- SD), revealed: (a) depressed patients had significantly higher GR
      levels than controls in whole cell (82.63 +/- 6.18 versus 76.27 +/- 4.21%, P <
      0.01) and nuclear extracts (86.66 +/- 3.81 versus 81.72 +/- 2.71%, P < 0.001) but
      lower GR-DNA binding (68.75 +/- 7.91 versus 81.84 +/- 4.25%, P < 0.05). Euthymics
      had normalized whole cell GR content (73.64 +/- 5.95%) and GR-DNA binding
      activity (76.82 +/- 7.29%) but higher nuclear GR content (86.89+/-3.96%, P<0.01)
      than controls; (b) nuclear c-fos content and AP-1-DNA-binding were significantly
      lower in depressed patients than controls (80.49 +/- 2.03 versus 84.82 +/- 3.48%,
      P < 0.05 and 78.46 +/- 4.17 versus 84.80 +/- 5.79%, P < 0.05, respectively).
      Euthymics however, showed similar nuclear c-fos and AP-1-DNA-binding to controls
      (85.48 +/- 2.71 and 87.78 +/- 3.54%, respectively) but lower whole cell c-fos
      than in controls (81.18 +/- 3.87 versus 87.01 +/- 4.22%, P < 0.001); (c)
      depressed patients had significantly lower whole cell and nuclear JNK than
      controls (67.01 +/- 4.29 versus 72.00 +/- 3.68%, P < 0.05 and 80.10 +/- 2.53
      versus 86.96 +/- 2.49%, P < 0.001) whereas euthymics showed lower nuclear JNK
      (83.27 +/- 1.93%, P < 0.01); (d) whole cell NF-kB was higher in the depressed
      patients than in controls (67.30 +/- 5.00 versus 63.63 +/- 3.3%, P < 0.05).
      Concluding, intracellular signaling of GR, AP-1 and JNK are altered in BD and may
      underly disease aetiopathogenesis and/or reflect the effect of the anti
      depressants.

PMID- 16621325
TI  - The effects of growth hormone (GH) deficiency and GH replacement on cognitive
      performance in adults: a meta-analysis of the current literature.
AB  - OBJECTIVE: There is growing evidence in the neuropsychological literature that
      growth hormone (GH) deficiency is associated with cognitive impairment. There is
      also evidence that this impairment may be ameliorated with GH replacement
      therapy. The current study assessed the nature and severity of cognitive
      impairment associated with growth hormone deficiency, as well as effect of GH
      replacement on cognitive function by conducting a meta-analysis of the published
      literature to date. METHOD: Thirteen studies met the inclusion criteria and these
      included: five cross-sectional studies investigating GH deficiency; and, eight
      (eight prospective, two of which also included cross-sectional comparisons)
      investigating GH replacement. Effect sizes (Cohen's d) falling into six cognitive
      domains were computed (separately for GH deficiency and GH replacement). RESULTS:
      For GH deficiency, each of the cognitive domains assessed (besides language)
      showed moderate to large impairments when compared to matched controls (Effect
      sizes -0.46 to -1.46). For GH replacement, even though treated patients still
      performed moderately to largely below that of controls, when compared to their
      own baselines (as in prospective analyses), moderate improvements were found in
      cognitive performance, particularly attention and memory. CONCLUSION: This meta
      analysis clearly demonstrates the link between GH and cognitive performance,
      where poor performance can be ameliorated with GH treatment.

PMID- 16621327
TI  - Sleep-dependent surges in growth hormone do not contribute to sleep-dependent
      memory consolidation.
AB  - In the search for the mechanisms that mediate the effects of sleep on the
      consolidation of memories, growth hormone (GH) recently became of interest,
      because in humans it is released mainly during slow-wave sleep (SWS), a period of
      enhanced declarative memory consolidation. In addition, recent studies showed
      that GH is involved in proper memory function in GH deficient and elderly humans
      and this effect has been linked to regulatory influences of GH on hippocampal
      NMDA receptors. Here, we blocked GH secretion by intravenous infusion of
      somatostatin in healthy young subjects during the first 3 h of sleep, which
      contain mainly SWS. Declarative and procedural memory consolidation was tested
      across this period, using a word pair association task and a mirror tracing task,
      respectively. Although GH was effectively suppressed, memory performance as well
      as sleep were entirely unaffected by this suppression. Whereas GH may in the long
      run generally support brain systems required for maintaining proper memory
      function, our data exclude a necessary contribution of the nocturnal surge in
      pituitary GH secretion to the acute processing and formation of specific memories
      during sleep.

PMID- 16621326
TI  - The four-dimensional stress test: psychological, sympathetic-adrenal-medullary,
      parasympathetic and hypothalamic-pituitary-adrenal responses following inhalation
      of 35% CO2.
AB  - BACKGROUND: Hypercapnia is a threat to homeostasis and results in neuroendocrine,
      autonomic and anxiogenic responses. The inhalation of carbon dioxide (CO2) may,
      therefore, provide a good paradigm for exploring the pathways by which stress can
      lead to increased susceptibility to ill-health through physiological and
      psychological stress reactivity. The current study was designed, therefore, to
      assess the psychological and physiological responses to the inhalation of CO2.
      METHODS: Healthy participants (N = 24) inhaled a single vital capacity breath of
      a mixture of CO2 (35%) and oxygen (65%). Blood pressure and heart rate were
      recorded for 5 min before and after the test and blood and saliva samples were
      taken immediately before and 2, 10, 20 and 30 min post-inhalation for the
      measurement of noradrenaline, salivary and serum cortisol and salivary alpha
      amylase. In addition, psychosomatic symptoms were recorded immediately before and
      after the test. The same protocol was repeated 4-6 weeks later at the same time
      of day. RESULTS: A single inhalation of CO2 increased blood pressure,
      noradrenaline, salivary alpha amylase and psychosomatic symptoms, but decreased
      heart rate at both testing sessions. Analyses of salivary cortisol data revealed
      that 70% of the sample could be reliably classified as either responders (i.e.
      demonstrated a post-CO2 cortisol increase) or non-responders (i.e. responded with
      a decrease or no change in cortisol following CO2) at both test sessions.
      Responders also perceived the test to be more aversive than non-responders.
      CONCLUSIONS: Inhalation of 35% CO2 reliably stimulated the key mechanisms
      involved in the human stress response. The inter-individual differences in the
      reactivity of the hypothalamic-pituitary-adrenal axis were also related to
      differences in the perception of the test.

PMID- 16621328
TI  - Relationship status and testosterone in North American heterosexual and non
      heterosexual men and women: cross-sectional and longitudinal data.
AB  - Previous research has found that single heterosexual (Het) men have higher
      salivary testosterone (T) concentrations than partnered Het men. Here, we used
      both longitudinal and cross-sectional analyses to examine a more diverse
      population (n = 258) that included Het and non-heterosexual (Non-Het) women and
      men. Results showed that, for Het men (but not Het women) and Non-Het women (but
      not Non-Het men), baseline T was significantly lower in partnered than
      unpartnered individuals. Longitudinal analyses indicated that changes in
      partnered status were not associated with changes in testosterone concentrations;
      instead, women and men with lower T at baseline were significantly more likely to
      be partnered at follow-up. These findings thus suggest that partnered status is
      associated with stable, trait-level T values, rather than current state.
      Furthermore, the observed effect is limited to individuals (male or female) who
      are oriented toward female partners. The results are discussed in terms of
      evolutionary trade-offs between single and multiple partners, and the possibility
      of female choice and/or disinterest.

PMID- 16621329
TI  - Breast biopsy and race/ethnicity among women without breast cancer.
AB  - BACKGROUND: Breast biopsy is essential for definitive breast cancer diagnosis,
      but may also play a role in determining eligibility for breast cancer preventive
      measures or clinical trials. In addition, the prevalence of a history of negative
      breast biopsy can be viewed as an indicator of the adequacy or intensity of
      health care in a given population. We therefore analyzed the association of a
      history of breast biopsy with race/ethnicity and other factors in a cohort of
      women without a cancer diagnosis who completed a risk assessment form for
      participation in the Study of Tamoxifen and Raloxifene (STAR) and a
      sociodemographic questionnaire. METHODS: Subjects were recruited at our large,
      urban teaching hospital. We developed a logistic regression model with biopsy
      (ever/never) as the outcome and age, race/ethnicity, educational attainment, and
      insurance coverage as the independent variables. RESULTS: Among 805 unaffected
      predominantly minority subjects, white women were more than three times as likely
      as black and Hispanic women (OR=3.3, 95% CI 1.9-5.9), and insured women were
      twice as likely as uninsured women (OR=2.0, 95% CI 1.4-2.9) to have had a biopsy.
      Biopsy results were also associated with race/ethnicity. DISCUSSION: We view
      these observations as hypothesis-generating rather than definitive. If confirmed,
      the associations we observed between negative biopsies and insurance status may
      reflect disparities in the timeliness and effectiveness of follow-up of
      suspicious lesions found via mammography. Our findings may also be relevant to
      the well-known association of breast cancer stage at diagnosis with low income
      and minority race/ethnicity.

PMID- 16621330
TI  - The present values of delayed rewards are approximately additive.
AB  - In two experiments, human subjects were asked to estimate their present values of
      single delayed rewards and their present values of temporal sequences of three
      rewards. Present values were solicited by asking subjects to indicate an amount
      of money v for which they would be indifferent between receiving v at the end of
      the session and receiving the delayed reward(s). A procedure was used for which
      responding the true value of v was the optimal strategy, and the actual payoff
      that each subject received was determined by one randomly selected trial. In
      Experiment 1 (n=29) each delayed reward was 9.90 dollars in cash. In Experiment 2
      (n=19) the delayed rewards were dated 15 dollars gift certificates to a local
      restaurant. In both experiments, the present values of the sequences were
      approximately equal to the sums of the present values of their component rewards.
      The presence of outliers suggests that a few subjects may have valued sequences
      less than the sums of their single rewards. Effects of a preference for uniform
      sequences, if any, were too small to be detected. Discounting of sequences was
      well fit by a parallel hyperbolic discounting equation, consistent with Mazur's
      [Mazur, J.E., 1986. Choice between single and multiple delayed reinforcers. J.
      Exp. Anal. Behav. 46 (1), 67-77] results using multiple reinforcers.

PMID- 16621331
TI  - Evidence that pigeons represent both time and number on a logarithmic scale.
AB  - Pigeons were presented with trials that always began with presentation of a
      houselight that lasted for 1-16s. Red and green side keys were presented
      immediately after the houselight went off. A peck on the red key was reinforced
      if the houselight duration was 8s or shorter, and a peck on the green key was
      reinforced if the houselight duration was 9s or longer. Plots of asymptotic
      performance as a function of houselight duration showed bow-shaped curves with
      higher accuracy at the ends of the scale than in the middle. Training to bisect a
      scale containing houselight durations of 2-32s yielded a performance curve that
      superimposed on the 1-16s curve. Both curves showed two important asymmetries
      around the midpoint: pigeons were more accurate at 9 and 10s than at 7 and 8s but
      were more accurate at 1-4s than at 13-16s. These findings closely resembled those
      found in a similar study of number scale bisection [Roberts, W.A., 2005. How do
      pigeons represent numbers? Studies of number scale bisection. Behav. Process. 69,
      33-43]. Theoretical predictions from associative and confusion models showed a
      good match to the obtained data if it was assumed that time and number scales
      were logarithmic and that generalization or confusion curves were constant but
      not if it was assumed that scales were linear and that generalization or
      confusion curves were scalar.

PMID- 16621332
TI  - "Let There be Light!" pigeon eggs are regularly exposed to light during breeding.
AB  - Light stimulation before hatching initiates the emergence of avian visual
      lateralisation. Since several studies show that birds benefit from being
      lateralised, we can conjecture that their clutch is being exposed to light during
      breeding. We tested this assumption in pigeons with a semi-natural setup where
      the animals were systematically recorded using a movement detection system
      throughout their breeding period. The results show that pigeon pairs perform
      their relieves in a regular way by abandoning their clutch for a mean of about 55
      s at approximately every 43 min. Thus, the developing visual pathways are
      repetitively stimulated by light for cumulatively over 3h before the breeding
      period ends. It becomes apparent that both the duration as well as the
      repetitions of light stimulation play a crucial role in the onset of visual
      asymmetry.

PMID- 16621333
TI  - Mechanisms of same/different concept learning in primates and avians.
AB  - Mechanisms of same/different concept learning by rhesus monkeys, capuchin
      monkeys, and pigeons were studied in terms of how these species learned the task
      (e.g., item-specific learning versus relational learning) and how rapidly they
      learned the abstract concept, as the training set size was doubled. They had
      similar displays, training stimuli, test stimuli, and contingencies. The monkey
      species learned the abstract concept at similar rates and more rapidly than
      pigeons, thus showing a quantitative difference across species. All species
      eventually showed full concept learning (novel-stimulus transfer equivalent to
      baseline: 128-item set size for monkeys; 256-item set for pigeons), thus showing
      a qualitative similarity across species. Issues of stimulus regularity/symmetry,
      generalization from item pairs, and familiarity processing were not considered to
      be major factors in the final performances, converging on the conclusion that
      these species were increasingly controlled by the sample-test relationship (i.e.,
      relational processing) leading to full abstract-concept learning.

PMID- 16621334
TI  - Variation of bar-press duration: where do new responses come from?
AB  - Instrumental learning involves both variation and selection: variation of what
      the animal does, and selection by reward from among the variation. Four
      experiments with rats suggested a rule about how variation is controlled by
      recent events. Experiment 1 used the peak procedure. Measurements of bar-press
      durations showed a sharp increase in mean duration after the time that food was
      sometimes given. The increase was triggered by the omission of expected food. Our
      first explanation of the increase was that it was a frustration effect.
      Experiment 2 tested this explanation with a procedure in which the first response
      of a trial usually produced food, ending the trial. In Experiment 2, unlike
      Experiment 1, omission of expected food did not produce a large increase in bar
      press duration, which cast doubt on the frustration explanation. Experiments 3
      and 4 tested an alternative explanation: a decrease in expectation of reward
      increases variation. Both used two signals associated with different
      probabilities of reward. Bar presses were more variable in duration during the
      signal with the lower probability of reward, supporting this alternative. These
      experiments show how variation can be studied with ordinary equipment and
      responses.

PMID- 16621335
TI  - The sampling distribution of kappa.
AB  - Research on Herrnstein's single-schedule equation contains conflicting findings;
      some laboratories report variations in the k parameter with reinforcer value, and
      others report constancy. The reported variation in k typically occurs across very
      low reinforcer values, and constancy applies across higher values. Here,
      simulations were conducted assuming a wide range of reinforcer values, and the
      parameters of Herrnstein's equation were estimated for simulated responding. In
      the simulations, responses controlled by current reinforcement contingencies were
      added to other responses ('noise'), controlled by the experimental environment
      and by contingencies in effect at other times. Expected reinforcer rates were
      calculated by entering simulated responding into a reinforcement feedback
      function. These were then fitted using Herrnstein's hyperbola, and the sampling
      distributions of the two fitted parameters were studied. Both k and Re were
      underestimated by curve fitting when low-deprivation or reinforcer-quality
      conditions were simulated. Further simulations showed that k and Re were
      increasingly underestimated as the assumed noise level was increased,
      particularly when low-deprivation or reinforcer quality was assumed. It is
      concluded that reported variations in k from single schedules should not be taken
      to indicate that the asymptotic rate of responding depends on reinforcement
      parameters.

PMID- 16621336
TI  - SQAB 2005: complexity and generalizability.

PMID- 16621337
TI  - The relationship between past-year drinking behaviors and nonmedical use of
      prescription drugs: prevalence of co-occurrence in a national sample.
AB  - This study examined the relationship between past-year drinking behaviors and
      nonmedical use of prescription drugs (NMUPD) in a nationally representative
      sample. Prevalence estimates in the United States were derived based on data
      collected from face-to-face interviews using the National Epidemiologic Survey on
      Alcohol and Related Conditions (NESARC) (n=43,093 individuals aged 18 years and
      older). Nonmedical use of prescription opioids, stimulants, tranquilizers, and
      sedatives was more prevalent among individuals with alcohol use disorders (AUDs)
      than those without AUDs. The odds of reporting NMUPD were 18 times higher among
      alcohol dependent participants compared to past-year abstainers (OR=18.2, 95%
      CI=13.9-23.8). Although individuals with AUDs constituted less than 9% of the
      total sample, those with AUDs accounted for more than one in every three
      nonmedical users of prescription drugs. The past-year co-occurrence of AUDs and
      NMUPD was more prevalent among young adults 18-24 years of age than individuals
      25 years and older. More than one in every four young adults aged 18-24 years who
      met the criteria for past-year DSM-IV alcohol dependence also reported past-year
      NMUPD. These findings suggest that the treatment for AUDs should include a
      thorough assessment of NMUPD, especially among young adults.

PMID- 16621338
TI  - A systems approach to care pathways into in-patient alcohol detoxification:
      outcomes from a retrospective study.
AB  - This paper describes the effects of the adoption of a systems approach to alcohol
      service delivery by four previously separate organisations in Manchester, UK that
      commenced in 1997. The study examined a database of 5542 admissions for in
      patient detoxification between 1995 and 2003, which permitted the analysis of
      changes occurring in the composition of the client group after the adoption of
      the new model. Findings suggest that working with the systems approach resulted
      in more effective targeting of people with higher levels of alcohol dependency
      towards in-patient detoxification. Females and people in stable housing also
      benefited from increased access in the new system. Increases in planned
      discharges were observed across all demographic variables, although alcohol
      dependent males without stable accommodation found it more difficult to access in
      patient detoxification after the new model was introduced. We conclude that in
      comparison to a loose network of services a co-ordinated and managed service
      system can improve targeting for in-patient detoxification for most people with
      severe alcohol dependence but may not do so for all who need access.

PMID- 16621339
TI  - Randomized, placebo-controlled trial of sertraline and contingency management for
      the treatment of methamphetamine dependence.
AB  - BACKGROUND: Methamphetamine dependence and associated medical and psychiatric
      concerns are significant public health issues. This project evaluated the
      efficacy of sertraline (50mg bid) and contingency management (CM) for the
      treatment of methamphetamine dependence. METHOD: In this randomized, placebo
      controlled, double-blind trial, participants completed a 2-week non-medication
      baseline and were randomized to one of four conditions for 12 weeks: sertraline
      plus CM (n=61), sertraline-only (n=59), matching placebo plus CM (n=54), or
      matching placebo-only (n=55). All participants attended clinic thrice-weekly for
      data collection, medication dispensing, and relapse prevention groups. Outcomes
      included methamphetamine use (urine drug screening and self-reported days of
      use), retention (length of stay), drug craving (visual analogue scale), and mood
      symptoms (Beck Depression Inventory). RESULTS: No statistically significant main
      or interaction effects for sertraline or CM in reducing methamphetamine use were
      observed using a generalized estimating equation (GEE), although post hoc
      analyses showed the sertraline-only condition had significantly poorer retention
      than other conditions (chi(2) (3)=8.40, p<0.05). Sertraline conditions produced
      significantly more adverse events than placebo conditions. A significantly higher
      proportion of participants in CM conditions achieved three consecutive weeks of
      methamphetamine abstinence than those in non-CM conditions. CONCLUSIONS: These
      data do not demonstrate improved outcomes for sertraline versus placebo for
      treatment of methamphetamine dependence; indeed, they suggest sertraline is
      contraindicated for methamphetamine dependence. Findings provide support for the
      use of contingency management for treatment of methamphetamine dependence.

PMID- 16621340
TI  - BSE infection in bovine PrP transgenic mice leads to hyperphosphorylation of tau
      protein.
AB  - We observed the changes in the central nervous system (CNS) of transgenic mice
      expressing bovine prion protein (Bo-PrP) as a contribution to our knowledge of
      the pathogenesis of bovine spongiform encephalopathy (BSE). The main result was
      the detection of hyperphosphorylated tau. This protein was detected for the first
      time, using immunohistochemical techniques, in the neurons and glial cells of
      mice experimentally infected with BSE. The results highlighted the involvement of
      tau protein in the pathogenesis of BSE and the close link between
      hyperphosphorylated tau deposits and prion protein. Ultrastructural examination
      revealed a novel arrangement of intraneuronal tau deposits not hitherto reported.

PMID- 16621341
TI  - Sequence analysis of the non-structural 3A and 3C protein-coding regions of foot
      and-mouth disease virus serotype Asia1 field isolates from an endemic country.
AB  - A total of 18 foot-and-mouth disease virus (FMDV) serotype Asia1 field isolates
      belonging to two different lineages (including the divergent group) as delineated
      earlier in VP1-based phylogeny were sequenced in the non-structural 3A and 3C
      protein-coding regions. The phylogenetic trees representing the regions coding
      for the non-structural proteins were very similar to that of the structural VP1
      protein-coding region. Phylogenetic comparison at 3C region revealed clustering
      of Asia1 viruses with the isolates of serotypes O, A and C in the previously
      identified clade. Comparison of amino acid sequences identified lineage-specific
      signature residues in both the non-structural proteins. Overall analysis of the
      amino acid substitutions revealed that the 3A coding region was more prone to
      amino acid alterations than 3C region.

PMID- 16621342
TI  - Development of an enzyme-linked immunosorbent assay for the detection of
      antibodies against malignant catarrhal fever viruses in cattle serum.
AB  - Malignant catarrhal fever (MCF) is a sporadic but fatal lymphoproliferative viral
      disease of cattle, deer and other ruminants. The causative agents are highly-cell
      associated herpesviruses of the subfamily gammaherpesvirinae. In this study, an
      ELISA (WC11-ELISA) was developed to detect antibody to malignant catarrhal fever
      virus (MCFV) in cattle serum and compared to the commercially produced
      competitive-inhibition ELISA (CI-ELISA). Crude lysate antigen from alcelaphine
      herpesvirus-1 strain WC11 was bound to 96-well microplates and used to capture
      antibodies to MCFV. Dilutions of test sera were added to wells containing bound
      MCF antigen and control wells containing uninfected cell lysates. A horseradish
      peroxidase-labelled rabbit-anti-bovine IgG conjugate detected antibodies to MCF,
      and the results were expressed as absorbance readings at 450 nm. Samples were
      selected blind from cattle sera which had been sent to the laboratory for
      diagnostic testing for MCFV antibodies and were tested in both the WC11-ELISA and
      the CI-ELISA. Good agreement between the WC11-ELISA and CI-ELISA test (k=0.86,
      n=95) results was found.

PMID- 16621343
TI  - Distribution of RTX toxin genes in strains of [Actinobacillus] rossii and
      [Pasteurella] mairii.
AB  - Strains of [Actinobacillus] rossii, [Pasteurella] mairii and [Pasteurella]
      aerogenes can be isolated from abortion in swine. The RTX toxin Pax has
      previously been found only in those [P.] aerogenes strains isolated from
      abortion. Nothing is known about RTX toxins in field isolates of the other two
      species. To gain insight into the distribution of selected RTX toxin genes and
      their association with abortion, PCR screening for the pax, apxII and apxIII
      operons on 21 [A.] rossii and seven [P.] mairii isolates was done. Since species
      can be phenotypically misidentified, the study was backed up by a phylogenetic
      analysis of all strains based on 16S rRNA, rpoB and infB genes. The pax gene was
      detected in all [P.] mairii but not in [A.] rossii strains. No apx genes were
      found in [P.] mairii but different gene combinations for apx were detected in
      [A.] rossii strains. Most of these strains were positive for apxIII, either alone
      or in combination with apxII. Whereas pax was found to be associated to strains
      from abortion no such indication could be found with apx in [A.] rossii strains.
      Phylogenetically [A.] rossii strains formed a heterogeneous cluster separated
      from Actinobacillus sensu stricto. [P.] mairii strains clustered with [P.]
      aerogenes but forming a separate branch. The fact that [P.] aerogenes, [P.]
      mairii and [A.] rossii can phylogenetically clearly be identified and might
      contain distinct RTX toxin genes allows their proper diagnosis and will further
      help to investigate their role as pathogens.

PMID- 16621344
TI  - Experimental aerosol infection of cattle (Bos taurus) with ovine herpesvirus 2
      using nasal secretions from infected sheep.
AB  - Infection of clinically susceptible ruminants, including domesticated cattle and
      American bison, with ovine herpesvirus 2 (OvHV-2) can result in the fatal
      lymphoproliferative and vasculitis syndrome known as malignant catarrhal fever
      (MCF). A reliable experimental infection model is needed to study the
      pathogenesis of MCF and to develop effective vaccination strategies to control
      the disease. An experimental aerosol infection model using sheep, the natural
      carriers of OvHV-2, has been developed (Taus et al., 2005). Using the protocol
      and OvHV-2 inoculum established in the previous study, eight calves were
      nebulized with four different doses of OvHV-2 in nasal secretions from infected
      sheep. Two control calves were nebulized with nasal secretions from uninfected
      sheep. Infection status of all calves was monitored using competitive inhibition
      ELISA, PCR and clinical parameters. Six of eight nebulized calves became infected
      with OvHV-2. One calf receiving the highest dose of virus developed typical
      clinical, gross and histological changes of MCF. This study showed that nasal
      secretions collected from sheep experiencing OvHV-2 shedding episodes were
      infectious for cattle and capable of inducing MCF. The data also indicate that
      cattle are relatively resistant to disease following infection. The use of more
      susceptible species as experimental animal models, such as bison and selected
      cervid species should be examined.

PMID- 16621345
TI  - Arcobacter, what is known and unknown about a potential foodborne zoonotic agent!
AB  - Since the introduction of the genus Arcobacter in 1991, the association of
      Arcobacter butzleri, Arcobacter cryaerophilus and Arcobacter skirrowii with
      humans and animals has been clearly established. These bacteria have been
      detected world wide in products of animal origin and in healthy animals as well
      as in surface water. A fourth species Arcobacter cibarius was recently discovered
      on chicken carcasses. Although evidence was found for the connection of
      Arcobacter spp. with human and animal illness, Arcobacter spp. can be pathogens,
      opportunistic pathogens and commensals. Their potential as zoonotic foodborne and
      waterborne agents, the routes of transmission and the pathogenic mechanisms of
      these bacteria are largely unknown. Production of toxins or other virulence
      factors has not been demonstrated but adhesive and/or invasive properties were
      apparent. Antibiotic resistance is present in Arcobacter strains to significant
      levels. The tools to genetically access Arcobacter-like transformation of
      strains, construction of mutants are not yet available. Nor have genes (i.e.
      potential virulence factors) been cloned, expressed and characterized in other
      host organisms. Therefore those interested in the microbiology of these organisms
      eagerly await publication of the complete nucleotide sequence of the Arcobacter
      genome. The abundant presence of four Arcobacter species in foods of animal
      origin and the recovery of these bacteria from surface and drinking water suggest
      an important role of these bacteria as foodborne or waterborne agent and possibly
      as zoonotic agent.

PMID- 16621346
TI  - Characterisation of Erysipelothrix rhusiopathiae isolates from pigs associated
      with vaccine breakdowns.
AB  - Swine erysipelas vaccines are routinely used to protect pigs against peracute and
      acute/urticarial forms of Erysipelothrix. Between 1995 and 1998, 34 swine herds
      across four Australian states experienced vaccine failure. Forty-four isolates of
      Erysipelothrix rhusiopathiae of serovars 2, 1a, 1b and 1bx21 were recovered from
      15 of these 34 vaccine breakdown herds. These isolates were characterised by
      restriction fragment length polymorphism (RFLP) analyses using RsaI and AluI on
      whole cell DNA and for the presence of plasmid DNA. Results were compared with
      those of 20 isolates from 16 herds unaffected by vaccine breakdown and 13
      isolates representing 10 reference strains. The majority of breakdown herds
      possessed isolates of serovar 2 (9/15 herds), followed by serovar 1a (5 herds).
      No geographic predominance of a single serovar was evident. The identification of
      10 RsaI profiles from whole cell DNA among the 44 isolates from 15 breakdown
      herds indicated that a single, new clonal lineage of E. rhusiopathiae was not
      responsible for vaccine failure. RsaI RFLP analyses detected a further 14
      distinct profiles among 20 field strains unassociated with vaccine breakdowns,
      and none matched profiles of the 10 serovar reference strains for serovars 1a,
      1b, 2 or 21. This technique is recommended for epidemiological studies of E.
      rhusiopathiae strains.

PMID- 16621347
TI  - 17beta-hydroxy-5alpha-androst-1-en-3-one (1-testosterone) is a potent androgen
      with anabolic properties.
AB  - Since the begining of the year 2005, the use of steroid precursors (prohormones)
      is illegal in the United States; nevertheless, there is still an enormous abuse
      of such substances. One of the most frequently misused steroids, often declared
      to be a prohormone, is 1-testosterone (17beta-hydroxy-5alpha-androst-1-en-3-one,
      1-Testo). In this study, we have characterised molecular mechanisms of its
      action, determined its tissue specific androgenic and anabolic potency and
      investigated potential adverse effects. 1-Testo binds highly selective to the
      androgen receptor (AR) and has a high potency to stimulate AR dependent
      transactivation. In vivo an equimolar dose of 1-Testo has the same potency to
      stimulate the growth of the prostate, the seminal vesicles and the androgen
      sensitive levator ani muscle as the reference compound testosterone propionate
      (TP). Administration of 1-Testo, in contrast to TP, results in a significant
      increase of liver weight. Our results demonstrate that 1-Testo, even without
      being metabolised, is a very potent androgen. It binds selectively to the AR and
      transactivates AR dependent reporter genes. In vivo it has a high androgenic and
      anabolic potency and increases liver weight. In summary 1-Testo can be
      characterised as a typical anabolic steroid. It has to be assumed that
      consumption of this substance is associated with adverse side effects typical for
      this class of compounds. Therefore, a strict control of its ban is essential.

PMID- 16621348
TI  - Comments on "Particle surface characteristics may play an important role in
      phytotoxicity of alumina nanoparticles" by Yang, L., Watts, D.J., Toxicology
      Letters, 2005, 158, 122-132.

PMID- 16621349
TI  - Comparison of the effect of estradiol benzoate plus progesterone and GnRH on the
      follicular wave emergence and subsequent follicular development in CIDR-treated,
      lactating dairy cows with follicular cysts.
AB  - This study examined the effect of estradiol benzoate (EB) plus progesterone (P4)
      as compared with GnRH on follicular wave emergence and follicular development,
      and synchrony of ovulation and pregnancy rates following a second injection of
      GnRH in a controlled internal drug release (CIDR)-based timed AI (TAI) protocol
      in lactating dairy cows with follicular cysts. Lactating dairy cows diagnosed
      with follicular cysts received a CIDR device, with an injection of 2mg EB plus
      50mg P4 (EB+P4 group) or with an injection of 100 microg GnRH (GnRH group) at the
      beginning of the experiment (day 0). Thereafter, all received PGF(2alpha) at the
      time of CIDR removal on day 7, GnRH on day 9, and TAI 16 h later. Follicular wave
      emergence occurred within 7 days in 12/15 EB plus P4-treated and 14/15 GnRH
      treated cows (P>0.05). The interval to wave emergence was longer in the EB+P4
      group (4.8+/-0.4 days) than in the GnRH group (2.0+/-0.2 days). The mean
      diameters of preovulatory follicles and the proportion of cows with preovulatory
      follicles greater than 12 mm on day 9 did not differ between groups (P>0.05). The
      proportion of cows with synchronized ovulations by 40 h after the GnRH injection
      on day 11 and pregnancy rates to TAI did not differ between the EB+P4 (13/15 and
      36.7%) and the GnRH (14/15 and 53.3%) groups, respectively. Results suggest that
      a single treatment with EB plus P4 as compared with GnRH simultaneously with CIDR
      insertion in lactating dairy cows with follicular cysts will result in relatively
      asynchronous emergence of a new follicular wave, but subsequently similar sizes
      of preovulatory follicles and synchronous ovulation, resulting in similar
      pregnancy rates to TAI.

PMID- 16621350
TI  - Morphological and histochemical characterization of the seminiferous epithelial
      and Leydig cells of the turkey.
AB  - Unlike mammals, there is little fundamental information about spermatogenesis in
      birds. This study was undertaken to clarify the morphology, histochemistry, and
      lectin affinity of the seminiferous epithelial cells and Leydig cells in pre
      pubertal (8- to 15-week old) and adult (40- to 44-week old) domestic turkeys. In
      adult turkeys, three types of spermatogonia were defined based on their chromatin
      distribution and nuclear morphology: the dark type A (A(d)); the pale type A
      (A(p)); and the type B. The A(d) is the least numerous and least conspicuous and
      consequently difficult to locate. Based on its spatial distribution and overall
      morphology, type A(d) spermatogonia were postulated to be the spermatogonia stem
      cells in the turkey. Antibodies to c-kit were localized to spermatogonia in the
      pre-pubertal and to a lesser extent in adult males. Peanut agglutinin (PNA) was
      specific for spermatocytes in the pre-pubertal males and spermatogonia and early
      spermatocytes in adult males. Wheat-germ agglutinin (WGA) highlighted Sertoli
      cells in both age groups. Bandeiraea simplicifolia I, soybean agglutinin, and
      winged-pea agglutinin staining were limited to the wall of the seminiferous
      tubule and some extra-tubular cell types. Concanavalin A staining was diffuse and
      not cell-specific and, therefore, could not be used to selectively identify a
      particular cell type. It was concluded that WGA and PNA could aid in identifying
      specific cell types in the seminiferous epithelium of testis from pre-pubertal
      and mature turkeys. Only Leydig cells were alkaline phosphatase reactive in the
      mature turkey testes. The information from this study is being used to adapt
      techniques for the isolation and partial purification developed for mammalian
      spermatogonia to avian spermatogonia and other specific cell types in the testes.

PMID- 16621351
TI  - Surfactant proteins A and D in the genital tract of mares.
AB  - The presence of surface-active material in the lung alveolus has been known for
      several decades as being essential for normal lung function. Surfactant is
      essential for reducing the surface tension at the alveolar air-liquid interface.
      Pulmonary surfactant is composed of 90% lipids and 10% proteins. There are four
      non-serum proteins surfactant protein-A (SP-A), surfactant protein-B (SP-B),
      surfactant protein-C (SP-C) and surfactant protein-D (SP-D) named in chronologic
      order of discovery. Lung SP-A and SP-D belong to a family of collagen-containing
      C-type lectin family called collectins. The host defence and controlling
      inflammatory processes of the lung are the major functions of SP-A and SP-D. SP-A
      and SP-D were originally demonstrated in alveolar type II cells, but recent
      studies have shown extrapulmonary expression of SP-A and SP-D indicating systemic
      roles of these proteins. Present study describes the presence of SP-A and SP-D in
      the mare genital tract, vulva, vagina, ovarium, uterus and tuba uterina using
      immunohistochemistry and Western blotting. The aim of this study was to
      characterize surfactant proteins in terms of: (i) whether surfactant proteins
      were present in the various structures of the mare genital system, (ii) if so,
      identifying and locating the surfactant proteins and finally (iii) determining
      the differences from those previously characterized for the lung. Although beyond
      the scope of this report, it is recognized that there are also some potential
      implications for better defining the reproductive defence mechanisms in mare.
      Therefore, genital system organs and tissues from mares were examined. We were
      able to show that proteins reactive with surfactant-specific antibodies were
      present in the mare genital tract. Thus, surfactant proteins are present not in
      just lamellar bodies associated with lung, but also genital system of mare.

PMID- 16621352
TI  - Infection of bovine oviduct cell cultures with Chlamydophila abortus.
AB  - Bovine infertility is a major cause of loss in the livestock industry. In the
      present study bovine oviduct cell cultures were infected with a Chlamydophila
      abortus strain. A direct evaluation of infection was performed by means of May
      Grunwald-Giemsa and immunocytochemistry for chlamydial LPS, which revealed
      inclusion bodies and vacuolisation. SEM and TEM analysis of infected cells showed
      various degrees of cell damage and conglutination of microvilli. This finding
      suggests that cattle infertility may result from an alteration of oviduct
      environment caused by multiplication of C. abortus. This microorganism, among
      other infectious agents, could be considered a potential causative agent of
      bovine infertility.

PMID- 16621353
TI  - Ovarian follicular dynamics after cauterization of the dominant follicle in
      anestrous ewes.
AB  - An experiment was conducted to ascertain if follicles could reach ovulatory size
      after the largest follicle (dominant) has been removed at different times during
      a progestin treatment in anestrous ewes, and secondly to determine if these new
      follicles could respond to an hCG-induced ovulation and have similar function as
      corpora lutea. Mature crossbred sheep (n=44) in anestrous were treated with an
      intravaginal sponge containing 40 mg of FGA (day 0=sponge insertion) for 9 days.
      Treatments consisted of cauterization of the largest follicle on the experimental
      day 3 (T1), day 6 (T2) and day 9 (T3); day 12 to ascertain the size of the
      largest follicle in control ewes. During laparotomies, the diameters of the
      largest follicle (DF), and those of the second and third largest follicles (SF1
      and SF2, respectively) were determined. On day 12, a second laparotomy was
      performed for those ewes which had their DF cauterized on days 3, 6 and 9, a
      fourth group was left intact and only laparotomized on day 12. At this time, the
      size of the new DF, SF1 and SF2 were determined. Immediately after the laparotomy
      on day 12, all the ewes were treated with 1000 i.u. of hCG to induce ovulation.
      Blood samples were collected daily from day 0 to 50 and samples were analyzed for
      progesterone concentrations. The size of the DF at the time of sponge removal was
      smaller that those observed on day 3 or 6 of sponge suggesting that follicles in
      ewes treated with this progestin regress and a new wave of follicular development
      ensues between day 6 and the time of sponge removal. The size of the DF on day 12
      was also smaller in ewes that have the largest follicle removed at the time of
      sponge removal reflecting that these follicles had a shorter period of growth;
      however, the rate of growth was greater for these follicles than for follicles
      arising after cauterization on day 3 or 6 after sponge insertion. There were no
      differences among treatments, in the number of ewes that formed a corpus luteum
      (CL) in response to hCG. Life span of the corpora lutea did not differ among ewes
      having their DF removed on day 6 or 9 or those that served as controls, however,
      ewes that had their DF removed on day 3 developed longer lived CL in a larger
      proportion of animals. Average progesterone concentration during the life span of
      the induced corpora lutea was greater in control ewes than in any other
      experimental group. These observations allow us to conclude that, (a) the
      follicular dynamics observed in anestrous ewes treated with a progestin
      intravaginal sponge resembles that observed during the normal estrous cycle in
      the ewe; (b) the effects of progesterone on life span of the corpus luteum could
      not be only related to direct effects at the follicle but also involve changes in
      other components of the uterine-ovarian-hypothalamic axis; (c) the mechanisms
      controlling luteal life span seem to be different to those mechanisms controlling
      the function of the induced corpus luteum.

PMID- 16621354
TI  - The postpartum buffalo. II. Acyclicity and anestrus.
AB  - Prolonged postpartum acyclicity (absence of ovarian cyclic activity) and anestrum
      (absence of overt estrous signs) are major sources of economic loss to buffalo
      breeders. Studies on the epidemiology of these two problems are highly
      recommended to achieve successful control. Review of the available literature on
      controlled studies in dairy buffaloes revealed that first ovulation as detected
      by rectal palpation and progesterone analysis occurred between 28-71 and 24-55
      days, respectively, after calving. Postpartum estrus in the same studies occurred
      between 44 and 87 days. Reports concerned with data compiled from breeding
      records of research stations, breeding farms and small holders where estrus is a
      subjective measure, gave much longer periods. Also data from Egypt, India and
      Pakistan indicate that only 34-49% of buffaloes showed estrus during the first 90
      days after calving and 31-42% remained anestrus for more than 150 days. In swamp
      buffaloes both postpartum ovulation and estrus are more delayed than in dairy
      buffaloes. The role of suckling, nutrition, body condition score at calving, milk
      yield, parity, season of calving and other minor factors were discussed. First
      postpartum ovulation is frequently followed by one or more short estrous cycles
      (<18 days). Long anovulatory and anestrous periods due to prolonged inter-luteal
      phase were reported to occur after short cycles. Also long anestrous periods due
      to cessation of cyclic activity (true anestrus) for 3 or more weeks and prolonged
      luteal activity for 28 days or more were described to occur in about 25 and 8-11%
      of the buffaloes, respectively, after the first or second ovulation. These cycle
      irregularities certainly impose difficulties on estrus detection programs in
      postpartum buffaloes. Four main forms of anestrus i.e. true anestrus (inactive
      ovaries and small and medium sized anovulatory follicles), subestrus, prolonged
      luteal activity and ovarian cysts in addition to pregnancy are reviewed in this
      article. Differentiation between true anestrus and subestrus is particularly
      important in buffaloes because of their weak estrous signs. However, the accuracy
      of a single rectal palpation of the ovaries is limited with an overestimation of
      the frequency of true anestrus due to misdiagnosis of the corpus luteum. The
      possible causes are discussed.

PMID- 16621355
TI  - Development and quality of sheep embryos cultured in commercial G1.3/G2.3
      sequential media.
AB  - Present study assesses the developmental ability and quality of ovine IVP embryos
      derived from culture in sequential media G1.3/G2.3. A total of 1474 cumulus
      oocyte complexes were matured in M199 supplemented with EGF and FCS for 24h in 5%
      CO2 in humidified air at 39 degrees C. Oocytes were co-incubated in SOF medium
      with 1 x 10(6) spermatozoa/ml at the same temperature and gas conditions (Day 0
      p.i.). Presumptive zygotes at 20 h p.i. were denuded, washed and placed in
      culture in SOF (control; n=742) or G1.3 media supplemented with 3mg/ml of BSA
      (n=732) under mineral oil in a humidified and controlled atmosphere at 39 degrees
      C. Embryos in the treated group were changed to G2.3 medium on Day 3 of culture.
      A group of blastocysts in each group were frozen by conventional method (SOF,
      n=55; G1.3/G2.3, n=48). In vivo embryos (n=72) were recovered at Day 7 from the
      uterus of progestagen+eCG treated females and they were cultured in defined
      medium (n=38) or frozen (n=34) directly after recovery. Cleavage rate of IVP
      embryos recorded at 48 h p.i. was similar for control and treated embryos (49.8
      versus 47.5%). There were no significant differences in blastocyst development
      from the two groups on Day 6 (26.0 versus 25.6%), 7 (42.1 versus 38.6%) or 8
      (50.8 versus 43.2%). Blastocyst development rates from total oocytes cultured
      were comparable (24.1 versus 21.5%). However, the proportion of hatched
      blastocysts was significantly higher for control embryos (86.6 versus 44.3%,
      P<0.0001). In addition, embryos cultured in SOF had higher re-expansion rates
      post-thawing at 24h (38.2 versus 6.2%), 48 h (36.4 versus 4.1%) and 72 h (34.5
      versus 4.1%) and hatching rate (32.8 versus 2.0%) than embryos cultured in
      sequential media (P<0.0001). In vivo embryos showed higher hatching rate (61.7%)
      than IVP groups (SOF, P<0.01; G1.3/G2.3, P<0.0001) but lower than their fresh
      cultured counterparts (86.8%; P=0.01). In conclusion, G1.3/G2.3 media supported
      high developmental rates of embryos in vitro but the quality of the embryos was
      impaired.

PMID- 16621356
TI  - Elevated arterial stiffness in postmenopausal women with osteoporosis.
AB  - OBJECTIVES: Osteoporosis and increased pulse wave velocity (PWV) are
      cardiovascular risk factors. We investigated the relationship between PWV and
      bone mass in the lumbar spine in postmenopausal women. METHODS: We studied the
      PWV in 95 women; 38 postmenopausal women with normal spinal bone mineral density
      (BMD), 32 osteopenic postmenopausal women, and 25 osteoporotic postmenopausal
      women. The brachial-ankle PWV (baPWV) was measured using an automated device. The
      BMD of the lumbar spine (L2-L4) was measured using dual-energy X-ray
      absorptiometry. RESULTS: After adjusting for age and years since menopause, women
      with osteoporosis had a significantly higher baPWV than those with normal BMD
      (1500 +/- 220 cm/s versus 1340 +/- 215 cm/s; P < 0.05), but no significant
      differences in baPWV were seen between the osteoporotic and osteopenic groups or
      between the osteopenic and normal BMD groups. In univariate regression analysis,
      the baPWV was significantly negatively correlated with BMD (r = -0.450, P <
      0.01), and significantly positively correlated with age (r = 0.601, P < 0.01),
      years since menopause (r = 0.577, P < 0.01), systolic blood pressure (r = 0.295,
      P < 0.01), and diastolic blood pressure (r = 0.264, P < 0.05), but was not with
      other variables. In multivariate regression analysis, the baPWV was significantly
      correlated with BMD (P < 0.05), but not with other variables. CONCLUSIONS:
      Postmenopausal women with osteoporosis may have elevated arterial stiffness,
      suggesting that osteoporotic postmenopausal women may have a higher risk of
      cardiovascular disease.

PMID- 16621357
TI  - A novel white film for pharmaceutical coating formed by interaction of calcium
      lactate pentahydrate with hydroxypropyl methylcellulose.
AB  - We have found that a white film forms on tablets when a coating solution
      consisting of hydroxypropyl methylcellulose (HPMC), polyethylene glycol (PEG
      6000) and calcium lactate pentahydrate (CLP) is used. The white film has also
      been found in casting film consisting of HPMC and CLP, and the surface state of
      coated tablets has been shown to be strongly affected by addition of PEG 6000.
      The aim of the present study was to investigate the mechanism of formation of
      this white film in order to derive an appropriate film prescription. Interaction
      among the base ingredients of the film was investigated using differential
      scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform
      infrared (FT-IR) spectroscopy. The casting film formed with HPMC and a large
      excess of PEG 6000 was found to be crystalline in form. In contrast, the
      amorphous film consisting of HPMC, PEG 6000 and excess CLP exhibited the
      crystallinity film by an excess addition of CLP. Although the crystalline film
      had many cracks, the amorphous film appeared to be excellent as a tablet coating.
      The most probable interaction sites between HPMC and CLP were demonstrated by FT
      IR analysis of casting films consisting of HPMC, CLP and PVP.

PMID- 16621358
TI  - Hexosomes formed from glycerate surfactants--formulation as a colloidal carrier
      for irinotecan.
AB  - A new class of amphiphiles with a glycerate headgroup, recently shown to form
      reverse hexagonal phase in excess water, have been dispersed to form Hexosome
      dispersions comprising sub-200 nm particles retaining the internal nanostructure
      of the parent H(II) phase. The application of these novel materials to the
      development of a new injectable formulation of irinotecan was investigated. The
      formulation of irinotecan with a small percentage of oleic acid in oleyl
      glycerate permitted a clinically relevant dose of irinotecan to be dissolved in
      the glycerate surfactant and dispersed in aqueous medium to form an injectable
      particle-based dose form of irinotecan. Importantly, incorporation of irinotecan
      into Hexosomes at neutral pH did not result in conversion from the active lactone
      to the inactive carboxylate form on storage, and is hence a promising alternative
      to the current low pH formulation of irinotecan required to inhibit this
      conversion. Although release of irinotecan from the Hexosomes was shown to be
      virtually instantaneous from the Hexosomes on substantial dilution, the retention
      of the drug in lactone form at neutral pH demonstrates a potential application of
      these novel nanostructured particles in injectable drug delivery.

PMID- 16621359
TI  - Application of aerosol solvent extraction system (ASES) process for preparation
      of liposomes in a dry and reconstitutable form.
AB  - The aerosol solvent extraction system (ASES) process was applied to prepare
      liposomes in a dry and reconstitutable form. Dry ASES microparticles containing
      miconazole (MCZ) as a model drug were prepared by an optimized ASES process with
      various compositions of spraying solution containing phosphatidylcholine,
      cholesterol, and Poloxamer 407. The influence of such compositions and the pH of
      hydration medium on the physico-chemical properties of the produced
      microparticles were investigated before and after hydration. At optimized
      conditions, partially crystalline, spherical, and nonporous microparticles
      associated in aggregates varying from a few microns to 40 microm were produced
      with the residual content of methylene chloride and methanol lower than 30 and 86
      ppm, respectively. The percentage of drug recovered in the produced
      microparticles was increased with an increase of the drug concentration in the
      spraying solution. The entrapment efficiency of hydrated MCZ microparticles was
      improved by increasing the pH of the hydration medium.

PMID- 16621360
TI  - In vitro and in vivo characterization of nanoparticles made of MeO-PEG amine/PLA
      block copolymer and PLA.
AB  - The preparative method of a block copolymer of poly(dl-lactic acid) (PLA) and
      methoxypolyethylene glycol amine (MeO-PEG(N)), named PLA-(MeO-PEG), was refined.
      The degree of introduction of MeO-PEG(N) into PLA increased up to 55% (mol/mol)
      using a dichloromethane/methanol mixture (1:1, v/v) as a solvent at the reductive
      amination and taking all the fractions of the first peak in gel-chromatography.
      Plain and 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine (DiD)-loaded
      nanoparticles prepared using the PLA/PLA-(MeO-PEG) mixture of 45:55 (mol/mol)
      showed a mean size of 113 and 154 nm, respectively, and a positive zeta potential
      in water. DiD solution, i.v. administered, showed a lower plasma level and high
      distribution in liver, though DiD was distributed into the blood cells to a fair
      extent. Nanoparticles exhibited a higher plasma concentration of DiD than the DiD
      solution at 1 and 8h, though DiD was distributed into the liver and spleen to a
      fair extent. Nanoparticles made of the PLA/PLA-(MeO-PEG) mixture of 44:55
      (mol/mol) showed better plasma retention than those made of the PLA/PLA-(MeO-PEG)
      mixture of 64:36 (mol/mol). It is suggested that the PLA/PLA-(MeO-PEG) mixture
      nanoparticles with a higher PEG/PLA ratio should be useful as a carrier for the
      elevation of the plasma concentration of lipophilic drugs.

PMID- 16621361
TI  - Zero-order release of aspirin, theophylline and atenolol in water from novel
      methylcellulose glutarate matrix tablets.
AB  - A novel hydrocolloidal polymer, methylcellulose glutarate (MC-GA), was prepared
      by esterifying methylcellulose with glutaric anhydride. The formation of ester
      was confirmed by FTIR and NMR spectroscopy, DSC and elemental analysis. The
      physicochemical properties such as, rate of swelling in water, viscosity and
      hygroscopicity of MC-GA were determined and compared with those of methycellulose
      A (MC). Aspirin, theophylline and atenolol tablets were compacted on a Carver
      press using the wet granulation method. Each tablet contained: 200 mg active, 80
      mg anhydrous lactose, 8 mg povidone, 4 mg magnesium stearate, 4 mg talc, 50mg MC
      or MC-GA (drug-to-polymer ratio, 4:1). Contrary to the first-order release
      profile of all the drugs from the MC matrix tablets, a zero-order release was
      obtained from the MC-GA matrix tablets in water.

PMID- 16621362
TI  - Controlled drug release from Gelucire-based matrix pellets: experiment and
      theory.
AB  - The aim of this work was to elucidate the underlying drug release mechanisms from
      lipidic matrix pellets, using theophylline and Gelucire 50/02 as model drug and
      carrier material, respectively. Pellets were prepared by two different
      techniques: melt-solidification and extrusion-spheronization. The effects of
      different formulations and processing parameters on the resulting drug release
      kinetics in 0.1N HCl and phosphate buffer pH 7.4 were studied and the obtained
      results analyzed using adequate mathematical models in order to get further
      insight into the underlying mass transport mechanisms. The type of preparation
      technique was found to strongly affect the underlying drug release mechanisms.
      Drug release from pellets prepared by the melt-solidification method was
      primarily controlled by pure diffusion, whereas drug release from pellets
      prepared by the extrusion-spheronization method was purely diffusion-controlled
      only at early time points. After approximately 2h, the pellets started to
      disintegrate, resulting in decreased diffusion pathway lengths and, thus,
      increased drug release rates. Furthermore, the curing conditions significantly
      affected the theophylline release kinetics, whereas varying the initial drug
      loading from 20 to 50% (w/w) resulted only in a slight increase in the relative
      drug release rate. Interestingly, the effects of the size of pellets prepared by
      the melt-solidification method on the resulting drug release kinetics could be
      quantitatively predicted using an analytical solution of Fick's second law of
      diffusion. These predictions could be verified by independent experiments.

PMID- 16621363
TI  - Characterising the size and shape of polyamidoamines in solution as a function of
      pH using neutron scattering and pulsed-gradient spin-echo NMR.
AB  - Bioresponsive polymers are being developed as synthetic viral mimetics to enhance
      the intracellular delivery of macromolecular therapeutic agents such as genes,
      proteins and peptides. In this context we have designed pH-responsive, amphoteric
      polyamidoamines (PAAs) which change conformation on passing from a neutral pH
      (extracellular) to an acidic pH (endosomal and lysosomal) environments. PAAs have
      already demonstrated cytosolic delivery of genes and non-permeant toxins (e.g.
      gelonin and ricin A chain). The aim of this study was to use small-angle neutron
      scattering (SANS) to investigate the most likely shape of the hydrochloride salt
      form of one particular PAA (ISA23) in solution, under pH conditions that mimic
      those the polymer would be expected to encounter during endocytic internalisation
      (pH 7.4-3). It was shown that models based on a Gaussian coil representation of
      the polymer conformation described the SANS data better over this pH range than
      models based on a rod-like conformation. The conformation of ISA23 at 37 degrees
      C was expanded (radius of gyration approximately 80A) at pH approximately 3 but
      collapsed with an increase in pH (radius of gyration approximately 20A at pH
      7.4), a conclusion also reached in a model-free analysis of the neutron data.
      Outside this pH range - at the extremes of high and low pH - the polymer coil
      collapsed and interpretation of the scattering was slightly complicated by the
      presence of a very weak structure factor indicating that the polymer coils are
      highly charged. The PAA concentration did not significantly affect the polymer
      size over the concentration range 10-50mg/ml. Characterisation of the dynamics of
      these polymer solutions - diffusion coefficients and viscosity -ostensibly
      suggest a very different conclusion with the polymer expanding as the pH is
      increased, but this arises due to weak aggregation of the amphoteric polymer
      coils.

PMID- 16621364
TI  - High throughput microsomal stability assay for insoluble compounds.
AB  - High throughput metabolic stability assays are widely implemented in drug
      discovery to guide structural modification, predict in vivo performance, develop
      structure-metabolic stability relationships, and triage compounds for in vivo
      animal studies. However, these methods are often developed and validated using
      commercial drugs. Many drug discovery compounds differ from commercial drugs,
      with many having high lipophilicity, high molecular weight and low solubility.
      The impact of very low solubility on metabolic stability assay results was
      explored. Two metabolic stability assays, the 'aqueous dilution method' and the
      'cosolvent method, were compared. For commercial drugs and most discovery
      compounds having reasonable drug-like properties, the two methods gave comparable
      results. For highly lipophilic, insoluble drug discovery compounds, the 'aqueous
      dilution method' gave artificially higher stability results. The cosolvent method
      performs compound dilutions in solutions with higher organic solvent content and
      adds solutions directly to microsomes to assist with solubilization, minimize
      precipitation and reduce non-specific binding to plastics. This method is more
      applicable in drug discovery where compounds of a wide range of solubility are
      studied.

PMID- 16621365
TI  - Investigation of factors responsible for low oral bioavailability of cefpodoxime
      proxetil.
AB  - Learning about the behavior of a drug in biological environment enables
      application of better formulation strategies to improve bioavailability of the
      same. Cefpodoxime proxetil (CP) is a prodrug, which is orally administered
      cephalosporin with only 50% absolute bioavailability. Despite previous studies,
      reasons responsible for low bioavailability of CP remain poorly understood. The
      present study tries to ascertain reasons for the low oral bioavailability of CP.
      The in vitro, in situ and ex vivo studies showed interesting results, where
      metabolism of CP into cefpodoxime acid (CA) inside the intestinal epithelial cell
      and preferential efflux of CA into lumen was identified as primary reason for low
      oral bioavailability of CP. Presence of specific carriers or transportation
      mechanism on the apical side membrane of enterocyte, than basal side of the same
      was observed.

PMID- 16621366
TI  - Gels as vaginal drug delivery systems.
AB  - The vagina has been used as a mucosal drug delivery route for a long time. Its
      single characteristics can be either limitative or advantageous when drug
      delivery is considered. Gels are semi-solid, three-dimensional, polymeric
      matrices comprising small amounts of solid, dispersed in relatively large amounts
      of liquid, yet possessing more solid-like character. These systems have been used
      and are receiving a great deal of interest as vaginal drug delivery systems. Gels
      are versatile and have been used as delivery systems for microbicides,
      contraceptives, labour inducers, and other substances. Although somewhat
      neglected in clinical studies, pharmaceutical characterization of vaginal gels is
      an important step in order to optimize safety, efficacy and acceptability.
      Indeed, the simple formulation of a gel can lead to different performances of
      systems containing the same amount of active substances. Therefore, this paper
      discusses and summarizes current use and research of vaginal drug delivery
      systems based in gels.

PMID- 16621367
TI  - Lectin anchored stabilized biodegradable nanoparticles for oral immunization 1.
      Development and in vitro evaluation.
AB  - The investigation comprises development of a stable and targeted formulation of
      HBsAg for the oral immunization against Hepatitis B. PLGA nanoparticles bearing
      HBsAg was prepared by double emulsion method. The antigen was protected from
      organic/aqueous interface by using protein stabilizer, trehalose. The acidic
      environment generated within PLGA nanoparticles was neutralized by co
      encapsulation of a basic additive, Mg(OH)(2) which provides an additional
      stabilization to the antigen especially against acid induced antigen
      inactivation. Furthermore, lectin from Arachis hypogaea (PNA) was anchored on to
      the surface of the HBsAg loaded nanoparticles in order to enhance their affinity
      towards the antigen presenting cells of the Peyer's patches. The developed system
      was characterized for shape, size and loading efficiency. The antigen integrity
      was assessed by using SDS-PAGE followed by isoelectric focusing analysis. Bovine
      submaxillary mucin (BSM) was used as a biological model for in vitro ligand
      affinity determination and activity studies. The lectin anchored nanoparticles
      exhibited 52.18+/-4.73% loading while ligand density was estimated to be of
      17.90+/-1.14 microg/mg. The results suggest that HBsAg can be successfully
      stabilized by co-encapsulation of an appropriate protein stabilizer, i.e.
      trehalose and a basic additive, Mg(OH)(2). The ligand-coupled nanoparticles
      demonstrated approximately four folds increase in degree interaction with the BSM
      as compared to plain nanoparticles. Additionally, the nanoparticles maintained
      their intrinsic sugar specificity as associated due to lectin (PNA).

PMID- 16621368
TI  - Inhibitory effects of statins on human monocarboxylate transporter 4.
AB  - Human MCT4 (SLC16A3) is responsible for the efflux of L-lactic acid from skeletal
      muscle cells and is essential for muscle homeostasis. However, the effects of
      monocarboxylate drugs, such as statins on the MCT4-mediated transport of L-lactic
      acid have not been elucidated. Inhibition of L-lactic acid transport mediated by
      MCT4 might to lead to collapse of muscle homeostasis. The aim of this study was
      to establish an MCT4 transfected cell line and to clarify the transport mechanism
      of L-lactic acid and the effects of statins on this transport system. Results of
      Western blot analyses and immunohistochemistry studies indicated that the
      expression of CD147 and MCT4-FLAG protein were observed and was displayed clear
      plasma membrane localization in CD147 and MCT4-FLAG co-transfected cell line (cm
      cells). Uptake of L-lactic acid in cm cells was significantly greater than that
      in cells transfected with a vector alone. L-lactic acid uptake was concentration
      dependent with a K(m) value of 28.43+/-3.87 mM. The results of a previous study
      showing a K(m) value of 28.5 mM in hMCT4-expressed oocytes. Lipophilic statins
      significantly inhibited [(14)C] L-lactic acid uptake in a concentration-dependent
      manner. In contrast, the inhibitory effects of hydrophilic statins were very
      weak.

PMID- 16621369
TI  - Recombinant human parathyroid hormone 1-34: pharmacokinetics, tissue distribution
      and excretion in rats.
AB  - The objective of this work was to characterize the preclinical pharmacokinetics,
      tissue distribution, and excretion profiles of recombinant human parathyroid
      hormone (1-34) [rhPTH (1-34)] in healthy rats. Pharmacokinetic properties of
      (125)I-rhPTH (1-34) were examined after a single subcutaneous (s.c.) and
      intravenous (i.v.) bolus injection, respectively. Tissue distribution and
      urinary, fecal, and biliary excretion patterns of (125)I-rhPTH (1-34) were also
      investigated following a single s.c. injection. Our results suggested that rhPTH
      (1-34) was rapidly distributed and cleared in a bi-exponential manner after a
      single i.v. bolus injection. Following a single s.c. administration, rhPTH (1-34)
      exhibited rapid and considerable absorption and declined in a mono-exponential
      manner, with the absolute bioavailability and elimination half-life of 65% and
      3.4-4.1h, respectively. The TCA-precipitated radioactivity was widely distributed
      and rapidly diminished in most tissues/organs. Approximately 91% and 2% of the
      total radioactivity was recovered in urine and feces by 72h postdosing,
      respectively; whereas 6% excreted into bile up to 24h postdosing. These findings
      indicated high absolute bioavailability, rapid absorption and disposition of
      rhPTH (1-34) following a single s.c. administration in healthy rats. The
      accumulation of rhPTH (1-34) in tissues/organs examined appeared to be low. The
      major elimination route was urinary excretion.

PMID- 16621370
TI  - Arsenic release from glass containers by action of intravenous nutrition
      formulation constituents.
AB  - Pharmacopoeias prescribe tests to determine the levels of arsenic in raw
      materials and glass containers. In this study, glass ampoules for injectables
      containing individually the main components of intravenous nutrition formulations
      were submitted to the hydrolytic resistance test by heating at 121 degrees C for
      30 min. As(V) and As(III) levels in these solutions after heating were determined
      by hydride generation atomic absorption spectrometry. The arsenic content of
      substances used in these formulations was previously determined, as well as the
      arsenic content of the glass containers. The results showed that raw substances
      as well as glass containers contain arsenic. Moreover, arsenic is released during
      the heating (hydrolytic resistance test). However, the amount released and the
      arsenic species present in solution depend on the solution composition. While
      As(V) was the predominant specie in glass, solutions containing reducing
      substances such as glucose and vitamins had As(III) in higher concentration.
      Therefore, arsenic is released from glass containers during the heating for
      sterilization, and reacts with formulation constituents depending on their
      reducing properties.

PMID- 16621371
TI  - Mechanical property anisotropy of pharmaceutical excipient compacts.
AB  - The mechanical property anisotropy of compacts made from six commercially
      available pharmaceutical excipient powders was evaluated. Uni-axially compressed
      cubic compacts of each excipient were subjected to pendulum impact testing and
      transverse tensile testing in several orientations. The pendulum impact test was
      used to measure the dynamic indentation hardness of each compact face (side, top,
      and bottom). Transverse tensile testing was utilized to determine the compact
      axial and radial tensile strength values. The indentation hardness
      (top>bottom>side) and tensile strength tests (radial>axial) revealed mechanical
      property anisotropy in all the compacts. The extent of mechanical property
      anisotropy was quantified by using dimensionless ratios and was found to be
      significantly different for each material. In general, compacts with a higher
      degree of compact mechanical anisotropy also exhibited a higher brittle fracture
      index (BFI). This suggests that the macroscopic flaws intentionally made in the
      compact for the BFI measurement were similar to the flaws induced in highly
      anisotropic materials during uni-axial compaction. These results are consistent
      with the practical observation that brittle materials are more likely to exhibit
      failure in a plane normal to the compaction axis, i.e. experience tablet capping
      and lamination phenomena.

PMID- 16621372
TI  - Xanthine oxidase inhibitory activity of Lychnophora species from Brazil
      ("Arnica").
AB  - Twenty-two extracts from five Lychnophora species and one Lychnophoriopsis
      species, traditionally used in Brazil as analgesic, anti-inflammatory, and to
      treat bruise and rheumatism were examined for the inhibition of xanthine oxidase
      (XO), the enzyme that catalyses the metabolism of hypoxanthine and xanthine into
      uric acid. Sixteen extracts were tested. All of them were found to have excellent
      XO inhibitory activity, with inhibitions greater than 38% at 100 microg/mL in the
      assay mixture. The most active plants examined were Lychnophora trichocarpha,
      Lychnophora ericoides, Lychnophora staavioides and Lychnophoriopsis candelabrum,
      with inhibitions of 77%, 78%, 66% and 63% at 100 microg/mL, respectively, and
      IC(50) values of 6.16, 8.28, 33.97 and 37.70 microg/mL, respectively.

PMID- 16621373
TI  - Disease-Consensus Index as a tool of selecting potential hypoglycemic plants in
      Chikindzonot, Yucatan, Mexico.
AB  - There is a general lack of adequate methods to quantitatively assess the
      importance of specific medicinal plants in a culture. In Mexico like in many
      other countries type 2 diabetes is an increasing health problem and the use of
      medicinal plants to treat this disease is widespread. In the present study we
      propose a mathematical tool for analysing ethnopharmacological field data, with
      the ultimate aim to select species with most prominent impact on a community to
      treat a single disease. Using this tool in a Yucatec Mayan community we
      demonstrate that Malmea depressa (Baill.) R.E. Fr. and Cecropia peltata L. are
      culturally most salient hypoglycemic plants in this community.

PMID- 16621374
TI  - Analgesic and sedative activities of lactucin and some lactucin-like guaianolides
      in mice.
AB  - Lactucin (1) and its derivatives lactucopicrin (2) and 11beta,13-dihydrolactucin
      (3), which are characteristic bitter sesquiterpene lactones of Lactuca virosa and
      Cichorium intybus, were evaluated for analgesic and sedative properties in mice.
      The compounds showed analgesic effects at doses of 15 and 30 mg/kg in the hot
      plate test similar to that of ibuprofen, used as a standard drug, at a dose of 30
      mg/kg. The analgesic activities of the compounds at a dose of 30 mg/kg in the
      tail-flick test were comparable to that of ibuprofen given at a dose of 60 mg/kg.
      Lactucopicrin appeared to be the most potent analgetic of the three tested
      compounds. Lactucin and lactucopicrin, but not 11beta,13-dihydrolactucin, also
      showed sedative properties in the spontaneous locomotor activity test.

PMID- 16621375
TI  - Hepatoprotective effects of Pittosporum neelgherrense Wight&Arn., a popular
      Indian ethnomedicine.
AB  - The stem bark of Pittosporum neelgherrense Wight&Arn. is used by the Kani and
      Malapandaram tribes of Kerala as an effective antidote to snake bite and for the
      treatment of various hepatic disorders. In the present study, the effect of the
      methanolic extract of the stem bark of Pittosporum neelgherrense was studied
      against carbon tetrachloride (CCl(4))-, d-galactosamine (D-GalN)- and
      acetaminophen (APAP)-induced acute hepatotoxicity in Wistar rats. Significant
      hepatoprotective effects were obtained against liver damage induced by all the
      three liver toxins, as evident from decreased levels of serum enzymes, glutamate
      oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT) and an
      almost normal architecture of the liver in the treated groups, compared to the
      toxin controls. Thus the present study provides a scientific rationale for the
      traditional use of this plant in the management of liver diseases.

PMID- 16621376
TI  - Characterization of cysteine proteases in Malian medicinal plants.
AB  - Extracts form 10 different Malian medicinal plants with a traditional use against
      schistosomiasis were investigated for their possible content of proteolytic
      activity. The proteolytic activity was studied by measuring the hydrolysis of two
      synthetic peptide substrates Z-Ala-Ala-Asn-NHMec and Z-Phe-Arg-NHMec. Legumain-
      and papain-like activities were found in all tested crude extracts except those
      from Entada africana, with the papain-like activity being the strongest. Cissus
      quadrangularis, Securidaca longepedunculata and Stylosanthes erecta extracts
      showed high proteolytic activities towards both substrates. After gel filtration
      the proteolytic activity towards the substrate Z-Ala-Ala-Asn-NHMec in root
      extract of Securidaca longepedunculata appeared to have Mr of 30 and 97kDa, while
      the activity in extracts from Cissus quadrangularis was at 39kDa. Enzymatic
      activity cleaving the substrate Z-Phe-Arg-NHMec showed apparent Mr of 97 and
      26kDa in extracts from roots and leaves of Securidaca longepedunculata, while in
      Cissus quadrangularis extracts the activity eluted at 39 and 20kDa, with the
      highest activity in the latter. All Z-Phe-Arg-NHMec activities were inhibited by
      E-64 but unaffected by PMSF. The legumain activity was unaffected by E-64 and
      PMSF. The SDS-PAGE analysis exhibited five distinct gelatinolytic bands for
      Cissus quadrangularis extracts (115, 59, 31, 22 and 20kDa), while two bands (59
      and 30kDa) were detected in Securidaca longepedunculata extracts. The inhibition
      profile of the gelatinolytic bands and that of the hydrolysis of the synthetic
      substrates indicate the cysteine protease class of the proteolytic activities.
      Several cysteine protease activities with different molecular weights along with
      a strong variability of these activities between species as well as between plant
      parts from the same species were observed.

PMID- 16621377
TI  - Anti-inflammatory activities of the triterpene acids from the resin of Boswellia
      carteri.
AB  - Boswellic acids are the main well-known active components of the resin of
      Boswellia carteri (Burseraceae) and these are still dealing with the
      ethnomedicinal use for the treatment of rheumatoid arthritis and other
      inflammatory diseases. Although several studies have already been reported on the
      pharmacological properties, especially on the anti-inflammatory activity, of
      Boswellia carteri resin and boswellic acids, the ethnomedicinal importance of
      Boswellia carteri and its components, boswellic acids, prompted us to undertake
      detailed investigation on the constituents of the resin and their anti
      inflammatory activity. Fifteen triterpene acids, viz., seven of the beta
      boswellic acids (ursane-type) (1-7), two of the alpha-boswellic acids (oleanane
      type) (8, 9), two of the lupeolic acids (lupane-type) (10, 11), and four of the
      tirucallane-type (12-14, 16), along with two cembrane-type diterpenes (17, 18),
      were isolated and identified from the methanol extract of the resin of Boswellia
      carteri. Upon evaluation of 17 compounds, 1-14 and 16-18, and compound 15, semi
      synthesized from 14 by acetylation, for their inhibitory activity against 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in
      mice, all of the compounds, except for 18, exhibited marked anti-inflammatory
      activity with a 50% inhibitory dose (ID(50)) of 0.05-0.49 mg/ear.

PMID- 16621378
TI  - The effect of medicinal plants used in Chinese folk medicine on RANTES secretion
      by virus-infected human epithelial cells.
AB  - The accumulation of inflammatory cells in the infective sites has been reported
      to play a crucial role in the progression of chronic inflammation and multiple
      sclerosis after viral infection. In the present study, nine ethanol extracts of
      Forsythia suspensa Vahl. (Oleaceae), Lonicera japonica Thunb. (Caprifoliaceae),
      Isatis indigotica Fort. (Cruciferae), Strobilanthes cusia (Ness.) O. Kuntze
      (Acanthaceae), Astragalus membranaceus (Fisch.) Bge. (Leguminosae), Hedysarum
      polybotrys Hand.-Mazz. (Leguminosae), Andrographis paniculata (Burm. f.) Ness.
      (Acanthaceae), Glycyrrhiza uralensis Fischer. (Leguminosae) and Ligusticum
      wallichii Franch. (Umbelliferae), medicinal plants traditionally used in China
      for treating conditions likely to be associated with inflammation and viral
      infection, were screened for their effect on RANTES secretion by influenza A
      virus (H1N1)-infected human bronchial epithelial cells (A549). With exception of
      Lonicera japonica, Isatis indigotica, Astragalus membranaceus and Hedysarum
      polybotrys, all plants tested at concentration of 200 microg/ml possessed more
      than 50% suppressing effect on RANTES secretion by H1N1-infected A549 bronchial
      epithelial cells. Among the plants tested, Andrographis paniculata showed the
      most promising property to inhibit RANTES secretion with an IC(50) of 1.2 +/- 0.4
      microg/ml while the next two were Glycyrrhiza uralensis and Forsythia suspensa
      (IC(50) ranging from 35 to 48 microg/ml).

PMID- 16621379
TI  - From cnidarians to mammals: the use of animals as remedies in fishing communities
      in NE Brazil.
AB  - This work documents zootherapeutic practices in Northeast Brazil. It is primarily
      based on field surveys carried out in fishing villages located in the states of
      Maranhao and Paraiba, where 60 respondents (38 men and 22 women) provided
      information on animal species used as medicine, body parts used to prepare the
      remedies and illnesses to which the remedies were prescribed. A total of 100
      animal species (72 families), distributed in 12 taxonomic categories, was used as
      medicine. Zootherapeutic resources were used to treat 62 different diseases. The
      local medicinal fauna is largely based on wild animals, including some endangered
      species. Threatened species, such as the seahorse (Hippocampus reidi, Ginsburg,
      1933) (Syngnathidae) and the green turtle (Chelonia mydas, Linnaeus, 1758)
      (Cheloniidae) represented important medicinal resources for the studied
      communities. This shows the need to integrate traditional knowledge into
      strategies to conserve and manage faunistic resources in Brazil.

PMID- 16621380
TI  - Genetic polymorphisms of 15 STR loci in two Tibetan populations from Tibet
      Changdu and Naqu, China.
AB  - The allelic distribution of 15 short tandem repeat (STR) loci included in the
      AmpFl STR Identifiler kit was examined in 100 Changdu Tibetan and 118 Naqu
      Tibetan unrelated individuals living in the Tibet Province, PR China. The
      distribution of these observed genotypes was not significantly different from the
      expected distribution according to Hardy-Weinberg equilibrium.

PMID- 16621381
TI  - Forensic analysis of soil and sediment traces by scanning electron microscopy and
      energy-dispersive X-ray analysis: an experimental investigation.
AB  - This paper reports the results of a series of experiments carried out to
      determine the precision of soil trace comparisons based on elemental peak height
      ratios determined by energy-dispersive X-ray analysis (EDXRA) in a variable
      pressure scanning electron microscope (VP-SEM). Experiments were conducted on
      'bulk' soil aggregates, ground powders prepared from the <150 microm soil
      fractions and on smears of both the bulk soil and <150 microm material placed on
      cotton cloth. X-ray count data were obtained using area scans and spot analyses
      at different magnifications. The effects on elemental peak height ratios of
      varying the SEM chamber pressure, beam spot size, emission current and
      accelerating voltage were also examined. The peak height ratios for oxygen,
      silicon, aluminium, potassium, calcium and iron were found to show little
      variation as a function of chamber pressure, spot size and emission current over
      the ranges examined, but a strong dependency on accelerating voltage was
      observed. Within-sample variation in results, expressed by the percentage
      coefficient of variation, was found to be lowest for area scan analyses of the
      ground <150 microm fractions and greatest for the spot analyses of the bulk soil
      aggregates and the <150 microm fractions. We conclude that comparison of
      elemental peak height ratios determined by EDXRA can be a useful tool for rapid
      screening of soil samples, especially when combined with investigation of other
      attributes of the soil traces such as colour, fabric and the composition, shapes
      and surface textures of individual particles or aggregates within the soil
      traces. If sufficient material is available and can be readily separated without
      contamination or loss, higher resolution and more precise elemental data should
      be obtained by methods such as inductively coupled plasma atomic-emission
      spectrometry (ICP-AES) or mass-spectrometry (ICP-MS).

PMID- 16621382
TI  - The recovery of illicit drugs from oral fluid sampling devices.
AB  - Testing for drugs in oral fluid is a convenient procedure for determining recent
      drug use. A number of issues are still to be resolved and this paper investigates
      the effects of storage systems on drug stability and recovery using three
      different collection devices supplied by Cozart, Immunalysis and Microgenics
      (third party). Drugs were analysed using a range of immunoassay systems followed
      by MS confirmation and quantitation. The reproducibility of the weight of
      specimen collected was excellent (CV<10%) for the three collection devices
      tested. Of the three systems studied, only the Cozart product gave acceptable
      recovery of THC from drug-spiked oral fluid. A combination of Cozart, Immunalysis
      and Diagnostix immunoassays with the Cozart collection system gave the most
      sensitive and discriminating screening assays for the drugs studied, namely THC,
      benzodiazepines, methamphetamine and morphine. Storage at either 5 degrees C or
      room temperature had no significant effect on drug recoveries.

PMID- 16621383
TI  - A rapid and convenient LC/MS method for routine identification of
      methamphetamine/dimethylamphetamine and their metabolites in urine.
AB  - A rapid and sensitive LC/MS method was developed for the simultaneous analysis of
      N,N-dimethylamphetamine (DMA), N,N-dimethylamphetamine N-oxide (DMANO),
      methylamphetamine (MA) and amphetamine (A) in urine samples. Employing an Alltech
      C18 column for solid phase extraction followed by LC/MS analysis using an Alltech
      Platinum EPS C18 column with a mixture of ammonium formate (0.01 M, pH 3) and
      acetonitrile (77:23, v/v) as mobile phase at a flow rate of 0.2 mL/min,
      simultaneous identification and quantitation of A, MA, DMA and DMANO in urine can
      be achieved using a 5-min chromatographic run. The calibration ranges were 0.10
      3.0 micro g/mL for DMANO, 0.05-3.0 micro g/mL for DMA and 0.05-5.0 micro g/mL for
      both MA and A. The intra-, inter-day precision and accuracy for all analytes,
      spiked at three different concentrations in quality control samples, were in the
      ranges of 1.7-8.6, 4.1-10.0, -11.6 to 12.9%, respectively. The newly developed
      method was applied to the analysis of urine samples obtained from 118 suspected
      MA/DMA abusers, with the presence of MA confirmed in their urine samples under
      the drug-use surveillance program. Of these 118 samples, 43 were found to contain
      DMANO and 11 with both DMANO and DMA.

PMID- 16621384
TI  - Identify the injury implements by SEM/EDX and ICP-AES.
AB  - The forensic investigator is frequently confronted with the discrimination and
      deduction of injury implements, which is one of the most important physical
      testimonies in courts. The usual method used in actual cases is from points of
      morphology. In the forensic discrimination of injury implements, such as metal
      implements, the analysis and comparison of elements are expected to provide
      excellent results, and simultaneous multi-elemental analysis is required to
      analyze various kinds of elements. This study was designed to establish
      discrimination and deduction of metal injury implements by scanning electron
      microscope/energy disperse X-ray microanalyzer (SEM/EDX) and inductively coupled
      plasma atomic emission spectrometry (ICP-AES). Examined metal particles in five
      wounds made on the skin of domestic pigs, respectively, using Cu-Zn or Cr-Ni
      coated and carbon steel kitchen implements by EDX. For carbon steel kitchen
      implements, analyzed five samples from the back and blade separately in the
      contents and varieties of elements by ICP-AES. In the wounds by the coated
      implements, the special particles only containing Cu, Zn or Cr, Ni were found. In
      the wounds by carbon steel kitchen implements, the particles containing Fe, Cr,
      Si or Fe, Mn, Si were found. The differences of contents of elements between the
      back and blade was no significant except No. 5 for carbon steel kitchen
      implements, and the significant differences of elements exited in Cr, Mn, Si, Cu,
      Mo among the stainless kitchen knives, Mn, Si among the other kitchen implements
      and for the blade of No. 5 knife, relative standard deviations (R.S.D.s) were
      significantly different in Mn, Si, Mo, Ti, S, P, Ni. Using EDX to examine the
      particles in wounds can deduce the categories of metal injury implements, and we
      can still deduce the different implements in the same category by ICP-AES.

PMID- 16621385
TI  - The relationship between bedding and face-down death in infancy: mathematical
      analysis of a respiratory simulation system using an infant mannequin to assess
      gas diffusibility in bedding.
AB  - Rebreathing is a model for the relationship between a prone sleeping position and
      sudden infant death syndrome. This study used a mechanical simulation model to
      establish the relationship between types of bedding and rebreathing potential for
      an infant placed prone (face down) at different postnatal ages. The infant
      mannequin was connected to a respirator set to deliver physiologically
      appropriate combinations of tidal volume (V(T)) and respiratory rates (RR) across
      a range of postnatal ages (0-18 months). Before measurements were made, CO(2)
      flow was regulated to 5+/-0.1% of end-tidal PCO(2) (EtCO(2)). After the model was
      placed in a prone position, any increase in the fractional concentration of
      inspired CO(2) (FiCO(2)) was measured. FiCO(2) increased immediately and rapidly,
      and reached a maximum value within a few minutes. The maximum FiCO(2) ranged from
      under 2% to over 10%, depending on the bedding. FiCO(2) was also affected by V(T)
      and RR. This model is not applicable to actual infants because of the large
      tissue stores of CO(2) in infants; however, it is useful for evaluation of gas
      diffusibility of bedding and will simplify the investigation of sleeping
      environments when a baby is found dead with its face covered by soft bedding. In
      general, the higher the FiCO(2), the greater the rebreathing potential.
      Theoretically, considering the paucity of body stores of O(2), changes in FiO(2)
      would be affected not by changes in FiCO(2), but by CO(2) production and gas
      movement around the infant's face. The rapid decrease of FiO(2) is approximated
      at the inverse of the FiCO(2) timecourse, suggesting the significance of not only
      CO(2) accumulation but also O(2) deprivation in the potential space around the
      baby's face.

PMID- 16621386
TI  - Allele frequencies for 15 STR loci in Tibetan populations from Nepal.
AB  - Samples from 105 unrelated healthy Sherpa in Namche Bazaar and 111 unrelated non
      Sherpa in Kathmandu valley from Nepal were used to obtain allele frequency data
      for 15 short tandem repeat (STR) loci (CSF1PO, D2S1338, D3S1358, D5S818, D7S820,
      D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, TH01, TPOX and vWA)
      included in the AmpFLSTR Identifiler kit. No deviations from Hardy-Weinberg
      equilibrium were observed, but only after applying a Bonferroni correction in the
      case of D5S818 in the Sherpa population and D7S820 in the Kathmandu population.
      Genetic parameters of forensic interest were calculated and genetic
      differentiation between the two populations tested.

PMID- 16621387
TI  - Keynote lecture: an update on the what, why and how questions of ageing.
AB  - In this keynote address, we briefly consider three global questions on the
      biology of ageing. What is it? While it is certainly the case that development
      has a major impact upon ageing, gerontologists characterize ageing as gradual,
      insidious, post-maturational declines in the structure and function of multiple
      organ systems, certainly to include reproduction. This is accompanied by
      increasing rates of mortality within populations. Comprehensive, longitudinal
      physiological assessments are not commonly pursued in their experiments, however;
      this deficiency limits one's ability to interpret the results of putative
      interventions. Why does it happen? Although subject to recent challenges, the
      most satisfying explanation for inter-specific variations in longevity is given
      by the evolutionary biological theory of ageing. Life history parameters,
      including longevity, are molded by the ecological forces in which the species
      evolves. How does it happen? To gain insight into fundamental mechanisms of
      ageing, we have focused upon classes of gene actions that, according to the
      evolutionary theory, can escape the forces of natural selection.

PMID- 16621388
TI  - Aging aggravates heterogeneities in cell-size and stress-intolerance of cardiac
      ventricular myocytes.
AB  - RATIONALE: Heterogeneity of ventricular myocytes from old murine hearts was
      tested in regard to cell volume and tolerance to stress induced by ROS generated
      by photoactivation of tetramethylrhodamine methylester. RESULTS: During
      repetitive linescans, ROS generated 'scars' of depolarized mitochondria. All
      young and 60% of old myocytes had type1 scars that were small and remained stable
      with time. Forty percent cells from old hearts responded with type2 scars that
      were wide and expanded with time. Depolarization of individual mitochondria was
      characterized by its half decay time. HDT was 6.9s in young mice (type1
      mitochondria). HDT was 5.6s in old mice due to a 30% population of mitochondria
      with reduced ROS-tolerance (type2, HDT=3.0 s). Type1 and type2 mitochondria did
      not coexist in the same cell, however, in the same old heart (different
      myocytes). In a different set of myocytes the volumes were measured to be larger
      (83+/-29 pl) and more heterogeneous than in young myocytes (49+/-13 pl).
      CONCLUSION: Hearts of old mice contain a subpopulation of myocytes with reduced
      mitochondrial stress-tolerance that is attributed to an age-dependent reduction
      of cellular ROS defence capacity. We discuss how heterogeneities in stress
      tolerance and cell volume could be causally linked.

PMID- 16621389
TI  - Heart failure in elderly patients.
AB  - Several structural and functional changes contribute to heart failure in elderly
      patients: an age dependent increase in sympathetic nervous activity, left
      ventricular wall diameter, myocardial fibrosis and apoptosis, micro- and
      macrovascular coronary sclerosis, aortic stiffness. As a consequence, diastolic,
      but also systolic heart failure is a frequent finding in elderly patients. The
      relation of systolic to diastolic heart failure is clearly shifted towards
      diastolic heart failure in elderly patients, especially in women. Mortality is
      increased with systolic dysfunction in elderly patients compared to younger heart
      failure patients. Mortality is less with diastolic dysfunction, but still higher
      compared to elderly without heart failure. In addition, morbidity is increased
      both with diastolic and systolic heart failure in elderly patients. Cognitive
      dysfunction is a frequent finding. After exclusion of specific cardiac and
      extracardiac reasons for dyspnoea, drug therapy of systolic heart failure in
      elderly is similar to younger patients. However, the physiological decrease of
      renal function and the more frequent renal impairment in elderly patients with
      heart failure needs to be considered. Guideline recommendations for drug therapy
      are based in most cases on studies conducted in younger systolic heart failure
      patients. A recent meta-analysis of randomized beta-blocker trials suggests
      improved survival with beta-blockers even in the elderly subgroup. Guidelines for
      the treatment of diastolic heart failure are available only recently. The term
      heart failure with normal left ventricular ejection fraction (LVEF) has been
      proposed instead of diastolic heart failure. Given the increased morbidity and
      mortality in elderly patients with heart failure and normal LVEF, therapy should
      include general measures, such as physical activity, weight reduction, volume
      restriction. Specific therapy includes optimal control of systolic and diastolic
      blood pressure, diuretics, nitrates, and frequency-control. However, randomized
      trials evaluating the efficacy of specific therapies in heart failure with normal
      LVEF are still missing.

PMID- 16621390
TI  - Accumulation of altered proteins and ageing: causes and effects.
AB  - Accumulation of altered proteins is the most common molecular symptom of ageing.
      Altered proteins are also associated with many age-related pathologies. Altered
      proteins are continuously produced but are normally selectively degraded by
      cellular proteases; their accumulation during ageing may be explained by either
      or both increased production or decreased elimination. Sources of altered
      proteins include erroneous synthesis by cytoplasmic and mitochondrial ribosomes,
      spontaneous deamidation, isomerization and racemization of unstable amino acids
      residues, damage inflicted by reactive oxygen and nitrogen species, and glycation
      and cross-linking by glucose and more reactive metabolites. Glycated proteins may
      damage mitochondria to increase production of reactive oxygen species, while
      highly oxidised/cross-linked polypeptides may resist proteolysis, inhibit
      proteasome function and induce a permanent stress response. Other possible
      explanations for the age-related changes in the defence systems, enzymatic and
      non-enzymatic, which normally counter generation of altered proteins are also
      discussed.

PMID- 16621391
TI  - The cardioprotective effect of uridine and uridine-5'-monophosphate: the role of
      the mitochondrial ATP-dependent potassium channel.
AB  - The activity of mitochondrial ATP-dependent potassium channel (mitoKATP) of rat
      heart and liver mitochondria was shown to decrease during aging. This partially
      explains the increase of risk of ischemia at a mature age since mitoKATP
      activation provides cardioprotection. We demonstrated that uridine-5'-diphosphate
      (UDP) possesses the property to activate mitoKATP. At a concentration of 30
      microM, it reactivated mitoKATP in mitochondria, and 5-hydroxydecanoate (5-HD)
      eliminated this effect. In experimental animals, UDP precursors uridine and
      uridine-5'-monophosphate (UMP) (both 30 mg/kg, administered intravenously 5 min
      before coronary occlusion) decreased the myocardium ischemic alteration index
      (1.9 and 3.5 times, respectively) and the T-wave amplitude within 60 min after
      occlusion. Both effects were inhibited by Glibenclamide (Glib) and 5-HD. UMP and
      uridine decreased the number of premature ventricular beats 5.6 and 1.9 times and
      the duration of ventricular tachycardia 9.4 and 4.1 times, respectively. Glib and
      5-HD inhibited the anti-arrhythmic parameters, 5-HD being less effective. Uridine
      and UMP decreased the duration of fibrillation 10.8 and 3.6 times, respectively,
      and this effect was not abolished by Glib and 5-HD. Thus, uridine and UMP, which
      are the precursors of UDP in the cell, possess cardioprotective properties.
      MitoKATP prevents mainly ischemic injuries and partially rhythm disorders.

PMID- 16621392
TI  - MR-imaging of anterior tibiotalar impingement syndrome: agreement, sensitivity
      and specificity of MR-imaging and indirect MR-arthrography.
AB  - OBJECTIVE: To clarify the role of MR-imaging in the diagnosis of anterior ankle
      impingement syndromes. MATERIALS AND METHODS: We prospectively examined 51
      consecutive patients with chronic ankle pain by MR-imaging. Arthroscopy was
      performed in 29 patients who previously underwent non-enhanced MR-imaging; in 11
      patients, indirect MR-arthrography additionally was performed. MR-examinations
      were correlated with clinical findings; MR and arthroscopy scores were
      statistically compared, agreement was measured. RESULTS: Arthroscopy demonstrated
      granulation tissue in the lateral gutter (38%) and anterior recess (31%), lesions
      of the anterior tibiofibular (31%) and the anterior talofibular ligament (21%) as
      well as intraarticular bodies (10%). Stenosing tenosynovitis and a ganglionic
      cyst were revealed as extraarticular causes for chronic ankle pain by MR
      examination (17%). Agreement of MR-imaging and arthroscopy was fair for the
      anterior talofibular ligament and the anterior joint cavity (kappa 0.40). Major
      discrepancy was found for non-enhanced MR scans (kappa 0.49) when compared with
      indirect MR-arthrography (kappa 0.03) in the anterior cavity. The sensitivity for
      lesions of the anterior talofibular and calcaneofibular ligament and the anterior
      cavity (0.91-0.87) detected by MR-imaging was superior in comparison to lesions
      of the anterior tibiofibular ligament and anteromedial cavity (0.50-0.24).
      CONCLUSION: MR-imaging provides additional information about the mechanics of
      chronic ankle impingement rather than an accurate diagnosis of this clinical
      entity. The method is helpful in differentiating extra- from intra-articular
      causes of ankle impingement. Indirect MR-arthrography has little or no additional
      value in patients with ankle impingement syndrome.

PMID- 16621393
TI  - High-resolution computed tomography findings in elderly patients with asthma.
AB  - OBJECTIVE: Based on the hypothesis that airway remodelling is related to the
      duration of asthma, HRCT scanning should show greater abnormalities in the early
      onset than the late-onset asthmatics. It was, therefore, intended to assess the
      presence and the frequency of airway and parenchymal abnormalities with high
      resolution computed tomography (HRCT) in elderly asthmatic patients, and to
      determine whether these abnormalities are related to the duration of asthma.
      PATIENTS AND METHODS: Sixty-eight clinically stable asthmatic patients aged > or
      =60 yr were included in this prospective study. The patients were separated into
      two groups according to the duration of symptoms as late-onset asthma (n=31) with
      disease duration of <5 yr, and early-onset asthma (n=37) with disease duration of
      > or =5 yr. All patients were lifelong non-smoker and had been using inhaled beta
      agonists and inhaled steroids. HRCT-scanning and histamine inhalation test were
      performed on all patients. RESULTS: In comparison with late-onset asthmatic
      patients, those with early-onset asthma had significantly higher frequency of
      emphysema (21.6% versus 0.0%, p=0.006), bronchial dilatation (13.9% versus 0.0%,
      p=0.03) and bronchial wall thickness (41.7% versus 12.9%, p=0.01). Multiple
      logistic regression analysis identified that early-onset of disease was an
      independent risk factor for the presence of irreversible HRCT-scan abnormalities
      in elderly asthmatics [odds ratio (OR): 9.4 (2.7-32.7), p=0.00001]. CONCLUSION:
      Present data suggest that HRCT abnormalities in early-onset elderly asthmatics
      reflect parenchymal and airway changes that become irreversible throughout the
      long course of the disease.

PMID- 16621394
TI  - Study of severe and rare complications of transarterial chemoembolization (TACE)
      for liver cancer.
AB  - OBJECTIVE: To study severe and rare complications of transarterial
      chemoembolization (TACE) for liver cancer. METHODS: Clinical records of severe
      and rare complications following TACE in 1348 cases of liver cancer from January
      1997 to February 2004 were studied retrospectively. RESULTS: A total of 2012 TACE
      procedures were performed for 1348 patients. There were 3 cases of spontaneous
      rupture of liver cancer, 1 case of perforation of duodenum, 3 cases of liver
      abscess (1 of them was associated with sepsis), 1 case of pulmonary embolism, 1
      case of spasm of the hepatic artery, 40 cases of hepatic artery occlusion, 3
      cases of femoral nerve injury, 1 case of bilioma and 1 case of acute renal
      failure. CONCLUSION: Although the severe complications of TACE are rare, the
      procedure should be done cautiously including super selection of hepatic artery,
      slow infusion of lipiodol, careful postoperative observations and early detection
      and management of complications.

PMID- 16621395
TI  - Multidetector row CT angiography of living related renal donors: is there a need
      for venous phase imaging?
AB  - OBJECTIVE: To prospectively evaluate whether renal venous anatomy can be detected
      from arterial phase images of multidetector row CT (MDCT) of renal donors.
      MATERIAL AND METHODS: Institutional review board approved our study protocol with
      waiver of consent. Forty-eight consecutive renal donors (age range, 21-56 years;
      M:F, 20:28) referred for MDCT evaluation were included. Two sub-specialty
      radiologists performed an independent and separate evaluation of renal venous
      anatomy in arterial and venous phase images. Opacification of renal venous
      structures was scored on a five-point scale (1-not seen; 3-minimal opacification;
      5-excellent opacification). Arterial and venous phase opacification scores were
      compared by Wilcoxon signed rank test. RESULTS: Both readers detected all renal
      venous anomalies in arterial as well as venous phase images. Each reader detected
      accessory right renal veins (n=14), retroaortic left renal vein (n=2),
      circumaortic left renal vein (n=1), and left renal hilar arteriovenous
      malformation (n=1) in arterial phase images. Retroaortic left renal venous branch
      was difficult to differentiate from lumbar vein (reader-1, n=1; reader-2, n=2) in
      both arterial and venous phase images. Sensitivity of detection of renal veins,
      left adrenal, gonadal and lumbar veins in arterial phase images was 100, 83-88,
      100, and 85-90%, respectively. As expected, venous phase images showed
      significantly greater opacification of renal veins, left gonadal, adrenal and
      lumbar veins (p<.05). However, this did not substantially limit the evaluation of
      renal venous anatomy in arterial phase images. Both readers had substantial
      interobserver agreement (kappa coefficient, 0.7; p<0.05). CONCLUSIONS: Arterial
      phase MDCT images alone can be used to detect renal venous anomalies, and to
      identify small left renal venous branches namely, the left gonadal, adrenal and
      lumbar veins in renal donors. Venous phase MDCT acquisition is not necessary for
      evaluation of renal venous anatomy in renal donors.

PMID- 16621396
TI  - Indirect magnetic resonance lymphangiography in patients with lymphedema
      preliminary results in humans.
AB  - PURPOSE: To assess the feasibility of indirect magnetic resonance (MR)
      lymphangiography with intracutaneous injection of gadodiamide, a commercially
      available, non-ionic, extracellular paramagnetic contrast agent for the detection
      of lymphatic vessels in patients with lymphedema. MATERIALS AND METHODS: In 2005,
      three patients with lymphedema of the lower extremities (1 primary, 2 secondary)
      were referred by the Foeldi Clinic for Lymphology for indirect magnetic resonance
      lymphangiography. 4.5 mL of gadodiamide and 0.5 mL of mepivacainhydrochloride 1%
      were injected intracutaneously into the dorsal aspect of each foot. MR imaging
      was performed with a 1.5-T system equipped with high-performance gradients. For
      indirect magnetic resonance lymphangiography, a 3D Fast Low Angle Shot (FLASH)
      sequence (TR/TE: 5.1/1.23; flip angle: 25; matrix: 448 x 448; bandwidth: 330
      Hz/pixel; 6/8 rectangular field of view with a maximum dimension of 500 mm;
      slices: 88; voxel size: 2.0 mm x 1.0 mm x 1.0mm; acquisition time: 0 min 31 s)
      was used. RESULTS: Indirect magnetic resonance lymphangiography depicted
      lymphatic vessels of the lower and upper leg, and inguinal lymph nodes in all
      three patients. After 5 min of contrast material application, concomitant venous
      enhancement was detected. Collateral vessels with dermal back-flow were seen in
      two patients. A lymphocele in the inguinal region with the afferent lymphatic
      vessel was depicted in one patient. CONCLUSION: In the presented small study
      group, indirect magnetic resonance lymphangiography was technically feasible, and
      no complications were observed after intracutaneous injection of gadodiamide.
      Visualizing the lymphatic vessels and accompanying complications non-invasively
      and without the use of radiation, the presented method has the capability to
      become a routine diagnostic imaging tool in patients with primary and secondary
      lymphedema. The method is not able to characterize lymph node morphology, but
      could provide additional information about the lymphatic vessels when lymph nodes
      are examined, e.g. with super-paramagnetic iron oxide particles.

PMID- 16621397
TI  - Enhancement effects of test injection with a small amount of MR contrast medium
      in the oral and maxillofacial region.
AB  - PURPOSE: To examine whether the signal intensity of dynamic contrast-enhanced MRI
      (DCE-MRI) is altered by test injection of 1 ml of contrast medium, and if so,
      whether this change affects the DCE-MRI analysis. MATERIALS AND METHODS: Six
      healthy volunteers were examined by DCE-MRI using a Magnevist syringe and/or an
      Omniscan syringe for the injection of contrast medium. Each scan was performed 10
      times using steady-state free precession (3D-FISP), a sequence for DCE-MRI,
      before and after intravenous injection of 1 ml of the contrast medium. The
      internal pterygoid muscle, masseter muscle, tongue, parotid gland, submandibular
      gland, bone marrow of the mandible, subcutaneous adipose tissue, and common
      carotid artery were determined to be regions of interest (ROI), and the ROI
      internal average signal intensity was measured. The 10 data sets obtained before
      or after contrast medium administration for each ROI were evaluated using the
      paired t-test. RESULTS: The test injection increased the signal intensities of
      six of eight ROIs, with all 20 experiments in the submandibular gland showing
      significant differences. There was no significant difference in the two ROIs
      corresponding to the carotid artery and subcutaneous adipose tissue of the cheek.
      CONCLUSIONS: The enhanced signal intensity in the tissue might have been caused
      by the small amount of contrast medium in the test injection. To eliminate this
      discrepancy caused by the test injection, a pre-contrast scan should be performed
      when the average signal intensity of an ROI is measured. We therefore believe
      that the data obtained before a test injection may be important in the analysis
      of DCE-MRI.

PMID- 16621398
TI  - Membranous duodenal stenosis: initial experience with balloon dilatation in four
      children.
AB  - INTRODUCTION: We present a novel approach to the treatment of membranous duodenal
      stenosis (MDS). To our knowledge this is the first paper to describe balloon
      dilatation for this entity. MATERIAL AND METHODS: Four children, 2 boys and 2
      girls, aged between 8 and 28 days, underwent duodenal balloon dilatation. Balloon
      dilatation was performed under general anaesthesia using standard angiography
      balloons per os. Balloon diameters ranged from 6 to 14 mm. RESULTS: All balloon
      dilatations were successful. None of the procedures showed procedural or post
      procedural complications. None of the patients subsequently required surgical
      intervention. To date all children are doing well. DISCUSSION: The initial
      experience with balloon dilation of MDS showed a 100% success rate, without
      procedural or post-procedural complications. The results obtained in this small
      group of patients suggest that the use of balloon dilatation in cases of MDS may
      be a safe technique that can be readily performed by an experienced
      interventional radiologist.

PMID- 16621400
TI  - Subspecies-specific distribution of intervening sequences in the Bacillus
      subtilis prophage ribonucleotide reductase genes.
AB  - A collection of 212 gram-positive bacilli isolated from natural habitats was
      screened for the presence of intervening sequences (introns and intein-coding
      sequences) in the SPbeta prophage-related ribonucleotide reductase genes bnrdE
      and bnrdF. Three novel configurations were identified on the basis of the
      presence of (i) intervening sequences in bnrdE and bnrdF, and (ii) an ORF in the
      bnrdE-bnrdF spacer. Analysis of the cell wall genetic determinants as well as of
      the incorporation of radio-labelled glycerol into cell wall allowed newly and
      previously identified B. subtilis strains with different configurations of
      bnrdE/bnrdF intervening sequences to be assigned to one of two subspecies.
      Strains apparently belonging to the subsp. subtilis contain three intervening
      sequences many of which are associated with the putative homing endonuclease
      activity. Strains of the subsp. spizizenii contain only one or two ORF-less group
      I introns. Introns occupying bnrdF are confined to the subspecies subtilis.

PMID- 16621401
TI  - Halomonas alkaliantarctica sp. nov., isolated from saline lake Cape Russell in
      Antarctica, an alkalophilic moderately halophilic, exopolysaccharide-producing
      bacterium.
AB  - The taxomony of strain CRSS (DSM 15686(T)=ATCC BAA-848(T)) isolated from Cape
      Russell in Antarctica (Ross Sea, 74 52.35 S 163 53.03 E) was investigated in a
      polyphasic approach. The morphological, physiological and genetic characteristics
      were compared with that of related species of the genus Halomonas. The isolate
      grew optimally at pH 9.0, 10% NaCl at 30 degrees C. The cells were Gram-negative
      aerobic rods able to produce exopolysaccharide. They accumulated glycine-betaine,
      as a major osmolyte, with minor components ectoine and glutamate. The strain CRSS
      biosynthetised alpha-glucosidase. The polar lipid profile consisted of
      phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol as
      major components. Ubiquinone with nine repetitive unities (Q9) was the only
      quinone found and the fatty acid composition was dominated by C18:1 (53%). The
      G+C content of DNA was 55.0mol% and its phylogenetic position was established by
      16S rRNA gene sequencing as a member of the genus Halomonas. For physiological,
      chemotaxonomic and genetic features (DNA-DNA hybridisation) it is proposed to
      classify the isolate as a new species for which we propose the name Halomonas
      alkaliantarctica sp. nov.

PMID- 16621402
TI  - Molecular typing of wine yeast strains Saccharomyces bayanus var. uvarum using
      microsatellite markers.
AB  - The Saccharomyces bayanus var. uvarum yeasts are associated with spontaneous
      fermentation of must. Some strains were shown to be enological yeasts of interest
      in different winemaking processes. The molecular typing of S. bayanus var. uvarum
      at the strain level has become significant for wine microbiologists. Four
      microsatellite loci were defined from the exploration of genomic DNA sequence of
      S. bayanus var. uvarum. The 40 strains studied were homozygote for the locus
      considered. The discriminating capacity of the microsatellite method was found to
      be equal to that of karyotypes analysis. Links between 37 indigenous strains with
      the same geographic origin could be established through the analysis of
      microsatellite patterns. The analysis of microsatellite polymorphism is a
      reliable method for wine S. bayanus var. uvarum strains and their hybrids with
      Saccharomyces cerevisiae identification in taxonomic, ecological studies and
      winemaking applications.

PMID- 16621403
TI  - Advances in the analysis of phenolic compounds in products derived from bees.
AB  - Honey and propolis are rich in phenolic compounds, which act as natural
      antioxidants, and are becoming increasingly popular because of their potential
      role in contributing to human health. These compounds can also be used as
      indicators in studies into the floral and geographical origin of the honey and
      propolis themselves. We present here an overview of current analytical methods
      for measuring polyphenols in honey and propolis. The analytical procedure to
      determine individual phenolic compounds involves their extraction from the
      sample, analytical separation and quantification. The techniques reviewed are
      based on spectrophotometry as well as analytical separation techniques such as
      gas chromatography, high-pressure liquid chromatography and capillary
      electrophoresis.

PMID- 16621404
TI  - Qualitative identification of tea categories by near infrared spectroscopy and
      support vector machine.
AB  - Near-infrared (NIR) spectroscopy has been successfully utilized for the rapid
      identification of green, black and Oolong tea. The spectral features of each tea
      category are reasonably differentiated in the NIR region, and the spectral
      differences provided enough qualitative spectral information for the
      identification of tea. Support vector machine (SVM) as the pattern recognition
      was applied to identify three tea categories in this study. The top five
      principal components (PCs) were extracted as the input of SVM classifiers by
      principal component analysis (PCA). The RBF SVM classifiers and the polynomial
      SVM classifiers were studied comparatively in this experiment. The best
      experimental results were obtained using the radial basis function (RBF) SVM
      classifier with sigma=0.5. The accuracies of identification were all more than
      90% for three tea categories. Finally, compared with the back propagation
      artificial neural network (BP-ANN) approach, SVM algorithm showed its excellent
      generalization for identification results. The overall results show that NIR
      spectroscopy combined with SVM can be efficiently utilized for rapid and simple
      identification of the tea categories.

PMID- 16621405
TI  - Quantitative analysis of liquid formulations using FT-Raman spectroscopy and HPLC
      The case of diphenhydramine hydrochloride in Benadryl.
AB  - The capability of FT-Raman spectroscopy for the fast and non-destructive
      quantitative analysis of liquid formulations was tested and the results were
      compared to those obtained by HPLC. Diphenhydramine hydrochloride (DPH), the
      active ingredient of Benadryl, was determined in the presence of the numerous
      excipients of the elixir. A Raman calibration model was developed by measuring
      the peak intensities of different standard solutions of DPH vibration at 1003 cm(
      1). Application of the calibration model on the peak intensity recorded from the
      as-received commercially available sample with 2.5 mg ml(-1) DPH nominal value
      yielded a value of 2.49+/-0.05 mg ml(-1) DPH. The reliability of this method was
      verified by testing it against the conventionally used HPLC. The results from
      both methods were in excellent agreement. The main advantage of Raman over HPLC
      method during routine analysis is that is considerably faster and less solvent
      consuming. Furthermore, Raman spectroscopy is non-destructive for the sample. On
      the other hand, the detection limit for Raman spectroscopy is much higher than
      the corresponding for the HPLC methodology.

PMID- 16621406
TI  - Applying biofluid 1H NMR-based metabonomic techniques to distinguish between HIV
      1 positive/AIDS patients on antiretroviral treatment and HIV-1 negative
      individuals.
AB  - Metabonomics, the study of metabolites and their role in various physiological
      states, is a novel methodology arising from the post-genomics era and has
      extensive biomedical application. This technology has exhibited vast success in
      the identification and study of human diseases and may find further application
      in the study of HIV/AIDS. Specifically, the wide range of clinical and metabolic
      abnormalities associated with the use of antiretroviral (ARV) treatment may be
      investigated. To this end, this preliminary study evaluated whether metabonomic
      techniques could distinguish between HIV-1 positive/AIDS patients utilizing
      antiretroviral therapy and HIV-1 negative individuals. Serum metabolic profiles
      determined by 1H nuclear magnetic resonance (NMR) spectroscopy combined with
      pattern recognition analysis of the data showed that this distinction was
      attainable; suggesting that ARV-associated side-effects could be monitored
      utilizing NMR metabonomic techniques.

PMID- 16621407
TI  - Quality evaluation of Platycladus orientalis (L.) Franco through simultaneous
      determination of four bioactive flavonoids by high-performance liquid
      chromatography.
AB  - Platycladus orientalis (L.) Franco (Cupressaceae), a traditional Chinese herb and
      food additive, has been used for treatments of gout, rheumatism, diarrhoea and
      chronic tracheitis. To evaluate the quality of P. orientalis (L.) Franco, a
      sensitive, simple and accurate reversed-phase high-performance liquid
      chromatographic (RP-HPLC) separation method with a photodiode array detector
      (DAD) was developed for the determination of four main bioactive flavonoids,
      rutin, quercitrin, quercetin and amentoflavone. Separation of the four compounds
      was achieved by the HPLC assay (Agilent Eclipse XDB-C 18 column with mobile
      phase, methanol-acetonitrile-18 mM sodium acetate buffer (pH 3.5) and recorded at
      UV 356 nm). This method showed good linear relation in the range of 0.8-80
      microg/ml for rutin, 1.84-184 microg/ml for quercitrin, 0.72-72 microg/ml for
      quercetin and 0.72-72 microg/ml for amentoflavone. The correlation coefficients
      of the calibration curve for the analysis were all higher than 0.999. In
      addition, the contents of those four flavonoids in P. orientalis (L.) Franco
      growing in 12 different locations in China were compared to establish the
      effectiveness of the method.

PMID- 16621408
TI  - RP-HPLC determination of paraoxonase 3 activity in human blood serum.
AB  - The aim of the present work was to establish conditions for paraoxonase 3 (PON3)
      activity determination in human blood serum with simvastatin (SV) as a substrate.
      The activity of PON3 is considered as a good early predictor of susceptibility to
      premature atherosclerosis as well as of statin therapy effectiveness. The method
      used quantifies the SV and beta,delta-dihydroxyacid simvastatin (SVA) liberated
      from SV after incubation with blood serum, followed by deproteinization of the
      reaction mixture. Separation of SV and SVA was performed on an LC(18) column by
      isocratic elution with acetonitrile-K-phosphate buffer of pH 4.5 (v/v, 70:30) as
      a mobile phase at flow rate of 1.5 ml min(-1). Detection based on ultraviolet
      absorption at a wavelength of 239 nm was reliable for the simultaneous assay of
      SV and SVA. The applied method was sufficiently sensitive, precise and accurate
      for determination of low simvastatin lactone hydrolase (statinase) activity in
      blood serum of children (1.97-6.86 pmol min(-1) ml(-1)). The method is
      characterized by good linearity over the measurement range of 0.5-6 microg ml(-1)
      (1.194-14.3 nmol ml(-1)). Limits of detection (LOD) and quantitation (LOQ) for SV
      were 3.1 and 10.4 ng ml(-1), respectively. In case of SVA, LOD and LOQ were 4.7
      and 14.44 ng ml(-) for a 20 microl sample, respectively. Precision and accuracy
      of PON3 statinase activity determination in human blood serum with SV as
      substrate were satisfactory and acceptable for bioanalytical methods.

PMID- 16621409
TI  - Development of a rapid multi-element method of analysis of antitussive syrups by
      inductively coupled plasma atomic emission spectrometry and direct sample
      introduction.
AB  - A new rapid method was developed and optimized for routine multi-element
      determination of traces of metals in antitussive syrups using direct introduction
      of diluted syrup into the nebulization system of inductively coupled plasma
      atomic emission spectrometer (ICP-AES). Using a Scott-type double-pass spray
      chamber combined with a cross-flow nebulizer, the optimum ICP conditions, like RF
      incident power, argon gas flow rate and nebulizer sample uptake flow rate were
      found. A critical objective of the study was to evaluate the matrix effect on the
      intensity and consequently on the sensitivity of the developed method. Thus, the
      maximum syrup concentration which could be introduced into the argon plasma, was
      estimated. The sensitivity variation was calculated as compared to the
      corresponding sensitivity obtained from aqueous solutions for each analyte. The
      performance characteristics of the proposed method were evaluated for
      quantitative and semi-quantitative determination and finally, the method was
      applied to the analysis of various commercial antitussives.

PMID- 16621410
TI  - Analysis of phytosterols in foods.
AB  - Phytosterols are bioactive compounds, one of their most studied and outstanding
      properties being their cholesterol-lowering activity. This explains the growing
      interest in the phytosterol contents of foods as either intrinsic or added
      components. The different steps (extraction, saponification, clean up,
      chromatographic determination) of plant sterol determination are reviewed, and
      emphasis is placed on the methods used to assay different phytosterols in food.

PMID- 16621411
TI  - A quality evaluation strategy for multi-sourced active pharmaceutical ingredient
      (API) starting materials.
AB  - Establishing appropriate impurity specifications for active pharmaceutical
      ingredient (API) starting materials is an important component of the
      commercialization and registration of an API. Multiple sources and routes of
      manufacture of starting materials and the capability of the API synthetic process
      for tolerating impurities introduced with starting materials must be understood.
      A strategy for purity method development and use test evaluation of starting
      materials to aid in establishing quality requirements is described. Phenyl methyl
      amino propanol (PMAP), a starting material that may be used for fluoxetine
      hydrochloride and atomoxetine hydrochloride, is used to illustrate the quality
      evaluation strategy. Knowledge of actual and potential synthetic routes was used
      to predict potential impurities and guide purity method development. Multiple
      analytical methods that were semi-orthogonal in the nature of impurity retention
      (ion-pairing, ion interaction and hydrophilic interaction chromatographic modes)
      along with use tests were investigated.

PMID- 16621412
TI  - Study of the interaction between rifapentine and isoniazid under acid conditions.
AB  - A well-known problem of anti-tuberculosis fixed-dose combination (FDC) products
      containing rifampicin (R) and isoniazid (H) is the fall in bioavailability, in
      particular of R, when two or more drugs are present together. The same has been
      ascribed to hydrolysis of R to 3-formylrifamycin (3-RIF) under stomach acid
      conditions and reaction of the latter with H to form isonicotinyl hydrazone
      (HYD). The objective of present study was to explore whether the same reaction
      occurred when H was present along with rifapentine (Rp), a newer long acting
      rifamycin, which is structurally similar to R. Clinical trials are currently
      undergoing for co-administration of Rp with H in patients who had completed 2
      months of standard chemotherapy. For the purpose, first a validated HPLC method
      was developed for the separation of Rp and H, and the same was used for the study
      of interaction between the two drugs. Like R, Rp was also found to convert to 3
      RIF in acid conditions, which reacted further with H to form HYD. The pH-rate
      profile was also similar in shape to that established with the combination of R
      and H; maximum decomposition occurred at pH 2, where Rp loss was to an extent of
      approximately 30%, while corresponding decomposition of H was approximately 9%.
      These values were similar to those reported for the combination of R
      (approximately 33%) and H (approximately 10%). Hence, the study suggests that co
      administration of Rp and H should be avoided, like in case of R and H, and the
      two drugs should not be formulated directly into a single dosage form.

PMID- 16621413
TI  - Improving method capability of a drug substance HPLC assay.
AB  - The assay of a drug substance (DS) is one of the tests required to confirm the
      active pharmaceutical ingredient (API) quality at release. In the past, usually
      volumetric titration methods were performed, that were precise, but often non
      specific. Nowadays specific chromatographic assay procedures are preferred.
      However, high performance liquid chromatographic (HPLC) methods, the way they are
      usually executed, tend to be less precise and have a larger total method
      variation compared to titration methods. The capabilities of fully validated
      titration and HPLC assay methods were determined and compared. It was studied
      which factors had the largest effects on the capability of chromatographic HPLC
      methods in order to improve their precision and precision-to-tolerance ratio.
      This was done using multiple Gage R&R (repeatability & reproducibility) studies
      and an experimental design approach. The investigations showed that it was
      feasible to define an HPLC method with a similar capability as the titration
      method. The most important factor determining the precision was demonstrated to
      be higher sample and reference material weights. When low weights are to be used,
      increasing the number of sample preparations and the number of reference
      solutions may enhance the method capability.

PMID- 16621414
TI  - Monitoring eicosanoid biosynthesis via lipoxygenase and cyclooxygenase pathways
      in human whole blood by single HPLC run.
AB  - Eicosanoids play an important role as lipid mediators for physiological and
      pathological processes. Inhibitors of their biosynthesis have been developed as
      drugs for various diseases with major health political relevance. The search for
      more efficient inhibitors of eicosanoid formation requires simultaneous
      monitoring of various metabolic pathways. We developed an HPLC-based assay
      system, which quantifies lipoxygenase metabolites leukotriene B4 (LTB4), 5
      hydroxyeicosatetraenoic acid (5-HETE), 12-hydroxyeicosatetraenoic acid (12-HETE),
      15-hydroxyeicosatetraenoic acid (15-HETE) and cyclooxygenase metabolite 12
      hydroxy-5,8,10-heptadecatrienoic acid (12-HHT) in whole human blood. Eicosanoid
      formation in blood is initiated with calcium ionophore A23187, arachidonic acid
      and calcium and magnesium ions. After solid phase extraction the different
      eicosanoids were separated by isocratic RP-HPLC using prostaglandin B1 as
      authentic standard. To verify the assay we determined the IC50 of known
      inhibitors of eicosanoid biosynthesis (zileuton, indomethacin,
      nordihydroguaiaretic acid). The test system is simple. It does not require
      extensive methodological experience and can be carried out in any biochemical
      laboratory. The analytical procedure can be robotized and thus, the assay appears
      suitable for medium-throughput testing of drugs.

PMID- 16621415
TI  - Development of an enzyme-linked immunosorbent assay for fentanyl and applications
      of fentanyl antibody-coated nanoparticles for sample preparation.
AB  - A sensitive enzyme-linked immunosorbent assay (ELISA) was developed for the
      detection of fentanyl in serum and urine. The ELISA used an indirect competitive
      method produced by coating the plate with thyroglobulin conjugated with fentanyl
      hapten. Antibodies against fentanyl-hemocyanin were detected by a goat-anti
      rabbit antibody conjugated with alkaline phosphatase. Calibration standard curves
      ranged from 0.5ng/ml to 50mug/ml (IC(50)=10ng/ml), and the limits of detection
      were 0.5 and 1.0ng/ml for serum and urine, respectively. The intra- and inter
      assay variations were less than 8% and 10%, respectively. The antibody produced
      against fentanyl completely cross-reacted with p-fluorofentanyl, thienylfentanyl
      and 3-methylthienylfentanyl, cross-reacted highly with carfentanil (85%), but was
      considered non-cross-reactive with alpha-methylfentanyl (5%), sufentanil (<1%),
      alfentanil (<1%) and lofentanil (<1%). Nano-sized iron oxide magnetic particles
      coated with the developed fentanyl antibody were capable of specific binding and
      releasing of fentanyl from urine samples. This enabled the drug to be effectively
      pre-concentrated and decreased the limit of detection by approximately one order
      of magnitude. The analytical background noise was significantly reduced to enable
      fentanyl detection at concentrations originally below chromatographic limit of
      detection. The change of platform for antibody binding with nanoparticles
      demonstrated a novel use of antibodies for sample preparation and should
      facilitate drug screening by traditional ELISA.

PMID- 16621416
TI  - Identification of novel saponins from edible seeds of Japanese horse chestnut
      (Aesculus turbinata Blume) after treatment with wooden ashes and their
      nutraceutical activity.
AB  - Natural seeds of Japanese horse chestnut (Aesculus turbinata Blume) contain large
      amounts of mixed triterpenoidal saponins called escins. Recent studies have shown
      that escins have several biological activities including anti-inflammatory action
      and inhibitory effects on the absorption of ethanol and glucose. For the edible
      utilization of the seeds, natural seeds are usually treated with wooden ashes to
      remove harshness. Here, we found the novel compounds derived from escins in the
      edible seeds after the food processing with wooden ashes. The instrumental
      analyses revealed the chemical structures of escins and the derivatives. These
      compounds are identified as four types of deacetylescins Ia, IIa, Ib, and IIb as
      well as two types of desacylescins I and II. To determine their biological
      activity, the purified compounds were tested for their potential nutraceutical
      activity. The oral glucose tolerance test in mice revealed that a single oral
      administration of the isolated components of deacetylescins at a dose of 100
      mg/kg was clearly effective in attenuating the elevation of blood glucose levels.
      The inhibitory effects of escins and their derivatives were in the order of
      escins>deacetylescins>desacylescins. Moreover, we found the inhibitory activity
      of those compounds on pancreatic lipase. Escins were the most potent in
      inhibiting the enzyme activity, and followed by desacylescins and then
      deacetylescins. Taken together, our results suggest the potential usefulness of
      novel saponins including deacetylescins and desacylescins from edible seeds as
      novel sources for nutraceutical foods with anti-obese effects.

PMID- 16621417
TI  - Flow and sequential injection methods for the spectrofluorimetric determination
      of aluminium in pharmaceutical products using chromotropic acid as chromogenic
      reagent.
AB  - This work reports rapid and sensitive FI and SI spectrofluorimetric methods for
      the determination of aluminium in pharmaceutical formulations. The methods are
      based on the reaction of aluminium with chromotropic acid (CA) in acidic medium
      to form a water-soluble complex (lambdaex.=360 nm, lambdaem.=385 nm). The
      proposed methods were validated in terms of linearity, repeatability, detection
      limit, accuracy and selectivity. The calibration curves were linear over the
      range of 0.03-2.0 and 0.1-4.0mg/l of aluminium using the FI and SI assays,
      respectively. The repeatabilities (sr=0.8% and 1.1% at 1mg/l aluminium using the
      FI and the SI assay, respectively, n=12) were satisfactory. The FI and SI methods
      proved to be adequately selective and sensitive with respective 3sigma limits of
      detection equal to cL=0.01 and 0.03 mg/l Al(III). The sampling rates were 120 and
      72 h(-1) with the FI and SI assay. The methods were applied successfully to the
      analysis of pharmaceutical formulations (tablets and suspensions). The results
      were in good agreement with those by an official reference method and the nominal
      values of the pharmaceutical products.

PMID- 16621418
TI  - Physicochemical characterization of meloxicam-mannitol binary systems.
AB  - The dissolution behaviour of drugs remains one of the most challenging aspects in
      formulation development. The anti-inflammatory drug, meloxicam (ME) has poor
      water solubility. The object of this experiment was to improve the rate of
      dissolution of meloxicam in capsule form. In order to achieve this, mannitol was
      used as a carrier in different ratios, in physical mixtures and melted forms.
      Mannitol, a sugar alcohol, is a cheap and readily available excipient.
      Differential scanning calorimetry (DSC) and X-ray diffractometry were used to
      investigate the characteristics of meloxicam-mannitol binary systems.
      Multivariate curve resolution (MCR) as a chemometric method was applied to
      interpret the X-ray diffractograms. This is believed to be the first published
      use of this reasoning for this interpretation. According to the results, the
      amount of mannitol and the particle size of ME were important factors in the rate
      of dissolution. To the perfect dissolution of ME, the melt technology was used
      which resulted in mixed crystals. This technology was made by 10 parts of
      mannitol and 1 part of ME2 with about 6 microm in average particle size. The
      interaction (adhesion) between mannitol and ME for physical mixtures was not
      enough to the perfect dissolution.

PMID- 16621419
TI  - Near infrared spectroscopy and process analytical technology to master the
      process of busulfan paediatric capsules in a university hospital.
AB  - The prescription of unlicensed oral medicines in paediatrics leads the hospital
      pharmacists to compound hard capsules, such as busulfan, an alkylating agent
      prescribed in preparative regimens for bone marrow transplantation. In this
      study, we have investigated how the general principle of process analytical
      technology (PAT) can be implemented at the small size of our hospital pharmacy
      manufacturing unit. Near infrared spectroscopy (NIRS) was calibrated for raw
      material identification, blend uniformity analysis and final content uniformity
      of busulfan hard capsules of 11 different strengths. Measurements were performed
      on capsules from 2 to 40 mg (n=440). After optimisation, accuracy and linearity
      of the NIRS quantitative method was demonstrated after comparison with a
      previously validated quantitative high performance thin layer chromatography
      (HPTLC) method. Such a comparison led to attractive NIRS precision: +/-0.7 to +/
      1.0 mg for capsules from 2 to 40 mg, respectively. As NIRS is a rapid and non
      destructive technique, the individual control of a whole batch of busulfan
      paediatric capsules intended to be administrated is possible. Actually, mastering
      the process of busulfan paediatric capsules with the NIRS integrated into the
      notion of PAT is a powerful analytical tool to assess the process quality and to
      perform content uniformity of at least 5mg busulfan-containing capsules.

PMID- 16621420
TI  - Caffeine modulates potassium currents in Drosophila neurons.
AB  - We investigated the effects of caffeine on the delayed-rectifier potassium
      current (IK(DR)) which is important in repolarizing the membrane potential, and
      the transient A-type potassium current (IK(A)) which regulates neuronal firing
      threshold and the rate of repetitive action potentials. The whole-cell patch
      clamp technique was used to measure the currents from cultured Drosophila neurons
      derived from embryonic neuroblasts. The currents were measured from neurons
      before and after the application of 1mM caffeine to the external saline of the
      same neuron. IK(DR) measured in the caffeine-containing solution (470+/-36 pA,
      n=18), was smaller than that measured in the control 6K/0Ca Tris solution (745+/
      51 pA, n=18). IK(A) measured in the caffeine-containing solution (17+/-2 pA,
      n=16) was smaller than that measured in the control 6K/0Ca Tris solution (35+/-4
      pA, n=16). These results indicate that caffeine reduces IK(DR) and IK(A)
      amplitudes and possibly leads to increased action potential frequency and
      enhanced neuronal excitability.

PMID- 16621421
TI  - Diabetes, poverty, and Latin America.

PMID- 16621422
TI  - Follicle-stimulating hormone (FSH) stimulates the expression of Pin1, a peptidyl
      prolyl isomerase, in the bovine granulosa cells.
AB  - A peptidyl-prolyl isomerase, Pin 1, has been shown to play a role in the
      regulation of cell cycle progression, both in vitro and in vivo. However, the
      involvement of Pin 1 during follicular development is not well understood. The
      aim of this study was first to investigate the expression of Pin 1 mRNA in the
      granulosa and theca cells of the follicle at different developmental stages of
      follicles in the bovine ovary, and second, to examine the effects of follicle
      stimulating hormone (FSH) and estradiol (E2) on the expression of Pin 1 in the
      cultured bovine granulosa cells. Follicles were classified into four groups based
      on the diameter (dominant follicles >8.5mm in diameter, subordinate follicles
      <8.5mm in diameter) and the relative levels of E2 and progesterone (P4) (E2:P4>1,
      estrogen active; E2:P4<1, estrogen inactive): i.e. preovulatory dominant
      follicles (POFs); E2 active dominant follicles (EADs); E2 inactive dominant
      follicles (EIDs); small follicles (SFs). The expression of the Pin 1 gene was
      significantly increased in the granulosa cells of EADs as compared with those of
      other follicles, whereas its expression in theca cells did not differ among
      follicles at different developmental stages. The concentration of 5 ng/ml FSH
      alone and the combination of 1 ng/ml E2 and 5 ng/ml FSH stimulated the expression
      of the Pin 1 gene in bovine granulosa cells. Our data provide the first evidence
      that Pin 1 expression in the granulosa cells but not the theca cells changes
      during follicular development, and that FSH stimulate the expression of the Pin 1
      gene. These results suggest that Pin 1 regulates the timing of cell proliferation
      and may act as an intracellular signal responder in the granulosa cells during
      bovine follicle development.

PMID- 16621423
TI  - The role of sentinel lymph node biopsy in patients with differentiated thyroid
      carcinoma.
AB  - AIM: To evaluate the "state of art" of clinical role of sentinel lymph node (SLN)
      biopsy procedure in patients affected by differentiated thyroid carcinoma.
      METHODS: All papers cited on PubMed/MEDLINE until June 2005, published in
      English, and referred to the key words "sentinel lymph node biopsy" AND "thyroid
      carcinoma" OR "thyroid cancer" were reviewed for the purpose of the present
      study. RESULTS: The first method used for SLN biopsy in thyroid carcinoma
      patients was the vital blue dye technique. This technique had some disadvantages
      as: (a) risk of disruption of the lymphatic channels deriving from the thyroid
      cancer; (b) difficulty in disclosing SLN lying outside the central compartment;
      (c) parathyroid glands can take up blue dye and, thus, can be misinterpreted as
      lymph nodes. Some of the above cited disadvantages were overcome by using the
      lymphoscintigraphy and intraoperative gamma probe technique. A combination of the
      blue dye and gamma probe technique has also been proposed with synergic results.
      CONCLUSION: The reported advantages of the SLN biopsy in small differentiated
      thyroid carcinoma patients can be resumed as follows: (a) better selection of
      patients who would benefit from compartment oriented nodal dissection; (b) more
      accurate lymph node staging; (c) better selection of patients who can require
      (131)I treatment after surgery (SLN positive for metastasis); (d) better
      identification of SLN located out of the central compartment.

PMID- 16621424
TI  - Analysis of risk factors for skip lymphatic metastasis and their prognostic value
      in operated N2 non-small-cell lung carcinoma.
AB  - BACKGROUND: The aim of this study is to report a series and to analyze risk
      factors for skip lymphatic metastasis an their prognostic value in operated N2
      non-small-cell lung carcinoma. METHODS: From 1997 to 2002, 142 patients
      classified pN2 were included in the study. Tumours were classified according to
      the TNM classification. Skips metastases were defined by the cases of N2 disease
      without lobar and interlobar and hilar lymph node involvement. A skip (+) and a
      skip (-) group were defined. Characteristics of tumours, ganglionar involvement
      and survival were analysed in both groups. RESULTS: Forty-two patients fulfilled
      the criteria for skip metastasis. The average number of mediastinal lymph nodes
      resected by patient was similar in both groups, whereas more intrapulmonary nodes
      were dissected in the skip (-) group (4.7 +/- 3 vs 3 +/- 3; p < 0.002). The ratio
      of involved to resected lymph nodes was 0.47 +/- 0.27 in the skip (-) group vs
      0.23 +/- 0.20 in the skip (+) group (p < 0.0001). In the skip (+) group, 85% of
      the patients presenting with a right upper lobe tumour had involvement of the
      superior mediastinal lymph nodes against 40% in the skip (-) group. The 5-year
      survival rate was 48% in the skip (-) group vs 37% in the skip (+) group (p =
      0.49). In multivariate analysis, incomplete resection, tumour size, extended
      resection and pT were significant prognostic factors. CONCLUSIONS: Skip
      metastasis are frequent in non-small-cell lung cancer and complete dissection of
      hilar and mediastinal lymph nodes should remain the surgical standard procedure
      for this disease. However, skip metastasis are not an independent prognostic
      factor in survival.

PMID- 16621425
TI  - Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy
      in advanced/recurrent ovarian cancer patients: The experience of National Cancer
      Institute of Milan.
AB  - AIMS: We report the effects of cytoreductive surgery (CRS) and intraperitoneal
      hyperthermic perfusion (IPHP) in the treatment of advanced/recurrent epithelial
      ovarian cancer (EOC) on survival, morbidity and mortality. PATIENTS: Forty EOC
      patients were studied. Median age was 52.5 years (range: 30-68) and median follow
      up 26.1 months (range: 0.3-117.6). Most patients presented advanced disease
      (stage III/IV). Previous systemic chemotherapy included cisplatin-based, taxol
      based or taxol/platinum containing regimens. RESULTS: After the CRS, 33 patients
      presented no macroscopic residual disease. Five-year overall survival was 15%;
      the mean overall and progression-free survivals were 41.4 and 23.9 months,
      respectively. The morbidity, toxicity and mortality rates were 5%, 15% and 0%,
      respectively. CONCLUSION: Our results suggest that CRS + IPHP merits further
      evaluation by a formal prospective trial.

PMID- 16621426
TI  - The natural history, gross pathology, and histopathology of appendiceal
      epithelial neoplasms.
AB  - AIM: To report the pathology of appendiceal epithelial neoplasms a review of the
      Washington Cancer Institute experience and a PubMed literature search was
      performed. FINDINGS: Epithelial appendiceal neoplasms present a significant
      oncologic challenge. The clinical and pathologic features are unusually varied as
      compared to other gastrointestinal cancers and require expert clinical judgment
      for proper management. CONCLUSIONS: Appendiceal epithelial neoplasms should be
      regarded as a distinct clinical entity with special clinical treatments used for
      optimal management.

PMID- 16621427
TI  - The influence of radioisotope vehicle on breast sentinel node detection.
AB  - AIM: To assess the relationship between carrier molecule size and time elapsing
      between marker injection and sentinel node(s) biopsy in patients with breast
      cancer. MATERIAL: The study performed on 122 women, in whom the sentinel node(s)
      was identified according to the procedure described below. In Group I (n=72
      patients), SN identification was done with radioisotope marker of 400-3000 nm
      molecule size (tin colloid). In Group II (n=50 patients) radioisotope marker of
      <100 nm molecule size (colloidal albumin) was used. METHODS: All the patients of
      both groups received the markers with a single-point, intradermal, periareolar
      injection. Four hours after the injection (Group I - surgery in the next day) or
      immediately before the surgery (in this same day) (Group II), stationary
      lymphoscintigraphy was performed. RESULTS: Mean numbers of sentinel nodes
      identified with the radioisotope method in Groups I and II were 1.22 and 1.48,
      respectively. The difference was statistically significant (p<0.01). CONCLUSIONS:
      There is a relationship between the radioisotope marker molecule size and the
      injection-to-intra-operative evaluation time. Administration of small molecule
      size radioisotope marker several hours prior to the planned surgery appears to be
      the optimum procedure in this method of SN identification in patients with breast
      cancer.

PMID- 16621428
TI  - Treatment of synchronous peritoneal carcinomatosis and liver metastases from
      colorectal cancer.
AB  - AIM: To report our experience of peritoneal carcinomatosis (PC) discovered during
      abdominal exploration in patients with liver metastases (LM). METHODS: Liver
      resection plus cytoreductive surgery were combined in 24 patients with LM and
      moderate PC from colorectal origin treated with a curative intent between January
      1993 and November 2003. RESULTS: The mean operative time was 357+/-112 min and
      median blood loss was 719 ml. One postoperative death occurred and postoperative
      morbidity was 58%. The mean hospital stay was 21.4+/-4.2 days. Three-year overall
      and disease-free survival rates were respectively 41.5% (confidence interval
      [CI]: 23-63) and 23.6% (CI: 11-45). Seven patients are disease-free with a mean
      follow-up of 27.8 months after their last surgery, 3 having a repeated
      hepatectomy. Three patients developed a peritoneal recurrence and 13 had
      recurrence in the liver. The only significant prognostic factor was a number of
      LMs of less than 3 (p < 0.01). CONCLUSION: A combined treatment of LM plus PC is
      feasible and is beneficial in selected patients presenting three or fewer
      metastases.

PMID- 16621429
TI  - Pattern of relapse in 290 patients with nonmetastatic Ewing's sarcoma family
      tumors treated at a single institution with adjuvant and neoadjuvant chemotherapy
      between 1972 and 1999.
AB  - AIMS: Evaluation of pattern of recurrences of 290 patients with an Ewing's
      sarcoma family tumor (ESFT), who relapsed after adjuvant or neoadjuvant
      chemotherapy. METHODS: Retrospective analysis at a median follow-up of 16.6 years
      (range: 5-32) from the primary therapy. RESULTS: There were 378 recurrences,
      treated by surgery, and/or chemotherapy, radiotherapy, or only palliative
      treatments. At the last control 18 patients were alive and free of disease 2.5 to
      20 years (median 12.1 year) from the last treatment, 4 were alive with
      uncontrolled disease, 2 died of second line chemotherapy-related toxicity, and
      266 died of the tumor 4 months to 20.5 years from the first relapse (median 3.2
      years). The 5-year event free survival after the last relapse and overall
      survival were 5.1 and 7.9%, respectively, and resulted significantly correlated
      with the time of first relapse, the site of first metastases, the treatment
      performed after relapse (all patients presently free of disease had been treated
      by surgery alone or combined with a second line chemotherapy) and for patients
      treated with neoadjuvant chemotherapy and locally by surgery, with the histologic
      response to preoperative chemotherapy. CONCLUSIONS: We confirm that the post
      relapse outcome of patients with ESFT who relapse after conventional treatment is
      very poor. Nonetheless specific subgroups of patients may be cured even after 2
      or 3 relapses: patients who relapse 2 or more years after primary treatment,
      patients who relapse with only lung metastases, and patients whose recurrences
      can be surgically treated.

PMID- 16621430
TI  - Neoadjuvant chemotherapy for locally advanced carcinoma of the lower oesophagus
      and oesophago-gastric junction.
AB  - AIMS: To evaluate a single unit's experience with neoadjuvant chemotherapy for
      treating locally advanced non-metastatic initially resectable and unresectable
      oesophago-gastric cancer. METHODS: The medical records of all patients with
      either locally advanced carcinoma of the lower oesophagus or cardia treated with
      neoadjuvant chemotherapy between August 1999 and January 2003 were reviewed.
      RESULTS: Sixty-four patients with initially resectable tumours (T2-3 or N+) and
      38 patients with initially unresectable tumours (T4 or M1a) received neoadjuvant
      chemotherapy (83% combination Epirubicin, Cisplatin and 5-Fluorouracil).
      Symptomatic grade III/IV toxicity was observed in 33% of patients. Chemotherapy
      was not completed in 20 patients because of death (5.9%) and inadequate tumour
      response/toxicity (13.7%). Forty-three patients (67.3%) with initially resectable
      tumours and 19 patients (50%) with initially unresectable tumours underwent
      surgery. CONCLUSIONS: Chemotherapy in this study was associated with appreciable
      toxicity. Patients with initially unresectable locally advanced disease can be
      downstaged with neoadjuvant chemotherapy.

PMID- 16621431
TI  - Comprehensive management of diffuse malignant peritoneal mesothelioma.
AB  - AIMS: In the past, diffuse malignant peritoneal mesothelioma (DMPM) has been
      regarded as a terminal condition. The length of the survival was dependent upon
      the aggressive versus indolent biology of the neoplasm, nevertheless cure was not
      considered as a reasonable expectation and the overall median survival was
      approximately one year. METHODS: A comprehensive literature review and a
      collection of pertinent data published on DMPM from the Washington Cancer
      Institute were used to construct this report. RESULTS: Recent publications from
      Bethesda MD, New York, Milan Italy, Lyon France and Washington DC have shown a
      remarkable prolongation in the median survival of this group of patients with
      approximately half the patients alive at 5 years. These prolonged survivors were
      treated with an intensive local-regional treatment strategy that included
      cytoreductive surgery (CRS) with peritonectomy and hyperthermic intraoperative
      intraperitoneal chemotherapy (HIIC) and some patients with early postoperative
      intraperitoneal chemotherapy (EPIC). As larger numbers of patients have been
      treated, clinical features by which to select patients most likely to benefit
      from this approach have been identified. Also, as the experience in the
      management of patients receiving these treatments has increased, the morbidity
      and mortality associated with their management is being reduced. CONCLUSIONS: A
      new standard of care involves surgical removal of large disease deposits combined
      with perioperative intraperitoneal chemotherapy. Knowledgeable management uses
      selection criteria and incurs low morbidity and mortality.

PMID- 16621432
TI  - Heated intra-operative intraperitoneal oxaliplatin alone and in combination with
      intraperitoneal irinotecan: Pharmacologic studies.
AB  - The results of four prospective clinical trials testing intraperitoneal
      chemohyperthermia (IPCH) are reported. The first one aimed at determining the
      appropriate dose of heated (42 degrees C) intraperitoneal oxaliplatin following
      complete resection of peritoneal carcinomatosis (PC) by studying its
      pharmacokinetics. The recommended dosage was set at 460 mg/m2 in 2 l/m2 of
      peritoneal instillation. The second trial is a phase 2 study on 24 patients with
      colorectal PC treated with the preceding regimen: the 2-year survival rate was
      74% after a minimal follow-up of 18 months. A second pharmacokinetic study using
      intraperitoneal oxaliplatin at the same dose but in hypotonic solutions did not
      show any survival advantage and was associated with an increase in complications.
      A third pharmacokinetic study was to determine the appropriate dose of
      intraperitoneal oxaliplatin combined with intraperitoneal irinotecan: the
      recommended dosage was 360 mg/m2 for each of the chemotherapy agents.

PMID- 16621433
TI  - Neoadjuvant treatment of gastric cancer with peritoneal dissemination.
AB  - AIMS: To report our experience of neoadjuvant intraperitoneal and systemic
      chemotherapy (NIPS) for patients having a complete resection of the primary
      gastric cancer and peritoneal carcinomatosis (PC). PATIENTS AND METHODS: Patients
      with advanced peritoneal dissemination of primary gastric cancer had the
      placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of
      docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a
      weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5
      fluorouracil were infused via a peripheral vein. A minimum of two cycles and up
      to six cycles of NIPS were used prior to cancer resection. At surgery a complete
      removal of the primary gastric cancer and the peritoneal implants by
      peritonectomy was attempted. RESULTS: Sixty-one patients were enrolled in the
      study. Thirty-nine had positive intraperitoneal cytology which reverted to
      negative cytology after treatment in 22. Thirty-eight showed a partial response.
      Thirty patients came to resection and 14 patients could be made disease-free.
      Median survival time of all patients was 14.4 months. Patients who received a
      complete resection had a median survival time of 20.4 months. Grade III/IV
      toxicities were not found after two courses of NIPS, but did develop in seven
      patients after more than three courses of NIPS. CONCLUSION: NIPS can downstage
      large volume peritoneal dissemination of gastric cancer. When combined with
      gastrectomy including peritonectomy a complete surgical resection was possible in
      one-quarter of the patients and resulted in a prolonged survival. This combined
      intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of
      consideration for phase III clinical investigations.

PMID- 16621434
TI  - Comparison of prostate cancer cell lines for androgen receptor-mediated reporter
      gene assays.
AB  - In order to select a better prostate cancer cell model for androgen receptor (AR)
      mediated reporter gene assays, we assessed the androgen response characteristics
      of three cell lines, LNCaP, PC3/AR(+) and 22Rv1, in this study. Both the mRNA and
      the proteins of AR and glucocorticoid receptor (GR) were expressed in all three
      cell lines. Among the three cell lines, only in LNCaP cells, DHT concentration
      dependently stimulated proliferation. DHT induced the luciferase activity in
      three cell lines which were transiently transfected with pMMTV-Luc, in a
      concentration-dependent manner. The maximum induction was 24.0-fold and 13.4-fold
      in 22Rv1 and in the LNCaP respectively. PC3/AR(+) were more sensitive to respond
      to DHT at a minimal concentration of 10(-12)M by 14.0-fold induction. The
      transcriptional activity induced with 10(-8)M DHT was inhibited about 50-75% in
      the PC3/AR(+) and 22Rv1, and 98% in the LNCaP, by vinclozolin. Dexamethasone
      concentration-dependently induced the luciferase activity in PC3 and 22Rv1, but
      not in the LNCaP. However, the response to dexamethasone in 22Rv1 was very weak
      compared to DHT. The (anti)androgencity of seven pyrethroids was assessed via an
      AR-mediated luciferase reporter assay. None of them showed the androgenic action
      in all three cell lines. Permethrin inhibited the DHT induced luciferase activity
      about 22%, 35.8% and 75.5% in 22Rv1, PC3/AR(+) and LNCaP, respectively. Based on
      results from in this study and cell line character, 22Rv1 cells seemed to be an
      appropriate model for the screening of androgenic endocrine disruptors, although
      it needs further studies with other steroid receptor and thyroid receptor.

PMID- 16621435
TI  - Effects of moniliformin in presence of cyclohexadepsipeptides on isolated
      mammalian tissue and cells.
AB  - Secondary metabolites produced by Fusarium spp. including beauvericin, enniatin
      and moniliformin are mycotoxins identified in cereal samples. The two
      cyclohexadepsipeptide mycotoxins beauvericin and enniatin have cytotoxic,
      antibiotic, insecticidal and ionophoric properties, while moniliformin primarily
      acts as a cardiotoxic mycotoxin. In this study, we examined the electromechanical
      and electrophysiological effects of moniliformin and moniliformin with ionophoric
      mycotoxins on cells (ventricular myocytes, Caco-2 cells) and in multicellular
      preparations (papillary muscles and terminal ilea of the guinea pig).
      Additionally, we investigated the influence of moniliformin on cell homeostasis
      in absence and presence of the cyclodepsipeptide mycotoxins (ventricular
      myocytes, Caco-2 cells). Experiments were performed using isometric measurements
      of contractility, intracellular microelectrode and patch-clamp techniques, and
      fluorescence imaging. While ionophoric cyclohexadepsipeptides affect action
      potential parameters and cell homeostasis, moniliformin did not change
      spontaneous rates of activity or cardiac action potentials. Furthermore,
      moniliformin had no effect on intracellular concentrations of ions and ATP, and
      did not affect pH. Moniliformin reduced contractility in papillary muscle,
      terminal ileum, the aorta and the pulmonary artery. However, moniliformin did not
      alter beauvericin and enniatin induced effects. From our studies, we conclude
      that moniliformin is not solely a cardiotoxic secondary metabolite, but also
      exerts its effects on smooth muscle. Moreover, there is no synergistic
      relationship between moniliformin and the concurrently produced
      cyclohexadepsipeptide mycotoxins beauvericin and enniatin.

PMID- 16621436
TI  - Peer influence and gender differences in problematic cannabis use among
      individuals with social anxiety.
AB  - Despite epidemiological reports indicating that individuals with social anxiety
      disorder (SAD) are at heightened risk for cannabis use disorders (CUD), there is
      a dearth of research investigating the mechanisms underlying the nature of this
      co-occurrence. The present study examined the role of a well-established risk
      factor for cannabis use, peer influence, on the relationship between symptoms of
      SAD and CUD in a non-referred sample (N = 123). Lifetime symptoms of SAD and CUD
      were assessed using a structured diagnostic interview. SAD symptoms were
      significantly correlated with CUD symptoms and this relationship was moderated by
      peer use of both alcohol and cannabis. Further, a gender effect indicated that
      the relationship between symptoms of SAD and CUD occurred only in women.
      Implications of these novel findings are discussed.

PMID- 16621437
TI  - Psychometric properties and construct validity of the Obsessive-Compulsive
      Inventory--Revised: Replication and extension with a clinical sample.
AB  - The present study examined the psychometric properties and construct validity of
      the Obsessive-Compulsive Inventory--Revised (OCI-R) with the aim of replicating
      and extending previous findings, and addressing limitations of previous
      investigations. Individuals with OCD (n = 167) and other anxiety disorders (n =
      155) completed the OCI-R, measures of OCD and related symptom severity, and
      measures of cognitive variables associated with OCD symptoms. Results indicate
      that the OCI-R is a psychometrically sound and valid measure of OCD and its
      various symptom presentations. Confirmatory factor analysis confirmed a six
      factor solution. The instrument also evidenced good convergent validity, and
      performed well in discriminating OCD from other anxiety disorders. Theoretically
      consistent patterns of associations between OCI-R symptom-based subscales and OCD
      related cognitive variables were found, and five of the six OCI-R subscales
      corresponded closely to identified OCD symptom dimensions. The OCI-R is
      recommended as an empirically validated instrument that can be used in a range of
      clinical and research settings for research on OCD.

PMID- 16621438
TI  - Repeated exposure to 20% CO2 challenge and risk for developing panic attacks: a
      controlled 6- and 12-month follow-up in a nonclinical sample.
AB  - Among ethical concerns associated with biological challenge procedures is the
      risk of potentiating panic attacks in otherwise healthy persons who have no
      history of panic. The aim of the present study was to determine if repeated
      exposure to 20% CO2 challenge increases the risk of developing panic attacks in a
      nonclinical sample. One hundred and fifty-five (39.5%) of 392 participants who
      underwent a 20% CO2 challenge procedure and 51 (63.0%) of 81 controls who
      breathed only room air were evaluated for panic attacks using the Panic Attack
      Questionnaire-Revised both at 6 and 12 months after the experiment. The
      percentage of participants who developed subsequent panic attacks did not differ
      significantly between the CO2 challenge group and the room air controls. High
      dose CO2 challenge does not increase the risk of subsequent panic attacks in
      nonclinical populations; it is a safe paradigm for use in psychopathology
      research with healthy individuals.

PMID- 16621439
TI  - Treatment attrition during group therapy for social phobia.
AB  - Psychological group treatments, such as behavioral or cognitive-behavioral
      therapy, are generally effective interventions for social phobia. However, a
      substantial number of individuals discontinue these treatments prematurely.
      Participant attrition can threaten the validity of treatment outcome studies if
      attrition during therapy does not occur randomly. In order to examine this issue,
      we studied 133 individuals with a principal diagnosis of social phobia who
      initiated a 12-week behavioral or cognitive-behavioral group treatment for social
      phobia. Thirty-four participants discontinued therapy prematurely. These dropouts
      were compared to treatment completers in demographic characteristics, Axis I and
      II psychopathology, and their attitude toward treatment. The results only showed
      a small difference between treatment completers and dropouts in their attitude
      toward treatment: dropouts rated the treatment rationale as less logical than
      completers at the beginning of treatment. No other differences between dropouts
      and completers were observed. Therefore, dropouts are unlikely to present a
      serious threat to the external validity of treatment outcome studies for social
      phobia.

PMID- 16621440
TI  - Behavioral inhibition and obsessive-compulsive disorder.
AB  - Behavioral inhibition is frequently cited as a vulnerability factor for
      development of anxiety. However, few studies have examined the unique
      relationship between behavioral inhibition and obsessive-compulsive disorder
      (OCD). Therefore, the current study addressed the relationship between behavioral
      inhibition and OCD in a number of ways. In a large unselected student sample,
      frequency of current OC symptoms was significantly correlated with retrospective
      self-reports of total levels of childhood behavioral inhibition. In addition,
      frequency of current OC symptoms was also significantly correlated with both
      social and nonsocial components of behavioral inhibition. Further, there was
      evidence for a unique relationship between behavioral inhibition and OC symptoms
      beyond the relationship of behavioral inhibition and social anxiety. In addition,
      results showed that reports of childhood levels of behavioral inhibition
      significantly predicted levels of OCD symptoms in adulthood. Finally, preliminary
      evidence suggested that behavioral inhibition may be more strongly associated
      with some types of OC symptoms than others, and that overprotective parenting may
      moderate the impact of behavioral inhibition on OC symptoms. The current findings
      suggest the utility of additional research examining the role of behavioral
      inhibition in the etiology of OCD.

PMID- 16621441
TI  - Brain's firewall: blood-brain barrier actively regulates neuroimmune information
      flow.

PMID- 16621442
TI  - Commentary on the allegation of scientific misconduct charge against Bucci et al.

PMID- 16621443
TI  - Neuroteratogens in man: an overview with special emphasis on the teratogenicity
      of antiepileptic drugs in pregnancy.
AB  - The most active growth and development of the human cerebrum and cerebellum
      occurs in the second half of pregnancy and in the first year of life. It is
      therefore not surprising that many teratogens may also affect development causing
      slight, moderate or even severe brain damage. The "classical" antiepileptic drugs
      (AEDs) valproic acid (VPA), phenytoin, phenobarbital, primidone and carbamazepine
      are all considered to be teratogenic. They may increase the rate of major
      congenital anomalies including neural tube defects (NTD), cause specific facial
      and other dysmorphic features--the "Anti Epileptic Drug Syndrome" (AEDS) and
      often some degree of mental impairment. Of these AEDs, the most teratogenic seems
      to be valproic acid, causing about 2% of NTD and an additional increase of 4-8%
      in major congenital anomalies. Phenytoin also increases the rate of various
      anomalies, but apparently not of NTD. Phenobarbital primidone and carbamazepine
      are also teratogenic and impair intellectual function but to a lesser extent than
      VPA and phenytoin. Cognition is mainly impaired in the children that also exhibit
      the AEDS. The impairment is slight to moderate, leaving the affected children
      with a close to borderline intelligence. Lamotrigine monotherapy in pregnancy
      seems to be relatively safe. In general, polytherapy is more dangerous to the
      fetus than monotherapy and, at least for VPA and lamotrigine, there seems to be a
      "threshold effect".

PMID- 16621444
TI  - ANP-mediated cGMP signaling and phosphodiesterase inhibition in the rat cervical
      spinal cord.
AB  - Natriuretic peptides (NP) and the corresponding receptors are present in the
      rodent spinal cord. We have studied the structures which respond to atrial
      natriuretic peptide, brain natriuretic peptide, or C-type natriuretic peptide
      with an increased synthesis of cGMP. NP-responsive cGMP-producing structures were
      observed in laminae I-III, and X, and in addition in ependymal cells, astrocytes
      and a subpopulation of dorsal root ganglion cells. As the cGMP concentration is
      controlled by the rate of synthesis and the rate of breakdown by
      phosphodiesterases, we studied NP-responsive structures in spinal cord slices
      incubated in the presence of different phosphodiesterase inhibitors. We studied
      EHNA and BAY 60-7550 as selective PDE2 inhibitors, sildenafil as a selective PDE5
      inhibitors, dipyridamole as a mixed type PDE5 and PDE10 inhibitor, rolipram as a
      PDE4 inhibitor, and SCH 81566 as a selective PDE9 inhibitor. Double
      immunostainings showed that cGMP-IR colocalized partial with the vesicular
      acetylcholine transporter molecule in lamina X, with Substance P in a
      subpopulation of neuronal fibers situated dorsolateral, and with a subpopulation
      of CGRP-IR dorsal root ganglion neurons. Colocalization of cGMP-IR was absent
      with parvalbumin, synaptophysin, and the vesicular transporter molecules for GABA
      and glutamate. It is concluded that NPs in the spinal cord are probably involved
      in integrating intersegmental sensory processing in the spinal cord although the
      greater part of the NP-responsive cGMP-producing fibers could not be
      characterized. PDE2, 5, and 9 are involved in regulating NP-stimulated cGMP
      levels in the spinal cord. NPs may have a role in regulating cerebrospinal fluid
      homeostasis.

PMID- 16621445
TI  - The role of phosphodiesterase isoforms 2, 5, and 9 in the regulation of NO
      dependent and NO-independent cGMP production in the rat cervical spinal cord.
AB  - NO-responsive, cGMP-producing structures are abundantly present in the cervical
      spinal cord. NO-mediated cGMP synthesis has been implicated in nociceptive
      signaling and it has been demonstrated that cGMP has a role establishing synaptic
      connections in the spinal cord during development. As cGMP levels are controlled
      by the activity of soluble guanylyl cyclase (synthesis) and the phosphodiesterase
      (PDE) activity (breakdown), we studied the influence of PDE activity on NO
      stimulated cGMP levels in the rat cervical spinal cord. cGMP-immunoreactivity
      (cGMP-IR) was localized in sections prepared from slices incubated in vitro. A
      number of reported PDE isoform-selective PDE inhibitors was studied in
      combination with diethylamineNONOate (DEANO) as a NO-donor including isobutyl
      methylxanthine (IBMX) as a non-selective PDE inhibitor. We studied 8-methoxy-IBMX
      as a selective PDE1 inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and
      BAY 60-7550 as selective PDE2 inhibitors, sildenafil as a selective PDE5
      inhibitor, dipyridamole as a mixed type PDE5 and PDE10 inhibitor, rolipram as a
      PDE4 inhibitor, and SCH 81566 as a selective PDE9 inhibitor. cGMP-IR structures
      (nerve fibers, axons, and terminals) were characterized using the following
      neurochemical markers: vesicular transporter molecules for acetylcholine, GABA,
      and glutamate (type 1 and type 2), parvalbumin, glutamate transporter molecule
      EAAT3, synaptophysin, substance P, calcitonin gene-related peptide, and isolectin
      B4. Most intense cGMP-IR was observed in the dorsal lamina. Ventral motor neurons
      were devoid of cGMP-IR. cGMP-IR was observed in GABAergic, and glutamatergic
      terminals in all gray matter laminae. cGMP-IR was abundantly colocalized with
      anti-vesicular glutamate transporter 2 (vGLUT2), however not with the anti
      vesicular glutamate transporter 1 (vGLUT1), suggesting a functional difference
      between structures expressing vGLUT1 or vGLUT2. cGMP-IR did not colocalize with
      substance P- or calcitonin-gene related peptide-IR structures, however did
      partially colocalize with isolectin B4 in the dorsal horn. cGMP-IR in cholinergic
      structures was observed in dorsal root fibers entering the spinal cord,
      occasionally in laminae 1-3, in laminae 8 and 9 in isolated boutons and in the C
      type terminals, and in small cells and varicosities in lamina 10. This latter
      observation suggests that the proprioceptive interneurons arising in lamina 10
      are also NO-responsive. No region-specific nor a constant co-expression of cGMP
      IR with various neuronal markers was observed after incubation of the slices with
      one of the selected PDE inhibitors. Expression of the mRNA of PDE2, 5, and 9 was
      observed in all lamina. The ventral motor neurons and the ependymal cells lining
      the central canal expressed all three PDE isoforms. Incubation of the slices in
      the presence of IBMX, DEANO in combination with BAY 41-2272, a NO-independent
      activator of soluble guanylyl cyclase, provided evidence for endogenous NO
      synthesis in the slice preparations and enhanced cGMP-IR in all lamina. Under
      these conditions cGMP-IR colocalized with substance P in a subpopulation of
      substance P-IR fibers. It is concluded that NO functions as a retrograde
      neurotransmitter in the spinal cord but that also postsynaptic structures are NO
      responsive by producing cGMP. cGMP-IR in a subpopulation of isolectin B4 positive
      fibers and boutons is indicative for a role of NO-cGMP signaling in nociceptive
      processing. cGMP levels in the spinal cord are controlled by the concerted action
      of a number of PDE isoforms, which can be present in the same cell.

PMID- 16621446
TI  - The effect of acetyl-L-carnitine administration on persons with Down syndrome.
AB  - Since previous investigations reported improvements in cognition of patients with
      dementia after acetyl-L-carnitine therapy and since there is an increased risk
      for persons with Down syndrome to develop Alzheimer disease, this study was
      designed to investigate the effect of acetyl-L-carnitine administration on
      neurological, intellectual, and social functions in adults with Down syndrome. In
      this double-blind study we enrolled 40 individuals with Down syndrome and
      administered acetyl-L-carnitine to the study group during a six months period.
      Specified examinations and psychological tests were given to persons in both the
      study and control groups at the start of the investigation and at 3, 6, and 9
      months. A detailed analysis of the data revealed that acetyl-L-carnitine
      administration did not enhance central nervous system functions and that it did
      not benefit persons with Down syndrome.

PMID- 16621447
TI  - Elevated levels of soluble CD40 ligand (sCD40L) in serum of patients with
      systemic autoimmune diseases.
AB  - The CD40-CD40L costimulatory pathway is involved in the evolution of many
      autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid
      arthritis (RA) and Sjogren's syndrome (SS). Increased levels of sCD40L in the
      serum have been associated with disease activity in SLE. The aim of this study
      was to investigate the role of sCD40L in the development of lupus nephritis and
      examine its possible association with cryoglobulinemia in Sjogren's syndrome. We
      used a 2-site sandwich ELISA to measure the levels of sCD40L in sera, from 64
      patients with SLE, RA and SS and 17 healthy blood donors. Biological specimens
      from the affected tissues such as urine from patients with lupus nephritis and
      saliva from patients with SS were also tested. In this regard, paired sera and
      first morning urine samples from 6 SLE patients (3 with active lupus nephritis
      and 3 with inactive lupus nephritis) were tested with the sCD40L ELISA protocol
      as well as paired sera and salivary samples from 5 patients with SS and
      cryoglobulinemia, 5 patients with SS and anti-Ro or anti-La autoantibodies and 5
      age-matched healthy control donors. We also examined possible correlations of
      sCD40L levels with several laboratory and clinical parameters in SS and SLE. We
      found that sera from SLE and SS patients had significantly higher levels of
      sCD40L compared to sera from healthy control donors. No sCD40L was detected, in
      urine samples of patients with either active or inactive nephritis and in
      salivary samples from SS patients or normal subjects. Soluble CD40L is elevated
      in sera of SS and SLE patients but further investigation is needed to determine
      its possible role in SLE nephritis and Sjogren's syndrome.

PMID- 16621448
TI  - Inhibition of the rat brain sodium channel Nav1.2 after prolonged exposure to
      gabapentin.
AB  - Prolonged exposure of neurons to gabapentin inhibits repetitive firing of Na(+)
      dependent action potentials. Here, we studied the effect of such prolonged
      exposure to gabapentin on a rat sodium channel, Nav1.2. After 3 days of
      continuous incubation with gabapentin (10-1000 microM), Nav1.2 current density
      was decreased dose-dependently relative to untreated cells. The reduction was 57%
      at 30 microM gabapentin, while higher concentrations (100-1000 microM) did not
      result in greater effects. Prolonged treatment with gabapentin also caused the
      channel to inactivate at more hyperpolarized potentials. These effects provide a
      mechanistic basis for the inhibition of Na(+)-dependent repetitive firing upon
      prolonged exposure to gabapentin and may contribute to its anticonvulsant
      activity.

PMID- 16621449
TI  - Contralateral 80-280 Hz EEG ripples and hippocampal single unit discharge
      inhibition in response to acute tetanization of rat right caudate putamen in
      vivo.
AB  - Clinically, 4-8 Hz (or 30-80 Hz) stimulation of the caudate nucleus ceases (or
      enhances) the neocortical and hippocampal epileptiform activities of the epilepsy
      patients. Possibly, electric stimulation of the caudate nucleus could produce
      epilepsy. In order to prove this point we delivered the acute tetanization (60
      Hz, 2s, 0.4-0.6 mA) into the rat right caudate putamen nucleus (ATRC) and
      examined bilateral neocortical EEG and hippocampal unit discharges in vivo. The
      results demonstrated that: (1) 80-280 Hz EEG ripples could be evoked bilaterally,
      and more stronger on the contralateral side. And the maximum amplitudes of the
      power spectra (microV2/Hz) have higher shifting variability among multiple
      contralateral EEG ripples. (2) The EEG ripples were coupled contralaterally with
      the hippocampal neuronal firing inhibition. (3) An episode of 10-15 Hz EEG
      oscillations was ipsilaterally coupled with rhythmic hippocampal neuronal bursts.
      It suggested that the hemispheric reactions of neocortical EEG and hippocampal
      neuronal discharges are lateralized in response to the stimulation. It implies
      that the epileptic network activities were reorganized by the ATRC. Neocortical
      EEG ripples, called as seizure-like fast oscillations, were repetitively evoked
      by the ATRC.

PMID- 16621451
TI  - Effects of uridine in models of epileptogenesis and seizures.
AB  - Due to the limited efficacy and side effects of current antiepileptic drugs
      (AEDs), the search for new therapeutic agents is critical. Uridine, a possible
      endogenous antiepileptic modulator, has been demonstrated to have anticonvulsant
      effects in some models of epilepsy, but not others. In this study, we examined
      possible neuroprotective effects of uridine by administering the agent following
      lithium-pilocarpine induced status epilepticus. The effects of uridine were
      assessed on EEG patterns, visual-spatial memory in the water maze and
      histopathology. There was a trend for reduced EEG spike frequency, improved
      visual spatial memory and better histology score in rats receiving uridine. The
      antiepileptogenic and anticonvulsant effects of uridine were studied by
      administering uridine to rats undergoing rapid kindling or following full
      kindling. In the rapid kindling models, uridine had a moderate antiepileptogenic
      and anticonvulsant effect. These results suggest uridine may have potential to
      aid in the prevention and treatment of epilepsy.

PMID- 16621452
TI  - Relevance of cellular infiltrate and cytokines in polymorphic eruption of
      pregnancy (PEP).

PMID- 16621450
TI  - Diverse mechanisms of antiepileptic drugs in the development pipeline.
AB  - There is a remarkable array of new chemical entities in the current antiepileptic
      drug (AED) development pipeline. In some cases, the compounds were synthesized in
      an attempt improve upon the activity of marketed AEDs. In other cases, the
      discovery of antiepileptic potential was largely serendipitous. Entry into the
      pipeline begins with the demonstration of activity in one or more animal
      screening models. Results from testing in a panel of such models provide a basis
      to differentiate agents and may offer clues as to the mechanism. Target activity
      may then be defined through cell-based studies, often years after the initial
      identification of activity. Some pipeline compounds are believed to act through
      conventional targets, whereas others are structurally novel and may act by novel
      mechanisms. Follow-on agents include the levetiracetam analogs brivaracetam and
      seletracetam that act as SV2A-ligands; the valproate-like agents valrocemide,
      valnoctamide, propylisopropyl acetamide, and isovaleramide; the felbamate analog
      flurofelbamate, a dicarbamate, and the unrelated carbamate RWJ-333369; the
      oxcarbazepine analog licarbazepine, which probably acts as a use-dependent sodium
      channel blockers, and its prodrug acetate BIA 2-093; various selective partial
      benzodiazepine receptor agonists, including ELB139, which is a positive
      allosteric modulator of alpha3-containing GABA(A) receptors. A variety of AEDs
      that may act through novel targets are also in clinical development: lacosamide,
      a functionalized amino acid; talampanel, a 2,3-benzodiazepine selective
      noncompetitive AMPA receptor antagonist; NS1209, a competitive AMPA receptor
      antagonist; ganaxolone, a neuroactive steroid that acts as a positive modulator
      of GABA(A) receptors; retigabine, a KCNQ potassium channel opener with activity
      as a GABA(A) receptor positive modulator; the benzanilide KCNQ potassium channel
      opener ICA-27243 that is more selective than retigabine; and rufinamide, a
      triazole of unknown mechanism.

PMID- 16621453
TI  - Autocrine production of biologically active hepatocyte growth factor (HGF) by
      injured human skin.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a potent regenerative factor
      involved in wound healing. Previous studies have shown that mesenchymal cells
      produce HGF, stimulating epithelial cells in a paracrine fashion. OBJECTIVE: To
      examine whether autocrine HGF production by keratinocytes can occur upon skin
      injury. METHODS: A 31-year-old male patient sustained a burn affecting 80% of his
      total body surface area. Biopsies were taken from intact skin near the injured
      area, and skin keratinocytes were separated and cultured. Conditioned medium from
      keratinocytes was analyzed for HGF by ELISA, surface plasmon resonance (SPR), and
      dot blotting. Binding of HGF from conditioned medium to its receptor, c-Met, was
      compared with recombinant HGF by SPR. Finally, we examined the motogenic effect
      on mouse transformed skin epithelial cells (CCL-53.1) of HGF from conditioned
      medium. RESULTS: HGF was detected in the cultured keratinocyte medium. Similar to
      recombinant HGF, HGF from conditioned medium had a high affinity for dextran
      sulfate and albumin, and the same epitopes were engaged by the interaction of HGF
      with the c-Met receptor. The conditioned medium from keratinocytes obtained from
      the burn patient, but not medium from keratinocytes obtained from healthy
      volunteers, accelerated the motogenesis of CCL-53.1 cells. Unexpectedly, anti-HGF
      antibodies did not prevent this effect. However, anti-c-Met antibodies completely
      inhibited the motogenic effect. CONCLUSION: Upon injury, human skin keratinocytes
      might produce biologically active HGF in an autocrine fashion. This HGF might
      have different structural and/or biological properties from HGF produced by
      mesenchymal cells.

PMID- 16621454
TI  - ATP2C1 is specifically localized in the basal layer of normal epidermis and its
      depletion triggers keratinocyte differentiation.
AB  - BACKGROUND: ATP2C1 is a calcium/manganese-ATPase localized in the Golgi apparatus
      and known as responsible gene for Hailey-Hailey disease. But its localization and
      roles in the epidermis are not fully elucidated. OBJECTIVE: To explore the
      localization and biological role of ATP2C1 in normal epidermis in terms of
      differentiation states. METHODS: We examined the immunohistochemical distribution
      of ATP2C1 in normal epidermis and measured the expression of ATP2C1 in cultured
      keratinocytes following forced detachment from culture dish or following
      treatment with high concentrations of calcium. Furthermore, we knockdown ATP2C1
      expression in cultured keratinocytes by using RNA interference procedure to
      abrogate cation accumulation in cell organelles. RESULTS: ATP2C1 is specifically
      localized at the basal cell layer in normal epidermis. Neither detachment of
      keratinocyte from culture dish nor treatment with high concentrations of calcium
      suppressed ATP2C1 expression, while both procedures induced differentiation
      markers, K10 keratin and involucrin. In contrast, knockdown of ATP2C1 induced
      these differentiation markers of cultured keratinocytes. Furthermore, treatment
      of keratinocytes with a calcium ionophore, A23187, did not up-regulate
      differentiation markers of keratinocytes, while a more manganese selective
      ionophore Br-A23187 up-regulated these differentiation markers. CONCLUSION: Our
      results suggest that ATP2C1 plays an essential role for basal keratinocytes to
      keep in the undifferentiated state and that its reduction evokes differentiation
      and up-localization to suprabasal layers most likely via the manganese starvation
      in the Golgi apparatus of keratinocytes.

PMID- 16621455
TI  - Genomic fingerprinting of Burkholderia pseudomallei and B. mallei pathogens with
      DNA array based on interspecies sequence differences obtained by subtractive
      hybridization.
AB  - The ability to rapidly and efficiently identify causative agents of dangerous
      human and animal diseases is a prerequisite to diagnosis, prophylaxis and
      therapy. Such identification systems can be developed based on DNA markers
      enabling differentiation between various bacterial strains. One source of these
      markers is genetic polymorphism. An efficient method for detecting the most
      stable polymorphisms without knowledge of genomic sequences is subtractive
      hybridization. In this work we report an approach to typing of Burkholderia
      pseudomallei and B. mallei that cause melioidosis and glanders, respectively.
      Typing is based on hybridization of bacterial genomes with a DNA array of genomic
      markers obtained using subtractive hybridization. The array comprised 55 DNA
      fragments which distinguished the genomes of B. pseudomallei C-141 and B. mallei
      C-5 strains, and it was used to test 28 radioactively labeled B. pseudomallei
      strains and 8 B. mallei strains. Each strain was characterized by a specific
      hybridization pattern, and the results were analyzed using cluster analysis. 18
      patterns specific to B. pseudomallei and 6 patterns specific to B. mallei were
      found to be unique. The data allowed us to differentiate most studied B.
      pseudomallei variants from one another and from B. mallei strains. It was
      concluded that DNA markers obtained by subtractive hybridization can be
      potentially useful for molecular typing of B. pseudomallei and B. mallei strains,
      as well as for their molecular diagnosis. The method reported can be easily
      adapted for use both with DNA arrays and DNA microarrays with fluorescent probes.

PMID- 16621456
TI  - First report of CTX-M-15 and CTX-M-3 beta-lactamases among clinical isolates of
      Enterobacteriaceae in Bejaia, Algeria.
AB  - We assessed the prevalence and phenotypic characteristics of extended-spectrum
      beta-lactamase producers among 365 clinical isolates of members of the family
      Enterobacteriaceae recovered from two hospitals in Bejaia, Algeria, between March
      2004 and April 2005. Twenty-one strains were resistant to cefotaxime and/or
      ceftazidime. A double-disk synergy test yielded a positive result in five cases
      (three Escherichia coli, one Klebsiella pneumoniae and one Enterobacter cloacae).
      Using polymerase chain reaction and sequencing, the three E. coli isolates and
      the K. pneumoniae isolate were found to produce extended-spectrum beta-lactamase
      CTX-M-15 and the E. cloacae isolate produced CTX-M-3. The three CTX-M-15
      producing E. coli isolates were not isolated in the same wards, although
      genotyping by randomly amplified polymorphic DNA analysis revealed that they were
      clonally related. The bla(CTX-M-15) genes were transferred from E. coli by
      conjugation, whilst conjugative transfer of bla(CTX-M) genes from K. pneumoniae
      and E. cloacae was not detectable.

PMID- 16621457
TI  - Treatment of murine pneumonic Francisella tularensis infection with gatifloxacin,
      moxifloxacin or ciprofloxacin.
AB  - The efficacies of gatifloxacin and moxifloxacin were assessed in a BALB/c mouse
      model of pneumonic tularemia and compared with the efficacy of ciprofloxacin. The
      rate of relapse following dexamethasone treatment was also investigated. Mice
      were given 100 mg/kg of the antibiotic by oral administration twice daily for 14
      days following an aerosol challenge. All three fluoroquinolones prevented disease
      during the treatment period, but significant failure rates occurred after the
      cessation of therapy. Both gatifloxacin and moxifloxacin were more effective than
      ciprofloxacin at reducing late mortality. Fluoroquinolones may therefore be
      considered useful candidates for the treatment of pneumonic tularemia.

PMID- 16621458
TI  - Antibiotic susceptibilities of Yersinia enterocolitica recovered from children
      over a 12-year period.
AB  - Antibiotic susceptibility testing by the microdilution technique was performed on
      184 Yersinia enterocolitica isolates recovered from children with gastroenteritis
      in the Detroit area during a 12-year period. The majority of isolates were
      resistant to ampicillin, ticarcillin and cefazolin. The most active agents were
      cefotaxime, ceftriaxone, cefepime, gentamicin, tobramycin,
      sulphamethoxazole/trimethoprim, imipenem and ciprofloxacin. Cefotaxime and
      ceftriaxone were effective in the treatment of bacteraemia in 12 patients.

PMID- 16621459
TI  - Antiviral activity of cyclosaligenyl prodrugs of the nucleoside analogue
      bromovinyldeoxyuridine against herpes viruses.
AB  - A series of 42 lipophilic bromovinyldeoxyuridine monophosphates (BVDUMPs) are
      presented as potential prodrugs of the antiviral agent (E)-5-(2-bromovinyl)-2'
      deoxyuridine (BVDU). The 5'-cycloSal-masking group technique has been applied to
      this cyclic nucleoside analogue to achieve delivery of the monophosphate of BVDU
      inside the target cells. The new substances have been tested for their antiviral
      activity against herpes simplex virus types 1 and 2 (HSV-1 and -2), thymidine
      kinase-deficient (TK(-)) HSV-1, varicella-zoster virus (VZV), human
      cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). The XTT-based tetrazolium
      reduction assay EZ4U (for HSV), the plaque inhibition test (for VZV and HCMV) and
      a DNA hybridisation assay (for EBV) were used to assess antiviral activity. The
      results indicate that cycloSal-BVDUMP triesters proved to be potent and selective
      inhibitors of HSV-1 comparable with aciclovir. VZV replication was inhibited by
      very low concentrations, and two substances had a slightly better anti-VZV
      activity than the parent compound BVDU. No antiviral effect could be demonstrated
      against TK(-)-HSV-1, HSV-2 and HCMV, most likely owing to the lack of
      phosphorylation to BVDU diphosphate. Most remarkably, several cycloSal-BVDUMP
      triesters yielded promising anti-EBV activity whereas the parent compound BVDU
      was entirely inactive.

PMID- 16621460
TI  - Effect of sodium diclofenac on the bioavailability of amoxicillin.
AB  - The aim of this study was to evaluate the effect of sodium diclofenac on the
      bioavailability of amoxicillin. In this randomised, crossover study with a 1-week
      washout period, 20 volunteers received a 2g oral dose of amoxicillin (Amoxil)
      (Group 1) or a 2g oral dose of amoxicillin with 100 mg of sodium diclofenac
      (Voltaren) (Group 2). Blood samples were collected at 0, 0.25, 0.5, 1, 1.5, 2,
      2.5, 4, 6, 8, 12 and 24h following drug administration. High-performance liquid
      chromatography with ultraviolet detection was used to quantify plasma amoxicillin
      concentrations. Bioassay (Micrococcus luteus ATCC 9341) was performed to verify
      the antimicrobial efficacy of amoxicillin in vitro. The pharmacokinetic
      parameters area under the plasma concentration-time curve (AUC), maximum plasma
      concentration observed during the 24-h study period (C(max)) and renal clearance
      (CL) were analysed by analysis of variance, and time at which C(max) occurred
      (T(max)) and volume of distribution (VD) were analysed by Wilcoxon test (P<0.05).
      For Group 1, the mean (+/- standard deviation) AUC(0-24), C(max) and T(max)
      values were 3391.8+/-1186.7 microg min/mL, 17.3+/-6.5 microg /mL and 121.5+/-20.6
      min, respectively; and for Group 2, the values were 2918.4+/-1024.8 microg
      min/mL, 15.5+/-5.8 microg /mL and 136.5+/-30.0 min, respectively. Lower values of
      AUC and C(max) were observed for Group 2 (P<0.05). CL of amoxicillin increased
      (P< 0.05) by 18.5% in Group 2, suggesting that sodium diclofenac may interfere
      with amoxicillin renal excretion. In conclusion, sodium diclofenac can
      significantly reduce the bioavailability of amoxicillin.

PMID- 16621461
TI  - Treatment of implant-associated infections with moxifloxacin: an animal study.
AB  - The efficacy of moxifloxacin in the treatment of an implant-associated infection
      by Staphylococcus aureus was compared with vancomycin in an animal study. The
      femoral medullary cavity of 36 Wistar rats was contaminated with S. aureus (ATCC
      29213) and a metal device was implanted. After treatment for 14 days with
      moxifloxacin (2 x 10 mg/kg/day) or vancomycin (2 x 15 mg/kg/day), the bacterial
      counts (colony-forming units) in the periprosthetic bone, the soft tissue and the
      implant-associated biofilm were measured. Compared with the control group,
      moxifloxacin achieved a highly significant decrease in the microbial counts in
      the bone and soft tissue and in the biofilm (P<0.001). Moreover, the efficacy of
      moxifloxacin was significantly greater than that of vancomycin (P<0.01).
      Vancomycin did not reduce the microbial count significantly compared with the
      control group (P>0.05). The results justify further investigations of the
      treatment of implant-associated infections due to S. aureus with moxifloxacin.

PMID- 16621462
TI  - Characterisation of antimicrobial resistance patterns and class 1 integrons among
      Escherichia coli and Salmonella enterica serovar Choleraesuis strains isolated
      from humans and swine in Taiwan.
AB  - Escherichia coli isolates from humans (n=110) and swine (n=61) and Salmonella
      enterica serovar Choleraesuis isolates (n=95) from swine in southern Taiwan were
      characterised for antimicrobial resistance patterns and class 1 integrons. All E.
      coli isolates and S. Choleraesuis isolates were multidrug resistant and
      demonstrated high resistance to beta-lactams, aminoglycosides, tetracycline,
      sulfonamides, spectinomycin, chloramphenicol and nalidixic acid. By polymerase
      chain reaction and DNA sequencing, 104 (61%) E. coli isolates and 31 (33%) S.
      Choleraesuis isolates were found to carry class 1 integrons. The gene cassette
      array dfrA12-orfF-aadA2 was the most prevalent (24%) among the human and swine E.
      coli isolates, whilst the gene cassette array dfrA12-orfF-aadA2-sul1 was the most
      prevalent (24%) among S. Choleraesuis strains. For E. coil isolates, all class 1
      integrons were located on conjugated plasmids. Meanwhile, human and swine E. coli
      isolates carrying identical gene cassettes were genetically unrelated. Our
      results revealed that multidrug resistance and class 1 integrons were widely
      present in E. coli and S. Choleraesuis isolates obtained in Taiwan and that class
      1 integrons might play an important role in contributing to the horizontal
      transfer of antimicrobial resistance.

PMID- 16621463
TI  - Molecular epidemiology of urinary tract isolates of vancomycin-resistant
      Enterococcus faecium from North America.
AB  - Vancomycin-resistant Enterococcus faecium (VRE) are a common cause of nosocomial
      infections and are important agents of gastrointestinal colonisation. As the
      prevalence of VRE in hospitalised patients continues to increase, implementation
      of appropriate infection control measures requires routine surveillance of VRE
      transmission patterns. The purpose of the present study was to investigate the
      molecular epidemiology of VRE isolates within the USA and Canada. Two hundred and
      eighty-three urinary tract isolates of VRE were collected in the year 2000 from
      ten Canadian hospitals and 28 US tertiary care medical centres representing seven
      of the nine geographic regions of the United States Bureau of the Census. The in
      vitro activity of vancomycin, teicoplanin and nine comparators was determined by
      broth microdilution. The genetic relatedness among isolates was evaluated by
      pulsed-field gel electrophoresis (PFGE). Resistance rates (intermediate and
      resistant) were 100% for vancomycin and 78.7% for teicoplanin. Resistance was
      lowest with linezolid, chloramphenicol and nitrofurantoin at 0.3%, 0.3% and 0.5%,
      respectively. PFGE revealed that genetic heterogeneity amongst isolates from each
      of the medical centres varied considerably. Despite some intracentre and
      intercentre VRE dissemination, the present study found no evidence for the
      emergence of a dominant clonal strain. This suggests that the spread of VRE
      within North America is a complex process involving both the horizontal transfer
      of glycopeptide resistance determinants and polyclonal dissemination.

PMID- 16621465
TI  - Resistance mechanisms in fluconazole-resistant Candida albicans isolates from
      vaginal candidiasis.
AB  - Candida albicans is the most frequently identified yeast species causing mycotic
      vaginitis. A significant number of vaginal yeast isolates are resistant to azole
      antifungal agents in vitro. Here we investigated the molecular mechanisms of
      resistance in 22 randomly selected fluconazole-resistant vaginal C. albicans
      isolates. Twelve isolates in this collection were found to be cross-resistant to
      itraconazole and 15 to voriconazole. Most of them also displayed decreased
      susceptibility to terbinafine. Northern blot analyses revealed overexpression of
      the MDR1 gene in all isolates, which in some isolates was accompanied by elevated
      levels of CDR1/CDR2 and ERG11 expression. Sequence analysis of the polymerase
      chain reaction-amplified ERG11 gene of selected azole-resistant isolates
      identified D116E and V488I amino acid alterations in Erg11p that are known to be
      conserved in fluconazole-resistant strains. The results demonstrate that
      decreased susceptibilities of vaginal yeast isolates to clinically used azole
      derivatives are the result of a combination of several molecular mechanisms
      involving drug efflux and alterations in the structure or cellular amount of 14
      alpha-lanosterol demethylase.

PMID- 16621466
TI  - Wnt2 is a direct downstream target of GATA6 during early cardiogenesis.
AB  - The GATA4, 5 and 6 subfamily of transcription factors are potent transactivators
      of transcription expressed within the precardiac mesoderm. However, little is
      known of the immediate downstream targets of GATA-factor regulation during the
      earliest stages of cardiogenesis. Using the P19-CL6 embryonal carcinoma (EC) cell
      line as an in vitro model of cardiogenesis, we show that GATA6 is the most
      abundantly expressed of the GATA factors in presumptive cardiac cells.
      Consequently, we performed a microarray screen comparing mRNA from control EC
      cells, early in the cardiac differentiation pathway, with those in which GATA6
      had been overexpressed. These studies identified 103 genes whose expression
      changed significantly and this was verified in a representative array of these
      genes by real-time RT-PCR. We show that early cardiac expression of one of these
      genes, Wnt2, mirrors that of GATA6 in vitro and in vivo. In addition, its
      upregulation by GATA6 in differentiating EC cells is mediated by the direct
      binding of GATA-factor(s) to the cognate Wnt2 promoter, suggesting Wnt2 is an
      immediate downstream target of GATA-factor regulation during early cardiogenesis.

PMID- 16621467
TI  - 14N nuclear quadrupole resonance of some sulfa drugs.
AB  - The 14N nuclear quadrupole double resonance spectra of different polymorphs of
      sulfanilamide, sulfadiazine, sulfamerazine and sulfamethazine have been measured
      and the 14N quadrupole coupling tensors have been determined. The obtained 14N
      spectra are compared with those of other sulfa drugs like sulfathiazole. It is
      shown that different polymorphs can be easily discriminated. The application of
      this technique for non-destructive analysis, polymorph determination and quality
      control in the production of pharmaceuticals is stressed.

PMID- 16621468
TI  - Solid-state NMR studies of 17O-enriched pyrophosphates.
AB  - For the first time, 17O NMR studies were performed on 17O-enriched crystalline
      pyrophosphates (magnesium-, sodium- and barium-pyrophosphate) by means of triple
      quantum magic-angle spinning (3QMAS) and double-rotation (DOR) in the high
      external field of 17.6 T. Oxygen atoms in bridging positions (P-OB-P) exhibit a
      significant higher quadrupole coupling constant compared to oxygen atoms in
      terminal positions (P-OT). With increasing cationic radius a higher value of the
      chemical shift of the terminal oxygen atoms is observed.

PMID- 16621469
TI  - A fractal analysis approach to viscoelasticity of physically cross-linked barley
      beta-glucan gel networks.
AB  - The structure and gelation kinetics of mixed linkage barley beta-glucans of
      varying Mw have been investigated. The fractal concept has been applied to
      describe the structure development of barley beta-glucan gels using a scaling
      model and dynamic rheometry data. The model supports that the gel structure
      consists of fractal clusters that upon aggregation lead to a three-dimensional
      network. The analysis showed that with increasing Mw a denser (more packed)
      network is formed as indicated by the corresponding fractal dimension (df)
      values. The microelastic parameter of the model, alpha, showed that all gel
      structures were in the transition regime implying structural reordering upon
      ageing. The description of the microstructure as a fractal network seems to be
      able to explain syneresis and other observations from large deformation testing
      of such systems. The molecular treatment of the gelation kinetics suggests that
      the gelling behavior is governed by the probability of collision of chain
      fragments with consecutive cellotriosyl units. This is greater for small chains
      due to their higher diffusion rates, for chains having lower amounts of cellulose
      like fragments and finally for those showing smaller degree of intrachain
      interactions. As a result, the faster gelling systems exhibit lower fractal
      dimensionality (more disordered systems) something that is in accordance with
      current kinetic theories.

PMID- 16621470
TI  - Does the nanometre scale topography of titanium influence protein adsorption and
      cell proliferation?
AB  - To investigate the influence of titanium films with nanometre scale topography on
      protein adsorption and cell growth, three different model titanium films were
      utilized in the present study. The chemical compositions, surface topographies
      and wettability were investigated by using X-ray photoelectron spectroscopy
      (XPS), atomic force microscopy (AFM) and water contact angle measurement,
      respectively. The films share the same surface chemistry but exhibit different
      topographies on a nanometre scale. Thus, they act as model systems for biological
      studies regarding surface topography effects. The films were obtained by varying
      the deposition rate and the film thickness, respectively. These films displayed
      nanometre scale surface roughness (root mean square roughness, R(rms)) from 2 to
      21 nm over areas of 50 microm x 50 microm, with different grain sizes at their
      surfaces. Albumin and fibrinogen adsorption on these model titanium films were
      performed in this study. Bicinchoninic acid assay was employed to determine the
      amount of adsorbed protein on titanium film surfaces. No statistically
      significant differences, however, were observed for either albumin or fibrinogen
      adsorption between the different groups of titanium films. No statistically
      significant influence of surface roughness on osteoblast proliferation and cell
      viability was detected in the present study.

PMID- 16621471
TI  - A simple and convenient approach for isolating RNA from highly viscous plant
      tissue rich in polysaccharides.
AB  - RNA isolation is a prerequisite to the study of gene expression of herbaceous
      plant Dendrobium nobile under an environmental stress. However, RNA isolation is
      difficult in the plant of genus Dendrobium, which is relatively viscous, due to
      being rich in polysaccharides. The common protocols for RNA isolation are tedious
      and usually result in poor yields when applied to D. nobile. Here, we describe a
      simple and convenient method for high quality total RNA extraction from D.
      nobile. Main procedures are as follows: smashing plant tissue and cell wall by
      means of pre-cooled citrate homogenization, cleaving cell membrane by using
      guanidine hydrochloride lysis buffer, removing proteins, polyphenols and
      polysaccharides by acidic phenol/chloroform. It is particularly useful for
      processing large numbers of plant samples. The whole process can be completed
      within 2.5 h. The extracted RNA is suitable for applications such as RT-PCR,
      Northern analysis and screening of differential expression genes.

PMID- 16621472
TI  - Using highly carboxylated microspheres to simplify immunoassays and enhance
      diffusional mixing in a microfluidic device.
AB  - Manufacturers of latex immunoassays have typically added surfactants to improve
      detection sensitivity and prevent non-specific aggregation of microspheres, which
      may cause both false positives and negatives during diagnostic testing. There is
      also growing interest in conducting immunoassays in smaller volumes using
      microfluidic devices with minimum human effort. The first goal of our study was
      to simplify immunoassays by eliminating the use of surfactants. Our second
      objective was to determine if this strategy would also enhance diffusional mixing
      in a microfluidic channel, which has been one of the biggest barriers to using
      these devices. We first ran a series of cuvette experiments to document the
      performance of sodium dodecyl sulfate (SDS) and polysorbate 80 (Tween 80)
      surfactants in a mouse immunoglobulin G (IgG) immunoassay using plain polystyrene
      microspheres. Next, we tested highly carboxylated microspheres with no
      surfactants, to determine if the same levels of accuracy and specificity could be
      achieved. Finally, we evaluated the surfactants and highly carboxylated
      microspheres in a microfluidic device. Our results show that highly carboxylated
      microspheres can indeed be used to replace surfactants and to induce rapid mixing
      via diffusion in a microfluidic device.

PMID- 16621473
TI  - An accurate quantitative analysis of polymorphs based on artificial neural
      networks.
AB  - Measurement precision based on homogeneous and accurate standard samples has been
      reported to result in significant improvement in the sensitivity and accuracy of
      the quantitative analysis of polymorphic mixtures. The purpose of this study was
      to further improve the accuracy of the quantitation based on data processing by
      artificial neural networks (ANNs), using such high quality standard samples.
      Homogeneous powder mixtures of alpha- and gamma-forms of indomethacin (IMC) at
      various ratios (0-50% alpha-form content) were subjected to X-ray powder
      diffractometry. The two diffraction peaks selected as the best combination in
      multiple linear regression (MLR) were used in the ANN with an extended Kalman
      filter as a training algorithm. The results obtained by ANN had better predictive
      accuracy at lower contents (0-5%) compared to those of MLR. ANNs for the
      diffraction data based on high quality standard samples provide an extremely
      precise and accurate quantification for polymorphic mixtures.

PMID- 16621474
TI  - Shear-flow induced detachment of Saccharomyces cerevisiae from stainless steel:
      influence of yeast and solid surface properties.
AB  - The present study focused on the shear-induced detachment of Saccharomyces
      cerevisiae in adhesive contact with a 316L stainless steel surface using a shear
      stress flow chamber, with a view to determining the respective influence of the
      yeast surface properties and the support characteristics. The effect of
      cultivation of S. cerevisiae yeast cells on their subsequent detachment from the
      solid surface was particularly investigated. In order to elucidate the role of
      stainless steel, non-metallic supports were used as control, covering a broad
      range of surface properties such as surface free energy and roughness:
      polypropylene (hydrophobic), polystyrene (mildly hydrophobic, similar to
      stainless steel) and glass (hydrophilic). All materials were very smooth with
      respect to the size of yeast. First, experiments were carried out on two types of
      yeast cells, just rehydrated in saline solution, a biological model widely used
      in the literature. The influence of the ionic strength (1.5 and 150 mM NaCl) on
      glass and stainless steel was evaluated. Unlike on glass, no clear evidence was
      found for electrostatic repulsion with stainless steel since high adhesion was
      observed whatever the ionic strength. A lack of correlation in adhesion results
      was also obtained when considering the surface physico-chemical characteristics
      of type I (hydrophilic) and type II (hydrophobic) rehydrated cells and those of
      both polymers. It was postulated that unavoidable "sticky" compounds were present
      on the cell wall, which could not be completely removed during the successive
      washings of the rehydrated cell suspension before use. This could dramatically
      alter the yeast surface properties and modify the adhesion strength, thus clearly
      demonstrating the necessity to work with yeast coming from fresh cultures.
      Biologically active yeast cells were then used. Once cultured, type I- and type
      II-yeast cells were shown to exhibit the same hydrophilic properties. Regardless
      of the material used, for the same ionic strength (150 mM NaCl), yeast adhesion
      was drastically reduced compared to rehydrated yeast cells. Among all the
      materials tested, the specificity of 316L stainless steel was clearly
      established. Indeed, for glass and polymers, cell adhesion was substratum
      dependent and driven by the balance between the Lifshitz-van der Waals and Lewis
      acid/base interactions. Despite nearly identical surface free energies for
      polystyrene and stainless steel, the metallic surface promoted a totally distinct
      behaviour which was characterized by a strong - although highly variable - yeast
      adhesion.

PMID- 16621475
TI  - Comblike poly(ethylene oxide)/hydrophobic C6 branched chitosan surfactant
      polymers as anti-infection surface modifying agents.
AB  - A series of structurally well-defined poly(ethylene oxide)/hydrophobic C6
      branched chitosan surfactant polymers that undergo surface induced self assembly
      on hydrophobic biomaterial surfaces were synthesized and characterized. The
      surfactant polymers consist of low molecular weight (Mw) chitosan backbone with
      hydrophilic poly(ethylene oxide) (PEO) and hydrophobic hexyl pendant groups.
      Chitosan was depolymerized by nitrous acid deaminative cleavage. Hexanal and
      aldehyde-terminated PEO chains were simultaneously attached to low Mw chitosan
      hydrochloride via reductive amination. The surfactant polymers were prepared with
      various ratios of the two side chains. The molecular composition of the
      surfactant polymers was determined by FT-IR and 1H NMR. Surface active properties
      at the air-water interface were determined by Langmuir film balance measurements.
      The surfactant polymers with PEO/hexyl ratios of 1:3.0 and 1:14.4 were used as
      surface modifying agents to investigate their anti-infection properties. E. coli
      adhesion on Silastic surface was decreased significantly by the surfactant
      polymer with PEO/hexyl 1:3.0. Surface growth of adherent E. coli was effectively
      suppressed by both tested surfactant polymers.

PMID- 16621476
TI  - Surface composition of dairy powders observed by X-ray photoelectron spectroscopy
      and effects on their rehydration properties.
AB  - The surface composition of three dairy powders was investigated by X-ray
      photoelectron spectroscopy. These spray-dried casein powders were more or less
      enriched in hygroscopic material (lactose and/or minerals). The principal
      limitation of these high protein content powders is their poor rehydration
      ability. Consequently, information about surface composition is required in order
      to get a better understanding of rehydration behaviour (i.e. wetting time and
      time of rehydration). The obtained results indicate that the surface of the three
      powders was dominated by proteins. Lactose and minerals are marginal compounds at
      the surface whereas the surface coverage of fat was over represented. A
      correlation between the lactose surface content and the wetting time of the
      powders was found, but no relationship with the surface fat. Moreover, as the
      surface is partly depleted in minerals and lactose, it is concluded that these
      compounds are principally located in the bulk of the particle. Therefore this
      observation could be related with a wetting time of the powders only slightly
      affected by the addition of hygroscopic material whereas the time of rehydration
      was strongly improved; powder wetting being more affected by the surface
      composition whereas powder dispersion being more influenced by the powder bulk
      composition.

PMID- 16621477
TI  - The electrochemical reaction mechanism of selenocystine on selenium-gold film
      modified glassy carbon electrode.
AB  - A simple and selective voltammetric method based on selenium-gold film modified
      glassy carbon electrode has been developed for investigating electrochemical
      reaction mechanism of selenocystine. With N2 saturated, redox reactions between
      selenocystine (SeC) and selenocysteine (SeCys) were judged to be two simple
      electron-transfer processes. With air saturated, the reduction reaction was
      diagnosed to be EC catalytic reaction (the chemical oxidation reaction of the
      SeCys by O2 (C) following the electron-transfer reaction (E)) and oxidation
      reaction is a simple electron-transfer process. With pure O2 saturated, only
      reduction peak was observed and the reaction was judged to be EC catalytic
      reaction. The electron-transfer numbers of redox reaction were calculated to be 2
      by chronocoulometry and rotating disk electrode.

PMID- 16621478
TI  - Formation of calcium phosphates in gelatin with a novel diffusion system.
AB  - The present paper demonstrated a novel and simple diffusion system to precipitate
      calcium phosphates in gelatin gel. In this system, a gelatin cup was specially
      used as the membrane separating reservoirs of calcium and phosphate ions.
      Relative to the conventional diffusion system, the novel one in our experiment
      decreased the time required for the deposition from 5-7 days to 20 h and
      increased the amount of the precipitated mineral phases significantly. The
      influence of pH values and concentrations of calcium and phosphate solutions
      buffered with Tris-HCl and NaOH, respectively, was investigated. The results
      showed that precipitation of the mineral phase at low pH values (7 for calcium
      and 11 for phosphate) and concentrations (200 mM for calcium and 15 mM for
      phosphate) resulted in the formation of plate-like octacalcium phosphate (OCP)
      crystals. With increasing the pH values of calcium and phosphate solutions to 8
      and 12, respectively, spherical amorphous calcium phosphate (ACP) particles were
      obtained uniquely. Furthermore, flower-like hydroxyapatite (HAP) aggregates
      composed of many nano-sized needles were formed from the solutions with high pH
      values (8 for calcium and 12 for phosphate) and concentrations (500 mM for
      calcium and 37.5 mM for phosphate). The novel diffusion system is proposed to
      play an important role in both studying the process of biological mineralization
      and synthesizing calcium phosphates in different forms.

PMID- 16621479
TI  - Oxaliplatin degradation in the presence of important biological sulphur
      containing compounds and plasma ultrafiltrate.
AB  - Oxaliplatin undergoes extensive non-enzymatic chemical transformation in the
      body. Complexes with sulphur-containing compounds have previously been found in
      plasma from patients treated with oxaliplatin. We have studied the kinetics for
      the reactions between oxaliplatin and cysteine, methionine, and glutathione, by
      determination of the degradation of oxaliplatin using liquid chromatography with
      UV-detection. We also studied the degradation of oxaliplatin in plasma
      ultrafiltrate (PUF). For the degradation of oxaliplatin in the presence of
      glutathione, methionine, and cysteine, the second-order rate constants were 4.7M(
      1)min(-1) (95% confidence interval [C.I.], 4.4-5.0M(-1)min(-1)), 5.5M(-1)min(-1)
      (95% C.I., 5.2-5.7M(-1)min(-1)), and 15M(-1)min(-1) (95% C.I., 14-17M(-1)min(
      1)), respectively. The reaction rate was much faster than previously reported
      kinetics for cisplatin. The degradation rate of oxaliplatin in PUF was biphasic.
      The rate constant for the first phase varied from 9.5x10(-3) to 0.13min(-1) and
      for the second phase from (1.7 to 1.8)x10(-3)min(-1) in PUF from five healthy
      volunteers. The first hours of the degradation of oxaliplatin in PUF are
      accounted for by the degradation of oxaliplatin in a cocktail of sodium chloride
      and sulphur-containing compounds at physiological plasma concentrations. In
      conclusion, the rate of the reaction of oxaliplatin with three sulphur-containing
      compounds was faster for oxaliplatin than what is previously known for cisplatin.
      This may be important with respect to differences in the cellular effects of
      cisplatin and oxaliplatin treatment.

PMID- 16621480
TI  - Frequency distribution of phenol sulfotransferase 1A1 activity in platelet cells
      from healthy Japanese subjects.
AB  - AIMS: To determine the distribution of sulfotransferase 1A1 (SULT1A1) activities,
      we used trans-4-hydroxytamoxifen (OHT) as a substrate to test samples from a
      Japanese population to examine whether the SULT1A1*2 allele can account for the
      wide distribution of OHT sulfating activity. We also studied genetic mutations
      other than the SULT1A1*2 allele to determine the cause of differences in SULT1A1
      protein expression and activity. METHODS: The subjects were 103 healthy Japanese
      adults. Identification of SULT1A1 genotypes was performed using a polymerase
      chain reaction-restriction fragment length polymorphism method. SULT1A1 activity
      in platelet cytosol was assayed using OHT as a substrate. SULT1A1 protein was
      detected using Western blotting analysis. Mutations other than SULT1A1*2 in the
      SULT1A1 gene were detected using sequencing analysis. RESULTS: SULT1A1*2 allele
      frequency was found to be 16.5%, while SULT1A1 activity ranged from 63 to
      1860pmol sulfated/h/mg platelet protein (260+/-241pmol sulfated/h/mg platelet
      protein, median+/-S.D.) using OHT as a substrate. The median values in subjects
      with SULT*1/*2 (221+/-113pmol sulfated/h/mg platelet protein, range 63-442, n=26)
      and SULT*2/*2 (124+/-66pmol sulfated/h/mg platelet protein, range 74-231, n=4)
      were significantly lower than that in subjects with SULT*1/*1 (303+/-267pmol
      sulfated/h/mg platelet protein, range 97-1859, n=73). A novel G148C mutation was
      found in one subject, who showed the lowest OHT sulfating activity, for a
      frequency of 0.49%. CONCLUSION: There was wide variety of OHT sulfating
      activities found among the present healthy Japanese subjects. The SULT1A1*2
      allele was found to be a common variant allele and was associated with decreased
      OHT sulfating activity. These observations may be related to inter-individual
      variations of OHT pharmacokinetics and the pharmacologic effects of tamoxifen
      seen in Japanese patients with breast cancer.

PMID- 16621481
TI  - Challenges of biological realism and validation in simulation-based medical
      education.
AB  - OVERVIEW: Simulation, both physical and computer-based, has a rich history in
      support of medical education. Essentially all these efforts have been aimed at
      instilling concrete measurable skills, akin to vocational training. They present
      learners with choices, facilitating a degree of learning by doing. The sets of
      learner choices are usually limited, with choices clearly classified into "right"
      and "wrong". But much of medicine is not much like a multiple-choice test. The
      realm of choices is broad and not always easily converted to a short list. The
      "correct" answer is not always known by the experienced physician beforehand,
      sometimes not even after the die is cast and the future unfolds. Computer
      simulation of human disease and its treatment can in principle be tremendously
      useful in the education of both basic and clinical scientists. This paper
      describes some challenges in the construction of simulation-based "liberal arts"
      biomedical education. OBJECTIVES: The educator attempting to develop a learning
      environment based on simulation of biology faces some special challenges. The
      challenges addressed in this paper are: face validity and deep validity; finding
      the right degree of realism; authoring biomedical models efficiently; managing
      randomness. To illustrate the issues, we trace the history of the Oncology
      Thinking Cap throughout several versions and expansions of educational
      objectives, and describe the detection and remediation of shortcomings related to
      these issues. DESIGN: Dealing effectively with issues of validity and realism can
      be accomplished if the acquisition of information driving and justifying the
      model development choices is documented, preferably automatically, during the
      process. Efficiency in authoring is greatly enhanced by judicious modularity to
      encourage re-use, and by the use of templated statements rather than raw code or
      exotic graphical components to represent the instructions driving the model.
      Randomness can be used to familiarize learners with the true relative proportions
      of types of cases, or to enrich the encountered cases with rarer but more
      instructive cases. When a learner repeats an encounter with a scenario while
      changing a single option, proper management of randomness is essential to avoid
      artifacts of random number generators. Otherwise an outcome change caused by a
      shift in random number streams may masquerade as an outcome change due to the
      changed option. CONCLUSION: Effective use of computer simulation of human disease
      and its treatment for biomedical education faces daunting obstacles, but these
      problems can be solved.

PMID- 16621482
TI  - Nano- and micro-particulate formulations of poorly water-soluble drugs by using a
      novel optimized technique.
AB  - A novel technique for the production of nano- and micro-particulate formulations
      of poorly water-soluble drugs has been developed. This technique involves the use
      of static mixer elements to provide fast precipitation by continuous turbulent
      mixing of two liquid flows, an aqueous phase and an organic phase, respectively.
      The objective of this study was to develop the mixer technique by investigating
      the influence of the element number on the particle size of the resulting
      dispersions. Four model active pharmaceutical ingredients (APIs) with a variety
      of polymers, lipids or surfactants underwent intensive mixing and the final
      suspensions showed a narrow size distribution. Parameters such as the flow rate
      and the temperature of the precipitated organic-aqueous phases were also
      significant in the reduction of particle size. Further development of the mixing
      technique led to reproducible and stable formulations with minimal excipient
      amounts. These formulations were spray- or freeze-dried to improve stability.

PMID- 16621483
TI  - Controlled release of cephalexin through gellan gum beads: effect of formulation
      parameters on entrapment efficiency, size, and drug release.
AB  - Gellan gum beads containing cephalexin were prepared by extruding the dispersion
      of cephalexin and gellan gum into a solution containing a mixture of calcium and
      zinc ions (counterions). Beads were prepared by changing experimental variables
      such as pH of the counterion solution and amount of cephalexin loading in order
      to optimize process variables on the final % drug entrapment efficiency, release
      rates, size, and morphology of the beads. Absence of chemical interactions
      between drug, anionic polymer, and counterions after production of beads was
      confirmed by Fourier transform infrared spectroscopy. Differential scanning
      calorimetry was used to understand the crystalline nature of the drug after its
      successful entrapment. These data indicated the amorphous dispersion of
      cephalexin in the polymer matrix. Beads were spherical in shape, with the average
      bead size ranging from 925 to 1183 microm as measured by the laser light
      scattering technique. Cephalexin entrapment of up to 69.24% was achieved. In
      vitro release studies were performed in 0.1 N HCl or pH 7.4 phosphate buffer and
      the release of cephalexin was achieved up to 6 h. Dynamic swelling studies were
      performed in 0.1 N HCl or pH 7.4 phosphate buffer. Diffusion coefficients were
      calculated for spherical geometry. The release data have been fitted to an
      empirical relation to estimate the transport parameters. Mathematical modeling
      studies were performed for spherical geometry by solving Fick's equation to
      compute concentration profiles. These results were correlated with the release
      profiles.

PMID- 16621484
TI  - Aqueous HPMCAS coatings: effects of formulation and processing parameters on drug
      release and mass transport mechanisms.
AB  - The major aim of the present work was to study the effects of various formulation
      and processing parameters on the resulting drug release kinetics from
      theophylline matrix pellets coated with aqueous hydroxypropyl methylcellulose
      acetate succinate (HPMCAS) dispersions. The plasticizer content, coating level
      and curing conditions significantly affected the release patterns in 0.1 M HCl,
      whereas no major effects were observed in phosphate buffer, pH 7.4. Due to the
      significant size of the HPMCAS particles (being in the micrometer range), their
      coalescence was particularly crucial and not complete upon coating. Consequently,
      at low coating levels continuous water-filled channels connected the bead cores
      with the release medium through which the drug could rapidly diffuse, resulting
      in high release rates even at low pH. In contrast, at high coating levels such
      continuous connections did not exist (due to the increased number of polymer
      particle layers), and drug release was controlled by diffusion through the
      macromolecular network resulting in much lower release rates in 0.1 M HCl.
      Importantly, pellet curing at elevated temperature and ambient relative humidity
      or exposure to elevated relative humidity at room temperature did not
      significantly alter the microstructure of the coatings, leading to only slightly
      decreased drug release rates. In contrast, pellet curing at elevated temperature
      combined with elevated relative humidity induced significant further polymer
      particle coalescence, resulting in a change of the underlying drug release
      mechanism and significantly reduced drug release rates.

PMID- 16621485
TI  - Modification of the tri-phasic drug release pattern of leuprolide acetate-loaded
      poly(lactide-co-glycolide) microparticles.
AB  - Leuprolide acetate-loaded poly(lactide-co-glycolide) (PLGA RG503H) microparticles
      prepared by the solvent evaporation method had a tri-phasic drug release pattern
      over a duration of up to 2 months. An initial release was followed by a slow drug
      release phase and a final rapid drug release. The objective of this study was to
      identify parameters, which shift the release profile from the tri-phasic to a
      more continuous release profile. Varying formulation and processing parameters
      (e.g., drug loading, volume of the external aqueous phase, using low molecular
      weight PLGA, different microparticle drying methods) affected the initial release
      (burst) but did not influence the drug release thereafter. The addition of the
      hydrophilic polymer polyvinylpyrrolidone (PVP) led to the formation of more
      porous microparticles. This influenced the initial release but did not change the
      tri-phasic drug release pattern. The inclusion of medium chain triglycerides
      (MCT) successfully shifted the tri-phasic pattern to a continuous release
      profile. MCT accelerated the leuprolide release in the second, slow release phase
      and reduced it in the final rapid release phase. MCT led to the formation of
      microparticles with an irregular surface and a highly porous inner structure.
      Differential scanning calorimetry (DSC) revealed a high encapsulation efficiency
      of MCT (88-105%) in the microparticles and an unchanged glass transition
      temperature (Tg) of PLGA.

PMID- 16621486
TI  - Release and diffusional modeling of metronidazole lipid matrices.
AB  - In this study, the first aim was to investigate the swelling and relaxation
      properties of lipid matrix on diffusional exponent (n). The second aim was to
      determine the desired release profile of metronidazole lipid matrix tablets. We
      prepared metronidazole lipid matrix granules using Carnauba wax, Beeswax, Stearic
      acid, Cutina HR, Precirol ATO 5, and Compritol ATO 888 by hot fusion method and
      pressed the tablets of these granules. In vitro release test was performed using
      a standard USP dissolution apparatus I (basket method) with a stirring rate of
      100 rpm at 37 degrees C in 900 ml of 0.1 N hydrochloric acid, adjusted to pH 1.2,
      as medium for the formulations' screening. Hardness, diameter-height ratio,
      friability, and swelling ratio were determined. Target release profile of
      metronidazole was also drawn. Stearic acid showed the highest and Carnauba wax
      showed the lowest release rates in all formulations used. Swelling ratios were
      calculated after the dissolution of tablets as 9.24%, 6.03%, 1.74%, and 1.07% for
      Cutina HR, Beeswax, Precirol ATO 5, and Compritol ATO 888, respectively. There
      was erosion in Stearic acid, but neither erosion nor swelling in Carnauba wax,
      was detected. According to the power law analysis, the diffusion mechanism was
      expressed as pure Fickian for Stearic acid and Carnauba wax and the coupling of
      Fickian and relaxation contributions for other Cutina HR, Beeswax, Compritol ATO
      888, and Precirol ATO 5 tablets. It was found that Beeswax (kd=2.13) has a very
      close drug release rate with the target profile (kt=1.95). Our results suggested
      that swelling and relaxation properties of lipid matrices should be examined
      together for a correct evaluation on drug diffusion mechanism of insoluble
      matrices.

PMID- 16621487
TI  - Physical stability, centrifugation tests, and entrapment efficiency studies of
      carnauba wax-decyl oleate nanoparticles used for the dispersion of inorganic
      sunscreens in aqueous media.
AB  - Aqueous nanoscale lipid dispersions consisting of carnauba wax-decyl oleate
      mixtures acting as carriers or accompanying vehicles for inorganic sunscreens
      such as barium sulfate, strontium carbonate, and titanium dioxide were prepared
      by high pressure homogenization. For the manufacture of these nanosuspensions,
      three pigment concentrations (%wt), namely 2, 4, and 6, and two carnauba wax
      decyl oleate ratios, 1:1 and 2:1, were used, being some of these combinations
      chosen for stability studies. Six-month physical stability tests at 4, 20, and 40
      degrees C selecting the mean particle size and the polydispersity index of the
      nanosuspensions as reference parameters were performed. Centrifugation tests of
      the nanosuspensions assessed by transmission electron microscopy and by the
      determination of the content of pigments and carnauba wax in the separated
      fractions were done. The mean particle sizes and the polydispersity indices of
      the nanosuspensions were not altered after six-month storages at 20 and at 40
      degrees C. However, the storage of those at 4 degrees C considerably increased
      the particle size and polydispersity of the systems, particularly when wax-oil
      ratios (2:1) were used for the entrapment of the pigments. Transmission electron
      micrographs of centrifuged samples denoted the presence of three major fractions
      showing the different types of particles integrated into the nanosuspensions.
      Furthermore, it was observed that not all the carnauba wax participated in the
      entrapment of the pigment. Regarding the amount of pigment being encapsulated or
      bonded by the wax-oil matrices, entrapment efficiencies higher than 85.52% were
      reported.

PMID- 16621488
TI  - Liquid crystalline phases of monoolein and water for topical delivery of
      cyclosporin A: characterization and study of in vitro and in vivo delivery.
AB  - Reverse cubic and hexagonal phases of monoolein have been studied as drug
      delivery systems. The present study was aimed at investigating whether these
      systems enhance the cutaneous penetration of cyclosporin A (CysA) in vitro (using
      porcine ear skin) and in vivo (using hairless mice). Different mesophases were
      obtained depending on CysA concentration. CysA at 4% allowed the formation of
      reverse cubic and hexagonal phases in a temperature range of 25-40 degrees C. At
      8%, CysA induced the formation of other phases, which might be due to an
      interaction between the polar groups of the peptide and monoolein. In vitro, the
      cubic phase increased the penetration of CysA in the stratum corneum (SC) and
      epidermis plus dermis ([E+D]) at 12 h post-application. The reverse hexagonal
      phase increased CysA penetration in [E+D] at 6 h and percutaneous delivery at 7.5
      h post-application. In vivo, both liquid crystalline phases increased CysA skin
      penetration. Topical application of these systems, though, induced skin
      irritation after a 3-day exposure. These results demonstrate that liquid
      crystalline systems of monoolein are effective in optimizing the delivery of
      peptides to the skin. The skin irritation observed after topical application of
      cubic and hexagonal phases should be minimized for their safe use as topical
      delivery systems.

PMID- 16621489
TI  - Quantitative measurements of localized density variations in cylindrical tablets
      using X-ray microtomography.
AB  - Direct compaction is a complex process that results in a density distribution
      inside the tablets which is often heterogeneous. Therefore, the density
      variations may affect the compact properties. A quantitative analysis of this
      phenomenon is still lacking. Recently, X-ray microtomography has been
      successfully used in pharmaceutical development to study qualitatively the impact
      of tablet shape and break-line in the density of pharmaceutical tablets. In this
      study, we evaluate the density profile in microcrystalline cellulose (Vivapur 12)
      compacts obtained at different mean porosity (ranging from 7.7% to 33.5%) using X
      ray tomography technique. First, the validity of the Beer-Lambert law is studied.
      Then, density calibration is performed and density maps of cylindrical tablets
      are obtained and visualized using a process with colour-scale calibration plot
      which is explained. As expected, important heterogeneity in density is observed
      and quantified. The higher densities in peripheral region were particularly
      investigated and appraised in regard to the lower densities observed in the
      middle of the tablet. The results also underlined that in the case of
      pharmaceutical tablets, it is important to differentiate the mechanical
      properties representative of the total volume tablet and the mechanical
      properties that only characterize the tablet surface like the Brinell hardness
      measurements.

PMID- 16621490
TI  - Investigation of nanocapsules stabilization by amorphous excipients during freeze
      drying and storage.
AB  - Freeze-drying was recently applied to improve the long-term storage stability of
      nanoparticles. Nanocapsules have a thin polymeric envelope that may not withstand
      the stresses of such process. So, cryoprotectants and lyoprotectants are usually
      added to the formulation to protect these vectors during freezing and desiccation
      steps. The aim of this paper was to investigate the importance of the
      vitrification of cryoprotectants on the stabilization of nanocapsules during
      freezing, desiccation, and storage steps. Furthermore, the effect of stabilizer
      crystallization on the conservation of nanocapsules properties was studied.
      Finally, the effect of temperature storage and relative humidity on the stability
      of nanocapsules was tested through an accelerated stability study. Results
      indicate that nanocapsules stabilization during the different steps of freeze
      drying requires their dispersion within a vitrified matrix of amorphous excipient
      to protect them against the stress of freezing and dehydration. The
      crystallization of this stabilizer during the freezing, the desiccation or the
      storage steps can destabilize these fragile particles. Electron spectroscopy for
      chemical analysis revealed the adsorption of nanocapsules at the interface
      ice/liquid during the freezing step. Such adsorption must be avoided in the case
      of freeze-drying of immuno-nanoparticles to preserve the native structure of
      proteins attached to their surface.

PMID- 16621491
TI  - Cryopreserved human hepatocytes in suspension are a convenient high throughput
      tool for the prediction of metabolic clearance.
AB  - Hepatocyte assays, routinely used to assess the metabolic stability of new
      chemical entities, were recently improved by using hepatocytes in suspension
      instead of primary cultures [N. Blanchard, L. Richert, B. Notter, F. Delobel, P.
      David, P. Coassolo, T. Lave, Impact of serum on clearance predictions obtained
      from suspensions and primary cultures of rat hepatocytes, Eur. J. Pharm. Sci. 23
      (2004) 189-199]. The aim of the present study was to investigate miniaturising
      the suspension assay by using cryopreserved human hepatocytes, i.e., 150,000
      cells/well in 96-well plates, to predict hepatic clearance (CLH) in order to
      increase compound throughput and decrease cost and tissue requirements. For this,
      an evaluation was first carried out with rat hepatocytes. Then, human hepatocytes
      from various donors were used under these predetermined conditions, either
      immediately after isolation, either after a 20-h-cold storage period in UW or
      after cryopreservation. The values of CLint and CLH determined using human
      hepatocytes in suspension in 96-well plates, immediately after isolation, after
      cold storage or after cryopreservation, were comparable to those obtained with
      hepatocytes in primary culture. In particular, the use of cryopreserved human
      hepatocytes in suspension in a 96-well format appeared to be largely satisfactory
      as a tool for screening and ranking of compounds in the early phase of the drug
      discovery process.

PMID- 16621492
TI  - Peroxidase secretion in rat submandibular glands induced by PGE2: role of cAMP
      and nitric oxide.
AB  - Free radicals are associated with the appearance of disorders such as tumours,
      CNS alterations and inflammatory pathologies. Their levels are known to be
      increased in inflammatory diseases due to the activity of prostaglandins, which
      are related to protein secretion including enzymes. Peroxidase is an oral enzyme
      that is implicated in the defence of the oral cavity. In this paper,
      investigations of the effect and mechanism of the activity of prostaglandin E2
      (PGE2) on peroxidase secretion of female rat submandibular glands are reported.
      Results showed that PGE2 significantly increased the secretion of submandibular
      peroxidase and that this effect was mediated by an increase of intracellular cAMP
      and nitric oxide synthase activation. This could imply that prostaglandins play a
      modulatory role in diseases where free radicals are involved.

PMID- 16621493
TI  - Elevated prostaglandin E2 level via cPLA2--COX-2--mPGES-1 pathway involved in
      bladder carcinogenesis induced by terephthalic acid-calculi in Wistar rats.
AB  - To investigate the prostaglandin E2 (PGE2) biosynthetic mechanism in bladder
      carcinogenesis, we established Wistar rat model of bladder papilloma and
      transitional cell carcinoma (TCC) induced by 5% terephthalic acid (TPA)
      treatment. Then, the mRNA level of cytosolic phospholipase A2 (cPLA2),
      cyclooxygenases (COX)-1 and -2, membrane-bound PGE2 synthases (mPGES)-1 and -2
      was detected using reverse transcription polymerase chain reaction (RT-PCR).
      Immunoblotting was applied to detect the expression of COX-2 protein.
      Proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry.
      In addition, the level of PGE2 was measured by radioimmunoassay (RIA). Bladder
      papilloma (100%, 8/8) was examined in rats after 24-week treatment, and bladder
      TCC (80%, 16/20) was found after 48-week treatment. Histopathological changes
      were not found in control group rats. The incidence of bladder papilloma and TCC
      in test group was significantly higher than that in control group (P<0.01). The
      mRNA levels of cPLA2, COX-2 and mPGES-1 in the bladder papilloma and TCC were
      significantly higher than those in normal bladder (P<0.01), while the mRNA levels
      of COX-1 and mPGES-2 in TCC were unchanged compared with normal bladder. Bladder
      TCC exhibited a substantial expression of COX-2 protein. On the contrary, normal
      bladder tissue barely expresses COX-2 protein. PCNA labeling index (LI) and the
      level of PGE2 in bladder papilloma are much higher than those in normal bladder
      (P<0.01), but lower than those in bladder TCC (P<0.05). In conclusion, increasing
      PGE2 level via cPLA2--COX-2--mPGES-1 pathway may play an important role in rat
      bladder carcinogenesis. PGE2 may be a biomarker for the development of bladder
      TCC. cPLA2 and mPGES-1 may be targets for development of novel chemoprevention
      strategies for bladder TCC.

PMID- 16621494
TI  - Two new Fusicoccum species from Acacia and Eucalyptus in Venezuela, based on
      morphology and DNA sequence data.
AB  - Botryosphaeria spp. are common endophytes of woody plants, and they also include
      some serious pathogens of Eucalyptus and Acacia species. Numerous anamorphs have
      been associated with Botryosphaeria, of which the species Fusicoccum are amongst
      the most common. Here, we characterize two new Fusicoccum species, isolated from
      Eucalyptus and Acacia trees in Venezuela, based on morphological features in
      culture and comparisons of DNA sequence data. The two taxa named Fusicoccum
      andinum and F. stromaticum spp. nov, reside in two well-supported clades (BS
      values = 100%) based on a combined data set of the ITS of the rDNA operon and
      translation elongation factor 1-alpha (EF1- alpha) gene sequences. The conidia of
      F. andinum are unusually large amongst Botryosphaeria anamorphs, and peripherally
      resemble those of B. mamane and B. melanops. F. stromaticum is characterized by
      large conidiomata in cultures, growth at 35 degrees C and slightly thickened
      conidial walls, which is different to most other Fusicoccum spp. No teleomorphs
      were observed for these fungi, but DNA sequence data show that they are anamorphs
      of Botryosphaeria.

PMID- 16621495
TI  - Molecular data place Trypetheliaceae in Dothideomycetes.
AB  - The phylogenetic position of Trypetheliaceae was studied using partial sequences
      of the mtSSU and nuLSU rDNA of 100 and 110 ascomycetes, respectively, including
      48 newly obtained sequences. Our analysis confirms Trypetheliaceae as
      monophyletic and places the family in Dothideomycetes. Pyrenulaceae, which were
      previously classified with Trypetheliaceae in Pyrenulales or Melanommatales, are
      supported as belonging to Chaetothyriomycetes. Monophyly of Pyrenulales,
      including Trypetheliaceae is rejected using three independent test methods.
      Monophyly of Arthopyreniaceae plus Trypetheliaceae, the two families including
      lichen-forming fungi in Dothideomycetes, is also rejected, as well as a placement
      of Trypetheliaceae in Pleosporales (incl. Melanommatales).

PMID- 16621496
TI  - Trichoderma theobromicola and T. paucisporum: two new species isolated from cacao
      in South America.
AB  - Trichoderma theobromicola and T. paucisporum spp. nov. are described. Trichoderma
      theobromicola was isolated as an endophyte from the trunk of a healthy cacao tree
      (Theobroma cacao, Malvaceae) in Amazonian Peru; it sporulates profusely on common
      mycological media. Trichoderma paucisporum is represented by two cultures that
      were obtained in Ecuador from cacao pods partially infected with frosty pod rot,
      Moniliophthora roreri; it sporulates sporadically and most cultures remain
      sterile on common media and autoclaved rice. It sporulates more reliably on
      synthetic low-nutrient agar (SNA) but produces few conidia. Trichoderma
      theobromicola was reintroduced into cacao seedlings through shoot inoculation and
      was recovered from stems but not from leaves, indicating that it is an endophytic
      species. Both produced a volatile/diffusable antibiotic that inhibited
      development of M. roreri in vitro and on-pod trials. Neither species demonstrated
      significant direct in vitro mycoparasitic activity against M. roreri.

PMID- 16621498
TI  - The road much traveled: trafficking in the cell nucleus.
AB  - Trafficking of RNA molecules and proteins within the cell nucleus is central to
      genome function. Recent work has revealed the nature of RNA and protein motion
      within the nucleus and across the nuclear membrane. These studies have given
      insight into how molecules find their destinations within the nucleus and have
      uncovered some of the structural properties of the nuclear microenvironment.
      Control of RNA and protein trafficking is now emerging as a physiological
      regulatory mechanism in gene expression and nuclear function.

PMID- 16621499
TI  - A probe for NADH and H2O2 amperometric detection at low applied potential for
      oxidase and dehydrogenase based biosensor applications.
AB  - Modified screen-printed electrodes for amperometric detection of H(2)O(2) and
      nicotinamide adenine dinucleotide (NADH) at low applied potential are presented
      in this paper. The sensors are obtained by modifying the working electrode
      surface with Prussian Blue, a well known electrochemical mediator for H(2)O(2)
      reduction. The coupling of this sensor with phenazine methosulfate (PMS) in the
      working solution gives the possibility of measuring both NAD(P)H and H(2)O(2).
      PMS reacts with NADH producing PMSH, which in the presence of oxygen, gives an
      equimolar amount of H(2)O(2). This allows the measurement of both analytes with
      similar sensitivity (357 mA mol(-1)L cm(-2) for H(2)O(2) and 336 mA mol(-1)L cm(
      2) for NADH) and LOD (5x10(-7)mol L(-1) for H(2)O(2) and NADH) and opens the
      possibility of a whole series of biosensor applications. In this paper, results
      obtained with a variety of dehydrogenase enzymes (alcohol, malic, lactate,
      glucose, glycerol and glutamate) for the detection of enzymatic substrates or
      enzymatic activity are presented demonstrating the suitability of the proposed
      method for future biosensor applications.

PMID- 16621500
TI  - Sensing minute changes in biological cell monolayers with THz differential time
      domain spectroscopy.
AB  - We used terahertz differential time-domain spectroscopy (THz-DTDS) to measure
      minute changes of bovine lung microvessel endothelial cells (BLMVEC) in response
      to vascular endothelial growth factor (VEGF). These changes were reflected by
      alterations in THz wave attenuations and THz dielectric properties of the treated
      cells. The VEGF-induced THz attenuations of cell monolayers correlated well with
      changes in transendothelial resistance, as measured using electric cell-substrate
      impedance sensing (ECIS). However, the morphological differences that gave rise
      to these changes were not observed with standard optical phase contrast
      microscopy. We conclude that THz-DTDS is a highly sensitive, non-invasive,
      powerful new tool to measure minute changes in the morphology of live, cultured
      cell monolayers. This method enables spectroscopic investigations of cells in the
      THz band, providing information unavailable through other conventional methods
      such as optical phase contrast microscopy and ECIS.

PMID- 16621501
TI  - Quartz crystal microbalance for the determination of daminozide using molecularly
      imprinted polymers as recognition element.
AB  - As the daminozide (DM) and its metabolite have been identified to be potentially
      carcinogenic, rapid detection method for them is necessary for food safety. A
      type of piezoelectric crystal sensor has been prepared by using a molecularly
      imprinted polymer (MIP) as recognition element. The molecularly imprinted polymer
      was prepared by hot-induced precipitation polymerization, and then the polymer
      particles were fixed on the surface of the electrode. Scanning electron
      microscopy (SEM) and atomic force microscopy (AFM) were employed to evaluate the
      obtained imprinted polymer particles and the MIP sensitive film coated on the
      electrode. The results showed that a typical time-response curve of the MIP
      coated crystal to the DM solution had been given, frequency shifts versus
      logarithm changes of DM showed good linear correlation within the concentration
      range of 1.0x10(-9) to 10(-6) mg/mL (y=11.38 lg x+115.45, r=0.9872) and 1.0x10(
      6) to 10(-1) mg/mL (y=25.22lgx+209.44, r=0.9938), respectively. The detection
      limit was 5.0x10(-8) mg/mL (S/N=3), which is lower than that of conventional
      methods. Further, computer simulation technology was employed to investigate the
      interaction between methacrylic acid and DM for elucidating the recognition
      mechanism. The influencing factor pH has also been investigated. The injection
      experiments of DM structurally related compounds indicated that the obtained
      sensor has high sensitivity, excellent selectivity, low cost, good
      reproducibility, and reusable property by combining with piezoelectric crystal
      and molecularly imprinted polymer.

PMID- 16621502
TI  - A sequential injection analysis/chemiluminescent plant tissue-based biosensor
      system for the determination of diamine.
AB  - In this paper, a new chemiluminescent plant tissue-based biosensor for diamine
      detection was presented by employing sequential injection analysis (SIA), which
      facilitates precise fluidic handling and lower consumption of sample and
      reagents. Pea-seedling tissue acted as the molecular recognition element and was
      packed in a mini-PTFE column and further incorporated in the SIA system. The
      analysis of diamines, such as putrescine and cadaverine, is based on an enzymatic
      conversion which takes place in the plant tissue column to produce hydrogen
      peroxide. The formed hydrogen peroxide was detected by a chemiluminescence
      reaction involving luminol and Co(2+). Under the optimal conditions, the linear
      calibration graphs were obtained within 0.2-80 microM (putrescine) and 0.5-100
      microM (cadaverine). The detection limits of 0.03 and 0.06 microM were achieved
      for putrescine and cadaverine, respectively, along with the relative standard
      deviations of 2.14% and 3.08% (n=11) and a sampling frequency of 40 h(-1). The
      present biosensor has been used for the analysis of diamine in fish samples with
      an acceptable accuracy.

PMID- 16621503
TI  - Multiple detection of food-borne pathogenic bacteria using a novel 16S rDNA-based
      oligonucleotide signature chip.
AB  - There have been many attempts to develop sensitive and accurate techniques for
      the detection and diagnosis of pathogenic bacteria using nucleic acid-based
      technology. To achieve efficient multiple detection of seven selected food-borne
      pathogens, we assessed the respective 16S rDNA pathogen specific sequences using
      an oligonucleotide-based signature array. Strategic optimal design of specific
      capture probes was achieved by using the characteristic first variable region. To
      assess the specificity of this pathogen detection system, we employed a two-step
      experimental strategy. Under conditions established through experiments with
      chemically synthesized model targets comprising both conserved and variable
      regions of 16S rDNA, we confirmed the validity of this system using real 16S rDNA
      targets. Detection with real targets was successfully performed using our system,
      and better specificity was obtained compared to experiments with model targets.
      Moreover, the subtypes of Vibrio pathogens were successfully classified. We
      developed a two-dimensional visualization plot tool for positive control and
      specific spots, which allowed facile and minute differentiation between spot
      intensities. Repeated array formats were employed to ensure experimental
      uniformity, and included the statistical p-value criterion for pathogen
      discrimination. The present results thus indicate that our novel oligonucleotide
      based signature chip detection system can be employed for the effective detection
      of multiple pathogens.

PMID- 16621504
TI  - Embryonic stem cells as a novel cell source of cell-based biosensors.
AB  - To investigate the use of embryonic stem cells as biosensor elements, mouse
      embryoid bodies were cultured on the surface of the light-addressable
      potentiometric sensor and induce to in vitro differentiate into cardiomyocytes
      and neurons. Extracellular potentials of the cells were recorded by sensor, to
      detect stem cells potential applications in drugs screening. The experimental
      results show that known cardiac stimulants (isoproterenol) and relaxants
      (carbamylcholine) have characteristic effects on the cardiomyocytes in terms of
      the changes of beat frequency, amplitude and duration. Thus, the embryonic stem
      cells potentially represent a renewable cell source for the cell-based
      biosensors.

PMID- 16621505
TI  - Direct electrochemistry of hemoglobin in PHEA and its catalysis to H2O2.
AB  - Hemoglobin (Hb) was immobilized on glassy carbon (GC) electrode by a kind of
      synthetic water-soluble polymer, poly-alpha,beta-[N-(2-hydroxyethyl)-L
      aspartamide] (PHEA). A pair of well-defined and quasi-reversible cyclic
      voltammetric peaks was achieved, which reflected the direct electron-transfer of
      the Fe(III)/Fe(II) couple of Hb. The formal potential (E degrees'), the apparent
      coverage (Gamma(*)) and the electron-transfer rate constant (k(s)) were
      calculated by integrating cyclic voltammograms experimental data. Scanning
      electron microscopy (SEM) demonstrated the morphology of Hb-PHEA film very
      different from the Hb and PHEA films. Ultraviolet visible (UV-vis) spectroscopy
      showed Hb in PHEA film remained its secondary structure similar to the native
      state. In respect that the immobilized protein remained its biocatalytic activity
      to the reduction of hydrogen peroxide (H(2)O(2)), a kind of mediator-free
      biosensor for H(2)O(2) could be developed. The apparent Michaelis-Menten constant
      (K(m)(app)) was estimated to be 18.05 microM. The biosensor exhibited rapid
      electrochemical response and good stability. Furthermore, uric acid (UA),
      ascorbic acid (AA) and dopamine (DA) had little interferences with the
      amperometric signal of H(2)O(2), which provide the perspective of this H(2)O(2)
      sensor to be used in biological environments.

PMID- 16621506
TI  - The SPR signal in living cells reflects changes other than the area of adhesion
      and the formation of cell constructions.
AB  - Surface plasmon resonance (SPR) sensors detected large angle of resonance (AR)
      changes, when RBL-2H3 rat mast cells were cultured and activated on a sensor
      chip. Here, we demonstrated that PAM212 mouse keratinocytes also showed a large
      change in AR, when EGF-stimulated. We explored these changes due to intracellular
      reactions, through the relationship between the AR and the area of cell adhesion,
      using confocal microscopy for RBL-2H3 cells and PAM212 cells. The effect of
      Mycalolide B and Toxin B, inhibitors for cell motility, on AR was observed using
      RBL-2H3 cells. Measuring AR in the presence of various numbers of non-stimulated
      cells demonstrated that AR and cell density were proportional. However, the AR
      increase in response to antigen was 35% higher than that expected by solely an
      increase of the cell adhesion area. Moreover, the AR with PAM212 cells decreased
      following a transient increase in response to EGF, whilst the area of cell
      adhesion remained at an increased level. Furthermore, the treatment of RBL-2H3
      cells with either Mycalolide B or Toxin B slightly inhibited, but never abolished
      the AR increase induced by antigen. These treatments abolished all morphological
      changes, including ruffling and the increase of cell adhesion area observed by
      light microscopy. These results suggest that AR changes reflect intracellular
      events rather than changes in the size of the area to which cells adhere.

PMID- 16621507
TI  - Protein and cell micropatterning and its integration with micro/nanoparticles
      assembly.
AB  - Micropatterning of proteins and cells has become very popular over the past
      decade due to its importance in the development of biosensors, microarrays,
      tissue engineering and cellular studies. This article reviews the techniques
      developed for protein and cell micropatterning and its biomedical applications.
      The prospect of integrating micro and nanoparticles with protein and cell
      micropatterning is discussed. The micro/nanoparticles are assembled into patterns
      and form the substrate for proteins and cell attachment. The assembled particles
      create a micro or nanotopography, depending on the size of the particles
      employed. The nonplanar structure can increase the surface area for biomolecules
      attachment and therefore enhance the sensitivity for detection in biosensors.
      Furthermore, a nanostructured substrate can influence the conformation and
      functionality of protein attached to it, while cellular response in terms of
      morphology, adhesion, proliferation, differentiation, etc. can be affected by a
      surface expressing micro or nanoscale structures. Proteins and cells tend to lose
      their normal functions upon attachment to substrate. By recognizing the types of
      topography that are favourable for preserving proteins and cell behaviour, and
      integrating it with micropattering will lead to the development of functional
      protein and cell patterns.

PMID- 16621508
TI  - DNA immobilisation procedures for surface plasmon resonance imaging (SPRI) based
      microarray systems.
AB  - Two different surface chemistries have been studied for the development of
      surface plasmon resonance imaging (SPRI) based DNA microarray affinity sensors:
      (1) 11-mercaptoundecanoic acid-poly(ethylenimine) (MUA-PEI) and (2) dextran
      procedures. The MUA-PEI method consists of assembling a multilayer on the basis
      of electrostatic interactions formed with: 11-mercaptoundecanoic acid (MUA),
      poly(ethylenimine) (PEI) and extravidin layers. The dextran procedure involves
      assembling a multilayer formed with 11-mercaptoundecanol, dextran and
      streptavidin layers, which are linked by covalent bonds. The oligonucleotide
      probes are immobilised onto the sensor surface as spots forming a matrix 14x14,
      which is spotted by a robot, while the target sequences are free in solution. The
      system allows the interaction (hybridisation) monitoring, in real-time and in
      parallel, of unlabeled oligonucleotide solution targets to oligonucleotide probes
      immobilised on a 196 spots matrix. Using oligonucleotides as probes and targets,
      both functionalised surfaces have been evaluated in view of their application to
      the diagnosis of gene mutations involved in human diseases. In particular, we
      demonstrate the ability to detect, in parallel, several mutations causing human
      cystic fibrosis (CF), which lie within exon 10 of the human cystic fibrosis
      transmembrane conductance regulator (CFTR) gene. The immobilised probes were
      complementary to sequences corresponding the mutant or wild type alleles. Two
      deletions of three bases (DeltaF508 and DeltaI507) and four single nucleotide
      polymorphisms (M470V, Q493X, V520F and 1716 G>A) were investigated. In both
      functionalised surfaces, the system showed the capacity to discriminate normal
      and mutant sequences differing by a single base.

PMID- 16621509
TI  - Highly selective and sensitive determination of dopamine using a Nafion/carbon
      nanotubes coated poly(3-methylthiophene) modified electrode.
AB  - A poly(3-methylthiophene) modified glassy carbon electrode coated with
      Nafion/single-walled carbon nanotubes film was fabricated and used for highly
      selective and sensitive determination of dopamine. The hybrid film surface of the
      modified electrode was characterized by scanning electrochemical microscopy
      (SECM) and the results indicated that the carbon nanotubes were dispersed
      uniformly on the conductive polymer. The experimental results suggest that the
      hybrid film modified electrode combining the advantages of poly(3
      methylthiophene), carbon nanotubes with Nafion exhibits dramatic electrocatalytic
      effect on the oxidation of dopamine (DA) and results in a marked enhancement of
      the current response. In 0.1M phosphate buffer solution (PBS) of pH 7.0, the
      differential pulse voltammetric (DPV) peak heights are linear with DA
      concentration in three intervals, viz. 0.020-0.10 microM, 0.10-1.0 microM and 1.0
      6.0 microM, with correlation coefficients of 0.9993, 0.9996 and 0.9993,
      respectively. The detection limit of 5.0 nM DA could be estimated (S/N=3).
      Moreover, the interferences of ascorbic acid (AA) and uric acid (UC) are
      effectively diminished. This hybrid film modified electrode can be applied to the
      determination of DA contents in dopamine hydrochloride injection and human serum.
      These attractive features provide a potential application for either in vitro
      measurement of DA in the presence of excess AA and UA or as detectors in flow
      injection analysis (FIA) and high performance liquid chromatography (HPLC).

PMID- 16621510
TI  - Amperometric biosensor based on tyrosinase immobilized on a boron-doped diamond
      electrode.
AB  - A novel method has been developed to immobilize tyrosinase onto the surface of
      boron-doped diamond (BDD) electrode. The hydrogen-terminated BDD (HBDD) surface
      was first functionalized by photochemically linking vinyl groups of allylamine,
      producing covalently linked amine-terminated active BDD (ABDD) surface. Then the
      tyrosinase was immobilized onto the ABDD surface by carbodiimide coupling
      reaction. The amperometric response was measured as a function of concentration
      of phenolic compounds in 0.1M phosphate buffer solution (pH 6.5). The tyrosinase
      modified ABDD electrode gave a linear response range of 1-175, 1-200 and 1-200
      microM and sensitivity of 80.0, 181.4 and 110.0 mA M(-1)cm(-2) for phenol, p
      cresol, 4-chlorophenol, respectively. Moreover, selective detection of dopamine
      (DA) in the presence of ascorbic acid (AA) has been demonstrated with the
      tyrosinase-modified ABDD electrode. Linearity was observed within the range of 5
      120 microM. The above enzyme electrode could maintain 90% of its original
      activity after intermittent use for 1 month when storing in a dry state at 4
      degrees C.

PMID- 16621511
TI  - Electrochemiluminescent hybridization chip with electric field aided mismatch
      discrimination.
AB  - This paper describes a heterogeneous DNA-hybridization assay based on
      electrochemiluminescence (ECL) detection on gold electrodes. Short, 15-mer
      oligonucleotides were conjugated with a synthesized electrochemiluminescent
      label, bis(2,2'-bipyridine)-5-isothiocyanato-1,10-phenanthroline ruthenium(II) at
      the amino-modified 5'-end. Gold electrodes were derivatized with 15-mer
      oligonucleotide probes via 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide
      hydrochloride (EDC)/N-hydroxysuccinimide (NHS) cross-linking reaction and
      hybridized with Ru-labeled strands. Two types of self-assembled-monolayers have
      been utilized for the immobilization reaction, 3-mercaptopropanoic acid (3-MHA)
      and 16-mercaptohexadecanoic acid (16-MHA). Longer thiols were more stable at high
      electrode potentials needed for the ECL generation. The system was sensitive down
      to 1 fmol of labeled complementary strand, detected in 30 microL of buffer.
      Mismatch discrimination was achieved both passively by washing and actively by
      application of negative electrode potential on electrodes prior to detection, but
      active denaturing lead to better results. Two base-pair mismatches were
      discriminated at room temperature.

PMID- 16621512
TI  - Rice Cluster I methanogens, an important group of Archaea producing greenhouse
      gas in soil.
AB  - Methane, which is an important greenhouse gas, is to a large part produced by
      methanogenic archaea in anoxic soils and sediments. Rice Cluster I methanogens
      have been characterized on the basis of their 16S rRNA and mcrA gene sequences,
      and were found to form a separate lineage within the phylogenetic radiation of
      Methanosarcinales and Methanomicrobiales. As isolation has not been achieved
      until recently, our knowledge of distribution, physiology and environmental
      significance of Rice Cluster I is solely based on molecular biology techniques.
      Rice Cluster I seems to be widely distributed, particularly in rice fields,
      possibly occupying different niches among the methane producers. One niche seems
      to be methane production on roots driven by plant photosynthesis, contributing
      substantially to the release of methane from rice fields into the atmosphere.

PMID- 16621513
TI  - Transcriptional regulation of the rainbow trout CYP19a gene by FTZ-F1 homologue.
AB  - In rainbow trout, there are at least two CYP19 genes (CYP19a and CYP19b). They
      encode distinct P450arom isozymes that are differentially expressed in the ovary
      and brain. To understand the transcriptional regulation of the rainbow trout
      CYP19a (rtCYP19a) gene in the ovary, we isolated its 5'-flanking region. The
      presence of potential FTZ-F1-binding sites prompted us to isolate the cDNA
      encoding a rainbow trout FTZ-F1 homologue (rtFTZ-F1) and analyze its effect on
      the rtCYP19a gene transcriptional activity. RT-PCR analysis showed overlapping
      expression of the rtCYP19a and rtFTZ-F1 genes in the ovary. Transient
      transfection studies in Chinese hamster ovary-derived CHO-K1 cells revealed that
      the region from -247 to -105, which contains three potential FTZ-F1-binding
      sites, was required for rtFTZ-F1-mediated transcriptional activation of the
      rtCYP19a gene. Among the three potential binding sites, the two from -150 to -142
      and from -118 to -110 showed strong affinities for rtFTZ-F1 in gel shift assays,
      and base substitutions in either site almost abolished the transcriptional
      activation by rtFTZ-F1. Taken together, these results demonstrate that rtFTZ-F1
      plays an important role in the transcriptional regulation of the rtCYP19a gene in
      the ovary.

PMID- 16621515
TI  - Sex steroids and leptin regulate 11beta-hydroxysteroid dehydrogenase I and P450
      aromatase expressions in human preadipocytes: Sex specificities.
AB  - Adipose tissue is an important site of steroid hormone biosynthesis, as type I
      11beta-hydroxysteroid dehydrogenase (HSD1), the enzyme responsible for the
      conversion of cortisone into cortisol and the P450 aromatase, the enzyme
      catalysing androgens aromatization into estrogens, are both expressed in human
      adipose tissue. In the present report, we have investigated the possibility that
      sex steroids and leptin could regulate these two enzymes in cultured
      preadipocytes from men and women intra-abdominal fat depots. In women
      preadipocytes, human recombinant leptin down-regulates HSD1 mRNA expression (
      58%) and P450 aromatase activity (-26%). Conversely, leptin up-regulates the HSD1
      (2.4-fold) and the P450 aromatase (1.6-fold) mRNA expression in men
      preadipocytes. In women preadipocytes, 17beta-estradiol strongly stimulates HSD1
      mRNA expression (10-fold) and, in contrast, decreases by half the P450 aromatase
      expression. In men, 17beta-estradiol has no influence on HSD1 expression but up
      regulates P450 aromatase mRNA expression (2.4-fold). Finally, androgens increase
      by a factor of 2.5-5 the mRNA expression of both enzymes in men. These findings
      suggest that sex steroids and leptin either increase or decrease local cortisol
      and estrogens productions in men or in women preadipocytes, respectively. They
      also indicate that steroid metabolism in adipose tissue is controlled by a
      coordinated regulation of P450 aromatase and HSD1 expressions. Finally, the
      important sex-specific differences described herein may also contribute to
      explain the sexual dimorphism of body fat distribution in humans.

PMID- 16621514
TI  - Responsiveness to estradiol-17beta and to phytoestrogens in primary human
      osteoblasts is modulated differentially by high glucose concentration.
AB  - We have reported previously, that female-derived bone cells responded to 17beta
      estradiol (E(2)) and to raloxifene (Ral), whereas male-derived cells responded
      only to dihydrotestosterone (DHT) when the stimulation of creatine kinase
      specific activity (CK), which is a marker for hormone responsiveness, was
      measured. In cells derived from pre-menopausal women, E(2), G, D and Ral
      stimulated CK to higher extent compared to post-menopausal bone cells, whereas
      quecertin (Qu), carboxy-biochainin A (cBA) and carboxy-genistein (cG) stimulated
      CK in both age groups similarly, and biochainin A (BA) stimulated post-menopausal
      cells to a bit higher extent than pre-menopausal cells. Since the skeletal
      protective effects of estrogens are not discernable in diabetic women, we tested
      in this study, the effects of high glucose concentration in the growth medium, on
      the effects of estrogenic compounds on CK in human-derived bone cells (hObs).
      Female-derived hObs were grown either in normal (4.5 g/l; 22 mM, NG) or high
      glucose (9.0 g/l; 44 mM, HG) for 7 days. HG increased constitutive CK, but
      attenuated E(2)- and DHT-induced CK in female or male hObs, respectively. HG also
      inhibited genistein (G) and daidzein (D) stimulated CK in female hObs, but not
      the effects of biochainin A (BA), quecertin (Qu) or Ral. Intracellular, mainly
      nuclear binding of (3)[H]E(2) was characteristic of the different phytoestrogens
      in female hObs, was abolished by HG. Membranal binding of Eu-Ov-E(2), was
      displaced only by E(2)-Ov, ICI, cG-Ov or cD-Ov but decreased total binding of Eu
      Ov-E(2) in both age groups and completely abolished the competition with E(2)-Ov
      or ICI in both age groups, but the competition with cD-Ov and cG-Ov was decreased
      only slightly but not statistically significant. HG also abolished Eu-BSA-T,
      which bound similarly male-derived hObs. All hObs expressed mRNA for ERalpha and
      ERbeta with higher abundance of ERalpha. HG increased mRNA for both ERs in female
      derived hObs, but decreased mRNA for both ERs in male-derived hObs. Hence, human
      bone cells, which express specific nuclear and membranal binding sites for
      estrogenic compounds, are modulated by HG, leading to altered hormonal
      responsiveness, which might block important effects of estrogenic compounds,
      contributing probably to their decreased skeletal preserving properties under
      hyperglycemia.

PMID- 16621516
TI  - Beta-sitosterol-3-O-beta-D-glucopyranoside: a eukaryotic DNA polymerase lambda
      inhibitor.
AB  - Beta-sitosterol-3-O-beta-D-glucopyranoside (compound 1), a steroidal glycoside
      isolated from onion (Allium cepa L.) selectively inhibited the activity of
      mammalian DNA polymerase lambda (pol lambda) in vitro. The compound did not
      influence the activities of replicative DNA polymerases such as alpha, delta and
      epsilon, but also showed no effect even on the activity of pol beta which is
      thought to have a very similar three-dimensional structure to the pol beta-like
      region of pol lambda. Since parts of compound 1 such as beta-sitosterol (compound
      2) and D-glucose (compound 3) did not influence the activities of any enzymes
      tested, the converted structure of compounds 2 and 3 might be important for pol
      lambda inhibition. The inhibitory effect of compound 1 on both intact pol lambda
      (i.e. residues 1-575) and a truncated pol lambda lacking the N-terminal BRCA1 C
      terminus (BRCT) domain (133-575, del-1 pol lambda) was dose-dependent, and 50%
      inhibition was observed at a concentration of 9.1 and 5.4 microM, respectively.
      The compound 1-induced inhibition of del-1 pol lambda activity was non
      competitive with respect to both the DNA template-primer and the dNTP substrate.
      On the basis of these results, the pol lambda inhibitory mechanism of compound 1
      is discussed.

PMID- 16621518
TI  - The effect of organotin compounds on gender specific androstenedione metabolism
      in the freshwater ramshorn snail Marisa cornuarietis.
AB  - In a recent study, we demonstrated that androstenedione was mainly converted to
      testosterone (T) and 5alpha-dihydrotestosterone (DHT) by digestive gland/gonad
      complex microsomal fractions isolated from male Marisa cornuarietis, whereas it
      was primarily metabolized to 5alpha-dihydroandrostenedione (DHA) by females. In
      the present work, the sexual dimorphic metabolism of androstenedione was further
      investigated, and attributed to a higher 17beta-hydroxysteroid dehydrogenase
      activity in males than in females. Thereafter, the hypothesis was tested that the
      metabolism of androstenedione might be affected by exposure to tributyltin (TBT)
      and triphenyltin (TPT), which are known to induce the development of imposex in
      several gastropod species. The in vitro metabolism of androstenedione,
      particularly the formation of DHA and DHT, was inhibited by both compounds.
      However, in vivo experiments showed no significant alteration in the metabolism
      of androstenedione in males, but a marginal (TBT) and a significant (TPT)
      inhibition of the formation of DHA in females exposed for 150 days to
      concentrations that had significantly induced the development of imposex. The
      ratio DHT+T/DHA, a possible indicator of metabolic androgenization, tended to
      increase (0.43 versus 0.35, p=0.06) in TPT exposed females. However, this ratio
      never reached values comparable to those found in males (11+/-1).

PMID- 16621517
TI  - Nandrolone decanoate impairs exercise-induced cardioprotection: role of
      antioxidant enzymes.
AB  - The beneficial effects of exercise in reducing the incidence of cardiovascular
      diseases are well known and the abuse of anabolic androgenic steroids (AAS) has
      been associated to cardiovascular disorders. Previous studies showed that heart
      protection to ischemic events would be mediated by increasing the antioxidant
      enzyme activities. Here, we investigated the impact of exercise and high doses of
      the AAS nandrolone decanoate (DECA), 10 mgkg(-1) body weight during 8 weeks, in
      cardiac tolerance to ischemic events as well as on the activity of antioxidant
      enzymes in rats. After a global ischemic event, hearts of control trained (CT)
      group recovered about 70% of left ventricular developed pressure, whereas DECA
      trained (DT), control sedentary (CS) and DECA sedentary (DS) animals recovered
      only about 20%. Similarly, heart infarct size was significantly lower in the CT
      group compared to animals of the three other groups. The activities of the
      antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and
      glutathione reductase (GR) were significantly higher in CT animals than in the
      other three groups, whereas catalase activity was not affected in any group.
      Together, these results indicate that chronic treatment with DECA cause an
      impairment of exercise induction of antioxidant enzyme activities, leading to a
      reduced cardioprotection upon ischemic events.

PMID- 16621519
TI  - Differential effect of DHEA on mitogen-induced proliferation of T and B
      lymphocytes.
AB  - Dehydroepiandrosterone (DHEA) is the predominant steroid hormone secreted by
      adrenal gland, and it has been proposed in recent years that DHEA has significant
      effects on immune function. We investigated the effect of DHEA (1 x 10(-5) - 1 x
      10(-8)M) on proliferation of human T cells and B cells and on immunoglobulin
      production, a representative function of B cells. High doses of DHEA (1 x 10(-5))
      significantly inhibited proliferation of peripheral blood mononuclear cells
      (PBMCs) and T cells induced by T cell mitogens hemagglutinin (PHA) and
      concanavalin A (Con A). Proliferation of PBMCs induced by B cell mitogens
      pokeweed mitogen (PWM) was increased by 1 x 10(-7) - 1 x 10(-6)M DHEA.
      Proliferation of PBMCs and B cells induced by Staphylococcus aureus Cowan strain
      I (SAC) was not significantly changed at any concentrations of DHEA. However, a
      concentration of 1 x 10(-7)M DHEA tended to potentiate their proliferation. This
      study suggested that DHEA acted on T and B lymphocytes differentially in immune
      system.

PMID- 16621520
TI  - Quantitation and cellular localization of 11beta-HSD1 expression in murine
      thymus.
AB  - 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1), an NADPH-dependent
      reductase, functions in intact cells to convert inactive 11-keto metabolites of
      glucocorticoids into biologically active glucocorticoids. The enzyme is thus
      capable of amplifying glucocorticoid action in tissues in which it is expressed.
      In the experiments presented here, we show that 11beta-HSD1 is expressed in the
      murine thymus and that expression increases from late fetal development to
      maximal levels in the adult thymus. Quantitative real time-PCR, immunoblots, and
      assays of enzymatic activity reveal adult thymic expression of 11beta-HSD1 mRNA
      and protein at levels approximately 6-7% of those observed in liver.
      Immunofluorescence experiments show that the enzyme is expressed in the medullary
      thymocytes and thymocytes present at the corticomedullary junction. These
      experiments extend our recognition of 11beta-HSD1 expression in cells of the
      immune system and lend support to the notion that glucocorticoid signaling and
      amplification of those signals by regeneration of active glucocorticoids from
      inactive 11-keto metabolites might impact intrathymic T cell development and the
      establishment of the immune repertoire.

PMID- 16621521
TI  - Estradiol inhibits adhesion and promotes apoptosis in murine osteoclasts in
      vitro.
AB  - Osteoporosis caused by estrogen deficiency is characterized by enhanced bone
      resorption mediated by osteoclasts. Adhesion to bone matrix and survival of
      differentiated osteoclasts is necessary to resorb bone. The aim of our study was
      to investigate the in vitro effects of estradiol on murine osteoclasts. RAW 264.7
      cells treated with 30 ng/ml RANK-L were used as a model for osteoclastogenesis.
      Estradiol (10(-8)M) for 5 days induced an inhibition of osteoclast
      differentiation and beta3 expression. Estradiol inhibited significantly the
      adhesion of mature osteoclasts by 30%. Furthermore estradiol-induced apoptosis
      shown by with nuclear condensation and Bax/Bcl2 ratio. In addition, estradiol
      enhanced caspase-3, -8 and -9 activities. This effect completely disappeared
      using specific caspase-8 inhibitor. However, increased caspase-3 activity by
      estradiol was observed in the presence of caspase-9 inhibitor, indicating the
      preferential involvement of caspase-8 pathway. Fas and FasL mRNA expression was
      not regulated by estradiol. However, estradiol enhanced caspase-3 activity in Fas
      induced apoptosis on mature osteoclasts, suggesting that this might interact with
      the Fas-signaling pathway. These data suggest that estradiol decreases bone
      resorption by several mechanisms including adhesion and apoptosis of osteoclasts.

PMID- 16621522
TI  - Androgen glucuronides, instead of testosterone, as the new markers of androgenic
      activity in women.
AB  - Despite the long series of cohort studies performed during the last 20 years, the
      correlation between serum testosterone and any clinical situation believed to be
      under androgen control in women has remained elusive. This is likely related to
      the recent finding that the androgens made locally in large amounts in peripheral
      tissues from the precursor dehydroepiandrosterone (DHEA) act in the same cells
      where synthesis takes place and are not released in significant amounts in the
      circulation, thus making unreliable the measurement of serum testosterone as
      marker of total androgenic activity. The objective is to determine if serum
      androgen glucuronides can be replaced by testosterone or another steroid as
      measure of androgenic activity. Since the glucuronide derivatives of androgens
      are the obligatory route of elimination of all androgens, these metabolites were
      measured by liquid chromatography tandem mass spectrometry under basal conditions
      in 377 healthy postmenopausal women aged 55-65 years as well as in 47
      premenopausal women aged 30-35 years while testosterone was assayed by gas
      chromatography mass spectrometry. No correlation was found between the serum
      concentration of testosterone and that of androsterone glucuronide (ADT-G) or
      androstenediol glucuronide (3alpha-diol-G), the androgen metabolites which
      account for the total pool of androgens. The present data show that measurement
      of the total pool of androgens reflected by the serum levels of ADT-G and 3alpha
      diol-G cannot be replaced by serum testosterone or any other steroid, including
      DHEA or DHEA sulphate. These findings may have implications for women with
      androgen deficiency involving osteoporosis, obesity, type 2 diabetes, sexual
      dysfunction, loss of muscular strength and a series of other clinical situations
      affecting women's health. Measuring ADT-G and 3alpha-diol-G might identify cases
      of true androgen deficiency and provide an opportunity to offer appropriate
      androgen therapy.

PMID- 16621523
TI  - Systemic distribution and tissue localizations of human 17beta-hydroxysteroid
      dehydrogenase type 12.
AB  - The 17beta-hydroxysteroid dehydrogenases (HSDs) are enzymes that catalyze the
      reduction of 17-ketosteroids or the oxidation of 17beta-hydroxysteroids. 17beta
      HSD type 12, the most recently cloned member of this gene family, was classified
      into the 17beta-HSD family based on sequence homology, rather than steroid
      catalyzing activity. Meanwhile, it has been reported that 17beta-HSD type 12 may
      be involved in fatty acid synthesis. To better understand the role of 17beta-HSD
      type 12 in lipid metabolism, we determined the detailed systemic distribution and
      tissue localizations of 17beta-HSD type 12, which, due partly to the lack of
      antibodies, had not yet been studied. We carried out these investigations by
      quantitative reverse transcription (RT)-PCR, Northern blot analysis, and
      immunohistochemistry, using an antibody against 17beta-HSD type 12 that we have
      generated. 17beta-HSD type 12 is highly expressed in organs related to lipid
      metabolism such as liver, kidney, heart and skeletal muscle. 17beta-HSD type 12
      is also detected in endocrine-related organs such as pancreas, pituitary gland,
      adrenal gland, testis and placenta, and in the gastrointestinal tract, which
      point to the possible involvement of 17beta-HSD type 12 in the regulation of
      lipid biosynthesis and steroid metabolism. These results support previous reports
      and solidify the possibility that 17beta-HSD type 12 may play critical roles in
      the physiological processes, such as fatty acid synthesis, in addition to the
      steroid metabolism.

PMID- 16621524
TI  - Reconstitution of the type II [3H]estradiol binding site with recombinant histone
      H4.
AB  - Previously, we identified the rat uterine nuclear type II [3H]estradiol binding
      site as histone H4 and an unknown 35 kDa protein with histone H4
      immunoreactivity. Studies using calf thymus histones indicated that the 35 kDa
      protein was likely a dimer of histone H3 and H4. Further study of the type II
      site required methodology for producing sufficient quantities of recombinant
      histones, which retained ligand-binding properties. A variety of production
      methods produce sufficient quantities of histone for binding analyses were
      evaluated prior to finding a successful technique. The present studies describe
      techniques for the production of recombinant histones that retain the ligand
      binding properties of type II binding site. Binding studies with recombinant
      protein mirrored [3H]estradiol binding assays with rat uterine nuclear
      preparations. Histone H4 specifically binds [3H]estradiol with a low affinity (Kd
      approximately 20 nM) and in a cooperative fashion (curvilinear Scatchard plot;
      Hill coefficient approximately 4). Although histone H3 does not appear to bind
      ligand, regeneration of the histone H3/H4 pair produced a 35 kDa protein
      equivalent to the 35 kDa protein labeled with [3H]luteolin in rat uterine nuclear
      extracts and calf thymus histones. These data confirm the identification of
      histone H4 as a key component of the type II site. Future studies with
      recombinant proteins will lead to the identification of the "nucleosomal ligand
      binding domain" for methyl-p-hydroxyphenyllactate (MeHPLA) and related ligands
      and delineation of their epigenetic control of gene expression and cell
      proliferation.

PMID- 16621525
TI  - Dehydroepiandrosterone sulphate sulphohydrolase [correction of sulphoydrolase]
      from human placenta microsomes--properties of the purified enzyme.
AB  - A form of steroid sulphate sulphohydrolase (EC 3.1.6.2) hydrolysing the
      dehydroepiandrosterone sulphate (DHEAS-ase) was purified from human placenta
      microsomes. During the purification procedure the DHEAS-ase was separated from
      the oestrone sulphate sulphohydrolase (OS-ase). The purified DHEAS-ase revealed
      specific activity of 1520 nmolxmin-1xmgprotein-1 and exhibited optimal activity
      at pH 8.4. The Km value was established to be 3.3+/-0.07x10(-5) M. The pI value
      was around 8.7. The molecular weight estimated by gel filtration was 7.4 kDa. The
      purified DHEAS-ase was not sensitive to the common sulphohydrolase inhibitors,
      such as phosphate, sulphate and sulphide ions, but was inhibited by several
      phosphohydrolase inhibitors (ammonium molybdate, vanadium oxide(V), zinc
      acetate). Steroids effected inhibition or activation of the purified enzyme. The
      data concerning substances reacting with -SH groups suggest that in the
      physiological conditions DHEAS-ase is controlled by the redox status of the cell.

PMID- 16621526
TI  - Are estrogen receptor content in breast cancer and effects of tamoxifen on sex
      hormone-binding globulin markers for individual estrogen sensitivity?
AB  - Individual women differ with respect to their sensitivity to estrogen and serum
      levels of sex hormone-binding globulin (SHBG) may reflect the individual
      response. We found a significant correlation between estrogen receptor (ER)
      concentrations in breast cancer tissue and SHBG levels during tamoxifen
      treatment. Estrogen sensitivity may be a general characteristic common to various
      organs and different between individual women.

PMID- 16621527
TI  - A review on hydrolytic enzymes in the treatment of wastewater with high oil and
      grease content.
AB  - Wastewater from dairies and slaughterhouses contains high levels of fats and
      proteins that present low biodegradability. A large number of pretreatment
      systems are employed to remove oil and grease (O&G) to prevent a host of problems
      that may otherwise arise in the biological process, and reduce the efficiency of
      the treatment station. Problems caused by excessive O&G include a reduction in
      the cell-aqueous phase transfer rates, a sedimentation hindrance due to the
      development of filamentous microorganisms, development and flotation of sludge
      with poor activity, clogging and the emergence of unpleasant odors. Therefore the
      application of a pretreatment to hydrolyze and dissolve lipids may improve the
      biological degradation of fatty wastewaters, accelerating the process and
      improving time efficiency. However thus far, only a few studies describing the
      degradation of fats and oils by alkaline/acid/enzymatic hydrolysis have been
      reported; the treatment of effluents from several origins is a new and promising
      application for lipases. Among the strains that produce the hydrolytic enzymes
      studied, the fungus Penicillium restrictum is a particularly promising one. When
      cultivated in low-cost solid medium composed of agro-industrial waste, P.
      restrictum produces a pool of hydrolases capable of degrading the most complex
      organic compounds. This degradation enables a considerable increase in organic
      matter removal efficiency to be realized, which results in the attainment of a
      high-quality effluent in the subsequent biological treatment stage. Consequently,
      there is presently a wide variety of ongoing scientific investigation in the
      field of developing enzymatic hydrolysis processes to precede traditional
      biological treatment.

PMID- 16621528
TI  - Carboxylate bioisosteres of pregabalin.
AB  - Several beta-amino tetrazole analogs of gabapentin 1 and pregabalin 2 were
      prepared by one of two convergent, highly efficient routes, and their affinity
      for the alpha(2)-delta protein examined. Two select compounds with potent
      affinity for alpha(2)-delta, 8a and 16a, were subsequently tested in vivo in an
      audiogenic seizure model and found to elicit protective effects.

PMID- 16621529
TI  - A new drug-release method using the Staudinger ligation.
AB  - Many drugs induce severe side-effects caused by their lack of selectivity. One
      way to overcome this problem is to design a specific system which releases a free
      drug in a controlled manner. Herein we describe a new way to liberate a drug from
      a prodrug using the Staudinger ligation as the trigger.

PMID- 16621530
TI  - Identification of novel PPARalpha ligands by the structural modification of a
      PPARgamma ligand.
AB  - To develop novel PPARalpha ligands, we designed and synthesized several 3-{3-[2
      (nonylpyridin-2-ylamino)ethoxy]phenyl}propanoic acid derivatives. Compound 10,
      the meta isomer of a PPARgamma agonist 1, has been identified as a PPARalpha
      ligand. The introduction of methyl and ethyl groups at the C-2 position of the
      propanoic acid of 10 further improved the PPARalpha-binding potency.

PMID- 16621531
TI  - Design and synthesis of a biotin-tagged photoaffinity probe of paeoniflorin.
AB  - A trifunctional probe (binding element-photoreactive group-affinity tag) of
      natural product paeoniflorin was designed and synthesized based on the previous
      primary structure-activity relationship. This new probe is a potential tool for
      labeling, purification, and identification of the target proteins.

PMID- 16621532
TI  - Development of new brain imaging agents based upon nocaine-modafinil hybrid
      monoamine transporter inhibitors.
AB  - 11C-labeled (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1-methylpiperidin-3
      yl]methylsulfanyl]ethanol ([11C]5) and (+)-trans-2-[[(3R,4S)-4-(4-chlorophenyl)-1
      methylpiperidin-3-yl]methylsulfanyl]-1-(piperidin-1-yl)ethanone ([11C]6) were
      synthesized and evaluated as new imaging agents for the norepinephrine
      transporter (NET). [11C]5 and [11C]6 display high affinity for the NET in vitro
      (Ki = 0.94 and 0.68 nM, respectively) and significant selectivity over the
      dopamine (DAT) and serotonin transporters (SERT). Because of their high affinity
      and favorable transporter selectivities we speculated that these ligands might
      serve as useful PET agents for imaging NET in vivo. Contrary to our expectations,
      both of these ligands provided brain images that were more typical of those shown
      by agents binding to the DAT.

PMID- 16621533
TI  - Inhibitory activity of cyclohexenyl chalcone derivatives and flavonoids of
      fingerroot, Boesenbergia rotunda (L.), towards dengue-2 virus NS3 protease.
AB  - Boesenbergia rotunda (L.) cyclohexenyl chalcone derivatives, 4-hydroxypanduratin
      A and panduratin A, showed good competitive inhibitory activities towards dengue
      2 virus NS3 protease with the Ki values of 21 and 25 microM, respectively, whilst
      those of pinostrobin and cardamonin were observed to be non-competitive. NMR and
      GCMS spectroscopic data formed the basis of assignment of structures of the six
      compounds isolated.

PMID- 16621535
TI  - Fully flexible docking models of the complex between alpha7 nicotinic receptor
      and a potent heptapeptide inhibitor of the beta-amyloid peptide binding.
AB  - The heptapeptide IQTTWSR (IQ), recently reported as inhibitor of the beta-amyloid
      (Abeta) binding to nicotinic acetylcholine receptors (nAChrs), was docked to the
      homology model of the alpha7 nicotinic acetylcholine receptor. The most
      representative models were further subjected to molecular dynamics simulations.
      The data obtained here suggest that Abeta needs highly specific structural motifs
      to bind to the alpha7nAChR. These structural motifs are located principally in
      the upper and lower surroundings of loop C, including loop F and sheets beta1,
      beta2, beta6, beta9, and beta10 of the receptor. Overall, these results suggest
      that IQ can be mimicked by more bioavailable, stable compounds that would be
      helpful for the understanding of the Abeta binding site and its dynamics, and for
      the design of novel agents to be used as an effective alternative against
      Alzheimer's disease.

PMID- 16621534
TI  - Synthesis of pyrazoles and isoxazoles as potent alpha(v)beta3 receptor
      antagonists.
AB  - We describe a series of pyrazole and isoxazole analogs as antagonists of the
      alpha(v)beta3 receptor. Compounds showed low to sub-nanomolar potency against
      alpha(v)beta3, as well as good selectivity against alpha(IIb)beta3. In HT29
      cells, most analogs also demonstrated significant selectivity against
      alpha(v)beta6. Several compounds showed good pharmacokinetic properties in rats,
      in addition to anti-angiogenic activity in a mouse corneal micropocket model.
      Compounds were synthesized in a straightforward manner from readily available
      glutarate precursors.

PMID- 16621536
TI  - Spectroscopic studies of the interaction between quercetin and G-quadruplex DNA.
AB  - Quercetin is a kind of flavonoid which has been proved to exhibit anti-tumor
      activity. The interaction modes of quercetins with monomeric and dimeric G
      quadruplexes were studied by absorption, fluorescence, CD, and (1)H NMR
      spectroscopies. The ligands were found to be stacked with terminal tetrads of
      monomeric G-quadruplexes by intercalation and bound to dimeric G-quadruplexes by
      groove binding.

PMID- 16621537
TI  - Carbonic anhydrase inhibitors: inhibition of the cytosolic human isozyme VII with
      anions.
AB  - An inhibition study of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isozyme
      VII (hCA VII) with anions has been conducted. Cyanate, cyanide, and
      hydrogensulfite were weak hCA VII inhibitors (K(I)s in the range of 7.3-15.2 mM).
      Cl- and HCO3- showed good inhibitory activity against hCA VII (K(I)s of 0.16-1.84
      mM), suggesting that this enzyme is not involved in metabolons with anion
      exchangers or sodium bicarbonate cotransporters. The best inhibitors were
      sulfamate, sulfamide, phenylboronic, and phenylarsonic acid (K(I)s of 6.8-12.5
      microM).

PMID- 16621538
TI  - Evaluation of the eutomer of 4-{3-(4-chlorophenyl)-3-hydroxypyrrolidin-1-yl}-1-(4
      fluorophenyl)butan-1-one, {(+)-SYA 09}, a pyrrolidine analog of haloperidol.
AB  - Enantiomeric separation of the racemic 4-{3-(4-chlorophenyl)-3-hydroxypyrrolidin
      1-yl}-1-(4-fluorophenyl)butan-1-one, a pyrrolidine analog of haloperidol, {(+/-)
      SYA 09}, and subsequent binding studies revealed that most of the binding
      affinity at dopamine and serotonin receptors resides in the (+)-isomer {(+)-SYA
      09} or the eutomer. Further pharmacological evaluation of the eutomer revealed
      that it has a higher affinity for the dopamine D4 (DAD4) receptor subtype (Ki =
      3.6 nM) than for the DAD2 subtype (Ki = 51.1 nM) with a ratio of 14.2 (D2Ki/D4Ki
      ratio = 14.2). In an animal model of antipsychotic efficacy, the (+)-SYA 09 was
      efficacious with an ED50 value of 1.6 mg/kg, i.p., and at twice this value, (+)
      SYA 09 did not induce significant catalepsy in rats.

PMID- 16621540
TI  - Stereoselective synthesis of dinucleoside boranophosphates by an
      oxazaphospholidine method.
AB  - A stereoselective synthesis of dinucleoside boranophosphates by using nucleoside
      3'-oxazaphospholidine derivatives is described. The diastereoselectivity of the
      internucleotidic bond formation reactions varied with the nucleobase used. (Rp)-
      and (Sp)-dithymidine boranophosphates were synthesized with excellent
      diastereoselectivity both in solution and on a solid-support, whereas a loss of
      diastereopurity was observed for the 2'-deoxycytidine derivative having an
      unprotected nucleobase amino group. On the other hand, complete chemoselectivity
      of the 3'-oxazaphospholidine derivatives toward hydroxy groups over amino groups
      was serendipitously found during the study. This unique chemoselectivity of the
      3'-oxazaphospholidine derivatives was investigated by comparing them with the
      conventional nucleoside 3'-phosphoramidite.

PMID- 16621539
TI  - Function of the alkyl side chains of Deltalac-acetogenins in the inhibitory
      effect on mitochondrial complex I (NADH-ubiquinone oxidoreductase).
AB  - We synthesized a series of Deltalac-acetogenins in which the two alkyl side
      chains were systematically modified, and examined their inhibitory effect on
      bovine heart mitochondrial complex I (NADH-ubiquinone oxidoreductase). The
      results revealed that the physicochemical properties of the side chains, such as
      the balance of hydrophobicity and the width (or bulkiness) of the chains, are
      important structural factors for a potent inhibitory effect of amphiphilic
      Deltalac-acetogenins. This is probably because such properties decide the precise
      location of the hydrophilic bis-THF ring moiety in the enzyme embedded in the
      inner mitochondrial membrane.

PMID- 16621541
TI  - 2,3,7-Trisubstituted pyrazolo[1,5-d][1,2,4]triazines: functionally selective
      GABAA alpha3-subtype agonists.
AB  - Novel synthetic routes have been devised for the preparation of previously
      inaccessible 2,3,7-trisubstituted pyrazolo[1,5-d][1,2,4]triazines 2. These
      compounds are high affinity ligands for the GABA(A) benzodiazepine binding site
      and some analogues show functional selectivity for agonism at alpha3-containing
      receptors over alpha1-containing receptors with the lead compound being 32.

PMID- 16621542
TI  - Design and semisynthesis of novel fredericamycin A derivatives with an improved
      antitumor profile.
AB  - We report the design, semisynthesis, and biological activity of a series of
      fredericamycin (1) derivatives. Within this series compound 1e combines low
      nanomolar cytotoxic potency in vitro, increased tumor cell line selectivity, and
      in vivo activity in a human xenograft model.

PMID- 16621543
TI  - 2-Aryl(pyrrolidin-4-yl)acetic acids are potent agonists of sphingosine-1
      phosphate (S1P) receptors.
AB  - A series of 2-aryl(pyrrolidin-4-yl)acetic acids were synthesized and their
      biological activities were evaluated as agonists of S1P receptors. These analogs
      were able to induce lowering of lymphocyte counts in the peripheral blood of mice
      and were found to have good overall pharmacokinetic properties in rat.

PMID- 16621544
TI  - 8-(Pyren-1-yl)-2'-deoxyguanosine as an optical probe for DNA hybridization and
      for charge transfer with small peptides.
AB  - 8-(Pyren-1-yl)-2'-deoxyguanosine (Py-G) was incorporated synthetically as an
      optical probe into oligonucleotides. The Py-G group in DNA does not discriminate
      between any of the four natural nucleosides as a counterbase and exhibits altered
      optical properties in single strands versus double strands. Thus, the duplex
      hybridization of Py-G-modified DNA can be observed by both fluorescence and
      absorption spectroscopy. Moreover, Py-G in DNA can be applied as photoinducable
      donor for charge transfer processes with small peptides.

PMID- 16621545
TI  - Synthesis of Hsp90 dimerization modulators.
AB  - The synthesis and evaluation of several chemical modulators of heat shock protein
      90 (Hsp90) dimerization is presented. These agents may represent useful tools to
      study the importance of N-terminal dimerization and also to determine subunit
      interface(s) in Hsp90.

PMID- 16621546
TI  - Design, synthesis, and biological evaluation of indole derivatives as novel
      nociceptin/orphanin FQ (N/OFQ) receptor antagonists.
AB  - A novel series of 2-(1,2,4-oxadiazol-5-yl)-1H-indole derivatives as
      nociceptin/orphanin FQ (N/OFQ) receptor antagonists was discovered. Systematic
      modification of our original lead by changing the pendant functional groups,
      linker, heterocyclic core, and basic side chain revealed the structure-activity
      requirements for this novel template and resulted in the identification of more
      potent analog with improved potency as compared to the parent compound.

PMID- 16621547
TI  - New potential inhibitors of cyclin-dependent kinase 4: design and synthesis of
      pyrido[2,3-d]pyrimidine derivatives under microwave irradiation.
AB  - A simple and efficient synthesis of 2-amino pyrido[2,3-d]pyrimidine derivatives
      was accomplished via a three-component reaction under microwave irradiation
      without catalyst. This method had many dramatic advantages such as the short
      reaction time, high yield, and broad substrate scope, as well as convenient
      operation. We provide new series of potential biologically active compounds as
      inhibitors of Cdk4.

PMID- 16621548
TI  - Synthesis and photocytotoxic activity of new chlorin-polyamine conjugates.
AB  - This paper reports the synthesis of new chlorin-polyamine conjugates designed to
      improve the targeting of cancer cells. Photocytotoxic activity of these
      photosensitizers was tested against human chronic myelogenous leukemia cells
      (K562) and compared to the effects of Photofrin II and chlorin e6.

PMID- 16621549
TI  - Novel 5-azaindole factor VIIa inhibitors.
AB  - The discovery and development of 5-azaindole factor VIIa inhibitors will be
      described.

PMID- 16621550
TI  - Phosphonic acid-containing analogues of mycophenolic acid as inhibitors of IMPDH.
AB  - The design, synthesis, and IMPDH inhibitory activity of a series of phosphonic
      acid-containing analogues of mycophenolic acid are described.

PMID- 16621551
TI  - Synthesis and antibacterial activity of nocathiacin I analogues.
AB  - Stereoselective reduction of dehydroalanine double bond in nocathiacin I afforded
      the primary amide 2. Enzymatic hydrolysis of the amide 2 provided the carboxylic
      acid 3, which upon coupling with a variety of amines furnished amides 4-32. Some
      of these semi-synthetic derivatives have retained very good antibacterial
      activity and have improved aqueous solubility.

PMID- 16621552
TI  - Fluorophor-labeled spermidine derivatives as fluorescent markers in optical tumor
      imaging.
AB  - Up-regulation of polyamine transporters on the surface of tumor cells and the
      internalization of biogenic polyamines by active transport processes may be
      exploited for the accumulation of spermidine derivatives as reporter molecules.
      We have synthesized and tested fluorophor-labeled spermidine derivatives for the
      development of a new class of intraoperative tumor imaging agents. In vitro
      uptake experiments and initial in vivo imaging studies illustrated that
      fluorophor tagged spermidine derivatives show tumor accumulation.

PMID- 16621553
TI  - Synthesis and biological investigation of S-aryl-S-DABO derivatives as HIV-1
      inhibitors.
AB  - S-Aryl-S-DABO derivatives, a novel subclass of S-DABO anti-HIV-1 agents, were
      synthesized via Ullmann type reaction starting from the corresponding 2
      thiouracils by the aid of microwave irradiation. The results of their evaluation
      as inhibitors of RT are reported together with their antiviral activity in
      cellular assays.

PMID- 16621554
TI  - DNA and LNA oligonucleotides containing N2'-functionalised derivatives of 2'
      amino-2'-deoxyuridine.
AB  - Synthesis of various N-acylated derivatives of 2'-amino-2'-deoxyuridine is
      described together with their incorporation into DNA and LNA oligonucleotides
      using the phosphoramidite approach on an automated DNA synthesizer. The thermal
      stabilities of duplexes formed by these 2'-amino-DNA-modified DNA or LNA/DNA
      chimeric strands and complementary DNA or RNA strands have been studied.
      Introduction of LNA monomers around the functionalised 2'-amino-DNA modifications
      results in reversal of the affinity-decreasing effect of the latter. This
      represents a novel general approach for design and synthesis of high-affinity
      functionalised oligonucleotides for biotechnological or medicinal applications.

PMID- 16621555
TI  - The ortho hydroxy-amino group: another choice for synthesizing novel
      antioxidants.
AB  - Four ortho hydroxy-amino derivatives have been designed based on the structures
      of flavonoids to explore the effect of the ortho hydroxy-amino group on the
      antioxidant properties of molecules, and their bond dissociation enthalpies
      (BDE), ionization potentials (IP), the highest occupied molecular orbitals
      (HOMO), and spin densities have been calculated. The results reveal that the
      ortho hydroxy-amino group plays an important role in promoting the antioxidant
      properties of molecules because of its lowering effect on BDE, IP, and spin
      density. The derivatives with ortho hydroxy-amino group show stronger antioxidant
      activity than the derivatives with mono hydroxy or ortho dihydroxy group. Thus,
      the ortho hydroxy-amino group can be used as another potential functional group
      to synthesize novel antioxidants as guessed.

PMID- 16621556
TI  - Synthetic studies of neoclerodane diterpenes from Salvia divinorum: selective
      modification of the furan ring.
AB  - A synthetic sequence has been developed to selectively functionalize the furan
      ring of the natural product salvinorin A (2a). The synthetic routes described
      convert the furan ring in 2a into an N-sulfonylpyrrole, oxazole or an oxadiazole.
      In addition, a procedure has been found to remove the furan skeleton completely.
      Biological results indicate that replacement of the furan ring with an N
      sulfonylpyrrole leads to reduced affinity and efficacy at kappa opioid receptors.

PMID- 16621557
TI  - Differential calcineurin signalling activity and regeneration efficacy in
      diaphragm and limb muscles of dystrophic mdx mice.
AB  - Calcineurin activity is essential for successful skeletal muscle regeneration in
      young mdx mice and in wild type mice following myotoxic injury and cryodamage. In
      mature myofibres of adult mdx mice, calcineurin stimulation can ameliorate the
      dystrophic pathology. The aim of this study was to test the hypothesis that the
      more severe dystrophic pathology of the diaphragm compared with hindlimb muscles
      of mdx mice could be attributed to aberrant calcineurin signalling and that due
      to ongoing regeneration calcineurin activity would be greater in muscles of adult
      mdx than wild type mice. Differences in markers of regeneration between tibialis
      anterior and diaphragm muscles were also characterised, to determine whether
      there was an association between regeneration efficacy and calcineurin activity
      in dystrophic muscles. In diaphragm muscles of adult mdx mice, the proportion of
      centrally nucleated fibres and developmental myosin heavy chain protein
      expression was lower and myogenin protein expression was higher than in tibialis
      anterior muscles. Calcineurin and activated NFATc1 protein content and
      calcineurin phosphatase activity were higher in muscles from mdx than wild type
      mice and calcineurin activation was greater in diaphragm than tibialis anterior
      muscles of mdx mice. Thus, despite greater calcineurin activity in diaphragm
      compared to hindlimb muscles, regeneration events downstream of myoblast
      differentiation and mediated by the injured myofibre were severely compromised.

PMID- 16621558
TI  - Long-term improvement of slow-channel congenital myasthenic syndrome with
      fluoxetine.
AB  - We report on a 15-year-old patient who was diagnosed with congenital myasthenic
      syndrome (CMS) at the age of 7 months. At initial diagnosis, the CMS was not
      further characterized. The patient was treated for several years with the
      anticholinesterase drug (Mestinon), without clinical benefit. The patient
      deteriorated progressively and became dependent on home nocturnal ventilatory
      support, being unable to take part in daily life activities at age of 12 years.
      At age 14, the slow-channel syndrome mutation CHRNE L269F (805C>T) was detected
      and acetylcholinesterase inhibitor therapy was immediately stopped. Fluoxetine
      therapy was started and gradually increased over 2 months. The boy improved
      dramatically in strength and endurance and was taken off ventilatory support 1
      month after the fluoxetine therapy was initiated. The clinical improvement was
      confirmed by functional respiratory and electrophysiological tests.

PMID- 16621559
TI  - Predictors of severe chest infections in pediatric neuromuscular disorders.
AB  - Chest infections are serious complications in neuromuscular disorders. The
      predictive values of lung and respiratory muscle function including peak cough
      flow still remain unclear. We performed retrospective analysis of 46 children and
      adolescents (12.7+/-3.7 years) in whom lung function, respiratory muscle function
      and peak cough flows had been obtained. Data were related to: (1). number of
      chest infections and days of antibiotic treatment the year prior to the study and
      (2). history of severe chest infection requiring hospital admission. The number
      of chest infections and the number of days treated with antibiotics correlated
      with Inspiratory Vital Capacity IVC, peak cough flow PCF and Peak Expiratory
      Pressure PEP. Twenty-two patients were hospitalized at least once due to severe
      chest infection. IVC (0.65 vs. 1.44 l; P<0.0001) and PCF (116 vs. 211 l/min;
      P<0.0005) in these patients were significantly lower than in the non-hospitalized
      group. IVC<1.1l and PCF<160 l/min were specific and sensitive thresholds to
      discriminate between patients who had already suffered severe chest infections
      and those who had not. Therefore, spirometry and peak cough flow are reliable
      tests to identify patients at high risk for severe chest infections. Patients
      with IVC below 1.1l and/or PCF below 160 l/min should be well monitored and
      introduced to assisted coughing techniques.

PMID- 16621560
TI  - Subclavicular recurrence of breast cancer: does surgery play a role?
AB  - Occasionally, breast cancer relapses in the subclavicular region. In patients
      with failed multimodal treatment, or in those who develop an isolated recurrence,
      surgical resection may be useful to remove all macroscopically evident diseases.
      However, the procedure may be technically demanding and there are no published
      data regarding its benefits. The aim of the present study was to evaluate the
      feasibility and safety of subclavicular resection in breast cancer and provide
      indications as to whether it can contribute to disease control. We used a
      transpectoral approach to surgically remove isolated breast cancer recurrence in
      the subclavicular region in seven consecutive patients presenting over 2 years;
      in the eighth case a transmanubrial approach was necessary. We found that the
      surgical approach proposed is feasible and safe, with a 75% rate of complete
      resection; however, the series was characterised by a high rate of local and
      distant relapse. We conclude that the technique may be useful, in selected cases,
      for palliation only.

PMID- 16621561
TI  - Apoptosis-inducing factor: vital and lethal.
AB  - Apoptosis-inducing factor (AIF) is a NADH oxidase with a local redox function
      that is essential for optimal oxidative phosphorylation and for an efficient anti
      oxidant defense. The absence of AIF can cause neurodegeneration, skeleton muscle
      atrophy and dilated cardiomyopathy. In many models of apoptosis, AIF translocates
      to the nucleus, where it induces chromatin condensation and DNA degradation. The
      nuclear localization of AIF can be inhibited by blocking upstream signals of
      apoptosis. The contribution of AIF to cell death depends on the cell type and
      apoptotic insult and is only seen when caspases are inhibited or not activated.
      It is unknown to what extent and through which mechanisms AIF contributes to the
      induction of cell death. Here, we discuss recent progress in the quest to
      understand the contribution of AIF to life and death.

PMID- 16621562
TI  - Repairing subtelomeric DSBs at the nuclear periphery.
AB  - Nuclear organization creates microenvironments favoring distinct nuclear
      functions. In budding yeast, silent chromatin regions such as telomeres are
      clustered at the nuclear periphery, creating zones of transcriptional repression.
      Recently, in the Journal of Cell Biology, Therizols et al. report that "telomere
      tethering at the nuclear periphery is essential for DNA double strand break
      repair in subtelomeric regions". Here, we discuss these results and their
      functional implications.

PMID- 16621563
TI  - A leadership programme for critical care.
AB  - This paper describes the genesis, design and implementation of a leadership
      programme for critical care. This was an initiative funded by the National Health
      Service (NHS) Nursing Leadership Project and had at the core of its design
      flexibility to meet the needs of the individual hospitals, which took part in it.
      Participation was from the multi-disciplinary critical care team. Six NHS
      hospitals took part in the programme which was of 20 days duration and took place
      on hospital sites. The programme used the leadership model of as its template and
      had a number of distinct components; a baseline assessment, personal development,
      principles of leadership and critical case reviews. The programme was underpinned
      by three themes; working effectively in multi-professional teams to provide
      patient focussed care, managing change through effective leadership and
      developing the virtual critical care service. Each group set objectives pertinent
      to their own organisation's needs. The programme was evaluated by a self
      reporting questionnaire; group feedback and feedback from stakeholders. Programme
      evaluation was positive from all the hospitals but it was clear that the impact
      of the programme varied considerably between the groups who took part. It was
      noted that there was some correlation between the success of the programme and
      organisational 'buy in' as well as the organisational culture within which the
      participants operated. A key feature of the programme success was the critical
      case reviews, which were considered to be a powerful learning tool and medium for
      group learning and change management.

PMID- 16621564
TI  - The experiences of trained nurses caring for critically ill patients within a
      general ward setting.
AB  - BACKGROUND: The concept that critical care is a service rather than a location
      has been increasingly highlighted. However, there is limited information
      regarding nurses' perceptions of caring for critically ill patients outside of
      high dependency areas. AIM: The aim of this study was to explore the factors that
      influence the experiences of trained nurses caring for critically ill patients
      within a general ward setting. METHOD: This was an exploratory, descriptive study
      combining an interview and questionnaire methodology. A purposive sample of seven
      trained nurses reflecting a range of grades and experience, from one medical ward
      were selected. A semi-structured interview combined with an attitudinal scale was
      utilised. RESULTS: Following analysis five key themes emerged: clinical
      environment, professional relationships, patient assessment, nurse's feelings and
      educational needs. CONCLUSION: Whilst the findings of this study cannot be
      generalised, analysis of the data has provided an insight into the complex
      factors that effect care delivery. In order to respond to this study's findings,
      there are resource implications. Educational requirements and communication
      skills will need to be developed.

PMID- 16621566
TI  - Modification of human postural responses to soleus muscle vibration by rotation
      of visual scene.
AB  - Sensory interaction in posture control in 20 healthy subjects was investigated by
      postural responses to differently timed proprioceptive and visual stimulation. As
      proprioceptive stimulation was used both soleus muscles vibration. Visual
      stimulation was rotating disc moving in forward and backward direction. Centre of
      foot pressure (CoP) and trunk tilts in antero-posterior (AP) direction were
      measured during stance by two accelerometers on the upper and the lower trunk
      level. Subjects performed four series of eight trials lasted 20s: vibration with
      eyes open and closed, visual scene motion forward or backward, vibration together
      with scene motion forward or backward, scene motion forward or backward 3s before
      vibration. The results showed that early velocities and final angles of body tilt
      induced by soleus muscle vibration were modified by motion of visual scene. Early
      part of postural responses was changed slightly if sensory stimulation starts
      together. When visual stimulation started 3s before muscle vibration, the induced
      early CoP and trunk tilt records of postural response to vibration occurred with
      the faster slope similar for both directions of scene motion and for condition of
      vibration alone with eyes closed. Significantly different final CoP shifts and
      trunk angles were measured between condition with visual scene motion forward and
      backward. The effect of visual input on posture control was two times enhanced in
      paired sensory stimulation. The results indicated an important influence of
      unstable visual field on posture response to somatosensory stimulation where the
      early part of postural reaction indicated absence of visual influence.

PMID- 16621565
TI  - The influence of gait speed on local dynamic stability of walking.
AB  - The focus of this study was to examine the role of walking velocity in stability
      during normal gait. Local dynamic stability was quantified through the use of
      maximum finite-time Lyapunov exponents, lambda(Max). These quantify the rate of
      attenuation of kinematic variability of joint angle data recorded as subjects
      walked on a motorized treadmill at 20%, 40%, 60%, and 80% of the Froude velocity.
      A monotonic trend between lambda(Max) and walking velocity was observed with
      smaller lambda(Max) at slower walking velocities. Smaller lambda(Max) indicates
      more stable walking dynamics. This trend was evident whether stride duration
      variability remained or was removed by time normalizing the data. This suggests
      that slower walking velocities lead to increases in stability. These results may
      reveal more detailed information on the behavior of the neuro-controller than
      variability-based analyses alone.

PMID- 16621567
TI  - Age-related part taken by attentional cognitive processes in standing postural
      control in a dual-task context.
AB  - The aim of this work was to determine the effects of ageing on the possible
      mobilisation of cognitive processes in orthostatic postural balance. Seventy-nine
      individuals of three different age groups were placed in dual-task situations
      that combined standing postural control with three different cognitive tasks. Two
      of these three tasks, auditory-verbal and visual-verbal ones, required external
      information acquisition whereas the third, a mental counting task, did not
      require such information. The results showed contrasting variations in postural
      control performances that are an improvement in young subjects during cognitive
      tasks which required external information acquisition and a deterioration in
      elderly subjects during cognitive tasks which did not involve external
      information acquisition. The middle-aged subjects tended to develop these two
      types of variations simultaneously. These results confirm that cognitive
      processes could have a role that increases with age in ensuring postural control.
      The contrasting results observed between the young and old populations highlight
      that the allocation of cognitive resources to postural control could, on the one
      hand, contribute to improving postural performance in subjects with mainly
      automated control and, on the other, perturb this performance in subjects with
      mainly cognitive control.

PMID- 16621568
TI  - Foot models for clinical gait analysis.

PMID- 16621569
TI  - Effect of feet hyperpronation on pelvic alignment in a standing position.
AB  - Hyperpronation may cause malalignment of the lower extremity, frequently leading
      to structural and functional deficits both in standing and walking. Our aim was
      to study the effect of induced foot hyperpronation on pelvic and lower limb
      alignment while standing. Thirty-five healthy subjects were requested to remain
      in a natural standing position for 20s in four different modes: feet flat on the
      floor, and on wedges angled at 10 degrees, 15 degrees and 20 degrees, designed to
      induce hyperpronation. Sequencing was random, repeated three times and captured
      by eight computerized cameras using the VICON three-dimensional motion analysis
      system. We found that standing on the wedges at various angles, induced
      hyperpronation, with 41% to 90% of the changes attributable to the intervention.
      In addition, a statistically significant increase (paired t-test) in internal
      shank rotation (p<0.0001), internal hip rotation (p<0.0001) and anterior pelvic
      tilt (p<0.0001) was identified. A strong correlation was found between segmental
      alignment in every two consecutive modes at all levels (r=0.612-0.985; p<0.0001).
      These findings suggest that alignment of the lower extremity up to the pelvic
      girdle, can be altered, due to forces acting on the foot. Interaction between the
      foot and pelvis occurs in a kinematic chain reaction manner. Although this study
      was limited to healthy subjects, clinicians should be aware that when addressing
      pelvis and lower back dysfunction, foot alignment should be examined as a
      contributing factor.

PMID- 16621570
TI  - Why is metabolic labour divided in nitrification?
AB  - Winogradsky discovered in 1890 that nitrification is carried out in two
      consecutive steps by two distinct groups of bacteria: ammonia-oxidizing bacteria
      and nitrite-oxidizing bacteria. An explanation for this division of labour is
      offered based on the kinetic theory of optimal design of metabolic pathways,
      which postulates the existence of an optimal length for a pathway that maximizes
      the rate of ATP production. Shortening long pathways could, therefore, increase
      growth rate. However, this would reduce growth yield if the shorter pathway has
      fewer ATP-generating steps. High yields would be advantageous when bacteria grow
      in clonal clusters, as is typical for biofilms. It is postulated that bacteria
      that completely oxidize ammonia to nitrate exist in such environments.

PMID- 16621571
TI  - Structure-activity studies of a novel series of 5,6-fused heteroaromatic ureas as
      TRPV1 antagonists.
AB  - Novel 5,6-fused heteroaromatic ureas were synthesized and evaluated for their
      activity as TRPV1 antagonists. It was found that 4-aminoindoles and indazoles are
      the preferential cores for the attachment of ureas. Bulky electron-withdrawing
      groups in the para-position of the aromatic ring of the urea substituents
      imparted the best in vitro potency at TRPV1. The most potent derivatives were
      assessed in in vivo inflammatory and neuropathic pain models. Compound 46,
      containing the indazole core and a 3,4-dichlorophenyl group appended to it via a
      urea linker, demonstrated in vivo analgesic activity upon oral administration.
      This derivative also showed selectivity versus other receptors in the CEREP
      screen and exhibited acceptable cardiovascular safety at levels exceeding the
      therapeutic dose.

PMID- 16621572
TI  - A new structural theme in C2-symmetric HIV-1 protease inhibitors: ortho
      substituted P1/P1' side chains.
AB  - In this report, the rapid syntheses of 24 novel C2-symmetric HIV-1 protease
      inhibitors are described. Two ortho-iodobenzyloxy containing C-terminal
      duplicated inhibitors served as starting materials for microwave-enhanced
      palladium(0)-catalyzed carbon-carbon bond forming reactions (Suzuki, Sonogashira,
      Heck, and Negishi). Highly potent inhibitors equipped with ortho-functionalized
      P1/P1' side chains as the structural theme were identified. Computational efforts
      were applied to study the binding mode of this class of inhibitors and to
      establish structure-activity relationships. The overall orientation of the
      inhibitors in the active site was reproduced by docking which suggested three
      possible conformations of the P1/P1' groups of which two seem more plausible.

PMID- 16621573
TI  - Synthesis and biological evaluation of novel PDMP analogues.
AB  - A new series of hybrid PDMP analogues, based both on PDMP and styryl analogues of
      natural ceramide, has been synthesized from D-serine. The synthetic route was
      developed such that future introduction of different aryl groups is
      straightforward. Biological evaluation, both in vitro on rat liver Golgi
      fractions as well as in HEK-293 and COS-7 cells, revealed two lead compounds with
      comparable inhibitory potency as PDMP, which could be elaborated to more potent
      inhibitors.

PMID- 16621574
TI  - Dose-dependent antithrombotic activity of an orally active tissue factor/factor
      VIIa inhibitor without concomitant enhancement of bleeding propensity.
AB  - The discovery of a highly potent and selective tissue factor/factor VIIa
      inhibitor is described. Upon oral administration of its double prodrug in the
      guinea pig, a dose-dependent antithrombotic effect is observed in an established
      model of arterial thrombosis without prolonging bleeding time. The
      pharmacodynamic properties of this selective inhibitor are compared to the
      behaviour of a mixed factor VIIa/factor Xa inhibitor.

PMID- 16621575
TI  - Closing in on the AMPA receptor: synthesis and evaluation of 2-acetyl-1-(4'
      chlorophenyl)-6-methoxy-7-[11C]methoxy-1,2,3,4-tetrahydroisoquinoline as a
      potential PET tracer.
AB  - 2-Acetyl-1-(4'-chlorophenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline, one of
      the most potent non-competitive AMPA antagonists described to date, has been
      labelled with carbon-11 and tritium and evaluated as a potential ligand for in
      vivo imaging of AMPA receptors using PET. The carbon-11 labelled compound showed
      good initial brain uptake in rats, but with rapid clearance and relatively
      homogenous distribution. In saturation binding studies, the tritiated racemic
      ligand was found to be highly potent with a Kd of 14.8+/-1.8 nM. We conclude that
      the low receptor density labelled with this compound, its rapid clearance from
      the CNS and low specific binding makes it unsuitable as an in vivo PET imaging
      agent for AMPA receptors.

PMID- 16621576
TI  - Anticonvulsant evaluation and mechanism of action of benzylamino enaminones.
AB  - The mechanism of anticonvulsant action was evaluated for the benzylamino
      enaminones. The most potent enaminone in this series was the unsubstituted
      benzylamine analog (30; methyl 4-benzylamino-6-methyl-2-oxocyclohex-3-en-1-oate)
      which had an oral effective dose (ED50) in rats of 27 mg/kg against maximal
      electroshock seizures, and a concentration 10-fold less than this dose depressed
      excitatory synaptic transmission, and action potential firing in the rat brain in
      vitro.

PMID- 16621577
TI  - Immobilized methyltrioxo rhenium (MTO)/H2O2 systems for the oxidation of lignin
      and lignin model compounds.
AB  - A convenient and efficient application of heterogeneous methylrhenium trioxide
      (MTO) systems for the selective oxidation of lignin model compounds and lignins
      is reported. Environmental friendly and low-cost H2O2 was used as the oxygen atom
      donor. Overall, the data presented and discussed in this paper point toward the
      conclusion that the immobilized heterogeneous catalytic systems based on H2O2/and
      MTO catalysts are able to extensively oxidize both phenolic and non-phenolic,
      monomeric, and dimeric, lignin model compounds. Condensed diphenylmethane models
      were found also extensively oxidized. Technical lignins, such as hydrolytic sugar
      cane lignin (SCL) and red spruce kraft lignin (RSL), displayed oxidative activity
      with immobilized MTO catalytic systems. After oxidation, these lignins displayed
      the formation of more soluble lignin fragments with a high degree of degradation
      as indicated by the lower contents of aliphatic and condensed OH groups, and the
      higher amounts of carboxylic acid moieties. Our data indicate that immobilized
      MTO catalytic systems are significant potential candidates for the development of
      alternative totally chlorine-free delignification processes and environmental
      sustainable lignin selective modification reactions.

PMID- 16621578
TI  - Design and synthesis of novel metalloproteinase inhibitors.
AB  - A series of N-benzoyl 4-aminobutyric acid hydroxamate analogs were synthesized
      and evaluated as matrix metalloproteinase inhibitors. Synthetic work was focused
      on the chemical modification of the 4-aminobutyric acid part using easily
      available starting materials. As such, chemical modification was carried out
      using commercially available starting materials such as 4-aminobutyric acid, (+)-
      and (-)-malic acid, and D- and L-glutamic acid derivatives. Among the compounds
      tested, N-[4-(benzofuran-2-yl)benzoyl] 4-amino-4S-hydroxymethylbutyric acid
      hydroxamates derived from L-glutamic acid demonstrated more potent inhibitory
      activity against MMP-2 and MMP-9 compared with the corresponding 2S-hydroxy
      analogs or 3S-hydroxy analogs, respectively, which were derived from (-)-malic
      acid. Structure-activity relationship study is presented.

PMID- 16621579
TI  - Comment on "Investigation on optical properties of ZnO nanowires by electron
      energy-loss spectroscopy".
AB  - Recently, Zhang et al. have published a paper [Zhang, Z.H., Qi, X.Y., Jian, J.K.,
      Duan, X.F., 2006. Micron 37, 229-233] in which - among others - the determination
      of the optical properties of a semiconductor by use of electron energy-loss
      spectroscopy (EELS) is performed with 200 keV electrons and a collection angle of
      only 0.3 mrad. The authors do not take into account relativistic effects such as
      Cerenkov losses (CL) before performing Kramers-Kronig Analysis (KKA) on the EELS
      spectra obtaining erroneous results. Although the positions of features within
      the optical properties are consistant with the simulated ones, the relative
      hights or absolute values differ a lot.

PMID- 16621580
TI  - Structure of mammalian spermatozoa in respect to viability, fertility and
      cryopreservation.
AB  - Morphological assessment of spermatozoa has a long history and it is generally
      accepted that specific morphologic structural deviations correlate with male sub-
      and infertility. Although many different and also new methods are used in semen
      analysis, light microscopy is still used for routine morphological evaluation.
      This paper gives an overview about the detailed structure of physiological
      mammalian spermatozoa as well as the most common morphological deviations in
      correlation to fertility. This should be the basis for explanation of problems
      resulting from semen cryopreservation. General aspects of semen cryopreservation
      should be regarded before to facilitate the understanding of methods and
      mechanisms.

PMID- 16621581
TI  - Activity measurements and determination of gamma-ray emission intensities in the
      decay of 65Zn.
AB  - An International EUROMET exercise, Action 721, was organized with the objective
      of obtaining more reliable decay data on the disintegration of 65Zn. Nine
      laboratories participated, sending their results relating to activity
      measurements and 1115-keV gamma-ray emission intensity. Participants mainly used
      the 4pibeta-gamma coincidence method for the activity measurement, the resulting
      values and uncertainty budgets are described. New gamma-ray emission intensities
      were also measured in this exercise and, taking into account previously published
      values, the intensity of the 1115-keV gamma-ray emission has been determined to
      be 50.22(11)%.

PMID- 16621582
TI  - Improved determination of plutonium content and isotopic ratios in low activity
      samples by alpha-particle and underground L X-ray measurement.
AB  - The determination of the isotopic ratio of 239Pu and 240Pu by alpha-particle
      spectrometry is limited due to the small differences in the alpha-particle
      energies. But taking into account the differences in the L X-ray emission
      probabilities of the two plutonium isotopes, an additional L X-ray measurement
      allows the isotopic ratio of 239Pu and 240Pu to be determined. The sensitivity of
      this method can be improved, as described in this work, by performing the L X-ray
      measurement in an underground laboratory.

PMID- 16621583
TI  - Quality control of liquid scintillation counters.
AB  - Liquid scintillation counting (LSC) is widely used at LNHB for primary
      standardization of radionuclides (TDCR method), for secondary calibration and
      also for source stability studies or radioactive purity measurements. A total of
      five LSC counters are used for these purposes: two locally developed 3
      photodetector counters for the implementation of the TDCR method, two Wallac 1414
      counters and one Wallac 1220 Quantulus counter. The quality of the LSC
      measurements relies on the correct operation of these counters and their
      traceability to the frequency and time units.

PMID- 16621584
TI  - Standardization and decay data determinations of 125I, 54Mn and 203Hg.
AB  - The absolute 4pi-betagamma coincidence counting has been used to measure the
      activity concentrations of 54Mn and 203Hg, and the Sum-Peak method was used for
      125I. 54Mn and 125I radionuclides have been part of international key-comparisons
      coordinated by the Bureau International des Poids et Measures (BIPM) in
      2003/2004, while 203Hg is part of the traceability programme of the National
      Laboratory for Ionizing Radiation Metrology (LNMRI)/Brazil. Three different
      detectors were used for the Sum-Peak method: 3''x3'' NaI(Tl) and 5''x5'' well
      NaI(Tl) scintillation detectors and a planar germanium detector. Direct
      measurements were made of the photon emission probabilities of the 35.5-, 834.8-
      and 279.2-keV gamma-rays of 125I, 54Mn and 203Hg to give values of (0.0667+/
      0.0014), (0.9997+/-0.0055) and (0.8161+/-0.0005), respectively. The half-lives of
      203Hg and 54Mn were also determined by means of a 4pigamma ionization chamber
      (203Hg) and by the reference source method using a HPGe detector (54Mn) to give
      values of (46.639+/-0.023) days and (312.1+/-0.9) days, respectively.

PMID- 16621585
TI  - Blindness after Le Fort I osteotomy: a possible complication associated with
      pterygomaxillary separation.
AB  - INTRODUCTION: Visual loss after Le Fort I osteotomy is a devastating complication
      the mechanism of which is not always clear. METHODS: A case report of blindness
      following Le Fort I osteotomy is presented. The literature on the various skull
      base complications associated with Le Fort I osteotomies is reviewed and the
      mechanisms of these complications discussed. CONCLUSION: The radiological
      findings in this case are similar to those previously reported. They strongly
      support the hypothesis that an adverse transmission of forces associated with
      pterygomaxillary separation via the sphenoid bone to the intra- and extracranial
      portions of the skull base is the main reason for injury to the optic and other
      cranial nerves as well as to the branches of the carotid artery.

PMID- 16621586
TI  - Open versus arthroscopic surgery for internal derangement of the
      temporomandibular joint: a retrospective study comparing two centres' results
      using the Jaw Pain and Function Questionnaire.
AB  - OBJECTIVES: Surgical procedures currently used for treating of internal
      derangement of the temporomandibular joint vary widely. Although different
      studies present favourable results following open or arthroscopic TMJ surgery,
      the criteria for a successful treatment outcome are not always defined
      identically. In a retrospective study, two groups of patients who underwent
      either open or arthroscopic surgery for internal derangement (stages III-V
      according to Wilkes' classification) were investigated using the so-called JPF
      Questionnaire. PATIENTS AND METHODS: The Kyoto collective (group 1) consisted of
      28 patients, 2 men and 26 women, who underwent arthroscopic surgery. At the time
      of surgery, age ranged from 13 to 77 years (mean 32.8 y). The postoperative
      follow-up period ranged from 4 years and 4 months to 5 years and 9 months. Twelve
      of the 28 patients were classified as stage III, 10 as stage IV and 6 were
      classified as stage V (according to Wilkes) at the time of surgery. The Vienna
      collective (group 2) also consisted of 28 patients, 2 men and 26 women, who
      underwent open meniscoplasty or discectomy. At the time of surgery age ranged
      from 17 to 55 years (mean 31.6 years). The postoperative follow-up ranged from 5
      to 6 years and 9 months. Fourteen of the 28 patients were classified as stage
      III, 11 as stage IV and 3 were classified as stage V (according to Wilkes) at the
      time of surgery. The results of the JPF-Questionnaire of the two groups were
      compared by Wilcoxon 2-sample tests. The Japanese version was applied, while in
      Austria the German version of this questionnaire was applied. RESULTS: At a level
      of significance alpha=0.05 no significant difference was found when comparing the
      subgroups (Wilkes stages III, IV and V) or both groups of patients 5 years after
      temporomandibular joint surgery. CONCLUSION: There cannot be any clear indication
      for only one of the treatment modalities as similar results were noted following
      open or arthroscopic temporomandibular joint surgery. Nevertheless, arthroscopic
      surgery is a minimally invasive procedure resulting in a shorter or no time of
      hospitalization when compared with open surgery and therefore is preferred by
      many surgeons nowadays.

PMID- 16621587
TI  - Cross-cultural adaptation of the JPF-Questionnaire for German-speaking patients
      with functional temporomandibular joint disorders.
AB  - OBJECTIVES: Clinical research related to the management of the syndrome of
      temporomandibular joint pain and dysfunction would be facilitated enormously
      between researchers in different locations around the world if a small number of
      patient-oriented questionnaires were to achieve wide acceptance. It would make
      comparison of therapeutic results possible. For this reason, a cross-cultural
      version of the Jaw Pain and Function (JPF)-Questionnaire was developed and
      validated for use in German-speaking patients with functional temporomandibular
      disorders. MATERIAL AND METHODS: The scale was translated from the English into
      the German language and translated back into English again, pretested and
      reviewed by a committee. The German version of the JPF-Questionnaire was tested
      on 137 patients with temporomandibular disorders. Reliability and concurrent
      construct validity were assessed using Pearson's correlation coefficients.
      RESULTS: The concurrent validity was assessed by evaluating the relation of the
      questionnaire's summary score (the internal criterion) to data on maximum
      interincisal distance (the external criterion). Spearman's and correlation
      coefficients were statistically significant for the comparison of the summary
      score with maximal mouth opening (r=-0.213; p=0.036). Test-retest reliability for
      the JPF-Questionnaire was also assessed by Spearman's correlation coefficients:
      at first admission at the clinic (time a, mean=20.23+/-16.42, median=16), then at
      the time of administration 1 day later at home (time b, mean=17.98+/-16.29,
      median=13), and 7 days later at home (time c, mean=17.90+/-15.77, median=13).
      They were r=0.91 (p=0.0001) for the initial administration with the repetition 1
      day later, r=0.90 (p=0.0001) for the initial administration with the repetition 1
      week later, and r=0.93 (p=0.0001) for the correlation between the two
      repetitions. Test - retest reliability measured by mean-against-difference graphs
      was not satisfactory for time (a) versus time (b) and time (a) versus time (c)
      but there was a good test-retest reliability for time (b) versus time (c).
      CONCLUSION: The use of this instrument can be recommended in future clinical
      trials, as the German version of the JPF-Questionnaire seems to be valid and-
      under the same test-retest conditions--reliable for the assessment of
      temporomandibular joint disorders.

PMID- 16621588
TI  - Safrole-induced cellular Ca2+ increases and death in human osteosarcoma cells.
AB  - The effect of the carcinogen safrole on intracellular Ca2+ movement has not been
      explored in osteoblast-like cells. This study examined whether safrole could
      alter Ca2+ handling and viability in MG63 human osteosarcoma cells. Cytosolic
      free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as
      a fluorescent Ca2+ probe. Safrole at concentrations above 130 microM increased
      [Ca2+]i in a concentration-dependent manner with an EC50 value of 450 microM. The
      Ca2+ signal was reduced by 30% by removing extracellular Ca2+. Addition of Ca2+
      after safrole had depleted intracellular Ca2+ induced Ca2+ influx, suggesting
      that safrole caused Ca2+ entry. In Ca2+-free medium, after pretreatment with 650
      microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump
      inhibitor) failed to release more Ca2+; and pretreatment with thapsigargin
      inhibited most of the safrole-induced [Ca2+]i increases. Inhibition of
      phospholipase C with U73122 did not affect safrole-induced Ca2+ release; whereas
      activation of protein kinase C with phorbol ester enhanced safrole-induced
      [Ca2+]i increase. Trypan exclusion assays revealed that incubation with 65 microM
      safrole for 30 min did not kill cells, but incubation with 650 microM safrole for
      10-30 min nearly killed all cells. Flow cytometry demonstrated that safrole
      evoked apoptosis in a concentration-dependent manner. Safrole-induced
      cytotoxicity was not reversed by chelation of Ca2+ with BAPTA. Collectively, the
      data suggest that in MG63 cells, safrole induced a [Ca2+]i increase by causing
      Ca2+ release mainly from the endoplasmic reticulum in a phospholipase C
      independent manner. The safrole response involved Ca2+ influx and is modulated by
      protein kinase C. Furthermore, safrole can cause apoptosis in a Ca2+-independent
      manner.

PMID- 16621589
TI  - Hypolipidemic therapy for the metabolic syndrome.
AB  - The metabolic syndrome appears to affect a significant proportion of the
      population and is associated with increased risk for development of
      cardiovascular disease as well as of type-2 diabetes. No single treatment for the
      metabolic syndrome as a whole yet exists. While the primary management of
      patients with the metabolic syndrome involves healthy lifestyle promotion, the
      atherogenic dyslipidemia is a primary target for cardiovascular disease risk
      reduction in these patients. Statin therapy provides effective reduction of LDL
      cholesterol, which represents the primary therapeutic goal of lipid-lowering
      therapy in patients at risk for cardiovascular disease. Fibrates in turn are
      effective in normalizing lipid levels (mainly triglycerides and HDL-cholesterol)
      in patients with the metabolic syndrome and may improve insulin resistance.
      Whereas statins remain the drug of choice for patients who need to achieve the
      LDL-cholesterol goal, fibrate therapy may represent an alternative for those with
      low HDL-cholesterol and high triglyceride levels. The simultaneous use of
      fibrates could be indicated in patients whose LDL-cholesterol is controlled by
      statin therapy but whose HDL-cholesterol and/or triglycerides are still
      inappropriate. Such a combination, however, needs careful monitoring due to the
      potential hazard of adverse drug interactions. Nicotinic acid and ezetimibe may
      be useful agents for therapy, particularly when combined with statins. A number
      of emerging therapies offer potential as future options for the pharmacological
      treatment of metabolic syndrome.

PMID- 16621590
TI  - Therapeutic effects of I(f) blockade: evidence and perspective.
AB  - Heart rate slowing has been accepted for decades as a primary therapeutic
      approach to prevention (and even to treatment) of angina pectoris. Pure heart
      rate slowing has not been achieved with previously available rate-slowing
      pharmacological agents (beta adrenergic blockers, certain calcium channel
      blockers), all of which have other pharmacological effects that may be beneficial
      but also may underlie adverse drug effects. Modulation of heart rate is a
      function of variation in the I(f) current, a sodium-potassium mediated membrane
      phenomenon that is active physiologically only in the heart's sinoatrial node.
      Though the current first was described more than 25 years ago, a practical
      pharmacological method for its inhibition only recently has been developed,
      tested and approved for use in Europe. The effective drug, ivabradine, has
      demonstrated anti-anginal, anti-ischemic efficacy and now is being tested for its
      effect on survival in patients with coronary artery disease and impaired left
      ventricular function, as well as for heart failure. The data supporting the use
      of the drug for angina prevention, and the potential for additional applications,
      are reviewed in this article.

PMID- 16621592
TI  - I(f) and the biological pacemaker.
AB  - A biological pacemaker based on the HCN gene family, the molecular correlate of
      the native cardiac pacemaker current, holds promise of enhancing or supplanting
      current electronic pacemakers by providing autonomic responsiveness of cardiac
      rate. Gene-based and cell-based delivery of the HCN gene have been employed to
      produce biological pacemakers. This article reviews efforts to date to create
      gene- and cell-based biological pacemakers, using both the HCN gene family and
      other approaches, and discusses what is known about the autonomic responsiveness
      in each case. Possible future refinements to an HCN based biological pacemaker
      also are discussed.

PMID- 16621593
TI  - Oleic acid enhances vascular smooth muscle cell proliferation via
      phosphatidylinositol 3-kinase/Akt signaling pathway.
AB  - Nonesterified fatty acids are acutely liberated during lipolysis and are
      chronically elevated in pathological conditions such as insulin resistance,
      hypertension, and obesity, which are known risk factors for atherosclerosis. The
      present study was designed to investigate the effects of oleic acid (OA), an 18
      carbon cis-monosaturated fatty acid on proliferation of vascular smooth muscle
      cells (VSMC). Incubation of a rat VSMC (A10 cells) with OA (50 microM) resulted
      in an increase of cells entering the S phase of the cell cycle. In consistent
      with the effects on cell cycle distribution, OA stimulated VSMC proliferation in
      a dose-dependent manner. The mitogenic effect of OA was significantly reduced by
      pretreatment of LY294002 (5 microM) or wortmannin (1 microM), potent, and
      specific inhibitors of phosphatidylinositol 3-kinase (PI3K). OA also induced
      activation of Akt/protein kinase B (PKB) in a time-dependent manner. OA-induced
      activation of Akt/PKB was inhibited by either LY294002 or wortmannin. Taken
      together, these experiments show that the enhanced phosphorylation of Akt/PKB by
      OA is dependent on PI3K and suggest that this signaling event may be important
      for the regulation of OA-induced VSMC proliferation.

PMID- 16621594
TI  - Developments in the production and quality control of poliovirus vaccines --
      historical perspectives.
AB  - Using virus grown in monkey kidney cells, Salk and his colleagues developed an
      inactivated poliovirus vaccine (IPV) in 1952. A large-scale field trial showed
      the vaccine to be safe and highly immunogenic in children, but soon after the
      vaccine became generally available in 1955, cases of paralytic disease were
      reported in recipients. Investigations showed that almost all the cases occurred
      in children who had received vaccine from one particular manufacturer. Extensive
      studies attributed the disaster to problems with inactivation. Addition of a
      Seitz filtration step midway during formalin inactivation and extension of the
      inactivation period resulted in a safe vaccine. No further paralytic cases were
      observed following the use of several hundred million doses of this improved
      vaccine. Thus, IPV was safe and caused a dramatic decline in the incidence of
      poliomyelitis in countries where it was used. A second generation IPV is produced
      in fermentors using well-characterized cell strains or continuous cell lines. The
      major breakthrough in the development of live poliovirus vaccine was the
      application of tissue culture methods for virus attenuation. By 1959 several
      candidate live oral poliovirus vaccines (OPV) had been developed. These were
      clinically tested in millions of individuals and found to be safe and effective.
      Since the attenuated virus strains developed by Koprowski and Cox were more
      neurotropic in monkeys than the Sabin strains, only the latter was licensed in
      the USA in 1961 and endorsed shortly after by the World Health Organization
      (WHO). The widespread use of Sabin's OPV in many countries hastened the
      development of International Requirements by WHO for OPV in 1962 to define the
      criteria that ensured the uniformity of batches produced by different
      manufacturers. These have been updated continuously in light of new information
      and quality control procedures. Extensive field trials have shown the risk of OPV
      associated polio to be less than 0.3 per million doses administered.

PMID- 16621595
TI  - Bacterial expression of functional, biotinylated peripheral cannabinoid receptor
      CB2.
AB  - A biotin-protein ligase recognition site (BRS) was inserted into a polypeptide
      comprised of the maltose-binding protein, the peripheral cannabinoid receptor
      (CB2), thioredoxin A, and a polyhistidine tag at the carboxy terminus. Expression
      levels of the recombinant receptor in Escherichia coli BL21(DE3) cells were
      approximately 1mg per liter of bacterial culture. The biotinylated CB2-fusion
      fully retained its ligand-binding capacity. Introduction of the BRS at the C
      terminus of the CB2 fusion protein (construct CB2-109) resulted in its complete
      in vivo biotinylation; the biotinylated protein was streptavidin-binding
      competent. Positioning of the BRS near the N-terminus of CB2 (CB2-112) resulted
      in a very low level of biotinylation in vivo. However, the detergent solubilized
      and purified CB2-112 fusion protein were successfully biotinylated in vitro by
      action of a BirA biotin-protein ligase. The biotinylated CB2-112 fusion protein
      was cleaved by the tobacco etch virus protease at specifically inserted sites,
      and deposited onto monomeric avidin agarose beads. Biotinylation of the
      recombinant CB2 receptor enabled not only purification but also immobilization of
      the GPCR on a solid support in homogeneous orientation which is beneficial for
      subsequent structural characterization.

PMID- 16621596
TI  - Estimation of bias in nongenetic observational studies using "mendelian
      triangulation".
AB  - PURPOSE: Phenotype-disease odds ratios calculated from the effect of a genotype
      on its phenotype and on disease risk ("Mendelian triangulation") can be used as a
      standard to assess bias on the corresponding odds ratio from nongenetic studies.
      Statistical tests are commonly used to compare these odds ratios. We propose a
      method to estimate the magnitude of the bias and judge the validity of the
      phenotype-disease association. METHODS: For four published examples, we obtained
      10,000 random values from distributions of the odds ratios from both genetic and
      nongenetic studies. A range of values compatible with an unbiased odds ratio was
      then calculated from the empirical distribution of the differences between both
      odds ratios. RESULTS: We show that estimating a range of likely values for an
      unbiased odds ratio is useful to judge the effect of the phenotype and identify
      cases for which information from genetic studies adds little to the evaluation of
      the phenotype-disease association. Conversely, statistical tests could be
      misleading. CONCLUSIONS: Estimating a range of values for an unbiased odds ratio
      is more informative and appropriate than statistical tests when using the
      Mendelian triangulation approach for assessment of bias in phenotype-disease
      association studies.

PMID- 16621597
TI  - Participants who left a multiple-wave cohort study had similar baseline
      characteristics to participants who returned.
AB  - PURPOSE: Research on determinants of an individual's pattern of response,
      considered as a profile across time, for cohort studies with multiple waves is
      limited. In this prospective population-based pregnancy cohort, we investigated
      baseline characteristics of participants after partitioning them according to
      their history of response to different interview waves. METHODS: Data are from
      the Mater-University of Queensland Study of Pregnancy 1981 to 1983 cohort,
      Brisbane, Australia. Complete baseline information was collected for 7223 of 7535
      eligible individuals (95.9%). Follow-up occurred at 6 months, 5 years, and 14
      years. Response rates were 93.0%, 72.5%, and 71.8%. Participants were allowed to
      leave and reenter the study. Participants were categorized as always,
      intermittent, or never responders. Intermittent responders were categorized
      further as leavers (responded at least once before leaving the study) or
      returners (left the study before reentering). RESULTS: Participants who always
      responded were older, more educated, married, Caucasian, and nonsmokers and had
      higher incomes. Intermittent responders shared similar baseline characteristics.
      Relative risk for being an intermittent responder was located between risks for
      always or never responding. CONCLUSIONS: Participants who left and reentered the
      study had baseline characteristics similar to participants who responded at least
      once and then left the study.

PMID- 16621598
TI  - The validity of the certification of manner of death by Ontario coroners.
AB  - PURPOSE: The aim of the study is to examine the validity of manner of death (MOD)
      certification of unnatural adult deaths by Ontario coroners. METHODS: A census of
      306 active coroners practicing in Ontario was performed, with data collection
      occurring in 2002. Mailed self-administered questionnaires contained 14
      fictitious clinicopathologic scenarios and questions regarding demographic
      information of the coroner. Crude and adjusted odds ratios of correct MOD
      certification were calculated by using responses of two deputy chief coroners as
      the gold standard. RESULTS: Nearly 74% of coroners responded to the survey.
      Deaths from hanging, drowning, and carbon monoxide had better odds of being
      certified correctly; whereas deaths from heroin, over-the-counter medication, and
      injuries from a descent had decreased odds of being certified correctly.
      Scenarios including a prior suicide attempt or a note had greater odds of correct
      MOD certification than those with only depression. Accidental deaths were
      underreported when injury resulted in a "natural" lethal complication and when
      there was a delay between injury and death. CONCLUSIONS: In detailing which
      deaths are likely to be misclassified and how they may be misclassified, this
      study will allow future research to more accurately assess suicidal and
      accidental deaths.

PMID- 16621599
TI  - Induced abortion: not an independent risk factor for pregnancy outcome, but a
      challenge for health counseling.
AB  - PURPOSE: Low birth weight (LBW), preterm births, abnormal placentation, and
      miscarriages have been associated with prior induced abortions. An incidence
      related effect has been suggested. The objective of this study is to assess the
      effects of prior induced abortions on obstetric risk factors and pregnancy
      outcome in conditions of free high-standard maternity care used by almost the
      entire pregnant population in Finland. METHODS: We analyzed a population-based
      database including 26,976 singleton pregnancies from 1989 to 2001, of which 2364
      were among women with one prior induced abortion and 355 women had had at least
      two prior induced abortions. Data included maternal risk factors, pregnancy
      characteristics, and obstetric outcome measures and were based on results of a
      self-administered questionnaire at 20 weeks of pregnancy and clinical records.
      Odds ratios (ORs) concerning pregnancy outcomes were calculated in multiple
      logistic regression analysis. RESULTS: Induced abortions were associated with
      several known pregnancy risk factors; specifically, maternal age older than 35
      years, unemployment, unmarried status, low educational level, smoking, alcohol
      consumption, overweight condition, and chronic illnesses. Preterm birth (OR,
      1.19; 95% confidence interval, 1.01-1.41) in women with one prior abortion (7.3%
      versus 6.2%) and LBW (OR, 1.54; 95% confidence interval, 1.02-2.32) in women with
      two or more prior abortions (7.0% versus 4.7%) appeared to be more common, but
      after logistic regression analysis, we found no evidence of adverse pregnancy
      outcomes. CONCLUSIONS: Induced abortion is not an independent risk factor for
      adverse obstetric outcome. Marked health behavioral pregnancy risks are
      associated with prior induced abortions. Health counseling of these women is a
      challenge, but this objective has not yet been achieved.

PMID- 16621600
TI  - Mutational analysis of the functional motifs in the ATPase domain of
      Caenorhabditis elegans fidgetin homologue FIGL-1: firm evidence for an
      intersubunit catalysis mechanism of ATP hydrolysis by AAA ATPases.
AB  - The AAA family proteins usually form a hexameric ring structure. The ATP-binding
      pocket, which is located at the interface of subunits in the hexamer, consists of
      three functionally important motifs, the Walker A and B motifs, and the second
      region of homology (SRH). It is well known that Walker A and B motifs mediate ATP
      binding and hydrolysis, respectively. Highly conserved arginine residues in the
      SRH have been proposed to function as arginine fingers, which interact with the
      gamma-phosphate of bound ATP. To elucidate the mechanism of ATP hydrolysis, we
      prepared several mutants of the Caenorhabditis elegans fidgetin homologue FIGL-1
      carrying a mutation in each of the above-mentioned three motifs. None of the
      constructed mutants showed ATPase activity. All the mutants except for K362A were
      able to bind ATP. A decrease in the ATPase activity by mixing wild-type and each
      mutant subunits was caused by the formation of hetero-hexamers. Mixtures of E416A
      and R471A, or N461A and R471A led to the formation of hetero-hexamers with
      partially restored ATPase activities, providing direct, firm evidence for the
      intersubunit catalysis model. In addition, based on the results obtained with
      mixtures of K362A with wild-type or R471A subunits, we propose that a
      conformational change upon ATP binding is required for proper orientation of the
      arginine fingers, which is essential for efficient hydrolysis of ATP bound to the
      neighboring subunit.

PMID- 16621601
TI  - The three-dimensional structure of complex I from Yarrowia lipolytica: a highly
      dynamic enzyme.
AB  - The structure of complex I from Yarrowia lipolytica was determined by three
      dimensional electron microscopy. A random conical data set was collected from
      deep stain embedded particles. More than 14000 image pairs were analyzed. Through
      extensive classification combined with three-dimensional reconstruction, it was
      possible for the first time to show a much more detailed substructure of the
      complex. The peripheral arm is subdivided in at least six domains. The membrane
      arm shows two major protrusions on its matrix facing side and exhibits a channel
      like feature on the side facing the cytoplasm. Structures resembling a tether
      connecting the subunits near the catalytic center with the protrusions of the
      membrane arm provide a second connection between matrix and membrane domain.

PMID- 16621602
TI  - The Arabidopsis thaliana AAA protein CDC48A interacts in vivo with the somatic
      embryogenesis receptor-like kinase 1 receptor at the plasma membrane.
AB  - Fluorescent cell division cycle (CDC)48 proteins were studied in living plant
      protoplasts. CDC48A and somatic embryogenesis receptor like kinase 1 (SERK1) were
      found to co-localize in the endoplasmatic reticulum (ER) and at the plasma
      membrane (PM), but not in endosomal compartments. Fluorescent lifetime imaging
      microscopy (FLIM) was used to detect Forster resonance energy transfer (FRET)
      between CrFP/YFP-tagged CDC48A and SERK1. FRET is indicative of direct protein
      protein interaction. CDC48A was found to interact only with SERK1 in small areas
      at the PM, but not in endosomes. These findings confirm and extend our previous
      findings that CDC48A in plants directly interacts with SERK1.

PMID- 16621603
TI  - Intracellular distributions of essential elements in cardiomyocytes.
AB  - We describe the intracellular distributions of nine essential elements (P, S, Cl,
      K, Ca, Mn, Fe, Cu, and Zn) found in cardiomyocytes imaged using synchrotron X-ray
      induced fluorescence. Cardiomyocytes were isolated from rat hearts, flash frozen
      on Si(3)N(4) windows, freeze-dried, and imaged with approximately 300 nm spatial
      resolution. Distinct longitudinal patterns in cardiomyocytes were most apparent
      for the elements Fe and Cu, which clearly colocalized. Transverse striations were
      apparent for P, S, Fe, and Zn, while those for Zn were consistently the most
      prominent ( approximately 10(-3)M) and appeared with a periodicity in the range
      1.63-1.75 microm, the expected length of a sarcomere. Transverse striations for
      high concentrations of P, Fe, and Zn and low concentrations of S colocalized and
      coincided with the I-band of the intact cardiomyocyte. Fluorescence microscopy
      using FluoZin-3 in intact cardiomyocytes suggests that Zn(2+) influx is through
      sarcolemmal calcium channels and that significant stores of intracellular Zn(2+)
      may be released quickly (<1s) into the cytosol. These data collectively suggest
      that Zn(2+) is buffered by structures associated near the T-tubules and/or in the
      sarcoplasmic reticulum and is found in relative abundance sufficient to act as a
      modifier of Ca(2+) regulation or as a possible signaling messenger for gene
      expression.

PMID- 16621604
TI  - Going through the motions: the ATPase cycle of p97.
AB  - p97 (VCP, Cdc48), a type II AAA+ ATPase family member, is ubiquitous, essential,
      highly abundant, and involved in a diverse range of biological functions with
      roles in membrane fusion, endoplasmic-reticulum associated degradation,
      transcriptional activation, and cell cycle control. As such, dysfunction of this
      protein has serious pathological consequences and has been implicated in a
      variety of cancers and neurodegenerative diseases. p97 has a large number of
      adaptor proteins through which it transmits energy from ATPase activity to
      conformational changes which are then exerted onto target proteins. p97 has been
      studied by a variety of biochemical and structural techniques at various
      resolutions and stages throughout its ATPase cycle. From these studies, many
      models have been proposed and consequently a single model for p97's action cannot
      be suggested. Many questions about the mechanism of p97 still remain, including
      whether the protomers act in a concerted manner and crucially how the induced
      changes in p97 are transmitted to its adaptor proteins and target substrates. The
      elucidation of p97's mechanism is not only important in furthering our knowledge
      of this intriguing protein and its many functions, but subsequently in the
      development of potential therapies for diseases associated with p97 dysfunction.

PMID- 16621605
TI  - Innate and adaptive immune responses of turbot, Scophthalmus maximus (L.),
      following experimental infection with Enteromyxum scophthalmi (Myxosporea:
      Myxozoa).
AB  - The innate and adaptive immune responses against Enteromyxum scophthalmi was
      studied in turbot (Scopthalmus maximus (L.)) experimentally exposed to the
      parasite by cohabitation. Haematological, histopathological, cellular and humoral
      factors were determined in samples taken from control (CTRL) and recipient (RCPT,
      naive fish cohabited with donor infected fish) animals at 0, 20, 29, 40 and 43
      days post exposure (p.e). Infection was first detected at day 20 p.e. and
      prevalence reached 100% at 40 days p.e, when first mortalities occurred. A
      significant reduction in weight and condition factor was found in RCPT, though no
      significant differences in haematocrit or serum protein levels were detected
      between CTRL and RCPT. Some immune effectors were clearly activated in RCPT: the
      percentage of circulating granulocytes was significantly increased, as well as
      the number of blood cells positive in the respiratory burst assay; leucocyte
      infiltration in intestine was found mainly on days 20 and 29 p.e.; total serum
      antiproteases and alpha-2-macroglobulin levels were higher in most of the
      samplings, with significant differences on the last sampling. Other effectors
      were clearly down regulated in RCPT: haematopoietic depletion appeared in head
      kidney from day 29 p.e. onwards, and the number of apoptotic cells and MMC
      increased in head kidney and spleen; the percentage of lymphocytes decreased
      progressively and significantly; a clear, but not statistically significant, drop
      in serum complement was registered at 40 days p.e.; also, a significant decrease
      occurred in serum lysozyme at 29 days p.e. No specific antibodies against the
      parasite were detected in any sampling.

PMID- 16621607
TI  - Knowledge of one's kinematics improves perceptual discrimination.
AB  - We tested the hypothesis that our ability to detect fine kinematics variations is
      tuned to reveal more subtle differences when the motion pattern belongs to the
      observer compared to another individual. To this purpose, we analyzed the
      responses of 15 subjects in a same-different task on pairs of movements, which
      could belong to one or two different subjects. Self vs. Other comparisons were
      obtained by presenting both the observer's and another participant's kinematics.
      Subjects responded faster and more accurately when they observed their own
      gestures compared to movements of another participant. In the latter case, slight
      kinematic differences were more likely to remain undetected. These findings are
      discussed within an ecological framework: in observing others, we are more
      concerned with detection of goals and intentions, i.e., outstanding variations in
      motion patterns. Conversely, in self-observation detection of more subtle
      differences is required to facilitate learning and optimization of motor acts.

PMID- 16621606
TI  - Cloning and characterisation of mitochondrial manganese superoxide dismutase
      (mtMnSOD) from the giant freshwater prawn Macrobrachium rosenbergii.
AB  - A cDNA encoding a mitochondrial manganese superoxide dismutase (mtMnSOD) was
      cloned from the hepatopancreas of giant freshwater prawn Macrobrachium
      rosenbergii using reverse transcription polymerase chain reaction (RT-PCR) by
      degenerate primers. Both 3'- and 5'-regions were isolated by rapid amplification
      of cDNA end (RACE) PCR method. Analysis of nucleotide sequence revealed that the
      mtMnSOD full-length cDNA consists of 1202bp containing an open reading frame of
      654bp, which encodes a protein consisting of 218 amino acids including a signal
      peptide of 16 amino acid residues. The calculated molecular mass of the mature
      proteins (202 amino acids) is 24kDa with an estimated pI of 7.12. Two putative N
      glycosylation sites, NXT and NXS were observed in the mtMnSOD. Manganese
      superoxide dismutase signatures from 180 to 187 (DVWEHAYY), and four conserved
      amino acids responsible for binding manganese were observed (H48, H96, D180 and
      H184). Sequence comparison showed that the mtMnSOD deduced amino acid sequence of
      Macrobrachium rosenbergii has similarity of 88%, 78%, 56%, 54% and 46% to that of
      blue crab Callinectes sapidus, crucifix crab Charybdis feriatus, brown shrimp
      Farfantepenaeus aztecus, European lobster Palinurus vulgaris, and grass shrimp
      Palaemontes pugio, respectively, and has similarity of 45%, 44%, 43%, 26% and 25%
      to cytMnSOD (cytosolic MnSOD) deduced amino acid sequence of blue crab C.
      sapidus, prawn M. rosenbergii, tiger shrimp Penaeus monodon, grass shrimp P.
      pugio and brown shrimp F. aztecus, respectively. Quantitative real-time RT-PCR
      analysis showed that levels of mtMn-SOD transcripts in hepatopancreas and
      haemocytes were not significantly different between the M. rosenbergii injected
      with Lactococcus garvieae, and that injected with saline after 3h to 24h.

PMID- 16621608
TI  - Traumatic memories of war veterans: not so special after all.
AB  - Several authors have argued that traumatic experiences are processed and
      remembered in a qualitatively different way from neutral events. To investigate
      this issue, we interviewed 121 Croatian war veterans diagnosed with posttraumatic
      stress disorder (PTSD) about amnesia, intrusions (i.e., flashbacks and
      nightmares), and the sensory qualities of their most horrific war memories.
      Additionally, they completed a self-report scale measuring dissociative
      experiences. In contrast to what one would expect on the basis of theories
      emphasizing the special status of traumatic memories, amnesia, and high frequency
      intrusions were not particularly typical for our sample of traumatized
      individuals. Moreover, traumatic memories were not qualitatively different from
      neutral memories with respect to their stability and sensory qualities. The
      severity of PTSD symptoms was not significantly correlated with dissociative
      experiences. Our findings do not support the existence of special memory
      mechanisms that are unique to experiencing traumatic events.

PMID- 16621609
TI  - Range-wide phylogeography of a temperate lizard, the five-lined skink (Eumeces
      fasciatus).
AB  - We used mitochondrial DNA and microsatellite loci to examine the phylogeographic
      patterns of the most broadly distributed lizard in eastern North America, the
      five-lined skink (Eumeces fasciatus). We infer that longitudinal phylogeographic
      patterns in E. fasciatus are consistent with fragmentation due to refugial and
      post-glacial dynamics, but that deep divergences within the species imply
      historical fragmentation that predates the Pleistocene. The effect of multiple
      refugia is implied from our nested clade analyses, including a northern refugium
      in Wisconsin. Analysis of population structure using nuclear microsatellite data
      within the species suggests the importance of glacial dynamics in shaping more
      recent genetic structuring within one widely distributed lineage that ranges from
      the Mississippi River to the Atlantic Ocean in longitude and from southern
      Ontario to the Gulf of Mexico in latitude. Results shed light on the historical
      processes that have influenced current population structure of a temperate
      lizard, support the striking similarity of longitudinal phylogeographic structure
      across many herpetofaunal species in eastern North America, and illustrate the
      utility of employing multiple markers in phylogeographic studies.

PMID- 16621610
TI  - Low-copy nuclear DNA, phylogeny and the evolution of dichogamy in the betel nut
      palms and their relatives (Arecinae; Arecaceae).
AB  - For the betel nut palm genus Areca and the other seven genera in subtribe
      Arecinae (Areceae; Arecoideae; Arecaceae) we collected DNA sequences from two low
      copy nuclear genes, phosphoribulokinase (PRK) and the second largest subunit of
      RNA polymerase II (RPB2). The data were used to evaluate monophyly of the
      subtribe and its component genera, explore the radiation of the group across its
      range, and examine evolution of protandry and protogyny, which is particularly
      diverse in Arecinae. The subtribe and some genera are not monophyletic. Three
      lineages of Arecinae are recovered: one widespread, but centered on the Sunda
      Shelf, another endemic to the islands east of Wallace's line and a third,
      comprising the Sri Lanka endemic Loxococcus, that is most closely related to
      genera from outside subtribe Arecinae. Strong support is obtained for broadening
      the circumscription of the genus Hydriastele to include Gronophyllum, Gulubia and
      Siphokentia. In clarifying phylogenetic relationships, we have demonstrated that
      a perceived bimodal distribution of the subtribe across Wallace's line does not
      in fact exist. Character optimizations indicate that the evolution of protogyny,
      an unusual condition in palms, is potentially correlated with a large radiation
      in the genus Pinanga and possibly also to dramatic diversification in pollen
      morphology and genome size. The evolution of dichogamy in the clade endemic to
      the east of Wallace's line is complex and reveals a pattern of numerous
      transformations between protandry and protogyny that is in marked contrast with
      other Arecinae. We suggest that this contrast is most likely a reflection of
      differing geological histories and pollinator spectra in each region.

PMID- 16621611
TI  - Evolution of Afrotropical freshwater crab lineages obscured by morphological
      convergence.
AB  - We use sequence data derived from six DNA gene loci to examine evolutionary and
      biogeographic affinities among all freshwater crab families. With an emphasis on
      the Afrotropical fauna that includes Africa, Madagascar, and the Seychelles, we
      test the proposed Gondwanan cladogenesis of the group. Phylogenetic results
      demonstrate that contemporary distribution patterns of freshwater crab lineages
      are incongruent with the expected area cladogram of continental fragmentation.
      Instead, our phylogenetic estimate and divergence time estimation indicate a post
      Gondwanan, early Cretaceous cladogenesis for freshwater crabs implying that the
      acquisition of a freshwater lifestyle was achieved more recently. A dispersal
      hypothesis as opposed to vicariance appears to best explain the contemporary
      distribution pattern of this group. However, our results do not explicitly
      disprove a Gondwanan origin for the Afrotropical freshwater crabs. Alarmingly,
      these results suggest that most of the currently recognized freshwater crab
      families are unreliable taxonomic groupings since virtually no Afrotropical
      freshwater crab families formed monophyletic units thus obscuring inferred
      biogeographic relationships. Convergence in characters associated with the
      terminal segment of the mandibular palp is clearly a pervasive obstacle in the
      taxonomy of this group.

PMID- 16621612
TI  - Phylogeny, historical biogeography, and patterns of diversification for Pinus
      (Pinaceae): phylogenetic tests of fossil-based hypotheses.
AB  - Pines comprise one of the largest coniferous genera, are distributed throughout
      the Northern Hemisphere, and have an abundant fossil record. Distributions of
      fossils have been used to derive a three-step hypothesis of early pine evolution,
      which postulates a Mesozoic origin for the genus, east-west expansions across
      Laurasia, and retraction into Eocene refugia. Here, we present phylogenetic tests
      of this hypothesis using chloroplast sequence data from four loci for 83 pine
      species. We used the fossil-based hypothesis to derive null expectations
      concerning monophyly of taxonomic groups, dates of cladogenesis, and patterns of
      diversification. Phylogenetic analyses using several algorithms subsequently
      provided rigorous tests of these expectations. Our inferred phylogenies
      illustrated broad congruence with taxonomic groups, but highlighted consistent
      problems within subgenus Strobus. Estimated minimum dates of divergence derived
      from relaxed clock methods were largely consistent with the fossil record and
      yielded a date for the ingroup node of Pinus of 128+/-4 mya, depending upon the
      calibration used for subgenus Pinus. Ancestral area reconstructions showed Pinus
      to have most likely originated in Eurasia. Major clades differed in biogeographic
      patterns, but were consistent with the fossil-based hypothesis. We found weak
      support, however, for a change in diversification rate in the Eocene as
      interpretations of fossil distributions would have predicted.

PMID- 16621613
TI  - Intercontinental biogeography of subfamily Orontioideae (Symplocarpus,
      Lysichiton, and Orontium) of Araceae in Eastern Asia and North America.
AB  - Symplocarpus, Lysichiton, and Orontium (Orontioideae) are three of the few north
      temperate genera of the primarily tropical Araceae. Symplocarpus is disjunctly
      distributed in eastern Asia (3 spp.) and eastern North America (1 sp.);
      Lysichiton has an intercontinental discontinuous distribution in eastern Asia (1
      sp.) and northwestern North America (1 sp.); and the monotypic Orontium is
      restricted to eastern North America. Phylogenetic analysis of the trnL-F and ndhF
      sequences supports (1) the monophyly of both Symplocarpus and Lysichiton, (2) the
      sister-group relationship of Symplocarpus and Lysichiton, and (3) the clade of
      Orontium, Symplocarpus, and Lysichiton. Although Symplocarpus shows a much wider
      disjunction than Lysichiton, the estimated divergence time of the former [4.49+/
      1.69 or 6.88+/-4.18 million years ago (mya)] was similar to that of the latter
      (4.02+/-1.60 or 7.18+/-4.33 mya) based on the penalized likelihood and the
      Bayesian dating methods, respectively. Eastern Asia was suggested to be the
      ancestral area of the Symplocarpus-Lysichiton clade based on the dispersal
      vicariance analysis. Our biogeographic results support independent migrations of
      Symplocarpus and Lysichiton across the Bering land bridge in the late Tertiary
      (Pliocene/late Miocene). Fossil evidence suggests Orontioideae dated back to the
      late Cretaceous in the temperate Northern Hemisphere (72 mya). The relative rate
      test shows similar substitution rates of the trnL-F sequences between the proto
      and the true aroids, although the latter has substantially higher species
      diversity. The proto Araceae perhaps suffered from a higher rate of extinction in
      the temperate zone associated with periods of climatic cooling in the Tertiary.

PMID- 16621614
TI  - The complete mitochondrial genome of Flustrellidra hispida and the phylogenetic
      position of Bryozoa among the Metazoa.
AB  - The complete mitochondrial genome of Flustrellidra hispida (Bryozoa,
      Ctenostomata, Flustrellidridae) was sequenced using a transposon-mediated
      approach. All but one of the 36 genes were identified (trnS2). The genome is
      13,026 bp long, being one of the smallest metazoan mitochondrial genomes
      sequenced to date with a unique gene order when compared to other Metazoa. The
      genome has an overall AT richness of 59.4%. We found seven regions of overlaps
      between tRNAs and protein-coding genes ranging from 2 to 11 nt, and seven regions
      of overlap between tRNAs, ranging from 1 to 8 nt, resulting in a total number of
      46 overlapping nucleotides. Genes nad4, cox2, atp8, and nad3 are terminated by
      the abbreviated stop codon T and cytb is suggested to terminate on (ACT)AA; we
      postulate that mRNA editing is required to remove AC for TAA to be functional in
      terminating translation. Phylogenetic analysis of nucleotide and amino acid data
      place Flustrellidra in the Lophotrochozoa. DNA for this study originated from two
      populations resulting in a contig consisting of multiple haplotypes. Twenty-seven
      SNP sites were detected, the majority occurring in cox1 and nad5. With cox1
      already established as a marker in bryozoan studies, we advocate the further
      testing of nad5.

PMID- 16621615
TI  - Seed plant phylogeny: gnetophytes are derived conifers and a sister group to
      Pinaceae.
AB  - The phylogenetic position of gnetophytes has long been controversial. We
      sequenced parts of the genes coding for the largest subunit of nuclear RNA
      polymerase I, II, and III and combined these sequences with those of four
      chloroplast genes, two mitochondrial genes, and 18S rRNA genes to address this
      issue. Both maximum likelihood and maximum parsimony analyses of the sites not
      affected by high substitution levels strongly support a phylogeny where
      gymnosperms and angiosperms are monophyletic, where cycads are at the base of
      gymnosperm tree and are followed by ginkgos, and where gnetophytes are grouped
      within conifers as the sister group of pines. The evolution of several
      morphological and molecular characters of gnetophytes and conifers will therefore
      need to be reinterpreted.

PMID- 16621616
TI  - Phylogeny of venus clams (Bivalvia: Venerinae) as inferred from nuclear and
      mitochondrial gene sequences.
AB  - Venerinae (Heterodonta: Veneridae) is a diverse, commercially important, and
      cosmopolitan marine bivalve subfamily. Recent workers synonymized it with the
      subfamily Chioninae, due to their overall morphological similarity. The use of
      traditional shell-based characters alone, however, is questionable for resolving
      phylogenetic relationships of this group. A phylogenetic study was carried out,
      based on nucleotide sequences of the mitochondrial large ribosomal subunit (16S),
      cytochrome oxidase subunit I (COI), and the nuclear protein-coding gene histone
      3, to investigate the relationships and circumscription of Venerinae and the
      phylogenetic pattern of characters in this group. This study consists of a total
      of 55 taxa: 13 venerine genera, 24 chionine taxa, and 18 taxa of other venerid
      subfamilies. We analyzed the alignments using a Bayesian approach using Markov
      Chain Monte Carlo tree sampling and maximum parsimony methods. The resulting
      phylogenetic hypothesis suggests that Chioninae and Venerinae are actually
      discrete taxa, but that the circumscription suffered from misplacement of some
      genera. Our analysis showed that the former chionine genera Chamelea and
      Clausinella should be placed in Venerinae, as sister taxa to Venus. We re
      analyzed morphological and anatomical features in light of the molecular data to
      describe monophyletic entities. Features of the hinge and internal shell as well
      as the degree of siphonal fusion are identified as characters to morphologically
      distinguish the two subfamilies. Of the three genes used in this study, only COI
      (commonly used as "barcoding" gene) posed substantial problems in obtaining
      sequence data from older museum material.

PMID- 16621617
TI  - No effect of immunomodulatory therapy in focal epilepsy with positive glutamate
      receptor type 3--antibodies.
AB  - Antibodies against the glutamate receptor type 3-(GluR3) have been found in
      association with Rasmussen's encephalitis (RE) but were also detected in patients
      with non-inflammatory focal epilepsies. We report the case of an 18-year-old
      patient with treatment refractory left mesial temporal lobe epilepsy accompanied
      by high levels of GluR3 antibodies. Different from experiences in patients with
      RE immunomodulatory therapy by use of intravenous gammaglobulines neither altered
      GluR3 serum levels nor had any effect on seizure frequency in our patient.
      Interestingly, GluR3 serum levels remained positive after successful surgical
      intervention leading to patient's seizure freedom.

PMID- 16621618
TI  - Intravenous methyl prednisolone in patients with solitary cysticercus granuloma:
      a random evaluation.
AB  - PURPOSE: To evaluate the role of intravenous methyl prednisolone in patients with
      solitary cysticercus granuloma with new-onset seizures. METHODS: In this open
      label, randomized, prospective, follow-up study, 52 patients with new-onset
      seizures and a single enhancing CT lesion of cysticercus were randomly divided in
      two groups to receive either intravenous methyl prednisolone for 5 days along
      with antiepileptic drug (n=25) or antiepileptic drug monotherapy (n=27) alone.
      The patients were followed up for at least for 9 months. Repeat CT scans were
      performed after 2 months. RESULTS: After 2 months, lesion disappeared in 60%
      patients of intravenous methyl prednisolone group and 18.5% patients receiving
      only antiepileptic drug (p=0.001). As far as seizure recurrence was concerned, a
      lower number (16% versus 33%) of intravenous methyl prednisolone treated patient
      had recurrence, the difference was insignificant. CONCLUSION: Intravenous methyl
      prednisolone therapy helps in early resolution of solitary cysticercus granuloma.

PMID- 16621619
TI  - Preliminary study on diffraction enhanced radiographic imaging for a canine model
      of cartilage damage.
AB  - OBJECTIVE: To demonstrate the ability of a novel radiographic technique,
      Diffraction Enhanced Radiographic Imaging (DEI), to render high contrast images
      of canine knee joints for identification of cartilage lesions in situ. METHODS:
      DEI was carried out at the X-15A beamline at Brookhaven National Laboratory on
      intact canine knee joints with varying levels of cartilage damage. Two
      independent observers graded the DE images for lesions and these grades were
      correlated to the gross morphological grade. RESULTS: The correlation of gross
      visual grades with DEI grades for the 18 canine knee joints as determined by
      observer 1 (r2 = 0.8856, P = 0.001) and observer 2 (r2 = 0.8818, P = 0.001) was
      high. The overall weighted kappa value for inter-observer agreement was 0.93,
      thus considered high agreement. CONCLUSION: The present study is the first study
      for the efficacy of DEI for cartilage lesions in an animal joint, from very early
      signs through erosion down to subchondral bone, representing the spectrum of
      cartilage changes occurring in human osteoarthritis (OA). Here we show that DEI
      allows the visualization of cartilage lesions in intact canine knee joints with
      good accuracy. Hence, DEI may be applicable for following joint degeneration in
      animal models of OA.

PMID- 16621620
TI  - Mechanical properties of articular cartilage covered by the meniscus.
AB  - OBJECTIVE: To investigate the mechanical properties and morphological
      characteristics of articular cartilage on the tibial plateau of human knees,
      including the region covered by the meniscus. DESIGN: Using a 1-mm diameter flat
      ended cylindrical probe to apply a constant load (0.6 MPa) at specific sites on
      the tibial plateau, the mechanical properties of articular cartilage were studied
      using seven cadaver knees. Comparison was made between data obtained by the
      cartilage covered by the meniscus and that not covered. This was done for both
      the medial and lateral plateaus. Histological sections of the articular cartilage
      were also performed to study differences between cartilage from these regions of
      the tibial plateau. RESULTS: Compared to cartilage that was not covered by the
      meniscus, the articular cartilage beneath the meniscus showed a significantly
      (P<0.05) larger modulus by as much as 70%, and was less thick by about 40%. Also,
      the subchondral bone quantity and calcified layer thickness were observed to be
      significantly lesser in the regions covered by the meniscus. CONCLUSIONS: Our
      findings revealed a significant difference between the mechanical properties and
      associated structures of articular cartilage in the region covered by the
      meniscus compared with the articular cartilage not covered by the meniscus.

PMID- 16621621
TI  - Placement of intra-articular injection verified by the backflow technique.
AB  - OBJECTIVE: To develop and to assess a simple, inexpensive method for
      ascertaining, without any imaging procedure, the intra-articular placement of the
      needle in the knee for intra-articular injections. METHODS: Outpatients referred
      for intra-articular treatment with "dry" symptomatic knee osteoarthritis were
      included in this prospective study. "Dry" knee disease was defined as a knee
      without any clinically detectable effusion. Once intra-articular positioning of
      the needle considered adequate using the backflow technique, contrast solution
      was injected using the same needle without changing its position and immediately
      afterwards lateral and anterior-posterior X-rays were taken to assess the needle
      position. RESULTS: Of the 32 of 33 cases with obtained backflow, the needle was
      correctly placed in all cases. In the remaining case, the needle was extra
      articularly positioned. The concordance between the two techniques using the
      Cohen's Kappa was 1 [CI 95%: 0.22-1]. CONCLUSION: The backflow technique allows
      to accurate the intra-articular placement of the needle for "dry" knee joints
      injection. This technique can be proposed as a learning tool as well as a daily
      practice technique to ascertaining intra-articular knee injections without using
      fluoroscopy with injection of contrast material. Further studies are needed to
      assess the technique for other joint injections.

PMID- 16621622
TI  - STRO-1+ mesenchymal precursor cells located in synovial surface projections of
      patients with osteoarthritis.
AB  - OBJECTIVE: To investigate the presence of mesenchymal precursor cells (MPCs) in
      synovial surface projections of patients with osteoarthritis (OA), to
      characterize their phenotype and to show their localization. METHODS: Progenitor
      cells in synovial surface projections were identified by immunohistochemistry,
      morphometric analysis and confocal laser scanning microscopy using the following
      phenotypic markers: STRO-1, CD34, and alpha smooth muscle actin (alpha-SMA).
      RESULTS: In the synovial tissue of all 21 patients with OA MPCs were detected.
      Immunohistochemistry and subsequent morphometric analysis showed that
      approximately twice as many STRO-1+ cells/mm2 were observed in synovial tissue of
      patients with OA as compared to healthy organ donors and that number of STRO-1+
      cells/mm2 correlated with total cell number/mm2. Interestingly, in the synovial
      tissue of patients with OA, twice as many STRO-1+ cells/mm2 were found in
      synovial surface projections as compared to the sublining area without villi.
      Using confocal laser scanning microscopy two populations of STRO-1+ MPCs could be
      detected in synovial surface projections. Single STRO-1+ cells that co-expressed
      alpha-SMA resemble a population of pericyte precursors required to stabilize the
      immature vasculature. The second STRO-1+ cell population that was found lacked
      alpha-SMA but co-expressed CD34 on their surface with low intensity. CONCLUSION:
      Here we can show that in the synovial tissue of patients with OA twice as many
      STRO-1+ MPCs can be found in synovial surface projections as compared to the
      sublining area. These cells are preferentially located at the basis and in the
      protruding end of the synovial surface projection.

PMID- 16621623
TI  - CMV promotor activity during ES cell differentiation: potential insight into
      embryonic stem cell differentiation.
AB  - The activity of the P(CMV IE) promoter was studied during the differentiation of
      ES cells into neurons. In order to do this, stable embryonic stem (ES) cell lines
      that express enhanced green fluorescent protein (EGFP) under the control of P(CMV
      IE) were created and these ES cells were differentiated by aggregation of cells
      in the presence of retinoic acid (RA). Based on our observations that the
      activity of P(CMV IE) was highest in undifferentiated cells, and that cell-cell
      interaction and addition of RA that lead to enhanced cell proliferation also
      increased expression from P(CMV IE), we hypothesized that the activity of P(CMV
      IE) was positively regulated in cycling cells. However, when analysis was done at
      the single cell level it was found that BrdU label and EGFP expression were not
      correlated. EGFP expression was found to be down-regulated in many cells that
      were BrdU positive and conversely there were significant numbers of BrdU negative
      cells that were EGFP positive. Further, P(CMV IE) activity was not observed in
      cells that were nestin positive or in differentiated neurons, but P(CMV IE) was
      active in cells with a fibroblast-like morphology. Finally, several proteins
      present in undifferentiated ES cells were found to bind to regulatory regions of
      P(CMV IE). These were absent when cells were aggregated in the presence of RA.
      The above results have implications for expression of transgenes in ES cells as
      well as providing new insight into the mechanism of lineage restriction.

PMID- 16621624
TI  - In vitro expansion of long-term repopulating hematopoietic stem cells in the
      presence of immobilized Jagged-1 and early acting cytokines.
AB  - There is an increasing body of evidence that suggests that genes involved in cell
      fate decisions and pattern formation during development also play a key role in
      the continuous cell fate decisions made by adult tissue stem cells. Here we show
      that prolonged in vitro culture (14 days) of murine bone marrow lineage negative
      cells in medium supplemented with three early acting cytokines (stem cell factor,
      Flk-2/Flt-3 ligand, thrombopoietin) and with immobilized Notch ligand, Jagged-1,
      resulted in robust expansion of serially transplantable hematopoietic stem cells
      with long-term repopulating ability. We found that the absolute number of marrow
      cells was increased approximately 8 to 14-fold in all cultures containing
      recombinant growth factors. However, the frequency of high quality stem cells was
      markedly reduced at the same time, except in cultures containing growth factors
      and Jagged-1-coated Sepharose-4B beads. The absolute number of hematopoietic
      cells with long-term repopulating ability was increased approximately 10 to 20
      fold in the presence of multivalent Notch ligand. These results support a role
      for combinatorial effects by Notch and cytokine-induced signaling pathways in
      regulating hematopoietic stem cell fate and to a potential role for Notch ligand
      in increasing cell numbers in clinical stem cell transplantation.

PMID- 16621625
TI  - Mitochondrial targeting of human protoporphyrinogen oxidase.
AB  - Variegate porphyria is an autosomal dominant disorder of heme metabolism
      resulting from a deficiency in protoporphyrinogen oxidase, an enzyme located on
      the inner mitochondrial membrane. This study examined the effect of three South
      African VP-causing mutations (H20P, R59W, R168C) on mitochondrial targeting. Only
      H20P did not target, and of eight protoporphyrinogen oxidase-GFP chimeric fusion
      proteins created, N-terminal residues 1-17 were found to be the minimal
      protoporphyrinogen oxidase sequence required for efficient mitochondrial
      targeting. Removal of this N-terminal sequence displayed mitochondrial
      localization, suggesting internal mitochondrial targeting signals. In addition,
      six constructs were engineered to assess the effect of charge and helicity on
      mitochondrial targeting of the protein. Of those engineered, only the PPOX20/H20P
      GFP construct abolished mitochondrial targeting, presumably through disruption of
      the protoporphyrinogen oxidase alpha-helix. Based on our results we propose a
      mechanism for protoporphyrinogen oxidase targeting to the mitochondrion.

PMID- 16621626
TI  - Non-receptor activators of heterotrimeric G-protein signaling (AGS proteins).
AB  - G-protein coupled receptor (GPCR) signaling represents one of the most conserved
      and ubiquitous means in mammalian cells for transferring information across the
      plasma membrane to the intracellular environment. Heterotrimeric G-protein
      subunits play key roles in transducing these signals, and intracellular
      regulators influencing the activation state and interaction of these subunits
      regulate the extent and duration of GPCR signaling. One class of intracellular
      regulator, the non-receptor activators of G-protein signaling (or AGS proteins),
      are the major focus of this review. AGS proteins provide a basis for
      understanding the function of heterotrimeric G-proteins in both GPCR-driven and
      GPCR independent cellular signaling pathways.

PMID- 16621627
TI  - Microtubule dynamics and organization during hyphal growth and branching in
      Neurospora crassa.
AB  - By confocal microscopy, we analyzed microtubule (Mt) behavior during hyphal
      growth and branching in a Neurospora crassa strain whose Mts had been tagged with
      GFP. Images were assembled spatially and temporally to better understand the 3-D
      organization of the microtubular cytoskeleton and a clearer view of its dynamics.
      Cytoplasmic Mts were mainly arranged longitudinally along the hyphal tube.
      Straight segments were rare; most Mts showed a distinct helical curvature with a
      long pitch and a tendency to intertwine with one another to form a loosely
      braided network throughout the cytoplasm. This study revealed that the
      microtubular cytoskeleton of a hypha advances as a unit, i.e., as the cell
      elongates, it moves forward by bulk flow. Nuclei appeared trapped in the
      microtubular network and were carried forward in unison as the hypha elongated.
      During branching, one or more cortical Mts became associated with the incipient
      branch and were pulled into the emergence of the branch. As extension of the
      branch and distortion of the Mts continued, Mts soon were severed with both new
      Mt ends (+ and -) present in the new branch. Although the exact mechanisms for
      addition Mt recruitment into the branch remains an open question, the recorded
      evidence indicates both bulk insertion of established cortical parent-hypha Mts
      as well as in situ polymerization were involved. The latter conclusion was
      supported by FRAP studies showing evidence of Mt nucleation and polymerization
      assembly in the growing tip of the developing branch. Nuclei entered the branch
      entrapped in the advancing network of Mts.

PMID- 16621628
TI  - Genetics of self/nonself recognition in Serpula lacrymans.
AB  - This study provides an analysis of the vegetative incompatibility system in
      Serpula lacrymans (Basidiomycota), a genetic system used to recognize nonself in
      fungi. Seventy-five worldwide isolates could be grouped into eight vegetative
      compatibility (VC) types, some of them distributed on different continents.
      Mating studies combined with vegetative incompatibility analyses revealed that
      the vegetative incompatibility response between isolates mainly could be
      explained by two biallelic vegetative incompatibility (vic) loci. The frequency
      distributions of the interpreted vic alleles do not seem to support the idea of
      frequency-dependent or balancing selection acting on the vic loci. We find little
      genetic variation at the vic loci and in one of the loci there was a significant
      heterozyote deficiency among strains in the overall material. The results may be
      explained by a recent worldwide dispersal of a few S. lacrymans isolates and,
      correspondingly, only a few vic alleles are being maintained in these
      populations.

PMID- 16621629
TI  - Nitric oxide inhibits neutrophil migration by a mechanism dependent on ICAM-1:
      role of soluble guanylate cyclase.
AB  - In the present study, we addressed the role of intercellular adhesion molecule
      type 1 (ICAM-1/CD54) in neutrophil migration to inflammatory site and whether the
      inhibitory effect of nitric oxide (NO) upon the neutrophil rolling, adhesion and
      migration involves down-modulation of ICAM-1 expression through a cyclic GMP
      (cGMP) dependent mechanism. It was observed that neutrophil migration induced by
      intraperitoneal administration of endotoxin (LPS), carrageenan (Cg) or N-formyl
      peptide (fMLP) in ICAM-1 deficient (ICAM-1-/-) is similar to that observed in
      wild type (WT) mice. The treatment of mice with NO synthase (NOS) inhibitors, NG
      nitro-l-arginine, aminoguanidine or with a soluble guanylate cyclase (sGC)
      inhibitor, ODQ enhanced LPS- or Cg-induced neutrophil migration, rolling and
      adhesion on venular endothelium. These parameters induced by LPS were also
      enhanced by 1400 W, a specific iNOS inhibitor, treatment. On the other hand, the
      treatment of the mice with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor,
      reduced these parameters induced by LPS or Cg by a mechanism sensitive to ODQ
      pretreatment. The NOS inhibitors did not enhance LPS-, Cg- or fMLP-induced
      migration and adhesion in ICAM-1-/- mice. Moreover, genetic (iNOS-/- mice) or
      pharmacological inhibition of NOS or of sGC enhanced LPS-induced ICAM-1
      expression on mesenteric microcirculation vessels of WT mice. By contrast, SNAP
      reduced the ICAM-1 expression by a mechanism dependent on cGMP. In conclusion,
      the results suggest that although during inflammation, ICAM-1 does not contribute
      to neutrophil migration, it is necessary for the down-modulatory effect of
      inflammation-released NO on the adhesion and transmigration of neutrophils.
      Moreover, these NO effects are mediated via cGMP.

PMID- 16621630
TI  - Burkitt leukemia with numb chin syndrome and cavernous sinus involvement.
AB  - Cavernous sinus syndrome is a rare event. Non-Hodgkin lymphomas, are one possible
      cause. Neurological presentation of these lymphomas is also exceptional. We
      report the case of an 11-year-old boy that developed a right third cranial nerve
      palsy and numbness in the distribution of the right mental nerve, with normal
      CSF, and enlargement of cavernous sinus on the same side, who was diagnosed
      Burkitt leukemia.

PMID- 16621631
TI  - Rapid MRI method for mapping the longitudinal relaxation time.
AB  - A novel method for mapping the longitudinal relaxation time in a clinically
      acceptable time is developed based on a recent proposal [J.-J. Hsu, I.J. Lowe,
      Spin-lattice relaxation and a fast T1-map acquisition method in MRI with
      transient-state magnetization, J. Magn. Reson. 169 (2004) 270-278] and the speed
      of the spiral pulse sequence. The method acquires multiple curve-fitting samples
      with one RF pulse train. It does not require RF pulses of specific flip angles
      (e.g., 90 degrees or 180 degrees ), nor are the long recovery waiting time and
      the measurement of the magnetization at thermal equilibrium needed. Given the
      value of the flip angle, the curve fitting is semi-logarithmic and not
      computationally intensive. On a heterogeneous phantom, the average percentage
      difference between measurements of the present method and those of an inversion
      recovery method is below 2.7%. In mapping the human brain, the present method,
      for example, can obtain four curve-fitting samples for five 128 x 128 slices in
      less than 3.2s and the results are in agreement with other studies in the
      literature.

PMID- 16621632
TI  - Accurate measurement of long-range heteronuclear coupling constants from
      undistorted multiplets of an enhanced CPMG-HSQMBC experiment.
AB  - Here, we present a modified CPMG-HSQMBC experiment which is capable to reduce the
      detrimental phase twists in the "long-range" connectivity multiplets caused by
      proton-proton couplings. We demonstrate that concerted CPMG pulse trains applied
      on both nuclei in the starting CPMG-INEPT transfer step can considerably be
      improved by composite pi pulses that compensate for pulse imperfections and off
      resonance effects. Experimental optimization of the interpulse delay within the
      CPMG cycle was found to be crucial in order to achieve the best possible
      "decoupling" of homonuclear coupling modulation.

PMID- 16621633
TI  - High-resolution four-dimensional carbon-correlated 1H-1H ROESY experiments
      employing isotags and the filter diagonalization method for effective assignment
      of glycosidic linkages in oligosaccharides.
AB  - Four-dimensional nuclear magnetic resonance spectroscopy of oligosaccharides that
      correlates 1H-1H ROESY cross peaks to two additional 13C frequency dimensions is
      reported. The 13C frequencies were introduced by derivatization of all free
      hydroxyl groups with doubly 13C-labeled acetyl isotags. Pulse sequences were
      optimized for processing with the filter diagonalization method. The extensive
      overlap typically observed in 2D ROESY 1H-1H planes was alleviated by resolution
      of ROESY cross peaks in the two added dimensions associated with the carbon
      frequencies of the isotags. This enabled the interresidue 1H-1H ROESY cross peaks
      to be unambiguously assigned hence spatially proximate sugar spin systems across
      glycosidic bonds could be effectively ascertained. An experiment that selectively
      amplifies interresidue ROESY 1H-1H cross peaks is also reported. It moves the
      magnetization of an intraresidue proton normally correlated to a sugar H-1 signal
      orthogonally along the z axis prior to a Tr-ROESY mixing sequence. This virtually
      eliminates the incoherent intraresidue ROESY transfer, suppresses coherent TOCSY
      transfer, and markedly enhances the intensity of interresidue ROESY cross peaks.

PMID- 16621634
TI  - A theory of mode of action of azolylalkylquinolines as DNA binding agents using
      automated flexible ligand docking.
AB  - Azolylalkylquinolines (AAQs) are a family of quinolines with varying degrees of
      cytotoxic activity (comparable or moderately superior to adriamycin in some
      cases) developed in the past decade in our group where their exact mode of action
      is still unclear. In this study the most probable DNA binding mode of AAQs was
      investigated employing a novel flexible ligand docking approach by using AutoDock
      3.0. Forty-nine AAQs with known experimental inhibitory activity were docked onto
      d(CGCAAATTTGCG)(2), d(CGATCG)(2) and d(CGCG)(2) oligonucleotides retrieved from
      the Protein Data Bank (PDB IDs: 102D, 1D12 and 1D32, respectively) as the
      representatives of the three plausible models of interactions between
      chemotherapeutic agents and DNA (groove binding, groove binding plus
      intercalation and bisintercalation, respectively). Good correlation (r(2)=0.64)
      between calculated binding energies and experimental inhibitory activities was
      obtained using groove binding plus intercalation model for phenyl
      azolylalkylquinoline (PAAQ) series. Our findings show that the most probable mode
      of action of PAAQs as DNA binding agents is via intercalation of quinolinic
      moiety between CG base pairs with linker chain and azole moiety binding to the
      minor groove.

PMID- 16621635
TI  - CBS-QB3 calculation of quantum chemical molecular descriptors of isomeric
      thiadiazoles.
AB  - The results of the calculation of several molecular descriptors of isomeric
      thiadiazoles through the CBS-QB3 model chemistry are presented in this work. The
      results could be useful in quantitative structure-activity relationship (QSAR) or
      quantitative structure-property relationship (QSPR) studies of derivatives of the
      nitrogen-containing analogs of thiophene.

PMID- 16621636
TI  - Efficient molecular surface generation using level-set methods.
AB  - Molecules interact through their surface residues. Calculation of the molecular
      surface of a protein structure is thus an important step for a detailed
      functional analysis. One of the main considerations in comparing existing methods
      for molecular surface computations is their speed. Most of the methods that
      produce satisfying results for small molecules fail to do so for large complexes.
      In this article, we present a level-set-based approach to compute and visualize a
      molecular surface at a desired resolution. The emerging level-set methods have
      been used for computing evolving boundaries in several application areas from
      fluid mechanics to computer vision. Our method provides a uniform framework for
      computing solvent-accessible, solvent-excluded surfaces and interior cavities.
      The computation is carried out very efficiently even for very large molecular
      complexes with tens of thousands of atoms. We compared our method to some of the
      most widely used molecular visualization tools (Swiss-PDBViewer, PyMol, and
      Chimera) and our results show that we can calculate and display a molecular
      surface 1.5-3.14 times faster on average than all three of the compared programs.
      Furthermore, we demonstrate that our method is able to detect all of the interior
      inaccessible cavities that can accommodate one or more water molecules.

PMID- 16621637
TI  - Homocysteine-induced changes in vascular reactivity of guinea-pig pulmonary
      arteries: role of the oxidative stress and poly (ADP-ribose) polymerase
      activation.
AB  - This study was aimed to examine the effects of homocysteine (Hcy) on vascular
      responsiveness of guinea-pig isolated pulmonary arteries and to investigate
      possible underlying mechanisms. In order to evaluate vascular reactivity,
      isometric tension studies were performed in response to potassium chloride (KCl),
      phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP).
      Incubation of pulmonary artery rings with Hcy (10(-3)M, 180min) resulted in
      significant inhibition of response to ACh (an endothelium-dependent
      vasodilator)(E(max): 55.3+/-6.7 vs. 13.1+/-2.0(*), P<0.05) while SNP (an
      endothelium-independent vasodilator)-induced relaxation was not changed
      significantly. Furthermore, Hcy enhanced KCl- and Phe-induced contraction of
      pulmonary artery rings (E(max): 1568+/-81 vs. 2101+/-145(*)mg for KCl and 1081+/
      101 vs. 1544+/-117(*)mg for Phe, P<0.05). Pulmonary artery ring contractions
      induced by stepwise addition to Ca(2+) to high KCl solution with no Ca(2+) were
      also significantly augmented by Hcy incubation (E(max): 1750+/-121 vs. 2295+/
      134(*)mg, P<0.05). To investigate mechanisms of Hcy action, additional sets of
      experiments involving rings incubation with Hcy alone or with addition of Tiron
      (an intracellular superoxide anion scavenger, 10(-2)M), PJ34 (an inhibitor of
      polyADP-ribose polymerase, 3x10(-6)M), and combination of two antioxidant enzymes
      superoxide dismutase (SOD, 100U/ml) and catalase (CAT, 120U/ml) for 180min. The
      findings of our study clearly show that all these co-treatments significantly
      prevented the development of endothelial dysfunction induced by Hcy. Furthermore,
      the effect of Hcy on KCl- and Phe-induced contraction was significantly inhibited
      by the concomitant incubation with either SOD plus CAT, Tiron or PJ34. This study
      demonstrates that Hcy causes a significant alteration in vascular reactivity of
      pulmonary arteries, and this alteration seems to be via oxidative stress in
      pulmonary artery endothelium with subsequent DNA damage and activation of
      poly(ADP-ribose) polymerase (PARP) pathway.

PMID- 16621638
TI  - Tiotropium for the treatment of stable chronic obstructive pulmonary disease: a
      systematic review with meta-analysis.
AB  - BACKGROUND: Current guidelines recommend the use of inhaled tiotropium in
      patients with stable chronic obstructive pulmonary disease (COPD). However, this
      statement is based on a relatively small number of randomized controlled trials
      (RCTs) and related systematic reviews. This review was undertaken to incorporate
      the more recent evidence available about the effectiveness of tiotropium bromide
      compared with placebo, iptratropium bromide or long-acting beta-agonists (LABAs),
      for the treatment of stable COPD patients. DATA SOURCE: Medline, EMBASE, CINAHL,
      and the Cochrane Controlled Trials Register (to February 2006) were searched to
      identify all published RCTs. We also searched bibliographies of relevant
      articles. RESULTS: Data from 13 RCT (6078 subjects, 80% male) showed that
      tiotropium reduced COPD-related exacerbations (OR=0.76; 95% CI: 0.68-0.87) and
      hospital admissions (OR=0.59; 95% CI: 0.47-0.73) compared with placebo. Also,
      tiotropium showed statistically significant improvement in lung function,
      including trough, average, and peak FEV(1) and FVC from baseline, compared with
      placebo and ipratropium. The administration of inhaled tiotropium lead to 30%
      reduction in COPD-related admissions (OR= 0.67; 95% CI: 0.46-0.98) compared with
      LABAs. Finally, increases in FEV(1) and FVC from baseline were significantly
      larger with tiotropium than with LABAs. CONCLUSIONS: This review clearly supports
      the beneficial effects of the use of tiotropium in stable moderate-to-severe COPD
      patients, and increases the evidence in favor of the superiority of tiotropium on
      LABAs.

PMID- 16621639
TI  - Metabolic pathway analysis for rational design of L-methionine production by
      Escherichia coli and Corynebacterium glutamicum.
AB  - Metabolic pathway analysis was carried out to predict the metabolic potential of
      Corynebacterium glutamicum and Escherichia coli for the production of L
      methionine. Based on detailed stoichiometric models for these organisms, this
      allowed the calculation of the theoretically optimal methionine yield and related
      metabolic fluxes for various scenarios involving different mutants and process
      conditions. The theoretical optimal methionine yield on the substrates glucose,
      sulfate and ammonia for the wildtype of C. glutamicum is 0.49 (C-mol) (C-mol)(
      1), whereas the E. coli wildtype exhibits an even higher potential of 0.52 (C
      mol) (C-mol)(-1). Both strains showed completely different optimal flux
      distributions. C. glutamicum has a high flux through the pentose phosphate
      pathway (PPP), whereas the TCA cycle flux is very low. Additionally, it recruits
      a metabolic cycle, which involves 2-oxoglutarate and glutamate. In contrast, E.
      coli does minimize the flux through the PPP, and the flux through the TCA cycle
      is high. The improved potential of the E. coli wildtype is due to its membrane
      bound transhydrogenase and its glycine cleavage system as shown by additional
      simulations with theoretical mutants. A key point for maximizing methionine yield
      is the choice of the sulfur source. Replacing sulfate by thiosulfate or sulfide
      increased the maximal theoretical yield in C. glutamicum up to 0.68 (C-mol) (C
      mol)(-1). A further increase is possible by the application of additional C1
      sources. The highest theoretical potential was obtained for C. glutamicum
      applying methanethiol as combined source for C1 carbon and sulfur (0.91 (C-mol)
      (C-mol)(-1)). Substrate requirement for maintenance purposes reduces theoretical
      methionine yields. In the case of sulfide used as sulfur source a maintenance
      requirement of 9.2 mmol ATP g(-1) h(-1), as was observed under stress conditions,
      would reduce the maximum theoretical yield from 67.8% to 47% at a methionine
      production rate of 0.65 mmol g(-1) h(-1). The enormous capability of both
      organisms encourages the development of biotechnological methionine production,
      whereby the use of metabolic pathway analysis, as shown, provides valuable advice
      for future strategies in strain and process improvement.

PMID- 16621640
TI  - Understanding carotenoid metabolism as a necessity for genetic engineering of
      crop plants.
AB  - As a proof of concept, the qualitative and quantitative engineering of carotenoid
      formation has been achieved in crop plants. Successful reports in tomato, potato,
      rice, and canola all describe the enhancement of carotenoid with nutritional
      value, while in model systems such as tobacco and Arabidopsis the engineering of
      carotenoid to confer abiotic stress has been described. For all the successful
      applications there have been many examples of unintended/unpredicted phenotypes
      and results. Typically this has resided from our lack of understanding of
      carotenoid formation and its regulation. In the present article, we will review
      advances in carotenoid formation and its regulation to illustrate how metabolic
      engineering experiments have shed light on regulatory mechanisms.

PMID- 16621641
TI  - Metabolic engineering of malolactic wine yeast.
AB  - Malolactic fermentation is essential for the deacidification of high acid grape
      must. We have constructed a genetically stable industrial strain of Saccharomyces
      cerevisiae by integrating a linear cassette containing the Schizosaccharomyces
      pombe malate permease gene (mae1) and the Oenococcus oeni malolactic gene (mleA)
      under control of the S. cerevisiae PGK1 promoter and terminator sequences into
      the URA3 locus of an industrial wine yeast. The malolactic yeast strain, ML01,
      fully decarboxylated 5.5 g/l of malate in Chardonnay grape must during the
      alcoholic fermentation. Analysis of the phenotype, genotype, transcriptome, and
      proteome revealed that the ML01 yeast is substantially equivalent to the parental
      industrial wine yeast. The ML01 yeast enjoys 'Generally Regarded As Safe' status
      from the FDA and is the first genetically enhanced yeast that has been
      commercialized. Its application will prevent the formation of noxious biogenic
      amines produced by lactic acid bacteria in wine.

PMID- 16621642
TI  - Untreated classical galactosemia patient with mild phenotype.
AB  - Despite life-long galactose restriction, long-term complications generally occur
      in classical galactosemia. We report an adult male with classical galactosemia
      (Q188R homozygosity, severely reduced erythrocyte galactose-1-phosphate
      uridyltransferase activity) who has a surprisingly mild phenotype despite
      genotype and enzyme activity associated with severe phenotype. Moreover he has a
      normal galactose intake from the age of 3 years. This case is probably an example
      of the important role of yet unknown susceptibility and or modifier genes.

PMID- 16621643
TI  - In vitro characterization and in vivo expression of human very-long chain acyl
      CoA dehydrogenase.
AB  - Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a disorder of fatty
      acid beta-oxidation that can present at any age with cardiomyopathy,
      rhabdomyolysis, hepatic dysfunction, and/or nonketotic hypoglycemia. Through the
      expansion of newborn screening programs an increasing number of individuals with
      VLCAD deficiency are being identified prior to the onset of symptoms allowing
      early initiation of therapy. The development of a safe, durable, and effective
      VLCAD gene delivery system for use at the time of diagnosis could result in a
      significant improvement in the quality and duration of life for patients with
      VLCAD deficiency. To this end, we developed a construct containing the human
      VLCAD cDNA under the control of the strong CMV promoter (pCMV-hVLCAD). A novel
      rabbit polyclonal anti-VLCAD antibody was prepared using a 24 amino-acid peptide
      unique to the human VLCAD protein to study human VLCAD expression in immune
      competent mice. Antibody specificity was demonstrated in Western blots of human
      VLCAD deficient fibroblasts and in pCMV-hVLCAD transiently transfected VLCAD
      deficient fibroblasts. Transfected fibroblasts showed correction of the metabolic
      block as demonstrated by normalization of C14- and C16-acylcarnitine species in
      cell culture media and restoration of VLCAD activity in cells. Following tail
      vein injection of pCMV-hVLCAD into mice, we demonstrated expression of hVLCAD in
      liver. Altogether, these steps are important in the development of a durable gene
      therapy for VLCAD deficiency.

PMID- 16621644
TI  - High incidence of hyperoxaluria in generalized peroxisomal disorders.
AB  - The Zellweger spectrum disorders (ZSDs) are characterized by a generalized loss
      of peroxisomal functions caused by deficient peroxisomal assembly. Clinical
      presentation and survival are heterogeneous. Although most peroxisomal enzymes
      are unstable in the cytosol of peroxisome-deficient cells of ZSD patients, a few
      enzymes remain stable among which alanine:glyoxylate aminotransferase (AGT). Its
      deficiency causes primary hyperoxaluria type 1 (PH1, MIM 259900), an inborn error
      of glyoxylate metabolism characterized by hyperoxaluria, nephrocalcinosis, and
      renal insufficiency. Despite the normal level of AGT activity in ZSD patients,
      hyperoxaluria has been reported in several ZSD patients. We observed the
      unexpected occurrence of renal stones in a cohort of ZSD patients. This led us to
      perform a study in this cohort to determine the prevalence of hyperoxaluria in
      ZSDs and to find clinically relevant clues that correlate with the urinary
      oxalate load. We reviewed medical charts of 31 Dutch ZSD patients with prolonged
      survival (>1 year). Urinary oxalate excretion was assessed in 23 and glycolate in
      22 patients. Hyperoxaluria was present in 19 (83%), and hyperglycolic aciduria in
      14 (64%). Pyridoxine treatment in six patients did not reduce the oxalate
      excretion as in some PH1 patients. Renal involvement with urolithiasis and
      nephrocalcinosis was present in five of which one developed end-stage renal
      disease. The presence of hyperoxaluria, potentially leading to severe renal
      involvement, was statistically significant correlated with the severity of
      neurological dysfunction. ZSD patients should be screened by urinalysis for
      hyperoxaluria and renal ultrasound for nephrocalcinosis in order to take timely
      measures to prevent renal insufficiency.

PMID- 16621645
TI  - The MTHFR 1298CC and 677TT genotypes have opposite associations with red cell
      folate levels.
AB  - Individuals homozygous for the thermolabile variant (677TT) of
      methylenetetrahydrofolate reductase exhibit reduced folate status as evidenced by
      a drop in the biomarker red cell folate (RCF) compared to those who carry at
      least one 677C allele. We now report that a different polymorphism in the same
      enzyme, namely 1298A>C, is associated with increased RCF levels. Thus, these two
      common polymorphisms change a metabolic phenotype in opposite directions
      suggesting that their cancer protective associations are by different mechanisms.

PMID- 16621646
TI  - Structural and phylogenetic approaches to assess the significance of human
      Apolipoprotein E variation.
AB  - Apolipoprotein E (APOE) is an important gene whose common polymorphism, and
      precisely the e *4 allele, has been reportedly associated with some disorders,
      including Alzheimer's disease (AD) and coronary artery disease. In the course of
      previous surveys on AD patients and healthy individuals some rare variants were
      detected by means of Isoelectric focusing and denaturing high-performance liquid
      chromatography techniques. After a mutation in a gene is identified, the problem
      arises to understand its effective significance. Structure modelling and
      phylogenetic analysis methods are widely used to establish the possible
      deleterious effect of mutations. In this study their usefulness in the analysis
      of APOE variants was evaluated. The two combined methods provided helpful
      indications for distinguishing between mutations possibly involved in AD
      susceptibility and not deleterious mutations.

PMID- 16621647
TI  - A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile
      Dachshund with neuronal ceroid lipofuscinosis.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage
      diseases characterized by progressive neuropathy and the accumulation of
      autofluorescent cytoplasmic granules. Clinical signs of a new canine NCL began in
      a 9-month-old male Dachshund with vomiting, mental dullness, and loss of
      previously learned commands and rapidly progressed to include disorientation,
      ataxia, visual deficits, generalized myoclonic seizures, and death at 12 months
      of age. Neurons throughout the CNS contained autofluorescent storage granules
      that stained with periodic acid-Schiff and Luxol fast blue stains. Electron
      microscopy revealed that the storage granule contents consisted of curvilinear
      appearing material characteristic of human late infantile NCL caused by CLN2
      mutations. Nucleotide sequence analysis of canine TPP1, the ortholog of human
      CLN2, revealed a single nucleotide deletion in exon 4 which predicted a frame
      shift with a premature stop codon. Brain tissue from the affected dog lacked
      detectable activity of the tripeptidyl-peptidase enzyme encoded by TPP1, whereas
      the specific activities of 15 other lysosomal enzymes were higher than those in
      the brains of three control dogs. The affected Dachshund was homozygous for the
      mutant c.325delC allele, his sire and dam were heterozygotes, and 181 unrelated
      dogs, including 77 Dachshunds, were all homozygous for the wild-type allele. A
      DNA assay that detects the mutant allele will help Dachshund breeders avoid
      producing affected puppies in future generations. Furthermore, this Dachshund NCL
      may prove to be a useful model for studying the pathogenesis of neurodegeneration
      in human late infantile NCL and for evaluating novel therapeutic interventions
      for this disease.

PMID- 16621649
TI  - Role of interferons in the control of Lassa virus replication in human dendritic
      cells and macrophages.
AB  - Lassa fever is a hemorrhagic fever caused by Lassa virus (LV), which primarily
      targets human dendritic cells (DC) and macrophages (MP). Massive numbers of viral
      particles are released with no effect on the viability, activation or maturation
      of these cells. LV does not inhibit the activation of cells induced by sCD40L or
      LPS. We report here the consequences of exogenous activation of LV-infected human
      DC and MP for viral replication. The activation of cells with lipopolysaccharide
      or exogenous poly(I-C) and the transfection of cells with poly(I-C) strongly
      inhibited LV replication, at least partly by inducing type I interferon (IFN)
      synthesis. In contrast, cell stimulation with sCD40L did not induce type I IFN
      responses or inhibit LV release. Recombinant type I IFNs strongly inhibited LV
      replication in both cell types, whereas IFNgamma and IFNlambda did not. The
      modest type I IFN production observed in LV-infected MP, but not in DC, was
      involved in controlling LV replication in MP. These results provide an
      explanation for the slower replication of LV in MP than in DC, and suggest that
      type I IFNs are crucial in the control of LV.

PMID- 16621650
TI  - Age estimation from the degree of osteophyte formation of vertebral columns in
      Japanese.
AB  - To assess the age estimation from the degree of osteophyte formation of vertebral
      column, we set grading scores from 0 to 3 for the osteophyte formation based on
      the height of the process of vertebral column, and defined the average of the
      values at the cervical, thoracic and lumbar parts of the vertebra to be
      'osteophyte formation index' for an individual. We evaluated osteophyte formation
      in autopsied 225 bodies (138 males, 87 females) during 5 years, and statistically
      analyzed the integrated data. The following were statistically obtained for each
      sex: correlation coefficient, regression equation, standard error of estimate
      (SE) between the score at each part of the vertebral column and age, and between
      'osteophyte formation index' and age. In all the parts of the vertebra, there was
      a significant correlation between the score value and age. We recognized a
      significant correlation between 'osteophyte formation index' (X) and age (Y), and
      regression lines were Y = 37.90 + 12.07X (SE; 12.6 y.o.) in males and Y =
      36.67+18.64X (SE; 11.9 y.o.) in females. It was apparent that to know the degree
      of the osteophyte formation was useful in age estimation.

PMID- 16621651
TI  - Correlation between glial fibrillary acidic protein-positive astrocytes and age
      in the human hippocampus.
AB  - The hippocampus is one of the areas most vulnerable to histopathological changes,
      and such changes may yield useful information in forensic medicine. We found that
      glial fibrillary acidic protein (GFAP)-positive astrocytes are frequently found
      in the hippocampus of consecutive series of forensic brains, distributed
      predominantly in the hippocampal CA4 and hippocampal sulcus (HS) regions. The
      present study counted GFAP-positive astrocytes in these regions and investigated
      associations with age, cause of death and postmortem time. Significant
      correlations were found between age and number of GFAP-positive astrocytes in
      both CA4 and HS regions. Number of GFAP-positive astrocytes increases in an age
      dependent manner, but no correlations were noted between number of GFAP-positive
      astrocytes and postmortem time and cause of death. Number of GFAP-positive
      astrocytes in the hippocampus may provide useful information for age estimation.

PMID- 16621652
TI  - Simultaneous determination of pancuronium, vecuronium and their related compounds
      using LC-ESI-MS.
AB  - A simultaneous determination method of quaternary amino steroidal muscle
      relaxants, pancuronium (PAN), vecuronium (VEC), and 17-monodesacetyl pancuronium
      (17-OH-PAN), 3,17-bisdesacetyl pancuronium (3,17-OH-PAN), 3-monodesacetyl
      vecuronium (3-OH-VEC), 3,17-bisdesacetyl vecuronium (3,17-OH-VEC) in human serum
      was developed using liquid chromatography-electrospray ionization-mass
      spectrometry (LC-ESI-MS). The weak cation exchange cartridge was useful for the
      extraction of these compounds. Under optimized LC-ESI-MS conditions, these
      compounds were almost fully separated within 6.5 min. Linear responses over the
      concentration range 0.25-50.0 ng/mL were demonstrated for each compound. The
      developed method successfully detected VEC, 3-OH-VEC and 3,17-OH-VEC in serum
      intravenously administered with VEC. The level of 3-OH-VEC was higher than other
      compounds. This suggested that 3-OH-VEC was useful as a forensic probe in VEC
      administration.

PMID- 16621653
TI  - Sonochemical synthesis of polyaniline nanofibers.
AB  - Conventionally, micro-sized irregular polyaniline (PANI) particles were
      synthesized by dropwise addition of the ammonium persulfate (APS) solution into
      the aniline (ANI) solution with mechanical stirring. By replacing the mechanical
      stirring with an ultrasonic irradiation, PANI nanofibers in diameters of
      approximately 50 nm and lengths of 200 nm to several micrometers were prepared.
      Transmission electron microscopy (TEM) and scanning electron microscopy (SEM)
      showed that at the early stage of polymerization, the polymers formed in both the
      mechanical stirred and ultrasonicated systems are in the form of nanofiber.
      However, with continuing of the reaction, these primary nanofibers grow and
      agglomerate into irregular shaped PANI particles in the mechanical stirred
      system, while in the case of the ultrasonic irradiation, the growth and
      agglomeration are effectively prevented, preserving thus the PANI nanofibers in
      the final product. By increasing the APS/ANI molar ratio from 0.5 to 2.5, the
      aspect ratios of the PANI nanofibers decreased. The PANI nanofibers exhibit
      higher solubility than the irregular shaped PANI particles. Although the yield,
      as well as the conductivity of the ultrasonic synthesized PANI nanofibers, was
      slightly lower than the irregular shaped PANI particles, the ultrasonic synthesis
      approach is one of the facile and scalable approaches in synthesizing PANI
      nanofibers in comparison with other ones without use of templates (e.g., the
      interfacial polymerization and rapid mixing polymerization). UV-Vis and Fourier
      transformed infrared (FTIR) spectra indicated ultrasound had no significant
      effect on the chemical structure of the PANI.

PMID- 16621654
TI  - Preparation of barium strontium titanate Ba(1-x)Sr(x)TiO(3) (0<or= x <or=0.2)
      single-crystal nanorods by a novel combined method.
AB  - An ultrasonic irradiation method was applied to the sol/gel synthesis of the
      single-crystal cubic barium strontium titanate Ba(1-x)Sr(x)TiO(3) (0<or= x
      <or=0.2). The characteristics of the composites were examined by X-ray
      diffraction, thermogravimetric analysis, differential thermal analysis,
      transmission electron microscopy and high-resolution transmission microscopy. The
      diameters and lengths of typical resultant Ba(0.8)Sr(0.2)TiO(3) are in the range
      of 70-100 nm and 650-1000 nm, respectively. In addition, the stoichiometric
      sonogel formation and its heat-treatment process, the relationship between x of
      Ba(1-x)Sr(x)TiO (3) and the crystal structure, the relationship between synthesis
      condition of sonogel and morphology have been discussed.

PMID- 16621655
TI  - A remote data access architecture for home-monitoring health-care applications.
AB  - With the aging of the population and the increasing patient preference for
      receiving care in their own homes, remote home care is one of the fastest growing
      areas of health care in Taiwan and many other countries. Many remote home
      monitoring applications have been developed and implemented to enable both formal
      and informal caregivers to have remote access to patient data so that they can
      respond instantly to any abnormalities of in-home patients. The aim of this
      technology is to give both patients and relatives better control of the health
      care, reduce the burden on informal caregivers and reduce visits to hospitals and
      thus result in a better quality of life for both the patient and his/her family.
      To facilitate their widespread adoption, remote home-monitoring systems take
      advantage of the low-cost features and popularity of the Internet and PCs, but
      are inherently exposed to several security risks, such as virus and denial-of
      service (DoS) attacks. These security threats exist as long as the in-home PC is
      directly accessible by remote-monitoring users over the Internet. The purpose of
      the study reported in this paper was to improve the security of such systems,
      with the proposed architecture aimed at increasing the system availability and
      confidentiality of patient information. A broker server is introduced between the
      remote-monitoring devices and the in-home PCs. This topology removes direct
      access to the in-home PC, and a firewall can be configured to deny all inbound
      connections while the remote home-monitoring application is operating. This
      architecture helps to transfer the security risks from the in-home PC to the
      managed broker server, on which more advanced security measures can be
      implemented. The pros and cons of this novel architecture design are also
      discussed and summarized.

PMID- 16621656
TI  - Objective detection of evoked potentials using a bootstrap technique.
AB  - Evoked potentials are usually evaluated subjectively, by visual inspection, and
      considerable differences between interpretations can occur. Objective, automated
      methods are normally based on calculating one (or more) parameters from the data,
      but only some of these techniques can provide statistical significance (p-values)
      for the presence of a response. In this work, we propose a bootstrap technique to
      provide such p-values, which can be applied to a wide variety of parameters. The
      bootstrap method is based on randomly resampling (with replacement) the original
      data and gives an estimate of the probability that the response obtained is due
      to random variation in the data rather than a physiological response. The method
      is illustrated using auditory brainstem responses (ABRs) to detecting hearing
      thresholds. The flexibility of the approach is illustrated, showing how it can be
      used with different parameters, numbers of stimuli and with user-defined false
      positive rates. The bootstrap method provides a new, simple and yet powerful
      means of detecting evoked potentials, which is very flexible and readily adapted
      to a wide variety of signal parameters.

PMID- 16621657
TI  - An accurate simulation model of anteriorly displaced TMJ discs with and without
      reduction.
AB  - Internal derangement of the temporomandibular joint (TMJ) is defined as an
      abnormal positional relationship of the disc relative to the mandibular condyle
      and the glenoid fossa. Among others, the anterior disc displacement is the most
      common disorder, however its origin and consequences are still unclear. Several
      finite element simulations of the TMJ have been developed, but none of them has
      reported dynamic simulations of the disc as a three-dimensional, fiber-reinforced
      biphasic material under finite deformations, during the opening movement of a
      pathologic joint affected of an anterior displacement of the disc with and
      without reduction, using a realistic geometry of the ligaments in the joint. The
      aim of the work presented here was to compare the stress distribution in the
      healthy joint and in two pathologic situations, one joint affected of an anterior
      disc displacement with reduction (ADDWR) and one without reduction (ADDWOR)
      during an opening movement of the mouth. It was found that, while in the healthy
      disc the highest compressive stresses were located in the intermediate zone, in
      the pathologic joints the maximum compressive stresses were located in the
      posterior band both in the ADDWOR case and in the ADDWR before the reduction.
      Moreover, although the final stress distribution in the ADDWR was similar to that
      in the healthy case, the collateral ligaments supported higher stresses, a fact
      that could lead to degeneration of these components and subsequently to the total
      anterior displacement of the disc. Finally, the results suggest that an anterior
      displacement of the disc would lead to higher compressive and tangential stresses
      in the posterior band of the disc than in the healthy one, and as a consequence,
      to possible perforations in that zone of the disc which would modify its geometry
      if no treatment is applied.

PMID- 16621658
TI  - Responsiveness of impairments and disabilities in Parkinson's disease.
AB  - The objective of this study is to evaluate the responsiveness of items of the
      Activities of Daily Living (ADL) and Motor section of the Unified Parkinson's
      Disease Rating Scale (UPDRS) in patients with Parkinson's Disease (PD). A
      standardized Response Mean (SRM) per item was calculated using data of four
      trials (n=376) that randomised patients with early PD to dopamine agonist (DA)
      monotherapy or placebo. In the ADL section, the SRMs ranged from -0.04 (no
      effect) to -0.50 (moderate effect). Hand functions were the most responsive ADL
      items with 'handwriting' showing the largest response. Self-assessed symptoms
      were the least responsive. In the Motor section, SRMs ranged from -0.09 to -0.60
      with bradykinesia items showing the largest response, especially the item 'finger
      taps'. The tremor items showed the smallest response, however, rest tremor arms
      was much more responsive than rest tremor of the head and legs or postural
      tremor. SRMs in the placebo group ranged from 0.08 to -0.21 in the ADL section
      and from 0.03 to -0.35 in the Motor section. ADL and motor items have comparable
      and mostly small effect sizes. The most responsive items are in the ADL section
      hand functions and in the Motor section bradykinesia items. A more responsive ADL
      section would omit the self-assessed symptoms and the Motor section would retain
      only rest tremor arms of the tremor items.

PMID- 16621659
TI  - Bimanual coordination dysfunction in early, untreated Parkinson's disease.
AB  - Bimanual coordination involves the simultaneous performance of either symmetrical
      (in-phase) or asymmetrical (anti-phase) movements with both hands and is known to
      be impaired in Parkinson's disease (PD). At present, it is unclear whether this
      aspect of motor function is already impaired in early stage, untreated PD
      patients. Therefore, we investigated the accuracy of bimanual coordination in 13
      early stage, untreated PD patients and 13 age- and sex-matched healthy controls.
      Each subject performed bimanual coordination tasks at two different movement
      frequencies (1 and 1.75 Hz) and with two different phase relationships (in-phase
      and anti-phase). The percentage of unsuccessful trials (as a measure of overall
      task performance) in PD patients was significantly higher than in healthy
      subjects. PD patients performed high frequency in-phase and anti-phase bimanual
      coordination tasks less accurately with their non-dominant hand than healthy
      subjects. Furthermore, PD patients had more difficulty than healthy subjects in
      maintaining a constant phase relationship between the hands in the anti-phase
      condition at low movement frequency. This study demonstrates that bimanual
      coordination dysfunction is a very early sign of PD. Bimanual coordination tasks,
      in particular those involving high frequency anti-phase movements, might prove
      useful in the early diagnosis of PD.

PMID- 16621660
TI  - Cardiovascular dysautonomia as a cause of falls in Parkinson's disease.
AB  - Parkinson's disease (PD) patients have a ninefold increased risk of recurring
      falls compared to healthy controls. The risk of falling due to cardiovascular
      dysautonomia (CVD) is not quantifiable. But, CVD is an integral part of the
      disease and at least 20% of PD patients suffer from orthostatic hypotension, an
      expression of CVD. One way to reduce falls due to CVD in PD patients could be to
      give adequate information on the relationship between falling risks and
      cardiovascular dysautonomia to patients and their caregivers. Moreover, drugs
      given for PD might contribute to OH and we propose that education and non
      pharmacological strategies for its treatment might be preferable, especially
      because of the low efficacy of drugs available for the treatment of OH and the
      frailty of elderly PD patients.

PMID- 16621661
TI  - Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson
      disease: a systematic review.
AB  - INTRODUCTION: The long-lasting beneficial effects of subthalamic nucleus (STN)
      deep brain stimulation (DBS) on motor function have now largely been
      acknowledged. Whereas behavioural changes have been demonstrated in certain case
      reports and small case series, some authors have not observed behavioural changes
      at all. The extent to which these changes occur has not yet been established. The
      aim of the present study was to systematically analyse behavioural changes of
      bilateral STN DBS. MATERIALS AND METHODS: A structured Medline search was
      conducted using previously described methods. Studies were selected according to
      specific in- and exclusion criteria. Data on patients, surgical technique,
      outcome and complications were collected and pooled. RESULTS: In total 1,398
      patients who underwent bilateral STN DBS were included. The total cumulative
      follow-up period was 1,480 patient-years. Cognitive problems were seen in 41%,
      depression in 8%, and (hypo)mania in 4% of the patients. Anxiety disorders were
      observed in less than 2%, and personality changes, hypersexuality, apathy,
      anxiety, and aggressiveness were observed in less than 0.5% of the group studied.
      About half of the patients did not experience behavioural changes. CONCLUSION:
      Caregivers should be aware of the extent of these behavioural changes and a
      risk/benefit evaluation should be performed for individual patients.

PMID- 16621662
TI  - Anticipation of onset age in familial Parkinson's disease without SCA gene
      mutations.
AB  - Assessment of a series of 279 cases with Lewy body disease revealed 14 families
      having a family history consistent with autosomal dominant inheritance, eight of
      these with dominant Parkinsonism and six with dominant dementia. Analysis of the
      age at onset and genetic features in these families revealed significant
      anticipation only in a subset of parkinsonian families, with no pathological
      alleles for spinocerebellar ataxias or the common alpha-synuclein or LRRK2 point
      mutations.

PMID- 16621663
TI  - Transplantation of human neural precursor cells in the 6-OHDA lesioned rats:
      effect of immunosuppression with cyclosporine A.
AB  - Neural precursor cells (NPC) may provide a source for restaurative therapy. We
      wanted to study the immunogenic potential of human NPC. We transplanted human
      NPCs with or without cyclosporine A (10 mg/kg) expanded in serum-free conditions
      into the striatum of rats unilaterally lesioned with 6-hydroxydopamine. Four
      months after transplantation, there was significant improvement of amphetamine
      induced rotational behavior 9 non-immunosuppressed (13.1+/-4.9 pre vs 8.5+/-4.0
      after grafting) but nor for 11 animals immunosuppressed with CyA (12.3+/-1.7 vs
      11.3+/-2.8). The number of TH-IR cells was comparable in both groups (1,580+/-700
      vs 1,274+/-295). All grafted animals only showed mild activation of astrocytes
      and macrophages within the graft. There was no evidence for tumor formation.
      Immunosuppression of rats, xenotransplanted with human NPC did not improve graft
      survival or function.

PMID- 16621664
TI  - Disruptions of the fornix fiber in Parkinsonian patients with excessive daytime
      sleepiness.
AB  - BACKGROUND: Although excessive daytime sleepiness (EDS) in Parkinson's disease
      (PD) has received a great deal of attention, the underlying pathological
      mechanism of its development and the relative contributions of brain function to
      this process are poorly understood. OBJECTIVE: To compare the fractional
      anisotropy (FA) values of PD patients with EDS and those without EDS, and to
      investigate the mechanism of EDS in this disease. METHODS: Eleven patients with
      PD with EDS, 26 patients with PD without EDS and 10 controls participated in this
      study. Patients with an ESS (Epworth Sleepiness Scale) score >or=10 were defined
      as having EDS. The FA values of 5 regions of interest (ROI) including the fornix
      were compared between the three groups. RESULTS: There were significant
      reductions in FA values of the fornix fiber in patients with EDS. ESS scores had
      significant correlation with FA values of the fornix. CONCLUSIONS: Our study is
      the first to find the fornix fiber degeneration in PD patients with EDS. These
      results indicate that fornix dysfunction may have some correlations with EDS in
      PD.

PMID- 16621665
TI  - Maternal social capital and child nutritional status in four developing
      countries.
AB  - Social capital has been shown to be positively associated with a range of health
      outcomes, yet no studies have explored the association between maternal social
      capital and child nutritional status. Using data from the Young Lives study
      comprising 7242 1-year-old children from Peru, Ethiopia, Vietnam and the state of
      Andhra Pradesh in India, we find significant differences in the levels of, in
      particular, structural social capital (group membership and citizenship) between
      countries. While few associations were found between structural measures of
      social capital, support from individuals and cognitive social capital (e.g.
      trust, social harmony) displayed fairly consistent positive associations with
      child nutritional status across countries.

PMID- 16621666
TI  - BMI, auto use, and the urban environment in San Francisco.
AB  - The epidemic of overweight and obesity has sparked interest in urban planning
      circles. Many believe the built environment directly influences physical health,
      and recent empirical evidence supports this notion. Cross-sectional survey data
      was collected from a sample of San Francisco residents (n=670) in the summer of
      2005. Body mass index (BMI) served as the dependent variable. Independent
      variables included population density and auto use. Results indicate an inverse
      relationship between density and auto use as well as higher BMI scores for
      respondents reporting high levels of auto use for the work/school commute and
      trips to the grocery store.

PMID- 16621667
TI  - Lumbar spine reposition sense: the effect of a 'slouched' posture.
AB  - Proprioceptive control is considered important for spinal stability and
      prevention of injury. However there is evidence that proprioceptive structures,
      that are reflexive and viscoelastic, are challenged by commonly adopted
      'slouched' postures. The aim of this study was to investigate the effect of such
      postures on proprioceptive control. The reliability of a flexible
      electrogoniometer was established (ICC=0.89). Using a repeated measures design
      (n=32, 80% power detecting 0.5 degrees difference at 95% significance) subjects
      repositioned their lumbar spine immediately (3 s) and following 300 s in a
      'slouched' posture, with a 15-min interval in between. Results showed a
      significantly reduced lumbar spine reposition sense following 300 s in a
      'slouched' posture as compared with 3 s in a 'slouched' posture (P<0.001), mean
      difference 3.92 degrees (SD 4.35). Based on this sample, there was evidence that
      a 'slouched' posture, of 5 min duration, would increase reposition error by more
      than 2.35 degrees and less than 5.48 degrees (n=32, CI 95%). These findings
      support the practice of postural education to reduce potential to proprioceptive
      loss and injury. The electrogoniometer shows potential for use in clinical
      practice.

PMID- 16621668
TI  - Immediate effects of thoracic manipulation in patients with neck pain: a
      randomized clinical trial.

PMID- 16621669
TI  - Cells of the anterior pituitary.
AB  - The anterior pituitary is made up of a number of cell types that are essential
      for such physiological processes as growth, development, homeostasis, metabolism,
      and reproduction. These include the hormonal cells corticotropes, thyrotropes,
      gonadotropes, somatotropes, lactotropes and a small population of
      mammosomatotropes, together with a non-hormonal cell type called the folliculo
      stellate cells. The anterior pituitary hormonal cells are highly differentiated
      and are committed very early on during embryonic development. Their development
      is tightly regulated by both extrinsic signals as well as by endogenous gene
      expression. Many transcription factors that shape the development and functions
      of the anterior pituitary cells have been identified. Even after differentiation,
      pituitary cells continue to undergo mitosis and this process could be augmented
      under certain conditions in adulthood. Some anterior pituitary cells are
      multifunctional and exhibit mixed phenotypes. Pituitary tumors, which are mostly
      monoclonal in nature, are rather common. The molecular pathogenesis of pituitary
      tumorigenesis involves complex and diverse mechanisms. Aberrant intra- and extra
      pituitary factors are involved. Mutations of some genes specific to pituitary
      tumors also play a role.

PMID- 16621670
TI  - An overview of lipid peroxidation with emphasis in outer segments of
      photoreceptors and the chemiluminescence assay.
AB  - The onset of lipid peroxidation within cellular membranes is associated with
      changes in their physicochemical properties and with the impairment of protein
      functions located in the membrane environment. This article provides current
      information on the origin and function of polyunsaturated fatty acids in nature,
      lipid peroxidation of cellular membranes: enzymatic (lipoxygenases) and non
      enzymatic. The latest knowledge on in vivo biomarkers of lipid peroxidation
      including isoprostanes, isofurans and neuroprostanes are discussed. A further
      focus is placed on analytical methods for studying lipid peroxidation in
      membranes with emphasis in chemiluminescence and its origin, rod outer segments
      of photoreceptors, the effect of antioxidants, fatty acid hydroperoxides and
      lipid protein modifications. Since rhodopsin, the major integral protein of rod
      outer segments is surrounded by phospholipids highly enriched in docosahexaenoic
      acid, the author proposes the outer segments of photoreceptors as an excellent
      model to study lipid peroxidation using the chemiluminescence assay since these
      membranes contain the highest concentration of polyunsaturated fatty acids of any
      vertebrate tissue and are highly susceptible to oxidative damage.

PMID- 16621671
TI  - Regulation of apoptosis by insulin-like growth factor (IGF)-I.
AB  - IGF-I is important for fetal and post-natal development, but it also controls
      tissue homeostasis throughout life via regulation of cell proliferation and
      apoptosis. This review summarizes our current understanding of how IGF-I receptor
      signaling interferes with the apoptotic machinery of the cell. IGF-I acts at
      different control points of apoptosis, including the Bcl-2 family proteins,
      inhibitors of caspases and signaling of death-inducing receptors. The main focal
      point of IGF-I is the regulation of Bcl-2 family proteins. Several signaling
      pathways converge to both the phosphorylation and transcriptional regulation of
      these proteins. This phenomenon may explain the efficacy of IGF-I as an inhibitor
      of apoptosis in many different cell types and in the presence of different
      apoptogenic stimuli.

PMID- 16621672
TI  - Potato in the age of biotechnology.
AB  - Biotechnology-based tools are now widely used to enhance and expand the
      traditional remit of potato in food production. By modifying its functionality,
      the capacity of the potato to produce, for example, therapeutic or industrial
      compounds is now a reality, and its ability to resist disease can also be
      radically improved. Two developments have been crucial to expanding the role of
      potato: the recent advances in the fields of structural and functional potato
      genomics and the ability to integrate genes of interest into the potato genome.
      In this review we discuss how both developments have diversified the remit of
      this crop.

PMID- 16621674
TI  - Evaluation of povidone-iodine as a disinfectant solution for contact lenses:
      antimicrobial activity and cytotoxicity for corneal epithelial cells.
AB  - Povidone-iodine (PVP-I) possesses broad-spectrum antimicrobial activity and is
      used clinically as a disinfectant. We evaluated the disinfectant properties and
      safety of PVP-I for use as a contact lens solution. The concentrations of PVP-I
      required to reduce the number of Staphylococcus aureus or Candida albicans by 3
      log units were lower than were those of hydrogen peroxide, polyhexamethylene
      biguanide (PHMB), and benzalkonium chloride (BAK). The cytotoxicity of PVP-I for
      cultured human corneal epithelial (HCE) cells was less than that of the other
      three agents. The safety margin for PVP-I was thus greatest among the tested
      compounds. PVP-I appears suited for use as a contact lens disinfectant.

PMID- 16621675
TI  - Aptamer therapeutics advance.
AB  - Aptamers are selected nucleic acid binding species with affinities and
      specificities for protein targets that rival those of monoclonal antibodies.
      Furthermore, aptamers have definite advantages over antibodies, in that they can
      be chemically synthesized and modifications can be introduced that improve their
      stabilities and pharmacokinetic properties. A number of aptamers against
      therapeutically important targets have shown efficacy in cell and animal models,
      and a handful of aptamers are now in clinical trials or are being used as drugs.
      Recent advances in selection technologies and a more thorough exploration of how
      to deliver nucleic acids to target cells and tissues should further speed the
      process of drug development.

PMID- 16621676
TI  - Tyrosine kinase inhibitors and gemcitabine: new treatment options in pancreatic
      cancer?
AB  - Pancreatic cancer (PCa) is one of the most lethal malignancies in humans.
      Gemcitabine is the current standard chemotherapy of advanced PCa but it is still
      far from optimal and novel therapeutic strategies are urgently needed. For the
      near future, tyrosine kinase inhibitors (TKIs) hold great promise as a
      therapeutic strategy. Tyrosine kinases (TKs) play a pivotal role in intercellular
      signal transduction and regulate crucial processes of tumor cells such as
      proliferation, migration, survival and angiogenesis. Several TKs--such as EGFR,
      VEGFR, PDGFR and Src--are known to be overexpressed or constitutively activated
      in PCa. Hence, blocking receptor tyrosine kinases (RTKs) and non-receptor,
      cytoplasmic tyrosine kinases (CTKs) represents a rational approach to treat PCa.
      In particular, cetuximab and erlotinib, the monoclonal antibodies against EGFR-1
      (ErbB-1) showed promising activity in Phase II and Phase III trials and their
      combination with gemcitabine resulted in synergistic antitumor activity. In
      addition, small antiangiogenic molecules such as VEGFR-2 inhibitors, PDGFR
      inhibitors and multiple receptor targeting agents are under active investigation.
      Association of chemoresistance with the activity of certain tyrosine kinases
      (e.g. ErbB-1 and Src) has been described for pancreatic cancer and makes a strong
      case for combining gemcitabine with TKIs. Combinations of different TKIs might
      also be used to target the cancer cell micro-environment. Detailed molecular
      characterization of tumor cells and combinations of appropriate TKIs with
      cytotoxic agents such as gemcitabine are expected to lead to improved therapy of
      pancreatic cancer.

PMID- 16621677
TI  - Tumor-specific nuclear targeting: promises for anti-cancer therapy?
AB  - Recent developments in anti-cancer gene therapy suggest that the idea of a magic
      bullet for cancer may not be a pipe dream. Viral-based anti-cancer vectors for
      gene therapy have been used preferentially in this regard, but recent results
      from clinical trials have raised serious concerns as to their safety. For this
      reason, the development of non-viral vectors able to deliver drugs or suicide
      genes specifically to cancer cells is of paramount importance. In this context,
      great interest has been raised by recent reports that several proteins, including
      viral protein 3 (VP3 or Apoptin) from Chicken Anemia Virus, are capable of
      selectively killing tumor cells. Intriguingly, VP3's anti-cancer activity is
      strongly linked to its ability to localize more efficiently in the nucleus of
      cancer and transformed cells than that of normal, non-transformed cells with a
      tumor cell-specific nuclear targeting signal (tNTS) located at the C-terminus of
      the protein. Clearly, the VP3 tNTS is an exciting prospect to enhance non-viral
      mediated cancer cell killing. This review will discuss recent advances in the
      understanding of the mechanism responsible for VP3 tumor-specific nuclear
      localization, including its specific phosphorylation, and the implications for
      the enhancement of anti-cancer therapy. It also proposes alternative strategies
      to develop tNTSs for anti-cancer therapies.

PMID- 16621678
TI  - Directed evolution of enzymes and biosynthetic pathways.
AB  - Directed evolution is an important tool for overcoming the limitations of natural
      enzymes as biocatalysts. Recent advances have focused on applying directed
      evolution to a variety of enzymes, such as epoxide hydrolase, glyphosate N
      acetyltransferase, xylanase and phosphotriesterase, in order to improve their
      activity, selectivity, stability and solubility. The focus has also shifted to
      manipulating biosynthetic pathways for the production of many naturally
      synthesized compounds, as well as the production of novel 'unnatural' compounds.
      A combined directed evolution and computational design approach is becoming
      increasingly important in exploring enzyme sequence-space and creating improved
      or novel enzymes. Fueled by recent breakthroughs in genomics and metagenomics,
      these developments should help expand the use of biocatalysts in industry.

PMID- 16621679
TI  - Basal and induced micronucleus frequencies in human lymphocytes with different
      GST and NAT2 genetic backgrounds.
AB  - Basal and induced frequencies of genetic damage can be modulated by different
      host factors, including genes involved in phase II metabolism. Since polymorphic
      variants in the glutathione S-transferase (GST) and N-acetyl transferase (NAT)
      genes have been associated with cancer risk, we explored the possible links
      between GSTM1, GSTP1, GSTT1 and NAT2 variants and the frequency of micronuclei
      (MN) in human lymphocytes. This exploratory study was carried out in 30 thyroid
      cancer patients, before and after receiving an average dose of 109.9+/-1.3 mCi
      radioactive iodine as a co-adjuvant therapy. The results indicate that none of
      the polymorphisms studied show any kind of association with the basal level of
      micronuclei. When the same patients were followed after radioiodine exposure, a
      significant increase in the frequency of MN was observed in practically all of
      them (28/30), indicating the genotoxic activity of the ionising radiation
      exposure. The increase in MN frequency was not associated with any of the GST
      polymorphisms evaluated. Nevertheless, the presence of slow acetylator phenotypes
      and, in particular, the presence of the NAT2*7 allele was significantly
      associated with a lower increase of the MN frequency after radioiodine treatment.

PMID- 16621680
TI  - Reliable Comet assay measurements for detecting DNA damage induced by ionising
      radiation and chemicals.
AB  - The alkaline version of the single cell gel electrophoresis assay, popularly
      known as the Comet assay, is widely used to evaluate the genotoxic potential of
      chemicals and environmental contaminants, and for environmental monitoring
      purposes. In recent years, this assay has increasingly been recognized as a
      potentially valuable tool for regulatory studies. The assay commonly utilises
      commercially available software programmes to evaluate the extent of DNA damage
      at the single-cell level. These programmes provide a large number of measurement
      outcomes (i.e., tail length, %Tail DNA, various measures of tail moment, etc.) to
      evaluate the extent of DNA migration and DNA damage. At the moment, however,
      there is no general agreement with respect to the most relevant measurements or
      parameters to use. This study was carried out to establish which measurement(s)
      in the Comet assay are most significantly correlated with DNA damage, and should
      thus be adopted for routine use. Pooled peripheral blood samples from 3 healthy
      human individuals were irradiated with a range of doses of (137)Cs gamma
      radiation (0, 1, 2, 4 and 8 Gy). Following irradiation, the Comet assay was
      performed according to a standard protocol, and different parameters were
      recorded by use of Komet 5.0 software (Kinetic Imaging Ltd., Liverpool, UK).
      Following a correlation analysis, the Olive Tail Moment (OTM), the Tail Extent
      Moment and the percentage of DNA in the tail (%Tail DNA) gave good correlations
      that were not significantly different from each other. Further retrospective
      analysis from other in vitro and in vivo Comet assay experiments with chemical
      agents also suggested that OTM and %Tail DNA gave good correlation with the dose
      of genotoxic agents used. Since OTM and %Tail DNA are the most commonly used
      parameters in many manuscripts, these two could continue to be applied for
      routine use. However, since OTM is measured in arbitrary units and different
      image-analysis systems give different values, the %Tail DNA could be considered
      more meaningful and easy to conceptualise. Other parameters might not be
      considered of significant use in genotoxicological studies.

PMID- 16621681
TI  - Propagation of program control: a tool for distributed disease surveillance.
AB  - PURPOSE: The purpose of the study was (1) to identify the requirements for
      syndromic, disease surveillance and epidemiology systems arising from events such
      as the SARS outbreak in March 2003, and the deliberate spread of Bacillus
      anthracis, or anthrax, in the US in 2001; and (2) to use these specifications as
      input to the construction of a system intended to meet these requirements. An
      important goal was to provide information about the diffusion of a communicable
      disease without being dependent on centralised storage of information about
      individual patients or revealing patient-identifiable information. METHODS: The
      method applied is rooted in the engineering paradigm involving phases of
      analysis, system specification, design, implementation, and testing. The
      requirements were established from earlier projects' conclusions and analysis of
      disease outbreaks. The requirements were validated by a literature study of
      syndromic and disease surveillance systems. The system was tested on simulated
      EHR databases generated from microbiology laboratory data. RESULTS: A
      requirements list that a syndromic and disease surveillance system should meet,
      and an open source system, "The Snow Agent system", has been developed. The Snow
      Agent system is a distributed system for monitoring the status of a population's
      health by distributing processes to, and extracting epidemiological data directly
      from, the electronic health records (EHR) system in a geographic area.
      CONCLUSIONS: Syndromic and disease surveillance tools should be able to operate
      at all levels in the health systems and across national borders. Such systems
      should avoid transferring patient identifiable data, support two-way
      communications and be able to define and incorporate new and unknown diseases and
      syndrome definitions that should be reported by the system. The initial tests of
      the Snow Agent system shows that it will easily scale to national level in
      Norway.

PMID- 16621682
TI  - Championing telemedicine adoption and utilization in healthcare organizations in
      New Zealand.
AB  - BACKGROUND/OBJECTIVES: This research explored the adoption and the utilisation of
      telemedicine (TM) in two healthcare organizations (HCOs) in New Zealand (NZ). The
      research utilised the technological innovation theories, as a guiding theoretical
      framework, to develop a set of potential determinants which could assist in
      understanding the adoption and the depth of the TM phenomenon in the two HCOs.
      METHODOLOGY AND RESULTS: Using case studies design, the findings across the two
      cases revealed that TM was adopted according to its cost-benefit analysis.
      Although this approach was found to be important in assessing the adoption of TM,
      not considering the importance of other factors, highlighted in this research,
      such as the compatibility and the trialability aspects of the TM technology had a
      detrimental impact on the success of TM in both cases. CONCLUSION: This research
      stressed the need for the tight coupling between the roles of both the
      administrative and the clinical managers in HCOs in order to champion TM adoption
      and diffusion and to overcome many of the barriers that could hinder telemedicine
      success in HCOs in NZ. The research points to other implications with respect to
      the literature and highlights further research in this important area.

PMID- 16621683
TI  - Design and implementation of a point-of-care computerized system for drug therapy
      in Stockholm metropolitan health region--Bridging the gap between knowledge and
      practice.
AB  - INTRODUCTION: Stockholm County Council is the largest health care provider in
      Sweden with an annual budget of US$ 5 billion and catering the needs of a
      metropolitan population of 2 million people. About 10% of health care costs are
      used on drugs. In 1996 Stockholm County Council decided to address the main
      problems associated with the process and the quality of drug prescribing.
      METHODS: A multiyear strategy was designed, including the establishment of a
      strong evidence-based organisation, Drug and Therapeutics Committees and
      editorial resources to adapt information to the IT-media and the development of
      the IT-architecture. The development and implementation of computerized tools
      such as a physician drug order entry system including decision support, a drug
      information website and electronic transmission of prescriptions were started in
      1996. RESULTS: The implementation was slow at the point-of-care units. It took
      about 6 years before the implementation process gained speed. In September 2005
      almost 1000 doctors could use the decision support system for prescribing drugs
      and more than 70% of all prescriptions were transmitted electronically in our
      region. CONCLUSIONS: The work with the strategy has shown that improvements in
      drug use can be accomplished by providing access to simple, rapid and safe
      electronic tools, but the information provided has to be associated with well
      recognized regional and national expert organisations.

PMID- 16621684
TI  - Computer-aided detection of prostate cancer.
AB  - BACKGROUND: Prostate cancer is one of the most frequent cancers in men and is a
      major cause of mortality in developed countries. Detection of prostate carcinoma
      at an early stage is crucial for successful treatment. MATERIAL AND METHODS: A
      method for the analysis of transrectal ultrasound images aimed at computer-aided
      diagnosis of prostate cancer is tested in this paper. First, two classifiers
      based on k-nearest neighbors and Hidden Markov models are compared. Second, the
      diagnostic capacity of our system is tested by means of a set of experiments
      where humans with varying degrees of experience classified a set of ultrasound
      images with and without the aid of the computer-aided system. The corpus used in
      this study was specifically acquired for this purpose. It consists of 4944
      ultrasound images corresponding to 303 patients, and is publicly available for
      non-commercial use upon request. RESULTS: The best classification results achieve
      an area under the receiver operating characteristic curve of 61.6%. However, the
      diagnostic capacity of an expert urologist using the computer-aided system
      improves only slightly compared with his/her capacity without the aid of the
      system. CONCLUSIONS: Despite the difficulty of this task, the obtained results
      indicate that discrimination between cancerous and non-cancerous tissue is
      possible to a certain degree. The computer-aided system helps an inexperienced
      user to make a better diagnosis, however it must be able to perform better in
      order to be useful in a real-world clinical context.

PMID- 16621685
TI  - Hepatitis B virus genotypes in acute and fulminant hepatitis patients from north
      India using two different molecular genotyping approaches.
AB  - Data from India on hepatitis B virus (HBV) genotype related differences in
      clinical progression and outcome of acute and fulminant hepatitis B are limited.
      Sera from patients with acute hepatitis B (AHB) (n=80), fulminant hepatitis B
      (FHB) (n=40) and asymptomatic HBsAg carriers (ASC) (n=40) were tested for HBV
      genotype using polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and type-specific primers-based PCR (TSP-PCR). The genotype
      distribution for 160 patients with HBV related hepatitis/carriers were as
      follows: A, 3/80 (3.7%) in AHB, 2/40 (5%) in FHB and 7/40 (17.5%) in ASC; D,
      77/80 (96.2%) in AHB, 38/40 (95%) in FHB and 33/40 (82.5%) in ASC. C, 0; B, 0; E,
      0; F, 0 (p<0.01, genotype D versus A). Compared with genotype D, genotype A
      patients had no significant clinical or biochemical differences (p>0.05). HBV
      genotypes A and D were found to be prevalent in patients with HBV related acute
      and fulminant hepatitis from New Delhi, India. Genotype D was the dominant
      genotype prevalent in all patient categories while genotype A was solely
      responsible for AHB leading to chronic hepatitis B in 3.7% of the cases from this
      region.

PMID- 16621686
TI  - A case-control study of response to lamivudine therapy for 2 years in Japanese
      and Chinese patients chronically infected with hepatitis B virus of genotypes Bj,
      Ba and C.
AB  - BACKGROUND/AIMS: In eastern Asian countries, hepatitis B virus (HBV) genotype Ba
      (HBV/Ba), HBV/Bj and HBV/C are prevalent. The aim was to investigate the response
      or resistance to lamivudine therapy among patients with different HBV genotypes.
      METHODS: Of 67 Japanese and Chinese patients with chronic hepatitis B, 18
      patients with HBV/Bj, 15 with HBV/Ba and 34 with HBV/C were selected for a case
      control study matched according to gender and age. All the patients were treated
      with lamivudine for 2 years and evaluated the response or emergence of the YMDD
      mutation at year 2 during the treatment. HBV genotypes were detected by the
      restriction fragment length polymorphism. The YMDD mutation was detected by the
      direct sequencing after amplification by PCR. RESULTS: At year 2 during therapy,
      44.8% of the patients showed normalization of ALT and undetectable HBV DNA
      (favorable response), 35.8% developed the YMDD mutation. There was no significant
      difference of response to the therapy among the three genotype groups. The
      emergence of the YMDD mutation was associated with HBV/C. By the multiple
      logistic regression analysis, however, the significant factor of a favorable
      response was a higher pretreatment ALT level and negative HBeAg status and the
      significant factor of the emergence of the YMDD mutation was HBV/C. CONCLUSIONS:
      Higher pretreatment ALT level, HBeAg status or HBV genotype may affect the
      response or resistance to lamivudine therapy.

PMID- 16621687
TI  - Cytoskeletal reorganization and repolarization of hepatocarcinoma cells in APA
      microcapsule to mimic native tumor characteristics.
AB  - Culture of human hepatocarcinoma cells in three-dimensional structure or spheroid
      represents a unique opportunity to recapitulate aspects of cell homeostasis and
      to better reflect the characteristics of native hepatic tumor. In this paper,
      human hepatocarcinoma SMMC-7721 cells were encapsulated in alginate-poly-l-lysine
      alginate (APA) microcapsules and the behavior of the cells in the restricted
      three-dimensional culture system was investigated. The cells were polygonal
      shaped, proliferating with high viability, and formed a single multicellular
      spheroid in microcapsule. During the assembly of the aggregate in microcapsule,
      cytoskeletal reorganization and repolorization was occurred, which was absent in
      cells cultured in monolayer. The in vivo-like cytoarchitecture was confirmed by
      the phalloidin-FITC labeling of F-actin filaments. The trabecular structure
      revealed by scanning electron microscope (SEM), and the bile canaliculus with
      multiple microvilli and tight junctions revealed by transmission electron
      microscope (TEM) was found in microencapsulated cells, which exhibited the
      ultrastructural characteristics of native hepatic tissue. It suggested that
      microcapsule culture provides an in vivo-like model which can be used for the
      study of the interactions of cell-cell and cell-microenvironment, and the
      mechanisms of invasion, metastasis and multicellular drug resistance of tumor
      cells.

PMID- 16621688
TI  - Assembly of biliary lipids in native hepatic bile after orthotopic liver
      transplantation: A biochemical and ultra-structural study in humans.
AB  - BACKGROUND: In gallbladder bile, lipids aggregate as micelles and vesicles, yet
      the presence of lamellae remains controversial. Little is known on lipid assembly
      in dilute hepatic bile. Liver transplantation represents a condition in which
      bile is diluted immediately after transplant and tends to normalize thereafter.
      AIM: To study biliary lipidic carriers after liver transplantation in relation to
      the increasing bile lipid concentration. METHODS: Three bile samples were
      harvested from six patients (3M/3F) with normal post-transplant outcome: sample 1
      at days 2-3, sample 2 at 1 week, and sample 3 at 2 weeks after transplant.
      Samples were analyzed by biochemical, morphological and quasi-elastic light
      scattering methodology. RESULTS: Lipid concentration increased from 0.6g/dl at
      day 2-3 to 3.6g/dl at week 2. Electron microscopy showed the presence of
      unilamellar vesicles in all samples. Large amorphous particles interpreted as
      proteic aggregates were also present at day 2-3, while lamellae coexisted with
      vesicles later. Quasi-elastic light scattering data were consistent with electron
      microscopic findings. Liquid crystals were observed at polarizing microscopy with
      increasing bile lipid concentration. CONCLUSIONS: Normalization of biliary lipid
      secretion after liver transplantation is associated with: (i) increased
      proportion of vesicles and reduction of their size; (ii) presence of lamellae.

PMID- 16621689
TI  - Phylogenetic analysis of hepatitis E virus isolates in southern China (1994
      1998).
AB  - BACKGROUND: We have previously reported the identification of divergent hepatitis
      E virus (HEV) isolated (G9, G20 and 93G) in Guangzhou, a city in southern China.
      They are now recognised as a new HEV subgenotype in the world. However, the
      relatedness and significance of these novel isolates in sporadic HEV infection in
      southern China is still unclear. OBJECTIVES: To perform phylogenetic analysis of
      nucleotide sequences from 41 HEV isolates in southern China from 1994 to 1998.
      STUDY DESIGN: The partial nucleotide sequence of the HEV isolates were determined
      and compared with reported sequences in the GenBank. Their relatedness was
      analysed using computer software. RESULTS: The majority of the HEV isolates, 39
      out of 41, were found to belong to the Burmese-like isolates (genotype 1). The
      other two belonged to the Guangzhou-like isolates. The latter were only found in
      the samples collected in 1994. They, together with the G9 isolate, form a unique
      tree located between genotype 1 and genotype 4 (divergent HEV strains from
      northern China and Taiwan) on the phylogenetic tree. CONCLUSION: Our results
      suggest that the Burmese-like isolates are the main causative agents of sporadic
      HEV infection in southern China. The Guangzhou-like isolates, which appeared
      transiently in 1994, did not seem to adapt to the environment and have caused no
      sporadic infection since.

PMID- 16621690
TI  - Seizure detection algorithm for neonates based on wave-sequence analysis.
AB  - OBJECTIVE: The description and evaluation of the performance of a new real-time
      seizure detection algorithm in the newborn infant. METHODS: The algorithm
      includes parallel fragmentation of EEG signal into waves; wave-feature extraction
      and averaging; elementary, preliminary and final detection. The algorithm detects
      EEG waves with heightened regularity, using wave intervals, amplitudes and
      shapes. The performance of the algorithm was assessed with the use of event-based
      and liberal and conservative time-based approaches and compared with the
      performance of Gotman's and Liu's algorithms. RESULTS: The algorithm was assessed
      on multi-channel EEG records of 55 neonates including 17 with seizures. The
      algorithm showed sensitivities ranging 83-95% with positive predictive values
      (PPV) 48-77%. There were 2.0 false positive detections per hour. In comparison,
      Gotman's algorithm (with 30s gap-closing procedure) displayed sensitivities of 45
      88% and PPV 29-56%; with 7.4 false positives per hour and Liu's algorithm
      displayed sensitivities of 96-99%, and PPV 10-25%; with 15.7 false positives per
      hour. CONCLUSIONS: The wave-sequence analysis based algorithm displayed higher
      sensitivity, higher PPV and a substantially lower level of false positives than
      two previously published algorithms. SIGNIFICANCE: The proposed algorithm
      provides a basis for major improvements in neonatal seizure detection and
      monitoring.

PMID- 16621691
TI  - Dose-response relationship between the H-reflex and continuous intrathecal
      baclofen administration for management of spasticity.
AB  - OBJECTIVE: To determine the relationship between the H-reflex (H/M ratio) and
      continuous intrathecal baclofen (CITB) dose after pump implantation for control
      of spastic hypertonia. METHODS: Soleus H-reflexes were serially recorded in 34
      subjects (19 men, mean age 32 years, mean follow-up 1.7 years) during simple
      continuous mode of CITB delivery. Different fitting methods were explored to
      determine which function best described changes in H/M ratio with increasing CITB
      dose. We then calculated effective CITB doses yielding H/M ratios equal to 75,
      50, and 25% (ED75, ED50, ED25) of the baseline recorded before the implant in 22
      subjects. RESULTS: We found a significant dose-response relationship between the
      soleus H/M ratio and CITB dose. A two-decay exponential function was the best fit
      on each side for pooled data, but a general linear model when controlling for
      subject. The mean ED75, ED50, ED25 were 30, 70, and 110 mcg/day. Logistical
      regression predicted with high probability that the H/M ratio should be less than
      30% at CITB doses above 150 mcg/day. CONCLUSIONS: H/M ratio is strongly dependent
      on CITB dose. It sharply decreases up to 150 mcg/day of CITB followed by a
      plateau. SIGNIFICANCE: Establishing the relationship between the H/M ratio and
      CITB dose may be useful for dose titration and early identification of an ITB
      system malfunction.

PMID- 16621692
TI  - Bridging function and structure of the neuromuscular system.

PMID- 16621693
TI  - The regulation of carbon and nutrient assimilation in diatoms is significantly
      different from green algae.

PMID- 16621694
TI  - Phylogenetic analysis of coccidian parasites from invertebrates: search for
      missing links.
AB  - Apicomplexan parasites represent one of the most important groups of parasitic
      unicellular eukaryotes comprising such important human parasites such as
      Plasmodium spp. and Toxoplasma gondii. Apicomplexan radiation as well as their
      adaptation to the parasitic style of life took place before the era of
      vertebrates. Thus, invertebrates were the first hosts of apicomplexan parasites
      that switched to vertebrates later in evolution. Despite this fact, apicomplexan
      parasites of invertebrates, with the exception of gregarines, have so far been
      ignored in phylogenetic studies. To address this issue, we sequenced the nuclear
      SSU rRNA genes from the homoxenous apicomplexan parasites of insects Adelina
      grylli and Adelina dimidiata, and the heteroxenous Aggregata octopiana and
      Aggregata eberthii that are transmitted between cephalopods and crustaceans, and
      used them for phylogenetic reconstructions. The position of the adelinids as a
      sister group to Hepatozoon spp. within the suborder Adeleorina was stable
      regardless of the phylogenetic method used. In contrast, both members of the
      genus Aggregata possess highly divergent SSU rRNA genes with an unusual
      nucleotide composition. Because of this, they form the longest branches in the
      tree and their position is variable. However, the genus Aggregata branches
      together with adelinids and hepatozoons in most of the analyses, although their
      position within the scope of this cluster is unstable.

PMID- 16621695
TI  - Cloning and characterization of a new multi-stress inducible metallothionein gene
      in Tetrahymena pyriformis.
AB  - A new multi-stress-inducible metallothionein (MT) gene isoform has been cloned
      and characterized from the ciliate Tetrahymena pyriformis. Both the 5'- and 3'-UT
      regions of the Tp-MT2 gene are very different from the previously reported Tp-MT1
      isoform in this organism and from other described MT genes in Tetrahymena
      pigmentosa and Tetrahymena thermophila. The putative protein sequence of Tp-MT2
      contains cysteine clusters with characteristics of the typical Tetrahymena Cd
      inducible MT genes. However, the sequence has a special feature of four
      intragenic tandem repeats within its first half, with a conserved structural
      pattern x(5/8)CCCx(6)CCx(6)CxCxNCxCCK. To investigate the transcriptional
      activities of both Tp-MT2 and Tp-MT1 genes toward heavy metals (Cd, Hg, Cu, Zn)
      and H(2)O(2), the mRNA levels of these two isoforms were evaluated by means of
      real-time quantitative PCR. Results showed that Tp-MT2 had a higher basal
      expression level than Tp-MT1 and both genes were induced by Cd, Hg, Cu, and Zn
      ions after short exposure (1h), although to different extents. Cd was the most
      effective metal inducer of both two isoforms, but the relative expression level
      of Tp-MT2 was much lower than that of Tp-MT1. Different expression patterns were
      also shown between the two genes when treated with Cd over a period of 24h. We
      suggest that TpMT-1 plays the role of a multi-inducible stress gene, while TpMT-2
      may have a more specific function in basal metal homeostasis although it may have
      undergone a functional differentiation process. The putative functional
      significance and evolutionary mode of the TpMT-2 isoform are discussed.

PMID- 16621696
TI  - Fabius Gross (1906-1950), a protistologist almost lost from history.

PMID- 16621697
TI  - Mycosporine-like amino acids in the zooxanthella-ciliate symbiosis Maristentor
      dinoferus.
AB  - Coral reef organisms living in mutualistic symbioses with phototrophic
      dinoflagellates are widespread in shallow UV-transparent waters. Maristentor
      dinoferus is a recently discovered species of marine benthic ciliate that hosts
      symbiotic dinoflagellates of the genus Symbiodinium. In this study, we tested
      this ciliate for the occurrence of mycosporine-like amino acids, a family of
      secondary metabolites that minimize damage from exposure to solar UV radiation by
      direct screening. Using high-performance liquid chromatography and liquid
      chromatography coupled to mass spectrometry, five mycosporine-like amino acids
      (shinorine, palythenic acid, palythine, mycosporine-2-glycine, and porphyra-334)
      were identified in aqueous methanolic extracts of the symbiosis. This is the
      first report of mycosporine-like amino acids in a marine ciliate.

PMID- 16621699
TI  - Measurement properties of the CHAMPS physical activity questionnaire in a sample
      of older Australians.
AB  - BACKGROUND: The effective evaluation of physical activity interventions for older
      adults requires measurement instruments with acceptable psychometric properties
      that are sufficiently sensitive to detect changes in this population. AIM: To
      assess the measurement properties (reliability and validity) of the Community
      Healthy Activities Model Program for Seniors (CHAMPS) questionnaire in a sample
      of older Australians. METHODS: CHAMPS data were collected from 167 older adults
      (mean age 79.1 S.D. 6.3 years) and validated with tests of physical ability and
      the SF-12 measures of physical and mental health. Responses from a sub-sample of
      43 older adults were used to assess 1-week test-retest reliability. RESULTS:
      Approximately 25% of participants needed assistance to complete the CHAMPS
      questionnaire. There were low but significant correlations between the CHAMPS
      scores and the physical performance measures (rho=0.14-0.32) and the physical
      health scale of the SF-12 (rho=0.12-0.24). Reliability coefficients were highest
      for moderate-intensity (ICC=0.81-0.88) and lowest for vigorous-intensity physical
      activity (ICC=0.34-0.45). Agreement between test-retest estimates of sufficient
      physical activity for health benefits (> or =150min and > or =5 sessions per
      week) was high (percent agreement=88% and Cohen's kappa=0.68). CONCLUSION: These
      findings suggest that the CHAMPS questionnaire has acceptable measurement
      properties, and is therefore suitable for use among older Australian adults, as
      long as adequate assistance is provided during administration.

PMID- 16621698
TI  - Nontyphoidal Salmonella causing focal infections in patients admitted at a
      Spanish general hospital during an 11-year period (1991-2001).
AB  - In focal infections (FI) caused by nontyphoidal Salmonella serotypes and recorded
      at a Spanish hospital 1991-2001, clinical and microbiological features were
      analyzed. Thirty-five revised episodes were related to infections of the
      digestive (10), urinary (10), pulmonar (4), vascular (4), osteoarticular (3) and
      central nervous (3) systems, and with a submaxillary lymph node. At least 16
      episodes were associated with previous or concomitant gastroenteritis, 19 with
      primary or secondary bacteremia, and 18 with underlying diseases of different
      severity. Eighteen patients were male and 14 female (data were not available for
      three patients), while 1, 4, 12 and 15 patients were, respectively, categorized
      as children, young adults, senior adults and elderly. Sources of Salmonella
      strains were urine (13), blood (11), purulent abscess (8), cerebrospinal fluid
      (3), peritoneal fluid, pleural fluid, wound exudates, aneurism (2 of each),
      ascitic fluid, sputum, tracheal aspirate, needle aspirate, bone and lymph node (1
      of each) samples. Only 28 Salmonella strains involved in FIs were available for
      further analysis. They were discriminated into 6 serotypes, and into 13 XbaI
      macrorestriction, 6 virulence, 11 antimicrobial resistance, 5 integron and 10
      plasmid profiles. Broadly, the pattern of serotype distribution of salmonellas
      involved in FIs matched that of those causing gastroenteritis, with the pandemic
      Enteritidis and Typhimurium (18 and 6 strains, respectively) being clearly
      predominant. Within serotype, the same lineages (as revealed by XbaI
      macrorestriction analysis as well as R- and V-profiles) were represented in both
      disease groups, with host-related factors apparently playing a more critical role
      than the individual strain in the outcome of the disease.

PMID- 16621700
TI  - Non-fatal sports and recreational violent injuries among children and teenagers,
      United States, 2001-2003.
AB  - BACKGROUND: An estimated 2.7 million non-fatal unintentional sports and
      recreational injuries are treated in U.S. hospital emergency departments (EDs)
      annually. However, little is known about the number of sports and recreational
      injuries resulting from violent behavior. METHODS: Data for 2001-2003 on sports
      and recreational injuries were obtained from the National Electronic Injury
      Surveillance System-All Injury Program (NEISS-AIP)-a national sample of 66 U.S.
      EDs. National estimates and rates of persons treated for violence-related sports
      and recreational injuries in EDs are compared to those treated for unintentional
      sports and recreational injuries. Types of injuries and injury circumstances are
      described. RESULTS: During the study period, an estimated 6,705 (8.3 per 100,000;
      95% confidence intervals (CI), 6.3-10.3) children and teenagers with violence
      related sports and recreational injuries were treated in U.S. EDs annually,
      compared to 2,698,634 children and teenagers with unintentional sports and
      recreational injuries. Thus, violent behavior accounted for 0.25% of sports and
      recreational injuries. The highest incidence rate (13.6 per 100,000) for violence
      related sports and recreational injuries was for children aged 10-14 years. Most
      patients with violence-related sports and recreational injuries were treated and
      released from the ED. A majority of those with violence-related sports and
      recreational injuries were injured to the head/neck region (52.2%), of which
      24.1% were treated for traumatic brain injuries. Most violent injuries resulted
      from being pushed or hit (65.6%); the most common sports and recreational
      activity varied by age: playground (65.2%) for children < or =9 years; bicycling
      (26.7%) for 10-14-year-olds; basketball (45.3%) for 15-19-year-olds. CONCLUSIONS:
      National ED surveillance systems can provide useful information pertaining to
      prevention programs designed to reduce sports and recreational injuries resulting
      from violent behavior and unintentional causes.

PMID- 16621701
TI  - The physical inactivity matrix: lessons from the classification of physical
      inactivity interventions.
AB  - Physical inactivity (PI), a leading modifiable cause of disease and injury, is
      endemic in industrialised nations. Although considerable research has been
      undertaken in this field, we lack a system to synthesise the research literature
      to inform policy and identify research needs. The aims of this study were to (1)
      develop a system to classify physical inactivity intervention studies, (2)
      examine the distribution of PI interventions published in the peer-reviewed
      health literature using the system, and (3) consider implications for future
      research. We developed the Physical Inactivity Matrix (PIM), with 12 intervention
      points, created by the intersection of two dimensions: the intervention target
      (individual, physical environment and social/cultural environment) and the
      activity focus (transport, work/school, leisure and consumer). A formal search of
      the health research literature identified 529 eligible studies and each was
      classified into one of the 12 cells of the PIM. Most studies were categorised as:
      individual-leisure (68%), individual-work/school (12%) or social/cultural
      environment-leisure (13%). Only 4% targeted the physical environment. The
      findings of this initial application of the PIM support the call for greater
      investment in policies, interventions and research that focus on the relationship
      between the environment and PI, and transportation in particular. There would be
      merit in establishing the inter-rater reliability of the PIM and applying it to a
      wider variety of studies, including those published in the transportation and
      urban planning literatures. The PIM could be a useful tool for monitoring trends
      in research directions and funding levels over time and across countries.

PMID- 16621702
TI  - Assessment of player performance following return to sport after hamstring muscle
      strain injury.
AB  - OBJECTIVE: To determine if there is any decrease in playing performance of
      athletes following return to sport after recovery from hamstring muscle strain
      injury. DESIGN: Prospective cohort study. PARTICIPANTS: One professional
      Australian football team over two playing seasons. METHODS: For every game, the
      team coach rated player performance proportional to time spent on the ground
      playing (an integer score out of a maximum of 10). Player performance ratings
      were compared pre- and post-hamstring muscle strain injury to assess player
      performance upon return to sport. RESULTS: Thirteen athletes had hamstring
      injuries and the required player ratings were available. The mean player
      performance rating for the entire playing season in which the player was injured
      was 6.9. The mean player performance rating for the two games prior to injury was
      6.8 as opposed to 5.4 for the two games after return to sport. Athletes had a
      significantly lower player performance rating immediately upon return to sport
      when compared to ratings for the entire season (p<0.001) and when compared to
      ratings from the two games prior to injury (p<0.001). CONCLUSIONS: Following
      return to sport from hamstring injury, player performance as assessed by the team
      coach is reduced. This suggests that some athletes may return to sport prior to
      complete resolution of the injury.

PMID- 16621703
TI  - Foot rotation--a potential target to modify the knee adduction moment.
AB  - Isolating the particular joints/limb segments associated with knee adductor
      moment variability may provide clinically important data that could help to
      identify strategies to reduce medial tibiofemoral joint load. The aim of this
      study was to examine whether or not foot and thigh rotation during human
      locomotion are significant determinants of knee adductor moment variability.
      Three-dimensional gait analyses were performed on 32 healthy adult women (mean
      age 54+/-12 years, mean BMI 25+/-4 kg m(-2)) with radiologically normal knees.
      The relationships between foot rotation, thigh rotation and the external knee
      adduction moment were examined during early and late-stance phases of the gait
      cycle. The degree of foot rotation correlated significantly with the magnitude of
      the peak knee adduction moment during late stance (r=0.40, p=0.024). No
      significant associations were apparent between thigh rotation and the peak knee
      adduction moment. The association between foot rotation and the knee adduction
      moment in this study suggests that women who walk with external rotation at the
      foot reduce their knee adduction moment during late stance. This result implies
      that changes in foot kinematics can modify the medial tibiofemoral load during
      gait, which may be important in the prevention and management of knee
      osteoarthritis.

PMID- 16621705
TI  - A question of precision.

PMID- 16621707
TI  - Quality of original medical papers.

PMID- 16621708
TI  - A complex fracture of the talus following a rugby union line-out.
AB  - Fractures of the talus are frequently difficult to treat. The vulnerable blood
      supply and abundant articular surfaces may lead to long-term problems with
      avascular necrosis and osteoarthritis. A case of a complex injury to the talus
      occurring in a rugby union player during a line-out is presented. The laws
      relating to line-out play disallow "lifting" and "levering" in the line out, but
      in reality allow "supporting" of the jumper on his shorts, once he has jumped. A
      further law insists on "lowering" of the supported jumper to the ground as soon
      as the ball has been won. This unusual injury to the talus clearly demonstrates
      the potential dangers of the line-out and the necessity that the laws of the game
      must be strictly adhered to, in order to ensure the safety of the line-out
      jumper.

PMID- 16621709
TI  - Effect of an integrated functional stability program on injury rates in an
      international netball squad.
AB  - The cost-effectiveness and efficacy of athlete profiling and injury prevention
      programs is influenced by procedural specificity, philosophy of athlete
      development within the sporting body and the dynamics within the
      multidisciplinary team (MDT). This article reports on the implementation of a
      multidisciplinary approach to injury reduction and performance development in an
      international netball squad. Problems with player compliance, training anxiety
      and injury rates sparked a decision to seek an alternative training approach. A
      reactive sports medicine system, poor player self-responsibility and inadequate
      player understanding of the anatomy and biomechanics of sound training,
      inadequate screening procedures and perceived conflict between sports science and
      sports medicine personnel were identified as causative factors. A new program was
      designed where common objectives were identified, and individual roles
      delineated. A functional profiling session was performed as a team activity and
      comprised player self-evaluation and netball specific movement analysis.
      Mechanisms of injury, training anxieties and modification of the overall program
      to ensure continued progression rather than a false plateau were illustrated
      through this process. From the above findings a strategy was outlined and
      comprised a foundation programme, a transitional phase, specific prophylactic
      programs, and sport specific sessions. A consistent approach was formulated
      across all disciplines in order to maximise transference of the new training
      program (TP). Training compliance was increased and interdisciplinary conflict
      prevented when dealing with different levels of training tolerance. Rate of
      injury in all vulnerable areas was markedly reduced. No training or overuse
      related injuries were sustained. Addressing fundamental functional problems and
      working openly and cooperatively towards a common goal, the members of the MDT
      were able to prevent injury, make significant gains in physiological performance
      and improve players' confidence and commitment to training over the defined
      period.

PMID- 16621710
TI  - The combined effects of hydration and exercise heat stress on choice reaction
      time.
AB  - The purpose of this investigation was to examine the combined effects of
      hydration and exercise heat stress on choice reaction time. On three separate
      occasions eight male subjects performed cycle exercise at approximately 70% of
      peak power output in warm, humid conditions (31 degrees C, 63% relative humidity)
      for a maximum of 90 min or until exhaustion. Throughout the trials, subjects
      ingested either a volume of water equal to fluid loss (100-FR), a volume
      equivalent to approximately 50% of fluid loss (50-FR), or no fluid (0-FR). A
      choice reaction time task was undertaken at rest, after 20 min of cycling, 40 min
      of cycling and at the conclusion of exercise. Mean reaction time for 100-FR was
      342.2+/-8.2 ms, 352.4+/-7.5 ms for 50-FR and 345.6+/-8.4 ms for 0-FR and were not
      significantly different. Choice reaction time was facilitated as the duration of
      exercise progressed with reaction time at 40 min and conclusion stages of
      exercise faster than at rest (P<0.005). Choice reaction time and accuracy were
      affected by the number of choices, with choice reaction time increasing linearly
      with the number of choices (P<0.005) and rate of incorrect responses increasing
      in the 4-choice task compared to the 1-choice and 2-choice task (P<0.05). The
      results indicate that, in up to 90 min of exercise in warm, humid conditions,
      choice reaction time is not compromised by different levels of hydration.

PMID- 16621711
TI  - Changes in athlete burnout over a thirty-week "rugby year".
AB  - Controversy over a negative experiential state among players, discussed as
      "burnout" in media reports, stimulated the New Zealand Rugby Union to commission
      research (including the present study) into players' experiences. Athlete burnout
      research to date has largely been limited to studies featuring cross-sectional
      designs. The purpose of this study was to examine changes in the key
      characteristics of burnout over a "rugby year", a 30-week competitive period
      involving two or more independent competitions. Players completed the Athlete
      Burnout Questionnaire at three different times during the 30-week competitive
      rugby year. Some statistically significant changes were observed in key
      characteristics of burnout across the competitive rugby year. Specifically
      players reported that their feelings of reduced accomplishment increased pre
      competition to in-competition phases. Changes in exhaustion over time were
      associated with playing position. Burnout was also associated with injury, non
      selection, rugby experience and team membership. Overall the results reflect that
      burnout is a dynamic experience and indicate that factors such as playing
      position, injury, selection and starting status are worthy of further
      investigation.

PMID- 16621712
TI  - Incidence and risk factors for injury in non-elite netball.
AB  - This paper identifies the risk and protective factors for injury in non-elite
      netball. Three-hundred and sixty-eight non-elite netballers completed a baseline
      questionnaire at the commencement of the 1997 preseason. Participants were
      telephoned each month during the 1997 and 1998 playing seasons to provide details
      of their exposure at training and games and any injury experiences in the
      previous 4 weeks. The incidence of injury in this study was 14 injuries per 1000
      player hours. The risk factors for injury were identified as: not warming up
      before a game (IRR 1.11, 95% CI 1.00-1.23) and not being open to new ideas (IRR
      1.04, 95% CI 1.00-1.07). Training for 4 or more hours per week (IRR 0.66, 95% CI
      0.45-0.98) and not sustaining an injury in the previous 12 months (IRR 0.58, 95%
      CI 0.43-0.79) were found to be protective against injury. The risk and protective
      factors for injury identified in this study can be used as the basis for the
      development of evidence-based injury prevention strategies that seek to reduce
      the risk of injury in sport. Injury prevention strategies should focus on the
      development of effective training programs that include netball-specific skills,
      activities and movements. Further investigation into the mechanisms associated
      with the risk and protective factors identified would provide further
      understanding of why these factors increase or decrease the risk of injury.

PMID- 16621715
TI  - Congenital left ventricular diverticulum.
AB  - Cardiac diverticula are rare and may have a wide spectrum of presentation ranging
      from an acute rupture and life threatening arrhythmias to being completely
      asymptomatic. The treatment options may vary but in view of their life
      threatening potential, the consensus is towards treating them early when the
      diagnosis was made. We present a case of an infant who presented in an emergency
      with cardiac arrest and was ultimately treated successfully on cardiopulmonary
      bypass and made an uneventful recovery. The literature has also been discussed on
      left ventricular diverticulum.

PMID- 16621716
TI  - TRAF3: a new component of the TLR-signaling apparatus.
AB  - Toll-like receptors (TLRs) are key sensors of microbially derived molecules that,
      upon activation, provide a pathogen-specific inflammatory response, leading to an
      efficient eradication of microbial pathogens. An important question has been how
      TLRs can provide signaling diversity when challenged with genotypic and
      functionally distinct pathogens. Recently, two studies have shown that tumor
      necrosis factor receptor-associated factor 3 (TRAF3) is an essential component of
      the TLR-signaling pathway, being a crucial regulator in the induction of TLR
      specific inflammatory responses.

PMID- 16621717
TI  - Gene-based vaccines: recent technical and clinical advances.
AB  - DNA vaccines have been widely used in efforts to develop vaccines against various
      pathogens as well as for cancer, autoimmune diseases and allergy. DNA vaccines
      offer broad efficacy (particularly for their ability to generate both cellular
      and humoral immunity), ease of construction and manufacture and the potential for
      world-wide usage even in low-resource settings. However, despite their successful
      application in many preclinical disease models, their potency in human clinical
      trials has been insufficient to provide protective immunity. Nevertheless, two
      DNA vaccines were recently licensed for use in animals (horse and fish),
      underscoring the potential of this technology. Here, we describe recent advances
      in increasing the potency of these vaccines, in understanding their immunological
      mechanisms, and in their applications and efficacy in clinical trials so far.

PMID- 16621718
TI  - Prominent crista terminalis and Eustachian ridge in the right atrium: Two
      dimensional (2D) and three dimensional (3D) imaging.
AB  - The crista terminalis and Eustachian ridge are normal anatomical structures
      within the right atrium that are not normally looked for or visualised in the
      standard views obtained while performing a transthoracic echocardiogram (TTE). In
      this case report, the prominent terminal ridge (a normal anatomical variant)
      appeared as a "mass" in the right atrium that needed to be differentiated from a
      pathological cardiac mass. Identification of physiological structures in the
      right atrium on TTE using additional 3D imaging can avoid unnecessary additional
      tests that are both more invasive and expensive such as transesophageal
      echocardiography or MRIs.

PMID- 16621719
TI  - Pulmonary atresia and ventricular septal defect with MAPCAs associated with right
      sided endocarditis and paradoxical embolic event.
AB  - Pulmonary atresia and ventricular septal defect (PA-VSD) with major
      aortopulmonary collaterals (MAPCAs) is a complex and extremely heterogeneous
      anomaly. PA-VSD with both pulmonary arteries originating from systemic arterial
      circulation without MAPCAs and patent ductus arteriosus (PDA) is a very rare
      disease and according to our knowledge a case without cyanosis and symptoms of
      congestive heart failure after the first decade of life has not been reported.
      The majority of untreated patients die in their first decade of life as a result
      of intractable congestive heart failure or respiratory distress. This report
      informs about a 21-year-old PA-VSD patient who presented without cyanosis with
      both pulmonary arteries arising from aorta associated with right sided
      endocarditis and a paradoxical embolic event.

PMID- 16621720
TI  - Clinical features of mixed physiology of constriction and restriction:
      echocardiographic characteristics and clinical outcome.
AB  - AIMS: An entity of patients with mixed physiology of constriction and restriction
      has been reported, however, the characteristics of these patients have not been
      well documented. We evaluated the clinical features and the outcome of these
      patients. METHODS AND RESULTS: Study subjects consisted of 38 patients (57+/-14
      years, 8 females, 30 males) who were diagnosed as having mixed physiology based
      on transthoracic and/or transesophageal echocardiography, MRI (or CT), cardiac
      catheterization, endomyocardial biopsy and/or surgical findings. Prior radiation
      therapy was the most frequent (50%) cause of mixed physiology followed by
      coronary artery bypass graft without prior radiation (24%) and heart
      transplantation (8%). The respiratory variation of peak early diastolic
      transmitral flow velocity by pulsed Doppler transesophageal echocardiography was
      10.7% in patients with sinus rhythm and 18.1% in patients with atrial arrhythmia.
      Pericardial thickening was noted adjacent to the right-sided chambers in 19
      patients, left-sided chambers in 10 patients, or both in 9 patients. All-cause 5
      year mortality was 40% and unrelated to age, etiology, left ventricular systolic
      function and therapeutic course. There was a statistically significant difference
      (p<0.01) between the survival rates in patients with mixed physiology and in
      patients with pure constriction (n=125). CONCLUSIONS: Due to the high mortality
      in this disease, discrimination of the entity from the patients with pure
      constriction is mandatory. Transthoracic and transesophageal echocardiography are
      helpful noninvasive techniques in the diagnosis and the understanding of the
      physiology of patients with mixed constriction and restriction.

PMID- 16621721
TI  - Geometric predictor of significant mitral regurgitation in patients with severe
      ischemic cardiomyopathy, undergoing Dor procedure: a real-time 3D
      echocardiographic study.
AB  - BACKGROUND AND PURPOSE: Significant mitral regurgitation (MR) is frequently
      associated with coronary artery disease. The precise geometric predictors of
      significant MR in ischemic cardiomyopathy are not clearly defined. We performed
      real-time 3D echocardiography (RT3DE) in 48 patients scheduled for infarct
      exclusion surgery or Dor procedure, 22 of whom had moderate or severe MR (DorMR)
      and 26 with no or trivial MR (DorNoMR). METHODS: Two orthogonal apical volumetric
      planes of LV, commissure-commissure (CC) and antero-posterior (AP) planes, were
      generated during mid-systole. Mitral valve tenting height (MVTht) and area (MVTa)
      were measured. The degree of leaflet tethering was estimated by the angles
      between the annular plane and each leaflet (anterior leaflet: Aalpha, posterior
      leaflet: Palpha). RESULTS: MVTht (1.11+/-0.14 vs 0.78+/-0.20 cm, P<0.01) and MVTa
      (1.30+/-0.34 vs 0.87+/-0.27 cm(2), P<0.01) were significantly larger in DorMR
      compared with DorNoMR. In DorMR, both Aalpha (38+/-6 vs 31+/-7 degrees , P<0.01)
      and Palpha (60+/-7 vs 41+/-8 degrees , P<0.01) significantly increased more than
      those in DorNoMR. Multiple logistic regression analysis found Palpha to be the
      most important geometric predictor of significant MR. MV tenting area was found
      to be the strongest determinant of MR severity in ischemic cardiomyopathy
      patients with significant MR by multivariate linear regression analysis.
      CONCLUSIONS: Detecting significant posterior leaflet tethering, the most
      important predictor of significant MR, and measuring MV tenting area, the
      strongest determinant of MR severity, using RT3DE may be helpful in decision
      making of additive surgical intervention for MR in patients with severe ischemic
      cardiomyopathy.

PMID- 16621722
TI  - Quality of life among people with epilepsy and mild intellectual disabilities in
      residential care.
AB  - This study examined quality-of-life (QOL) evaluations among people with epilepsy
      and mild intellectual disabilities in residential care to determine their
      covariation and potential determinants. Participants were 111 clients of the
      Bethel Institute, Bielefeld, Germany. They completed questionnaires on their
      overall QOL and life satisfaction, the PESOS scales on epilepsy-related QOL, the
      Brief Symptom Inventory (BSI), and scales on activities of daily life and work
      related problems in face-to-face-interviews. QOL evaluations differed in the
      various domains and tended to be better on more concrete items. Correlations of
      generic QOL parameters with scales on epilepsy-related QOL were only weak. BSI
      scores reflecting the current emotional state were identified as the most
      influential predictors of all QOL measures. The weak relationship between non
      health-related parameters of subjective QOL and epilepsy-related QOL requires
      further investigation and theoretical explanation, whereas the influence of
      negative affect on different QOL dimensions is in line with previous QOL
      findings.

PMID- 16621724
TI  - The evolutionary history and dynamics of bat rabies virus.
AB  - Rabies virus (RABV) is endemic in terrestrial mammals throughout the world and in
      bats on the American continent. We performed the most extensive phylogenetic
      analyses of bat RABV sequences undertaken to date using a variety of genes. Our
      study supported previous suggestions that viral sequences are grouped according
      to the behaviour of the host species. However, there was more genetic and
      geographical diversity within each phylogenetic group than previously recognised,
      including evidence for new groups. Furthermore, three clades of Latin American
      bat RABV that were distinct from the previously identified "group IV" bat RABV
      clade and more closely related to North American bat RABV clades, were
      identified. Strikingly, phylogenetic trees for the G (glycoprotein) gene had a
      significantly different evolutionary history to those inferred for the N
      (nucleoprotein) and P (phosphoprotein) genes, and an analysis of these competing
      topologies revealed that it is not possible on current data to resolve whether
      bat RABV arose from terrestrial mammal RABV, or vice-versa. Finally, using
      coalescent approaches, we estimated that RABV had similar rates of population
      growth and nucleotide substitution (approximately 2.5-4x10(-4) substitutions per
      site, per year) in both bats and terrestrial mammals, despite underlying
      differences in epidemiology.

PMID- 16621723
TI  - An agent- and ontology-based system for integrating public gene, protein, and
      disease databases.
AB  - In this paper, we describe OntoFusion, a database integration system. This system
      has been designed to provide unified access to multiple, heterogeneous biological
      and medical data sources that are publicly available over Internet. Many of these
      databases do not offer a direct connection, and inquiries must be made via Web
      forms, returning results as HTML pages. A special module in the OntoFusion system
      is needed to integrate these public 'Web-based' databases. Domain ontologies are
      used to do this and provide database mapping and unification. We have used the
      system to integrate seven significant and widely used public biomedical
      databases: OMIM, PubMed, Enzyme, Prosite and Prosite documentation, PDB, SNP, and
      InterPro. A case study is detailed in depth, showing system performance. We
      analyze the system's architecture and methods and discuss its use as a tool for
      biomedical researchers.

PMID- 16621725
TI  - Acquisition of antibodies to variant antigens on the surface of Plasmodium
      falciparum-infected erythrocytes during pregnancy.
AB  - Pregnancy-associated malaria is characterized by Plasmodium falciparum adherence
      to chondroitin sulfate A (CSA) in placenta, through a particular variant surface
      antigen (VSA). VSA(CSA)-specific IgG are involved in protection against placental
      malaria. In order to assess the relationship between VSA(CSA)-specific antibody
      responses and parity as well as protection against placental malaria, the
      occurrence of P. falciparum infection was assessed in 306 pregnant women from a
      low malaria transmission area of Senegal. Anti-VSA(CSA) antibodies against three
      placental parasite isolates were measured by flow cytometry, at enrollment and
      delivery. Placental infection prevalence rates were highest in primigravidae, but
      no clear decreasing trend was observed from the second pregnancy onwards. Anti
      VSA(CSA) antibody prevalence rates increased with parity. Both anti-VSA(CSA)
      antibody prevalence rates and levels increased during pregnancy only in women
      infected with P. falciparum. Although a single or a very limited number of P.
      falciparum infections were able to induce an anti-VSA(CSA) antibody response, the
      level or the quality of this response did not appear to confer protection against
      placental malaria infection.

PMID- 16621726
TI  - rpoB gene sequencing and spoligotyping of multidrug-resistant Mycobacterium
      tuberculosis isolates from India.
AB  - Multi drug-resistant Mycobacterium tuberculosis (MDR TB) has been well studied in
      outbreaks in settings of low endemicity in developed countries. However, the
      characteristics of MDR TB in the community with high endemicity such as India
      have not been well investigated. Mutations in the 81-bp rifampicin resistance
      determining region of the rpoB gene were analyzed by DNA sequencing of 187 M.
      tuberculosis clinical isolates (149 resistant and 38 sensitive) from different
      parts of India. 146-Point mutations and two insertions were found in 146 of 149
      resistant isolates in seven codons. The most common mutations were in codons 531
      (59%), 526 (22%), and 516 (11.5%). Mutations were not found in three (2%) of the
      resistant isolates. N-terminal sequencing in these isolates showed no mutation at
      codon V176. None of the drug-susceptible isolates showed any mutation in the 437
      bp rpoB gene segment sequenced. Genotypic analysis revealed a total of 80
      different spoligotypes. A unique pattern was found in 65 (43.6%) isolates,
      whereas 84 (56.4%) were in 15 clusters. Comparison with an international
      spoligotype database showed ST26, Delhi type (18.1%), ST1, Beijing type (9.4%),
      and ST11 (5.4%), as the most common. The majority of isolates in the Beijing
      genotype (13/14) were associated with mutation 531TTG and similar drug-resistance
      patterns while other major clusters showed that the nature and frequency of
      occurrence of mutations in the rpoB gene were independent of spoligopatterns.

PMID- 16621727
TI  - Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH
      kinase.
AB  - Disruption of the Saccharomyces cerevisiae mitochondrial NADH kinase POS5
      increases the mitochondrial mutation rate 50-fold. Whereas most multicellular
      eukaryotic genomes have one NADH kinase gene, the yeast genome contains three
      distinct genes encoding NAD/H kinase activity. To determine if all three genes
      are essential for viability we constructed combinations of gene knockouts. We
      show that only the pos5Deltautr1Delta combination is synthetically lethal,
      demonstrating an essential overlapping function, and showing that NAD/H kinase
      activity is essential for eukaryotic viability. The single human NAD/H kinase
      gene can rescue the lethality of the double knockout in yeast, demonstrating that
      the single human gene can fill the various functions provided by the three yeast
      genes. The human NAD/H kinase gene harbors very common sequence variants, but all
      of these equally complement the synthetic lethality in yeast, illustrating that
      each of these are functionally wild-type. To understand the molecular mechanism
      of the mitochondrial genome instability of pos5 mutation we performed gene
      expression analysis on the pos5Delta. The pos5Delta resulted in an increase in
      expression of most of the iron transport genes including key genes involved in
      iron-sulfur cluster assembly. Decreased expression occurred in many genes
      involved in the electron transport chain. We show that the pos5Delta expression
      pattern is similar to the frataxin homolog knockout (yfh1Delta), the yeast model
      for Friedreich's ataxia. These combined data show that the POS5 NAD/H kinase is
      an important protein required for a variety of essential cellular pathways and
      that deficient iron-sulfur cluster assembly may play a critical role in the
      mitochondrial mutator phenotype observed in the pos5Delta.

PMID- 16621729
TI  - Gene paucity, genome instability, clonal development: has an individual genome
      the potential to encode for more than one brain?

PMID- 16621730
TI  - A quest to understand molecular mechanisms for genetic stability.
AB  - In the midst of the post-war turmoil in Japan, I fortunately followed a path to
      become a scientist. Sometime at an early stage of my career, I encountered the
      problem of the cellular response to DNA damage and had the chance to discover a
      DNA repair enzyme. This event greatly influenced the subsequent course of my
      research, and I extended my studies toward elucidating the molecular mechanisms
      of mutagenesis as well as of carcinogenesis. Through these studies I came to
      understand the importance of mechanisms for dealing with the actions of reactive
      oxygen species to the living systems. These recollections deal with these
      endeavors with emphasis on the early part of my scientific career.

PMID- 16621731
TI  - MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and
      neurotoxicity of oxidized purine nucleotides.
AB  - In human and rodent cells, MTH1, an oxidized purine nucleoside triphosphatase,
      efficiently hydrolyzes oxidized dGTP, GTP, dATP and ATP such as 2'-deoxy-8
      oxoguanosine triphosphate (8-oxo-dGTP) and 2'-deoxy-2-hydroxyadenosine
      triphosphate (2-OH-dATP) in nucleotide pools, thus avoiding their incorporation
      into DNA or RNA. MTH1 is expressed in postmitotic neurons as well as in
      proliferative tissues, and it is localized both in the mitochondria and nucleus,
      thus suggesting that MTH1 plays an important role in the prevention of the
      mutagenicity and cytotoxicity of such oxidized purines as 8-oxoG which are known
      to accumulate in the cellular genome. Our recent studies with MTH1-deficient mice
      or cells revealed that MTH1 efficiently minimizes accumulation of 8-oxoG in both
      nuclear and mitochondrial DNA in the mouse brain as well as in cultured cells,
      thus contributing to the protection of the brain from oxidative stress.

PMID- 16621732
TI  - Tetratricopeptide-motif-mediated interaction of FANCG with recombination proteins
      XRCC3 and BRCA2.
AB  - Fanconi anaemia is an inherited chromosomal instability disorder characterised by
      cellular sensitivity to DNA interstrand crosslinkers, bone-marrow failure and a
      high risk of cancer. Eleven FA genes have been identified, one of which, FANCD1,
      is the breast cancer susceptibility gene BRCA2. At least eight FA proteins form a
      nuclear core complex required for monoubiquitination of FANCD2. The BRCA2/FANCD1
      protein is connected to the FA pathway by interactions with the FANCG and FANCD2
      proteins, both of which co-localise with the RAD51 recombinase, which is
      regulated by BRCA2. These connections raise the question of whether any of the
      FANC proteins of the core complex might also participate in other complexes
      involved in homologous recombination repair. We therefore tested known FA
      proteins for direct interaction with RAD51 and its paralogs XRCC2 and XRCC3.
      FANCG was found to interact with XRCC3, and this interaction was disrupted by the
      FA-G patient derived mutation L71P. FANCG was co-immunoprecipitated with both
      XRCC3 and BRCA2 from extracts of human and hamster cells. The FANCG-XRCC3 and
      FANCG-BRCA2 interactions did not require the presence of other FA proteins from
      the core complex, suggesting that FANCG also participates in a DNA repair complex
      that is downstream and independent of FANCD2 monoubiquitination. Additionally,
      XRCC3 and BRCA2 proteins co-precipitate in both human and hamster cells and this
      interaction requires FANCG. The FANCG protein contains multiple tetratricopeptide
      repeat motifs (TPRs), which function as scaffolds to mediate protein-protein
      interactions. Mutation of one or more of these motifs disrupted all of the known
      interactions of FANCG. We propose that FANCG, in addition to stabilising the FA
      core complex, may have a role in building multiprotein complexes that facilitate
      homologous recombination repair.

PMID- 16621733
TI  - Non-invasive forced expiratory flow-volume curves to measure lung function in
      cats.
AB  - Forced expiratory flow-volume curves were performed in 15 cats using the non
      invasive thoracic compression techniques developed for use in human infants. Cats
      breathed through a face mask and pneumotachygraph from which flow and volume were
      obtained. Thoracic compression was applied from an inflatable bag in a non
      expandable jacket surrounding the animal. Bag inflation at end inspiration was
      initiated by a computer pulse to a pressurized chamber. Processed signals from
      the pneumotachygraph determined maximum-forced expiratory flow at lung volume
      equivalent to functional residual capacity (FRC), termed V'maxFRC. Different
      compression pressures were used, and the highest value from a technically
      satisfactory flow-volume loop was taken as the result. Mean (+/- 95% CI) V'maxFRC
      was 422 (369-475) ml/s. Compared with infants of similar weight (V'maxFRC
      approximately 180 ml/s), cats had a much higher V'maxFRC. Tests repeated another
      day showed a mean (+/-95% CI) percentage difference between paired tests to be
      2.8 (-12.6, +18.3)%. Non-invasive forced expiratory flow-volume measurements can
      be reliably obtained in sedated cats.

PMID- 16621734
TI  - Adaptive responses of vertebrate neurons to anoxia--matching supply to demand.
AB  - Oxygen depleted environments are relatively common on earth and represent both a
      challenge and an opportunity to organisms that survive there. A commonly observed
      survival strategy to this kind of stress is a lowering of metabolic rate or
      metabolic depression. Whether metabolic rate is at a normal or a depressed level
      the supply of ATP (glycolysis and oxidative phosphorylation) must match the
      cellular demand for ATP (protein synthesis and ion pumping), a condition that
      must of course be met for long-term survival in hypoxic and anoxic environments.
      Underlying a decrease in metabolic rate is a corresponding decrease in both ATP
      supply and ATP demand pathways setting a new lower level for ATP turnover. Both
      sides of this equation can be actively regulated by second messenger pathways but
      it is less clear if they are regulated differentially or even sequentially with
      the onset of anoxia. The vertebrate brain is extremely sensitive to low oxygen
      levels yet some species can survive in oxygen depleted environments for extended
      periods and offer a working model of brain survival without oxygen. Hypoxia
      tolerant vertebrate brain will be the primary focus of this review; however, we
      will draw upon research involving hypoxia/ischemia tolerance mechanisms in liver
      and heart to offer clues to how brain can tolerate anoxia. The issue of
      regulating ATP supply or demand pathways will also be addressed with a focus on
      ion channel arrest being a significant mechanism to reduce ATP demand and
      therefore metabolic rate. Furthermore, mitochondria are ideally situated to serve
      as cellular oxygen sensors and mediator of protective mechanisms such as ion
      channel arrest. Therefore, we will also describe a mitochondria based mechanism
      of ion channel arrest involving ATP-sensitive mitochondrial K(+) channels,
      cytosolic calcium and reaction oxygen species concentrations.

PMID- 16621735
TI  - Supramedullary influences on cough.
AB  - The evidence for supramedullary influences on cough is largely indirect. Cough
      can be voluntarily induced or inhibited, functions usually thought to reside in
      the cerebral cortex. A sensation of 'urge-to-cough' usually precedes cough due to
      an airway irritant stimulus, and this may well involve the cerebral cortex. In
      conditions with interruption of the pathways between the cortex and the
      brainstem, such as strokes and Parkinson's disease, voluntary cough may be
      inhibited without disruption of reflex cough from the larynx or lower airways.
      'Habit cough', like Tourette's syndrome, is assumed to be cortically mediated.
      Placebos and many treatments based on complementary medicine are effective in
      inhibiting clinical cough, and the site of action is likely to be the cerebral
      cortex. In sleep and in anaesthesia cough is depressed and, again, this seems
      likely to be at a cortical level. However there are few or no experimental or
      clinical observation as to the localization and functions of supramedullary areas
      responsible for cough. It is a field of research wide open for exploration.

PMID- 16621736
TI  - Effects of femoral vascular occlusion on ventilatory responses during recovery
      from exercise in human.
AB  - We investigated the effect of occluding of femoral blood flow on the post
      exercise ventilatory response of both the sub- and supra-anaerobic threshold (AT)
      leg cycling in humans. Seven healthy subjects (aged 21-44 years) volunteered to
      participate in this study. The protocol consisted of 6 min constant-load upright
      cycling at either a sub-AT (80% of AT) or supra-AT (midway between AT and
      VO(2)max) work rate and a subsequent 6 min rest period either with or without
      femoral blood flow being occluded by a rapid cuff inflation to 250 Torr during
      the first 2 min of recovery. Blood lactate levels at the cessation of the sub-
      and supra-AT exercise averaged 1.8+/-0.2 and 4.9+/-0.4 mequiv.l(-1) (mean+/
      S.E.M.), respectively. Compared to spontaneous recovery, the circulatory
      occlusion significantly reduced ventilation irrespective of the intensity of the
      preceding exercise. The relative contribution of the ventilatory deficit to the
      total spontaneous ventilation (defined as the difference between the cumulative
      ventilation with and without cuff inflation during the first 2 min of recovery)
      was significantly greater supra-AT (18.0+/-3.9%) than sub-AT (9.3+/-2.9%,
      P<0.05). The subsequent release of occlusion was accompanied by a rapid increase
      in ventilation that began on the first breath after release. We concluded that
      the relatively greater speeding of ventilatory decline with occlusion during the
      first 2 min of recovery from supra-AT exercise argues against a significant role
      for an intramuscular chemoreflex-induced hyperpnoea. Rather, mechanisms related
      to the hemodynamic effects of suddenly altered muscle perfusion seem more
      consistent with this phenomenon.

PMID- 16621737
TI  - Development of an HPLC method for the determination of nifedipine in human plasma
      by solid-phase extraction.
AB  - Nifedipine, a dihydropyridine calcium channel antagonist, is widely used in the
      treatment of hypertension and other cardiovascular disorders. A selective,
      sensitive and accurate high-performance liquid chromatographic method has been
      developed, validated and applied for determination of nifedipine in human plasma
      samples. A series of studies were conducted in order to investigate the effects
      of mobile phase composition, buffer concentration, mobile phase pH and
      concentration of organic modifiers, and to develop a convenient and easy-to-use
      method for quantitative analysis of nifedipine. The method involves solid-phase
      extraction on C18 cartridges. The chromatographic separation was accomplished on
      a Lichrocart Lichrospher 60 RP selectB column with a mobile phase composed of
      0.020 mol/L KH2PO4 (pH 4.8) and acetonitrile (42:58, v/v). UV detection was set
      at 240 nm. The calibration curve was linear in the concentration range of 5.0
      200.0 ng/mL for nifedipine in plasma and the limit of quantification was 5.0
      ng/mL.

PMID- 16621738
TI  - Analysis of glutathione and glutathione disulfide in human saliva using
      hydrophilic interaction chromatography with mass spectrometry.
AB  - A sensitive method for the determination of glutathione (GSH) and glutathione
      disulfide (GSSG) in human saliva was developed and validated. GSH was captured
      and stabilized by the addition of N-ethylmaleimide (NEM). Solid-phase extraction
      (SPE) using an Oasis MAX extraction cartridge was employed for sample preparation
      and analysis was performed on a Shimadzu LCMS-2010 A that was operated in the
      single ion monitoring mode using positive ion electrospray ionization (ESI) as
      the interface. The monitored ion for GSH-NEM was m/z 433 and that for GSSG was
      m/z 613. Chromatography was carried out on an Atlantis HILIC silica column (150
      mm x 2.1 mm, 5 microm) with acetonitrile and formate buffer as the mobile phase
      at the flow rate of 0.2 ml/min. The calibration curve was linear over the range
      of 0.1-100 microM for GSH-NEM. The extraction recoveries of GSH-NEM spiked at
      concentrations of 25 and 50 microM were 97.1 and 104.4%, respectively. Similar
      results were obtained for GSSG. The newly developed hydrophilic interaction
      chromatography with mass spectrometry (HILIC/MS) method showed superior
      sensitivity for the determination of GSH and GSSG in human saliva samples.

PMID- 16621739
TI  - High sensitive determination of sufentanil in human plasma of parturients and
      neonates following patient-controlled epidural analgesia (PCEA).
AB  - A validated method for the determination of sufentanil in human plasma using
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) is described.
      Sufentanil was extracted from human plasma with solid-phase-extraction using
      deuterated sufentanil, [(2)H(5)]-sufentanil, as internal standard. Sufentanil and
      the internal standard were determined with an API 4000 tandem mass spectrometer
      equipped with a Turbo-V-Source operating in positive ESI mode on an Alltima HP
      HILIC straight phase column. The method showed a lower limit of quantification of
      0.25 pg/ml (12.5 fg on column). The applicability of the method is shown in a
      clinical study, in which levels of sufentanil in plasma of parturients and
      arterial umbilical plasma of their neonates following patient-controlled epidural
      analgesia (PCEA) under several regimen treatments was analyzed.

PMID- 16621740
TI  - Resolution of common dietary sugars from probe sugars for test of intestinal
      permeability using capillary column gas chromatography.
AB  - BACKGROUND: The most widely accepted method for the evaluation of intestinal
      barrier integrity is the measurement of the permeation of sugar probes following
      an oral test dose of sugars. The most-widely used sugar probes are sucrose,
      lactulose, mannitol and sucralose. Measuring these sugars using a sensitive gas
      chromatographic (GC) method, we noticed interference on the area of the lactulose
      and mannitol peaks. METHODS: We tested different sugars to detect the possible
      makeup of these interferences and finally detected that the lactose interferes
      with lactulose peak and fructose interferes with mannitol peak. On further
      developing of our method, we were able to reasonably separate these peaks using
      different columns and condition for our assay. Sample preparation was rapid and
      simple and included adding internal standard sugars, derivitization and
      silylation. We used two chromatographic methods. In the first method we used
      Megabore column and had a run time of 34 min. This resulted in partial separation
      of the peaks. In the second method we used thin capillary column and was able to
      reasonably separate the lactose and lactulose peaks and the mannitol and fructose
      peaks with run time of 22 min. RESULTS: The sugar probes including mannitol,
      sucrose, lactulose, sucralose, fructose and lactose were detected precisely,
      without interference. The assay was linear between lactulose concentrations of
      0.5 and 40 g/L (r(2)=1.000, P<0.0001) and mannitol concentrations of 0.01 and 40
      g/L (r(2)=1.000). The sensitivity of this method remained high using new column
      and assay condition. The minimum detectable concentration calculated for both
      methods was 0.5 mg/L for lactulose and 1 mg/L for mannitol. CONCLUSION: This is
      the first report of interference of commonly used sugars with test of intestinal
      permeability. These sugars are found in most of fruits and dairy products and
      could easily interfere with the result of permeability tests. Our new GC assay of
      urine sugar probes permits the simultaneous quantitation of sucralose, sucrose,
      mannitol and lactulose, without interference with lactose and fructose. This
      assay is a rapid, simple, sensitive and reproducible method to accurately measure
      intestinal permeability.

PMID- 16621741
TI  - Direct determination of verapamil in urine and serum samples by micellar liquid
      chromatography and fluorescence detection.
AB  - Verapamil, a calcium channel antagonist, is one of the most commonly prescribed
      drugs in the treatment of hypertension. In this work, it was determined in serum
      and urine samples by a sensitive and precise chromatographic procedure without
      any pre-treatment step in a C18 column using a micellar mobile phase of 0.15M
      sodium dodecyl sulfate and 5% pentanol at pH 7. Fluorescence detection set at 230
      nm (excitation) and 312 nm (emission) was used. Verapamil is eluted at 12.5 min
      with no interference by the protein band or endogenous compounds. Linearities (r
      > 0.998), as well as intra- and inter-day precision, were studied in the
      validation of the method. LODs were also calculated to be 11.0, 18.5 and 20.2
      ng/mL in micellar solution, serum and urine, respectively. Recoveries in the
      biological matrices were in the 97-99% range. Drug excretion in urine was studied
      in a volunteer receiving treatment for hypertension, and verapamil, as an
      unchanged drug, was separated from other metabolites. The procedure developed can
      be useful in the field of toxicology and clinical analysis.

PMID- 16621742
TI  - Studies by biointeraction chromatography of binding by phenytoin metabolites to
      human serum albumin.
AB  - Biointeraction studies based on high performance affinity chromatography were
      used to investigate the binding of human serum albumin (HSA) to two major
      phenytoin metabolites: 5-(3-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) and 5-(4
      hydroxyphenyl)-5-phenylhydantoin (p-HPPH). This was initially examined by
      conducting self-competition zonal elution experiments in which m-HPPH or p-HPPH
      were placed in both the mobile phase and injected sample. It was found that each
      metabolite had a single major binding site on HSA. Competitive zonal elution
      experiments using l-tryptophan, warfarin, digitoxin, and cis-clomiphene as site
      selective probes indicated that m-HPPH and p-HPPH were interacting with the
      indole-benzodiazepine site of HSA. The estimated association equilibrium
      constants for m-HPPH and p-HPPH at this site were 3.2 (+/-1.2)x10(3) and 5.7 (+/
      0.7)x10(3)M(-1), respectively, at pH 7.4 and 37 degrees C. Use of these
      metabolites as competing agents for injections of phenytoin demonstrated that m
      HPPH and p-HPPH had direct competition with this drug at the indole
      benzodiazepine site. However, the use of phenytoin as a competing agent indicated
      that this drug had additional negative allosteric interactions on the binding of
      these metabolites to HSA. These results agreed with previous studies on the
      binding of phenytoin to HSA and its effects on the interactions of HSA with site
      selective probes for the indole-benzodiazepine site.

PMID- 16621743
TI  - Preparation of inorganic molecularly imprinted polymers with higher adsorption
      and selectivity by sol-gel method.
AB  - Preparation of inorganic molecularly imprinted polymers (IMIPs) with higher
      adsorption and selectivity has been developed on caffeine as model compound by
      sol-gel processes. In our study, by introducing pore-forming agent, lactic acid,
      into sol-gel process, the porosity of IMIPs was enhanced and the performance of
      IMIPs was thus improved. And, by introducing base catalyst in the sol-gel
      process, large pore volume was obtainable, and the caffeine adsorption of IMIPs
      was increased. Competition adsorption experiments between caffeine (CAF) and
      structure analogous molecule, theophylline (TH), were determined by HPLC
      analysis. It was found that adding pore-forming agent method produced better
      caffeine adsorption (ca. 20 micromol/g) than by adding base catalyst. But adding
      base catalyst method was found to yield better selectivity (ca. 4) (Selectivity
      (alpha) is the ratio of CAF bound to TH bound.) In addition, caffeine adsorption
      of IMIPs with template removed by calcination is two times that by extraction
      without sacrificing the selectivity of IMIPs.

PMID- 16621744
TI  - What's the case for case-finding in primary care for coeliac disease?

PMID- 16621745
TI  - Recurrent massive haemorrhage from an endoscopically inevident isolated rectal
      varix.
AB  - Anorectal varices are identified endoscopically in up to 40% of patients with
      liver cirrhosis [Misra SP, Dwivedi M, Misra V. Prevalence and factors influencing
      haemorrhoids, anorectal varices, and colopathy in patients with portal
      hypertension. Endoscopy 1996;28:340-5] but are an infrequent cause of bleeding
      and their management remains controversial. We present a patient with chronic
      hepatitis C virus infection who developed recurrent haemorrhage from an isolated,
      endoscopically inevident rectal varix in the absence of clinical or endoscopic
      evidence of portal hypertension. The difficulties in diagnosis and management of
      anorectal varices are highlighted.

PMID- 16621746
TI  - A new medical device to assist the introduction of ambulatory 24-h pH-metry
      probe.

PMID- 16621747
TI  - Pain perception development and maturation.
AB  - Newborn infants are not small adults. The pharmacokinetics and dynamics of
      analgesic drugs are immature at birth. Volumes of distribution, drug clearances,
      side-effects and drug efficacy all differ in newborns as compared to adults.
      Interestingly, these parameters develop before birth and during the postnatal
      period, reaching adult values after a period of months or years. This means that
      clinicians should anticipate on pharmacokinetic/pharmacodynamic (PK/PD) changes
      in newborns with increasing post-conceptual age. The ability to perceive pain
      might also be immature at birth. Lower pain thresholds due to the absence of
      inhibitory descending spinothalamic fibers and a not yet fully developed cortical
      pain memory system are points of interest for our understanding of differences in
      pain perception in the newborn infant. Although this is a relatively unexplored
      area of research in humans, we will discuss the maturation and development of
      neonatal pain experience and perception in this paper.

PMID- 16621748
TI  - Fetal pain perception and pain management.
AB  - This paper gives an overview of current science related to the concept of fetal
      pain. We have answered three important questions: (1) does fetal pain exist? (2)
      does management of fetal pain benefit the unborn child? and (3) which techniques
      are available to provide good fetal analgesia?

PMID- 16621749
TI  - Inflammatory responses in the placenta and umbilical cord.
AB  - Histopathological examination of the placenta is the gold standard for evaluating
      antenatal inflammatory processes that might influence fetal development.
      Histological chorioamnionitis develops through a well-characterised stereotyped
      progression of maternal and fetal cellular stages that vary from patient to
      patient and are amenable to quantification. Increases in the intensity of these
      responses and their gradual transformation into a chronic phase are important
      variables that can adversely affect fetal physiology. Under recognised placental
      inflammatory lesions affecting the decidua, placental villi and fetal vessels are
      also potentially informative factors that should be taken into account in the
      studies of adverse pregnancy outcomes. This review summarises the relationships
      between aetiology, intensity, duration, characteristics and site of histological
      placental inflammation and suggests how these data may help to better understand
      the antenatal environment.

PMID- 16621750
TI  - Pain control: opioid dosing, population kinetics and side-effects.
AB  - Neonates undergoing invasive procedures, postoperative pain or ventilatory
      support commonly receive opioids for treating pain and stress. Randomized
      clinical trials have examined the benefits and adverse effects of morphine or
      fentanyl for ventilated neonates and other indications. This paper summarizes the
      current evidence for opioid dosing in newborns, reviews their side-effects and
      explains the use of population kinetics and non-linear mixed-effects modeling to
      analyze the data from clinical trials. Opioid use should be reserved for severe
      pain postoperatively or during intensive care in neonates, using continuous
      infusions rather than intermittent boluses. The safety and efficacy data from
      prolonged opioid use, particularly on the long-term outcomes of neonates, is
      still lacking. The pharmacodynamics and pharmacogenetics of opioid use in infancy
      needs further investigation, using non-linear mixed-effects models to drive
      individualized therapy. The current interest in opioid research will reap rich
      dividends in providing pain relief for neonates and avoiding dangerous side
      effects.

PMID- 16621751
TI  - Capsaicin and gastric ulcers.
AB  - In recent years, infection of the stomach with the organism Helicobacter Pylori
      has been found to be the main cause of gastric ulcers, one of the common ailments
      afflicting humans. Excessive acid secretion in the stomach, reduction in gastric
      mucosal blood flow, constant intake of non-steroid anti-inflammatory drugs
      (NSAIDS), ethanol, smoking, stress etc. are also considered responsible for ulcer
      formation. The prevalent notion among sections of population in this country and
      perhaps in others is that "red pepper" popularly known as "Chilli," a common
      spice consumed in excessive amounts leads to "gastric ulcers" in view of its
      irritant and likely acid secreting nature. Persons with ulcers are advised either
      to limit or avoid its use. However, investigations carried out in recent years
      have revealed that chilli or its active principle "capsaicin" is not the cause
      for ulcer formation but a "benefactor." Capsaicin does not stimulate but inhibits
      acid secretion, stimulates alkali, mucus secretions and particularly gastric
      mucosal blood flow which help in prevention and healing of ulcers. Capsaicin acts
      by stimulating afferent neurons in the stomach and signals for protection against
      injury causing agents. Epidemiologic surveys in Singapore have shown that gastric
      ulcers are three times more common in the "Chinese" than among Malaysians and
      Indians who are in the habit of consuming more chillis. Ulcers are common among
      people who are in the habit of taking NSAIDS and are infected with the organism
      "Helicobacter Pylori," responsible for excessive acid secretion and erosion of
      the mucosal layer. Eradication of the bacteria by antibiotic treatment and
      avoiding the NSAIDS eliminates ulcers and restores normal acid secretion.

PMID- 16621752
TI  - Criteria for optimizing food composition tables in relation to studies of
      habitual food intakes.
AB  - The purpose of this study is to increase the accuracy, reliability, and precision
      of food composition data and, in consequence, better approximate nutrient intake
      estimations and recommendations. To do this it is necessary to specify and taken
      into account factors that play an important role in the variation of composition
      in order to avoid excessively broad dispersions and irregularities in data
      distributions. This implies the presentation of representative and, as
      consequence, extrapolable data, with nutritionally grounded confidence intervals.
      This study suggests a methodology that better approaches the accuracy,
      reliability, and precision of food composition data.

PMID- 16621753
TI  - Creating proteins with novel functionality via the Maillard reaction: a review.
AB  - Proteins are widely utilized to add functional properties, such as gelling and
      emulsification to foods. These attributes depend on a number of factors such as
      molecular structure of the protein, the pH, and the composition of its chemical
      environment. There is substantial evidence to suggest that the functional
      properties of food proteins can be further improved by derivatization. Covalent
      bonding of proteins to polysaccharides and smaller reducing sugars via the
      Maillard reaction has been shown to alter the functionality of proteins without
      requiring the addition of chemical reagents. Establishment of a technologically
      feasible method for preparing the conjugates and optimization of the processing
      conditions, however, is needed to promote their development as functional food
      ingredients. This paper provides a state-of-the-art contribution to the impact of
      the Maillard reaction on protein functionality. It presents a deeper
      understanding of the influence of processing conditions and reactant formulation
      on improving desirable properties of proteins. In particular attention is given
      to how potential improvements could be achieved in the emulsifying, textural, and
      solubility properties of proteins to add value to commodity food ingredients.
      Elements that are considered to be critical to the design of functional Maillard
      conjugates are highlighted and suggestions proposed to facilitate progress in
      this area.

PMID- 16621754
TI  - Functional improvement of milk whey proteins induced by high hydrostatic
      pressure.
AB  - High pressure is emerging as a new processing technology that produces particular
      changes in the molecular structure of proteins and thus gives rise to new
      properties inaccessible via conventional methods of protein modification. This
      review deals with the main effects of high hydrostatic pressure on the
      physicochemical characteristics of milk whey proteins and how modifications in
      their structural properties contribute to functionality. In this paper the
      mechanism underlying pressure-induced changes in ss-lactoglobulin, a-lactabumin,
      and bovine serum albumin is explained, and related to functional properties such
      as gel-forming ability, emulsifying activity, or foaming capacity. The
      possibility of using high pressures to favor chemical reactions of proteins with
      other food components, such as carbohydrates, to produce novel molecules with new
      food uses is also considered.

PMID- 16621755
TI  - Associations between milk performance traits in Holstein cows and 16 candidate
      SNPs identified by arrayed primer extension (APEX) microarray.
AB  - An oligonucleotide microarray-which allows for parallel genotyping of many SNPs
      in genes involved in cow milk protein biosynthesis-was used to identify which of
      the 16 candidate SNPs are associated with milk performance traits in Holstein
      cows. Four hundred cows were genotyped by the developed and validated microarray.
      Significant associations were found between four single SNPs, namely DGAT1
      (acyloCoA:diacylglycerol acyltransferase), LTF (lactoferrin), CSN3 (kappa
      casein), and GHR (growth hormone receptor) and with fat and protein yield and
      percentage. Many significant associations between combined genotypes (two SNPs)
      and milk performance traits were found. The associations between the combined
      genotypes DGAT1/LTF and DGAT1/LEPTIN analyzed traits are presented as examples.
      The microarray based on APEX (Arrayed Primer Extension) is a fast and reliable
      method for multiple SNP analysis of potential application in marker-assisted
      selection. After further development, the chip may prospectively be used for
      dairy cattle paternity analysis and evolutionary studies.

PMID- 16621756
TI  - Differential glycosylation of rhLf expressed in the mammary gland of transgenic
      mice.
AB  - Differential glycosylation of natural hLf and rhLf from hLf-transgenic mice,
      which harbored a 146 Kb BAC insert that includes the intact hLf gene sequence,
      was studied in the present report. There were significant differences between the
      immunoblotting results of rhLf and natural hLf, which were denatured with
      nonreducing SDS sample buffer. The differences disappeared after rhLf and natural
      hLf samples were digested with N-glycosidase F, respectively. The results showed
      that there were significant differences (P<0.01) between the glycosylation of
      natural hLf and rhLf that were purified, respectively, from milk samples of seven
      hLf-transgenic mouse lines.

PMID- 16621757
TI  - Global gene expression profiling of Bovine immature B cells using serial analysis
      of gene expression.
AB  - The Peyer's patches of the small intestine are important sites of antigen
      processing. The follicles of the Peyer's patches receive the antigen transported
      by the M cells at the mucosal surface and then play a major role in development
      of both protective humoral and mucosal immune responses. Serial analysis of gene
      expression (SAGE) was employed to derive the global gene expression profile of B
      lymphocytes isolated from the IPPF. Analysis of the SAGE data revealed the
      identity of genes and the level to which they are expressed by IPPF B
      lymphocytes. This analysis indicated that they were metabolically active and that
      the transcripts encoding proteins necessary for a response to antigen
      presentation were expressed. These transcripts included the B cell receptor
      components CD76a and b (Ig-alpha and Ig-beta) and accessory c-Src family kinases
      Lyn and Blk. Furthermore, many of the positive and negative regulators, and
      accessory proteins that are necessary for B cell antigen receptor signaling were
      identified. Also present were transcripts encoding interleukins and their cognate
      receptors. Overall, this SAGE analysis yielded a global picture of gene
      expression in IPPF B lymphocytes and provides a starting point for the comparison
      of gene expression in further functional studies.

PMID- 16621758
TI  - Polymorphisms within the lactoferrin gene promoter in various cattle breeds.
AB  - Lactoferrin (Lf) is an iron-binding protein and belongs to the serum transferrin
      family. It has broad spectrum antimicrobial action, and it is found in exocrine
      secretions including milk. The sequence of the bovine lactoferrin gene promoter
      was analyzed in five different cattle breeds (Holstein Friesian, New Zealand
      Holstein, Montebeliard, Normande, and Norwegian Red) to determine the extent of
      polymorphic variation, which exists in this region both within and across cattle
      breeds. Fifteen different single nucleotide polymorphisms (SNPs) were identified
      throughout this region. Numerous polymorphisms were found throughout the Holstein
      Friesian, New Zealand Holstein, Montebeliard, and Normande populations. The most
      frequently encountered polymorphism found in all breeds was at position -28,
      which is immediately proximal to the TATA box of the promoter. The most variable
      base position was -131, which included three types of heterozygotes including a
      single base deletion in one allele, and three homozygote variants. This
      polymorphism occurs in a putative transcription factor binding site, for the
      nuclear factor of activated T cells (NF-ATc). A unique polymorphism was
      identified in one Normande animal, and three polymorphisms were found in one
      Montebeliard animal. In general, Norwegian Red cattle displayed fewer SNPs than
      other breeds. Most nucleotide changes in these animals were within the 190 base
      pairs of the transcription start point, with the exception of an insertion seen
      in three animals at position -478. In conclusion, SNPs were found in abundance
      throughout this regulatory region. Whether or not these polymorphisms have an
      effect on the regulation of the bovine lactoferrin gene is yet to be elucidated.
      However, the identification of lactoferrin promoter variants may serve as a
      marker for healthier animals, thereby accelerating the improvement of animals
      through breeding.

PMID- 16621759
TI  - Establishment of immortal swine kidney epithelial cells.
AB  - Using normal swine kidney epithelial (SKE) cells that were shown to be senescent
      at passages 12 to 14, we have established one lifespan-extended cell line and two
      lifespan-extended cell lines by exogenous introduction of the human catalytic
      subunit of telomerase (hTERT) and simian virus 40 large T-antigen (SV40LT), all
      of which maintain epithelial morphology and express cytokeratin, a marker of
      epithelial cells. SV40LT- and hTERT-transduced immortal cell lines appeared to be
      smaller and exhibited more uniform morphology relative to primary and
      spontaneously immortalized SKE cells. We determined the in vitro lifespan of
      primary SKE cells using a standard 3T6 protocol. There were two steps of the
      proliferation barrier at 12 and 20, in which a majority of primary SKE cells
      appeared enlarged, flattened, vacuolated, and ss-galactosidase-positive, all
      phenotypical characteristics of senescent cells. Lifespan-extended SKE cells were
      eventually established from most of the cellular foci, which is indicative of
      spontaneous cellular conversion at passage 23. Beyond passage 25, the rate of
      population doubling of the established cells gradually increased. At passage 30,
      immortal cell lines grew faster than primary counterpart cells in 10% FBS-DMEM
      culture conditions, and only SV40LT-transduced immortal cells grew faster than
      primary and other SKE immortal cells in 0.5% FBS-DMEM. These lifespan-extended
      SKE cell lines failed to grow in an anchorage-independent manner in soft-agar
      dishes. Hence, three immortalized swine kidney epithelial cells that are not
      transformed would be valuable biological tools for virus propagation and basic
      kidney epithelial cell research.

PMID- 16621760
TI  - Interferon-alpha genes from Bos and Bubalus bubalus.
AB  - Interferon-a genes were cloned from six breeds of three species of two genera
      (three Chinese native cattle breeds of yellow cattle, wild yak and HuanHu
      domestic yak, one European breed of Holstein cow, and two water buffalo breeds of
      FuAn water buffalo and FuZhong water buffalo) by direct PCR. The PCR products
      were directly inserted into the expression vector to be sequenced and expressed.
      Sequence analysis showed that IFN-a genes of six clones were composed of 498
      nucleotides, encoding a mature polypeptide with 166 amino acids. Compared with
      the published BoIFN-a subtypes, the IFN-a gene of Holstein cow had only one point
      mutation with the BoIFN-aA subtype. The IFN-a gene of yellow cattle was similar
      to the BoIFN-aD subtype with amino acid identity of 97.0% and may be considered
      as a new subtype, namely, BoIFN-aD1. The other four IFN-a genes, cloned from wild
      yak and HuanHu domestic yak, FuAn water buffalo, and FuZhong water buffalo,
      represented four new subtypes, namely, BoIFN-aI, BoIFN-aJ, BuIFN-a1, and BuIFN
      a2, respectively. Each of the six clones was expressed in E. coli with molecular
      weight of approximately 20 kDa by SDS-PAGE and Western blot analyses. Antiviral
      activity assays showed that the six recombinant IFN-a (rIFN-a) all exhibited
      1,000 times higher antiviral activity in the MDBK/VSV cell line than in the
      CEF/VSV one. Moreover, the rIFN-as could inhibit infectious bovine
      rhinotracheitis virus replication in the MDBK cell line using CPE inhibition
      method. The results suggested that rIFN-as a potential agent for clinical
      application against virus diseases in cattle industry.

PMID- 16621761
TI  - Single nucleotide polymorphisms for integrative mapping in the Turkey (Meleagris
      gallopavo).
AB  - When multiple genetic maps exist for a species, integration of these maps
      requires a set of common markers be genotyped across the individual mapping
      populations. In the turkey, three genetic maps based on separate mapping
      populations are available. In this study, SNP-based markers were developed for
      integrating the cDNA/RFLP-based map (1) with microsatellite markers of the second
      generation turkey genome map (2). Forty-eight primer sets were designed and
      tested and 33 (69%) correctly amplified turkey genomic DNA by PCR. Putative SNPs
      were detected in 20 (61%) of the amplified gene fragments, and 10 SNP markers
      were subsequently genotyped by PCR/RFLP for segregation analysis. Eight SNP
      markers were incorporated into the turkey genetic map.

PMID- 16621762
TI  - Relationship between immune cell phenotypes and pig growth in a commercial farm.
AB  - The objective of this study was to evaluate the relationship between the level
      and function of circulating immune cells with average daily gain, live and
      carcass measurements, feed intake, and feed conversion. Production performance
      was monitored throughout the pig's lifetime. Pigs were moved in weekly batches
      through the nursery and growing/finishing rooms at specific target weights.
      Animals were individually weighed at birth and at weaning, and then every two
      weeks while they were "on test" until they were "off test" and sent to the
      slaughterhouse. At six to seven weeks of age, the pigs were bled in the nursery.
      The percentage of immune cell subsets and lymphocyte proliferation was estimated
      using swine monoclonal antibodies and flow cytometric analysis. The predictive
      effect of the immune cell subset markers and lymphocyte proliferation on
      production traits was statistically analyzed. The results indicated that the
      proportion of several peripheral cell subsets, including CD16+, CD2+/CD16+, and
      CD8+ lymphocytes, appear to predict growth during the entire productive life of
      the pig. Larger percentages of lymphocytes expressing CD16+ CD2+/CD16+, and
      CD8+receptors in blood resulted in a reduction in average daily gain. In
      addition, high percentages of SLA-DQ+ cells were associated with better carcass
      weight and feed conversion. The CD16+, CD2+/CD16+, CD8+, and SLA-DQ+/- cell
      subsets appear to be important biomarkers involved with the inherent ability of
      the pig to efficiently grow and produce better carcass weight in representative
      commercial environments.

PMID- 16621763
TI  - Sequence identification, tissue distribution, mapping and polymorphism of the
      porcine sar1b gene.
AB  - The predicted full-length cDNA sequence of the porcine Sar1b gene was
      characterized by assembling pig ESTs from GenBank. The coding sequence (CDS)
      shares high sequence identity with the corresponding sequences of human (93%) and
      mouse (91%). The reverse transcription-polymerase chain reaction (RT-PCR)
      displayed that porcine Sar1b gene is expressed in all eight tissues (liver, small
      intestine, stomach, heart, lung, spleen, muscle and fat). Analysis of the somatic
      cell hybrid panel (SCHP) and the INRA-University of Minnesota porcine radiation
      hybrid (IMpRH) panel indicated the gene maps to SSC2 (1/2 q24)-q29 and most
      closely links to the interleukin-4 (IL4) gene. One base-pair deletion
      polymorphism in the 3' untranslated region (UTR) detected by PCR-single strand
      conformational polymorphism (PCR-SSCP) analysis shows allele frequency
      differences between Meishan, Yushan Black, Dahuabai, Qingping, Tibetan, Landrace,
      Large White and Duroc. The association analysis using pigs of Tongcheng, Landrace
      x (Large White x Tongcheng) and Large White x (Landrace x Tongcheng) suggested
      that the deletion polymorphism was associated with the porcine muscle pH value.

PMID- 16621764
TI  - Evaluation of worker exposure to TDI, MOCA, and methylene chloride.

PMID- 16621766
TI  - Estimation of respirable dust exposure among coal miners in South Africa.
AB  - The use of retrospective occupational hygiene data for epidemiologic studies is
      useful in determining exposure-outcome relationships, but the potential for
      exposure misclassification is high. Although dust sampling in the South African
      coal industry has been a legal requirement for several decades, these historical
      data are not readily adequate for estimating past exposures. This study describes
      the respirable coal mine dust levels in three South African coal mines over time.
      Each of the participating mining operations had well-documented dust sampling
      information that was used to describe historical trends in dust exposure.
      Investigator-collected personal dust samples were taken using standardized
      techniques from the face, backbye (underground jobs not at the coal face), and
      surface from 50 miners at each mine, repeated over three sampling cycles. Job
      histories and exposure information was obtained from a sample of 684 current
      miners and 188 ex-miners. Linear models were developed to estimate the exposure
      levels associated with work in each mine, exposure zone, and over time using a
      combination of operator-collected historical data and investigator-collected
      samples. The estimated levels were then combined with work history information to
      calculate cumulative exposure metrics for the miner cohort. The mean historical
      and investigator-collected respirable dust levels were within international norms
      and South African standards. Silica content of the dust samples was also below
      the 5% regulatory action level. Mean respirable dust concentrations at the face,
      based on investigator-collected samples, were 0.9 mg/m(3), 1.3 mg/m(3), and 1.9
      mg/m(3) at Mines 1, 2, and 3, respectively. The operator-collected samples showed
      considerable variability across exposure zones, mines, and time, with the annual
      means at the face ranging from 0.4 mg/m(3) to 2.9 mg/m(3). Statistically
      significant findings were found between operator- and investigator-collected dust
      samples. Model-based arithmetic mean dust estimates at the face were 1.2 mg/m(3),
      2.0 mg/m(3), and 0.9 mg/m(3) for Mines 1, 2, and 3, respectively. Using these
      levels, the mean cumulative exposure for the cohort was 56.8 mg-years/m(3).
      Current miners had a mean cumulative exposure of 66.5 mg-years/m(3), compared
      with ex-miners of 26.8 mg-years/m(3). Improvements in dust management or the use
      of different sampling equipment could account for the significant differences
      seen between operator- and investigator-collected data. Regression modeling for
      estimating mean dust levels over time using combined historical and investigator
      collected data seems a reasonable method and useful in constructing models to
      describe cumulative exposures in a cohort of current and ex-miners.

PMID- 16621767
TI  - Hypersensitivity pneumonitis in a hardwood processing plant related to heavy mold
      exposure.
AB  - Two workers employed in a hardwood floor plant presented symptoms suggestive of
      hypersensitivity pneumonitis (HP). At that plant, kiln-dried wood often shows
      moldy growth and is subsequently brought inside for processing. This study
      evaluated the environment in attempt to identify the causative antigen and verify
      whether other workers of this and similar plants had or were at risk of
      developing HP. Dust from dust-removing systems and molds on the surface of wood
      planks were collected and air samples taken from a sister plant. Blood samples,
      spirometry, and symptoms' questionnaires were obtained from 11 co-workers. Dense
      Paecilomyces growth was observed on the surface of the dried processed wood in
      the index plant. This fungal genus was not detected in the sister plant. An
      additional worker had symptoms suggestive of HP, and his bronchoalveolar lavage
      revealed a lymphocytic alveolitis. The 3 confirmed cases of HP and the other 10
      workers had positive specific IgG antibodies to Paecilomyces. We report 3 cases
      of HP out of 13 workers and a 100% sensitization to molds in workers of a
      hardwood processing plant. This rate is much higher than what is commonly seen in
      other environments associated with HP. The drying process is suspected of being
      responsible for the massive Paecilomyces contamination likely responsible for the
      HP.

PMID- 16621768
TI  - Effects of oral glutamine supplementation on children with solid tumors receiving
      chemotherapy.
AB  - In recent years, there have been reports that glutamine support improves immune
      functions in adult patients with malignancy, but there is a lack of data in
      children. Oral glutamine support of 4 g/m2/day was given to 21 children with
      various solid tumors, aged 1-17 years (9.86 +/- 5.38) for all 5 days of a
      chemotherapy course. The same parameters in another course of the same protocol
      without glutamine supplementation were considered as controls. There were
      significant improvements of some nutritional and immunological parameters in the
      glutamine-supplemented course. Also glutamine seemed to reduce antibiotic
      necessity. Oral glutamine supplementation could be considered in children with
      solid tumors receiving chemotherapy.

PMID- 16621769
TI  - Alpha-fetoprotein following neonatal resection of sacrococcygeal teratoma.
AB  - The sacrococcygeal teratoma (SCT) is the most frequent tumor in the neonatal
      period. Alpha-fetoprotein (AFP) levels fall after tumoral resection, although the
      time required for level normalization has not been established. The authors
      evaluate the time required for AFP levels to reach normal levels in 6 infants
      with prenatal diagnosis of SCT who underwent surgery for resection. The mean time
      required for AFP level normalization was 9 months. All patients were alive and 1
      had neurogenic bladder. AFP has a progressive decrease, which may last 9 months
      in average and should not be confused with tumoral relapse.

PMID- 16621770
TI  - Serum pro-hepcidin levels and relationships with iron parameters in healthy
      preterm and term newborns.
AB  - A recently isolated peptide hormone, hepcidin, is thought to be the principal
      regulator of iron homeostasis. Hepcidin acts by limiting intestinal iron
      absorption and promoting iron retention in reticuloendothelial cells. Its
      precursor peptide form is called pro-hepcidin. The aims of this study were to
      determine serum pro-hepcidin levels in healthy preterm and term newborns, and to
      assess possible relationships between pro-hepcidin and serum iron, serum
      ferritin, and transferrin. A serum sample was collected from each of 26 healthy
      preterm (gestational age < 37 weeks) and 16 healthy, full-term, appropriate-for
      gestational age babies. The preterm babies were also divided into 2 subgroups
      based on gestational age. Samples were analyzed for complete blood count, serum
      iron and ferritin concentrations, iron-binding capacity, and transferrin and pro
      hepcidin levels. Group findings were compared and correlations between pro
      hepcidin and the iron parameters were tested. The respective serum pro-hepcidin
      levels (mean +/- SD) in the 16 healthy term and 26 healthy preterm newborns were
      482 +/- 371.9 ng/mL and 496.7 +/- 443.5 ng/mL. Analysis revealed no significant
      correlations between serum pro-hepcidin level and serum iron, serum ferritin, or
      transferrin in the preterm or term newborns. Pro-hepcidin levels were not
      correlated with gestational age in the preterm group. The results indicate that
      healthy preterm and term newborns have high pro-hepcidin levels.

PMID- 16621771
TI  - Automated reticulocyte response is a good predictor of bone-marrow recovery in
      pediatric malignancies.
AB  - The authors attempted to establish the benefits of flow cytometry-based
      reticulocyte analysis over absolute neutrophil count (ANC) recovery. Serial
      hemograms of 18 pediatric cases of hematologic malignancies were analyzed until
      day 35 of chemotherapy. Immature reticulocyte fraction (IRF) showed early
      recovery in 44.4% of cases compared to ANC. Since reticulocyte fractions are not
      influenced by infections, they are a better parameter of bone marrow regeneration
      than ANC. The study shows that IRF can act as a harbinger of regenerating bone
      marrow activity in patients with persistent neutropenia and guide the modulation
      of antibiotic strategies in these patients.

PMID- 16621772
TI  - The usefulness of glycosylated hemoglobin (HbA1C) in discriminating between iron
      deficiency and thalassemia.
AB  - This study assessed whether glycosylated hemoglobin could be used as an index to
      distinguish between iron-deficiency anemia and thalassemia minor. Glycosylated
      hemoglobin was measured by high-pressure liquid chromatography in 40 ss 
      thalassemia minor patients, 20 iron-deficiency anemia patients, and 38 healthy
      controls, all nondiabetic. Median glycosylated hemoglobin was lower in ss 
      thalassemia minor than in the iron-deficiency and control groups (p = .000).
      There was no difference between iron-deficiency patients and healthy controls (p
      = .095). Glycosylated hemoglobin was not different in iron-replete and iron
      deficient traits (p > .05). A cutoff value of 5% has provided a sensitivity of
      95% and specificity of 75.7% for distinguishing between these two entities.
      Positive and negative predictive value were 96.6 and 67.9%. These values were
      superior to the traditional discriminants' values calculated on the same
      individuals. Glycosylated hemoglobin could be useful in discriminating between
      iron-deficiency anemia and thalassemia minor. Further studies are needed, but the
      point that it can also be used when both conditions exist simultaneously seems to
      be clinically important.

PMID- 16621773
TI  - Successful treatment of spinal cord compression secondary to extramedullary
      hematopoietic mass by hypertransfusion in a patient with thalassemia major.
AB  - A 15-year-old girl with thalassemia major who suffered from paraparesis with a
      history of progressive lower limb weakness for 2 years immigrated from mainland
      China to Hong Kong. She had not received regular blood transfusion since the age
      of 6 years after splenectomy. MRI of the spine showed thoracic spinal cord
      compression secondary to extramedullary hematopoietic mass. She made significant
      recovery with hypertransfusion therapy alone. MRI of the spine repeated 3 months
      later showed nearly complete resolution of the extramedullary hematopoietic mass.

PMID- 16621774
TI  - Nosocomial pulmonary Rhizopus diagnosed by bronchoalveolar lavage with cytology
      in a child with acute lymphoblastic leukemia.
AB  - Rhizopus species is an opportunistic fungus that is contracted by inhalation of
      aerosolized spores. Early diagnosis is often difficult but is a necessity to
      prevent rapid progression of the infection that leads to blood vessel invasion by
      hyphae, causing fatal hemoptysis. A previous case report described the utility of
      cytologic examination of bronchoalveolar lavage (BAL) fluid in achieving a prompt
      diagnosis of Rhizopus species in an adolescent patient with diabetic
      ketoacidosis. The author presents a case that further describes the benefit of
      performing BAL fluid cytology to help identify fungal morphology characteristics
      in order to reach an expeditious diagnosis of Rhizopus species in a leukemia
      patient.

PMID- 16621775
TI  - Improved outcome in South African children of mixed ethnicity treated for all.
AB  - A historical cohort study with an analytical component was conducted to determine
      whether risk-appropriate chemotherapy can improve survival in children of mixed
      ethnicity with ALL. Eighty-one coloured children treated for ALL in South Africa
      were divided into 2 groups: group A (n = 39), treated prior to 1992, and group B
      (n = 42), treated after 1992. A comparison was made of survival, treatment
      complications, and supportive measures. The two groups were comparable. The mean
      nadirs of the white cell count (p < .01), platelet count (p = .01), and
      hemoglobin value (p < .01) were significantly lower in group B. The survival rate
      of 37% in group A improved to 66% in group B (p = .025). The results show that a
      risk-adapted regimen increased survival in children of mixed ethnicity in the
      Western Cape, despite increased hematological toxicity and episodes of febrile
      neutropenia.

PMID- 16621776
TI  - Successful treatment of acute lymphoblastic leukemia with L-asparaginase-induced
      intracranial hemorrhage to activated recombinant factor VIIa in a child.
AB  - L-Asparaginase, a major component of therapy in children with acute lymphoblastic
      leukemia, has been shown to induce coagulopathy by inhibiting synthesis of clot
      forming and clot-inhibitory proteins. The authors report the successful use of
      recombinant factor VIIa in a 15-year-old girl with acute lymphoblastic leukemia
      who had L-asparaginase-induced intracranial hemorrhage. The present case is the
      first to demonstrate use of rFVIIa in L-asparaginase-induced intracranial
      hemorrhage in a child with acute lymphoblastic leukemia.

PMID- 16621777
TI  - Transfusion-transmitted virus prevalence in Turkish patients with thalassemia.
AB  - In hematology patients on chronic transfusion regimes, liver diseases are
      frequent, and mostly related to the agents transmitted by blood products and
      concominant iron deposition in liver. Besides hepatitis B (HBV) and C (HCV)
      viruses, new viral agents like hepatitis G virus (HGV) and TorqueTeno virus (TTV)
      are identified in these patients, although their association with any pathology
      or disease is not yet proved. In the present work, the authors studied the
      clinical importance of TTV in Turkish multitransfused patients with thalassemia.
      Forty-six healthy and 57 thalassemic patients were enrolled in the study. TTV was
      detected in serum samples by 3'-UTR nested PCR. Transaminase and ferritin levels,
      hepatitis B and C virus markers and number of transfusions were interpreted for
      possible association with TTV infection. As a result, TTV was detected in 63% of
      the thalassemia and 54% of the control patients. Prevalence of TTV infection,
      clinical features, laboratory data, and annual transfusion numbers of TTV
      positive and -negative patients were not observed to be statistically
      significant. In conclusion, in Turkish patients with thalassemia, TTV infection
      cannot be considered as a risk factor for liver disease.

PMID- 16621778
TI  - Ewing sarcoma/PNET: 27 years of experience in Slovenia.
AB  - The study includes 91 patients treated for Ewing sarcoma between 1972 and 2002.
      Forty were younger and 51 were older than 16. The overall 5-year survival was
      36%: 53.5% in the younger and 22.5% in the older age group. Among patients with
      localized disease, 5-year survival was 58% in younger and 25.5% in the older.
      Survival was similar whether patients received three treatment modalities or
      chemotherapy combined with either surgery or radiotherapy. Recurrence was noted
      in 47 out of 75 patients with localized disease, most commonly as local
      recurrence or lung metastases. Among 18 evaluated patients, 14 had minor physical
      defects and 4 had severe late treatment effects (sterility in 3 and secondary
      osteogenic sarcoma in 1).

PMID- 16621779
TI  - Development and application of acute exposure guideline levels (AEGLs) for
      chemical warfare nerve and sulfur mustard agents.
AB  - Acute exposure guideline levels (AEGLs) have been developed for the chemical
      warfare agents GB, GA, GD, GF, VX, and sulfur mustard. These AEGLs were approved
      by the National Advisory Committee for Acute Exposure Guideline Levels for
      Hazardous Substances after Federal Register publication and comment, and judged
      as scientifically valid by the National Research Council Committee on Toxicology
      Subcommittee on AEGLs. AEGLs represent general public exposure limits for
      durations ranging from 10 min to 8 h, and for three levels of severity (AEGL-1,
      AEGL-2, AEGL-3). Mild effects are possible at concentrations greater than AEGL-1,
      while life-threatening effects are expected at concentrations greater than AEGL
      3. AEGLs can be applied to various civilian and national defense purposes,
      including evacuation and shelter-in-place protocols, reentry levels, protective
      clothing specifications, and analytical monitoring requirements. This report
      documents development and derivation of AEGL values for six key chemical warfare
      agents, and makes recommendations for their application to various potential
      exposure scenarios.

PMID- 16621781
TI  - Family nursing in the era of genomic health care: we should be doing so much
      more!

PMID- 16621780
TI  - Ochratoxin a: its cancer risk and potential for exposure.
AB  - Ochratoxin A (OA) is a naturally occurring mycotoxin known to contaminate a
      variety of foods and beverages. The cancer risk posed by OA was reviewed as
      relevant to human exposure, regulatory activities, and risk management efforts
      occurring worldwide, particularly in Europe. OA moves through the food chain and
      has been found in the tissues and organs of animals, including human blood and
      breast milk. Results from the National Toxicology Program's rodent bioassays show
      significantly increased incidence of mammary gland tumors in female rats and
      kidney tumors in male and female rats given OA orally. Liver tumors in female
      mice fed OA in the diet have also been observed. In humans, OA exposure has been
      most often associated with the kidney disease Balkan endemic nephropathy (BEN),
      symptoms of which include tumors of the kidney and urinary tract. No
      epidemiological studies have yet adequately evaluated the cancer risk of OA in
      human populations. Studies have shown OA to be genotoxic as well as immunotoxic,
      although its mode of action is not fully understood. Organizations and agencies
      in many countries are currently promulgating standards for OA in foods and
      beverages. Increased efforts in farm management and food safety are being made to
      mitigate the risks to public health posed by OA. The U.S. Food and Drug
      Administration (FDA) is currently evaluating data on OA levels in domestic and
      imported commodities but has not established official regulations or guidelines
      for OA in the U.S. food supply.

PMID- 16621782
TI  - Experiences of college-age youths in families with a recessive genetic condition.
AB  - Growing up in a family with a recessive genetic condition can trigger questions
      about progeny effect. This study explored perceptions of family hardiness and
      information sharing by 18- to 21-year-olds about genetic risk. Semistructured
      interviews, the Family Hardiness Index (FHI), and a Family Information Sharing
      Analog Scale (FISAS) were used. Participants included 11 youths who had relatives
      with hemophilia and 4 with sickle cell anemia. Findings revealed seven themes:
      assimilating premature knowledge; caring for others, denying self; cautioning
      during development; experiencing continual sickness; feeling less than;
      magnifying transition experiences; and sustaining by faith. There was no
      significant correlation between total FHI and FISAS. However, there was a
      statistically significant difference in FISAS between genetic condition variance.
      Specifically, higher hardiness was found and information sharing correlated among
      college youths in families with hemophilia. Additional research can lead to
      nursing interventions to provide genetic information to youths in families for
      illness variance.

PMID- 16621783
TI  - Building a new world: habits and practices of healing following the death of a
      child.
AB  - The goal of this interpretive phenomenological study is to describe and
      understand significant habits and practices developed by families bereaved from
      the sudden and unexpected loss of their children. Data were primarily collected
      through the interviewing of 15 family members in seven families. At least four
      interviews were conducted with each family. Family members were interviewed both
      together and separately. The analysis of the data illuminated the development of
      significant and meaningful family practices. These practices acknowledged the
      death of the children, integrated their loss into the everyday lives of these
      families, allowed for continuing connection, and were of utter importance as they
      contributed to family healing.

PMID- 16621784
TI  - Families and withdrawal of life-sustaining therapy: state of the science.
AB  - As the science progresses related to families participating in the process of
      withdrawal of life-sustaining therapy (LST), it is important to assess research
      accomplishments, identify gaps in the knowledge and ways to build on the science,
      and suggest new directions for future research. Research-based articles related
      to families participating in the process of withdrawal of LST were obtained by
      conducting computer-assisted searches and analyzing references lists. A grid was
      developed that included key variables from each of the studies. A second grid was
      developed and included the subthemes that evolved from the analysis. Eleven
      studies were reviewed and analyzed. Themes that evolved include illness context,
      family context, and family and health care provider interactions. Important
      information has been discovered about the family decision-making process and
      helpful health care provider interactions. Additional research focused on
      withdrawal of LST is needed to understand important concepts, develop
      instruments, and test interventions.

PMID- 16621785
TI  - Place and space: the where and why of drug-use location among rural African
      American women.
AB  - Increasing drug use among rural African American women and its effect on children
      warrants investigation. This article describes drug-use locations of rural
      African American women who use cocaine and construct their lives to conceal it
      from children. During 4 years, a 30-respondent ethnography was conducted. Data
      from in-depth interviews and field notes were analyzed for recurrent themes and
      patterns of drug-use location using NVivo. Most respondents with children used
      most often outside their households. One third (n = 10) used within their
      households when children were away or in designated spaces off limits to
      children. More respondents (n = 11) without children at home used in non
      designated spaces; in contrast, few respondents (n = 2) with children at home
      used in non-designated spaces within the household. Most respondents thought they
      were successful at concealing their cocaine use. Implications for choice of space
      and place of drug use for themselves and their children are discussed.

PMID- 16621786
TI  - Conversations in context: cultural safety and reflexivity in child and family
      health nursing.
AB  - Over 10 years, a number of nurse educators at the Waikato Institute of Technology
      (WINTEC) have worked collaboratively across primary health, cultural safety, and
      child and family health domains of the nursing curriculum. They share a common
      philosophy underpinned by notions of diversity and health equity. The philosophy
      informs their theoretical inquiry, practice and research interests, and
      pedagogical concerns. This article outlines some key aspects of their practice as
      nurse educators and researchers committed to the needs of their specific region
      in the central North Island of Aotearoa New Zealand. They begin by situating
      themselves within the region, its people, and influences before moving into a
      consideration of the wider political and policy environment. They consider the
      destabilizing effects of cultural safety education and the tension between
      biculturalism and multiculturalism in their context. Finally, they reflect on how
      these ideas inform their work with postgraduate child and family nurses.

PMID- 16621788
TI  - Identification of distinct inhibin and transforming growth factor beta-binding
      sites on betaglycan: functional separation of betaglycan co-receptor actions.
AB  - Betaglycan is a co-receptor that mediates signaling by transforming growth factor
      beta (TGFbeta) superfamily members, including the distinct and often opposed
      actions of TGFbetas and inhibins. Loss of betaglycan expression, or abrogation of
      betaglycan function, is implicated in several human and animal diseases, although
      both betaglycan actions and the ligands involved in these disease states remain
      unclear. Here we identify a domain spanning amino acids 591-700 of the betaglycan
      extracellular domain as the only inhibin-binding region in betaglycan. This
      binding site is within the betaglycan ZP domain, but inhibin binding is not
      integral to the ZP motif of other proteins. We show that the inhibin and TGFbeta
      binding residues of this domain overlap and identify individual amino acids
      essential for binding of each ligand. Mutation of Val614 to Tyr abolishes both
      inhibin and TGFbeta binding to this domain. Full-length betaglycan V614Y, and
      other mutations, retain TGFbeta binding activity via a distinct site, but are
      unable to bind inhibin-A. These betaglycan mutants fail to mediate inhibin
      antagonism of activin signaling but can present TGFbeta to TbetaRII. Separating
      the co-receptor actions of betaglycan toward inhibin and TGFbeta will allow the
      clarification of the role of betaglycan in disease states such as renal cell
      carcinoma and endometrial adenocarcinoma.

PMID- 16621789
TI  - A dishevelled-1/Smad1 interaction couples WNT and bone morphogenetic protein
      signaling pathways in uncommitted bone marrow stromal cells.
AB  - Genetic evidence from both humans and mice suggests that Wnt/beta-catenin and
      bone morphogenetic protein (BMP) signaling pathways are essential for bone marrow
      mesenchymal stem cells to differentiate into osteoblasts. Here we describe a
      mechanism through which BMPs antagonize Wnt signaling and retard bone marrow
      mesenchymal stem cell proliferation. Treatment with Wnt3a, but not BMP-2,
      stimulated Lef1-mediated transcriptional activity, whereas co-stimulation with
      both Wnt3a and BMP-2 markedly reduced Wnt3a-induced reporter activity.
      Immunoprecipitation assays in 293T cells transfected with individual Smads and
      Wnt pathway components revealed a specific interaction between Dvl-1 and Smad1
      that was dependent on the presence of Wnt3a or BMP-2. Under unstimulated
      conditions, Dvl-1 and Smad1 are co-immunoprecipitated and form a complex through
      the linker region of Smad1. Wnt3a treatment transiently disrupted the Dvl-1/Smad1
      interaction coincident with nuclear accumulation of beta-catenin. In contrast,
      when cells were exposed to both Wnt3a and BMP-2, there was an enhanced
      accumulation of the Dvl-1-Smad1 complex and a decreased nuclear accumulation of
      beta-catenin. Expression of a mutant Smad1 protein, which cannot be
      phosphorylated in response to BMP, eliminated the inhibitory effect of BMP on Wnt
      inducedbeta-catenin accumulation and transcriptional activity. These results
      identify a potential mechanism whereby BMP-2 antagonizes Wnt signaling in
      osteoblast progenitors by promoting an interaction between Smad1 and Dvl-1 that
      restricts beta-catenin activation.

PMID- 16621790
TI  - The ubiquitin-like protein MNSFbeta regulates ERK-MAPK cascade.
AB  - MNSFbeta is a ubiquitously expressed member of the ubiquitin-like family that has
      been implicated in various biological functions. Previous studies have
      demonstrated that MNSFbeta covalently binds to intracellular proapoptotic protein
      Bcl-G in mitogen-activated murine T cells. In this study, we further investigated
      the intracellular mechanism of action of MNSFbeta in macrophage cell line, Raw
      264.7 cells. We present evidence that MNSFbeta.Bcl-G complex associates with ERKs
      in non-stimulated Raw 264.7. We found that MNSFbeta.Bcl-G directly bound to ERKs
      and inhibited ERK activation by MEK1. In Raw 264.7 cells treated with MNSFbeta
      small interfering RNA (siRNA) lipopolysaccharide (LPS)-induced ERK1/2 activation
      was enhanced and LPS-induced JNK and p38 activation was unaffected. SiRNA
      mediated knockdown of MNSFbeta increased tumor necrosis factor alpha (TNFalpha)
      expression at mRNA and protein levels in LPS-stimulated Raw 264.7 cells. Finally,
      we found that transfection with MNSFbeta expression construct resulted in a
      significant inhibition of LPS-induced ERK activation and TNFalpha production. Co
      transfection experiments with MNSFbeta and Bcl-G greatly enhanced this
      inhibition. Collectively, these findings indicate that MNSFbeta might be
      implicated in the macrophage response to LPS.

PMID- 16621791
TI  - Kinetic investigation of Escherichia coli RNA polymerase mutants that influence
      nucleotide discrimination and transcription fidelity.
AB  - Recent RNA polymerase (RNAP) structures led to a proposed three-step model of
      nucleoside triphosphate (NTP) binding, discrimination, and incorporation. NTPs
      are thought to enter through the secondary channel, bind to an E site, rotate
      into a pre-insertion (PS) site, and ultimately align in the catalytic (A) site.
      We characterized the kinetics of correct and incorrect incorporation for several
      Escherichia coli RNAPs with substitutions in the proposed NTP entry pore
      (secondary channel). Substitutions of the semi-conserved residue betaAsp(675),
      which is >10A away from these sites, significantly reduce fidelity; however,
      substitutions of the totally conserved residues betaArg(678) and betaAsp(814) do
      not significantly alter the correct or incorrect incorporation kinetics, even
      though the corresponding residues in RNAPII crystal structures appear to be
      interacting with the NTP phosphate groups and coordinating the second magnesium
      ion in the active site, respectively. Structural analysis suggests that the lower
      fidelity of the betaAsp(675) mutants most likely results from reduction of the
      negative potential of a small pore between the E and PS sites and elimination of
      several structural interactions around the pore. We suggest a mechanism of
      nucleotide discrimination that is governed both by rotation of the NTP through
      this pore and subsequent rearrangement or closure of RNAP to align the NTP in the
      A site.

PMID- 16621792
TI  - Membrane localization of adenomatous polyposis coli protein at cellular
      protrusions: targeting sequences and regulation by beta-catenin.
AB  - Adenomatous polyposis coli protein (APC) translocates to, and stabilizes, the
      plus-ends of microtubules. In microtubule-dependent cellular protrusions, APC
      frequently accumulates in peripheral clusters at the basal membrane. APC
      targeting to membrane clusters is important for cell migration, but the
      localization mechanism is poorly understood. In this study, we performed deletion
      mapping and defined a minimal sequence (amino acids 1-2226) that efficiently
      targets APC to membrane clusters. This sequence lacks DLG-1 and EB1 binding
      sites, suggesting that these partners are not absolutely required for APC
      membrane targeting. A series of APC sequences were transiently expressed in cells
      and compared for their ability to compete endogenous APC at the membrane; potent
      inhibition of endogenous APC targeting was elicited by the Armadillo- (binds
      KAP3A, B56alpha, and ASEF) and beta-catenin-binding domains. The Armadillo domain
      was predicted to inhibit APC membrane localization through sequestration of the
      kinesin-KAP3A complex. The role of beta-catenin in APC membrane localization was
      unexpected but affirmed by overexpressing the APC binding sequence of beta
      catenin, which similarly reduced APC membrane staining. Furthermore, we used RNA
      interference to show that loss of beta-catenin reduced APC at membrane clusters
      in migrating cells. In addition, we report that transiently expressed APC-yellow
      fluorescent protein co-localized with beta-catenin, KAP3A, EB1, and DLG-1 at
      membrane clusters, but only beta-catenin stimulated APC anchorage at the
      membrane. Our findings identify beta-catenin as a regulator of APC targeting to
      membrane clusters and link these two proteins to cell migration.

PMID- 16621794
TI  - All but the shortest polymorphic forms of the viral receptor DC-SIGNR assemble
      into stable homo- and heterotetramers.
AB  - Polymorphisms that affect the length of the extracellular neck region of the
      endothelial receptor DC-SIGNR (dendritic cell-specific intercellular adhesion
      molecule-3-grabbing nonintegrin-related protein) have been linked to differences
      in susceptibility to infection by enveloped viruses. We have characterized the
      effects of these polymorphisms on the ability of DC-SIGNR to form tetramers
      containing the clusters of sugar-binding sites needed for binding to viral
      envelope glycoproteins. Chemical cross-linking and analytical ultracentrifugation
      experiments have been used to show that only the smallest form of DC-SIGNR is
      defective in homotetramer assembly. A novel affinity-tagging approach has been
      employed to demonstrate that, contrary to previous speculation, heterotetramers
      can be assembled efficiently from DC-SIGNR polypeptides of different lengths. The
      heterotetramers are stable and can be detected in fibroblasts transfected with
      multiple forms of DC-SIGNR. These results provide a molecular basis for
      interpreting the way polymorphisms affect interactions with viruses.

PMID- 16621793
TI  - Functional repression of cAMP response element in 6-hydroxydopamine-treated
      neuronal cells.
AB  - Impaired survival signaling may represent a central mechanism in
      neurodegeneration. 6-Hydroxydopamine (6-OHDA) is an oxidative neurotoxin used to
      injure catecholaminergic cells of the central and peripheral nervous systems.
      Although 6-OHDA elicits phosphorylation of several kinases, downstream
      transcriptional effects that influence neuronal cell death are less defined. The
      cAMP response element (CRE) is present in the promoter sequences of several
      important neuronal survival factors. Treatment of catecholaminergic neuronal cell
      lines (B65 and SH-SY5Y) with 6-OHDA resulted in repression of basal CRE
      transactivation. Message levels of CRE-driven genes such as brain-derived
      neurotrophic factor and the survival factor Bcl-2 were decreased in 6-OHDA
      treated cells, but message levels of genes lacking CRE sequences were not
      affected. Repression of CRE could be reversed by delayed treatment with cAMP
      several hours after initiation of 6-OHDA injury. Furthermore, restoration of CRE
      driven transcription was associated with significant neuroprotection. In contrast
      to observations in other model systems, the mechanism of CRE repression did not
      involve decreased phosphorylation of its binding protein CREB. Instead, total
      CREB and phospho-CREB (pCREB) were increased in the cytoplasm and decreased in
      the nucleus of 6-OHDA-treated cells. 6-OHDA also decreased nuclear pCREB in
      dopaminergic neurons of primary mouse midbrain cultures. Co-treatment with cAMP
      promoted/restored nuclear localization of pCREB in both immortalized and primary
      culture systems. Increased cytoplasmic pCREB was observed in degenerating human
      Parkinson/Lewy body disease substantia nigra neurons but not in age-matched
      controls. Notably, cytoplasmic accumulation of activated upstream CREB kinases
      has been observed previously in both 6-OHDA-treated cells and degenerating human
      neurons, supporting a potential role for impaired nuclear import of
      phosphorylated signaling proteins.

PMID- 16621795
TI  - ATP binding to a unique site in the type-1 S2- inositol 1,4,5-trisphosphate
      receptor defines susceptibility to phosphorylation by protein kinase A.
AB  - The subtype- and splice variant-specific modulation of inositol 1,4,5
      trisphosphate receptors (InsP3R) by interaction with cellular factors plays a
      fundamental role in defining the characteristics of Ca2+ release in individual
      cell types. In this study, we investigate the binding properties and functional
      consequences of the expression of a putative nucleotide binding fold (referred to
      as the ATPC site) unique to the S2- splice variant of the type-1 InsP3R (InsP3R
      1), the predominant splice variant in peripheral tissue. A glutathione S
      transferase fusion protein encompassing amino acids 1574-1765 of the S2- InsP3R-1
      and including the glycine-rich motif Gly-Tyr-Gly-Glu-Lys-Gly bound ATP
      specifically as measured by fluorescent trinitrophenyl-ATP binding. This binding
      was completely abrogated by a point mutation (G1690A) in the nucleotide binding
      fold. The functional sensitivity of S2- InsP3R-1 constructs was evaluated in DT40
      3KO-M3 cells, a null background for InsP3R, engineered to express muscarinic M3
      receptors. The S2- InsP3R-1 containing the G1690A mutation was markedly less
      sensitive to agonist stimulation than wild type S2- InsP3R-1 or receptors
      containing a similar (Gly --> Ala) mutation in the established nucleotide binding
      sites in InsP3R-1 (the ATPA and ATPB sites). The ATP sensitivity of InsP3-induced
      Ca2+ release, however, was not altered by the G1690A mutation when measured in
      permeabilized DT40-3KO cells, suggesting a unique role for the ATPC site. Ca2+
      release was dramatically potentiated following activation of cAMP-dependent
      protein kinase in DT40-3KO cells transiently expressing wild type S2- InsP3R or
      Gly --> Ala mutations in the ATPA and ATPB sites, but phosphorylation of the
      receptor and the potentiation of Ca2+ release were absent in cells expressing the
      G1690A mutation in S2- InsP3R. These data indicate that ATP binding specifically
      to the ATPC site in S2- InsP3R-1 controls the susceptibility of the receptor to
      protein kinase A-mediated phosphorylation, contributes to the functional
      sensitivity of the S2- InsP3R-1 and ultimately the sensitivity of cells to
      agonist stimulation.

PMID- 16621796
TI  - Alternative splicing controls neuronal expression of v-ATPase subunit a1 and
      sorting to nerve terminals.
AB  - Vacuolar proton ATPase accumulates protons inside various intracellular
      organelles such as synaptic vesicles; its membrane domain V0 could also be
      involved in membrane fusion. These different functions could require vacuolar
      proton ATPases possessing different V0 subunit a isoforms. In vertebrates, four
      genes encode isoforms a1-a4, and a1 variants are also generated by alternative
      splicing. We identified a novel a1 splice variant a1-IV and showed that the two
      a1 variants containing exon C are specifically expressed in neurons. Single
      neurons coexpress a2, a1-I, and a1-IV, and these subunit a isoforms are targeted
      to different membrane compartments. Recombinant a2 was accumulated in the trans
      Golgi network, and a1-I was concentrated in axonal varicosities, whereas a1-IV
      was sorted to both distal dendrites and axons. Our results indicate that
      alternative splicing of exon N controls differential sorting of a1 variants to
      nerve terminals or distal dendrites, whereas exon C regulates their neuronal
      expression.

PMID- 16621797
TI  - Selective inhibition of endoplasmic reticulum-associated degradation rescues
      DeltaF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8
      levels: therapeutic implications.
AB  - Endoplasmic reticulum (ER)-associated degradation (ERAD) is the major quality
      control pathway of the cell. The most common disease-causing protein folding
      mutation, DeltaF508-cystic fibrosis transmembrane regulator (CFTR), is destroyed
      by ERAD to cause cystic fibrosis (CF). p97/valosin-containing protein (VCP)
      physically interacts with gp78/autocrine motility factor receptor to couple
      ubiquitination, retrotranslocation, and proteasome degradation of misfolded
      proteins. We show here that p97/VCP and gp78 form complexes with CFTR during
      translocation from the ER for degradation by the cytosolic proteasome.
      Interference in the VCP-CFTR complex promoted accumulation of immature CFTR in
      the ER and partial rescue of functional chloride channels to the cell surface.
      Moreover, under these conditions, interleukin-8 (IL8), the expression of which is
      regulated by the proteasome, was reduced. Inhibition of the proteasome with
      bortezomib (PS-341/Velcade) also rescued CFTR, but with less efficiency, and
      suppressed NFkappaB-mediated IL8 activation. The inhibition of the major stress
      inducible transcription factor CHOP (CCAAT/enhancer-binding protein homologous
      protein)/GADD153 together with bortezomib was most effective in repressing
      NFkappaB-mediated IL8 activation compared with interference of VCP, MLN-273
      (proteasome inhibitor), or 4-phenylbutyrate (histone deacetylase inhibitor).
      Immunoprecipitation of DeltaF508-CFTR from primary CF bronchial epithelial cells
      confirmed the interaction with VCP and associated chaperones in CF. We conclude
      that VCP is an integral component of ERAD and cellular stress pathways induced by
      the unfolded protein response and may be central to the efficacy of CF drugs that
      target the ubiquitin-proteasome pathway.

PMID- 16621798
TI  - Amino acid starvation induces the SNAT2 neutral amino acid transporter by a
      mechanism that involves eukaryotic initiation factor 2alpha phosphorylation and
      cap-independent translation.
AB  - Nutritional stress caused by amino acid starvation involves a coordinated
      cellular response that includes the global decrease of protein synthesis and the
      increased production of cell defense proteins. Part of this response is the
      induction of transport system A for neutral amino acids that leads to the
      recovery of cell volume and amino acid levels once extracellular amino acid
      availability is restored. Hypertonic stress also increases system A activity as a
      mechanism to promote a rapid recovery of cell volume. Both a starvation-dependent
      and a hypertonic increase of system A transport activity are due to the induction
      of SNAT2, the ubiquitous member of SLC38 family. The molecular mechanisms
      underlying SNAT2 induction were investigated in tissue culture cells. We show
      that the increase in system A transport activity and SNAT2 mRNA levels upon amino
      acid starvation were blunted in cells with a mutant eIF2alpha that cannot be
      phosphorylated. In contrast, the induction of system A activity and SNAT2 mRNA
      levels by hypertonic stress were independent of eIF2alpha phosphorylation. The
      translational control of the SNAT2 mRNA during amino acid starvation was also
      investigated. It is shown that the 5'-untranslated region contains an internal
      ribosome entry site that is constitutively active in amino acid-fed and 
      deficient cells and in a cell-free system. We also show that amino acid
      starvation caused a 2.5-fold increase in mRNA and protein expression from a
      reporter construct containing both the SNAT2 intronic amino acid response element
      and the SNAT2-untranslated region. We conclude that the adaptive response of
      system A activity to amino acid starvation requires eukaryotic initiation factor
      2alpha phosphorylation, increased gene transcription, and internal ribosome entry
      site-mediated translation. In contrast, the response to hypertonic stress does
      not involve eukaryotic initiation factor 2alpha phosphorylation, suggesting that
      SNAT2 expression can be modulated by specific signaling pathways in response to
      different stresses.

PMID- 16621799
TI  - Post-translational modifications of the four conserved lysine residues within the
      collagenous domain of adiponectin are required for the formation of its high
      molecular weight oligomeric complex.
AB  - Adiponectin is a multifunctional adipokine that circulates as several oligomeric
      complexes in the blood stream. However, the molecular basis that regulates the
      production of the adiponectin oligomers remains largely elusive. We have shown
      previously that several conserved lysine residues (positions 68, 71, 80, and 104)
      within the collagenous domain of adiponectin are modified by hydroxylation and
      glycosylation (Wang, Y., Xu, A., Knight, C., Xu, L. Y., and Cooper, G. J. (2002)
      J. Biol. Chem. 277, 19521-19529). Here, we investigated the potential roles of
      these post-translational modifications in oligomeric complex formation of
      adiponectin. Gel filtration chromatography revealed that adiponectin produced
      from mammalian cells formed trimeric, hexameric, and high molecular weight (HMW)
      oligomeric complexes. These three oligomeric forms were differentially
      glycosylated, with the HMW oligomer having the highest carbohydrate content.
      Disruption of hydroxylation and glycosylation by substitution of the four
      conserved lysines with arginines selectively abrogated the intracellular assembly
      of the HMW oligomers in vitro as well as in vivo. In type 2 diabetic patients,
      both the ratios of HMW to total adiponectin and the degree of adiponectin
      glycosylation were significantly decreased compared with healthy controls.
      Functional studies of adiponectin-null mice revealed that abrogation of lysine
      hydroxylation/glycosylation markedly decreased the ability of adiponectin to
      stimulate phosphorylation of AMP-activated protein kinase in liver tissue.
      Chronic treatment of db/db diabetic mice with wild-type adiponectin alleviated
      hyperglycemia, hypertriglyceridemia, hepatic steatosis, and insulin resistance,
      whereas full-length adiponectin without proper post-translational modifications
      and HMW oligomers showed substantially decreased activities. Taken together,
      these data suggest that hydroxylation and glycosylation of the lysine residues
      within the collagenous domain of adiponectin are critically involved in
      regulating the formation of its HMW oligomeric complex and consequently
      contribute to the insulin-sensitizing activity of adiponectin in hepatocytes.

PMID- 16621800
TI  - Identification of SNAP-47, a novel Qbc-SNARE with ubiquitous expression.
AB  - The SNARE proteins are essential components of the intracellular fusion
      machinery. It is thought that they form a tight four-helix complex between
      membranes, in effect initiating fusion. Most SNAREs contain a single coiled-coil
      region, referred to as the SNARE motif, directly adjacent to a single
      transmembrane domain. The neuronal SNARE SNAP-25 defines a subfamily of SNARE
      proteins with two SNARE helices connected by a longer linker, comprising also the
      proteins SNAP-23 and SNAP-29. We now report the initial characterization of a
      novel vertebrate homologue termed SNAP-47. Northern blot and immunoblot analysis
      revealed ubiquitous tissue distribution, with particularly high levels in nervous
      tissue. In neurons, SNAP-47 shows a widespread distribution on intracellular
      membranes and is also enriched in synaptic vesicle fractions. In vitro, SNAP-47
      substituted for SNAP-25 in SNARE complex formation with the neuronal SNAREs
      syntaxin 1a and synaptobrevin 2, and it also substituted for SNAP-25 in
      proteoliposome fusion. However, neither complex assembly nor fusion was as
      efficient as with SNAP-25.

PMID- 16621801
TI  - Hepatitis B virus capsid-like particles can display the complete, dimeric outer
      surface protein C and stimulate production of protective antibody responses
      against Borrelia burgdorferi infection.
AB  - Hepatitis B virus capsid-like particles (CLPs), icosahedral assemblies formed by
      90 or 120 core protein dimers, hold promise as immune-enhancing vaccine carriers
      for heterologous antigens. Insertions into the immunodominant c/e1 B cell
      epitope, a surface-exposed loop, are especially immunogenic. However, display of
      whole proteins, desirable to induce multispecific and possibly neutralizing
      antibody responses, can be restrained by an unsuitable structure of the foreign
      protein and by its propensity to undergo homomeric interactions. Here we analyzed
      CLP formation by core fusions with two distinct variants of the dimeric outer
      surface lipoprotein C (OspC) of the Lyme disease agent Borrelia burgdorferi.
      Although the topology of the termini in the OspC dimer does not match that of the
      insertion sites in the carrier dimer, both fusions, coreOspCa and coreOspCb,
      efficiently formed stable CLPs. Electron cryomicroscopy clearly revealed the
      surface disposition of the OspC domains, possibly with OspC dimerization
      occurring across different core protein dimers. In mice, both CLP preparations
      induced high-titered antibody responses against the homologous OspC variant, but
      with substantial cross-reactivity against the other variant. Importantly, both
      conferred protection to mice challenged with B. burgdorferi. These data show the
      principal applicability of hepatitis B virus CLPs for the display of dimeric
      proteins, demonstrate the presence in OspC of hitherto uncharacterized epitopes,
      and suggest that OspC, despite its genetic variability, may be a valid vaccine
      candidate.

PMID- 16621802
TI  - Opposing roles for ERK1/2 in neuronal oxidative toxicity: distinct mechanisms of
      ERK1/2 action at early versus late phases of oxidative stress.
AB  - Glutamate-induced oxidative toxicity is mediated by glutathione depletion in the
      HT22 mouse hippocampal cell line. Previous results with pharmacological agents
      implicated the extracellular signal-regulated kinases-1/2 (ERK1/2) in glutamate
      toxicity in HT22 cells and immature embryonic rat cortical neurons. In this
      report, we definitively establish a role for ERK1/2 in oxidative toxicity using
      dominant negative MEK1 expression in transiently transfected HT22 cells to block
      glutamate-induced cell death. In contrast, chronic activation of ERK (i.e.
      brought about by transfection of constitutively active ERK2 chimera) is not
      sufficient to trigger HT22 cell death demonstrating that ERK1/2 activation is not
      sufficient for toxicity. Activation of ERK1/2 in HT22 cells has a distinct
      kinetic profile with an initial peak occurring between 30 min and 1 h of
      glutamate treatment and a second peak typically emerging after 6 h. We
      demonstrate here that the initial phase of ERK1/2 induction is because of
      activation of metabotropic glutamate receptor type I (mGluRI). ERK1/2 activation
      by mGluRI contributes to an HT22 cell adaptive response to oxidative stress as
      glutamate-induced toxicity is enhanced upon pharmacological inhibition of mGluRI.
      The protective effect of ERK1/2 activation at early times after glutamate
      treatment is mediated by a restoration of glutathione (GSH) levels that are
      reduced because of depletion of intracellular cysteine pools. Thus, ERK1/2
      appears to play dual roles in HT22 cells acting as part of a cellular adaptive
      response during the initial phases of glutamate-induced oxidative stress and
      contributing to toxicity during later stages of stress.

PMID- 16621803
TI  - Physiological consequences of loss of allosteric activation of yeast NAD+
      specific isocitrate dehydrogenase.
AB  - Based on allosteric regulatory properties, NAD+-specific isocitrate dehydrogenase
      (IDH) is believed to control flux through the tricarboxylic acid cycle in vivo.
      To distinguish growth phenotypes associated with regulatory dysfunction of this
      enzyme in Saccharomyces cerevisiae, we analyzed strains expressing well defined
      mutant forms of IDH or a non-allosteric bacterial NAD+-specific isocitrate
      dehydrogenase (IDHa). As previously reported, expression of mutant forms of IDH
      with severe catalytic defects but intact regulatory properties produced an
      inability to grow with acetate as the carbon source and a dramatic increase in
      the frequency of generation of petite colonies, phenotypes also exhibited by a
      strain (idh1Deltaidh2Delta) lacking IDH. Reduced growth rates on acetate medium
      were also observed with expression of enzymes with severe regulatory defects or
      of the bacterial IDHa enzyme, suggesting that allosteric regulation is also
      important for optimal growth on this carbon source. However, expression of IDHa
      produced no effect on petite frequency, suggesting that the intermediate petite
      frequencies observed for strains expressing regulatory mutant forms of IDH are
      likely to correlate with the slight reductions in catalytic efficiency observed
      for these enzymes. Finally, rates of increase in oxygen consumption were measured
      during culture shifts from medium with glucose to medium with ethanol as the
      carbon source. Strains expressing wild-type or catalytically deficient mutant
      forms of IDH exhibited rapid respiratory transitions, whereas strains expressing
      regulatory mutant forms of IDH or the bacterial IDHa enzyme exhibited much slower
      respiratory transitions. This suggests an important physiological role for
      allosteric activation of IDH during changes in environmental conditions.

PMID- 16621804
TI  - Conserved loop sequence of helix 69 in Escherichia coli 23 S rRNA is involved in
      A-site tRNA binding and translational fidelity.
AB  - Ribosomal (r) RNAs play a crucial role in the fundamental structure and function
      of the ribosome. Helix 69 (H69) (position 1906-1924), a highly conserved stem
      loop in domain IV of the 23 S rRNA of bacterial 50 S subunits, is located on the
      surface for intersubunit association with the 30 S subunit by connecting with
      helix 44 of 16 S rRNA with the bridge B2a. H69 directly interacts with A/T-, A-,
      and P-site tRNAs during each translation step. To investigate the functional
      importance of the highly conserved loop sequence (1912-1918) of H69, we employed
      a genetic method that we named SSER (systematic selection of functional sequences
      by enforced replacement). This method allowed us to identify and select from the
      randomized loop sequences of H69 in Escherichia coli 23 S rRNA functional
      sequences that are absolutely required for ribosomal function. From a library
      consisting of 16,384 sequence variations, 13 functional variants were obtained.
      A1912 and U(Psi)1917 were selected as essential residues in all variants. An E.
      coli strain having 23 S rRNA with a U to A mutation at position 1915 showed a
      severe growth phenotype and low translational fidelity. The result could be
      explained by the fact that the A1915-ribosome variant has weak subunit
      association, weak A-site tRNA binding, and decreased translational activity. This
      study proposes that H69 plays an important role in the control of translational
      fidelity by modulating A-site tRNA binding during the decoding process.

PMID- 16621805
TI  - Hdm2 nuclear export, regulated by insulin-like growth factor-I/MAPK/p90Rsk
      signaling, mediates the transformation of human cells.
AB  - Insulin-like growth factor (IGF)-I receptor activation leads to enhanced
      proliferation and cell survival via the MAP kinase and phosphatidylinositol 3
      kinase-signaling pathways. Upon stimulation by IGF-I, the Hdm2 oncoprotein is
      phosphorylated by AKT, leading to its rapid nuclear translocation and subsequent
      inhibition of p53. We now show that IGF-I stimulation regulates the nuclear
      export of Hdm2 and p53 via the MAP kinase pathway. Inhibition of p38 MAPK or MEK
      via pharmacological means or expression of dominant negative proteins inhibited
      the cytoplasmic accumulation of Hdm2 and increased Hdm2 and p53 protein levels,
      whereas constitutively active p90Rsk promoted the nuclear export of Hdm2.
      Expression of constitutively active p90Rsk with E1A, oncogenic H-Ras, and hTERT
      resulted in the anchorage-independent growth of normal human fibroblasts. Our
      findings link p90Rsk-mediated modulation of Hdm2 nuclear to cytoplasmic shuttling
      with the diminished ability of p53 to regulate cell cycle checkpoints that
      ultimately leads to transformation.

PMID- 16621806
TI  - NMR and alanine scan studies of glucose-dependent insulinotropic polypeptide in
      water.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that
      stimulates the secretion of insulin after ingestion of food. GIP also promotes
      the synthesis of fatty acids in adipose tissue. Therefore, it is not surprising
      that numerous literature reports have shown that GIP is linked to diabetes and
      obesity-related diseases. In this study, we present the solution structure of GIP
      in water determined by NMR spectroscopy. The calculated structure is
      characterized by the presence of an alpha-helical motif between residues Ser(11)
      and Gln(29). The helical conformation of GIP is further supported by CD
      spectroscopic studies. Six GIP-(1-42)Ala(1-7) analogues were synthesized by
      replacing individual N-terminal residues with alanine. Alanine scan studies of
      these N-terminal residues showed that the GIP-(1-42)Ala(6) was the only analogue
      to show insulin-secreting activity similar to that of the native GIP. However,
      when compared with glucose, its insulinotropic ability was reduced. For the first
      time, these NMR and modeling results contribute to the understanding of the
      structural requirements for the biological activity of GIP.

PMID- 16621807
TI  - The QscR quorum-sensing regulon of Pseudomonas aeruginosa: an orphan claims its
      identity.

PMID- 16621808
TI  - Iron gate: the translocation system.

PMID- 16621809
TI  - LrhA regulates rpoS translation in response to the Rcs phosphorelay system in
      Escherichia coli.
AB  - Regulation of the Escherichia coli stationary-phase sigma factor RpoS is complex
      and occurs at multiple levels in response to different environmental stresses.
      One protein that reduces RpoS levels is the transcription factor LrhA, a global
      regulator of flagellar synthesis. Here we clarify the mechanism of this
      repression and provide insight into the signaling pathways that feed into this
      regulation. We show that LrhA represses RpoS at the level of translation in a
      manner that is dependent on the small RNA (sRNA) chaperone Hfq. Although LrhA
      also represses the transcription of the sRNA RprA, its regulation of RpoS mainly
      occurs independently of RprA. To better understand the physiological signals
      affecting this pathway, a transposon mutagenesis screen was carried out to find
      factors affecting LrhA activity levels. The RcsCDB phosphorelay system, a cell
      envelope stress-sensing pathway, was found to repress lrhA synthesis. In
      addition, mutations in the gene encoding the DNA motor protein FtsK induce lrhA
      synthesis, which may explain why such strains fail to accumulate RpoS in
      stationary phase.

PMID- 16621810
TI  - Regulatory roles for IscA and SufA in iron homeostasis and redox stress responses
      in the cyanobacterium Synechococcus sp. strain PCC 7002.
AB  - SufA, IscA, and Nfu have been proposed to function as scaffolds in the assembly
      of Fe/S clusters in bacteria. To investigate the roles of these proteins further,
      single and double null-mutant strains of Synechococcus sp. strain PCC 7002 were
      constructed by insertional inactivation of genes homologous to sufA, iscA, and
      nfu. Demonstrating the nonessential nature of their products, the sufA, iscA, and
      sufA iscA mutants grew photoautotrophically with doubling times that were similar
      to the wild type under standard growth conditions. In contrast, attempts to
      inactivate the nfu gene only resulted in stable merodiploids. These results imply
      that Nfu, but not SufA or IscA, is the essential Fe/S scaffold protein in
      cyanobacteria. When cells were grown under iron-limiting conditions, the iscA and
      sufA mutant strains exhibited less chlorosis than the wild type. Under iron
      sufficient growth conditions, isiA transcript levels, a marker for iron
      limitation in cyanobacteria, as well as transcript levels of genes in both the
      suf and isc regulons were significantly higher in the iscA mutant than in the
      wild type. Under photosynthesis-induced redox stress conditions, the transcript
      levels of the suf genes are notably higher in the sufA and the sufA iscA mutants
      than in the wild type. The growth phenotypes and mRNA abundance patterns of the
      mutant strains contradict the proposed scaffold function for the SufA and IscA
      proteins in generalized Fe/S cluster assembly and instead suggest that they play
      regulatory roles in iron homeostasis and the sensing of redox stress in
      cyanobacteria.

PMID- 16621811
TI  - Methanocaldococcus jannaschii uses a modified mevalonate pathway for biosynthesis
      of isopentenyl diphosphate.
AB  - Archaea have been shown to produce isoprenoids from mevalonate; however, genome
      analysis has failed to identify several genes in the mevalonate pathway on the
      basis of sequence similarity. A predicted archaeal kinase, coded for by the
      MJ0044 gene, was associated with other mevalonate pathway genes in the archaea
      and was predicted to be the "missing" phosphomevalonate kinase. The MJ0044
      derived protein was tested for phosphomevalonate kinase activity and was found
      not to catalyze this reaction. The MJ0044 gene product was found to phosphorylate
      isopentenyl phosphate, generating isopentenyl diphosphate. Unlike other known
      kinases associated with isoprene biosynthesis, Methanocaldococcus jannaschii
      isopentenyl phosphate kinase is predicted to be a member of the aspartokinase
      superfamily.

PMID- 16621812
TI  - Mutational analysis of the Escherichia coli melR gene suggests a two-state
      concerted model to explain transcriptional activation and repression in the
      melibiose operon.
AB  - Transcription of the Escherichia coli melAB operon is regulated by the MelR
      protein, an AraC family member whose activity is modulated by the binding of
      melibiose. In the absence of melibiose, MelR is unable to activate the melAB
      promoter but autoregulates its own expression by repressing the melR promoter.
      Melibiose triggers MelR-dependent activation of the melAB promoter and relieves
      MelR-dependent repression of the melR promoter. Twenty-nine single amino acid
      substitutions in MelR that result in partial melibiose-independent activation of
      the melAB promoter have been identified. Combinations of different substitutions
      result in almost complete melibiose-independent activation of the melAB promoter.
      MelR carrying each of the single substitutions is less able to repress the melR
      promoter, while MelR carrying some combinations of substitutions is completely
      unable to repress the melR promoter. These results argue that different
      conformational states of MelR are responsible for activation of the melAB
      promoter and repression of the melR promoter. Supporting evidence for this is
      provided by the isolation of substitutions in MelR that block melibiose-dependent
      activation of the melAB promoter while not changing melibiose-independent
      repression of the melR promoter. Additional experiments with a bacterial two
      hybrid system suggest that interactions between MelR subunits differ according to
      the two conformational states.

PMID- 16621813
TI  - In vitro and in vivo analysis of the role of PrrA in Rhodobacter sphaeroides
      2.4.1 hemA gene expression.
AB  - The hemA gene codes for one of two synthases in Rhodobacter sphaeroides 2.4.1
      which catalyze the formation of 5-aminolevulinic acid. We have examined the role
      of PrrA, a DNA binding protein that is associated with the metabolic switch
      between aerobic growth and anoxygenic photosynthetic growth, in hemA expression
      and found that hemA transcription is directly activated by PrrA. Using
      electrophoretic mobility shift assays and DNase I protection assays, we have
      mapped two binding sites for PrrA within the hemA upstream sequences, each of
      which contains an identical 9-bp motif. Using lacZ transcription reporter
      plasmids in wild-type strain 2.4.1 and PrrA- mutant strain PRRA2, we showed that
      PrrA was required for maximal expression. We also found that the relative impacts
      of altering DNA sequences within the two binding sites are different depending on
      whether cells are growing aerobically or anaerobically. This reveals a greater
      level of complexity associated with PrrA-mediated regulation of transcription
      than has been heretofore described. Our findings are of particular importance
      with respect to those genes regulated by PrrA having more than one upstream
      binding site. In the case of the hemA gene, we discuss possibilities as to how
      these new insights can be accommodated within the context of what has already
      been established for hemA transcription regulation in R. sphaeroides.

PMID- 16621814
TI  - Thin aggregative fimbriae and cellulose enhance long-term survival and
      persistence of Salmonella.
AB  - Salmonella spp. are environmentally persistent pathogens that have served as one
      of the important models for understanding how bacteria adapt to stressful
      conditions. However, it remains poorly understood how they survive extreme
      conditions encountered outside their hosts. Here we show that the rdar
      morphotype, a multicellular phenotype characterized by fimbria- and cellulose
      mediated colony pattern formation, enhances the resistance of Salmonella to
      desiccation. When colonies were stored on plastic for several months in the
      absence of exogenous nutrients, survival of wild-type cells was increased
      compared to mutants deficient in fimbriae and/or cellulose production.
      Differences between strains were further highlighted upon exposure to sodium
      hypochlorite, as cellulose-deficient strains were 1,000-fold more susceptible.
      Measurements of gene expression using luciferase reporters indicated that
      production of thin aggregative fimbriae (Tafi) may initiate formation of colony
      surface patterns characteristic of the rdar morphotype. We hypothesize that Tafi
      play a role in the organization of different components of the extracellular
      matrix. Conservation of the rdar morphotype among pathogenic S. enterica isolates
      and the survival advantages that it provides collectively suggest that this
      phenotype could play a role in the transmission of Salmonella between hosts.

PMID- 16621815
TI  - Selenium is involved in regulation of periplasmic hydrogenase gene expression in
      Desulfovibrio vulgaris Hildenborough.
AB  - Desulfovibrio vulgaris Hildenborough is a good model organism to study hydrogen
      metabolism in sulfate-reducing bacteria. Hydrogen is a key compound for these
      organisms, since it is one of their major energy sources in natural habitats and
      also an intermediate in the energy metabolism. The D. vulgaris Hildenborough
      genome codes for six different hydrogenases, but only three of them, the
      periplasmic-facing [FeFe], [FeNi]1, and [FeNiSe] hydrogenases, are usually
      detected. In this work, we studied the synthesis of each of these enzymes in
      response to different electron donors and acceptors for growth as well as in
      response to the availability of Ni and Se. The formation of the three
      hydrogenases was not very strongly affected by the electron donors or acceptors
      used, but the highest levels were observed after growth with hydrogen as electron
      donor and lowest with thiosulfate as electron acceptor. The major effect observed
      was with inclusion of Se in the growth medium, which led to a strong repression
      of the [FeFe] and [NiFe]1 hydrogenases and a strong increase in the [NiFeSe]
      hydrogenase that is not detected in the absence of Se. Ni also led to increased
      formation of the [NiFe]1 hydrogenase, except for growth with H2, where its
      synthesis is very high even without Ni added to the medium. Growth with H2
      results in a strong increase in the soluble forms of the [NiFe]1 and [NiFeSe]
      hydrogenases. This study is an important contribution to understanding why D.
      vulgaris Hildenborough has three periplasmic hydrogenases. It supports their
      similar physiological role in H2 oxidation and reveals that element availability
      has a strong influence in their relative expression.

PMID- 16621816
TI  - Mutational analysis of intervening sequences connecting the binding sites for
      integration host factor, PepA, PurR, and RNA polymerase in the control region of
      the Escherichia coli carAB operon, encoding carbamoylphosphate synthase.
AB  - Transcription of the carAB operon encoding the unique carbamoylphosphate synthase
      of Escherichia coli reflects the dual function of carbamoylphosphate in the
      biosynthesis of arginine and pyrimidine nucleotides. The tandem pair of promoters
      is regulated by various mechanisms depending on the needs of both pathways and
      the maintenance of a pyrimidine/purine nucleotide balance. Here we focus on the
      linker regions that impose the distribution of target sites for DNA-binding
      proteins involved in pyrimidine- and purine-specific repression of the upstream
      promoter P1. We introduced deletions and insertions, and combinations thereof, in
      four linkers connecting the binding sites for integration host factor (IHF),
      PepA, PurR, and RNA polymerase and studied the importance of phasing and spacing
      of the targets and the importance of the nucleotide sequence of the linkers. The
      two PepA binding sites must be properly aligned and separated with respect to
      each other and to the promoter for both pyrimidine- and purine-mediated
      repression. Similarly, the phasing and spacing of the IHF and PEPA2 sites are
      strictly constrained but only for pyrimidine-specific repression. The IHF target
      is even dispensable for purine-mediated regulation. Thus, a correct localization
      of PepA within the higher-order nucleoprotein complex is a prerequisite for the
      establishment of pyrimidine-mediated repression and for the coupling between
      purine- and pyrimidine-dependent regulation. Our data also suggest the existence
      of a novel cis-acting pyrimidine-specific regulatory target located around
      position -60. Finally, the analysis of a P1 derivative devoid of its control
      region has led to a reappraisal of the effect of excess adenine on P1 and has
      revealed that P1 has no need for a UP element.

PMID- 16621817
TI  - Role of sigmaD in regulating genes and signals during Myxococcus xanthus
      development.
AB  - Starvation-induced development of Myxococcus xanthus is an excellent model for
      biofilm formation because it involves cell-cell signaling to coordinate formation
      of multicellular mounds, gene expression, and cellular differentiation into
      spores. The role of sigma(D), an alternative sigma factor important for viability
      in stationary phase and for stress responses, was investigated during development
      by measuring signal production, gene expression, and sporulation of a sigD null
      mutant alone and upon codevelopment with wild-type cells or signaling mutants.
      The sigD mutant responded to starvation by inducing (p)ppGpp synthesis normally
      but was impaired for production of A-signal, an early cell density signal, and
      for production of the morphogenetic C-signal. Induction of early developmental
      genes was greatly reduced, and expression of those that depend on A-signal was
      not restored by codevelopment with wild-type cells, indicating that sigma(D) is
      needed for cellular responses to A-signal. Despite these early developmental
      defects, the sigD mutant responded to C-signal supplied by codeveloping wild-type
      cells by inducing a subset of late developmental genes. sigma(D) RNA polymerase
      is dispensable for transcription of this subset, but a distinct regulatory class,
      which includes genes essential for sporulation, requires sigma(D) RNA polymerase
      or a gene under its control, cell autonomously. The level of sigD transcript in a
      relA mutant during growth is much lower than in wild-type cells, suggesting that
      (p)ppGpp positively regulates sigD transcription in growing cells. The sigD
      transcript level drops in wild-type cells after 20 min of starvation and remains
      low after 40 min but rises in a relA mutant after 40 min, suggesting that
      (p)ppGpp negatively regulates sigD transcription early in development. We
      conclude that sigma(D) synthesized during growth occupies a position near the top
      of a regulatory hierarchy governing M. xanthus development, analogous to sigma
      factors that control biofilm formation of other bacteria.

PMID- 16621818
TI  - Regulation of RraA, a protein inhibitor of RNase E-mediated RNA decay.
AB  - The recently discovered RraA protein acts as an inhibitor of the essential
      endoribonuclease RNase E, and we demonstrated that ectopic expression of RraA
      affects the abundance of more than 700 transcripts in Escherichia coli (K. Lee,
      X. Zhan, J. Gao, J. Qiu, Y. Feng, R. Meganathan, S. N. Cohen, and G. Georgiou,
      Cell 114:623-634, 2003). We show that rraA is expressed from its own promoter,
      P(rraA), located in the menA-rraA intergenic region. Primer extension and lacZ
      fusion analysis revealed that transcription from P(rraA) is elevated upon entry
      into stationary phase in a sigma(s)-dependent manner. In addition, the stability
      of the rraA transcript is dependent on RNase E activity, suggesting the
      involvement of a feedback circuit in the regulation of the RraA level in E. coli.

PMID- 16621819
TI  - Specific modification of a Na+ binding site in NADH:quinone oxidoreductase from
      Klebsiella pneumoniae with dicyclohexylcarbodiimide.
AB  - The respiratory NADH:quinone oxidoreductase (complex I) (NDH-1) is a multisubunit
      enzyme that translocates protons (or in some cases Na+) across energy-conserving
      membranes from bacteria or mitochondria. We studied the reaction of the Na+
      translocating complex I from the enterobacterium Klebsiella pneumoniae with N,N'
      dicyclohexylcarbodiimide (DCCD), with the aim of identifying a subunit critical
      for Na+ binding. At low Na+ concentrations (0.6 mM), DCCD inhibited both quinone
      reduction and Na+ transport by NDH-1 concurrent with the covalent modification of
      a 30-kDa polypeptide. In the presence of 50 mM Na+, NDH-1 was protected from
      inhibition by DCCD, and the modification of the 30-kDa polypeptide with [14C]DCCD
      was prevented, indicating that Na+ and DCCD competed for the binding to a
      critical carboxyl group in NDH-1. The 30-kDa polypeptide was assigned to NuoH,
      the homologue of the ND1 subunit from mitochondrial complex I. It is proposed
      that Na+ binds to the NuoH subunit during NADH-driven Na+ transport by NDH-1.

PMID- 16621820
TI  - Mutation of waaC, encoding heptosyltransferase I in Campylobacter jejuni 81-176,
      affects the structure of both lipooligosaccharide and capsular carbohydrate.
AB  - Campylobacter jejuni 81-176 lipooligosaccharide (LOS) is composed of two
      covalently linked domains: lipid A, a hydrophobic anchor, and a nonrepeating core
      oligosaccharide, consisting of an inner and outer core region. We report the
      isolation and characterization of the deepest rough C. jejuni 81-176 mutant by
      insertional mutagenesis into the waaC gene, encoding heptosyltransferase I that
      catalyzes the transfer of the first L-glycero-D-manno-heptose residue to 3-deoxy
      D-manno-octulosonic residue (Kdo)-lipid A. Tricine gel electrophoresis, followed
      by silver staining, showed that site-specific mutation in the waaC gene resulted
      in the expression of a severely truncated LOS compared to wild-type strain 81
      176. Gas-liquid chromatography-mass spectrometry and nuclear magnetic resonance
      spectroscopy showed that the waaC LOS species lacked all sugars distal to Kdo
      lipid A. Parallel structural studies of the capsular polysaccharides of the wild
      type strain 81-176 and waaC mutant revealed loss of the 3-O-methyl group in the
      waaC mutant. Complementation of the C. jejuni mutant by insertion of the wild
      type C. jejuni waaC gene into a chromosomal locus resulted in LOS and capsular
      structures identical to those expressed in the parent strain. We also report here
      the presence of O-methyl phosphoramidate in wild-type strain 81-176 capsular
      polysaccharide.

PMID- 16621821
TI  - Identification and functional characterization of the Lactococcus lactis CodY
      regulated branched-chain amino acid permease BcaP (CtrA).
AB  - Transcriptome analyses have previously revealed that a gene encoding the putative
      amino acid transporter CtrA (YhdG) is one of the major targets of the pleiotropic
      regulator CodY in Lactococcus lactis and Bacillus subtilis. The role of ctrA in
      L. lactis was further investigated with respect to both transport activity as
      well as CodY-mediated regulation. CtrA is required for optimal growth in media
      containing free amino acids as the only amino acid source. Amino acid transport
      studies showed that ctrA encodes a secondary amino acid transport system that is
      specific for branched-chain amino acids (BCAAs) (isoleucine, leucine, and valine)
      and methionine, which is in disagreement with its previously proposed function (a
      cationic amino acid transporter), which was assigned based on homology. We
      propose to rename CtrA BcaP, for branched-chain amino acid permease. BcaP is a
      member of a group of conserved transport systems, as homologs are widely
      distributed among gram-positive bacteria. Deletion of bcaP resulted in the loss
      of most of the BCAA uptake activity of L. lactis, indicating that BcaP is the
      major BCAA carrier of this organism. Deletion of bcaP together with a second
      (putative) BCAA permease, encoded by brnQ, further reduced the viability of the
      strain. DNA microarray analysis showed that deletion of bcaP predominantly
      affects genes belonging to the regulons of the transcriptional regulator CodY,
      which is involved in global nitrogen metabolism and needs BCAAs for its
      activation, and of CmbR, which is involved in sulfur amino acid metabolism.

PMID- 16621822
TI  - Characterization of the transcriptional activators SalA and SyrF, Which are
      required for syringomycin and syringopeptin production by Pseudomonas syringae
      pv. syringae.
AB  - Production of the phytotoxins syringomycin and syringopeptin by Pseudomonas
      syringae pv. syringae is controlled by the regulatory genes salA and syrF.
      Analysis with 70-mer oligonucleotide microarrays established that the syr-syp
      genes responsible for synthesis and secretion of syringomycin and syringopeptin
      belong to the SyrF regulon. Vector pMEKm12 was successfully used to express both
      SalA and SyrF proteins fused to a maltose-binding protein (MBP) in Escherichia
      coli and P. syringae pv. syringae. Both the MBP-SalA and MBP-SyrF fusion proteins
      were purified by maltose affinity chromatography. Gel shift analysis revealed
      that the purified MBP-SyrF, but not the MBP-SalA fusion protein, bound to a 262
      bp fragment of the syrB1 promoter region containing the syr-syp box. Purified MBP
      SalA caused a shift of a 324-bp band containing the putative syrF promoter. Gel
      filtration analysis and cross-linking experiments indicated that both SalA and
      SyrF form homodimers in vitro. Overexpression of the N-terminal regions of SalA
      and SyrF resulted in decreased syringomycin production by strain B301D and
      reduced levels of beta-glucuronidase activities of the sypA::uidA and syrB1::uidA
      reporters by 59% to 74%. The effect of SalA on the expression of the syr-syp
      genes is mediated by SyrF, which activates the syr-syp genes by directly binding
      to the promoter regions. Both SalA and SyrF resemble other LuxR family proteins
      in dimerization and interaction with promoter regions of target genes.

PMID- 16621823
TI  - Mutational analysis of the chemoreceptor-coupling domain of the Escherichia coli
      chemotaxis signaling kinase CheA.
AB  - During chemotactic signaling by Escherichia coli, autophosphorylation of the
      histidine kinase CheA is coupled to chemoreceptor control by the CheW protein,
      which interacts with the C-terminal P5 domain of CheA. To identify P5
      determinants important for CheW binding and receptor coupling control, we
      isolated and characterized a series of P5 missense mutants. The mutants fell into
      four phenotypic groups on the basis of in vivo behavioral and protein stability
      tests and in vitro assays with purified mutant proteins. Group 1 mutants
      exhibited autophosphorylation and receptor-coupling defects, and their CheA
      proteins were subject to relatively rapid degradation in vivo. Group 1 mutations
      were located at hydrophobic residues in P5 subdomain 2 and most likely caused
      folding defects. Group 2 mutants made stable CheA proteins with normal
      autophosphorylation ability but with defects in CheW binding and in receptor
      mediated activation of CheA autophosphorylation. Their mutations affected
      residues in P5 subdomain 1 near the interface with the CheA dimerization (P3) and
      ATP-binding (P4) domains. Mutant proteins of group 3 were normal in all tests yet
      could not support chemotaxis, suggesting that P5 has one or more important but
      still unknown signaling functions. Group 4 mutant proteins were specifically
      defective in receptor-mediated deactivation control. The group 4 mutations were
      located in P5 subdomain 1 at the P3/P3' interface. We conclude that P5 subdomain
      1 is important for CheW binding and for receptor coupling control and that these
      processes may require substantial motions of the P5 domain relative to the
      neighboring P3 and P4 domains of CheA.

PMID- 16621824
TI  - Posttranscriptional control of the Salmonella enterica flagellar hook protein
      FlgE.
AB  - Previous work suggested that the FlgE (flagellar hook subunit) protein in
      Salmonella enterica serovar Typhimurium was posttranscriptionally regulated in
      response to the stage of flagellar assembly. Specifically, the FlgE protein could
      be detected in flagellar mutants defective at the stages of assembly before or
      after rod assembly but not in rod assembly mutants, yet flgE mRNA levels were
      unaffected. To elucidate posttranscriptional mechanisms involved in the coupling
      of flgE gene expression to hook assembly, the RNA sequences at the 5' and 3' ends
      of the flgE-containing mRNA processed from the large flgBCDEFGHIJKL operon were
      determined by rapid amplification of cDNA ends, and secretion of the FlgE protein
      in different flagellar assembly mutant strains was analyzed. The sequences 5' and
      3' of the flgE gene where RNA processing occurred was within 15 bases upstream of
      the flgD stop codon and at bases 145 to 147 downstream of the flgF start codon,
      respectively. The ribosome binding site of the flgD gene was found to be
      inhibitory to flgE translation in strains deleted for the upstream flgD gene,
      unless the region 15 bases upstream of the flgD stop codon was present. Secretion
      of FlgE into the periplasm was monitored using beta-lactamase (Bla) fusions as a
      periplasm-specific reporter, which conferred resistance to ampicillin when FlgE
      Bla was secreted into the periplasm. Using this assay, we found that the effect
      of rod assembly mutants on FlgE levels was due to FlgE turnover in the periplasm
      and that the FliE rod component protein was required for efficient FlgE-Bla
      secretion.

PMID- 16621825
TI  - Pyoverdine-mediated iron uptake in Pseudomonas aeruginosa: the Tat system is
      required for PvdN but not for FpvA transport.
AB  - Under iron-limiting conditions, Pseudomonas aeruginosa PAO1 secretes a
      fluorescent siderophore called pyoverdine (Pvd). After chelating iron, this
      ferric siderophore is transported back into the cells via the outer membrane
      receptor FpvA. The Pvd-dependent iron uptake pathway requires several essential
      genes involved in both the synthesis of Pvd and the uptake of ferric Pvd inside
      the cell. A previous study describing the global phenotype of a tat-deficient P.
      aeruginosa strain showed that the defect in Pvd-mediated iron uptake was due to
      the Tat-dependent export of proteins involved in Pvd biogenesis and ferric Pvd
      uptake (U. Ochsner, A. Snyder, A. I. Vasil, and M. L. Vasil, Proc. Natl. Acad.
      Sci. USA 99:8312-8317, 2002). Using biochemical and biophysical tools, we showed
      that despite its predicted Tat signal sequence, FpvA is correctly located in the
      outer membrane of a tat mutant and is fully functional for all steps of the iron
      uptake process (ferric Pvd uptake and recycling of Pvd on FpvA after iron
      release). However, in the tat mutant, no Pvd was produced. This suggested that a
      key element in the Pvd biogenesis pathway must be exported to the periplasm by
      the Tat pathway. We located PvdN, a still unknown but essential component in Pvd
      biogenesis, at the periplasmic side of the cytoplasmic membrane and showed that
      its export is Tat dependent. Our results further support the idea that a critical
      step of the Pvd biogenesis pathway involving PvdN occurs at the periplasmic side
      of the cytoplasmic membrane.

PMID- 16621826
TI  - Microcin J25 uptake: His5 of the MccJ25 lariat ring is involved in interaction
      with the inner membrane MccJ25 transporter protein SbmA.
AB  - Escherichia coli microcin J25 (MccJ25) is a plasmid-encoded antibiotic peptide
      consisting of 21 L-amino acid residues (G1-G-A-G-H5-V-P-E-Y-F10-V-G-I-G-T15-P-I-S
      F-Y20-G). E. coli RNA polymerase (RNAP) is the intracellular target of MccJ25.
      MccJ25 enters cells after binding to specific membrane transporters: FhuA in the
      outer membrane and SbmA in the inner membrane. Here, we studied MccJ25 mutants
      carrying a substitution of His5 by Lys, Arg, or Ala. The inhibitory effects on
      cellular growth and in vitro RNAP activity were determined for each mutant
      microcin. The results show that all mutants inhibited RNAP in vitro. However, the
      mutants were defective in their ability to inhibit cellular growth. Experiments
      in which the FhuA protein was bypassed showed that substitutions of MccJ25 His5
      affected the SbmA-dependent transport. Our results thus suggest that MccJ25 His5
      located in the lariat ring is involved, directly or indirectly, in specific
      interaction with SbmA and is not required for MccJ25 inhibition of RNAP.

PMID- 16621827
TI  - The hydantoin transport protein from Microbacterium liquefaciens.
AB  - The gene hyuP from Microbacterium liquefaciens AJ 3912 with an added His6 tag was
      cloned into the expression plasmid pTTQ18 in an Escherichia coli host strain. The
      transformed E. coli showed transport of radioisotope-labeled 5-substituted
      hydantoins with apparent K(m) values in the micromolar range. This activity
      exhibited a pH optimum of 6.6 and was inhibited by dinitrophenol, indicating the
      requirement of energy for the transport system. 5-Indolyl methyl hydantoin and 5
      benzyl hydantoin were the preferred substrates, with selectivity for a
      hydrophobic substituent in position 5 of hydantoin and for the l isomer over the
      d isomer. Hydantoins with less hydrophobic substituents, cytosine, thiamine,
      uracil, allantoin, adenine, and guanine, were not effective ligands. The His
      tagged hydantoin transport protein was located in the inner membrane fraction,
      from which it was solubilized and purified and its identity was authenticated.

PMID- 16621828
TI  - Sll0254 (CrtL(diox)) is a bifunctional lycopene cyclase/dioxygenase in
      cyanobacteria producing myxoxanthophyll.
AB  - Upon depletion of Sll0254 in Synechocystis sp. strain PCC 6803, cyclized
      carotenoids were replaced by linear, relatively hydrophilic carotenoids, and the
      amount of the two photosystems decreased greatly. Full segregants of the sll0254
      deletion in Synechocystis were not obtained, implying that this gene is essential
      for survival, most likely to allow normal cell division. The N-terminal half of
      Sll0254 has limited similarity to the family of lycopene cyclases, has an
      additional dehydrogenase motif near the N terminus, and is followed by a Rieske
      2Fe-2S center sequence signature. To test whether Sll0254 serves as a lycopene
      cyclase in Synechocystis, the corresponding gene was expressed in Escherichia
      coli strains that can produce lycopene or neurosporene. In the presence of
      Sll0254 these linear carotenoids were converted into cyclized, relatively
      hydrophilic pigments, with masses consistent with the introduction of two
      hydroxyl groups and with spectra indicative of only small changes in the number
      of conjugated double bonds. This suggests that Sll0254 catalyzes formation of
      oxygenated, cyclized carotenoids. We interpret the appearance of the hydroxyl
      groups in the carotenoids to be due to dioxygenase activity involving the Rieske
      2Fe-2S center and the additional dehydrogenase domain. This dioxygenase activity
      is required in the myxoxanthophyll biosynthesis pathway, after or concomitant
      with cyclization on the other end of the molecule. We interpret Sll0254 to be a
      dual-function enzyme with both lycopene cyclase and dioxygenase activity and have
      named it CrtL(diox).

PMID- 16621829
TI  - Biochemical bases of type IV chromatic adaptation in marine Synechococcus spp.
AB  - Chromatic adaptation (CA) in cyanobacteria has provided a model system for the
      study of the environmental control of photophysiology for several decades. All
      forms of CA that have been examined so far (types II and III) involve changes in
      the relative contents of phycoerythrin (PE) and/or phycocyanin when cells are
      shifted from red to green light and vice versa. However, the chromophore
      compositions of these polypeptides are not altered. Some marine Synechococcus
      species strains, which possess two PE forms (PEI and PEII), carry out another
      type of CA (type IV), occurring during shifts from blue to green or white light.
      Two chromatically adapting strains of marine Synechococcus recently isolated from
      the Gulf of Mexico were utilized to elucidate the mechanism of type IV CA. During
      this process, no change in the relative contents of PEI and PEII was observed.
      Instead, the ratio of the two chromophores bound to PEII, phycourobilin and
      phycoerythrobilin, is high under blue light and low under white light. Mass
      spectroscopy analyses of isolated PEII alpha- and beta-subunits show that there
      is a single PEII protein type under all light climates. The CA process seems to
      specifically affect the chromophorylation of the PEII (and possibly PEI) alpha
      chain. We propose a likely process for type IV CA, which involves the enzymatic
      activity of one or several phycobilin lyases and/or lyase-isomerases
      differentially controlled by the ambient light quality. Phylogenetic analyses
      based on the 16S rRNA gene confirm that type IV CA is not limited to a single
      clade of marine Synechococcus.

PMID- 16621830
TI  - Heme and a five-amino-acid hemophore region form the bipartite stimulus
      triggering the has signaling cascade.
AB  - Bacterial cells sense the extracellular environment and adapt to that environment
      by activating gene regulation circuits, often by means of signaling molecules.
      The Serratia marcescens hemophore is a signaling molecule that acts as an
      extracellular heme-scavenging protein. The heme-loaded hemophore interacts with
      its cognate receptor (HasR), triggering transmembrane signaling and turning on
      transcription of hemophore-dependent heme uptake genes. We investigated the
      features of the holo-hemophore, the only HasR ligand known to act as an inducer.
      We used a hemophore mutant that does not deliver its heme and a HasR mutant that
      does not bind heme, and we showed that heme transfer from the hemophore to the
      receptor is necessary for induction. Using a hemophore mutant that does not bind
      heme and that blocks heme transport, we demonstrated that two molecules that do
      not interact (heme and the mutant hemophore) may nonetheless induce this system.
      These findings suggest that hemophore-mediated induction and heme transport
      involve different mechanisms. The hemophore region important for induction was
      precisely localized to amino acids 50 to 55, which lie in one of the two HasR
      binding hemophore regions. This bipartite stimulus probably corresponds to a
      physiological process because heme is transferred to the receptor before apo
      hemophore release. This bipartite regulation mechanism may allow the bacterium to
      adjust its heme transport mechanism to the perceived environmental heme
      concentration.

PMID- 16621831
TI  - A distinct QscR regulon in the Pseudomonas aeruginosa quorum-sensing circuit.
AB  - The opportunistic pathogen Pseudomonas aeruginosa possesses two complete acyl
      homoserine lactone (acyl-HSL) signaling systems. One system consists of LasI and
      LasR, which generate a 3-oxododecanoyl-homoserine lactone signal and respond to
      that signal, respectively. The other system is RhlI and RhlR, which generate
      butanoyl-homoserine lactone and respond to butanoyl-homoserine lactone,
      respectively. These quorum-sensing systems control hundreds of genes. There is
      also an orphan LasR-RhlR homolog, QscR, for which there is no cognate acyl-HSL
      synthetic enzyme. We previously reported that a qscR mutant is hypervirulent and
      showed that QscR transiently represses a few quorum-sensing-controlled genes. To
      better understand the role of QscR in P. aeruginosa gene regulation and to better
      understand the relationship between QscR, LasR, and RhlR control of gene
      expression, we used transcription profiling to identify a QscR-dependent regulon.
      Our analysis revealed that QscR activates some genes and represses others. Some
      of the repressed genes are not regulated by the LasR-I or RhlR-I systems, while
      others are. The LasI-generated 3-oxododecanoyl-homoserine lactone serves as a
      signal molecule for QscR. Thus, QscR appears to be an integral component of the
      P. aeruginosa quorum-sensing circuitry. QscR uses the LasI-generated acyl
      homoserine lactone signal and controls a specific regulon that overlaps with the
      already overlapping LasR- and RhlR-dependent regulons.

PMID- 16621832
TI  - Effect of chromate stress on Escherichia coli K-12.
AB  - The nature of the stress experienced by Escherichia coli K-12 exposed to
      chromate, and mechanisms that may enable cells to withstand this stress, were
      examined. Cells that had been preadapted by overnight growth in the presence of
      chromate were less stressed than nonadapted controls. Within 3 h of chromate
      exposure, the latter ceased growth and exhibited extreme filamentous morphology;
      by 5 h there was partial recovery with restoration of relatively normal cell
      morphology. In contrast, preadapted cells were less drastically affected in their
      morphology and growth. Cellular oxidative stress, as monitored by use of an H2O2
      responsive fluorescent dye, was most severe in the nonadapted cells at 3 h
      postinoculation, lower in the partially recovered cells at 5 h postinoculation,
      and lower still in the preadapted cells. Chromate exposure depleted cellular
      levels of reduced glutathione and other free thiols to a greater extent in
      nonadapted than preadapted cells. In both cell types, the SOS response was
      activated, and levels of proteins such as SodB and CysK, which can counter
      oxidative stress, were increased. Some mutants missing antioxidant proteins
      (SodB, CysK, YieF, or KatE) were more sensitive to chromate. Thus, oxidative
      stress plays a major role in chromate toxicity in vivo, and cellular defense
      against this toxicity involves activation of antioxidant mechanisms. As bacterial
      chromate bioremediation is limited by the toxicity of chromate, minimizing
      oxidative stress during bacterial chromate reduction and bolstering the capacity
      of these organisms to deal with this stress will improve their effectiveness in
      chromate bioremediation.

PMID- 16621833
TI  - Pathogenomic sequence analysis of Bacillus cereus and Bacillus thuringiensis
      isolates closely related to Bacillus anthracis.
AB  - Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are closely
      related gram-positive, spore-forming bacteria of the B. cereus sensu lato group.
      While independently derived strains of B. anthracis reveal conspicuous sequence
      homogeneity, environmental isolates of B. cereus and B. thuringiensis exhibit
      extensive genetic diversity. Here we report the sequencing and comparative
      analysis of the genomes of two members of the B. cereus group, B. thuringiensis
      97-27 subsp. konkukian serotype H34, isolated from a necrotic human wound, and B.
      cereus E33L, which was isolated from a swab of a zebra carcass in Namibia. These
      two strains, when analyzed by amplified fragment length polymorphism within a
      collection of over 300 of B. cereus, B. thuringiensis, and B. anthracis isolates,
      appear closely related to B. anthracis. The B. cereus E33L isolate appears to be
      the nearest relative to B. anthracis identified thus far. Whole-genome sequencing
      of B. thuringiensis 97-27and B. cereus E33L was undertaken to identify shared and
      unique genes among these isolates in comparison to the genomes of pathogenic
      strains B. anthracis Ames and B. cereus G9241 and nonpathogenic strains B. cereus
      ATCC 10987 and B. cereus ATCC 14579. Comparison of these genomes revealed
      differences in terms of virulence, metabolic competence, structural components,
      and regulatory mechanisms.

PMID- 16621835
TI  - Sequencing Bacillus anthracis typing phages gamma and cherry reveals a common
      ancestry.
AB  - The genetic relatedness of the Bacillus anthracis typing phages Gamma and Cherry
      was determined by nucleotide sequencing and comparative analysis. The genomes of
      these two phages were identical except at three variable loci, which showed
      heterogeneity within individual lysates and among Cherry, Wbeta, Fah, and four
      Gamma bacteriophage sequences.

PMID- 16621834
TI  - Structure of the functional form of the mosquito larvicidal Cry4Aa toxin from
      Bacillus thuringiensis at a 2.8-angstrom resolution.
AB  - The Cry4Aa delta-endotoxin from Bacillus thuringiensis is toxic to larvae of
      Culex, Anopheles, and Aedes mosquitoes, which are vectors of important human
      tropical diseases. With the objective of designing modified toxins with improved
      potency that could be used as biopesticides, we determined the structure of this
      toxin in its functional form at a resolution of 2.8 angstroms. Like other Cry
      delta-endotoxins, the activated Cry4Aa toxin consists of three globular domains,
      a seven-alpha-helix bundle responsible for pore formation (domain I) and the
      following two other domains having structural similarities with carbohydrate
      binding proteins: a beta-prism (domain II) and a plant lectin-like beta-sandwich
      (domain III). We also studied the effect on toxicity of amino acid substitutions
      and deletions in three loops located at the surface of the putative receptor
      binding domain II of Cry4Aa. Our results indicate that one loop is an important
      determinant of toxicity, presumably through attachment of Cry4Aa to the surface
      of mosquito cells. The availability of the Cry4Aa structure should guide further
      investigations aimed at the molecular basis of the target specificity and
      membrane insertion of Cry endotoxins.

PMID- 16621836
TI  - Role of secondary attachment sites in changing the specificity of site-specific
      recombination.
AB  - We previously proposed that lambdoid phages change their insertion specificity by
      adapting their integrases to sequences found in secondary attachment sites. To
      test this model, we quantified recombination between partners that carried
      sequences from secondary attachment sites catalyzed by wild-type and by mutant
      integrases with altered specificities. The results are consistent with the model,
      and indicate differential core site usage in excision and integration.

PMID- 16621837
TI  - Protein splicing of SufB is crucial for the functionality of the Mycobacterium
      tuberculosis SUF machinery.
AB  - The SufBCD complex is an essential component of the SUF machinery of [Fe-S]
      cluster biogenesis in many organisms. We show here that in Mycobacterium
      tuberculosis the formation of this complex is dependent on the protein splicing
      of SufB, suggesting that this process is a potential new target for
      antituberculous drugs.

PMID- 16621838
TI  - Functional characterization of Escherichia coli GlpG and additional rhomboid
      proteins using an aarA mutant of Providencia stuartii.
AB  - The Providencia stuartii AarA protein is a member of the rhomboid family of
      intramembrane serine proteases and required for the production of an
      extracellular signaling molecule that regulates cellular functions including
      peptidoglycan acetylation, methionine transport, and cysteine biosynthesis.
      Additional aarA-dependent phenotypes include (i) loss of an extracellular yellow
      pigment, (ii) inability to grow on MacConkey agar, and (iii) abnormal cell
      division. Since these phenotypes are easily assayed, the P. stuartii aarA mutant
      serves as a useful host system to investigate rhomboid function. The Escherichia
      coli GlpG protein was shown to be functionally similar to AarA and rescued the
      above aarA-dependent phenotypes in P. stuartii. GlpG proteins containing single
      alanine substitutions at the highly conserved catalytic triad of asparagine
      (N154A), serine (S201A), or histidine (H254A) residues were nonfunctional. The P.
      stuartii aarA mutant was also used as a biosensor to demonstrate that proteins
      from a variety of diverse sources exhibited rhomboid activity. In an effort to
      further investigate the role of a rhomboid protein in cell physiology, a glpG
      mutant of E. coli was constructed. In phenotype microarray experiments, the glpG
      mutant exhibited a slight increase in resistance to the beta-lactam antibiotic
      cefotaxime.

PMID- 16621839
TI  - Induction of Escherichia coli chromosomal mazEF by stressful conditions causes an
      irreversible loss of viability.
AB  - mazEF is a stress-induced toxin-antitoxin module located on the chromosomes of
      many bacteria. Here we induced Escherichia coli chromosomal mazEF by various
      stressful conditions. We found an irreversible loss of viability, which is the
      basic characteristic of cell death. These results further support our previous
      conclusion that E. coli mazEF mediation of cell death is not a passive process,
      but an active and genetically "programmed" death response.

PMID- 16621841
TI  - Borrelia burgdorferi ftsZ plays a role in cell division.

PMID- 16621840
TI  - Positive selection acting on a surface membrane protein of the plant-pathogenic
      phytoplasmas.
AB  - Phytoplasmas are plant-pathogenic bacteria that cause numerous diseases. This
      study shows a strong positive selection on the phytoplasma antigenic membrane
      protein (Amp). The ratio of nonsynonymous to synonymous substitutions was >1 with
      all the methods we tested. The clear positive selections imply an important
      biological role for Amp in host-bacterium interactions.

PMID- 16621842
TI  - The fern Adiantum capillus-veneris lacks stomatal responses to blue light.
AB  - We investigated the responses of stomata to light in the fern Adiantum capillus
      veneris, a typical species of Leptosporangiopsida. Stomata in the intact leaves
      of the sporophytes opened in response to red light, but they did not open when
      blue light was superimposed on the red light. The results were confirmed in the
      isolated Adiantum epidermis. The red light-induced stomatal response was not
      affected by the mutation of phy3, a chimeric protein of phytochrome and
      phototropin in this fern. The lack of a blue light-specific stomatal response was
      observed in three other fern species of Leptosporangiopsida, i.e. Pteris cretica,
      Asplenium scolopendrium and Nephrolepis auriculata. Fusicoccin, an activator of
      the plasma membrane H(+)-ATPase, induced both stomatal opening and H(+) release
      in the Adiantum epidermis. Adiantum phototropin genes AcPHOT1 and AcPHOT2 were
      expressed in the fern guard cells. The transformation of an Arabidopsis phot1
      phot2 double mutant, which lost blue light-specific stomatal opening, with
      AcPHOT1 restored the stomatal response to blue light. Taken together, these
      results suggest that ferns of Leptosporangiopsida lack a blue light-specific
      stomatal response, although the functional phototropin and plasma membrane H(+)
      ATPase are present in this species.

PMID- 16621843
TI  - Mutations in a putative chloride efflux transporter gene suppress the chloride
      requirement of photosystem II in the cytochrome c550-deficient mutant.
AB  - The cytochrome c550-deficient mutant (psbV-disruptant) of Synechocystis requires
      a high concentration of Cl(-) in the culture medium to support photosynthetic
      oxygen evolution. From this disruptant, we isolated spontaneous suppressor
      mutants that are able to grow photoautotrophically in the absence of Cl(-). Three
      independent mutations were identified: one was a deletion in slr0753 and two were
      a transposition of related insertion sequences in the same slr0753. The deduced
      product of slr0753 belongs to a novel group of the superfamily of ion efflux
      pumps and ion transporters. These results suggest that Slr0753 exports Cl(-) or a
      related anion, which is essential for PSII oxygen evolution.

PMID- 16621844
TI  - A mutation in At-nMat1a, which encodes a nuclear gene having high similarity to
      group II intron maturase, causes impaired splicing of mitochondrial NAD4
      transcript and altered carbon metabolism in Arabidopsis thaliana.
AB  - To elucidate the mechanism of cellulose synthesis, we isolated a mutant of
      Arabidopsis (changed sensitivity to cellulose synthesis inhibitors 1, css1) that
      showed changed sensitivity to cellulose biosynthesis inhibitor. The analysis of
      phenotypes indicated that the css1 mutation influenced various fundamental
      metabolic pathways including amino acid metabolism, triacylglycerol degradation
      and polysaccharide synthesis (cellulose and starch) during the early stage of
      plant growth. Unexpectedly, the map-based cloning of the gene responsible for the
      css1 mutation identified a protein (At-nMat1a) that was assumed to be a splicing
      factor of the mitochondrial group II intron. In accordance with this result, this
      mutant exhibited improper splicing of the mitochondrial NAD4 transcript. We
      noticed that the phenotypes of the css1 mutant are similar to the responses to
      anoxia that hinders mitochondrial aerobic respiration. It seems that the defect
      in the function of mitochondria influences various aspects of fundamental
      cellular metabolism including cellulose synthesis. Our results suggested that
      sucrose synthase (SuSy), an enzyme involved in the biosynthesis of cellulose,
      plays key roles in the connection between mitochondria and cellulose synthesis.
      The isolation of the css1 mutant also provides a useful resource in the study of
      post-transcriptional gene regulation in mitochondria.

PMID- 16621845
TI  - Polycations globally enhance binding of 14-3-3omega to target proteins in spinach
      leaves.
AB  - The binding of 14-3-3omega to phosphorylated nitrate reductase (pNR) is
      stimulated by cations such as Mg(2+) or spermine, and decreased by 5'-AMP. In
      order to determine whether binding to other cellular proteins is affected
      similarly, far-Western overlays of extracts prepared from light- or dark-treated
      spinach (Spinacia oleracea) leaves were performed using digoxigenin (DIG)-labeled
      Arabidopsis 14-3-3omega. When separated by SDS-PAGE, approximately 25 proteins of
      >35 kDa could be resolved that interacted with DIG-labeled 14-3-3omega in the
      absence of added cations. The presence of 5 mM Mg(2+) or 0.5 mM spermine enhanced
      binding to most of the target proteins to a maximum of about a doubling of the
      observed binding. In most cases, the binding was dependent on phosphorylation of
      the target protein, whereas that was not necessarily the case for binding to
      target proteins that were unaffected by polycations. The extent of stimulation
      varied among the target proteins, but there was no indication that the nature of
      the cation activator (e.g. Mg(2+) vs. spermine(4+)) altered the specificity for
      target proteins. In addition, binding of DIG-labeled 14-3-3omega to some, but not
      all, target proteins was reduced by 5 mM 5'-AMP. Interestingly, light/dark
      treatment of spinach leaves affected the subsequent binding of DIG-labeled 14-3
      3omega in the overlay assay to only a few of the target proteins, one of which
      was identified as NADH:nitrate reductase. Overall, the results suggest that the
      binding of 14-3-3s to targets in addition to pNR may also be regulated by
      polycations and 5'-AMP.

PMID- 16621846
TI  - Expression profiling of auxin-treated Arabidopsis roots: toward a molecular
      analysis of lateral root emergence.
AB  - Treating Arabidopsis roots with exogenous auxin results in dramatic changes in
      cellular processes including de novo induction of lateral roots which later
      emerge through the overlying cells. Microarray experiments reveal approximately
      80 genes that are substantially up-regulated in the root over the first 12 h
      following auxin treatment. We hypothesize that the observed increase in
      expression of pectate lyase family genes leads to degradation of the pectin-rich
      middle lamellae, allowing cells in the parent root to separate cleanly.
      Differences in the degree of pectin methylation in lateral and parent roots may
      explain why lateral roots are not degraded themselves.

PMID- 16621847
TI  - Intervention trials on upper body pain among computer operators.

PMID- 16621848
TI  - Health risks from mobile phone base stations.

PMID- 16621849
TI  - A randomised controlled trial evaluating the effects of two workstation
      interventions on upper body pain and incident musculoskeletal disorders among
      computer operators.
AB  - BACKGROUND: Call centre work with computers is associated with increased rates of
      upper body pain and musculoskeletal disorders. METHODS: This one year, randomised
      controlled intervention trial evaluated the effects of a wide forearm support
      surface and a trackball on upper body pain severity and incident musculoskeletal
      disorders among 182 call centre operators at a large healthcare company.
      Participants were randomised to receive (1) ergonomics training only, (2)
      training plus a trackball, (3) training plus a forearm support, or (4) training
      plus a trackball and forearm support. Outcome measures were weekly pain severity
      scores and diagnosis of incident musculoskeletal disorder in the upper
      extremities or the neck/shoulder region based on physical examination performed
      by a physician blinded to intervention. Analyses using Cox proportional hazard
      models and linear regression models adjusted for demographic factors, baseline
      pain levels, and psychosocial job factors. RESULTS: Post-intervention, 63
      participants were diagnosed with one or more incident musculoskeletal disorders.
      Hazard rate ratios showed a protective effect of the armboard for neck/shoulder
      disorders (HR = 0.49, 95% CI 0.24 to 0.97) after adjusting for baseline pain
      levels and demographic and psychosocial factors. The armboard also significantly
      reduced neck/shoulder pain (p = 0.01) and right upper extremity pain (p = 0.002)
      in comparison to the control group. A return-on-investment model predicted a full
      return of armboard and installation costs within 10.6 months. CONCLUSION:
      Providing a large forearm support combined with ergonomic training is an
      effective intervention to prevent upper body musculoskeletal disorders and reduce
      upper body pain associated with computer work among call centre employees.

PMID- 16621850
TI  - Subjective symptoms, sleeping problems, and cognitive performance in subjects
      living near mobile phone base stations.
AB  - BACKGROUND: The erection of mobile telephone base stations in inhabited areas has
      raised concerns about possible health effects caused by emitted microwaves.
      METHODS: In a cross-sectional study of randomly selected inhabitants living in
      urban and rural areas for more than one year near to 10 selected base stations,
      365 subjects were investigated. Several cognitive tests were performed, and
      wellbeing and sleep quality were assessed. Field strength of high-frequency
      electromagnetic fields (HF-EMF) was measured in the bedrooms of 336 households.
      RESULTS: Total HF-EMF and exposure related to mobile telecommunication were far
      below recommended levels (max. 4.1 mW/m2). Distance from antennae was 24-600 m in
      the rural area and 20-250 m in the urban area. Average power density was slightly
      higher in the rural area (0.05 mW/m2) than in the urban area (0.02 mW/m2).
      Despite the influence of confounding variables, including fear of adverse effects
      from exposure to HF-EMF from the base station, there was a significant relation
      of some symptoms to measured power density; this was highest for headaches.
      Perceptual speed increased, while accuracy decreased insignificantly with
      increasing exposure levels. There was no significant effect on sleep quality.
      CONCLUSION: Despite very low exposure to HF-EMF, effects on wellbeing and
      performance cannot be ruled out, as shown by recently obtained experimental
      results; however, mechanisms of action at these low levels are unknown.

PMID- 16621851
TI  - Risk of affective and stress related disorders among employees in human service
      professions.
AB  - OBJECTIVES: To examine the risk of affective and stress related disorders among
      men and women employed in human service professions. METHODS: Population based
      case-control study using data from national registers. Cases (n = 28 971) were
      identified in the Danish Psychiatric Central Research Register among all
      hospitalised patients and outpatients aged 18-65 who received a first time ever
      diagnosis of affective (ICD-10, F30-39) or stress related (ICD-10, F40-48)
      disorder from 1 January 1995 to 31 December 1998. Each case was assigned five
      never admitted referents (n = 144 855) of the same gender and age, randomly drawn
      from a 5% sample of the Danish population obtained from Statistics Denmark's
      Integrated Database for Labour Market Research. Occupation held the year before
      matching was classified according to the Danish version of the International
      Classification of Occupation. Health care, education, social work, and customer
      services were defined as human service professions and constituted 21% of all
      employed in the study. Adjusted risks (hazard ratios) relative to all other
      occupations were calculated for 24 human service occupations. RESULTS: The
      relative risk of depression in human service professions was 1.35 (95% CI 1.24 to
      1.47) for women and 1.49 (95% CI 1.29 to 1.73) for men. The risk of stress was
      1.18 (95% CI 1.11 to 1.26) for women and 1.49 (95% CI 1.32 to 1.67) for men.
      Specific professions contributed differentially to the magnitude of risk, with
      education and social services displaying the highest risks. No increase in risks
      was found in customer service occupations. Gender was a significant modifying
      factor with the highest risk levels in men. CONCLUSIONS: There was a consistent
      association between employment in human service occupations and the risk of
      affective and stress related disorders. Risks were highest for men working in
      these typically female professions. More work is needed to distinguish work
      hazards from effects attributable to selection mechanisms and personality
      characteristics.

PMID- 16621852
TI  - Dust related risks of clinically relevant lung functional deficits.
AB  - AIM: To quantify the risks of clinically important deficits of FEV1 in coal
      miners in relation to cumulative and average concentrations of respirable dust.
      METHODS: Data were studied from over 7000 men who had been surveyed in the late
      1970s. Linear regression equations for the association between FEV1 and self
      reported breathlessness on mild exertion were used to define clinically important
      levels of FEV1 deficit, and the probabilities that individuals with different
      dust exposures would experience these deficits were calculated. RESULTS: Levels
      of FEV1 were lower among breathless men than among others, with a large overlap
      of the distributions. The relations between standardised FEV1 and breathlessness
      were constant over all age and smoking groups. A decrease of 100 ml in FEV1 was
      associated with an increase of 1.12 in the odds of reporting breathlessness. FEV1
      deficits of -0.367, -0.627, and -0.993 l (designated as "small", "medium", and
      "large" deficits) were, on average, associated with proportional increases of
      risks of breathlessness by factors of 1.5, 2.0, and 3.0 respectively. Cumulative
      respirable dust exposure ranged up to 726 gh/m3, mean 136 gh/m3 (British Medical
      Research Council measurement convention). An increase of 50 gh/m3 was associated
      with an increase of about 2% in the proportion of men with small deficits in
      FEV1. For medium deficits the increases ranged from 1.5% to 2%, depending on age.
      A similar pattern was seen for large deficits, but with smaller increases.
      CONCLUSIONS: In the unlikely event of continuous exposure at the proposed new
      maximum respirable dust limit for British mines of 3 mg/m3 (ISO-CEN measurement
      convention) for a working lifetime, the risk of a medium deficit of FEV1 for a
      non-smoker at age 60 would be estimated to be 34%, compared with 25% for zero
      dust exposure; for smokers, about 54% compared with 44%.

PMID- 16621854
TI  - Effectiveness of a participative intervention on psychosocial work factors to
      prevent mental health problems in a hospital setting.
AB  - OBJECTIVES: To assess the effectiveness of a workplace intervention aimed at
      reducing adverse psychosocial work factors (psychological demands, decision
      latitude, social support, and effort-reward imbalance) and mental health problems
      among care providers. METHODS: A quasi-experimental design with a control group
      was used. Pre-intervention (71% response rate), and one-year post-intervention
      measures (69% response rate) were collected by telephone interviews. RESULTS: One
      year after the intervention, there was a reduction of several adverse
      psychosocial factors in the experimental group, whereas no such reduction was
      found in the control group. However, there was a significant deterioration of
      decision latitude and social support from supervisors in both experimental and
      control groups. There was also a significant reduction in sleeping problems and
      work related burnout in the experimental hospital, whereas only sleeping problems
      decreased in the control group while both client related and personal burnout
      increased in this hospital. The comparison between the experimental and control
      groups, after adjusting for pre-intervention measures, showed a significant
      difference in the means of all psychosocial factors except decision latitude. All
      other factors were better in the experimental group. CONCLUSION: Results suggest
      positive effects of the intervention, even though only 12 months have passed
      since the beginning of the intervention. Follow up at 36 months is necessary to
      evaluate whether observed effects are maintained over time. In light of these
      results, we believe that continuing the participative process in the experimental
      hospital will foster the achievement of a more important reduction of adverse
      psychosocial factors at work. It is expected that the intensity of the
      intervention will be directly related to its beneficial effects. Long term
      effects will however depend on the willingness of management and of staff to
      appropriate the process of identifying what contributes to adverse psychosocial
      factors at work and to adopt means to reduce them.

PMID- 16621853
TI  - Development and implementation of a participative intervention to improve the
      psychosocial work environment and mental health in an acute care hospital.
AB  - OBJECTIVES: To describe the development and implementation phases of a
      participative intervention aimed at reducing four theory grounded and empirically
      supported adverse psychosocial work factors (high psychological demands, low
      decision latitude, low social support, and low reward), and their mental health
      effects. METHODS: The intervention was realised among 500 care providers in an
      acute care hospital. A prior risk evaluation was performed, using a quantitative
      approach, to determine the prevalence of adverse psychosocial work factors and of
      psychological distress in the hospital compared to an appropriate reference
      population. In addition, a qualitative approach included observation in the care
      units, interviews with key informants, and collaborative work with an
      intervention team (IT) including all stakeholders. RESULTS: The prior risk
      evaluation showed a high prevalence of adverse psychosocial factors and
      psychological distress among care providers compared to a representative sample
      of workers from the general population. Psychosocial variables at work associated
      with psychological distress in the prior risk evaluation were high psychological
      demands (prevalence ratio (PR) = 2.27), low social support from supervisors and
      co-workers (PR = 1.35), low reward (PR = 2.92), and effort-reward imbalance (PR =
      2.65). These results showed the empirical relevance of an intervention on the
      four selected adverse psychosocial factors among care providers. Qualitative
      methods permitted the identification of 56 adverse conditions and of their
      solutions. Targets of intervention were related to team work and team spirit,
      staffing processes, work organisation, training, communication, and ergonomy.
      CONCLUSION: This study adds to the scarce literature describing the development
      and implementation of preventive intervention aimed at reducing psychosocial
      factors at work and their health effects. Even if adverse conditions in the
      psychosocial environment and solutions identified in this study may be specific
      to the healthcare sector, the intervention process used (participative problem
      solving) appears highly exportable to other work organisations.

PMID- 16621855
TI  - Shift work and work injury in the New Zealand Blood Donors' Health Study.
AB  - OBJECTIVE: To investigate associations between work patterns and the occurrence
      of work injury. METHODS: A cross sectional analysis of the New Zealand Blood
      Donors Health Study conducted among the 15 687 (70%) participants who reported
      being in paid employment. After measurement of height and weight, a self
      administered questionnaire collected information concerning occupation and work
      pattern, lifestyle behaviour, sleep, and the occurrence of an injury at work
      requiring treatment from a doctor during the past 12 months. RESULTS: Among paid
      employees providing information on work pattern, 3119 (21.2%) reported doing
      shift work (rotating with nights, rotating without nights, or permanent nights)
      and 1282 (8.7%) sustained a work injury. In unadjusted analysis, work injury was
      most strongly associated with employment in heavy manual occupations (3.6, 2.8 to
      4.6) (relative risk, 95% CI), being male (1.9, 1.7 to 2.2), being obese (1.7, 1.5
      to 2.0), working rotating shifts with nights (2.1, 1.7 to 2.5), and working more
      than three nights a week (1.9, 1.6 to 2.3). Snoring, apnoea or choking during
      sleep, sleep complaints, and excessive daytime sleepiness were also significantly
      associated with work injury. When mutually adjusting for all significant risk
      factors, rotating shift work, with or without nights, remained significantly
      associated with work injury (1.9, 1.5 to 2.4) and (1.8, 1.2 to 2.6),
      respectively. Working permanent night shifts was no longer significantly
      associated with work injury in the adjusted model. CONCLUSION: Work injury is
      highly associated with rotating shift work, even when accounting for increased
      exposure to high risk occupations, lifestyle factors, and excessive daytime
      sleepiness.

PMID- 16621856
TI  - Persisting risk of nickel related lung cancer and nasal cancer among Clydach
      refiners.
AB  - OBJECTIVE: To evaluate the risk of lung cancer and nasal cancer among workers
      employed at the Clydach nickel refinery, South Wales since 1930 by combining data
      from the two most recently published papers on this cohort. METHODS: Observed and
      expected numbers of cancer deaths were extracted for workers who had a minimum of
      five years service and were employed for the first time between 1902 and 1992.
      Standardised mortality ratios (SMR) were calculated for subgroups according to
      year of employment, time since first employment, and process work. RESULTS: A
      persisting excess of respiratory cancer was found for workers employed in the
      period 1930-92, with a lung cancer SMR of 133 (95% CI 103 to 172) and a SMR for
      nasal cancer of 870 (95% CI 105 to 3141). The lung cancer excess was most clearly
      seen 20 years or more after first employment and seemed to be confined to process
      workers. There was no indication of a further reduction in risk since 1930.
      CONCLUSION: The extreme nickel related cancer hazard at the refinery before 1920
      was greatly reduced during subsequent years. Some of the carcinogenic exposures
      seem to have remained after 1930, producing an elevated risk of nasal cancer and
      a 30% excess of lung cancer in the workforce. There was evidence of a persisting
      risk among process workers first employed since 1953.

PMID- 16621857
TI  - Public employees' health benefits survive major threats, so far.
AB  - Previous studies of public employees' health benefits indicate that they have
      been spared many of the changes evident in the private sector. But the recession
      and plunging state revenues in the early 2000s presented growing challenges to
      trying to preserve these benefits. Findings from the Round Five site visits of
      the Community Tracking Study (2005) reveal that benefits have still witnessed
      surprisingly few major modifications. But a growing gap between public- and
      private-sector benefits and new accounting requirements for government entities'
      retirement costs raise new threats to this protected status.

PMID- 16621858
TI  - The effect of zinc supplementation during pregnancy on immune response to Hib and
      BCG vaccines in Bangladesh.
AB  - An essential role for zinc in development of the fetal immune system has been
      documented. However, the effect of antenatal zinc supplementation on infants'
      postnatal immune response to vaccinations is unknown. The objective of this study
      was to evaluate the effect of zinc supplementation during pregnancy on immune
      response to the Bacillus Calmette-Guerin (BCG) vaccine and the Haemophilus
      influenzae type b (Hib) component of the combined diphtheria, tetanus toxoid and
      pertussis (DTP)-Haemophilus influenzae type-b (Hib)- conjugate vaccine in poor
      Bangladeshi infants. We immunized 405 infants whose mothers were supplemented
      daily with 30 mg elemental zinc or placebo beginning at 12-16 weeks gestation
      with the standard BCG vaccine at birth. A subcohort of 203 infants were in
      addition immunized at 1-month intervals with three doses of DTP-Hib vaccine
      starting at 9 weeks of age. The delayed hypersensitivity (PPD) skin test was
      performed in 345 infants at 24 weeks of age. Hib polysaccharide (PRP) antibodies
      were assessed for 91 infants at 4 and 24 weeks of age. In infants born with low
      birth weight (LBW) a lower proportion of negative responses to PPD skin test were
      observed in the zinc (66.2%) compared to placebo (78.5%) group (p = 0.07). No
      differences were observed in normal birth weight infants. There were no
      differences in proportion of infants above the protective thresholds for anti-PRP
      antibodies between zinc (81%) and placebo (89%) group. Geometric mean PRP
      antibody titres at 4 and 24 weeks of age were not different between groups. Zinc
      supplementation during pregnancy did not enhance immune response to Hib-conjugate
      vaccine but there was a suggestion of improved delayed hypersensitivity immune
      responses to BCG-vaccine in Bangladeshi LBW infants.

PMID- 16621859
TI  - Isolation of individual egg cells and zygotes in Alstroemeria followed by manual
      selection with a microcapillary-connected micropump.
AB  - AIMS: To develop a procedure for isolating living egg cells and zygotes from
      Alstroemeria ovules. SCOPE: An attempt was made to isolate egg cells and zygotes
      from the ovules of Alstroemeria aurea. The ovules were histologically observed
      using a clearing procedure which revealed the localization and sizes of the
      embryo sacs and egg apparatus within the ovules. For the isolation of egg cells,
      ovules were cut into sections with a surgical blade and treated with an enzyme
      solution. Subsequently, these ovule sections were dissected using a glass needle
      under an inverted microscope. Egg cells successfully isolated by this procedure
      were collected using microcapillaries connected to a micropump. For zygote
      isolation, ovules were excised from ovaries 24 h after self-pollination. By
      treating excised ovules with an enzyme solution and subsequently dissecting them
      using a glass needle, zygotes were successfully isolated from the ovules and
      collected with a microcapillary. The isolated zygotes were associated with pollen
      tubes and one of the synergids. Egg cells and zygotes were viable for up to 2 h
      following isolation, as determined by fluorescein diacetate staining.
      CONCLUSIONS: The procedures for isolating egg cells and zygotes in Alstroemeria
      were established, and each egg cell and zygote was captured with a
      microcapillary.

PMID- 16621860
TI  - Drought tolerance of selected Eragrostis species correlates with leaf tensile
      properties.
AB  - BACKGROUND AND AIMS: Previous studies on grass leaf tensile properties (behaviour
      during mechanical stress) have focused on agricultural applications such as
      resistance to trampling and palatability; no investigations have directly
      addressed mechanical properties during water stress, and hence these are the
      subject of this study. METHODS: Critical (lethal) relative water contents were
      determined for three species of grass in the genus Eragrostis varying in their
      tolerance to drought. Measurements were taken for leaf tensile strength, elastic
      modulus, toughness and failure load under different conditions of hydration, and
      light microscopy and histochemical analyses were undertaken. KEY RESULTS: Leaf
      tensile strength of fully hydrated leaves for the drought-intolerant E. capensis,
      the moderately drought-tolerant E. tef and the drought-tolerant E. curvula
      correlated well with drought tolerance (critical relative water content).
      Eragrostis curvula had higher tensile strength values than E. tef, which in turn
      had higher values than E. capensis. Measurements on the drought-tolerant grass E.
      curvula when fully hydrated and when dried to below its turgor loss point showed
      that tensile strength, toughness and the elastic modulus all increased under
      conditions of turgor loss, while the failure load remained unchanged. Additional
      tests of 100 mm segments along the lamina of E. curvula showed that tensile
      strength, toughness and the elastic modulus all decreased with distance from the
      base of the lamina, while again the failure load was unaffected. This decrease in
      mechanical parameters correlated with a reduction in the size of the vascular
      bundles and the amount of lignification, as viewed in lamina cross-sections.
      CONCLUSIONS: The results confirm that leaf mechanical properties are affected by
      both water status and position along the lamina, and suggest a positive
      correlation between leaf internal architecture, tensile strength, cell wall
      chemistry and tolerance to dehydration for grasses.

PMID- 16621861
TI  - Inter- and intraspecific variation in the germination response to light quality
      and scarification in grasses growing in two-phase mosaics of the Chihuahuan
      Desert.
AB  - BACKGROUND AND AIMS: In many locations, plants are faced with adjacent,
      contrasting environments, and the between-species differential evolution of life
      history traits can be interpreted as an evolutionary response to this
      environmental heterogeneity. However, there has been little research on the
      intraspecific variability in these attributes as a possible evolutionary response
      of plants. METHODS: In the two-phase mosaic of the Chihuahuan Desert (adjacent
      patches with contrasting resource availability), analyses were carried out of the
      germination response to the scarification and light quality to which grass seeds
      growing on these patches are exposed (open and closed habitats). KEY RESULTS:
      Species that grow in open habitats exhibited a higher germination success than
      those from closed habitats after scarification. At both the inter- and
      intraspecific level, there were differences in the germination percentage and in
      the germination speed in response to light quality. Intraspecific variation in
      the species from the closed habitat (Pleuraphis mutica and Trichloris crinita)
      and in Chloris virgata (which grows in both habitats) was due to genetic
      variation (the family factor was significant), but there was no genetic variation
      in phenotypic plasticity (non-significant interaction between family and light
      quality). In contrast, for the species that grows only in the open habitat
      (Dasyochloa pulchella), the family did not have a significant effect, but there
      was genetic variation in the phenotypic plasticity (significant interaction
      between family and light quality). CONCLUSIONS: In C. virgata, P. mutica and T.
      crinita, natural selection could be favouring those genotypes that responded
      better in each light environment, but it is not possible that the natural
      selection resulted in different optimal phenotypes in each habitat. On the
      contrary, in D. pulchella, selection could have reduced the genetic variation,
      but there is the possibility of the evolution of reaction norms, resulting in the
      selection of alternative phenotypes for each habitat.

PMID- 16621863
TI  - Temporal artery biopsy in ophthalmology: a useful investigation.

PMID- 16621864
TI  - Weasel words.

PMID- 16621865
TI  - CD45 regulates apoptosis in peripheral T lymphocytes.
AB  - Programmed cell death (apoptosis) is a key mechanism for regulating lymphocyte
      numbers. Murine lymph node lymphocytes cultured in vitro without added stimuli
      show significant levels of apoptosis over 24 h, detectable by staining with
      Annexin V. CD4 and CD8 T lymphocytes from transgenic (Tg) mice expressing single
      CD45RABC or CD45RO isoforms show increased apoptosis and the extent of apoptosis
      is inversely correlated with the level of CD45 expression. CD45 Tg cells exhibit
      phosphatidyl serine translocation and DNA oligonucleosome formation, and can be
      partially rescued from apoptosis by culture in caspase inhibitors or common gamma
      chain-binding cytokines. We conclude that CD45 is an important regulator of
      spontaneous apoptosis in T lymphocytes and this mechanism may contribute to the
      disease associations reported for individuals expressing CD45 variant alleles.

PMID- 16621866
TI  - Recruitment and proliferation of CD4+ T cells in synovium following adoptive
      transfer of adjuvant-induced arthritis.
AB  - Adjuvant-induced arthritis can be transferred to naive Dark Agouti (DA) strain
      (DA.CD45.1) rats by thoracic duct (TD) lymphocytes. Disease can be re-induced in
      convalescent rats by further transfer of arthritogenic cells, suggesting that
      resolution of the adoptive disease is not due to active regulation. To examine
      whether resolution is due to exhaustion of effector cells, we transferred the
      disease to DA.CD45.1 recipients, using CD4+ T cells from DA.CD45.2 donors. At the
      height of the adoptively transferred disease, donor cells comprised only 5-10% of
      recirculating CD4+ T cells but they accounted for approximately 40% of the CD4+ T
      cells in synovium-rich tissues of the hind paws. Approximately 65% of the donor
      cells in the synovium expressed a marker of proliferation (Ki-67 antigen).
      Division of CD4+ T cells continued in shielded paws after suppression of the
      recirculating pool of lymphocytes by selective irradiation. Intravenously
      injected CD4+ TD T lymphoblasts from arthritic donors were recruited to normal
      paws and, in greater numbers, to paws of animals with existing arthritis.
      Survival of the [125I]iodo-deoxyuridine-labeled lymphoblasts was greater in
      animals with existing arthritis. We conclude that effector CD4+ T cells in target
      tissues can proliferate in response to autoantigens and exhibit enhanced
      survival. However, without a continuous supply, adoptively transferred effector
      cells do not produce autonomous local disease, due to limits to their lifespan
      and ability to replicate indefinitely.

PMID- 16621867
TI  - CD4+ T cell-independent maintenance and expansion of memory CD8+ T cells derived
      from in vitro dendritic cell activation.
AB  - CD4+ T cells are essential for the maintenance of CD8+ memory T (Tm) cells
      following acute infection, but the importance of CD4+ T cells for the maintenance
      and expansion of CD8+ Tm cells to non-infectious antigens remains mostly unknown.
      Here, we showed that ovalbumin (OVA)-specific CD8+ Tm cell precursors derived
      from in vitro stimulation of TCR transgenic OT I CD8+ T cells with OVA protein
      pulsed bone marrow-derived dendritic cells (DCOVA) can give rise to functional
      CD8+ Tm cells after adoptively transferred into mice. These CD8+ Tm cells can be
      maintained and remain fully functional in CD4+ T cell-absent environments in
      vivo. Furthermore, CD4+ T cells are not essential for the expansion of these CD8+
      Tm cells. Finally, these in vitro DCOVA-activated CD8+ Tm cells maintained in CD4
      deficient mice are also able to confer fully protective immunity against a later
      challenge of OVA-expressing tumor cells. Collectively, these findings demonstrate
      that in contrast to acute infections, maintenance and expansion of CD8+ Tm cells
      after priming with OVA protein-pulsed dendritic cells are independent of CD4+ T
      cells.

PMID- 16621868
TI  - Differential effects of short-term lipid lowering with ezetimibe and statins on
      endothelial function in patients with CAD: clinical evidence for 'pleiotropic'
      functions of statin therapy.
AB  - AIMS: Statin therapy is associated with improved endothelial vasodilator
      function. The clinical availability of ezetimibe, a potent novel cholesterol
      absorption inhibitor, enables to differentiate lipid-lowering effects from
      potential non-lipid-lowering (pleiotropic) mechanisms of statins. METHODS AND
      RESULTS: Forearm blood flow (FBF) responses to acetylcholine (ACH) and sodium
      nitroprusside (SNP) were measured by venous occlusion plethysmography in four
      prospectively defined groups of patients with stable coronary artery disease
      (CAD) before and after 4 weeks of lipid-lowering therapy. Group A (n=15): de novo
      monotherapy with 10 mg/day ezetimibe; Group B (n=15): 10 mg/day ezetimibe as an
      add-on to chronic simvastatin therapy with 20 mg/day; Group C (n=15): dose
      escalation from chronic 10 to 40 mg/day atorvastatin; and Group D (n=15): de novo
      monotherapy with 40 mg/day atorvastatin. After 4 weeks of therapy, LDL
      cholesterol levels were significantly reduced in all four groups. Neither
      ezetimibe monotherapy (Group A) nor ezetimibe combined with 20 mg simvastatin
      (Group B) was associated with an increase in ACH-mediated FBF responses after 4
      weeks. In contrast, dose escalation of atorvastatin from 10 to 40 mg/day (Group
      C) or de novo therapy with 40 mg atorvastatin/day (Group D) was associated with a
      significant increase in ACH-mediated FBF responses (P<0.013). CONCLUSION: Thus,
      both statins and ezetimibe effectively lower LDL-levels within 4 weeks of
      therapy. However, only statin therapy is associated with improved endothelial
      vasodilator function, disclosing the relevance of pleiotropic effects of statins
      during short-term treatment of patients with CAD.

PMID- 16621869
TI  - Plasma N-terminal fragments of natriuretic propeptides predict the risk of
      cardiovascular events and mortality in middle-aged men.
AB  - AIMS: The prognostic significance of N-terminal pro-A-type (NT-proANP) and pro-B
      type natriuretic peptides (NT-proBNP) is not well documented in population-based
      prospective studies. We, therefore, studied if both NT-proANP and NT-proBNP are
      predictive for overall death, cardiovascular events, and atrial fibrillation (AF)
      among middle-aged men without heart failure or AF at baseline. METHODS AND
      RESULTS: Plasma NT-proANP and NT-proBNP were measured in a representative
      population-based sample of 905 men (age 46-65 years) from eastern Finland. There
      were 110 deaths [58 cardiovascular and 40 coronary heart disease (CHD)] and 59
      cases of AF during a follow-up of 10 years. The multivariable adjusted risk for
      overall was 1.35-fold (95% CI 1.15-1.57) and 1.52-fold (95% CI 1.21-1.91) for CHD
      death for each SD (160.8 pmol/L) increment in NT-proANP. The respective risks
      were 1.26-fold (95% CI 1.12-1.42) and 1.44-fold (95% CI 1.22-1.60) for each SD
      (58.9 pmol/L) increment in NT-proBNP. The adjusted risks for future AF were 1.46
      (P<0.001) and 1.72-fold (P<0.001) for each SD increment in NT-proANP and NT
      proBNP, respectively. CONCLUSION: The main finding of the present study is that
      NT-proANP and NT-proBNP are strong predictors of death from cardiovascular and
      other causes including AF. These natriuretic peptides add to the prognostic value
      of conventional risk factors and provide a non-invasive measure for identifying
      men with high risk of death and its co-morbidities.

PMID- 16621870
TI  - Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of
      non-responders compared with clopidogrel in aspirin-treated patients with stable
      coronary artery disease.
AB  - AIMS: This study was designed to compare the degree of inhibition of platelet
      aggregation (IPA) of prasugrel with that of clopidogrel in stable aspirin-treated
      patients with coronary artery disease (CAD). METHODS AND RESULTS: Subjects
      (n=101) were randomly assigned to the following loading dose (LD) (day
      1)/maintenance dose (MD) (days 2-28) combinations: prasugrel, 40 mg/5 mg; 40
      mg/7.5 mg; 60 mg/10 mg; 60 mg/15 mg; or clopidogrel, 300 mg/75 mg. Turbidometric
      platelet aggregation was measured at multiple timepoints during the study. At 4 h
      after dosing, with 20 microM ADP, both prasugrel LDs achieved significantly
      higher mean IPA levels (60.6% and 68.4 vs. 30.0%, respectively; all P<0.0001) and
      lower percentage (3 vs. 52%, P<0.0001) of pharmacodynamic non-responders (defined
      as IPA <20%) than clopidogrel. Prasugrel 10 and 15 mg MDs achieved consistently
      higher mean IPA than clopidogrel 75 mg at day 28 (all P<0.0001). At pre-MD on day
      28, there were no non-responders in the 10 and 15 mg prasugrel group, compared
      with 45% in the clopidogrel group (P=0.0007). CONCLUSION: In this population,
      prasugrel (40-60 mg LD and 10-15 mg MD) achieves greater IPA and a lower
      proportion of pharmacodynamic non-responders compared with the approved
      clopidogrel dosing.

PMID- 16621871
TI  - Non-fluoroscopic mapping systems for electrophysiology: the 'tool or toy' dilemma
      after 10 years.

PMID- 16621872
TI  - The pathology of myocardial infarction in the pre- and post-interventional era.

PMID- 16621873
TI  - Tissue Doppler velocity is superior to displacement and strain mapping in
      predicting left ventricular reverse remodelling response after cardiac
      resynchronisation therapy.
AB  - OBJECTIVE: To compare the values of three different forms of tissue Doppler
      imaging (TDI) processing in predicting left ventricular (LV) reverse remodelling
      namely, tissue velocity, displacement and strain mapping. DESIGN: Standard
      echocardiography with TDI was performed before and 3 months after cardiac
      resynchronisation therapy (CRT). SETTING: University teaching hospital. PATIENTS:
      55 patients with heart failure who received CRT and were followed up for at least
      3 months were recruited. INTERVENTIONS: During off-line analysis, the time to
      peak systolic velocity in the ejection phase, time to peak positive displacement
      and time to peak negative strain were measured in the six basal, six mid
      segmental model. Parameters of systolic asynchrony derived by velocity,
      displacement and strain mapping were correlated with percentage reduction in LV
      end systolic volume (LVESV) and absolute gain in ejection fraction (EF). RESULTS:
      Among the three TDI processing technologies, all parameters of tissue velocity
      correlated with LV reverse remodelling (r = -0.49 to r = -0.76, all p < 0.001),
      but the predictive value was strongest in models with 12 LV segments. For
      displacement mapping, only the two parameters that included 12 LV segments
      correlated modestly with reduction in LVESV (r = -0.36, p < 0.05) and gain in EF.
      However, none of the strain mapping parameters predicted a favourable
      echocardiographic response. The receiver operating characteristic (ROC) curve
      areas were higher for parameters of tissue velocity based on 12 LV segments (ROC
      areas 0.88 and 0.94) than the corresponding areas derived from displacement
      mapping (ROC areas 0.72 and 0.71). CONCLUSION: Tissue velocity parameters of
      systolic asynchrony are superior to those of displacement and strain mapping in
      predicting LV reverse remodelling response after CRT.

PMID- 16621874
TI  - Circulating adiponectin concentrations in patients with congestive heart failure.
AB  - OBJECTIVES: To determine concentrations of adiponectin and its predictive value
      on outcome in a cohort of patients with congestive heart failure (CHF). METHODS:
      Serum and clinical data were obtained for outpatients with clinically controlled
      CHF (n = 175). Serum concentrations of adiponectin, C reactive protein, N
      terminal pro-brain natriuretic peptide (NT-proBNP), interleukin (IL) -1beta, IL
      6, IL-8, IL-10, IL-12, tumour necrosis factor alpha and CD-40 ligand were
      determined. The association of adiponectin with the clinical severity of CHF was
      sought as well as the predictive value of this adipokine on mortality, CHF
      hospitalisations or the occurrence of each of these end points. RESULTS:
      Concentrations of adiponectin were significantly increased in patients with CHF.
      Patients with higher New York Heart Association class had significantly higher
      serum concentrations of adiponectin. Adiponectin serum concentrations were lower
      in patients with diabetes and CHF as well as in patients with ischaemic
      cardiomyopathy. Serum adiponectin concentration was positively associated with
      age and NT-proBNP but was negatively correlated with C reactive protein
      concentrations. Serum adiponectin above the 75th centile was found to be an
      independent predictor of total mortality, CHF hospitalisations or a composite of
      these end points over a two-year prospective follow up. CONCLUSION: Adiponectin
      is increased in CHF patients and predicts mortality and morbidity.

PMID- 16621875
TI  - Excessive breathlessness in patients with diastolic heart failure.
AB  - OBJECTIVES: To establish the prevalence of preserved left ventricular (LV)
      systolic function (PSF) in 435 consecutive symptomatic patients referred to a
      heart failure clinic and to examine their ventilatory response to exercise when
      compared with 134 control volunteers. METHODS: 216 (50%) patients had systolic
      heart failure (SHF) (ejection fraction < 45%). 51 (11%) had an immediately
      apparent alternative causes of breathlessness and 168 (39%), with no obvious
      other cause of breathlessness, were divided into those with PSF and diastolic
      dysfunction (DD) (PSF(DD); n = 113 or 26% of referrals) and those without DD
      (PSF(N); n = 55 or 13% of referrals). The controls were divided into those with
      (C(DD); n = 32) and those without (C(N); n = 102) echocardiographic evidence of
      DD. RESULTS: Patients with SHF had lower peak oxygen consumption (pVo(2)),
      steeper slope of minute ventilation (Ve) to carbon dioxide production, lower
      exercise time and shorter 6 min walk test than PSF patients and controls. PSF(DD)
      patients had lower pVo(2), exercise time and 6 min walk test than C(DD), although
      their echocardiograms were not different. Exercise capacity did not differ
      between PSF(DD) and PSF(N) patients. The slope relating Ve to symptoms (Borg/Ve
      slope) was less steep in those with SHF than in PSF(DD) (0.17 (0.04) v 0.20
      (0.08), p < 0.05) and in PSF(N) (0.19 (0.10), p < 0.05), implying greater
      symptoms of breathlessness for a given level of Ve. Both PSF groups had a steeper
      slope than C(DD) (0.14 (0.09), p < 0.05 for both comparisons). CONCLUSIONS:
      Patients with PSF have exercise tolerance intermediate between that of patients
      with SHF and controls. Exercise tolerance is similar in PSF(DD) and PSF(N). Both
      groups have worse exercise tolerance than C(DD). PSF(DD) and PSF(N) patients seem
      to experience a greater awareness of Ve than C(DD) and patients with SHF.

PMID- 16621876
TI  - Glucose and haemoglobin in the assessment of prognosis after first
      hospitalisation for heart failure.
AB  - OBJECTIVE: To examine the relationship with outcome of plasma haemoglobin and
      glucose concentrations, measured soon after first hospital admission with chronic
      heart failure (CHF), in standard clinical practice. METHODS AND RESULTS: Hospital
      records of 528 patients (43% women, mean age 70 years) with first hospital
      admission for CHF were reviewed. During follow up (mean 1257 days, range 520
      1800), 240 (45%) patients died. On admission, 140 of 528 (27%) and at discharge
      179 of 472 survivors (38%) were receiving treatment for diabetes. World Health
      Organization criteria for anaemia were met by 39% of men and 43% of women. Lower
      haemoglobin (hazard ratio 0.879, 95% confidence interval (CI) 0.828 to 0.933, p <
      0.0001) and higher plasma glucose (hazard ratio 1.034, 95% CI 1.008 to 1.061, p =
      0.009) had univariate association with all-cause mortality. On multivariate
      analysis, compared with patients with a normal haemoglobin for their sex, hazard
      ratio was 1.415 (95% CI 1.087 to 1.841, p = 0.010) for those with low
      haemoglobin. All-cause mortality fell linearly for haemoglobin up to 159 g/l,
      above which mortality increased. Glucose above the highest quartile (> 10 mmol/l)
      was an independent predictor of mortality (hazard ratio 1.966, 95% CI 1.376 to
      2.810, p = 0.0002). In survivors of the index admission the association between
      glucose and mortality was linear, the relationship being stronger for patients
      without diabetes. CONCLUSIONS: Lower haemoglobin and higher plasma glucose are
      associated with all-cause mortality in CHF. Higher glucose is associated with
      mortality irrespective of diabetic status.

PMID- 16621877
TI  - A history of arterial hypertension does not affect mortality in patients
      hospitalised with congestive heart failure.
AB  - OBJECTIVES: To evaluate the importance of a history of hypertension on long-term
      mortality in a large cohort of patients hospitalised with congestive heart
      failure (CHF). DESIGN: Retrospective analysis of 5491 consecutive patients, of
      whom 24% had a history of hypertension. 60% of the patients had non-systolic CHF,
      and 57% had ischaemic heart disease. SETTING: 38 primary, secondary and tertiary
      hospitals in Denmark. MAIN OUTCOME MEASURES: Total mortality 5-8 years after
      inclusion in the registry. RESULTS: Female sex and preserved left ventricular
      systolic function was more common among patients with a history of hypertension.
      72% of the patients died during follow up. A hypertension history did not affect
      mortality risk (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.92 to
      1.07). Correction for differences between the normotensive and hypertensive
      groups at baseline in a multivariate model did not alter this result (HR 1.08,
      95% CI 1.00 to 1.17, p = 0.06). The hazard ratio was similar in patients with and
      without a history of ischaemic heart disease. Hence, a specific effect of
      hypertension in the group of patients with CHF with ischaemic heart disease, as
      suggested in earlier studies, could not be confirmed. CONCLUSION: A history of
      arterial hypertension did not affect mortality in patients hospitalised with CHF.

PMID- 16621878
TI  - Splenectomy: a strong risk factor for pulmonary hypertension in patients with
      thalassaemia.
AB  - OBJECTIVE: To determine the association between splenectomy and pulmonary
      hypertension in patients with thalassaemia with anaemia. DESIGN: Prospective
      cross-sectional study. METHODS: 68 patients with thalassaemia, who had a
      haemoglobin concentration of less than 100 g/l, were recruited into this study.
      Echocardiography was performed before clinical data were reviewed. Pulmonary
      artery pressure was estimated by measuring the systolic transtricuspid pressure
      gradient from tricuspid regurgitation and adding it to the right atrial pressure,
      which was estimated by the response of the inferior vena cava to inspiration.
      Pulmonary hypertension was defined as systolic pulmonary artery pressure > 35 mm
      Hg. History of splenectomy and other clinical data were compared between patients
      with and without pulmonary hypertension. RESULTS: 29 patients had pulmonary
      hypertension and 39 did not. Patients with pulmonary hypertension had
      significantly more nucleated red blood cells and higher platelet counts, and a
      higher prevalence of splenectomy (75.8% v 25.6%, odds ratio 9.1, 95% confidence
      interval 3.0 to 27.7). In multivariate analysis, splenectomy was the only factor
      significantly related to pulmonary hypertension. CONCLUSION: Splenectomy is a
      strong risk factor for pulmonary hypertension in patients with thalassaemia.

PMID- 16621880
TI  - Risk scoring for percutaneous coronary intervention: let's do it!

PMID- 16621879
TI  - Effects of torasemide on cardiac sympathetic nerve activity and left ventricular
      remodelling in patients with congestive heart failure.
AB  - OBJECTIVE: To determine the effect of torasemide, a loop diuretic with
      antialdosteronergic properties, compared with furosemide on cardiac sympathetic
      nerve activity in patients with congestive heart failure (CHF). METHODS: 40
      patients with non-ischaemic CHF (left ventricular ejection fraction (LVEF) < 45%)
      were randomly assigned to torasemide (4-8 mg/day; n = 20) or furosemide (20-40
      mg/day; n = 20). All patients were also treated with angiotensin-converting
      enzyme inhibitor. The delayed heart to mediastinum count (H/M) ratio, delayed
      total defect score (TDS) and washout rate were determined from iodine-123 meta
      iodobenzylguanidine measured before and 6 months after treatment. Left
      ventricular end diastolic volume (LVEDV), left ventricular end systolic volume
      (LVESV) and LVEF were also determined by echocardiography. RESULTS: After
      treatment, in patients receiving torasemide, TDS decreased from 44 (8) to 36 (8)
      (p < 0.001), H/M ratio increased from 1.61 (0.19) to 1.77 (0.24) (p < 0.001), and
      washout rate decreased from 52 (12)% to 41 (14)% (p = 0.001). In addition, LVEDV
      decreased from 173 (22) ml to 147 (30) ml (p < 0.001) and LVESV decreased from
      117 (19) ml to 95(24) ml (p < 0.001). Although LVEF tended to increase, the
      change was not significant (from 31 (7)% to 34 (7)%, NS). Conversely, these
      parameters did not change significantly in patients receiving furosemide.
      Moreover, percentage change of TDS was significantly correlated with percentage
      change of LVEDV (r = 0.473, p < 0.05) and of LVESV (r = 0.579, p < 0.01) after
      torasemide treatment. CONCLUSION: These findings indicate that torasemide
      treatment can ameliorate cardiac sympathetic nerve activity and left ventricular
      remodelling in patients with CHF.

PMID- 16621881
TI  - Low-gradient aortic valve stenosis: value and limitations of dobutamine stress
      testing.
AB  - Aortic valve stenosis has already reached endemic proportions in Western
      countries. As the prognosis of low-flow aortic valve stenosis under medical
      treatment is dismal, surgery is recommended in most patients. Preoperative
      dobutamine stress testing may help to assess surgical risk, but there is no
      strong scientific evidence to deny surgery based exclusively on the results of
      this test. The problems associated with clinical decision making in this
      condition are reviewed.

PMID- 16621882
TI  - Interventional versus conservative treatment in acute non-ST elevation coronary
      syndrome: time course of patient management and disease events over one year in
      the RITA 3 trial.
AB  - OBJECTIVE: To determine whether, in acute non-ST elevation coronary syndrome, the
      benefit from early invasive coronary intervention compared with a conservative
      strategy of later symptom-guided intervention varies over time. METHODS: In RITA
      3 (Randomised Intervention Trial of unstable Angina 3) patients were randomly
      assigned to coronary angiography (median 2 days after randomisation) and
      appropriate intervention (n = 895) or to a symptom-guided conservative strategy
      (n = 915). RESULTS: In the first week patients in both groups were at highest
      risk of death, myocardial infarction (MI) or refractory angina (incidence rate 40
      times higher than in months 5-12 of follow up). There were 22 MIs and 6 deaths in
      the intervention group (largely due to procedure-related events, 14 MIs and 3
      deaths) versus 17 MIs and 3 deaths in the conservative group. In the rest of the
      year there were an additional 12 versus 27 MIs, respectively (treatment-time
      interaction p = 0.021). Over one year in the intervention group there was a 43%
      reduction in refractory angina; 22% of patients underwent coronary artery bypass
      surgery and 35% underwent percutaneous coronary intervention only, which reduced
      refractory angina but provoked some early MIs; and 43% were still treated
      medically, mostly because of a favourable initial angiogram. CONCLUSION: Any
      intervention policy needs to recognise the high risk of events in the first week
      and the substantial minority of patients not needing intervention. Intervention
      may be best targeted at higher risk patients, as the early hazards of the
      procedure are then offset by reduced subsequent events.

PMID- 16621883
TI  - Accuracy and impact of risk assessment in the primary prevention of
      cardiovascular disease: a systematic review.
AB  - OBJECTIVE: To determine the accuracy of assessing cardiovascular disease (CVD)
      risk in the primary prevention of CVD and its impact on clinical outcomes.
      DESIGN: Systematic review. DATA SOURCES: Published studies retrieved from Medline
      and other databases. Reference lists of identified articles were inspected for
      further relevant articles. SELECTION OF STUDIES: Any study that compared the
      predicted risk of coronary heart disease (CHD) or CVD, with observed 10-year risk
      based on the widely recommended Framingham methods (review A). Randomised
      controlled trials examining the effect on clinical outcomes of a healthcare
      professional assigning a cardiovascular risk score to people predominantly
      without CVD (review B). REVIEW METHODS: Data were extracted on the ratio of the
      predicted to the observed 10-year risk of CVD and CHD (review A), and on
      cardiovascular or coronary fatal or non-fatal events, risk factor levels,
      absolute cardiovascular or coronary risk, prescription of risk-reducing drugs and
      changes in health-related behaviour (review B). RESULTS: 27 studies with data
      from 71,727 participants on predicted and observed risk for either CHD or CVD
      were identified. For CHD, the predicted to observed ratios ranged from an
      underprediction of 0.43 (95% CI 0.27 to 0.67) in a high-risk population to an
      overprediction of 2.87 (95% CI 1.91 to 4.31) in a lower-risk population. In
      review B, four randomised controlled trials confined to people with hypertension
      or diabetes found no strong evidence that a cardiovascular risk assessment
      performed by a clinician improves health outcomes. CONCLUSION: The performance of
      the Framingham risk scores varies considerably between populations and evidence
      supporting the use of cardiovascular risk scores for primary prevention is
      scarce.

PMID- 16621884
TI  - Assessment of the relationship between cerebral and splanchnic oxygen saturations
      measured by near-infrared spectroscopy and direct measurements of systemic
      haemodynamic variables and oxygen transport after the Norwood procedure.
AB  - OBJECTIVES: To evaluate the clinical utility of near-infrared spectroscopic
      (NIRS) monitoring of cerebral (ScO2) and splanchnic (SsO2) oxygen saturations for
      estimation of systemic oxygen transport after the Norwood procedure. METHODS:
      ScO2 and SsO2 were measured with NIRS cerebral and thoracolumbar probes (in
      humans). Respiratory mass spectrometry was used to measure systemic oxygen
      consumption (O2). Arterial (SaO2), superior vena caval (SvO2) and pulmonary
      venous oxygen saturations were measured at 2 to 4 h intervals to derive pulmonary
      (Qp) and systemic blood flow (Qs), systemic oxygen delivery (DO2) and oxygen
      extraction ratio (ERO2). Mixed linear regression was used to test correlations. A
      study of 7 pigs after cardiopulmonary bypass (study 1) was followed by a study of
      11 children after the Norwood procedure (study 2). RESULTS: Study 1. ScO2
      moderately correlated with SvO2, mean arterial pressure, Qs, DO2 and ERO2 (slope
      0.30, 0.64. 2.30, 0.017 and -32.5, p < 0.0001) but not with SaO2, arterial oxygen
      pressure (PaO2), haemoglobin and O2. Study 2. ScO2 correlated well with SvO2,
      SaO2, PaO2 and mean arterial pressure (slope 0.43, 0.61, 0.99 and 0.52, p <
      0.0001) but not with haemoglobin (slope 0.24, p > 0.05). ScO2 correlated weakly
      with O2 (slope -0.07, p = 0.05) and moderately with Qs, DO2 and ERO2 (slope 3.2,
      0.03, -33.2, p < 0.0001). SsO2 showed similar but weaker correlations.
      CONCLUSIONS: ScO2 and SsO2 may reflect the influence of haemodynamic variables
      and oxygen transport after the Norwood procedure. However, the interpretation of
      NIRS data, in terms of both absolute values and trends, is difficult to rely on
      clinically.

PMID- 16621885
TI  - Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor
      alpha.
AB  - Natural products derived from plants provide a rich source for development of new
      anticancer drugs. Recent studies suggest that modulation of subcellular
      localization of retinoid X receptor-alpha (RXRalpha) represents a potential
      approach for inducing cancer cell apoptosis. In this study, we screened a herbal
      library for inducing translocation of RXRalpha from the nucleus to the cytoplasm.
      Our results revealed that the extract of Hypericum sampsonii, a member of the
      genus Hypericum, had remarkable effect on RXRalpha subcellular localization in
      various cancer cells. Treatment of NIH-H460 human lung cancer cells with H.
      sampsonii extract resulted in relocalization of RXRalpha from the nucleus to the
      cytoplasm. Cytoplasmic RXRalpha induced by H. sampsonii was associated with
      mitochondria, accompanied with cytochrome c release and apoptosis. H. sampsonii
      extract effectively inhibited the growth of various cancer cell lines, including
      NIH-H460 lung cancer, MGC-803 stomach cancer and SMMC7721 liver cancer cells. The
      growth inhibitory effect of H. sampsonii extract depended on levels of RXRalpha,
      as it failed to inhibit the growth of CV-1 cells lacking detectable RXRalpha,
      whereas transfection of RXRalpha into CV-1 cells restored its apoptotic response
      to H. sampsonii. Furthermore, the apoptotic effect of H. sampsonii was
      significantly enhanced when RXRalpha was overexpressed in NIH-H460 cells.
      Together, our results demonstrate that H. sampsonii contains ingredient(s) that
      induce apoptosis of cancer cells by modulating subcellular localization of
      RXRalpha.

PMID- 16621886
TI  - Berberine inhibits growth, induces G1 arrest and apoptosis in human epidermoid
      carcinoma A431 cells by regulating Cdki-Cdk-cyclin cascade, disruption of
      mitochondrial membrane potential and cleavage of caspase 3 and PARP.
AB  - Chemotherapeutic approach using non-toxic botanicals may be one of the strategies
      for the management of the skin cancers. Here we report that in vitro treatment of
      human epidermoid carcinoma A431 cells with berberine, a naturally occurring
      isoquinoline alkaloid, decreased cell viability (3-77%, P < 0.05-0.001) and
      induced cell death (3-51%, P < 0.01-0.001) in a dose (5-75 microM)- and time (12
      72 h)-dependent manner, which was associated with an increase in G(1) arrest.
      G(0)/G(1) phase of the cell cycle is known to be controlled by cyclin dependent
      kinases (Cdk), cyclin kinase inhibitors (Cdki) and cyclins. Our western blot
      analysis showed that berberine-induced G(1) cell cycle arrest was mediated
      through the increased expression of Cdki proteins (Cip1/p21 and Kip1/p27), a
      simultaneous decrease in Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and enhanced
      binding of Cdki-Cdk. In additional studies, treatment of A431 cells with
      berberine (15-75 microM) for 72 h resulted in a significant dose-dependent
      increase in apoptosis (31-60%, P < 0.05-0.001) than non-berberine-treated control
      (11.7%), which was associated with an increased expression of pro-apoptotic
      protein Bax, decreased expression of anti-apoptotic proteins Bcl-2 and Bcl-xl,
      disruption of mitochondrial membrane potential, and activation of caspases 9, 3
      and poly (ADP-ribose) polymerase. Pretreatment of A431 cells with the pan-caspase
      inhibitor (z-VAD-fmk) significantly blocked the berberine-induced apoptosis in
      A431 cells confirmed that berberine-induced apoptosis is mediated through
      activation of caspase 3-dependent pathway. Together, this study for the first
      time identified berberine as a chemotherapeutic agent against human epidermoid
      carcinoma A431 cells in vitro, further in vivo studies are required to determine
      whether berberine could be an effective chemotherapeutic agent for the management
      of non-melanoma skin cancers.

PMID- 16621887
TI  - Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous
      melanoma.
AB  - Sunlight causes various kinds of DNA damage, including oxidative lesions that are
      removed effectively by the base excision repair (BER) pathway, in which ADPRT,
      XRCC1 and APE1 play a key role. However, genetic variation in these genes may
      alter their functions. We hypothesized that ADPRT, XRCC1 and APE1 polymorphisms
      are associated with risk of cutaneous melanoma (CM). In a hospital-based case
      control study of 602 CM patients and 603 cancer-free control subjects frequency
      matched on age, sex and ethnicity, we genotyped for three non-synonymous single
      nucleotide polymorphisms (SNPs) (i.e. the ADPRT Val762Ala, XRCC1 Arg399Gln and
      APE1Asp148Glu) and assessed their associations with risk of CM. We found no
      significant difference in the allele frequencies between cases and controls for
      any of these three SNPs. However, we found that, compared with the APE1 Asp/Asp
      genotype, a significantly decreased risk of CM was associated with the APE1
      Asp/Glu [adjusted odds ratio (OR), 0.60; 95% confidence interval (CI), 0.41
      0.86], Glu/Glu (OR, 0.58; 95% CI, 0.38-0.88) and combined APE1 Asp/Glu+Glu/Glu
      (OR, 0.59; 95% CI, 0.42-0.83) genotypes, but not for other XRCC1 variant
      genotypes. Moreover, there was evidence for a possible gene-gene interaction
      between XRCC1 and APE1 variants in the association with risk of CM (P=0.030). We
      conclude that the APE1 Glu variant may have an effect or interact with XRCC1 in
      the etiology of CM or in linkage disequilibrium with other untyped protective
      alleles. Larger studies with more SNPs in the BER genes are needed to verify
      these findings.

PMID- 16621888
TI  - The thermogenic center in social wasps.
AB  - In the social wasps Vespa orientalis and Paravespula germanica (Hymenoptera,
      Vespinae), a thermogenic center has been found in the dorsal part of the first
      thoracic segment. The temperature in this region of the prothorax is higher by 6
      9 degrees C than that at the tip of the abdomen, and this in actively flying
      hornets outside the nest (workers, males or queens) as well as in hornets inside
      the nest that attend to the brood in the combs. On viewing the region from the
      outside, one discerns a canal or rather a fissure in the cuticle, which commences
      at the center of the dorsal surface of the prothorax and extends till the
      mesothorax. Thus the length of this canal or fissure is approximately 5-7 mm and
      it is seen to contain numerous thin hairs whose shape varies from that of the
      hairs alongside the structure. Beneath the cuticle in this region there are
      dorsoventral as well as longitudinal muscles in abundance, much the same as the
      musculature in the remaining thoracic segments (i.e. the meso- and metathorax),
      which activate the two pairs of wings. The canal-bearing segment is of course
      devoid of wings, and its dorsoventral muscles are attached to the cuticle, which
      in this region resembles a bowl harboring several layers of epithelium that
      boasts numerous butterfly-shaped tracheal branches. Additionally there are layers
      that display lymph-filled spaces and also perforated layers and depressions, and
      beneath all these is a lace-like layer that also coats the cuticle's hollows.
      Underneath the cuticle proper, there are numerous large mitochondria and
      tracheae, which occupy a considerable part of the cuticular epithelium surface.
      These abundant mitochondria are, most probably, the main element of heat
      production in the thermogenic center.

PMID- 16621889
TI  - Transcriptional profile reveals altered hepatic lipid and cholesterol metabolism
      in hyposulfatemic NaS1 null mice.
AB  - Sulfate plays an essential role in human growth and development, and its
      circulating levels are maintained by the renal Na+-SO42- cotransporter, NaS1. We
      previously generated a NaS1 knockout (Nas1-/-) mouse, an animal model for
      hyposulfatemia, that exhibits reduced growth and liver abnormalities including
      hepatomegaly. In this study, we investigated the hepatic gene expression profile
      of Nas1-/- mice using oligonucleotide microarrays. The mRNA expression levels of
      92 genes with known functional roles in metabolism, cell signaling, cell defense,
      immune response, cell structure, transcription, or protein synthesis were
      increased (n = 51) or decreased (n = 41) in Nas1-/- mice when compared with
      Nas1+/+ mice. The most upregulated transcript levels in Nas1-/- mice were found
      for the sulfotransferase genes, Sult3a1 (approximately 500% increase) and Sult2a2
      (100% increase), whereas the metallothionein-1 gene, Mt1, was among the most
      downregulated genes (70% decrease). Several genes involved in lipid and
      cholesterol metabolism, including Scd1, Acly, Gpam, Elov16, Acsl5, Mvd, Insig1,
      and Apoa4, were found to be upregulated (> or = 30% increase) in Nas1-/- mice. In
      addition, Nas1-/- mice exhibited increased levels of hepatic lipid (approximately
      16% increase), serum cholesterol (approximately 20% increase), and low-density
      lipoprotein (approximately 100% increase) and reduced hepatic glycogen
      (approximately 50% decrease) levels. In conclusion, these data suggest an altered
      lipid and cholesterol metabolism in the hyposulfatemic Nas1-/- mouse and provide
      new insights into the metabolic state of the liver in Nas1-/- mice.

PMID- 16621890
TI  - An unconventional dileucine-based motif and a novel cytosolic motif are required
      for the lysosomal and melanosomal targeting of OA1.
AB  - The protein product of the gene responsible for ocular albinism type 1, named
      OA1, is a pigment-cell-specific membrane glycoprotein, displaying features of G
      protein-coupled receptors, yet exclusively localized to late endosomes, lysosomes
      and melanosomes. To dissect the signals responsible for the intracellular
      localization of OA1, we generated chimeric proteins consisting of the cytosolic
      domains of OA1 fused to the lumenal and transmembrane domains of LAMP1; in
      addition, we generated missense and deletion mutants of full-length OA1. Using
      this approach, we identified two separate sorting signals that are both necessary
      and sufficient for intracellular retention, as well as lysosomal and melanosomal
      localization, in melanocytic and non-melanocytic cells. These sorting signals are
      an unconventional dileucine motif within the third cytosolic loop and a novel
      motif, characterized by a tryptophan-glutamic acid doublet, within the C-terminal
      tail. Both motifs must be mutated to promote the plasma membrane localization of
      OA1, suggesting that they can independently drive its intracellular targeting. In
      addition, both motifs act similarly as lysosomal sorting signals in non
      melanocytic cells, but appear to carry different specificities in melanocytic
      cells. Our findings indicate that OA1 contains multiple unconventional signals
      responsible for its lysosomal and melanosomal localization, and reveal a
      remarkable and unforeseen complexity in the regulation of polytopic protein
      sorting to specialized secretory organelles.

PMID- 16621891
TI  - Rac1 signalling in the Drosophila larval cellular immune response.
AB  - The Drosophila larval cellular immune response involves cells (hemocytes) that
      can be recruited from a hematopoietic organ located behind the brain, as well as
      a sessile population of cells found just underneath the larval cuticle arranged
      in a segmental pattern. By using two Rac1 GTPase effector-loop mutants together
      with epistasis studies, we show that Rac1 requires the Drosophila melanogaster
      Jun N-terminal kinase Basket (Bsk), as well as stable actin formation to recruit
      the sessile hemocyte population. We show that actin stabilization is necessary
      for Rac1-induced hemocyte activation by lowering cofilin (encoded by the twinstar
      gene tsr) expression in blood cells. Removing Bsk by RNAi suppressed Rac1-induced
      release of sessile hemocytes. RNAi against Bsk also suppressed Rac1 induction of
      lamellocytes, a specialized population of hemocytes necessary for the
      encapsulation of invading pathogens. Furthermore, Rac1 and Bsk are involved in
      regulating the formation of actin- and focal adhesion kinase (FAK)-rich placodes
      in hemocytes. Lastly, Rac1 and Bsk are both required for the proper encapsulation
      of eggs from the parasitoid wasp Leptipolina boulardi. From these data we
      conclude that Rac1 induces Bsk activity and stable actin formation for cellular
      immune activation, leading to sessile hemocyte release and an increase in the
      number of circulating hemocytes.

PMID- 16621892
TI  - Inefficient reprogramming of the hematopoietic stem cell genome following nuclear
      transfer.
AB  - In general, cloning undifferentiated preimplantation embryos (blastomeres) or
      embryonic stem cells is more efficient than cloning differentiated somatic cells.
      Therefore, there has been an assumption that tissue-specific stem cells might
      serve as efficient donors for nuclear transfer because of the undifferentiated
      state of their genome. Here, we show that this is not the case with adult
      hematopoietic stem cells (HSCs). Although we have demonstrated for the first time
      that mouse HSCs can be cloned to generate offspring, the birth rates (0-0.7%)
      were lowest among the clones tested (cumulus, immature Sertoli and fibroblast
      cells). Only 6% of reconstructed embryos reached the morula or blastocyst stage
      in vitro (versus 46% for cumulus clones; P < 5 x 10(-10)). Transcription and gene
      expression analyses of HSC clone embryos revealed that they initiated zygotic
      gene activation (ZGA) at the appropriate timing, but failed to activate five out
      of six important embryonic genes examined, including Hdac1 (encoding histone
      deacetylase 1), a key regulator of subsequent ZGA. These results suggest that the
      HSC genome has less plasticity than we imagined, at least in terms of
      reprogrammability in the ooplasm after nuclear transfer.

PMID- 16621893
TI  - Downstream regulatory element antagonistic modulator regulates islet prodynorphin
      expression.
AB  - Calcium-binding proteins regulate transcription and secretion of pancreatic islet
      hormones. Here, we demonstrate neuroendocrine expression of the calcium-binding
      downstream regulatory element antagonistic modulator (DREAM) and its role in
      glucose-dependent regulation of prodynorphin (PDN) expression. DREAM is
      distributed throughout beta- and alpha-cells in both the nucleus and cytoplasm.
      As DREAM regulates neuronal dynorphin expression, we determined whether this
      pathway is affected in DREAM(-/-) islets. Under low glucose conditions, with
      intracellular calcium concentrations of <100 nM, DREAM(-/-) islets had an 80%
      increase in PDN message compared with controls. Accordingly, DREAM interacts with
      the PDN promoter downstream regulatory element (DRE) under low calcium (<100 nM)
      conditions, inhibiting PDN transcription in beta-cells. Furthermore, beta-cells
      treated with high glucose (20 mM) show increased cytoplasmic calcium
      (approximately 200 nM), which eliminates DREAM's interaction with the DRE,
      causing increased PDN promoter activity. As PDN is cleaved into dynorphin
      peptides, which stimulate kappa-opioid receptors expressed predominantly in alpha
      cells of the islet, we determined the role of dynorphin A-(1-17) in glucagon
      secretion from the alpha-cell. Stimulation with dynorphin A-(1-17) caused alpha
      cell calcium fluctuations and a significant increase in glucagon release. DREAM(
      /-) islets also show elevated glucagon secretion in low glucose compared with
      controls. These results demonstrate that PDN transcription is regulated by DREAM
      in a calcium-dependent manner and suggest a role for dynorphin regulation of
      alpha-cell glucagon secretion. The data provide a molecular basis for opiate
      stimulation of glucagon secretion first observed over 25 years ago.

PMID- 16621894
TI  - Ovarian suppression with gonadotropin-releasing hormone agonist reduces whole
      body protein turnover in women.
AB  - The age-related decline in fat-free mass is accelerated in women after menopause.
      The role of ovarian hormone deficiency in the regulation of fat-free mass,
      however, has not been clearly defined. To address this question, we examined the
      effect of ovarian hormone suppression on whole body protein metabolism. Whole
      body protein breakdown, oxidation, and synthesis were measured using
      [(13)C]leucine in young, healthy women with regular menstrual patterns before and
      after 2 mo of treatment with gonadotropin-releasing hormone agonist (GnRHa; n =
      6) or placebo (n = 7). Protein metabolism was measured under postabsorptive and
      euglycemic-hyperinsulinemic-hyperaminoacidemic conditions. Ovarian suppression
      did not alter whole body or regional fat-free mass or adiposity. In the
      postabsorptive state, GnRHa administration was associated with reductions in
      protein breakdown and synthesis (P < 0.05), whereas no change in protein
      oxidation was noted. Under euglycemic-hyperinsulinemic-hyperaminoacidemic
      conditions, a similar reduction (P < 0.05) in protein synthesis and breakdown was
      noted, whereas, protein oxidation increased (P < 0.05) in the placebo group.
      Testosterone, steroid hormone precursors, insulin-like growth factor I, and their
      respective binding proteins were not altered by GnRHa administration, and changes
      in these hormones over time were not associated with GnRHa-induced alterations in
      protein metabolism, suggesting that changes in protein turnover are not due to an
      effect of ovarian suppression on other endocrine systems. Our findings provide
      evidence that endogenous ovarian hormones participate in the regulation of
      protein turnover in women.

PMID- 16621895
TI  - Growth hormone receptor gene deficiency causes delayed insulin responsiveness in
      skeletal muscles without affecting compensatory islet cell overgrowth in obese
      mice.
AB  - Growth hormone (GH), acting through its receptor (GHR), is essential for somatic
      growth and development and maintaining metabolic homeostasis. GHR gene-deficient
      (GHR(-/-)) mice exhibit drastically diminished insulin-like growth factor-I (IGF
      I) levels, proportional growth retardation, elevated insulin sensitivity, and
      reduced islet beta-cell mass. Unlike the liver, which is mostly unaffected by
      changes in IGF-I level, skeletal muscles express high levels of IGF-I receptor
      (IGF-IR). The net result of a concurrent deficiency in the actions of both GH and
      IGF-I, which exert opposite influences on insulin responsiveness, has not been
      evaluated. We studied insulin-stimulated early responses in the insulin receptor
      (IR), insulin receptor substrate-1 (IRS-1), and p85 subunit of
      phosphatidylinositol 3-kinase. Upon in vivo insulin stimulation, skeletal muscles
      of GHR(-/-) mice exhibit transient delayed responses in IR and IRS-1
      phosphorylation but normal levels of p85 association with IRS-1. This is in
      contrast to normal/elevated insulin responses in hepatocytes and indicates tissue
      specific effects of GHR gene deficiency. In addition to stimulating normal islet
      cell growth, GH may participate in islet cell overgrowth, which compensates for
      insulin resistance induced by obesity. To determine whether the islet cell
      overgrowth is dependent on GH signaling, we studied the response of male GHR(-/-)
      mice to high-fat diet (HFD)-induced obesity. After 17 wk on a HFD, GHR(-/-) mice
      became more significantly obese than wild-type mice and exhibited increased beta
      cell mass to a slightly higher extent. These data demonstrate that GH signaling
      is not required for compensatory islet growth. Thus, in both muscle insulin
      responsiveness and islet growth compensation, normal levels of GH signals do not
      seem to play a dominant role.

PMID- 16621896
TI  - Cortisol stimulates system A amino acid transport and SNAT2 expression in a human
      placental cell line (BeWo).
AB  - Both placental system A activity and fetal plasma cortisol concentrations are
      associated with intrauterine growth retardation, but it is not known if these
      factors are mechanistically related. Previous functional studies using hepatoma
      cells and fibroblasts produced conflicting results regarding the regulation of
      system A by cortisol. Using the b30 BeWo choriocarcinoma cell line, we
      investigated the regulation of system A by cortisol. System A function was
      analyzed using methyl amino isobutyric acid (MeAIB) transcellular transport
      studies. Transporter expression [system A transporter (SNAT)1/2] was studied at
      the mRNA and protein levels using Northern and Western blotting, respectively.
      Localization was carried out using immunocytochemistry. The [(14)C]MeAIB transfer
      rate across BeWo monolayers after preincubation with cortisol for 24 h was
      significantly increased compared with control. This was associated with a
      relocalization of the SNAT2 transporter at lower cortisol levels and significant
      upregulation of mRNA and protein expression levels at cortisol levels >1 microM.
      This is the first study to show functional and molecular regulation of system A
      by cortisol in BeWo cells. It is also the first study to identify which system A
      isoform is regulated. These results suggest that cortisol may be involved in
      upregulation of system A in the placenta to ensure sufficient amino acid supply
      to the developing fetus.

PMID- 16621897
TI  - Influence of intensity of food restriction on skeletal muscle mitochondrial
      energy metabolism in rats.
AB  - Variable durations of food restriction (FR; lasting weeks to years) and variable
      FR intensities are applied to animals in life span-prolonging studies. A
      reduction in mitochondrial proton leak is suggested as a putative mechanism
      linking such diet interventions and aging retardation. Early mechanisms of
      mitochondrial metabolic adaptation induced by FR remain unclear. We investigated
      the influence of different degrees of FR over 3 days on mitochondrial proton leak
      and mitochondrial energy metabolism in rat hindlimb skeletal muscle. Animals
      underwent 25, 50, and 75% and total FR compared with control rats. Proton leak
      kinetics and mitochondrial functions were investigated in two mitochondrial
      subpopulations, intermyofibrillar (IMF) and subsarcolemmal (SSM) mitochondria.
      Regardless of the degree of restriction, skeletal muscle mass was not affected by
      3 days of FR. Mitochondrial basal proton conductance was significantly decreased
      in 50% restricted rats in both mitochondrial subpopulations (46 and 40% for IMF
      and SSM, respectively) but was unaffected in other groups compared with controls.
      State 3 and uncoupled state 3 respiration rates were decreased in SSM
      mitochondria only for 50% restricted rats when pyruvate + malate was used as
      substrate (-34.5 and -38.9% compared with controls, P < 0.05). IMF mitochondria
      respiratory rates remained unchanged. Three days of FR, particularly at 50% FR,
      were sufficient to lower mitochondria energetic metabolism in both mitochondrial
      populations. Our study highlights an early step in mitochondrial adaptation to FR
      and the influence of the severity of restriction on this adaptation. This step
      may be involved in an aging-retardation process.

PMID- 16621898
TI  - Perturbation of glucose flux in the liver by decreasing F26P2 levels causes
      hepatic insulin resistance and hyperglycemia.
AB  - Hepatic insulin resistance is one of the characteristics of type 2 diabetes and
      contributes to the development of hyperglycemia. How changes in hepatic glucose
      flux lead to insulin resistance is not clearly defined. We determined the effects
      of decreasing the levels of hepatic fructose 2,6-bisphosphate (F26P(2)), a key
      regulator of glucose metabolism, on hepatic glucose flux in the normal 129J mice.
      Upon adenoviral overexpression of a kinase activity-deficient 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase, the enzyme that determines F26P(2) level,
      hepatic F26P(2) levels were decreased twofold compared with those of control
      virus-treated mice in basal state. In addition, under hyperinsulinemic
      conditions, hepatic F26P(2) levels were much lower than those of the control. The
      decrease in F26P(2) leads to the elevation of basal and insulin-suppressed
      hepatic glucose production. Also, the efficiency of insulin to suppress hepatic
      glucose production was decreased (63.3 vs. 95.5% suppression of the control). At
      the molecular level, a decrease in insulin-stimulated Akt phosphorylation was
      consistent with hepatic insulin resistance. In the low hepatic F26P(2) states,
      increases in both gluconeogenesis and glycogenolysis in the liver are responsible
      for elevations of hepatic glucose production and thereby contribute to the
      development of hyperglycemia. Additionally, the increased hepatic gluconeogenesis
      was associated with the elevated mRNA levels of peroxisome proliferator-activated
      receptor-gamma coactivator-1alpha and phosphoenolpyruvate carboxykinase. This
      study provides the first in vivo demonstration showing that decreasing hepatic
      F26P(2) levels leads to increased gluconeogenesis in the liver. Taken together,
      the present study demonstrates that perturbation of glucose flux in the liver
      plays a predominant role in the development of a diabetic phenotype, as
      characterized by hepatic insulin resistance.

PMID- 16621899
TI  - Systemic administration of IGF-I enhances oxidative status and reduces
      contraction-induced injury in skeletal muscles of mdx dystrophic mice.
AB  - The absence of dystrophin and resultant disruption of the dystrophin glycoprotein
      complex renders skeletal muscles of dystrophic patients and dystrophic mdx mice
      susceptible to contraction-induced injury. Strategies to reduce contraction
      induced injury are of critical importance, because this mode of damage
      contributes to the etiology of myofiber breakdown in the dystrophic pathology.
      Transgenic overexpression of insulin-like growth factor-I (IGF-I) causes myofiber
      hypertrophy, increases force production, and can improve the dystrophic pathology
      in mdx mice. In contrast, the predominant effect of continuous exogenous
      administration of IGF-I to mdx mice at a low dose (1.0-1.5 mg.kg(-1).day(-1)) is
      a shift in muscle phenotype from fast glycolytic toward a more oxidative, fatigue
      resistant, slow muscle without alterations in myofiber cross-sectional area,
      muscle mass, or maximum force-producing capacity. We found that exogenous
      administration of IGF-I to mdx mice increased myofiber succinate dehydrogenase
      activity, shifted the overall myosin heavy chain isoform composition toward a
      slower phenotype, and, most importantly, reduced contraction-induced damage in
      tibialis anterior muscles. The deficit in force-producing capacity after two
      damaging lengthening contractions was reduced significantly in tibialis anterior
      muscles of IGF-I-treated (53 +/- 4%) compared with untreated mdx mice (70 +/- 5%,
      P < 0.05). The results provide further evidence that IGF-I administration can
      enhance the functional properties of dystrophic skeletal muscle and, compared
      with results in transgenic mice or virus-mediated overexpression, highlight the
      disparities in different models of endocrine factor delivery.

PMID- 16621900
TI  - Continuous testosterone administration prevents skeletal muscle atrophy and
      enhances resistance to fatigue in orchidectomized male mice.
AB  - Androgens promote anabolism in skeletal muscle; however, effects on subsequent
      muscle function are less well defined because of a lack of reliable experimental
      models. We established a rigorous model of androgen withdrawal and administration
      in male mice and assessed androgen regulation of muscle mass, structure, and
      function. Adult C57Bl/6J male mice were orchidectomized (Orx) or sham-operated
      (Sham) and received 10 wk of continuous testosterone (T) or control treatment (C)
      via intraperitoneal implants. Mass, fiber cross-sectional area (CSA), and in
      vitro contractile function were assessed for fast-twitch extensor digitorum
      longus (EDL) and slow-twitch soleus (SOL) muscles. After 10 wk, Orx+C mice had
      reduced body weight gain (P < 0.05), seminal vesicle mass (P < 0.01), and levator
      ani muscle mass (P < 0.001) compared with Sham+C mice, and these effects were
      prevented with testosterone treatment. Orx+T mice had greater EDL (P < 0.01) and
      SOL (P < 0.01) muscle mass compared with Orx+C mice; however, median fiber CSA
      was not significantly altered in these muscles. EDL and SOL muscle force was
      greater in Sham+T compared with Orx+C mice (P < 0.05) in proportion to muscle
      mass. Unexpectedly, Orx+T mice had increased fatigue resistance of SOL muscle
      compared with Orx+C mice (P < 0.001). We used a rigorous model of androgen
      withdrawal and administration in male mice to demonstrate an essential role of
      androgens in the maintenance of muscle mass and force. In addition, we showed
      that testosterone treatment increases resistance to fatigue of slow- but not fast
      twitch muscle.

PMID- 16621901
TI  - Use of [18F]fluorodeoxyglucose positron emission tomography in evaluating locally
      recurrent and metastatic adrenocortical carcinoma.
AB  - CONTEXT: Adrenocortical carcinomas are uncommon, and their evaluation by
      [(18)F]fluorodeoxyglucose positron emission tomography (FDG PET) has not been
      well evaluated. OBJECTIVE: The purpose of this study was to examine the potential
      utility of FDG PET in the detection of recurrent or metastatic adrenocortical
      carcinoma. DESIGN: In patients with known adrenocortical carcinoma who underwent
      FDG-PET imaging for suspected recurrence or metastasis, FDG activity was compared
      with other imaging findings, clinical features, and the presence or absence of
      disease as confirmed by resection, biopsy, or clinical follow-up. SETTING: The
      study took place at four tertiary referral centers. PATIENTS OR OTHER
      PARTICIPANTS: Twelve patients (10 females and two males, 5-71 yr of age) were
      evaluated. MAIN OUTCOME MEASURES: The main outcome measures were FDG activity,
      other imaging findings, and clinical features. RESULTS: Abnormal FDG uptake
      correctly indicated tumor recurrence in 10 patients. One patient with no abnormal
      FDG activity had a morphological abnormality subsequently proven to be a
      postoperative scar. Two patients, one with very small pulmonary lesions and one
      with a hepatic metastasis, had false-negative findings. CONCLUSIONS: Most
      adrenocortical carcinomas accumulate and retain FDG and thus can be visualized by
      PET. However, false-negative findings are possible, especially with very small
      lesions.

PMID- 16621902
TI  - Insulin differentially regulates monocyte and polymorphonuclear neutrophil
      functions in healthy young and elderly humans.
AB  - CONTEXT: Insulin can regulate immune cell function. Aging is associated with
      various degrees of insulin resistance together with reduced immune cell activity.
      OBJECTIVE: We investigated the hypothesis that blood monocytes and
      polymorphonuclear neutrophils (PMNs) are less responsive to the action of insulin
      in elderly subjects. DESIGN-INTERVENTION: We evaluated the effect of
      hyperinsulinemia (0.7 mU/kg(-1) fat-free mass per minute(-1)) on monocyte and PMN
      activity using a 4-h euglycemic clamp technique. PARTICIPANTS: Eight young (24 +/
      6 yr old) and nine elderly (69 +/- 4 yr old) healthy volunteers participated in
      the study. MAIN OUTCOME MEASURES: Monocyte and PMN receptor expression and
      density were measured using flow cytometric detection. PMN chemotaxis toward
      formyl-Met-Leu-Phe (fMLP) was evaluated using a two-compartment chamber. PMN and
      monocyte phagocytosis was determined by measuring the engulfment of opsonized
      particles. Microbicidal functions were determined based on the production of
      reactive oxygen species (ROS) and bactericidal protein by stimulated cells.
      RESULTS: The density of PMN and monocyte insulin receptors was not affected by
      age or insulin clamp treatment regardless of the age. Insulin was able to
      regulate the expression of receptors involved in PMN action in the young-adult
      group only. PMN chemotaxis was up-regulated by insulin in both groups. In
      contrast, although insulin stimulated phagocytosis and bactericidal activity in
      young-adult subjects, the ability of PMN to adapt to physiological
      hyperinsulinemia was blunted in the older group. The effect of insulin on
      monocyte bactericidal properties seemed to be limited, although a suppressive
      action on fMLP-induced ROS production was detected in young adults. CONCLUSIONS:
      We confirmed the presence of the insulin receptor on monocyte and PMN membranes.
      We revealed that insulin has a limited action on monocyte function. Insulin has a
      priming effect on the main PMN functions. Immune cell function adapted poorly to
      insulin infusion in the elderly subjects.

PMID- 16621903
TI  - Clinicopathological significance of major histocompatibility complex class I
      related chain a and B expression in thyroid cancer.
AB  - CONTEXT: Major histocompatibility complex class I-related chains A and B (MICA/B)
      are two stress-inducible ligands for the immunoreceptor NKG2D that is expressed
      on cytotoxic T cells and natural killer (NK) cells. It is not known whether
      MICA/B expression is up-regulated in thyroid cancer as a result of oncogene
      activation. OBJECTIVE: The objective of the investigation was to study MICA/B
      expression and regulation in thyroid cancer and its role in mediating the
      cytotoxicity of NK cells. METHODS: MICA/B expression in thyroid cancer was
      analyzed by immunohistochemical staining. Cell surface MICA/B levels in thyroid
      tumor cell lines and fresh tumor cells were analyzed by flow cytometric analysis.
      The susceptibility of thyroid tumor cells to NK cell killing was tested by using
      (51)Cr release assay. RESULTS: MICA/B was expressed at moderate or high levels in
      18 of 39 papillary thyroid carcinomas and four of eight anaplastic thyroid
      carcinomas. MICA/B expression was confirmed by flow cytometric analysis in three
      fresh thyroid neoplasms. MICA/B expression was detected in eight of 10 thyroid
      tumor cell lines and correlated with their sensitivity to killing by the NKG2/D
      positive NK-92 cells. Blocking of NKG2D and MICA/B interaction by specific
      antibodies partially led to the inhibition of NK-92 cell-mediated cytotoxicity.
      The MAPK inhibitors were able to block MICA/B expression in MRO87 and HeLa cells.
      Transient transfection of mutant BRAF and RAS oncogenes led to increased MICA/B
      expression in 293 cells and WRO82 cells. CONCLUSION: MICA/B expression is up
      regulated in thyroid cancer, probably due to the activation of the MAPK pathway.
      MICA/B in thyroid cancer plays an important role in NK-92 cell-mediated
      cytotoxicity.

PMID- 16621904
TI  - Adipose tissue stimulates bone growth in prepubertal children.
AB  - CONTEXT: Fat mass represents a positive influence on bone mass in adults,
      independently of other factors such as lean mass, but whether a similar action
      occurs in children is unclear. OBJECTIVE: Our objective was to examine the
      relationship between fat mass and bone mass in children. DESIGN AND SETTING: We
      conducted combined cross-sectional and prospective analyses at university
      research clinics. PARTICIPANTS: Participants included children aged 9.9 yr from a
      large population-based birth cohort in southwest England. OUTCOMES: Relationships
      between total body fat mass were measured by dual-energy x-ray absorptiometry at
      age 9.9 yr, and 1) total-body-less-head bone mass and area at age 9.9 and 2)
      increase in bone mass and area over the following 2 yr. RESULTS: There was a
      strong positive relationship between total body fat mass and total-body-less-head
      bone mass and area, even after adjustment for height and/or lean mass (P <
      0.001). There was a similar positive association between total body fat mass and
      increase in bone mass and area over the following 2 yr in boys and Tanner stage 1
      girls. In contrast, no association was present between fat mass and gain in bone
      mass and size in Tanner stage 2 girls, whereas a negative association was seen in
      Tanner stage 3 girls (puberty-fat mass interaction, P < 0.001). CONCLUSIONS: In
      prepubertal children, fat mass is a positive independent determinant of bone mass
      and size and of increases in these parameters over the following 2 yr, suggesting
      that adipose tissue acts to stimulate bone growth. However, this relationship is
      attenuated by puberty.

PMID- 16621905
TI  - Diencephalic syndrome due to hypothalamic tumor: a model of the relationship
      between weight and puberty onset.
AB  - CONTEXT: Changes in body weight, statural growth rate, and puberty may be the
      presenting symptoms of hypothalamic-pituitary tumors. OBJECTIVE: The objective of
      the study was to assess the relationship between the tumor and its treatment and
      the weight, growth rate, and onset of puberty, using the diencephalic syndrome of
      emaciation as model. PATIENTS: Eleven patients seen before 1 yr of age, except
      one aged 9 yr, for diencephalic syndrome of emaciation due to hypothalamic
      pilocytic astrocytoma, were treated by surgical resection (n = 9), cranial
      irradiation (n = 7), and/or chemotherapy (n = 10). RESULTS: At diagnosis, growth
      rate was normal, despite the emaciation, and there was no hypothalamic-pituitary
      deficiency, except in the oldest patient. After tumor treatment, all had GH and
      thyroid-stimulating hormone deficiencies, but only three, who underwent major
      surgical resection, also had ACTH deficiency and diabetes insipidus. Eight became
      obese, and all but the oldest had transient precocious puberty. Plasma leptin
      concentrations were very low at diagnosis, increased after tumor treatment, and
      decreased transiently in one boy when the testosterone increased. The plasma
      soluble leptin receptor concentrations changed in the opposite direction, leading
      to an increase in the free leptin index, including in the three patients whose
      tumor was reduced without surgery. The body mass index was correlated positively
      with plasma leptin (rho = 0.73, P = 0.0004) and free leptin index (rho = 0.63, P
      < 0.004) and negatively with ghrelin (rho = -0.49, P < 0.03) concentrations.
      CONCLUSIONS: The obesity that occurs after treatment of hypothalamic tumors is
      not due to dysregulation of leptin secretion because it and plasma soluble leptin
      receptor remain regulated by factors like testosterone. This study also shows the
      influence of weight, possibly via leptin secretion, on the transient hypothalamic
      pituitary-gonadal activation that occurs during the first year of life.

PMID- 16621906
TI  - Direct effect of progestogen on gene expression in the testis during gonadotropin
      withdrawal and early suppression of spermatogenesis.
AB  - CONTEXT: Testicular production of steroids and gametes is under gonadotropin
      support, but there is little information as to the molecular mechanisms by which
      these are regulated in the human. The testicular response to gonadotropin
      withdrawal is important for the development of effective contraceptive methods.
      OBJECTIVE: Our objective was investigation of expression of genes in the normal
      human testis reflecting steroidogenesis, Sertoli cell function, and
      spermatogenesis after short-term gonadotropin withdrawal and the effects of
      activating testicular progesterone receptors. DESIGN AND SETTING: We conducted a
      randomized controlled trial at a research institute. PATIENTS: Thirty healthy men
      participated. INTERVENTIONS: Subjects were randomized to no treatment or
      gonadotropin suppression by GnRH antagonist (cetrorelix) with testosterone (CT
      group) or with additional administration of the gestogen desogestrel (CTD group)
      for 4 wk before testicular biopsy. Gene expression was quantified by RT-PCR.
      RESULTS: Both treatment groups showed similar suppression of gonadotropins and
      sperm production and markedly reduced expression of steroidogenic enzymes.
      Addition of progestogen in the CTD group resulted in reduced expression of 5alpha
      reductase type 1 compared with both controls and the CT group. Inhibin-alpha and
      the spermatocyte marker acrosin-binding protein were significantly lower in the
      CTD but not CT groups, compared with controls, but did not differ between treated
      groups. Men who showed greater falls in sperm production also showed reduced
      expression of these three genes but not of the spermatid marker protamine 1.
      CONCLUSIONS: These data provide evidence for direct progestogenic effects on the
      testis and highlight steroid 5alpha-reduction and disruption of spermiation as
      important components of the testicular response to gonadotropin withdrawal.

PMID- 16621907
TI  - Antipituitary antibodies recognizing growth hormone (GH)-producing cells in
      children with idiopathic GH deficiency and in children with idiopathic short
      stature.
AB  - CONTEXT: Antipituitary antibodies (APA) recognizing GH-secreting cells may
      indicate an autoimmune pituitary involvement in adults with idiopathic GH
      deficiency (IGHD). OBJECTIVE: We aimed 1) to investigate the presence of APA in
      prepubertal children with IGHD or idiopathic short stature (ISS), identifying the
      pituitary hormone-producing cells targeted by APA; and 2) to verify whether in
      patients with ISS the presence of APA could predict the development of GHD.
      DESIGN: We performed a cross-sectional and partially longitudinal cohort study.
      SETTING: The study was performed at the Endocrinology Unit and Pediatric Unit of
      the Second University and University Federico II of Naples, respectively.
      PATIENTS: Twenty-six children with IGHD (group 1), 60 children with ISS (group
      2), 33 children with GHD caused by lesions/abnormalities of the hypothalamus or
      pituitary (group 3), and 40 controls participated in the study. Nineteen children
      of group 2 were reevaluated after 2 yr. MAIN OUTCOME MEASURES: IGF-I levels, GH
      secretion, and APA (by indirect immunofluorescence) were evaluated in all
      participants. RESULTS: At study entry, APA recognizing GH-producing cells were
      detected in seven of 26 children in group 1 and in 14 of 60 in group 2. Two years
      later, all eight initially APA-positive and all 11 APA-negative of the 19
      reevaluated patients persisted positive and negative, respectively. The
      reevaluation of GH secretion in these patients revealed the development of GHD in
      all but one of the APA-positive children but in none of the APA-negative ones.
      CONCLUSIONS: IGHD in children can be frequently associated with APA targeting GH
      secreting cells; thus, the detection of APA in children with ISS could identify
      those prone to develop GHD.

PMID- 16621908
TI  - Prolactin deficiency is independently associated with reduced insulin-like growth
      factor I status in severely growth hormone-deficient adults.
AB  - BACKGROUND: In adult life, considerable overlap in IGF-I status exists between
      normal and severely GH-deficient (GHD) subjects defined by conventional dynamic
      testing of GH secretion. IGF-I is not therefore widely viewed as a reliable
      diagnostic marker for GHD. Recognized factors influencing serum IGF-I level in
      GHD include age, gender, timing of onset of GHD, and exogenous estrogen therapy,
      but these do not fully explain GH/IGF-I discordance in severe GHD. The primary
      structures of prolactin and GH are closely related. Effects of hypoprolactinemia
      are not well described in humans, but laboratory studies suggest a role for
      prolactin in hepatic IGF-I release, possibly through a signal transducer and
      activator of transcription 5 (STAT5) pathway. The purpose of this study was to
      evaluate a potential contribution of prolactin to IGF-I status in severely GHD
      adults. PATIENTS AND METHODS: Using multiple regression analysis techniques,
      contributions of the following variables to age-adjusted IGF-I sd scores were
      evaluated in 162 (85 female) GHD adults: gender, timing of onset of GHD, presence
      or absence of prolactin deficiency, body mass index, number of additional
      pituitary deficits, and underlying pathology. RESULTS: Childhood onset GHD (P <
      0.0001) and presence of prolactin deficiency (P < 0.0001) were independently
      associated with reduced IGF-I status. The contributions of these parameters to
      IGF-I sd scores were -2.55 and -2.67, respectively. Gender (P = 0.06), body mass
      index (P = 0.99), number of additional pituitary deficits (P = 0.64), and
      underlying pathology (P = 0.06) did not significantly influence IGF-I status.
      CONCLUSIONS: Prolactin deficiency is independently associated with reduced IGF-I
      status in hypopituitary adults. It is possible that prolactin deficiency is a
      surrogate for the degree of severity of GHD, implying a GHD paradigm undetected
      by conventional GH provocative tests; alternatively, it remains plausible that
      circulating prolactin contributes to IGF-I release in the absence of GH, possibly
      through a signal transducer and activator of transcription 5 (STAT5) pathway.

PMID- 16621909
TI  - Use of organ culture to study the human fetal testis development: effect of
      retinoic acid.
AB  - CONTEXT: In human, the chronology of the testicular development has been
      extensively studied, but the factors implicated in the onset and the regulation
      of gametogenesis and steroidogenesis remain hardly known. OBJECTIVES: To identify
      these factors, we developed an organ culture system for human fetal testes
      recovered during the first trimester (6-12 wk) of gestation. We first aimed at
      investigating the characteristics of this system by comparing the in vivo and in
      vitro gametogenesis and steroidogenesis. Second, we used organ culture to
      investigate the effect on the human testicular functions of retinoic acid (RA),
      previously described as a regulator of gonadal development in rodents. RESULTS:
      Organ culture proved to be an efficient tool for studying the early development
      of the testicular functions. Indeed, this system was able to maintain
      satisfactory development of the germ cells and Leydig cells in the absence of any
      added factor. For older fetuses, the number of germ cells decreased in culture
      and the LH was necessary to maintain the steroidogenic activity. The addition of
      10(-6) m RA decreased the total number of germ cells in the fetal testis at all
      studied stages. This resulted from an increase in apoptosis, which slightly
      exceeded the increase of proliferation. However, RA had a stimulatory effect on
      the steroidogenic function for the youngest fetuses over a short period of time
      by increasing the expression of P450 cholesterol side-chain cleavage, 17 alpha
      hydroxylase/C17-20 lyase, and steroidogenic acute regulatory protein.
      CONCLUSIONS: Thus, RA appears as a potential regulator of both gametogenesis and
      steroidogenesis in human fetal testis. Our organ culture is an interesting tool
      for studying the effects of various factors on the development of human fetal
      testis, in particular the effect of hormone-disrupting chemicals.

PMID- 16621910
TI  - Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid
      disease: effects on obstetrical complications.
AB  - CONTEXT: Euthyroid women with autoimmune thyroid disease show impairment of
      thyroid function during gestation and seem to suffer from a higher rate of
      obstetrical complications. OBJECTIVE: We sought to determine whether these women
      suffer from a higher rate of obstetrical complications and whether levothyroxine
      (LT(4)) treatment exerts beneficial effects. DESIGN: This was a prospective
      study. SETTING: The study was conducted in the Department of Obstetrics and
      Gynecology. PATIENTS: A total of 984 pregnant women were studied from November
      2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)).
      INTERVENTION: TPOAb(+) patients were divided into two groups: group A (n = 57)
      was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-)
      patients (group C) served as a normal population control group. MAIN OUTCOME
      MEASURES: Rates of obstetrical complications in treated and untreated groups were
      measured. RESULTS: At baseline, TPOAb(+) had higher TSH compared with TPOAb(-);
      TSH remained higher in group B compared with groups A and C throughout gestation.
      Free T(4) values were lower in group B than groups A and C after 30 wk and after
      parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%,
      respectively), which was lower than group B (13.8%) [P < 0.05; relative risk
      (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95%
      CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature
      deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI =
      1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7).
      CONCLUSIONS: Euthyroid pregnant women who are positive for TPOAb develop impaired
      thyroid function, which is associated with an increased risk of miscarriage and
      premature deliveries. Substitutive treatment with LT(4) is able to lower the
      chance of miscarriage and premature delivery.

PMID- 16621911
TI  - Acute effects of ghrelin on insulin secretion and glucose disposal rate in
      gastrectomized patients.
AB  - CONTEXT: Plasma ghrelin concentration is diminished in gastrectomized patients.
      Acute ghrelin administration reduces insulin secretion, whereas insulin infusion
      has been shown to decrease ghrelin levels. Whether ghrelin has any effect on
      glucose utilization in humans is unknown. OBJECTIVE: Our objective was to reveal
      the effect of ghrelin on insulin-mediated glucose disposal in gastrectomized
      patients. STUDY AND SETTING: We conducted a double-blind, randomized, placebo
      controlled, hospital-based study. PATIENTS: Seven men and three women who all had
      a previous total gastrectomy and truncal vagotomy entered and completed the
      study. INTERVENTION: Each individual received infusion of saline alone or saline
      with ghrelin (5.0 pmol/kg.min) during a 5-h hyperinsulinemic (80 mU/m(2).min)
      euglycemic clamp on 2 separate days. MAIN OUTCOME MEASURES: We assessed glucose
      disposal rate and concentrations of C-peptide, ghrelin, GH, IGF-I, IGF-binding
      protein (IGFBP)-3 and -1, cortisol, leptin, and adiponectin. RESULTS: Glucose
      disposal rate decreased during ghrelin infusion (control study 8.6 +/- 0.2 vs.
      7.2 +/- 0.1 mg/kg.min P < 0.001). In experiments with saline infusion, levels of
      ghrelin (P < 0.001), C-peptide (P < 0.001), glucagon (P < 0.001), adiponectin (P
      = 0.005), cortisol (P = 0.012), IGF-I (P < 0.001), IGFBP-3 (P = 0.038), and IGFBP
      1 (P = 0.001) fell in response to euglycemic hyperinsulinemia. GH concentration
      maintained at baseline, whereas leptin significantly rose (P < 0.001). In the
      ghrelin infusion study, the plateau level of ghrelin concentration (6963.6 +/-
      212.9 pg/ml) was maintained from 90 min throughout the experiment. GH (P < 0.001)
      and cortisol (P = 0.04) concentrations rose, whereas C-peptide levels were more
      suppressed than in the control study (P < 0.001). Other hormones and IGFBPs
      changed similarly as in the study with saline infusion. CONCLUSION: It appears
      that ghrelin might be involved in the negative control of insulin secretion and
      glucose consumption in gastrectomized patients, at least after acute
      administration.

PMID- 16621912
TI  - Estimating the zero-equivalent dose (ZED) .

PMID- 16621913
TI  - The rate of adaptive evolution in enteric bacteria.
AB  - Here we estimate the rate of adaptive substitution in a set of 410 genes that are
      present in 6 Escherichia coli and 6 Salmonella enterica genomes. We estimate that
      more than 50% of amino acid substitutions in this set of genes have been fixed by
      positive selection between the E. coli and S. enterica lineages. We also show
      that the proportion of adaptive substitutions is uncorrelated with the rate of
      amino acid substitution or gene function but that it may be correlated with
      levels of synonymous codon usage bias.

PMID- 16621914
TI  - Evidence that protein length expansion and contraction is partly due to
      mutational events in premeiotic cells.
AB  - Studies on the rate of evolution of proteins typically concentrate on rates of
      change of orthologous amino acids rather than on changes in size (i.e.,
      generation of nonorthologous domains). Recent work has focused attention on
      Ser/Thr-rich regions in yeast as these tend to undergo size changes rapidly, with
      size polymorphisms commonly being found, especially in proteins with cell-surface
      localization. The underlying mechanism generating the indels is presently unclear
      though, due to a lack of correlation with the location of meiotic double-strand
      breaks, it has, by exclusion, been conjectured to be replication slippage. Here
      we provide new evidence to support this possibility. Notably, we show that
      Ser/Thr-rich repeat regions are more generally associated with the location of
      Mre11p in premeiotic cells. This is to be expected if the repeats were produced
      by mutational events in mitotic cells possibly through replication slippage.

PMID- 16621915
TI  - The pharmacokinetics of an albumin-binding Fab (AB.Fab) can be modulated as a
      function of affinity for albumin.
AB  - An AB.Fab (albumin-binding Fab) consists of a Fab and a phage-derived albumin
      binding peptide. This molecule is capable of binding both antigen and albumin
      simultaneously. Using a Fab derived from Herceptin we generated a panel of AB.Fab
      variants with wide-ranging affinities for albumin. An assay that measured AB.Fab
      binding to albumin in solution was developed to most accurately reflect the
      binding affinity for albumin in vivo. Affinity varied depending upon the species
      of albumin tested. For rat and rabbit albumin, affinities ranged from 0.04 to 2.5
      microM. Reduced affinity for albumin correlated with a reduced half-life and
      higher clearance rates in both species; the beta half-life ranged 6-fold while
      clearance ranged over 50-fold in rats and 20-fold in rabbits. To estimate the
      pharmacokinetic properties of an AB.Fab in humans, AB.Fab variants with similar
      affinities for rat and rabbit albumin were selected. Using their pharmacokinetic
      parameters and the principles of allometric scaling for albumin, we estimate an
      approximate beta half-life for an AB.Fab with 0.5 microM affinity for albumin of
      up to 4 days in humans with a clearance of 76 ml/h. These variants demonstrate
      the ability to modulate the clearance of a Fab fragment in vivo and help to
      establish guidelines for pharmacokinetic engineering of molecules through albumin
      binding.

PMID- 16621916
TI  - Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223
      Japanese patients.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motoneuron disease
      caused by a CAG-repeat expansion in the androgen receptor (AR) gene and for which
      no curative therapy exists. However, since recent research may provide
      opportunities for medical treatment, information concerning the natural history
      of SBMA would be beneficial in planning future clinical trials. We investigated
      the natural course of SBMA as assessed by nine activities of daily living (ADL)
      milestones in 223 Japanese SBMA patients (mean age at data collection = 55.2
      years; range = 30-87 years) followed from 1 to 20 years. All the patients were
      diagnosed by genetic analysis. Hand tremor was an early event that was noticed at
      a median age of 33 years. Muscular weakness occurred predominantly in the lower
      limbs, and was noticed at a median age of 44 years, followed by the requirement
      of a handrail to ascend stairs at 49, dysarthria at 50, dysphagia at 54, use of a
      cane at 59 and a wheelchair at 61 years. Twenty-one of the patients developed
      pneumonia at a median age of 62 and 15 of them died at a median age of 65 years.
      The most common cause of death in these cases was pneumonia and respiratory
      failure. The ages at onset of each ADL milestone were strongly correlated with
      the length of CAG repeats in the AR gene. However CAG-repeat length did not
      correlate with the time intervals between each ADL milestone, suggesting that
      although the onset age of each ADL milestone depends on the CAG-repeat length in
      the AR gene, the rate of disease progression does not. The levels of serum
      testosterone, an important triggering factor for polyglutamine-mediated
      motoneuron degeneration, were maintained at relatively high levels even at
      advanced ages. These results provide beneficial information for future clinical
      therapeutic trials, although further detailed prospective studies are also
      needed.

PMID- 16621917
TI  - Phenotypic spectrum associated with mutations of the mitochondrial polymerase
      gamma gene.
AB  - Mutations in the gene coding for the catalytic subunit of the mitochondrial DNA
      (mtDNA) polymerase gamma (POLG1) have recently been described in patients with
      diverse clinical presentations, revealing a complex relationship between genotype
      and phenotype in patients and their families. POLG1 was sequenced in patients
      from different European diagnostic and research centres to define the phenotypic
      spectrum and advance understanding of the recurrence risks. Mutations were
      identified in 38 cases, with the majority being sporadic compound heterozygotes.
      Eighty-nine DNA sequence changes were identified, including 2 predicted to alter
      a splice site, 1 predicted to cause a premature stop codon and 13 predicted to
      cause novel amino acid substitutions. The majority of children had a mutation in
      the linker region, often 1399G-->A (A467T), and a mutation affecting the
      polymerase domain. Others had mutations throughout the gene, and 11 had 3 or more
      substitutions. The clinical presentation ranged from the neonatal period to late
      adult life, with an overlapping phenotypic spectrum from severe encephalopathy
      and liver failure to late-onset external ophthalmoplegia, ataxia, myopathy and
      isolated muscle pain or epilepsy. There was a strong gender bias in children,
      with evidence of an environmental interaction with sodium valproate. POLG1
      mutations cause an overlapping clinical spectrum of disease with both dominant
      and recessive modes of inheritance. 1399G-->A (A467T) is common in children, but
      complete POLG1 sequencing is required to identify multiple mutations that can
      have complex implications for genetic counselling.

PMID- 16621918
TI  - Central core disease is due to RYR1 mutations in more than 90% of patients.
AB  - Ryanodine receptor 1 (RYR1) gene mutations are associated with central core
      disease (CCD), multiminicore disease (MmD) and malignant hyperthermia (MH), and
      have been reported to be responsible for 47-67% of patients with CCD and rare
      cases with MmD. However, to date, the true frequency and distribution of the
      mutations along the RYR1 gene have not been determined yet, since mutation
      screening has been limited to three 'hot spots', with particular attention to the
      C-terminal region. In this study, 27 unrelated Japanese CCD patients were
      included. Clinical histories and muscle biopsies were carefully reviewed. We
      sequenced all the 106 exons encoding RYR1 with their flanking exon-intron
      boundaries, and identified 20 novel and 3 previously reported heterozygous
      missense mutations in 25 of the 27 CCD patients (93%), which is a much higher
      mutation detection rate than that perceived previously. Among them, six were
      located outside the known 'hot spots'. Sixteen of 27 (59%) CCD patients had
      mutations in the C-terminal 'hot spot'. Three CCD patients had a probable
      autosomal recessive disease with two heterozygous mutations. Patients with C
      terminal mutations had earlier onset and rather consistent muscle pathology
      characterized by the presence of distinct cores in almost all type 1 fibres,
      interstitial fibrosis and type 2 fibre deficiency. In contrast, patients with
      mutations outside the C-terminal region had milder clinical phenotype and harbour
      more atypical cores in their muscle fibres. We also sequenced two genes encoding
      RYR1-associated proteins as candidate causative genes for CCD: the 12 kD FK506
      binding protein (FKBP12) and the alpha1 subunit of L-type voltage-dependent
      calcium channel or dihydropyridine receptor (CACNA1S). However, no mutation was
      found, suggesting that these genes may not, or only rarely, be responsible for
      CCD. Our results indicate that CCD may be caused by RYR1 mutations in the
      majority of patients.

PMID- 16621919
TI  - Internet gambling: an emerging concern in family practice medicine?
AB  - BACKGROUND: Gambling problems are rarely brought to the attention of family
      practice physicians, but pathological gambling can be associated with poor
      emotional and physical health. Recent availability and easy accessibility of
      Internet gambling may be associated with pathological gambling status, and
      Internet gambling may confer health risks. OBJECTIVE: This study evaluated the
      prevalence of Internet gambling, its association with pathological gambling, and
      the relationship between Internet gambling and health status among patients
      attending medical and dental clinics. METHODS: The South Oaks Gambling Screen and
      Short Form 12 were administered to 1414 adults in waiting areas of clinics.
      RESULTS: Only 6.9% of respondents reported ever gambling on the Internet, with
      2.8% indicating frequent Internet wagering. Almost two-thirds (65.9%) of regular
      Internet gamblers were classified as probable pathological gamblers, compared
      with 29.8% of ever-Internet gamblers and 7.6% of non-Internet gamblers. Internet
      gambling was associated with poor mental and physical health, and this
      association remained significant even after controlling for age, gender, site and
      pathological gambling status. CONCLUSIONS: These data suggest that Internet
      gambling is linked to pathological gambling and is independently associated with
      poor health. Family practice physicians should consider referring patients who
      gamble on the Internet for further treatment.

PMID- 16621920
TI  - Developments in rheumatology consultant manpower provision: the BSR/arc Workforce
      Register 2003-05.
AB  - OBJECTIVES: To summarize the changes and continuing inequalities in rheumatology
      service provision in the UK between 2001 and 2005. METHODS: Questionnaires about
      demographics and workload were sent to all consultants on the BSR/arc Workforce
      Register in January 2003 and 2005. RESULTS: A total of 94% of 506 consultants
      responded in 2003 and 89% of 542 in 2005. About 19% of the consultants practice
      rheumatology with acute medicine. Levels of optimal provision exceed 60% in
      England and Wales, but are below 50% in Scotland and Northern Ireland. The levels
      of provision in London are substantially higher than anywhere else. The median
      number of hours worked per week has increased from 35.2 in 2003 to 41 in 2005.
      CONCLUSIONS: Rheumatology continues to expand. There is inequality with better
      provision in England (especially London) and Wales than Scotland and Northern
      Ireland. Patterns of nurse and Senior House Officer (SHO) provision correlate
      with consultant numbers. Thus, the catalyst for improved service is consultant
      expansion.

PMID- 16621922
TI  - Overall fibromyalgia pain is predicted by ratings of local pain and pain-related
      negative affect--possible role of peripheral tissues.
AB  - OBJECTIVES: Despite variable numbers and intensities of local pain areas,
      fibromyalgia (FM) patients can provide overall clinical pain ratings. We
      hypothesized that the overall clinical pain is largely determined by the pain
      intensity of local body areas. Thus, we assessed the role of local body pains as
      predictors of overall clinical pain in FM patients. METHODS: Ratings of overall
      clinical pain intensity and pain-related negative affect (PRNA) were obtained
      from 277 FM patients. In addition, the patients identified painful body areas by
      shading a body pain diagram and rated the intensity of each pain area using a
      mechanical visual analogue scale (VAS). Hierarchical regression analyses were
      used to examine predictors of overall clinical FM pain intensity including PRNA,
      number of local pain areas, and maximal/average intensity of local pain areas.
      RESULTS: The average overall clinical pain rating of all FM patients was 4.6
      (S.D. 2.3) VAS. The PRNA accounted for 19%, number of painful body areas for 9%
      and maximal/average local pain for 27% of the variance of overall clinical FM
      pain (P-values < 0.001). The combination of all factors predicted 55% of the
      variance in overall clinical pain intensity of FM patients. CONCLUSION:
      Peripheral factors (maximal/average local pain and number of painful body areas)
      predicted most of the variance of overall clinical FM pain, suggesting that the
      input of pain by the peripheral tissues is clinically relevant. About 19% of the
      pain variance was predicted by PRNA. Thus, peripheral pain and negative affect
      appear to be particularly relevant for overall FM pain and may represent
      important targets for future therapies.

PMID- 16621921
TI  - Association between increased CCL2 (MCP-1) expression in lesions and persistence
      of disease activity in giant-cell arteritis.
AB  - OBJECTIVE: Patients with giant-cell arteritis (GCA) usually respond dramatically
      to corticosteroid treatment. However, recurrences are frequent and corticosteroid
      requirements are highly variable among patients. The aim of our study was to
      identify genes potentially involved in disease persistence. METHODS: Gene
      expression was explored with cDNA arrays in temporal artery biopsies from six GCA
      patients with relapsing disease and six patients who easily achieved sustained
      remission. Differentially expressed genes of interest were subsequently analysed
      by quantitative real-time polymerase chain reaction (PCR) and
      immunohistochemistry in temporal artery biopsies from 35 patients with biopsy
      proven GCA and nine controls. RESULTS: CCL2 (MCP-1) was up-regulated in temporal
      artery samples from relapsing individuals. In the extended series of patients,
      CCL2 mRNA concentration in lesions was significantly higher than in controls (31
      +/- 15.6 vs 0.44 +/- 0.10, P = 0.0001). In addition, CCL2 was more abundant in
      patients who experienced two or more relapses during the first year compared with
      those who endured sustained remission (127 +/- 82 vs 11 +/- 5.5, P = 0.0233) and
      correlated with the cumulated prednisolone dose (R = 0.533, P = 0.0024). CCL2
      mRNA concentration correlated with IL-1beta (R = 0.45, P = 0.02), tumour necrosis
      factor-alpha (TNF-alpha) (R = 0.47, P = 0.013) and IL-6 (R = 0.52, P = 0.0053)
      mRNA. However, circulating CCL2 determined by ELISA was decreased in patients
      with strong systemic inflammatory response, suggesting that reduction in
      circulating CCL2 may reinforce the local gradient in lesions. CONCLUSION:
      Increased CCL2 (MCP-1) expression in lesions is associated with persistence of
      disease activity in GCA.

PMID- 16621924
TI  - The use of a cannabis-based medicine (Sativex) in the treatment of pain caused by
      rheumatoid arthritis.

PMID- 16621925
TI  - Genomewide gain-of-function genetic screen identifies functionally active genes
      in mouse embryonic stem cells.
AB  - Embryonic stem (ES) cells hold great promise for the future of medicine. To
      elucidate the molecular mechanisms that control ES cell self-renewal and
      differentiation, a comprehensive knowledge of the molecules involved in these
      processes is required. Here we describe an effective approach for genomewide
      identification of functionally active genes in ES cells. This approach combines
      genetic screens based on cDNA libraries with microarray detection methods to
      permit high-throughput functional analyses. We implement this strategy to
      identify genes whose overexpression can maintain phenotypic properties of
      undifferentiated mouse ES cells under differentiation-inducing conditions,
      specifically in the absence of leukemia inhibitory factor. The identified genes
      encode a variety of regulatory proteins whose function in ES cells was previously
      unknown. Moreover, our approach is capable of detecting genes whose
      overexpression promote differentiation or cell death. Overall, our studies
      establish a methodology for highly sensitive identification of genes that confer
      particular phenotypes on ES cells.

PMID- 16621927
TI  - Electronic personal health records come of age.

PMID- 16621928
TI  - Possible involvement of crosstalk cell-adhesion mechanism by endometrial
      CD26/dipeptidyl peptidase IV and embryonal fibronectin in human blastocyst
      implantation.
AB  - When human blastocysts hatch through the zona pellucida, gaining the ability to
      adhere to the endometrium, crosstalk between the embryo and the uterus may
      represent a successful outcome of their synchronized development and
      differentiation. CD26/dipeptidyl peptidase IV is known as a marker molecule of
      the implantation phase endometrium. To study the role of CD26 in implantation, 35
      human hatched blastocysts were prepared by enzymatic treatment of expanded
      blastocysts that had been grown on schedule from frozen-thawed surplus embryos at
      the 2- or 4-cell stage. The blastocysts were placed on CD26-overexpressing or
      mock-transfected control monolayer cell cultures. The CD26-overexpression caused
      significantly higher blastocyst adhesion rate (53.3% versus 25.0%, P < 0.05) and
      significantly larger outgrowth area of trophectoderm (1.7-fold, P < 0.05). The
      second part of the present study was to show the expression of fibronectin, a
      CD26 ligand, in human preimplantation embryos, using the same donated resources.
      Fibronectin mRNA was detected by RT-PCR from the single hatched blastocyst (2/2)
      and from the single early blastocyst (3/6) but not from the single morula (0/5)
      samples. An indirect immunofluorescence technique verified the localization of
      fibronectin on the surface of the blastocyst. These results indicate that the
      adhesion mechanism by endometrial CD26 and embryonal fibronectin may be involved
      in human blastocyst implantation.

PMID- 16621929
TI  - Correlation between hepatic tumor blood flow and glucose utilization in a rabbit
      liver tumor model.
AB  - PURPOSE: To prospectively determine the relationship between hepatic tumor blood
      flow and glucose utilization in vivo by using a combined positron emission
      tomographic (PET)/computed tomographic (CT) scanner. MATERIALS AND METHODS: The
      animal care and use subcommittee at the University of Western Ontario approved
      this study. VX2 carcinoma cells were implanted in the livers of eight male New
      Zealand white rabbits. Functional CT was performed before tumor implantation and
      every 4 days thereafter. Each examination consisted of two phases: In the first
      phase, 30-second cine breath-hold scanning was performed with simultaneous
      injection of 5 mL of contrast material. In the second phase, 4-second cine
      scanning was performed without breath holding every 10 seconds for 2 minutes.
      Second-phase CT images were coregistered with first-phase images to eliminate
      breathing artifacts. The weighted summation of the aortic and portal venous time
      attenuation curves was deconvolved against curves from the liver to derive
      hepatic blood flow (HBF). Five animals underwent fluorine 18 fluorodeoxyglucose
      (FDG) scanning before and every 8 days after implantation. FDG uptake was
      measured as standardized uptake value (SUV). Data were analyzed with repeated
      measures analysis of variance and the Tukey-Kramer multiple comparison test.
      Linear regression was used to compare SUV and HBF in tumors and normal tissue.
      RESULTS: In the hypovascular tumor core, (a) mean HBF decreased from 262 mL.min
      1.100 g-1+/-22 (standard deviation) at baseline to 101 mL.min-1.100 g-1+/-62 at
      the end of the study (P<.05) and (b) mean SUV increased from 2.12 g/mL+/-0.06 to
      4.56 g/mL+/-0.73 (P<.05) during the same period. CONCLUSION: Functional CT in
      combination with FDG PET can be used to observe changes in HBF and glucose
      utilization in a growing liver tumor.

PMID- 16621930
TI  - Esophageal cancer: evaluation with triple-phase dynamic CT--initial experience.
AB  - PURPOSE: To prospectively assess which phase of a triple-phase dynamic contrast
      material-enhanced multi-detector row computed tomography (CT) protocol is optimal
      for visualization of esophageal cancer. MATERIALS AND METHODS: The study was
      supported by the local ethical committee; all patients gave written informed
      consent. Thirty-one lesions in 28 consecutive patients (26 men, two women; mean
      age, 65 years; range, 53-87 years) with histopathologically confirmed esophageal
      cancer were evaluated with triple-phase dynamic CT performed at 5, 35, and 65
      seconds (first arterial, second arterial, and venous phases) after attenuation of
      200 HU was obtained at the descending aorta. Qualitative image analysis was
      performed to assess appearance and conspicuity of the tumor. Appearances of all
      31 lesions were classified into three categories-not identifiable, focal
      enhancement with or without minimal (<1 cm) wall thickening, and focal mass
      lesion or obvious (>1 cm) wall thickening. Results were compared with surgical or
      endoscopic ultrasonographic findings. Quantitative assessment included regions-of
      interest measurement of the tumor and normal esophageal wall and the difference
      between those measurements. A paired t test was used to determine which phase
      showed the highest tumor attenuation and tumor-to-normal esophageal wall
      attenuation differences. RESULTS: At visual assessment, 30 lesions were
      identified in the second arterial phase. Of these 30 lesions, eight were focal
      enhancements; the best conspicuity was during the second arterial phase.
      Furthermore, seven of these eight lesions were T1 cancers. The remaining 22
      lesions were enhanced masses or wall thickening. Twenty-one of these 22 tumors
      also showed best conspicuity in the second arterial phase. The greatest
      attenuation of tumors in the second arterial phase was 130.0 HU, and the
      difference in attenuation between tumor and normal esophageal wall was 50.6 HU in
      the second arterial phase, which were significantly higher than those in the
      other two phases (P<.01, each). CONCLUSION: The second arterial phase of dynamic
      CT is the optimal phase for visualization of esophageal cancer.

PMID- 16621931
TI  - Multiple-image in-room CT imaging guidance for interventional procedures.
AB  - This HIPAA-compliant study was approved by the institutional review board;
      informed consent was not required. The purpose of this study was to
      retrospectively compare room use time for interventional procedures performed
      with multiple-image multi-detector row computed tomographic (CT) fluoroscopy
      (n=196) and single-image spiral CT fluoroscopy (n=175). There was no
      statistically significant difference in age, sex, or procedural type between the
      two groups. The median room use time was 90 minutes (interquartile range, 65-120
      minutes) for the single-image technique and 75 minutes (interquartile range, 60
      105 minutes) for the multiple-image technique. A two-sample t test with equal
      variance assumption on the log-transformed data showed a statistically
      significant difference in log time (P<.001) between the two groups. This time
      savings could potentially have a substantial clinical effect on resource use and
      patient throughput.

PMID- 16621932
TI  - The role of the polymorphic efflux transporter P-glycoprotein on the brain
      accumulation of d-methylphenidate and d-amphetamine.
AB  - The psychostimulant medications methylphenidate (MPH) and amphetamine (AMP),
      available in various ratios or enantiopure formulations of their respective
      active dextrorotary isomers, constitute the majority of agents used in the
      treatment of attention-deficit/hyperactivity disorder (ADHD). Substantial
      interindividual variability occurs in their pharmacokinetics and tolerability.
      Little is known regarding the potential role of drug transporters such as P
      glycoprotein (P-gp) in psychostimulant pharmacokinetics and response. Therefore,
      experiments were carried out in P-gp knockout (KO) mice versus wild-type (WT)
      mice after intraperitoneal dosing (2.5 mg/kg) of d-MPH or (3.0 mg/kg) of d-AMP.
      After the administration of each psychostimulant, locomotor activity was assessed
      at 30-min intervals for 2 h. Total brain-to-plasma drug concentration ratios were
      determined at 10-, 30-, and 80-min postdosing time-points. The results showed no
      statistically supported genotypic difference in d-AMP-induced locomotor activity
      stimulation or in brain-to-plasma ratio of d-AMP. As for d-MPH, the P-gp KO mice
      had 33% higher brain concentrations (p < 0.05) and 67.5% higher brain-to-plasma
      ratios (p < 0.01) than WT controls at the 10-min postdosing timepoint. However,
      in spite of elevated brain concentrations, d-MPH-induced locomotor activity
      increase was attenuated for P-gp compared with that for WT mice. These data
      indicate that P-gp has no apparent effect on the pharmacokinetics and
      pharmacodynamics of d-AMP. In addition, d-MPH is a relatively weak P-gp
      substrate, and its entry into the brain may be limited by P-gp. Furthermore, the
      mechanism by which d-MPH-induced locomotor activity was attenuated in P-gp KO
      mice remains to be elucidated.

PMID- 16621933
TI  - Selective effects of nitric oxide on the disposition of chlorzoxazone and
      dextromethorphan in isolated perfused rat livers.
AB  - The rapid and direct effects of nitric oxide (NO) donors sodium nitroprusside
      (SNP) and isosorbide dinitrate (ISDN) on the hepatic and biliary disposition of
      chlorzoxazone (CZX), a marker of CYP2E1, and dextromethorphan (DEM), a marker of
      CYP2D1, were studied in a single-pass isolated perfused rat liver model. Livers
      (n = 30) were perfused with constant concentrations of NO donors (0-120 min) in
      addition to infusion of CZX or DEM (60-120 min), and periodical outlet and bile
      samples were collected. Both ISDN and SNP significantly reduced (30 and 60%,
      respectively) the hepatic extraction ratio of CZX and decreased (50 and 70%,
      respectively) the recovery of the CYP2E1-mediated metabolite, 6
      hydroxychlorzoxazone, in the outlet perfusate and bile. As for DEM, both NO
      donors increased (up to 3.5-fold) the recovery of the CYP2D1-mediated metabolite
      dextrorphan (DOR) in the outlet perfusate. However, this was associated with a
      simultaneous decrease (50-75%) in the excretion of the metabolite into the bile,
      thus resulting in no change in the overall recovery of DOR as a result of NO
      donor treatment. The decrease in the biliary excretion of DOR was caused by NO
      induced simultaneous reductions in both the conjugation of DOR and biliary
      clearance of DOR conjugate. Additionally, both SNP and ISDN significantly reduced
      the metabolism of DEM to 3-hydroxymorphinan, which is mostly regulated by CYP3A2.
      These studies in an intact liver model confirm the selectivity of the inhibitory
      effects of NO donors on cytochrome P450 enzymes, which was recently reported in
      microsomal studies, and expand these inhibitory effects to conjugation pathways.

PMID- 16621934
TI  - First-pass effects of verapamil on the intestinal absorption and liver
      disposition of fexofenadine in the porcine model.
AB  - The aim of this study in pigs was to investigate the local pharmacokinetics of
      fexofenadine in the intestine and liver by using the pig as a model for drug
      transport in the entero-hepatobiliary system. A parallel group design included
      seven pigs (10-12 weeks, 22.2-29.5 kg) in three groups (G1, G2, G3), and a
      jejunal single-pass perfusion combined with sampling from the bile duct and the
      portal, hepatic, and superior caval veins was performed. Fexofenadine was
      perfused through the jejunal segment alone (G1: 120 mg/l, total dose 24 mg) or
      with two different verapamil doses (G2: 175 mg/l, total dose 35 mg; and G3: 1000
      mg/l, total dose 200 mg). The animals were fully anesthetized and monitored
      throughout the experiment. Fexofenadine had a low liver extraction (E(H); mean +/
      S.E.M.), and the given doses of verapamil did not affect the E(H) (0.13 +/-
      0.04, 0.16 +/- 0.03, and 0.12 +/- 0.02 for G1, G2, and G3, respectively) or
      biliary clearance. The E(H) for verapamil and antipyrine agreed well with human
      in vivo data. Verapamil did not increase the intestinal absorption of
      fexofenadine, even though the jejunal permeability of fexofenadine, verapamil,
      and antipyrine showed a tendency to increase in G2. This combined perfusion and
      hepatobiliary sampling method showed that verapamil did not affect the transport
      of fexofenadine in the intestine or liver. In this model the E(H) values for both
      verapamil and antipyrine were similar to the corresponding values in vivo in
      humans.

PMID- 16621935
TI  - Induction of genes for metabolism and transport by trans-stilbene oxide in livers
      of Sprague-Dawley and Wistar-Kyoto rats.
AB  - trans-Stilbene oxide (TSO) is a synthetic proestrogen that induces phase I and II
      drug-metabolizing enzymes in rat liver. The purpose of this study was to
      determine whether TSO also induces transporter expression in rat liver and
      whether gene induction in rat liver after TSO occurs in a constitutive androstane
      receptor (CAR)-dependent manner. Total RNA was isolated from male rat livers
      after treatment with TSO for up to 4 days (200 mg/kg, i.p., twice daily), and the
      mRNA levels for each gene were quantified. CYP2B1/2, CYP3A1, epoxide hydrolase,
      heme oxygenase-1, UGT1A6, UGT2B1, multiple drug resistance protein (Mdr) 1a and
      1b, as well as multidrug resistance-associated protein (Mrp) 2, 3, and 4 mRNA
      were increased in livers after TSO treatment. To determine whether TSO activates
      gene expression in a CAR-dependent manner, male and female Wistar-Kyoto (WKY)
      rats were treated with TSO for 3 days. TSO induced CYP2B1/2, UGT2B1, and Mdr1b in
      males more than in females, suggesting that TSO could increase their expression
      via CAR. Conversely, TSO induced CYP3A1, epoxide hydrolase, UGT1A6, and Mrp3
      similarly in both genders, indicating that induction of these genes occurs
      independently of CAR. TSO treatment also increased the activity of a CAR binding
      element luciferase reporter construct in HepG2 cells transfected with rat CAR and
      in mouse liver. Additionally, TSO increased antioxidant response
      element/electrophile response element luciferase reporter construct activity in
      HepG2 cells. In conclusion, in WKY rat liver, TSO increases CYP2B1/2, UGT2B1, and
      Mdr1b mRNA expression in a gender-dependent manner and CYP3A1, epoxide hydrolase,
      UGT1A6, and Mrp3 in a gender-independent manner.

PMID- 16621936
TI  - Extrapolation of preclinical pharmacokinetics and molecular feature analysis of
      "discovery-like" molecules to predict human pharmacokinetics.
AB  - The prediction of human pharmacokinetics from preclinical species is an integral
      component of drug discovery. Recent studies with a 103-compound dataset suggested
      that scaling from monkey pharmacokinetic data tended to be the most accurate
      method for predicting human clearance. Additionally, interrogation of the two
      dimensional molecular properties of these molecules produced a set of
      associations which predict the likely extrapolative outcome (success or failure)
      of preclinical data to project human pharmacokinetics. However, a limitation of
      the previous analyses was the relative paucity of data for typical "discovery
      like" molecules (molecular weight >300 and/or clogP >3). The objective of this
      investigation was to generate preclinical data required for extension of this
      dataset for additional discovery-like molecules and determine whether the
      aforementioned findings continue to apply for these molecules. In vivo nonrodent
      intravenous pharmacokinetic data were generated for 13 molecules, and data for 8
      additional molecules were obtained from the literature. Additionally, the various
      scaling methodologies and molecular features analysis were applied to this new
      dataset to predict human pharmacokinetics. Whereas the predictive accuracies
      demonstrated across all of the various methodologies were lower for this higher
      clearance compound dataset, scaling from monkey liver blood flow continued to be
      an accurate methodology, and human volume of distribution was similarly well
      predicted regardless of scaling methodology. Lastly, application of the molecular
      feature associations, particularly data-dependent associations, afforded an
      improved predictivity compared with the liver blood flow scaling approaches, and
      provides insight into the extrapolation of high clearance compounds in the
      preclinical species to human.

PMID- 16621938
TI  - Constraints of tolerance: why are desiccation-tolerant organisms so small or
      rare?
AB  - Drying to equilibrium with the air kills nearly all animals and flowering plants,
      including livestock and crops. This makes drought a key ecological problem for
      terrestrial life and a major cause of human famine. However, the ability to
      tolerate complete desiccation is widespread in organisms that are either <5 mm
      long or found mainly where desiccation-sensitive organisms are scarce. This
      suggests that there is a trade-off between desiccation tolerance and growth.
      Recent molecular and biochemical research shows that organisms tolerate
      desiccation through a set of mechanisms, including sugars that replace water and
      form glasses, proteins that stabilize macromolecules and membranes, and anti
      oxidants that counter damage by reactive oxygen species. These protections are
      often induced by drying, and some of the genes involved may be homologous in
      microbes, plants and animals. Understanding how mechanisms of desiccation
      tolerance may constrain growth might show how to undo the constraint in some
      economically important macroorganisms and elucidate the much-studied but elusive
      relationship between tolerance of stress and productivity.

PMID- 16621939
TI  - The role of mechanosensory input in flower handling efficiency and learning by
      Manduca sexta.
AB  - Nectar-foraging animals are known to utilize nectar guides-- patterns of visual
      contrast in flowers-- to find hidden nectar. However, few studies have explored
      the potential for mechanosensory cues to function as nectar guides, particularly
      for nocturnal pollinators such as the tobacco hornworm moth, Manduca sexta. We
      used arrays of artificial flowers to investigate the flower handling behavior
      (the ability to locate and drink from floral nectaries) of naive moths, looking
      specifically at: (1) how the shape and size of flat (two-dimensional) artificial
      corollas affect nectar discovery and (2) whether three-dimensional features of
      the corolla can be used to facilitate nectar discovery. In these experiments, we
      decoupled visual from tactile flower features to explore the role of
      mechanosensory input, putatively attained via the extended proboscides of
      hovering moths. In addition, we examined changes in nectar discovery times within
      single foraging bouts to test whether moths can learn to handle different kinds
      of artificial flowers. We found that corolla surface area negatively affects
      flower handling efficiency, and that reliable mechanosensory input is crucial for
      the moths' performance. We also found that three-dimensional features of the
      corolla, such as grooves, can significantly affect the foraging behavior, both
      positively (when grooves converge to the nectary) and negatively (when grooves
      are unnaturally oriented). Lastly, we observed that moths can decrease nectar
      discovery time during a single foraging bout. This apparent learning ability
      seems to be possible only when reliable mechanosensory input is available.

PMID- 16621940
TI  - Tensilin-like stiffening protein from Holothuria leucospilota does not induce the
      stiffest state of catch connective tissue.
AB  - The dermis of sea cucumbers is a catch connective tissue or mutable connective
      tissue that exhibits large changes in mechanical properties. A stiffening
      protein, tensilin, has been isolated from the sea cucumber Cucumaria frondosa. We
      purified a similar protein, H-tensilin, from Holothuria leucospilota, which
      belongs to a different family to C. frondosa. H-tensilin appeared as a single
      band with an apparent molecular mass of 34 kDa on SDS-PAGE. No sugar chain was
      detected. Tryptic fragments of the protein had homology to known tensilin. H
      tensilin aggregated isolated collagen fibrils in vitro in a buffer containing 0.5
      mol l(-1) NaCl with or without 10 mmol l(-1) Ca(2+). The activity of H-tensilin
      was quantitatively studied by dynamic mechanical tests on the isolated dermis. H
      tensilin increased stiffness of the dermis in the soft state, induced by Ca(2+)
      free artificial seawater, to a level comparable to that of the standard state,
      which was the state found in the dermis rested in artificial seawater with normal
      ionic condition. H-tensilin decreased the energy dissipation ratio of the soft
      dermis to a level comparable to that of the standard state. When H-tensilin was
      applied on the dermis in the standard state, it did not alter stiffness nor
      dissipation ratio. The subsequent application of artificial seawater in which the
      potassium concentration was raised to 100 mmol l(-1) increased stiffness by one
      order of magnitude. These findings suggest that H-tensilin is involved in the
      changes from the soft state to the standard state and that some stiffening
      factors other than tensilin are necessary for the changes from the standard to
      the stiff state.

PMID- 16621941
TI  - Evidence from mosquitoes suggests that cyclic gas exchange and discontinuous gas
      exchange are two manifestations of a single respiratory pattern.
AB  - In this paper we demonstrate that the apparent pattern of gas exchange in
      insects, as observed using flow-through respirometry, is strongly affected by the
      rate of flow of air through the system. This is true not only because of the time
      constant of the respiratory chamber in which the insect resides, but also due to
      the effect of flow rate on the residence time of air as it passes through the
      detection chamber in the gas analyzer. It is demonstrated that insects respiring
      with a discontinuous gas exchange pattern can appear to be using a cyclic
      respiratory pattern. The effects of flow rate on the respiratory pattern
      discerned are illustrated using the mosquito Culiseta inornata. It is
      demonstrated that these mosquitoes respire discontinuously. They are among the
      smallest insects to date in which the discontinuous gas exchange cycle has been
      observed.

PMID- 16621942
TI  - Polarization sensitivity in the red swamp crayfish Procambarus clarkii enhances
      the detection of moving transparent objects.
AB  - We tested the hypothesis that polarization sensitivity enhances the detection of
      moving, transparent objects by examining the escape response of the red swamp
      crayfish (Procambarus clarkii Girard) from a visual threat. A transparent,
      birefringent target trans-illuminated by either partially linear polarized or
      unpolarized light was advanced toward individual crayfish. The optical axis of
      the target was aligned such that it would be conspicuous to a viewer with
      polarization sensitivity when trans-illuminated by polarized light. Under
      polarized light, significantly more crayfish retreated from the target than under
      unpolarized light of identical intensity (P<0.00005, Fisher's exact test).
      Whereas the potential for polarization sensitivity has been shown in
      neurophysiological and structural studies of the visual system of P. clarkii and
      the signal crayfish Pasifastacus leniusculus (Dana), our results provide the
      first behavioral evidence for polarization sensitivity among crayfish. The
      ecological function of this ability is unclear, but it may enhance the detection
      of fish with silvered scales, transparent zooplankton or macroinvertebrates.
      Because escape responses are generally more reliably induced than other
      behaviors, the method employed in this study may prove useful for examining
      sensory capabilities in other species.

PMID- 16621943
TI  - Task-level control of rapid wall following in the American cockroach.
AB  - The American cockroach, Periplaneta americana, is reported to follow walls at a
      rate of up to 25 turns s(-1). During high-speed wall following, a cockroach holds
      its antenna relatively still at the base while the flagellum bends in response to
      upcoming protrusions. We present a simple mechanosensory model for the task-level
      dynamics of wall following. In the model a torsional, mass-damper system
      describes the cockroach's turning dynamics, and a simplified antenna measures
      distance from the cockroach's centerline to a wall. The model predicts that
      stabilizing neural feedback requires both proportional feedback (difference
      between the actual and desired distance to wall) and derivative feedback
      (velocity of wall convergence) information from the antenna. To test this
      prediction, we fit a closed-loop proportional-derivative control model to trials
      in which blinded cockroaches encountered an angled wall (30 degrees or 45 degrees
      ) while running. We used the average state of the cockroach in each of its first
      four strides after first contacting the angled wall to predict the state in each
      subsequent stride. Nonlinear statistical regression provided best-fit model
      parameters. We rejected the hypothesis that proportional feedback alone was
      sufficient. A derivative (velocity) feedback term in the control model was
      necessary for stability.

PMID- 16621944
TI  - Parathyroid hormone may maintain bone formation in hibernating black bears (Ursus
      americanus) to prevent disuse osteoporosis.
AB  - Mechanical unloading of bone causes an imbalance in bone formation and resorption
      leading to bone loss and increased fracture risk. Black bears (Ursus americanus)
      are inactive for up to six months during hibernation, yet bone mineral content
      and strength do not decrease with disuse or aging. To test whether hibernating
      bears have biological mechanisms to prevent disuse osteoporosis, we measured the
      serum concentrations of hormones and growth factors involved in bone metabolism
      and correlated them with the serum concentration of a bone formation marker
      (osteocalcin). Serum was obtained from black bears over a 7-month duration that
      included periods of activity and inactivity. Both resorption and formation
      markers increased during hibernation, suggesting high bone turnover occurred
      during inactivity. However, bone formation appeared to be balanced with bone
      resorption. The serum concentration of parathyroid hormone (PTH) was higher in
      the hibernation (P=0.35) and post-hibernation (P=0.006) seasons relative to pre
      hibernation levels. Serum leptin was lower (P<0.004) post-hibernation relative to
      pre-hibernation and hibernation periods. Insulin-like growth factor I (IGF-I)
      decreased (P<0.0001) during hibernation relative to pre-hibernation and reached
      its highest value during remobilization. There was no difference (P=0.64) in 25
      OH vitamin D between the three seasons. Serum osteocalcin (bone formation marker)
      was significantly correlated with PTH, but not with leptin, IGF-I or 25-OH
      vitamin D. Osteocalcin and PTH were positively correlated when samples from all
      seasons were pooled and when only hibernation samples were considered, raising
      the possibility that the anabolic actions of PTH help maintain bone formation to
      prevent disuse osteoporosis. Prostaglandin E(2) (PGE(2)) release from MC3T3
      osteoblastic cells was significantly affected by treatment with bear serum from
      different seasons (i.e. hibernation versus active periods). The seasonal changes
      in PGE(2) release showed trends similar to the seasonal changes in serum IGF-I.
      Since both PGE(2) and IGF-I are associated with collagenous bone formation, it is
      possible that seasonal changes in a circulating factor influence IGF-I levels in
      vivo in bears and PGE(2) release in osteoblastic cells in vitro. The significant
      decrease in serum leptin following arousal from hibernation may promote bone
      formation during remobilization, assuming there is a similar decrease in
      intracerebroventricular leptin. These findings support the idea that seasonal
      changes in the concentration of circulating molecules help regulate bone
      formation activity and may be important for preventing disuse osteoporosis in
      bears.

PMID- 16621945
TI  - Metabolic, respiratory and cardiovascular responses to acute and chronic hypoxic
      exposure in tadpole shrimp Triops longicaudatus.
AB  - Hypoxic exposure experienced during sensitive developmental periods can shape
      adult physiological capabilities and define regulatory limits. Tadpole shrimp
      were reared under normoxic (19-21 kPa O(2)), moderate (10-13 kPa O(2)) or severe
      (1-3 kPa O(2)) hypoxic conditions to investigate the influence of developmental
      oxygen partial pressure (P(O(2))) on adult metabolic, respiratory and
      cardiovascular physiology. Developmental P(O(2)) had no effect on metabolic rate
      or metabolic response to hypoxic exposure in adults. All rearing groups decreased
      O(2) consumption as water P(O(2)) decreased. Heart rate, stroke volume and
      cardiac output were independent of P(O(2)) down to 5 kPa O(2) in all rearing
      groups. Below this, cardiac output was maintained only in tadpole shrimp reared
      under severe hypoxic conditions. The enhanced ability to maintain cardiac output
      was attributed to an increase in hemoglobin concentration and O(2)-binding
      affinity in those animals. Oxygen-delivery potential was also significantly
      higher in the group reared under severe hypoxic conditions (1,336 microl O(2)
      min(-1)) when compared with the group reared under normoxic conditions (274
      microl O(2) min(-1)). Differences among the rearing groups that were dependent on
      hemoglobin were not considered developmental effects because hemoglobin
      concentration could be increased within seven days of hypoxic exposure
      independent of developmental P(O(2)). Hypoxia-induced hemoglobin synthesis may be
      a compensatory mechanism that allows tadpole shrimp to regulate O(2) uptake and
      transport in euryoxic (O(2) variable) environments. The results of this study
      indicate that increased hemoglobin concentration, increased O(2)-binding affinity
      and transient decreases in metabolic demand may account for tadpole shrimp
      hypoxic tolerance.

PMID- 16621946
TI  - Metabolic scaling associated with unusual size changes during larval development
      of the frog, Pseudis paradoxus.
AB  - The early larvae of P. paradoxus grow large but metamorphose into relatively
      small frogs, the diminished post-metamorphic growth producing a marked contrast
      between maximum larval size and adult. Thus, O(2) uptake does not appear to limit
      the energy expenditure on growth processes, and unlike in other anuran larvae,
      may not be a surface area-related function in P. paradoxus larvae. The resting
      rates of metabolism (M(O(2))) and partitioning between aquatic (Mw(O(2))) and
      aerial O(2) uptake (Ma(O(2))) were measured on tadpoles and froglets by closed
      system respirometry, using water of P(O(2)) ranging from 145 to 40 mmHg.
      Correlative changes in body glycogen and lactate were examined by standard enzyme
      assays. Scaling patterns in the growth and degrowth stages were analysed on whole
      body, log-transformed data using linear regressions. In normoxia, M(O(2)) was 2.1
      2.5 mumol g(-1) h(-1) in the early larvae, increasing more than twofold on
      forelimb emergence and decreasing sharply in the froglets; M(O(2)) varies in
      strict proportion to body mass (M(b)), both in the growth (b=1.02) and degrowth
      (b=0.97) phases, according to the equation M(O(2))=aM(b)(b), where b is the
      scaling coefficient. Mw(O(2)) constitutes >90% of total uptake in the growth
      stages, increasing with b=1.02 while Ma(O(2)) increases with b=1.13; during
      degrowth there is a change in the pattern related to intensification of
      metamorphosis. Hypoxic water did not affect M(O(2)); however, in all larval
      stages Mw(O(2)) and Ma(O(2)) changed with a decrease in P(O(2)). At 60 mmHg,
      rates are more severely affected in the largest tadpoles, causing the b values
      for Mw(O(2)) and Ma(O(2)) to change to 0.11 and 1.44, respectively, in the growth
      phase. Glycogen and lactate levels increase out of proportion with body mass
      increase (b=2.05 and 1.47, respectively) in the growth stages, and increase
      anaerobic capacity in late metamorphosis. In hypoxic water, glycogen levels
      decrease in the growth stages and the largest tadpoles accumulate surplus
      lactate, possibly related to surfacing activity. Our results may reveal the
      consequences of size on energy demand at the tissue level in P. paradoxus larvae,
      indicating that air breathing must subsidise energy expenditure during larval
      development.

PMID- 16621947
TI  - The significance of spiracle conductance and spatial arrangement for flight
      muscle function and aerodynamic performance in flying Drosophila.
AB  - During elevated locomotor activity such as flight, Drosophila satisfies its
      increased respiratory demands by increasing the total spiracle opening area of
      the tracheal gas exchange system. It has been assumed that in a diffusion-based
      system, each spiracle contributes to oxygen flux into and carbon dioxide flux out
      of the tracheal system according to the size of its opening. We evaluated this
      hypothesis by determining how a reduction in size and interference with the
      spatial distribution of gas exchange areas impair flight muscle function and
      aerodynamic force production in the small fruit fly Drosophila melanogaster. This
      was done by selectively blocking thoracic spiracles of tethered flies flying
      inside a flight simulator. Flow-through respirometry and simultaneous
      measurements of flight force production and wing kinematics revealed a negligible
      functional safety margin for respiration. Maximum locomotor performance was only
      achieved by unmanipulated flies, supporting the general assumption that at the
      animal's maximum locomotor capacity, maximum spiracle opening area matches
      respiratory need. The maximum total buffer capacity for carbon dioxide in
      Drosophila amounts to approximately 33.5 mul g(-1) body mass, estimated from the
      temporal integral of carbon dioxide release rate during the resting period after
      flight. By comparing flight variables in unmanipulated and 'spiracle-blocked'
      flies at comparable flight forces, we found that (i) stroke amplitude, stroke
      frequency and the chemo-mechanical conversion efficiency of the indirect flight
      musculature were broadly independent of the arrangement of spiracle conductance,
      while (ii) muscle mechanical power significantly increased, and (iii) mean lift
      coefficient and aerodynamic efficiency significantly decreased up to
      approximately 50% with an increasing number of blocked spiracles. The data
      suggest that Drosophila apparently maximizes the total efficiency of its
      locomotor system for flight by allowing oxygen delivery to the flight musculature
      through multiple spiracles of the thorax.

PMID- 16621948
TI  - Size, strength and allometry of joints in the articulated coralline Calliarthron.
AB  - Articulated coralline algae (Corallinales, Rhodophyta) dominate low-intertidal,
      wave-exposed habitats around the world, yet the mechanics of this diverse group
      of organisms has been almost completely unexplored. In contrast to fleshy
      seaweeds, articulated corallines consist of calcified segments (intergenicula)
      separated by uncalcified joints (genicula). This jointed construction makes
      calcified fronds as flexible as fleshy seaweeds, allowing them to ;go with the
      flow' when struck by breaking waves. In addition to functioning as joints,
      genicula act as breakage points along articulated fronds. Here, I describe the
      allometric scaling of geniculum size, breaking force and tissue strength along
      articulated fronds in two species of Calliarthron. Genicular material is much
      stronger than tissue from fleshy macroalgae. Moreover, as fronds grow, genicula
      get bigger and their tissue strengthens, two processes that help them resist
      breakage. Within individual fronds, larger branches, which presumably experience
      greater drag force, are supported by bigger, stronger genicula. However, frond
      growth greatly outpaces genicular strengthening. As a result, Calliarthron fronds
      most likely break at their bases when critically stressed by incoming waves.
      Shedding fronds probably reduces the drag force that threatens to dislodge
      coralline crusts and may constitute a reproductive strategy.

PMID- 16621949
TI  - Energy integration between the solitary polyps of the clonal coral Lobophyllia
      corymbosa.
AB  - Clonal integration in the coral Lobophyllia corymbosa was studied from two
      perspectives: transfer of carbon among clonemates and allorecognition. This coral
      forms colonies in the early post-metamorphic stages. In later ontogeny, the
      tissues interconnecting polyps die, transforming the colony into a clone of
      solitary polyps. These polyps continue to live in close proximity but without
      tissue continuity. Isolated polyps labeled with radioactive carbon in the light
      showed oriented transfer of assimilates towards adjacent, injured polyps. No
      significant transfer of carbon was observed towards intact, isogeneic polyps or
      allogeneic polyps. Grafting of coral tissues resulted in intra-clonal fusion, but
      only when polyps were previously sectioned. Allogeneic sectioned grafts were
      always rejected. Intact polyps were unresponsive towards isogeneic and allogeneic
      counterparts when grafted. Our results show that isolated Lobophyllia polyps not
      only recognize their clonemates as such, but also help them when necessary,
      although no tissue continuity exists between them.

PMID- 16621950
TI  - COX2 in a euryhaline teleost, Fundulus heteroclitus: primary sequence,
      distribution, localization, and potential function in gills during salinity
      acclimation.
AB  - In the kidneys of mammals, cyclooxygenase type 2 (COX2) is expressed in medullary
      interstitial cells, the macula densa and epithelial cells of the cortical thick
      ascending limb where it generates prostaglandins that regulate hormone secretion,
      inhibit ion transport, and support cell survival during salt loading and
      dehydration. In teleosts, the gills are in direct contact with an aquatic
      environment and are the dominant site of osmoregulation. During transfers between
      salinities, specialized cells in the gills (chloride cells) rapidly regulate NaCl
      secretion for systemic osmoregulation while they simultaneously are exposed to
      acute osmotic shock. This study was conducted to determine if COX2 is expressed
      in the gills, and if so, to evaluate its function in cellular and systemic
      osmoregulation. Degenerate primers, reverse transcription-PCR and rapid
      amplification of cDNA ends were used to deduce the complete cDNA sequence of a
      putative COX2 enzyme from the gills of the euryhaline killifish (Fundulus
      heteroclitus). The 2,738 base pair cDNA includes a coding region for a 610 amino
      acid protein that is over 70% identical to mammalian COX2. A purified antibody
      generated against a conserved region of mouse COX2 labeled chloride cells,
      suggesting that the enzyme may control NaCl secretion as an autocrine agent. Real
      time PCR was then used to demonstrate that mRNA expression of the COX2 homologue
      was threefold greater in gills from chronic seawater killifish than in gills from
      chronic freshwater killifish. Expression of Na(+)/K(+)/2Cl(-) cotransporter and
      the cystic fibrosis transmembrane conductance regulator were also greater in
      seawater, suggesting that chronic COX2 expression in the gills is regulated in
      parallel to the key ion transporters that mediate NaCl secretion. Real-time PCR
      was also used to demonstrate that acute transfer from seawater to freshwater and
      from freshwater to seawater led to rapid, transient inductions of COX2
      expression. Together with previous physiological evidence, the present molecular
      and immunological data suggest that constitutive branchial COX2 expression is
      enhanced in seawater, where prostaglandins can regulate NaCl secretion in
      chloride cells. Our data also suggest that branchial COX2 expression may play a
      role in cell survival during acute osmotic shock.

PMID- 16621951
TI  - The role of branchial and orobranchial O2 chemoreceptors in the control of
      aquatic surface respiration in the neotropical fish tambaqui (Colossoma
      macropomum): progressive responses to prolonged hypoxia.
AB  - The present study examined the role of branchial and orobranchial O(2)
      chemoreceptors in the cardiorespiratory responses, aquatic surface respiration
      (ASR), and the development of inferior lip swelling in tambaqui during prolonged
      (6 h) exposure to hypoxia. Intact fish (control) and three groups of denervated
      fish (bilateral denervation of cranial nerves IX+X (to the gills), of cranial
      nerves V+VII (to the orobranchial cavity) or of cranial nerves V alone), were
      exposed to severe hypoxia (Pw(O)2=10 mmHg) for 360 min. Respiratory frequency
      (fr) and heart rate (fh) were recorded simultaneously with ASR. Intact (control)
      fish increased fr, ventilation amplitude (V(AMP)) and developed hypoxic
      bradycardia in the first 60 min of hypoxia. The bradycardia, however, abated
      progressively and had returned to normoxic levels by the last hour of exposure to
      hypoxia. The changes in respiratory frequency and the hypoxic bradycardia were
      eliminated by denervation of cranial nerves IX and X but were not affected by
      denervation of cranial nerves V or V+VII. The V(AMP) was not abolished by the
      various denervation protocols. The fh in fish with denervation of cranial nerves
      V or V+VII, however, did not recover to control values as in intact fish. After
      360 min of exposure to hypoxia only the intact and IX+X denervated fish performed
      ASR. Denervation of cranial nerve V abolished the ASR behavior. However, all
      (control and denervated (IX+X, V and V+VII) fish developed inferior lip swelling.
      These results indicate that ASR is triggered by O(2) chemoreceptors innervated by
      cranial nerve V but that other mechanisms, such as a direct effect of hypoxia on
      the lip tissue, trigger lip swelling.

PMID- 16621952
TI  - Fluorescence measurements of serotonin-induced V-ATPase-dependent pH changes at
      the luminal surface in salivary glands of the blowfly Calliphora vicina.
AB  - Secretion in blowfly salivary glands is induced by the neurohormone serotonin and
      powered by a vacuolar-type H(+)-ATPase (V-ATPase) located in the apical membrane
      of the secretory cells. We have established a microfluorometric method for
      analysing pH changes at the luminal surface of the secretory epithelial cells by
      using the fluorescent dye 5-N-hexadecanoyl-aminofluorescein (HAF). After
      injection of HAF into the lumen of the tubular salivary gland, the fatty acyl
      chain of the dye molecule partitions into the outer leaflet of the plasma
      membrane and its pH-sensitive fluorescent moiety is exposed at the cell surface.
      Confocal imaging has confirmed that HAF distributes over the entire apical
      membrane of the secretory cells and remains restricted to this membrane domain.
      Ratiometric analysis of HAF fluorescence demonstrates that serotonin leads to a
      reversible dose-dependent acidification at the luminal surface. Inhibition by
      concanamycin A confirms that the serotonin-induced acidification at the luminal
      surface is due to H(+) transport across the apical membrane via V-ATPase.
      Measurements with pH-sensitive microelectrodes corroborate a serotonin-induced
      luminal acidification and demonstrate that luminal pH decreases by about 0.4 pH
      units at saturating serotonin concentrations. We conclude that ratiometric
      measurements of HAF fluorescence provide an elegant method for monitoring V
      ATPase-dependent H(+) transport in the blowfly salivary gland in vivo and for
      analysing the spatiotemporal pattern of pH changes at the luminal surface.

PMID- 16621953
TI  - Terrestrial locomotion of the New Zealand short-tailed bat Mystacina tuberculata
      and the common vampire bat Desmodus rotundus.
AB  - Bats (Chiroptera) are generally awkward crawlers, but the common vampire bat
      (Desmodus rotundus) and the New Zealand short-tailed bat (Mystacina tuberculata)
      have independently evolved the ability to manoeuvre well on the ground. In this
      study we describe the kinematics of locomotion in both species, and the kinetics
      of locomotion in M. tuberculata. We sought to determine whether these bats move
      terrestrially the way other quadrupeds do, or whether they possess altogether
      different patterns of movement on the ground than are observed in quadrupeds that
      do not fly. Using high-speed video analyses of bats moving on a treadmill, we
      observed that both species possess symmetrical lateral-sequence gaits similar to
      the kinematically defined walks of a broad range of tetrapods. At high speeds, D.
      rotundus use an asymmetrical bounding gait that appears to converge on the
      bounding gaits of small terrestrial mammals, but with the roles of the forelimbs
      and hindlimbs reversed. This gait was not performed by M. tuberculata. Many
      animals that possess a single kinematic gait shift with increasing speed from a
      kinetic walk (where kinetic and potential energy of the centre of mass oscillate
      out of phase from each other) to a kinetic run (where they oscillate in phase).
      To determine whether the single kinematic gait of M. tuberculata meets the
      kinetic definition of a walk, a run, or a gait that functions as a walk at low
      speed and a run at high speed, we used force plates and high-speed video
      recordings to characterize the energetics of the centre of mass in that species.
      Although oscillations in kinetic and potential energy were of similar magnitudes,
      M. tuberculata did not use pendulum-like exchanges of energy between them to the
      extent that many other quadrupedal animals do, and did not transition from a
      kinetic walk to kinetic run with increasing speed. The gait of M. tuberculata is
      kinematically a walk, but kinetically run-like at all speeds.

PMID- 16621954
TI  - Rapid increase in the partial pressure of NH3 on the cutaneous surface of air
      exposed mangrove killifish, Rivulus marmoratus.
AB  - Mangrove killifish, Rivulus marmoratus, are tolerant of prolonged periods of air
      exposure (>30 days). Air-exposed R. marmoratus eliminate more than 40% of their
      total ammonia through NH(3) volatilization; however, the sites and mechanisms are
      unclear. We hypothesized that the cutaneous surface is an important site of NH(3)
      volatilization in air-exposed R. marmoratus. Ion-selective microelectrodes were
      used to measure the NH(4)(+) concentration and pH in the boundary layer on the
      cutaneous surface of fish in water or air (acute: 1 h, chronic: 11 days).
      Following acute and chronic air exposure, there was a approximately 18-fold
      increase in the NH(4)(+) concentration and a 0.3-0.6 pH unit increase on the
      cutaneous surface of R. marmoratus. In air-exposed fish, the calculated cutaneous
      partial pressure (P(NH(3))) was 608-1,251 microTorr, representing a 33- to 75
      fold increase over control (immersed) fish. The P(NH(3)) on the cutaneous surface
      water film was more than sufficient to account for the rate of NH(3)
      volatilization under terrestrial conditions. Together, these data indicate that
      during air exposure, R. marmoratus utilize the cutaneous surface as a key site of
      NH(3) volatilization.

PMID- 16621955
TI  - Beyond the central pattern generator: amine modulation of decision-making neural
      pathways descending from the brain of the medicinal leech.
AB  - The biological mechanisms of behavioral selection, as it relates to locomotion,
      are far from understood, even in relatively simple invertebrate animals. In the
      medicinal leech, Hirudo medicinalis, the decision to swim is distributed across
      populations of swim-activating and swim-inactivating neurons descending from the
      subesophageal ganglion of the compound cephalic ganglion, i.e. the brain. In the
      present study, we demonstrate that the serotonergic LL and Retzius cells in the
      brain are excited by swim-initiating stimuli and during spontaneous swim
      episodes. This activity likely influences or resets the neuromodulatory state of
      neural circuits involved in the activation or subsequent termination of
      locomotion. When serotonin (5-HT) was perfused over the brain, multi-unit
      recordings from descending brain neurons revealed rapid and substantial
      alterations. Subsequent intracellular recordings from identified command-like
      brain interneurons demonstrated that 5-HT, especially in combination with
      octopamine, inhibited swim-triggering neuron Tr1, as well as swim-inactivating
      neurons Tr2 and SIN1. Although 5-HT inhibited elements of the swim-inactivation
      pathway, rather than promoting them, the indirect and net effect of the amine was
      a reliable and sustained reduction in the firing of the segmental swim-gating
      neuron 204. This modulation caused cell 204 to relinquish its excitatory drive to
      the swim central pattern generator. The activation pattern of serotonergic brain
      neurons that we observed during swimming and the 5-HT-immunoreactive staining
      pattern obtained, suggest that within the head brain 5-HT secretion is massive.
      Over time, 5-HT secretion may provide a homeostatic feedback mechanism to limit
      swimming activity at the level of the head brain.

PMID- 16621956
TI  - Spectral selectivity during phonotaxis: a comparative study in Neoconocephalus
      (Orthoptera: Tettigoniidae).
AB  - The calls of male Neoconocephalus have most energy concentrated in a relatively
      narrow low-frequency band. In N. robustus this low-frequency band is centered
      around 7 kHz, whereas calls of N. nebrascensis and N. bivocatus have center
      frequencies close to 10 kHz. The importance of the position of the low-frequency
      band for female phonotaxis in these three species was determined using a walking
      compensator. Female N. robustus showed significant phonotaxis towards call
      frequencies from 5 to 10 kHz, and spectral selectivity towards higher frequencies
      did not change with stimulus amplitude. Significant responses in N. nebrascensis
      and N. bivocatus occurred at significantly higher frequency ranges than in N.
      robustus. In these species, spectral selectivity changed with stimulus amplitude;
      at 68 dB sound pressure level (SPL), upper cut-off frequency was significantly
      lower than at 80 dB SPL in both species. Adding a higher harmonic to the
      conspecific carrier frequency had a strong inhibitory effect on phonotaxis in N.
      robustus: at higher relative amplitudes of the harmonic, phonotaxis was
      completely suppressed. Adding a higher harmonic to the conspecific carrier
      frequency had a much weaker but significant inhibitory effect in N. nebrascensis
      and little, if any, effect in N. bivocatus. The processing of song spectrum in
      the sensory system is discussed with regard to the differences in spectral
      selectivity among the three species. The sharp spectral selectivity of N.
      robustus is interpreted as an adaptation for species isolation.

PMID- 16621957
TI  - Regulation of the mitogen-activated protein kinase p44 ERK activity during
      anoxia/recovery in rainbow trout hypodermal fibroblasts.
AB  - It is well known from various mammalian cells that anoxia has a major impact on
      the mitogen-activated protein kinase ERK, but a possible similar effect in fish
      cells has not been investigated. Here we characterise a p44ERK-like protein in
      the rainbow trout cell line RTHDF and study the effect of (i) serum stimulation,
      (ii) sodium azide (chemical anoxia) and removal of azide (recovery) and (iii)
      anoxia (P(O)2<0.1%) and recovery. During both chemical and true anoxia p44ERK was
      inhibited and recovery resulted in robust reactivation of p44ERK activity, far
      above the initial level. The inhibition was secondary to activation of p38(MAPK)
      and the increase was MEK dependent, as SB203580 inhibited the dephosphorylation
      during anoxia and the presence of PD98059 inhibited phosphorylation of p44ERK
      during recovery. In addition, we demonstrated that the reactivation of p44ERK
      during recovery also was dependent on reactive oxygen species and a PP1/PP2A-like
      phosphatase.

PMID- 16621958
TI  - The role of visual cues in directed aerial descent of Cephalotes atratus workers
      (Hymenoptera: Formicidae).
AB  - Animals often depend on properties of reflected light (e.g. color, brightness) to
      locate resources. We compared reflectance properties of tree trunks with
      surrounding vegetation, and examined how differences in reflectance profiles of
      surrogate tree trunks (red, yellow, green, blue, black, gray, dark gray and white
      sheets) affected the directed aerial descent of worker Cephalotes atratus (L.)
      ants. Across the visual spectrum, tree trunk reflectance was 2-10 times higher
      than the surrounding foliage and differed among trees. In two separate
      experiments, one with colored sheets and one with black, white and gray sheets,
      nearly half (42% and 47%, respectively) of falling ants directed their descent to
      a bright white sheet when given a choice of target colors or shades of gray. When
      colored and gray sheets were presented individually, landing frequencies were
      lower than expected for all except white sheets. Glide performance was highly
      variable, but there was a tendency for higher glide indices to be associated with
      the white sheet relative to the green sheet. We conclude that visually mediated
      aerial behavior in falling canopy ants is strongly influenced by reflectance
      properties of the target object, specifically brightness, and correlates with
      preferred natural targets of tree trunks.

PMID- 16621959
TI  - In-tandem insight from basic science combined with clinical research: CD38 as
      both marker and key component of the pathogenetic network underlying chronic
      lymphocytic leukemia.
AB  - The absence of mutations in the IgV genes, together with the presence of ZAP-70
      and CD38, are the most reliable negative prognostic markers for chronic
      lymphocytic leukemia (CLL) patients. Several lines of evidence indicate that CD38
      may be not only a diagnostic marker but also a key element in the pathogenetic
      network in CLL. First, CD38 is a receptor that induces proliferation and
      increases survival of CLL cells. Second, CD38 signals start upon interaction with
      the CD31 ligand expressed by stromal and nurse-like cells. Third, CD38/CD31
      contacts up-regulate CD100, a semaphorin involved in sustaining CLL growth.
      Fourth, evidence that nurselike cells express high levels of CD31 and plexin-B1,
      the high-affinity ligand for CD100, offers indirect confirmation for this model
      of receptor cross-talk. Elements of variation in the clinical course of CD38(+)
      CLL patients include (1) potential intersection with ZAP-70, a kinase involved in
      the CD38 signaling pathway in T and natural killer (NK) cells, and (2) the
      effects of genetic polymorphisms of the receptors involved, at least of CD38 and
      CD31. Consequently, CD38 together with ZAP-70 appear to be the key elements of a
      coreceptor pathway that may sustain the signals mediated by the B-cell receptor
      and potentially by chemokines and their receptors. This would result in
      acquisition of increased survival potential, providing clues to the poorer
      prognosis of CD38(+) patients.

PMID- 16621960
TI  - The Src kinase Lyn is required for CCR5 signaling in response to MIP-1beta and R5
      HIV-1 gp120 in human macrophages.
AB  - CCR5 is a receptor for several beta chemokines and the entry coreceptor used by
      macrophage-tropic (R5) strains of HIV-1. In addition to supporting viral entry,
      CCR5 ligation by the HIV-1 envelope glycoprotein 120 (gp120) can activate
      intracellular signals in macrophages and trigger inflammatory mediator release.
      Using a combination of in vitro kinase assay, Western blotting for phospho
      specific proteins, pharmacologic inhibition, CCR5 knockout (CCR5Delta32) cells,
      and kinase-specific blocking peptide, we show for the first time that signaling
      through CCR5 in primary human macrophages is linked to the Src kinase Lyn.
      Stimulation of human monocyte-derived macrophages with either HIV-1 gp120 or MIP
      1beta results in the CCR5-mediated activation of Lyn and the concomitant Lyn
      dependent activation of the mitogen-activated protein (MAP) kinase ERK-1/2.
      Furthermore, activation of the CCR5/Lyn/ERK-1/2 pathway is responsible for gp120
      triggered production of TNF-alpha by macrophages, which is believed to contribute
      to HIV-1 pathogenesis. Thus, Lyn kinase may play an important role both in normal
      CCR5 function in macrophages and in AIDS pathogenesis in syndromes such as AIDS
      dementia where HIV-1 gp120 contributes to inappropriate macrophage activation,
      mediator production, and secondary injury.

PMID- 16621961
TI  - Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin
      lymphoma.
AB  - Pesticides have been specifically associated with the t(14;18)(q32;q21)
      chromosomal translocation. To investigate whether the association between
      pesticides and risk of non-Hodgkin lymphoma (NHL) differs for molecular subtypes
      of NHL defined by t(14; 18) status, we obtained 175 tumor blocks from case
      subjects in a population-based case-control study conducted in Nebraska between
      1983 and 1986. The t(14;18) was determined by interphase fluorescence in situ
      hybridization in 172 of 175 tumor blocks. We compared exposures to insecticides,
      herbicides, fungicides, and fumigants in 65 t(14;18)-positive and 107 t(14;18)
      negative case subjects with those among 1432 control subjects. Multivariate
      polytomous logistic regression was used to calculate odds ratios (ORs) and 95%
      confidence intervals (CIs). Compared with farmers who never used pesticides, the
      risk of t(14;18)-positive NHL was significantly elevated among farmers who used
      animal insecticides (OR = 2.6; 95% CI, 1.0-6.9), crop insecticides (OR = 3.0; 95%
      CI, 1.1-8.2), herbicides (OR = 2.9; 95% CI, 1.1-7.9), and fumigants (OR = 5.0;
      95% CI, 1.7-14.5). None of these pesticides were associated with t(14;18)
      negative NHL. The risk of t(14;18)-positive NHL associated with insecticides and
      herbicides increased with longer duration of use. We conclude that insecticides,
      herbicides, and fumigants were associated with risk of t(14;18)-positive NHL but
      not t(14;18)-negative NHL. These results suggest that defining subsets of NHL
      according to t(14;18) status is a useful approach for etiologic research.

PMID- 16621962
TI  - ULBPs, human ligands of the NKG2D receptor, stimulate tumor immunity with
      enhancement by IL-15.
AB  - ULBPs are human ligands for NKG2D, an activating receptor expressed on natural
      killer (NK) cells, NK1.1(+) T cells, and T cells. ULBPs are expressed by a
      variety of leukemias, carcinomas, melanomas, and tumor cell lines. ULBP
      expression correlates with improved survival in cancer patients, however, the
      nature of the immune response that ULBPs elicit is not well understood. We report
      that ectopic expression of ULBP1 or ULBP2 on murine EL4 or RMA tumor cells
      elicits potent antitumor responses in syngeneic C57BL/6 and SCID mice. Although
      binding of ULBP3 to murine NKG2D could not be demonstrated in vitro, ULBP3 can
      also stimulate antitumor responses, suggesting that ULBP3 binds to murine NKG2D
      or possibly another receptor in vivo. ULBP expression was found to recruit NK
      cells, NK1.1(+) T cells, and T cells to the tumor. IL-15 was found to strongly
      enhance the immune response directed against ULBP-expressing tumors. Tumors can
      evade NKG2D immunity by down-regulating expression of NKG2D. Our data suggest
      that IL-15 may be useful for overcoming this tumor-evasion strategy. Together,
      these results demonstrate that ULBP expression can elicit a potent immune
      response and suggest that ULBPs, alone or in combination with IL-15, can be
      exploited for antitumor therapy.

PMID- 16621963
TI  - Antigen targeting to endosomal pathway in dendritic cell vaccination activates
      regulatory T cells and attenuates tumor immunity.
AB  - Lymphoma cells are malignant cells of the T- or B-cell lineage that often express
      many surface markers inappropriately, yet are not recognized as abnormal by the
      immune system. We modeled this situation by inoculating ovalbumin-expressing E.G7
      OVA lymphoma cells into mice that expressed ovalbumin as a self antigen in
      pancreatic islets, and investigated the efficacy of dendritic cell (DC)
      vaccination in these mice. Although vaccination with DC-expressing ovalbumin
      induced strong cytotoxic T-cell immunity, which led to clearance of E.G7-OVA
      lymphoma cells in naive C57BL/6 mice, DC vaccination was ineffective in mice
      expressing ovalbumin as a self antigen. Antigen modification to increase its
      processing via the endosomal processing pathway dramatically increased CD4 T-cell
      activation but paradoxically, impaired the protective effect of DC vaccination
      even in naive mice. Depletion of CD25(+) T cells (regulatory T cells [Tregs])
      prior to vaccination restored the efficacy of DC vaccination and allowed
      eradication of lymphoma also in mice expressing ovalbumin as a self antigen. We
      conclude that lymphoma cells may be eradicated using DC vaccination if activation
      of CD25(+) Tregs is simultaneously inhibited, and that intentionally enhanced
      endosomal antigen processing in DC vaccines may shift the balance from CD4 T-cell
      help toward stimulation of Tregs.

PMID- 16621965
TI  - Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical
      presentation, response to treatment, and outcome.
AB  - Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy with
      manifestations of hemolytic anemia, thrombocytopenia, and renal impairment.
      Genetic studies have shown that mutations in complement regulatory proteins
      predispose to non-Shiga toxin-associated HUS (non-Stx-HUS). We undertook genetic
      analysis on membrane cofactor protein (MCP), complement factor H (CFH), and
      factor I (IF) in 156 patients with non-Stx-HUS. Fourteen, 11, and 5 new
      mutational events were found in MCP, CFH, and IF, respectively. Mutation
      frequencies were 12.8%, 30.1%, and 4.5% for MCP, CFH, and IF, respectively. MCP
      mutations resulted in either reduced protein expression or impaired C3b binding
      capability. MCP-mutated patients had a better prognosis than CFH-mutated and
      nonmutated patients. In MCP-mutated patients, plasma treatment did not impact the
      outcome significantly: remission was achieved in around 90% of both plasma
      treated and plasma-untreated acute episodes. Kidney transplantation outcome was
      favorable in patients with MCP mutations, whereas the outcome was poor in
      patients with CFH and IF mutations due to disease recurrence. This study
      documents that the presentation, the response to therapy, and the outcome of the
      disease are influenced by the genotype. Hopefully this will translate into
      improved management and therapy of patients and will provide the way to design
      tailored treatments.

PMID- 16621967
TI  - Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial
      cell survival and migration.
AB  - Neuropilin 2 (NRP2) is a receptor for the vascular endothelial growth factor
      (VEGF) and the semaphorin (SEMA) families, 2 unrelated ligand families involved
      in angiogenesis and neuronal guidance. NRP2 specifically binds VEGF-A and VEGF-C,
      although the biological relevance of these interactions in human endothelial
      cells is poorly understood. In this study, we show that both VEGF-A and VEGF-C
      induce the interaction of NRP2 with VEGFR-2. This interaction correlated with an
      enhancement of the VEGFR-2 phosphorylation threshold. Overexpression of NRP2 in
      primary human endothelial cells promoted cell survival induced by VEGF-A and VEGF
      C. In contrast, SEMA3F, another ligand for NRP2, was able to inhibit human
      endothelial cell survival and migration induced by VEGF-A and VEGF-C. Moreover, a
      siRNA targeting specifically NRP2 was a potent inhibitor of human endothelial
      cell migration induced by VEGF-A and VEGF-C. Thus, our data indicate that NRP2
      acts as a coreceptor that enhances human endothelial cell biological responses
      induced by VEGF-A and VEGF-C.

PMID- 16621968
TI  - Detection of serum hepcidin in renal failure and inflammation by using
      ProteinChip System.
AB  - Hepcidin, a key regulator of iron metabolism, is expressed in the liver,
      distributed in blood, and excreted in urine. However, to date, no reliable and
      practical method for measuring the bioactive form of hepcidin in serum has been
      developed. Here, we used surface-enhanced laser desorption ionization time of
      flight mass spectrometry (SELDI-TOF MS) to analyze the distinctive serum
      proteomic patterns of patients receiving hemodialysis. In the range of 1000 to
      15,000 m/z, we found 3 peptides at 2192, 2789, and 2851 m/z that showed a
      significant correlation with the serum ferritin levels. The molecular sizes of
      peptides at 2192 and 2789 m/z matched with the reported sizes of hepcidin-20 and 
      25, respectively, and the serum peptide at 2789 m/z was identified as hepcidin-25
      by collision-induced dissociation tandem MS. By using SELDI-TOF MS, we developed
      a semiquantitative assay for hepcidin-25. In this assay, the level of serum
      hepcidin-25 correlated well with levels of serum ferritin and serum interleukin
      6. Hepcidin-25 was found to accumulate in the serum of patients receiving
      hemodialysis; this could contribute to the pathogenesis of renal anemia by
      decreasing the available iron for hematopoiesis. Thus, SELDI-TOF MS would be a
      clinically useful tool to detect and semiquantify bioactive hepcidin in serum.

PMID- 16621969
TI  - Transcriptional regulatory networks downstream of TAL1/SCL in T-cell acute
      lymphoblastic leukemia.
AB  - Aberrant expression of 1 or more transcription factor oncogenes is a critical
      component of the molecular pathogenesis of human T-cell acute lymphoblastic
      leukemia (T-ALL); however, oncogenic transcriptional programs downstream of T-ALL
      oncogenes are mostly unknown. TAL1/SCL is a basic helix-loop-helix (bHLH)
      transcription factor oncogene aberrantly expressed in 60% of human T-ALLs. We
      used chromatin immunoprecipitation (ChIP) on chip to identify 71 direct
      transcriptional targets of TAL1/SCL. Promoters occupied by TAL1 were also
      frequently bound by the class I bHLH proteins E2A and HEB, suggesting that
      TAL1/E2A as well as TAL1/HEB heterodimers play a role in transformation of T-cell
      precursors. Using RNA interference, we demonstrated that TAL1 is required for the
      maintenance of the leukemic phenotype in Jurkat cells and showed that TAL1
      binding can be associated with either repression or activation of genes whose
      promoters occupied by TAL1, E2A, and HEB. In addition, oligonucleotide microarray
      analysis of RNA from 47 primary T-ALL samples showed specific expression
      signatures involving TAL1 targets in TAL1-expressing compared with -nonexpressing
      human T-ALLs. Our results indicate that TAL1 may act as a bifunctional
      transcriptional regulator (activator and repressor) at the top of a complex
      regulatory network that disrupts normal T-cell homeostasis and contributes to
      leukemogenesis.

PMID- 16621970
TI  - Expression and purification of functional ligand-binding domains of T1R3 taste
      receptors.
AB  - Chemosensory receptors, including odor, taste, and vomeronasal receptors,
      comprise the largest group of G protein-coupled receptors (GPCRs) in the
      mammalian genome. However, little is known about the molecular determinants that
      are critical for the detection and discrimination of ligands by most of these
      receptors. This dearth of understanding is due in part to difficulties in
      preparing functional receptors suitable for biochemical and biophysical analyses.
      Here we describe in detail two strategies for the expression and purification of
      the ligand-binding domain of T1R taste receptors, which are constituents of the
      sweet and umami taste receptors. These class C GPCRs contain a large
      extracellular N-terminal domain (NTD) that is the site of interaction with most
      ligands and that is amenable to expression as a separate polypeptide in
      heterologous cells. The NTD of mouse T1R3 was expressed as two distinct fusion
      proteins in Escherichia coli and purified by column chromatography. Spectroscopic
      analysis of the purified NTD proteins shows them to be properly folded and
      capable of binding ligands. This methodology should not only facilitate the
      characterization of T1R ligand interactions but may also be useful for dissecting
      the function of other class C GPCRs such as the large family of orphan V2R
      vomeronasal receptors.

PMID- 16621971
TI  - Electrophysiological and behavioral responses of a parasitic wasp to plant
      volatiles induced by two leaf miner species.
AB  - In the present study, Y-tube olfactometric assays demonstrated that headspace
      volatile extracts collected from leaf miner-damaged, or artificially damaged,
      bean plants were more attractive to naive females of the parasitoid insect Opius
      dissitus than those collected from healthy plants. Headspace extracts from both
      Liriomyza huidobrensis and Liriomyza sativae second-instar larvae-damaged beans
      were analyzed by coupled gas chromatography-electroantennographic detection (GC
      EAD). Of nine EAD-active volatiles identified, (3E)-4,8-dimethyl-1,3,7
      nonatriene, (3Z)-hexenyl acetate, (syn)-2-methylpropanal oxime, and (syn)-2
      methylbutanal oxime were the most abundant compounds that evoked significant
      electroantennogram (EAG) responses. Compounds (3Z)-hexen-1-ol, (anti)-2
      methylbutanal oxime, linalool, beta-caryophyllene, and (3E,7E)-4,8,12-trimethyl
      1,3,7,11-tridecatetraene also elicited clear EAG responses but were present in
      smaller amounts. Choice experiments in a Y-tube olfactometer indicated that
      synthetic versions of (3Z)-hexen-1-ol, 2-methylpropanal oxime, 2-methylbutanal
      oxime, 3-methylbutanal oxime, linalool, (E,E)-alpha-farnesene, and (3E,7E)-4,8,12
      trimethyl-1,3,7,11-tridecatetraene were attractive individually, while (3Z)
      hexenyl acetate and (3E)-4,8-dimethyl-1,3,7-nonatriene were unattractive at
      concentrations similar to those obtained from the headspace collection. Moreover,
      a blend of nine EAD-active volatiles was significantly more attractive relative
      to hexane (solvent). A mixture of oximes, tereponids, and green leaf volatiles
      may facilitate host location by female O. dissitus.

PMID- 16621972
TI  - Response to comment on "Cathepsin-L influences the expression of extracellular
      matrix in lymphoid organs and plays a role in the regulation of thymic output and
      of peripheral T cell number".

PMID- 16621974
TI  - Comment on "Analysis of the cellular mechanism of antitumor responses and
      autoimmunity in patients treated with CTLA-4 blockade".

PMID- 16621975
TI  - Comment on "Pretreatment intracerebral and peripheral blood immune responses in
      Vietnamese adults with tuberculous meningitis: diagnostic value and relationship
      to disease severity and outcome".

PMID- 16621976
TI  - When it comes to CTL recognition, size does matter.

PMID- 16621977
TI  - The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can
      be defined with short synthetic peptides. 1986.

PMID- 16621978
TI  - The multiple personalities of the chemokine receptor CCR7 in dendritic cells.
AB  - CCR7 was described initially as a potent leukocyte chemotactic receptor that was
      later shown to be responsible of directing the migration of dendritic cells (DCs)
      to the lymph nodes where these cells play an important role in the initiation of
      the immune response. Recently, a variety of reports have indicated that, apart
      from chemotaxis, CCR7 controls the cytoarchitecture, the rate of endocytosis, the
      survival, the migratory speed, and the maturation of the DCs. Some of these
      functions of CCR7 and additional ones also have been described in other cell
      types. Herein we discuss how this receptor may contribute to modulate the immune
      response by regulating different functions in DCs. Finally, we also suggest a
      possible mechanism whereby CCR7 may control its multiple tasks in these cells.

PMID- 16621979
TI  - Cutting Edge: Inhibition of the retinoid X receptor (RXR) blocks T helper 2
      differentiation and prevents allergic lung inflammation.
AB  - Among the many factors regulating Th cell differentiation, some nuclear hormone
      receptors are emerging as important players. The retinoid X receptor (RXR)
      functions as heterodimerization partner for a variety of nuclear hormone
      receptors. We show in this study that RXR is critical for Th2-mediated immunity.
      An RXR antagonist inhibited Th2 differentiation, resulting in reduced production
      of IL-4, IL-10, and IL-13, whereas IFN-gamma production was enhanced. This effect
      was dependent on the presence of APCs. In addition, IL-5 production was blocked
      directly in Th cells. In vivo, inhibition of RXR prevented experimentally induced
      allergic lung inflammation. Th1-mediated inflammation was not affected. Its
      specific role in Th2-mediated inflammation makes RXR a promising target for the
      development of therapies against diseases such as allergic asthma and atopic
      dermatitis.

PMID- 16621980
TI  - Cutting Edge: Lentiviral short hairpin RNA silencing of PTEN in human mast cells
      reveals constitutive signals that promote cytokine secretion and cell survival.
AB  - Engagement of the FcepsilonRI expressed on mast cells induces the production of
      phosphatidylinositol 3, 4, 5-trisphosphate by PI3K, which is essential for the
      functions of the cells. PTEN (phosphatase and tensin homologue deleted on
      chromosome ten) directly opposes PI3K by dephosphorylating phosphatidylinositol
      3, 4, 5-trisphosphate at the 3' position. In this work we used a lentivirus
      mediated short hairpin RNA gene knockdown method to study the role of PTEN in
      CD34(+) peripheral blood-derived human mast cells. Loss of PTEN caused
      constitutive phosphorylation of Akt, p38 MAPK, and JNK, as well as cytokine
      production and enhancement in cell survival, but not degranulation. FcepsilonRI
      engagement of PTEN-deficient cells augmented signaling downstream of Src kinases
      and increased calcium flux, degranulation, and further enhanced cytokine
      production. PTEN-deficient cells, but not control cells, were resistant to
      inhibition of cytokine production by wortmannin, a PI3K inhibitor. The findings
      demonstrate that PTEN functions as a key regulator of mast cell homeostasis and
      FcepsilonRI-responsiveness.

PMID- 16621981
TI  - Mycobacteria induce IFN-gamma production in human dendritic cells via triggering
      of TLR2.
AB  - IFN-gamma is of central importance for the induction of robust cell-mediated
      immunity and for the activation of APC. Recent studies using experimental murine
      systems have now suggested a fundamental role for APC-derived IFN-gamma during
      infection with intracellular pathogens. It is currently unknown whether human
      dendritic cells (DC) can respond to bacterial stimulation with production of IFN
      gamma. To test this question, we used human monocyte-derived DC stimulated by
      Mycobacterium bovis bacillus Calmette-Guerin as a model system. We demonstrate
      production of IFN-gamma mRNA and protein on the single cell level. IFN-gamma in
      DC cultures was not simply produced by contaminating lymphocytes because
      production of DC-IFN-gamma could also be demonstrated in highly purified DC
      cultures containing virtually no T, B, and NK cells. TLR2 was identified as a key
      receptor involved in triggering production of DC-IFN-gamma. Interestingly, DC-IFN
      gamma seems to participate in an autocrine DC activation loop, and production of
      DC-IFN-gamma could be enhanced by costimulation of DC with IL-12/IL-15/IL-18. In
      conclusion, we have demonstrated production of IFN-gamma by human DC on the
      single cell level, identified TLR2 as a pattern recognition receptor involved in
      this process, and elucidated some of the functional consequences of autocrine IFN
      gamma production by human DC.

PMID- 16621982
TI  - Selection of anti-double-stranded DNA B cells in autoimmune MRL-lpr/lpr mice.
AB  - Abs to DNA and nucleoproteins are expressed in systemic autoimmune diseases,
      whereas B cells producing such Abs are edited, deleted, or inactivated in healthy
      individuals. Why autoimmune individuals fail to regulate is not well understood.
      In this study, we investigate the sources of anti-dsDNA B cells in autoimmune
      transgenic MRL-lpr/lpr mice. These mice are particularly susceptible to lupus
      because they carry a site-directed transgene, H76R that codes for an anti-DNA H
      chain. Over 90% of the B cells are eliminated in the bone marrow of these mice,
      and the few surviving B cells are associated with one of two Vkappa editors,
      Vkappa38c and Vkappa21D. Thus, it appears that negative selection by deletion and
      editing are intact in MRL-lpr/lpr mice. However, a population of splenic B cells
      in the H76R MRL-lpr/lpr mice produces IgG anti-nuclear Abs, and these mice have
      severe autoimmune organ damage. These IgG Abs are not associated with editors but
      instead use a unique Vkappa gene, Vkappa23. The H76R/Vkappa23 combination has a
      relatively high affinity for dsDNA and an anti-nuclear Ab pattern characteristic
      of lupus. Therefore, this Vkappa gene may confer a selective advantage to anti
      DNA Abs in diseased mice.

PMID- 16621983
TI  - Dendritic cells require multidrug resistance protein 1 (ABCC1) transporter
      activity for differentiation.
AB  - Dendritic cells (DC) express the ATP-binding cassette (ABC) transporters P
      glycoprotein (ABCB1) and multidrug resistance protein 1 (MRP1; ABCC1).
      Functionally, both these transporters have been described to be required for
      efficient DC and T cell migration. In this study, we report that MRP1 activity is
      also crucial for differentiation of DC. Inhibition of MRP1, but not P
      glycoprotein, transporter activity with specific antagonists during in vitro DC
      differentiation interfered with early DC development. Impaired interstitial and
      Langerhans DC differentiation was characterized by 1) morphological changes,
      reflected by dropped side scatter levels in flow cytometric analysis and 2)
      phenotypic changes illustrated by maintained expression of the monocytic marker
      CD14, lower expression levels of CD40, CD86, HLA-DR, and a significant decrease
      in the amount of cells expressing CD1a, CD1c, and Langerin. Defective DC
      differentiation also resulted in their reduced ability to stimulate allogeneic T
      cells. We identified the endogenous CD1 ligands sulfatide and
      monosialoganglioside GM1 as MRP1 substrates, but exogenous addition of these
      substrates could not restore the defects caused by blocking MRP1 activity during
      DC differentiation. Although leukotriene C(4) was reported to restore migration
      of murine Mrp1-deficient DC, the effects of MRP1 inhibition on DC differentiation
      appeared to be independent of the leukotriene pathway. Though MRP1 transporter
      activity is important for DC differentiation, the relevant MRP1 substrate, which
      is required for DC differentiation, remains to be identified. Altogether, MRP1
      seems to fulfill an important physiological role in DC development and DC
      functions.

PMID- 16621984
TI  - Detection and characterization of hemopoietic stem cells in the adult human small
      intestine.
AB  - The concept of lymphoid differentiation in the human gastrointestinal tract is
      controversial but is the focus of this study, which examined adult human small
      intestinal tissue for the presence of CD34(+)CD45(+) hemopoietic stem cells
      (HSCs) and lymphoid progenitors. Flow cytometry demonstrated that over 5% of
      leukocytes (CD45(+) cells) isolated from human gut were HSCs coexpressing CD34, a
      significantly higher incidence than in matched peripheral blood or control bone
      marrow. HSCs were detected in cell preparations from both the epithelium and
      lamina propria of all samples tested and localized to the intestinal villous and
      crypt regions using immunofluorescence. A high proportion of gut HSCs expressed
      the activation marker CD45RA, and few expressed c-kit, indicating ongoing
      differentiation. The vast majority of intestinal HSCs coexpressed the T cell Ag,
      CD7 (92% in the epithelium, 80% in the lamina propria) whereas <10% coexpressed
      the myeloid Ag CD33, suggesting that gut HSCs are a relatively mature population
      committed to the lymphoid lineage. Interestingly, almost 50% of epithelial layer
      HSCs coexpressed CD56, the NK cell Ag, compared with only 10% of the lamina
      propria HSC population, suggesting that the epithelium may be a preferential site
      of NKR(+) lymphoid differentiation. In contrast, bone marrow HSCs displayed low
      coexpression of CD56 and CD7 but high coexpression of CD33. The phenotype of
      intestinal HSCs, which differs significantly from circulating or bone marrow
      HSCs, is consistent with a role in local lymphoid development.

PMID- 16621985
TI  - Regulation of intestinal dendritic cell migration and activation by plasmacytoid
      dendritic cells, TNF-alpha and type 1 IFNs after feeding a TLR7/8 ligand.
AB  - Dendritic cells (DCs) migrating via lymph are the primary influence regulating
      naive T cell differentiation, be it active immunity or tolerance. How DCs achieve
      this regulation in vivo is poorly understood. Intestinal DCs are in direct
      contact with harmless or pathogenic luminal contents, but may also be influenced
      by signals from epithelial cells, macrophages, or other resident or immigrant
      cells. To understand the role of TLR7 and TLR8 in regulating intestinal DC
      function, we fed a TLR7/8 ligand (resiquimod (R-848)) to rats and mice and
      examined DC in pseudoafferent lymph (rat) and mesenteric lymph nodes (MLNs). Oral
      R-848 induced a 20- to 30-fold increase in DC output from the intestine within 10
      h due to a virtually total release of lamina propria DCs. This resulted in an
      accumulation of DCs in the MLNs that in mice was completely TNF-alpha dependent.
      Surprisingly, intestinal lymph DCs (iL-DCs) released by R-848 did not up-regulate
      CD86, but did up-regulate CD25. In contrast, MLN-DCs from R-848-stimulated rats
      and mice expressed high levels of CD86. This DC activation in MLNs was dependent
      on type 1 IFNs. The major source of these rapidly released cytokines is
      plasmacytoid DCs (pDCs) and not classical DCs, because depletion of pDCs
      significantly reduces the R-848-stimulated increase in serum cytokine levels as
      well as the accumulation and activation of DCs in MLNs. These experiments show
      that TLR-mediated regulation of iL-DC functions in vivo is complex and does not
      depend only on direct iL-DC stimulation, but can be regulated by pDCs.

PMID- 16621987
TI  - Conversion of alloantigen-specific CD8+ T cell anergy to CD8+ T cell priming
      through in vivo ligation of glucocorticoid-induced TNF receptor.
AB  - In this study, we investigated the effect of an agonistic mAb (DTA-1) against
      glucocorticoid-induced TNF receptor (GITR) in a murine model of systemic lupus
      erythematosus-like chronic graft-vs-host disease (cGVHD). A single dose of DTA-1
      inhibited the production of anti-DNA IgG1 autoantibody and the development of
      glomerulonephritis, typical symptoms of cGVHD. DTA-1-treated mice showed clinical
      and pathological signs of acute GVHD (aGVHD), such as lymphopenia, loss of body
      weight, increase of donor cell engraftment, and intestinal damage, indicating
      that DTA-1 shifted cGVHD toward aGVHD. The conversion of cGVHD to aGVHD occurred
      because DTA-1 prevented donor CD8+ T cell anergy. Functionally active donor CD8+
      T cells produced high levels of IFN-gamma and had an elevated CTL activity
      against host Ags. In in vitro MLR, anergic responder CD8+ T cells were generated,
      and DTA-1 stimulated the activation of these anergic CD8+ T cells. We further
      confirmed in vivo that donor CD8+ T cells, but not donor CD4+ T cells, were
      responsible for the DTA-1-mediated conversion of cGVHD to aGVHD. These results
      indicate that donor CD8+ T cell anergy is a restriction factor in the development
      of aGVHD and that in vivo ligation of GITR prevents CD8+ T cell anergy by
      activating donor CD8+ T cells that otherwise become anergic. In sum, our data
      suggest GITR as an important costimulatory molecule regulating cGVHD vs aGVHD and
      as a target for therapeutic intervention in a variety of related diseases.

PMID- 16621986
TI  - Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant.
AB  - The promising, but modest, clinical results of many human cancer vaccines
      indicate a need for vaccine adjuvants that can increase both the quantity and the
      quality of vaccine-induced, tumor-specific T cells. In this study we tested the
      immunological and antitumor effects of the proinflammatory cytokine, IL-23, in
      gp100 peptide vaccine therapy of established murine melanoma. Neither systemic
      nor local IL-23 alone had any impact on tumor growth or tumor-specific T cell
      numbers. Upon specific vaccination, however, systemic IL-23 greatly increased the
      relative and absolute numbers of vaccine-induced CD8(+) T cells and enhanced
      their effector function at the tumor site. Although IL-23 specifically increased
      IFN-gamma production by tumor-specific T cells, IFN-gamma itself was not a
      primary mediator of the vaccine adjuvant effect. The IL-23-induced antitumor
      effect and accompanying reversible weight loss were both partially mediated by
      TNF-alpha. In contrast, local expression of IL-23 at the tumor site maintained
      antitumor activity in the absence of weight loss. Under these conditions, it was
      also clear that enhanced effector function of vaccine-induced CD8(+) T cells,
      rather than increased T cell number, is a primary mechanism underlying the
      antitumor effect of IL-23. Collectively, these results suggest that IL-23 is a
      potent vaccine adjuvant for the induction of therapeutic, tumor-specific CD8(+) T
      cell responses.

PMID- 16621989
TI  - CTLA-4 engagement and regulatory CD4+CD25+ T cells independently control CD8+
      mediated responses under costimulation blockade.
AB  - Blockade of costimulatory signals is a promising therapeutic target to prevent
      allograft rejection. In this study, we sought to characterize to what extent CTLA
      4 engagement contributes to the development of transplantation tolerance under
      the cover of CD40/CD40L and CD28/CD86 blockade. In vitro, we found that
      inhibition of the primary alloresponse and induction of alloantigen
      hyporesponsiveness by costimulation blockade was abrogated by anti-CTLA-4 mAb. In
      addition, regulatory CD4(+)CD25(+) T cells (T(REG)) were confirmed to play a
      critical role in the induction of hyporesponsiveness by anti-CD40L and anti-CD86
      mAb. Our data indicated that CTLA-4 engagement is not required for activation or
      suppressor function of T(REG). Instead, in the absence of either CTLA-4 signaling
      or T(REG), CD8(+) T cell division was enhanced, whereas the inhibition of CD4(+)
      T cell division by costimulation blockade remained largely unaffected. In vivo,
      the administration of additional anti-CTLA-4 mAb abrogated anti-CD40L- and anti
      CD86 mAb-induced cardiac allograft survival. Correspondingly, rejection was
      accompanied by enhanced allograft infiltration of CD8(+) cells. We conclude that
      CTLA-4 signaling and T(REG) independently cooperate in the inhibition of CD8(+) T
      cell expansion under costimulation blockade.

PMID- 16621988
TI  - Chlamydia infection induces ICOS ligand-expressing and IL-10-producing dendritic
      cells that can inhibit airway inflammation and mucus overproduction elicited by
      allergen challenge in BALB/c mice.
AB  - Our previous study has shown that the adoptive transfer of dendritic cells (DCs)
      freshly isolated from Chlamydia-infected mice (iIDCs), unlike those from control
      naive mice (iNDCs), can inhibit systemic and cutaneous eosinophilia induced by
      OVA exposure. In the present study, we examined the mechanism by which iIDC
      inhibits allergen-specific Th2 cell differentiation in vitro and in vivo. The
      study revealed that iIDCs exhibited higher surface expression of CD8alpha and the
      ICOS ligand (ICOS-L), as well as higher IL-10 and IL-12 production than iNDCs. In
      vitro DC:CD4(+) T cell coculture experiments showed that iIDCs could inhibit
      allergen-specific Th2 cell differentiation and that the inhibitory effect could
      be abolished by the blockage of IL-10 or IL-12 activity. More interestingly, the
      coblockade of IL-10 and the ICOS-L showed synergistic effect in enhancing
      allergen-driven Th2 cytokine production. Furthermore, adoptive transfer of iIDCs,
      but not iNDCs, to OVA sensitized mice significantly inhibited airway eosinophilia
      and mucus overproduction following intranasal challenge with OVA. Overall, the
      data demonstrate a critical role played by ICOS-L-expressing and IL-10-producing
      DCs from Chlamydia-infected mice in the infection-mediated inhibition of allergic
      responses.

PMID- 16621990
TI  - Autoreactive T cells mediate NK cell degeneration in autoimmune disease.
AB  - Emerging evidence indicates that NK cells play an important and complex role in
      autoimmune disease. Humans with autoimmune diseases often have reduced NK cell
      numbers and compromised NK cell functions. Mechanisms underlying this NK cell
      degeneration and its biological significance are not known. In this study we show
      that, in an experimental model of human autoimmune myasthenia gravis induced by a
      self-Ag, the acetylcholine receptor, NK cells undergo proliferation during the
      initiation of autoimmunity, followed by significant degeneration associated with
      the establishment of the autoreactive T cell response. We show that NK cell
      degeneration was mediated by IL-21 derived from autoreactive CD4(+) T cells, and
      that acetylcholine receptor-immunized IL-21R-deficient mice, with competent NK
      cells, developed exacerbated autoimmunity. Thus, NK cell degeneration may serve
      as a means evolved by the immune system to control excessive autoimmunity.

PMID- 16621991
TI  - Interleukin-2-dependent mechanisms of tolerance and immunity in vivo.
AB  - IL-2 is a critical T cell growth factor in vitro, but predominantly mediates
      tolerance in vivo. IL-2 is mainly produced by CD4(+) Th cells, but the role of Th
      cell-derived IL-2 in vivo is controversial. We demonstrate that during immunity
      to a tumor/self-Ag, the predominant role of Th cell-derived IL-2 was to maintain
      IL-2Ralpha (CD25) on CD4(+) T regulatory cells (T(reg)), which resulted in their
      maintenance of the T(reg) cell lineage factor, Forkhead/winged helix
      transcription factor (Foxp3), and tolerance. However, in the absence of T(reg)
      cells, Th cell-derived IL-2 maintained effector T cells and caused autoimmunity.
      IL-2R signaling was indispensable for T(reg) cell homeostasis and efficient
      suppressor function in vivo, but, surprisingly, was not required for their
      generation, because IL-2(-/-) and CD25(-/-) mice both contained Foxp3(+) T cells
      in the periphery. IL-2R signaling was also important for CD8(+) T cell immunity,
      because CD25(-/-) tumor-reactive CD8(+) T cells failed to affect established
      tumors. Conversely, IL-2R signaling was not required for Th cell function.
      Lastly, administration of anti-IL-2 plus exogenous IL-15 to tumor-bearing mice
      enhanced the adoptive immunotherapy of cancer. Therefore, Th cell-derived IL-2
      paradoxically controls both tolerance and immunity to a tumor/self-Ag in vivo.

PMID- 16621992
TI  - Notch signaling requires GATA-2 to inhibit myelopoiesis from embryonic stem cells
      and primary hemopoietic progenitors.
AB  - The bone marrow and thymus, although both hemopoietic environments, induce very
      distinct differentiation outcomes. The former supports hemopoietic stem cell self
      renewal and multiple hemopoietic lineages, while the latter supports T
      lymphopoiesis almost exclusively. This distinction suggests that the thymic
      environment acts to restrict the hemopoietic fates available to thymic
      immigrants. In this study, we demonstrate that the addition of the Notch ligand
      Delta-like-1 (Dll-1) to an in vitro system that otherwise supports myelopoiesis,
      greatly reduces the myelopoietic potential of stem cells or uncommitted
      progenitors. In contrast, committed myeloid progenitors mature regardless of the
      presence of Dll-1. The block in myelopoiesis is the direct result of Notch
      signaling within the hemopoietic progenitor, and Dll-1-induced signals cause a
      rapid increase in the expression of the zinc finger transcription factor GATA-2.
      Importantly, in the absence of GATA-2, Dll-1-induced signals fail to inhibit
      commitment to the myeloid fate. Taken together, our results support a role for
      GATA-2 in allowing Dll-1 to restrict non-T cell lineage differentiation outcomes.

PMID- 16621993
TI  - CXCR5/CXCL13 interaction is important for double-negative regulatory T cell
      homing to cardiac allografts.
AB  - Accumulating evidence indicates that regulatory T (Treg) cells control
      development of various diseases both systemically and locally. However, molecular
      mechanisms involved in Treg cell homing remain elusive. We have shown previously
      that alphabetaTCR(+)CD3(+)CD4(-)CD8(-) double-negative (DN) Treg cells
      selectively accumulate in tolerant allografts to maintain localized immune
      regulation. However, the molecular mechanism leading to the accumulation of DN
      Treg cells in tolerant grafts was not known. Our cDNA microarray analysis
      revealed significant up-regulation of chemokine receptor CXCR5 mRNA in DN Treg
      clones compared with nonregulatory clones. In this study, we examined the
      importance of CXCR5 in mediating DN Treg migration. Compared with CD4 and CD8 T
      cells, both primary DN Treg cells and clones constitutively express high levels
      of CXCR5 protein, enabling them to migrate toward increasing CXCL13 gradients in
      vitro. After infusion into recipient mice, CXCR5(+) DN Treg clones, but not their
      CXCR5(-) mutants, preferentially accumulated in cardiac allografts and could
      prevent graft rejection. Furthermore, we found that allogeneic cardiac allografts
      express high levels of CXCL13 mRNA compared with either recipient native hearts
      or nontransplanted donor hearts. Ab neutralization of CXCL13 abrogated DN Treg
      cell migration in vitro and prevented in vivo homing of DN Treg clones into
      allografts. These data demonstrate that DN Treg cells preferentially express
      CXCR5, and interaction of this chemokine receptor with its ligand CXCL13 plays an
      important role in DN Treg cell migration both in vitro and in vivo.

PMID- 16621994
TI  - Statin-induced proinflammatory response in mitogen-activated peripheral blood
      mononuclear cells through the activation of caspase-1 and IL-18 secretion in
      monocytes.
AB  - Statins, which inhibit 3-hydroxy-3-methylglutaryl CoA reductase, have been shown
      recently to promote proinflammatory responses. We show in this study that both
      atorvastatin and simvastatin induced proinflammatory responses in mitogen
      activated PBMCs by increasing the number of T cells secreting IFN-gamma. This is
      abolished by the presence of mevalonate, suggesting that statins act specifically
      by blocking the mevalonate pathway for cholesterol synthesis to promote the
      proinflammatory response. Both statins at low concentrations induced a dose
      dependent increase in the number of IFN-gamma-secreting T cells in mitogen
      activated PBMCs, whereas at higher concentrations the effect was abolished. The
      proinflammatory effect of statins was not seen in purified T cells per se
      activated with mitogen. However, conditioned medium derived from statin-treated
      PBMCs enhanced the number of IFN-gamma-secreting cells in activated purified T
      cells. This effect was not blocked by mevalonate, but was abolished by
      neutralizing Abs to IL-18 and IL-12. Similarly, the up-regulation of IFN-gamma
      secreting T cells in PBMCs costimulated with statins and mitogens was blocked by
      the neutralizing anti-IL-18 and anti-IL-12. We showed that simvastatin stimulates
      the secretion of IL-18 and IL-1beta in monocytes. Active caspase-1, which is
      required for the processing and secretion of IL-18 and IL-1beta, was activated in
      simvastatin-treated monocytes. This was blocked by mevalonate and the caspase
      inhibitor benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone. Taken together,
      the proinflammatory response mediated by statins in activated PBMCs is mediated
      mainly via the activation of caspase-1 and IL-18 secretion in the monocytes and
      to a lesser extent by IL-12.

PMID- 16621995
TI  - Human CD4+CD25high regulatory T cells modulate myeloid but not plasmacytoid
      dendritic cells activation.
AB  - Human CD4(+)CD25(+) regulatory T cells (Treg) play an essential role in the
      prevention of autoimmune diseases. However, the mechanisms of immune suppression
      and the spectrum of cells they target in vivo remain incompletely defined. In
      particular, although Treg directly suppress conventional T cells in vitro, they
      have been shown to inhibit the Ag-presenting functions of macrophage- and
      monocyte-derived dendritic cells (DC). We have now studied the maturation of
      human blood-derived myeloid DC and plasmacytoid DC activated with TLR ligands in
      the presence of Treg. Preactivated Treg suppressed strongly TLR-triggered myeloid
      DC maturation, as judged by the blocking of costimulatory molecule up-regulation
      and the inhibition of proinflammatory cytokines secretion that resulted in poor
      Ag presentation capacity. Although IL-10 played a prominent role in inhibiting
      cytokines secretion, suppression of phenotypic maturation required cell-cell
      contact and was independent of TGF-beta and CTLA-4. In contrast, the acquisition
      of maturation markers and production of cytokines by plasmacytoid DC triggered
      with TLR ligands were insensitive to regulatory T cells. Therefore, human Treg
      may enlist myeloid, but not plasmacytoid DC for the initiation and the
      amplification of tolerance in vivo by restraining their maturation after TLR
      stimulation.

PMID- 16621996
TI  - IL-4 induces in vivo production of IFN-gamma by NK and NKT cells.
AB  - Although IL-4 and IFN-gamma often have opposite effects and suppress each other's
      production by T cells, IL-4 can stimulate IFN-gamma production. To characterize
      this, we injected mice with IL-4 and quantified IFN-gamma production with the in
      vivo cytokine capture assay. IL-4 induced Stat6-dependent IFN-gamma production by
      NK and, to a lesser extent, NKT cells, but not conventional T cells, in 2-4 h.
      Increased IFN-gamma production persisted at a constant rate for >24 h, but
      eventually declined, even with continuing IL-4 stimulation. This eventual decline
      in IFN-gamma production was accompanied by a decrease in NK and T cell numbers.
      Consistent with a dominant role for NK cells in IL-4-stimulated IFN-gamma
      secretion, IL-4 induction of IFN-gamma was B and T cell-independent; suppressed
      by an anti-IL-2Rbeta mAb that eliminates most NK and NKT cells; reduced in Stat4
      deficient mice, which have decreased numbers of NK cells; and absent in
      Rag2/gamma(c)-double-deficient mice, which lack T, B, and NK cells. IL-4-induced
      IFN-gamma production was not affected by neutralizing IL-12p40 and was increased
      by neutralizing IL-2. IL-13, which signals through the type 2 IL-4R and mimics
      many IL-4 effects, failed to stimulate IFN-gamma production and, in most
      experiments, suppressed basal IFN-gamma production. Thus, IL-4, acting through
      the type 1 IL-4R, induces Stat6-dependent IFN-gamma secretion by NK and NKT
      cells. This explains how IL-4 can contribute to Th1 cytokine-associated immune
      effector functions and suggests how IL-13 can have stronger proallergic effects
      than IL-4.

PMID- 16621997
TI  - Induction of CTLA-4-mediated anergy contributes to persistent colonization in the
      murine model of gastric Helicobacter pylori infection.
AB  - Helicobacter pylori infection induces gastric inflammation but the host fails to
      generate protective immunity. Therefore, we evaluated the immunologic mechanisms
      that contribute to the failure of the T cells to promote active immunity to H.
      pylori in the mouse model of H. pylori infection. Spleen cells from infected
      C57BL/6 mice underwent significantly less proliferation and cytokine production
      than cells from immune mice upon in vitro stimulation with H. pylori lysate.
      Similar results were observed when stimulating with Ag-pulsed macrophages
      demonstrating that hyporesponsiveness was not due to a direct effect of H. pylori
      virulence factors on the T cells. Ag-specific hyporesponsiveness could be
      reversed by the addition of high-dose IL-2 but not by removal of CD4(+)CD25(+) T
      cells, indicating that hyporesponsiveness was due to anergy and not due to active
      suppression. Cells from infected mice lacked significant suppressor activity as
      shown by the failure to reduce the recall response of cells from immune mice in
      coculture at physiologic ratios. Direct blockade of CTLA-4 using anti-CTLA-4 Fabs
      or indirect blockade using CTLA-4 Ig plus anti-CD28 Ab resulted in significantly
      increased T cell activation in vitro. The importance of CTLA-4 in establishing
      anergy was confirmed in an in vivo model of H. pylori infection in which mice
      that received anti-CTLA-4 Fabs responded to H. pylori challenge with
      significantly greater inflammation and significantly reduced bacterial load.
      These results suggest that CTLA-4 engagement induces and maintains functional
      inactivation of H. pylori-specific T cells during H. pylori infection resulting
      in a reduced immune response.

PMID- 16621998
TI  - RhoG regulates the neutrophil NADPH oxidase.
AB  - RhoG is a Rho family small GTPase implicated in cytoskeletal regulation, acting
      either upstream of or in parallel to Rac1. The precise function(s) of RhoG in
      vivo has not yet been defined. We have identified a novel role for RhoG in
      signaling the neutrophil respiratory burst stimulated by G protein-coupled
      receptor agonists. Bone marrow-derived neutrophils from RhoG knockout (RhoG(-/-))
      mice exhibited a marked impairment of oxidant generation in response to C5a or
      fMLP, but normal responses to PMA or opsonized zymosan and normal bacterial
      killing. Activation of Rac1 and Rac2 by fMLP was diminished in RhoG(-/-)
      neutrophils only at very early (5 s) time points (by 25 and 32%, respectively),
      whereas chemotaxis in response to soluble agonists was unaffected by lack of
      RhoG. Additionally, fMLP-stimulated phosphorylation of protein kinase B and
      p38MAPK, activation of phospholipase D, and calcium fluxes were equivalent in
      wild-type and RhoG(-/-) neutrophils. Our results define RhoG as a critical
      component of G protein-coupled receptor-stimulated signaling cascades in murine
      neutrophils, acting either via a subset of total cellular Rac relevant to oxidase
      activation and/or by a novel and as yet undefined interaction with the neutrophil
      NADPH oxidase.

PMID- 16621999
TI  - CD72 down-modulates BCR-induced signal transduction and diminishes survival in
      primary mature B lymphocytes.
AB  - CD72, a 45-kDa type II transmembrane glycoprotein carrying an ITIM motif, is
      believed to be an inhibitory coreceptor of the BCR. Mature B cells lacking CD72
      show enhanced Ca(2+) mobilization and are hyperproliferative in response to BCR
      ligation. However, the signal transduction pathways downstream of BCR signaling
      that transmit the inhibitory effect of CD72 in mature B cells remain unknown. To
      address this question, we used hen egg lysozyme-specific BCR transgenic mice to
      elucidate the differential cell signaling between wild-type and CD72-deficient B
      cells in response to hen egg lysozyme Ag stimulation. Our results demonstrate
      that CD72 predominantly down-regulates the major signal transduction pathways
      downstream of the BCR, including NF-AT, NF-kappaB, ERK, JNK, p38-MAPK, and
      PI3K/Akt in mature B cells. CD72 ligation with anti-CD72 Ab (K10.6), which mimics
      the binding of CD100 (a natural ligand for CD72) to release the inhibitory
      function of CD72, augments cell proliferation, Ca(2+) flux, IkappaBalpha
      activation, and ERK MAPK activity upon Ag stimulation in wild-type B cells. In
      addition, we show direct evidence that CD72 promotes cell cycle arrest and
      apoptosis after Ag stimulation in mature B cells. Taken together, our findings
      conclude that CD72 plays a dominant role as a negative regulator of BCR signaling
      in primary mature B lymphocytes.

PMID- 16622000
TI  - Antigen-induced IL-10+ regulatory T cells are independent of CD25+ regulatory
      cells for their growth, differentiation, and function.
AB  - Recent studies have emphasized the importance of T cells with
      regulatory/suppressor properties in controlling autoimmune diseases. A number of
      different types of regulatory T cells have been described with the best
      characterized being the CD25(+) population. In addition, it has been shown that
      regulatory T cells can be induced by specific Ag administration. In this study,
      we investigate the relationship between peptide-induced, CD4(+) regulatory T
      cells and naturally occurring CD4(+)CD25(+) cells derived from the Tg4 TCR
      transgenic mouse. Peptide-induced cells were FoxP3(-) and responded to Ag by
      secreting IL-10, whereas CD25(+) cells failed to secrete this cytokine. Both cell
      types were able to suppress the proliferation of naive lymphocytes in vitro
      although with distinct activation sensitivities. Depletion of CD25(+) cells did
      not affect the suppressive properties of peptide-induced regulators. Furthermore,
      peptide-induced regulatory/suppressor T cells could be generated in RAG(-/-), TCR
      transgenic mice that do not spontaneously generate CD25(+) regulatory cells.
      These results demonstrate that these natural and induced regulatory cells fall
      into distinct subsets.

PMID- 16622001
TI  - Preservation of functional virus-specific memory CD8+ T lymphocytes in
      vaccinated, simian human immunodeficiency virus-infected rhesus monkeys.
AB  - Functional impairment of virus-specific memory CD8(+) T lymphocytes has been
      associated with clinical disease progression following HIV, SIV, and simian human
      immunodeficiency virus infection. These lymphocytes have a reduced capacity to
      produce antiviral cytokines and mediators involved in the lysis of virally
      infected cells. In the present study, we used polychromatic flow cytometry to
      assess the frequency and functional capacity of central memory (CD28(+)CD95(+))
      and effector memory (CD28(-)CD95(+)) subpopulations of Gag-specific CD8(+) T
      cells in SIV/simian human immunodeficiency virus-infected rhesus monkeys. The aim
      of this study was to determine whether Ag-specific, memory CD8(+) T cell function
      could be preserved in infected monkeys that had been immunized before infection
      with a vaccine regimen consisting of a plasmid DNA prime followed by a
      recombinant viral vector boost. We observed that vaccination was associated with
      the preservation of Gag-specific central memory CD8(+) T cells that were
      functionally capable of producing IFN-gamma, and effector memory CD8(+) T cells
      that were capable of producing granzyme B following viral Ag exposure.

PMID- 16622002
TI  - Stimulation of human endothelium with IL-3 induces selective basophil
      accumulation in vitro.
AB  - Basophils have been shown to accumulate in allergic airways and other
      extravascular sites. Mechanisms responsible for the selective recruitment of
      basophils from the blood into tissue sites remain poorly characterized. In this
      study, we characterized human basophil rolling and adhesion on HUVECs under
      physiological shear flow conditions. Interestingly, treatment of endothelial
      cells with the basophil-specific cytokine IL-3 (0.01-10 ng/ml) promoted basophil
      and eosinophil, but not neutrophil, rolling and exclusively promoted basophil
      adhesion. Preincubation of HUVECs with an IL-3R-blocking Ab (CD123) before the
      addition of IL-3 inhibited basophil rolling and adhesion, implicating IL-3R
      activation on endothelial cells. Incubation of basophils with neuraminidase
      completely abolished both rolling and adhesion, indicating the involvement of
      sialylated structures in the process. Abs to the beta(1) integrins, CD49d and
      CD49e, as well as to P-selectin and P-selectin glycoprotein ligand 1, inhibited
      basophil rolling and adhesion. Furthermore, blocking chemokine receptors
      expressed by basophils, such as CCR2, CCR3, and CCR7, demonstrated that CCR7 was
      involved in the observed recruitment of basophils. These data provide novel
      insights into how IL-3, acting directly on endothelium, can cause basophils to
      preferentially interact with blood vessels under physiological flow conditions
      and be selectively recruited to sites of inflammation.

PMID- 16622003
TI  - Murine model of immune-mediated rejection of the acute lymphoblastic leukemia
      70Z/3.
AB  - 70Z/3 is a murine pre-B cell leukemia line derived from BDF(1) mice and has been
      used in the study of signaling pathways in B cells. 70Z/3 cells were initially
      found to cause widespread disease upon injections in animals. We have isolated
      70Z/3 variants divergent in their capacity to lead to morbidity after injections.
      One variant, 70Z/3-NL, elicits an immune response protecting the animal from
      tumor growth. Another variant, 70Z/3-L, does not induce an effective immune
      response and causes morbidity. We demonstrated that both CD4(+) and CD8(+) T
      cells are required for the rejection of 70Z/3-NL cells. Interestingly, the immune
      response generated against 70Z/3-NL cells was found to protect against a
      challenge with the lethal variant, 70Z/3-L. This indicates that although both
      lines can be recognized and killed by the immune system, only 70Z/3-NL is capable
      of inducing a protective response. Further observations, using subclones isolated
      from 70Z/3-NL, demonstrated that immune recognition of a portion of the cells was
      sufficient for protection. Depletion of CD4(+) and CD8(+) T cells in animals
      injected previously with 70Z/3-NL cells showed that T cells, and not Abs, were
      required for the maintenance of the protection initiated by 70Z/3-NL. We tested
      the capacity of 70Z/3-NL cells to treat mice challenged with 70Z/3-L. We can
      delay injections of 70Z/3-NL and still provide protection for the animals. We
      have a model of immune-mediated rejection which will allow us to dissect the
      requirements for the initiation of immune responses against an ALL tumor cell
      line.

PMID- 16622004
TI  - Notch-1 up-regulation and signaling following macrophage activation modulates
      gene expression patterns known to affect antigen-presenting capacity and
      cytotoxic activity.
AB  - Notch signaling has been extensively implicated in cell-fate determination along
      the development of the immune system. However, a role for Notch signaling in
      fully differentiated immune cells has not been clearly defined. We have analyzed
      the expression of Notch protein family members during macrophage activation.
      Resting macrophages express Notch-1, -2, and -4, as well as the Notch ligands
      Jagged-1 and -2. After treatment with LPS and/or IFN-gamma, we observed a p38
      MAPK-dependent increase in Notch-1 and Jagged-1 mRNA and protein levels. To study
      the role of Notch signaling in macrophage activation, we forced the transient
      expression of truncated, active intracellular Notch-1 (Notch-IC) proteins in Raw
      264.7 cells and analyzed their effects on the activity of transcription factors
      involved in macrophage activation. Notch-IC increased STAT-1-dependent
      transcription. Furthermore, Raw 264.7 Notch-IC stable transfectants increased
      STAT1-dependent transcription in response to IFN-gamma, leading to higher
      expression of IFN regulatory factor-1, suppressor of cytokine signaling-1, ICAM
      1, and MHC class II proteins. This effect was independent from an increase of
      STAT1 Tyr or Ser phosphorylation. However, inducible NO synthase expression and
      NO production decreased under the same conditions. Our results show that Notch up
      regulation and subsequent signaling following macrophage activation modulate gene
      expression patterns known to affect the function of mature macrophages.

PMID- 16622005
TI  - Naturally occurring CD4+Foxp3+ regulatory T cells are an essential, IL-10
      independent part of the immunoregulatory network in Schistosoma mansoni egg
      induced inflammation.
AB  - In acute and chronic schistosomiasis, survival of the host requires a carefully
      balanced immune response against highly immunogenic parasite eggs. We
      characterized the phenotype, distribution, and functional role of CD4(+)Foxp3(+)
      naturally occurring regulatory T cells (naTregs) in schistosome egg-induced
      inflammation. In adoptive transfer experiments and by intracellular staining for
      Foxp3, we demonstrate significant frequencies of naTregs in hepatic granulomas
      and draining lymphoid tissues of mice infected with the trematode Schistosoma
      mansoni. Strikingly, egg-induced inflammation does not change the normal ratio
      between naTregs and effector CD4(+) T cells at the inflammatory site or in
      lymphoid organs in acute or chronic disease. However, increasing frequencies of
      CD103-expressing cells in the naTreg compartment indicate a change in phenotype
      for naTregs with disease progression. Because CD103 was described recently as an
      activation marker for naTregs, we speculate that naTregs in chronic
      schistosomiasis are potentially more suppressive. Furthermore, we found that most
      naTregs do not contribute to egg-induced IL-4 and IL-10 production. Importantly,
      depletion of CD25(+) naTregs strongly enhances the frequency of IL-4-producing
      effector T cells in acute egg-induced inflammation. It does not change clonal
      expansion of activated CD4(+) T cells. This regulation of egg-induced cytokine
      production does not require the presence of IL-10. These data demonstrate that
      naTregs limit egg-induced effector-cytokine production in our model. Our results
      identify naTregs as an important, IL-10-independent part of the regulatory
      network in schistosome egg-induced inflammation.

PMID- 16622006
TI  - Cooperation between TNF receptor-associated factors 1 and 2 in CD40 signaling.
AB  - TNFR-associated factor 1 (TRAF1) is unique among the TRAF family, lacking most
      zinc-binding features, and showing marked up-regulation following activation
      signals. However, the biological roles that TRAF1 plays in immune cell signaling
      have been elusive, with many reports assigning contradictory roles to TRAF1. The
      overlapping binding site for TRAFs 1, 2, and 3 on many TNFR superfamily
      molecules, together with the early lethality of mice deficient in TRAFs 2 and 3,
      has complicated the quest for a clear understanding of the functions of TRAF1.
      Using a new method for gene targeting by homologous recombination in somatic
      cells, we produced and studied signaling by CD40 and its viral oncogenic mimic,
      latent membrane protein 1 (LMP1) in mouse B cell lines lacking TRAF1, TRAF2, or
      both TRAFs. Results indicate that TRAFs 1 and 2 cooperate in CD40-mediated
      activation of the B cell lines, with a dual deficiency leading to a markedly
      greater loss of function than that of either TRAF alone. In the absence of TRAF1,
      an increased amount of TRAF2 was recruited to lipid rafts, and subsequently, more
      robust degradation of TRAF2 and TRAF3 was induced in response to CD40 signaling.
      In contrast, LMP1 did not require either TRAFs 1 or 2 to induce activation. Taken
      together, our findings indicate that TRAF1 and TRAF2 cooperate in CD40 but not
      LMP1 signaling and suggest that cellular levels of TRAF1 may play an important
      role in modulating the degradation of TRAF2 and TRAF3 in response to signals from
      the TNFR superfamily.

PMID- 16622007
TI  - Scanning the HIV genome for CD4+ T cell epitopes restricted to HLA-DP4, the most
      prevalent HLA class II molecule.
AB  - HLA-DP4 alleles are carried by 75% of individuals and are the most frequent HLA
      II alleles worldwide. Because we have recently characterized the peptide-binding
      specificity of HLA-DP4 molecules, we developed a peptide-binding prediction
      method to identify HLA-DP4-restricted peptides in multiple Ags. CD4(+) T cell
      response plays a key role in the immune control of HIV infection, but few HIV
      specific T cell epitopes with multi-individual specificity have been identified.
      They are mostly restricted to HLA-DR molecules, which are very polymorphic
      molecules. We therefore looked for HLA-DP4-restricted CD4(+) T cell epitopes in
      the whole genome of HIV. Twenty-one peptides were selected from the HXB2 HIV
      genome based on the prediction of binding to HLA-DP4 molecules. They were
      submitted to HLA-DP4-binding assays. Seventeen peptides bound to the HLA-DP401
      molecule, whereas 15 peptides bound to HLA-DP402. Six peptides bound very tightly
      to HLA-DP401 and were investigated for their capacity to induce specific CD4(+) T
      cell lines in vitro using dendritic cells and CD4(+) T cells collected from eight
      seronegative HLA-DP4(+) donors. Four peptides from env and reverse transcriptase
      proteins induced in vitro-specific T cell lines restricted to HLA-DP4 molecules.
      Peptide-induced T cells recognized variants other than the HXB2 sequence and were
      stimulated by native Ags processed by immature dendritic cells. The reverse
      transcriptase peptide is present in 65% of the isolated HIV variants. To our
      knowledge, we describe the first HIV epitopes restricted to HLA-DP4 molecules.

PMID- 16622008
TI  - Activation of V(D)J recombination at the IgH chain JH locus occurs within a 6
      kilobase chromatin domain and is associated with nucleosomal remodeling.
AB  - IgH genes are assembled during early B cell development by a series of regulated
      DNA recombination reactions in which DH and JH segments are first joined followed
      by V(H) to DJH rearrangement. Recent studies have highlighted the role of
      chromatin structure in the control of V(D)J recombination. In this study, we show
      that, in murine pro-B cell precursors, the JH segments are located within a 6-kb
      DNase I-sensitive chromatin domain containing acetylated histones H3 and H4,
      which is delimited 5' by the DQ52 promoter element and 3' by the intronic
      enhancer. Within this domain, the JH segments are covered by phased nucleosomes.
      High-resolution mapping of nucleosomes reveals that, in pro-B cells, unlike
      recombination refractory nonlymphoid cells, the recombination signal sequences
      flanking the four JH segments are located in regions of enhanced micrococcal
      nuclease and restriction enzyme accessibility, corresponding to either nucleosome
      free regions or DNA rendered accessible within a nucleosome. These results
      support the idea that nucleosome remodeling provides an additional level of
      control in the regulation of Ig locus accessibility to recombination factors in B
      cell precursors.

PMID- 16622009
TI  - Regulation of N-formyl peptide receptor signaling and trafficking by individual
      carboxyl-terminal serine and threonine residues.
AB  - Adaptation, defined as the diminution of receptor signaling in the presence of
      continued or repeated stimulation, is critical to cellular function. G protein
      coupled receptors (GPCRs) undergo multiple adaptive processes, including
      desensitization and internalization, through phosphorylation of cytoplasmic
      serine and threonine residues. However, the relative importance of individual and
      combined serine and threonine residues to these processes is not well understood.
      We examined this mechanism in the context of the N-formyl peptide receptor (FPR),
      a well-characterized member of the chemoattractant/chemokine family of GPCRs
      critical to neutrophil function. To evaluate the contributions of individual and
      combinatorial serine and threonine residues to internalization, desensitization,
      and arrestin2 binding, 30 mutant forms of the FPR, expressed in the human
      promyelocytic U937 cell line, were characterized. We found that residues
      Ser(328), Ser(332), and Ser(338) are individually critical, and indeed
      sufficient, for internalization, desensitization, and arrestin2 binding, but that
      the presence of neighboring threonine residues can inhibit these processes.
      Additionally, we observed no absolute correlation between arrestin binding and
      either internalization or desensitization, suggesting the existence of arrestin
      independent mechanisms for these processes. Our results suggest C-terminal serine
      and threonine residues of the FPR represent a combinatorial code, capable of both
      positively and negatively regulating signaling and trafficking. This study is
      among the first detailed analyses of a complex regulatory site in a GPCR, and
      provides insight into GPCR regulatory mechanisms.

PMID- 16622011
TI  - Triggering of T cell activation via CD4 dimers.
AB  - The onset of activation in Th cells is triggered by localized co-engagement of
      TCRs and the coreceptor CD4. A CD4 crystal suggested that CD4 may form dimers in
      some circumstances. In this study, we use live-cell fluorescence resonance energy
      transfer imaging to demonstrate that CD4 dimers are present at a basal level on
      the cell surface and accumulate at the synapse. Mechanistically, we reveal two
      conditions under which dimers are highly relevant. First, CD4 dimers are more
      proficient in mediating prolonged cell contacts with APCs in the presence or
      absence of Ag. This is consistent with a model whereby the dimer functions to
      increase T-APC avidity. Second, we show that dimer mutations result in an
      increased level of an inactive lckTyr(505) bound to the CD4 molecule relative to
      dimer-competent CD4. We also find a consistent defect in signaling onset in these
      cells. This supports a role for CD4 dimerization in maintaining active signaling
      machinery. We suggest that modulation of the dimer/monomer ratio may permit
      tuning of activation thresholds during initial engagement.

PMID- 16622012
TI  - Replication initiation from a novel origin identified in the Th2 cytokine cluster
      locus requires a distant conserved noncoding sequence.
AB  - Lineage commitment of Th cells is associated with the establishment of specific
      transcriptional programs of cytokines. However, how Th cell differentiation
      affects the program of DNA replication has not been addressed. To gain insight
      into interplays between differentiation-induced transcription regulation and
      initiation of DNA replication, we took advantage of an in vitro differentiation
      system of naive T cells, in which one can manipulate their differentiation into
      Th1 or Th2 cells. We searched for replication origins in the murine IL-4/IL-13
      locus and compared their profiles in the two Th cell lineages which were derived
      in vitro from the same precursor T cells. We identified a replication origin
      (ori(IL-13)) downstream from exon 4 of IL-13 and showed that this origin
      functions in both Th2 and Th1 cells. A distant regulatory element called CNS-1
      (conserved noncoding sequence 1) in the IL-4/IL-13 intergenic region coincides
      with a Th2-specific DNase I-hypersensitive site and is required for efficient,
      coordinated expression of Th2 cytokines. Replication initiation from ori(IL-13)
      is significantly reduced in Th1 and Th2 cells derived from CNS-1-deficient mice.
      However, the replication timing of this locus is consistently early during S
      phase in both Th1 and Th2 cells under either the wild-type or CNS-1 deletion
      background. Thus, the conserved noncoding element in the intergenic region
      regulates replication initiation from a distant replication origin in a manner
      independent from its effect on lineage-specific transcription but not the
      replication timing of the segment surrounding this origin.

PMID- 16622010
TI  - A role for the MutL mismatch repair Mlh3 protein in immunoglobulin class switch
      DNA recombination and somatic hypermutation.
AB  - Class switch DNA recombination (CSR) and somatic hypermutation (SHM) are central
      to the maturation of the Ab response. Both processes involve DNA mismatch repair
      (MMR). MMR proteins are recruited to dU:dG mispairs generated by activation
      induced cytidine deaminase-mediated deamination of dC residues, thereby promoting
      S-S region synapses and introduction of mismatches (mutations). The MutL homolog
      Mlh3 is the last complement of the mammalian set of MMR proteins. It is highly
      conserved in evolution and is essential to meiosis and microsatellite stability.
      We used the recently generated knockout mlh3(-/-) mice to address the role of
      Mlh3 in CSR and SHM. We found that Mlh3 deficiency alters both CSR and SHM. mlh3(
      /-) B cells switched in vitro to IgG and IgA but displayed preferential targeting
      of the RGYW/WRCY (R = A or G, Y = C or T, W = A or T) motif by Sgamma1 and
      Sgamma3 breakpoints and introduced more insertions and fewer donor/acceptor
      microhomologies in Smu-Sgamma1 and Smu-Sgamma3 DNA junctions, as compared with
      mlh3(+/+) B cells. mlh3(-/-) mice showed only a slight decrease in the frequency
      of mutations in the intronic DNA downstream of the rearranged J(H)4 gene.
      However, the residual mutations were altered in spectrum. They comprised a
      decreased proportion of mutations at dA/dT and showed preferential RGYW/WRCY
      targeting by mutations at dC/dG. Thus, the MMR Mlh3 protein plays a role in both
      CSR and SHM.

PMID- 16622013
TI  - The autoimmune diabetes locus Idd9 regulates development of type 1 diabetes by
      affecting the homing of islet-specific T cells.
AB  - Several genetic insulin-dependent diabetes (Idd) intervals that confer resistance
      to autoimmune diabetes have been identified in mice and humans, but the
      mechanisms by which they protect against development of diabetes have not been
      elucidated. To determine the effect of Idd9 on the function of islet-specific T
      cells, we established novel BDC-Idd9 mice that harbor BDC2.5 TCR transgenic T
      cells containing the Idd9 of diabetes-resistant B10 mice. We show that the
      development and functional responses of islet-specific T cells from BDC-Idd9 mice
      are not defective compared with those from BDC mice, which contain the Idd9 of
      diabetes-susceptible NOD mice. Upon transfer, BDC T cells rapidly induced severe
      insulitis and diabetes in NOD.scid mice, whereas those from BDC-Idd9 mice
      mediated a milder insulitis and induced diabetes with a significantly delayed
      onset. BDC and BDC-Idd9 T cells expanded comparably in recipient mice. However,
      BDC-Idd9 T cells accumulated in splenic periarteriolar lymphatic sheaths, whereas
      BDC T cells were mainly found in pancreatic lymph nodes and pancreata of
      recipients, indicating that the transferred T cells differed in their homing. We
      provide evidence that the migration pattern of transferred BDC and BDC-Idd9 T
      cells at least partly depends on their differential chemotaxis toward the CCR7
      ligand CCL19. Taken together, our data show that the Idd9 locus regulates
      development of type 1 diabetes by affecting the homing of islet-specific T cells.

PMID- 16622014
TI  - Enhancement of LFA-1-mediated T cell adhesion by human T lymphotropic virus type
      1 p12I1.
AB  - Cell-to-cell transmission of retroviruses, such as human T lymphotropic virus
      type 1 (HTLV-1), is well documented, but the roles of viral regulatory or other
      nonstructural proteins in the modulation of T cell adhesion are incompletely
      understood. In this study we tested the role of the HTLV-1 accessory protein,
      p12(I), on LFA-1-mediated cell adhesion. p12(I) is critical for early HTLV-1
      infection by causing the release of calcium from the endoplasmic reticulum to
      activate NFAT-mediated transcription. We tested the role of this novel viral
      protein in mediating LFA-1-dependent cell adhesion. Our data indicated that T
      cells expressing a mutant HTLV-1 provirus that does not produce p12(I) mRNA
      (ACH.p12(I)) exhibited reduced LFA-1-mediated adhesion compared with wild-type
      HTLV-1-expressing cells (ACH). Furthermore, the expression of p12(I) in Jurkat T
      cells using lentiviral vectors enhanced LFA-1-mediated cell adhesion, which was
      inhibited by the calcium chelator BAPTA-AM, the calcium channel blocker SK&F
      96365, and calpeptin, an inhibitor of the calcium-dependent protease calpain.
      Similar to the intracellular calcium mobilizer, thapsigargin, the expression of
      p12(I) in Jurkat T cells induced cell surface clustering of LFA-1 without
      changing the level of integrin expression. Our data are the first to indicate
      that HTLV-1 p12(I), in addition to enhancing T cell activation, promotes cell-to
      cell spread by inducing LFA-1 clustering on T cells via calcium-dependent
      signaling.

PMID- 16622015
TI  - TAT-BH4 and TAT-Bcl-xL peptides protect against sepsis-induced lymphocyte
      apoptosis in vivo.
AB  - Apoptosis is a key pathogenic mechanism in sepsis that induces extensive death of
      lymphocytes and dendritic cells, thereby contributing to the immunosuppression
      that characterizes the septic disorder. Numerous animal studies indicate that
      prevention of apoptosis in sepsis improves survival and may represent a potential
      therapy for this highly lethal disorder. Recently, novel cell-penetrating peptide
      constructs such as HIV-1 TAT basic domain and related peptides have been
      developed to deliver bioactive cargoes and peptides into cells. In the present
      study, we investigated the effects of sepsis-induced apoptosis in Bcl-x(L)
      transgenic mice and in wild-type mice treated with an antiapoptotic TAT-Bcl-x(L)
      fusion protein and TAT-BH4 peptide. Lymphocytes from Bcl-x(L) transgenic mice
      were resistant to sepsis-induced apoptosis, and these mice had a approximately 3
      fold improvement in survival. TAT-Bcl-x(L) and TAT-BH4 prevented Escherichia coli
      induced human lymphocyte apoptosis ex vivo and markedly decreased lymphocyte
      apoptosis in an in vivo mouse model of sepsis. In conclusion, TAT-conjugated
      antiapoptotic Bcl-2-like peptides may offer a novel therapy to prevent apoptosis
      in sepsis and improve survival.

PMID- 16622016
TI  - Cmv4, a new locus linked to the NK cell gene complex, controls innate resistance
      to cytomegalovirus in wild-derived mice.
AB  - CMV can cause life-threatening disease in immunodeficient hosts. Experimental
      infection in mice has revealed that the genetically determined natural resistance
      to murine CMV (MCMV) may be mediated either by direct recognition between the NK
      receptor Ly49H and the pathogen-encoded glycoprotein m157 or by epistatic
      interaction between Ly49P and the host MHC H-2D(k). Using stocks of wild-derived
      inbred mice as a source of genetic diversity, we found that PWK/Pas (PWK) mice
      were naturally resistant to MCMV. Depletion of NK cells subverted the resistance.
      Analysis of backcrosses to susceptible BALB/c mice revealed that the phenotype
      was controlled by a major dominant locus effect linked to the NK gene complex.
      Haplotype analysis of 41 polymorphic markers in the Ly49h region suggested that
      PWK mice may share a common ancestral origin with C57BL/6 mice; in the latter,
      MCMV resistance is dependent on Ly49H-m157 interactions. Nevertheless, PWK mice
      retained viral resistance against m157-defective mutant MCMV. These results
      demonstrate the presence of yet another NK cell-dependent viral resistance
      mechanism, named Cmv4, which most likely encodes for a new NK activating
      receptor. Identification of Cmv4 will expand our understanding of the specificity
      of the innate recognition of infection by NK cells.

PMID- 16622017
TI  - Loss of dendritic cell migration and impaired resistance to Leishmania donovani
      infection in mice deficient in CCL19 and CCL21.
AB  - The encounter between APC and T cells is crucial for initiating immune responses
      to infectious microorganisms. In the spleen, interaction between dendritic cells
      (DC) and T cells occurs in the periarteriolar lymphoid sheath (PALS) into which
      DC and T cells migrate from the marginal zone (MZ) along chemokine gradients.
      However, the importance of DC migration from the MZ into the PALS for immune
      responses and host resistance to microbial infection has not yet been elucidated.
      In this study, we report that following Leishmania donovani infection of mice,
      the migration of splenic DC is regulated by the CCR7 ligands CCL19/CCL21. DC in
      plt/plt mutant mice that lack these chemokines are less activated and produce
      less IL-12, compared with those in wild-type mice. Similar findings are seen when
      mice are treated with pertussis toxin, which blocks chemokine signaling in vivo.
      plt/plt mice had increased susceptibility to L. donovani infection compared with
      wild-type mice, as determined by spleen and liver parasite burden. Analysis of
      splenic cytokine profiles at day 14 postinfection demonstrated that IFN-gamma and
      IL-4 mRNA accumulation was comparable in wild-type and plt/plt mice. In contrast,
      accumulation of mRNA for IL-10 was elevated in plt/plt mice. In addition, plt/plt
      mice mounted a delayed hepatic granulomatous response and fewer effector T cells
      migrated into the liver. Taken together, we conclude that DC migration from the
      MZ to the PALS is necessary for full activation of DC and the optimal induction
      of protective immunity against L. donovani.

PMID- 16622018
TI  - Macrophage's proinflammatory response to a mycobacterial infection is dependent
      on sphingosine kinase-mediated activation of phosphatidylinositol phospholipase
      C, protein kinase C, ERK1/2, and phosphatidylinositol 3-kinase.
AB  - Previous studies have shown that the ability of Mycobacterium tuberculosis to
      block a Ca(2+) flux is an important step in its capacity to halt phagosome
      maturation. This affect on Ca(2+) release results from M. tuberculosis inhibition
      of sphingosine kinase (SPK) activity. However, these studies did not address the
      potential role of SPK and Ca(2+) in other aspects of macrophage activation
      including production of proinflammatory mediators. We previously showed that
      nonpathogenic Mycobacterium smegmatis and to a lesser extent pathogenic
      Mycobacterium avium, activate Ca(2+)-dependent calmodulin/calmodulin kinase and
      MAPK pathways in murine macrophages leading to TNF-alpha production. However,
      whether SPK functions in promoting MAPK activation upon mycobacterial infection
      was not defined in these studies. In the present work we found that SPK is
      required for ERK1/2 activation in murine macrophages infected with either M.
      avium or M. smegmatis. Phosphoinositide-specific phospholipase C (PI-PLC) and
      conventional protein kinase C (cPKC) were also important for ERK1/2 activation.
      Moreover, there was increased activation of cPKC and PI3K in macrophages infected
      with M. smegmatis compared with M. avium. This cPKC and PI3K activation was
      dependent on SPK and PI-PLC. Finally, in macrophages infected with M. smegmatis
      compared with M. avium, we observed enhanced secretion of TNF-alpha, IL-6,
      RANTES, and G-CSF and found production of these inflammatory mediators to be
      dependent on SPK, PI-PLC, cPKC, and PI3K. These studies are the first to show
      that the macrophage proinflammatory response following a mycobacterial infection
      is regulated by SPK/PI-PLC/PKC activation of ERK1/2 and PI3K pathways.

PMID- 16622019
TI  - CD4 T cells from malaria-nonexposed individuals respond to the CD36-Binding
      Domain of Plasmodium falciparum erythrocyte membrane protein-1 via an MHC class
      II-TCR-independent pathway.
AB  - We have studied the human CD4 T cell response to a functionally conserved domain
      of Plasmodium falciparum erythrocyte membrane protein-1, cysteine interdomain
      region-1alpha (CIDR-1alpha). Responses to CIDR-1alpha were striking in that both
      exposed and nonexposed donors responded. The IFN-gamma response to CIDR-1alpha in
      the nonexposed donors was partially independent of TCR engagement of MHC class II
      and peptide. Contrastingly, CD4 T cell and IFN-gamma responses in malaria-exposed
      donors were MHC class II restricted, suggesting that the CD4 T cell response to
      CIDR-1alpha in malaria semi-immune adults also has a TCR-mediated component,
      which may represent a memory response. Dendritic cells isolated from human
      peripheral blood were activated by CIDR-1alpha to produce IL-12, IL-10, and IL
      18. IL-12 was detectable only between 6 and 12 h of culture, whereas the IL-10
      continued to increase throughout the 24-h time course. These data strengthen
      previous observations that P. falciparum interacts directly with human dendritic
      cells, and suggests that the interaction between CIDR-1alpha and the host cell
      may be responsible for regulation of the CD4 T cell and cytokine responses to P.
      falciparum-infected erythrocytes reported previously.

PMID- 16622020
TI  - Expression of functionally different dectin-1 isoforms by murine macrophages.
AB  - Dectin-1 is a specific receptor for beta-glucans and a major receptor for fungal
      particles on macrophages (Mphi). It is a type II membrane receptor that has a C
      terminal, NK-like, C-type lectin-like domain separated from the cell membrane by
      a short stalk region and a cytoplasmic immunoreceptor tyrosine-based activation
      like motif. We observed functional differences in dectin-1-dependent recognition
      of fungal particles by Mphi from different mouse strains. RT-PCR analysis
      revealed that mice have at least two splice forms of dectin-1, generated by
      differential usage of exon 3, encoding the full-length dectin-1A and a stalkless
      Mphi dectin-1B. Mphi from BALB/c mice and genetically related mice expressed both
      isoforms in similar amounts, whereas Mphi from C57BL/6 and related mice mainly
      expressed the smaller isoform. NIH-3T3 fibroblast and RAW264.7 macrophage cell
      lines stably expressing either isoform were able to bind and phagocytose zymosan
      at 37 degrees C. However, binding by the smaller dectin-1B isoform was
      significantly affected at lower temperatures. These properties were shared by the
      equivalent human isoforms. The relative ability of each of the isoforms to induce
      TNF-alpha production in RAW264.7 Mphi was also found to be different. These
      results are the first evidence that dectin-1 isoforms are functionally distinct
      and indicate that differential isoform usage may represent a mechanism of
      regulating cellular responses to beta-glucans.

PMID- 16622021
TI  - Reduced nitric oxide synthase 2 (NOS2) promoter activity in the Syrian hamster
      renders the animal functionally deficient in NOS2 activity and unable to control
      an intracellular pathogen.
AB  - Progressive disease in the hamster model of visceral leishmaniasis, caused by
      Leishmania donovani, in contrast to infection in mice, mimics the progressive
      disease observed in untreated humans. During progressive infection in hamsters,
      there was a vigorous type 1 cellular immune response, which is typically
      associated with control of infection, suggesting that there was ineffective IFN
      gamma-mediated macrophage activation. Indeed, at the site of infection, hamsters
      did not express NO synthase 2 (NOS2), which is the primary mechanism for control
      of infection in mice. Furthermore, in striking contrast to mouse macrophages, IFN
      gamma-activated hamster macrophages did not did not express NOS2 nor generate NO,
      and were unable to restrict the replication of intracellular L. donovani. The
      absent hamster NOS2 expression was not the result of NOS2 gene deletion and the
      NOS2 cDNA had an intact open reading frame. Furthermore, the impaired
      transcription of NOS2 mRNA was selective and not due to global impairment of IFN
      gamma signaling (members of the IFN-gamma-signaling pathway were expressed and
      functional and IFN-gamma up-regulated several primary and secondary response
      genes). Strikingly, the proximal hamster NOS2 promoter, like the human ortholog,
      had >20-fold less basal and IFN-gamma/LPS-inducible activity than the
      corresponding mouse promoter. Thus, reduced basal and IFN-gamma-induced activity
      of the hamster NOS2 transcriptional unit, which is unique to this small animal
      and similar to the human counterpart, accompanies the inability of the animal to
      control an intracellular pathogen.

PMID- 16622022
TI  - Respiratory syncytial virus inhibits granulocyte apoptosis through a
      phosphatidylinositol 3-kinase and NF-kappaB-dependent mechanism.
AB  - Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract
      disease in children. It is associated with increased neutrophil numbers in the
      airway. In this study, we assessed whether this ssRNA virus can directly
      influence granulocyte longevity. By culturing RSV with granulocytes, it was
      observed that virus delays both constitutive neutrophil and eosinophil apoptosis.
      Using pharmacological inhibitors, the RSV-induced delay in neutrophil apoptosis
      was found to be dependent on both PI3K and NF-kappaB, but not p38 MAPK or
      MEK1/MEK2 activation. Using blocking Abs and a reporter cell line, we were able
      to exclude TLR4 as the receptor responsible for mediating RSV-induced delay in
      neutrophil apoptosis. The antiapoptotic effect was abrogated by preincubation
      with the lysosomotropic agent chloroquine, indicating the requirement for
      endolysosomal internalization. Furthermore, addition of ssRNA, a ligand for the
      intracellular TLR7/TLR8, also inhibited neutrophil apoptosis, suggesting that
      intracellular TLRs could be involved in induction of the antiapoptotic effect.
      Using the BioPlex cytokine detection assay (Bio-Rad), we found that IL-6 was
      present in supernatants from RSV-exposed neutrophils. IL-6 was found to inhibit
      neutrophil apoptosis, suggesting that there is an autocrine or paracrine
      antiapoptotic role for IL-6. Finally, RSV treatment of neutrophils resulted in
      increased expression of the antiapoptotic Bcl-2 protein Mcl-1. Taken together,
      our findings suggest involvement of multiple intracellular mechanisms responsible
      for RSV-induced survival of granulocytes and point toward a role for
      intracellular TLRs in mediating these effects.

PMID- 16622023
TI  - Differential requirements of T cell subsets for CD40 costimulation in immunity to
      Blastomyces dermatitidis.
AB  - Cell-mediated immunity and production of type 1 cytokines are the main defenses
      against pathogenic fungi. Ligation of CD40 by CD40L on T cells is critical for
      the induction of these immune responses in vivo. We explored the role of
      CD40/CD40L interactions in vaccine immunity to Blastomyces dermatitidis by
      immunizing CD40(-/-) and CD40L(-/-) mice and analyzing their resistance to
      reinfection in a murine pulmonary model. In the absence of CD40 or CD40L, CD4(+)
      cells failed to get primed or produce type 1 cytokine and impaired the generation
      of CD8(+) T1 cells. The CD8(+) T cell defect was not due to regulatory T cells or
      impaired APC maturation or Ag presentation to T cells. If CD4(+) cells were first
      eliminated, vaccination of CD40(-/-) and CD40L(-/-) mice restored priming of
      CD8(+) cells, type 1 cytokine production, and resistance. Hence, CD4(+) and
      CD8(+) cells differ sharply in their requirement for CD40/CD40L interaction
      during the generation of antifungal immunity. Despite the plasticity of T cell
      subsets in vaccine immunity, in absence of CD40/CD40L interaction, CD4(+) cells
      may impede the priming of CD8(+) cells at the cost of host survival against a
      lethal infectious disease.

PMID- 16622024
TI  - A critical role for adrenomedullin-calcitonin receptor-like receptor in
      regulating rheumatoid fibroblast-like synoviocyte apoptosis.
AB  - Rheumatoid arthritis (RA) is characterized by fibroblast-like synoviocyte (FLS)
      hyperplasia, which is partly ascribable to decreased apoptosis. In this study, we
      show that adrenomedullin (ADM), an antiapoptotic peptide, is constitutively
      secreted in larger amounts by FLS from joints with RA (RA-FLS) than with
      osteoarthritis (OA-FLS). ADM secretion was regulated by TNF-alpha.
      Peptidylglycine alpha-amidating monooxygenase, the ADM-processing enzyme, was
      expressed at the mRNA level by both RA-FLS and OA-FLS. Constituents of the ADM
      heterodimeric receptor calcitonin receptor-like receptor (CRLR)/receptor activity
      modifying protein (RAMP)-2 were up-regulated at the mRNA and protein levels in
      cultured RA-FLS compared with OA-FLS. ADM induced rapid intracellular cAMP
      production in FLS and reduced caspase-3 activity, DNA fragmentation, and
      chromatin condensation in RA-FLS exposed to apoptotic conditions, indicating that
      CRLR/RAMP-2 was fully functional. ADM-induced cAMP production was less marked in
      OA-FLS than in RA-FLS, suggesting differences in receptor regulation and
      expression. ADM dose-dependently inhibited RA-FLS apoptosis, and this effect was
      reversed by the 22-52 ADM antagonist peptide. ADM inhibited RA-FLS apoptosis
      triggered by extrinsic and intrinsic pathways. Our data suggest that ADM may
      prevent or reduce RA-FLS apoptosis, via up-regulation of its functional receptor
      CRLR/RAMP-2. Regulation of ADM secretion and/or CRLR/RAMP-2 activation may
      constitute new treatment strategies for RA.

PMID- 16622025
TI  - IL-1beta-specific up-regulation of neutrophil gelatinase-associated lipocalin is
      controlled by IkappaB-zeta.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is a siderophore-binding
      protein that exerts a bacteriostatic effect by sequestering iron. Strong
      induction of NGAL synthesis has been observed in inflamed epithelium of the lungs
      and colon. Expression of NGAL is up-regulated in the lung epithelial cell line
      A549 by IL-1beta, but not by TNF-alpha, despite an induction of NF-kappaB binding
      to the NGAL promoter by both cytokines. In this study, we present evidence that
      the IL-1beta specificity is caused by a requirement of the NGAL promoter for the
      NF-kappaB-binding cofactor IkappaB-zeta for transcriptional activation. Up
      regulation of NGAL expression in A549 cells following IL-1beta stimulation was
      dependent on de novo protein synthesis and was greatly diminished by a small
      interfering against IkappaB-zeta mRNA. Cotransfection of A549 cells with a
      plasmid expressing IkappaB-zeta made TNF-alpha capable of inducing NGAL
      transcription, indicating that IkappaB-zeta induction is the only factor
      discriminating between IL-1beta and TNF-alpha in their ability to induce NGAL
      expression. Coexpression of the cofactor Bcl-3, which is closely related to
      IkappaB-zeta, did not enable TNF-alpha to induce NGAL transcription. A functional
      NF-kappaB site of the NGAL promoter was required for IkappaB-zeta to exert its
      effect. The human beta defensin 2 gene also required IkappaB-zeta for its IL
      1beta-specific induction in A549 cells. Our findings indicate that a common
      regulatory mechanism has evolved to control expression of a subset of
      antimicrobial proteins expressed in epithelial cells.

PMID- 16622026
TI  - Monocyte and macrophage activation by lipoteichoic Acid is independent of alanine
      and is potentiated by hemoglobin.
AB  - Lipoteichoic acids (LTAs) are Gram-positive bacterial cell wall components that
      elicit mononuclear cell cytokine secretion. Cytokine-stimulating activity is
      thought to be dependent on retaining a high level of ester-linked D-alanine
      residues along the polyglycerol phosphate backbone. However, Streptococcus
      pyogenes LTA essentially devoid of D-alanine caused human and mouse cells to
      secrete as much IL-6 as LTA with a much higher D-alanine content. Furthermore,
      hemoglobin (Hb) markedly potentiates the stimulatory effect of various LTAs on
      mouse macrophages or human blood cells, regardless of their d-alanine content.
      LTA and Hb appear to form a molecular complex, based on the ability of each to
      affect the other's migration on native acrylamide gels, their comigration on
      these gels, and the ability of LTA to alter the absorption spectra of Hb. Because
      S. pyogenes is known to release LTA and secrete at least two potent hemolytic
      toxins, LTA-Hb interactions could occur during streptococcal infections and might
      result in a profound alteration of the local inflammatory response.

PMID- 16622027
TI  - Angiotensin II-induced mononuclear leukocyte interactions with arteriolar and
      venular endothelium are mediated by the release of different CC chemokines.
AB  - Angiotensin II (Ang-II) is associated with atherogenesis and arterial
      subendothelial mononuclear leukocyte infiltration. We have demonstrated that Ang
      II causes the initial attachment of mononuclear cells to the arteriolar
      endothelium. We now report on the contribution of CC chemokines to this response.
      Intraperitoneal administration of 1 nM Ang-II induced MCP-1, RANTES, and MIP
      1alpha generation, maximal at 4 h, followed by mononuclear leukocyte recruitment
      at 8 and 24 h. Using intravital microscopy within the rat mesenteric
      microcirculation 4 h after exposure to 1 nM Ang-II, arteriolar mononuclear cell
      adhesion was 80-90% inhibited by pretreatment with Met-RANTES, a CCR1 and CCR5
      antagonist, or an anti-MCP-1 antiserum, without affecting the increased
      endothelial expression of P-selectin and VCAM-1. Conversely, leukocyte
      interactions with the venular endothelium, although inhibited by Met-RANTES, were
      little affected by the anti-MCP-1. Using rat whole blood in vitro, Ang-II (100
      nM) induced the expression of monocyte CD11b that was inhibited by Met-RANTES but
      not by anti-MCP-1. Stimulation of human endothelial cells (human umbilical
      arterial endothelial cells and HUVECs) with 1-1000 nM Ang-II, predominantly
      acting at its AT(1) receptor, induced the release of MCP-1 within 1 h, RANTES
      within 4 h, and MCP-3 within 24 h. Eotaxin-3, a natural CCR2 antagonist, was
      released within 1 h and may delay mononuclear cell responses to MCP-1. Therefore,
      Ang-II-induced mononuclear leukocyte recruitment at arterioles and venules is
      mediated by the production of different CC chemokines. Thus, Ang-II may be a key
      molecule in the initial attachment of mononuclear cells to the arterial
      endothelium in cardiovascular disease states where this event is a characteristic
      feature.

PMID- 16622028
TI  - Nitrotyrosine proteome survey in asthma identifies oxidative mechanism of
      catalase inactivation.
AB  - Reactive oxygen species and reactive nitrogen species produced by epithelial and
      inflammatory cells are key mediators of the chronic airway inflammation of
      asthma. Detection of 3-nitrotyrosine in the asthmatic lung confirms the presence
      of increased reactive oxygen and nitrogen species, but the lack of identification
      of modified proteins has hindered an understanding of the potential mechanistic
      contributions of nitration/oxidation to airway inflammation. In this study, we
      applied a proteomic approach, using nitrotyrosine as a marker, to evaluate the
      oxidation of proteins in the allergen-induced murine model of asthma. Over 30
      different proteins were targets of nitration following allergen challenge,
      including the antioxidant enzyme catalase. Oxidative modification and loss of
      catalase enzyme function were seen in this model. Subsequent investigation of
      human bronchoalveolar lavage fluid revealed that catalase activity was reduced in
      asthma by up to 50% relative to healthy controls. Analysis of catalase isolated
      from asthmatic airway epithelial cells revealed increased amounts of several
      protein oxidation markers, including chloro- and nitrotyrosine, linking oxidative
      modification to the reduced activity in vivo. Parallel in vitro studies using
      reactive chlorinating species revealed that catalase inactivation is accompanied
      by the oxidation of a specific cysteine (Cys(377)). Taken together, these studies
      provide evidence of multiple ongoing and profound oxidative reactions in
      asthmatic airways, with one early downstream consequence being catalase
      inactivation. Loss of catalase activity likely amplifies oxidative stress,
      contributing to the chronic inflammatory state of the asthmatic airway.

PMID- 16622029
TI  - Absence of IL-1 receptor antagonist impaired wound healing along with aberrant NF
      kappaB activation and a reciprocal suppression of TGF-beta signal pathway.
AB  - Although enhanced expression of IL-1 family proteins, including IL-1alpha, IL
      1beta, and IL-1 receptor antagonist (IL-1ra) during wound healing has been
      observed, the pathophysiological roles of these factors, particularly IL-1ra,
      still remain elusive. We explored skin wound-healing processes in IL-1ra
      deficient mice. Compared to wild-type (WT) mice, IL-1ra-deficient mice exhibited
      impaired wound healing, as evidenced by attenuated collagen deposition and
      delayed neovascularization. In contrast, neutrophil recruitment was significantly
      exaggerated, with the augmented expression of IL-1s, TNF-alpha, and CXC
      chemokines, MIP-2 and KC, in IL-1ra-deficient mice compared with WT mice. Because
      the transcription of these proinflammatory cytokines and CXC chemokines requires
      the activation of NF-kappaB, a major target of IL-1- and TNF-alpha-mediated
      signal pathway, we examined the activation states of NF-kappaB. Nuclear
      translocation of NF-kappaB p65 was significantly enhanced and prolonged in IL-1ra
      deficient mice, compared to that in WT mice. The cross-talk between NF-kappaB and
      TGF-beta-mediated signals has been proposed based on in vitro observations.
      Indeed, compared to WT mice, the amounts of total and phosphorylated Smad2 and
      Smad3 were decreased with a reciprocal increase in the amount of Smad7 in skin
      wound sites of IL-1ra-deficient mice. Moreover, the gene expression of vascular
      endothelial growth factor, a target gene of TGF-beta1, was decreased in IL-1ra
      deficient mice. Thus, the absence of IL-1ra may suppress TGF-beta-mediated
      signaling pathway, which is crucial for collagen deposition and vascular
      endothelial growth factor-mediated neovascularization in wound healing.

PMID- 16622030
TI  - Mast cell-mediated remodeling and fibrinolytic activity protect against fatal
      glomerulonephritis.
AB  - Mast cells are detrimental in several inflammatory diseases; however, their
      physiological roles are also increasingly recognized. Recent data suggest that
      mast cells may also be involved in renal diseases. We therefore used congenitally
      mast cell-deficient W/W(v) mice and normal +/+ littermates to assess their role
      in anti-glomerular basement membrane-induced glomerulonephritis. Following
      administration of anti-glomerular basement membrane Abs, W/W(v) mice exhibited
      increased mortality as compared with +/+ mice owing to rapid deterioration of
      renal function. Reconstitution of the mast cell population in W/W(v) mice
      restored protection. This was independent of activating FcgammaR, as protection
      was also obtained using mast cells deficient in FcRgamma. Comparative
      histological analysis of kidneys showed that deterioration of renal function was
      caused by the presence of thick layers of subendothelial glomerular deposits in
      W/W(v) mice, while +/+ mice or mast cell-reconstituted W/W(v) mice showed
      significantly less. Deposits appeared during the early phase of disease and
      persisted thereafter, and were accompanied by enhanced macrophage recruitment.
      Immunohistochemical analysis revealed increased amounts of fibrin and type I
      collagen in W/W(v) mice, which were also unable to maintain high tissue
      plasminogen activator and urinary-type plasminogen activator activity in urine in
      the heterologous phase of disease. Our results indicate that mast cells by their
      ability to mediate remodeling and repair functions are protective in immune
      complex-mediated glomerulonephritis.

PMID- 16622032
TI  - Lactobacilli-expressed single-chain variable fragment (scFv) specific for
      intercellular adhesion molecule 1 (ICAM-1) blocks cell-associated HIV-1
      transmission across a cervical epithelial monolayer.
AB  - The vaginal and cervical epithelia provide an initial barrier to sexually
      acquired HIV-1 infection in women. To study the interactions between HIV-1
      infected cells or cell-free HIV-1 and the reproductive epithelium, the
      transmission of HIV-1 by infected cells or cell-free virus across human cervical
      epithelial cells was examined using a Transwell culture system. Cell-associated
      HIV-1 was transmitted more efficiently than cell-free virus, and monocyte
      associated virus was transmitted most efficiently. Abs to ICAM-1 added to the
      apical side of the epithelium blocked cell-mediated transepithelial HIV-1
      transmission in vitro. When used in a previously described model of vaginal HIV-1
      transmission in human PBL-SCID mice, anti-murine ICAM-1 Abs (0.4 microg/10
      microl) also blocked vaginal transmission of cell-associated HIV-1 in vivo. To
      evaluate a candidate delivery system for the use of this Ab as an anti-HIV-1
      microbicide, anti-ICAM single-chain variable fragment Abs secreted by transformed
      lactobacilli were evaluated for their protective efficacy in the Transwell model.
      Like the intact Ab and Fab derived from it, the single-chain variable fragment at
      a concentration of 6.7 microg/100 microl was able to reduce HIV-1 transmission by
      70 +/- 5%. These data support the potential efficacy of an anti-ICAM Ab delivered
      by lactobacilli for use as an anti-HIV-1 microbicide.

PMID- 16622031
TI  - Adenosine A2A receptor inactivation increases survival in polymicrobial sepsis.
AB  - The mechanisms governing the impairment of bacterial clearance and immune
      function in sepsis are not known. Adenosine levels are elevated during tissue
      hypoxia and damage associated with sepsis. Adenosine has strong immunosuppressive
      effects, many of which are mediated by A(2A) receptors (A(2A)R) expressed on
      immune cells. We examined whether A(2A)R are involved in the regulation of immune
      function in cecal ligation and puncture-induced murine polymicrobial sepsis by
      genetically or pharmacologically inactivating A(2A)R. A(2A)R knockout (KO) mice
      were protected from the lethal effect of sepsis and had improved bacterial
      clearance compared with wild-type animals. cDNA microarray analysis and flow
      cytometry revealed increased MHC II expression in A(2A)-inactivated mice,
      suggesting improved Ag presentation as a mechanism of protection. Apoptosis was
      attenuated in the spleen of A(2A) KO mice indicating preserved lymphocyte
      function. Levels of the immunosuppressive cytokines IL-10 and IL-6 were markedly
      lower following A(2A)R blockade. Similar to observations with A(2A)R KO mice, an
      A(2A)R antagonist increased survival even when administered in a delayed fashion.
      These studies demonstrate that A(2A)R blockade may be useful in the treatment of
      infection and sepsis.

PMID- 16622033
TI  - Tumor-derived TGFbeta-1 induces dendritic cell apoptosis in the sentinel lymph
      node.
AB  - Lymphatic flux from a primary tumor initially flows into a tumor-draining lymph
      node (LN), the so-called sentinel LN (SLN). Carried by the lymph fluid are a
      variety of mediators produced by the tumor that can influence immune responses
      within the SLN, making it a good model with which to investigate tumor-related
      immunology. For instance, dendritic cell (DC) numbers are reduced in SLNs from
      melanoma and breast cancer patients. In the present study, we investigated the
      mechanism by which DC numbers were reduced within SLNs from patients with non
      small cell lung cancer. We found that the incidence of apoptosis among DCs was
      higher in SLNs than in non-SLNs, as were levels of TGFbeta-1. In contrast, levels
      of TGFbeta-1 mRNA did not differ between SLNs and non-SLNs, but were 30 times
      higher in tumors than in either LN type. In vitro, incubation for 2 days with
      TGFbeta-1 induced apoptosis among both cultured DCs and DCs acutely isolated from
      normal thoracic LNs, effects that were blocked by the TGFbeta-1 inhibitor DAN/Fc
      chimera. Taken together, these results suggest that tumor-derived TGFbeta-1
      induces immunosuppression within SLNs before the movement of tumor cells into the
      SLNs, thereby facilitating metastasis within those nodes.

PMID- 16622034
TI  - Differential restoration of myeloid and plasmacytoid dendritic cells in HIV-1
      infected children after treatment with highly active antiretroviral therapy.
AB  - Numerical and functional deficits in myeloid (mDC) and plasmacytoid dendritic
      cell (pDC) subsets have been found in both adult and pediatric HIV-1 carriers.
      Whether these impaired DC subsets can be restored after treatment with highly
      active antiretroviral therapy (HAART) is currently unknown, especially in HIV-1
      infected children. In this report, we characterized mDC and pDC subsets in 18 HIV
      1-infected children who received HAART treatment and compared them with those in
      6 untreated HIV-1-infected children and 27 HIV-1-uninfected healthy children.
      Among children treated with HAART, 11 were found to suppress HIV-1 replication
      successfully below the detection limit (HAART-suppressed group) while the
      remaining 7 failed (HAART-failure group). In HAART-suppressed children, a gradual
      and complete restoration of the frequency and function of mDCs was observed while
      the recovery of pDCs was only partial. However, mDC and pDC subsets in HARRT
      failure children were indistinguishable from the HAART-naive infected children.
      We also found that mDC frequency and IFN-alpha-releasing capacity of pDC
      positively correlated with CD4 T cell percentages in all HIV-1-infected children.
      In HAART-naive children, the mDC frequency correlated the HIV-1-specific CTL
      frequency. Our findings suggest that HAART has a differential impact on the
      restoration of mDC and pDC subsets. These findings may help guide the development
      of HIV-1-specific immune therapy aimed at fully restoring host immune function in
      chronically HIV-1-infected children.

PMID- 16622035
TI  - STAT3 and NF-kappaB signal pathway is required for IL-23-mediated IL-17
      production in spontaneous arthritis animal model IL-1 receptor antagonist
      deficient mice.
AB  - IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit
      of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from
      activated CD4(+) T cells and stimulating the proliferation of memory CD4(+) T
      cells. We investigated the pathogenic role of IL-23 in CD4(+) T cells in mice
      lacking the IL-1R antagonist (IL-1Ra(-/-)), an animal model of spontaneous
      arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra(-/-)
      mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly
      accelerated this joint inflammation and joint destruction. IL-1beta further
      increased the production of IL-23, which induced IL-17 production and OX40
      expression in splenic CD4(+) T cells of IL-1Ra(-/-) mice. Blocking IL-23 with
      anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte
      cultures. The process of IL-23-induced IL-17 production in CD4(+) T cells was
      mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-kappaB, whereas p38
      MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is
      a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory
      cytokine in the pathogenesis of this IL-1Ra(-/-) model of spontaneous arthritis.
      Its intracellular signaling pathway could be useful therapeutic targets in the
      treatment of autoimmune arthritis.

PMID- 16622036
TI  - Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell
      clones from rheumatic heart disease.
AB  - Molecular mimicry between Streptococcus pyogenes Ags and human proteins has been
      considered as a mechanism leading to autoimmune reactions in rheumatic fever and
      rheumatic heart disease (RHD). Cardiac myosin has been shown as a putative
      autoantigen recognized by autoantibodies of rheumatic fever patients. We assessed
      the human heart-intralesional T cell response against human light meromyosin
      (LMM) and streptococcal M5 peptides and mitral-valve-derived proteins by
      proliferation assay. Cytokines induced by LMM peptides were also evaluated. The
      frequency of intralesional T cell clones that recognized LMM peptides was 63.2%.
      Thirty-four percent of T cell clones presented cross-reactivity with different
      patterns: 1) myosin and valve-derived proteins; 2) myosin and streptococcal M5
      peptides; and 3) myosin, valve-derived proteins and M5 peptides. In addition,
      several LMM peptides were recognized simultaneously showing a multiple reactivity
      pattern of heart-infiltrating T cells. Inflammatory cytokines (IFN-gamma and TNF
      alpha) were predominantly produced by heart-infiltrating T cells upon stimulation
      with LMM peptides. The alignment of LMM and streptococcal M5 peptides showed
      frequent homology among conserved amino acid substitutions. This is the first
      study showing the cellular response by human heart-infiltrating T cells against
      cardiac myosin epitopes in RHD patients. The high percentage of reactivity
      against cardiac myosin strengthens its role as one of the major autoantigens
      involved in rheumatic heart lesions. T cell reactivity toward myosin epitopes in
      RHD patients may also trigger the broad recognition of valvular proteins with
      structural or functional similarities.

PMID- 16622037
TI  - Neonatal immunization with a Sindbis virus-DNA measles vaccine induces adult-like
      neutralizing antibodies and cell-mediated immunity in the presence of maternal
      antibodies.
AB  - Infants younger than age 9 mo do not respond reliably to the live attenuated
      measles vaccine due the immaturity of their immune system and the presence of
      maternal Abs that interfere with successful immunization. We evaluated the immune
      responses elicited by Sindbis virus replicon-based DNA vaccines encoding measles
      virus (MV) hemagglutinin (H, pMSIN-H) or both hemagglutinin and fusion (F, pMSINH
      FdU) glycoproteins in neonatal mice born to naive and measles-immune mothers.
      Despite the presence of high levels of maternal Abs, neonatal immunization with
      pMSIN-H induced long-lasting, high-avidity MV plaque reduction neutralization
      (PRN) Abs, mainly IgG2a, that also inhibited syncytium formation in CD150(+) B95
      8 cells. IgG secreting plasma cells were detected in spleen and bone marrow.
      Newborns vaccinated with pMSINH-FdU elicited PRN titers that surpassed the
      protective level (200 mIU/ml) but were short-lived, had low syncytium inhibition
      capacity, and lacked avidity maturation. This vaccine failed to induce
      significant PRN titers in the presence of placentally transferred Abs. Both pMSIN
      H and pMSINH-FdU elicited strong Th1 type cell-mediated immunity, measured by T
      cell proliferation and IFN-gamma production, that was unaffected by maternal Abs.
      Newborns responded to measles DNA vaccines with similar or even higher PRN titers
      and cell-mediated immunity than adult mice. This study is the first demonstration
      that a Sindbis virus-based measles DNA vaccine can elicit robust MV immunity in
      neonates bypassing maternal Abs. Such a vaccine could be followed by the current
      live attenuated MV vaccine in a heterologous prime-boost to protect against
      measles early in life.

PMID- 16622038
TI  - Differential regulation of mesolimbic alpha 3/alpha 6 beta 2 and alpha 4 beta 2
      nicotinic acetylcholine receptor sites and function after long-term oral nicotine
      to monkeys.
AB  - Because the mesolimbic dopamine system plays a critical role in nicotine
      addiction/reinforcement and because nicotinic receptors regulate dopamine
      release, we initiated a study to evaluate the long-term effects of nicotine (>6
      months at the final dose) on nicotinic acetylcholine receptor (nAChR) sites and
      function in the nucleus accumbens of nonhuman primates. Nicotine was given in the
      drinking water as this mode of administration is long-term but intermittent, thus
      resembling smoking in this aspect. We determined the effects of nicotine
      treatment on function and binding of the alpha3/alpha6beta2* and alpha4beta2*
      nAChRs subtypes in nucleus accumbens, a region directly implicated in the
      addictive effects of nicotine. To evaluate function, we measured nicotine and K+
      evoked [3H]dopamine release from nucleus accumbens synaptosomes. Changes in
      alpha4beta2* and alpha3/alpha6beta2* nAChRs were measured using 125I-epibatidine,
      [125I]A85380 [5-[125I]iodo-3(2(S)-azetidinylmethoxy) pyridine] and 125I-alpha
      conotoxin MII autoradiography. Chronic nicotine treatment, which led to plasma
      nicotine levels in the range of smokers, significantly increased nucleus
      accumbens alpha4beta2* nAChR sites and function compared with control. By
      contrast, this treatment did not significantly change alpha3/alpha6beta2* nAChR
      sites or evoked dopamine release in this region compared with control. Thus,
      these data are distinct from previous results in striatum in which the same
      nicotine treatment paradigm decreased striatal alpha3/alpha6beta2* nAChR sites
      and function. The finding that long-term nicotine treatment selectively modulates
      alpha4beta2* and not alpha3/alpha6beta2* nAChR expression in primate nucleus
      accumbens is consistent with the results of studies in nicotinic receptor mutant
      mice implicating the alpha4beta2* nAChR subtype in nicotine-mediated addiction.

PMID- 16622039
TI  - Nitroglycerin attenuates human endothelial progenitor cell differentiation,
      function, and survival.
AB  - Endothelial progenitor cells (EPCs) participate in angiogenesis and the response
      to chronic ischemia. Risk factors and cardiovascular disease attenuate EPC
      number, function, and survival. Continuous therapy with nitroglycerin (glyceryl
      trinitrate; GTN) is associated with increased vascular oxidative stress, leading
      to nitrate tolerance and endothelial dysfunction. Thus, GTN therapy may also
      affect EPCs. The purpose of this study was to determine whether continuous
      exposure to GTN in vivo or during ex vivo expansion affects the circulating
      number and functional characteristics of human EPCs. To determine the effects of
      continuous in vivo GTN exposure, EPCs isolated from 28 healthy males before and
      after receiving 0.6 mg/h GTN (n=17) or no treatment (n=11) for 1 week were
      expanded for 6 days and compared. To determine the effects of continuous ex vivo
      GTN exposure, EPCs isolated before randomization were expanded for 6 days in
      medium supplemented with 100 nM, 300 nM, or 1 microM GTN. EPCs expanded without
      GTN served as controls (n=10). In vivo, GTN exposure significantly increased the
      percentage of circulating cells expressing the EPC marker CD34 and increased the
      susceptibility of expanded EPCs to apoptosis but had no impact on the phenotypic
      differentiation or migration of EPCs. Ex vivo, GTN exposure increased apoptosis
      while decreasing phenotypic differentiation, migration, and mitochondrial
      dehydrogenase activity of EPCs, compared with EPCs expanded in the absence of
      GTN. Taken together, these results suggest that continuous GTN therapy might
      impair EPC-mediated processes, an effect that could be detrimental in the setting
      of ischemic cardiovascular disease.

PMID- 16622040
TI  - Effects of anesthetics on mutant N-methyl-D-aspartate receptors expressed in
      Xenopus oocytes.
AB  - Alcohols, inhaled anesthetics, and some injectable anesthetics inhibit the
      function of N-methyl-d-aspartate (NMDA) receptors, but the mechanisms responsible
      for this inhibition are not fully understood. Recently, it was shown that ethanol
      inhibition of NMDA receptors was reduced by mutation of residues in the
      transmembrane (TM) segment 3 of the NR1 subunit (F639A) or in TM4 of the NR2A
      subunit (A825W), suggesting putative ethanol binding sites. We hypothesized that
      the actions of other anesthetics might also require these amino acids and
      evaluated the effects of anesthetics on the NMDA receptors expressed in Xenopus
      oocytes with two-electrode voltage-clamp recording. Effects of hexanol, octanol,
      isoflurane, halothane, chloroform, cyclopropane, 1-chloro-1,2,2
      trifluorocyclobutane, and xenon were reduced or eliminated in the mutant NMDA
      receptors, whereas the inhibitory effects of nitrous oxide, ketamine, and benzene
      were not affected by these mutations. Rapid applications of glutamate and glycine
      by a T-tube device provided activation time constants, which suggested different
      properties of ketamine and isoflurane inhibition. Thus, amino acids in TM3 and
      TM4 are important for the actions of many anesthetics, but nitrous oxide,
      benzene, and ketamine seem to have distinct mechanisms for inhibition of the NMDA
      receptors.

PMID- 16622041
TI  - Evolutionary appearance of H+-translocating pyrophosphatases.

PMID- 16622042
TI  - A cultural divide on the use of chemostats.

PMID- 16622043
TI  - Flagellar glycosylation - a new component of the motility repertoire?
AB  - The biosynthesis, assembly and regulation of the flagellar apparatus has been the
      subject of extensive studies over many decades, with considerable attention
      devoted to the peritrichous flagella of Escherichia coli and Salmonella enterica.
      The characterization of flagellar systems from many other bacterial species has
      revealed subtle yet distinct differences in composition, regulation and mode of
      assembly of this important subcellular structure. Glycosylation of the major
      structural protein, the flagellin, has been shown most recently to be an
      important component of numerous flagellar systems in both Archaea and Bacteria,
      playing either an integral role in assembly or for a number of bacterial
      pathogens a role in virulence. This review focuses on the structural diversity in
      flagellar glycosylation systems and demonstrates that as a consequence of the
      unique assembly processes, the type of glycosidic linkage found on archaeal and
      bacterial flagellins is distinctive.

PMID- 16622044
TI  - Phospholipase A in Gram-negative bacteria and its role in pathogenesis.
AB  - Phospholipase A (PLA) is one of the few enzymes present in the outer membrane of
      Gram-negative bacteria, and is likely to be involved in the membrane disruption
      processes that occur during host cell invasion. Both secreted and membrane-bound
      phospholipase A(2) activities have been described in bacteria, fungi and
      protozoa. Recently there have been increasing reports on the involvement of PLA
      in bacterial invasion and pathogenesis. This review highlights the latest
      findings on PLA as a virulence factor in Gram-negative bacteria.

PMID- 16622045
TI  - Expression of and secretion through the Aeromonas salmonicida type III secretion
      system.
AB  - Aeromonas salmonicida subsp. salmonicida is the aetiological agent of
      furunculosis, a disease of farmed and wild salmonids. The type III secretion
      system (TTSS) is one of the primary virulence factors in A. salmonicida. Using a
      combination of differential proteomic analysis and reverse transcriptase (RT)
      PCR, it is shown that A. salmonicida A449 induces the expression of TTSS proteins
      at 28 degrees C, but not at its more natural growth temperature of 17 degrees C.
      More modest increases in expression occur at 24 degrees C. This temperature
      induced up-regulation of the TTSS in A. salmonicida A449 occurs within 30 min of
      a growth temperature increase from 16 to 28 degrees C. Growth conditions such as
      low-iron, low pH, low calcium, growth within the peritoneal cavity of salmon and
      growth to high cell densities do not induce the expression of the TTSS in A.
      salmonicida A449. The only other known growth condition that induces expression
      of the TTSS is growth of the bacterium at 16 degrees C in salt concentrations
      ranging from 0.19 to 0.38 M NaCl. It is also shown that growth at 28 degrees C
      followed by exposure to low calcium results in the secretion of one of the TTSS
      effector proteins. This study presents a simple in vitro model for the expression
      of TTSS proteins in A. salmonicida.

PMID- 16622046
TI  - Exploring the role of the CTL epitope region of listeriolysin O in the
      pathogenesis of Listeria monocytogenes.
AB  - Listeria monocytogenes is a facultative intracellular bacterial pathogen
      responsible for severe opportunistic infections in humans and animals. The
      secreted cholesterol-dependent cytolysin, listeriolysin O (LLO), mediates
      phagosomal escape and allows bacterial growth in the cytosol of infected cells.
      In order to identify new LLO determinants participating in bacterial
      pathogenesis, this study focused on a major target of LLO proteolytic cleavage in
      vitro, the CTL epitope region (residues 91-99). Mutations were generated by site
      directed mutagenesis in the epitope or in the two clusters of positive charges
      flanking the epitope. Two LLO mutants (a single mutation K103A and a double
      mutation R89G, K90G) were normally and stably secreted by L. monocytogenes. In
      contrast, a mutant carrying four amino acid substitutions in the epitope itself
      (Y92K, D94A, E97K, Y98F) was highly susceptible to proteolytic degradation. While
      these three LLO mutant proteins showed a reduced haemolytic activity, they all
      promoted efficient phagosomal escape and intracellular multiplication in
      different cell types, and were non-cytotoxic. The deletion of the epitope
      (Delta91-99), as well as the substitution of two, three or four of the four
      lysine residues (K103 to K106) by alanine residues did not lead to the production
      of a detectable protein. These results confirm the lack of correlation between
      haemolytic activity and phagosomal membrane disruption. They reveal the
      importance of the 91-99 region in the production of a stable and functional LLO.
      LD(50) determinations in the mouse model suggest a possible link between LLO
      stability and virulence.

PMID- 16622048
TI  - Streptococcus pneumoniae enolase is important for plasminogen binding despite low
      abundance of enolase protein on the bacterial cell surface.
AB  - Enolase represents one of the anchorless surface proteins of Streptococcus
      pneumoniae and has previously been identified as a plasminogen-binding protein,
      endowing this pathogen with host proteolytic activity. In this study the mAb
      245,C-6 (IgG1) was produced in a BALB/c mouse after immunizing with a protein
      fraction from S. pneumoniae. The mAb reacted with recombinant pneumococcal
      enolase both under non-denaturing and denaturing conditions. The epitope for the
      mAb was mapped to residues (55)DKSRYGGLG(63) of pneumococcal enolase using a
      peptide array. By applying the previously reported structure of enolase, this
      epitope was localized in a surface-exposed loop in each of the monomers of the
      octameric enolase. Previous immunoelectron microscopic studies, using polyclonal
      rabbit antibodies against enolase, depicted enolase on the cell surface but did
      not quantify the amount of surface-exposed enolase on viable pneumococci. Here,
      flow cytometry revealed no binding of mAb 245,C-6 to viable pneumococci,
      including TIGR4 and its non-encapsulated isogenic mutant, and only a minor
      increase of fluorescence intensity was measured when the polyclonal anti-enolase
      antibodies were used. In contrast, control antibodies recognizing the choline
      binding proteins (CBPs) PspA and PspC showed high reactivities. The non
      encapsulated TIGR4 did not show increased levels of antibody binding for mAb
      245,C-6 or polyclonal anti-enolase antibodies, but revealed increased binding of
      polyclonal antibodies reacting with PspA or PspC. These results suggest that,
      compared to other surface-exposed proteins such as CBPs, the amount of enolase
      under the selected conditions is low. Flow cytometry, however, with FITC-labelled
      plasminogen demonstrated that the amount of surface-exposed enolase is important
      for plasminogen binding and, therefore, is also important for pneumococcal
      pathogenesis.

PMID- 16622049
TI  - Paired cysteine residues are required for high levels of the Helicobacter pylori
      autotransporter VacA.
AB  - The Helicobacter pylori vacuolating cytotoxin VacA shares homology in its C
      terminal domain with many autotransporter proteins, suggesting a similar
      mechanism of secretion. Like most autotransporters, VacA contains a single pair
      of cysteine residues located near the C-terminus of the passenger domain. This
      study aimed to investigate the role of these conserved cysteine residues. This
      involved changing each cysteine in the VacA passenger domain to serine,
      quantifying the effect on VacA levels and assessing toxin activity in H. pylori.
      It was shown that both cysteine residues were required for high VacA levels,
      although mutation of each cysteine reduced toxin amounts to differing extents,
      implying that their importance was not simply for intramolecular disulphide bond
      formation. Although less VacA was observed for the cysteine mutants, vacuolating
      activity was detected, showing that the cysteines were not required for VacA
      function.

PMID- 16622050
TI  - YopM of Yersinia enterocolitica specifically interacts with alpha1-antitrypsin
      without affecting the anti-protease activity.
AB  - It was previously shown that alpha1-antitrypsin (AAT) interacts with the type III
      secreted (T3S) EspB and EspD proteins of enteropathogenic Escherichia coli
      (EPEC), resulting in reduced functionality of the proteins. To determine if AAT
      is also able to interact with T3S proteins of other pathogens, the binding of AAT
      to Yop proteins of Yersinia enterocolitica was analysed. AAT did not interact
      with YopB or YopD, which have functions in type III translocation similar to EspB
      and EspD in EPEC, but specifically interacts with YopM, a member of the leucine
      rich repeat (LRR) family of proteins, in overlay and pull-down assays. To
      determine regions of YopM involved in AAT binding, various N- and C-terminally
      truncated versions of YopM were recombinantly expressed, and their ability to
      interact with AAT analysed. All versions tested were able to bind AAT, indicating
      that at least eight LRR of YopM are sufficient for AAT interaction. The main
      physiological role of AAT is to inhibit neutrophil elastase; however, elastase
      was efficiently inhibited by AAT in the presence and absence of YopM, indicating
      that YopM does not interfere with the anti-protease inhibition activity of AAT,
      and that the domain of AAT interacting with YopM is not identical to AAT's
      protease interaction domain. Furthermore, it was shown that elastase efficiently
      degrades YopM and other Yop proteins. The data suggest that AAT has additional
      functions in the host response against bacterial infections that are not related
      to its anti-protease activity.

PMID- 16622051
TI  - Functional characterization of the FimH adhesin from Salmonella enterica serovar
      Enteritidis.
AB  - Salmonella enterica serovar Enteritidis has emerged during the last 20 years as
      the major causative agent of food-borne gastroenteritis in humans and as the
      major infectious agent on poultry farms, replacing Salmonella enterica serovar
      Typhimurium as the dominant pathogenic serovar. Because adhesion to gut tissues
      and colonization of the alimentary tract, mediated in large part by the FimH
      adhesins located on type 1 fimbriae, is an important stage in the pathogenesis of
      both serovars, the binding properties of the FimH adhesins from these two
      enteropathogens were compared. Salmonella Enteritidis FimH protein and the
      Salmonella Typhimurium low-adhesive variant of this adhesin were expressed in
      Escherichia coli and the recombinant proteins were analysed for their ability to
      bind glycoproteins carrying different oligomannosidic structures and different
      types of eukaryotic cells. In static binding assays (ELISA and Western blotting)
      both FimH proteins bound equally well to all three tested glycoproteins (RNase B,
      horseradish peroxidase and mannan-BSA). In addition, no differences were found in
      the binding specificity of the FimH proteins and intact cells of Salmonella
      Enteritidis and Salmonella Typhimurium to human colon carcinoma or bladder cancer
      cells. The presence of the same amino acid residues at positions 61 (glycine) and
      118 (phenylalanine) and the similar binding properties of these two adhesins
      suggest that the newly described FimH protein of Salmonella Enteritidis
      represents the low-adhesive variant found in Salmonella Typhimurium. To study the
      binding specificity of Salmonella Enteritidis FimH protein further, direct
      kinetic analysis using surface plasmon resonance was performed. With this method
      it was found that Salmonella Enteritidis FimH adhesin bound with the highest K(d)
      value to high-mannose type N-glycans carried by RNase B; about 100 times lower
      K(d) values were obtained in the interactions with mannan-BSA and horseradish
      peroxidase.

PMID- 16622047
TI  - The phylogeny of Staphylococcus aureus - which genes make the best intra-species
      markers?
AB  - The ability to make informed decisions on the suitability of alternative marker
      loci is central for population and epidemiological investigations. This issue was
      addressed using Staphylococcus aureus as a model population by generating
      nucleotide sequence data from 33 gene fragments in a representative sample of 30
      strains. Supplementing the data with pre-existing multilocus sequence typing
      data, an intra-species tree based on approximately 17.8 kb of sequence was
      reconstructed and the goodness of fit of each individual gene tree was computed.
      No strong association was noted between gene function per se and phylogenetic
      reliability, but it is suggested that candidate loci should possess at least the
      average degree of nucleotide diversity for all genes in the genome. In the case
      of S. aureus this threshold is >1 % mean pairwise diversity.

PMID- 16622052
TI  - Identification of the sigmaE regulon of Salmonella enterica serovar Typhimurium.
AB  - The extracytoplasmic function sigma factor, sigma(E), has been shown to play a
      critical role in virulence of Salmonella enterica serovar Typhimurium (S.
      Typhimurium). The previously optimized two-plasmid system has been used to
      identify S. Typhimurium promoters recognized by RNA polymerase containing
      sigma(E). This method allowed identification of 34 sigma(E)-dependent promoters
      that direct expression of 62 genes in S. Typhimurium, 23 of which (including
      several specific for S. Typhimurium) have not been identified previously to be
      dependent upon sigma(E) in Escherichia coli. The promoters were confirmed in S.
      Typhimurium and transcriptional start points of the promoters were determined by
      S1-nuclease mapping. All the promoters contained sequences highly similar to the
      consensus sequence of sigma(E)-dependent promoters. The identified genes
      belonging to the S. Typhimurium sigma(E)-regulon encode proteins involved in
      primary metabolism, DNA repair systems and outer-membrane biogenesis, and
      regulatory proteins, periplasmic proteases and folding factors, proposed
      lipoproteins, and inner- and outer-membrane proteins with unknown functions.
      Several of these sigma(E)-dependent genes have been shown to play a role in
      virulence of S. Typhimurium.

PMID- 16622053
TI  - Genes involved in the methyl tert-butyl ether (MTBE) metabolic pathway of
      Mycobacterium austroafricanum IFP 2012.
AB  - Methyl tert-butyl ether (MTBE) is a persistent pollutant of surface and
      groundwater, and the reasons for its low biodegradability are poorly documented.
      Using one of the rare bacterial strains able to grow in the presence of MTBE,
      Mycobacterium austroafricanum IFP 2012, the protein profiles of crude extracts
      after growth in the presence of MTBE and glucose were compared by SDS-PAGE. Ten
      proteins with molecular masses of 67, 64, 63, 55, 50, 27, 24, 17, 14 and 11 kDa
      were induced after growth in the presence of MTBE. Partial amino acid sequences
      of N-terminal and internal peptide fragments of the 64 kDa protein were used to
      design degenerate oligonucleotide primers to amplify total DNA by PCR, yielding a
      DNA fragment that was used as a probe for cloning. A two-step cloning procedure
      was performed to obtain a 10 327 bp genomic DNA fragment containing seven ORFs,
      including a putative regulator, mpdR, and four genes, mpdC, orf1, mpdB and orf2,
      in the same cluster. The MpdB protein (64 kDa) was related to a flavoprotein of
      the glucose-methanol-choline oxidoreductase family, and the MpdC protein (55 kDa)
      showed a high similarity with NAD(P) aldehyde dehydrogenases. Heterologous
      expression of these gene products was performed in Mycobacterium smegmatis mc2
      155. The recombinant strain was able to degrade an intermediate of MTBE
      biodegradation, 2-methyl 1,2-propanediol, to hydroxyisobutyric acid. This is
      believed to be the first report of the cloning and characterization of a cluster
      of genes specifically involved in the MTBE biodegradation pathway of M.
      austroafricanum IFP 2012.

PMID- 16622054
TI  - Biofilm formation by Pseudomonas fluorescens WCS365: a role for LapD.
AB  - A role for the outer-membrane-associated LapA protein in early biofilm formation
      by Pseudomonas fluorescens WCS365 has previously been shown. This paper reports
      that lapD, a gene located adjacent to the lapA gene, also plays a role in biofilm
      formation. A mutation in lapD results in a conditional biofilm defect in a static
      assay - this biofilm phenotype is exacerbated when biofilm formation is assayed
      in a flow-cell system. Furthermore, a lapD mutation shows a partial defect in the
      transition from reversible to irreversible attachment, consistent with an early
      role for the lapD gene product in biofilm formation. LapD is shown to be
      localized to the inner membrane of P. fluorescens. The data show decreased LapA
      associated with the cell surface, but no apparent change in cytoplasmic levels of
      this protein or lapA transcription, in a lapD mutant. A model is proposed wherein
      the role of LapD in biofilm formation is modulating the secretion of the LapA
      adhesin.

PMID- 16622055
TI  - Unravelling the role of the ToxR-like transcriptional regulator WmpR in the
      marine antifouling bacterium Pseudoalteromonas tunicata.
AB  - The dark-green-pigmented marine bacterium Pseudoalteromonas tunicata produces
      several target-specific compounds that act against a range of common fouling
      organisms, including bacteria, fungi, protozoa, invertebrate larvae and algal
      spores. The ToxR-like regulator WmpR has previously been shown to regulate
      expression of bioactive compounds, type IV pili and biofilm formation phenotypes
      which all appear at the onset of stationary phase. In this study a comparison of
      survival under starvation or stress between the wild-type P. tunicata strain and
      a wmpR mutant (D2W2) does not suggest a role for WmpR in regulating starvation-
      and stress-resistant phenotypes such as those that may be required in stationary
      phase. Both proteomic [2-dimensional PAGE (2D-PAGE)] and transcriptomic (RNA
      arbitrarily primed PCR) studies were used to discover members of the WmpR
      regulon. 2D-PAGE identified 11 proteins that were differentially expressed by
      WmpR. Peptide sequence data were obtained for six of these proteins and
      identified using the draft P. tunicata genome as being involved in protein
      synthesis, amino acid transamination and ubiquinone biosynthesis, as well as
      hypothetical proteins. The transcriptomic analysis identified three genes
      significantly up-regulated by WmpR, including a TonB-dependent outer-membrane
      protein, a non-ribosomal peptide synthetase and a hypothetical protein. Under
      iron-limitation the wild-type showed greater survival than D2W2, indicating the
      importance of WmpR under these conditions. Results from these studies show that
      WmpR controls the expression of genes encoding proteins involved in iron
      acquisition and uptake, amino acid metabolism and ubiquinone biosynthesis in
      addition to a number of proteins with as yet unknown functions.

PMID- 16622056
TI  - Succinate-mediated catabolite repression control on the production of glycine
      betaine catabolic enzymes in Pseudomonas aeruginosa PAO1 under low and elevated
      salinities.
AB  - Glycine betaine (GB) and its immediate precursors choline and carnitine,
      dimethylsulfonioacetate, dimethylsulfoniopropionate, ectoine and proline were
      effective osmoprotectants for Pseudomonas aeruginosa, but pipecolate, trehalose
      and sucrose had no osmoprotective effect. GB was accumulated stably or
      transiently when succinate or glucose, respectively, was used as a carbon and
      energy source. The catabolite repression mediated by succinate occurred at both
      low and high salinities, and it did not involve the global regulators Vfr and
      Crc. A proteomic analysis showed that at least 21 proteins were induced when GB
      was used as a carbon and energy source, and provided evidence that succinate
      repressed the synthesis of all these proteins. Many of the proteins induced by GB
      (sarcosine oxidase, serine hydroxymethyltransferase and serine dehydratase) are
      involved in GB catabolism. In addition, GB uptake was stimulated at high medium
      osmolalities but it was insensitive to catabolite repression by succinate.
      Despite its ability to inhibit betaine catabolism, succinate did not allow any
      better growth of P. aeruginosa cells under hyperosmotic constraint. Conversely,
      as observed for cells supplied with glucose, a transient accumulation of GB was
      sufficient to provide a significant cell osmoprotection.

PMID- 16622057
TI  - Investigation of the physiological relationship between the cyanide-insensitive
      oxidase and cyanide production in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen which demonstrates
      considerable respiratory versatility, possessing up to five terminal oxidases.
      One oxidase, the cyanide-insensitive oxidase (CIO), has been previously shown to
      be resistant to the potent respiratory inhibitor cyanide, a toxin that is
      synthesized by this bacterium. This study investigated the physiological
      relationship between hydrogen cyanide production and the CIO. It was found that
      cyanide is produced in P. aeruginosa at similar levels irrespective of its
      complement of CIO, indicating that the CIO is not an obligatory electron sink for
      cyanide synthesis. However, MICs for cyanide and growth in its presence
      demonstrated that the CIO provides P. aeruginosa with protection against the
      effects of exogenous cyanide. Nevertheless, the presence of cyanide did not
      affect the viability of cio mutant strains compared to the wild-type during
      prolonged incubation in stationary phase. The detection of the fermentation end
      products acetate and succinate in stationary-phase culture supernatants suggests
      that P. aeruginosa, irrespective of its CIO complement, may in part rely upon
      fermentation for energy generation in stationary phase. Furthermore, the decrease
      in cyanide levels during incubation in sealed flasks suggested that active
      breakdown of HCN by the culture was taking place. To investigate the possibility
      that the CIO may play a role in pathogenicity, wild-type and cio mutant strains
      were tested in the paralytic killing model of Caenorhabditis elegans, a model in
      which cyanide is the principal toxic agent leading to nematode death. The CIO
      mutant had delayed killing kinetics, demonstrating that the CIO is required for
      full pathogenicity of P. aeruginosa in this animal model.

PMID- 16622058
TI  - A cyanobacterial strain with all chromosomal rRNA operons inactivated: a single
      nucleotide mutation of 23S rRNA confers temperature-sensitive phenotypes.
AB  - The presence of a multicopy chromosome, with each copy containing two rRNA
      operons (rrnA and rrnB), has been an obstacle to analysing mutated rRNA in
      Synechococcus PCC 7942. To create a system for expressing homogeneous mutated
      rRNA, the chromosomal rrn operons were sequentially inactivated and a final
      strain was successfully obtained with all the chromosomal rrn operons inactivated
      but carrying a replaceable multicopy plasmid containing a single rrn operon. The
      lag time required for growth response on dark/light shift of mutant strains with
      chromosomal rrnA or rrnB inactivated was increased 50 % over that of the wild
      type strain; however, the presence of the plasmid-borne rrn operon restored the
      lag time. The doubling time of mutant strains carrying only a functional rrnB
      operon, but not strains carrying only a functional rrnA operon, was significantly
      longer than that of the wild-type strain. A strain in which essentially all the
      cellular 23S rRNA contained the mutation C2588A was temperature sensitive at 16
      degrees C and 45 degrees C. Position C2588 is equivalent to C2611 of the
      peptidyltransferase centre in domain V of Escherichia coli 23S rRNA.

PMID- 16622059
TI  - Transcriptional regulation of the macs1-fadD1 operon encoding two acyl-CoA
      synthases involved in the physiological differentiation of Streptomyces
      coelicolor.
AB  - The long-chain acyl-CoA synthase (ACS) FadD1 plays an important role in timing
      the levels of antibiotic production in Streptomyces coelicolor. fadD1 and macs1,
      encoding a putative medium-chain ACS, are part of a two-gene operon, whose
      expression is induced during the stationary phase of growth. Here it is reported
      that transcription of the macs1-fadD1 operon is positively regulated by AcsR, a
      LuxR-type transcriptional regulator. In an acsR mutant, expression of the macs1
      fadD1 genes loses its normal up-regulation and the mutant becomes deficient in
      antibiotic production, in a clear correlation with the phenotype shown by a fadD1
      null mutant. The absence of macs1-fadD1 induction in the acsR mutant was restored
      by complementation with a wild-type copy of the acsR gene, showing a strict link
      between AcsR and induction of the macs1-fadD1 operon. Gel mobility shift assays
      and DNase I footprinting indicated that AcsR binds to specific sequences about
      +162 nucleotides downstream of the macs1 transcriptional start site. In the
      putative operator sequence three almost identical direct tandem repeats of seven
      nucleotides were identified where the central sequence is essential for AcsR
      recognition and binding. Transcriptional fusions of the divergent pacsR and
      pmacs1 promoters indicated that AcsR does not regulate its own transcription, and
      that it binds to the operator region to control exclusively the growth-phase
      induction of the macs1-fadD1 operon.

PMID- 16622060
TI  - Surface plasmon resonance-based interaction studies reveal competition of
      Streptomyces lividans type I signal peptidases for binding preproteins.
AB  - Type I signal peptidases (SPases) are responsible for the cleavage of signal
      peptides from secretory proteins. Streptomyces lividans contains four different
      SPases, denoted SipW, SipX, SipY and SipZ, having at least some differences in
      their substrate specificity. In this report in vitro preprotein
      binding/processing and protein secretion in single SPase mutants was determined
      to gain more insight into the substrate specificity of the different SPases and
      the underlying molecular basis. Results indicated that preproteins do not
      preferentially bind to a particular SPase, suggesting SPase competition for
      binding preproteins. This observation, together with the fact that each SPase
      could process each preprotein tested with a similar efficiency in an in vitro
      assay, suggested that there is no real specificity in substrate binding and
      processing, and that they are all actively involved in preprotein processing in
      vivo. Although this seems to be the case for some proteins tested, high-level
      secretion of others was clearly dependent on only one particular SPase
      demonstrating clear differences in substrate preference at the in vivo processing
      level. Hence, these results strongly suggest that there are additional factors
      other than the cleavage requirements of the enzymes that strongly affect the
      substrate preference of SPases in vivo.

PMID- 16622061
TI  - In vivo hydrolysis of S-adenosylmethionine induces the met regulon of Escherichia
      coli.
AB  - Regulation of methionine biosynthesis in Escherichia coli involves a complex of
      the MetJ aporepressor protein and S-adenosylmethionine (SAM) repressing
      expression of most genes in the met regulon. To test the role of SAM in the
      regulation of met genes directly, SAM pools were depleted by the in vivo
      expression of the cloned plasmid vector-based coliphage T3 SAM hydrolase (SAMase)
      gene. Cultures with in vivo SAMase activity were assayed for expression of the
      metA, B, C, E, F, H, J, K and R genes in cells grown in methionine-rich complete
      media as well as in defined media with and without l-methionine. In vivo SAMase
      activity dramatically induced expression between 11- and nearly 1000-fold
      depending on the gene assayed for all but metJ and metH, and these genes were
      induced over twofold. metJ : : Tn5 (aporepressor defective) and metK : : Tn5 (SAM
      synthetase impaired; produces <5 % of wild-type SAM) strains containing in vivo
      SAMase activity produced even higher met gene activity than that seen in
      comparably prepared cells with wild-type genes for all but metJ in a MetJ
      deficient background. The SAMase-mediated hyperinduction of metH in wild-type
      cells and of the met genes assayed in metJ : : Tn5 and metK : : Tn5 cells
      provokes questions about how other elements such as the MetR activator protein or
      factors beyond the met regulon itself might be involved in the regulation of
      genes responsible for methionine biosynthesis.

PMID- 16622062
TI  - Transcription factor NNR from Paracoccus denitrificans is a sensor of both nitric
      oxide and oxygen: isolation of nnr* alleles encoding effector-independent
      proteins and evidence for a haem-based sensing mechanism.
AB  - The nitrite reductase and nitric oxide reductase regulator (NNR) from Paracoccus
      denitrificans activates transcription in response to nitric oxide (NO). The
      mechanism of NO sensing has not been elucidated for NNR, or for any of its
      orthologues from the FNR/CRP family of transcriptional regulators. Using
      regulated expression of the nnr gene in Escherichia coli, evidence has now been
      obtained to indicate that activation of NNR by NO does not require de novo
      synthesis of the NNR polypeptide. In anaerobic cultures, NNR is inactivated
      slowly following removal of the source of NO. In contrast, exposure of
      anaerobically grown cultures to oxygen causes rapid inactivation of NNR,
      suggesting that the protein is inactivated directly by oxygen. By random and site
      directed mutagenesis, two variants of NNR were isolated (with substitutions of
      arginine at position 80) that show high levels of activity in anaerobic cultures
      in the absence of NO. These proteins remain substantially inactive in aerobic
      cultures, suggesting that the substitutions uncouple the NO- and oxygen
      signalling mechanisms, thus providing further evidence that NNR senses both
      molecules. Structural modelling suggested that Arg-80 is close to the C-helix
      that forms the monomer-monomer interface in other members of the FNR/CRP family
      and plays an important role in transducing the activating signal between the
      regulatory and DNA binding domains. Assays of NNR activity in a haem-deficient
      mutant of E. coli provided preliminary evidence to indicate that NNR activity is
      haem dependent.

PMID- 16622063
TI  - The replicative polymerases PolC and DnaE are required for theta replication of
      the Bacillus subtilis plasmid pBS72.
AB  - Plasmids are the tools of choice for studying bacterial functions involved in DNA
      maintenance. Here a genetic study on the replication of a novel, low-copy-number,
      Bacillus subtilis plasmid, pBS72, is reported. The results show that two plasmid
      elements, the initiator protein RepA and an iteron-containing origin, and at
      least nine host-encoded replication proteins, the primosomal proteins DnaB, DnaC,
      DnaD, DnaG and DnaI, the DNA polymerases DnaE and PolC, and the polymerase
      cofactors DnaN and DnaX, are required for pBS72 replication. On the contrary, the
      cellular initiators DnaA and PriA, the helicase PcrA and DNA polymerase I are
      dispensable. From this, it is inferred that pBS72 replication is of the theta
      type and is initiated by an original mechanism. Indirect evidence suggests that
      during this process the DnaC helicase might be delivered to the plasmid origin by
      the weakly active DnaD pathway stimulated by a predicted interaction between DnaC
      and a domain of RepA homologous to the major DnaC-binding domain of the cellular
      initiator DnaA. The plasmid pBS72 replication fork appears to require the same
      functions as the bacterial chromosome and the unrelated plasmid pAMbeta1. Most
      importantly, this replication machinery contains the two type C polymerases, PolC
      and DnaE. As the mechanism of initiation of the three genomes is substantially
      different, this suggests that both type C polymerases might be required in any
      Cairns replication in B. subtilis and presumably in other bacteria encoding PolC
      and DnaE.

PMID- 16622064
TI  - Electron transfer to nitrite reductase of Rhodobacter sphaeroides 2.4.3:
      examination of cytochromes c2 and cY.
AB  - The role of cytochrome c(2), encoded by cycA, and cytochrome c(Y), encoded by
      cycY, in electron transfer to the nitrite reductase of Rhodobacter sphaeroides
      2.4.3 was investigated using both in vivo and in vitro approaches. Both cycA and
      cycY were isolated, sequenced and insertionally inactivated in strain 2.4.3.
      Deletion of either gene alone had no apparent effect on the ability of R.
      sphaeroides to reduce nitrite. In a cycA-cycY double mutant, nitrite reduction
      was largely inhibited. However, the expression of the nitrite reductase gene nirK
      from a heterologous promoter substantially restored nitrite reductase activity in
      the double mutant. Using purified protein, a turnover number of 5 s(-1) was
      observed for the oxidation of cytochrome c(2) by nitrite reductase. In contrast,
      oxidation of c(Y) only resulted in a turnover of approximately 0.1 s(-1). The
      turnover experiments indicate that c(2) is a major electron donor to nitrite
      reductase but c(Y) is probably not. Taken together, these results suggest that
      there is likely an unidentified electron donor, in addition to c(2), that
      transfers electrons to nitrite reductase, and that the decreased nitrite
      reductase activity observed in the cycA-cycY double mutant probably results from
      a change in nirK expression.

PMID- 16622065
TI  - Nisin induction without nisin secretion.
AB  - Nisin Z, a post-translationally modified antimicrobial peptide of Lactococcus
      lactis, is positively autoregulated by extracellular nisin via the two-component
      regulatory proteins NisRK. A mutation in the nisin NisT transporter rendered L.
      lactis incapable of nisin secretion, and nisin accumulated inside the cells.
      Normally nisin is activated after secretion by the serine protease NisP in the
      cell wall. This study showed that when secretion of nisin was blocked,
      intracellular proteolytic activity could cleave the N-terminal leader peptide of
      nisin precursor, resulting in active nisin. The isolated cytoplasm of a non-nisin
      producer could also cleave the leader from the nisin precursor, showing that the
      cytoplasm of L. lactis cells does contain proteolytic activity capable of
      cleaving the leader from fully modified nisin precursor. Nisin could not be
      detected in the growth supernatant of the NisT mutant strain with a nisin-sensing
      strain (sensitivity 10 pg ml(-1)), which has a green fluorescent protein gene
      connected to the nisin-inducible nisA promoter and a functional nisin signal
      transduction circuit. Northern analysis of the NisT mutant cells revealed that
      even though the cells could not secrete nisin, the nisin-inducible promoter
      P(nisZ) was active. In a nisB or nisC background, where nisin could not be fully
      modified due to the mutations in the nisin modification machinery, the unmodified
      or partly modified nisin precursor accumulated in the cytoplasm. This immature
      nisin could not induce the P(nisZ) promoter. The results suggest that when active
      nisin is accumulated in the cytoplasm, it can insert into the membrane and from
      there extrude parts of the molecule into the pseudoperiplasmic space to interact
      with the signal-recognition domain of the histidine kinase NisK. Potentially,
      signal presentation via the membrane represents a general pathway for amphiphilic
      signals to interact with their sensors for signal transduction.

PMID- 16622066
TI  - An activated Ras protein alters cell adhesion by dephosphorylating Dictyostelium
      DdCAD-1.
AB  - RasG-regulated signal transduction has been linked to a variety of growth
      specific processes and appears to also play a role in the early development of
      Dictyostelium discoideum. In an attempt to uncover some of the molecular
      components involved in Ras-mediated signalling, several proteins have been
      described previously, including the cell adhesion molecule DdCAD-1, whose
      phosphorylation state was affected by the expression of the constitutively
      activated RasG, RasG(G12T). Here it has been shown that a cadA null strain lacks
      the phosphoproteins that were tentatively identified as DdCAD-1, confirming its
      previous designation. Further investigation revealed that cells expressing
      RasG(G12T) exhibited increased cell-cell cohesion, concomitant with reduced
      levels of DdCAD-1 phosphorylation. This increased cohesion was DdCAD-1-dependent
      and was correlated with increased localization of DdCAD-1 at the cell surface.
      DdCAD-1 phosphorylation was also found to decrease during Dictyostelium
      aggregation. These results revealed a possible role for protein phosphorylation
      in regulating DdCAD-1-mediated cell adhesion during early development. In
      addition, the levels of DdCAD-1 protein were substantially reduced in a rasG null
      cell line. These results indicate that RasG affects both the expression and
      dephosphorylation of DdCAD-1 during early development.

PMID- 16622067
TI  - D-Galactose induces cellulase gene expression in Hypocrea jecorina at low growth
      rates.
AB  - Lactose (1,4-O-beta-d-galactopyranosyl-d-glucose) is a soluble and economic
      carbon source for the industrial production of cellulases or recombinant proteins
      by Hypocrea jecorina (anamorph Trichoderma reesei). The mechanism by which
      lactose induces cellulase formation is not understood. Recent data showed that
      the galactokinase step is essential for cellulase induction by lactose, but
      growth on d-galactose alone does not induce cellulases. Consequently, the
      hypothesis was tested that d-galactose may be an inducer only at a low growth
      rate, which is typically observed when growing on lactose. Carbon-limited
      chemostat cultivations of H. jecorina were therefore performed at different
      dilution rates with d-galactose, lactose, galactitol and d-glucose. Cellulase
      gene expression was monitored by using a strain carrying a fusion between the
      cbh2 (encoding cellobiohydrolase 2, Cel6A) promoter region and the Aspergillus
      niger glucose oxidase gene and by identification of the two major
      cellobiohydrolases Cel7A and Cel6A. The results show that d-galactose indeed
      induces cbh2 gene transcription and leads to Cel7A and Cel6A accumulation at a
      low (D=0.015 h(-1)) but not at higher dilution rates. At the same dilution rate,
      growth on d-glucose did not lead to cbh2 promoter activation or Cel6A formation
      but a basal level, lower than that observed on d-galactose, was detected for the
      carbon-catabolite-derepressible Cel7A. Lactose induced significantly higher
      cellulase levels at 0.015 h(-1) than d-galactose and induced cellulases even at
      growth rates up to 0.042 h(-1). Results of chemostats with an equimolar mixture
      of d-galactose and d-glucose essentially mimicked the behaviour on d-galactose
      alone, whereas an equimolar mixture of d-galactose and galactitol, the first
      intermediate of a recently described second pathway of d-galactose catabolism,
      led to cellulase induction at D=0.030 h(-1). It is concluded that d-galactose
      indeed induces cellulases at low growth rate and that the operation of the
      alternative pathway further increases this induction. However, under those
      conditions lactose is still a superior inducer for which the mechanism remains to
      be clarified.

PMID- 16622068
TI  - Water channels are important for osmotic adjustments of yeast cells at low
      temperature.
AB  - The importance of aquaporin expression in water permeability in Saccharomyces
      cerevisiae was assessed by measuring the osmotic water permeability coefficient
      (P(f)) and the activation energies (E(a)) from both hypo- and hypertonic
      experiments performed with whole protoplasts from four strains differing in
      aquaporin level of expression: parental, double-deleted and overexpressing AQY1
      or AQY2. Double-deleted (lower P(f)) and AQY1-overexpressing strains (higher
      P(f)) presented linear Arrhenius plots with E(a) consistent with fluxes mainly
      through the lipids [16.3 kcal mol(-1) (68.2 kJ mol(-1))] and with a strong
      contribution of channels [9.6 kcal mol(-1) (40.2 kJ mol(-1))], respectively. The
      Arrhenius plots for the parental (swelling experiments) and overexpressing AQY2
      strains (swelling and shrinking experiments) were not linear, presenting a break
      point with a change in slope around 23 degrees C. The E(a) values for these
      strains, calculated for temperatures ranging from 7 to 23 degrees C, were lower
      [9.5 kcal mol(-1) (39.7 kJ mol(-1))] than the values obtained from 23 to 38
      degrees C [17 kcal mol(-1) (71.1 kJ mol(-1))]. This behaviour indicates that only
      in the lower temperature range did the water fluxes occur predominantly via the
      water channels. The permeabilities for each strain relative to the deletion
      strain show that an increase in permeability due to the presence of aquaporins
      was more relevant at low temperatures. Following our results, we propose that
      water channels play an important role for osmotic adjustment of yeast cells at
      low temperature.

PMID- 16622070
TI  - Delta-aminolaevulinic acid synthesis is required for virulence of the wheat
      pathogen Stagonospora nodorum.
AB  - Delta-aminolaevulinic acid (ALA) is synthesized in fungi by ALA synthase, a key
      enzyme in the synthesis of haem. The requirement for ALA synthase in Stagonospora
      nodorum to cause disease in wheat was investigated. The single gene encoding ALA
      synthase (Als1) was cloned and characterized. Expression analysis determined that
      Als1 transcription was up-regulated during germination and also towards the
      latter stages of the infection. The Als1 gene was further characterized by
      homologous gene replacement. The inactivation of Als1 resulted in strains
      producing severely stunted germ tubes leading quickly to death. The strains could
      be recovered by supplementation with 33 microM ALA. Pathogenicity assays revealed
      the als1 strains were essentially non-pathogenic, inferring a key role for the
      synthesis of ALA during in planta growth. Supplementing the strains with ALA
      restored growth in vitro and also pathogenicity for up to 5 days after
      inoculation. Further examination by inoculating the als1 strains onto wounded
      leaves found that pathogenicity was only partially restored, suggesting that host
      derived in planta levels of ALA are not sufficient to support growth. This study
      has identified a key role for fungal ALA synthesis during infection and revealed
      its potential as an antifungal target.

PMID- 16622069
TI  - Vacuolar protein sorting receptor in Schizosaccharomyces pombe.
AB  - The mechanism by which soluble proteins, such as carboxypeptidase Y, reach the
      vacuole in Saccharomyces cerevisiae is very similar to the mechanism of lysosomal
      protein sorting in mammalian cells. Vps10p is a receptor for transport of soluble
      vacuolar proteins in S. cerevisiae. vps10(+), a gene encoding a homologue of S.
      cerevisiae PEP1/VPS10, has been identified and deleted from the fission yeast
      Schizosaccharomyces pombe. Deletion of the vps10(+) gene resulted in missorting
      and secretion of Sch. pombe vacuolar carboxypeptidase Cpy1p, indicating that it
      is required for targeting Cpy1p to the vacuole. Sch. pombe Vps10p (SpVps10p) is a
      type I transmembrane protein and its C-terminal cytoplasmic tail domain is
      essential for Cpy1p transport to the vacuole. Cells expressing green fluorescent
      protein-tagged SpVps10p produced a punctate pattern of fluorescence, indicating
      that SpVps10p was largely localized in the Golgi compartment. In addition, Sch.
      pombe vps26(+), vps29(+) and vps35(+), encoding homologues of the S. cerevisiae
      retromer components VPS26, VPS29 and VPS35, were identified and deleted.
      Fluorescence microscopy demonstrated that SpVps10p mislocalized to the vacuolar
      membrane in these mutants. These results indicate that the vps26(+), vps29(+) and
      vps35(+) gene products are required for retrograde transport of SpVps10p from the
      prevacuolar compartment back to the Golgi in Sch. pombe cells.

PMID- 16622071
TI  - Multiple gene genealogical analyses suggest divergence and recent clonal
      dispersal in the opportunistic human pathogen Candida guilliermondii.
AB  - Candida guilliermondii is a haploid opportunistic pathogen accounting for about 2
      % of human blood yeast infections. Recent analyses using multilocus enzyme
      electrophoresis and karyotyping suggest that strains from human sources
      traditionally designated C. guilliermondii in fact include at least two species,
      C. guilliermondii and Candida fermentati. However, the patterns of molecular
      variation within and between these two species remain largely unknown. In this
      study, DNA fragments were sequenced from five genes for each of 37 strains
      collected from Canada, China, the Philippines and Tanzania. The analyses
      identified significant sequence differences between C. guilliermondii and C.
      fermentati. The five gene genealogies showed no apparent incongruence, suggesting
      a predominantly clonal reproductive structure for both species in nature. Indeed,
      two large clones of C. guilliermondii were identified, with one from Ontario,
      Canada, and the other from China. Interestingly, the results indicate that
      strains currently designated C. guilliermondii may contain additional divergent
      lineages. On the practical side, the results revealed several diagnostic
      molecular markers that can be used in clinical microbiology laboratories to
      distinguish C. guilliermondii and C. fermentati. The multiple gene genealogical
      analyses conducted here revealed significant divergence and clonal dispersal in
      this important pathogenic yeast complex.

PMID- 16622072
TI  - Construction and functional analysis of fatty acid desaturase gene disruptants in
      Candida albicans.
AB  - Polyunsaturated fatty acids (PUFAs), including linoleic acid (C18 : 2) and alpha
      linolenic acid (C18 : 3), are major components of membranes. PUFAs are produced
      from monounsaturated fatty acids by several fatty acid desaturases (FADs) in many
      fungi, but Saccharomyces cerevisiae, Schizosaccharomyces pombe and humans do not
      have these enzymes. Although the fungal pathogen Candida albicans produces C18 :
      2 and C18 : 3, the enzymes that synthesize them have not yet been investigated.
      In this report, two ORFs, CaFAD2 and CaFAD3, were identified based on their
      homology to other yeast FADs, and CaFAD2 and CaFAD3 gene disruptants were
      constructed. Cafad2Delta and Cafad3Delta lost their ability to produce C18 : 2
      and C18 : 3, respectively. Furthermore, S. cerevisiae cells expressing CaFad2p
      converted palmitoleic acid (C16 : 1) and C18 : 1 to hexadecadienoic acid (C16 :
      2) and C18 : 2, respectively, and CaFad3p-expressing cells converted C18 : 2 to
      C18 : 3. These results strongly supported that CaFAD2 encodes the Delta12 FAD and
      that CaFAD3 encodes the omega3 FAD. However, phenotypic analysis demonstrated
      that the presence of these PUFAs did not affect the virulence to mice, or
      morphogenesis in the culture media used to induce morphological change of C.
      albicans.

PMID- 16622073
TI  - Chimeras of the ABC drug transporter Cdr1p reveal functional indispensability of
      transmembrane domains and nucleotide-binding domains, but transmembrane segment
      12 is replaceable with the corresponding homologous region of the non-drug
      transporter Cdr3p.
AB  - The molecular basis of the broad substrate recognition and the transport of
      substrates by Cdr1p, a major drug efflux protein of Candida albicans, is not well
      understood. To investigate the role of transmembrane domains and nucleotide
      binding domains (NBDs) of Cdr1p in drug transport, two sets of protein chimeras
      were constructed: one set between homologous regions of Cdr1p and the non-drug
      transporter Cdr3p, and another set consisting of Cdr1p variants comprising either
      two N- or two C-terminal NBDs of Cdr1p. The replacement of either the N- or the C
      terminal half of Cdr1p by the homologous segments of Cdr3p resulted in non
      functional recombinant strains expressing chimeric proteins. The results suggest
      that the chimeric protein could not reach the plasma membrane, probably because
      of misfolding and subsequent cellular trafficking problems, or the rapid
      degradation of the chimeras. As an exception, the replacement of transmembrane
      segment 12 (TMS12) of Cdr1p by the corresponding region of Cdr3p resulted in a
      functional chimera which displayed unaltered affinity for all the tested
      substrates. The variant protein comprising either two N-terminal or two C
      terminal NBDs of Cdr1p also resulted in non-functional recombinant strains.
      However, the N-terminal NBD variant, which also showed poor cell surface
      localization, could be rescued to cell surface, if cells were grown in the
      presence of drug substrates. The rescued chimera remained non-functional, as was
      evident from impaired ATPase and efflux activities. Taken together, the results
      suggest that the two NBDs of Cdr1p are asymmetric and non-exchangeable and that
      the drug efflux by Cdr1p involves complex interactions between the two halves of
      the protein.

PMID- 16622074
TI  - OSU-03012 promotes caspase-independent but PERK-, cathepsin B-, BID-, and AIF
      dependent killing of transformed cells.
AB  - We determined one mechanism by which the putative phosphoinositide-dependent
      kinase (PDK)-1 inhibitor 2-amino-N-{4-[5-(2-phenanthrenyl)-3-(trifluoromethyl)-1H
      pyrazol-1-yl]-phenyl}acetamide (OSU-03012) killed primary human glioma and other
      transformed cells. OSU-03012 caused a dose-dependent induction of cell death that
      was not altered by p53 mutation, expression of ERBB1 vIII, or loss of phosphatase
      and tensin homolog deleted on chromosome 10 function. OSU-03012 promoted cell
      killing to a greater extent in glioma cells than in nontransformed astrocytes.
      OSU-03012 and ionizing radiation caused an additive, caspase-independent
      elevation in cell killing in 96-h viability assays and true radiosensitization in
      colony formation assays. In a cell type-specific manner, combined exposure to OSU
      03012 with a mitogen-activated protein kinase kinase 1/2 inhibitor,
      phosphoinositide 3-kinase/AKT inhibitors, or parallel molecular interventions
      resulted in a greater than additive induction of cell killing that was
      independent of AKT activity and caspase function. OSU-03012 lethality as a single
      agent or when combined with signaling modulators was not modified in cells
      lacking expression of BIM or of BAX/BAK. OSU-03012 promoted the release of
      cathepsin B from the lysosomal compartment and release of AIF from mitochondria.
      Loss of BH3-interacting domain (BID) function, overexpression of BCL(XL), and
      inhibition of cathepsin B function suppressed cell killing and apoptosis-inducing
      factor (AIF) release from mitochondria. In protein kinase R-like endoplasmic
      reticulum kinase-/- cells, the lethality of OSU-03012 was attenuated which
      correlated with reduced cleavage of BID and with suppression of cathepsin B and
      AIF release into the cytosol. Our data demonstrate that OSU-03012 promotes glioma
      cell killing that is dependent on endoplasmic reticulum stress, lysosomal
      dysfunction, and BID-dependent release of AIF from mitochondria, and whose
      lethality is enhanced by irradiation or by inhibition of protective signaling
      pathways.

PMID- 16622075
TI  - Uncorrected refractive error.

PMID- 16622076
TI  - Mozart in AVF testing.

PMID- 16622077
TI  - How does visual acuity change over time in adults with high myopia?

PMID- 16622078
TI  - How blinding is pathological myopia?

PMID- 16622079
TI  - The approach to bilateral simultaneous isolated optic neuritis.

PMID- 16622080
TI  - The changing face of leprosy.

PMID- 16622081
TI  - "Sight for more eyes".

PMID- 16622082
TI  - Prevalence and causes of blindness and visual impairment in Muyuka: a rural
      health district in South West Province, Cameroon.
AB  - AIM: To estimate the prevalence and causes of blindness and visual impairment in
      the population aged 40 years and over in Muyuka, a rural district in the South
      West Province of Cameroon. METHODS: A multistage cluster random sampling
      methodology was used to select 20 clusters of 100 people each. In each cluster
      households were randomly selected and all eligible people had their visual acuity
      (VA) measured by an ophthalmic nurse. Those with VA <6/18 were examined by an
      ophthalmologist. RESULTS: 1787 people were examined (response rate 89.3%). The
      prevalence of binocular blindness was 1.6% (95% CI: 0.8% to 2.4%), 2.2% (1.% to
      3.1%) for binocular severe visual impairment, and 6.4% (5.0% to 7.8%) for
      binocular visual impairment. Cataract was the main cause of blindness (62.1%),
      severe visual impairment (65.0%), and visual impairment (40.0%). Refractive error
      was an important cause of severe visual impairment (15.0%) and visual impairment
      (22.5%). The cataract surgical coverage for people was 55% at the <3/60 level and
      33% at the <6/60 level. 64.3% of eyes operated for cataract had poor visual
      outcome (presenting VA<6/60). CONCLUSIONS: Strategies should be developed to make
      cataract services affordable and accessible to the population in the rural areas.
      There is an urgent need to improve the outcome of cataract surgery. Refractive
      error services should be provided at the community level.

PMID- 16622083
TI  - Visual outcomes for high myopic patients with or without myopic maculopathy: a 10
      year follow up study.
AB  - AIM: To evaluate the visual outcomes for high myopic patients aged 40 years and
      older with or without myopic maculopathy. METHODS: 552 high myopic (spherical
      equivalent < or =-6.0D or axial length > or =26.5 mm) patients were enrolled in
      the study, 230 cases with myopic maculopathy (at least lacquer cracks were
      identified) and 322 cases without maculopathy. The initial and final visual
      acuity (VA) (after 10 years) was compared between two groups. Additionally, the
      relation between sex, age, refraction, and axial length was analysed to find out
      the possible risk factors associated with visual outcome in myopic maculopathy.
      RESULTS: In 92% of patients aged 40-49, final VA was better than 20/40 after 10
      years of follow up. However, it was less than 40% in those older than 60 years.
      For more than 50% of patients older than 40 years of age with maculopathy, their
      vision had decreased more than two lines in Snellen VA after 10 years of follow
      up, compared to only 4.3% of analogues without myopic maculopathy. Patchy atrophy
      and choroidal neovascularisation in myopic macular degeneration groups showed
      poorer visual outcome than lacquer cracks in the macular lesion group. Other
      prognostic factors of visual outcomes were myopic refraction, axial length, and
      ageing. CONCLUSIONS: Clearly, prognosis for patients with maculopathy is poorer
      than for those without maculopathy. Refractive status, axial length, and ageing
      are the main factors involved in determining the visual outcomes. The macular
      grading also affects the visual outcome for high myopic patients.

PMID- 16622084
TI  - Clinical profile of simultaneous bilateral optic neuritis in adults.
AB  - AIM: To establish the clinical profile of simultaneous bilateral optic neuritis
      in adults, the efficacy of steroid therapy, extent of visual recovery, and
      neurological outcome. METHODS: The authors performed a retrospective review of
      records of patients referred to a neuro-ophthalmology service with acute
      bilateral optic neuritis from 2000-4. Exclusion criteria included previous
      multiple sclerosis or myelopathy, known systemic disorders or medications
      associated with optic neuropathy, uveitis, or neoplasm. Patients received
      intravenous methylprednisolone followed by oral prednisone. Visual acuity (logMAR
      conversion), mean deviation (dB) for visual fields, percentage of Ishihara plates
      seen, ophthalmoscopy, and neurological evaluation were recorded at baseline and
      at 6 months or 12 months. Owing to strong correlation for visual loss between
      eyes, the results for the worse eye in each patient were analysed. RESULTS: 11
      men and four women, with an age range of 18-64 years, had bilateral decreased
      vision, 12 with pain on eye movement. Except for one patient, no aetiology was
      found. All patients had normal neurological evaluations, average visual acuity
      1.71 (SD 0.55), colour vision 2.7% (SD 9.9%), and mean deviation -25.35 dB (SD 
      7.95 dB). Both optic nerves showed abnormal signal on magnetic resonance imaging.
      14 patients improved and their last average visual acuity, colour vision, and
      mean deviation were 0.36 (SD 0.54), 69% (SD 46%), and -7.05 dB (SD 8.40 dB),
      respectively. No patient developed a neurological problem during the follow up
      with a mean of 11 months. CONCLUSION: Idiopathic acute bilateral optic neuritis
      without myelopathy occasionally occurs in adults. Vision recovers with
      corticosteroid therapy and during the first year neurological dysfunction will
      frequently not occur.

PMID- 16622085
TI  - Incidence of ocular morbidity among multibacillary leprosy patients during a 2
      year course of multidrug therapy.
AB  - AIM: To evaluate the incidence of and risk factors for ocular complications in
      multibacillary (MB) leprosy patients during their 2 year, fixed duration,
      multidrug therapy (MDT). METHODS: Periodic eye examinations were conducted
      prospectively on a cohort of 301 consecutive newly diagnosed MB patients every 6
      months during their 2 year course of MDT. Incidence of ocular pathology was
      calculated as the number of events per person year of event free follow up of
      patients who did not have the specific finding at baseline. RESULTS: 292 (97%)
      patients had one or more follow up visits. The incidence of lagophthalmos was
      1.2%/patient year (95% CI 0.5% to 2.8%); corneal opacity was 7.4%/patient year
      (95% CI 5.1% to 10.6%); uveal involvement was 5.1%/patient year (95% CI 3.3% to
      7.8%), and cataract that reduced vision to 6/18 or less was seen in 4.3%/patient
      year (95% CI 2.7% to 6.9%) of patients. Overall, 23 individuals (5.8%/patient
      year, 95% CI 3.9 to 8.8) developed leprosy related potentially blinding pathology
      during the 2 years of MDT. CONCLUSIONS: Approximately 20% of patients with MB
      leprosy can be expected to develop ocular complications of leprosy during a 2
      year course of MDT, many (11%) of which are potentially vision threatening.
      Ophthalmological monitoring to detect and treat ocular complications at defined
      intervals during MDT is indicated.

PMID- 16622087
TI  - Agreement between optometrists and ophthalmologists on clinical management
      decisions for patients with glaucoma.
AB  - BACKGROUND/AIMS: Although optometrists have become an accepted part of the team
      in many hospital glaucoma clinics, their decision making ability has not been
      assessed formally. This study aims to document the accuracy and safety of
      clinical work undertaken by optometrists in the hospital setting by investigating
      their management decisions on follow up of patients with glaucoma. METHODS: Four
      optometrists and three medical clinicians examined 50 patients each. Clinical
      findings were recorded as usual in the hospital records but management decisions
      were documented separately on a specially designed data collection form.
      Subsequently, the patient records and clinical findings were reviewed
      retrospectively and independently by two consultant ophthalmologists, who were
      masked to the management decisions of the optometrists and medical clinicians.
      The consultants' management decisions were then compared with those made by the
      optometrists and medical clinicians. Percentage agreements were computed together
      with kappa (kappa), or weighted kappa, statistics where appropriate. RESULTS:
      Agreement between consultants and optometrists was 55% (kappa = 0.33) for
      evaluation of visual field status, 79% (kappa = 0.67) for medical management, 72
      98% for other aspects of patient management, and 78% (weighted kappa = 0.35) for
      scheduling of next clinic appointment. Very similar levels of agreement were
      found between consultants and medical clinicians. CONCLUSION: Agreement between
      optometrists and consultants, in glaucoma clinical decision making, was at least
      as good as that between medical clinicians and consultants. Within an appropriate
      environment, optometrists can safely work as part of the hospital glaucoma team
      in outpatient clinics.

PMID- 16622086
TI  - Comparison of a non-preserved 0.1% T-Gel eye gel (single dose unit) with a
      preserved 0.1% T-Gel eye gel (multidose) in ocular hypertension and glaucomatous
      patients.
AB  - AIM: This comparative, open design, phase III study was to assess the non
      inferiority of the non-preserved T-Gel 0.1% single dose unit (SDU) versus its
      preserved multidose (MD) reference. METHODS: 175 patients with bilateral POAG or
      OHT were randomised: 87 patients were to receive one drop daily of T-Gel 0.1% MD
      and 88 patients were to receive one drop daily of T-Gel 0.1% SDU, for a treatment
      period of 12 weeks. The primary efficacy variable was the change in intraocular
      pressure (IOP) in the worse eye between the baseline and the last assessment.
      Subjective and objective ocular signs as well as adverse events were recorded for
      safety. Global tolerance was assessed by the investigator and by the patient.
      RESULTS: The mean percentage reduction from baseline IOP was 24% for both
      treatments groups, which was consistent with previous studies. The safety results
      were comparable in both treatment groups. Because of gel formulation, mild short
      lasting episodes of blurred vision occurred for about 20% of patients. The global
      tolerance assessment reported that both treatments were well tolerated.
      CONCLUSION: The overall study results demonstrated that T-Gel 0.1% SDU is not
      inferior to T-Gel 0.1% MD.

PMID- 16622088
TI  - Star testing: a novel evaluation of intraocular lens optical quality.
AB  - BACKGROUND: Despite the importance of optical quality of an intraocular lens
      (IOL) on visual outcomes following cataract surgery, objective data on their
      optical quality are not readily available, and manufacturing standards are
      industry regulated. The star test is a classic test of optical quality based on
      examination of the Airy disc and expanded diffraction rings of a point source of
      light, used mainly for telescope and microscope objectives. METHODS: A physical
      model eye cell allowed star testing of IOLs under conditions similar to the
      optical environment in which they operate. 18 IOLs were tested and results
      compared to actual images produced by these lenses in the model eye cell.
      Quantitative measures of star testing performance were developed. RESULTS: The
      optical performance of the IOLs varied, some performing very poorly. Most lenses
      (13/17) performed better in reverse orientation, while aberrations induced by the
      haptics of foldable IOLs were also detected. There was excellent correlation
      between actual images formed and star testing parameters. CONCLUSION: Star
      testing IOLs was a novel biomedical application of a centuries old, inexpensive
      method. A concerning variation of optical quality was found, suggesting IOL
      optical performance data should be more readily available. Independent, authority
      mandated IOL optical quality standards should be developed, and results readily
      available to ophthalmologists.

PMID- 16622089
TI  - Impact of age related macular degeneration on quality of life.
AB  - AIMS: To describe the impact of age related macular degeneration (AMD) on quality
      of life and explore the association with vision, health, and demographic
      variables. METHODS: Adult participants diagnosed with AMD and with impaired
      vision (visual acuity <6/12) were assessed with the Impact of Vision Impairment
      (IVI) questionnaire. Participants rated the extent that vision restricted
      participation in activities affecting quality of life and completed the Short
      Form General Health Survey (SF-12) and a sociodemographic questionnaire. RESULTS:
      The mean age of the 106 participants (66% female) was 83.6 years (range 64-98).
      One quarter had mild vision impairment, (VA<6/12-6/18) and 75% had moderate or
      severely impaired vision. Participants reported from at least "a little" concern
      on 23 of the 32 IVI items including reading, emotional health, mobility, and
      participation in relevant activities. Those with mild and moderate vision
      impairment were similarly affected but significantly different from those with
      severe vision loss (p<0.05). Distance vision was associated with IVI scores but
      not age, sex, or duration of vision loss. CONCLUSION: AMD affects many quality of
      life related activities and not just those related to reading. Referral to low
      vision care services should be considered for people with mild vision loss and
      worse.

PMID- 16622090
TI  - Prevalence and associations of anisometropia and aniso-astigmatism in a
      population based sample of 6 year old children.
AB  - AIM: To study the distribution of anisometropia and aniso-astigmatism in young
      Australian children, together with clinical and ocular biometry relations.
      METHOD: The Sydney Myopia Study examined 1765 predominantly 6 year old children
      from 34 randomly selected Sydney schools during 2003-4. Keratometry, cycloplegic
      autorefraction, and questionnaire data were collected. RESULTS: Spherical
      equivalent (SE) anisometropia (> or =1 dioptre) prevalence was 1.6% (95%
      confidence interval (CI) 1.1% to 2.4%). Aniso-astigmatism (>or =1D) prevalence
      was 1.0% (CI: 0.6% to 1.6%). Both conditions were significantly more prevalent
      among moderately hyperopic (SE > or =2.0D) than mildly hyperopic (SE 0.5-1.9D)
      children. Myopic children (SE < or =-0.5D) had higher anisometropia prevalence.
      Neither condition varied by age, sex, or ethnicity. In multivariate analyses,
      anisometropia was significantly associated with amblyopia, odds ratio (OR) 29,
      (CI: 8.7 to 99), exotropia (OR 7.7, CI: 1.2 to 50), and neonatal intensive care
      unit (NICU) admission (OR 3.6, CI: 1.1 to 12.6). Aniso-astigmatism was
      significantly associated with amblyopia (OR 8.2, CI: 1.4 to 47), maternal age >35
      years (OR 4.0, CI: 1.3 to 11.9), and NICU admission (OR 4.6, CI: 1.2 to 17.2).
      Anisometropia resulted from relatively large interocular differences in axial
      length (p<0.0001) and anterior chamber depth (p = 0.0009). Aniso-astigmatism
      resulted from differences in corneal astigmatism (p<0.0001). CONCLUSION: In this
      predominantly 6 year old population, anisometropia and aniso-astigmatism were
      uncommon, had important birth and biometry associations, and were strongly
      related to amblyopia and strabismus.

PMID- 16622092
TI  - The in vitro activity of selected defensins against an isolate of Pseudomonas in
      the presence of human tears.
AB  - BACKGROUND/AIMS: Pseudomonas aeruginosa is a major cause of severe bacterial
      keratitis and remains a difficult clinical entity to treat successfully with the
      current arsenal of antimicrobial agents. Defensins are small cationic peptides
      with broad in vitro antimicrobial activity and are potential ocular therapeutic
      agents. The authors characterised the in vitro activity of defensins NP-1 and NP
      3a against P aeruginosa in the presence of human tears. METHODS: A clinical
      Pseudomonas isolate was grown to mid-log phase, and 1 x 10(6 )colony forming
      units were exposed to the peptides (200 microg/ml) for up to 2 hours in the
      presence of varying concentrations (10-70%) of human tears. RESULTS: For both
      peptides in the presence of 10% tears, >3 log units of killing was achieved
      within 30 minutes. In 70% tears, NP-1 produced >1 log unit of killing at 2 hours,
      indicating that, although reduced, its activity remained significant. In 20%
      tears, NP-3a demonstrated 2 log units of killing at 2 hours; however, the
      antimicrobial activity of this defensin was completely inhibited in the presence
      of 70% tears. CONCLUSION: These in vitro data suggest that while the microbicidal
      activity of some defensins may be diminished at the ocular surface in vivo,
      significant activity is still possible with certain peptides.

PMID- 16622091
TI  - Adult xanthogranulomatous disease of the orbit and ocular adnexa: new
      immunohistochemical findings and clinical review.
AB  - BACKGROUND/AIMS: Adult xanthogranulomatous disease involving the ocular tissues
      is rare and poorly understood. Adult onset xanthogranuloma (AOX), adult onset
      asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX),
      and Erdheim-Chester disease (ECD) are the four syndromes within this disorder,
      which is diagnosed by characteristic histopathology. Experience with eight cases
      prompted a multi-institutional effort to study the histopathology,
      immunohistochemistry, clinical findings, and systemic associations in this
      disorder. METHODS: 22 cases, including histopathological slides, were compiled.
      Published reports were identified by an English language Medline search (1966
      2005) and review of reference citations. Each case in this series and the
      literature was classified as one of four syndromes and then analysed for age
      onset, sex, skin xanthoma, orbital location, immune dysfunction, internal organ
      and bone lesions, treatment, and outcome. The histopathology in each of these
      cases was reviewed by two pathologists. Immunhistochemical stains (CD3, CD4, CD8,
      L26) were performed in 14 cases where unstained slides were available. RESULTS:
      137 cases were compiled. There was no sex or age difference between syndromes.
      AOX, AAPOX, NBX affect the anterior orbit, ECD tends to be diffuse and
      intraconal. Skin lesions are found in all the syndromes. Immune dysfunction was
      noted in all cases of AAPOX and NBX; 11% of NBX and all ECD patients had internal
      organ disease. Treatment included surgery, corticosteroids, other
      chemotherapeutic agents, radiotherapy, and combinations of these. No AOX or AAPOX
      deaths occurred; 66% of ECD patients died. All 22 cases had xanthoma cells; most
      had Touton giant cells. Lymphocytes were present in all cases and occurred as
      aggregates (mostly in AAPOX) or diffuse populations mixed with fibroblasts
      (mostly in ECD). Immunohistochemistry revealed the majority of these to be CD8+.
      Necrosis was most marked in NBX. CONCLUSION: Adult xanthogranuloma of the orbit
      is rare, making prospective evaluation or meta-analysis impossible. The best
      treatment is unknown but seems to be with multiagent chemotherapy guided by
      histopathological, immunohistochemical, and systemic findings.

PMID- 16622093
TI  - High density lipoprotein mediated lipid efflux from retinal pigment epithelial
      cells in culture.
AB  - BACKGROUND/AIM: [corrected] The transport of radiolabelled photoreceptor outer
      segments (POS) lipids was investigated by cultured retinal pigment epithelial
      cells (RPE). Phagocytosis of POS by the RPE is essential to maintain the health
      and function of the photoreceptors in vivo. POS are phagocytised at the apical
      cell surface of RPE cells. Phagocytised POS lipids may be either recycled to the
      photoreceptors for reincorporation into new POS or they may be transported to the
      basolateral surface for efflux into the circulation. RESULTS: The authors have
      demonstrated that high density lipoprotein (HDL) stimulates efflux of
      radiolabelled lipids, of POS origin, from the basal surface of RPE cells in
      culture. Effluxed lipids bind preferentially to HDL species of low and high
      molecular weight. Effluxed radiolabelled phosphotidyl choline was the major
      phospholipid bound to HDL, with lesser amounts of phosphatidyl ethanolamine,
      phosphatidyl inosotol. Effluxed radiolabelled triglycerides, cholesterol, and
      cholesterol esters also bound to HDL. Lipid free apolipoprotein A-I (apoA-I) and
      apoA-I containing vesicles also stimulate lipid efflux. CONCLUSION: The findings
      suggest a role for HDL and apoA-I in regulating lipid and cholesterol transport
      from RPE cells that may influence the pathological lipid accumulation associated
      with age related macular degeneration.

PMID- 16622094
TI  - An experimental study of the elastic properties of the human Bruch's membrane
      choroid complex: relevance to ageing.
AB  - AIM: To investigate the mechanical properties (stress-strain relation,
      elasticity, hysteresis, response to stress spikes and drops) of isolated human
      Bruch's membrane-choroid, as well as the effect of ageing and aged related
      macular degeneration (AMD). METHODS: 13 Bruch's membrane-choroid complexes were
      obtained from human donors (21-97 years). Two samples (aged 85 and 95) showed
      signs of AMD including large, soft drusen, choroidal neovascularisation, and/or
      disciform scars. Various hydrostatic pressures (stress) were applied to the
      choroidal surface of mid-peripheral samples mounted in a modified open Ussing
      chamber. Linear scans of the tissue were recorded by optical coherence tomography
      (OCT) and the pressure induced deformation (strain), elasticity, hysteresis, and
      response to pressure spikes and drops measured. RESULTS: The elasticity of human
      Bruch's membrane-choroid complex decreased linearly with ageing (p<0.001) after
      the age of 21 with an approximate reduction of 1% per year. The decrease was not
      exaggerated in AMD. The recoil capacity of Bruch's membrane-choroid was not
      affected by ageing. The response to pressure spikes/drops was similar in age
      matched normal and AMD eyes. The results suggest that although the aged induced
      decrease in Bruch's membrane elasticity may contribute to breaks in this membrane
      in AMD leading to neovascularisation this is not sufficient. The presence of
      other factors is required for its development. CONCLUSION: The elasticity of
      Bruch's membrane-choroid complex decreases with age while recoil capacity does
      not. The decrease was not exaggerated in AMD.

PMID- 16622097
TI  - Papilloedema secondary to otitic hydrocephalus.

PMID- 16622096
TI  - The future of glaucoma clinics.
AB  - The number of patients seen with glaucoma related pathologies is predicted to
      increase significantly over the next few years as a result of an ageing
      population, increased optometric screening, and raised public awareness. In
      addition, the recent glaucoma literature proposes more aggressive management of
      ocular hypertension, open angle glaucoma, and narrow angle pathologies. This will
      overburden many glaucoma services and demands a reappraisal of current management
      strategies. Using a database of patients compiled from their tertiary referral
      glaucoma service as an example, the authors discuss the current controversies
      relating to each glaucoma subtype, encompassing issues relating to disease
      prognosis, efficacy of treatment, and resource management. They also suggest a
      range of strategies aimed at streamlining glaucoma clinics. Examples include
      shared care schemes, multidisciplinary teams, clinic guidelines/protocols, and
      alteration of clinic review times. The predicted effect of such schemes on clinic
      workloads is discussed, together with any existing validation.

PMID- 16622095
TI  - The management of retinal vein occlusion: is interventional ophthalmology the way
      forward?
AB  - Retinal vein occlusions (RVO) are the second commonest sight threatening vascular
      disorder. Despite its frequency treatments for RVO are unsatisfactory and include
      several that have not been tested by large, well designed, prospective,
      randomised controlled trials. There is also the lack of long term follow up in
      many of the available small uncontrolled studies, and the timings of
      interventions are haphazard. This review aims to evaluate the current knowledge
      relating to the pathogenesis, suggested treatments for the different types of
      RVO, and their complications. Isovolaemic haemodilution is of limited benefit and
      should be avoided in patients with concurrent cardiovascular, renal, or pulmonary
      morbidity. Evidence to date does not support any therapeutic benefit from radial
      optic neurotomy, optic nerve decompression, or arteriovenous crossing sheathotomy
      on its own. Vitrectomy combined with intravenous thrombolysis may offer promise
      for central RVO. Similarly, vitrectomy combined with arteriovenous sheathotomy
      intravenous tissue plasminogen activator may offer benefits for branch RVO. RVOs
      occur at significantly high frequency to allow future prospective randomised
      controlled studies to be conducted to evaluate the role of different therapeutic
      modalities singly or in combination.

PMID- 16622098
TI  - Diagnosis of Treponema pallidum in vitreous samples using real time polymerase
      chain reaction.

PMID- 16622099
TI  - Viscogonioplasty in patients with chronic narrow angle glaucoma.

PMID- 16622101
TI  - Choriocarcinoma metastatic to the choroid.

PMID- 16622100
TI  - Acanthamoeba detection in the anterior chamber.

PMID- 16622102
TI  - Spontaneous resolution of retinoschisis and consequent development of retinal
      detachment in highly myopic eye.

PMID- 16622103
TI  - Congenital stationary night blindness associated with mutations in GRM6 encoding
      glutamate receptor MGluR6.

PMID- 16622104
TI  - Metastastic choriocarcinoma causing cavernous sinus syndrome.

PMID- 16622105
TI  - Primary posterior continuous capsulorhexis; a new technique.

PMID- 16622106
TI  - Infectious crystalline keratopathy associated with intravitreal and posterior sub
      Tenon triamcinolone acetonide injections.

PMID- 16622107
TI  - HLA typing of a Hong Kong Chinese family with intermediate uveitis.

PMID- 16622108
TI  - Congenital iris ectropion as an indicator of variant aniridia.

PMID- 16622109
TI  - Fourth time lucky: a case of multiple recurrence of a macular hole.

PMID- 16622110
TI  - The role of Mohs excision in periocular basal cell carcinoma.

PMID- 16622111
TI  - Fourth biannual report of the Cochrane Haematological Malignancies Group.

PMID- 16622112
TI  - Surrogate endpoints: wishful thinking or reality?

PMID- 16622113
TI  - Cancer survivorship: the interface of aging, comorbidity, and quality care.

PMID- 16622114
TI  - Assessing risk: does this patient have prostate cancer?

PMID- 16622115
TI  - Negative Women's Health Initiative findings stir consternation, debate among
      researchers.

PMID- 16622116
TI  - Intraperitoneal therapy for advanced ovarian cancer: will it become standard
      care?

PMID- 16622117
TI  - Stat bite: Age-specific incidence and mortality rates for ovarian cancer, 1998
      2002.

PMID- 16622118
TI  - Researchers target unfolded protein response in cancerous tumor growth.

PMID- 16622119
TI  - NCCN issues first guidelines for deep vein thrombosis treatment in cancer
      patients.

PMID- 16622120
TI  - Evaluation of prostate-specific antigen declines for surrogacy in patients
      treated on SWOG 99-16.
AB  - BACKGROUND: The identification of surrogate endpoints that can replace true
      outcome endpoints is crucial to the rapid evaluation of new cancer drugs.
      Retrospective analyses of phase II and III trials in metastatic androgen
      independent prostate cancer have shown associations between declines in serum
      prostate-specific antigen (PSA) levels and survival. We evaluated PSA changes as
      potential surrogate markers for survival by using data from a clinical trial.
      METHODS: Men with androgen-independent prostate cancer were randomly assigned to
      either docetaxel/estramustine (D/E) or mitoxantrone/prednisone (M/P) treatment on
      Southwest Oncology Group Protocol 99-16. Of 674 eligible patients, 551 had a
      baseline PSA measurement and at least one PSA measurement during the first 3
      months on protocol. PSA level declines of 5%-90% and PSA velocity at 1, 2, and 3
      months were tested for surrogacy by using three statistical criteria: Prentice's
      criteria, the proportion of treatment effect explained, and the proportion of
      variation explained. All statistical tests were two-sided. RESULTS: Three-month
      PSA level declines of 20%-40%, a 2-month PSA decline of 30%, and PSA velocity at
      2 and 3 months met all three surrogacy criteria. For example, a 3-month PSA
      decline of at least 30% was associated with a more than 50% decrease in the risk
      of death compared with the lack of such a decline (hazard ratio [HR] = 0.43, 95%
      confidence interval [CI] = 0.34 to 0.55; P < .001), and the increased risk of
      death for men treated with M/P compared with D/E (HR = 1.24, 95% CI = 1.02 to
      1.51; P = .032) lost statistical significance after adjustment for this
      surrogate, whereas the decrease in risk of death associated with a 3-month 30%
      PSA decline remained statistically significant after adjustment for treatment.
      PSA level declines of 50%, commonly reported in clinical trials, did not meet the
      criteria for surrogacy. CONCLUSIONS: Several PSA measures satisfied the surrogacy
      criteria for survival in a retrospective analysis of data from SWOG 99-16.
      However, these measures await prospective validation in future clinical trials of
      chemotherapy in men with androgen-independent prostate cancer.

PMID- 16622121
TI  - Functional limitations in elderly female cancer survivors.
AB  - BACKGROUND: The elderly population, including many who are long-term cancer
      survivors, is increasing. Aspects of quality of life in elderly cancer survivors
      are not well understood. METHODS: Subjects were women who enrolled in a
      population-based cohort study in 1986. At follow-up in 1997, 25,719 women, at a
      median age of 72 years, reported on functional limitations. We used logistic
      regression to calculate prevalence odds ratios (ORs) and proportional hazards
      regression to calculate prevalence ratios (PRs) for associations between cancer
      survivor status and functional limitations, adjusting for baseline (precancer)
      characteristics including obesity, smoking, and diabetes. RESULTS: Women who were
      cancer survivors for less than 2 years reported the most functional limitations,
      but long-term (5 or more years) cancer survivors remained more likely than cohort
      members who had not had cancer to report that they were unable to do heavy
      household work (42% of 1068 5-year survivors, versus 31% of 23 501 who never had
      cancer, multivariable OR = 1.47, 95% confidence interval [CI] = 1.27 to 1.69; PR
      = 1.22, 95% CI = 1.10 to 1.34), unable to walk a half mile (26% versus 19%, OR =
      1.31, 95% CI = 1.1 to 1.54; PR = 1.16, 95% CI = 1.02 to 1.32), and unable to walk
      up and down stairs (9% versus 6%, OR = 1.34, 95% CI = 1.05 to 1.72; PR = 1.25,
      95% CI = 1.00 to 1.56). The increased prevalence of functional limitations was
      apparent for 5-year survivors of breast cancer and also certain other cancers.
      CONCLUSIONS: Our findings support the need to target elderly cancer survivors for
      interventions to maintain or regain physical function.

PMID- 16622122
TI  - Assessing prostate cancer risk: results from the Prostate Cancer Prevention
      Trial.
AB  - BACKGROUND: Prostate-specific antigen (PSA) testing is the primary method used to
      diagnose prostate cancer in the United States. Methods to integrate other risk
      factors associated with prostate cancer into individualized risk prediction are
      needed. We used prostate biopsy data from men who participated in the Prostate
      Cancer Prevention Trial (PCPT) to develop a predictive model of prostate cancer.
      METHODS: We included 5519 men from the placebo group of the PCPT who underwent
      prostate biopsy, had at least one PSA measurement and a digital rectal
      examination (DRE) performed during the year before the biopsy, and had at least
      two PSA measurements performed during the 3 years before the prostate biopsy.
      Logistic regression was used to model the risk of prostate cancer and high-grade
      disease associated with age at biopsy, race, family history of prostate cancer,
      PSA level, PSA velocity, DRE result, and previous prostate biopsy. Risk equations
      were created from the estimated logistic regression models. All statistical tests
      were two-sided. RESULTS: A total of 1211 (21.9%) men were diagnosed with prostate
      cancer by prostate biopsy. Variables that predicted prostate cancer included
      higher PSA level, positive family history of prostate cancer, and abnormal DRE
      result, whereas a previous negative prostate biopsy was associated with reduced
      risk. Neither age at biopsy nor PSA velocity contributed independent prognostic
      information. Higher PSA level, abnormal DRE result, older age at biopsy, and
      African American race were predictive for high-grade disease (Gleason score > or
      =7) whereas a previous negative prostate biopsy reduced this risk. CONCLUSIONS:
      This predictive model allows an individualized assessment of prostate cancer risk
      and risk of high-grade disease for men who undergo a prostate biopsy.

PMID- 16622123
TI  - Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2
      Carrier Cohort Study (IBCCS).
AB  - BACKGROUND: Multiparity, young age at first childbirth, and breast-feeding are
      associated with a reduced risk of breast cancer in the general population. The
      breast cancer predisposition gene, BRCA1, regulates normal cell differentiation.
      Because mammary gland cells divide and differentiate during pregnancy,
      reproductive factors may influence breast cancer risk in BRCA1/2 mutation
      carriers differently than they do in noncarriers. METHODS: We performed a
      retrospective cohort study of 1601 women in the International BRCA1/2 Carrier
      Cohort Study cohort, all of whom carried a mutation in BRCA1 or BRCA2.
      Information on reproductive factors was obtained from a questionnaire. At the
      time of interview 853 subjects were classified with breast cancer. Data were
      analyzed by using a weighted cohort approach. All statistical tests were two
      sided. RESULTS: There was no statistically significant difference in the risk of
      breast cancer between parous and nulliparous women. Among parous women, an
      increasing number of full-term pregnancies was associated with a statistically
      significant decrease in the risk of breast cancer (Ptrend = .008); risk was
      reduced by 14% (95% confidence interval [CI] = 6% to 22%) for each additional
      birth. This association was the same for carriers of mutations in either BRCA1 or
      BRCA2 and was restricted to women older than 40 years. In BRCA2 mutation
      carriers, first childbirth at later ages was associated with an increased risk of
      breast cancer compared with first childbirth before age 20 years (20-24 years,
      hazard ratio [HR] = 2.33 [95% CI = 0.93 to 5.83]; 25-29 years, HR = 2.68 [95% CI
      = 1.02 to 7.07]; > or = 30 years, HR = 1.97 [95% CI = 0.67 to 5.81]), whereas in
      BRCA1 mutation carriers, first childbirth at age 30 years or later was associated
      with a reduced risk of breast cancer compared with first childbirth before age 20
      years (HR = 0.58 [95% CI = 0.36 to 0.94]). Neither history of interrupted
      pregnancies (induced abortions or miscarriage) nor history of breast-feeding was
      statistically significantly associated with the risk of breast cancer.
      CONCLUSIONS: BRCA1 and BRCA2 mutation carriers older than 40 years show a similar
      reduction in breast cancer risk with increasing parity as non-carriers.

PMID- 16622124
TI  - Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor.
AB  - BACKGROUND: We previously synthesized a novel s-triazine derivative, ZSTK474 [2
      (2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine], that
      strongly inhibited the growth of tumor cells. We identified its molecular target,
      investigated its effects on cellular signaling pathways, and examined its
      antitumor efficacy and toxicity in vivo. METHODS: We used COMPARE analysis of
      chemosensitivity measurements from 39 human cancer cell lines and identified
      phosphatidylinositol 3-kinase (PI3K) as a molecular target for ZSTK474. PI3K was
      immunoprecipitated from A549 cell lysates, and its activity was measured by
      assessing the incorporation of 32P into phosphatidylinositol. We used the crystal
      structure of the PI3K-LY294002 complex to model the binding of ZSTK474 to PI3K
      (where LY294002 is a known PI3K inhibitor). PI3K downstream activity was analyzed
      by immunoblotting. Antitumor activity of ZSTK474 was examined against A549, PC-3,
      and WiDr xenografts in nude mice. Phosphorylation of Akt, a serine/threonine
      protein kinase and a major signaling component downstream of PI3K, was assessed
      in vivo by immunohistochemistry. RESULTS: PI3K was identified as a molecular
      target for ZSTK474 by COMPARE analysis. We confirmed that ZSTK474 directly
      inhibited PI3K activity more efficiently than the PI3K inhibitor LY294002. At
      concentrations of 1 microM, ZSTK474 and LY2194002 reduced PI3K activity to 4.7%
      (95% confidence interval [CI] = 3.2% to 6.1%) and 44.6% (95% CI = 38.9% to
      50.3%), respectively, of the untreated control level. Molecular modeling of the
      PI3K-ZSTK474 complex indicated that ZSTK474 could bind to the ATP-binding pocket
      of PI3K. ZSTK474 inhibited phosphorylation of signaling components downstream
      from PI3K, such as Akt and glycogen synthase kinase 3beta, and mediated a
      decrease in cyclin D1 levels. ZSTK474 administered orally to mice had strong
      antitumor activity against human cancer xenografts without toxic effects in
      critical organs. Akt phosphorylation was reduced in xenograft tumors after oral
      administration of ZSTK474. CONCLUSION: ZSTK474 is a new PI3K inhibitor with
      strong antitumor activity against human cancer xenografts without toxic effects
      in critical organs. ZSTK474 merits further investigation as an anticancer drug.

PMID- 16622125
TI  - Long-term cancer risk among Swedish women with cosmetic breast implants: an
      update of a nationwide study.
AB  - Epidemiologic evidence does not support a consistently increased cancer risk
      among women with cosmetic breast implants, but few studies have assessed risk
      beyond 15 years. Swedish women who underwent cosmetic breast implantation for the
      first time between January 1, 1965, and December 31, 1993 (N = 3486), were
      followed through December 31, 2002. Cancer incidence was ascertained through the
      nationwide Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95%
      confidence intervals (CIs) were calculated to compare cancer incidence of women
      with implants with women in the general population. Mean follow-up among women
      with breast implants was 18.4 years (range = 0.1-37.8 years). The incidence of
      breast cancer was below expectation (SIR = 0.7, 95% CI = 0.6 to 1.0), whereas
      lung cancer was above expectation (SIR = 2.2, 95% CI = 1.3 to 3.4). With respect
      to cancer overall and all other specific cancer sites, including brain cancer and
      sarcoma, non-Hodgkin lymphoma, and multiple myeloma, no statistically
      significantly increased or decreased SIRs were observed. Stratification by
      duration of follow-up revealed no statistically significantly increased or
      decreased SIR, with the exception of a two- to threefold excess of lung cancer
      among women followed for more than 15 years, which would be expected due to the
      high prevalence of smoking among the Swedish women with implants in our study.

PMID- 16622126
TI  - Re: Risk of thyroid cancer after exposure to (131)I in childhood.

PMID- 16622127
TI  - Response of a KIT-positive extra-abdominal fibromatosis to imatinib mesylate and
      KIT genetic analysis.

PMID- 16622128
TI  - Re: Risks of cancer and families.

PMID- 16622129
TI  - The cover. Young Girl in Pink.

PMID- 16622130
TI  - Studies explore stroke's gender gap.

PMID- 16622131
TI  - Researchers seek roots of resilience in children.

PMID- 16622132
TI  - Interplay of genes and environment found in adolescents' alcohol abuse.

PMID- 16622133
TI  - Group ponders genomics and public health.

PMID- 16622134
TI  - Parathyroid hormone, vitamin D, and calcium intake.

PMID- 16622135
TI  - Use of socioeconomic status in health research.

PMID- 16622136
TI  - Clinical decision support systems and antibiotic prescribing.

PMID- 16622137
TI  - Adiponectin and risk of congestive heart failure.

PMID- 16622138
TI  - Midlife body mass index and total mortality.

PMID- 16622139
TI  - Neuropsychological and renal effects of dental amalgam in children: a randomized
      clinical trial.
AB  - CONTEXT: No randomized trials have been published that address the concern that
      inhalation of mercury vapor released by amalgam dental restorations causes
      adverse health effects. OBJECTIVE: To compare the neuropsychological and renal
      function of children whose dental caries were restored using amalgam or mercury
      free materials. DESIGN AND SETTING: The New England Children's Amalgam Trial was
      a 2-group randomized safety trial involving 5 community health dental clinics in
      Boston, Mass, and 1 in Farmington, Me, between September 1997 and March 2005.
      PARTICIPANTS AND INTERVENTION: A total of 534 children aged 6 to 10 years at
      baseline with no prior amalgam restorations and 2 or more posterior teeth with
      caries were randomly assigned to receive dental restoration of baseline and
      incident caries during a 5-year follow-up period using either amalgam (n=267) or
      resin composite (n =267) materials. MAIN OUTCOME MEASURES: The primary
      neuropsychological outcome was 5-year change in full-scale IQ scores. Secondary
      outcomes included tests of memory and visuomotor ability. Renal glomerular
      function was measured by creatinine-adjusted albumin in urine. RESULTS: Children
      had a mean of 15 tooth surfaces (median, 14) restored during the 5-year period
      (range, 0-55). Assignment to the amalgam group was associated with a
      significantly higher mean urinary mercury level (0.9 vs 0.6 microg/g of
      creatinine at year 5, P<.001). After adjusting for randomization stratum and
      other covariates, no statistically significant differences were found between
      children in the amalgam and composite groups in 5-year change in full-scale IQ
      score (3.1 vs 2.1, P = .21). The difference in treatment group change scores was
      1.0 (95% confidence interval, -0.6 to 2.5) full-scale IQ score point. No
      statistically significant differences were found for 4-year change in the general
      memory index (8.1 vs 7.2, P = .34), 4-year change in visuomotor composite (3.8 vs
      3.7, P = .93), or year 5 urinary albumin (median, 7.5 vs 7.4 mg/g of creatinine,
      P = .61). CONCLUSIONS: In this study, there were no statistically significant
      differences in adverse neuropsychological or renal effects observed over the 5
      year period in children whose caries were restored using dental amalgam or
      composite materials. Although it is possible that very small IQ effects cannot be
      ruled out, these findings suggest that the health effects of amalgam restorations
      in children need not be the basis of treatment decisions when choosing
      restorative dental materials. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00065988.

PMID- 16622140
TI  - Neurobehavioral effects of dental amalgam in children: a randomized clinical
      trial.
AB  - CONTEXT: Dental (silver) amalgam is a widely used restorative material containing
      50% elemental mercury that emits small amounts of mercury vapor. No randomized
      clinical trials have determined whether there are significant health risks
      associated with this low-level mercury exposure. OBJECTIVE: To assess the safety
      of dental amalgam restorations in children. DESIGN: A randomized clinical trial
      in which children requiring dental restorative treatment were randomized to
      either amalgam for posterior restorations or resin composite instead of amalgam.
      Enrollment commenced February 1997, with annual follow-up for 7 years concluding
      in July 2005. SETTING AND PARTICIPANTS: A total of 507 children in Lisbon,
      Portugal, aged 8 to 10 years with at least 1 carious lesion on a permanent tooth,
      no previous exposure to amalgam, urinary mercury level <10 microg/L, blood lead
      level <15 microg/dL, Comprehensive Test of Nonverbal Intelligence IQ > or =67,
      and with no interfering health conditions. INTERVENTION: Routine, standard-of
      care dental treatment, with one group receiving amalgam restorations for
      posterior lesions (n = 253) and the other group receiving resin composite
      restorations instead of amalgam (n = 254). MAIN OUTCOME MEASURES: Neurobehavioral
      assessments of memory, attention/concentration, and motor/visuomotor domains, as
      well as nerve conduction velocities. RESULTS: During the 7-year trial period,
      children had a mean of 18.7 tooth surfaces (median, 16) restored in the amalgam
      group and 21.3 (median, 18) restored in the composite group. Baseline mean
      creatinine-adjusted urinary mercury levels were 1.8 microg/g in the amalgam group
      and 1.9 microg/g in the composite group, but during follow-up were 1.0 to 1.5
      microg/g higher in the amalgam group than in the composite group (P<.001). There
      were no statistically significant differences in measures of memory, attention,
      visuomotor function, or nerve conduction velocities (average z scores were very
      similar, near zero) for the amalgam and composite groups over all 7 years of
      follow-up, with no statistically significant differences observed at any time
      point (P values from .29 to .91). Starting at 5 years after initial treatment,
      the need for additional restorative treatment was approximately 50% higher in the
      composite group. CONCLUSIONS: In this study, children who received dental
      restorative treatment with amalgam did not, on average, have statistically
      significant differences in neurobehavioral assessments or in nerve conduction
      velocity when compared with children who received resin composite materials
      without amalgam. These findings, combined with the trend of higher treatment need
      later among those receiving composite, suggest that amalgam should remain a
      viable dental restorative option for children. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00066118.

PMID- 16622141
TI  - Education, 15-year risk factor progression, and coronary artery calcium in young
      adulthood and early middle age: the Coronary Artery Risk Development in Young
      Adults study.
AB  - CONTEXT: The inverse association between education and cardiovascular disease is
      well established, but little is known about the relationship between education
      and subclinical disease, which is free from medical access and treatment-related
      influences, or about possible mediating pathways for these relationships.
      OBJECTIVE: To examine the association of education with coronary artery calcium
      (CAC), an indicator of subclinical atherosclerosis, and cardiovascular risk
      factors, and their changes as potential mediators. DESIGN, SETTING, AND
      PARTICIPANTS: A population-based, prospective, observational study (Coronary
      Artery Risk Development in Young Adults [CARDIA]) of 2913 eligible participants
      (44.9% black; 53.9% women) recruited from 4 metropolitan areas (Birmingham, Ala;
      Chicago, Ill; Minneapolis, Minn; and Oakland, Calif) in both the baseline (1985
      1986, ages 18-30 years) and year 15 examinations (2000-2001, ages 33-45 years).
      Education (year 15) was classified into less than high school (n = 128), high
      school graduate (n = 498), some college (n = 902), college graduate (n = 764),
      and more than college (n = 621). MAIN OUTCOME MEASURE: Presence of CAC, measured
      twice by computed tomography (mean total Agatston score >0) at year 15. RESULTS:
      Overall CAC prevalence in this sample was 9.3%. After adjusting for age, race,
      and sex, the odds ratios (ORs) for having CAC were 4.14 (95% confidence interval
      [CI], 2.33-7.35) for less than high school education, 1.89 (95% CI, 1.23-2.91)
      for high school graduate, 1.47 (95% CI, 0.99-2.19) for some college, and 1.24
      (95% CI, 0.84-1.85) for college graduate compared with those participants with
      more than a college education (P for trend<.001). This was also consistent within
      each of the 4 race-sex groups. Adjustment for baseline systolic blood pressure,
      smoking, waist circumference, physical activity, and total cholesterol reduced
      the ORs to 2.61 (95% CI, 1.40-4.85) for less than high school, 1.38 (95% CI, 0.88
      2.17) for high school graduate, 1.17 (95% CI, 0.78-1.77) for some college, and
      1.13 (95% CI, 0.76-1.69) for college graduate compared with more than a college
      education (P for trend = .01), and only slightly attenuated by further adjustment
      for 15-year changes in risk factors. CONCLUSION: Education was inversely
      associated with the prevalence of CAC, an association partially explained by
      baseline risk factors and minimally by 15-year changes in risk factors.

PMID- 16622142
TI  - Second-order peer review of the medical literature for clinical practitioners.
AB  - CONTEXT: Most articles in clinical journals are not appropriate for direct
      application by individual clinicians. OBJECTIVE: To create a second order of
      clinical peer review for journal articles to determine which articles are most
      relevant for specific clinical disciplines. DESIGN AND SETTING: A 2-stage
      prospective observational study in which research staff reviewed all issues of
      over 110 (number has varied slightly as new journals were added or discarded from
      review but number has always been over 110) clinical journals and selected each
      article that met critical appraisal criteria from January 2003 through the
      present. Practicing physicians were recruited from around the world, excluding
      Northern Ontario, to the McMaster Online Rating of Evidence (MORE) system and
      registered as raters according to their clinical disciplines. An automated system
      assigned each qualifying article to raters for each pertinent clinical
      discipline, and recorded their online assessments of the articles on 7-point
      scales (highest score, 7) of relevance and newsworthiness (defined as useful new
      information for physicians). Rated articles fed an online alerting service, the
      McMaster Premium Literature Service (PLUS). Physicians from Northern Ontario were
      invited to register with PLUS and then receive e-mail alerts about articles
      according to MORE system peer ratings for their own discipline. Online access by
      PLUS users of PLUS alerts, raters' comments, article abstracts, and full-text
      journal articles was automatically recorded. MAIN OUTCOME MEASURES: Clinical
      rater recruitment and performance. Relevance and newsworthiness of journal
      articles to clinical practice in the discipline of the rating physician. RESULTS:
      Through October 2005, MORE had 2139 clinical raters, and PLUS had 5892 articles
      with 45 462 relevance ratings and 44 724 newsworthiness ratings collected since
      2003. On average, clinicians rated systematic review articles higher for
      relevance to practice than articles with original evidence and lower for useful
      new information. Primary care physicians rated articles lower than did
      specialists (P<.05). Of the 98 physicians who registered for PLUS, 88 (90%) used
      it on 3136 occasions during an 18-month test period. CONCLUSIONS: This
      demonstration project shows the feasibility and use of a post-publication
      clinical peer review system that differentiates published journal articles
      according to the interests of a broad range of clinical disciplines.

PMID- 16622143
TI  - Birth spacing and risk of adverse perinatal outcomes: a meta-analysis.
AB  - CONTEXT: Both short and long interpregnancy intervals have been associated with
      an increased risk of adverse perinatal outcomes. However, whether this possible
      association is confounded by maternal characteristics or socioeconomic status is
      uncertain. OBJECTIVE: To examine the association between birth spacing and
      relative risk of adverse perinatal outcomes. DATA SOURCES: Studies published in
      any language were retrieved by searching MEDLINE (1966 through January 2006),
      EMBASE, ECLA, POPLINE, CINAHL, and LILACS, proceedings of meetings on birth
      spacing, and bibliographies of retrieved articles, and by contact with relevant
      researchers in the field. STUDY SELECTION: Included studies were cohort, cross
      sectional, and case-control studies with results adjusted for at least maternal
      age and socioeconomic status, reporting risk estimates and 95% confidence
      intervals (or data to calculate them) of birth spacing and perinatal outcomes. Of
      130 articles identified in the search, 67 (52%) were included. DATA EXTRACTION:
      Information on study design, participant characteristics, measure of birth
      spacing used, measures of outcome, control for potential confounding factors, and
      risk estimates was abstracted independently by 2 investigators using a
      standardized protocol. DATA SYNTHESIS: A random-effects model and meta-regression
      analyses were used to pool data from individual studies. Compared with
      interpregnancy intervals of 18 to 23 months, interpregnancy intervals shorter
      than 6 months were associated with increased risks of preterm birth, low birth
      weight, and small for gestational age (pooled adjusted odds ratios [95%
      confidence intervals]: 1.40 [1.24-1.58], 1.61 [1.39-1.86], and 1.26 [1.18-1.33],
      respectively). Intervals of 6 to 17 months and longer than 59 months were also
      associated with a significantly greater risk for the 3 adverse perinatal
      outcomes. CONCLUSIONS: Interpregnancy intervals shorter than 18 months and longer
      than 59 months are significantly associated with increased risk of adverse
      perinatal outcomes. These data suggest that spacing pregnancies appropriately
      could help prevent such adverse perinatal outcomes.

PMID- 16622144
TI  - The influence of estrogen on migraine: a systematic review.
AB  - CONTEXT: Menstrual migraine affects approximately 50% to 60% of female
      migraineurs, but knowledge regarding the role of hormones, especially estrogen,
      appears incomplete. OBJECTIVE: To conduct a systematic review to determine the
      role of hormones on menstrual migraine. EVIDENCE ACQUISITION: MEDLINE (January
      1966 through September 1, 2005) and EMBASE Drugs and Pharmacology (January 1991
      through September 1, 2005) were searched for articles published in the English
      language using the keywords migraine, estrogen, menstrual migraine, pure
      menstrual migraine, true menstrual migraine, menstrually-associated migraine,
      menstrually-related migraine, pregnancy, breast-feeding, perimenopause,
      menopause, nitric oxide, and estrogen receptors. A total of 643 unique articles
      were reviewed for relevance, scientific rigor, and generalizability. For each
      relevant citation, the bibliography was reviewed to identify additional sources
      of pertinent data. EVIDENCE SYNTHESIS: The influence of estrogen on migraine is
      evident by a 3-fold greater prevalence among women compared with men, and by
      significant changes in migraine incidence with changes in female reproductive
      status. Menstrual migraines are usually more resistant to treatment, generally
      not associated with aura, of longer duration, and associated with more functional
      disability compared with attacks at other times of the month. Biochemical and
      genetic evidence suggest central and peripheral roles for estrogen in the
      pathophysiology of menstrual migraine, with potential interactions with
      excitatory circuits, including serotonergic components. Although evidence for
      estrogen as a preventive treatment for menstrual migraine is inconsistent,
      serotonin receptor agonists (triptans) provide acute relief and also may have a
      role in prevention. CONCLUSIONS: Epidemiological, pathophysiological, and
      clinical evidence link estrogen to migraine headaches. Triptans appear to provide
      acute relief and also may be useful for headache prevention. Clear, focused, and
      evidence-based treatment algorithms are needed to support primary care
      physicians, neurologists, and gynecologists in the treatment of this common
      condition.

PMID- 16622145
TI  - Will physician-level measures of clinical performance be used in medical
      malpractice litigation?

PMID- 16622146
TI  - Mercury in dental amalgam--a neurotoxic risk?

PMID- 16622147
TI  - Birth spacing--the long and short of it.

PMID- 16622154
TI  - JAMA patient page. Medical journals.

PMID- 16622155
TI  - Performance of drug-drug interaction software for personal digital assistants.
AB  - BACKGROUND: Personal digital assistants (PDAs) allow healthcare professionals to
      check for potential drug-drug interactions (DDIs) at the point of care, reducing
      the need to consult traditional references. However, PDAs can only be as
      effective as the software programs they use. OBJECTIVE: To examine the ability of
      DDI software programs manufactured for Palm OS-compatible PDAs in detecting
      clinically important DDIs. METHODS: Eight PDA software programs were assessed for
      sensitivity, specificity, and positive and negative predictive values for 16 well
      documented DDIs contained within 6 simulated patient profiles. RESULTS:
      Sensitivity of the software programs ranged from 0.81 to 1.0, specificity ranged
      from 0.52 to 1.0, positive predictive values ranged from 0.62 to 1.0, and
      negative predictive values ranged from 0.88 to 1.0. Five programs scored perfect
      sensitivity scores: DrugIx, ePocrates Rx, ePocrates Rx Pro, Lexi-Interact, and
      the Tarascon pocket Pharmacopoeia. Of these, the ePocrates programs scored the
      highest in specificity (0.9), while Lexi-Interact and the Tarascon pocket
      Pharmacopoeia scored considerably lower (0.52). MosbyIx was the only program to
      score a 1.0 in specificity; however, its sensitivity was just 0.81. CONCLUSIONS:
      ePocrates Rx and ePocrates Rx Pro scored greater than or equal to 90% in regard
      to both sensitivity and specificity, making them the most reliable in detecting
      the clinically relevant interactions studied without the distraction of detecting
      those of no clinical significance. In addition, ePocrates Rx is updated regularly
      and is easily accessible on the Internet at no cost.

PMID- 16622156
TI  - Antioxidants, supplements, and Parkinson's disease.
AB  - OBJECTIVE: To review the use of antioxidants and other supplements for the
      prevention and treatment of Parkinson's disease (PD). DATA SOURCES: Biomedical
      literature was accessed through MEDLINE (1996-June 2005); key search terms
      included Parkinson's disease, coenzyme Q10 (CoQ10), antioxidants, supplements,
      and glutathione. Pertinent references cited in those articles were also evaluated
      for inclusion in this review. DATA SYNTHESIS: Three main antioxidants or
      supplements have been studied for use in the prevention or treatment of PD:
      tocopherol, CoQ10, and glutathione. These agents have been studied because of
      their potential to alter the course of 2 common theories of PD pathogenesis: free
      radical generation and mitochondrial complex-1 deficiency. The literature search
      revealed 3 large clinical studies of tocopherol (2 observational, 1 prospective
      randomized), 4 trials of CoQ10, and 1 study of glutathione. With the exception of
      the large observational studies with tocopherol and one study of CoQ10 that
      enrolled 80 patients, each of the other studies retrieved included fewer than 30
      patients and were conducted for 3 months or less. Antioxidant supplementation, in
      particular tocopherol, did not appear to alter the course of PD. However, in 2 of
      the studies of CoQ10 and in the study of glutathione, a small but statistically
      significant improvement in PD symptoms was observed. CONCLUSIONS: At present,
      antioxidants and supplements appear to have a limited role in the prevention or
      treatment of PD. Of those reviewed here, CoQ10 appears to provide some minor
      treatment benefits. More study is necessary to determine whether CoQ10 has a
      significant role as primary or adjunctive therapy in PD.

PMID- 16622157
TI  - Piperacillin/tazobactam-induced paresthesiae.
AB  - OBJECTIVE: To describe a case of a delayed-type hypersensitivity (DTH) reaction
      to piperacillin/tazobactam in which painful paresthesiae were a predominant
      feature. CASE SUMMARY: A 27-year-old man with a history of intravenous drug abuse
      was admitted for treatment of a pulmonary parenchymal abscess in the setting of
      lower-limb deep-venous thrombosis and methicillin-sensitive Staphylococcus aureus
      bacteremia. He was treated with intravenous piperacillin/tazobactam 4.5 g 3 times
      daily; however, after 2 weeks of therapy, he developed symptoms (eg, fever,
      chills) and laboratory abnormalities (eg, white blood cell count 2.1 x 10(3)/mm3,
      erythrocyte sedimentation rate 63 mm/h) suggestive of a DTH reaction. This was
      accompanied by infusion-related painful paresthesiae. The symptoms and laboratory
      abnormalities resolved within 48 hours of treatment being switched to
      flucloxacillin. DISCUSSION: Due to the close temporal association and the absence
      of any other obvious explanation, we believe these paresthesiae represent an
      additional feature of the DTH reaction to piperacillin/tazobactam in this
      patient. Use of the Naranjo probability scale indicated a probable relationship
      between the paresthesiae and administration of piperacillin/tazobactam.
      CONCLUSIONS: To our knowledge, as of March 24, 2006, this is the first case in
      which a DTH reaction to piperacillin/tazobactam manifesting as fever,
      neutropenia, and thrombocytopenia has been associated with paresthesiae.

PMID- 16622158
TI  - Use of sildenafil for female sexual dysfunction.
AB  - OBJECTIVE: To review the pathophysiology of female sexual dysfunction (FSD) and
      the literature regarding the use of sildenafil in its treatment. DATA SOURCES:
      Literature was accessed through MEDLINE (1966-April 2006), Iowa Drug Information
      Service (1966-April 2006), EMBASE (1966-April 2006), and bibliographies of
      pertinent articles. Search terms included female sexual dysfunction; sexual
      dysfunction, psychological; phosphodiesterase inhibitors; and sildenafil. DATA
      SYNTHESIS: The lack of a clear understanding of FSD contributes to the limited
      treatment options available. Studies regarding the safety and efficacy of the
      phosphodiesterase 5 inhibitor sildenafil in the management of FSD were evaluated.
      Many trials have been of poor quality, making clinical application of their
      results difficult. The current literature does not show sildenafil to be an
      effective treatment option for FSD. CONCLUSIONS: Treatment of FSD should include
      both physical and psychological components. Based on the limited data available,
      it appears that sildenafil, while well tolerated, offers little or no benefit to
      most patients with FSD.

PMID- 16622159
TI  - Automated surveillance for adverse drug events at a community hospital and an
      academic medical center.
AB  - OBJECTIVES: To compare the rates and nature of ADEs at an academic medical center
      and a community hospital using a single computerized ADE surveillance system.
      DESIGN: Prospective cohort study of patients admitted to two tertiary care
      hospitals. Outcome Measure Adverse drug events identified by automated
      surveillance and voluntary reporting. METHODS: We implemented an automated
      surveillance system across an academic medical center and a community hospital.
      Potential events identified by the computer were reviewed in detail by medication
      safety pharmacists and scored for causality and severity. Findings were compared
      between the two hospitals, and with voluntary reports from nurses and
      pharmacists. RESULTS: Over the 8 month study period, 25,177 patients were
      admitted to the university hospital and 8,029 to the community hospital. There
      were 1,116 ADEs in 900 patients at the university hospital for an overall rate of
      4.4 ADEs per 100 admissions. At the community hospital, 399 patients experienced
      501 ADEs for a rate of 6.2 events per 100 admissions. Rates of antibiotic
      associated colitis, drug-induced hypoglycemia, and anticoagulation-related ADEs
      were significantly higher at the community hospital compared with the university
      hospital. Computerized surveillance detected ADEs at a rate 3.6 times that of
      voluntary reporting at the university hospital and 12.3 times that at the
      community hospital. CONCLUSIONS: Operation of a common automated ADE surveillance
      system across hospitals permits meaningful comparison of ADE rates in different
      inpatient settings. Automated surveillance detects ADEs at rates far higher than
      voluntary reporting, and the difference may be greater in the community hospital
      setting. Community hospitals may experience higher rates of certain types of ADEs
      compared with academic medical centers.

PMID- 16622160
TI  - Using commercial knowledge bases for clinical decision support: opportunities,
      hurdles, and recommendations.

PMID- 16622161
TI  - An informatics blueprint for healthcare quality information systems.
AB  - There is a critical gap in our nation's ability to accurately measure and manage
      the quality of medical care. A robust healthcare quality information system
      (HQIS) has the potential to address this deficiency through the capture,
      codification, and analysis of information about patient treatments and related
      outcomes. Because non-technical issues often present the greatest challenges,
      this paper provides an overview of these socio-technical issues in building a
      successful HQIS, including the human, organizational, and knowledge management
      (KM) perspectives. Through an extensive literature review and direct experience
      in building a practical HQIS (the National Comprehensive Cancer Network Outcomes
      Research Database system), we have formulated an "informatics blueprint" to guide
      the development of such systems. While the blueprint was developed to facilitate
      healthcare quality information collection, management, analysis, and reporting,
      the concepts and advice provided may be extensible to the development of other
      types of clinical research information systems.

PMID- 16622162
TI  - Impact of a computerized clinical decision support system on reducing
      inappropriate antimicrobial use: a randomized controlled trial.
AB  - OBJECTIVE: Many hospitals utilize antimicrobial management teams (AMTs) to
      improve patient care. However, most function with minimal computer support. We
      evaluated the effectiveness and cost-effectiveness of a computerized clinical
      decision support system for the management of antimicrobial utilization. DESIGN:
      A randomized controlled trial in adult inpatients between May 10 and August 3,
      2004. Antimicrobial utilization was managed by an existing AMT using the system
      in the intervention arm and without the system in the control arm. The system was
      developed to alert the AMT of potentially inadequate antimicrobial therapy.
      MEASUREMENTS: Outcomes assessed were hospital antimicrobial expenditures,
      mortality, length of hospitalization, and time spent managing antimicrobial
      utilization. RESULTS: The AMT intervened on 359 (16%) of 2,237 patients in the
      intervention arm and 180 (8%) of 2,270 in the control arm, while spending
      approximately one hour less each day on the intervention arm. Hospital
      antimicrobial expenditures were $285,812 in the intervention arm and $370,006 in
      the control arm, for a savings of $84,194 (23%), or $37.64 per patient. No
      significant difference was observed in mortality (3.26% vs. 2.95%, p = 0.55) or
      length of hospitalization (3.84 vs. 3.99 days, p = 0.38). CONCLUSION: Use of the
      system facilitated the management of antimicrobial utilization by allowing the
      AMT to intervene on more patients receiving inadequate antimicrobial therapy and
      to achieve substantial time and cost savings for the hospital. This is the first
      study that demonstrates in a patient-randomized controlled trial that
      computerized clinical decision support systems can improve existing antimicrobial
      management programs.

PMID- 16622163
TI  - Disseminating drug prescribing information: the cox-2 inhibitors withdrawals.
AB  - This case study examined the recent withdrawal of valdecoxib to determine the
      timeliness of updates in commonly used information sources used by healthcare
      professionals. The method included assembling a purposive sample of 15 drug
      reference and warning systems that were then systematically monitored for several
      months after the withdrawal of valdecoxib to determine the time to update this
      information. These information sources were classified and described
      qualitatively. A time to diffusion curve was plotted and the average number of
      days to report the drug withdrawal or update reference databases was calculated.
      Only 2 of 15 information systems reported the drug withdrawal on the actual date
      of the FDA announcement. Institutional electronic textbooks took an average of
      109.8 days (+/-14 days) to report the withdrawal. In addition, one pharma
      sponsored dissemination source (Peerview Press) had not updated their information
      as of this publication.

PMID- 16622164
TI  - Biomedical informatics applications for asthma care: a systematic review.
AB  - Asthma is a common condition associated with significant patient morbidity and
      health care costs. Although widely accepted evidence-based guidelines for asthma
      management exist, unnecessary variation in patient care remains. Application of
      biomedical informatics techniques is one potential way to improve care for
      asthmatic patients. We performed a systematic literature review to identify
      computerized applications for clinical asthma care. Studies were evaluated for
      their clinical domain, developmental stage and study design. Additionally,
      prospective trials were identified and analyzed for potential study biases, study
      effects, and clinical study characteristics. Sixty-four papers were selected for
      review. Publications described asthma detection or diagnosis (18 papers), asthma
      monitoring or prevention (13 papers), patient education (13 papers), and asthma
      guidelines or therapy (20 papers). The majority of publications described
      projects in early stages of development or with non-prospective study designs.
      Twenty-one prospective trials were identified, which evaluated both clinical and
      non-clinical impacts on patient care. Most studies took place in the outpatient
      clinic environment, with minimal study of the emergency department or inpatient
      settings. Few studies demonstrated evidence of computerized applications
      improving clinical outcomes. Further research is needed to prospectively evaluate
      the impact of using biomedical informatics to improve care of asthmatic patients.

PMID- 16622165
TI  - A comparison of citation metrics to machine learning filters for the
      identification of high quality MEDLINE documents.
AB  - OBJECTIVE: The present study explores the discriminatory performance of existing
      and novel gold-standard-specific machine learning (GSS-ML) focused filter models
      (i.e., models built specifically for a retrieval task and a gold standard against
      which they are evaluated) and compares their performance to citation count and
      impact factors, and non-specific machine learning (NS-ML) models (i.e., models
      built for a different task and/or different gold standard). DESIGN: Three gold
      standard corpora were constructed using the SSOAB bibliography, the ACPJ-cited
      treatment articles, and the ACPJ-cited etiology articles. Citation counts and
      impact factors were obtained for each article. Support vector machine models were
      used to classify the articles using combinations of content, impact factors, and
      citation counts as predictors. MEASUREMENTS: Discriminatory performance was
      estimated using the area under the receiver operating characteristic curve and n
      fold cross-validation. RESULTS: For all three gold standards and tasks, GSS-ML
      filters outperformed citation count, impact factors, and NS-ML filters.
      Combinations of content with impact factor or citation count produced no or
      negligible improvements to the GSS machine learning filters. CONCLUSIONS: These
      experiments provide evidence that when building information retrieval filters
      focused on a retrieval task and corresponding gold standard, the filter models
      have to be built specifically for this task and gold standard. Under those
      conditions, machine learning filters outperform standard citation metrics.
      Furthermore, citation counts and impact factors add marginal value to
      discriminatory performance. Previous research that claimed better performance of
      citation metrics than machine learning in one of the corpora examined here is
      attributed to using machine learning filters built for a different gold standard
      and task.

PMID- 16622166
TI  - Defining obtrusiveness in home telehealth technologies: a conceptual framework.
AB  - The literature of home telehealth technology recommends that systems be designed
      to minimize their obtrusiveness to end users. However, this term is neither
      explicitly defined nor consistently used. This paper presents a definition of the
      concept of obtrusiveness. Within this definition, twenty-two categories of what
      may be perceived as obtrusive in home telehealth technology are proposed based on
      a review of the literature. These categories are grouped into eight dimensions.
      This effort represents an initial step toward developing measures of
      obtrusiveness associated with home telehealth technology. A validated and
      reliable instrument would allow for evaluation of individual applications as well
      as theory-building across applications.

PMID- 16622167
TI  - ResourceLog: an embeddable tool for dynamically monitoring the usage of web-based
      bioscience resources.
AB  - The present study described an open source application, ResourceLog, that allows
      website administrators to record and analyze the usage of online resources. The
      application includes four components: logging, data mining, administrative
      interface, and back-end database. The logging component is embedded in the host
      website. It extracts and streamlines information about the Web visitors, the
      scripts, and dynamic parameters from each page request. The data mining component
      runs as a set of scheduled tasks that identify visitors of interest, such as
      those who have heavily used the resources. The identified visitors will be
      automatically subjected to a voluntary user survey. The usage of the website
      content can be monitored through the administrative interface and subjected to
      statistical analyses. As a pilot project, ResourceLog has been implemented in
      SenseLab, a Web-based neuroscience database system. ResourceLog provides a robust
      and useful tool to aid system evaluation of a resource-driven Web application,
      with a focus on determining the effectiveness of data sharing in the field and
      with the general public.

PMID- 16622168
TI  - Case report: activity diagrams for integrating electronic prescribing tools into
      clinical workflow.
AB  - To facilitate the future implementation of an electronic prescribing system, this
      case study modeled prescription management processes in various primary care
      settings. The Vanderbilt e-prescribing design team conducted initial interviews
      with clinic managers, physicians and nurses, and then represented the sequences
      of steps carried out to complete prescriptions in activity diagrams. The diagrams
      covered outpatient prescribing for patients during a clinic visit and between
      clinic visits. Practice size, practice setting, and practice specialty type
      influenced the prescribing processes used. The model developed may be useful to
      others engaged in building or tailoring an e-prescribing system to meet the
      specific workflows of various clinic settings.

PMID- 16622169
TI  - Managing the life cycle of electronic clinical documents.
AB  - OBJECTIVE: To develop a model of the life cycle of clinical documents from
      inception to use in a person's medical record, including workflow requirements
      from clinical practice, local policy, and regulation. DESIGN: We propose a model
      for the life cycle of clinical documents as a framework for research on
      documentation within electronic medical record (EMR) systems. Our proposed model
      includes three axes: the stages of the document, the roles of those involved with
      the document, and the actions those involved may take on the document at each
      stage. The model includes the rules to describe who (in what role) can perform
      what actions on the document, and at what stages they can perform them. Rules are
      derived from needs of clinicians, and requirements of hospital bylaws and
      regulators. RESULTS: Our model encompasses current practices for paper medical
      records and workflow in some EMR systems. Commercial EMR systems include methods
      for implementing document workflow rules. Workflow rules that are part of this
      model mirror functionality in the Department of Veterans Affairs (VA) EMR system
      where the Authorization/ Subscription Utility permits document life cycle rules
      to be written in English-like fashion. CONCLUSIONS: Creating a model of the life
      cycle of clinical documents serves as a framework for discussion of document
      workflow, how rules governing workflow can be implemented in EMR systems, and
      future research of electronic documentation.

PMID- 16622170
TI  - Evaluation of the expressiveness of an ICNP-based nursing data dictionary in a
      computerized nursing record system.
AB  - This study evaluated the domain completeness and expressiveness issues of the
      International Classification for Nursing Practice-based (ICNP) nursing data
      dictionary (NDD) through its application in an enterprise electronic medical
      record (EMR) system as a standard vocabulary at a single tertiary hospital in
      Korea. Data from 2,262 inpatients obtained over a period of 9 weeks (May to July
      2003) were extracted from the EMR system for analysis. Among the 530,218 data
      input events, 401,190 (75.7%) were entered from the NDD, 20,550 (3.9%) used only
      free text, and 108,478 (20.4%) used a combination of coded data and free text. A
      content analysis of the free-text events showed that 80.3% of the expressions
      could be found in the NDD, whereas 10.9% were context-specific expressions such
      as direct quotations of patient complaints and responses, and references to the
      care plan or orders of physicians. A total of 7.8% of the expressions was used
      for a supplementary purpose such as adding a conjunction or end verb to make an
      expression appear as natural language. Only 1.0% of the expressions were
      identified as not being covered by the NDD. This evaluation study demonstrates
      that the ICNP-based NDD has sufficient power to cover most of the expressions
      used in a clinical nursing setting.

PMID- 16622171
TI  - Prescribers' responses to alerts during medication ordering in the long term care
      setting.
AB  - OBJECTIVE: Computerized physician order entry with clinical decision support has
      been shown to improve medication safety in adult inpatients, but few data are
      available regarding its usefulness in the long-term care setting. The objective
      of this study was to examine opportunities for improving medication safety in
      that clinical setting by determining the proportion of medication orders that
      would generate a warning message to the prescriber via a computerized clinical
      decision support system and assessing the extent to which these alerts would
      affect prescribers' actions. DESIGN: The study was set within a randomized
      controlled trial of computerized clinical decision support conducted in the long
      stay units of a large, academically-affiliated long-term care facility. In March
      2002, a computer-based clinical decision support system (CDSS) was added to an
      existing computerized physician order entry (CPOE) system. Over a subsequent one
      year study period, prescribers ordering drugs for residents on three resident
      care units of the facility were presented with alerts; these alerts were not
      displayed to prescribers in the four control units. MEASUREMENTS: We assessed the
      frequency of drug orders associated with various categories of alerts across all
      participating units of the facility. To assess the impact of actually receiving
      an alert on prescriber behavior during drug ordering, we calculated separately
      for the intervention and control units the proportion of the alerts, within each
      category, that were followed by an appropriate action and estimated the relative
      risk of an appropriate action in the intervention units compared to the control
      units. RESULTS: During the 12 months of the study, there were 445 residents on
      the participating units of the facility, contributing 3,726 resident-months of
      observation time. During this period, 47,997 medication orders were entered
      through the CPOE system-approximately 9 medication orders per resident per month.
      9,414 alerts were triggered (2.5 alerts per resident-month). The alert categories
      most often triggered were related to risks of central nervous system side-effects
      such as over-sedation (20%). Alerts for risk of drug-associated constipation
      (13%) or renal insufficiency/electrolyte imbalance (12%) were also common. Twelve
      percent of the alerts were related to orders for warfarin. Overall, prescribers
      who received alerts were only slightly more likely to take an appropriate action
      (relative risk 1.11, 95% confidence interval 1.00, 1.22). Alerts related to
      orders for warfarin or central nervous system side effects were most likely to
      engender an appropriate action, such as ordering a recommended laboratory test or
      canceling an ordered drug. CONCLUSION: Long-term care facilities must implement
      new system-level approaches with the potential to improve medication safety for
      their residents. The number of medication orders that triggered a warning message
      in this study suggests that CPOE with a clinical decision support system may
      represent one such tool. However, the relatively low rate of response to these
      alerts suggests that further refinements to such systems are required, and that
      their impact on medication errors and adverse drug events must be carefully
      assessed.

PMID- 16622172
TI  - Caspases and calpain are independent mediators of cisplatin-induced endothelial
      cell necrosis.
AB  - The role of caspases and calpain in cisplatin-induced endothelial cell death is
      unknown. Thus we investigated whether caspases and calpain are mediators of
      cisplatin-induced apoptosis and necrosis in endothelial cells. Cultured
      pancreatic microvascular endothelial (MS1) cells were exposed to 10 and 50 microM
      cisplatin. Apoptosis or necrosis was determined by Hoechst 33342 and propidium
      iodide (PI) nuclear staining. Cells treated with 10 microM cisplatin had normal
      ATP levels, increased caspase-3-like activity, excluded PI and demonstrated
      morphological characteristics of apoptosis at 24 h. Cells treated with 50 microM
      cisplatin had severe ATP depletion, increased caspase-3-like activity, and
      displayed extensive PI staining indicative of necrosis at 24 h. There was a dose
      dependent increase in caspase-2-like activity and Smac/DIABLO protein. Calpain
      activity increased significantly with 50 microM, but not 10 microM cisplatin at
      24 h. With 50 microM cisplatin, ATP levels were significantly reduced starting at
      18 h, caspase-2- and caspase-3-like activities were significantly increased
      starting at 18 h, and LDH release started at 8 h with maximum increase at 18-24
      h. Calpain activity was not increased before 24 h. The increase in LDH release
      and the nuclear PI staining with 50 microM cisplatin at 24 h was reduced by
      either the pancaspase inhibitor, Q-VD-OPH, or the calpain inhibitor, PD-150606.
      Calpain inhibitor had no effect on caspase-3-like activity. In conclusion, in
      cisplatin-treated endothelial cells, caspases, the major mediators of apoptosis,
      can also cause necrosis. A calpain inhibitor protects against necrosis without
      affecting caspase-3-like activity suggesting that calpain-mediated necrosis is
      independent of caspase-3.

PMID- 16622173
TI  - Podocyte proteoglycan synthesis is involved in the development of nephrotic
      syndrome.
AB  - Proteoglycans (PGs) are important for the glomerular barrier, for cell signaling,
      and for the anchorage of cells to the glomerular basement membrane. They are,
      however, complex macromolecules, and their production has not yet been thoroughly
      investigated in podocytes. In the present study, we studied the biosynthesis of
      PGs by highly differentiated human podocytes and in rats. The cells were treated
      with puromycin aminonucleoside (PAN; a nephrosis-inducing agent), steroids (used
      as primary treatment for nephrotic syndrome), or both. Analysis was made by
      TaqMan real-time PCR, Western blotting, and by metabolic labeling with (35)S and
      (3)H. We found that podocytes produce versican, syndecan-1, decorin, and biglycan
      together with the previously known PG syndecan-4, glypican, and perlecan. PAN
      treatment downregulated the mRNA and the protein expression of both versican (by
      24 +/- 6%, P < 0.01, for mRNA and by 50% for protein) and perlecan (by 14 +/- 5%,
      P < 0.05, for mRNA and by 50% for protein). The decreased expression was
      confirmed by studying the glomerular gene expression in rats treated with PAN
      during a time course study. In addition, puromycin decreased the expression of
      enzymes involved in the glycosaminoglycan biosynthesis. Steroid treatment
      decreased perlecan (by 24 +/- 3%, P < 0.01) and syndecan-1 expression (by 30 +/-
      4%, P < 0.01) but increased the expression of decorin 2.5-fold. The observed
      alterations of PG synthesis induced by PAN may lead to decreased glomerular
      anionic charge and disturbed podocyte morphology, factors that are important for
      the development of a nephrotic syndrome.

PMID- 16622174
TI  - Epithelial cell polarity and hypoxia influence heme oxygenase-1 expression by
      heme in renal epithelial cells.
AB  - Induction of heme oxygenase-1 (HO-1) in renal tubules occurs as an adaptive and
      beneficial response in acute renal failure (ARF) following ischemia and
      nephrotoxins. Using an in vitro model of polarized Madin-Darby canine kidney
      (MDCK) epithelial cells, we examined apical and basolateral cell surface
      sensitivity to HO-1 induction by heme. Basolateral exposure to 5 microM hemin
      (heme chloride) resulted in higher HO-1 induction than did apical exposure. The
      peak induction of HO-1 by basolateral application of hemin occurred between 12
      and 18 h of exposure and was dose dependent. Similar cell surface sensitivity to
      hemin-induced HO-1 expression was observed using a mouse cortical collecting duct
      cell line (94D cells). Hepatocyte growth factor (HGF) is known to decrease cell
      polarity of MDCK cells. Following pretreatment with HGF, apically applied hemin
      gave greater stimulation of HO-1 expression, whereas HGF alone did not induce HO
      1. We also examined the effect of hypoxia on hemin-mediated HO-1 induction. MDCK
      cells were subjected to hypoxia (1% O(2)) for 24 h to simulate the effects of
      ischemic ARF. Under hypoxic conditions, both apical as well as basolateral
      surfaces of MDCK were more sensitive to HO-1 induction by hemin. Hypoxia alone
      did not induce HO-1 but appeared to potentiate both apical and basolateral
      sensitivity to hemin-mediated induction. These data demonstrate that the
      induction of HO-1 expression in polarized renal epithelia by heme is achieved
      primarily via basolateral exposure. However, under conditions of altered renal
      epithelial cell polarity and hypoxia, increased HO-1 induction occurs following
      apical exposure to heme.

PMID- 16622175
TI  - Mesenchymal cells from adult kidney support angiogenesis and differentiate into
      multiple interstitial cell types including erythropoietin-producing fibroblasts.
AB  - Mesenchymal cells have been isolated from embryos and multiple adult organs where
      they may differentiate into various connective tissue cell types and provide
      paracrine support for surrounding cells. With the use of a technique for
      culturing multipotent mesenchymal cells from adult tissues, a fibroblast-like
      cell clone (4E) was isolated from adult mouse kidney. 4E cells were able to
      differentiate along multiple mesodermal lineages including cell types located in
      the renal interstitium such as fibroblasts and pericytes. Coculture of 4E cells
      with ureteric bud and epithelial cell lines and analysis of resulting changes in
      gene expression revealed that these cells support angiogenesis and tubulogenesis
      and expressed genes characteristic of embryonic renal stromal cells. Following
      subcapsular injection after unilateral ischemia-reperfusion in adult mice, 4E
      cells migrated to a peritubular interstitial location and expressed interstitial
      cell markers, whereas cells injected in control kidneys remained stationary.
      Incubation in hypoxic or anoxic conditions resulted in erythropoietin expression
      in a small subset of ecto-5'-nucleotidase-positive cells and resulted in
      increased vascular endothelial growth factor expression in the same cell
      population. Our findings suggest that the adult kidney may contain interstitial
      mesenchymal cell progenitors with embryonic stromal cell characteristics that are
      able to provide paracrine support for surrounding vessels and tubular epithelial
      cells and differentiate into erythropoietin producing fibroblasts.

PMID- 16622176
TI  - Urine protein markers distinguish stone-forming from non-stone-forming relatives
      of calcium stone formers.
AB  - We have investigated urine protein inhibitors of calcium oxalate crystallization
      to determine whether variations in these proteins are associated with kidney
      stone disease and whether protein measurements improve the identification of
      stone formers compared with conventional risk factors (RF). Using Western
      blotting, we studied variations in the electrophoretic mobility patterns and
      relative abundances of crystallization-inhibitory proteins in urine from 50 stone
      forming (SF) and 50 non-stone-forming (NS) first-degree relatives of calcium SF
      patients, matched by gender and age. Standard urine chemistry stone risk
      measurements were also made. Multivariate discriminant analysis was used to test
      the association of these proteins with nephrolithiasis. Differences in form and
      abundance of several urine proteins including inter-alpha-trypsin inhibitor
      (ITI), prothrombin fragment 1 (PF1), CD59, and calgranulin B (calB) were found to
      be associated with stone formation. By multivariate discriminant analysis,
      measurements of forms of PF1, ITI, and calB in men and ITI and CD59 in women,
      classified 84% of men and 76% of women correctly by stone status. In contrast,
      standard urine chemistry RF identified only 70% of men correctly and failed to
      distinguish female SF from NS. Thus a small subset of protein measurements
      distinguished SF from NS far better than conventional RF in a population of
      relatives of calcium SF, illustrating the significant association of these
      proteins with stone disease. Variations in these proteins may serve as markers of
      stone disease activity or vulnerability to recurrence and may provide new
      insights into mechanisms of stone formation.

PMID- 16622177
TI  - Role of NH(2) and COOH termini in targeting, stability, and activity of sodium
      bicarbonate cotransporter 1.
AB  - Sodium bicarbonate cotransporter 1 (NBC1) mediates 80% of bicarbonate
      reabsorption by the kidney, but the molecular determinants for activity,
      targeting, and cell membrane stability are poorly understood. We generated
      truncation mutants involving the entire NH(2) (DeltaN424) or the entire COOH
      (DeltaC92) terminus and examined the effects of these truncations on targeting,
      cell membrane stability, and NBC1 activity. DeltaN424 and DeltaC92 targeted to
      the plasma membrane of HEK293 cells or to the basolateral membrane of opossum
      kidney (OK) cells at 24 h but did not display NBC1 activity. Unlike the NBC1 wild
      type and the DeltaN424, DeltaC92 expression was significantly decreased in the
      basolateral membrane at 48 h and yet the total DeltaC92 expression in the cell
      was constant. We found that decreased DeltaC92 expression in the basolateral
      membrane was due to increased endocytosis and mistargeting to the apical
      membrane. Increased endocytosis was prevented when both DeltaN424 and DeltaC92
      were cotransfected together and more stable expression of DeltaC92 was observed.
      Immunoprecipitation studies using NBC1 antibody specific for the COOH epitope
      were able to detect the COOH truncated NBC1 when probed with NH(2) epitope
      specific antibody or vice versa. Similar findings were observed with Ni-NTA pull
      down assay. Cotransfection of both mutants partially restored NBC1 activity. In
      summary, NBC1 targets to the basolateral membrane of OK cells by a default
      mechanism and the COOH terminus plays a role on NBC1 stability in the basolateral
      membrane.

PMID- 16622178
TI  - Upregulation of Id-1 via BMP-2 receptors induces reactive oxygen species in
      podocytes.
AB  - Bone morphogenetic proteins (BMPs) are secreted signaling molecules, which play a
      major role in kidney development and disease. Here, we show the existence of mRNA
      for BMP-2 and for the BMP receptors BMPR1A, BMPR1B, BMPRII, ACVR1A, ACVR2, and
      ACVR2B in differentiated mouse podocytes and the protein expression of BMPR1A in
      human glomerular podocytes. BMP-2 dose dependently increases the free cytosolic
      Ca(2+) concentration in podocytes proving the existence of a functional receptor
      in these cells. Recent data indicate that in a myoblastic cell line and in a
      breast cancer cell line, BMP-2 increases the expression of Id-1, a negative
      regulator of basic helix-loop-helix transcription factors, but the role of BMP-2
      stimulated Id-1 expression in the kidney has not been further characterized.
      Here, we show that BMP-2 increases the expression of Id-1 in differentiated
      podocytes. To investigate a role of Id-1 for podocyte function, overexpression of
      Id-1 was induced in differentiated mouse podocytes. Id-1-overexpressing podocytes
      show an increased NADPH-dependent production of reactive oxygen species (ROS).
      This effect can be evoked by BMP-2 and can be antagonized by anti-Id-1 antisense
      oligonucleotides. The data indicate that BMP-2 may, via an increased expression
      of Id-1 and an increased generation of ROS, contribute to important cellular
      functions in podocytes. ROS supposedly play a major role in cell adhesion, cell
      injury, ion transport, fibrogenesis, angiogenesis and are involved in the
      pathogenesis of membranous nephropathy.

PMID- 16622179
TI  - Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis.
AB  - Interstitial cystitis (IC) is a chronic bladder inflammatory disease of unknown
      etiology that shares similarities with Crohn's disease and psoriasis. IC, often
      regarded as a neurogenic cystitis, is associated with urothelial lesions that
      likely compromise the bladder permeability barrier and thereby contribute to
      patient morbidity. Here, we use a murine model of neurogenic cystitis to
      investigate the mechanism of urothelial lesion formation and find that urothelial
      apoptosis induces formation of lesions. Lesions formed in wild-type mice but not
      in mice deficient in TNF, TNF receptors, or mast cells. In urothelial cultures,
      only siRNAs targeting TNFR1, but not TNFR2, blocked TNF-induced apoptosis,
      indicating a primary role for TNFR1. Trans-epithelial resistance, a measure of
      bladder barrier function, decreased during neurogenic cystitis in wild-type and
      TNFR2(-/-) mice but was stabilized in TNF(-/-) mice. Anti-TNF antibodies both
      altered bladder mast cell localization and stabilized barrier function. Based on
      these findings, we conclude that mast cell activation and release of TNF drive
      urothelial apoptosis and lesion formation in a murine neurogenic cystitis model,
      and we hypothesize that anti-TNF therapy may stabilize bladder barrier function
      in IC patients.

PMID- 16622180
TI  - Glucose transporters in animal models of diabetes and hypertension.

PMID- 16622181
TI  - Cyclooxygenase-2 inhibition normalizes arterial blood pressure in CYP1A1-REN2
      transgenic rats with inducible ANG II-dependent malignant hypertension.
AB  - The present study was performed to determine the effects of cyclooxygenase (COX)
      1 and COX-2 inhibition on blood pressure and renal hemodynamics in transgenic
      rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male
      Cyp1a1-Ren2 rats (n = 7) were fed a normal diet containing the aryl hydrocarbon,
      indole-3-carbinol (I3C; 0.3%), for 6-9 days to induce malignant hypertension.
      Mean arterial pressure (MAP) and renal hemodynamics were measured in
      pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats during control conditions,
      following administration of the COX-2 inhibitor nimesulide (3 mg/kg iv), and
      following administration of the nonspecific COX inhibitor meclofenamate (5 mg/kg
      iv). Rats induced with I3C had higher MAP than noninduced rats (n = 7; 188 +/- 6
      vs. 136 +/- 4 mmHg, P < 0.01). There was no difference in renal plasma flow (RPF)
      or glomerular filtration rate (GFR) between induced and noninduced rats.
      Nimesulide elicited a larger decrease in MAP in hypertensive rats (188 +/- 6 to
      140 +/- 8 mmHg, P < 0.01) than in normotensive rats (136 +/- 4 to 113 +/- 8 mmHg,
      P < 0.01). Additionally, nimesulide decreased GFR (0.9 +/- 0.13 to 0.44 +/- 0.05
      ml.min(-1).g(-1), P < 0.05) and RPF (2.79 +/- 0.27 to 1.35 +/- 0.14 ml.min(-1).g(
      1), P < 0.05) in hypertensive rats but did not alter GFR or RPF in normotensive
      rats. Meclofenamate further decreased MAP in hypertensive rats (to 115 +/- 10
      mmHg, P < 0.05) but did not decrease MAP in normotensive rats. Meclofenamate did
      not alter GFR or RPF in either group. These findings demonstrate that COX-1- and
      COX-2-derived prostanoids contribute importantly to the development of malignant
      hypertension in Cyp1a1-Ren2 transgenic rats. The data also indicate that COX-2
      derived vasodilatory metabolites play an important role in the maintenance of RPF
      and GFR following induction of malignant hypertension in Cyp1a1-Ren2 transgenic
      rats.

PMID- 16622183
TI  - Rapid photoinactivation of native AMPA receptors on live cells using ANQX.
AB  - AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, a
      major subtype of ionotropic glutamate receptors, mediate the majority of fast
      excitatory synaptic transmission in the mammalian brain. The constitutive and
      regulated trafficking of AMPA receptors into and out of excitatory synapses
      ensures rapid responses to synaptically released glutamate and provides a
      mechanism for synaptic plasticity. To permit the direct, quantitative, real-time
      measurement of native AMPA receptor trafficking in live neurons, we designed and
      utilized a membrane-impermeable, photoreactive AMPA receptor antagonist to
      rapidly and irreversibly inactivate surface receptors with ultraviolet (UV)
      light. The photoreactive antagonist, 6-azido-7-nitro-1,4-dihydroquinoxaline-2,3
      dione (ANQX), is an aryl azide that, when irradiated with UV light, becomes a
      highly reactive nitrene that can covalently cross-link to and thus irreversibly
      antagonize bound AMPA receptors. Thus, ANQX provides a means of rapidly silencing
      surface-exposed AMPA receptors. Combined with a functional AMPA receptor assay,
      such as continuous recording of AMPA receptor-mediated ionic currents, ANQX
      provides a means of directly monitoring native AMPA receptor trafficking in real
      time.

PMID- 16622184
TI  - Fanciful FRET.
AB  - The validity of experiments based on Forster resonance energy transfer (FRET), an
      imaging technique widely used to measure protein-protein interactions in living
      cells, critically depends on the accurate and precise measurement of FRET
      efficiency. The use of FRET standards to determine FRET efficiency, and a
      consideration of such factors as how the abundance of FRET acceptors and the
      stoichiometry of donors and acceptors in a molecular complex can affect measured
      FRET efficiency, will enhance the usefulness with which FRET experiments can be
      interpreted.

PMID- 16622185
TI  - How the bacterial pathogen Listeria monocytogenes mediates the switch from
      environmental Dr. Jekyll to pathogenic Mr. Hyde.

PMID- 16622186
TI  - Bartonella henselae Pap31, an extracellular matrix adhesin, binds the fibronectin
      repeat III13 module.
AB  - Bartonella henselae wound-associated infections suggest involvement of
      extracellular matrix molecules in adhesion and invasion. Pap31 was previously
      identified as a hemin-binding protein. Our recent studies suggest the protein is
      an adhesin that is recognized by the host's immune systems. In this study we
      examined the interactions of B. henselae Pap31 with fibronectin (Fn), heparin
      (Hep), and human umbilical vein endothelial cells (HUVECs). The cloned gene was
      expressed in Escherichia coli, and the purified Pap31 protein elicited strong
      antibody responses in mice and was reactive with rabbit anti-live B. henselae and
      mouse anti-Pap31 antibodies by Western blotting. Pap31 bound to immobilized Fn
      and to HUVECs in a dose-dependent manner and to Hep. Fn fragment-binding assays
      identified the Hep-1 and Hep-2 binding domains of human Fn and in particular the
      (12-13)FnIII repeat module as primary binding sites for this adhesin.
      Furthermore, Pap31 binding to the above Fn fragments could be inhibited by Hep,
      suggesting a common binding site involving the 13FnIII repeat module on the Hep-2
      domain of Fn. Adherence of intact B. henselae to HUVECs was inhibited by
      increasing concentrations of anti-Pap31 antibodies. In addition, purified Pap31
      coprecipitated effectively with Fn and anti-Fn antibodies. Taken together, these
      data suggest that Pap31 is an Fn-binding protein mediating the B. henselae-host
      interaction(s), and they implicate the 13FnIII repeat module as an important
      binding site for this adhesin on the Fn molecule. These interactions may be
      important initial steps leading to bacterial attachment and colonization that
      promote the establishment of B. henselae infections in vivo.

PMID- 16622187
TI  - Toll-like receptor 4 contributes to colitis development but not to host defense
      during Citrobacter rodentium infection in mice.
AB  - Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are
      noninvasive bacterial pathogens that infect their hosts' intestinal epithelium,
      causing severe diarrheal disease. These infections also cause intestinal
      inflammation, although the mechanisms underlying the inflammatory response, as
      well as its potential role in host defense, are unclear. Since these bacteria are
      gram-negative, Toll-like receptor 4 (TLR4), the innate receptor for bacterial
      lipopolysaccharide may contribute to the host response; however, the role of TLR4
      in the gastrointestinal tract is poorly understood, and its impact has yet to be
      tested against this family of enteric bacterial pathogens. Since EPEC and EHEC
      are human specific, we infected mice with Citrobacter rodentium, a mouse-adapted
      attaching and effacing (A/E) bacterium that infects colonic epithelial cells,
      causing colitis and epithelial hyperplasia, using a similar array of virulence
      proteins as EPEC and EHEC. We demonstrated that C. rodentium activates TLR4 and
      rapidly induced NF-kappaB nuclear translocation in host cells in a partially TLR4
      dependent manner. Infection of TLR4-deficient mice revealed that TLR4-dependent
      responses mediate much of the inflammation and tissue pathology seen during
      infection, including the induction of the chemokines MIP-2 and MCP-1, as well as
      the recruitment of macrophages and neutrophils into the infected intestine.
      Surprisingly, spread of C. rodentium through the colon was delayed in TLR4
      deficient mice, whereas the duration of the infection was unaffected, indicating
      that TLR4-mediated responses against this A/E pathogen are not host protective
      and are ultimately maladaptive to the host, contributing to both the morbidity
      and the pathology seen during infection.

PMID- 16622188
TI  - The Helicobacter pylori cag pathogenicity island protein CagN is a bacterial
      membrane-associated protein that is processed at its C terminus.
AB  - Helicobacter pylori infects nearly half the world's population and is associated
      with a spectrum of gastric maladies. Infections with cytotoxin-associated gene
      pathogenicity island (cag PAI)-containing strains are associated with an
      increased risk for gastric cancer. The cag PAI contains genes encoding a type IV
      secretion system (T4SS) and a delivered effector, CagA, that becomes tyrosine
      phosphorylated upon delivery into host cells and initiates changes in cell
      signaling. Although some cag PAI genes have been shown to be required for CagA
      delivery, a subset of which are homologues of T4SS genes from Agrobacterium
      tumefaciens, the majority have no known function or homologues. We have performed
      a detailed investigation of one such cag PAI protein, CagN, which is encoded by
      the gene HP0538. Our results show that CagN is not delivered into host cells and
      instead is associated with the bacterial membrane. We demonstrate that CagN is
      cleaved at its C terminus by a mechanism that is independent of other cag PAI
      proteins. Finally, we show that a delta cagN mutant is not impaired in its
      ability to deliver CagA to gastric epithelial cells and initiate cell elongation.

PMID- 16622189
TI  - The hemoglobin receptor protein of porphyromonas gingivalis inhibits receptor
      activator NF-kappaB ligand-induced osteoclastogenesis from bone marrow
      macrophages.
AB  - Extracellular proteinaceous factors of Porphyromonas gingivalis, a periodontal
      pathogen, that influence receptor activator of nuclear factor-kappaB (NF-kappaB)
      ligand (RANKL)-induced osteoclastogenesis from bone marrow macrophages were
      investigated. The culture supernatant of P. gingivalis had the ability to inhibit
      RANKL-induced in vitro osteoclastogenesis. A major protein of the culture
      supernatant, hemoglobin receptor protein (HbR), suppressed RANKL-induced
      osteoclastogenesis in a dose-dependent fashion. HbR markedly inhibited RANKL
      induced osteoclastogenesis when present in the culture for the first 24 h after
      addition of RANKL, whereas no significant inhibition was observed when HbR was
      added after 24 h or later, implying that HbR might interfere with only the
      initial stage of RANKL-mediated differentiation. HbR tightly bound to bone marrow
      macrophages and had the ability to induce phosphorylation of ERK, p38, NF-kappaB,
      and Akt. RANKL-induced phosphorylation of ERK, p38, and NF-kappaB was not
      suppressed by HbR, but that of Akt was markedly suppressed. HbR inhibited RANKL
      mediated induction of c-Fos and NFATc1. HbR could induce beta interferon (IFN
      beta) from bone marrow macrophages, but the induction level of IFN-beta might not
      be sufficient to suppress RANKL-mediated osteoclastogenesis, implying presence of
      an IFN-beta-independent pathway in HbR-mediated inhibition of osteoclastogenesis.
      Since rapid and extensive destruction of the alveolar bone causes tooth loss,
      resulting in loss of the gingival crevice that is an anatomical niche for
      periodontal pathogens such as P. gingivalis, the suppressive effect of HbR on
      osteoclastogenesis may help the microorganism exist long in the niche.

PMID- 16622190
TI  - A C-terminal domain targets the Pseudomonas aeruginosa cytotoxin ExoU to the
      plasma membrane of host cells.
AB  - ExoU, a phospholipase injected into host cells by the type III secretion system
      of Pseudomonas aeruginosa, leads to rapid cytolytic cell death. Although the
      importance of ExoU in infection is well established, the mechanism by which this
      toxin kills host cells is less clear. To gain insight into how ExoU causes cell
      death, we examined its subcellular localization following transfection or type
      III secretion/translocation into HeLa cells. Although rapid cell lysis precluded
      visualization of wild-type ExoU by fluorescence microscopy, catalytically
      inactive toxin was readily detected at the periphery of HeLa cells. Biochemical
      analysis confirmed that ExoU was targeted to the membrane fraction of transfected
      cells. Visualization of ExoU peptides fused with green fluorescent protein
      indicated that the domain responsible for this targeting was in the C terminus of
      ExoU, between residues 550 and 687. Localization to the plasma membrane occurred
      within 1 h of expression, which is consistent with the kinetics of cytotoxicity.
      Together, these results indicate that a domain between residues 550 and 687 of
      ExoU targets this toxin to the plasma membrane, a process that may be important
      in cytotoxicity.

PMID- 16622191
TI  - Bacterial sinusitis and otitis media following influenza virus infection in
      ferrets.
AB  - Streptococcus pneumoniae is the leading cause of otitis media, sinusitis, and
      pneumonia. Many of these infections result from antecedent influenza virus
      infections. In this study we sought to determine whether the frequency and
      character of secondary pneumococcal infections differed depending on the strain
      of influenza virus that preceded bacterial challenge. In young ferrets infected
      with influenza virus and then challenged with pneumococcus, influenza viruses of
      any subtype increased bacterial colonization of the nasopharynx. Nine out of 10
      ferrets infected with H3N2 subtype influenza A viruses developed either sinusitis
      or otitis media, while only 1 out of 11 ferrets infected with either an H1N1
      influenza A virus or an influenza B virus did so. These data may partially
      explain why bacterial complication rates are higher during seasons when H3N2
      viruses predominate. This animal model will be useful for further study of the
      mechanisms that underlie viral-bacterial synergism.

PMID- 16622192
TI  - Staphylococcus aureus escapes more efficiently from the phagosome of a cystic
      fibrosis bronchial epithelial cell line than from its normal counterpart.
AB  - Staphylococcus aureus is frequently the initial bacterium isolated from young
      cystic fibrosis (CF) patients, and yet its role in CF disease progression has not
      been determined. Recent data from our lab demonstrates that S. aureus can invade
      and replicate within the CF tracheal epithelial cell line (CFT-1). Here we
      describe the finding that the fate of internalized S. aureus in CFT-1 cells
      differs from its complemented counterpart (LCFSN). S. aureus strain RN6390 was
      able to replicate within the mutant CFT-1 cells after invasion but not in the
      complemented LCFSN cells. At 1 h postinvasion, S. aureus containing vesicles
      within both cell lines acquired vacuolar-ATPase, lysosomal markers LAMP 1 and 2,
      and the lysomotrophic dye LysoTracker to a similar degree. However, at 4 h
      postinvasion, the percentage of S. aureus within CFT-1 cells associated with
      these markers decreased significantly compared to LCFSN, where the association
      approached 100%. Transmission electron microscopic analysis revealed that the
      majority of bacteria within CFT-1 cells were free in the cytosol at 4 h after
      invasion, whereas most S. aureus bacteria internalized by LCFSN cells remained
      within vesicles. These results demonstrate a fundamental difference in the fate
      of live S. aureus after invasion of CFT-1 versus LCFSN cell lines and may explain
      the propensity of S. aureus to cause chronic lung infection in CF patients.

PMID- 16622193
TI  - The NKG2D-activating receptor mediates pulmonary clearance of Pseudomonas
      aeruginosa.
AB  - The NKG2D-activating receptor is expressed on cytotoxic lymphocytes and interacts
      with ligands expressed on the surface of cells stressed by pathogenic and
      nonpathogenic stimuli. In this study, we investigated the physiologic importance
      of NKG2D receptor-ligand interactions in response to acute pulmonary Pseudomonas
      aeruginosa infection. P. aeruginosa infection increased the expression of mouse
      NKG2D ligands (Rae1) in airway epithelial cells and alveolar macrophages in vivo
      and also increased the cell surface expression of human NKG2D ligands (ULBP2) on
      airway epithelial cells in vitro. NKG2D receptor blockade with a specific
      monoclonal antibody inhibited the pulmonary clearance of P. aeruginosa. NKG2D
      receptor blockade also resulted in decreased production of Th1 cytokines and
      nitric oxide in the lungs of P. aeruginosa-infected mice. Additionally, NKG2D
      receptor blockade reduced the epithelial cell sloughing that accompanies P.
      aeruginosa infection. Macrophage phagocytosis and bronchoalveolar lavage
      cellularity were not different in P. aeruginosa-infected mice with and without
      NKG2D receptor blockade. These results demonstrate the importance of NKG2D
      mediated immune activation in the clearance of acute bacterial infection and
      suggest that epithelial cell-lymphocyte interactions mediate pulmonary cytokine
      production, epithelial cell integrity, and bacterial clearance.

PMID- 16622194
TI  - OspE2 of Shigella sonnei is required for the maintenance of cell architecture of
      bacterium-infected cells.
AB  - The OspE2 product of Shigella spp., the expression of which is regulated by the
      mxiE gene, is secreted through a type III secretion system into host cells. We
      investigated the function of OspE2 of Shigella sonnei by using cultured
      epithelial cells. Cells invaded by an ospE2 deletion mutant altered their
      morphology into the rounding shape, which was not due to cell death, whereas
      cells invaded by the wild-type strain kept their cell shape intact. The ospE2
      mutation did not affect initial cell entry and multiplication in cells, but the
      mutant formed smaller-than-normal plaques on cell monolayers, indicating a
      deficiency in cell-to-cell spread by the bacteria. An mxiE deletion mutant also
      showed changes in cell morphology and deficiency in bacterial spread to adjacent
      cells. In cells invaded by the ospE2 mutant, disturbance of actin stress fibers
      was prominent at 3 h after invasion. Analysis of OspE2 localization indicated
      that the OspE2 protein accumulated on focal contact-like structures in the
      infected host cells. These results suggest that colocalization of the OspE2
      protein in the focal contacts of infected cells may function to maintain an
      intact cell morphology. The morphological change induced by invasion of the ospE2
      mutant may affect secondary bacterial transmission.

PMID- 16622195
TI  - Host genetics of Bordetella pertussis infection in mice: significance of Toll
      like receptor 4 in genetic susceptibility and pathobiology.
AB  - The susceptibility to and the severity of Bordetella pertussis infections in
      infants and children varies widely, suggesting that genetic differences between
      individuals influence the course of infection. We have previously identified
      three novel loci that influence the severity of whooping cough by using
      recombinant congenic strains of mice: Bordetella pertussis susceptibility loci 1,
      2, and 3 (Bps1, -2, and -3). Because these loci could not account for all genetic
      differences between mice, we extended our search for additional susceptibility
      loci. We therefore screened 11 inbred strains of mice for susceptibility to a
      pertussis infection after intranasal infection. Susceptibility was defined by the
      number of bacteria in the lungs, being indicative of the effect between the
      clearance and replication of bacteria. The most resistant (A/J) and the most
      susceptible (C3H/HeJ) strains were selected for further genetic and phenotypic
      characterization. The link between bacterial clearance and chromosomal location
      was investigated with 300 F2 mice, generated by crossing A/J and C3H/HeJ mice. We
      found a link between the delayed clearance of bacteria from the lung and a large
      part of chromosome 4 in F2 mice with a maximum log of the odds score of 33.6 at
      65.4 Mb, which is the location of Tlr4. C3H/HeJ mice carry a functional mutation
      in the intracellular domain of Tlr4. This locus accounted for all detectable
      genetic differences between these strains. Compared to A/J mice, C3H/HeJ mice
      showed a delayed clearance of bacteria from the lung, a higher relative lung
      weight, and increased body weight loss. Splenocytes from infected C3H/HeJ mice
      produced almost no interleukin-1beta (IL-1beta) and tumor necrosis factor alpha
      (TNF-alpha) upon ex vivo restimulation with B. pertussis compared to A/J mice and
      also showed a delayed gamma interferon (IFN-gamma) production. TNF-alpha
      expression in the lungs 3 days after infection was increased fivefold compared to
      uninfected controls in A/J mice and was not affected in C3H/HeJ mice. In
      conclusion, Tlr4 is a major host factor explaining the differences in the course
      of infection between these inbred strains of mice. Functional Tlr4 is essential
      for an efficient IL-1-beta, TNF-alpha, and IFN-gamma response; efficient
      clearance of bacteria from the lung; and reduced lung pathology.

PMID- 16622196
TI  - Effect of novel A2A adenosine receptor agonist ATL 313 on Clostridium difficile
      toxin A-induced murine ileal enteritis.
AB  - Clostridium difficile is a spore-forming, anaerobic, gram-positive bacillus that
      releases two main virulence factors: toxins A and B. Toxin A plays an important
      pathogenic role in antibiotic-induced diarrhea and pseudomembranous colitis, a
      condition characterized by intense mucosal inflammation and secretion. Agonist
      activity at A2A adenosine receptors attenuates inflammation and damage in many
      tissues. This study evaluated the effects of a new selective A2A adenosine
      receptor agonist (ATL 313) on toxin A-induced injury in murine ileal loops. ATL
      313 (0.5 to 5 nM) and/or the A2A adenosine receptor antagonist (ZM241385; 5 nM)
      or phosphate-buffered saline (PBS) were injected into ileal loops immediately
      prior to challenge with toxin A (1 to 10 microg/loop) or PBS. Intestinal fluid
      volume/length and weight/length ratios were calculated 3 h later. Ileal tissues
      were collected for the measurement of myeloperoxidase, adenosine deaminase
      activity, tumor necrosis factor alpha (TNF-alpha) production, histopathology, and
      detection of cell death by the TUNEL (terminal deoxynucleotidyltransferase
      mediated dUTP-biotin nick end labeling) method. Toxin A significantly increased
      volume/length and weight/length ratios in a dose-dependent fashion. ATL 313
      treatment significantly (P < 0.05) reduced toxin A-induced secretion and edema,
      prevented mucosal disruption, and neutrophil infiltration as measured by
      myeloperoxidase activity. ATL 313 also reduced the toxin A-induced TNF-alpha
      production and adenosine deaminase activity and prevented toxin A-induced cell
      death. These protective effects of ATL 313 were reversed by ZM241385. In
      conclusion, the A2A adenosine receptor agonist, ATL 313, reduces tissue injury
      and inflammation in mice with toxin A-induced enteritis. The finding of increased
      ileal adenosine deaminase activity following the administration of toxin A is new
      and might contribute to the pathogenesis of the toxin A-induced enteritis by
      deaminating endogenous adenosine.

PMID- 16622197
TI  - Leishmania donovani requires functional Cdc42 and Rac1 to prevent phagosomal
      maturation.
AB  - Leishmania donovani promastigotes survive inside macrophage phagosomes by
      inhibiting phagosomal maturation. The main surface glycoconjugate on
      promastigotes, lipophosphoglycan (LPG), is crucial for survival and mediates the
      formation of a protective shell of F-actin around the phagosome. Previous studies
      have demonstrated that this effect involves inhibition of protein kinase C alpha.
      The present study shows that functional Cdc42 and Rac1 are required for the
      formation of F-actin around L. donovani phagosomes. Moreover, we present data
      showing that phagosomes containing LPG-defective L. donovani, which is unable to
      induce F-actin accumulation, display both elevated levels of periphagosomal F
      actin and impaired phagosomal maturation in macrophages with permanently active
      forms of Cdc42 and Rac1. We conclude that L. donovani engages Cdc42 and Rac1 to
      build up a protective coat of F-actin around its phagosome to prevent phagosomal
      maturation.

PMID- 16622198
TI  - Maternal immunity provides protection against pertussis in newborn piglets.
AB  - Pertussis continues to be a significant cause of morbidity and mortality in
      infants and young children worldwide. Methods to control the disease are based on
      vaccination with either whole-cell or acellular vaccines or treatment with
      antibiotics. However, despite worldwide vaccination infants are still at the
      highest risk for the disease. Here we used our newly developed newborn-piglet
      model to investigate whether transfer of maternal immunity can protect newborn
      piglets against infection with Bordetella pertussis. Pregnant sows were
      vaccinated with heat-inactivated B. pertussis or treated with saline (controls).
      Newborn piglets were allowed to suckle colostrum and milk for 4 to 5 days before
      they were challenged with 5 x 10(9) CFU of bacteria intrapulmonarily. Elevated
      levels of B. pertussis-specific secretory immunoglobulin A (S-IgA) and IgG
      antibodies were found in the colostrum and serum of vaccinated sows but not in
      those of control sows. Subsequently, significant levels of specific IgG and S-IgA
      were detected in the serum and bronchoalveolar lavage fluid of piglets born to
      vaccinated sows. Following infection with 5 x 10(9) CFU of B. pertussis, clinical
      symptoms, pathological alterations, and bacterial shedding were significantly
      reduced in piglets that had received passively transferred immunity. Thus, our
      results demonstrate that maternal immunization might represent an alternative
      approach to provide protection against pertussis in young infants.

PMID- 16622199
TI  - The most polymorphic residue on Plasmodium falciparum apical membrane antigen 1
      determines binding of an invasion-inhibitory antibody.
AB  - Apical membrane antigen 1 (AMA1) is currently one of the leading malarial vaccine
      candidates. Anti-AMA1 antibodies can inhibit the invasion of erythrocytes by
      Plasmodium merozoites and prevent the multiplication of blood-stage parasites.
      Here we describe an anti-AMA1 monoclonal antibody (MAb 1F9) that inhibits the
      invasion of Plasmodium falciparum parasites in vitro. We show that both
      reactivity of MAb 1F9 with AMA1 and MAb 1F9-mediated invasion inhibition were
      strain specific. Site-directed mutagenesis of a fragment of AMA1 displayed on M13
      bacteriophage identified a single polymorphic residue in domain I of AMA1 that is
      critical for MAb 1F9 binding. The identities of all other polymorphic residues
      investigated in this domain had little effect on the binding of the antibody.
      Examination of the P. falciparum AMA1 crystal structure localized this residue to
      a surface-exposed alpha-helix at the apex of the polypeptide. This description of
      a polymorphic inhibitory epitope on AMA1 adds supporting evidence to the
      hypothesis that immune pressure is responsible for the polymorphisms seen in this
      molecule.

PMID- 16622200
TI  - Differential expression and transcriptional analysis of the alpha-2,3
      sialyltransferase gene in pathogenic Neisseria spp.
AB  - Alpha-2,3-sialyltransferase (Lst) is expressed on the outer membrane of Neisseria
      gonorrhoeae and Neisseria meningitidis and sialylates surface lipooligosaccharide
      (LOS), facilitating resistance to complement-mediated killing. The enzyme is
      constitutively expressed from a single gene (lst) and does not undergo antigenic
      or phase variation. We observed that Triton X-100 extracts of N. gonorrhoeae
      strain F62 contain about fivefold more sialyltransferase (Stase) activity than
      extracts of N. meningitidis strain MC58 [symbol: see text]3 a serogroup B
      acapsulate mutant. We confirmed and expanded upon this observation by showing
      that extracts of 16 random N. gonorrhoeae isolates contain various amounts of
      Stase activity, but, on average, 2.2-fold-more Stase activity than extracts of 16
      N. meningitidis clinical isolates, representing several serogroups and
      nongroupable strains. Northern and real-time reverse transcription-PCR analysis
      of lst transcript levels in N. gonorrhoeae and N. meningitidis revealed that N.
      gonorrhoeae strains express more lst transcript than N. meningitidis strains.
      Although transcript levels correlate with average Stase activity observed in the
      two species, there was not a direct correlation between lst transcript levels and
      Stase activity among individual isolates of each species. Comparison of lst
      upstream (5'lst) regions of N. gonorrhoeae and N. meningitidis revealed striking
      sequence differences characteristic of the two pathogens. N. gonorrhoeae 5'lst
      regions possess 30-bp and 13-bp elements present as single elements or as tandem
      repeats that exist only as single elements in the 5'lst regions of N.
      meningitidis isolates. In addition, the 5'lst regions of N. meningitidis strains
      have 105-bp transposon-like Correia elements which are absent in N. gonorrhoeae.
      Chromosomal N. gonorrhoeae 5'lst::lacZ translational fusions expressed 4.75 +/-
      0.09-fold (n = 4) higher beta-galactosidase (beta-gal) activity than N.
      meningitidis 5'lst::lacZ fusions in a host-independent manner, indicating
      differential expression is governed at least in part by sequence variations in
      the 5'lst regions. Reporter fusion assays and promoter-mapping analysis revealed
      that N. gonorrhoeae and N. meningitidis use different promoters with different
      strengths to transcribe lst. In N. gonorrhoeae, a strong sigma 70 promoter 80 bp
      upstream of the translational start site is used to transcribe lst, whereas this
      promoter is inactive in N. meningitidis. In N. meningitidis, a weak sigma 70
      promoter at the 3' terminus of a 105-bp Correia repeat-enclosed element 99 bp
      upstream of the translational start site is used to transcribe lst. We conclude
      that differential Stase expression between N. gonorrhoeae and N. meningitidis is
      due at least in part to differential lst gene transcription.

PMID- 16622201
TI  - Expression of Haemophilus ducreyi collagen binding outer membrane protein NcaA is
      required for virulence in swine and human challenge models of chancroid.
AB  - Haemophilus ducreyi, the etiologic agent of the sexually transmitted genital
      ulcer disease chancroid, has been shown to associate with dermal collagen fibers
      within infected skin lesions. Here we describe NcaA, a previously uncharacterized
      outer membrane protein that is important for H. ducreyi collagen binding and host
      colonization. An H. ducreyi strain lacking the ncaA gene was impaired in
      adherence to type I collagen but not fibronectin (plasma or cellular form) or
      heparin. The mutation had no effect on serum resistance or binding to HaCaT
      keratinocytes or human foreskin fibroblasts in vitro. Escherichia coli expressing
      H. ducreyi NcaA bound to type I collagen, demonstrating that NcaA is sufficient
      to confer collagen attachment. The importance of NcaA in H. ducreyi pathogenesis
      was assessed using both swine and human experimental models of chancroid. In the
      swine model, 20% of lesions from sites inoculated with the ncaA mutant were
      culture positive for H. ducreyi 7 days after inoculation, compared to 73% of wild
      type-inoculated sites. The average number of CFU recovered from mutant-inoculated
      lesions was also significantly reduced compared to that recovered from wild-type
      inoculated sites at both 2 and 7 days after inoculation. In the human challenge
      model, 8 of 30 sites inoculated with wild-type H. ducreyi progressed to the
      pustular stage, compared to 0 of 30 sites inoculated with the ncaA mutant.
      Together these results demonstrate that the collagen binding protein NcaA is
      required for H. ducreyi infection.

PMID- 16622202
TI  - LfhA, a novel factor H-binding protein of Leptospira interrogans.
AB  - The early phase of leptospiral infection is characterized by the presence of live
      organisms in the blood. Pathogenic Leptospira interrogans is resistant to the
      alternative pathway of complement mediated-killing, while nonpathogenic members
      of the genus are not. Consistent with that observation, only pathogenic
      leptospires bound factor H, a host fluid-phase regulator of the alternative
      complement pathway. Ligand affinity blot analyses revealed that pathogenic L.
      interrogans produces at least two factor H-binding proteins. Through screening of
      a lambda phage expression library, we identified one of these as the novel
      membrane protein LfhA. Ligand affinity assays and surface plasmon resonance
      analyses of recombinant LfhA revealed specific binding of both factor H and
      factor H-related protein 1. Serological examination of infected humans and horses
      demonstrated that LfhA is expressed by L. interrogans during mammalian infection.
      LfhA may therefore contribute to the resistance of pathogenic leptospires to
      complement-mediated killing during leptospiremic phases of the disease.

PMID- 16622203
TI  - Brucella abortus rough mutants induce macrophage oncosis that requires bacterial
      protein synthesis and direct interaction with the macrophage.
AB  - Previous studies suggest that smooth Brucella organisms inhibit macrophage
      apoptosis. In contrast, necrotic cell death of macrophages infected with rough
      Brucella organisms in vitro has been reported, which may in part explain the
      failure of some rough organisms to thrive. To characterize these potential
      macrophage killing mechanisms, J774.A1 murine macrophages were infected with
      Brucella abortus S2308-derived rough mutant CA180. Electron microscopic analysis
      and polyethylene glycol protection assays revealed that the cells were killed as
      a result of necrosis and oncosis. This killing was shown to be unaffected by
      treatment with carbenicillin, an inhibitor of bacterial cell wall biosynthesis
      and, indirectly, replication. In contrast, chloramphenicol treatment of
      macrophages infected at multiplicities of infection exceeding 10,000 prevented
      cell death, despite internalization of large numbers of bacteria. Similarly, heat
      killed and gentamicin-killed CA180 did not induce cytopathic effects in the
      macrophage. These results suggested that killing of infected host cells requires
      active bacterial protein synthesis. Cytochalasin D treatment revealed that
      internalization of the bacteria was necessary to initiate killing. Transwell
      experiments demonstrated that cell death is not mediated by a diffusible product,
      including tumor necrosis factor alpha and nitric oxide, but does require direct
      contact between host and pathogen. Furthermore, macrophages preinfected with B.
      abortus S2308 or pretreated with B. abortus O polysaccharide did not prevent
      rough CA180-induced cell death. In conclusion, Brucella rough mutant infection
      induces necrotic and oncotic macrophage cell death that requires bacterial
      protein synthesis and direct interaction of bacteria with the target cells.

PMID- 16622204
TI  - Outer membrane protein A of Escherichia coli O157:H7 stimulates dendritic cell
      activation.
AB  - Outer membrane protein A (OmpA) is located in the membrane of Escherichia coli
      and other gram-negative bacteria and plays a multifunctional role in bacterial
      physiology and pathogenesis. In enterohemorrhagic E. coli (EHEC), especially
      serotype O157:H7, OmpA interacts with cultured human intestinal cells and likely
      acts as an important component to stimulate the immune response during infection.
      To test this hypothesis, we analyzed the effect of EHEC OmpA on cytokine
      production by dendritic cells (DCs) and on DC migration across polarized
      intestinal epithelial cells. OmpA induced murine DCs to secrete interleukin-1 (IL
      1), IL-10, and IL-12 in a dose-dependent manner, and this effect was independent
      of Toll-like receptor 4. Although DCs displayed differential responses to EHEC
      OmpA and OmpA-specific antibodies enhanced DC cytokine secretion, we cannot
      discard that other EHEC surface elements were likely to be involved. While OmpA
      was required for bacterial binding to polarized Caco-2 cells, it was not needed
      for the induction of cytokine production by Caco-2 cells or for human DC
      migration across polarized cells.

PMID- 16622205
TI  - The mycobacterial 38-kilodalton glycolipoprotein antigen activates the mitogen
      activated protein kinase pathway and release of proinflammatory cytokines through
      Toll-like receptors 2 and 4 in human monocytes.
AB  - Although the 38-kDa glycolipoprotein of Mycobacterium tuberculosis H37Rv is known
      to evoke prominent cellular and humoral immune responses in human tuberculosis
      (TB), little information is known about intracellular regulatory mechanisms
      involved in 38-kDa antigen (Ag)-induced host responses. In this study, we found
      that purified 38-kDa glycolipoprotein activates mitogen-activated protein kinases
      (MAPKs; extracellular signal-regulated kinase 1/2 [ERK1/2] and p38) and induces
      tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in human
      monocytes. When the 38-kDa Ag was applied to monocytes from TB patients and
      healthy controls, the activation of ERK1/2 and p38 MAPK and the subsequent
      cytokine secretion were greater in the monocytes from the active pulmonary TB
      patients than in monocytes from the healthy controls. Additionally, neutralizing
      antibodies for Toll-like receptor 2 (TLR2) or TLR4 significantly reduced the
      ERK1/2 and p38 activation induced by the 38-kDa protein when the antibodies were
      applied to HEK293 cells overexpressing TLR2 or TLR4 as well as human primary
      monocytes. Furthermore, the inhibition of TLR2 significantly, and that of TLR4
      partially, decreased the 38-kDa Ag-induced secretion of TNF-alpha and IL-6 in
      human monocytes. The intact protein moieties of the 38-kDa protein were
      responsible for biologic activities by this Ag. These data collectively
      demonstrate that the 38-kDa glycolipoprotein, acting through both TLR2 and TLR4,
      induces the activation of the ERK1/2 and p38 MAPK pathways, which in turn play an
      essential role in TNF-alpha and IL-6 expression during mycobacterial infection.

PMID- 16622206
TI  - Campylobacter jejuni induces maturation and cytokine production in human
      dendritic cells.
AB  - Campylobacter jejuni is a leading bacterial cause of human diarrheal disease in
      both developed and developing nations. Colonic mucosal invasion and the resulting
      host inflammatory responses are thought to be the key contributing factors to the
      dysenteric form of this disease. Dendritic cells (DCs) play an important role in
      both the innate and adaptive immune responses to microbial infection. In this
      study, the interaction between human monocyte-derived dendritic cells and C.
      jejuni was studied. We found that C. jejuni was readily internalized by DCs over
      a 2-h period. However, after a prolonged infection period (24 or 48 h) with C.
      jejuni, only a few viable bacteria remained intracellularly. Minimal cytotoxicity
      of C. jejuni to dendritic cells was observed. C. jejuni induced the maturation of
      dendritic cells over 24 h, as indicated by up-regulation of cell surface marker
      proteins CD40, CD80, and CD86. In addition, Campylobacter-infected DCs triggered
      activation of NF-kappaB and significantly stimulated production of interleukin
      1beta (IL-1beta), IL-6, IL-8, IL-10, IL-12, gamma interferon, and tumor necrosis
      factor alpha (TNF-alpha) compared to uninfected DCs. Active bacterial invasion of
      DCs was not necessary for the induction of these cytokines, as heat-killed C.
      jejuni stimulated similar levels of cytokine production as live bacteria.
      Purified lipooligosaccharide of C. jejuni appears to be the major stimulant for
      the increased production of cytokines by DCs. Taken together, these data indicate
      that during infection, Campylobacter triggers an innate inflammatory response
      through increased production of IL-1beta, IL-6, IL-8, and TNF-alpha and initiates
      a Th1-polarized adaptive immune response as predicted from the high level of
      production of IL-12.

PMID- 16622207
TI  - Safety, immunogenicity, and efficacy of prime-boost immunization with recombinant
      poxvirus FP9 and modified vaccinia virus Ankara encoding the full-length
      Plasmodium falciparum circumsporozoite protein.
AB  - Heterologous prime-boost immunization with DNA and various recombinant poxviruses
      encoding malaria antigens is capable of inducing strong cell-mediated immune
      responses and partial protection in human sporozoite challenges. Here we report a
      series of trials assessing recombinant fowlpox virus and modified vaccinia virus
      Ankara encoding the Plasmodium falciparum circumsporozoite protein in various
      prime-boost combinations, doses, and application routes. For the first time,
      these vaccines were administered intramuscularly and at doses of up to 5 x 10(8)
      PFU. Vaccines containing this antigen proved safe and induced modest immune
      responses but showed no evidence of efficacy in a sporozoite challenge.

PMID- 16622208
TI  - Splenic gammadelta T cells regulated by CD4+ T cells are required to control
      chronic Plasmodium chabaudi malaria in the B-cell-deficient mouse.
AB  - Little is known about the function and regulation of splenic gammadelta T cells
      during chronic Plasmodium chabaudi malaria. The splenic gammadelta T-cell
      population continues to expand, reaching levels equal to 4 times the number of
      splenocytes in an uninfected mouse. Splenic gammadelta T cells from J(H)-/- mice
      with chronic malaria expressed Vgamma1+ or Vdelta4+ in the same ratio as
      uninfected controls with Vgamma1 cells dominating, but the Vgamma2 ratio declined
      about twofold. Gammadelta T cells from G8 mice specific for the TL antigen
      increased only 2-fold in number, compared with 10-fold in BALB/c controls, but G8
      gammadelta T cells failed to express the B220 activation marker. Elimination of
      the parasite by drug treatment caused a slow depletion in the number of splenic
      gammadelta, CD4+, and CD8+ T cells. Following challenge, drug-cured J(H)-/- mice
      exhibited nearly identical parasitemia time courses as naive controls. Depletion
      of either CD4+ T cells or gammadelta T cells from chronically infected J(H)-/-
      mice by monoclonal antibody treatment resulted in an immediate and significant (P
      < 0.05) exacerbation of parasitemia coupled with a marked decrease in splenic
      gammadelta T-cell numbers. The number of CD4+ T cells, in contrast, did not
      decrease in mice after anti-T-cell receptor gammadelta treatment. The results
      indicate that cell-mediated immunity against blood-stage malarial parasites
      during chronic malaria (i) requires the continued presence of blood-stage
      parasites to remain functional, (ii) is dependent upon both gammadelta T cells
      and CD4+ T cells, and (iii) lacks immunological memory.

PMID- 16622209
TI  - A reduced risk of infection with Plasmodium vivax and clinical protection against
      malaria are associated with antibodies against the N terminus but not the C
      terminus of merozoite surface protein 1.
AB  - Progress towards the development of a malaria vaccine against Plasmodium vivax,
      the most widely distributed human malaria parasite, will require a better
      understanding of the immune responses that confer clinical protection to patients
      in regions where malaria is endemic. The occurrence of clinical protection in P.
      vivax malaria in Brazil was first reported among residents of the riverine
      community of Portuchuelo, in Rondonia, western Amazon. We thus analyzed immune
      sera from this same human population to determine if naturally acquired humoral
      immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1,
      could be associated with reduced risk of infection and/or clinical protection.
      Our results demonstrated that this association could be established with anti
      PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed
      against the N terminus but not against the C terminus, in spite of the latter
      being more immunogenic and capable of natural boosting. This is the first report
      of a prospective study of P. vivax malaria demonstrating an association of
      reduced risk of infection and clinical protection with antibodies against an
      antigen of this parasite.

PMID- 16622211
TI  - Characterization of the opsonic and protective activity against Staphylococcus
      aureus of fully human monoclonal antibodies specific for the bacterial surface
      polysaccharide poly-N-acetylglucosamine.
AB  - Carbohydrate antigens are important targets of the immune system in clearing
      bacterial pathogens. Although the immune system almost exclusively uses
      antibodies in response to foreign carbohydrates, there is still much to learn
      about the role of different epitopes on the carbohydrate as targets of protective
      immunity. We examined the role of acetyl group-dependent and -independent
      epitopes on the staphylococcal surface of polysaccharide poly-N-acetylated
      glucosamine (PNAG) by use of human monoclonal antibodies (MAbs) specific for such
      epitopes. We utilized hybridoma technology to produce fully human immunoglobulin
      G2 (IgG2) MAbs from B cells of an individual post-Staphylococcus aureus infection
      and cloned the antibody variable regions to produce an IgG1 form of each original
      MAb. Specificity and functionality of the purified MAbs were tested in vitro
      using enzyme-linked immunosorbent assays, complement deposition, and
      opsonophagocytic assays. We found that a MAb (MAb F598) that bound the best to
      nonacetylated or backbone epitopes on PNAG had superior complement deposition and
      opsonophagocytic activity compared to two MAbs that bound optimally to PNAG that
      was expressed with a native level (>90%) of N-acetyl groups (MAbs F628 and F630).
      Protection of mice against lethality due to S. aureus strains Mn8 and Reynolds
      further showed that the backbone-specific MAb had optimal protective efficacy
      compared with the acetate-specific MAbs. These results provide evidence for the
      importance of epitope specificity in inducing the optimal protective antibody
      response to PNAG and indicate that MAbs to the deacetylated form of PNAG could be
      immunotherapeutic agents for preventing or treating staphylococcal infections.

PMID- 16622210
TI  - Protective immunity elicited by a divalent DNA vaccine encoding both the L7/L12
      and Omp16 genes of Brucella abortus in BALB/c mice.
AB  - This study was designed to evaluate the immunogenicity and the protective
      efficacy of a divalent fusion DNA vaccine encoding both the Brucella abortus
      L7/L12 protein (ribosomal protein) and Omp16 protein (outer membrane
      lipoprotein), designated pcDNA3.1-L7/L12-Omp16. Intramuscular injection of this
      divalent DNA vaccine into BALB/c mice elicited markedly both humoral and cellular
      immune responses. The specific antibodies exhibited a dominance of immunoglobulin
      G2a (IgG2a) over IgG1. In addition, the dual-gene DNA vaccine elicited a strong T
      cell proliferative response and induced a large amount of gamma interferon
      producing T cells upon restimulation in vitro with recombinant fusion protein
      L7/L12-Omp16, suggesting the induction of a typical T-helper-1-dominated immune
      response in vivo. This divalent DNA vaccine could also induce a significant level
      of protection against challenge with the virulent strain B. abortus 544 in BALB/c
      mice. Furthermore, the protection level induced by the divalent DNA vaccine was
      significantly higher than that induced by the univalent DNA vaccines pcDNA3.1
      L7/L12 or pcDNA3.1-Omp16. Taken together, the results of this study verify for
      the first time that the Omp16 gene can be a candidate target for a DNA vaccine
      against brucellosis. Additionally, a divalent genetic vaccine based on the L7/L12
      and Omp16 genes can elicit a stronger cellular immune response and better
      immunoprotection than the relevant univalent vaccines can.

PMID- 16622212
TI  - Partial reconstitution of the CD4+-T-cell compartment in CD4 gene knockout mice
      restores responses to tuberculosis DNA vaccines.
AB  - Reactivation tuberculosis (TB) is a serious problem in immunocompromised
      individuals, especially those with human immunodeficiency virus (HIV)
      coinfection. The adaptive immune response mediated by CD4+ and CD8+ T cells is
      known to confer protection against TB. Hence, vaccines against TB are designed to
      activate these two components of the immune system. Anti-TB DNA vaccines encoding
      the immunodominant proteins Ag85A, Ag85B, and PstS-3 from Mycobacterium
      tuberculosis are ineffective in mice lacking CD4+ T cells (CD4-/- mice). In this
      study, we demonstrate that reconstitution of the T-cell compartment in CD4-/-
      mice restores vaccine-specific antibody and gamma interferon (IFN-gamma)
      responses to these DNA vaccines. The magnitude of the immune responses correlated
      with the extent of reconstitution of the CD4+-T-cell compartment. Reconstituted
      mice vaccinated with DNA encoding PstS-3, known to encode a dominant D(b)
      restricted CD8+-T-cell epitope, displayed CD8+-T-cell responses not observed in
      CD4-/- mice. M. tuberculosis challenge in reconstituted mice led to the
      extravasation of IFN-gamma-producing CD4+ and CD8+ T cells into lungs, the
      primary site of bacterial replication. Importantly, a reconstitution of 12 to 15%
      of the CD4+-T-cell compartment resulted in Ag85B plasmid DNA-mediated protection
      against a challenge M. tuberculosis infection. Our findings provide evidence that
      anti-TB DNA vaccines could be effective in immunodeficient individuals after CD4+
      T-lymphocyte reconstitution, as may occur following antiretroviral therapy in
      HIV+ patients.

PMID- 16622213
TI  - In vivo activation of naive CD4+ T cells in nasal mucosa-associated lymphoid
      tissue following intranasal immunization with recombinant Streptococcus gordonii.
AB  - The antigen-specific primary activation of CD4+ T cells was studied in vivo by
      adoptive transfer of ovalbumin-specific transgenic T cells (KJ1-26+ CD4+)
      following intranasal immunization with recombinant Streptococcus gordonii. A
      strain of S. gordonii expressing on its surface a model vaccine antigen fused to
      the ovalbumin (OVA) peptide from position 323 to 339 was constructed and used to
      study the OVA-specific T-cell activation in nasal mucosa-associated lymphoid
      tissue (NALT), lymph nodes, and spleens of mice immunized by the intranasal
      route. The recombinant strain, but not the wild type, activated the OVA-specific
      CD4+ T-cell population in the NALT (89% of KJ1-26+ CD4+ T cells) just 3 days
      following immunization. In the cervical lymph nodes and in the spleen, the
      percentage of proliferating cells was initially low, but it reached the peak of
      activation at day 5 (90%). This antigen-specific clonal expansion of KJ1-26+ CD4+
      T cells after intranasal immunization was obtained with live and inactivated
      recombinant bacteria, and it indicates that the NALT is the site of antigen
      specific T-cell priming.

PMID- 16622214
TI  - RpoH mediates the expression of some, but not all, genes induced in Neisseria
      gonorrhoeae adherent to epithelial cells.
AB  - Neisseria gonorrhoeae (gonococcus [GC]), is highly adapted to the human host, the
      only known reservoir for gonococcal infection. However, since it is sexually
      transmitted, infection of a new host likely requires a regulatory response on the
      part of the gonococcus to respond to this significant change in environment. We
      previously showed that adherence of gonococci to epithelial cells results in
      changes of gene expression in the bacteria that presumably prepare them for
      subsequent steps in the infection process. Expression of the heat shock sigma
      factor gene, rpoH, was shown to be important for the invasion step, as gonococci
      depleted for rpoH were reduced in their ability to invade epithelial cells. Here,
      we show that of the genes induced in adherent gonococci, two are part of the
      gonococcal RpoH regulon. When RpoH is depleted, expression of these genes is no
      longer induced by host cell contact, indicating that RpoH is mediating the host
      cell induction response of these genes. One RpoH-dependent gene, NGO0376, is
      shown to be important for invasion of epithelial cells, consistent with earlier
      observations that RpoH is necessary for this step of infection. Two genes,
      NGO1684 and NGO0340, while greatly induced by host cell contact, were found to be
      RpoH independent, indicating that more than one regulator is involved in the
      response to host cell contact. Furthermore, NGO0340, but not NGO1684, was shown
      to be important for both adherence and invasion of epithelial cells, suggesting a
      complex regulatory network in the response of gonococci to contact with host
      cells.

PMID- 16622215
TI  - Identification and characterization of a hemolysin gene cluster in Vibrio
      anguillarum.
AB  - Vibrio anguillarum is a causative agent of vibriosis in fish. Hemolytic activity
      has been suggested as a virulence factor by contributing to hemorrhagic
      septicemia and diarrhea. In order to identify and characterize the hemolysin
      genes and examine the role of hemolytic activity in virulence, a mini-Tn10Kan
      mutagenesis clone bank of V. anguillarum was screened. While no hemolysin
      negative strains were observed, several mutants with two- to threefold-increased
      hemolytic activity were found. The region containing the insertion mutation was
      cloned, sequenced, and found to contain the V. anguillarum hemolysin (vah1) and
      two other open reading frames, coding for a putative lactonizing lipase (llpA)
      and a putative phospholipase (plp). The mini-Tn10Kan was inserted into plp. Site
      directed mutagenesis of each gene revealed that mutations in vah1 and llpA did
      not affect hemolytic activity, but insertions into plp caused a two- to threefold
      increase in hemolysis. Double mutations in plp and either vah1 or llpA resulted
      in wild-type hemolytic activity. Complementation of plp restored hemolytic
      activity to wild-type levels. Spectrophotometric determination of hemolysin
      specific activity revealed that activity on a per cell basis peaked during the
      first 2 h of growth in LB20. Real-time quantitative reverse transcriptase PCR
      used to quantitate transcription of the hemolysin genes plp and vah1 in V.
      anguillarum wild-type strains M93Sm and NB10 revealed that transcription of plp
      and vah1 peaked at 2 h of growth in LB20. Additionally, expression of vah1
      measured in the plp mutant strain, JL01, during the first 2 h of growth was >8
      times higher than that in M93Sm. Mutations in plp and llpA did not affect
      virulence of V. anguillarum. The mutation in vah1 attenuated V. anguillarum
      virulence in fish. These data show that several genes are responsible for
      hemolytic activity in V. anguillarum. At least three genes (plp, llpA, and vah1)
      are responsible for one hemolytic activity. The data also suggest that plp acts
      as a negative regulator of vah1 and llpA.

PMID- 16622216
TI  - Influence of Slc11a1 on the outcome of Salmonella enterica serovar Enteritidis
      infection in mice is associated with Th polarization.
AB  - Genetic analyses identified Ses1 as a significant quantitative trait locus
      influencing the carrier state of 129S6 mice following a sublethal challenge with
      Salmonella enterica serovar Enteritidis. Previous studies have determined that
      Slc11a1 was an excellent candidate gene for Ses1. Kinetics of infection in 129S6
      mice and Slc11a1-deficient (129S6-Slc11a1(tm1Mcg)) mice demonstrated that the
      wild-type allele of Slc11a1 contributed to the S. enterica serovar Enteritidis
      carrier state as early as 7 days postinfection. Gene expression profiling
      demonstrated that 129S6 mice had a significant up-regulation of proinflammatory
      genes associated with macrophage activation at day 10 postinfection, followed by
      a gradual increase in immunoglobulin transcripts, whereas 129S6-Slc11a1(tm1Mcg)
      mice had higher levels of immunoglobulins earlier in the infection. Quantitative
      reverse transcription-PCR revealed an increase in Th1 cytokine (Ifng and Il12)
      and Th1-specific transcription factor Tbx21 expression during infection in both
      the 129S6 and 129S6-Slc11a1(tm1Mcg) strains. However, the expression of Gata3, a
      transcription factor involved in Th2 polarization, Cd28, and Il4 was markedly
      increased in Slc11a1-deficient mice during infection, suggesting a predominant
      Th2 phenotype in 129S6-Slc11a1(tm1Mcg) animals following S. enterica serovar
      Enteritidis infection. A strong immunoglobulin G2a response, reflecting Th1
      activity, was observed only in 129S6 mice. All together, these results are
      consistent with an impact of Slc11a1 on Th cell differentiation during chronic S.
      enterica serovar Enteritidis infection. The presence of a Th2 bias in Slc11a1
      deficient mice is associated with improved bacterial clearance.

PMID- 16622217
TI  - Protection by meningococcal outer membrane protein PorA-specific antibodies and a
      serogroup B capsular polysaccharide-specific antibody in complement-sufficient
      and C6-deficient infant rats.
AB  - The relative contributions of antibody-induced complement-mediated bacterial
      lysis and antibody/complement-mediated phagocytosis to host immunity against
      meningococcal infections are currently unclear. Further, the in vivo effector
      functions of antibodies may vary depending on their specificity and Fc heavy
      chain isotype. In this study, a mouse immunoglobulin G2a (mIgG2a) monoclonal
      antibody (MN12H2) to meningococcal outer membrane protein PorA (P1.16), its human
      IgG subclass derivatives (hIgG1 to hIgG4), and an mIgG2a monoclonal antibody
      (Nmb735) to serogroup B capsular polysaccharide (B-PS) were evaluated for passive
      protection against meningococcal serogroup B strain 44/76-SL (B:15:P1.7,16) in an
      infant rat infection model. Complement component C6-deficient (PVG/c-) rats were
      used to assess the importance of complement-mediated bacterial lysis for
      protection. The PorA-specific parental mIgG2a and the hIgG1 to hIgG3 derivatives
      all induced efficient bactericidal activity in vitro in the presence of human or
      infant rat complement and augmented bacterial clearance in complement-sufficient
      HsdBrlHan:WIST rats, while the hIgG4 was unable to do so. In C6-deficient PVG/c-
      rats, lacking complement-mediated bacterial lysis, the augmentation of bacterial
      clearance by PorA-specific mIgG2a and hIgG1 antibodies was impaired compared to
      that in the syngeneic complement-sufficient PVG/c+ rat strain. This was in
      contrast to the case for B-PS-specific mIgG2a, which conferred similar protective
      activity in both rat strains. These data suggest that while anti-B-PS antibody
      can provide protection in the infant rats without membrane attack complex
      formation, the protection afforded by anti-PorA antibody is more dependent on the
      activation of the whole complement pathway and subsequent bacterial lysis.

PMID- 16622219
TI  - The 6-kilodalton early secreted antigenic target-responsive, asymptomatic
      contacts of tuberculosis patients express elevated levels of interleukin-4 and
      reduced levels of gamma interferon.
AB  - It is well known that the majority of healthy individuals exposed to
      Mycobacterium tuberculosis do not become clinically ill. We have previously shown
      that in recently exposed healthy contacts of tuberculosis (TB) patients, a strong
      immune response to the M. tuberculosis 6-kDa early secreted antigenic target
      (ESAT-6) virulence factor correlated with a higher risk of subsequent disease,
      although the mechanism was unclear at that time. Inspired by recent reports that
      elevated expression of interleukin-4 (IL-4) in health care workers exposed to M.
      tuberculosis also correlated with a higher risk of their subsequently developing
      disease, we examined expression of IL-4, its competitive antagonist IL-4delta2,
      and gamma interferon (IFN-gamma) in healthy household contacts of TB patients
      from Ethiopia. We then compared cytokine expression to their recognition of ESAT
      6 (which is largely restricted to members of the tuberculosis complex and which
      serves as a reliable marker of infection) or to Ag85A (an antigen that is
      conserved among the mycobacteria and serves as a nonspecific control). Our study
      shows that in these recently exposed individuals, there is a correlation between
      a strong response to ESAT-6 and elevated expression of IL-4. Further, elevated
      expression of IL-4 is associated with lower expression of its antagonistic splice
      variant IL-4delta2 and with the Th1 cytokine IFN-gamma, suggesting that in these
      at-risk individuals, immunity is skewed away from a protective Th1 response, even
      before the development of clinical symptoms.

PMID- 16622218
TI  - Toll-like receptor 2 is required for inflammatory responses to Francisella
      tularensis LVS.
AB  - Francisella tularensis, a gram-negative bacterium, is the etiologic agent of
      tularemia and has recently been classified as a category A bioterrorism agent.
      Infections with F. tularensis result in an inflammatory response that plays an
      important role in the pathogenesis of the disease; however, the cellular
      mechanisms mediating this response have not been completely elucidated. In the
      present study, we determined the role of Toll-like receptors (TLRs) in mediating
      inflammatory responses to F. tularensis LVS, and the role of NF-kappaB in
      regulating these responses. Stimulation of bone marrow-derived dendritic cells
      from C57BL/6 wild-type (wt) and TLR4-/- but not TLR2-/- mice, with live F.
      tularensis LVS elicited a dose-dependent increase in the production of tumor
      necrosis factor alpha. F. tularensis LVS also induced in a dose-dependent manner
      an up-regulation in the expression of the costimulatory molecules CD80 and CD86
      and of CD40 and the major histocompatibility complex class II molecules on
      dendritic cells from wt and TLR4-/- but not TLR2-/- mice. TLR6, not TLR1, was
      shown to be involved in mediating the inflammatory response to F. tularensis LVS,
      indicating that the functional heterodimer is TLR2/TLR6. Stimulation of dendritic
      cells with F. tularensis resulted in the activation of NF-kappaB, which resulted
      in a differential effect on the production of pro- and anti-inflammatory
      cytokines. Taken together, our results demonstrate the role of TLR2/TLR6 in the
      host's inflammatory response to F. tularensis LVS in vitro and the regulatory
      function of NF-kappaB in modulating the inflammatory response.

PMID- 16622220
TI  - Modulation of the triggering receptor expressed on the myeloid cell type 1
      pathway in murine septic shock.
AB  - The triggering receptor expressed on myeloid cell type 1 (TREM-1) is a cell
      surface molecule that has been identified on both human and murine
      polymorphonuclear neutrophils and mature monocytes. The activation of TREM-1 in
      the presence of microbial components amplifies the inflammatory response and may
      be responsible for the hyperresponsiveness observed during the initial stage of
      sepsis. To investigate the effect of the modulation of the TREM-1 pathway during
      experimental murine sepsis, we used analogue synthetic peptides derived from the
      extracellular moiety of TREM-1. The TREM-1 ligand was expressed on both
      peritoneal and peripheral neutrophils during experimental peritonitis in mice.
      The TREM-1 peptides inhibited the recognition by TREM-1 of its ligand and
      protected endotoxinic mice from death. In septic rats, the TREM-1 peptides
      improved the hemodynamic status, attenuated the development of lactic acidosis,
      modulated the production of such proinflammatory cytokines as tumor necrosis
      factor alpha and interleukin-1beta, and improved survival. The protective effect
      of these peptides on arterial pressure could partly be explained by a decreased
      production of nitric oxide. These data suggest that in vivo modulation of TREM-1
      might be a suitable therapeutic tool for the treatment of sepsis.

PMID- 16622221
TI  - Bordetella pertussis inhibition of interleukin-12 (IL-12) p70 in human monocyte
      derived dendritic cells blocks IL-12 p35 through adenylate cyclase toxin
      dependent cyclic AMP induction.
AB  - Bordetella pertussis, the causative agent of whooping cough, possesses an array
      of virulence factors, including adenylate cyclase toxin (ACT), relevant in the
      establishment of infection. Here we better define the impact of cyclic AMP (cAMP)
      intoxication due to the action of ACT on dendritic cell (DC)-driven immune
      response, by infecting monocyte-derived DC (MDDC) with an ACT-deficient B.
      pertussis mutant (ACT- 18HS19) or its parental strain (WT18323). Both strains
      induced MDDC maturation and antigen-presenting cell functions; however, only ACT-
      18HS19 infected MDDC-induced production of interleukin-12 (IL-12) p70. Gene
      expression analysis of the IL-12 cytokine family subunits revealed that both
      strains induced high levels of p40 (protein chain communal to IL-12 p70 and IL
      23) as well as p19, a subunit of IL-23. Conversely only ACT- 18HS19 infection
      induced consistent transcription of IL-12 p35, a subunit of IL-12 p70. Addition
      of the cAMP analogous D-butyril-cAMP (D-cAMP) abolished IL-12 p70 production and
      IL-12 p35 expression in ACT- 18HS19-infected MDDC. ACT- 18HS19 infection induced
      the expression of the transcription factors interferon regulatory factor 1 (IRF
      1) and IRF-8 and of beta interferon, involved in IL-12 p35 regulation, and the
      expression of these genes was inhibited by D-cAMP addition and in WT18323
      infected MDDC. The concomitant expression of IL-12 p70 and IL-23 allowed ACT-
      18HS19 to trigger a more pronounced T helper 1 polarization compared to WT18323.
      The present study suggests that ACT-dependent cAMP induction leads to the
      inhibition of pathways ultimately leading to IL-12 p35 production, thus
      representing a mechanism for B. pertussis to escape the host immune response.

PMID- 16622222
TI  - Murine malaria infection induces fetal loss associated with accumulation of
      Plasmodium chabaudi AS-infected erythrocytes in the placenta.
AB  - Malarial infection in nonimmune women is a risk factor for pregnancy loss, but
      the role that maternal antimalarial immune responses play in fetal compromise is
      not clear. We conducted longitudinal and serial sacrifice studies to examine the
      pathogenesis of malaria during pregnancy using the Plasmodium chabaudi AS/C57BL/6
      mouse model. Peak parasitemia following inoculation with 1,000 parasite-infected
      murine erythrocytes and survival were similar in infected pregnant and
      nonpregnant mice, although development of parasitemia and anemia was slightly
      accelerated in pregnant mice. Importantly, pregnant mice failed to maintain
      viable pregnancies, most aborting before day 12 of gestation. At abortion,
      maternal placental blood parasitemia was statistically significantly higher than
      peripheral parasitemia. Infected mice had similar increases in spleen size and
      cellularity which were statistically significantly higher than in uninfected
      mice. In contrast, splenocyte proliferation in response to mitogenic stimulation
      around peak parasitemia was statistically significantly reduced in both groups of
      infected mice compared to uninfected, nonpregnant mice, suggesting that
      lymphoproliferation is not a good indicator of the antimalarial immune responses
      in pregnant or nonpregnant animals. This study suggests that while pregnant and
      nonpregnant C57BL/6 mice are equally capable of mounting an effective immune
      response to and surviving P. chabaudi AS infection, pregnant mice cannot produce
      viable pups. Fetal loss appears to be associated with placental accumulation of
      infected erythrocytes. Further study is required to determine to what extent
      maternal antimalarial immune responses, anemia, and placental accumulation of
      parasites contribute to compromised pregnancy in this model.

PMID- 16622223
TI  - The ability of Mycobacterium avium subsp. paratuberculosis to enter bovine
      epithelial cells is influenced by preexposure to a hyperosmolar environment and
      intracellular passage in bovine mammary epithelial cells.
AB  - Mycobacterium avium subsp. paratuberculosis is the cause of Johne's disease in
      cattle and other ruminants. M. avium subsp. paratuberculosis infection of the
      bovine host is not well understood; however, it is assumed that crossing the
      bovine intestinal mucosa is important in order for M. avium subsp.
      paratuberculosis to establish infection. To examine the ability of M. avium
      subsp. paratuberculosis to infect bovine epithelial cells in vitro, Madin-Darby
      bovine kidney (MDBK) epithelial cells were exposed to M. avium subsp.
      paratuberculosis. It was observed that bacteria can establish infection and
      replicate within MDBK cells. M. avium subsp. paratuberculosis also has been
      reported to infect mammary tissue and milk, and we showed that M. avium subsp.
      paratuberculosis infects bovine mammary epithelial cells (MAC-T cell line). Using
      polarized MAC-T cell monolayers, it was also determined that M. avium subsp.
      paratuberculosis crosses apical and basolateral surfaces with approximately the
      same degree of efficiency. Because M. avium subsp. paratuberculosis can be
      delivered to the naive host by milk, it was investigated whether incubation of M.
      avium subsp. paratuberculosis with milk has an effect on invasion of MDBK cells.
      M. avium subsp. paratuberculosis exposed to milk entered epithelial cells with
      greater efficiency than M. avium subsp. paratuberculosis exposed to broth medium
      or water (P < 0.01). Growth of M. avium subsp. paratuberculosis within MAC-T
      cells also resulted in augmented ability to subsequently infect bovine MDBK cells
      (P < 0.001). Microarray analysis of intracellular M. avium subsp.
      paratuberculosis RNA indicates the increased transcription of genes which might
      be associated with an invasive phenotype.

PMID- 16622224
TI  - Mucosal adjuvant properties of the Shigella invasin complex.
AB  - The Shigella invasin complex (Invaplex) is an effective mucosal vaccine capable
      of protecting against Shigella challenge in animal models. The major antigenic
      constituents of Invaplex are the Ipa proteins and lipopolysaccharide. The cell
      binding capacity of the Ipa proteins prompted the investigation into the
      adjuvanticity of Invaplex. Using ovalbumin (OVA) as a model antigen, intranasal
      immunization with OVA combined with Invaplex was found to enhance anti-OVA serum
      immunoglobulin G (IgG) and IgA responses and induce OVA-specific mucosal antibody
      responses at sites located both proximal and distal to the immunization site. The
      immune responses induced with OVA and Invaplex were comparable in both magnitude
      and duration to the immune responses induced after immunization with OVA and
      cholera toxin. The OVA-specific immune response was characterized by high levels
      of serum IgG1 and increased production of interleukin-4 (IL-4), IL-5, or IL-10
      from lymphoid cells of immunized animals, suggesting a Th2 response. In addition
      to enhancing the immunogenicity of OVA, Invaplex-specific immune responses were
      also induced, indicating the potential for the development of a combination
      vaccine consisting of Invaplex and other immunogens. Preexisting Invaplex
      specific immunity did not interfere with the capacity to enhance the
      immunogenicity of a second, unrelated vaccine antigen, suggesting that Invaplex
      could be used as a mucosal adjuvant in multiple vaccine regimens.

PMID- 16622225
TI  - Levels of plasma immunoglobulin G with specificity against the cysteine-rich
      interdomain regions of a semiconserved Plasmodium falciparum erythrocyte membrane
      protein 1, VAR4, predict protection against malarial anemia and febrile episodes.
AB  - Antibodies to variant surface antigen have been implicated as mediators of
      malaria immunity in studies measuring immunoglobulin G (IgG) binding to infected
      erythrocytes. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an
      important target for these antibodies, but no study has directly linked the
      presence of PfEMP1 antibodies in children to protection. We measured plasma IgG
      levels to the cysteine-rich interdomain region 1alpha (CIDR1alpha) of VAR4 (VAR4
      CIDR1alpha), a member of a semiconserved PfEMP1 subfamily, by enzyme-linked
      immunosorbent assay in 561 Tanzanian individuals, who were monitored clinically
      for 7 months. The participants resided in Mkokola (a high-transmission village
      where malaria is holoendemic) or Kwamasimba (a moderate-transmission village).
      For comparison, plasma IgG levels to two merozoite surface protein 1 (MSP1)
      constructs, MSP1-19 and MSP1 block 2, and a control CIDR1 domain were measured.
      VAR4-CIDR1alpha antibodies were acquired at an earlier age in Mkokola than in
      Kwamasimba, but after the age of 10 years the levels were comparable in the two
      villages. After controlling for age and other covariates, the risk of having
      anemia at enrollment was reduced in VAR4-CIDR1alpha responders for Mkokola
      (adjusted odds ratio [AOR], 0.49; 95% confidence interval [CI], 0.29 to 0.88; P =
      0.016) and Kwamasimba (AOR, 0.33; 95% CI, 0.16 to 0.68; P = 0.003) villages. The
      risk of developing malaria fever was reduced among individuals with a measurable
      VAR4-CIDR1alpha response from Mkokola village (AOR, 0.51; 95% CI, 0.29 to 0.89; P
      = 0.018) but not in Kwamasimba. Antibody levels to the MSP1 constructs and the
      control CIDR1alpha domain were not associated with morbidity protection. These
      data strengthen the concept of developing vaccines based on PfEMP1.

PMID- 16622226
TI  - Signal transduction mechanism involved in Clostridium perfringens alpha-toxin
      induced superoxide anion generation in rabbit neutrophils.
AB  - Clostridium perfringens alpha-toxin induces the generation of superoxide anion
      (O2(-)) via production of 1,2-diacylglycerol (DG) in rabbit neutrophils. The
      mechanism of the generation, however, remains poorly understood. Here we report a
      novel mechanism for the toxin-induced production of O2(-) in rabbit neutrophils.
      Treatment of the cells with the toxin resulted in tyrosine phosphorylation of a
      protein of about 140 kDa. The protein reacted with anti-TrkA (nerve growth factor
      high-affinity receptor) antibody and bound nerve growth factor. Anti-TrkA
      antibody inhibited the production of O2(-) and binding of the toxin to the
      protein. The toxin induced phosphorylation of 3-phosphoinositide-dependent
      protein kinase 1 (PDK1). K252a, an inhibitor of TrkA receptor, and LY294002, an
      inhibitor of phosphatidylinositol 3-kinase (PI3K), reduced the toxin-induced
      production of O2(-) and phosphorylation of PDK1, but not the formation of DG.
      These inhibitors inhibited the toxin-induced phosphorylation of protein kinase C
      theta (PKCtheta). U73122, a phospholipase C (PLC) inhibitor, and pertussis toxin
      inhibited the toxin-induced generation of O2(-) and formation of DG, but not the
      phosphorylation of PDK1. These observations show that the toxin independently
      induces production of DG through activation of endogenous PLC and phosphorylation
      of PDK1 via the TrkA receptor signaling pathway and that these events
      synergistically activate PKCtheta in stimulating an increase in O2(-). In
      addition, we show the participation of mitogen-activated protein kinase
      associated signaling events via activation of PKCtheta in the toxin-induced
      generation of O2(-).

PMID- 16622227
TI  - Immunoglobulin G antibodies to merozoite surface antigens are associated with
      recovery from chloroquine-resistant Plasmodium falciparum in Gambian children.
AB  - We examined the hypothesis that recovery from uncomplicated malaria in patients
      carrying drug-resistant Plasmodium falciparum is a measure of acquired functional
      immunity and may therefore be associated with humoral responses to candidate
      vaccine antigens. Gambian children with malaria were treated with chloroquine in
      28-day trials, and recovery was defined primarily as the absence of severe
      clinical malaria at any time and absence of parasitemia with fever after 3 days.
      Plasma samples from these children were assayed by enzyme-linked immunosorbent
      assay for immunoglobulin G (IgG) to recombinant merozoite antigens: apical
      membrane antigen 1 (AMA-1) and the 19-kDa C-terminal region of merozoite surface
      protein 1 (MSP-1(19)), including antigenic variants of MSP-1(19) with double and
      triple substitutions. Antigen-specific IgG was more frequent in children who
      recovered, particularly that for MSP-1(19) (age-adjusted odds ratios: 0.32 [95%
      confidence interval, 0.05, 1.87; P = 0.168] for AMA-1, 0.19 [0.03, 1.11; P =
      0.019] for recombinant MSP-1(19), 0.24 [0.04, 1.31; P = 0.032] for the
      recombinant MSP-1(19) double variant, and 0.18 [0.03, 0.97; P = 0.013] for the
      triple variant). IgG titers to MSP-1(19) and to the triple variant were higher in
      plasma samples taken 7 days after chloroquine treatment from children who carried
      resistant parasites but recovered and remained parasite free. Moreover, in
      children who were parasitemic on day 14 or day 28, there was an age-independent
      relationship between parasite density and IgG to both MSP-1(19) and the triple
      variant (coefficients of -0.550 and -0.590 and P values of 0.002 and 0.001,
      respectively). The results validate the use of this approach to identify antigens
      that are associated with protection from malaria.

PMID- 16622228
TI  - The Escherichia coli O157 flagellar regulatory gene flhC and not the flagellin
      gene fliC impacts colonization of cattle.
AB  - A virulent European Escherichia coli O157:H- isolate is nonmotile due to a 12-bp
      deletion in the flagellar regulatory gene flhC. To investigate the contribution
      of flhC in the relationship between E. coli O157:H7 and cattle, we constructed a
      similar flhC regulatory mutant in the well-characterized strain ATCC 43894. There
      was no difference in the growth rate between the wild type and this regulatory
      mutant, but phenotypic arrays showed substrate utilization differences. Survival
      in the bovine gastrointestinal tract and colonization of the rectoanal junction
      mucosa were assessed. Mixtures of both strains were given orally or rectally to
      steers or administered into the rumen of cattle dually cannulated at the rumen
      and duodenum. One day post-oral dose, most rectal/fecal isolates (74%) were the
      regulatory mutant, but by 3 days post-oral dose and throughout the 42-day
      experiment, > or = 80% of the isolates were wild type. Among steers given a
      rectal application of both strains, wild-type isolates were the majority of
      isolates recovered on all days. The regulatory mutant survived better than the
      wild type in both the rumen and duodenum. To test the role of motility, a
      filament mutant (delta fliC) was constructed and similar cattle experiments were
      performed. On all days post-oral dose, the majority of isolates (64% to 98%) were
      the filament mutant. In contrast, both strains were recovered equally post-rectal
      application. Thus, the regulatory mutant survived passage through the bovine
      gastrointestinal tract better than the wild type but failed to efficiently
      colonize cattle, and the requirement of flhC for colonization was not dependent
      on a functional flagellum.

PMID- 16622229
TI  - Intestinal Shiga toxin-producing Escherichia coli bacteria mitigate bovine
      leukemia virus infection in experimentally infected sheep.
AB  - Ruminants often carry gastrointestinal Shiga toxin (Stx)-producing Escherichia
      coli (STEC). Stxs belong to a large family of ribosome-inactivating proteins
      (RIPs), found in many plants and some bacteria. Plant RIPs, secreted into
      extracellular spaces, limit the spread of viruses through plant tissues by
      penetrating and killing virally infected cells. Previously, we showed Stx
      activity against bovine leukemia virus (BLV)-infected cells in vitro and
      hypothesized that STEC bacteria have antiviral activity in ruminant hosts. Here,
      we investigated the impact of STEC on the initial phases of BLV infection in
      sheep. Sheep were treated with biweekly oral doses of E. coli O157:H7 (an STEC)
      or an isogenic stx mutant strain. A different group of sheep were similarly
      treated with five naturally occurring ovine STEC isolates or stx-negative E.
      coli. Intestinal STEC bacteria were enumerated and identified by standard fecal
      culture and DNA hybridization. Oral STEC treatment did not always result in
      carriage of STEC, although many animals consistently presented with >10(4) CFU/g
      feces. BLV viremia was assessed by spontaneous lymphocyte proliferation (SLP) in
      cultures of blood mononuclear cells and by syncytium formation in cocultures of
      the same with F-81 indicator cells. SLP was lower (P < 0.05) and syncytia were
      fewer (P < 0.05) in STEC-treated sheep than in untreated sheep. Both lower SLP
      and fewer syncytia positively correlated with fecal STEC numbers. Average weight
      gain post-BLV challenge was higher in STEC-treated sheep than in untreated sheep
      (P < 0.05). These results support the hypothesis that in ruminants, intestinal
      STEC bacteria have antiviral activity and mitigate BLV-induced disease.

PMID- 16622230
TI  - Cytokine mRNA expression in Mycobacterium ulcerans-infected human skin and
      correlation with local inflammatory response.
AB  - Cytokine mRNA expression in biopsies of Mycobacterium ulcerans-infected human
      tissue was investigated using real-time PCR, and the findings were correlated
      with the clinical stages of disease and histopathologies. A broad range of
      cytokine mRNAs were detected in 16 early nodules and 28 late-stage ulcers,
      including those for the Th1 cytokines tumor necrosis factor alpha (TNF-alpha) and
      gamma interferon (IFN-gamma) and the Th2 cytokine interleukin 10 (IL-10). IFN
      gamma was strongly expressed in both nodules and ulcers, suggesting that a Th1
      response begins early in the disease. There was a significantly higher expression
      of IL-8 and other proinflammatory cytokines in results from 32 biopsies with
      neutrophilia than in those from 12 biopsies without acute inflammation. Ten
      tissue samples containing granulomas showed high mRNA expression for IFN-gamma,
      IL-1beta, IL-12p35, IL-12p40, IL-15, and TNF-alpha relative to 34 tissue samples
      without granulomas. These results suggest that the human immune response to M.
      ulcerans is similar to that seen with some other mycobacteria despite the
      presence of the toxin mycolactone in the tissues.

PMID- 16622231
TI  - Attenuated bioluminescent Brucella melitensis mutants GR019 (virB4), GR024
      (galE), and GR026 (BMEI1090-BMEI1091) confer protection in mice.
AB  - In vivo bioluminescence imaging is a persuasive approach to investigate a number
      of issues in microbial pathogenesis. Previously, we have applied bioluminescence
      imaging to gain greater insight into Brucella melitensis pathogenesis. Endowing
      Brucella with bioluminescence allowed direct visualization of bacterial
      dissemination, pattern of tissue localization, and the contribution of Brucella
      genes to virulence. In this report, we describe the pathogenicity of three
      attenuated bioluminescent B. melitensis mutants, GR019 (virB4), GR024 (galE), and
      GR026 (BMEI1090-BMEI1091), and the dynamics of bioluminescent virulent bacterial
      infection following vaccination with these mutants. The virB4, galE, and BMEI1090
      BMEI1091 mutants were attenuated in interferon regulatory factor 1-deficient (IRF
      1(-/-)) mice; however, only the GR019 (virB4) mutant was attenuated in cultured
      macrophages. Therefore, in vivo imaging provides a comprehensive approach to
      identify virulence genes that are relevant to in vivo pathogenesis. Our results
      provide greater insights into the role of galE in virulence and also suggest that
      BMEI1090 and downstream genes constitute a novel set of genes involved in
      Brucella virulence. Survival of the vaccine strain in the host for a critical
      period is important for effective Brucella vaccines. The galE mutant induced no
      changes in liver and spleen but localized chronically in the tail and protected
      IRF-1(-/-) and wild-type mice from virulent challenge, implying that this mutant
      may serve as a potential vaccine candidate in future studies and that the direct
      visualization of Brucella may provide insight into selection of improved vaccine
      candidates.

PMID- 16622232
TI  - Enterotoxigenicity of mature 45-kilodalton and processed 35-kilodalton forms of
      hemagglutinin protease purified from a cholera toxin gene-negative Vibrio
      cholerae non-O1, non-O139 strain.
AB  - Cholera toxin gene-negative Vibrio cholerae non-O1, non-O139 strain PL-21 is the
      etiologic agent of cholera-like syndrome. Hemagglutinin protease (HAP) is one of
      the major secretory proteins of PL-21. The mature 45-kDa and processed 35-kDa
      forms of HAP were purified in the presence and absence of EDTA from culture
      supernatants of PL-21. Enterotoxigenicities of both forms of HAP were tested in
      rabbit ileal loop (RIL), Ussing chamber, and tissue culture assays. The 35-kDa
      HAP showed hemorrhagic fluid response in a dose-dependent manner in the RIL
      assay. Histopathological examination of 20 microg of purified protease-treated
      rabbit ileum showed the presence of erythrocytes and neutrophils in the upper
      part of the villous lamina propria. Treatment with 40 microg of protease resulted
      in gross damage of the villous epithelium with inflammation, hemorrhage, and
      necrosis. The 35-kDa form of HAP, when added to the lumenal surface of rat ileum
      loaded in an Ussing chamber, showed a decrease in the intestinal short-circuit
      current and a cell rounding effect on HeLa cells. The mature 45-kDa form of HAP
      showed an increase in intestinal short-circuit current in an Ussing chamber and a
      cell distending effect on HeLa cells. These results show that HAP may play a role
      in the pathogenesis of PL-21.

PMID- 16622233
TI  - Accessory gene regulator locus of Staphylococcus intermedius.
AB  - The accessory gene regulator (agr) locus, a candidate system for the regulation
      of the production of virulence factors in Staphylococcus intermedius, has been
      characterized. Using PCR-based genome walking, we have obtained the first
      complete sequence (3,436 bp) of the accessory gene regulator (agr) gene in this
      organism. Sequence analysis of the agr gene has identified five open reading
      frames (ORFs), agrB, agrD, agrC, agrA, and hld. The translated ORF contained
      amino acid motifs characteristic of the response regulator and histidine protein
      kinase signal transducer of the classic two-component regulatory system.
      Sequencing of the agrD PCR products amplified from DNA from 20 different isolates
      has facilitated detection of genetic variation in the putative autoinducing
      peptide (AIP) within the agr gene of S. intermedius, revealing the presence of at
      least three agr specificity groups within this species. Classification of the agr
      gene from S. intermedius was supported by phylogenetic analysis. Real-time PCR
      also revealed that the effector molecule of the agr system, RNAIII, was regulated
      in an autocrine manner in S. intermedius and demonstrated positive correlation
      with the temporal gene expression patterns of luk and entC. Transcription of
      RNAIII was also dependent on self secreted cues. Cyclic self and nonself peptides
      were synthesized on the basis of the novel AIPs produced by S. intermedius, which
      lack the cysteine necessary to form the thiolactone ring in analogous peptides
      from Staphylococcus aureus and Staphylococcus epidermidis. Experiments with these
      synthetic cyclic peptides indicated that self peptides led to up-regulation of
      RNAIII--findings in support of the assumption that activation of the agr gene is
      initiated by growth- and species-specific factors generated during bacterial
      growth.

PMID- 16622234
TI  - Characterization of MspA, an immunogenic autotransporter protein that mediates
      adhesion to epithelial and endothelial cells in Neisseria meningitidis.
AB  - A novel putative autotransporter protein (NMB1998) was identified in the
      available genomic sequence of meningococcal strain MC58 (ET-5; ST-32). The mspA
      gene is absent from the genomic sequences of meningococcal strain Z2491 (ET-IV;
      ST-4) and the gonococcal strain FA1090. An orthologue is present in the
      meningococcal strain FAM18 (ET-37; ST-11), but the sequence contains a premature
      stop codon, suggesting that the protein may not be expressed in this strain. MspA
      is predicted to be a 157-kDa protein with low cysteine content, and it exhibits
      36 and 33% identity to the meningococcal autotransporter proteins immunoglobulin
      A1 (IgA1) protease and App, respectively. Search of the Pfam database predicts
      the presence of IgA1 protease and autotransporter beta-barrel domains. MspA was
      cloned, and a recombinant protein of the expected size was expressed and after
      being affinity purified was used to raise rabbit polyclonal monospecific
      antiserum. Immunoblot studies showed that ca. 125- and 95-kDa fragments of MspA
      are secreted in meningococcal strain MC58, which are absent from the isogenic
      mutant. Secretion of MspA was shown to be modified in an AspA isogenic mutant. A
      strain survey showed that MspA is expressed by all ST-32 and ST-41/44 (lineage 3)
      strains, but none of the ST-8 (A4) strains examined. Sera from patients
      convalescing from meningococcal disease were shown to contain MspA-specific
      antibodies. In bactericidal assays, anti-MspA serum was shown to kill the
      homologous strain (MC58) and another ST-32 strain. Escherichia coli-expressing
      recombinant MspA was shown to adhere to both human bronchial epithelial cells and
      brain microvascular endothelial cells.

PMID- 16622235
TI  - In vivo selection for Neisseria gonorrhoeae opacity protein expression in the
      absence of human carcinoembryonic antigen cell adhesion molecules.
AB  - The neisserial opacity (Opa) proteins are phase-variable, antigenically distinct
      outer membrane proteins that mediate adherence to and invasion of human cells. We
      previously reported that Neisseria gonorrhoeae Opa protein expression appeared to
      be selected for or induced during experimental murine genital tract infection.
      Here we further defined the kinetics of recovery of Opa variants from the lower
      genital tracts of female mice and investigated the basis for this initial
      observation. We found that the recovery of different Opa phenotypes from mice
      appears cyclical. Three phases of infection were defined. Following intravaginal
      inoculation with primarily Opa- gonococci, the majority of isolates recovered
      were Opa+ (early phase). A subsequent decline in the percentage of Opa+ isolates
      occurred in a majority of mice (middle phase) and was followed by a reemergence
      of Opa+ variants in mice that were infected for longer than 8 days (late phase).
      We showed the early phase was due to selection for preexisting Opa+ variants in
      the inoculum by constructing a chloramphenicol-resistant (Cm(r)) strain and
      following Cm(r) Opa+ populations mixed with a higher percentage of Opa- variants
      of the wild-type (Cm(s)) strain. Reciprocal experiments (Opa- Cm(r) gonococci
      spiked with Opa+ Cm(s) bacteria) were consistent with selection of Opa+ variants.
      Based on the absence in mice of human carcinoembryonic antigen cell adhesion
      molecules, the major class of Opa protein adherence receptors, we conclude the
      observed selection for Opa+ variants early in infection is not likely due to a
      specific adherence advantage and may be due to Opa-mediated evasion of innate
      defenses.

PMID- 16622236
TI  - Nonclassical pathway of Pseudomonas aeruginosa DNA-induced interleukin-8
      secretion in cystic fibrosis airway epithelial cells.
AB  - Pseudomonas aeruginosa is a critical colonizer of the respiratory tract in cystic
      fibrosis. The chronic infections with this microorganism contribute to excessive
      inflammation and progressive lung damage in cystic fibrosis patients. The full
      repertoire of Pseudomonas products that promote inflammation in the cystic
      fibrosis lung is not known. Here we show that P. aeruginosa DNA released from the
      bacterium, but not human DNA from epithelial cells or Escherichia coli DNA,
      displays proinflammatory properties and induces human respiratory epithelial
      cells to secrete interleukin-8 (IL-8), a key chemokine causing excessive
      neutrophil infiltration in the cystic fibrosis lung. IL-8 secretion was not due
      to an increase in NF-kappaB- or activator protein-1-dependent IL-8 promoter
      transcription, but instead depended on p38 and Erk mitogen-activated protein
      kinases. No secretion of IL-8 was observed using conventional Toll-like receptor
      9 ligands (CpG oligonucleotides), although it could be demonstrated that parts of
      the Toll-like receptor 9-signaling pathway were functional, since class B and C
      CpG oligonucleotide ligands stimulated production of RANTES chemokine. The IL-8
      secretion in response to P. aeruginosa DNA was decreased by treatments that
      inhibit acidification of intracellular organelles, using chloroquine, a pH
      neutralizing compound, or bafilomycin A1, an inhibitor of vacuolar H+-ATPase.
      These data indicate that DNA released from P. aeruginosa during chronic
      infections may significantly contribute to the proinflammatory processes in
      cystic fibrosis. Our findings also show that treatments with drugs diminishing
      organellar acidification may reduce the inflammatory response in cystic fibrosis.

PMID- 16622237
TI  - Deletion of the Mycobacterium tuberculosis resuscitation-promoting factor Rv1009
      gene results in delayed reactivation from chronic tuberculosis.
AB  - Approximately one-third of the human population is latently infected with
      Mycobacterium tuberculosis, comprising a critical reservoir for disease
      reactivation. Despite the importance of latency in maintaining M. tuberculosis in
      the human population, little is known about the mycobacterial factors that
      regulate persistence and reactivation. Previous in vitro studies have implicated
      a family of five related M. tuberculosis proteins, called resuscitation promoting
      factors (Rpfs), in regulating mycobacterial growth. We studied the in vivo role
      of M. tuberculosis rpf genes in an established mouse model of M. tuberculosis
      persistence and reactivation. After an aerosol infection with the M. tuberculosis
      Erdman wild type (Erdman) or single-deletion rpf mutants to establish chronic
      infections in mice, reactivation was induced by administration of the nitric
      oxide (NO) synthase inhibitor aminoguanidine. Of the five rpf deletion mutants
      tested, one (deltaRv1009) exhibited a delayed reactivation phenotype, manifested
      by delayed postreactivation growth kinetics and prolonged median survival times
      among infected animals. Immunophenotypic analysis suggested differences in
      pulmonary B-cell responses between Erdman- and deltaRv1009-infected mice at
      advanced stages of reactivation. Analysis of rpf gene expression in the lungs of
      Erdman-infected mice revealed that relative expression of four of the five rpf
      like genes was diminished at late times following reactivation, when bacterial
      numbers had increased substantially, suggesting that rpf gene expression may be
      regulated in a growth phase-dependent manner. To our knowledge, deltaRv1009 is
      the first M. tuberculosis mutant to have a specific defect in reactivation
      without accompanying growth defects in vitro or during acute infection in vivo.

PMID- 16622238
TI  - Mixed strain infections and strain-specific protective immunity in the rodent
      malaria parasite Plasmodium chabaudi chabaudi in mice.
AB  - Important to malaria vaccine design is the phenomenon of "strain-specific"
      immunity. Using an accurate and sensitive assay of parasite genotype, real-time
      quantitative PCR, we have investigated protective immunity against mixed
      infections of genetically distinct cloned "strains" of the rodent malaria
      parasite Plasmodium chabaudi chabaudi in mice. Four strains of P. c. chabaudi,
      AS, AJ, AQ, and CB, were studied. One round of blood infection and drug cure with
      a single strain resulted in a partial reduction in parasitemia, compared with
      levels for naive mice, in challenge infections with mixed inocula of the
      immunizing (homologous) strain and a heterologous strain. In all cases, the
      numbers of blood-stage parasites of each genotype were reduced to similar
      degrees. After a second, homologous round of infection and drug cure followed by
      challenge with homologous and heterologous strains, the parasitemias were reduced
      even further. In these circumstances, moreover, the homologous strain was reduced
      much faster than the heterologous strain in all of the combinations tested. That
      the immunity induced by a single infection did not show "strain specificity,"
      while the immunity following a second, homologous infection did, suggests that
      the "strain-specific" component of protective immunity in malaria may be
      dependent upon immune memory. The results show that strong, protective immunity
      induced by and effective against malaria parasites from a single parasite species
      has a significant "strain-specific" component and that this immunity operates
      differentially against genetically distinct parasites within the same infection.

PMID- 16622239
TI  - Role of the Porphyromonas gingivalis InlJ protein in homotypic and heterotypic
      biofilm development.
AB  - The oral pathogen Porphyromonas gingivalis expresses a homolog of the internalin
      family protein InlJ. Inactivation of inlJ reduced monospecies biofilm formation
      by P. gingivalis. In contrast, heterotypic P. gingivalis-Streptococcus gordonii
      biofilm formation was enhanced in the InlJ-deficient mutant. The results indicate
      a nuanced role for InlJ in regulating biofilm accumulations of P. gingivalis.

PMID- 16622240
TI  - The hbhA gene of Mycobacterium tuberculosis is specifically upregulated in the
      lungs but not in the spleens of aerogenically infected mice.
AB  - We report that hbhA is differentially regulated during Mycobacterium tuberculosis
      infection. Upregulation was observed in epithelial cell infection but not in
      macrophage infection and in the lungs but not in the spleens of infected mice,
      and it was greater during the early steps of infection, when bacilli disseminate
      from the site of primary infection.

PMID- 16622241
TI  - The posttranscriptional regulator RsmA plays a role in the interaction between
      Pseudomonas aeruginosa and human airway epithelial cells by positively regulating
      the type III secretion system.
AB  - Posttranscriptional regulation of certain virulence-related genes in Pseudomonas
      aeruginosa is brought about by RsmA, a small RNA-binding protein. During
      interaction with airway epithelial cells, RsmA promoted actin depolymerization,
      cytotoxicity, and anti-internalization of P. aeruginosa by positively regulating
      the virulence-associated type III secretion system.

PMID- 16622242
TI  - Bgp, a secreted glycosaminoglycan-binding protein of Borrelia burgdorferi strain
      N40, displays nucleosidase activity and is not essential for infection of
      immunodeficient mice.
AB  - Bgp, one of the surface-localized glycosaminoglycan-binding proteins of the Lyme
      disease spirochete, Borrelia burgdorferi, exhibited nucleosidase activity.
      Infection of SCID mice with B. burgdorferi strain N40 mutants harboring a
      targeted insertion in bgp and apparently retaining all endogenous plasmids
      revealed that Bgp is not essential for colonization of immunocompromised mice.

PMID- 16622243
TI  - Role for RpoS but not RelA of Legionella pneumophila in modulation of phagosome
      biogenesis and adaptation to the phagosomal microenvironment.
AB  - The induction of virulence traits by Legionella pneumophila at the post
      exponential phase has been proposed to be triggered by the stringent response
      mediated by RelA, which triggers RpoS. We show that L. pneumophila rpoS but not
      relA is required for early intracellular survival and replication within human
      monocyte-derived macrophages and Acanthamoeba polyphaga. In addition, L.
      pneumophila rpoS but not relA is required for expression of the pore-forming
      activity. We provide evidence that RpoS plays a role in the modulation of
      phagosome biogenesis and in adaptation to the phagosomal microenvironment. Thus,
      there is no functional link between the stringent response and RpoS in the
      pathogenesis of L. pneumophila.

PMID- 16622244
TI  - Cleavage of the N-linked oligosaccharide from the surfaces of Chlamydia species
      affects infectivity in the mouse model of lung infection.
AB  - Previous studies determined that the Chlamydia glycan contains a high-mannose
      oligosaccharide, which is involved in attachment and infectivity of the organism,
      and that removal of the glycan decreases infectivity in vitro. The present study
      demonstrates that treatment of the organism with N-glycanase decreases or ablates
      infectivity in vivo.

PMID- 16622245
TI  - Evidence that the BBA68 protein (BbCRASP-1) of the Lyme disease spirochetes does
      not contribute to factor H-mediated immune evasion in humans and other animals.
AB  - BBA68 (BbCRASP-1) of the Lyme disease spirochetes binds human factor H (FH) and
      FH-like protein 1 (FHL-1). Here we assess transcription of the BBA68 gene and
      production of BBA68 in infected mice and humans using real-time reverse
      transcriptase PCR and immunoblotting. The species specificity of FH binding to
      BBA68 was also tested. The data suggest that BBA68 does not play an important
      role in immune evasion in animals.

PMID- 16622246
TI  - Plasmodium falciparum parasites expressing pregnancy-specific variant surface
      antigens adhere strongly to the choriocarcinoma cell line BeWo.
AB  - Placenta-sequestering Plasmodium falciparum parasites causing pregnancy
      associated malaria express pregnancy-specific variant surface antigens
      (VSA(PAM)). We report here that VSA(PAM)-expressing patient isolates adhere
      strongly to the choriocarcinoma cell line BeWo and that the BeWo line can be used
      to efficiently select for VSA(PAM) expression in vitro.

PMID- 16622247
TI  - The anti-Candida vaccine based on the recombinant N-terminal domain of Als1p is
      broadly active against disseminated candidiasis.
AB  - We have previously shown that vaccination with a vaccine based on the recombinant
      N-terminal domain of Als1p (rAls1p-N) protected BALB/c mice against disseminated
      infection caused by a single strain of Candida albicans (A. S. Ibrahim, B. J.
      Spellberg, V. Avenissian, Y. Fu, S. G. Filler, and J. E. Edwards, Jr., Infect.
      Immun. 73:999-1005, 2005, and B. J. Spellberg, A. S. Ibrahim, V. Avenissian, S.
      G. Filler, C. Myers, Y. Fu, and J. E. Edwards, Jr., Infect. Immun. 73:6191-6193,
      2005). Here we show that the rAls1p-N vaccine also improves survival of outbred
      mice from disseminated candidiasis and that it is active against multiple
      virulent strains of C. albicans and non-C. albicans spp.

PMID- 16622248
TI  - A fungicidal monoclonal antibody protects against murine invasive candidiasis.
AB  - Mice infected by Candida albicans and treated with monoclonal antibody C7
      survived longer than saline-treated animals. A prozone-like effect was observed.
      The in vitro candidacidal activity of macrophages was strongly enhanced when C.
      albicans was opsonized by C7 and complete murine serum was present.

PMID- 16622249
TI  - Multiple chromosomal loci for the babA gene in Helicobacter pylori.
AB  - Helicobacter pylori babA encodes an outer membrane protein that binds to
      fucosylated Lewis b blood group antigen. We analyzed a panel of 35 H. pylori
      strains and identified three possible chromosomal loci for babA. There was a
      significant association between the presence of babA and the presence of cagA (P
      = 0.0001). Phylogenetic analysis of babA alleles revealed two divergent families
      of signal sequences. Among 17 strains in which an intact in-frame babA allele was
      identified, 10 expressed a detectable BabA protein. Expression of a BabA protein
      and the Lewis b-binding phenotype were not dependent on the chromosomal locus of
      babA. These data indicate that there is marked heterogeneity among H. pylori
      strains in babA genetic content and BabA expression.

PMID- 16622250
TI  - Requirement of histidine kinases HP0165 and HP1364 for acid resistance in
      Helicobacter pylori.
AB  - In this study, we investigated a potential requirement of two-component signal
      transduction systems for acid resistance in Helicobacter pylori. In comparison to
      a wild-type strain, isogenic strains with null mutations in either HP0165 or
      HP1364 histidine kinases were impaired in their ability to grow at pH 5.0. The
      growth of complemented mutant strains was similar to that of the wild-type
      strain. H. pylori DNA array analyses and transcriptional reporter assays
      indicated that acid-responsive gene transcription was altered in the HP0165 and
      HP1364 null mutant strains compared to the parental wild-type strain. These
      results indicate that intact HP0165 and HP1364 histidine kinases are required for
      acid resistance in H. pylori.

PMID- 16622251
TI  - Role of the histone-like nucleoid structuring protein in colonization, motility,
      and bile-dependent repression of virulence gene expression in Vibrio cholerae.
AB  - Bile-mediated repression of virulence gene expression is relieved in a Vibrio
      cholerae hns mutant. The mutant also exhibited reduced motility due to lower flrA
      expression, higher in vivo production of the virulence factors, and lower
      colonization efficiency. The colonization defect of the mutant was due to low
      FlrA production.

PMID- 16622252
TI  - The iron efflux protein ferroportin regulates the intracellular growth of
      Salmonella enterica.
AB  - We investigated the influence of the macrophage iron exporter ferroportin and its
      ligand hepcidin on intracellular Salmonella growth. Elevated ferroportin
      expression inhibited bacterial multiplication; hepcidin-induced ferroportin down
      regulation enhanced it. Expression analysis of iron-responsive Salmonella genes
      indicated ferroportin-mediated iron deprivation. These results demonstrate a role
      for ferroportin in antimicrobial resistance.

PMID- 16622253
TI  - Administration of antibody to the lung protects mice against pneumonic plague.
AB  - Intratracheal delivery of aerosolized monoclonal antibodies with specificity for
      Yersinia pestis LcrV and F1 antigens protected mice in a model of pneumonic
      plague. These data support the utility of inhaled antibodies as a fast-acting
      postexposure treatment for plague.

PMID- 16622254
TI  - Modification of a mammalian cell protein in the presence of [32P-adenylate]NAD:
      evidence for ADP ribosylation activity associated with Helicobacter pylori.
AB  - Culture filtrates from Helicobacter pylori promote the transfer of the radiolabel
      from [32P-adenylate]NAD to one or more heat-labile factors within extracts
      prepared from several mammalian cell lines, with the predominate radiolabeled
      species exhibiting an apparent molecular mass of greater than 130 kDa. Our
      results suggest that several H. pylori strains release a factor that ADP
      ribosylates a mammalian target protein.

PMID- 16622255
TI  - Proteomic analysis of ischemia-reperfusion injury upon human liver
      transplantation reveals the protective role of IQGAP1.
AB  - Ischemia-reperfusion injury (IRI) represents a major determinant of liver
      transplantation. IRI-induced graft dysfunction is related to biliary damage,
      partly due to a loss of bile canaliculi (BC) integrity associated with a dramatic
      remodeling of actin cytoskeleton. However, the molecular mechanisms associated
      with these events remain poorly characterized. Using liver biopsies collected
      during the early phases of organ procurement (ischemia) and transplantation
      (reperfusion), we characterized the global patterns of expression and
      phosphorylation of cytoskeleton-related proteins during hepatic IRI. This
      targeted functional proteomic approach, which combined protein expression pattern
      profiling and phosphoprotein enrichment followed by mass spectrometry analysis,
      allowed us to identify IQGAP1, a Cdc42/Rac1 effector, as a potential regulator of
      actin cytoskeleton remodeling and maintenance of BC integrity. Cell fractionation
      and immunohistochemistry revealed that IQGAP1 expression and localization were
      affected upon IRI and related to actin reorganization. Furthermore using an IRI
      model in human hepatoma cells, we demonstrated that IQGAP1 silencing decreased
      the basal level of actin polymerization at BC periphery, reflecting a defect in
      BC structure coincident with reduced cellular resistance to IRI. In summary, this
      study uncovered new mechanistic insights into the global regulation of IRI
      induced cytoskeleton remodeling and led to the identification of IQGAP1 as a
      regulator of BC structure. IQGAP1 therefore represents a potential target for the
      design of new organ preservation strategies to improve transplantation outcome.

PMID- 16622256
TI  - In utero exposure to chemotherapy: effect on cardiac and neurologic outcome.

PMID- 16622257
TI  - Gefitinib therapy in advanced bronchioloalveolar carcinoma: Southwest Oncology
      Group Study S0126.
AB  - PURPOSE: Advanced bronchioloalveolar carcinoma (BAC) is a distinct subtype of non
      small-cell lung cancer (NSCLC) for which there is currently no optimal therapy.
      Based on preclinical and clinical data suggesting relevance of the epidermal
      growth factor receptor (EGFR) axis in BAC, the Southwest Oncology Group initiated
      a phase II trial (S0126) to evaluate the EGFR tyrosine kinase inhibitor gefitinib
      in chemotherapy-naive and chemotherapy-pretreated patients with advanced BAC.
      METHODS: A total of 136 eligible and assessable patients (101 untreated, 35
      previously treated) received gefitinib 500 mg daily until progression or
      prohibitive toxicity. RESULTS: The median age was 68.0 years (range, 34.3 to
      88.6); 51% were female; 89% had a performance status (PS) of 0% or 1% and 11% had
      a PS of 2. The Response Evaluation Criteria in Solid Tumors response rate was
      17%, with 6% complete responses (CRs) among 69 previously untreated patients with
      measurable disease, and 9% with no CRs among 22 pretreated patients. Median
      survival was 13 months for both chemo-naive (95% CI, 8 to 18) and previously
      treated patients (95% CI, 6 to 17). Overall survival at 3 years was 23% (95% CI,
      14% to 32%). Toxicity consisted mainly of rash and diarrhea, but 2% of patients
      died of presumed interstitial lung disease. Exploratory subset analyses revealed
      improved survival among women (P = .031), patients developing a rash (P = .003),
      never-smokers (P = .061), and patients with a PS of 0 or 1 (P = .015).
      CONCLUSION: Gefitinib is an active agent in advanced stage BAC. Several subsets
      demonstrate significantly improved clinical outcomes.

PMID- 16622258
TI  - Gene expression signature predicting pathologic complete response with
      gemcitabine, epirubicin, and docetaxel in primary breast cancer.
AB  - PURPOSE: Primary systemic therapy (PST) with gemcitabine (G), epirubicin (E), and
      docetaxel (Doc) has resulted in a pathologic complete response (pCR) in 26% of
      primary breast cancer patients. This study was aimed at the identification of a
      gene expression signature in diagnostic core biopsy tissue samples that predicts
      pCR. PATIENTS AND METHODS: Core biopsy samples from patients with operable
      primary breast cancer, T2-4N0-2M0, enrolled onto two phase I and II trials
      evaluating GEDoc (n = 48) and GE sequentially followed by Doc (GEsDoc; n = 52) as
      PST were snap frozen and subjected to RNA expression profiling. A signature
      predicting pCR was discovered in the training set (GEsDoc) applying a support
      vector machine algorithm, and performance of this classifier was validated on the
      independent test set (GEDoc) by receiver operator characteristics analysis.
      RESULTS: We identified a signature consisting of 512 genes, which was enriched in
      genes involved in transforming growth factor beta and RAS-mediated signaling
      pathways, that predicts pCR with a sensitivity of 78%, a specificity of 90%, and
      an overall accuracy of 88% (95% CI, 75% to 95%). Apart from our signature, only
      HER2 overexpression was an independent predictor of pCR in multivariate analysis.
      CONCLUSION: In conclusion, our gene expression signature allows prediction of pCR
      to PST containing G, E, and Doc with unprecedented high overall accuracy and
      robustness.

PMID- 16622259
TI  - Assessment of tumor necrosis factor alpha blockade as an intervention to improve
      tolerability of dose-intensive chemotherapy in cancer patients.
AB  - PURPOSE: Maintaining dose-intensity with chemotherapeutic agents is hindered by a
      number of adverse effects including asthenia/fatigue. Tumor necrosis factor (TNF)
      is one of the cytokines responsible for the fatigue and cachexia associated with
      malignancies. We used etanercept (TNF-decoy receptor) to maintain dose-intensity
      of weekly docetaxel. PATIENTS AND METHODS: Initially, 12 patients with advanced
      malignancies were randomly assigned to either docetaxel 43 mg/m2 weekly alone
      (cohort A) or the same docetaxel dose plus etanercept 25 mg subcutaneously twice
      weekly (cohort B). Subsequently, higher doses of docetaxel in combination with
      etanercept were evaluated. Pharmacokinetics (PKs), nuclear factor-kappa B (NF
      kappaB) activation, and intracellular cytokines levels were measured. Patients
      completed weekly questionnaires quantifying asthenia/fatigue. RESULTS: Twenty
      nine of 36 intended docetaxel doses during the first cycle were delivered in
      cohort A, and 35 of 36 doses were delivered in cohort B (P = .055). Three cohort
      B patients received additional cycles in the absence of disease progression or
      severe toxicity, whereas no patients from cohort A received additional cycles.
      Escalation to docetaxel 52 mg/m2 weekly with etanercept resulted in neutropenia,
      not fatigue, as the limiting adverse effect, and the addition of filgrastim
      permitted the maintenance of dose-intensity in additional patients. Patients
      randomly selected to receive etanercept/docetaxel self-reported less fatigue (P <
      .001), and docetaxel PKs show no relevant influence of etanercept. NF-kappaB
      activation and increased expression of TNF-alpha were associated with increments
      in docetaxel dose. Antitumor activity was noticed exclusively in patients
      receiving etanercept. CONCLUSION: The addition of etanercept is safe and had no
      impact on docetaxel concentrations. The significant improvement in tolerability
      and the trend toward preservation of dose-intensity suggests further exploration
      of TNF blockade as an adjunct to cancer therapies.

PMID- 16622260
TI  - Factors associated with participation in breast cancer treatment clinical trials.
AB  - PURPOSE: It is well established that recruitment to clinical trials (CTs) is
      difficult and time consuming. This article reports on factors related to CT
      participation among women who were invited to participate in a CT for breast
      cancer. PATIENTS AND METHODS: Breast cancer patients who were eligible for a CT
      were identified by 16 different cancer centers. After their invitation to
      participate in a trial, patients who were undecided about participation in a CT
      were recruited into the present study at that time. After a patient made a
      decision about trial participation, a telephone interview was conducted to assess
      knowledge of CTs, perceived benefits and drawbacks of CTs, and personal factors
      affecting the women's decision regarding participation. RESULTS: A total of 208
      patients participated in the study. Fifty-eight percent of the patients decided
      to participate in a trial. Logistic regression analyses showed that the factors
      best explaining participation were trial phase, perceived drawbacks, time and
      travel considerations, therapeutic benefit of trial, and physician
      recommendation. Participation rates were similar for both phase I and phase III
      trials. However, a higher percentage of women recruited to phase II trials
      accepted. CONCLUSION: This study suggests that reducing drawbacks of CT
      participation, particularly travel time, and improving physician communication of
      trials are needed to increase trial participation.

PMID- 16622261
TI  - Immediate or deferred androgen deprivation for patients with prostate cancer not
      suitable for local treatment with curative intent: European Organisation for
      Research and Treatment of Cancer (EORTC) Trial 30891.
AB  - PURPOSE: This study (EORTC 30891) attempted to demonstrate equivalent overall
      survival in patients with localized prostate cancer not suitable for local
      curative treatment treated with immediate or deferred androgen ablation. PATIENTS
      AND METHODS: We randomly assigned 985 patients with newly diagnosed prostate
      cancer T0-4 N0-2 M0 to receive androgen deprivation either immediately (n = 493)
      or on symptomatic disease progression or occurrence of serious complications (n =
      492). RESULTS: Baseline characteristics were well balanced in the two groups.
      Median age was 73 years (range, 52 to 81). At a median follow-up of 7.8 years,
      541 of 985 patients had died, mostly of prostate cancer (n = 193) or
      cardiovascular disease (n = 185). The overall survival hazard ratio was 1.25 (95%
      CI, 1.05 to 1.48; noninferiority P > .1) favoring immediate treatment, seemingly
      due to fewer deaths of nonprostatic cancer causes (P = .06). The time from
      randomization to progression of hormone refractory disease did not differ
      significantly, nor did prostate-cancer specific survival. The median time to the
      start of deferred treatment after study entry was 7 years. In this group 126
      patients (25.6%) died without ever needing treatment (44% of the deaths in this
      arm). CONCLUSION: Immediate androgen deprivation resulted in a modest but
      statistically significant increase in overall survival but no significant
      difference in prostate cancer mortality or symptom-free survival. This must be
      weighed on an individual basis against the adverse effects of life-long androgen
      deprivation, which may be avoided in a substantial number of patients with a
      deferred treatment policy.

PMID- 16622262
TI  - Dermoscopy improves accuracy of primary care physicians to triage lesions
      suggestive of skin cancer.
AB  - PURPOSE: Primary care physicians (PCPs) constitute an appropriate target for new
      interventions and educational campaigns designed to increase skin cancer
      screening and prevention. The aim of this randomized study was to determine
      whether the adjunct of dermoscopy to the standard clinical examination improves
      the accuracy of PCPs to triage lesions suggestive of skin cancer. PATIENTS AND
      METHODS: PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training
      course in skin cancer detection and dermoscopic evaluation, and were randomly
      assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a
      16-month period, 73 physicians evaluated 2,522 patients with skin lesions who
      attended their clinics and scored individual lesions as benign or suggestive of
      skin cancer. All patients were re-evaluated by expert dermatologists at clinics
      for pigmented lesions. Referral accuracy of both PCP groups was calculated by
      their scores, which were compared to those tabulated for dermatologists. RESULTS:
      Referral sensitivity, specificity, and positive and negative predictive values
      were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and
      79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant
      differences were found in terms of sensitivity and negative predictive value (P =
      .002 and P = .004, respectively). Histopathologic examination of equivocal
      lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye
      observation and only six by PCPs using dermoscopy (P = .002). CONCLUSION: The use
      of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin
      cancer without increasing the number of unnecessary expert consultations.

PMID- 16622263
TI  - Pharmacogenetic profiling and clinical outcome of patients with advanced gastric
      cancer treated with palliative chemotherapy.
AB  - PURPOSE: To investigate whether polymorphisms with putative influence on
      fluorouracil/cisplatin activity are associated with clinical outcomes of patients
      with advanced gastric cancer (AGC). PATIENTS AND METHODS: Peripheral blood
      samples from 175 prospectively enrolled AGC patients treated with
      fluorouracil/cisplatin palliative chemotherapy were used for genotyping 13
      polymorphisms in nine genes (TS, MTHFR, XPD, ERCC1, XRCC1, XRCC3, GSTPI, GSTTI,
      GSTMI). Genotypes were correlated to response and survival. RESULTS: The overall
      response rate was 41%, the median progression-free survival (PFS) was 24 weeks
      (range, 4 to 50 weeks), and the median overall survival (OS) was 39 weeks (range,
      8 to 72+ weeks). Chemoresistance and poor survival were significantly associated
      with TS 5'-UTR 3G-genotype (2R/3G, 3C/3G, 3G/3G) and GSTP1 105 A/A homozygous
      genotype. Sixty-one patients (35%) did not show any of these risk genotypes
      (group 0), 57 patients (32.5%) showed one of the two risk genotypes (group 1),
      and 57 patients (32.5%) showed both risk genotypes (group 2). Median PFS and OS
      in group 0 patients were 32 weeks (range, 8 to 50 weeks) and 49 weeks (range, 18
      to 72+ weeks), respectively. Group 1 and group 2 patients showed significantly
      worse PFS (median, 26 weeks [range, 6 to 44 weeks] and 14 weeks [range, 4 to 38
      weeks], respectively) and worse OS (median, 39 weeks [range, 10 to 58 weeks] and
      28 weeks [range, 8 to 56 weeks]), respectively, than group 0 patients. This
      adverse effect was retained in multivariate analysis. CONCLUSION: Specific
      polymorphisms may influence clinical outcomes of AGC patients. Selecting
      palliative chemotherapy on the basis of pretreatment genotyping may represent an
      innovative strategy that warrants prospective studies.

PMID- 16622264
TI  - Phase II study of capecitabine, oxaliplatin, and erlotinib in previously treated
      patients with metastastic colorectal cancer.
AB  - PURPOSE: To investigate the combination of erlotinib, capecitabine, and
      oxaliplatin in patients who were previously treated for metastatic colorectal
      cancer. PATIENTS AND METHODS: Patients were eligible if they had metastatic
      colorectal cancer that progressed, were intolerant to first-line chemotherapy, or
      had disease recurrence within 1 year of adjuvant therapy for early-stage disease.
      Each 21-day cycle consisted of daily oral erlotinib at 150 mg, oral capecitabine
      at 1,000 mg/m2 (reduced to 750 mg/m2 after the first 13 patients) twice a day on
      days 1 to 14, and intravenous oxaliplatin at 130 mg/m2 on day 1. RESULTS: Thirty
      two patients were enrolled onto this phase II study. By intention-to-treat
      analyses, eight patients (25%) experienced a partial response and 14 patients
      (44%) had stable disease for at least 12 weeks. The median progression-free
      survival was 5.4 months and the median overall survival was 14.7 months. These
      results were essentially unchanged when limited to the cohort of patients (78%)
      who received prior irinotecan for metastatic colorectal cancer. Most common grade
      3 to 4 toxicities included diarrhea (38%), nausea/emesis (19%), fatigue (16%),
      dehydration (16%), and dermatitis (13%); grade 3 or 4 toxicities were reduced
      with a lower starting dose of capecitabine. CONCLUSION: The combination of
      capecitabine, oxaliplatin, and erlotinib seems to have promising activity against
      metastatic colorectal cancer in patients who received prior chemotherapy, with a
      relatively higher response rate and progression-free survival compared with
      previous reports of either infusional FU, leucovorin, and oxaliplatin or
      capecitabine and oxaliplatin in similar patient populations.

PMID- 16622265
TI  - Phase II study of gemcitabine and oxaliplatin in combination with bevacizumab in
      patients with advanced hepatocellular carcinoma.
AB  - PURPOSE: Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis.
      Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the
      potential benefits of targeting the vascular endothelial growth factor pathway
      with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define
      efficacy and toxicity profiles in HCC patients. PATIENTS AND METHODS: Eligible
      patients had pathologically proven measurable unresectable or metastatic HCC. For
      cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on
      day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was
      administered on days 1 and 15, gemcitabine 1,000 mg/m2 was administered as a dose
      rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and
      16. RESULTS: Thirty-three patients were enrolled and 30 patients were assessable
      for efficacy. The objective response rate was 20%, and 27% of patients had stable
      disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not
      available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7
      to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and
      48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3
      to 4 toxicities included leukopenia/neutropenia, transient elevation of
      aminotransferases, hypertension, and fatigue. CONCLUSION: GEMOX-B could be safely
      administered with close monitoring and had moderate antitumor activity for
      patients with advanced HCC. The high 6-month PFS rate is encouraging, and this
      regimen is worthy of further investigation.

PMID- 16622266
TI  - Sensorineural hearing loss after radiotherapy and chemoradiotherapy: a single,
      blinded, randomized study.
AB  - PURPOSE: The synergistic ototoxicity of radiation and cisplatin (CDDP) has not
      been adequately studied. This study investigated whether the use of concurrent
      and postradiotherapy CDDP in patients with nasopharyngeal carcinoma (NPC)
      resulted in a difference in postradiotherapy sensorineural hearing when compared
      with the use of radiotherapy alone. PATIENTS AND METHODS: Newly diagnosed
      patients were randomly assigned to the radiotherapy or chemoradiotherapy groups.
      Bone conduction hearing thresholds were performed before treatment and at 1 week,
      6 months, 1 year, and 2 years after completion of radiotherapy. Statistical
      analysis was performed using the Mann-Whitney U test. RESULTS: Hearing thresholds
      averaged over 0.5, 1, and 2 kHz were found to be poorer in the chemoradiotherapy
      group (58 patients) compared with the radiotherapy group (57 patients) at 1 year
      (P = .001) and 2 years (P = .03) after radiotherapy. Hearing thresholds at 4 kHz
      were significantly worse for patients in the chemoradiotherapy arm at all of the
      postradiotherapy time points studied and were more severely affected than the
      thresholds at lower speech frequencies. In the radiotherapy group, deterioration
      of median hearing thresholds, which occurred in the immediate post-treatment
      period, improved within the first year but deteriorated again at 2 years. In the
      chemoradiotherapy group, median hearing threshold deterioration, which started
      immediately after radiotherapy, stabilized by 1 year. CONCLUSION: Patients with
      NPC who received radiotherapy and concurrent/adjuvant chemotherapy using CDDP
      experienced greater sensorineural hearing loss compared with patients treated
      with radiotherapy alone, especially to high-frequency sounds in the speech range.
      Normal inner ear tissue tolerance, which was once defined only for radiotherapy
      patients alone, should be redefined in chemoradiotherapy patients.

PMID- 16622267
TI  - Chemokine receptor CCR6 expression level and liver metastases in colorectal
      cancer.
AB  - PURPOSE: The liver is the primary organ of metastasis in colorectal cancer (CRC).
      Chemokine receptor CCR6 is expressed on a subset of T cells and is associated
      with their migration into the liver. This study was performed to analyze a
      possible association between CCR6 expressed by primary CRC and liver metastases.
      PATIENTS AND METHODS: CCR6 expression levels were evaluated by immunohistology in
      64 CRC primary tumor specimens. Twenty-four of 64 patients had synchronous liver
      metastases. Evaluation of immunostaining was performed semiquantitatively by
      visual assessment and quantitatively by digital image analysis (DIA). Multiple
      logistic regression analysis was performed to assess relevant parameters for
      liver metastases. RESULTS: CCR6 expression was verified in all 64 primary tumor
      specimens with considerable variations in intensity; 21 tumors (33%) demonstrated
      weak CCR6 staining, 32 (50%) demonstrated intermediate staining, and 11 (17%)
      demonstrated strong staining. Quantitative assessment by DIA showed an up to 5
      log difference in CCR6 values. CCR6 staining was significantly stronger in tumor
      cells compared with adjacent colon epithelial cells (P < .0005). Multiple
      logistic regression analysis, controlling for age, sex, tumor stage, nodal
      status, pathologic grade, and preoperative carcinoembryonic antigen levels,
      revealed that CCR6 staining in the primary tumor was independently associated
      with the presence of liver metastases (odds ratio = 2.1; P = .002). CONCLUSION:
      The association between expression level of CCR6 in primary CRC and synchronous
      liver metastases suggests that CCR6 and its ligand may be involved in the
      metastatic spread to the liver. Therefore, CCR6 may be a potential target for
      specific therapeutic interventions.

PMID- 16622268
TI  - Phase II study of clofarabine in pediatric patients with refractory or relapsed
      acute lymphoblastic leukemia.
AB  - PURPOSE: To evaluate the efficacy and safety of clofarabine, a novel
      deoxyadenosine analog, in pediatric patients with refractory or relapsed acute
      lymphoblastic leukemia (ALL). PATIENTS AND METHODS: In a phase II, open-label,
      multicenter study, 61 pediatric patients with refractory or relapsed ALL received
      clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days, every 2 to 6
      weeks. The median age was 12 years (range, 1 to 20 years), and the median number
      of prior regimens was three (range, two to six regimens). RESULTS: The response
      rate was 30%, consisting of seven complete remissions (CR), five CRs without
      platelet recovery (CRp), and six partial remissions. Remissions were durable
      enough to allow patients to proceed to hematopoietic stem-cell transplantation
      (HSCT) after clofarabine. Median CR duration in patients who did not receive HSCT
      was 6 weeks, with four patients maintaining CR or CRp for 8 weeks or more (8+,
      12, 37+, and 48 weeks) on clofarabine therapy alone. The most common adverse
      events of grade > or = 3 were febrile neutropenia, anorexia, hypotension, and
      nausea. CONCLUSION: Clofarabine is active as a single agent in pediatric patients
      with multiple relapsed or refractory ALL. The toxicity profile is as expected in
      this heavily pretreated patient population. Studies exploring rational
      combinations of clofarabine with other agents are ongoing in an effort to
      maximize clinical benefit.

PMID- 16622269
TI  - Educating undergraduate medical students about oncology: a literature review.
AB  - PURPOSE: This article is a review of the literature regarding teaching oncology
      to undergraduate medical students. METHODS: MEDLINE, Psychinfo, ERIC, TIMELIT,
      EMBASE, CINAHL and the Cochrane CENTRAL Register of Controlled Trials (CENTRAL)
      were searched, using the search terms cancer, oncology, education, undergraduate,
      and teaching. RESULTS: The main findings can be summarized as follows: the
      involvement of patients in teaching is popular with students and portfolio
      learning is a successful way of involving patients; the use of standardized
      patients to teach breast examination improves students' performance in clinical
      assessment; the use of silicone models to teach breast examination improves
      students' sensitivity for detecting breast lumps; computer aided learning modules
      have a role, but are not superior to other types of learning; learning about
      cancer screening and prevention increases students' knowledge, improves their
      self rated skills, and changes their behavior; and cancer patients have an
      important role to play in teaching undergraduate communication skills.
      CONCLUSION: We have found 48 articles on undergraduate teaching in oncology.
      Oncology teachers should consider adopting the evidence based approaches outlined
      in this review, and there should be more emphasis on educational research within
      the field of oncology.

PMID- 16622270
TI  - Recommendations from an international expert panel on the use of neoadjuvant
      (primary) systemic treatment of operable breast cancer: an update.
AB  - Neoadjuvant (primary systemic) treatment is the standard treatment for locally
      advanced breast cancer and a standard option for primary operable disease.
      Because of new treatments and new understandings of breast cancer, however,
      recommendations published in 2003 regarding neoadjuvant treatment for operable
      disease required updating. Therefore, a second international panel of
      representatives of a number of breast cancer clinical research groups was
      convened in September 2004 to update these recommendations. As part of this
      effort, data published to date were reviewed critically and indications for
      neoadjuvant treatment were newly defined.

PMID- 16622271
TI  - Large B-cell lymphoma masquerading as acute leukemia.

PMID- 16622272
TI  - Acute lung injury associated with vinorelbine.

PMID- 16622273
TI  - Laryngeal obstruction and hoarseness associated with Rosai-Dorfman disease.

PMID- 16622274
TI  - Aromatase inhibitor withdrawal response in metastatic breast cancer.

PMID- 16622275
TI  - New issues on cetuximab mechanism of action in epidermal growth factor receptor
      negative colorectal cancer: the role of vascular endothelial growth factor.

PMID- 16622276
TI  - Childhood nonrhabdomyosarcoma soft tissue sarcomas are not adult-type tumors.

PMID- 16622277
TI  - Is it time to abandon microsatellite instability as a pre-screen for selecting
      families for mutation testing for mismatch repair genes?

PMID- 16622278
TI  - Overestimating the influence of the 1999 WHO classification of lung tumors on
      survival in bronchioloalveloar carcinoma.

PMID- 16622279
TI  - Are we cautious enough when we interpret results of randomized but underpowered
      comparisons?

PMID- 16622280
TI  - Role of selenium supplementation and heat stress on trehalose and glutathione
      content in Saccharomyces cerevisiae.
AB  - The role of selenium (Se) supplementation on glutathione, a potent intracellular
      redox buffer, and trehalose, a well-known stress protectant molecule, was
      studied. The amount of glutathione decreased significantly while that of
      trehalose showed a minor decrease in the cells grown in Se-supplemented medium.
      After heat shock, glutathione content diminished further, whereas that of
      trehalose increased significantly in control and Se-supplemented cells. These
      findings suggest the importance of trehalose as an antioxidant molecule.

PMID- 16622281
TI  - Adenoviral vectors: a promising tool for gene therapy.
AB  - Gene therapy is a promising tool for treatment of the human diseases that cannot
      be cured by rational therapies, and its primary success depends on suitable
      vectors to deliver therapeutic genes. Adenoviruses (Ads) are among the most
      commonly used vectors for gene therapy, second only to retroviruses. During the
      last decade, remarkable progress has been made in the development of Ad vectors
      and in the understanding of the toxicity related to the Ad vector system. Ad
      vector has certain advantages such as high transduction efficiency for different
      quiescent and dividing cell types and high levels of short-term expression to
      provide therapeutic benefits. However, researchers are facing the challenges
      associated with tissue-specific targeting of vectors and the vector-mediated
      immunogenicity. This review mainly focuses on the studies that have employed
      methods to improve Ad vectors and reduce viral toxicity for different
      applications. These methods include minimization or elimination of viral genes,
      retargeting of vector to the tissue of interest, and generation of
      immunocompromised recombinant vectors that lead to safer use of Ad vector systems
      that improve persistence of transgene expression. Moreover, the therapeutic
      applications of Ad vectors for liver-targeted gene therapy, suicide gene therapy,
      delivery of small interfering RNA, and production of recombinant vaccine under
      regulated conditions used in clinical trials are discussed.

PMID- 16622282
TI  - Enzymatic synthesis of prebiotic oligosaccharides.
AB  - Prebiotic oligosaccharides are nondigestible carbohydrates that can be obtained
      by enzymatic synthesis. Glucosyltransferases can be used to produce these
      carbohydrates through an acceptor reaction synthesis. When maltose is the
      acceptor a trisaccharide composed of one maltose unit and one glucose unit linked
      by an alpha-1,6-glycosidic bond (panose) is obtained as the primer product of the
      dextransucrase acceptor reaction. In this work, panose enzymatic synthesis was
      evaluated by a central composite experimental design in which maltose and sucrose
      concentration were varied in a wide range of maltose/sucrose ratios in a batch
      reactor system. A partially purified enzyme was used in order to reduce the
      process costs, because enzyme purification is one of the most expensive steps in
      enzymatic synthesis. Even using high maltose/sucrose ratios, dextran and higher
      oligosaccharide formation were not avoided. The results showed that intermediate
      concentrations of sucrose and high maltose concentration resulted in high panose
      productivity with low dextran and higher-oligosaccharide productivity.

PMID- 16622283
TI  - Pretreatment of corn stover by low-liquid ammonia recycle percolation process.
AB  - A pretreatment method using aqueous ammonia was investigated with the intent of
      minimizing the liquid throughput. This process uses a flowthrough packed column
      reactor (or percolation reactor). In comparison to the ammonia recycle
      percolation (ARP) process developed previously in our laboratory, this process
      significantly reduces the liquid throughput to one reactor void volume in packed
      bed (2.0-4.7 mL of liquid/g of corn stover) and, thus, is termed low-liquid ARP
      (LLARP). In addition to attaining short residence time and reduced energy input,
      this process achieves 59-70% of lignin removal and 48-57% of xylan retention.
      With optimum operation of the LLARP to corn stover, enzymatic digestibilities of
      95, 90, and 86% were achieved with 60, 15, and 7.5 filter paper units/g of
      glucan, respectively. In the simultaneous saccharification and fermentation test
      of the LLARP samples using Saccharomyces cerevisiae (NREL-D5A), an ethanol yield
      of 84% of the theoretical maximum was achieved with 6% (w/v) glucan loading. In
      the simultaneous saccharification and cofermentation (SSCF) test using
      recombinant Escherichia coli (KO11), both the glucan and xylan in the solid were
      effectively utilized, giving an overall ethanol yield of 109% of the theoretical
      maximum based on glucan, a clear indication that the xylan content was converted
      into ethanol. The xylooligomers existing in the LLARP effluent were not
      effectively hydrolyzed by cellulase enzyme, achieving only 60% of digestibility.
      SSCF of the treated corn stover was severely hampered when the substrate was
      supplemented with the LLARP effluent, giving only 56% the overall yield of
      ethanol. The effluent appears to significantly inhibit cellulase and microbial
      activities.

PMID- 16622284
TI  - Inactivation of Botrytis cinerea during thermophilic composting of greenhouse
      tomato plant residues.
AB  - The effectiveness of in-vessel thermophilic composting on the inactivation of
      Botrytis cinerea was evaluated. The bioreactor operated on an infected mixture of
      tomato plant residues, wood shavings, and municipal solid compost (1:1.5:0.28).
      Tap water and urea were added to adjust the moisture content and C:N ratio to 60%
      and 30:1, respectively. Used cooking oil was added as a bioavailable carbon
      source to compensate for heat losses from the system and extend the thermophilic
      composting stage. The controlled thermophilic composting process was successful
      in inactivating B. cinerea. During all experiments, the average reactor
      temperature increased gradually, reaching its peak after 31 h of operation.
      Temperatures in the range of 62.6-63.9 degrees C were maintained during the
      thermophilic stage by the intermittent addition of used cooking oil. The results
      of the enzyme-linked immunosorbent assay test indicated that the initial
      concentration of B. cinerea in the compost samples (14.6 mug of dried mycelium/g
      of compost) was reduced to 12.9, 8.8, and 2.4 mu/g after 24, 48, and 72 h of
      thermophilic composting, respectively. Plating assay indicated that the mold was
      completely inactivated in samples after 48 h of thermophilic composting. No
      significant reduction in B. cinerea was observed during the transient phase
      (first 30 h of rising temperature) because the temperature reached the lethal
      level of 55 degrees C after 23 h, thus allowing only 7 h of exposure to
      temperatures higher than 55 degrees C during this phase. The relatively short
      time required for complete inactivation of B. cinerea was achieved by maintaining
      a constant high temperature and a uniform distribution of temperature and
      extending the duration of the thermophilic stage by the addition of the proper
      amount of bioavailable carbon (used cooking oil).

PMID- 16622285
TI  - Expression and purification of a mutant of human interleukin-2 in Pichia
      pastoris.
AB  - Interleukin (IL)-2 is a pharmacologically important cytokine secreted by T
      lymphocytes. Recombinant IL-2 (rIL-2) has been modified and produced in many
      systems. Mass production of rIL-2 is the prerequisite for its wide application.
      Using a site-directed mutagenesis strategy, we first generated a gene coding for
      a new type of mutant of human IL-2 (MhIL-2), in which we replaced the cysteine
      125 in human IL-2 with alanine, the leucine-18 with methionine, and the leucine
      19 with serine. Then we investigated the possibility of its production of MhIL-2
      in a Pichia pastoris system. High-level secreted expression of MhIL-2 was
      achieved by methanol induction. When purified with ultrafiltration, cation
      exchange chromatography, and Sephadex G100 gel filtration, about 100 mg of MhIL-2
      with high purity was obtained from 1 L of ferment supernatant. Biologic activity
      assay revealed that the purified recombinant protein displayed increased activity
      on proliferation of IL-2-dependent CTLL-2 cells. These results suggest that MhIL
      2 is an improved IL-2 mutant that might hold great promise for clinical use, and
      that P. pastoris is an excellent system for the mass production of biologically
      active hIL-2.

PMID- 16622286
TI  - Obesity.

PMID- 16622287
TI  - Diet modification for treatment and prevention of obesity.
AB  - The obesity epidemic is best explained by global lifestyle alterations favoring
      weight gain in a susceptible population. The consumption of calorically dense
      foods, increased portion sizes, and a decrease in workplace and leisure physical
      activity most likely accounts for the increase in overweight and obesity
      worldwide. The cornerstone of overweight and obesity therapy is dietary
      intervention, but unfortunately most patients eventually regain the weight lost
      through diet alone. The search for a macronutrient composition that may enhance
      and help maintain weight loss has brought an abundance of fad diets into the lay
      literature. According to the available data, weight loss and maintenance of
      weight loss are dictated by total caloric intake, and not by macronutrient
      composition. There is epidemiologic data linking sugar-sweetened beverages to
      adult and childhood obesity, and an inverse relationship between dairy intake and
      overweight and obesity has also been observed. More research is needed to
      elucidate mechanisms explaining these relationships. Further research should
      focus on permanent lifestyle changes that may reverse this growing epidemic. This
      review will focus on current practices for the dietary management of obesity and
      to promote weight maintenance.

PMID- 16622289
TI  - Obesity, weight loss, and vascular function.
AB  - Obesity promotes the development of several major cardiovascular risk factors.
      Moreover, excess adiposity may play a direct role in initiating atherosclerosis
      as fat cells are capable of affecting the systemic vasculature through a variety
      of mechanisms. Recent studies demonstrate that obesity per se may impair vascular
      endothelial function. This is important as endothelial dysfunction is a key
      factor in the pathogenesis of atherosclerosis and in triggering acute ischemic
      events. At present, few studies have determined the beneficial impact of weight
      loss on cardiovascular outcomes and mortality. However, several experiments have
      demonstrated that weight loss can lead to improvements in endothelial function, a
      validated surrogate marker of cardiovascular risk. The mechanisms whereby weight
      loss restores vascular health are likely multifactorial. However, the relative
      importance of reduced adiposity versus the specific dietary regimens prescribed,
      the role of concomitant exercise, and the direct effect of medications remain
      unclear. Several other unresolved issues such as the longevity of improvement,
      the amount of weight loss required, and whether the improvement in endothelial
      function actually translates into a reduction in cardiovascular events also
      remain to be determined. Nevertheless, lifestyle changes that lead to weight
      reduction are able to improve vascular function in overweight adults.

PMID- 16622288
TI  - Surgical treatment of obesity.
AB  - The surgical treatment of obesity has existed for over 50 yr. Surgical options
      have evolved from high-risk procedures infrequently performed, to safe, effective
      procedures increasingly performed. The operations used today provide significant
      durable weight loss, resolution or marked improvement of obesity-related
      comorbidities, and enhanced quality of life for the majority of patients. The
      effect of bariatric surgery on the neurohormonal regulation of energy homeostasis
      is not fully understood. Despite its effectiveness, less than 1% of obese
      patients are treated surgically. The perception that obesity surgery is unsafe
      remains a deterrent to care.

PMID- 16622290
TI  - Energy metabolism and oxidative stress: impact on the metabolic syndrome and the
      aging process.
AB  - Aging can be defined as a progressive decline in the ability of the organism to
      resist stress, damage, and disease. Although there are currently over 300
      theories to explain the aging phenomenon, it is still not well understood why
      organisms age and why the aging process can vary so much in speed and quality
      from individual to individual. The oxidative stress hypothesis is one of the
      prevailing theories of aging. This theory states that free radicals produced
      during cellular respiration damage lipids, proteins, and DNA thereby accelerating
      the aging process and increasing disease risk. Under normal conditions, the
      electron transport chain is the primary producer of the superoxide anion, which
      is precursor to other highly reactive species such as hydrogen peroxide and the
      hydroxyl radical. Oxidative stress accumulates when prooxidants overwhelm the
      antioxidant defense mechanisms. This is dependent on a number of factors
      including free radical production, susceptibility of tissue to stress, and
      strength of the defense and repair system. Oxidative stress has been implicated
      in a number of chronic disease states usually grouped under the umbrella of the
      metabolic syndrome and is thought to contribute to the aging process. It has been
      hypothesized that the production of free radicals is dependent on resting
      metabolic rate and this may have an impact on the aging process. However, other
      factors, such as mitochondrial function, may be important in the production of
      free radicals and the subsequent effect on aging and disease states.

PMID- 16622292
TI  - Central nervous system biogenic amine targets for control of appetite and energy
      expenditure.
AB  - Central biogenic amine systems have long been studied for their effects on
      feeding behavior, energy balance, and maintenance of body weight. Those
      monoaminergic systems that use dopamine (DA), norepinephrine (NE), and serotonin
      (5-hydroxytryptamine, 5-HT) as neurotransmitters have been the main targets of
      study. A number of antiobesity medications that affect monoaminergic activity
      have appeared on the market and/or in clinical trials. Early examples of such
      agents are the so-called CNS stimulants, e.g., the amphetamines, phentermine,
      ephedrine, etc. These agents release monoamines from neuronal stores, and their
      antiobesity activity seems to be tied most closely to their ability to release
      NE. Inhibitors of neuronal reuptake of NE or 5-HT have been shown to reduce
      feeding and weight gain both preclinically and clinically. However, the magnitude
      and sustainability of such effects in clinical trials has generally not been
      great enough to register or label these agents for the treatment of obesity.
      Sibutramine, however, is an exception. This compound is metabolized in vivo to
      produce metabolites that have varying degrees of inhibition of NE, 5-HT, and/or
      DA uptake. Sibutramine is the only drug affecting monoaminergic systems currently
      approved for the long-term control of obesity. Research continues on serotonergic
      and histaminergic systems to determine if targets such as the 5-HT2C and H3
      receptors may be suitable for developing antiobesity agents. Because the clinical
      antiobesity effects of monoaminergic drugs have been modest, future directions
      include looking at combinations of different monoaminergic mechanisms and/or
      combinations of monoaminergic drugs with non-monoaminergic mechanisms.

PMID- 16622291
TI  - Hypothalamic regulatory pathways and potential obesity treatment targets.
AB  - With an ever-growing population of obese people as well as comorbidities
      associated with obesity, finding effective weight loss strategies is more
      imperative than ever. One of the challenges in curbing the obesity crisis is
      designing successful strategies for long-term weight loss and weight-loss
      maintenance. Currently, weight-loss strategies include promotion of therapeutic
      lifestyle changes (diet and exercise), pharmacological therapy, and bariatric
      surgery. This review focuses on several pharmacological targets that activate
      central nervous system pathways that normally limit food intake and body weight.
      Though it is likely that no single therapy will prove effective for everyone,
      this review considers several recent pre-clinical targets, and several compounds
      that have been in human clinical trials.

PMID- 16622293
TI  - Gut hormones ghrelin, PYY, and GLP-1 in the regulation of energy balance
      [corrected] and metabolism.
AB  - The first hormone discovered in the gastrointestinal tract was secretin, isolated
      from duodenal mucosa. Some years later, two additional gastrointestinal hormones,
      gastrin and cholecystokinin (CCK), were discovered, but it was not until the
      1970s that gastrointestinal endocrinology studies became more prevalent,
      resulting in the discovery of many more hormones. Here, we examine the role of
      gut hormones in energy balance regulation and their possible use as
      pharmaceutical targets for obesity.

PMID- 16622294
TI  - Insulin resistance and improvements in signal transduction.
AB  - Type 2 diabetes and obesity are common metabolic disorders characterized by
      resistance to the actions of insulin to stimulate skeletal muscle glucose
      disposal. Insulin-resistant muscle has defects at several steps of the insulin
      signaling pathway, including decreases in insulin-stimulated insulin receptor and
      insulin receptor substrate-1 tyrosine phosphorylation, and phosphatidylinositol 3
      kinase (PI 3-kinase) activation. One approach to increase muscle glucose disposal
      is to reverse/improve these insulin-signaling defects. Weight loss and
      thiazolidinediones (TZDs) improve glucose disposal, in part, by increasing
      insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation and PI 3
      kinase activity. In contrast, physical training and metformin improve whole-body
      glucose disposal but have minimal effects on proximal insulin-signaling steps. A
      novel approach to reverse insulin resistance involves inhibition of the stress
      activated protein kinase Jun N-terminal kinase (JNK) and the protein tyrosine
      phosphatases (PTPs). A different strategy to increase muscle glucose disposal is
      by stimulating insulin-independent glucose transport. AMP-activated protein
      kinase (AMPK) is an enzyme that works as a fuel gauge and becomes activated in
      situations of energy consumption, such as muscle contraction. Several studies
      have shown that pharmacologic activation of AMPK increases glucose transport in
      muscle, independent of the actions of insulin. AMPK activation is also involved
      in the mechanism of action of metformin and adiponectin. Moreover, in the
      hypothalamus, AMPK regulates appetite and body weight. The effect of AMPK to
      stimulate muscle glucose disposal and to control appetite makes it an important
      pharmacologic target for the treatment of type 2 diabetes and obesity.

PMID- 16622295
TI  - Adipocyte-derived hormones, cytokines, and mediators.
AB  - Adipose tissue is responsive to both central and peripheral metabolic signals and
      is itself capable of secreting a number of proteins. These adipocyte-specific or
      enriched proteins, termed adipokines, have been shown to have a variety of local,
      peripheral, and central effects. These secreted proteins, which include tumor
      necrosis factor (TNF)-alpha, resistin, IL-6, IL-8, acylation-stimulating protein
      (ASP), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1) ("bad"
      adipokines) and leptin, adiponectin ("good" adipokines) seem to play important
      regulatory roles in a variety of complex processes, including fat metabolism,
      feeding behavior, hemostasis, vascular tone, energy balance, and insulin
      sensitivity, but none is without controversy regarding its respective mechanism
      and scope of action. The present review is focused on the effects of free fatty
      acids and a restricted number of adipokines, which have been implicated in
      vascular (angiotensinogen, PAI-1) and energy and glucose homeostasis (ASP,
      TNFalpha, IL-6, resistin, leptin, adiponectin).

PMID- 16622296
TI  - Modulation of fatty acid metabolism as a potential approach to the treatment of
      obesity and the metabolic syndrome.
AB  - Increased de novo lipogenesis and reduced fatty acid oxidation are probable
      contributors to adipose accretion in obesity. Moreover, these perturbations have
      a role in leading to non-alcoholic steatohepatitis, dyslipidemia, and insulin
      resistance--via "lipotoxicity"-related mechanisms. Research in this area has
      prompted an effort to evaluate several discrete enzymes in these pathways as
      targets for future therapeutic intervention. Acetyl-CoA carboxylase 1 (ACC1) and
      ACC2 regulate fatty acid synthesis and indirectly control fatty acid oxidation
      via a key product, malonyl CoA. Based on mouse genetic and preclinical
      pharmacologic evidence, inhibition of ACC1 and/or ACC2 may be a useful approach
      to treat obesity and metabolic syndrome. Similarly, available data suggest that
      inhibition of other enzymes in this pathway, including fatty acid synthase,
      stearoyl CoA desaturase, and diacylglycerol acytransferase 1, will have
      beneficial effects. AMP-activated protein kinase is a master regulator of
      nutrient metabolism, which controls several aspects of lipid metabolism.
      Activation of AMPK in selected tissues is also a potential therapeutic approach.
      Inhibition of hormone-sensitive lipase is another possible approach. The
      rationale for modulating the activity of these enzymes and their relative merits
      (and downsides) as possible therapeutic targets are further discussed.

PMID- 16622298
TI  - Epidemiology, trends, and morbidities of obesity and the metabolic syndrome.
AB  - Obesity has been described as an epidemic because of the rapid increase in the
      number of overweight and obese individuals over the past 20 yr. This increasing
      prevalence of obesity is a worldwide phenomenon affecting both children and
      adults. The metabolic syndrome is a constellation of central adiposity, impaired
      fasting glucose, elevated blood pressure, and dyslipidemia (high triglyceride and
      low HDL cholesterol). When three of these five criteria are present, the risk of
      cardiovascular disease and diabetes is increased 1.5- to 2-fold. As body weight,
      expressed as the BMI, rises, there are a number of other diseases that are
      associated with it. First, life span is shortened and the risk of sudden death
      increases. Second, the risk of diabetes, gall bladder disease, hypertension,
      heart disease, osteoarthritis, sleep apnea, and certain forms of cancer also
      increase.

PMID- 16622297
TI  - Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity.
AB  - Excessive glucocorticoid exposure (Cushing's syndrome) results in increased
      adiposity associated with dysmetabolic features (including insulin resistance,
      hyperlipidaemia, and hypertension). Circulating cortisol levels are not elevated
      in idiopathic obesity, although cortisol production and clearance are increased.
      However, tissue glucocorticoid exposure may be altered independently of
      circulating levels by 11beta-hydroxysteroid dehydrogenase type 1 (11HSD1), an
      enzyme which generates active glucocorticoid within tissues, including in adipose
      tissue. Transgenic overexpression of 11HSD1 in mice causes obesity. In human
      obesity, 11HSD1 is altered in a tissue-specific manner with reduced levels in
      liver but elevated levels in adipose, which may lead to glucocorticoid receptor
      activation and contribute to the metabolic phenotype. The reasons for altered
      11HSD1 in obesity are not fully understood. Although some polymorphisms have been
      demonstrated in intronic and upstream regions of the HSD11B1 gene, the functional
      significance of these is not clear. In addition, there is mounting evidence that
      11HSD1 may be dysregulated secondarily to factors that are altered in obesity,
      including substrates for metabolism, hormones, and inflammatory mediators. 11HSD1
      is a potential therapeutic target for the treatment of the metabolic syndrome.
      11HSD1 knockout mice are protected from diet-induced obesity and associated
      metabolic dysfunction. Although many specific inhibitors of 11HSD1 have now been
      developed, and published data support their efficacy in the liver to reduce
      glucose production, their efficacy in enhancing insulin sensitivity in adipose
      tissue remains uncertain. The therapeutic potential of 11HSD1 in human obesity
      therefore remains highly promising but as yet unproven.

PMID- 16622299
TI  - Cyclin-dependent kinase inhibitor gene polymorphisms in pituitary gigantism.

PMID- 16622300
TI  - Mitogen-activated protein kinase is involved in the progesterone-mediated
      induction of baboon glycodelin.
AB  - In the human and non-human primate the major secretory product of the uterine
      glandular epithelial cells is glycodelin. The expression of glycodelin is
      associated with elevated progesterone levels as its production peaks during the
      late luteal phase of the menstrual cycle and in early pregnancy. Consistent with
      our previous studies, we found that the majority of the progestin responsiveness
      of the baboon glycodelin promoter was retained in the -20+48 region, a region
      devoid of progestin- and Sp1-response elements. Using serial 5' and 3' deletions
      of 10 basepairs of the promoter within the pGL3Basic vector, we identified the 5'
      and 3' limits required for progestin responsiveness as -22 and +18, respectively.
      When the same regions were cloned into the pGL3Promoter vector, a construct that
      contains the heterologous SV40 promoter, progestin did not enhance expression.
      Mutation of the DNA binding domain of the progesterone receptor, which disrupts
      its ability to activate the progesterone response element, does not obliterate
      its ability to induce expression via the baboon glycodelin promoter. Inhibitors
      of protein tyrosine kinases, genistein and AG18, blocked the progestin-mediated
      induction as did an inhibitor of MEK, PD98059, but not an inhibitor of p38 MAP
      kinase, SB202190. These findings imply that glycodelin induction in response to
      progestins involves a nongenomic mechanism through the ERK1/2 branch of the MAP
      kinase pathway. The ultimate target may be a factor involved in the initiation of
      glycodelin gene transcription.

PMID- 16622301
TI  - The estrogenic effect of Pueraria mirifica on gonadotrophin levels in aged
      monkeys.
AB  - We investigated the effect of Pueraria mirifica (PM) on gonadotrophin and
      estradiol levels in aged animals; nine menopausal cynomolgus monkeys were divided
      into three groups. Each group (n = 3) was fed with 10, 100, and 1000 mg/d of PM
      for 90 d. PM-10 induced the decrease of follicle stimulating hormone (FSH) levels
      on d 15-90 in one out of three monkeys. PM-100 and PM-1000 decreased FSH levels
      of all monkeys throughout the treatment period. After the treatment period, FSH
      levels continued to decrease for 5 and 10-20 d in PM-100 and PM-1000,
      respectively, and the levels rebounded in all groups thereafter. PM-10 decreased
      luteinizing hormone (LH) levels throughout the treatment period in one out of
      three monkeys and returned to the pretreatment levels immediately after stopping
      treatment. PM-100 and PM-1000 prominently decreased LH levels between d 10 and 90
      during treatment and persisted until d 15-25 and d 20-30 for PM-100 and PM-1000,
      respectively, during the post-treatment period. Serum LH levels rebounded after
      returning to pre-treatment levels in a dose-dependent manner. Estradiol levels
      tended to decrease during the treatment period in all groups. The daily feeding
      of PM suppressed gonadotrophin levels in aged menopausal monkeys based on dose.
      Moreover, they can be recovered, and there is a direct correlation between dosage
      and recovery time. PM may be effective as an alternative medicine in menopausal
      women because the effects are not permanent.

PMID- 16622302
TI  - Effects of gender difference on cardiac myocyte dysfunction in streptozotocin
      induced diabetic rats.
AB  - The main characteristics of type 1 diabetic cardiomyopathy include depressed
      contractility and altered electrophysiological properties in ventricular
      myocytes. The goal of the present study was to determine the potential influence
      of gender in the diabetes-induced pathogenesis of ventricular myocyte function.
      Diabetes in both male and female rats was induced by a single intravenous
      injection of streptozotocin (STZ). Diabetic rats exhibited hyperglycemia and
      reduced body weight gain in both male and female groups. Neither contractile
      profiles nor activity of three types of K+ channels of ventricular myocytes was
      significantly different between nondiabetic male and female rats. Ventricular
      myocytes isolated from diabetic rats exhibited significant depression in cell
      contraction and relaxation, which was associated with depression of intracellular
      Ca2+ ([Ca2+]i) transient. The degrees of contractile depression were comparable
      in ventricular myocytes obtained from both male and female diabetic rats.
      Similarly, diabetes depressed three types of outward K+ currents (Ito, Ik, and
      Iss) to the same extent in both gender myocytes. These data demonstrate that in
      this animal model of diabetes, gender difference in cardiac myocyte functions was
      eliminated.

PMID- 16622303
TI  - Effects of pioglitazone vs glibenclamide on postprandial increases in glucose and
      triglyceride levels and on oxidative stress in Japanese patients with type 2
      diabetes.
AB  - To investigate the relationship between insulin resistance, postprandial
      hyperglycemia, postprandial hyperlipidemia, and oxidative stress in type 2
      diabetes, changes in postprandial glucose, triglyceride, and nitrotyrosine levels
      vs baseline after diet loading were examined in type 2 diabetic patients given
      pioglitazone (PG) or glibenclamide (GB). Twenty-four outpatients with type 2
      diabetes treated with oral PG for 6 mo (BMI, 26.3 +/- 0.9; HbA1c, 8.2 +/- 0.2%)
      and 10 type 2 diabetic patients treated with GB (BMI, 27.4 +/- 1.6; HbA1c, 8.1 +/
      0.2%) at our institutions were compared. These patients were given meal
      tolerance tests (MTT; each consisting of energy 400 kcal, protein 8.7 g, fat 22.4
      g, carbohydrate 41 g) before and 6 mo after administration of either agent. PG
      produced a significant decrease in FPG, HbA1c, HOMA-R, and TG levels in the
      subjects compared to baseline. In contrast, GB significantly decreased FPG and
      HbA1c levels, while not affecting HOMA-R and TG values. While PG produced a
      significant increase in LPL, HDL-cholesterol, and adiponectin levels, GB did not
      affect these values. At MTT 6 mo after PG administration, insulin levels before
      and 4 h after MTT, free fatty acid (FFA) levels 1, 2, and 4 h after MTT, glucose,
      TG, and RLP-TG levels before and 1, 2, 4, and 6 h after MTT were significantly
      decreased compared to baseline. At MTT 6 mo after GB administration, while a
      significant decrease in fasting and 2 h, postprandial glucose values compared to
      baseline MTT levels was observed, fasting and postprandial TG and RLP-TG levels
      remained unchanged compared to baseline. After 6 mo of PG and GB administration,
      serum nitrotyrosine levels before and after MTT were significantly decreased
      compared to baseline in both groups, while the decrease in nitrotyrosine levels
      before and after MTT was more marked in the subjects given PG. Our study results
      suggest that PG suppresses increases in postprandial glucose and TG levels, and
      improves insulin resistance; and, in addition, that PG may have a favorable
      impact on oxidative stress in type 2 diabetic patients.

PMID- 16622304
TI  - Differences in the pathology of the metabolic syndrome with or without visceral
      fat accumulation: a study in pre-diabetic Japanese middle-aged men.
AB  - To elucidate the role of visceral fat accumulation in the metabolic syndrome,
      differences in the pathology of the metabolic syndrome with or without visceral
      fat accumulation were investigated. A total of 472 prediabetic Japanese men (mean
      age, 47.5 +/- 7.2 yr) with impaired fasting glycemia (IFG) levels of 110-125
      mg/dL were eligible for participation in the study. The study subjects were
      divided into the following four groups, and intergroup comparisons were made:
      group I without visceral fat area [VFA] > or = 100 cm2 but presenting with fewer
      than two other risk factors (i.e., TG > or =150 mg/dL, HDL-C < 40 mg/dL, BP > or
      = 130/ > or = 85 mmHg, or FPG > or = 110 mg/dL) (n = 231); group II without VFA
      of > or = 100 cm2 but presenting with three or more other risk factors (n = 57);
      group III with VFA of > or = 100 cm2 accompanied by FPG 110 mg/dL alone (n = 27);
      and group IV with VFA > or =100 cm2 and two or more other risk factors (n = 157).
      The prevalence of patients who had three or more risk factors with or without VFA
      > or = 100 cm2 was 45.3% (214 out of 472 patients), while that of those with VFA
      > or = 100 cm2 who had two or more other risk factors was 33% (157 out of 472
      patients). Group II had significantly higher VFA values than group I (p < 0.05),
      and group IV had significantly higher VFA values than group II (p < 0.001). While
      no significant differences in HOMA-R values were seen between groups I and II,
      these values were significantly higher in group IV compared to groups I and II (p
      < 0.001 and p < 0.05, respectively). Furthermore, group IV showed significantly
      higher 2-h insulin levels after glucose loading compared to group I (p < 0.001).
      While no significant differences were seen between groups II and IV, insulin
      levels tended to be higher in group IV. Adiponectin levels showed an incremental
      fall in VFA from group I through groups II and III to group IV. Groups III and IV
      showed significantly lower adiponectin levels compared to group I (p < 0.05, p <
      0.001, respectively); and group IV showed significantly lower adiponectin levels
      than group II (p < 0.05). A logistic regression analysis using VFA, TG and HDL-C,
      and BP as explanatory variables showed that the relative risk for high HOMAR
      values were 2.65 (p < 0.001) for patients with VFA > or =100 cm2; 1.64 (p < 0.05)
      for those with TG > or = 150 mg/dL and HDL < 40 mg/dL; and 1.79 (p < 0.01) for
      those with BP > or = 130/ > or = 85 mmHg. These findings demonstrate that the
      degree of insulin resistance and the risk of arteriosclerosis vary depending on
      whether or not the metabolic syndrome accompanied by a clustering of risk factors
      has visceral fat accumulation as an underlying pathology, strongly suggesting a
      crucial role for visceral fat accumulation in the metabolic syndrome.

PMID- 16622305
TI  - Cellular localization of NGF and its receptors trkA and p75LNGFR in male
      reproductive organs of the Japanese monkey, Macaca fuscata fuscata.
AB  - The actions of neurotropins are not restricted to the nervous system.
      Immunohistochemical methods were used in the present study to clarify
      distribution of nerve growth factor (NGF) and its receptors TrkA and p75LNGFR in
      excurrent ducts of the adult male Japanese monkey (Macaca fuscata fuscata). NGF
      was found in the seminal vesicle, epididymis, and testis, and has been thought to
      affect male reproductive functions. Leydig cells, Sertoli cells, and
      spermatogonia at various stages were positively stained for NGF, as well as for
      TrkA and p75LNGFR. Signals for these proteins were also found in epithelial cells
      and stromal tissues of the caudal epididymidis, as well as in the seminal
      vesicle. In the prostate, smooth muscle cells and basal cells were positively
      stained for NGF, TrkA, and p75 LNGFR. The results were comparatively discussed.

PMID- 16622307
TI  - Chronic effects of different non-esterified fatty acids on pancreatic islets of
      rats.
AB  - AIMS: The aim of this study was to examine the chronic effects of different non
      esterified fatty acids (NEFA) on insulin secretion by pancreatic islets of normal
      Wistar rats in vitro. METHODS: Pancreatic islets were isolated from normal Wistar
      rats, and were incubated with 0.2, 0.4, or 0.8 mmol/L palmitate (C16:0), stearate
      (C18:0), oleate (C18:1), or linoleate (C18:2) for 24 h, then the insulin
      secretion and pyruvate dehydrogenase (PDH) activity were examined. RESULTS:
      Neither islet insulin content nor islet DNA content differed among islets
      incubated with each kind of NEFA. Compared with control, linoleate significantly
      inhibited glucose-stimulated insulin secretion (GSIS) and PDH activity at each
      concentration (p < 0.05), while others inhibited GSIS and PDH activity
      significantly only at 0.4 and 0.8 mmol/L (p < 0.05). There was no significant
      difference in GSIS and PDH activity among islets pretreated by palmitate,
      stearate, and oleate at the same concentration (p > 0.05). However, linoleate
      decreased GSIS more than others at the same concentration (p < 0.05), while
      linoleate (0.4 or 0.8 mmol/L) inhibited PDH activity more than others at the same
      concentration (p < 0.05). CONCLUSIONS: Elevation of palmitate, stearate, oleate
      or linoleate decreases the beta-cell secretory response to glucose, through
      inhibiting PDH activity. Linoleate exerts more negative effect on GSIS than other
      NEFA.

PMID- 16622306
TI  - COX-1 and -2 expressions in sex-related organs of neonatally estrogen-treated
      rats and in activated and nonactivated macrophage RAW264.7 cells with
      phytoestrogen.
AB  - Cyclooxygenase (COX)-2 is an inducible isoform, expressed in inflamed leukocytes
      and cancer cells. It is known that estrogen causes prostate dysplasia, but little
      is known about COX-2 expression and its influence on male reproductivity. In this
      study, we show that COX-2 was abolished in the distal end of the vas deferens in
      neonatally estrogenized (diethylstilbestrol, NeoDES) Sprague-Dawley (SD) rats at
      age of 15 mo, but the control normal rats were found to remain constitutive
      expression at the same age, while the levels of COX-1 in these rats remained
      intact. Furthermore, BAX, an indicator of sperm quality, was observed in the
      endothelium of vas deferens and sperm of the aged rats. However, COX-2 was not
      detected in the inflamed lesions of NeoDES rat's prostate by
      immunohistochemistry. In addition to estrogen, hydroxymatairesinol (HMR), a
      phytoestrogen, was analyzed in vitro for possible regulation on COX-2. Through
      Western blot analysis, HMR was shown to have no inhibitory affect on COX-2
      expression. These results indicated that estrogen treatment strongly influences
      the expression of COX-2 that is associated with fertility, but no induction of
      COX-2 by estrogen may not exclude COX-2's role in prostatitis, and the anti-tumor
      mechanism of HMR largely remains elusive.

PMID- 16622310
TI  - [State transition of the photosynthetic apparatus in plant].
AB  - State transition of the photosynthetic apparatus in plants is a short-term
      adaptation mediated mainly by the reversible phosphorylation of the main light
      harvesting complex protein (LHCII) and its migration between photosystem I (PSI)
      and photosystem II (PSII). In higher plants and Chlamydomonas, LHCII
      phosphorylation is mainly controlled by the redox state of plastoquinone pool and
      cytochrome b(6)f complex, while salt could induce a redox-independent LHCII
      phosphorylation via transient changes in ion concentrations in Dunaliella. State
      transition can balance the distribution of excitation energy between PSII and PSI
      by changes in light absorption cross section and excitation energy spillover
      between the two photosystems. The preliminary results got in the studies of green
      algae reveal that state transition can also balance the ATP supply and demand.

PMID- 16622308
TI  - Untreated hypopituitarism due to absence of the pituitary stalk with normal adult
      height: report of two cases.
AB  - Patients with congenital multiple pituitary hormones deficiency (MPHD)
      occasionally present with pituitary stalk interruption and ectopic posterior lobe
      on magnetic resonance imaging (MRI). Very rarely normal adult height despite
      growth hormone deficiency (GHD) has been described in these patients. We report
      two patients with evidence of congenital MPHD, who remained untreated until
      adulthood. They both failed to develop spontaneous puberty, and they demonstrated
      very low growth velocity until adulthood when they continued to grow, with a
      final height of 176 and 169 cm when they sought medical attention in our
      department at the age of 45 and 33 yr, respectively. At that time a hypoplastic
      pituitary, absence of pituitary stalk, and ectopic posterior pituitary lobe were
      found on MRI, and the laboratory investigations, including dynamic tests for
      pituitary hormone reserve, revealed MPHD with severe GHD. In conclusion, these
      cases illustrate that very rarely patients with untreated MPHD can reach normal
      adult height. Some postulations about the pathophysiology of this phenomenon are
      discussed.

PMID- 16622311
TI  - [Progress in research on forest tree genomics].
AB  - This is a review on forest tree genomics. In structural genomics, genetic maps
      have been constructed for up to 40 forest tree species, more than 30 commercially
      important QTLs have been detected, comparative mapping has been done for a few of
      forest tree taxa, and whole genome sequencing was completed for Populus and is
      under way for Eucalyptus. For functional genomics, huge EST databases from
      multiple tissues of a number of tree species have been rapidly accumulated, and
      molecular analyses on secondary growth and wood formation, flowering, and cold
      hardiness have given some insights into the metabolic pathways of those tree
      specific development processes. The prospects of development in tree genomics are
      discussed, which may be implicative for accelerating forest tree genomics studies
      in China.

PMID- 16622312
TI  - Physiological responses and tolerance of plant shoot to aluminum toxicity.
AB  - Aluminum (Al) toxicity is one of the most deleterious factors for plant growth in
      acidic soils because over 50% of the world's potentially arable lands are acidic.
      In recent years, considerable research has been conducted to understand the
      mechanisms of Al toxicity and tolerance in plants, and some review papers have
      been published. But most papers addressed mainly the mechanisms of Al toxicity
      and tolerance in plant root system, because inhibition of root growth is one of
      the earliest symptoms of Al injury and the most easily recognized symptom in
      solution culture. This paper reviews the effects of Al on photosynthesis,
      photoprotective systems, water use efficiency (WUE), water content, carbohydrate
      content, mineral nutrition, organic acids, and nitrogen metabolism in plant
      shoot, and also the mechanisms of Al detoxification (chelation of Al with small
      organic compounds, and isolating Al in the some parts, which are insensitive to
      Al, such as vacuoles or epidermal cells) by Al accumulators. Genetics and
      molecular biology of plant Al tolerance, as well as some aspects needed to be
      further studied are also discussed.

PMID- 16622313
TI  - [The relation between en-dormancy and changes in two main electron transport
      pathways of nectarine (Prunus persica var. nectariana) buds].
AB  - Respiration rate of buds of Prunus persica var. nectariana Maxim. cv. Shuguang
      and Mayfire was studied during dormancy. The results showed that the bud
      respiration rate changed with the stage of dormancy for both cultivars.
      Respiration rate of buds of the controls decreased steadily before dormancy,
      while increased slowly from November 5th for Shuguang and October 29th for
      Mayfire, and then decreased sharply on December 17th at which dormancy was
      terminated. Cyanide (KCN) only partially inhibited respiration rate of dormant
      buds of nectarine during the whole period, and the trend of the buds respiration
      rate followed the same pattern as the control samples during the entire period.
      Cyanide inhibited the respiration rate of dormant nectarine buds to roughly the
      same degree. The effect of salicylhydroxamic acid (SHAM) on bud respiration rate
      varied with time. SHAM decreased bud respiration rate before dormancy and after
      the release of dormancy, but increased bud respiration rate during dormancy. SHAM
      increased bud respiration rate more than three times at the beginning of dormancy
      for all buds and the degree decreased gradually along with the dormant period
      until turn to decrease the respiration rate again at the end of dormancy. KCN
      plus SHAM had the same effect on bud respiration rate as SHAM acting alone. The
      time KCN plus SHAM began to increase bud respiration rate or terminated was about
      7 d earlier than SHAM did, which was closely associated with the different stage
      of dormancy.

PMID- 16622314
TI  - [The transformation of betA gene into the pollen plantlets of Populus simonii x
      P. nigra].
AB  - In this study, betA gene was introduced into the pollen plantlets of Populus
      simonii x P. nigra using Agrobacterium-mediated transformation. The four
      kanamycine-resistant plants obtained were identified as transgenic plants by PCR
      detection and the results were all positive. The result of quantitative real-time
      PCR detection showed that the betA gene was transcribed and expressed in all the
      transformed plants, but the transcript levels are different. Test of salt
      tolerance of the transgenic plants showed that 80%-00% of transgenic plants were
      rooted while 0 of non-transgenic plants were rooted at 0.55% NaCl stress, and 0
      of transgenic plants were rooted at 0.70%-0.80% NaCl stress. The betaine content
      analysis showed the betaine content of the transgenic plants are obviously higher
      than that in non-transgenic plants, so transformation betA gene raised the salt
      tolerance to the transgenic plants.

PMID- 16622315
TI  - Steady state fluorescence spectroscopy of the photosystem II core complex.
AB  - Spectroscopic properties within the core complex of photosystem II were
      investigated by studying the influence of the wavelength of excitation on the
      fluorescence emission spectrum. At two temperatures, when the core complex of
      PSII isolated from spinach was excited at six different excitation wavelengths
      ranging from 436 nm to 520 nm, there is no difference in the maxima of the
      emission spectra of the core complex, and when the core complex was excited at
      480, 489, 495 and 507 nm respectively, fluorescence intensities of maxima
      decrease with increasing of the absorbance of the beta-carotene molecules at the
      four excitation wavelengths. The extent of change of the shoulder of the spectra
      beyond 700 nm depends on the kind of pigment molecule excited. The excitation
      wavelength can influence the way of energy transfer in the core complex of
      photosystem II. By Gaussian deconvolution analysis, at least seven groups of
      chlorophyll a molecules were discovered. They are Chl a(660), Chl a(670), Chl
      a(680), Chl a(682), Chl a(684), Chl a(687) and Chl a(690).

PMID- 16622316
TI  - Effects of molybdenum on antioxidative defense system and membrane lipid
      peroxidation in winter wheat under low temperature stress.
AB  - Effects of molybdenum (Mo) on antioxidative defense system and membrane lipid
      peroxidation in leaves of winter wheat (Triticum aestivum H. var. Huamai 8) were
      investigated under low temperature stress. Results of experiments indicate that
      Mo application in winter wheat induced a dramatic decrease in electrolyte leakage
      and malondialdehyde content under low temperature stress. The activities of
      antioxidative enzymes such as superoxide dismutase (SOD, EC 1.15.1.1), peroxidase
      (POX, EC 1.11.1.7) and catalase (CAT, EC 1.11.1.6) were increased by Mo
      application and the extents of increase at low temperature were higher than those
      at normal temperature. Mo application also caused a significant increase in the
      ascorbic acid (AsA) and proline contents both at normal and low temperature and
      following the low temperature stress the increases in ascorbic acid and proline
      contents in Mo-treated winter wheat were higher. There was no significant
      difference in carotenoid (CAR) content between with and without Mo treatment
      under normal temperature, while there was a significant increase in Mo treatment
      under low temperature stress. It could be speculated that Mo application enhanced
      cold resistance by increasing the capacity to scavenge active oxygen species and
      alleviating membrane damage in winter wheat under low temperature stress.

PMID- 16622317
TI  - Glycerate-oxidizing activity of glycolate oxidase from leaves of Spinacia
      oleracea.
AB  - Glycolate oxidase (GO) was purified to homogeneity from leaves of spinach
      (Spinacia oleracea). Through detecting the consumption of oxygen and the
      formation of hydrogen peroxide in the assay solution, it was found that GO could
      also oxidize glycerate, another metabolite in the photorespiratory pathway, and
      use FMN and FAD, but not riboflavin and lumiflavin, as its cofactors. The optimum
      reaction pH, Km for glycerate, k(cat) and activation energy of this oxidizing
      reaction were determined to be 8.0, 7.14 mmol/L, 1.04 s(-1) and 17.29 kJ/mol,
      respectively. Oxalate and pyruvate at 5.0 mmol/L could inhibit the glycerate
      oxidizing activity by 34% and 26%, and oxalate acted as a competitive inhibitor
      of the glycerate oxidation reaction with a K(i) of 0.75 mmol/L. By the
      competition plotting with mixed-substrates, it was indicated that glycolate
      oxidizing activity and glycerate-oxidizing activity of GO shared the same active
      site.

PMID- 16622318
TI  - Effects of Lantana camara leaf extract on the activity of superoxide dismutase
      and accumulation of H2O2 in water hyacinth leaf.
AB  - Water hyacinth (Eichhornia crassipes) is one of the most productive plants, but
      is also a troublesome weed in the world. In order to protect the public water
      system from chemical herbicides pollution, biological method has been suggested
      to control the growth and the reproduction of this weed. Lantana (Lantana camara
      L.) is an important weed of the family Verbenaceae and its leaf extract is highly
      toxic to water hyacinth. The results of this study showed that the extract of
      lantana leaves suppressed the emergence of leaf buds of water hyacinth plant, and
      caused the decay of its leaves by foliar spraying. In addition, the increase of
      SOD activity in water hyacinth leaves was in accordance with the accumulation of
      H(2)O(2) and the increase in degree of membrane peroxidation, while the activity
      of catalase, which might remove the excessive H(2)O(2) in water hyacinth leaves,
      was inhibited by treatment with lantana extract. At tissue level, high H(2)O(2)
      histochemical labeling was detected in guard cells after treatment with lantana
      extract. This overproduction of H(2)O(2) could kill the leaf cells and cause leaf
      necrosis in the treated plant. Therefore, the high toxicity of lantana leaf
      extract to water hyacinth might be due to oxidative stress.

PMID- 16622319
TI  - Identification of betacyanin and effects of environmental factors on its
      accumulation in halophyte Suaeda salsa.
AB  - Effects of temperature, light, salinity and developmental phases on the
      accumulation of red pigments in the C(3) halophyte Suaeda salsa were studied, and
      the physical and chemical characteristics of the red pigments were also analyzed.
      The results indicate that: these red pigments are insoluble in organic solvents
      but free in water, the pigments are red-violet and stable under acidic condition
      while yellow and unstable under alkaline condition, and they absorb the highest
      value at wavelength near 538 nm, light suppresses their accumulation and enhances
      their decomposition. These results suggest that these red pigments are
      betacyanins. Darkness, low temperatures and high salinity enhance betacyanin
      accumulation in Suaeda salsa, and darkness in the germination phase is one of the
      most important environmental factors for the betacyanin accumulation.

PMID- 16622320
TI  - Isolation and expression patterns of LATERAL ORGAN BOUNDARIES-like genes in Lotus
      japonicus.
AB  - A shoot apical meristem (SAM) is composed of several distinct domains and lateral
      organs are initiated at the peripheral zone during plant development.
      Establishment and maintenance of boundary between SAM and lateral organs is an
      important developmental process, in which many regulators are involved. LATERAL
      ORGAN BOUNDARIES (LOB) in Arabidopsis, displaying a specific expression pattern
      corresponding to the boundary of developmental lateral organs, belongs to a large
      gene family--LOB domain gene family, which encode proteins with a conserved LOB
      domain at the N-terminus. Beside LOB, other members of this gene family are also
      involved in divergent developmental processes in Arabidopsis. To investigate the
      functions of LOB-like genes in the distantly related legumes, we isolated LjLOBs
      from a model legume plant Lotus japonicus, and conducted RNA in situ
      hybridization to investigate their expression patterns. It was found that LjLOB1
      and LjLOB3 were strongly expressed at the bases of leaflet primordia, which
      coincided with the boundaries between leaflet primordia and compound leaf
      meristem, while LjLOB4 was expressed at the boundaries between whorls in the
      developing floral bud. The different special expression patterns of LjLOBs
      strongly suggest that their functions in L. japonicus may be divergent: LjLOB1
      and LjLOB3 could play important roles in the control of compound leaf
      development, and LjLOB4 may be required during floral development.

PMID- 16622321
TI  - [Changes in the activities of enzymes involved in starch synthesis and
      accumulation in caryopsis of transgenic rice with antisense Wx gene].
AB  - The amylose content of rice caryopsis is determined by Wx protein, one kind of
      granule-bound starch synthetase which is encoded by Wx gene. Different rice types
      and species have different levels of Wx gene expression and have different
      amylose contents in their caryopsis. Wuyunjing No.7 (2200), the japonica rice
      with an amylose content 17% and its transgenic rice lines with antisense Wx gene
      (2201 and 2203, with amylose contents 8.5% and 2% respectively), and Longtefu
      (LP03), the indica rice with a high amylose content (28%) and its transgenic rice
      with antisense Wx gene (A199, with an amylose content 9%) were used to
      investigate the effects of Wx protein content decrease on the activities of
      enzymes involved in starch synthesis and thereby starch accumulation. The results
      indicated that with the decrease in Wx protein, the amylose content in transgenic
      caryopsis was reduced accordingly, whereas the amylopectin content per caryopsis
      (mg/grain) was not affected, and made the total starch content in transgenic
      caryopsis markedly lower than their parents. With the development of caryopsis,
      the amylose/total starch ratio was not changed significantly in the two parent
      caryopses, LP03 and 2200, but it went down gradually in their transgenic
      caryopses. The amylose/total starch ratio in transgenic caryopses was very
      significantly lower than their parents in the same period. The activities of ADP
      glucose pyrophosphorylase (ADPG-PPase), granule-bound starch synthase (GBSS),
      soluble starch synthase (SSS) and starch branching enzyme (SBE) rose rapidly in
      early periods of grain filling, and soon reached their maximum, then reduced
      quickly until the middle and later periods of grain filling. Compared with the
      parents, the GBSS activity in transgenic caryopsis was significantly lowered, and
      correlated with the amylose reduction. Besides, the maximum activity of GBSS
      appeared earlier, and the range of the activity was smaller. In transgenic
      caryopsis, the activities of ADPG-PPase and SSS were higher than their parents in
      early and middle periods of grain filling, while the SBE activity was higher than
      their parents in middle and late periods.

PMID- 16622322
TI  - [Effects of drought stress on cyanide-resistant respiration and metabolism of
      reactive oxygen in wheat seedling].
AB  - The changes in cyanide-resistant respiration and metabolism of active oxygen
      species in drought-sensitive and drought-resistant wheat seedlings under water
      stress were studied. In general, drought stress decreased the level of cyanide
      resistant respiration and AOX1 mRNA content in wheat seedling leaves. But the
      drought-resistant cultivars, which had much higher level of cyanide-resistant
      respiration and AOX1 mRNA content than the drought-sensitive ones, presented an
      ability to adapt to mild drought stress. Under drought stress, the drought
      sensitive wheat seedling leaves had higher O(-.)(2) and H(2)O(2) contents, but
      lower SOD, POX and CAT activities than drought-resistant cultivars. We guessed
      that severe drought stress could break down the balance between active oxygen
      species and cyanide-resistant respiration. However, cyanide-resistant respiration
      still could participate in the drought-resistance by lowering the level of active
      oxygen species besides by other mechanism.

PMID- 16622323
TI  - [Effects of osmoconditioning on membrane lipid components and fatty acid content
      of cold-sensitive soybean seeds].
AB  - Cold-sensitive soybean (Glycisne max Zhonghuang No.22) seeds were used to
      investigate the effects of osmoconditioning for invigoration of seeds chilling
      tolerance and the changes in membrane lipid by thin layer chromatography and gas
      chromatography to disclose the role of membrane lipid played in imbibitional
      chilling resistance capacity. Results are as follows: being treated with 33%
      PEG6000, seeds germination index, vigor index and root dry weight presented the
      trend of upward as the osmocondition time prolonged. In 72 h, the percentage of
      unsaturated phospholipid (e.g. PC and PE) in soybean seed increased, composition
      of lipid fatty acid changed: the saturated fatty acid 16:0 content in PC, PE, PI
      significantly decreased, while unsaturated fatty acid 18:2 increased greatly,
      which led to increase index of unsaturation fatty acid of lipid. These changes
      were positively corrected with osmoconditioning time. After treated with PEG,
      membrane fluidity increased to provide precondition for preventing imbibitional
      chilling, keeping the integrity of membrane system and normal metabolism.

PMID- 16622324
TI  - [Transferring the Suaeda salsa glutathione S-transferase and catalase genes
      enhances low temperature stress resistance in transgenic rice seedlings].
AB  - The GST (glutathione S-transferase) and GST+CAT1 (catalase 1) of Suaeda salsa
      were introduced into a low temperature-sensitive rice cultivar (Oryza sativa cv.
      Zhonghua No.11) by Agrobacterium tumefaciens-mediated transformation under the
      control of cauliflower mosaic virus (CaMV) 35S promoter, and the transformed
      calli and plantlets were screened on Murashige and Skoog (1962) medium
      supplemented with hygromycin 25 microg/mL and cefotaxime 300 microg/mL. The
      putative primary transformants (T(0) generation) were acclimatized at 26 degrees
      C /22 degrees C in a greenhouse for 7 d, and then transplanted to the field,
      where they grew up to maturity under outdoor conditions. 25 and 14 independent
      transgenic lines of T(1) generation carrying the GST and GST+CAT1 genes,
      respectively, were identified by PCR amplification. Transgene expression was
      monitored by RNA-blot hybridization using total RNA samples from leaf tissues. To
      investigate whether expressing the Suaeda salsa GST and GST+CAT1 in transgenic
      rice increased low temperature stress tolerance, the T(4) 14-day-old transgenic
      and non-transgenic rice seedlings were transferred to a low temperature (day 7
      degrees C/night 4 degrees C) growth chamber for 3-6 d. The experimental data
      showed that expressing the Suaeda salsa GST and GST+CAT1 enhanced low temperature
      stress resistance in transgenic rice seedlings. When treated with low
      temperature, both GST and CAT activity increased in the transformants with the
      time of temperature treatment. These transgenic rice plant seedlings exhibited a
      higher level of photosynthetic capacity than those of the non-transgenic control
      seedlings under low temperature treatment. Whereas, there were lower H(2)O(2) and
      MDA (malondialdehyde) content, and relative electrolyte leakage through the
      plasma membrane was also lower in transgenic rice seedlings than in the parent
      line under low temperature condition. The results also indicated that GST+CAT1 co
      expression conferred greater level of low temperature stress tolerance to the
      transformed rice plants compared to the single GST transformed plants.

PMID- 16622325
TI  - [Effects of sodium nitroprusside on mitochondrial function of rye and wheat root
      tip under aluminum stress].
AB  - Sodium nitroprusside (SNP) could ameliorate the inhibition effect of Al on root
      growth of rye (Secale cereale L. cv. King) and wheat (Triticum aestivum L. cv.
      Jinmai47). Respiratory rate, P/O, OPR (oxygenated phosphate rate), R(3) (oxygen
      consumption rate with ADP and substrate present), R(4) (oxygen consumption rate
      with substrate) and RCR (respiratory control ratio, R(3)/R(4)) of root tips from
      rye and wheat decreased, as well as the activities of H(+)-ATPase, H(+)-PPase,
      Na(+)-K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase, but they increased with SNP
      treatment. It showed that mitochondrial respiratory functions of root tips from
      rye and wheat were damaged, phosphorylation was un-coupled by Al, but that of rye
      was less than that of wheat. Rye has high Al-resistance ability than wheat. SNP
      is one of donor of NO, it is suggested that NO can ameliorate remarkably
      respiratory dysfunction resulted from Al stress, so that NO can ameliorate the
      inhibition effect of Al on plant growth.

PMID- 16622326
TI  - [Changes in water state and soluble protein contents of wampee axes during
      inducing desiccation tolerance by sucrose preculture].
AB  - Progressively increasing sucrose concentration of culture medium could increase
      desiccation tolerance of wampee [Clausena lansium (Lour.) Skeels] axes. The
      changes in water state and soluble proteins of axes during acquirement of
      desiccation tolerance were measured by differential scanning calorimeter (DSC)
      and SDS-PAGE. The results showed that the cooling and heating thermograms of
      sucrose-precultured axes were similar to those of the control; but there was a
      stepwise change in the heating thermograms of sucrose-precultured axes, implying
      that vitrification might occur in axes. Unfreezable water amounts of wampee axes
      were measured, the results showed that amounts of unfreezable water of sucrose
      precultured axes and control were 25.4% and 25.9% (by the linear regression
      equation method), or 24.3% and 23.7% (by the heat of ice fusion method)
      respectively, which were not significantly different. The soluble protein content
      of sucrose-precultured axes was 68% higher than the control, and SDS-PAGE showed
      that a 20-kD protein markedly increased in content.

PMID- 16622327
TI  - [A two-dimensional electrophoresis protocol suitable for proteomic study of rice
      leaves].
AB  - A 2-DE (two-dimensional electrophoresis) protocol suited for the separation of
      proteins from rice leaves was established. Protein extraction, quantitative
      loading of samples and concentrations of the gel were modified and improved to
      minimize markedly the interference by leaf pigments and other non-protein
      substances, thus resulting in satisfactory separation results.

PMID- 16622328
TI  - [Effects of exogenous nitric oxide, salicylic acid and hydrogen peroxide on free
      amino acid and soluble protein contents in tobacco leaves].
AB  - The work focused on the effects of signal molecules of nitric oxide (NO),
      salicylic acid (SA) and hydrogen peroxide (H(2)O(2)) on compounds of nitric
      metabolites of free amino acid, soluble protein and proline in tobacco. The
      results indicated that NO, SA and H(2)O(2) were able to regulate the proline,
      free amino acid and soluble protein content in tobacco. Lower concentration of NO
      and H(2)O(2) raised the level of proline; while higher concentration of NO and
      H(2)O(2) lowered the proline, free amino acid content in tobacco. The above three
      signal molecules also showed similar effects on proline, free amino acid and
      soluble protein content in tobacco.

PMID- 16622329
TI  - Resolution of SPECT-determined anterior cerebral hypoperfusion correlated with
      maintenance ECT-derived improvement in residual symptoms in a case of late-life
      psychotic depression.
AB  - A 70-year-old widow with recurrent psychotic depression was successfully treated
      with maintenance electroconvulsive therapy (ECT) for 4 years up to the present.
      Anterior cerebral hypoperfusion visualized by single photon emission computerized
      tomography (SPECT) before ECT persisted (second SPECT study 14 days after the
      last ECT session) despite a response to the first course of acute ECT. Only mild
      symptoms remained. Relapse occurred 2 weeks after the post-ECT SPECT study. The
      hypoperfusion improved after response to a second course of acute ECT (per SPECT
      5 days after the last ECT session), and perfusion was normalized after 2-year
      maintenance ECT (per SPECT 14 days after the last ECT session). The normalization
      coincided with improvement in depressive symptoms remaining after the second
      course of acute ECT. We speculate that the effectiveness of maintenance ECT might
      have been in part the result of the improvement in residual symptoms and that
      resolution of the persistent anterior hypoperfusion, which might underlie medical
      refractoriness, illness chronicity, and relapse tendency in late-life depression,
      might have been associated with the improvement in residual symptoms achieved by
      maintenance ECT.

PMID- 16622330
TI  - Treatment of neuroblastoma using the fused imaging guided radiotherapy (FIGURA)
      system.
AB  - PURPOSE: The purpose of this study was to describe our department's experience
      with the fused imaging-guided radiotherapy (FIGURA) system for planning radiation
      treatment of high-risk neuroblastoma. PATIENTS AND METHODS: Between 1999 and
      2002, 11 patients received radiation therapy as consolidation after chemotherapy
      in 9 and for palliation in 2. Diagnostic metaiodobenzylguanidine (MIBG) imaging
      was used, which is specific for neuroblastoma, to identify the residual tumor,
      followed by computed tomography scanning in the radiation treatment position. The
      FIGURA software fused the images obtained by the 2 modalities and transferred the
      result to a 3-dimensional radiation treatment planning system. Radiation was
      delivered at a total dose of 25.2 Gy according to the FIGURA. RESULTS: Five
      patients achieved complete remission and 2 partial remission; 3 were stabilized.
      One child with a highly rapid progressive course died of the disease. CONCLUSION:
      FIGURA is a new, feasible technique for defining target volumes. By using
      standard hospital equipment, it is possible to treat residual disease identified
      by sensitive metaiodobenzylguanidine imaging and localized with the anatomic
      computed tomography scan. Treating a more accurate target volume spares normal
      tissue and organs and minimizes side effects.

PMID- 16622331
TI  - F-18 FDG PET demonstrates crossed cerebellar diaschisis 20 years after stroke.
AB  - Stroke produces an area of focal damage and distant areas of reduced blood blow
      and metabolism termed diaschisis. Tc-99m ECD and HMPAO brain SPECT have
      demonstrated crossed cerebellar diaschisis (CCD) in patients with cerebral
      cortical infarct. SPECT findings reflect abnormal cerebral blood flow. CCD as
      shown on F-18 FDG PET reflects abnormal reflects glucose metabolism. We present
      the case of a patient with laryngeal cancer who also had a stroke in the left
      cerebral hemisphere involving the territory of the middle cerebral artery 20
      years ago. This patient underwent PET, including the head and neck. A current
      brain F-18 FDG PET exhibited hypometabolism in the contralateral cerebellum (CCD)
      as well as hypometabolism of the primary insult in the left cerebral hemisphere.
      These findings reflect partial impairment or diminished glucose metabolism in the
      primary insult to the cerebrum and contralateral cerebellum. In addition, this
      patient illustrates that on PET imaging, CCD could be demonstrated 20 years after
      a stroke.

PMID- 16622332
TI  - Relationship between gastric emptying and gastroesophageal reflux in infants and
      children.
AB  - PURPOSE: The aim of our study was to evaluate the relationship between gastric
      emptying and gastroesophageal reflux (GER) in infants and children. METHODS AND
      MATERIALS: One hundred eight patients (pts) between 3 months and 5 years of age
      (77 boys, 31 girls) with clinical suspicion of GER disease were included in the
      study. Patients were divided into 2 groups according to the age range: group A, 0
      2 years (57 pts), and group B, 2-5 (51 pts) years. Each group was divided into 2
      subgroups according to the scintigraphic study as GER-positive and -negative.
      Cow's milk with Tc-99m sulfur colloid as radiotracer was used. Gastric emptying
      was expressed as the half emptying time (T1/2). The detection of activity in the
      esophagus at any time during scintigraphy was considered an indicator of GER
      episodes. Reflux episodes were graded as grade 1 if activity was detected on one
      or 2 frames and grade 2 if activity was detected on more than 2 frames. RESULTS:
      Forty of the 108 patients (37%) had GER findings on scintigraphy. The comparison
      of gastric emptying time between positive GER scintigraphy and negative GER
      scintigraphy groups was not statistically significant in any age group. No
      association was found between age and rate of gastric emptying time. Although the
      comparison of T1/2 between grade 1 patients and the GER-negative group was not
      statistically significant, grade 2 patients showed significant differences and
      had prolonged gastric emptying times. Mild statistical correlation between the
      number of reflux episodes and gastric emptying half time was found. CONCLUSIONS:
      As a conclusion, the relation between gastroesophageal reflux and delayed gastric
      emptying cannot be ignored. Our results support delayed gastric emptying to be a
      pathogenetic factor in gastroesophageal reflux in infants and children.

PMID- 16622333
TI  - PET-CT demonstration of extensive muscle metastases from breast cancer.

PMID- 16622334
TI  - Solitary fibular metastasis from lung cancer mimicking stress fracture.

PMID- 16622335
TI  - Methotrexate-induced pulmonary non-Hodgkin lymphoma.

PMID- 16622336
TI  - The value of F-18 FDG triple-head coincidence PET in the posttreatment evaluation
      of patients with lymphoma.

PMID- 16622337
TI  - F-18 FDG PET evaluation of bronchial plasmacytoma with CT and MRI correlation.

PMID- 16622338
TI  - Leiomyosarcoma of the inferior vena cava.

PMID- 16622339
TI  - V-Q SPECT in prone position is a suitable way to improve irradiation of
      inoperable lung cancer.

PMID- 16622340
TI  - Ventilation/perfusion mismatch in septic pulmonary emboli from pacemaker
      infection.

PMID- 16622341
TI  - Significantly elongated sagging gallbladder can mimic intestine in hepatobiliary
      scintigraphy and cause false-positive interpretation for acute cholecystitis.

PMID- 16622342
TI  - Unexpected finding of umbilical hernia during peritoneal scintigraphy.

PMID- 16622343
TI  - Gastric and splenic visualization in hepatic artery perfusion scintigraphy (HAPS)
      secondary to aberrant vascular flow.

PMID- 16622344
TI  - Renovascular hypertension and double renal arterial supply diagnosed by Tc-99m
      MAG3 captopril renography.

PMID- 16622345
TI  - Calyceal diverticulum mimicking a renal tumor on FDG PET imaging.

PMID- 16622346
TI  - Usefulness of imaging in disseminated tuberculosis.

PMID- 16622347
TI  - Tc-99m ECD SPECT and FDG PET in partial status epilepticus resulting from
      cerebral sparganosis.

PMID- 16622348
TI  - Current readings in nuclear medicine.

PMID- 16622356
TI  - A mathematical theory for identifying and measuring severity of episodes of care.
AB  - OBJECTIVES: We propose and test a method for constructing episodes of care from
      data within administrative databases and electronic health records. SUBJECTS: We
      created a measure for severity of episodes of illness for 565 randomly chosen
      developmentally delayed children who were enrolled in the Medicaid program.
      DESIGN: Regression analysis was conducted to test the percentage of variance
      explained by our proposed mathematical model in cost of care. DATA COLLECTION:
      Data included both hospitalizations and clinic visits obtained from Medicaid
      programs from one southeastern state. METHODS: For each patient, the likelihood
      that two diagnoses are part of the same episode is proportional to the similarity
      of the two diagnoses and to the short time interval between them. When this
      likelihood exceeds a preset cutoff, then the two diagnoses are part of the same
      episode. The cutoff is estimated by selecting number of days before two very
      similar diagnoses are considered to be part of separate episodes. The similarity
      between two diagnoses is assumed to be proportional to co-occurrence of the two
      diagnoses within a fixed period (usually 30 days). The severity of an episode was
      calculated using a Muliplicative Multiattribute Utility model, where severity of
      each diagnosis is aggregated to estimate the overall severity of the episode.
      Severity of each diagnosis was assumed to be proportional to average cost of a
      diagnosis-if patients do not die before care is delivered. The article includes
      an algorithm that can classify a patient's diagnosis into episodes of care and
      measure severity of the episodes from date of diagnoses, code for the diagnoses,
      and charges for the visit. To facilitate integration with existing database, the
      article includes a Standard Query Language computer program. To evaluate the
      method of constructing episodes of care, we regressed cost of care on the
      patient's number of episodes of care within the year, average severity of the
      episodes within the year, and the interaction between number and average severity
      of the episodes. RESULTS: The number of episodes (alpha = .001), the average
      severity of the episodes (alpha = .001), and the product of the two (alpha =
      .001) had statistically significant relationships to the average cost of the
      case. The 3 variables together explained 53% of variation in yearly cost of care.
      CONCLUSIONS: These data suggest that our proposed mathematical approach is
      reasonable and produces severity scores that are predictive of objective criteria
      such as cost of care.

PMID- 16622357
TI  - Readmission data for outcomes measurement: identifying and strengthening the
      empirical base.
AB  - Hospital readmission is an important indicator of patient care outcomes and is
      widely used in evaluating the quality of health care provided. However, few
      definitions of the term "readmission" are listed in the literature, and exact
      measurement parameters regarding readmission are seldom stated. The term
      readmission is indiscriminately used and defined, making accurate comparisons of
      results difficult across studies if not impossible. This article analyzes the
      concept readmission, creates a criteria-based definition for the term, and
      proposes a measurement instrument on the basis of these criteria to consistently
      quantify readmission in quality management programs and research studies.
      Multiple databases were searched using various key terms to locate literature
      covering adult and pediatric populations and all clinical conditions or
      diagnoses. Articles were selected on the basis of the specified
      inclusion/exclusion criteria.

PMID- 16622358
TI  - Physician gender and primary care patient satisfaction: no evidence of
      "feminization".
AB  - BACKGROUND: Observers predict that the influx of women into the medical
      profession will alter the way in which medicine is practiced, incorporating more
      "feminine" values of caring, listening to patients, and patient centeredness, in
      contrast to the "masculine" values of curing, dictating to patients, and care
      provider centeredness. Consequently, patient satisfaction with medical care will
      improve. SUBJECTS AND METHODS: Retrospective database analysis of satisfaction
      survey data. A total of 3985 surveys from primary care patients were examined
      after having identified the gender of the patient's physician. Ten survey items
      that pertained to physician attributes were analyzed, individually and in the
      aggregate, in a series of 2 x 2 analyses of covariance, with physician gender and
      patient gender serving as independent variables, and patient age and the overall
      level of patient satisfaction from the physician's facility serving as
      covariates. An additional analysis of covariance, with the same independent
      variables and covariates, examined patients expressed likelihood of recommending
      their physician to others. RESULTS AND CONCLUSIONS: There were no main or
      interaction effects for physician gender or patient gender after adjusting for
      patient age and facility-level satisfaction. The implications of these results
      for the "feminization" hypothesis are discussed.

PMID- 16622359
TI  - Reverse quality management: developing evidence-based best practices in health
      emergency management.
AB  - The British Columbia Ministry of Health's Framework for Core Functions in Public
      Health was the catalyst that inspired this review of best practices in health
      emergency management. The fieldwork was conducted in the fall of 2005 between
      hurricane Katrina and the South Asia earthquake. These tragedies, shown on 24/7
      television news channels, provided an eyewitness account of disaster management,
      or lack of it, in our global village world. It is not enough to just have best
      practices in place. There has to be a governance structure that can be held
      accountable. This review of best practices lists actions in support of an
      emergency preparedness culture at the management, executive, and
      corporate/governance levels of the organization. The methodology adopted a future
      quality management approach of the emergency management process to identify the
      corresponding performance indictors that correlated with practices or sets of
      practices. Identifying best practice performance indictors needed to conduct a
      future quality management audit is described as reverse quality management. Best
      practices cannot be assessed as stand-alone criteria; they are influenced by
      organizational culture. The defining of best practices was influenced by doubt
      about defining a practice it is hoped will never be performed, medical staff
      involvement, leadership, and an appreciation of the resources required and how
      they need to be managed. Best practice benchmarks are seen as being related more
      to "measures" of performance defined locally and agreed on by 2 or more parties
      rather than to achieving industrial standards. Relating practices to performance
      indicators and then to benchmarks resulted in the development of a Health
      Emergency Management Best Practices Matrix that lists specific practice in the
      different phases of emergency management.

PMID- 16622360
TI  - Why we love quality but hate to measure it.
AB  - As a group, physicians strive for quality but often resist quality measurement.
      Cost, inconvenience, lack of time, mistrust of quality measures, and a fear of
      what assessment may find are all factors contributing to this resistance.
      However, quality, in both rich and poor counties, continues to be poor at worse
      and varied at best. If we are to improve the quality of our care, we need quality
      measurement to show us our weaknesses. A variety of tools are available to assess
      quality, which, when followed by the right policy interventions, can lead to
      improved care. Quality measurements are most effective when they are comparative,
      reflect the complexity of clinical practice, are not expected to be a panacea for
      spiraling costs, and are made available to our colleagues and our patients.

PMID- 16622361
TI  - Interview with Janis Anfossi, JD.

PMID- 16622364
TI  - Hydroxyapatite dip coated and uncoated titanium poly-axial pedicle screws: an in
      vivo bovine model.
AB  - STUDY DESIGN: A 1-year-old calf was implanted with titanium pedicle screws either
      uncoated (n = 7) or coated with hydroxyapatite (n = 7) by the dipping method on
      the pedicles of vertebrae (t10-l3). OBJECTIVE: To evaluate biomechanical and
      histomorphologic responses to titanium pedicle screws uncoated and coated with
      hydroxyapatite. SUMMARY OF BACKGROUND DATA: Failure of fixation caused by
      loosening of pedicle screws is a problem in spinal surgery. Enhancement of the
      fixation ability of screws by coating with biocompatible materials may improve
      prognosis of surgery. METHODS: The calf was euthanized 4 months after
      implantation for determination of insertion and extraction torques for screws,
      and histologic and scanning electron microscopic examinations of areas screw
      embedded. RESULTS: Insertion torques did not differ by the kind of screws (99 +/-
      5.7 Ncm). However, extraction torques for screws coated with hydroxyapatite were
      higher than for screws uncoated (249 vs. 133 Ncm, P < 0.01). As compared with
      uncoated screws, implanted areas for hydroxyapatite-coated screws were denser,
      had more cracks, and provided better bonding. Fibrous tissue and new bone
      formation were observed around the areas of uncoated and hydroxyapatite-coated
      screws embedded, respectively. CONCLUSIONS: Hydroxyapatite coating of titanium
      pedicle screws by the dipping method improved fixation and vertebral bone-implant
      interface, suggesting a decreased risk of a screw-loosening problem.

PMID- 16622365
TI  - Computerized tomographic measurement of the cervical pedicles diameter in a
      Malaysian population and the feasibility for transpedicular fixation.
AB  - STUDY DESIGN: The cervical pedicle diameter size differs between Asians and non
      Asians. The authors studied the transverse pedicle diameter of the C2-C7 of the
      cervical spine in a Malaysian population using computerized tomography (CT)
      measurements. The transverse diameter of the pedicle is the determinant of the
      feasibility of this technique because the sagittal diameter of the pedicle has
      been wider than the transverse pedicle diameter. OBJECTIVES: To study the average
      transverse pedicle diameter of the cervical spine in a Malaysian population, and
      evaluate the feasibility and safety of pedicle screw fixation in these patients.
      SUMMARY OF BACKGROUND DATA: Cervical transpedicular screw fixation has been safe
      and is most probably going to be the gold standard for cervical spine fixation.
      However, its use in the Asian population should be considered cautiously because
      our cervical pedicle diameter may not be adequate to accommodate the standard
      pedicle screw size, which can be dangerous because there are vital structures
      located adjacent to the pedicles. METHODS: The measurements of the cervical
      pedicles were performed on CT images using its measurement tools. CT cutting was
      made at 2.5-mm intervals. The pedicle transverse diameters were defined as the
      most outer diameter of the pedicle, taken perpendicular to the axis of the
      pedicle and measured in millimeters up to 0.1 mm. RESULTS: The mean transverse
      diameters of the cervical pedicle of C2, C3, C4, C5, C6, and C7 in males were
      5.4, 5.2, 5.1, 5.2, 5.5, and 6.5 mm, respectively, and ranged between 5.1 and 6.5
      mm. In females, the mean transverse diameter of the cervical pedicle of C2, C3,
      C4, C5, C6, and C7 were 5.0, 4.6, 4.7, 4.9, 5.2, and 5.6 mm, respectively, and
      ranged between 4.6 and 5.6 mm. If the minimum transverse diameter required is 5.0
      mm for 3.5-mm screw insertion, about 4.2% to 54.2% (male) of pedicles at
      different levels and 6.7% to 73.3% (females) of patients cannot have fixation
      with a 3.5-mm screw using this technique. CONCLUSION: Transpedicular screw
      fixation for the cervical spine must not be attempted in the Malaysian population
      before the exact pedicle diameters are known.Therefore, preoperative CT
      evaluation is a must before transpedicular fixation is performed, especially in
      female patients. Because the margin for mistake is very narrow, it is best
      avoided in upper cervical spines.

PMID- 16622366
TI  - Diffuse idiopathic skeletal hyperostosis associated with risk factors for stroke:
      a case-control study.
AB  - STUDY DESIGN: The incidence of risk factors for cerebrovascular diseases was
      investigated in patients with diffuse idiopathic skeletal hyperostosis (DISH) and
      patients with cervical spondylosis. OBJECTIVES: To investigate the association
      between DISH and cerebrovascular disease. SUMMARY OF BACKGROUND DATA: DISH is a
      common skeletal disease mainly affecting the anterior and lateral spinal
      longitudinal ligaments. The principal clinical features are nonradicular pain,
      stiffness, dysphagia (cervical portion), and associated ossification of the
      posterior longitudinal ligament. METHODS: Age- and sex-matched patients were
      divided into three groups: 45 patients with DISH, 45 patients with cervical
      spondylosis Grade I and II, and 45 patients with cervical spondylosis Grade III
      and IV. Anthropometric, laboratory, and magnetic resonance (MR) imaging findings
      were analyzed. RESULTS: The values of uric acid (P = 1.60 x 10) and alkaline
      phosphatase (P = 2.00 x 10) were significantly greater in patients with DISH than
      in the other groups. Patients with DISH had a significantly higher incidence of
      ossification of the posterior longitudinal ligament (P = 5.21 x 10). Stiffness
      was significantly more common in patients with DISH and patients with spondylosis
      Grade III and IV than in patients with spondylosis Grade I and II (P = 0.000232).
      The incidence of infarction on MR imaging was significantly higher in patients
      with DISH than in the other groups (P = 0.0120). The incidence of stenosis or
      occlusion of a major cerebral artery on MR angiography was significantly higher
      in patients with DISH than in the other groups (P = 0.00264). CONCLUSIONS: DISH
      is associated with increased incidences of risk factors for stroke and
      cerebrovascular disease.

PMID- 16622368
TI  - Mesenchymal chondrosarcoma treated with total en bloc spondylectomy for 2
      consecutive lumbar vertebrae resulted in continuous disease-free survival for
      more than 5 years: case report.
AB  - STUDY DESIGN: A case report of an extremely rare malignant spinal tumor
      successfully treated with total en bloc spondylectomy and chemotherapy.
      OBJECTIVE: To describe points for consideration when an osteogenic lesion in the
      spine is diagnosed and treated. SUMMARY OF BACKGROUND DATA: Primary mesenchymal
      chondrosarcoma in the spine is extremely rare. There were no reports of this
      tumor being treated with spondylectomy to achieve total surgical resection with a
      wide margin followed by chemotherapy. METHODS: A 44-year-old female presented
      with low back pain and left flank pain. Magnetic resonance imaging and
      computerized tomography showed an osteosclerotic tumor of the lumbar vertebrae.
      Tc-99m HMDP bone scintigraphy was positive, but thallium-201 scintigraphy and
      gallium scintigraphy were negative. The patient was diagnosed as having
      chondrosarcoma based on biopsy findings. RESULTS: To resect the tumor completely,
      total en bloc spondylectomy for 2 consecutive lumbar vertebrae was performed.
      However, the postoperative pathologic diagnosis was extremely difficult because
      the patient was initially suspected to have osteosarcoma, but the final diagnosis
      was mesenchymal chondrosarcoma. Five years after surgery, there have not been any
      signs of local recurrence or distant metastasis, and the patient has remained
      continuously disease free. CONCLUSIONS: To our knowledge, we reported the first
      case of mesenchymal chondrosarcoma occurring from the lumbar spine treated with
      total en bloc spondylectomy and chemotherapy. Successful radical resection of the
      tumor could be accomplished. Although the effect of chemotherapy on the final
      results could not be clearly determined, considering that at least continuous
      disease-free survival was achieved, it is highly likely that chemotherapy
      contributed to the favorable results.

PMID- 16622369
TI  - Cervical degenerative cyst located within the body of C2: a case report and
      review of the literature.
AB  - STUDY DESIGN: A case report and review of the literature are presented.
      OBJECTIVES: To describe the clinical course and treatment of a patient with an
      unusual intraosseous degenerative cyst within the body of the axis, as well as
      review the literature regarding these lesions. SUMMARY OF BACKGROUND DATA:
      Intraosseous degenerative cysts of the cervical spine are extremely rare. To our
      knowledge, only 4 prior case studies have described these lesions, 2 of which
      were seen in the body of C2. METHODS: A case report of a 58-year-old patient with
      neck pain and an intraosseous cyst within the axis is presented with a review of
      the pertinent literature. RESULTS: History, examination, radiographic evaluation,
      and histology revealed this lesion to be an intraosseous degenerative cyst within
      the body of C2. The patient was treated with anterior surgical biopsy/curettage
      and posterior stabilization with structural graft enhancement. CONCLUSION:
      Although rare, intraosseous cervical degenerative cysts should be present in any
      differential diagnosis of cystic lesions seen in the cervical spine.

PMID- 16622371
TI  - A 5-year follow-up evaluation of the health and economic consequences of an early
      cognitive behavioral intervention for back pain: a randomized, controlled trial.
AB  - STUDY DESIGN: A 5-year follow-up of a randomized, controlled trial. OBJECTIVE: To
      evaluate the long-term health and economic consequences of a cognitive behavioral
      intervention. SUMMARY OF BACKGROUND DATA: Linton and Andersson (Spine
      2000;25:2825-31) provide 1 of only a few studies on the preventive effects of a
      cognitive behavioral intervention. The present study is a 5-year follow-up.
      METHODS: In the original study, 213 participants were randomized to the cognitive
      behavioral group intervention or to usual care plus information on self-care
      (information comparison group). Of participants, 97% completed a follow-up
      questionnaire 5 years after the intervention, and supplemental records were
      obtained from the National Insurance Authority. RESULTS: The cognitive behavioral
      group had significantly less pain, was more active, enjoyed better quality of
      life, and had better general health relative to the information comparison group.
      There was no difference on health care use. The risk of long-term sick leave was
      3 times higher in the information comparison group. The cognitive behavioral
      group had significantly less lost productivity costs and a lower total
      cost/y/person (16,514 Swedish kronor) compared to the information comparison
      group (45,990 Swedish kronor). CONCLUSIONS: A cognitive-behavioral group
      intervention produces long-term health and economic benefits. Usual medical care
      might be improved considerably by implementing these psychologic methods.

PMID- 16622372
TI  - Combined anterior plus posterior stabilization versus posterior short-segment
      instrumentation and fusion for mid-lumbar (L2-L4) burst fractures.
AB  - STUDY DESIGN: Prospective randomized study. OBJECTIVES.: To compare the results
      of the combined anterior-posterior surgery (Group A) with posterior "short
      segment" transpedicular fixation (SSTF) (Group B) in mid-lumbar burst fractures.
      SUMMARY OF BACKGROUND DATA: There are no comparative randomized clinical studies
      on the outcome following operative treatment of mid-lumbar fractures. METHODS:
      Forty consecutive patients with L2-L4 fresh single A3-type/AO burst fractures and
      load sharing score up to 6 were randomly selected to underwent either combined
      one-stage anterior stabilization with mesh cage and SSTF (Group A) or solely SSTF
      with intermediate screws in the fractured vertebra (Group B). Kyphotic Gardner
      angle, anterior and posterior vertebral body height (PVBHr, AVBHr), spinal canal
      encroachment (SCE), SF-36, VAS, and Frankel classification were used. RESULTS:
      The follow-up observation averaged 46 and 48 months for Group A and B,
      respectively. Operative time, blood loss, and hospital stay were significant more
      in Group A. More surgical complications were observed in the Group A. After
      surgery, VAS was reduced to 4.3 and 3.6 for Group A and Group B, respectively.
      The SF-36 domains Role physical and Bodily pain improved significantly only in
      Group B (P = 0.05) and (P = 0.06), respectively. Correction of AVBHr, PVBHr, and
      spinal canal clearance was similar in both groups. Spinal canal clearance did not
      differ between the two groups, but it was continuous until the last evaluation in
      Group B. The final Gardner angle loss of correction averaged 2 degrees and 5
      degrees for Group A and Group B, respectively. The posttraumatic Gardner
      deformity did not significantly improve by SSTF at the final evaluation in the
      spines of Group B. Gardner angle correlated significantly with SCE in Group B and
      Group A in all three periods and in the last evaluation, respectively. Frankel
      grade did not correlate with loss of correction of AVBHr and PVBHr in Group A,
      while it significantly correlated with loss of PVBHr correction and SCE in the
      patients of Group B. There was no neurologic deterioration after surgery in any
      patient. VAS and SF-36 scores did not significantly correlate with the loss of
      kyphotic angle correction and AVBHr, PVBHr at the final observation in any
      patient of both groups. CONCLUSIONS: SSTF offered similar significant short-term
      correction of posttraumatic deformities associated with mid-lumbar A3-burst
      fractures, but better clinical results as compared to combined surgery. However,
      SSTF did not significantly maintain the after surgery achieved correction of
      local posttraumatic kyphosis at the final evaluation. Thus, SSTF is not
      recommended for operative stabilization of fractures with this severity.

PMID- 16622373
TI  - Effects on improvement of blood flow in the chronically compressed cauda equina:
      comparison between a selective prostaglandin E receptor (EP4) agonist and a
      prostaglandin E1 derivate.
AB  - STUDY DESIGN: Vasodilatation was studied in a model of experimental chronic cauda
      equina compression using measurements of vessel diameter on video recordings.
      OBJECTIVE: The vasodilative effect was compared between a prostaglandin E2
      receptor (EP) subtype agonists (EP4 agonist) and a prostaglandin E1 (PGE1)
      derivate. SUMMARY AND BACKGROUND DATA: Reduction of blood flow is one important
      pathogenic factor of neurogenic intermittent claudication (NIC) for lumbar spinal
      canal stenosis. It is known that PGE1 improves the mean walking distance in
      patients with cauda equina compression type of NIC. There are four subtypes of
      EP: EP1, EP2, EP3, and EP4. EP4 is located in vessels of pigs and rabbits. A
      highly selective EP4 agonist, which has effects on dilatation of pig and rabbit
      vessels, has recently been developed. One may therefore assume that this agonist
      may improve blood flow in the chronically compressed cauda equina. METHODS: A
      total of 25 dogs were used. A plastic balloon inflated to 10 mm Hg was placed
      under the lamina of the seventh lumbar vertebra for 1 week. OP-1206 cyclodextrin
      clathrate (OP-1206 CD: prostaglandin E1 derivate) and ONO-4819 CD (a highly
      selective EP4 agonist) were intravenously administrated. The following 5
      experimental groups were assigned: animals in group OP (3) (n = 5) and Group OP
      (10) (n = 5) received 3 eta g/kg per minute and 10 eta g/kg per minute of OP-1206
      CD, respectively; those in Group EP (3) (n = 5) and Group EP (10) (n = 5)
      received 3 eta g/kg per minute and 10 eta g/kg per minute of ONO-4819 CD,
      respectively; and those in the control group (n = 5) received saline. After 7
      days, the cauda equina was exposed and blood vessels of the second or third
      sacral nerve root were identified using a specially designed operation microscope
      equipped with a video camera. The diameters of the observed blood vessels were
      measured on video-recordings every 10 minutes until 60 minutes after
      administrating OP-1206 CD or ONO-4819CD. RESULTS: In the Groups OP (3), OP (10),
      and EP (10), the blood vessels were dilated and blood flow increased after
      injection of the agents. In the Group EP (10), the vessel diameter and blood flow
      increased significantly compared with that in the other four groups. In contrast,
      the blood vessels contracted and the blood flow was reduced in the Group EP (3).
      CONCLUSIONS: Our results suggested that the EP4 agonist at high concentrations
      might be a potential therapeutic agent since it is expected to increase blood
      flow in nerve roots in patients with spinal canal stenosis.

PMID- 16622374
TI  - Notochordal cell produce and assemble extracellular matrix in a distinct manner,
      which may be responsible for the maintenance of healthy nucleus pulposus.
AB  - STUDY DESIGN: Analysis of proteoglycan synthesis, distribution and assembly of
      notochordal cells and small nucleus pulposus cells embedded in alginate beads and
      cultured in presence of [S]-Na2SO4. OBJECTIVE: To determine whether the
      degeneration of the nucleus pulposus of the intervertebral disc is associated
      with a change in the cell phenotype. SUMMARY OF BACKGROUND DATA: The loss of the
      notochordal cell from the nucleus pulposus is associated with ageing and disc
      degeneration. The reduction in their numbers after birth in humans and in the
      chondrodystrophoid dog has been suggested to result from cell death and
      replacement or differentiation by chondrocytes. The almost total disappearance of
      the notochordal cells in the nucleus pulposus correlates with early degenerative
      changes in the disc and a concomitant reduction in proteoglycan content,
      increased collagen, and loss of water content. The basic mechanism of this
      accelerated degeneration with ageing is poorly understood. METHODS: Nucleus
      pulposus and anulus fibrosus cells were isolated from the lumbar intervertebral
      discs of chondrodystrophoid and nonchondrodystrophoid dogs. The cells from the
      nucleus pulposus were further separated by size into notochordal cells and small
      nucleus pulposus cells. Cells were embedded in alginate beads and cultured in the
      presence of [S]-Na2SO4 to measure proteoglycan size, rate of synthesis, and
      distribution into the pericellular and intercellular compartments. RESULTS: Large
      notochordal cells in the nucleus pulposus of chondrodystrophoid dogs formed 13%
      of the cell population in young dogs and fell to 0.4% in adults, whereas they
      were the predominant cell type in the nonchondrodystrophoid dogs at all ages.
      These cells were capable of 1.5-fold greater rate of synthesis of proteoglycans
      than the small nucleus pulpous cells. Proteoglycans secreted by the large cells
      were evenly distributed between the pericellular and intercellular
      compartments,whereas the small cells distributed 3-fold more proteoglycan into
      the intercellular phase. By size exclusion chromatography, the proteoglycans
      synthesized by the small cells of the chondrodystrophoid dogs formed large-size
      aggregates (Kav = 0.1) within the pericellular region, which then moved to the
      intercellular region over 5 to 10 days. In contrast, proteoglycans secreted by
      the notochordal cells were capable of rapid migration to the intercellular phase
      before assembly into large-sized aggregates. The ability to form aggregates was
      independent of age of the animal. CONCLUSIONS: Our model shows that a change in
      intervertebral disc cell phenotype correlates with the grade of disc degeneration
      and that the notochordal cells synthesize proteoglycans, which exhibit delayed
      aggregation than those synthesized by the small nucleus pulposus cells. This
      implies that the cell type composition of the nucleus pulposus of the
      chondrodystrophoid and nonchondrodystrophoid dogs produces an extracellular
      matrix that is assembled in a distinct manner, which may affect tissue integrity.

PMID- 16622376
TI  - Toward an optimum system for intervertebral disc organ culture: TGF-beta 3
      enhances nucleus pulposus and anulus fibrosus survival and function through
      modulation of TGF-beta-R expression and ERK signaling.
AB  - STUDY DESIGN: Rat lumbar discs comprising nucleus pulposus, annulus fibrosus, and
      cartilaginous endplates were cultured for 1 week in a specialized media
      containing either TGF-beta1 or TGF-beta3. Role of TGF-beta isoforms on cell
      function was evaluated. OBJECTIVE: To develop an in vitro organ culture of rat
      intervertebral disc and evaluate effects of TGF-beta3 on disc cell function.
      SUMMARY OF BACKGROUND DATA: An in vitro model system is of considerable value in
      understanding the cell biology of the intervertebral disc. Development of a
      useful organ culture model would enhance understanding of disc function in health
      and disease. MATERIALS AND METHODS: Rat lumbar intervertebral discs were
      maintained in organ culture in media supplemented with TGF-beta3 or TGF-beta1 for
      1 week. Tissue morphology was studied using routine histologic, histochemical and
      immunohistochemical techniques. Cell function was assessed by gene expression,
      sulfate incorporation, and Western blot analysis. RESULTS: After 1 week in
      culture with TGF-beta3 and TGF-beta1, the gross morphology and tissue
      architecture of the disc were preserved. TUNEL analysis indicated that there was
      no evidence of cell death in the nucleus pulposus or the anulus fibrosus. The
      level of Alcian blue staining in the nucleus pulposus was similar to that of the
      freshly isolated disc. However, when compared with TGF-beta1, TGF-beta3 elevated
      the expression of critical matrix genes, enhanced [S] incorporation into
      proteoglycans, preserved the expression of TGF-beta receptors, and decreased
      aggrecan turnover. There was also increased activation (phosphorylation) of ERK,
      a critical signaling protein. Moreover, inhibition of ERK activity, in the
      presence TGF-beta3, resulted in suppression of collagen Type II, aggrecan, TGF
      beta-RI, TGF-beta-RII and TGF-beta-RIII mRNA expression. CONCLUSIONS: TGF-beta3
      maintains the phenotype of disc cells in organ culture. It exerts this effect, in
      part, by elevating the levels of activated ERK1/2, which in turn regulates the
      expression of TGF-beta-RI and TGF-beta-RII.

PMID- 16622377
TI  - Paraspinal muscle vasculature contributes to posterolateral spinal fusion.
AB  - STUDY DESIGN: Study of posterolateral fusions in a rabbit model. OBJECTIVES: To
      characterize the contribution of paraspinal musculature to the healing of
      posterolateral spinal fusions in a rabbit model. SUMMARY OF BACKGROUND DATA:
      Previous studies have demonstrated that successful spinal arthrodesis requires
      vascular ingrowth from adjacent decorticated bone. In other areas of the body,
      such as the tibia, vascular ingrowth from the surrounding musculature has also
      been shown to be important. The role of the surrounding paraspinal musculature in
      spinal fusions has yet to be assessed. METHODS: Twenty-five New Zealand white
      rabbits underwent posterolateral spinal fusion. One side of the animals was
      treated with autograft alone and served as the control group. On the
      contralateral side, the autograft was contained within porous or nonporous
      barrier sheets. Following euthanization, high-resolution radiographs, CT scans,
      and histologic analyses were performed to assess fusion and characterize vascular
      ingrowth. RESULTS: Using histologic evaluation, the fusion rate in the porous
      group was 90%, in the nonporous group 40%, and in the control group 55%. Vascular
      ingrowth was evident from the muscle through the porous sheet into the fusion
      mass. CONCLUSIONS: These results support our hypothesis that the paraspinal
      musculature provides important vascular ingrowth into the fusion site. Use of a
      porous barrier sheet appears to improve fusion by preventing muscle interposition
      while allowing vascular ingrowth from surrounding muscle.

PMID- 16622378
TI  - Three-level anterior cervical discectomy and fusion with plate fixation:
      radiographic and clinical results.
AB  - STUDY DESIGN: Retrospective review of patients with cervical spondylosis treated
      with 3-level anterior cervical discectomy and fusion with plate fixation.
      OBJECTIVE: To assess the radiographic and clinical outcome of 3-level
      instrumented anterior cervical discectomy. SUMMARY OF BACKGROUND DATA: Three
      level cervical discectomy without plate fixation has shown high rates of
      pseudarthrosis and poor outcomes. The addition of internal fixation may improve
      these parameters. METHODS: A total of 46 patients were observed for an average of
      17.6 months (range, 6-51 months). All had 3-level anterior cervical discectomy
      and fusion with tricortical iliac crest autograft (4 cases), fibular ring
      allograft (38 cases), or titanium cage (4 cases). Allografts and cages were
      filled with iliac crest autograft. All patients had semirigid plating. Clinical
      and radiographic follow-up data were obtained. Clinical outcomes were measured as
      described by Robinson and with the Nurick scale. RESULTS: Forty-four patients
      achieved solid fusion. Two patients had additional surgery for junctional
      disease, and in 1 of them pseudarthrosis repair was also performed. One
      asymptomatic pseudarthrosis was noted. With a successful result defined as an
      excellent or good outcome accompanied by significant pain relief, 38 patients had
      a successful result (83%). Radiographic adjacent level disease was diagnosed in
      11 patients after surgery and was symptomatic in 5. CONCLUSION: Three-level
      anterior cervical discectomy with plate fixation has a high rate of fusion, a low
      complication rate, and acceptable outcome in the treatment of multilevel cervical
      spondylosis.

PMID- 16622379
TI  - Neck injury mechanisms during direct face impact.
AB  - STUDY DESIGN: Digitized measurements of the intervertebral motions using cervical
      cineradiographs of 10 volunteers during direct impacts applied to their faces.
      OBJECTIVES: To clarify the cervical spine motion during direct face impact and
      postulate some mechanisms of neck injuries. SUMMARY OF BACKGROUND DATA: Neck
      injury occurs mostly in traffic or falling accidents. Hyperextension of the neck
      is considered the most common mechanism of the injury because most victims have
      lacerations or contusions on their faces. METHODS: A low-level backward impact
      load was applied to 10 healthy male volunteers' faces at the forehead and maxilla
      via a strap using a free-falling small mass. Cervical vertebral motion was
      recorded by radiograph cineradiography during the impact. RESULTS: The upper
      cervical spine showed a flexion motion for both conditions. Consequently, the
      cervical spine had an S-shaped curvature similar to that in cervical retraction.
      Intervertebral motions of the cervical spine were evaluated using an radiograph
      frame taken at the maximum cervical retraction. For the forehead load,
      intervertebral motion at C1-C2 was flexion, and motions of the lower cervical
      spine were extension. For the maxilla load, intervertebral motions from occiput
      C1 through C4-C5 were flexion. The inflection point of the curvature was
      influenced by the impact location. CONCLUSION: We detected a flexion motion of
      the upper or middle cervical spine during direct face impact. In an actual
      accident, if the cervical spine is forced into similar motion, we speculate that
      neck injury would occur in this retraction-like curvature of the cervical spine.

PMID- 16622380
TI  - Low back pain in pediatric athletes with unilateral tracer uptake at the pars
      interarticularis on single photon emission computed tomography.
AB  - STUDY DESIGN: Retrospective clinical study with radiographic and medical chart
      review. OBJECTIVE: To study the clinical characteristics and outcome of pediatric
      athletes with low back pain and unilateral tracer uptake on single photon
      emission computed tomography (SPECT) at the pars interarticularis but no defect
      on radiographs. SUMMARY OF BACKGROUND DATA: Some pediatric athletes with low back
      pain have no findings on plain radiographs but a unilateral SPECT uptake at the
      pars interarticularis. However, little is known about these patients. METHODS:
      Twenty-two pediatric athletes who had low back pain with increased tracer uptake
      on SPECT unilaterally at the pars interarticularis but no defect on plain
      radiograph were evaluated. The following criteria were used for evaluation: age,
      male-to-female ratio, duration of symptoms, vertebral level, and presence of
      spina bifida occulta or scoliosis. RESULTS: The average age was 12.3 +/- 2.5
      years. The male-to-female ratio was 1.2:1. The average duration of symptoms was
      21 +/- 23 weeks. Nineteen (86%) had increased uptake at L5. Six (27%) had spina
      bifida occulta and 8 (36%) had scoliosis. Eighteen (82%) patients showed an
      excellent outcome. The patients who presented with a longer history of symptoms
      or a concomitant spina bifida occulta had an increased risk of having occasional
      aching with vigorous activity when compared with the patients who did not (P <
      0.05). CONCLUSIONS: Athletes who have low back pain and increased tracer uptake
      unilaterally at the pars interarticularis on SPECT are younger than those
      previously reported patients with spondylolysis proven by a defect on
      radiographs. Some of these lesions do progress to "frank" spondylolysis seen on
      radiographs, but favorable clinical outcomes from nonoperative treatment can be
      expected. Patients with a longer pain history or concomitant spina bifida occulta
      may need careful follow-up because they are at increased risk of having
      occasional low back pain.

PMID- 16622381
TI  - Cement leakage in percutaneous vertebroplasty: effect of preinjection gelfoam
      embolization.
AB  - STUDY DESIGN: Prospective case series. OBJECTIVES: To determine the safety and
      feasibility of routine preinjection of gelfoam embolization during percutaneous
      vertebroplasty. SUMMARY OF BACKGROUND DATA: Percutaneous vertebroplasty has been
      used effectively in pain relief for vertebral fractures resulting from malignancy
      and osteoporosis. However, cement extrusion is a common problem and can lead to
      complications. Gelfoam embolization of venous channels before cement injection
      has not been widely used as a technique to prevent leakage. METHODS: Thirty-one
      patients who met the inclusion-exclusion criteria for the study underwent
      percutaneous vertebroplasty. Venography was first performed to determine the flow
      pattern in the vertebrae and confirm needle placement. Next, routine gelfoam
      embolization of venous channels was performed. This was followed by low-pressure,
      minimal-volume cement injection. The outcome measure of cement leakage was
      assessed after surgery using radiographs and CT scans. RESULTS: There were no
      complications. In the 31 patients, 61 levels of vertebroplasty were performed.
      Overall, there were 16 leaks out of 61 levels in 12 patients (26.2%). In
      osteoporotic fractures, there were 11 leaks in 49 levels, giving a leakage rate
      of 22.5%. There was only 1 epidural leak in this group (2%), and this was
      asymptomatic. Seven leakages were into the adjacent disc, 2 into the body, and 1
      into the paravertebral tissues. In malignant fractures, there were 5 leakages out
      of 12 levels (41.7%). Of these, 2 were epidural leaks (16.7%), which were
      asymptomatic. CONCLUSIONS: Complications resulting from leakage are the most
      feared side effect of the procedure. This has resulted in only limited
      application of vertebroplasty in the United Kingdom. Routine gelfoam embolization
      together with careful technique has been shown to be a safe and feasible method
      during vertebroplasty.

PMID- 16622382
TI  - The diagnostic effect of various needle tip positions in selective lumbar nerve
      blocks: an analysis of 1202 injections.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVE: To determine the effect of
      various needle tip positions on immediate postinjection pain in selective lumbar
      nerve blocks. SUMMARY OF BACKGROUND DATA: To our knowledge, no large study has
      examined the effect of various needle tip positions within or adjacent to the
      intervertebral foramen on immediate pain outcome. METHODS: A total of 1774 cases
      of intervertebral lumbar nerve blocks performed by our radiology staff between
      April 7, 1997 and May 31, 2002, were reviewed. Of the 1774 cases, 1202 met the
      study criteria (i.e., a single-level injection in an adult). The position of the
      needle tip and degree of immediate postinjection pain relief were examined.
      RESULTS: The blocks resulted in an average pain reduction of 4.14 U, as graded on
      a 0-10 ordinate scale (95% confidence interval 3.98-4.30). The degree of pain
      reduction was not associated with the needle tip position. CONCLUSIONS: Our
      results suggest that precise needle tip position within or adjacent to the
      intervertebral foramen made no difference on immediate pain reduction. These
      findings allow the practitioner more freedom in performing an injection. This
      study does not evaluate the long-term effects of various needle tip positions in
      selective lumbar nerve blocks.

PMID- 16622383
TI  - Three-dimensional classification of spinal deformities using fuzzy clustering.
AB  - STUDY DESIGN: A prospective study of a large set of three-dimensional (3D)
      reconstructions of spinal deformities in adolescent idiopathic scoliosis (AIS).
      OBJECTIVES: To determine the value of fuzzy clustering techniques to
      automatically detect clinically relevant 3D curve patterns within this set of 3D
      spine models. SUMMARY OF BACKGROUND DATA: Classification is important for the
      assessment of AIS and has been mainly used to guide surgical treatment. Current
      classification systems are based on visual curve pattern identification using two
      dimensional radiologic measurements but remain controversial because of their low
      interobserver and intraobserver reliability. A clinically useful 3D
      classification remains to be found. METHODS: An unsupervised learning algorithm,
      fuzzy k-means clustering, was applied on 409 3D spine models. Analysis of data
      distribution using clinical parameters was performed by studying similar curve
      patterns, near each cluster center identified. RESULTS: The algorithm determined
      that the entire sample of models could be segmented in five easily differentiated
      curve patterns similar to those of the Lenke and King classifications.
      Furthermore, a system with 12 classes made possible the identification of
      subpatterns of spinal deformity with true 3D components. CONCLUSIONS: Automatic
      and clinically relevant 3D classification of AIS is possible using an
      unsupervised learning algorithm. This approach can now be used to build a
      relevant 3D classification of AIS using appropriate key features of 3D models
      selected by a panel of expert spinal deformity surgeons.

PMID- 16622384
TI  - Discrepancy between disability and the severity of low back pain: demographic,
      psychologic, and employment-related factors.
AB  - STUDY DESIGN: Survey of a random sample of all registered residents of Japan
      between the ages of 20 and 79 years (n = 2966), focusing on those who had had low
      back pain (LBP) within the past month (n = 906). OBJECTIVE: To learn more about
      the characteristics of people in whom the severity of LBP and the disability
      attributed to that pain are discrepant. SUMMARY OF BACKGROUND DATA: LBP can cause
      disability, but levels of pain and of disability can be discrepant. Some people
      with severe pain are only slightly disabled, some with mild pain are very
      disabled, and others have no such discrepancy. METHODS.: Severity of LBP was
      measured with a visual analog scale. Disability was measured with the Roland
      Morris Disability Questionnaire, which quantifies disability in many daily
      activities, not necessarily disability related to employment. The respondents
      also provided demographic information, and completed the SF-36 and questionnaires
      about perceived stress, employment, and satisfaction with employment. RESULTS: In
      about 45% of those patients with LBP, the severity of the pain and level of
      disability attributed to that pain were discrepant. People with a high level of
      disability despite only mild pain were older, felt more stress, were more
      depressed, worked more overtime, and were less satisfied with their job content,
      income, working conditions, and relationships with coworkers. People with little
      disability despite severe pain were the opposite in all those respects.
      CONCLUSIONS: A group of patients with LBP can be identified for whom the most
      appropriate interventions should consider psychosocial factors.

PMID- 16622386
TI  - Nonsurgical resource utilization in adult spinal deformity.
AB  - STUDY DESIGN: The enrollment data were retrospectively reviewed for 1,061
      patients entered into a prospective multicenter study of adult spinal deformity
      between January 2002 and June 2004. OBJECTIVE: The purpose of this study is to
      quantify and analyze the use of nonsurgical resources in patients with adult
      spinal deformity. SUMMARY OF BACKGROUND DATA: Limited data exist regarding the
      utilization of nonsurgical treatment methods for adult spinal deformity. METHODS:
      Demographic data, surgical history, symptom assessment, and nonsurgical treatment
      regimen were reviewed. Health status measures were the SF-12, SRS-29, and ODI.
      Nonsurgical patients were divided into low- and high-symptom subgroups based on
      age adjusted ODI score. Resource utilization was analyzed based on both patient
      and physician questionnaire responses. RESULTS: High- and low-symptom nonsurgical
      subgroups differed significantly on all reported health status measures (P <
      0.0001). High-symptom patients used greater resources in terms of narcotics,
      epidural blocks, and physical agent methods (P < 0.001), analgesics (P < 0.01),
      pain management referral and bed rest (P < 0.02), strength training, nerve root
      blocks, and stabilization exercises (P < 0.05). CONCLUSIONS: The results of this
      study demonstrate that, within the population of adult deformity patients,
      distinct high- and low-symptom groups exist and can be clearly identified. While
      high-symptom patients used significantly greater resources, most low-symptom
      patients used nonsurgical resources as well.

PMID- 16622387
TI  - Computed tomography assessment of the accuracy of in vivo placement of artificial
      discs in the lumbar spine including radiographic and clinical consequences.
AB  - STUDY DESIGN: Prospective cohort study of 52 patients who had undergone
      artificial lumbar disc replacement. OBJECTIVES: To evaluate the implantation
      accuracy of prosthesis positioning, subsequent facet joint changes and prosthesis
      migration, and the clinical consequences of implant position. SUMMARY OF
      BACKGROUND DATA: Accuracy of spinal prosthesis implantation has not been
      evaluated rigorously, especially with a mini-incision approach. It is unknown if
      the inexact placement of a mobile device in the spine has any biomechanical,
      radiographic, or clinical repercussions. METHODS: A total of 52 consecutive
      patients were treated using standard methods of disc implantation with an
      intervertebral prosthesis. Computed tomography scans were performed within 3 days
      and again at 6 to 24 months. An independent radiologist analyzed the images for
      prosthesis position, rotation, migration, and facet changes. Results were
      compared with clinical outcome, measured by the Visual Analog Scale and Oswestry
      Disability Index. RESULTS: Deviation of the prosthesis from the center position
      was under 1.2 mm, and rotation off of midline was under 12 degrees. Follow-up CT
      scans showed no migration or facet changes. Regression analysis showed no
      correlation of prosthesis position with clinical outcome. CONCLUSIONS: Current
      prosthetic disc implantation methods, with minimally invasive access techniques,
      are relatively accurate. Although there can be deviation of the prosthesis from
      ideal placement, no repercussions were attributable.

PMID- 16622388
TI  - Tranexamic acid for hemostasis in the surgical treatment of metastatic tumors of
      the spine.
AB  - STUDY DESIGN: This is a retrospective study of sequential cohorts. OBJECTIVE: To
      assess the efficacy of tranexamic acid in decreasing operative blood loss and the
      need for intraoperative transfusion in metastatic spine surgery. SUMMARY OF
      BACKGROUND DATA: Significant published data have established the efficacy of
      antifibrinolytic drugs in limiting surgical bleeding during heart surgery and
      total joint replacement. One study in scoliosis suggested benefit in spine
      surgery as well. METHODS: During a 6-month trial period, 14 patients with spine
      cancer undergoing palliative intralesional tumor excision and concomitant
      instrumentation to stabilize the spine in the hands of a single surgeon were
      administered tranexamic acid intraoperatively in the attempt to minimize
      operative blood loss. They were then compared to the immediately preceding 14
      patients. RESULTS: Estimated operative blood loss was 1385 mL in the study group
      treated with tranexamic acid and 1815 mL in controls not receiving the drug, and
      was not found to be significantly decreased in this study. CONCLUSIONS: Control
      of operative bleeding in metastatic spine surgery can be problematical. Optimum
      protocol might include routine preoperative angiographic tumor embolization to
      decrease lesion vascularity in all cases, but angiography is not without risk.
      Noninvasive prophylaxis of tumor bleeding would have obvious desirable advantages
      but was, unfortunately, not achieved in this study.

PMID- 16622390
TI  - Corneal graft dehiscence during pneumatic retinopexy.

PMID- 16622391
TI  - Subretinal abscess and endogenous endophthalmitis caused by beta-lactamase
      positive Moraxella species.

PMID- 16622392
TI  - Bilateral macular holes in usher syndrome.

PMID- 16622393
TI  - A new technique for the subretinal injection of small volumes by using a modified
      viscous fluid injector system.

PMID- 16622394
TI  - Preventive treatment of migraine.
AB  - Migraine preventive therapy, even in the absence of a headache, is given in an
      attempt to reduce the frequency, duration, or severity of attacks. Circumstances
      that might warrant preventive treatment include disabling migraine attacks, the
      overuse of acute medications or failure of or contraindication to acute
      medications, troublesome side effects from medication, hemiplegic migraine, or
      very frequent headaches (more than 2 a week). The major medication groups for
      preventive treatment include anticonvulsants, antidepressants, b-adrenergic
      blockers, calcium channel antagonists, serotonin antagonists, neurotoxins,
      nonsteroidal anti-inflammatory drugs, and others. If preventive medication is
      indicated, the agent preferentially should be chosen from one of the first-line
      categories, based on the drug's side-effect profile and the patient's coexistent
      and comorbid conditions.

PMID- 16622395
TI  - Parasitic central nervous system infections: echinococcus and schistosoma.
AB  - Central nervous system (CNS) manifestations of Echinococcus and Schistosoma
      infections occur throughout the world, with incidence increasing in developed
      regions. A detailed literature review generated a current summary on
      epidemiology, parasitology, pathology, clinical manifestations, imaging studies,
      diagnosis, and treatment of neuroechinococcosis and neuroschistosomiasis. Recent
      advancements have been made in diagnosis, treatment, and prevention of these
      parasitic CNS infections. Ongoing advancements in neuroimaging and diagnostic
      studies, as well as efforts to better understand the parasite genome and host
      parasite relationships, will likely continue to improve patient management.

PMID- 16622396
TI  - Practical strategies for switching to newer antiepileptic drugs.
AB  - Traditional antiepileptic drugs (AEDs) are associated with drug interactions and
      side effects that limit their safety and tolerability. Side effects of
      traditional AEDs are especially problematic for children and adolescents, women
      of childbearing age, and the elderly. Many patients with epilepsy may benefit
      from switching from a traditional AED to a newer agent because the newer agents
      are generally better tolerated and are less likely to cause drug interactions.
      Clinical studies have demonstrated improved therapeutic efficiency with better
      tolerability in patients switching from a traditional AED to lamotrigine,
      oxcarbazepine, or topiramate monotherapy or combination therapy.

PMID- 16622397
TI  - Giant cell arteritis, thoracic outlet syndrome, and idiopathic intracranial
      hypotension. Highlights from the 57th annual meeting of the American Academy of
      Neurology, April 9-16, 2005, Miami Beach, FL.

PMID- 16622398
TI  - Update on idiopathic narcolepsy and the symptomatic narcolepsies. Summary of
      presentations given at the teaching course at the 19th annual meeting of the
      Associated Professional Sleep Societies, June 18-23, 2005, Denver, CO.

PMID- 16622399
TI  - Women and stroke. Highlights from Advancing the Study of Stroke in Women, August
      22-23, 2005, Durham, NC.

PMID- 16622400
TI  - Drug overdose in a young man: a not-so-happy face.
AB  - Patients who are found comatose and remain in this state are a diagnostic
      challenge for neurologists and emergency room (ER) physicians. In this case, a
      drug addict, who was found comatose, had to be intubated when he arrived in the
      ER. Diagnostic strategies focus on using neuroimaging to establish the cause,
      especially when characteristic abnormalities appear. Therapeutic options also are
      discussed.

PMID- 16622404
TI  - Two-step activation of ATM by DNA and the Mre11-Rad50-Nbs1 complex.
AB  - DNA double-strand breaks (DSBs) trigger activation of the ATM protein kinase,
      which coordinates cell-cycle arrest, DNA repair and apoptosis. We propose that
      ATM activation by DSBs occurs in two steps. First, dimeric ATM is recruited to
      damaged DNA and dissociates into monomers. The Mre11-Rad50-Nbs1 complex (MRN)
      facilitates this process by tethering DNA, thereby increasing the local
      concentration of damaged DNA. Notably, increasing the concentration of damaged
      DNA bypasses the requirement for MRN, and ATM monomers generated in the absence
      of MRN are not phosphorylated on Ser1981. Second, the ATM-binding domain of Nbs1
      is required and sufficient to convert unphosphorylated ATM monomers into
      enzymatically active monomers in the absence of DNA. This model clarifies the
      mechanism of ATM activation in normal cells and explains the phenotype of cells
      from patients with ataxia telangiectasia-like disorder and Nijmegen breakage
      syndrome.

PMID- 16622405
TI  - WRN exonuclease structure and molecular mechanism imply an editing role in DNA
      end processing.
AB  - WRN is unique among the five human RecQ DNA helicases in having a functional
      exonuclease domain (WRN-exo) and being defective in the premature aging and
      cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal
      structures, biochemical activity and participation in DNA end joining. Metal-ion
      complex structures, active site mutations and activity assays reveal a nuclease
      mechanism mediated by two metal ions. The DNA end-binding Ku70/80 complex
      specifically stimulates WRN-exo activity, and structure-based mutational
      inactivation of WRN-exo alters DNA end joining in human cells. We furthermore
      establish structural and biochemical similarities of WRN-exo to DnaQ-family
      replicative proofreading exonucleases, describing WRN-specific adaptations
      consistent with double-stranded DNA specificity and functionally important
      conformational changes. These results indicate WRN-exo is a human DnaQ family
      member and support DnaQ-like proofreading activities stimulated by Ku70/80, with
      implications for WRN functions in age-related pathologies and maintenance of
      genomic integrity.

PMID- 16622406
TI  - Structural plasticity of single chromatin fibers revealed by torsional
      manipulation.
AB  - Magnetic tweezers were used to study the mechanical response under torsion of
      single nucleosome arrays reconstituted on tandem repeats of 5S positioning
      sequences. Regular arrays are extremely resilient and can reversibly accommodate
      a large amount of supercoiling without much change in length. This behavior is
      quantitatively described by a molecular model of the chromatin three-dimensional
      architecture. In this model, we assume the existence of a dynamic equilibrium
      between three conformations of the nucleosome, corresponding to different
      crossing statuses of the entry/exit DNAs (positive, null or negative,
      respectively). Torsional strain displaces that equilibrium, leading to an
      extensive reorganization of the fiber's architecture. The model explains a number
      of long-standing topological questions regarding DNA in chromatin and may provide
      the basis to better understand the dynamic binding of chromatin-associated
      proteins.Note: In the supplementary information initially published online to
      accompany this article, Supplementary Figure 2 was mistakenly replaced by
      Supplementary Equation 2. The error has been corrected online.

PMID- 16622407
TI  - APOBEC3G DNA deaminase acts processively 3' --> 5' on single-stranded DNA.
AB  - Akin to a 'Trojan horse,' APOBEC3G DNA deaminase is encapsulated by the HIV
      virion. APOBEC3G facilitates restriction of HIV-1 infection in T cells by
      deaminating cytosines in nascent minus-strand complementary DNA. Here, we
      investigate the biochemical basis for C --> U targeting. We observe that APOBEC3G
      binds randomly to single-stranded DNA, then jumps and slides processively to
      deaminate target motifs. When confronting partially double-stranded DNA, to which
      APOBEC3G cannot bind, sliding is lost but jumping is retained. APOBEC3G shows
      catalytic orientational specificity such that deamination occurs predominantly 3'
      --> 5' without requiring hydrolysis of a nucleotide cofactor. Our data suggest
      that the G --> A mutational gradient generated in viral genomic DNA in vivo could
      result from an intrinsic processive directional attack by APOBEC3G on single
      stranded cDNA.

PMID- 16622408
TI  - Reconstruction of the chemotaxis receptor-kinase assembly.
AB  - In bacterial chemotaxis, an assembly of transmembrane receptors, the CheA
      histidine kinase and the adaptor protein CheW processes environmental stimuli to
      regulate motility. The structure of a Thermotoga maritima receptor cytoplasmic
      domain defines CheA interaction regions and metal ion-coordinating charge centers
      that undergo chemical modification to tune receptor response. Dimeric CheA-CheW,
      defined by crystallography and pulsed ESR, positions two CheWs to form a cleft
      that is lined with residues important for receptor interactions and sized to
      clamp one receptor dimer. CheW residues involved in kinase activation map to
      interfaces that orient the CheW clamps. CheA regulatory domains associate in
      crystals through conserved hydrophobic surfaces. Such CheA self-contacts align
      the CheW receptor clamps for binding receptor tips. Linking layers of ternary
      complexes with close-packed receptors generates a lattice with reasonable
      component ratios, cooperative interactions among receptors and accessible sites
      for modification enzymes.

PMID- 16622409
TI  - Carbohydrate recognition by Clostridium difficile toxin A.
AB  - Clostridium difficile TcdA is a large toxin that binds carbohydrates on
      intestinal epithelial cells. A 2-A resolution cocrystal structure reveals two
      molecules of alpha-Gal-(1,3)-beta-Gal-(1,4)-beta-GlcNAcO(CH(2))(8)CO(2)CH(3)
      binding in an extended conformation to TcdA. Residues forming key contacts with
      the trisaccharides are conserved in all seven putative binding sites in TcdA,
      suggesting a mode of multivalent binding that may be exploited for the rational
      design of novel therapeutics.

PMID- 16622410
TI  - EJC-independent degradation of nonsense immunoglobulin-mu mRNA depends on 3' UTR
      length.
AB  - Inconsistent with prevailing models for nonsense-mediated mRNA decay (NMD) in
      mammals, the mRNA levels of immunoglobulin-mu (Ig-mu) genes with premature
      termination codons (PTCs) in the penultimate exon are still reduced by NMD when
      the intron furthest downstream is deleted. As in yeast, this exon junction
      complex-independent NMD of Ig-mu mRNAs depends on the distance between the
      termination codon and the poly(A) tail and suggests an evolutionarily conserved
      mode of PTC recognition.

PMID- 16622413
TI  - The principles of guiding by RNA: chimeric RNA-protein enzymes.
AB  - The non-protein-coding transcriptional output of the cell is far greater than
      previously thought. Although the functions, if any, of the vast majority of these
      RNA transcripts remain elusive, out of those for which functions have already
      been established, most act as RNA guides for protein enzymes. Common features of
      these RNAs provide clues about the evolutionary constraints that led to the
      development of RNA-guided proteins and the specific biological environments in
      which target specificity and diversity are most crucial to the cell.

PMID- 16622416
TI  - APPL1 binds to adiponectin receptors and mediates adiponectin signalling and
      function.
AB  - Adiponectin, also known as Acrp30, is an adipose tissue-derived hormone with anti
      atherogenic, anti-diabetic and insulin sensitizing properties. Two seven
      transmembrane domain-containing proteins, AdipoR1 and AdipoR2, have recently been
      identified as adiponectin receptors, yet signalling events downstream of these
      receptors remain poorly defined. By using the cytoplasmic domain of AdipoR1 as
      bait, we screened a yeast two-hybrid cDNA library derived from human fetal brain.
      This screening led to the identification of a phosphotyrosine binding domain and
      a pleckstrin homology domain-containing adaptor protein, APPL1 (adaptor protein
      containing pleckstrin homology domain, phosphotyrosine binding (PTB) domain and
      leucine zipper motif). APPL1 interacts with adiponectin receptors in mammalian
      cells and the interaction is stimulated by adiponectin. Overexpression of APPL1
      increases, and suppression of APPL1 level reduces, adiponectin signalling and
      adiponectin-mediated downstream events (such as lipid oxidation, glucose uptake
      and the membrane translocation of glucose transport 4 (GLUT4)). Adiponectin
      stimulates the interaction between APPL1 and Rab5 (a small GTPase) interaction,
      leading to increased GLUT4 membrane translocation. APPL1 also acts as a critical
      regulator of the crosstalk between adiponectin signalling and insulin signalling
      pathways. These results demonstrate a key function for APPL1 in adiponectin
      signalling and provide a molecular mechanism for the insulin sensitizing function
      of adiponectin.

PMID- 16622417
TI  - The phox homology domain of phospholipase D activates dynamin GTPase activity and
      accelerates EGFR endocytosis.
AB  - Dynamin is a large GTP-binding protein that mediates endocytosis by hydrolyzing
      GTP. Previously, we reported that phospholipase D2 (PLD2) interacts with dynamin
      in a GTP-dependent manner. This implies that PLD may regulate the GTPase cycle of
      dynamin. Here, we show that PLD functions as a GTPase activating protein (GAP)
      through its phox homology domain (PX), which directly activates the GTPase domain
      of dynamin, and that the arginine residues in the PLD-PX are vital for this GAP
      function. Moreover, wild-type PLD-PX, but not mutated PLD-PXs defective for GAP
      function in vitro, increased epidermal growth factor receptor (EGFR) endocytosis
      at physiological EGF concentrations. In addition, the silencing of PLDs was shown
      to retard EGFR endocytosis and the addition of wild-type PLDs or lipase-inactive
      PLDs, but not PLD1 mutants with defective GAP activity for dynamin in vitro,
      resulted in the recovery of EGFR endocytosis. These findings suggest that PLD,
      functioning as an intermolecular GAP for dynamin, accelerates EGFR endocytosis.
      Moreover, we determined that the phox homology domain itself had GAP activity - a
      novel function in addition to its role as a binding motif for proteins or lipids.

PMID- 16622418
TI  - Synaptopodin orchestrates actin organization and cell motility via regulation of
      RhoA signalling.
AB  - The Rho family of small GTPases (RhoA, Rac1 and Cdc42) controls signal
      transduction pathways that influence many aspects of cell behaviour, including
      cytoskeletal dynamics. At the leading edge, Rac1 and Cdc42 promote cell motility
      through the formation of lamellipodia and filopodia, respectively. On the
      contrary, RhoA promotes the formation of contractile actin-myosin-containing
      stress fibres in the cell body and at the rear. Here, we identify synaptopodin,
      an actin-associated protein, as a novel regulator of RhoA signalling and cell
      migration in kidney podocytes. We show that synaptopodin induces stress fibres by
      competitive blocking of Smurf1-mediated ubiquitination of RhoA, thereby
      preventing the targeting of RhoA for proteasomal degradation. Gene silencing of
      synaptopodin in kidney podocytes causes the loss of stress fibres and the
      formation of aberrant non-polarized filopodia and impairment of cell migration.
      Together, these data show that synaptopodin is essential for the integrity of the
      podocyte actin cytoskeleton and for the regulation of podocyte cell migration.

PMID- 16622419
TI  - The human CENP-A centromeric nucleosome-associated complex.
AB  - The basic element for chromosome inheritance, the centromere, is epigenetically
      determined in mammals. The prime candidate for specifying centromere identity is
      the array of nucleosomes assembled with CENP-A, the centromere-specific histone
      H3 variant. Here, we show that CENP-A nucleosomes directly recruit a proximal
      CENP-A nucleosome associated complex (NAC) comprised of three new human
      centromere proteins (CENP-M, CENP-N and CENP-T), along with CENP-U(50), CENP-C
      and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M,
      CENP-N and CENP-T. Facilitates chromatin transcription (FACT) and nucleophosmin-1
      (previously implicated in transcriptional chromatin remodelling and as a
      multifunctional nuclear chaperone, respectively) are absent from histone H3
      containing nucleosomes, but are stably recruited to CENP-A nucleosomes
      independent of CENP-A NAC. Seven new CENP-A-nucleosome distal (CAD) centromere
      components (CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S) are
      identified as assembling on the CENP-A NAC. The CENP-A NAC is essential, as
      disruption of the complex causes errors of chromosome alignment and segregation
      that preclude cell survival despite continued centromere-derived mitotic
      checkpoint signalling.

PMID- 16622420
TI  - The CENP-H-I complex is required for the efficient incorporation of newly
      synthesized CENP-A into centromeres.
AB  - In vertebrates, centromeres lack defined sequences and are thought to be
      propagated by epigenetic mechanisms involving the incorporation of specialized
      nucleosomes containing the histone H3 variant centromere protein (CENP)-A.
      However, the precise mechanisms that target CENP-A to centromeres remain poorly
      understood. Here, we isolated a multi-subunit complex, which includes the
      established inner kinetochore components CENP-H and CENP-I, and nine other
      proteins, from both human and chicken cells. Our analysis of these proteins
      demonstrates that the CENP-H-I complex can be divided into three functional sub
      complexes, each of which is required for faithful chromosome segregation.
      Interestingly, newly expressed CENP-A is not efficiently incorporated into
      centromeres in knockout mutants of a subclass of CENP-H-I complex proteins,
      indicating that the CENP-H-I complex may function, in part, as a marker directing
      CENP-A deposition to centromeres.

PMID- 16622421
TI  - Synergy of glucose and growth hormone signalling in islet cells through ICA512
      and STAT5.
AB  - Nutrients and growth hormones promote insulin production and the proliferation of
      pancreatic beta-cells. An imbalance between ever-increasing metabolic demands and
      insulin output causes diabetes. Recent evidence indicates that beta-cells enhance
      insulin gene expression depending on their secretory activity. This signalling
      pathway involves a catalytically inactive receptor tyrosine phosphatase, ICA512,
      whose cytoplasmic tail is cleaved on glucose-stimulated exocytosis of insulin
      secretory granules and then moves into the nucleus, where it upregulates insulin
      transcription. Here, we show that the cleaved cytosolic fragment of ICA512
      enhances the transcription of secretory granule genes (including its own gene) by
      binding to tyrosine phosphorylated signal transducers and activators of
      transcription (STAT) 5 and preventing its dephosphorylation. Sumoylation of
      ICA512 by the E3 SUMO ligase PIASy, in turn, may reverse this process by
      decreasing the binding of ICA512 to STAT5. These findings illustrate how the
      exocytosis of secretory granules, through a retrograde pathway that sustains STAT
      activity, converges with growth hormone signalling to induce adaptive changes in
      beta-cells in response to metabolic demands.

PMID- 16622423
TI  - Considering the consequences.

PMID- 16622424
TI  - New nomenclature for Fc receptor-like molecules.

PMID- 16622425
TI  - Immunology in the spotlight at the Dover 'Intelligent Design' trial.

PMID- 16622426
TI  - Contact hypersensitivity: not just T cells!

PMID- 16622427
TI  - On the TRAIL of homeostatic memory T cells.

PMID- 16622428
TI  - Opn: key regulator of pDC interferon production.

PMID- 16622429
TI  - Natural cytotoxicity receptors: influenza virus in the spotlight.

PMID- 16622430
TI  - T cells join the Blimp-1 brigade.

PMID- 16622432
TI  - Influenza and the challenge for immunology.
AB  - The continued westward dissemination of H5N1 influenza A viruses in avian
      populations and the nearly 50% mortality rate of humans infected with H5N1 are a
      source of great international concern. A mutant H5N1 virus with the capability to
      spread rapidly between humans could cause a global catastrophe. Governments have
      reacted by developing national response plans, stockpiling antiviral drugs and
      speeding up the development and approval of vaccines. Here we summarize what is
      known about the interaction between influenza A viruses and the mammalian host
      response, specifically emphasizing issues that might be of interest to the
      broader immunology community.

PMID- 16622434
TI  - Anxiety and depression after prostate cancer diagnosis and treatment: 5-year
      follow-up.
AB  - To document anxiety and depression from pretreatment till 5-year follow-up in 299
      men with localized prostate cancer. To assess, if baseline scores were predictive
      for anxiety and depression at 1-year follow-up. Respondents completed four
      assessments (pretreatment, at 6 and 12 months, and at 5-year follow-up) on
      anxiety, depression and mental health. Respondents were subdivided according to
      therapy (prostatectomy or radiotherapy) and high vs low-anxiety. Pretreatment 28%
      of all patients were classified as 'high-anxiety'; their average anxiety scores
      decreased significantly post-treatment, that is towards less anxiety. At all
      assessments, high-anxiety men treated by prostatectomy reported less depression
      than high-anxiety men treated by radiotherapy. Of men treated by radiotherapy,
      27% reported clinical significant levels of depression while 20% is expected in a
      general population. The improvement in mental health at 6-months follow-up was
      statistically significant and clinically meaningful in all respondent groups.
      Sensitivity of anxiety at baseline as a screening tool was 71% for anxiety and
      60% for symptoms of depression. We recommend clinicians to attempt early
      detection of patients at risk of high levels of anxiety and depression after
      prostate cancer diagnosis since prevalence is high. STAI-State can be a useful
      screening tool but needs further development.

PMID- 16622435
TI  - Prognostic factors affecting long-term outcomes in patients with resected stage
      IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study.
AB  - The aim was to investigate the efficacy of neoadjuvant docetaxel-cisplatin and
      identify prognostic factors for outcome in locally advanced stage IIIA (pN2 by
      mediastinoscopy) non-small-cell lung cancer (NSCLC) patients. In all, 75 patients
      (from 90 enrolled) underwent tumour resection after three 3-week cycles of
      docetaxel 85 mg m-2 (day 1) plus cisplatin 40 or 50 mg m-2 (days 1 and 2).
      Therapy was well tolerated (overall grade 3 toxicity occurred in 48% patients; no
      grade 4 nonhaematological toxicity was reported), with no observed late
      toxicities. Median overall survival (OS) and event-free survival (EFS) times were
      35 and 15 months, respectively, in the 75 patients who underwent surgery;
      corresponding figures for all 90 patients enrolled were 28 and 12 months. At 3
      years after initiating trial therapy, 27 out of 75 patients (36%) were alive and
      tumour free. At 5-year follow-up, 60 and 65% of patients had local relapse and
      distant metastases, respectively. The most common sites of distant metastases
      were the lung (24%) and brain (17%). Factors associated with OS, EFS and risk of
      local relapse and distant metastases were complete tumour resection and
      chemotherapy activity (clinical response, pathologic response, mediastinal
      downstaging). Neoadjuvant docetaxel-cisplatin was effective and tolerable in
      stage IIIA pN2 NSCLC, with chemotherapy contributing significantly to outcomes.

PMID- 16622436
TI  - Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment
      of advanced pancreatic cancer: results from two randomised controlled trials.
AB  - Gastrin has been shown to be a growth stimulant in pancreatic cancer cells.
      Gastrazole is a potent and selective gastrin receptor antagonist. Two randomised
      blinded trials were conducted to assess the effect of gastrazole in advanced
      pancreatic cancer. Patients with biopsy-proven, inoperable pancreatic carcinoma
      were recruited. Trial A compared protracted venous infusion (PVI) gastrazole with
      PVI placebo, whereas trial B compared PVI gastrazole with PVI fluorouracil (5
      FU). Eighteen patients were randomised in trial A. Gastrazole produced
      significantly better survival compared to placebo (median 7.9 months vs 4.5
      months; 1-year survival: 33 vs 11%, respectively; log rank P=0.02). No difference
      in toxicity was seen between gastrazole and placebo, except central venous
      catheter and pump complications. Ninety-eight patients were randomised in trial
      B. No significant survival difference was detected between gastrazole and 5-FU
      (median: 3.6 vs 4.2 months; 1-year survival: 13.2 vs 26.2%, respectively; log
      rank P=0.42). Toxicity of gastrazole was mild with significantly less diarrhoea
      (P=0.03), stomatitis (P<0.001) and hand- foot syndrome (P<0.001) compared to 5
      FU. Quality of life (QoL) assessment showed similar QoL between gastrazole and 5
      FU at baseline and no significant differences occurred with treatment either
      between arms or within arms. Compared to placebo, patients with advanced
      pancreatic cancer treated with gastrazole appeared to live longer, albeit in a
      very small trial and will require confirmation with large-scale randomised data.
      However, it did not produce survival advantage over PVI 5-FU. Lack of toxicity
      for gastrazole may allow its combination with cytotoxic drugs.

PMID- 16622437
TI  - General practice vs surgical-based follow-up for patients with colon cancer:
      randomised controlled trial.
AB  - This trial examined the optimal setting for follow-up of patients after treatment
      for colon cancer by either general practitioners or surgeons. In all, 203
      consenting patients who had undergone potentially curative treatment for colon
      cancer were randomised to follow-up by general practitioners or surgeons. Follow
      up guidance recommended three monthly clinical review and annual faecal occult
      blood tests (FOBT) and were identical in both study arms. Primary outcome
      measures (measured at baseline, 12 and 24 months were (1) quality of life, SF-12;
      physical and mental component scores, (2) anxiety and depression: Hospital
      Anxiety and Depression Scale and (3) patient satisfaction: Patient Visit-Specific
      Questionnaire. Secondary outcomes (at 24 months) were: investigations, number and
      timing of recurrences and deaths. In all, 170 patients were available for follow
      up at 12 months and 157 at 24 months. At 12 and 24 months there were no
      differences in scores for quality of life (physical component score, P=0.88 at 12
      months; P=0.28 at 24 months: mental component score, P=0.51, P=0.47; adjusted),
      anxiety (P=0.72; P=0.11) depression (P=0.28; P=0.80) or patient satisfaction
      (P=0.06, 24 months). General practitioners ordered more FOBTs than surgeons (rate
      ratio 2.4, 95% CI 1.4-4.4), whereas more colonoscopies (rate ratio 0.7, 95% CI
      0.5-1.0), and ultrasounds (rate ratio 0.5, 95% CI 0.3-1.0) were undertaken in the
      surgeon-led group. Results suggest similar recurrence, time to detection and
      death rates in each group. Colon cancer patients with follow-up led by surgeons
      or general practitioners experience similar outcomes, although patterns of
      investigation vary.

PMID- 16622438
TI  - Pharmacoeconomic analysis of adjuvant oral capecitabine vs intravenous 5-FU/LV in
      Dukes' C colon cancer: the X-ACT trial.
AB  - Oral capecitabine (Xeloda) is an effective drug with favourable safety in
      adjuvant and metastatic colorectal cancer. Oxaliplatin-based therapy is becoming
      standard for Dukes' C colon cancer in patients suitable for combination therapy,
      but is not yet approved by the UK National Institute for Health and Clinical
      Excellence (NICE) in the adjuvant setting. Adjuvant capecitabine is at least as
      effective as 5-fluorouracil/leucovorin (5-FU/LV), with significant superiority in
      relapse-free survival and a trend towards improved disease-free and overall
      survival. We assessed the cost-effectiveness of adjuvant capecitabine from payer
      (UK National Health Service (NHS)) and societal perspectives. We used clinical
      trial data and published sources to estimate incremental direct and societal
      costs and gains in quality-adjusted life months (QALMs). Acquisition costs were
      higher for capecitabine than 5-FU/LV, but higher 5-FU/LV administration costs
      resulted in 57% lower chemotherapy costs for capecitabine. Capecitabine vs 5
      FU/LV-associated adverse events required fewer medications and hospitalisations
      (cost savings pound3653). Societal costs, including patient travel/time costs,
      were reduced by >75% with capecitabine vs 5-FU/LV (cost savings pound1318), with
      lifetime gain in QALMs of 9 months. Medical resource utilisation is significantly
      decreased with capecitabine vs 5-FU/LV, with cost savings to the NHS and society.
      Capecitabine is also projected to increase life expectancy vs 5-FU/LV. Cost
      savings and better outcomes make capecitabine a preferred adjuvant therapy for
      Dukes' C colon cancer. This pharmacoeconomic analysis strongly supports replacing
      5-FU/LV with capecitabine in the adjuvant treatment of colon cancer in the UK.

PMID- 16622439
TI  - HER2 expression as a potential marker for response to therapy targeted to the
      EGFR.
AB  - Since human epidermal growth factor receptor 2 (HER2) is known to participate
      with the epidermal growth factor receptor (EGFR) in mitogenic signalling, we
      hypothesised that HER2 overexpression might indicate responsiveness to EGFR
      targeted therapies. MCF7 breast cancer cells transfected with the HER2 gene were
      subcloned to establish a set of genetically related cell lines expressing graded
      levels of HER2 by immunoblot analysis. The subcloned cell lines and parental MCF7
      cells were characterised by their growth characteristics, and cell by cell
      patterns of EGFR, HER2 and HER3 expression as well as levels of phosphorylated
      mitogen-activated protein kinase (MAPK) and AKT by laser scanning cytometry
      (LSC). Growth inhibition assays were used to characterise response to EGFR
      targeted therapy, and to determine the relationship between therapeutic response
      and levels of tyrosine kinase expression. The levels of growth inhibition of
      AG1478 and of the AG1478-trastuzumab combinations were correlated with levels of
      HER2 expression among the different cell lines. Among EGFR, HER2 and HER3, HER2
      overexpression was the best single predictive marker, but combinations of two
      markers provided additional predictive information.

PMID- 16622440
TI  - Detection of occult carcinomatous diffusion in lymph nodes from head and neck
      squamous cell carcinoma using real-time RT-PCR detection of cytokeratin 19 mRNA.
AB  - The aim of the present study was to evaluate the occult lymph node carcinomatous
      diffusion in head and neck squamous cell carcinoma (HNSCC). A total of 1328 lymph
      nodes from 31 patients treated between 2004 and 2005 were prospectively evaluated
      by routine haematoxylin-eosin-safran (HES) staining, immunohistochemistry (IHC)
      and real-time Taqman reverse-transcriptase polymerase chain reaction (real-time
      RT-PCR) assay. Amplification of cytokeratin 19 (CK19) mRNA transcripts using real
      time RT-PCR was used to quantify cervical micrometastatic burden. The cervical
      lymph node metastatic rates determined by routine HES staining and real-time RT
      PCR assay were 16.3 and 36.0%, respectively (P<0.0001). A potential change in the
      nodal status was observed in 13 (42.0%) of the 31 patients and an atypical
      pattern of lymphatic spread was identified in four patients (12.9%). Moreover,
      CK19 mRNA expression values in histologically positive lymph nodes were
      significantly higher than those observed in histologically negative lymph nodes
      (P<0.0001). These results indicate that real-time RT-PCR assay for the detection
      of CK19 mRNA is a sensitive and reliable method for the detection of
      carcinomatous cells in lymph nodes. This type of method could be used to reassess
      lymph node status according to occult lymphatic spread in patients with HNSCC.

PMID- 16622441
TI  - A minimally invasive immunocytochemical approach to early detection of oral
      squamous cell carcinoma and dysplasia.
AB  - Squamous dysplasia of the oral cavity indicates increased risk of progression to
      squamous cell carcinoma (SCC). An important advance would be the development of a
      minimally invasive assay for identification of oral SCC and dysplasia. We have
      investigated the suitability in this context of immunostaining oral smears for
      minichromosome maintainance proteins (MCMs), sensitive and specific biomarkers of
      cell cycle entry. Immunohistochemical examination of 66 oral tissue samples
      showed a greater frequency of Mcm-2 expression in surface layers of
      moderate/severe dysplasia and SCC compared to benign keratosis/mild dysplasia.
      Immunocytochemistry for Mcm-2/Mcm-5 was performed on 101 oral smears.
      Conventional smears included 23 from normal mucosa, benign proliferative disease
      and mild dysplasia, all of which were MCM negative. Of 52 conventional smears of
      SCC tissue samples, 18 were inadequate. However, MCM-positive cells were present
      in 33/34 adequate samples. Of 26 liquid-based cytology smears, 19 out of 20
      smears from SCC were adequate and all were MCM positive. Six smears from benign
      lesions were adequate and MCM negative. We conclude that MCMs are promising
      markers for early detection of oral SCC and dysplasia, particularly in a liquid
      based cytology platform. Detection of MCMs would be amenable to automation and
      potentially applicable in the developing world. Further studies are now
      warranted.

PMID- 16622442
TI  - Is nonangiogenesis a novel pathway for cancer progression? A study using 3
      dimensional tumour reconstructions.
AB  - The nonangiogenic lung tumour is characterized by neoplastic cells co-opting the
      pre-existent vasculature and filling the alveoli space. 3-dimensional
      reconstruction of the tumour reveals that this particular tumour progresses
      without neovascularization and there is no major destruction of the lung's
      architectural integrity.

PMID- 16622443
TI  - HER2 (ErbB2) receptors, a potential therapeutic target in squamous cell carcinoma
      of oesophagus.

PMID- 16622445
TI  - Kazakhstan: a folate-deficient area?
AB  - OBJECTIVE: In the Republic of Kazakhstan, located in central Asia, the
      traditional diet consists mainly of meat, and vegetable intake tends to be
      deficient. This eating lifestyle may contribute to folate deficiency, which is
      closely linked to abnormal homocysteine (HCY) metabolism. SUBJECTS AND METHODS:
      In order to evaluate current folate status in the healthy Kazakh population, we
      screened serum folate and plasma HCY in 50 healthy Kazakh adults aged 20-65 years
      (KZH) and 60 healthy Japanese control subjects aged 27-65 years (JPN). RESULTS:
      Serum levels of folate were significantly lower in KZH than in JPN (3.1 vs 10.0
      ng/ml, P<0.01). Fifty of 61 (82.0%) subjects in KZH but none in JPN showed low
      concentrations of folate (<3.6 ng/ml). Plasma levels of HCY were significantly
      higher in KZH than in JPN (13.2 vs 7.8 nmol/ml, P<0.01). CONCLUSIONS: Our
      findings strongly suggest that owing to the insufficient intake of vegetables,
      folate deficiency exists in Kazakhstan. Furthermore, hyperhomocysteinemia was
      observed in this group, probably owing to the secondary effects of folate
      deficiency.

PMID- 16622446
TI  - Scientific rationality, uncertainty and the governance of human genetics: an
      interview study with researchers at deCODE genetics.
AB  - Technology development in human genetics is fraught with uncertainty, controversy
      and unresolved moral issues, and industry scientists are sometimes accused of
      neglecting the implications of their work. The present study was carried out to
      elicit industry scientists' reflections on the relationship between commercial,
      scientific and ethical dimensions of present day genetics and the resources
      needed for robust governance of new technologies. Interviewing scientists of the
      company deCODE genetics in Iceland, we found that in spite of optimism, the
      informants revealed ambiguity and uncertainty concerning the use of human genetic
      technologies for the prevention of common diseases. They concurred that
      uncritical marketing of scientific success might cause exaggerated public
      expectations of health benefits from genetics, with the risk of backfiring and
      causing resistance to genetics in the population. On the other hand, the
      scientists did not address dilemmas arising from the commercial nature of their
      own employer. Although the scientists tended to describe public fear as
      irrational, they identified issues where scepticism might be well founded and
      explored examples where they, despite expert knowledge, held ambiguous or
      tentative personal views on the use of predictive genetic technologies. The
      rationality of science was not seen as sufficient to ensure beneficial governance
      of new technologies. The reflexivity and suspension of judgement demonstrated in
      the interviews exemplify productive features of moral deliberation in complex
      situations. Scientists should take part in dialogues concerning the governance of
      genetic technologies, acknowledge any vested interests, and use their expertise
      to highlight, not conceal the technical and moral complexity involved.

PMID- 16622447
TI  - A phase II study of vinflunine in bladder cancer patients progressing after first
      line platinum-containing regimen.
AB  - A multicentre phase II trial to determine the efficacy of vinflunine as second
      line therapy in patients with advanced transitional cell carcinoma (TCC) of the
      bladder; secondary objectives were to assess duration of response, progression
      free survival (PFS) and overall survival (OS), and to evaluate the toxicity
      associated with this treatment. Patients had tumours that failed or progressed
      after first-line platinum-containing regimens for advanced or metastatic disease,
      or had progressive disease after platinum-containing chemotherapy given with
      adjuvant or neoadjuvant intent. Response and adverse events were assessed
      according to WHO criteria and NCI-CTC (version 2), respectively. Out of 51
      patients treated with 320 mg m(-2) of vinflunine, nine patients responded to the
      therapy yielding an overall response rate of 18% (95% CI: 8.4-30.9%), and 67%
      (95%CI: 52.1-79.3%) achieved disease control (PR+SD). Of note, responses were
      seen in patients with relatively poor prognostic factors such as a short (<12
      months) interval from prior platinum therapy (19%, including an 11% response rate
      in those progressing <3 months after platinum treatment), prior treatment for
      metastatic disease (24%), prior treatment with vinca alkaloids (14%) and visceral
      involvement (20%). The median duration of response was 9.1 months (95% CI: 4.2
      15.0) and the median PFS was 3.0 months (95% CI: 2.4-3.8). The median OS was 6.6
      months (95% CI: 4.8-7.6). The main haematological toxicity was grade 3-4
      neutropenia, observed in 67% of patients (42% of cycles). Febrile neutropenia was
      observed in five patients (10%) and among them two were fatal. Constipation was
      frequently observed (but was manageable and noncumulative) and was grade 3-4 in
      only 8% of patients. The incidence of grade 3 nausea and vomiting was very low (4
      and 6% of patients, respectively). Neither grade 3-4 sensory neuropathy nor
      severe venous irritation was observed. Moreover, and of importance in this
      particular study population, no grade 3-4 renal function impairment was observed.
      Vinflunine is an active agent for the treatment of platinum-pretreated bladder
      cancer, and these results warrant further investigation in phase III trials,
      either as monotherapy or in combination with other agents as treatment of
      advanced/metastatic TCC of the bladder.

PMID- 16622448
TI  - Childhood leukaemia incidence around French nuclear installations using
      geographic zoning based on gaseous discharge dose estimates.
AB  - The present study investigated for the first time the incidence of childhood
      leukaemia (1990-2001) around French nuclear installations using a geographic
      zoning based on estimated doses to the red bone marrow due to gaseous radioactive
      discharges. The observed number of cases of acute leukaemia (O=750) in 40 km2
      centred on 23 French nuclear installations between 1990 and 2001 was lower than
      expected (E=795.01), although not significantly so (standardised incidence ratio
      SIR=0.94, 95% confidence interval=(0.88-1.01)). In none of the five zones defined
      on the basis of the estimated doses was the SIR significantly >1. There was no
      evidence of a trend in SIR with the estimated doses for all the children or for
      any of the three age groups studied. This study confirmed that there was no
      evidence of an increased incidence of childhood leukaemia around the 23 French
      nuclear sites.

PMID- 16622449
TI  - Role of simian virus 40 in cancer incidence in solid organ transplant patients.
AB  - Transplant recipients have an increased risk of developing cancer in comparison
      with the general population. We present here data on cancer development in
      transplanted subjects who received organs from donors whose DNA was previously
      examined for the genomic insertion of Simian Virus 40 (SV40). Active follow-up of
      387 recipients of solid organs donated by 134 donors, not clinically affected by
      cancer, was performed through the National Transplant Center (NTC). The average
      length of follow-up after transplant was 671+/-219 days (range 0-1085 days). Out
      of 134 proposed donors, 120 were utilised for organ donation. Of these, 12 (10%)
      were classified as positive for SV40 genomic insertion. None of the 41 recipients
      of organs from SV40 positive donors developed a tumour during the follow-up. In
      all, 11 recipients of organs given by SV40 negative donors developed a tumour
      (cancer incidence: 0.015 per year). In conclusion, cancer rates observed in our
      study are comparable to what reported by the literature in transplanted patients.
      Recipients of solid organs from SV40 positive donors do not have an increased
      risk of cancer after transplant. The role of SV40 in carcinogenesis in
      transplanted patients may be minimal.

PMID- 16622450
TI  - Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of
      oesophagus.
AB  - Several techniques are under development to diagnose oesophageal adenocarcinoma
      at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an
      optical diagnostic technique, for the identification and classification of
      malignant changes. However, there is no clear recognition of the biochemical
      changes that distinguish between the different stages of disease. Our aim is to
      understand these changes through Raman mapping studies. Raman spectral mapping
      was used to analyse 20-microm sections of tissue from 29 snap-frozen oesophageal
      biopsies. Contiguous haematoxylin and eosin sections were reviewed by a
      consultant pathologist. Principal component analysis was used to identify the
      major differences between the spectra across each map. Pseudocolour score maps
      were generated and the peaks of corresponding loads identified enabling
      visualisation of the biochemical changes associated with malignancy. Changes were
      noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra
      obtained from selected regions demonstrate increased levels of glycogen in the
      squamous area compared with increased DNA levels in the abnormal region. Raman
      spectroscopy is a highly sensitive and specific technique for demonstration of
      biochemical changes in the carcinogenesis of Barrett's oesophagus. There is
      potential for in vivo application for real-time endoscopic optical diagnosis.

PMID- 16622451
TI  - Absence of p300 induces cellular phenotypic changes characteristic of epithelial
      to mesenchyme transition.
AB  - p300 is a transcriptional cofactor and prototype histone acetyltransferase
      involved in regulating multiple cellular processes. We generated p300 deficient
      (p300-) cells from the colon carcinoma cell line HCT116 by gene targeting.
      Comparison of epithelial and mesenchymal proteins in p300- with parental HCT116
      cells showed that a number of genes involved in cell and extracellular matrix
      interactions, typical of 'epithelial to mesenchyme transition' were
      differentially regulated at both the RNA and protein level. p300- cells were
      found to have aggressive 'cancer' phenotypes, with loss of cell-cell adhesion,
      defects in cell-matrix adhesion and increased migration through collagen and
      matrigel. Although migration was shown to be metalloproteinase mediated, these
      cells actually showed a downregulation or no change in the level of key
      metalloproteinases, indicating that changes in cellular adhesion properties can
      be critical for cellular mobility.

PMID- 16622452
TI  - Thrombomodulin expression in colorectal carcinoma is protective and correlates
      with survival.
AB  - Thrombomodulin (TM) is an endothelial receptor that exhibits anticoagulant,
      antifibrinolytic and anti-inflammatory activity by inhibiting thrombin and
      cellular adhesion. In this study, the expression and significance of TM was
      examined in primary colorectal cancer and its prognostic implications explored.
      TM immunostaining was performed on formalin-fixed, paraffin-embedded tissue
      sections, from primary lesions of 200 patients with colorectal carcinoma.
      Institutional Ethical approval was granted and clinical data retrieved from
      patients' records. All normal colonic tissue expressed TM on endothelial cells.
      TM tumour cell expression was demonstrated in 53 (26.5%) cases and 147 (73.5%)
      showed no neoplastic cell staining. On univariate and multivariate analysis TM
      expression on tumour cells correlated significantly with tumour stage,
      differentiation, Jass score and 5 year survival. TM expression decreases as
      overall stage and tumour size increase (P=0.03). In all, 91% TM positive tumours
      were well differentiated and 85% of TM negative tumours were poorly
      differentiated (P<0.01). Five year survival rates of patients with positive and
      negative TM expression were 71 and 41%, respectively. Survival rate was poorer in
      those patients who were TM negative compared with those who were positive
      (P<0.01). A total of 101 (50.5%) of the cases were node negative. In this group,
      5 year survival rates of patients with positive and negative TM expression were
      87.5 and 37.8%, respectively, demonstrating a poorer survival rate for those who
      are node negative and TM negative at the time of surgery (P<0.001). This study
      demonstrates that loss of TM is a key indicator in tumour biology and prognosis.

PMID- 16622454
TI  - Is epirubicin effective in first-line chemotherapy of metastatic breast cancer
      (MBC) after an epirubicin-containing adjuvant treatment? A single centre phase
      III trial.
AB  - The aim of the study was to demonstrate the superiority of docetaxel and
      epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer
      patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single
      agent docetaxel 100 mg m-2 (D) with the combination of docetaxel 80 mg m-2 and
      epirubicin 75 mg m-2 (ED). The response rate (72 vs 79%), the progression-free
      survival (median 9 vs 11 months) and the overall survival (median 18 vs 21
      months) were not significantly different between the ED (n=26) and D arms (n=25),
      respectively. Leucopaenia, nausea and stomatitis were significantly worse with
      ED. In conclusion, epirubicin should not be administered in combination with
      taxanes in metastatic breast cancer patients relapsed after an anthracycline
      based adjuvant or neoadjuvant therapy.

PMID- 16622453
TI  - High exposures to bioactivated cyclophosphamide are related to the occurrence of
      veno-occlusive disease of the liver following high-dose chemotherapy.
AB  - We investigated whether the occurrence of veno-occlusive disease of the liver
      (VOD) may be associated with individual variations in the pharmacokinetics of
      high-dose cyclophosphamide. Patients received single or multiple courses of
      cyclophosphamide (1000 or 1500 mg m-2 day-1), thiotepa (80 or 120 mg m-2 day-1)
      and carboplatin (265-400 mg m-2 day-1) (CTC) for 4 consecutive days. The area
      under the plasma concentration-time curves (AUCs) were calculated for
      cyclophosphamide and its activated metabolites 4-hydroxycyclophosphamide and
      phosphoramide mustard based on multiple blood samples. Possible relationships
      between the AUCs and the occurrence of VOD were studied. A total of 59 patients
      (115 courses) were included. Four patients experienced VOD after a second CTC
      course. The first-course AUC of 4-hydroxycyclophosphamide (P=0.003) but not of
      phosphoramide mustard (P=0.101) appeared to be predictive of the occurrence of
      VOD after multiple courses. High exposures to bioactivated cyclophosphamide may
      lead to increased organ toxicity.

PMID- 16622455
TI  - A phase II study of FOLFIRI-3 (double infusion of irinotecan combined with LV5FU)
      after FOLFOX in advanced colorectal cancer patients.
AB  - In advanced colorectal cancer previously treated with oxaliplatin, efficacy of
      irinotecan-based chemotherapy is poor and the best regimen is not defined. We
      designed FOLFIRI-3 and conducted a phase II study to establish its efficacy and
      safety in advanced colorectal cancer patients previously treated with FOLFOX.
      FOLFIRI-3 consisted of irinotecan 100 mg m-2 as a 60-min infusion on day 1,
      running concurrently with leucovorin 200 mg m-2 as a 2-h infusion on day 1,
      followed by 46-h continuous infusion of 5-fluorouracil (5FU) 2000 mg m-2, and
      irinotecan 100 mg m-2 repeated on day 3, at the end of the 5FU infusion, every 2
      weeks. Sixty-five patients entered the study. The intent-to-treat objective
      response rate was 23% (95% CI 13-33%). Disease was stable in 37% of patients,
      progressed in 26% and was not assessable in 14%. From the start of FOLFIRI-3,
      median progression-free survival was 4.7 months and median survival 10.5 months.
      Main toxicities (% of patients) were grade 3-4 diarrhoea 23% and grade 4
      neutropenia 11%. FOLFIRI-3 is a promising regimen achieving high response rate
      and progression-free survival in patients previously treated with FOLFOX with a
      moderate toxicity.

PMID- 16622456
TI  - RNA interference as a key to knockdown overexpressed cyclooxygenase-2 gene in
      tumour cells.
AB  - Silencing those genes that are overexpressed in cancer and contribute to the
      survival and progression of tumour cells is the aim of several researches.
      Cyclooxygenase-2 (COX-2) is one of the most intensively studied genes since it is
      overexpressed in most tumours, mainly in colon cancer. The use of specific COX-2
      inhibitors to treat colon cancer has generated great enthusiasm. Yet, the side
      effects of some inhibitors emerging during long-term treatment have caused much
      concern. Genes silencing by RNA interference (RNAi) has led to new directions in
      the field of experimental oncology. In this study, we detected sequences directed
      against COX-2 mRNA, that potently downregulate COX-2 gene expression and inhibit
      phorbol 12-myristate 13-acetate-induced angiogenesis in vitro in a specific,
      nontoxic manner. Moreover, we found that the insertion of a specific cassette
      carrying anti-COX-2 short hairpin RNA sequence into a viral vector (pSUPER.retro)
      greatly increased silencing potency in a colon cancer cell line (HT29) without
      activating any interferon response. Phenotypically, COX-2 deficient HT29 cells
      showed a significant impairment of their in vitro malignant behaviour. Thus, the
      retroviral approach enhancing COX-2 knockdown, mediated by RNAi, proved to be an
      useful tool to better understand the role of COX-2 in colon cancer. Furthermore,
      the higher infection efficiency we observed in tumour cells, if compared to
      normal endothelial cells, may disclose the possibility to specifically treat
      tumour cells without impairing endothelial COX-2 activity.

PMID- 16622457
TI  - TRAIL inhibits angiogenesis stimulated by VEGF expression in human glioblastoma
      cells.
AB  - Tumour growth is tightly related to new blood vessel formation, tissue
      remodelling and invasiveness capacity. A number of tissular factors fuel the
      growth of glioblastoma multiforme, the most aggressive brain neoplasm. In fact,
      gene array analyses demonstrated that the proapoptotic cytokine tumour necrosis
      factor-related apoptosis-inducing ligand (TRAIL) inhibited mRNA expression of
      VEGF, along with those of matrix metalloproteinase-2 (MMP-2), its inhibitor
      tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), as well as the tumour
      invasiveness-related gene secreted protein acid rich in cysteine (SPARC) in
      different human glioblastoma cell lines. Particularly, VEGF mRNA and protein
      expression and release from glioblastoma cells were also inhibited by TRAIL. The
      latter also exerted antimitogenic effects on human umbilical vein endothelial
      cells (HUVECs). With the same cells, TRAIL inhibited new vessel formation in the
      in vitro matrigel model, as well as it exerted powerful inhibition of blood
      vessel formation induced by an angiogenic cocktail administered in subcutaneous
      pellets in vivo in the C57 mouse. Moreover, the expression of MMP-2, its
      inhibitor TIMP-2 and the tumour invasiveness-related protein SPARC were
      effectively inhibited by TRAIL in glioblastoma cell lines. In conclusion, our
      data indicate that TRAIL inhibits the orchestra of factors contributing to
      glioblastoma biological aggressiveness. Thus, the TRAIL system could be regarded
      as a molecular target to exploit for innovative therapy of this type of tumour.

PMID- 16622458
TI  - SKCG-1: a new candidate growth regulatory gene at chromosome 11q23.2 in human
      sporadic Wilms tumours.
AB  - Using arbitrary primed-PCR (AP-PCR), we have identified a novel genetic
      alteration located at chromosome 11q23.2 and this genetic alteration was common
      in 38% of the human Wilms tumour samples analysed. Further characterisation by
      cloning and sequencing of this genomic region revealed that it represents a part
      of an uncharacterised gene. We have named this gene as Sporadic Kidney Cancer
      Gene-1 (SKCG-1). Using fluorescence in situ hybridisation (FISH) approach, we
      established its localisation on the chromosome 11q23.2. Northern analysis
      revealed the transcript size of SKCG-1 of 2.09 kb and this was further confirmed
      by full-length cDNA sequence. Sequence analysis revealed an active translation
      start site (ATG sequence), a polyadenylation signal sequence (AATAAA), and an
      open reading frame (ORF) encoding a peptide of 124 amino acids in the cDNA
      sequence of SKCG-1. Analysis of genomic sequence of SKCG-1 revealed a promoter
      region containing TATA box located at -13 bp upstream of transcription start
      site. The AP-PCR, SCAR, and Southern blot analyses indicated genomic loss of SKCG
      1 in Wilms tumours. The transcript of SKCG-1 was abundantly present in brain,
      kidney, liver, testis, salivary gland, foetal brain, foetal liver, whereas
      relatively lower expression in heart, stomach, prostate and no expression in
      spleen, colon, lung, small intestine, muscle, adrenal gland, uterus, skin, PBL,
      and bone marrow was detected. The expression of this gene transcript was either
      very less or undetectable in Wilms and breast tumours compared to their matched
      uninvolved tissues. Inhibition of SKCG-1 by siRNA resulted in increased cell
      proliferation of kidney epithelial cells. Based on the presence of two
      transmembrane regions in its peptide, SKCG-1 has been predicted as a
      transmembrane protein. Thus, the findings of this study revealed (i) SKCG-1, a
      new gene located at 11q23.2 and harbouring genetic alteration in Wilms tumours,
      (ii) the presence of SKCG-1 gene transcripts in various human normal tissues and
      its lower expression or absence in Wilms and breast tumours indicate that it may
      be associated with tumour growth suppressor activity, (iii) the presence of an
      open reading frame in the cDNA sequence of SKCG-1 indicates that it has potential
      to encode a protein, (iv) increased cell growth by silencing this gene in HEK293
      cells further supports a potential role of this gene in growth of kidney
      epithelial cells. Our findings suggest that SKCG-1 may have a tumour suppressor
      role, and implicate genetic alteration in this gene as a potential oncogenic
      pathway and therapeutic target in kidney and breast cancer.

PMID- 16622459
TI  - Systematic review of factors influencing patient and practitioner delay in
      diagnosis of upper gastrointestinal cancer.
AB  - As knowledge on the causation of cancers advances and new treatments are
      developed, early recognition and accurate diagnosis becomes increasingly
      important. This review focused on identifying factors influencing patient and
      primary care practitioner delay for upper gastrointestinal cancer. A systematic
      methodology was applied, including extensive searches of the literature published
      from 1970 to 2003, systematic data extraction, quality assessment and narrative
      data synthesis. Included studies were those evaluating factors associated with
      the time interval between a patient first noticing a cancer symptom and
      presenting to primary care, between a patient first presenting to primary care
      and being referred to secondary care, or describing an intervention designed to
      reduce those intervals. Twenty-five studies were included in the review. Studies
      reporting delay intervals demonstrated that the patient phase of delay was
      greater than the practitioner phase, whilst patient-related research suggests
      that recognition of symptom seriousness is more important than recognition of the
      presence of the symptom. The main factors related to practitioner delay were
      misdiagnosis, application and interpretation of tests, and the confounding effect
      of existing disease. Greater understanding of patient factors is required, along
      with evaluation of interventions to ensure appropriate diagnosis, examination and
      investigation.

PMID- 16622460
TI  - The alpha2beta1 integrin mediates the malignant phenotype on type I collagen in
      pancreatic cancer cell lines.
AB  - Pancreatic cancer is characterised by a hallmark desmoplastic response that
      includes upregulated expression of the extracellular matrix, and type I collagen
      in particular. Recent studies indicate that pancreatic cancer cells stimulate
      type I collagen synthesis in adjacent stellate cells, and that this upregulated
      type I collagen expression promotes the malignant phenotype in tumour cells as
      defined by increased proliferation, resistance to chemically induced apoptosis,
      and increased tumorigenesis. The integrin specificity of this interaction between
      type I collagen and tumour cells was not identified, however. In the present
      study, we examined eight pancreatic cancer cell lines for adhesion,
      proliferation, and migration, on types I and IV collagen, fibronectin, laminin,
      and vitronectin, as well as integrin expression. Our results indicate, for the
      overwhelming majority of cell lines, that type I collagen promotes the strongest
      adhesion, proliferation, and migration relative to the other substrates tested.
      Utilising function-blocking monoclonal antibodies directed against particular
      integrin subunits in cell adhesion and migration inhibition assays, we
      demonstrate further that the malignant phenotype on type I collagen is mediated
      specifically by the alpha2beta1 integrin. These results identify alpha2beta1
      integrin-mediated adhesion to type I collagen as a potential therapeutic target
      in the treatment of pancreatic cancer.

PMID- 16622461
TI  - Lactate dehydrogenase is not a useful marker for relapse in patients on
      surveillance for stage I germ cell tumours.
AB  - As part of surveillance protocols for stage I germ cell tumours, many centres
      routinely measure human chorionic gonadotrophin (HCG), alpha feto-protein (AFP)
      as well as lactate dehydrogenase (LDH). In conjunction with regular imaging and
      clinical examination, does routine measurement of LDH add anything to our
      relapse/pick up rate? Records of 494 patients at Mount Vernon Hospital who
      relapsed on surveillance between 1985 and 2005 were examined. Of the 494 patients
      who relapsed, 125 had raised LDH at the time of relapse. 112 of these had a
      concurrent rise in either AFP, HCG or both, 11 had their disease detected on CT
      before the rise in LDH, one had a clinically palpable para-aortic mass and the
      final patient complained of back pain and his retroperitoneal disease was thus
      discovered on imaging. Routine measurement of LDH in patients on surveillance for
      stage I germ cell tumours does not add to the early detection of relapse.

PMID- 16622463
TI  - Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy
      for node-positive breast cancer.
AB  - We evaluated the survival benefit, safety, feasibility, and tolerability of dose
      dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with
      node-positive primary breast cancer. Randomised patients (n=216) received DD or
      conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108)
      received epirubicin 90 mg m-2 plus paclitaxel 175 mg m-2 in four 14-day cycles,
      then cyclophosphamide 600 mg m-2, methotrexate 40 mg m-2, and fluorouracil 600 mg
      m-2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 microg kg day-1 as
      growth support in every cycle. Conventional-schedule regimen patients (n=108)
      received epirubicin 90 mg m-2 plus cyclophosphamide 600 mg m-2 in four 21-day
      cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required.
      After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD,
      33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend
      for improved disease-free survival (DFS) and overall survival (OS). Four-year
      rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven
      cycles were administered to 208 patients (96%). Rates of cycle delay,
      discontinuation, dose reduction, and adverse events were similar in both groups.
      Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported
      by filgrastim, is safe and improves survival for patients with node-positive
      breast cancer.

PMID- 16622462
TI  - Psychological effects of a low-grade abnormal cervical smear test result: anxiety
      and associated factors.
AB  - Receipt of an abnormal cervical smear result often generates fear and confusion
      and can have a negative impact on a woman's well-being. Most previous studies
      have focussed on high-grade abnormal smears. This study describes the
      psychological and psychosocial effects, on women, of having received a low-grade
      abnormal smear result. Over 3500 women recruited to TOMBOLA (Trial Of Management
      of Borderline and Other Low-grade Abnormal smears) participated in this study.
      Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS) at
      recruitment. Socio-demographic and lifestyle factors, locus of control and
      factors associated with the psychosocial impact of the abnormal smear result were
      also assessed. Women reported anxiety levels consistent with those found in
      previous studies of women with high-grade smear results. Women at highest risk of
      anxiety were younger, had children, were current smokers, or had the highest
      levels of physical activity. Interventions that focus particularly on women's
      understanding of smear results and pre-cancer, and/or directly address their
      fears about cancer, treatment and fertility might provide the greatest
      opportunity to reduce the adverse psychosocial impact of receiving a low-grade
      abnormal cervical smear result.

PMID- 16622464
TI  - A phase I and II study of 2-weekly irinotecan with capecitabine in advanced
      gastroesophageal adenocarcinoma.
AB  - We investigated 2-weekly intravenous irinotecan combined with oral capecitabine
      in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were
      escalated in chemotherapy naive or pretreated patients to establish maximum
      tolerated doses (MTD). In phase II, patients were treated at MTD as first-line
      therapy with the primary end point of RECIST response. Dose levels in phase I
      were as follows: Level 1: irinotecan 150 mg m-2 on day 1; capecitabine 850 mg m-2
      12-hourly on days 1-9. Level 2: as level 1 but capecitabine 1000 mg m-2. Level 3:
      as level 2 but irinotecan 180 mg m-2. Level 4: as level 3 but capecitabine 1250
      mg m-2. In phase I, 21 patients were entered. Maximum tolerated dose was level 3.
      Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In
      phase II, 31 patients were entered at level 3. During the first six cycles, 13 of
      these patients underwent dose reduction and three patients stopped treatment for
      toxicity. A further six patients stopped for progressive disease. The commonest
      grade 3-4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and
      anorexia (10%). There were no treatment-related deaths. The response rate was 32%
      (95% CI 16-52%). Median overall survival was 10 months. This regimen is active in
      gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer
      than 50% patients tolerated six cycles without modification in phase II;
      therefore, modification of these doses is recommended for further study.

PMID- 16622465
TI  - Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD
      72000) combined with gemcitabine in advanced pancreatic cancer.
AB  - The humanised anti-epidermal growth factor receptor (EGFR) monoclonal antibody
      matuzumab (formerly EMD 72000) is active against pancreatic cancer in preclinical
      studies. This phase I study assessed the safety and potential benefit of combined
      treatment with matuzumab and standard-dose gemcitabine. Three groups of
      chemotherapy-naive advanced pancreatic adenocarcinoma patients (n=17) received
      escalating doses of matuzumab (400 mg weekly, 800 mg biweekly, or 800 mg weekly)
      and gemcitabine (1000 mg m-2 weekly in weeks 1-3 of each 4-week cycle). Toxicity,
      antitumour activity, pharmacokinetic (PK) parameters, and pharmacodynamic (PD)
      markers in skin biopsies were evaluated. Severe treatment-related toxicities were
      limited to grade 3 neutropenia (n=3), leucopenia (n=1), and decreased white blood
      cell count (n=1). Common study drug-related adverse events were skin toxicities
      (grade 2=6, grade 1=7) and fever (grade 1=4). Matuzumab inhibited phosphorylated
      EGFR and affected receptor-dependent signalling and transduction; effects were
      seen even in the lowest-dose group. Pharmacokinetic data were consistent with
      results of matuzumab monotherapy. Partial response (PR) or stable disease
      occurred in eight of 12 evaluated patients (66.7%), with three PRs among six
      evaluated patients in the group receiving 800 mg weekly. Matuzumab in
      biologically effective doses with standard gemcitabine therapy appears well
      tolerated. The combination is feasible and may have enhanced activity.

PMID- 16622466
TI  - Oestrogen receptor beta and neoadjuvant therapy with tamoxifen: prediction of
      response and effects of treatment.
AB  - In order to elucidate the relative importance of oestrogen receptor (ER)alpha,
      ERbeta and an ERbeta variant (ERbeta2/betacx) in the response of breast cancers
      to tamoxifen, tumour levels of each receptor were assessed in 36 patients before
      and after 3 months of neoadjuvant treatment with tamoxifen (20 mg daily). All
      patients were postmenopausal women presenting with large ERalpha-positive breast
      cancers. Clinical response to treatment was assessed by tumour volume changes as
      determined from sequential ultrasounds and pathological response by comparison of
      the tumour morphology before and after treatment. Of 33 cases, 23 (70%) were
      classified as having a clinical response and 16 (48%) as having a response
      pathologically. All tumours stained positively for ERalpha and ERbeta and 15 out
      of 33 (45%) for ERbeta2/betacx. There were no significant differences in
      quantitative expression of any receptor between tumours that subsequently
      responded and that did not, whether response was assessed clinically or
      pathologically. Tamoxifen treatment was associated with a decrease in ERalpha,
      but an increase was the most frequent change (17 out of 33) in ERbeta, and no
      consistent change was evident in staining of the ERbeta2/betacx variant. In
      summary, ERbeta1 and ERbeta2/betacx variant protein are detected in ERalpha
      positive breast tumours but their expression is not associated with a response to
      tamoxifen. Differential changes in ERalpha and ERbeta were seen with treatment.

PMID- 16622467
TI  - Phase II study of irinotecan combined with carboplatin in previously untreated
      small-cell lung cancer.
AB  - To determine the efficacy and toxicity of irinotecan combined with carboplatin,
      we conducted a phase II trial. Eligibility criteria were: chemotherapy-naive,
      small-cell lung cancer (SCLC), good performance status (PS: 0-2), age<or=75
      years, and adequate organ function. The patients' characteristics were:
      male/female=56/5; PS 0/1/2=19/38/4; median age (range)=68 years(51-75 years);
      limited disease (LD)/extensive disease (ED)=27/34. The patients received
      irinotecan (50 mg m-2) on days 1, 8, and 15, and carboplatin (AUC 5, Chatelut
      formula) on day 1 every 4 weeks. In total, 61 patients were eligible and all were
      evaluated. In all, 31 patients were treated with four or more courses of
      chemotherapy. Of the patients, 17 showed a complete response (CR), 34 showed a
      partial response (PR), nine had stable disease (SD), and one had progressive
      disease (PD). The overall response rate was 84% (95% confidence interval (CI), 72
      91%; LD 89%, ED 79%) and the CR rate was 28% (95%CI, 17-41%; LD 37%, ED 21%). The
      median time to tumour progression was 6.1 (LD 6.4, ED 5.4) months. The medial
      survival time was 15.0 (LD 20.0, ED 9.7) months, and the 2-year and 5-year
      survival rates were 31.1% (LD 48.1%, ED 17.7%) and 9.5% (LD 11.1%, ED 5.9%),
      respectively. Grade 3 or 4 leucopenia, neutropenia, thrombocytopenia, anaemia,
      and diarrhoea occurred in 33, 74, 41, 39, and 13% of cases, respectively. In
      conclusion, the combination of irinotecan and carboplatin is an active and well
      tolerated regimen in cases of SCLC.

PMID- 16622468
TI  - Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a
      phase I-II study.
AB  - The aim of this study was to evaluate feasibility and toxicity of escalating
      doses of epirubicin and paclitaxel plus fixed dose of etoposide and to define the
      activity of the triplet in extensive disease small-cell lung cancer. Thirteen
      patients entered the phase I study: the maximum tolerated doses were epirubicin
      (EpiDX) 90 mg m-2 and paclitaxel (P) 175 mg m-2 with febrile neutropenia as dose
      limiting toxicity. The recommended schedule for this regimen for the phase II
      study was EpiDX 75 mg m-2, P 175 mg m-2, etoposide (E) 100 mg m-2 intravenous
      (fixed dose) days 1-3 with courses repeated every 21 days. The prophylactic use
      of colony-stimulating factors (CSFs) was not allowed. Twenty patients entered the
      phase II trial: median age was 61 years (range 50-70), median Eastern Cooperative
      Oncology Group performance status 0 (0-2); nine patients had visceral disease and
      17 had more than two metastatic sites. A total of 100 courses were administered
      with a median of 5 (range 1-6) per patients. Main toxicity (NCI-CTC) was
      myelosuppression: neutropenia grades 3 and 4 in 16 and 35% of the courses,
      respectively. Seven episodes of febrile neutropenia were documented and one
      patient required hospital admission. Nonhaematological toxicity was moderate.
      Seven out of 19 evaluable patients achieved a complete response (37%), nine
      patients (47.3%) a partial response with an overall response rate of 84.2% (95%
      confidence interval=60.4-96.6). In this poor prognostic population of patients
      the triplet epirubicin/paclitaxel/etoposide showed high antitumour activity with
      mild nonhaematological side effects. The use of CSFs should be able to improve
      the haematological profile.

PMID- 16622470
TI  - Single-locus sex determination in the parasitoid wasp Cotesia glomerata
      (Hymenoptera: Braconidae).
AB  - The parasitoid Cotesia glomerata usually produces female-biased sex ratios in the
      field, which are presumably caused by inbreeding and local mate competition
      (LMC); yet, sibling mating increases the production of males, leading to the male
      biased sex ratio of broods in the laboratory. Previous studies have suggested
      that the sex allocation strategy of C. glomerata is based on both partial LMC in
      males and inbreeding avoidance in females. The current study investigated the
      presence of single-locus complementary sex determination (sl-CSD) as a sex
      determining mechanism in this species through inbreeding experiment, cytological
      examination and microsatellite analysis. Cytological examination detected diploid
      males in nine of 17 single pairs of sibling mating, thus in agreement with the
      proportion of matched matings predicted by the sl-CSD model. Sex ratio shifts in
      these matched sibling matings were consistent with the sl-CSD model with less
      viable diploid males. The haploid males have a single set of maternal chromosomes
      (n = 10), whereas diploid males possess a double set of chromosomes (2n = 20).
      Microsatellite analyses confirmed that diploid males produced from the matched
      matings inherited segregating genetic materials from both parents. Thus, this
      study provides the first solid evidence for the presence of sl-CSD as a sex
      determining mechanism in the braconid genus Cotesia.

PMID- 16622469
TI  - ATM haplotypes and breast cancer risk in Jewish high-risk women.
AB  - While genetic factors clearly play a role in conferring breast cancer risk, the
      contribution of ATM gene mutations to breast cancer is still unsettled. To shed
      light on this issue, ATM haplotypes were constructed using eight SNPs spanning
      the ATM gene region (142 kb) in ethnically diverse non-Ashkenazi Jewish controls
      (n=118) and high-risk (n=142) women. Of the 28 haplotypes noted, four were
      encountered in frequencies of 5% or more and accounted for 85% of all haplotypes.
      Subsequently, ATM haplotyping of high-risk, non-Ashkenazi Jews was performed on
      66 women with breast cancer and 76 asymptomatic. One SNP (rs228589) was
      significantly more prevalent among breast cancer cases compared with controls
      (P=4 x 10(-9)), and one discriminative ATM haplotype was significantly more
      prevalent among breast cancer cases (33.3%) compared with controls (3.8%), (P< or
      =10(-10)). There was no significant difference in the SNP and haplotype
      distribution between asymptomatic high-risk and symptomatic women as a function
      of disease status. We conclude that a specific ATM SNP and a specific haplotype
      are associated with increased breast cancer risk in high-risk non-Ashkenazi Jews.

PMID- 16622471
TI  - Climatic adaptation of Drosophila buzzatii populations in southeast Australia.
AB  - Variation in 19 traits possibly relevant for thermal adaptation was studied in 11
      populations of Drosophila buzzatii collected in southeast Australia. Using
      stepwise multiple regression, the variation was compared to variation in
      geographic coordinates and to a set of climatic variables estimated for each
      collection site. For 13 of the traits, a significant part of the variation was
      explained by climatic variables and/or geographic coordinates, suggesting
      directional selection for adaptation to the environment in the majority of traits
      studied. In 10 of the traits, both geographic coordinates and climatic variables
      explained significant proportions of the variation, with R2 ranging from 0.075 to
      0.58. Although larvae, pupae and adults of D. buzzatii share a common habitat,
      the measured traits were not correlated across life stages and gender. Also,
      there seemed to be special conditions in marginal populations near species
      borders, giving rise to nonlinear relations with latitude. Climate apparently
      does influence the adaptive evolution of the traits studied, but they also are
      affected by other factors that vary with latitude, longitude and distance to
      coast. These results highlight the complex challenges imposed by the environment
      on the adaptive process.

PMID- 16622472
TI  - Speciation: A new role for reinforcement.

PMID- 16622473
TI  - Spatiotemporal structure of genetic variation of a spreading plant metapopulation
      on dynamic riverbanks along the Meuse River.
AB  - Long-distance seed dispersal is a crucial determinant of within-population
      genetic variability and among-population genetic differentiation in plant
      metapopulations undergoing recurrent local extinctions and (re-)colonization. We
      investigated the spatial and temporal structure of genetic variation in a
      metapopulation of Sisymbrium austriacum located along a dynamic river system
      using dominant AFLP markers. Data on riverbank dynamics and colonization history
      allowed separating populations based on their age (< or =5 vs >5 years old).
      Bayesian analysis of population genetic structure indicated that populations were
      significantly differentiated from each other, but Mantel tests revealed that
      there was no relationship between pairwise geographic and genetic distances,
      suggesting that long-distance seed dispersal partly determines spatial genetic
      structure. Recent populations were less differentiated from each other than old
      populations. Analysis of molecular variance (AMOVA) indicated that both spatial
      factors and population age significantly determined genetic diversity, the
      effects of age being more important than spatial location. Clustering analysis
      revealed five large clusters, which were related primarily to population age and
      to a minor extent to geographical location. Our results indicate that the
      recurrent formation and destruction of riverbank habitats following peak flow
      events have a large impact on genetic diversity of riparian plant species.

PMID- 16622474
TI  - Gene flow's effect on the genetic architecture of a local adaptation and its
      consequences for QTL analyses.
AB  - This paper uses computer simulations to determine how gene flow between
      populations affects (1) the genetic architecture of a local adaptation and (2)
      properties of alleles segregating in quantitative trait locus (QTL) mapping
      populations. Results suggest that the average magnitude of an allele that causes
      a phenotypic difference between populations declines as the migration rate
      increases, but with an increase in migration, alleles of larger magnitude cause
      proportionally more of the phenotypic difference between populations. Gene flow
      between populations that are used in a QTL study tends to cause the average
      magnitude and percent variance explained (PVE) of an allele in a mapping
      population to increase. Thus, although the average magnitude of an allele causing
      a difference declines with migration the average magnitude or PVE of an allele in
      a QTL mapping population may increase. The reason is that the probability an
      allele is sampled for a QTL mapping population is in direct proportion to its
      frequency and alleles of larger magnitude tend to segregate at relatively higher
      frequencies than alleles of smaller effect with an increased migration. As the
      rate of gene flow between populations increases, the proportion of the phenotypic
      difference explained by alleles that are segregating in a QTL mapping population
      (and therefore potentially detected) decreases. Lastly, results suggest QTL
      alleles of large effect (>20% PVE) should be commonly found, provided the
      divergence time between populations is not too long or optima of populations are
      not too far apart.

PMID- 16622475
TI  - Gametophytic self-incompatibility in Lycium parishii (Solanaceae): allelic
      diversity, genealogical structure, and patterns of molecular evolution at the S
      RNase locus.
AB  - We characterized allelic diversity at the locus controlling self-incompatibility
      (SI) for a population of Lycium parishii (Solanaceae) from Organ Pipe National
      Monument, Arizona. Twenty-four partial sequences of S-RNase alleles were
      recovered from 25 individuals. Estimates of allelic diversity range from 23 to 27
      alleles and, consistent with expectations for SI, individuals are heterozygous.
      We compare S-RNase diversity, patterns of molecular evolution, and the
      genealogical structure of alleles from L. parishii to a previously studied
      population of its congener L. andersonii. Gametophytic SI is well characterized
      for Solanaceae and although balancing selection is hypothesized to be responsible
      for high levels of allelic divergence, the pattern of selection varies depending
      on the portion of the gene considered. Site-specific models investigating
      patterns of selection for L. parishii and L. andersonii indicate that positive
      selection occurs in those regions of the S-RNase gene hypothesized as important
      to the recognition response, whereas positive selection was not detected for any
      position within regions previously characterized as conserved. A 10-species
      genealogy including S-RNases from a pair of congeners from each of five genera in
      Solanaceae reveals extensive transgeneric evolution of L. parishii S-RNases.
      Further, within Lycium, the Dn/Ds ratios for pairs of closely related alleles for
      intraspecific versus interspecific comparisons were not significantly different,
      suggesting that the S-RNase diversity recovered in these two species was present
      prior to the speciation event separating them. Despite this, two S-RNases from L.
      parishii are identical to two previously reported alleles for L. andersonii,
      suggesting gene flow between these species.

PMID- 16622477
TI  - Functional signatures in antiviral T-cell immunity for monitoring virus
      associated diseases.
AB  - At present, we only have indirect knowledge of the protective role of antigen
      specific T cells in human viral infections, and it has been difficult to show a
      direct correlation between quantitative and qualitative measures of T-cell
      immunity and virus-associated diseases. However, as described in this Opinion
      article, recent advances in the characterization of T-cell functions and in the
      development of standardized T-cell assays have led to the identification of
      distinct functional signatures of T-cell responses that correlate with levels of
      viral replication and disease activity.

PMID- 16622476
TI  - Adoptive immunotherapy for cancer: building on success.
AB  - Adoptive cell transfer after host preconditioning by lymphodepletion represents
      an important advance in cancer immunotherapy. Here, we describe how a
      lymphopaenic environment enables tumour-reactive T cells to destroy large burdens
      of metastatic tumour and how the state of differentiation of the adoptively
      transferred T cells can affect the outcome of treatment. We also discuss how the
      translation of these new findings might further improve the efficacy of adoptive
      cell transfer through the use of vaccines, haematopoietic-stem-cell
      transplantation, modified preconditioning regimens, and alternative methods for
      the generation and selection of the T cells to be transferred.

PMID- 16622478
TI  - B-cell targeting in rheumatoid arthritis and other autoimmune diseases.
AB  - B-cell-targeted therapy for autoimmune disease emerged from theoretical
      proposition to practical reality between 1997 and 1998, with the availability of
      the B-cell-depleting monoclonal antibody rituximab. Since then, a score of
      autoantibody-associated disorders have been treated, with most convincing
      evidence of efficacy seen in subjects with rheumatoid arthritis. Several classes
      of B-cell-targeted agent are now under investigation. From the outset, a major
      goal of B-cell targeting has been the re-establishment of some form of
      immunological tolerance. In some subjects, the observed improvement of disease
      for years following therapy fuels hope that this goal might ultimately be
      achievable.

PMID- 16622479
TI  - Potent antibody therapeutics by design.
AB  - Antibodies constitute the most rapidly growing class of human therapeutics and
      the second largest class of drugs after vaccines. The generation of potent
      antibody therapeutics, which I review here, is an iterative design process that
      involves the generation and optimization of antibodies to improve their clinical
      potential.

PMID- 16622481
TI  - Proximity of schools in Detroit, Michigan to automobile and truck traffic.
AB  - Exposure to traffic-related air pollutants, which has been associated with a
      range of adverse health effects, often is represented using indirect proxies or
      surrogate exposure measures, most commonly, the proximity to busy roads. This
      study examines the proximity of grade K-12 schools to high traffic roads in Wayne
      County, Michigan, an area including the industrialized city of Detroit as well as
      outlying urban and suburban communities. Unlike earlier studies, commercial and
      non-commercial traffic is distinguished, and effects of school type (public,
      charter, private), socio-economic variables, demographic factors, and mapping
      errors are evaluated. We find that total traffic flow, as measured by annual
      average daily traffic (AADT), does not reflect the substantial differences
      between trucking and commuting routes. Thus, AADT alone may inadequately capture
      traffic-related exposures, especially given the large differences between diesel
      and gasoline emissions. Based on close proximity (school-road distance < or = 150
      m) to heavy traffic (AADT > or = 50,000), 4.9% of the 845 Wayne County schools
      are traffic exposed at school. In the urban core area, 7.2% of schools and 7.6%
      of students are traffic exposed at school. A larger proportion of grade 7-12
      students in public schools are exposed than K-6 students. Considering truck
      emissions, 2.8% of the schools are within 150 m of roads with 5000 or more trucks
      per day. In Wayne County, students attending schools near high traffic roads are
      more likely to be Black or Hispanic, to be enrolled in a meal program, and to
      reside in a poor area. Many of these results are driven by the large minority
      population in the densely populated core area of Detroit. The findings show that
      a large fraction of children have high exposures to traffic-related pollutants,
      especially in Detroit, and the need for exposure measures that account for both
      the composition and volume of traffic.

PMID- 16622483
TI  - [Nonvariceal upper gastrointestinal hemorrhage associated with nonsteroidal anti
      inflammatory drugs in Metropolitan Lima].
AB  - PURPOSE: The purpose of this study was to evaluate the frequency of upper
      gastrointestinal hemorrhage associated with nonsteroidal anti-inflammatory drugs
      (NSAIDs). METHODS: This investigation was prospective, descriptive and
      analytical. We evaluated patients with nonvariceal upper gastrointestinal
      hemorrhage in the gastroenterological services of the Edgardo Rebagliati,
      Hipolito Unanue, Dos de Mayo and Cayetano Heredia Hospitals, in Lima-Peru.
      Patients with chronic liver diseases or variceal hemorrhage were excluded. The
      statistics tests were calculated using Microsoft Excel and Epiinfo Program.
      RESULTS: Over the 13-month period a total of 117 patients were enrolled (77 men
      and 40 women); the average age was of 57.86 years (range: 14-85 years) 63 (54%)
      were taking NSAIDs; 60% were given aspirin, 28.5% ibuprofen 15.8% diclofenac (and
      15.8% naproxen; 31% were taking simultaneously various NSAIDs; 65% was over 60
      years old. More prescriptions of NSAIDs came from cardiology, internal medicine
      and rheumatology. However, 55.4% took them without having medical prescription.
      The most important risk factor was the age over 65 years (p<0.001). In our study
      the presence of cardiovascular and rheumatic diseases were significant risk
      factors (p<0.001). Gastric ulcer was more frequent in the group NSAIDs 31 (49%),
      vs 14 (26%) in the p<0.001, and the duodenal ulcer in the non-NSAIDs group 32
      (59%) vs 19 (30%) in p<0.01; the erosive gastritis were 13 (20.6%) in the NSAIDs
      group vs 18 (33%) p<0.01. There were significant clinical findings in the NSAIDs
      group with presence of ulcer syndrome and hematemesis (p<0.001). The level of
      hemoglobin and the number of transfusions was not significantly different in the
      groups. In the NSAIDs group, 35 (55 %) p<0.001. presented digestive injuries with
      no evidence of symptoms before the bleeding started. CONCLUSIONS: In this study,
      the association between nonvariceal upper gastrointestinal hemorrhage and the use
      of NSAIDs was significantly high in Lima, specially in elderly population, and
      the peptic ulcer was the most common, particularly the gastric type.

PMID- 16622484
TI  - [Intestinal parasitosis in patients with HIV-AIDS].
AB  - INTRODUCTION: Diarrhea, a common complication and one of the most important
      causes of malabsorption and malnutrition in AIDS patients. Our objective was to
      determine the parasitic causes of diarrhea in patients with HIV-AIDS at the
      Cayetano Heredia National Hospital (Lima, Peru). METHODS: We included 217 HIV
      AIDS patients who reported diarrhea between May 2002 and September 2005. We
      analyzed 1-3 stool samples per patient using six methods to detect oocysts,
      cysts, eggs and larvae of parasites. RESULTS: The average patients age was 34.5
      years (range 15-68); 75.12% were males. Patients with diarrhea during two weeks
      or more were 149/217 (68.66%). A total of 123 parasites were detected in 103/217
      patients (47.5%) 18/217 (8.3%) had mixed parasitic infections. Cryptosporidium
      spp. was the most frequent parasite detected. It was more prevalent in the group
      of patients who had diarrhea for two or more weeks than those who had diarrhea
      for less than two weeks (22.82% vs. 10.29%, p=0.029). Other frequent parasitosis
      cases were isosporidiasis (10.6%), giardiasis (8.3%) and strongyloidiasis (6.9%).
      CONCLUSION: Intestinal parasitosis is frequent in HIV-AIDS patients at the
      Cayetano Heredia National Hospital. The most common opportunistic pathogens were
      Criptosporidium spp. and Isospora belli and the most frequent non-opportunistic
      pathogens were Giardia lamblia and Strongyloidiasis stercoralis.

PMID- 16622485
TI  - [Morbidity and mortality risk factors in patients with ileal typhoid
      perforation].
AB  - OBJECTIVES: To determine the risk factors, morbidity and mortality rates and the
      types of postoperative complications in patients undergoing surgery for ileal
      typhoid perforation. MATERIAL AND METHODS: This retrospective study evaluated 126
      patients with anatomohistological diagnosis of ileal typhoid perforation treated
      at the Belen Hospital, Trujillo, Peru between 1966 and 2000. RESULTS: The average
      age of the total series was of 21.39 + 13.4 years (range 1 to 57 years); of
      which, 97 (76.98%) were male and 29 (23.02%) women (proportion M:F, 3.3:1). By
      means of univariate analysis, the morbidity was related with the absence of
      previous medical treatment (p = 0.035). The mortality was associated to time of
      perforation exceeding 48 hours (p = 00001); digestive hemorrhages (p = 0.003),
      leukocyte count (p = 0.021) fecaloid peritoneal secretion (p = 0.007) number of
      perforations (p = 0.001) and the surgical technique, that presented major
      mortality was the resection and ileostomy (48.3%; p = 0.001). The group of
      patients that presented post-surgical complications was 80.16%, of which 19.8% of
      them died. The most frequent complications were wound infections (67.3%) and
      sepsis (27.7%). In the multivariate analysis two parameters were evidenced in
      relation to morbidity: previous medical treatment (p < 0.05; OR = 2.9) and number
      of perforations (p = 0.01; OR = 6.4). With regard to mortality the significant
      statistical parameters were: low digestive hemorrhages (p = 0.02; OR = 11.4)
      leukocyte count (p < 0.008; OR = 7.9) type of operation (p = 0.03; OR = 1.8)
      peritoneal secretion (p < 0.04; OR = 3.02) and number of perforations (p = 0.008;
      OR = 4.6). CONCLUSIONS: The risk factors identified in the present series can be
      useful to elaborate a risk scale to predict a small, moderate or greater
      probability of complications and postoperative mortality.

PMID- 16622486
TI  - [Evaluation of the colonic endoscopic polypectomy in patients of the National
      Carlos Alberto Seguin Escobedo Hospital ESSALUD of Arequipa (1999-2004)].
AB  - The investigation was performed in the Carlos Alberto Seguin Escobedo National
      Hospital of Essalud-Arequipa, in 194 patients that were submitted to Colonic
      Endoscopic Polypectomy from January of 1999 to December of 2004. This study is
      observational, retrospective and transverse. The clinical histories, endoscopies
      reports and pathological anatomy reports were reviewed, taking the personal data,
      clinical symptoms, endoscopic and pathologic characteristics of the polyps;
      colonoscopies associate findings; surgical technique of polypectomies,
      complications and complementary treatment of post-polypectomy. The colonic
      endoscopic polypectomy was performed in 194 patients from 1380 colonoscopies
      (14.05 %), with more frequency in the sixth decade of life, and corresponding
      most to the masculine sex. Most of the patients did not have previous symptoms,
      and of those who had clinical manifestations the more frequent were the bleeding
      lost and changes in the intestinal rhythm. The polyps endoscopic characteristics
      found that the sessile were the more frequent and were located in rectum--sigmoid
      zone. The preponderant size was from 5 to 10mm, and mostly unique. The
      histopathology type of the polyps was adenoma, frequently with some grade of
      dysplasia. The surgical techniques for the colonic endoscopy polypectomy were
      with cold pincer and electric cut. The complications were rare. The complementary
      treatment after polypectomy was injectotherapy and surgery. Finally, our results
      were discussed and compared with other similar studies, and then we elaborated
      the conclusions and recommendations, with whom we expect to contribute to a
      better knowledge of the Colonic Endoscopy Polypectomy in our country.

PMID- 16622487
TI  - [Strongyloides stercoralis: histopathological findings of duodenal mucosa (1999
      2005)].
AB  - Strongyloidiasis is a parasitosis, which endoscopic and histopathologic
      presentations are very varied. It is mainly found in the duodenum, where the
      larva matures into adult female and induces varied patterns of inflammatory
      reactions. All histological slides with diagnosis of duodenal strongyloidiasis,
      and the description of the endoscopy report for a six year period (January 1999
      November 2005), were reviewed. The most frequent endoscopic findings were swollen
      foldings of nodular aspect Severe duodenitis (according to the Jenkins
      classification) was found in 57% of the cases, and villi atrophy was found in all
      cases, most of them Grade 4 (according to the Drutt classification). Plasma cells
      did not decrease in severe duodenitis, unlike those reported on peptic
      duodenitis. Our findings show greater commitment by our patients than those
      reported in the revised literature. We propose to study the relation between
      plasma cells, villi atrophy, severe duodenitis and strongyloides.

PMID- 16622488
TI  - [History of the Peruvian Society of Gastroenterology (part I)].
AB  - This is first part of the publication about the history of the Peruvian Society
      of Gastroenterology. The present work was published in electronic version when
      the Peruvian Society of Gastroenterology celebrated their fifty years of
      foundation. Is a must lecture for all that are involved in the Peruvian
      Gastroenterology.

PMID- 16622489
TI  - [Pharmacoeconomics and outcome research on Irritable Bowel Syndrome review of
      findings using Tegaserod].
AB  - Irritable Bowel Syndrome (IBS) is a chronic and episodic disease that affects
      14.5% of females in the United States, and its impact decreases the quality of
      life. On the other hand, IBS consumes a great part of the health budget and
      develops indirect costs by loss of work productivity. Currently Tagaserod an
      agonist of the number 4 serotonin receptors (5-HT4), indicated for IBS
      Constipation treatment, has demonstrated savings while optimizing health
      resources and improving the quality of life of patients and their work
      productivity.

PMID- 16622490
TI  - [Coexistence of Celiac Disease and autoimmune hepatitis case study and literature
      review].
AB  - The case of a patient who was initially diagnosed with Systemic Lupus
      Erythematosus, with subsequent documentation of Celiac Disease histologically and
      serologically is reported. The patient presented elevation of the
      aminotransferases, upon detection of the Celiac Disease which was initially
      attributed to the underlying disease. However, despite the complete resolution of
      her articular symptoms with a gluten-free diet, the liver chemistry abnormalities
      persisted. This led to consider an autoimmune hepatitis as the cause which was
      documented with a liver biopsy three months after the diagnosis of the celiac
      disease and under a strict gluten-free diet. Treatment with prednisone and
      azathioprine was initiated with complete normalization of aminotransferase
      levels. We present the sequence of events with the results and a review of the
      literature.

PMID- 16622491
TI  - [Concomitant gastric and pancreatic metastases from renal cell carcinoma: case
      study].
AB  - This report describes the case of a patient who underwent total gastrectomy,
      splenectomy and pancreatomy corporo-postero as a consequence of gastric and
      pancreatic metastasis from carcinoma to clear cells, five years after having
      undergone radical nephrectomy. Upper digestive bleeding was the first symptom,
      and pancreatic lesion was detected in previous CT scans. There are many
      documented cases of pancreatic metastasis, but only eight gastric metastasis in
      the last 15 years, although we did not find reports about surgical treatment for
      concomitant gastric and pancreatic injury. Surgical treatment which in some
      reports include highly complex surgeries such as gastrectomies with combined
      resections of invaded organs and pancreatoduodenectomy, are good options for
      select cases, because good survival rates have been reported.

PMID- 16622493
TI  - From the reactivity of N-heterocyclic carbenes to new chemistry in ionic liquids.
AB  - N-Heterocyclic carbenes have numerous applications in synthetic chemistry. We
      detail the reactivity and chemistry of these molecules including investigations
      into their reactions with small reagents, their use for the preparation of
      polarised azines and their potential application as NLO materials. The chemistry
      of imidazolium salts, which are related to NHCs by the addition of a proton, is
      also discussed. New chemistry for ionic liquids is also revealed.

PMID- 16622492
TI  - [Squamous cell carcinoma of the rectum and traumatic recto vaginal fistula
      relation or coincidence? Case study].
AB  - Primary squamous cell carcinoma of the rectum is rare and its cause and
      pathogenesis are not clear. Likewise, rectal squamous cell carcinoma in patients
      with rectovaginal fistula in the absence of gynecologic cancer is extremely rare.
      We report one of such cases that was diagnosed a year after an untreated
      traumatic rectovaginal fistula. We also reviewed the literature and discussed the
      probable association between both processes.

PMID- 16622495
TI  - A precursor state for formation of TiAl3 complex in reversible hydrogen
      desorption/adsorption from Ti-doped NaAlH4.
AB  - The structure of a TiAl3Hx complex for the formation of a TiAl3 binary phase that
      could play important roles in the reversible de-/hydrogenation of Ti-doped NaAlH4
      has been identified on the basis of first principles density functional theory
      studies.

PMID- 16622494
TI  - Metric engineering of supramolecular Borromean rings.
AB  - Two homologues of supramolecular Borromean rings were obtained based on the
      halogen-bonding-driven self-assembly of iodide ions with telechelic
      diiodoperfluoroalkanes.

PMID- 16622496
TI  - First example of an ice-like water hexamer boat tape structure in a
      supramolecular organic host.
AB  - A T6(2) tape of hydrogen bonded water molecules in boat cyclohexane conformation
      resides in the channel structure of a dibromophloroglucinol (DBPG) host; water
      escapes at 40-90 degrees C but is readily re-absorbed by the sponge-like apohost.

PMID- 16622498
TI  - Observations on the reaction of hydrazones with iodine: interception of the diazo
      intermediates.
AB  - The reaction of hydrazones with iodine/base leads to diazo intermediates that can
      be trapped by an internal alkene or alkyne.

PMID- 16622497
TI  - Melting point depression of ionic liquids confined in nanospaces.
AB  - A new physical method was proposed to control the liquid properties of room
      temperature ionic liquids (RT-ILs) in combination with nanoporous materials; the
      melting point of ILs confined in nanopores remarkably decreases in proportion to
      the inverse of the pore size.

PMID- 16622499
TI  - Direct synthesis of chiral aziridines from N-tert-butyl-sulfinylketimines.
AB  - The direct preparation of a range of variously substituted chiral tert
      butylsulfinylketimines was achieved in good yield (41-90%), with relatively rapid
      reaction times (4-15 hours); their synthetic application was examined through the
      reaction with the ylides derived from trimethylsulfonium iodide and S-allyl
      tetrahydrothiophenium bromide, affording convenient access to a diverse range of
      highly substituted chiral aziridines in up to 78% yield and > 90% d.e.

PMID- 16622500
TI  - Design and synthesis of a near infra-red luminescent hexanuclear Zn-Nd prism.
AB  - The use of the Schiff-base ligand N,N'-bis(5-bromo-3
      methoxysalicylidene)propylene-1,3-diamine (H2L) and 1,4-benzenedicarboxylate
      (BDC) enables the construction of the hexanuclear luminescent Zn-Nd complex
      [Zn4Nd2L4(1,4-BDC)2].[Nd(NO3)5(H2O)].Et2O.2EtOH.3H2O.

PMID- 16622501
TI  - Synthesis and characterization of novel mesoporous aluminosilicate MCM-41
      containing aluminophosphate building units.
AB  - Novel MCM-41 aluminosilicate/aluminophosphate materials that exhibit good
      mesostructural ordering have been synthesized and characterised; the synthesis of
      these silicoaluminophosphates involved the use of gel mixtures containing
      amorphous mesoporous aluminosilicate and aluminophosphate phases as precursor.

PMID- 16622502
TI  - An insulin-sensing sugar-based fluorescent hydrogel.
AB  - We have prepared a small library of amphiphiles, each comprising a polar
      carbohydrate head group attached through an N-terminal amino acid to a nonpolar
      pyrene tail group. One of these derivatives is sensitive to the presence of
      insulin in aqueous media.

PMID- 16622503
TI  - Comparing a mononuclear Zn(II) complex with hydrogen bond donors with a dinuclear
      Zn(II) complex for catalysing phosphate ester cleavage.
AB  - Introducing ligand based hydrogen bond donors to increase the activity of a
      mononuclear Zn(II) complex for catalysing phosphate ester cleavage can be a more
      effective strategy than making the dinuclear analogue.

PMID- 16622505
TI  - Polynuclear cyanoruthenate chromophores based on hexaaza-triphenylene containing
      up to twelve cyanides: photophysical and structural properties.
AB  - The complexes [Ru(CN)4(HAT)]2-, [{Ru(CN)4}2(mu2-HAT)]4- and [{Ru(CN)4}3(mu3
      HAT)]6- (HAT = hexaaza-triphenylene) contain four, eight and twelve externally
      directed cyanide ligands, respectively; they show strongly solvatochromic and
      intense MLCT absorptions, and [3]6- forms a high-dimensionality cyanide-bridged
      coordination network with Nd(III), in which Ru --> Nd energy transfer results in
      sensitised near-IR luminescence.

PMID- 16622504
TI  - En route to erucalexin: a unique rearrangement in the crucifer phytoalexin
      biosynthetic pathway.
AB  - The first biosynthetic studies revealing that both 1-methoxybrassinin and
      sinalbin B are close precursors of the phytoalexins erucalexin and 1
      methoxyspirobrassinin.

PMID- 16622506
TI  - On the spontaneous induction of chirality in the preparation of Werner's complex
      cis-[CoBr(NH3)(en)2]Br2.
AB  - The product obtained directly from the standard reaction to produce Werner's
      complex cis-[CoBr(NH3)(en)2]Br2 is shown, via structure determination from powder
      X-ray diffraction data, to be a racemic crystalline phase; implications of this
      observation in relation to previous reports that this reaction leads to
      significant enantiomeric excesses are discussed.

PMID- 16622507
TI  - Dehydration of the nanoporous coordination framework ErIII[CoIII(CN)6].4(H2O):
      single crystal to single crystal transformation and negative thermal expansion in
      ErIII[CoIII(CN)6].
AB  - Desorption of bound and unbound water molecules from the nanoporous coordination
      framework ErIII[CoIII(CN)6].4(H2O) to form the apohost, ErIII[CoIII(CN)6],
      proceeds via a single crystal to single crystal transformation in which the
      Er(III) cations change from 8- to 6-coordinate; dehydration results in a striking
      change in the thermal expansion properties.

PMID- 16622508
TI  - Synthesis and structural characterization of the first metal organic thallium
      antimonide.
AB  - The first metal organic thallium antimonide, the heterocycle [Me2TlSb(SiMe3)2]3,
      was synthesized by reaction of [Me2AlSb(SiMe3)2]3 with the Lewis acid-base adduct
      dmap-TlMe3 (dmap = 4-dimethylaminopyridine). The analogous TlBi heterocycle
      [Me2TlBi(SiMe3)2]3 couldn't be isolated due to its limited thermal stability in
      solution.

PMID- 16622509
TI  - A self assembled molecular zipper based on a perfluorophenyl-phenyl diacetylene
      motif.
AB  - The synthesis and characterization of a molecular rod consisting of a
      pentafluorophenyl and a para-dodecylphenyl subunit linked by a diacetylene and
      its large area self assembly into perfect parallel lines consisting of
      interlocked molecular rods are reported and discussed.

PMID- 16622510
TI  - The synthesis of quaternary ammonium salts from ammonium salts and dialkyl
      carbonate.
AB  - Quaternary ammonium salts were synthesized from ammonium salts and dialkyl
      carbonates over an ionic liquid catalyst 1-ethyl-3-methylimidazolium bromide.

PMID- 16622511
TI  - Molecular assembling using axial phenolate on an iron N-confused porphyrin
      complex.
AB  - The reaction of sodium phenolate and Fe(HCTPPH)Br assembles a dimeric iron(III)
      complex with a channel-like solid state packing; the intramolecular iron-to-iron
      distance of 8.864 A is the longest among the available N-confused porphyrin
      dimeric complexes.

PMID- 16622512
TI  - Enantioselective synthesis mediated by chiral crystal of achiral hippuric acid in
      conjunction with asymmetric autocatalysis.
AB  - Enantiomorphous crystals composed of achiral hippuric acid, i.e., naturally
      occurring N-benzoylglycine, have been used successfully as chiral inducers in
      enantioselective synthesis in combination with asymmetric autocatalysis to afford
      the product with extremely high enantiomeric excess.

PMID- 16622513
TI  - A tris-pyrazolylborate ligand with hemilabile O-donor groups. Examples of eta3,
      eta5, eta6 and bridging modes of bonding to Li+, Na+, K+, Tl+ and Ca2+ ions.
AB  - A tris-pyrazolylborate ligand bearing ether appendages is shown to be a potential
      hemilabile ligand based on NMR studies and structural characterization of its
      eta3, eta5, eta6, and micro-binding modes in coordination with Li+, Na+, K+, Tl+,
      and Ca2+ ions.

PMID- 16622514
TI  - An unusual dimerization of primary unsaturated alcohols catalyzed by
      RuHCl(CO)(PPh3)3.
AB  - When primary unsaturated alcohols were treated with a catalytic amount of
      RuHCl(CO)(PPh3)3 in benzene under reflux, dimerization reactions took place to
      give alpha-hydroxymethyl ketones as major product.

PMID- 16622515
TI  - A redox-active tri-star molecule: merging of TTF and HAT chemistry.
AB  - A planar pi-conjugated heteroaromatic molecule 1 has been synthesized and fully
      characterized; it combines two characteristics, a charge-transfer transition
      originating from its inherent donor-acceptor nature in its neutral state and an
      intervalence charge-transfer transition in its 1(2+) mixed-valence state.

PMID- 16622516
TI  - Fatigue-resistant photochromic dithienylethenes by controlling the oxidation
      state.
AB  - High fatigue-resistant photochromic dithienylethenes were synthesized by
      controlling the oxidation state of 1,2-bis(2-methyl-1-benzothiophene-3
      yl)perfluorocyclopentene (BTF6) and 1,2-bis(2,5-dimethylthien-3
      yl)perfluorocyclopentene (DMTF6).

PMID- 16622517
TI  - NMR diffusion and nuclear Overhauser investigation of the hydration properties of
      thymine: influence of the methyl group.
AB  - The absence of preferential hydration in thymine and its lowest water
      accessibility with respect to uracil were evidenced by NMR diffusion and HOESY
      experiments; the hydration differences observed between these pyrimidine bases
      were attributed to the electronic rather than steric properties of the methyl
      group.

PMID- 16622518
TI  - Platinum-acetylide polymer based solar cells: involvement of the triplet state
      for energy conversion.
AB  - Relatively efficient photovoltaic devices were fabricated using blends of a
      phosphorescent platinum-acetylide polymer and a fullerene (PCBM); involvement of
      the triplet excited state of the platinum-acetylide polymer in photoinduced
      charge transfer is believed to contribute to the device efficiency.

PMID- 16622519
TI  - Ochratoxin A-induced renal cortex fibrosis and epithelial-to-mesenchymal
      transition: molecular mechanisms of ochratoxin A-injury and potential effects of
      red wine.
AB  - We characterized the effect of chronic ochratoxin A (OTA) on rat kidney cortex,
      analyzing collagen content and collagen turnover and the major markers of
      epithelial-to-mesenchymal transition (EMT), such as alpha-smooth muscle actin
      (alphaSMA), cadherins, and MMP-9. Because OTA nephrotoxicity is mediated by free
      radicals, we also investigated whether antioxidants in red wine provided
      protection for the kidney and attenuated OTA-induced EMT. Collagen content,
      determined by computerized analysis of Sirius red-stained kidney sections,
      increased in OTA, OTA-wine, and OTA-EtOH treated rats. In kidney cortex
      homogenates, COL-I and COL-III mRNA levels tended to rise in OTA treated rats,
      but were similar to CT after OTA-wine and OTA-EtOH administration. TIMP-1 gene
      expression was up-regulated in OTA, OTA-wine, and OTA-EtOH treated rats. LH2b
      mRNA/COL-I mRNA was significantly up-regulated in OTA-wine and OTA-EtOH treated
      rats, compared with CT and OTA alone. TGF-beta1 signaling tended to dominate
      after OTA, OTA-wine, and OTA-EtOH. MMP-1 protein levels were not affected. OTA
      induced proMMP-9 and alphaSMA overexpression, decreases of E-cadherin and N
      cadherin, and DSC-2 up-regulation. OTA-wine caused a further, unexpected decrease
      of E- and N-cadherins and further up-regulation of OTA-induced DSC-2, while
      strongly reducing the OTA-induced increases of alphaSMA and proMMP-9.
      Posttranslational collagen modifications, such as decreased collagen degradation
      through MMP inhibition and increased collagen cross-links, seem to be key
      mechanisms leading to OTA-induced kidney cortex fibrosis. This mechanism was not
      affected by red wine in these conditions. Red wine seems to have some protective
      role against OTA-induced EMT, although without completely blocking the process
      and determining a condition in which abundant cells display an intermediate
      translational phenotype, but there are no alphaSMA or epithelial markers.

PMID- 16622520
TI  - Analysis of expressed and non-expressed IGK locus rearrangements in chronic
      lymphocytic leukemia.
AB  - Immunoglobulin kappa (IGK) locus rearrangements were analyzed in parallel on
      cDNA/genomic DNA in 188 kappa- and 103 lambda-chronic lymphocytic leukemia (CLL)
      cases. IGKV-KDE and IGKJ-C-intron-KDE rearrangements were also analyzed on
      genomic DNA. In kappa-CLL, only 3 of 188 cases carried double in-frame IGKV-J
      transcripts: in such cases, the possibility that leukemic cells expressed more
      than one kappa chain cannot be excluded. Twenty-eight kappa-CLL cases also
      carried nonexpressed (nontranscribed and/or out-of-frame) IGKV-J rearrangements.
      Taking IGKV-J, IGKV-KDE, and IGKJ-C-intron-KDE rearrangements together, 38% of
      kappa-CLL cases carried biallelic IGK locus rearrangements. In lambda-CLL, 69
      IGKV-J rearrangements were detected in 64 of 103 cases (62%); 24 rearrangements
      (38.2%) were in-frame. Four cases carried in-frame IGKV-J transcripts but
      retained monotypic light-chain expression, suggesting posttranscriptional
      regulation of allelic exclusion. In all, taking IGKV-J, IGKV-KDE, and IGKJ-C
      intron-KDE rearrangements together, 97% of lambda-CLL cases had at least 1
      rearranged IGK allele, in keeping with normal cells. IG repertoire comparisons in
      kappa- versus lambda-CLL revealed that CLL precursor cells tried many
      rearrangements on the same IGK allele before they became lambda producers.
      Thirteen of 28 and 26 of 69 non-expressed sequences in, respectively, kappa- or
      lambda-CLL had < 100% homology to germline. This finding might be considered as
      evidence for secondary rearrangements occurring after the onset of somatic
      hypermutation, at least in some cases. The inactivation of potentially functional
      IGKV-J joints by secondary rearrangements indicates active receptor editing in
      CLL and provides further evidence for the role of antigen in CLL
      immunopathogenesis.

PMID- 16622527
TI  - [Acute otitis media diagnosis in childhood].

PMID- 16622528
TI  - [Vulvar donovanosis as pseudo-elephantiasis].

PMID- 16622521
TI  - Microarray analyses of peripheral blood cells identifies unique gene expression
      signature in psoriatic arthritis.
AB  - Psoriatic arthritis (PsA) is a chronic and erosive form of arthritis of unknown
      cause. We aimed to characterize the PsA phenotype using gene expression profiling
      and comparing it with healthy control subjects and patients rheumatoid arthritis
      (RA). Peripheral blood cells (PBCs) of 19 patients with active PsA and 19 age-
      and sex-matched control subjects were used in the analyses of PsA, with blood
      samples collected in PaxGene tubes. A significant alteration in the pattern of
      expression of 313 genes was noted in the PBCs of PsA patients on Affymetrix U133A
      arrays: 257 genes were expressed at reduced levels in PsA, and 56 genes were
      expressed at increased levels, compared with controls. Downregulated genes tended
      to cluster to certain chromosomal regions, including those containing the
      psoriasis susceptibility loci PSORS1 and PSORS2. Among the genes with the most
      significantly reduced expression were those involved in downregulation or
      suppression of innate and acquired immune responses, such as SIGIRR, STAT3, SHP1,
      IKBKB, IL-11RA, and TCF7, suggesting inappropriate control that favors proin
      flammatory responses. Several members of the MAPK signaling pathway and tumor
      suppressor genes showed reduced expression. Three proinflammatory genes--S100A8,
      S100A12, and thioredoxin--showed increased expression. Logistic regression and
      recursive partitioning analysis determined that one gene, nucleoporin 62 kDa,
      could correctly classify all controls and 94.7% of the PsA patients. Using a
      dataset of 48 RA samples for comparison, the combination of two genes, MAP3K3
      followed by CACNA1S, was enough to correctly classify all RA and PsA patients.
      Thus, PBC gene expression profiling identified a gene expression signature that
      differentiated PsA from RA, and PsA from controls. Several novel genes were
      differentially expressed in PsA and may prove to be diagnostic biomarkers or
      serve as new targets for the development of therapies.

PMID- 16622529
TI  - [Foreign Bodies in Gastric Fundus with three months of evolution].

PMID- 16622530
TI  - [Value of the scientific article publication].

PMID- 16622533
TI  - [Acceptance of chemotherapy by Brazilian women with breast cancer].
AB  - INTRODUCTION: Breast cancer has the second highest incidence and is the first
      cause of death by cancer among Brazilian women. Under the physician's perspective
      chemotherapy should be indicated according to the risk benefit ratio in each
      case. However, from the Brazilian breast cancer patient's perspective this risk
      benefit ratio requires further classification. OBJECTIVE: In patients with breast
      cancer who have already received chemotherapy evaluate the minimum benefit
      considered necessary for a renewed administration and learn which factors may
      influence this decision. METHODS: we surveyed 53 patients comprising general,
      clinical and cancer related variables, as well as issues related to the minimal
      expected benefit which would induce the patient to agree to undergo chemotherapy.
      RESULTS: 75% would accept to receive chemotherapy again even if it would not
      change their probability of relapse, 50% would accept chemotherapy again, even
      though it would not increase survival rates. Similarly, 81.54% would submit once
      more to chemotherapy even though it would not increase their probability of cure.
      Acceptance of a new chemotherapy treatment yielding minimal benefits correlated
      significantly with more age, with a lower educational level and with no previous
      administration of Adriamycin. CONCLUSION: Even with a minimal benefit, the
      majority of formerly treated breast cancer patients are willing to submit to
      another chemotherapy treatment.

PMID- 16622534
TI  - [Precision and accuracy of body weight assessment in hospitalized adults].
AB  - BACKGROUND: Body weight (BW) is widely used to evaluate and manage clinical
      situations therefore assessment errors can influence the ichosen therapies.
      OBJECTIVE: To assess the variability in values of BW obtained by using different
      equipment (weight scales). METHODS: A cross sectional study was performed to
      assess BW of 360 adult patients in eight units including clinical and surgical
      specialties Three types of scales were used: a portable domestic model and a
      fixed platform model, both from the units and a portable digital model previously
      calibrated and used as standard reference equipment. Self-reported weight (SRW)
      was also compared to weight assessed with the reference equipment. The values
      were compared trough paired-samples t-test using SPSS software. RESULTS: The
      difference between weights assessed by the reference equipment and SRW was 445+/
      3.359 g (P=0.015), it was -182+/-2.323 g (P=0.140) for portable domestic scales
      and 137+/-2.412 g (P=0.218) for platform fixed scales. Values obtained from SRW,
      portable domestic scales and fixed platform scales were strongly correlated to
      the mean value of weight assessed by the reference equipment (r=0.973, r=0.987
      and r=0.986, respectively). Nevertheless, considering analyses of each patient,
      errors of magnitude greater than 500 g occurred in 78.8% of SRW, 80.6% of the
      portable domestic scales and 40% of the fixed platform scales. CONCLUSION: In
      general, the scales tested were neither accurate nor precise for measuring BW,
      considering the percentage of error in the evaluation of each patient and the
      variability observed.

PMID- 16622535
TI  - [Profile of prostate cancer at the general hospital of Porto Alegre].
AB  - OBJECTIVES: To describe prevalence and features of prostate cancer in the sample.
      METHODS: A five year long voluntary screening program was carried out in the
      "Hospital das Clinicas de Porto Alegre" with the participation of 3,056 patients
      in a cross sectional study. For statistical analysis the chi square test was
      used, considering a significance level of p < 0.05 RESULTS: Mean age of the
      sample was of 60.4 years and prevalence of prostate cancer was of 2.61%,
      increasing with age. Sensitivity and specificity of PSA were respectively 93.8%
      (CI = 85.4% to 97.7%) and 82.5% (CI = 81.1% to 83.8%), considering 4 ng/ml as the
      cut-off point for PSA. Rectal examination had a sensitivity of 60% (CI = 48.4% to
      70.6%) and a specificity of 83.3% (CI = 81.9% to 84.6%) The number of biopsies
      performed for the diagnosis of a patient with prostate cancer was 11.9 and varied
      according to age. As for clinical staging, 51.3% of patients were T1C and 83.75%
      of the tumors were clinically confined to the organ. CONCLUSION: Screening
      programs can be performed in our environment and direct to a frequent diagnosis
      of patients with prostate cancer confined to the organ.

PMID- 16622536
TI  - [Weight variation in users of the levonorgestrel-releasing intrauterine system,
      of the copper IUD and of medroxyprogesterone acetate in Brazil].
AB  - BACKGROUND: Assess weight variations in Brazilian users of the 20 microg/day
      levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena) for comparison
      with a cohort of users of the TCu 380A intrauterine device (IUD) and a cohort of
      users of the injectable contraceptive, depot-medroxyprogesterone acetate (DMPA)
      over a period of five years. METHODS: A total of 163 users of the LNG-IUS, who
      had the device inserted in 1998, were admitted to the study. At the time of
      enrollment, each woman was matched by weight (+/- 1 kg) and age (+/- 1 year) to a
      woman using a TCu 380A IUD and to another woman using DMPA. All women were
      followed up for a period of five years. Each year weight was measured and the
      body mass index (BMI, kg/m2) was calculated. RESULTS: Age of the LNG-IUS users
      was 27.0 +/- 6.7 years (mean +/- SD), while age of the copper IUD users was 28.0
      +/- 6.6 years and that of DMPA users was 26.9 +/- 6.5 years. Weight recorded at
      the onset of the study was 62.9 +/- 0.8 kg, 62.8 +/- 0.8 kg, and 62.5 +/- 0.9 kg
      (Mean +/- SD) for users of the LNG-IUS, the copper IUD, and DMPA, respectively.
      The BMI of women was initially 25.0 (+/- 0.3), 26.4 (+/- 0.3), and 25.5 (+/-
      0.4), (Mean +/- SD), for users of the LNG-IUS, copper IUD, and DMPA,
      respectively. Weight increases of 3.1 kg, 4.9 kg and 8.2 kg were observed at the
      end of the fifth year among users of the LNG-IUS, copper IUD, and DMPA,
      respectively (p = 0.009). Increase of the BMI was also observed among all groups
      (final BMI was 26.3 +/- 0.7, 28.5 +/- 0.8 and 28.7 +/- 1.3 for users of the LNG
      IUS, copper IUD and DMPA, respectively). Multivariate analysis showed that there
      was a significant association between weight increase and length of use of the
      contraceptive method and of the DMPA. CONCLUSION: The use of a LNG-IUS during
      five years caused no significant weight increase and the difference in weight was
      of the same magnitude as that of copper IUD users.

PMID- 16622537
TI  - [Random clinical comparative trial between free and directed exercise in post
      operative complications of breast cancer].
AB  - INTRODUCTION: The objective of this study was to evaluate the association among
      physiotherapy exercises performed--directed or free--in case of post-operative
      complications in women who underwent radical mastectomy or quadrantectomy with
      axillary dissection. METHODS: Sixty women were randomized. The directed group
      performed physiotherapy following a regimen of 19 exercises. The free group
      performed the exercises following the biomechanical physiological movements of
      the shoulder without a previously defined sequence or number of repetitions,
      exercises were done to the rhythm of music. RESULTS: In the average, the directed
      group remained 12.17 + 2.96 days with the drain, while the free group remained
      11.96 + 2.32 days, with no significant difference between groups. The amount of
      secretion drained during the permanence of the drain also revealed resemblance
      between groups, with an average of 1308.71 + 562.6 ml in the directed group and
      of 1391.62 + 644.65 ml in the group of free exercises. Incidences of seroma and
      dehiscence of the surgical wound did not seem to be influenced by the type of
      exercise at any of the times evaluated. In the directed group, 7.4% and 3.4% of
      the women presented with seroma on the 28th and 42nd days, respectively, while at
      the same moments of evaluation the free group presented respectively. 3.6% and
      3.6%. Incidence of dehiscence of the surgical wound also was similar in the two
      groups, in the directed group it was of 20% on the 14th day, 31% on the 28th day
      and 10.3% on the 42nd day of postoperative. In the free group the incidence was
      of 23.3% on the 14th day, of 33.3% on the 28th day and of 22.2% on the 42nd day
      of postoperative. The statistical difference observed in the averages of the hand
      and arm circumferences does not translate into clinical differences. CONCLUSION:
      The complications were not influenced f by the physiotherapy exercises performed.

PMID- 16622538
TI  - [Serological detection of anti HPV 16/18 and its association with pap smear in
      adolescents and young women].
AB  - OBJECTIVE: Verify the relation between HPV 16/18 antibodies and the association
      with cervical cytology findings in adolescents and young women. METHODS: A cross
      sectional study with 541 healthy and sexually active women from 15 to 25 years of
      age was carried on from September to November 2000. At gynecological examination,
      a cervical sample on liquid-base for cytology-testing and a blood sample for
      ELISA identification of HPV 16 and 18 antibodies were collected and sent to a
      reference laboratory in Belgium. Statistical analysis estimated the prevalence
      and prevalence ratio with a 95% confidence interval. RESULTS: Of these young
      women, 150 (27.7%) were seropositive: 79 (14.6%) to HPV 16 antibody; 35 (6.4%) to
      HPV 18 antibody and 36 (6.6%) to both HPV 16/18 antibodies. Cytological
      abnormalities were detected in 107 cases (20.5%): 63 presented with atypical
      squamous cells of undetermined significance (ASCUS), 41 were suggestive of low
      grade squamous intra-epithelial lesion (LGSIL) and 3 of high grade squamous intra
      epithelial lesion (HGSIL). Prevalence of abnormal cytology with a positive
      serology was only 1.75 times that of prevalence of abnormal cytology with a
      negative serology. Detection of abnormal cytology was not correlated with
      positive serology. CONCLUSION: Results of this study indicate a high prevalence
      of HPV 16 and 18 in young healthy women which showed no relation to the abnormal
      findings of cytology smears.

PMID- 16622540
TI  - [Ultrasonographic assessment of infantile hip by the Graf method].
AB  - BACKGROUND: Ultrasonography of the hip performed by the Graf method is widely
      accepted as an important diagnostic and treatment tool for hip dysplasia. This
      study aims to examine the reliability and reproducibility of the interpretations
      of ultrasound scans by general orthopedists. METHODS: Thirteen examiners
      evaluated five hip ultrasounds of the same normal child. The examiners measured
      alpha and beta angles according to Graf. Statistical analysis was performed by
      variance analysis (ANOVA) and agreement was calculated and expressed as the
      intraclass correlation coefficient (ICC). RESULTS: The alpha angle mean was 37.32
      degrees (11.12) and the beta angle mean was 45.05 degrees (10.49). Error of the
      intra-observer was 17.65 for the alpha angle and 17.63 for the beta. Error of the
      inter-observer was 7.68 for the alpha angle and 17.21 for the beta. ICC intra
      observer was 0.18 for the alpha angle and 0.29 for the beta. ICC inter-observer
      was -0.02 for the alpha angle and 0.3 for the beta. CONCLUSIONS: Ultrasound of
      the infantile hip using the Graf method is an important tool for the assessment
      of developmental dysplasia of the hip, however, it must be emphasized that
      preciseness of interpretation requires training and frequent use.

PMID- 16622539
TI  - [Gastrointestinal stromal tumor: a report of eight cases].
AB  - INTRODUCTION: Diagnosis and treatment of Gastrointestinal Stromal Tumor have
      changed because of recent genetic and molecular biological studies which have a
      direct impact on longer survival. METHODS: A retrospective research was carried
      out from November 1998 to July 2004 at the university and in the private clinics
      of the authors who identified GIST cases based upon positive tests to c-kit
      (CD117). RESULTS: The eight patients that were evaluated had an average age of
      53.2 and 75% were females. The most common clinical feature was abdominal mass
      (62.5%). The more frequent tumor site was the stomach (62.5%) followed by the
      small bowel (37.5%). Mean tumor size was 10.6 cm. Resection with negative
      microscopic margins was possible in all patients. Tumor recurrence occurred in
      four cases which were treated with imatinib mesilate (STI-571) with partial
      response in three cases and complete response in the other. Seven patients
      (87.5%) are alive with a mean follow-up of 33.4 months (9 to 60 months). Due to
      the limited number of patients it was not possible to correlate biological
      behavior of the tumor with its size and mitotic count. CONCLUSIONS: There was
      prevalence in the female gender. Most common tumor site was the stomach.
      Histological examinations did not disclose any correlation between tumor size and
      number of mitosis. At an average follow-up of 33.4 months, the mean survival was
      87.5%.

PMID- 16622541
TI  - [Effects of splenic surgeries on lipidogram of rats].
AB  - BACKGROUND: Although the occurrence of spleen alterations in the various forms of
      dyslipidemia, such as Gaucher's disease, has been well established, the relation
      between the spleen and lipid metabolism has not been properly studied. In order
      to contribute to the filling of this gap, in the present investigation we
      assessed experimentally the lipidogram of rats in the presence of the spleen, in
      asplenia, and after conservative spleen surgeries. METHODS: Forty female Wistar
      rats of similar weight and age were divided into 4 groups submitted to the
      following procedures: Group 1--control, with an intact spleen; Group 2--total
      splenectomy; Group 3--subtotal splenectomy, and Group 4--total splenectomy
      complemented with autogenous spleen tissue implants. Four months after the
      interventions, serum triglycerides, total cholesterol and fractions (VLDL, LDL,
      HDL) were determined. The results for the four groups were compared by analysis
      of variance followed by the Tukey-Kramer test, with the level of significance set
      at p < 0.05. RESULTS: There were no differences between groups 1, 3 and 4. In the
      animals submitted to total splenectomy, total cholesterol (p = 0.0093) and LDL
      fraction concentrations (p < 0.0001) were higher, whereas HDL fraction
      concentrations were lower (p = 0.05) than those detected in the other groups.
      There was no difference in triglycerides (p = 0.1882) or VLDL (p = 0.2030)
      between groups. CONCLUSIONS: The spleen probably plays an important role in the
      lipid metabolism of female rats and total splenectomy may be related to changes
      in cholesterol control. It is possible that preservation of spleen tissue
      prevents such metabolic disorders.

PMID- 16622542
TI  - [The National Health Surveillance Agency, ANVISA, and clinical research in
      Brazil].
AB  - Conduction of clinical trials with drugs in Brazil requires prior approval by
      Committees for Ethics in Research (CEPs) and, in certain cases, by the National
      Commission for Ethics in Research (CONEP). Approval by the National Health
      Surveillance Agency (ANVISA), through its Office for New Drugs, Research and
      Clinical Trials (GEPEC), is currently required only for drugs and medical devices
      manufactured in other countries and therefore need permission to be imported.
      This article briefly reviews the history of clinical research regulation in
      Brazil, then presents an overview of the current regulatory role of ANVISA and
      its future prospective. Major points discussed are the new forthcoming ANVISA
      regulations, with emphasis on adverse event notifications and inspections/audits
      on clinical trials and their impact on clinical research in Brazil, from the
      standpoint of the industry, university, contract research organizations,
      physicians and other health professionals. It should be stressed that to decide
      upon the licensing of new drugs ANVISA must obtain information from clinical
      trials.

PMID- 16622543
TI  - Bone marrow transplantation in patients with storage diseases: a developing
      country experience.
AB  - Bone marrow transplantation (BMT) is a therapeutic option for patients with
      genetic storage diseases. Between 1979 and 2002, eight patients, four females and
      four males (1 to 13 years old) were submitted to this procedure in our center.
      Six patients had mucopolysaccharidosis (MPS I in 3; MPS III in one and MPS VI in
      2), one had adrenoleukodystrophy (ALD) and one had Gaucher disease. Five patients
      had related and three unrelated BMT donor. Three patients developed graft versus
      host disease (two MPS I and one MPS VI) and died between 37 and 151 days after
      transplantation. Five patients survived 4 to 16 years after transplantation.
      Three patients improved (one MPS I; one MPS VI and the Gaucher disease patient),
      one patient had no disease progression (ALD) and in one patient this procedure
      did not change the natural course of the disease (MPS III).

PMID- 16622544
TI  - Clinical presentation of juvenile Huntington disease.
AB  - OBJECTIVE: To describe the clinical presentation a group of patients with
      juvenile onset of Huntington disease. METHOD: All patients were interviewed
      following a structured clinical questionnaire. Patients were genotyped for the
      trinucleotide cytosine-adenine-guanine (CAG) repeat in the Huntington Disease
      gene. High resolution brain MRI was performed in all patients. RESULTS: We
      identified 4 patients with juvenile onset of disease among 50 patients with
      Huntington disease followed prospectively in our Neurogenetics clinic. Age at
      onset varied from 3 to 13 years, there were 2 boys, and 3 patients had a paternal
      inheritance of the disease. Expanded Huntington disease allele sizes varied from
      41 to 69 trinucleotide repeats. The early onset patients presented with rigidity,
      bradykinesia, dystonia, dysarthria, seizures and ataxia. MRI showed severe volume
      loss of caudate and putamen nuclei (p=0.001) and reduced cerebral and cerebellum
      volumes (p=0.01). CONCLUSION: 8% of Huntington disease patients seen in our
      clinic had juvenile onset of the disease. They did not present with typical
      chorea as seen in adult onset Huntington disease. There was a predominance of
      rigidity and bradykinesia. Two other important clinical features were seizures
      and ataxia, which related with the imaging findings of early cortical atrophy and
      cerebellum volume loss.

PMID- 16622545
TI  - Perceptions and electric senoidal current stimulation.
AB  - OBJECTIVE: To analyze the relationship between perceptions and electrical
      senoidal current stimulation (ESCS). METHOD: The study population comprise 100
      healthy volunteers. ESCS of 5 Hz and 2 kHz were applied to the left index finger
      at one and 1.5 sensory threshold. Following each stimulus train a list of eight
      words (four related to thin fiber sensations and four related to thick fiber
      sensations) was presented to the subjects who were asked to choose the three
      words closer to the experienced sensation. Each chosen word was given a score 1;
      final results were obtained by the sum of the scores for the words related to
      thin and thick fiber systems for each situation. RESULTS: For 5 Hz ESCS at one
      and 1.5 sensory threshold thin fibers had significantly higher scores than thick
      fibers; for 2 kHz ESCS, thick fibers had significantly higher scores. CONCLUSION:
      These results show that there is a relation between different sensations and ESCS
      of different frequencies.

PMID- 16622546
TI  - Anthropometric evaluation in diabetic patients with ischemic stroke.
AB  - Strokes are one of the most common causes of mortality and long term severe
      disability. Risk factors for stroke include: age, gender, diabetes mellitus (DM),
      hypertension, and many others. OBJECTIVE: To evaluate obesity and hypertension in
      patients affected by acute ischemic stroke. METHOD: We compared the
      anthropometric variables between type II diabetic patients and non-diabetic
      patients. We evaluated a total of 60 patients, divided into two groups: 34 non
      diabetic patients and a group of 26 type II diabetic subjects. RESULTS: The
      predominance of obesity, as well as hypertension, was very high among the studied
      groups, presenting no differences among the waist-hip ratio (WHR) values of the
      study group compared to the ones of the control group. CONCLUSION: The
      predominance of obesity was very high among the studied groups and there was
      prevalence the android type obesity. There was no significative difference in the
      anthropometric evaluation by the measurement of WHR and the waist in the groups.

PMID- 16622547
TI  - A functional electric orthesis on the paretic leg improves quality of life of
      stroke patients.
AB  - CONTEXT: Hemiparesia changes quality of life of patients with stroke making
      difficult a normal life. OBJECTIVE: To evaluate the effect of Functional Eletric
      Orthesis (FEO) applied over the paretic leg in the quality of life of stroke
      patients. METHOD: The quality of life of 50 stroke patients of Associacao de
      Assistencia a Crianca Deficiente (AACD) was evaluated with SF-36 questionnaire
      before and after the treatment with a FEO for rehabilitation of walking. We
      analyzed data according to gender and affected hemisphere. RESULTS: The average
      values from all domains of SF-36 improved significantly (p<0.001). Female
      patients improved more than male in Emotional Domain (p=0.04) and presented a
      trend to be better regarding Bodily Pain and Social Functioning. Patients with
      right hemiparesia improved more than those with left hemiparesia (p=0.02).
      CONCLUSION: FEO over a paretic leg is efficient to improve quality of life of
      stroke patients, mainly Physical Functioning.

PMID- 16622548
TI  - S100B protein related neonatal hypoxia.
AB  - Biochemical markers have played an increasingly relevant role in the assessment
      of neonatal asphyxia. The S100B protein is particularly important in research
      conducted in this field. The purpose of this study was to underline the
      importance of the S100B protein in the assessment of term newborn infants with
      hypoxic-ischemic encephalopathy, as well as to relate it to other substances also
      involved in the ischemic process. An assessment was made from September 2003 to
      October 2004 of 21 term newborn infants who developed hypoxic-ischemic
      encephalopathy. Samples were collected on the 1st and 4th day of life and S100B
      protein and lactate concentrations were calculated using the immune cytochemical
      method. A positive relationship was found between the two substances.
      Additionally, a comparison between the two substances showed a statistically
      significant correlation.

PMID- 16622549
TI  - Prognostic relevance of risk factors for obstetrical brachial plexopathy.
AB  - We did a case-control study to verify if the birthweight, forceps delivery or
      perinatal asphyxia have any significant effect on the prognosis of obstetrical
      brachial plexopathy. Group A was composed of 25 infants who completely recovered
      at the age of 6 months. Group B was composed of 21 infants who were still not
      able to remove a blindfold from the face with the affected limb in the sitting
      position at the age of 12 months. There was no statistical difference of the
      median birthweight or median first minute Apgar score between the groups. There
      was also no relation between birthweight higher than 4000 g, first minute Apgar
      score lower than 6 or forceps delivery with a poor prognosis.

PMID- 16622550
TI  - Comparison between two tests of delayed recall for the diagnosis of dementia.
AB  - Diagnosis of dementia is a challenge in populations with heterogeneous
      educational background. OBJECTIVE: To compare the accuracies of two delayed
      recall tests for the diagnosis of dementia in a community with high proportion of
      illiterates. METHOD: The delayed recall of a word list from the CERAD battery (DR
      CERAD) was compared with the delayed recall of objects presented as line drawings
      from the Brief Cognitive Screening Battery (DR-BCSB) using ROC curves. Illiterate
      (23 controls and 17 patients with dementia) and literate individuals (28 controls
      and 17 patients with dementia) were evaluated in a community-dwelling Brazilian
      population. RESULTS: The DR-BCSB showed higher accuracy than the DR-CERAD in the
      illiterate (p=0.029), similar accuracy in the literate individuals (p=0.527), and
      a trend for higher accuracy in the entire population (p=0.084). CONCLUSION: the
      DR-BCSB could be an alternative for the diagnosis of dementia in populations with
      high proportion of illiterates.

PMID- 16622551
TI  - Epidemiology of primary and secondary headaches in a Brazilian tertiary-care
      center.
AB  - OBJECTIVE: To analyze the demographic features of the population sample, the time
      of headache complaint until first consultation and the diagnosis of primary and
      secondary headaches. METHOD: 3328 patients were analyzed retrospectively and
      divided according to gender, age, race, school instruction, onset of headache
      until first consultation and diagnosis(ICHD-II, 2004). RESULTS: Sex ratio
      (Female/Male) was 4:1, and the mean age was 40.7+/-15 years, without statistical
      differences between sexes. Approximately 65% of the patients were white and 55%
      had less than eight years of school instruction. Headache complaint until first
      consultation ranged from 1 to 5 years in 32.99% patients. The most prevalent
      diagnosis were migraine (37.98%), tension-type headache-TTH (22.65%) and cluster
      headache (2.73%). CONCLUSION: There are few data on epidemiological features of
      headache clinic populations, mainly in developing countries. According to the
      literature, migraine was more frequent than TTH. It is noteworthy the low school
      instruction of this sample and time patient spent to seek for specialized
      attention. Hypnic headache syndrome was seen with an unusual frequency.

PMID- 16622552
TI  - Comparative clinical study of preterm and full-term newborn neonatal seizures.
AB  - OBJECTIVE: To compare the characteristics of neonatal seizures between preterm
      and full-term infants in intensive care unit. METHOD: A prospective study was
      developed with 104 high-risk newborn, 30 preterm and 74 full-term infants, with
      clinical seizures. The dependent variable was gestational age. STATISTICAL
      ANALYSES: Fisher's exact test, odds-ratio and Mann Whitney U test. RESULTS: There
      were significant differences (p<0.05): i) Premature neonates develop neonatal
      seizures later, probably related to the etiologies of the seizures; ii)
      Etiologically, there is a predominance of peri-intraventricular hemorrhage in
      preterm and of asphyxia in full term neonates; iii) Clonic seizures are most
      frequent in preterm and subtle seizures in full term neonates. CONCLUSION:
      Although the study had a clinical basis, it was possible to identify differences
      when the dependent variable was gestational age.

PMID- 16622553
TI  - Immunomodulatory treatment in multiple sclerosis: experience at a Brazilian
      center with 390 patients.
AB  - Since 1993 the Federal Drug Administration approved the use of immunomodulatory
      therapy in multiple sclerosis (MS), modifying the natural course of disease, as
      demonstrate our experience in treatment of MS patients at the MS Treatment Center
      (CATEM). OBJECTIVE: To evaluate patient behavior using immunomodulatory therapy
      for a period of five years treatment. METHOD: We selected 390 patients in CATEM
      with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with
      relapses. RESULTS: At initial treatment 292 (61.5%) patients presented RRMS, 98
      (20.6%) SPMS with relapses, 27 SPMS (5.6%) and 58 (12.1%) primary progressive MS
      (PPMS). In RRMS 182 (62.5%) used the interferon beta 1a SC, 15 (5.2%) interferon
      beta 1a IM, 85 (29%) interferon beta 1b and 10 (3.3%) glatiramer acetate. In SPMS
      63 (64.3%) used interferon beta 1a SC, 4 (4.1%) interferon beta 1a IM and 31
      (31.4%) interferon beta 1b. We observed that in this period 195 (50%) migrated
      between drugs, 35 (9%) gave up therapy and 160 (41%) continued the initial
      therapy. CONCLUSION: Stopping the immunomodulatory therapy emerges as a problem
      in the second year of treatment and it can be a subset of interferon non
      responsive or development of neutralizing antibodies.

PMID- 16622554
TI  - Influence of the cerebrospinal fluid laboratory parameters in the ELISA test for
      neurocysticercosis using a total cysticerci antigen.
AB  - To evaluate if the cerebrospinal fluid (CSF) parameters may influence the
      cysticercosis immunoreactivity response in the CSF. CSF samples of 109 patients
      were analyzed and classified in three groups, according to the neurological
      manifestations and the reactivity in antibody-enzyme linked immunosorbent assay
      (Ab-ELISA) testing in CSF for neurocysticercosis (NC): group A, 18 patients with
      neurological disorders compatible with NC and reactive Ab-ELISA in CSF for NC;
      group B, 50 patients with neurological disorders non-compatible with NC and
      reactive Ab-ELISA for NC; group C, 41 patients with neurological disorders non
      compatible with NC and non-reactive Ab-ELISA in CSF for NC. The CSF analysis in
      group A was compatible with NC. The group B in comparison to the groups A and C
      presents higher frequency and intensity of hypercytosis, presence of red blood
      cells in CSF, protein concentration and immunological reactive test for other
      etiological agents (p<0.05). Based on the present data, we suggest that the
      inflammatory process and high protein concentration may determine false positive
      reactions in the Ab-ELISA test for NC in the CSF.

PMID- 16622555
TI  - Expression of p53, Ki-67 and c-erb B2 in growth hormone-and/or prolactin
      secreting pituitary adenomas.
AB  - The subcellular events implicated on the formation and behavior of pituitary
      adenomas are not fully understood. In this study we investigated the presence of
      p53, Ki-67 and c-erb B2 in 38 pituitary adenomas with immunohistochemical
      positivity for GH and prolactin (n=26; 68.4%), for prolactin (n=9; 23.7%) and for
      GH (n=3. 7.8%). The analyses revealed the following results: 24 (63.2%) tumors
      expressed variable positivity for c-erb B2, 11 (28.9%) expressed p53 positivity
      and 11 (28.9%) tumors were variably positive for Ki-67. Our results demonstrated
      a high percentage of GH/prolactin-, prolactin- and GH-secreting tumors with
      immunohistochemical positivity for c-erb B2. Once this membrane receptor is
      related to growth factors EGF and TGFalpha and both have a definite effect on
      tumor growth, our data suggest a possible role for c-erb B2 on the evolution of
      these tumors.

PMID- 16622556
TI  - [Immunohistochemistry in oligodendrogliomas].
AB  - Oligodendrogliomas (OL) are neuroepithelial tumors characterized by the presence
      of uniformly round nuclei with a clear cytoplasm around it. These features can
      also be seen in central neurocytomas, DNTs and clear cell ependymomas.
      Immunohistochemistry with glial and neuronal markers may be helpful in
      differential diagnosis. The aim of this study was to determine the glial and
      neuronal differentiation in 42 specimens of otherwise typical OL using
      immunohistochemical techniques. Ten cases showed anaplastic characteristics.
      Thirty-three samples (78.5%) were positive to GFAP with few cells stained in ten
      cases and many positive cells in six. Twelve cases (28.5%) were focally positive
      to NSE and/or synaptophysin showing neuronal differentiation. Thirty-four cases
      (80.9%) expressed S-100. In conclusion, glial proteins may be present focally in
      OL due to presence of mature reactive astrocytes or transitional forms between
      astrocytes and oligodendrocytes. Focal areas of neuronal differentiation can also
      be found in typical OL. The widespread staining with neuronal marker suggests
      central neurocytoma, but this diagnosis should not be done with small amount of
      tissue.

PMID- 16622557
TI  - [Size and proliferative index correlation in acoustic neuromas].
AB  - Acoustic neuromas are the most common tumors in the cerebellopontine angle. The
      molecular mechanisms involved in generation and growth of these tumors are not
      completely elucidated. Many radiological, clinic and immunohistochemistry data
      were correlated to tumor growth. We studied 11 acoustic neuromas surgically
      treated at Hospital Sao Paulo/Unifesp and correlated clinical and radiological
      data with proliferative index (Ki-67). The size of the tumors were positively
      correlationated with proliferative index. No other correlation had statistic
      significativity.

PMID- 16622558
TI  - [Olfactory groove meningioma: correlation between clinicoradiological features
      and proliferative index (Mib-1)].
AB  - OBJECTIVE: The aim of this study is to correlationate demographic, radiologic
      features and proliferative index defined by immunohistochemical expression of Mib
      1 in olfactory groove meningiomas, and to observe possible predictive factors of
      recurrence of this tumor. METHOD: There were analysed demographic, clinical and
      radiological features of 15 patients with olfactory groove meningioma. Fifteen
      paraffin-embebed tumors were studied by immunohistochemical methods for the
      expression of proliferative index by the Mib-1. RESULTS: There was a
      statistically positive correlation between tumoral and edema volumes. There was
      no correlation between Mib-1, tumoral volume, tumoral edema and frontal skull
      base abnormalities. Two cases with tumor recurrence had proliferative indices
      higher than the mean index. CONCLUSION: Larger tumors were more susceptible to
      develop peritumoral edema. The proliferative index has no positive correlation
      with tumoral volume, edema volumes and skull base invasion, but probably it is
      associated with tumoral recurrence.

PMID- 16622559
TI  - [Olfactory groove meningioma].
AB  - Olfactory groove meningiomas compromise approximately 8-18% of intracranial
      meningiomas and harbor frequently large sizes when diagnosticated. We report 13
      consecutive cases operated on Hospital Sao Paulo and Hospital Professor Edmundo
      Vasconcelos between 1995 and 2003. These patients were retrospectively studied
      regarding clinical preservation, surgical results and complications. The patients
      underwent uni or bifrontal craniotomies. There were nine complete resections
      including duramater and infiltrate bone and four patients with tumor removal and
      duramater coagulation. One patient died on post-operative period due to brain
      infarction and three patients had cerebrospinal fluid fistula that resolved.
      There were no symptomatic recurrence on the follow-up period of 3.3 years(range
      11 m to 8 years). With current microsurgical techniques, these tumors can be
      resected safely with low morbidity.

PMID- 16622560
TI  - [Epidemiological study of the traumatic brachial plexus injuries in adults].
AB  - OBJECTIVE: This study aims to provide information about epidemiological factors
      related to traumatic brachial plexus injuries in adults. METHOD: Prospective
      analysis of 35 consecutive cases, observed in a period of one year. RESULTS: Most
      of the lesions were supraclavicular (62%). Twenty-one cases occurred due to
      traction (60%), 9 to gun shot wound (25%), 3 to compression (8.5%) and two
      perforation/laceration (5.7%). Motorcycle accidents were the cause of trauma in
      54% of patients. CT myelography demonstrated root avulsion in 16 cases (76%).
      Partial spontaneous neurological recovery was observed in 43% of the patients.
      Neuropathic pain occurred in 25 (71%) cases, and the use of some oral intake
      drugs (as amitriptyline or carbamazepine) controlled it in 64% of times.
      CONCLUSION: Traction is the most frequent mechanism related to brachial plexus
      injuries, and root avulsions are common in this cases. Pain and concomitant
      lesions are frequently observed in these group. In this series, the rate of
      incidence to the local population was 1.75/100000/year.

PMID- 16622561
TI  - [Episodic tension-type headache: clinical evaluation of 50 patients].
AB  - A case series study of 50 consecutive patients with episodic tension type
      headache (ETTH) was conducted. Clinical aspects, family history and impact on
      work activities were studied. The casuistry was made up of 40 women and 10 men.
      The average age was 30 (+/-12) years. Constrictive pain was present in 40
      patients (80%). Sickness was the most commonly reported related phenomenon (20%).
      As expected, bilateral pain predominated; however, unilateral location was also
      present (10%). Although classically described as a mild pain, we observed that
      ETTH can come in intense crisis (16%). Family history of tension type headache
      was positive in 12 patients. The impact on work activities was substantial (14%).
      Our findings regarding to clinical aspects are in agreement with the literature.
      It is important to mention that the impact of ETTH on the individual and society
      should be reconsidered, and is more substantial than has been reported to date.

PMID- 16622562
TI  - [Transcranial Doppler in the neurological practice].
AB  - Transcranial Doppler (TCD) was described in 1982 by Rune Aaslid and introduced in
      Brazil in 1992 by Roberto Hirsh in the University of Sao Paulo. Since the
      acquisition of TCD by Neurology Division of Hospital de Clinicas of Universidade
      Federal do Parana (HC-UFPR) in 2001, the knowledge about TCD clinical utility has
      been increasing for diagnosis, follow-up and management of patients with
      cerebrovascular diseases. The objective of this study is to describe the current
      TCD indications and medical specialties indicators in our hospital. Although
      guidelines as published by the American Academy of Neurology establish values for
      TCD study with methods specificity and sensibility, we realize that the utility
      in our center depends on our efforts to show methods beneficial in various
      clinical settings.

PMID- 16622563
TI  - [Basal ganglia calcification on computed tomography: clinical characteristics in
      25 patients].
AB  - Twenty-five patients presenting basal ganglia calcification were assessed. This
      finding comprised 0.68% of all skull CT scan carried out during the period. Two
      patients were neurologically asymptomatic and 23 presented a variety neurological
      disorders--headache (7 patients), stroke (5 patients), extrapyramidal syndromes
      (2 patients), tumor (2 patients), epilepsy (1 patient), mental retardation (1
      patient), dementia (1 patient), cranial trauma (1 patient), other neurological
      conditions (3 patients)--or were asymptomatic from the neurological point of view
      (2 patients). Findings in the CT scan other than the basal ganglia calcification
      were observed in 15 (60%) patients. There was a clinical-CT scan correlation in
      these cases but not in those in which the basal ganglia calcification was an
      isolated finding. This study highlights the fact that basal ganglia calcification
      is often a nonspecific finding on CT scan and that it may not be possible to
      establish a clinical-pathological correlation between them.

PMID- 16622564
TI  - [Dichotic listening and spect in dyslexic children].
AB  - Dichotic listening (DL) was evaluated in 36 children with: verbal dichotic
      listening test, alternating disyllable dichotic test and non-verbal dichotic
      listening test. Children were separated into two groups: experimental group with
      18 dyslexic children and control group with 18 normal children. Both groups were
      comparable in gender, laterality and social-economic level. All dyslexic children
      underwent neuroimaging exam (SPECT). Our data showed that there was a statistical
      difference between both groups in all DL tests. Abnormal SPECT findings were seen
      in 50% of the dyslexic children, hypoperfusion of the left temporal lobe being
      the most frequent abnormality. We conclude that dyslexic children present an
      impairment of central neurologic processing that may be detected by DL tests, and
      by functional imaging exam, such as SPECT, as well.

PMID- 16622565
TI  - [Neuromodulatory effects of bromazepam when individuals were exposed to a motor
      learning task: quantitative electroencephalography (qEEG)].
AB  - The sedative effects of bromazepam on cognitive and performance have been widely
      investigated. A number of different approaches have assessed the influence of
      bromazepam when individuals are engaged to a motor task. In this context, the
      present study aimed to investigate electrophysiological changes when individuals
      were exposed to a typewriting task after taking 6 mg of bromazepam. qEEG data
      were simultaneously recorded during the task. In particular, relative power in
      delta band (0.5-3.5 Hz) was analyzed. Time of execution and errors during the
      task were registered as behavioral variables. The experimental group, bromazepam
      6 mg, showed a better motor performance and higher relative power than control
      individuals (placebo). These results suggest that the use of bromazepam reduces
      anxiety levels as expected and thus, produces an increment in motor performance.

PMID- 16622566
TI  - [Dropped head syndrome in motor neuron disease].
AB  - Dropped head is a syndrome caused by weakness of the neck extensor muscles found
      in different kinds of neuromuscular disorders and also in amyotrophic lateral
      sclerosis. This is a cases report of three women with motor neuron disease with
      beginning of dysphagia and cervical weakness that it evolved with dropped head.
      The investigation showed normal magnetic resonance imaging of brain and cervical
      column. Needle electromyography showed active and chronic denervation in bulbar
      muscles and cervical, thoracic and lumbosacral segments. We discuss the
      characteristic of disease, specially the clinical manifestations and
      electromyography features, with emphasis at the clinical evaluation of dropped
      head in the suspicion of motor neuron disease.

PMID- 16622567
TI  - Generalized periodic EEG activity in two cases of neurosyphilis.
AB  - Neurosyphilis is a recognized cause of epileptic seizures and cognitive
      impairment, but is not usually associated with the finding of generalized
      periodic activity in the EEG. We report two similar cases characterized by
      progressive cognitive impairment followed by partial complex seizures, in whom
      the EEG showed generalized periodic activity. Both cerebrospinal fluid and the
      response to penicillin therapy confirmed the diagnoses of neurosyphilis in the
      two cases. The finding of EEG generalized periodic activity in patients with
      cognitive or behavioral disorders is usually associated with Creutzfeldt-Jakob
      disease, although there are other conditions, some of them potentially
      reversible, which may also present this EEG abnormality. Neurosyphilis has tended
      not to be included among them, and our present findings support the importance of
      first ruling out neurosyphilis in those patients with cognitive or behavioral
      disorders associated with generalized periodic epileptiform discharges.

PMID- 16622568
TI  - Tuberculous meningoencephalomyelitis and coinfection with HTLV-I + HTLV-II: case
      report.
AB  - HTLV-I and HTLV-II are endemic in some areas of Brazil, where an associated
      disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) have
      been diagnosed in significant number of infected individuals. Tuberculosis has
      been demonstrated among those individuals, with higher prevalence than in the
      general population, suggesting that there is an increased risk for this
      comorbidity. We report the case of an individual coinfected with HTLV-I and HTLV
      II, suffering from an insidious meningoencephalomyelitis caused by Mycobacterium
      tuberculosis. The patient was a 44 years old man successfully treated with
      steroids and antituberculous drugs, improving clinically and turning to a
      negative PCR and to a normal blood-cerebrospinal fluid barrier.

PMID- 16622569
TI  - Vertebrobasilar dolichoectasia as a cause of trigeminal neuralgia: the role of
      microvascular decompression. Case report.
AB  - Our purpose is to report a case of trigeminal neuralgia caused by vertebrobasilar
      dolichoectasia treated with microvascular decompression. A 63-year-old man sought
      treatment for a recurrent lancinating left facial pain in V2 and V3 trigeminal
      territories. The computed tomography angiography revealed a mechanical
      compression of the left trigeminal nerve due to vertebrobasilar dolichoectasia.
      The patient was submitted to a left suboccipital craniotomy. Shredded Teflon was
      introduced in the conflicting neurovascular area, achieving a satisfactory
      decompression. The patients pain resolved immediately. Vertebrobasilar
      dolichoectasia is a rare cause of trigeminal neuralgia and a successful outcome
      can be achieved with microvascular decompression.

PMID- 16622570
TI  - Cerebellar glioblastoma multiforme in an adult.
AB  - Cerebellar glioblastoma multiforme (GBM) is a rare tumor. This is the third case
      published in Brazilian literature and, the last one has been described more than
      15 years ago. The aggressive behavior of GBM prompts for fast treatment, which
      can be hampered by the fact that the diagnosis of GBM requires a high degree of
      suspicion. We describe a case of GBM in a 46 years old man. In conjunction, we
      present a literature review including particular issues, clinical data, advances
      in imaging studies, pathological characteristics, treatment options and the
      behavior of such malignant tumor.

PMID- 16622571
TI  - Occipital bi-transtentorial/falcine approach for falcotentorial meningioma: case
      report.
AB  - Lesions located in the bilateral posterior incisural space are difficult to treat
      due to limited exposure. The classical approaches to this area are limited for
      lesions located bilaterally and especially when the lesion extends also below the
      tentorium as it may occur with meningiomas. Kawashima et al. reported, in
      anatomic studies, a new occipital transtentorial approach: the occipital bi
      transtentorial/falcine approach, to treat such lesions. We present a patient with
      a large falcotentorial meningioma, located bilaterally in the posterior incisural
      space. The occipital bi-transtentorial/falcine approach allowed an excellent
      surgical exposure and complete tumor removal with an excellent patient outcome.

PMID- 16622572
TI  - Seesaw nystagmus caused by giant pituitary adenoma: case report.
AB  - Giant pituitary adenomas are uncommonly large tumors, greater than 4 cm in size
      that can produces endocrine symptoms, visual loss and cranial nerve palsies. We
      report the rare occurrence of seesaw nystagmus as the presenting sign of giant
      pituitary adenoma. A 50-year-old man presented with headache associated with
      visual loss and seesaw nystagmus. Perimetry revealed bitemporal hemianopia and
      magnetic resonance imaging showed a giant pituitary adenoma. After surgery,
      nystagmus disappeared. Our case is relevant in understanding its pathogenesis
      since it documents seesaw nystagmus in a patient bitemporal hemianopia due to a
      large tumor but without mesencephalic compression.

PMID- 16622573
TI  - Severe hyponatremia and the syndrome of inappropriate secretion of antidiuretic
      hormone (SIADH) associated with fluoxetine: case report.
AB  - Hyponatremia is a significant complication of treatment with serotonin selective
      reuptake inhibitors (SSRI). We describe a case of a 53-year-old woman that was
      started on fluoxetine 20 mg/day for depression. Nine days later, the patient
      started with weakness, nausea, progressing to confusion, inappetence and vomit.
      Three hours later she became unresponsive and had a generalized seizure. She was
      brought to our emergency service. On admission, the patient was normovolemic,
      without focal motor deficits, but had mild generalized muscle rigidity and
      Babinski's sign bilaterally. Serum sodium was 105 mmol/L, serum osmolality, 220
      mmol/L, and urinary osmolality, 400 mmol/L. The other laboratory exams, chest X
      ray, cerebrospinal fluid and cranium tomography were normal. She was found to
      have fluoxetine-induced SIADH and it was discontinued. We started the
      hyponatremia correction and, in 5 days, the mental status of the patient
      gradually returned to a normal baseline, paralleling the resolution of her
      hyponatremia, without recurrence. Hyponatremia and SIADH should be considered if
      a patient experiences deterioration in his or her clinical condition while taking
      SSRI. The use of SSRI antidepressants should be remembered in the differential
      diagnosis of drug-induced hyponatremia.

PMID- 16622574
TI  - Hypersexuality following bilateral thalamic infarction: case report.
AB  - Hypersexuality is a rare but well recognized condition following brain injury. It
      has been described secondarily to dysfunction in the hypothalamus, the temporal
      and frontal lobes. We report a 63 year-old man that developed neuropsychological
      disturbances with hypersexuality as a prominent feature, disinhibition and
      moderate memory loss, hypersomnia and irritability after a bilateral paramedian
      thalamic infarction. A SPECT showed frontal hypoperfusion. We believe that these
      findings are expression of frontal-subcortical circuits dysfunction, particularly
      the orbitofrontal circuit, secondary to dorso medial thalamic infarction which
      probably plays a role in the determination of human sexual behavior. This case
      favors a thalamic modulation of frontal function.

PMID- 16622575
TI  - Intramedullary spinal cysticercosis simulating a conus medullaris tumor: case
      report.
AB  - Cysticercosis is an endemic condition in many developing countries. Although it
      is the most common parasitic disease of the central nervous system, cysticercal
      involvement of the spinal cord is rare. It may occur as intradural
      extramedullary, intramedullary, intramedullary associated with intradural
      extramedullary or as the vertebral presentation. We report the case of a 53-year
      old woman who presented with low back pain of acute onset and no other symptoms.
      Magnetic resonance imaging (MRI) showed an intramedullary cyst of the conus
      medullaris region which, at pathological examination, was diagnosed as a
      cysticercal cyst. She refused anticysticercal agents and steroids
      postoperatively. After an eight-year follow-up, the patient performs the
      activities of her daily living with no difficulties, and annual spinal MRIs show
      no residual signs of the disease. Clinical, pathophysiological, diagnostic and
      therapeutic aspects of spinal cord intramedullary cysticercosis are discussed.

PMID- 16622576
TI  - [Cerebral amyloid angiopathy presenting as a brain tumor: case report].
AB  - We describe the unusual case of a 45-year-old male patient harboring an
      intracranial mass due to cerebral amyloid angiopathy whose clinical and
      radiological features were those of a low grade glioma. Biopsy revealed cerebral
      amyloid angiopathy. The clinical, radiological and pathological findings are
      discussed as we review the available literature.

PMID- 16622577
TI  - [Posterior longitudinal ligament ossification: case report].
AB  - Posterior longitudinal ligament ossification of cervical spine is a rare
      condition among caucasians. A 42 years old japanese patient with progressive
      walking difficulty was diagnosed with this pathology by CT scan and MRI and
      treated surgically by an anterior approach with arthrodesis. Pathophysiology,
      racial prevalence, clinical picture, radiological characteristics and surgical
      approaches options are revised.

PMID- 16622579
TI  - Energy and protein intakes of acute stroke patients.
AB  - BACKGROUND: Although protein-energy malnutrition has been cited as a frequent
      complication following stroke, there is very little data describing nutritional
      intake among hospitalized patients. OBJECTIVE: To report: i) the level of protein
      and energy intake, ii) the adequacy of intake during the first 21 days of
      hospitalization and iii) to examine the differences in nutritional intake
      associated with diet type (regular texture, texture-modified and enteral
      feeding). DESIGN: Prospective observational study of an inception cohort. The
      energy and protein intakes of well-nourished patients with recent onset of first
      time stroke were assessed at admission to hospital and at days 7, 11, 14 and 21.
      Adequacy of energy intake at each of these intervals was expressed as a
      percentage (actual intake/energy requirement assessed by indirect calorimetry x
      100). Adequacy of protein intake was assessed in a similar manner, with 1 g/kg of
      actual or adjusted body weight used to estimate requirement. The nutritional
      intakes of patients receiving regular diets, dysphagia diets and enteral tube
      feedings were compared using one-way ANOVA. RESULTS: The average energy intakes
      of the entire study group ranged from 19.4-22.3 Kcals/kg/day over five
      observation points, representing 80.3-90.9% of measured requirements; protein
      intake and ranged from 0.81-0.90 g/kg day yielding adequacy of intake of 81-90%
      of requirement. There were significant differences in energy intakes and/or
      adequacy of intake of patients receiving different diet types at days 11, 14 and
      21 (p < 0.05) and differences in protein intake and/or adequacy of protein intake
      at all intervals except admission (p < 0.05). Patients receiving enteral tube
      feedings consumed more calories and protein compared to those patients on regular
      or dysphagia diets. CONCLUSIONS: On average, newly diagnosed, well-nourished,
      hospitalized patients consumed 80-91% of their both their energy and protein
      requirements, in the early post stroke period.

PMID- 16622580
TI  - Leptin resistance conferred by a combination of single nucleotide polymorphism
      and the adoption of a Western lifestyle in urban areas of Thailand.
AB  - OBJECTIVES: An increasing number of lifestyle disorders have emerged in response
      to the rapid urbanization that has occurred in Thailand. Recently, leptin
      resistance has been nominated as a possible marker for the onset of metabolic
      disorders in Asian countries. The research aimed to assess the relationship
      between leptin-resistance and environmental and/or genetic factors by comparing
      urban and rural inhabitants in Thailand. METHODS: A total of 212 age- and sex
      matched subjects from an urban area (Bangkok) and from rural areas (Sai Noi)
      participated in the study. Anthropometric measurements, blood biochemistry,
      single nucleotide polymorphism analyses, and interviews concerning lifestyles and
      dietary habits were conducted individually. Backward elimination multiple
      regression analyses and least trimmed sum of square methods were used to estimate
      the effects of possible factors. RESULTS: A transition of staple food from rice
      to bread (decreased rice intake; p < 0.01 and increased bread intake; p < 0.05)
      was significant in urban areas. Leptin levels were higher in urban groups, with a
      significant difference in women (p < 0.001 in women and p = 0.06 in men), but not
      in men. Predictors selected for leptin-resistance in women were genotypes of
      UCP2, PPARg2, bread intake, living area, and smoking habit (r = 0.510); in men,
      genotypes of UCP2 and UCP3p, smoking habit, and rice intake (r = 0.315).
      CONCLUSIONS: Urban women with del/del type of UCP2 exhibited significant leptin
      resistance. A combination of urbanization and UCP2 genotype were considered to be
      responsible.

PMID- 16622581
TI  - Induction of immunological tolerance by oral, but not intravenous and
      intraportal, administration of ovalbumin and the difference between young and old
      mice.
AB  - BACKGROUND: Induction of immunological tolerance is dependent on the route of
      antigenic administration, the dose of an antigen and the age of animals.
      OBJECTIVES: We investigated the effect of age on the tolerance induction in mice
      by administration of antigen through different routes and at different doses.
      DESIGN: Young and old BDF1 mice were orally, intraportally or intravenously
      administrated with a low or a high dose of ovalbumin (OVA). Then, delayed-type
      hypersensitivity (DTH) responses and serum anti-OVA antibody levels were assessed
      after systemic immunization of OVA with alum after appropriate intervals.
      RESULTS: In the young mice, oral administration of OVA suppressed DTH response
      and anti-OVA IgG1, IgG2b, IgM and IgE level in a dose-dependent manner. In the
      old mice, however, the suppression of IgG1 and IgE levels was induced by oral
      administration of a low dose of OVA, but no suppression by a high dose. On the
      other hand, intraportal or intravenous injection of OVA did not suppress DTH
      response and enhanced anti-OVA antibody levels in a dose-dependent manner in both
      young and old mice. Production of anti-OVA IgG2a antibody after systemic
      injection of OVA was detected in the mice, which had been treated with
      intraportal or intravenous injection of OVA, but not detected in the mice, which
      had been treated with oral administration of OVA. On the contrary, suppression of
      anti-OVA IgE antibody was observed only in the mice, which had been treated with
      oral administration of OVA. CONCLUSION: The oral administration of OVA, neither
      intravenous nor intraportal, induced immunological tolerance to OVA. An adequate
      dose of OVA for the tolerance induction and the suppression of antibody
      production are different between young and old mice. The suppression of IgE
      antibody was observed only by oral administration of OVA, much obviously in young
      mice than in the old. The results also indicated that the antigen processing in
      the liver did not play a major role in the induction of oral tolerance to OVA.

PMID- 16622582
TI  - Associations of health, dietary and job-related factors, and mental problems with
      cardiovascular diseases in aging.
AB  - BACKGROUND: While cardiovascular diseases are prevalent in aging population,
      associations between different factors and cardiovascular diseases are less
      studied or inconsistency still exists. AIM: To determine which factors measured
      at baseline predicted overall cardiovascular diseases and hypertension, and which
      factors were currently associated with these conditions. METHODS: Based on a
      sample of aging and retired food industry employees (N = 100, mean age 62 years)
      associations of health, dietary and job-related factors and mental problems with
      overall cardiovascular morbidity and hypertension were assessed with independent
      samples t-test, chi2 test and binary logistic regression analyses. Data were
      derived from health examinations and self-completed questionnaires in 1989 and
      2000. RESULTS: Added medical findings, related to cardiovascular diseases,
      appeared as predictor of overall cardiovascular morbidity, while elevated blood
      pressure together with high systolic and diastolic pressure, dyslipidemia and
      elevated blood pressure together, added medical findings, and inability to enjoy
      daily activities predicted hypertension. According to our analyses most
      significant current associations with overall cardiovascular morbidity were
      feeling of weakness, dyspnoea, hopelessness about the future, cardiac arrhythmia,
      chronic mental stress and lower HDL cholesterol, and with hypertension metabolic
      syndrome, lower HDL cholesterol, hopelessness about the future and muscular
      fatigue on exertion. CONCLUSIONS: Health factors were most important predictors
      of hypertension during a long-term period, while health factors together with
      mental problems had significant current associations with overall cardiovascular
      morbidity including hypertension.

PMID- 16622583
TI  - The effect of staff care practices on nursing home residents' preferences:
      implications for individualizing care.
AB  - PURPOSE: To examine the effect of staff care practices on nursing home residents'
      preferences for dining location. METHODS: A cross-sectional study was conducted
      with 304 long-stay residents in six skilled nursing homes. Research staff
      conducted direct observations during meals for two days and interviewed residents
      on the same two days about their preferences for dining location for each
      scheduled meal (breakfast, lunch and dinner). RESULTS: Staff care practices were
      significantly related to residents' preferences to eat in the dining room for all
      meals after adjusting for resident characteristics and nurse aide staffing level.
      For each unit increase in the proportion of residents taken to the dining room
      for meals by staff, residents' preferences to eat in the dining room also
      significantly increased by approximately three to four percent for each mealtime
      period. DISCUSSION: Staff care practices may influence residents' reported
      preferences for dining location. Daily care practices may be inappropriately
      justified by residents' preferences, which are shaped by their nursing home care
      experience and reduced expectations. In efforts to individualize resident care,
      nursing home staff should consider the influence of established care practices on
      residents' reported preferences for daily care.

PMID- 16622584
TI  - Repeated assessment of energy and nutrient intake in 52 nursing home residents.
AB  - Studies in Swedish nursing-home patients have shown a high prevalence of protein
      energy malnutrition. One potential cause for this may be low food intake.
      OBJECTIVE: To examine the intake of energy and nutrients in the residents of a
      nursing home; to investigate changes in dietary intake and body-weight over time
      and to analyze two-year-mortality. DESIGN: Explorative study. Five-day weighed
      assessment of food intake repeated three times during 1.5 years. Analysis of body
      composition at baseline and recording of body weight every third month. Analysis
      of two-year mortality. RESULTS: Fifty-two residents had three complete dietary
      assessments. Mean age 84 +/- 7 years, 79% were female. Mean body weight was
      stable at 61 kg. Mean energy intake at baseline was 1501 kcal/d (25 kcal/kg/d)
      and mean protein intake was 53 g/d (0.9 g/kg/d). Mean intake of vitamin D,
      vitamin E, folic acid, selenium and dietary fibre was less than 60% of
      recommended. At the second assessment intake of energy and many nutrients was
      higher than at baseline, but at the third assessment intake had decreased. There
      was no correlation between energy intake and body weight over time. Two-year
      mortality was 52%. Male gender and low body-weight constituted an increased risk
      of mortality. Comparing survivors and non-survivors showed that the mean body
      weight was 9 kg higher in the survivors throughout the study (p=0.02). This group
      had a relatively lower fat free mass and higher fat mass than the non-survivors.
      The difference in body composition was only seen in females, possibly due to the
      low number of males. The survivors had higher intakes of most nutrients but this
      reached significance only for a few of them. The non-survivors had significantly
      higher intakes of sucrose. CONCLUSION: Intake of energy and many nutrients was
      low in these nursing-home patients, and decreased further after one year, without
      any change in body weight. The significant positive relation between energy
      intake and body weight at group level disappeared when analyzing data at an
      individual level. Male gender and low body weight were associated with increased
      risk of mortality.

PMID- 16622585
TI  - Nutritional status in elderly people admitted to community residential homes:
      comparisons between two cohorts.
AB  - The aim was to describe nutritional status and socio-demographic and medical data
      in people who were newly admitted to community residential homes (cohort 2), and
      to compare the results with a previous study performed in the same municipality
      four years earlier (cohort 1). One hundred and twenty-seven people, 65 years of
      age, or older, newly admitted to residential homes in a municipality in the
      southern part of Sweden, were consecutively included. Nutritional status was
      assessed, using a combination of anthropometry and serum protein measurements and
      by Mini Nutritional Assessment (MNA). The results showed that 32% of the
      residents in cohort 2 were assessed as protein-energy malnourished (PEM),
      compared with 38% in cohort 1. Body mass index, psychological stress or acute
      disease, and reduced fluid intake were items in MNA which had power to predict
      PEM. Residents in cohort 2, diagnosed as having severe medical diseases,
      increased as well as residents with neuropsychological problems. Simultaneously,
      the number living in residential homes decreased, as compared to cohort 1. These
      differences indicate that the admission criteria have changed between cohorts 1
      and 2.

PMID- 16622586
TI  - Microarray comparative genomic hybridization (CGH)-based prenatal diagnosis for
      chromosome abnormalities using cell-free fetal DNA in amniotic fluid.
AB  - Cell-free fetal DNA (cffDNA) in the supernatant of amniotic fluid, which is
      usually discarded, can be used as a sample for prenatal diagnosis. For rapid
      prenatal diagnosis of frequent chromosome abnormalities, for example trisomies
      13, 18, and 21, and monosomy X, using cffDNA, we have developed a targeted
      microarray-based comparative genomic hybridization (CGH) panel on which BAC
      clones from chromosomes 13, 18, 21, X, and Y were spotted. Microarray-CGH
      analysis was performed for a total of 13 fetuses with congenital anomalies using
      cffDNA from their uncultured amniotic fluid. Microarray CGH with cffDNA led to
      successful molecular karyotyping for 12 of 13 fetuses within 5 days. Karyotypes
      of the 12 fetuses (one case of trisomy 13, two of trisomy 18, two of trisomy 21,
      one of monosomy X, and six of normal karyotype) were later confirmed by
      conventional chromosome analysis using cultured amniocytes. The one fetus whose
      molecular-karyotype was indicated as normal by microarray CGH actually had a
      balanced translocation, 45,XY,der(14;21)(q10;q10). The results indicated that
      microarray CGH with cffDNA is a useful rapid prenatal diagnostic method at late
      gestation for chromosome abnormalities with copy-number changes, especially when
      combined with conventional karyotyping of cultured amniocytes.

PMID- 16622587
TI  - Addressing the musculoskeletal components of fracture risk with calcium and
      vitamin D: a review of the evidence.
AB  - Osteoporotic fractures are an extremely common and serious health problem in the
      elderly. This article presents the rationale for calcium and vitamin D
      supplementation in the prevention and treatment of osteoporotic fractures and
      reviews the literature evidence on the efficacy of this strategy. Two
      musculoskeletal risk factors are implicated in osteoporotic fractures in the
      elderly: the loss of bone mass due to secondary hyperparathyroidism and the
      increased propensity to falls. Calcium and vitamin D reverse secondary
      hyperparathyroidism with resultant beneficial effects on bone mineral density
      (BMD). Additionally, calcium and vitamin D supplementation significantly improves
      body sway and lower extremity strength, reducing the risk of falls. The effects
      of combined calcium and vitamin D on parathyroid function and BMD provide a
      strong rationale for the use of this therapy in the prevention and treatment of
      osteoporosis and osteoporotic fractures. There is general agreement that, in
      patients with documented osteoporosis, calcium and vitamin D supplementation
      should be an integral component of the management strategy, along with
      antiresorptive or anabolic treatment. Frail elderly individuals constitute
      another major target population for calcium and vitamin D because evidence from
      randomized studies in institutionalized elderly subjects demonstrates that these
      supplements reduce osteoporotic fracture risk, particularly in the presence of
      dietary deficiencies. However, the results of trials in community-dwelling
      subjects have been equivocal. Within the primary-care setting, further research
      is required to establish appropriate target subgroups for calcium and vitamin D
      supplementation; overall, the data are consistent with a benefit individuals with
      insufficient calcium and/or vitamin D, although patients with documented
      osteoporosis will derive further benefit in terms of fracture prevention from the
      addition of an antiresorptive agent.

PMID- 16622588
TI  - Multivariate statistical analysis of metal concentrations in teeth of residents
      of Silesian region, southern Poland.
AB  - Concentrations of 11 metals (Cd, Cr, Cu, Fe, Mn, Pb, Zn, Na, K, Ca, and Mg) were
      assayed in the teeth of two populations of the Silesian region. The first group
      (n = 83) comprised the residents of Katowice-Szopienice, a town located in the
      center of the Upper Silesian industrial region, in close proximity to a Pb plant,
      whereas the other was a group of residents of the agricultural community Strumien
      (n = 44). The concentrations of all the trace metals were found to be higher in
      the teeth of Katowice-Szopienice residents. The methods of cluster analysis
      distinguished two clusters of metals in the teeth: essential (Ca, Na, Mg, Zn, and
      K) and trace (Cd, Mn, Cr, Cu, Fe, and Pb) elements. Euclidean distances reflected
      the differences in concentrations between the two groups. The results obtained
      were analyzed using principal component analysis. Four principal factors
      accounted for 68.1% of the total variance for Katowice-Szopienice residents and
      for 80.1% for Strumien residents. The first factor showed high contributions of
      Cu and Cr, elements present in humans as a result of diet, and also Mn for
      Katowice-Szopienice residents because of environmental contamination. The second
      factor was characterized by large Zn and Cd fractions and, for Katowice
      Szopienice residents, Pb and K as well. The diversified exposure of both
      populations was reflected by the differences in Euclidean distances and
      contribution of particular elements with respect of principal components.

PMID- 16622589
TI  - Input and fate of anthropogenic estrogens and gadolinium in surface water and
      sewage plants in the hydrological basin of Prague (Czech Republic).
AB  - The concentration of the estrogens 17beta-estradiol, estriol, estrone, 17alpha
      ethinylestradiol, mestranol and norethisterone and of the anthropogenic
      gadolinium (Gd(ant)) has been determined in the creeks and rivers, sewage
      treatment plants and water works of the city of Prague. The rapid degradation of
      estrogens in surface water allows the estrogen concentration gradient to be used
      as a very precise and sensitive guideline by which to pin-point sewage leaks into
      surface run-off water. The rather conservative behavior of Gd(ant) in surface and
      ground water documents in the present case the presence of sewage water in the
      surface water cycle.

PMID- 16622590
TI  - Reduction of availability of trace metals in urban soils using inorganic
      amendments.
AB  - Urban soils in medium- and large-sized cities generally have shown elevated
      contents of environmentally important trace metals (e.g. lead, copper, zinc).
      Such high concentrations in soils of green areas, mainly recreational areas, can
      be a source of potentially toxic elements and pose a risk for human health. Thus
      the availability of these contaminants is an essential control parameter, as it
      indicates potential plant uptake and their transfer to humans via inhalation of
      suspended dust, or direct ingestion (i.e. hand to mouth pathway), or consumption
      of contaminated foodstuff. Young children are the most sensitive segment of the
      population. Addition of amendments to the soil is a feasible technique to reduce
      the availability of trace metals. Accordingly, four urban soils of green areas of
      Seville (Spain), with relatively high lead contents and moderate copper and zinc
      contents, were amended in the laboratory with four inorganic materials [acid
      zeolite (AZ), sodium zeolite (SZ), Slovakite (SL), apatite (AP)], at two rates
      (1%, 5% w/w) and incubated for 1 year. Significant decreases in EDTA-extractable
      metal contents were observed in some of the treatments after adding the
      amendments even before the incubation begun, mainly for SL treatments. The
      amendment that produced the longest lasting immobilisation effect, compared to
      control treatments, was AZ at the higher rate. The effects of SZ and SL tended to
      decrease with time, while the AP effect was almost negligible after 3 months of
      ageing. This study confirms the feasibility of using certain inexpensive soil
      amendments to at least temporarily immobilise metals in urban soils for the
      purpose of protecting human health, especially that of young children.

PMID- 16622591
TI  - A comparative evaluation of quality of life and life satisfaction in patients
      with psoriatic and rheumatoid arthritis.
AB  - Both rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have a negative
      impact on patients' quality of life (QOL). The aim of this study was to compare
      QOL and life satisfaction in patients with RA and PsA. Forty patients with PsA,
      40 patients with RA, and 40 healthy control subjects were included in the study.
      Demographic data and clinical characteristics including age, sex, disease
      duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP),
      peripheral pain assessed by visual analog scale (VAS) and Larsen scores of hand X
      rays were recorded. Nottingham Health Profile (NHP) was used to evaluate QOL, and
      Life satisfaction index (LSI) was used to measure psychological well-being in
      both groups. The demographic data of the subjects were similar between the
      groups. The scores of all NHP subscales were significantly higher and the scores
      of LSI were significantly lower in PsA and RA patients than in control subjects.
      The inflammation markers including ESR, CRP, pain by VAS and Larsen scores were
      found to be significantly higher in RA patients. The scores of LSI were similar
      between the groups. Although the scores of physical domains of NHP (pain and
      physical disability) were statistically higher in RA patients (p<0.05), the
      scores of psychosocial subgroups of NHP were similar between RA and PsA patients
      (p>0.05). Both PsA and RA patients had disturbed QOL and decreased life
      satisfaction. In conclusion, peripheral joint damage, inflammation, and physical
      disability are significantly greater in RA but psychosocial reflection of QOL and
      life satisfaction are the same for both groups which can be explained by the
      additional impact of skin disease in patients with PsA.

PMID- 16622592
TI  - Spontaneous pneumomediastinum and dermatomyositis may be a not so rare
      association: report of a case and review of the literature.
AB  - One patient with dermatomyositis (DM) who developed spontaneous pneumomediastinum
      (SPnM) is described. A review of 15 previously reported cases shows that this is
      a complication of DM but not of polymyositis. It occurs in young patients with
      recent onset of disease characterized by cutaneous vasculopathy, and patients
      treated with immunosuppressive drugs have, in general, better outcomes. We
      suggest that the onset of SPnM in DM patients must alert to possible vasculitic
      activity and that immunosuppressive agents with progressive tapering of
      corticosteroids are part of the most reasonable approach in these cases.

PMID- 16622594
TI  - Transport of L-proline, L-proline-containing peptides and related drugs at
      mammalian epithelial cell membranes.
AB  - Membrane transport of L-proline has received considerable attention in basic and
      pharmaceutical research recently. Of the most recently cloned members of the
      solute carrier family, two are "proline transporters". The amino acid transporter
      PAT1, expressed in intestine, kidney, brain and other organs, mediates the uptake
      of proline and derivatives in a pH gradient-dependent manner. The Na(+)-dependent
      proline transporter SIT1, cloned in 2005, exhibits the properties of the long
      sought classical IMINO system. Proline-containing peptides are of interest for
      several reasons. Many biologically important peptide sequences contain highly
      conserved proline residues. Xaa-Pro peptides are very often resistant to
      enzymatic hydrolysis and display, in contrast to Pro-Xaa peptides, a high
      affinity to the H(+)/peptide cotransporter PEPT1 which is expressed in
      intestinal, renal, lung and biliary duct epithelial cells. Furthermore, several
      orally available drugs are recognized by PEPT1 as Xaa-Pro analogues due to their
      sterical resemblance to small peptides.

PMID- 16622593
TI  - Prion protein gene (PRNP) polymorphisms in Xinjiang local sheep breeds in China.
AB  - Amino acid polymorphisms of the prion protein (PrP) gene (PRNP), particularly
      those occurring at codons 136, 154, and 171 have a significant influence on
      scrapie pathogenesis in many sheep breeds. We isolated blood samples from 222
      sheep representing the eight main local sheep breeds in the Xinjiang Autonomous
      Region, the territory with the most abundant local sheep breeds in China, to
      identify the PRNP polymorphisms and to determine whether these breeds were at
      risk for developing scrapie. A new PRNP polymorphism encoding either glycine (G)
      or arginine (R) at codon 85 as well as eight previously reported polymorphisms at
      codons 101, 112, 127, 141, 146, 154, 171, and 189 in other sheep breeds were
      detected. Interestingly, the alanine (A)/V polymorphism at codon 136 was not
      observed in this study, all sheep being homozygous for A at this position. While
      the previously identified polymorphism of argine (R) or histidine (H) at codon
      154 was detected, the H polymorphism was rare (2.25%). Four polymorphisms at
      codon 171 encoding glutamine (Q), R, H, or lysine (K) were detected. The
      predominant ARQ allele occurred at a high frequency of 77.48%, suggesting an
      increased risk of scrapie in Xinjiang Autonomous Region.

PMID- 16622595
TI  - Solid-phase S-3CR generates N-substituted alpha-aminonitriles for the synthesis
      of alpha-phenyl-alpha-(1-piperazinyl) substituted amino acids.
AB  - Structurally diverse amino acids were prepared as versatile synthons for
      combinatorial chemistry. Using an optimized solid-phase synthesis by Strecker
      three-component-reaction (S-3CR), two different polymer linker constructs
      carrying piperazine were investigated. (a) Acrylate derived base-labile linker
      yielded alpha-aminonitriles with N-alkylated piperazines via Hofmann elimination
      after quarternisation with an alkyl halide. The crude product purities were in
      the range of 54-87%. (b) A urethane type linker yielded alpha-aminonitriles with
      the free piperazine nitrogen when cleaved with acid and the product purities were
      72-93%. The alpha-aminonitriles were easily converted to novel Nepsilon) - Fmoc
      protected alpha-amino acids with alpha-(1-piperazinyl) and alpha-phenyl
      substituents.

PMID- 16622596
TI  - Influence of pegylated interferon-alpha therapy on plasma levels of citrulline
      and arginine in melanoma patients.
AB  - The aim of this study was to evaluate the effect of pegylated interferon-alpha
      (PEG-IFN-alpha) on the plasma citrulline/arginine ratio, regarded as an index of
      nitric oxide (NO) synthesis, in patients with high-risk melanoma. Forty patients
      were randomly assigned to either PEG-IFN-alpha treatment (n = 22) or to
      observation only (control group, n = 18). The treatment group received 6 microg
      PEG-IFN-alpha/kg once a week during 8 weeks, followed by a maintenance dose of 3
      microg/kg/wk. Blood was collected at different time points, plasma concentrations
      of citrulline and arginine were measured and the ratio of citrulline/arginine was
      calculated. Patients treated with PEG-IFN-alpha showed a significant decrease in
      the concentrations of citrulline and in the citrulline/arginine ratio during the
      whole study period, both compared to baseline values and to the control group.
      The data suggest that therapy with PEG-IFN-alpha results in a marked decrease in
      the synthesis of NO in melanoma patients.

PMID- 16622597
TI  - A role for ethylene in low-oxygen signaling in rice roots.
AB  - Inhibitors of action and synthesis of ethylene (Ag(+), norbornadien, Co(2+)) were
      able to reduce the level of gamma-aminobutyric acid (Gaba) in rice roots during
      the development of an anaerobic environment. The inhibitory effect was reversed
      by the addition of the G protein activator 5'-guanylylimidodiphosphate. Gaba
      accumulation was modulated by the presence of CO(2) (inhibitor of ethylene action
      and synthesis) and stimulated by 2-chloroethylphosphonic acid (ethefon). These
      findings are consistent with a role of ethylene during a low-oxygen stress.

PMID- 16622598
TI  - Icilin evokes a dose- and time-dependent increase in glutamate within the dorsal
      striatum of rats.
AB  - Icilin, the peripheral cold channel agonist, activates TRPM8 and TRPA1, localized
      on dorsal root ganglia and trigeminal neurons in rats. Icilin precipitates
      immediate wet-dog shakes in this species, which are antagonized by centrally
      acting mu and kappa opioid agonists, implicating the central nervous system in
      the behavioral response. We studied the effect icilin has on glutamate levels in
      the dorsal striatum, a brain region involved in movement. Icilin (0.25, 0.5 and
      0.75 mg/kg, i.p.) elicited a dose- and time-dependent increase in glutamate
      within the striatum, indicative of icilin's neurochemical effect in rats.

PMID- 16622599
TI  - Amino acid analysis by hydrophilic interaction chromatography coupled on-line to
      electrospray ionization mass spectrometry.
AB  - Collagens form a common family of triple-helical proteins classified in 21 types.
      This unique structure is further stabilized by specific hydroxylation of distinct
      lysyl and prolyl residues forming 5-hydroxylysine and hydroxyproline (Hyp)
      isomers, mostly 4-trans and 3-trans-Hyp. The molecular distribution of the Hyp
      isomers among the different collagen types is still not well investigated, even
      though disturbances in the hydroxylation of collagens are likely to be involved
      in several diseases such as osteoporosis and autoimmune diseases. Here, a new
      approach to analyze underivatized amino acids by hydrophilic interaction
      chromatography (HILIC) coupled on-line to electrospray ionization mass
      spectrometry (ESI-MS) is reported. This method can separate all three studied Hyp
      isomers, Ile, and Leu, which are all isobaric, allowing a direct qualitative and
      quantitative analysis of collagen hydrolysates. The sensitivity and specificity
      was increased by a neutral loss scan based on the loss of formic acid (46 u).

PMID- 16622600
TI  - Strategies to improve plasma half life time of peptide and protein drugs.
AB  - Due to the obvious advantages of long-acting peptide and protein drugs,
      strategies to prolong plasma half life time of such compounds are highly on
      demand. Short plasma half life times are commonly due to fast renal clearance as
      well as to enzymatic degradation occurring during systemic circulation.
      Modifications of the peptide/protein can lead to prolonged plasma half life
      times. By shortening the overall amino acid amount of somatostatin and replacing
      L: -analogue amino acids with D: -amino acids, plasma half life time of the
      derivate octreotide was 1.5 hours in comparison to only few minutes of
      somatostatin. A PEG(2,40 K) conjugate of INF-alpha-2b exhibited a 330-fold
      prolonged plasma half life time compared to the native protein. It was the aim of
      this review to provide an overview of possible strategies to prolong plasma half
      life time such as modification of N- and C-terminus or PEGylation as well as
      methods to evaluate the effectiveness of drug modifications. Furthermore,
      fundamental data about most important proteolytic enzymes of human blood, liver
      and kidney as well as their cleavage specificity and inhibitors for them are
      provided in order to predict enzymatic cleavage of peptide and protein drugs
      during systemic circulation.

PMID- 16622601
TI  - Decreases in taurine levels induced by beta-alanine treatment did not affect the
      susceptibility of tissues to lipid peroxidation.
AB  - We aimed to investigate the effect of decreased taurine levels on endogenous and
      induced lipid peroxide levels in liver, brain, heart and erythrocytes as well as
      prooxidant and antioxidant balance in the liver of rats administered beta-alanine
      (3%, w/v) in drinking water for 1 month to decrease taurine levels of tissues.
      This treatment caused significant decreases in taurine levels of liver (86%),
      brain (36%) and heart (15%). We found that endogenous and ascorbic acid-, NADPH-
      and cumene hydroperoxide-induced malondialdehyde (MDA) levels did not change in
      the liver, brain and heart homogenates following beta-alanine treatment. Also,
      H(2)O(2)-induced MDA levels remained unchanged in erythrocytes. In addition, we
      did not observe any changes in levels of MDA, diene conjugates, glutathione,
      alpha-tocopherol, ascorbic acid and the activities of superoxide dismutase,
      glutathione peroxidase and glutathione transferase in the liver. According to
      this, buffering or sequestering capacity of tissues to exogenous stimuli was not
      influenced by reduced taurine levels in tissues of rats.

PMID- 16622602
TI  - Alterations of taurine in the brain of chronic kainic acid epilepsy model.
AB  - The aim of the study was to investigate the changes of taurine in the kainic acid
      (KA, 10 mg/kg, s.c.) chronic model of epilepsy, six months after KA application.
      The KA-rats used were divided into a group of animals showing weak behavioural
      response to KA (WDS, rare focal convulsion; rating scale <2 up to 3 h after KA
      injection) and a group of strong response to KA (WDS, seizures; rating >3 up to 3
      h after KA injection). The brain regions investigated were caudate nucleus,
      substantia nigra, septum, hippocampus, amygdala/piriform cortex, and frontal,
      parietal, temporal and occipital cortices. KA-rats with rating <2 developed
      spontaneous WDS which occurred chronically and six months after KA injection
      increased taurine levels were found in the hippocampus (125.4% of control). KA
      rats with rating >3 developed spontaneous recurrent seizures and six months after
      injection increased taurine levels were found in the caudate nucleus (162.5% of
      control) and hippocampus (126.6% of control), while reduced taurine levels were
      seen in the septum (78.2% of control). In summary, increased taurine levels in
      the hippocampus may involve processes for membrane stabilisation, thus favouring
      recovery after neuronal hyperactivity. The increased taurine levels in the
      caudate nucleus could be involved in the modulation of spontaneous recurrent
      seizure activity.

PMID- 16622603
TI  - Peptaibiomics: an advanced, rapid and selective analysis of
      peptaibiotics/peptaibols by SPE/LC-ES-MS.
AB  - "Proteomics" and "peptidomics" are used as technical terms to define the analysis
      and study of all proteins and peptides expressed in an organism or tissue. In
      analogy we propose the name peptaibiomics for the analysis of a group of fungal
      peptide antibiotics (peptaibiotics) containing the characteristic amino acid Aib
      (alpha-aminoisobutyric acid). In analogy to the peptidome the complete expression
      of peptaibiotics by fungal multienzyme complexes should be named the peptaibiome.
      Peptaibiotics are defined as peptides containing Aib and exerting a variety of
      bioactivities. They comprise the sub-groups of N-acetylated peptaibols,
      characterized also by a C-terminal amide-linked 2-amino alcohol, and
      lipopeptaibols having in place of an acetyl group a lipophilic fatty acid acyl
      group. Furthermore, lipoaminopeptides are also known with long-chain fatty acid
      on the N-termini, a lipoamino acid in position three and a strongly basic
      secondary or tertiary amine form a subgroup of mixed forms which could not be
      integrated in one of these three previously mentioned groups. Here we present a
      specific and rapid screening method on the peptaibiome applicable directly onto
      filamentous fungi cultured in a single Petri dish. The method comprises solid
      phase extraction (SPE) of peptaibiotics followed by on-line reversed-phase HPLC
      coupled to an ion trap electrospray tandem mass spectrometer (ES-MS). The
      presence of these peptides is indicated by characteristic mass differences of
      Deltam = 85.1 Da representing Aib-residues which can be observed in the b-series
      of acylium fragment ions resulting from ES-MS. Partial sequences can be deduced
      from the data and compared with structures compiled in electronic peptaibol data
      bases. The judgement is possible whether or not structures are novel, already
      known or related to known structures. Suitability of the method is demonstrated
      with the analysis of strains of Trichoderma and its teleomorph Hypocrea. New
      sequences of peptaibiotics are presented and those being related to established
      10- to 18-residue peptaibols trichovirin, trichogin and trichotoxin, which have
      been described in the literature.

PMID- 16622604
TI  - Mass-spectrometrical analysis of proteins encoded on chromosome 21 in human fetal
      brain.
AB  - Overexpression of chromosome 21 genes is directly or indirectly responsible for
      the Down syndrome phenotype. In order to analyse chromosome 21 gene products
      (Chr21Ps), we extracted proteins from fetal human brain cortex and applied an
      ultracentrifugal and chromatographic prefractionation principle followed by two
      dimensional gel electrophoresis (2-DE) and mass-spectrometrical analysis using
      high-throughput automated MALDI-TOF/TOF. Nine Chr21Ps were identified: pyridoxal
      kinase; superoxide dismutase [Cu/Zn] 1; carbonyl reductase 1; ES1 protein
      homolog, mitochondrial [Precursor]; cystathionine-beta-synthetase; T-complex
      protein 1, theta subunit; cystatin B; 6-phosphofructokinase; glycinamide
      ribonucleotide synthetase. Mass-spectrometric characterisation of Chr21Ps
      following separation in 2-DE gels is a useful tool for the analysis of these
      structures in brain, independent of antibody availability and specificity.

PMID- 16622605
TI  - Prediction of protein structural classes using support vector machines.
AB  - The support vector machine, a machine-learning method, is used to predict the
      four structural classes, i.e. mainly alpha, mainly beta, alpha-beta and fss, from
      the topology-level of CATH protein structure database. For the binary
      classification, any two structural classes which do not share any secondary
      structure such as alpha and beta elements could be classified with as high as 90%
      accuracy. The accuracy, however, will decrease to less than 70% if the structural
      classes to be classified contain structure elements in common. Our study also
      shows that the dimensions of feature space 20(2) = 400 (for dipeptide) and 20(3)
      = 8 000 (for tripeptide) give nearly the same prediction accuracy. Among these 4
      structural classes, multi-class classification gives an overall accuracy of about
      52%, indicating that the multi-class classification technique in support of
      vector machines may still need to be further improved in future investigation.

PMID- 16622606
TI  - Low doses of vanadate and Trigonella synergistically regulate Na+/K + -ATPase
      activity and GLUT4 translocation in alloxan-diabetic rats.
AB  - Oral administration of vanadate to diabetic animals have been shown to stabilize
      the glucose homeostasis and restore altered metabolic pathways. However, vanadate
      exerts these effects at relatively high doses with several toxic effects. Low
      doses of vanadate are relatively safe but unable to elicit any antidiabetic
      effects. The present study explored the prospect of using low doses of vanadate
      with Trigonella foenum graecum, seed powder (TSP), another antidiabetic agent,
      and to evaluate their antidiabetic effect in diabetic rats. Alloxan diabetic rats
      were treated with insulin, vanadate, TSP and low doses of vanadate with TSP for
      three weeks. The effect of these antidiabetic compounds was examined on general
      physiological parameters, Na(+)/K(+) ATPase activity, membrane lipid peroxidation
      and membrane fluidity in liver, kidney and heart tissues. Expression of glucose
      transporter (GLUT4) protein was also examined by immunoblotting method in
      experimental rat heart after three weeks of diabetes induction. Diabetic rats
      showed high blood glucose levels. Activity of Na(+)/K(+) ATPase decreased in
      diabetic liver and heart. However, kidney showed a significant increase in
      Na(+)/K(+) ATPase activity. Diabetic rats exhibited an increased level of lipid
      peroxidation and decreased membrane fluidity. GLUT4 distribution was also
      significantly lowered in heart of alloxan diabetic rats. Treatment of diabetic
      rats with insulin, TSP, vanadate and a combined therapy of lower dose of vanadate
      with TSP revived normoglycemia and restored the altered level of Na(+)/K(+)
      ATPase, lipid peroxidation and membrane fluidity and also induced the
      redistribution of GLUT4 transporter. TSP treatment alone is partially effective
      in restoring the above diabetes-induced alterations. Combined therapy of vanadate
      and TSP was the most effective in normalization of altered membrane linked
      functions and GLUT4 distribution without any harmful side effect.

PMID- 16622607
TI  - Poor outcomes after fibrinolytic therapy for ST-segment elevation myocardial
      infarction: impact of age (a meta-analysis of a decade of trials).
AB  - BACKGROUND: Fibrinolysis for ST-segment elevation myocardial infarction (STEMI)
      reduces mortality, but its relative efficacy and risks are age-dependent. We
      aimed to quantify the outcomes of fibrinolysis and adjunctive antithrombin
      therapy for STEMI stratified by age. METHODS: We performed a meta-analysis of 11
      published (1992-2001) randomized clinical trials of fibrinolysis in STEMI (sample
      size >or=3,000, no age limit, no placebo-controlled arms) identified by MEDLINE
      through June 2005. Event rates and odds ratios (OR) in elderly vs. younger
      patients were calculated for mortality, intracranial hemorrhage (ICH) and total
      stroke (CVA). Elderly patients were defined as >or=75 years (GUSTO I, TIMI 9B,
      GUSTO III, COBALT, ASSENT-2, InTIME-II TIMI-17, ASSENT-3, GUSTO V, and HERO-2),
      except when defined as >65 or >or=70 years by the study (INJECT and ISIS-3).
      RESULTS: Elderly (n = 24,531) vs. younger (n = 123,568) patients had increased
      rates of mortality (19.7% vs. 5.5%), ICH (1.4% vs. 0.5%) and CVA (3.5 vs. 1.2%)
      by 30-35 days; the excess risk for these events was substantial (OR mortality
      4.37, 95% CI 4.16-4.58; ICH 2.83, 2.47-3.24; CVA 2.92, 2.62-3.25; p < 0.001 for
      all). CONCLUSIONS: Despite established mortality reductions with fibrinolysis for
      STEMI, elderly compared with younger patients, still have a three to four fold
      increased risk of mortality and adverse events when treated with fibrinolysis and
      antithrombin therapy in the modern era. These robust estimates of the anticipated
      rates for mortality, ICH, and CVA can be used as benchmarks to monitor the
      efficacy and safety of therapies in ongoing and newly completed clinical trials.
      We aimed to quantify the outcomes of death, intracranial hemorrhage (ICH), and
      total cerebrovascular accidents (CVA) in elderly compared with younger patients
      treated with fibrinolysis for STEMI based on a meta-analysis of 11 randomized
      clinical trials (1992-2001) of more than 3,000 patients. Elderly (n = 24,531) vs.
      younger (n = 123 568) patients had increased rates of mortality, ICH and CVA by
      30-35 days; the excess risk was substantial (OR 4.37, 2.83, and 2.92
      respectively, p < 0.001 for all). These robust estimates can be used as
      benchmarks to monitor the efficacy and safety of therapies in ongoing and newly
      completed clinical trials.

PMID- 16622608
TI  - Risk factors of acute pulmonary thromboembolism in Japanese patients hospitalized
      for medical illness: results of a multicenter registry in the Japanese society of
      pulmonary embolism research.
AB  - BACKGROUND: Although the prophylaxis of acute pulmonary thromboembolism (APTE) in
      hospitalized patients has been improving in Japan, there is no report concerning
      APTE of Japanese medical patients. Therefore, the present study was designed to
      investigate the characteristics of APTE in Japanese patients hospitalized for
      medical illness, through a retrospective study. METHODS: In a total of 1,438
      registry patients with pulmonary thromboembolism for recent 10 years, 1,027
      patients with APTE were analyzed with respect to underlying diseases or
      predisposing factors, and clinical course. RESULTS: A hundred thirty three
      patients hospitalized for medical illness developed APTE, among 433 in-hospital
      APTE patients. The prevalence of APTE in women was more than in men. The mean age
      of the patients at diagnosis was 61 +/- 17 years. Main risk factors were a
      prolonged immobilization, stroke, cancer, indwelling central venous catheter.
      Fifty-four patients had 3 or more risk factors. In-hospital mortality rate was
      23%. CONCLUSIONS: Japanese patients in this registry had almost the same findings
      as in western patients, except for some points that had the possibility of
      demonstrating a difference between westerners and Japanese in the development of
      APTE. Our results will be available for establishing the prevention of APTE in
      medical patients in Japan.

PMID- 16622609
TI  - The use of a HEMOCHRON JR. HEMONOX point of care test in monitoring the
      anticoagulant effects of enoxaparin during interventional coronary procedures.
AB  - BACKGROUND: Enoxaparin is increasingly used for the anticoagulation of patients
      undergoing percutaneous coronary intervention (PCI). Several reports have
      suggested the utility of using point of care tests in monitoring the
      anticoagulation levels of enoxaparin in patients undergoing PCI. The objective of
      this study was to evaluate a new point-of-care test (POCT) HEMONOX in monitoring
      the anticoagulant effect of enoxaparin in non citrated fresh whole blood samples
      from patients undergoing elective PCI procedure. METHODS: Following IRB approval,
      blood samples were obtained from fifty-four patients who received two sequential
      intravenous doses of enoxaparin; 0.1 mg/kg followed 5 min later by 0.4 mg/kg for
      a total of 0.5 mg/kg. Blood was drawn at baseline and at 5, 10, 30 and 60 min
      post first bolus for evaluation in the clot-based POCT HEMONOX, ACT and aPTT and
      the chromogenic anti-Xa activity assay. RESULTS: HEMONOX clotting time (CT) at
      baseline was 62.6 +/- 6.2 secs, (n = 32) in healthy donors and statistically
      higher in PCI patients (71.6 +/- 9.1 secs, p = 0.0001). The peak HEMONOX response
      that was always achieved at 10 min post bolus was >100 secs in all 54 patients,
      of these 83% yielded CT >150 secs (range: 150-466). There was no detectable anti
      Xa activity level at baseline while peak HEMONOX CT corresponded to therapeutic
      levels (0.85 +/- 0.14 U/ml; range: 0.61-1.34). Both HEMONOX CT and anti-Xa level
      significantly decreased at the time of sheath removal. HEMONOX CT at peak
      response suggested 3 patient subgroups with different levels of sensitivity to
      enoxaparin: low, intermediate and high responders. The correlation between anti
      Xa activity level and HEMONOX CT was >or=0.85 in each patient subgroup when data
      from the 3 critical time points; baseline (absence of drug), peak response (10
      min post bolus) and sheath removal (60 min post bolus) were analyzed. The
      correlation diminished to >or=0.83 when the analyses included data from all 5
      time points [baseline, 5, 10, 30, and 60 min post bolus]. The HEMONOX test was
      the most sensitive POCT to measure the anticoagulant effects of enoxaparin. All
      patients completed PCI successfully. CONCLUSION: The HEMONOX test may be able to
      guide anticoagulation with enoxaparin during PCI. The HEMONOX assay is a one step
      whole blood coagulation test performed on the HEMOCHRON Jr. Signature + POC
      system. The method was evaluated to monitor the anticoagulant level of enoxaparin
      in blood samples from patients undergoing PCI after receiving an intravenous dose
      of 0.5 mg/kg. The results suggest a clear distinction of HEMONOX CT between the
      baseline value of untreated patients and patients achieving therapeutic
      enoxaparin levels.

PMID- 16622610
TI  - Is delayed facilitated percutaneous coronary intervention better than immediate
      in reperfused myocardial infarction? Six months follow up findings.
AB  - BACKGROUND: There are several new strategies proposed to improve the outcome of
      patients with ST-elevation myocardial infarction (STEMI). One approach is the
      resurgent use of facilitated percutaneous coronary interventions (PCI). Until
      recently, deciding whether immediate PCI after combined treatment (facilitated
      PCI) is more appropriate than delayed PCI (short time) has not been investigated.
      The aim of this study, therefore, was to investigate the outcomes in patients
      initially successfully treated pharmacologically and immediate PCI < 2 hr, and in
      patients initially successfully treated with pharmacological therapy and with
      delayed PCI (12-72 h). METHODS: 451 reperfused STEMI patients, aged 18 to 75
      years, class I-II Killip, with an acceptable echocardiographic window and
      admitted within 12 hs of the onset of symptoms were randomized into two groups.
      All patients had to have successful reperfusion, to receive the combination of a
      standard tirofiban infusion or abciximab plus half dose rtPA. Thereafter,
      patients were sub-grouped as follows:group 1 (immediate PCI) patients had PCI
      within 2 h; and group 2 (delayed PCI) patients in which PCI was performed after
      12 hs and within 72 hs. RESULTS: The 225 reperfused (immediate-PCI) and 226
      reperfused (delayed-PCI) patients (time from randomization to PCI 165 +/- 37 min
      in immediate PCI versus 45.1 +/- 20.2 h in delayed PCI group) showed similar
      results in ejection fraction, CK release and patency of the IRA. In addition, the
      delayed PCI group showed a significant reduction in ischemic events, restenosis
      and bleedings (P = 0.005, 0.01, 0.01 respectively) and significant reduced
      angiographic evidence of thrombus formation in the infarction-related artery
      (IRA) (p = 0.001). CONCLUSION: Our data suggest the safety and possible use of
      delayed facilitated PCI in patients with STEMI, and that delayed PCI in patients
      treated with combined lytic and IIb/IIIa inhibitors appears to be as effective
      and possibly superior (reduced ischemic events and repeat PCI) as immediate PCI.
      The patients in this study were successfully reperfused, with TIMI-3 flow and our
      data may not apply to patients with TIMI 0-2 flow. This strategy could allow
      transferring the reperfused patients and performing PCI after hours < 72 hours
      and not immediately, thereby reducing the number of urgent PCI and costs,
      obtaining similar results, but mostly causing less discomfort to the patient. Our
      results had to be interpreted with caution, because current guidelines do not
      recommend the combined therapy, but suggest further studies. The study was aimed
      to investigate the outcomes in patients initially successfully treated
      pharmacologically and immediate PCI < 2 h, and in patients initially successfully
      treated with pharmacological therapy and delayed PCI (12-72 h). All patients had
      to have successful reperfusion, to receive the combination of a standard
      abciximab or tirofiban infusion plus half dose rtPA. Similar results were
      observed in both groups. Delayed PCI group showed a significant lower incidence
      in restenosis (0.01), minor bleedings (0.005), ischemic events (0.01) and a
      reduced angiographic evidence of thrombus formation in IRA (0.001). Our data
      suggest the safety and possible use of delayed facilitated PCI in patients with
      STEMI. Our results had to be interpreted with caution, because current guidelines
      do not recommend the combined therapy, but suggest further studies.

PMID- 16622611
TI  - Doppler ultrasonography versus venography in the detection of deep vein
      thrombosis in patients with pulmonary embolism.
AB  - In patients with acute pulmonary embolism (PE) the frequency of deep vein
      thrombosis (DVT) varies between 13-93%. The aim of this study was to compare
      Doppler ultrasonography (DUSG) and venography in the detection of DVT in patients
      with PE. Fifty-one patients who were clinically diagnosed as having PE from
      January 1st 2001 to January 31st 2005 were entered into the study and comorbid
      conditions and risk factors were noted. The diagnosis of PE was confirmed by
      ventilation-perfusion (V/Q) scintigraphy, spiral tomography and angiotomography
      while the diagnosis of DVT was made by DUSG and venography. DVT was confirmed by
      both DUSG and venography in 19 (37,3%) patients. In the remaining 32 patients
      DUSG was negative. Venography confirmed DVT in 6 of these patients while in 26 no
      DVT was found. The sensitivity and specifity of DUSG in the diagnosis of DVT were
      76% and 100% respectively and the negative and positive predictive values were
      81% and 100% respectively. The mean d-dimer concentration was 1,187 in patients
      with DVT and 641 in patients without DVT (p > 0.05). Aquired risk factors were
      found in 4 of 6 patients with DVT, CRP was elevated in 5 (83%) and ALT-AST were
      elevated in 2 (33%). Although DUSG alone is considered sufficient for the
      diagnosis of DVT, venography still remains the gold standard in the diagnosis of
      DVT. Especially in patients with PE, where the diagnosis of DVT may increase the
      success of treatment, venography or other diagnostic tools may be used instead of
      a second DUSG if the first DUSG is negative.

PMID- 16622612
TI  - Does smoking status influence the effect of physical exercise on fibrinolytic
      function in healthy volunteers?
AB  - Exercise has been reported to simultaneously trigger and protect against sudden
      death, the so-called "The Paradox of Exercise". Differences in fibrinolytic
      function appear to exist between chronic and acute exercise. The aim of the
      present study was to assess the fibrinolytic system after strenuous exercise in
      healthy people and explored the influence of smoking habit. METHODS: 23 healthy
      male volunteers were studied (14 non-smokers; 9 current smokers). Citrated plasma
      blood samples were taken before and 30 minutes after a maximal exercise treadmill
      test, and levels of tissue type plasminogen activator (t-PA) antigen, plasminogen
      activator inhibitor (PAI-1) antigen and lipoprotein-a, Lp(a), [all ELISA] were
      measured as indices of fibrinolytic function. RESULTS: Smokers had higher body
      mass index and higher heart rate at baseline than non smokers (p = 0.046 and p =
      0.001, respectively). At baseline, smokers showed increased plasma Lp(a) levels
      than non smokers (p = 0.04), with no differences in t-PA and PAI-1 antigen
      levels. Following the exercise treadmill test, smokers had a shorter exercise
      duration and lower exercise capacity than non smokers (p = 0.008 and p = 0.004,
      respectively). This was associated with a reduction in t-PA antigen levels in the
      whole study population, (p = 0.048) without differences in PAI-1 levels, with no
      significant differences between smokers and non smokers. Lp(a) levels were also
      significantly reduced (p = 0.0001). CONCLUSIONS: Acute exercise alters plasma tPA
      antigen and Lp(a) levels, but there was no significant effect of smoking status
      in healthy subjects.

PMID- 16622613
TI  - Proinflammatory, immunomodulating, and prothrombotic properties of anemia and red
      blood cell transfusions.
AB  - For many years, the traditional treatment for hospitalized patients in the United
      States who have developed anemia, whether associated with medical illness,
      surgical procedures or trauma, has been red blood cell transfusion, despite the
      absence of supporting data in many patient populations. Emerging evidence
      suggests that transfusions may, in fact, be associated with risk beyond commonly
      held concerns of microbial transmission and acute antigen-antibody reactions. The
      following overview represents a biological paradigm for understanding the
      relationship between medical illness, surgical procedures, inflammatory states,
      anemia, red blood cell transfusion and immunothrombotic phenomena among
      hospitalized patients.

PMID- 16622614
TI  - Arterial and venous thrombosis in patients with von Willebrand's disease: a
      critical review of the literature.
AB  - All patients with von Willebrand's disease (vWD) who showed an arterial or venous
      thrombosis and were reported in the literature have been evaluated. 11 patients
      had arterial thrombosis while 19 had venous thrombosis for a total of 30 cases. 9
      out the 11 cases with arterial thrombosis had myocardial infarction. Two had
      cerebral thrombosis. Associated risk factors for arterial thrombosis were
      available only for three patients who showed, respectively, smoking and
      dyslipidemia (2 cases) and smoking and intravenous desmopressin infusion (1
      case). The majority of patients with venous thrombosis showed DVT with or without
      PE. Four patients presented with apparently isolated PE. In two instances
      thrombosis occurred in unusual sites (central retinal vein and portal vein,
      respectively). Several associated risk factors were present, mainly: infusion of
      FVIII or FVIII + vWF concentrates in 7 cases; surgery in 8 cases, pregnancy in 1,
      desmopressin infusion in 1, variable coagulation defects or polymorphisms in 5.
      More than one of these associated conditions were present in a few patients. The
      majority of vWD patients who showed thrombotic phenomena were type I patient, but
      in 6 cases were also type 3. The type of defect was not reported in 6 patients.
      As a conclusion of this review it seems safe to assume that both arterial and
      venous thrombosis appear rare in vWD. This is confirmed by the fact that arterial
      or venous thrombosis appears slightly more frequent in hemophilia A and B.

PMID- 16622615
TI  - Massive pulmonary embolism in a Lebanese patient doubly heterozygous for MTHFR
      and Factor V Leiden presenting with syncope and treated with tenecteplase.

PMID- 16622616
TI  - Thrombolysis as first choice therapy in prosthetic heart valve thrombosis. A
      study of 68 patients.
AB  - BACKGROUND AND OBJECTIVES: Valvular thrombosis is a serious complication in
      patients with prosthetic heart valves. Traditional treatment is emergency
      surgery, but thrombolysis provides a non invasive alternative. In this paper we
      evaluate the efficacy and safety of thrombolysis in prosthetic heart valve
      thrombosis. METHODS: Data of 68 patients diagnosed of prosthetic valve
      thrombosis, treated at the Institute of Cardiology and Cardiovascular Surgery,
      Havana during a 6-years period were analyzed. They received thrombolysis with a
      recombinant streptokinase infusion at 250,000 IU in 30 minutes followed by
      100,000 IU/hour during 72 hours or less if the thrombosis resolved before. The
      evaluation was based on clinical and echocardiographic findings. RESULTS:
      Affected sites were mitral (50 cases), tricuspid (9), and aortic (9). Mean time
      of prosthesis implantation was 6.8 years. The presentation form was generally
      heart failure (NYHA functional class III-IV) in 64 (94.1%) patients. Mean time
      interval between onset of symptoms and diagnosis was 10.6 days. There was total
      response to treatment in 58 (85.3%) patients, partial in 4 (5.9%) and failure in
      6 (8.8%). Recombinant streptokinase overall dose was 5.1 x 10(6) IU and mean
      infusion time 50 hours. Major hemorrhagic complications were observed in two
      patients. Five embolic events occurred during thrombolysis. Four patients died.
      Rethrombosis was noted in 11 patients; 10 were retreated successfully with
      thrombolysis. CONCLUSIONS: Thrombolysis with recombinant streptokinase is
      efficacious and safe for the treatment of prosthetic heart valve thrombosis. It
      does not contraindicate surgical treatment if there is no total response, because
      patient goes to surgery in better hemodynamic conditions with lower risk.
      Nowadays it can be considered as first-line treatment in all patients with
      prosthetic heart valve thrombosis regardless of functional class unless specific
      contraindications exist.

PMID- 16622617
TI  - Monitoring anticoagulation in atrial fibrillation.
AB  - BACKGROUND: Randomized control trials and observational studies show high-quality
      warfarin therapy leads to safe and effective stroke prophylaxis. In usual
      community practice, patient, physician and health care system factors are
      barriers to optimal anticoagulation. We examined the predictive relationship
      between inpatient and outpatient INR values in chronic non-valvular atrial
      fibrillation (AF) patients hospitalized for ischemic stroke (S), bleed (B) and
      control events (C) in usual community practice. METHODS: This nested case-control
      analysis identified AF patients hospitalized for S, B and C using medical and
      pharmacy claims spanning 4.5 years ('98-'03) and validating diagnosis with chart
      abstraction. AF was defined as 2 medical claims for AF >or= 42 days apart with a
      related prescription claim for warfarin. INRs from both outpatient and inpatient
      settings were used to yield a continuous history of coagulation status. Time-in
      therapeutic-range (TTR) was calculated by Rosendaal's linear interpolation
      method. Correlation of inpatient and prognostic utility of last outpatient INRs
      was tested with S or B hospitalizations using univariate and multivariate
      logistic regression. RESULTS: Overall, 614 hospitalizations (means: age 73.9,
      CHADS(2) = 3.24; 52% male) included S (n = 98), B (n = 101) and C (n = 415)
      events. Average TTR was 28.6% (49.4% at INR <2.0, 21.9% at INR >3.0). First INR
      on admission (INR <2.0 or >3.0) was associated with S and B hospitalizations (OR
      adjusted [95%CI], 1.68 [1.04-2.73] and 1.72 [1.02-2.90]), respectively. Last
      outpatient INR <2.0 was not associated with S (OR-adjusted [95%CI], 1.12 [0.77
      1.81]), and INR >3.0 was not associated with B (OR-adjusted [95%CI], 1.25 [0.67
      2.32]). Last outpatient INR measurement occurred at 28, 22 and 24 days (median;
      S, B & C, respectively) before hospitalization. CONCLUSION: Patients were
      observed within therapeutic range less than 30% of their time on warfarin. While
      inpatient INRs were clearly associated with both ischemic stroke and bleed
      events, last outpatient INR before event was not predictive.

PMID- 16622618
TI  - Association between plasma levels of D-dimer and fibrinogen/fibrin degradation
      products (FDP) for exclusion of thromboembolic disorders.
AB  - BACKGROUND: D-dimer and fibrinogen/fibrin degradation products (FDP) levels are
      elevated in subjects with thromboembolic disorders, and the assays for detection
      of D-dimer and FDP are used in many laboratories for the investigation of these
      disorders. The aim of this study was to evaluate the association between the
      plasma levels of D-dimer and FDP in the investigation of thromboembolic
      disorders. METHODS: D-dimer and FDP immunoassays were performed in 217
      consecutive blood samples from subjects with suspected of thromboembolic
      disorders by use of Liatest D-dimer and Plasma FDP. RESULTS: FDP results were
      classified in: <5, 5-20, >20 microg/mL, and D-dimer levels obtained in these
      groups ranged to 350-1,210 ng/mL, 420-1,960 ng/mL, and 1,190-51,170 ng/mL,
      respectively. A significant association between D-dimer levels and the reaction
      times necessary to occur agglutination in latex agglutination test for FDP was
      observed. CONCLUSIONS: There was an association between plasma levels of D-dimer
      and FDP. The preliminary determination of FDP levels could be useful because it
      allows estimating the D-dimer levels before of the automated systems analysis,
      reducing costs associated to dilutions of plasma samples.

PMID- 16622619
TI  - Preoteomics, metabolomics and circulating endothelial progenitor cells in acute
      coronary syndromes.

PMID- 16622620
TI  - Once more confirmed: adjuvant radiotherapy and improved local control provide a
      significant survival benefit for early breast cancer patients.

PMID- 16622621
TI  - [Role of radiation therapy on the use of primary ("neoadjuvant") systemic
      treatment of breast cancer].
AB  - BACKGROUND: The indications for primary ("neoadjuvant") systemic treatment (PST)
      for breast cancer have evolved over the last few years. PST is not only used in
      patients with locally advanced breast cancer (LABC) and inoperable tumors but
      also plays a role for operable tumors aiming at breast conservation and higher
      complete remission rates (ypCR). The contribution of radiotherapy and the optimal
      sequencing of chemotherapy, surgery and radiotherapy still have to be defined.
      MATERIAL AND METHODS: Objectives and results of PST for inflammatory, locally
      advanced and operable breast cancer were analyzed according to tumor stage.
      RESULTS: Radiotherapy following PST and surgery is the standard of care for
      inflammatory breast cancer, LABC and nonresectable lesions. Comparable results
      are achieved for good responders after PST receiving radiotherapy or surgery. The
      evaluation of a preoperative radiotherapeutic approach is complicated by
      different chemo- and radiotherapy regimens, continuation of chemotherapy after
      surgery and heterogeneous patient groups. CONCLUSION: For LABC and inflammatory
      breast cancer the role of PST is well defined. For operable lesions, however, the
      value of preoperative radiotherapy still has to be established. This should be
      assessed within the framework of a clinical trial using standardized parameters
      for applying chemotherapy as well as radiation therapy.

PMID- 16622622
TI  - Maintenance chemotherapy after chemoradiation improves survival of patients with
      locally advanced pancreatic carcinoma: a retrospective analysis of prospectively
      recruited patients.
AB  - BACKGROUND AND PURPOSE: Currently, there is no treatment standard for patients
      with locally advanced pancreatic cancer (PaCa) after chemoradiation. The aim of
      the present study was to retrospectively assess overall survival and toxicity of
      chemotherapy in addition to chemoradiation in this patient group. PATIENTS AND
      METHODS: Three-dimensional conformal irradiation to the primary tumor (55.8 Gy)
      and the lymphatics (50.4 Gy) was combined with 5-fluorouracil- or gemcitabine
      based chemotherapy followed by additional chemotherapy with gemcitabine until
      progression or no further treatment. Decision for chemotherapy was taken at the
      discretion of the attending physician considering the patient's desire. RESULTS:
      A total of 172 patients were addressed to the local tumor board. Patients with
      (neo)adjuvant treatment or metastatic disease were excluded (n = 90). 82 patients
      were treated with chemoradiation and had additional chemotherapy (n = 40) or no
      further treatment (n = 42). Characteristics of the two groups were equally
      distributed. Patients with chemotherapy had significantly longer overall survival
      as compared to patients without (13 months vs. 8 months; p < 0.0001; median
      survival = 10.7 months for all patients). Acute toxicity of maintenance
      chemotherapy was relatively mild. CONCLUSION: Maintenance chemotherapy after
      chemoradiation for patients with locally advanced PaCa may significantly increase
      survival rates without severe side effects and is therefore recommended as
      standard treatment following chemoradiation.

PMID- 16622623
TI  - Frameless stereotactic radiosurgery of a solitary liver metastasis using active
      breathing control and stereotactic ultrasound.
AB  - BACKGROUND AND PURPOSE: Radiosurgery of liver metastases is effective but a
      technical challenge due to respiration-induced movement. The authors report on
      the initial experience of the combination of active breathing control (ABC) with
      stereotactic ultrasound (B-mode acquisition and targeting [BAT]) for frameless
      radiosurgery. PATIENTS AND METHODS: A patient with a solitary, inoperable liver
      metastasis from cholangiocellular carcinoma is presented (Figure 4). ABC (Figure
      3) was used for tumor/liver immobilization. Tumor/liver position was controlled
      and corrected using ultrasound (BAT; Figure 1). The tumor was irradiated with a
      single dose of 24 Gy. RESULTS: Using ABC, the motion of the tumor was
      significantly reduced and the overall positioning error was < 5 mm (Figure 2).
      BAT allowed a rapid localization of the lesion during breath hold which could be
      performed without difficulties for 20 s. Overall treatment time was acceptable
      (30 min). CONCLUSION: Frameless stereotactic radiotherapy with the combination of
      ABC and BAT allows the delivery of high single doses to targets accessible to
      ultrasound with high precision comparable to a frame-based approach.

PMID- 16622624
TI  - Total-body irradiation--role and indications: results from the German Registry
      for Stem Cell Transplantation (DRST).
AB  - BACKGROUND AND PURPOSE: Total-body irradiation (TBI) is a key part of the
      conditioning regimen before hematopoietic stem cell transplantation (HSCT). The
      exact role of TBI as part of the conditioning regimen is largely unclear. In
      order to determine the relevance of TBI, the status of TBI utilization was
      analyzed on the basis of a nationwide registry. MATERIAL AND METHODS: 14,371
      patients (1998-2002) documented in the German Stem Cell Transplantation Registry
      (DRST) were analyzed regarding TBI utilization prior to autologous or allogeneic
      transplantation, underlying disorder, type of donor, stem cell source, and size
      of the treatment center. RESULTS: For autologous HSCT approximately 10% of the
      patients (873/8,167) received TBI, with chronic lymphocytic leukemia (CLL,
      approximately 80%, 171/214) and low-grade non-Hodgkin's lymphoma (l-NHL,
      approximately 35%, 330/929) being the most important disorders. In the allogeneic
      setting 50% of the patients (2,399/4,904) received TBI, with acute lymphocytic
      leukemia (ALL, 85%, 794/930), acute myeloid leukemia (AML, 45%, 662/1,487) and
      chronic myeloid leukemia (CML, 49%, 561/1,156) being the key indications. The
      type of donor, stem cell source and center size did not strongly influence the
      use of TBI. CONCLUSION: TBI has only a limited role for the conditioning prior to
      autologous HCST. For allogeneic HSCT TBI is widely accepted with no major changes
      over the observation time. The use of TBI is generally accepted for ALL, whereas
      approximately half of the patients with CML or AML received TBI. Although a
      considerably large database was analyzed, no clear determinants for the use of
      TBI could be distinguished.

PMID- 16622625
TI  - [Evaluation of the toxicity of tirapazamine plus cisplatin in a mouse tumor
      model].
AB  - BACKGROUND AND PURPOSE: Tirapazamine (TPZ) is an anticancer drug that is
      selectively activated by the low oxygen environment in solid tumors. Furthermore,
      TPZ also enhances the tumor cell-killing effect of cisplatin. So far, detailed
      information on the toxicity of combined treatment is rare. The authors evaluated
      the toxicity of TPZ in combination with cisplatin in a mouse tumor model. For
      this purpose, general toxicity was monitored and all inner organs were examined
      histologically. MATERIAL AND METHODS: RIF-1 fibrosarcomas of murine origin
      growing in the right hindfoot dorsum of C3H mice were used. The animals were
      treated with 10 x 2 Gy irradiation plus six i.p. injections of 4 mg/kg cisplatin
      (total dose 24 mg/kg) together with varying doses of TPZ (0-28 mg/kg per
      injection; total dose 0, 43.2, 86.4, 129.6, 151.2, 172.8 mg/kg). Treatment was
      applied within 2 weeks (Figure 1). Total observation period was up to 35 days.
      RESULTS: Combined treatment with TPZ led to a dose-dependent, significant
      decrease in motor activity (Table 1) and body weight and an increase in mortality
      (Figures 2 and 3, Tables 2 and 3). Histological analyses showed areas of necrosis
      in the heart, liver and kidney and gastric ulcers (Table 4). Cisplatin alone
      produced no severe toxicity. Tumor doubling times were TPZ dose-dependent and
      comparable with data from the literature (Figures 4 and 5, Table 3). CONCLUSION:
      Unlike most data from the literature a dose-dependent increase in toxicity was
      seen when adding TPZ to a standard treatment of cisplatin plus irradiation. To
      the authors' knowledge this is the first study histologically examining in detail
      the organ toxicity of TPZ in a mouse model. Furthermore, they expand the rare
      data on long-term toxicity after TPZ plus cisplatin in a fractionated therapy
      regimen. The results question the usefulness of frequently performed therapeutic
      studies where only short-term treatment and observation endpoints are used, since
      essential toxicities are likely to be overlooked.

PMID- 16622626
TI  - Evaluation of possible prostate displacement induced by pressure applied during
      transabdominal ultrasound image acquisition.
AB  - BACKGROUND AND PURPOSE: For accurate positioning of the prostate in external
      radiotherapy, transabdominal ultrasound localization and positioning systems are
      available. Reports have stated that probe pressure applied during image
      acquisition causes clinically relevant prostate displacement. The aim of this
      study was to investigate the prostate displacement due to the pressure applied
      during transabdominal ultrasound image acquisition with the BAT ultrasound
      system. MATERIAL AND METHODS: For ten patients who had undergone iodine-125 seed
      implantation for brachytherapy of prostate cancer, X-ray simulations were
      performed before and during ultrasound image acquisition. The iodine seeds are
      visible on the X-ray images, representing the position of the prostate. The
      simulator's crosshair, indicating the isocenter, was used as reference coordinate
      system. For each patient the change in prostate position was calculated based on
      the seed positions during and after ultrasound examination. RESULTS: A maximum
      displacement of the prostate of 2.3 mm in anteroposterior and 1.9 mm in
      craniocaudal direction and a rotational change of up to 2.5 degrees were
      observed. If the system was not handled correctly and too much pressure was
      applied, a shift of the prostate of up to 10 mm could be induced. CONCLUSION:
      Compared to the prostate displacement due to changes in rectal filling, which
      according to Crook et al. can be as much as 1.7 cm, the maximum displacement of
      less than 0.3 cm caused by the probe pressure is negligible. However, proper
      education of the staff and preparation of the patient are essential for the safe
      use of the system.

PMID- 16622627
TI  - Pigmented villonodular synovitis of the distal radioulnar joint.
AB  - CASE REPORT: A 32-year-old female patient underwent surgical synovectomy in the
      right distal radioulnar joint because of local recurrence of pigmented
      villonodular synovitis (PVNS) after previous surgery. 7 weeks after her second
      surgery she received fractionated radiation therapy (RT) to a total dose of 36.0
      Gy given in five weekly fractions of 2.0 Gy. Apart from a mild skin erythema the
      patient had no early morbidity related to the use of RT. After a follow-up of 36
      months no local recurrence was detected. CONCLUSION: In accordance with
      literature data the hitherto course of the presented case corroborates that RT is
      a safe and effective treatment option for the prevention of PVNS recurrence.

PMID- 16622629
TI  - [Active ageing and quality of life--Results of a WHO demonstration project].
AB  - Based on the Active Ageing Programme of the World Health Organization (WHO), a
      demonstration project was conducted in a city in North-Rhine Westphalia between
      October 2002 and December 2004. The aim of the study was to promote an active
      ageing process, to maintain autonomy and independence among older people, and
      thereby to promote health and quality of life. The target group included people
      aged 55 to 80 years. The aim was to include older persons in a critical period of
      life due to loss of partner within the last five years and people undergoing a
      status change due to retirement within the last two years. 344 participants were
      visited at home to assess their health and psychosocial situation and to identify
      opportunities for activities. Participants were supported in their efforts to
      realise the agreed-upon activities. In this article results of the external
      evaluation are presented. It is analysed whether quality of life according to the
      WHOQOL Bref improves among participants in the course of the project. Results of
      non-parametric tests show small differences in quality of life between the three
      waves of interviews (at the beginning of the project, after one year, at the end
      of the project). This holds true when only those participants are analysed who
      retired within the last two years. However, quality of life significantly
      improves among older persons who lost their partner within the last five years.
      In terms of implementation of the WHO Active Ageing Programme results suggest
      application of a risk group strategy.

PMID- 16622630
TI  - [On the stability and modifiability of the sense of coherence in active seniors].
AB  - According to Antonovsky, the sense of coherence (SOC) determines health and
      wellbeing. This life orientation is shaped up to the age of 30 and is supposed to
      remain constant up to senior age. In a field study, in which the SOC, psycho
      social resources and subjective health were assessed at three points in time, it
      could be shown for the first time that the SOC in old age can be malleable and
      expanding. The master sample (time t(1)) consisted of N = 58 active and "healthy"
      seniors at the mean age of 66.3 years (65.5% female), who decided to take part in
      a 14-week program focusing on physical activity and/or self-reflection (endurance
      training, strength training, yoga, or meditation), respectively. One year before,
      90% of them had participated in the Greifswald Aging Study (t0). The intervention
      study was attended regularly by n = 42 persons (t1 and t2). The SOC and
      associated health appraisals remained constant over a period of one year (t0-t1);
      re-test reliabilities varied from satisfactory to very good. Overall, the current
      SOC (t1) was more important than the past SOC (t0) in accounting for current well
      being (t1). The intervention (t1-t2) revealed that the elderly's SOC was
      significantly strengthened-independently of the program they took part in.
      Correspondingly, participants' wellbeing, subjective health and psycho-social
      resources were enhanced. Taking part in a systematic, age-based and group
      oriented program that encourages an active and productive every-day life brings
      about coherence-promoting and health-promoting life experiences in old age.

PMID- 16622631
TI  - [Persons requiring long-term care: Recommendation and utilization of
      rehabilitative therapies].
AB  - In Germany all members of the statutory health insurance are also compulsory
      members of the nursing care insurance which financially supports nursing care at
      home and in nursing homes. Benefits are provided dependent on a standardized
      medical examination performed at the home of the applicants by trained physicians
      or nurses of the health insurances' medical service (MDK). The benefits are
      granted to those persons who are limited in the performance of activities of
      daily living due to physical, cognitive or mental disorders. In the German Code
      of Social Law regulating the long-term care system, one important entitlement is
      "rehabilitation before long-term care". It aims at maintaining life of disabled
      persons in their familiar surroundings as long as possible. Up to now in the
      nursing care insurance this aim has been implemented insufficiently. The
      objective of this study was therefore to investigate the frequency of suggested
      ambulatory rehabilitation, which is recommended by the MDK at the examinations,
      and the following prescription of ambulatory rehabilitation, issued by an office
      based physician. The database included the medical examinations of the years 2001
      to 2002 linked to a random sample of persons insured in a statutory sickness fund
      in the German federal state of Hesse. Nursing care-related information including
      recommended rehabilitation therapy was derived from the medical examinations.
      Insurance data provided information on prescriptions. Data of 7,840 persons could
      be analyzed. Rehabilitative therapy was recommended in 15% of the nursing care
      applicants, mostly physiotherapy (ca. 90%). Persons receiving the recommendation
      were mainly male, they were younger, were more disabled, had less often a
      diagnosis of the ICD-10 chapter "symptoms and abnormal clinical and laboratory
      findings" or "mental and behavioral disorders", live less often alone and were
      more restricted in their motion compared to persons without recommendation for
      rehabilitative therapy. Only 55.3% of the persons with a recommendation for
      physiotherapy and only one-third with a recommendation for occupational therapy
      or logopedics received a prescription for the respective therapy in the following
      three months after examination. The age younger than 80 years, professional care,
      no home care, and-as the strongest item-preceding therapy were positively related
      to receiving a prescription. These findings show that disabled persons have the
      capability for prevention and rehabilitation, but it is used in only half of
      them. One possible reason might be the financing of the remedies, which burdens
      the budget of the health insurance, where instead the nursing care insurance
      benefits from the possible delay of the utilization of nursing care.

PMID- 16622632
TI  - [Subjective health of older people in view of the SF-36: Values from a large
      community-based sample].
AB  - This paper presents data regarding the German version of the SF-36 (Short Form 36
      Questionnaire; Bullinger and Kirchberger, 1998) that were obtained from a large
      community based sample of the German population. Results are reported for the
      elderly at the age of 60 and older from the German general population (N = 690;
      57% female). Presented are the internal consistencies of the scales (Cronbach's
      Alpha), the intercorrelations of the scales, mean values of the scales separated
      by sex, age group (60-64 years, 65-69 years, 70-74 years, 75-79 years, 80 years
      and older) and residence (Eastern and Western Germany) as well as percentile
      ranks for the whole sample.

PMID- 16622633
TI  - Filial maturity as a predictor for the burden of demented parents' caregivers.
AB  - In this study, we administered the Louvain Filial Maturity Scale [Marcoen 1993]
      to 61 adult children of demented elderly. The scores of the seven factors of this
      scale were compared to the scores of an unselected group of adult children
      examined by Marcoen. The results were taken into the context with caregiver's
      burden, and the effect of filial maturity on parents' institutionalisation was
      investigated. Marcoen's results were confirmed. Only the means of "filial help"
      and "parental consideration" differed slightly from the means of the unselected
      group. Overall, filial maturity had no influence on the caregiver's feeling of
      burden, but higher "parental consideration" resulted in lower caregiver burden.
      In addition, adult children with more "filial obligation" continued to care for
      their parents in the community more often, even when experiencing great burden
      and stress. However, institutionalisation was caused mainly by parents' growing
      needs and increasing behavioural problems. We conclude that "filial maturity"
      seems to be a very stable concept. Further investigations should focus on the
      relevance of the Louvain Filial Maturity Scale for caregiving relationship and
      also on the arrangement of the scale in order to exclude a "pseudo"-stability
      with regard to burdensome life events and situations.

PMID- 16622634
TI  - [Geriatrics in Bavaria-Database (GiB-DAT): Conception, structure and results of
      implementation (part I)].
AB  - In the year 2000, a database was implemented in Bavaria, covering the majority of
      geriatric clinics. Benchmarking statistics are generated in quarterly periods and
      scientifically analyzed. Actually, 41 of the 57 geriatric clinics in Bavaria
      participate in the project 'Geriatrics in Bavaria-Database' (GiB-DAT). For
      geriatric rehabilitation, the coverage is 82.4%. In addition, all 7 geriatric day
      clinics participate; thus, a total of 24,000 cases are documented each year.
      Therefore, GiB-DAT is the largest database for geriatric rehabilitation in
      Germany and Europe. To make documentation more effective and easy, new software
      (GERIDOCTM) has been generated which is integrated in the process of daily
      treatment. GiB-DAT offers good data quality, especially concerning completeness
      of items. This manuscript describes conception and construction of GiB-DAT and
      identifies differences compared to the Geriatric Minimum-Dataset (GEMIDAS), a
      nationwide geriatric database in Germany.

PMID- 16622635
TI  - [Geriatrics in Bavaria-Database (GiB-DAT): Basic data analysis of geriatric
      rehabilitation in Bavaria and analysis of inter-clinic variability (part II)].
AB  - OBJECTIVE: Presentation and comparison of basic data from geriatric
      rehabilitation in Bavaria with analysis of statistical influences on
      characteristic values like length of stay and Barthel Index. Are differences
      between participating clinics due to patient characteristics? SETTING: There were
      a total of 21 656 data records of the Geriatrics in Bavaria- Database (GiB-DAT)
      collected by 35 clinics within 1 year. RESULTS (PERCENTAGE OR MEAN): 70.6% female
      patients, age 80.0 years, 95.9% enrollment from acute care hospitals, length of
      stay in previous hospitals 24.3 days, length of stay in geriatric rehabilitation
      24.6 days. DIAGNOSIS: 41.7% orthopedics, 24.9% neurological, 33.4% others.
      Barthel Index on admission 44.1 points, on discharge 65.8 points (difference 21.8
      points). We found a large variance of all items between participating clinics.
      Variance for Barthel Index and length of stay is partly cleared up by regression
      analysis (multinomial logistic) and is mostly due to patient characteristics.
      CONCLUSIONS: Basic data of Bavarian geriatric rehabilitation clinics is matching
      with nationwide reference statistics. Differences exist for the lower rate of
      stroke and direct enrollment of outpatients. A simple ranking of outcome
      parameters (e. g. Barthel Index) does not make sense due to multiple influencing
      factors.

PMID- 16622636
TI  - [New use of benzodiazepines and the risk of hip fracture: A case-crossover
      study].
AB  - Benzodiazepines appear to increase the incidence of hip fractures. Their role as
      a time-dependent risk factor remains unclear. We therefore conducted a case
      crossover study to determine whether the new use of benzodiazepines is associated
      with a rise in hip fractures. We analysed 49 months of the statutory health
      insurance Gmunder Ersatzkasse (GEK) and enrolled all first hip fractures. The
      index date was the day of hospital admission. Exposure to new use of
      benzodiazepines was compared within the five periods preceding the index date.
      Out of 1630 subjects, 223 (13.7%) had at least one prescription of
      benzodiazepines in the preceding 150 days before the index date, 74 (4.5%) of
      them as a first prescription. The average age of the population was 79.8 years
      (SD: 7.7). Odds ratio (OR) of hip fracture was highest during the initial 5 days
      of new use (OR: 3.43; 95% CI 1.15-10.20) and then declined to a non-significant
      OR of 1.59 (95% CI 0.96-2.63) after 30 days. In conclusion, the start of a new
      benzodiazepine is associated with an increased risk of hip fractures. However,
      the population attributable risk (PAR) and, therefore, the percentage of
      preventable events is small (PAR: 0.55%; 95% CI 0.05-1.06%).

PMID- 16622640
TI  - [Phosphate in ophthalmologic solutions].

PMID- 16622639
TI  - Management of blood glucose in the critically ill in Australia and New Zealand: a
      practice survey and inception cohort study.
AB  - OBJECTIVE: To document current management of blood glucose in Australian and New
      Zealand intensive care units (ICUs) and to investigate the association between
      insulin administration, blood glucose concentration and hospital outcome. DESIGN
      AND SETTING: Practice survey and inception cohort study in closed multi
      disciplinary ICUs in Australia and New Zealand. PATIENTS: Twenty-nine ICU
      directors and 939 consecutive admissions to 29 ICUs during a 2-week period.
      MEASUREMENT AND RESULTS: Data collected included unit approaches to blood glucose
      management, patient characteristics, blood glucose concentrations, insulin
      administration and patient outcomes. Ten percent of the ICU directors reported
      using an intensive insulin regimen in all their patients. In 861 patients (91.7%)
      blood glucose concentration was greater than 6.1[Symbol: see text]mmol/l, 287
      (31.1%) received insulin, and the median blood glucose concentration triggering
      insulin administration was 11.5 (IQR 9.4-14) mmol/l. Univariate analysis
      demonstrated that non-survivors had a higher maximum daily blood glucose
      concentration (12 mmol/l, 9.4-14.8, vs. 9.5, 7.6-12.2) and were more likely to
      receive insulin (47% vs. 28%). Multiple logistic regression analysis showed age
      (OR per 5-year decrease 0.93, 95% CI 0.87-1.00) and APACHE II (OR per point
      decrease 0.87, 95% CI 0.84-0.90) to be independently associated with hospital
      mortality. After controlling for age and APACHE II both daily highest blood
      glucose (OR 0.95, 95% CI 0.90-1.00) and administration of insulin (OR 0.62, 95%
      CI 0.39-1.00) were independently associated when added to the model alone;
      neither was independently associated when they were simultaneously included in
      the model. CONCLUSION: Few Australian and New Zealand ICUs have adopted intensive
      insulin therapy. In this study, insulin administration and highest daily blood
      glucose concentration could not be separated in their association with hospital
      mortality.

PMID- 16622641
TI  - Oral malodor reduction by a combination of chemotherapeutical and mechanical
      treatments.
AB  - Bacterial proliferation and plaque accumulation on the surface of the tongue are
      major factors contributing to oral malodor. In this research, we used subjective
      and objective methods to evaluate the breath benefit of a triclosan-containing
      dentifrice (Blend-a-Med Complete Night) with and without tongue brushing in a
      randomized, examiner-blinded, three-period crossover clinical trial. Twenty-nine
      adults (mean age 40.2 years) with morning malodor were randomly assigned to a
      treatment sequence: triclosan dentifrice, triclosan dentifrice plus tongue
      brushing, and a control dentifrice (Crest Cavity Protection). The subjects used
      each product four times in 27 h with a 2-day wash-out period between treatments.
      Halimeter measurements were taken at baseline and at 3, 24 and 27 h. Subject
      questionnaire data assessing the breath quality were collected at 24 and 27 h.
      Both triclosan regimens showed significant improvement in oral malodor (p < 0.03)
      relative to the control. Significant (p = 0.035) malodor benefit was observed
      when tooth brushing with triclosan dentifrice was supplemented with tongue
      brushing. The triclosan dentifrice was associated with significant improvement (p
      < 0.05) in morning mouth feel and feeling of clean and fresh breath during the
      day relative to the control. There were no adverse events reported. The triclosan
      dentifrice was effective against overnight and daytime oral malodor.
      Supplementing routine brushing with tongue brushing resulted in additional breath
      improvement and breath benefits of the triclosan dentifrice were first-person
      noticeable.

PMID- 16622643
TI  - [What is practically important when carrying out a chemotherapy?].
AB  - The patient stands at the center of a chemotherapy. The aim of the curative or
      palliative treatment is not only the death of the tumor cells, but also the
      maintenance or improvement of the patient's physical condition, especially the
      improvement of quality of life. Before starting the therapy, it is necessary to
      determine, for example, the patient's general condition and motivation, and to
      carry out a consultation. Examinations, for example, blood tests, audiograms,
      renal function and lung function should also be made. Thus, the patient's
      tolerance for even the most onerous chemotherapy can be investigated and patients
      can be individually prepared for the treatment.

PMID- 16622642
TI  - [Systemic therapy of penile cancer].
AB  - Penile cancer is a rare tumor in Europe with an incidence of 0.1-0.9 per 100,000
      men per year. The success of our therapy is mainly influenced by the presence of
      lymph node metastases. At first diagnosis 17-45% of patients already harbor lymph
      node metastases. Bilateral inguinal and pelvic lymphadenectomy is a curative
      measure in these patients. In cases of gross inguinal metastases neoadjuvant
      chemotherapy leads to a remission rate of 21-60% and improves the resectability.
      The influence on survival is not proven. The same holds true for adjuvant therapy
      following lymphadenectomy. Polychemotherapy rarely leads to long-lasting complete
      remission in patients with distant metastases. The protocols consist usually of
      cisplatin, bleomycin, methotrexate, and 5-fluorouracil. The overall remission
      rate is around 15-32%. Because of the low efficacy of the present chemotherapy
      regimens, one should follow new strategies, comparable to those initiated for
      squamous cell cancer of other organs.

PMID- 16622644
TI  - [Systemic therapy of malignant adrenal tumors].
AB  - Systemic treatment of advanced-stage adrenal malignancies is most often only
      palliative. Mitotane alone or in combination with other chemotherapeutic agents
      such as cisplatin, etoposide, and vincristine are established therapeutic
      concepts for the treatment of metastatic adrenal cancer. Suramin and gossypol are
      rarely employed. New therapeutic options are tumor vaccination and treatment with
      antiangiogenic drugs. Metaiodobenzylguanidine as a radiotherapeutic drug or
      chemotherapeutic combination therapies that include cyclophosphamide,
      vincristine, and dacarbazine are applied for systemic treatment of malignant
      pheochromocytomas.. However, the clinical efficacy of the latter regimen needs
      further evaluation.

PMID- 16622645
TI  - [Systemic therapy of metastatic renal cell carcinoma].
AB  - Cytokine-based immunotherapy was the only viable option in metastatic,
      nonresectable renal cell carcinoma (RCC) for many years. Systemic immunotherapy
      has become increasingly established as a standard therapy during the last 15
      years. In this context, interleukin-2 (IL-2) and interferon-alpha (IFN-alpha)
      turned out to be the most effective single agents in RCC. Subsequently, the
      approved subcutaneous application of these compounds was the preferred
      administration route in Germany. Response rates with cytokine combination therapy
      were almost similar to those of more aggressive concepts using additional
      chemotherapeutic agents.Currently, new compounds targeting specific signaling
      pathways are readily available and have passed clinical testing. Such small
      molecules like tyrosine kinase inhibitors, monoclonal antibodies, or the mTOR
      inhibitor CCI-779 may dramatically change the established concepts of systemic
      RCC treatment. This paper gives an overview of established, current, and evolving
      concepts of systemic therapy in RCC.

PMID- 16622646
TI  - A randomized controlled trial evaluating the efficacy and safety of vitamin E
      supplementation for protection against cisplatin-induced peripheral neuropathy:
      final results.
AB  - AIM: A randomized, open label with blind assessment, controlled trial was
      performed to assess efficacy and adverse-event profile of vitamin E, given as
      supplementation for prophylaxis against cisplatin-induced peripheral neuropathy
      (CIPN). PATIENTS AND METHODS: A total of 30 patients scheduled to receive six
      courses of cumulative cisplatin-based regimens were randomly allocated to
      treatment and control groups and were then studied by means of neurological
      examination and electrophysiological study. Patients assigned to group I (n=14)
      orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3
      months after its cessation were compared to patients of group II (n=16), who
      received no vitamin E supplementation and served as controls. The severity of
      neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP)
      score. RESULTS: The incidence of neurotoxicity differed significantly between
      groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E
      supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative
      risk (RR) of developing neurotoxicity was significantly higher in case of
      controls, RR=2.51, 95% C.I.=1.16-5.47. Mean PNP scores were 4.99+/-1.33 for
      patients of group I and 10.47+/-10.62 for controls, (p=0.023). None of the
      adverse events or deaths occurred, were judged as likely to be related to the
      vitamin E supplementation. CONCLUSION: Vitamin E effectively and safely protects
      patients with cancer from occurrence of cisplatin neurotoxicity.

PMID- 16622647
TI  - Different attitudes of oncology clinicians toward truth telling of different
      stages of cancer.
AB  - OBJECTIVES: To investigate different attitudes of oncology clinicians toward
      whether and how to disclose diagnosis to patients with different stages of
      cancer. MATERIALS AND METHODS: A questionnaire investigating physician's
      demographic information and attitude toward truth telling was delivered to 256
      Chinese oncology clinicians. RESULTS: Two hundred thirty-two (90.6%) physicians
      completed the questionnaire. Of these oncology clinicians, 87.5% reported that a
      patient with early-stage cancer should be informed of the diagnosis, while only
      40.5% believed that a patient with terminal illness should know the truth
      (P<0.001). Physicians who preferred to tell the truth reported that patients with
      early or terminal stage of cancer should be informed by the doctor-in-charge
      (81.3 vs 77.7%, respectively; P>0.05), immediately after the diagnosis (83.7 vs
      87.2%, respectively), and in a quiet and undisturbed room (63.5 vs 68.1%,
      respectively; P>0.05). In stepwise multiple logistic regression analyses, no
      demographic information showed association with truth telling of early-stage
      cancer. Women doctors [odds ratio (OR), 2.25; 95% CI, 1.31 to 3.89; P=0.004] were
      more likely than men to want the patient to be informed of the terminal illness.
      Physicians with cancer relatives (OR, 0.55; 95% CI, 0.31 to 0.97; P=0.04) were
      less likely than physicians without cancer relatives to want the patient to be
      informed of the terminal illness. CONCLUSION: Oncology clinicians differed in
      their attitudes toward truth telling of different stages of cancer. Physicians
      reported that the doctor-in-charge should be the ones to disclose the condition
      of the patient, immediately after the diagnosis, and in a quiet and undisturbed
      room.

PMID- 16622648
TI  - Validity of the malnutrition screening tool as an effective predictor of
      nutritional risk in oncology outpatients receiving chemotherapy.
AB  - GOALS OF WORK: To determine the relative validity of the Malnutrition Screening
      Tool (MST) compared with a full nutrition assessment by the scored Patient
      Generated-Subjective Global Assessment (PG-SGA) and to assess MST inter-rater
      reliability in patients receiving chemotherapy. PATIENTS AND METHODS: An
      observational, cross-sectional study was conducted at an Australian public
      hospital in 50 oncology outpatients receiving chemotherapy. Inter-rater
      reliability was assessed in a subsample of 20 patients. MAIN RESULTS: According
      to PG-SGA global rating, the prevalence of malnutrition was 26%. The MST was a
      strong predictor of nutritional risk relative to the PG-SGA (100% sensitivity,
      92% specificity, 0.8 positive predictive value, 1.0 negative predictive value).
      MST inter-rater reliability was acceptable with agreement by administration
      staff/nursing staff/patient and the dietitian in 18/20 cases (kappa=0.83;
      p0.001). CONCLUSION: The MST has acceptable relative validity, inter-rater
      reliability, sensitivity, and specificity to identify chemotherapy outpatients at
      risk of malnutrition and, hence, is an acceptable nutrition screening tool in
      this patient population.

PMID- 16622649
TI  - Long-term, tunneled, noncuffed central venous catheter in cancer patients
      (Vygon): safety, efficacy, and complications.
AB  - BACKGROUND: Totally implantable or partially cuffed central venous catheters
      (CVC) are commonly used in cancer patients, but they are often expensive and may
      produce complications. To minimize costs, we have been using a low-cost,
      partially tunneled, silicone elastomer catheter with no Dacron cuff or antireflux
      valve (Vygon) since 2001. This study is a retrospective investigation of our
      experience using the Vygon catheter as a long-term CVC in patients with
      malignancy. MATERIALS AND METHODS: A total of 458 Vygon catheters (Nutricath,
      Vygon) were percutaneously inserted by an interventional radiologist in 302
      cancer patients. The median duration of catheter use was 93 days, mean 164.3 days
      (range 1-789). Main patient characteristics were as follows: number of
      male/female patients, 166/136; median age, 51 years;
      hematological/nonhematological patients, 189/113. RESULTS: Early complications
      were pneumothorax in six and hematoma in twelve of 458 implants, respectively.
      Thirteen out of 302 patients developed a catheter-related thrombosis. One hundred
      and thirty-five of 458 Vygon catheters required removal because of catheter
      related complications: 68 accidental losses, 37 cases of febrile neutropenia
      suspected to be catheter-related, ten catheter dislodgements, ten catheter
      malfunctions, four local infections, three thromboses, two catheter ruptures, and
      one allergic reaction. CONCLUSION: Vygon catheters do not seem to induce more
      early and late complications as compared with other more expensive devices,
      except for disadvantage of the high incidence rate of accidental losses.

PMID- 16622650
TI  - Alimentary mucositis: putting the guidelines into practice.
AB  - BACKGROUND: The Mucositis Study Group of the Multinational Association of
      Supportive Care in Cancer and International Society of Oral Oncology completed an
      evidence-based review of the literature for the management of alimentary
      mucositis. DISCUSSION: The present manuscript puts these guidelines into clinical
      practice by presenting two cases of alimentary mucositis from cancer therapy.
      These cases illustrate the impact of oral and gastrointestinal mucositis on
      patient care.

PMID- 16622651
TI  - G-CSF mobilised granulocyte transfusions in 32 paediatric patients with
      neutropenic sepsis.
AB  - INTRODUCTION: In this retrospective, uncontrolled, observational study, the
      effect of granulocyte colony-stimulating factor (G-CSF)-stimulated granulocyte
      transfusions (GTX) in neutropenic paediatric patients with sepsis was evaluated.
      PATIENTS AND METHODS: Granulocytes were collected from unrelated, ABO group
      matched and cytomegalic-antibody compatible donors. For neutrophil mobilization,
      donors received a single subcutaneous dose of glycosylated G-CSF (Lenograstim,
      Chugai Pharma, Japan) plus oral dexamethasone (8 mg). In total, 168 (range 1-19
      per patient) GTX were transfused in 32 children with a median age of 7.4 (0.25 to
      16) years. RESULTS: The underlying diseases comprised predominantly
      haematooncological malignancies (31 children). In 15 of 32 patients, neutropenia
      was related to allogeneic stem cell transplantation. All children suffered from
      sepsis based on international criteria (fever, tachycardia, respiratory rate >2
      SD above normal in the context of a suspected or proven infection). In ten
      children bacteria were isolated, in six children a fungal infection was diagnosed
      and four sepsis episodes were caused by viral infections. GTX contained a median
      neutrophil number of 6.3 (range 1.9-13.9)x10(10) per transfusion and obtained a
      sustained haematological response after GTX. Nineteen out of 32 children survived
      the neutropenic sepsis, particularly nine out of 11 patients with bacterial
      sepsis. DISCUSSION: In contrast to the non-survivors, we observed a significant
      decrease in the C-reactive protein levels shortly after initiation of the GTX
      treatment in the surviving patients. A clear-cut benefit of GTX for children with
      neutropenic sepsis cannot be concluded from these data, but in children with
      (severe) bacterial sepsis refractory to antibiotic treatment, GTX were feasible,
      safe and could reduce mortality rates in this subgroup of patients.

PMID- 16622652
TI  - Biologically based complementary and alternative medicine use among breast cancer
      survivors: relationship to dietary fat consumption and exercise.
AB  - Previous literature has shown that more than half of all female cancer survivors
      use some form of complementary and alternative medicine (CAM). Although the
      prevalence of CAM use in this population is becoming apparent, few researchers
      have examined the relationship between CAM use and lifestyle factors that could
      influence patients' well-being. The present study examined whether breast cancer
      survivors who use biologically based CAM are more likely than CAM nonusers to
      follow a low-fat diet and maintain moderate or vigorous exercise. Sixty-five
      female breast cancer survivors who were within 3 months of completing primary
      treatment were recruited. CAM use was measured by self-reported use of one or
      more of a list of 15 supplements. Dietary fat was measured by a 23-item self
      report measure estimating fat consumption in the past month. Dietary fat stage of
      change and moderate and vigorous exercise stage of change were assessed using
      measures based on the Transtheoretical Model of Behavior Change. Results showed
      that biologically based CAM users maintained a lower percentage of calories from
      fat in their diet (t=2.12, p<0.05), and there was a trend for CAM users to be
      more likely than CAM nonusers to be in the action or maintenance stage for
      dietary fat consumption (p<0.09). However, this study did not find that CAM users
      were more likely to be in the action or maintenance stage of change for moderate
      or vigorous exercise. These findings suggest that biologically based CAM use
      among breast cancer survivors is associated with some, but not all, healthy
      lifestyle behaviors.

PMID- 16622653
TI  - Neutropenic event risk and impaired chemotherapy delivery in six European audits
      of breast cancer treatment.
AB  - GOALS OF WORK: The aims of this study were to assess chemotherapy treatment
      characteristics, neutropenic event (NE) occurrence and related risk factors in
      breast cancer patients in Western Europe. MATERIALS AND METHODS: Six
      retrospective audits of breast cancer chemotherapy were combined into a dataset
      of 2,860 individuals. NEs were defined as neutropenia-related hospitalisation,
      dose reduction > or = 15% or dose delay > or = 7 days. Summation dose intensity
      (SDI) was calculated to compare different types of chemotherapy regimens on a
      single scale. Risk factors of NE occurrence and of low relative dose intensity
      (RDI) < or = 85% were identified by multiple logistic regression. MAIN RESULTS:
      Patient populations were comparable between audits. Until 1998, cyclophosphamide,
      methotrexate and fluorouracil regimens were most frequently used, but thereafter,
      anthracycline-based regimens were most common. NEs occurred in 20% of the
      patients and low RDI in 16%. NE occurrence predicted low RDI and was associated
      with higher age, bigger body surface area, lower body mass index, regimen type,
      more chemotherapy cycles planned, normal to high SDI, concomitant radiotherapy
      and year of treatment. First cycle NE occurrence predicted NEs from cycle 2
      onwards. A risk score using age, SDI, number of planned chemotherapy cycles and
      concomitant radiotherapy differentiated patients with increasing NE risk (9-37%).
      An alternative score version not using concomitant radiotherapy performed
      moderately less well. CONCLUSIONS: NEs occurred frequently in this combined
      dataset and they affected treatment delivery. Identifying patients at high NE
      risk enables targeted prophylaxis and may avoid dose limitations.

PMID- 16622655
TI  - Size distribution of pressure-decomposed casein micelles studied by dynamic light
      scattering and AFM.
AB  - Reversible and irreversible states of pressure-dissociated casein micelles were
      studied by in situ light scattering techniques and ex situ atomic force
      microscopy. AFM experiments performed at ambient pressure reveal heterogeneities
      across the micelle, suggesting a sub-structure on a 20 nm scale. At pressures
      between 50 and 250 MPa, the native micelles disintegrate into small fragments on
      the scale of the observed sub-structure. At pressures above 300 MPa the micelles
      fully decompose into their monomeric constituents. After pressure release two
      discrete populations of casein aggregates are observed, depending on the applied
      initial pressure: Between 160 and 240 MPa stable micelles with diameters near 100
      nm without detectable sub-structures are formed. Casein micelles exposed to
      pressures above 280 MPa re-associate at ambient pressure yielding mini-micelles
      with diameters near 25 nm. The implications concerning structural models are
      discussed.

PMID- 16622654
TI  - Comparison of hydrogen determination with X-ray and neutron crystallography in a
      human aldose reductase-inhibitor complex.
AB  - Protonation states determination by neutron (2.2 A at room temperature) and X-ray
      (0.66 A at 100 K) crystallographic studies were compared for a medium size
      enzyme, human aldose reductase (MW=36 kDa), complexed with its NADP+ coenzyme and
      a selected inhibitor of therapeutic interest. The neutron resolution could be
      achieved only with the ab initio fully deuterated protein and the subsequent
      crystallization in D2O of the complex. We used the largest good-quality crystal
      (1.00x0.67x0.23 mm, i.e. volume of 0.15 mm3) that we were able to grow so far.
      Both studies enable the determination of protonation states, with a clear
      advantage for neutrons in the case of less-ordered atoms (B>5 A2). Hydrogen atoms
      are best determined by a complementary analysis of the Fourier maps obtained from
      both methods.

PMID- 16622656
TI  - Frequency and clinicopathological characteristics of alcoholic cerebellar
      degeneration in Japan: a cross-sectional study of 1,509 postmortems.
AB  - Alcoholic cerebellar degeneration (ACD) is a pivotal neurological complication in
      alcoholics. However, although there are a few autopsy reports and some data on
      its frequency, it is considered very rare in Japan. The aims of this study were
      (1) to estimate the frequency of the disease in Japanese autopsy cases, and (2)
      to examine the clinicopathological features of symptomatic and asymptomatic cases
      of ACD. We reviewed the records of 1,509 Japanese autopsies obtained from three
      autopsy series in Japan, and selected all 55 cases (3.6%) with alcoholism. On
      neuropathological reexamination, ACD was confirmed in six male alcoholics [0.4%
      of all subjects; 10.9% of all alcoholics; mean age at death 59.3+/-13.4 years (+/
      SD)], including three asymptomatic cases. These frequencies were much lower than
      some previous Western findings, but more common than that has been expected in
      Japan. The frequencies of memory impairment and ataxia in ACD cases were
      significantly higher than those in alcoholics without any alcohol-related
      pathologies. In ACD cases, loss of Purkinje cells, narrowing of the width of the
      molecular layer, and tissue rarefaction in the granular layer were observed in
      the anterior and superior portions of the vermis of the cerebellum. In adjacent
      regions, the Purkinje cell and molecular layers were more mildly affected. The
      distribution of severely affected regions was more restricted in the asymptomatic
      cases than in the symptomatic cases. This study confirmed the frequency of
      asymptomatic cerebellar degeneration in alcoholics, suggesting that early
      intervention in alcoholism in the subclinical phase is important to prevent the
      development of cerebellar symptoms.

PMID- 16622657
TI  - Interdisciplinary child protection team work in a hospital setting.
AB  - INTRODUCTION: A retrospective study consisting of a data analysis of the Salzburg
      Child Protection Team (CPT) documentation and medical documentation was carried
      out. The objective was to investigate the frequency and distribution of
      maltreatment diagnoses and the spectrum of clinical symptoms of children reported
      to the interdisciplinary Salzburg CPT between 1996 and 2001. RESULTS AND
      DISCUSSION: The documentation covered a total of 286 children and adolescents
      (117 boys, 169 girls; mean age: 6.9+/-4.9 years) that the CPT suspected of being
      maltreated. The annual mean frequency of children reported to the CPT was 0.72%
      of all inpatients, with maltreatment being confirmed in 0.44% of the cases (61.2%
      of the children reported). The maltreatment could be classified into physical
      (26.9%), sexual (14.0%), neglect (17.5%) and Munchhausen's syndrome by proxy
      (2.4%). In 17.5% of the suspected cases the suspicion of maltreatment was
      subsequently judged to be incorrect, while in 21.7% of the cases, doubt remained.
      In 43% of all cases the suspected perpetrators were one or both parents, and in
      8.3% the perpetrator was a person from outside the family. The police were
      informed in 20.3% of the cases, and the Youth Welfare Department was informed in
      62.6% of the cases. In conclusion, the frequency of maltreatment diagnoses is
      lower than expected. CONCLUSION: Although the work of CPT can be considered to be
      effective and useful, better diagnostic selectivity and specificity and a long
      term follow-up are required.

PMID- 16622658
TI  - Decision-making in pediatrics: a practical algorithm to evaluate complementary
      and alternative medicine for children.
AB  - We herein present a preliminary practical algorithm for evaluating complementary
      and alternative medicine (CAM) for children which relies on basic bioethical
      principles and considers the influence of CAM on global child healthcare. CAM is
      currently involved in almost all sectors of pediatric care and frequently
      represents a challenge to the pediatrician. The aim of this article is to provide
      a decision-making tool to assist the physician, especially as it remains
      difficult to keep up-to-date with the latest developments in the field. The
      reasonable application of our algorithm together with common sense should enable
      the pediatrician to decide whether pediatric (P)-CAM represents potential harm to
      the patient, and allow ethically sound counseling. In conclusion, we propose a
      pragmatic algorithm designed to evaluate P-CAM, briefly explain the underlying
      rationale and give a concrete clinical example.

PMID- 16622659
TI  - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): clinico
      pathological study of three cases.
AB  - INTRODUCTION: We report three cases of sinus histiocytosis, a rare disease of
      unknown aetiology with massive lymphadenopathy (SHML), also known as Rosai
      Dorfman (RD) disease, in a paediatric population. This proliferative histiocytic
      disorder is defined by histological and immunohistochemical (IHC) characteristics
      and can manifest as nodal involvement with variable enlargement of the lymph
      nodes (two cases) and extranodal manifestations involving skin and larynx
      involvement (one case). One patient had hypergammaglobulinemia. The morphological
      investigation revealed that all lymph nodes showed hyperplasia of sinuses with
      abundant histiocytic cell with intracytoplasmic lymphocytes. Skin and larynx
      biopsies showed a histiocyte and lymphocyte infiltrate with similar
      characteristics. An ultrastructural study was carried out on material from one
      patient. In the IHC study, SHML cells expressed phagocytic markers such as CD68
      and S100, but markers for Langerhan's (CD1a) or dendritic cells (DRC, CD23 and
      CNA42) were absent. Two patients had a complete remission after surgical excision
      and no other treatment, but the third patient was treated with radiotherapy after
      a relapse with obstruction of the upper airway. CONCLUSION: This disorder must be
      considered in the differential diagnosis of young patients who exhibit massive or
      multiple lymphadenopathies, especially when involvement of the cervical area
      occurs. Due to the good outcome of the disease, a conservative approach is
      justified.

PMID- 16622660
TI  - The effect of vitamin K supplementation on biochemical markers of bone formation
      in children and adolescents with cystic fibrosis.
AB  - INTRODUCTION: Impaired vitamin K status in cystic fibrosis (CF) has been
      considered as a newly emerged pathogenetic factor for reduced bone mineral
      density (BMD). OBJECTIVES: Our aim was to evaluate the effectiveness of vitamin K
      supplementation in managing bone formation abnormalities in children and
      adolescents with CF. MATERIALS AND METHODS: The statuses of vitamins K and D in
      relation to biochemical markers of bone metabolism and BMD were examined in 20 CF
      children receiving vitamin D supplements but not vitamin K supplements.
      Laboratory tests were carried out at the beginning of the study period and after
      1 year of vitamin K supplementation (10 mg single oral dose/week) and the results
      were compared; the results were also compared with those of 25 healthy controls.
      RESULTS AND DISCUSSION: Ten of the CF patients had BMD z-score<or=2.5 (n=5) or
      between -1 and -2.5 (n=5). Biochemical tests on patients before vitamin K
      supplementation revealed that the levels of osteoblastic activity markers,
      namely, bone alkaline phosphatase (BAP), serum osteocalcin (Gla-OC), serum
      carboxy-terminal propeptide of type I procollagen (PICP) and serum amino-terminal
      propeptide of type I procollagen (PINP), were significantly reduced compared with
      those of the controls. These patients had also lower 25-hydroxy-vitamin D
      (25(OH)D) and vitamin K serum levels, higher undercaboxylated osteocalcin (Glu
      OC) and parathormone (PTH) levels and a higher calcium to creatinine ratio
      (Ca/Cr) than the controls. Vitamin K intake was associated with an increase in
      Gla-OC, PINP, PICP levels and a decrease in Glu-OC levels. PTH levels were lower
      after vitamin K supplementation without any difference in BMD z-scores.
      CONCLUSION: Our data indicate that vitamin K supplementation may have a
      beneficial role in bone health in CF children.

PMID- 16622661
TI  - Cockroach sensitisation in Belgian children.

PMID- 16622662
TI  - Assessment of implementation of a standardized parenteral formulation for early
      nutritional support of very preterm infants.
AB  - INTRODUCTION: Parenteral nutrition (PN) plays an important role in the
      nutritional support of very preterm newborns. It has been suggested that a high
      proportion of PN orders could be standardized. In 2002, we implemented in our
      unit the preparation of three standardized formulations for PN adapted to the
      nutritional requirements of premature infants<32 weeks. Following this change of
      practice, a retrospective observational study was conducted to evaluate the
      relevance of the implemented standardized PN regime. Twenty premature inborn
      infants<32 weeks gestation who had received standardized (STD) PN in 2003 were
      matched for 20 infants who had received individualized (IND) PN in 2001. Adequacy
      of nutrition was assessed by comparing daily intravenous nutrient intake and
      biochemical parameters during the first week. Amino-acid intakes on day 3 were
      higher in the STD group (1.5+/-0.2 g/kg/d vs. 0.9+/-0.5, p<0.001), and the
      calcium phosphate intakes were better balanced. The cumulated intake of amino
      acids for the first week was greater in the STD group (+20% ; p=0.0003).
      Biochemical parameters were similar in both groups. Insulin infusions were less
      frequent in the STD group (p<0.06). CONCLUSION: Standardized parenteral
      formulations provided higher early intakes of amino acid and glucose, a better
      calcium phosphate ratio, and a greater amount of amino-acid intakes during the
      first week while maintaining the same biochemical parameters. This strategy forms
      part of an approach concerning quality control and the respect of good
      professional practice for the preparation of parenteral nutrition solutions.

PMID- 16622663
TI  - Late-presenting congenital diaphragmatic hernia associated with ectopic thoracic
      kidney.
AB  - Although congenital defects of diaphragma often occur in the period immediately
      following birth, 10-20% of these cases are diagnosed later. We report on a 7
      month-old male infant with late-presenting congenital diaphragmatic hernia
      associated with a thoracic ectopic kidney. We conclude that congenital
      diaphragmatic defects should be considered in young children with respiratory
      distress and that computerized tomography is a noninvasive and accurate
      diagnostic method in the evaluation of additional abnormalities in these
      patients.

PMID- 16622664
TI  - ANCA-associated diffuse alveolar hemorrhage due to benzylthiouracil.
AB  - Benzylthiouracil has been recently observed to be associated with antineutrophil
      cytoplasmic antibody-positive vasculitis, resulting in crescentic
      glomerulonephritis. We report an 8-year-old girl treated with benzylthiouracil
      for Graves's disease who developed an ANCA-positive vasculitis with pulmonary
      hemorrhage. She responded to corticosteroids and discontinuation of
      benzylthiouracil. This represents the first pediatric case of benzylthiouracil
      induced diffuse alveolar hemorrhage.

PMID- 16622665
TI  - F-18 FDG-PET imaging and correlation with CT in staging and follow-up of
      pediatric lymphomas.
AB  - BACKGROUND: We hypothesized that F-18 FDG-PET could be a useful, functional
      imaging modality for assessing the initial staging, response to therapy and
      follow-up of children diagnosed with lymphoma. OBJECTIVE: To assess the role of
      whole-body F-18 FDG-PET imaging in patients with lymphoma as an initial staging
      modality and to measure its predictive value for monitoring the response to
      therapy and disease recurrence compared to CT and clinical follow-up studies.
      MATERIALS AND METHODS: As part of their routine clinical care, 24 patients with
      histologically proven lymphoma (18 Hodgkin disease and 6 non-Hodgkin lymphoma)
      underwent an F-18 FDG-PET and a CT scan. A total of 28 studies were performed and
      the entire set of scans retrospectively reviewed. Seven studies were performed
      for initial staging, 12 for monitoring therapy response and 9 for detecting
      recurrence. Initial diagnosis was confirmed by histopathology while the gold
      standard at follow-up was established by clinical follow-up, additional imaging
      modalities and/or biopsy. F-18 FDG-PET was visually compared to CT on a lesion-by
      lesion basis. Fifteen anatomic regions (seven nodal and eight extranodal) were
      analyzed. RESULTS: Of the 414 regions analyzed, PET and CT were concordant in 366
      (positive in 16 and negative in 350). Discordance was found in 48 regions.
      Overall sensitivities, specificities, and positive and negative predictive values
      were 78%, 98%, 94% and 90% for F-18 FDG-PET and 79%, 88%, 90% and 46% for CT,
      respectively. CONCLUSION: F-18 FDG-PET imaging is a useful technique for the
      staging and follow-up of pediatric patients with lymphoma.

PMID- 16622667
TI  - Residual posterior femoral condyle osteophyte affects the flexion range after
      total knee replacement.

PMID- 16622666
TI  - Imaging of conjoined twins.
AB  - The incidence of conjoined twins is estimated to be around 1 in 250,000 live
      births. There is a distinct female predominance. In this paper the imaging of
      conjoined twins both antenatally and postnatally is reviewed, in particular
      taking into consideration recent advances with multidetector CT. Accurate
      counselling of parents regarding the likely outcome of the pregnancy and the
      likelihood of successful separation is dependent on good prenatal imaging with
      ultrasound and MRI. Planning of postnatal surgical separation is aided by
      accurate preoperative imaging which, depending on the conjoined area, will
      encompass many imaging modalities, but often relies heavily on CT scanning.

PMID- 16622668
TI  - Ethnic differences in preoperative function of patients undergoing total knee
      arthroplasty.
AB  - The prevalence of osteoarthritis is high in all ethnic and demographic groups.
      The timing of surgery is important because poor preoperative functional status is
      related to poor postoperative function. The aim of our study was to compare the
      preoperative knee function in patients of Asian origin with that of Caucasians
      living in the same community. We carried out a prospective study of 63
      consecutive Asian patients and 63 age- and gender-matched Caucasian patients
      undergoing total knee arthroplasty. Preoperative Knee Society Clinical Rating
      System scores were recorded as a separate knee score and knee function score. The
      mean preoperative knee score in Asian patients was 37.6 compared with 41.5 in
      Caucasians (p<0.12); this difference was not statistically significant. The mean
      preoperative knee function score in Asian patients was 32.5 compared with 45.0 in
      Caucasians (p<0.00015); this difference was highly statistically significant. We
      conclude that patients of Asian origin undergoing total knee arthroplasty have
      lower preoperative knee function than Caucasians do. Cultural beliefs and social
      support partially explain this discrepancy, but health care providers must
      attempt to educate patients and close family members about the importance of
      timing the surgery to obtain the optimum benefits of pain relief and function.

PMID- 16622669
TI  - Clinical outcome after transfixation of the epiphysis with Kirschner wires in
      unstable slipped capital femoral epiphysis.
AB  - Treatment of slipped capital femoral epiphysis (SCFE) is still controversial.
      Agreement has not yet been reached on the appropriate time to perform surgery,
      the necessity of repositioning manoeuvres, the type of implants for
      stabilisation, or the need for prophylactic treatment of the contralateral side.
      In this retrospective study, we present 29 patients with unstable (acute and
      acute-on-chronic) SCFE treated by internal fixation of the epiphysis with three
      or four Kirschner wires both therapeutically on the affected side and
      prophylactically on the not (yet) affected side. After hardware removal and mean
      follow-up of 3.5 years, radiological and clinical examination of hip function was
      carried out. X-ray in two planes showed no incidence of any slip progression.
      Applying the score used by Heyman and Herndon, 18 results (62.1%) were classified
      as excellent, nine (31.1%) as good, one (3.4%) as fair, and one (3.4%) as poor.
      The rate of severe complications such as chondrolysis and avascular necrosis of
      the femoral head was low in our series (0% and 6.8%, respectively). This form of
      therapeutic management shows good clinical results with low complication rates.
      The slip can be efficiently stabilised, progression is reliably prevented, and
      remodelling of the joint gives the patient good overall hip function. We see no
      indication for emergency surgery.

PMID- 16622671
TI  - Percutaneous pinning using threaded pins as a treatment option for unstable two-
      and three-part fractures of the proximal humerus: a retrospective study.
AB  - A retrospective study was designed to evaluate the results of closed reduction
      and percutaneous pinning using threaded pins as a treatment option for fractures
      of the humeral head. Patients who suffered two- and three-part fractures of the
      proximal humerus treated by this method of fixation were included. Fifty patients
      (32 females and 18 males) with an average age of 50 years were clinically
      evaluated at an average of 2.5 years after this procedure (range 1-4 years). The
      Constant score was used to evaluate the clinical outcome. Preoperative and
      postoperative X-rays were also assessed. Out of 50 patients, 18 (36%) obtained
      excellent results, 17 (34%) good results, eight (16%) fair results and seven
      (14%) achieved only poor results. The average Constant score was 81 (range 60
      100). Fractures confined to the surgical or anatomical neck generally did better
      than those associated with a greater tuberosity fragment (average score 86 versus
      78). Patients who required shaft stabilisation and in addition to reduction and
      fixation of the greater tuberosity showed a lower average score (68). There were
      no cases of avascular necrosis, neurovascular complications or deep infections. A
      significant loss of fracture position due to failure of internal fixation
      occurred in seven cases, three of these patients underwent revision surgery.
      Closed reduction and percutaneous pinning offers a good fracture position and
      stability with minimal soft tissue damage. We recommend that displaced two- and
      three- part fractures of the humeral head should be treated in this manner.
      However these patients should be monitored closely for a period of four weeks,
      since secondary displacement and failure of fixation can occur in this period.
      Careful patient selection may minimise these complications.

PMID- 16622672
TI  - Post-discectomy syndrome treated with lumbar interbody fusion.
AB  - We studied 27 patients with post-discectomy syndrome. All patients had Lumbar
      Interbody Fusion with titanium cages and pedicle screw fixation either as
      Anterior (ALIF, n=18) or as Transforaminal Lumbar Interbody Fusion (TLIF, n=9).
      Follow-up ranged from 24 to 94 months. The clinical and radiological data were
      compared. The outcome was evaluated using the Oswestry low back pain disability
      score and the visual analogue pain intensity scale. Outcomes were similar for all
      patients regardless of surgical technique and showed a significant improvement at
      final follow-up.

PMID- 16622673
TI  - Aluminium speciation in environmental samples: a review.
AB  - Because of its toxic effects on living beings, Al may represent an environmental
      hazard, particularly under increased acidic conditions. Growing environmental
      concern over the presence of increased Al concentrations in soil solutions and
      fresh waters resulted in the development of numerous analytical techniques for
      the determination of Al species. Al has a very complex chemistry that is
      significantly influenced by pH. Different Al species are present in environmental
      solutions, and many of them are unstable. Contamination of samples and reagents
      by extraneous Al represents an additional problem in speciation of Al at trace
      concentrations. Due to these reasons quantitative determination of particular
      chemical forms of Al is still a very difficult task for analytical chemists. The
      most important analytical methodologies of the last decade and new trends for the
      speciation of Al in environmental samples are comprehensively reviewed here.

PMID- 16622674
TI  - Orthogonal projection (OP) technique applied to pattern recognition of
      fingerprints of the herbal medicine houttuynia cordata Thunb. and its final
      injection products.
AB  - It is a crucial issue to determine the origins of herbal medicinal materials and
      identify the quality grades and fakes of their final products collected from
      different pharmaceutical corporations. Pattern recognition technique may assist
      the manufacturers to achieve this purpose and effectively control the quality of
      their products. In this work, a widely used method in chemometrics, orthogonal
      projection (OP) technique, was applied to discrimination analysis and
      identification of fingerprints of the herbal medicine houttuynia cordata Thunb.
      (HCT) and its final injection products. The advantages of the OP technique are
      clearly shown after comparing with the conventional methods such as principal
      component analysis (PCA), Mahalanobis distance (MD), and similarity comparison
      method (SCM). Three different sources of medicinal material HCT and its final
      injection products from six different manufacturers were studied under 'sixfold',
      'threefold' and 'threefold-bis' cross-validation procedures. The good performance
      of the proposed method in determination and identification of unknown samples
      shows it could be a powerful tool for quality control in herbal medicine
      production and other related research fields.

PMID- 16622675
TI  - Quantitative plasma determination of a novel antiretroviral derivative of
      zidovudine by solid-phase extraction and high-performance liquid chromatography.
AB  - A solid-phase extraction methodology, followed by high-performance liquid
      chromatography (HPLC) quantification with UV absorbance detection (lambda = 267
      nm), was developed in order to study the stability of 3'-azido-3'-deoxy-5'-O
      isonicotinoylthymidine (AZT-Iso), a novel derivative of the antiretroviral AZT,
      in different matrixes. The half-lives (t1/2) for AZT-Iso were 1.19, 1.13 and 0.30
      h for human, rat and rabbit plasma, respectively, and 14.91 and 25.49 h for
      potassium phosphate buffer (pH 7.4) and human serum albumin solution,
      respectively. The HPLC method proved to be selective, sensitive and accurate.
      Good recovery, linearity and precision were achieved using p-fluorophenol as an
      internal standard. The validity of this method was tested using synthetic
      mixtures of the intact drug with its decomposition products. In conclusion, the
      method presented is applicable to in vivo pharmacokinetics studies of AZT-Iso in
      rats.

PMID- 16622676
TI  - Influence of laser wavelength on LIBS diagnostics applied to the analysis of
      ancient bronzes.
AB  - In this work the influence of laser wavelength upon the analytical results
      obtained from applying LIBS diagnostics to bronzes was investigated theoretically
      and experimentally at 1,064 nm and 355 nm. The laser ablation process was modeled
      for a set of reference samples of quaternary Cu/Sn/Pb/Zn alloys and the
      difference between plume composition and known target stoichiometry was estimated
      for both of the wavelengths considered. LIBS measurements were performed on the
      same set of reference samples and under the same experimental conditions to
      validate the model at different wavelengths. Results from the application of the
      model to calculate sample optical properties during laser irradiation, absorption
      in the plasma and plasma temperature are also presented.

PMID- 16622677
TI  - The role of reduced iron powder in the fermentative production of tetanus toxin.
AB  - When tetanus toxin is made by fermentation with Clostridium tetani, the
      traditional source of iron is an insoluble preparation called reduced iron
      powder. This material removes oxygen from the system by forming FeO(2) (rust).
      When inoculated in a newly developed medium lacking animal and dairy products and
      containing glucose, soy-peptone, and inorganic salts, growth and toxin production
      were poor without reduced iron powder. The optimum concentration of reduced iron
      powder for toxin production was found to be 0.5 g/l. Growth was further increased
      by higher concentrations, but toxin production decreased. Inorganic iron sources
      failed to replace reduced iron powder for growth or toxin formation. The iron
      source that came closest was ferrous ammonium sulfate. The organic iron sources
      ferric citrate and ferrous gluconate were more active than the inorganic
      compounds but could not replace reduced iron powder. Insoluble iron sources, such
      as iron wire, iron foil, and activated charcoal, were surprisingly active.
      Combinations of activated charcoal with soluble iron sources such as ferrous
      sulfate, ferric citrate, and ferrous gluconate showed increased activity, and the
      ferrous gluconate combination almost replaced reduced iron powder. It thus
      appears that the traditional iron source, reduced iron powder, plays a double
      role in supporting tetanus toxin formation, i.e., releasing soluble sources of
      iron and providing an insoluble surface.

PMID- 16622678
TI  - Efficient production of laccases by Trametes sp. AH28-2 in cocultivation with a
      Trichoderma strain.
AB  - A biocontrol fungus isolated from rotting wood was identified as a Trichoderma
      strain (named as Trichoderma sp. ZH1) by internal transcribed spacer (ITS)
      sequences of rRNA genes. The laccase yield of Trametes sp. AH28-2 in
      cocultivation with Trichoderma sp. ZH1 reached 6,210 U l(-1), approximately
      identical to those induced by toxic aromatic inducers. Cocultures maintained 60
      70 % of their highest laccase activity obtained at 5 days after inoculation of
      the biocontrol fungus, at least for 20 days. Furthermore, a novel laccase isozyme
      (LacC) was obtained through the fungal interactions. The molecular weight of LacC
      is about 64 kDa, and its isoelectric point is 6.6. The temperature and pH optimum
      for LacC to oxidize guaiacol are 55 degrees C and 5.0, respectively. LacC is
      stable both at 60 degrees C and pH 4.0-8.0. Furthermore, the K (m) values of LacC
      for various substrates were also determined. Our work demonstrates a safe
      strategy for the production of industrial laccases, instead of the traditional
      method of chemical induction.

PMID- 16622679
TI  - Decolorization of triphenylmethane, azo, and anthraquinone dyes by a newly
      isolated Aeromonas hydrophila strain.
AB  - A broad-spectrum dye-decolorizing bacterium, strain DN322, was isolated from
      activated sludge of a textile printing wastewater treatment plant. The strain was
      characterized and identified as a member of Aeromonas hydrophila based on Gram
      staining, morphology characters, biochemical tests, and nearly complete sequence
      analysis of 16S rRNA gene and the gyrase subunit beta gene (gyrB). Strain DN322
      decolorized a variety of synthetic dyes, including triphenylmethane, azo, and
      anthraquinone dyes. For color removal, the most suitable pH and temperature were
      pH 5.0-10.0 and 25-37 degrees C, respectively. Triphenylmethane dye, e.g.,
      Crystal Violet, Basic Fuchsin, Brilliant Green, and Malachite Green (50 mg l(-1))
      were decolorized more than 90% within 10 h under aerobic culture condition and
      Crystal Violet could be used as sole carbon source and energy source for cell
      growth. The color removal of triphenylmethane dyes was due to a soluble cytosolic
      enzyme, and the enzyme was an NADH/NADPH-dependent oxygenase; For azo and
      anthraquinone dyes, e.g., Acid Amaranth, Great Red GR, Reactive Red KE-3B, and
      Reactive Brilliant Blue K-GR (50 mg l(-1)) could be decolorized more than 85%
      within 36 h under anoxic condition. This strain may be useful for bioremediation
      applications.

PMID- 16622680
TI  - Identification of different tumor escape mechanisms in several metastases from a
      melanoma patient undergoing immunotherapy.
AB  - The cytotoxic activity of T cells selects the outgrowth of tumor cells that
      escape from immune surveillance by different strategies. The different mechanisms
      that interfere with immune recognition and limit vaccination efficiency are still
      poorly understood. We analysed six cell lines established from different
      metastases of melanoma patient UKRV-Mel-20 for specific characteristics known to
      have an impact on the tumor-T cell interaction: (1) alterations in the HLA class
      I phenotype, (2) expression of Fas/CD95, and (3) expression of specific cytokines
      and chemokines. One of the cell lines, UKRV-Mel-20f, exhibited an HLA class I
      haplotype loss and just this cell line was also characterised by the expression
      of Fas/CD95 and of relatively high levels of proinflammatory chemokines
      suggesting that the cytotoxic activity of tumor-infiltrating T cells might have
      selected the outgrowth of this tumor cell variant. All other cell lines analysed
      showed no alterations in HLA class I expression, but, in contrast to UKRV-Mel
      20f, expressed much lower levels of Fas/CD95 and of proinflammatory chemokines
      and some of them produced high levels of immunosuppressive TGF-beta1. These
      results suggest that in patient UKRV-Mel-20, tumor cells interfere with T cell
      recognition by different strategies which might partially explain why this
      patient did not have a clinical response to an autologous tumor cell vaccine.

PMID- 16622681
TI  - STEAP, a prostate tumor antigen, is a target of human CD8+ T cells.
AB  - STEAP is a recently identified protein shown to be particularly overexpressed in
      prostate cancer and also present in numerous human cancer cell lines from
      prostate, pancreas, colon, breast, testicular, cervical, bladder and ovarian
      carcinoma, acute lymphocytic leukemia and Ewing sarcoma. This expression profile
      renders STEAP an appealing candidate for broad cancer immunotherapy. In order to
      investigate if STEAP is a tumor antigen that can be targeted by specific CD8(+) T
      cells, we identified two high affinity HLA-A*0201 restricted peptides (STEAP(86
      94) and STEAP(262-270)). These peptides were immunogenic in vivo in HLA-A*0201
      transgenic HHD mice. Peptide specific murine CD8 T cells recognized COS-7 cells
      co-transfected with HHD (HLA-A*0201) and STEAP cDNA constructs and also HLA
      A*0201(+) STEAP(+) human tumor cells. Furthermore, STEAP(86-94) and STEAP(262
      270) stimulated specific CD8(+) T cells from HLA-A*0201(+) healthy donors, and
      these peptide specific CD8(+) T cells recognized STEAP positive human tumor cells
      in an HLA-A*0201-restricted manner. Importantly, STEAP(86-94)-specific T cells
      were detected and reactive in the peripheral blood mononuclear cells in NSCLC and
      prostate cancer patients ex vivo. These results show that STEAP can be a target
      of anti-tumor CD8(+) T cells and that STEAP peptides can be used for a broad
      spectrum-tumor immunotherapy.

PMID- 16622683
TI  - The ionic dependence of voltage-activated inward currents in the pharyngeal
      muscle of Caenorhabditis elegans.
AB  - The pharynx of Caenorhabditis elegans consists of a syncytium of radially
      orientated muscle cells that contract synchronously and rhythmically to ingest
      and crush bacteria and pump them into the intestine of the animal. The action
      potentials that support this activity are superficially similar to vertebrate
      cardiac action potentials in appearance with a long, calcium-dependent plateau
      phase. Although the pharyngeal muscle can generate action potentials in the
      absence of external calcium ions, action potentials are absent when sodium is
      removed from the extracellullar solution (Franks et al. 2002). Here we have used
      whole cell patch clamp recordings from the pharynx and show low voltage-activated
      inward currents that are present in zero external calcium and reduced in zero
      external sodium ions. Whilst the lack of effect of zero calcium when sodium ions
      are present is not surprising in view of the known permeability of voltage-gated
      calcium channels to sodium ions, the reduction in current in zero sodium when
      calcium ions are present is harder to explain in terms of a conventional voltage
      gated calcium channel. Inward currents were also recorded from egl-19 (n582)
      which has a loss of function mutation in the pharyngeal L-type calcium channel
      and these were also markedly reduced in zero external sodium. Despite this
      apparent dependence on external sodium ions, the current was partially blocked by
      the divalent cations, cadmium, barium and nickel. Using single-channel recordings
      we identified a cation channel for which the open-time duration was increased by
      depolarisation. In inside-out patches, the single-channel conductance was highest
      in symmetrical sodium solution. Further studies are required to determine the
      contribution of these channels to the pharyngeal action potential.

PMID- 16622684
TI  - The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF
      rats.
AB  - AIMS/HYPOTHESIS: The metabolic and endocrine disturbances associated with obesity
      and type 2 diabetes may impair the normal metabolic response to injury. Our
      objective was to investigate amino acid metabolism in endotoxaemic type 2
      diabetic obese rats. MATERIALS AND METHODS: A metabolic study was performed over
      4 days using male Zucker diabetic fatty (ZDF) rats (fa/fa) and lean littermates
      (fa/+) divided into three groups: ad libitum-fed groups which underwent no
      treatment, lipopolysaccharide (LPS)-treated groups receiving E. coli LPS by i.p.
      injection, and pair-fed groups to the respective LPS groups. We evaluated the
      effect of endotoxaemia on body weight, food intake and tissue weights. Nitrogen
      loss and muscular proteolysis were measured daily by determination of urinary 3
      methylhistidine (3-MH) excretion. Plasma, intestine and muscle amino acid levels
      were measured. RESULTS: The data showed that ad libitum-fed ZDF rats had lower
      plasma arginine and glutamine levels than ad libitum-fed control rats. Compared
      with control rats, the LPS-treated ZDF rats presented lower thymic involution, a
      lower 3-MH:creatinine ratio and higher cumulative nitrogen balance.
      CONCLUSIONS/INTERPRETATION: Against our working hypothesis, ZDF rats did not show
      an impaired metabolic response, and even appeared to be less sensitive to the
      stress.

PMID- 16622685
TI  - Paget's disease of the nipple diagnosed by MRI.
AB  - BACKGROUND: Paget's disease of the breast is a rare manifestation of breast
      carcinoma. CASE REPORT: The patient presented with a red lesion of the left
      nipple-areola complex. Breast physical examination, ultrasonography and
      mammography were normal bilaterally. Magnetic resonance imaging (MRI) correctly
      depicted Paget's disease of the nipple. Before surgery the patient underwent
      biopsy of the lesion that showed Paget's disease of the breast associated with an
      underlying ductal carcinoma in situ. The patient underwent left mastectomy and
      unilateral axillary lymph node dissection. The patient refused the breast
      conserving surgery because she was afraid that she could have a recurrence of the
      carcinoma. Microscopy of the lesion confirmed the MRI diagnosis. CONCLUSION: MRI
      was very useful and accurate to diagnose Paget's disease of the breast without
      palpable mass, ultrasonographic and mammographic findings.

PMID- 16622686
TI  - A new technique for localization of hepatic tumors that are poorly visible with
      CT fluoroscopy.
AB  - The purpose of this study was to report a new technique for localization of
      hepatic tumors that are poorly visible with CT fluoroscopy. Forty-three
      hepatocellular carcinomas were not visible with CT fluoroscopy. A 22-gauge Chiba
      end-hole needle was inserted in the approximate location of a lesion estimated on
      the basis of anatomical landmarks demonstrated on both previous MR and CT images.
      We injected 3 ml of a mixture of nonionic contrast material and saline solution.
      Following the first injection, contrast solution filled the hepatic lesion in 29
      of 43 cases. In 8 of 43 cases, contrast solution was distributed in the normal
      surrounding liver. In 7 of these 8 cases, repositioning allowed us to adjust the
      needle in the tumor. In the other 6 of 43 cases, contrast solution spread within
      capsule or pseudocapsule (pattern 3). In all 6 cases, repositioning allowed to
      adjust the needle in the tumor. This new technique allows an accurate
      localization of hepatic tumors that are poorly visible with CT fluoroscopy.

PMID- 16622687
TI  - Value of virtual tracheobronchoscopy and bronchography from 16-slice
      multidetector-row spiral computed tomography for assessment of suspected
      tracheobronchial stenosis in children.
AB  - PURPOSE: To evaluate the value of dose-reduced 16-slice multidetector-row spiral
      computed tomography (16-MDCT) using virtual tracheobronchoscopy (VTB) and virtual
      bronchography (VBG) in children with suspected tracheobronchial stenosis.
      MATERIALS AND METHODS: 12 children (4 d to 3 years, body weight 1.2 kg to 13.5
      kg) with stridor and suspected tracheobronchial stenosis were examined by
      contrast-enhanced low-dose 16-MDCT. Conventional axial slices, MPRs, VTB, and VBG
      were calculated. Image findings were correlated with the results of fiberoptic
      bronchoscopy (12 out of 12) as a gold standard and subsequent surgery (8 out of
      12). RESULTS: VTB and VBG demonstrated the fiberoptic bronchoscopically suspected
      tracheal stenosis in 11 of 12 children due to vascular compression because of the
      brachiocephalic trunk (6), a double aortic arch (2), a vascular compression of
      the left main bronchus (2), and a right aberrant subclavian artery (1). Eleven
      out of 12 stenoses were correctly depicted by conventional axial slices, MPRs,
      VTB, and VBG. Dose reduction was 79 to 85.8% compared to a standard adult chest
      CT. CONCLUSION: Dose-reduced 16-MDCT with the use of VTB and VBG is effective for
      the evaluation of tracheobronchial stenosis in children and correlates well with
      fiberoptic bronchoscopy.

PMID- 16622688
TI  - Total-body MR-imaging in oncology.
AB  - Although MRI is an effective modality in oncology, state-of-the-art total-body
      MRI (TB-MRI) in the past was infeasible in the diagnostic work-up, due to the
      need for repeated examinations with repositioning and separate surface coils to
      cover all body parts. To overcome this limitation, either a moving table platform
      in combination with the body-coil or a special designed rolling table platform
      with one body phased-array coil have been implemented with promising results for
      both tumor staging and metastases screening. Since 2004, state-of-the-art TB-MR
      imaging with high spatial resolution has become feasible using a newly developed
      1.5 Tesla TB-MRI system with multiple receiver channels. This review gives an
      overview based on the recent literature as well as our own experience concerning
      the possibilities, challenges, and limitations of TB-MRI in oncology, emphasizing
      both oncological staging and early tumor detection in asymptomatic subjects.

PMID- 16622689
TI  - Primary pulmonary artery aneurysm in tuberous sclerosis: CT, angiography and
      pathological study.

PMID- 16622690
TI  - Staging of Klatskin tumours (hilar cholangiocarcinomas): comparison of MR
      cholangiography, MR imaging, and endoscopic retrograde cholangiography.
AB  - The aim of the study was to compare prospectively magnetic resonance
      cholangiography (MRC) and magnetic resonance imaging (MRI) with endoscopic
      retrograde cholangiography (ERC) in the diagnosis and staging of Klatskin tumours
      of the biliary tree (hilar cholangiocarcinomas). Forty-six patients with
      suspected Klatskin tumours of the biliary tract underwent MRI and heavily T2
      weighted, non-breathhold, respiratory-triggered fast spin-echo MRC. Forty-two
      patients underwent ERC within 24 h; in four patients, ERC was not feasible, and
      percutaneous trans-hepatic cholangiography (PTC) was carried out instead. Two
      independent investigators evaluated imaging results for the presence of tumour,
      bile duct dilatation, and stenosis. Clinical and histopathological correlation
      revealed Klatskin tumours in 33 patients. MRI revealed a slightly hyperintense
      signal of infiltrated bile ducts in T2-weighted fast spin-echo sequences. The
      malignant lesion was regularly visualized as a hypointense area in T1-weighted
      gradient-echo sequences with substantial contrast enhancement along the involved
      bile duct walls. MRC revealed the location and extension of the tumour in 31 of
      33 cases correctly (sensitivity 94%, specificity 100%, diagnostic accuracy 95%).
      In 27 of 31 cases, ERC enabled accurate staging and diagnosis of Klatskin tumours
      with a sensitivity of 87%. ERC and PTC combined yielded a sensitivity of 84% and
      a specificity of 97%. Tumours were grouped according to the Bismuth
      classification, with MRC allowing correct identification of type I tumour in
      seven patients, type II tumour in four patients, type III tumour in 12 patients,
      and type IV tumour in ten patients. MRC provided superior visualization of
      completely obstructed peripheral systems. MRC in combination with MRI is a
      reliable non-invasive diagnostic method for the pre-therapeutic staging of
      Klatskin tumours.

PMID- 16622691
TI  - A phase I-II study of bi-weekly gemcitabine and irinotecan as second-line
      chemotherapy in non-small cell lung cancer after prior taxane + platinum-based
      regimens.
AB  - PURPOSE: Treatment options in patients with recurrent non-small cell lung cancer
      (NSCLC) remain limited as a result of poor activity of most agents after failure
      of platinum-based therapy. In the present phase I-II study, we evaluated the
      feasibility and efficacy of bi-weekly gemcitabine (GEM) + irinotecan (CPT-11) in
      patients with relapsed NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC,
      WHO-performance status (PS) </= 2, prior taxane/platinum-based chemotherapy were
      eligible. Chemotherapy was administered in a dose-escalated fashion in subgroups
      of 3-6 patients until dose-limiting toxicity (DLT) was encountered as follows:
      CPT-11 150 or 180 mg/m(2) followed by GEM 1,200-1,800 mg/m(2), both on days 1 +
      15, recycled every 28 days in four dose levels (DLs). RESULTS: Forty-nine
      patients entered the phase I and II part of the study (phase I: 12-phase II: 37 +
      3 at DL-3), and 40 patients were evaluable for a response in phase II and all for
      toxicity: median age, 61 years (range 36-74); PS, 1 (0-2); gender, 43 males/6
      females-histologies; adenocarcinoma, 25; squamous, 20; large cell, 4. Metastatic
      sites included lymph nodes, 38; bone, 5; liver, 4; brain, 3; lung nodules, 14;
      adrenals, 13; other, 3. All patients had prior taxane + platinum-based treatment,
      and 42 patients had prior docetaxel-ifosfamide-cisplatin/or-carboplatin regimens.
      DLT was observed at DL-4 and included 2/3 cases with grade 3 diarrhea-1/3 of
      these with febrile neutropenia. The recommended DL for phase II evaluation was
      DL3: GEM, 1,500 + CPT-11-180 mg/m(2). Objective responses in phase II were PR,
      6/40 [15%; 95% confidence interval (CI), 5-31%]; stable disease, 16/40 (40%; 95%
      CI, 21-53%); and progressive disease, 18/40 (45%; 95% CI, 28.5-62.5%). The median
      time-to-progression was 4 months (range 1-12) and median survival 7 months (range
      1.5-42 +), while 1-year survival was 20%. Grade 3/4 neutropenia was seen in 18%
      of patients (6% grade 4) and 6% incidence of febrile neutropenia. No Grade 3/4
      thrombocytopenia were seen, grade 3 diarrhea in 6% of patients and grade 2 in 15%
      of patients, while other grade 3 non-hematologic toxicities were never
      encountered. CONCLUSIONS: Bi-weekly GEM + CPT-11 is active and well tolerated in
      patients with advanced NSCLC failing prior taxane + platinum regimens, and
      represents an effective and convenient combination to apply in the palliative
      treatment of relapsed NSCLC particularly after failure of first-line docetaxel +
      platinum-based regimens.

PMID- 16622692
TI  - Robotic urologic surgery: is this the way of the future?

PMID- 16622693
TI  - [Solitary fibrous tumor in the tongue: case report and review of the literature].
AB  - Solitary fibrous tumors (SFT) are rare, mostly fibroblastic tumors usually
      situated in the pleura. Extrapleural manifestations have been described. However,
      the oral cavity is an uncommon localisation of this tumor. We report the very
      unusual case of an SFT affecting the tongue that could be removed completely
      because of its clear delineation. Intraoperative incisional biopsies were used to
      exclude malignancy. For definitive classification of the tumor, additional
      histopathologic examinations had to be carried out. Because SFT exhibit malignant
      behavior only in exceptional cases and their recurrence after complete removal
      has never been encountered, surgery can focus on the preservation of undisturbed
      function of the tongue.

PMID- 16622694
TI  - [Quality management: reduced waiting time and enhanced efficiency in a university
      ear, nose, and throat outpatient department].
AB  - BACKGROUND: The introduction of Diagnosis-Related Groups, which standardize
      payment for each clinical service, entails keeping the inpatient treatment as
      short as possible. Thus outpatient treatment is gaining in importance. To cope
      with this change, organizational and structural modifications of clinic routine
      are necessary. METHODS: In the ear, nose, and throat outpatient clinic of Johann
      Wolfgang Goethe University in Frankfurt, Germany, a hotline was established that
      allows patients to make appointments and get advice based on quality management
      guidelines according to DIN EN ISO 9001:2000. The development of this project is
      described here step by step, from planning to inclusion in the daily clinic
      routine. RESULTS: Patient visits became more effective despite increasing demand.
      This resulted in high satisfaction of patients and clinic personnel alike.
      CONCLUSION: This model may contribute considerably to coping with the increasing
      demand for clinic appointments and to optimal use of a clinic's human resources.

PMID- 16622695
TI  - [Fibrin gel for treatment of tympanic membrane perforations: an experimental
      animal model].
AB  - BACKGROUND: The goal of this study was to evaluate the effects of a fibrin gel on
      the healing of tympanic membrane perforation in rats. METHODS: Prolonged tympanic
      membrane perforations in 12 rats were created by application of mitomycin C to
      the intact tympanic membranes followed by bilateral myringotomy. Repeated
      applications of a fibrin gel to the perforation site of one tympanic membrane
      were performed in each animal. Tympanic membranes were observed for a total of 8
      weeks. RESULTS: One perforation in each group was already patent at the end of
      the observation period. The mean healing period of the remaining tympanic
      membranes was found to be 16.7 days in the fibrin gel group and 19.6 days in the
      control group. CONCLUSION: A fibrin sheet does not seem to promote the wound
      healing process of tympanic membranes. However, the sheet might serve as a drug
      delivery system for growth factors in the treatment of tympanic membrane
      perforations, because of its biocompatibility.

PMID- 16622696
TI  - Magnetic versus manual guidewire manipulation in neuroradiology: in vitro
      results.
AB  - INTRODUCTION: Standard microguidewires used in interventional neuroradiology have
      a predefined shape of the tip that cannot be changed while the guidewire is in
      the vessel. We evaluated a novel magnetic navigation system (MNS) that generates
      a magnetic field to control the deflection of a microguidewire that can be used
      to reshape the guidewire tip in vivo without removing the wire from the body,
      thereby potentially facilitating navigation along tortuous paths or multiple
      acute curves. METHOD: The MNS consists of two permanent magnets positioned on
      either side of the fluoroscopy table that create a constant precisely controlled
      magnetic field in the defined region of interest. This field enables
      omnidirectional rotation of a 0.014-inch magnetic microguidewire (MG). Speed of
      navigation, accuracy in a tortuous vessel anatomy and the potential for
      navigating into in vitro aneurysms were tested by four investigators with
      differing experience in neurointervention and compared to navigation with a
      standard, manually controlled microguidewire (SG). RESULTS: Navigation using MG
      was faster (P=0.0056) and more accurate (0.2 mistakes per trial vs. 2.6 mistakes
      per trial) only in less-experienced investigators. There were no statistically
      significant differences between the MG and the SG in the hands of experienced
      investigators. One aneurysm with an acute angulation from the carrier vessel
      could be navigated only with the MG while the SG failed, even after multiple
      reshaping manoeuvres. CONCLUSION: Our findings suggest that magnetic navigation
      seems to be easier, more accurate and faster in the hands of less-experienced
      investigators. We consider that the features of the MNS may improve the efficacy
      and safety of challenging neurointerventional procedures.

PMID- 16622697
TI  - Self-expanding stent-assisted middle cerebral artery recanalization: technical
      note.
AB  - INTRODUCTION: Investigation into pharmacological and mechanical means of
      improving recanalization rates by intraarterial therapy has led to technological
      development. Angiographic recanalization has been associated with improvement in
      clinical outcome. A clot retriever has recently joined an imperfect armamentarium
      for intraarterial stroke therapy. In this report, we describe successful
      recanalization of an acute thrombotic occlusion of the inferior division of the
      middle cerebral artery (MCA) achieved with a self-expanding stent. METHODS: An 82
      year-old woman with a history of coronary atherosclerosis and previous cerebellar
      hemorrhage presented with a National Institutes of Health Stroke Scale (NIHSS)
      score of 11. Perfusion computed tomography imaging showed a left MCA territory
      deficit. Diffusion-weighted magnetic resonance (MR) imaging revealed a small
      punctiform insular hyperintensity. Angiography documented occlusion of the
      inferior division of the left MCA (Thrombolysis in Myocardial Infarction or
      Thrombolysis in Cerebral Infarction, TIMI/TICI, grade 0). Intraarterial delivery
      of eptifibatide to the occlusion site failed to recanalize the vessel. Deployment
      of a self-expanding stent in the occluded segment resulted in complete
      revascularization of the distal vascular bed. RESULTS: Angiography performed on
      the next day confirmed patency of the stented vessel segment (TIMI/TICI 3). The
      patient was discharged 3 days after the procedure (NIHSS 3). MR angiography
      obtained 3 months after the procedure documented left MCA patency. CONCLUSION:
      This technique may have a role worthy of further investigation in acute stroke
      therapy.

PMID- 16622699
TI  - A review of the integrate-and-fire neuron model: I. Homogeneous synaptic input.
AB  - The integrate-and-fire neuron model is one of the most widely used models for
      analyzing the behavior of neural systems. It describes the membrane potential of
      a neuron in terms of the synaptic inputs and the injected current that it
      receives. An action potential (spike) is generated when the membrane potential
      reaches a threshold, but the actual changes associated with the membrane voltage
      and conductances driving the action potential do not form part of the model. The
      synaptic inputs to the neuron are considered to be stochastic and are described
      as a temporally homogeneous Poisson process. Methods and results for both current
      synapses and conductance synapses are examined in the diffusion approximation,
      where the individual contributions to the postsynaptic potential are small. The
      focus of this review is upon the mathematical techniques that give the time
      distribution of output spikes, namely stochastic differential equations and the
      Fokker-Planck equation. The integrate-and-fire neuron model has become
      established as a canonical model for the description of spiking neurons because
      it is capable of being analyzed mathematically while at the same time being
      sufficiently complex to capture many of the essential features of neural
      processing. A number of variations of the model are discussed, together with the
      relationship with the Hodgkin-Huxley neuron model and the comparison with
      electrophysiological data. A brief overview is given of two issues in neural
      information processing that the integrate-and-fire neuron model has contributed
      to - the irregular nature of spiking in cortical neurons and neural gain
      modulation.

PMID- 16622698
TI  - Intracranial angioplasty and stenting for cerebral atherosclerosis: new
      treatments for stroke are needed!
AB  - INTRODUCTION: Intracranial atherosclerosis is a common cause of stroke.
      INTRACRANIAL ANGIOPLASTY AND STENT REVASCULARIZATION: Recent technological
      developments offer improved methods for endovascular revascularization of
      symptomatic and asymptomatic cerebral artery stenosis. Identification of
      appropriate patients remains a diagnostic challenge, and our knowledge about the
      natural history of the disease remains limited. RECOMMENDATIONS: At this time,
      patients with significant intracranial stenosis should receive counseling on the
      benefits and risks of revascularization therapy. Ultimately, determination of
      which patients should undergo revascularization procedures will require carefully
      planned, randomized clinical trials.

PMID- 16622700
TI  - Transcriptome analysis of Aspergillus fumigatus exposed to voriconazole.
AB  - For a comprehensive evaluation of genes that have their expression modulated
      during exposure of the mycelia to voriconazole, we performed a large-scale
      analysis of gene expression in Aspergillus fumigatus using a microarray
      hybridization approach. By comparing the expression of genes between the
      reference time and after addition of voriconazole (30, 60, 120, and 240 min), we
      identified 2,271 genes differentially expressed in the wild-type strain. To
      validate the expression of some of these genes during exposure to voriconazole,
      we analyzed 13 genes showing higher expression in the presence of voriconazole by
      real-time RT-PCR. Although the magnitudes of induction differed between the two
      experimental systems, in about 85% of the cases they were in good agreement with
      the microarray data. To our knowledge this is the first study of microarray
      hybridization analysis for a filamentous fungus exposed to an antifungal agent.
      In our study, we have observed: (i) a decreased mRNA expression of various
      ergosterol biosynthesis genes; (ii) increased mRNA levels of genes involved in a
      variety of cell functions, such as transporters, transcription factors, proteins
      involved in cell metabolism, and hypothetical proteins; and (iii) the involvement
      of the cyclic AMP-protein kinase signaling pathway in the increased mRNA
      expression of several of these genes.

PMID- 16622701
TI  - Orthologs and paralogs of regA, a master cell-type regulatory gene in Volvox
      carteri.
AB  - The multicellular green alga Volvox carteri forma nagariensis has only two cell
      types: terminally differentiated somatic cells and reproductive cells. The regA
      gene maintains the terminally differentiated state of the somatic cells,
      apparently by repressing transcription of genes required for chloroplast
      biogenesis and thereby preventing cell growth. Because the RegA protein sequence
      bore no obvious motifs, we are attempting to identify regions of functional
      importance by searching for strongly conserved domains in RegA orthologs. Here we
      report the cloning and characterization of regA from the most closely related
      known taxon, V. carteri f. kawasakiensis. Given the closeness of the relationship
      between these two formas, their regA genes are surprisingly different: they
      differ in the number of introns and by several lengthy indels, and they encode
      proteins that are only 80% identical. We also serendipitously discovered a
      paralogous gene immediately upstream of each regA locus. The two regA genes, both
      upstream paralogs and several genes in Chlamydomonas (the closest unicellular
      relative of Volvox) encode a conserved region (the VARL domain) that contains
      what appears to be a DNA-binding SAND domain. This discovery has opened up a new
      avenue for exploring how regA and the terminally differentiated state that it
      controls evolved.

PMID- 16622702
TI  - The role of working memory in carrying and borrowing.
AB  - The present study analyzed the role of phonological and executive components of
      working memory in the borrow operation in complex subtractions (Experiments 1 and
      2) and in the carry operation in complex multiplications (Experiments 3 and 4).
      The number of carry and borrow operations as well as the value of the carry were
      manipulated. Results indicated that both the number of carry/borrow operations
      and the value of the carry increased problem difficulty, resulting in higher
      reliance on phonological and executive working-memory components. Present results
      are compared with those obtained for the carry operation in complex addition and
      are further discussed in the broader framework of working-memory functions.

PMID- 16622703
TI  - Single skeletal muscle fiber behavior after a quick stretch in young and older
      men: a possible explanation of the relative preservation of eccentric force in
      old age.
AB  - The origins of the smaller age-related decrease in eccentric force compared to
      isometric and concentric conditions in vivo remain unclear. Could this originate
      from contractile elements of muscle cells? The main intent of the current
      investigation was to assess the force behavior of muscle cells with aging, during
      lengthening. Chemically skinned single muscle fibers (n=235) from m. vastus
      lateralis of six young (mean age 31.6 years) and six older men (mean age 66.1
      years) were maximally activated with pCa 4.5 at 15 degrees C. Maximal isometric
      force and cross-sectional area were measured allowing the calculation of the
      tension (T (0)). A quick stretch (2 nm per half-sarcomere length) was applied and
      caused an immediate increase in tension followed by a decrease and a secondary
      delayed and transient rise in tension (phase 3); finally, the tension recovered a
      steady state value (phase 4). The tension enhancements during phase 3 (DeltaT
      (3)) and phase 4 (DeltaT (4)) were evaluated. The myosin heavy-chain isoform
      composition of each single fiber was determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. DeltaT (3) and DeltaT (4) were preserved in
      older men for both type I and IIa fibers despite a reduction in T (0). Therefore,
      the age-related preservation of the tension increments after a quick stretch in
      single muscle fibers could explain in part the smaller decrease in force during
      eccentric contractions compared to isometric and concentric conditions in vivo
      with aging usually observed.

PMID- 16622705
TI  - [Osteoid osteoma. CT guided drilling and radiofrequency ablation].
AB  - BACKGROUND: The CT-guided therapy of osteoid osteoma instead of older methods
      such as open resection has the advantage of exact localization of the nidus
      intraoperatively and exact documentation of its ablation. Another advantage is
      the less invasive approach. PATIENTS AND METHODS: A total of 52 patients with
      osteoid osteoma were treated in our institution between 1996 and 2005 either by
      radiofrequency ablation (n=11) or by percutaneous resection under CT guidance
      (n=41). Their age was between 7 and 48 years, mean age was 22.3 years, and follow
      up was 31.3 months. RESULTS: In all patients (n=52) the osteoid osteoma was
      successfully treated. In 50 patients the first treatment resulted in long-term
      success. In two patients the nidus was first missed; they were successfully
      treated with another operation using the same technique. CONCLUSION: The CT
      guided operation of osteoid osteoma made the therapy much easier because of the
      exact localization and the less invasive approach. This technique can be used
      analogously to tumor biopsy. The advantage is the exact documentation of the
      biopsy path and the possibility to take specimens.

PMID- 16622704
TI  - Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein).
AB  - Like several other ATP-binding cassette (ABC) transporters, ABCB4 is a lipid
      translocator. It translocates phosphatidylcholine (PC) from the inner to the
      outer leaflet of the canalicular membrane of the hepatocyte. Its function is
      quite crucial as evidenced by a severe liver disease, progressive familial
      intrahepatic cholestasis type 3, which develops in persons with ABCB4 deficiency.
      Translocation of PC makes the phospholipid available for extraction into the
      canalicular lumen by bile salts. The primary function of biliary phospholipid
      excretion is to protect the membranes of cells facing the biliary tree against
      these bile salts: the uptake of PC in bile salt micelles reduces the detergent
      activity of these micelles. In this review, we will discuss the functional
      aspects of ABCB4 and the regulation of its expression. Furthermore, we will
      describe the clinical and biochemical consequences of complete and partial
      deficiency of ABCB4 function.

PMID- 16622706
TI  - [Radiation protection in orthopaedics: implications for clinical practice of the
      new regulations governing roentgen ray irradiation and radioprotection].
AB  - In 2001 or 2002, the legislator made substantial alterations to the
      "Rontgenverordnung" [regulations governing use of roentgen ray radiation] and
      "Strahlenschutzverordnung" [regulations governing radiation protection]. This was
      done to bring German law in line with EU Directives 96/29/Euratom (basic safety
      standards for the protection of the health of workers and the general public
      against the dangers arising from ionizing radiation) and 97/43/Euratom (health
      protection of individuals against the dangers of ionizing radiation in relation
      to medical exposure). Proper use of radiation in medicine requires that those
      involved in its application are aware of the biological effects of radiation.
      When staff and others are protected good organization and appropriate technology
      at the workplace can achieve a great deal. In the new directives, the radiation
      protection for the patient is quantified and the responsibility of the physician
      is clearly pointed out. The most important aim is uniform quality throughout
      Europe in radiological diagnosis and radiation protection.

PMID- 16622707
TI  - Comprehensive expression profiling of the pectin methylesterase gene family
      during silique development in Arabidopsis thaliana.
AB  - Pectin methylesterases (PME, EC. 3.1.1.11) are enzymes that demethylesterify
      plant cell wall pectins in muro. In Arabidopsis thaliana, putative PME proteins
      are thought to be encoded by a 66-member gene family. This study used real-time
      RT-PCR to gain an overview of the expression of the entire family at eight
      silique developmental stages, in flower buds and in vegetative tissue in the
      Arabidopsis. Only 15% of the PMEs were not expressed at any of the developmental
      stages studied. Among expressed PMEs, expression data could be clustered into
      five distinct groups: 19 PMEs highly or uniquely expressed in floral buds, 4 PMEs
      uniquely expressed at mid-silique developmental stages, 16 PMEs highly or
      uniquely expressed in silique at late developmental stages, 16 PMEs mostly
      ubiquitously expressed, and 1 PME with a specific expression pattern, i.e. not
      expressed during early silique development. Comparison of expression and
      phylogenetic profiles showed that, within phylogenetic group 2, all but one PME
      belong to the floral bud expression group. Similar results were shown for a
      subset of one of the phylogenetic group, which differed from others by containing
      most of the PMEs that do not possess any PRO part next to their catalytic part.
      Expression data were confirmed by two promoter:GUS transgenic plant analysis
      revealing a PME expressed in pollen and one in young seeds. Our results highlight
      the high diversity of PME expression profiles. They are discussed with regard to
      the role of PMEs in fruit development and cell growth.

PMID- 16622709
TI  - Identification of three histone methyltransferases in Drosophila: dG9a is a
      suppressor of PEV and is required for gene silencing.
AB  - Organization of chromatin structure and regulation of gene transcription are
      contingent on histone tail modifications. Regions of the genome packaged with
      nucleosomes that contain methyl histone H3 at lysine 9 (Me K9H3) strongly
      correlate with regions that are silenced for transcription. To date Su(var)3-9 is
      the only K9H3 specific enzyme characterized in Drosophila melanogaster. In this
      study, we describe the identification of three additional Drosophila genes that
      potentially encode K9H3 specific methyltransferases (HMTase) with homology to
      known mammalian proteins. By several criteria, including sequence alignments,
      phylogenic analyses, and enzyme activity of the protein, one of these is a
      homologue of the human G9a and hence, we name it dG9a. dG9a catalyzes the
      transfer of methyl groups to full-length histone H3 and to N-terminal H3 peptides
      that contain lysine 9, suggesting that the major target for dG9a is K9H3.
      Chromatin extracts prepared from a P-element insert mutation in dG9a display an
      altered K9H3 methylation profile. In addition, the dG9a mutant is a dominant
      suppressor of position-effect variegation (PEV), a heterochromatin-associated
      gene silencing phenomenon. Su(var)3-9 also suppresses PEV. The combined Su(var)3
      9 and dG9a mutations have severe developmental defects suggesting an overlapping
      role for dG9a and Su(var)3-9 in the packaging of heterochromatin and gene
      silencing via a K9H3 methylation pathway.

PMID- 16622710
TI  - Assessment of errors caused by X-ray scatter and use of contrast medium when
      using CT-based attenuation correction in PET.
AB  - PURPOSE: Quantitative image reconstruction in positron emission tomography (PET)
      requires an accurate attenuation map of the object under study for the purpose of
      attenuation correction. Current dual-modality PET/CT systems offer significant
      advantages over stand-alone PET, including decreased overall scanning time and
      increased accuracy in lesion localisation and detectability. However, the
      contamination of CT data with scattered radiation and misclassification of
      contrast medium with high-density bone in CT-based attenuation correction (CTAC)
      are known to generate artefacts in the attenuation map and thus the resulting PET
      images. The purpose of this work was to quantitatively measure the impact of
      scattered radiation and contrast medium on the accuracy of CTAC. METHODS: Our
      recently developed MCNP4C-based Monte Carlo X-ray CT simulator for modelling both
      fan- and cone-beam CT scanners and the Eidolon dedicated 3D PET Monte Carlo
      simulator were used to generate realigned PET/CT data sets. The impact of X-ray
      scattered radiation on the accuracy of CTAC was investigated through simulation
      of a uniform cylindrical water phantom for both a commercial fan-beam multi-slice
      and a prototype cone-beam flat panel detector-based CT scanner. The influence of
      contrast medium was studied by simulation of a cylindrical phantom containing
      different concentrations of contrast medium. Moreover, an experimental study
      using an anthropomorphic striatal phantom was conducted for quantitative
      evaluation of errors arising from the presence of contrast medium by calculating
      the apparent recovery coefficient (ARC) in the presence of different
      concentrations of contrast medium. RESULTS: The analysis of attenuation
      correction factors (ACFs) for the simulated cylindrical water phantom in both fan
      and cone-beam CT scanners showed that the contamination of CT data with
      scattered radiation in the absence of scatter removal causes underestimation of
      the true ACFs, namely by 7.3% and 28.2% in the centre for the two geometries,
      respectively. The ARC was 190.7% for a cylindrical volume of interest located in
      the main chamber of the striatal phantom containing contrast medium corresponding
      to 2,000 Hounsfield units, whereas the ARC was overestimated by less than 5% for
      the main chamber and by approximately 2% for the left/right putamen and caudate
      nucleus compared with the absence of contrast medium. CONCLUSION: Without X-ray
      scatter compensation, the visual artefacts and quantitative errors in flat panel
      detector-based cone-beam geometry are substantial and propagate cupping artefacts
      to PET images during CTAC. Likewise, contrast-enhanced CT images may create
      considerable artefacts during CTAC in regions containing high concentrations of
      contrast medium.

PMID- 16622708
TI  - Sciatica in the female patient: anatomical considerations, aetiology and review
      of the literature.
AB  - The principal author was confronted few years ago with the case of a 38-year-old
      woman with a 5-month history of ill-defined L5 sciatic pain that was referred to
      an orthopaedic department for investigation and eventual surgical treatment for
      what was suspected to be herniated disc-related sciatica. Removal of her enlarged
      uterus found unexpectedly close to the sacroiliac joint upon lumbar MRI abolished
      her symptoms. Review of the literature showed that the lumbosacral trunk is
      vulnerable to pressure from any abdominal mass originating from the uterus and
      the ovaries. Physiological processes in the female patient and gynaecological
      diseases may be the source of sciatica, often not readily searched for, leading
      to fruitless investigations and surgical treatments. The aim of the paper is to
      highlight gynaecological and obstetrical causes of sciatica and sciatica-like
      symptoms. To prevent unproductive expenses and morbidity, a thorough
      gynaecological examination should be done even though neurological examination
      may be suggestive of a herniated intervertebral disc, and the cyclic pattern of
      pain related to menses should be routinely asked for.

PMID- 16622711
TI  - Advantages and pitfalls of 18F-fluoro-2-deoxy-D-glucose positron emission
      tomography in detecting locally residual or recurrent nasopharyngeal carcinoma:
      comparison with magnetic resonance imaging.
AB  - INTRODUCTION: This prospective study was designed to elucidate the advantages and
      pitfalls of (18)F-FDG PET in detecting locally residual/recurrent nasopharyngeal
      carcinoma (NPC) in comparison with MRI. METHODS: We recruited NPC patients from
      two ongoing prospective trials. One is being performed to evaluate suspected
      local recurrence (group A) and the other to assess local treatment response 3
      months after therapy (group B). Both groups received (18)F-FDG PET and head and
      neck MRI. The gold standard was histopathology or clinical/imaging follow-up. An
      optimal cut-off standardised uptake value (SUV) was retrospectively determined.
      RESULTS: From January 2002 to August 2004, 146 patients were eligible. Thirty
      four were from group A and 112 from group B. In all, 26 had locally
      recurrent/residual tumours. Differences in detection rate between (18)F-FDG PET
      and MRI were not statistically significant in either group. However, (18)F-FDG
      PET showed significantly higher specificity than MRI in detecting residual
      tumours among patients with initial T4 disease (p=0.04). In contrast, the
      specificity of (18)F-FDG PET for patients with an initial T1-2 tumour treated
      with intracavitary brachytherapy (ICBT) was significantly lower than that for
      patients not treated by ICBT (72.2% vs 98.1%, p=0.003). At an SUV cut-off of 4.2,
      PET showed an equal and a higher accuracy compared with MRI in groups A and B,
      respectively. CONCLUSION: (18)F-FDG PET is superior to MRI in identifying locally
      residual NPC among patients with initial T4 disease but demonstrates limitations
      in assessing treatment response in patients with initial T1-2 disease after ICBT.
      A cut-off SUV is a useful index for aiding in the visual detection of locally
      residual/recurrent NPC.

PMID- 16622712
TI  - [Stem cell therapy].

PMID- 16622714
TI  - Medication errors and patient complications with continuous renal replacement
      therapy.
AB  - Continuous renal replacement therapy (CRRT) is commonly used for renal support in
      the intensive care unit. While the risk of medication errors in the intensive
      care unit has been described, errors related specifically to CRRT are unknown.
      The purpose of this study is to characterize medication errors related to CRRT
      and compare medication errors that occur with manually compounded solutions
      versus commercially available solutions. We surveyed three separate internet
      based, pediatric list serves that are commonly used for communications for
      programs utilizing CRRT. Data regarding CRRT practices and medication errors were
      recorded. Medication errors were graded for degree of severity and compared
      between programs using manually compounded dialysis solutions versus commercially
      available dialysis solutions. In a survey with 31 program responses, 18 reported
      medication errors. Two of the 18 were related to heparin compounding, while 16/18
      were due to solution compounding errors. Half of the medication errors were
      classified as causing harm, two of which were fatal. All medication errors were
      reported by programs that manually compounded their dialysis solutions.
      Medication errors related to CRRT are associated with a high degree of severity,
      including death. Industry-based, commercially available solutions can decrease
      the occurrence of medication errors due to CRRT.

PMID- 16622713
TI  - Suicidal death of erythrocytes in recurrent hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia with
      fragmented erythrocytes, thrombocytopenia, and acute renal failure. Lack of
      complement inactivating factor H predisposes to the development of atypical HUS.
      Little is known about mechanisms linking complement activation with loss of
      erythrocyte integrity during HUS. Recent studies disclosed that increased
      cytosolic Ca2+ activity and cellular ceramide trigger programmed erythrocyte
      death or eryptosis, characterized by cell shrinkage and phosphatidylserine
      exposure at the erythrocyte surface. In the present study, we investigated
      whether eryptosis occurs during the course of HUS. To this end, erythrocytes from
      healthy volunteers were exposed to plasma from a patient with severe idiopathic
      recurrent HUS secondary to factor H depletion. Phosphatidylserine exposure
      (Annexin binding), cell volume (forward scatter), cytosolic Ca2+ activity (Fluo3
      fluorescence), and ceramide formation [anti-ceramide antibody and enzymatic
      (diacylgycerol kinase) analysis] were determined. Exposure of erythrocytes to
      plasma from the patient, but not to plasma from healthy individuals, triggered
      Annexin binding. The effect of plasma on erythrocyte Annexin binding was
      abolished by plasmapheresis or filtration at 30 kDa. It was paralleled by
      formation of ceramide and increase of cytosolic Ca2+ activity. Enhanced Annexin
      binding of erythrocytes from healthy individuals was observed after exposure to
      plasma from three other patients with HUS. The proeryptotic effect of patient
      plasma was mimicked by exposure to the Ca2+ ionophore ionomycin, and eryptosis
      was potentiated in the presence of cell membrane-permeable C6-ceramide.
      Furthermore, in vitro complement activation similarly triggered erythrocyte
      phosphatidylserine exposure, an effect which was blunted by the addition of
      factor H. In conclusion, our present observations disclose a novel,
      pathophysiological, factor-H dependent mechanism leading to injury of
      erythrocytes during the course of hemolytic uremic syndrome.

PMID- 16622715
TI  - Immunohistochemical investigation of dopaminergic terminal markers and caspase-3
      activation in the striatum of human methamphetamine users.
AB  - Methamphetamine (METH) has been shown to induce neurotoxicity. In a previous
      human study using quantitative Western blotting and radioligand binding assay,
      dopaminergic terminal marker deficits were induced in chronic METH users. In this
      study, we examined the suitability of the immunohistochemical detection of
      tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine
      transporter-2 (VMAT2) levels, and caspase-3 activation in the striatum to
      diagnose METH abuse. Decreases in TH immunoreactivity in the nucleus accumbens
      and DAT in the nucleus accumbens and putamen were induced in METH users, whereas
      a significant difference of VMAT2 was not evident between METH and control
      groups. However, in the nucleus accumbens of two METH users, levels of VMAT2, a
      stable marker of striatal dopaminergic terminal integrity, were reduced
      remarkably. These findings might indicate that dopaminergic terminal degeneration
      is induced in the striatum of some METH abusers. On the other hand, we observed
      little caspase-3 activation, indicative of apoptosis, in the striatal neurons of
      chronic METH users. Overall, the findings of dopaminergic terminal markers were
      similar to those in the previous human study. Therefore, it is suggested that
      immunohistochemical techniques could be used to examine dopaminergic terminal
      marker levels and could also give useful information on chronic and/or lethal
      METH use in cases of METH-related death, where METH intoxication may not be
      toxicologically demonstrated.

PMID- 16622718
TI  - Lack of increase in postoperative complications with low-dose methotrexate
      therapy in patients with rheumatoid arthritis undergoing elective orthopedic
      surgery.
AB  - To determine the potential contribution of intermittent low-dose methotrexate
      (MTX) treatment (2-8 mg/week) to postoperative complications, we studied 122
      patients with rheumatoid arthritis (RA) who had 201 surgical procedures. The
      patients with treatment with MTX were allocated to two groups: those who
      continued MTX (group A, 77 procedures) and those who discontinued MTX more than 1
      week (group B, 21 procedures). The patients who had no treatment with MTX were
      allocated to group C (103 procedures). The incidence of postoperative infection,
      poor wound healing, and flare-up of RA was compared between the three groups.
      Postoperative infection occurred in 3.9%, 4.8%, and 3.9% in groups A, B, and C,
      respectively. Poor wound healing was experienced in 1.3%, 9.5%, and 7.8% in
      groups A, B, and C, respectively. At 4 weeks postoperatively, 3.9%, 14.3%, and
      6.8% of flares were seen in groups A, B, and C, respectively. No significant
      difference was found in the patients with or without perioperative use of MTX.
      From these results, it is unlikely that continuation of intermittent low-dose MTX
      treatment increases the risk of postoperative complications in patients with RA.
      Continued treatment with MTX during perioperative period could suppress disease
      flares, especially in severe RA patients.

PMID- 16622717
TI  - T-cell activation via CD26 and caveolin-1 in rheumatoid synovium.
AB  - CD26 is a T-cell costimulatory molecule with dipeptidyl peptidase IV (DPPIV)
      activity in its extracellular region. We previously reported that recombinant
      soluble CD26 enhances peripheral blood T-cell proliferation induced by the recall
      antigen tetanus toxoid (TT). Recently, we demonstrated that CD26 binds caveolin-1
      on antigen-presenting cell (APC), and that residues 201-211 of CD26 along with
      the serine catalytic site at residue 630, which constitute a pocket structure of
      CD26/DPPIV, contribute to binding to caveolin-1 scaffolding domain. In addition,
      following CD26-caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is
      phosphorylated, with linkage to NF-kappaB activation, followed by upregulation of
      CD86. Finally, reduced caveolin-1 expression on APC inhibits CD26-mediated CD86
      upregulation and abrogates CD26 effect on TT-induced T-cell proliferation, and
      immunohistochemical studies revealed an infiltration of CD26+ T cells in the sub
      lining region of rheumatoid synovium and high expression of caveolin-1 in the
      increased vasculature and synoviocytes of the rheumatoid synovium. Taken
      together, these results strongly suggest that CD26-cavolin-1 interaction plays a
      role in the upregulation of CD86 on TT-loaded APC and subsequent engagement with
      CD28 on T cells, leading to antigen-specific T-cell activation such as the T-cell
      mediated antigen-specific response in rheumatoid arthritis.

PMID- 16622719
TI  - Twenty-four-week follow-up examination of a leukocytapheresis therapy in
      rheumatoid arthritis.
AB  - Several clinical trials have demonstrated that leukocytapheresis (LCAP) is a safe
      and effective therapy for patients with refractory rheumatoid arthritis (RA).
      However, most of those reports were limited to short-term clinical observation.
      We have treated 11 RA patients with LCAP and observed them for 24 weeks after the
      final administration. The 11 cases included 3 diabetes patients, 2 patients with
      interstitial pneumonia, 1 patient with diffuse panbronchiolitis, and 1 patient
      with old pulmonary tuberculosis. Alternative therapies for all of these patients
      were considered difficult. Once-a-week LCAP administration was added for 5 weeks
      to the previous therapeutic regime in all patients, and the treatment efficacy
      was prospectively qualified. At 4 weeks after the final LCAP therapy, 8 of the 11
      patients (73%) had achieved an American College of Rheumatology (ACR) 20%
      response, and 3 of the 11 (27%) had achieved both ACR 50% and ACR 70% responses.
      Although the efficacy decreased after the observation periods, an ACR 20%
      response was maintained in 5 patients (45%) at 24 weeks. Although only a limited
      number of patients were examined in this study, the results suggested that LCAP
      therapy will be beneficial to RA patients, including patients who cannot be
      treated with tumor necrosis factor inhibitors or conventional disease-modifying
      antirheumatic drugs.

PMID- 16622720
TI  - Risk factors for knee osteoarthritis in Japanese men: a case-control study.
AB  - Risk of knee osteoarthritis (OA) was assessed in a population-based case-control
      study of Japanese men. The study covered three health districts in Wakayama and
      Osaka prefectures, Japan. Subjects were male individuals >or=45 years old
      diagnosed radiographically with knee OA, and who did not display any established
      causes of secondary OA. Controls selected randomly from the general population
      were individually matched to cases for age, sex, and residential district.
      Subjects were interviewed using structured questionnaires to determine medical
      history, physical activity, socio-economic factors, and occupation. Interviews
      were obtained from 37 cases and 37 controls. In univariate analysis, heaviest
      weight in the past and physical work such as factory, construction, agricultural,
      or fishery work as the principal occupation significantly raised the risk of male
      knee OA (P<0.05). Odds ratios (OR) were determined using conditional logistic
      regression analysis mutually adjusted for potential risk factors using the
      results of univariate analysis. Heaviest weight in the past (OR 6.01, 95%
      confidence interval (CI) 1.18-30.5, P<0.05), past knee injury (OR 6.25, 95% CI
      1.13-34.5, P<0.05), and physical work as the principal occupation (OR 6.20, 95%
      CI 1.40-27.5, P<0.05) represented independent factors associated with knee OA
      after controlling for other risk factors. Physical work is associated with knee
      OA, demonstrating the influence of working activity on the development of OA. The
      present study suggests that risk factors for knee OA in men resemble those in
      women.

PMID- 16622721
TI  - Adrenocorticotropic hormone and dehydroepiandrosterone sulfate levels of
      rheumatoid arthritis patients treated with glucocorticoids.
AB  - To assess adrenal function with respect to the presence or absence of steroid
      therapy, we investigated differences in the blood levels of adrenocorticotropic
      hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) in relation to steroid
      (prednisolone) administration in 123 patients with rheumatoid arthritis (RA).
      Levels of ACTH and DHEAS were significantly lower in the steroid-treated group
      than in the non-treated group (ACTH: 11.79 pg/ml vs 27.92 pg/ml) (DHEAS: 418.12
      ng/ml vs 883.91 ng/ml) (P<0.0001). We observed no steroid dose-related
      differences in ACTH levels. However, DHEAS levels showed a slight decrease at a
      prednisolone dose of 2.5 mg/day, with a significant decrease being observed at a
      dose of 5 mg/day when statistical adjustments were made for age and sex
      (P<0.0001). At doses of 7.5 mg/day or greater, DHEAS levels were significantly
      lower than those for 5 mg/day (P<0.0006). These results suggest that low-dose
      prednisolone reduces adrenal function in patients with RA. We recommend that
      doses of prednisolone should be limited to 5 mg/day or less in consideration of
      adrenal function when treating RA patients. The measurement of ACTH and DHEAS may
      be useful for evaluating adrenal function in patients with RA.

PMID- 16622722
TI  - Pneumocystis jiroveci pneumonia associated with low-dose methotrexate treatment
      for rheumatoid arthritis: report of two cases and review of the literature.
AB  - Low-dose methotrexate (MTX) therapy is widely used for rheumatoid arthritis (RA)
      because of its favorable efficacy and toxicity profile. Although Pneumocystis
      jiroveci pneumonia (PCP) is most often seen in severely immunosuppressed
      patients, PCP complicating low-dose MTX therapy for RA has been reported to
      sometimes occur. We herein report two cases of patients who developed PCP during
      treatment with low-dose MTX, and discuss the importance of prophylaxis for this
      opportunistic infection.

PMID- 16622723
TI  - A case of interstitial pneumonia caused by bucillamine: a study using serological
      markers.
AB  - The patient was a 61-year-old man diagnosed with rheumatoid arthritis (RA) in
      2001. He initially received treatment at a nearby clinic, but his condition could
      not be satisfactorily controlled. He subsequently consulted our hospital during
      the same year. Although his symptoms improved in response to treatment at our
      hospital, slight fever, cough, and then high fever and dyspnea subsequently
      developed. A diagnosis of interstitial pneumonia was made on the basis of
      findings of diagnostic imaging. The time course of changes in serological
      markers, including surfactant protein A (SP-A), surfactant protein D (SP-D), and
      KL-6, as well as markers of inflammatory reaction and lactate dehydrogenase was
      examined to determine the clinical significance of serological markers in the
      management of interstitial pneumonia.

PMID- 16622724
TI  - Recurrent paralytic ileus associated with strongyloidiasis in a patient with
      systemic lupus erythematosus.
AB  - We present an interesting case of recurrent paralytic ileus due to
      strongyloidiasis in a woman who was being treated with corticosteroids and
      immunosuppressants for systemic lupus erythematosus (SLE). She was also a carrier
      of human T-cell leukemia virus type I. She had a history of strongyloidiasis 8
      years earlier. Recurrent episodes of paralytic ileus due to strongyloidiasis
      occurred during treatment of her SLE with corticosteroids. Ivermectin was given
      and improved the symptoms. This case shows that symptomatic strongyloidiasis can
      be induced in immunocompromised hosts by immunosuppressive therapy. It is
      important to rule out strongyloidiasis prior to starting immunosuppressive
      therapy in patients from endemic areas.

PMID- 16622725
TI  - Hypokalemic paralysis and osteomalacia secondary to renal tubular acidosis in a
      case with primary Sjogren's syndrome.
AB  - A 39-year-old Japanese woman was admitted to our hospital for severe weakness
      owing to potassium deficiency caused by type 1 renal tubular acidosis (RTA1).
      Sicca complex, serological tests, and lip biopsy revealed that she had Sjogren's
      syndrome (SS). Acidosis was corrected by alkali supplement treatment. She also
      had an impaired renal function with proteinuria, and high absorbance on Ga
      scintigram was recognized in both kidneys. She was taking warfarin potassium
      after aortic valve substitution due to aortic regurgitation, therefore renal
      biopsy was not performed. Prednisone (20 mg/day) was administered for renal
      inflammation. One month later, she suffered severe chest wall pains with some
      local tender points over the costae of both sides, which was presumed to be due
      to pseudo-fractures based on osteomalacia. Hypokalemic paralysis and osteomalacia
      should be taken into consideration in the diagnosis of SS with RTA1.

PMID- 16622726
TI  - Enlarged psoas muscle and iliopsoas bursitis associated with a rapidly
      destructive hip in a patient with rheumatoid arthritis.
AB  - A 39-year-old man with rheumatoid arthritis developed femoral neuropathy
      secondary to iliopsoas bursitis. The adjacent hip joint was severely damaged.
      Magnetic resonance imaging showed enlargement and inflammation of the psoas
      muscle at the same side of iliopsoas bursitis. Iliopsoas bursitis and abnormal
      findings of the psoas muscle disappeared while the symptoms improved.

PMID- 16622727
TI  - A case of polymyositis complicated with interstitial pneumonitis and
      pneumomediastinum.
AB  - Pneumomediastinum as a complication of interstitial pneumonia with leakage of air
      into the mediastinum or subcutaneous tissues is a rare complication of
      dermatomyositis (DM). Herein we report a case of pneumomediastinum complicating
      polymyositis (PM), which is usually associated with DM. A 61-year-old man was
      hospitalized in our department because of deterioration of interstitial
      pneumonia. Treatment with high-dose corticosteroid and cyclosporin A steadily
      improved his interstitial pneumonia. Two weeks later, he developed subcutaneous
      emphysema and chest X-ray showed pneumomediastinum. Both subcutaneous emphysema
      and pneumomediastinum improved gradually without any additional treatment.

PMID- 16622728
TI  - Pneumocystis jiroveci pneumonia in a patient with rheumatoid arthritis as a
      complication of treatment with infliximab, anti-tumor necrosis factor alpha
      neutralizing antibody.
AB  - We report that a-63-year-old woman developed Pneumocystis jiroveci pneumonia
      (PCP) as a complication from treatment with infliximab for rheumatoid arthritis.
      Although there was neither symptoms of dyspnea nor typical observations on a
      chest X-ray examination, low levels of oxygen saturation and findings of high
      resolution chest computed tomographic scanning suggested a possibility of
      interstitial pneumonia. A polymerase chain reaction-based detection of
      Pneumocystis jiroveci in induced sputum allowed an early diagnosis of PCP and
      subsequent effective treatment.

PMID- 16622730
TI  - Prevalence and clinical features of Paget's disease of bone in Japan.
AB  - The present study aimed to evaluate the prevalence and clinical presentation of
      Paget's disease of bone (PDB) in Japan. As PDB is a very rare disease in Japan, a
      nationwide mail survey was conducted targeting doctors in the specialty most
      frequently diagnosing and treating PDB patients in Japan. First, the literature
      for all case reports in Japan published between January 1990 and December 2002
      was reviewed to determine who was diagnosing and treating PDB in Japan. This
      literature review for all case reports in Japan revealed that 72.1% of cases in
      Japan were reported from departments of orthopedic surgery. A nationwide two
      phase mail survey was conducted for the departments of orthopedic surgery of
      2,320 general hospitals accredited by the Japanese Orthopaedic Association. Phase
      1 involved determining how many patients with PDB were followed at each hospital.
      If the answer was one or more, phase 2 of the survey gathered information on the
      clinical presentation of current patients. The mail survey yielded a final
      response rate of 75.4% for phase 1 and 87.6% for phase 2. Phase 1 indicated that
      the prevalence of PDB in Japan is about 2.8 cases per million capita. Phase 2
      revealed a slight female predominance, lower frequency of familial clustering,
      higher frequency of femoral fracture in the affected femur, and a higher ratio of
      symptomatic PDB in Japan compared with findings in countries displaying a higher
      prevalence of PDB. The present epidemiological study revealed that the disorder
      is extremely rare in Japanese individuals, and that some differences exist with
      regard to the clinical features of PDB between Japanese patients and patients
      from high-prevalence countries.

PMID- 16622731
TI  - Involvement of Notch signaling in initiation of prechondrogenic condensation and
      nodule formation in limb bud micromass cultures.
AB  - Notch signaling is an evolutionarily conserved mechanism that plays a critical
      role in the determination of multiple cellular differentiation pathways and
      morphogenesis during embryogenesis. The limb bud high-density culture is an
      established model that recapitulates mesenchymal condensation and chondrocyte
      differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) showed
      that Notch and its related genes were expressed in such cultures on day 1 and
      reached a peak between day 3 and day 5, when cell condensation and nodule
      formation were initiated. Immunohistochemical experiments revealed that the
      expression of Notch1 was initially localized within the nodules and shifted to
      their peripheral region as the cell differentiation progressed. We disrupted
      Notch signaling by using a gamma-secretase inhibitor, N-[N-(3,5
      difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), to analyze
      the function of Notch signaling in the culture system. The blocking of Notch
      signaling by DAPT apparently promoted the initiation of prechondrogenic
      condensation and fusion of the nodules, and such an effect was reversed by
      exogenous expression of the Notch cytoplasmic domain. DAPT treatment also induced
      chondrogenic markers and bone morphogenetic protein (BMP)-related molecules,
      including type II collagen, Sox9, GDF5, and Id1. These observations imply that
      the Notch signal may have an important role in chondrogenic differentiation by
      negatively regulating the initiation of prechondrogenic condensation and nodule
      formation.

PMID- 16622732
TI  - High-turnover osteoporosis is induced by cyclosporin A in rats.
AB  - Cyclosporin A (CsA) is used widely as an immunosuppressive agent, but it induces
      osteoporosis as a prominent side effect. To elucidate the mechanisms involved in
      CsA-induced osteoporosis, the effects of CsA on bone metabolism were investigated
      in a rat experimental model. Fifteen-day-old rats were fed a powdered diet
      containing or lacking CsA for 8-30 days. Analysis was performed by micro-computed
      tomography (muCT) and light microscopy to examine histomorphometric changes in
      rat tibiae on days 8, 16, and 30. Plasma parathyroid hormone (PTH) and
      osteocalcin (OCN) levels were determined by enzyme-linked immunosorbent assay
      (ELISA) on days 8, 16, and 30. The expression of OCN, osteopontin (OPN), and
      cathepsin K mRNAs in tibial bone marrow was examined by Northern blot analysis on
      days 8 and 16. Although no significant differences were observed in tibial length
      during the experimental periods, or in histomorphometric parameters on day 8, an
      apparent decrease in bone volume was observed in the CsA-treated group after day
      16. Histologic analysis showed that the number of osteoblasts and osteoclasts on
      the surface of trabecular bone in the CsA-treated group had increased
      significantly on day 16. Plasma PTH and OCN levels in CsA-treated rats were
      significantly higher than those in control animals on day 8. Northern blot
      analysis revealed that the CsA-treated group showed an increase in the expression
      of OCN, OPN, and cathepsin K mRNAs on day 8 compared with the controls. These
      findings suggest that bone resorption in CsA-treated rats is induced by high
      turnover osteoporosis and that bone remodeling activity may be activated by PTH.

PMID- 16622733
TI  - Combined intervention of dietary soybean proteins and swim training: effects on
      bone metabolism in ovariectomized rats.
AB  - Soybean proteins, a rich source of isoflavones, taken immediately after an
      ovariectomy prevent bone loss in rats. Exercise-induced stimuli are essential for
      bone growth. Few studies exist about the combined effects of swim training and
      soybean protein supplementation on bone metabolism. So, the purpose of this study
      was to investigate, in 48 female Sprague-Dawley rats (12 weeks old) the effects
      of an 8-week swim-training regimen (1 h/day, 5 days/week) and dietary soybean
      proteins (200 g/kg diet) on bone metabolism. Rats were randomly assigned to four
      groups: (1) ovariectomized fed with a semisynthetic control diet; (2)
      ovariectomized fed with a soybean protein-enriched semisynthetic diet; (3)
      ovariectomized trained to exercise and fed with control diet; (4) ovariectomized
      trained to exercise and fed with a soybean protein diet. Following the treatment
      period, body weight gain was identical in the four groups. Soybean protein
      supplementation increased bone calcium content, and reduced plasma osteocalcin
      values, without significant modification of calcium balance and net calcium
      absorption. Swim training enhanced plasma and bone calcium content and calcium
      balance and net calcium absorption. It did not modify either plasma osteocalcin
      values or urinary deoxypyridinoline excretion. Both exercise and soybean protein
      intake increased plasma on bone calcium without modifying net calcium absorption
      or bone markers. In conclusion, we demonstrated, in ovariectomized rats, that
      swimming exercise and dietary supplementation with soy proteins do not have
      synergistic effects on calcium metabolism and bone markers.

PMID- 16622734
TI  - The status of biochemical parameters in varying degrees of vitamin D deficiency.
AB  - Vitamin D (Vit D) is an essential element for the regulation of serum calcium,
      phosphate, and alkaline phosphatase (Alk Ph). Because the Vit D serum level is
      not usually measured directly, Vit D deficiency is diagnosed indirectly by
      changes in serum calcium, phosphate, and Alk Ph leves. The current study assessed
      the status of these biochemical parameters in subjects with different degrees of
      Vit D deficiency. We selected 1,210 subjects, between 20 and 69 years old,
      randomly from the Tehran population. Subjects with diseases or medications that
      modified bone metabolism were excluded from the study. Serum 25(OH) D, calcium,
      phosphate, Alk Ph, and parathyroid hormone (PTH) levels were measured and the
      status of these biochemical parameters was compared in subjects with different
      degrees of Vit D deficiency. Vit D deficiency was diagnosed in 79.6% of the
      subjects. Different degrees of Vit D deficiency were classified as follows: group
      1, severe; group 2, moderate; and group 3, mild. Serum PTH levels in the Vit D
      deficient groups were significantly higher than that in group 4 (normal Vit D).
      Serum calcium and phosphate levels in groups 1 and 2 were significantly lower
      than those in groups 3 and 4. No significant difference was seen in serum Alk Ph
      in the groups with different degrees of Vit D deficiency. The sensivity for at
      least one biochemical variable (calcium, phosphorus, or Alk Ph) for the detection
      of severe, moderate, and mild Vit D deficiency was 24.2%, 13.8%, and 6%,
      respectively. When the serum 25(OH) D level was reduced to less than 25 nmol/l
      (groups 1 and 2), the effects of Vit D deficiency on calcium and phosphate levels
      were obvious. Therefore, the usual biochemical parameters (calcium, phosphate,
      Alk Ph) alone do not have sufficient sensitivity to detect mild deficiency of Vit
      D.

PMID- 16622735
TI  - The sample size required for intervention studies on fracture prevention can be
      decreased by using a bone resorption marker in the inclusion criteria:
      prospective study of a subset of the Nagano Cohort, on behalf of the Adequate
      Treatment of Osteoporosis (A-TOP) Research Group.
AB  - In drug developments for osteoporosis, large-scale and longterm fracture
      prevention studies have been required. We investigated whether or not it was
      possible to reduce the sample size and observation period under new selection
      criteria for an osteoporotic fracture-prevention study. A Poisson regression
      model was used to identify independent risks for incident vertebral fracture in
      515 postmenopausal women who had had no intervention for osteoporosis; this group
      was a subset of Nagano Cohort participants. The total observation period for this
      group was 2,577 person-years, and a total of 146 new vertebral fractures were
      observed. Risk assessment for incident vertebral fracture among numerical
      covariates revealed that the following items showed significant independent risks
      for incident fractures; namely, baseline age (hazard ratio [HR]; 1.84; 95%
      confidence interval (CI), 1.44-2.35; P < 0.001), number of preexisting vertebral
      fractures (HR, 1.28; 95% CI, 1.17-1.40; P < 0.001), baseline lumbar bone mineral
      density (LBMD) (HR, 0.79; 95% CI, 0.71-0.88; P < 0.001), and urinary excretion of
      deoxypyridinoline (DPD) (HR, 1.18; 95% CI, 1.03-1.35; P = 0.016). Because the
      initial urinary excretion of DPD was found to be a risk for incident vertebral
      fracture, in addition to the conventional risks, we assessed whether or not the
      sample size or observation period could be reduced by the incorporation of the
      urinary excretion of DPD into the selection criteria of a fracture-prevention
      study. The assessment of sample size was calculated, using the log rank test, at
      a two-tailed significance level of 5% and with a power of 80%. When osteoporotic
      patients with preexisting fracture were selected (conventional criteria), the 3
      year probability of vertebral fracture was estimated as 14.3% in the present
      population. On the other hand, the new vertebral fracture rate during 3 years in
      the osteoporotic patients with preexisting fracture plus high urinary DPD (HR,
      above 1.0); (new selection criteria) was estimated as 23.2%. When the HR between
      test drug and placebo was changed from 0.4 to 0.8, the required sample size for
      any level of HR showed a 40% reduction for the new selection criteria compared to
      the conventional criteria. Therefore, the addition of urinary DPD level to the
      selection criteria is useful to reduce sample size in an osteoporosis fracture
      prevention study.

PMID- 16622736
TI  - Assessment of linkage and association of 13 genetic loci with bone mineral
      density.
AB  - Bone mineral density (BMD), an important risk factor for osteoporosis, is a
      complex trait likely affected by multiple genes. The linkage and/or association
      of 13 polymorphic loci of seven candidate genes (estrogen receptor alpha
      [ERalpha] and beta [ERbeta], calcium-sensing receptor, vitamin D receptor,
      collagen type 1alpha1, low-density lipoprotein [LDL] receptor-related protein 5
      [LRPS], and transforming growth factor beta1) were evaluated in 177 southern
      Chinese pedigrees of 674 subjects, with each pedigree identified through a
      proband having a BMD Z score of -1.28 or less at the hip or spine. A suggestive
      linkage was detected between the IVS1-351A/G polymorphism of ERalpha and spine
      BMD, and between the 1082G/A, 1730G/A, and D14S1026 polymorphisms of ERbeta and
      BMD at both spine and hip. The quantitative transmission disequilibrium test
      (QTDT) detected total family association between 1730G/A of ERbeta and BMD at
      spine and hip; between D14S1026 of ERbeta and hip BMD; and between the 266A/G and
      2220C/T polymorphisms of LRP5 and hip BMD. Similar total family associations were
      detected when only the females were analyzed. In addition, the IVS1-397T/C
      polymorphism of ERalpha was associated with spine BMD, and the 266A/G and 2220C/T
      polymorphisms of LRP5 were associated with femoral neck BMD in the females. A
      within-family association was detected with the IVS1-397T/C polymorphism of
      ERalpha, and the 266A/G and 2220C/T polymorphisms of LRP5 in the females. The
      effect of each polymorphism on BMD variance ranged from 1% to 4%. In conclusion,
      ERalpha, ERbeta and LRP5 are important candidate genes determining BMD variation,
      especially in females.

PMID- 16622737
TI  - Maternal and early life influences on calcaneal ultrasound parameters and
      metacarpal morphometry in 7- to 9-year-old children.
AB  - We investigated the relationship between maternal and early life influences,
      calcaneal ultrasound parameters, and metacarpal morphometry in 7- to 9-year-old
      children (n = 109) of mixed ancestral origin from a working class community.
      Their mothers had participated in a nutrition and pregnancy study at the time of
      the birth. Demographic and maternal data were collected. Anthropometry was
      assessed. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) were
      measured in the children and a subsample of the mothers (n = 94), using calcaneal
      ultrasound. Hand radiographs were used to measure metacarpal morphometry. There
      was no relationship between the ultrasound parameters, birthweight, current
      weight, or height. The ponderal index was correlated with BUA (r = 0.25; P =
      0.036). BUA was lower in children whose mothers smoked during pregnancy compared
      to children whose mothers did not smoke (P = 0.054). Children whose mothers
      consumed alcohol during pregnancy had a lower Barnett-Nordin metacarpal index
      compared to children whose mothers did not consume alcohol (P < 0.05), after
      covarying for sex, age, gestational age, weight, and height of the child.
      Children's BUA was negatively correlated with housing density (r = -0.23; P =
      0.021). In this study, we found an association between maternal and early life
      influences on calcaneal ultrasound parameters and metacarpal morphometry in
      prepubertal children, an association that was also influenced by sociodemographic
      and environmental factors.

PMID- 16622738
TI  - Tamoxifen flare hypercalcemia: an additional support for gallium nitrate usage.
AB  - In 12 of 93 hypercalcemic patients with metastatic advanced breast cancer treated
      with tamoxifen the most common life-threatening metabolic complication of flare
      hypercalcemia developed. All the hypercalcemic patients had osteolytic or mixed
      lytic and blastic bone metastases. In patients with advanced breast cancer,
      hypercalcemia develops within the first few weeks of initiation of tamoxifen
      therapy. In our study group, calcium levels were measured frequently in both
      serum and urine samples by a semi-autoanalyzer and an autoanalyzer, using
      standard methods. Elevation of calcium levels was noticed in the tamoxifen
      receiving hypercalcemic breast cancer patients, and levels returned to normal
      when tamoxifen was withdrawn. The median duration of flare hypercalcemia was 9
      days (range, 4-16 days). The median calcium value was 13.6 mg/dl (range, 11.7
      15.8). The diagnosis of tamoxifen flare hypercalcemia was based on the normal
      pretreatment serum or urine calcium values and the occurrence of hypercalcemia
      within the first few weeks of tamoxifen initiation. There are no specific
      treatment recommendations for hormone flare hypercalcemia, except for tamoxifen
      withdrawal, which is usually temporary, and the introduction of a low dose of an
      antihypercalcemic drug. We evaluated the effect of such a drug, gallium nitrate,
      on flare hypercalcemia. All the patients were treated with hydration, and 6
      patients, whose calcium level was above 13.6 mg/dl, were treated with a moderate
      dose of gallium nitrate (200 mg/m(2) per kg) for 5 consecutive days, they
      achieved normocalcemia and continued with tamoxifen. The median time from
      hormonal drug initiation to flare hypercalcemia was 17.5 days, and median
      duration was 9 days. The above result indicates that the serious metabolic
      complication of hypercalcemia develops due to the iatrogenic effect of tamoxifen,
      but it can be controlled with an antihypercalcemic drug, gallium nitrate, while
      continuing tamoxifen therapy. It seems that the use of gallium nitrate in the
      treatment of flare hypercalcemia could allow safe readministration of tamoxifen
      and prevent premature tamoxifen discontinuance or withdrawal.

PMID- 16622739
TI  - Bovine deciduous dentine is more susceptible to osteoclastic resorption than
      permanent dentine: results of quantitative analyses.
AB  - Many clinical reports suggest that deciduous teeth exhibit a greater
      susceptibility to resorption than permanent ones. To examine the difference
      between deciduous and permanent dentine in their susceptibility to osteoclastic
      resorption, osteoclast-like cells (OCLs) were cultured on deciduous and permanent
      dentine slices. The number, area, depth, and volume of resorption pits were then
      measured, using image-analyzing systems. We measured the level of degraded
      collagen (cross-linked N-telopeptide of type I collagen; NTx) in culture medium
      using an enzyme-linked immunosorbent assay (ELISA). The levels of cathepsin K,
      matrix metallo proteinase (MMP)-9, and MMP-13 mRNAs in the cells attached to
      dentine were also analyzed by real-time reverse transcription polymerase chain
      reaction (RT-PCR). Deciduous dentine slices exhibited a significant (twofold)
      increase in resorbed area compared with the permanent slices. Three-dimensional
      analysis revealed that the volume of pits in deciduous dentine differed
      significantly (fourfold) compared to that in the permanent dentine. The depth of
      pits also followed the same trend. However, there was no significant difference
      in the number of pits or osteoclasts on the dentine slices. The NTx level in
      deciduous media was significantly more than that in permanent media. The mRNA
      levels also followed the same trend. These results suggest that deciduous dentine
      is more susceptible to resorption than permanent dentine and signals from the
      substrate play an important role in physiological resorption.

PMID- 16622741
TI  - Tumor angiogenesis and antiangiogenic therapy: current status and perspective.

PMID- 16622740
TI  - Bisphosphonate pretreatment attenuates hungry bone syndrome postoperatively in
      subjects with primary hyperparathyroidism.
AB  - Primary hyperparathyroidism is characterized by hypercalcemia with loss of bone
      mass. After parathyroidectomy, hypocalcemia may develop in some patients due to
      unregulated bone mineralization. Preoperative administration of bisphosphonates,
      potent inhibitors of osteoclast activity, may prevent postoperative hypocalcemia
      after parathyroidectomy. We retrospectively reviewed medical records to
      investigate the effect of bisphosphonate pretreatment on serum calcium level
      changes after parathyroidectomy. Twenty-three patients with a diagnosis of
      primary hyperparathyroidism underwent parathyroidectomy between April 1997 and
      August 2002. Clinical and laboratory data were collected before and after the
      operation. These patients were divided into two groups; those showing hungry bone
      syndrome (n = 9) and those not (n = 14). None of the 9 patients with hungry bone
      syndrome had received bisphosphonate pretreatment. Of the 14 patients without
      hungry bone syndrome, 6 had received bisphosphonate pretreatment (P < 0.05).
      Furthermore, preoperative calcium concentration was not related to the occurrence
      of hypo-calcemia in those without bisphosphonate pretreatment. In conclusion,
      administration of bisphosphonates in primary hyperparathyroidism can prevent the
      occurrence of hungry bone syndrome after parathyroidectomy.

PMID- 16622742
TI  - Current status and perspective of angiogenesis and antivascular therapeutic
      strategy: non-small cell lung cancer.
AB  - Lung cancer is the leading cause of cancer death worldwide, and most patients die
      of metastatic disease. Angiogenesis, namely, neovascularization from preexisting
      vasculature, is necessary for tumor growth in both primary and distant organs to
      supply oxygen and nutrition. Angiogenesis consists of sprouting and nonsprouting
      (the enlargement, splitting, and fusion of preexisting vessels) processes, and
      both can occur concurrently. The growth of non-small cell lung cancer (NSCLC),
      which accounts for more than 80% of all lung cancers, is usually dependent on
      angiogenesis, which is regulated by complex mechanisms in the presence of various
      angiogenesis-related molecules. Vascular endothelial growth factor (VEGF), also
      known as vascular permeability factor (VPF), is one of the most potent angiogenic
      molecules, while also regulating both angiogenesis and vascular permeability and
      hence promoting tumor progression and the development of malignant pleural
      effusions in NSCLC. Recent clinical trials showed that the anti-VEGF antibody
      bevacizumab, combined with standard first-line chemotherapy, provided a
      statistically and clinically significant survival advantage with tolerable
      toxicity. In addition, the combined use of the anti-VEGF antibody with an
      inhibitor of epidermal growth factor receptor (EGFR) has also shown favorable
      antitumor efficiency. These successes proved the validity of an antivasculature
      strategy for NSCLC. Furthermore, a large number of antivasculature agents have
      been shown to be effective against multiple targets. The efficiency of these
      compounds is currently being investigated in clinical trials for NSCLC.

PMID- 16622743
TI  - Current status and perspective of antiangiogenic therapy for cancer:
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is well known as a typical angiogenic tumor,
      especially in the moderately to poorly differentiated type. Such
      clinicopathological characteristics are not only useful for imaging diagnosis but
      are also applicable to the treatment of HCC. In addition, recent molecular
      studies have revealed that angiogenesis is closely related to
      hepatocarcinogenesis. In this review, the molecular mechanism of HCC angiogenesis
      and the antiangiogenic prevention of HCC are reviewed to introduce the latest
      trends in antiangiogenic treatment of cancers, including HCC.

PMID- 16622746
TI  - Oncologic outcome of parosteal osteosarcoma.
AB  - BACKGROUND: This retrospective review evaluated the clinical features and
      surgical outcomes of parosteal osteosarcoma (POS). METHODS: Nine patients were
      surgically treated and followed up. Their mean age was 30.8 years. Clinical
      information and oncologic outcomes of each case were analyzed. RESULTS: Sites of
      involvement were all in the femur, and all tumors arose from the metaphyseal area
      of the distal femur. Biopsies for definite diagnoses were performed in just two
      of the nine cases. Wide resection was applied for all tumors. Surgical
      evaluations were a 1-cm-wide procedure in six cases and a 2-cm-wide procedure (or
      more) in three cases. All patients were found to be continuously disease free
      during the follow-up period of 115.1 months. CONCLUSION: POS showed
      characteristic findings on radiographic images. Therefore, wide resection without
      biopsy could be performed in 77.8% (7/9) of the cases. This procedure may
      contribute to attaining better limb function, because of preventing contamination
      of healthy surrounding tissue and minimizing the extent of resection. The safety
      margin was evaluated as a 1-cm-wide procedure. For the choice of reconstruction,
      indication of autobone grafting (3/9) or total knee replacement (TKR) (6/9)
      depended on tumor size, location, and shape. With no adjuvant treatments, all
      cases have shown good clinical courses during the entire follow-up period of
      about 10 years.

PMID- 16622745
TI  - Early breast cancer.
AB  - Breast cancer remains a common disease throughout the world. Here we review new
      knowledge about early breast cancer obtained during the past 5 years. The
      prognosis of early breast cancer is generally favorable. Especially, ductal
      carcinoma in situ has been regarded as a non-life-threatening disease. Therefore,
      early diagnosis and early onset of the treatment has been important. Early age at
      menarche, late age at first birth, and late age at menopause are related to
      breast cancer risk. Examination by mammography and ultrasonography is still the
      most effective means of detection for premenopausal and postmenopausal women,
      respectively. Additionally, there have been important advances in MRI, sentinel
      lymph node biopsy, breast-conserving surgery, partial breast irradiation,
      neoadjuvant systemic therapy, and adjuvant systemic therapy. Another approach to
      keeping the disease under control is the elucidation of breast cancer's molecular
      biological features. Assessment of potential molecular targets can lead to early
      diagnosis and molecular targeted treatment.

PMID- 16622744
TI  - Current status and perspective of antiangiogenic therapy for cancer: urinary
      cancer.
AB  - Angiogenesis is considered a prerequisite for solid tumor growth. Antiangiogenic
      therapy reduces tumor size and extends host survival in a number of preclinical
      animal models. However, in humans antiangiogenic therapy is a poor promoter of
      tumor regression and has shown minimal effect on patient survival. In urinary
      cancers, such as renal cell cancer, prostate cancer, and bladder cancer, advanced
      refractory disease is a good candidate for antiangiogenic therapy because of its
      resistance to ordinary chemotherapy, radiotherapy, and hormonal therapy. Unique
      characteristics of molecular mechanisms underlie the induction of angiogenesis in
      urinary cancers. In this review, we summarize these unique mechanisms and review
      the results of clinical trials of antiangiogenic therapy for these cancers,
      discussing prospects and problems relating to antiangiogenic therapy.

PMID- 16622747
TI  - Three-dimensional combination of transrectal and transperineal biopsies for
      efficient detection of stage T1c prostate cancer.
AB  - BACKGROUND: Although an increasing number of men present with stage T1c prostate
      cancer, the optimal biopsy strategy for detecting stage T1c disease still remains
      to be defined. The aim of this study was to explore an efficient first-time
      biopsy scheme for detecting stage T1c and T2 prostate cancer. METHODS: A
      transrectal ultrasound-guided systematic three-dimensional 26-core (3D26) biopsy
      comprising 12 transrectal and 14 transperineal sampling sites was performed in
      321 men with median prostate-specific antigen (PSA) level of 6.0 ng/ml in the
      first-time biopsy setting. By analyzing site-specific cancer detection rates, we
      determined the best combination of transperineal and transrectal sampling sites.
      RESULTS: Prostate cancer was detected in 109 of the 321 men (34%) with a major
      complication rate of 0.6%. 3D26 biopsy significantly improved cancer
      detectability by 60% relative to the conventional transrectal sextant (TR6)
      biopsy. Improvement was significant in 263 men with normal digital rectal
      examination (DRE) (85%, P = 0.0004) but not in 58 men with abnormal DRE (22%, P =
      0.18). The mean Gleason score of the 41 cancers without a positive core within
      the TR6 sites was marginally lower than that of 68 cancers with a positive core
      within the TR6 sites (P = 0.04). Recursive partitioning revealed that a three
      dimensional 14-core (transrectal 8-core plus transperineal 6-core) and a three
      dimensional 8-core (transrectal 4-core plus transperineal 4-core) biopsies could
      detect more than 95% of stage T1c and T2 cancers with a minimum number of cores,
      respectively. CONCLUSION: We propose a three-dimensional 14-core and a three
      dimensional 8-core biopsy as efficient first-time biopsy schemes to detect stage
      T1c and T2 prostate cancer, respectively.

PMID- 16622748
TI  - Does a selective cyclooxygenase-2 inhibitor (tiracoxib) induce clinically
      sufficient suppression of adenomas in patients with familial adenomatous
      polyposis? A randomized double-blind placebo-controlled clinical trial.
AB  - BACKGROUND: There have been few placebo-controlled randomized double-blind
      studies of the clinical effects of selective cyclooxygenase-2 (COX-2) inhibitors
      on the regression of colorectal tumors. This study was designed to examine the
      regressive effect of a selective COX-2 inhibitor, tiracoxib (JTE-522), on
      colorectal polyps in patients with familial adenomatous polyposis (FAP), and its
      safety. METHODS: Sixty-one patients with FAP diagnosed by Japanese criteria were
      assigned randomly to receive placebo or JTE-522, at either 150 mg or 200 mg, once
      daily orally for 26 weeks. Prior to and at the end of the medication period,
      endoscopy was performed. Adenomas located near an india-ink tattoo injected at
      the first colonoscopy were identified and measured. The response variables were
      the percent changes from the baseline in polyp numbers and in specified polyp
      diameters. Any adverse events that appeared in at least four persons were taken
      into consideration and compared between the JTE-522 treatment groups and the
      placebo group. RESULTS: No change in polyp number (median, 0) was observed in any
      of the three groups. There were no differences between the placebo group and the
      two treatment groups in the change in polyp size. JTE-522 was well tolerated.
      CONCLUSION: Our findings, in keeping with other reports on COX-2 inhibitors,
      indicated that the inhibition of a COX-2 with a moderate dose of a selective COX
      2 inhibitor did not induce clinically sufficient regression of adenomas in
      patients with FAP in a limited (6-month) medication period.

PMID- 16622749
TI  - Associations of TNF-A-1031TT and -857TT genotypes with Helicobacter pylori
      seropositivity and gastric atrophy among Japanese Brazilians.
AB  - BACKGROUND: Our previous study in a Japanese population showed elevated
      Helicobacter pylori seropositivity in those with tumor necrosis factor (TNF) A 
      1031TT and -857TT genotypes. This study examined the associations of this
      seropositivity and serum pepsinogen (PG) levels with these genotypes in Japanese
      Brazilians. METHODS: The subjects were 963 individuals (399 males and 564
      females), aged 33 to 69 years, from four regions (Sao Paulo, Curitiba, Mogi das
      Cruzes, and Mirandopolis) in Brazil. Gastric atrophy was evaluated with serum
      pepsinogens (PGI < 70 ng/dl and PGI/II < 3), and TNF T-1031C and C-857T were
      genotyped by polymerase chain reaction with confronting two-pair primers (PCR
      CTPP). RESULTS: The frequency of TNF-A T-1031C was 68.4% TT, 28.4% TC, and 3.3%
      CC, and that of C-857T was 64.5% CC, 31.7% CT, and 3.8% TT, whose distributions
      were in Hardy-Weinberg equilibrium. No significant associations of the genotypes
      with H. pylori seropositivity or gastric atrophy were found. However, male
      participants with TNF-A -1031CC and -857CC showed the lowest seropositivity
      (43.8% out of 16), and males with TNF-A -1031TT and -857TT showed the highest
      (61.5% out of 13). CONCLUSION: This study demonstrated that the associations
      between H. pylori seropositivity and TNF-A genotypes were not marked for Japanese
      Brazilians. The genotypes were not associated with gastric atrophy among the
      seropositive individuals.

PMID- 16622750
TI  - Successful delivery after vaginal radical trachelectomy for invasive uterine
      cervical cancer.
AB  - A 32-year-old Japanese woman was diagnosed as having stage Ib1 adenocarcinoma by
      diagnostic laser conization at a local hospital. She was admitted to our hospital
      for fertility-sparing treatment. A radical trachelectomy (RT) was performed using
      the laparoscopic vaginal procedure. The procedure was started with a laparoscopic
      pelvic lymphadenectomy. As the lymph nodes were tumor free, RT was carried out
      transvaginally. The excised uterine cervix and lymph nodes were pathologically
      negative for cancer. Eight months after the operation, the patient became
      pregnant without any artificial reproduction techniques. At 17 weeks of
      gestation, she was admitted to our hospital again for a threatened abortion.
      Continuous tocolytic treatment with ritodrine and daily administration of a
      granulocyte elastase inhibitor vaginal suppository were given. At 32 weeks of
      gestation, she underwent emergency cesarean section because of sudden premature
      rupture of the membranes. A girl weighing 1991 g was delivered, with Apgar scores
      of 7 and 8 at 1 and 5 min, respectively. Both the mother and the baby were
      discharged without trouble. This is the first successful case in Japan of
      delivery after vaginal RT for invasive uterine cervical cancer.

PMID- 16622751
TI  - Tamoxifen for recurrent desmoid tumor of the chest wall.
AB  - We report a case of a young woman with recurrent desmoid tumor. Computed
      tomography (CT) scans of the chest showed a large mass in the left chest wall.
      The tumor was unresectable because of the involvement of adjacent structures.
      Tamoxifen therapy led to marked tumor regression within 3 months. She had
      preserved her fertility, and thereafter she conceived a baby. In young women with
      recurrent desmoid tumor, tamoxifen should be considered as the first choice of
      treatment.

PMID- 16622752
TI  - Nonpuerperal inversion of the uterus associated with endometrial cancer: a case
      report.
AB  - Few nonpuerperal uterine inversions have been reported, with only 101 cases
      during the period from 1940 to date. Moreover, uterine inversion resulting from
      endometrial cancer is an extremely rare condition, with only 7 reported cases. In
      this article, we present a case of a patient with uterine inversion caused by
      endometrial cancer that could be diagnosed and treated with surgery. We also
      discuss the mechanism of onset and present a review of the literature.

PMID- 16622753
TI  - Intensive multimodality therapy including paclitaxel and reduced-intensity
      allogeneic hematopoietic stem cell transplantation in the treatment of adrenal
      cancer with multiple metastases.
AB  - Adrenocortical carcinoma is a rare malignancy in adolescents and young adults.
      The prognosis of unresectable/metastatic adrenocortical carcinoma remains very
      poor because the rarity of the tumor has made it difficult to establish treatment
      guidelines, and diagnosis and the resultant treatment can be greatly delayed. We
      treated a 24-year-old woman who was diagnosed with adrenocortical carcinoma of
      the right adrenal gland which extended to the inferior vena cava. Although she
      underwent surgical resection of the extensive tumor as the primary treatment, the
      disease recurred in the lung and liver as multiple metastases shortly after
      surgery. She received intensive multimodality therapy, including chemotherapy
      with paclitaxel, ifosfamide, and cisplatin (TIP regimen), embolization of the
      feeding arteries, and proton irradiation for the liver mass. Finally, she
      underwent reduced-intensity allogeneic hematopoietic stem cell transplantation
      from an HLA 1-locus-mismatched sibling donor. A prolonged survival of 39 months
      after the onset of the disease was achieved. Although this experience is limited,
      we suggest that TIP chemotherapy was effective for adrenocortical carcinoma, and
      a graft-versus-tumor effect after reduced-intensity stem cell transplantation may
      have contributed to the prolonged survival.

PMID- 16622754
TI  - A case of gastric lymphoma with marked interfractional gastric movement during
      radiation therapy.
AB  - Radiation therapy (RT) with or without chemotherapy has been a widely accepted
      treatment for patients with localized gastric lymphoma. We encountered a patient
      with gastric diffuse large B-cell lymphoma, whose stomach volume, and the
      position and location of the clips that had been endoscopically placed to define
      the gastric lesions clearly differed considerably at three simulation times. The
      positions of the clips moved between 5 and 35 mm (mean 24 mm) laterally on
      simulation films. The mean movement of these clips along the cephalocaudal
      directions was 8 mm (range 0-15 mm). There have been no published articles which
      systemically evaluated interfractional gastric motion between each treatment
      session. Therefore this is an important observation in the management of patients
      with gastric lymphoma with RT.

PMID- 16622757
TI  - Letter to the editor.

PMID- 16622758
TI  - Socially strategic ecological restoration: a game-theoretic analysis [corrected].
AB  - Major transitions in a multiple-use or mosaic landscape often lead to frictions
      among new and existing users. In this article, we consider the problem of
      ecological restoration within a mosaic landscape in which restoration activities
      elicit feedbacks from individuals and groups that are harmed by restoration
      outcomes. Using game theory, we identify three potential outcomes ranked by the
      extent of restoration of ecosystem services and processes: nonstrategic,
      noncooperative strategic equilibrium, and cooperative bargaining solution. We
      identify conditions under which additional restoration can decrease the overall
      flow of ecosystem services and processes. A "strategic restorationist" will cease
      new restoration activities when the net effect of defensive response moves by
      farmers offsets gains. Imperfect information regarding expected payoffs to
      farmers can lead to inefficient overshooting or undershooting the optimal scale,
      geographical positioning, and form of restoration. Gains to all parties from
      cooperation might exist. As a case study and to aid model design, we consider
      restoration activities on California's upper Sacramento River.

PMID- 16622759
TI  - Use of artificial roost structures by bats at the Indianapolis International
      Airport.
AB  - From 1992-1996, 3204 artificial roosts of 9 types were placed in woodlots near
      Indianapolis International Airport in an effort to provide habitat for the
      federally-endangered Indiana myotis (Myotis sodalis) and to determine the
      feasibility of using these structures to manage bats in a rapidly developing
      suburban area. We surveyed these structures at least annually during 1992-1999
      and found only northern myotis (Myotis septentrionalis) regularly using the
      structures. Four other species were occasionally found using structures including
      big brown bats (Eptesicus fuscus, n=14 individuals), little brown myotis (Myotis
      lucifugus, n=2), Indiana myotis (Myotis sodalis, n=2), and one silver-haired bat
      (Lasionycteris noctivagans). Single, triple, and Missouri-style batboxes were
      almost always used, rather than the six other types of experimental roosts that
      had been in place. However, after 10 years in place, it appears that Indiana bats
      are acclimated to boxes, as 6 of them were being used rather regularly by Indiana
      myotis. Bat boxes can provide roosting habitat for some species under conditions
      where few suitable roosts exist, but assuring an abundance of natural habitats is
      usually more desirable for conservation of tree-roosting bats.

PMID- 16622773
TI  - Oxidant-antioxidant balance in patients with COPD.
AB  - The goal of this study was to evaluate the role of oxidant-antioxidant balance in
      the pathogenesis of COPD. We included 30 healthy nonsmokers [24 male, 6 female;
      mean age (yr) +/- SD: 62.4 +/- 9.3], 30 healthy smokers [27 male, 3 female; mean
      age (yr) +/- SD: 58.7 +/- 6.0], 71 patients with stable COPD [68 male, 3 female;
      mean age (yr) +/- SD: 63.5 +/- 7.9], and 31 patients with COPD exacerbation [30
      male, 1 female; mean age (yr) +/- SD: 64.2 +/- 7.3]. In all study groups the
      peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a
      parameter of lipid peroxidation caused by the oxidants, and erythrocyte
      superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was
      higher in healthy smokers and in patients with COPD than in healthy nonsmokers (p
      < 0.05), and erythrocyte SOD enzyme activity in patients with COPD exacerbation
      (1048.2 +/- 226.5 Ug/Hb) was significantly higher than in healthy nonsmokers
      (947.9 +/- 198.0 Ug/Hb) (p < 0.05). Although mean erythrocyte SOD enzyme activity
      in healthy smokers and patients with stable COPD was higher than in healthy
      nonsmokers, the difference was not statistically significant. We found that
      healthy smokers and stable and exacerbated COPD patients had an impairment in
      oxidant-antioxidant balance. We suggested that new therapeutic interventions,
      which may repair the impaired oxidant-antioxidant balance in COPD, are needed to
      prevent the development of COPD.

PMID- 16622774
TI  - Technetium-99m hexamethylpropylene amine oxime lung scintigraphy findings in low
      dose amiodarone therapy.
AB  - Amiodarone (AD)-induced pulmonary toxicity is one of the major complications of
      long-term AD therapy. Technetium-99m-labeled D: ,L: -hexamethylpropylene amine
      oxime (Tc-99m HMPAO) scintigraphy has been used to assess lung injury. We
      designed this study to clarify lung uptake changes of Tc-99m HMPAO using low
      doses of AD (5 mg/kg/day) during long-term therapy in a rabbit model. Group 1
      consisted of 7 rabbits fed with AD by gavage for 6 months. To investigate the
      effect of ketamine on Tc-99m HMPAO uptake, 5 rabbits were included in Group 2 as
      a control group. Tc-99m HMPAO scintigraphy was performed in both Group 1 and
      Group 2 at baseline and after 2, 4, 6, 8, and 12 weeks of AD intake. After 16,
      20, and 24 weeks of drug intake, Tc-99m HMPAO scintigraphy was repeated only in
      group 1. One-min anterior images were acquired 30 min after the injection of 37
      MBq of Tc-99m HMPAO. For semiquantitative evaluation, the mean count values were
      obtained and lung/background and liver/background ratios were calculated.
      Histopathologic evaluation was performed. No increase in lung and liver uptake of
      Tc-99m HMPAO was found 2, 4, 6, 8, and 12 weeks after drug intake. There was no
      significant increase in L/B and H/B ratios of Tc-99m HMPAO in Group 1 compared
      with Group 2. Both scintigraphic studies and histopathologic examinations showed
      nonspecific changes. Longitudinal studies investigating Tc-99m HMPAO lung uptake
      may be planned in patients carrying risk factors for AD-induced lung toxicity.

PMID- 16622775
TI  - Effects of early intervention with inhaled sodium cromoglycate in childhood
      asthma.
AB  - International and Japanese guidelines classify childhood asthma as mild,
      moderate, or severe, and recommend treatment with "as needed" bronchodilators,
      inhaled sodium cromoglycate, and inhaled corticosteroids, respectively.
      Alternatively, some investigators proposed inhaled corticosteroids as first-line
      therapy to prevent airway inflammatory obstruction. This article describes a
      clinical study assessing the effect of early intervention with inhaled sodium
      cromoglycate in childhood asthma. This was a retrospective study of 189 asthmatic
      children treated with inhaled sodium cromoglycate for five years and whose age of
      onset of asthma was six year of age or younger. An end-of-study questionnaire
      completed the examination. Children administered oral or inhaled corticosteroids
      simultaneously with sodium cromoglycate, were excluded. Asthma scores as defined
      by the Japanese Pediatric Allergic Committee, were reduced continuously during
      the five years after the start of sodium cromoglycate treatment. The frequency of
      emergency department visits and hospitalizations also decreased. Significant
      between-period intervention differences showed improvement of clinical outcomes
      for children with severe asthma during the five years of sodium cromoglycate
      inhalation. The early intervention regime of starting sodium cromoglycate
      inhalation within two years of the onset of asthma shows a large improvement in
      the long-term prognosis of childhood asthma, especially for children with severe
      asthma. It is possible that starting inhaled sodium cromoglycate earlier than the
      present recommendation of corticosteroids could further improve clinical
      outcomes, but a prospective study should be performed to verify our results.

PMID- 16622776
TI  - Relationship among pulmonary function, bronchial hyperresponsiveness, and atopy
      in children with clinically stable asthma.
AB  - Pulmonary function testing plays a key role in the diagnosis and management of
      asthma in children. However, the literature does not clearly show whether
      children with clinically stable asthma have significantly reduced lung function
      when compared with normal children. We compared the lung function of 242
      clinically stable asthmatic children who were initially diagnosed with mild
      intermittent or mild persistent asthma with the lung function of 100 nonasthmatic
      controls. The lung function was assessed using FEV1, FEV1/FVC, FEF25-75 and PEF.
      In addition, we measured bronchial hyperresponsiveness (BHR) using the
      provocation concentration of methacholine needed to produce a 20% fall in FEV1.
      All measures of pulmonary function were significantly decreased in the children
      with asthma. Pulmonary function was not influenced by atopy, serum IgE, or total
      eosinophil count (TEC). However, the likelihood ratio for trends revealed a
      significant association between our pulmonary parameters and the degree of BHR.
      Children with mild-to-severe BHR had greatly decreased lung function compared
      with those with normal BHR, the control group. In addition, a direct correlation
      was found between PC20 and our pulmonary parameters in asthmatic children.
      However, only atopic children with asthma had a significant correlation between
      PC20 and TEC. We found children with clinically stable asthma to have pulmonary
      obstruction, which associated strongly with their degree of BHR.

PMID- 16622777
TI  - Activation and degradation of protein C by primary rabbit pleural mesothelial
      cells.
AB  - The protein C (PC) anticoagulant pathway is the major mechanism that controls
      thrombin generation in vivo and may thereby influence pathophysiologic fibrin
      turnover associated with intrapleural inflammation. We hypothesized that pleural
      mesothelial cells could regulate local expression of PC in evolving pleurodesis
      where inflammation and thrombosis play an important role. To test this
      hypothesis, we determined the ability of rabbit pleural mesothelial cells (RPMC)
      to support the activation of PC as well as its binding, internalization, and
      degradation. Lung fibroblasts were also assessed to test the specificity of the
      responses. We found that both cell types could support thrombin-dependent
      activation of PC in vitro. Both cell types were capable of binding,
      internalizing, and degrading 125I-PC. Degradation of 125I-PC by these cells was
      prevented by the lysosomal inhibitor chloroquine but not the proteasomal
      inhibitor lactacystin, supporting involvement of a lysosomal mechanism of PC
      degradation. During evolving tetracycline (TCN)-induced pleural injury in
      rabbits, PC levels in pleural fluids were sustained, exhibited a trend toward
      progressive decline, and were temporally correlated with pleural adhesion
      formation in vivo. These observations indicate that sustained expression of PC
      during evolving pleurodesis induced by TCN is subject to regulation by resident
      pleural cells: both RPMC and lung fibroblasts. Both cell types support local
      generation of APC. Internalization and degradation of PC by RPMC and fibroblasts
      may regulate its intrapleural expression and influence remodeling of
      extravascular fibrin in the setting of evolving pleurodesis induced by TCN.

PMID- 16622778
TI  - Effect of PKC isozyme inhibition on forskolin-induced activation of BKCa channels
      in rat pulmonary arterial smooth muscle.
AB  - Signaling mechanisms that elevate cyclic AMP (cAMP) activate large-conductance,
      calcium- and voltage-activated potassium (BKCa) channels in vascular smooth
      muscle and cause vasodilatation. In pulmonary vascular smooth muscle (PVSM), BKCa
      channel modulation is important in the regulation of pulmonary arterial pressure,
      and inhibition (closing) of the BKCa channel causes pulmonary vasoconstriction.
      Protein kinase C (PKC) modulates BKCa channels in systemic vascular smooth
      muscle, but little is known about the effect of PKC on BKCa channel activity in
      PVSM. A novel finding from our laboratory showed that PKC activates BKCa channels
      in rat pulmonary arterial smooth muscle and, having observed that cAMP-elevating
      agents also open BKCa channels, we hypothesized that PKC may open BKCa channels
      via a cAMP-dependent mechanism. Forskolin (10 microM), an activator of adenylyl
      cyclase, which increases cAMP concentration, opened BKCa channels in single
      pulmonary arterial smooth muscle cells (PASMC) of the Sprague-Dawley rat. The
      effect of forskolin was completely blocked by the PKC inhibitor Go 6983, which
      selectively blocks the alpha, beta, delta, gamma, and zeta PKC isozymes, and, by
      rottlerin, which selectively inhibits PKCdelta, and partially blocked by Go 6976,
      which selectively inhibits PKCalpha PKCbeta, and PKCmu. These results indicate
      that specific PKC isozymes mediate forskolin-induced activation of BKCa channels
      in PASMC, which suggests that a signaling pathway involving PKC activation and
      cAMP exists in pulmonary arterial smooth muscle to open BKCa channels.

PMID- 16622779
TI  - TNF-alpha promoter polymorphism in relation to TNF-alpha production and clinical
      status in cystic fibrosis.
AB  - The severity of lung disease in cystic fibrosis may be related to the genetic
      propensity of the host to produce tumor necrosis fector alpha (TNF-alpha). A
      polymorphism in the promoter region of the TNF-alpha gene at nucleotide 308
      relative to the transcription start site may be important in determing the host's
      TNF-alpha response. The aim of this study was to assess the correlation between a
      TNF-308 promoter polymorphism, ex vivo TNF-alpha production (before and after
      lipopolysaccharide (LPS) stimulation), and clinical status [FEV1, weight (z
      score), BMI, Shwachman score, incidence of diabetes mellitus, and Pseudomonas
      aeruginosa infection). Genotyping for the biallelic TNF-308 polymorphism was
      performed by using a real-time PCR cycler. Patients (homozygous for Delta F 508)
      were grouped according to genotype (TNF2 carriers, n = 16, median age = 15 yr,
      female/male = 5/11; TNF1 homozygotes, n = 37, median age = 21 yr, female/male =
      18/19). TNF-alpha was measured using a chemiluminescent immunometric assay. There
      was a trend toward higher TNF-alpha values [median TNF2 carriers vs. TNF1
      homozygotes: x = 56 vs. 43.5 pg/ml, n.s. (Mann-Whitney U-test] in those carrying
      the polymorphism and better lung function results [FEV(1) (%) 81 vs. 65, n.s.].
      These differences equalized [TNF2 carriers vs. TNF1 56 vs. 51 pg/ml, n.s.; FEV1
      (%) 84 vs. 79, n.s.] after age adjustment (+/- 2 yr, n = 15, median age TNF2 vs.
      TNF1-17/18 yr). There were no significant differences for TNF values after LPS
      stimulation and the incidence of diabetes mellitus. The TNF-308 promoter
      polymorphism does not seem to influence TNF-alpha release in whole blood cells
      and clinical status.

PMID- 16622780
TI  - Pleurodesis induced by talc or silver nitrate: evaluation of collagen and elastic
      fibers in pleural remodeling.
AB  - This study evaluated the extracellular matrix (collagen and elastic fibers) in
      pleurodesis induced by intrapleural talc (TL) or silver nitrate (SN). Study
      subjects were 420 rabbits divided into two groups and sacrificed from 15 min to
      12 months after the injection of the sclerosing agents at intervals previously
      defined. Pleural adhesions and fibrosis were graded (0-4), and the collagen and
      elastin were quantified. The maximum score of the pleural adhesions was observed
      two months after TL (2.80 +/- 0.99) and 15 days after SN (3.75 +/- 0.25). More
      intense pleural adhesions were observed in the SN group from day 5 (p < 0.05).
      Pleural thickness and pleural fibrosis were, in general, significantly higher
      after SN (p < 0.05). Increased deposition of collagen and elastin was observed in
      both groups but was more evident in the SN group. In the TL group, a linear
      correlation was observed between pleural adhesions and fibrosis (r = 0.775),
      between pleural adhesions and collagen (r = 0.779), and between fibrosis and
      collagen (r = 0.709). In the SN group, these correlations were acceptable (r =
      0.605, 0.665, and 0.663). The elastin presented a correlation of 0.707 (p <
      0.001) in the TL group and of 0.564 (p < 0.001) in the SN group. In conclusion,
      intrapleural 0.5% silver nitrate and talc (400 mg/kg) are effective in the
      induction of pleurodesis. However, the intensity of adhesions and the richness of
      collagen after SN, in combination with the early onset of tissue remodeling,
      demonstrate the local superiority of this agent. Considering the easy
      availability and instillation, the low cost, and the absence of important side
      effects, silver nitrate might be considered as a sclerosing agent to induce
      pleurodesis in humans.

PMID- 16622781
TI  - The effects of age on exhaled breath nitric oxide levels.
AB  - A variety of factors influence exhaled breath nitric oxide (ENO) but few studies
      have examined ENO at the extremes of adult age. This investigation explores
      whether there is a difference in ENO between groups of older and younger
      individuals. A total of 48 normal subjects consisting of 23 younger (median age -
      24 years) and 25 older (median age - 72 years) participants were studied.
      Carefully defined clinical and spirometric parameters, smoking history, and
      drug/medication documentation were determined to insure normalcy. Measurements of
      ENO were made using ATS/ERS recommended methodologies. The older group
      consistently showed higher ENO concentrations than-the younger subjects; median
      ENO values were 36.9 and 18.7 ppb, respectively (p < 0.001). The statistical
      significance held true when adjusting for multiple testing with the Holm method
      and accounting for outliers and medication usage. ENO levels are significantly
      higher in a normal older population. Comparing ENO between individuals at the
      extremes of age may depict differences more decidedly. Whether elevated ENO
      reflects underlying airway inflammation in older persons remains unanswered. It
      is possible that the difference in NO concentrations between older and younger
      groups represents only a marker of past oxidant exposures and holds no clinical
      significance. Additional investigations are necessary to elucidate the mechanisms
      and significances of elevated NO levels in the aged.

PMID- 16622782
TI  - Identification of C4 responsive genes in the facultative C4 plant Hydrilla
      verticillata.
AB  - The aquatic monocot Hydrilla verticillata (L.f.) Royle is a well-documented
      facultative C4 NADP-malic enzyme species in which the C4 and Calvin cycles
      operate in the same cell with the specific carboxylases confined to the cytosol
      and chloroplast, respectively. Several key components had already been
      characterized at the molecular level, thus the purpose of this study was to begin
      to identify other, less obvious, elements that may be necessary for a functional
      single-cell C4 system. Using differential display, mRNA populations from C3 and
      C4 H. verticillata leaves were screened and expression profiles compared. From
      this study, 65 clones were isolated and subjected to a customized macroarray
      analysis; 25 clones were found to be upregulated in C4 leaves. Northern and semi
      quantitative RT-PCR analyses were used for confirmation. From these screenings,
      13 C4 upregulated genes were identified. Among these one encoded a previously
      recognized C4 phosphoenolpyruvate carboxylase, and two encoded distinct pyruvate
      orthophosphate dikinase isoforms, new findings for H. verticillata. Genes that
      encode a transporter, an aminotransferase and two chaperonins were also
      upregulated. Twelve false positives, mostly housekeeping genes, were determined
      from the Northern/semi-quantitative RT-PCR analyses. Sequence data obtained in
      this study are listed in the dbEST database (DV216698 to DV216767). As a single
      cell C4 system that lacks Kranz anatomy, a better understanding of how H.
      verticillata operates may facilitate the design of a transgenic C4 system in a C3
      crop species.

PMID- 16622783
TI  - Investigation of Rhodobacter capsulatus PufX interactions in the core complex of
      the photosynthetic apparatus.
AB  - The photosynthetic apparatus of purple bacteria in the genus Rhodobacter includes
      a core complex consisting of the reaction centre (RC), light-harvesting complex 1
      (LH1), and the PufX protein. PufX modulates LH1 structure and facilitates
      photosynthetic quinone/quinol exchange. We deleted RC/LH1 genes in pufX+ and
      pufX++ (merodiploid) strains of Rhodobacter capsulatus, which reduced PufX levels
      regardless of pufX gene copy number and location. Photosynthetic growth of RC
      only strains and independent assembly kinetics of the RC and LH1 were unaffected
      by pufX merodiploidy, but the absorption spectra of strains expressing the RC
      plus either LH1 alpha or beta indicated that PufX may influence
      bacteriochlorophyll binding environments. Significant self-association of the
      PufX transmembrane segment was detected in a hybrid protein expression system,
      consistent with a role of PufX in core complex dimerization, as proposed for
      other Rhodobacter species. Our results indicate that in R. capsulatus PufX has
      the potential to be a central, homodimeric core complex component, and its
      cellular level is increased by interactions with the RC and LH1.

PMID- 16622784
TI  - High throughput two-dimensional blue-native electrophoresis: a tool for
      functional proteomics of cytoplasmatic protein complexes from Chlorobium tepidum.
AB  - Chl. tepidum is a Gram-negative green-sulfur bacterium, which is strict by
      anaerobic and grows by utilizing sulfide or thiosulfate as an electron source.
      Blue native-polyacrylamide gel electrophoresis (BN-PAGE) is widely used for the
      analysis of oligomeric state and molecular mass non-dissociated protein
      complexes. In this study, a number of proteomic techniques were used to
      investigate the oligomeric state enzymes. In particular, the Chl. tepidum-soluble
      proteome was monitored under native condition by using BN-PAGE. The BN-PAGE
      protein complexes map was analyzed by MALDI-TOF MS after trypsin treatment and
      from 42 BN proteins bands, 62 different proteins were identified. Additionally,
      functional information regarding protein-protein interactions was assembled, by
      coupling 2-D BN-PAGE with MALDI-TOF MS. One-hundred and seventy gel bands were
      spotted, out of which 187 different proteins were identified. The identified
      proteins belong to various functional categories like energy metabolism, protein
      synthesis, amino acid biosynthesis, central intermediate metabolism, and
      biosynthesis of cofactors indicating the potential of the method for elucidation
      of functional proteomes.

PMID- 16622785
TI  - The role of antioxidant enzymes in photoprotection.
AB  - The enzymatic component of the antioxidant system is discussed as one of the
      defensive mechanisms providing protection against excessive light absorption in
      plants. We present an analysis of attempts to improve stress tolerance by means
      of the creation of transgenic plants with elevated antioxidant enzyme activities
      and conclude that the effect of such transgenic manipulation strongly depends on
      the manner in which the stress is imposed. The following factors may diminish the
      differences in photosynthetic performance between transgenic plants and wild type
      under field conditions: effective functioning of the thermal dissipation
      mechanisms providing a primary line of defense against excessive light, long-term
      adjustments of the antioxidant system and other photoprotective mechanisms, the
      relatively low level of control over electron transport exerted by the Water
      Water cycle, especially under warm conditions, and a decrease in the content of
      the transgenic product during leaf aging.

PMID- 16622786
TI  - Quantitative comparison of the inhibitory effects of GW5638 and tamoxifen on
      angiogenesis in the cornea pocket assay.
AB  - GW5638 is a novel tissue-selective estrogen receptor (ER) modulator.
      Structurally, it is a derivative of tamoxifen that is known for its inhibitory
      effects on angiogenesis in an ER-independent manner. Therefore, it is possible
      that GW5638 has the same effects as tamoxifen on angiogenesis. To test this
      hypothesis, we used the rat cornea pocket assay and developed a new method that
      could precisely determine the total projected area of microvessels induced by
      basic fibroblast growth factor (bFGF) in the cornea. Animals in the study were
      treated with corn oil (control group), tamoxifen, or GW5638. After treatment, we
      observed that both GW5638 and tamoxifen could inhibit angiogenesis in the cornea
      (P<0.05) and that the inhibitory effects were not mediated by blocking functions
      of estrogen. Meanwhile, GW5638 had minimal effects on the body weight of animals
      whereas tamoxifen significantly reduced the body weight. Based on these
      observations, we concluded that GW5638 was as effective as tamoxifen in
      antiangiogenic treatment but less toxic than tamoxifen.

PMID- 16622787
TI  - Acidophilic microbial communities catalyzing sludge bioleaching monitored by
      fluorescent in situ hybridization.
AB  - Biological autotrophic sulfur oxidation processes have been proposed to remove
      heavy metals from wastewater treatment sludge by bioleaching. We made a
      characterization of the microbial population in batch and continuous sludge
      bioleaching reactors using fluorescent in situ hybridization of fluorescently
      labeled oligonucleotidic probes targeting rRNA in a 'top to bottom approach'.
      Batch incubations of sludge with 0.2% (w/v) elemental sulfur resulted in a pH
      value of 5. Alpha-Proteobacteria hybridizing with probe ALF1b were dominant in
      this incubation. Members of the Acidophilium-group (hybridizing with probe
      Acdp821) of Nitrospira/Leptospirillum phylum (Ntspa712 probe) and from the
      archaeal domain (ARCH915) were also detected. When sludge was incubated with 1%
      elemental sulfur in batch or continuous reactor experiments, final pH values were
      always below 2. Active microbial communities consisted almost exclusively of
      gamma-Proteobacteria (hybridizing with probe GAM42a). However, further
      hybridization experiments with probe Thio820 targeting Acidithiobacillus
      ferroxidans and Acidithiobacillus thioxidans gave negative results. A new probe,
      named THIO181, encompassing all known members of the genus was designed.
      Hybridization perfomed with THIO181 and GAM42a showed a perfect co-localization
      of the hybridization signals. Further hybridization experiments with probe
      THIO181 and THC642, specific for the species Acidithiobacillus caldus, confirmed
      that this bacteria was largely responsible for the sulfur oxidation reaction in
      our acidophilic sludge bioleaching reactors.

PMID- 16622788
TI  - Enological functions of parietal yeast mannoproteins.
AB  - Parietal yeast mannoproteins play a very important role in the overall
      vinification process. Their production and release, both during winemaking and
      aging on lees, depends on the specific yeast strain and the nutritional
      conditions. The following enological functions of parietal yeast mannoproteins
      have been described: (a) adsorption of ochratoxin A; (b) combination with
      phenolic compounds; (c) increased growth of malolactic bacteria; (d) inhibition
      of tartrate salt crystallization; (e) interaction with flor wines; (f) prevention
      of haze; (g) reinforcement of aromatic components; (h) wine enrichment during
      aging on fine lees; (i) yeast flocculation and autolysis in sparkling wines.
      Further discoveries related to their enological functions are foreseeable. Yeast
      derived mannoproteins may well induce chemical, sensorial and health benefits,
      thus greatly improving wine quality.

PMID- 16622789
TI  - Genome-wide expression profile of the mnn2 Delta mutant of Saccharomyces
      cerevisiae.
AB  - The MNN2 gene of S. cerevisiae encodes an alpha (1,2) mannosyl transferase
      required for branching the outer chain of N-linked oligosaccharides (Rayner J.C.
      and Munro S. 1998. J. Biol. Chem. 273: 26836-26843) and it also seems to have
      some effect on the transfer of mannosyl phosphate groups to the inner core
      (Olivero I. et al. 2000. FEBS Lett. 475: 111-116). In order to reveal possible
      interactions of MNN2 expression with other cellular pathways, we analyzed the
      transcriptome of the deletion mutant S. cerevisiae mnn2 Delta using cDNA
      microarrays. We found 151 genes that showed an altered expression level of > or
      =2-fold, 58 of them up-regulated and 93 down-regulated. Quite a high proportion
      of these genes (29%) encode unclassified proteins. In contrast to other defects
      affecting the integrity of the cell wall, deletion of MNN2 does not stimulate the
      expression of any of the genes included in the previously defined 'cell wall
      compensatory cluster' (Lagorce et al. 2003. J. Biol. Chem. 278: 20345-20357). We
      also found that 15% of the selected genes are related to central metabolic
      pathways. In addition, the mnn2 Delta strain seems to have a certain level of
      stimulation of DNA processing reactions while some genes involved in
      intracellular transport pathways are under-regulated.

PMID- 16622790
TI  - Screening for microbial markers in Miocene sediment exposed during open-cast
      brown coal mining.
AB  - Viable microorganisms were found in Miocene lacustrine clays of the cypris
      formation excavated from 200-m below the surface as spoil during open-cast brown
      coal mining (Sokolov Brown Coal Basin, North-Western Bohemia, Czech Republic).
      Both saprotrophic microfungi of the genera Penicillium, Verticillium,
      Cladosporium and Aspergillus as well as heterotrophic bacteria were isolated from
      an intact sediment cores. Heterotrophic bacteria were classified by the MIS
      Sherlock System as representatives of genera Nocardiopsis, Arthrobacter,
      Micrococcus, Kocuria, Rothia, Clavibacter, Bacillus, Paenibacillus,
      Brevibacillus, Microbacterium, Acinetobacter and Pseudomonas. A bacterium found
      among the strains had an atypical fatty acids profile enriched by branched fatty
      acids and polyunsaturated fatty acid (18:3 omega 6) and gave no MIS Sherlock
      match. Phospholipid fatty acids analysis indicates a relatively high (535 pmol g(
      1)) but inhomogeneously distributed viable microbial biomass. Fatty acids
      analyses of non-fractioned lipids (representing viable, storage and dead biomass;
      8390 pmol g(-1)) detected rich and homogenous profiles with fungal, bacterial and
      actinomycetal markers but no protozoan and algal fatty acids markers.

PMID- 16622791
TI  - Halomonas maura is a physiologically versatile bacterium of both ecological and
      biotechnological interest.
AB  - Halomonas maura is a bacterium of great metabolic versatility. We summarise in
      this work some of the properties that make it a very interesting microorganism
      both from an ecological and biotechnological point of view. It plays an active
      role in the nitrogen cycle, is capable of anaerobic respiration in the presence
      of nitrate and has recently been identified as a diazotrophic bacterium. Of equal
      interest is mauran, the exopolysaccharide produced by H. maura, which contributes
      to the formation of biofilms and thus affords the bacterium advantages in the
      colonisation of its saline niches. Mauran is highly viscous, shows thixotropic
      and pseudoplastic behaviour, has the capacity to capture heavy metals and exerts
      a certain immunomodulator effect in medicine. All these attributes have prompted
      us to make further investigations into its molecular characteristics. To date we
      have described 15 open reading frames (ORF's) related to exopolysaccharide
      production, nitrogen fixation and nitrate reductase activity among others.

PMID- 16622792
TI  - Biodiversity of Streptomyces of high-mountainous ecosystems of Kyrgyzstan and its
      biotechnological potential.
AB  - The prevalence of actinomyces of Streptomyces class in various types of soils of
      Kyrghyzstan and the variety of its species have been investigated. It is shown
      that predominant members of Streptomyces complex are in the Cinereus section of
      Chromogenus series which are basically adapted to chestnut and black soil while
      species of the section Roseus of the Fuscus series are adapted in gray, brown,
      and chestnut soils. Their antibiotic and growth-stimulating effect and a great
      opportunity of use in biotechnological process have been determined.

PMID- 16622795
TI  - New leads for selective GSK-3 inhibition: pharmacophore mapping and virtual
      screening studies.
AB  - Glycogen Synthase Kinase-3 is a regulatory serine/threonine kinase, which is
      being targeted for the treatment of a number of human diseases including type-2
      diabetes mellitus, neurodegenerative diseases, cancer and chronic inflammation.
      Selective GSK-3 inhibition is an important requirement owing to the possibility
      of side effects arising from other kinases. A pharmacophore mapping strategy is
      employed in this work to identify new leads for selective GSK-3 inhibition.
      Ligands known to show selective GSK-3 inhibition were employed in generating a
      pharmacophore map using distance comparison method (DISCO). The derived
      pharmacophore map was validated using (i) important interactions involved in
      selective GSK-3 inhibitions, and (ii) an in-house database containing different
      classes of GSK-3 selective, non-selective and inactive molecules. New Lead
      identification was carried out by performing virtual screening using validated
      pharmacophoric query and three chemical databases namely NCI, Maybridge and
      Leadquest. Further data reduction was carried out by employing virtual filters
      based on (i) Lipinski's rule of 5 (ii) van der Waals bumps and (iii) restricting
      the number of rotatable bonds to seven. Final screening was carried out using
      FlexX based molecular docking study.

PMID- 16622796
TI  - Force-field parametrization of retro-inverso modified residues: development of
      torsional and electrostatic parameters.
AB  - Torsional and the electrostatic parameters for molecular mechanics studies of
      retro-inverso modified peptides have been developed using quantum mechanical
      calculations. The resulting parameters have been compared with those calculated
      for conventional peptides. Rotational profiles, which were obtained spanning the
      corresponding dihedral angle, were corrected by removing the energy contributions
      associated to changes in interactions different from torsion under study. For
      this purpose, the torsional energy associated to each point of the profiles was
      estimated as the corresponding quantum mechanical energy minus the bonding and
      nonbonding energy contributions produced by the perturbations that the variation
      of the spanned dihedral angle causes in the bond distances, bond angles and the
      other dihedral angles. These energies were calculated using force-field
      expressions. The corrected profiles were fitted to a three-term Fourier expansion
      to derive the torsional parameters. Atomic charges for retro-inverso modified
      residues were derived from the rigorously calculated quantum mechanical
      electrostatic potential. Furthermore, the reliability of electrostatic models
      based on geometry-dependent charges and fixed charges has been examined.

PMID- 16622794
TI  - Development of small molecules designed to modulate protein-protein interactions.
AB  - Protein-protein interactions are ubiquitous, essential to almost all known
      biological processes, and offer attractive opportunities for therapeutic
      intervention. Developing small molecules that modulate protein-protein
      interactions is challenging, owing to the large size of protein-complex
      interface, the lack of well-defined binding pockets, etc. We describe a general
      approach based on the "privileged-structure hypothesis" [Che, Ph.D. Thesis,
      Washington University, 2003] - that any organic templates capable of mimicking
      surfaces of protein-recognition motifs are potential privileged scaffolds as
      protein-complex antagonists--to address the challenges inherent in the discovery
      of small-molecule inhibitors of protein-protein interactions.

PMID- 16622797
TI  - Prediction of standard Gibbs energies of the transfer of peptide anions from
      aqueous solution to nitrobenzene based on support vector machine and the
      heuristic method.
AB  - Quantitative structure-property relationship (QSPR) method was performed for the
      prediction of the standard Gibbs energies (DeltaGtheta) of the transfer of
      peptide anions from aqueous solution to nitrobenzene. Descriptors calculated from
      the molecular structures alone were used to represent the characteristics of the
      peptides. The four molecular descriptors selected by the heuristic method (HM) in
      COmprehensive DEscriptors for Structural and Statistical Analysis (CODESSA) were
      used as inputs for support vector machine (SVM) and radial basis function neural
      networks (RNFNN). The results obtained by the novel machine learning technique,
      SVM, were compared with those obtained by HM and RBFNN. The root mean squared
      errors (RMS) of the training, predicted and overall data sets are 2.192, 2.541
      and 2.267 unit (kJ/mol) for HM, 1.604, 2.478 and 1.817 unit (kJ/mol) for RBFNN
      and 1.5621, 2.364 and 1.756 unit (kJ/mol) for SVM, respectively. The prediction
      results were in agreement with the experimental values. This paper provided a
      potential method for predicting the physiochemical property (DeltaGtheta) of
      various small peptides.

PMID- 16622798
TI  - Explaining the variance within supported employment programs: comment on "What
      predicts supported employment outcomes?".

PMID- 16622799
TI  - Turbidity mitigates lead toxicity to cladocerans (Cladocera).
AB  - To test the hypothesis that sediment would have a synergistic effect on the
      toxicity of lead to cladocerans, we performed life table demography experiments
      with two pelagic (Diaphanosoma birgei and Moina micrura) and one littoral (Alona
      rectangula) cladoceran species. Life table demography experiments were conducted
      at three levels of turbidity (0, 17 and 170 NTU) and six concentrations of lead
      (as PbCl2) from 0 to 0.71 mg l(-1). Median lethal concentrations (LC50) forA.
      rectangula, D. birgei and M. micrura were 7.06 +/- 0.39, 3.16 +/- 0.25 and 3.24
      +/- 0.69 mg l(-1) of Pb. Life table study showed that in general, the presence of
      sediments in test jars allowed an overall increase of 20-75% in both survivorship
      and reproduction of the cladoceran species exposed to different concentrations of
      Pb. At 0.04 mg l(-1) of Pb, the population growth rates were 0.127 forA.
      rectangula, 0.037 for D. birgei and 0.471 d(-1) for M. micrura in the absence of
      sediments but were elevated in their presence (0.309, 0.141 and 0.722 d(-1),
      respectively). The data have been discussed in relation to their importance in
      shallow, turbid Mexican waterbodies.

PMID- 16622800
TI  - Characterisation by X-ray microanalysis of metal granules in the mucus trails of
      Littorina littorea (Gastropoda) along a putative pollution gradient.
AB  - Metal-containing granules in the mucus trails of the marine gastropod Littorina
      littorea from nine sites in north-east England were analysed for elemental
      composition by X-ray microanalysis and characterised relative to a putative
      gradient of pollution. Overall granule density varied significantly between
      sites, means of 6.5-17.0 per field of view (2688 microm2). Most granules found
      (64%) were poly-metal of a wide variety of compositions, but could be classified
      as Si+X, Mg+X, S+X, Na+X, P+Ca, P+Al, where X indicates any other combination of
      elements. Si+Al+X accounted for 61% of the poly-metal granules found and was
      considered to be contamination from the beach substratum. In single-metal granule
      form only Ca, Si, Fe, Ti, Al and Na were found. The most common single-metal
      granule at each site was of Ca, except at two sites, where the most common single
      metal granule was of Si. The densities of these granule types varied between
      sites but differences were found to be significant only in the case of Si
      granules. Across all sites, single-metal granules of Si (mean = 2.49 microm +/-
      1.44 SD, n = 141) and Ca (2.22 microm +/- 1.08 SD, n = 147) were significantly
      larger than granules of Fe (1.74 microm +/- 0.95 SD, n = 63) and Ti (1.24 microm
      +/- 0.52 SD, n = 18). The range of sizes was large: Ca (0.5-6 microm), Si (0.5-10
      microm), Fe (0.3-4.1 microm), Ti (0.5-2.5 microm). Between the sites there were
      significant differences in the size of Fe and Si granules but not Ca or Ti
      granules. Despite these variations in granule type and size, there was no
      evidence of a relationship with pollution and consequently a detoxifying function
      of the mucus trail in metal polluted environments is not apparent.

PMID- 16622801
TI  - Heavy metal pollution affects consumption and reproduction of the landsnail
      Cepaea nemoralis fed on naturally polluted Urtica dioica leaves.
AB  - This study is one of the very first that investigates the effects of heavy metal
      pollution on food consumption and reproduction of terrestrial snails under semi
      realistic field conditions. Two experiments were carried out using snails (Cepaea
      nemoralis) and food (Urtica dioica leaves) from different metal polluted
      locations and one reference location. The first experiment showed that both
      polluted and reference snails fed on high-metal leaves from a highly polluted
      location had significantly lower consumption rates than snails consuming leaves
      from the reference location. In the second experiment, snails from both locations
      used in the consumption experiment and from two low-polluted locations were kept
      on native soil and food in order to reproduce. No negative effect of heavy metal
      pollution on clutch size was found for the snails from the reference location and
      the low-polluted locations. Snails from the highly polluted location laid no
      eggs. This suggests that at high levels of metal pollution, reproduction is
      strongly negatively affected. We suggest that the absence of egg laying by snails
      from the highly polluted location results from a combination of decreased
      consumption and an increased demand of energy for the accumulation and
      detoxification of metals (decreased scope for growth).

PMID- 16622802
TI  - Heparin-binding epidermal growth factor (HB-EGF) may improve embryonic
      development and implantation by increasing vitronectin receptor (integrin
      alphanubeta3) expression in peri-implantation mouse embryos.
AB  - PURPOSE: This study investigated the effects of HB-EGF on expression of integrin
      alphanubeta3 and implantation of embryos. METHODS: Two-cell embryos were
      recovered and cultured with or without 10 ng/mL HB-EGF for 96h. Expression of
      integrin alphanubeta3 in cultured embryos was examined by real time-RT-PCR and
      immunofluorescence analysis; embryos were cultured with or without HB-EGF, then
      transferred into the uteri of pseudo-pregnant female mice in order to analyze
      their implantation rate. RESULTS: HB-EGF improved embryonic hatching and
      outgrowth during extended culture, and up-regulated expression of integrin
      alphanubeta3 in both the preimplantation embryo and outgrowing blastocyst. Also,
      integrin alphanubeta3 subunits were localized at the pericellular borders and
      cell-cell contact areas. The number of successful implantation sites of
      transferred HB-EGF-treated embryos in the uterus was increased when compared to
      number of implantation sites with non-treated controls. CONCLUSIONS: HB-EGF may
      improve implantation by accelerating expression of integrin alphanubeta3 in peri
      implantation mouse embryos.

PMID- 16622803
TI  - The effect of extended culture of cumulus-oocyte complexes in follicular fluid
      during in vitro fertilisation cycles.
AB  - PURPOSE: To assess the clinical and biological effect of the preincubation of
      oocytes in follicular fluid prior to IVF and ICSI cycles. METHODS: A series of
      patients were treated by the preincubation of oocytes in the patients' follicular
      fluid for 3 h after oocyte retrieval followed by processing with standard
      protocols. Control oocytes were preincubated in normal IVF culture medium.
      Fluorescence techniques were used to examine oocyte mitochondrial membrane
      potential. RESULTS: Fertilisation, pregnancy, and implantation rates were all
      significantly improved after the preincubation of oocytes in follicular fluid.
      Further tests suggested that differences in pH between follicular fluid and
      artificial culture medium may be critical to these differences. CONCLUSIONS:
      Preincubation of human oocytes in follicular fluid improves the results after
      IVF. This may be partly due to the use of a non-"physiological" pH in artificial
      culture media during in vitro fertilisation procedures.

PMID- 16622804
TI  - A prospective randomized trial of conventional in vitro fertilization versus
      intracytoplasmic sperm injection in unexplained infertility.
AB  - PURPOSE: To compare outcomes in patients with unexplained infertility undergoing
      conventional in vitro fertilization (IVF) versus intracytoplasmic sperm injection
      (ICSI). METHODS: Sixty women with unexplained infertility in a Canadian tertiary
      level clinic were randomized to IVF or ICSI. Subjects underwent downregulation
      with gonadotropin-releasing hormone agonist prior to initiation of recombinant
      human follicle-stimulating hormone. The primary outcome measure was fertilization
      rate. Secondary outcomes included implantation rate, embryo quality, clinical
      pregnancy rate, and live birth rate. RESULTS: There was no statistically
      significant difference in fertilization rate (77.2% IVF vs. 82.4% ICSI),
      implantation rate (38.2% IVF vs. 44.4% ICSI), clinical pregnancy rate (50% in
      each group), or live birth rate (46.7% IVF vs. 50% ICSI). There were two cases of
      failed fertilization in the IVF group. There was no significant difference in
      embryo quality between groups. CONCLUSIONS: There were no differences in clinical
      outcomes associated with IVF versus ICSI in the treatment of unexplained
      infertility.

PMID- 16622805
TI  - Association of GABRA2 with drug dependence in the collaborative study of the
      genetics of alcoholism sample.
AB  - Results from twin studies suggest that overlapping genetic factors influence
      alcohol dependence and illicit drug dependence. Using data from the Collaborative
      Study on the Genetics of Alcoholism (COGA), we examined the association between
      69 SNPs in the GABAA receptor gene cluster on chromosome 4 and marijuana and
      illicit drug dependence, individually, and as co-occurring phenotypes with
      alcohol dependence. Results suggested association between marijuana dependence
      and illicit drug dependence with SNPs in the GABRA2 gene. Interestingly, the
      evidence for association previously observed with alcohol dependence came only
      from individuals with comorbid illicit drug dependence. There was no association
      with other genes in the GABAA cluster on chromosome 4 with illicit drug
      dependence.

PMID- 16622807
TI  - In the beginning there was...heat.

PMID- 16622808
TI  - Administrative data fail to accurately identify cases of healthcare-associated
      infection.
AB  - OBJECTIVE: Some policy makers have embraced public reporting of healthcare
      associated infections (HAIs) as a strategy for improving patient safety and
      reducing healthcare costs. We compared the accuracy of 2 methods of identifying
      cases of HAI: review of administrative data and targeted active surveillance.
      DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional prospective study was
      performed during a 9-month period in 2004 at the Children's Hospital of
      Philadelphia, a 418-bed academic pediatric hospital. "True HAI" cases were
      defined as those that met the definitions of the National Nosocomial Infections
      Surveillance System and that were detected by a trained infection control
      professional on review of the medical record. We examined the sensitivity and the
      positive and negative predictive values of identifying HAI cases by review of
      administrative data and by targeted active surveillance. RESULTS: We found
      similar sensitivities for identification of HAI cases by review of administrative
      data (61%) and by targeted active surveillance (76%). However, the positive
      predictive value of identifying HAI cases by review of administrative data was
      poor (20%), whereas that of targeted active surveillance was 100%. CONCLUSIONS:
      The positive predictive value of identifying HAI cases by targeted active
      surveillance is very high. Additional investigation is needed to define the
      optimal detection method for institutions that provide HAI data for comparative
      analysis.

PMID- 16622809
TI  - Sampling for collection of central line-day denominators in surveillance of
      healthcare-associated bloodstream infections.
AB  - OBJECTIVE: To determine the feasibility of estimating the number of central line
      days at a hospital from a sample of months or individual days in a year, for
      surveillance of healthcare-associated bloodstream infections. DESIGN: We used
      data reported to the National Nosocomial Infections Surveillance system in the
      adult and pediatric intensive care unit component for 1995-2003 and data from a
      sample of hospitals' daily counts of device use for 12 consecutive months. We
      calculated the percentile error as the central line-associated bloodstream
      infection percentile based on rates per line-days minus the percentile based on
      rates per estimated line-days. SETTING AND PARTICIPANTS: A total of 247 hospitals
      were used for sampling whole months and 12 hospitals were used for sampling
      individual days. RESULTS: For a 1-month sample of central line-days data, the
      median percentile error was 3.3 (75th percentile, 7.9; 90th percentile, 15.4).
      The percentile error decreased with an increase in the number of months sampled.
      For a 3-month sample, the median percentile error was 1.4 (75th percentile, 4.3;
      95th percentile, 8.3). Sampling individual days throughout the year yielded lower
      percentile errors than sampling an equivalent fraction of whole months. With 1
      weekday sampled per week, the median percentile error ranged from 0.65 to 1.40,
      and the 90th percentile ranged from 2.8 to 5.0. Thus, for 90% of units,
      collecting data on line-days once a week provides an estimate within +/-5
      percentile points of the true line-day rate. CONCLUSION: Sample-based estimates
      of central line-days can yield results that are acceptable for surveillance of
      healthcare-associated bloodstream infections.

PMID- 16622810
TI  - Device-associated nosocomial infection rates in Turkish medical-surgical
      intensive care units.
AB  - OBJECTIVE: To describe the incidence of device-associated nosocomial infections
      in medical-surgical intensive care units (MS ICUs) in a university hospital in
      Turkey and compare it with National Nosocomial Infections Surveillance (NNIS)
      system rates. DESIGN: Prospective surveillance study during a period of 27
      months. Device utilization ratios and device-associated infection rates were
      calculated using US Centers for Disease Control and Prevention and NNIS
      definitions. SETTING: Two separate MS ICUs at Akdeniz University Hospital,
      Antalya, Turkey. PATIENTS: All patients were included who presented with no signs
      and symptoms of infection within the first 48 hours after admission. RESULTS:
      Data on 1,985 patients with a total of 16,892 patient-days were analyzed. The
      mean overall infection rate per 100 patients was 29.1 infections, and the mean
      infection rate per 1,000 patient-days was 34.2 infections. The rate of ventilator
      associated pneumonia was 20.76 infections per 1,000 ventilator-days, the rate of
      catheter-associated urinary tract infection was 13.63 infections per 1,000
      urinary catheter-days, and the rate of catheter-associated bloodstream infection
      was 9.69 infections per 1,000 central line-days. The most frequently isolated
      pathogens were Pseudomonas species among patients with ventilator-associated
      pneumonias (35.8% of cases), Candida species among patients with catheter
      associated urinary tract infections (37.1% of cases), and coagulase-negative
      staphylococci among patients with catheter-associated bloodstream infections
      (20.0% of cases). CONCLUSION: We found both higher device-associated infection
      rates and higher device utilization ratios in our MS ICUs than those reported by
      the NNIS system. To reduce the rate of infection, implementation of infection
      control practices and comprehensive education are required, and an appropriate
      nationwide nosocomial infection and control system is needed in Turkey.

PMID- 16622811
TI  - Device-associated infection rate and mortality in intensive care units of 9
      Colombian hospitals: findings of the International Nosocomial Infection Control
      Consortium.
AB  - OBJECTIVE: To perform active targeted prospective surveillance to measure device
      associated infection (DAI) rates, attributable mortality due to DAI, and the
      microbiological and antibiotic resistance profiles of infecting pathogens at 10
      intensive care units (ICUs) in 9 hospitals in Colombia, all of which are members
      of the International Infection Control Consortium. METHODS: We conducted
      prospective surveillance of healthcare-associated infection in 9 hospitals by
      using the definitions of the US Centers for Disease Control and Prevention
      National Nosocomial Surveillance System (NNIS). DAI rates were calculated as the
      number of infections per 100 ICU patients and per 1,000 device-days. RESULTS:
      During the 3-year study, 2,172 patients hospitalized in an ICU for an aggregate
      duration of 14,603 days acquired 266 DAIs, for an overall DAI rate of 12.2%, or
      18.2 DAIs per 1,000 patient-days. Central venous catheter (CVC)-related
      bloodstream infection (BSI) (47.4% of DAIs; 11.3 cases per 1,000 catheter-days)
      was the most common DAI, followed by ventilator-associated pneumonia (VAP) (32.3%
      of DAIs; 10.0 cases per 1,000 ventilator-days) and catheter-associated urinary
      tract infection (CAUTI) (20.3% of DAIs; 4.3 cases per 1,000 catheter-days).
      Overall, 65.4% of all Staphylococcus aureus infections were caused by methicillin
      resistant strains; 40.0% of Enterobacteriaceae isolates were resistant to
      ceftriaxone and 28.3% were resistant to ceftazidime; and 40.0% of Pseudomonas
      aeruginosa isolates were resistant to fluoroquinolones, 50.0% were resistant to
      ceftazidime, 33.3% were resistant to piperacillin-tazobactam, and 19.0% were
      resistant to imipenem. The crude unadjusted attributable mortality was 16.9%
      among patients with VAP (relative risk [RR], 1.93; 95% confidence interval [CI],
      1.24-3.00; P=.002); 18.5 among those with CVC-associated BSI (RR, 2.02; 95% CI,
      1.42-2.87; P<.001); and 10.5% among those with CAUTI (RR, 1.58; 95% CI, 0.78
      3.18; P=.19). CONCLUSION: The rates of DAI in the Colombian ICUs were lower than
      those published in some reports from other Latin American countries and were
      higher than those reported in US ICUs by the NNIS. These data show the need for
      more-effective infection control interventions in Colombia.

PMID- 16622812
TI  - Device-associated infection rates for non-intensive care unit patients.
AB  - BACKGROUND: Reference data from intensive care units (ICUs) are not applicable to
      non-ICU patients because of the differences in device use rates, length of stay,
      and severity of underlying diseases among the patient populations. In contrast to
      the huge amount of data available for ICU patients, appropriate surveillance data
      for non-ICU patients have been missing in Germany. OBJECTIVE: To establish a new
      module ("DEVICE-KISS") of the German Nosocomial Infection Surveillance System for
      generating stratified reference data for non-ICU wards. SETTING: Non-ICU patients
      from 42 German hospitals. METHODS: Monthly patient-days, device-days and
      nosocomial infections (NIs) (using Centers for Disease Control and Prevention
      definitions) were counted. Device use rates were calculated, and NI rates were
      stratified by different medical specialities. RESULTS: From July 2002 through
      June 2004, among the 77 wards, there were a total of 536,955 patient-days and
      74,188 device-days (for CVC-associated primary bloodstream infections, there were
      181,401 patient-days and 8,317 central vascular catheter [CVC]-days in 29 wards;
      for urinary catheter-associated urinary tract infections, there were 445,536
      patient-days and 65,871 urinary catheter-days in 65 wards) and 483 NIs (36
      bloodstream infections and 447 urinary tract infections). The mean device use
      rates were 4.6 device-days per 100 patient-days for CVCs (29 wards) and 14.8
      device-days per 100 patient-days for urinary catheters (65 wards), respectively.
      Mean device-associated NI rates were 4.3 infections per 1,000 CVC-days for CVC
      associated bloodstream infections and 6.8 infections per 1,000 urinary catheter
      days for catheter-associated urinary tract infections. CONCLUSIONS: DEVICE-KISS
      allows non-ICUs to recognize an outlier position with regard to NIs by providing
      well-founded reference data for non-ICU patients.

PMID- 16622813
TI  - Sustained endemicity of Burkholderia cepacia complex in a pediatric institution,
      associated with contaminated ultrasound gel.
AB  - OBJECTIVE: To determine whether contaminated ultrasound gel is the source of
      intermittent outbreaks of nosocomial infection due to Burkholderia cepacia
      complex in patients without cystic fibrosis since 1992. DESIGN: A prospective
      clinical and in vitro study of all in-use bottles of ultrasound gel, as well as a
      retrospective analysis of archived bacterial strains, were performed. Handling of
      gel for clinical purposes throughout the hospital was evaluated. Gel and archived
      clinical isolates of B. cepacia complex were speciated to genomovar level and
      characterized by pulsed-field gel electrophoresis, and the pulsed-field gel
      electrophoresis patterns were compared. SETTING: The Hospital for Sick Children,
      a 300-bed, tertiary care, pediatric academic health sciences center in Toronto,
      Canada. PATIENTS: All patients without cystic fibrosis from whom B. cepacia
      complex was recovered at the Hospital for Sick Children since 1992. RESULTS: No
      standardized protocol for storage or handling of ultrasound gel was found. Gel
      from 39% of bottles grew either B. cepacia (genomovar I) or Burkholderia stabilis
      (genomovar IV). These isolates had pulsed-field gel electrophoresis patterns
      identical to 2 of the 7 clinical pulsed-field gel electrophoresis types that are
      responsible for 88% of clinical isolates. CONCLUSIONS: Contaminated ultrasound
      gel contributed to nosocomial infection due to B. cepacia complex in this
      institution over the course of 10 years. Suggested guidelines for the handling of
      ultrasound gel are provided.

PMID- 16622814
TI  - Test to determine sterile integrity of wrapped medical products at a probability
      of recontamination of 1 : 1,000,000.
AB  - OBJECTIVE: We developed a microbiological test to detect the penetration of
      airborne microorganisms through the packaging of medical products after
      sterilization, to meet the requirements of European standard EN 556. We applied
      this test method to transparent pouches. DESIGN: The microbial-barrier properties
      of the transparent pouches were determined using the microbial challenge test, in
      which the package was placed inside an exposure chamber and exposed to a defined
      aerosol of Saccharomyces cerevisiae. The atmospheric pressure in the chamber was
      periodically reduced by 0-75 millibars, to simulate weather-dependent pressure
      changes. Thermoresistant petri dishes filled with nutrient agar were integrated
      into the transparent pouches before sterilization. The packages were incubated
      after exposure. They were then opened and examined for colony growth. RESULTS:
      The number of recontaminated packages per test group (n=50) depended on the
      microbial bioload (defined as the number of colony-forming units per plate) to
      which the packages were exposed and on the size and number of decreases in
      atmospheric pressure. Results of multiple regression analysis showed a
      significant increase in the number of recontaminated packages in correlation with
      the product of the values for microbial bioload and the size and number of
      decreases in atmospheric pressure. When we analyzed the probability of
      recontamination of wrapped medical devices after 2 reductions in atmospheric
      pressure (30 millibars each) and with a surface microbial load of 10 colony
      forming units per 64 cm(2), we estimated that the frequency of recontamination
      was 1 : 100,000. CONCLUSION: Multiple regression analysis showed that the
      proposed microbial challenge test is suitable to determine the probability of
      package recontamination at the 1 : 1,000,000 level.

PMID- 16622815
TI  - Bacterial contamination of keyboards: efficacy and functional impact of
      disinfectants.
AB  - BACKGROUND: Computers are ubiquitous in the healthcare setting and have been
      shown to be contaminated with potentially pathogenic microorganisms. This study
      was performed to determine the degree of microbial contamination, the efficacy of
      different disinfectants, and the cosmetic and functional effects of the
      disinfectants on the computer keyboards. METHODS: We assessed the effectiveness
      of 6 different disinfectants (1 each containing chlorine, alcohol, or phenol and
      3 containing quaternary ammonium) against 3 test organisms (oxacillin-resistant
      Staphylococcus aureus [ORSA], Pseudomonas aeruginosa, and vancomycin-resistant
      Enterococcus species) inoculated onto study computer keyboards. We also assessed
      the computer keyboards for functional and cosmetic damage after disinfectant use.
      RESULTS: Potential pathogens cultured from more than 50% of the computers
      included coagulase-negative staphylococci (100% of keyboards), diphtheroids
      (80%), Micrococcus species (72%), and Bacillus species (64%). Other pathogens
      cultured included ORSA (4% of keyboards), OSSA (4%), vancomycin-susceptible
      Enterococcus species (12%), and nonfermentative gram-negative rods (36%). All
      disinfectants, as well as the sterile water control, were effective at removing
      or inactivating more than 95% of the test bacteria. No functional or cosmetic
      damage to the computer keyboards was observed after 300 disinfection cycles.
      CONCLUSIONS: Our data suggest that microbial contamination of keyboards is
      prevalent and that keyboards may be successfully decontaminated with
      disinfectants. Keyboards should be disinfected daily or when visibly soiled or if
      they become contaminated with blood.

PMID- 16622816
TI  - Improving antimicrobial use in the hospital setting by providing usage feedback
      to prescribing physicians.
AB  - OBJECTIVE: To determine whether feedback on antimicrobial use improves physician
      compliance with local hospital guidelines on antimicrobial prescribing. DESIGN:
      In this time series analysis, in which a historical control period was compared
      with an intervention period, all orders for antimicrobials (except those for
      surgical prophylaxis) placed from November 1, 2002, through April 30, 2004, were
      prospectively evaluated by an antimicrobial management team (AMT) for compliance
      with local hospital guidelines. During the control period, orders were evaluated
      to determine compliance with hospital guidelines before and after recommendations
      by the AMT were provided to physicians. Feedback was given for the second 9-month
      period in the form of a weekly report to prescribing physicians, a monthly
      hospital newsletter, and a quarterly report to various hospital committees.
      During the intervention period, orders were evaluated to determine compliance
      with hospital guidelines before and after recommendations by the AMT were
      provided to physicians. SETTING: The Veterans Affairs Medical Center, a 110-bed
      facility, in Louisville, Kentucky. PARTICIPANTS: Internal medicine physicians and
      general surgeons. RESULTS: A total of 2,807 antimicrobial courses were evaluated.
      Compliance with hospital guidelines before AMT recommendations was 70% during the
      control period and 74% during the intervention period (P=.02). Compliance after
      AMT recommendations was 90% during the control period and 93% during the
      intervention period (P< or =.01). CONCLUSION: The use of feedback had a
      significantly favorable impact on physician compliance with the hospital's
      guidelines on antimicrobial prescribing. Use of feedback should be added to the
      list of interventions that promote appropriate antimicrobial use in the hospital
      setting.

PMID- 16622817
TI  - Impact of the 2004-2005 influenza vaccine shortage on immunization practices in
      long-term care facilities.
AB  - OBJECTIVE: To assess the response of long-term care facilities (LTCFs) to the
      2004-2005 influenza vaccine shortage and the impact on resident and healthcare
      worker (HCW) immunization rates. METHODS: A 12-item questionnaire was sent to 824
      randomly selected LTCFs in December 2004. The following 2 open-ended questions
      were also asked: "How did you cope with the vaccine shortage?" and "Who helped
      you get your supply?" Immunization rates reported by LTCF administrators for 2003
      2003 and 2003-2004 were compared with those for 2004-2005. Immunization rates
      were defined as the proportion of all eligible residents and HCWs who received
      influenza vaccine. RESULTS: Responses were received from 380 LTCFs (46.3%), which
      had a total of 38,447 beds. Resident mean influenza immunization rates (+/-SD)
      decreased from 85%+/-15.3% in 2002-2003 and 85.1%+/-15.3% in 2003-2004 to 81.9%+/
      19.4% in the 2004-2005 influenza season (P=.025). The immunization rates among
      HCWs also decreased from 51% in 2002-2003 and 2003-2004 to 38.4% in 2004-2005
      (P<.001). In response to one of the open-ended questions, 96 facilities (25.3%)
      reported that they obtained vaccine from 2 or more sources. Eight percent
      commented on specific intensified infection control efforts, and only 2.3%
      commented on emergency preparedness. CONCLUSIONS: The influenza vaccine shortage
      in 2004-2005 impacted immunization practices of LTCFs across the United States,
      leading to decreases in both resident and HCW vaccination rates. The significant
      decrease in vaccination rates in LTCFs is of concern and has broad implications
      for policy makers working on emergency preparedness for a possible pandemic of
      influenza.

PMID- 16622818
TI  - Influenza immunization in nursing homes: who does not get immunized and whose
      status is unknown?
AB  - OBJECTIVE: To identify nursing home resident and facility characteristics
      associated with patients not receiving influenza immunization and having unknown
      immunization status. DESIGN: Secondary data analysis using multinomial logistic
      regression of data from the National Nursing Home Survey, a nationally
      representative establishment-based survey. SETTING: A total of 1,423 nursing
      facilities of all ownerships and certifications systematically sampled with
      probability proportional to number of beds. PATIENTS: A total of 7,350 randomly
      sampled people aged 65 years or older residing in nursing homes between July and
      December 1999 (approximately 6 per facility). MAIN OUTCOME MEASURE: Immunization
      status of residents. RESULTS: Fifteen percent of residents were not immunized and
      19% had unknown immunization status. In multivariate analysis, lack of
      immunization and unknown immunization status were each separately associated with
      being newly admitted, with no or unknown pneumococcal immunization, and with
      facility failures to screen for immunization and to record inoculation in the
      medical record. High-risk status and staff immunization requirements had no
      effect. Separate analyses showed that residents with unknown immunization status
      are statistically significantly different from both those vaccinated and those
      not vaccinated. CONCLUSION: This study indicates that both resident and facility
      characteristics are associated with failure to be immunized for influenza.
      Facilities should consider targeting younger, newly admitted, and residential
      care residents for influenza immunization, since they are more likely to be
      missed. Further research into the barriers to immunization specific to nursing
      home resident choice or opportunity may be warranted.

PMID- 16622819
TI  - Outbreak of infection with Acinetobacter strain RUH 1139 in an intensive care
      unit.
AB  - OBJECTIVE: To investigate a nosocomial outbreak of infection with Acinetobacter
      strain RUH 1139, in the unit of high neonatal risk at University Hospital of The
      Andes (Merida, Venezuela). METHODS: Twenty-eight Acinetobacter strains were
      detected by biochemical testing and further identified to the species level by
      examination of the gene encoding 16S ribosomal DNA, using restriction analysis
      and gene sequencing. The epidemiological relationship between the strains was
      established by means of repetitive extragenic palindromic polymerase chain
      reaction (REP-PCR) and pulsed-field gel electrophoresis (PFGE), and antimicrobial
      susceptibilities were determined by disk diffusion. RESULTS: The spread of an
      epidemic strain of Acinetobacter RUH 1139 among 16 patients over a period of 3
      months was demonstrated using antimicrobial susceptibility testing, PFGE, and REP
      PCR. The epidemic strain was also isolated in 2 of the sampled parenteral
      nutrition solutions. All the patients involved in the infection outbreak had
      received parenteral solution. Moreover, strains of Acinetobacter RUH 1139 with
      another PFGE pattern and of A. baumannii were sporadically isolated before and
      during the outbreak. CONCLUSION: This is the first description of an outbreak of
      infection with this genospecies of Acinetobacter in which parenteral nutrition
      solution was potentially the infection source.

PMID- 16622820
TI  - Epidemiology of Acinetobacter baumannii in a university hospital in Turkey.
AB  - OBJECTIVE: Molecular epidemiologic surveillance of Acinetobacter baumannii by
      polymerase chain reaction-randomly amplified polymorphic DNA analysis in a
      university hospital for 3 consecutive study periods. RESULTS: Twelve different
      Acinetobacter baumannii genotypes (A-L) were detected. Although only 2 genotypes
      were detected during the first period and genotype A appeared to be the most
      common genotype, genotype D was included in these genotypes during the second
      study period. Genotype A completely disappeared during the third period. Although
      the presence of genotype C and the genotype D continued during the third period,
      9 new genotypes were detected during this period. Genotype A appeared to be the
      most common genotype in the hospital (detected in 19 different clinics). The
      distribution of genotypes in clinical samples correlated with patient traffic
      between them. Some genotypes were found in both clinical and environmental
      samples. Seventeen different antibiotypes were detected, according to antibiotic
      susceptibility profiles. CONCLUSIONS: Environmental contamination, airborne
      transmission, patient transfer, and cross-contamination play important roles in
      epidemics caused by A. baumannii in our hospital. The distribution of genotypes
      can change over time, so antibiotyping is not appropriate for the epidemiological
      analysis of A. baumanii infection.

PMID- 16622821
TI  - Analysis and presentation of cumulative antimicrobial susceptibility data
      (antibiograms): substantial variability across medical centers in the United
      States.
AB  - We found substantial variability in approaches to constructing antibiograms at 65
      United States medical centers. Laboratories in teaching hospitals and those with
      more personnel were significantly more likely to offer sophisticated antibiogram
      approaches, including the compiling of unit-specific susceptibility data and the
      reporting of temporal trends in susceptibility data.

PMID- 16622822
TI  - Identification of optimal combinations for empirical dual antimicrobial therapy
      of Pseudomonas aeruginosa infection: potential role of a Combination Antibiogram.
AB  - To better determine the optimal combinations for empirical dual antimicrobial
      therapy of Pseudomonas aeruginosa infection, we evaluated the utility of a novel
      combination antibiogram. Although the combination antibiogram allowed modest fine
      tuning of choices for dual antibiotic therapy, selections based on the 2
      antibiograms did not differ substantively. Drug combinations with the broadest
      coverage were consistently composed of an aminoglycoside and a beta-lactam.

PMID- 16622823
TI  - Inappropriate antibiotic use in a tertiary care center in Thailand: an incidence
      study and review of experience in Thailand.
AB  - The incidence and patterns of and factors associated with inappropriate
      antibiotic use were studied in a tertiary care center in Thailand. The incidence
      of inappropriate antibiotic use was 25%. Admission to the surgical department
      (adjusted odds ratio, 2.0; P=.02) and to the obstetrics and gynecology department
      (adjusted odds ratio, 2.0; P=.03) were associated with inappropriate antibiotic
      use, whereas consultation with an infectious diseases specialist was protective
      against inappropriate antibiotic use (adjusted odds ratio, 0.15; P=.01).

PMID- 16622824
TI  - Prevalence of nosocomial infections in high-risk units in the university clinical
      center of Kosova.
AB  - A point-prevalence study was performed to determine the prevalence of nosocomial
      infections in University Clinical Center of Kosova. Of 167 surveyed patients, 27
      had a total of 29 nosocomial infections, with an overall prevalence rate of
      17.4%. Nosocomial bloodstream infections were most prevalent (62%). The
      prevalence was highest among neonates in intensive-care units (77.8%).

PMID- 16622825
TI  - Pyrogenic reactions in hemodialysis patients, Hanoi, Vietnam.
AB  - Of 33,111 patients admitted to a large hospital in Vietnam from November 2000
      through July 2001, a total of 303 were undergoing hemodialysis and had pyrogenic
      reactions (ie, fever and/or rigors). Ten case patients (3.3%) had documented
      bacteremia; pathogens were largely waterborne microorganisms. Pyrogenic reactions
      in case patients might have occurred because of suboptimal water quality or
      inadequate dialyzer reprocessing procedures.

PMID- 16622826
TI  - Three uses of the standardized infection ratio (SIR) in infection control.

PMID- 16622827
TI  - Exploring structural requirements for aldose-reductase inhibition by 2,4-dioxo-5
      (naphth-2-ylmethylene)-3-thiazolidinyl acetic acids and 2-thioxo analogues:
      Fujita-Ban and Hansch approach.
AB  - A Quantitative Structure-Activity Relationship (QSAR) study based on Fujita-Ban
      and classical Hansch approach was performed on 2,4-dioxo-5-(naphth-2-ylmethylene)
      3-thiazolidinyl acetic acids and 2-thioxo analogues to gain structural insight
      into the binding mode of the molecules to the aldose-reductase enzyme. First, the
      Fujita-Ban approach has been followed, which revealed the highest activity
      contribution for 2-thioxo analogues of 3-thiazolidinyl acetic acids as compared
      to 2,4-dioxo analogues. Further, the Hansch approach confirms that 2-thioxo-4-oxo
      3-thiazolidinyl acetic acids are conducive to aldose-reductase inhibitory
      activity. The hydrophobic properties of the various substituents have been found
      to play major roles in the binding of these compounds with the receptor.

PMID- 16622828
TI  - Mediterranean diet and risk for Alzheimer's disease.
AB  - OBJECTIVE: Previous research in Alzheimer's disease (AD) has focused on
      individual dietary components. There is converging evidence that composite
      dietary patterns such as the Mediterranean diet (MeDi) is related to lower risk
      for cardiovascular disease, several forms of cancer, and overall mortality. We
      sought to investigate the association between MeDi and risk for AD. METHODS: A
      total of 2,258 community-based nondemented individuals in New York were
      prospectively evaluated every 1.5 years. Adherence to the MeDi (zero- to nine
      point scale with higher scores indicating higher adherence) was the main
      predictor in models that were adjusted for cohort, age, sex, ethnicity,
      education, apolipoprotein E genotype, caloric intake, smoking, medical
      comorbidity index, and body mass index. RESULTS: There were 262 incident AD cases
      during the course of 4 (+/-3.0; range, 0.2-13.9) years of follow-up. Higher
      adherence to the MeDi was associated with lower risk for AD (hazard ratio, 0.91;
      95% confidence interval, 0.83-0.98; p=0.015). Compared with subjects in the
      lowest MeDi tertile, subjects in the middle MeDi tertile had a hazard ratio of
      0.85 (95% confidence interval, 0.63-1.16) and those at the highest tertile had a
      hazard ratio of 0.60 (95% confidence interval, 0.42-0.87) for AD (p for
      trend=0.007). INTERPRETATION: We conclude that higher adherence to the MeDi is
      associated with a reduction in risk for AD.

PMID- 16622829
TI  - Comparative proteomics of glycosomes from bloodstream form and procyclic culture
      form Trypanosoma brucei brucei.
AB  - Peroxisomes are present in nearly every eukaryotic cell and compartmentalize a
      wide range of important metabolic processes. Glycosomes of Kinetoplastid
      parasites are peroxisome-like organelles, characterized by the presence of the
      glycolytic pathway. The two replicating stages of Trypanosoma brucei brucei, the
      mammalian bloodstream form (BSF) and the insect (procyclic) form (PCF), undergo
      considerable adaptations in metabolism when switching between the two different
      hosts. These adaptations involve also substantial changes in the proteome of the
      glycosome. Comparative (non-quantitative) analysis of BSF and PCF glycosomes by
      nano LC-ESI-Q-TOF-MS resulted in the validation of known functional aspects of
      glycosomes and the identification of novel glycosomal constituents.

PMID- 16622830
TI  - A simple and rapid protein array based method for the simultaneous detection of
      biowarfare agents.
AB  - A protein chip has been developed that allows the simultaneous detection of a
      multitude of different biowarfare agents. The chip was developed for the
      ArrayTube platform providing a cheap and easy to handle technology solution that
      combines a microtube-integrated protein chip with the classical procedure of a
      sandwich-enzyme-linked immunosorbent assay and signal amplification by
      streptavidin-poly-horseradish peroxidase. Specific immunoassays for
      Staphylococcus enterotoxin B, ricin, Venezuelan equine encephalitis virus, St.
      Louis encephalitis virus, West Nile virus, Yellow fever virus, Orthopox virus
      species, Francisella tularensis, Yersinia pestis, Brucella melitensis,
      Burkholderia mallei and Escherichia coli EHEC O157:H7 were developed and
      optimized. All assays could be completed within 1 to 1 1/2 h and detection levels
      were demonstrated to be as low as in well established ELISAs. Most interesting,
      as a result of careful antibody screening and testing, it is currently possible
      to analyse at least five of the "dirty dozen" agents on one single protein chip
      in parallel.

PMID- 16622831
TI  - Proteins differentially expressed in response to nicotine in five rat brain
      regions: identification using a 2-DE/MS-based proteomics approach.
AB  - To determine protein expression patterns within the central nervous system (CNS)
      in response to nicotine, 2-DE/MS was performed on samples from five brain regions
      of rats that had received nicotine bitartrate by osmotic minipump infusion at a
      dose of 3.15 mg/kg/day for 7 days. After spot matching and statistical analysis,
      41 spots in the amygdala, 49 in the nucleus accumbens (NA), 46 in the prefrontal
      cortex (PFC), 36 in the striatum, and 28 in the ventral tegmental area (VTA)
      showed significant differences in the nicotine-treated compared with control
      samples. Using MALDI-TOF MS peptide fingerprinting, 14 proteins in the amygdala,
      11 in the NA, 19 in the PFC, 13 in the striatum, and 19 in the VTA were
      identified. Several proteins (e.g. dynamin 1, laminin receptors, aldolase A,
      enolase 1 alpha, Hsc70-ps1, and N-ethylmaleimide-sensitive fusion protein) were
      differentially expressed in multiple brain regions. By gene ontology analysis,
      these differentially expressed proteins were grouped into biological process
      categories, such as energy metabolism, synaptic function, and oxidative stress
      metabolism. These data, in combination with microarray analysis of mRNA
      transcripts, have the potential to identify the CNS gene products that show
      coordinated changes in expression at both the RNA and protein levels in response
      to nicotine.

PMID- 16622832
TI  - Proteomic changes in hearts of kyphoscoliosis (ky) mutant mice in the absence of
      structural pathology: implication for the analysis of early human heart disease.
AB  - Complex molecular changes associated with early stage human heart disease are
      poorly understood and prevent the development of effective treatments of human
      cardiac disease. Relatively minor structural changes in early disease may
      accompany some conditions such as arrhythmias. Our objective was to determine if
      significant proteomic changes occur in heart tissues in the absence of structural
      pathology. We used a proteomic "pipeline" based on Ciphergen SELDI-TOF/MS, gel
      electrophoresis and MALDI-TOF/MS. The kyphoscoliosis (ky) mouse carries a
      mutation in a putative transglutaminase causing a primary skeletal muscle
      disease. The ky protein is expressed usually in skeletal and cardiac muscle but
      its absence from the ky heart causes no structural pathology making it a good
      model of "occult" heart disease. We discovered 20 statistically validated
      biomarkers discriminating ky from normal hearts, one cardiac troponin-I was
      reduced by 40% in ky hearts. A 17% deficit was confirmed subsequently by Western
      blot. Thus, the proteome of ky hearts was abnormal, giving support to our
      contention that this SELDI-based analytical approach is capable of making a
      significant contribution to the analysis of complex proteomic changes in early
      stage human heart disease.

PMID- 16622833
TI  - Comprehensive glyco-proteomic analysis of human alpha1-antitrypsin and its charge
      isoforms.
AB  - Human alpha1-antitrypsin (A1PI) is a well-known glycoprotein in human plasma
      important for the protection of tissues from proteolytic enzymes. The three N
      glycosylation sites of A1PI contain diantennary N-glycans but also triantennary
      and even traces of tetraantennary structures leading to the typical IEF pattern
      observed for A1PI. Here we present an approach to characterize A1PI isoforms from
      human plasma and its PTMs by LC-ESI-MS and LC-ESI-MS/MS of peptides obtained by
      proteolytic digestion. The single cysteine residue of A1PI formed a disulfide
      bridge with free cysteine. The variability of the number of antennae and hence
      sialic acids on glycosylation site N107, which even contained minute amounts of
      tetraantennary structures, emerged as a major cause for the IEF pattern of A1PI.
      Only negligible amounts of triantennary structures were identified attached to
      N70, and exclusively diantennary structures were present on site N271 in each of
      the isoforms analyzed. Exoglycosidase digests revealed alpha2,6-linked neuraminic
      acids on diantennary N-glycans, and triantennary contained additionally one
      single alpha2,3-neuraminic acid per N-glycan, which, together with a fucose,
      formed a sialyl Lewis X determinant on the beta1,4-linked N-acetylglucosamine, as
      shown by 2-D-HPLC of pyridylaminated asialoglycans. Fucosylation of diantennary
      structures was marginal and of the core alpha1,6 type.

PMID- 16622834
TI  - In vitro culture conditions favoring selection of chromosomal abnormalities in
      human ES cells.
AB  - Previous studies in several laboratories have demonstrated inadvertent
      chromosomal abnormalities in long-term cultured human embryonic stem cells
      (HESC). Here, using a two-step selection process we report a functional
      adaptation of a HESC line, HS181, towards a decreased dependence of extra
      cellular matrix (ECM) for in vitro survival, that is for growth directly onto a
      plastic surface. Successful adaptation was paralleled with a karyotype change in
      100% of the cells to 47,XX,del(7)(q11.2),+i(12)(p10). The resulting adapted
      population showed increased survival and growth on plastic and also maintained
      expression of HESC markers, but showed a decreased pluripotency, as demonstrated
      by results from embryoid body (EB) formation in vitro. The finding of reduced
      pluripotency may not be totally unexpected since the variant cells were selected
      for self-renewal and proliferation, not differentiation during the adaptation to
      growth on plastic. In the light of recent models of a germ cell origin of HESC it
      is of particular interest that similar to many of the reported spontaneous HESC
      mutants, one of the identified specific chromosome abnormalities, i(12p), has
      also been strongly implicated for human germ cell cancer. However, the mutated
      HESC variant carrying this mutation failed to grow as a xeno-graft in a mouse
      model in vivo. This is surprising and needs a further mechanistic analysis for
      its explanation. Increased knowledge of genetic integrity of HESC may have
      significance on the understanding of mechanisms for tumor progression and thus
      strategy for treatments, particularly for tumors occurring in early life.

PMID- 16622835
TI  - Comparative proteomic analysis of hypoxia-treated and untreated human leukemic
      U937 cells.
AB  - We reported recently that moderate hypoxia and hypoxia-mimetic agents could
      induce growth arrest and differentiation of leukemic cells via the mediation of
      hypoxia-inducible factor 1 alpha (HIF-1alpha), but the exact molecular mechanisms
      remain largely unknown. In this study, human acute promonocytic leukemic U937
      cells were incubated under 2% O2 or in 50 microM of the hypoxia mimetic agent
      cobalt chloride (CoCl2) and normal oxygen for 24 h, and their protein expression
      profiles were compared by 2-DE coupled with MALDI-TOF/TOF MS/MS. We identified 62
      and 16 proteins that were significantly deregulated by hypoxia and CoCl2
      treatment, respectively. These proteins were mainly involved in metabolism, gene
      expression regulation, signal transduction, cell proliferation, differentiation
      and apoptosis. As an example, N-myc downstream regulated gene 1 (NDRG1), a
      putative differentiation-related gene, was up-regulated in both 2% O2- and CoCl2
      treated U937 cells. Moreover, enforced HIF-1alpha expression also elevated NDRG1
      mRNA and protein in U937 cells. These data will provide some clues for
      understanding mechanisms by which leukemic cells response to hypoxia.

PMID- 16622836
TI  - The plasma membrane proteome of Saccharomyces cerevisiae and its response to the
      antifungal calcofluor.
AB  - Calcofluor is an antifungal compound known to induce structural perturbations of
      the cell wall by interfering with the synthesis of chitin microfibril. Proteins
      from a stripped plasma membrane fraction were solubilized with the neutral and
      non-denaturing detergent, the n-dodecyl beta-D-maltoside. Proteins were then
      resolved using a recently described ion-exchange chromatography (IEC)/lithium
      dodecyl sulfate (LDS)-PAGE procedure. Nearly 90 proteins were identified and
      clustered, based on their pI, molecular weight, abundance and/or hydrophobicity.
      This method was then applied to profile the plasma membrane response to
      calcofluor. The LDS-PAGE patterns obtained from whole plasma membrane proteins
      were similar for the non-treated and calcofluor-treated samples. However, IEC/LDS
      PAGE analysis revealed subtle changes in the expression of several proteins of
      low abundance, in response to calcofluor. These proteins include Pil1p and Lsp1p,
      two sphingolipid long-chain base-responsive inhibitors of protein kinases
      involved in signaling pathways for cell wall integrity and Rho1p, a small GTPase.
      It was recently hypothesized that Pil1p and Lsp1p could associate with, and
      regulate, the plasma membrane beta-1-3-glucan synthase, responsible for the
      synthesis of another major microfibril for yeast cell wall. Results are discussed
      with respect to both calcofluor effects on the plasma membrane proteins and the
      power of the IEC/LDS-PAGE procedure in the search for new potential therapeutics
      targets.

PMID- 16622837
TI  - Proteomic analysis of rat pheochromocytoma PC12 cells.
AB  - PC12 cell line is well documented and widely applied as many kinds of models in
      neurobiological and neurochemical studies. Yet a thorough proteomic analysis has
      not been performed so far. Here we report the construction of a large-scale 2-D
      protein database for PC12 cells. The proteins extracted from PC12 cells were
      separated by 2-DE and identified by MALDI-TOF/TOF MS. A total of 1080 protein
      spots, excised from three different 2-D gels, were identified with high
      confidence. These proteins represent 474 different gene products, mainly binding
      proteins and enzymes. Three hundred and seven identified protein spots were
      located in the low-molecular weight region below 20 kDa. This database today
      represents one of the largest 2-D databases for higher eukaryotic cell proteomes
      and for low-molecular weight proteins. In addition, fragment ion spectra obtained
      by TOF/TOF confirmed that calcylin in PC12 cells was N-acetylated. The database
      of PC12 proteome is expected to be a powerful tool for neuroscientists.

PMID- 16622838
TI  - Proteomic analysis of liver tissues subjected to early ischemia/reperfusion
      injury during human orthotopic liver transplantation.
AB  - Knowledge of early molecular events occurring upon ischemia/reperfusion (I/R)
      during liver transplantation (LT) is of great importance to improve the
      therapeutic intervention of surgical treatment. However, nowadays, few data are
      available on early protein targets of I/R injury. To identify these proteins, we
      used a differential proteomics approach in the characterization human liver
      biopsies during I/R upon LT. Analyses were performed on nine donor livers during
      LT. By using 2-DE and MALDI-TOF MS, we identified 36 proteins which resulted
      significantly altered upon I/R injury. The majority of these proteins are
      functionally involved in lipid and energy metabolism, in different metabolic
      pathways, in redox signalling and in oxidative-stress response. Our data
      represent the first global approach in the study of I/R injury in liver.

PMID- 16622839
TI  - Identification of crystallin family proteins in vitreous body in rat endotoxin
      induced uveitis: Involvement of crystallin truncation in uveitis pathogenesis.
AB  - Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation.
      To characterize the mechanism of EIU, we analyzed the infiltration of proteins in
      the vitreous bodies of rats with EIU and normal rats using 2-DE and micro LC/LC
      MS/MS. Twenty spots were identified in vitreous bodies of rats. Eighteen of these
      spots were members of the crystallin family. The truncated form of beta A4- and
      beta B2-crystallin were predominant in normal vitreous bodies, but there were
      intact form of crystallins in lipopolysaccharide-injected rats with EIU. These
      results suggest that crystallin family proteins are the major group of proteins
      involved in uveitic vitreous and that C-terminal truncation of beta-crystallins
      may play a role in EIU-related disease progression.

PMID- 16622840
TI  - PAI-1 transcriptional regulation during the G0 --> G1 transition in human
      epidermal keratinocytes.
AB  - Plasminogen activator inhibitor type-1 (PAI-1) is the major negative regulator of
      the plasmin-dependent pericellular proteolytic cascade. PAI-1 gene expression is
      normally growth state regulated but frequently elevated in chronic
      fibroproliferative and neoplastic diseases affecting both stromal restructuring
      and cellular migratory activities. Kinetic modeling of cell cycle transit in
      synchronized human keratinocytes (HaCaT cells) indicated that PAI-1 transcription
      occurred early after serum stimulation of quiescent (G0) cells and prior to entry
      into a cycling G1 condition. PAI-1 repression (in G0) was associated with
      upstream stimulatory factor-1 (USF-1) occupancy of two consensus E box motifs (5'
      CACGTG-3') at the PE1 and PE2 domains in the PF1 region (nucleotides -794 to 
      532) of the PAI-1 promoter. Chromatin immunoprecipitation (ChIP) analysis
      established that the PE1 and PE2 site E boxes were occupied by USF-1 in quiescent
      cells and by USF-2 in serum-activated, PAI-1-expressing keratinocytes. This
      reciprocal and growth state-dependent residence of USF family members (USF-1 vs.
      USF-2) at PE1/PE2 region chromatin characterized the G0 --> G1 transition period
      and the transcriptional status of the PAI-1 gene. A consensus E box motif was
      required for USF/E box interactions, as a CG --> AT substitution at the two
      central nucleotides inhibited formation of USF/probe complexes. The 5' flanking
      sites (AAT or AGAC) in the PE2 segment were not necessary for USF binding. USF
      recognition of the PE1/PE2 region E box sites required phosphorylation with
      several potential involved residues, including T153, maping to the USF-specific
      region (USR). A T153A substitution in USF-1 did not repress serum-induced PAI-1
      expression whereas the T153D mutant was an effective suppressor. As anticipated
      from the ChIP results, transfection of wild-type USF-2 failed to inhibit PAI-1
      induction. Collectively, these data suggest that USF family members are important
      regulators of PAI-1 gene control during serum-stimulated recruitment of quiescent
      human epithelial cells into the growth cycle.

PMID- 16622841
TI  - Caregiving time in sickle cell disease: psychological effects in maternal
      caregivers.
AB  - BACKGROUND: Providing home care for a child with a chronic illness can be
      stressful for the family. The purpose of this paper is to examine patterns of
      caregiving and the associated psychological impact on maternal caregivers of
      children with sickle cell disease (SCD). PROCEDURE: Fourteen maternal caregivers
      of children with SCD were interviewed as part of a larger study of maternal
      caregivers of children with chronic illness. Forty-four caregivers of children
      with HIV and 36 caregivers of healthy children were included as comparison
      groups. Interviews included questions regarding amount of time spent providing
      care for the child (technical care, non-technical care, health care management),
      hospitalization, emergency room visits, illness stigma, and mental health of the
      caregiver. RESULTS: Children with SCD had significantly lower functional status
      and significantly more hospitalizations in the previous 3 months than children
      with HIV. Caregivers of children with SCD were more likely to work full-time and
      had higher incomes than caregivers of children with HIV. The three caregiving
      groups did not differ significantly on amount of total care, although caregivers
      of children with SCD and caregivers of children with HIV both reported
      significantly more time spent in technical care than caregivers of healthy
      children. Despite lower functional status of the children in the SCD group, when
      group comparisons on caregiving time variables were adjusted for child's
      functional status, the differences between groups increased. This appeared to be
      due to the fact that caregivers in the HIV group spent more time in all
      caregiving categories except skin, crisis, and other care. In terms of caregiver
      mental health, caregivers of children with HIV and SCD had significantly higher
      depressive mood scores than caregivers of healthy children but the groups did not
      differ on caregiving burden. CONCLUSIONS: The perceived care burden of caregivers
      of children with SCD may be related to the unpredictable nature of the crisis
      care they provide. Additional attention is warranted to developing adequate
      resources for caregivers of children with SCD to mitigate the stress of
      unexpected crises.

PMID- 16622842
TI  - Crystallization of sucrose glass under ambient conditions: evaluation of
      crystallization rate and unusual melting behavior of resultant crystals.
AB  - Isothermal crystallization of sucrose glass under ambient condition was
      investigated by powder X-ray diffraction, isothermal microcalorimetry, and water
      sorption/desorption analysis. Isothermal microcalorimetry measurements showed
      that the crystallization behavior was affected by the compression force applied
      to starting amorphous materials. The crystallization rate was analyzed by X-ray
      diffraction measurements to establish that the rate could well be explained by
      the Avrami-Erofeev equation. In the water sorption/desorption analysis, the
      weight change during the crystallization was elucidated by supposing that
      desorption proceeded from the crystallized part. The sucrose crystallized at
      relatively low temperature conditions showed completely different melting
      behavior from that of intact sucrose, although the crystal form was most likely
      to be identical. This difference could be explained by defects in the lattice
      structure produced during the crystallization and the desorption process.
      Correlation was found between the melting temperature and the water content just
      before the crystallization. Defects in the crystal structure were partially
      modified by annealing as has been found in relaxation studies of amorphous
      materials.

PMID- 16622844
TI  - Efficacy, predictors of response, and potential risks associated with antiviral
      therapy in liver transplant recipients with recurrent hepatitis C.
AB  - There are unresolved issues regarding sustained virological response (SVR),
      tolerance and risk of rejection following antiviral therapy in liver
      transplantation (LT). The aim of our study was to determine efficacy, rejection
      risk and factors associated with SVR. HCV-infected LT patients with at least 6
      months of follow-up following end-of-therapy (EOT) received combination therapy
      of ribavirin (Rbvr) + standard (n = 31)/pegIFN (n = 36) between 1999 and 2004
      (95% genotype 1). An EOT and SVR was obtained in 46% and 33%, respectively. Type
      of antiviral therapy, use of erythropoietin, compliance, and early virologic
      response (EVR) were predictive of SVR, but only the latter remained in the
      multivariate analysis. Premature discontinuation, not impacted by the use of
      erythropoietin or GCSF, occurred in 40% patients. None of the variables predicted
      rejection (acute n = 2, chronic n = 4). A SVR occurred in 3/4 patients with
      chronic rejection. In conclusion, the efficacy of pegIFN-Rbvr is similar to the
      non-transplant population. An EVR at 3 months is useful to predict lack of
      response. The type of calcineurin inhibitor and history of prior non-response to
      IFN before LT do not influence the outcome of therapy. Severe rejection may lead
      to graft loss, a complication difficult to predict.

PMID- 16622845
TI  - Matrix metalloproteinases in development and disease.
AB  - Matrix metalloproteinases (MMPs) are key modulators of many biological processes
      during pathophysiological events, such as skeletal formation, angiogenesis,
      cellular migration, inflammation, wound healing, coagulation, lung and
      cardiovascular diseases, arthritis, and cancer. Twenty-four members of the MMP
      family have been identified in humans, degrading many components of the
      extracellular matrix, cellular receptors, and cytokines. This review describes
      the molecular structure, activation and inhibition, and substrate specificity of
      MMPs, and their biological function in development and disease.

PMID- 16622846
TI  - Aspects of extracellular matrix remodeling in development and disease.
AB  - The extracellular matrix is the major constituent of organic matter in both
      plants and animals, where it provides the interface between individual cells. In
      most tissues, with some notable exceptions such as bone marrow, the volume of
      extracellular matrix equals or exceeds the volume of intracellular space and
      organelles, making matrix an abundant constituent through which cells exert their
      functions and receive cues. The matrix may therefore be considered the basic
      structural entity that supports the function of an organ, and in connective
      tissues the matrix is the organ itself to which function is tied throughout the
      life of its resident cells. In this review, a select number of proteinases
      involved in some of the more conspicuous matrix remodeling events of the
      mammalian organism are explored. Evidence from both animal models and human
      diseases is discussed in relation to normal physiological processes, including
      instances in which aberrant matrix remodeling leads to disease states.

PMID- 16622847
TI  - (Make) stick and cut loose--disintegrin metalloproteases in development and
      disease.
AB  - "A disintegrin and metalloprotease" (ADAM) proteases form a still growing family
      of about 40 type 1 transmembrane proteins. They are defined by a common modular
      ectodomain architecture that combines cell deadhesion/adhesion and fusion motifs
      (disintegrin and cysteine-rich domains), with a Zn-protease domain capped by a
      large prodomain. Their ectodomain thus strikingly resembles snake venom
      disintegrin proteases, which by combined integrin blocking and extracellular
      proteolysis, can cause extensive tissue damage after snake bites. A surprisingly
      large proportion (13 ADAMs) is exclusively expressed in the male gonads, and only
      a minority can be found throughout all tissues. As predicted by their amino acid
      sequence, a major proportion of this family has not maintained a functional
      protease domain, most probably rendering them into pure adhesion and/or fusion
      proteins. For most ADAMs, the respective key function has remained elusive.
      Despite their overall conserved ectodomain structure, ADAMs appear to be
      subdivided into those with a predominant role in direct adhesion (e.g., ADAMs 1,
      2, and 3) and those mainly acting as proteases (e.g., ADAMs 10 and 17). Only for
      a few of them are functions of more than one domain documented (e.g., ADAM9 in
      cell fusion and proteolysis). Several ADAMs exist in both membrane-resident and
      secreted isoforms; the functional significance of this dichotomy is in most cases
      still unclear. Knockout phenotypes have been informative only in a few cases
      (ADAMs 1, 2, 10, 12, 15, 17, and 19) and are mainly related to their protease
      function. A common denominator of ADAM-mediated proteolysis is the ectodomain
      shedding of a broad spectrum of substrates, including paracrine growth factors
      like epidermal growth factor receptor (EGFR) ligands, cell adhesion molecules
      like CD44 or cadherins, and the initiation of regulated intramembrane proteolysis
      (RIP), whereby the transmembrane fragment of the respective substrate is further
      cleaved by an intramembrane cleaving protease to release an intracellular domain
      acting as a nuclear transcription regulator. Most ADAMs feature a significant
      overlap of substrate specificities, explaining why an inactivation of individual
      ADAMs only rarely causes major phenotypes.

PMID- 16622848
TI  - Developmental roles of the BMP1/TLD metalloproteinases.
AB  - The astacin family (M12A) of the metzincin subclan MA(M) of metalloproteinases
      has been detected in developing and mature individuals of species that range from
      hydra to humans. Functions of this family of metalloproteinase vary from
      digestive degradation of polypeptides, to biosynthetic processing of
      extracellular proteins, to activation of growth factors. This review will focus
      on a small subgroup of the astacin family; the bone morphogenetic protein 1
      (BMP1)/Tolloid (TLD)-like metalloproteinases. In vertebrates, the BMP1/TLD-like
      metalloproteinases play key roles in regulating formation of the extracellular
      matrix (ECM) via biosynthetic processing of various precursor proteins into
      mature functional enzymes, structural proteins, and proteins involved in
      initiating mineralization of the ECM of hard tissues. Roles in ECM formation
      include: processing of the C-propeptides of procollagens types I-III, to yield
      the major fibrous components of vertebrate ECM; proteolytic activation of the
      enzyme lysyl oxidase, necessary to formation of covalent cross-links in collagen
      and elastic fibers; processing of NH2-terminal globular domains and C-propeptides
      of types V and XI procollagen chains to yield monomers that are incorporated into
      and control the diameters of collagen type I and II fibrils, respectively;
      processing of precursors for laminin 5 and collagen type VII, both of which are
      involved in securing epidermis to underlying dermis; and maturation of small
      leucine-rich proteoglycans. The BMP1/TLD-related metalloproteinases are also
      capable of activating the vertebrate transforming growth factor-beta (TGF-beta)
      like "chalones" growth differentiation factor 8 (GDF8, also known as myostatin),
      and GDF11 (also known as BMP11), involved in negative feedback inhibition of
      muscle and neural tissue growth, respectively; by freeing them from noncovalent
      latent complexes with their cleaved prodomains. BMP1/TLD-like proteinases also
      liberate the vertebrate TGF-beta-like morphogens BMP2 and 4 and their
      invertebrate ortholog decapentaplegic, from latent complexes with the vertebrate
      extracellular antagonist chordin and its invertebrate ortholog short gastrulation
      (SOG), respectively. The result is formation of the BMP signaling gradients that
      form the dorsal-ventral axis in embryogenesis. Thus, BMP1/TLD-like proteinases
      appear to be key to regulating and orchestrating formation of the ECM and
      signaling by various TGF-beta-like proteins in morphogenetic and homeostatic
      events.

PMID- 16622849
TI  - Matrix metalloproteinases and cellular motility in development and disease.
AB  - The movement of cells and the accompanied remodeling of the extracellular matrix
      is a critical step in many developmental processes. The matrix metalloproteinases
      (MMPs) are well recognized as mediators of matrix degradation, and their activity
      as regulators of signaling pathways by virtue of the cleavage of nonmatrix
      substrates has been increasingly appreciated. In this review, we focus on the
      role of MMPs in altering processes that influence cellular motility. MMP
      involvement in cellular adhesion, lamellipodia-directed movement, invadopodial
      protrusion, axonal growth cone extension, and chemotaxis are discussed. Although
      not designed to be comprehensive, these examples clearly demonstrate that
      cellular regulation of the MMPs influences cell motility in a variety of ways,
      including regulating cell-cell interactions, cell-matrix interactions, matrix
      degradation, and the release of bioactive signaling molecules. Deregulation of
      these interactions can ultimately result in disorders including inflammatory
      diseases, vascular diseases, bone diseases, neurological disorders, and cancer.

PMID- 16622850
TI  - Parabronchial smooth muscle cells and alveolar myofibroblasts in lung
      development.
AB  - Epithelial-mesenchymal interactions and extracellular matrix remodeling are key
      processes of embryonic lung development. Lung smooth muscle cells, which are
      derived from the mesenchyme, form a sheath around bronchi and blood vessels.
      During lung organogenesis, smooth muscle differentiation coincides with
      epithelial branching morphogenesis and closely follows developing airways
      spatially and temporally. The precise function of parabronchial smooth muscle
      (PBSM) cells in healthy adult lung remains unclear. However, PBSM may regulate
      epithelial branching morphogenesis during lung development by the induction of
      mechanical stress or through regulation of paracrine signaling pathways. Alveolar
      myofibroblasts are interstitial contractile cells that share features and may
      share an origin with smooth muscle cells. Alveolar myofibroblasts are essential
      for secondary septation, a process critical for the development of the gas
      exchange region of the lung. Dysregulation of PBSM or alveolar myofibroblast
      development is thought to underlie the pathogenesis of many lung diseases,
      including bronchopulmonary dysplasia, asthma, and interstitial fibrosis. We
      review the current understanding of the regulation of PBSM and alveolar
      myofibroblast development, and discuss the role of PBSM in lung development. We
      specifically focus on the role of these cells in the context of fibroblast growth
      factor-10, sonic hedgehog, bone morphogenetic protein-4, retinoic acid, and Wnt
      signaling pathways in the regulation of lung branching morphogenesis.

PMID- 16622851
TI  - Quality of life and personality in essential tremor patients.
AB  - The aim of this study was to determine the impact of essential tremor (ET) on
      quality of life and its relation with tremor severity and the personality profile
      of ET patients. One hundred and five patients with definite or probable ET from
      an outpatient population were tested with the Short-Form 36-Item Health Survey
      (SF36) and the Eysenck Personality Questionnaire (EPQ-R). Compared to controls,
      the ET patients scored worse in all eight domains of the SF36. The physical
      component score (PCS) did not differ significantly from the normal population,
      whereas ET patients older than 40 years were significantly more affected with
      regard to the mental domains measured by the mental component score (MCS) with
      their median below the 20th percentile of the German controls. Tremor severity
      correlated with some of the physical domains and the PCS as well as with social
      function of the mental domains. ET patients showed significantly lower scores in
      the psychoticism (P) scale of the EPQ-R, with a median value on the 11th
      percentile of normal German population, indicating a more tender-minded
      personality type. The MCS correlated highly significant with the neuroticism (N)
      scale and extraversion (E) scale of EPQ-R. Multiple regression analysis
      identified age as the only predictive factor for the PCS and the N-scale as the
      only predictive factor for the MCS. Although ET is considered a pure movement
      disorder, the mental components of quality of life are more affected than the
      physical dimensions. A more controlled personality type may in part contribute to
      this.

PMID- 16622852
TI  - Improvement of symptoms following epileptic convulsion in a patient with
      Parkinson's disease.

PMID- 16622853
TI  - Proteases in eye development and disease.
AB  - The eye is one of the classical systems in developmental biology. Furthermore,
      diseases of the eye, many of which have a developmental basis, have devastating
      effects that often result in blindness. Proteases have diverse roles in ocular
      physiology and pathophysiology. Here, a broad overview is provided of the recent
      literature pertaining to the involvement of proteases in various aspects of eye
      development and disease: lens development (focusing on apoptosis and lens fiber
      cell denucleation and organelle loss) and cataract progression, cornea
      development and disease, retina development and degeneration, sclera development
      and myopia, and the trabecular meshwork and glaucoma. Proteases discussed include
      caspases, calpains, matrix metalloproteases (MMPs), a disintegrin and
      metalloproteinases (ADAMs) and ADAM with thrombospondin motifs (ADAMTS), the
      ubiquitin-proteasome pathway (UPP), tissue plasminogen activator (tPA), and
      secretases. It is clear that proteases have diverse and important roles in ocular
      development and disease, and represent, in many cases, useful therapeutic targets
      for treating ocular conditions, which would otherwise lead to visual impairment.

PMID- 16622854
TI  - Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinson's disease
      patients from 18 countries.
AB  - We screened LRRK2 mutations in exon 41 in 904 parkin-negative Parkinson's disease
      (PD) patients (868 probands) from 18 countries across 5 continents. We found
      three heterozygous missense (novel I2012T, G2019S, and I2020T) mutations in LRRK2
      exon 41. We identified 11 (1.3%) among 868 PD probands, including 2 sporadic
      cases and 8 (6.2%) of 130 autosomal dominant PD families. The LRRK2 mutations in
      exon 41 exhibited relatively common and worldwide distribution. Among the three
      mutations in exon 41, it has been reported that Caucasian patients with G2019S
      mutation have a single-founder effect. In the present study, Japanese patients
      with G2019S were unlikely to have a single founder from the Caucasian patients.
      In contrast, I2020T mutation has a single-founder effect in Japanese patients.
      Clinically, patients with LRRK2 mutations had typical idiopathic PD. Notably,
      several patients developed dementia and psychosis, and one with I2020T had low
      cardiac (123)I-metaiodobenzylguanidine (MIBG) heart/mediastinum ratio, although
      the ratio was not low in other patients with I2020T or G2019S. Clinical
      phenotypes including psychosis, dementia, and MIBG ratios are also heterogeneous,
      similar to neuropathology, in PD associated with LRRK2 mutations.

PMID- 16622855
TI  - Long-term cryopreservation of dental pulp stem cells (SBP-DPSCs) and their
      differentiated osteoblasts: a cell source for tissue repair.
AB  - It is not known whether cells derived from stem cells retain their
      differentiation and morpho-functional properties after long-term
      cryopreservation. This information is of importance to evaluate their potential
      for long-term storage with a view to subsequent use in therapy. Here, we describe
      the morpho-functional properties of dental pulp stem cells (SBP-DPSCs), and of
      their differentiated osteoblasts, recovered after long-term cryopreservation.
      After storage for 2 years, we found that stem cells are still capable of
      differentiation, and that their differentiated cytotypes proliferate and produce
      woven bone tissue. In addition, cells still express all their respective surface
      antigens, confirming cellular integrity. In particular, SBP-DPSCs differentiated
      into pre-osteoblasts, showing diffuse positivity for ALP, BAP, RUNX-2, and
      calcein. Recovered osteoblasts expressed bone-specific markers and were easily
      recognizable ultrastructurally, with no alterations observed at this level. In
      addition, after in vivo transplantation, woven bone converted into a 3D lamellar
      bone type. Therefore, dental pulp stem cells and their osteoblast-derived cells
      can be long-term cryopreserved and may prove to be attractive for clinical
      applications.

PMID- 16622856
TI  - Valvular heart disease in Parkinson's disease vs. controls: An echocardiographic
      study.
AB  - Restrictive valvulopathy has been reported in association with dopamine agonist
      therapy in parkinsonian patients. The majority of reports have been related to
      pergolide, but anecdotal cases following treatment with bromocriptine or
      cabergoline have also been presented. It is presently unclear whether the
      potential induction of restrictive cardiac valvulopathy is a class effect of all
      dopamine agonists or if there is a differential risk between ergot and nonergot
      compounds. In this study, the frequency of a valvular regurgitation as assessed
      by routine transthoracic echocardiography was compared between 75 patients with
      Parkinson's disease (PD) treated with pergolide (n = 29), cabergoline (n = 13),
      pramipexole or ropinirole (n = 33), and 49 age-matched nonparkinsonian controls.
      The exposure to pergolide and cabergoline was associated with higher frequencies
      of valvular regurgitation grades 2 and 3 (31% and 47%) compared with age-matched
      controls (13%), while there was no increase of valvular regurgitation grades 2
      and 3 in patients treated with nonergot compounds (10%). Evidence for restrictive
      valvulopathy was found in one patient treated with pergolide and cabergoline
      each. While this study shows similarly increased frequencies of valvular
      regurgitation in patients treated with the ergot agonists pergolide and
      cabergoline in comparison to both normal controls and patients treated with
      nonergot agonists, evidence for restrictive valvulopathy was only found in two
      cases. These results highlight the need for further prospective studies of the
      prevalence and underlying mechanisms of cardiac valvulopathy in PD patients
      treated with different dopamine agonists.

PMID- 16622857
TI  - Protein intake in Parkinsonian patients using the EPIC food frequency
      questionnaire.
AB  - The dietary habits of 45 Italian patients with Parkinson's disease (PD) and their
      spouses were investigated using the EPIC food frequency questionnaire. Average
      daily energy intake was similar, but PD patients consumed significantly more
      vegetable proteins and carbohydrates (both +18%; P = 0.01 and P = 0.001,
      respectively). Daily protein intake, which interferes with levodopa absorption,
      was 50% higher than the recommended daily allowance (1.2 vs. 0.8 g/kg) in both PD
      patients and spouses and was significantly higher in patients with
      moderate/severe symptoms (1.27 +/- 0.29 vs. 1.07 +/- 0.28 g/kg; P < 0.001). In
      patients taking levodopa, there was a correlation between daily levodopa dosage
      and protein intake (P = 0.027). Dietary habits of patients with advanced and/or
      fluctuating PD should always be checked, with particular reference to protein
      intake.

PMID- 16622858
TI  - Analysis of blink rate in patients with blepharospasm.
AB  - The blink rate (BR) during rest, conversation, and reading was assessed in 50
      patients with blepharospasm (BS) and in 150 healthy subjects. BR at rest and
      during conversation was higher in patients with BS. Moreover, 76% of patients had
      BR higher at rest than during conversation, whereas in 74% of controls, BR was
      higher during conversation than at rest. The sensitivity and specificity of two
      parameters (value of BR at rest and pattern rest-BR higher than conversation-BR)
      in discriminating patients and controls were computed. The best fit was obtained
      with a rest-BR above 27 blinks per minute. When the two parameters were combined
      (rest-BR above 27 blinks per minute together with the pattern rest-BR higher than
      conversation-BR), we obtained a 92.3% sensitivity and a 82.0% specificity in
      discriminating between BS patients and controls. These findings indicate that
      specific features of BR can be associated with BS, suggesting that the analysis
      of BR might be helpful for the diagnosis of BS in early stages.

PMID- 16622859
TI  - Frequency and phenotypes of LRRK2 G2019S mutation in Italian patients with
      Parkinson's disease.
AB  - To evaluate the frequency of the LRRK2 G2019S mutation in Italy, we tested 1,072
      probands with Parkinson's disease (PD; 822 sporadic and 250 familial): 20
      patients (1.9%) carried the G2019S mutation, 11 patients (1.3%) were sporadic,
      and 9 (4.3%) had a positive family history. Considering only probands with
      autosomal dominant inheritance, the G2019S frequency raises to 5.2%. All
      presented a typical phenotype with variable onset and shared the common ancestral
      haplotype. Mutation frequency raised from 1.2% in early onset PD to 4.0% in late
      onset PD.

PMID- 16622860
TI  - A possible involvement of beta-endorphin, substance P, and serotonin in rat
      analgesia induced by extremely low frequency magnetic field.
AB  - Most of the research concerning magnetic antinociception was focused on brief
      exposure less than 1 h. The main purpose of the present study was to determine
      the effect of extremely low frequency (ELF) magnetic field (MF) repeated
      exposures on rats in inducing antinociception and to find the effective analgesic
      "time window." Meanwhile this investigation was to examine the role of central
      beta-endorphin, substance P, and 5-HT in magnetic analgesia. We found tail flick
      latencies (TFLs) increased significantly after the rats were exposed to 55.6 Hz,
      8.1 mT magnetic field for 4 days, 6 h each day. The analgesic effects seemed to
      decrease gradually when the rats were exposed daily for another 10 days. Their
      levels of TFLs decreased within 1 day when the rats were removed after a 4-day
      exposure. The concentrations of hypothalamus beta-endorphin, substance P, and
      brainstem serotonin (5-HT) were increased significantly on Day 4. However, no
      differences were found when rats were exposed for another 10 days, and there were
      no significant increases when rats were removed after the fourth day of exposure
      and tested for nociception on Days 5 and 7 with no changes in the biochemical
      markers at 7 days. These results suggest that the ELF magnetic field has
      analgesic effect, but only on Days 3 and 4. The effect may be associated with
      increases in endogenous beta-endorphin, substance P, and 5-HT stimulated by the
      55.6 Hz, 8.1 mT magnetic field.

PMID- 16622861
TI  - Occupational magnetic field exposure and melatonin: interaction with light-at
      night.
AB  - The evidence of magnetic field (MF) effects on melatonin production in humans is
      limited and inconsistent. Part of the inconsistencies might be explained by
      findings suggesting interaction with light in pineal responses to MFs. To test
      this hypothesis, we reanalyzed data from a previously published study on 6
      hydroxy melatonin sulfate (6-OHMS) excretion in women occupationally exposed to
      extremely low-frequency MFs. Based on questionnaire data on exposure to light-at
      night (LAN), and measurement-based MF data, the 60 women were classified to four
      groups: no MF, no LAN; MF, no LAN; no MF, LAN; MF, LAN. The lowest excretion of 6
      OHMS was observed in the group of women who were exposed to both MF and LAN, and
      the differences between the four groups were significant (P < .0001). The result
      is based on low numbers, but supports the hypothesis that daytime occupational
      exposure to MF enhances the effects of nighttime light exposure on melatonin
      production.

PMID- 16622862
TI  - Effect of cyclophosphamide and 61.22 GHz millimeter waves on T-cell, B-cell, and
      macrophage functions.
AB  - The present study was undertaken to investigate whether millimeter waves (MMWs)
      at 61.22 GHz can modulate the effect of cyclophosphamide (CPA), an anti-cancer
      drug, on the immune functions of mice. During the exposure each mouse's nose was
      placed in front of the center of the antenna aperture (1.5 x 1.5 cm) of MMW
      generator. The device produced 61.22 +/- 0.2 GHz wave radiation. Spatial peak
      Specific Absorption Rate (SAR) at the skin surface and spatial peak incident
      power density were measured as 885 +/- 100 W/kg and 31 +/- 5 mW/cm(2),
      respectively. Duration of the exposure was 30 min each day for 3 consecutive
      days. The maximum temperature elevation at the tip of the nose, measured at the
      end of 30 min, was 1 degrees C. CPA injection (100 mg/kg) was given
      intraperitoneally on the second day of exposure to MMWs. The animals were
      sacrificed 2, 5, and 7 days after CPA administration. MMW exposure caused
      upregulation in tumor necrosis factor-alpha (TNF-alpha) production in peritoneal
      macrophages suppressed by CPA administration. MMWs also caused a significant
      increase in interferon-gamma (IFN-gamma) production by splenocytes and enhanced
      proliferative activity of T-cells. Conversely, no changes were observed in
      interleukin-10 (IL-10) level and B-cell proliferation. These results suggest that
      MMWs accelerate the recovery process selectively through a T-cell-mediated immune
      response.

PMID- 16622863
TI  - Effect of electromagnetic nanopulses on C. elegans fertility.
AB  - Electromagnetic nanopulse exposure results in decreased fertility of C. elegans,
      a well studied, multicellar organism. Experiments indicate that this effect is
      unlikely to be due to heating. Instead, nanopulses interfere with fertilization
      or development by an as yet undetermined mechanism. Study of nanopulse exposure
      of C. elegans could help to understand more generally how living organisms
      interact with electromagnetic fields.

PMID- 16622865
TI  - Interaction of radio frequency electromagnetic fields and passive metallic
      implants--a brief review.
AB  - During the last decade, use of radio frequency (RF) applications like mobile
      phones and other wireless devices, has increased remarkably. This has triggered
      numerous studies related to possible health risks due to the exposure of RF
      electromagnetic (EM) fields. One safety aspect is the coupling of EM fields with
      active and passive implants in the human body. While interactions with active
      implants have been quite extensively researched, only a few studies have focused
      on passive implants. The present article reviews interaction mechanisms and
      studies of passive metallic, that is, conductive, implants in common external RF
      EM fields. It is found that implants have been mostly studied numerically, and
      experimental studies are rare. Furthermore, the studies cover mostly far-field
      conditions and only a few have studied implants in near fields. A summary of
      results indicates that a conductive object in tissues may cause notable local
      enhancement of the EM field and thus enhanced power absorption. The degree of
      enhancement depends, for example, on the orientation, the dimensions, the shape,
      and the location of the implant. However, in most of the cases, the field
      enhancement has not been strong enough to cause remarkable excess heating (more
      than 1 degrees C) of tissues.

PMID- 16622864
TI  - Effects of a 2450 MHz high-frequency electromagnetic field with a wide range of
      SARs on the induction of heat-shock proteins in A172 cells.
AB  - In this study, we investigated whether exposure to 2450 MHz high-frequency
      electromagnetic fields (HFEMFs) could act as an environmental insult to evoke a
      stress response in A172 cells, using HSP70 and HSP27 as stress markers. The cells
      were exposed to a 2450 MHz HFEMF with a wide range of specific absorption rates
      (SARs: 5-200 W/kg) or sham conditions. Because exposure to 2450 MHz HFEMF at 50
      200 W/kg SAR causes temperature increases in culture medium, appropriate heat
      control groups (38-44 degrees C) were also included. The expression of HSP 70 and
      HSP 27, as well as the level of phosphorylated HSP 27 ((78)Ser) (p-HSP27), was
      determined by Western blotting. Our results showed that the expression of HSP 70
      increased in a time and dose-dependent manner at >50 W/kg SAR for 1-3 h. A
      similar effect was also observed in corresponding heat controls. There was no
      significant change in HSP 27 expression caused by HFEMF at 5-200 W/kg or by
      comparable heating for 1-3 h. However, HSP 27 phosphorylation increased
      transiently at 100 and 200 W/kg to a greater extent than at 40-44 degrees C.
      Phosphorylation of HSP 27 reached a maximum after 1 h exposure at 100 W/kg HFEMF.
      Our results suggest that exposure to a 2450 MHz HFEMF has little or no apparent
      effect on HSP70 and HSP27 expression, but it may induce a transient increase in
      HSP27 Phosphorylation in A172 cells at very high SAR (>100 W/kg).

PMID- 16622866
TI  - Occupational 50 Hz magnetic field exposure measurements among female sewing
      machine operators in Hungary.
AB  - Occupational magnetic field (MF) exposure is less thoroughly characterized in
      occupations typically held by women. Our objective was to characterize
      occupational 50 Hz MF personal exposure (PE) among female sewing machine
      operators. We measured the full shift PE of 51 seamstresses, who worked in two
      shifts (6-14 and 14-22 h) according to their normal work routine. Measurements
      were conducted using EMDEX PAL meters at chest level. The average duration of the
      measurement periods was 449 min (range 420-470). The average arithmetic mean
      exposure for all women was 0.76 microT (range 0.06-4.27). The average of maximum
      values was 4.30 microT (range 0.55-14.80). Women working with older sewing
      machines experienced higher exposure than women working on newer sewing machines.
      For women (n = 10) who operated sewing machines produced in 1990 or earlier, the
      average arithmetic mean exposure was 2.09 microT, and for women (n = 41) who
      operated sewing machines produced after 1990, the average arithmetic mean was
      0.43 microT. We conclude that women working as sewing machine operators
      experience higher than average occupational MF exposure compared to other working
      women. Most important determinant of the women's personal MF exposure was the age
      of the sewing machine the women operated.

PMID- 16622868
TI  - HIV variants and hepatitis B surface antigen mutants.

PMID- 16622869
TI  - HIV variants and hepatitis B surface antigen mutants: diagnostic challenges for
      immunoassays.

PMID- 16622870
TI  - Global epidemiology of HIV.
AB  - HIV is among the most generically variable of human pathogens. A comprehensive
      and detailed description of HIV strains in the pandemic is an important
      foundation for diagnosis, treatment, and prevention. The current sequence
      database for HIV includes almost 800 complete genome sequences, documenting HIV-1
      groups M, O, and N, and HIV-2. Among HIV-1 group M strains, responsible for the
      vast majority of HIV infections worldwide, 743 sequences represent 9 genetic
      subtypes, 16 circulating recombinant forms (CRF) that are spreading in
      populations, and a variety of unique recombinant forms (URF), identified so far
      only from a single individual. The global distribution of HIV is complex and
      dynamic with regional epidemics harboring only a subset of the global diversity.
      HIV strains differ enormously in terms of global prevalence. Six strains account
      for the majority of HIV infections: HIV-1 subtypes A, B, C, D, and two of the
      CRF, CRF01-AE and CRF02_AG, respectively. Many of the known subtypes and
      recombinant forms are currently rare in the epidemic, but could spread more
      widely if favorable conditions arise. HIV-2 is largely restricted to West Africa
      at relatively low prevalence there. Groups O and N of HIV-1 are very rare in the
      pandemic. The goal of universal coverage of HIV-1 strains by diagnostic tests can
      be met by minimizing false negative test rates for the six globally prevalent HIV
      1 group M strains and HIV-2, and by evaluating systematically coverage of rare
      subtypes and recombinant forms.

PMID- 16622872
TI  - The changing epidemiology of HIV/AIDS at a Minnesota hospital: impact of
      demographic change and viral diversity.
AB  - The past decade has seen a dramatic influx of African-born immigrants and
      refugees into Minnesota. The impact of this on Hennepin County Medical Center
      (HCMC), a public teaching hospital located in Minneapolis, has been considerable,
      especially in the management of HIV-infected persons given that approximately 30%
      of newly diagnosed individuals seen at HCMC in the past 3 years acquired the
      virus in Africa. An ongoing and permanent alteration in the demographics of
      HIV/AIDS in this part of the American midwest is clearly occurring, therefore,
      accompanied by considerable diversification of the viral makeup of the epidemic.
      The following article describes currently available data on the viral
      characteristics of the African-born HIV-infected population of Minnesota and
      highlights the potential impact of this expanding viral diversity on the ability
      of the clinical laboratory at HCMC to provide the virologic information necessary
      to manage effectively patients infected with the HIV virus.

PMID- 16622871
TI  - Human immunodeficiency virus serotyping on dried serum spots as a screening tool
      for the surveillance of the AIDS epidemic.
AB  - Many studies have demonstrated the utility of the dried blood spot (DBS) or dried
      plasma/serum spot (DSS) method for serological and molecular diagnosis of HIV
      infection. Here, we report on the description of a serotyping assay performed on
      DSS, and its application to a national surveillance program of HIV variants. We
      combined serotyping assays that we developed previously to discriminate between
      HIV-1 and HIV-2, between HIV-1 group O and HIV-1 group M, and between B and non-B
      subtypes of HIV-1 group M. The assays are based on antibody binding to either the
      immunodominant epitope of gp41 or the V3 domain of gp120 of these various types,
      groups and subtypes. Therefore, a unique enzyme-linked immunosorbent assay
      (ELISA) format applied to serum eluted from DSS allowed the simultaneous
      discrimination between infections caused by HIV-1 B, HIV-1 non-B, HIV-1 group O,
      and HIV-2. Together, this serotyping assay and an immunoassay for recent
      infection were used for a virological surveillance linked to the anonymous
      mandatory notification of HIV infection in France. The preliminary results of
      this virological surveillance allowed us to obtain estimates of the prevalence of
      the rare variants HIV-2 and HIV-1 group O. It also allowed identification of the
      two first cases of M/O dual infections reported outside the endemic group O
      region of the western part of equatorial Africa, and showed that non-B subtypes
      circulate widely in France, almost 50% of new HIV diagnoses in 2003 being due to
      these variants.

PMID- 16622873
TI  - Evaluation of FDA licensed HIV assays using plasma from Cameroonian blood donors.
AB  - Several diagnostic assays for the detection of HIV infection have been approved
      and licensed by the FDA for blood donor screening. However, the performance of
      these assays is unknown when testing genetically divergent blood specimens. To
      evaluate the performance of these assays with diverse HIV strains, we chose to
      study specimens collected from blood donors in Cameroon where genetic diversity
      and recombinant variants are prevalent. In this study, we tested 240 human plasma
      specimens collected from two blood centers in Cameroon. These samples were
      screened initially in Cameroon for antibody to HIV using a rapid assay. We also
      performed sequencing to determine subtype. Our evaluation has demonstrated that
      HIV infection in most HIV plasma samples could be detected by most of the US FDA
      licensed diagnostic assays. With the exception of a few specimens, HIV-1 p24
      antigen was not detected in any of the samples. In addition, some nucleic acid
      tests (NAT) assays were not able to detect a few serologic reactive samples and
      all new variants including some CRF02_AG variants.

PMID- 16622874
TI  - HIV global surveillance: foundation for retroviral discovery and assay
      development.
AB  - The high level of HIV genetic diversity has important implications for screening,
      diagnostic testing and patient monitoring. Continued diversification and global
      redistribution of HIV groups, subtypes and recombinants make it imperative that
      serological and molecular assays be designed and evaluated to ensure reliable
      performance on all HIV infections. Recognizing the importance of this issue, we
      initiated a comprehensive program to monitor global diversification of HIV,
      search for newly emerging variants, assemble large-volume panels of genetically
      and geographically diverse strains, and develop strategies to determine the
      impact of HIV diversity on assays used for detecting and monitoring HIV
      infection. Efforts to identify and characterize rare and emerging HIV strains
      have lead to the identification of HIV-1 group O, group N, and dual infections of
      groups M and O. A panel of plasma specimens was established that includes
      specimens collected from 12 countries in Africa, Asia, Europe, and South America;
      the panel comprises infections due to HIV-1 group M subtypes A, B, C, D, F, and
      G, as well as CRF01, CRF02, and unique recombinant forms, group N, and group O.
      Serological and molecular characterization of this unique panel has provided
      vital sequence data to support assay development and an invaluable source of well
      defined specimens to evaluate and compare assay performance. The ability to
      address the challenge posed by ongoing evolution of HIV and the emergence of new
      variants requires continued surveillance of global HIV strain diversity, a sound
      scientific foundation for assay development, and suitable panels to evaluate and
      validate assay performance.

PMID- 16622875
TI  - Surveillance of the genetic variation in incident HIV, HCV, and HBV infections in
      blood and plasma donors: implications for blood safety, diagnostics, treatment,
      and molecular epidemiology.
AB  - Surveillance for molecular variants in blood donors is vital to assuring that
      blood screening and supplemental assays are sensitive to circulating strains of
      blood-borne viruses. Blood screening and diagnostic assays licensed in the United
      States are largely based on prototype viral strains. Documentation of divergent
      viral strains in the donor pool can lead to accelerated development and licensure
      of robust serologic and nucleic acid amplification (NAT) assays for donor
      screening and diagnostic applications. In addition, surveillance for viral
      variants among donors has implications for assessing the prevalence of drug and
      vaccine escape mutants and for detecting and monitoring rare variants that may be
      newly introduced or increasing in the United States donor population. Combined
      NAT and serologic screening, supplemented by novel serologic testing strategies,
      can be used to identify donors with incident infections, which are of particular
      interest with respect to blood safety and public health implications. A
      systematic program is proposed for the genetic characterization of viral genomes
      in donors with incident HIV, HCV, or HBV infections.

PMID- 16622876
TI  - Hepatitis B virus genetic diversity.
AB  - Hepatitis B virus (HBV) is a human DNA virus, which replicates through an RNA
      intermediate because of the reverse-transcriptase (RT) activity of its DNA
      polymerase. As a result, the mutation rate for HBV is higher than the rate
      observed for most DNA viruses. HBVs are classified into genotypes based on
      genomic sequencing, and antigenic subtypes based on the antigenic properties of
      its major surface glycoprotein, the HBV surface antigen (HBsAg). Subgenotypes
      have been identified within most of the HBV genotypes. The HBV groups defined by
      the different genotype-HBsAg subtype associations found over the world display
      characteristic geographical distributions, reflecting the movements of human
      populations and other epidemiologically significant events. Such HBV groups
      constitute genetically stable viral populations sharing a common evolutionary
      history, but additional stable changes, originating from mutation and mutant
      selection, are observed within all of them. These viral sub-populations are known
      as the HBV variants, and some of which have medical and public health relevance.
      Pre-core (pre-C) defective variants have been shown to make HBV infection much
      less susceptible to interferon treatment, and treatment failures with other
      antiviral drugs have been associated with selection of resistant variants that
      display specific mutations in the genome region encoding the viral RT activity.
      Since the RT region of the genome overlaps the sequence encoding the HBsAg
      molecule, selection of drug resistant variants involves, in some cases, the
      indirect selection of HBsAg variants. Viral variants displaying changes in HBsAg
      seem to be very common among chronic HBV carriers; and some of these variants may
      emerge under the pressure of the neutralizing antibody response, leading to
      vaccine resistance and resistance to immunotherapy. Mutations conferring
      resistance to immunotherapy are noted often among liver transplant recipients and
      among babies born to HBV-carrier mothers. In addition, some of these HBsAg
      variants have been associated with lack of detection by HBsAg tests used for the
      diagnosis of HBV infection, for the identification of chronic carriers, for
      screening of blood donations for transfusion, and in the manufacture of
      therapeutic blood products.

PMID- 16622877
TI  - Detection of HBsAg mutants.
AB  - HBsAg screening is carried out routinely to detect hepatitis B virus (HBV)
      infection. The immunoassays used employ capture antibodies often having
      specificity for epitopes present on the antigenic (a) determinant of the HBsAg.
      Loss of detection may occur due to mutations within and/or outside of the a
      determinant that affect conformational epitope recognition or HBsAg secretion or
      expression. Most of the mutations associated with immune escape occur within the
      second loop of the a determinant. In order to detect these HBsAg mutants,
      antibodies to subdominant regions within the a determinant or outside of the
      HBsAg may be required, and this has been the focus of many recent studies. Any
      changes to immunoassay formulations should also address the possible effect of
      HBV genotypic polymorphisms on assay specificity and sensitivity. HBsAg mutants
      may also be identified through nucleic acid detection of HBV in serum. Various
      molecular analysis methods have been developed to provide specific and sensitive
      detection of HBsAg mutants, including sequencing, limiting dilution cloning PCR
      (LDC-PCR), gap ligase chain reaction (gLCR), and real time PCR. Sequencing the
      HBsAg coding region provides specific information on the nucleotide sequence;
      however, it is relatively insensitive for the detection of minority quasispecies.
      Other nucleic acid methods offer greater sensitivity for the detection of point
      mutations. To improve immunoassays, further research will be required to increase
      detection sensitivity and specificity. Ultimately, a better understanding of the
      structure of antibody-bound HBsAg will help identify the immunological targets
      required for the accurate detection of HBsAg in blood.

PMID- 16622878
TI  - Hepatitis B virus mutations associated with antiviral therapy.
AB  - The hepatitis B virus (HBV) replicates via an error prone viral reverse
      transcriptase resulting in a large pool of quasispecies with mutations spread
      throughout the genome. During antiviral drug selection pressure (e.g.,
      lamivudine, adefovir, or entecavir) HBV mutants are selected from the pre
      existing pool of quasispecies and over time become the dominant species. Not all
      mutations result in replication competent virus as HBV has the added complexity
      of overlapping reading frames. The HBV polymerase (Pol) gene overlaps the
      hepatitis B surface antigen (HBsAg) in a frame-shifted manner with the result
      that drug-resistant mutations in the HBV Pol can directly impact on the nature of
      HBsAg and its function. HBV genomic databases have been established to monitor
      antiviral selected mutations and are useful in determining conserved residues,
      genotypic differences, polymorphisms, and the mutation profiles selected under
      different antiviral selection pressures. These HBV databases may aid in the
      development of new diagnostic reagents as well as the monitoring of polymerase
      and envelope mutations selected under different antiviral pressures. Antiviral
      drug resistant mutants emerge as a function of at least six factors: the viral
      mutation frequency, the intrinsic mutability of the antiviral target site, the
      selective pressure exerted by the drug, the magnitude and rate of virus
      replication, the overall replication fitness of the mutant, and the availability
      of replication space. Only a limited number of HBsAg mutations selected during
      antiviral treatment have been characterized and the diagnostic and public health
      implications of these mutations need further investigation. Clearly, improved
      treatment strategies are required urgently to prevent the continued selection of
      HBV drug-resistant mutants.

PMID- 16622879
TI  - Surveillance for hepatitis B surface antigen mutants.
AB  - Hepatitis B viral (HBV) mutants can emerge in patients as a result of selection
      pressure from treatment options. Some mutations that occur in the immunodominant
      "a" determinant of hepatitis B surface antigen (HBsAg) can present as false
      negative results in HBsAg immunoassays. The mutation position in HBsAg and the
      type of mutation impacts immunoassay performance. HBsAg mutants will continue to
      emerge in response to selection pressure, therefore an appropriate HBV
      immunoassay-testing algorithm needs to be established to ensure their detection.
      Mutant surveillance programs can also contribute to our understanding of the
      changing epidemiology of HBV infection.

PMID- 16622880
TI  - Diagnostic impact of the genetic variability of the hepatitis B virus surface
      antigen gene.
AB  - The genetic variability of hepatitis B virus (HBV) represents a challenge for the
      sensitivity of immunologic and molecular based assays. Genotyping studies show
      that the genetic diversity of HBV is very high even in industrialized countries.
      The analytical sensitivity of HBsAg and anti-HBs assays may be dependent on HBV
      genotype or subtype and could possibly lead to false negative results in samples
      with low-level HBsAg. It is possible that the recognition of genotypes E and F
      may be impaired. Immunoassays based on polyclonal capture antibody show the
      highest sensitivity for the recognition of recombinant mutants or serum samples
      harboring mutant forms of HBsAg. However, they do not guarantee full sensitivity,
      especially for the detection of the G145R mutation and amino acid insertions or
      substitutions in positions 120-123. Detection of HBsAg needs to be improved by
      the introduction of new HBsAg assays able to recognize so far described S gene
      mutants and with a lower detection threshold than current immunoassays in order
      to detect smallest amounts of HBsAg in low level carriers. There is also a need
      for more complete epidemiological data on the prevalence of HBsAg mutants
      especially for G145R and assays for the (differential) screening of mutants need
      to be developed and evaluated.

PMID- 16622881
TI  - Evaluation of 17 CE-marked HBsAg assays with respect to clinical sensitivity,
      analytical sensitivity, and hepatitis B virus mutant detection.
AB  - Seventeen HBsAg assays, in use in the European market (CE-marked), were assessed
      for their diagnostic sensitivity using 38 commercially available seroconversion
      panels, and for their analytical sensitivity with the HBsAg ad and ay standards
      of the Paul-Ehrlich-Institut (PEI). In addition, the ability to detect HBsAg
      mutants was investigated by means of 21 recombinant HBsAg mutant samples and 5
      natural mutants. Analysis of seroconversion data revealed that there were marked
      differences in the sensitivity among the CE-marked HBsAg assays. Differences in
      the window period between the most and the least sensitive assays were up to 2
      weeks. Analytical sensitivities of the investigated assays ranged from 0.009 to
      0.05 PEI-U/ml for HBsAg ad standard (relating to approximately 0.018 to 0.100
      IU/ml of the 2nd WHO HBsAg standard) and 0.012 to 0.11 PEI-U/ml for the ay
      standard. Clinical and analytical sensitivities were basically correlated. The
      capacity to detect mutant HBsAg forms was influenced by the assay format and the
      properties of the monoclonal antibodies used for coating of the solid phase or in
      the conjugate. While some assays detected all mutants others exhibited weaknesses
      especially in recognising HBsAg mutations affecting loop 2 of the HBsAg a
      determinant. The results obtained with the recombinant mutants were largely
      confirmed by the investigation of clinical samples. The study gives a broad
      overview of the current state of the art of about 70% of the HBsAg assays
      currently available in Europe. The overall sensitivity has not been improved
      further since 1995 when the most sensitive assay was introduced into the market.
      In addition, detection of HBsAg mutants seems problematic with several assays. It
      is concluded that there is potential to improve clinical sensitivity and mutant
      recognition of HBsAg assays.

PMID- 16622882
TI  - Infections by hepatitis B surface antigen gene mutants in Europe and North
      America.
AB  - Hepatitis B virus (HBV) mutants have usually been studied in patients in Asia
      because of the wider use of HBV immunization there and the resultant emergence of
      viral mutants. Nevertheless, HBV surface antigen (S) gene mutants also are found
      in Europe and North America. In Europe and North America, HBV with mutations in
      the portion of the S gene coding the "a" determinant of the hepatitis B surface
      antigen (HBsAg) have been documented in small numbers of infants born to HBV
      infected mothers following post-natal HBV vaccine and hepatitis B immune globulin
      (HBIG) prophylaxis and in many liver transplant recipients who develop HBV re
      infection despite HBIG prophylaxis. In some cases, these mutations have included
      a glycine to arginine substitution at position 145 (G145R), which results in a
      conformational change and different reactivity to monoclonal antibody reagents
      than that of the wild-type virus. Mutations in the a determinant (but not G145R)
      also have been reported in European patients with chronic HBV infection who have
      not received HBV vaccine or HBIG. However, it appears that such mutations are
      only responsible for a small proportion of "occult" or "silent" HBV infections,
      which are characterized by the presence of HBV DNA in serum in the absence of
      detectable HBsAg. However, some of these mutant forms of HBV in cases of occult
      HBV may theoretically escape detection and could present a risk to blood safety.

PMID- 16622883
TI  - Scalable production of adeno-associated virus type 2 vectors via suspension
      transfection.
AB  - Vectors derived from adeno-associated virus type 2 (AAV2) are promising gene
      delivery vehicles, but it is still challenging to get the large number of
      recombinant adeno-associated virus (rAAV) particles required for large animal and
      clinical studies. Current transfection technology requires adherent cultures of
      HEK 293 cells that can only be expanded by preparing multiple culture plates. A
      single large-scale suspension culture could replace these multiple culture
      preparations, but there is currently no effective co-transfection scheme for
      generating rAAV from cells in suspension culture. Here, we weaned HEK 293 cells
      to suspension culture using hydrogel-coated six-well culture plates and
      established an efficient transfection strategy suitable for these cells. Then the
      cultures were gradually scaled up. We used linear polyethylenimine (PEI) to
      mediate transfection and obtained high transfection efficiencies ranging from 54%
      to 99%, thereby allowing efficient generation of rAAV vectors. Up to 10(13) rAAV
      particles and, more importantly, up to 10(11) infectious particles were generated
      from a 2-L bioreactor culture. The suspension-transfection strategy of this study
      facilitates the homogeneous preparation of rAAV at a large scale, and holds
      further potential as the basis for establishing a manufacturing process in a
      larger bioreactor.

PMID- 16622884
TI  - Kinetic study of thermal Z to E isomerization reactions of azobenzene and 4
      dimethylamino-4'-nitroazobenzene in ionic liquids [1-R-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide with R = butyl, pentyl, and hexyl].
AB  - Thermal Z to E isomerization reactions of azobenzene and 4-dimethylamino-4'
      nitroazobenzene were examined in three ionic liquids of general formula 1-R-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide (R = butyl, pentyl, and
      hexyl). The first-order rate constants and activation energies for the reactions
      of azobenzene measured in these ionic liquids were consistent with those measured
      in ordinary organic solvents, which indicated that the slow isomerization through
      the inversion mechanism with a nonpolar transition state was little influenced by
      the solvent properties, such as the viscosity and dielectric constant, of ionic
      liquids. On the other hand, the rate constants and the corresponding frequency
      factors of the Arrhenius plot were significantly reduced for the isomerization of
      4-dimethylamino-4'-nitroazobenzene in ionic liquids compared with those for the
      isomerization in ordinary organic molecular solvents with similar dielectric
      properties. Although these ionic liquids are viscous, the apparent viscosity
      dependence of the rate constant could not be explained either by the Kramers
      Grote-Hynes model or by the Agmon-Hopfield model for solution reactions. It is
      proposed that the positive and the negative charge centers of a highly polar
      rotational transition state are stabilized by the surrounding anions and cations,
      respectively, and that the ions must be rearranged so as to form highly ordered
      solvation shells around the charge centers of the reactant in the transition
      state. This requirement for the orderly solvation in the transition state results
      in unusually small frequency factors of 10(4)-10(7) s(-1).

PMID- 16622885
TI  - Aerobic oxidation of alcohols in carbon dioxide with silica-supported ionic
      liquids doped with perruthenate.
AB  - The replacement of toxic Cr(VI) for O2 and of chlorinated solvents for
      supercritical carbon dioxide (or ionic liquids) in the oxidation of alcohols
      remains hindered by the low selectivity and activity of the current heterogeneous
      catalysts. Using an integrated approach that combines sol-gel entrapped
      perruthenate as aerobic catalyst, an encapsulated ionic liquid as solubility
      promoter, and scCO2 as the reaction solvent, we have developed a system capable
      of rapidly converting different alcohols into carbonyl compounds with complete
      selectivity, including substrates which are otherwise difficult to oxidise. The
      methodology is generally applicable and may easily be extended to other waste
      free, catalytic syntheses of fine chemicals.

PMID- 16622886
TI  - Water gelation of an amino acid-based amphiphile.
AB  - The water immobilization by a simple amino acid-containing cationic surfactant
      was investigated. A variety of techniques, such as (1)H NMR spectroscopy,
      circular dichroism (CD), steady-state fluorescence spectroscopy, and field
      emission scanning electron microscopy (FESEM) were applied to determine the
      formation and architecture of the hydrogel. The new gelator with a minimum
      gelation concentration (MGC) of 0.3 % w/v shows prolonged stability and a low
      melting temperature (39 degrees C). (1)H NMR experiments revealed that
      intermolecular hydrogen bonding between the amide groups and pi-pi stacking of
      the indole rings are the two regulating parameters for gelation. Furthermore,
      fluorescence studies with 8-anilino-1-naphthalenesulfonic acid (ANS) as the probe
      indicate the participation of hydrophobicity during gelation. The luminescence
      study using both ANS and pyrene, along with FESEM results, indicate a critical
      concentration, well below the MGC, at which fibres begin to form. These cross
      link further to give thicker fibers, leading to the formation of a hydrogel (0.3
      % w/v). This new hydrogelator expresses high supramolecular chirality, as
      evidenced by the CD spectra. In addition, the gelator molecule was found to be
      nontoxic up to a concentration of 4 mM (0.2 % w/v). The high supramolecular
      chirality, prolonged stability, low melting point, and biocompatibility of the
      molecule make it a focus of chemical and biological interest.

PMID- 16622887
TI  - A general approach for the identification of site-specific RNA binders by 19F NMR
      spectroscopy: proof of concept.

PMID- 16622888
TI  - The Zintl Ion [Pb10]2-: a rare example of a homoatomic closo cluster.

PMID- 16622889
TI  - Sigma-donor and pi-acceptor stacking interactions in a trans-2-linked C60
      cobalt(II) tetraphenylporphyrin diad.

PMID- 16622890
TI  - Space filling versus symmetry: two consecutive crystal-to-crystal phase
      transitions in a 2D network.

PMID- 16622891
TI  - Proteomic analysis of protein profiles during early development of the zebrafish,
      Danio rerio.
AB  - In the present study, profiles of protein expression were examined during early
      development of zebrafish, an increasingly popular experimental model in
      vertebrate development and human diseases. By 2-DE, an initial increase in
      protein spots from 6 h post-fertilization (hpf) to 8-10 hpf was observed. There
      was no dramatic change in protein profiles up to 18 hpf, but significant changes
      occurred in subsequent stages. Interestingly, 49% of the proteins detected at 6
      hpf remained detectable by 1 week of age. To map the protein expression patterns
      in 2-D gels, MALDI-TOF/TOF MS was employed to identify selected protein spots
      from early embryos. 108 protein spots were found to match known proteins and they
      were derived from 55 distinct genes. Interestingly, 11 (20%) of them produced
      multiple protein isoforms or distinct cleavage products. Although deyolked
      embryos were used in the analysis, a large number of vitellogenin derivatives
      remained prominently present in the embryos. Other than these, most of the
      identified proteins are cytosolic, cytoskeletal and nuclear proteins, which are
      involved in diversified functions such as metabolism, cytoskeleton, translation,
      protein degradation, etc. Some of the proteins with interesting temporal
      expression profiles during development are further discussed.

PMID- 16622892
TI  - A (Tetrasilacyclobutadiene)tricarbonyliron complex [{eta4
      (tBu2MeSi)4Si4}Fe(CO)3]: the silicon cousin of pettit's
      (cyclobutadiene)tricarbonyliron complex [(eta4-H4C4)Fe(CO)3].

PMID- 16622893
TI  - Reactive polymer coatings that "Click".

PMID- 16622894
TI  - Nickel(II) thiolate complexes with a flexible cyclo-{Ni10S20} framework.

PMID- 16622895
TI  - Gold-organic-inorganic high-surface-area materials as precursors of highly active
      catalysts.

PMID- 16622896
TI  - Re: Oda et al. Frequent alteration of p16INK4a/p14ARF and p53 pathways in the
      round cell component of myxoid/round cell liposarcoma: p53 gene alterations and
      reduced p14ARF expression both correlate with poor prognosis. J Pathol
      2005;207:410-421.

PMID- 16622898
TI  - Expression and regulation of human beta-defensin-2 in osteoarthritic cartilage.
AB  - Defensins are antibiotic peptides that are involved in host defence at epithelial
      and mesenchymal surfaces. Previous studies have shown the induction of human beta
      defensin-3 (HBD-3) in osteoarthritic joints, suggesting that these molecules have
      functions in addition to their ability to kill microbes. The aim of this study
      was to investigate the production of a further human beta-defensin, named HBD-2,
      in osteoarthritis (OA) and to determine its regulation by inflammatory cytokines.
      Healthy and osteoarthritic cartilage was assessed for HBD-2 expression by RT-PCR,
      immunohistochemistry, and ELISA. C28/I2 chondrocytes, primary chondrocytes, and
      cartilage explants were cultured for in vitro studies. After 24 h of stimulation
      with tumour necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or IL-6, real
      time RT-PCR and ELISA experiments were performed to evaluate the effect of these
      cytokines on the production of HBD-2. In contrast to healthy cartilage, HBD-2
      expression was identified in most of the OA samples examined (eight of ten).
      Cytokines that are potentially involved in the pathogenesis of OA, namely TNF
      alpha, IL-1, and IL-6, were transcriptional inducers of HBD-2 in cultured
      chondrocytes and cartilage explants in vitro, as measured by real-time RT-PCR and
      ELISA. These results illustrate the induction of HBD-2 in osteoarthritic
      cartilage and suggest that it is a further factor in the pathogenesis of OA.
      However, further studies are required to elucidate the role played by HBD-2 in
      osteoarthritic cartilage.

PMID- 16622899
TI  - EXT-related pathways are not involved in the pathogenesis of dysplasia
      epiphysealis hemimelica and metachondromatosis.
AB  - Dysplasia epiphysealis hemimelica (DEH) and metachondromatosis (MC) are
      considered in the differential diagnosis of solitary and hereditary
      osteochondromas. Both are rare disorders with DEH demonstrating cartilaginous
      overgrowth of an epiphysis and MC exhibiting synchronous enchondromas and
      osteochondromas. Ten cases of DEH and two of MC were compared with
      osteochondromas at the histological and molecular level. Histologically, clumping
      of chondrocytes within a fibrillary chondroid matrix is characteristic of DEH,
      while osteochondromas and MC display the characteristic growth plate
      architecture. Using cDNA microarray analysis we demonstrate that DEH and MC
      cluster separately from osteochondromas and growth plates. The EXT genes,
      involved in the hereditary multiple osteochondromas syndrome, and downregulated
      in osteochondroma, were normally expressed in DEH and MC as shown by quantitative
      reverse transcriptase-polymerase chain reaction (qPCR). EXT is involved in
      heparan sulphate biosynthesis, important for Indian Hedgehog/ParaThyroid Hormone
      Like Hormone (IHH/PTHLH) growth plate signalling pathways. IHH/PTHLH signalling
      molecules were expressed in DEH and MC as shown by both qPCR and
      immunohistochemistry, suggesting that this pathway is active. This is in contrast
      to osteochondroma, in which PTHLH signalling is downregulated. Thus, lesions of
      DEH and MC are separate entities from osteochondroma as confirmed by their
      different cDNA and protein expression profiles. Downstream targets of EXT, which
      are downregulated in osteochondroma, are expressed in DEH and MC, suggesting that
      EXT signalling is not disturbed.

PMID- 16622900
TI  - Fluorodeoxyglucose positron emission tomography with sentinel lymph node biopsy
      for evaluation of axillary involvement in breast cancer.
AB  - BACKGROUND: This study analysed the value of [(18)F]fluorodeoxyglucose positron
      emission tomography (FDG-PET) in detecting axillary lymph node involvement in
      women with breast cancer. METHODS: In the first 150 women in this prospective
      study, axillary lymph node dissection (ALND) was performed regardless of the PET
      results. In a second group (125 women) FDG-PET was complemented with sentinel
      lymph node biopsy (SLNB) only in those who did not have pathological axillary
      uptake. RESULTS: The sensitivity and specificity of FDG-PET in detecting axillary
      involvement was 84.5 and 98.5 per cent respectively in the whole series of 275
      patients, with two false-positive and 22 false-negative results. False-negative
      results were associated with some intrinsic tumour characteristics. In 21 women,
      PET revealed pathological uptake, suggesting involvement of the internal mammary
      lymph node chain. Whole-body PET identified a second synchronous tumour in five
      asymptomatic patients and haematogenous metastases in two patients. CONCLUSION:
      The high positive predictive value of PET (98.4 per cent) suggests that FDG
      uptake in the axilla could be an indication for full ALND without previous SLNB.

PMID- 16622901
TI  - Population-based study of prognostic factors in stage II colonic cancer.
AB  - BACKGROUND: Adjuvant chemotherapy in stage II colorectal cancer may be considered
      for patients whose tumours have poor prognostic features. The aim of this study
      was to evaluate the prognostic significance of commonly reported clinical and
      pathological features of stage II colonic cancer. METHODS: A population-based
      observational study of all patients with stage II colonic cancer diagnosed in the
      state of Western Australia from 1993 to 2003 was performed. A total of 1306
      patients treated by surgery alone were identified, with a median follow-up of 59
      (range 0-145) months. RESULTS: Multivariable analysis revealed that the only
      independent prognostic factors for disease-specific survival were stage T4
      (hazard ratio (HR) 1.75 (95 per cent confidence interval (c.i.) 1.32 to 2.32); P
      < 0.001) and vascular invasion (HR 1.63 (95 per cent c.i. 1.15 to 2.30); P <
      0.001). In younger patients (aged 75 years or less), who are more likely to be
      considered for chemotherapy, these two features showed independent prognostic
      significance but with higher HR values (1.96 for stage T4 and 2.73 for vascular
      invasion). Stage T4 and/or the presence of vascular invasion identified a 'poor'
      prognostic group, comprising 26.6 per cent of younger patients and with a 5-year
      survival rate of 71.2 per cent. The remaining 'good' prognostic group had a
      survival rate of 84.3 per cent at 5 years' follow-up. CONCLUSION: This study
      highlights the importance of accurate pathological assessment of tumour stage and
      vascular invasion for the prognostic stratification of patients with stage II
      colonic cancer. The results provide clarification of guidelines for the
      management of stage II disease in relation to recommendations for chemotherapy.

PMID- 16622902
TI  - Interstitial pneumonitis associated with infliximab therapy.
AB  - Interstitial pneumonitis is a well documented, rare complication of methotrexate
      (MTX). We describe a patient with rheumatoid arthritis (RA) taking MTX for more
      than 3 years who then developed severe interstitial pneumonitis after a third
      infliximab infusion. Other similar cases are reviewed. Infliximab may potentiate
      pulmonary toxicity of MTX.

PMID- 16622903
TI  - Quality of life and functional status in systemic sclerosis compared to other
      rheumatic diseases.
AB  - OBJECTIVE: To assess clinical factors associated with disability and physical
      health in patients with systemic sclerosis (SSc) compared to psoriatic arthritis
      (PsA), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) and
      healthy controls. METHODS: Eighty-two patients with SSc, 82 with PsA, 74 with
      SLE, 42 with RA, and 60 controls were recruited from various rheumatology clinics
      and underwent physical examination, tender point count, Health Assessment
      Questionnaire Disability Index (HAQ-DI) and Short Form-36 Health Survey (SF-36)
      assessments. RESULTS: SSc patients were younger and had shorter disease duration
      than the comparator groups. SSc patients with joint involvement had significantly
      poorer HAQ-DI scores than patients with PsA (1.43 vs 0.84; p < 0.05), and had
      higher visual analog scale pain scores than RA patients (1.37 vs 1.01; p < 0.05).
      The SF-36 Physical Component Summary and HAQ-DI score in SSc patients were
      adversely affected by joint involvement (p < 0.01, p < 0.001, respectively), >or=
      11 tender points (p < 0.01, p < 0.001), gastrointestinal (GI) involvement (p <
      0.01, p < 0.01), and high skin score (p = 0.02, p < 0.001). CONCLUSION: Physical
      health relating to quality of life is adversely affected in patients with SSc.
      Disability is associated with the presence of >or= 11 tender points, a high skin
      score, and joint and GI involvement. Joint involvement in SSc is more disabling
      than joint involvement in PsA; and patients with SSc experience more severe pain
      than patients with RA.

PMID- 16622904
TI  - A cohort study of cancer incidence in systemic sclerosis.
AB  - OBJECTIVE: To describe the incidence of cancer in a large cohort of patients with
      systemic sclerosis (SSc) and compare it to the Surveillance Epidemiology and End
      Results (SEER) cancer registries. METHODS: Cancer risk in a large cohort of
      patients with SSc followed at our institution was assessed. A total of 769
      patients with SSc who were followed between 1987 and 2002 were screened for the
      development of cancer. Standardized incidence ratios (SIR) for malignancies
      identified after diagnosis of SSc were calculated using the SEER cancer
      registries and stratified by sex. RESULTS: Ninety malignancies were diagnosed in
      769 patients followed at our institution between 1987 and 2002. Sixty-two
      malignancies were diagnosed after diagnosis of SSc in a total of 3,775 patient
      years of followup. Twenty-eight malignancies were diagnosed prior to diagnosis of
      SSc. The SIR for all cancers diagnosed after diagnosis of SSc was 1.55 (1.16
      1.93). The SIR for esophageal cancer was 15.9 (4.2-27.6) while that of
      oropharyngeal cancer was 9.63 (2.97-16.29). CONCLUSION: We identified an overall
      increase in the incidence of cancer in a cohort of patients with SSc compared to
      the general population, with statistically significant differences in the
      incidence of esophageal and oropharyngeal cancers.

PMID- 16622905
TI  - Socioeconomic status and risk of rheumatoid arthritis: a Danish case-control
      study.
AB  - OBJECTIVE: To examine whether markers of socioeconomic status (SES) are
      associated with risk of rheumatoid arthritis (RA), and if so, whether selected
      lifestyle-related factors could explain this association. METHODS: We conducted a
      frequency matched case-control study; subjects comprised 515 patients
      (participation rate 83%) attending rheumatology and internal medicine departments
      in Denmark, with recently diagnosed RA according to the American College of
      Rheumatology (ACR) 1987 classification criteria for RA (mean disease duration 2.3
      yrs), and 769 frequency-matched population controls (participation rate 64%).
      Information about SES and environmental exposure was obtained by structured
      telephone interview. Logistic regression analyses evaluated the role of markers
      of SES. RESULTS: Level of education was significantly inversely associated with
      risk of RA, with a 2-fold lower risk of RA among those with the longest formal
      education compared with those having the lowest level of education (multivariate
      odds ratio = 0.43, 95% confidence interval 0.24-0.76, p trend = 0.001). None of a
      series of studied lifestyle factors could explain this finding in multivariate
      logistic regression analyses. When dividing the RA cases into clinical subgroups,
      the inverse association with level of education was found to apply predominantly
      to rheumatoid factor (RF)-positive RA. CONCLUSION: The inverse association
      between level of education and risk of RF-positive RA was not explained by any of
      the examined lifestyle factors. RF-positive and RF-negative RA may be 2 distinct
      diseases with different etiologies, with unmeasured factors related to
      educational level predominantly associated with the risk of RF-positive RA.
      However, because mechanisms underlying referral to a hospital might be linked to
      educational level, our observation based on hospital-referred RA patients should
      be evaluated cautiously. The study stresses the importance of taking SES measures
      into account in studies that aim at identifying environmental risk factors for
      RA.

PMID- 16622906
TI  - Which variables best predict change in rheumatoid arthritis therapy in daily
      clinical practice?
AB  - OBJECTIVE: To determine in clinical practice which clinical status variables for
      rheumatoid arthritis (RA) are most closely associated with a change in disease
      modifying antirheumatic drug (DMARD) therapy. METHODS: A prospective monocenter
      study was conducted in 204 consecutive patients with RA. Rheumatologists recorded
      patient characteristics, treatments, and disease activity data [tender and
      swollen joint count (28), morning stiffness, visual analog scale (VAS) for pain
      (0-100 mm), patient global assessment and physician global assessment, Westergren
      erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)]. The
      rheumatologists decided whether or not to initiate or change treatment but were
      not informed that their decisions were part of the investigation. Logistic
      regression analysis was performed to evaluate which study variables best predict
      change in therapy. ROC analysis was used to obtain the cutoff value of the
      different composite indices (DAS28(ESR), DAS28(CRP), SDAI) for treatment change,
      as well as sensitivity and specificity. RESULTS: The variables that were
      predictive for a change in treatment were (in descending order): swollen joint
      count, morning stiffness, CRP, tender joint count, and patient global assessment.
      Composite index values associated with a decision to modify DMARD therapy were:
      DAS28(ESR) 4.2 (sensitivity 87%, specificity 70%); DAS28(CRP) 3.6 (sensitivity
      86%, specificity 78%); and SDAI 15 (sensitivity 90%, specificity 86%). The
      discriminative ability of SDAI was better than that of DAS28(CRP) or DAS28(ESR).
      CONCLUSION: In our study, swollen joint count was the variable with the greatest
      weight, which explains the observed better performance of SDAI.

PMID- 16622908
TI  - [Episiotomy: recommendations of the CNGOF for clinical practice (December 2005)].

PMID- 16622910
TI  - The study of neural network-based controller for controlling dissolved oxygen
      concentration in a sequencing batch reactor.
AB  - The design and development of the neural network (NN)-based controller
      performance for the activated sludge process in sequencing batch reactor (SBR) is
      presented in this paper. Here we give a comparative study of various neural
      network (NN)-based controllers such as the direct inverse control, internal model
      control (IMC) and hybrid NN control strategies to maintain the dissolved oxygen
      (DO) level of an activated sludge system by manipulating the air flow rate. The
      NN inverse model-based controller with the model-based scheme represents the
      controller, which relies solely upon the simple NN inverse model. In the IMC,
      both the forward and inverse models are used directly as elements within the
      feedback loop. The hybrid NN control consists of a basic NN controller in
      parallel with a proportional integral (PI) controller. Various simulation tests
      involving multiple set-point changes, disturbances rejection and noise effects
      were performed to review the performances of these various controllers. From the
      results it can be seen that hybrid controller gives the best results in tracking
      set-point changes under disturbances and noise effects.

PMID- 16622911
TI  - Disorders of ketone production and utilization.

PMID- 16622909
TI  - Adverse effects of antifungal therapies in invasive fungal infections: review and
      meta-analysis.
AB  - Amphotericin B is the main therapeutic agent for the treatment of invasive fungal
      infections; however, it is associated with significant toxicities that limit its
      use. Other systemic antifungal agents have been developed to improve tolerability
      while maintaining the efficacy profile of conventional amphotericin B. Fifty-four
      studies involving 9,228 patients were assessed for the frequency of adverse
      effects of the main systemic antifungal agents. While the results suggest that
      liposomal amphotericin B is the least nephrotoxic of the lipid formulations
      (14.6%), that conventional amphotericin B is the most nephrotoxic (33.2%), and
      that itraconazole is the most hepatotoxic (31.5%), the lack of standard
      definitions of antifungal-related adverse effects limits the validity of these
      results. Furthermore, heterogeneous patient pools and differing protocols make it
      difficult to draw direct comparisons between studies. With the advent of newer
      classes of systemic antifungal agents, future trials should conform to
      definitions that are universally applicable and clinically relevant to allow for
      such comparisons and to enable evidence-based decision-making.

PMID- 16622912
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 16622913
TI  - National Hormone and Peptide Program: peptide hormones, antisera and other
      reagents available.

PMID- 16622914
TI  - Patient Information Page from the Hormone Foundation. Prostate cancer and bone
      loss.

PMID- 16622915
TI  - Diffuse pigmented villonodular synovitis of the foot and ankle treated with
      surgery and radiotherapy.
AB  - We followed up seven patients with histologically confirmed diffuse pigmented
      villonodular synovitis in a prospective study between 1992 ans 2001. The mean age
      at diagnosis was 30.7 years. The patients underwent synovectomy, followed by
      radiotherapy with a total dose of 35 Gy in 20 fractions. In all cases, the
      excision was considered incomplete when examined histologically. At an average
      follow up of 24 (18-36) months, six patients reported better function and reduced
      levels of pain. One patient remained symptomatic but did not have a recurrence.
      We conclude that a combined approach to a primary pigmented villonodular
      synovitis of the foot and ankle may reduce the risk of recurrence without
      functional impairment.

PMID- 16622916
TI  - Current awareness in NMR in biomedicine.

PMID- 16622917
TI  - Imaging tagless DNA.

PMID- 16622919
TI  - Need for endoscopic removal of oesophageal coins in children was similar for
      strategies of immediate removal and watchful waiting.

PMID- 16622918
TI  - Use of 2% lidocaine gel during bladder catheterisation did not reduce procedure
      related pain in young children.

PMID- 16622920
TI  - Review: antibiotics are more effective than placebo for acute bacterial
      rhinosinusitis.

PMID- 16622921
TI  - Review: physical training increases cardiopulmonary fitness in asthma and does
      not decrease lung function.

PMID- 16622922
TI  - Paracetamol, non-steroidal anti-inflammatory drugs, and combination treatment did
      not differ for pain relief after musculoskeletal injury.

PMID- 16622923
TI  - Review: dietary intervention plus exercise is no better than dietary intervention
      alone for inducing long term weight loss.

PMID- 16622924
TI  - Review: dietary plus pharmacological intervention (orlistat or sibutramine)
      induces long term weight loss in overweight or obese adults.

PMID- 16622925
TI  - Review: dietary advice improves dietary intake and reduces cardiovascular risk
      factors.

PMID- 16622926
TI  - Inhaled insulin added to or replacing 2 oral agents reduced haemoglobin A1c
      concentrations in type 2 diabetes.

PMID- 16622927
TI  - Review: antibiotic prophylaxis reduces mortality in patients with neutropenia.

PMID- 16622928
TI  - Review: once daily LMWH is as effective as twice daily LMWH for initial treatment
      of venous thromboembolism.

PMID- 16622929
TI  - Supplemental perioperative oxygen at 80% FIO2 reduced surgical site infections in
      elective colorectal surgery.

PMID- 16622930
TI  - Management of critically ill patients with a pulmonary artery catheter did not
      reduce all cause mortality.

PMID- 16622931
TI  - Review: hospital based case management does not reduce length of hospital stay or
      readmissions in adults.

PMID- 16622932
TI  - A telephone intervention reduced combined all cause mortality or admission for
      worsening heart failure in chronic heart failure.

PMID- 16622933
TI  - Review: existing evidence does not support nurse led interventions in chronic
      obstructive pulmonary disease.

PMID- 16622934
TI  - An operational definition of frailty predicted death and other adverse outcomes
      in older women.

PMID- 16622935
TI  - Educational outreach visits to primary care nurses improved tuberculosis
      detection and treatment of obstructive lung disease.

PMID- 16622936
TI  - A multifaceted intervention reduced antimicrobial prescriptions for suspected
      urinary tract infections in nursing home residents.

PMID- 16622937
TI  - The complex self perceptions and relationships of patients who attended free
      clinics affected their attendance and ability to benefit from care.

PMID- 16622938
TI  - Failure of a Web-based educational tool to improve residents' scores on the
      American Board of Surgery In-Training Examination.
AB  - HYPOTHESIS: Usage of a Web-based educational tool will improve residents' scores
      on the American Board of Surgery In-Training Examination (ABSITE). DESIGN: Before
      and after trial. SETTING: Academic surgical residency in a tertiary care
      university hospital. PARTICIPANTS: Nineteen postgraduate year 1 (PGY1) and PGY2
      residents. INTERVENTION: All PGY1 and PGY2 residents were given unlimited access
      to a Web-based educational tool aimed at early-level residents in surgery. The
      educational tool covers the basic science of surgery and basic concepts of
      clinical surgery and uses a variety of educational techniques (readings, problem
      based learning, case-based learning, and practice tests). Although residents were
      encouraged to complete the learning package, they were not required to do so.
      MAIN OUTCOME MEASURES: The ABSITE scores and changes in ABSITE scores were
      compared with the amount of time residents spent using the program and the number
      of tutorials completed. RESULTS: There was no significant difference in ABSITE
      scores before or after the use of the Web-based educational tool. There was no
      significant relationship between use of the tool (either in total time or total
      tutorials) and ABSITE score. For PGY2 residents, there was a negative
      relationship between total time spent on the program and ABSITE score (linear
      regression analysis best-fit slope, -0.20 +/- 0.1; r2 = 0.33) and total tutorials
      completed and ABSITE score (linear regression analysis best-fit slope, -0.34 +/-
      0.22; r2 = 0.25). CONCLUSION: There was no demonstrable beneficial effect of a
      Web-based educational tool on cognitive knowledge of residents as measured by
      ABSITE scores.

PMID- 16622939
TI  - [The cardiology standard is no flash in the pan. Conversation with Prof. Erland
      Erdmann, Koln].

PMID- 16622940
TI  - Why aren't optometrists dispensing more plano sunglasses?

PMID- 16622941
TI  - When is it time to bring an associate into a practice?

PMID- 16622942
TI  - Tax savings through cost segregation.

PMID- 16622943
TI  - Health and Human Services--Office of Inspector General studies find misuse of
      Modifiers 59, 25.

PMID- 16622945
TI  - Controlled medication agreement.

PMID- 16622952
TI  - Residues of DDT and HCH in wheat samples collected from different states of India
      and their dietary exposure: A multicentre study.
AB  - Under a multicentre study conducted by the Indian Council of Medical Research,
      1712 samples of wheat grain/flour were collected from urban and rural areas in 11
      states representing different geographical regions of India. These samples were
      analysed for residues of DDT (2,2-bis (p-chlorophenyl)-1,1,1-trichloro ethane)
      and different isomers of HCH (1,2,3,4,5,6-hexachloro cyclohexane, a mixture of
      isomers) by gas-liquid chromatography. Residues of DDT were detected in 59.4% of
      1080 samples of wheat grain and in 78.2% of 632 samples of wheat flour. Different
      isomers of HCH were present in about 45-80% of the samples of wheat grain/flour.
      Medians of DDT and total HCH, respectively, for pooled samples of wheat grain
      were 0.013 and 0.035 mg kg(-1), while those for wheat flour were 0.01 and 0.02 mg
      kg(-1). Estimated daily intakes of DDT and different isomers of HCH through the
      consumption of wheat contaminated at their median and 90th percentiles
      constituted a small proportion of their acceptable daily intakes. Amongst the
      pesticide residues analysed, statutory maximum residue limits have been fixed
      only for gamma-HCH in wheat in India, as 0.1 mg kg(-1) in wheat grain and zero in
      wheat flour. Residue levels of gamma-HCH exceeded these maximum residue limits in
      five of 1080 samples of wheat grain and in 340 of 632 samples of wheat flour. The
      failure to meet the requirement of the gamma-HCH maximum residue limit in large
      number of wheat flour samples was attributed to the fixation of practically
      unachievable zero limit. Comparing the previous studies and the present one, the
      levels of residues of DDT and HCH in wheat were significantly decreased.

PMID- 16622953
TI  - Genetic engineering regulation in Australia: an 'archaeology' of expertise and
      power.

PMID- 16622944
TI  - N-Glycans carried by Tamm-Horsfall glycoprotein have a crucial role in the
      defense against urinary tract diseases.
AB  - Tamm-Horsfall glycoprotein (THGP), produced exclusively by renal cells from the
      thick ascending limb of Henle's loop, is attached by a glycosyl
      phosphatidylinositol (GPI)-anchor to the luminal face of the cells. Urinary
      excretion of THGP (50-100 mg/day) occurs upon proteolytic cleavage of the large
      ectodomain of the GPI-anchored form. N-Glycans, consisting of a large repertoire
      of sialylated polyantennary chains and high-mannose structures, account for
      approximately 30% of the weight of human urinary THGP. We describe: (i) the
      involvement of urinary THGP high-mannose glycans in defense against infections of
      the urinary tract, caused by type-1 fimbriated Escherichia coli, which recognize
      high-mannose structures, (ii) the role of GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1
      4GlcNAcbeta1-3Gal (Sd(a) determinant) carried by human THGP in protecting the
      distal nephron from colonization of type-S fimbriated E. coli which recognise
      NeuAcalpha2-3Gal, (iii) the inhibitory effect of sialylated THGP on crystal
      aggregation of calcium oxalate and calcium phosphate, thus preventing
      nephrolithiasis. Finally, we outline the importance of N-glycans in promoting the
      polymerization of THGP, a process resulting in the formation of homopolymers with
      an M(r) of several million in urine. Since THGP defense against diseases of the
      urinary tract mainly consists in binding damaging agents, its ability to behave
      as a multivalent ligand significantly enhances this protective role.

PMID- 16622955
TI  - The Louisiana "human embryo" statute revisited: reasonable recognition and
      protection for the in vitro fertilized ovum.

PMID- 16622954
TI  - Asilomar's legacy in Aotearoa New Zealand.

PMID- 16622956
TI  - The process of regulating assisted reproductive technologies: what we can learn
      from our neighbors--what translates and what does not.

PMID- 16622957
TI  - Reproductive technologies: where are we headed?

PMID- 16622958
TI  - The new genetic technologies: new options, new hope, and new challenges.

PMID- 16622959
TI  - In re E.G., a Minor: death over life: a judicial trend continues as the Illinois
      Supreme Court grants minors the right to refuse life-saving medical treatment.

PMID- 16622960
TI  - Life and death decisions: a reply to Judge Peccarelli.

PMID- 16622961
TI  - A moral dilemma: the role of judicial intervention in withholding or withdrawing
      nutrition and hydration.

PMID- 16622962
TI  - New York v. Sullivan: shhh ... don't say the "a" word! Another outcome-oriented
      abortion decision.

PMID- 16622963
TI  - A response to Irwin Kramer's reply.

PMID- 16622964
TI  - When is personal data rendered anonymous? Interpreting Recital 26 of Directive
      95/46/EC.

PMID- 16622965
TI  - Autonomy and audit--striking the balance.
AB  - The Data Protection Act 1998 purports to implement European legislation which
      aims to protect the privacy of individuals. There were such concerns about the
      implications of the Act for certain research and audit that it became necessary
      to enact further legislation to enable such essential activities to continue.
      Although this empowers the Secretary of State for Health to approve proposals for
      these purposes, there should still be a requirement that the use of identifiable
      personal information without consent must be justified on compelling public
      interest grounds. It is this that can confound those seeking to rely on such
      justification. There can either be too cavalier an approach to the issue, and/or
      there is little sense of what considerations should come into play. This paper
      attempts to highlight some of the difficulties that are theoretically raised by
      some audit activities and set out the legal framework within which they must
      operate. However, the key focus is on how ethical considerations might inform the
      public interest argument.

PMID- 16622966
TI  - Public health powers in relation to infectious tuberculosis in England and
      France: a comparison of approaches.
AB  - This article examines the legal responses to infectious tuberculosis in England
      and France. Given that tuberculosis has re-emerged as a public health threat in
      both countries, the differing jurisprudence and legal frameworks of disease
      control in the two jurisdictions warrant examination. Two questions arise in that
      respect: firstly, what is the role of the State in the protection of public
      health in the context of tuberculosis, and secondly, to what extent can the law
      intervene to coerce individuals to undertake health measures for the protection
      of society at large. These issues reveal the tensions that exist between the
      individual and public interest. France and England differ greatly in their
      responses to such tensions. Paradoxically, France, that has traditionally
      embraced strong State intervention, has been reluctant to curtail individual
      freedoms for the benefit of public health. Conversely, England, that has tended
      to be more closely associated with liberalism, has been ready to accept and even
      promote restrictions to individual freedoms in the collective interest.

PMID- 16622967
TI  - Wrongful life: the problem of causation.
AB  - The paper considers the status of the wrongful life action particularly in the
      light of the recent acceptance of such actions in continental Europe. It is
      considered that the hurdle of causation is still not adequately overcome in these
      cases and, in a search for an answer to the difficulty, the author re-examines
      the Canadian case of Cherry v Borsman. This case was originally thought of as one
      of wrongful life associated with a negligently performed abortion and the paper
      attempts to overcome the problems of causation by comparing and contrasting the
      roles of the genetic counsellor and the abortionist. While the attempt is by no
      means wholly successful, it also serves to draw attention to some significant
      differences between wrongful life actions based on physical and mental disability
      in the neonate.

PMID- 16622968
TI  - Pre-implantation genetic diagnosis, tissue typing and beyond: the legal
      implications of the Hashmi case.
AB  - The legality of pre-implantation genetic diagnosis (PGD) has recently been
      confirmed by the Court of Appeal in the Hashmi case, based on a purposive
      construction of the statute. The court went on to declare tissue typing lawful
      and strained the wording of the statute in order to do so. The Hashmi case
      confirms that it would be lawful for the HFEA to license tissue typing in the
      absence of PGD. However, the HFEA only licenses tissue typing where PGD is also
      indicated, on the basis of a blanket application of the welfare of the child test
      set out in S 13 (5). This policy can be criticised. Firstly, a blanket approach
      to S 13 (5) is not appropriate. Secondly, the HFEA is applying the test too
      strictly when compared to the 'best interests' test which would govern the
      situation were an existing child to be a potential donor. Thirdly, by licensing
      tissue typing in the Hashmi case, where it was the primary reason for testing,
      the HFEA has undermined the argument that it can be justified only in cases where
      it is ancillary to PGD. These arguments, coupled with human rights arguments,
      based on Art 8 and Art 12, could be used to challenge the legitimacy of the
      HFEA's policy. The restriction on tissue typing to cases where PGD is also
      indicated is not ethically justified. It offers the same direct benefit to the
      embryo as PGD, namely selection for implantation. PGD does not cure the relevant
      condition so offers no additional benefit in a causative sense. Moreover, the
      Kantian injunction against treating people solely as means is not breached where
      the child will be wanted for its own sake, as well as for its potential as a cord
      blood donor.

PMID- 16622969
TI  - Improved formula for oral rehydration salts to save children's lives.

PMID- 16622970
TI  - WHO launches new stop TB strategy to fight the global tuberculosis epidemic.

PMID- 16622971
TI  - Excessive risk disclosure: the effects of the law on medical practice.
AB  - This article examines the debate surrounding the challenging concept of informed
      consent. It argues whilst the English courts have effectively excluded the use of
      the tort of battery as an appropriate mechanism for protecting a patient's right
      to self-determination, they have left the law in a state of flux due to the
      uncertainties associated with categorising similar claims within negligence where
      the onus is on risk disclosure. This confusion may stem firstly from the fact
      that medical practitioners are unsure exactly which risks to disclose, and
      secondly, from the way in which both doctors and patients perceive the consent
      process. The paper suggests this disorder may be having a detrimental effect on
      medical practice as medical practitioners are taking it upon themselves to
      disclose excessive information, which patient's may not want or need. A
      suggestion is also made that in these situations, in order that the law truly
      respects self-determination, consideration must be given to the patient's desire
      to waive their right to informed consent.

PMID- 16622972
TI  - Americas, South-East Asia and Western Pacific regions on track to reach
      tuberculosis control targets.

PMID- 16622973
TI  - Global measles deaths plunge by 48% over past six years.

PMID- 16622974
TI  - Viet Nam eliminates maternal and neonatal tetanus.

PMID- 16622975
TI  - 400 million children deprived of safe water.

PMID- 16622976
TI  - Harmonizing the international regulation of embryonic stem cell research:
      possibilities, promises and potential pitfalls.
AB  - Despite near unanimous global opposition to human reproductive cloning, the
      United Nations has been unable to reach a consensus as to how cloning practices
      should be regulated at the international level. As a result, the U.N. objective
      of establishing binding international regulations governing cloning and stem cell
      research has yet to be achieved. Given the lack of consensus that exists within
      the global community on this topic, it seems that any attempt to harmonize the
      international regulation of cloning and stem cell science will face important
      obstacles. This paper seeks to illuminate the particular challenges to
      harmonizing international laws and policies related to stem cell research and
      human cloning, and to investigate potential methods for overcoming these
      challenges. By drawing on two other areas in which regulatory harmonization has
      been attempted, namely: environmental and human safety aspects of international
      trade, and pharmaceutical research and development, we study approaches to global
      regulatory harmonization. We conclude that while the challenges to harmonization
      are diverse and important, so too are the benefits of establishing uniformity in
      approaches to stem cell research worldwide. This paper proposes a model for
      harmonizing the regulation of stem cell research that focuses on broader norms
      and principles rather than specific rules. It further recommends that such
      harmonization should occur through a process initiated and developed by an
      independent international agency marked by diversity, both in terms of the
      cultural identities and perspectives represented, and the interdisciplinary
      expertise of its members.

PMID- 16622977
TI  - Reported outcome factors for hepatic metastasectomy.

PMID- 16622978
TI  - Role of new three-dimensional image analysis techniques in planning of live donor
      liver transplantation, liver resection, and intervention.

PMID- 16622979
TI  - Surgical techniques for liver resection.

PMID- 16622980
TI  - Anesthetic management for liver resection.

PMID- 16622981
TI  - Giving the reasonable patient a voice: information disclosure and the relevance
      of empirical evidence.
AB  - In England the standard of risk disclosure required of doctors to avoid liability
      in negligence is governed by the Bolam test. The test is determined by what would
      be accepted as reasonable by the responsible doctor. Although able to lay down an
      independent standard, the courts have usually been guided by the medical expert's
      evidence. The judge's duty to scrutinise expert evidence was reaffirmed by the
      recent House of Lords ruling in Bolitho v City and Hackney HA. In Pearce v United
      Bristol Healthcare NHS Trust, Lord Woolf MR confirmed that this also applied to
      risk disclosure. Brazier & Miola argue that Pearce effectively introduces the
      prudent patient standard into English law. This paper examines that claim and
      considers whether it is justified by the Pearce judgment. The implications of
      Pearce are explored and, given the appeal to the concept of a material risk, I
      discuss the relevance of empirical research to determining the standard of
      disclosure. Finally, a small piece of empirical work is presented as an
      illustration of the pros and cons of such an approach and as a possible
      springboard for future research.

PMID- 16622982
TI  - Pancreatic neuroendocrine tumors: overview of recent advances and diagnosis.

PMID- 16622983
TI  - Treatment of isolated neuroendocrine liver metastases.

PMID- 16622984
TI  - Therapy with radiolabeled somatostatin peptide analogs for metastatic
      neuroendocrine tumors.

PMID- 16622985
TI  - The new French resistance: commodification rejected?

PMID- 16622986
TI  - Therapeutic and palliative options for diffuse neuroendocrine metastatic disease.

PMID- 16622987
TI  - More subject and less human: the pain-filled journey of human subjects protection
      ... and some differences in the United States and the European Union.

PMID- 16622988
TI  - Euthanasia.

PMID- 16622989
TI  - Using our best judgment in conducting human research.
AB  - The federal regulations of human research were written to permit the use of
      discretion so that research can fit the circumstances under which it is
      conducted. For example, the researcher and institutional review board (IRB) could
      waive or alter some informed consent elements if they deem this the morally and
      scientifically best way to conduct the research. To do so, however, researchers
      and IRBs would first have to use mature moral and scientific judgment. They might
      also have to rely on empirical research to discover the most effective way to act
      on their moral sense (e.g., to discover how best to approach potential research
      participants and explain the nature and purpose of the research participation for
      which they are being recruited, to ensure comprehension and competent decision
      making). On discovering the most ethical way to proceed, they would then need to
      look to the federal regulations of human research to discover how to document
      their decision and justify it within that somewhat flexible regulatory structure.
      Unfortunately, many IRBs and researchers fail to take these sensible steps to
      solve ethical problems and proceed immediately to a default requirement of the
      regulations that places science at odds with the regulations and, ostensibly,
      with ethics. The following articles in this special issue are about the process
      of learning to engage in ethical problem solving and using the flexibility
      permitted by the federal regulations. These articles extricate researchers from
      the mindset that has gotten them into trouble, and, ideally, provoke them to use
      mature common sense and moral judgment.

PMID- 16622991
TI  - [High function PACS utilizing Osirix, an open source software].

PMID- 16622990
TI  - The problem of privacy in transcultural research: reflections on an ethnographic
      study in Sri Lanka.
AB  - Western laws and codes of ethics frequently require that private health
      information be treated confidentially. However, cross-cultural research shows
      that it is not always easy to determine what members of a culture consider to be
      private or how they wish private information to be handled. This article begins
      by presenting an ethnographic study of patient-healer relationships in Sri Lanka;
      researchers were surprised to find that participants' views of health and privacy
      differed greatly from typical Western views, and that the privacy protections
      they had put in place caused discomfort among participants. Building on this
      ethics case study, the article explores two main questions. First, can a single
      definition of privacy possibly do justice to the cultural variations that exist,
      or does a conceptual definition inevitably run the risk of ethnocentrism? Second,
      to what extent is strict compliance with research regulations or ethics codes
      ethically justifiable when following the rules will obviously cause unease in
      international participants?

PMID- 16622992
TI  - Her Royal Highness Princess Maha Chakri Sirindhorn: her activities in humanity
      and medicine.
AB  - Her Royal Highness Princess Maha Chakri Sirindhorn, the Executive Vice-President
      of the Thai Red Cross Society has followed the footsteps of her fore-bears,
      carrying the noble humanitarian work they began, particularly the work of the
      Thai Red Cross society and the Faculty of Medicine, Chulalongkorn University. Her
      contributions have been a benefit to all, and she has earned great love and is
      held in high esteem by her people. Her ideas, thoughts, words, and activities
      have been of immense value to the faculty in both tangible and intangible ways. A
      selfless, dedicated women who is willing to make sacrifices for the common good,
      Her Royal Highness serves as a model humanitarian for the staff of the Faculty of
      Medicine, Chulalongkorn University, whose morale she has boosted and whose
      operations she has planned with the foresight ofa first-class administrator. Her
      devotion to the Thai Red Cross, and thus her devotion to her people, have indeed
      made her the royal gem within Thai hearts, with sparkling brilliance of her
      humanitarian deeds instilling the warmth of her love in our spirits.

PMID- 16622993
TI  - Outcome of pediatric hematopoietic stem cell transplantations from Thai unrelated
      donors matched with high-resolution HLA typing.
AB  - The authors evaluated the outcome of ten children given hematopoietic stem cell
      transplantations from Thai unrelated donors (URD-HSCT) selected using DNA high
      resolution typing of both HLA class I and II loci. Six patient/donor pairs (60%)
      were fully matched; four (40%) were 5/6 matched. Patients had either non
      malignant (n=9) or malignant (n=1) diseases. In most cases, graft-versus-host
      disease (GVHD) prophylaxis composed of cyclosporine and short-term methotrexate.
      The probability of hematopoietic recovery at day 30 was 90%. The cumulative
      probability of acute GVHD and of chronic GVHD equaled 44.4 and 0%, respectively.
      Three patients died of transplant-related complications. The probability of
      transplant-related mortality (TRM) at 30, 100, and 180 days were 10, 30, and 30%,
      respectively. The overall and disease-free survival rates were 70 and 70%,
      respectively. URD-HSCT with donor selection based on high-resolution HLA typing
      is associated with a low incidence of both severe acute GVHD and graft failure.
      The observed outcome is comparable to that of children transplanted from HLA
      identical siblings.

PMID- 16622994
TI  - The prevalence of varicella-zoster virus infection in normal healthy individuals
      aged above 6 months.
AB  - The prevalence of varicella-zoster virus (VZV) infection was studied by
      determining the presence of IgG antibody to VZV (anti-VZV IgG) using ELISA
      method. Three hundred and fifty sera collected from Thai healthy individuals aged
      above 6 months (mean age +/- standard deviation = 14.9 +/- 11.4) were tested, the
      prevalence of VZV infection was 64.6% (225/350). All samples were randomly
      sampling from healthy children and blood donors who visited the hospital and
      clssified into 7 groups, 50 samples each, according to their age, i.e., group 1;
      6 months-3 years, group 2; 4-6 years, group 3; 7-9 years, group 4; 10-14 years,
      group 5; 15-19 years, group 6; 20-24 years and group 7; above 25 years. The
      prevalence of VZV infection were 12%, 42%, 64%, 70%, 78%, 84% and 100%
      respectively. The mean amount of anti-VZV IgG among groups of positive VZV
      infection (225 samples) was 86.8 +/- 29.7 unit/ml. The mean amount of anti-VZV
      IgG was highest in 6 months-3 years age group (113.6 +/- 39.2 unit/ml).
      Significant difference of the mean amount of anti- VZV IgG was found between
      group 1, 3, 6 and other groups (p-value < 0.05). There was a correlation between
      history of varicella and the presence of anti-VZV IgG in the serum. 95.3% of
      individuals with positive history has already had the antibody. The important
      associated factors that might involve VZV infection were age, number of members
      in family and place of exposure to VZV infection. Other factors, such as sex and
      income did not show any association to VZV infection.

PMID- 16622995
TI  - Infective endocarditis in pediatric patients: an eighteen-year experience from
      King Chulalongkorn Memorial Hospital.
AB  - OBJECTIVES: To review the clinical features and outcome of the pediatric patients
      diagnosed with infective endocarditis (IE) at King Chulalongkorn Memorial
      Hospital over an 18-year period. MATERIAL AND METHOD: From January 1987 to
      December 2004, 57 pediatric patients; 28 females and 29 males, age ranged from 2
      months to 15 years, mean of 8.64 +/- 3.82 years, classified as "definite" IE
      according to the Duke criteria were reviewed. RESULTS: Of the 57 patients, 42
      patients (74%) had underlying congenital heart diseases, 7 patients (12%) had
      underlying rheumatic heart disease, 8 patients (14%) had previously normal heart.
      Nine patients had history of previously palliative or corrective surgery. Blood
      cultures were positive in 26 patients (46%). Streptococci and staphylococci were
      the most commonly isolated organisms. Two-dimensional echocardiography
      demonstrated vegetations in 56 patients (98%). The location of the vegetations
      was in the right heart in 30 patients (54%) and in the left heart in 26 patients
      (46%). Complications occurred in 28 patients (49%). Common complications included
      congestive heart failure, cerebral emboli, septic shock, and mycotic aneurysm.
      The overall mortality was 11% (6 patients). By statistical analysis, vegetations
      in the left heart had a higher incidence of complication than that in the right
      heart. The vegetation size of > or =10 mm had a significant higher incidence of
      embolic events. CONCLUSION: The clinical features and outcomes of the present
      study have a similar pattern as the earlier studies. The rates of complications
      and mortality are still high.

PMID- 16622996
TI  - Children with clinical central diabetes insipidus at King Chulalongkorn Memorial
      Hospital.
AB  - OBJECTIVES: To determine the etiologies and associated endocrine disorders in
      children with central diabetes insipidus (DI). MATERIAL AND METHOD: The authors
      retrospectively reviewed the medical records of children with central DI, who
      were admitted at department of Pediatrics, King Chulalongkorn Memorial Hospital,
      between 2000 and 2004. Aims of this study were to identify the etiology of
      central DI in children and also described the anterior pituitary hormone
      insufficiencies which may occur. RESULTS: Of the total 51 patients, 27 patients
      were males and 24 were females. Intracranial tumors produced DI in 36 children
      (70.6%), but 17 of these 36 children (47.22%) had DI before surgical removal of
      the tumors. Fifteen patients (29.4%) had DI from non-tumor causes, which include
      idiopathic in 2 patients (13.5%), terminal events in 4 patients (26.8%), central
      nervous system (CNS) infection in 5 patients (33.3%), CNS anomalies in 2 patients
      (13.5%), Kabuki syndrome in 1 patient (6.6%), head injury in 1 patient (6.6%).
      Anterior pituitary function was evaluated in all tumor group and 8 patients of
      non-tumor group. In intracranial tumor group, growth hormone deficiency (GHD) was
      documented in 14 from 22 patients (63.6%), secondary adrenal insufficiency in 13
      from 20 patients (65%), central hypothyroid in 27 from 36 patients (75%),
      hyperprolactinemia in 5 from 8 patients (62.5%). CONCLUSION: The most common
      etiology of central DI is intracranial tumor, and at least 50% of them have
      clinical features suggesting central DI before surgery. More than 60% have
      associated anterior pituitary hormone insufficiency.

PMID- 16622997
TI  - Pediatric heart surgery waiting time in Thailand and its effect on mortality: A
      cooperative study from Chulalongkorn, Children and Chiang Mai University
      hospitals.
AB  - BACKGROUND: Thai children who need cardiac surgery are often put on a waiting
      list. The waiting time and mortality during waiting have not been previously
      systematically studied. MATERIAL AND METHOD: A cooperative study was conducted at
      King Chulalongkorn Memorial hospital (Chula), Children hospital (CH), and Chiang
      Mai University hospital (CMU). The status of children who were referred for
      cardiac surgery at these hospitals in the year 1999-2000 (Chula and CMU) and the
      year 2000 (CH) were analyzed by Kaplan-Meier survival curve. The patients who
      lost to follow up and could not be contacted were censored at the time of last
      clinic visit. Log-Rank test was used to compare the survival curve and waiting
      time between three hospitals. RESULTS: The averaged annual referrals for cardiac
      surgery at the three hospitals were 846 cases (205 for Chula, 462 for CH and 179
      for CMU). Mean age was 4.3 +/- 4.2 years and 51% were male. Follow up data were
      complete in 96.3%. Surgical procedures were correction of simple shunt lesions
      (ASD, VSD, AV canal) in 33.9%, close heart surgery (PDA ligation, coarctation
      repair, BT shunt) in 29.9%, total repair TOF in 19.6%, complex surgery in neonate
      and infants (arterial switch, TAPVR repair, Norwood procedure, truncus and
      interrupted aortic arch repair) in 4.2% and others in 12.3%. Median waiting time
      was 195 days and was significantly different between the three hospitals (p <
      0.01). Mortality while waiting were approximately 5% at 2 years at Chula and CH,
      which was significantly higher than CMU (0%, p = 0.02). Further analysis revealed
      difference in age (lower Chula than CH than CMU) and types of surgery (more
      complex at Chula and CH) which may be the causes for difference in the mortality
      observed. CONCLUSION: Waiting time for cardiac surgery for children in Thailand
      is long and should be viewed as a problem in public health policy. Optimal
      waiting time at each hospital may not have to be the same, depending on the type
      and severity of the disease seen at each particular center Attempt should be made
      to solve this problem at the national level.

PMID- 16622998
TI  - The association of co-expression of CD44v4/MMP-9 with different nodal status in
      high-grade breast carcinoma patients.
AB  - BACKGROUND: Breast carcinoma is one of the most common tumors in female patients,
      and its metastasis is a major cause of death. An experimental model has recently
      found the association of CD44 with MMP-9 that facilitates tumor cell invasion and
      metastasis. MATERIAL AND METHOD: The CD44v4 and MMP-9 were performed on tissue in
      paraffin blocks of 50 cases of high-grade breast carcinoma with node positive and
      50 cases with node negative. RESULTS: Increased expression of MMP-9(60%)
      significantly observed in high-grade breast carcinoma patients with node positive
      (p = 0. 004), whereas CD44v4 displays no significant difference between the two
      groups (p-value = 0.81). Significant co-expression of CD44v4+ / MMP-9+ (46%) was
      observed and correlated with node-positive patients whereas the CD44v4+ / MMP-9-
      (54%) express in node-negative patient (p-value = 0.01). CONCLUSION: The solely
      expression of CD44v4 does not associate with node status. MMP-9 plays an
      important role to enhance breast carcinoma cell invasion and associates with
      lymph node metastasis. The combined expression of CD44v4 (overexpression) and
      derangement of MMP-9 expression was significantly associated with nodal status.

PMID- 16622999
TI  - A retrospective study of colonic polyps in King Chulalongkorn Memorial Hospital.
AB  - To evaluate and classify polyps from colon in Thai patients, the authors
      retrospectively analyzed the 776 polyps from 696 subjects in King Chulalongkorn
      Memorial Hospital during the past five-year period from 1999 to 2003. All colonic
      polyps were included in the study. There were 461 (59%) male and 315 (410%)
      female with the mean age of 51 years. Non-neoplastic and neoplastic polyps were
      documented 50% each. Hyperplastic polyp was the most frequent diagnosis (39%),
      followed by tubular adenoma (36%). According to neoplastic polyp, 8%, 3%, and 14%
      cases were identified as high-grade dysplastic change, intramucosal carcinoma,
      and invasive carcinoma, respectively.

PMID- 16623000
TI  - Can a single dose corticosteroid reduce the incidence of post-ERCP pancreatitis?
      A randomized, prospective control study.
AB  - BACKGROUND: Acute pancreatitis is one of the complications after Endoscopic
      retrograde cholangio pancreatography (ERCP) and it could be fatal. Several drugs
      were used to prevent or decrease this complication. Corticosteroid is one of the
      medications which may have such potential. It is affordable and available
      everywhere. OBJECTIVES: To compare the incidence of post-ERCP pancreatitis in
      patients receiving single dose corticosteroid prior to the procedure with that of
      the control group . RESEARCH DESIGN: A prospective randomized controlled double
      blinded study. MATERIAL AND METHOD: A total of 120 patients were randomized to
      receive either intravenous hydrocortisone 100 mg. or normal saline 1 hour prior
      to the procedure. The serum amylase levels were recorded 4 and 24 hours after the
      procedure. Abdominal pain and back pain were also recorded. Patients were
      diagnosed as having post-ERCP pancreatitis if ones had new or worsened epigastric
      pain with or without radiation to the back combined with elevation of serum
      amylase more than 2.5 times the upper limit. RESULTS: The overall incidence of
      pancreatitis was 6.67% with 1.64% in the study group compared with 11.86% in the
      control group (p = 0.031). The groups were similar with regard to age, gender,
      type of procedure performed (diagnostic or therapeutic), difficulty of
      cannulation, concentration of contrast media and pre operative amylase level.
      CONCLUSION: The results of the present trial indicate that hydrocortisone could
      reduce the risk of post-ERCP pancreatitis.

PMID- 16623001
TI  - Acute mesenteric ischemia: still high mortality rate in the era of 24-hour
      availability of angiography.
AB  - BACKGROUND: Acute mesenteric ischemia (AMI) is a serious condition with high
      mortality rate due to difficult and late diagnosis. Early and aggressive
      evaluation in high risk patients by mesenteric angiography is the key to the
      reduction in mortality rate. However; many physicians hesitated to perform it
      because of its availability, the risk of complications and high negative results.
      This study reviewed outcome of AMI in term of mortality rate, factors associated
      with mortality and the rate of angiography in high risk patients. MATERIAL AND
      METHOD: The clinical data of the patients who were diagnosed as AMI were
      retrospectively reviewed. The clinical outcome was recorded and the factors
      associated with mortality were analysed. RESULTS: Thirty-five patients were
      enrolled into this study during 5 years. The mortality rate was 74.3%. There were
      22 high risk patients for AMI. The rate of angiography performed in this group
      was 4.5% (1/22). The factors associated with mortality were age more than 60
      years, patients with peritonitis, hypotension, arterial cause, time interval
      between admission and operation or treatment more than 24 hours, bowel gangrene
      >100 cms. However all these factors were not statistically significant.
      CONCLUSION: The mortality rate of AMI is still high even at the tertiary hospital
      where the angiography is available 24 hours. To decrease the mortality rate, the
      physicians must have the high index of suspicion in high risk patients and do not
      hesitate to perform early mesenteric angiography.

PMID- 16623002
TI  - Incidence of corona mortis; preperitoneal anatomy for laparoscopic hernia repair.
AB  - The present study 66 half pelvis of cadaver for vascular structure called corona
      mortis, vessel that connect between external iliac and internal iliac system. The
      vessel was found 77.27% and the incidence of aberrant is 13.6%. The average
      distance from symphysis pubis to the vessel is 5.28 cm and distance above
      superior pubic rami is 1.37 cm.

PMID- 16623003
TI  - Risk factors associated with major intraoperative blood loss in hepatic resection
      for hepatobiliary tumor.
AB  - BACKGROUND AND PURPOSE: Hepatic resection is the mainstay treatment of
      hepatobiliary tumor Nowadays, mortality is less than 6%. However, morbidity is
      still high. Bleeding is one of the most common problems during hepatic resection
      which can sometimes lead to catastrophe. The purpose of the present study was to
      investigate the risk factors associated with major blood loss during hepatic
      resection for hepatobiliary tumor. MATERIAL AND METHOD: A total of 69 consecutive
      patients who underwent elective hepatic resection for hepatobiliary tumor from
      May 2002 to April 2004 were enrolled into this retrospective study. The Patients
      were divided into 2 groups(group I and II) according to the intraoperative blood
      loss. Patients who had a blood loss of more than 1000 ml were defined as the
      major blood loss group(group I). Thirteen variable factors were analyzed to
      determine the risk of major intraoperative blood loss. Operative outcomes between
      the two groups were also compared. RESULTS: Of the sixty-nine patients, 36
      patients were in group I and 33 patients were in group II. 75% of the patients in
      group I and 36.4% of the patients in group II were transfused. Median blood
      transfusion in group I and II were 3 and 0 units of packed red cell. Univariate
      analysis showed tumor size, extent of hepatic resection, tumor pathology and
      operative time were factors affecting major intraoperative blood loss. However,
      multivariate analysis showed only operative time and tumor size to be independent
      risk factors. Patients in group I had higher surgical morbidity and prolonged
      hospital stay compared with patients in group II. CONCLUSION: Blood loss is still
      a major concern in performing hepatic resection. From the present study, tumor
      size and operative time are the independent factors affecting major
      intraoperative blood loss. Proper screening or a surveillance program may enhance
      the chance to find small tumors. Refined operative techniques such as anterior
      approach and liver hanging would facilitate resection for large right sided
      tumors.

PMID- 16623004
TI  - Laparoscopic versus open surgery for rectosigmoid and rectal cancer.
AB  - OBJECTIVES: The aim of this study was to evaluate feasibility and safety of
      laparoscopic surgery for rectosigmoid cancer and rectal cancer. MATERIAL AND
      METHOD: Twenty four patients who underwent laparoscopic surgery for rectosigmoid
      cancer or rectal cancer were retrospectively evaluated. Results were compared
      with those of 25 patients who had open surgery at the same period. The procedures
      of both groups were anterior resection, low anterior resection, coloanal
      anastomosis, abdominoperineal resection and subtotal colectomy. RESULTS: The mean
      operative time was significantly increased in the laparoscopic group. However,
      this group showed faster recovery of bowel function. There were no differences in
      the distal margin and yield of harvested lymph nodes of resected specimens.
      Although anastomotic leakage was comparable between 2 groups, surgical wound
      infection was significantly higher in open surgery group. CONCLUSION:
      Laparoscopic surgery for rectosigmoid cancer and rectal cancer is feasible and
      can be performed safely with comparable oncological clearance.

PMID- 16623005
TI  - The new laparoscopic proctocolectomy training (in soft cadaver).
AB  - OBJECTIVES: The purpose of the present study was to evaluate the quality of
      preservation (tissue plane, named vessels identification, consistency of colon
      and rectum), quality of performing procedures, difficulties and problems and
      finally the satisfaction of surgeons in laparoscopic proctocolectomy in soft
      cadaver. SETTING: Colorectal Division, Department of Surgery and Surgical
      Training Center Department of Anatomy, Faculty of Medicine, Chulalongkorn
      University. DESIGN: Prospective descriptive study MATERIAL AND METHOD: 10 soft
      cadavers were scheduled for laparoscopic proctocolectomy. The procedures (colon
      rectum mobilization and named vessels identification) were performed by 14
      experienced surgeons (8 colorectal surgeons) and assisted by surgical residents.
      The quality of preservation, successfulness and the satisfaction in performing
      the procedures were recorded using questionnaires for evaluation. RESULTS: The
      preservation was very good in every aspect especially tissue plane between colon,
      mesocolon and retroperitoneum which was clearly dissected, same asfasciapropria
      of rectum. The named vessels and the tissue consistency were very well preserved
      and tolerated to laparoscopic equipment handling. The surgeons were satisfied
      with the tissue handling and dissections. There were two difficulties, the first
      was air leakage but simply corrected with purse string suture and the second was
      unflavored smell which was not concerned. Laparoscopic proctocolectomy could be
      completely performed in soft cadaver. CONCLUSION: Laparoscopic proctocolectomy
      could be performed in soft cadavers with great satisfaction. Repeated practice is
      possible, so the surgeons can gain their experiences outside the operating
      theatre. This success may shorten the learning curve and may be the new era in
      cadaver-based training.

PMID- 16623006
TI  - Bilateral scrotal flaps: a skin restoration for penile paraffinoma.
AB  - Foreign body injection into the penile shaft, in the mistaken belief that it
      could increase the size, is not uncommon among Thai males. Paraffin, oil, and
      other materials had been injected into the penile skin and predictably followed
      by a lot of complications. Foreign body granuloma, disfigurement, chronic and
      unhealed ulcer, painful erection, and the inability to achieve sexual activities
      are those following complications. In the severe cases, even though the complete
      resection of the skin and all of the infiltrated tissue was meticulously
      performed, some foreign bodies had to be left since they had incorporated into
      either the corpus cavernosum or corpus spongiosum. Durable resurfacing skin can't
      be perfectly achieved by skin grafting in these situations. Between 1996 and
      2002, 31 patients with penile paraffinoma have been treated using bilateral
      scrotal flaps. Both functional and cosmetic goals without any major complications
      were achieved in all of the patients.

PMID- 16623007
TI  - Results of the 136 consecutive minimally invasive total knee arthroplasties.
AB  - The authors evaluated results of 136 consecutive minimally invasive total knee
      arthroplasties (MIS TKAs). The first 22 knees, performed with strict patient
      selection criteria, were determined as a learning experience. According to
      results of the next 114 knees, the average wound length was 9.2 centimeters and
      the average blood loss was 470 milliliters. At a mean follow-up of 14 months, the
      mean Knee Society score improved from 37.5 to 96 points with 96.3% of excellent
      results. Sixty-five knees, group A, had within 10 degrees of varus and 49 knees,
      group B, had more deformity. Clinical results of both groups were not
      statistically different in terms of operative time, blood loss, pain score,
      postoperative knee flexion at 2 weeks and 6 months and postoperative day of
      walking. However, the ability to straighten the knee was significantly delayed in
      knees with more deformity (group B). After gaining learning curve, surgeons could
      extend performing MIS TKA in patients with more knee deformity.

PMID- 16623008
TI  - Effects of shoe lift on weight bearing in stroke patients.
AB  - OBJECTIVES: To determine the effect of shoe lift, cueing and cueing with shoe
      lift on weight bearing in paretic leg of stroke hemiparetic patients and compare
      the effect between each condition. DESIGN: Cross-sectional experimental study.
      SETTING: Department of Rehabilitation Medicine and Department of Ear Nose and
      Throat, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn
      University. SUBJECT: Ten hemiparetic patients as a result of unilateral stroke.
      MATERIAL AND METHOD: Weight symmetry of each patient was measured by
      posturography during quiet stance and in conditions of compelled weight shift.
      Each patient was started with quiet standing, standing with shoe lift under the
      sound leg; cueing and cueing with shoe lift under the sound leg respectively.
      Weight symmetry scores were recorded for comparing the weight distribution
      between each foot. RESULTS: There were 10 hemiparetic patients. Seven were male.
      The average age was 53.4 +/- 8.45 years. There were 5 right hemiparesis and 5
      left hemiparesis. The average onset was 12.3 +/- 15.73 months. In the right
      hemiparetic patients, weight bearing in the paretic leg was significantly
      improved when cueing with shoe lift compared with quiet standing and with shoe
      lift (Backward p = 0.012, Forward p = 0.011 and Backward p = 0.001, Forward p =
      0.036 respectively). In the left hemiparetic patients, weight bearing in the
      paretic leg was significantly improved when cueing compared with quiet standing
      (Backward p = 0.046), and when using the shoe lift (Backward p = 0.016). Cueing
      with shoe lift could significantly improve weight bearing in the paretic leg when
      compared with shoe lift alone (Backward p = 0.015). Shoe lift alone could improve
      weight bearing in the paretic leg of the right and left hemiparetic patients but
      was not statistically significant (p > 0.05). CONCLUSION: Cueing with shoe lift
      under the sound leg can significantly improve weight bearing of the paretic leg
      of the right and left stroke hemiparetic patients.

PMID- 16623009
TI  - Reliability of foot caliper.
AB  - OBJECTIVES: To determine the reliability of foot caliper DESIGN: Descriptive
      study. SETTING: Rehabilitation Medicine Outpatient Department, King Chulalongkorn
      Memorial Hospital. SUBJECT: Fifteen volunteers were recruited from Rehabilitation
      residents and health care professionals of Department of Rehabilitation Medicine,
      King Chulalongkorn Memorial Hospital. MATERIAL AND METHOD: The authors created 3
      sets of simple Foot Caliper and measured foot dimension including foot width,
      foot length and toe depth while subjects stood with equal weight bearing to both
      feet. The authors set 3 examiners to measure foot dimension by the same method.
      To determine reliability of 3 sets of foot caliper, one examiner was assigned to
      measure foot dimension of 30 feet with all calipers. To determine the reliability
      of examiners, all examiners measured foot dimension of the same 30 feet. All
      parameters were recorded in millimeters. The data was analyzed and presented as
      intraclass correlation coefficients (ICC) with 95% CI. RESULTS: There were
      fifteen volunteers (8 men and 7 women). The average age was 28.6 +/- 4.11 years
      (range 22-39). Average foot width,length and great toe depth (millimeters) were
      9.64 +/- 0.63, 24.17 +/- 1.10 and 1.91 +/- 0.24 respectively. For reliability
      analysis of 3 sets off foot caliper, the intraclass correlation coefficients
      (ICC) with 95% CI were 0.985 (0.972-0.992), 0.996 (0.992-0.998) and 0.982 (0.968
      991) for foot width, length and great toe depth, respectively. For Inter-examiner
      reliability, intraclass correlation coefficients (ICC) were 0.941 (0.864-0.969),
      0.850 (0.46-0.920) and 0.834 (0.721-0.910) for foot width, length and great toe
      depth, respectively. These results showed high agreement of data. CONCLUSION:
      These simple foot calipers have high reliability forf oot measurement. These
      devices are appropriate for clinical use.

PMID- 16623010
TI  - Star excursion balance training: effects on ankle functional stability after
      ankle sprain.
AB  - OBJECTIVES: To study the effects of Star Excursion Balance training on functional
      stability of athletes with ankle sprain. MATERIAL AND METHOD: Thirty-two male
      athletes with grade 2 ankle sprain, aged 15-22 years old were enrolled. They were
      random sampling into training group (n=15) and control group (n=17). All received
      conventional physical therapy program for 4 weeks. The training group also
      underwent the Star Excursion Balance training 3 days per week for 4 weeks. Single
      leg stance time (SLST) was assessed at pre- and post-training. Re-injuries were
      recorded during 3 months follow-up. RESULTS: After the program, subjects from
      both groups demonstrated significant improvement in SLST The training group
      gained SLST of the injured sides 2 times more than the control group (p = 0.002
      tested with eyes closed, p = 0. 007 tested with eyes open), and also improved the
      SLST during eyes closed of the normal sides (p = 0.015). Re-injuries were found
      in 1/15 of the training group and 2/17 of the control group. CONCLUSION: Star
      Excursion Balance training is more effective than the conventional therapy
      program in improving functional stability of the sprained ankle.

PMID- 16623011
TI  - Pattern of angular change of the anterior cruciate ligament across the range of
      knee flexion and the related anatomical dimensions.
AB  - Improper femoral and/or tibial tunnel placements are major causes of failure in
      anterior cruciate ligament (ACL) reconstruction. The 52 embalmed cadaveric knees
      were measured the dimensions of the surgical related structures using vernier
      caliper and goniometer. The intercondylar notch width was 17.4 +/- 2.3 mm and
      slope of the roof was 31.3 +/- 3.4 degrees. The average length of ACL was 21.6 +/
      2.5 mm. The relation of tibial attachment was 47.98% of the width of the lateral
      tibial plateau and 49.8% anteriorly, when it was measured through ACL attachment.
      Angle of ACL in sagittal plane was decreased during knee flexion. On the
      contrary, angle of ACL in coronal plane was increased during knee flexion.
      According to this study), The expected femoral tunnel at 10.00 am to 10.30 am
      could be performed by arthroscopic transtibial technique using the 48% of tibial
      width anteriorly for intraartricular tibial-tunnel drill-guide placement and
      aiming for sagittal and coronal plane of 52.0+/-4.6 / 20.9+/-3.9, 46.2+/-5.1 /
      26.8+/-4.6 degrees, and 41.6+/-5.1 / 32.0+/-4.3 degrees while knee flexion degree
      were as 60, 90, and 120 degrees, respectively.

PMID- 16623012
TI  - The prevalence and risk factors of osteoporosis in Thai renal-transplant
      patients.
AB  - OBJECTIVES: To determine the prevalence and risk factors of osteoporosis after
      renal transplantation in Thai patients. MATERIAL AND METHOD: A single-center
      cross-sectional study of bone mineral density was conducted in 102 Thai renal
      allograft recipients. Correlations were made between the clinical parameters and
      the occurrences of osteoporosis. RESULTS: The prevalence of osteoporosis was
      24.5%, 9.8% and 26.4% at lumbar vertebrae, hip region, and any sites,
      respectively. Binary logistic regression analysis revealed that cumulative dosage
      of steroids was significantly correlated with osteoporosis of the lumbar spine (p
      = 0.023, adjusted OR = 1.005), while body mass index (p = 0.005, adjusted OR =
      0.738) and age (p = 0.052, adjusted OR = 1.077) were correlated with osteoporosis
      of the hip region. CONCLUSION: Osteoporosis is common in Thai renal allograft
      recipients, particularly of the lumbar vertebrae. Cumulative dosage of steroids
      is the most important risk factor of low BMD of the lumbar vertebrae.

PMID- 16623013
TI  - Prevalence of anatomic variation demonstrated on screening sinus computed
      tomography and clinical correlation.
AB  - Screening sinus computed tomography (SCCT) of 133 patients performed from March
      2003 to February 2004, were retrospectively reviewed, concerning anatomic
      variation at ostiomeatal unit (OMU) and nasal septal deviation. Six patterns of
      inflammatory sinus disease were designated: maxillary infundibulum, nasofrontal
      duct, OMU, sphenoethmoidal recess, polyposis and sporadic. The most common
      anatomic variation was concha bullosa (14.3%), followed by Haller cell (9.4%),
      large Agger nasi cell (7.9%) and paradoxical middle turbinate (5.3%). Nasal
      septal deviation was presented in 75 patients (56.4%). Inflammatory sinus disease
      was presented in 181 lateral nasal walls (68%) and maxillary infundibular pattern
      was the most common (33.1%). There was significant correlation between large
      Agger nasi cell and nasofrontal duct pattern (p < 0.05). The remaining anatomic
      variations and nasal septal deviation had no significant correlation to the
      inflammatory sinus disease. Overall, the anatomic variation which can compromise
      the mucociliary drainage was frequently observed, however, only the large Agger
      nasi cell had significant correlation to the inflammatory sinus disease.

PMID- 16623014
TI  - Capacity of the unused bladder in end stage renal disease.
AB  - OBJECTIVES: To evaluate the bladder capacity in patients diagnosed with end stage
      renal disease (ESRD). MATERIAL AND METHOD: A six-month prospective study was
      conducted at the outpatient X-ray unit, Department of Radiology, King
      Chulalongkorn Memorial Hospital from July 2002 to January 2003. Datas from adult
      patients sent to the unit for voiding cystourethrography (VCUG) were collected.
      Bladder capacity was obtained by calculating the amount of contrast material
      introduced into the urinary bladder in each VCUG. The urinary bladder was assumed
      to be at the maximum capacity when the patient had a strong desire to void during
      contrast instillation. Patients with voiding dysfunction or neurogenic bladder
      were excluded from the present study. RESULTS: There were 11 patients with ESRD
      (male=7, female=4, mean age=41 years) and 7 patients without ESRD (male=1,
      female=6, mean age=41 years). The maximum bladder capacity was 400 ml for the
      ESRD patients and 500 ml for the non-ESRD patients. The smallest bladder capacity
      was 100 ml for the ESRD patients and 250 ml for the non-ESRD patients. The mean
      bladder capacity was 254.5 ml (+/-SD) for the patients with ESRD and was 364.28
      ml for the patients without ESRD. The P-value was 0.043. In conclusion, the mean
      bladder capcity of the patients with ESRD was statistically smaller than that of
      patients without ESRD.

PMID- 16623015
TI  - Risk factors of female urinary incontinence and overactive bladder in Thai
      postmenopausal women.
AB  - OBJECTIVES: To assess the risk factors of stress incontinence (SUI), Urge
      incontinence (UI), mixed type incontinence (MUI) and overactive bladder (OAB) in
      Thai postmenopausal women. MATERIAL AND METHOD: A total of 360 Thai post
      menopausal women (60 had SUI, 60 had UI, 60 had MUI, 60 had OAB, and 120 were
      controls). All women attended the gynecologic clinic at King Chulalongkorn
      Memorial Hospital during January-June 2004. All cases and controls were given
      questionaires on the risk factors of age, body mass index (BMI), years since
      menopause, alcohol intake, routes and number of deliveries, history of chronic
      cough and constipation, and current hormonal therapy use. The multivariate
      logistic model was used to identified the independent risk factors and female
      urinary incontinence and OAB. RESULTS: In multivariate analysis, no factor was
      associated in UI or OAB group. In the SUI and MUI group, only the history of
      chronic cough [in SUI gr: OR 1.6 (1.1-2.3) in MUI gr: OR 3.5 (1.2-10.4)] and
      history of chronic functional constipation [in SUI group or 4.7 (1.5-14.7), in
      MUI or 3.0 (1.1-7.9)]. CONCLUSION: Chronic cough and chronic functional
      constipation were the associated risk factors in stress and mixed type
      incontinence in Thai postmenopausal women.

PMID- 16623016
TI  - Malignant ovarian germ cell tumor in King Chulalongkorn Memorial Hospital.
AB  - OBJECTIVES: To determine the frequency, characteristics, treatment and outcome of
      patients with malignant ovarian germ cell tumor (MOGCT) in King Chulalongkorn
      Memorial Hospital during the period January 1992 - December 2000. STUDY DESIGN:
      Retrospective descriptive study MATERIAL AND METHOD: All patients with malignant
      ovarian germ cell tumor in King Chulalongkorn Memorial Hospital during the period
      January 1992 - December 2000 were analyzed by the characteristics of patients,
      treatment and outcome. RESULTS: Sixty-six patients with MOGCT were demonstrated
      in that period with a mean age of 22.6 years old. Most of the patients were
      nulliparous and premenopausal status. Primary surgery was done in all patients.
      Forty-two patients (63.6%) received conservative surgery. Eight patients received
      no adjuvant treatment after surgery due to stage 1A dysgerminoma and immature
      teratoma stage I grade I. Fifty-six patients received chemotherapy for adjuvant
      treatment. VAC regimen was given in 27 cases (40.9%) and PVB regimen was given in
      25 cases (37.9%). Salvage therapy in the patients with persistent and recurrent
      disease was treated in 9 patients, who received a platinum-base of regimen. Two
      year survival was 88% with the median time to follow up 24 months. Overall five
      year survival in the present study was 85%. CONCLUSION: MOGCT in King
      Chulalongkorn Memorial Hospital had clinical characteristics similar to other
      studies in malignant ovarian germ cell tumor Treatment by VAC regimen still has
      benefit in selected group.

PMID- 16623017
TI  - Clinical characteristics of inflammatory bowel disease in Thailand: a 16 years
      review.
AB  - OBJECTIVE: Inflammatory bowel disease is an uncommon gastrointestinal problem in
      Asia. Recently, there have been many reports from Japan and India demonstrating a
      higher incidence of this disease entity in this region. To date, there has been
      only one report from Thailand regarding clinical manifestation of ulcerative
      colitis. However, information regarding Crohn 's disease has never been
      demonstrated. MATERIAL AND METHOD: The authors retrospectively reviewed clinical
      data on both ulcerative colitis (UC) and Crohn's disease (CD) during a 16 year
      period from the medical records of King Chulalongkorn Memorial Hospital, one of
      the main referral centers in Thailand. RESULTS: There were 55 patients diagnosed
      as inflammatory bowel disease. Of these, 45 were diagnosed as UC and the rest
      were CD. Mean age of UC and CD patients was 32 and 40.5 years respectively. The
      authors did not find any significant relationship between smoking and colonic
      cancer in these patients. The main presentations of UC patients were mucous
      bloody diarrhea and watery diarrhea whereas watery diarrhea, fever and weight
      loss were the main presentations of patients with CD. There were fistulas in 2 CD
      patients. In addition, oral ulcer and panuveitis were diagnosed in 2 different CD
      patients. One UC patient had PSC (primary sclerosing cholangitis) and another had
      pyoderma gangrenosum. The majority of UCpresented as pancolitis (46.7%) while
      ileocolic involvement was more common in CD (60%). CONCLUSION: In Thailand, UC is
      more common than CD whereas disease involvement is more localized to ileocolic
      region in CD than UC. Similar to Western countries, both UC and CD are presented
      at relatively young age.

PMID- 16623018
TI  - Effect of diabetes drug counseling by pharmacist, diabetic disease booklet and
      special medication containers on glycemic control of type 2 diabetes mellitus: a
      randomized controlled trial.
AB  - BACKGROUND: type 2 diabetes mellitus continues to increase in prevalence
      worldwide. Many factors have been cited as contributing to compliance, such as
      family and social support, education, number of tablets per dose, frequency of
      administration and health care provider communication. Toward these goals, the
      present study was developed to measure the effect offactors on glycemic control
      such as diabetes education by pharmacists, a diabetes disease booklet and special
      medication containers. MATERIAL AND METHOD: A total of 360 volunteers with type 2
      DM patients were recruited, participants were simple randomized to control 180
      and intervention 180 patients. Which intervention categorized to 4 groups; all
      intervention groups received diabetes drug counseling by a pharmacist, one group
      received plus a diabetes booklet, one received plus special medical containers
      and the last group received all of them. The interventions were done at the 1st
      time of visit. Both the control and intervention groups were monitored for
      fasting plasma glucose and HbA1c at 0, 3, 6 months and glycemic level in both
      groups was compared. RESULTS: After 3 months, mean fasting plasma glucose and
      HbA1c decreased wiih the intervention group vs. control group (152.36 +/- 39.73
      to 131.52 +/- 35.22 mg%) and (150.16 +/- 41.78 to 153.98 +/- 47.95 mg%)
      respectively; (p < 0.001). HbA1c level 8.16 +/- 1.44 to 7.72 +/- 1.26 vs 8.01 +/-
      1.51 to 8.38 +/- 1.46 respectively; (p < 0.001). After 6 months, mean fasting
      plasma glucose and HbA1c decreased with the intervention group vs. control group
      (152.36 +/- 39.73 to 145.20 +/- 46.07 mg%) and (150.16 +/- 41.78 to 159.16 +/-
      54.90 mg%) respectively; (p < 0.013). HbA1c level 8.16 +/- 1.44 to 7.91 +/- 1.27
      vs. 8.01 +/- 1.51 to 8.80 +/- 1.36 respectively; (p < 0.001). The most favorable
      glycemic outcome was the group that received all of the interventions; mean FPG
      was reduced from 147.46 +/- 36.07 to 125.38 +/- 31.12 mg% (p < 0.000) in 1nd
      visit (3 months later) and still reducing effect on the 2nd visit (6 month later)
      mean FPG from 147.46 +/- 36.07 to 130.21 +/- 33.96 mg% (p < 0.016) also the same
      way in HbA 1c level. The group that received only drug counseling by pharmacist
      had no significant reduction in FPG and HbA1c. (p > 0.05). CONCLUSION: Drug
      counseling by a pharmacist has little beneficial effect on diabetes management
      outcome compared to the diabetes booklet and special drug container. To improve
      glycemic control of type 2 DM is to integrate self-management in daily life, wide
      a variety of education, drug taken behavior and health care provider available
      communication produce improvement in patient management and is somewhat better
      when used in combination.

PMID- 16623019
TI  - The use of electroconvulsive therapy and the length of stay of psychiatric
      inpatients at King Chulalongkorn Memorial Hospital, Thai Red Cross Society.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) is the effective treatment in
      psychiatric patients. However, the controversies about the risk and benefit limit
      the use of this procedure. Some efficacies of ECT may be interesting to use in
      hospitalized patients such as rapid onset, risk reduction but it may increase the
      length of stay (LOS) in previous study. OBJECTIVES: To study the use of ECT in
      hospitalized psychiatric patients in the aspect of indication , diagnosis and the
      length of stay. MATERIAL AND METHOD: From August to September 2004, all 51 cases
      of psychiatric inpatient medical records were studied. The top five of diagnosis
      were schizophrenia (49%), bipolar disorder (23.5%), acute psychosis (7.8%),
      depressive disorder (5.9%) and dementia (5.9%). ECT was performed in 22 cases
      (43.1%). RESULTS: The average length of stay was 21.5 +/- 14.5 days. The mean LOS
      of the ECT group 25.9 +/- 15.8 days was not quite longer compared with 17.8 +/-
      12.7 days of the Non ECT group comparison between the ECT group (64%) and the non
      ECT group (36%) of schizophrenia, the LOS of each group was 27.3 +/- 16.7 and
      16.9 +/- 8.8 days which was also not significant. LOS of ECT of the bipolar group
      (20%) and the non ECT bipolar group (80%) was 10.5 +/- 4.9 and 23.0 +/- 18.3 days
      which was not statistically significant (p = 0.39). There were 3 major
      indications for ECT such as a severe violence case, suicidal case, refractory
      case with the mean LOS of 19.9 +/- 10.9, 17.5 +/- 12.8, 43.3 +/- 21.2 and 31.7 +/
      8.3 days subsequently. The patients who had the refractory indication had a
      longer length of stay than other indications. CONCLUSION: Overall average length
      of stay was not longer in the ECT group. The ECT group had a longer length of
      stay than the non ECT group in the refractory treatment case only. ECT can be
      used in a psychiatric ward with the efficacy of its indication without prolonged
      length of stay.

PMID- 16623020
TI  - Factors associated with compliance among tuberculosis patients in Thailand.
AB  - BACKGROUND: Tuberculosis (TB) is a major health problem in developing countries.
      There are so many factors which influence the cure rate and one of them is
      compliance. However in developing countries like Thailand, there is little
      information about the factors that can predict the compliance within TB patients.
      OBJECTIVES: To study the level of compliance and associated factors among
      tuberculosis patients in Thailand. DESIGN: A cross-sectional descriptive study.
      SETTING: Three levels of health care facilities in the 4 regions of Thailand
      (Zonal TB Centers, Provincial Hospitals and District Hospitals), excluding
      Bangkok. PARTICIPANTS: A total of 487 adult newly diagnosed TB patients with
      positive sputum smear at the study location and they were interviewed by trained
      health personnel with structured questionnaires. MAIN OUTCOME MEASURES: Level of
      compliance classified into excellent (punctuality), good (missing < or =2
      consecutive weeks) and poor (missing >2 consecutive weeks). The socio-economic
      variables were studied as the independent variables. RESULTS: About 70% (342 out
      of 487)of the TB patients were males. Mean (SD) of age was 47.2 (16.65) years and
      ranged from 15 to 84 years. The excellent compliance rate of the TB patients was
      65.7% (95% CI: 61.5-69.6%) while good and poor compliance were 22.8% and 11.5%,
      respectively. Using Chi-square test of association, the finding showed that the
      type of treatment (DOT and SS), gender, working, experience of contacting TB
      patient, perception in health status, attitude, knowledge and social support were
      significantly associated with the compliance (p < .05). Binary logistic
      regression (Excellent vs. Good and Poor) were used to adjust the confounding
      factors. Females were more likely to have excellent compliance than males
      (adjusted OR = 1.87, 95% CI: 1.17-2.99, p = .009). Patients having perception of
      fair health status was 2.26 times more to have excellent compliance (95% CI: 1.45
      3.53, p < .001). CONCLUSION: Compliance is one of the potential factors to
      increase the cure rate in TB patients. Finding the significant factors will pave
      the way to improve the effective treatment of tuberculosis.

PMID- 16623021
TI  - Pharmacokinetics of sirolimus in Thai healthy volunteers.
AB  - Sirolimus, a novel immunosuppressive drug, has been used in kidney transplant
      recipients to minimize calcineurine inhibitor (CNI) and steroid toxicities.
      Likewise CNI, Sirolimus's pharmacokinetics have both inter and intra-individual
      pharmacokinetic variations. Due to ethnic differences, the recommended oral
      loading dose of 6 mg and oral maintenance dose of 2 mg per day for Caucasian
      patients and oral loading dose of 10 mg and oral maintenance dose of 5 mg per day
      for African-American patients may not be appropriate for Asian recipients. We,
      therefore conducted the pharmacokinetic study of sirolimus in Thai population,
      aimed to delineate the appropriate sirolimus dose for further clinical use. The
      study was performed in 12 healthy Thai volunteers. After an over night fasting, a
      single oral dose of 6 mg sirolimus was given. The complete pharmacokinetic study
      was done by UVhigh performance liquid chromatography (HPLC-UV) to measure the
      whole blood sirolimus level at 0.5 hour after the dose (C0.5) and then C1, C1.5,
      C2, C2.5, C3, C4, C6, C8, C12, and C24 hours. A complete area under the
      concentration time curve from 0-24 hours (AUC(0-24 hr)) was calculated by using
      the trapezoidal rule. The mean (+/- SD) time to maximal concentration (Tmax) was
      1.45 +/- 0.5 hr (range 1-3 hrs). The maximal (Cm) and minimal plasma
      concentration (Ctroug) for sirolimus were 25.3 +/- 6.1 ng/ml (range 18.10 - 40
      ng/ml) and 4.47 +/- 0.57 ng/ml (range 2.90 - 7.20) ng/ml respectively. The AUC(0
      24 hr) were 187.9 +/- 48.2 ng * hr/ml (range 151.3 - 294.8 ng * hr/ml). Sirolimus
      level at 4 hr post-dose had the best of correlation with AUC(0-24 hr) (Pearson
      correlation = 0.76, p < 0.007). One volunteer had a very high sirolimus level.
      This subject's pharmacokinetic data showed AUC(0-24 hr) of 256 ng * hr/ml and
      Cmax of 40 ng/ml. In conclusion, the oral loading dose of 6 mg of sirolimus in
      Thai volunteers did not achieve the recommended therapeutic level (5-10 ng/ml) in
      most subjects. There are differences in pharmacokinetics of sirolimus between
      Thais and Caucasians.

PMID- 16623022
TI  - Resolution of eosinophilia after treatment of cutaneous gnathostomiasis.
AB  - The present study was to investigate the dynamics of eosinophil in peripheral
      blood of patients with cutaneous gnathostomiasis before and after worm removal.
      The total of 28 proven cases of cutaneous gnathostomiasis treated by albendazole
      were included in the present study. The absolute eosinophil count (AEC) was
      higher than 500/ul during infestation in almost all the patients, the positive
      rate was 89%, and significantly decreased to normal level after receiving
      albendazole and worm removal within 3 months in 96%. In conclusion, an increas of
      AEC is another important hallmarks of cutaneous gnathostomiasis and this
      parameter could be the earlier indicator for responsiveness to treatment.

PMID- 16623023
TI  - A comparison of the efficacy between two itraconazole generic products and the
      innovative itraconazole in the treatment of tinea pedis.
AB  - BACKGROUND: Treatment of tinea pedis with conventional oral antifungal agents
      produces poor response rates. Itraconazole is a broad-spectrum, orally active
      antifungal agent with pronounced antimycotic activity. However treatment cost of
      itraconazole is problematical in developing countries. OBJECTIVES: To study the
      efficacy of the 1-pulse dosing regimen of two generic products of itraconazole
      (Itracon and Itra) in comparison with the innovative product (Sporal) for the
      treatment of tinea pedis. MATERIAL AND METHOD: The study was a double-blind
      randomized controlled trial. One hundred and thirty-three patients with tinea
      pedis were treated with Itracon, Itra or Sporal 200 mg twice daily for 1 week.
      Clinical and mycological examinations were performed at baseline and at the
      follow-up visits (taking place at 1, 2, 4 and 12 weeks after the medication
      administration). RESULTS: Fifty-four, sixty-one and eighteen patients were
      randomized to Sporal, Itracon and Itra treatment group respectively. Mycological
      cure rate and clinical response rates were not significantly different among the
      three groups. Moreover there were also no statistically significant differences
      with regard to relapse rate. During treatment, no serious adverse events were
      recorded in any groups. CONCLUSION: The present study demonstrated that the
      efficacy of the original and generic itraconazole is not significantly different
      in the treatment of tinea pedis by the pulse regimen.

PMID- 16623024
TI  - Efficacy of aloe vera cream in prevention and treatment of sunburn and suntan.
AB  - The efficacy of aloe vera cream in prevention of burn and tan from ultraviolet
      were studied in 20 volunteers. The minimal erythema dose of 20 volunteers were
      tested. The mean MED was 40-60 mj. The well preserved containing 70% of aloe vera
      cream. The aloe vera cream was applied randomized double blind technique on the
      test sites 30 minutes before, immediately after, or both before and after then
      the serial ultraviolet UVB 40,50,60,70,80 mj were radiated. MED reading at 24
      hour for sunburn evaluation. Erythema and pigmentation were evaluated by visual
      grading 1-4 score. The aloe vera cream was continuing applied at the test sites
      twice daily for the the next three weeks. The results showed that the aloe vera
      cream has no sunburn or suntan protection and no efficacy in sunburn treatment
      when compared to placebo. The aloe vera cream has no bleaching effect too.

PMID- 16623025
TI  - Result of standard patch test in patients suspected of having allergic contact
      dermatitis.
AB  - Contact dermatitis is a common skin disease. Disease was diagnosed by a history
      of contact substance together with geographic distribution of lesion. Up till
      now, standard patch test is one of the most reliable test to identify and confirm
      causative agent of allergic contact dermatitis. To determine the rate of positive
      standard patch test and to identify the common allergen of contact dermatitis in
      Thailand, we performed the standard patch test in 129 patients, suspected having
      allergic contact dermatitis at Department of Dermatology, King Chulalongkorn
      Memorial Hospital, Thailand from June 1, 2003 to September 1, 2004. The rate of
      positive standard patch test is 59.7% (n = 77/129). The most 3 common positive
      allergens were nickel sulfate (18.60%), cobalt chloride (17.05%) and fragrance
      mix (14.73%), respectively. The chance of positive standard patch test
      significantly correlated with sex (woman), initial diagnosis as contact
      dermatitis and history of house-worker (p = 0.017, p = 0.005 and p = 0.023,
      respectively). Whereas, there were no significant correlation between the chance
      of positive standard patch test and age of patient, location of lesion, history
      of recurrence, history of atopy, history of drug and food allergy. In addition,
      history of metal allergy significantly correlated with the chance of positive
      nickel sulfate or cobalt chloride in standard patch test (p = 0.017). In
      conclusion, this study demonstrated the prevalence of causative allergen of
      contact dermatitis in Thai patients using that standard patch test. Moreover, our
      data shown that the chance positive standard patch test was greater in patient,
      who were women or initial diagnosed as contact dermatitis or had history of
      houseworker or history of metal allergy.

PMID- 16623026
TI  - Intravenous iron administration during the maintenance period in erythropoietin
      treated hemodialysis patients: a simple and effective method.
AB  - OBJECTIVES: To determine the interval of intravenous iron administration during
      maintenance iron therapy in erythropoietin-treated hemodialysis patients.
      MATERIAL AND METHOD: The method of maintenance intravenous iron therapy has been
      studied in 20 stable erythropoietin-treated hemodialysis patients who have iron
      deficiency anemia diagnosed by transferring saturation (TSAT) below 20%. RESULTS:
      After receiving 1000 mg of intravenous iron as the first loading dose, the TSAT
      was increased from 16.4 +/- 0.5 to 29.3 +/- 2.6% (p < 0.05). After 155.6 +/- 7.3
      days, such values was reduced to 16.3 +/- 1.4% (p < 0.05). The second loading
      dose was administered and could raise the TSAT to 33.7 +/- 3.9% (p < 0.05). The
      patients, then, received 100 mg of intravenous iron for every 15.6 +/- 2.9 days,
      one-tenth of the duration between the two loading doses. The values of TSAT at 1,
      2, 3, 4, 5 and 6 months after the second loading dose were 38.5 +/- 2.4, 37.1 +/-
      0.2, 34.2 +/- 3.6, 34.1 +/- 3.3, 35.3 +/- 4.1, and 36.5 +/- 3.1% (NS).
      CONCLUSION: As such, in erythropoietin-treated hemodialysis patients, after
      loading with 1000 mg, prescription of 100 mg of intravenous iron for every 2
      weeks could maintain the TSAT levels above 20%.

PMID- 16623027
TI  - Minimally invasive surgery training in soft cadaver (MIST-SC).
AB  - OBJECTIVES: The purpose of this study was to evaluate the surgical anatomy,
      tissue plane, organ consistency of soft cadaver and the possibility of minimally
      invasive surgery training in soft cadaver. SETTING: Surgical Training Center.
      Department of Anatomy and Department of Surgery Faculty of Medicine,
      Chulalongkorn University. DESIGN: Prospective descriptive study. MATERIAL AND
      METHOD: 2 soft cadavers were scheduled for fully laparoscopic surgery in upper
      gastrointestinal, colorectal, hepatopancreatobiliary and solid organs surgery.
      All the procedures were performed by the experienced surgical staffs and assisted
      by surgical staffs and/or surgical residents. The surgical anatomy, tissue plane,
      organ consistency and the satisfactory in performing the procedures were recorded
      for evaluation. RESULTS: The surgical anatomy, the tissue consistency the
      anatomical plane were very well preserved with mean score of 4.72 +/- 0.45. All
      the surgeons were satisfied with the findings, the mean score was 4.97 +/- 0.18.
      All the plan procedures were completely performed with great satisfactory
      results. CONCLUSION: The Minimally Invasive Surgery Training in Soft Cadaver
      (MIST-SC) was feasible with great satisfactory. This successful integration of
      basic and advanced laparoscopic procedures into the soft cadaver setting would be
      the next step in evolution of MIS training.

PMID- 16623028
TI  - Comorbidity of alcohol dependence in suicidal depressed patients.
AB  - OBJECTIVES: To study the characteristics of suicidal attempt patients who had
      depressive symptoms and to assess the comorbidity of alcohol problems in those
      patients. MATERIAL AND METHOD: One hundred and ten patients aged over 18 years
      who received psychiatric consultation for suicidal attempt and had clinical of
      depression without psychotic features were evaluated for clinical symptoms,
      details of self-harming, history of alcohol use disorder and family history of
      substance use or suicide. The severity of depression was measured objectively
      with Hamilton Depression Rating Scale. RESULTS: Most cases of suicidal depressed
      patients were female (81 cases). The mean score of severity of depression from
      HAM-D was 16.2 (SD 3.52) that indicated moderate degree. The method employed for
      suicidal attempt was ingestion of drug or chemical agents. About 33% of subjects
      had comorbid alcohol use disorder and in this group 12.7% was diagnosed as
      alcohol dependence. Factors associated with suicidal depressed patients who had
      comorbid alcohol use disorder were male, aged above 30 years and lower education
      and additionally, in those with alcohol dependence were associated with stressor
      about financial problems and less likely to attempt suicide by acetaminophen
      overdose or be precipitated by relationship problem. CONCLUSION: Comorbid alcohol
      use disorder is common among depressed patients who attempted suicide. More
      concern about recognition of these comorbidities particularly in those with
      associated factors and giving appropriate treatment for the comorbidity may be
      helpful for prevention of suicide.

PMID- 16623029
TI  - Reducing radiation dose to pelvic small bowel in cervical cancer patients treated
      with Ir-192 intracavitary brachytherapy by using urinary bladder distension.
AB  - OBJECTIVES: Several techniques and devices have been used in an attempt to
      minimize radiation dose to gastrointestinal tract while giving pelvic radiation.
      We evaluated the effect of urinary bladder distension to displace pelvic small
      bowel out of intracavitary brachytherapy field to minimize radiation dose to
      small bowel in cervical cancer patients. MATERIAL AND METHOD: Eleven cervical
      cancer patients who received Ir-192 intracavitary brachytherapy with tandem and
      transverse ovoids were included in this study. Oral contrast material was used to
      visualize pelvic small bowel. Urinary bladder was distended by injection 125-200
      ml. normal saline solution. Pelvic radiograph, anteroposterior and lateral view,
      was performed before and after bladder distention for brachytherapy treatment
      planning and comparing radiation dose at small bowel. RESULTS: The average
      maximum radiation dose at small bowel before and after bladder distension were
      3123 cGy and 1998 cGy respectively. The summation of small bowel dose was reduced
      54.17% (p = 0.002). CONCLUSION: Urinary bladder distension could effectively
      displace pelvic small bowel and reduce the radiation dose to small bowel from Ir
      192 intracavitary brachytherapy in cervical cancer patients.

PMID- 16623030
TI  - Quality of life after successful epilepsy surgery: evaluation by occupational
      achievement and income acquisition.
AB  - OBJECTIVES: A comprehensive epilepsy surgery program has been developed at
      Chulalongkorn University Hospital, Thailand to reach an international standard
      level, rendering patients good surgical outcomes comparable to developed
      countries. After successful operation, seizure free patients have become
      independent, self earning or employed. However, quality of life (QOL) in terms of
      occupational achievement and income acquisition after epilepsy surgery has never
      been studied. These indicators reflect the ultimate QOL in the aspects of actual
      independency, intact brain functions, mental health and psycho-social
      interactions. The authors therefore conduct the study on improvement of QOL after
      successful epilepsy surgery using these parameters. MATERIAL AND METHOD: One
      hundred and eleven intractable epilepsy who have become seizure free to
      worthwhile improved (Engel class I to III) after standard presurgical evaluation
      and epilepsy surgery from January 2002 to December 2004 were evaluated. The
      patients were followed up for 3 years. The occupational status and incomes were
      categorized according to the ranking of the patients' functioning levels. The pre
      and post surgery work abilities, employment and incomes were interviewed and
      compared. Mc Nemar test and paired t-test were used for statistical analyses.
      RESULTS: The average age of the 111 adults (54 males and 57 females) was 33.7 +/-
      9.2 years. Eighty two percent of the patients had temporal lobe epilepsy (TLE)
      with mesial temporal sclerosis (MTS) and underwent standard anterior temporal
      lobectomy. The rest had tumors, cortical dysplasia or scar and received
      lesionectomy or cortical resection assisted by intra-operative or intra-cranial
      EEG. The overall seizure free rate is 83.8%. The occupational status of the
      subjects was shown to improve significantly after surgery from unemployed to
      higher categories of professional achievement (p < 0.001). The number of
      unemployed and no income individuals decreased from 66 to 25 cases (62.1%
      reduction rate) after surgery (p < 0. 001). Reciprocally, the number of persons
      who achieved professional jobs with regular incomes or salaries increase from 30
      to 53 cases (43.4% increasing rate) (p < 0.001). The patients who have not
      acquired any income increment showed improvement in working ability after
      epilepsy surgery. The average annual incomes per capita shows the increasing rate
      of 45.08%, from 55,657.85 Baht (approximately U.S. dollars 1390) to 80,748.15
      Baht (approximately U.S. dollars 2018), with strong statistical significance (p <
      0.001). The improvement is best seen in seizure free than in non-seizure free
      subjects. CONCLUSION: The present study, to the authors 'knowledge, is the first
      to use work abilities, professional achievement and income acquisition to assess
      the ultimate QOL after epilepsy surgery. Most subjects have been shown to
      significantly improve their postoperative lives in terms of occupational
      accomplishment and income increment, especially in seizure free individuals. The
      need for expansion of epilepsy surgery is emphasized.

PMID- 16623031
TI  - Computer-assisted instruction in parasitology: a cross-over design.
AB  - We report here the results of the study using CAI compared to the hard copy for
      study of lessons in parasitology. We evaluated the CAI compared to hard copy
      lessons in 60 students, attending the third-year parasitology course at Faculty
      of Medicine, Chulalongkorn University, Bangkok, Thailand. The students were
      randomly divided into two groups (30 each). The lessons tested were Ascaris
      lumbricoides and Enterobius vermicularis, which were prepared as CAI and hard
      copy form. Using a cross-over design, the first group was provided CAI form on
      the topic of A. lumbricoides, then switched to hard copy form on the topic of E.
      vermicularis. The second group was provided hard copy form on the topic of A.
      lumbricoides, then switched to CAI form on the topic of E. vermicularis. After 30
      minute reading, the 10-multiple choice question test was provided for each topic.
      There was no significant difference of the scores between 2 groups. The most
      students (91.67%) had more satisfaction when using CAI compared to hard copy in
      terms of easy to use, convenient to use, less time consuming, more
      understandable, more attractive to read, and less stress for study. There were
      32.8% students complaining that reading hard copy was boring. Other comments were
      stress when reading (2%), more difficult (17.2%) and more time needed to search
      specific information (17.2%), and wasting papers (17.2%). However 58.6% still
      complained problems when using CAL. About 25% had physical discomfort (e.g.
      Headache, eye pain), and 25% had difficulty to access to use CAI (e.g. no
      computers available, problems with computer or network error). We suggested that
      instructors should create and improve CAI lessons in biomedical sciences both in
      quantity and quality (e.g. content with details, pictures, narrations).

PMID- 16623032
TI  - Happiness and related factors in pregnant women.
AB  - BACKGROUND AND OBJECTIVES: Pregnancy is a crisis in the human life cycle as an
      important turning point in aspects of anatomical, physiological and psychosocial
      changes. An unhappy pregnanus could influence the fetal growth and development
      and sense of maternal competence as well as bonding with the fetus which
      profoundly affect the nurture of the infant after delivery. The authors'purposes
      were to study happiness and related factors in pregnant women having antenatal
      care at King Chulalongkorn Memorial Hospital. MATERIAL AND METHOD: Four hundred
      and thirty-eight pregnant women from the antenatal clinic at King Chulalongkorn
      Memorial Hospital were randomly selected to complete a set of questionnaires that
      consisted of personal information, pregnant information, The Oxford Happiness
      Questionnaire (OHQ), The Maudsley Personality Inventory (MPI) and The Marital
      Satisfaction Scale (MSS). Prevalence of happiness level was classified by
      descriptive analysis. Unpaired t-test, ANOVA and Pearson's Product Moment
      Correlation analyzed related factors to happiness in pregnant woman. Also
      Stepwise Multiple Regression Analysis was used to define predictive factors for
      happiness in pregnant women. RESULTS: The sample had a high level of happiness of
      57.3%. Significant related factors to happiness were age between 31-35 years,
      high education level, high individual and family income, having saving
      deposition, no drug abuse, improved marital relationship, no conflict with
      relatives, extrovert and stable personality types and no concerns about post
      partum body image. Four predictive factors for happiness in pregnant women were
      extrovert personality, stable personality, high family income and improved
      marital relationship. CONCLUSION: Level of happiness in pregnant women could be
      predicted by type of personality, family income and marital relationship.

PMID- 16623033
TI  - Brainstem auditory evoked potentials (BAEPs) study in chronic arsenic poisoning
      patients.
AB  - OBJECTIVES: To explore the possible neurotoxicity of arsenic to auditory sensory
      pathways and evaluate roles of BAEPs in the detection of early brain damage
      resulting from arsenic exposure. DESIGN: Cross-sectional analytic study. MATERIAL
      AND METHOD: Twenty nine females with skin lesions consistent with arsenical
      dermatoses and 27 controls who met the inclusion criteria were investigatetd by
      Auditory Evoked Potentials (AEPs). Case findings resulted from a house-to-house
      survey in village 12, Ronphibun subdistrict and village 5, Saothong subdistrict,
      Nakhon Si Thammarat Province, southern Thailand in 1995. RESULTS: Differences
      between the arsenic-exposed population and the referent group regarding BAEP
      parameters, BAEP latencies and interpeak latencies were not found. CONCLUSION:
      Evidence of the abnormalities of the auditory sensory pathways was not found
      among female patients with arsenical dermtoses in Ronphibun. The role of BAEPs in
      the detection of brain damage resulting from arsenic exposure could not be
      demonstrated.

PMID- 16623034
TI  - The effect of mobile phone to audiologic system.
AB  - Mobile phones have come into widespread use. There are a lot of possible adverse
      effect to health. Use of mobile phone generate potentially harmful radiofrequency
      electromagnetic field (EMF) particularly for the hearing aspect. 98 subjects
      underwent hearing evaluations at Department of Otolaryngology, Faculty of
      Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University. 31
      males and 67females, mean age was 30.48 +/- 9.51 years old, all subjects were
      investigated the hearing level by audiometry, tympanometry, otoacoustic emission
      (OAE) and auditory brain stem evoked response (ABR). The average of using time
      were 32.54 +/- 27.64 months, 57 subjects usually used the right side and 41 the
      left side. Average time of use per day was 26.31 +/- 30.91 minutes (range from 3
      to 180 mins). When the authors compared the audiogram, both pure tone and speech
      audiometry, between the dominant and nondominant side, it indicated that there is
      no significant different. When the authors focused on the 8 subjects that used
      the mobile phone more than 60 mins per day. It indicated that the hearing
      threshold of the dominant ears was worse than the nondominant ears.

PMID- 16623035
TI  - The difference among stress and rest normal reference databases using non
      corrected, scatter corrected, and scatter with attenuation corrected Bull's eye
      myocardial perfusion scintigraphy in both genders.
AB  - OBJECTIVES: To compare 3 types of Bull's eye normal reference maps; non
      corrected, scatter corrected, and scatter with attenuation corrected Bull's eye
      in both genders. MATERIAL AND METHOD: Sixty-seven normal healthy males and
      females volunteered for the present study. After screening tests to identify low
      post-test (exercise EKG) likelihood of coronary artery disease, 41 subjects (20
      males and 21 females) had stress and rest myocardial perfusion scintigraphy
      (99mTc-sestamibi). The data were reconstructed by filtered back projection
      reconstruction in three ways as follows; (1) non-correction (NoC), (2) scatter
      elimination only (SC), (3) scatter elimination and attenuation correction
      (SC+AC). Three sets of reconstructed data of both stress and resting studies were
      added into 6 sets of Bull's eye. The data of each Bull's eve were normalized to
      100% of the maximum count. Percentage of uptake in each area was compared by t
      test statistics. RESULTS: Stress and rest count distribution of NoC and SC sets
      were lowest at the inferior wall, followed by the septal wall, anterior wall, and
      lateral wall in both genders. In the SC+AC sets; septum and lateral walls showed
      more uptake than anterior and inferior walls. A significant difference of
      percentage uptake between stress and rest images at septum in NoC and SC images
      in male and in SC image in female was observed. No difference was seen in the
      SC+AC groups. CONCLUSION: There was similarity of count distribution between NoC
      and SC images. SC+AC caused more uniform image. However; some non-uniformity was
      observed. The use of sex-independent SC+AC bull's eye is possible. Stress study
      can be omitted for bull's eye collection of normal files.

PMID- 16623036
TI  - Effects of cardiac rehabilitation on fibrinolysis in patients with coronary
      artery disease.
AB  - The aim of the present study was to demonstrate the influence of exercise
      component of a cardiac rehabilitation program on fibrinolysis in coronary artery
      disease (CAD) patients. Cardiac rehabilitation program was claimed to have an
      important role for improving quality of life and reducing the incidence of
      recurrent disease. The program used in the present study included aerobic
      exercise for 8 weeks, 4 days per week, 30 minutes per day at light to moderate
      intensity. Thirty-three male patients with CAD were recruited in the present
      study. Subjects from Thammasat University Hospital and King Chulalongkorn
      Memorial Hospital, whose age ranging from 40 to 70 years, were random assigned
      into 2 groups: control and experimental groups. The results showed that no
      significant differences in tissue plasminogen activator levels (t-PA) (both
      antigen and activity), plasminogen activator inhibitor-1 levels (PAl-1) (both
      antigen and activity) were observed in control and experimental groups after
      exercise training for 8 weeks as compared to the baseline. However significant
      improvement of fibrinolysis via a decrease in PAI-1 activity level from 16.3
      (3.7) to 14.8 (6.3) AU/ml (p < 0.024) and an increase in t-PA activity from 2.3
      (0.8) to 2.7 (0.5) IU/ml and t-PA antigen from 7.5 (2.9) to 9.2 (2.7) ng/ml (p <
      0.01) in experimental group were observed when compared between pre and post
      acute submaximum exercise (65% VO(2 peak)) at the end of the program. In addition
      the authors found a significant improvement in VO(2 peak) resting heart rate, and
      serum triglyceride level in experimental group after 8 weeks of exercise
      training. This study demonstrated that patients with CAD participating in 8 weeks
      exercise cardiac rehabilitation program at light--moderate intensity could
      improve physical fitness and physical health although there was no significant
      change of fibrinolysis. The CAD patients should be advised to enroll in this
      cardiac rehabilitation program since it did not have any harmful effect due to
      the fibrinolytic function but it also augmented the patients' physical health.

PMID- 16623037
TI  - Protein S deficiency is common in a healthy Thai population.
AB  - Currently, venous thromboembolism is a growing menace in Asians, approaching to
      that of Western countries. The most common genetic mutations causing thrombosis
      in Caucasians are factor V Leiden and prothrombin mutation. However both are very
      rare in Asians. On the other hand, natural anticoagulant protein (protein S,
      protein C and antithrombin) deficiencies are more common in Asian than in Western
      thrombotic patients. The prevalence of these deficiencies is very low in healthy
      Caucasians (0.02-0.3%). It is possible that the prevalence is higher in an Asian
      general population. However there have been very few prevalence studies to prove
      this hypothesis. Protein S deficiency was found in 3.7% (13/352, 95% confident
      interval 1.72-5.66) healthy Thais. Seven of them were type III deficiency.
      Similar to previous studies, total and free protein S levels were lower in
      females, but positively and negatively correlated with age, respectively. In
      contrast, one protein C deficiency (0.27%, 1/370) and no antithrombin deficiency
      (0/206) were detectable in our population. Furthermore, the authors found that
      antithrombin was significantly lower in women and there was a positive
      correlation between protein C activity and age. In conclusion, protein S
      deficiency is more common in Thais than in Caucasians. This result remains to be
      confirmed by a large population-based study.

PMID- 16623038
TI  - Decrease of mosquito salivary gland proteins after a blood meal: an implication
      for pathogenesis of mosquito bite allergy.
AB  - Salivary gland protein profiles ofAedes aegypti (L.) and Culex quinquefasciatus
      (Say) pre- and post-blood feeding were analyzed. SDS-PAGE studies before blood
      feeding of Ae. aegypti demonstrated 8 major polypeptide bands of 20, 35, 37, 42,
      45, 47, 70 kDa and a high molecular weight band >118 kDa, whereas those of Cx.
      quinquefasciatus demonstrated 9 major polypeptide bands of 20, 26, 36, 38, 45,
      47, 49 kDa and 2 high molecular weight bands >118 kDa. After a blood feeding,
      salivary gland polypeptides of Ae. aegypti at 35, 37, 45, 47, 70 kDa and high
      molecular weight band >118 kDa were depleted, while the polypeptide bands of 20,
      26, 36, 38 kDa were depleted in Cx. quinquefasciatus. The presented study
      suggests that these major polypeptides were introduced into vertebrate hosts when
      a mosquito took a blood meal. Further investigation in molecular, biochemical and
      immunological aspects of these salivary gland polypeptides may provide
      information for better understanding in the role of these proteins in mosquito
      bite allergy.

PMID- 16623039
TI  - Content of bone morphogenetic protein-4 in human demineralized bone: relationship
      to donor age and ability to induce new bone formation.
AB  - BACKGROUND: Bone morphogenetic proteins (BMPs) are also called growth and
      differentiation factors (GDFs) and form a subfamily of related proteins within
      the TGF-beta superfamily. BMP-4 is one ofmultifuntional growth factors with
      pleiotropic roles in many different cell types and is predominantly present in
      human bone tissue. OBJECTIVES: To analyze the content of extractable BMP-4 in
      human demineralized bone as a function of age. MATERIAL AND METHOD: Bone samples
      were ground and demineralized by exposure to 0.5 N HCl and then extracted by
      collagenase digestion. Extractable BMP-4 was analyzed using a commercially
      available enzyme-linked immunosorbent assay (ELISA). RESULTS: 63 samples of
      demineralized bone matrix (DBM) derived from 36 men and 27 women between the ages
      of 15-65 years. The extractable BMP-4 content appears to be age-dependent, with
      DBM from younger donors being most likely to have higher BMP-4 quantity. In
      addition, DBM with high osteoinductivity contained greater amounts of extractable
      BMP-4 than DBM samples with low osteoinductivity. CONCLUSION: The BMP-4 in
      demineralized bone undergoes age-related decrease that may contribute to the
      reduction of bone volume observed with aging.

PMID- 16623040
TI  - Extranodal malignant lymphoma of the upper aerodigestive tract: prevalence of
      Epstien-Barr virus (EBV) infection in King Chulalongkorn Memorial Hospital.
AB  - BACKGROUND: High frequency of Epstein-Barr virus (EBV) in the normal mucosa of
      the upper aerodigestive tract suggests that it may serve as a reservoir for the
      virus. Malignant lymphomas arising in this site may be associated with EBV.
      OBJECTIVES: To determine the prevalence of EBV infection in extranodal malignant
      lymphomas of the upper aerodigestive tract. SETTING: King Chulalongkorn Memorial
      Hospital, Thailand. DESIGN: Descriptive study. PATIENTS: 42 Thai patients who
      presented between 1998 and 2003. MATERIAL AND METHOD: The expression of EBV mRNAs
      (EBERs) of malignant lymphoma was studied by means of in situ hybridization in
      formalin-fixed, paraffin-embedded specimens. RESULTS: The recruited subjects were
      26 males and 16 females, and their age ranged from 3 to 85 years with the mean of
      51.43 years, in 4 of them human immune deficiency virus (HIV) infection was
      documented. Ten of 42 cases (23.81%) expressed EBER transcripts and were
      extranodal NK/T-cell lymphomas, nasal type (7 cases), plasmablastic lymphomas (2
      cases) and diffuse large B-cell lymphoma (1 case). Three of 4 cases (75%) of
      known HIV-seropositive cases were EBV-positive (2 plasmablastic lymphomas and 1
      diffuse large B-cell lymphoma). CONCLUSION: In the upper aerodigestive tract, EBV
      was present in some but not all malignant lymphoma. It was associated with
      extranodal NK/T-cell lymphoma, nasal type and B-cell lymphoma arising in HIV
      infected patients, but it was not found in B-cell lymphoma arising in
      immunocompetent patients.

PMID- 16623041
TI  - Evaluation of calculated low-density lipoprotein against a direct assay.
AB  - OBJECTIVES: To evalate compare the calculated LDL determined by the Friedewald
      formula when Tg < 200 mg/dL, 200-399 mg/dL, and > or =400 mg/dL against a direct
      method. MATERIAL AND METHOD: Samples from 202 participants (122 males, 80
      females, aged 20-87 years old) were determined for cholesterol, triglyceride
      (Tg), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) at
      Department of Laboratory Medicine, King Chulalongkorn Memorial Hospital (KCMH).
      LDL was determined by Friedewald formula and a direct method. RESULTS: Intra
      assay and inter-assay precisions at Tg <200 mg/dL, 200-399 mg/dL, > or =400 mg/dL
      of calculated LDL and direct LDL were 4.80%, 3.29%, 20.37%, 4.86, 8.42%, 8.32%,
      2.11%, 1.79%, 3.99%, 2.36%, 2.41% and 6.16%, respectively. The mean absolute
      biases calculated for calculated LDL against direct LDL at Tg <200 mg/dL, 200-399
      mg/dL, > or =400 mg/dL and for total samples were 4.70%, 11.73%, 63.65%, and
      7.46%, respectively. Linear regression analysis for calculated LDL vs direct LDL
      for total samples and grouped as Tg <200 mg/dL, 200-399 mg/dL, and > or =400
      mg/dL were 0.9190, 0.9796, 0.9440, and 0.7910, respectively. Intraclass
      correlation coefficient (ICC) at 95% confidence interval of calculated LDL
      against direct LDL at Tg <200 mg/dL, 200-399 mg/dL, > or =400 mg/dL and for total
      samples were 0.963, 0.930, 0.767, and 0.889, respectively. CONCLUSION: The
      present data suggested that direct LDL is superior over calculated LDL in terms
      of precision and accuracy. The present study supported that at Tg > or =400 mg/dL
      calculated LDL should not be used and the traditional cutoff of Tg <400 mg/dL for
      using Friedewald formula should be revised. In addition, regarding patient
      convenience, financial reason, and precision and accuracy of analytical method,
      direct LDL is recommended when Tg > or =200 mg/dL.

PMID- 16623042
TI  - Establishment of real-time polymerase chain reaction-based assay for quantitation
      of Epstein-Barr virus DNA in healthy donors and in patients with EBV associated
      lymphoma.
AB  - Epstein-Barr virus (EBV) is associated with several malignancies including
      nasopharyngeal carcinoma and lymphoma in immunocompromised patients. Quantitative
      monitoring of EBV DNA in these patients has recently become essential for
      management of the disease. In the present study the authors developed a rapid and
      reliable real-time PCR to quantify the EBV DNA in peripheral blood mononuclear
      cell (PBMC) using hybridization probe technique. The real-time primers and probes
      in this real-time PCR system were designed based on EBNA-1 sequence. The newly
      established real-time PCR demonstrated its high sensitivity (as few as 10 copies
      of EBV could be detected) and specificity. The intra- and inter-assay variations
      of the assay were shown to be within a 0.5-log10-difference range. A total of 2
      EBV-seronegative, 14 EBV-seropositive healthy donors and 4 patients with PCNSL
      were enrolled into the study. Our results revealed the median of EBV-DNA in
      lymphoma patients (7886 copies/10(6) PBMC or 15,150 copies /microg DNA) was
      higher than that of healthy donors (<10 copies/l0(6) PBMC or <10 copies/microg
      DNA) with statistic significance (P < 0.01). Assessment of this assay in larger
      number of donors and patients will provide clinical cut-off values which are
      essential for monitoring and diagnosis of EBV-associated diseases.

PMID- 16623043
TI  - Cross-sectional survey of hand-hygiene compliance and attitudes of health care
      workers and visitors in the intensive care units at King Chulalongkorn Memorial
      Hospital.
AB  - BACKGROUND: Hand hygiene is the most important and effective measure to prevent
      cross-infection in hospitals. Hand-hygiene campaign must be implemented as a part
      of infection control program at King Chulalongkorn Memorial Hospital (KCMH). The
      behavior attitudes, and beliefs of health care workers (HCWs) and visitors
      regarding hand-hygiene practices have never been studied in KCMH. OBJECTIVES: To
      determine the baseline compliance and assess the attitudes and beliefs regarding
      hand hygiene of HCWs and visitors in intensive care units (ICUs) at KCMH.
      MATERIAL AND METHOD: We observed hand-hygiene compliance of HCWs and visitors in
      ICUs before patient contact for eight hours. A self-administered questionnaire
      was employed to measure attitudes and beliefs about hand hygiene for two-week
      period. RESULTS: Overall hand-hygiene compliance obtained from this observational
      study was less than 50% and differed markedly among various professional
      categories of HCWs and visitors. In questionnaire-based study, patient needs
      perceived as a priority (51.2%) was the most common reason for non-compliance,
      followed by forgetfulness (35.7%), and skin irritation by hand-hygiene agents
      (15.5%). Subjects believed to improve their compliance by multiple strategies
      including available low irritating hand-hygiene agents (53.4%), information of
      current nosocomial infection rate (49.1%), and easily accessed hand-hygiene
      supplies (46.3%). Almost all subjects (99.7%) claimed to know correct hand
      hygiene techniques. Handwashing with medicated soap was perceived to be the best
      mean of hand decontamination (37.8%). CONCLUSION: Hand-hygiene compliance of HCWs
      and visitors is unacceptably low. Their knowledge, behavior attitudes, and
      beliefs toward hand hygiene need to be improved by the multimodal and
      multidisciplinary approach.

PMID- 16623044
TI  - Pneumocystis jiroveci in HIV/AIDS patients: detection by FTA filter paper
      together with PCR in noninvasive induced sputum specimens.
AB  - OBJECTIVES: To detect P. jiroveci (previously named P. carinii) by PCR using FTA
      filter paper to extract the DNA, from noninvasive induced sputum samples of
      HIV/AIDS patients. MATERIAL AND METHOD: Fifty two HIV/AIDS patients suspected of
      Pneumocystis jiroveci pneumonia (PJP) in King Chulalongkorn Memorial Hospital
      were recruited. Both cytological method and PCR with FTA filter paper technique
      were performed to detect P jiroveci from each specimen. RESULTS: The
      detectability rate of P. jiroveci infection was 21%. The PCR with FTA filter
      paper method was 4 folds much more sensitive than Giemsa staining technique. P.
      jiroveci was detected in 18% of the HIV/AIDS patients in spite of receiving
      standard PJP prophylaxis. CONCLUSION: Detection of P. jiroveci by using FTA
      filter paper together with PCR in induced sputum samples could detect more cases
      of P. jiroveci infection than by using cytological method. DNA extraction using
      the FTA filter paper was more rapid and convenient than other extraction methods.
      The causes of failure of PJP prophylaxis should be evaluated.

PMID- 16623045
TI  - Increase of genital HSV-1 and mixed HSV-1 and HSV-2 infection in Bangkok,
      Thailand.
AB  - From January 1998 to December 2004, 207 out of 1125 samples were HSV isolation
      positive and typed. Two groups of patients, Thai and foreigner, as well as site
      of infection, non-genital and genital area, were identified. The prevalence of
      non-genital HSV-1 infection from 27 samples of Thai patients was 81.84%. Out of
      180 genital samples, 39.02% HSV-1 and 43.09% HSV-2 from 123 Thai patients and
      36.84% HSV-1 and 49.12% HSV-2 of 57 foreigner patients were determined. Moreover
      mixed infection of HSV-1 and HSV-2 was found in both Thai and foreigner groups,
      17.89% and 14.04%, respectively. The prevalence of genital HSV-1 infection in
      Thai patients chronologically increases from 1.6% to 56.91% from of 1985 to 2004.
      Increase of HSV-1 genital infection and mixed HSV-1 and HSV-2 infection in Thai
      people might probably be due to changing of sexual behavior in the AIDS era.

PMID- 16623046
TI  - Etiologies of glomerular diseases in Thailand: a renal biopsy study of 506 cases.
AB  - BACKGROUND: The nationwide renal registry has not yet been organized in Thailand,
      and the literature contains no registry of renal pathologic finding across the
      Southeast Asian (SEA) countries in the modern era when electron microscopy (EM)
      is routinely available. OBJECTIVE: The aim of the present study was to examine
      the prevalence of renal pathology in Thai population. MATERIAL AND METHOD: The
      authors reviewed the case file and renal biopsy specimens of King Chulalongkorn
      University Hospital to identify all adult native renal biopsy specimens received
      from January 2001 to December 2004, investigating prevalence and clinical and
      histological data. Biopsy of renal graft and in cases of trauma and tumors the
      authors excluded. Most of the biopsy specimens obtained The authorsre analyzed
      using light microscopy (LM), immunofluorescense (IF), and EM. Final diagnosis was
      made for each patient based on clinicopathologic correlations. RESULTS: A total
      of 506 native renal biopsies were processed during this period, 69.8% were female
      and 30.2% were male. Their age average was 37 +/- 14.2 (13-80) years. The most
      common indications for renal biopsy were nephrotic syndrome and SLE (36.8%,
      34.5%, respectively), followed by asymptomatic hematuria/proteinuria in 10.9% of
      patients. Secondary glomerular diseases were dominant against primary diseases in
      all but elderly age group (>50 years), particularly LN. Among primary glomerular
      diseases, the prevalence of IgAN, focal segmental glomerulosclerosis, and
      membranous nephropathy were 31.0%, 24.9%, and 13.1%, respectively. The
      provisional clinical diagnosis was correct in three fourths (73.2%) of the SLE
      cases. Postbiopsy complications occurred in 3.3% (17/506). Gross hematuria was
      seen in 2.3% (12/506), and perinephric hemptoma in 0.79%. Three of them required
      blood transfusion but none of them died and required an invasive procedure for
      resolution. The major complications were 2 folds less than regular prevalence
      (0.6% compared to 1.3%). CONCLUSION: Although the data was collected from single
      center where EM is routinely performed, the authors believe that IgAN is the
      commonest primary GN in SEA countries. The authors are looking forward to seeing
      the nationwide registry data in Thailand and other SEA countries.

PMID- 16623047
TI  - Pulmonary alveolar proteinosis: a report of seven patients from King
      Chulalongkorn Memorial Hospital.
AB  - From 1983 to 2001, 7 patients with pulmonary alveolar proteinosis were admitted
      to the King Chulalongkorn Memorial Hospital. Presenting symptoms varied from
      asymptomatic (1 patient), progressive dyspnea on exertion (4 patients) to
      respiratory failure (2 patients). Other symptoms included dry cough and weight
      loss. Gradual onset of dyspnea could be observed by average time to hospital (7
      months). Early worsening of dyspnea and high-grade fever suggested a possibility
      of superimposed infection. Chest radiographs revealed symmetrical infiltration
      without lobar predominance. 4 of 7 patients were misdiagnosed as pulmonary
      tuberculosis before diagnosis of PAP was made. Diagnosis was made by
      bronchoscopic examination with typical lavage fluid or pathological results; only
      one case need open lung biopsy. 6 of 7 patients required lung lavage to relieve
      dyspneic symptoms. Coinfection with Nocardia and Mycobacterium tuberculosis was
      found in one patient. Prognosis was good but recurrence was common.

PMID- 16623048
TI  - The benefits of vitamin C and vitamin E in children with beta-thalassemia with
      high oxidative stress.
AB  - The present study aimed to determine the benefits of vitamin C and vitamin E as
      antioxidant supplements in beta-Thalassemia children who are at risk of iron
      overload due to multiple blood transfusion and high oxidative stress. Antioxidant
      status, oxidative products, plasma free hemoglobin, total hemoglobin and
      bilirubin were discussed. Twenty children who had laboratory confirmation of
      major beta-Thalassemia at least 6 months with history of packed red cell
      transfusion without iron chelation were recruited. The informed consent for blood
      sample collection and antioxidant medication was performed. Most patients (85%)
      had hyperferritinemia and all of them had high oxidative stress. All of them had
      low vitamin C and vitamin E level at recruitment. Three months after vitamin C
      and vitamin E supplementation, plasma vitamin C, vitamin E and glutathione were
      significantly increased, while total bilirubin was slightly decreased without
      significance. Other parameters included total antioxidant status (TAS), plasma
      and erythrocyte malondialdehyde (MDA), hemoglobin and plasma free hemoglobin had
      no differences during the study period. CONCLUSION: B-Thalassemia major children
      who had multiple blood transfusion are at risk in iron overload and high
      oxidative stress. From the present study, no significant improvement in raising
      hemoglobin and concerning low dose vitamin C is not contraindication in beta
      Thalassemia patients. Therefore, vitamin C plus vitamin E supplementation have
      benefits more than vitamin E alone in promoting antioxidant status and may
      enhance liver function as total bilirubin tends to decrease.

PMID- 16623049
TI  - Histopathologic characteristics of pulmonary adenocarcinomas with and without
      EGFR mutation.
AB  - EGFR mutation played crucial role for responsiveness of non-small cell lung
      cancers to EGFR tyrosine kinase inhibitors. Almost the mutations were present in
      adenocarcinomas. Few had studied on histopathologic correlation with EGFR
      mutation in pulmonary adenocarcinomas. To obtain better view on pathobiology of
      pulmonary adenocarcinomas, we correlated exons 19 and 21 mutations with various
      histopathologic features by dissecting particular histological patterns from 60
      surgically resected adenocarcinomas. RESULTS: Gland-forming pattern, including
      bronchiloloalveolar carcinoma (BAC), well-formed acinar, and poorly-formed acinar
      patterns more frequently contains EGFR mutations than solid pattern (72.7% vs.
      23.1%, p = 0.002). EGFR mutations of each within the gland-forming pattern are
      not significantly different. Micropapillary pattern revealed less exon 19
      mutations than the gland-forming pattern (12.5% vs. 66.7%, p = 0.018), but tended
      to have more Exon 21 mutations than the others (33.3% vs. 11.9%, p = 0.10).
      Tumors predominated by BAC pattern more commonly had exon 19 mutations than non
      BAC predominated tumors (68.8% vs. 39.5%, p = 0.046). EGFR-mutated tumors
      comprised less proportion of papillary pattern than tumors without mutation (mean
      = 1.5% vs. 11.2%, p = 0.049). Terminal respiratory unit (TRU) histology was
      associated with more EGFR mutations (72.4% vs. 42.1%, p = 0.036). Tumors smaller
      than 3.5 cm had more EGFR mutations than larger tumors (73.1% vs. 41.9%, p =
      0.018). CONCLUSION: High frequency of the mutation does not present only in BAC
      pattern, but also in well-formed and poorly-formed acinar patterns, suggesting
      them as usual spectrum of EGFR mutated adenocarcinomas. Other characteristics of
      EGFR-mutated adenocarcinomas include TRU-type histology, smaller size, and less
      solid phenotype.

PMID- 16623050
TI  - Self-medicated over the counter ophthalmic solutions in central Bangkok.
AB  - BACKGROUND: There is a paucity of research about patients' attitudes, motivations
      and expectations towards self-medicated over the counter (OTC) ophthalmic
      solutions. OBJECTIVES: To identify the attitudes, motivations and expectations of
      general population towards self-medicated OTC ophthalmic solutions. MATERIAL AND
      METHOD: 200 consecutive participants who were studying or lived in Patumwan
      District of Bangkok filled in a questionnaire in a 3-months period. RESULTS:
      67.5% (135/200) of the participants had an age range of 15-24 years old and 32.5%
      (65/200) were between 25-35 years old. Participants who were university graduates
      and currently university students were 53% and 35.5% respectively. Most history
      of illness was allergy (10/200). Half of the participants had normal vision and
      40% (80/200) were near-sighted. The factor that most influenced the use of
      solution was dust in the eye (55%-111/200). Ocular allergic symptoms, such as eye
      itching, irritation and tearing, was the second. The most frequent symptom that
      induced the use of solutions was eye itching and irritation (48.5%-97/200). The
      symptom of red or pink eye was the second (33%-66/200). 48.5% (97/200) and 53.50%
      (107/200) of participants started using the solution at the time the influencing
      symptoms occurred and used for one day respectively. 46.5% (93/200) of the
      participants realized that the solution could be use only within 1 month after
      opening. CONCLUSION: From the data of this survey, more information and knowledge
      about the use of OTC products needs to be campaigned, even among highly educated
      citizens in the center of Bangkok. Better information for patients could improve
      the safety of OTC medicines. The ways of advising patients need to be found. The
      uncertainty is, therefore, how far this trend will go and how health care
      professionals and consumers will resspond.

PMID- 16623051
TI  - Role of forensic doctors in Thailand's tsunami: experiences from Chulalongkorn
      Medical School.
AB  - Personal identification was the major task of forensic doctors in Thailand's
      Tsunami. Identification can be done by visual identification, circumstantial
      evidence and physical evidence. Among the physical evidences dental data is the
      most effective method of identification, followed by fingerprint and DNA. A
      disaster Identification team should be set up to handle the problems and plan for
      the future.

PMID- 16623052
TI  - Tourette's syndrome: old syndrome, new insights and new treatment.
AB  - Recognized for over 300 years, Tourette's syndrome was originally ascribed as a
      rare bizarre psychogenic illness. Because of recent advances in research on
      Tourette's syndrome, this disorder is not only the rarity once thought, but also
      a common, biological, genetic disorder with a spectrum of neurobehavioral
      manifestations that wax and wane during its entire natural course. In addition to
      standard neuroleptics, much progress in Tourette's syndrome research has widened
      its pharmacotherapy to include alpha2-adrenergic agonists and atypical
      neuroleptics as well as behavioral modification, adjustments, and different
      surgical approaches. Despite a myriad of reports, there are still many unresolved
      facts, which stimulate research into the underlying mechanisms of this complex
      neuropsychiatric disorder. We anticipate that continued success of research in
      this area will lead to molecular insights, identification of vulnerable genes,
      and eventually novel therapies that can target all aspects of this complex
      disorder.

PMID- 16623053
TI  - Montelukast in general pediatric practices.
AB  - Allergic diseases, e.g., allergic rhinitis, atopic dermatitis and asthma, are
      common problems in children. Researches on the pathogenesis of allergic diseases
      have led to the development of new specific antiinflammatory medications,
      including Montelukast, which blocks the interaction of cysteinyl leukotrienes to
      their receptors and resulting downstream events. Several studies have
      demonstrated the effect of regular Montelukast therapy on asthma, allergic
      rhinitis, viral-induced wheezing in bronchiolitis and chronic rhinitis symptoms.
      Evidence base medicine now shows that Montelukast can be used as a monotherapy in
      mild persistent asthma and can be an add-on drug to inhaled corticosteroid (ICS)
      in moderate to severe persistent asthma. Even in allergic rhinitis, Montelukast
      has a role in controlling rhinitis symptoms. Montelukast demonstrated a safety
      profile similar to placebo and more safety than ICS. Moreover Montelukast can
      improve quality of life in patients with asthma and comorbid allergic rhinitis.

PMID- 16623054
TI  - Endoscopic management of pancreatic cancer.
AB  - Endoscopic treatment of pancreatic malignancy can be considered as an alternative
      treatment option in inoperable patients. Endoscopic retrograde cholangio
      pancreatography (ERCP) plays a key role, allowing diagnosis, collection of
      cytologic, biopsy specimens, and insertion of biliary and pancreatic stents. A
      major problem is the patency of plastic stents that will eventually clog on
      average after 3 to 4 months. Self-expandable metallic stents have longer patency,
      but they can also become occluded by tumor ingrowth or overgrowth. Furthermore,
      metallic stents are much more expensive and their uses may be considered in
      patients with longer life expectancy. ERCP can be performed on an outpatient
      basis in selected patients, reducing costs related to hospitalization. A team
      approach is mandatory to obtain the best results.

PMID- 16623055
TI  - Advances in alternative pharmacotherapy of ADHD.
AB  - Several alternatives to psychostimulants have been developed and expanded the
      variability of the treatment of ADHD. Clonidine is a good option for managing
      core behavioral symptoms, especially hyperactivity and impulsivity. Bupropion and
      venlafaxine seem potentially promising. Significant new options include
      norepinephrine reuptake inhibitors, such as atomoxetine, and possibly selective
      dopamine agonists. Central anticholinesterases, such as donepezil, may improve
      core ADHD symptoms.

PMID- 16623056
TI  - Investigation and treatment of asthma.
AB  - Asthma is one of the most common chronic respiratory diseases presenting with a
      variety of symptoms from cough, chest tightness, wheeze, difficulty breathing and
      in many cases persistent dyspnea. The individual has been effected usually spends
      a significant amount of time and financial resources in order to control the
      symptoms. Even though asthma has been known for more than several decades, the
      medications for the condition are relatively limited. This article has reviewed
      currently available guidelines, classifications, investigations for the diagnosis
      and treatment recommendations of asthma for both the general practitioners and
      the specialists who mainly taking care of patients with this chronic airway
      condition.

PMID- 16623057
TI  - Naming disorders anomic aphasia.
AB  - Naming disorders, as a symptom, is always found in all aphasic patient. The
      patient although has a clear understanding of what he is trying to name or what
      he is told to write, but needs longer time or can not articulate it. Sometimes he
      substitutes with other words or even produces jargon words. Assessment and
      intervention are complicate and delicated the most important functions of the
      clinician. The goal of word-retrieval activities in treatment is to improve the
      patient's cognitive performance and to teach method to circumvent the vocabularly
      when needed.

PMID- 16623058
TI  - Is there any role of acid reducing gastric surgery in peptic ulcer perforation?
AB  - Helicobacter pylori (H. pylori) is known to be the prime factor of peptic ulcer
      disease as well as NSAID usage. Although medical treatment of the bacteria can
      eliminate the problem for more than 90% of the infected people but the cost of
      treatment is high then acid reducing gastric surgery still has a definite role.
      The prevalence of H. pylori in peptic ulcer perferation is still unknown also
      whether vagotomy and gastrectomy could eradicate H. pylori. Now laparoscopic
      surgery especially the simple repair of the perforation has became routinely used
      in many part of the world. So acid reducing gastric surgery is a good choice in
      chronic user of NSAID and also an option for people who have H. pylori infection.

PMID- 16623059
TI  - Perineum push-up device to facilitate transabdominal suturing of the lower
      rectum.
AB  - Pressure on the perineum by the fist facilitates the placement of sutures into
      the rectal remnant, but put the assisting surgeon on an awkward and strenuous
      posture. The perineum push-up device to facilitate transabdominal suturing of the
      lower rectum was invented. The assisting surgeon can push up the perineum more
      comfortably with his abdominal wall or thigh. The device was tested in fifteen
      patients. The average distance that can be pushed up is 4.2 cm, which is a
      significant distance, facilitating in the maneuver of the distal rectal stump.

PMID- 16623060
TI  - The third world health status of black American males.
AB  - In contrast to their white counterparts, black men in the United States live
      sicker and die younger. This longstanding phenomenon is sharply reflected in the
      poor international health status of black males. The NMA president discusses
      major health issues facing black males and posits a multidimensional strategy for
      addressing racial disparities in men's health, with a national focus on health
      promotion and disease prevention, improving healthcare quality and access, and
      eliminating structural inequities.

PMID- 16623061
TI  - Social ecological predictors of prostate-specific antigen blood test and digital
      rectal examination in black American men.
AB  - BACKGROUND: Black American men continue to suffer disproportionately from
      epidemically higher rates of prostate cancer. We hypothesize that complex reasons
      for persistently higher death rates of prostate cancer in this group are steeped
      in social factors associated with health access. METHODS: We utilized data from
      the It's All About U prostate cancer prevention study among black men to
      investigate: 1) what social ecological factors were predictive of prostate
      specific antigen (PSA) testing and digital rectal examinations (DRE); 2) if black
      men were aware of prostate cancer screening and, if screening was available,
      would they take the PSA and DRE? Quantitative cross-sectional data from a cohort
      of 276 black men with no diagnosis of prostate cancer were analyzed to identify
      characteristics, beliefs, practices and attitudes of this group toward prostate
      cancer screening. We created a social ecological model to examine which social
      factors (i.e., environmental, personal, person/environment interplay, black
      culture and institutional policy) were predictive of PSA and DRE, PSA only and
      DRE only. To reduce data and identify data patterns, factor analyses (tested for
      reliability by calculating Cronbach alpha scores) were performed. Variables were
      standardized with Z scores and analyzed with predictive analytic software
      technology (SPSS, version 12). A multivariate binary logistic regression was
      conducted to identify predictors of PSA and DRE. RESULTS: A significant predictor
      of both PSA and DRE was the physician's direct prostate cancer communication
      message (P<0.010). Significant correlations exist in PSA and DRE outcomes with a
      physician's engaging communication style (P<0.012), encouragement to screen
      (P<0.001) and sharing prostate cancer information (P<0.001); as was men
      understanding the serious risk of prostate cancer (P<0.001), culture (P<0.004),
      positive interaction with healthcare staff, significant other(s) and providers
      (P<0.001), and environmental dimensions (P<0.006). A profile of four major self
      reported barriers to screening were identified (i.e., fear, internal locus of
      health, comfort level and external locus of health). Lastly, men who utilized
      health systems with a prostate cancer screening policy had high percentages of
      PSA and DRE (63.3%), PSA only (70.9%) and DRE only (81.7%). CONCLUSION: A
      physician's aggressive, positive engagement in shared decision-making, tailored
      social influences promoting prostate cancer prevention among black men, as well
      as institutional screening policy, has the potential to increase early detection
      and reduce morbidity among this group.

PMID- 16623062
TI  - Factors influencing behavioral intention regarding prostate cancer screening
      among older African-American men.
AB  - PURPOSE: To assess factors associated with perceptions of prostate cancer
      screening among African-American men aged > or = 55 years based upon items
      developed using the Preventive Health model (PHM). RESEARCH APPROACH: Focus group
      research and thematic coding using content analysis. SETTING: A large midwestern,
      private, nonprofit health system. PARTICIPANTS: African-American men aged > or =
      55 years. Focus group 1 included 10 men who ranged in age from 55-87 years, with
      a mean age of 73.4 years. The 11 participants in focus group 2 ranged in age from
      55-81 years, with a mean age of 68.7 years. METHODOLOGICAL APPROACH: Focus group
      questions were developed based on the conceptual framework of the PHM. African
      American men aged > or = 55 years were randomly selected from the patient
      population of the healthcare system to participate in one of two focus groups.
      Content analysis was used to code the focus group transcripts. MAIN RESEARCH
      VARIABLES: Self-reported perceptions of prostate cancer screening. FINDINGS:
      Major themes emerging from the focus groups related to prostate cancer screening
      include: lack of knowledge regarding cancer, fear of cancer, confusion between
      prostate cancer screening and prostate cancer diagnostic tests, encouragement by
      others as motivation for cancer screening, intergenerational transfer of health
      information, lack of health insurance coverage as a barrier to prostate cancer
      screening and treatment, and limited availability of screening clinic hours
      during nonworking hours. INTERPRETATION: The information gained from this study
      could be used to develop interventions promoting informed and shared decision
      making by patients and their providers regarding prostate cancer screening.

PMID- 16623063
TI  - Prostate cancer screening and detection in inner-city and underserved men.
AB  - CONTEXT: In the era of serum prostate-specific antigen (PSA) screening, the
      incidence of prostate cancer has increased dramatically. Simultaneously however,
      stage migration has occurred, and treatment outcomes have improved. Inner-city
      men have lower screening rates and, thus, may be diagnosed with more advanced
      disease that it less likely to be successfully treated. OBJECTIVE: To assess the
      detection rate of prostate cancer and tumor stage at presentation in inner-city
      men. DESIGN, SETTING, AND PATIENTS: A retrospective cohort of 368 men underwent
      transrectal ultrasound needle-guided biopsy at an inner-city hospital from
      January 2003 to May 2005. Clinical and pathologic data were collected and
      analyzed. MAIN OUTCOME MEASURES: Clinic and hospital records were reviewed for
      several key outcomes, including prostate cancer incidence, tumor stage and tumor
      grade. RESULTS: The median age of the cohort was 67 +/- 9.1 years (range, 23-93
      years). Prostate cancer was diagnosed in 44% of subjects (161/368). The median
      PSA level at the time of diagnosis was significantly higher in African-American
      men than in Caucasian men (9.82 vs. 5.97 ng/mL, P=0.008). Abnormally high serum
      PSA levels (>20 ng/mL) were present in disproportionately more African-American
      men than Caucasian men with prostate cancer (32.9% vs. 19.7% P=0.011). African
      American men in this inner-city cohort also had a higher incidence of advanced
      disease or distant metastasis (T3/T4, N1, or M1) than did Caucasians (16.1% vs.
      3.8%; P=0.045). CONCLUSIONS: Compared with inner-city Caucasian men,
      disproportionately more inner-city, African-American men present with advanced
      prostate cancer. This observation warrants prostate cancer education and
      consideration of early detection programs in underserved inner-city communities.

PMID- 16623064
TI  - Managing the low-socioeconomic-status prostate cancer patient.
AB  - Management of patients with low socioeconomic status and/or low literacy who have
      prostate cancer presents a challenge to healthcare professionals. Improving
      treatment outcomes for these men requires specific educational programs to
      provide a better understanding of prostate cancer including careful posttreatment
      follow-up to ensure they have recovered well, that the cancer is not progressing
      and that complications are not proving troublesome. Practice nurses and health
      educators/navigators can play an important role in achieving these objectives.
      Education and knowledgeable advice can lead to earlier diagnosis of prostate
      cancer, improved patient participation in the treatment decision-making process
      and effective management of posttreatment complications.

PMID- 16623065
TI  - Physician-patient discussions about prostate-specific antigen test use among
      African-American men.
AB  - BACKGROUND: The purpose of this study was to examine the associations between
      physician-patient discussions, demographic and health-related variables, and PSA
      test use. Of the previous studies that examined physician-patient discussions
      about PSA test use, none focused on African-American men. METHODS: Using a sample
      of African-American men (N=739) aged > or = 40 years who had participated in the
      National Health Interview Survey (NHIS) 2000, we assessed demographic, health
      status and other variables related to two PSA test use outcomes: 1) had a PSA
      test within the past year, and 2) had > or = 3 PSA tests within the past five
      years. RESULTS: More than three-fourths (76.6%) of our sample reported that their
      doctors had discussed with them the advantages and disadvantages of the PSA test
      before administering it. The bivariate analysis showed a number of variables
      positively associated with PSA test use including men aged > or = 50, having
      health insurance coverage and having participated in physician-patient
      discussions about the test. DISCUSSION: Despite the high percentage of men who
      had discussions with their doctor, there was a large number of men who had
      neither heard of nor undergone a PSA test. More efforts should be made by the
      healthcare community to promote prostate cancer screening education and physician
      patient discussions.

PMID- 16623066
TI  - Roots of prostate cancer in African-American men.
AB  - To fully understand the role of genetics and environment (biotic, abiotic and
      sociocultural) in the prostate cancer disparity experienced by African-American
      men, this paper examined the rates of prostate cancer among African-American men
      and one of their ancestral populations in west Africa. Data sources were from the
      World Health Organization (WHO) and reported hospital records in the literature.
      Based on the WHO's worldwide cancer data, west African men have much lower
      prostate cancer incidence and mortality compared to African-American men. For
      example, compared to Nigerian men, African-American men are >10 times likely to
      develop prostate cancer and 3.5 times likely to die from the disease. However,
      contrary to the global ranking by WHO, there is documented evidence in the
      literature indicating that prostate cancer in at least one west African country
      is similar to rates found in the United States and in Caribbean Islands. To
      better address prostate cancer disparity, future studies should study populations
      and subgroups from central and west Africa, the original source population for
      African Americans.

PMID- 16623067
TI  - African-American men's perceptions of health: a focus group study.
AB  - African-American men are disproportionately affected by preventable medical
      conditions, yet they underutilize primary care health services. Because
      healthcare utilization is strongly dependent on health beliefs, the purpose of
      this qualitative study was to identify and explore African-American men's
      perceptions of health and health influences. We conducted eight focus group
      interviews with select subgroups of African-American men, including adolescents,
      trauma survivors, HIV-positive men, homeless men, men who have sex with men,
      substance abusers, church-affiliated men and a mixed sample (N=71). Definitions
      of health, beliefs about health maintenance and influences on health were
      elicited. Participants' definitions of health went beyond the traditional
      "absence of disease" definition and included physical, mental, emotional,
      economic and spiritual well-being. Being healthy also included fulfilling social
      roles, such as having a job and providing for one's family. Health maintenance
      strategies included spirituality and self-empowerment. Stress was cited as a
      dominant negative influence on health, attributed to lack of income, racism,
      "unhealthy" neighborhoods and conflict in relationships. Positive influences
      included a supportive social network and feeling valued by loved ones. This study
      provides insight into African-American men's general health perceptions and may
      have implications for future efforts to improve healthcare utilization in this
      population.

PMID- 16623068
TI  - Effects of gender-matching and racial self-labeling on paranoia in African
      American men with severe mental illness.
AB  - OBJECTIVE: The present study examined the effects of gender-matching and racial
      self-labeling on the paranoid symptoms of African-American men with severe mental
      illness. It was hypothesized that gender matching would: 1) reduce self-reports
      of both interpersonal and cultural paranoia in these male participants with
      severe mental illness, and 2) the gender effect would be strongest among those
      patients who racially self-label as African-American. METHOD: One-hundred-twenty
      four African-American male psychiatric patients were interviewed by a male or
      female black psychologist. A multivariate analysis of variance (MANOVA) was
      conducted with the Fenigstein Paranoia Scale (FPS) and Cultural Mistrust
      Inventory (CMI) as dependent variables, and the male gender-matched group (0=no,
      1=yes) and racial self-labeling as the independent variables controlling for age;
      education; never married (0=no, 1=yes); diagnosis of schizophrenia (0=no, 1=yes);
      need for approval; self-esteem; and the scales of Distrust, Perceived Hostility
      of Others, and False Beliefs and Perceptions from the Psychiatric Epidemiology
      Research Interview. RESULTS: There was a significant main effect for male gender
      matching on the FPS. Participants in the male gender-matched group scored lower
      than the other group on the FPS. For the CMI, there was a significant interaction
      of male gender match by racial self-labeling effect. Participants who were male
      gender-matched and self-labeled as African-American reported the highest scores
      on the CMI. CONCLUSION: The findings provide partial support for the hypotheses.
      Both gender-matching and racial identity together may be important considerations
      for black males needing mental health services.

PMID- 16623069
TI  - Postoperative radiotherapy in the treatment of male breast carcinoma: a single
      institute experience.
AB  - BACKGROUND: To evaluate the outcomes of radiation therapy treatment of male
      patients with breast cancer in our single institutional cohort and discover
      possible adverse prognostic factors. METHODS: We retrospectively evaluated 42
      male patients (median age 55; range 33-77 years) with breast cancer. Patients
      were irradiated postoperatively in 2 Gy/fraction/day to chest wall +/-
      lymphatics. RESULTS: Median follow-up was 29 months. Eleven patients had
      neoadjuvant and 36 patients had adjuvant Adriamycin-based chemotherapy. Nine
      patients (21%) had local or regional, two (5%) had distant, and one (2.5%) had
      both local and distant disease at the time of analysis. The actuarial five-year
      Overall Survival (OS) was 77%, whereas the actuarial five-year Disease-Free
      (DFS), Locoregional Recurrence-free (LRRFS), and Distant Metastases-Free (DMFS)
      survival rates were 45%, 69% and 66%, respectively. Univariate analysis of
      variables, including patient characteristics, treatment modalities and factors,
      and tumor characteristics, failed to show an association with LRRFS and DFS
      except percent positive nodal involvement > or = 30% and 50%. CONCLUSION: Though
      radiotherapy seems quite effective in reducing local recurrence, we have revealed
      that male breast cancer patients in our cohort with extensive nodal involvement
      (PPNI >30% and 50%) appeared not to have had a significant benefit from
      postmastectomy irradiation and adjuvant CMF-based chemotherapy.

PMID- 16623070
TI  - Preventing HIV infection among young immigrant Latino men: results from focus
      groups using community-based participatory research.
AB  - Latinos in the United States have been disproportionately affected by the
      intersecting epidemics of HIV and sexually transmitted diseases (STDs). Using a
      community-based participatory research (CBPR) approach to problem identification
      and exploration, a total of 74 Latino men (mean age 22.3, range 18-37) residing
      in an urban city in northwest North Carolina participated in one of eight focus
      groups on sexual health. Among the findings of this study, >75% of participants
      reported Mexico as their country of origin; other participants reported being
      from Central and South American countries. Qualitative data analysis identified
      13 themes, which were grouped into the following three domains: 1) psychosocial
      factors identified as influencing sexual risk health behaviors; 2) system-level
      barriers to sexual health; and 3) characteristics of potentially effective HIV
      prevention intervention approaches. The study findings suggest that community
      based, male-centered interpersonal networks that provide individual and group
      education and skill-building and incorporate curanderos (Latino healers) and
      bilingual experts may be important elements of potentially effective intervention
      approaches to reach Latino men, who have been inaccessible to conventional HIV
      prevention programs.

PMID- 16623071
TI  - Predictors of condom use among a sample of male inmates: a social cognitive
      perspective.
AB  - The primary purpose of this study was to determine factors that predict condom
      self-efficacy among a sample of soon-to-be-released adult male inmates with
      respect to self-reported HIV/AIDS risk behaviors. Approximately 230 inmates had
      agreed to enroll in the study. This analysis is based on completed baseline
      surveys from 187 inmates. Data were collected at baseline (prior to implementing
      the intervention) on self-reported condom self-efficacy HIV/AIDS risk behaviors.
      Findings support that, requesting that your partner uses condoms every time they
      had sex was the strongest indicator of self-reported condom self-efficacy by
      inmates in the sample (p<0.01). Findings also suggest that engaging in sexual
      activity after smoking marijuana, limiting the number of sex partners and asking
      partners' HIV status were significant predictors for the dependent variable of
      condom self-efficacy (p<.05); engaging in sexual activity after drinking was not
      (p<0.11). Findings suggest that it may be wise to take a best-practice approach
      using former inmates as peer educators if health-based interventions are to be
      delivered to soon-to-be-released adult male inmates.

PMID- 16623072
TI  - Body mass index relates to males with posttraumatic stress disorder.
AB  - INTRODUCTION: We looked at the relationships among posttraumatic stress disorder
      (PTSD), body mass index (BMI) and socioeconomic status (SES) in a newly formed
      PTSD program at the Hunter Holmes McGuire Veterans Affairs Medical Center in
      Richmond, VA. METHODS: We reviewed 265 records and then selected only black and
      white male veterans (n=252) for study. Variables were: 1) age, 2) decade of life,
      3) height, 4) weight, 5) sex, 6) race, and 7) SES (estimated using priority group
      status). Low income is an important variable determining priority group status.
      RESULTS: About two-thirds of the veterans were in the age range of 50-59 years
      (Vietnam veterans). Their mean BMI was 30.2 +/- 5.6 kg/m2, and this value did not
      separate by race. Far exceeding national numbers, 84.1% of our veterans were
      either overweight or obese. Veterans in the lower priority groups had greater
      (p=0.029) BMIs than their counterparts in higher priority groups. CONCLUSIONS:
      The pervasiveness of overweight and obesity in our PTSD population was profound.
      Our observations suggest that low SES is a likely contributor to veterans in
      lower priority groups having greater BMIs than veterans in higher priority
      groups.

PMID- 16623073
TI  - Isolated office hypertension: association with target organ damage and
      cardiovascular risk indices.
AB  - BACKGROUND: Isolated office hypertension (IOH) has been accepted as a benign
      condition by some researchers, whereas others believe that it is associated with
      cardiovascular abnormalities and increased cardiovascular risk. The aim of this
      present study was to evaluate the effects of IOH on target organ damage and
      cardiovascular risk indices. METHODS: Arterial blood pressure (BP) measured in
      the office and by 24-hour ambulatory blood pressure measurement (ABMP), carotid
      intima-media thickness (CIMT), left ventricular mass index (LVMI), cardiothoracic
      index (CTI), duration of QTc, 24-hour microalbuminuria, fibrinogen, C-reactive
      protein (CRP), total cholesterol, low-density-lipoprotein (LDL) cholesterol, high
      density-lipoprotein (HDL) cholesterol and triglyceride levels were evaluated.
      Thirty-three subjects with IOH (office BP > or = 140/90 mmHg and daytime
      ambulatory BP <135/85 mmHg), 17 patients with sustained hypertension (office BP >
      or = 140/90 mmHg and daytime ambulatory BP > or = 135/85 mmHg), and 17
      normotensive control subjects were recruited in the study. The three groups were
      matched for age, sex and body mass index. RESULTS: CIMT was greater in patients
      with IOH than in normotensive subjects, and it was significantly lower than that
      of sustained hypertension patients. Significantly higher LVMI was determined in
      subjects with IOH compared to normotensive subjects. CTI, QTc, microalbuminuria,
      fibrinogen, CRP, total cholesterol, LDL cholesterol, HDL cholesterol and
      triglyceride levels did not differ significantly among the three groups.
      CONCLUSIONS: IOH causes significant target organ damage and should not be
      regarded as a benign condition.

PMID- 16623074
TI  - Evaluating the impact of a hypertension program for African Americans.
AB  - Although hypertension affects all racial and ethnic groups, its prevalence is
      highest in the African-American community. The goal of Healthy People 2010 is to
      reduce hypertension among African Americans from 40% to 16%. Although current
      levels remain high, culturally sensitive, community-based clinical projects might
      be helpful in addressing this problem. The goal of this study was to assess
      whether a community-based clinic's program was effective in improving blood
      pressure control among a sample of 134 African-American adults. The program
      design involved health education and physical fitness classes offered over a nine
      month period, with blood pressure checks being conducted pre- and postphases to
      determine whether the program was effective in controlling high blood pressure.
      Health questionnaires were also administered pre- and posttest to assess whether
      health behaviors and perceived health status were influenced by the project. Two
      thirds (70%) of the sample had high blood pressure at baseline and 43% at program
      conclusion. This was a statistically significant difference (p=0.003). Overall
      self-reported health survey results indicated improved health behaviors and
      health status changes. Findings suggest that culturally sensitive, community
      based clinic programs that incorporate both health education and physical fitness
      might be effective in reducing hypertension among African Americans.

PMID- 16623075
TI  - Irbesartan/HCTZ fixed combinations in patients of different racial/ethnic groups
      with uncontrolled systolic blood pressure on monotherapy.
AB  - The IrbesartaN/hydroChlorothiazide (HCTZ) bLood pressUre reductionS In diVErse
      patient populations (INCLUSIVE) trial was a multicenter, prospective, open-label,
      single-arm study evaluating the efficacy and safety of irbesartan/HCTZ fixed
      combinations in patients > or = 18 years old with uncontrolled systolic blood
      pressure (SBP, 140-159 mmHg; 130-159 mmHg for type-2 diabetes mellitus patients)
      after > or = 4 weeks of antihypertensive monotherapy. This analysis focused on
      different racial/ethnic subgroups. Treatment was sequential: placebo (4-5 weeks),
      HCTZ 12.5 mg (two weeks), irbesartan/HCTZ 150/12.5 mg (eight weeks) and
      irbesartan/HCTZ 300/25 mg (eight weeks). Overall, 515 Caucasians, 191 African
      Americans and 119 Hispanics/Latinos completing placebo treatment were enrolled.
      Mean SBP changes from baseline (placebo treatment end) to week 18 were -21.5 +/-
      13.8 mmHg for Caucasians, -20.7 +/- 16.5 mmHg for African Americans and -22.9 +/-
      13.2 mmHg for Hispanics/Latinos, respectively (p<0.001 for each). Mean diastolic
      BP (DBP) changes were statistically significant (p<0.001) and similar among
      racial/ethnic subgroups. By week 18, 70% (95% CI, 66%, 74%) of Caucasian, 66%
      (95% CI, 59%, 74%) of African-American and 65% (95% CI, 57%, 74%) of
      Hispanic/Latino patients achieved dual SBP/DBP goal. Treatments appeared to be
      well tolerated. In conclusion, irbesartan/HCTZ treatment provided SBP/DBP goal
      attainment in approximately two-thirds of Caucasian, African-American and
      Hispanic/Latino patients with SBP uncontrolled on antihypertensive monotherapy.

PMID- 16623076
TI  - Simvastatin treatment improves endothelial function and increases fibrinolysis in
      patients with hypercholestrolemia.
AB  - OBJECTIVES: Statins reduce cardiovascular events by cholesterol-lowering as well
      as nonlipid-related actions. Thrombin activatable fibrinolysis inhibitor (TAFI)
      is a recently identified independent risk factor of thrombosis. Endothelial
      dysfunction is also a strong predictor of cardiovascular events. The aim of this
      study was to assess the effects of simvastatin treatment on circulating TAFI
      concentrations and endothelial function in patients with hypercholesterolemia.
      METHODS: Thirty-five patients (19 female, mean age 48 +/- 7 years) with
      hyperlipidemia were recruited into the study. Simvastatin was administered, 40 mg
      daily, for eight weeks to all subjects. Study subjects did not receive any
      medication except for lipid-lowering therapy during the follow-up period.
      Endothelial function was evaluated by flow-mediated dilation (FMD) from the
      brachial artery of the patients. Plasma lipid parameters, TAFI levels and
      endothelial function were measured before and after simvastatin treatment.
      RESULTS: Treatment with simvastatin showed a significant decrement in plasma
      total cholesterol, LDL cholesterol and triglyceride levels (p<0.05). Plasma TAFI
      levels were also significantly decreased after simvastatin treatment [median 17.0
      (range 0.4-93.7) mcg/mL versus median 6.9 (range 0.8-63.0) mcg/mL, p<0.001]. Mean
      FMD was measured 7.7 +/- 2.5% at baseline and significantly improved after
      treatment (13.0 +/- 1.4%) (p=0.001). CONCLUSION: Our findings of decreased TAFI
      levels may reflect the beneficial effect of simvastatin treatment on
      fibrinolysis, and improved endothelial function may suggest the improved future
      cardiovascular events in hyperlipidemic patients.

PMID- 16623077
TI  - QT dispersion in adult hypertensives.
AB  - Increased QT dispersion is associated with sudden cardiac death in congestive
      cardiac failure, hypertrophic cardiomyopathy and following myocardial infarction.
      Patients with hypertension--in particular, those with left ventricular
      hypertrophy (LVH)--are also at greater risk of sudden cardiac death. We examined
      whether QT dispersion, which is easily obtained from a routine ECG, correlates
      with LVH. One-hundred untreated patients with systemic hypertension and 78
      normotensives had QT dispersion measured manually from a surface 12-lead
      electrocardiogram and two-dimensional echocardiography performed to measure
      interventricular septal thickness, posterior wall thickness and left ventricular
      internal diameter. Office blood pressure was also recorded. Multivariate analysis
      demonstrated significant relationships between QT dispersion and office systolic
      blood pressure, and left ventricular mass index. Manual measurement of QT
      dispersion might be a simple, noninvasive screening procedure to identify those
      hypertensives at greatest risk of sudden cardiac death in a third-world country.

PMID- 16623078
TI  - Sexual dysfunction in female hypertensives.
AB  - PURPOSE: Hypertension and its treatment are known to produce sexual dysfunction
      in males. In our culture, women are not free to discuss issues of sexuality with
      their doctors. Hence, this phenomenon has not been explored in them.
      Notwithstanding this, cases occur in practice where noncompliance with dire
      consequences result from sexual dysfunction. This study was done to determine if
      any dysfunction existed among women as is commonly reported in males.
      METHODOLOGY: As part of a larger study on serum uric acid and lipid profile of
      adult Nigerian hypertensives, we sought information on sexual function in
      females. One group was newly diagnosed and treatment naive, while the other was
      made up of known hypertensives on thiazides. The third group consisted of
      normotensive age-matched controls. FINDINGS: Six out of 44 (13.6%) in the first
      group, five out of 29 (17.2%) in the second group and two out of 43 (4.7%) in the
      control group reported sexual dysfunction. The commonest aspect encountered was
      reduced desire for intercourse. CONCLUSION: There was a tendency for hypertensive
      women to have more sexual dysfunction even before treatment than did controls.
      Larger studies should be undertaken and clinicians should probe this subject if
      poor compliance is suspected.

PMID- 16623079
TI  - Sources of variability in John Henryism.
AB  - OBJECTIVES: To decompose sources of individual differences in coping as measured
      by John Henryism among African Americans. METHODS: Analyses described in this
      study are based on the pairwise responses from 180 pairs of same-sex, African
      American twin pairs who participated in the Carolina African-American Twins Study
      of Aging (CAATSA). The sample consisted of 85 monozygotic (MZ) and 95 dizygotic
      (DZ) twin pairs. RESULTS: Environmental factors account for most of the variance
      (65%) in John Henryism scores, with the remaining variance attributable to
      additive genetic factors (35%). The test of the genetic component suggested that
      the 35% represented a statistically significant proportion of variance.
      CONCLUSIONS: The vast majority of recent studies on African Americans and health
      outcomes have focused on the impact of psychosocial factors on diseases such as
      hypertension and diabetes, with relatively little attention to possible genetic
      contributors. Previous research on psychosocial indices and their relationship to
      cardiovascular health among African Americans has focused on assessment and
      epidemiological explorations rather than understanding the etiology of
      variability in such measures.

PMID- 16623080
TI  - Elderly patient with delirium after myocardial infarction.
AB  - Delirium is a transient global disorder of cognition. Almost any medical illness
      or medication can cause delirium. Here, we report a 71-year-old male who
      presented to the emergency department with a sudden change in mental status,
      which later resolved. An electrocardiogram was consistent with acute myocardial
      infarction. The patient later developed symptoms of delirium, and haloperidol was
      administered. The symptoms did not resolve, and risperidone was initiated
      instead. The patient subsequently became hypotensive, and treatment was again
      changed to olanzapine. He returned to full consciousness with olanzapine
      treatment. When the potential hypotensive effects of haloperidol and risperidone
      are taken into consideration, in patients with high cardiac risk, olanzapine may
      provide a better option for the treatment of delirium.

PMID- 16623081
TI  - Unusual course of infective endocarditis: acute renal failure progressing to
      chronic renal failure.
AB  - Infective endocarditis is an infection of the endocardium that usually involves
      the valves and adjacent structures. The classical fever of unknown origin
      presentation represents a minority of infective endocarditis. The presented case
      was a 21-yearold young lady presenting with acute renal failure and fever to the
      emergency room. Cardiac auscultation revealed a soft S1 and 4/6 apical
      holosystolic murmur extended to axilla. Echocardiography showed mobile fresh
      vegetation under the mitral posterior leaflet. She was diagnosed as having
      infective endocarditis. Hemodialysis was started with antimicrobial therapy.
      However, because of the presence of severe mitral regurgitation with left
      ventricle dilatation and large mobile vegetation, mitral prosthetic mechanical
      valve replacement was performed. Although treated with antibiotics combined with
      surgery, renal functions were deteriorated and progressed to chronic renal
      failure.

PMID- 16623082
TI  - Severe hypertriglyceridemia-induced pancreatitis during pregnancy.
AB  - Chylomicronemia syndrome is a rare disorder characterized by the presence of
      chylomicrons in the fasting state. An acute and potentially life-threatening
      complication of chyiomicronemia syndrome is severe acute pancreatitis. We report
      a case of a 24-year-old primigravida with severe hypertriglyceridemia-induced
      pancreatitis. We reviewed the clinical course and treatment of
      hypertriglyceridemia-induced pancreatitis. She was admitted in the 37th week of
      gestation with severe abdominal pain, which was radiating to the back, and having
      uterine contractions. Cesarean delivery was performed under spinal anesthesia,
      and a healthy male infant was born. Intraoperative findings included milky
      peritoneal fluid collection. Elevated pancreatic enzymes with significant
      hypertriglyceridemia (10,092 mg/dL) suggesting acute pancreatitis were also found
      on chemical analysis. The diagnosis of acute pancreatitis was confirmed by
      computed tomography scan. Treatment with continuous intravenous insulin--glucose,
      cessation of oral intake, and nasogastric decompression--dramatically decreased
      the triglyceride levels to 608 mg/dL within five days. She was discharged as
      symptom free with strict dietary intervention after 10 days. Intravenous insulin
      is a low-cost and effective alternative treatment in hypertriglyceridemia-induced
      pancreatitis during pregnancy. To our knowledge, such a high triglyceride level
      has not previously been reported in pregnancy.

PMID- 16623083
TI  - The need for logical application-based extensions in sickle cell disease research
      findings to changing lives in the ethnic context.

PMID- 16623084
TI  - Malaria vector control and personal protection.
AB  - Malaria transmission rates and risks can be greatly reduced by vector control,
      mitigating high malaria incidence and prevalence rates. Methods and strategies
      for malaria vector control (MVC) have been well documented by WHO, although its
      implementation varies widely. Technical guidelines for MVC strategies and
      materials are readily available, but the status and role of MVC have not been
      reviewed and redefined in terms of programme management and resource allocation.
      There are huge changes since November 1993 when the last WHO Study Group reviewed
      vector control for malaria and other mosquito-borne diseases, following the 1992
      adoption of the Global Malaria Control Strategy. Operationally, with reform of
      the health sector in many countries, the centrally managed and vertically
      structured malaria control programme (MCP) has been superseded by a community
      based and decentralized one. This poses challenges for effective implementation
      of MVC strategies. Therefore it became evident that the role of vector control in
      malaria control needs to be reconsidered to develop a strategic framework for MVC
      implementation by national malaria control programmes and other partners. This
      report of a WHO Study Group on Malaria Vector Control and Personal Protection
      reviewed the current vector control strategies and their effectiveness in various
      operational and eco-epidemiological settings, and identified challenges for
      implementation in different health systems. An outline strategic framework for
      strengthening malaria vector control implementation was developed. The process of
      deciding about which mosquito control method is appropriate in a given situation
      should be guided by an analysis of the level of malaria endemicity and vector
      bionomics, the eco-epidemiological setting, the health management system and an
      estimate of the programme sustainability. This report also provides a basis for
      the development of a strategic framework for strengthening malaria vector control
      implementation.

PMID- 16623085
TI  - [Human subsistence strategy in Neolithic times: an isotopic analysis of Bavarian
      skeletal findings].
AB  - Originating from the Near East, the Neolithic lifestyle will reach Southeast
      Europe in its fully developed form in the course of the 7th millennium cal. BC.
      In the region of today's Bavaria this lifestyle can be evidenced from the middle
      of the 6th millennium cal. BC onwards. Stable isotope analyses of carbon and
      nitrogen in bone collagen, and of carbon and oxygen in the bone's structural
      carbonate of human skeletons from burial sites dated to the Linear Pottery
      Culture, the middle Neolithic, the Corded Ware and the Bell Beaker Culture
      revealed differences in the dietary behaviour between 5500 until 3000 BC, and
      between 3000 until 2000 BC, respectively. In late Neolithic times, meat
      procurement appears improved and the dietary spectrum as such broadened,
      evidencing a more secured and increasingly flexible subsistence strategy. Oxygen
      isotope ratios of the structural carbonate proved to be reliable climatic
      indicators and may be helpful in the dating of archaeological sites.

PMID- 16623086
TI  - A new method for the automated age-at-death evaluation by tooth-cementum
      annulation (TCA).
AB  - A valid age at death estimation is required in historical and also forensic
      anthropology. Tooth cementum annulation (TCA) is a method for age at death
      estimation of adult individuals. The method is based on light microscope images
      taken from tooth-root cross sections. The age is then estimated by manually
      counting the cementum incremental lines and adding this to the chronological age
      at the assumed point of tooth eruption. Manual line counting, however, is time
      consuming, potentially subjective and the number of individual counts is
      insufficient for statistical evaluations. Software developed for the automated
      evaluation of TCA images, that uses Fourier analysis and algorithms for image
      analysis and pattern recognition is presented here. It involves "line-by-line"
      scanning and the counting of gray scale peaks within a selected region-of
      interest (ROI). Each scanning process of a particular ROI yields up to 400 counts
      that are subsequently statistically evaluated. This simple and time saving
      program seeks to substitute manual counting and supply consistent and
      reproducible results as well as reduce the demand of human error by eliminating
      unavoidable factors such as subjectivity and fatigue.

PMID- 16623087
TI  - Sequence of deltaF508 CFTR allele identified at present is lacking in medieval
      specimens from Central Poland. Preliminary results.
AB  - deltaF508 is the most common (70%) among over 1000 mutations of the gene encoding
      ATP-regulated chloride channel, namely CFTR--cystic fibrosis transmembrane
      regulator. The time which passed from the calculated mutation event was
      anticipated on the basis of the frequency of contemporary haplotypes, but not on
      its direct identification. The presence of three base pairs deletion in the
      ancient DNA (aDNA) isolated from skeletal remains of the Middle Ages origin was
      investigated. Teeth excavated in the area of three sites located in Central
      Poland were processed for a DNA. 6 out of 82 samples did not produce amplificable
      fragments of DNA. Although the number of specimens analyzed was sufficient to
      confirm the presence of the rare mutation, the deltaF508 CFTR sequence was not
      found in the remains of individuals living back 35 - 45 generations. The absence
      of the mutated allele in the particular geographic region cannot state for the
      status of mutated allele throughout the country, especially at times when
      migrations were limited and movements of people were more area restricted than at
      present days.

PMID- 16623088
TI  - Blood group and serum protein polymorphisms in a population group of Moldavians.
AB  - The distribution of the alleles and haplotypes for blood groups A1A2B0, MNSs,
      RHESUS, P1, KELL-CELLANO and biochemical markers of the alleles of loci AMY2,
      HPA, GC, C3, TF, BF, CP, PI (including subtypes) were studied in 125 Moldavian
      individuals from Karahasani settlement, Stefan-Voda District, Republic of
      Moldavia. The results show that the gene pool of Moldavians is similar to those
      of Southeastern European populations.

PMID- 16623089
TI  - Population variation in the incidence of the medial (hamate) facet of the carpal
      bone lunate.
AB  - Studies on the wrist joint have shown two types of the carpal bone lunate. In
      type II lunate there is a facet on the medial side of the lunate for articulation
      with the proximal pole of the hamate; such a facet is absent in type I lunate.
      Type II lunates have different kinematics, are more prone to clinically relevant
      degenerative changes in the hamato-lunate joint and are an uncommon cause of
      ulnar-sided wrist pain. Ninety plain radiographs showing postero-anterior views
      of the wrist (52 right and 38 left wrists) were studied in a population of Malays
      from Malaysia (mean age 48 years; age range 23 to 67 years) to determine the
      incidence of type I and type II lunates. Our findings were compared with those in
      other reports in the literature. In Malays, only 24 wrists (26.7%) showed a type
      II lunate compared to a reported incidence of 50% or more in populations from the
      Western world. Such a low incidence of type II lunate has not been reported
      before and may represent a genetic variation in Malays. Consequently,
      osteoarthritis of the hamate or lunate may play a less significant role in
      causing ulnar-sided wrist pain in Malays. In conclusion, the prevalence of type
      II lunate might vary in different population groups and further studies could be
      necessary to confirm this observation.

PMID- 16623090
TI  - [Are there sex differences in the prevalence of overweight and adiposity in
      elementary school children in Austria].
AB  - Based on the data of 203 male and 179 female schoolchildren from Eastern Austria
      (Burgenland), aged between 6 and 10 years, sex typical differences in body
      composition (absolute and relative body fat, lean body mass) and weight status
      were analyzed. Body composition analyses were carried out by means of BIA method,
      weight status was estimated using BMI percentiles (BMI > 90th percentile defined
      overweight, BMI > 97th percentile defined obesity). Statistically significant sex
      differences were found for all body composition parameters, girls exhibited a
      significantly higher amount of absolute and relative body fat, whereas their male
      counterparts exhibited a significantly higher amount of lean body mass. Regarding
      weight status, no statistically significant sex differences were observable,
      however, a higher amount of girls could be classified as overweight or obese.
      Evolutionary and sociocultural explanations for these observations are discussed.

PMID- 16623091
TI  - Age and sex variation of body mass index and waist circumference among the Santal
      children of Jharkhand, India.
AB  - Central body fat (CBF) as measured by waist circumference (WC) etc. has now been
      considered as risk factor for chronic disease, disability, and death. It has been
      assumed that one's characteristic level of body fat, as measured by body mass
      index (BMI), and CBF unfolds during the normal course of growth and development.
      However, studies of the development of CBF show relatively weak consistency in
      comparison to body fat. But to the best of our knowledge, no study in this aspect
      has been undertaken on any Indian population to study the effect of age and sex
      on body fat and CBF during development. In view of the above consideration, the
      present work has been undertaken among 179 Santal (a tribal population) children
      (Boys = 107, Girls = 72) of the Galudih area in East Singbhum, Jharkhand, India.
      Anthropometric measurements of height, weight, and circumference of waist were
      taken from each subject using standard procedure. The mean ages of boys and girls
      were 10.94 years and 9.48 years, respectively. The mean BMI for boys and girls
      were 14.48 kg/m2 and 13.78 kg/m2 Percent of variance explained by age was much
      greater for BMI (> 50%) as compared to WC (7-10%) in both sexes. Two way ANOVA
      showed that BMI had a significant (p < 0.05) effect of age and not of sex,
      whereas age-sex interaction had a significant impact on WC. The results of the
      present cross-sectional study indicated that during growth and development
      unfolding of CBF and BMI is independent of one another. Different set(s) of
      gene(s), onset of growth hormones during the normal development or their
      interaction could have been considered for this differentiation.

PMID- 16623092
TI  - Discriminant analysis by anthropometric measures in elderly Bengalee Hindus of
      Calcutta, India.
AB  - Although a sizeable proportion of India's population is elderly (55 years and
      above), virtually no information exists on how well anthropometric measures could
      be utilized to correct age group size in elderly individuals. The present
      investigation was aimed to study how good anthropometric measures could be
      manoeuvre for corrected group size in the elderly Bengalee Hindu population of
      Calcutta, India. A cross-sectional study was undertaken among 410 elderly (55
      years and above) Bengalee Hindu individuals (men = 210, women = 200) utilizing
      various anthropometric measures, namely height, weight, body mass index (BMI),
      mid upper arm circumference (MUAC) and triceps skinfold. A discriminant analysis
      was then undertaken separately for men and women using the above mentioned
      anthropometric measures. The results revealed that overall 77.1% for men and
      78.6% for women of all cases were correctly classified. No individuals were
      misclassified in the predicted groups III and I for both the sexes. The most
      discriminating variable for the groups was triceps skinfold in both sexes. These
      results provided evidence that the anthropometric characteristics of group III
      and I were very different from each other with those belonging to group II having
      intermediate characteristics.

PMID- 16623093
TI  - [The Swiss archaeologist Otto Hauser. His skeletal findings and hypothesis on the
      evolution of man and his extensive activities in the development of prehistorical
      research and evolution].
AB  - New investigations on Otto Hauser's skeleton findings and the excavations of this
      Swiss citizen in Southwest France from 1906 until 1914 placed the activities of
      this archaeologist again in the focus of scientific and public interest. This
      paper describes life and oeuvre of Otto Hauser and discusses the importance of
      the skeletons found by him and Hermann Klaatsch as well as the consequences of
      their discovery. The efforts of Otto Hauser to publish his discoveries, to
      present and spread his view concerning the evolution of man were remarkably
      manifold as well as the parallels between ancient man and contemporary ethnic
      groups living on a low technological level drawn by him and to wake and to
      promote the interest in prehistory. Many books, brochures, articles and public
      lectures contributed to this intention as well as co-operation with local
      historians and scientists of other disciplines, and also many films, teaching and
      illustrative materials. The scientific collection of the authors of this article
      comprises more than 6,500 written documents and photos.

PMID- 16623094
TI  - [The case of rofecoxib(Vioxx)-what do we learn from this case].

PMID- 16623095
TI  - [Support system for the relatives of suicides victims].

PMID- 16623096
TI  - [Gastric ulcer, helicobacter infections and chronic gastritis].

PMID- 16623097
TI  - [Physician practice patterns and hand hygiene].

PMID- 16623098
TI  - [Immediate complications of in vitro fertilization].

PMID- 16623099
TI  - [A fruit fly (Drosophila melanogaster) as a model organism for studies of brain
      diseases].

PMID- 16623100
TI  - [The use of anagrelide to treat thrombocytosis in connection with the chronic
      myeloproliferative disease].

PMID- 16623101
TI  - [The care of obstructive bronchitis].

PMID- 16623102
TI  - [Endocarditis caused by Gemella bacteria infection].

PMID- 16623103
TI  - [Weight loss and nausea during pregnancy].

PMID- 16623104
TI  - [Update on current care guidelines. Prolonged epileptic attack].

PMID- 16623105
TI  - [Importance for pH control of osteoclasts in bone resorption].

PMID- 16623106
TI  - [How should the care of dermatological diseases be developed?].

PMID- 16623107
TI  - [Abortions among university students have not been increasing].

PMID- 16623108
TI  - [Heart and kidneys].
AB  - During last fifty years several investigations were performed enabling detection
      and description of close relationships between kidneys and heart. It is dealing
      both with connections important for maintenance of homeostasis and with
      pathological disturbances. On the other hand there are no doubts that chronic
      kidney diseases, and especially their chronic failure, are connected with
      development of deep cardio-vascular changes. This interrelationship is becoming
      more clear when similiarities between factors causing progress of renal failure
      and development of cardio-vascular changes on the othe hand are concluded. So the
      main important issue is early prevention and after recognition of their existence
      early specific therapy.

PMID- 16623109
TI  - [Uraemic toxins and cardiovascular diseases].
AB  - The uremic syndrome is the result of the retention of solutes, which under normal
      conditions are excreted by the healthy kidneys into the urine. The most practical
      classification of uremic toxins is based on their physicochemical characteristics
      that influence their dialytic removal, in (a) small water soluble compounds, (b)
      the larger "middle molecules," and (c) the protein bound compounds. Most small
      water soluble compounds are not very toxic and the toxic ones often show a
      kinetic behavior that is different from that of urea. The incidence of vascular
      disease and the morbidity and mortality related to it are extremely high in the
      population of uremic patients. A large proportion of uremic patients suffer from
      inflammation. Most often, the uremic solutes that play a role in inflammation and
      cardio-vascular complications are middle molecules and/or protein bound. Protein
      bound toxins inhibit several biochemical functions. High concentrations of
      cytokines with an immune activating potential are present in the plasma of uremic
      patients.

PMID- 16623110
TI  - [Arterial stiffness--pathophysiological significance and practical aspects of
      assessment].
AB  - Arterial stiffness is a dynamic property which depends on structure and function
      of arteries. Arterial stiffness progresses with age and it is an important factor
      leading to increase of systolic and pulse pressure and decrease in diastolic
      blood pressure. Increased arterial stiffness was also found in hypertension,
      chronic renal failure and diabetes. Arterial stiffness is an independent
      prognostic factor of mortality in hypertension and end-stage renal disease.
      Arterial stiffening leads to cardiovascular complications such as left
      ventricular hypertrophy. Many methods to assess different aspects of arterial
      stiffness: systemic, regional and local were developed. Various indicies of
      arterial stiffness were defined and are used in clinical investigations. Arterial
      stiffness is a dynamic parameter. Decrease in blood pressure leads to decrease of
      arterial stiffness. Many authors suggest, that angiotensin converting enzyme
      inhibitors may exert favourable effect, irrespective of blood pressure. Arterial
      stiffness assessment may become a cardiovascular risk parameter and a therapeutic
      goal.

PMID- 16623111
TI  - [Microalbuminuria--underestimated cardiovascular risk factor].
AB  - The term microalbuminuria stands for an increased urinary excretion of albumin
      undetectable by routine methods for determination of proteinuria.
      Microalbuminuria is found in a substantial proportion of patients with diabetes,
      arterial hypertension and in the elderly. New data has provided strong evidence
      that albuminuria not only indicates early glomerular damage but also widespread
      endothelial dysfunction, early atherogenesis and increased cardiovascular and
      cerebrovascular risk. It has been shown that angiotensin converting enzyme
      inhibitors have a potential to decrease urinary albumin excretion, which confirms
      their well-established nephro- and vasoprotective action.

PMID- 16623112
TI  - [Anemia in kidney diseases as a cardiovascular risk factor].
AB  - Cardiovascular mortality is increased in chronic kidney diseases. Patients'
      survival correlates with hemoglobin concentration. Anemia significantly affects
      cardiovascular system, especially the heart. Heart failure, anemia and chronic
      renal failure are mutually related. Recently, cardio-renal-anemia syndrome (CRAS)
      was defined. Iron replacement and EPO treatment can break the pathogenetic circle
      of events leading to heart failure. Increased hemoglobin concentration can also
      induce a positive impact on renal function. Early diagnosis and correction of
      anemia has a substantial role in prophylaxis of left ventricular hypertrophy in
      patients with chronic renal insufficiency.

PMID- 16623113
TI  - [Can human recombinant erythropoietin (rHuEPO) be considered as cardiological
      medicine?].
AB  - Recombinant human erythropoietin (rHuEPO) is a hormone essential for normal
      erythropoiesis. The rHuEPO receptor is distributed in the cardiovascular system
      predominantly in endothelial cells and cardiomyocytes. RHuEPO has potentially
      beneficial effects on cardiovascular system, including anti-apoptic, mitogenic
      and angiogenic activity. On the other hand rHuEPO improves anemia observed in
      some patients with heart failure. Direct cardiac activity of rHuEPO and indirect
      influence on anemia suggest that rHuEPO therapy is safe and useful in chronic
      heart failure patients and other cardiovascular settings.

PMID- 16623115
TI  - [Principles of rational cooperation of general practitioners and other
      specialists with nephrologist].
AB  - The paper presents general principles of rational cooperation of general
      practitioners and other specialists with nephrologist dedicate special attention
      concerning the slowing progression of renal failure and beneficts for patients as
      a result of early referral to nephrologist. The management of patients with
      chronic renal failure in the predialysis period and their preparation for renal
      replacement therapy was also described.

PMID- 16623114
TI  - [Progress in clarification of the pathogenesis of primary arterial hypertension].
AB  - The results of the studies performed during the last years have supplied several
      new elements to the knowledge about pathogenesis of primary arterial
      hypertension. The monogenic forms of arterial hypertension and syndromes
      associated with low blood pressure were characterized. The negative regulators of
      sodium transport in the kidneys, with potential importance for the clarification
      of mechanism causing sodium sensitivity of blood pressure, were discovered. It
      was demonstrated that patients with primary hypertension had inherited lower
      number of nephrons in the kidneys, demonstrating compensatory hypertrophy when
      compared with normotensive persons. There is more and more proofs that in many
      cases the basis of arterial hypertension, contemporary diagnosed as primary
      hypertension, is genetically determined impairment of kidney function or
      inherited disturbances of kidney structure.

PMID- 16623116
TI  - [Renal failure in patients after acute coronary syndrome--does it change the
      standards? From theory to practice].
AB  - Standards for secondary prevention in patients after acute coronary syndromes
      have been recently published by the European Society of Cardiology. They do not
      differ between patients without or with renal failure, but it may be suggested
      that the later group deserves special attention and more aggressive treatment.
      Both after myocardial infarction and unstable angina, practically all patients
      are supposed to receive antiplatelet therapy, statins, beta-blockers and
      angiotensin-converting enzyme (ACE) inhibitors. They also are submitted to
      intensive coronary risk factor modifications. In recently undertaken Polish
      registry study of secondary prevention in acute myocardial infarction/unstable
      angina survivors and post-revascularization patients (STOK--Standard Terapii i
      Opieki Kardiologicznej trial) over 31,000 records of individual patients
      discharged from internal disease or cardiologic wards in Poland in 2002 were
      gathered. When records of 2,780 patients with concomitant elevated serum
      creatinine were compared with data of 28,585 patients with normal renal function,
      some interesting conclusions were drawn. Firstly, the group of patients with
      suspected renal dysfunction was characterized with more often recognized:
      diabetes, heart failure and peripheral vessel disease. Secondly paradoxically-
      they were less often prescribed with antiplatelet drugs, statins, beta-blockers
      and ACE inhibitors. Thus theory do not translate into practice.

PMID- 16623117
TI  - [Beta-adrenolytics in heart failure--are they all really equal?].
AB  - The Carvedilol or Metoprolol European Trial (COMET) found that in patients with
      heart failure, survival appears to be better with carvedilol than with immediate
      release metoprolol. Whether the target doses used were equivalent (carvedilol 25
      mg twice daily; mean daily dose 85 mg vs metoprolol 50 mg twice daily; mean daily
      dose 42 mg) has been debated, but the COMET trial shows that drugs in the same
      class do not necessarily have the same effects. Given the overwhelming evidence
      of the benefit of carvedilol, metoprolol, and bisoprolol in patients with heart
      failure, we should all work to increase the use of these drugs in appropriate
      doses. Carvedilol and metoprolol both decrease mortality in heart failure,
      although their pharmacological profiles differ a lot. It is not clear whether the
      ancillary properties, which carvedilol has, but metoprolol does not assess,
      contribute to its beneficial effect. In COMET trial all-cause mortality was less
      in the carvedilol than the metoprolol group, indicating that at trial doses,
      carvedilol has a mortality benefit over metoprolol. However, the beta(1)
      adrenoceptor blocking activity of metoprolol (assessed by a decrease in heart
      rate) was slightly less than with carvedilol in COMET and less than that observed
      in previous mortality studies with metoprolol, suggesting that the use of
      metoprolol was not optimal in COMET. Nevertheless, we may conclude all beta
      adrenolytics used in heart failure are not really equal as far as evidence-based
      medicine data are currently concerned. The article summarizes some new
      investigations into ancillary properties of carvedilol which may decide of its
      special position among beta-adrenolytices used in heart failure.

PMID- 16623118
TI  - [Hypertension in haemodialysis and peritoneal dialysis patients].
AB  - Hypertension occurs in many reports in 80-100% ESRD patients and is the most
      important risk factor of cardiovascular morbidity and mortality. Successful
      therapy of hypertension depends on many factors including specific,
      pathophysiological mechanisms, ability of optimal renal replacement therapy and
      pharmacotherapy in the circumstances of different drugs pharmacokinetics. The
      review is aimed on recent reports concerning the role of optimal dialysis
      especially dose, duration of the procedure and some pharmacological aspects of
      blood pressure control in ESRD patients.

PMID- 16623119
TI  - [Cardiovascular risk factors and their modification after renal transplantation].
AB  - Cardiovascular disease is the leading cause of death in renal transplant
      recipients. Death with a functioning graft is the main cause of graft failure.
      Risk factors for cardiovascular complications and modification of methods are
      discussed.

PMID- 16623120
TI  - [Statins in patients with renal failure--the current therapeutic status].
AB  - Statins are the most frequently used lipid-lowering drugs in all cardiovascular
      disease. It has been postulated that also patients with renal failure and end
      stage renal disease (ESRD) may benefit from statin therapy. Moreover, statins may
      exhibit additional inhibitory effects on the atherogenesis, such as a modulation
      of the immune system as triggered by oxidatively modified LDL and a reduction of
      the inflammatory marker C-reactive protein (CRP). Statins reduce inflammation,
      cell proliferation, which leads to a reduction in cellular damage. Those effects
      are probably independent of cholesterol levels. Limited data suggest that HMG-CoA
      reductase inhibitors (statins) may slow loss of renal function in individuals
      with chronic renal insufficiency. It is concluded on the basis of the CARE trial
      that pravastatin may slow renal function loss in individuals with moderate to
      severe kidney disease, especially those with proteinuria. Similar data were
      obtained from recently published HPS trial with simvastatin. These findings
      require confirmation by a large randomized trial conducted specifically in people
      with chronic renal insufficiency. Statins vary in their pharmacological profiles,
      leading to distinct levels of systemic exposure and capacities to penetrate
      skeletal myocytes. Pharmacokinetic interactions with certain agents increase the
      likelihood of statin-induced myopathy and, in exceedingly rare instances,
      potentially fatal rhabdomyolysis with myoglobinuria and renal failure, therefore
      two statins have been suggested for renal failure patients. These are the ones
      that are not metabolised by the cytochrome P450 3A4 system--fluvastatin and
      pravastatin. The article summarizes the current therapeutic status of statin use
      in renal failure patients.

PMID- 16623121
TI  - [Percutaneous coronary interventions in patients with ischemic heart disease and
      chronic renal failure].
AB  - Patients with chronic renal failure (CRF) consist of about 10% of all patients
      with ischemic heart disease (IHD) undergoing percutaneous coronary interventions
      (PCI). These patients have a higher rate of in-hospital and long-term major
      adverse cardiac events. Coronary stents improved prognosis in CRF patients,
      however long-term survival is still poor. Coronary artery bypass graft (CABG)
      surgery is an alternative modality of treatment, with better long-term prognosis
      but at the cost of higher in-hospital mortality. CABG surgery probably should be
      preferred in patients with CRF and multivessel coronary artery disease, left main
      stenosis or diabetes. The influence of drug-eluting stents on survival in
      patients with CRF is unknown.

PMID- 16623122
TI  - [Nephrotoxic action of contrast media].
AB  - Contrast induced nephrotoxity [CIN] is a common form of hospital-acquire renal
      failure. Prevention can decrease the need for dialysis, morbility, and reduce
      health care costs. All patiens receiving iodine-contrast medium should be
      assessed for risk of developing CIN. Prophylaxis can reduce CIN. Patients at risk
      requiring injection of contrast medium [CM] with important clinical indications
      should receive a small dose of non-ionic iso-osmolar dimeric or non-ionic low
      osmolar monomeric CM and hydratation with normal saline before and after
      exposure. This brings the best protection with the fewest adverse effects.

PMID- 16623123
TI  - [Nephrology of love].
AB  - The article presents different aspects of the connection between human heart and
      kidneys. This connection is evident in the symbolism of the Old Testament of the
      Bible, organ donation as the manifestation of the love of our neighbor,
      endocrinological and sexual dysfunction, and finally in searching for biological
      determinants of finer feelings. In the Old Testament tradition kidneys were
      thought to be human spirit's dwelling. Moreover, the simultaneous studying of
      kidneys and heart meant profound understanding of the matter. Nowadays, it is
      also possible to find the Biblical love of our neighbor, for instance among
      kidney donors. What is more, every nephrologist should treat his patients with
      love and dedication, which makes it easier for him to understand their problems,
      especially these concerning sexual dysfunction. Sexual dysfunction occurs among
      men and women equally and specialists, apart from using many different methods,
      have to deal with the consequences of renal failure mainly by means of
      transplantation.

PMID- 16623124
TI  - We effect rules for the dentists of Tennessee.

PMID- 16623125
TI  - State of the association address.

PMID- 16623127
TI  - Advising young dental editors.

PMID- 16623126
TI  - Open leadership.

PMID- 16623128
TI  - Distributive justice in dentistry.

PMID- 16623129
TI  - Today's New dentists face professional challenges and opportunities.
AB  - The substantial debt load of new dentists is part of the recent trend toward
      beginning practice as an associate, in a postdoctoral general dentistry program,
      or in the military. Other reasons include an opportunity to build clinical speed,
      learning practice management skills, and earning a guaranteed income. While
      today's new dentists value the same goals of quality, service, and autonomy that
      motivate established practitioners, they bring new dimensions to the profession.
      Diversity and a desire for a balanced lifestyle (among both men and women) affect
      practice decisions and participation in organized dentistry. The new dentist will
      look for flexibility and responsiveness to personal and social challenges.

PMID- 16623130
TI  - Reframing diversity: younq dentists and the numbers game.
AB  - Diversity is not the same thing as equality, although it creates pressure in that
      direction. As America becomes more diverse, we would like to see greater progress
      in access to education and equitable entry into the profession. The new dentist
      is increasingly both young and a member of a minority group. Foundations, such as
      Kellogg, Robert Wood Johnson, and the California Endowment, and the Hispanic, the
      National, and other ethnically affiliated dental associations and the American
      Association of Women Dentists are becoming a voice to convert diversity into
      equality.

PMID- 16623131
TI  - New dentist shows commitment to community and profession.
AB  - In 2005, Dr. Jose Peralez won the ADA's Golden Apple Award for New Dentist
      Leadership. He is a second-career native of the Rio Grande Valley who returned
      after his 1995 graduation from dental school to serve the community he grew up
      in. Dr. Peralez helped to purchase, manage, and staff a mobile clinic, create a
      voucher program administered through school nurses, and engage legislators in
      issues of oral health care for the underserved. He believes that "habits of
      involvement" are cross generational and contagious.

PMID- 16623132
TI  - Mentor says learning is a two-way street.
AB  - This year's winner of the ADA award for Individual Achievement in Mentoring, Dr.
      Ronald Stifter explains how opportunities exist for established dentists to
      mentor students and young practitioners. In a changing professional world where
      competition, debt, and diversity have grown, the guidance of a mature dentist is
      a valuable way to invest in the future of the profession.

PMID- 16623133
TI  - Clinical licensure exams: the unruly gatekeepers.
AB  - A dental student approaching graduation reflects on concerns over initial
      licensure examinations. Among the issues that have been recognized but remain
      unaddressed are ethical treatment of live patients, unfair treatment of
      candidates, excellent reliability among examiners on any single case but poor
      consistency across testing, lack of validity, and no evidence of protecting the
      public. The licensure system would be improved by paying attention to issues of
      mobility and continued competence.

PMID- 16623134
TI  - Visions and viewpoints: promises and reality.
AB  - The immediate past chair of the ADA Council on Ethics, Bylaws and Judicial
      Affairs, who is also an attorney, explains why, after a thirty-year absence, he
      went back to treating Medicaid patients. It is easy to identify the social,
      political, bureaucratic, and financial shortcomings of our imperfect system. But
      how else, besides participating, can one educate patients so the dentist and the
      patient can both accept responsibility? How else can the profession make a
      difference except one patient at a time?

PMID- 16623135
TI  - What does the fact of advertising convey to patients?

PMID- 16623136
TI  - Changing perspectives on dental advertising.

PMID- 16623137
TI  - Generations.
AB  - Groups naturally promote their strengths and prefer values and rules that give
      them an identity and an advantage. This shows up as generational tensions across
      cohorts who share common experiences, including common elders. Dramatic cultural
      events in America since 1925 can help create an understanding of the differing
      value structures of the Silents, the Boomers, Gen Xers, and the Millennials.
      Differences in how these generations see motivation and values, fundamental
      reality, relations with others, and work are presented, as are some applications
      of these differences to the dental profession.

PMID- 16623138
TI  - 20 years of carrying out a calling.

PMID- 16623139
TI  - Midwifery model of care--phase II: midwife lessons.

PMID- 16623140
TI  - Midwives, mothers and mothers-in-law.

PMID- 16623141
TI  - Mothers: birth helpers, bosses or intruders?

PMID- 16623142
TI  - Vaginal births after C-section are not necessarily riskier in a birth center than
      in the hospital.
AB  - Recent research concluded that VBACs are riskier in a birth center than in the
      hospital. This conclusion is only true if the woman is sure she will not have any
      more pregnancies and if she does not suffer from "Fear of Hospitals." Since
      childbirth centers offered a VBAC rate of 87%, whereas US hospitals currently
      offer a VBAC rate of less than 10%, the woman has a much higher risk of a repeat
      cesarean if she delivers in hospital, which increases her risk on subsequent
      pregnancies.

PMID- 16623143
TI  - Prenatal diagnosis--technological triumph or Pandora's box?

PMID- 16623144
TI  - A road home.

PMID- 16623145
TI  - Sexual abuse and pregnancy--a homeopath's perspective.

PMID- 16623146
TI  - Sage-femme.

PMID- 16623147
TI  - The anatomy of a miracle.

PMID- 16623148
TI  - Elizabeth Davis: An interview with Heather Long.

PMID- 16623149
TI  - At home in birth.

PMID- 16623150
TI  - HIV and breastfeeding: What we do and do not know in 2005.

PMID- 16623151
TI  - The business of midwifery: documentation for success III--homebirth.

PMID- 16623152
TI  - Miracle birth.

PMID- 16623153
TI  - Working at the CURE Hospital in Kabul, Afghanistan.

PMID- 16623154
TI  - A Mexican adventure.

PMID- 16623155
TI  - Red Internacional de Parteras Independientes (RIPI).

PMID- 16623156
TI  - Guatemala: Has the time come for a national midwifery certification program?

PMID- 16623157
TI  - Anciona Juarez Arrosco.

PMID- 16623158
TI  - I was blessed: A lay midwife's story.

PMID- 16623159
TI  - Urology's future: what do we see in our silicone balls?

PMID- 16623160
TI  - Radiofrequency ablation (VNUS closure) does not cause neo-vascularisation at the
      groin at one year: results of a case controlled study.
AB  - BACKGROUND: Despite adequate training in the surgical treatment of varicose
      veins, recurrence continues to be a problem and a burden to the vascular
      services. A major cause of recurrence is reported to be neo-vascularisation at
      the sapheno-femoral junction (SFJ). The aim of this study was to compare the
      incidence of neo-vascularisation at the SFJ following radiofrequency ablation
      (RFA) and open high saphenous tie and stripping (HSTS). MATERIALS AND METHODS:
      Fifty-one patients (55 legs) underwent standardised HSTS as part of a prospective
      study. These were compared with an age (range 28-83, mean 54.4) and sex
      (male:female 31:20) matched group of patients treated during the same time
      period, by the same consultant vascular surgeon, using RFA (VNUS closure). Each
      patient had a pre-operative duplex scan to confirm SFJ reflux, a one-week scan to
      confirm successful surgery and a one-year post-operative scan to assess neo
      vascularisation. The same vascular technologist performed all scans. Neo
      vascularisation was identified by the presence of refluxing tortuous vessels
      arising from the area of the SFJ. RESULTS AND CONCLUSION: Six of 55 (11%) legs in
      the open surgery group showed clear evidence of tortuous refluxing veins related
      to the SFJ. None of the 55 in the RFA group showed any neo-vascularisation at the
      SFJ (Fischer exact test P = 0.028). Further randomised controlled trials are
      necessary to confirm these observations.

PMID- 16623161
TI  - Histological examination of circular stapled 'doughnuts': questionable routine
      practice?
AB  - BACKGROUND: Left-sided colonic resections are often anastomosed by the use of the
      circular stapling gun. Most surgeons routinely submit the resulting set of
      'doughnuts' for histological examination. AIM: The aim of this study is to
      question the need for this practice by providing our own experience of the impact
      of 'doughnut' submission on patient management. PATIENTS AND METHODS: Patients
      who had undergone a stapled anastomosis for colorectal cancer resection (1998
      2004) were identified from the department cancer database and clinical records
      and histopathological reports were reviewed for all cases. RESULTS: From a
      consecutive series of 100 sets of doughnuts only two showed histological
      abnormality (inflammatory change and a metaplastic polyp). Three patients had
      local recurrence over the follow-up period: 12, 14 and 36 months after surgery.
      Histological review of the 'doughnuts' in these patients did not show any
      abnormality. None of the above findings had any influence on subsequent
      management. CONCLUSION: Histological examination of the 'doughnuts' has a
      considerable impact in terms of time and resource use. This study has shown no
      benefit in performing routine histological examination of the 'doughnuts'.

PMID- 16623162
TI  - Value of biopsy in the assessment of a retroperitoneal mass.
AB  - AIMS: A retroperitoneal mass arising outside a specific organ usually gives rise
      to diagnostic uncertainty. Because of this, many clinicians request a
      radiologically guided biopsy. The aim of this study was to compare clinical and
      radiologic assessment with and without biopsy in patients undergoing surgical
      resection of a large abdominal mass. METHODS: All patients undergoing resection
      of a large retroperitoneal mass under the care of one surgeon between 1994 and
      2004 were included in this study. RESULTS: One hundred and twenty-one patients
      underwent resection of a large retriperitoneal mass, of whom 84 had primary
      disease (median size 20cm, range 7cm-40cm). Thirty-six had clinical and
      radiologic assessment with biopsy while 48 had no biopsy. In the biopsy group
      four patients had a false negative result while two had a false positive result
      for a malignant tumour. Three patients had incorrect malignant histology on
      biopsy which led to an error in management in two. In addition, two adverse
      events related to biopsy were observed. One patient in the no biopsy group had an
      error in management. Sensitivity for diagnosis of a soft tissue tumour was 80.8%
      (95% CI 69.5%-92.1%) for clinical and radiologic assessment alone versus 91.6%
      (95% CI 82.6%-100%) when biopsy was added. CONCLUSIONS: Biopsy adds no value to
      clinical and radiologic assessment of the patient with a resectable large
      retroperitoneal mass.

PMID- 16623163
TI  - Screening of abdominal aortic aneurysms.

PMID- 16623164
TI  - The not-so-lazy-T: a modification of medial ectropion repair.
AB  - Medial involutional ectropion without excessive lateral canthal tendon laxity is
      often corrected using the lazy-T procedure. This procedure however carries a
      potential risk of canalicular damage, and locating the lower lid retractors can
      be difficult. We have developed a modification. Replacing the tarso-conjunctival
      diamond with a subconjuctival pocket posterior and inferior to the punctum, into
      which the lower lid retractors are advanced from the base of the wedge excision,
      which effectively ensures plication of the lower lid retractors while maintaining
      a straightforward procedure. The follow-up data on five procedures showed
      surgical and symptomatic success in all patients, without complications. These
      results confirm the efficacy of this modification of the lazy-T procedure in the
      correction of medial lower lid ectropion.

PMID- 16623165
TI  - The future of hip arthroplasty: a trainee's perspective.

PMID- 16623166
TI  - John Barclay (1758-1826) extra-mural teacher of anatomy in Edinburgh: Honorary
      Fellow of the Royal College of Surgeons of Edinburgh.
AB  - John Barclay (1758-1826) was one of the most distinguished, respected and
      enthusiastic teachers of anatomy in Edinburgh during the first decades of the
      19th century. He taught this subject in the extra-mural school from 1797 until
      1825. He initially studied divinity at St Andrews University, intending entering
      the Church. After acting as a minister of the Church for about 10 years and
      tutoring for most of these years, he decided to study medicine in Edinburgh, and
      was particularly attracted to anatomy. After he qualified with the MD degree, he
      proceeded to London where he attended the anatomical classes of Dr Marshall for
      about a year. On his return to Edinburgh he taught anatomy to a small class for
      three years in High School Yards. He then acquired a property at Number 10
      Surgeons' Square where he taught from 1800 until 1825, when he was forced to
      withdraw due to poor health. His lectures were meticulously prepared, and his
      illustrations clear and copious. In 1804, his class was recognised by the Royal
      College of Surgeons of Edinburgh as fulfilling their requirements for students
      who wished to take the College's examinations. During the winter sessions he
      taught anatomy, physiology and surgery, while in the summer sessions he taught
      comparative anatomy, a subject in which he was particularly interested. He was
      elected an Honorary Fellow of the Royal College of Surgeons of Edinburgh in 1821.
      His classes were taken over by his partner Robert Knox, at that time Conservator
      of the College's Museum.

PMID- 16623167
TI  - Partial hepatectomy is curative for the localized type of Caroli's disease: a
      case report and review of the literature.
AB  - The case of a 58-year-old woman who was diagnosed with the localized type of
      Caroli's disease is presented. This disease involves the whole of the left half
      of the liver. A left hepatectomy was followed by complete resolution of symptoms.
      The current article suggests that hepatic resection may be aggressively performed
      in selected patients with the localized form of Caroli's disease.

PMID- 16623168
TI  - Red herring: a rare cause of small bowel obstruction.
AB  - This is a case report of a 73-year-old man with a small bowel obstruction
      secondary to an incarcerated paracaecal hernia. His large right inguinal hernia,
      initially suspected as a potential source of obstruction, turned out to be a red
      herring. Congenital internal hernias are a very rare cause of bowel obstruction.
      In this report we review the literature and embryology behind these uncommon
      occurrences.

PMID- 16623169
TI  - Complex iliac and bilateral common femoral artery aneurysms: a novel hybrid
      procedure.
AB  - A 74-year-old man presented with a right common iliac artery aneurysm and
      bilateral common femoral artery aneurysms. These aneurysms were repaired by a
      hybrid procedure. A one-stage approach was chosen including an endovascular stent
      graft and femoro-iliaco-femoral Y-bypass grafting. The authors describe a novel
      combined open and endovascular approach to repair these complex aneurysms.

PMID- 16623170
TI  - Intraabdominal desmoid tumour presenting with perforation.
AB  - We present a rare case of a desmoid tumour presenting with perforation of the
      small bowel. Although desmoid is classified pathologically as a benign tumour,
      its infiltrative nature leads to a locally aggressive mass, which can invade
      surrounding structures and organs making surgical resection difficult. Some
      unresectable tumours show oestrogen receptor positive cells and can be managed
      with tamoxifen. The aetiology, investigation and management options are briefly
      described.

PMID- 16623171
TI  - Re: Hinduja K, Samuel R, Mitchell S. Problem-based learning: is anatomy a
      casualty? Surgeon 2005; 3 (2):84-87.

PMID- 16623172
TI  - Re: Hinduja K, Samuel R, Mitchell S. Problem-based learning: is anatomy a
      casualty? Surgeon 2005; 3 (2):84-87.

PMID- 16623173
TI  - Re: Hinduja K, Samuel R, Mitchell S. Problem-based learning: is anatomy a
      casualty? Surgeon 2005; 3 (2):84-87.

PMID- 16623174
TI  - Re: Spielmann PM, Oliver CW. The carpal bones: a basic test of medical
      students'and junior doctors' knowledge of anatomy. Surgeon 2005; 3 (4): 257-59.

PMID- 16623175
TI  - Re: Spielmann PM, Oliver CW. The carpal bones: a basic test of medical students'
      and junior doctors knowledge of anatomy. Surgeon 2005; 3(4): 257-59.

PMID- 16623176
TI  - Re: Hinduja K, Samuel R, Mitchell S. Problem based learning: is anatomy a
      casualty? Surgeon 2005; 3(4):84-87. Re: Spielmann PM, Oliver C W. The carpal
      bones: a basic test of medical students' and junior doctors knowledge of anatomy.
      Surgeon 2005; 3(4): 257-59.

PMID- 16623177
TI  - Re: Spielmann P M, Oliver C W. The carpal bones: a basic test of medical
      students' and junior doctors knowledge of anatomy.

PMID- 16623178
TI  - Systemic toxicity following ingestion of the chlorhexidine gluconate solution: a
      case report.
AB  - The purpose of this article is to discuss possible adverse effects and emergency
      treatments following the ingestion of chlorhexidine (CHX). In this case a dental
      student (age 25, male) accidentally swallowed one shot of 20% CHX solution, which
      is equal to 100 shots of the standard 0.2% CHX mouthwash. Clinical emergency
      treatment included: washing the oral cavity with 30 g of toothpaste, drinking 100
      ml of 5% (w/v) alginate syrup and ingestion of 5 g of cork. The following adverse
      effects were experienced: headache, euphoria, giddiness, blurred vision (duration
      = 12 h), stomachache, gastric lavage with demulcents (duration = 24 h) and
      complete loss of taste sensation (duration = 8 h), which recurred during the next
      48 h. No change in plasma aminotransferase level was seen. We used basic chemical
      information about the incompatibilities of CHX for clinical management of
      unintentional ingestion. It is known that CHX is a cation, and, therefore, first
      aid in case of intoxication with CHX involves using anionic materials.

PMID- 16623179
TI  - Root coverage in a class IV recession defect achieved by creeping attachment: a
      case report.
AB  - BACKGROUND AND OBJECTIVES: The amount of root coverage obtained after a graft
      procedure may be improved after the early phase of healing by a coronal
      displacement of the gingival attachment. The aim of this report is to present a
      clinical case of complete root coverage of a Miller's class IV recession achieved
      by creeping attachment subsequent to a laterally repositioned flap. METHODS: In
      1995, a 44-year-old male patient was referred for a root coverage graft on the
      upper right central incisor. Clinical examination revealed that the upper right
      central incisor had a recession of 7 mm. The defect was classified as class IV
      according to Miller's classification of marginal tissue recession. It was decided
      that root coverage would be attempted using a laterally repositioned flap from
      the upper right lateral incisor and upper right canine. Sutures were removed ten
      days after surgery. RESULTS: Four months after grafting, the amount of root
      coverage obtained was 4 mm. After an 8-year period, the previously denuded root
      surfaces were entirely covered by soft tissue. The marginal position of the
      gingiva appeared stable, the gingival tissue became firmly attached to the root
      surface and probing showed a shallow sulcular depth. CONCLUSION: Several
      interesting observations were made after 8 years. In conclusion, the most
      significant and interesting finding of this report is that the amount of
      interdental papilla and marginal gingival tissue covering donor and recipient
      areas improved with time, providing an excellent aesthetic appearance.

PMID- 16623180
TI  - Coronally positioned flap with subepithelial connective tissue graft for root
      coverage: various indications and flap designs.
AB  - Aesthetic concerns and functional abnormalities, such as dentin hypersensitivity,
      are often associated with gingival recession defects. Root coverage procedures
      aim to restore both gingival aesthetics and function in recession defects. The
      coronally positioned flap combined with the subepithelial connective tissue graft
      is one of the most widely used root coverage procedures. The present report
      illustrates four different indications where this procedure has been successfully
      employed. An isolated Miller class II recession defect associated with frenum
      pull, multiple adjacent Miller class I defects in the aesthetic zone, an isolated
      Miller class I defect associated with dentin hypersensitivity, and an isolated
      Miller class II defect on a retained deciduous tooth are the four diverse
      conditions treated by periodontal plastic surgery. Different approaches were used
      to create the coronally positioned flap. Treatment resulted in complete root
      coverage, resolution of hypersensitivity, and satisfaction of the patients'
      aesthetic concerns. An effective and predictable treatment modality, such as the
      coronally positioned flap combined with the subepithelial connective tissue
      graft, should be considered when treatment planning for gingival recession
      defects.

PMID- 16623181
TI  - Periodontal disease and diabetes metabolic control: a full-mouth disinfection
      approach.
AB  - Some studies demonstrated that local mechanical periodontal treatment and
      systemic antibiotics might improve the level of metabolic control in patients
      with diabetes. The aim of this clinical pilot trial was to evaluate if type 1
      diabetes patients with periodontitis will experience improvement in periodontal
      status and glycemic control after a full-mouth disinfection treatment. Ten adult
      patients with poor metabolic control (mean glycated hemoglobin (HbA1c) = 10.7 %)
      and periodontitis were included in the study. All patients received a full-mouth
      disinfection in 24 hours as described by Quirynen et al. (1995) at baseline and 6
      months later. The periodontal parameters included plaque index (PI), bleeding on
      probing, probing depth and clinical attachment loss. Metabolic control was
      measured by the serum level of HbA1c. All measurements were done at baseline and
      at 3, 6, 9 and 12 months. The results demonstrated a significantly lower PI, less
      bleeding on probing, reduction in probing depth and gain of clinical attachment
      at 3 months and 9 months of the study. Similarly, a significant reduction in the
      serum level of HbA1c was measured three months after full-mouth disinfection but
      disappeared 6 months later at the 6- and 12-month check points. We conclude that
      a full-mouth disinfection approach significantly improves periodontal status and
      metabolic control in type 1 diabetes patients with periodontitis. However, the
      results of our study imply that a full-mouth disinfection method has to be
      applied at least every 3 months to control periodontal status and glycemic
      control in type 1 diabetes patients. Further studies with greater numbers of
      diabetes patients are needed to confirm the long-term beneficial effects of a
      full-mouth disinfection approach on diabetic metabolic control.

PMID- 16623182
TI  - Proliferative verrucous leukoplakia and field cancerization: report of a case.
AB  - Proliferative verrucous leukoplakia (PVL) is a multi-focal oral pre-malignant
      lesion, proliferative in nature, with a tendency to recur despite adequate
      therapy, and a high rate of malignant transformation. The field cancerization
      phenomenon may explain the characteristic behaviour of PVL. A case of PVL is
      presented and the field cancerization concept is discussed.

PMID- 16623183
TI  - Payers need to streamline Part D turnaround time to head off potential regulatory
      changes.

PMID- 16623184
TI  - Senate, House Budget Committees pass budget resolutions.

PMID- 16623185
TI  - Achieving the millennium development goals in Africa: how realistic?

PMID- 16623186
TI  - The potential impact of community-based distribution programmes on contraceptive
      uptake in resource-poor settings: evidence from Ethiopia.
AB  - Community-based reproductive health services (CBRHS) have been in implementation
      in Ethiopia for over a decade. This paper assesses the impact of such programmes
      on contraceptive use. The data were obtained from the 2000 Ethiopian Demographic
      and Health Survey (DHS) and the 2003 Contraceptive Prevalence Survey (CPS). While
      the 2000 DHS contained a nationally representative random sample of women of
      reproductive age, the 2003 CPS focused on areas with active CBRHS programmes. The
      findings indicate that expanding the current CBRHS programme has the potential of
      doubling the current national contraceptive prevalence rate.

PMID- 16623187
TI  - Factors contributing to maternal mortality in north-central Nigeria: a seventeen
      year review.
AB  - Maternal mortality ratio in Nigeria is one of the highest in the world. This
      paper reports a facility based study in north-central Nigeria to determine the
      magnitude, trends, causes and characteristics of maternal deaths before and after
      the launch of the Safe Motherhood Initiative in Nigeria, with a view to
      suggesting strategic interventions to reduce these deaths. The records of all
      deliveries and case files of all women who died during pregnancy and childbirth
      between January 1, 1985 and December 31, 2001, in the maternity unit of Jos
      University Teaching Hospital, Jos, Nigeria, were reviewed. Data collected were
      analysed for socio-biological variables including age, booking status,
      educational level, parity, ethnic group, marital status, mode of delivery,
      duration of hospital stay before death occurred, cause (s) of maternal deaths.
      There were 38,768 deliveries and 267 maternal deaths during the period under
      review, giving a maternal mortality ratio (MMR) of 740/ 100,000 total deliveries.
      The trend fluctuated between 450 in 1990 and 1,010/100.000 deliveries in 1994.
      The mean age of maternal death was 26.4 (SD 8.1) years. The greatest risk of MMR
      was among young teenagers (> 15 years) and older women (< 40 years). Parity
      specific maternal mortality ratio was highest in the grand multiparous women.
      Unbooked as well as illiterate women were associated with very high maternal
      mortality ratio. The Hausa - Fulani ethnic group contributed the largest number
      (44%) by tribe to maternal mortality in our study. The major direct causes of
      deaths were haemorrhage (34.6%), sepsis (28.3%), eclampsia (23.6%) and unsafe
      abortion (9.6%). The most common indirect causes of death were hepatitis (18.6%),
      anaesthetic death (14.6%), anaemia in pregnancy (14.6%), meningitis (12.0%),
      HIV/AIDS (10.6%) and acute renal failure (8.0%). Seventy-nine percent of the
      maternal deaths occurred within 24 hours of admission. Most of the deaths were
      preventable. A regional-specific programme should be planned to reduce the
      deplorably high maternal mortality in north-central Nigeria.

PMID- 16623188
TI  - Why might clinicians in Malawi not offer HIV testing to their patients?
AB  - In order to identify reasons clinicians in Malawi might not offer HIV testing to
      patients, a cross-sectional descriptive postal census with telephone and fax
      follow-up was conducted. Proportions were calculated for each reason given for
      not offering HIV testing. Multiple logistic regression was used to determine
      whether responses differed by demographic characteristics. The response rate was
      54.3%. The five most common reasons for not offering HIV testing were: (1)
      inadequate training in HIV counselling (50.3%); (2) perception that the patient
      is not ready (49.5%); (3) no indication (35.6%); (4) testing facilities
      unavailable (35.4%); and (5) insufficient time (28.9%). Differences in reasons
      for not offering HIV tests amongst clinician groups were few. Thus, development
      of one general programme based on common reasons identified in this study could
      be effective in increasing HIV testing rates. Further investigation of the
      identified reasons should be undertaken to facilitate programme development.

PMID- 16623189
TI  - What is youth-friendly? Adolescents' preferences for reproductive health services
      in Kenya and Zimbabwe.
AB  - While there has been increased attention to youth-friendly reproductive health
      services, little research has been conducted among adolescents in developing
      countries to assess what characteristics of reproductive health services are most
      important to them. Large scale population-based surveys were carried out among
      youth in Kenya and Zimbabwe. A list of characteristics that programmers often
      think of as youth-friendly was read to respondents, after which they were asked
      to assess the importance of those characteristics in choosing their reproductive
      health services. Adolescents rated confidentiality, short waiting time, low cost
      and friendly staff as the most important characteristics. The least important
      characteristics included youth-only service, youth involvement and young staff,
      suggesting that adolescents do not prioritise stand-alone youth services such as
      youth centres, or necessarily need arrangements particular to youth such as youth
      involvement. The findings imply that most existing clinical services, even in the
      most resource-poor settings, are in a position to improve their level of youth
      friendliness.

PMID- 16623190
TI  - Men's role in emergency obstetric care in Osun State of Nigeria.
AB  - This study was conducted among the Yoruba of South-West Nigeria to examine the
      role of men in emergency obstetric care, as men determine whether and when their
      spouses visit health clinics in most cultures. Simple random sampling was used to
      select 900 households from three communities in Osun State, south-west Nigeria.
      Separate interviewers interviewed the man and his wife in each of the households.
      In polygamous families, two wives of reproductive age were also interviewed. The
      quantitative survey was complemented with a number of focus group discussions, in
      depth interviews and key informant interviews. There was high level of awareness
      of emergency obstetric conditions by men, particularly in relation to pregnancy
      signs and labour pains (53.2%). Respondents reported that men play useful roles
      during their partner's obstetric conditions (89.2%). Women take decisions on
      health-seeking behaviour during emergency obstetric conditions in the absence of
      the male partner. Education is found to be the major determinant of this change
      in male knowledge and behaviour. There is a need to further promote universal
      basic education in the country especially in areas where the observable change in
      this study has not been noted. There is also a need to extend the study to other
      zones in Nigeria in order to have a national picture.

PMID- 16623191
TI  - Socio-cultural barriers to voluntary blood donation for obstetric use in a rural
      Nigerian village.
AB  - Availability of blood for transfusion is of utmost importance in the fight
      against maternal morbidity and mortality. This study was conducted to identify
      the socio-demographic characteristics and reasons of persons declining voluntary
      blood donation. Patients' relatives declining blood donation in rural Ebonyi
      State were randomly recruited and interviewed using standardised questionnaire
      after obtaining informed consent from each of them. Responses were ranked
      according to frequency of positive respondents. Illiteracy was prevalent among
      the population: over 76% had no formal education. 'Not being strong enough' and
      'not having enough blood' were the two major reasons for declining blood
      donation, while loss of manhood/libido and exposure of blood to witchcraft were
      the other reasons given. Respondents' level of awareness of HIV/AIDS was
      appreciable. Socio-cultural barriers to voluntary blood donation exist in
      predominantly illiterate rural communities of the country. Most of the reasons
      given were based on misconception, misinformation and ignorance about the effect
      and safety of blood donation.

PMID- 16623192
TI  - Women's perception of partner violence in a rural Igbo community.
AB  - Partner violence is a serious public health problem affecting mostly women. This
      qualitative study assessed the perceptions of rural Igbo women of Nigeria of
      intimate partner violence. Information was elicited using in-depth interviews and
      focus group discussion. Women of childbearing age were selected from the various
      women age grades in Ozubulu, Anambra State, Nigeria. Findings revealed that the
      women generally condone and are complacent with intimate partner violence,
      perceiving it as cultural and religious norms. The women felt that reprimands,
      beating and forced sex affecting their physical, mental and reproductive
      wellbeing are normal in marriage. They did not support reporting such cases to
      the police or divorcing the man, they would rather prefer reporting to family
      members. They felt that exiting the marriage would not gain the support of family
      members. They also expressed fear for the uncertainty in re-marrying, means of
      livelihood after re-marriage, social stigmatisation, and concern for their
      children. Socio-cultural norms and structures favour partner violence in Anambra
      State of Nigeria. There is a need for advocacy and concerted action that will
      involve the educational, health, civil and religious sectors of the society to
      evolve sustainable structures that will empower women and provide support to
      enable victims to react appropriately to violence.

PMID- 16623193
TI  - Building alliances from ambivalence: evaluation of abortion values clarification
      workshops with stakeholders in South Africa.
AB  - A retrospective evaluation of attitudinal, behavioural and knowledge change among
      diverse stakeholder groups was conducted in Limpopo Province of South Africa to
      assess the effectiveness of a series of values clarification (VC) interventions.
      Telephone and face-to-face interview (193) results revealed that over two-thirds
      (70.2%) reported behavioural changes and 93.2% reported increased compassion for
      women who seek and providers who render termination of pregnancy. Behaviours
      supportive of the law were more likely among those initially undecided about
      their opinion of termination of pregnancy (p < 0.05) than among those initially
      opposed or supportive to it. When combined with supportive follow-up, three-day
      VC workshops may be effective at increasing CTOPA knowledge, changing attitudes
      and spurring advocacy behaviour to support reproductive choice. Research studies
      with pre-post and case-control designs are needed to confirm these preliminary
      results.

PMID- 16623194
TI  - Are process indicators adequate to assess essential obstetric care at district
      level?--a case study from Rufiji district, Tanzania.
AB  - To assess coverage and quality of essential obstetric care (EOC) and the
      appropriateness of using processindicators, a 3-month follow-up study was done in
      Rufiji district, Tanzania, involving 2 hospitals, 4 health centres, 10 large
      dispensaries and 10 randomly selected small dispensaries. Data collection was
      done on process indicators as suggested by UNICEF/WHO/UNFPA (UN) and 'unmet
      obstetric need (UON) for major obstetric intervention (MOI)'. With standard
      values in (brackets), the district had two comprehensive EOC facilities, births
      in EOC amounted to 62% (15%), met need for EOC was 76% (100%), caesarean section
      (C/S) rate 4.1% (> 5%), hospital case fatality rate (CFR) 1.0% (< 1%) and
      successful obstetric referrals 46% (100%). MOI for absolute maternal indication
      in the district was 2.6% (1-2%). All four maternal deaths occurred due to
      transport failures. The process indicators gave contradictory impressions on the
      coverage and quality of care and failed to link to the outcome of delivery
      complications in the study.

PMID- 16623195
TI  - An assessment of the clinical utility of routine antenatal screening of pregnant
      women at first clinic attendance for haemoglobin genotypes, haematocrit, ABO and
      Rh blood groups in Port Harcourt, Nigeria.
AB  - This prospective study was designed to provide the frequencies of the haemoglobin
      genotypes, ABO and Rh blood groups and their effects on the haematocrit values
      among pregnant women in Port Harcourt. One hundred and eighty (180) pregnant
      women at their first clinic attendance and in their first pregnancy (parity - 0)
      participated in this study. The overall frequencies obtained for ABO and Rh blood
      groups were: 26.67% for group A, 18.33% for B, 2.22% for AB and 52.78% for O. Rh
      D positive was 95.56% while Rh D negative was 4.44%. The frequencies of
      haemoglobin genotypes were 70.00% for HbAA, 29.44% for HbAS and 0.56% for HbSS.
      HbAC and SC did not occur in this study population. The mean haematocrit value
      was 34.64%. This was found to be independent of the ABO and Rh blood groups (P >
      0.05). On the other hand, haemoglobin genotypes were found to exert significant
      effects on the haematocrit values (F = 8.01, P = 0.0005). No significant
      relationship was found to exist between age and the haematocrit values. (F =
      0.91, P > 0.05). Since pregnancy in sickle cell disease is associated with
      morbidity, proper antenatal monitoring and counselling will be necessary to
      prevent fatal outcomes.

PMID- 16623196
TI  - Sexual harassment: the experience of out-of-school teenagers in Benin City,
      Nigeria.
AB  - Out-of-school teenage sexual harassment is a problem for both boys and girls in
      our society today, and the effects of this experience can affect their lives
      negatively in later adult life. The data on sexual harassment, particularly those
      on the out-of-school teenage population in Nigeria are very scanty, as a result
      of the sensitive nature of, and the stigma attached to the subject. This study
      sought to investigate the experiences of out-of-school teenagers with regards to
      sexual harassment in Benin City, Edo State, Nigeria. A survey method was used
      whereby a questionnaire was employed since most of the teenagers could not read.
      A total of 650 youths (293 males and 357 females) participated in the study. The
      findings indicate that sexual harassment is common out there in the streets, to
      the extent that it was viewed as the norm in the society by the youths. For
      example, 296 (83%) of all females and 152 (62%) of all males had experienced one
      or more forms of sexual harassment. It was also found that more females (82%)
      compared to 48% males experienced harassment and that anger was the most common
      response to the experience. The majority of the victims considered their
      assailants as abnormal and for the most part did not know how to handle the
      situation. The implications of these findings both for social/legal action and
      for health/sex education are discussed.

PMID- 16623197
TI  - Socioeconomic and reproductive factors associated with condom use within and
      outside of marriage among urban pregnant women in Zambia.
AB  - A cross-sectional questionnaire survey was conducted on 470 pregnant women in
      Lusaka, Zambia. Multivariate analysis revealed school attendance and child deaths
      as independently significant variables positively associated with HIV
      seropositivity. Among women with fidelity, HIV prevalence was not significantly
      lower, and condom use was much lower than among women who were having
      extramarital affairs. Factors significantly associated with condom use within and
      outside of marriage differed-age and number of live births within, and sexual
      transmission knowledge outside of marriage. School attendance was not effective
      for gaining knowledge on sexual transmission or condom use. Regular own earning
      was significantly effective for condom use in both groups, irrespective of school
      attendance. The following should be implemented intensively: effective education
      on HIV and sex in and out of school before early sexual debut, further
      implementation of family planning with emphasis on condom use, and empowering
      women by assisting with their economic independence.

PMID- 16623198
TI  - Swaziland's Traditional Birth Attendants Survey.
AB  - The Traditional Birth Attendants (TBAs) Survey in Swaziland was undertaken
      between March 27th 1996 and April 8th 1996. The objective of the survey was to
      generate reliable information regarding activities of TBAs in Swaziland. The
      survey was conducted in 25 Chiefdoms sampled out of a total of 206 Chiefdoms
      registered in Swaziland. The total number of sampled respondents in the 25
      Chiefdoms was 721. From the survey, it is estimated that there were probably 3000
      TBAs in the country, and in the majority of cases such TBAs would be a 51-year
      old woman who herself had delivered six children and had worked as a TBA for at
      least 10 years. Between 9,000 and 12,000 deliveries are estimated to take place
      out of health facilities. Of these many, nearly 43.5% are assisted by "TBAs";
      16.3% of woman interviewed deliver relative/family member and 15.1% are assisted
      by friends/neighbours, etc. Some of TBAs carry out procedures which are
      considered to be potentially harmful. Nearly 30% of TBAs have administered herbs;
      45% attend to abnormal deliveries (breech and multiple pregnancies); 26.7% re-use
      their cord cutting tools and in the case of haemorrhage 23.4% do manual
      procedures within reproductive tract of delivering women.

PMID- 16623199
TI  - Women's perceptions of pain and discomfort after childbirth in Angola.
AB  - Prophylactic treatment against postpartum haemorrhage is a widely investigated
      area and injection of Oxytocics has been considered as the best choice. The
      occurrence of postpartum pain and discomfort was studied in a population of
      birthing women in an overcrowded labour ward in Angola where the oxytocin-filled
      device Uniject was used. This study indicates that birthing women's perceived
      postpartum pain increases with parity and during breastfeeding, but does not
      confirm that injection of oxytocin increases pain and discomfort. This is an
      important finding, since it might facilitate the introduction of a management
      practice, likely to reduce haemorrhage-related maternal morbidity and mortality
      after delivery in underprivileged populations. The birthing women were, by and
      large, satisfied with the care and treatment provided, but the encounters with
      midwives seem to vary in quality. Further investigation is needed to elucidate
      parturient women's experience of postpartum pain and their perceptions of the
      quality of care and treatment.

PMID- 16623200
TI  - Utilisation of antenatal care in a Nigerian teaching hospital.
AB  - Records of 300 antenatal clinic attendees of a Nigerian teaching hospital were
      analysed. Results show that many of them obtained care only late in pregnancy and
      inadequately. Reasons for the delay in seeking antenatal care should be further
      investigated.

PMID- 16623201
TI  - Transmission of herpes simplex virus via oral sex.

PMID- 16623202
TI  - Screening and management of abdominal aortic aneurysm: the best evidence.

PMID- 16623203
TI  - Family physicians help meet the emergency care needs of rural America.
AB  - Ensuring access to emergency care in rural areas remains a challenge. High costs
      and low patient volumes make 100 percent staffing of rural emergency departments
      (EDs) by emergency medicine residency-trained physicians (EPs) unlikely. As
      rurality increases, so does the dependence on family physicians to provide
      quality emergent care.

PMID- 16623204
TI  - Glucosamine treatment for osteoarthritis.

PMID- 16623205
TI  - Benzodiazepines for alcohol withdrawal.

PMID- 16623206
TI  - Abdominal aortic aneurysm.
AB  - Most abdominal aortic aneurysms (AAAs) are asymptomatic, not detectable on
      physical examination, and silent until discovered during radiologic testing for
      other reasons. Tobacco use, hypertension, a family history of AAA, and male sex
      are clinical risk factors for the development of an aneurysm. Ultrasound, the
      preferred method of screening, is cost-effective in high-risk patients. Repair is
      indicated when the aneurysm becomes greater than 5.5 cm in diameter or grows more
      than 0.6 to 0.8 cm per year. Asymptomatic patients with an AAA should be
      medically optimized before repair, including institution of beta blockade.
      Symptomatic aneurysms present with back, abdominal, buttock, groin, testicular,
      or leg pain and require urgent surgical attention. Rupture of an AAA involves
      complete loss of aortic wall integrity and is a surgical emergency requiring
      immediate repair. The mortality rate approaches 90 percent if rupture occurs
      outside the hospital. Although open surgical repair has been performed safely, an
      endovascular approach is used in select patients if the aortic and iliac anatomy
      are amenable. Two large randomized controlled trials did not find any improvement
      in mortality rate or morbidity with this approach compared with conventional open
      surgical repair.

PMID- 16623207
TI  - Information from your family doctor. Abdominal aortic aneurysm (AAA): what you
      should know.

PMID- 16623208
TI  - Diagnostic approach to pleural effusion in adults.
AB  - The first step in the evaluation of patients with pleural effusion is to
      determine whether the effusion is a transudate or an exudate. An exudative
      effusion is diagnosed if the patient meets Light's criteria. The serum to pleural
      fluid protein or albumin gradients may help better categorize the occasional
      transudate misidentified as an exudate by these criteria. If the patient has a
      transudative effusion, therapy should be directed toward the underlying heart
      failure or cirrhosis. If the patient has an exudative effusion, attempts should
      be made to define the etiology. Pneumonia, cancer, tuberculosis, and pulmonary
      embolism account for most exudative effusions. Many pleural fluid tests are
      useful in the differential diagnosis of exudative effusions. Other tests helpful
      for diagnosis include helical computed tomography and thoracoscopy.

PMID- 16623209
TI  - Dementia with Lewy bodies: an emerging disease.
AB  - Dementia with Lewy bodies appears to be the second most common form of dementia,
      accounting for about one in five cases. The condition is characterized by
      dementia accompanied by delirium, visual hallucinations, and parkinsonism. Other
      common symptoms include syncope, falls, sleep disorders, and depression. The
      presence of both Lewy bodies and amyloidplaques with deficiencies in both
      acetylcholine and dopamine neurotransmitters suggests that dementia with Lewy
      bodies represents the middle of a disease spectrum ranging from Alzheimer's
      disease to Parkinson's disease. The diagnosis of dementia with Lewy bodies is
      based on clinical features and exclusion of other diagnoses. Individualized
      behavioral, environmental, and pharmacologic therapies are used to alleviate
      symptoms and support patients and their families. Cholinesterase inhibitors are
      more effective in patients who have dementia with Lewy bodies than in those with
      Alzheimer's disease. Conversely, patients who have dementia with Lewy bodies do
      not respond as well to antiparkinsonian medications. Anticholinergic medications
      should be avoided because they exacerbate the symptoms of dementia. Traditional
      antipsychotic medications can precipitate severe reactions and may double or
      triple the rate of mortality in patients who have dementia with Lewy bodies.

PMID- 16623210
TI  - Information from your family doctor. Dementia with Lewy bodies.

PMID- 16623211
TI  - Vulvodynia: diagnosis and management.
AB  - The diagnosis of vulvodynia is made after taking a careful history, ruling out
      infectious or dermatologic abnormalities, and eliciting pain in response to light
      pressure on the labia, introitus, or hymenal remnants. Several treatment options
      have been used, although the evidence for many of these treatments is incomplete.
      Treatments include oral medications that decrease nerve hypersensitivity (e.g.,
      tricyclic antidepressants, selective serotonin reuptake inhibitors,
      anticonvulsants), pelvic floor biofeedback, cognitive behavioral therapy, local
      treatments, and (rarely) surgery. Most women experience substantial improvement
      when one or more treatments are used.

PMID- 16623212
TI  - Information from your family doctor. Vulvodynia: what you should know.

PMID- 16623213
TI  - FPIN's clinical inquiries. Glucosamine and chondroitin for osteoarthritis.

PMID- 16623214
TI  - "Wood-grain" skin.

PMID- 16623215
TI  - Confronting a colleague who covers up a medical error.

PMID- 16623217
TI  - The application of wavelet and feature vectors to ECG signals.
AB  - The Electrocardiogram (ECG) is one of the most commonly known biological signals.
      Traditionally ECG recordings are analysed in the time-domain by skilled
      physicians. However, pathological conditions may not always be obvious in the
      original time-domain signal. Fourier analysis provides frequency information but
      has the disadvantage that time characteristics will be lost. Wavelet analysis,
      which provides both time and frequency information, can overcome this limitation.
      Here a new method, the combination of wavelet analysis and feature vectors, is
      applied with the intent to investigate its suitability as a diagnostic tool. ECG
      signals with normal and abnormal beats were examined. There were two stages in
      analysing ECG signals: feature extraction and feature classification. To extract
      features from ECG signals, wavelet decomposition was first applied and feature
      vectors of normalised energy and entropy were constructed. These feature vectors
      were used to classify signals. The results showed that normal beats and abnormal
      beats composed different clusters in most cases. In conclusion, the combination
      of wavelet transform and feature vectors has shown potential in detecting
      abnormalities in an ECG recording. It was also found that normalised energy and
      entropy are features, which are suitable for classification of ECG signals.

PMID- 16623216
TI  - Development of a 3-D convolution/superposition algorithm for precise dose
      calculation in the skull.
AB  - In this paper an algorithm for calculating 3-D dose distributions within the
      brain is introduced and adapted to the demands of modem radiosurgery. The dose
      calculation with this model is based on a 3-D distribution of the primary photon
      intensity which is calculated with a ray casting algorithm. A prelocated matrix
      takes into account field sizes as well as modifying elements as collimator
      positions (MLC), blocks, wedges and compensators. Monte Carlo precalculated
      monoenergetic kernels from 0.1 MeV to 50 MeV were at our disposal. The components
      of the spectrum were either determined by deconvoluting depth dose curves
      measured in water or analyzed with a Ge-Li detector system in the case of 60Co.
      The calculated fluence distribution has to be superposed to the complete kernel
      containing the spatial energy deposition. Inhomogeneities and tissue interface
      phenomena (rhoe, Z) have been investigated. The divergence of the rays and the
      curved surface of the patient are taken into account. Assuming homogenous media,
      it is possible to shorten the computation time by using the Fast Fourier
      Transformation (FFT) delivering a first overview within seconds. The algorithm
      was evaluated and verified under specific conditions of small fields as used in
      radiosurgery and compared to dose measurements and Monte Carlo calculations. In
      using both the fast algorithm (FFT) for mainly homogenous conditions on one hand
      and the very precise superposition for inhomogeneous cases on the other, this
      algorithm can be a very helpful instrument especially for critical locations in
      the skull.

PMID- 16623218
TI  - The prediction of transmitted dose distributions using a 3D treatment planning
      system.
AB  - Patient dose verification is becoming increasingly important with the advent of
      new complex radiotherapy techniques such as conformal radiotherapy (CRT) and
      intensity-modulated radiotherapy (IMRT). An electronic portal imaging device
      (EPID) has potential application for in vivo dosimetry. In the current work, an
      EPID has been modelled using a treatment planning system (TPS) to predict
      transmitted dose maps. A thin slab of RW3 material used to initially represent
      the EPID. A homogeneous RW3 phantom and the thin RW3 slab placed at a clinical
      distance away from the phantom were scanned using a CT simulator. The resulting
      CT images were transferred via DICOM to the TPS and the density of the CT data
      corresponding to the thin RW3 slab was changed to 1 g/cm3. Transmitted dose maps
      (TDMs) in the modelled EPID were calculated by the TPS using the collapsed-cone
      (C-C) convolution superposition (C/S) algorithm. A 6 MV beam was used in the
      simulation to deliver 300 MU to the homogenous phantom using an isocentric and
      SSD (source-to-surface) technique. The phantom thickness was varied and the
      calculated TDMs in the modelled EPID were compared with corresponding
      measurements obtained from a calibrated scanning liquid-filled ionisation chamber
      (SLIC) EPID. The two TDMs were compared using the gamma evaluation technique of
      Low et al. The predicted and measured TDMs agree to within 2 % (averaged over all
      phantom thicknesses) on the central beam axis. More than 90 % of points in the
      dose maps (excluding field edges) produce a gamma index less than or equal to 1,
      for dose difference (averaged over all phantom thicknesses), and distance-to
      agreement criteria of 4 %, 3.8 mm, respectively. In addition, the noise level on
      the central axis in the predicted dose maps is less than 0.1 %. We found that
      phantom thickness changes of approximately 1 mm, which correspond to dose changes
      on the central beam axis of less than 0.6 %, can be detected in the predicted
      transmitted dose distributions.

PMID- 16623220
TI  - Expected and observed changes to descriptors of trabecular architecture with
      aging--a comparison of measurement techniques.
AB  - The fragility of trabecular bone depends not only on the amount of bone but also
      on its architecture. In order to assess fragility of bone, describe changes due
      to age, and monitor effect of disease or treatment, it is necessary to model the
      physical properties of trabecular bone architecture. An important feature of bone
      architecture is the degree of anisotropy (DA). Estimates of DA may be obtained
      from computed tomography data by characterizing orientation in images. Widely
      used image descriptors for estimating orientation in this setting include mean
      intercept length (MIL), line fraction deviation (LFD), star length distribution
      (SLD) and star volume distribution (SVD). In this study, estimates of DA computed
      via each of these image descriptors are compared on synthetic images for various
      combinations of trabecular thickness, separation and number. Estimates of DA are
      also computed for real images representing different stages of aging. It is found
      that estimates of DA vary substantially depending on the choice of image
      descriptor. In particular, the MIL tends to underestimate DA.

PMID- 16623219
TI  - Acceptance testing and commissioning of Kodak Directview CR-850 digital
      radiography system.
AB  - This Technical Paper describes Acceptance Testing and Commissioning of the Kodak
      DirectView CR-850 digital radiography system installed at the Royal Adelaide
      Hospital. The first of its type installed in Australia, the system is a "dry"
      image processor, for which no chemicals are required to develop images. Rather,
      latent radiographic images are stored on photostimulable phosphor screens, which
      are scanned and displayed by a reader unit. The image can be digitally processed
      and enhanced before it is forwarded to a storage device, printer or workstation
      display, thereby alleviating the need to re-expose patients to achieve
      satisfactory quality images. The phosphor screens are automatically erased, ready
      for re-use. Results are reported of tests carried out using the optional "Total
      Quality Tool" quality assurance package installed with the system. This package
      includes analysis and reporting software which provides for simple testing and
      reporting of many important characteristics of the system, such as field
      uniformity, aspect ratio, line and pixel positions, image and system noise,
      exposure response, scan linearity, modulation transfer function (MTF) and image
      artefacts. Acceptance Tests were performed for kV and MV exposures. Resolution
      for MV exposures was at least 0.8 l/mm, and measured phantom dimensions were
      within 1.05% of expected magnification. Reproducibility between cassettes was
      within 1.6%. The mean pixel values on the central axis were close to linear for
      MV exposures from 3 to 10 MU and reached saturation level at around 20 MU for 6
      MV and around 30 MV for 23 MV beams. Noise levels were below 0.2 %.

PMID- 16623221
TI  - A new versatile hand dynamometer.
AB  - This paper describes the design and testing of a new hand strain-gauge based
      dynamometer. The design is portable and capable of measuring grip strengths from
      12.5 to 800N. The dynamometer is independent of point of application of the grip
      force. Finite element modelling and experimental testing were used to verify the
      mechanical system's suitability. The dynamometer was designed for input to a PDA
      to allow full portability of the device.

PMID- 16623222
TI  - A visual graphic/haptic rendering model for hysteroscopic procedures.
AB  - Hysteroscopy is an extensively popular option in evaluating and treating women
      with infertility. The procedure utilises an endoscope, inserted through the
      vagina and cervix to examine the intra-uterine cavity via a monitor. The
      difficulty of hysteroscopy from the surgeon's perspective is the visual spatial
      perception of interpreting 3D images on a 2D monitor, and the associated
      psychomotor skills in overcoming the fulcrum-effect. Despite the widespread use
      of this procedure, current qualified hysteroscopy surgeons have not been trained
      the fundamentals through an organised curriculum. The emergence of virtual
      reality as an educational tool for this procedure, and for other endoscopic
      procedures, has undoubtedly raised interests. The ultimate objective is for the
      inclusion of virtual reality training as a mandatory component for gynaecologic
      endoscopy training. Part of this process involves the design of a simulator,
      encompassing the technical difficulties and complications associated with the
      procedure. The proposed research examines fundamental hysteroscopy factors,
      current training and accreditation, and proposes a hysteroscopic simulator design
      that is suitable for educating and training.

PMID- 16623223
TI  - Motorcycling freedom: a paraplegics dream.
AB  - People with disabilities have the same rights as other members of society in
      directing and implementing the decisions which affect their lives, although it is
      not always afforded them due to physical limitations. A chance encounter by the
      author, a University of Western Australia mechanical engineering student, with a
      paraplegic man who expressed his dream of being able to ride a motorcycle again
      led to the design and build of a specially modified motorcycle that could be
      ridden safely and comfortably by a person without the use of their legs. The
      prototype involved several modifications which allow it to be ridden by a
      paraplegic person. They included, a thumb controlled pneumatic gear shifter, an
      integrated front and rear brake actuated with a single hand lever, ergonomic
      supports to hold the riders legs in place and an automatic stabilising system to
      balance the motorcycle at low speeds. The benefits that result from the inclusion
      of people with disabilities into regular leisure activities include normalisation
      as well as a sense of independence and freedom for the individual. It also
      allowed one man the chance to reach for his dreams.

PMID- 16623224
TI  - Time-frequency analysis of heart rate variability for neonatal seizure detection.
AB  - The ECG has been much neglected in automatic seizure detection in the newborn.
      Changes in heart rate and ECG rhythm are often found in animal and adult patients
      with seizure. However, little is known about heart rate variability (HRV) changes
      in human neonate during seizure. Results of ongoing time-frequency research are
      presented here with the aim to compare the performance of various time-frequency
      distributions (TFDs) when applied to HRV time series for non-seizure and seizure
      newborns. The TFDs studied are the Wigner-Ville (WVD), the Spectrogram (SP), the
      Choi-Williams (CWD) and the Modified B (MBD) distributions. Based on our
      preliminary results, our current conclusion is MBD outperforms other TFDs in
      terms of time-frequency resolution, cross-terms suppression and to represent the
      newborn HRV signals of non-seizure and seizure which are closely-spaced
      components in the time-frequency domain.

PMID- 16623225
TI  - Haptic rendering for VR laparoscopic surgery simulation.
AB  - This project concerns the application of haptic feedback to a VR laparoscopic
      surgery simulator. Haptic attributes such as mass, friction, elasticity,
      roughness and viscosity are individually modeled, validated and applied to the
      existing visual simulation created by researchers at Monash University. Haptic
      feedback is an essential element in an immersive and realistic virtual reality
      laparoscopic training simulator. The haptic system must display stable,
      continuous and realistic multi-dimensional force feedback, and its inclusion
      should enhance the simulators training capability. Stability is a recurring
      concern throughout haptic history, and will be tackled with the implementation of
      a stable control algorithm and a passive environment model. Haptic force feedback
      modeling, systems implementation and validation studies form the principal areas
      of new work associated with this project.

PMID- 16623226
TI  - Noninvasive detection of bilirubin using pulsatile absorption.
AB  - Bilirubin, the yellow substance usually responsible for neonatal jaundice, is
      currently monitored invasively or by observing/measuring skin colour. This paper
      investigates the feasibility of monitoring serum bilirubin concentration using
      light absorbance in a similar fashion to pulse oximetry. The light absorbance of
      bilirubin is shown to be sufficiently different to haemoglobin to in theory allow
      direct noninvasive serum bilirubin monitoring using light absorbance around
      480nm.

PMID- 16623227
TI  - EyeSim--an ophthalmic response simulator.
AB  - This paper pertains to the design, construction and development of an ophthalmic
      response simulator, intended to augment current neurological examination teaching
      practices in medical schools. Neurological examination of the eyes informs a
      practitioner of the functional state of certain cranial nerves (II, III, IV and
      VI) through the assessment of visual acuity, visual fields, ocular movements,
      external and internal eye structures and ophthalmoscopic examination. For the
      medical student, the interpretation of these indicators may be difficult,
      compounded by the infrequence with which such patients may be presented. As such,
      the need was identified for a simulator capable of replicating the ophthalmic
      response of patients with typical and a range of atypical neurologies. Such a
      simulator could be used as a stand-alone device or developed toward inclusion in
      pre-existing, life-size, hi-fidelity mannequins. Specifically, EyeSim will be
      able to track the movements of a pen-torch and vary the apparent dilation of an
      iris in response to changing levels of illumination. These responses can then be
      modulated to reflect certain deficits that neural pathologies may cause. At
      present the simulator comprises the electrical, electronic and mechanical
      components that replicate the pupillary response of the iris and the motility of
      the ocular muscles, a computer for the reception and analysis of a video signal
      and the micro-controller components, which determine the action of the physical
      components based on an array of inputs.

PMID- 16623228
TI  - Telecommunications access--matching available technologies to people with
      physical disabilities.
AB  - People with a disability do not have equitable access to the modern
      telecommunication medium. Many experience difficulty typing, handling the phone,
      dialling or answering calls. For those who are unable to speak, the only option
      is to type messages using whatever functional control site exists on their body.
      The provision of accessible mobile phones for people with disabilities can
      significantly improve their quality of life through an increased range of
      accessible activities, and can improve their independence, safety, security and
      self-esteem. This research was aimed at providing practical ways for people with
      a disability to participate in the extensive community of home and mobile phone
      users. The outcomes of ten participants taking part in the evaluation and trial
      of off-the-shelf telecommunication options are presented. Nine out of ten
      participants showed high to very high results in terms of their overall
      performance and satisfaction with the use of the telecommunication equipment
      provided. With the right policies, processes and support through equipment
      matching, education, training and delivery, current off-the-shelf solutions can
      help people with disabilities to effectively communicate with other members of
      our society and to access the same range of information systems and services
      enjoyed by able-bodied members of the community.

PMID- 16623229
TI  - Survey of Poincare indices for measuring heart rate variability.
AB  - Multiple indices have been developed to characterise the nonperiodic behaviour of
      heart rate variability displayed in Poincare plots, particularly with R-R
      interval data collected over 24hr periods. Some of these indices have been
      compared to statistical time-domain indices and some to spectral indices, while
      others have been used to separate data sets such as cardiac abnormalities. A
      survey of published indices for Poincare plot analysis was made covering
      literature through the 1990's to the present day. Statistical time-domain indices
      and the surveyed Poincare indices were used to analyse the same data set of R-R
      intervals that included: supine, standing, deep breathing, light exercise and
      recovery. This study examined these Poincare indices and determined their
      correlations with time-domain indices, and investigated how the correlations are
      affected by analysing shorter time periods. Further investigation of the Poincare
      indices that do not correlate strongly with SD or rMSSD may prove interesting in
      determining dynamic characteristics of cardiac nervous system activity.

PMID- 16623230
TI  - Neuro-muscular junction block stimulator simulator.
AB  - Improved technology and higher fidelity are making medical simulations
      increasingly popular. A simulated peripheral nerve stimulator and thumb actuator
      has been developed for use with the SimMan Universal Patient Simulator. This
      device incorporates a handheld control box, a McKibben pneumatic muscle and
      articulated thumb, and a remote software interface for the simulation
      facilitator. The system simulates the action of a peripheral nerve stimulator on
      the ulnar nerve, and the effects of neuromuscular junction blocking agents on the
      thumb motion.

PMID- 16623231
TI  - Absolute linearity measurements on a PbS detector in the infrared.
AB  - The nonlinearity characteristics of a commercially available thin-film
      photoconductive PbS detector were experimentally investigated in the infrared
      using the National Physical Laboratory detector linearity characterization
      facility. The deviation from linearity of this detector was shown to be
      significant even for relatively low values of radiant power incident on the
      active area of the detector. For example, the linearity factor was approximately
      0.8 when 0.6 microW of radiant power at a wavelength of 2.2 microm was
      illuminating a spot of 1 mm in diameter on the active area of the PbS detector.
      These figures demonstrate the poor linearity characteristics of this detector and
      provide a warning to other users of PbS detection systems. The deviation from
      linearity was shown to be a function of the size of the spot being illuminated on
      the detector active area, as well as the wavelength of the incident radiation.
      The deviation from linearity was shown to be a function of irradiance
      illuminating the detector for irradiance values lower than 1 microW mm(-2).

PMID- 16623232
TI  - Investigation of polarization-induced fading in fiber-optic interferometers with
      polarizer-based polarization diversity receivers.
AB  - A technique is described to eliminate polarization-induced fading in fiber-optic
      interferometers with two or three polarizers. Modeling and simulation show that
      two polarizers should be angularly spaced by 90 degrees to alleviate polarization
      induced fading. A test system is set up with two 6.5 km fiber coils to link the
      data. A bistate polarization diversity receiver is tested for reducing
      polarization-induced fading. The signal is demodulated using a digital phase
      generated carrier and the system demonstrates self-noise up to 7.7
      microrad/square root Hz (at 1 kHz).

PMID- 16623233
TI  - Time-averaged in-line digital holographic interferometry for vibration analysis.
AB  - Time-averaged in-line digital holography is applied for vibration analysis. In
      particular, by use of a double-exposure approach, simultaneous determination of
      vibration mode shape and mean static state deformation during a vibration cycle
      are obtained. The subtraction of two numerically reconstructed digital holograms
      recorded at the same resonant frequency but with a small difference in amplitude
      shows the mixing of Bessel-type time-averaged fringes owing to vibration and of
      the double-exposure fringes owing to differences in the mean deformation of the
      object. It is shown that separation of these fringe patterns can be readily
      accomplished numerically. An experimental demonstration of this effect by use of
      in-line digital holography for relatively small membranes is demonstrated.

PMID- 16623234
TI  - GaN-based stacked micro-optics system.
AB  - A prototype of a GaN-based stacked micro-optics system is demonstrated. The
      system consists of a GaN microlens, GaN membrane gratings, six spacers, a spatial
      filter, and a 980 nm VCSEL. The laser beam is collimated by the GaN microlens and
      diffracted by the GaN membrane grating. The systems can be used in blue-violet-UV
      micro-optics systems.

PMID- 16623235
TI  - Precision analyses of a stitching interferometer testing system.
AB  - The most basic task in subaperture stitching test work is to confirm the
      precision of the system. We propose a method with which to calculate the system's
      precision. Statistical theory, especially regressive analysis, is employed. To
      discuss the statistical characteristics of all the random variables is the
      objective of the precision analyses. The results show that the number of sample
      points and the connatural error of the interferometer are the most important
      factors in the analyses.

PMID- 16623236
TI  - Spin-on-glass coatings for the generation of superpolished substrates for use in
      the extreme-ultraviolet region.
AB  - Substrates intended for use as extreme-ultraviolet (EUV) optics have extremely
      stringent requirements in terms of finish. These requirements can dramatically
      increase the cost and fabrication time, especially when nonconventional shapes,
      such as toroids, are required. Here we present a spin-on-glass resist process
      capable of generating superpolished parts from inexpensive substrates. The method
      has been used to render diamond-turned substrates compatible for use as EUV
      optics. Toroidal diamond-turned optics with starting rms roughness in the 3.3-3.7
      nm range have been smoothed to the 0.4-0.6 nm range. EUV reflectometry
      characterization of these optics has demonstrated reflectivities of approximately
      65%.

PMID- 16623237
TI  - Path of a beam of light through an optical coating.
AB  - A simple model for the path of a light beam through an optical coating is the
      path of a ray predicted by Snell's law. By determining the exit point of a beam
      for various types of coating, one finds that the simple model is a good
      approximation in the case of antireflection coatings, but not for coatings of
      other designs. An approximate method for determining the correct path of a beam
      through the coating is derived and the path is illustrated using a Gaussian
      incident beam and tracing the position of the peak field of the beam as it
      traverses the coating.

PMID- 16623238
TI  - Correction of photoresponse nonuniformity for matrix detectors based on prior
      compensation for their nonlinear behavior.
AB  - What we believe to be a novel procedure to correct the nonuniformity that is
      inherent in all matrix detectors has been developed and experimentally validated.
      This correction method, unlike other nonuniformity-correction algorithms,
      consists of two steps that separate two of the usual problems that affect
      characterization of matrix detectors, i.e., nonlinearity and the relative
      variation of the pixels' responsivity across the array. The correction of the
      nonlinear behavior remains valid for any illumination wavelength employed, as
      long as the nonlinearity is not due to power dependence of the internal quantum
      efficiency. This method of correction of nonuniformity permits the immediate
      calculation of the correction factor for any given power level and for any
      illuminant that has a known spectral content once the nonuniform behavior has
      been characterized for a sufficient number of wavelengths. This procedure has a
      significant advantage compared with other traditional calibration-based methods,
      which require that a full characterization be carried out for each spectral
      distribution pattern of the incident optical radiation. The experimental
      application of this novel method has achieved a 20-fold increase in the
      uniformity of a CCD array for response levels close to saturation.

PMID- 16623239
TI  - Optoelectronic approach to adaptive radio-frequency transversal filter
      implementation with negative coefficients by using optical spectrum shaping.
AB  - A multitap negative and positive coefficient radio-frequency transversal filter
      is implemented by using a digital-micromirror-device spatial light modulator for
      weighting-factor control and a chirped fiber Bragg grating for time-delay
      control. The demonstrated architecture is reconfigurable, has high speed and low
      loss, and is robust through digital programmability for a wide variety of
      filtering algorithms. A design using an interleaver for differential detection
      realizes an ultrahigh bandwidth with a maximum processable frequency of 33.7 GHz.
      A multitap low-pass filter, a negative tap notch filter with 40 dB attenuation,
      and a multitap negative coefficient bandpass filter are experimentally
      demonstrated. The results are in agreement with theory.

PMID- 16623240
TI  - Compression of interference patterns with application to phase-shifting digital
      holography.
AB  - A compression method of phase-shifting digital holographic data is presented.
      Three interference patterns are recorded, and holographic information is
      extracted from them by phase-shifting interferometry. The scheme uses standard
      baseline Joint Photographic Experts Group (JPEG) or standard JPEG-2000 image
      compression techniques on the recorded interference patterns to reduce the amount
      of data to be stored. High compression rates are achieved for good reconstructed
      object image quality. The utility of the proposed method is experimentally
      verified with real holographic data. Results for compression rates using JPEG
      2000 and JPEG of approximately 27 and 20, respectively, for a normalized root
      mean-square error of approximately 0.7 are demonstrated.

PMID- 16623241
TI  - Initialization of iterative parametric algorithms for blind deconvolution of
      motion-blurred images.
AB  - Performances of iterative blind deconvolution methods for motion-blurred images
      are usually reduced depending on the accuracy of the required initial guess of
      the blur. We examine this dependency, and a two-stage restoration procedure is
      proposed: First we perform a direct technique with a single straight-forward
      process to produce a rough initial estimate of the blur, and then an iterative
      technique is employed to refine the blur estimate. Two common iterative
      techniques (the expectation-maximization and the Richardson-Lucy methods) are
      examined here and implemented in the combined direct-iterative modification for a
      variety of motion blur types. Results show that the combined method significantly
      improves the reliability of the deconvolution process.

PMID- 16623242
TI  - Influence of composition on the photorefractive centers in pure LiNbO3 at low
      light intensity.
AB  - The influence of composition on the photorefractive effect in pure LiNbO3
      crystals at low light intensity was investigated. The experimental results
      indicate that different defects dominate the photorefractive centers of pure
      LiNbO3 with various compositions. Bipolarons are considered to be responsible for
      the enhanced photovoltaic field in reduced near-stoichiometric LiNbO3, and their
      bulk photovoltaic constant kappa is estimated to be approximately 6.95 x 10(-32)
      m3/V. Q polarons (composed of two bipolarons) are introduced to explain the
      photorefractive effect of congruent LiNbO3 at both low and high light
      intensities.

PMID- 16623243
TI  - Image oversampling for page-oriented optical data storage.
AB  - Page-oriented data storage systems incorporate optical detector arrays [such as
      complementary metal-oxide semiconductor (CMOS) arrays] in order to read data
      images. For laboratory demonstrations the detector array is typically pixel
      matched to the data image [Opt. Lett. 22, 1509 (1997)]. This approach requires
      exceedingly high-performance optics and mechanics for the simultaneous alignment
      of each data-bearing pixel image to a detector element to be achieved. Systems
      intended for commercialization are designed with detector arrays that spatially
      sample the image at or above the Nyquist rate in order to read poorly aligned and
      distorted images [S. Redfield, Holographic Data Storage (Springer-Verlag, 2000),
      pp. 347-349]. However, for data page sizes exceeding a megapixel this approach
      becomes prohibitive in terms of detector bandwidth, size, power, cost, and
      processing requirements. We have instead developed a sub-Nyquist oversampling
      methodology that can recover arbitrarily aligned and distorted megapixel data
      page images with pixel-matched fidelity by using fewer than double the number of
      detector pixels. Features required for practicable implementation are described,
      including fiducials for alignment determination.

PMID- 16623244
TI  - Tungsten source integrated cavity output spectroscopy for the determination of
      ambient atmospheric extinction coefficient.
AB  - Broadband integrated cavity output spectroscopy (ICOS) utilizing an incoherent
      tungsten lamp as a spectroscopic source is described. This novel approach has
      been termed W-ICOS. The technique has been applied to make quantitative
      measurements of Rayleigh scattering by carbon dioxide between 570 and 590 nm and
      to make measurements of aerosol and atmospheric extinction. Minimum detectable
      extinction coefficients (kext) made in a 94 cm optical cavity ranged between 3.4
      and 35 Mm(-1) depending on the level of signal averaging employed. The level of
      sensitivity achieved should allow measurements on static gas samples and regular,
      quantitative measurements of the atmospheric extinction coefficient.

PMID- 16623245
TI  - Spaceborne profiling of atmospheric temperature and particle extinction with pure
      rotational Raman lidar and of relative humidity in combination with differential
      absorption lidar: performance simulations.
AB  - The performance of a spaceborne temperature lidar based on the pure rotational
      Raman (RR) technique in the UV has been simulated. Results show that such a
      system deployed onboard a low-Earth-orbit satellite would provide global-scale
      clear-sky temperature measurements in the troposphere and lower stratosphere with
      precisions that satisfy World Meteorological Organization (WMO) threshold
      observational requirements for numerical weather prediction and climate research
      applications. Furthermore, nighttime temperature measurements would still be
      within the WMO threshold observational requirements in the presence of several
      cloud structures. The performance of aerosol extinction measurements from space,
      which can be carried out simultaneously with temperature measurements by RR
      lidar, is also assessed. Furthermore, we discuss simulations of relative humidity
      measurements from space obtained from RR temperature measurements and water-vapor
      data measured with the differential absorption lidar (DIAL) technique.

PMID- 16623246
TI  - Low-threshold self-starting femtosecond Ti:sapphire laser.
AB  - A low-threshold self-starting Kerr-lens mode-locked Ti:sapphire laser is
      demonstrated that uses a tight-focusing cavity design in conjunction with a
      semiconductor saturable-absorber mirror (SESAM). With 3% and 12% output couplers,
      we achieve mode-locking thresholds as low as 390 and 600 mW, respectively. Stable
      femtosecond laser pulses with average power of 114 mW are generated at a pump
      power of 1.2 W, which corresponds to a typical duration of 17 fs and bandwidth of
      47 nm. Mode-locking operation is achieved in a pump power range of 600 mW to 4.8
      W at an output coupling of 12%; the advantages of using a SESAM for low-power
      mode-locking operation are demonstrated.

PMID- 16623247
TI  - High-power and high-quality, green-beam generation by employing a thermally near
      unstable resonator design.
AB  - We have obtained green-beam quality of M2 = 6.2 at an average output power of 120
      W by intracavity frequency doubling of a diode-side-pumped, Q-switched Nd:YAG rod
      laser with a repetition rate of 10 kHz and an optical-to-optical conversion
      efficiency of 15.2%. To achieve high-beam quality at high average power, the
      laser employs a thermally near-unstable resonator design with two-rod
      birefringence compensation in an L-shaped flat-flat cavity. The output power
      fluctuation of the green laser remains less than 0.9% in 4 h.

PMID- 16623248
TI  - Maximum-likelihood estimation of a laser system pointing parameters by use of
      return photon counts.
AB  - A maximum-likelihood estimator used to determine boresight and jitter performance
      of a laser pointing system has been derived. The estimator is based on a Gaussian
      jitter model and uses a Gaussian far-field irradiance profile. The estimates are
      obtained using a set of return shots from the intended target. An experimental
      setup with a He-Ne laser and steering mirrors is used to study the performance of
      the proposed method. Both Monte Carlo simulations and experimental results
      demonstrate excellent performance of the estimator. Our study shows that
      boresight estimation is more challenging than jitter estimation when both
      quantities are estimated. Furthermore, their estimation performance improves with
      an increase in the number of shots. The experimental results are found to agree
      well with the simulation results.

PMID- 16623249
TI  - Effects of unwanted feedback on synchronized chaotic optical communications.
AB  - The effects of unwanted external optical feedback on synchronized chaotic optical
      communication systems are studied numerically. We consider an open-loop
      configuration consisting of a transmitter laser with double external optical
      feedbacks and a receiver laser with optical injection from the transmitter laser.
      First, including the effects of unwanted optical feedback, the synchronization
      performances of both the complete synchronization and the generalized
      synchronization are examined. Then the encoding and decoding performances of the
      generalized synchronization and the effects of the introduced feedback are
      investigated, respectively. Finally, we study the control of the unwanted
      feedback on the dynamics of the transmitter laser and briefly discuss the system
      security when the transmitter laser is driven to operate in a steady state or
      periodic oscillation state by the additional feedback.

PMID- 16623250
TI  - Effects of excited-state absorption on two-photon absorbing materials.
AB  - Many chromophores with a large two-photon absorptive cross section are hybrid
      materials where the two-photon absorption (TPA) is coupled to an excited-state
      absorption (ESA). We develop a numerical technique to investigate hybrid two
      photon processes in nonlinear absorbers. Our numerical method compares well with
      published results. In addition to customary calculation of the transmission
      curve, we demonstrate the importance of the ESA following the TPA, which may
      cause significant temporal and radial distortion. We also show that improvements
      in the transmission can result in significant radial and temporal pulse
      distortion, which may actually reduce the material effect.

PMID- 16623251
TI  - Multipass acoustically open photoacoustic detector for trace gas measurements.
AB  - What we believe to be a novel multipass, acoustically open photoacoustic detector
      designed for fast-response, high-sensitivity detection of trace gases and
      pollutants in the atmosphere is demonstrated. The acoustic pulses generated by
      the absorption of the light pulses of a tunable optical parametric oscillator by
      target molecules are detected by an ultrasonic sensor at 40 kHz. The
      photoacoustic signal is enhanced by an optical multipass arrangement and by
      concentration of the acoustic energy to the surface of the ultrasonic sensor. The
      detection sensitivity, estimated from CO2 measurements around a 2 microm
      wavelength, is approximately 3.3 x 10(-9) W cm(-1).

PMID- 16623252
TI  - Ultrafast pump-probe surface plasmon resonance spectroscopy of thin gold films.
AB  - A time-resolved reflection pump-probe method was combined with a surface plasmon
      resonance technique in Kretschmann geometry for the investigation of ultrafast
      light-induced processes in thin films. Transient changes in the gold layer's
      reflectivity were observed when the layer was excited by 3 ps duration pulses
      with photon energy exceeding the interband transition and by probing with photon
      energy close to the interband transition. Comparison of the experimental and
      modeling results has shown that the imaginary part of the dielectric function of
      gold increases linearly during excitation, whereas the real part remains
      unchanged. The decay of the light-induced changes has two components. The first
      component is faster than the pulse duration, and the second is much longer than
      1.5 ns; they are related to cooling of the electron plasma and lattice,
      respectively.

PMID- 16623253
TI  - Simple system for optical short-pulse generation in both active mode-locking and
      self-seeding schemes.
AB  - A simple system that simultaneously supports active mode-locking and self-seeding
      schemes for wavelength-tunable optical short-pulse generation is proposed. The
      system consists of a gain-switched Fabry-Perot laser diode, an erbium-doped fiber
      amplifier, a tunable optical filter, and two circulators. The mode-locked optical
      pulses exhibit good stability, a high side-mode suppression ratio of more than 31
      dB over a wide wavelength tuning range of 42 nm, and a pulse width of around 35
      ps at a repetition frequency of approximately 2.8 GHz.

PMID- 16623254
TI  - Design, assembly, and optical bench testing of a high-numerical-aperture
      miniature injection-molded objective for fiber-optic confocal reflectance
      microscopy.
AB  - The design, analysis, assembly methods, and optical-bench test results for a
      miniature injection-molded plastic objective lens used in a fiber-optic confocal
      reflectance microscope are presented. The five-lens plastic objective was tested
      as a stand-alone optical system before its integration into a confocal microscope
      for in vivo imaging of cells and tissue. Changing the spacing and rotation of the
      individual optical elements can compensate for fabrication inaccuracies and
      improve performance. The system performance of the miniature objective lens is
      measured by use of an industry-accepted slanted-edge modulation transfer function
      (MTF) metric. An estimated Strehl ratio of 0.61 and a MTF value of 0.66 at the
      fiber-optic bundle Nyquist frequency have been obtained. The optical bench
      testing system is configured to permit interactive optical alignment during
      testing to optimize performance. These results are part of an effort to
      demonstrate the manufacturability of low-cost, high-performance biomedical optics
      for high-resolution in vivo imaging. Disposable endoscopic microscope objectives
      could help in vivo confocal microscopy technology mature to permit wide-scale
      clinical screening and detection of early cancers and precancerous lesions.

PMID- 16623255
TI  - [Multimodal evoked potential abnormalities in patients with Wilson's disease].
AB  - The aim of this study was to investigate the involvement of the following
      functional systems: somatosensory evoked potentials (SSEP), visual evoked
      potentials (VEP), and event related potentials (ERP), in twenty patients with
      Wilson's disease (WD). VEP and SSEP abnormalities were discovered in 8 patients
      respectively (40%), whereas ERP were either absent or, in the case of 10 patients
      (50%), had significantly prolonged P-300 latencies. Taken together, at least one
      evoked potential abnormality was discovered in 17 patients (85%). Only in 3
      patients (15%), involving either the isolated hepatic type of disease or short
      illness duration of the neurological type, were normal evoked potential findings
      observed. Our findings suggest the usefulness of multimodal evoked potential
      abnormalities in the evaluation of subclinical manifestations in patients with
      WD.

PMID- 16623256
TI  - [Implantable "loop recorder"--a new diagnostic tool for syncope of unknown
      cause].
AB  - INTRODUCTION: The implantable loop recorder (ILR) is a new diagnostic tool in
      cardiology for establishing the causes of unexplained syncope in patients where
      standard conventional tests, invasive tests included, have failed. The device is
      a diagnostic "pacemaker," surgically implanted underneath the skin of the chest,
      with leads attached to the case of the device, not requiring endovenous lead
      implantation. Heart rhythm is monitored continuously on the basis of an endless
      loop, up to a maximum period of 14 months. Recording is carried out either by
      applying an outside activator whenever symptoms occur, or automatically,
      according to a pre-set algorithm for bradycardia, tachycardia, and/or asystolic
      detection. OBJECTIVE: The aim of this study was to present this new diagnostic
      method as well as our first experiences with its implementation. METHOD: We
      followed 5 patients (3 male, 2 female, mean age: 46.4 +/- 19) who had ILRs
      ("Reveal Plus," Medtronic Inc., USA) implanted at our centre, over a period of 14
      months (7.6 +/- 5.5), concentrating on their clinical course, symptom occurrence,
      and electronically monitored heart rhythm at the time of ILR auto activation
      and/or recordings triggered by outside activation whenever a patient's symptoms
      were discernible. RESULTS: In three patients, the ILR revealed syncope aetiology
      by documenting heart rhythm at the time of its occurrence. In one patient,
      involving a lethal outcome, the ILR was not explanted, so that the rhythm at the
      time of the fatal syncope, although assumed, remained undocumented. In one, most
      recently implanted patient, follow-up is still in progress. CONCLUSION: The
      implantable loop recorder represents an important innovation and a step forward
      in establishing the causes of recurrent syncope, which cannot be determined by
      standard invasive and non-invasive testing.

PMID- 16623257
TI  - [Brain abscesses in neonates: neurosonographic diagnosis and long-term follow
      up].
AB  - Brain abscesses were neurosongraphically diagnosed in 3 out of 44 neonates who
      had confirmed purulent meningitis. In two cases, the cause was Proteus
      mirabillis, whereas in one the cause could not be isolated. The ultrasound
      finding indicated abscess cavities localised in the frontal (in one case
      bilaterally) and temporal regions of the CNS. Neurosurgical interventions were
      carried out on all of the neonates who had abscesses (including the evacuation of
      purulent cavity contents, and later on a ventriculoperitoneal shunt in two cases,
      because of the development of hydrocephalus). Follow-up on the operated infants
      revealed that one infant died at the age of 9 months; one, who had a bilateral
      abscess, demonstrated significant neurodevelopmental retardation in the third
      month of his life (so far it has not been brought under control); while the third
      one, whom we monitored until the age of 2, displayed regular psychomotor
      development (preserved intellect, motor skills, sight, and hearing).

PMID- 16623258
TI  - [Clinical manifestations of cow milk protein intolerance in infants].
AB  - INTRODUCTION: The disorder of cow milk protein intolerance is characterised by a
      wide spectrum of clinical manifestations caused by hypersensitivity of type I,
      II, or IV, and occurs in 2-3% of children, mostly infants. OBJECTIVE: The aim of
      this study was to present our experiences and observations of clinical signs and
      symptoms of cow milk protein intolerance in infants aged below 12 months. METHOD:
      The investigation was carried out on a sample of 55 infants, aged between 1.5-9
      months (X = 4.21 +/- 1.25), who had cow milk protein intolerance. Diagnosis of
      illness was based on characteristic anamnestic, clinical, and laboratory
      parameters, as well as on an adequate patient's response to antigen elimination.
      RESULTS: The clinical presentation of cow milk protein intolerance was dominated
      by cutaneous problems, found in 40/55 (72.73%) infants, followed by digestive
      disorders, found in 31 (56.36%), while respiratory tract disorders were observed
      least frequently (14.55%). None of the patients developed anaphylactic shock.
      Changes involving only one system were found in 35 (63.64%) patients; of these 20
      (36.36%) were cutaneous and 15 (27.27%) digestive. Twenty (36.36%) infants
      displayed multisystemic changes; of these 12 were cutaneus with digestive, 4 were
      cutaneus with respiratory, while 4 infants had cutaneous, digestive, and
      respiratory disorders. Of the 55 infants with cow milk protein intolerance, 26
      (47.27%) had urticaria, 22 (40.00%) perioral erythema, 21 (38.18%) diarrhoea (15
      haemorrhagic, 6 non-haemorrhagic), 13 (23.64%) vomiting, 12 (21.82%) Quincke's
      oedema, 12 (21.82%) eczema, 5 (9.09%) obstructive bronchitis, while 3 (5.45%)
      infants had laryngitis. In 5 (9.09%) patients we found a significant body weight
      deficit and in 3 (5.45%), sideropenic anaemia, while longitudinal growth
      retardation was not registered in any of the patients. CONCLUSION: Our study
      showed that the disorder of cow milk protein intolerance predominantly involved
      cutaneous disorders as well as combinations of cutaneous and digestive disorders,
      while respiratory system disorders proved to be relatively rare.

PMID- 16623259
TI  - [Frequency and characteristics of hepatitis B infection in children with
      malignant diseases].
AB  - INTRODUCTION: Hepatitis B, a complication of blood transfusion or other means of
      transmission, occurs with variable frequency in children with malignant diseases.
      OBJECTIVE: The objective of this study was to determine the frequency of
      hepatitis B virus infection in children with malignant diseases, to investigate
      the clinical course of the illness, and to analyse the influence of hepatitis on
      cytotoxic treatment. METHOD: The study included children diagnosed and treated
      for malignant diseases at the University Children's Hospital in Belgrade from
      1997 to 2003. HBs Ag was analysed in all patients who had elevated transaminases
      of twice normal value, in children who had icterus, and in one group of patients
      treated routinely after 2001 before, during, and after therapy. RESULTS A total
      of 137 male and 107 female children who had malignancies were treated. From 113
      children who were evaluated for the presence of HBs Ag at the beginning of
      treatment, 2 (1.7%) were HBsAg+. In this group of patients HBsAg was tested in 58
      (51%) children during and after chemotherapy, and HBsAg was discovered in 17
      (29%) of them. Of 123 children, in whom HBsAg was not tested at the beginning of
      their illness, 36 (55%) out of 66 (51%) tested patients were HBsAg+. No
      statistical difference between those two groups of patients was ascertained (chi2
      = 3.27, p > 0.05). In summary, the presence of HBsAg was discovered in 53
      patients, 22% out of 244 patients and 43% of tested patients. Nine patients had
      the icteric form of illness, with one case proving fatal due to fulminating
      hepatitis. CONCLUSION: Taking into consideration the uncertain long-term
      prognoses of these patients, follow-up and treatment is essential.

PMID- 16623260
TI  - [Subclinical peripheral neuropathy in type 1 diabetic adolescents and its
      relationship with metabolic control].
AB  - Professional management of paediatric diabetology, according to consensus
      guidelines, involves the screening of microvascular complications at puberty. The
      subclinical form of peripheral neural dysfunction in diabetic teenagers is
      reported with a frequency of 50-88%, by different authors. The purpose of this
      study was to evaluate the frequency of subclinical distal neuropathy (DSMN) in
      type 1 diabetic paediatric patients during the second decade of life, and its
      relationship with metabolic control. The Endocrinology Department and the
      Neurology-Physiology Laboratory of the Paediatric Clinic in Belgrade carried out
      a longitudinal follow-up study (lasting 18 months, beginning in November 2000) on
      a selection of patients with poor metabolic control. During routine clinical
      treatment, patients were evaluated using the electrophysiological diagnostic
      method on peripheral neural dysfunction, a subclinical form of neuropathy.
      Metabolic control was manifested through HbA1c levels, measured every 3 months,
      using ion-exchange chromatography. Finally, here is the data collected from the
      clinical follow-up investigation of 60 children, aged 13-19 (median 15.5 +/-
      2.2), with duration of diabetes from 2-16 years (median 6.3 +/- 3.6), and on the
      following therapies: 43 CT-conventional and 17 IIT-intensive, and insulin dose/
      day, median 1.02 (0.6-2.1) U/kg. Detected DSMN parameters at the beginning and at
      the end of the study were also noted. DSMN frequency was positive, at 64% for
      HbA1c of 9.44; DSMN dysfunction was reversed in 5% of the patients, for HbA1c of
      10.17; the worst result was the progression of DSMN at 6.7% for HbA1c of 10.52;
      6.7% had negative DSMN, with improved metabolic control, for HbA1c of 8.4; 15% of
      the examinations were unfinished (+/*). ANOVA statistical analysis showed a
      significant statistical relationship between metabolic control (HbA1c levels) and
      DSMN neuropathy (sig. 0.043, p < 0.05). There was no significant relationship
      between the reversion of DSMN and improved HbA1c, although a numeric distinction
      did exist. On the clinical aspect, there was a significant relationship between
      insulin dosage and age (p < 0.01, sig. 0.007). This data demonstrates the
      influence of metabolic regulation on neuropathy. Better metabolic control can
      slow the progression of subclinical peripheral neural dysfunction (DSMN) in
      diabetic children.

PMID- 16623261
TI  - [Focal nodular hyperplasia].
AB  - Thanks to ultrasonography, computed tomography, and nuclear magnetic resonance,
      not only symptomatic but also asymptomatic liver tumours are discovered more
      frequently than before. Focal nodular hyperplasia (FNH) is one such tumour, most
      frequently an asymptomatic tumour of the liver, which predominantly appears in
      women during the generative period, who have taken oral contraceptives for
      several years. We present a 27-year-old woman, who has never taken either oral
      contraceptives or other hormones, in whom a left lobe liver tumour was
      unexpectedly discovered during a routine investigation performed for psychiatric
      complaints. The tumour, removed by left lateral bisegmentectomy (segments II and
      Ill), was composed of two tumoural nodes: 70x58x47 mm and 20x20x20 mm, the bigger
      one of which had a light grey central stellate scar. Histology revealed a focal
      nodular hyperplasia. The postoperative recovery was uneventful and the patient
      stayed symptom free for more than three years after surgery.

PMID- 16623262
TI  - [Pseudoallescheria boydii (Scedosporium apiospermum), cause of mycotic
      granulomatous osteomyelitis--case diagnosis].
AB  - Fungal bone infections constitute about 0.1-0.2% of all osteomyelitis cases. The
      disease, mycetoma pedis, most often affects the feet and is also known as madura
      foot. Mycetoma, extremely rare in this geographic area, is endemic in tropical
      and subtropical regions. We present a case of mycetoma pedis (madura foot). The
      patient was a 50-year-old woman. The clinical signs included pain, indurations,
      and local redness. The anamnesis was very long, about 10 years. The operative
      material was routinely stained with haematoxylin-eosine [HE]. Granulomatous
      inflammation of the bone was confirmed pathologically. All pathological
      characteristics pointed to a fungal infection in the form of mycetoma pedis.
      Special staining for fungi was performed: PAS, Grocott's hexamine-silver, and
      Giemsa, confirming the diagnosis of mycetoma. A definitive microbiological
      analysis was carried out through tissue inoculation on the Sabouraud dextrose
      agar laboratory media for fungal cultivation. Pseudoallescheria boydii, the
      sexual stage of Monosporium apiospermum, was isolated. After microbiological
      verification of fungal infection, surgical therapy was carried out. Seven months
      after the first operation, the patient had the same clinical signs. The
      diagnostic procedure was repeated and mycetoma was confirmed once again. Surgery
      was again the therapy of choice, because Pseudoallescheria boydii is resistant to
      treatment with antimycotic drugs.

PMID- 16623263
TI  - [Drainage as a rare cause of intestinal incarceration].
AB  - Silicone drains are often placed in the abdominal cavity for prophylactic
      reasons. One complication resulting from drainage includes visceral herniation at
      the drain site of the abdominal wall defect. An 82-year-old woman underwent a
      laparotomy for a large pelvic mass. After the operation, she developed small
      bowel incarceration, which was caused by aggressive drain extraction. Subsequent
      surgical treatment resulted in the patient's full recovery. This case emphasises
      the unusual causative mechanism of intestinal obstruction. Drains should be
      placed carefully in the abdominal cavity in strictly selected cases, only when it
      is reasonable to do so.

PMID- 16623264
TI  - [Use of saliva as a diagnostic fluid in dentistry].
AB  - Saliva is a secretion of the salivary and mucous glands and is of major
      importance in the maintainance of oral health. Over the last few decades, saliva
      has been evaluated as a diagnostic fluid in medicine for determining systemic
      disease markers as well as for monitoring numerous drugs, narcotics, and
      hormones. The biochemical analysis of saliva is particularly important in
      dentistry. The estimation of the risk of appearance and diagnosis of disease,
      monitoring of disease progression, evaluation of therapy efficacy for caries,
      periodontitis, premalignant and malignant oral lesions, as well as infectious
      diseases of the oral cavity, can be assessed by analysing different constituents
      of saliva. Individuals at risk of caries can be identified using tests that
      determine saliva flow rate, saliva buffer capacity, and colonisation of the oral
      cavity by cariogenic bacteria. Today, these rapid and simple diagnostic tests are
      used routinely in caries risk determination. The study and use of saliva-based
      diagnostics have increased over the last few decades. Clinical testing of saliva
      shows much promise. However, there is a need for much additional research in this
      area, before the true clinical value of saliva as a diagnostic fluid in dentistry
      can be determined.

PMID- 16623265
TI  - [New strategies in multiple organ dysfunction syndrome therapy for sepsis].
AB  - Despite more than 20 years of extensive research, sepsis and/or trauma induced
      multiple organ dysfunction syndrome (MODS) remain the chief cause of death in
      intensive care units, with mortality rates between 30% and 80%. Early goal
      directed therapy (EGDT), use of drotrecogin alfa (activated), tight control of
      hyperglycaemia, and adrenal replacement therapy (low doses of corticosteroids),
      all constitute new treatment strategies. In future, a combination of therapies
      should be individually adjusted for each patient.

PMID- 16623266
TI  - [Oncogenic viruses and their role in tumour formation].
AB  - Oncogenic viruses trigger persistent infections, which can stimulate uncontrolled
      cell growth by inducing cell transformation. Different oncogenic viruses use
      different mechanisms for infecting cells. Most oncogenic DNA viruses integrate
      transforming sets of genes into the host chromosome and encode proteins that bind
      and inactivate cell growth regulatory proteins, such as p53 and retinoblastoma
      gene product. Tumourous RNA viruses use different oncogenic mechanisms. Some of
      them encode oncogenic proteins that are almost identical to the cellular proteins
      involved in the control of cellular growth. The overproduction or altered
      function of these oncogenic materials stimulates cell growth. These RNA viruses
      can cause tumours rapidly. The second group of oncoviruses integrates their
      promoter sequences and viral enhancers near to the cellular growth-stimulating
      gene, initiating the transformation of the cell. The third group of RNA tumour
      viruses encodes a protein tax that transactivates the expression of cellular
      genes. Virus-induced malignant transformation of the cell represents the first
      step in the complex process of oncogenesis.

PMID- 16623267
TI  - [Boleslas Matuszewki--pioneer of medical film-making].
AB  - Boleslas Matuszewski, born in 1856, was a pioneer in medical film-making. He
      worked simultaneously on improving his movie camera, film-making, collecting film
      documentation, and the idea of establishing an archive of medical films. Although
      his first attempts at filming and showing surgical operations didn't gain
      widespread approval, he was not discouraged, and succeeded in garnering support
      from a number of French doctors, who realised the importance of his ideas, not
      only in filming and forming medical film documentation, but also in the use of
      film for educative purposes. His visionary ideas gained acceptance when Dr.
      Doyen, on the occasion of the 66th Convention of the British Medical Society, in
      1898, used film material as part of his lecture. Shortly afterwards, the Medical
      Academy took steps to show certain operative techniques, which represented both
      the confirmation and fruition of Matuszewski's ideas about filmmaking and the
      establishment of an archive of medical films.

PMID- 16623268
TI  - [Catheter ablation--the first choice method in the therapy of artial flutter].

PMID- 16623269
TI  - [The meaning of the transesophageal echocardiography in the detection of the
      cardiogenic and aortal embolization in the focal cerebral ischemia and the
      transitory ischemic attacks].

PMID- 16623270
TI  - [The clinical symptoms, the diagnostics and the therapy of orthostatic
      intolerance].

PMID- 16623271
TI  - [The complications during the therapy for multiple myeloma].

PMID- 16623272
TI  - [Mutational analysis of LQT genes in individuals with drug induced QT interval
      prolongation].
AB  - BACKGROUND: In a long list of non-cardiovascular drugs a risk of QT interval
      prolongation and thus an increased risk of malignant arrhythmias has been
      described. The precise mechanism remains unclear. Many of these drugs are potent
      blockers of cardiac ion channels. Thus, prolongation of repolarization could be
      caused by latent ion channel genes mutations which are revealed under stress
      conditions. GROUP OF PATIENTS AND METHODS: Patients were recruited in screening
      of antipsychotic drugs with proarrhythmic potential, another sporadic cases were
      reffered from regional hospitals. In 13 individuals pathologic values of
      corrected QT interval (> 0.44 s in males, > 0.46 s in females) were observed.
      Eleven patients gave their consent to mutational analysis of KCNQ1, KCNH2, SCN5A,
      KCNE1, KCNE2 and KCNJ2 genes (associated with congenital long QT syndrome).
      RESULTS: At present complete results of mutational analysis are available in 8
      patients. In 5 individuals changes in DNA sequence were found which are
      considered normal variants according to the literature (nucleotide and aminoacid
      polymorphisms, intronic variants). In 1 male a KCNQ1 gene mutation A590T was
      identified (yet not reported in literature). CONCLUSION: Mechanisms of drug
      induced QT interval prolongation is complex and it cannot be explained simply by
      ion channel disorders.

PMID- 16623273
TI  - [The meaning of the combination of fibrinogen, micro/macroalbuminuria and
      atheromatosis in the carotid bloodstream for the evaluation of the abnormal
      finding of the stress myocardial SPECT in the asymptomatic 2nd type diabetic
      patients].
AB  - OBJECTIVES: Stress perfusion myocardial scintigraphy (SPECT) is useful in silent
      ischemia detection in the group of the asymptomatic type 2. diabetic patients. In
      our paper we present the combinations of the parameters predictive for stress
      myocardial SPECT result. METHODS: We selected parameters (fibrinogen,
      micro/macroalbuminuria, ateroma in carotid artery bed) that were significantly
      associated with stress myocardial SPECT result. We analyzed the combinations of
      these parameters change and evaluated their significance for stress myocardial
      SPECT result prediction. RESULTS: We evaluated 121 type 2. diabetic patients
      without patological ECG changes and with normal left ventricle ejection fraction.
      Thirty one (26%) had abnormal and 90 (74%) equivocal or normal stress myocardial
      SPECT result. The combination of ateroma presence in carotid bed and fibrinogen
      in upper tertile was found in 20 patients. Fifteen of them (75%) had the abnormal
      SPECT result. The combinations of the ateroma absence, negative
      micro/macroalbuminuria and fibrinogen in the middle or lower tertile were present
      almost in the half of all the examined diabetic patients. Such combinations were
      connected with normal or equivocal SPECT result in 93-96% cases. CONCLUSION:
      Micro/macroalbuminuria, fibrinogen and ateroma in carotid bed found by sonography
      are significantly associated with stress myocardial SPECT result. Combinations of
      these parameters changes lead to the futher stratification that enables the
      rationale approach in the stress examination indication.

PMID- 16623274
TI  - [Idiopathic premature ventricular complexes--catheter ablation as a therapeutic
      alternative].
AB  - Frequent isolated ventricular premature complexes (VPCs) in patients without
      major structural heart disease are generally associated with benign prognosis,
      however can lead to serious symptoms and also to the development of left
      ventricular dysfunction. Purpose of this study is to present mapping findings and
      immediate results of catheter ablation of frequent idiopathic VPCs, and
      evaluation of long-term clinical outcome and the role of catheter ablation in
      clinical practice. METHODS: Twenty-seven patients, aged 48 +/- 14 years without
      major structural heart disease, presenting with frequent VPCs, were investigated
      electrophysiologically in 28 procedures. Twenty-five patients underwent catheter
      ablation. RESULTS: In 19 patients, the ectopic focus was found in the right
      ventricular outflow tract (RVOT) and could be reached from the endocardial
      approach. In these patients, VPCs were successfully eliminated by the ablation.
      Comparison of 24-hour Holter ECG recordings showed complete elimination of the
      target VPCs in all the cases [18,483 +/- 12,790 (2,152-48,820)/17 +/- 10 (3-42) %
      VPCs before ablation vs. 94 +/- 219 (0-763)/0.01 +/- 0.2 (0-0.7) % VPCs after
      ablation]. In 5 patients, mapping revealed epicardial localization of the ectopic
      focus in the OT. Ablation endocardially from the RVOT failed in 2 of the
      patients, cryoablation epicardially from the venous system was partially
      successful in 1 patient, and no ablation was attempted in 2 patients. In another
      3 patients, ectopic foci were found in other parts of the ventricles and ablation
      was completely successful in one case. During the 14 +/- 9 (1-34) month follow-up
      period, full elimination of the target VPCs and elimination or significant
      reduction of symptoms was achieved in 20 (74%) patients. The procedures were
      accomplished without complications and with fluoroscopy time of 8,2 +/- 5,9
      minutes. CONCLUSION: Catheter ablation of frequent idiopathic VPCs was performed
      effectively and safely, particularly, if the ectopic focus was localized on the
      endocardial aspect of the RVOT. Efficacy of catheter ablation ofVPCs arising from
      the epicardium of ventricular OT or other atypical sites is limited by
      inaccessibility or proximity to the conduction system. Indication to more
      aggressive mapping and ablation methods like intrapericardial approach or
      ablation from inside the venous system should be always critically considered
      with regard to the symptoms or other clinical risk factors.

PMID- 16623275
TI  - [Can we cure atrial flutter with radiofrequency ablation in an hour?].
AB  - BACKGROUND: Radiofrequency ablation of common atrial flutter requires the
      creation of a complete transmural ablation line across cavotricuspid region to
      achieve bidirectional conduction block. Irrigated tip catheters facilitate rapid
      achievement of this block by creation larger and deeper lesions. The EASTHER
      registry was organized to collect data about the efficacy of the procedure in
      small and middle volume centres in Central and Eastern Europe, all using
      THERMOCOOL catheter technology. METHODS: Easther is a prospective registry (April
      2002-February 2003). 133 consecutive patients (81.1% male, age 59.0 +/- 10.4
      years, range 30-81 years) with common atrial flutter were enrolled. Coincidence
      with atypical flutter was observed in 2.7%. Patients had a history of flutter of
      31.0 +/- 53.6 month (range 1-403) and concomitant atrial fibrillation was
      observed in 42.9%. Structural heart disease was present in 38.9%. Amount of re
      ablated cases was 14%. RF energy was applied during 60 sec in power-controlled
      mode at a setting between 40 to 50 W with an average flow rate of 19.0 ml/min.
      RESULTS: Acute success rate defined as bi-directional block was achieved in
      93.1%, although 94.7% of cases were assessed successful by the treating
      electrophysiologist. Average number of RF applications was 12.0 +/- 7.0 (range 2
      40) per procedure. Average delivered power varied between a minimum of 36.1 +/-
      15.1 W till a maximum of 45.3 +/- 13.0 W, while the average maximum temperature
      observed at the same time was varied between 39.0 +/- 3.4 degrees C and 45.4 +/-
      4.0 degrees C. Total procedure time was 100.1 +/- 42.7 min (range 20-280 min) and
      fluoroscopy time was 15.8 +/- 9.6 min (range 4-45 min). In comparable French TC
      registry Average total and fluoroscopy time were 46.4 +/- 33.6 min, and 10.0 +/-
      6.8 min resp. In the Middle European centres total and fluoroscopy time was 96.1
      +/- 40.9 min, and 15.0 +/- 8.9 min resp. In centres from Eastern Europe it was
      120.3 +/- 51.2 min, and 20.4 +/- 11.9 min resp. Two adverse events were reported.
      Both patients had strong chest pain during ablation. These results are comparable
      with the literature data published. CONCLUSIONS: Irrigated tip catheters are
      effective and safe in ablation of common atrial flutter. This technology helps to
      accelerate and facilitate achievement of bi-directional isthmus block. Most of
      procedures were terminated to one hour in experienced centers in France as early
      as 2002. Procedures not exceeding one hour are feasible in case of spreading this
      method as method of first choice with gaining of experiences in centres of Middle
      and Eastern Europe.

PMID- 16623276
TI  - [Autoimmune thyropathies in diabetics].
AB  - Autoimmune thyropathies are frequent in patients with type 1 diabetes mellitus.
      Some recently published papers confirm similarly high prevalence of autoimmune
      thyropathies also in patients with type 2 diabetes mellitus. Chronic autoimmune
      thyroiditis is the most frequent form of autoimmune thyropathies. Authors
      examined 79 accidentally selected diabetics (38 women and 41 men, x = 55.4 +/-
      2.8). Diabetic patients were divided into three groups. 20 patients with type 1
      diabetes mellitus - classical form were the first group, 12 patients with LADA
      were the second group and 47 patients with type 2 diabetes mellitus constituted
      the third group. Authors diagnosed chronic autoimmune thyroiditis in 8 (40 %)
      patients in the group of patients with type 1 diabetes mellitus, in 6 (50%) in
      the group of patients with LADA and in 20 (43%) of patients with type 2 diabetes
      mellitus. They didn't find out statistically more frequent prevalence of chronic
      autoimmune thyroiditis in all groups of patients with diabetes (patients with
      type 1 diabetes mellitus, patients with LADA, patients with type 2 diabetes
      mellitus) in comparison with control group of non-diabetic subjects. They found
      out statistically significant more frequent prevalence of chronic autoimmune
      thyroiditis in diabetics of woman gender and in diabetics with positive family
      history of thyropathies. Results of paper confirm recommendation of examining
      once or twice a year autoantibodies against thyroid gland and level of
      thyrotropin (TSH) with the aim of early finding of laboratory manifestation of
      thyroidal autoimmunity or developing functional disorder.

PMID- 16623277
TI  - [The role of transesophageal echocardiopgraphy in detection of cardiogenic and
      aortic sources of embolism in stroke and transient ischaemic attacks].
AB  - OBJECTIVES: To prospectively investigate the prevalence of definite and potential
      sources of cardiogenic embolism and embolism from ascending aorta and aortic arch
      in patients with a cryptogenic stroke or transient ischaemic attack (TIA).
      MATERIAL/METHODS: The study group consisted of 218 consecutive patients (146
      males, mean age 59.4 +/- 11.5, range 38-83 years) without significant stenoses of
      carotic and vertebral arteries. All patients underwent biplane/multiplane
      transesophageal echocardiography (TEE). 77.5% of patients suffered a stroke and
      22.5% had a TIA. Sinus rhythm was in 74.8% of the patients, atrial fibrillation
      in 22.0% and pacemaker rhythm in 3.2%. RESULTS: 1. Definite source of embolism
      was identified in 21.6% of patients. The most frequent finding was a thrombus of
      the left atrial (LA) appendage - 12.4%. Less frequently found were mobile
      thrombus of aortic arch - 3.7%, thrombus of LA body - 2.3%, left ventricular
      thrombus - 2.3%, thrombus of valvular prosthesis - 1.4% and heart tumor - 0.5%.
      2. The total prevalence of potential sources of embolism was 61.5%. Only
      potential source (without definite source) was demonstrated in 52.3% of patients.
      Very frequently were found patent foramen ovale - 58.3% and atherosclerosis of
      ascending aorta or aortic arch - 53.7%. Further sources were LA spontaneous
      echocontrast - 21.1%, reduced function of LA appendage - 18.3%, atrial septal
      aneurysm - 7.8%, atrial septal defect - 1.4%, cardiac foreign body - 0.5%. 3. TEE
      did not reveal any source of embolism in 26.1% of patients. CONCLUSIONS: 1. 21.6%
      of the patients suffering from stroke/TIA without hemodynamically significant
      stenoses of extracranial cerebral arteries had a definite cardiogenic or aortic
      source of embolism, 2. additional 52.3% of patients had only potential source of
      embolism (without definite source), 3. we consider TEE necessary in patients with
      stroke/TIA without a known etiology, despite complete neurological examination
      and transthoracic echocardography.

PMID- 16623278
TI  - [The meaning of viral kinetics in the beginning of the pegylated interferon-alpha
      and ribavirin therapy for chronic hepatitis C].
AB  - Pegylated interferon alpha (PEG-IFN) and ribavirin combination therapy is the
      contemporary standard therapy of the patients chronically infected with hepatitis
      C virus (HCV). OBJECTIVE OF THE STUDY: The study is monitoring the changes in
      viremy through the changes of HCV RNA in serum before and during antiviral
      therapy and it attempts to find a relationship between the viral kinetics in the
      beginning of the therapy and the sustained virologic response. SET OF THE
      PATIENTS AND THE METHODICS: The study involved 133 patients with chronic
      infection with HCV, of the average age of 38 years (ranged 18-68 years). 86 of
      them were men. There were 88 patients who had not been treated before (naive
      patients), 19 of them were relabing and 26 were non-responders to the previous
      therapy with conventional IFNalpha and ribavirin. 106 patients (80%) were
      infected with genotype (G) 1, 3 (2%) with G2, 18 (14%) with G3, 1 patient with G4
      and 1 with G6 (under 1%), in 4 (3%) the genotype could not be determined. All of
      them were treated with the combination of PEG-IFNalpha-2a (180 microg once a
      week) and ribavirin (800 mg per day in the infection with G2 or G3, 1000 mg at
      the infection with G1 and the weight up to 74 kg, 1200 mg per day at the
      infection with G1 and the weight 75 kg and higher). RESULTS: Up to now, 122
      patients completed the therapy and 93 of them (76%) had negative HCV RNA in serum
      at the time of completion of the therapy. Negative HCV RNA after 24 weeks
      (sustained virologic response SVR) after the completion of the therapy had 64/107
      (60%) of the treated patients. In the course of 12 weeks of the therapy the
      viremy decreased by at least 2 decadic logarithms (early virologic response -
      EVR) in 87 patients (82%) and in 63 of them (72%) also SVR was noted. Only 19
      patients had not EVR and just 1 one of them, nevertheless, achieved SVR (5%).
      CONCLUSION: The achievement of EVR is a prerequisite to the successful therapy
      for chronic infection with HCV with the combination of PEG-IFNalpha and
      ribavirin. Quantitative determination of HCV RNA in serum before and during
      antiviral therapy is a prerequisite to the modern antiviral therapy for chronic
      infection with HCV.

PMID- 16623279
TI  - [Medical device Task Force Monitor in diagnostics of syncope by means of head-up
      tilt table testing].
AB  - Head-up tilt table testing is used for diagnostics of vasovagal syncope. Beat-to
      beat blood pressure recording and ECG monitoring is not sufficient for
      clarification of the syncope mechanisms in individual patients, however. That is
      why a Task Force Monitor was developed in Graz, Austria. In addition this device
      enables stroke volume recording by impedance method. Other advantages are
      calculations of cardiac output, beat-to-beat total peripheral resistance, heart
      rate variability and baroreflex sensitivity as well as activity ofsympathicus and
      parasympathicus assessment. These methods enable detailed hemodynamic analysis
      during the whole head-up tilt testing duration, the moment of syncope including.

PMID- 16623281
TI  - [The standard diagnostic and therapeutic method in genetic (hereditary)
      hemochromatosis. The recommended method of the Czech Hepatologic Society of the
      Czech Medical Society of J. E. Purkyne].

PMID- 16623280
TI  - [The role of STAT proteins in the regulation of the response to the interferone
      alpha therapy in chronic hepatitis C].
AB  - The currently used standard treatment for chronic hepatitis C using a dual
      combination of IFNalpha/RBV is only successful in 50% cases. With the exception
      of some clinical and biochemical factors, degree of inflammation (grading) and
      degree of fibrosis (staging), there are no other known markers which may serve as
      valid predictors of response to therapy. Interference of hepatitis C virus (HCV)
      with signaling pathways modulated by JAK-STAT, ERK 1/2, NFkappaB and MAP proteins
      is one mechanism which may influence the interaction between HCV and IFNalpha.
      These proteins regulate different cell processes such as activation of cytokines,
      activation of apoptosis, regulation of cell proliferation etc. Therefore, it is
      possible that impaired signaling or inhibition/dysregulation of some of these
      proteins by HCV infection may cause resistance to IFNalpha treatment. This review
      is completed by results of preliminary study the aim of which was
      immunohistochemical assessment and analysis of expression of STAT 2, 3 proteins,
      their inhibitors SOCS 2, 3 and PIAS 3 and proteins JAK 1 and ERK 1/2 in liver
      biopsies of 26 patients with chronic hepatitis C treated by dual combination
      IFNalpha/RBV and subsequent correlation of the results of immunohistochemical
      analysis (histoscore) with histological picture and clinical response to
      treatment. The results shows increased expression of STAT 3, STAT 2 and ERK 1
      proteins and decreased expression of SOCS 3 and SOCS 2 in hepatocytes of patients
      with more marked inflammation and fibrosis. In patients with sustained
      virological response there was increased expression of SOCS 3 and JAK 1 and
      decreased expression of SOCS 2. Relapse was associated with increased expression
      of SOCS 3 and PIAS 3. However, owing to the small sample size, the results only
      approximated statistical significance, but we suggest that proteins of STAT
      family and their inhibitors SOCS and PIAS probably play an important regulatory
      role during response to treatment for chronic hepatitis C.

PMID- 16623282
TI  - [Osteonecrosis of the jaw in the course of multiple myeloma treatment and
      bisphosphonate administration].
AB  - The osteonecrosis of jaws is a phenomena newly described in the connection with
      bisphosphonate therapy. We describe a case of a 41 years old man with multiple
      myeloma, who developed the osteonecrosis of jaw in the course of antimyeloma
      therapy. The men had tooth pain from the beginning of the chemotherapy, but the
      extraction was performed till one month before high dose chemotherapy with
      peripheral stem cell transplantations, when the conservative therapy was find
      unsatisfactory. Bisphosphonate were administered from the beginning of the
      chemotherapy, the bisphosphonate therapy was started with clodronate and later
      changed to zoledronate. One year from the tooth extraction the wound did not
      heeled and therefore resection of the necrotic bone was performed. The pain in
      the jaw was diminished, but the wound is not completely heeled. The
      administration of bisphosphonate was stopped after the diagnosis osteonecrosis of
      the jaws.

PMID- 16623283
TI  - [Tachycardia-induced cardiomypathy: less usual causes, less usual treatment: 3
      case-reports].
AB  - Tachycardia-induced cardiomypathy is a potentially reversible form of left
      ventricular dysfunction and heart failure that is often neglected in clinical
      practice. Three case-reports of tachycardia-induced cardiomyopathy associated
      with three different tachyarrhythmias, cured by catheter ablation, are presented.
      All cases were characterized by specific clinical conditions. Potential
      consequences of inadequate clinical analysis and treatment are discussed.

PMID- 16623284
TI  - Look beyond disappointment.

PMID- 16623285
TI  - The case for regional pay.

PMID- 16623286
TI  - Bureaucratic barrier.
AB  - Nurses wanting to change jobs can face long delays waiting for Criminal Records
      Bureau (CRB) checks to come through. Some have even ended in debt as a result.
      CRB checks can be delayed if the forms are not completed correctly. According to
      the CRB, 98 per cent of standard disclosures are completed within two weeks.
      Enhanced disclosures--for staff working in the sole supervision of children or
      vulnerable adults--are completed within four weeks in 90 per cent of cases.

PMID- 16623287
TI  - Critical alert.
AB  - Picking up patient problems early has reduced the number of unplanned admissions
      to critical care. At The London Clinic this is achieved through a scoring system
      and a critical care outreach team. The outreach team is nurse-led. A scoring
      system alerts ward nurses to call the team. Under patient group directives,
      oxygen and intravenous fluid treatment can be modified. A patient group directive
      for the use of colloid is being developed.

PMID- 16623288
TI  - Caring in a forgotten land.
AB  - Since Saparmurat Niyazov became president of Turkmenistan, its healthcare system
      has spiralled downwards, with the closure of hospitals and the sacking of
      thousands of nurses. Turkmenistan became independent from the Soviet Union in
      1991. Patients have to pay for their health care, but few can afford it. There is
      no distinct nursing role and no nursing leadership structure.

PMID- 16623289
TI  - More harm than good.

PMID- 16623290
TI  - A painful price to pay for childbirth.

PMID- 16623291
TI  - The land of the lost souls.

PMID- 16623292
TI  - Nursing students' understanding of the Glasgow Coma Scale.
AB  - AIM: To explore third year nursing students' understanding of the Glasgow Coma
      Scale (GCS). METHOD: An explorative survey using a semi-structured questionnaire
      was used. A convenience sample of 65 third year nursing students was selected
      from a university faculty of nursing in Scotland. Of 65 questionnaires
      distributed, 39 were returned, giving a 60 per cent response rate. FINDINGS: Most
      respondents (n= 24, 62 per cent) were not confident in practical use of the GCS.
      However, they wanted to improve their theoretical knowledge as well as their
      practical skills. CONCLUSION: A short training course is needed to make sure that
      students are able to use the GCS effectively while minimising errors.

PMID- 16623293
TI  - Computer-based education for patients with psychosis.
AB  - AIM: To evaluate the use of a computer-delivered psycho-education programme which
      tries to improve patients' knowledge and understanding of psychosis. METHOD: The
      study used a qualitative approach to gather opinions from participants (n=10)
      using semi-structured interviews. FINDINGS: The results indicated that patients
      in forensic psychiatry were able to use the CD-ROM with relative ease. They found
      it acceptable and enjoyable to use and had little difficulty working through the
      programme and developing their own relapse prevention plan. CONCLUSION: The study
      suggests that patients with psychosis are willing to try new ways to learn about
      their illness and enjoy learning about a complex and sensitive subject. CD-ROM is
      a useful way to deliver information on psychosis, which may appeal to the younger
      patient population, who are more familiar with computer technology.

PMID- 16623294
TI  - Improving communication for people with learning disabilities.
AB  - Patients with learning disabilities have higher healthcare risks than the general
      population. Health professionals need to develop skills that enable them to
      communicate effectively with this patient group. Identifying barriers to
      communication is the first step to reducing or removing them. Suggested
      strategies to improve healthcare access for patients with learning disabilities
      include: developing individualised health action plans, simplifying communication
      styles and providing accessible facilities and tailored resources.

PMID- 16623295
TI  - Type 2 diabetes in adults.

PMID- 16623296
TI  - The future in our hands.

PMID- 16623297
TI  - Take a break and...breathe.

PMID- 16623298
TI  - How to kick your career into action.

PMID- 16623299
TI  - No time to lose.

PMID- 16623300
TI  - Multidetector-row helical CT enteroclysis.
AB  - The authors illustrate the technique for small-bowel imaging using enteroclysis
      with multidetector-row computed tomography (MDCT), underscoring the important
      role played by CT in the assessment of the small bowel thanks to the advent of
      first the spiral and later the multidetector technique. The paper makes a
      detailed comparison of the various methods that have been used in CT study of the
      small bowel and proposes a standardised technique to achieve correct distension
      of bowel loops and adequate evaluation of bowel wall vascularity, making
      reference to the well-consolidated experiences of the various Italian research
      groups. The paper accurately describes the different procedures required for CT
      assessment of the small bowel, from nasojejunal intubation to the selection of
      the most appropriate acquisition phases for assessment of bowel wall vascularity.

PMID- 16623301
TI  - Retrospective study of 23 cases of hepatic infarction: CT findings and
      pathological correlations.
AB  - PURPOSE: The aim of this study was to retrospectively review the cases of hepatic
      infarction diagnosed at our institute using conventional, spiral and multislice
      computed tomography (CT) over the last decade in order to describe its
      morphological and density characteristics and define its possible
      etiopathogenesis. MATERIALS AND METHODS: Twenty-three consecutive patients aged
      27-65 years with hepatic infarction were studied by CT at our institute over a
      period of about 10 years. A conventional CT unit was used in seven patients, a
      helical CT scanner in ten and a multislice CT in six. CT was performed before and
      after the administration of 130-150 cc of contrast material infused at a rate of
      3-3.5 ml/s. RESULTS: CT showed hepatic infarction due to arterial causes in 19
      cases, 11 of which were in liver transplant patients. The infarction was related
      to right hepatic artery embolisation to control haemorrhage (one case),
      chemoembolisation of a multifocal hepatocarcinoma in a cirrhotic liver (one
      case), arterial mesenteric infarction due to thromboembolism (two cases),
      necrotising pancreatitis (one case), surgery in pancreatic cancer invading the
      hepatic artery (one case), pancreaticoduodenectomy (two cases), portal thrombosis
      in a young woman with pregnancy-related clotting disorder (one case), haemolytic
      anaemia, elevated liver enzymes, low platelet count (HELLP) syndrome (one case);
      eclampsia and disseminated intravascular coagulation (DIC) (one case) and acute
      exacerbation of Budd-Chiari syndrome (one case). At CT scans, hepatic infarction
      was depicted as a hypodense parenchymal area, at times triangular in shape, with
      sharp peripheral contours (12 cases) or as a rounded central or marginal area
      (four cases) with irregular appearance (three cases), with lobar extension (two
      cases) and ill-defined shape (two cases). Moreover, CT showed intralesional gas
      not correlated to bacterial infection (two cases). In all surgical cases, the
      results were confirmed by pathology. CONCLUSIONS: CT is the method of choice in
      the diagnosis of hepatic infarction, providing useful information regarding site,
      morphology, and extent of the lesion. Furthermore, in most cases, CT is able to
      suggest the possible aetiology and guide appropriate management.

PMID- 16623302
TI  - Magnetic resonance imaging of the prostate with spectroscopic imaging using a
      surface coil. Initial clinical experience.
AB  - PURPOSE: The purpose of this study was to evaluate the diagnostic ability of
      proton magnetic resonance spectroscopic imaging (MRSI) in the detection and
      localisation of prostate cancer, prospectively compared with histopathologic
      findings. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) and MRSI were
      performed on 39 patients with prostate-specific antigen (PSA) levels greater than
      4 ng/ml and suspicious findings at trans-rectal ultrasound (TRUS). All patients
      underwent a TRUS ten-core biopsy within 30 days according to a subdivision of the
      prostate into octants. All studies were interpreted by a dedicated radiologist
      who reported the areas of interest as normal, equivocal or suspicious on MRI. At
      MRSI, cancer was defined as possible if the ratio of choline plus creatine to
      citrate exceeded mean normal peripheral zone values by two standard deviations
      (SD) or as definite if that ratio exceeded the normal value by three SD. MRI and
      MRSI findings were spatially correlated with findings obtained from individual
      biopsy sites. RESULTS: MRI and MRSI alone had sensitivity, specificity, positive
      and negative predictive values and diagnostic accuracy in the detection of
      prostate cancer equal to 85%, 75%; 53%, 89%; 65%, 88%; 77%, 74%; and 69%, 79%,
      respectively. These values were 70%, 89%, 88%, 74% and 79% when MRI and MRSI were
      combined. Site-by-site analysis of MRI and MRSI findings and biopsy results
      yielded no significant correlation. CONCLUSIONS: The combination of MRSI and MRI
      provides a significantly higher specificity in the detection of tumours as
      compared with MRI alone and can be recommended as a problem-solving modality
      before biopsy in patients with high PSA levels and suspicious TRUS.

PMID- 16623303
TI  - Utility of computed tomography (CT) and of fine needle aspiration biopsy (FNAB)
      in early diagnosis of fungal pulmonary infections. Study of infections from
      filamentous fungi in haematologically immunodeficient patients.
AB  - PURPOSE: The purpose of this study was to evaluate the sensitivity of
      percutaneous computed tomography (CT)-guided lung biopsy in the early diagnosis
      of fungal pulmonary infections. MATERIALS AND METHODS: Between 1997 and 2003, 18
      haematologically immunodeficient patients with suspected filamentous fungi
      infection and negative bronchoalveolar lavage (BAL) underwent percutaneous
      pulmonary biopsy to diagnose the nature of the infection. In all cases, infection
      developed during the post-chemotherapy bone marrow aplasia period. RESULTS:
      Thirteen out of 18 patients had histologic findings positive for fungal
      infection: 8 Aspergillus and 5 Mucor. In 3 cases, biopsy was not specific, and in
      one case, the tissue sample was inadequate for a diagnosis; however, clinical
      course and response to drugs were compatible with fungal infection. In one
      patient, biopsy was positive for bronchoalveolar carcinoma. The sensitivity of
      percutaneous CT-guided biopsy was 80% and its positive predictive value was 100%.
      We only had one pneumothorax as a complication. CONCLUSIONS: Percutaneous CT
      guided lung biopsy is an easy, safe and reliable procedure to obtain diagnostic
      material. Histological discrimination between Aspergillus and Mucor is important
      in order to plan the correct therapeutic protocols, as Mucor is usually resistant
      to azoles.

PMID- 16623304
TI  - Supraspinatus tendon US morphology in basketball players: correlation with main
      pathologic models of secondary impingement syndrome in young overhead athletes.
      Preliminary report.
AB  - PURPOSE: The purpose of this study was to investigate supraspinatus tendon
      sonographic morphology in a population of young overhead athletes in correlation
      with main pathologic models of secondary shoulder impingement syndrome. SUBJECTS
      AND METHODS: Between April and May 2004, 20 subjects (ten professional basketball
      players and ten non-athlete controls of the same age, weight and height ranges)
      underwent bilateral, standardised, sonographic sholulder examination to evaluate
      supraspinatus echotexture, supraspinatus and subacromial bursa thickness,
      subacromial space width (cutoff of 7 mm) and dynamic anterior impingement beneath
      the acromial margin. RESULTS: All subjects were right handed. No symptomatic
      controls were found. Four players showed signs and symptoms of right atraumatic
      shoulder instability (two cases) or supraspinatus impingement with anterior pain
      (one right and one left shoulder). Subacromial space width was reduced in five
      right-dominant players' shoulders (three symptomatic and two asymptomatic) versus
      zero controls (p<0.05) and in eight players' shoulders versus zero controls on
      total shoulders (p<0.05). No other significant differences were observed between
      the two groups in sonographic parameters considered. CONCLUSIONS: Despite the
      study limitations, ultrasonography (US) is able to detect subacromial space
      narrowing in young overhead athletes as early shoulder impingement sign,
      according to the continuum impingement-instability pathologic model.

PMID- 16623305
TI  - One-shot CT and MR arthrography of the shoulder with a mixture of iodinated and
      paramagnetic contrast agents using arthroscopy as a gold standard.
AB  - PURPOSE: Our aim was to perform computed tomography arthrography (CTA) and
      magnetic resonance arthrography (MRA) of the shoulder as a one-shot examination
      and to evaluate its value on the basis of arthroscopy as a gold standard.
      MATERIALS AND METHODS: Fifteen men and 16 women with planned arthroscopy for
      chronic (n=17) or traumatic tear of the rotator cuff (n=8), congenital atraumatic
      (n=1) or traumatic glenohumeral instability (n=2), traumatic tear of the rotator
      cuff with glenohumeral instability (n=1), or "frozen shoulder" (n=2) underwent
      plain helical CT in neutral position and intra-articular CT-guided injection of a
      mixture of iodinated and paramagnetic contrast agents (gadodiamide at 1:250 and
      iobitridol 350 at 1:5 in 20 ml of saline solution). CT helical scans in intra-
      and extrarotation and T1-weighted MRA scans in the neutral position were
      obtained. CTA and MRA were evaluated separately and jointly (CTA-MRA) in
      different blinded sessions, giving a 0-3 score to the agreement of CTA, MRA, and
      CTA-MRA with arthroscopy. RESULTS: The injected volume of the solution ranged
      from 10 to 24 ml. No side effects were observed. CTA obtained a score of 2.33+/
      0.62, MRA 2.47+/-0.52, and CTA-MRA 2.67+/-0.49. Significant differences were
      found for CTA-MRA versus CTA (p=0.0281) and MRA (p=0.0277). There was no
      significant difference for CTA versus MRA. CONCLUSIONS: CTA and MRA can be
      performed as a one-shot exam. CTA-MRA seems to give more information than CTA or
      MRA separately.

PMID- 16623306
TI  - Angiosonography in suspicious breast lesions with non-diagnostic FNAC: comparison
      with power Doppler US.
AB  - PURPOSE: The purpose of this study was to evaluate the accuracy of
      angiosonography in comparison with colour Doppler ultrasound (US) in the
      discrimination of suspicious breast lesions with nondiagnostic fine-needle
      aspiration cytology (FNAC). MATERIALS AND METHODS: Pre-operative Power Doppler US
      and angiosonography were prospectively performed in 20 suspicious breast lesions
      with non-diagnostic FNAC. A second-generation US contrast agent was utilised with
      a high-frequency transducer and a contrast-specific algorithm (low acoustic
      pressure CnTI). The enhancement characteristics of all lesions were analysed
      using qualitative and quantitative parameters obtained from time-intensity curves
      with the different imaging modalities. The final diagnosis was confirmed at
      pathology in all cases. Microvessel density (MVD) was assessed in the surgical
      specimen using CD34. RESULTS: The correct assessment of biological behaviour was
      achieved in all cases by angiosonography (sensitivity of 100%; specificity of
      91%) and colour Doppler US (45% sensitivity; 78% specificity). MVD correlated
      with the biological behaviour. CONCLUSIONS: Angiosonography is more accurate than
      colour Doppler US in the correct assessment of biological behaviour of suspicious
      breast lesions.

PMID- 16623307
TI  - MR angiography versus intra-arterial digital subtraction angiography of the lower
      extremities: activity-based cost analysis.
AB  - PURPOSE: The aim of this study was to analyse the costs pertaining to the
      radiology department of magnetic resonance angiography (MRA) and intra-arterial
      digital subtraction angiography (DSA) in the evaluation of arterial disease of
      the lower limbs. MATERIALS AND METHODS: The differential cost of the two
      procedures, i.e. the sum of equipment costs (amortisation and service contract),
      variable costs (supplies and related services) and personnel costs (radiologist,
      radiographer and nurse) was determined. The common cost (auxiliary personnel and
      indirect internal costs) was also calculated. Finally, the full cost of the two
      procedures was obtained (sum of differential and common costs). RESULTS: The
      differential cost of MRA was 186.14 euro (equipment costs: 50.80 euro, variable
      costs: 75.04 euro, personnel costs: 60.30 euro) while the differential cost of
      intra-arterial DSA was 238.18 euro (equipment costs: 57.60 euro, variable costs:
      90.13 euro, staff costs: 90.45 euro). The estimated common cost was 5.62 euro.
      Therefore, the full cost of MRA was 191.76 euro and the full cost of intra
      arterial DSA was 243.80 euro (27.1% higher). DISCUSSION AND CONCLUSIONS: Intra
      arterial DSA costs more than MRA, mainly because of the higher costs of supplies
      used during the procedure and higher personnel costs (as a result of the longer
      duration of intra-arterial DSA). It should be noted that our evaluation considers
      costs pertaining to the radiology department only. It is evident that an economic
      analysis considering hospital costs as well would result in much higher costs for
      DSA if post-procedure hospitalisation is required. Our results cannot be simply
      exported to other radiology departments since they refer to the technology and
      organisation adopted in our department. However, our cost analysis model can be
      easily applied to other environments. MRA provides good diagnostic accuracy in
      the evaluation of arteries of the lower extremities, and its biological cost is
      far lower than that of intra-arterial DSA (MRA is noninvasive, it does not use
      ionising radiation, and the contrast medium is safe). Its lower cost is another
      argument in favour of the use of MRA instead of intra-arterial DSA in the
      evaluation of lower-extremity arterial disease.

PMID- 16623308
TI  - Endovenous laser therapy of the incompetent great saphenous vein.
AB  - PURPOSE: The aim of this study was the development of a new, even less invasive
      technique, for the treatment of varicose veins of the lower limbs than
      traditional surgery (ligation with stripping of the saphenous vein). MATERIALS
      AND METHODS: The new interventional radiological procedure uses the 810- to 980
      nm endovascular laser fibre proposed by Min et al. Our technique involves the
      superselective catheterisation of the great saphenous vein under fluoroscopy with
      contralateral venous access achieved by performing iliac crossover. Retrograde
      and anterograde phlebographies are performed with a needle cannula positioned in
      the dorsum of the foot. This enables accurate venous mapping during the procedure
      of laser photothermolysis. We treated 52 patients between June 2003 and June
      2004, with a percentage of recanalisation of 7.5% at 1 year. RESULTS AND
      CONCLUSIONS: The contralateral approach allows greater control over the entire
      procedure, with a reduction in potential risks in relation to the saphenofemoral
      junction given that, unlike in the technique proposed by Min et al. the tip of
      the laser is directed at all times towards the saphenous vein and never towards
      the femoral vein. This more radical procedure offers a significant reduction in
      the possibility of relapse of varicose disease of the saphenofemoral junction.

PMID- 16623310
TI  - Functional MRI in the assessment of cortical activation in subjects with
      Parkinson's disease.
AB  - PURPOSE: The purpose of this study was to evaluate cortical activation patterns
      in patients with Parkinson's disease during a relatively complex motor task.
      MATERIALS AND METHODS: Seven patients (six men and one woman) with lateralised
      akinetic-rigid Parkinson's disease underwent functional magnetic resonance
      imaging (MRI) of the brain with a 1.5-T magnet. Finger tapping was chosen as a
      motor task. The control group included 11 volunteers (six men and five women)
      with no neurological disease. RESULTS: Patients showed hyperactivity of the
      ipsilateral and contralateral motor cortex associated with bilateral over
      activation of the parietal cortex during movement of the affected hand. In some
      cases, there was a lack of activation of the pre-motor and supplementary motor
      areas whereas, when present, activation in these areas was greater during
      movement of the healthy hand. Finally, activation of the occipital cortex was
      found in all patients as a result of their tendency to control movement visually.
      CONCLUSIONS: Results of this study confirm a re-organisation of cortical circuits
      due to subcortical damage in patient's with Parkinson's disease.

PMID- 16623309
TI  - Doppler ultrasound and contrast-enhanced magnetic resonance angiography in
      assessing carotid artery stenosis.
AB  - PURPOSE: This study prospectively compares Doppler ultrasound (Doppler US) and
      contrast-enhanced magnetic resonance angiography (CE-MRA) with digital
      subtraction angiography (DSA) and endarterectomy findings to determine the
      accuracy in assessing carotid artery stenosis. MATERIALS AND METHODS: Thirty-two
      patients underwent carotid endarterectomy, 21 studied with Doppler US, CE-MRA and
      DSA and 11 with Doppler US and CE-MRA. In 41 carotid arteries, the degree of
      stenosis was analysed with Doppler US and CE-MRA and compared with DSA by using
      the Spearman rank correlation coefficient. Nine out of 32 endarterectomies were
      done using the eversion technique, and it was possible to compare Doppler US, CE
      MRA and DSA with the specimen measurement. Twenty-three out of 32
      endarterectomies were done using the standard technique, and the presence of
      ulcers was documented. RESULTS: There was a significant Doppler US/DSA (Rs=0.86;
      p<0.001) and CE-MRA/DSA (Rs=0.81; p<0.001) correlation for the degree of
      stenosis. The diagnostic accuracy of the three methods was the same (89%). Ulcers
      were most frequently seen at CE-MRA, with a diagnostic accuracy of 85%.
      CONCLUSIONS: These data suggest that endarterectomy on the basis of Doppler US
      and CE-MRA can be considered appropriate. CEMRA was the best noninvasive imaging
      modality to detect plaque ulceration.

PMID- 16623311
TI  - Dacryocystostenting: technical and long-term results.
AB  - PURPOSE: We describe our experience in treating epiphora caused by chronic
      inflammation and obstruction of the nasolacrimal system by endonasal placement of
      a polyurethane stent in the nasolacrimal duct, with long-term assessment of
      patency (4 years). MATERIAL AND METHODS: Between July 1998 and May 2001, 57
      stents were inserted using Song's technique. All procedures were carried out in
      the radiology suite following mild sedation and local anaesthesia of the
      conjunctival and nasal mucosa. The follow-up investigation concerns 23 stents
      assessed 24-48 months after placement. RESULTS: At follow-up after 4 years, 20
      stents (86.9%) were obstructed. Fifteen of the stents removed underwent
      histological analysis that showed occlusion of the stent with granulation tissue
      (eight cases), necrotic material (four cases) and fibrosis (three cases).
      CONCLUSIONS: Although encouraging in terms of safety, simplicity and
      reproducibility, the results obtained with the polyurethane stent demonstrate
      poor long-term efficacy and stimulate the search for new strategies such as
      programmed stent removal or the development of a more biocompatible material.

PMID- 16623312
TI  - Dynamic swallowing study and radiation dose to patients.
AB  - PURPOSE: The purpose of this study was to define an optimal radiological
      procedure to evaluate the results of rehabilitation therapy for swallowing
      disorders and to calculate both the effective and organ dose to the patient to
      provide a measure of the radiation risk associated with the procedure. MATERIALS
      AND METHODS: In order to define the optimal radiological procedure, kerma-area
      product (KAP) measurements and evaluations of image quality in fluoroscopy and
      fluorography mode were made using dedicated phantoms. Twenty-two patients were
      included in the study, and the values of KAP, screening time and average voltage
      selected were individually recorded. The recorded KAP values were used to
      estimate radiation risk with the use of dedicated calculation software. RESULTS:
      Median, first and third quartiles of the KAP distribution were, respectively,
      2.1, 1.5 and 2.7 Gy cm2, with a corresponding effective dose of 0.35, 0.26 and
      0.46 mSv. A good correlation between KAP and exposure time was also found
      (R2=0.85). Exposure of the thyroid, which is inside the radiation field, accounts
      for the greatest share to the effective dose, with a calculated median dose of 6
      mGy. CONCLUSIONS: With the defined radiological procedure, the obtained KAP
      values are lower than recorded doses in interventional radiology, and the
      corresponding values of entrance skin dose are lower than the threshold dose for
      deterministic effects. Considering the effective dose at the median KAP value,
      the probability for stochastic effects is shown to be low, at approximately 1 in
      39,000.

PMID- 16623313
TI  - Multidetector CT and dentascan software: dosimetric evaluation and technique
      improvement.
AB  - PURPOSE: The development of new operative techniques in oral and maxillofacial
      surgery within the last few years has led to an increasing demand for Dentascan
      examination, also in paediatric patients. It is necessary to modify acquisition
      parameters to reduce the absorbed dose. The aim of this study was to define a
      Dentascan protocol in which a reduced X-ray dose could be used. MATERIALS AND
      METHODS: Dosimeters were applied to the eyes, mouth, parotid glands, thyroid and
      back of the neck of an anthropomorphic Plexiglas phantom that underwent
      multidetector computed tomography (MDCT) Dentascan examinations. Both 120kV and
      80 kV were used to study the mandibular and maxillary arches. RESULTS:
      Examinations obtained with the 80 kV protocol showed a ten-fold reduction in the
      absorbed dose, without affecting image quality. CONCLUSIONS: We suggest a
      Dentascan protocol that reduces the X-ray dose administered to the patient while
      ensuring the same high diagnostic accuracy.

PMID- 16623314
TI  - Determining the impact of a surgical liaison nurse role in the paediatric
      operating room.
AB  - A two-group (N = 92) quasi-experimental pre-post test design was used to examine
      the effects of intra-operative communication by a surgical liaison nurse (SLN) on
      parental anxiety. Group I received in person progress reports from the SLN. Group
      II received routine perioperative care. The Speilberger's State-Trait Anxiety
      Inventory (STAI) Scale and investigator developed family rating scales were
      distributed to both groups and used as a quantitative as well as a qualitative
      approach to determine what was helpful for the family members during the
      operative period. Two hundred and eighty feedback forms were dispersed to various
      health care professionals including all anaesthetists, surgeons, nurses and other
      staff in the perioperative care team, including the operating room, day surgery
      unit and the post anaesthetic recovery room areas. Feedback forms were also
      circulated to staff from the intensive care unit and the surgical in-patient
      units. The results showed the anxiety levels were lower for the families who
      received in person progress reports but the difference by group was not
      statistically significant. Thematic written responses provided examples of
      improved care and effective time management behaviours on the part of the health
      care professionals. Written responses provided validation for the scale scores
      for both families and health care professionals and were an indication of the
      support for the role of the surgical liaison nurse. Qualitative findings implied
      that the surgical liaison nurse facilitated the transfer of necessary information
      between the perioperative care team and the family thus providing a support
      mechanism for families under stress.

PMID- 16623315
TI  - LEADERNOMICS. Situational balance--one size does NOT fit all!
AB  - Leadernomics involves effectively blending each of the styles of leadership in a
      balance that is best suited for each situation, individual, or group. An
      excellent leader will be able to rapidly analyze the situation and incorporate
      the strategies that will be most effective.

PMID- 16623316
TI  - The Canadian introduction to the Greenlight laser.
AB  - The Greenlight laser--a high powered laser used for Benign Prostate Hyperplasia-
      was used for the first time in Canada in Newmarket, Ontario by Dr. Liquornik BSc
      MDCM FRCSC in 2003. The laser is proving to eliminate hospital stay, decrease the
      catheter indwelling time from one week to less than 28 hours, decrease pain and
      suffering and make repeat procedures something rare. The laser melts away the
      prostate and leaves a urethra that is unscathed by the effects of the laser
      because the beam concentrates on the overgrown prostatic tissue only. The
      patients are very satisfied and back to normal routines in one to two days.

PMID- 16623317
TI  - Corticobulbar tracts.

PMID- 16623318
TI  - Head-eye movement control model based on genetically selected neural network.

PMID- 16623319
TI  - Eye and eyelid movements during blinking: an eye blink centre?

PMID- 16623320
TI  - 3D brainstem topodiagnosis--a voxel-based model analyzing MR imaging data.

PMID- 16623321
TI  - Functional activity mapping of brainstem nociceptive networks in animals.

PMID- 16623322
TI  - Brainstem functional imaging in humans.

PMID- 16623323
TI  - Laboratory and clinical investigations of the region of the rostral brainstem in
      motor control.

PMID- 16623324
TI  - Functional properties of brainstem motoneurons following their reinnervation of
      native or foreign muscles.

PMID- 16623325
TI  - The effects of a prepulse on the StartReact phenomenon.

PMID- 16623326
TI  - Trigemino-cervical reflexes: clinical applications and neuroradiological
      correlations.

PMID- 16623327
TI  - What the vestibulo-spinal system does and what it doesn't.

PMID- 16623328
TI  - Investigation of brainstem: descending pain modulation in animals and humans.

PMID- 16623329
TI  - Neuropathic facial pain.

PMID- 16623330
TI  - Diagnosis of trigeminal neuralgia: a new appraisal based on clinical and
      neurophysiological findings.

PMID- 16623331
TI  - Pain and itch in Wallenberg's syndrome: anatomical-functional correlations.

PMID- 16623332
TI  - Long-term depression of orofacial somatosensory processing.

PMID- 16623333
TI  - Laser evoked potentials in primary headaches: a possible clinical or research
      tool?

PMID- 16623334
TI  - The startle reflex, voluntary movement, and the reticulospinal tract.

PMID- 16623335
TI  - Auditory startle responses as a probe of brainstem function in healthy subjects
      and patients with movement disorders.

PMID- 16623336
TI  - Neurophysiological aids to the diagnosis of progressive supranuclear palsy (PSP).

PMID- 16623337
TI  - Recent findings in cranial and cervical dystonia: how they help us to understand
      the pathophysiology of dystonia.

PMID- 16623338
TI  - Two physiological aspects of the electrically elicited blink reflex: motor unit
      potentials recruitment and levator palpebrae inhibitory components.

PMID- 16623339
TI  - Neurovascular conflict and hemifacial spasm.

PMID- 16623340
TI  - [Behcet's disease and the possibilities of modern tumour necrosis factor
      inhibiting medication].
AB  - A 25-year-old woman was admitted after having had a fever for one month,
      headache, nausea, vomiting, dysarthria and right-sided hemiparesis. A 35-year-old
      man was admitted because of severe loss of vision and a history of focal
      retinochoroiditis. Both were suffering from Behcet's disease. Behcet's disease
      can present with systemic symptoms that might be related to aberrant T-cell
      functions. It is treated with a variety of immunoregulatory drugs. Recently,
      treatment with tumour necrosis factor (TNF) alpha-inhibiting molecular designed
      drugs such as infliximab or etanercept has improved the therapeutic prospective
      of Behcet patients. Both of the patients described above developed refractory
      disease and responded to treatment with these new drugs.

PMID- 16623341
TI  - [The dangers to health of fine dust particles in the air].
AB  - Many scientific studies have been published that connect all kinds of
      toxicological characteristics offine dust particles, measured in vitro, with lung
      damage parameters both in animals and humans. These studies do not provide an
      unequivocal picture on the mechanisms that are responsible for the perceived
      connection between exposure to fine dust and the degree of illness and death.
      Without connecting to specific sources of air pollution, this type of study
      moreover, is only of limited value for drawing up control policy. Even if one or
      more responsible properties could be determined, it is still unlikely that these
      would be translated into a standard for permitted levels of concentration in the
      open air. It is far more likely that such insight will be used for specific
      source policy aimed at tackling the sources that contribute the most to the
      harmfulness of the mixture of air pollution.

PMID- 16623342
TI  - [The practice guideline 'Urinary-tract infections' (second revision) from the
      Dutch College of General Practitioners; a response from the perspective of
      general practice].
AB  - The Dutch College of General Practitioners recently published an update of the
      practice guideline on urinary-tract infections. This guideline provides a clear
      overview of the medical history, the diagnostic methods and the treatment
      options. Sixteen management modalities are presented in relation to specific
      patient characteristics. However, this revised guideline warrants some minor
      comments. According to the guideline, the dipstick (nitrite) test and dipslide
      form the two cornerstones of the diagnosis of urinary-tract infections. The value
      of the dipslide, however, seems to have been overestimated and that of
      microscopic examination of the urine by skilled physicians to have been
      underestimated. New in this guideline compared to that of 1999 is that
      nitrofurantoin (the treatment of first choice in uncomplicated infections) should
      be given for five instead of three days. The guideline motivates this change in
      policy on the basis of the numerous treatment failures seen in practice. The most
      convincing type of evidence, however, is not available due to the lack of
      relevant randomised clinical trials. The introduction of the prescription of
      phosphomycin, which is unusual in the Netherlands, as an alternative treatment
      for uncomplicated infections requires supportive evidence before it will be
      accepted by general practitioners. This well-documented guideline provides clear
      guidance for the general practitioner faced with patients with urinary-tract
      symptoms that could be caused by infection.

PMID- 16623343
TI  - [The practice guideline 'Urinary-tract infections' (second revision) from the
      Dutch College of General Practitioners; a response from the perspective of
      urology].
AB  - The convenient and clearly organised structure of this second revision of the
      practice guideline on urinary-tract infections from the Dutch College of General
      Practitioners provides a clearly described role for the general practitioner in
      the diagnosis and treatment of such infections. Most striking is the change in
      the classification of diagnostic patient categories. It seems that pregnant women
      with urinary-tract infections represent an important group in extramural
      medicine. This revised guideline shows great promise for ensuring efficient and
      effective routing of the various patient groups presenting with urinary-tract
      infections at the office of the general practitioner.

PMID- 16623344
TI  - [Summary of the practice guideline 'Urinary-tract infections' (second revision)
      from the Dutch College of General Practitioners].
AB  - The 1999 practice guideline 'Urinary-tract infections' from the Dutch College of
      General Practitioners has been revised. Not only febrile urinary-tract infections
      are now regarded as 'complicated', but also all urinary-tract infections in men,
      pregnant women, children, and patients with kidney or urinary-tract disease,
      impaired immune response or an indwelling catheter. Under certain conditions, in
      women recognising the symptoms of an earlier uncomplicated urinary-tract
      infection, treatment may be instituted without performing supplementary
      urinalysis. The nitrite dipstick test and dipslide culturing are recommended for
      the diagnosis of urinary-tract infections; the value of the leukocyte esterase
      dipstick test is limited. A group-B streptococcal urinary-tract infection during
      pregnancy is an indication for intravenous antibiotic prophylaxis during the
      delivery. The recommended duration of treatment with nitrofurantoin is extended
      from three to five days. Both increased bacterial resistance to trimethoprim and
      the intention to reduce the use of fluoroquinolones in the treatment of
      uncomplicated urinary-tract infections were reasons for including phosphomycin in
      the guideline. In addition to antibiotic prophylaxis, cranberry products may be
      of value in the prevention of recurrent urinary-tract infections.

PMID- 16623345
TI  - [Coeliac plexus block in patients with pancreatic tumour pain].
AB  - Pancreatic cancer tends to be diagnosed at a relatively late stage of the disease
      when curative resection is precluded. In view of the poor prognosis and the
      severe pain, palliative care should be aimed at providing adequate pain relief
      and optimal quality of life. Pancreatic cancer pain is primarily treated by the
      combination of NSAIDs, adjuvant analgesic drugs, and oral or transdermal opioids.
      The neurolytic coeliac plexus block is recommended as adjuvant therapy for the
      palliative treatment of pancreatic cancer pain. In addition quality of life,
      especially functional and physical aspects, is significantly improved in patients
      following a coeliac plexus block. The most common approach to the coeliac plexus
      is the percutaneous posterior technique. Serious complications that may follow
      application of this technique include sensory disorders, muscle weakness and
      paraparesis. More recently, new techniques such as thoracoscopic splanchnicectomy
      and endoscopic ultrasound-guided coeliac plexus block have emerged as efficient
      alternatives in terms of pain relief and quality-of-life improvement. The
      neurolytic coeliac plexus block has become a well-developed method of pain relief
      in patients with pain resulting from malignancies of the pancreas. To define the
      role of these new techniques in the palliative treatment of pancreatic cancer
      pain, comparative studies regarding efficacy, side effects, and complications
      have to be performed.

PMID- 16623346
TI  - [Diagnostic image (268). A man with 'pyodermia' in the beard area].
AB  - A 61-year-old man developed tinea barbae (kerion barbae) caused by Trichophyton
      mentagrophytes varietas interdigitale following prolonged intensive care
      treatment for septic shock and meningitis. Whenever a suppurative folliculitis
      develops, fungal infection is a possible cause.

PMID- 16623347
TI  - [Complications within 30 days following placement of a carotid stent with
      cerebral protection in patients with considerable symptomatic carotid stenosis;
      Erasmus MC, Rotterdam, 1999-2004].
AB  - OBJECTIVE: To describe the complications that occur within 30 days following the
      placement of a stent in the carotid artery in patients with considerable
      symptomatic carotid stenosis. DESIGN: Retrospective. METHOD: Data were collected
      on 98 patients who received a carotid stent due to symptomatic carotid stenosis
      of > or = 70% of the lumen at the Erasmus MC, Rotterdam, the Netherlands, in the
      years 1999-2004. A filter, distal occlusion balloon or the Parodi anti-embolism
      system was used to prevent cerebral embolism. Outcome measures were complications
      within 30 days following intervention. RESULTS: Four patients were excluded in
      the period between diagnosis and stenting. Major complications occurred in 3
      patients: 1 died due to cerebral haemorrhage and 2 experienced cerebral
      infarction. Transient neurological complications occurred in 4 patients who
      recovered completely. Dissection of the renal artery occurred in 1 patient, which
      necessitated a stent. Vascular damage of the internal carotid artery was not
      observed in any patient. The 3 major adverse events and 3 of the 4 minor adverse
      events occurred in the first 47 patients treated. None of the last 47 patients
      treated developed major adverse events.

PMID- 16623348
TI  - [Relationship between the composition of fine dust particles in the air and lung
      function in school children].
AB  - OBJECTIVE: To determine whether or not there is a relationship between the lung
      function of school children and the ability of fine dust particles in the air to
      generate radicals. DESIGN: Descriptive. METHOD: Six primary schools in locations
      with different traffic volumes were selected in Maastricht, the Netherlands. Air
      samples were taken in these schools over a period of 4 days; the concentration of
      fine dust was measured in the 6 pooled samples. Lung function tests were
      performed in children in the age of 8-13 and their parents filled out a
      questionnaire on the state of their children's health. RESULTS: An average of 66%
      of the children (184 girls and 158 boys, with an average age of 10 years (range:
      8-13 years)) participated. The average FEV1 for the children from the 6 schools
      was not related with the total amount of fine dust particles in the air. However,
      a lower average FEV1 was associated with a higher radical-generating capacity in
      the air samples. No direct association was observed between the radical
      generating capacity of the dust and the traffic intensity. CONCLUSION: There was
      a clear relationship between lung function and the radical-generating capacity of
      fine dust in the air. On the basis of these findings future guidelines could be
      based on chemical properties of the fine dust particles and not exclusively on
      the quantity of fine dust.

PMID- 16623349
TI  - [The first newborn with congenital rubella syndrome during the rubella epidemic
      in The Netherlands in 2004/'05].
AB  - A newborn male was diagnosed with congenital rubella syndrome. His 31-year-old
      mother had had erythematous exanthema during a period of amenorrhea lasting 7
      weeks; she was not vaccinated and had never had a rubella infection. The
      infection was confirmed serologically. The mother gave birth to an icteric,
      microcephalic, dysmature neonate with hepatosplenomegaly and exanthema with
      multiple, small purple-red spots. Ultrasound cardiography revealed a persistently
      open arterial duct and a small defect of the ventricular septum. Radiological
      evaluation of the long bones showed the characteristic longitudinal lucent
      strands ('celery stalk appearance'). Ultrasound of the cerebrum showed diffuse
      widespread calcifications in the white matter and basal ganglia, striatal
      vasculopathy and diffuse parenchymal disorders. Psychomotor development was
      impaired. The patient was completely deaf in the left ear and had severely poor
      hearing in the right ear. After the introduction of the rubella vaccine in the
      Netherlands in 1974 a substantial decrease was seen in the incidence of rubella
      infections as well as congenital rubella syndrome. An epidemic of rubella
      infections has been present within the non-vaccinated population since September
      2004. Recognition of the clinical symptoms and confirmation of the clinical
      suspicion with proper viral diagnostic methods are needed to control the current
      epidemic and to prevent secundary spread. Infants born with congenital rubella
      syndrome remain infectious to non-vaccinated individuals for a prolonged period
      of time; the virus is excreted in the urine and faeces. Long-term medical follow
      up is necessary because the congenital rubella infection can cause abnormalities
      after the neonatal period.

PMID- 16623350
TI  - [Fracture of the femoral neck in bed caused by an epileptic seizure].
AB  - An 82-year-old man was brought into the emergency department after an epileptic
      seizure. Although the seizure took place in his bed and was not followed by a
      fall, his right hip was broken. No underlying bone abnormalities were found. The
      patient received a femoral head & neck prosthesis and recovered fully. Fractures
      are more common in patients with epilepsy than in the general population, due to
      both seizure-related trauma and a relatively high prevalence of osteoporosis,
      which is due partly to the use of anti-epileptic drugs. However, even after a
      seizure without trauma in a patient without underlying abnormalities of bone
      structure, a fracture may arise as a result of the force of the muscle
      contractions during the seizure.

PMID- 16623351
TI  - [Legal and practical aspects of perinatal death].
AB  - There is some debate as to whether the Dutch Burial Act applies to neonatal
      deaths after a gestation of less than 24 weeks. It is recommended that the Act be
      considered applicable in these situations, leading to a compulsory (external)
      post mortem examination, the issue of an official death certificate, and
      registration of the birth and death at the official registry office, followed by
      burial or cremation according to the law. The Act should be amended to this
      effect. It is also recommended that the Burial Act no longer apply in cases of
      known intra-uterine death before 24 weeks of gestation where birth takes place
      after 24 weeks. The stipulated cut-off point in the Act for defining a
      miscarriage as opposed to a birth or stillbirth, i.e. 24 weeks of gestation,
      should preferably be replaced by the international (WHO) criterion of a birth
      weight of 500 g, as this will lead to less ambiguity and a better comparison of
      Dutch and international data concerning perinatal mortality.

PMID- 16623352
TI  - [Incidental cystic structures in the upper abdomen: to remove or not to remove?].

PMID- 16623354
TI  - Acute heart failure: definition, etiology and importance.

PMID- 16623353
TI  - Acutely decompensated heart failure: characteristics of hospitalized patients and
      opportunities to improve their care.
AB  - Heart failure (HF) remains a major public health problem in western countries,
      despite the enormous progress in its diagnosis and treatment. Acute and chronic
      decompensated HF are leading medical causes of hospitalization among people aged
      over 65 years in European countries, the USA, Australia and New Zealand. However,
      there have been few studies on acute and chronic decompensated HF and the
      European Society of Cardiology (ESC) guidelines on this subject have only just
      been published. AIM: To evaluate the overall prevalence of hospitalization due to
      HF according to its subtypes, comorbidities, and decompensating factors, in the
      Medical Department of a central teaching hospital in an urban area. METHODS: We
      performed a retrospective observational study of patients admitted consecutively
      to the Medical Department via the emergency room between January and June 2001.
      Discharge casenotes on 1038 admissions were reviewed. Those with a diagnosis of
      HF or cardiovascular conditions associated with or precursors of HF were
      analyzed. Cases with a final diagnosis of HF according to the criteria of the ESC
      guidelines were included in the study. We evaluated the overall prevalence of HF
      and subtypes of cardiac dysfunction, etiological risk factors, patients'
      demographic characteristics, decompensating factors, comorbidity, mean length of
      hospital stay, and in-hospital mortality rate. RESULTS: We identified 180
      patients with HF (17.4%), mean age 74.6 +/- 14; 87 were male (48%), aged 73.7 +/-
      14.2, and 93 female (52%), aged 75.6 +/- 14. Left ventricular systolic
      dysfunction (LVSD) was present in 42.2% of cases, preserved left ventricular
      systolic function in 32.6%, and valvular heart disease in 10.6%. Hypertension and
      coronary artery disease were the main etiological risk factors (62.2% and 42.8%
      respectively). Atrial fibrillation was recorded in 43.4% of the patients,
      diabetes was diagnosed in 21.6%, and anemia and chronic obstructive pulmonary
      disease in about one third. Infection, predominantly respiratory, was the main
      factor triggering decompensation, followed by uncontrolled hypertension and
      supraventricular tachyarrhythmia. At admission, 42.2% of the patients were in
      NYHA class III and 44.8% in NYHA class IV. HF patients had a mean hospital stay
      of 13.8 days, slightly shorter than the mean overall stay of patients admitted to
      the Medical Department in the same period (14.5 days). In-hospital mortality for
      HF patients was 7.7%, with HF being the first cause of admission to the Medical
      Department, followed by stroke (10.6%). CONCLUSIONS: This study confirms the high
      prevalence of acute or chronic decompensated HF in patients hospitalized in the
      Medical Department of a central teaching hospital in an urban area. The patients
      were mainly elderly, of both genders, with a slightly higher proportion of HF due
      to LVSD. Most patients were in NYHA classes III and IV. Mean hospital stay was no
      longer than that of all patients admitted in the same period. The in-hospital
      mortality rate was low. The age-group affected and the high prevalence of
      multiple comorbidities emphasize the need to establish HF clinics with
      multidisciplinary teams to manage these patients, and health authorities must be
      made aware of the burden of this syndrome.

PMID- 16623355
TI  - Glucose metabolism in non-diabetic patients with stable coronary artery disease.
AB  - BACKGROUND: Diabetes and other forms of impaired glucose metabolism (IGM) can be
      present in patients with coronary artery disease (CAD), despite normal fasting
      glycemia and no prior evidence of diabetes. Undiagnosed IGM can be associated
      with increased risk of cardiovascular events. OBJECTIVE: To assess the prevalence
      of IGM in patients with CAD and without diabetes and to identify its
      repercussions on their cardiovascular risk profile. METHODS: Consecutive patients
      with CAD documented by angiography, without prior history of diabetes and fasting
      glycemia < 126 mg/dL, were studied. An oral glucose tolerance test (OGTT) was
      performed to identify and classify IGM. The patients were divided into three
      groups: normal if fasting glycemia < 100 mg/dL and normal OGTT; prediabetes if
      fasting glycemia > or = 100 mg/dL and abnormal OGTT, with 2-h glycemia > or = 140
      and < 200 mg/dL; and diabetes if 2-h glycemia > or = 200 mg/dL after OGTT. For
      assessment of the cardiovascular risk profile, various clinical, laboratorial
      (including lipid profile, fasting insulinemia 2 h after OGTT, insulin resistance
      index and A1c hemoglobin) and angiographic characteristics were analyzed. The
      differences between groups were determined. RESULTS: 54 patients were studied
      (mean age 65 +/- 9 years, 78 % male) and IGM was identified in 37 (69%), with
      prediabetes in 23 (43%) and diabetes in 14 (26%). Patients with IGM had more
      dyslipidemia, higher levels of fasting glycemia, triglycerides and urea and lower
      HDL cholesterol. Metabolic syndrome was diagnosed in 12% of patients in the
      normal group, 44% in the prediabetes group and 50% in the diabetes group (p =
      0.047). CAD was more severe in the presence of IGM, being multivessel in 84% of
      these patients versus 59% in the normal group (p = 0.046). CONCLUSION: In
      patients with CAD without clinical suspicion of diabetes, a routine OGTT can
      identify a significant percentage with prediabetes and diabetes, which can have a
      negative impact on their cardiovascular risk profile.

PMID- 16623356
TI  - Ghrelin reverses molecular, structural and hemodynamic alterations of the right
      ventricle in pulmonary hypertension.
AB  - Ghrelin is an endogenous peptide that has a dual effect by activating specific
      receptors and by stimulating release of growth hormone. There is increasing
      evidence that ghrelin has a potent vasodilator effect. Recently, we demonstrated
      that exogenous administration of ghrelin modulates its endogenous levels and
      attenuates the majority of alterations induced by monocrotaline (MCT). In the
      present study, we evaluate the effects of chronic administration of ghrelin on
      hemodynamic and morphometric parameters of the right ventricle, as well as on
      myocardial levels of SERCA2a and endothelin-1. Adult Wistar rats were injected
      with MCT (60 mg/kg, sc) or just the vehicle (day 0). One week later, the animals
      treated with MCT were randomly divided into two groups and treated with ghrelin
      (100 microg/kg, bid, sc) or with a similar volume of vehicle. Between days 21-25
      the animals were instrumented to record right ventricular (RV) pressures and
      samples were collected for morphological and molecular analysis. Ghrelin
      treatment attenuated the effects of MCT, namely: RV myocyte fiber diameter,
      pulmonary vascular remodeling (evaluated by % medial wall thickness of peripheral
      arteries), RV peak systolic pressure, RV end-diastolic pressure, time constant
      tau, and SERCA2a and endothelin-1 mRNA levels. Chronic ghrelin administration
      attenuates MCT-induced pulmonary hypertension, vascular remodeling and RV
      hypertrophy. These results suggest a potential therapeutic role for the ghrelin
      growth hormone axis in pulmonary hypertension.

PMID- 16623357
TI  - The value of NT-proBNP in early risk stratification of acute coronary syndromes.
AB  - INTRODUCTION: The N-terminal portion of brain natriuretic peptide (NT-proBNP) has
      been identified as an indicator of prognosis in different cardiovascular
      diseases. Its role in risk stratification in patients with acute coronary
      syndromes (ACS) is still under evaluation. OBJECTIVE: We aimed to evaluate the
      prognostic value of NT-proBNP measured in the first 48 hours after admission due
      to an acute coronary syndrome. METHODS: Our study included 142 patients (aged
      62.7 +/- 12.0 years, 70.4% males) admitted to a cardiology unit with an ACS. All
      laboratory evaluations were performed in the first 48 hours after admission. The
      mean follow-up was 200 days. Death from any cause or hospitalization because of a
      major acute cardiovascular event (whichever occurred first) was defined as the
      end-point. RESULTS: Cardiovascular risk factors were found in a significant
      proportion of our sample (hypertension in 56.3%, diabetes mellitus in 38.0%,
      current or previous smoking in 51.4%, dyslipidemia in 67.6%). Fifty-eight
      patients had left ventricular systolic dysfunction (LVSD). Serum levels of NT
      proBNP were 2174 +/- 4801 pg/ml. Variables associated with event-free survival in
      univariate analysis were: NT-proBNP (HR 1.007, 95% CI 1.003-1.011, for each 100
      pg/ml increment), serum glucose (hazard ratio [HR] 1.007, 95% CI 1.001-1.012, for
      each 1 mg/dl increment) and maximum cardiac troponin I (cTnI) level (HR 1.005,
      95% CI 1.001-1.009, for each 1 ng/ml increment). The white blood count (WBC) was
      marginally associated with a poor prognosis (HR 1.152, 95% CI 0.994-1.335, for
      each 1000/mm3 increment). After adjustment for the above variables, age, sex,
      left ventricular systolic dysfunction, diabetes, coronary anatomy and coronary
      revascularization using a forward likelihood ratio Cox regression model, NT
      proBNP remained the only variable with significant prognostic value (HR 1.007,
      95% CI 1.003-1.011, for each 100 pg/ml increment). CONCLUSIONS: These data
      suggest that NT-proBNP is a strong clinical predictor of prognosis in acute
      coronary syndromes. Its early measurement should be included in the risk
      stratification strategy in this setting.

PMID- 16623358
TI  - Rupture of a congenital aneurysm of the non-coronary sinus of Valsalva into the
      right atrium.
AB  - We present the case of a patient evaluated for a continuous murmur, in which a
      ruptured congenital sinus of Valsalva aneurysm with fistulization to the right
      atrium was demonstrated by echocardiography. The authors review the relevant
      clinical features of this entity.

PMID- 16623359
TI  - Analgesia, sedation and neuromuscular blockade in mechanically ventilated cardiac
      intensive care unit patients. Part I: Analgesia.
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- 16623360
TI  - How to design a clinical in cardiology. The main issues.
AB  - Accumulated clinical experience, arising from consecutive observation of
      patients, produces biased evaluations of drug efficacy. Only properly designed
      clinical trials can minimize bias and evaluate drug efficacy. However, clinical
      experience can be useful in clinical trial planning. The authors review the main
      aspects of the methodology of clinical trials in cardiology, namely the different
      phases of clinical research in humans, definition of the population, how to avoid
      bias, design and randomization options, determination of sample size, outcome
      types, and precautions to be taken during follow-up.

PMID- 16623361
TI  - A case of coarctation of the aorta diagnosed at age 75.

PMID- 16623362
TI  - Echocardiographic diagnosis of persistent left superior vena cava.

PMID- 16623363
TI  - Misplaced devices in the chest, abdomen, and pelvis: Part I.
AB  - Numerous medical devices are used in the chest and fewer in the abdomen and
      pelvis. They are frequently seen on various radiological studies in daily
      practice. Knowing the specific name of the device is not important. However,
      knowing the proper positioning and function of the device is necessary. It is a
      duty of the reporting radiologist to recognize the malpositioning or breakage of
      a medical device and to inform the responsible physician promptly, since these
      complications can have undesirable consequences and sometimes a fatal outcome.

PMID- 16623364
TI  - Misplaced devices in the chest, abdomen, and pelvis: Part II.
AB  - Numerous medical devices are used in the chest and fewer in the abdomen and
      pelvis. They are frequently seen on various radiological studies in daily
      practice. Knowing the specific name of the device is not important. However,
      knowing the proper positioning and function of the device is necessary. It is a
      duty of the reporting radiologist to recognize the malpositioning or breakage of
      a medical device and to inform the responsible physician promptly, since these
      complications can have undesirable consequences and sometimes a fatal outcome.

PMID- 16623365
TI  - Drug-induced lung diseases: most common reaction patterns and corresponding high
      resolution CT manifestations.
AB  - Drug-induced lung disease is an increasingly common cause of morbidity and
      mortality. The diagnosis is based on clinical history and consistent radiologic
      findings. Lung biopsy is performed in a small percentage of cases. High
      resolution CT may demonstrate parenchymal abnormalities in patients with normal
      radiographs and provides a better depiction of the pattern and distribution of
      findings. Knowledge of the most common high-resolution CT manifestations and the
      corresponding histologic patterns is important for early recognition and proper
      management of drug-induced lung disease.

PMID- 16623366
TI  - The CT findings of abdominal anticoagulant-related hematomas.
AB  - Spontaneous bleeding is a serious complication of anticoagulation that should be
      promptly recognized and treated. The clinical manifestations vary and are related
      to the site of the hemorrhage. CT, a simple and safe imaging modality, plays an
      important role in the accurate determination of the presence or absence of an
      anticoagulant-related bleed, its extent, and its precise location. This pictorial
      article reviews and demonstrates the CT findings of a variety of anticoagulant
      related hematomas at various anatomical locations in the abdomen.

PMID- 16623367
TI  - CT findings of latrogenic complications following gastrointestinal endoluminal
      procedures.
AB  - Abdominal CT, a simple and safe imaging modality, plays an important role in
      evaluating patients suspected of having abdominal complications following
      nonsurgical gastrointestinal procedures, to accurately determine the presence or
      absence of such insults. This pictorial article reviews and demonstrates the CT
      findings of various complications following upper endoscopy, percutaneous
      endoscopic gastrostomy, endoscopic retrograde cholangiopancreatography,
      endoscopic US, colonoscopy, and enemas (barium as well as cleansing).

PMID- 16623368
TI  - Minimally invasive management of urolithiasis.
AB  - The management of urolithiasis has radically changed over the last two decades.
      Open surgery has been almost completely replaced by minimally invasive
      procedures, mainly extracorporeal shock wave lithotripsy (ESWL) and ureteroscopy
      (URS). Although these treatment modalities have been proven to be very safe and
      effective, serious complications can occur. Prompt diagnosis is often essential
      and may even be lifesaving. Radiologists play an important role in this setting,
      since many of these complications can be readily diagnosed by imaging. Awareness
      of the wide spectrum of complications may be crucial in interpreting imaging
      studies of patients who have undergone one of these procedures. This article
      reviews the contemporary management of ureteric stones with ESWL and URS and
      illustrates the radiological findings of complications of these procedures.

PMID- 16623369
TI  - Abdominal complications of ventriculoperitoneal shunts in children.
AB  - Ventricular peritoneal cerebrospinal fluid shunting has become a common pediatric
      neurosurgical procedure over the last 40 years. While invaluable for these
      patients, shunts are prone to complications, especially in children. Abdominal
      complications are often secondary to infection and its complications, and may be
      difficult to recognize in these medically complex children. Imaging is often
      required, but the findings may be subtle and require an appreciation of the
      spectrum of possible abnormalities. This article reviews the imaging findings
      present with abdominal shunt complications.

PMID- 16623370
TI  - Perforation of the colon and rectum--a newly recognized complication of CT
      colonography.
AB  - CT colonography (CTC) and conventional colonoscopy may have similar efficacy for
      detection of polyps > 6 mm. Perforation of the colon and rectum is a relatively
      rare, but potentially morbid complication of CTC, especially in symptomatic
      patients. Older age and underlying concomitant colon pathology increase the risk
      of perforation. This review describes the incidence, clinical features, and
      management of colon perforations at CTC, a study that was considered risk-free
      until recently.

PMID- 16623371
TI  - [Constantin Dimitrescu-Severeanu (1840-1930)].

PMID- 16623372
TI  - [Surgical treatment of liver metastases from colorectal cancer].
AB  - We analyze our experience over a 10-year period in the surgical treatment of
      liver metastases from colorectal cancer. Between 01.01.1995 and 08.31.2005 189
      liver resections were performed in 171 patients with liver metastases from
      colorectal cancer (16 re-resections - 2 in the same patient and a "two-stage"
      liver resection in 2 patients). In our series there were 83 patients with
      synchronous liver metastases (69 simultaneous resections, 12 delayed resections
      and 2 "two-stage" liver resection were performed) and 88 metachronous liver
      metastases. Almost all types of liver resections have been performed. The
      morbidity and mortality rates were 17.4% and 4.7%, respectively. Median survival
      was 28.5 months and actuarial survival at 1-, 3- and 5-year was 78.7%, 40.4% and
      32.7%, respectively. Between January 2002 and August 2005 hyperthermic ablation
      of colorectal cancer liver metastases has been performed in 6 patients; in other
      5 patients with multiple bilobar liver metastases liver resection was associated
      with radiofrequency ablation and one patient underwent only radiofrequency
      ablation for recurrent liver metastasis. In conclusion, although the treatment of
      colorectal cancer liver metastases is multimodal (resection, ablation,
      chemotherapy and radiation therapy), liver resection is the only potential
      curative treatment. The quality and volume of remnant liver parenchyma is the
      only limitation of liver resection. The morbidity, mortality and survival rates
      after simultaneous liver and colorectal resection are similar with those achieved
      by delayed resection. Postoperative outcome of patients with major hepatic
      resection is correlated with the surgical team experience. The long-term survival
      was increased using the new multimodal treatment schemes.

PMID- 16623373
TI  - [Rectal cancer--diagnostic and therapeutic difficulties].
AB  - This paper aim is to analyze the main diagnostic and therapeutic aspects in
      rectal cancer; for this purpose we analyzed the Craiova's Surgical II Clinic
      statistics and we report them to the present literature. There were 179 rectal
      cancers, diagnosed over 10 years period (between 1995 and 2004); 163 cases were
      operated on, in 62 cases (38.03%) the surgical intervention aim being curative;
      global resection of tumor was 84.66%. The operation was preceded by preoperative
      radiotherapy in 82 cases; all cases diagnosed in the last four years in curative
      stage of disease were treated by preoperative radiotherapy. The postoperative
      mortality was 3.68% (6 cases) and the morbidity rate (55 cases - 33.74%) is still
      important, mainly because of the associated diseases. In conclusion we emphasize
      the importance of untimely diagnosis and the obligatorily sequential treatment:
      preoperative radiotherapy curative surgical resection - postoperative adjuvant
      treatment.

PMID- 16623374
TI  - [Cervical anastomotic fistula in surgery of the esophagus].
AB  - Cervical anastomotic fistula are reported in the surgical literature in 10-30% of
      the patients, providing a much longer hospitalisation, a higher morbidity and in
      some cases even mortality. Between 1997-2003, 91 patients underwent surgical
      treatment for esophageal cancers and 14 patients for chemical burns. In the
      cancer group the rate of resection was 67,03% (61 patients). In 8 patients with
      non-resection tumours a retrosternal esophageal by-pass with stomach was carried
      out. Cervical anastomosis were performed in 68 patients, by hand sutures.
      Anastomotic fistula were noted in 9 patients (13,24%). In 6 cases temporarily
      fistula occurred, with spontaneous healing by local treatment, in 8-28 days. 2
      patients required reoperation and one patient a definitive feeding jejunostomy.
      Most common causes of fistula are technical problems, ischemic gastric or colonic
      tube, postoperative respiratory failure, with prolonged hypoxia. An anastomosis
      in the neck results in less postoperative complications than one of the lower
      level.

PMID- 16623375
TI  - [Cancer of the head of pancreas--resection vs. palliative surgery].
AB  - Pancreatic cancer remains a disease with high mortality. The unspecific symptoms
      for a long time make the diagnostic difficult. Between 1995-2004, only 85 from
      465 patients with this diagnosis, had pancreatic resection. To them, we performed
      Whipple pancreaticoduodenectomy (60), pylorus preserving pancreaticoduodenectomy
      (15), pancreatico-duodenectomy with preserving of duodenum (2),
      pancreaticoduodenectomy with associated resections (5), subtotal pancreatico
      duodenectomy (30). The reconstruction after pancreatic resection was pancreatico
      jejuno anastomosis (26) and pancreatico-gastro-anastomosis (59). Morbidity was
      about 34% and the mortality was about 9%.

PMID- 16623376
TI  - [Modifications in the abdominal wall after prostheses implant in guinea pigs.
      Experimental preliminary study].
AB  - The treatment of giant incisional hernias is often not possible without the use
      of alloplastic materials (prostheses, meshes). Some of the modern prostheses seem
      to be quite "biocompatible" from the chemical point of view, but, the manner of
      using them is associated with certain complications (infection, seroma formation,
      intestinal obstruction, digestive fistula and failure of the repair). This
      preliminary experimental study on Guinea pigs had as a purpose the evaluation of
      the prostheses incorporation in the abdominal wall, the appearance of specific
      complications and the need of the biomaterial fixation. The macroscopic and
      microscopic study used 59 Guinea pigs, utilizing polypropylene (Marlex) and
      polyester (Mersilene and Plastex) prostheses, implanted pre-peritoneal and
      intraperitoneal, with or without fixation. The lack of incorporation of the
      prostheses was observed especially with the Plastex mesh (7 cases). Intestinal
      adhesions have been the rule after intraperitoneal implant of the prostheses; we
      registered a case of intestinal obstruction and a case of digestive fistula.
      Concluding, it is recommended the utilization of quality prostheses, especially
      polypropylene (Marlex) and no longer use of the Romanian polyester mesh (Plastex)
      which has obvious "biocompatible" problems. The intraperitoneal implant of the
      prostheses is not indicated. Adequate anchoring af the biomaterials prevents the
      subsequent migration.

PMID- 16623377
TI  - [Duodenal post-bulbar ulcers. Diagnostic and therapeutic problems].
AB  - Our study upon 1235 cases of duodenal ulcers (1991 - 2001) revealed a decrease of
      its morbidity rate of 10 - 12%. However, the incidence of the post-bulbar
      duodenal ulcer (P.B.D.U.) remained constant - 9,33% (115 cases) from all duodenal
      ulcers. Its diagnostic and therapeutic difficulties, its peculiar etiology,
      pathogeny, topography and evolution are the consequence of the duodeno-bilio
      pancreatic morphologic modifications, clinic polymorphism, radiologic indirect
      signs and difficult endoscopic localisation. Definitive diagnosis was set only
      intraoperatively. There are 2 forms of P.B.D.U.: proximal (D1 fixed) - 62,60% and
      distal (D2 above duodenal papilla) - 37,40%. Associated bilio-digestive lesions
      were encountered in 30 cases (26,08%). Due to its aggressive, endocrine-type
      etiology and pathogeny, evolution to severe complications and resistance to
      modern medical therapy, the PBDU should be of first surgical intent, considering
      a radical procedure whenever possible. Gastric 2/3 resection or truncal vagotomy
      with limited gastric resection were achieved in 90,43% of cases. We preferred the
      Bilroth II type anastomosis (65,20%) excluding the ulcerous lesion. Drainage of
      the duodenal stump was employed in 26% of cases. Specific postoperative morbidity
      of 12,17%, an early re-operations rate of 6,05% and postoperative mortality of
      3,47% versus 2,05% for the duodenal ulcers, emphasize the severity of the
      P.B.D.U.

PMID- 16623378
TI  - [Update in diagnosis and treatment of esophageal atresia].
AB  - The paper present a number of 17 cases of esophageal atresia, hospitalised and
      operated in a period of 4 years (2001-2004). The authors are underlining the
      importance of the prenatal diagnosis, preoperative and postoperative care, the
      chance for primary anastomosis for type III A of the disease, complications and
      prognosis related to the type of atresia. Esophageal atresia is a success of a
      complex team where the role of the neonatologist and anesthesiologist, next to
      the surgeon, is very important.

PMID- 16623379
TI  - Emphysematous cholecystitis. Review of five cases and report of septic
      musculoskeletal complications.
AB  - A variant of acute cholecystitis is emphysematous cholecystitis. Here in we
      reviewed useful clinical data of five cases of this entity. Clinical outcomes
      were uncomplicated for three patients who were treated with open cholecystectomy.
      But on the other hand we faced two septic musculoskeletal complications in two
      patients who were treated with percutaneous trans gallbladder drainage. We
      believe that we must be aware of musculoskeletal complications, whenever a
      patient with emphysematous cholecystitis is treated with percutaneous trans
      gallbladder drainage.

PMID- 16623380
TI  - [Right hepatectomy].

PMID- 16623381
TI  - [Single-stage operation in simultaneous pulmonary and liver hydatic disease].
AB  - The most frequent association of hydatic disease lesions is hepatic and pulmonary
      localisations. It is generally admitted that surgical treatment is the only
      effectiveness treatment in hydatidosis. The classic approach is the two-stage
      surgical interventions of pulmonary and liver localisation or one-stage extensive
      thoraco-phrenic-laparotomy, exclusively reserved to right pulmonary hydatic cysts
      associated with hepatic dome localisations. The study presents single-stage
      operation by thoracotomy or mini-invasive thoracic surgery and laparotomy or
      laparoscopy, or single-stage thoracic approach, as alternative of classic
      attitude and evaluates the results in 10 patients with synchronous pulmonary and
      liver hydatic cysts. Overall observations are-encouraging.

PMID- 16623382
TI  - ["The fate" of a peri-cystic-jejunostomy in the treatment of the hydatid liver
      cysts].
AB  - The persistence of a hepato-jejunal fistula after 9 years from a peri-cystic
      jejunostomy in the treatment of hydatid liver cysts is an amazing condition. We
      discover this kind of fistula during the operation for cholelithiasis. This
      association between fistula and a "after-hydatid" choledocholithiasis is an
      opportunity to discuss some pathogenic and evolutive mechanisms about both of two
      entities.

PMID- 16623383
TI  - Telemedicine in surgery.

PMID- 16623384
TI  - [Gastrointestinal stromal tumors (GIST)--a new diagnostic and therapeutic
      paradigm].

PMID- 16623385
TI  - [S.R.S. activity. Buzau chapter. The First National Traumatology Symposium, Fall,
      2005].

PMID- 16623386
TI  - Syntrophic associations in methanogenic degradation.

PMID- 16623387
TI  - Symbiosis between non-related bacteria in phototrophic consortia.

PMID- 16623388
TI  - Prokaryotic symbionts of termite gut flagellates: phylogenetic and metabolic
      implications of a tripartite symbiosis.

PMID- 16623389
TI  - Towards an understanding of the killer trait: Caedibacter endocytobionts in
      Paramecium.

PMID- 16623390
TI  - Bacterial ectosymbionts which confer motility: Mixotricha paradoxa from the
      intestine of the Australian termite Mastotermes darwiniensis.

PMID- 16623391
TI  - Extrusive bacterial ectosymbiosis of ciliates.

PMID- 16623392
TI  - Hydrogenosomes and symbiosis.

PMID- 16623393
TI  - Molecular interactions between Rhizobium and legumes.

PMID- 16623394
TI  - Molecular mechanisms in the nitrogen-fixing Nostoc-bryophyte symbiosis.

PMID- 16623395
TI  - Symbiosis of thioautotrophic bacteria with Riftia pachyptila.

PMID- 16623396
TI  - Symbioses of methanotrophs and deep-sea mussels (Mytilidae: Bathymodiolinae).
AB  - The symbioses between invertebrates and chemosynthetic bacteria allow both host
      and symbiont to colonize and thrive in otherwise inhospitable deep-sea habitats.
      Given the global distribution of the bathymodioline symbioses, this association
      is an excellent model for evaluating co-speciation and evolution of symbioses.
      Thus far, the methanotroph and chemoautotroph endosymbionts of mussels are
      tightly clustered within two independent clades of gamma Proteobacteria,
      respectively. Further physiological and genomic studies will elucidate the
      ecological and evolutionary roles that these bacterial clades play in the
      symbiosis and chemosynthetic community. Due to the overall abundance of the
      methanotrophic symbioses at hydrothermal vents and hydrocarbon seeps, they likely
      play a significant, but as of yet unquantified, role in the biogeochemical
      cycling of methane. With this in mind, the search for methanotrophic symbioses
      should not be restricted to these known deep-sea habitats, but rather should be
      expanded to include methane-rich coastal marine and freshwater environments
      inhabited by methanotrophs and bivalves. Our current understanding of the
      bathymodioline symbioses provides a strong foundation for future explorations
      into the origin, ecology, and evolution of methanotroph symbioses, which are now
      becoming possible through a combination of classical and advanced molecular
      techniques.

PMID- 16623397
TI  - Symbioses between bacteria and gutless marine oligochaetes.

PMID- 16623398
TI  - Roles of bacterial regulators in the symbiosis between Vibrio fischeri and
      Euprymna scolopes.

PMID- 16623399
TI  - Molecular requirements for the colonization of Hirudo medicinalis by Aeromonas
      veronii.

PMID- 16623400
TI  - Low flow and closed-circuit anesthesia--they deserve to be more widely used both
      from the financial and physiology viewpoints.

PMID- 16623401
TI  - Comparing the effects of minimal low-flow desflurane with that of semi-close high
      flow desflurane on perioperative cytokine response in patients undergoing
      gastrectomy.
AB  - BACKGROUND: Anesthetic techniques may influence the perioperative cytokine
      response. We investigate two anesthetic techniques: minimal low-flow anesthesia
      (LFA) and semi-closed high flow anesthesia (HFA) with desflurane on the effect of
      cytokine response in gastrectomy. METHODS: Forty patients scheduled to undergo
      elective gastrectomy were randomly allocated to LFA (0.3 mL/min) or HFA (2 L/min)
      group. Blood was sampled for measurement of tumor necrosis factor (TNF),
      interleukin (IL)-6, IL-8, and IL-1 receptor antagonist (RA) at scheduled
      intervals. Hemodynamic responses, desflurane concentrations, numbers of patient
      using cardiovascular agents, and frequency of vaporizer manipulations were
      recorded during the operation. RESULTS: For patients in the LFA group, production
      of IL-8 was significantly less increased at the end of the surgical procedure;
      however there was no significant difference in total production between groups.
      There was no significant difference in TNF, IL-6, and IL-1RA production
      throughout the observed period. The desflurane vaporizer was adjusted more
      frequently (4 [13-6] versus 2 [1-3] times) for patients in the HFA group, and
      more patients in this group required the use of cardiovascular agents (10 versus
      4) than patients in the LFA group during the operation. CONCLUSIONS: The current
      study demonstrates that smaller increase in cytokine production in the LFA than
      HFA with desflurane for the patients receiving gastrectomy.

PMID- 16623402
TI  - Evaluation of the longitudinal contraction of the ventricle septum in patients
      undergoing off-pump coronary artery bypass graft surgery by strain rate imaging.
AB  - BACKGROUND: Strain rate (SR) imaging is an emerging technique for assessing
      myocardial systolic and diastolic functions. This technique can provide
      assessment in real time and color mapping; it also can detect ischemia at its
      earlier stages in comparison with visual estimation of wall motion with other
      techniques. METHODS: This study group consisted of 9 patients undergoing elective
      coronary artery bypass graft (CABG) surgery. After general anesthesia with
      sevoflurane (end-tidal 1.8%) in air/oxygen mixture, a complete transesophageal
      echocardiography (TEE) study was performed with an ultrasound machine. Myocardial
      wall strain rate imaging was then preformed off-line using a customized computer
      software (Echopac, Windows 2000 version 2.1, General Electric) running on a
      Compaq P4 computer. The experimental protocol was divided into 6 parts: (1) T1:
      30 minutes after general anesthesia completed, (2) T2: after opening the sternum
      and pericardium, (3) T3: left anterior descending coronary artery(LAD) snared for
      the preparation of ischemic pre-conditioning (SLAD), (4) T4: after anastomosing
      left internal mammary artery (LIMA) on LAD, (5) T5: before closing the sternum
      and pericardium and (6) T6: after closing the sternum and pericardium. RESULTS:
      From strain rate imaging, peak systolic SRs were reduced or inverted over LAD
      perfused area during the SLAD period. In apical segments, peak systolic SR
      changed from -0.45 +/- 0.48 to 0.42 +/- 0.63 (P < 0.05), whereas peak diastolic
      SR changed from 0.34 +/- 0.61 to -0.80 +/- 1.08 (P < 0.05). In the middle septum,
      peak systolic SR changed from -0.67 +/- 0.51 to -0.43 +/- 0.50 (P < 0.05), while
      peak diastolic SR changed from 0.47 +/- 0.44 to -0.64 +/- 0.84 (P < 0.05). After
      LIMA grafting, peak systolic SR changed from 0.42 +/- 0.63 to -0.61 +/- 0.40 (P <
      0.05), as against peak diastolic SR which changed from -0.80 +/- 1.08 to 0.21 +/-
      0.44 (P < 0.05) in the apical septum. Peak systolic SR changed from -0.43 +/-
      0.50 to -0.75 +/- 0.46 (P < 0.05), whereas peak diastolic SR changed from -0.64
      +/- 0.84 to 0.64 +/- 0.88 (P < 0.05) in the middle septum. CONCLUSIONS:
      Postsystolic shortening is a marker for both ischemia and successful myocardial
      reperfusion. By strain rate imaging, we could detect ischemia with a more
      sensitive and specific method. For anesthesiologists and surgeons, it can be an
      intraoperative tool for assessing ventricular function after reperfusion.

PMID- 16623403
TI  - The direct cardiac effect of propofol on intact isolated rabbit heart.
AB  - BACKGROUND: The objective of the current study was to determine the direct effect
      of propofol on intact isolated rabbit heart using the modified Langendorff model.
      METHODS: Eighteen rabbits were decerebrated under light ether anesthesia. Their
      hearts were then excised and prepared pursuant to the modified Langendorff model.
      Left ventricular pressure, left ventricular contractility (dp/dt) and heart rate
      were recorded in the absence of propofol and in the presence of propofol of four
      different concentrations (1, 5, 25, 50 mg/L). In one group of hearts (N=11) the
      heart rate was not paced. In another group of hearts (N=7), the hearts were paced
      (during the control period and in propofol of each concentration) at a rate
      slightly higher than control rate and then allowed to revert to original state;
      pressure and contractility were measured and taken at both paced and unpaced
      rates. RESULTS: In the unpaced group of hearts, a significant dose-dependent,
      negative effect on both left ventricular pressure and contractility was found at
      the two higher propofol concentrations (25 and 50 mg/L). A significant heart rate
      decrease was also revealed at these two concentrations. In the paced group, the
      left ventricular pressure and dp/dt also decreased significantly at higher
      propofol concentrations, and they did not return toward control values even
      though the heart was paced at the baseline unpaced rate. CONCLUSIONS: Propofol
      depressed left ventricular pressure and contractility and heart rate in a dose
      dependent manner at higher concentrations. These negative cardiac effects were
      independent of changes in heart rate.

PMID- 16623405
TI  - Difficult oral endotracheal intubation in an acromegalic patient receiving
      transsphenoidal surgery--a case report.
AB  - Patients suffering from acromegaly are associated with increased risks of
      difficult airway management. We report a case of acromegaly scheduled for
      transsphenoidal resection of pituitary adenoma under general anesthesia in whom
      all possible means failed us in the insertion of the endotracheal tube (ET)
      through the mouth, a procedure essential for transsphenoidal surgery. The
      operation was called off and for securing his compromised airway a nasal ET was
      placed under fiberoptic bronchoscopy. Five days later, awake oral fiberoptic
      intubation was successful under topical anesthesia. We suggest that oral
      endotracheal intubation performed awake under topical anesthesia with the aid of
      a fiberoptic bronchoscope is a choice approach in acromegalic patients with
      predicated difficult airway who are to receive surgery.

PMID- 16623404
TI  - Closed-circuit anesthesia preserves skin blood flow during surgery.
AB  - BACKGROUND: Closed-circuit anesthesia (CCA) has been suggested to provide better
      hemodynamic stability, but the relative contribution of CCA to the control of
      blood flow in microcirculation is not defined. It is hypothesized that isoflurane
      based CCA provides a favorable skin blood flow mediating via lesser circulatory
      response to surgical stimulation. This study was purposed to compare the effects
      of isoflurane conveyed by CCA with that by semiclosed anesthesia (SCA) on the
      preservation of skin blood flow in the forearm. METHODS: Twenty seven patients
      scheduled for colorectal surgery were enrolled for the study and randomly
      assigned to one of two groups, either receiving CCA (n=14) or SCA (n=13).
      Anesthesia was induced with fentanyl (100 ig) and thiopental (4-5 mg/kg), and
      intubation was facilitated with pancuronium priming (0.015 mg/kg) and
      succinylcholine (1.25 mg/kg). Two percent isoflurane in high O2 flow (3 L/min)
      was given for 10 min to each patient initially to wash isoflurane in the
      functional residual capacity of both lungs and the breathing circuit. In the CCA
      group, after insoflurane wash-in the 02 flow was reduced less than 250 mL/min
      with isoflurane vaporizer setting adjusted to 3-5% to keep inspired isoflurane at
      2% for maintenance of anesthesia. In patients of in the SCA group, anesthesia was
      maintained with isoflurane in 3 L/min O2 flow keeping the inspired isoflurane
      concentration at 2% throughout the surgery. A laser Doppler flowmetry (Moore
      instrument, Axminster, England) was used to measure skin blood flow (SBF) at the
      thenar eminence of left hand. Skin blood flow was determined and was taken as
      baseline (100%) at the 10th min after tracheal intubation. Thereafter, the
      magnitude of SBF was determined likewise every 30 minutes over the two-hour
      study. The hemodynamic and respiratory parameters were measured at every 5
      minutes in both groups. RESULTS: In comparison with the SCA group, the CCA group
      had a greater magnitude of skin blood flow (106 +/- 13% vs. 75 +/- 17%; 104 +/-
      14% vs. 68 +/- 14% P < 0.01) at the 60th and 120th min. Also, patients who
      received SCA had higher mean arterial pressure (MABP) (82 +/- 8 vs. 78 +/- 8; 89
      +/- 6 vs. 77 +/- 10, P < 0.05) and heart rate (HR) (80 +/- 9 vs. 73 +/- 9; 82 +/-
      15 vs. 71 +/- 14, P < 0.05) at the 60th and 120th min. CONCLUSIONS: Closed
      circuit technique for isoflurane anesthesia is feasible and advantageous. It not
      only facilitates favorable skin blood flow but also provides better hemodynamic
      stability in comparison with semiclosed technique for isoflurane anesthesia.

PMID- 16623406
TI  - Cardioversion corrects cardiac arrhythmia and reverts the resultant reversed
      shunt flow direction during transcatheter closure of atrial septal defect--a case
      report.
AB  - Closure of atrial septal defect (ASD) is critically dependent on the shunt flow
      direction. However, shunt flow direction through ASD may change under variable
      clinical conditions. We present here a 53-year-old woman with a confirmed left-to
      right shunt ASD prior to Amplatzer Septal Occluder placement. The development of
      atrial flutter during the procedure had been found to change the shunt from
      unidirectional to bidirectional and the procedure was then forced to a temporary
      halt. The cardiac arrhythmia and altered shunt direction simultaneously reverted
      to the old state after cardioversion. A successful placement of Amplatzer septal
      occluder was successfully performed afterward and she recovered uneventfully.

PMID- 16623407
TI  - Severe bronchospasm during laryngeal mask airway placement in an infant.
AB  - A 35-day-old male infant was scheduled for bilateral inguinal herniorrhaphy. No
      history of recent upper airway infection or other reactive respiratory disease
      was noted before anesthesia. Breath holding was noted immediately after laryngeal
      mask airway (LMA) insertion. Removal of the LMA and positive pressure ventilation
      via face mask did not solve the problem. On suspicion of laryngospasm, tracheal
      intubation facilitated by muscule relaxant was performed. However, when the
      patient was ventilated, high airway pressure, absence of chest wall movement and
      elevated end-tidal CO2 were noted. Despite visual confirmation of correct
      placement of tracheal tube, oxygen desaturation and bradycardia developed
      rapidly. After deepening the inhalational anesthesia of sevoflurane and
      concomitant administration of intravenous lidocaine, the patient's respiratory
      condition turned for the better and became compliable. Respiratory dysfunction
      may be caused by severe bronchospasm induced by placement of the LMA. The
      pathophysiology and risk factors of bronchospasm related to the LMA placement are
      discussed in the text.

PMID- 16623408
TI  - Macroglossia after posterior fossa surgery in the prone position--a case report.
AB  - We report a case of prominent postoperative macroglossia after posterior fossa
      surgery in the prone position. The potential risk factors predisposing to its
      generation, prophylactic measures to avoid it and treatments for its alleviation
      are reviewed and discussed.

PMID- 16623409
TI  - Time course of spontaneous recovery of subacute fat embolism syndrome--a case
      report.
AB  - Pulmonary embolism is not uncommonly encountered in orthopedic patients with high
      risks, such as prolonged immobility, obesity, past or family history of
      thromboembolism, pelvic and long bone fractures. Here we report a young male
      patient with a residual cerebral arteriovenous malformation post-craniotomy
      suffered from acute severe hypoxemia after sustaining a simple fracture of the
      left femur shaft from a motorcycle accident. The emergent surgery was deferred in
      view of suspectable pulmonary embolism. Under supportive treatment, the condition
      spontaneously resolved, and the surgery was later performed uneventfully. To the
      best of our knowledge, this was the first instance that a pulmonary embolism
      (suspected subacute fat embolism syndrome) which ran in a natural course to
      spontaneous resolution was observed. We would like to report our clinical
      observation, and discuss the principle of anesthetic management in the text.

PMID- 16623410
TI  - Two different anesthetic managements of a patient with von Gierke's disease.
AB  - Von Gierke's disease, a form of glycogen storage disturbance, is a rare metabolic
      disorder with important implications for anesthesiologists. It is caused by the
      lack of the glucose-6-phosphatase, which is necessary for the liver to convert
      glycogen to glucose. To avoid severe hypoglycemia, it is crucial to keep oral
      feeding at intervals 2-3 hr for maintaining a normal blood sugar level. The
      metabolic derangements of von Gierke's disease may result in serious
      complications in patients undergoing surgery and anesthesia. We report the
      anesthetic managements of a patient with von Gierke's disease in two operations
      with different encounters.

PMID- 16623412
TI  - Is peritoneal dialysis different in Japan?

PMID- 16623411
TI  - Cardiac arrest during spinal anesthesia: a report of two cases.
AB  - Spinal anesthesia is a widely practiced technique for both elective and emergency
      procedures. It is so recommended because of its efficacy and safety. Cardiac
      arrest during spinal anesthesia is considered as a "very rare", "unusual", and
      "unexpected" event. We report here two instances of cardiac arrest during spinal
      anesthesia in young healthy people. Discussions on the causes, management, and
      prevention of cardiac arrest following spinal anesthesia are also brought forward
      in the text.

PMID- 16623413
TI  - Status of peritoneal dialysis in Japan.

PMID- 16623414
TI  - Is technique survival on peritoneal dialysis better in Japan?
AB  - Technique failure resulting in transfer to hemodialysis (HD) remains one of the
      most important challenges in Longterm peritoneal dialysis (PD). In general, the
      proportion of patients transferring from PD to HD is much greater than the
      proportion transferring from HD to PD. However, technique failure rates differ
      considerably between and within countries. The question arises as to how
      technique failure rates in Japan compare with those in other countries. To
      address this issue, we reviewed the literature and our experience of 139 incident
      continuous ambulatory peritoneal dialysis (CAPD) patients from January 1995 to
      December 1999. Based on our review, we estimate that the 5-year technique
      survival rate in Japanese CAPD patients is approximately 70%, and that technique
      failure rate is around 7% per year. This rate is significantly lower than that in
      many other countries. The most common reasons for technique failure in Japan are
      peritoneal membrane failure, ultrafiltration loss, and inadequate dialysis.
      Another factor contributing to the low technique failure rate in Japan is an
      extremely low peritonitis rate. This may be related to good sanitation and
      excellent PD training programs. Peritoneal membrane failure continues to be the
      major challenge for long-term technique survival on PD in Japan.

PMID- 16623415
TI  - Fluid status and its management in Japanese peritoneal dialysis patients.
AB  - This article reviews published studies related to fluid status of Japanese
      peritoneal dialysis (PD) patients and its impact on technique and patient
      survival. In addition, some specifics related to clinical background that
      potentially influence fluid status are described. According to a multicenter
      survey conducted in Japan, nearly 25% of Japanese PD patients are overhydrated.
      Available data indicate that a high salt diet may conceivably play an important
      role in the pathogenesis of fluid overload in Japanese PD patients, and it in
      turn negatively impacts patient prognosis. Because of the generally adopted
      policy among Japanese PD experts to avoid regular use of 3.86% glucose solution,
      icodextrin solution is now used in more than one third of all patients. Other
      means of managing fluid overload, such as drug therapy, combination
      (complementary) therapy with hemodialysis, and low sodium PD solution, are also
      explored and summarized in this article.

PMID- 16623416
TI  - Combination therapy with peritoneal dialysis and hemodialysis.

PMID- 16623417
TI  - The Japanese health-care system and reimbursement for dialysis.
AB  - Like most countries, Japan is facing constraints on expansion of health system
      financial resources. There are almost 250000 Japanese patients with end-stage
      renal disease and almost all are managed by chronic dialysis. Hospital
      hemodialysis is the modality used by 96% of these patients. The Japanese health
      care system has tended to support resource-intensive treatments because the fee
      for-service remuneration system has rewarded their utilization. This has
      benefited hemodialysis at the expense of peritoneal dialysis. However, this may
      now be changing. Case management and global budget-related approaches are being
      more widely introduced, as are incentives to reward more efficient treatment
      options. The relative costs of dialysis modalities are difficult to appreciate,
      as center-based services, such as hospital hemodialysis, are dependent upon fixed
      resources, while home-based options, such as peritoneal dialysis, are dependent
      upon variable resources. The aim of this review is to reconcile various sources
      of information relevant to end-stage renal disease funding in Japan. The review
      will suggest that modifying the approach to modality selection could lead to more
      efficient allocation of future dialysis-related resources and so reduce the
      strain on Japan's health-care budget.

PMID- 16623418
TI  - Peritoneal mesothelial cell culture and biology.
AB  - The peritoneal mesothelium is composed of an extensive monolayer of mesothelial
      cells that lines the body's serous cavity and internal organs and was previously
      thought to act principally as a protective nonadhesive lubricating surface to
      facilitate intracoelomic movement. With the introduction of peritoneal dialysis
      over three decades ago, there has been much interest in the cell biology of
      peritoneal mesothelial cells. Independent studies have highlighted specific
      properties of the peritoneal mesothelial cell, including antigen presentation,
      regenerative properties, clearance of fibrin; synthesis of cytokines, growth
      factors, and matrix proteins; and secretion of lubricants to protect the tissue
      from abrasion, adhesion, infection, and tumor dissemination. It is now evident
      that the mesothelium is not merely a passive membrane but, rather, a dynamic
      membrane that contributes substantially to the structural, functional, and
      homeostatic properties of the peritoneum. Since peritoneal mesothelial cells in
      culture possess immunohistochemical markers identical to mesothelial stem cells,
      the culture of mesothelial cells offers researchers an essential tool to assess
      their morphologic, structural, and functional properties. This review will
      discuss current procedures to isolate peritoneal mesothelial cells from human
      omental specimens, animal sources, and spent dialysate. Furthermore, the
      functional and morphologic properties of mesothelial cells are discussed,
      together with the potential use of mesothelial cell culture in research and
      clinical applications.

PMID- 16623419
TI  - Escherichia coli peritonitis in patients undergoing peritoneal dialysis: a
      serious problem that may get worse.

PMID- 16623420
TI  - Hernia repair without delay in initiating or continuing peritoneal dialysis.

PMID- 16623421
TI  - Clinical experience with tamoxifen in encapsulating peritoneal sclerosis.

PMID- 16623422
TI  - Advanced glycation and advanced oxidation protein products: the effect of
      peritoneal dialysis.

PMID- 16623423
TI  - Mystery in the dark: can antibiotic prophylaxis enlighten us?

PMID- 16623424
TI  - Risk factors and outcomes of extended-spectrum beta-lactamase-producing E. coli
      peritonitis in CAPD patients.
AB  - OBJECTIVE: To determine the risk factors and outcomes of peritonitis caused by
      extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in continuous
      ambulatory peritoneal dialysis (CAPD). PATIENTS AND METHODS: Episodes of E. coli
      CAPD peritonitis in our unit from October 1994 to August 2003 were reviewed.
      Demographic data, underlying medical conditions, recent use of gastric acid
      inhibitors (including H2 antagonist and proton pump inhibitor), recent antibiotic
      therapy, antibiotic regimen for peritonitis episodes, sensitivity test results of
      the E. coli isolated, and clinical outcomes were examined. RESULTS: Over a 10
      year study period, 88 episodes of E. coli peritonitis were recorded; 11 of the 88
      cases were caused by ESBL-producing E. coli. Recent use of cephalosporins and
      gastric acid inhibitor were associated with the development of ESBL-producing E.
      coil peritonitis. Compared with non-ESBL-producing E. coli peritonitis, more
      cases in the ESBL-producing E. coli group developed treatment failure (45.5% vs
      13.0%, p = 0.02) and died of sepsis (27.3% vs 3.9%, p = 0.02). Peritoneal failure
      rate was higher in the ESBL-producing E. coli group, although the difference was
      not statistically significant (18.2% vs 3.9%, p = 0.12). CONCLUSION: Peritonitis
      caused by ESBL-producing E. coli is associated with worse clinical outcomes. The
      use of cephalosporins and gastric acid inhibitors may contribute to its
      development. Further studies are warranted to investigate and determine the
      predisposing factors for ESBL-producing E. coli peritonitis.

PMID- 16623425
TI  - Prevalence and management of hernias in peritoneal dialysis patients.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of hernias before
      and after the start of continuous ambulatory peritoneal dialysis (CAPD) in
      patients with end-stage renal disease, and to evaluate the result of a proposed
      surgical treatment. DESIGN: Prospective observational study. SETTING: University
      hospital. PATIENTS: 122 patients who started CAPD from 1994 to 2000; 26 hernias
      were diagnosed in 21 (17.2%) patients. MAIN OUTCOME MEASURES: Finding of hernias;
      morbidity associated with catheter insertion and hernia repair; recurrence of
      hernias. RESULTS: 19 hernias were detected in 15 patients (12.3%) before they
      began CAPD; only 7 hernias were observed while on CAPD. Umbilical (61.5%) and
      inguinal (26.9%) hernias were the most common. Multiple hernias were detected in
      4 patients. Simultaneous repair of hernia and catheter insertion was performed in
      patients with pre-existing hernias. Under local anesthesia, most patients were
      operated on with surgical techniques of tension-free hernioplasty using a
      polypropylene mesh. Only mild post-operative complications were recorded: 3
      seromas and 1 hematoma. No fluid leakage was found in our series. There were no
      long-term complications (infection or recurrence) related to the mesh.
      CONCLUSIONS: 73% of hernias in peritoneal dialysis patients occur before starting
      dialysis. Hernia problems in these high-risk patients can be safely solved using
      a careful technique with application of tension-free hernioplasty. Most may be
      repaired under local anesthesia with simultaneous catheter insertion.

PMID- 16623426
TI  - Four consecutive cases of peritoneal dialysis-related encapsulating peritoneal
      sclerosis treated successfully with tamoxifen.
AB  - Sclerosing peritonitis is a rare complication of peritoneal dialysis (PD). In
      encapsulating peritoneal sclerosis (EPS), the most severe form of the disease,
      the intestine is entrapped in a fibrous tissue, causing intestinal obstruction.
      Patients are typically seriously ill, with evidence of infection and requirement
      for parenteral nutrition. A mortality rate of 73% has been reported. There is no
      established medical treatment and surgery has offered variable results. Our unit
      provides renal replacement therapy for a population of about 2 million. The
      prevalent population of PD patients averages 110. The cumulative PD population
      since January 1993 is 643, with an EPS prevalence of 0.6%. Influenced by the
      first case reported by Allaria in 1999 suggesting benefit of tamoxifen in
      treating EPS, we have treated with tamoxifen the four consecutive cases of EPS
      that have presented since 1999. All 4 patients have survived and recovered
      intestinal function. ALL showed prior evidence of peritoneal dysfunction with
      ultrafiltration failure and were characterized by long duration of PD therapy
      rather than multiple episodes of peritonitis. We conclude that tamoxifen is a
      highly promising therapy in EPS, hitherto a usually fatal condition. This
      description of its efficacy in acutely ill patients with EPS complements its
      possible prophylactic use in patients with the earlier and milder disease,
      sclerosing peritonitis. A high index of clinical suspicion for sclerosing
      peritonitis is desirable, perhaps facilitated by routine screening of at-risk
      patients.

PMID- 16623427
TI  - Changes in glycation and oxidation markers in patients starting peritoneal
      dialysis: a pilot study.
AB  - BACKGROUND: The high incidence of cardiovascular disease in uremic patients makes
      it a major cause of morbidity and mortality in those patients. Uremia is
      associated with carbonyl and oxidative stress, which result in the enhanced
      formation of glycation and oxidation products respectively. In the present study,
      the blood levels of advanced glycation end products (AGEs) and advanced oxidation
      protein products (AOPPs) were investigated in uremic patients prior to and after
      initiation of peritoneal dialysis (PD). METHODS: 22 patients [11 nondiabetic (G1)
      and 11 diabetic (G2) subjects] were enrolled in a single-center prospective
      study. Prior to starting PD (TO) and 6 and 12 months later, changes in AGE and
      AOPP levels were analyzed in the total study population and in each group
      (Friedman test, intragroup). At each time point, a comparison was made between
      the levels of the above-mentioned products in G1 and G2 (Mann-Whitney test,
      intergroup). Correlations between AGE or AOPP levels and residual renal function,
      peritoneal creatinine clearance, glucose peritoneal equilibration test, or daily
      dextrose exposure were analyzed using the Pearson test. RESULTS: At TO, no
      significant difference was found between the two groups for AGE or AOPP levels.
      Initiation of PD was followed by an increase in AGE levels in all patients (p <
      0.01 at 6 and 12 months). AGE Levels were higher in G2 than in G1 at 12 months
      after the start of PD (p < 0.05). In contrast to G2 results, initiation of PD in
      G1 led to reduced AOPP Levels (at 6 and 12 months, p = 0.01 and p < 0.05
      respectively). However, no correlation between AGE or AOPP levels and residual
      renal function, peritoneal creatinine clearance, glucose peritoneal equilibration
      test, or daily dextrose exposure could be established. CONCLUSION: This study
      demonstrates that PD is associated with an increase in levels of blood glycation
      end products, particularly in diabetic patients, but also with a decrease in
      oxidative products such as AOPPs, especially in nondiabetic subjects.

PMID- 16623428
TI  - Continuous ambulatory peritoneal dialysis in patients with hepatitis B liver
      disease.
AB  - OBJECTIVE: We hypothesized that patients with hepatitis B virus infection and
      cirrhosis are more susceptible to peritonitis as a complication of peritoneal
      dialysis (PD). METHODS: A retrospective study was carried out to compare
      peritonitis rates between cirrhotic and non-cirrhotic patients with hepatitis B
      virus infection. RESULTS: Between 1994 and 2004, 25 PD patients with hepatitis B
      cirrhosis and 36 patients with hepatitis B without cirrhosis were included for
      analysis. Mean follow-up duration was 52 months. Subjects with hepatitis B
      cirrhosis consisted of more males and had higher total body weight. No cirrhotic
      patients (20 of them being Child-Pugh class A, 2 class B, and 3 class C) had
      undergone portosystemic shunting or liver transplantation. Cirrhotic patients had
      slightly higher bilirubin concentration than the non-cirrhotic group (22 +/- 50
      vs 9 +/- 4 micromol/L, p = 0.16). There was no difference in median peritonitis
      free survival between cirrhotic and non-cirrhotic patients (40 vs 37 months, p =
      0.64 by log-rank test). The average peritonitis rate was 1 episode every 19.2
      patient-months in the cirrhotic group and 1 episode every 20.5 patient-months in
      the non-cirrhotic group. Time to first peritonitis did not differ between the two
      groups with respect to gram-negative organisms (p = 0.88) or gram-positive
      organisms (p = 0.52). Cirrhotic patients had more frequent Streptococcus species
      peritonitis, which accounted for 13% of all peritonitis episodes, as opposed to
      2% among the non-cirrhotic patients (p = 0.01). Overall treatment response rate
      and outcome did not differ between patients with and patients without cirrhosis.
      CONCLUSIONS: Peritonitis-free survival of cirrhosis patients infected by
      hepatitis B virus compares favorably with thatin patients without cirrhosis. The
      presence of liver cirrhosis does not appear to compromise PD outcome.

PMID- 16623429
TI  - Changes in total sodium intake do not lead to proportionate changes in total
      sodium removal in CAPD patients.
AB  - BACKGROUND: Dietary salt and fluid restriction is important in controlling fluid
      balance in patients on continuous ambulatory peritoneal dialysis (CAPD). However,
      it is often difficult to monitor patients' dietary total sodium intake (TSI).
      Usually, total sodium removal (TSR), the sum of urinary sodium removal (USR) and
      dialysate sodium removal (DSR), is suggested to represent TSI. In the present
      study, we investigated the reliability of using TSR as a surrogate to TSI in CAPD
      patients. METHODS: 40 clinically stable CAPD patients were closely followed for 3
      months. Their TSI, USR, DSR, and fluid status were measured twice: at baseline
      and at the end of this study respectively. Fluid status was evaluated by
      bioimpedance analysis. Patients with increased sodium intake (group ISI) or
      decreased sodium intake (group DSI) (both >0.5 g/day or >21.74 mmol/day elemental
      sodium) were included in this study. RESULTS: There were 15 patients in group ISI
      and 9 patients in group DSI. During the follow-up, although TSI increased in
      group ISI and decreased in group DSI (p < 0.05), there were no significant
      changes in USR, DSR, or TSR in either group. No relationship was found between
      TSI and TSR. Changes in weight, blood pressure, urine volume, ultra-filtration,
      and small solute removal (Kt/V and creatinine clearance) were not statistically
      significant between the two groups. Fluid status deteriorated in group ISI and
      improved in group DSI (p < 0.05). CONCLUSIONS: Our study suggests that changes in
      total sodium intake do not lead to proportionate changes in total sodium removal
      in CAPD patients. Therefore, TSR (the sum of USR and DSR) should be used
      cautiously to monitor TSI in this patient population.

PMID- 16623431
TI  - Impact of first dialysis modality on outcome of patients contraindicated for
      kidney transplant.
AB  - BACKGROUND: We compared, in patients contraindicated for kidney transplant,
      outcomes between those patients who were only on hemodialysis (HD) and those who
      were given peritoneal dialysis (PD) as first renal replacement therapy (RRT).
      DESIGN: Prospective, population-based cohort study of incident cases of end-stage
      renal disease between June 1997 and June 1999. SETTING: A network of dialysis
      care: NEPHROLOR, that is, all the renal units in Lorraine, one of the 22 French
      administrative regions (population over 2.3 million people). PARTICIPANTS: 387
      patients were contraindicated for kidney transplant during the first 2 years of
      RRT: 284 were on HD, 103 on PD. Mean age was 67.6 +/- 11.3 years for HD patients
      and 70.8 +/- 11.4 years for PD patients (p = 0.015). MAIN OUTCOME MEASURES:
      Mortality until June 2003, hospitalization over the 2 first years of RRT, and
      Kidney Disease and Quality of Life Short Form (KDQOL-SF) 6 and 12 months after
      initiation of RRT. RESULTS: HD patients were more likely to die from cardiac or
      cerebrovascular causes, PD from cachexia or withdrawal from dialysis. Whatever
      mode of RRT, the unadjusted 2-year and 5-year survival rates were similar (p =
      0.98). The rate of total duration of hospital stay per month of RRT was similarin
      HD and PD groups: 2.7 +/- 4.5 and 2.9 +/- 4.2 days respectively (p = 0.7). PD was
      associated with better quality of life than HD. The dimensions Role limitation
      due to emotional function, Burden of kidney disease, and Role limitation due to
      physical function ranked first, second, and third for PD. CONCLUSION: In
      Lorraine, end-stage renal disease patients who were given PD as first-line RRT
      had no excess of death risk or hospitalizations, and better quality of life the
      first year of RRT.

PMID- 16623430
TI  - Fluorodeoxyglucose positron emission tomography detects the inflammatory phase of
      sclerosing peritonitis.
AB  - OBJECTIVE: We studied the effectiveness of 18F-fluorodeoxyglucose positron
      emission tomography (FDG-PET) in detecting inflammation in known or suspected
      cases of sclerosing peritonitis in patients on peritoneal dialysis (PD). DESIGN:
      We undertook FDG-PET scanning in PD patients presenting with symptoms or signs
      suggestive of sclerosing peritonitis (SP), and in patients on long-term PD with
      no symptoms of SP. SETTING: The study was performed in a PD unit in a tertiary
      care hospital. PATIENTS AND METHODS: Three patients with known or strongly
      suspected SP underwent FDG-PET scans, 1 within 3 months of presentation with
      symptoms and 2 who were scanned more than 9 months after presentation. One
      patient was scanned at an early and a late time point. Five patients who had been
      on PD for more than 5 years and who were asymptomatic also underwent FDG-PET
      scanning. Scans were interpreted by a specialist in nuclear medicine. RESULTS:
      The scan performed in the early stages of SP showed increased peritoneal uptake.
      However, three scans taken more than 9 months after presentation with suspected
      SP showed mild peritoneal abnormalities only. One of 5 asymptomatic long-term PD
      patients showed increased peritoneal uptake associated with loss of
      ultrafiltration and high transporter status. CONCLUSIONS: FDG-PET scanning may be
      a useful adjunct in the diagnosis of the acute phase of SP. More study is needed
      to define its role in the diagnosis of SP in asymptomatic PD patients.

PMID- 16623432
TI  - Procalcitonin and conventional markers of inflammation in peritoneal dialysis
      patients and peritonitis.
AB  - OBJECTIVES: To determine the significance of a newly described marker of
      inflammation procalcitonin (PCT), and to investigate its relationship to
      conventional markers of inflammation, such as C-reactive protein (CRP),
      fibrinogen, and erythrocyte sedimentation rate (ESR), in patients on peritoneal
      dialysis (PD) and with peritonitis. DESIGN: A prospective, observational clinical
      study. SETTING: The Nephrology Division of a University-affiliated teaching
      hospital. PATIENTS AND METHODS: 51 consecutive patients on PD were included in
      the study. Of this number, 16 developed peritonitis during the observational
      period. Baseline PCT, CRP, and fibrinogen concentrations and ESR of 51 PD
      patients were determined at a time point (TB) prior to any evidence of infection.
      These results were compared with laboratory values from 74 hemodialysis patients
      and 34 nonuremic control subjects. All PD patients then were followed
      prospectively for evidence of peritonitis. In addition to routine blood tests,
      including hemoglobin and leukocyte count, and routine biochemical tests, blood
      samples were taken to measure PCT, CRP, and fibrinogen concentrations and ESR at
      the time (T0) when patients first were diagnosed with PD peritonitis and also on
      the 4th (T4) and the 14th (T14) days after treatment for peritonitis was
      initiated. PCT was assayed by immunoluminometry. RESULTS: No significant
      difference was observed between baseline median serum PCT concentrations in PD
      and hemodialysis patients; however, in both groups, baseline median PCT
      concentrations were significantly higher than those of nonuremic controls (p <
      0.05). The 16 patients on PD who developed peritonitis had 21 PD peritonitis
      episodes during the study period. The increased PCT concentration observed at T0
      in PD peritonitis episodes decreased with therapy, and this change was
      statistically significant (p < 0.05). In a receiver operating characteristic
      curve analysis for peritonitis, the area under the curve (AUC) for PCT was 0.80,
      which was significantly lower than the AUC for CRP and greater than the AUCs for
      fibrinogen and ESR. The sensitivity of PCT for peritonitis was lower than the
      sensitivity of conventional markers of inflammation; however, the specificity of
      PCT was higher. CONCLUSIONS: Median serum PCT concentration in PD patients was
      significantly higher than in nonuremic controls but not hemodialysis patients.
      Serum PCT concentrations may serve as a useful adjunct to traditional markers of
      inflammation in detecting and monitoring inflammation and peritonitis in PD
      patients.

PMID- 16623433
TI  - Antibiotic prophylaxis in an animal model of chronic peritoneal exposure.
AB  - OBJECTIVES: Acute infection in an animal model of chronic peritoneal dialysis
      (PD) induces structural changes in the peritoneum and altersfunctional
      characteristics of transport. These changes may compromise observations of the
      chronic effects of dialysis solutions. To test the hypothesis that antibiotics
      would prevent acute infection without affecting transport and structural
      properties, we characterized the frequency of infection in our rat model of PD
      and examined whether the inclusion of antibiotics in the dialysis solution
      altered the transport and structural properties of the peritoneum. DESIGN: Female
      Sprague-Dawley rats were aseptically injected daily under gas anesthesia with 30 
      40 mL of a sterile solution for 2 months via a peritoneal catheter tunneled to a
      subcutaneous port. Solutions used were Krebs-Ringer bicarbonate (KRB) alone, KRB
      with antibiotics (cefazolin 200 mg/L and gentamicin 2 mg/L), KRB with 4% glucose,
      and KRB with both glucose and antibiotics. After 2 months, osmotic filtration
      andsolute transport were assessed in each animal and peritoneal fluid was
      collected for bacterial culture. Angiogenesis was evaluated by quantitative image
      analysis of tissue sections stained with CD31. Tissue content of collagen,
      hyaluronic acid, and sulfated glycosaminoglycan was determined. RESULTS:
      Technique survival (successful PD for 2 months) and infection rate were
      comparable among all treated groups. There were no differences between the groups
      in transport properties. Structural changes were comparable between groups, with
      or without antibiotics. CONCLUSIONS: Addition of antibiotics to the dialysis
      solution did not affect thetransport characteristics of the peritoneum or the
      pathologic reaction of the tissue to the PD solution.

PMID- 16623434
TI  - The role of the glyoxalase pathway in reducing mesothelial toxicity of glucose
      degradation products.
AB  - BACKGROUND: The glucose degradation products (GDP) presentin conventional
      peritoneal dialysis fluids (PDF) may exert adverse effects toward human
      peritoneal mesothelial cells (HPMC). Some GDP can be detoxified by the
      glyoxalase/ glutathione pathway. It has been shown that the addition of
      glyoxalase I (GLO-I) and reduced glutathione (GSH) to PDF effectively eliminates
      GDP. We have therefore examined the GLO-I/GSH system in HPMC and assessed the
      impact of GLO-I/ GSH-treated PDF on the viability and function of HPMC. METHODS:
      Heat-sterilized PDF (H-PDF) was incubated in the presence or absence of GLO-I and
      GSH for 1 hour at 37 degrees C, and then mixed with an equal volume of serum-free
      M199 medium and applied to HPMCin culture. After 24 hours, HPMC were assessed for
      viability, the release of interleukin-6, GLO-I activity, and cellular
      glutathione. The effects were compared to those exerted by filter-sterilized PDF
      (F-PDF), which was devoid of GDP. RESULTS: Exposure of HPMC to H-PDF resulted in
      reduced GLO-I activity, GSH depletion, and a decrease in cell viability.
      Pretreatment of H-PDF with either a combination of GLO-I and GSH or GSH alone
      markedly reduced inhibitory effects of H-PDF toward HPMC, as measured by cell
      viability and inter-Leukin-6 generation. Exposure of HPMC to the GSH precursor L
      2-oxothiazolidine-carboxylic acid increased cellular GSH and prevented the loss
      of GLO-I activity in response to H-PDF. CONCLUSIONS: Exposure to conventional GDP
      rich PDF impairs the activity of the glyoxalase/glutathione system in HPMC.
      Pretreatment of PDF with GSH or replenishment of cellular GSH protects HPMC
      against GDP-mediated toxicity.

PMID- 16623436
TI  - Gabapentin in treatment of restless legs syndrome in peritoneal dialysis
      patients.

PMID- 16623437
TI  - Spontaneous fracture of the intraperitoneal portion of a PD catheter.

PMID- 16623435
TI  - The success story of peritoneal dialysis in Romania: analysis of differences in
      mortality by dialysis modality and influence of risk factors in a national
      cohort.
AB  - BACKGROUND: This report describes the status of renal replacement therapy (RRT),
      particularly continuous ambulatory peritoneal dialysis (CAPD), in Romania (a
      country with previously limited facilities), outlines the fast development rate
      of CAPD, and presents national changes in a European context. METHODS: Trends in
      the development of RRT were analyzed in 2003 on a national basis using annual
      center questionnaires from 1995 to 2003. Survival data and prognostic risk
      factors were calculated retrospectively from a representative sample of 2284
      patients starting RRT between 1 January 1995 and 31 December 2001 (44% of the
      total RRT population investigated). RESULTS: The annual rate of increase in the
      number of RRT patients (11%) was supported mainly by an exponential development
      of the CAPD population (+600%); the hemodialysis (HD) growth rate was stable
      (+33%) and renal transplantation had a marginal contribution. The characteristics
      of both HD and PD incident patients changed according to current European
      epidemiology (increasing age and prevalence of diabetes and
      nephroangiosclerosis). There were significant differences between PD and HD
      incident populations, PD patients being significantly older and having a higher
      prevalence of diabetic nephropathy and baseline comorbidities, probably
      reflecting different inclusion policies. The estimated overall survival of RRT
      patients in Romania was 90.6% at 1 year [confidence interval (CI) 89.4 - 91.8]
      and 62.2% at 5 years (CI 59.4 - 65.0). The initial treatment modality did not
      significantly influence patients' survival. There was no difference in unadjusted
      technique survival during the first 2 years; afterwards, there was a clear
      advantage for HD, with more patients being transferred from PD to HD. Several
      factors seemed to significantly and negatively influence PD patients' survival
      (Cox regression analysis): male gender, lack of predialysis erythropoietin
      treatment, and initial comorbidities. Stratified analysis to discover the
      influence of these factors on patients' survival revealed that HD was associated
      with an increased risk of death in the younger nondiabetic end-stage renal
      disease population, regardless of other coexisting comorbid conditions. However,
      in older patients (>65 years) and in diabetics, regardless of the presence or
      absence of associated comorbid conditions, there was no significant difference in
      death rates between HD and PD patients. CONCLUSIONS: We report an impressive
      quantitative and qualitative development of CAPD in one of the rapidly growing
      Central and Eastern Europe countries. CAPD should be the method of choice for
      young nondiabetic end-stage renal disease patients. Improvement in predialysis
      nephrologic care and in transplantation rates is required to further ensure the
      ultimate success of the Romanian PD program.

PMID- 16623438
TI  - Creatinine measurements by the Jaffe method in different peritoneal dialysis
      fluids exhibit wide variation.

PMID- 16623439
TI  - Sterile peritonitis and culture-negative peritonitis: do the two terms mean the
      same thing?

PMID- 16623440
TI  - [A practicing physician's view on obesity].
AB  - Overweight and obesity are worldwide problems, its health and psychosocial burden
      on the individual and on society are tremendous. Diagnosing obesity is rather
      easy, and is based on simple anthropometric measurements, such as body weight,
      height and waist circumference. The different classes of obesity are determined
      by body mass index, which, together with waist circumference and comorbid
      conditions and other risk factors determine the individual risk for mortality and
      morbidity. Obesity is due to genetic and environmental factors, mainly is the
      consequence of excess calorie intake and sedentary lifestyle. The fat mass of the
      body is under neuroendocrine control, the central controller is the hypothalamus.
      Leptin, produced by adipocytes in proportion to fat mass, is the afferent signal
      to the hypothalamus. Decreasing or increasing levels of leptin result in orexigen
      and anorexigen neurotransmission, which mediate efferent activation towards food
      consumption and energy storage, or towards food restriction and energy
      expenditure, respectively. The balance of these events and/or the ,set point" of
      the controller--if leptin resistance is present--is shifted towards higher
      body/fat mass in obesity. Management of obesity is complex, however, in all
      stages of obesity lifestyle changes are mandatory--including diet, exercise and
      behavior modification. Pharmacotherapy might be needed if lifestyle changes alone
      do not result an acceptable weight loss. For the long-term treatment of obesity
      sibutramin and orlistat are the available approved drugs. In case of morbid
      obesity (body mass index > 40 kg/m2, or > 35 kg/m2 plus comorbid conditions and
      other risk factors) surgery might be the treatment of choice. There are different
      surgical methods, among those a widely used method nowadays is the laparoscopic
      adjustable gastric banding procedure.

PMID- 16623442
TI  - [The role of antioxidants in prevention].
AB  - The imbalance between free radical formation and the mechanisms involved in
      eliminating them results in oxidative stress which lies at the baseline of many
      diseases. There are many pathological conditions that can be prevented or even be
      cured by the application of antioxidants. Food containing plenty of natural
      antioxidants is very important in the maintenance of health and in the prevention
      of many illnesses. In some diseases supplementation of antioxidants in the proper
      form and dosage may be irrelevant. According to nutrigenomics the biologically
      active components of nutrition, including antioxidants, have an influence on the
      body in every single cell at all levels. Therefore the quality of nutrients is
      one of the important factors determining the appropriate cell function.

PMID- 16623441
TI  - [Immunology of HCV infection: the causes of impaired cellular immune response and
      the effect of antiviral treatment].
AB  - BACKGROUND: The outcome of HCV infection and the response to antiviral treatment
      depend on both viral and host factors. Host immune response contributes not only
      to viral control, clinical recovery and protective immunity, but also to chronic
      hepatitis and liver cirrhosis. Establishing immunological status and identifying
      pretreatment immunological factors associated with better response to therapy
      might be of importance in the understanding of the successful immune response and
      in the future of combination therapy to HCV infection. AIMS: The authors
      delivered a review on the immunology of HCV infection and characterized the cause
      of impaired cellular immune response in chronic HCV infection. Natural killer
      (NK) cell activity, perforin and the inhibitory CD81 HCV co-receptor expression,
      and Th1/Th2 cytokine production of the monocytes and lymphocytes have been
      investigated. PATIENTS AND METHODS: 42 patients with chronic hepatitis C, out of
      them 25 being on interferon (PEG-IFN) + ribavirin (RBV) therapy, 12 sustained
      virological responders, 26 HCV carriers with normal transaminase values and 22
      healthy controls were studied. NK cell activity, perforin and CD81 expression,
      the IFNgamma, TNFalpha, IL-2 (Th1) and IL-4, IL-6, IL-10 (Th2) production of LPS
      stimulated monocytes and PMA + ionomycine stimulated lymphocytes were measured by
      flow-cytometry. RESULTS: In patients with chronic hepatitis C we demonstrated
      decreased NK cell activity associated with increased CD81 expression. The
      perforin expression of lymphocytes was also impaired in HCV patients. The
      pretreatment capacity of the macrophages to produce TNFalpha was predictive for
      sustained virological response. This increased TNFalpha production of the
      monocytes counteracted the observed impaired Th1 type cytokine production of the
      lymphocytes. IL-10 and IL-4 production showed positive correlation with HCV RNA
      levels, and negative correlation with histological activity index was noted. PEG
      IFN + RBV treatment increased NK activity, perforin expression, Th1 type cytokine
      production of thr lymphocytes and downregulated CD81 expression inducing
      effective cellular immune response against HCV. The author's results provide
      further data to understand the causes of impaired cellular immune response in
      chronic HCV hepatitis and may be useful in the developement of immunotherapy as
      an adjunctive treatment to cure patients with chronic hepatitis C.

PMID- 16623443
TI  - [Ganciclovir treatment of congenital cytomegalovirus infection].
AB  - The authors present the cases of two infants with congenital cytomegalovirus
      infection, who to the best of the authors' knowledge were the first ones to
      receive ganciclovir treatment in Hungary. Both infants were treated for
      symptomatic congenital cytomegalovirus infection affecting the central nervous
      system. Ganciclovir was given intravenously in two phases, for a total of 4 and 6
      weeks, in a daily dose of 5-10 mg/kg. Diagnosis of infection and follow-up of
      treatment efficacy was based on the quantitative assessment by PCR assay of viral
      nucleic acid in blood and urine samples. Treatment resulted in substantial
      reduction of viral copy numbers in both infants' blood and urine samples.
      Improvement in the biochemical markers of disease activity was accompanied with
      spectacular improvement of clinical symptoms in the infant with severe liver
      involvement. Following the treatment viral loads increased in both infant but
      clinical symptoms did not reoccur. In one patient a considerable improvement of
      hearing loss was observed. The authors' first results indicate that ganciclovir
      treatment of neonatal cytomegalovirus infection represents a promising approach
      in preventing the progression of the disease and in ameliorating the
      consequences.

PMID- 16623444
TI  - [Kaposi-sarcoma].

PMID- 16623450
TI  - Low-dimensional manifolds in reaction-diffusion equations. 1. Fundamental
      aspects.
AB  - The approach to equilibrium for systems of reaction-diffusion equations on
      bounded domains is studied geometrically. It is shown that equilibrium is
      approached via low-dimensional manifolds in the infinite-dimensional function
      space for these dissipative, parabolic systems. The fundamental aspects of this
      process are mapped out in some detail for single species cases and for two
      species cases where there is an exact solution. It is shown how the manifolds
      reduce the dimensionality of the system from infinite dimensions to only a few
      dimensions.

PMID- 16623451
TI  - Low-dimensional manifolds in reaction-diffusion equations. 2. Numerical analysis
      and method development.
AB  - Calculations are undertaken to study the approach to equilibrium for systems of
      reaction-diffusion equations on bounded domains. It is demonstrated that a number
      of systems approach equilibrium along attractive low-dimensional manifolds over
      significant ranges of parameter space. Numerical methods for generating the
      manifolds are adapted from methods that were developed for systems of ordinary
      differential equations. The truncation of the infinite spectrum of the partial
      differential equations makes it necessary to devise a new version of one of these
      methods, the well-known algorithm of Maas and Pope.

PMID- 16623452
TI  - Ab initio treatment of the chemical reaction precursor complex Cl(2P)-HF. 1.
      Three-dimensional diabatic potential energy surfaces.
AB  - The three adiabatic potential surfaces of the Cl(2P)-HF complex that correlate
      with the 2P ground state of the Cl atom were calculated with the ab initio
      RCCSD(T) method (partially spin-restricted coupled cluster theory including
      single and double excitations and perturbative correction for the triples). With
      the aid of a geometry-dependent diabatic mixing angle, calculated by the complete
      active space self-consistent field (CASSCF) and multireference configuration
      interaction (MRCI) methods, these adiabatic potential surfaces were converted to
      a set of four distinct diabatic potential surfaces required to define the full 3
      x 3 matrix of diabatic potentials. Each of these diabatic potential surfaces was
      expanded in terms of the appropriate spherical harmonics in the angle theta
      between the HF bond axis r and the Cl-HF intermolecular axis R. The dependence of
      the expansion coefficients on the Cl-HF distance R and the HF bond length r(HF)
      was fit to an analytic form. The strongest binding occurs for the hydrogen-bonded
      linear Cl-HF geometry, with D(e) = 676.5 cm(-1) and R(e) = 6.217 a0 when r(HF) =
      r(e) = 1.7328 a0. This binding energy D(e) depends strongly on r(HF), with larger
      r(HF) causing stronger binding. An important contribution to the binding energy
      is provided by the interaction between the quadrupole moment of the Cl(2P) atom
      and the dipole of HF. In agreement with this electrostatic picture, the ground
      state of linear Cl-HF is a 2-fold degenerate electronic Pi state. For the linear
      Cl-FH geometry the states are in opposite order, i.e., the Sigma state is lower
      in energy than the Pi state. The following paper in this issue describes full
      three-dimensional computations of the bound states of the Cl-HF complex, based on
      the ab initio diabatic potentials of this paper.

PMID- 16623453
TI  - Ab initio treatment of the chemical reaction precursor complex Cl(2P)-HF. 2.
      Bound states and infrared spectrum.
AB  - Bound energy levels and properties of the Cl(2P)-HF complex were obtained from
      full three-dimensional (3D) calculations, with the use of the ab initio computed
      diabatic potential surfaces from the preceding paper and the inclusion of spin
      orbit coupling. For a better understanding of the dynamics of this complex we
      also computed a 2D model in which the HF bond length r was frozen at the
      vibrationally averaged values r0 and r1 and a 2 + 1D model in which the 3D
      potentials were averaged over the v(HF) = 0 and v(HF) = 1 vibrational wave
      functions of free HF. Also 1D calculations were made in which both r and the Cl
      HF distance R were frozen. The complex is found to have the linear hydrogen
      bonded Cl-HF structure, with ground-state quantum numbers J = 3/2 for the overall
      angular momentum and /omega/ = 3/2 for its projection on the intermolecular axis
      R. The binding energy is D0 = 432.25 cm(-1) for v(HF) = 0 and D0 = 497.21 cm(-1)
      for v(HF) = 1. Bending modes with /omega/ = 1/2 and /omega/ = 5/2 are split by
      the Renner-Teller effect, since the electronic ground state is a degenerate 2pi
      state. A series of intermolecular (R) stretch modes was identified. Rotational
      constants and e-f parity splittings were extracted from the levels computed for J
      = 1/2 to 7/2. The computed red shift of the HF stretch frequency of 64.96 cm(-1)
      and the 35Cl-37Cl isotope shift of 0.033 cm(-1) are in good agreement with the
      values of 68.77 and 0.035 cm(-1) obtained from the recent experiment of Merritt
      et al. (Phys. Chem. Chem. Phys. 2005, 7, 67), after correction for the effect of
      the He nanodroplet matrix in which they were measured.

PMID- 16623454
TI  - Quantum mechanical study of the correlation of attack and recoil angles for the
      Cl + H2 reaction using the stereodirected and discrete variable representations
      on two potential energy surfaces.
AB  - The zero total angular momentum (J = 0) S matrix elements, calculated using a
      time-dependent wave packet method for the Cl (2P) + H2 reaction on two different
      potential energy surfaces, have been matrix transformed to the stereodirected and
      Gauss-Legendre discrete variable representations. Although the results in the two
      representations are (as expected) quantitatively different with respect to the
      angular selectivity and specificity of the reactive process, the qualitative
      similarity has allowed us to draw for the first time conclusions with respect to
      some characteristics of the potential energy surface.

PMID- 16623455
TI  - A nested molecule-independent neural network approach for high-quality potential
      fits.
AB  - It is shown that neural networks (NNs) are efficient and effective tools for
      fitting potential energy surfaces. For H2O, a simple NN approach works very well.
      To fit surfaces for HOOH and H2CO, we develop a nested neural network technique
      in which we first fit an approximate NN potential and then use another NN to fit
      the difference of the true potential and the approximate potential. The root-mean
      square error (RMSE) of the H2O surface is 1 cm(-1). For the 6-D HOOH and H2CO
      surfaces, the nested approach does almost as well attaining a RMSE of 2 cm(-1).
      The quality of the NN surfaces is verified by calculating vibrational spectra.
      For all three molecules, most of the low-lying levels are within 1 cm(-1) of the
      exact results. On the basis of these results, we propose that the nested NN
      approach be considered a method of choice for both simple potentials, for which
      it is relatively easy to guess a good fitting function, and complicated (e.g.,
      double well) potentials for which it is much harder to deduce an appropriate
      fitting function. The number of fitting parameters is only moderately larger for
      the 6-D than for the 3-D potentials, and for all three molecules, decreasing the
      desired RMSE increases only slightly the number of required fitting parameters
      (nodes). NN methods, and in particular the nested approach we propose, should be
      good universal potential fitting tools.

PMID- 16623456
TI  - Quantum statistical study of O + O2 isotopic exchange reactions: cross sections
      and rate constants.
AB  - Using a wave packet based statistical model, we compute cross sections and
      thermal rate constants for various isotopic variants of the O + O2 exchange
      reaction on a recently modified ab initio potential energy surface. The
      calculation predicts a highly excited rotational distribution and relatively cold
      vibrational distribution for the diatomic product. A small but important
      threshold effect was identified for the (16)O + 18O2 reaction, which is suggested
      to contribute to the experimentally observed negative temperature dependence of
      the rate ratio, k(18O + 16O2)/k(16O + 18O2). Despite reasonable agreement with
      quasiclassical trajectory results, however, the calculated thermal rate constants
      are smaller than experimental measurements by a factor from 2 to 5. The
      experimentally observed negative temperature dependence of the rate constants is
      not reproduced. Possible reasons for the theory-experiment discrepancies are
      discussed.

PMID- 16623457
TI  - Quantum molecular dynamics study of the reaction of O2 with HOCO.
AB  - The reaction of O2 with HOCO has been studied by using an ab initio direct
      dynamics method based on the UB3PW91 density functional theory. Results show that
      the reaction can occur via two mechanisms: direct hydrogen abstraction and an
      addition reaction through a short-lived HOC(O)O2 intermediate. The lifetime of
      the intermediate is predicted to be 660 +/- 30 fs. Although it is an activated
      reaction, the activation energy is only 0.71 kcal/mol. At room temperature, the
      obtained thermal rate coefficient is 2.1 x 10(-12) cm3 molecule(-1) s(-1), which
      is in good agreement with the experimental results.

PMID- 16623458
TI  - Assignment and extraction of dynamics of a small molecule with a complex
      vibrational spectrum: thiophosgene.
AB  - The dispersed fluorescence spectrum of the ground electronic state of
      thiophosgene, SCCl2, is analyzed in a very complex region of vibrational
      excitation, 7000-9000 cm(-1). The final result is that most of the inferred
      excited vibrational levels are assigned in terms of approximate constants of the
      motion. Furthermore, each level is associated with a rung on a ladder of quantum
      states on the basis of common reduced dimension fundamental motions. The
      resulting ladders cannot be identified by any experimental means, and it is the
      interspersing in energy of their rungs that makes the spectrum complex even after
      the process of level separation into polyads. Van Vleck perturbation theory is
      used to create polyad constants of the motion and a spectroscopic Hamiltonian
      from a potential fitted to experimental data. The eigen functions of this
      spectroscopic Hamiltonian are rewritten as semiclassical wave functions and
      transformed to a representation that allows us to analyze and assign the spectra
      with no other work other than to utilize concepts from nonlinear dynamics.

PMID- 16623459
TI  - Structural transitions and melting in LJ(74-78) Lennard-Jones clusters from
      adaptive exchange Monte Carlo simulations.
AB  - Phase changes in Lennard-Jones (LJ) clusters containing between 74 and 78 atoms
      are investigated by means of exchange Monte Carlo simulations in the canonical
      ensemble. The replica temperatures are self-adapted to facilitate the
      convergence. Although the 74- and 78-atom clusters have icosahedral global
      minima, the clusters with 75-77 atoms have decahedral ground-state structures and
      they undergo a structural transition to icosahedral minima before melting. The
      structural transitions are characterized by quenching and by looking at the Q4
      and Q6 orientational bond order parameters. The transition temperatures are
      estimated to be 0.114, 0.065, and 0.074 reduced units for LJ75, LJ76, and LJ77,
      respectively. These values, their ordering and the associated latent heats are
      compared with other estimates based on the harmonic superposition approach.

PMID- 16623460
TI  - A self-consistent field quantum hydrodynamic approach for molecular clusters.
AB  - We present a novel self-consistent orbital-free method useful for quantum
      clusters. The method uses a hydrodynamical approach based on the de Broglie-Bohm
      description of quantum mechanics to satisfy an orbital-free density functional
      like Euler-Lagrange equation for the ground state of the system. In addition, we
      use an information theoretical approach to obtain the optimal density function
      derived from a series of statistical sample points in terms of density
      approximates. These are then used to calculate an approximation to the quantum
      force in the hydrodynamic description. As a demonstration of the utility and
      flexibility of the approach, we compute the lowest-energy structures for small
      rare-glass clusters of argon and neon with 4, 5, 13, and 19 atoms. Extension to
      more complex systems is straightforward.

PMID- 16623461
TI  - Photochemical processes induced by vibrational overtone excitations: dynamics
      simulations for cis-HONO, trans-HONO, HNO3, and HNO3-H2O.
AB  - Photochemical processes in HNO3, HNO3-H2O, and cis- and trans-HONO following
      overtone excitation of the OH stretching mode are studied by classical trajectory
      simulations. Initial conditions for the trajectories are sampled according to the
      initially prepared vibrational wave function. Semiempirical potential energy
      surfaces are used in "on-the-fly" simulations. Several tests indicate at least
      semiquantitative validity of the potential surfaces employed. A number of
      interesting new processes and intermediate species are found. The main results
      include the following: (1) In excitation of HNO3 to the fifth and sixth OH
      stretch overtone, hopping of the H atom between the oxygen atoms is found to take
      place in nearly all trajectories, and can persist for many picoseconds. H-atom
      hopping events have a higher yield and a faster time scale than the
      photodissociation of HNO3 into OH and NO2. (2) A fraction of the trajectories for
      HNO3 show isomerization into HOONO, which in a few cases dissociates into HOO and
      NO. (3) For high overtone excitation of HONO, isomerization into the weakly bound
      species HOON is seen in all trajectories, in part of the events as an
      intermediate step on the way to dissociation into OH + NO. This process has not
      been reported previously. Well-established processes for HONO, including cis
      trans isomerization and H hopping are also observed. (4) Only low overtone levels
      of HNO3-H2O have sufficiently long liftimes to be spectrocopically relevant.
      Excitation of these OH stretching overtones is found to result in the
      dissociation of the cluster H hopping, or dissociation of HNO3 does not take
      place. The results demonstrate the richness of processes induced by overtone
      excitation of HNO(x) species, with evidence for new phenomena. Possible relevance
      of the results to atmospheric processes is discussed.

PMID- 16623462
TI  - Molecular dynamics simulation of laser desorption of a fragment of protein kinase
      A from two MALDI matrices.
AB  - We have carried out molecular dynamics simulations to study the desorption of a
      dephosphorylated fragment of protein kinase A from two matrices, sinapic acid
      (SA) and 2,5-dihydroxybenzoic acid (DHB), after laser excitation. We have
      examined the results as a function of the laser fluence and of the burial depth
      of the guest peptide in the matrices. In most cases, we found that the energy
      transferred from the matrix to the guest peptide was not sufficiently large to
      fragment the peptide. Exceptions occurred when the peptide was more buried. This
      finding suggested that protein analytes might be less likely to break into
      smaller fragments if they were placed closer to the surface of the matrix. We
      have also examined how likely the guest peptide could form small clusters with
      the matrix molecules and found that the results depended on the degree of burial
      of the peptide, on the laser fluence, and on which matrix was used. Generally,
      stable clusters were more likely to be formed for guest peptides that were more
      buried, at a lower laser fluence, and in the SA rather than the DHB matrix. In
      addition, we found that the DHB matrix was broken down more easily by the laser
      than the SA matrix.

PMID- 16623463
TI  - Time-dependent sensitivity analysis of biological networks: coupled MAPK and PI3K
      signal transduction pathways.
AB  - Sensitivity analysis has been widely used in the studies of complicated chemical
      reaction and biological networks, for example, in combustion studies and
      metabolic control analysis of pathways. In the latter cases, the responses of
      system properties at steady states with respect to changes of parameters, such as
      initial concentrations and rate constants, are often expressed as sensitivities.
      Besides steady-state sensitivities, time-dependent sensitivities should be
      useful; however, the explicit use of them in analyzing complicated biological
      systems has so far been limited. Using the coupled mitogen activated protein
      kinase (MAPK)-phophatidylinoisitol 3'-kinase (PI3K) system of the Ras pathways,
      known to be involved in about 30% of human cancers, as an example, we show that
      time-dependent sensitivities are useful for the studies of complex biological
      systems. They provide, for example, the following information: (a) multiple time
      scales existing in a complex system involving cross-talks and feedback loops; (b)
      the signs and strengths of responses to perturbations (as system complication
      increases, the signs of global responses are not always easily determined; for
      example, response may change sign more than once as time evolves); (c) beyond
      concentration dynamics, sensitivities revealing further details about the
      intricate dynamics and the effects of the cross-talks; (d) ranking of
      vulnerability of nodes of a biological network using integrated sensitivity-a
      first step toward the identification of drug targets; (e) reduced sensitivity
      serving as a measure of the stability or robustness of pathways. Our results
      indicate that the role of the PI3K branch in the coupled pathways is to enhance
      the robustness of the MAPK pathway. More importantly, they demonstrate that time
      dependent sensitivity analysis can be a valuable tool in system biology.

PMID- 16623464
TI  - Photodissociation of HBr. 1. Electronic structure, photodissociation dynamics,
      and vector correlation coefficients.
AB  - Ab initio potential energy curves, transition dipole moments, and spin-orbit
      coupling matrix elements are computed for HBr. These are then used, within the
      framework of time-dependent quantum-mechanical wave-packet calculations, to study
      the photodissociation dynamics of the molecule. Total and partial integral cross
      sections, the branching fraction for the formation of excited-state bromine atoms
      Br(2P(1/2)), and the lowest order anisotropy parameters, beta, for both ground
      and excited-state bromine are calculated as a function of photolysis energy and
      compared to experimental and theoretical data determined previously. Higher order
      anisotropy parameters are computed for the first time for HBr and compared to
      recent experimental measurements. A new expression for the Re[a1(3) (parallel,
      perpendicular)] parameter describing coherent parallel and perpendicular
      production of ground-state bromine in terms of the dynamical functions is given.
      Although good agreement is obtained between the theoretical predictions and the
      experimental measurements, the discrepancies are analyzed to establish how
      improvements might be achieved. Insight is obtained into the nonadiabatic
      dynamics by comparing the results of diabatic and fully adiabatic calculations.

PMID- 16623465
TI  - Photodissociation of cyclobutyl bromide at 234 nm studied using velocity map
      imaging.
AB  - This study investigates the 234 nm photodissociation dynamics of cyclobutyl
      bromide using a two-dimensional photofragment velocity imaging technique. The
      spin-orbit ground- and excited-state Br(2P) atoms are state-selectively detected
      via [2+1] resonance enhanced multiphoton ionization (REMPI), whereas the
      cyclobutyl radicals are ionized using 157 nm laser light. The Br(2P(3/2)) and the
      Br(2P(1/2)) atoms and their c-C4H7 radical cofragments evidence a single-peaked,
      Gaussian-shaped translational energy distribution ranging from approximately 14
      to approximately 39 kcal/mol and angular distributions with significant parallel
      character. The Br(2P(1/2))/ Br(2P(3/2)) spin-orbit branching ratio is determined
      to be 0.11 +/- 0.07 by momentum match between the Br(2P) photofragments and the
      recoiling c-C4H7 fragments, assuming a uniform photoionization probability of the
      c-C4H7 radicals with an internal energy range of 10-35 kcal/mol. The REMPI line
      strength ratio for the detection of Br(2P(3/2)) and Br(2P(1/2)) atoms at 233.681
      and 234.021 nm, respectively, is therefore derived to be 0.10 +/- 0.07. The
      measured recoil kinetic energies of the c-C4H7 radicals, and the resulting
      distribution of internal energies, indicates some of the radicals are formed with
      total internal energies above the barrier to isomerization and subsequent
      dissociation, but our analysis indicates they may be stable due to the
      substantial fraction of the internal energy which is partitioned to rotational
      energy of the radicals.

PMID- 16623466
TI  - Hyperfine coupling constants of the azafullerenes C19N, C59N, C69N, and C75N.
AB  - The isomers of the nitrogen-substituted fullerenes (azafullerenes) C19N, C59N,
      C69N, and C75N are examined using all-electron Gaussian atomic orbital basis
      density functional theory, to determine the doublet radical geometries and
      hyperfine coupling constants. We find that the inaccuracy of previously
      calculated hyperfine coupling constants of C59N resulted from a poor treatment of
      the geometry optimization. We find that UB3LYP minimization of the radical
      geometry in the 6-31G basis, followed by single-point evaluation of the hyperfine
      constants in which an expanded basis is used on the atomic sites of interest,
      forms an efficient compromise between computational cost and accuracy with
      respect to experimental hyperfine constants. Using this approach, we assign the
      hyperfine signals observed in experiments on the C69N radical by calculating the
      hyperfine coupling constants for all five of the isomers and examine the electron
      spin density distribution. Finally, we present predicted hyperfine coupling
      constants for the isomers of C19N and C75N for use in the interpretation of
      future experiments.

PMID- 16623467
TI  - Excited States of weakly bound bosonic clusters: discrete variable representation
      and quantum Monte Carlo.
AB  - We compare two approaches for the accurate calculation of the energy levels of
      weakly bound boson trimers. The first approach is based on correlation function
      Monte Carlo employing optimized trial functions, while the second approach is
      based on the discrete variable representation. A trimer with atoms of half the
      mass of neon is used as a test problem for benchmark calculations. The two
      approaches yield identical results, within error bars, for all the J = 0 energy
      levels below the dissociation threshold. The relative merits of the two
      techniques are discussed, and a perspective is given for extension to larger
      clusters.

PMID- 16623468
TI  - Calculating multidimensional discrete variable representations from cubature
      formulas.
AB  - Finding multidimensional nondirect product discrete variable representations
      (DVRs) of Hamiltonian operators is one of the long standing challenges in
      computational quantum mechanics. The concept of a "DVR set" was introduced as a
      general framework for treating this problem by R. G. Littlejohn, M. Cargo, T.
      Carrington, Jr., K. A. Mitchell, and B. Poirier (J. Chem. Phys. 2002, 116, 8691).
      We present a general solution of the problem of calculating multidimensional DVR
      sets whose points are those of a known cubature formula. As an illustration, we
      calculate several new nondirect product cubature DVRs on the plane and on the
      sphere with up to 110 points. We also discuss simple and potentially very useful
      finite basis representations (FBRs), based on general (nonproduct) cubatures.
      Connections are drawn to a novel view on cubature presented by I. Degani, J.
      Schiff, and D. J. Tannor (Num. Math. 2005, 101, 479), in which commuting
      extensions of coordinate matrices play a central role. Our construction of DVR
      sets answers a problem left unresolved in the latter paper, namely, the problem
      of interpreting as function spaces the vector spaces on which commuting
      extensions act.

PMID- 16623469
TI  - Water dimers in the atmosphere III: equilibrium constant from a flexible
      potential.
AB  - We present new results for the water dimer equilibrium constant K(p)(T) in the
      range 190-390 K, using a flexible potential energy surface fitted to
      spectroscopical data. The increased numerical complexity due to explicit
      consideration of the monomer vibrations is handled via an adiabatic (6 + 6)d
      decoupling between intra- and intermolecular modes. The convergence of the
      canonical partition function of the dimer is ensured by computing all energy
      levels up to dissociation for total angular momentum values J = 0-5 and using an
      extrapolation scheme to higher values. The newly calculated values for K(p)(T)
      are in very good agreement with available experimental data at room temperature.
      At higher temperatures, an analysis of the convergence of the partition function
      reveals that quasi-bound states are likely to contribute to the equilibrium
      constant. Additional thermodynamical quantities (deltaG, deltaH, deltaS, and
      C(p)) have also been determined and fit to quadratic expressions a + bT + cT2.

PMID- 16623470
TI  - Comparison of perturbative and variational treatments of molecular vibrations:
      application to the vibrational spectrum of HFCO up to 8000 cm(-1).
AB  - We calculated highly excited states of the HFCO molecule, comparing results from
      two methods. In the first method, Van Vleck perturbation theory is used to
      transform away all off-diagonal couplings except those between nearly degenerate
      states. This perturbative transformation leads to a matrix representation where
      eigenvalues are obtained with relatively small matrices. In the second method,
      variational eigenvalues are obtained by combining the Jacobi-Wilson approach with
      the block-Davidson scheme. The key ingredient here is a prediagonalized
      perturbative scheme applied to a subspace of a curvilinear normal-mode basis set.
      Comparisons of the two methods provide a critical test of the less time-consuming
      perturbation theory. Two different coordinate sets are used to test the
      sensitivity of the results to coordinate choice. Perturbation theory also
      requires a polynomial fit to the potential. The implications of this restriction
      are investigated.

PMID- 16623471
TI  - Tunneling splitting of energy levels and rotational constants in the vinyl
      radical C2H3.
AB  - The instanton theory newly implemented by two of the authors (G.V.M. and H.N.) is
      applied to hydrogen tunneling transfer in a vinyl radical. The converged
      instanton trajectory is found on the CCSD(T)/aug-cc-pVTZ level of an ab initio
      potential energy surface. The calculated ground-state energy splitting agrees
      with the recent high-resolution experimental data within 3% of discrepancy. The
      semiclassical wave function is used to estimate the splitting of the principal
      rotational constants of the radical.

PMID- 16623472
TI  - Coupled-states statistical investigation of vibrational and rotational relaxation
      of OH(2pi) by collisions with atomic hydrogen.
AB  - We report state-to-state cross sections and thermal rate constants for
      vibrational and rotational relaxation of OH(2pi) by collision with H atoms. The
      cross sections are calculated by the coupled-states (CS) statistical method
      including the full open-shell character of the OH + H system. Four potential
      energy surfaces (PESs) ((1,3)A' and (1,3)A'') describe the interaction of
      OH(X2pi) with H atoms. Of these, three are repulsive, and one (1A') correlates
      with the deep H2O well. Consequently, rotationally and ro-vibrationally inelastic
      scattering of OH in collisions with H can occur by scattering on the repulsive
      PESs, in a manner similar to the inelastic scattering of OH by noble gas atoms,
      or by collisions which enter the H2O well and then reemerge. At 300 K, we predict
      large (approximately 1 x 10(-10) cm3 molecule(-1) s(-1)) vibrational relaxation
      rates out of both v = 2 and v = 1, comparable to earlier experimental
      observations. This anomalously fast relaxation results from capture into the H2O
      complex. There exists a significant propensity toward formation of OH in the
      pi(A') lambda-doublet level. We also report state-resolved cross sections and
      rate constants for rotational excitation within the OH v = 0 manifold.
      Collisional excitation from the F1 to the F2 spin-orbit manifold leads to an
      inverted lambda-doublet population.

PMID- 16623473
TI  - Zero-point energy constraint in quasi-classical trajectory calculations.
AB  - A method to constrain the zero-point energy in quasi-classical trajectory
      calculations is proposed and applied to the Henon-Heiles system. The main idea of
      this method is to smoothly eliminate the coupling terms in the Hamiltonian as the
      energy of any mode falls below a specified value.

PMID- 16623474
TI  - Photoelectron spectra of Ar(n).(IHI)- (n = 0-6, 12, 20), a theoretical study.
AB  - The effects of the introduction of argon atoms on the photoelectron (PE) spectra
      of Ar(n).(IHI)- with n = 0-6, 12, and 20 are investigated. Time-independent
      quantum simulations of the spectra using a rigid cage approximation and allowing
      the motion of the IHI core are performed. As in our previous classical studies on
      this system, we find an increase in the confinement of the hydrogen atom motion
      as the number of argon atoms is increased. Comparison of the quantum and
      classical descriptions of this confinement provides evidence of the importance of
      quantum mechanical effects in this system. Three approaches are used to calculate
      the spectrum of the bare (IHI)- system. Excellent agreement is found between the
      simulated peaks in the = 2 region using a full three-dimensional quantum
      simulation of the PE spectrum, those from the corresponding experimental
      threshold photodetachment spectrum and those obtained by employing an adiabatic
      separation of the motions of the hydrogen and the iodine atoms. This provides
      further confirmation that these peaks are the result of motions of the iodine
      atoms. Simulations of the Ar(n).(IHI)- PE spectra show a shift of the spectra to
      lower electron kinetic energies as the number of argon atoms is increased.
      Similar shifts are found in the experimental spectra and in our previous study of
      this system using classical trajectory simulations. It is also found that the I-I
      motion mainly affects the spectrum features, whereas the progressions associated
      with hindered rotor transitions are less affected. Finally, an increase in the
      intensity of the = 0 peak and an accumulation of transitions in the low-frequency
      hindered rotor region with increasing number of argon atoms are observed.

PMID- 16623475
TI  - Interactions of 2P atoms with closed-shell diatomic molecules: alternative
      diabatic representations for the electronic anisotropy.
AB  - The matrices of electrostatic and spin-orbit Hamiltonians for the system of a 2P
      atom interacting with a closed shell diatomic molecule in uncoupled, coupled, and
      complex-valued representations for electronic diabatic basis functions are
      rederived, and the unitary transformations connecting them are given explicitly.
      The links to previous derivations are established and existing inconsistencies
      are identified and eliminated. It is proven that the block-diagonalization of a 6
      x 6 matrix of the electronic Hamiltonian is a result of using the basis functions
      with well-defined properties with respect to time reversal. Consideration of time
      reversal symmetry also enforces phase consistency relevant for applications to
      multisurface reactive scattering and photodetachment spectroscopy calculations,
      as well as for perspective studies of inelastic effects in cold and ultracold
      environments. These and further developments are briefly sketched.

PMID- 16623476
TI  - Ab initio calculation of the low-lying vibrational states of C2H2(A) in full
      dimensionality.
AB  - We report full-dimensional calculations of vibrational energies of trans-C2H2(A)
      using the code MULTIMODE and with a full-dimensional potential energy surface
      obtained by fitting singles and doubles coupled-cluster equations-of-motion (EOM
      CCSD) energies using a [3s 2p 1d] atomic natural orbital basis. The EOM-CCSD
      calculations were done with the code "ACES II". We compare the properties of the
      potential surface to previous calculations at the trans minimum and also compare
      the vibrational energies to experimental ones.

PMID- 16623477
TI  - HOCl Ro-vibrational bound-state calculations for nonzero total angular momentum.
AB  - The Lanczos homogeneous filter diagonalization method has been employed to
      compute the HOCl ro-vibrational states for a range of total angular momenta (J =
      0, 1, 5, 10, 11, 20, 30) on a newly developed ab initio potential energy surface
      by Nanbu et al. (J. Theor. Comput. Chem. 2002, 1, 263). For such computationally
      challenging calculations, a parallel computing strategy has been incorporated
      into our method to perform the matrix-vector multiplications. For the computed
      low bound states, a spectroscopic assignment has been made and the widely used
      approximate adiabatic rotation method has been tested for the broad range of
      total angular momenta for this deep-well system. Comparison of experimental
      results with exact quantum mechanical calculations for the selected far-infrared
      transitions involving the range of total angular momenta has been made possible
      for the first time.

PMID- 16623478
TI  - Fully quantum rovibrational calculation of the He(H2) bound and resonance states.
AB  - In a recent paper [J. Chem. Phys. 2005, 122, 124318], a full-dimensional quantum
      method, designed to efficiently compute the rovibrational states of triatomic
      systems with long-range interactions, was applied to the benchmark Li-(H2) ion
      molecule system. The method incorporates several key features in order to
      accurately represent the rovibrational Hamiltonian using only modestly sized
      basis sets: (1) exact analytical treatment of Coriolis coupling; (2) a single
      bend-angle basis for all rotational states; (3) phase space optimization of the
      vibrational basis; (4) G(4) symmetry adaptation of the rovibrational basis. In
      this paper, the same methodology is applied for the first time to a van der Waals
      complex system, He(H2). As in the Li-(H2) study, all of the rovibrational bound
      states, and a number of resonance states, are computed to very high accuracy
      (1/10,000 of a wavenumber or better). Three different isotopologues are
      considered, all of which are found to have a single bound state with a very low
      binding energy. Several extremely long-lived Feshbach resonances are also
      reported.

PMID- 16623479
TI  - Variational reduced-density-matrix theory applied to the potential energy
      surfaces of carbon monoxide in the presence of electric fields.
AB  - The variational optimization of the energy with respect to the two-electron
      reduced-density matrix (2-RDM), constrained by N-representability conditions, can
      determine the shape of molecular potential energy surfaces with useful accuracy.
      In this paper, we apply the 2-RDM method with a first-order optimization
      algorithm [Mazziotti, D. A. Phys. Rev. Lett. 2004, 93, 213001] to investigating
      the potential energy surfaces of carbon monoxide in the presence and absence of
      an electric field. Two beneficial characteristics of the 2-RDM method for
      computing potential energy surfaces include the following: (i) its ability to
      capture multireference effects without specifying any reference wave function or
      density matrix and (ii) its guarantee of a global energy minimum in the
      variational optimization. The 2-RDM method produces electronic ground-state
      energies with similar accuracy at equilibrium and nonequilibrium geometries in
      both the presence and the absence of the electric field. Computed dipole moments
      are similar in accuracy to the values from the computationally expensive
      configuration interaction with single, double, triple, and quadruple excitations.
      These surfaces have important applications in quantum molecular control theory.

PMID- 16623480
TI  - Rovibrational structures in floppy triatomics: distributed gaussian functions
      treatment for the Ne2H- system.
AB  - The full sequence of the bound states for a very floppy triatomic complex, Ne2H-
      in its ground electronic state, are initially computed for the rotationless
      situation and employing a variational approach that expands the total nuclear
      wave function over a large set of symmetry-adapted, distributed Gaussian
      functions and employs accurate atom-atom potential energy data. The results are
      tested for numerical convergence, compared with the behavior of both its diatomic
      fragments, Ne2 and NeH-, and further compared with the results for the Ne3 case.
      The computational analysis is extended to the production of the rotational
      constants for the very nonclassical ground state vibrational configuration by
      making use of the previous findings. The method is shown to provide us with
      several illuminating details on the nanoscopic internal dynamics of this very
      weakly bound quantum aggregate.

PMID- 16623481
TI  - Bessel-zernike discrete variable representation basis.
AB  - The connection between the Bessel discrete variable basis expansion and a
      specific form of an orthogonal set of Jacobi polynomials is demonstrated. These
      so-called Zernike polynomials provide alternative series expansions of suitable
      functions over the unit interval. Expressing a Bessel function in a Zernike
      expansion provides a straightforward method of generating series identities.
      Furthermore, the Zernike polynomials may also be used to efficiently evaluate the
      Hankel transform for rapidly decaying functions or functions with finite support.

PMID- 16623482
TI  - Ro-vibrational states of triplet H2D+.
AB  - We present rotational term values for J < or = 3 of the vibrational states with
      up to twofold excitation of H2D+ in the lowest electronic triplet state
      (a3sigma(u)+). The calculations were performed using the method of hyperspherical
      harmonics and our recent accurate double many-body expansion potential energy
      surface.

PMID- 16623483
TI  - General laser interaction theory in atom-diatom systems for both adiabatic and
      nonadiabatic cases.
AB  - This paper develops the general theory for laser fields interacting with
      bimolecular systems. In this study, we choose to use the multipolar gauge on the
      basis of gauge invariance. We consider both the adiabatic and nonadiabatic cases
      and find they produce similar interaction pictures. As an application of this
      theory, we present the study of rovibrational energy transfer in Ar + CO
      collisions in the presence of an intense laser field.

PMID- 16623484
TI  - A test of the continuous configuration time-dependent self-consistent field (CC
      TDSCF) method on the H + CH4 reaction.
AB  - The continuous configuration time-dependent self-consistent field (CC-TDSCF)
      method is employed to calculate the flux-flux autocorrelation functions for the H
      + CH4 reaction on the potential energy surface recently developed by Manthe and
      co-workers. We include up to 10 out of the total 12 degrees of freedom in our
      calculations, only with the doubly degenerate bending modes involving the motion
      of the hydrogens in nonreacting CH3 group excluded. Comparison of flux-flux
      autocorrelation functions obtained by using the exact dynamics method and the CC
      TDSCF method shows that the CC-TDSCF method is capable of producing very accurate
      results. Our calculations clearly reveal that the CC-TDSCF method is a powerful
      approximation quantum dynamics method. It allows us to partition a big problem
      into several smaller ones. By changing partition systematically, one can
      investigate the correlations between different degrees of freedom. By grouping
      modes with strong correlations together as a cluster, one can systematically
      improve accuracy of the result.

PMID- 16623485
TI  - Six-dimensional potential energy surface and rovibrational energies of the HCCN
      radical in the ground electronic state.
AB  - We report large-scale quantum mechanical calculations for the HCCN radical in its
      ground electronic state. A six-dimensional potential energy surface based on MR
      ACPF/cc-pVQZ ab initio energy points is developed and adjusted to reproduce
      experimental findings for and nu1 of HCCN. Rovibrational energy levels of HCCN
      and DCCN are computed for total rotational angular momentum J = 0-4 by making use
      of combined (functional + point wise) coordinate representations together with
      contraction schemes resulting from several diagonalization/truncation steps. The
      classical barrier to linearity is determined to be 287 cm(-1). Spectroscopic
      parameters are calculated for low lying states and compared with available
      experimental data. Energy patterns attributed to the nu4 bending mode and to the
      quasilinear nu5 bending mode are identified. It has been also found that nu2 and
      nu3 + (nu4(1),nu5(1))(0,0) are coupled in HCCN, while the mixing between nu3 and
      (2nu4(0), 2nu5(0))(0,0) is seen in DCCN.

PMID- 16623486
TI  - Quantum trajectory dynamics in arbitrary coordinates.
AB  - The quantum trajectory approach is generalized to arbitrary coordinate systems,
      including curvilinear coordinates. This allows one to perform an approximate
      quantum trajectory propagation, which scales favorably with system size, in the
      same framework as standard quantum wave packet dynamics. The trajectory
      formulation is implemented in Jacobi coordinates for a nonrotating triatomic
      molecule. Wave packet reaction probabilities are computed for the O(3P) + H2 -->
      OH + H reaction using the approximate quantum potential. The latter is defined by
      the nonclassical component of the momentum operator expanded in terms of linear
      and exponential functions. Unlike earlier implementations with linear functions,
      the introduction of the exponential function provides an accurate description of
      asymptotic dynamics for this system and gives good agreement of approximate
      reaction probabilities with accurate quantum calculations.

PMID- 16623487
TI  - Vibrational properties of disordered mono- and bilayers of physisorbed sulfur
      hexafluoride on Au(111).
AB  - We have examined the low-energy single-phonon vibrations of disordered mono- and
      bilayers of sulfur hexafluoride physisorbed on Au(111) with inelastic helium atom
      scattering. At monolayer coverages, SF6 exhibits a dispersionless Einstein mode
      at 3.6 +/- 0.4 meV. We observed two distinct overtones of this vibration as both
      creation and annihilation events at 7.1 +/- 0.7 meV and 10.9 +/- 1.4 meV,
      respectively. The overtones are harmonic multiples of the fundamental Einstein
      oscillation. Bilayers of SF6 exhibit a softer fundamental vibration with an
      excitation energy of 3.3 +/- 0.3 meV. This softening, due to the weaker SF6
      binding, also results in reduced overtone energies of 6.6 +/- 0.7 meV and 9.8 +/-
      0.6 meV. The disordered bilayer does not exhibit dispersion, indicating that the
      molecules are still behaving like Einstein oscillators and not beginning to act
      as bulk crystalline SF6. The results have improved our understanding of the
      adsorbate-substrate and interadsorbate interactions which govern the properties
      of this model molecular physisorption system.

PMID- 16623488
TI  - Theoretical study of the complex-forming CH + H2 --> CH2 + H reaction.
AB  - The complex-forming CH + H2 --> CH2 + H reaction is studied employing a recently
      developed global potential energy function. The reaction probability in the total
      angular momentum J = 0 limit is estimated with a four-atom quantum wave packet
      method and compared with classical trajectory and statistical theory results. The
      formation of complexes from different reactant internal states is also determined
      with wave packet calculations. While there is no barrier to reaction along the
      minimum energy path, we find that there are angular constraints to complex
      formation. Trajectory-based estimates of the low-pressure rate constants are made
      and compared with experimental results. We find that zero-point energy violation
      in the trajectories is a particularly severe problem for this reaction.

PMID- 16623489
TI  - Ab initio molecular dynamics with discrete variable representation basis sets:
      techniques and application to liquid water.
AB  - Finite temperature ab initio molecular dynamics (AIMD), in which forces are
      obtained from "on-the-fly" electronic structure calculations, is a widely used
      technique for studying structural and dynamical properties of chemically active
      systems. Recently, we introduced an AIMD scheme based on discrete variable
      representation (DVR) basis sets, which was shown to have improved convergence
      properties over the conventional plane wave (PW) basis set [Liu,Y.; et al. Phys.
      Rev. B 2003, 68, 125110]. In the present work, the numerical algorithms for the
      DVR based AIMD scheme (DVR/AIMD) are provided in detail, and the latest
      developments of the approach are presented. The accuracy and stability of the
      current implementation of the DVR/AIMD scheme are tested by performing a
      simulation of liquid water at ambient conditions. The structural information
      obtained from the present work is in good agreement with the result of recent
      AIMD simulations with a PW basis set (PW/AIMD). Advantages of using the DVR/AIMD
      scheme over the PW/AIMD method are discussed. In particular, it is shown that a
      DVR/AIMD simulation of liquid water in the complete basis set limit is possible
      with a relatively small number of grid points.

PMID- 16623490
TI  - Theory of diatomic molecules in an external electromagnetic field from first
      quantum mechanical principles.
AB  - We study a general problem of the translational/rotational/vibrational/electronic
      dynamics of a diatomic molecule exposed to an interaction with an arbitrary
      external electromagnetic field. The theory developed in this paper is relevant to
      a variety of specific applications, such as alignment or orientation of molecules
      by lasers, trapping of ultracold molecules in optical traps, molecular optics and
      interferometry, rovibrational spectroscopy of molecules in the presence of
      intense laser light, or generation of high order harmonics from molecules.
      Starting from the first quantum mechanical principles, we derive an appropriate
      molecular Hamiltonian suitable for description of the center of mass, rotational,
      vibrational, and electronic molecular motions driven by the field within the
      electric dipole approximation. Consequently, the concept of the Born-Oppenheimer
      separation between the electronic and the nuclear degrees of freedom in the
      presence of an electromagnetic field is introduced. Special cases of the dc/ac
      field limits are then discussed separately. Finally, we consider a perturbative
      regime of a weak dc/ac field, and obtain simple analytic formulas for the
      associated Born-Oppenheimer translational/rotational/vibrational molecular
      Hamiltonian.

PMID- 16623491
TI  - Theoretical investigation of the structure and coverage of the Si(111)-OCH3
      surface.
AB  - The surface structure, strain energy, and charge profile of the methoxylated
      Si(111) surface, Si(111)-OCH3, has been studied using quantum mechanics, and the
      results are compared to those obtained previously for Si(111)-CH3 and Si(111)
      C2H5. The calculations indicate that 100% coverage is feasible for Si(111)-OCH3
      (similar to the methylated surface), as compared to only approximately 80%
      coverage for the ethylated surface. These differences can be understood in terms
      of nearest-neighbor steric and electrostatic interactions. Enthalpy and free
      energy calculations indicate that the formation of the Si(111)-OCH3 surface from
      Si(111)-H and methanol is favorable at 300 K. The calculations have also
      indicated the conditions under which stacking faults can emerge on Si(111)-OCH3,
      and such conditions are contrasted with the behavior of Si(111)-CH3 and Si(111)
      CH2CH3 surfaces, for which stacking faults are calculated to be energetically
      feasible when etch pits with sufficiently long edges are present on the surface.

PMID- 16623492
TI  - On the nonequilibrium thermodynamics of large departures from Butler-Volmer
      behavior.
AB  - Large deviations from the behavior predicted by the Butler-Volmer equation of
      electrochemistry are accounted for using mesoscopic nonequilibrium
      thermodynamics. The nonequilibrium thermodynamic hypotheses are extended to
      include velocity space and cope with imperfect reactant transport leading to
      departures from Butler-Volmer behavior. This results in a modified Butler-Volmer
      equation in good agreement with experimental data. The distinct advantages of the
      method and its applicability to analyze other systems are briefly discussed.

PMID- 16623493
TI  - Conformational equilibrium of bis(trifluoromethanesulfonyl) imide anion of a room
      temperature ionic liquid: Raman spectroscopic study and DFT calculations.
AB  - The structure of bis(trifluoromethanesulfonyl) imide (TFSI-) in the liquid state
      has been studied by means of Raman spectroscopy and DFT calculations. Raman
      spectra of 1-ethyl-3-methylimidazolium (EMI+) TFSI- show relatively strong bands
      arising from TFSI- at about 398 and 407 cm(-1). Interestingly, the 407 cm(-1)
      band, relative to the 398 cm(-1) one, is appreciably intensified with raising
      temperature, suggesting that an equilibrium is established between TFSI-
      conformers in the liquid state. According to DFT calculations followed by normal
      frequency analyses, two conformers of C2 and C1 symmetry, respectively,
      constitute global and local minima, with an energy difference 2.2-3.3 kJ mol(-1).
      The wagging omega-SO2 vibration appears at 396 and 430 cm(-1) for the C1
      conformer and at 387 and 402 cm(-1) for the C2 one. Observed Raman spectra over
      the range 380-440 cm(-1) were deconvoluted to extract intrinsic bands of TFSI-
      conformers, and the enthalpy of conformational change from C2 to C1 was
      evaluated. The enthalpy value is in good agreement with that obtained by
      theoretical calculations. We thus conclude that a conformational equilibrium is
      established between the C1 and C2 conformers of TFSI- in the liquid EMI+TFSI-,
      and the C2 conformer is more favorable than the C1 one.

PMID- 16623494
TI  - 2H NMR evidence for the formation of random mesh phases in nonionic surfactant
      water systems.
AB  - Random mesh phases share many common features with the classical lamellar phase
      in that they are layered phases; but crucially, they possess nonuniform
      interfacial curvature, since the lamellae are pierced by water-filled pores. The
      introduction of curvature into the lamellae has been posited as a transitional
      precursor for other lyotropic phases. In this paper, we show that simple 2H
      nuclear magnetic resonance (NMR) experiments provide strong indication for the
      formation of the random mesh phase and the NMR data correlate well with
      literature results from small-angle X-ray scattering. The thermal evolution of
      the recorded quadrupolar splitting (DeltanuQ) is monitored within the lamellar
      phase of two nonionic surfactants, C16E6 and C12E5, as the samples are cooled or
      heated, and a marked and reversible change in the evolution of DeltanuQ is
      observed. Data from heavy water and deuterium labeled surfactant show the same
      temperature dependence and consequently report on the same structural changes
      with temperature. The formation of the random mesh phase is quantified in terms
      of an effective order parameter that is unity in the classical lamellar phase and
      takes values of <1 in the random mesh phase, reaching 0.6 at lower temperatures.

PMID- 16623496
TI  - Formation of a three-dimensional microstructure of Fe3O4-poly(vinyl alcohol)
      composite by evaporating the hydrosol under a magnetic field.
AB  - In this paper, we report on the self-assembly formation of three-dimensional
      microstructures of Fe3O4 hydrosol. First, we perform new, facile, and direct
      fabrication of a stable hydrosol of Fe3O4 nanoparticles, based on the sonolysis
      of an aqueous solution of iron acetate in the presence of PVA-100,000. This is
      then followed by investigations of the formation of different microstructures
      obtained on drying a drop of the water suspension on a glass microscope
      substrate. The evaporation was carried out both without and in the presence of an
      external magnetic field.

PMID- 16623495
TI  - Molecular conformations of protonated dipropylamine in AlPO4-11, AlPO4-31, SAPO
      34, and AlPO4-41 molecular sieves.
AB  - The host-guest interactions in AlPO4-11, AlPO4-31, SAPO-34, and AlPO4-41
      molecular sieves prepared using the same organic structure-directing agent, i.e.,
      dipropylamine, are investigated by a combination of Raman, 13C and 1H MAS NMR,
      and computer modeling studies. It was found that the organic molecules trapped
      within the pores of these four AlPO4-based materials exist as their protonated
      form and adopt distinct conformations in order to fit well with the pore
      structure of each host. In particular, the presence of two different types of
      conformations of protonated dipropylamine in the circular 12-ring channels of
      AlPO4-31 has been ascertained.

PMID- 16623497
TI  - X- (X = O, S) ions in alkali halide lattices through density functional
      calculations. 1. Substitutional defect models.
AB  - Monoatomic X- (X = O, S) chalcogen centers in MZ (M = Na, K, Rb and Z = Cl, Br,
      I) alkali halide lattices are investigated within the framework of density
      functional theory with the principal aim to establish defect models. In electron
      paramagnetic resonance (EPR) experiments, X- defects with tetragonal,
      orthorhombic, and monoclinic g-tensor symmetry have been observed. In this paper,
      models in which X- replaces a single halide ion, with a next nearest neighbor and
      a nearest neighbor halide vacancy, are validated for the X- centers with
      tetragonal and orthorhombic symmetry, respectively. As such defect models are
      extended, the ability to reproduce experimental data is a stringent test for
      various computational approaches. Cluster in vacuo and embedded cluster schemes
      are used to calculate energy and EPR parameters for the two vacancy
      configurations. The final assignment of a defect structure is based on the
      qualitative and quantitative reproduction of experimental g and (super)hyperfine
      tensors.

PMID- 16623498
TI  - X- (X = O, S, Se) Ions in alkali halide lattices through density functional
      calculations. 2. Interstitial defect models.
AB  - Density functional theory techniques are used to investigate the defect structure
      of X- (X = O, S, Se) ions in MZ (M = Na, K, Rb and Z = Cl, Br) alkali halides
      which exhibit monoclinic-I g-tensor symmetry, using cluster in vacuo, embedded
      cluster, and periodic embedding schemes. Although a perturbed interstitial defect
      model was suggested from electron paramagnetic resonance experiments (EPR), the
      nature of the perturbation is still unknown. An appropriate defect model is
      developed theoretically by comparing structural and energetical properties of
      various defect configurations. Further validation is achieved by cross
      referencing experimental and computed EPR data. On the basis of the computational
      results, the following defect model is proposed: the X- ion is located
      interstitially with a charge compensating halide vacancy in its first
      coordination shell.

PMID- 16623499
TI  - Low-temperature anomalies of two-photon absorption in In2O3 nanocrystals
      incorporated into PMMA matrixes.
AB  - By using a method of two-photon absorption, it has been observed that
      monodisperse In2O3 nanocrystals (NCs) with sizes equal to approximately 14-24 nm
      show significant increase of two-photon absorption at low temperatures. When T =
      40 K, the two-photon absorption coefficients for low-sized samples drastically
      increase, whereas such enhancement for the samples with averaged sizes above
      approximately 24 nm is not significant. The nondiagonal tensor components give
      one-order-less two-photon absorption values. A principal role in the observed
      dependences is played by interface nanolayers, demonstrating substantial
      contribution of nanoconfined effects. This phenomenon could only be observed in
      highly monodisperse NCs. Increase of the size distribution substantially
      suppresses the two-photon absorption observed. For the relatively large
      nanocrystals, the effects are comparable with those of the bulklike crystals. At
      the same time, the drastic increase at low temperatures may indicate a
      substantial role of the phonon subsystem.

PMID- 16623500
TI  - Radical ions of alpha,alpha'-bis(diphenylamino)-capped oligothiophenes: a
      combined spectroelectrochemical and theoretical study.
AB  - A new homologous series of alpha,alpha'-bis(diphenylamino)-capped
      oligothiophenes, prepared by a palladium-catalyzed coupling reaction of
      stannylated 2-diphenylaminothiophenes with 2-mono- or 2,5-dibromothiophenes and
      their homologues, was studied by in situ ESR/UV-vis/NIR spectroelectrochemistry.
      In general, the oxidation potentials of these oligothiophenes were found to be
      proportional to the inverse number of thiophene units. However, the potential
      slope of the first oxidation is completely different from that of higher
      oxidation steps. Trication radicals were identified by electron spin resonance
      (ESR) for higher thiophene homologues in addition to monocation radicals
      (polarons). According to the ESR hyperfine structures, the unpaired electron is
      delocalized in the conjugated system. In contrast to the parent alpha,alpha'
      bis(diphenylamino)-capped oligothiophenes, the UV-vis/NIR absorption maxima of
      the oxidized species strongly depend on the number of thiophene units. Spin
      restricted and spin-unrestricted Kohn-Sham density functional calculations were
      used to explain and to understand these properties. Absorption wavelength and
      intensities were calculated by the time-dependent density functional response
      theory. Unrestricted density functional calculations of oligothiophene dications
      (bipolarons) with five or more thiophene rings result in spin-broken structures
      which may be considered as two-polaron biradicals (polaron pairs).

PMID- 16623501
TI  - Thermodynamic calculations in the system CH4-H2O and methane hydrate phase
      equilibria.
AB  - Using the Gibbs function of reaction, equilibrium pressure, temperature
      conditions for the formation of methane clathrate hydrate have been calculated
      from the thermodynamic properties of phases in the system CH4-H2O. The
      thermodynamic model accurately reproduces the published phase-equilibria data to
      within +/-2 K of the observed equilibrium boundaries in the range 0.08-117 MPa
      and 190-307 K. The model also provides an estimate of the third-law entropy of
      methane hydrate at 273.15 K, 0.1 MPa of 56.2 J mol(-1) K(-1) for 1/nCH4.H2O,
      where n is the hydrate number. Agreement between the calculated and published
      phase-equilibria data is optimized when the hydrate composition is fixed and
      independent of the pressure and temperature for the conditions modeled.

PMID- 16623502
TI  - Investigations of the adsorption of n-pentane in several representative zeolites.
AB  - We have examined the adsorption of n-pentane in several representative zeolites
      such as silicalite (MFI), ferrierite (FER), zeolite L (LTL), and faujasite
      zeolites with FAU structure including siliceous Y (Si-Y) and Na-Y by using FT
      Raman spectroscopy in combination with thermogravimetric analysis (TGA) with
      particular attention being paid to the conformational and dynamic behavior of the
      guest molecule. The results indicate that the framework topology mainly dictates
      the conformation of n-pentane in a zeolite. For the zeolites with channel systems
      such as silicalite, ferrierite, and zeolite L, the population of the all-trans
      conformer increases upon loading, given that the geometry of the isomer fits
      better in the channel. When n-pentane is adsorbed in zeolites with a large
      cavity, such as Si-Y and Na-Y, the distribution of the all-trans (TT) and trans
      gauche (TG) conformers is similar to that of pure liquid, suggesting that the
      large supercage in the framework imposes minimal effect on the conformational
      equilibrium. The dynamics of the guest molecule is, however, influenced
      significantly by the existence of cations. Adsorption of n-pentane in a siliceous
      framework such as silicalite and Si-Y results in extensive molecular motion at
      room temperature, the degree of which decreases with decreasing temperature. In
      zeolites ferrierite, L, and Na-Y, the presence of cations in the framework
      markedly hinders the overall molecular motion. The cations clearly play a role in
      the observed static disorder of the guest molecule in zeolite L. Important
      information regarding the location of the n-pentane molecules within silicalite
      and ferrierite is also obtained.

PMID- 16623503
TI  - Rapid growth and flow-mediated nucleation of millimeter-scale aligned carbon
      nanotube structures from a thin-film catalyst.
AB  - We discuss the rapid growth of films and lithographically templated
      microstructures of vertically aligned small-diameter multiwalled carbon nanotubes
      (VA-MWNTs), by atmospheric-pressure thermal chemical vapor deposition (CVD) of
      C2H4/H2/Ar on a Fe/Al2O3 catalyst film deposited by electron beam evaporation.
      The structures grow to 1 mm height in 15 min and reach close to 2 mm in 60 min.
      The growth rate and final height of CNT microstructures grown from catalyst
      patterns depend strongly on the local areal density of catalyst, representing a
      reverse analogue of loading effects which occur in plasma etching processes.
      Abrupt transitions between areas of micrometer-thick tangled CNT films and
      millimeter-scale aligned CNT structures are manipulated by changing the duration
      of pretreatment by H2/Ar prior to introduction of C2H4 and by changing the
      configuration of the substrate sample in the furnace tube. This demonstrates that
      the flow profile over the sample mediates the supply of reactants to the catalyst
      and that pretreatment using H2 significantly affects the initial activity of the
      catalyst.

PMID- 16623504
TI  - First-principles calculations of migration energy of lithium ions in halides and
      chalcogenides.
AB  - Migration of Li+ ions via the vacancy mechanism in LiX (X = F, Cl, Br, and I)
      with the rocksalt and hypothetical zinc blende structures and Li2X (X = O, S, Se,
      and Te) with the antifluorite structure has been investigated using first
      principles projector augmented wave calculations with the generalized gradient
      approximation. The migration paths and energies, determined by the nudged-elastic
      band method, are discussed on the basis of two idealized models: the rigid-sphere
      and charged-sphere models. The trajectories and energy profiles of the migration
      in these lithium compounds vary between these two models, depending on the anion
      species and crystal structure. The migration energies in LiX with both the
      rocksalt and hypothetical zinc blende structures show a tendency to decrease with
      increasing periodic number of the anion species in the periodic table. This is
      consistent with the widely accepted view that anion species with large ionic
      radii and high polarizabilities are favorable for good ionic conduction. In
      contrast, Li2O exhibits the lowest migration energy among Li2X compounds,
      although O is the smallest among the chalcogens, indicating that electrostatic
      attractive interactions play the dominant role in the inter-ion interactions in
      Li2O and, therefore, in the ion migration.

PMID- 16623505
TI  - Synthesis and characterizations of amorphous carbon nanotubes by pyrolysis of
      ferrocene confined within AAM templates.
AB  - Amorphous carbon nanotubes (a-CNTs) are synthesized by pyrolysis of ferrocene
      confined in the nanopores of the anodic alumina membrane (AAM) and characterized
      by field emission scanning electron microscopy (SEM), energy-dispersive X-ray
      spectroscopy (EDS), transmission electron microscopy (TEM), electron energy-loss
      spectroscopy (EELS), and Raman spectroscopy. It is shown that the a-CNT has an
      ultrathin amorphous wall (approximately 3 nm) and a relatively large diameter
      (approximately 50 nm), and is capsulated with iron oxide nanoparticles. It is
      found that the growth of the a-CNTs is governed mainly by the template limitation
      effect. Electrical transport measurements on individual a-CNTs demonstrate that
      the a-CNT may be connected with electrodes via either ohmic or Schottky contacts,
      and the resisitivity of the a-CNTs was measured to be 4.5 x 10(-3) Omega cm.

PMID- 16623506
TI  - Dielectric study of the slow motional processes in the polymorphic States of
      anhydrous caffeine.
AB  - Molecular mobility in crystalline anhydrous caffeine was studied by the
      dielectric technique of thermally stimulated depolarization currents (TSDC). Two
      relaxational processes were found, one appearing at approximately -10 degrees C
      that is ascribed to a reorientational glass transition, and a higher temperature
      one that probably arises from local molecular motions that are precursors of
      diffusion and sublimation. The experimental results suggest that both crystalline
      phases II and I of caffeine, that have distinct crystal structures, are solid
      rotator phases. Furthermore, this dynamic reorientational disorder shows a
      reorientational glass transition at the same temperature in phase II and in
      metastable phase I.

PMID- 16623507
TI  - Electrical bistability and memory phenomenon in carbon nanotube-conjugated
      polymer matrixes.
AB  - We have observed electrical bistability and large conductance switching in
      functionalized carbon nanotube (CNT)-conjugated polymer composites at room
      temperature. The concentration of the CNTs in the polymer matrix controlled the
      degree of bistability. Conduction mechanism applicable in each of the conducting
      states has been identified. The switching had an associated memory phenomenon and
      was reversible in nature. In the bistable devices, the active layer retained its
      high-conducting state until a reverse voltage erased it. We could "write" or
      "erase" a state and "read" it for many cycles for random-access memory
      applications.

PMID- 16623508
TI  - Triplet-state and singlet oxygen formation in fluorene-based alternating
      copolymers.
AB  - Data are reported on the triplet states of a series of fluorene-based A-alt-B
      type alternating copolymers based on pulse radiolysis-energy transfer and flash
      photolysis experiments. From the pulse radiolysis experiments, spectra are given
      for eight copolymers involving phenylene, thiophene, benzothiadiazole, and
      oligothienylenevinylene groups. Quantum yields for triplet-state formation (PhiT)
      have been obtained by flash photolysis following laser excitation and in one case
      by photoacoustic calorimetry. In addition, yields of sensitized formation of
      singlet oxygen have been determined by time-resolved phosphorescence and are, in
      general, in excellent agreement with the PhiT values. In all cases, the presence
      of thiophene units is seen to increase intersystem-crossing quantum yields,
      probably because of the presence of the heavy sulfur atom. However, with the
      poly[2,7-(9,9-bis(2'-ethylhexyl)fluorene)-alt-1,4-phenylene] (PFP), thiophene S,S
      dioxide (PFTSO2) and benzothiadiazole (F8BT) copolymers, low yields of triplet
      formation are observed. With three of the copolymers, the energies of the triplet
      states have been determined. With PFP, the triplet energy is virtually identical
      to that of poly[2,7-(9,9-bis(2'-ethylhexyl)fluorene)]. In contrast, with fluorene
      thiophene copolymers PFaT and PF3T, the triplet energies are closer to those of
      thiophene oligomers, indicating that there is significant conjugation between
      fluorene and thiophene units but also that there is a more localized triplet
      state than with the homopolymers.

PMID- 16623509
TI  - Metastable gamma-MnS hierarchical architectures: synthesis, characterization, and
      growth mechanism.
AB  - Preparation of shape-controlled metastable gamma-MnS semiconductor nanocrystals
      has been achieved on a large scale through a simple solvothermal method in the
      presence of PVP. The key strategy is the use of sulfur powder as sulfur source in
      ethylene glycol (EG) solvent that also acted as a weak reducing agent. Reaction
      parameters such as reaction time and temperature are found to be important in
      controlling various hierarchical architectures, such as homogeneous semi-hollow
      core-shell, hollow nanospheres, and nanowires. Transmission electron microscopy
      observations indicate that these hierarchical architectures are formed mainly via
      Ostwald ripening. The optical absorption measurements reveal that these novel
      architectures exhibit remarkable shift of absorption peak during the course of
      structural compaction and grain growth.

PMID- 16623510
TI  - From fractal to nanorod porphyrin J-aggregates. Concentration-induced tuning of
      the aggregate size.
AB  - A structural change from fractal to nanorod J-aggregates of tetrakis(4
      sulfonatophenyl)porphyrin has been obtained by acting on the intermolecular
      interaction potential. The size and shape of these self-assembled porphyrin
      clusters have been monitored under different experimental conditions, by means of
      polarized and depolarized dynamic light scattering and small and wide angle
      elastic light scattering. At sufficiently low porphyrin concentration and high
      ionic strength, the shielded repulsive potential seems to be responsible for the
      fractal structure of the aggregates. On the contrary, at low ionic strength
      (nonshielded potential) and high porphyrin concentration, these species self
      assemble in a rodlike arrangement. The length of the so-formed rod-shaped
      aggregates decreases on increasing porphyrin concentration. Moreover, both
      fractals and rods display a structure-dependent optical activity induced by a
      chiral template.

PMID- 16623511
TI  - Silica nanocoils.
AB  - We report here the results of nanoparticle-catalyzed synthesis of a variety of
      silica nanocoils (SiNCs) under similar growth conditions to those of making
      regular straight silica/silicon nanowires (SiNWs). Synthesis of individual SiNCs
      with alternating coiled and straight segments was achieved with cobalt
      nanoparticle catalysts at alternating temperatures. In addition, a variety of
      SiNCs, including multiple SiNCs sharing the same nanoparticle catalyst, SiNC
      double helices, and individual SiNCs with varying pitches and diameters were
      made.

PMID- 16623512
TI  - Microwave-assisted synthesis of calcium carbonate (vaterite) of various
      morphologies in water-ethylene glycol mixed solvents.
AB  - A fast microwave-assisted method is reported for the synthesis of CaCO3
      (vaterite) with various morphologies in the water/ethylene glycol (EG) system
      with surfactants. Our experiments show that microwave heating, reaction time,
      surfactant, and the water-EG mixed solvents play important roles in the
      morphology of vaterite. Vaterite with dagger-like, bicone-like, shuttle-like
      morphology and microspheres self-assembled from nanoparticles have been obtained
      by adjusting the experimental parameters. The products were characterized by X
      ray powder diffraction, transmission electron microscopy, and scanning electron
      microscopy.

PMID- 16623513
TI  - Surface plasmon-quantum dot coupling from arrays of nanoholes.
AB  - The coupling of semiconductor quantum dots (QDs) to the surface plasmon (SP)
      modes of nanohole arrays in a metal film was demonstrated for the first time,
      showing enhancement in the spontaneous emission by 2 orders of magnitude. The SP
      enhanced transmission resonances of the nanohole arrays were tuned around the
      photoluminescence (PL) peak of polystyrene-b-poly(acrylic acid) (PS-b-PAA)
      stabilized cadmium sulfide (CdS) quantum dots (QDs) in contact with the arrays.
      As a result the overall PL from the SP-QD system was enhanced by 2 orders of
      magnitude, even after excluding the enhanced transmission of the nanohole array
      without the QDs. The maximum enhancement occurred when the resonance from the
      nanohole array matched the QD PL spectrum. Time-resolved PL measurements were
      used to estimate the relative contribution of different physical mechanisms to
      the enhanced spontaneous emission. The increased spontaneous emission in the SP
      QD system is promising for prospective plasmonic light-emitting devices
      incorporating QDs.

PMID- 16623514
TI  - Aluminum chloride as a solid is not a strong Lewis acid.
AB  - Aluminum chloride is used extensively as Lewis acid catalyst in a variety of
      industrial processes, including Friedel-Crafts and Cl/F exchange reactions. There
      is a common misconception that pure AlCl3 is itself a Lewis acid. In the current
      study, we use experimental and computational methods to investigate the surface
      structure and catalytic properties of solid AlCl3. The catalytic activity of
      AlCl3 for two halide isomerization reactions is studied and compared with
      different AlF3 phases. It is shown that pure solid AlCl3 does not catalyze these
      reactions. The (001) surface of crystalline AlCl(3) is the natural cleavage plane
      and its structure is predicted via first principles calculations. The chlorine
      ions in the outermost layer of the material mask the Al3+ ions from the external
      gas phase. Hence, the experimentally found catalytic properties of pure solid
      AlCl3 are supported by the predicted surface structure of AlCl3.

PMID- 16623515
TI  - Conformational analysis of sulfate species on Ag/Al2O3 by means of theoretical
      and experimental vibration spectra.
AB  - The formation and configuration of sulfate species on Ag/Al2O3 were studied by
      means of in situ diffuse reflectance infrared Fourier transform spectroscopy
      (DRIFTS) and density functional theory (DFT) calculations. The comparison between
      theoretical and experimental vibration spectra enable us to draw the following
      conclusions: Bidentate sulfate species rather than tridentate sulfate species are
      the predominant surface species on Ag/Al2O3. Moreover, both bidentate and
      tridentate sulfate species may coexist on the catalyst surface at a lower
      coverage. The accumulation of surface sulfate species could well explain the blue
      shift of the sulfate species in IR spectra. In addition, the in situ DRIFTS could
      distinguish between the sulfate species that linked to Al site and Ag site, which
      was well supported by temperature-programmed desorption (TPD) results.

PMID- 16623516
TI  - Hydrogen storage properties of metal nitroprussides M[Fe(CN)5NO], (M = Co, Ni).
AB  - The volumetric hydrogen adsorption isotherms of two isostructural dehydrated
      cubic metal nitroprussides M[Fe(CN)5NO] (M = Co2+, Ni2+) have been measured up to
      a pressure of 760 Torr at 77 and 87 K. These materials are among the most
      efficient H2 sorbents based on porous coordination polymers reported to date. The
      H2 uptake in both materials is approximately 1.6 wt % at 77 K and 760 torr. These
      H2 capacities match those reported recently in the structurally related
      M3[Co(CN)6]2 compounds and are approximately 25% higher than those reported for
      Zn4O(1,4-benzenedicarboxylate)3 under the same conditions of temperature and
      pressure. The isosteric heats of H2 adsorption calculated from the 77 and 87 K
      isotherms for both materials were found to vary from approximately 7.5 kJ/mol at
      0.40 wt % coverage to approximately 5.5 kJ/mol at 1.2 wt % coverage. The N2 BET
      surface areas were determined to be 634 m2/g and 523 m2/g for M = Ni and M = Co,
      respectively.

PMID- 16623517
TI  - Molecular depth profiling with cluster ion beams.
AB  - Peptide-doped trehalose thin films have been characterized by bombardment with
      energetic cluster ion beams of C60+ and Aux+ (x = 1, 2, 3). The aim of these
      studies is to acquire information about the molecular sputtering process of the
      peptide and trehalose by measurement of secondary ion mass spectra during
      erosion. This system is important since uniform thin films of approximately 300
      nm thickness can be reproducibly prepared on a Si substrate, allowing detailed
      characterization of the resulting depth profile with different projectiles. The
      basic form of the molecular ion intensity as a function of ion dose is described
      by a simple analytical model. The model includes parameters such as the molecular
      sputtering yield, the damage cross section of the trehalose or the peptide, and
      the thickness of a surface layer altered by the projectile. The results show that
      favorable conditions for successful molecular depth profiling are achieved when
      the total sputtering yield is high and the altered layer thickness is low.
      Successful molecular depth profiles are achieved with all of the cluster
      projectiles, although the degree of chemical damage accumulation was slightly
      lower with C60. With C60 bombardment, the altered layer thickness of about 20 nm
      and the damage cross section of about 5 nm2 are physically consistent with
      predictions of molecular dynamics calculations available for similar chemical
      systems. In general, the model presented should provide guidance in optimizing
      experimental parameters for maximizing the information content of molecular depth
      profiling experiments with complex molecular thin film substrates.

PMID- 16623518
TI  - Initial surface reactions of TiO2 atomic layer deposition onto SiO2 surfaces:
      density functional theory calculations.
AB  - We present a density functional theory (DFT) study of the initial surface
      reactions of TiO2 deposition onto a SiO2 substrate using atomic layer deposition
      (ALD). The precursors for the deposition process were chosen to be TiCl4 and H2O,
      and several cluster models were used for the SiO2 substrate. We predict the
      activation barriers, transition states, and reaction pathways of the surface
      reactions, and we investigate the effect of surface heterogeneity (such as the
      presence of siloxane bridges) on the reactivity of the SiO2 surface. Our study
      suggests that the concentration and arrangement of different reactive groups on
      the substrate will strongly dictate the process of film growth during ALD,
      including the film morphology and the growth rate.

PMID- 16623519
TI  - Evidence of the interaction of evaporated Pt nanoparticles with variously treated
      surfaces of highly oriented pyrolytic graphite.
AB  - The interactions of Pt nanoparticles, deposited by evaporation onto highly
      oriented pyrolytic graphite surfaces modified by kiloelectronvolt Ar+ beam
      treatment, have been studied by X-ray photoelectron spectroscopy core-level line
      shape analysis. The C1s and Pt4f7/2 peaks were each considered to be composed of
      one asymmetric peak, and changes in their asymmetry parameters were used to study
      their interfacial interactions. In addition to these changes, strong signal
      intensity changes with time were found for both the C1s and Pt4f peaks,
      indicating an initial crystalline orientational instability of the Pt
      nanoparticles, which is supported by time-dependent high-resolution electron
      microscopy studies at elevated temperatures.

PMID- 16623520
TI  - Ab initio molecular dynamics simulation of NO reactivity on the CaO(001) surface.
AB  - Ab initio molecular dynamics (MD) is used to investigate NO reaction processes on
      the (001) surface of CaO. A novel path is proposed for the first steps of
      nitrogen oxides reactivity catalyzed by the CaO surface. The mechanism consists
      of the formation of anionic dimers, adsorbing on the surface cations, at the
      expense of oxidized NO species adsorbed on surface anions. The complete charge
      transfer process takes place in two steps, producing first monovalent anionic
      dimers (NO)2- and, later on, divalent anionic dimers (NO)2(2-). These redox
      processes cause spin quenching and are observed in the short time scale of the ab
      initio MD simulation at 300 K. The results presented provide a rationalization of
      a recent electron spin resonance (ESR) investigation indicating that the
      spectroscopy is silent to most of the nitrogen oxide species adsorbed on CaO
      powders, despite deposition of paramagnetic NO molecules at room temperature.

PMID- 16623521
TI  - Quantum chemical study of mechanisms for oxidative dehydrogenation of propane on
      vanadium oxide.
AB  - We have carried out a hybrid density functional study of mechanisms for oxidative
      dehydrogenation of propane on the (010) surface of V2O5. The surface was modeled
      using both vanadium oxide clusters and a periodic slab. We have investigated a
      Mars-van Krevelen mechanism that involves stepwise adsorption of the propane at
      an oxygen site followed by desorption of a water molecule and propene, and
      subsequent adsorption of an oxygen molecule to complete the catalytic cycle. The
      potential energy surface is found to have large barriers, which are lowered
      somewhat when the possibility of a triplet state is considered. The barriers for
      propane adsorption and propene elimination are 45-60 kcal/mol. The highest energy
      on the potential energy surface at the B3LYP/6-31G* level of theory is about 80
      kcal/mol above the energy of the reactants and corresponds to formation of an
      oxygen vacancy after water elimination. Subsequent addition of an oxygen molecule
      to fill the vacancy is predicted to be energetically downhill. The reactions of
      propane at a bridging oxygen site and at a vanadyl site have similar energetics.
      The key results of the cluster calculations are confirmed by periodic
      calculations. Factors that may lower the barriers on the potential energy
      surface, including the interaction of vanadium oxide clusters with a support
      material and a concerted reaction with O2, are discussed.

PMID- 16623522
TI  - Observation of pH-dependent back-electron-transfer dynamics in alizarin/TiO2
      adsorbates: importance of trap states.
AB  - The dependence of the interfacial electron transfer in alizarin-sensitized TiO2
      nanoparticles on the sample pH has been examined via transient absorbance
      spectroscopy in the visible spectral region (443-763 nm). Excitation of the
      alizarin/TiO2 system with visible pump pulses (lambdaexc = 500 nm) leads to a
      very fast electron injection (tauinj < 100 fs) over a wide pH range. Back
      electron transfer shows complicated multiphasic kinetics and strongly depends on
      the acidity of the solution. The strong dependence of back-electron-transfer
      dynamics on the ambient pH value is explained by a Nernstian-type change in the
      semiconductor band energy. Indeed, a variation of pH values over 7 units leads to
      a approximately 0.42 eV change of the conduction band edge position (i.e., the
      nominal free energy of the electron in the electrode). Assuming a pH-independent
      redox potential of the dye, this change was sufficient to push the system to a
      condition where direct photoinitiated electron injection to intraband gap surface
      states could be investigated. The existence of an electron-transfer pathway via
      surface trap states is supported by the similarity of the observed back-electron
      transfer kinetics of alizarin/TiO2 at pH 9 and alizarin/ZrO2 reported in earlier
      work (J. Phys. Chem. B 2000, 104, 8995), where the conduction band edge is
      approximately 1 eV above the excited state of the dye. The influence of surface
      trap states on interfacial electron transfer has been studied, and a detailed
      analysis of their population, depopulation, and relaxation kinetics is performed.
      Therefore, alizarin adsorbed on the surface of TiO2 nanoparticles is an ideally
      suited system, where pH-dependent investigations allow a detailed study of the
      electron dynamics in trap states of TiO2 nanoparticles.

PMID- 16623523
TI  - Effects of thermal treatments on the recovery of adsorbed water and
      photocatalytic activities of TiO2 photocatalytic systems.
AB  - The effects of thermal treatments on the rehydration process and photocatalytic
      activity were investigated by 1H NMR spectroscopy for six anatase abundant TiO2
      photocatalysts with different properties. Acetic acid and benzoic acid were
      employed for photodecomposition in aqueous suspension. After the calcinations at
      973 K, physisorbed water layers recovered relatively fast for P25, F4, and AMT
      600 (shorter than 24 h) with no significant enhancement of the photocatalytic
      decomposition. On the other hand, for ST-01, UV-100, and AMT-100, the recovery
      was very slow (longer than 1 week) and only partially reversible, and the
      photocatalytic decomposition was considerably enhanced but retarded with
      rehydration. In the presence of adsorbed water, the binding of a carboxyl group
      of the molecules with adsorbed water is considered to compete with the direct
      adsorption on the surface, which reduces the amount of the direct adsorption and
      results in the reduction in the photocatalytic efficiency. In addition, the
      photocatalytic decomposition of benzoic acid with an aromatic ring was much
      faster in all of the TiO2 aqueous suspensions and more enhanced for the fully
      dehydroxylated TiO2 than that of acetic acid. These results suggest that the most
      efficient photocatalytic sites should be the hydrophobic sites on the TiO2
      surface. The difference among the rehydration rates of different TiO2 is
      discussed in terms of thermally induced changes of surface morphology.

PMID- 16623524
TI  - Derivation of force field parameters for SnO2-H2O surface systems from plane-wave
      density functional theory calculations.
AB  - Plane-wave density functional theory (DFT-PW) calculations were performed on bulk
      SnO2 (cassiterite) and the (100), (110), (001), and (101) surfaces with and
      without H2O present. A classical interatomic force field has been developed to
      describe bulk SnO2 and SnO2-H2O surface interactions. Periodic density functional
      theory calculations using the program VASP (Kresse et al., 1996) and molecular
      cluster calculations using Gaussian 03 (Frisch et al., 2003) were used to derive
      the parametrization of the force field. The program GULP (Gale, 1997) was used to
      optimize parameters to reproduce experimental and ab initio results. The
      experimental crystal structure and elastic constants of SnO2 are reproduced
      reasonably well with the force field. Furthermore, surface atom relaxations and
      structures of adsorbed H2O molecules agree well between the ab initio and force
      field predictions. H2O addition above that required to form a monolayer results
      in consistent structures between the DFT-PW and classical force field results as
      well.

PMID- 16623525
TI  - Molecular dynamics simulation study of water adsorption on hydroxylated graphite
      surfaces.
AB  - In this paper, we present results from molecular dynamic simulations devoted to
      the characterization of the interaction between water molecules and hydroxylated
      graphite surfaces considered as models for surfaces of soot emitted by aircraft.
      The hydroxylated graphite surfaces are modeled by anchoring several OH groups on
      an infinite graphite plane. The molecular dynamics simulations are based on a
      classical potential issued from quantum chemical calculations. They are performed
      at three temperatures (100, 200, and 250 K) to provide a view of the structure
      and dynamics of water clusters on the model soot surface. These simulations show
      that the water-OH sites interaction is quite weak compared to the water-water
      interaction. This leads to the clustering of the water molecules above the
      surface, and the corresponding water aggregate can only be trapped by the OH
      sites when the temperature is sufficiently low, or when the density of OH sites
      is sufficiently high.

PMID- 16623526
TI  - Coverage-dependent kinetics and thermodynamics of carbon monoxide adsorption on a
      ternary copper catalyst derived from static adsorption microcalorimetry.
AB  - A reliable method for adsorption systems in equilibrium is established to derive
      coverage-dependent kinetics and thermodynamics from the volumetric data obtained
      during the static microcalorimetric measurement of heats of adsorption. The
      Wigner-Polanyi equation is applied to analyze the pressure change as a function
      of time during stepwise dosing of the adsorptive until thermodynamic adsorption
      desorption equilibrium is established. For carbon monoxide adsorption on a
      hydrogen-reduced Cu/ZnO/Al2O3 catalyst, the adsorption rate constant (ka) is
      found to be in the range from 10(-6) to 10(-4) Pa(-1) s(-1), and the desorption
      rate constant (kd) from 10(-4) to 10(-2) s(-1), both increasing with fractional
      coverage theta. The kinetically derived equilibrium constant Ktheta is in good
      agreement with Ktheta obtained from the adsorption isotherm. RT ln(Kp0) and the
      differential heat of adsorption (qdiff) were found to decrease in parallel,
      reflecting a normal Temkin-type heterogeneity.

PMID- 16623527
TI  - Kinetic pathways of phase ordering in lipid raft model systems.
AB  - We studied kinetic pathways of order-order transitions in bilayer lipid mixtures
      using a time-dependent Ginzburg-Landau (TDGL) approach. During the stripe-to
      hexagonal phase transition in an incompressible two-component system, the stripe
      phase first develops a pearl-like instability along the phase boundaries, which
      grows and drives the stripes to break up into droplets that arrange into a
      hexagonal pattern. These dynamic features are consistent with recent experimental
      observations. During the disorder-to-hexagonal phase transition in an
      incompressible three-component system, the disordered state first passes through
      a transient stripelike structure, which eventually breaks up into a hexagonal
      droplet phase. Our results suggest experiments with synthetic vesicles where the
      stripelike patterns could be observed.

PMID- 16623528
TI  - Effect of ionic solutes on the hydrogen bond network dynamics of water: power
      spectral analysis of aqueous NaCl solutions.
AB  - To understand the modifications of the hydrogen bond network of water by ionic
      solutes, power spectra as well as static distributions of the potential energies
      of tagged solvent molecules and solute ions have been computed from molecular
      dynamics simulations of aqueous NaCl solutions. The key power spectral features
      of interest are the presence of high-frequency peaks due to localized vibrational
      modes, the existence of a multiple time scale or 1/falpha frequency regime
      characteristic of networked liquids, and the frequency of crossover from 1/falpha
      type behavior to white noise. Hydrophilic solutes, such as the sodium cation and
      the chloride anion, are shown to mirror the multiple time scale behavior of the
      hydrogen bond network fluctuations, unlike hydrophobic solutes which display
      essentially white noise spectra. While the power spectra associated with tagged
      H2O molecules are not very sensitive to concentration in the intermediate
      frequency 1/falpha regime, the crossover to white noise is shifted to lower
      frequencies on going from pure solvent to aqueous alkali halide solutions. This
      suggests that new and relatively slow time scales enter the picture, possibly
      associated with processes such as migration of water molecules from the hydration
      shell to the bulk or conversion of contact ion pairs into solvent-separated ion
      pairs which translate into variations in equilibrium transport properties of salt
      solutions with concentration. For anions, cations, and solvent molecules, the
      trends in the alpha exponents of the multiple time scale region and the self
      diffusivities are found to be strongly correlated.

PMID- 16623530
TI  - Modeling of supramolecular ordering and physicochemical properties in cyclohexane
      ethanol mixtures.
AB  - The quasichemical model of the nonideal associated solution (QCNAS) was used to
      analyze the excess thermodynamic functions and permittivity of cyclohexane
      ethanol mixtures in the entire range of compositions and in a wide temperature
      range. A new model of supramolecular organization was substantiated, taking into
      account chain and cyclic aggregation of alcohol with the formation of chain
      aggregates of arbitrary size, which describes a set of physicochemical properties
      of this mixture with complicated behavior of both thermodynamic and dielectric
      properties. Equilibrium constants and thermodynamic parameters of H bonding
      having cooperative character and integral and differential characteristics of
      aggregation and the structural parameters of aggregates were determined. It was
      established that the role of nonpolar cyclic structures increases as alcohol
      concentration decreases. The model describes the permittivity of solutions in the
      entire range of compositions and reproduces a minimum of the dipolar correlation
      factor in the range of dilute alcohol solutions. The new data obtained on the
      supramolecular ordering characterized by the long-range molecular correlations
      due to H bonding are discussed in detail.

PMID- 16623529
TI  - Gibbs energies of transfer of alkali metal cations between mutually saturated
      water-solvent systems determined from extraction experiments with radiotracer
      137Cs.
AB  - Thermodynamic standard Gibbs energies of transfer of alkali metal cations related
      to Cs+ cation [DeltatG degrees*,(Cs+)-[DeltatG degrees*,(M+)] between several
      mutually saturated solvents of the type water-solvent were calculated from
      determined extraction exchange constants Kexch degrees,*(Cs+/M+). The used liquid
      liquid extraction method with radioactive tracing by 137Cs permits attaining
      higher precision of the values as compared to the methods used up to now. The
      data for o-nitrophenyloctyl ether, 1,2-dichloroethane, and 1-octanol were
      compared with literature sources and recommended absolute values of DeltatG
      degrees,*M+) are reported. For dissociating solvents, the dependences of [DeltatG
      degrees,*(Cs+) - [DeltatG degrees,*(M+)] on Gibbs energy of hydration of an ion,
      DeltaGhydr degrees are straight lines either for four cations Cs+, Rb+, K+, and
      Na+ (nitrosolvents) or for three cations Cs+, Rb+, and K+ (1,2-dichloroethane and
      1-octanol). The hydration of Na+ and still more of Li+ in the water-saturated
      organic phase is apparent from the results. This manifests for high-water-content
      equilibrium 1-octanol even in a reversal of the values [i.e., DeltatG
      degrees*,(Li+) being more negative than DeltatG degrees,*(Na+)], although for
      Cs+, Rb+, and K+, the general trend is conserved. Water-saturated 1-octanol is
      thus slightly less basic than water, but the overall selectivity is very low. For
      one studied nondissociating solvent, dioctyl sebacate, the trend of the
      dependences of log Kexch degrees,*(CsB/M+) on DeltaGhydr degrees is similar to
      that of Kexch degrees,*(Cs+/M+) for polar solvents, but different for different
      anions B, thus reflecting ion association in the organic phase.

PMID- 16623531
TI  - Ab initio theoretical study of temperature and density dependence of molecular
      and thermodynamic properties of water in the entire fluid region: autoionization
      processes.
AB  - The temperature and density dependence of the molecular and thermodynamic
      properties of water is investigated theoretically by means of the ab initio
      electronic structure theory combined with the reference interaction site model
      method, so-called RISM-SCF. We consider the autoionization process (H2O + H2O
      right harpoon over left harpoon H3O+ + OH-) by regarding H2O, H3O+, and OH- as
      "solute" molecules in an aqueous solution and evaluate molecular geometry,
      electronic structure, solvation structure, and the ionic product of water (pKw)
      of these species as functions of thermodynamic conditions. In our previous paper,
      we calculated these properties by using essentially the same method in a wide
      range of density values (0.6-1.4 g/cm3). However, the calculation was limited at
      rather higher density (>0.6 g/cm3) due to the difficulty of convergence, which is
      inherent to the hypernetted-chain (HNC) closure. The problem is overcome in this
      study by employing the Kovalenko-Hirata (KH) closure which hybridizes the HNC and
      the mean-spherical approximation (MSA). Here, we present the results for the
      thermodynamic range of densities from 0.025 to 1.0 g/cm3 and for temperatures
      from 300 to 800 K including the supercritical point.

PMID- 16623533
TI  - Comparison of atomic-level and coarse-grained models for liquid hydrocarbons from
      molecular dynamics configurational entropy estimates.
AB  - Molecular liquids can be modeled at different levels of spatial resolution. In
      atomic-level (AL) models, all (heavy) atoms can be explicitly simulated. In
      coarse-grained (CG) models, particles (beads) that represent groups of covalently
      bound atoms are used as elementary units. Ideally, a CG model should reproduce
      the thermodynamic and structural properties of the corresponding AL model after
      mapping to the lower-resolution scale. In the present work, two such models are
      investigated: (i) the classical GROMOS atomic-level model; (ii) a CG model
      recently proposed by Marrink et al., which maps approximately four non-hydrogen
      atoms to one bead [J. Phys. Chem. B 2004, 108, 750]. The study is restricted to n
      alkanes whose aliphatic fragments are abundantly found in lipids of biological
      interest. Additionally, cis-9-octadecene is included, as a template chain of the
      lipid dioleoylphosphatidylcholine (DOPC). The two representations of molecules in
      the liquid phase are compared in terms of average molecular structures, extent of
      configurational space sampled, and single-molecule entropies. An approximate
      method is used to estimate the rotational contributions to the absolute
      configurational entropy. Good correspondence between the AL and CG
      representations is found. The loss in configurational entropy due to the
      reduction in degrees of freedom upon coarse-graining of the model is estimated.

PMID- 16623532
TI  - Enthalpy-entropy contributions to the potential of mean force of nanoscopic
      hydrophobic solutes.
AB  - Entropic and enthalpic contributions to the hydrophobic interaction between
      nanoscopic hydrophobic solutes, modeled as graphene plates in water, have been
      calculated using molecular dynamics simulations in the isothermal-isobaric (NPT)
      ensemble with free energy perturbation methodology. We find the stabilizing
      contribution to the free energy of association (contact pair formation) to be the
      favorable entropic part, the enthalpic contribution being highly unfavorable. The
      desolvation barrier is dominated by the unfavorable enthalpic contribution,
      despite a fairly large favorable entropic compensation. The enthalpic
      contributions, incorporating the Lennard-Jones solute-solvent terms, largely
      determine the stability of the solvent separated configuration. We decompose the
      enthalpy into a direct solute-solute term, the solute-solvent interactions, and
      the remainder that contains pressure-volume work as well as contributions due to
      solvent reorganization. The enthalpic contribution due to changes in water-water
      interactions arising from solvent reorganization around the solute molecules is
      shown to have major contribution in the solvent induced enthalpy change.

PMID- 16623534
TI  - Triangle of liquid-gas states.
AB  - We demonstrate for the first time that (a) the straight line of the unit
      compressibility factor (Zeno line) tends asymptotically to the liquid branch of
      binodal at low temperatures, (b) the straight line with a half density has to be
      close to the average of vapor-liquid densities along the binodal curve
      (rectilinear diameter), and (c) the phase coexistence curves are inscribed into
      the right triangle in the density-temperature plane, which is formed by the Zeno
      line and by the segments which this line cuts off on the axes. These statements
      are confirmed for model systems and for a wide group of real substances (for the
      first time including metals: Hg, Cs, and Cu). Critical parameters of all
      substances under study are located in the vicinity of the triangle median, drawn
      to the density axis, with a dispersion on the order of 2 in reduced units.

PMID- 16623535
TI  - Three-dimensional description of the spontaneous onset of homochirality on the
      surface of a conglomerate crystal phase.
AB  - The spontaneous emergence of homochirality in an initially racemic system can be
      obtained in far-from-equilibrium states. Traditional models do not take into
      account the influence of inhomogeneities, while they may be of great importance.
      What would happen when one configuration emerges at one position, and the
      opposite one at another position? We present a discrete three-dimensional model
      of conglomerate crystallization, based on 1,1'-binaphthyl crystallization
      experiments, that takes into account the position and environment of every single
      elementary growth subunit. Stochastic simulations were performed to predict the
      evolution of the crystallization process. It is shown that the traditional view
      of the symmetry breaking can then be extended. Fluctuations of the fixed points
      related to inhomogeneities are observed, and complex behavior, such as local
      instabilities, transient structures, and chaotic behavior, can emerge. Our
      modeling indicates that such complex phenomena could cause large fluctuation of
      the final enantiomeric excess that is observed experimentally in binaphthyl
      crystallization. The results presented in this article show the importance of
      inhomogeneities in understanding enantiomeric excess generated in crystallization
      and the inadequacy of the models based on the assumption of homogeneity.

PMID- 16623536
TI  - Sampling of rare events using hidden restraints.
AB  - A method to enhance sampling of rare events is presented. It makes use of
      distance or dihedral-angle restraints to overcome an energy barrier separating
      two metastable states or to stabilize a transition state between the two
      metastable states. In order not to perturb these metastable end states
      themselves, a prefactor is introduced into the restraining energy function, which
      smoothly increases the weight of this function from zero to one at the transition
      state or on top of the separating energy barrier and then decreases the weight
      again to zero at the final state. The method is combined with multi
      configurational thermodynamic integration and applied to two biomolecular
      systems, which were difficult to treat using standard thermodynamic integration.
      As first example the free energy difference of a cyclic alpha-aminoxy-hexapeptide
      ion complex upon changing the ion from Cl- to Na+ was calculated. A large
      conformational rearrangement of the peptide was necessary to accommodate this
      change. Stabilizing the transition state by (hidden) restraints facilitates that.
      As a second example, the free energy difference between the 4C1 and the 1C4
      conformation of beta-D-glucopyranoside was calculated. In unrestrained
      simulations the change from the 4C1 into the 1C4 conformation was never observed
      because of the high energy barrier separating the two states. Using (hidden)
      restraints, the transition from the 4C1 into the 1C4 state and back could be
      enforced without perturbing the end states. As comparison, for the same
      transitions the potential of mean force as obtained by using dihedral-angle
      constraints is provided.

PMID- 16623537
TI  - Comparative studies on interactions of bovine serum albumin with cationic gemini
      and single-chain surfactants.
AB  - The interactions of bovine serum albumin (BSA) with cationic gemini surfactants
      alkanediyl-alpha,omega-bis(dodecyldimethylammonium bromide)
      [C12H25(CH3)2N(CH2)(S)N(CH3)2C12H25]Br2 (designated as C12C(S)C12Br2, S = 3, 6,
      and 12) and single-chain surfactant dodecyltrimethylammonium bromide (DTAB) have
      been studied with isothermal titration microcalorimetry, turbidity, fluorescence
      spectroscopy, and circular dichroism at pH 7.0. Comparing with DTAB,
      C12C(S)C12Br2 have much stronger binding ability with BSA to induce the
      denaturation of BSA at very low molar ratio of C12C(S)C12Br2/BSA, and
      C12C(S)C12Br2 have a much stronger tendency to form insoluble complexes with BSA.
      The binding of C12C(S)C12Br2 to BSA generates larger endothermic peaks. The first
      endothermic peak is much stronger than that of the second endothermic peak. The
      double charges and strong hydrophobicity of the gemini surfactants are the main
      reasons for these observations. In addition, the spectra results show that the
      binding of DTAB to BSA only promotes BSA unfolding and aggregation, whereas the
      secondary structure of BSA is possibly stabilized by a small amount of
      C12C(S)C12Br2 , even if the small amount of binding C12C(S)C12Br2 could induce
      the loss of the tertiary structure of BSA. This result may be related to the
      double tails of gemini surfactants, which may generate the hydrophobic linkages
      between the nonpolar residues of BSA.

PMID- 16623538
TI  - Generalized two-dimensional heterocorrelation analysis of spectrally resolved and
      temporally resolved fluorescence of the 8-anilino-1-naphthalenesulfonate
      apomyoglobin complex with pH perturbation.
AB  - We demonstrate two-dimensional heterocorrelation analysis between spectrally
      resolved and temporally resolved fluorescence to investigate the decay dynamics
      of the 8-anilino-1-naphthalenesulfonate- (ANS-) apomyoglobin complex. The dynamic
      changes of the lifetime components are disclosed across the emission spectrum
      with an external pH-perturbation. Two different fluorescence lifetime schemes of
      the ANS-apomyoglobin complex are revealed. From pH 8.5 to 4.5, the transition of
      protein conformation from the native state to the folding intermediate, a short
      lifetime component is found to correlate with a short-wavelength emission whose
      population diminishes with decreasing pH. The lifetime components reflect the
      excited-state populations of the nascent and the charge-transfer species. From pH
      4.2 to 1.0, the transition from the folding intermediate to the acid-unfolded
      state, the short lifetime is responsible for a long-wavelength emission and the
      fraction of this component increases when the solution becomes more acidic. In
      this pH range, the decay components reflect the ground-state populations of
      microenvironments. The relative decay dynamics across the emission spectrum are
      revealed without collecting decays at each wavelength. More importantly, these
      conclusions are reached without the necessity of statistical fitting of the decay
      data with an a priori decay model.

PMID- 16623539
TI  - Coupled membrane fluctuations and protein mobility in supported intermembrane
      junctions.
AB  - Junctions between lipid membranes make possible cell-free explorations of
      physical mechanisms that can contribute to protein and lipid organization at a
      variety of biophysical interfaces. Recent studies of mobile antibodies sandwiched
      between lipid bilayer membranes have shown that strong intermembrane adhesion and
      protein mobility alone are sufficient to drive inert proteins into micron-scale
      patterns of dense and sparse zones. Though the length scale of these patterns was
      suspected to be related to membrane rigidity, a quantitative understanding has so
      far been unavailable. We introduce data showing radially structured protein
      patterns that also demonstrate micron-scale organization. We then provide a
      simple model that relates the spectrum of membrane fluctuations to the observed
      protein distributions; in brief, only membrane modes that are slow enough to
      couple to the protein mobility drive intermembrane protein patterns.

PMID- 16623540
TI  - Stable gas-phase radical cations of dimeric tryptophan and tyrosine derivatives.
AB  - Stable radical cations of dimeric amino acid derivatives of tryptophan and
      tyrosine were generated by collision-induced dissociation of
      [Cu(II)(diethylenetriamine)(amino acid derivative)2]*2+. The yields of the dimer
      radical cations were dependent on both the auxiliary ligand and the tryptophan or
      tyrosine derivatives used. Amino acid derivatives with an unmodified carboxylic
      acid group did not generate dimer radical cations. For the amino acid derivatives
      Ac-Trp-OMe and Ac-Trp-NH2 (Ac is N-acetyl; OMe and NH2 are the methyl ester and
      amide modifications of the C-terminal carboxylic group), no auxiliary ligand was
      required for generating the dimer radical cations. Collision-induced dissociation
      of the [Cu(II)(amino acid derivative)4]*2+ precursor generated the dimer radical
      cation [(amino acid derivative)2]*+. Stabilizing interactions, most likely
      involving hydrogen bonding, between the two amino acid derivatives are proposed
      to account for observation of the dimer radical cations. Dissociation of these
      ions yields protonated or radical cationic amino acid derivatives; these
      observations are consistent with the expectation of proton competition between
      monomeric units, whose proton affinities were calculated using density functional
      theory.

PMID- 16623541
TI  - Effects of zwitterionic vesicles on the reactivity of benzoyl chlorides.
AB  - A systematic study on the solvolysis reaction of substituted benzoyl chlorides in
      the presence of zwitterionic vesicles of dipalmitoyl phosphatidylcholine (DPPC)
      has been performed. Size, shape, surface charge, and polarity of the interface of
      the vesicular aggregates were determined using various techniques. The
      application of the pseudophase formalism allowed us to obtain the thermodynamic
      and kinetic coefficients characteristic of the reaction. The effects of vesicular
      aggregates on the solvolysis of benzoyl chlorides, which are known to be
      sensitive to the physical properties of the medium, depend on the nature of the
      substrate. For benzoyl chlorides with electron-donating groups, which react
      predominantly through a dissociative mechanism which is strongly affected by
      medium properties, the rate constant decreases as the vesicle concentration
      increases. On the other hand, for benzoyl chlorides with electron-withdrawing
      groups, which react mainly via an associative pathway, DPPC vesicles catalyze the
      solvolysis reaction.

PMID- 16623542
TI  - Diphenylindane-based proteomimetics reproduce the projection of the i, i+3, i+4,
      and i+7 residues on an alpha-helix.
AB  - [structure: see text] The design of a nonpeptidic scaffold based on 4,7-diphenyl
      1,6-disubstituted indanes mimicking i, i+3, i+4, and i+7 residues of an alpha
      helix has been described, and its synthesis has been accomplished. This strategy
      makes general approaches possible to helix mimetic scaffolds that could be
      targeted to different proteins by changing the nature of the substituents.

PMID- 16623543
TI  - Novel bile acid-based cyclic bisimidazolium receptors for anion recognition.
AB  - [structure: see text] Novel deoxycholic acid-based cyclic receptors, 3 and 4,
      containing two imidazolium groups and m-xylene and p-xylene as spacers have been
      synthesized. These receptors bind anions through hydrogen bonds utilizing two
      imidazolium (C-H)(+) and inwardly directed methylene hydrogens of both acetyl
      groups. Receptor 3 shows a moderate selectivity for fluoride ion whereas receptor
      4 shows high affinity and selectivity for chloride ion in CDCl(3).

PMID- 16623545
TI  - A new specific mechanism for the acid catalysis of the addition step in the
      Baeyer-Villiger rearrangement.
AB  - [structure: see text] A new transition state of the addition step in the Baeyer
      Villiger reaction was found. The role of proton acceptor is played by the
      carbonyl oxygen atom, and the free energy barrier is 12.7 kcal/mol lower than
      that previously reported. This finding changes the mechanism for the acid
      catalysis and could be of interest for similar reactions in which it is known
      that such catalysis occurs, especially in nonpolar solvents.

PMID- 16623546
TI  - Functionalized nanodiamonds part 3: thiolation of tertiary/bridgehead alcohols.
AB  - [reaction: see text] Treatment of acyclic as well as polycyclic tertiary mono-
      and dihydroxy hydrocarbon derivatives with thiourea in the presence of
      hydrobromic and acetic acid represents a convenient one-step route to the
      respective tertiary thiols and dithiols. This procedure was used for the
      preparation of diamondoid thiols of diamantane, triamantane, [121]tetramantane,
      and others that are prospective nanoelectronic materials.

PMID- 16623544
TI  - TESOTf-induced rearrangement of quinols. Efficient construction of the fully
      functionalized carbon skeleton of the griseusins by a divergent-reconvergent
      approach.
AB  - [reaction: see text] The "reverse polarity" or "umpolung" strategy for the total
      synthesis of aryl C-glycosides was developed in the context of the antibiotic (-)
      griseusin B. Although a key reaction in a model sequence for the total synthesis
      produced two structurally divergent products, both were converted to the same
      advanced model intermediate that contains the complete carbon skeleton and
      (except for the extraneous oxygen substituent in the model series) the functional
      group pattern of the griseusins.

PMID- 16623547
TI  - Iron-catalyzed cross-coupling of imidoyl chlorides with Grignard reagents.
AB  - [reaction: see text] A general, high yielding rapid iron-catalyzed cross-coupling
      reaction between Grignard reagents and imidoyl chlorides is described. These
      reactions are typically completed within 5 min, resulting in high yields of 71
      96% using 5% iron catalyst in a THF-NMP solvent mixture. Functionalized imidoyl
      chlorides (e.g., R = CO(2)Me) gave excellent yields (89%).

PMID- 16623548
TI  - Novel methodology for the preparation of five-, seven-, and nine-membered fused
      rings on C60.
AB  - [reaction: see text] The photocycloaddition of dienyl cyclopropanes to C(60)
      gives a new synthetic approach to yield stereospecifically five-, seven-, and
      nine-membered [60]fullerene adducts. Our results suggest the formation of a
      biradical intermediate between the dienyl substrate and C(60). An electron
      transfer between the triplet excited state of C(60) and the dienyl substrate
      precedes the formation of the intermediate.

PMID- 16623550
TI  - Dual pathways for the desilylation of silylamines by singlet oxygen.
AB  - [reaction: see text] A kinetic and product study has been carried out for the
      reactions of silylamines 1a and 1b with (1)O(2) in MeCN and (80:20) MeCN-MeOH.
      Indications suggesting an electron-transfer step following exciplex (I) formation
      have been obtained. However, the fate of the radical cation is solvent dependent.
      The radical cation undergoes desilylation in MeCN-MeOH and deprotonation in MeCN.

PMID- 16623549
TI  - Construction of beta-haloenamides via direct copper-promoted coupling of lactams
      with 2-chloro and 2-bromo vinyliodides.
AB  - [reaction: see text] Cu(I)-catalyzed coupling of lactams with (E)-2
      chlorovinyliodides or (E)-2-bromovinyliodides produces the corresponding beta
      haloenamides in moderate to excellent yields.

PMID- 16623551
TI  - New air-stable catalysts for general and efficient suzuki-miyaura cross-coupling
      reactions of heteroaryl chlorides.
AB  - [reaction: see text] New air-stable PdCl(2){P(t)Bu(2)(p-R-Ph)}(2) (R = H, NMe(2),
      CF(3),) complexes represent simple, general, and efficient catalysts for the
      Suzuki-Miyaura cross-coupling reactions of aryl halides including five-membered
      heteroaryl halides and heteroatom-substituted six-membered heteroaryl chlorides
      with a diverse range of arylboronic acids. High product yields (89-99% isolated
      yields) and turn-over-numbers (10,000 TON) are observed.

PMID- 16623552
TI  - An intramolecular substitution of hydroperoxy-endoperoxide to a bis-endoperoxide.
AB  - [reaction: see text] A new and stereospecific synthesis for bis-endoperoxide has
      been developed starting from tetrahydronaphthalene. Photooxygenation of
      tetrahydronaphthalene resulted in the formation of hydroperoxy-endoperoxide. The
      bromination reaction of hydroperoxy-endoperoxide gave bis-endoperoxide, whose
      exact configuration has been determined by X-ray analysis. The lowest-energy
      conformer of bis-endoperoxide is the boat-chair form.

PMID- 16623553
TI  - Catalytic enantioselective 1,3-dipolar cycloaddition of azomethine ylides with
      vinyl sulfones.
AB  - [reaction: see text] A general protocol for the enantioselective catalytic 1,3
      dipolar cycloaddition of azomethine ylides with aryl vinyl sulfones is described.
      Nearly complete exo selectivity and enantioselectivities up to 85% ee are
      attained with Cu(CH(3)CN)(4)ClO(4)/Taniaphos as the catalyst system. The
      resulting enantioenriched 3-sulfonyl cycloadducts are versatile intermediates in
      the synthesis of 2,5-disubstituted pyrrolidines.

PMID- 16623554
TI  - Design and synthesis of potent cystine-free cyclic hexapeptide agonists at the
      human urotensin receptor.
AB  - [structure: see text] Cyclic hexapeptides, incorporating a dipeptide unit in
      place of the disulfide bond found in urotensin, were prepared and screened at the
      human urotensin receptor. The bridging dipeptide unit was found to influence
      dramatically the affinity for the urotensin receptor. Alanyl-N-methylalanyl and
      alanylprolyl dipeptide bridges failed to afford active ligands, while the alanyl
      alanyl unit yielded a ligand with submicromolar affinity for the urotensin
      receptor. Further development led to a hexapeptide agonist with nanomolar
      affinity (2.8 nM).

PMID- 16623555
TI  - Resin-bound dynamic combinatorial chemistry.
AB  - [reaction: see text] Dynamic combinatorial chemistry (DCC) is a promising
      technique for receptor-aided selection of high-affinity ligands from
      equilibrating combinatorial libraries. Identification of the specific ligand(s)
      selected is often challenging, however, due to difficulties associated with
      chromatographic separation and/or mass degeneracy within the library. Herein, we
      describe proof-of-concept experiments demonstrating a new technique termed resin
      bound DCC (RB-DCC), which provides a solution to this problem.

PMID- 16623556
TI  - Significant improvement of antifungal activity of polyene macrolides by
      bisalkylation of the mycosamine.
AB  - [reaction: see text] New derivatives of Amphotericin B (AmB) were synthesized
      through a double reductive alkylation of the mycosamine. These derivatives of AmB
      displayed superior antifungal activity against Saccharomyces cerevisiae wild-type
      strain and especially in the case of an AmB-resistant Candida albicans strain.
      Moreover, these compounds are potential drug candidates because of significantly
      reduced hemotoxicity compared to AmB. Furthermore, the same mycosamine
      modification can be applied to other polyene macrolides such as Nystatin and
      Pimaricin to improve their antifungal activity.

PMID- 16623557
TI  - Generation-independent dimerization behavior of quadruple hydrogen-bond
      containing oligoether dendrons.
AB  - [reaction: see text] A new series of self-assembling G1-G3 dendronized dimers
      bearing oligoether dendrons and a dimeric 2-ureido-4-pyrimidinone (UPy) quadruple
      hydrogen-bonding core were prepared and characterized. It was found that the
      nonpolar microenvironment created by the dendrons preserved the UPy unit in its
      DDAA tautomeric form. As a result, the stabilities of the dimers were
      exceptionally strong for all three generations (K(dim) > 2 x 10(7) M(-)(1) in
      CDCl(3) at 25 degrees C). Furthermore, the steric size of the dendrons did not
      exhibit a significant effect on their dimerization behavior.

PMID- 16623558
TI  - Synthesis of glycosyl phosphates from 1,2-orthoesters and application to in situ
      glycosylation reactions.
AB  - [reaction: see text] A series of glycosyl phosphates were prepared in high yield
      by treatment of the corresponding 1,2-orthoesters with dibutyl phosphate.
      Glycosyl phosphates are efficient glycosylating agents even when used in crude
      form or when generated in situ. The immunodominant epitope trirhamnoside of group
      B Streptococcus was prepared to demonstrate the synthetic utility of the method.

PMID- 16623559
TI  - Solid-phase synthesis of oligo(p-benzamide) foldamers.
AB  - [reaction: see text] A coupling protocol has been developed which allows the
      synthesis of oligo(p-benzamide)s on solid support. Aromatic carboxylic acids are
      activated in situ with thionyl chloride and used to acylate secondary aromatic
      amines. N-p-Methoxy benzyl (PMB) as well as N-hexyl protected monomers were
      investigated. Heterosequences of both monomers were synthesized. Such nanoscale
      objects are important building blocks for supramolecular chemistry.

PMID- 16623560
TI  - Total synthesis of (+/-)-galanthamine.
AB  - [reaction: see text] A practical and efficient total synthesis of (+/-)
      galanthamine was achieved from commercially available materials through a novel
      approach, in which the construction of its core structure and the special allylic
      alcohol group were based on a successive semipinacol
      rearrangement/desilyation/cyclization and Saegusa-Ito oxidation, respectively.

PMID- 16623561
TI  - A retro-Claisen approach to dolabriferol.
AB  - [reaction: see text] The protected precursor 30 to dolabriferol was generated by
      a DBU-induced, ester-forming, retro-Claisen process. The required linear carbon
      chain present in 22 was synthesized by a stereoselective lithium aldol reaction.
      The necessary aldehyde and ketone fragments were synthesized using
      stereocontrolled aldol reactions with the ethyl (S)-lactate derived ketone 13.

PMID- 16623562
TI  - Highly efficient synthesis and solid-state characterization of 1,2,4,5
      tetrakis(alkyl- and arylamino)benzenes and cyclization to their respective
      benzobis(imidazolium) salts.
AB  - [reaction: see text] New synthetic methodology to a variety of 1,2,4,5
      tetraaminobenzenes and their corresponding benzobis(imidazolium) salts has been
      accomplished. Palladium-catalyzed coupling of various 1,2,4,5-tetrabromo- or
      1,2,4,5-tetrachlorobenzenes with aryl- or tert-alkylamines afforded the
      respective tetrakis(N-substituted)aminobenzenes in excellent yields. This enabled
      comparative solid-state structural analyses of this elusive class of electron
      rich arenes with their oxidized derivatives. The tetraamines were found to
      undergo formylative cyclization to the corresponding benzobis(imidazolium) salts
      in good to excellent yields.

PMID- 16623563
TI  - 2,6,10-Tris(dianisylaminium)-3,7,11- tris(hexyloxy)triphenylene: a robust quartet
      molecule at room temperature.
AB  - [reaction: see text] A new triradical molecule, 2,6,10-tris(dianisylaminium)
      3,7,11-tris(hexyloxy)triphenylene 1(3+), was synthesized by oxidative
      trimerization, palladium-catalyzed amination, and subsequent oxidation. It was
      chemically stable with a half-life > 1 month and displayed the magnetic parameter
      of S = 3/2 even at room temperature.

PMID- 16623564
TI  - Copper-catalyzed cycloisomerizations of 5-en-1-yn-3-ols.
AB  - [reaction: see text] The Cu(I)-catalyzed cycloisomerization of tertiary 5-en-1-yn
      3-ols with an 1,2-alkyl shift affords stereoselectively tri- and tetracyclic
      compounds of high molecular complexity. These results are in agreement with a
      mechanism in which the cyclopropanation precedes the rearrangement.

PMID- 16623566
TI  - A dendrimer approach to high-spin polycarbenes. Conversion of connectivity from
      disjoint to non-disjoint by perturbation of nonbonding molecular orbital
      coefficients.
AB  - [structure: see text] Pentakis(diazo) compound was prepared by coupling 3,5-bis[4
      [diazo(4-tert-butyl-2,6-dimethylphenyl)methyl]-3,5
      dibromophenylethynyl]phenylacetylene with bis(4-iodo-2,6
      dimethylphenyl)diazomethane under Sonogashira reaction conditions.
      Pentakis(carbene) generated by irradiation of the pentakis(diazo) compound was
      shown to have a high-spin state with S = 4.4 at 2.0 K.

PMID- 16623565
TI  - A novel generation of indole-2,3-quinodimethanes.
AB  - [reaction: see text] A novel and efficient procedure for the generation of the
      reactive indole-2,3-quinodimethane intermediates from the allenylanilines is
      described. The indole-2,3-quinodimethane intermediates were captured by several
      dienophiles to afford the corresponding tetrahydro- and dihydrocarbazole
      derivatives. This method is significantly different from the previously reported
      ones, which involve the 1,4-elimination or its related reactions of the indole
      derivatives that possess suitable substituents at both the C-2 and C-3 positions.

PMID- 16623567
TI  - Liquid-crystalline fullerodendrimers which display columnar phases.
AB  - [structure: see text] The title compounds were synthesized by applying the 1,3
      dipolar cycloaddition reaction of aldehyde-based poly(benzyl ether) dendrimers
      and sarcosine (N-methylglycine) to [60]fullerene (C(60)). The dendritic building
      blocks used to functionalize C(60) displayed cubic and hexagonal columnar phases.
      The fullerene derivatives showed rectangular columnar phases of c2mm symmetry.

PMID- 16623568
TI  - Tetraalkoxyphenanthrene: a new precursor for luminescent conjugated polymers.
AB  - [reaction: see text] We have developed a convenient synthesis of
      tetraalkoxyphenanthrene derivatives and demonstrated their use to form
      luminescent conjugated oligomers and polymers. Palladium-catalyzed cross-coupling
      reactions of 2,7-diiodo-3,6-dimethoxy-9,10-di(2-ethylhexyloxy)phenanthrene
      produced high molecular weight poly(p-phenylene ethynylene)s and low molecular
      weight poly(p-phenylene vinylene)s. These new polymers, which are luminescent in
      the solid state and in solution, may be useful for developing LED or solar cell
      devices, or in chemical sensors.

PMID- 16623569
TI  - Self-assembly of triptycene-based cylindrical macrotricyclic host with
      dibenzylammonium ions: construction of dendritic [3]pseudorotaxanes.
AB  - [reaction: see text] It was found that a cylindrical macrotricyclic host
      containing two dibenzo[24]crown-8 cavities could self-assemble with two
      dibenzylammonium salts to form a stable 1:2 complex in solution and in the solid
      state, in which multiple hydrogen-bonding and pi-pi stacking interactions between
      the host and the guest played an important role. Furthermore, a series of
      dendritic pseudorotaxanes were constructed and structurally studied.

PMID- 16623570
TI  - Copper(II)-mediated cross-coupling of arylboronic acids and 2(1H)-pyrazinones
      facilitated by microwave irradiation with simultaneous cooling.
AB  - [reaction: see text] Optimized conditions for the decoration of the 2(1H)
      pyrazinone scaffold were developed by applying the Chan-Lam protocol. It was
      demonstrated that this Cu(II)-mediated cross-coupling reaction resulted in
      significantly improved yields and rates when performed under microwave
      irradiation with simultaneous cooling at 0 degrees C, applying a mixture of bases
      Et(3)N/pyridine.

PMID- 16623571
TI  - Stereoselective cascade reactions that incorporate a 7-exo acyl radical
      cyclization.
AB  - [reaction: see text] Radical cascades that feature a 7-exo acyl radical
      cyclization followed by a 6-exo or 5-exo alkyl radical cyclization proceed with
      very good yields and diastereoselectivities. Two stereocenters are created by the
      reaction, and a single isomeric product was obtained from each of the five
      substrates examined. The relative configurations of the products are consistent
      with cyclizations occurring via chairlike or pseudochairlike transition states.

PMID- 16623572
TI  - Operationally simple, efficient, and diastereoselective synthesis of cis-2,6
      disubstituted-4-methylene tetrahydropyrans catalyzed by triflic acid.
AB  - [reaction: see text] A highly efficient (0.01 mol % of TfOH), operationally
      simple (room temperature, inexpensive, and commercially available catalyst), and
      diastereoselective (up to >98% de) method for Bronsted acid-catalyzed reaction of
      enol ethers to form cis-2,6-disubstituted tetrahydropyrans is disclosed.

PMID- 16623573
TI  - Isonitrile trapping reactions under thermolysis of alkoxyamines for the synthesis
      of quinolines.
AB  - [reaction: see text] An efficient tandem radical process comprising a thermal
      alkoxyamine homolysis, an isonitrile trapping reaction, a 5-exo-trig cyclization,
      and a homolytic aromatic substitution leads to substituted dihydroquinolines.
      Depending on the substituent R(1), oxidation to dihydro-1H
      cyclopenta[b]quinolines (for R(1) = aryl) or tautomerization to tetrahydro-1H
      cyclopenta[b]quinolines (for R(1) = CO(2)Me, CN) occurs. The heterocycles are
      obtained in moderate to good yields. Upon using microwave-induced heating, the
      reaction time can be shortened from 3 days to 30 min.

PMID- 16623574
TI  - Kinetic resolution of diols and pyridyl alcohols by Cu(II)(borabox)-catalyzed
      acylation.
AB  - [reaction: see text] Boron-bridged bisoxazoline (borabox) ligands have been used
      in the copper(II)-catalyzed benzoylation of pyridyl alcohols and 1,2-diols.
      Efficient kinetic resolution of 1,2-diols was achieved using both borabox and
      bisoxazoline (box) ligands. Borabox ligands induced high selectivities in the
      benzoylation of suitable pyridyl alcohols, where they outperformed bisoxazolines.
      In addition, highly enantioselective Cu(II)(borabox)-catalyzed benzoylation has
      been used for the synthesis of both enantiomers of a pyridyl alcohol.

PMID- 16623576
TI  - Pd(0)-Catalyzed PMHS reductions of aromatic acid chlorides to aldehydes.
AB  - [reaction: see text] Contrary to previous reports, polymethylhydrosiloxane (PMHS)
      under Pd(0) catalysis can efficiently reduce aryl acid chlorides to their
      corresponding aldehydes without requiring an additional reductant, provided the
      reactions are run in the presence of fluoride.

PMID- 16623575
TI  - Synthesis of a biotin-derived alkyne for pd-catalyzed coupling reactions.
AB  - [reaction: see text] An efficient synthesis of a terminal alkyne derived from d
      biotin was developed to provide an alternative for carboxyl-based biotinylation.
      This approach was illustrated by the preparation of alkyne- and alkene-linked
      phenylalanine derivatives using palladium-catalyzed Sonogashira and Oh
      methodology. (Strept)avidin binding was observed using soluble and immobilized
      receptors. These results demonstrate the applicability of carbon-linked biotin
      derivatives for use in affinity-based purification and bioanalytical
      applications.

PMID- 16623577
TI  - Epoxysilane rearrangement induced by a carbanion generated by conjugate addition
      of enolates of chloroacetate and alpha-chloroacetamides: formation of
      functionalized cyclopropane derivatives.
AB  - [reaction: see text] Reaction of an enoate bearing an epoxysilane moiety at the
      alpha-position with lithium enolate of 2-chloroacetamide afforded highly
      functionalized cyclopropane derivatives via a tandem process that involves
      Michael addition, ring opening of the epoxide, Brook rearrangement, and
      intramolecular alkylation.

PMID- 16623578
TI  - Design, synthesis, and biological evaluation of a potent, PKC selective, B-ring
      analog of bryostatin.
AB  - [structure: see text] The first member of a new class of five-membered B-ring
      analogs of bryostatin has been synthesized and tested for its ability to bind and
      translocate protein kinase C (PKC). This synthesis extends the utility of our
      previously introduced macrotransacetalization strategy to the formation of five
      membered dioxolane B-ring analogs. This analog exhibits potent, single-digit
      nanomolar affinity to PKC and selectively translocates novel PKC isozymes.

PMID- 16623579
TI  - Hybridization of pyrrolidinyl peptide nucleic acids and DNA: selectivity, base
      pairing specificity, and direction of binding.
AB  - [structure: see text] A mixed-base, beta-amino acid containing, pyrrolidinyl
      peptide nucleic acid (PNA) binds strongly and selectively to complementary DNA in
      an exclusively antiparallel fashion. The PNA-DNA binding specificity strictly
      follows the Watson-Crick base-pairing rules.

PMID- 16623580
TI  - Synthesis of the 3-aza-[7]-paracyclophane core of haouamine A and B.
AB  - [reaction: see text] The synthesis of the highly strained 3-aza-[7]
      paracyclophane core of haouamines A and B is based on a macrocyclization
      aromatization protocol, allowing for a stepwise increase in ring strain and
      establishing the oxygenation pattern of the natural products.

PMID- 16623581
TI  - New method based on 1-(trimethysilyl)alk-1-yne to prepare 1,4-skipped diynes.
AB  - [reaction: see text] We have developed a novel reaction between a terminal TMS
      alkyne and a propargyl halide in the presence of a fluoride source and a
      catalytic amount of copper iodide to prepare 1,4-skipped diynes with good yields
      and in mild conditions. We have shown that this reaction also works very well
      with germanium and tin derivatives as an alternative to silicon. This new method
      can be useful for the synthesis of polyunsaturated fatty acids.

PMID- 16623582
TI  - Switching of product's chirality in diastereodifferentiating [2+2]
      photocycloaddition of (E)- versus (Z)-stilbene to chiral fumarate upon direct and
      charge-transfer-band excitation.
AB  - [reaction: see text] Diastereodifferentiating [2+2] photocycloadditions of (E)-
      and (Z)-stilbenes to bis((R)-1-methylpropyl) fumarate were performed through the
      direct excitation of stilbenes and the selective excitation of the charge
      transfer (CT) complex at various temperatures. The geometrical isomers of
      stilbene afforded the opposite diastereomers of mu-truxinate in both excitation
      modes, with a dramatic decrease in the product's diastereoselectivity upon
      prolonged irradiations.

PMID- 16623583
TI  - Desymmetrization of cyclic anhydrides using dihydroxy compounds: selective
      synthesis of macrocyclic tetralactones.
AB  - [reaction: see text] The desymmetrization of cyclic anhydrides is carried out
      using dihydroxy compounds. A mild route to synthesize fused saturated/unsaturated
      macrocyclic tetralactones with different ring sizes (20-34) having a wide variety
      of spacers is described. The structure is confirmed by the representative single
      crystal X-ray analysis. The multiple reduction of unsaturated macrocyclic
      tetralactones is also illustrated. This method is mild, selective, and efficient
      and achieves high yield.

PMID- 16623584
TI  - Synthesis of tris(tetrathiafulvaleno)dodecadehydro- [18]annulenes and their self
      assembly.
AB  - [reaction: see text] Synthesis of electroactive
      tris(tetrathiafulvaleno)dodecadehydro[18]annulenes with ester substituents has
      been carried out with palladium-mediated cyclotrimerization of 4,5-diethynyl
      TTFs. The TTF[18]annulenes produce stacked dimmers in solution and exhibit
      solvatochromism and thermochromism. The TTF[18]annulene-hexabutyl ester forms a
      molecular wire from an aqueous THF solution with cooperative S-S and pi-pi
      stacking interactions.

PMID- 16623585
TI  - Design of a small-molecule catalyst using intramolecular cation-pi interactions
      for enantioselective Diels-Alder and Mukaiyama-Michael reactions: L-DOPA-derived
      monopeptide.Cu(II) complex.
AB  - [reaction: see text] We have designed a small-molecule artificial metalloenzyme
      that is prepared in situ from Cu(OTf)(2) or Cu(NTf(2))(2) (1.0 equiv) and l-DOPA
      derived monopeptide (1.1 equiv). This catalyst (2-10 mol %) is highly effective
      for the enantioselective Diels-Alder (DA) and Mukaiyama-Michael (MM) reactions
      with alpha,beta-unsaturated 1-acyl-3,5-dimethylpyrazoles. The present results
      demonstrate that cation-pi interactions may be available for controlling the
      conformation of sidearms of chiral ligands, and monopeptides are readily tunable
      ligands that include only one chiral center.

PMID- 16623586
TI  - Stereoselective synthesis of the atropisomers of myristinin B/C.
AB  - [reaction: see text] The first stereoselective synthesis of a potent DNA damaging
      agent, (-)-myristinin B/C, has been accomplished. This efficient synthesis
      allowed for unambiguous confirmation of the structure and absolute
      stereochemistry of the atropisomeric natural product. The antipode, (+)
      myristinin B/C, was also synthesized, providing ample material for biological
      evaluation of both enantiomers.

PMID- 16623587
TI  - Mild and direct conversion of quinoline N-oxides to 2-amidoquinolines with
      primary amides.
AB  - [reaction: see text] A simple, one-pot procedure is described for the direct
      conversion of quinoline N-oxides to alpha-amidoquinolines with primary amides.
      This methodology is complimentary to the Abramovich reaction, which is limited to
      the introduction of secondary amides via imidoyl chlorides. Although reaction
      conditions are quite similar, omission of the base is key for successful reaction
      with primary amides, which were found not to proceed through the intermediacy of
      an imidoyl chloride but rather through an acyl isocyanate.

PMID- 16623588
TI  - Simultaneous protection and activation of amino acids using propargyl
      pentafluorophenyl carbonate.
AB  - [reaction: see text] A very efficient method for the simultaneous protection of
      the amino group and activation of the carboxyl group of amino acids is reported
      using propargyl pentafluorophenyl carbonate (PocOPfp). The amino group is
      protected as a propargyloxycarbonyl (Poc) derivative, and the carboxyl group is
      activated as a pentafluorophenyl ester. The yields obtained are good to excellent
      ranging from 60 to 87%.

PMID- 16623589
TI  - Dichotomains A and B: two new highly oxygenated phenolic derivatives from
      Dicranopteris dichotoma.
AB  - [structure: see text] Dichotomains A (1) and B (2), two new highly oxygenated
      phenolic derivatives that feature a spirodilactone moiety in their structures,
      were isolated from the fronds of Dicranopteris dichotoma. Their structures were
      elucidated on the basis of NMR and MS spectroscopic data, and the stereochemistry
      of 1 was finally determined by single-crystal X-ray diffraction. Compound 2
      showed weak anti-HIV-1 activity.

PMID- 16623590
TI  - Stereoselective functionalization of beta-iodo-alpha,beta-unsaturated ketones via
      an iodine-copper exchange reaction.
AB  - [reaction: see text] Beta-iodo-alpha,beta-unsaturated carbonyl compounds undergo
      a stereoselective iodine-copper exchange reaction with (Nphyl)(2)CuLi, providing
      the corresponding alkenyl cuprates with retention of the double bond
      configuration. No competitive addition/elimination was observed, and the
      resulting cuprates were successfully functionalized with various electrophiles.

PMID- 16623591
TI  - A versatile and general one-pot method for synthesizing bis-spiroketal motifs.
AB  - [reaction: see text] A versatile and general method for the biomimetic
      construction of [5,5,5]- and [6,5,6]-bis-spiroketals, starting from easily
      accessible furan nuclei, by means of a powerful one-pot singlet oxygen-mediated
      cascade sequence is reported.

PMID- 16623592
TI  - Gold-catalyzed heterocycle synthesis using homopropargylic ethers as latent
      electrophiles.
AB  - [reaction: see text] Homopropargylic ethers with pendent nucleophiles, when
      subjected to Au catalysts in aqueous solvent, provide heterocyclic ketones. The
      reactions are efficient, tolerant of functionality and ambient atmosphere, and
      operationally simple. Diastereoselectivity can be predicted on the basis of
      product thermodynamics. This process demonstrates the viability of
      homopropargylic ethers to serve as latent electrophiles that can be unraveled
      under highly selective conditions to promote heterocycle formation through
      nucleophilic additions to alpha,beta-unsaturated ketones.

PMID- 16623593
TI  - Water-triggered and gold(I)-catalyzed cascade addition/cyclization of terminal
      alkynes with ortho-alkynylaryl aldehyde.
AB  - [reaction: see text] A highly efficient alkynylation-cyclization of terminal
      alkynes with ortho-alkynylaryl aldehydes leading to 1-alkynyl-1H-isochromenes was
      developed by using a gold-phosphine complex as catalyst in water. The reaction
      was dually promoted by an electron-donating phosphine ligand and water and was
      chelation-controlled.

PMID- 16623594
TI  - Gold(I)-catalyzed stereoselective formation of functionalized 2,5-dihydrofurans.
AB  - [reaction: see text] A study concerning the gold(I)-catalyzed rearrangement of
      butynediol monobenzoates into functionalized 2,5-dihydrofurans is described. The
      mild reaction conditions employed allow the efficient and rapid stereoselective
      synthesis of a variety of 2,5-dihydrofurans via a sequence of two gold(I)
      catalyzed isomerization steps.

PMID- 16623597
TI  - Invasive plant suppresses the growth of native tree seedlings by disrupting
      belowground mutualisms.
AB  - The impact of exotic species on native organisms is widely acknowledged, but
      poorly understood. Very few studies have empirically investigated how invading
      plants may alter delicate ecological interactions among resident species in the
      invaded range. We present novel evidence that antifungal phytochemistry of the
      invasive plant, Alliaria petiolata, a European invader of North American forests,
      suppresses native plant growth by disrupting mutualistic associations between
      native canopy tree seedlings and belowground arbuscular mycorrhizal fungi. Our
      results elucidate an indirect mechanism by which invasive plants can impact
      native flora, and may help explain how this plant successfully invades relatively
      undisturbed forest habitat.

PMID- 16623598
TI  - A nonparametric test reveals selection for rapid flowering in the Arabidopsis
      genome.
AB  - The detection of footprints of natural selection in genetic polymorphism data is
      fundamental to understanding the genetic basis of adaptation, and has important
      implications for human health. The standard approach has been to reject
      neutrality in favor of selection if the pattern of variation at a candidate locus
      was significantly different from the predictions of the standard neutral model.
      The problem is that the standard neutral model assumes more than just neutrality,
      and it is almost always possible to explain the data using an alternative neutral
      model with more complex demography. Today's wealth of genomic polymorphism data,
      however, makes it possible to dispense with models altogether by simply comparing
      the pattern observed at a candidate locus to the genomic pattern, and rejecting
      neutrality if the pattern is extreme. Here, we utilize this approach on a truly
      genomic scale, comparing a candidate locus to thousands of alleles throughout the
      Arabidopsis thaliana genome. We demonstrate that selection has acted to increase
      the frequency of early-flowering alleles at the vernalization requirement locus
      FRIGIDA. Selection seems to have occurred during the last several thousand years,
      possibly in response to the spread of agriculture. We introduce a novel test
      statistic based on haplotype sharing that embraces the problem of population
      structure, and so should be widely applicable.

PMID- 16623599
TI  - The assembly of diverse immune receptors is focused on a polar membrane-embedded
      interaction site.
AB  - The majority of receptors responsible for activation of distinct cell types
      within the immune system assemble with dimeric signaling modules through
      interaction of a basic transmembrane residue with a pair of acidic residues of
      the signaling dimer. Because assembly of other membrane proteins requires
      specific interactions along extended stretches of transmembrane helices, we
      examined how transmembrane sequences flanking the polar interaction site
      contribute to assembly for three receptors that associate with different
      signaling modules-the natural killer cell receptors KIR and NKG2D and the Fc
      receptor for IgA, FcalphaRI. The KIR and NKG2D receptors assembled with the DAP12
      and DAP10 dimers, respectively, even when the entire KIR or NKG2D transmembrane
      domains were replaced by polyleucine sequences with a properly positioned basic
      residue. In contrast, a high degree of specificity for the basic side chain could
      be observed because the KIR-DAP12 and FcalphaRI-Fcgamma interactions favored
      lysine or arginine, respectively. Steric hindrance among incompatible extra
      membranous domains and competition for signaling modules also contributed to
      specificity of assembly. These results demonstrate that these interactions are
      focused on the polar site created by three ionizable transmembrane residues, and
      explain how the DAP12 and Fcgamma signaling modules can assemble with large, non
      overlapping sets of receptors that have highly divergent transmembrane sequences.

PMID- 16623601
TI  - Depression and primary care: drowning in the mainstream or left on the banks?
AB  - OBJECTIVE: To discuss the treatment, barriers, and successful strategies to treat
      depression in a primary care setting. SUMMARY: Historical, conceptual, and
      individual barriers hinder the treatment of depression. Additionally, a lack of
      clarity about whether the responsibility for care lies with primary care or
      behavioral health providers further leads to fragmented and uncoordinated
      systems. Depression is a chronic illness, not unlike diabetes, heart failure, and
      asthma. Therefore, disease models used to treat these chronic illnesses can also
      be applied to successfully treat depression. CONCLUSION: Appropriately managing
      patients with depression and other behavioral health conditions will require
      changing the entire health care system. Future strategies should include
      developing a continual quality improvement process, developing bridges between
      behavioral health and primary care, eliminating clinical and financial barriers
      between systems, and viewing the mind and body as a whole.

PMID- 16623600
TI  - Intermingling of chromosome territories in interphase suggests role in
      translocations and transcription-dependent associations.
AB  - After mitosis, mammalian chromosomes partially decondense to occupy distinct
      territories in the cell nucleus. Current models propose that territories are
      separated by an interchromatin domain, rich in soluble nuclear machinery, where
      only rare interchromosomal interactions can occur via extended chromatin loops.
      In contrast, recent evidence for chromatin mobility and high frequency of
      chromosome translocations are consistent with significant levels of chromosome
      intermingling, with important consequences for genome function and stability.
      Here we use a novel high-resolution in situ hybridization procedure that
      preserves chromatin nanostructure to show that chromosome territories intermingle
      significantly in the nucleus of human cells. The degree of intermingling between
      specific chromosome pairs in human lymphocytes correlates with the frequency of
      chromosome translocations in the same cell type, implying that double-strand
      breaks formed within areas of intermingling are more likely to participate in
      interchromosomal rearrangements. The presence of transcription factories in
      regions of intermingling and the effect of transcription impairment on the
      interactions between chromosomes shows that transcription-dependent
      interchromosomal associations shape chromosome organization in mammalian cells.
      These findings suggest that local chromatin conformation and gene transcription
      influence the extent with which chromosomes interact and affect their overall
      properties, with direct consequences for cell-type specific genome stability.

PMID- 16623602
TI  - Primary care physician perspective on management of patients with depression.
AB  - OBJECTIVE: To discuss the relationship between the primary care physician and
      other health care professionals and best practice strategies in the management of
      depression. SUMMARY: Useful chronic clinical models can transform a visit between
      a patient with depression and the primary care provider from an unfocused
      encounter to one that is anticipated, planned, and productive. With the proper
      decision and organizational support to manage their patients with depression,
      primary care providers will have the increased confidence to treat these patients
      and have more knowledge about the treatment plan, whether that is a referral or
      continuation of treatment in the provider.s office. CONCLUSION: The primary care
      provider must recognize that he or she cannot work alone. In addition to decision
      support and clinical information systems, there needs to be a delivery system
      that supports a depression care manager and identifies the patient as the key
      player in the system. Participation and cooperation by the entire health care
      system will determine the success of such depression care models.

PMID- 16623603
TI  - Can mental health integration in a primary care setting improve quality and lower
      costs? A case study.
AB  - OBJECTIVE: To describe the successful implementation of an evidence-based,
      integrated quality improvement mental health program in a primary care setting.
      SUMMARY: Intermountain Healthcare (IHC) has aligned resources around a conceptual
      framework that emphasizes clinic and community accountability, family and
      consumer health focused on recovery rather than disease, and enhanced decision
      making through partnerships and automation. The mental health integration system
      includes an integrated team led foremost by the patient and family with vital
      defined roles for primary care providers, care managers, psychiatrists, advanced
      practice registered nurses, support staff, and the National Alliance for the
      Mentally Ill. Pharmacists have assumed training functions on the team and have
      the potential to play more vital roles. CONCLUSION: The IHC experience
      demonstrates that mental health services can be effectively integrated into
      everyday practice in a primary care setting. Clinical and financial burden can be
      decreased for the health care team, patients, and family.

PMID- 16623604
TI  - The patient experience with the mental health system: a focus on integrated care
      solutions.
AB  - OBJECTIVE: To discuss the benefits of working with a multidisciplinary team from
      the patient and family perspective. SUMMARY: According to patients and their
      families, stigma is the primary barrier hindering treatment for depression and is
      followed by a web of access to care, mental health parity, and medication issues.
      The Mental Health Integration program strives to eliminate these barriers by
      emphasizing consumer- or patient-driven treatment, family support, and community
      based solutions. CONCLUSION: Working with a recovery model--"You are not alone,
      treatment works, recovery is possible, and there is hope"--the National Alliance
      on Mental Illness brings the family and consumer voice into the Mental Health
      Integration program, with the intention of effecting more widespread impact.

PMID- 16623605
TI  - Managing depressed patients with comorbidities and dual-eligibility benefit
      status.
AB  - OBJECTIVE: To discuss the challenges and requirements in developing and
      implementing strategies for the appropriate management of depression in a
      subpopulation of dual-eligible patients with comorbidities. SUMMARY: Treating
      patients with comorbidities who are dually eligible for Medicare and Medicaid
      services is challenging. In this vulnerable population, condition management
      strategies should address new patient cost-sharing responsibilities, improve or
      minimize the disruptions in access to medications, monitor for potential
      adherence issues, and, most importantly, strive to maintain, if not improve,
      overall health outcomes. Complicating these essential strategies are concerns
      about defining who is responsible for providing treatment to dual-eligible
      patients and the potential loss of vital services at various levels, including
      transition of care or the possible discontinuation of or severe limitations on
      reimbursement for key services. CONCLUSION: Condition management strategies
      should be developed to deal with the unique needs of the dual-eligible population
      to ensure continuity of care. Additionally, an organizational infrastructure is
      necessary to give providers useful tools to help them deliver better-coordinated
      care to the dual-eligible population that struggles with depression.

PMID- 16623606
TI  - Challenges of program implementation in a managed care environment: a case study
      in measuring medication persistence.
AB  - OBJECTIVE: To describe the challenges of implementing a disease management
      program in a managed care environment. SUMMARY: A key element in the successful
      management of depression is ensuring persistent consumption of medication
      throughout the duration of a standard course of therapy. However, treating
      physicians rarely have easy access to the exact records necessary to determine
      medication persistence. Prescription claims databases do contain this
      information. Properly identifying problem consumption patterns from these data is
      one of the most valuable services that managed care pharmacists can provide in a
      disease management program. The experiences of Aetna Inc. in implementing a
      depression management program illustrate some of the most important factors to be
      considered when designing a program: obtaining approval from senior management,
      measuring baseline performance before program initiation, selecting plan members
      and physicians based on patterns of consumption in prescription claims data, and
      quantifying effectiveness. CONCLUSION: A visual representation of prescription
      refill dates and quantities available in prescription claims databases allowed
      member physicians to determine, at a glance, each patient.s medication
      persistence. Such representations of data are valuable for helping identify
      problem consumption patterns that require further analysis, such as noncontinuous
      treatment, low usage, and nonpersistence. However, such data are not recommended
      for use in a vacuum. that excludes considerations such as therapeutic indication
      and environment.

PMID- 16623607
TI  - Factors associated with initiation with atomoxetine versus stimulants in the
      treatment of adults with ADHD: retrospective analysis of administrative claims
      data.
AB  - OBJECTIVE: To determine which factors are associated with use of atomoxetine
      (ATX) relative to stimulant medications (STIMs) for treatment initiation in
      adults with attention-deficit/hyperactivity disorder (ADHD). A similar
      exploratory analysis of the use of ATX versus STIMs in children has been
      published previously. METHODS: This was an exploratory analysis using a
      retrospective observational cohort design applied to administrative pharmacy and
      medical claims from an integrated managed care database. Patients were identified
      if they had at least 1 administrative claim with a diagnosis for ADHD. Treatment
      .initiation. was defined as a new prescription for an ADHD medication preceded by
      3 months without similar therapy. Two separate analyses were done, one comparing
      medication starts for ATX with those of any STIM, the other comparing starts of
      ATX with long-acting stimulants (LA-STIMs). Logistic regression analyses of prior
      year administrative claims were used to compare the frequencies of differential
      predictors of the use of medication. RESULTS: There were 10,359 patients aged >18
      years who initiated ATX or a STIM between April and December of 2003 and had at
      least 1 claim with a diagnosis for ADHD (International Classification of
      Diseases, Ninth Revision, Clinical Modification codes 314.0x). Approximately one
      third (28 of 82) of the comparisons related to patient demographics, diagnostic
      history, and previous treatment history was found to be related to the use of ATX
      versus STIMs and/or LA-STIMs. Patients were more likely to have received ATX than
      a STIM if they had prior diagnoses of bipolar disorder (odds ratio [OR] 1.47; 95%
      confidence interval [CI], 1.16-1.87), alcohol dependence (OR 1.80; 95% CI, 1.26
      2.58), anxiety (OR 1.21; 95% CI, 1.05-1.40), previous use of antipsychotic
      medication (OR 1.55; 95% CI, 1.22-1.96), or previous antidepressant use (OR 1.14;
      95% CI, 1.01-1.28). Prior use of behavioral services greater than 12 visits was
      associated with the use of ATX relative to STIMs (OR 1.46; 95% CI, 1.20-1.77) but
      not for ATX relative to LA-STIMs. Conversely, ATX was used less often than STIMs
      for initiation in younger adults aged 18 to 24 years (OR 0.66; 95% CI, 0.58
      0.74), female patients (OR 0.89, 95% CI, 0.80-0.99), patients with personality
      disorders (OR 0.53; 95% CI, 0.34-0.82), and those with prior use of STIMs (OR
      0.62; 95% CI, 0.56-0.69). The majority of comparisons (54 of 82) related to
      demographics, diagnostic history, and previous treatment history did not show
      statistically significant associations. CONCLUSIONS: During the first year of
      ATX.s market introduction, some differences in the frequency of various clinical
      factors were found in adults treated with ATX compared with those patients who
      received STIMs. This association may suggest that STIMs and ATX are used to
      address different treatment needs in adults with ADHD. Future studies will need
      to determine the significance of the practice pattern differences inferred here
      and if they persist after ATX has been on the market longer.

PMID- 16623608
TI  - Relationship of blood pressure control to adherence with antihypertensive
      monotherapy in 13 managed care organizations.
AB  - OBJECTIVE: This study was conducted to evaluate the relationship between
      medication compliance and blood pressure (BP) control among members of 13 managed
      care organizations with essential hypertension (HTN) who received
      antihypertensive monotherapy for at least 3 pharmacy claims prior to the blood
      pressure measurement. METHODS: This was a retrospective review of medical and
      pharmacy claims over a 4-year period (1999-2002) from 13 U.S. health plans. Data
      were collected by trained health professionals from randomly selected patient
      medical records per Health Plan Employer Data and Information Set (HEDIS)
      technical specifications. Patients were selected if they (1) had received
      monotherapy or fixed-dose combination therapy (administered in one tablet or
      capsule) during the time BP was measured (thus those with no BP drug therapy were
      excluded); (2) had received 3 or more antihypertensive pharmacy claims for the
      antihypertensive drug therapy prior to BP measurement; and (3) had one or more
      antihypertensive pharmacy claims after BP was measured. Control of BP was defined
      according to guidelines of the Sixth Report of the Joint National Committee (JNC
      6) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure
      (<140/90 mm Hg, or <130/85 mm Hg for patients with diabetes). Medication
      adherence was measured using the medication possession ratio (MPR), and MPR was
      used to classify patients into 3 adherence levels: high (80%-100%), medium (50%
      79%), and low (<50%). The relationship between medication adherence and BP
      control was assessed using a logistic regression model. RESULTS: There were
      1,017,181 patients with a diagnosis of HTN in medical claims data from which
      10,734 (10.6%) were randomly selected for chart review. There were 1,032 patients
      (9.6%) in the sample who had a diagnosis of HTN but who were excluded because
      they had no HTN drug therapy. Of the total 9,894 patients (92.2%) who were
      excluded from the sample, 3,029 patients (28.2%) met all other inclusion criteria
      but were receiving more than one HTN drug. Of the 840 patients on HTN
      monotherapy, the mean age was 59 12.2 years; 422 (50%) were women, 16% had
      diabetes, and 43% had dyslipidemia. The monotherapy HTN drug was an angiotensin
      converting enzyme inhibitor (27% of patients), calcium channel blocker (22%),
      beta-blocker (20%), or diuretic (11%). Of the 840 patients, 629 (74.8%) were
      determined to have high medication adherence, 165 (19.6%) had medium adherence,
      and 46 (5.5%) had low adherence. Approximately 270 (43%) of high adherence
      patients achieved BP control compared with 56 (34%) and 15 (33%) patients with
      medium and low adherence, respectively. High-adherence patients were 45% more
      likely to achieve BP control than those with medium or low compliance after
      controlling for age, gender, and comorbidities (odds ratio=1.45; P =0.026).
      CONCLUSION: These results demonstrate that 75% of these health plan members with
      a diagnosis of essential HTN who were selected for receipt of at least 4 pharmacy
      claims for HTN monotherapy exhibited high medication adherence. However, only 43%
      of high-adherence patients attained their target (JNC 6) blood pressure goal
      compared with 33% to 34% of patients with medium or low adherence to
      antihypertensive monotherapy.

PMID- 16623609
TI  - Assessment of clinical, service, and cost outcomes of a conversion program of
      sumatriptan to rizatriptan ODT in primary care patients with migraine headaches.
AB  - OBJECTIVE: Managed care organizations can increase the value of drug therapy by
      negotiating discounts on drug acquisition costs with pharmaceutical manufacturers
      and promoting use of preferred drugs, including the conversion of patients to
      preferred medications. This investigation was designed to assess conversion
      success, migraine drug utilizations, and patient satisfaction with a clinical
      pharmacist-managed conversion program from sumatriptan to rizatriptan ODT, both
      formulary drugs. METHODS: This was a retrospective cohort study conducted in a
      managed care organization for patients aged 18 years or older who had picked up
      at least one outpatient prescription for any sumatriptan dosage form at the
      pharmacy between January 2002 and June 2002. Patients. pharmacy and medical data
      were reviewed to assess eligibility (e.g., no history of rizatriptan failure) for
      conversion from sumatriptan to rizatriptan orally disintegrating tablet (ODT).
      There was no copayment difference for members for rizatriptan ODT versus
      sumatriptan. A questionnaire was developed to assess 2 domains: (1) patient
      satisfaction with the medication conversion process and (2) preference for
      rizatriptan ODT or sumatriptan. A random sample of 315 patients who initiated
      conversion to rizatriptan ODT was surveyed. Electronic pharmacy claims were
      reviewed to determine the number of patients who were successfully converted from
      sumatriptan to rizatriptan ODT. Pharmacy expenditures and total health care
      utilization and expenditures in the 180 days prior to (baseline) and after the
      conversion (followup) to rizatriptan ODT were compared for the cohorts of
      subjects who were successfully converted and those patients who were not
      successfully converted. RESULTS: Therapeutic conversion from sumatriptan to
      rizatriptan ODT was attempted in 457 patients; 214 (47%) were successfully
      converted. The only difference between the 2 cohorts at baseline for the 6 months
      prior to attempted conversion was a higher mean number of sumatriptan doses per
      patient per month (PPPM) in the 243 failed conversions (mean 3.5, SD 2.9)
      compared with the 214 successful conversions (mean 2.8, SD 2.8, P =0.003). The
      median triptan doses increased by 1.0 PPPM in both cohorts (P =0.882), from 2.0
      to 3.0 doses PPPM in the group of successful conversions and from 2.7 to 4.0 in
      the group of unsuccessful conversions. The survey response rate was 55% for both
      successful and for unsuccessful conversions. More than 90% of the patients in
      both cohorts were satisfied with the level of care provided by the clinical
      pharmacy staff during medication conversion, and there was no difference between
      the 2 cohorts in patient satisfaction (P=0.761). Rizatriptan ODT was preferred by
      68.0% and 8.5% of successful and failed conversion subjects, respectively (P
      <0.001). Using representative group purchase prices, triptan expenditures for
      successful conversion subjects were reduced by a median of -2 dollars (6 %) PPPM
      while triptan expenditures for unsuccessful conversions increased by a median of
      8 dollars (P <0.001). There were no differences for either cohort in median PPPM
      changes in migraine-related office visits (0.0 median change in office visits, P
      =0.748) or office-visit costs (0 dollars median change, P =0.861) for
      preconversion versus postconversion attempts Regression modeling identified that
      lower total counts of sumatriptan doses filled during baseline period was an
      independent predictor of successful conversion to rizatriptan ODT (P <0.001).
      There was an average of 3.5 triptan medication fills per patient for successful
      conversion during the 6-month follow-up period, with 78% of these subjects
      filling at least 2 prescriptions for rizatriptan ODT during this period.
      CONCLUSIONS: This conversion program for sumatriptan to rizatriptan ODT was
      successful in converting almost half of primary care patients to the preferred
      product despite the absence of a copayment incentive for members to agree to the
      conversion. There were no measurable medical or economic consequences of the
      conversion, and patient satisfaction with the quality of care was maintained.
      Future efforts are likely to have a higher success rate if focused on converting
      patients with less-severe migraine headaches, as measured by the need for
      baseline rescue medication, since lower acuity was the only independent predictor
      of successful conversion in this conversion program for 2 triptan drugs.

PMID- 16623610
TI  - Adherence to the NASPE guideline for amiodarone monitoring at a medical
      university.
AB  - OBJECTIVE: Amiodarone is an effective antiarrhythmic, but the clinical usefulness
      of this agent is complicated by its extensive side-effect profile, which
      necessitates careful patient selection and frequent monitoring. The purpose of
      this study was to quantify adherence to published recommendations for baseline
      monitoring when initiating inpatient amiodarone therapy at a university teaching
      hospital and determine whether appropriate serial monitoring of chronic
      amiodarone therapy (>or= 6 months) is occurring in the outpatient setting.
      METHODS: A retrospective review of electronic medical records was conducted for
      inpatients at the Medical University of South Carolina (MUSC) who received
      amiodarone between November 1, 2003, and March 31, 2004, and for a subset of
      outpatients who had received amiodarone therapy for at least 6 months. Their
      medical records were reviewed for demographic data; reason for, date of
      initiation of, and duration of amiodarone therapy; and the occurrence of
      laboratory and diagnostic tests. The amiodarone guideline from the North American
      Society of Pacing and Electrophysiology (NASPE) was used as the measure of
      appropriate monitoring for baseline and follow-up chest x-rays (CXRs), liver
      function tests (LFTs), thyroid function tests (TFTs), and pulmonary function
      tests (PFTs). RESULTS: Over the 5-month period from November 1, 2003, through
      March 31, 2004, 277 adult patients received oral amiodarone as inpatients at
      MUSC. Of these, 45 patients (16%) were initiated on chronic amiodarone therapy
      during their hospital admission. Baseline assessments of CXRs, LFTs, and TFTs
      occurred in 82% to 87% of these patients. Baseline assessment of PFTs occurred in
      24% of patients, and 55% of these assessments included a diffusion capacity
      (DLCO). Overall, only 5 (11%) of the 45 patients initiated on amiodarone received
      all recommended monitoring tests. Twenty patients with available outpatient
      records in the MUSC system were identified as receiving chronic amiodarone
      therapy. Baseline assessments of LFTs, TFTs, and CXRs occurred in approximately
      75% to 95% of these patients; baseline assessment of PFTs occurred in <or= 30%,
      and 83% of these included a DLCO. Chronic monitoring at recommended time
      intervals for LFTs and TFTs occurred in 35% and 20% of patients, respectively,
      whereas annual CXRs were performed appropriately in 50% of patients. CONCLUSION:
      Our data suggest that opportunities exist for improved monitoring of amiodarone
      therapy according to the NASPE guidelines and provide support for the development
      of a protocol to ensure continuous amiodarone monitoring.

PMID- 16623611
TI  - Case report: lack of control of diabetes and weight gain in a patient on
      initiation and rechallenge of therapy with olanzapine.
AB  - The following is a case report analysis intended to draw attention to the need
      for better care coordination by describing the observed relationship of
      olanzapine to metabolic changes manifested as uncontrolled diabetes mellitus and
      weight gain. A 47-year-old male with bipolar I disorder/hallucinations presented
      to the Veterans Affairs Medical Center (VAMC) with suicidal ideations. He was
      referred to the psychiatry service where he was treated with olanzapine. He was
      followed exclusively by the psychiatry service for more than a year. During that
      time,weight issues and diabetes status were not addressed. Upon presenting to the
      primary care service a year and a half later, the patient was taking 40 mg per
      day of olanzapine and had gained 62 pounds, a 30% increase in body weight;
      glycosylated hemoglobin (A1c) was 11.1%. The patient was enrolled in a weight
      loss clinic, and his diabetes medications were adjusted.Subsequently, olanzapine
      was discontinued because of weight gain and uncontrolled diabetes. Blood sugar
      and A1c were finally stabilized one month after discontinuation of olanzapine
      (A1c,6.9%). The patient experienced a relapse in his bipolar disorder,and
      olanzapine was restarted at 20 to 40 mg per day. His blood sugar became
      uncontrolled, he gained 13 pounds, and his A1c increased to 9.4%.

PMID- 16623612
TI  - Timeline and potential impact of CMS's drug competitive acquisition program
      (CAP).

PMID- 16623613
TI  - Relative value of the NSAIDs, including COX-2 inhibitors and meloxicam.

PMID- 16623614
TI  - Step therapy is not appropriate for antiepileptic drugs.

PMID- 16623616
TI  - Sound medication therapy management programs.

PMID- 16623617
TI  - Comparison of stroke among Christians and Muslims in Thrace, Greece.
AB  - INTRODUCTION:  BACKGROUND AND PURPOSE: Previous studies have demonstrated
      significant racial differences in incidence, age of onset, outcome and subsequent
      risk factors of stroke. However, there is scarce evidence available for Muslim
      populations worldwide. Xanthi region, a mainly rural and remote area in northern
      Greece, which is characterized by a mixed Christian/Muslim population, is
      considered appropriate for further studies in this area. METHODS: A prospective
      clinical study, based on a cohort of 530 consecutive unselected patients, 366
      Christians and 164 Muslims, who had their first documented episode of stroke
      between 1998 and 2002. Chi-square and Fisher's exact test for comparison between
      discrete parameters, Student's t-test for comparison between quantitative
      parameters and Pearson's r for correlations (along with Bonferroni's adjustment)
      were used. A multiple logistic regression model was performed for evaluation of
      religion and gender as independent predictors of type of stroke. RESULTS:
      Muslims, when compared with Christians: (1) present with ischemic stroke less
      often (p = 0.049); (2) suffer from stroke at a younger age (67.26 +/- 9.77 vs
      71.43 +/- 10.88 years; p < 0.001); (3) show a significantly lower incidence rate
      (87.2 vs 173.9 cases/100,000 person*years; RR 1.994; p < 0.001); (4) have lower
      rates of diabetes (p = 0.019) and atrial fibrillation (p < 0.001) and (5) present
      similar mortality (p = 0.347). CONCLUSIONS: Lower diabetes and atrial
      fibrillation rates among the Muslims of Thrace, Greece, might account for their
      low incidence of stroke. The contribution of culture-related habits (diet,
      occupation) remains to be investigated in further studies.

PMID- 16623618
TI  - Rural health's demographic destiny.
AB  - Demography is the study of the size and composition of populations. Populations
      change size through births, deaths and net-migration. Over time, mortality,
      fertility and migration patterns create populations that may be large or small,
      young or old, growing or declining. Rural and remote Australia has a unique
      demography that determines its health problems and health service needs. The
      tendency of young adults to leave rural and remote areas for cities means that
      they leave behind communities which are, on average, older than those found in
      the cities. Rural and remote women have slightly more children at significantly
      younger ages, but because of out-migration, the actual number of babies born
      outside of the cities is smaller than would be expected. Most rural and remote
      areas already have a high proportion of their population over 65 years old. Many
      communities with an older population are declining in absolute numbers but the
      need for health services may be greater than required for smaller, younger
      communities. In contrast to the trends in total population, the rural and remote
      Aboriginal and Torres Strait Islander population is growing rapidly. This is the
      result of a higher proportion of young people, higher fertility rates and lower
      rates of moving to cities. The health characteristics of rural and remote
      Australia increasingly reflects the higher morbidity of Indigenous and older
      people. Responding to this demographic destiny is the present and future
      challenge.

PMID- 16623619
TI  - Academic performance and scientific involvement of final year medical students
      coming from urban and rural backgrounds.
AB  - INTRODUCTION: The aim of this study was to evaluate the academic performance and
      research involvement of students coming from urban and rural backgrounds. To our
      knowledge, this is the first such study of undergraduate medical students in
      Croatia. METHOD: We surveyed the final (sixth) year medical students from Medical
      School, University of Zagreb, Croatia. Students were surveyed during the academic
      year 2004/2005, several months prior to their graduation. We analysed students'
      academic performance (grade point average, which is the most important academic
      success indicator in Croatia, and the number of failed study years) and research
      involvement (involvement in research projects and the possible subsequent
      publication of scientific articles). Additionally, we investigated the extent of
      extracurricular activities, and students' workplace preferences. Data were
      analysed using chi2 test, Fisher's exact test, and Kruskal-Wallis test, due to
      non-normal data distribution. RESULTS: A total of 204 students (out of 240
      enrolled, with a response rate of 85%) were surveyed, and divided into three
      groups: (1) those coming from the highly urbanised background (capital and other
      highly urbanised areas; n = 100, 49%); (2) mid-urban (towns; n = 75, 37%); and
      (3) rural and remote backgrounds (n = 29, 14%). There was no indication of gender
      gap or age difference among the three groups. However, significant differences
      were recorded in most academic and research indicators. Students from highly
      urbanised backgrounds reported the best grade point average (p = 0.022). Students
      from rural and remote backgrounds most commonly reported a study year failure (p
      = 0.032), with 17 (59%) cases, compared with 32 (32%) and 31 (42%) cases in high
      and mid-urban ones, respectively. Rural and remote students were also the most
      likely to experience multiple years failure (p = 0.030), were the least often
      involved in research projects (p = 0.002), and reported the least interest in
      career supplemented with scientific research (p = 0.015). Finally, students from
      rural and remote backgrounds were the least commonly involved in extracurricular
      activities, such as membership in student organizations (p = 0.005), or various
      hobbies (p = 0.009). However, 12 (41%) of rural and remote students were likely
      to seek employment in rural and remote areas, compared with a much lower percent
      among high and mid-urban students, with 16 (16%) and 16 (21%) students,
      respectively (p = 0.014). CONCLUSION: This study exhibited significant
      differences in the academic performance and research involvement of students
      coming from urban and rural backgrounds. Students from highly urbanised
      background reported the best academic indicators, while students from rural and
      remote backgrounds reported the poorest. Implementation of a rural students'
      support program should be strategically planned and carried out, because students
      from rural backgrounds in more than half the cases experienced a study year
      failure. Because students from rural and remote backgrounds were the most likely
      to prefer employment in rural and remote areas, they present a valuable resource
      for reduction of disparities in health workforce geographical distribution.

PMID- 16623620
TI  - Emergence of amphotericin B-resistant Cryptococcus laurentii meningoencephalitis
      shortly after treatment for Cryptococcus neoformans meningitis in a patient with
      AIDS.
AB  - A unique occurrence of two subsequent episodes of HIV-associated Cryptococcus
      neoformans followed by C. laurentii meningoencephalitis (successfully cured with
      fluconazole after demonstrated amphotericin B resistance) is presented and
      discussed. The available literature reported only two cases of HIV-associated C.
      laurentii infection to date, while a concurrent infection by C. neoformans and C.
      laurentii has been reported only once in a patient without HIV disease. The
      absence of prior descriptions of documented central nervous system infection by
      C. laurentii in non-HIV-infected patients is emphasized as well as the
      unpredictable in vitro and in vivo antifungal susceptibility of this non
      neoformans Cryptococcus spp., and its apparent prevalence in hospitalized
      patients who received prior antifungal treatments. All epidemiologic, diagnostic,
      clinical, and therapeutic implications are discussed on the basis of the evolving
      characteristics of opportunism in the era of highly active antiretroviral therapy
      (HAART).

PMID- 16623621
TI  - Failure of modified directly observed therapy combined with therapeutic drug
      monitoring to enhance antiretroviral adherence in a patient with major
      depression.
AB  - Improving medication nonadherence in HIV-infected patients with concomitant
      psychiatric issues remains a challenging therapeutic dilemma. One strategy may be
      to use a short course of modified directly observed therapy combined with
      therapeutic drug monitoring as an adherence intervention. Individual drug
      pharmacokinetics could be evaluated while the increased visit frequency is an
      opportunity to provide additional patient training and psychosocial support. We
      report our experience with a 43-year-old woman with severe depressive symptoms
      and persistent virologic failure despite appropriate therapy. Although the
      intervention was well-received by the patient, improvements in medication
      adherence behaviors waned over time. It should be recognized that not all
      patients are capable of achieving lifelong medication adherence and may benefit
      from continued supervised therapy.

PMID- 16623622
TI  - Short-term safety and tolerability of didanosine combined with high- versus low
      dose tenofovir disproxil fumarate in ambulatory HIV-1-infected persons.
AB  - Coadministration of didanosine (ddI) and tenofovir (TDF) results in increased ddI
      serum concentrations, which may lead to increased risk of ddI-associated
      toxicities. To evaluate the safety and tolerability of ddI/TDF, we performed a
      retrospective cohort analysis of patients seen in the HIV Outpatient Study, an
      ongoing dynamic cohort study of HIV-infected persons in clinical care. Study
      subjects were those who received at least 14 days of combined ddI/TDF before
      October 2003. Of 260 subjects who received ddI/TDF-based antiretroviral therapy,
      155 (60%) received high-dose ddI (400 mg daily dose) and 105 (40%) received low
      dose ddI (100-250 mg daily). Forty-two of the high-dose ddI recipients were later
      switched to low-dose ddI. The median time of observation for those on high-dose
      ddI only was 5 months, high-dose ddI switched to low-dose ddI was 16 months, and
      low-dose ddI only was 5 months (p < 0.05). Discontinuations because of toxicity
      were more frequent on high-dose ddI regimens (34/155, 22%) than on low-dose ddI
      regimens (9/105, 9%) (unadjusted odds ratio [OR(unadj)] 3.0, 95% confidence
      interval [95% CI] 1.30-7.09; p = 0.007). Among subjects without preexisting
      peripheral neuropathy, 12 (12%) of 101 subjects ever on high-dose ddI regimens
      had treatment-emergent peripheral neuropathy compared to 2 (4%) of 55 subjects on
      low-dose ddI regimens (OR(unadj) 3.57; 95% CI, 0.72-24.1; p = 0.14). Among
      patients without a history of pancreatitis, 6 (4%) of 153 subjects developed
      pancreatitis after starting high-dose ddI regimens, compared to none of the 103
      subjects on low-dose ddI regimens (OR(adj) and 95% CIs undefined; p = 0.08).
      Severe laboratory abnormalities of creatinine, phosphorous, and bicarbonate were
      not different between the groups. A summary variable for any event-
      discontinuation for toxicity, treatment- emergent adverse event or abnormal
      laboratory values--indicated that 44 (28%) of 155 of those on high-dose ddI
      versus 13 (12%) of 105 on low-dose ddI developed any event (OR(unadj) 2.81; 95%
      CI, 1.36-5.86; p = 0.004). In conclusion, high-dose ddI/TDF-based therapy was
      more frequently associated with drug-related toxicity, adverse events, and
      treatment discontinuation than low-dose ddI/TDF regimens; low-dose ddI with TDF
      was generally well tolerated in these HIV-infected persons.

PMID- 16623623
TI  - Longitudinal trends in antiretroviral use in a cohort of men and women in
      Ontario, Canada.
AB  - Initial studies have shown impaired access to antiretrovirals and slower adoption
      of new therapies by women. It is unclear if similar treatment delays still occur,
      especially in those with a publicly funded health care system in Ontario, Canada.
      The objectives of this study were (1) to evaluate longitudinal patterns of
      antiretroviral use in patients with HIV in Ontario and (2) to determine if gender
      differences exist in access to and uptake of antiretroviral drugs over time. A
      retrospective medical chart review was undertaken. One hundred four HIV-positive
      patients were recruited from nine hospital-based HIV outpatient clinics
      throughout Ontario. From time of study enrollment in 1999-2001 to the first
      clinic visit (8.1 +/- 3.2 years; range, 2.3-16.8 years), CD4+ T-cell counts, date
      of and agents used in initial antiretroviral regimen, and first HAART regimen
      were evaluated by gender. Kaplan-Meier plots were used to evaluate time to drug
      initiation from known HIV diagnosis. Serial cross sections of numbers and types
      of antiretroviral drugs prescribed in March, June, September, and December 1988
      to 2001 were also compared as was number of regimens used. There were few
      differences between men and women in antiretroviral use; both initiated therapy
      within 2.2 +/- 2.3 years of HIV diagnosis at an average CD4 counts of 300.3 +/-
      150.1 cells per microliter. Antiretroviral treatment regimens changed over time,
      with limited variation by gender. In the period immediately surrounding the first
      highly active antiretroviral therapy (HAART) recommendations by the U.S.
      Department of Health and Human Services in July 1997, significantly more
      antiretroviral drugs were prescribed for men than women. Antiretroviral
      prescribing in patients attending hospital- based HIV outpatient programs in
      Ontario is consistent with antiretroviral treatment guidelines over time, without
      substantial differences in antiretroviral access and use by gender.

PMID- 16623624
TI  - Positive provider interactions, adherence self-efficacy, and adherence to
      antiretroviral medications among HIV-infected adults: A mediation model.
AB  - Adherence to antiretroviral (ARV) therapy for HIV infection is critical for
      maximum benefit from treatment and for the prevention of HIV-related
      complications. There is evidence that many factors determine medication
      adherence, including adherence self-efficacy (confidence in one's ability to
      adhere) and relations with health care providers. However, there are no studies
      that examine how these two factors relate to each other and their subsequent
      influence on HIV medication adherence. The goal of the current analysis was to
      explore a model of medication adherence in which the relationship between
      positive provider interactions and adherence is mediated by adherence self
      efficacy. Computerized self-administered and interviewer-administered self
      reported measures of medication adherence, demographic and treatment variables,
      provider interactions, and adherence self-efficacy were administered to 2765 HIV
      infected adults on ARV. Criteria for mediation were met, supporting a model in
      which adherence self-efficacy is the mechanism for the relationship between
      positive provider interactions and adherence. The finding was consistent when the
      sample was stratified by gender, race, injection drug use history, and whether
      the participant reported receipt of HIV specialty care. Positive provider
      interactions may foster greater adherence self-efficacy, which is associated with
      better adherence to medications. Results suggest implications for improving
      provider interactions in clinical care, and future directions for clarifying
      interrelationships among provider interactions, adherence self-efficacy, and
      medication adherence are supported.

PMID- 16623625
TI  - Paradoxical effects of clinician emphasis on adherence to combination
      antiretroviral therapy for HIV/AIDS.
AB  - Constructive relationships between clinicians and patients being treated for
      HIV/AIDS are critical to treatment success. Trust, caring, and expertise have all
      been cited as important components of such relationships. As-yet unexamined,
      however, is the impact of the urgency patients sense in their clinicians
      concerning proper adherence to antiretroviral medications. Qualitative interviews
      (total, 214) from a study of adherence to highly active antiretroviral therapy
      (HAART) for active illegal drug users (n = 52) provided data for the analysis.
      Among other topics, interviews examined patients' perspectives on relationships
      with their providers. Study participants experienced their physicians as
      insisting on perfect adherence. Fearing disapproval if they disclosed missing
      doses, interviewees chose instead to conceal adherence information. Apprehensions
      about failing at perfect adherence led some to cease taking antiretrovirals over
      the course of the study. Well-intentioned efforts by clinicians to emphasize the
      importance of adherence can paradoxically undermine the very behavior they are
      intended to promote. Adherence can be approached in ways that inspire honesty and
      openness and build trust in the treatment relationship, laying the groundwork for
      a collaborative approach to solving problems in taking antiretroviral medications
      as prescribed.

PMID- 16623626
TI  - Multidisciplinary, inpatient directly observed therapy for HIV-1-infected
      children and adolescents failing HAART: A retrospective study.
AB  - Children and adolescents with HIV-1 infection and elevated viral loads are at
      risk for disease progression. When outpatient adherence efforts fail to reduce
      viral loads, we have chosen to hospitalize patients for directly observed
      antiretroviral therapy. A retrospective chart review was performed for patients
      who were admitted for adherence concerns to a rehabilitation facility from
      December 1, 2000 to December 1, 2003. Differences in CD4 count and viral load at
      admission, prior to discharge and 6 months after discharge were evaluated using
      the Wilcoxon signed-ranks test. Nineteen admissions were included in the
      analysis. Compared to the mean CD4 count at admission (262), the mean CD4 counts
      at discharge (492) and 6 months after discharge (429) were significantly higher
      (p < 0.001 and p = 0.01, respectively). Similar results were observed for change
      in CD4 percentage. Compared to the mean viral load at admission (log 5.7), the
      mean viral loads at discharge (log 4.7) and 6 months after discharge (log 5) were
      significantly lower (p < 0.001 and p < 0.004). The majority of admissions (74%)
      involved a change in highly active antiretroviral therapy (HAART) regimen. In
      conclusion, hospitalization for directly observed therapy of HIV-1-infected
      children and adolescents with elevated viral loads and nonadherence resulted in
      an immediate and sustained (up to 6 months) reduction in viral load and increase
      in CD4 count.

PMID- 16623627
TI  - HIV/AIDS risk factor ascertainment: A critical challenge.
AB  - Ascertainment of risk factors for HIV transmission is critical to monitoring the
      HIV epidemic. Since 1993, there has been an increase in the proportion of
      HIV/AIDS cases that are reported to the Centers for Disease Control and
      Prevention (CDC) without an identified risk factor for HIV. About this time many
      areas implemented laboratory reporting, which generates an initial report with
      little to no HIV risk factor information. In 2001, the CDC convened a group of
      experts who recommended changes to the presentation of HIV risk factor data. The
      CDC subsequently funded two projects to improve the collection of HIV risk
      factors by surveillance staff. Since 2004, the CDC and state surveillance
      coordinators revised surveillance guidance to recommend prioritization of follow
      up and provider training, and to monitor key variables while providing feedback
      to reporters. The CDC also began an evaluation of provider-targeted educational
      materials. The CDC has also been working with professional associations to
      incorporate methods for documenting HIV risk factors into existing training
      modules. CDC and state surveillance coordinators will need to continue efforts to
      educate, train, and identify barriers for providers in order to improve the
      completeness of HIV risk factor documentation and reporting.

PMID- 16623628
TI  - Theoretical and methodological issues in conducting research related to health
      care utilization among individuals with HIV infection.
AB  - Although empirical information on resource use during HIV infection is vital to
      improving quality of care, the issues involved in conducting research on resource
      use have received little attention in the medical literature. The purpose of this
      paper is to review the theoretical and methodological issues of conducting
      research on health care utilization patterns among persons with HIV/AIDS.
      Conceptual definitions of utilization are compared and contrasted. Three
      theoretical frameworks, the Andersen Behavioral Model, the Health Belief Model,
      and the Biopsychosocial Model are described to illustrate their applicability in
      future research studies. Research designs, measurement considerations, sampling
      approaches, and existing data sources on utilization are reviewed.
      Recommendations for health care utilization research are summarized and highlight
      the importance of designing studies and generating data for investigation of the
      factors facilitating patients' use of an optimal array of services including
      prevention, long-term, and rehabilitation care.

PMID- 16623631
TI  - Molecular evidence of HTLV-II subtype B among an urban population living in South
      Brazil.
AB  - Human T cell lymphotropic virus type II (HTLV-II) is a deltaretrovirus endemic in
      Indian populations living in Central and South America, among Pygmies tribes from
      Central Africa, and epidemic among injecting drug users (IDUs) in the United
      States, Europe, Southeast Asia, and South America. To date only the HTLV-IIa
      subtype has been demonstrated among Brazilians (Amazon basin Indians, blood
      donors, and IDUs). We analyzed HTLV-II isolates from 12 individuals living in the
      urban area of Porto Alegre, Southern Brazil, identified as seropositive for
      HTLVI/II in a blood donation. The HTLV-II long terminal repeat (LTR) region was
      sequenced and compared with nucleotide sequences of isolates HTLV-IIa (Mo), HTLV
      IIb (NRA) prototypes. Phylogenetic analysis of the LTR region demonstrated that
      seven new isolates clustered together with American Indians HTLV-IIb isolates,
      and five new HTLV-IIa isolates clustered within the HTLV-IIa Brazilian subgroup,
      named the HTLV-IIc subtype. Both HTLV-IIa and IIb seem to be endemic in the urban
      area of Porto Alegre, South of Brazil, and could have reached this region via the
      Amazon basin and the Pacific Coast ancient human migratory pathways. To our
      knowledge this is the first study demonstrating the presence of HTLV-IIb among
      the urban population in Brazil.

PMID- 16623632
TI  - Structured intermittent interruption of chronic HIV infection treatment with
      highly active antiretroviral therapy: effects on leptin and TNF-alpha.
AB  - The changes in nutritional parameters and adipocytokines after structured
      intermittent interruption of highly active antiretroviral treatment of patients
      with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV
      infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of
      structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the
      beginning of structured interruptions <50 copies/ml; median time of previous
      treatment: 60 months) were evaluated during three cycles of intermittent
      interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral
      load, anthropometric measures, and serum concentrations of triglycerides,
      cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II
      were determined. After the three cycles of intermittent interruptions of therapy,
      no significant differences in CD4+ T cell count/microl, viral load, or serum
      concentrations of cholesterol or triglycerides with reference to baseline values
      were found. A near-significant higher fatty mass (skinfold thicknesses, at the
      end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant
      increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a
      decrease in serum concentrations of soluble receptors of tumor necrosis factor
      (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were
      detected. Structured intermittent interruption of highly active antiretroviral
      treatment of patients with chronic HIV infection induces a valuable positive
      modification in markers of lipid turnover and adipose tissue mass.

PMID- 16623633
TI  - Efficacy and safety of pegylated interferon-alpha2b plus ribavirin for the
      treatment of chronic hepatitis C in HIV-infected patients.
AB  - Low response rates and concerns about safety have limited the implementation of
      treatment for chronic hepatitis C (CHC) in patients with HIV infection. The
      efficacy and safety of pegylated interferon (peg-IFN) plus ribavirin in HIV
      infected patients with CHC were evaluated in a prospective, open-label,
      multicenter study. Sixty patients with persistently high transaminases, positive
      HCV-RNA, CD4 count > or = 300 cells/microl, and HIVRNA <10,000 copies/ml were
      included. Patients were given peg-IFN 80-150 microg/week plus ribavirin 800-1200
      mg/day. Treatment was scheduled for 24 weeks for genotypes 2/3 and 48 weeks for
      genotypes 1/4. In an intent- to-treat analysis, 16 (26.7%) patients achieved a
      sustained virological response (SVR). Twenty patients (33.3%) discontinued
      treatment prematurely, but only in 10 (16.6%) was discontinuation due to adverse
      events. Negative predictive values for SVR on the basis of HCV-RNA decline
      between baseline and week 4 were 100% for 1- and 2-log10 fall, and positive
      predictive values were 40% and 58.3% for 1- and 2-log10 fall, respectively. CD4
      fell by a median of 216 cells during treatment, but no HIV-associated
      complications occurred. In conclusion, treatment with peg-IFN alpha-2b plus
      ribavirin is safe and clears RNA-HCV in about one-quarter of HIV-infected
      patients with CHC. Efforts should be focused on optimizing management of side
      effects and counseling to improve adherence and to keep patients on treatment.
      Assessment of HCV-RNA at week 4 may help guide early therapeutic decision making.

PMID- 16623634
TI  - Long-term safety and efficacy of nevirapine-based approaches in HIV type 1
      infected patients.
AB  - Using a multicenter, cross-sectional, observation study, the long-term safety,
      metabolic profile, and viral efficacy of nevirapine (NVP)-based approaches in HIV
      1-infected patients treated for at least 2 years were assessed. For 4 months, all
      consecutive HIV-1-infected patients who had been receiving an NVP-containing
      regimen for at least 2 years were recruited. A total of 613 patients were
      included with a median follow-up period of 43 months (IQR: 31-51). At baseline,
      24.5% (150 patients) were treatment naive, 41.5% (254 patients) switched for
      simplification purposes, and 34% (209 patients) were failing HAART. Increases by
      five times or more in AST/ALT values were observed in fewer than 2% of patients.
      Only 5.7% of all adverse events reported during the investigation were
      attributable to NVP. The percentage of patients with normal HDL cholesterol
      levels rose from 17.7% at baseline to 35.4% at the last visit. At the latest time
      point available for analysis, 76% of naive and 74% of those who had switched had
      HIV-1 RNA loads of <50 copies/ml, while 59% of salvage patients achieved this
      level of viral suppression. Factors associated with viral suppression at the
      latest visit were adequate adherence (OR: 2.58, 95% CI: 0.85-7.78, p < 0.001),
      first-line treatment (OR: 3.02, 95% CI: 1.52-6.00, p = 0.002), and baseline CD4
      cells >400 cells/microl (OR: 2.34, 95% CI: 1.22-4.47, p = 0.010). Exposure to
      nevirapine for up to 4 years is safe. Liver toxicity is infrequent and generally
      mild. HDL cholesterol levels consistently increase over time and viral
      suppression is maintained.

PMID- 16623635
TI  - CD8 T cell response to Nef peptides and HIV type 1 control in early-treated
      patients after antiretroviral treatment interruption.

PMID- 16623637
TI  - Nonnucleoside reverse transcriptase inhibitor fold change or plasma concentration
      as a predictor of virological response over 48 weeks in highly treatment
      experienced HIV-positive individuals.
AB  - The nonnucleoside reverse transcriptase inhibitors (NNRTI) have low genetic
      barriers to resistance. Resistance can sometimes be overcome by increasing drug
      exposure. We assessed factors associated with 48-week virological response in
      treatment-experienced individuals receiving NNRTI therapy including resistance
      testing results and plasma drug exposure. Of 62 individuals assigned a new NNRTI
      based regimen following resistance testing therapy consisted of efavirenz in 35
      (56%) and nevirapine in 27 (44%) individuals. NNRTI fold change (FC) was
      determined from resistance test at baseline and plasma drug concentration at week
      4. Mean time weighted change from baseline VL was -0.68 log over 48 weeks.
      Significant associations with change from baseline VL included baseline VL and FC
      whereas plasma drug concentration was not associated. In this cohort of highly
      treatment-experienced individuals treated with NNRTI regimens, we did not observe
      a significant association between NNRTI plasma concentration and virological
      response.

PMID- 16623636
TI  - Higher risk of hyperglycemia in HIV-infected patients treated with didanosine
      plus tenofovir.
AB  - The combination of didanosine (ddI) and tenofovir (TDF) has potential advantages,
      but because of several pitfalls (unexpected decreases in CD4+ T cells, increased
      risk of pancreatitis) its use has been questioned. Since anecdotal cases of
      transient insulin-dependent diabetes mellitus were seen in our clinic in patients
      on ddI + TDF-containing regimens, we explored the rate of this complication in
      more detail. Retrospective analysis of plasma glucose levels in patients who
      completed 12 months of treatment with three different triple antiretroviral
      regimens including ddI + TDF, TDF, or ddI was done. Patients taking antidiabetic
      drugs and/or those with baseline glucose levels >125 mg/dl were excluded. Weight,
      age, concomitant antiretrovirals, and ddI dose were assessed. At 12 months
      without treatment changes, fasting glucose levels were compared to baseline. A
      multivariate analysis was performed to evaluate which variables were associated
      with glucose elevations. A total of 177 HIV-infected patients were assessed (78
      on ddI + TDF, 42 on TDF, and 57 on ddI). Mean baseline features were well
      balanced between groups for age (mean, 39 years), gender (78% male), CD4+ count
      (mean, 507 cells/mm3), weight (mean, 67 kg), and glucose level (mean, 95 mg/dl).
      There were only significant differences between groups for baseline viral load
      and protease inhibitor (PI) use (13% in the ddI + TDF arm vs. 7% and 9% in the
      TDF and ddI arms, respectively). At 12 months, 60% of the patients in the ddI +
      TDF arm were taking ddI 250 mg/day and the rest were on ddI 400 mg/day. At 12
      months, hyperglycemia was significantly more frequent in the ddI + TDF arm (33%)
      when compared to patients on TDF or ddI separately (5% and 10%, respectively). In
      the multiple linear regression analysis, a lower weight (beta -0.35; 95% CI -0.67
      to -0.03; p = 0.033) and use of ddI + TDF (beta: 13.05; 95% CI: 0.2 to 26; p =
      0.047) were independently associated with a higher risk of developing
      hyperglycemia. The risk of hyperglycemia is increased in patients treated with
      ddI + TDF, particularly in those with lower weight. As high ddI exposure has been
      associated with endocrine pancreatic dysfunction and diabetes, ddI "overdosing"
      as result of concomitant TDF use and low weight might explain our findings. These
      results add a further note of caution to the use of TDF and ddI in combination.

PMID- 16623638
TI  - Construction and characterization of feline immunodeficiency virus proviral
      mutants that coexpress interferon gamma and green fluorescent protein.
AB  - Vif deletion mutants of the feline immunodeficiency virus (FIV) were designed to
      express either enhanced green fluorescent protein (EGFP) (FIVdeltavifATGgfp) or
      feline interferon-gamma (IFN-gamma) (FIVdeltavifATGgamma) by insertion of the
      nonviral gene into the deletion site of the viral vif gene. Two in-frame start
      codons within vif were mutated without altering the overlapping pol translation
      frame to enhance expression of inserted genes. Expression of EGFP and IFN-gamma
      from FIVdeltavifATGgfp and FIVdeltavifATGgamma proviruses, respectively, was
      confirmed by fluorescent microscopy and immunocytochemical assays, respectively.
      Replication of viruses generated from these proviruses was detectable but
      severely restricted when compared to that of wild-type (WT) FIV-pPPR. A previous
      study demonstrated induction of protection against homologous FIV challenge by
      vaccination of cats with an attenuated FIV-pPPRdeltavif proviral DNA vaccine
      (Lockridge K et al.: Virology 2000;273:67-79). Coexpression of IFN-gamma or other
      cytokines from this attenuated provirus provides the opportunity to evaluate the
      ability of an immunomodulator to enhance the safety and efficacy of an infectious
      attenuated DNA vaccine. Moreover, a vif-deleted FIV provirus that coexpresses a
      reporter gene such as EGFP may be used to examine the localization of vif mutant
      viruses in vivo.

PMID- 16623639
TI  - Estradiol negatively regulates HIV-LTR promoter activity in glial cells.
AB  - HIV-associated dementia results from neuronal loss and an alteration of neuronal
      function due to a loss of synapses. While HIV infection in astrocytes is limited,
      astrocytes exhibit a chronic nonproductive infection that can lead to the release
      of neurotoxic proteins. Additionally, infection can disrupt the normal
      neurotrophic role of astrocytes that results in neuronal death. Gonadal steroid
      hormones are known to act as trophic and protective factors in the brain under a
      variety of normal and pathological conditions. In the present study, to determine
      if estrogen plays a role in the ability of Tat to function as a transcriptional
      activator within astrocytes, we examined the effect of estrogen on regulation of
      viral transcription. We utilized an immortalized human astrocyte cell line (SVGA)
      stably transfected with a reporter plasmid containing the HIV-1IIIB LTR driving
      the chloramphenicol acetyltransferase (CAT) gene. The amount of transcriptional
      activity was measured by quantifying the amount of CAT produced. We determined
      that 17beta-estradiol treatment (1 nM) had no effect on basal LTR activity.
      Following transfection with a Tat-expressing plasmid, there was a 100-fold
      increase in CAT production. This induction was reduced by 40% in cells pretreated
      with 17beta-estradiol. 17beta- Estradiol only suppressed transcription stimulated
      by Tat. Furthermore, we determined that this effect was specific to 17beta
      estradiol and estrogen receptor agonists. This activity was limited to astrocytes
      as no effect was observed in a monocytic cell line. Finally, the mechanism of
      action did not involve an alteration in levels of Cdk9 or Cyclin T1 proteins
      necessary for Tat activation of the HIV-1 LTR. This study demonstrates a novel
      activity of 17beta-estradiol in glial cells that could play a role in the
      maintenance of neuronal health during HIV infection of the central nervous
      system.

PMID- 16623640
TI  - Susceptibility to antiretroviral drugs of CRF01_AE, CRF02_AG, and subtype C
      viruses from untreated patients of Africa and Asia: comparative genotypic and
      phenotypic data.
AB  - Non-B HIV-1 viruses are predominant in developing countries where access to
      antiretroviral drugs (ARVs) is progressively being intensified. It is important
      to obtain more data on the susceptibility of these viruses to available ARVs.
      CRF01_AE, CRF02_AG, and subtype C strains of HIV-1 obtained from untreated
      patients from Vietnam, Cote d'Ivoire, and India were analyzed for their in vitro
      susceptibility to NRTIs, NNRTIs, PIs, and an entry inhibitor (T-20) using a
      recombinant viral assay (PHENOSCRIPT). The corresponding viruses, which had been
      previously sequenced in reverse transcriptase (RT), protease (prot), plus
      envelope (env) C2/V3 genes and had therefore been fully characterized, were
      further sequenced in env HR1 + HR2 regions. CRF01_AE isolates are sensitive to
      NRTIs and NNRTIs with the exception of one isolate that exhibits a decreased
      susceptibility to NNRTIs associated with a I135T substitution in RT. CRF02_AG and
      subtype C viruses are sensitive to NRTIs and NNRTIs but some CRF02_AG isolates
      tend to be resistant to abacavir, potentially related to associated substitutions
      of RT at positions 123 (D123N) plus 135 (I135V). Whereas all but one CRF01_AE
      isolates are fully susceptible to PIs, some CRF02_AG and, more frequently, some
      subtype C isolates are resistant to atazanavir. The role of substitutions in prot
      at positions of secondary resistance mutations 20, 36, 63, and 82 is raised with
      a potentially crucial role of the V82I substitution. Finally, all viruses tested,
      regardless of the CRF or subtype, are fully susceptible to T-20.

PMID- 16623643
TI  - Immunotherapy for brain tumors: quo vadis?

PMID- 16623641
TI  - High diversity of HIV type 1 in Algeria.
AB  - We have sequenced different genes of HIV-1 strains from infected individuals
      recruited in various geographic parts of Algeria; phylogenetic trees were
      constructed yielding molecular characterization of these strains. Subtype B
      accounts for 56% of the samples studied and is therefore the predominant subtype,
      particularly in the north part of the country; but there is a high diversity of
      the virus including CRF02_AG, CRF06_cpx, CRF02/CRF06 interrecombinants, and
      different other intersubtype and/or inter-CRF recombinants. The prevalence of
      these non-B viruses increases in the south part of Algeria that borders sub
      Saharan African countries. The high diversity of HIV-1 in Algeria has
      implications for virological follow-up, resistance surveys, and vaccine design.

PMID- 16623644
TI  - Substance abuse and schizophrenia: which comes first?

PMID- 16623645
TI  - A review of the use of modafinil for attention-deficit hyperactivity disorder.
AB  - Modafinil (Provigil) is a novel wakefulness-promoting agent that has been shown
      to have greater efficacy than placebo in the treatment of attention-deficit
      hyperactivity disorder (ADHD) in children and adults. In particular, three large,
      drug-company sponsored trials of a film-coated formulation of modafinil
      (modafinil-ADHD; Sparlon) in children and adolescents with ADHD demonstrated
      consistent improvements in ADHD symptoms compared with placebo. Mean reductions
      in symptom ratings (measured using the ADHD-Rating Scale-IV school version
      questionnaire) ranged from 15.0 to 19.7 (7.3 to 10.1 for placebo). The most
      common adverse events were insomnia, headache and decreased appetite. Modafinil
      was generally well tolerated with most side effects considered mild to moderate
      in severity. Modafinil may have advantages over current therapies for ADHD in
      that it can be administered once daily and has fewer reinforcing properties than
      traditional stimulants. Modafinil could potentially be a valuable new treatment
      option for patients with ADHD. However, rigorous comparative studies with current
      first-line treatments for ADHD and longer-term independent studies are necessary
      before modafinil's role in the treatment of ADHD can be fully established.

PMID- 16623646
TI  - Music therapy in the treatment of multiple sclerosis: a comprehensive literature
      review.
AB  - Coping with multiple sclerosis symptoms still remains a challenge for each
      patient suffering from this chronic inflammatory disease. Therefore, patients
      often turn to using complementary and alternative medicine (CAM). In this review,
      the authors aimed to investigate the current state of literature of music therapy
      in the treatment of multiple sclerosis (MS). Medline, PubMed, Embase, AMED,
      CAMbase and the Music Therapy World Journal Index were searched for the terms MS
      and 'music therapy'. In addition, an internet search using Google Scholar was
      performed. The authors found seven case-reports/series and seven studies on music
      therapy for MS-patients. Both the case reports and studies presented here are
      pioneer work. Most of the studies are naturally predominated by the use of
      qualitative and uncontrolled research designs. Nevertheless, the results of the
      studies as well as the case reports demonstrate patients' improvement in the
      domains of self-acceptance, anxiety and depression. The results of the studies as
      well as the case reports define a sufficient basis for further music
      therapeutical work as they show a variety of psychosocial and emotional benefits
      for MS patients.

PMID- 16623647
TI  - Gene therapy for malignant glioma.
AB  - Glioblastoma multiforme represents the most common primary malignant tumor of the
      adult CNS. Unfortunately, the median survival after surgical intervention alone
      is less than 6 months and the addition of radiotherapy can extend this time to
      only 9 months. Consequently, efforts aimed at developing new therapies have
      focused on new treatment strategies that specifically target tumor cells and
      spare normal cells. One such modality, gene therapy, has shown promise in the
      spectrum of agents utilized against brain tumors. This review highlights the
      principles of gene therapy and discusses the results of recent clinical trials in
      which gene therapy has been employed against malignant brain tumors.

PMID- 16623648
TI  - New concepts in the treatment of brain tumors in very young children.
AB  - The treatment of brain tumors in infants (children <3 years of age) in the last
      15-20 years has been a special field of interest for clinical investigation and
      research, since infants affected by brain tumors are an ideal experimental group
      of patients. New treatment strategies (conventional, myeloablative and
      intraventricular chemotherapy) have been tested on these patients in an effort to
      avoid or delay conventional irradiation. The amazing amount of knowledge that has
      been acquired from neuropathological and biological studies, as well as from the
      first generation treatment baby protocols, which were designed between 1985 and
      2000, is now leading to a new approach whereby treatment strategies are tailored
      to the patient's clinicopathological features.

PMID- 16623649
TI  - Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy in
      the management of intracranial ependymoma.
AB  - Ependymoma accounts for 5-10% of all childhood CNS tumors and less than 5% of
      intracranial tumors in adults. Ependymomas typically have a sharp tumor-brain
      parenchyma interface and this characteristic lends itself well to stereotactic
      radiation delivery. Data on the use of stereotactic radiosurgery (SRS) and
      fractionated stereotactic radiotherapy (FSRT) for ependymoma in various settings
      have emerged over the past 10 years. SRS has been used in recurrent disease and
      as a boost after external beam radiation therapy. FSRT has been used in pediatric
      brain tumors and can potentially limit the long-term toxicities associated with
      radiation therapy by reducing the amount of normal brain parenchyma treated. Long
      term follow-up is needed to determine the long-term efficacy and toxicities
      associated with these treatment modalities.

PMID- 16623650
TI  - Immunotherapy of neuroblastoma: present, past and future.
AB  - Neuroblastoma is a neuroectodermal tumor of childhood with poor prognosis and low
      survival in patients with advanced-stage disease who respond to conventional
      therapies but unfortunately, often present relapse. Therefore, the search for
      novel therapeutic strategies is warranted and represents the objective of many
      investigators. Among the new, innovative approaches, immunotherapy has attracted
      much interest. However, until recently, little information was available about
      the immunogenicity of human neuroblastoma.

PMID- 16623651
TI  - Oligodendroglial tumors.
AB  - Oligodendroglial tumors represent approximately 4-7% of all gliomas; however, in
      some series the incidence has been reported to be as high as 10-20% because of
      improved histological appreciation and recently recognized molecular signatures.
      Oligodendroglial tumors are classified as being low-grade oligodendroglial
      tumors, high-grade anaplastic oligodendroglial tumors or mixed oligo-astrocytic
      tumors. The mixed tumors can again be low-grade or high-grade. The recent
      European Organization for Research and Treatment of Cancer and Radiation Therapy
      Oncology Group randomized trials have provided level 1 evidence regarding the
      best management of these tumors. This review provides an overview of
      oligodendroglial tumors and discusses contemporary and evolving treatment
      strategies.

PMID- 16623652
TI  - Electroencephalographic biofeedback for the treatment of attention-deficit
      hyperactivity disorder in childhood and adolescence.
AB  - Considerable scientific effort has been directed at developing effective
      treatments for attention-deficit hyperactivity disorder (ADHD). Among alternative
      treatment approaches, electroencephalographic (EEG) biofeedback has gained
      promising empirical support in recent years. Short-term effects were shown to be
      comparable to those of stimulant medication at the behavioral and
      neuropsychological level, leading to significant decreases of inattention,
      hyperactivity and impulsivity. In addition, EEG biofeedback results in
      concomitant improvement of neurophysiological patterns. EEG biofeedback may
      already be used within a multimodal setting, providing affected children and
      adolescents with a means of learning to counterbalance their ADHD symptoms
      without side effects. However, there is still a strong need for more empirically
      and methodologically sound evaluation studies.

PMID- 16623653
TI  - Therapeutic challenges of attention-deficit hyperactivity disorder with substance
      use disorders.
AB  - Attention-deficit hyperactivity disorder (ADHD), a common neuropsychiatric
      disorder of childhood, adolescence and adulthood, is frequently comorbid with
      substance use disorders (SUDs) in both adolescents and adults. This paper will
      provide an overview of the relationship between ADHD and SUDs and discuss the
      primary areas of therapeutic challenge in the treatment of individuals with
      comorbid ADHD and SUDs, including the diagnosis of ADHD in populations with SUDs,
      selecting appropriate agents for use and prevention of abuse and/or diversion of
      the therapeutic pharmacological agents used in ADHD treatment. The authors will
      also provide a discussion on the future of research and treatment in this area
      and key issues for clinicians.

PMID- 16623654
TI  - Long-term outcomes of stimulant medication in attention-deficit hyperactivity
      disorder.
AB  - The rate of prescribing of stimulant medication for the treatment of attention
      deficit hyperactivity disorder (ADHD) has been progressively increasing in
      countries such as the USA and Australia. In the short term, stimulant medication
      is effective in reducing the symptoms of ADHD and appears well tolerated with
      relatively minor side effects. In the long term, much of the benefit of stimulant
      medication disappears after medication is ceased. Studies have demonstrated only
      marginal improvements in adult outcomes following a period of treatment in
      childhood. This may be owing to the beneficial effects being masked by the
      variability of the condition, the developmental changes in symptomatology that
      happen with maturation and the substantial influence of social and environmental
      factors. Stimulant medication may give some protection against later substance
      abuse. Stimulant medication may slightly elevate the blood pressure and possibly
      increase susceptibility to seizures and to tics and Tourette syndrome. Starting
      treatment with stimulant medication is usually associated with weight loss and a
      transient slowing of the height velocity, although it is believed that most
      children catch up during puberty. No studies were found that listed strokes or
      heart attacks as potential or actual complications, although one individual from
      a group of normal controls died suddenly of cardiac arrest in adolescence. It
      would appear that the medical complications associated with amphetamine addiction
      are not relevant to the therapeutic use of stimulant medication in the treatment
      of ADHD, although there is limited information on extended periods of treatment
      lasting 10 years or more.

PMID- 16623655
TI  - Aspirin in the treatment of acute migraine attacks.
AB  - Acetylsalicylic acid (aspirin or ASA) has been used for many years as an
      analgesic, antipyretic and anti-inflammatory drug. In recent years, evidence for
      its effectiveness in migraine headache has been demonstrated in several clinical
      trials. The effervescent highly buffered preparation of aspirin was shown to be
      effective, safe and well tolerated compared with placebo or other treatment
      options. The effervescent aspirin preparation is at least as effective as the
      combination of aspirin plus metoclopramide, but has fewer side effects. This
      review summarizes and analyzes clinical data of aspirin in the treatment of acute
      migraine attacks with respect to the different galenic formulations.

PMID- 16623656
TI  - Epileptogenic drugs: a systematic review.
AB  - A wide range of substances, including drugs and illicit compounds, increase the
      risk of epileptic seizures. In this systematic review, the authors address the
      issue of the epileptogenic potential of marketed drugs, with the aims of
      providing criteria for the assessment of the cause-effect relationship between
      drug exposure and the risk of seizures; and to identify the compounds better
      fulfilling the requirements of an epileptogenic drug. Finding a correlation
      between drug exposure and occurrence of seizures does not necessarily establish a
      causal association. In light of the available evidence, even with these
      limitations, some conclusive remarks can be made on the epileptogenic potential
      of some active principles. Drugs with high epileptogenic potential include
      meperidine, sevoflurane, clozapine, phenothiazines and cyclosporine. Drugs with
      intermediate epileptogenic potential include propofol, maprotiline, tricyclic
      antidepressants and chlorambucil. Drugs with low epileptogenic potential include
      fluorquinolones, carbapenems, bupropion and iodinated contrast media. Drugs with
      minimal or inconclusive epileptogenic potential include interferon alpha.

PMID- 16623657
TI  - Cognitive compromise in bipolar disorder with chronic cannabis use: cause or
      consequence?
AB  - This article briefly reviews the neuropsychological deficits associated with
      bipolar disorder and examines how substance abuse, in particular chronic cannabis
      use, may contribute to these. The focus of the article is cannabis, owing to its
      popularity in patients with bipolar disorder, although many studies focus on its
      use in conjunction with other substances. The findings are contextualized within
      bipolar disorder, examining functional outcome.

PMID- 16623658
TI  - Clinical and imaging metrics for monitoring disease progression in patients with
      multiple sclerosis.
AB  - Multiple sclerosis (MS) is an autoimmune disease of the CNS leading to clinical
      disability in 250,000-350,000 young adults in the USA and Europe. The disease
      affects both white matter (WM) and gray matter (GM) tissues of the brain and
      spinal cord. While WM disease is easily quantified using currently available
      magnetic resonance imaging (MRI) techniques, identification and quantification of
      GM disease present a daily challenge. Nonconventional brain and spinal cord MRI
      techniques, including magnetization transfer, MRI spectroscopy and diffusion
      tensor imaging, have improved our understanding of MS pathology in the deep GM.
      The sensitivity of high-resolution MRI obtained at a high magnetic field will
      improve the detection of spinal cord and brain cortical GM disease. The
      appropriate use of the above-mentioned techniques has the potential to more
      accurately explain the level of disability in MS patients.

PMID- 16623659
TI  - Highlights in opioid agonists and antagonists.
AB  - This review highlights new insights in to opioid agonists and antagonists,
      focusing on their mechanism of action with spinal and systemic administration,
      chronic use and main adverse effects. Short-cuts on some opioid agonists and
      antagonists of clinical interest are also presented, revealing potential clinical
      implications and future clinical directions as part of multimodal analgesia.

PMID- 16623660
TI  - Kinetic Th1/Th2 responses of transgenic mice with bacterial meningitis induced by
      Haemophilus influenzae.
AB  - To investigate the kinetic Th1/Th2 immunopathogenic mechanisms of Haemophilus
      influenzae meningitis, we established a murine experimental model of meningitis
      and elucidated the Th1/Th2 immune responses in T1/T2 doubly transgenic mice based
      on a BALB/c background under the control of the IFN-gamma (interferon-gamma)/IL-4
      (interleukin-4) promoters respectively. NTHi (non-typeable Haemophilus
      influenzae) meningitis was induced in these mice by inoculation with either a
      colonized (CNTHi) or invasive (INTHi) strain of NTHi. Mice inoculated with CNTHi
      displayed a less severe degree of disease in terms of clinical symptoms,
      mortality rate and brain histopathology. Conversely, INTHi-inoculated mice had
      more severe clinical symptoms. CNTHi-inoculated mice had a more significant Th1
      response in terms of a higher percentage and longer maintenance of Th1 cells, and
      more production of IFN-gamma from strain-specific antigen-stimulated splenocytes
      than INTHi-inoculated mice. In contrast, INTHi-inoculated mice had a more
      significant Th2 response. This was due to a significant increase in IL-4
      producing CD4(+) T-cells (Th2 cells) and more production of IL-4 from strain
      specific antigen-stimulated splenocytes accompanied by a rapid decline of Th1
      cells in INTHi-inoculated mice. In conclusion, the preferential Th1/Th2 trend in
      this murine model of NTHi meningitis is correlated with clinical severity as well
      as isolated characteristics of the pathogens themselves.

PMID- 16623662
TI  - Purification and characterization of a staphylokinase variant, K35R.
AB  - DGR [staphylokinase (Sak) variant K35R, in which lysine (K) at position 35 is
      replaced by arginine (R)], a recombinant mutant of the Staphylococcus aureus
      enzyme, is a promising drug for thrombotic disorders. In the present work, DGR
      was successfully overexpressed by the plasmid JF1125[pST-DGR] as a soluble
      cytoplasmic protein in a 30-litre fermentor that accounted for more than 50% of
      the total cellular protein. The expressed DGR was subsequently purified by using
      a simple three-step chromatographic purification process developed at a pilot
      scale. The clearance of host-cell-protein contaminants in the protein
      purification process was confirmed by SDS/PAGE and Western blotting, using rabbit
      antisera raised against Escherichia coli JF1125 cell proteins. SDS/PAGE,
      isoelectric focusing and HPLC-MS analysis indicated that the purified DGR is
      almost completely homogeneous. The purification process resulted in greater-than
      98% pure DGR and yielded up to 25.0 mg/g wet weight of cells. The effect of pH
      and temperature on the stability of DGR was investigated further. The results
      showed that DGR was highly stable at neutral pH and more stable than two other
      wild-type Saks, SakSTAR and Sak42D, when submitted to high temperatures.

PMID- 16623661
TI  - The structure of siglec-7 in complex with sialosides: leads for rational
      structure-based inhibitor design.
AB  - Siglecs (sialic acid binding Ig-like lectins) are transmembrane receptors for
      sialylated glycoconjugates that modulate cellular interactions and signalling
      events in the haematopoietic, immune and nervous systems. Siglec-7 is a
      structural prototype for the recently described family of immune inhibitory CD33
      related siglecs and is predominantly expressed on natural killer cells and
      monocytes, as well as subsets of CD8 T-cells. Siglec-specific inhibitors are
      desired for the detection of masked and unmasked forms of siglecs, to aid in
      dissection of signalling pathways and as tools to investigate siglecs as
      potential therapeutic targets. As a first step towards this end, we present the
      crystal structure of siglec-7 in complex with a sialylated ligand, the
      ganglioside analogue DSLc4 [alpha(2,3)/alpha(2,6) disialyl lactotetraosyl 2
      (trimethylsilyl)ethyl], which allows for a detailed description of the binding
      site, required for structure-guided inhibitor design. Mutagenesis and binding
      assays were used to demonstrate a key structural role for Lys131, a residue that
      changes conformation upon sialic acid binding. Differences between the binding
      sites of siglec family members were then exploited using alpha-methyl Neu5Ac (N
      acetylneuraminic acid) as a basic scaffold. A co-crystal of siglec-7 in complex
      with the sialoside inhibitor, oxamido-Neu5Ac [methyl alpha-9-(amino-oxalyl-amino)
      9-deoxy-Neu5Ac] and inhibition data for the sialosides gives clear leads for
      future inhibitor design.

PMID- 16623663
TI  - In-frame deletion in the EGF receptor alters kinase inhibition by gefitinib.
AB  - The existence of an in-frame deletion mutant correlates with the sensitivity of
      lung cancers to EGFR (epidermal growth factor receptor)-targeted tyrosine kinase
      inhibitors. We reported previously that the in-frame 15-bp deletional mutation
      (delE746-A750 type deletion) was constitutively active in cells. Kinetic
      parameters are important for characterizing an enzyme; however, it remains
      unclear whether the kinetic parameters of deletion mutant EGFR are similar to
      those of wild-type EGFR. We analysed autophosphorylation in response to ATP and
      inhibition of gefitinib for deletion mutant EGFR and wild-type EGFR. Kinetic
      studies, examining autophosphorylation, were carried out using EGFR fractions
      extracted from 293-pDelta15 and 293-pEGFR cells transfected with deletion mutant
      EGFR and wild-type EGFR respectively. We demonstrated the difference in
      activities between unstimulated wild-type (K(m) for ATP=4.0+/-0.3 microM) and
      mutant EGFR (K(m) for ATP=2.5+/-0.2 microM). There was no difference in K(m)
      values between EGF-stimulated wild-type EGFR (K(m) for ATP=1.9+/-0.1 microM) and
      deletion mutant EGFR (K(m) for ATP=2.2+/-0.2 microM). These results suggest that
      mutant EGFR is active without ligand stimulation. The K(i) value for gefitinib of
      the deletion mutant EGFR was much lower than that of wild-type EGFR. These
      results suggest that the deletion mutant EGFR has a higher affinity for gefitinib
      than wild-type EGFR.

PMID- 16623664
TI  - Cohesin protein SMC1 represses the nuclear receptor CAR-mediated synergistic
      activation of a human P450 gene by xenobiotics.
AB  - CAR (constitutive active/androstane receptor) regulates both the distal enhancer
      PBREM (phenobarbital-responsive enhancer module) and the proximal element OARE
      [OA (okadaic acid) response element] to synergistically up-regulate the
      endogenous CYP2B6 (where CYP is cytochrome P450) gene in HepG2 cells. In this up
      regulation, CAR acts as both a transcription factor and a co-regulator, directly
      binding to and enhancing PBREM upon activation by xenobiotics such as TCPOBOP
      {1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene} and indirectly associating with the
      OARE in response to OA [Swales, Kakizaki, Yamamoto, Inoue, Kobayashi and Negishi
      (2005) J. Biol. Chem. 280, 3458-3466]. We have now identified the cohesin protein
      SMC1 (structural maintenance of chromosomes 1) as a CAR-binding protein and
      characterized it as a negative regulator of OARE activity, thus repressing
      synergy. Treatment with SMC1 small interfering RNA augmented the synergistic up
      regulation of CYP2B6 expression 20-fold in HepG2 cells, while transient co
      expression of spliced form of SMC1 abrogated the synergistic activation of a 1.8
      kb CYP2B6 promoter. SMC1 indirectly binds to a 19 bp sequence (-236/-217)
      immediately downstream from the OARE in the CYP2B6 promoter. Both DNA affinity
      and chromatin immunoprecipitation assays showed that OA treatment dissociates
      SMC1 from the CYP2B6 promoter, reciprocating the indirect binding of CAR to OARE.
      These results are consistent with the conclusion that SMC1 binding represses OARE
      activity and its dissociation allows the recruitment of CAR to the OARE,
      synergizing PBREM activity and the expression of the CYP2B6 gene.

PMID- 16623666
TI  - Modality options for renal replacement therapy: the integrated care concept
      revisited.
AB  - As the End-stage renal disease population continues to grow, innovative
      strategies that optimize patient outcomes while capitalizing on the relative
      strengths of the existing modalities must be sought. Renal transplantation
      remains the preferred form of renal replacement therapy, but given the limited
      supply of donor organs, dialytic therapies will continue to constitute a large
      part of the modality mix. Matching patients to the most suitable modalities
      requires that a number of factors be considered. These include the patient's
      autonomy, medical and social factors, system-related issues, patient outcomes,
      and finances. While peritoneal dialysis and hemodialysis (HD) have traditionally
      been viewed as competing modalities, we propose that they, along with home and
      frequent HD regimens, may be used in a complementary manner, which is based on
      current evidence, and may provide optimal outcomes while containing treatment
      costs. In this review, we attempt to synthesize the current literature describing
      the various issues that affect modality selection, and offer an approach to
      achieving a balance between these many competing factors.

PMID- 16623665
TI  - Extracellular export of sphingosine kinase-1a contributes to the vascular S1P
      gradient.
AB  - Sphingosine 1-phosphate (S1P), produced by Sphks (sphingosine kinases), is a
      multifunctional lipid mediator that regulates immune cell trafficking and
      vascular development. Mammals maintain a large concentration gradient of S1P
      between vascular and extravascular compartments. Mechanisms by which S1P is
      released from cells and concentrated in the plasma are poorly understood. We
      recently demonstrated [Ancellin, Colmont, Su, Li, Mittereder, Chae, Stefansson,
      Liau and Hla (2002) J. Biol. Chem. 277, 6667-6675] that Sphk1 activity is
      constitutively secreted by vascular endothelial cells. In the present study, we
      show that among the five Sphk isoforms expressed in endothelial cells, the Sphk
      1a isoform is selectively secreted in HEK-293 cells (human embryonic kidney
      cells) and human umbilical-vein endothelial cells. In sharp contrast, Sphk2 is
      not secreted. The exported Sphk-1a isoform is enzymatically active and produced
      sufficient S1P to induce S1P receptor internalization. Wild-type mouse plasma
      contains significant Sphk activity (179 pmol x min(-1) x g(-1)). In contrast,
      Sphk1-/- mouse plasma has undetectable Sphk activity and approx. 65% reduction in
      S1P levels. Moreover, human plasma contains enzymatically active Sphk1 (46 pmol x
      min(-1) x g(-1)). These results suggest that export of Sphk-1a occurs under
      physiological conditions and may contribute to the establishment of the vascular
      S1P gradient.

PMID- 16623667
TI  - Stenosis in hemodialysis arteriovenous fistula: evaluation and treatment.
AB  - Vascular access complications are one of the main causes associated with an
      increase in morbidity and mortality in stage 5 chronic kidney disease patients.
      The arteriovenous fistula is regarded as the vascular access of choice for
      hemodialysis (HD) because of its superior patency and lower complication rates.
      Stenosis is considered the major cause of dysfunction of arteriovenous fistula.
      Despite the relatively low thrombosis rates of arteriovenous fistula,
      surveillance programs are necessary for detection of stenosis. We report a case
      of a HD patient who had never achieved an adequate Kt/V since the start of
      maintenance HD. During the investigation, abnormal findings were found on
      physical examination of the fistula, in addition to an alteration in intra-access
      pressure (IAP) measurements. A venous stenosis was diagnosed by Doppler
      ultrasound and then promptly treated with percutaneous transluminal angioplasty.
      The purpose of the discussion is to highlight the peculiarities of arteriovenous
      fistulae, methods of surveillance, including physical examination, IAP,
      recirculation, and measurements of blood flow, and the importance of the
      correction procedures for the stenosis.

PMID- 16623668
TI  - Intradialytic complications during hemodialysis.
AB  - With the advent of developments and advances in hemodialysis machine technology,
      dialysate water purification, and dialyzers, the clinical spectrum of
      intradialytic complications has changed over the decades. In the pioneering days
      of hemodialysis, patients could develop allergic reactions to dialyzer membranes,
      sterilizing and reprocessing agents, coupled with machines that could not
      accurately control ultrafiltration rates, and chemically and bacterially
      contaminated dialysate. Whereas today, although cardiovascular problems remain
      the most common intradialytic complication, these are mainly due to the time
      restraints of trying to cope with excessive dialytic weight gains and achieve
      target dry weight on a thrice weekly schedule, coupled with an aging elderly
      dialysis population with increasing co-morbidity.

PMID- 16623669
TI  - Gabapentin-induced coma in a patient with renal failure.
AB  - We describe a 60-year-old woman who became comatose after a single dose of
      gabapentin for right-sided sciatalgia. The patient was improved by hemodialysis.
      Gabapentin toxicity should be considered when mental status changes develop in
      patients with renal failure after even a single dose.

PMID- 16623670
TI  - Verapamil and mild hyperkalemia in hemodialysis patients: a potentially hazardous
      association.
AB  - During the past 3 years, 3 patients undergoing intermittent hemodialysis (or
      about to do so) in our hospital developed a third-degree atrioventricular block
      while being treated with verapamil for blood pressure or supraventricular
      arrhythmia. In the 3 cases, mild hyperkalemia was concomitant. The medical
      history of these patients revealed no intrinsic cause of atrioventricular
      conduction disturbance. We report herein the 3 cases and draw attention to the
      risks of atrioventricular block in this particular context.

PMID- 16623671
TI  - Evaluation of primary failure in native AV-fistulae (early fistula failure).
AB  - The most preferable method of vascular access (VA) in maintenance hemodialysis is
      a native arteriovenous fistula (AVF). Advanced age as well as the rapid increase
      in underlying diseases such as diabetic nephropathy and nephrosclerosis in these
      patients also means that the veins and arteries used to establish the AVF have
      undergone vascular damage, making construction of an AVF more difficult compared
      with earlier construction. Although there are various conditions under which
      arterial superficialization or AV graft must be chosen, it remains the rule that
      the first choice for VA should be AVF whenever possible. To improve postoperative
      results, it is necessary to reduce malfunctions immediately following surgery. We
      conducted a survey of 23 dialysis facilities throughout Japan and analyzed data
      from the past 3 years regarding the functionality of the AVF at initial puncture
      following construction of 5007 examples of newly constructed AVFs. Upon initial
      puncture, primary failure (PF) is defined as those cases in which thrombosis or
      inadequate blood flow occur. Primary failure occurred in 7.6% of the cases in
      this series, but there was a wide distribution of PF, 0.8% to 23.6%, because of
      differences in quality among facilities. This difference in PF is probably
      affected by technical aspects, the main factor being the characteristics of the
      patient. Survey responses included: (1) vascular damage of the veins and arteries
      used in creating the AVF and (2) the suitability of the location chosen for
      construction. In the data collected, many methods were used to repair those
      primary AFVs in which PF occurred. The salvage rate was 70%. Currently, the most
      preferable form of VA is AVF adhering to the principle that the proper timing of
      the choice and construction of AVF should consider the maturation period. To
      accomplish this, it is vital that vascular mapping be performed preoperatively to
      construct the AVF. If PF does occur, the cause should be thoroughly investigated
      and repairs made effectively.

PMID- 16623672
TI  - Large variations in prescriptions of gastrointestinal medications in hemodialysis
      patients on three continents: the Dialysis Outcomes and Practice Patterns Study
      (DOPPS).
AB  - Little is known about proton pump inhibitor (PPI) or H(2) receptor antagonist
      (HA) prescription patterns or regarding use of predictors in hemodialysis
      patients. Proton pump inhibitor and HA prescribing patterns were investigated in
      8628 hemodialysis patients from seven countries enrolled in the prospective,
      observational Dialysis Outcomes and Practice Patterns Study. Logistic regression
      examined predictors associated with PPI and HA use, adjusting for age, sex,
      country, time with end-stage renal disease, medications, 14 comorbid conditions,
      and the association between the number of comorbid conditions and the
      prescription of gastrointestinal (GI) medications. In a cross-section from
      February 1, 2000, 3.4% to 36.9% of patients received an HA and 0.8% to 26.9% took
      a PPI, depending upon the country. From 1996 to 2001, the prescription of HAs
      declined while PPI use increased. Facility use of HAs and PPIs ranged from 0% to
      94% of patients. H2 receptor antagonist or PPI use was significantly and
      independently associated with age, narcotic use, corticosteroids, acetaminophen,
      nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, selective
      serotonin reuptake inhibitors, coronary artery disease history, cardiovascular
      diseases other than hypertension or congestive heart failure, peripheral vascular
      disease, pulmonary disease, and GI bleed. Proton pump inhibitors or HAs were more
      likely to be prescribed in Italy, Spain, and the United Kingdom than in the
      United States. The odds of PPI prescription increased if serum phosphorus <5.5
      mEq/L or serum albumin <3.5 g/dL. Prescription of GI medications was associated
      with many comorbidities and use of several medications. Extreme variability of
      prescription patterns suggests that there is no standard approach in treatment
      practices.

PMID- 16623673
TI  - Cromolyn sodium: a potential therapy for uremic pruritus?
AB  - Uremic pruritus occurs in up to 50% of patients undergoing chronic hemodialysis.
      The pathogenesis of this disabling condition is unknown but likely involves
      multiple pathways involving the peripheral and central nervous system as well as
      local chemical and inflammatory mediators. Therapy has involved modification of
      the dialysis procedure, topical medications such as emollients, physical
      treatments such as ultraviolet light, and several oral medications such as
      antihistamines, activated charcoal, and gabapentin. Unfortunately, most of these
      therapies have not been subjected to rigorous clinical trials and clinical
      success has been variable. Two patients with disabling uremic pruritus refractory
      to multiple interventions are reported, who showed significant improvement in
      pruritus severity as assessed by a visual analog scale when they were treated
      with the mast cell stabilizer cromolyn sodium. Cessation of cromolyn resulted in
      return of pruritus, which improved with rechallenge with the medication. Cromolyn
      sodium may offer an alternative therapy for patients with refractory uremic
      pruritus, and should be subjected to a randomized placebo-controlled trial.

PMID- 16623674
TI  - The salvage of aneurysmal fistulae utilizing a modified buttonhole cannulation
      technique and multiple cannulators.
AB  - We describe the St Michael's Hospital (SMH) modified buttonhole (BH) cannulation
      technique as a method that offers a solution for fistulae with aneurysmal
      dilatation due to repetitive cannulation in a restricted area. This is a
      prospective cohort study of 14 chronic hemodialysis (HD) patients with
      problematic fistulae (marked aneurysmal formation and thinning of the overlying
      skin, bleeding during treatment, and prolonged hemostasis post-HD) because of
      repetitive, localized cannulation. Each patient was followed for 12 months. The
      protocol was as follows: creation of tunnel tracks by 1 to 3 experienced
      cannulators per patient, using sharp needles. After the tunnel tracks were
      established and cannulation was easily achieved with dull needles, additional
      cannulators were incorporated with the guidance of a mentor. Bleeding from
      cannulation sites during dialysis ceased within 2 weeks and skin damage resolved
      within 6 months in all patients. Hemostasis time postdialysis decreased from 24
      to 15 min. Cannulation pain scores decreased significantly. Access flows and
      dynamic venous pressure measurements remained unchanged. No interventions were
      required to maintain access patency. In 2 cases, the aneurysms became much less
      evident. Complications included one episode of septic arthritis and one contact
      dermatitis. A third patient developed acute bacterial endocarditis 9 months
      following completion of her follow-up. The SMH modified BH cannulation technique
      can salvage problematic fistulae, prevent further damage, and induce healing of
      the skin in the areas of repetitive cannulation. This technique can be
      successfully achieved by multiple cannulators in a busy full-care HD unit.

PMID- 16623675
TI  - Does an alteration of dialyzer design and geometry affect biocompatibility
      parameters?
AB  - The aim of the study was to assess the biocompatibility profile of a newly
      developed high-flux polysulfone dialyzer type (FX-class dialyzer). The new class
      of dialyzers incorporates a number of novel design features (including a new
      membrane) that have been developed specifically in order to enhance the removal
      of small- and middle-size molecules. The new FX dialyzer series was compared with
      the classical routinely used high-flux polysulfone F series of dialyzers. In an
      open prospective, randomized, crossover clinical study, concentrations of the C5a
      complement component, and leukocyte count in blood and various thrombogenicity
      parameters were evaluated before, and at 15 and 60 min of hemodialysis at both
      dialyzer inlet and outlet in 9 long-term hemodialysis patients using the FX60S
      dialyzers and, after crossover, the classical F60S, while in another 9 patients,
      the evaluation was made with the dialyzers used in reverse order. The comparison
      of dialyzers based on evaluation of the group including all procedures with the
      FX60S and the group including procedures with the F60S did not reveal significant
      differences in platelet count, activated partial thromboplastin times, plasma
      heparin levels, platelet factor-4, D-dimer, C5a, and leukocyte count at any point
      of the collecting period. Both dialyzer types showed a significant increase in
      the plasma levels of the thrombin-antithrombin III complexes; however, the
      measured levels were only slightly elevated compared with the upper end of the
      normal range. Biocompatibility parameters reflecting the behavior of platelets,
      fibrinolysis, complement activation, and leukopenia do not differ during dialysis
      with either the FX60S or the F60S despite their large differences in design and
      geometry features. Although coagulation activation, as evaluated by one of the
      parameters used, was slightly higher with the FX60S, it was still within the
      range seen with other highly biocompatible dialyzers and therefore is not
      indicative of any appreciable activation of the coagulation system. Thus, the
      incorporation of various performance-enhancing design features into the new FX
      class of dialyzers does not result in a deterioration of their biocompatibility
      profile, which is comparable to that of the classical F series of dialyzers.

PMID- 16623676
TI  - Determinants of metabolic acidosis among hemodialysis patients.
AB  - Metabolic acidosis is frequently present, poorly controlled, and associated with
      adverse effects among hemodialysis patients. Potential determinants of metabolic
      acidosis include endogenous acid production, administration of alkali,
      neutralization of acid by buffers, dilution of serum bicarbonate by interdialytic
      fluid gain, and loss of bicarbonate in stool. Understanding the relative
      importance of these determinants may help guide efforts to manage metabolic
      acidosis. We used chart abstraction, patient interviews, and laboratory testing
      to assess variables related to acid production (protein breakdown), alkali
      administration (dialysis dose, missed treatments, dialysate bicarbonate
      concentration, oral bicarbonate supplements), acid buffering (phosphorus
      binders), dilution of bicarbonate (interdialytic weight gain), and loss of
      bicarbonate in stool (diarrhea) for 190 randomly selected patients from 44
      hemodialysis facilities. We used multivariate analyses to determine which
      potential determinants were independently associated with predialysis serum
      bicarbonate levels. Of all patients, 30% had metabolic acidosis (serum
      bicarbonate level <22 mEq/L). On multivariate analysis, metabolic acidosis was
      more likely with increased protein nitrogen appearance (odds ratio [OR] 1.60 per
      0.2 g/kg/day, p=0.001) and less likely with increased Kt/V (OR 0.61 per 0.20
      increase in Kt/V, p<0.001) and with increased calcium carbonate use (OR 0.38 per
      2 g/day, p=0.003). Key determinants of metabolic acidosis among hemodialysis
      patients are protein breakdown, dialysis dose, and specific phosphorus binders.
      Further work is needed to develop interventions to address these determinants.

PMID- 16623678
TI  - Comment on middle molecule removal in low-flux polysulfone dialyzers: impact of
      flows and surface area on whole-body and dialyzer clearances.

PMID- 16623680
TI  - Subitizing in tactile perception.

PMID- 16623681
TI  - Don't talk about pink elephants! Speaker's control over leaking private
      information during language production.
AB  - Speakers' descriptions sometimes inappropriately refer to information known only
      to them, thereby "leaking" knowledge of that private information. We evaluated
      whether speakers can explicitly control such leakage in light of its
      communicative consequences. Speakers described mutually known objects (e.g., a
      triangle) that had size-contrasting matches that were privileged to the speakers
      (e.g., a larger triangle visible to the speakers only), so that use of a
      contrasting adjective (e.g., small) involved referring to the privileged
      information. Half the time, speakers were instructed to conceal the identity of
      the privileged object. If speakers can control their leaked references to
      privileged information, this conceal instruction should make such references less
      likely. Surprisingly, the conceal instruction caused speakers to refer to
      privileged objects more than they did in the baseline condition. Thus, not only
      do speakers have difficulty not leaking privileged information, but attempts to
      avoid such leakage only make it more likely.

PMID- 16623682
TI  - Spatial distance and mental construal of social events.
AB  - Construal-level theory proposes that increasing the reported spatial distance of
      events leads individuals to represent the events by their central, abstract,
      global features (high-level construal) rather than by their peripheral, concrete,
      local features (low-level construal). Results of two experiments indicated that
      participants preferred to identify actions as ends rather than as means to a
      greater extent when these actions occurred at a spatially distant, as opposed to
      near, location (Study 1), and that they used more abstract language to recall
      spatially distant events, compared with near events (Study 2). These findings
      suggest that spatially distant events are associated with high-level construals,
      and that spatial distance can be conceptualized as a dimension of psychological
      distance.

PMID- 16623683
TI  - Social discounting.
AB  - The amount of money a person was willing to forgo in order to give 75 dollars to
      another person decreased as a hyperbolic function of the perceived social
      distance between them. Similar hyperbolic functions have previously been shown to
      describe both time and probability discounting.

PMID- 16623684
TI  - The impact of emotion on perception: bias or enhanced processing?
AB  - Recent studies have shown that emotionally significant stimuli are often better
      identified than neutral stimuli. It is not clear, however, whether these results
      are due to enhanced perceptual processing or to a bias favoring the
      identification of emotionally significant stimuli over neutral stimuli. The
      present study used a two-alternative forced-choice perceptual identification task
      to disentangle the effects of bias and enhanced processing. We found that
      emotionally significant targets were better identified than neutral targets. In
      contrast, the emotional significance of the foil alternative had no effect on
      performance. The present results support the hypothesis that perceptual encoding
      of emotionally significant stimuli is enhanced.

PMID- 16623686
TI  - Domain specificity in experimental measures and participant recruitment: an
      application to risk-taking behavior.
AB  - We challenge the prevailing notion that risk taking is a stable trait, such that
      individuals show consistent risk-taking/aversive behavior across domains. We
      subscribe to an alternative approach that appreciates the domain-specific nature
      of risk taking. More important, we recognize heterogeneity of risk profiles among
      experimental samples and introduce a new methodology that takes this
      heterogeneity into account. Rather than using a convenient subject pool (i.e.,
      university students), as is typically done, we specifically targeted relevant
      subsamples to provide further validation of the domain-specific nature of risk
      taking. Our research shows that individuals who exhibit high levels of risk
      taking behavior in one content area (e.g., bungee jumpers taking recreational
      risks) can exhibit moderate levels in other risky domains (e.g., financial).
      Furthermore, our results indicate that risk taking among targeted subsamples can
      be explained within a cost-benefit framework and is largely mediated by the
      perceived benefit of the activity, and to a lesser extent by the perceived risk.

PMID- 16623685
TI  - Emotion facilitates perception and potentiates the perceptual benefits of
      attention.
AB  - Does emotion affect how people see? We investigated the effects of emotion and
      attention, as well as their conjoint effect, on contrast sensitivity, a dimension
      of early vision. We manipulated the emotional valence and the attentional
      distribution of cues preceding a target stimulus and asked observers to judge the
      orientation of the target as contrast varied. This study provides the first
      behavioral evidence that (a) emotion enhances contrast sensitivity irrespective
      of attention and (b) emotion potentiates the effect of attention on contrast
      sensitivity.

PMID- 16623687
TI  - The propensity effect: when foresight trumps hindsight.
AB  - The hindsight bias is an inability to disregard known outcome information when
      estimating earlier likelihoods of that outcome. The propensity effect, a reversal
      of this hindsight bias, is apparently unique to judgments involving momentum and
      trajectory (in which there is a strongly implied propensity toward a specific
      outcome). In the present study, the propensity effect occurred only in judgments
      involving dynamic stimuli (computer animations of traffic accidents vs. text
      descriptions), and only when foresight judgments were temporally near to (vs. far
      from) a focal outcome. This research was motivated by the applied question of
      whether the courtroom use of computer animation increases the hindsight bias in
      jurors' decision making; findings revealed that the hindsight bias was more than
      doubled when computer animations, rather than text-plus-diagram descriptions,
      were used. Therefore, in addition to providing theoretical insights of relevance
      to cognitive, perceptual, and social psychologists, these results have important
      legal implications.

PMID- 16623688
TI  - The anchoring-and-adjustment heuristic: why the adjustments are insufficient.
AB  - One way to make judgments under uncertainty is to anchor on information that
      comes to mind and adjust until a plausible estimate is reached. This anchoring
      and-adjustment heuristic is assumed to underlie many intuitive judgments, and
      insufficient adjustment is commonly invoked to explain judgmental biases.
      However, despite extensive research on anchoring effects, evidence for adjustment
      based anchoring biases has only recently been provided, and the causes of
      insufficient adjustment remain unclear. This research was designed to identify
      the origins of insufficient adjustment. The results of two sets of experiments
      indicate that adjustments from self-generated anchor values tend to be
      insufficient because they terminate once a plausible value is reached (Studies 1a
      and 1b) unless one is able and willing to search for a more accurate estimate
      (Studies 2a-2c).

PMID- 16623689
TI  - Gratitude and prosocial behavior: helping when it costs you.
AB  - The ability of the emotion gratitude to shape costly prosocial behavior was
      examined in three studies employing interpersonal emotion inductions and requests
      for assistance. Study 1 demonstrated that gratitude increases efforts to assist a
      benefactor even when such efforts are costly (i.e., hedonically negative), and
      that this increase differs from the effects of a general positive affective
      state. Additionally, mediational analyses revealed that gratitude, as opposed to
      simple awareness of reciprocity norms, drove helping behavior. Furthering the
      theory that gratitude mediates prosocial behavior, Study 2 replicated the
      findings of Study 1 and demonstrated gratitude's ability to function as an
      incidental emotion by showing it can increase assistance provided to strangers.
      Study 3 revealed that this incidental effect dissipates if one is made aware of
      the true cause of the emotional state. Implications of these findings for the
      role of gratitude in building relationships are discussed.

PMID- 16623690
TI  - I thought we could be friends, but ...: systematic miscommunication and defensive
      distancing as obstacles to cross-group friendship formation.
AB  - This study examined the precursors and consequences of systematic
      miscommunications regarding relationship interest during intergroup interaction.
      Pairs of previously unacquainted same-sex students (White-White, White-Chinese,
      or Chinese-Chinese) engaged in a relatively intimate controlled interaction.
      White participants who had had little prior contact with Chinese persons were
      more apt to exhibit a signal-amplification bias (i.e., to perceive that their
      overtures had conveyed more interest than was actually the case) in intergroup as
      compared with intragroup exchanges. In contrast, White participants with high
      levels of prior contact with Chinese persons and Chinese participants did not
      show enhanced signal amplification in intergroup relative to intragroup
      exchanges. These results support our hypothesis that lack of intergroup contact
      experience sets the stage for miscommunications regarding friendship interest.
      White participants' tendency to feel that they had initially communicated more
      interest in being friends than their Chinese partner mediated a downward shift in
      their actual friendship interest over time, suggesting that signal amplification
      triggers defensive distancing and ultimately lowers the likelihood of cross-group
      friendship formation.

PMID- 16623691
TI  - Prejudice expectations moderate preconscious attention to cues that are
      threatening to social identity.
AB  - Two studies examined whether chronic and situational expectations about being
      stigmatized predict attention toward cues that are threatening to social
      identity. In Study 1, women's chronic expectations about experiencing sexism were
      positively associated with their attention toward subliminal cues threatening to
      their social identity. In Study 2, women were vigilant toward subliminal cues
      threatening to their social identity when the experimental situation conveyed
      that their gender was devalued, but not when the experimental situation promoted
      value and respect for their gender. Women were vigilant toward consciously
      presented cues threatening to their social identity regardless of the attitudes
      the experimental context conveyed toward their group. These studies have
      important theoretical and practical implications for understanding the
      psychological experience of possessing a devalued social identity.

PMID- 16623692
TI  - The learned interpretation of cognitive fluency.
AB  - The fluency of cognitive processes influences many judgments: Fluently processed
      statements are judged to be true, fluently processed instances are judged to be
      frequent, and fluently processed names are judged to be famous. According to a
      cue-learning approach, these effects of experienced fluency arise because the
      fluency cue is interpreted differentially in accordance with its learned
      validity. Two experiments tested this account by manipulating the fluency cue's
      validity. Fluency was manipulated by color contrast (Experiment 1) and by
      required mental rotation (Experiment 2). If low fluency was correlated with a
      required affirmative or "old" response (and high fluency with a negative or "new"
      response) in a training phase, participants showed a reversal of the classic
      pattern in the recognition phase: Low-fluency stimuli had a higher probability
      than high-fluency stimuli to be classified as old. Thus, the interpretation and
      therefore the impact of fluency depended on the cue's learned validity.

PMID- 16623693
TI  - Chunking in task sequences modulates task inhibition.
AB  - In a study of the formation of representations of task sequences and its
      influence on task inhibition, participants first performed tasks in a predictable
      sequence (e.g., ABACBC) and then performed the tasks in a random sequence. Half
      of the participants were explicitly instructed about the predictable sequence,
      whereas the other participants did not receive these instructions. Task-sequence
      learning was inferred from shorter reaction times (RTs) in predictable relative
      to random sequences. Persisting inhibition of competing tasks was indicated by
      increased RTs in n- 2 task repetitions (e.g., ABA) compared with n- 2
      nonrepetitions (e.g., CBA). The results show task-sequence learning for both
      groups. However, task inhibition was reduced in predictable relative to random
      sequences among instructed-learning participants who formed an explicit
      representation of the task sequence, whereas sequence learning and task
      inhibition were independent in the noninstructed group. We hypothesize that the
      explicit instructions led to chunking of the task sequence, and that n- 2
      repetitions served as chunk points (ABA-CBC), so that within-chunk facilitation
      modulated the inhibition effect.

PMID- 16623694
TI  - Cognitive control in children: stroop interference and suppression of word
      reading.
AB  - The development of cognitive control and its relation to overcoming Stroop
      interference was assessed in a sample (N= 65) of elementary-school children.
      Subjects alternately performed Stroop color-naming trials and word-reading
      trials. In separate blocks, the colored Stroop items were non-color words
      (incongruent condition) or rows of asterisks (neutral condition). Younger
      children showed both larger Stroop interference in error rates and a greater
      slowing of word reading in the incongruent condition compared with older
      children. We conducted analyses of response time distributions that assessed the
      degree of word-reading suppression applied by younger and older children.
      Surprisingly, these analyses indicated that younger children engaged in stronger
      suppression than older children. We propose that greater Stroop interference
      among younger children is not due to lack of ability to suppress word reading,
      but instead is the result of a failure to consistently maintain the task set of
      color naming.

PMID- 16623695
TI  - Temporally unfolding neural representation of pictorial occlusion.
AB  - The human visual system possesses a remarkable ability to reconstruct the shape
      of an object that is partly occluded by an interposed surface. Behavioral results
      suggest that, under some circumstances, this perceptual process (termed amodal
      completion) progresses from an initial representation of local image features to
      a completed representation of a shape that may include features that are not
      explicitly present in the retinal image. Recent functional magnetic resonance
      imaging (fMRI) studies have shown that the completed surface is represented in
      early visual cortical areas. We used fMRI adaptation, combined with brief, masked
      exposures, to track the amodal completion process as it unfolds in early visual
      cortical regions. We report evidence for an evolution of the neural
      representation from the image-based feature representation to the completed
      representation. Our method offers the possibility of measuring changes in
      cortical activity using fMRI over a time scale of a few hundred milliseconds.

PMID- 16623696
TI  - In need of repair. Preserving the genome.

PMID- 16623697
TI  - The protein shuffle. Sequential interactions among components of the human
      nucleotide excision repair pathway.
AB  - Xeroderma pigmentosum (XP) is an inherited disease in which cells from patients
      exhibit defects in nucleotide excision repair (NER). XP proteins A-G are crucial
      in the processes of DNA damage recognition and incision, and patients with XP can
      carry mutations in any of the genes that specify these proteins. In mammalian
      cells, NER is a dynamic process in which a variety of proteins interact with one
      another, via modular domains, to carry out their functions. XP proteins are key
      players in several steps of the NER process, including DNA strand discrimination
      (XPA, in complex with replication protein A), repair complex formation (XPC, in
      complex with hHR23B; XPF, in complex with ERCC1) and repair factor recruitment
      (transcription factor IIH, in complex with XPG). Through these protein-protein
      interactions, various types of bulky DNA adducts can be recognized and repaired.
      Communication between the NER system and other cellular pathways is also achieved
      by selected binding of the various structural domains. Here, we summarize recent
      studies on the domain structures of human NER components and the regulatory
      networks that utilize these proteins. Data provided by these studies have helped
      to illuminate the complex molecular interactions among NER factors in the context
      of DNA repair.

PMID- 16623698
TI  - DNA mismatch repair system. Classical and fresh roles.
AB  - The molecular mechanisms of the DNA mismatch repair (MMR) system have been
      uncovered over the last decade, especially in prokaryotes. The results obtained
      for prokaryotic MMR proteins have provided a framework for the study of the MMR
      system in eukaryotic organisms, such as yeast, mouse and human, because the
      functions of MMR proteins have been conserved during evolution from bacteria to
      humans. However, mutations in eukaryotic MMR genes result in pleiotropic
      phenotypes in addition to MMR defects, suggesting that eukaryotic MMR proteins
      have evolved to gain more diverse and specific roles in multicellular organisms.
      Here, we summarize recent advances in the understanding of both prokaryotic and
      eukaryotic MMR systems and describe various new functions of MMR proteins that
      have been intensively researched during the last few years, including DNA damage
      surveillance and diversification of antibodies.

PMID- 16623699
TI  - Roles of base excision repair subpathways in correcting oxidized abasic sites in
      DNA.
AB  - Base excision DNA repair (BER) is fundamentally important in handling diverse
      lesions produced as a result of the intrinsic instability of DNA or by various
      endogenous and exogenous reactive species. Defects in the BER process have been
      associated with cancer susceptibility and neurodegenerative disorders. BER
      funnels diverse base lesions into a common intermediate, apurinic/apyrimidinic
      (AP) sites. The repair of AP sites is initiated by the major human AP
      endonuclease, Ape1, or by AP lyase activities associated with some DNA
      glycosylases. Subsequent steps follow either of two distinct BER subpathways
      distinguished by repair DNA synthesis of either a single nucleotide (short-patch
      BER) or multiple nucleotides (long-patch BER). As the major repair mode for
      regular AP sites, the short-patch BER pathway removes the incised AP lesion, a 5'
      deoxyribose-5-phosphate moiety, and replaces a single nucleotide using DNA
      polymerase (Polbeta). However, short-patch BER may have difficulty handling some
      types of lesions, as shown for the C1'-oxidized abasic residue, 2
      deoxyribonolactone (dL). Recent work indicates that dL is processed efficiently
      by Ape1, but that short-patch BER is derailed by the formation of stable covalent
      crosslinks between Ape1-incised dL and Polbeta. The long-patch BER subpathway
      effectively removes dL and thereby prevents the formation of DNA-protein
      crosslinks. In coping with dL, the cellular choice of BER subpathway may either
      completely repair the lesion, or complicate the repair process by forming a
      protein-DNA crosslink.

PMID- 16623700
TI  - Dual role of Nbs1 in the ataxia telangiectasia mutated-dependent DNA damage
      response.
AB  - The Nbs1 protein associates with Mre11 and Rad50 proteins to form the Mre11-Rad50
      Nbs1 complex, which plays an important role in the intracellular signaling
      pathway activated in response to DNA damage. Mutations in the genes for each of
      these three components of the Mre11-Rad50-Nbs1 complex result in human diseases
      characterized by genomic instability. Insight into the functions of Nbs1 in the
      DNA damage response mediated by the protein kinase, ataxia telangiectasia
      mutated, has been provided by recent studies. Nbs1 acts both as a downstream
      target of ataxia telangiectasia mutated in the S-phase checkpoint of the cell
      cycle as well as an upstream modulator or activator of ataxia telangiectasia
      mutated in the DNA damage response.

PMID- 16623701
TI  - Isochore structures in the chicken genome.
AB  - The availability of the complete chicken genome sequence provides an
      unprecedented opportunity to study the global genome organization at the sequence
      level. Delineating compositionally homogeneous G + C domains in DNA sequences can
      provide much insight into the understanding of the organization and biological
      functions of the chicken genome. A new segmentation algorithm, which is simple
      and fast, has been proposed to partition a given genome or DNA sequence into
      compositionally distinct domains. By applying the new segmentation algorithm to
      the draft chicken genome sequence, the mosaic organization of the chicken genome
      can be confirmed at the sequence level. It is shown herein that the chicken
      genome is also characterized by a mosaic structure of isochores, long DNA
      segments that are fairly homogeneous in the G + C content. Consequently, 25
      isochores longer than 2 Mb (megabases) have been identified in the chicken
      genome. These isochores have a fairly homogeneous G + C content and often
      correspond to meaningful biological units. With the aid of the technique of
      cumulative GC profile, we proposed an intuitive picture to display the
      distribution of segmentation points. The relationships between G + C content and
      the distributions of genes (CpG islands, and other genomic elements) were
      analyzed in a perceivable manner. The cumulative GC profile, equipped with the
      new segmentation algorithm, would be an appropriate starting point for analyzing
      the isochore structures of higher eukaryotic genomes.

PMID- 16623702
TI  - Recombinant purple acid phosphatase isoform 3 from sweet potato is an enzyme with
      a diiron metal center.
AB  - Purple acid phosphatases (PAPs) from sweet potato (sp) have been classified on
      the basis of their primary structure and the dinuclear metal center into isoforms
      spPAP1 [Fe(III)-Zn(II)] and spPAP2 [Fe(III)-Mn(II)]; for spPAP3 only the cDNA is
      known. With the aim of unraveling the character of the dinuclear metal center we
      report here the characterization of this isoform at the protein level. We cloned
      spPAP3 cDNA in a baculovirus and overexpressed this enzyme in Sf9 insect cells.
      Preparation of recombinant spPAP3 in two steps afforded pure enzyme with yields
      of 4.5 mg.L(-1) culture medium. This enzyme is a dimeric, disulfide-linked PAP of
      110 kDa, similar to known PAP isoforms from higher plants. Enzymatic studies and
      spectroscopic properties (max. absorption at 550-565 nm) indicated a diiron
      enzyme; quantitative and semiquantitative metal analysis using ICP-OES and TOF
      SIMS, respectively, revealed the presence of only iron in purified spPAP3. Metal
      replacement in the second metal-binding site upon preparation of the semiapo
      enzyme with Fe(II), Zn(II), or Mn(II) showed highest activities with Fe(II). The
      data show that recombinant spPAP3 has a diiron metal center. Site-directed
      mutagenesis was conducted to check catalytic efficiency at the atomic level.
      Tyr291 at the substrate-binding site in spPAP3 was mutated to His and Ala, the
      respective residues found in spPAP1 and spPAP2. Kinetic analysis showed that
      conversion of Tyr291 to His further optimized the performance of this protein as
      a diiron enzyme, whereas the Ala mutation weakened the catalytic efficiency
      regardless of the metal present in the second binding site.

PMID- 16623703
TI  - Interaction between catalytically inactive calpain and calpastatin. Evidence for
      its occurrence in stimulated cells.
AB  - Conformational changes in the calpain molecule following interaction with natural
      ligands can be monitored by the binding of a specific monoclonal antibody
      directed against the catalytic domain of the protease. None of these
      conformational states showed catalytic activity and probably represent
      intermediate forms preceding the active enzyme state. In its native inactive
      conformation, calpain shows very low affinity for this monoclonal antibody,
      whereas, on binding to the ligands Ca(2+), substrate or calpastatin, the affinity
      increases up to 10-fold, with calpastatin being the most effective. This
      methodology was also used to show that calpain undergoes similar conformational
      changes in intact cells exposed to stimuli that induce either a rise in
      intracellular [Ca(2+)] or extensive diffusion of calpastatin into the cytosol
      without affecting Ca(2+) homeostasis. The fact that the changes in the calpain
      state are also observed under the latter conditions indicates that calpastatin
      availability in the cytosol is the triggering event for calpain-calpastatin
      interaction, which is presumably involved in the control of the extent of calpain
      activation through translocation to specific sites of action.

PMID- 16623704
TI  - Identification of ERRalpha as a specific partner of PGC-1alpha for the activation
      of PDK4 gene expression in muscle.
AB  - Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulatory enzyme involved in
      switching the energy source from glucose to fatty acids in response to
      physiological conditions. Transcription of the PDK4 gene is activated by fasting
      or by the administration of a PPARalpha ligand in a tissue-specific manner. Here,
      we show that the two mechanisms are independent, and that ERRalpha is directly
      involved in PPARalpha-independent transcriptional activation of the PDK4 gene
      with PGC-1alpha as a specific partner. This conclusion is based on the following
      evidence. First, detailed mutation analyses of the cloned PDK4 gene promoter
      sequence identified a possible ERRalpha-binding motif as the PGC-1alpha
      responsive element. Second, overexpression of ERRalpha by cotransfection
      enhanced, and the knockout of it by shRNAs diminished, PGC-1alpha-dependent
      activation. Third, specific binding of ERRalpha to the identified PGC-1alpha
      responsive sequence was confirmed by the electrophoresis mobility shift assay.
      Finally, cell-type-specific responsiveness to PGC-1alpha was observed and this
      could be explained by differences in the expression levels of ERRalpha, however,
      ectopic expression of ERRalpha in poorly responsive cells did not restore PGC
      1alpha responsiveness, indicating that ERRalpha is necessary, but not sufficient
      for the response.

PMID- 16623705
TI  - Human cyclin B3. mRNA expression during the cell cycle and identification of
      three novel nonclassical nuclear localization signals.
AB  - Cyclins form complexes with cyclin-dependent kinases. By controlling activity of
      the enzymes, cyclins regulate progression through the cell cycle. A- and B-type
      cyclins were discovered due to their distinct appearance in S and G(2) phases and
      their rapid proteolytic destruction during mitosis. Transition from G(2) to
      mitosis is basically controlled by B-type cyclins. In mammals, two cyclin B
      proteins are well characterized, cyclin B1 and cyclin B2. Recently, a human
      cyclin B3 gene was described. In contrast to the expression pattern of other B
      type cyclins, we find cyclin B3 mRNA expressed not only in S and G(2)/M cells but
      also in G(0) and G(1). Human cyclin B3 is expressed in different variants. We
      show that one isoform remains in the cytoplasm, whereas the other variant is
      translocated to the nucleus. Transport to the nucleus is dependent on three
      autonomous nonclassical nuclear localization signals that where previously not
      implicated in nuclear translocation. It had been shown that cyclin B3
      coimmunoprecipitates with cdk2; but this complex does not exhibit any kinase
      activity. Furthermore, a degradation-resistant version of cyclin B3 can arrest
      cells in G(1) and G(2). Taken together with the finding that cyclin B3 mRNA is
      not only expressed in G(2)/M but is also detected in significant amounts in
      resting cells and in G(1) cells. This may suggest a dominant-negative function of
      human cyclin B3 in competition with activating cyclins in G(0) and the G(1) phase
      of the cell cycle.

PMID- 16623706
TI  - A potential mechanism of energy-metabolism oscillation in an aerobic chemostat
      culture of the yeast Saccharomyces cerevisiae.
AB  - The energy-metabolism oscillation in aerobic chemostat cultures of yeast is a
      periodic change of the respiro-fermentative and respiratory phase. In the respiro
      fermentative phase, the NADH level was kept high and respiration was suppressed,
      and glucose was anabolized into trehalose and glycogen at a rate comparable to
      that of catabolism. On the transition to the respiratory phase, cAMP levels
      increased triggering the breakdown of storage carbohydrates and the increased
      influx of glucose into the glycolytic pathway activated production of glycerol
      and ethanol consuming NADH. The resulting increase in the NAD(+)/NADH ratio
      stimulated respiration in combination with a decrease in the level of ATP, which
      was consumed mainly in the formation of biomass accompanying budding, and the
      accumulated ethanol and glycerol were gradually degraded by respiration via
      NAD(+)-dependent oxidation to acetate and the respiratory phase ceased after the
      recovery of NADH and ATP levels. However, the mRNA levels of both synthetic and
      degradative enzymes of storage carbohydrates were increased around the early
      respiro-fermentative phase, when storage carbohydrates are being synthesized,
      suggesting that the synthetic enzymes were expressed directly as active forms
      while the degradative enzymes were activated late by cAMP. In summary, the energy
      metabolism oscillation is basically regulated by a feedback loop of oxido
      reductive reactions of energy metabolism mediated by metabolites like NADH and
      ATP, and is modulated by metabolism of storage carbohydrates in combination of
      post-translational and transcriptional regulation of the related enzymes. A
      potential mechanism of energy-metabolism oscillation is proposed.

PMID- 16623707
TI  - Puroindoline-a and alpha1-purothionin form ion channels in giant liposomes but
      exert different toxic actions on murine cells.
AB  - Puroindoline-a (PIN-a) and alpha1-purothionin (alpha1-PTH), isolated from wheat
      endosperm of Triticum aestivum sp., have been suggested to play a role in plant
      defence mechanisms against phytopathogenic organisms. We investigated their
      ability to form pores when incorporated into giant liposomes using the patch
      clamp technique. PIN-a formed cationic channels (approximately 15 pS) with the
      following selectivity K(+) > Na(+) >> Cl(-). Also, alpha1-PTH formed channels of
      approximately 46 pS and 125 pS at +100 mV, the selectivity of which was Ca(2+) >
      Na(+) approximately K(+) >> Cl(-) and Cl(-) >> Na(+), respectively. In isolated
      mouse neuromuscular preparations, alpha1-PTH induced muscle membrane
      depolarization, leading to blockade of synaptic transmission and directly
      elicited muscle twitches. Also, alpha1-PTH caused swelling of differentiated
      neuroblastoma NG108-15 cells, membrane bleb formation, and disorganization of F
      actin. In contrast, similar concentrations of PIN-a had no detectable effects.
      The cytotoxic actions of alpha1-PTH on mammalian cells may be explained by its
      ability to induce cationic-selective channels.

PMID- 16623708
TI  - NANOGP8 is a retrogene expressed in cancers.
AB  - Nanog is a transcription factor that plays key roles in the self-renewal and
      maintenance of pluripotency in human embryonic stem (ES) cells. Among Nanog's 11
      pseudogenes, NANOGP8 theoretically could be a retrogene, but was considered
      unlikely as it has not been identified in any expressed sequence tags (ESTs). In
      this study, we found that NANOGP8 was expressed in several cancer cell lines and
      in all cancer tissues tested. The complete coding sequence was cloned and the
      sequence is highly homologous to that of Nanog. We were also able to detect its
      protein expression using anti-Nanog antibody in recombinant Escherichia coli and
      some cancer cell lines tested. In addition, expression of NANOGP8 in NIH3T3 cells
      can promote cell proliferation. The expression of NANOGP8 in cancer cell lines
      and cancer tissues suggests that NANOGP8 may play important roles in
      tumorigenesis. This work not only has potential significance in stem cell and
      cancer research, but it also raises the possibility that some of the human
      pseudogenes may have regulatory functions.

PMID- 16623709
TI  - Evolutionary origin and divergence of PQRFamide peptides and LPXRFamide peptides
      in the RFamide peptide family. Insights from novel lamprey RFamide peptides.
AB  - Among the RFamide peptide groups, PQRFamide peptides, such as neuropeptide FF
      (NPFF) and neuropeptide AF (NPAF), share a common C-terminal Pro-Gln-Arg-Phe
      NH(2) motif. LPXRFamide (X = L or Q) peptides, such as gonadotropin-inhibitory
      hormone (GnIH), frog growth hormone-releasing peptide (fGRP), goldfish LPXRFamide
      peptide and mammalian RFamide-related peptides (RFRPs), also share a C-terminal
      Leu-Pro-Leu/Gln-Arg-Phe-NH(2) motif. Such a similar C-terminal structure suggests
      that these two groups may have diverged from a common ancestral gene. In this
      study, we sought to clarify the evolutionary origin and divergence of these two
      groups, by identifying novel RFamide peptides from the brain of sea lamprey, one
      of only two extant groups of the oldest lineage of vertebrates, Agnatha. A novel
      lamprey RFamide peptide was identified by immunoaffinity purification using the
      antiserum against LPXRFamide peptide. The lamprey RFamide peptide did not contain
      a C-terminal LPXRFamide motif, but had the sequence SWGAPAEKFWMRAMPQRFamide
      (lamprey PQRFa). A cDNA of the precursor encoded one lamprey PQRFa and two
      related peptides. These related peptides, which also had the C-terminal PQRFamide
      motif, were further identified as mature endogenous ligands. Phylogenetic
      analysis revealed that lamprey PQRFamide peptide precursor belongs to the
      PQRFamide peptide group. In situ hybridization demonstrated that lamprey
      PQRFamide peptide mRNA is expressed in the regions predicted to be involved in
      neuroendocrine and behavioral functions. This is the first demonstration of the
      presence of RFamide peptides in the agnathan brain. Lamprey PQRFamide peptides
      are considered to have retained the most ancestral features of PQRFamide
      peptides.

PMID- 16623710
TI  - The antibody to GD3 ganglioside, R24, is rapidly endocytosed and recycled to the
      plasma membrane via the endocytic recycling compartment. Inhibitory effect of
      brefeldin A and monensin.
AB  - Gangliosides are sialic acid-containing glycosphingolipids present on mammalian
      plasma membranes, where they participate in cell-surface events such as
      modulation of growth factor receptors and cell-to-cell and cell-to-matrix
      interactions. Antibodies to gangliosides have been associated with a wide range
      of clinically identifiable acute and chronic neuropathy syndromes. In addition,
      antibodies to tumor-associated gangliosides are being used as therapeutic agents.
      Their binding to and release from cell membranes and intracellular destinations
      have not so far been extensively examined. In this study, we characterized in
      both GD3 ganglioside-expressing Chinese hamster ovary (CHO)-K1 and SK-Mel 28
      melanoma cells the intracellular trafficking and subcellular localization of the
      mouse monoclonal antibody to GD3, R24. By biochemical techniques and detailed
      confocal microscopic analysis, we demonstrate that the GD3-R24 antibody complex
      is rapidly and specifically internalized by a dynamin 2-independent pathway and
      then accumulates in the endocytic recycling compartment. In addition, we show
      that the R24 antibody exits the recycling compartment en route to the plasma
      membrane by a dynamin 2-dependent pathway sensitive to brefeldin A and monensin.
      Taken together, our results indicate that the GD3-R24 complex is endocytosed in
      GD3-expressing cells, accumulates in the recycling endosome, and is transported
      back to the plasma membrane via a route that involves clathrin-coated vesicles.

PMID- 16623711
TI  - Binding and activation of nitric oxide synthase isozymes by calmodulin EF hand
      pairs.
AB  - Calmodulin (CaM) is a cytosolic Ca(2+) signal-transducing protein that binds and
      activates many different cellular enzymes with physiological relevance, including
      the nitric oxide synthase (NOS) isozymes. CaM consists of two globular domains
      joined by a central linker; each domain contains an EF hand pair. Four different
      mutant CaM proteins were used to investigate the role of the two CaM EF hand
      pairs in the binding and activation of the mammalian inducible NOS (iNOS) and the
      constitutive NOS (cNOS) enzymes, endothelial NOS (eNOS) and neuronal NOS (nNOS).
      The role of the CaM EF hand pairs in different aspects of NOS enzymatic function
      was monitored using three assays that monitor electron transfer within a NOS
      homodimer. Gel filtration studies were used to determine the effect of Ca(2+) on
      the dimerization of iNOS when coexpressed with CaM and the mutant CaM proteins.
      Gel mobility shift assays were performed to determine binding stoichiometries of
      CaM proteins to synthetic NOS CaM-binding domain peptides. Our results show that
      the N-terminal EF hand pair of CaM contains important binding and activating
      elements for iNOS, whereas the N-terminal EF hand pair in conjunction with the
      central linker region is required for cNOS enzyme binding and activation. The
      iNOS enzyme must be coexpressed with wild-type CaM in vitro because of its
      propensity to aggregate when residues of the highly hydrophobic CaM-binding
      domain are exposed to an aqueous environment. A possible role for iNOS
      aggregation in vivo is also discussed.

PMID- 16623712
TI  - Combined use of selective inhibitors and fluorogenic substrates to study the
      specificity of somatic wild-type angiotensin-converting enzyme.
AB  - Somatic angiotensin-converting enzyme (ACE) contains two homologous domains, each
      bearing a functional active site. Studies on the selectivity of these ACE domains
      towards either substrates or inhibitors have mostly relied on the use of mutants
      or isolated domains of ACE. To determine directly the selectivity properties of
      each ACE domain, working with wild-type enzyme, we developed an approach based on
      the combined use of N-domain-selective and C-domain-selective ACE inhibitors and
      fluorogenic substrates. With this approach, marked differences in substrate
      selectivity were revealed between rat, mouse and human somatic ACE. In
      particular, the fluorogenic substrate Mca-Ala-Ser-Asp-Lys-DpaOH was shown to be a
      strict N-domain-selective substrate of mouse ACE, whereas with rat ACE it
      displayed marked C-domain selectivity. Similar differences in selectivity between
      these ACE species were also observed with a new fluorogenic substrate of ACE, Mca
      Arg-Pro-Pro-Gly-Phe-Ser-Pro-DpaOH. In support of these results, changes in amino
      acid composition in the binding site of these three ACE species were pinpointed.
      Together these data demonstrate that the substrate selectivity of the N-domain
      and C-domain depends on the ACE species. These results raise concerns about the
      interpretation of functional studies performed in animals using N-domain and C
      domain substrate selectivity data derived only from human ACE.

PMID- 16623713
TI  - Sulfatide with short fatty acid dominates in astrocytes and neurons.
AB  - Glycosphingolipids are located in cell membranes and the brain is especially
      enriched. We speculated that the subcellular location of glycosphingolipids
      depends on their fatty acid chain length because their sugar residues are
      constant, whereas fatty acid chain length can vary within the same molecule. To
      test this hypothesis we analysed the glycosphingolipid sulfatide, which is highly
      abundant in myelin and has mostly long fatty acids. We used a negative ion
      electrospray tandem mass spectrometry precursor ion scan to analyse the molecular
      species of sulfatide in cultured astrocytes and a mouse model of the human
      disease metachromatic leukodystrophy. In these arylsulfatase A (ASA)-deficient
      mice sulfatide accumulates intracellularly in neurons and astrocytes.
      Immunocytochemistry was also performed on cultured astrocytes and analysed using
      confocal laser scanning microscopy. Analyses of the molecular species showed that
      cultured astrocytes contained sulfatide with a predominance of stearic acid
      (C18), which was located in large intracellular vesicles throughout the cell body
      and along the processes. The same was seen in ASA-deficient mice, which
      accumulated a higher proportion (15 mol% compared with 8 mol% in control mice) of
      sulfatide with stearic acid. We conclude that the major fatty acid composition of
      sulfatide differs between white and grey matter, with neurons and astrocytes
      containing mostly short-chain fatty acids with an emphasis on stearic acid. Based
      on our results, we speculate that the fatty acid chain length of sulfatide might
      determine its intracellular (short chain) or extracellular (long chain) location
      and thereby its functions.

PMID- 16623714
TI  - A potential role for the Src-like adapter protein SLAP-2 in signaling by the
      colony stimulating factor-1 receptor.
AB  - The development of macrophages from myeloid progenitor cells is primarily
      controlled by the growth factor colony stimulating factor-1 (CSF-1) and its
      cognate receptor, a transmembrane tyrosine kinase encoded by the c-Fms proto
      oncogene. The CSF-1 receptor exerts its biological effects on cells via a range
      of signaling proteins including Erk1/2 and Akt. Here we have investigated the
      potential involvement of the Src-like adapter protein (SLAP-2) in signaling by
      the CSF-1 receptor in mouse bone marrow-derived macrophages. RT-PCR analysis
      revealed constitutive expression of the SLAP-2 gene in bone marrow macrophages.
      Surprisingly, co-immunoprecipitation and GST binding experiments demonstrated
      that the CSF-1 receptor could bind to SLAP-2 in a ligand-independent manner.
      Furthermore, the binding of SLAP-2 to the CSF-1 receptor involved multiple
      domains of SLAP-2. SLAP-2 also bound c-Cbl, with the interaction being mediated,
      at least in part, by the unique C-terminal domain of SLAP-2. Overexpression of
      SLAP-2 in bone marrow macrophages partially suppressed the CSF-1-induced tyrosine
      phosphorylation and/or expression level of a approximately 80 kDa protein without
      affecting CSF-1-induced global tyrosine phosphorylation, or activation of Akt or
      Erk1/2. Significantly, CSF-1 stimulation induced serine phosphorylation of SLAP
      2. Pharmacologic inhibition of specific protein kinases revealed that CSF-1
      induced phosphorylation of SLAP-2 was dependent on JNK activity. Taken together,
      our results suggest that SLAP-2 could potentially be involved in signaling by the
      CSF-1 receptor.

PMID- 16623715
TI  - SOX10, in combination with Sp1, regulates the endothelin receptor type B gene in
      human melanocyte lineage cells.
AB  - Waardenburg syndrome (WS) is an auditory-pigmentary disorder that exhibits
      varying combinations of sensorineural hearing loss and abnormal pigmentation of
      the hair and skin. WS type 4 (WS4), a subtype of WS, is characterized by the
      presence of the aganglionic megacolon and is associated with mutations in the
      gene encoding either endothelin 3, endothelin receptor type B (EDNRB), or Sry-box
      10 (SOX10). Here, we provide evidence that SOX10 regulates the expression of
      EDNRB gene in human melanocyte-lineage cells, as judged by RNA interference and
      chromatin immunoprecipitation analyses. Human melanocytes preferentially express
      the EDNRB transcripts derived from the conventional EDNRB promoter. SOX10
      transactivates the EDNRB promoter through the cis-acting elements, the two CA
      rich sequences and the GC box. Moreover, a transcription factor Sp1 enhances the
      degree of the SOX10-mediated transactivation of the EDNRB promoter through these
      cis-acting elements. Furthermore, we have shown that the EDNRB promoter is
      heavily methylated in HeLa human cervical cancer cells, lacking EDNRB expression,
      but not in melanocytes and HMV-II melanoma cells. The expression of EDNRB became
      detectable in HeLa cells after treatment with a demethylating reagent, 5'-aza-2'
      deoxycytidine, which was further enhanced in the transformed cells over
      expressing SOX10. We therefore suggest that SOX10, alone or in combination with
      Sp1, regulates transcription of the EDNRB gene, thereby ensuring appropriate
      expression level of EDNRB in human melanocytes.

PMID- 16623716
TI  - Role of gangliosides in the association of ErbB2 with lipid rafts in mammary
      epithelial HC11 cells.
AB  - We analyzed the role of gangliosides in the association of the ErbB2 receptor
      tyrosine-kinase (RTK) with lipid rafts in mammary epithelial HC11 cells. Scanning
      confocal microscopy experiments revealed a strict ErbB2-GM3 colocalization in
      wild-type cells. In addition, analysis of membrane fractions obtained using a
      linear sucrose gradient showed that ErbB2, epidermal growth factor receptor
      (EGFR) and Shc-p66 (proteins correlated with the ErbB2 signal transduction
      pathway) were preferentially enriched in lipid rafts together with gangliosides.
      Blocking of endogenous ganglioside synthesis by (+/-)-threo-1-phenyl-2
      decanoylamino-3-morpholino-1-propanol hydrochloride ([D]-PDMP) induced a drastic
      cell-surface redistribution of ErbB2, EGFR and Shc-p66, within the Triton-soluble
      fractions, as revealed by linear sucrose-gradient analysis. This redistribution
      was partially reverted when exogenous GM3 was added to ganglioside-depleted HC11
      cells. The results point out the key role of ganglioside GM3 in retaining ErbB2
      and signal-transduction-correlated proteins in lipid rafts.

PMID- 16623717
TI  - Local binding with globally distributed changes in a small protease inhibitor
      upon enzyme binding.
AB  - Complexation of the small serine protease inhibitor Schistocerca gregaria
      chymotrypsin inhibitor (SGCI), a member of the pacifastin inhibitor family, with
      bovine chymotrypsin was followed by NMR spectroscopy. (1)H-(15)N correlation
      (HSQC) spectra of the inhibitor with increasing amounts of the enzyme reveal
      tight and specific binding in agreement with biochemical data. Unexpectedly, and
      unparalleled among canonical serine protease inhibitors, not only residues in the
      protease-binding loop of the inhibitor, but also some segments of it located
      spatially far from the substrate-binding cleft of the enzyme were affected by
      complexation. However, besides changes, some of the dynamical features of the
      free inhibitor are retained in the complex. Comparison of the free and complexed
      inhibitor structures revealed that most, but not all, of the observed chemical
      shift changes can be attributed to minor structural transitions. We suggest that
      the classical 'scaffold + binding loop' model of canonical inhibitors might not
      be fully valid for the inhibitor family studied. In our view, this feature allows
      for the emergence of both taxon-specific and nontaxon-specific inhibitors in this
      group of small proteins.

PMID- 16623718
TI  - Atypical PKCzeta is involved in RhoA-dependent mitogenic signaling by the P2Y(12)
      receptor in C6 cells.
AB  - When nucleotide hydrolysis is prevented, agonists of the P2Y(12) receptor enhance
      the proliferation of C6 glioma cells by RhoA-dependent, protein kinase C (PKC)
      dependent activation of the extracellular signal-regulated kinase (ERK) pathway
      [Claes P, Grobben B, Van Kolen K, Roymans D & Slegers H (2001) Br J Pharmacol134,
      402-408; Grobben B, Claes P, Van Kolen K, Roymans D, Fransen P, Sys SU & Slegers
      H (2001) J Neurochem78, 1325-1338]. In this study, we show that ERK1/2
      phosphorylation was not affected by transfection of the cells with the Gbetagamma
      subunit-scavenging adrenergic receptor kinase peptide [betaARK1-(495-689)] or
      with Rap1GAPII, indicating that P2Y(12) receptor stimulation enhances ERK1/2
      phosphorylation by G(i)alpha subunit-mediated signaling independently of Rap1
      activation. Inhibition of the RhoA downstream effector Rho-associated coiled-coil
      containing kinase (ROCK) with Y-27632 did not affect the P2Y(12) receptor-induced
      increase in ERK1/2 phosphorylation but abrogated the mitogenic response.
      Involvement of growth factor receptor transactivation in the signaling towards
      ERK phosphorylation could be ruled out by the lack of an effect of PP2, AG1024,
      AG1296 or SU1498, inhibitors of Src, insulin-like growth factor receptor,
      platelet-derived growth factor receptor and vascular endothelial growth factor
      receptor kinase activity, respectively. Experiments with bisindolylmaleimide I
      and IX indicated the requirement of PKC activity. Classical and novel PKC
      isoforms could be excluded by treatment of the cells with Go6976 and calphostin
      C, whereas addition of a myristoylated PKCzeta pseudosubstrate inhibitor
      completely abolished P2Y(12) receptor-induced ERK1/2 activation. Moreover,
      coimmunoprecipitation experiments revealed PKCzeta/Raf1 and PKCzeta/ERK
      association, indicating the involvement of PKCzeta. From the data presented, we
      can conclude that the P2Y(12) receptor enhances cell proliferation by a G(i)alpha
      dependent, RhoA-dependent PKCzeta/Raf1/MEK/ERK pathway that requires activation
      of ROCK, which is not involved in ERK1/2 signaling.

PMID- 16623720
TI  - How many freshwater diatoms are pH specialists? A response to Pither & Aarssen
      (2005).
AB  - Pither & Aarssen (2005) propose a null model approach to assess the proportion of
      niche specialist taxa along ecological gradients. They apply this methodology to
      a large data set of lacustrine diatom assemblages and conclude that a majority of
      the taxa are generalists on a pH gradient. This conflicts with previous work,
      which shows that many diatom taxa have a statistically significant relationship
      with pH. We demonstrate the methods used by Pither & Aarssen (2005) have a high
      Type II error for rare taxa, and that this problem is compounded by the non
      uniform sampling of the pH gradient which effectively precludes acid-lake
      specialist diatoms from being recognized as such. We re-analyse the data used by
      Pither & Aarssen (2005) and show that most of the diatoms have a statistically
      significant relationship with pH, and we thus refute their conclusions that few
      diatom species are specialists.

PMID- 16623722
TI  - Minimum viable population sizes and global extinction risk are unrelated.
AB  - Theoretical and empirical work has shown that once reduced in size and
      geographical range, species face a considerably elevated risk of extinction. We
      predict minimum viable population sizes (MVP) for 1198 species based on long-term
      time-series data and model-averaged population dynamics simulations. The median
      MVP estimate was 1377 individuals (90% probability of persistence over 100 years)
      but the overall distribution was wide and strongly positively skewed. Factors
      commonly cited as correlating with extinction risk failed to predict MVP but were
      able to predict successfully the probability of World Conservation Union Listing.
      MVPs were most strongly related to local environmental variation rather than a
      species' intrinsic ecological and life history attributes. Further, the large
      variation in MVP across species is unrelated to (or at least dwarfed by) the
      anthropogenic threats that drive the global biodiversity crisis by causing once
      abundant species to decline.

PMID- 16623723
TI  - Predator disease out-break modulates top-down, bottom-up and climatic effects on
      herbivore population dynamics.
AB  - Human-introduced disease and climatic change are increasingly perturbing natural
      ecosystems worldwide, but scientists know very little about how they interact to
      affect ecological dynamics. An outbreak of canine parvovirus (CPV) in the wolf
      population on Isle Royale allowed us to test the transient effects of an
      introduced pathogen and global climatic variation on the dynamics of a three
      level food chain. Following the introduction of CPV, wolf numbers plummeted,
      precipitating a switch from top-down to bottom-up regulation of the moose
      population; consequently, the influence of climate on moose population growth
      rate doubled. This demonstrates that synergistic interactions between pathogens
      and climate can lead to shifts in trophic control, and suggests that predators in
      this system may play an important role in dampening the effects of climate change
      on the dynamics of their prey.

PMID- 16623724
TI  - Annual cycles of solar insolation predict spawning times of Caribbean corals.
AB  - Seasonal increases in sea surface temperature (SST) have long been considered the
      trigger for mass spawning events in reef corals. We critically examined the
      relationship between SST and the spawning activity of broadcasting corals in the
      tropical western Atlantic (Caribbean). This meta-analysis examined 12 species of
      broadcasting corals at 25 sites spanning 22 degrees of latitude (10 degrees-32
      degrees N) from Venezuela to Bermuda in the Atlantic Ocean from 1986 to 2004.
      Sigmoidal logit regression models were used to examine the relationship between
      the release of reef-coral gametes and the environmental variables SST and solar
      insolation defined as (1) the cumulative response 7-10 months prior to spawning
      (integral); (2) the rate of change at the time of spawning (derivative); and (3)
      the average for the month of spawning. The Quasi-Newton method was used to
      estimate the maximum likelihood of the response function. We demonstrate that the
      recent history and rate of change in temperature correlate poorly with the timing
      of spawning, while the average temperature during the month of spawning was
      significant (with all corals releasing gametes 28-30 degrees C, except
      Montastraea annularis, which released gametes at 27-30 degrees C). In contrast,
      the rate of change and the cumulative response of solar insolation cycles was a
      better predictor of gamete release, but solar insolation intensity at the time of
      spawning was not. These models have important implications for predicting coral
      reproductive cycles in all oceans, and for examining other marine phototrophic
      systems beyond corals.

PMID- 16623725
TI  - Reconciling niche and neutrality: the continuum hypothesis.
AB  - In this study, we ask if instead of being fundamentally opposed, niche and
      neutral theories could simply be located at the extremes of a continuum. First,
      we present a model of recruitment probabilities that combines both niche and
      neutral processes. From this model, we predict and test whether the relative
      importance of niche vs. neutral processes in controlling community dynamics will
      vary depending on community species richness, niche overlap and dispersal
      capabilities of species (both local and long distance). Results demonstrate that
      niche and neutrality form ends of a continuum from competitive to stochastic
      exclusion. In the absence of immigration, competitive exclusion tends to create a
      regular spacing of niches. However, immigration prevents the establishment of a
      limiting similarity. The equilibrium community consists of a set of complementary
      and redundant species, with their abundance determined, respectively, by the
      distribution of environmental conditions and the amount of immigration.

PMID- 16623726
TI  - Testing the role of parasites in driving the cyclic population dynamics of a
      gamebird.
AB  - The role of parasites in regulating populations has been the subject of debate.
      We tested whether parasites caused population cycles in red grouse by
      manipulating parasite intensities in four, paired 1 km(2) study areas during
      cyclic population declines over 4 years. Parasite reductions led to (1) larger
      grouse broods, (2) higher population densities in both autumn and spring, (3)
      reduced autumn population declines in one of two regions, and (4) reduced spring
      declines, but only in the first year. We infer that a single trophic interaction
      between a parasite and its host does not explain cyclic dynamics in spring
      breeding density in this species, although it contributed to the start of a
      cyclic decline. Another process was operating to drive the populations down.
      Together with our other results these findings emphasize that both trophic and
      intrinsic processes may act within populations to cause unstable dynamics.

PMID- 16623727
TI  - Ecosystem allometry: the scaling of nutrient stocks and primary productivity
      across plant communities.
AB  - A principal challenge in ecology is to integrate physiological function (e.g.
      photosynthesis) across a collection of individuals (e.g. plants of different
      species) to understand the functioning of the entire ensemble (e.g. primary
      productivity). The control that organism size exerts over physiological and
      ecological function suggests that allometry could be a powerful tool for scaling
      ecological processes across levels of organization. Here we use individual plant
      allometries to predict how nutrient content and productivity scale with total
      plant biomass (phytomass) in whole plant communities. As predicted by our model,
      net primary productivity as well as whole community nitrogen and phosphorus
      content all scale allometrically with phytomass across diverse plant communities,
      from tropical forest to arctic tundra. Importantly, productivity data deviate
      quantitatively from the theoretically derived prediction, and nutrient
      productivity (production per unit nutrient) of terrestrial plant communities
      decreases systematically with increasing total phytomass. These results are
      consistent with the existence of pronounced competitive size hierarchies. The
      previously undocumented generality of these 'ecosystem allometries' and their
      basis in the structure and function of individual plants will likely provide a
      useful quantitative framework for research linking plant traits to ecosystem
      processes.

PMID- 16623728
TI  - Parent birds assess nest predation risk and adjust their reproductive strategies.
AB  - Avian life history theory has long assumed that nest predation plays a minor role
      in shaping reproductive strategies. Yet, this assumption remains conspicuously
      untested by broad experiments that alter environmental risk of nest predation,
      despite the fact that nest predation is a major source of reproductive failure.
      Here, we examined whether parents can assess experimentally reduced nest
      predation risk and alter their reproductive strategies. We experimentally reduced
      nest predation risk and show that in safer environments parents increased
      investment in young through increased egg size, clutch mass, and the rate they
      fed nestlings. Parents also increased investment in female condition by
      increasing the rates that males fed incubating females at the nest, and
      decreasing the time that females spent incubating. These results demonstrate that
      birds can assess nest predation risk at large and that nest predation plays a key
      role in the expression of avian reproductive strategies.

PMID- 16623729
TI  - Early onset of secondary extinctions in ecological communities following the loss
      of top predators.
AB  - The large vulnerability of top predators to human-induced disturbances on
      ecosystems is a matter of growing concern. Because top predators often exert
      strong influence on their prey populations their extinction can have far-reaching
      consequences for the structure and functioning of ecosystems. It has, for
      example, been observed that the local loss of a predator can trigger a cascade of
      secondary extinctions. However, the time lags involved in such secondary
      extinctions remain unexplored. Here we show that the loss of a top predator leads
      to a significantly earlier onset of secondary extinctions in model communities
      than does the loss of a species from other trophic levels. Moreover, in most
      cases time to secondary extinction increases with increasing species richness. If
      local secondary extinctions occur early they are less likely to be balanced by
      immigration of species from local communities nearby. The implications of these
      results for community persistence and conservation priorities are discussed.

PMID- 16623730
TI  - Biological control agents elevate hantavirus by subsidizing deer mouse
      populations.
AB  - Biological control of exotic invasive plants using exotic insects is practiced
      under the assumption that biological control agents are safe if they do not
      directly attack non-target species. We tested this assumption by evaluating the
      potential for two host-specific biological control agents (Urophora spp.), widely
      established in North America for spotted knapweed (Centaurea maculosa) control,
      to indirectly elevate Sin Nombre hantavirus by providing food subsidies to
      populations of deer mice (Peromyscus maniculatus), the primary reservoir for the
      virus. We show that seropositive deer mice (mice testing positive for hantavirus)
      were over three times more abundant in the presence of the biocontrol food
      subsidy. Elevating densities of seropositive mice may increase risk of hantavirus
      infection in humans and significantly alter hantavirus ecology. Host specificity
      alone does not ensure safe biological control. To minimize indirect risks to non
      target species, biological control agents must suppress pest populations enough
      to reduce their own numbers.

PMID- 16623731
TI  - Patterns in potassium dynamics in forest ecosystems.
AB  - The biotic cycling of potassium (K) in forest systems has been relatively
      understudied in comparison with nitrogen (N) and phosphorus (P) despite its
      critical roles in maintaining the nutrition of primary production in forests. We
      investigated the ecological significance of K in forests from a literature review
      and data synthesis. We focused on (1) describing patterns of the effects of K
      availability on aboveground growth and change in foliar tissue of tree species
      from a variety of forests; and (2) documenting previously unreported
      relationships between hydrologic losses of K and N in forested watersheds from
      the Americas. In a review of studies examining tree growth under K
      manipulations/fertilizations, a high percentage (69% of studies) showed a
      positive response to increases in K availability in forest soils. In addition,
      76% of the tree studies reviewed showed a positive and significant increase in K
      concentrations in plant tissue after soil K manipulation/fertilization. A meta
      analysis on a subset of the reviewed studies was found to provide further
      evidence that potassium effects tree growth and increased tissue [K] with an
      effect size of 0.709 for growth and an overall effect size of 0.56. In our review
      of watershed studies, we observed that concentrations of K typically decreased
      during growing seasons in streams draining forested areas in the Temperate Zones
      and were responsive to vegetation disturbance in both temperate and tropical
      regions. We found a strong relationship (r2 = 0.42-0.99) between concentrations
      of K and N (another critical plant nutrient) in stream water, suggesting that
      similar mechanisms of biotic retention may control the flow of these nutrients.
      Furthermore, K dynamics appear to be unique among the base cations, e.g. calcium,
      magnesium, and sodium, because the others do not show similar seasonal patterns
      to K. We suggest that K may be important to the productivity and sustenance of
      many forests, and its dynamics and ecological significance warrant further study.
      We suggest that knowledge about the dynamics of this understudied element is
      imperative for our understanding patterns and processes in forest ecosystems.

PMID- 16623732
TI  - Seasonality and the dynamics of infectious diseases.
AB  - Seasonal variations in temperature, rainfall and resource availability are
      ubiquitous and can exert strong pressures on population dynamics. Infectious
      diseases provide some of the best-studied examples of the role of seasonality in
      shaping population fluctuations. In this paper, we review examples from human and
      wildlife disease systems to illustrate the challenges inherent in understanding
      the mechanisms and impacts of seasonal environmental drivers. Empirical evidence
      points to several biologically distinct mechanisms by which seasonality can
      impact host-pathogen interactions, including seasonal changes in host social
      behaviour and contact rates, variation in encounters with infective stages in the
      environment, annual pulses of host births and deaths and changes in host immune
      defences. Mathematical models and field observations show that the strength and
      mechanisms of seasonality can alter the spread and persistence of infectious
      diseases, and that population-level responses can range from simple annual cycles
      to more complex multiyear fluctuations. From an applied perspective,
      understanding the timing and causes of seasonality offers important insights into
      how parasite-host systems operate, how and when parasite control measures should
      be applied, and how disease risks will respond to anthropogenic climate change
      and altered patterns of seasonality. Finally, by focusing on well-studied
      examples of infectious diseases, we hope to highlight general insights that are
      relevant to other ecological interactions.

PMID- 16623733
TI  - Effects of species diversity on disease risk.
AB  - The transmission of infectious diseases is an inherently ecological process
      involving interactions among at least two, and often many, species. Not
      surprisingly, then, the species diversity of ecological communities can
      potentially affect the prevalence of infectious diseases. Although a number of
      studies have now identified effects of diversity on disease prevalence, the
      mechanisms underlying these effects remain unclear in many cases. Starting with
      simple epidemiological models, we describe a suite of mechanisms through which
      diversity could increase or decrease disease risk, and illustrate the potential
      applicability of these mechanisms for both vector-borne and non-vector-borne
      diseases, and for both specialist and generalist pathogens. We review examples of
      how these mechanisms may operate in specific disease systems. Because the effects
      of diversity on multi-host disease systems have been the subject of much recent
      research and controversy, we describe several recent efforts to delineate under
      what general conditions host diversity should increase or decrease disease
      prevalence, and illustrate these with examples. Both models and literature
      reviews suggest that high host diversity is more likely to decrease than increase
      disease risk. Reduced disease risk with increasing host diversity is especially
      likely when pathogen transmission is frequency-dependent, and when pathogen
      transmission is greater within species than between species, particularly when
      the most competent hosts are also relatively abundant and widespread. We conclude
      by identifying focal areas for future research, including (1) describing patterns
      of change in disease risk with changing diversity; (2) identifying the mechanisms
      responsible for observed changes in risk; (3) clarifying additional mechanisms in
      a wider range of epidemiological models; and (4) experimentally manipulating
      disease systems to assess the impact of proposed mechanisms.

PMID- 16623735
TI  - Molecular analysis of microbial communities identified in different developmental
      stages of Ixodes scapularis ticks from Westchester and Dutchess Counties, New
      York.
AB  - Ixodes scapularis ticks play an important role in the transmission of a wide
      variety of pathogens between various mammalian species, including humans.
      Pathogens transmitted by ticks include Borrelia, Anaplasma and Babesia. Although
      ticks may harbour both pathogenic and non-pathogenic microflora, little is known
      about how the diversity of the microflora within ticks may influence the
      transmission of pathogens. To begin addressing this question, we examined the
      composition of bacterial communities present in Ixodes scapularis collected from
      Westchester and Dutchess Counties, New York State, at different developmental and
      nutritional stages. Genetic fingerprints of bacterial populations were generated
      by temporal temperature gradient gel electrophoresis (TTGE) separation of
      individual polymerase chain reaction (PCR)-amplified 16S rRNA gene fragments,
      followed by DNA sequence analysis for bacterial identification. The fingerprints
      of the TTGE bands were grouped into five clusters. The most abundant DNA sequence
      found in all the samples was Rickettsia, followed by Pseudomonas and Borrelia.
      Ralstonia, Anaplasma, Enterobacterias, Moraxella, Rhodococcus and uncultured
      proteobacterium were present as well. We also determined the prevalence of
      Anaplasma phagocytophilum and Borrelia burgdorferi by PCR and DNA sequence
      analysis. Statistical analyses indicated significant variations in the bacterial
      communities depending on tick developmental stage and degree of engorgement. We
      suggest that these two elements affect microbial diversity within the tick and
      may in turn influence pathogen transmission to humans and animals after tick
      bite.

PMID- 16623736
TI  - Population dynamics of the ectomycorrhizal fungal species Tricholoma populinum
      and Tricholoma scalpturatum associated with black poplar under differing
      environmental conditions.
AB  - Fungi combine sexual reproduction and clonal propagation. The balance between
      these two reproductive modes affects establishment dynamics, and ultimately the
      evolutionary potential of populations. The pattern of colonization was studied in
      two species of ectomycorrhizal fungi: Tricholoma populinum and Tricholoma
      scalpturatum. The former is considered to be a host specialist whereas T.
      scalpturatum is a generalist taxon. Fruit bodies of both basidiomycete species
      were mapped and collected over several years from a black poplar (Populus nigra)
      stand, at two different sites. Multilocus genotypes (= genets) were identified
      based on the analysis of random amplified polymorphic DNA (RAPD) patterns, inter
      simple sequence repeat (ISSR) patterns and restriction fragment length
      polymorphisms (RFLPs) in the ribosomal DNA intergenic spacer (rDNA IGS). The
      genetic analyses revealed differences in local population dynamics between the
      two species. Tricholoma scalpturatum tended to capture new space through sexual
      spores whereas T. populinum did this by clonal growth, suggesting trade-offs in
      allocation of resources at the genet level. Genet numbers and sizes strongly
      differ between the two study sites, perhaps as a result of abiotic disturbance on
      mycelial establishment and genet behaviour.

PMID- 16623737
TI  - Characterization and quantification of ammonia-oxidizing bacteria in eutrophic
      coastal marine sediments using polyphasic molecular approaches and
      immunofluorescence staining.
AB  - Tokyo Bay, a eutrophic bay in Japan, receives nutrients from wastewater plants
      and other urban diffuse sources via river input. A transect was conducted along a
      line from the Arakawa River into Tokyo Bay to investigate the ecological
      relationship between the river outflow and the distribution, abundance and
      population structure of ammonia-oxidizing bacteria (AOB). Five surficial marine
      sediments were collected and analysed with polyphasic approaches. Heterogeneity
      and genetic diversity of beta-AOB populations were examined using restriction
      fragment length polymorphism (RFLP) analysis of 16S rRNA and amoA genes. A shift
      of the microbial community was detected in samples along the transect. Both 16S
      rRNA and amoA genes generated polymorphisms in the restriction profiles that were
      distinguishable at each sampling site. Two 16S rRNA gene libraries were
      constructed using the reverse transcription polymerase chain reaction (RT-PCR)
      method to determine the major ammonia oxidizers maintaining high cellular rRNA
      content. Two major groups were observed in the Nitrosomonas lineage; no
      Nitrosospira were detected. The effort to isolate novel AOB was successful; the
      isolate dominated in the gene libraries. For quantitative analysis, a real-time
      PCR assay targeting the 16S rRNA gene was developed. The population sizes of beta
      AOB ranged from 1.6 x 10(7) to 3.0 x 10(8) cells g(-1) in dry sediments, which
      corresponded to 0.1-1.1% of the total bacterial population. An immunofluorescence
      staining using anti-hydroxylamine oxidoreductase (HAO) antibody was also tested
      to obtain complementary data. The population sizes of ammonia oxidizers ranged
      between 2.4 x 10(8) and 1.2 x 10(9) cells g(-1) of dry sediments, which
      corresponded to 1.2-4.3% of the total bacterial fraction. Ammonia-oxidizing
      bacteria cell numbers deduced by the two methods were correlated (R = 0.79, P <
      0.01). In both methods, the number of AOB increased with the distance from the
      river mouth; ammonia-oxidizing bacteria were most numerous at B30, where the
      ammonium concentration in the porewater was markedly lower and the nitrite
      concentration was slightly higher than nearby sites. These results reveal spatial
      distribution and shifts in the population structure of AOB corresponding to
      nutrients and organic inputs from the river run-off and phytoplankton bloom.

PMID- 16623738
TI  - Evaluation of quantitative polymerase chain reaction-based approaches for
      determining gene copy and gene transcript numbers in environmental samples.
AB  - Quantitative polymerase chain reaction (Q-PCR) amplification is widely applied
      for determining gene and transcript numbers within environmental samples. This
      research evaluated Q-PCR reproducibility via TaqMan assays quantifying 16S rRNA
      gene and transcript numbers in sediments, within and between replicate Q-PCR
      assays. Intra-assay variation in 16S rRNA gene numbers in replicate DNA samples
      was low (coefficients of variation; CV from 3.2 to 5.2%). However, variability
      increased using replicated standard curves within separate Q-PCR assays (CV from
      11.2% to 26%), indicating absolute comparison of gene numbers between Q-PCR
      assays was less reliable. 16S rRNA transcript quantification was evaluated using
      standard curves of diluted RNA or cDNA (before, or following, reverse
      transcription). These standard curves were statistically different with cDNA
      derived curves giving higher r(2) values and Q-PCR efficiencies. Template
      concentrations used in Q-PCR also affected 16S rRNA gene and transcript numbers.
      For DNA, 10(-3) dilutions yielded higher gene numbers than 10(-1) and 10(-2)
      dilutions. Conversely, RNA template dilution reduced numbers of transcripts
      detected. Finally, different nucleic acid isolation methods also resulted in gene
      and transcript number variability. This research demonstrates Q-PCR determination
      of absolute numbers of genes and transcripts using environmental nucleic acids
      should be treated cautiously.

PMID- 16623739
TI  - Removal of selenate from sulfate-containing media by sulfate-reducing bacterial
      biofilms.
AB  - A biofilm-selected strain of a Desulfomicrobium sp. removed selenate from
      solution to sub-micromolar concentrations during growth on lactate (or hydrogen)
      and sulfate. Under sulfate-limited growth conditions, selenium was enzymatically
      reduced to selenide. Under excess sulfate conditions, selenate removal was
      primarily by enzymatic reduction to elemental selenium. Sequestration by biofilms
      was greater under the latter condition. Experiments with washed cell suspensions
      showed that high sulfate concentrations inhibited cell-specific selenate
      reduction, but when growing cells were exposed to selenate, the biomass increase
      achieved during incubations with abundant sulfate resulted in more rapid selenate
      removal. The addition of small amounts of sulfite, or thiosulfate, ameliorated
      this inhibition. Nitrate also inhibited selenate reduction in washed cell
      suspensions, apparently due to a general oxidizing effect. These results suggest
      that where biofilm-based sulfate-reducing bacteria (SRB) bioreactors are
      considered for the treatment of mixed metalliferous wastes that contain selenium
      oxyanions, adequate selenate removal should be achievable under a range of
      environmental conditions. The form and fate of the precipitated product will,
      however, be influenced by the dominant reduction pathway, which is controlled by
      environmental variables.

PMID- 16623740
TI  - Transcription of a 'photosynthetic' T4-type phage during infection of a marine
      cyanobacterium.
AB  - The transcription of S-PM2 phage following infection of Synechococcus sp. WH7803,
      a marine cyanobacterium, was analysed by quantitative real-time PCR. Unlike the
      distantly related coliphage T4, there were only two (early and late) instead of
      three (early, middle and late) classes of transcripts during the developmental
      cycle of the phage. This difference is consistent with the absence from the S-PM2
      genome of T4-like middle mode promoter sequences and the transcription factors
      associated with their recognition. Phage S-PM2 carries the 'photosynthetic' genes
      psbA and psbD that encode homologues of the host photosystem II proteins D1 and
      D2. Transcripts of the phage psbA gene appeared soon after infection and remained
      at high levels until lysis. Throughout the course of infection, the
      photosynthetic capacity of the cells remained constant. A considerable transient
      increase in the abundance of the host psbA transcripts occurred shortly after
      infection, suggesting that the host responds to the trauma of phage infection in
      a similar way as it does to a variety of other environmental stresses. The very
      substantial transcription of the phage psbA gene during the latter phase of phage
      infection suggests that S-PM2 has acquired this cellular gene to ensure that D1
      levels and thus photosynthesis are fully maintained until the infected cell
      finally lyses. Unexpectedly, transcripts of a phage-encoded S-layer protein gene
      were among the earliest and most abundant detected, suggesting that this partial
      homologue of a host protein plays an important role in the S-PM2 infection
      process.

PMID- 16623741
TI  - Distribution of the Mycobacterium community and polycyclic aromatic hydrocarbons
      (PAHs) among different size fractions of a long-term PAH-contaminated soil.
AB  - Summary Mycobacterium is often isolated from polycyclic aromatic hydrocarbon
      (PAH)-contaminated soil as degraders of PAHs. In model systems, Mycobacterium
      shows attachment to the PAH substrate source, which is considered to be a
      particular adaptation to low bioavailability as it results into increased
      substrate flux to the degraders. To examine whether PAH-degrading Mycobacterium
      in real PAH-contaminated soils, in analogy with model systems, are preferentially
      associated with PAH-enriched soil particles, the distribution of PAHs, of the PAH
      mineralizing capacity and of Mycobacterium over different fractions of a soil
      with an aged PAH contamination was investigated. The clay fraction contained the
      majority of the PAHs and showed immediate pyrene- and phenanthrene-mineralizing
      activity upon addition of (14)C-labelled pyrene or phenanthrene. In contrast, the
      sand and silt fractions showed a lag time of 15-26 h for phenanthrene and 3-6
      days for pyrene mineralization. The maximum pyrene and phenanthrene
      mineralization rates of the clay fraction expressed per gram fraction were three
      to six times higher than those of the sand and silt fractions. Most-probable
      number (MPN)-polymerase chain reaction demonstrated that Mycobacterium
      represented about 10% of the eubacteria in the clay fraction, while this was only
      about 0.1% in the sand and silt fractions, indicating accumulation of
      Mycobacterium in the PAH-enriched clay fraction. The Mycobacterium community
      composition in the clay fraction represented all dominant Mycobacterium
      populations of the bulk soil and included especially species related to
      Mycobacterium pyrenivorans, which was also recovered as one of the dominant
      species in the eubacterial communities of the bulk soil and the clay fraction.
      Moreover, Mycobacterium could be identified among the major culturable PAH
      degrading populations in both the bulk soil and the clay fraction. The results
      demonstrate that PAH-degrading mycobacteria are mainly associated with the PAH
      enriched clay fraction of the examined PAH-contaminated soil and hence, that also
      in the environmental setting of a PAH-contaminated soil, Mycobacterium might
      experience advantages connected to substrate source attachment.

PMID- 16623742
TI  - Rapid analysis of two food-borne microbial communities at the species level by
      Fourier-transform infrared microspectroscopy.
AB  - The species composition of microbial communities in natural habitats may be
      extremely complex and therefore a quantitative analysis of the fraction each
      species contributes to the consortium has proven to be difficult. During recent
      years, the identification of bacterial pure cultures based on their infrared
      spectra has been established. Fourier-transform infrared microspectroscopy now
      proceeds a step further and allows identification of microorganisms directly
      plated from community dilutions. Infrared spectra of microcolonies of 70-250
      microm in diameter can be recorded without producing a pure culture of the
      isolate. We have applied this novel technique for quantitative comparative
      analysis of two undefined, geographically separated food-borne smear cheese
      microbial consortia of limited complexity. Due to the high degree of automation,
      up to 200 microcolonies could be identified in 1 day and, in total, 3170 infrared
      spectra of microcolonies were recorded. The results obtained have been verified
      by Fourier-transform infrared macrospectroscopy and 16S rDNA sequencing.
      Interestingly, although the communities were unrelated, Staphylococcus equorum,
      Corynebacterium casei, Arthrobacter casei and Brevibacterium linens were found to
      be part of both consortia, however, with different incidence. In addition,
      Corynebacterium variabile, Microbacterium gubbeenense, Brachybacterium
      alimentarium, Enterococcus faecalis and an unknown species were detected in
      either one of the consortia.

PMID- 16623743
TI  - Photorhabdus luminescens toxin-induced permeability change in Manduca sexta and
      Tenebrio molitor midgut brush border membrane and in unilamellar phospholipid
      vesicle.
AB  - Photorhabdus luminescens, a Gram-negative bacterium, secretes a protein toxin (PL
      toxin) that is toxic to insects. In this study, the effects of the PL toxin on
      large receptor-free unilamellar phospholipid vesicles (LUVs) of Manduca sexta and
      on brush border membrane vesicles (BBMVs) of M. sexta and Tenebrio molitor were
      examined. Cry1Ac served as a positive control in our experiments due to its known
      channel-forming activity on M. sexta. Voltage clamping assays with dissected
      midguts of M. sexta and T. molitor clearly showed that both Cry1Ac and PL toxin
      caused channel formation in the midguts, although channel formation was not
      detected for T. molitor midguts under Cry1Ac and it was less sensitive to PL
      toxin than to Cry1Ac for M. sexta midguts. Calcein release experiments showed
      that both toxins made LUVs (unilamellar lipid vesicles) permeable, and at some
      concentrations of the toxins such permeabilizing effects were pH-dependent. The
      lowest concentrations of PL toxin were more than 600-fold and 24-fold lower to
      induce BBMV permeability of T. molitor and M. sexta than those to induce calcein
      release from LUVs of M. sexta. These further support that PL toxin is responsible
      for channel formation in the larvae midguts. The lower concentration to induce
      permeability in BBMV than in LUV is, probably, attributable to that BBMV has PL
      toxin receptors that facilitate the toxin to induce permeabilization.
      Furthermore, our results indicate that the effects of PL toxin on BBMV
      permeability of M. sexta were not significantly influenced by Gal Nac, but those
      of Cry1Ac were. This implies that PL toxin and Cry1Ac might use different
      molecular binding sites in BBMV to cause channel formation.

PMID- 16623744
TI  - Numbers and locations of native bacteria on field-grown wheat roots quantified by
      fluorescence in situ hybridization (FISH).
AB  - Native bacteria, Pseudomonas and filamentous bacteria were quantified and
      localized on wheat roots grown in the field using fluorescence in situ
      hybridization (FISH). Seminal roots were sampled through the season from
      unploughed soil in a conservation farming system. Such soils are spatially
      heterogeneous, and many roots grow slowly through hard soil with cracks and pores
      containing dead roots remnant from previous crops. Root and rhizosphere
      morphology, and contact with soil particles were preserved, and autofluorescence
      was avoided by observing sections in the far-red with Cy5 and Cy5.5
      fluorochromes. Spatial analyses showed that bacteria were embedded in a stable
      matrix (biofilm) within 11 microm of the root surface (range 2-30 microm) and
      were clustered on 40% of roots. Half the clusters co-located with axial grooves
      between epidermal cells, soil particles, cap cells or root hairs; the other half
      were not associated with visible features. Across all wheat roots, although
      variable, bacteria averaged 15.4 x 10(5) cells per mm(3) rhizosphere, and of
      these, Pseudomonas and filaments comprised 10% and 4%, respectively, with minor
      effects of sample time, and no effect of plant age. Root caps were most heavily
      colonized by bacteria along roots, and elongation zones least heavily colonized.
      Pseudomonas varied little with root development and were 17% of bacteria on the
      elongation zone. Filamentous bacteria were not found on the elongation zone. The
      most significant factor to rhizosphere populations along a wheat root, however,
      was contact with dead root remnants, where Pseudomonas were reduced but filaments
      increased to 57% of bacteria (P < 0.001). This corresponded with analyses of root
      remnants showing they were heavily colonized by bacteria, with 48% filaments (P <
      0.001) and 1.4%Pseudomonas (P = 0.014). Efforts to manage rhizosphere bacteria
      for sustainable agricultural systems should continue to focus on root cap and
      mucilage chemistry, and remnant roots as sources of beneficial bacteria.

PMID- 16623745
TI  - Changes in equine hindgut bacterial populations during oligofructose-induced
      laminitis.
AB  - In the horse, carbohydrate overload is thought to play an integral role in the
      onset of laminitis by drastically altering the profile of bacterial populations
      in the hindgut. The objectives of this study were to develop and validate
      microbial ecology methods to monitor changes in bacterial populations throughout
      the course of experimentally induced laminitis and to identify the predominant
      oligofructose-utilizing organisms. Laminitis was induced in five horses by
      administration of oligofructose. Faecal specimens were collected at 8 h intervals
      from 72 h before to 72 h after the administration of oligofructose. Hindgut
      microbiota able to utilize oligofructose were enumerated throughout the course of
      the experiment using habitat-simulating medium. Isolates were collected and
      representatives identified by 16S rRNA gene sequencing. The majority of these
      isolates collected belonged to the genus Streptococcus, 91% of which were
      identified as being most closely related to Streptococcus infantarius ssp. coli.
      Furthermore, S. infantarius ssp. coli was the predominant oligofructose-utilizing
      organism isolated before the onset of lameness. Fluorescence in situ
      hybridization probes developed to specifically target the isolated Streptococcus
      spp. demonstrated marked population increases between 8 and 16 h post
      oligofructose administration. This was followed by a rapid population decline
      which corresponded with a sharp decline in faecal pH and subsequently lameness at
      24-32 h post oligofructose administration. This research suggests that
      streptococci within the Streptococcus bovis/equinus complex may be involved in
      the series of events which precede the onset of laminitis in the horse.

PMID- 16623746
TI  - Anaerobic arsenite oxidation by novel denitrifying isolates.
AB  - Autotrophic microorganisms have been isolated that are able to derive energy from
      the oxidation of arsenite [As(III)] to arsenate [As(V)] under aerobic conditions.
      Based on chemical energetics, microbial oxidation of As(III) can occur in the
      absence of oxygen, and may be relevant in some environments. Enrichment cultures
      were established from an arsenic contaminated industrial soil amended with
      As(III) as the electron donor, inorganic C as the carbon source and nitrate as
      the electron acceptor. In the active enrichment cultures, oxidation of As(III)
      was stoichiometrically coupled to the reduction of NO(3) (-). Two autotrophic
      As(III)-oxidizing strains were isolated that completely oxidized 5 mM As(III)
      within 7 days under denitrifying conditions. Based on 16S rRNA gene sequencing
      results, strain DAO1 was 99% related to Azoarcus and strain DAO10 was most
      closely related to a Sinorhizobium. The nitrous oxide reductase (nosZ) and the
      RuBisCO Type II (cbbM) genes were successfully amplified from both isolates
      underscoring their ability to denitrify and fix CO(2) while coupled to As(III)
      oxidation. Although limited work has been done to examine the diversity of
      anaerobic autotrophic oxidizers of As(III), this process may be an important
      component in the biological cycling of arsenic within the environment.

PMID- 16623747
TI  - Bacterial and archaeal phylotypes associated with distinct mineralogical layers
      of a white smoker spire from a deep-sea hydrothermal vent site (9 degrees N, East
      Pacific Rise).
AB  - A diffusely venting chimney spire from the East Pacific Rise (9 degrees N) was
      analysed by petrographic thin sectioning and 16S rRNA gene cloning and sequencing
      in parallel, to correlate microbial community composition with mineralogy and
      inferred in situ conditions within the chimney mineral matrix. Both approaches
      indicated a zonation of the chimney spire into distinct microhabitats for
      different bacteria and archaea. The thermal gradient inferred from the mineral
      composition and porosity of the chimney was consistent with the distribution of
      bacterial and archaeal phylotypes in the chimney matrix. A novel phylogenetic
      lineage of euryarchaeota was found that co-occurred with clones related to
      cultured hyperthermophilic archaea. A few phylotypes related to mesophilic
      bacteria were found in the hot core of the chimney, indicating that seawater
      influx during retrieval and cooling of these highly porous structures can entrain
      microorganisms into chimney layers that are not their native habitat.

PMID- 16623748
TI  - Use of microcosms to determine the survival of the fish pathogen Tenacibaculum
      maritimum in seawater.
AB  - The survival of the fish pathogen Tenacibaculum maritimum in different seawater
      microcosms was investigated during 160 days. The persistence of culturable cells
      was greater in sterile than in natural seawater. Standard plate counts showed
      that T. maritimum survived in sterile seawater for more than 5 months at
      concentration around 10(3) cfu ml(-1). However, T. maritimum proved to be very
      labile in non-sterile seawater, rendering culturable cells no longer than 5 days.
      These results were confirmed when DNA-based methods were applied. Regardless of
      the microcosms used, epifluorescence microscopy counts remained at about 10(6)
      cells ml(-1) throughout the experiment, even though we can not distinguish T.
      maritimum in the case of non-sterile microcosms. Resuscitation assays with
      addition of fresh medium to non-sterile microcosms did not favour the recovery of
      T. maritimum on solid media. Although morphological changes from filamentous to
      spheres were observed after 3 days in the non-sterile microcosms, in the case of
      the sterile microcosms this change was observed at the sixth day. The
      biochemical, physiological, serological and genetic characteristics were
      unaffected in the sterile microcosms. The overall results contribute to a better
      understanding of the behaviour of T. maritimum in natural seawater and suggest
      that the aquatic bacterial population play an important role in the survival of
      this fish pathogen.

PMID- 16623749
TI  - Statistical methods for characterizing diversity of microbial communities by
      analysis of terminal restriction fragment length polymorphisms of 16S rRNA genes.
AB  - The analysis of terminal restriction fragment length polymorphisms (T-RFLP) of
      16S rRNA genes has proven to be a facile means to compare microbial communities
      and presumptively identify abundant members. The method provides data that can be
      used to compare different communities based on similarity or distance measures.
      Once communities have been clustered into groups, clone libraries can be prepared
      from sample(s) that are representative of each group in order to determine the
      phylogeny of the numerically abundant populations in a community. In this paper
      methods are introduced for the statistical analysis of T-RFLP data that include
      objective methods for (i) determining a baseline so that 'true' peaks in
      electropherograms can be identified; (ii) a means to compare electropherograms
      and bin fragments of similar size; (iii) clustering algorithms that can be used
      to identify communities that are similar to one another; and (iv) a means to
      select samples that are representative of a cluster that can be used to construct
      16S rRNA gene clone libraries. The methods for data analysis were tested using
      simulated data with assumptions and parameters that corresponded to actual data.
      The simulation results demonstrated the usefulness of these methods in their
      ability to recover the true microbial community structure generated under the
      assumptions made. Software for implementing these methods is available at
      http://www.ibest.uidaho.edu/tools/trflp_stats/index.php.

PMID- 16623750
TI  - Detection of phosphonoacetate degradation and phnA genes in soil bacteria from
      distinct geographical origins suggest its possible biogenic origin.
AB  - Phosphonoacetate is regarded as an antiviral xenobiotic whose mineralization can
      be catalysed by an enzyme, phosphonoacetate hydrolase, encoded by the phnA gene.
      To date the enzyme's activity has been detected in only a limited number of
      bacteria. Its expression has been shown to occur in a manner independent of the
      phosphate status of the cell, in direct contrast to the general rule of
      organophosphonate metabolism being under the control of the pho regulon. In this
      study the environmental occurrence of the phnA gene was evaluated by polymerase
      chain reaction amplification of DNA extracts obtained directly from various soil
      environments. Sensitivity of this method was improved such that a positive result
      was routinely obtained with soil spiked with as few as 6 colony-forming units
      (cfu) per gram of soil of Pseudomonas fluorescens 23F (phnA(+)). When total DNA
      from a variety of Northern Irish, Greek and Bolivian soils was tested, all were
      positive for phnA. Bacteria capable of utilizing phosphonoacetate as sole carbon,
      energy and phosphorus source, with the release of essentially equimolar
      concentrations of phosphate to the culture supernatant, were isolated from all
      soil samples tested. Analysis of three such isolates revealed all to be species
      of Pseudomonas sensu stricto, possessing phosphonoacetate hydrolase activity in
      cell-free extracts. Sequence determination of the phnA gene revealed a similarity
      of the putative protein sequences at levels of 98.3-99.3% between the Pseudomonas
      strains. This is the first study to use molecular methods to investigate the
      distribution of a gene encoding organophosphonate metabolism, and indicates that
      the phnA gene is ubiquitous within soils from geographically distinct regions.
      Such an observation supports the proposition that phosphonoacetate is a compound
      that may also have a biogenic origin.

PMID- 16623752
TI  - The role of melatonin in immuno-enhancement: potential application in cancer.
AB  - Melatonin, a neurohormone produced mainly by the pineal gland, is a modulator of
      haemopoiesis and of immune cell production and function, both in vivo and in
      vitro. Physiologically, melatonin is associated with T-helper 1 (Th1) cytokines,
      and its administration favours Th1 priming. In both normal and leukaemic mice,
      melatonin administration results in quantitative and functional enhancement of
      natural killer (NK) cells, whose role is to mediate defenses against virus
      infected and cancer cells. Melatonin appears to regulate cell dynamics, including
      the proliferative and maturational stages of virtually all haemopoietic and
      immune cells lineages involved in host defense - not only NK cells but also T and
      B lymphocytes, granulocytes and monocytes - in both bone marrow and tissues. In
      particular, melatonin is a powerful antiapoptotic signal promoting the survival
      of normal granulocytes and B lymphocytes. In mice bearing mid-stage leukaemia,
      daily administration of melatonin results in a survival index of 30-40% vs. 0% in
      untreated mice. Thus, melatonin seems to have a fundamental role as a system
      regulator in haemopoiesis and immuno-enhancement, appears to be closely involved
      in several fundamental aspects of host defense and has the potential to be useful
      as an adjuvant tumour immunotherapeutic agent.

PMID- 16623753
TI  - Accelerated growth of intestinal tumours after radiation exposure in Mlh1
      knockout mice: evaluation of the late effect of radiation on a mouse model of
      HNPCC.
AB  - Mlh1-knockout mice have been developed as a useful model of hereditary non
      polyposis colorectal cancer (HNPCC). In this study, we analyzed the pathology of
      gastrointestinal tumours (GIT) in these mice in detail and examined the possible
      effects of ionizing radiation on the induction of intestinal tumours to evaluate
      the late response to radiotherapy in HNPCC. Mlh1-/- mice spontaneously developed
      GIT and thymic lymphomas by 48 weeks. GIT included not only well differentiated
      adenocarcinomas but also poorly differentiated and mucinous adenocarcinomas,
      suggesting that this mouse is a good model for HNPCC. In contrast to colon
      cancers from HNPCC patients, however, carcinomas of Mlh1-/- mice expressed p53
      and showed a lack of transforming growth factor (TGF)-betaRII mutation, which
      resulted in the expression of TGF-betaRII protein. Irradiation of 10-week-old
      Mlh1-/- mice accelerated GIT development but had little effect at 2 weeks. Mlh1+/
      and Mlh1+/+ mice were not susceptible to spontaneous or radiation-induced thymic
      lymphomas and GIT until 72 weeks after birth. The development and pathology of
      GIT in Mlh1-/- mice suggest that this mouse is a good model for HNPCC, although
      tumour-related responsible genes might be different from HNPCC. As X-ray exposure
      promoted carcinogenesis of GIT in adult Mlh1-/- mice, an increased risk of
      secondary cancers after radiotherapy for HNPCC patients should be taken into
      consideration.

PMID- 16623754
TI  - Characterization of the myelotoxicity of chloramphenicol succinate in the B6C3F1
      mouse.
AB  - Chloramphenicol (CAP) is haemotoxic in man, inducing two types of toxicity.
      First, a dose-related, reversible anaemia with reticulocytopenia, sometimes seen
      in conjunction with leucopenia and thrombocytopenia; this form of toxicity
      develops during drug treatment. The second haemotoxicity is aplastic anaemia (AA)
      which is evident in the blood as severe pancytopenia. AA development is not dose
      related and occurs weeks or months after treatment. We wish, in the longer term,
      to investigate CAP-induced AA in the busulphan-pretreated mouse. However, as a
      prelude to that study, we wanted to characterize in detail the reversible
      haemotoxicity of CAP succinate (CAPS), administered at high dose levels in the
      mouse, and follow the recovery of the bone marrow in the post-dosing period.
      Female B6C3F1 mice were gavaged with CAPS at 0, 2500 and 3500 mg/kg, daily, for 5
      days and sampled (n = 5) at 1, 7, 14 and 21 days post-dosing. Blood, bone marrow
      and spleen samples were analysed and clonogenic assays carried out. At day 1 post
      dosing, at both CAPS dose levels, decreases were seen in erythrocytes and
      erythrocyte precursors; marrow erythroid cells were reduced. Reductions were also
      evident in splenic nucleated cell counts, blood high fluorescence ratio (HFR)
      reticulocyte counts and total reticulocyte counts; burst-forming units-erythroid
      and colony-forming units-erythroid showed decreases. At day 7 post-dosing (2500
      mg/kg CAPS), there was regeneration of erythrocyte production, with marked
      splenic erythropoietic activity, and raised blood HFR reticulocytes. At day 7, at
      3500 mg/kg CAPS, erythrocyte and reticulocyte parameters remained depressed. At
      14 days post-dosing (2500 mg/kg CAPS), many erythrocyte parameters had returned
      to normal; at 3500 mg/kg CAPS, there was erythroid regeneration. By 21 days post
      dosing, at both CAPS dose levels, most erythrocytic parameters were equivalent to
      control values. For leucocyte parameters, there was some depression at day 1 post
      dosing (at both CAPS dose levels) and signs of recovery at day 7. At days 14 and
      21 post-dosing, most leucocyte parameters were close to control values. Marrow
      smears at day 1 post-dosing (at both CAPS dose levels) showed vacuolation of
      early normoblasts, of myeloid and of monocytic precursors. We conclude that the
      administration of CAPS at 2500 and 3500 mg/kg for 5 days induced significant
      myelotoxicity in female B6C3F1 mice, with cessation of erythropoiesis at day 1
      post-dosing; recovery was seen over the following 7/14 days. The blood HFR
      reticulocyte count was a precise indicator of CAPS-induced depressive effects and
      subsequent recovery. It is concluded that the administration of five daily doses
      of CAPS at 2500 and 3500 mg/kg to the female B6C3F1 mouse induces an anaemia with
      reticulocytopenia, in conjunction with leucopenia, in the immediate post-dosing
      period; no evidence was seen at 21 days post-dosing of peripheral blood
      pancytopenia or a hypocellular/acellular bone marrow, which are both
      characteristic features of AA in man.

PMID- 16623755
TI  - Association of plasminogen activators and matrix metalloproteinase-9 proteolytic
      cascade with blood-CNS barrier damage of angiostrongyliasis.
AB  - Blood-central nervous system (blood-CNS) barrier breakdown, an important
      pathophysiological event in meningitis, results in extravasation of leucocytes
      into subarachnoid space. The blood-CNS barrier disruption is mediated by
      primarily two enzyme systems, the plasminogen activators (PAs) and matrix
      metalloproteinases (MMPs). The present study showed that the activities of tissue
      type PA (tPA), urokinase-type activator (uPA) and MMP-9 in cerebrospinal-like
      fluid (CSF-like fluid) were significantly increased in mice with eosinophilic
      meningitis compared with uninfected mice. Eosinophilia significantly correlated
      with tPA, uPA and MMP-9 activities, and albumin concentration. In addition, when
      GM6001, a specific matrix metalloproteinase blocker, was injected into infected
      mice, MMP-9 activity and total protein concentrations declined from their
      preinjection highs. These results suggest that the PAs and MMP-9 proteolytic
      cascade may be associated with blood-CNS barrier disruption in eosinophilic
      meningitis caused by Angiostrongylus cantonensis.

PMID- 16623756
TI  - Development of diabetes in non-obese diabetic mice promotes Chlamydia pneumoniae
      dissemination from lung to peripheral blood.
AB  - We examined a possible association between development of diabetes in non-obese
      diabetic (NOD) mice and dissemination of Chlamydia (Chlamydophila) pneumoniae
      from lung to peripheral blood. By real-time reverse transcription-polymerase
      chain reaction (RT-PCR) with primers for C. pneumoniae 16S rRNA, following
      multiple intranasal inoculations, we detected bacteria in lung in NOD mice with
      diabetes (38.5%) as well as Institute of Cancer Research, USA (ICR) mice (40%),
      but prevalence of bacteria in NOD mice without diabetes (pre-diabetic NOD mice
      and non-diabetic retired NOD mice) was very low (4.8%). The bacteria were only
      detected in peripheral blood mononuclear cells (PBMCs) cultured with
      hydrocortisone of the NOD mice with diabetes (53.8%). Results of immunostaining
      with fluorescein isothiocyanate-conjugated antichlamydia monoclonal antibody also
      showed the presence of bacterial antigens in the lungs and the PBMCs judged as
      positive by the RT-PCR. However, C. pneumoniae from cultured PBMCs of all NOD
      mice was undetected by cultivation method with inclusion-forming units assay. In
      addition, no influence of C. pneumoniae intranasal inoculation on development of
      diabetes in NOD mice was confirmed. Thus, the development of diabetes in NOD
      mouse appears to be one of critical factors for promoting the dissemination of C.
      pneumoniae from lung to peripheral blood.

PMID- 16623757
TI  - Histopathology in a murine model of anthrax.
AB  - Systemic anthrax infection is usually fatal even with optimal medical care.
      Further insights into anthrax pathogenesis are therefore urgently needed to
      develop more effective therapies. Animal models that reproduce human disease will
      facilitate this research. Here, we describe the detailed histopathology of
      systemic anthrax infection in A/J mice infected with Bacillus anthracis Sterne, a
      strain with reduced virulence for humans. Subcutaneous infection leads to
      systemic disease with multiple pathologies including oedema, haemorrhage,
      secondary pneumonia and lymphocytolysis. These pathologies bear marked similarity
      to primary pathologies observed during human disease. Therefore, this simple,
      small animal model will allow researchers to study the major pathologies observed
      in humans, while permitting experimentation in more widely available Biosafety
      Level 2 facilities.

PMID- 16623758
TI  - Intragranulomatous necrosis in pulmonary granulomas is not related to resistance
      against Mycobacterium tuberculosis infection in experimental murine models
      induced by aerosol.
AB  - Intragranulomatous necrosis is a primary feature in the natural history of human
      tuberculosis (TB). Unfortunately, this phenomenon is not usually seen in the
      experimental TB murine model. Artificial induction of this necrosis in pulmonary
      granulomas (INPG) may be achieved through aerosol inoculation of
      lipopolysaccharide (LPS) 3 weeks after Mycobacterium tuberculosis infection. At
      week 9 post-infection, the centre of primary granulomas became larger, showing
      eosinophilic necrosis. Interestingly, INPG induction was related to mice strains
      C57BL/6 and 129/Sv, but not to BALB/c and DBA/2. Furthermore, the same pattern
      was obtained with the induction of infection using a clinical M. tuberculosis
      strain (UTE 0335R) that naturally induces INPG. In all the mice strains tested,
      the study of pulmonary mRNA expression revealed a tendency to increase or to
      maintain the expression of RANTES, interferon-gamma, tumour necrosis factor and
      iNOS, in both LPS- and UTE 0335R-induced INPG, thus suggesting that this response
      must be necessary but not sufficient for inducing INPG. Our work supports that
      INPG induction is a local phenomenon unrelated to the resistant (C57BL/6 and
      BALB/c) or susceptible (129/Sv and DBA/2) background of mice strains against M.
      tuberculosis infection.

PMID- 16623759
TI  - Deletion mapping of chromosome 13q in head and neck squamous cell carcinoma in
      Indian patients: correlation with prognosis of the tumour.
AB  - Deletions in chromosome (chr.) 13q occur frequently in head and neck squamous
      cell carcinoma (HNSCC). Previous studies failed to identify common deleted
      regions in chr.13q, though several candidate tumour suppressor genes (TSGs) loci,
      e.g. BRCA2, RB1 and BRCAX have been localized in this chromosome, as well as no
      prognostic significance of the deletion has been reported. Thus, in the present
      study, deletion mapping of chr. 13q has been done in 55 primary HNSCC samples of
      Indian patients using 11 highly polymorphic microsatellite markers of which three
      were intragenic to BRCA2 gene, one intragenic to RB1 gene and another from BRCAX
      locus. The deletion in chr.13q was significantly associated with progression of
      HNSCC. High frequencies (27-39%) of loss of heterozygosity were found in 13q13.1
      (BRCA2), 13q14.2 (RB1), 13q21.2-22.1 (BRCAX) and 13q31.1 regions. Deletions in
      the BRCA2 and RB1 regions were significantly correlated. The four highly deleted
      regions were associated with clinical stage and histological grades of the tumour
      as well as poor patient outcome. Deletion in the 13q31.1 region was only found to
      be associated with HPV infection. High frequencies (11-23%) of microsatellite
      size alteration (MA) were seen to overlap with the highly deleted regions. Forty
      per cent of the samples showed rare biallelic alteration whereas loss of normal
      copy of chromosome 13q was seen in five tumours. Thus, it seems that the putative
      TSGs located in the BRCAX and 13q31.1 regions as well as the BRCA2 and RB1 genes
      may have some cumulative effect in progression and poor prognosis of HNSCC.
      Significant association between deletion in BRCA2 and RB1 gene loci may indicate
      functional relationship between the genes in this tumour progression.

PMID- 16623762
TI  - The use of genomewide ENU mutagenesis screens to unravel complex mammalian
      traits: identifying genes that regulate organ-specific and systemic autoimmunity.
AB  - T-cell development is perhaps one of the best understood processes of mammalian
      cell differentiation, as many of the genes and pathways have been identified. By
      contrast, relatively little is known about the genes and pathways involved in
      immunological tolerance to self-antigens. Here, we describe the challenges
      associated with a genomewide screen designed at identifying new immune regulatory
      genes that uses a model of organ-specific autoimmunity leading to type 1
      diabetes. The successful propagation and identification of the new gene variants
      will shed light on the various developmental checkpoints in lymphocyte
      development that are crucial for establishing tolerance to self-antigens.

PMID- 16623761
TI  - The plasticity of immunoglobulin gene systems in evolution.
AB  - The mechanism of recombination-activating gene (RAG)-mediated rearrangement
      exists in all jawed vertebrates, but the organization and structure of
      immunoglobulin (Ig) genes, as they differ in fish and among fish species, reveal
      their capability for rapid evolution. In systems where there can exist 100 Ig
      loci, exon restructuring and sequence changes of the constant regions led to
      divergence of effector functions. Recombination among these loci created hybrid
      genes, the strangest of which encode variable (V) regions that function as part
      of secreted molecules and, as the result of an ancient translocation, are also
      grafted onto the T-cell receptor. Genomic changes in V-gene structure, created by
      RAG recombinase acting on germline recombination signal sequences, led variously
      to the generation of fixed receptor specificities, pseudogene templates for gene
      conversion, and ultimately to Ig sequences that evolved away from Ig function.
      The presence of so many Ig loci in fishes raises interesting questions not only
      as to how their regulation is achieved but also how successive whole-locus
      duplications are accommodated by a system whose function in other vertebrates is
      based on clonal antigen receptor expression.

PMID- 16623763
TI  - Identifying susceptibility genes for immunological disorders: patterns, power,
      and proof.
AB  - There is a genetic basis to the most common immune-mediated diseases. Identifying
      disease susceptibility genes, however, has been a challenge. Only a few genes
      have been consistently replicated across multiple studies. These convincing
      examples provide insight into a genetic approach to common immune diseases as
      well as insight into disease pathogenesis. Here, we discuss several important
      concepts of a genetic study -- patterns, power, and proof -- and why these are
      germane in testing inherited variation for influence on disease. Recent
      developments in the fields of human genetics and genomics are overcoming
      limitations within the field, and we anticipate many exciting discoveries in the
      near future.

PMID- 16623764
TI  - A shared gene-expression signature in innate-like lymphocytes.
AB  - Innate and adaptive immunities are the two major arms of the immune system, which
      rely on distinct cell types. These cells can be distinguished not only by the
      source of diversity for non-self recognition, of germline or somatic origin, but
      also by their localization and the pattern and rates of response after encounter
      of antigenic triggers. In addition, subsets of lymphocytes exist whose receptors
      require rearrangement but result in semi-invariant structures with a high degree
      of self-specificity. We hypothesized that these innate-like lymphocytes might
      share a common gene transcription signature that relates them to classic members
      of the innate immune system. This relationship was first observed in agonist
      induced CD8alphaalpha T cells in fetal/neonatal thymus. We then asked whether
      this notion could be extended to other innate-like lymphocytes, by comparison of
      gene expression profiles of innate-like lymphocytes and closely paired adaptive
      system counterparts (NKT versus CD4T, CD8alphaalphaT versus CD8alphabetaT, and B1
      versus B2). A statistically significant 'innate signature' indeed was distilled.
      Particularly intriguing was the high representation of interferon-inducible
      guanosine triphophatases crucial for resistance against intracellular pathogens
      and of small G proteins involved in intracellular vacuole maturation and
      trafficking. Overall, this combined expression pattern can be designated as an
      innate signature among lymphocytes.

PMID- 16623765
TI  - A library of gene expression signatures to illuminate normal and pathological
      lymphoid biology.
AB  - Genomics has provided a lever to pry open lymphoid cells and examine their
      regulatory biology. The large body of available gene expression data has also
      allowed us to define the of coordinately expressed genes, termed gene expression
      signatures, which characterize the states of cellular physiology that reflect
      cellular differentiation, activation of signaling pathways, and the action of
      transcription factors. Gene expression signatures that reflect the action of
      individual transcription factors can be defined by perturbing transcription
      factor function using RNA interference (RNAi), small-molecule inhibition, and
      dominant-negative approaches. We have used this methodology to define gene
      expression signatures of various transcription factors controlling B-cell
      differentiation and activation, including BCL-6, B lymphocyte-induced maturation
      protein-1 (Blimp-1), X-box binding protein-1 (XBP1), nuclear factor-kappaB (NF
      kappaB), and c-myc. We have also curated a wide variety of gene expression
      signatures from the literature and assembled these into a signature database.
      Statistical methods can define whether any signature in this database is
      differentially expressed in independent biological samples, an approach we have
      used to gain mechanistic insights into the origin and clinical behavior of B-cell
      lymphomas. We also discuss the use of genomic-scale RNAi libraries to identify
      genes and pathways that may serve as therapeutic targets in B-cell malignancies.

PMID- 16623767
TI  - Transcriptional basis of lymphocyte tolerance.
AB  - Signaling through lymphocyte antigen receptors has the potential to initiate
      several distinct outcomes: proliferation, differentiation, apoptosis, or
      functional unresponsiveness. Expansion and differentiation of effector T cells is
      required for defense against foreign antigens, whereas functional
      unresponsiveness, termed anergy, is a cell-intrinsic mechanism that contributes
      to peripheral self-tolerance. Other mechanisms of peripheral tolerance include
      the 'dominant' tolerance imposed by regulatory T cells and immunosuppression
      mediated by interleukin-10 and transforming growth factor-beta. T- and B-cell
      antigen receptor ligation induces an increase in intracellular calcium levels as
      well as activating additional signaling pathways that are further potentiated by
      costimulatory receptors. In this review, we argue that cell-intrinsic programs of
      peripheral anergy and tolerance are imposed by sustained calcium signaling in
      lymphocytes. We address in particular the role of the calcium-dependent
      transcription factor nuclear factor for activation of T cells, which is activated
      by antigen receptor stimulation and, depending on the presence or absence of
      input from its transcriptional partner, activator protein-1, dictates two
      distinct transcriptional programs: activation or tolerance.

PMID- 16623766
TI  - Microarray-based understanding of normal and malignant plasma cells.
AB  - Plasma cells (PCs) develop from B lymphocytes following stimulation by antigen
      and express a genetic program aimed at the synthesis of immunoglobulins. This
      program includes the induction of genes coding for transcription factors such as
      PRDM1, X-box-binding protein 1 and BHLHB3, cell-surface molecules such as
      CD138/syndecan-1, and for the unfolded protein response. We review how the
      microarray technology has recently contributed to the understanding of the
      biology of this rare but essential cell population and its transformation into
      premalignant and malignant PCs.

PMID- 16623768
TI  - Gene expression profiling in human autoimmunity.
AB  - Human autoimmune diseases are well suited for the application of gene expression
      profiling. Sampling of blood cells and target tissues has already revealed many
      important pathways contributing to this spectrum of disorders, and many
      commonalities are emerging. For instance, clinically distinct diseases such as
      systemic lupus erythematosus, Sjogren's syndrome, dermatomyositis, and psoriasis
      all show evidence for dysregulation of the type I interferon pathway. These data
      suggest that autoimmune diseases will eventually be categorized at the level of
      gene expression. This work has led to advances in our understanding of disease
      pathogenesis and in the future promises to facilitate assessments of disease
      activity and improve targeting of therapies. Here, we review the literature on
      gene profiling in human autoimmune diseases and provide perspective on the
      current state of the art.

PMID- 16623769
TI  - Chipping into the human genome: novel insights for transplantation.
AB  - High throughput, high density platforms for transcriptional, proteomic, and
      metabonomic analyses are opening new doors for improving our understanding of the
      complexity and redundancy of the immune system in the interplay of the innate and
      allo-immune responses in organ transplantation. New insights are being obtained
      into the possible discrepancies between the gold standard of tissue pathological
      diagnosis and clinical graft outcomes, as new transcriptional categories of
      transplant rejection evolve. The bystander effects of chronic immunosuppression
      underlying the complexities of graft dysfunction are beginning to be understood.
      Non-invasive mechanisms to monitor transplants, by following 'footprints' of
      biomarker sets that reflect the disease phenotype, are being pursued for their
      clinical application for direct patient care. Utilization of these same biomarker
      sets may also offer a unique means to titrate immunosuppression and predict
      specific graft dysfunction events prior to clinical decline, thus bringing in the
      potential to reduce patient morbidity from infection and malignancy, preserve
      graft integrity, and limit the progression of chronic graft injury.
      Bioinformatics support is integral to the unraveling of the mysteries of the
      human genome, proteome, and metabolome in disease and in health.

PMID- 16623770
TI  - Use of baculovirus MHC/peptide display libraries to characterize T-cell receptor
      ligands.
AB  - Peptide/protein display libraries are powerful tools for identifying and
      manipulating receptor/ligand pairs. While the large size of bacterial phage
      display libraries has made them the platform of choice in many applications,
      often considerable engineering has been required to achieve display of properly
      folded and active eukaryotic proteins, such as antibodies. This problem has been
      partially solved in several eukaryotic display systems, e.g. using yeast or
      retroviruses, but these systems have their own limitations. Recently, baculovirus
      has been developed as a display system using the virus itself or infected insect
      cells as the display platform. Here, we review the development and use of
      baculovirus-infected cells as a platform for display libraries of peptides bound
      to major histocompatibility complex (MHC) class I (MHCI) or class II (MHCII). We
      have used fluorescent multimeric soluble T-cell receptors (TCRs) to screen these
      libraries and to identify peptide antigen mimotopes. We also present some
      improvements to this system that allow very large libraries to be constructed and
      screened. We have used these libraries to examine the role of MHCII-bound
      peptides in the presentation of the staphylococcal enterotoxin A (SEA) and to
      manipulate an MHCI tumor-associated antigen.

PMID- 16623771
TI  - Circuitry of nuclear factor kappaB signaling.
AB  - Over the past few years, the transcription factor nuclear factor (NF)-kappaB and
      the proteins that regulate it have emerged as a signaling system of pre-eminent
      importance in human physiology and in an increasing number of pathologies. While
      NF-kappaB is present in all differentiated cell types, its discovery and early
      characterization were rooted in understanding B-cell biology. Significant
      research efforts over two decades have yielded a large body of literature devoted
      to understanding NF-kappaB's functioning in the immune system. NF-kappaB has been
      found to play roles in many different compartments of the immune system during
      differentiation of immune cells and development of lymphoid organs and during
      immune activation. NF-kappaB is the nuclear effector of signaling pathways
      emanating from many receptors, including those of the inflammatory tumor necrosis
      factor and Toll-like receptor superfamilies. With this review, we hope to provide
      historical context and summarize the diverse physiological functions of NF-kappaB
      in the immune system before focusing on recent advances in elucidating the
      molecular mechanisms that mediate cell type-specific and stimulus-specific
      functions of this pleiotropic signaling system. Understanding the genetic
      regulatory circuitry of NF-kappaB functionalities involves system-wide
      measurements, biophysical studies, and computational modeling.

PMID- 16623772
TI  - Charting protein complexes, signaling pathways, and networks in the immune
      system.
AB  - Systematic deciphering of protein-protein interactions has the potential to
      generate comprehensive and instructive signaling networks and to fuel new
      therapeutic and diagnostic strategies. Here, we describe how recent advances in
      high-throughput proteomic technologies, involving biochemical purification
      methods and mass spectrometry analysis, can be applied systematically to the
      characterization of protein complexes and the computation of molecular networks.
      The networks obtained form the basis for further functional analyses, such as
      knockdown by RNA interference, ultimately leading to the identification of nodes
      that represent candidate targets for pharmacological exploitation. No individual
      experimental approach can accurately elucidate all critical modulatory components
      and biological aspects of a signaling network. Such functionally annotated
      protein-protein interaction networks, however, represent an ideal platform for
      the integration of additional datasets. By providing links between molecules,
      they also provide links to all previous observations associated with these
      molecules, be they of genetic, pharmacological, or other origin. As exemplified
      here by the analysis of the tumor necrosis factor (TNF)-alpha/nuclear factor
      kappaB (NF-kappaB) signaling pathway, the approach is applicable to any mammalian
      cellular signaling pathway in the immune system.

PMID- 16623773
TI  - Phospho-proteomic immune analysis by flow cytometry: from mechanism to
      translational medicine at the single-cell level.
AB  - Understanding a molecular basis for cellular function is a common goal of
      biomedicine. The complex and dynamic cellular processes underlying physiological
      processes become subtly or grossly perturbed in human disease. A primary
      objective is to demystify this complexity by creating and establishing relevant
      model systems to study important aspects of human disease. Although significant
      technological advancements over the last decade in both genomic and proteomic
      arenas have enabled progress, accessing the complexity of cellular interactions
      that occur in vivo has been a difficult arena in which to make progress.
      Moreover, there are extensive challenges in translating research tools to
      clinical applications. Flow cytometry, over the course of the last 40 years, has
      revolutionized the field of immunology, in both the basic science and clinical
      settings, as well as having been instrumental to new and exciting areas of
      discovery such as stem cell biology. Multiparameter machinery and systems exist
      now to access the heterogeneity of cellular subsets and enable phenotypic
      characterization and functional assays to be performed on material from both
      animal models and humans. This review focuses primarily on the development and
      application of using activation-state readouts of intracellular activity for
      phospho-epitopes. We present recent work on how a flow cytometric platform is
      used to obtain mechanistic insight into cellular processes as well as highlight
      the clinical applications that our laboratory has explored. Furthermore, this
      review discusses the challenges faced with processing high-content
      multidimensional and multivariate data sets. Flow cytometry, as a platform that
      is well situated in both the research and clinical settings, can contribute to
      drug discovery as well as having utility for both biomarker and patient
      stratification.

PMID- 16623774
TI  - A plaidoyer for 'systems immunology'.
AB  - A complete understanding of the immune system will ultimately require an
      integrated perspective on how genetic and epigenetic entities work together to
      produce the range of physiologic and pathologic behaviors characteristic of
      immune function. The immune network encompasses all of the connections and
      regulatory associations between individual cells and the sum of interactions
      between gene products within a cell. With 30,000+ protein-coding genes in a
      mammalian genome, further compounded by microRNAs and yet unrecognized layers of
      genetic controls, connecting the dots of this network is a monumental task. Over
      the past few years, high-throughput techniques have allowed a genome-scale view
      on cell states and cell- or system-level responses to perturbations. Here, we
      observe that after an early burst of enthusiasm, there has developed a distinct
      resistance to placing a high value on global genomic or proteomic analyses. Such
      reluctance has affected both the practice and the publication of immunological
      science, resulting in a substantial impediment to the advances in our
      understanding that such large-scale studies could potentially provide. We propose
      that distinct standards are needed for validation, evaluation, and visualization
      of global analyses, such that in-depth descriptions of cellular responses may
      complement the gene/factor-centric approaches currently in favor.

PMID- 16623776
TI  - Ki67 staining pattern as a diagnostic tool in the evaluation of
      lymphoproliferative disorders.
AB  - AIMS: To evaluate a group of lymphoid proliferations using only Ki67-stained
      slides to determine the value of the pattern of proliferating cells in diagnosis.
      Ki67 immunohistochemistry allows evaluation of the distribution of proliferating
      cells in addition to simply determining the proliferation rate of cells. METHODS
      AND RESULTS: Three observers, using a Ki67-stained slide only, studied 149 cases
      from five diagnostic groupings: follicular hyperplasia, mixed pattern
      hyperplasia, localized Castleman's disease, follicular lymphoma and marginal zone
      lymphoma. The sensitivity for benign lesions varied from 94% to 97% among the
      three observers. Follicular lymphomas were recognized as neoplastic with a
      sensitivity of 96% and 100% by two of the observers. Marginal zone lymphoma was
      recognized as neoplastic in 67-73% of cases. CONCLUSIONS: The Ki67 stain alone is
      a powerful tool for distinguishing benign from malignant proliferations within
      the selected groups. Nuances and pitfalls in the interpretation of Ki67 staining
      pattern are discussed.

PMID- 16623775
TI  - Update on extranodal lymphomas. Conclusions of the Workshop held by the EAHP and
      the SH in Thessaloniki, Greece.
AB  - Classification and proper treatment of extranodal lymphoma is hindered by the
      diversity of lymphoma types and the relative rarity of many of these tumour
      types. In order to review controversial issues in extranodal lymphoma diagnosis,
      a joint Workshop of the European Haematopathology Association (EAHP) and the
      Society for Hematopathology (SH) was held, where 99 selected cases were reviewed
      and discussed. This Workshop summary is focused on the most controversial aspect
      of cutaneous B-cell lymphoma, other extranodal B-cell lymphomas, plasmablastic
      lymphoma and anaplastic large-cell lymphoma in extranodal sites, and makes
      practical recommendations about diagnosis and therapeutic approaches.

PMID- 16623777
TI  - Epstein-Barr viral infection in extranodal lymphoma of the head and neck:
      correlation with prognosis and response to treatment.
AB  - AIMS: To determine the prevalence of Epstein-Barr virus (EBV) infection in
      primary extranodal lymphoma of the head and neck (PELHN) in immunocompetent
      patients. PELHN represents 16.18% of all lymphoma diagnosed at the National
      Cancer Institute, Cairo. Although EBV infection is highly associated with
      lymphoma in immunocompromised patients, the situation in immunocompetent patients
      is still unclear. MATERIAL AND METHODS: The study included 50 PELHN (11 cases in
      the nose and paranasal sinuses, 11 in the nasopharynx, 13 in the tonsils, seven
      in the oropharynx and eight in the oral cavity), five reactive lymph nodes, 15
      normal nasopharyngeal tissue and 25 throat washes of healthy subjects from Egypt.
      Cases and controls were assessed for the presence of EBV by polymerase chain
      reaction (PCR) and in situ hybridization techniques, the presence of 30 base pair
      deletion of the LMP-1 (del-LMP1) gene and for the expression of p53, Ki67, bcl-2
      and Bax by immunohistochemistry. This was also correlated with the clinical
      outcome of patients. RESULTS: EBV was detected in 90% and 70% of the cases using
      EBER in situ hybridization and PCR, respectively. All cases of nasal type
      lymphoma were positive for EBV. del-LMP1 gene was detected in 24/35 of EBV+ cases
      (68.6%), whereas 11 cases had wild-type variant either alone or mixed with del
      LMP1. There was a significant difference in the frequency of del-LMP1 between
      lymphoma and normal tissues. Overexpression of Ki67, p53 and bcl-2 was detected
      in 78.1%, 62.5% and 20% of cases, whereas loss of Bax was detected in 18% of the
      cases. Multivariate analysis showed that only p53 overexpression, del-LMP1
      variant and advanced disease stage are independent prognostic factors.
      CONCLUSION: EBV infection is frequent in PELHN in Egypt. Possible pathogenic
      mechanisms involve deregulation of p53 and enhanced proliferation (as detected by
      high Ki67 index). The presence of del-LMP1 variants, p53 overexpression and
      advanced disease stage are poor prognostic factors associated with reduced
      survival and poor response to therapy.

PMID- 16623778
TI  - The prevalence and clinical implications of c-kit expression in plasma cell
      myeloma.
AB  - AIM: To evaluate the clinical implications of c-kit (CD117) expression in plasma
      cell myeloma (PCM). METHODS AND RESULTS: We first evaluated the reliability of
      immunohistochemistry in assessing c-kit expression by comparing the results with
      those obtained by flow cytometry and gene expression arrays in 22 PCM and in 10
      PCM cell lines. Immunohistochemical results showed a perfect concordance with
      those of flow cytometry; likewise, immunohistochemical and gene expression data
      were also concordant in all but one PCM and cell lines analysed. Then, we
      investigated the clinical implications of c-kit immunoreactivity in bone marrow
      biopsies of 85 PCM patients with a mean follow-up of 41 months. C-kit
      immunoreactivity was detected in 24 (28.2%) of the 85 cases and it was
      significantly associated with a high microvessel density, but not with
      traditional clinicopathological characteristics or with survival. CONCLUSIONS:
      Our findings suggest that immunohistochemistry is a reliable indicator of c-kit
      gene expression and reinforce the notion that approximately one-third of PCM
      express high levels of c-kit. The lack of association with traditional
      clinicopathological parameters and patient survival suggests that c-kit
      expression may not be an adjunct in predicting the clinical course of the
      disease.

PMID- 16623779
TI  - Schwannoma of the gastrointestinal tract: a clinicopathological,
      immunohistochemical and ultrastructural study of 33 cases.
AB  - AIMS: Thirty-three cases of gastrointestinal schwannomas were analysed to
      elucidate their peculiar clinicopathological, immunohistochemical and
      ultrastructural features. METHODS AND RESULTS: The patients were 16 men and 17
      women, whose ages ranged from 27 to 81 years (median 52.6 years). Tumour size
      ranged from 10 to 120 mm in diameter. Follow-up in 23 cases from 6 months to 13
      years showed no recurrences or metastases. Microscopically, all tumours were
      composed of spindle cells with focal epithelioid cells in four cases. In all
      cases except one, there were peripheral cuff-like lymphoid aggregates.
      Immunohistochemically, tumours were strongly positive for S100 protein and
      vimentin, the tumours were variably positive for nestin (78.8%, 26/33) and glial
      fibrillary acidic protein (63.6%, 21/33), three tumours had CD34+ cells, but all
      were negative for CD117, alpha-smooth muscle actin and desmin. Ultrastructurally,
      the tumours were composed of elongated spindle shaped cells with prominent
      parallel membranous structures. CONCLUSIONS: Gastrointestinal schwannomas have
      characteristic histological features, especially the presence of a lymphoid cuff,
      that are different from their soft tissue and central nervous system
      counterparts. Gastrointestinal tract schwannomas behave in a benign fashion.

PMID- 16623780
TI  - Oval cells in hepatitis B virus-positive and hepatitis C virus-positive liver
      cirrhosis: histological and ultrastructural study.
AB  - AIMS: It is still not clear whether oval cells demonstrate diverse morphology,
      immunophenotype or quantity in different human liver diseases. The aim of this
      study was to investigate these differences in hepatitis B virus (HBV)-positive
      and hepatitis C virus (HCV)-positive human liver cirrhosis (HLC). METHODS AND
      RESULTS: Thirty-eight cases of HBV+ HLC and 32 cases of HCV+ HLC were
      investigated by light microscopy and immunohistochemistry for Hepatocyte, CK19,
      stem cell factor (SCF) and CD34. Five cases were also examined by transmission
      electron microscopy. Oval cells of similar morphology could be found in
      proliferating bile ductules in both groups. These cells coexpressed CK19 and
      Hepatocyte, but did not express SCF or CD34. Some of these cells exhibited a
      trend towards differentiation. There was no difference in the amount of oval
      cells between the two groups. The oval cell number was found to increase
      significantly with the progression of inflammation. A similar stem-like cell was
      not seen in the normal liver. CONCLUSIONS: There are bipotential oval cells in
      both HBV+ and HCV+ HLC. The lack of difference in oval cells between the two
      groups suggests that they might play a similar biological role in the
      histogenesis of different liver diseases.

PMID- 16623781
TI  - A new vision of tubular and tubulo-lobular carcinomas of the breast, as revealed
      by 3-D modelling.
AB  - AIMS: To reveal architectural structure and growth patterns of tubular carcinomas
      (TC) and tubulo-lobular carcinomas (TLC) of the breast. METHODS AND RESULTS: We
      studied a series of 20 pure TC and 22 TLC, evaluating the architectural features
      of the two entities by bi-dimensional microscopy and by 3-D modelling. We traced
      the spatial organization of three TCs and three TLCs on serial sections using
      AE1/AE3 cytokeratin as a marker of the epithelial structures and reconstructed 3
      D models of each histological type. The analysis of TC on serial cytokeratin
      stained sections showed that the form of the 'tubules' was related to the plane
      of sectioning and that often they were tear-drop shaped, with a final tail of
      single cells connecting them together. 3-D models corresponded to a necklace
      appearance and the tubules of TC appeared as blebs bridging through solid cords
      to other blebs. In TLC the structure was similar, but the connecting single-cell
      files were usually longer. Both TC and TLC showed similar E-cadherin positivity
      and an indolent clinical behaviour. CONCLUSIONS: TC and TLC share the same
      architectural and growth patterns and ultimately seem to represent variants of
      the same tumour type.

PMID- 16623782
TI  - Uterine leiomyoma versus leiomyosarcoma: a new attempt at differential diagnosis
      based on their cellular characteristics.
AB  - AIM: To differentiate uterine leiomyoma (LM) with 'pseudosarcomatous' features
      from leiomyosarcoma (LMS). We hypothesized that because pseudosarcomatous LM is
      only a benign variant of conventional LM, it may have some characteristics
      different from LMS. METHODS AND RESULTS: Fourteen uterine smooth muscle tumours,
      which had been diagnosed as LMS previously, were reviewed and divided into
      adverse outcome (true LMS; seven cases) and excellent outcome groups (presumed
      pseudosarcomatous LM; seven cases) based on their clinical course. The tumours of
      the adverse outcome group were composed of rather uniform long spindle cells
      similar to those of leiomyosarcoma arising from the soft tissue. All tumours in
      this group had coagulative necrosis and all but one case were diagnosed
      preoperatively as malignant. In contrast, the tumours of the excellent outcome
      group showed significant histological diversity both between tumours and also in
      the same tumour and areas indistinguishable from conventional LM were often seen.
      All the tumours of this group were diagnosed preoperatively as benign.
      Immunohistochemically, all tumours of the excellent outcome group expressed
      progesterone receptor, often intensely, and also frequently expressed oestrogen
      receptor. In contrast, all the tumours of the adverse outcome group lacked them
      completely. CONCLUSION: Pseudosarcomatous LM has characteristics useful for
      differentiating it from LMS, which are common in conventional LM.

PMID- 16623783
TI  - ALK expression in pseudosarcomatous myofibroblastic proliferations of the
      genitourinary tract.
AB  - AIMS: Pseudosarcomatous myofibroblastic proliferation of the genitourinary tract
      is rare and may develop after trauma or spontaneously. The aim of this study was
      to characterize further the clinicopathological features of these lesions and to
      examine their relationship to inflammatory myofibroblastic tumour (IMT). METHODS
      AND RESULTS: Twenty-seven cases of pseudosarcomatous myofibroblastic
      proliferation were analysed. There were seven males and 20 females; median age
      was 37 years (range 16-88). Most lesions were from the bladder (n = 21), while
      others were in the urethra, vulva, vagina, rectum and retrovesical space. Median
      tumour size was 30 mm (range 6-120 mm). Seven cases (25%) had a history of prior
      trauma or surgery. Three cases recurred locally but not destructively. The
      tumours had fasciitis-like features including bland spindle cells with evenly
      distributed chromatin, admixed inflammatory cells (mainly lymphocytes) and often
      a myxoid stroma. Immunohistochemistry showed positivity for smooth muscle actin
      in 14/20 cases, keratin in 8/19, desmin in 7/20 and anaplastic lymphoma kinase
      (ALK) in 10/21 cases. Fluorescent in situ hybridization was performed in six ALK+
      cases; all were negative for ALK gene rearrangement. CONCLUSIONS:
      Pseudosarcomatous myofibroblastic proliferations of the genitourinary tract may
      show ALK immunopositivity but do not show consistent ALK rearrangement. Given
      subtle morphological differences and more consistently benign behaviour, their
      relationship to inflammatory myofibroblastic tumour at other sites remains
      uncertain.

PMID- 16623784
TI  - High promoter hypermethylation frequency of p14/ARF in supratentorial PNET but
      not in medulloblastoma.
AB  - AIMS: Medulloblastoma (MB) is the most common primitive neuroectodermal tumour
      (PNET) of the central nervous system. Although supratentorial PNET (sPNET) and MB
      are histologically similar, their clinical behaviour differs, sPNET being more
      aggressive than MB. The aim of this study was to determine whether sPNET and MB
      are genetically different entities. METHODS AND RESULTS: We investigated 32 PNET
      primary tumour samples (23 MB and nine sPNET) and four PNET cell lines, for the
      presence of CDKN2A homozygous deletions at exon 1-alpha of p16/INK4 and exon 1
      beta of p14/ARF, and promoter hypermethylation of both genes. No homozygous
      deletion of either p16/INK4 or p14/ARF was demonstrated in any of the PNET
      primary tumour samples. Methylation of p16/INK4 was found in one of six sPNET and
      in one of 23 MB, while p14/ARF methylation was observed in three of six sPNET and
      in three of 21 MB. No methylation of p16/INK4 or p14/ARF was found in any of the
      PNET cell lines analysed. The three MB cell lines did not show p16/INK4
      expression, and only the MB Daoy cell line (homozygously deleted at CDKN2A)
      presented loss of p14/ARF expression. CONCLUSIONS: Our results in this limited
      series of central PNET show that p14/ARF is frequently involved in PNET
      carcinogenesis, with a higher frequency, but not statistically significant, for
      sPNET than for MB.

PMID- 16623785
TI  - The distribution of matrix metalloproteinases and tissue inhibitors of
      metalloproteinases in the lungs of congenital diaphragmatic hernia patients and
      age-matched controls.
AB  - AIMS: In congenital diaphragmatic hernia (CDH), the pathogenesis of abnormal
      pulmonary morphology is still incompletely understood. Matrix metalloproteinases
      (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are known to play an
      important role in the turnover of the extracellular matrix (ECM) during
      development and in remodelling of tissue. The aim of this study was to
      investigate differences in the expression of MMPs and TIMPs between CDH lungs and
      controls, against the background of the abnormal pulmonary vasculature in CDH.
      METHODS: We studied 12 lungs of term CDH patients who died < 24 h after birth and
      11 normal age-matched control lungs, by immunohistochemistry with antibodies
      against human MMP-1, -2, -9, TIMP-1 and -2. RESULTS: There was a clear increase
      in the number of MMP-1-reactive capillaries and fibroblasts in CDH lungs compared
      with controls. In contrast, TIMP-2 reactivity in these structures was decreased
      in CDH lungs. The arterial endothelium and medial smooth muscle expressed MMP-2, 
      9 and TIMP-2 in both CDH and control lungs. In small arteries (< 100 microm in
      diameter), the positive surface area of MMP-2, -9 and TIMP-2 was significantly
      larger in CDH lungs than in controls. There was no difference in the distribution
      and expression of TIMP-1 between CDH lungs and normal controls. CONCLUSION: The
      differences in staining pattern of MMPs and TIMPs between normal and CDH lungs
      suggest that these enzymes might play a role in the abnormal remodelling of the
      interstitium and the pulmonary arteries in CDH lungs. This could contribute to
      our understanding of the abnormal lung morphology and the occurrence of pulmonary
      hypertension, which forms one of the major obstacles to the successful treatment
      of these patients.

PMID- 16623786
TI  - Pulmonary involvement by Niemann-Pick disease. A report of six cases.
AB  - AIMS: Although pulmonary involvement is a known cause of morbidity in Niemann
      Pick disease, histological features in the lung are not well characterized. The
      purpose of this study is to document the histological features seen in pulmonary
      involvement by types B and C Niemann-Pick disease and to correlate them with
      clinical and imaging data. METHODS AND RESULTS: Surgical lung biopsies from six
      patients (four with type B and two with type C disease) were reviewed and all
      showed diffuse endogenous lipid pneumonia, with lesser involvement of the
      interstitium by fibrosis and foamy macrophage accumulation. In type B disease
      only, there was also fine cytoplasmic vacuolation within the cytoplasm of
      ciliated epithelial cells. Neither disease showed foamy changes within
      pneumocytes. One patient had a bronchial cast removed on whole lung lavage.
      Electron microscopy showed abnormal lamellar inclusions within lysosomes of
      affected cells in type B disease. In patients with type C disease, biopsies were
      undertaken as part of investigations into acute respiratory failure in the
      context of multiorgan systemic presentation. Three patients with type B disease
      had clinical disease limited to the lung, all adults (mean age of 40 years) with
      unexplained diffuse parenchymal lung disease and mainly ground-glass shadowing on
      high-resolution computed tomography. CONCLUSIONS: Niemann-Pick disease should be
      considered for any patient with unexplained diffuse endogenous lipid pneumonia,
      even when disease is limited to the lungs and presentation is during adulthood.

PMID- 16623788
TI  - Incidence of HPV in primary and metastatic squamous cell carcinomas of the
      aerodigestive tract: implications for the establishment of clonal relationships.

PMID- 16623789
TI  - An alternative method of dissecting mastectomy specimens.

PMID- 16623790
TI  - Atypical polypoid adenomyoma: a systematic review of the English literature.

PMID- 16623791
TI  - Lack of pericryptal fibroblastic cells adjacent to intestinal epithelial
      metaplastic gastric glands.

PMID- 16623792
TI  - Expression of CD73 and its ecto-5'-nucleotidase activity are elevated in
      papillary thyroid carcinomas.

PMID- 16623793
TI  - SEL1L expression in prostatic intraepithelial neoplasia and adenocarcinoma: an
      immunohistochemical study.

PMID- 16623794
TI  - Inflammatory pseudotumour of the testis in an HIV patient.

PMID- 16623795
TI  - Desmoplastic infantile ganglioglioma. Morphological, immunohistochemical and
      genetic features.

PMID- 16623796
TI  - Composite mantle-cell lymphoma and classical Hodgkin lymphoma.

PMID- 16623797
TI  - Intracellular spread of Ewing's sarcoma within skeletal muscle fibres: is there a
      role for cytotoxic tumour-infiltrating lymphocytes?

PMID- 16623798
TI  - Xenotransplantation literature update November-December 2005.

PMID- 16623800
TI  - Heart transplantation across antibodies against human leukocyte antigen and ABO
      post-transplant follow-up of donor reactive antibodies.
AB  - BACKGROUND: We have successfully performed heart transplantation despite the most
      unfavourable risk factors for graft and patient survival: the presence of a high
      level of antibodies (Abs) against the donor's human leukocyte antigens (HLA)
      class I/II and blood group A1 antigens. The present study concerns post
      transplant follow-up and characterization of donor reactive antibodies (DRA).
      METHODS: Pre-transplant treatment consisted of mycophenolate mofetil (MMF),
      prednisolone, tacrolimus, intravenous immunoglobulin (IVIG), rituximab, protein-A
      immunoadsorption (PAIA) and per-operative plasma exchange. A standard triple-drug
      immunosuppressive protocol was used post-operatively. Abs were analyzed by the
      complement dependent cytotoxicity (CDC) test against donor and panel B/T cells
      and by flow cytometry (FlowPRA tests detecting isolated HLA class I/II antigens).
      Abs against the donor's erythrocytes were analyzed using a standard direct
      agglutination test for immunoglobulin M (IgM) Abs and a Bio-Rad AHG gel card test
      detecting IgG Abs and C3d. RESULTS: Pre-transplant treatment reduced Ab titers
      against the donor's lymphocytes from 128 to 16 and against the donor's blood
      group A1 antigen from 256 to 0. The patient was emergently transplanted with a
      heart from a blood group incompatible donor (A1 secretor to O). No hyperacute
      rejection was seen. DRA were present against all mismatched HLA class I and class
      II antigens at the time of transplantation; two of these DRA Abs disappeared
      within the first year post-transplant (anti-B62 and anti-DR4), one showed
      weakened reactivity (anti-A24) and one is still strongly reactive (anti-DQ3). The
      donor-specific CDC cross-match is still positive (titers 2 to 8). The level of
      panel reactive antibodies (PRA) remained unchanged from 6 months on post
      transplant. Rising anti-A1 blood group Abs preceded the second rejection and were
      adsorbed by two blood group specific immunoadsorptions (Glycosorb)-ABO) and
      remained at a low level. IgM anti-A1 blood group Abs disappeared at 1 yr post
      transplant and IgG Abs are still reactive with blood group A1 erythrocytes but at
      low titers (1 to 2). CONCLUSIONS: The patient is clinically well 2 years after
      heart transplantation despite the constant persistence of donor reactive IgG Abs
      against blood group A1 and HLA-DQ antigens. The reactivity of DRA against other
      mismatched HLA antigens disappeared or weakened during the follow-up period.

PMID- 16623801
TI  - The Stockholm experience with ABO-incompatible kidney transplantations without
      splenectomy.
AB  - BACKGROUND: ABO-incompatible kidney transplantations have previously only been
      performed after several pre-operative sessions of plasmapheresis followed by
      splenectomy, and with the conventional triple-drug immunosuppressive protocol
      being reinforced with anti-lymphocyte globulin and B-cell-specific drugs. We have
      designed a protocol without splenectomy, based on antigen-specific
      immunoadsorption, rituximab and a conventional triple-drug immunosuppressive
      protocol. METHODS: The protocol called for a 1-month pre-transplantation
      conditioning period, starting with one dosage of rituximab and followed by full
      dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific
      immunoadsorption was performed on pre-transplantation days -6, -5, -2 and -1.
      After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was
      administered. Postoperatively, three more apheresis sessions were given every
      third day. RESULTS: Twenty-one patients have received transplants with this
      protocol. The ABO-antibodies (Abs) were readily removed by the antigen-specific
      immunoadsorption and were kept at a low level post-transplantation by further
      adsorptions. There were no side effects, and all but one patient have normal
      renal transplant function. CONCLUSIONS: We conclude that after one infusion each
      of rituximab and IVIG, and antigen-specific immunoadsorption, blood-group
      incompatible renal transplantations can be performed with standard
      immunosuppression and without splenectomy, and with excellent short- and long
      term results.

PMID- 16623802
TI  - ABO-incompatible kidney transplantation using antigen-specific immunoadsorption
      and rituximab: a single center experience.
AB  - BACKGROUND: For years ABO-incompatible kidney transplantations were
      preferentially performed in Japanese centers. In order to overcome the increased
      risk of humoral rejections, patients were treated with multiple sessions of
      plasmapheresis, intensified immunosuppressive therapy and splenectomy before
      transplantation. Despite good long-term results regarding patient and organ
      survival rates, increased morbidity during the early post-transplant period
      prevented a broad application of this method. Recently, a new protocol including
      the anti-CD20-antibody (Ab) rituximab and blood group-specific immunoadsorption
      instead of splenectomy and plasmapheresis was published with excellent short-term
      results. METHODS: From April 2004 to September 2005, 11 patients were prepared
      for ABO-incompatible transplantation. All patients received 375 mg/m2 rituximab
      intravenous 3 to 4 weeks before transplantation. Immunosuppressive therapy
      consisted of tacrolimus, mycophenolate mofetil and prednisone and was started at
      least 7 days before transplantation. Intravenous immunoglobulins (0.5 g/kg) were
      administered the day before transplantation. Immunoglobulin G (IgG)-anti-A or -B
      Ab titers before starting immunoadsorption treatment ranged between 1 : 4 and 1 :
      1024. Immunoadsorption treatment was started in parallel with immunosuppressive
      medication and was continued until the anti-A or anti -B Ab titers (IgG and IgM)
      were lowered to the aimed pre-transplant threshold of <1 : 8. During the early
      postoperative period, additional immunoadsorption treatments were performed, if
      the titers increased again above 1 : 8 (days 0 to 7) or 1 : 16 (days 8 to 14),
      respectively. RESULTS: Transplantation could be conducted in eight of 11 patients
      (two females, six males, mean recipient age 52+/-11 yr). The mean follow-up was
      7.0 months (range 4 to 17). The blood group constellation was A1 to 0 in four
      cases, A2 to 0 in two cases, B to A in one case, and A1 to B in another case,
      respectively. On average, each patient received seven immunoadsorption
      treatments. All transplants showed primary function and no humoral rejections
      occurred. Three of our 11 patients showed rapid increases of isoagglutinin titers
      after each immunoadsorption treatment and thus could not be transplanted. One
      patient died 4 months after transplantation with a functioning graft due to
      sepsis secondary to pseudomembranous enterocolitis. The mean creatinine value of
      the remaining seven patients now is 1.6 mg/dl. SUMMARY: The use of antigen
      specific immunoadsorption and an immunosuppressive regimen consisting of a
      conventional triple immunosuppressive therapy has shown excellent short-term
      results. The immunoadsorption treatment using antigen-specific columns is highly
      effective and even patients with high isoagglutinin titers can be transplanted.
      This protocol is an option for end-stage renal disease patients who have no blood
      group-compatible donor.

PMID- 16623803
TI  - Pinpoint targeted immunosuppression: anti-CD20/MMF desensitization with anti-CD25
      in successful ABO-incompatible kidney transplantation without splenectomy.
AB  - BACKGROUND: In Japan, ABO-incompatible (ABO-I) kidney transplantation began in
      1989; these transplantations have flourished because of the lack of cadaveric
      donors, and more than 600 cases were performed up to 2004. Splenectomy has been
      considered to be necessary for successful ABO-I kidney transplantation, and the
      majority of pre-conditioning protocols include splenectomy in Japan. However, we
      have lost some grafts due to antibody-mediated rejection (AMR) accompanying
      explosive elevation of anti-A/B antibody (Ab) titer even though the patients had
      a low pre-operative Ab titer. PATIENTS AND METHODS: We utilized two doses of anti
      CD20, rituximab, simply combined with mycophenolate mofetil (MMF)/low-dose
      steroid desensitization started 1 month before surgery in ABO-I kidney
      transplantation. Two sessions of pre-operative Ab removal by double filtration
      plasmapheresis or plasma exchange were carried out. We performed six ABO-I kidney
      transplantations without splenectomy. Anti-A/B Ab titers were more than 16 to 32
      times before treatment. We did not plan any post-operative repeated Ab removal or
      intravenous immunoglobulin G (IVIG). RESULTS: Pre-operative anti-A/B Ab titers
      were successfully reduced to less than eight times in all cases. Except for one
      case in which we had to remove the graft due to aspiration pneumonia and
      methicillin-resistant staphylococcus epidermidis (MRSE) sepsis, the other five
      cases did not experience antibody-mediated rejection (AMR). An additional session
      of post-operative Ab removal and/or IVIG was not necessary. In all patients, B
      cells (CD19+, CD20+, CD21+) and activated T cells (CD25+) were selectively
      suppressed, although CD3+, CD4+ and CD8+ cell populations remained stable, thus
      we call our protocol "pinpoint targeted immunosuppression." Plasma immunoglobulin
      level was also successfully suppressed, especially after 6 weeks of surgery.
      CONCLUSION: Anti-CD20/MMF desensitization is safe and allows successful ABO-I
      kidney transplantation without splenectomy.

PMID- 16623804
TI  - Present status of ABO-incompatible kidney transplantation in Japan.
AB  - BACKGROUND: We have been making continuous efforts in ABO-incompatible kidney
      transplantation since 1989 to expand the opportunities for kidney transplantation
      from living donors in Japan. PATIENTS AND METHOD: From the Japanese registry, we
      reviewed the long-term patient and graft survival of ABO-incompatible kidney
      transplantation. This survey focused on 564 patients who received ABO
      incompatible kidney grafts from January 1989 to December 2003 in whom monitoring
      follow-up could be achieved in 60 institutions all over Japan. The mean age of
      367 (65%) male and 197 (35%) female patients at surgery was 34.5 yr. Pre
      operative anti-A/B antibody (Ab) removal and splenectomy (n = 553, 98%) were
      routinely performed combined with triple or quadruple immunosuppression using
      calcinurine inhibitor (CNI), anti-metabolites and steroids with or without
      deoxyspurgualin (DSG) or anti-lymphocyte Abs. RESULTS: The overall patient
      survival rate at 1, 3, 5 and 10 yr after transplantation was 94, 91, 88 and 81%,
      with overall graft survival rates of 86, 82, 74 and 53%, respectively. The graft
      survival rate was significantly higher in patients aged 29 and younger compared
      with those aged 30 and older. Children aged 15 or younger in particular have
      shown excellent graft survival rates at 1, 3, 5 and 10 yr of 90, 90, 86 and 76%,
      respectively. Patients with anticoagulation therapy (n = 285) showed a
      significantly higher graft survival rate than those without anticoagulation (n =
      213), with 10-yr graft survival rates of 59 vs. 48%. There were no significant
      differences between A and B incompatibility with respect to clinical outcomes.
      There were also no significant difference in numbers of human leukocyte antigen
      mismatches, induction and maintenance CNI (cyclosporin A (CYA) vs. tacrolimus)
      and donor/recipient relationships with respect to the outcomes. We divided the
      patients into five groups according to the transplanted year periods. The outcome
      of the most recent 124 cases since 2001 had dramatically improved, with 2-yr
      graft survival of 94%, and there is a significant difference between the groups
      in 2001 onwards and the other four groups. CONCLUSION: This study confirms that
      the long-term outcome of ABO-incompatible living kidney transplantation is
      excellent and is similar to that of ABO-compatible cases. Recent data show that
      short-term graft survival has also improved. ABO-incompatible kidney
      transplantation is a radical, but safe and effective, treatment choice for end
      stage renal disease.

PMID- 16623805
TI  - First two ABO-incompatible living renal transplantations using splenectomy,
      rituximab, plasmapheresis and IVIG as a preconditioning regimen: a single center
      experience in the Balkans.
AB  - BACKGROUND: Due to the growing organ shortage in the Balkans and still
      underdeveloped cadaver transplantation, we started accepting living expanded
      criteria renal donors including elderly, marginal and unrelated donors (spouses,
      etc). The ABO-incompatible renal transplantation was initiated last year. The
      first two successful cases are presented. METHODS: A 40-yr-old mother (blood
      group A1B) and a 57-yr-old husband (blood group B) were considered as suitable
      donors for an 18-yr-old daughter (blood group B) and a 52-yr-old wife (blood
      group O). Both the recipients had a relatively long dialysis treatment before the
      surgery. The anti-A1 and anti-B titer of isoaglutinins was 1 : 64 in both the
      recipients before the procedure. A routine laparoscopic splenectomy was performed
      40 and 45 days before the transplantation, without any complications. In the 10
      days pre-conditioning period, rituximab was administered in a single dose of 375
      mg/m2. At the same time four to five plasmaphereses were performed to reduce the
      isoaglutinins to below 1 : 4. On the last night before the surgery intravenous
      immunoglobulin (IVIG) in a dose of 0.5 g/kg/bw was administered. Standard
      induction and maintenance therapy was introduced (Dacllizumab, CyA-Neoral, MMF
      and steroids) according to the accepted policy in our transplant center. The
      routine plasmaphereses were performed in the first 2 weeks after transplantation
      to keep the isoaglutinins titer below 1 : 8. RESULTS: Ten and 6 months after the
      surgery both recipients are doing well. Their graft function remains stable
      (actual serum creatinin 140 and 230 microm/L, respectively). In the 1 month
      protocol biopsy a subclinical cellular and mild vascular rejection occurred, and
      both recipients were treated by steroid pulse therapy. One to two additional
      plasmaphereses were performed. The regularly monitored anti-A1 and anti-B
      isoaglutinins titer was kept below 1 : 8 during a period of follow-up.
      CONCLUSION: The first short-term results fully justify the ABO-incompatible
      living renal transplantation. The authors consider ABO-incompatible
      transplantation as a safe and promising procedure which may, together with
      expanded criteria living donors, ameliorate the actual donor shortage in the
      region.

PMID- 16623806
TI  - Major ABO-incompatible hematopoietic stem cell transplantation: study of post
      transplant pure red cell aplasia and endothelial cell chimerism.
AB  - BACKGROUND: In contrast to human leukocyte antigen (HLA) matching, ABO-blood
      group incompatibility plays a minor role in the success of allogeneic
      hematopoietic stem cell transplantation (HSCT). Incompatible ABH histo-blood
      group antigens, expressed on recipient endothelial cells (EC) and donor erythroid
      progenitor cells, may represent targets for graft-versus-host disease (GVHD) and
      host-versus-graft reactions, respectively. The aims of the current study were to
      investigate: (1) red blood cell (RBC) engraftment and (2) EC chimerism as a
      potential result of replacement of recipient EC by donor bone marrow (BM)-derived
      EC in a patient following major ABO-incompatible (A to O) and gender-mismatched
      HSCT, who died at day 350 of severe acute GVHD. METHODS: Blood counts and anti
      A/B isoagglutinin titers were analyzed repeatedly. Heart and BM specimens were
      obtained at autopsy. The expression of ABH histo-blood group antigens was
      examined by immunhistochemistry, X/Y chromosomes were detected by chromogen in
      situ hybridization (CISH). RESULTS: RBC engraftment defined as appearance of 1%
      reticulocytes in the peripheral blood was delayed and correlated with anti-donor
      isoagglutinin titers. Circulating hematopoietic cells were exclusively of donor
      origin demonstrating full donor hematopoietic chimerism, whereas EC in heart and
      BM blood vessels were exclusively of the recipient type. CONCLUSIONS: Pure red
      cell aplasia (PRCA) after major ABO-incompatible HSCT was caused by anti-A/B
      isoagglutinins produced by recipient-type plasma cells. Using ABO and gender
      mismatch for discrimination, heart and BM blood vessels demonstrated no evidence
      for EC chimerism 11 months after ABO-incompatible HSCT. These findings suggest
      that EC replacement and chimerism do not represent major mechanisms responsible
      for tolerance induction after HSCT.

PMID- 16623807
TI  - ABO-incompatible kidney transplantation with anti-CD20 monoclonal antibodies,
      intravenous immunoglobulin and plasmapheresis without splenectomy: a case report.
AB  - A 24-yr-old man was admitted to our hospital for ABO-incompatible kidney
      transplantation. His blood type was O, and the donor's (his father's) blood type
      was B. The recipient had pancytopenia, splenomegaly, splenorenal shunts and
      esophageal varices due to congenital hepatic fibrosis. Therefore, if
      splenorectomy was performed, the blood pressure of the portal vein and the growth
      of esophageal varices were predicted. Eventually, in return for splenectomy, anti
      CD20 monoclonal antibodies (rituximab), intravenous immunoglobulin and
      plasmapheresis was performed for additional immunosuppression. Because of
      progression of pancytopenia, we had to decrease the dose of mycophenolate mofetil
      and gave up on using deoxyspagalin. Nevertheless the serum creatinine level
      decreased and remained in the 1.6 to 1.8 mg/dl range.

PMID- 16623808
TI  - A series of surveys on assay for anti-A/B antibody by Japanese ABO-incompatible
      Transplantation Committee.
AB  - BACKGROUND: The measurement of anti-blood groups A and B antibody (Ab) titers is
      considered to be important in ABO-incompatible transplantation. However, no
      standard method for quantitative determination has yet been established in Japan.
      Inter-examiner variability was likely because Ab titer was determined mainly by
      visual observation. In order to assess inter-institutional variation in the
      measurement of anti-A/B Ab titer, a series of surveys was conducted by the
      Japanese ABO-incompatible Transplantation Committee. METHODS AND RESULTS: In
      2003, the first national survey was conducted. Serum samples from six healthy
      volunteers with blood groups A (n = 2), B (n = 2) and O (n = 2) were sent to 29
      institutions and anti-A/B Ab titer was measured by their customary methods.
      Isohemagglutinin assay in serial-doubling dilutions of serum using a test tube
      was widely used in all institutions. Inter-institutional difference between
      maximum and minimum value reached as much as 32-fold in immunoglobulin M (IgM)
      and 256-fold in IgG. As detailed protocol for assay seemed to be different
      between institutions, we attempted to standardize the protocol based on the
      result of a questionnaire survey. In 2004, a second survey was conducted in the
      same manner as the previous one, except participation involved 38 institutions
      and the measurement was performed in a uniform way using a provisional standard
      protocol. Analysis of the survey revealed that intra-institutional variation was
      reduced to below eightfold, except that several institutions showed a large
      difference from the mean titer and required some guidance. CONCLUSIONS: A
      periodical quality control survey is considered necessary to improve the accuracy
      of measurement. Anti-A/B Ab titer would provide useful information towards the
      prediction of rejection and the indication of treatments such as (double
      filtration) plasmapheresis, splenectomy, anti-CD20 monoclonal antibody and
      intravenous immunoglobulin. Standardization of the assay for anti-A/B Ab titer is
      essential for the fulfillment of a precise multicenter study, which will
      elucidate the significance of the measurement of anti-A/B Ab titer.

PMID- 16623809
TI  - ABO-incompatible kidney transplantation of an 8-yr-old girl with donor/recipient
      constellation A1B/B.
AB  - BACKGROUND: Antigen-specific immunoadsorption combined with rituximab offers the
      possibility for ABO-incompatible kidney transplantation without splenectomy.
      PATIENT AND METHOD: An 8-year-old mentally retarded girl with steroid-resistant
      nephrotic syndrome and focal segmental glomerulosclerosis due to
      mitochondriopathy poorly tolerated hemodialysis. Paternal blood group A1B was
      incompatible with blood group B of the child. Therefore, we decided to perform
      the first ABO-incompatible renal transplantation in a child in Germany using
      antigen-specific immunoadsorption. Rituximab (1 x 375 mg/m2) was administered 2
      weeks before the first immunoadsorption (Glycosorb) ABO A-column). Triple-drug
      immunosuppression (tacrolimus, mycophenolate mofetil and prednisolone) was
      simultaneously started with immunoadsorption. Initial tacrolimus levels were
      targeted between 15 and 20 ng/ml. Before transplantation, six immunoadsorptions
      were applied on days -9, -7, -4, -3, -2 and -1. Intravenous immunoglobulin (0.5
      g/kg) was administered preoperatively. After transplantation, three
      immunoadsorptions were performed on days +4, +6 and +8. RESULTS: Before
      transplantation, antibody (Ab) titers against paternal erythrocytes (20 degrees
      C) were reduced from 1 : 64 to 1 : 4 by six antigen-specific immunoadsorptions.
      After transplantation, we performed three more immunoadsorptions and the Ab
      titers were stable between 1 : 1 and 1 : 8. One, 2 and 8 months later we observed
      increases in the Ab titer up to 1 : 32 requiring no change in immunosuppressive
      therapy. No side effects of immunoadsorption were observed. The girl had
      excellent initial graft function with a serum creatinine of 55 to 70 micromol/l.
      Two weeks after transplantation, graft biopsy showed no signs of rejection; there
      was focal positivity for C4d only. Twelve months after transplantation, renal
      function was stable, with a serum creatinine of 117 micromol/l. Episodes of
      rejection or severe infections were absent. CONCLUSION: ABO-incompatible
      transplantation using antigen-specific immunoadsorption and rituximab may serve
      as a suitable alternative for children urgently needing renal transplantation and
      missing a blood group-compatible donor.

PMID- 16623810
TI  - ABO-incompatible live donor renal transplantation using blood group A/B
      carbohydrate antigen immunoadsorption and anti-CD20 antibody treatment.
AB  - BACKGROUND: Blood group ABO-incompatible live donor (LD) renal transplantation
      may provide a significant source of organs. We report the results of our first 14
      cases of ABO-incompatible LD renal transplantation using specific anti-A/B
      antibody (Ab) immunoadsorption (IA) and anti-CD20 monoclonal Ab (mAb) treatment.
      PATIENTS AND TREATMENT PROTOCOL: Recipients were blood group O (n = 12), A (n =
      1) and B (n = 1). Donors were A1 (n = 2), A2 (n = 3), A2B (n = 1) and B (n = 8),
      and all were secretor positive. Anti-human leukocyte antigen (HLA) Ab panel
      reactivity was negative in all recipients except one. All recipients were pre
      treated with 3 to 6 IA sessions, using A or B carbohydrate antigen columns, until
      their anti-A1/B RBC panel indirect antiglobulin test (IAT) titers were < or =8.
      CDC crossmatch was negative in all cases. Recipients received preoperative
      mycophenolic acid, and steroids/tacrolimus were started at transplantation. No
      splenectomy was performed. Eight recipients received one dose of anti-CD20 mAb
      (rituximab, 375 mg/m2) pre-operatively and 11 recipients had postoperative
      protocol IA. RESULTS: In the initial protocol, anti-CD20 mAbs were used only for
      recipients receiving A1 grafts. One B graft (HLA-identical donor, 84% panel
      reactivity) was lost in a severe anti-B Ab-mediated acute rejection.
      Subsequently, the protocol included anti-CD20 for recipients of both A1 and B
      grafts and postoperative protocol IA to all recipients. The subsequent 10 grafts
      had excellent function, giving a total graft survival of 13/14 (observation range
      2 to 41 months). At 1 yr, mean serum creatinine was 113 micromol/l (n = 8) and
      mean glomerular filtration rate was 55 ml/min/1.73 m2 (range 24 to 77). In the
      remaining five cases, with less than 1 yr follow up, mean serum creatinine was
      145 micromol/l at 2 to 9 months follow up. Pre-IA anti-A/B titers were in the
      range of 2 to 32 (NaCl technique) and 16 to 512 (IAT). More than 90 IA sessions
      were performed in 14 recipients without any significant side effects. Recipient
      anti-A/B titers returned after transplantation to pre-IA levels or slightly
      lower. Postoperative renal biopsies were performed in 10 patients. In the 13
      patients with long-term function, one patient experienced cellular rejection
      (Banff IIB) at 3 months without anti-B titer rise. This rejection was concomitant
      with low tacrolimus plasma levels and was easily reversed by steroids. In 8 of 10
      cases, C4d staining was positive in peritubular capillaries. CONCLUSION: Blood
      group ABO-incompatible LD renal transplantation using A and B carbohydrate
      specific IA and anti-CD20 mAbs has excellent graft survival and function.

PMID- 16623811
TI  - Adult ABO-incompatible liver transplantation, using A and B donors.
AB  - BACKGROUND: The longer waiting time for a liver graft in patients with blood
      group O makes it necessary to expand the donor pool for these patients. This
      applies in both urgent situations and for elective patients. We report on our
      experience with ABO-incompatible liver transplantation using A2 and B non
      secretor donors here. PATIENTS AND METHODS: Between 1996 and 2005, 12 adult blood
      group O recipients (seven male/five female) received ABO-incompatible cadaveric
      liver grafts (10 A2 donors, two B non-secretor donors). The indications were
      either rapid deterioration of liver function or hepatocellular cancer, in blood
      group O recipients, where an ABO-identical/compatible graft was not available.
      Mean recipient age was 54+/-8 (mean+/-SD) yr. All pre-operative CDC crossmatches
      were negative. The initial immunosuppression was induction therapy with
      antithymocyte globulin (n = 3), interleukin 2 receptor antagonists (n = 3) or
      anti-CD20 antibody (rituximab) (n = 1), followed by a tacrolimus-based protocol.
      Three patients underwent plasmapheresis post-transplantation. Baseline biopsies
      were taken before or immediately after reperfusion of the graft and after
      grafting when clinically indicated. No pre-operative plasmapheresis,
      immunoadsorption or splenectomies were performed. RESULTS: Patient and graft
      survival was 10/12 (83%) and 8/12 (67%), respectively, with a 6.5-month median
      follow-up (range 10 days to 109 months). Two patients (B non-secretor grafts)
      died of multiorgan failure probably because of a poor condition before
      transplantation. Three patients were retransplanted. Causes of graft loss were
      bacterial arteritis (n = 1), death with a functioning graft (n = 1) and portal
      vein thrombosis (n = 2). In one of the patients with portal vein thrombosis, an
      anti-A titer increase occurred concomitantly, and ABO incompatibility as the
      cause of the thrombosis cannot be excluded. Seven acute rejections occurred in
      five patients and all were reversed by steroids or increased tacrolimus dosage.
      The pre-transplant anti-A titers tested against A1 red blood cells were 1 to 128
      (NaCl technique) and 4 to 1024 (indirect antiglobulin technique, IAT); the
      maximum postoperative titers were 16 to 2048 (NaCl) and 256 to 32,000 (IAT).
      CONCLUSION: The favorable outcome of A2 to O grafting, with a patient survival of
      10/10 and a graft survival of 8/10, makes it possible to also consider this blood
      group combination in non-urgent situations. The use of non-secretor donor grafts
      is interesting but has to be further documented. There was no hyperacute
      rejection or increased rate of rejection. Anti-A/B titer changes seem not to play
      a significant role in the monitoring of ABO-incompatible liver transplantation.

PMID- 16623812
TI  - Structural characterization of blood group A glycolipids in blood group A liver
      tissue in situ perfused with O blood: the dominating presence of type 1 core
      chain A antigens.
AB  - BACKGROUND: Biochemical studies of organ blood group antigen expression show a
      mixed pattern originating from both the organ tissue and remaining blood cells
      trapped in the organ despite in vitro perfusion of the vascular tree. The blood
      group A glycolipid expression was studied in a unique case in which a human liver
      had been in situ perfused by recipient blood. CASE HISTORY: A blood group O
      recipient was re-transplanted with an ABO incompatible A1Le (a - b +) liver.
      Because of discrepancy in size, liver segments II and III were removed 2 h after
      re-vascularization. Thereafter, the removed A1 liver segment was physiologically
      in situ perfused with O blood, eliminating a major part of the donor blood
      cells/plasma. EXPERIMENTAL: Total neutral glycolipids were isolated from the
      liver tissue and separated by high-performance liquid chromatography. Purified
      glycolipid fractions were stained with anti-A monoclonal antibodies (mAbs) and
      structurally characterized by mass spectrometry and proton nuclear magnetic
      resonance (NMR) spectroscopy. RESULTS: Two blood group A reactive glycolipid
      compounds were isolated. One component had a thin-layer chromatography (TLC)
      mobility as a six-sugar glycolipid and reacted with mAbs specific for A type 1
      mono-fucosyl structures. The second glycolipid fraction migrated as seven-sugar
      components and reacted with mAbs specific for type 1 difucosyl (ALeb) as well as
      Leb determinants. Mass spectrometry of the six-sugar component showed a structure
      similar to a blood group A hexaglycosylceramide with one fucose. Mass
      spectrometry and proton NMR spectroscopy of the seven-sugar fraction revealed a
      mixture of blood group Leb hexa- and ALeb hepta-glycosylceramides, respectively.
      All fractions were non-reactive with antibodies specific for A antigens based on
      types 3 and 4 core chain structures. In addition, TLC immunostaining of
      glycolipids isolated from blood group A livers, harvested for organ
      transplantation but discarded for various reasons, revealed trace amounts of
      several A glycolipids with a complex pattern. CONCLUSION: The in situ perfused
      liver tissue contains blood group A glycolipids based exclusively on type 1 core
      chains. The secretor gene (Se) codes for a fucosyltransferase acting on all core
      chain precursors while the H-gene fucosyltransferase only utilizes the type 2
      chain precursor. Whether this explains that only A type 1 chain compounds were
      found has to be established.

PMID- 16623813
TI  - ABO histo-blood group antigen expression on the graft endothelium long term after
      ABO-compatible, non-identical heart transplantation.
AB  - We recently reported a complete change in the endothelial ABO histo-blood group
      phenotype of a cardiac allograft long term after B to O mismatched
      transplantation. In the context of the current controversy on graft
      recolonization with recipient endothelial cells and its importance in the
      development of immunological unresponsiveness, we monitored the expression of
      endothelial ABH histo-blood group antigens of 10 ABO-compatible, non-identical
      cardiac allografts over an observation period of at least 30 months. ABH antigens
      as well as markers for endothelial cells, erythrocytes and thrombocytes were
      investigated retrospectively by immunohistochemistry using monoclonal antibodies
      on sections of formalin-fixed, paraffin-embedded biopsies and were evaluated semi
      quantitatively by microscopy. In contrast to our earlier finding of the change in
      the endothelial ABO histo-blood group phenotype long term after ABO- mismatched
      transplantation, we could not confirm this change in 10 compatible but non
      identical cases.

PMID- 16623814
TI  - Empiric versus preemptive therapy in the management of febrile neutropenia in the
      patient being treated for hematologic malignancy.

PMID- 16623815
TI  - Rejection rates in a randomised trial of tacrolimus monotherapy versus triple
      therapy in liver transplant recipients with hepatitis C virus cirrhosis.
AB  - BACKGROUND: Reducing immunosuppression not only reduces complications but also
      may lessen recurrent hepatitis C virus (HCV) infection after liver
      transplantation. PATIENTS/METHODS: HCV-infected cirrhotic patients randomised to
      tacrolimus monotherapy (MT) or triple therapy (TT) using tacrolimus 0.1
      mg/kg/day, azathioprine 1 mg/kg/day, and prednisolone 20 mg/day, tapering over 3
      months. RESULTS: Twenty-seven patients (MT) and 29 (TT)--median follow up 661
      days (range, 1-1603). Rejection episodes (protocol/further biopsies) within first
      3 months and use of empirical treatment were evaluated. New rejection was
      diagnosed if repeat biopsy (5-day interval) did not show improvement. Treated
      rejection episodes: 20 MT (15 biopsy-proven) vs. 24 TT (21 biopsy-proven), with
      19 (MT) vs. 24 (TT) methylprednisolone boluses. Overall: 35 episodes (MT) and 46
      (TT). Fewer MT patients had histological rejection (70%) than TT patients (86%),
      with fewer episodes of rejection (18.5% vs. 10%), and more moderate rejection
      (22% vs. 41%). The MT group had higher early tacrolimus levels. Rates of renal
      dysfunction, retransplantation, and death were not significantly different.
      CONCLUSION: Tacrolimus monotherapy is a viable immunosuppressive strategy in HCV
      infected liver transplant recipients.

PMID- 16623816
TI  - Non-comparative evaluation of the safety of aerosolized amphotericin B lipid
      complex in patients undergoing allogeneic hematopoietic stem cell
      transplantation.
AB  - Allogeneic hematopoietic stem cell transplant (HSCT) recipients are at increased
      risk for invasive fungal infections (IFIs) over prolonged periods of time.
      Aerosolized amphotericin B lipid complex (ABLC) has shown promise in lung
      transplant recipients as a convenient means of delivering protective drug to the
      upper airways avoiding systemic toxicities. The safety and tolerability of
      aerosolized ABLC in 40 subjects undergoing allogeneic HSCT was prospectively
      investigated in an open-labeled, non-comparative study. Subjects received
      aerosolized ABLC treatment once daily for 4 days, then once weekly for 13 weeks;
      fluconazole was administered daily as standard of care through post-transplant
      day 100. Pulmonary mechanics were measured before and after each dose of inhaled
      ABLC; adverse events (AEs) and the development of IFI were also monitored. Cough,
      nausea, taste disturbance, or vomiting followed 2.2% of 458 total inhaled ABLC
      administrations; 5.2% of inhaled ABLC administrations were associated with
      >or=20% decrease in pulmonary function measurements (forced expiratory volume in
      1 second or forced vital capacity) and none required treatment with
      bronchodilators or withdrawal from study. Four mild AEs were considered possibly
      or probably related to study treatment; no deaths or withdrawals from treatment
      were attributed to study drug. Of 3 proven IFIs occurring during the study
      period, only 1, a catheter-related case of disseminated fusariosis, occurred
      while the subject was receiving study medication. Aerosolized ABLC was well
      tolerated in allogeneic HSCT recipients. With only 1 of 40 subjects developing
      IFI while receiving treatment, the combination of fluconazole and inhaled ABLC
      warrants further study as antifungal prophylaxis following allogeneic HSCT.

PMID- 16623817
TI  - Cytomegalovirus infection of the liver transplant: virological, histological,
      immunological, and clinical observations.
AB  - The most common organ-specific manifestation of cytomegalovirus (CMV) infection
      after liver transplantation is hepatitis. Here we retrospectively describe the
      detailed virological, histological, immunological, and clinical findings
      associated with CMV infection in 229 consecutive adult liver transplantation
      patients. CMV infection was diagnosed by pp65 antigenemia. From 439 liver
      biopsies, CMV antigens were demonstrated by immunohistochemistry and CMV DNA by
      hybridization. The Banff criteria were used for histology. The expression of
      various adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular
      cell adhesion molecule-1 [VCAM-1], endothelial leukocyte adhesion molecule-1
      [ELAM-1]), their ligands (leukocyte function antigen-1 [LFA-1], very late antigen
      4 [VLA-4], Sialyl-LewisX-molecule [SLeX]), and lymphoid activation markers (major
      histocompatibility complex [MHC] Class II, interleukin-2-receptor [IL-2R]) was
      demonstrated by immunohistochemistry. CMV infection of the transplant occurred in
      26 patients (11% of all 229 patients and 17% of the 151 patients with liver
      biopsy). The incidence was higher among seronegative (26%) than in seropositive
      recipients (9%), but most cases 18/26 (70%) were reactivations. The CMV pp65
      antigenemia levels were usually high in primary infections (893+/-1069, range 50
      3000 pp65+cells), but varied widely in reactivations (388+/-740, range 3-3000).
      The histological Banff score was slightly increased (2.3+/-0.9). Microabscesses,
      lymphocytic infiltration, Kupffer cell reaction, and parenchymal alterations were
      common but viral inclusions rare. CMV significantly (P<0.05) increased ICAM-1 and
      VCAM-1 expression and the number of LFA-1, VLA-4, and Class II-positive
      lymphocytes in the graft. All CMV infections were successfully treated with
      antivirals. Intragraft CMV infection had no influence on the long-term outcome,
      but biliary complications were common. In conclusion, CMV infection of the liver
      transplant occurred both in primary infection and in reactivation, and also in
      the cases with low pp65 antigenemia levels. Microabscesses and other histological
      alterations were common but viral inclusions rare. Increased adhesion molecule
      expression was associated with lymphocyte infiltration. Successfully treated CMV
      hepatitis had no influence on the long-term clinical outcome.

PMID- 16623818
TI  - Impact of alternate definitions of fever resolution on the composite endpoint in
      clinical trials of empirical antifungal therapy for neutropenic patients with
      persistent fever: analysis of results from the Caspofungin Empirical Therapy
      Study.
AB  - BACKGROUND: Sensitivity analyses were incorporated in a Phase III study of
      caspofungin vs. liposomal amphotericin B as empirical antifungal therapy for
      febrile neutropenic patients to determine the impact of varying definitions of
      fever resolution on response rates. METHODS: The primary analysis used a 5-part
      composite endpoint: resolution of any baseline invasive fungal infection, no
      breakthrough invasive fungal infection, survival, no premature discontinuation of
      study drug, and fever resolution for 48 h during the period of neutropenia. Pre
      specified analyses used 3 other definitions for fever resolution: afebrile for 24
      h during the period of neutropenia, afebrile at 7 days post therapy, and
      eliminating fever resolution altogether from the composite endpoint. Patients
      were stratified on entry by use of antifungal prophylaxis and risk of infection.
      Allogeneic hematopoietic stem cell transplants or relapsed acute leukemia defined
      high-risk patients. RESULTS: In the primary analysis, 41% of patients in each
      treatment group met the fever-resolution criteria. Low-risk patients had shorter
      durations of neutropenia but failed fever-resolution criteria more often than
      high-risk patients. In each exploratory analysis, response rates increased in
      both treatment groups compared to the primary analysis, particularly in low-risk
      patients. CONCLUSIONS: Response rates for the primary composite endpoint for both
      treatment groups in this study were driven by low rates of fever resolution.
      Requiring fever resolution during neutropenia in a composite endpoint can mask
      more clinically relevant outcomes.

PMID- 16623819
TI  - Treatment of multidrug-resistant cytomegalovirus retinitis with systemically
      administered leflunomide.
AB  - Multiresistant cytomegalovirus (CMV) infection is increasingly recognized in
      solid organ transplant recipients. Leflunomide is a novel drug with both
      immunosuppressive and anti-CMV properties. Herein we report a case of a renal
      transplant recipient treated with leflunomide for multiresistant CMV retinitis,
      and provide correlation between serum and vitreous levels of leflunomide. She had
      stabilization of her retinitis and measurable levels of drug in her vitreous
      fluid and serum. These initial findings suggest that leflunomide may be useful in
      the treatment of CMV disease, including retinitis in patients after solid organ
      transplantation.

PMID- 16623820
TI  - Successful treatment with allogeneic peripheral blood stem cell transplantation
      and granulocyte transfusion for severe aplastic anemia with sinusitis.
AB  - A 43-year-old woman with severe aplastic anemia (SAA) received anti-thymocyte
      globulin and cyclosporin A (CyA) and achieved hematological remission. Although
      she had maintained hematological remission, the disease relapsed 10 months after
      arbitrary discontinuance of maintenance therapy with CyA. Resumption of CyA
      therapy was not effective, and her condition became complicated with progressive
      sinusitis with bone destruction, which was refractory to antibiotics, antifungal
      agents, granulocyte colony-stimulating factor, and surgical drainage. Because of
      the necessity for early neutrophil recovery (to resolve the infection), we
      proceeded with a combination therapy using allogeneic peripheral blood stem cell
      transplantation (PBSCT) promptly followed by granulocyte transfusion (GTX) from
      the same human leukocyte antigen-identical donor rather than carrying out a
      second immunosuppressive therapy. The patient showed temporal resolution of
      infection on the second day after a single GTX. Although the patient had
      pneumonia on day 11, it was resolved promptly after engraftment on day 16. This
      report suggests the clinical utility of a salvage therapy with allogeneic PBSCT
      followed by GTX in a particular case of recurrent SAA with refractory infections.

PMID- 16623822
TI  - Fatal adenovirus serotype-5 in a deceased-donor renal transplant recipient.

PMID- 16623821
TI  - IgG monitoring to identify the risk for development of infection in heart
      transplant recipients.
AB  - Infectious complication represents a significant source of morbidity and
      mortality in heart transplant recipients. To assess humoral immunity markers that
      can predict the development of infection, 38 consecutive recipients of heart
      transplants performed at a single center were prospectively studied. Induction
      therapy included daclizumab. Immunoglobulin (IgG, IgA, IgM) and complement
      factors (C3, C4, and factor B) were performed by nephelometry in peripheral blood
      samples obtained before transplantation, and 7 days and 1 month after
      transplantation. During a mean follow-up of 16.9 months, 13 patients had at least
      one episode of infection (34.2%). Eight of these were cytomegalovirus (CMV)
      infections treated with intravenous ganciclovir, 2 were bacterial pneumonia, 1
      patient had bacterial septicemia, 1 patient had urinary tract infection, and 1
      patient had pulmonary nocardiosis. No significant association was found between
      infection and age, sex, immunosuppression, CMV serostatus of donor and recipient,
      or treated rejection episodes. Pre-transplant IgG (below median value=1140 mg/dL;
      relative risk [RR] 3.69; 95% confidence interval [CI] 1.01-13.54; P=0.04) and
      post-transplant IgG levels at day 7 (below median value=679 mg/dL; RR 11.21; CI
      1.04-89.48; P=0.022) were associated with an increase in the risk for developing
      infections. Early monitoring of immunoglobulin levels might help to identify the
      risk for developing infection in heart transplantation.

PMID- 16623824
TI  - The essential haematopoietic transcription factor Scl is also critical for
      neuronal development.
AB  - Abstract The basic helix-loop-helix (bHLH) transcription factor Scl displays
      tissue-restricted expression and is critical for the establishment of the
      haematopoietic system; loss of Scl results in embryonic death due to absolute
      anaemia. Scl is also expressed in neurons of the mouse diencephalon,
      mesencephalon and metencephalon; however, its requirement in those sites remains
      to be determined. Here we report conditional deletion of Scl in neuronal
      precursor cells using the Cre/LoxP system. Neuronal-Scl deleted mice died
      prematurely, were growth retarded and exhibited an altered motor phenotype
      characterized by hyperactivity and circling. Moreover, ablation of Scl in the
      nervous system affected brain morphology with abnormal neuronal development in
      brain regions known to express Scl under normal circumstances; there was an
      almost complete absence of Scl-null neurons in the hindbrain and partial loss of
      Scl-null neurons in the thalamus and midbrain from early neurogenesis onwards.
      Our results demonstrate a crucial role for Scl in the development of Scl
      expressing neurons, including gamma-aminobutyric acid (GABA)ergic interneurons.
      Our study represents one of the first demonstrations of functional overlap of a
      single bHLH protein that regulates neural and haematopoietic cell development.
      This finding underlines Scl's critical function in cell fate determination of
      mesodermal as well as neuroectodermal tissues.

PMID- 16623825
TI  - Role of intracellular Ca2+ and calmodulin/MAP kinase kinase/extracellular signal
      regulated protein kinase signalling pathway in the mitogenic and antimitogenic
      effect of nitric oxide in glia- and neurone-derived cell lines.
AB  - To elucidate the mechanism of cell growth regulation by nitric oxide (NO) and the
      role played in it by Ca2+, we studied the relationship among intracellular Ca2+
      concentration ([Ca2+]i), mitogen-activated protein kinases [extracellular signal
      regulated protein kinase (ERK)] and proliferation in cell lines exposed to
      different levels of NO. Data showed that NO released by low [(z)-1-[2-aminiethyl]
      N-[2-ammonioethyl]amino]diazen-1-ium-1,2diolate (DETA/NO) concentrations (10
      microm) determined a gradual, moderate elevation in [Ca2+]i (46.8 +/- 7.2% over
      controls) which paralleled activation of ERK and potentiation of cell division.
      Functionally blocking Ca2+ or inhibiting calmodulin or MAP kinase kinase
      activities prevented ERK activation and antagonized the mitogenic effect of NO.
      Experimental conditions favouring Ca2+ entry into cells led to increased [Ca2+]i
      (189.5 +/- 4.8%), ERK activation and cell division. NO potentiated the Ca2+
      elevation (358 +/- 16.8%) and ERK activation leading to expression of p21Cip1 and
      inhibition of cell proliferation. Furthermore, functionally blocking Ca2+ down
      regulated ERK activation and reversed the antiproliferative effect of NO. Both
      the mitogenic and antimitogenic responses induced by NO were mimicked by a cGMP
      analogue whereas they were completely antagonized by selective cGMP inhibitors.
      These results demonstrate for the first time that regulation of cell
      proliferation by low NO levels is cGMP dependent and occurs via the
      Ca2+/calmodulin/MAP kinase kinase/ERK pathway. In this effect the amplitude of
      Ca2+ signalling determines the specificity of the proliferative response to NO
      possibly by modulating the strength of ERK activation. In contrast to the low
      level, the high levels (50-300 microm) of DETA/NO negatively regulated cell
      proliferation via a Ca2+-independent mechanism.

PMID- 16623826
TI  - Cystamine and cysteamine prevent 3-NP-induced mitochondrial depolarization of
      Huntington's disease knock-in striatal cells.
AB  - Abstract Cystamine significantly improved motor deficits and extended survival in
      mouse models of Huntington's disease (HD); however, the precise mechanism(s) by
      which cystamine and the related compound cysteamine are beneficial remain to be
      elucidated. Using clonal striatal cell lines from wild-type (STHdhQ7/HdhQ7) and
      mutant huntingtin knock-in (STHdhQ111/HdhQ111) mice, we have tested the
      hypothesis that cystamine and cysteamine could be beneficial by preventing the
      depolarization of mitochondria in cell cultures. Treatment with 3-nitroproprionic
      acid (3-NP), a mitochondrial complex II inhibitor, induces mitochondrial
      depolarization and cell death of mutant HD striatal cells but not of wild-type
      cells. The 3-NP-mediated decrease in the mitochondrial membrane potential was
      attenuated by 50 microm cystamine and completely inhibited by 250 microm
      cystamine. Similar results were obtained using cysteamine (50-500 microm). In
      addition, both cystamine and cysteamine significantly attenuated the 3-NP-induced
      cell death. Treatment of mutant HD striatal cells with 3-NP resulted in a robust
      decrease in the cellular and mitochondrial levels of glutathione (GSH) compared
      with cells exposed to the vehicle alone. Pre-treatment of the cells with
      cystamine and cysteamine completely prevented the 3-NP-mediated decrease in
      cellular and mitochondrial GSH levels. Incubation with L-buthionine (S,R)
      sulfoximine (BSO) 250 microm in combination with cystamine (250 microm) or
      cysteamine (250 microm) prior to being treated with 3-NP completely prevented the
      beneficial effects of cystamine and cysteamine on the 3-NP-mediated mitochondrial
      depolarization. These results demonstrate that cystamine and cysteamine prevent
      the 3-NP-induced mitochondrial depolarization of HD striatal cell cultures.

PMID- 16623827
TI  - NF-kappaB pathway: a target for preventing beta-amyloid (Abeta)-induced neuronal
      damage and Abeta42 production.
AB  - Beta-amyloid (Abeta) peptides are key proteins in the pathophysiology of
      Alzheimer's disease (AD). While Abeta42 aggregates very rapidly to form early
      diffuse plaques, supplemental Abeta40 deposition is required to form mature
      neuritic plaques. We here investigated the role of nuclear factor-kappaB (NF
      kappaB) pathway in Abeta40-mediated neuronal damage and amyloid pathology. In rat
      primary neurons and human postmitotic neuronal cells, the Abeta peptide induced a
      dose-dependent neuronal death, reduced the levels of the anti-apoptotic protein
      Bcl-XL, enhanced the cytosolic release of cytochrome c, and elicited the
      intracellular accumulation and secretion of Abeta42 oligomers. Moreover, Abeta40
      activated the NF-kappaB pathway by selectively inducing the nuclear translocation
      of p65 and p50 subunits, and promoted an apoptotic profile of gene expression. As
      inhibitors of the NF-kappaB pathway, we tested the capability of a double
      stranded kappaB decoy oligonucleotide, the anti-inflammatory drug aspirin and the
      selective IkappaB kinase 2 inhibitor, AS602868, to modify the Abeta40-mediated
      effects. These treatments, transiently applied before Abeta exposure, completely
      inhibited p50/p65 nuclear translocation and neuronal damage. The kappaB decoy
      also inhibited the Abeta-induced release of cytochrome c, restored the levels of
      Bcl-XL, and prevented intraneuronal accumulation and secretion of Abeta42. These
      results open up interesting perspectives on the development of novel strategies
      targeting out NF-kappaB p50/p65 dimers for pharmacological intervention in AD.

PMID- 16623828
TI  - Accumulation of the inhibitory receptor EphA4 may prevent regeneration of
      corticospinal tract axons following lesion.
AB  - Abstract We have examined the expression of Eph receptors and their ephrin
      ligands in adult rat spinal cord before and after lesion. Neurons in adult motor
      cortex express EphA4 mRNA, but the protein is undetectable in uninjured
      corticospinal tract. In contrast, after dorsal column hemisection EphA4 protein
      accumulates in proximal axon stumps. One of the ligands for EphA4, ephrinB2, is
      normally present in the grey matter flanking the corticospinal tract but after
      injury is markedly up-regulated in astrocytes in the glial scar. The result is
      that, after a lesion, corticospinal tract axons bear high levels of EphA4 and are
      surrounded to front and sides by a continuous basket of cognate inhibitory ephrin
      ligand. We suggest that a combination of EphA4 accumulation in the injured axons
      and up-regulation of ephrinB2 in the surrounding astrocytes leads to retraction
      of corticospinal axons and inhibition of their regeneration in the weeks after a
      spinal lesion.

PMID- 16623829
TI  - Cerebellar granule cell: ascending axon and parallel fiber.
AB  - Morphometric data have indicated that most (> 95%) of the granule cell axonal
      synapses are located along the parallel fibers. The ascending axons of granule
      cells, however, exert powerful excitatory effects on the activities of Purkinje
      cells. To resolve this apparent conflict, we propose that some of the parallel
      fiber synapses overlying a functionally homogeneous granule cell patch can
      discharge in close synchrony with the ascending axon synapses from that same
      granule cell patch, thereby augmenting the excitatory action from ascending
      axons. Moreover, we also propose that age may be an important factor in the
      ascending axon synapses. We examined the synaptic varicosities along the
      ascending axons and parallel fibers in the anterior lobe of the male NIA C57BL/6j
      mouse. Between 2.5 and 10 months, the fraction of synaptic varicosities
      anatomically associated with the ascending axons increased from 2.6% to 6.6%
      whereas the fraction of synaptic varicosities that can discharge in synchrony
      with ascending axon synapses (including some parallel fiber synapses) increased
      from 17.3% to 39% (assuming a granule cell patch of 300 x 300 microm). The
      results of the present study may be relevant to understanding the role of the
      ascending axon vs. the parallel fibers. Differential age-related synaptic changes
      in these two portions of the granule cell axons may constitute an important age
      dependent synaptic remodeling in the granule cell-Purkinje cell synaptic system.

PMID- 16623830
TI  - Sleep spindle-related activity in the human EEG and its relation to general
      cognitive and learning abilities.
AB  - Stage 2 sleep spindles have been previously viewed as useful markers for the
      development and integrity of the CNS and were more currently linked to 'offline
      re-processing' of implicit as well as explicit memory traces. Additionally, it
      had been discussed if spindles might be related to a more general learning or
      cognitive ability. In the present multicentre study we examined the relationship
      of automatically detected slow (< 13 Hz) and fast (> 13 Hz) stage 2 sleep
      spindles with: (i) the Raven's Advanced Progressive Matrices (testing 'general
      cognitive ability'); as well as (ii) the Wechsler Memory scale-revised
      (evaluating memory in various subdomains). Forty-eight healthy subjects slept
      three times (separated by 1 week) for a whole night in a sleep laboratory with
      complete polysomnographic montage. Whereas the first night only served adaptation
      and screening purposes, the two remaining nights were preceded either by an
      implicit mirror-tracing or an explicit word-pair association learning or
      (corresponding) control task. Robust relationships of slow and fast sleep
      spindles with both cognitive as well as memory abilities were found
      irrespectively of whether learning occurred before sleep. Based on the present
      findings we suggest that besides being involved in shaping neuronal networks
      after learning, sleep spindles do reflect important aspects of efficient cortical
      subcortical connectivity, and are thereby linked to cognitive- and memory-related
      abilities alike.

PMID- 16623831
TI  - Stress-induced sensitization of the limbic system in ovariectomized rats is
      partly restored by cyclic 17beta-estradiol administration.
AB  - Chronic stress induces neurobiological alterations which have consequences for
      subsequent stress handling. In the current experiment, ovariectomized rats were
      subjected daily to a stressor for 21 days. Thereafter, the rats were treated for
      21 days with 17beta-estradiol benzoate (10 microg/250 g, once every 4 days) or
      mirtazapine (10 mg/kg, daily). In this way, we were able to evaluate the ability
      of these compounds to reverse chronic stress-induced changes in the activity of
      the limbic system. After 21 days of recovery and treatment, the rats were re
      exposed to the adverse environment of the initial stressor and perfused 2 h
      later. Ovariectomized rats displayed increased numbers of c-Fos-positive nuclei,
      after re-exposure to the stressor, in the paraventricular nucleus of the
      hypothalamus, dentate gyrus, medial prefrontal cortex and central and medial
      amygdala. Cyclic estradiol treatment attenuated the sensitization of the
      paraventricular nucleus and central amygdala. Mirtazapine increased the number of
      c-Fos-positive nuclei in the central amygdala and dentate gyrus. Long-term
      transcriptional changes induced by chronic stress were determined with DeltaFosB
      immunoreactivity. The medial prefrontal cortex showed an increased number of
      DeltaFosB-positive nuclei after chronic stress and this was not affected by
      estradiol or mirtazapine administration during recovery. In conclusion, cyclic
      estradiol administration reversed chronic stress-induced sensitization in the
      limbic system, the paraventricular nucleus and central amygdala of female rats,
      output regions of the limbic system involved in fear responses. Mirtazapine did
      not achieve this reversal of stress-induced aberrations in the limbic system
      after 21 days of treatment.

PMID- 16623832
TI  - Delayed administration of deferoxamine reduces brain damage and promotes
      functional recovery after transient focal cerebral ischemia in the rat.
AB  - The mechanisms underlying functional recovery after stroke are poorly understood.
      Brain-adaptive responses to the hypoxic stress elicited by ischemia could
      contribute to these mechanisms. Indeed, hypoxia-inducible factor-1 (HIF-1), one
      of the main transcriptional factors regulated by oxygen level, increases the
      expression of several beneficial genes such as erythropoietin, glucose
      transporter-1 and vascular endothelial growth factor. In order to strengthen the
      expression of these hypoxia-inducible factors, we administered deferoxamine, an
      iron chelator known to stabilize HIF-1alpha protein expression, and examined its
      effects on the functional deficits induced by ischemia. Anesthetized Sprague
      Dawley rats were subjected to 60 min of intraluminal occlusion of the middle
      cerebral artery. Chronic deferoxamine treatment (300 mg/kg, s.c.), or its
      vehicle, started 24 h after ischemia and was continued bi-weekly until the
      animals were killed. Sensorimotor deficits were periodically assessed over 2
      months, and at this end point, the lesion volume was determined by histology.
      Treatment with deferoxamine significantly decreased the size of brain damage (
      28%) after ischemia and improved behavioral recovery. Indeed, neurological score
      and sensorimotor performances in the adhesive removal test recovered earlier in
      the deferoxamine-treated animals. Moreover, the long-lasting skilled forepaw
      reaching deficits were attenuated by deferoxamine. Although an antioxidant effect
      of deferoxamine cannot be excluded, the hypothesis that its beneficial effects
      could be mediated by an increase in HIF-1 target genes merits further
      investigations. Our data suggest that delayed administration of deferoxamine
      could represent an interesting therapeutical approach to treat focal cerebral
      ischemia.

PMID- 16623833
TI  - MPTP treatment of common marmosets impairs proteasomal enzyme activity and
      decreases expression of structural and regulatory elements of the 26S proteasome.
AB  - Dysfunction of the ubiquitin-proteasome system occurs in the substantia nigra
      (SN) in Parkinson's disease (PD). However, it is unknown whether this is a
      primary cause or a secondary consequence of other components of the pathogenic
      process. We have investigated in nonhuman primates whether initiating cell death
      through mitochondrial complex I inhibition using 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine hydrochloride (MPTP) altered proteasomal activity or the
      proteasomal components in the SN. Chymotrypsin-like, trypsin-like and
      peptidylglutamyl-peptide hydrolase (PGPH) activating of 20S proteasome were
      decreased in SN homogenates of MPTP-treated marmosets compared to naive animals.
      Western blotting revealed a marked decrease in the expression of 20S-alpha
      subunits, but no change in 20S-beta subunits in the SN of MPTP-treated marmoset
      compared to naive animals. There was a marked decrease in the expression of the
      proteasome activator 700 (PA700) and proteasome activator 28 (PA28) regulatory
      complexes. The 20S-alpha4 subunit immunoreactivity was decreased in the nucleus
      of colocalized tyrosine hydroxylase (TH)-positive cells of MPTP-treated animals
      compared to naive animals but no difference in the intensity of 20S-beta1i
      subunit staining. Immunoreactivity for PA700-Rpt5 and PA28-alpha subunits within
      surviving TH-positive cells of MPTP-treated marmoset was reduced compared to
      naive controls. Overall, the changes in proteasomal function and structure
      occurring follow MPTP-induced destruction of the SN in common marmosets were very
      similar to those found in PD. This suggests that altered proteasomal function in
      PD could be a consequence of other pathogenic processes occurring in SN as
      opposed to initiating cell death as previously suggested.

PMID- 16623834
TI  - IP3 receptor in the hair cells of frog semicircular canal and its possible
      functional role.
AB  - The presence and functional role of inositol trisphosphate receptors (IP3R) was
      investigated by electrophysiology and immunohistochemistry in hair cells from the
      frog semicircular canal. Intracellular recordings were performed from single
      fibres of the posterior canal in the isolated, intact frog labyrinth, at rest and
      during rotation, in the presence of IP3 receptor inhibitors and drugs known to
      produce Ca2+ release from the internal stores or to increase IP3 production. Hair
      cell immunolabelling for IP3 receptor was performed by standard procedures. The
      drug 2-aminoethoxydiphenyl borate (2APB), an IP3 receptor inhibitor, produced a
      marked decrease of mEPSP and spike frequency at low concentration (0.1 mm),
      without affecting mEPSP size or time course. At high concentration (1 mm), 2APB
      is reported to block the sarcoplasmic-endoplasmic reticulum Ca2+-ATPase (SERCA
      pump) and increase [Ca2+]i; at the labyrinthine cytoneural junction, it greatly
      enhanced the resting and mechanically evoked sensory discharge frequency. The
      selective agonist of group I metabotropic glutamate receptors (RS)-3,5
      dihydroxyphenylglycine (DHPG, 0.6 mm), produced a transient increase in resting
      mEPSP and spike frequency at the cytoneural junction, with no effects on mEPSP
      shape or amplitude. Pretreatment with cyclopiazonic acid (CPA, 0.1 mm), a SERCA
      pump inhibitor, prevented the facilitatory effect of both 2APB and DHPG,
      suggesting a link between Ca2+ release from intracellular stores and quantal
      emission. Consistently, diffuse immunoreactivity for IP3 receptors was observed
      in posterior canal hair cells. Our results indicate the presence and a possibly
      relevant functional role of IP3-sensitive stores in controlling [Ca2+]i and
      modulating the vestibular discharge.

PMID- 16623835
TI  - Metaplasticity of the late-phase of long-term potentiation: a critical role for
      protein kinase A in synaptic tagging.
AB  - The late-phase of long-term potentiation (L-LTP) in hippocampal area CA1 requires
      gene expression and de novo protein synthesis but it is expressed in an input
      specific manner. The 'synaptic tag' theory proposes that gene products can only
      be captured and utilized at synapses that have been 'tagged' by previous
      activity. The mechanisms underlying synaptic tagging, and its activity
      dependence, are largely undefined. Previously, we reported that low-frequency
      stimulation (LFS) decreases the stability of L-LTP in a cell-wide manner by
      impairing synaptic tagging. We show here that a phosphatase inhibitor, okadaic
      acid, blocked homosynaptic and heterosynaptic inhibition of L-LTP by prior LFS.
      In addition, prior LFS homosynaptically and heterosynaptically impaired
      chemically induced synaptic facilitation elicited by forskolin/3-isobutyl-1
      methylxanthine, suggesting that there is a cell-wide dampening of cAMP/protein
      kinase A (PKA) signaling concurrent with phosphatase activation. We propose that
      prior LFS impairs expression of L-LTP by inhibiting synaptic tagging through its
      actions on the cAMP/PKA pathway. In support of this notion, we show that
      hippocampal slices from transgenic mice that have genetically reduced hippocampal
      PKA activity display impaired synaptic capture of L-LTP. An inhibitor of PKA, KT
      5720, also blocked synaptic capture of L-LTP. Moreover, pharmacological
      activation of the cAMP/PKA pathway can produce a synaptic tag to capture L-LTP
      expression, resulting in persistent synaptic facilitation. Collectively, our
      results show that PKA is critical for synaptic tagging and for input-specific L
      LTP. PKA-mediated signaling can be constrained by prior episodes of synaptic
      activity to regulate subsequent L-LTP expression and perhaps control the
      integration of multiple synaptic events over time.

PMID- 16623836
TI  - Electrophysiology in ischemic neocortical brain slices: species differences vs.
      influences of anaesthesia and preparation.
AB  - Ischemia models are indispensable for the evaluation of measures to be clinically
      applied to brain trauma or stroke patients. Slice models provide good control
      over experimental parameters and allow for comparative examinations of human and
      animal brain tissue. Experimental tissue, however, may be altered by anaesthesia,
      preparatory technique, and, in the case of human tissue, by underlying diseases.
      These influences on tissue behaviour under ischemia were examined
      electrophysiologically. Native rat tissue slices were prepared either immediately
      after decapitation (n = 13), during short ether/barbiturate narcosis (n = 18), or
      after two hours of inhalation anaesthesia (n = 12) imitating clinical narcosis.
      Tissue from rats in which generalized amygdala-kindled seizures had been
      triggered by electric stimulation (n = 10) was prepared according to the
      decapitation protocol, while human tissue (n = 10) was obtained during epilepsy
      or tumour surgery. Electrophysiological data (latency and amplitude of anoxic
      depolarization, recovery of evoked potentials) were recorded during ischemia
      simulation. Neither details of preparation or anaesthesia nor a history of
      epileptic fits were associated with significant changes of electrophysiological
      reactions under ischemia. Human tissue showed a significantly higher ability to
      uphold transmembrane ion gradients under ischemia. The ability of brain tissue to
      withstand ischemia is obviously species dependent. For the transfer of
      experimental results into clinical use it is important that interspecies
      differences alone can bring about a significant change of tissue behaviour.

PMID- 16623837
TI  - Learning-induced oscillatory activities correlated to odour recognition: a
      network activity.
AB  - In trained behaving rats, the expression of a prominent beta oscillatory activity
      in the olfactory system was previously identified as a correlate of odour
      recognition. The aim of the present study was to assess the putative role of a
      functional coupling between the olfactory bulb (OB) and higher structures in this
      activity. We performed a unilateral inactivation of the medial part of the
      olfactory peduncle by lidocaine infusion. Inactivation deprived the OB from most
      of its centrifugal afferences, including feedback connections from the piriform
      cortex (PC) while sparing the ascending fibres from the OB to higher cortical
      structures. This treatment reduced the amplitude of odour-induced oscillatory
      beta responses both in OB and PC. In parallel, gamma activity classically
      observed in these two structures during spontaneous activity displayed a strong
      enhancement. Results suggest that odour-induced oscillatory response could be the
      emergent feature of an olfactory functional network set up through learning.

PMID- 16623838
TI  - Firing cell repertoire during carbachol-induced theta rhythm in rat hippocampal
      formation slices.
AB  - One hundred and seven cells were recorded extracellularly in hippocampal
      formation (HPC) slices during carbachol-induced theta. The data obtained provided
      evidence of a population of HPC neurons which, when activated cholinergically,
      participate in the generation of in vitro theta. The activity patterns of in
      vitro recorded theta-related cells were shown to be similar to those of theta
      related cells recorded in vivo and cells recorded in vitro during cholinergically
      induced theta, and non-theta intervals were successfully classified according to
      previously developed criteria for in vivo recorded theta-related cells. The
      current in vitro experiments showed that, in addition to theta-on and theta-off
      cells, the HPC contained cells that were probably involved in programming the
      appearance and duration of theta epochs and the intervals between theta epochs.
      These novel types of cells were termed 'gating cells'.

PMID- 16623839
TI  - Nicotine exposure in vivo induces long-lasting enhancement of NMDA receptor
      mediated currents in the hippocampus.
AB  - The use of nicotine via cigarette smoking forms long-lasting memories that are
      recalled in response to environmental cues associated with previous nicotine use.
      However, the changes in brain memory systems that underlie these long-lasting
      memories are not well understood. The N-methyl-D-aspartate receptor (NMDAR) is
      critical for long-lasting modifications of synapses. Here we show that in vivo
      nicotine exposure induces the enhancement of NR2B-containing NMDAR-mediated
      currents in the hippocampus, a brain region associated with the formation of
      memories. This nicotine effect is maintained during continued nicotine exposure
      and is accompanied by increased tyrosine phosphorylation of NR2B. Furthermore,
      long-term potentiation (LTP), which is considered to be a cellular substrate of
      learning and memory, induced in nicotine-exposed hippocampi contains a protein
      synthesis-independent long-lasting component. An NR2B-selective antagonist blocks
      a long-lasting component of LTP, but not LTP. These results suggest that exposure
      to nicotine provides conditions that promote the induction of long-lasting
      modifications of synapses, which may be involved in the formation of memories
      involving nicotine use.

PMID- 16623840
TI  - Neurogenesis in the R6/1 transgenic mouse model of Huntington's disease: effects
      of environmental enrichment.
AB  - Previous work has demonstrated that the transgenic R6/1 mouse model of
      Huntington's disease has decreased proliferation of neural precursor cells (NPCs)
      in the dentate gyrus of the hippocampus. This study therefore examined the
      survival and differentiation of NPCs in presymptomatic and symptomatic R6/1 mice
      and the effects of environmental enrichment on these variables. Here it is
      demonstrated that the survival of bromodeoxyuridine-positive (BrdU+) NPCs in the
      dentate gyrus is decreased in the transgenic mice. In addition, the number of
      doublecortin-positive (DCX+) cells is greatly reduced in these mice, as is the
      total number of new mature neurons, while the proportion of BrdU+ cells
      differentiating into mature neurons was not significantly different between
      genotypes. Furthermore, the DCX+ cells in the R6/1 mice had smaller and irregular
      shaped somas, shorter neurites, and migrated a shorter distance into the granular
      cell layer compared with wild-type mice. Older symptomatic mice housed in an
      enriched environment had an increased number of BrdU+ and DCX+ cells as well as
      longer neurites and increased migration of DCX+ cells. There was no significant
      difference between genotypes or environments in the number of BrdU+ cells in the
      subventricular zone. These results suggest that decreased neurogenesis might be
      responsible, in part, for the hippocampal deficits observed in these mice and
      that environmental enrichment produces morphological changes in newborn granule
      neurons in both wild-type and R6/1 mice, which could underlie some of the
      beneficial effects of enrichment.

PMID- 16623841
TI  - Enhanced perisomatic inhibition and impaired long-term potentiation in the CA1
      region of juvenile CHL1-deficient mice.
AB  - The cell adhesion molecule, CHL1, like its close homologue L1, is important for
      normal brain development and function. In this study, we analysed the functional
      role of CHL1 in synaptic transmission in the CA1 region of the hippocampus using
      juvenile CHL1-deficient (CHL1-/-) and wild-type (CHL1+/+) mice. Inhibitory
      postsynaptic currents evoked in pyramidal cells by minimal stimulation of
      perisomatically projecting interneurons were increased in CHL1-/- mice compared
      with wild-type littermates. Also, long-term potentiation (LTP) at CA3-CA1
      excitatory synapses was reduced under physiological conditions in CHL1-/- mice.
      This abnormality was abolished by application of a GABAA receptor antagonist,
      suggesting that enhanced inhibition is the cause of LTP impairment. Quantitative
      ultrastructural and immunohistochemical analyses revealed aberrations possibly
      related to the abnormally high inhibition observed in CHL1-/- mice. The length
      and linear density of active zones in symmetric synapses on pyramidal cell
      bodies, as well as number of perisomatic puncta containing inhibitory axonal
      markers were increased. Density and total number of parvalbumin-positive
      interneurons was also abnormally high. These observations and the finding that
      CA1 interneurons express CHL1 protein indicate that CHL1 is important for
      regulation of inhibitory synaptic transmission and interneuron populations in the
      postnatal brain. The observed enhancement of inhibitory transmission in CHL1-/-
      mice is in contrast to the previous finding of reduced inhibition in L1 deficient
      mice and indicates different functions of these two closely related molecules.

PMID- 16623842
TI  - Long-term stability of fear memory depends on the synthesis of protein but not
      mRNA in the amygdala.
AB  - Synaptic modification supporting memory formation is thought to depend on gene
      expression and protein synthesis. Disrupting either process around the time of
      learning prevents the formation of long-term memory. Recent evidence suggests
      that memory also becomes susceptible to disruption upon retrieval. Whether or not
      the molecular events involved in the formation of new memory are the same as what
      is needed for memory to persist after retrieval has yet to be determined. In the
      present set of experiments, rats were given inhibitors of protein or messenger
      ribonucleic acid (mRNA) synthesis into the amygdala just after training or
      retrieval of fear memory. Results showed that blocking mRNA or protein synthesis
      immediately after learning prevented the formation of long-term memory, while
      stability of memory after retrieval required protein, but not mRNA, synthesis.
      These data suggest that the protein needed for memory reconsolidation after
      retrieval may be transcribed from pre-existing stores of mRNA.

PMID- 16623843
TI  - Estrogen receptor-beta gene disruption potentiates estrogen-inducible aggression
      but not sexual behaviour in male mice.
AB  - Aggressive behaviour of gonadally intact male mice is increased by estrogen
      receptor (ER)-beta gene disruption, whereas sexual behaviour remains unchanged.
      The elevated aggression levels following ER-beta gene disruption is pronounced
      during repeated aggression tests in young animals and the first aggression test
      in adults. In the present study, the roles of ER-beta activation in the
      regulation of aggressive and sexual behaviour were investigated in gonadectomized
      ER-beta knockout (betaERKO) and wild-type (WT) male mice treated with various
      doses of estrogen. Overall, estradiol benzoate (EB) treatment induced higher
      levels of aggression in betaERKO mice than in WT mice. In WT mice, the levels of
      aggression induced by EB were highest in the lowest-dose (2.5 microg/day) group
      and gradually decreased in higher-dosage groups. On the other hand, equally high
      levels of aggressive behaviour were induced by all three doses of EB in betaERKO
      mice. A marked genotype difference in dose responses is inferred, such that the
      ER-alpha-mediated facilitatory action of estrogen is more pronounced at lower and
      physiological doses and the ER-beta-mediated inhibitory action is only unveiled
      at higher doses of estrogen. In contrast to aggression, the levels of sexual
      behaviour induced by EB were not different between betaERKO and WT at either dose
      of EB (2.5 and 12.5 microg/day) examined. These findings support the notion that
      ER-beta activation may exert an attenuating action on male aggression induced by
      estrogen through ER-alpha-mediated brain mechanisms, whereas its effect on male
      sexual behaviour is relatively small.

PMID- 16623844
TI  - Neuroanatomical specificity in the expression of the immediate early gene c-fos
      following expression of appetitive and consummatory male sexual behaviour in
      Japanese quail.
AB  - We investigated the neural sites related to the occurrence of appetitive (ASB)
      and consummatory (CSB) aspects of male sexual behaviour in Japanese quail.
      Castrated males treated with testosterone were exposed for 5 min to one of four
      experimental conditions: (i) free interaction with a female (CSB group); (ii)
      expression of rhythmic cloacal sphincter movements in response to the visual
      presentation of a female (ASB-F group); (iii) or a male (ASB-M group), and (iv)
      handling as a control manipulation. Brains were collected 90 min after the start
      of behavioural tests and stained by immunocytochemistry for the FOS protein. An
      increase in FOS expression was observed throughout the rostro-caudal extent of
      the medial preoptic nucleus (POM) in CSB males, whereas the view of a female (ASB
      F) induced an increased FOS expression in the rostral POM only. In the CSB group,
      there was also an increase in FOS expression in the bed nucleus striae
      terminalis, and both the CSB and ASB-F groups exhibited increased FOS expression
      in aspects of the ventro-lateral thalamus (VLT) related to visual processing.
      Moreover, both the CSB and ASB-M groups showed increased FOS expression in the
      lateral septum. These data provide additional support to the idea that there is a
      partial anatomical dissociation between structures involved in the control of
      both aspects of male sexual behaviour and independently provide data consistent
      with a previous lesion study that indicated that the rostral and caudal POM
      differentially control the expression of ASB and CSB in quail.

PMID- 16623845
TI  - The role of the medial caudate nucleus, but not the hippocampus, in a matching-to
      sample task for a motor response.
AB  - A delayed-match-to-sample task was used to assess memory for motor responses in
      rats with control, hippocampus, or medial caudate nucleus (MCN) lesions. All
      testing was conducted on a cheeseboard maze in complete darkness using an
      infrared camera. A start box was positioned in the centre of the maze facing a
      randomly determined direction on each trial. On the sample phase, a
      phosphorescent object was randomly positioned to cover a baited food well in one
      of five equally spaced positions around the circumference of the maze forming a
      180-degree arc 60 cm from the box. The rat had to displace the object to receive
      food and return to the start box. The box was then rotated to face a different
      direction. An identical baited phosphorescent object was placed in the same
      position relative to the start box. A second identical object was positioned to
      cover a different unbaited well. On the choice phase, the rat must remember the
      motor response made on the sample phase and make the same motor response on the
      choice phase to receive a reward. Hippocampus lesioned and control rats improved
      as a function of increased angle separation used to separate the correct object
      from the foil (45, 90, 135, and 180 degrees) and matched the performance of
      controls. However, rats with MCN lesions were impaired across all separations.
      Results suggest that the MCN, but not the hippocampus, supports working memory
      and/or a process aimed at reducing interference for motor response selection
      based on vector angle information.

PMID- 16623846
TI  - Rule-dependent shifting of sensorimotor representation in the primate prefrontal
      cortex.
AB  - When we react to the outer world, perceived sensory information is frequently
      memorized over a temporal interval then transformed into a motor command based on
      a behavioural rule. In this type of memory-based sensorimotor transformation,
      working memory is considered to play an important role. It has been suggested
      that the lateral prefrontal cortex is involved in the process of the working
      memory. However, the neuronal mechanism for guiding a motor command from the
      working memory has not been established. To examine how visuospatial working
      memory is linked with a forthcoming saccade direction, we used an antisaccade
      paradigm for monkeys in which a behavioural rule was presented in the middle of a
      delay period. In this task, the subjects were required to maintain cue location
      and to select a response based on a behavioural rule. We found that a subset of
      mnemonic neurons in the lateral prefrontal cortex changed their representation
      from cue to saccade direction. Furthermore, the discriminability for saccade
      direction of these neurons tended to appear soon after the behavioural rule
      presentation, indicating their significant dependency on the behavioural rule.
      These results suggest that a subset of mnemonic neurons in the lateral prefrontal
      cortex change their activity depending on a behavioural rule to guide a
      prospective motor command.

PMID- 16623847
TI  - Tight covariation of BOLD signal changes and slow ERPs in the parietal cortex in
      a parametric spatial imagery task with haptic acquisition.
AB  - The present study investigated the relation of brain activity patterns measured
      with functional magnetic resonance imaging (fMRI) and slow event-related
      potentials (ERPs) associated with a complex cognitive task. A second goal was to
      examine the neural correlates of spatial imagery of haptically--instead of
      visually--acquired representations. Using a mental image scanning task, spatial
      imagery requirements were systematically manipulated by parametrically varying
      the distance between haptically acquired landmarks. Results showed a close
      relation between slow ERPs and the blood oxygenation level dependent (BOLD)
      signal in human parietal lobe. Reaction times of mental scanning correlated with
      the distances between landmarks on the learned display. In parallel, duration and
      amplitude of slow ERPs and duration of the haemodynamic response systematically
      varied as a function of mental scanning distance. Source analysis confirmed that
      the ERP imagery effect likely originated from the same cortical substrate as the
      corresponding BOLD effect. This covariation of the BOLD signal with slow ERPs is
      in line with recent findings in animals demonstrating a tight link between local
      field potentials and the BOLD signal. The parietal location of the imagery effect
      is consistent with the idea that externally triggered (perceptual) and mentally
      driven (imagery) spatial processes are both mediated by the same supramodal brain
      areas.

PMID- 16623848
TI  - Prediction of the main cortical areas and connections involved in the tactile
      function of the visual cortex by network analysis.
AB  - We explored the cortical pathways from the primary somatosensory cortex to the
      primary visual cortex (V1) by analysing connectional data in the macaque monkey
      using graph-theoretical tools. Cluster analysis revealed the close relationship
      of the dorsal visual stream and the sensorimotor cortex. It was shown that
      prefrontal area 46 and parietal areas VIP and 7a occupy a central position
      between the different clusters in the visuo-tactile network. Among these
      structures all the shortest paths from primary somatosensory cortex (3a, 1 and 2)
      to V1 pass through VIP and then reach V1 via MT, V3 and PO. Comparison of the
      input and output fields suggested a larger specificity for the 3a/1-VIP-MT/V3-V1
      pathways among the alternative routes. A reinforcement learning algorithm was
      used to evaluate the importance of the aforementioned pathways. The results
      suggest a higher role for V3 in relaying more direct sensorimotor information to
      V1. Analysing cliques, which identify areas with the strongest coupling in the
      network, supported the role of VIP, MT and V3 in visuo-tactile integration. These
      findings indicate that areas 3a, 1, VIP, MT and V3 play a major role in shaping
      the tactile information reaching V1 in both sighted and blind subjects. Our
      observations greatly support the findings of the experimental studies and provide
      a deeper insight into the network architecture underlying visuo-tactile
      integration in the primate cerebral cortex.

PMID- 16623849
TI  - Short- and long-term modulation of upper limb motor-evoked potentials induced by
      acupuncture.
AB  - The aim of this study was to investigate in humans the effects of acupuncture
      upon upper-limb motor-evoked potentials (MEPs), elicited by transcranial magnetic
      stimulation of the primary motor cortex. It is known that peripheral sensory
      stimulation can be used to induce short- and long-term changes in motor cortex
      excitability. Data show that the simple insertion of the needle is an adequate
      somatosensory stimulus to induce a significant modulation of MEP amplitude, the
      sign of which (facilitation or inhibition) is specific to the investigated muscle
      and to the point of needle insertion. Moreover, MEP changes in upper-limb muscles
      are also observed following needling of lower-limb sites, revealing the presence
      of long-distance effects of acupuncture. Finally, the modulation in muscle
      excitability considerably outlasts the time period of needle application,
      demonstrating the induction of long-term plastic changes in the central nervous
      system. In addition, results have shown that the effects on muscle excitability
      are not restricted to the stimulation of well-coded acupoints, as described in
      traditional Chinese medicine, but they can also be induced by needling of
      nonacupoints, normally not used for therapeutic purposes. The possible neuronal
      mechanisms underlying the observed effects of acupuncture are discussed in
      relation to the available neurophysiological data regarding the interlimb
      reflexes and the changes in the representational cortical maps induced in humans
      by a prolonged somatosensory stimulation.

PMID- 16623850
TI  - Nitric oxide-dependent long-term potentiation revealed by real-time imaging of
      nitric oxide production and neuronal excitation in the dorsal horn of rat spinal
      cord slices.
AB  - Nitric oxide (NO) is thought to be involved in the central mechanism of
      hyperalgesia and allodynia at the spinal level. Recently, we reported that NO
      played an important role in the induction of long-term potentiation (LTP) of
      synaptic strength in spinal dorsal horn, which is believed to underlie
      hyperalgesia and allodynia. In this study, to elucidate the relationship of NO to
      LTP in spinal dorsal horn, we measured the spatiotemporal distribution of NO
      signal with the NO-sensitive dye, DAR-4M, and neuronal excitation with the
      voltage-sensitive dye, RH482, in rat spinal cord slices, elicited by dorsal root
      stimulation. In superficial dorsal horn, neuronal excitation evoked by C fiber
      activating dorsal root stimulation was potentiated for more than 2 h after low
      frequency conditioning stimulation (LFS, 240 pulses at 2 Hz for 2 min). In the
      same slices that exhibited LTP, NO was produced and distributed in the
      superficial dorsal horn during the delivery of LFS, and the amplitude of LTP and
      amount of NO production showed close correlation from slice to slice. LTP and
      production of NO were inhibited in the presence of the NO synthase inhibitors and
      an inhibitor of heme oxygenase, the synthetic enzyme for carbon monoxide (CO).
      These results suggest that production and distribution of NO is necessary for the
      induction of LTP in spinal dorsal horn, and that CO contributes to the LTP
      induction and NO production by LFS.

PMID- 16623851
TI  - Variations in the human cannabinoid receptor (CNR1) gene modulate striatal
      responses to happy faces.
AB  - Happy facial expressions are innate social rewards and evoke a response in the
      striatum, a region known for its role in reward processing in rats, primates and
      humans. The cannabinoid receptor 1 (CNR1) is the best-characterized molecule of
      the endocannabinoid system, involved in processing rewards. We hypothesized that
      genetic variation in human CNR1 gene would predict differences in the striatal
      response to happy faces. In a 3T functional magnetic resonance imaging (fMRI)
      scanning study on 19 Caucasian volunteers, we report that four single nucleotide
      polymorphisms (SNPs) in the CNR1 locus modulate differential striatal response to
      happy but not to disgust faces. This suggests a role for the variations of the
      CNR1 gene in underlying social reward responsivity. Future studies should aim to
      replicate this finding with a balanced design in a larger sample, but these
      preliminary results suggest neural responsivity to emotional and socially
      rewarding stimuli varies as a function of CNR1 genotype. This has implications
      for medical conditions involving hypo-responsivity to emotional and social
      stimuli, such as autism.

PMID- 16623852
TI  - Transfer of interfered motor patterns to self from others.
AB  - Previous behavioural and neuroimaging data on humans demonstrated that kinematics
      and the level of brain activity vary according to whether participants reach
      towards and grasp a target object presented in isolation or flanked by a
      distractor object. Here we seek to explore whether a differential activation can
      be revealed by the mere observation of another person grasping an object in
      isolation or alongside a distractor. To this end we used event-related functional
      magnetic resonance imaging to localize neural activity related to action
      observation that was influenced by the presence of a distractor object. We found
      that observing a human model reaching-to-grasp a three-dimensional target
      alongside a distractor elicits a differential level of activation in a network of
      areas typically involved during action observation: the dorsal sectors of the
      premotor cortex and the inferior frontal gyrus. Whereas our previous
      understanding of the human action observation system has been restricted to
      actions directed to single objects, we provide compelling evidence that areas
      within this network modulate with respect to the context in which the observed
      action takes place. This may prove to be a fundamental process for our
      understanding of how others' actions can be represented at a neural level.

PMID- 16623853
TI  - Reduction in subthalamic 8-35 Hz oscillatory activity correlates with clinical
      improvement in Parkinson's disease.
AB  - Strong synchronization of neuronal activity occurs in the 8-35 Hz band in the
      subthalamic nucleus (STN) of patients with Parkinson's disease (PD) and is
      evident as oscillatory local field potential (LFP) activity. To test whether such
      synchronization may contribute to bradykinesia and rigidity, we sought
      correlations between the suppression of synchronization at 8-35 Hz in STN and the
      reduction in Parkinsonism with levodopa. LFPs were recorded on and off medication
      from STN deep-brain stimulation electrodes in nine PD patients. LFP power was
      calculated over the frequencies of the most prominent spectral peak within the 8
      35 Hz frequency band on each of 17 sides (off medication), and over the
      frequencies of any peak in the 60-90 Hz band, if present (seven sides, on
      medication). Levodopa-induced reduction of LFP power over these two frequency
      ranges was then correlated with improvement in motor impairment as assessed by
      the Unified Parkinson's Disease Rating Scale (UPDRS). The reduction in peak
      activity in the 8-35 Hz band with levodopa positively correlated with the
      improvement in the contralateral hemibody motor UPDRS score with levodopa (r =
      0.811, P < 0.001) as well as with hemibody subscores of akinesia-rigidity (r =
      0.835, P < 0.001), but not tremor. A trend for negative correlations was found
      between peak 60-90 Hz LFP power and UPDRS hemibody score, suggesting that
      positive correlations were relatively frequency-specific. Our results support a
      link between levodopa-induced improvements in bradykinesia and rigidity and
      reductions in population synchrony at frequencies < 35 Hz in the region of the
      STN in patients with PD.

PMID- 16623854
TI  - Immune function tests for hazard identification: a paradigm shift in drug
      development.
AB  - Routine immune function testing in preclinical drug development was established
      as a regulatory requirement in June of 2000 under the Committee of Proprietary
      Medicinal Products (CPMP) Note for Guidance on Repeated Dose Toxicity
      (CPMP/SWP/1042/99). The purpose of the more stringent approach to
      immunotoxicology testing was to better identify unintended immunosuppression;
      however, the requirement was met with much discussion and debate. At the center
      of the discussion was an attempt to reconcile opposing regulatory directives from
      agencies outside of Europe that adhere to a more selective, weight-of-evidence
      approach to functional evaluations. Uncertainty over the predictive value of the
      recommended immune function tests relative to conventional toxicology parameters
      prompted an investigation by the International Committee on Harmonization (ICH).
      The results of a preliminary, industry-wide survey indicated that only a low
      percentage of pharmaceuticals adversely affect immune function without
      alterations to standard toxicology parameters. Expected ICH guidelines will
      ultimately determine to what extent and for what purpose immune function tests
      will be conducted. In the meantime, optimization of the recommended immune
      function tests is ongoing. The T-cell dependent antibody response (TDAR) by
      either conventional Sheep Red Blood Cell (SRBC) plaque assay or by the modified
      ELISA method using either SRBC or keyhole limpet hemocyanin (KLH) as antigen is
      being extensively evaluated to determine best practices and procedures for
      preclinical immunotoxicity evaluations. This review addresses some aspects of the
      debate concerning the appropriateness of immune function tests for hazard
      identification, along with recommendations for optimizing TDAR methodology to
      ensure adequate sensitivity and predictability in risk assessments for
      immunotoxicity.

PMID- 16623855
TI  - The alkaline comet assay: towards validation in biomonitoring of DNA damaging
      exposures.
AB  - Generation of DNA damage is considered to be an important initial event in
      carcinogenesis. The single cell gel electrophoresis (comet) assay is a
      technically simple and fast method that detects genotoxicity in virtually any
      mammalian cell type without requirement for cell culture. This review discusses
      the strength of the comet assay in biomonitoring at its present state of
      validation. The simple version of the alkaline comet assay detects DNA migration
      caused by strand breaks, alkaline labile sites, and transient repair sites. By
      incubation with bacterial glycosylase/endonuclease enzymes, broad classes of
      oxidative DNA damage, alkylations, and ultraviolet light-induced photoproducts
      are detected as additional DNA migration. The most widely measured enzyme
      sensitive sites have been those detected by formamidopyrimidine DNA glycosylase
      (FPG) and endonuclease III (ENDOIII). Reports from biomonitoring studies show
      that the basal level of DNA damage in leukocytes is influenced be a variety of
      lifestyle and environmental exposures, including exercise, air pollution,
      sunlight, and diet. Although not all types of carcinogenic exposures should be
      expected to damage DNA in leukocytes, the comet assay is a valuable method for
      detection of genotoxic exposure in humans. However, the predictive value of the
      comet assay is unknown because it has not been investigated in prospective cohort
      studies. Also, it is important that the performance of the assay is investigated
      in multi-laboratory validation trials. As a tool in risk assessment the comet
      assay can be used in characterization of hazards.

PMID- 16623856
TI  - Rewarding properties of 1-benzylpiperazine, a new drug of abuse, in rats.
AB  - 1-Benzylpiperazine (also known as 'Legal X', 'Legal E', or 'A2') is a
      psychoactive compound increasingly encountered on the clandestine market.
      Previous experimental data suggest that the compound possesses addictive
      properties. In the present study, we used the conditioned place preference method
      in the rat to test whether 1-benzylpiperazine possesses rewarding properties.
      Furthermore, the mechanisms of the 1-benzylpiperazine reward were investigated
      using selected dopamine and serotonin receptor antagonists. 1-Benzylpiperazine
      (1.25, 5, and 20 mg/kg) induced dose-dependently place preference. This place
      preference was attenuated by the antagonists SCH23390 (0.2 mg/kg; dopamine D1
      like receptors) and MDL72222 (1.0 mg/kg; serotonin3 receptors), but not by
      raclopride (0.8 mg/kg; dopamine D2-like receptors) or ketanserin (2 mg/kg;
      preferentially serotonin2 receptors). Our results show that 1-benzylpiperazine
      possesses rewarding properties in the rat, which suggests the compound to be
      susceptible to human abuse. The brain dopaminergic and serotonergic systems
      appear to be involved in the 1-benzylpiperazine reward.

PMID- 16623857
TI  - Treatment of experimental chronic chagas disease with trifluralin.
AB  - We tested trifluralin against Trypanosoma cruzi in a model of chronic Chagas
      disease in mice. CF1 mice (n=148) were intraperitoneally infected with 10(5)
      trypomastigotes of T. cruzi, H510C8C3 clone. One hundred mice were partially
      treated with benznidazole. Mortality was 100% at day 41 in the control group
      (n=48). At day 90 of the chronic disease (74% survival) mice were divided into
      three groups and treated orally with trifluralin (50 mg/kg/day, n=26),
      benznidazole (50 mg/kg/day, n=25) and vehicle (peanut oil; control group, n=23)
      for 60 days. Electrocardiography (under pentobarbital anaesthesia, 30
      mg/kg/dose), serologic immunofluorescence and microstrout were performed at the
      beginning and at the end of the treatment. Mice were sacrificed at day 10 after
      treatment; cardiac tissue was studied histopathologically and polymerase chain
      reaction (PCR) was performed. Spontaneous mortality was 30.43%, 3.85% and 4% in
      the control, trifluralin and benznidazole groups, respectively (significant
      survival, P=0.03). Microstrouts were negative in all three groups. Negative
      immunofluorescence titers were 0%, 16% (P=0.05) and 29% (P<0.02) in the control,
      trifluralin and benznidazole groups, respectively. The prevailing
      electrocardiographic disorder was prolongation of the PR interval in the control
      group, which was not significantly altered in trifluralin- and benznidazole
      treated mice, suggesting that trifluralin and benznidazole improve or even stop
      the damage caused by the disease on the conduction system. Trifluralin- and
      benznidazole-treated animals showed similar histologic patterns of myocarditis.
      PCR results were negative for benznidazole and trifluralin (100% and 70.8%,
      respectively). These results show the therapeutic potential of trifluralin in the
      treatment of chronic Chagas disease.

PMID- 16623858
TI  - The prevalence of suspected and challenge-verified penicillin allergy in a
      university hospital population.
AB  - Suspected penicillin allergy is common among hospitalised patients, but the
      quality of the information given by the patient is often doubtful. Alleged
      penicillin allergic are likely to be treated with more toxic, broad-spectrum, and
      more expensive antibiotics, with effects on microbial resistance patterns and
      public economy as a consequence. We performed a cross-sectional case-control
      study with two visits to all clinical departments of a large university hospital
      in order to find in-patients with medical files labelled "penicillin allergy" or
      who reported penicillin allergy upon admission. Patient histories were obtained
      via a questionnaire, and they were offered investigation for penicillin allergy
      with specific IgE, basophil histamine release, skin prick tests, intradermal
      tests and drug challenge tests. Finally, the pharmaco-economical consequences of
      the penicillin allergy were estimated. In a cohort of 3642 patients, 96 fulfilled
      the inclusion criteria giving a point-prevalence of alleged penicillin allergy of
      5% in a hospital in-patient population. Mean time elapsed since the alleged first
      reaction to penicillin was 20 years. The skin was the most frequently affected
      organ (82.2%), maculo-papular exanthema (35.4%) and urticaria (10.4%) being the
      most frequently reported reactions. 25% did not recall the time of their
      reaction. 82.2% did not remember the name of the penicillin they reacted to.
      34.8% had been treated with penicillins after suspicion of penicillin allergy had
      been raised. None of these reacted to penicillins. 33.3% of the patients
      receiving antibiotics during their current hospitalisation were prescribed
      penicillins. 2% developed non-severe exanthema. The average acquisition costs for
      antibiotics to penicillin allergic patients were euro 278, compared to euro 119
      had they been non-allergic. The prevalence of suspected penicillin allergy was
      lower than reported elsewhere. A substantial number of patients failed to recall
      basic information about their alleged allergy. Patients reporting penicillin
      allergy upon admission and labels stating penicillin allergy on medical files are
      ignored in almost a third of patients receiving antibiotics. The acquisition
      costs for antibiotics to penicillin allergic patients were higher, compared to
      the cost had the patients been non-allergic.

PMID- 16623859
TI  - Assessment by c-Fos immunostaining of changes in brain neural activity induced by
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and leptin in rats.
AB  - The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes
      multiple effects in laboratory animals. One of these is a wasting syndrome (a
      dramatic loss of body weight over 2-5 weeks) whose mechanism is still largely
      unknown. We exploited the over 1000 times difference in TCDD sensitivity between
      Long-Evans (Turku/AB); (L-E) and Han/Wistar (Kuopio); (H/W) rats to reveal brain
      areas that might be activated by a single dose of TCDD (50 microg/kg) given 24 hr
      previously. Leptin (1.3 mg/kg intraperitoneally 2 hr before tissue harvest) was
      used as a reference compound, as its neural pathway for decreasing food intake in
      the control of energy homeostasis is fairly well known. Serial sections of the
      brains were immunostained with an antibody for the activity marker c-Fos, and
      selected areas -- primarily in the hypothalamus -- were analysed with a computer
      assisted microscope. Given alone, TCDD did not elicit any major alterations in c
      Fos protein levels in the hypothalamic nuclei at the early time-point studied (24
      hr after administration), neither in pooled data nor in individual strains. The
      control substance leptin proved that the method is valid as it increased the
      number of c-Fos-immunopositive cells in the hypothalamic ventromedial and arcuate
      nuclei. Although the present findings are not suggestive of a primary role for
      the hypothalamus in the wasting syndrome, a time-course study covering also the
      feeding-active dark hours is warranted for their verification.

PMID- 16623860
TI  - Pharmacologic modulation of skeletal muscle metabolism: a microdialysis study.
AB  - Microdialysis is a valuable tool to measure tissue responses. We hypothesized
      that skeletal muscle metabolism can be modulated by microdialysis applied drugs
      which alter cytosolic calcium concentration. With approval of the local animal
      care committee, the hind limbs of sacrificed male Sprague Dawley rats were
      perfused either with Ringer's solution or with dantrolene 1 microM at 30 ml hr(
      1) and 21 degrees. Microdialysis probes in both hind limbs were perfused at 1
      microl min(-1) either with sorbitol 80 mM, calcium 20 mM, 40 mM, 80 mM, caffeine
      40 mM, 80 mM, and halothane 10 vol% respectively, and at the contralateral
      adductor muscle with Ringer as control. Lactate was measured
      spectrophotometrically in the dialysate at 15 min. intervals. Lactate levels as
      measured by intramuscular microdialysis were not influenced by intramuscular
      application of sorbitol 80 mM compared to control measurements with Ringer's
      solution. Local application of calcium 20 mM, 40 mM, 80 mM, caffeine 40 mM, 80
      mM, and halothane 10 vol% via microdialysis increased lactate concentrations,
      while organ perfusion by dantrolene 1 microM reduced the caffeine-induced lactate
      increase. Modulation of intramuscular lactate metabolism by exogenous compounds
      via microdialysis probes generates new insights in skeletal muscle metabolism.

PMID- 16623861
TI  - Neonatal jaundice and bilirubin UDP-glucuronosyl transferase 1A1 gene
      polymorphism in Turkish patients.
AB  - Bilirubin uridine diphosphate-glucuronosyltransferase (B-UGT) is the rate
      limiting enzyme for the conjugation of bilirubin with glucuronic acid in its
      excretion process into the bile. Variations in B-UGT gene (UGT-1A1) have been
      related to disorders characterised by hyperbilirubinaemia. The aim of this study
      was to investigate whether the number of thymine-adenine repeats in the promoter
      region of UGT-1A1 was related to non-physiologic hyperbilirubinemia of
      unexplained aetiology in Turkish newborns. These patients (n=106) were genotyped
      for their thymine-adenine repeat number in the promoter region of UGT-1A1, and
      were divided into two groups according to their bilirubin level. Forty-nine
      newborns with bilirubin levels higher than 17 mg/dl within the first ten days of
      life comprised the hyperbilirubinaemia group and 25 newborns with bilirubin
      levels higher than 10 mg/dl after fifteen days of life formed the prolonged
      jaundice group. Thirty-two newborns were included as healthy controls. The
      observed frequencies for the wild-type six repeat allele thymine-adenine (TA(6))
      within each subject group were similar (P>0.05; 75.5%, 78.0% and 73.4%,
      respectively). Likewise, the distribution of TA(6/6), TA(6/7) and TA(7/7)
      genotypes among three groups were similar. These results imply that the TA(7)
      repeat allele of UGT1A1 (UGT1A1*28) is a common variant in the Turkish
      population. Our results do not suggest an association between thymine-adenine
      repeat polymorphism of UGT1A1 and hyperbilirubinaemia of unexplained aetiology or
      prolonged jaundice in Turkish neonates.

PMID- 16623862
TI  - Choline-modulated arsenic trioxide-induced prolongation of cardiac repolarization
      in Guinea pig.
AB  - Arsenic trioxide (As(2)O(3)) has been found to be effective for relapsed or
      refractory acute promyelocytic leukaemia, but its clinical use is burdened by QT
      prolongation, Torsade de pointes tachycardias, and sudden cardiac death. The aim
      of the present study was to elucidate the ionic mechanisms of As(2)O(3)-induced
      abnormalities of cardiac electrophysiology and the therapeutic action of choline
      on As(2)O(3)-caused QT prolongation in guinea pig. Intravenous administration of
      As(2)O(3) prolonged the QT interval in a dose- and time-dependent manner in
      guinea pig hearts, and the QT prolongation could be modulated by choline. By
      using whole-cell patch clamp technique and confocal laser scanning microscopy, we
      found that As(2)O(3) significantly lengthened action potential duration measured
      at 50 and 90% of repolarization, enhanced L-type calcium currents (I(Ca-L)),
      inhibited delayed rectifier potassium currents (I(K)), and increased
      intracellular calcium concentration ([Ca(2+)](i)) in guinea pig ventricular
      myocytes. Choline corrected As(2)O(3)-mediated alterations of action potential
      duration, I(Ca-L) and [Ca(2+)](i), but had no effect on the I(K) inhibition.
      As(2)O(3) markedly disturbed the normal equilibrium of transmembrane currents
      (increasing I(Ca-L) and suppressing I(K)) in guinea pig cardiomyocyte, and
      induced prolongation of action potential duration, further degenerated into QT
      prolongation. Choline normalized QT interval abnormality and corrected lengthened
      action potential duration by inhibiting the elevated I(Ca-L) and [Ca(2+)](i) in
      ventricular myocytes during As(2)O(3) application.

PMID- 16623863
TI  - Russian VX: inhibition and reactivation of acetylcholinesterase compared with VX
      agent.
AB  - Organophosphorus compounds such as nerve agents inhibit, practically
      irreversibly, cholinesterases by their phosphorylation in the active site of
      these enzymes. Current antidotal treatment used in the case of acute nerve agent
      intoxications consists of combined administration of anticholinergic drug
      (usually atropine) and acetylcholinesterase (AChE, EC 3.1.1.7) reactivator (HI-6,
      obidoxime, pralidoxime), which from a chemical view is a derivative from the
      group of pyridinium or bispyridinium aldoximes (commonly called "oxime"). Oximes
      counteract acetylcholine increase, resulting from AChE inhibition. In the human
      body environment these compounds are powerful nucleophiles and are able to break
      down the bond between AChE and nerve agent molecule. This process leads to
      renewal of enzyme functionality -- to its reactivation. The usefulness of oxime
      in the reactivation process depends on its chemical structure and on the nerve
      agent whereby AChE is inhibited. Due to this fact, selection of suitable
      reactivator in the treatment of intoxications is very important. In our work, we
      have compared differences in the in vitro inhibition potency of VX and Russian VX
      on rat, pig and human brain, and subsequently we have tested reactivation of rat
      brain cholinesterase inhibited by these agents using oxime HI-6, obidoxime,
      pralidoxime, trimedoxime and methoxime. The results showed that no major
      differences in the reactivation process of both VX and Russian VX-inhibited
      cholinesterase. The similarity in reactivation was caused by analogous chemical
      structure of either nerve agent; and that oxime HI-6 seems to be the most
      effective reactivator tested, which confirms that HI-6 is currently the most
      potent reactivator of AChE inhibited by nerve agents. The results obtained in our
      study should be considered in the future development of new AChE reactivators.

PMID- 16623864
TI  - Toxic effects of lipid-mediated gene transfer in ventral mesencephalic explant
      cultures.
AB  - Adverse effects of cDNA and oligonucleotide delivery methods have not yet been
      systematically analyzed. We introduce a protocol to monitor toxic effects of two
      non-viral lipid-based gene delivery protocols using CNS primary tissue. Cell
      membrane damage was monitored by quantifying cellular uptake of propidium iodide
      and release of cytosolic lactate dehydrogenase to the culture medium. Using a
      liposomal transfection reagent, cell membrane damage was already seen 24 hr after
      transfection. Nestin-positive target cells, which were used as morphological
      correlate, were severely diminished in some areas of the cultures after liposomal
      transfection. In contrast, the non-liposomal transfection reagent revealed no
      signs of toxicity. This approach provides easily accessible information of
      transfection-associated toxicity and appears suitable for prescreening of
      transfection reagents.

PMID- 16623865
TI  - Generation of reactive oxygen species and induction of apoptosis of HL60 cells by
      ingredients of traditional herbal medicine, Sho-saiko-to.
AB  - The prooxidant and apoptosis-inducing effects of Sho-saiko-to, a traditional Sino
      Japanese herbal medicine and its active ingredients were analyzed. Among the
      components of Sho-saiko-to, wogon, the extract of Scutellaria and licorice root
      extract induced apoptosis of HL60 cells and increased the intracellular levels of
      reactive oxygen species. Lower concentrations (5 to 20 muM) of baicalein, the
      principal flavonoid in the Scutellaria root extract, showed induction of cell
      apoptosis and elevated the intracellular reactive oxygen species. However, the
      increase in the concentrations of baicalein rather inhibited the induction of
      apoptosis and the elevated levels of reactive oxygen species in cells. Induction
      of baicalein-mediated apoptosis was inhibited by addition of Tempol, the
      scavenger of reactive oxygen species. Glycyrrhetinic acid, an ingredient of
      licorice root extract, also induced apoptosis followed by increase in the
      intracellular reactive oxygen species. The effect of Sho-saiko-to on cell
      differentiation can be explained by the action of two ingredients, baicalein and
      glycyrrhetinic acid, which cause apoptosis and increase in reactive oxygen
      species in cells.

PMID- 16623866
TI  - Ultrastructural changes of the gemifloxacin on Achilles tendon in immature rats:
      comparison with those of ciproxacin and ofloxacin.
AB  - Gemifloxacin is a synthetic fluoroquinolone antimicrobial agent that exhibits
      potent activity against most Gram-negative and Gram-positive organisms, and has a
      comparatively low chondrotoxic potential in immature animals. This study examined
      the effects of gemifloxacin on the Achilles tendons in immature Sprague-Dawley
      rats treated by oral intubation once daily for 5 consecutive days from postnatal
      week 4 onward at doses of 0 (vehicle), and 600 mg/kg body weight. Ofloxacin or
      ciprofloxacin were used for comparison. The Achilles tendon specimens were
      examined by electron microscopy. In comparison with the vehicle-treated controls,
      there were ultrastructural changes in all samples from the gemifloxacin-,
      ofloxacin-, and ciprofloxacin-treated rats. Degenerative changes were observed in
      the tenocytes, and the cells that detached from the extracellular matrix were
      recognizable. The degree of degenerative changes and the number of degenerated
      cells in the Achilles tendon were significantly higher in the treated group than
      in the control group. Moreover, among the quinolone-treated groups, these
      findings were most significant in the ofloxacin-treated group, and least
      significant in the gemifloxacin-treated group. It is unclear what these findings
      mean with respect to the possible risk in juvenile patients treated with
      gemifloxacin or other quinolones. However, these results show that gemifloxacin
      causes less changes in the connective tissue structures.

PMID- 16623867
TI  - Ginsenoside Rh(2) enhances antitumour activity and decreases genotoxic effect of
      cyclophosphamide.
AB  - Ginsenoside Rh(2), a panaxadiol saponins, possesses various antitumour
      properties. Cyclophosphamide, an alkylating agent, has been shown to possess
      various genotoxic and carcinogenic effects, however, it is still used extensively
      as an antitumour agent and immunosuppressant in the clinic. Previous reports
      reveal that cyclophosphamide is involved in some secondary neoplasms. In this
      study, the antitumour activity and genotoxic effect of oral intake of ginsenoside
      Rh(2) combined with intraperitoneal injection of cyclophosphamide was
      investigated. Meanwhile, C57BL/6 mice bearing B16 melanoma and Lewis lung
      carcinoma cells were respectively used to estimate the antitumour activity in
      vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was
      assayed by frequency of micronucleus. The DNA damage in peripheral white blood
      cells was assayed by single cell gel electrophoresis as well. The results
      indicated that oral administration of Rh(2) (5, 10 and 20 mg/kg body weight)
      alone has no obvious antitumour activity and genotoxic effect in mice, while
      Rh(2) synergistically enhanced the antitumour activity of cyclophosphamide (40
      mg/kg body weight) in a dose-dependent manner. Rh(2) decreased the micronucleus
      formation in polychromatic erythrocytes and DNA strand breaks in white blood
      cells in a dose-dependent way. Our results suggest that ginsenoside Rh(2) is able
      to enhance the antitumour activity and decrease the genotoxic effect of
      cyclophosphamide.

PMID- 16623868
TI  - Effect of anandamide on cytosolic Ca(2+) levels and proliferation in canine renal
      tubular cells.
AB  - The effect of the endogenous cannabinoid anandamide on cytosolic free Ca(2+)
      concentration ([Ca(2+)](i)) and proliferation is largely unknown. This study
      examined whether anandamide altered Ca(2+) levels and caused Ca(2+)-dependent
      cell death in Madin-Darby canine kidney (MDCK) cells. [Ca(2+)](i) and cell death
      were measured using the fluorescent dyes fura-2 and WST-1 respectively.
      Anandamide at concentrations above 5 muM increased [Ca(2+)](i) in a concentration
      dependent manner. The Ca(2+) signal was reduced by 78% by removing extracellular
      Ca(2+). The anandamide-induced Ca(2+) influx was insensitive to L-type Ca(2+)
      channel blockers and the cannabinoid receptor antagonist AM 251, but was
      inhibited differently by aristolochic acid, WIN 55,212-2 (a cannabinoid receptor
      agonist), phorbol ester, GF 109203X and forskolin. After pretreatment with
      thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor), anandamide-induced
      Ca(2+) release was inhibited. Inhibition of phospholipase C with U73122 did not
      change anandamide-induced Ca(2+) release. At concentrations of 100 muM and 200
      muM, anandamide killed 50% and 95% cells, respectively. The cytotoxic effect of
      100 muM anandamide was completely reversed by pre-chelating cytosolic Ca(2+) with
      BAPTA. Collectively, in MDCK cells, anandamide induced [Ca(2+)](i) rises by
      causing Ca(2+) release from endoplasmic reticulum and Ca(2+) influx from
      extracellular space. Furthermore, anandamide can cause Ca(2+)-dependent
      cytotoxicity in a concentration-dependent manner.

PMID- 16623869
TI  - Veratridine-induced wet dog shake behaviour and apoptosis in rat hippocampus.
AB  - We have previously evaluated veratridine as an in vitro model of seizure using
      conventional electrophysiological recordings in rat hippocampal CA1 pyramidal
      neurones. The aim of this investigation is to further characterize this
      convulsant as an in vivo model of seizure. Veratridine was administered
      intraperitoneally to male Fisher rats in a dose range of 100-400 mug/kg. Within 5
      min. after the injections, the animals entered a quiescent period which was
      followed 10-15 min. later by facial automatism (washing), grooming, masticatory
      jaw movement and profuse salivation. This phenomenon was followed by the
      development of wet dog shake and forelimb clonus. The time (mean+/-S.E.M.) for
      the onset of induction of these shakes for all tested doses was 31.65+/-2.85 min.
      and the number of shakes (mean+/-S.E.M.) 30 min. after the onset was 17.2+/-2.85.
      The onset and number of wet dog shakes induced by veratridine was dose-dependent.
      No rat death was recorded until 2 weeks after the experiments. Histopathological
      studies of animals 2 weeks after veratridine administration showed evidence of
      apoptosis in the hippocampus. Our results indicate that veratridine produced a
      behavioural pattern of a limbic seizure which mimics temporal lobe epilepsy in
      man. Based on our previous findings in vitro and of this investigation in vivo,
      veratridine can be used as an experimental tool to evaluate potential
      antiepileptic drugs effective against this type of limbic behaviour.

PMID- 16623870
TI  - Modifying graft immunogenicity and immune response prior to transplantation:
      potential clinical applications of donor and graft treatment.
AB  - Many studies have shown a strong association between initial graft injury and
      poor long-term graft outcome. Events initiated by unspecific immune-activating
      processes including brain death and ischemia/reperfusion injury occurring prior
      to transplantation reduce graft functionality and amplify the host immune
      response. These events may be particularly relevant for less than optimal grafts
      with reduced resistance to unspecific injuries. Several approaches to ameliorate
      immune activation of the graft by treating the donor or the graft have been
      studied. While various substances have been shown to have protective effects in
      experimental transplantation, only a few drugs have been tested clinically and
      have demonstrated beneficial effects. We review the results of experimental and
      clinical studies on donor or graft immunomodulation prior to transplantation and
      analyze the evidence to support clinical application of these strategies.

PMID- 16623871
TI  - The influence of inherited and noninherited parental antigens on outcome after
      transplantation.
AB  - Contact between the immune systems of mother and child during pregnancy has an
      impact on transplantation later in life. Exposure to inherited paternal human
      leukocyte antigens (HLA) (IPA) and the noninherited maternal HLA antigens (NIMA)
      can lead to either immunization or tolerization. Exposure to IPA seems to have a
      more immunizing effect as the mature immune system of a mother can form anti-HLA
      antibodies against the foreign paternal HLA molecules. On the other hand,
      exposure of a child to the NIMA antigens during pregnancy may lead to NIMA
      specific tolerance. This review provides an overview of the current knowledge on
      the impact of this fetal-maternal interaction on the alloimmune response and
      clinical transplantation.

PMID- 16623872
TI  - Analysis of differences in outcome of two European liver transplant centers.
AB  - Authors analyzed the differences in the outcome of two European liver transplant
      centers differing in case volume and experience. The first was the
      Transplantation and Surgical Clinic, Semmelweis University, Budapest, Hungary
      (SEB) and the second the University Medical Center Groningen, Groningen, The
      Netherlands (UMCG). We investigated if such differences could be explained. The 1
      , 3- and 5-year patient survival in the UMCG was 86%, 80%, and 77% compared with
      65%, 56%, and 55% in SEB. Graft survival at the same time points was 79%, 71%,
      and 66% in the UMCG and 62%, 55%, and 53% in SEB. Significant differences were
      present regarding the donor and recipient age, diagnosis mix, disease severity
      and operation variables, per-operative transfusion rate, vascular complications,
      postoperative infection rate, and need for renal replacement. To determine
      factors correlating with survival, a separate uni- and multivariate analysis was
      performed in each center individually, between study parameters and patient
      survival. In both centers, peri-operative red blood cell (RBC) transfusion rate
      was a significant predictor for patient survival. The difference in blood loss
      can be explained by different operation techniques and shorter operation time in
      SEB, with consequently less time spent on hemostasis. It was jointly concluded
      that measures to reduce blood loss by adapting the operation technique might lead
      to improved survival and reduced morbidity.

PMID- 16623873
TI  - The place of liver transplantation in Caroli's disease and syndrome.
AB  - Caroli's disease (CD) or syndrome (CS) are rare inherited disorders which may
      cause severe, life-threatening, cholangitis or which may lead to hepatobiliary
      degeneration. The typical cystic biliary anomalies are often associated to
      congenital hepatic fibrosis (CHF) and, less frequently, to cystic renal disease
      especially autosomic recessive polycystic kidney disease (ARPKD). The place of
      liver transplantation (LT) in the treatment of CD or CS is evaluated based on our
      own experience of three successfully transplanted patients, the literature review
      of 19 patients and the European experience with 110 patients collected in the
      European Liver Transplant Registry. LT should be proposed as a definitive
      therapeutic option once severe cholangitis or (suspicion of) malignant
      transformation is present. The frequently used radiological, endoscopical or
      surgical biliary drainage procedures carry a high morbidity and mortality rate.
      In case of concomitant symptomatic CHF and renal failure, combined or sequential
      hepatorenal transplantation should be carried out, dependent on the evolution of
      the hepatic and renal disease. In case of associated ARPKD, renal transplantation
      is often indicated early on because of the more rapid progression of the renal
      component of the disease.

PMID- 16623874
TI  - Cyclosporine A versus tacrolimus monotherapy. Comparison on bile lipids in the
      first 3 months after liver transplant in humans.
AB  - Biliary lipids output is reduced after liver transplantation and tends to
      normalize thereafter. Cyclosporine A (CyA) is reported to interfere with the
      normal bile-restoring process after liver grafting, but data are inconclusive, in
      particular regarding the comparison with the other widely used calcineurin
      inhibitor tacrolimus (TCR). Furthermore, previous researches were conducted in
      patients taking multiple immunosuppressive therapies and with a short follow up.
      In this study we readdressed this issue by comparing biliary lipids in the first
      3 months after liver transplant, in 20 patients randomized to receive
      immunosuppression with CyA or TCR monotherapy. Bile samples, harvested through a
      T-tube at days 1, 3, 7, 15, 30, 60 and 90 were assessed for cholesterol,
      phospholipids, and total and individual concentrations of bile acids (BA). Liver
      and kidney function tests were evaluated as well. We found no differences between
      CyA and TCR in biochemical findings or in total biliary BAs, cholesterol, and
      phospholipids. However, CyA-treated patients showed lower levels of
      glycochenodeoxycholic acid at day 15, compared to those treated with TCR (P <
      0.04). This difference normalized thereafter, without any biochemical or clinical
      effect at 3-month follow up.

PMID- 16623875
TI  - Monotherapy with the vitamin D analogue MC1288 does not result in prolonged
      kidney allograft survival in rhesus monkeys.
AB  - The active form of vitamin D3, 1,25(OH)2D3, has pronounced immunoregulatory
      properties and is a potential treatment of immune-based disorders. However, the
      central role of this hormone in calcium and bone metabolism complicates its long
      term use as an immunomodulator. Some newly developed vitamin D3-derived
      analogues, such as MC1288, have an improved immunoregulatory potential and
      prolong allograft survival in rodent models. Such compounds might be a valuable
      component of immunosuppressive treatment regimen in transplantation and
      autoimmunity. The rhesus monkey provides a useful model for the preclinical
      validation of new therapeutic strategies for transplantation. The present study
      shows that MC1288 inhibits both proliferation and interferon-gamma production by
      rhesus peripheral blood mononuclear cells in a mixed lymphocyte reaction. We have
      tested the maximum tolerated dose of MC1288 in a rhesus monkey model of kidney
      transplantation. The observed effects on serum calcium and parathyroid hormone
      confirm the in vivo activity of MC1288. However, as a monotherapy, MC1288 did not
      cause prolongation of the kidney allograft survival in rhesus monkeys.

PMID- 16623876
TI  - Induction of regulatory T cells from mature T cells by allogeneic thymic
      epithelial cells in vitro.
AB  - The ability of thymic epithelial cells (TEC) to re-educate mature T cells to be
      regulatory T cells has not been addressed. In the present study, this issue was
      directly investigated by co-culturing of mature T cells and allo-TECs. B6
      macrophage cell line 1C21-cultured BALB/c splenocytes responded to B6 antigens in
      vitro. However, BALB/c splenocytes precultured with B6-derived TECs 1-4C18 or 1C6
      did not proliferate to B6 antigens, but responded to rat antigens. Exogenous
      interleukin-2 (IL-2) failed to revise the unresponsiveness of these T cells. Allo
      TEC-cultured T cells predominantly expressed Th2 cytokines (IL-4 and IL-10). B6
      TEC-cultured BALB/c splenocytes markedly inhibited the immune responses of naive
      BALB/c splenocytes to B6 antigens, but not to rat or the third-party mouse
      antigens. BALB/c nude mice that received naive syngeneic splenocytes rejected B6
      or rat skin grafts by 17 days postskin grafting; however, co-injection of B6 TEC
      cultured BALB/c splenocytes significantly delayed B6 skin graft rejection (P <
      0.01), with the unchanged rejection of rat skin grafts. These studies demonstrate
      that allo-TECs are able to 'educate' mature T cells to be regulatory cells, and
      suggest that regulatory cells derived from mature T cells by TECs may play an
      important role in T cell tolerance to allo- and auto-antigens.

PMID- 16623877
TI  - Ex vivo adenoviral gene transfer of constitutively activated STAT3 reduces post
      transplant liver injury and promotes regeneration in a 20% rat partial liver
      transplant model.
AB  - Signal transducer and activator of transcription-3 (STAT3) is one of the most
      important transcription factors for liver regeneration. This study was designed
      to examine the effects of constitutively activated STAT3 (STAT3-C) on post
      transplant liver injury and regeneration in a rat 20% partial liver transplant
      (PLTx) model by ex vivo adenoviral gene transfer. Adenovirus encoding the STAT3-C
      gene was introduced intraportally into liver grafts and clamped for 30 min during
      cold preservation. After orthotopic PLTx, liver graft/body weights and serum
      biochemistry were monitored, and both a histological study and DNA binding assay
      were performed. STAT3-C protein expression and its binding to DNA in the liver
      graft were confirmed by Western blotting and electrophoretic mobility shift assay
      (EMSA), respectively. This treatment modality promoted post-Tx liver regeneration
      effectively and rapidly. The serum levels of alanine aminotransferase/aspartate
      aminotransferase (AST/ALT) and bilirubin decreased in rats with STAT3-C. However,
      albumin (a marker of liver function) did not. Ex vivo gene transfer of STAT3-C to
      liver grafts reduced post-Tx injury and promoted liver regeneration. Thus, the
      activation of STAT3 in the liver graft may be a potentially effective clinical
      strategy for improving the outcome of small-for-size liver transplantation.

PMID- 16623878
TI  - Auxiliary partial orthotopic living donor liver transplantation in a patient with
      alcoholic liver cirrhosis to overcome donor steatosis.
AB  - The efficacy of auxiliary partial orthotopic liver transplantation (APOLT) to
      overcome the problems associated with a markedly steatotic graft in a living
      donor has not been fully explored. We have recently performed APOLT in a patient
      with alcoholic liver disease, where the only potential candidate donor was
      affected by 50% macrovesicular steatosis and 30% microvesicular steatosis. The
      recipient's left liver was resected and the donor's left liver, corresponding to
      a 0.46% graft-to-recipient weight ratio, was orthotopically transplanted. The
      postoperative course of this patient was uneventful, except for a transient large
      amount of ascites. Native liver volume in the recipient serially decreased, and
      the volume of the graft serially increased after transplantation. Four months
      after transplantation, the donor and recipient are doing well with a normal liver
      function. In conclusion, APOLT may be a feasible solution for a markedly
      steatotic living donor graft in patients with alcoholic liver disease.

PMID- 16623879
TI  - Colonic perforation associated with leukocytoclastic vasculitis caused by
      Sirolimus toxicity following renal transplantation.

PMID- 16623880
TI  - Sequential off-pump coronary artery bypass and liver transplantation.

PMID- 16623881
TI  - CYP707A3, a major ABA 8'-hydroxylase involved in dehydration and rehydration
      response in Arabidopsis thaliana.
AB  - Abscisic acid (ABA) catabolism is one of the determinants of endogenous ABA
      levels affecting numerous aspects of plant growth and abiotic stress responses.
      The major ABA catabolic pathway is triggered by ABA 8'-hydroxylation catalysed by
      the cytochrome P450 CYP707A family. Among four members of Arabidopsis CYP707As,
      the expression of CYP707A3 was most highly induced in response to both
      dehydration and subsequent rehydration. A T-DNA insertional cyp707a3-1 mutant
      contained higher ABA levels in turgid plants, which showed a reduced
      transpiration rate and hypersensitivity to exogenous ABA during early seedling
      growth. On dehydration, the cyp707a3-1 mutant accumulated a higher amount of
      stress-induced ABA than the wild type, an event that occurred relatively later
      and was coincident with slow drought induction of CYP707A3. The cyp707a3 mutant
      plants exhibited both exaggerated ABA-inducible gene expression and enhanced
      drought tolerance. Conversely, constitutive expression of CYP707A3 relieved
      growth retardation by ABA, increased transpiration, and a reduction of endogenous
      ABA in both turgid and dehydrated plants. Taken together, our results indicate
      that CYP707A3 plays an important role in determining threshold levels of ABA
      during dehydration and after rehydration.

PMID- 16623882
TI  - The Arabidopsis FLC protein interacts directly in vivo with SOC1 and FT chromatin
      and is part of a high-molecular-weight protein complex.
AB  - The Arabidopsis Flowering Locus C (FLC) protein is a repressor of flowering
      regulated by genes in the autonomous and vernalization pathways. Previous genetic
      and transgenic data have suggested that FLC acts by repressing expression of the
      floral integrator genes SOC1 and FT. We have taken an in vivo approach to
      determine whether the FLC protein interacts directly with potential DNA targets.
      Using chromatin immunoprecipitation, we have shown that FLC binds to a region of
      the first intron of FT that contains a putative CArG box, and have confirmed that
      FLC binds to a CArG box in the promoter of the SOC1 gene. MADS box proteins are
      thought to bind their DNA targets as dimers or higher-order multimers. We have
      shown that FLC is a component of a multimeric protein complex in vivo and that
      more than one FLC polypeptides can be present in the complex.

PMID- 16623883
TI  - Methylation of sulfhydryl groups: a new function for a family of small molecule
      plant O-methyltransferases.
AB  - In plants, type I and II S-adenosyl-l-methionine-dependent O-methyltransferases
      (OMTs) catalyze most hydroxyl group methylations of small molecules. A homology
      based RT-PCR strategy using Catharanthus roseus (Madagascar periwinkle) RNA
      previously identified six new type I plant OMT family members. We now describe
      the molecular and biochemical characterization of a seventh protein. It shares 56
      58% identity with caffeic acid OMTs (COMTs), but it failed to methylate COMT
      substrates, and had no activity with flavonoids. However, the in vitro
      incubations revealed unusually high background levels without added substrates. A
      search for the responsible component revealed that the enzyme methylated
      dithiothreitol (DTT), the reducing agent added for enzyme stabilization.
      Unexpectedly, product analysis revealed that the methylation occurred on a
      sulfhydryl moiety, not on a hydroxyl group. Analysis of 34 compounds indicated a
      broad substrate range, with a preference for small hydrophobic molecules. Benzene
      thiol (Km 220 microm) and furfuryl thiol (Km 60 microm) were the best substrates
      (6-7-fold better than DTT). Small isosteric hydrophobic substrates with hydroxyl
      groups, like phenol and guaiacol, were also methylated, but the activities were
      at least 5-fold lower than with thiols. The enzyme was named C. roseus S
      methyltransferase 1 (CrSMT1). Models based on the COMT crystal structure suggest
      that S-methylation is mechanistically identical to O-methylation. CrSMT1 so far
      is the only recognized example of an S-methyltransferase in this protein family.
      Its properties indicate that a few changes in key residues are sufficient to
      convert an OMT into a S-methyltransferase (SMT). Future functional investigations
      of plant methyltransferases should consider the possibility that the enzymes may
      direct methylation at sulfhydryl groups.

PMID- 16623884
TI  - Sequencing and characterization of telomere and subtelomere regions on rice
      chromosomes 1S, 2S, 2L, 6L, 7S, 7L and 8S.
AB  - Telomeres, which are important for chromosome maintenance, are composed of long,
      repetitive DNA sequences associated with a variety of telomere-binding proteins.
      We characterized the organization and structure of rice telomeres and adjacent
      subtelomere regions on the basis of cytogenetic and sequence analyses. The length
      of the rice telomeres ranged from 5.1 to 10.8 kb, as revealed by both fibre
      fluorescent in situ hybridization and terminal restriction-fragment assay.
      Physical maps of the chromosomal ends were constructed from a fosmid library.
      This facilitated sequencing of the telomere regions of chromosomes 1S, 2S, 2L,
      6L, 7S, 7L and 8S. The resulting sequences contained conserved TTTAGGG telomere
      repeats, which indicates that the physical maps partly covered the telomere
      regions of the respective chromosome arms. These repeats were organized in the
      order of 5'-TTTAGGG-3' from the chromosome-specific region, except in chromosome
      7S, in which seven inverted copies also existed in tandem array. Analysis of the
      telomere-flanking regions revealed the occurrence of deletions, insertions, or
      chromosome-specific substitutions of single nucleotides within the repeat
      sequences at the junction between the telomere and subtelomere. The sequences of
      the 500-kb regions of the seven chromosome ends were analysed in detail. A total
      of 598 genes were predicted in the telomeric regions. In addition, repetitive
      sequences derived from various kinds of retrotransposon were identified. No
      significant evidence for segmental duplication could be detected within or among
      the subtelomere regions. These results indicate that the rice chromosome ends are
      heterogeneous in both sequence and characterization.

PMID- 16623885
TI  - Transgressive segregation reveals two Arabidopsis TIR-NB-LRR resistance genes
      effective against Leptosphaeria maculans, causal agent of blackleg disease.
AB  - In a cross between the two resistant accessions Col-0 and Ler-0, a 15:1
      segregation was found in F2, suggesting the presence of unlinked resistance loci
      to Leptosphaeria maculans. One hundred Col-4 x Ler-0, and 50 Ler-2 x Cvi-1
      recombinant inbred lines, and seven susceptible Ler-0 x Ws-0 F2 progenies were
      examined to identify the two loci. Resistance in Col-4, Ws-0 and Cvi-1 (RLM1) was
      mapped to the marker m305 on chromosome 1. Col-4 x Ler-0 and Ler-2 x Cvi-1
      mapping populations located RLM2(Ler) on the same arm of chromosome 4. A tight
      physical location of RLM2 was established through near-isogenic lines. This
      region was found to correspond to an ancient duplication event between the RLM1
      and RLM2 loci. Two independent T-DNA mutants in a TIR-NB-LRR R gene (At1g64070)
      displayed susceptibility, and L. maculans susceptible mutant phenotypes were
      confirmed to be allelic for rlm1 in F1 after crosses with susceptible
      rlm1(Ler)rlm2(Col) plants. Complementation of rlm1(Ler)rlm2(Col) with the genomic
      Col-0 sequence of At1g64070 conferred resistance. In addition, two T-DNA mutants
      in a neighbouring homologous TIR-NB-LRR gene (At1g63880) displayed moderate
      susceptibility to L. maculans. Sequence analysis revealed that At1g64070 was
      truncated by a premature stop codon, and that At1g63880 was absent in Ler-0. RNA
      interference confirmed that Ler-0 resistance is dependent on genes structurally
      related to RLM1. Camalexin was identified as a quantitative co-dominant
      resistance factor of Col-0 origin, but independent of RLM1. RLM1/RLM2 resistance
      was, however, found to require RAR1 and partially HSP90.1.

PMID- 16623887
TI  - Conservation and divergence of plant microRNA genes.
AB  - MicroRNA (miRNA) is one class of newly identified, small, non-coding RNAs that
      play versatile and important roles in post-transcriptional gene regulation. All
      miRNAs have similar secondary hairpin structures; many of these are
      evolutionarily conserved. This suggests a powerful approach to predict the
      existence of new miRNA orthologs or homologs in other species. We developed a
      comprehensive strategy to identify new miRNA homologs by mining the repository of
      available ESTs. A total of 481 miRNAs, belonging to 37 miRNA families in 71
      different plant species, were identified from more than 6 million EST sequences
      in plants. The potential targets of the EST-predicted miRNAs were also elucidated
      from the EST and protein databases, providing additional evidence for the real
      existence of these miRNAs in the given plant species. Some plant miRNAs were
      physically clustered together, suggesting that these miRNAs have similar gene
      expression patterns and are transcribed together as a polycistron, as observed
      among animal miRNAs. The uracil nucleotide is dominant in the first position of
      5' mature miRNAs. Our results indicate that many miRNA families are
      evolutionarily conserved across all major lineages of plants, including mosses,
      gymnosperms, monocots and eudicots. Additionally, the number of miRNAs discovered
      was directly related to the number of available ESTs and not to evolutionary
      relatedness to Arabidopsis thaliana, indicating that miRNAs are conserved and
      little phylogenetic signal exists in the presence or absence of these miRNAs.
      Regulation of gene expression by miRNAs appears to have existed at the earliest
      stages of plant evolution and has been tightly constrained (functionally) for
      more than 425 million years.

PMID- 16623886
TI  - Interactions of two abscisic-acid induced WRKY genes in repressing gibberellin
      signaling in aleurone cells.
AB  - Gibberellins (GA) promote while abscisic acid (ABA) inhibits seed germination and
      post-germination growth. To address the cross-talk of GA and ABA signaling, we
      studied two rice WRKY genes (OsWRKY51 and OsWRKY71) that are ABA-inducible and GA
      repressible in embryos and aleurone cells. Over-expression of these two genes in
      aleurone cells specifically and synergistically represses induction of the ABA
      repressible and GA-inducible Amy32b alpha-amylase promoter reporter construct
      (Amy32b-GUS) by GA or the GA-inducible transcriptional activator, GAMYB. The
      physical interactions of OsWRKY71 proteins themselves and that of OsWRKY71 and
      OsWRKY51 are revealed in the nuclei of aleurone cells using bimolecular
      fluorescence complementation (BiFC) assays. Although OsWRKY51 itself does not
      bind to the Amy32b promoter in vitro, it interacts with OsWRKY71 and enhances the
      binding affinity of OsWRKY71 to W boxes in the Amy32b promoter. The binding
      activity of OsWRKY71 is abolished by deleting the C-terminus containing the WRKY
      domain or substituting the key amino acids in the WRKY motif and the zinc finger
      region. However, two of these non-DNA-binding mutants are still able to repress
      GA induction by enhancing the binding affinity of the wild-type DNA-binding
      OsWRKY71 repressors. In contrast, the third non-DNA-binding mutant enhances GA
      induction of Amy32b-GUS, by interfering with the binding of the wild-type
      OsWRKY71 or the OsWRKY71/OsWRKY51 repressing complex. These data demonstrate the
      synergistic interaction of ABA-inducible WRKY genes in regulating GAMYB-mediated
      GA signaling in aleurone cells, thereby establishing a novel mechanism for ABA
      and GA signaling cross-talk.

PMID- 16623888
TI  - Intracellular K+ sensing of SKOR, a Shaker-type K+ channel from Arabidopsis.
AB  - Most K+ channels in plants are structurally classified into the Shaker family
      named after the shaker K+ channel in Drosophila. Plant K+ channels function in
      many physiological processes including osmotic regulation and K+ nutrition. An
      outwardly rectifying K+ channel, SKOR, mediates the delivery of K+ from stelar
      cells to the xylem in the roots, a critical step in the long-distance
      distribution of K+ from roots to the upper parts of the plant. Here we report
      that SKOR channel activity is strictly dependent on intracellular K+
      concentrations. Activation by K+ did not affect the kinetics of voltage
      dependence in SKOR, indicating that a voltage-independent gating mechanism
      underlies the K+ sensing process. Further analysis showed that the C-terminal non
      transmembrane region of the SKOR protein was required for this sensing process.
      The intracellular K+ sensing mechanism couples SKOR activity to K+ nutrition
      status in the 'source cells', thereby establishing a supply-based unloading
      system for the regulation of K+ distribution.

PMID- 16623889
TI  - External K+ modulates the activity of the Arabidopsis potassium channel SKOR via
      an unusual mechanism.
AB  - Plant outward-rectifying K+ channels mediate K+ efflux from guard cells during
      stomatal closure and from root cells into the xylem for root-shoot allocation of
      potassium (K). Intriguingly, the gating of these channels depends on the
      extracellular K+ concentration, although the ions carrying the current are
      derived from inside the cell. This K+ dependence confers a sensitivity to the
      extracellular K+ concentration ([K+]) that ensures that the channels mediate K+
      efflux only, regardless of the [K+] prevailing outside. We investigated the
      mechanism of K+-dependent gating of the K+ channel SKOR of Arabidopsis by site
      directed mutagenesis. Mutations affecting the intrinsic K+ dependence of gating
      were found to cluster in the pore and within the sixth transmembrane helix (S6),
      identifying an 'S6 gating domain' deep within the membrane. Mapping the SKOR
      sequence to the crystal structure of the voltage-dependent K+ channel KvAP from
      Aeropyrum pernix suggested interaction between the S6 gating domain and the base
      of the pore helix, a prediction supported by mutations at this site. These
      results offer a unique insight into the molecular basis for a physiologically
      important K+-sensory process in plants.

PMID- 16623890
TI  - AtMBD9: a protein with a methyl-CpG-binding domain regulates flowering time and
      shoot branching in Arabidopsis.
AB  - The functional characterization of mammalian proteins containing a methyl-CpG
      binding domain (MBD) has revealed that MBD proteins can decipher the epigenetic
      information encoded by DNA methylation, and integrate DNA methylation,
      modification of chromatin structure and repression of gene expression. The
      Arabidopsis genome has 13 putative genes encoding MBD proteins, and no specific
      biological function has been defined for any AtMBD genes. In this study, we
      identified three T-DNA insertion mutant alleles at the AtMBD9 locus, and found
      that all of them exhibited obvious developmental abnormalities. First, the atmbd9
      mutants flowered significantly earlier than wild-type plants. The expression of
      FLOWERING LOCUS C (FLC), a major repressor of Arabidopsis flowering, was markedly
      attenuated by the AtMBD9 mutations. This FLC transcription reduction was
      associated with a significant decrease in the acetylation level in histone H3 and
      H4 of FLC chromatin in the atmbd9 mutants. Secondly, the atmbd9 mutants produced
      more shoot branches by increasing the outgrowth of axillary buds when compared
      with wild-type plants. The two known major factors controlling the outgrowth of
      axillary buds in Arabidopsis, auxin and the more axillary growth (MAX) pathway,
      were found not to be involved in producing this enhanced shoot branching
      phenotype in atmbd9 mutants, indicating that AtMBD9 may regulate a novel pathway
      to control shoot branching. This pathway is not related to FLC expression as over
      expression of FLC in atmbd9-2 restored its flowering time to one similar to that
      of the wild type, but did not alter the shoot branching phenotype.

PMID- 16623891
TI  - Production and characterization of auxin-insensitive rice by overexpression of a
      mutagenized rice IAA protein.
AB  - Since auxin was first isolated and characterized as a plant hormone, the
      underlying molecular mechanism of auxin signaling has been elucidated primarily
      in dicot plants represented by Arabidopsis. In monocot plants, the molecular
      mechanism of auxin signaling has remained unclear, despite various physiological
      experiments. To understand the function and mechanism of auxin signaling in rice
      (Oryza sativa), we focused on the IAA gene, a well-studied gene in Arabidopsis
      that serves as a negative regulator of auxin signaling. We found 24 IAA gene
      family members in the rice genome. OsIAA3 is one of these family members whose
      expression is rapidly increased in response to auxin. We produced transgenic rice
      harboring mOsIAA3-GR, which can overproduce mutant OsIAA3 protein containing an
      amino acid change in domain II to cause a gain-of-function phenotype, by
      treatment with dexamethasone. The transgenic rice was insensitive to auxin and
      gravitropic stimuli, and exhibited short leaf blades, reduced crown root
      formation, and abnormal leaf formation. These results suggest that, in rice,
      auxin is important for development and its signaling is mediated by IAA genes.

PMID- 16623892
TI  - An Arabidopsis cell wall-associated kinase required for invertase activity and
      cell growth.
AB  - The wall-associated kinases (WAK), a family of five proteins that contain
      extracellular domains that can be linked to pectin molecules of the cell wall,
      span the plasma membrane and have a cytoplasmic serine/threonine kinase domain.
      Previous work has shown that a reduction in WAK protein levels leads to a loss of
      cell expansion, indicating that these receptor-like proteins have a role in cell
      shape formation. Here it is shown that a single wak2 mutation exhibits a
      dependence on sugars and salts for seedling growth. This mutation also reduces
      the expression and activity of vacuolar invertase, often a key factor in turgor
      and expansion. WAKs may thus provide a molecular mechanism linking cell wall
      sensing (via pectin attachment) to regulation of solute metabolism, which in turn
      is known to be involved in turgor maintenance in growing cells.

PMID- 16623893
TI  - A mutation in the uvi4 gene promotes progression of endo-reduplication and
      confers increased tolerance towards ultraviolet B light.
AB  - We have isolated and characterized a new ultraviolet B (UV-B)-resistant mutant,
      uvi4 (UV-B-insensitive 4), of Arabidopsis. The fresh weight (FW) of uvi4 plants
      grown under supplemental UV-B light was more than twice that of the wild-type. No
      significant difference was found in their ability to repair the UV-B-induced
      cyclobutane pyrimidine dimers, or in the amount of UV-B absorptive compounds,
      both of which are well-known factors that contribute to UV sensitivity.
      Positional cloning revealed that the UVI4 gene encodes a novel basic protein of
      unknown function. We found that the hypocotyl cells in uvi4 undergo one extra
      round of endo-reduplication. The uvi4 mutation also promoted the progression of
      endo-reduplication during leaf development. The UVI4 gene is expressed mainly in
      actively dividing cells. In the leaves of P(UVI4)::GUS plants, the GUS signal
      disappeared in basipetal fashion as the leaf developed. The total leaf blade area
      was not different between uvi4 and the wild-type through leaf development, while
      the average cell area in the adaxial epidermis was considerably larger in uvi4,
      suggesting that the uvi4 leaves have fewer but larger epidermal cells. These
      results suggest that UVI4 is necessary for the maintenance of the mitotic state,
      and the loss of UVI4 function stimulated endo-reduplication. Tetraploid
      Arabidopsis was hyper-resistant to UV-B compared to diploid Arabidopsis,
      suggesting that the enhanced polyploidization is responsible for the increased UV
      B tolerance of the uvi4 mutant.

PMID- 16623894
TI  - Biolistic delivery of Ca2+ dyes into plant and algal cells.
AB  - In eukaryotes, changes in cytosolic Ca2+ concentrations ([Ca2+]cyt) are
      associated with a number of environmental and developmental stimuli. However,
      measuring [Ca2+]cyt changes in single plant or algal cells is often problematic.
      Although a wide range of Ca2+-sensitive fluorescent dyes is available, they are
      often difficult to introduce into plant cells. Micro-injection is the most robust
      method for dye loading, but is time-consuming, technically demanding, and
      unsuitable in many cell types. To overcome these problems, we have adapted
      biolistic techniques to load Ca2+-sensitive dyes into guard cells of the
      flowering plant, Commelina communis, cells of the green alga Chlamydomonas
      reinhardtii, and zygotes of the brown alga, Fucus serratus. Using this approach,
      we have been able to monitor [Ca2+]cyt changes in response to various stimuli,
      including a novel [Ca2+]cyt response in C. reinhardtii. The method allows the use
      of free acid and dextran-conjugated dyes. Biolistic loading of differentiated
      plant cells is easier, quicker, and more widely applicable than micro-injection,
      and should broaden the study of plant signal transduction.

PMID- 16623895
TI  - The Arabidopsis co-expression tool (ACT): a WWW-based tool and database for
      microarray-based gene expression analysis.
AB  - We present a new WWW-based tool for plant gene analysis, the Arabidopsis Co
      Expression Tool (ACT), based on a large Arabidopsis thaliana microarray data set
      obtained from the Nottingham Arabidopsis Stock Centre. The co-expression analysis
      tool allows users to identify genes whose expression patterns are correlated
      across selected experiments or the complete data set. Results are accompanied by
      estimates of the statistical significance of the correlation relationships,
      expressed as probability (P) and expectation (E) values. Additionally, highly
      ranked genes on a correlation list can be examined using the novel clique finder
      tool to determine the sets of genes most likely to be regulated in a similar
      manner. In combination, these tools offer three levels of analysis: creation of
      correlation lists of co-expressed genes, refinement of these lists using two
      dimensional scatter plots, and dissection into cliques of co-regulated genes. We
      illustrate the applications of the software by analysing genes encoding
      functionally related proteins, as well as pathways involved in plant responses to
      environmental stimuli. These analyses demonstrate novel biological relationships
      underlying the observed gene co-expression patterns. To demonstrate the ability
      of the software to develop testable hypotheses on gene function within a defined
      biological process we have used the example of cell wall biosynthesis genes. The
      resource is freely available at http://www.arabidopsis.leeds.ac.uk/ACT/

PMID- 16623898
TI  - Metabolomic approaches reveal that phosphatidic and phosphatidyl glycerol
      phospholipids are major discriminatory non-polar metabolites in responses by
      Brachypodium distachyon to challenge by Magnaporthe grisea.
AB  - Metabolomic approaches were used to elucidate some key metabolite changes
      occurring during interactions of Magnaporthe grisea--the cause of rice blast
      disease--with an alternate host, Brachypodium distachyon. Fourier-transform
      infrared (FT-IR) spectroscopy provided a high-throughput metabolic fingerprint of
      M. grisea interacting with the B. distachyon accessions ABR1 (susceptible) and
      ABR5 (resistant). Principal component-discriminant function analysis (PC-DFA)
      allowed the differentiation between developing disease symptoms and host
      resistance. Alignment of projected 'test-set' on to 'training-set' data indicated
      that our experimental approach produced highly reproducible data. Examination of
      PC-DFA loading plots indicated that fatty acids were one chemical group that
      discriminated between responses by ABR1 and ABR5 to M. grisea. To identify these,
      non-polar extracts of M. grisea-challenged B. distachyon were directly infused
      into an electrospray ionization mass spectrometer (ESI-MS). PC-DFA indicated that
      M. grisea-challenged ABR1 and ABR5 were differentially clustered away from
      healthy material. Subtraction spectra and PC-DFA loadings plots revealed
      discriminatory analytes (m/z) between each interaction and seven metabolites were
      subsequently identified as phospholipids (PLs) by ESI-MS-MS. Phosphatidyl
      glycerol (PG) PLs were suppressed during both resistant and susceptible
      responses. By contrast, different phosphatidic acid PLs either increased or were
      reduced during resistance or during disease development. This suggests
      considerable and differential PL processing of membrane lipids during each
      interaction which may be associated with the elaboration/suppression of defence
      mechanisms or developing disease symptoms.

PMID- 16623899
TI  - A tomato mutant that shows stunting, wilting, progressive necrosis and
      constitutive expression of defence genes contains a recombinant Hcr9 gene
      encoding an autoactive protein.
AB  - The tomato Cf-9 gene confers resistance to races of the leaf mould fungus
      Cladosporium fulvum that carry the Avr9 avirulence gene. Cf-9 resides at a locus
      containing five paralogous genes and was isolated by transposon tagging using a
      modified maize Dissociation (Ds) element. The tagging experiment generated an
      allelic series of Ds-induced mutations of Cf-9, most of which were wild type in
      appearance. However, one mutant, designated M205, showed stunted growth, wilting,
      progressive leaf chlorosis and necrosis and constitutive expression of defence
      genes. The phenotype of M205 was caused by a semidominant, Avr9-independent
      mutation that co-segregated with a Ds element insertion at the Cf-9 locus.
      Molecular genetic analysis indicated that the Cf-9 locus of M205 had undergone
      recombination, generating a chimeric gene, designated Hcr9-M205, that comprised
      an in-frame fusion between the 5' coding region of the Cf-9 paralogue, Hcr9-9A,
      and the 3' coding region of Cf-9. The presence of a possible excision footprint
      adjacent to the junction between Hcr9-9A and Cf-9, and a Ds insertion at the
      homologous position in the downstream paralogue Hcr9-9D, is consistent with
      recombination between Hcr9-9A and Cf-9 promoted by transposition of Ds from Cf-9
      into Hcr9-9D. Agrobacterium tumefaciens-mediated transient expression of Hcr9
      M205 in Nicotiana tabacum caused chlorosis and the accumulation of defence gene
      transcripts, indicating that the protein encoded by this novel Hcr9 gene is
      autoactive.

PMID- 16623900
TI  - Dominant-negative interference with defence signalling by truncation mutations of
      the tomato Cf-9 disease resistance gene.
AB  - The tomato Cf-9 gene confers resistance to races of the leaf mould fungus
      Cladosporium fulvum that carry the Avr9 avirulence gene. Cf-9 was isolated by
      transposon tagging using a modified maize Dissociation (Ds) element. This
      generated an allelic series of Ds-induced mutations of Cf-9, of which two were
      found to confer novel phenotypes in a screen for mutants affecting wild-type Cf-9
      function in trans. Genetic and molecular analysis of these mutants suggested
      semidominant, Avr9-dependent, negative-interfering mutations involving Ds
      insertions in a defined subregion of Cf-9. Interference was associated with
      expression of the 5'-end of Cf-9 upstream of the Ds insertions in these mutants,
      suggesting that truncated Cf-9 proteins were the likely cause of interference.
      Transgenic tomato lines harbouring Cf-9 constructs with premature stop codons in
      positions similar to the Ds insertions also showed interference, indicating that
      the presence of Ds was not required for interference to occur. Interestingly,
      interference in these transgenic lines was completely dominant and was associated
      with a pronounced developmental phenotype that was dependent on co-expression of
      Cf-9, Avr9 and a truncated Cf-9 transgene. However, interference with a weakly
      autoactive Hcr9 gene was Avr9-independent and did not cause a developmental
      phenotype, suggesting that localized restoration of Cf-9/Avr9-dependent cell
      death was responsible for the developmental phenotype. The restricted region in
      which truncation of Cf-9 results in dominant-negative interference suggests that
      leucine-rich repeats (LRR) 16-19 of Cf-9 may mediate dimerization of Cf-9 and
      LRRs 20-23 may mediate interactions with downstream partner proteins required for
      Cf-9 signalling, or vice versa.

PMID- 16623901
TI  - A chloroplast-localized dual-specificity protein phosphatase in Arabidopsis
      contains a phylogenetically dispersed and ancient carbohydrate-binding domain,
      which binds the polysaccharide starch.
AB  - Dual-specificity protein phosphatases (DSPs) are important regulators of a wide
      variety of protein kinase signaling cascades in animals, fungi and plants. We
      previously identified a cluster of putative DSPs in Arabidopsis (including
      At3g52180 and At3g01510) in which the phosphatase domain is related to that of
      laforin, the human protein mutated in Lafora epilepsy. In animal and fungal
      systems, the laforin DSP and the beta-regulatory subunits of AMP-regulated
      protein kinase (AMPK) and Snf-1 have all been demonstrated to bind to glycogen by
      a glycogen-binding domain (GBD). We present a bioinformatic analysis which shows
      that these DSPs from Arabidopsis, together with other related plant DSPs, share
      with the above animal and fungal proteins a widespread and ancient carbohydrate
      binding domain. We demonstrate that DSP At3g52180 binds to purified starch
      through its predicted carbohydrate-binding region, and that mutation of key
      conserved residues reduces this binding. Consistent with its ability to bind
      exogenous starch, DSP At3g52180 was found associated with starch purified from
      Arabidopsis plants and suspension cells. Immunolocalization experiments revealed
      a co-localization with chlorophyll, placing DSP At3g52180 in the chloroplast.
      Gene-expression data from different stages of the light-dark cycle and across a
      wide variety of tissues show a strong correlation between the pattern displayed
      by transcripts of the At3g52180 locus and that of genes encoding key starch
      degradative enzymes. Taken together, these data suggest the hypothesis that plant
      DSPs could be part of a protein assemblage at the starch granule, where they
      would be ideally situated to regulate starch metabolism through reversible
      phosphorylation events.

PMID- 16623902
TI  - Identification and functional analysis of a prokaryotic-type aspartate
      aminotransferase: implications for plant amino acid metabolism.
AB  - In this paper, we report the identification of genes from pine (PpAAT),
      Arabidopsis (AtAAT) and rice (OsAAT) encoding a novel class of aspartate
      aminotransferase (AAT, EC 2.6.1.1) in plants. The enzyme is unrelated to other
      eukaryotic AATs from plants and animals but similar to bacterial enzymes.
      Phylogenetic analysis indicates that this prokaryotic-type AAT is closely related
      to cyanobacterial enzymes, suggesting it might have an endosymbiotic origin.
      Interestingly, most of the essential residues involved in the interaction with
      the substrate and the attachment of pyridoxal phosphate cofactor in the active
      site of the enzyme were conserved in the deduced polypeptide. The polypeptide is
      processed in planta to a mature subunit of 45 kDa that is immunologically
      distinct from the cytosolic, mitochondrial and chloroplastic isoforms of AAT
      previously characterized in plants. Functional expression of PpAAT sequences in
      Escherichia coli showed that the processed precursor is assembled into a
      catalytically active homodimeric holoenzyme that is strictly specific for
      aspartate. These atypical genes are predominantly expressed in green tissues of
      pine, Arabidopsis and rice, suggesting a key role of this AAT in nitrogen
      metabolism associated with photosynthetic activity. Moreover, immunological
      analyses revealed that the plant prokaryotic-type AAT is a nuclear-encoded
      chloroplast protein. This implies that two plastidic AAT co-exist in plants: a
      eukaryotic type previously characterized and the prokaryotic type described here.
      The respective roles of these two enzymes in plant amino acid metabolism are
      discussed.

PMID- 16623903
TI  - Evidence for folate-salvage reactions in plants.
AB  - Folates in vivo undergo oxidative cleavage, giving pterin and p
      aminobenzoylglutamate (pABAGlu) moieties. These breakdown products are excreted
      in animals, but their fate is unclear in microorganisms and unknown in plants. As
      indirect evidence from this and previous studies strongly suggests that plants
      can have high folate-breakdown rates (approximately 10% per day), salvage of the
      cleavage products seems likely. Four sets of observations support this
      possibility. First, cleavage products do not normally accumulate: pools of
      pABAGlu (including its polyglutamyl forms) are equivalent to, at most, 4-14% of
      typical total folate pools in Arabidopsis thaliana, Lycopersicon esculentum and
      Pisum sativum tissues. Pools of the pterin oxidation end-product pterin-6
      carboxylate are, likewise, fairly small (3-37%) relative to total folate pools.
      Second, little pABAGlu built up in A. thaliana plantlets when net folate
      breakdown was induced by blocking folate synthesis with sulfanilamide. Third, A.
      thaliana and L. esculentum tissues readily converted supplied breakdown products
      to folate synthesis precursors: pABAGlu was hydrolysed to p-aminobenzoate and
      glutamate, and dihydropterin-6-aldehyde was reduced to 6
      hydroxymethyldihydropterin. Fourth, both these reactions were detected in vitro;
      the reduction used NADPH as cofactor. An alternative salvage route for pABAGlu,
      direct reincorporation into dihydrofolate via the action of dihydropteroate
      synthase, appears implausible from the properties of this enzyme. We conclude
      that plants are excellent organisms in which to explore the biochemistry of
      folate salvage.

PMID- 16623904
TI  - Mutations in the Diageotropica (Dgt) gene uncouple patterned cell division during
      lateral root initiation from proliferative cell division in the pericycle.
AB  - In angiosperms, root branching requires a continuous re-initiation of new root
      meristems. Through some unknown mechanism, in most eudicots pericycle cells
      positioned against the protoxylem change identity and initiate patterned
      division, leading to formation of lateral root primordia that further develop
      into lateral roots. This process is auxin-regulated. We have observed that three
      mutations in the Diageotropica (Dgt) gene in tomato prevent primordium formation.
      Detailed analysis of one of these mutants, dgt1-1, demonstrated that the mutation
      does not abolish the proliferative capacity of the xylem-adjacent pericycle in
      the differentiated root portion. Files of shortened pericycle cells found in dgt1
      1 roots were unrelated to primordium formation. Auxin application stimulated this
      unusual proliferation, leading to formation of a multi-layered xylem-adjacent
      pericycle, but did not rescue the primordium formation. In contrast to wild type,
      auxin could not induce any cell divisions in the pericycle of the most distal
      dgt1-1 root-tip portion. In wild-type roots, the Dgt gene promoter was expressed
      strongly in lateral root primordia starting from their initiation, and on auxin
      treatment was induced in the primary root meristem. Auxin level and distribution
      were altered in dgt1-1 root tissues, as judged by direct auxin measurements, and
      the tissue-specific expression of an auxin-response reporter was altered in
      transgenic plants. Together, our data demonstrate that the Dgt gene product, a
      type-A cyclophilin, is essential for morphogenesis of lateral root primordia, and
      that the dgt mutations uncouple patterned cell division in lateral root
      initiation from proliferative cell division in the pericycle.

PMID- 16623905
TI  - Nuclear suppressors define three factors that participate in both 5' and 3' end
      processing of mRNAs in Chlamydomonas chloroplasts.
AB  - Chloroplast RNA processing and degradation are orchestrated by nucleus-encoded
      factors. Although several transcript-specific factors have been identified, those
      involved in global RNA metabolism have mostly remained elusive. Using
      Chlamydomonas reinhardtii, we have identified three pleiotropic nuclear
      mutations, mcd3, mcd4 and mcd5, which cause quantitative variation between
      polycistronic transcripts and accumulation of transcripts with novel 3' ends. The
      mcd3, mcd4 and mcd5 mutants were initially isolated as photoautotrophic
      suppressors of the petD 5' mutants LS2 and LS6, which harbour four nucleotide
      linker-scanning mutations near the 5' end of the mature transcript. The LS
      mutants accumulate 1-3% of the wild-type (WT) petD mRNA level and no cytochrome
      b6/f complex subunit IV, which is the petD gene product and required for
      photosynthesis. Each suppressor restores approximately 15% of the WT petD mRNA
      and subunit IV levels. Genetic analysis showed mcd4 to be recessive, and
      suggested that MCD4 interacts with the petD mRNA stability factor MCD1. To assess
      the specificity of mcd3, mcd4 and mcd5, transcripts from 32 chloroplast genes
      were analysed by RNA filter hybridizations. mcd3 and mcd4 displayed aberrant
      transcript patterns for 17 genes, whereas only three were altered in mcd5. Since
      the mutations affect multiple RNAs in a variety of ways, our data suggest that
      MCD3, MCD4 and MCD5 may participate in a series of multiprotein complexes
      responsible for RNA maturation and degradation in Chlamydomonas chloroplasts.

PMID- 16623906
TI  - The CCAAT binding factor can mediate interactions between CONSTANS-like proteins
      and DNA.
AB  - CONSTANS-Like (COL) proteins are plant-specific nuclear regulators of gene
      expression but do not contain a known DNA-binding motif. We tested whether a
      common DNA-binding protein can deliver these proteins to specific cis-acting
      elements. We screened for proteins that interact with two members of a subgroup
      of COL proteins. These COL proteins were Tomato COL1 (TCOL1), which does not seem
      to be involved in the control of flowering time, and the Arabidopsis thaliana
      CONSTANS (AtCO) protein which mediates photoperiodic induction of flowering. We
      show that the C-terminal plant-specific CCT (CO, CO-like, TIMING OF CAB
      EXPRESSION 1) domain of both proteins binds the trimeric CCAAT binding factor
      (CBF) via its HAP5/NF-YC component. Chromatin immunoprecipitation demonstrated
      that TCOL is recruited to the CCAAT motifs of the yeast CYC1 and HEM1 promoters
      by HAP5. In Arabidopsis, each of the three CBF components is encoded by several
      different genes that are highly transcribed. Under warm long days, high levels of
      expression of a tomato HAP5 (THAP5a) gene can reduce the flowering time of
      Arabidopsis. A mutation in the CCT domain of TCOL1 disrupts the interaction with
      THAP5 and the analogous mutation in AtCO impairs its function and delays
      flowering. CBFs are therefore likely to recruit COL proteins to their DNA target
      motifs in planta.

PMID- 16623907
TI  - WRKY70 modulates the selection of signaling pathways in plant defense.
AB  - Cross-talk between signal transduction pathways is a central feature of the
      tightly regulated plant defense signaling network. The potential synergism or
      antagonism between defense pathways is determined by recognition of the type of
      pathogen or pathogen-derived elicitor. Our studies have identified WRKY70 as a
      node of convergence for integrating salicylic acid (SA)- and jasmonic acid (JA)
      mediated signaling events during plant response to bacterial pathogens. Here, we
      challenged transgenic plants altered in WRKY70 expression as well as WRKY70
      knockout mutants of Arabidopsis with the fungal pathogens Alternaria brassicicola
      and Erysiphe cichoracearum to elucidate the role of WRKY70 in modulating the
      balance between distinct defense responses. Gain or loss of WRKY70 function
      causes opposite effects on JA-mediated resistance to A. brassicicola and the SA
      mediated resistance to E. cichoracearum. While the up-regulation of WRKY70 caused
      enhanced resistance to E. cichoracearum, it compromised plant resistance to A.
      brassicicola. Conversely, down-regulation or insertional inactivation of WRKY70
      impaired plant resistance to E. cichoracearum. Over-expression of WRKY70 resulted
      in the suppression of several JA responses including expression of a subset of JA
      and A. brassicicola-responsive genes. We show that this WRKY70-controlled
      suppression of JA-signaling is partly executed by NPR1. The results indicate that
      WRKY70 has a pivotal role in determining the balance between SA-dependent and JA
      dependent defense pathways.

PMID- 16623908
TI  - Use of the glucosyltransferase UGT71B6 to disturb abscisic acid homeostasis in
      Arabidopsis thaliana.
AB  - A glucosyltransferase (GT) of Arabidopsis, UGT71B6, recognizing the naturally
      occurring enantiomer of abscisic acid (ABA) in vitro, has been used to disturb
      ABA homeostasis in planta. Transgenic plants constitutively overexpressing
      UGT71B6 (71B6-OE) have been analysed for changes in ABA and the related ABA
      metabolites abscisic acid glucose ester (ABA-GE), phaseic acid (PA),
      dihydrophaseic acid (DPA), 7'-hydroxyABA and neo-phaseic acid. Overexpression of
      the GT led to massive accumulation of ABA-GE and reduced levels of the oxidative
      metabolites PA and DPA, but had marginal effect on levels of free ABA. The
      control of ABA homeostasis, as reflected in levels of the different metabolites,
      differed in the 71B6-OEs whether the plants were grown under standard conditions
      or subjected to wilt stress. The impact of increased glucosylation of ABA on ABA
      related phenotypes has also been assessed. Increased glucosylation of ABA led to
      phenotypic changes in post-germinative growth. The use of two structural
      analogues of ABA, known to have biological activity but to differ in their
      capacity to act as substrates for 71B6 in vitro, confirmed that the phenotypic
      changes arose specifically from the increased glucosylation caused by
      overexpression of 71B6. The phenotype and profile of ABA and related metabolites
      in a knockout line of 71B6, relative to wild type, has been assessed during
      Arabidopsis development and following stress treatments. The lack of major
      changes in these parameters is discussed in the context of functional redundancy
      of the multigene family of GTs in Arabidopsis.

PMID- 16623909
TI  - Genome-wide analysis of spatial and temporal gene expression in rice panicle
      development.
AB  - The basic structure of a rice inflorescence (the panicle) is determined by the
      pattern of branch formation, which is established at the early stages of panicle
      development. In this study we conducted global transcriptome profiling of the
      early stages of rice panicle development from phase transition to floral organ
      differentiation. To generate a meristem-specific gene-expression profile, shoot
      apical meristems (SAMs) and subsequently formed, very young panicles were
      collected manually and used for cDNA microarray analysis. We identified 357 out
      of 22,000 genes that are expressed differentially in the early stages of panicle
      development, and the 357 genes were classified into seven groups based on their
      temporal expression patterns. The most noticeable feature is that a fairly small
      number of genes, which are extensively enriched in transcription factors, are
      upregulated in the SAM immediately after phase transition. In situ hybridization
      analysis showed that each gene analysed exhibits a unique and interesting
      localization of mRNA. Remarkably, one of the transcription factors was proven to
      be a close downstream component of the pathway in which LAX, a major regulator of
      panicle branching, acts. These results suggest that our strategy--careful
      collection of meristems, global transcriptome analysis and subsequent in situ
      hybridization analysis--is useful not only to obtain a genome-wide view of gene
      expression, but also to reveal genetic networks controlling rice panicle
      development.

PMID- 16623910
TI  - Arabidopsis homologue of human transcription factor IIH/nucleotide excision
      repair factor p44 can function in transcription and DNA repair and interacts with
      AtXPD.
AB  - Eukaryotic general transcription factor (TF) IIH is composed of 10 proteins,
      seven of which are also required for nucleotide excision repair (NER) of UV
      radiation-induced DNA damage in human cells and yeast. Plant homologues of the
      human TFIIH subunits XPB and XPD that function in NER have been isolated but none
      has been shown to operate in transcription. Here we address the capabilities of
      Arabidopsis thaliana AtGTF2H2 and AtXPD, homologues of the essential interacting
      human/yeast TFIIH components p44/Ssl1 and XPD/Rad3, respectively. Expression of
      AtGTF2H2 or AtXPD cDNAs in yeast ssl1 or rad3 mutants temperature-sensitive for
      growth due to thermolabile transcription of mRNA restored growth and so
      transcription at the non-permissive temperature. AtGTF2H2 also complemented the
      NER deficiency of the corresponding yeast mutant, as measured by full recovery of
      UV resistance, whereas AtXPD did not despite being necessary for NER in
      Arabidopsis. UV treatment did not upregulate transcription of AtGTF2H2 or AtXPD
      in Arabidopsis. Suppression of a yeast translation initiation defect by the ssl1
      1 mutation was prevented by expression of AtGTF2H2. Deletion of SSL1 in a yeast
      strain expressing AtGTF2H2 did not affect growth or confer UV sensitivity,
      demonstrating that AtGTF2H2 can perform all essential transcription functions and
      UV damage repair duties of Ssl1 in its absence. Furthermore, AtGTF2H2 interacted
      with AtXPD and yeast Rad3, and AtXPD also interacted with yeast Ssl1 in two
      hybrid assays. Our results indicate that AtGTF2H2 can act in transcription and
      NER, and suggest that it participates in both processes in Arabidopsis as part of
      TFIIH.

PMID- 16623911
TI  - ABERRANT TESTA SHAPE encodes a KANADI family member, linking polarity
      determination to separation and growth of Arabidopsis ovule integuments.
AB  - The Arabidopsis aberrant testa shape (ats) mutant produces a single integument
      instead of the two integuments seen in wild-type ovules. Cellular anatomy and
      patterns of marker gene expression indicate that the single integument results
      from congenital fusion of the two integuments of the wild type. Isolation of the
      ATS locus showed it to encode a member of the KANADI (KAN) family of putative
      transcription factors, previously referred to as KAN4. ATS was expressed at the
      border between the two integuments at the time of their initiation, with
      expression later confined to the abaxial layer of the inner integument. In an
      inner no outer (ino) mutant background, where an outer integument does not form,
      the ats mutation led to amorphous inner integument growth. The kan1kan2 double
      mutant exhibits a similar amorphous growth of the outer integument without
      affecting inner integument growth. We hypothesize that ATS and KAN1/KAN2 play
      similar roles in the specification of polarity in the inner and outer
      integuments, respectively, that parallel the known roles of KAN proteins in
      promoting abaxial identity during leaf development. INO and other members of the
      YABBY gene family have been hypothesized to have similar parallel roles in outer
      integument and leaf development. Together, these two hypotheses lead us to
      propose a model for normal integument growth that also explains the described
      mutant phenotypes.

PMID- 16623913
TI  - Transfusion-transmitted hepatitis E in a 'nonhyperendemic' country.
AB  - Indigenous hepatitis E is increasingly recognized in developed countries, where
      it may be a zoonosis. We describe the first case of transfusion-transmitted
      hepatitis E in the UK from a blood donor who had no history of recent travel
      abroad. Follow-up of the donor and recipients of the blood products was carried
      out using serological and molecular techniques. Acute hepatitis E was transmitted
      to one of two recipients. The infected patient would have received a larger
      volume of the donor's plasma. HEV subgenomic sequences carried by the donor and
      recipient were identical. This is the first case of post-transfusion hepatitis E
      in the UK. Secondary transmission of hepatitis E indigenous to a nonhyperendemic
      country may occur by blood transfusion. It is important that blood donors inform
      the transfusion service of all post-donation illnesses so that appropriate
      interventions can take place.

PMID- 16623914
TI  - Solvent-detergent plasma: use in neonatal patients, in adult and paediatric
      patients with liver disease and in obstetric and gynaecological emergencies.
AB  - The study was conducted to assess the efficacy and tolerance of solvent-detergent
      (SD) plasma in neonates, in obstetric and gynaecological patients and in patients
      with liver disease in three large hospitals in Dublin during the period 1 April
      2002 (when SD plasma was introduced) through 31 October 2003. Forty-one neonates
      received 67 transfusions of SD plasma at a mean dose +/- standard deviation of
      18.4 +/- 13.2 mL kg(-1). Thirty-one (75.6%) patients had coagulopathy without
      haemorrhage (either disseminated intravascular coagulopathy or other
      coagulopathy); a further eight (19.5%) had clinical haemorrhage (excluding
      intraventricular haemorrhage), which complicated a coagulopathy. Thirty-eight
      obstetric and gynaecological patients received 57 SD plasma transfusions at a
      mean dose of 15.3 +/- 7.7 mL kg(-1). Thirty-six women (94.7%) had haemorrhage
      with mean blood loss per patient of 3345.8 +/- 2738.1 mL. Fifteen children with
      liver disease received 33 SD plasma transfusions at a mean volume of 38.0 +/-
      41.5 mL kg(-1) body weight. Seventeen adult patients with severe end-stage liver
      disease were transfused with SD plasma either following liver transplantation or
      prior to other invasive procedures, at a mean dose of 10.2 +/- 3.4 mL kg(-1).
      There were statistically significant decreases in mean activated partial
      thromboplastin time and prothrombin time in neonates, in obstetric and
      gynaecological patients and in patients with liver disease. Complete correction
      of coagulation parameters was not achieved in any case in the liver transplant
      group. No adverse reactions were observed for SD plasma infusion. Use of SD
      plasma in critically ill neonates, in women with obstetric and gynaecological
      emergencies and in patients with liver disease appears safe, and improves
      laboratory indices of coagulopathy.

PMID- 16623915
TI  - Recombinant factor VIIa reduces transfusion requirements in liver transplant
      patients with high MELD scores.
AB  - Patients undergoing orthotopic liver transplantation (OLT) often experience
      significant coagulopathy and remain at risk for excessive blood loss and massive
      transfusion. The ability of recombinant factor VIIa (rFVIIa) to reduce
      transfusion requirements during OLT has not been well established. This
      retrospective study investigates whether rFVIIa reduces transfusion requirements
      in liver transplant patients with a significantly prolonged prothrombin time (PT)
      and a model of end-stage liver disease (MELD) score of > 20. Eleven patients
      received a single dose of rFVIIa (58 +/- 18 microg kg(-1)) at the time of
      incision. This group was matched with a selected control group that fulfilled all
      of the inclusion/exclusion criteria. Patient characteristics, pre-operative PT,
      HCT, PLT and MELD were identical between groups. Prophylactic application of
      rFVIIA reduced packed red blood cells (3.9 +/- 2.6 versus 6.9 +/- 2.3 U, P =
      0.01) and fresh-frozen plasma (FFP) (12.6 +/- 6 versus 19.8 +/- 7 U, P = 0.018)
      transfusion requirements when compared with the control group. FFP administration
      in the first 24 h after surgery was also significantly less in the rVIIa group
      when compared with the control group (388 +/- 385 versus 1225 +/- 701 mL, P =
      0.003). Hospital stay following transplantation tended to be shorter in the
      rFVIIa group, albeit statistical significance was not achieved (11 +/- 7.3 versus
      7.9 +/- 2.7, P = 0.2). All but one patient in the control group survived for 30
      days after transplantation. In a selected group of patients with prolonged PT and
      high MELD score, the prophylactic application of rFVIIa at the start of the OLT
      may reduce perioperative transfusion requirements.

PMID- 16623916
TI  - Immature platelet fraction measurement: a future guide to platelet transfusion
      requirement after haematopoietic stem cell transplantation.
AB  - summary. The decision to prophylactically transfuse platelets is dependent on the
      platelet count, careful regular clinical assessment and agreed local protocol.
      The ability to predict when platelet recovery will occur should allow a more
      reasoned approach to platelet transfusion. An increase in reticulated platelets
      demonstrates impending platelet recovery. A new rapid automated method to assess
      reticulated platelets, the immature platelet fraction (IPF), is described, and
      its clinical utility assessed. The IPF is identified by flow cytometry with the
      use of a nucleic acid specific dye in the reticulocyte channel on the Sysmex XE
      2100. Fifty healthy adult volunteers were used to establish the normal range.
      Patients where platelet marrow production or destruction might be abnormal were
      studied, and some patients followed serially during treatment. Thirty patients
      receiving cytotoxic chemotherapy were tested, and 13 of these patients followed
      serially. Fifteen patients post-autologous or allogeneic transplant were followed
      daily for platelet count and IPF percentage to monitor platelet recovery. The
      method demonstrates good reproducibility and stability. The recovery phase of
      thrombocytopenia in most chemotherapy and transplant patients was preceded by a
      rise in IPF percentage several days prior to platelet recovery. In particular,
      patients undergoing autologous transplantation (n = 8) using peripherally
      collected stem cells have a characteristic IPF percentage motif, with a rise one
      or two days prior to engraftment. The automated IPF is a useful parameter in the
      clinical evaluation of the thrombocytopenic patient and has the potential to
      allow optimal transfusion of platelet concentrates.

PMID- 16623917
TI  - Simultaneous five cell-lineage flow cytometric analysis system for detection of
      leucocyte antibodies.
AB  - Although flow cytometric (FCM) analysis is one of the most widely used approaches
      to screen the presence of leucocyte antibodies, it has several drawbacks. First,
      neutrophils and, especially, monocytes exhibit high background reactivity.
      Second, to determine antibody specificity, it is often necessary to examine not
      only neutrophils and monocytes but also other lineage cells including T cells, B
      cells and platelets. Therefore, we attempted to establish an FCM analysis system
      in which four lineages of leucocytes and platelets are simultaneously tested with
      low background. FCM analysis was performed using ethylene diamine tetraacetic
      acid-anticoagulated whole blood as cell sample without any cell preparation.
      Discrimination of five cell lineages was carried out based on the differences in
      forward vs. side scatter distribution and in the expression of CD4, CD20 and
      CD14. When anti-HNA (human neutrophil antigen) 1b antiserum was applied to HNA 1b
      positive blood samples, only neutrophils were unambiguously positive. When anti
      Naka (anti-CD36) antiserum was applied, only platelets and monocytes were
      positive. The background reactivity of neutrophils and monocytes was low enough.
      When anti-human leucocyte antigen (HLA) class II antiserum was tested, only B
      lymphocytes and monocytes were positive. When anti-HLA class I antiserum was
      tested, all the five-lineage cells were positive.

PMID- 16623918
TI  - Development of non-agglutination microarray blood grouping.
AB  - Microarray technology provides an opportunity to monitor multiple parameters
      simultaneously. High-throughput applications such as blood donation screening
      could greatly benefit from performing various tests on a single testing platform.
      Blood grouping represents one part of the donation testing complementing the
      screening for blood-borne pathogens. Blood group serology traditionally exploited
      agglutination as the detection method. In this investigation, we have adapted
      blood grouping reactions to a solid-phase microarray substrate in a non
      agglutination reaction format as an initial step in the development of a combined
      microarray testing platform. We have investigated immobilization of proprietary
      antibodies on multiple surfaces and monitored their performance under various
      reaction conditions. For the first time, highly specific blood grouping has been
      achieved on a planar microarray using directly labelled erythrocytes or a
      secondary labelled reagent using fluorescent signal end point readout. We have
      also complemented microarray data with a label-free, surface plasmon resonance
      based Biacore platform data and used the real time quantitative measurement to
      rank anti-A antibodies according to the strength of reaction with the immobilized
      synthetic blood group antigen A.

PMID- 16623919
TI  - Comparison of three microtube column agglutination systems for antibody
      screening: DG Gel, DiaMed-ID and Ortho BioVue.
AB  - The aims of the present study were to evaluate the estimated diagnostic accuracy
      of a new microtube column agglutination system (DG Gel, Diagnostic Grifols,
      Barcelona, Spain), to analyse the antibody reactivity and to compare the data
      with the two well-established DiaMed-ID and Ortho BioVue systems. We collected
      3024 consecutive samples from blood donors, transfusion recipients and pregnant
      women, and 100 samples containing antibodies of known specificity. All these
      samples were tested in parallel by the three microtube agglutination systems. The
      estimated sensitivity was 100% for DG Gel and Ortho BioVue and 97.58% for DiaMed
      ID. The estimated specificity was 99.93% for Ortho BioVue and 100% for DiaMed-ID
      and DG Gel. The score mean and range of the antibody titration of DG Gel, DiaMed
      ID and Ortho BioVue were 34.31 (5-119), 30.3 (3-121) and 37.38 (3-112),
      respectively. All three column agglutination systems work well showing a high
      estimated diagnostic accuracy.

PMID- 16623920
TI  - Role of parenteral iron in transfusion requirements after total hip replacement.
      A pilot study.
AB  - An important percentage of patients undergoing total hip replacement (THR)
      receive allogeneic blood transfusion (ABT) to avoid the risks of acute anaemia.
      However, concerns about the risks of ABT have led to the search for alternatives,
      such as stimulation of erythropoiesis. We prospectively investigated the effect
      of postoperative administration of 300 mg of intravenous iron sucrose on ABT
      requirements in THR patients (group 2; n = 24). A previous series of 22 THR
      patients served as the control group (group 1). All patients were operated on by
      the same surgeon, using the same implant, and a set of clinical data was
      gathered. No adverse reactions to iron administration were observed. The group
      given iron showed a trend to a lower transfusion rate (46 vs. 73%; P = 0.067) and
      lower transfusion index (0.96 vs. 1.68 units/patient; P = 0.038). Moreover,
      amongst the non-transfused patients, admission haemoglobin levels were lower in
      those coming from the iron group than those from the control group (12.7 +/- 0.9
      vs. 14.0 +/- 1.2 g dL(-1), respectively; P = 0.017). Postoperative parenteral
      iron administration could be a safe and effective way to reduce ABT requirements
      in the THR patients. A large, randomized controlled trial to confirm these
      results is warranted.

PMID- 16623921
TI  - Neonatal alloimmune thrombocytopenia caused by human leucocyte antigen-B27
      antibody.
AB  - Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies
      to antigens presented on foetal platelets cause their immune destruction. Whether
      human leucocyte antigen (HLA) antibodies can cause NAIT is controversial. Here, a
      patient was described who suffered from a NAIT caused by an HLA-B27 antibody.
      Sera from the mother and the newborn were tested for human platelet antigen
      antibodies and HLA antibodies by monoclonal antibody-specific immobilization of
      platelet antigens (MAIPA) assay, solid phase-linked immunosorbent assay (ELISA),
      lymphocytotoxicity assay (LCT) and flow cytometric analysis. No antibodies
      against cluster designation (CD)109 and platelet glycoproteins of the father were
      found in patient's and mother's serum. However, HLA ELISA was used to identify
      HLA antibody in both sera. The antibody was specified as HLA-B27 antibody. Typing
      results showed that the father descended HLA-B27 antigen on patient and his
      brother. The mother was HLA-B27 negative. It is most conceivable that the
      previous pregnancy of the mother induced the production of anti-HLA-B27 antibody,
      which crossed the placenta and subsequently caused an NAIT in the case presented.

PMID- 16623922
TI  - Regarding the article "costs associated with blood transfusion in Sweden - the
      societal cost of autologous, allogeneic and perioperative RBC transfusion".

PMID- 16623924
TI  - Time, space and contextual models of the immunity tolerance decision: bridging
      the geographical divide of Zinkernagel and Hengartner's 'Credo 2004'.
AB  - In Credo 2004, Zinkernagel and Hengartner (Z&H) have continued their challenge to
      the immunological community to reconsider assumptions regarding the most
      fundamental aspects of adaptive immunity. They have appropriately championed the
      role of persistent, widely distributed antigen in tolerance induction, parameters
      that do not figure prominently in most other models. The global theory of
      immunity they have developed is predominantly based on observations from studies
      with viruses and tumours. I suggest here that a more successful approach to
      generating a theory of the default rules of immunity can be obtained through the
      study of immunity versus tolerance in the setting of transplantation.
      Transplantation studies lack the confounding variable of competing evolution
      present in responses to specific infectious agents and tumours and, therefore,
      more clearly elucidate default rules of immunity. The geographical model in Credo
      2004, primarily a one-signal model regulated by antigen, is contrasted with (1)
      Cohn's time-based two-signal model and (2) a development-context model that
      postulates distinct central and peripheral tolerance mechanisms.

PMID- 16623925
TI  - Human cell lines used in a micro neutralization test for measuring influenza
      neutralizing antibodies.
AB  - An in situ neutralization test (NT) including ELISA for the measurement of
      influenza antigen was developed and evaluated. Two human cell lines, fibroblasts
      (HS27) cells and salivary gland epithelial duct (HSG) cells, were compared with
      Madin-Darby Canine Kidney (MDCK) cells. The viral production in the human cell
      lines was lower than that for MDCK cells, which influenced the results of the
      assay in the HSG and HS27 cells. However, when lowering the infectious dose, the
      NT using HS27 cells gave a sensitive and stable assay with low background in the
      ELISA. The NT titres were very low when using HSG cells compared to MDCK cells.
      The HS27 NT was used to analyze the humoral response after an influenza A
      infection in patients from a placebo-controlled zanamivir study. We found no
      differences in NT titres between patients treated with zanamivir or placebo. The
      MDCK and HS27 NT gave higher titres and more pronounced titre differences than
      the gold standard haemagglutinin inhibition (HAI) assay. Compared to the HAI
      assay, the sensitive NT using HS27 cells also revealed heterologous NT-titre
      rises after influenza infection in the patients.

PMID- 16623926
TI  - In vitro-generated viral double-stranded RNA in contrast to
      polyinosinic:polycytidylic acid induces interferon-alpha in human plasmacytoid
      dendritic cells.
AB  - Double-stranded RNA (dsRNA) arises in the cytoplasm during viral replication and
      was shown to participate in the interferon (IFN)-alpha induction process. Besides
      the intracellular recognition, released dsRNA from dying, infected cells can
      function as a pathogen-associated molecular pattern (PAMP) for the innate immune
      system. In the present study, in vitro-generated dsRNA fragments of genomic
      sequences of Newcastle disease virus were used to induce IFN-alpha release in
      human peripheral blood mononuclear cells (PBMC), in immature myeloid dendritic
      cells (mDC) and in immature plasmacytoid DC (pDC). The extracellular
      administration of dsRNA fragments but not the application of the corresponding
      single-stranded RNA (ssRNA) strands led to an IFN-alpha production in PBMC. The
      synthetic dsRNA analogue polyinosinic acid : polycytidylic acid [Poly(I : C)]
      could only stimulate IFN-alpha production in enriched mDC but not in pDC. In
      contrast, dsRNA fragments induced IFN-alpha only in pDC. Complexation of dsRNA
      fragments with transfection reagents increased the efficiency of IFN-alpha
      induction and commuted ssRNA molecules into IFN-alpha inducers. However,
      stimulation of in vitro-generated murine Toll-like receptor 7 (TLR7) knockout DC
      and human TLR-transfected HEK293 cells with dsRNA fragments gave no evidences for
      the involvement of pDC-specific TLR7 or TLR9 in the observed IFN-alpha induction.

PMID- 16623927
TI  - Transient appearance of hepatic natural killer cells with high cytotoxicity and
      unique phenotype in very young mice.
AB  - There were few natural killer (NK) cells in the liver in very young mice at the
      age of 1-2 weeks. This was because the cell yield from the liver of young mice
      was low. The percentage of NK cells in the liver of young mice, however, was
      almost comparable with that in the liver of adult mice. Lymphocytes were isolated
      from the liver and spleen of C57BL/6 (B6) mice, and NK cytotoxicity and phenotype
      were herein examined in this study. NK cytotoxicity was extremely high in the
      liver of very young mice. This phenomenon was seen in the liver of various normal
      mouse strains. In contrast, the appearance of high cytotoxicity was not seen in
      NK cells of the spleen, irrespective of mouse strains. The quality of NK cells in
      the liver of young mice was different from that in adult mice. NK cells in the
      liver of young mice were mainly CD69(+)Mac-1(-) Fas ligand(+), whereas those in
      the liver of adult mice were CD69(-)Mac-1(+) Fas ligand(-). These results
      revealed that the quality of hepatic NK cells changes in the process of ageing.
      Namely, liver NK cells in very young mice temporarily show the highest NK
      cytotoxicity and a unique activated phenotype. Physiological meaning of the
      present phenomenon was discussed.

PMID- 16623928
TI  - FcgammaRIII-expressing macrophages are essential for development of collagen
      induced arthritis.
AB  - IgG-binding Fc receptors, and in particular FcgammaRIII, are crucial for
      induction of collagen-induced arthritis (CIA), as FcgammaRIII-deficient mice are
      highly protected to arthritis. However, which of the FcgammaRIII-expressing cells
      that is responsible for induction of arthritis is not known. In this study, we
      have addressed this question by purifying different FcgammaRIII(+) cell
      populations, transferred them to FcgammaRIII-deficient mice and studied if the
      recipient mice can develop arthritis. The cell populations were isolated from
      spleen, bone marrow and the peritoneal cavity. Our results show that
      FcgammaRIII(+) CD11b(+) peritoneal macrophages can render FcgammaRIII-deficient
      mice susceptible to CIA. In contrast, FcgammaRIII(-) peritoneal macrophages or
      FcgammaRIII(+) spleenocytes, bone marrow cells, mast cells or monocytes could not
      mediate this effect. To further evaluate the contribution of the FcgammaRIII(+)
      macrophages in arthritis, we investigated the cytokine profile in these cells
      during CIA. The arthritic macrophages exhibited significantly higher mRNA levels
      of TNFalpha and IL-12p35 compared with macrophages from normal mice. We conclude
      that FcgammaRIII-expressing macrophages, producing pro-inflammatory cytokine and
      T helper type 1 differentiating factor, are the major effector cells in the
      induction of CIA.

PMID- 16623929
TI  - Role of very late antigen-1 in T-cell-mediated immunity to systemic viral
      infection.
AB  - The T-cell response to lymphocytic choriomeningitis virus was studied in mice
      lacking very late antigen-1 (VLA-1). The generation of virus-specific effector T
      cells was unimpaired in VLA-1(-/-) mice. In the memory phase, VLA-1 deficiency
      did not influence the number of memory CD8(+) T cells or their distribution
      between lymphoid and nonlymphoid organs. Regarding a functional role of VLA-1, we
      found that intracerebral infection of both VLA-1(-/-) and wild-type (wt) mice
      resulted in lethal T-cell-mediated meningitis, and quantitative and qualitative
      analyses of the cellular exudate did not reveal any significant differences
      between the two strains. Expression of VLA-1 was also found to be redundant
      regarding the ability of effector T cells to eliminate virus from internal organs
      of i.v. infected mice. Using delayed-type hypersensitivity (DTH) assays to
      evaluate subdermal CD8(+) T-cell-mediated inflammation, no significant influence
      of VLA-1 was found either in the primary response or in the memory phase.
      However, alpha-VLA-4 antibody reduced the DTH-like reaction in VLA-1(-/-) mice to
      a higher degree than in wt mice, suggesting a synergistic effect of blocking both
      integrins. Taken together, the current findings indicate that the expression of
      VLA-1 is not pivotal for T-cell-mediated antiviral immunity to a systemic
      infection.

PMID- 16623930
TI  - The reduction of serum B-lymphocyte activating factor levels following quinacrine
      add-on therapy in systemic lupus erythematosus.
AB  - B-Lymphocyte-activating factor (BAFF/BLyS) is a survival factor for B cells,
      belonging to the tumor necrosis ligand super family. Serum BAFF levels have been
      found to be elevated in patients with systemic lupus erythematosus (SLE).
      Neutralization of BAFF activity was suggested as an additional therapeutic
      approach in SLE. To determine the effect of add-on Quinacrine (Qn) treatment on
      serum BAFF levels and the effect of this treatment on SLE disease activity index
      (SLEDAI), antidsDNA and anticardiolipin (aCL) antibody levels, we treated 29
      stable SLE patients, who were maintained on prednisolone and hydroxychloroquine
      and in some on azathioprine (AZT), with additional Qn (100 mg/d) with an aim to
      further reduce disease activity. SLEDAI, antidsDNA, aCL antibodies and serum BAFF
      levels were assessed before and 3 months after the addition of Qn. Three months
      following Qn initiation, a reduction in SLEDAI was noticed in 19/29 patients
      (mean 8.8 +/- 2.3 to 3.3 +/- 1.5, P = 0.009), followed by reduction or
      discontinuation of prednisolone in all patients and the discontinuation of AZT in
      five patients. Serum BAFF levels were significantly reduced in 8/12 patients
      (mean 6.3 +/- 0.5 to 3.0 +/- 0.56 ng/ml P = 0.0001). This reduction was found in
      correlation with a decrease in aCL titres. However, the decrease in SLEDAI scores
      and antidsDNA antibody titres was unrelated to the decrease in serum BAFF or aCL
      levels. We conclude that the addition of Qn to previous therapeutic regimens in
      active SLE is beneficial and seems to reduce SLEDAI scores, serum BAFF and aCL
      levels and therefore should be considered in many of our SLE patients before
      aggressive treatments are given.

PMID- 16623931
TI  - High-altitude climate therapy reduces local airway inflammation and modulates
      lymphocyte activation.
AB  - High-altitude climate therapy is a well-established therapeutic option, which
      improves clinical symptoms in asthma. However, little is known about the
      underlying immunological mechanisms. The study investigates the influence of high
      altitude climate therapy on airway inflammation and cellular components of
      specific and unspecific immune response. Exhaled NO significantly decreased
      within 3 weeks of therapy in patients with allergic and intrinsic, moderate and
      severe asthma. Interleukin-10 (IL-10)-secreting peripheral blood mononuclear
      cells (PBMC) increased within 3 weeks of therapy in six of 11 patients, whereas
      transforming growth factor-beta(1)-secreting PBMC remained stable. Furthermore,
      monocyte activation, assessed by CD80 expression significantly decreased during
      therapy. The frequency of CRTH2-expressing T cells decreased, while regulatory T
      cells (T(reg)) remained stable. FOXP3 and GATA-3 mRNA expression in CD4(+) T
      cells did not change, while interferon-gamma and IL-13 mRNA expression decreased
      in eight of 10 patients. The current data demonstrate that high-altitude climate
      therapy reduces local airway inflammation. Furthermore, monocytes switch towards
      a tolerogenic phenotype under high-altitude climate therapy. The T(reg)/Th2 ratio
      increases; however, because of the absence of antigens/allergens, no de novo
      differentiation of Th2 nor T(reg) cells is observed. The high-altitude climate
      therapy therefore may form the immunological basis for the endogenous control of
      allergen-driven diseases.

PMID- 16623932
TI  - Significance of alterations in PBMC immunophenotype of children with chronic
      viral hepatitis C-- the role of dendritic cells.
AB  - There are differences in the clinical course of chronic viral hepatitis C between
      adults and children, but it is generally accepted that the disease has cell
      mediated immune background. The aim of this study was to evaluate PBMC subsets in
      children with chronic hepatitis C before treatment in order to find some
      predictive factors, useful for patients management. Several PBMC subsets, in
      particular lymphoid and dendritic cell (DC) ones, were tested by flow cytometry
      in HCV(+) paediatric patients (n = 46) and in control children matched in terms
      of age and sex (n = 20). Data were subjected to extensive statistics. It was
      found that cells with cytotoxic potential such as CD8(+)CD28(-) T cells, NK and
      NKT cells as well as lineage(-)HLA-DR(+) DC were increased in per cent values,
      while CD4(+) T cells and CD4:CD8 ratio were decreased in hepatitis C group. In
      HCV(+) patients, CD4(+) T cells were inversely correlated with alanine
      aminotransferase (ALT) levels and with viraemia. DC subset of myeloid origin
      (CD11c(+)) assessed both in per cent values and as mean fluorescence intensity
      (MFI) of HLA-DR expression was shown to be downregulated in hepatitis patients,
      in spite of increased numbers. To conclude, PBMC subsets, and in particular DC,
      are affected by HCV chronic infection in children, reflected by the correlation
      with clinical parameters, such as ALT and viraemia.

PMID- 16623933
TI  - Effect of N-arachidonoyl-(2-methyl-4-hydroxyphenyl) amine (VDM11), an anandamide
      transporter inhibitor, on capsaicin-induced cough in mice.
AB  - BACKGROUND: Several observations have suggested that anandamide, an endogenous
      cannabinoid ligand, plays an important role in the modulation of cough
      sensitivity. However, it is unknown whether the anandamide membrane transporter
      plays a role in this modulation. To test this hypothesis, we investigated the
      effects of VDM11, an anandamide membrane transporter inhibitor, on capsaicin- and
      anandamide-induced cough. METHODS: The effect of VDM11, an anandamide membrane
      transporter inhibitor, on capsaicin- and anandamide-induced cough in mice was
      examined. RESULTS: VDM11, at doses of 3-10 mg/kg subcutaneously, produced a dose
      dependent antitussive effect. This antitussive effect was antagonized by
      pretreatment with either intraperitoneal administration (3 mg/kg) or inhalation
      (1 mg/ml) of SR141716A, a cannabinoid receptor (CB1) antagonist. However,
      intracerebroventricular injection of SR141716A (0.03 mg/mouse) did not alter the
      effect of VDM11. Exposure of mice to a nebulized solution of 10% DMSO, a vehicle
      of anandamide, induced a cough response (7.7 +/- 0.6 coughs/3 min; n = 10).
      Exposure of mice to a nebulized solution of anandamide, at concentrations of
      0.03, 0.3 and 3 mg/ml, also produced a cough response in a concentration
      dependent manner. The number of coughs induced by low dose (0.03 mg/ml)
      anandamide was significantly less than that of 10% DMSO. On the other hand, the
      number of coughs induced by high dose (3 mg/ml) anandamide was significantly
      greater than that of 10% DMSO. When AM251 (1.8 mM), a selective CB1 receptor
      antagonist, was given by aerosol for 4 min before inhalation of 0.03 mg/ml of
      anandamide, the number of coughs was significantly increased to the level
      observed with 10% DMSO alone. When capsazepine (0.3 mM), a selective TRPV1
      receptor antagonist, was given via aerosol for 4 min before inhalation of 3 mg/ml
      of anandamide, the number of coughs was significantly decreased to the levels
      observed with 10% DMSO alone. The number of coughs induced by high dose (3 mg/ml)
      anandamide was significantly and dose-dependently reduced by the pretreatment
      with VDM11. CONCLUSION: These results suggest that anandamide, an endogenous
      cannabinoid ligand, may modulate cough sensitivity and that anandamide
      transporters play an important role in this modulation. Furthermore, these
      findings indicate that inhibition of the uptake of anandamide produced a potent
      antitussive effect and suggests that the anandamide transporter may be a
      potential target for peripherally acting antitussive drugs.

PMID- 16623934
TI  - Comparative effectiveness of manipulation, mobilisation and the activator
      instrument in treatment of non-specific neck pain: a systematic review.
AB  - BACKGROUND: Neck pain is a common problem and different forms of manual therapy
      are used in its treatment. The purpose of this systematic review was to
      critically appraise the literature that directly compared manipulation,
      mobilisation and the Activator instrument for non-specific neck pain. METHODS:
      Electronic databases (MEDLINE, MANTIS and CINAHL) were searched from their
      inception to October 2005 for all English language randomised clinical trials
      that directly compared manipulation, mobilisation and the Activator instrument.
      Inclusion and exclusion criteria were applied to select the studies and these
      studies were then evaluated using validated criteria. RESULTS: Five such studies
      were identified. The methodological quality was mostly poor. Findings from the
      studies were mixed and no one therapy was shown to be more effective than the
      others. CONCLUSION: Further high quality research has to be done before a
      recommendation can be made as to the most effective manual method for non
      specific neck pain.

PMID- 16623935
TI  - A methodology for assessing the professional development needs of nurses and
      midwives in Indonesia: paper 1 of 3.
AB  - BACKGROUND: Despite recent developments, health care provision in Indonesia
      remains suboptimal. Difficult terrain, economic crises, endemic diseases and high
      population numbers, coupled with limited availability of qualified health care
      professionals, all contribute to poor health status. In a country with a
      population of 220 million, there are currently an estimated 50 nurses and 26
      midwives per 100,000 people. In line with government initiatives, this series of
      studies was undertaken to establish the training and development needs of nurses
      and midwives working within a variety of contexts in Indonesia, with the ultimate
      aim of enhancing care provision within these domains. METHODS: An established,
      psychometrically valid and reliable training needs instrument was modified for
      use within the Indonesian context. While this technique has had widespread
      international use in the developed world, its application for developing
      countries has not yet been established. The standard form consists of a
      biographical cover sheet and a core set of 30 items (all health-related tasks),
      which have to be rated along two seven-point scales. The first of these scales
      asks respondents to assess how important the task is to their job and the second
      scale is a self-assessment of respondents' current performance level of the task.
      By comparing the importance rating with the performance rating, an index of
      training need can be obtained (high importance and low performance indicating a
      significant training need). The modifications incorporated for use in this series
      of studies were a further 10 items, which were constructed following expert group
      and focus group discussions and a review of the relevant literature. Pilot trials
      with 109 respondents confirmed its feasibility and acceptability. The instrument
      was then administered to 524 nurses and 332 midwives across Indonesia. RESULTS:
      The data were subjected to a retrospective factor analysis, using a Varimax
      rotation and Cronbach's alpha to check the instrument's validity and reliability
      following modification. The results yielded six factors, which accounted for >53%
      of the variance, each of which had a Cronbach's alpha score of between 0.8644 and
      0.7068. CONCLUSION: The results suggest that the modified instrument remained
      valid and reliable for use in the Indonesian nursing and midwifery context.

PMID- 16623936
TI  - An integrated system for genetic analysis.
AB  - BACKGROUND: Large-scale genetic mapping projects require data management systems
      that can handle complex phenotypes and detect and correct high-throughput
      genotyping errors, yet are easy to use. DESCRIPTION: We have developed an
      Integrated Genotyping System (IGS) to meet this need. IGS securely stores, edits
      and analyses genotype and phenotype data. It stores information about DNA
      samples, plates, primers, markers and genotypes generated by a genotyping
      laboratory. Data are structured so that statistical genetic analysis of both case
      control and pedigree data is straightforward. CONCLUSION: IGS can model complex
      phenotypes and contain genotypes from whole genome association studies. The
      database makes it possible to integrate genetic analysis with data curation. The
      IGS web site http://bioinformatics.well.ox.ac.uk/project-igs.shtml contains
      further information.

PMID- 16623937
TI  - A clinical genetic method to identify mechanisms by which pain causes depression
      and anxiety.
AB  - BACKGROUND: Pain patients are often depressed and anxious, and benefit less from
      psychotropic drugs than pain-free patients. We hypothesize that this partial
      resistance is due to the unique neurochemical contribution to mood by afferent
      pain projections through the spino-parabrachial-hypothalamic-amygdalar systems
      and their projections to other mood-mediating systems. New psychotropic drugs for
      pain patients might target molecules in such brain systems. We propose a method
      to prioritize molecular targets by studying polymorphic genes in cohorts of
      patients undergoing surgical procedures associated with a variable pain relief
      response. We seek molecules that show a significant statistical interaction
      between (1) the amount of surgical pain relief, and (2) the alleles of the gene,
      on depression and anxiety during the first postoperative year. RESULTS: We
      collected DNA from 280 patients with sciatica due to a lumbar disc herniation,
      162 treated surgically and 118 non-surgically, who had been followed for 10 years
      in the Maine Lumbar Spine Study, a large, prospective, observational study. In
      patients whose pain was reduced >25% by surgery, symptoms of depression and
      anxiety, assessed with the SF-36 Mental Health Scale, improved briskly at the
      first postoperative measurement. In patients with little or no surgical pain
      reduction, mood scores stayed about the same on average. There was large inter
      individual variability at each level of residual pain. Polymorphisms in three pre
      specified pain-mood candidate genes, catechol-O-methyl transferase (COMT),
      serotonin transporter, and brain-derived neurotrophic factor (BDNF) were not
      associated with late postoperative mood or with a pain-gene interaction on mood.
      Although the sample size did not provide enough power to persuasively search
      through a larger number of genes, an exploratory survey of 25 other genes
      provides illustrations of pain-gene interactions on postoperative mood--the mu
      opioid receptor for short-term effects of acute sciatica on mood, and the galanin
      2 receptor for effects of unrelieved post-discectomy pain on mood one year after
      surgery. CONCLUSION: Genomic analysis of longitudinal studies of pain,
      depression, and anxiety in patients undergoing pain-relieving surgery may help to
      identify molecules through which pain alters mood. Detection of alleles with
      modest-sized effects will require larger cohorts.

PMID- 16623938
TI  - Subclinical thyroid disorders and cognitive performance among adolescents in the
      United States.
AB  - BACKGROUND: Thyroid hormone plays a crucial role in the growth and function of
      the central nervous system. The purpose of the study was to examine the
      relationships between the status of subclinical thyroid conditions and cognition
      among adolescents in the United States. METHODS: Study sample included 1,327
      adolescents 13 to 16 years old who participated in the Third National Health and
      Nutrition Examination Survey (NHANES III). Serum thyroxine (T4) and thyroid
      stimulating hormone (TSH) were measured and subclinical hypothyroidism,
      subclinical hyperthyroidism, and euthyroid groups were defined. Cognitive
      performance was assessed using the subscales of the Wide Range Achievement Test
      Revised (WRAT-R) and the Wechsler Intelligence Scale for Children-Revised (WISC
      R). The age-corrected scaled scores for arithmetic, reading, block design, and
      digit span were derived from the cognitive assessments. RESULTS: Subclinical
      hypothyroidism was found in 1.7% and subclinical hyperthyroidism was found in
      2.3% of the adolescents. Cognitive assessment scores on average tended to be
      lower in adolescents with subclinical hyperthyroidism and higher in those with
      subclinical hypothyroidism than the score for the euthyroid group. Adolescents
      with subclinical hypothyroidism had significantly better scores in block design
      and reading than the euthyroid subjects even after adjustment for a number of
      variables including sex, age, and family income level. CONCLUSION: Subclinical
      hypothyroidism was associated with better performance in some areas of cognitive
      functions while subclinical hyperthyroidism could be a potential risk factor.

PMID- 16623939
TI  - Case report and summary of literature: giant perineal keloids treated with post
      excisional radiotherapy.
AB  - BACKGROUND: Keloids are common benign tumors of the dermis, typically arising
      after insult to the skin. While typically only impinging on cosmesis, large or
      recurrent keloids may require therapeutic intervention. While no single
      standardized treatment course has been established, several series report
      excellent outcomes for keloids with post-surgery radiation therapy. CASE
      PRESENTATION: We present a patient with a history of recurrent keloids arising in
      the absence of an ascribed trauma and a maternal familial history of keloid
      formation, whose physical examination several large perineal keloids of 6-20 cm
      in the largest dimension. The patient was treated with surgical extirpation and
      adjuvant radiation therapy. Radiotherapy was delivered to the scar bed to a total
      dose of 22 Gy over 11 daily fractions. Acute radiotherapy toxicity necessitated a
      treatment break due to RTOG Grade III acute toxicity (moderate ulceration and
      skin breakdown) which resolved rapidly during a 3-day treatment break. The
      patient demonstrated local control and has remained free of local recurrence for
      more than 2 years. CONCLUSION: Radiotherapy for keloids represents a safe and
      effective option for post-surgical keloid therapy, especially for patients with
      bulky or recurrent disease.

PMID- 16623941
TI  - Analgesia for labour pain--analysis of the trends and associations in the
      Grampian region of Scotland between 1986 and 2001.
AB  - BACKGROUND: Although intrapartum analgesia has been in use since Victorian times,
      there have been few attempts to study its usage from routinely collected data.
      This population based epidemiological study aimed to analyse retrospective data
      on the distribution of different types of labour analgesia used by women in the
      Grampian region of Scotland between 1986 and 2001 in order to examine time trends
      and associations. METHODS: Data records on all deliveries occurring in the years
      1986 to 2001 were extracted from the Aberdeen Maternity and Neonatal Databank.
      The rates of the use of epidural, opioid and Entonox or no analgesia for pain
      relief in labour in each year were calculated. Maternal, pregnancy, labour and
      delivery characteristics were compared among the users of three different
      analgesics by univariate and multivariate analyses. RESULTS: A total of 81,418
      deliveries were analysed. Of these, 12,659 (15.5%) women had epidural, 33,819
      (41.5%) had used opioids and 26,974(33.1%) received either Entonox or no
      analgesia at all. The women who received epidural analgesia were younger, shorter
      and heavier and had larger babies (OR = 1.05, 95% CI 1.01, 1.08). Three quarters
      of them were primigravidae and had longer periods of gestation. They were also
      more likely to have suffered pregnancy related complications (OR = 2.11, 95% CI
      1.8, 2.4). Labour was more likely to have been induced (OR = 2.8, 95% CI 2.6,
      2.9) and to have lasted longer in this group of women. Women in this group were 5
      times more likely to have an instrumental delivery (95% CI 4.9, 5.1) and 7 times
      more likely to have a Caesarean section (95% CI 5.7, 9.3). CONCLUSION: Non
      epidural analgesia was found to be the most popular choice for pain relief in
      labour in the Grampian region between 1986 and 2001, although an increase in the
      uptake of epidural services is starting to occur. The type of labour analgesia
      used is associated with the epidemiological characteristics of the women's
      pregnancy, labour and delivery.

PMID- 16623940
TI  - Assessment of the relationship between pre-chip and post-chip quality measures
      for Affymetrix GeneChip expression data.
AB  - BACKGROUND: Gene expression microarray experiments are expensive to conduct and
      guidelines for acceptable quality control at intermediate steps before and after
      the samples are hybridised to chips are vague. We conducted an experiment
      hybridising RNA from human brain to 117 U133A Affymetrix GeneChips and used these
      data to explore the relationship between 4 pre-chip variables and 22 post-chip
      outcomes and quality control measures. RESULTS: We found that the pre-chip
      variables were significantly correlated with each other but that this correlation
      was strongest between measures of RNA quality and cRNA yield. Post-mortem
      interval was negatively correlated with these variables. Four principal
      components, reflecting array outliers, array adjustment, hybridisation noise and
      RNA integrity, explain about 75% of the total post-chip measure variability. Two
      significant canonical correlations existed between the pre-chip and post-chip
      variables, derived from MAS 5.0, dChip and the Bioconductor packages affy and
      affyPLM. The strongest (CANCOR 0.838, p < 0.0001) correlated RNA integrity and
      yield with post chip quality control (QC) measures indexing 3'/5' RNA ratios,
      bias or scaling of the chip and scaling of the variability of the signal across
      the chip. Post-mortem interval was relatively unimportant. We also found that the
      RNA integrity number (RIN) could be moderately well predicted by post-chip
      measures B_ACTIN35, GAPDH35 and SF. CONCLUSION: We have found that the post-chip
      variables having the strongest association with quantities measurable before
      hybridisation are those reflecting RNA integrity. Other aspects of quality, such
      as noise measures (reflecting the execution of the assay) or measures reflecting
      data quality (outlier status and array adjustment variables) are not well
      predicted by the variables we were able to determine ahead of time. There could
      be other variables measurable pre-hybridisation which may be better associated
      with expression data quality measures. Uncovering such connections could create
      savings on costly microarray experiments by eliminating poor samples before
      hybridisation.

PMID- 16623942
TI  - Quality control for terms and definitions in ontologies and taxonomies.
AB  - BACKGROUND: Ontologies and taxonomies are among the most important computational
      resources for molecular biology and bioinformatics. A series of recent papers has
      shown that the Gene Ontology (GO), the most prominent taxonomic resource in these
      fields, is marked by flaws of certain characteristic types, which flow from a
      failure to address basic ontological principles. As yet, no methods have been
      proposed which would allow ontology curators to pinpoint flawed terms or
      definitions in ontologies in a systematic way. RESULTS: We present computational
      methods that automatically identify terms and definitions which are defined in a
      circular or unintelligible way. We further demonstrate the potential of these
      methods by applying them to isolate a subset of 6001 problematic GO terms. By
      automatically aligning GO with other ontologies and taxonomies we were able to
      propose alternative synonyms and definitions for some of these problematic terms.
      This allows us to demonstrate that these other resources do not contain
      definitions superior to those supplied by GO. CONCLUSION: Our methods provide
      reliable indications of the quality of terms and definitions in ontologies and
      taxonomies. Further, they are well suited to assist ontology curators in drawing
      their attention to those terms that are ill-defined. We have further shown the
      limitations of ontology mapping and alignment in assisting ontology curators in
      rectifying problems, thus pointing to the need for manual curation.

PMID- 16623943
TI  - Is Fecal Leukocyte Test a good predictor of Clostridium difficile associated
      diarrhea?
AB  - BACKGROUND: Fecal leukocyte test (FLT) is widely used to screen for invasive
      diarrheas including C. difficile associated diarrhea (CDAD), which account for
      more than 25 % of all antibiotic associated diarrhea. METHOD: 263 stool samples
      from patients with suspected CDAD were studied simultaneously for fecal leukocyte
      test (FLT) and Clostridium difficile toxin assay (CDTA). FLT was performed by the
      Giemsa technique and CDTA was performed by enzyme immuno assay (EIA). RESULTS:
      Sensitivity, specificity, positive predictive value and negative predictive value
      of FLT as compared to CDTA were 30%, 74.9%, 13.2% and 89.3% respectively.
      CONCLUSION: Considering the poor sensitivity of FLT, and the comparable cost and
      time of obtaining a CDTA at our institution, we conclude that FLT is not a good
      screening test for CDAD. Possible reasons for FLT being a poor predictor of CDTA
      are discussed.

PMID- 16623944
TI  - Cyanobacteria toxins in the Salton Sea.
AB  - BACKGROUND: The Salton Sea (SS) is the largest inland body of water in
      California: surface area 980 km2, volume 7.3 million acre-feet, 58 km long, 14-22
      km wide, maximum depth 15 m. Located in the southeastern Sonoran desert of
      California, it is 85 m below sea level at its lowest point. It was formed between
      1905 and 1907 from heavy river flows of the Colorado River. Since its formation,
      it has attracted both people and wildlife, including flocks of migratory birds
      that have made the Salton Sea a critical stopover on the Pacific flyway. Over the
      past 15 years wintering populations of eared grebe (Podiceps nigricollis) at the
      Salton Sea, have experienced over 200,000 mortalities. The cause of these large
      die-offs remains unknown. The unique environmental conditions of the Salton Sea,
      including salinities from brackish freshwater at river inlets to hypersaline
      conditions, extreme daily summer temperatures (>38 degrees C), and high nutrient
      loading from rivers and agricultural drainage favor eutrophic conditions that
      encourage algal blooms throughout the year. A significant component of these
      algal blooms are the prokaryotic group - the Cyanophyta or blue-green algae (also
      called Cyanobacteria). Since many Cyanobacteria produce toxins (the cyanotoxins)
      it became important to evaluate their presence and to determine if they are a
      contributing factor in eared-grebe mortalities at the Salton Sea. RESULTS: From
      November 1999 to April 2001, 247 water and sediment samples were received for
      phytoplankton identification and cyanotoxin analyses. Immunoassay (ELISA)
      screening of these samples found that eighty five percent of all water samples
      contained low but detectable levels of the potent cyclic peptide liver toxin
      called microcystins. Isolation and identification of cyanobacteria isolates
      showed that the picoplanktonic Synechococcus and the benthic filamentous
      Oscillatoria were dominant. Both organisms were found to produce microcystins
      dominated by microcystin-LR and YR. A laboratory strain of Synechococcus was
      identified by PCR as being closest to known marine forms of this genus. Analyses
      of affected grebe livers found microcystins at levels that may account for some
      of the acute mortalities. CONCLUSION: The production of microcystins by a marine
      Synechococcus indicates that microcystins may be a more common occurrence in
      marine environments - a finding not recognized before this work. Further research
      should be done to define the distribution of microcystin producing marine
      cyanobacteria and to determine exposure/response effects of microcystins and
      possibly other cyanotoxins in the Salton Sea. Future efforts to reduce avian
      mortalities and remediate the Salton Sea should evaluate vectors by which
      microcystins enter avian species and ways to control and mitigate toxic
      cyanobacteria waterblooms at the Salton Sea.

PMID- 16623945
TI  - Proteomic analysis of acidic chaperones, and stress proteins in extreme halophile
      Halobacterium NRC-1: a comparative proteomic approach to study heat shock
      response.
AB  - BACKGROUND: Halobacterium sp. NRC-1 is an extremely halophilic archaeon and has
      adapted to optimal growth under conditions of extremely high salinity. Its
      proteome is highly acidic with a median pI of 4.9, a unique characteristic which
      helps the organism to adapt high saline environment. In the natural growth
      environment, Halobacterium NRC-1 encounters a number of stressful conditions
      including high temperature and intense solar radiation, oxidative and cold
      stress. Heat shock proteins and chaperones play indispensable roles in an
      organism's survival under many stress conditions. The aim of this study was to
      develop an improved method of 2-D gel electrophoresis with enhanced resolution of
      the acidic proteome, and to identify proteins with diverse cellular functions
      using in-gel digestion and LC-MS/MS and MALDI-TOF approach. RESULTS: A modified 2
      D gel electrophoretic procedure, employing IPG strips in the range of pH 3-6,
      enabled improved separation of acidic proteins relative to previous techniques.
      Combining experimental data from 2-D gel electrophoresis with available genomic
      information, allowed the identification of at least 30 cellular proteins involved
      in many cellular functions: stress response and protein folding (CctB, PpiA,
      DpsA, and MsrA), DNA replication and repair (DNA polymerase A alpha subunit,
      Orc4/CDC6, and UvrC), transcriptional regulation (Trh5 and ElfA), translation
      (ribosomal proteins Rps27ae and Rphs6 of the 30 S ribosomal subunit; Rpl31eand
      Rpl18e of the 50 S ribosomal subunit), transport (YufN), chemotaxis (CheC2), and
      housekeeping (ThiC, ThiD, FumC, ImD2, GapB, TpiA, and PurE). In addition, four
      gene products with undetermined function were also identified: Vng1807H,
      Vng0683C, Vng1300H, and Vng6254. To study the heat shock response of
      Halobacterium NRC-1, growth conditions for heat shock were determined and the
      proteomic profiles under normal (42 degrees C), and heat shock (49 degrees C)
      conditions, were compared. Using a differential proteomic approach in combination
      with available genomic information, bioinformatic analysis revealed five putative
      heat shock proteins that were upregulated in cells subjected to heat stress at 49
      degrees C, namely DnaJ, GrpE, sHsp-1, Hsp-5 and sHsp-2. CONCLUSION: The modified
      2-D gel electrophoresis markedly enhanced the resolution of the extremely acidic
      proteome of Halobacterium NRC-1. Constitutive expression of stress proteins and
      chaperones help the organism to adapt and survive under extreme salinity and
      other stress conditions. The upregulated expression pattern of putative
      chaperones DnaJ, GrpE, sHsp-1, Hsp-5 and sHsp-2 under elevated temperature
      clearly suggests that Halobacterium NRC-1 has a sophisticated defense mechanism
      to survive in extreme environments.

PMID- 16623946
TI  - Using and interpreting cost-effectiveness acceptability curves: an example using
      data from a trial of management strategies for atrial fibrillation.
AB  - BACKGROUND: The cost-effectiveness acceptability curve (CEAC) is a method for
      summarizing the uncertainty in estimates of cost-effectiveness. The CEAC, derived
      from the joint distribution of costs and effects, illustrates the (Bayesian)
      probability that the data are consistent with a true cost-effectiveness ratio
      falling below a specified ceiling ratio. The objective of the paper is to
      illustrate how to construct and interpret a CEAC. METHODS: A retrospective cost
      effectiveness analysis of the Atrial Fibrillation Follow-up Investigation of
      Rhythm Management (AFFIRM) randomized controlled trial with 4060 patients
      followed for 3.5 years. The target population was patients with atrial
      fibrillation who were 65 years of age or had other risk factors for stroke or
      death similar to those enrolled in AFFIRM. The intervention involved the
      management of patients with atrial fibrillation with antiarrhythmic drugs (rhythm
      control) compared with drugs that control heart rate (rate-control). Measurements
      of mean survival, mean costs and incremental cost-effectiveness were made. The
      uncertainty surrounding the estimates of cost-effectiveness was illustrated
      through a cost-effectiveness acceptability curve. RESULTS: The base case point
      estimate for the difference in effects and costs between rate and rhythm-control
      is 0.08 years (95% CI: -0.1 years to 0.24 years) and -5,077 US dollars (95% CI: 
      1,100 dollars to -11,006 dollars). The CEAC shows that the decision uncertainty
      surrounding the adoption of rate-control strategies is less than 1.7% regardless
      of the maximum acceptable ceiling ratio. Thus, there is very little uncertainty
      surrounding the decision to adopt rate-control compared to rhythm-control for
      patients with atrial fibrillation from a resource point of view. CONCLUSION: The
      CEAC is straightforward to calculate, construct and interpret. The CEAC is useful
      to a decision maker faced with the choice of whether or not to adopt a technology
      because it provides a measure of the decision uncertainty surrounding the choice.

PMID- 16623947
TI  - A role for CETP TaqIB polymorphism in determining susceptibility to atrial
      fibrillation: a nested case control study.
AB  - BACKGROUND: Studies investigating the genetic and environmental characteristics
      of atrial fibrillation (AF) may provide new insights in the complex development
      of AF. We aimed to investigate the association between several environmental
      factors and loci of candidate genes, which might be related to the presence of
      AF. METHODS: A nested case-control study within the PREVEND cohort was conducted.
      Standard 12 lead electrocardiograms were recorded and AF was defined according to
      Minnesota codes. For every case, an age and gender matched control was selected
      from the same population (n = 194). In addition to logistic regression analyses,
      the multifactor-dimensionality reduction (MDR) method and interaction entropy
      graphs were used for the evaluation of gene-gene and gene-environment
      interactions. Polymorphisms in genes from the Renin-angiotensin, Bradykinin and
      CETP systems were included. RESULTS: Subjects with AF had a higher prevalence of
      electrocardiographic left ventricular hypertrophy, ischemic heart disease,
      hypertension, renal dysfunction, elevated levels of C-reactive protein (CRP) and
      increased urinary albumin excretion as compared to controls. The polymorphisms of
      the Renin-angiotensin system and Bradykinin gene did not show a significant
      association with AF (p > 0.05). The TaqIB polymorphism of the CETP gene was
      significantly associated with the presence of AF (p < 0.05). Using the MDR
      method, the best genotype-phenotype models included the combination of micro- or
      macroalbuminuria and CETP TaqIB polymorphism, CRP >3 mg/L and CETP TaqIB
      polymorphism, renal dysfunction and the CETP TaqIB polymorphism, and ischemic
      heart disease and CETP TaqIB polymorphism (1000 fold permutation testing, P <
      0.05). Interaction entropy graph showed that the combination of albuminuria and
      CETP TaqIB polymorphism removed the most entropy. CONCLUSION: CETP TaqIB
      polymorphism is significantly associated with the presence of AF in the context
      of micro- or macroalbuminuria, elevated C-reactive protein, renal dysfunction,
      and ischemic heart disease.

PMID- 16623948
TI  - A retrospective study of cochlear implant outcomes in children with residual
      hearing.
AB  - BACKGROUND: There has been increasing demand for the cochlear implantation of
      children who demonstrate some auditory capacity with conventional hearing aids.
      The purpose of this study was to examine speech recognition outcomes in a group
      of children who were regarded as borderline candidates for cochlear implantation
      as their residual hearing and/or auditory functioning levels exceeded typical
      audiologic candidacy criteria. METHODS: A retrospective chart review was
      undertaken at one Canadian cochlear implant centre to identify children implanted
      at age 4 or older with a pure-tone-average of 90 dB or better and speech
      recognition of 30% or greater. Pre-implant and post-implant open-set word and
      sentence test scores were analyzed. RESULTS: Eleven children of 195 paediatric
      cochlear implant recipients met the inclusion criteria for this study. Speech
      recognition results for the 10 English-speaking children indicated significant
      gains in both open-set word and sentence understanding within the first 6 to 12
      months of implant use. Seven of 9 children achieved 80% open-set sentence
      recognition within 12 months post-surgery. CONCLUSION: Children with several
      years of experience using conventional amplification demonstrated rapid progress
      in auditory skills following cochlear implantation. These findings suggest that
      cochlear implantation may be an appropriate intervention for selected children
      with severe hearing losses and/or auditory capacity outside current candidacy
      criteria.

PMID- 16623950
TI  - Fast drying of Fine Needle Aspiration slides using a hand held fan: impact on
      turn around time and staining quality.
AB  - To analyze the impact of using a hand held fan to speed the air-drying process
      during immediate adequacy evaluation of Fine Needle Aspirations. The effect on
      turn around time and staining quality is evaluated. Two mirror image air-dried
      smears for each pass were prepared. One was subjected to a small hand-held fan
      with a fan diameter of 7 cm held an average distance of 3 to 5 cm from the slide.
      The other smear was left to dry without a fan. A total of 93 consecutive pairs
      were evaluated over a 2-month duration. The average time needed for air-drying
      using the fan was 73 seconds (range 10-300 seconds, standard error 6.986), while
      it was 200 seconds (range 15-645 seconds, standard error 17.799) for those
      without fan. This difference was statistically significant (p < 0.001). Smears
      were then evaluated for single cells, cell clusters and background material and
      no appreciable difference in stain quality was noted between the 2 groups. The
      use of a small hand-held fan for air-drying shortened the drying time for FNA
      adequacy by an average of 127 seconds (63% time reduction) for each pass. The
      quality of staining was comparable. Using a fan is highly recommended.

PMID- 16623949
TI  - Derivation of normal macrophages from human embryonic stem (hES) cells for
      applications in HIV gene therapy.
AB  - BACKGROUND: Many novel studies and therapies are possible with the use of human
      embryonic stem cells (hES cells) and their differentiated cell progeny. The hES
      cell derived CD34 hematopoietic stem cells can be potentially used for many gene
      therapy applications. Here we evaluated the capacity of hES cell derived CD34
      cells to give rise to normal macrophages as a first step towards using these
      cells in viral infection studies and in developing novel stem cell based gene
      therapy strategies for AIDS. RESULTS: Undifferentiated normal and lentiviral
      vector transduced hES cells were cultured on S17 mouse bone marrow stromal cell
      layers to derive CD34 hematopoietic progenitor cells. The differentiated CD34
      cells isolated from cystic bodies were further cultured in cytokine media to
      derive macrophages. Phenotypic and functional analyses were carried out to
      compare these with that of fetal liver CD34 cell derived macrophages. As assessed
      by FACS analysis, the hES-CD34 cell derived macrophages displayed characteristic
      cell surface markers CD14, CD4, CCR5, CXCR4, and HLA-DR suggesting a normal
      phenotype. Tests evaluating phagocytosis, upregulation of the costimulatory
      molecule B7.1, and cytokine secretion in response to LPS stimulation showed that
      these macrophages are also functionally normal. When infected with HIV-1, the
      differentiated macrophages supported productive viral infection. Lentiviral
      vector transduced hES cells expressing the transgene GFP were evaluated similarly
      like above. The transgenic hES cells also gave rise to macrophages with normal
      phenotypic and functional characteristics indicating no vector mediated adverse
      effects during differentiation. CONCLUSION: Phenotypically normal and
      functionally competent macrophages could be derived from hES-CD34 cells. Since
      these cells are susceptible to HIV-1 infection, they provide a uniform source of
      macrophages for viral infection studies. Based on these results, it is also now
      feasible to transduce hES-CD34 cells with anti-HIV genes such as inhibitory
      siRNAs and test their antiviral efficacy in down stream differentiated cells such
      as macrophages which are among the primary cells that need to be protected
      against HIV-1 infection. Thus, the potential utility of hES derived CD34
      hematopoietic cells for HIV-1 gene therapy can be evaluated.

PMID- 16623951
TI  - Loss of interleukin-12 modifies the pro-inflammatory response but does not
      prevent duct obstruction in experimental biliary atresia.
AB  - BACKGROUND: Livers of infants with biliary atresia and of neonatal mice infected
      with rotavirus (RRV) have increased expression of interferon-gamma (IFNgamma) and
      interleukin (IL)-12. While the expression of IFNgamma regulates the obstruction
      of extrahepatic bile ducts by lymphocytes, the role of IL-12 in the pathogenesis
      of biliary obstruction is unknown. Based on the role of IL-12 as a key
      proinflammatory cytokine, we hypothesized that loss of IL-12 prevents the
      obstruction of extrahepatic bile ducts. METHODS: IL12-knockout (IL-12KO) and wild
      type mice were injected with RRV or saline at day 1 of age and monitored for the
      development of symptoms. The cellular and molecular phenotypes were determined at
      days 3, 7, and 14 by real-time PCR and flow cytometry. RESULTS: RRV infection of
      IL-12KO mice resulted in growth failure, jaundice/acholic stools, and decreased
      survival similar to wild-type mice. IL-12KO mice had a remarkable neutrophil-rich
      portal inflammation and epithelial sloughing of extrahepatic bile ducts. Loss of
      IL-12 decreased but did not abolish the hepatic expression of IFNgamma, displayed
      a remarkable increase in expression of TNFalpha, IFNalpha, IFNbeta and decreased
      expression of IL-4 and IL-5. CONCLUSION: Loss of IL-12 did not modify the
      progression of bile duct obstruction in experimental biliary atresia. However,
      the inflammatory response was predominantly neutrophil-based and displayed a Th1
      response in the absence of IL-12.

PMID- 16623952
TI  - Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma
      and is associated with poor prognosis in EGFR-overexpressing glioblastoma.
AB  - BACKGROUND: We previously identified brain type fatty acid-binding protein
      (FABP7) as a prognostic marker for patients with glioblastoma (GBM). Increased
      expression of FABP7 is associated with reduced survival. To investigate possible
      molecular mechanisms underlying this association, we compared the expression and
      subcellular localization of FABP7 in non-tumor brain tissues with different types
      of glioma, and examined the expression of FABP7 and epidermal growth factor
      receptor (EGFR) in GBM tumors. METHODS: Expression of FABP7 in non-tumor brain
      and glioma specimens was examined using immunohistochemistry, and its correlation
      to the clinical behavior of the tumors was analyzed. We also analyzed the
      association between FABP7 and EGFR expression in different sets of GBM specimens
      using published DNA microarray datasets and semi-quantitative
      immunohistochemistry. In vitro migration was examined using SF763 glioma cell
      line. RESULTS: FABP7 was present in a unique population of glia in normal human
      brain, and its expression was increased in a subset of reactive astrocytes. FABP7
      immunoreactivity in grade I pilocytic astrocytoma was predominantly cytoplasmic,
      whereas nuclear FABP7 was detected in other types of infiltrative glioma.
      Nuclear, not cytoplasmic, FABP7 immunoreactivity was associated with EGFR
      overexpression in GBM (N = 61, p = 0.008). Expression of the FABP7 gene in GBM
      also correlated with the abundance of EGFR mRNA in our previous microarray
      analyses (N = 34, p = 0.016) and an independent public microarray dataset (N =
      28, p = 0.03). Compared to those negative for both markers, nuclear FABP7
      positive/EGFR-positive and nuclear FABP7-positive/EGFR-negative GBM tumors
      demonstrated shortest survival, whereas those only positive for EGFR had
      intermediate survival. EGFR activation increased nuclear FABP7 immunoreactivity
      in a glioma cell line in vitro, and inhibition of FABP7 expression suppressed EGF
      induced glioma-cell migration. Our data suggested that in EGFR-positive GBM the
      presence of nuclear FABP7 immunoreactivity increases the risk of poor prognosis
      CONCLUSION: In this study, we identified a possible mechanism as the basis of the
      association between nuclear FABP7 and poor prognosis of GBM. FABP7 expression can
      be found in all grades of astrocytoma, but neoplastic cells with nuclear FABP7
      were only seen in infiltrative types of tumors. Nuclear FABP7 may be induced by
      EGFR activation to promote migration of GBM tumor cells. Positive nuclear FABP7
      and EGFR overexpression correlated with short survival in EGFR-positive GBM
      patients. Therefore, nuclear FABP7 immunoreactivity could be used to monitor the
      progression of EGFR-overexpressed GBM.

PMID- 16623953
TI  - An analysis of the Sargasso Sea resource and the consequences for database
      composition.
AB  - BACKGROUND: The environmental sequencing of the Sargasso Sea has introduced a
      huge new resource of genomic information. Unlike the protein sequences held in
      the current searchable databases, the Sargasso Sea sequences originate from a
      single marine environment and have been sequenced from species that are not
      easily obtainable by laboratory cultivation. The resource also contains very many
      fragments of whole protein sequences, a side effect of the shotgun sequencing
      method.These sequences form a significant addendum to the current searchable
      databases but also present us with some intrinsic difficulties. While it is
      important to know whether it is possible to assign function to these sequences
      with the current methods and whether they will increase our capacity to explore
      sequence space, it is also interesting to know how current bioinformatics
      techniques will deal with the new sequences in the resource. RESULTS: The
      Sargasso Sea sequences seem to introduce a bias that decreases the potential of
      current methods to propose structure and function for new proteins. In particular
      the high proportion of sequence fragments in the resource seems to result in poor
      quality multiple alignments. CONCLUSION: These observations suggest that the new
      sequences should be used with care, especially if the information is to be used
      in large scale analyses. On a positive note, the results may just spark
      improvements in computational and experimental methods to take into account the
      fragments generated by environmental sequencing techniques.

PMID- 16623954
TI  - The training and development needs of midwives in Indonesia: paper 2 of 3.
AB  - BACKGROUND: There is a shortfall in midwives in Indonesia (an estimated 26 per
      100,000 people), which means that the quality of antenatal, perinatal and
      postnatal care varies widely. One consequence of this is the high rate of
      maternal and perinatal mortality, which has prompted a number of health
      initiatives. The current study was part of a review of the existing complex
      system of midwifery training and the development of a coherent programme of
      continuing professional development, tighter accreditation regulations and
      clearer professional roles. Its aims were to identify the occupational profiles
      and development needs of the participating midwives, and to establish whether any
      differences existed between grades, geographical location and hospital/community
      midwives. METHODS: A psychometrically valid training-needs instrument was
      administered to 332 midwives from three provinces, covering both hospital and
      community staff and a range of midwifery grades. The instrument had the capacity
      to identify occupational roles and education/training needs of the respondents.
      RESULTS: The occupational roles of the midwives varied significantly by province,
      indicating regional service delivery distinctions, but very little difference in
      the roles of hospital and community midwives. The most educated midwives
      attributed more importance to 35 out of the 40 tasks, suggesting an implicit role
      distinction in terms of level of activity. All midwives reported significant
      training needs for all 40 tasks. The most-educated midwives recorded training
      needs for 24 tasks, while the less-educated had training requirements for all
      tasks, which suggests that new training programmes are effective. Few differences
      in training needs were revealed between hospital and community midwives
      CONCLUSION: The results from this survey suggest important regional differences
      in how the midwife's role is discharged and underline the importance of this sort
      of research, in order to ensure the suitability of basic and postbasic
      educational provision. The study also highlights the need for further development
      and training of midwives in a wide range of tasks. These results provide a
      systematic and reliable overview of current midwifery roles and development needs
      and could serve to inform future training.

PMID- 16623955
TI  - CCR3, CCR5, CCR8 and CXCR3 expression in memory T helper cells from allergic
      rhinitis patients, asymptomatically sensitized and healthy individuals.
AB  - BACKGROUND: Chemokine receptors have been suggested to be preferentially
      expressed on CD4+ T cells with CCR3 and CCR8 linked to the T helper (Th) 2 subset
      and CCR5 and CXCR3 to the Th1 subset, however this remains controversial.
      OBJECTIVE: Our aim was to compare the CCR3, CCR5, CCR8 and CXCR3 expression in
      memory Th cells from allergic, asymptomatically sensitized and healthy
      individuals. METHODS: Peripheral blood mononuclear cells from 8 pollen allergic
      rhinitis patients, 10 asymptomatically sensitized and 10 healthy individuals were
      stimulated for 7 days with allergen or tetanus toxoid. CCR3, CCR5, CCR8, CXCR3,
      CD4 and CD45RO were detected by flow cytometry. RESULTS: No differences in
      chemokine receptor expression were observed between the three groups on day 0,
      and seven days of unstimulated culture did not change the expression. Both
      antigenic stimuli increased the chemokine receptor expression, tetanus toxoid
      being the most potent. No differences in percentage chemokine receptor positive
      memory Th cells were observed between the three groups on day 7. Only a change in
      MFI for CCR5 was significantly different between the three groups after allergen
      stimulation of the Th cells. CONCLUSION: We conclude that even though allergen
      and antigen induced increased chemokine receptor expression, no differences in
      profiles were identified in memory Th cells from patient groups with different
      atopic status.

PMID- 16623956
TI  - Mastectomy or breast conserving surgery? Factors affecting type of surgical
      treatment for breast cancer--a classification tree approach.
AB  - BACKGROUND: A critical choice facing breast cancer patients is which surgical
      treatment--mastectomy or breast conserving surgery (BCS)--is most appropriate.
      Several studies have investigated factors that impact the type of surgery chosen,
      identifying features such as place of residence, age at diagnosis, tumor size,
      socio-economic and racial/ethnic elements as relevant. Such assessment of
      "propensity" is important in understanding issues such as a reported under
      utilisation of BCS among women for whom such treatment was not contraindicated.
      Using Western Australian (WA) data, we further examine the factors associated
      with the type of surgical treatment for breast cancer using a classification tree
      approach. This approach deals naturally with complicated interactions between
      factors, and so allows flexible and interpretable models for treatment choice to
      be built that add to the current understanding of this complex decision process.
      METHODS: Data was extracted from the WA Cancer Registry on women diagnosed with
      breast cancer in WA from 1990 to 2000. Subjects' treatment preferences were
      predicted from covariates using both classification trees and logistic
      regression. RESULTS: Tumor size was the primary determinant of patient choice,
      subjects with tumors smaller than 20 mm in diameter preferring BCS. For subjects
      with tumors greater than 20 mm in diameter factors such as patient age, nodal
      status, and tumor histology become relevant as predictors of patient choice.
      CONCLUSION: Classification trees perform as well as logistic regression for
      predicting patient choice, but are much easier to interpret for clinical use. The
      selected tree can inform clinicians' advice to patients.

PMID- 16623957
TI  - How dietary arachidonic- and docosahexaenoic- acid rich oils differentially
      affect the murine hepatic transcriptome.
AB  - INTRODUCTION: Herein, we expand our previous work on the effects of long chain
      polyunsaturated fatty acids (LC-PUFA) on the murine hepatic transcriptome using
      novel statistical and bioinformatic approaches for evaluating microarray data.
      The analyses focuses on key differences in the transcriptomic response that will
      influence metabolism following consumption of FUNG (rich in 20:4n6), FISH (rich
      in 20:5n3, 22:5n3, and 22:6n3) and COMB, the combination of the two. RESULTS:
      Using a variance-stabilized F-statistic, 371 probe sets (out of 13 K probe sets
      in the Affymetrix Mu11K chip set) were changed by dietary treatment (P < 0.001).
      Relative to other groups, COMB had unique affects on murine hepatic transcripts
      involved in cytoskeletal and carbohydrate metabolism; whereas FUNG affected amino
      acid metabolism via CTNB1 signaling. All three diets affected transcripts linked
      to apoptosis and cell proliferation, with evidence FISH may have increased
      apoptosis and decreased cell proliferation via various transcription factors,
      kinases, and phosphatases. The three diets affected lipid transport, lipoprotein
      metabolism, and bile acid metabolism through diverse pathways. Relative to other
      groups, FISH activated cyps that form hydroxylated fatty acids known to affect
      vascular tone and ion channel activity. FA synthesis and delta 9 desaturation
      were down regulated by COMB relative to other groups, implying that a FA mixture
      of 20:4n6, 20:5n3, and 22:6n3 is most effective at down regulating synthesis, via
      INS1, SREBP, PPAR alpha, and TNF signaling. Heme synthesis and the utilization of
      heme for hemoglobin production were likely affected by FUNG and FISH. Finally,
      relative to other groups, FISH increased numerous transcripts linked to combating
      oxidative such as peroxidases, an aldehyde dehydrogenase, and heat shock
      proteins, consistent with the major LC-PUFA in FISH (20:5n3, 22:5n3, 22:6n3)
      being more oxidizable than the major fatty acids in FUNG (20:4n6). CONCLUSION:
      Distinct transcriptomic, signaling cascades, and predicted affects on murine
      liver metabolism have been elucidated for 20:4n6-rich dietary oils, 22:6n3-rich
      oils, and a surprisingly distinct set of genes were affected by the combination
      of the two. Our results emphasize that the balance of dietary n6 and n3 LC-PUFA
      provided for infants and in nutritional and neutraceutical applications could
      have profoundly different affects on metabolism and cell signaling, beyond that
      previously recognized.

PMID- 16623958
TI  - Comparison of age-specific cataract prevalence in two population-based surveys 6
      years apart.
AB  - BACKGROUND: In this study, we aimed to compare age-specific cortical, nuclear and
      posterior subcapsular (PSC) cataract prevalence in two surveys 6 years apart.
      METHODS: The Blue Mountains Eye Study examined 3654 participants (82.4% of those
      eligible) in cross-section I (1992-4) and 3509 participants (75.1% of survivors
      and 85.2% of newly eligible) in cross-section II (1997-2000, 66.5% overlap with
      cross-section I). Cataract was assessed from lens photographs following the
      Wisconsin Cataract Grading System. Cortical cataract was defined if cortical
      opacity comprised > or = 5% of lens area. Nuclear cataract was defined if nuclear
      opacity > or = Wisconsin standard 4. PSC was defined if any present. Any cataract
      was defined to include persons who had previous cataract surgery. Weighted kappa
      for inter-grader reliability was 0.82, 0.55 and 0.82 for cortical, nuclear and
      PSC cataract, respectively. We assessed age-specific prevalence using an interval
      of 5 years, so that participants within each age group were independent between
      the two surveys. RESULTS: Age and gender distributions were similar between the
      two populations. The age-specific prevalence of cortical (23.8% in 1st, 23.7% in
      2nd) and PSC cataract (6.3%, 6.0%) was similar. The prevalence of nuclear
      cataract increased slightly from 18.7% to 23.9%. After age standardization, the
      similar prevalence of cortical (23.8%, 23.5%) and PSC cataract (6.3%, 5.9%), and
      the increased prevalence of nuclear cataract (18.7%, 24.2%) remained. CONCLUSION:
      In two surveys of two population-based samples with similar age and gender
      distributions, we found a relatively stable cortical and PSC cataract prevalence
      over a 6-year period. The increased prevalence of nuclear cataract deserves
      further study.

PMID- 16623959
TI  - Cloning and expression analysis of two distinct HIF-alpha isoforms--gcHIF-1alpha
      and gcHIF-4alpha--from the hypoxia-tolerant grass carp, Ctenopharyngodon idellus.
AB  - BACKGROUND: Hypoxia-inducible factors (HIFs) are involved in adaptive and
      survival responses to hypoxic stress in mammals. In fish, very little is known
      about the functions of HIFs. RESULTS: We have cloned and characterized two
      distinct HIF-alpha cDNAs--gcHIF-1alpha and gcHIF-4alpha--from the hypoxia
      tolerant grass carp. The deduced gcHIF-1alpha protein is highly similar to the
      HIF-1alphas (57-68%) from various vertebrate species, while gcHIF-4alpha is a
      novel isoform, and shows an equivalent degree of amino acid identity (41-47%) to
      the HIF-1alpha, HIF-2alpha and HIF-3alpha proteins so far described. Parsimony
      analysis indicated that gcHIF-4alpha is most closely related to the HIF-3alpha
      proteins. Northern blot analysis showed that mRNA levels of gcHIF-1alpha and
      gcHIF-4alpha differ substantially under normoxic and hypoxic conditions, while
      Western blot studies demonstrated that the endogenous protein levels for both
      gcHIF-1alpha and gcHIF-4alpha are similarly responsive to hypoxia. Our findings
      suggest that both gcHIF-1alpha and gcHIF-4alpha are differentially regulated at
      the transcriptional and translational levels. HRE-luciferase reporter assays show
      that both proteins function as transcription activators and play distinct roles
      in modulating the hypoxic response in grass carp. CONCLUSION: There are at least
      two distinct HIF-alpha isoforms--gcHIF-1alpha and gcHIF-4alpha--in the hypoxia
      tolerant grass carp, which are differentially expressed and regulated in
      different fish organs in response to hypoxic stress. Overall, the results suggest
      that unique molecular mechanisms operate through these two HIF-alpha isoforms,
      which underpin the hypoxic response in the hypoxia-tolerant grass carp.

PMID- 16623960
TI  - A3 adenosine receptors and mitogen-activated protein kinases in lung injury
      following in vivo reperfusion.
AB  - INTRODUCTION: Although activation of A3 adenosine receptors attenuates
      reperfusion lung injury and associated apoptosis, the signaling pathway that
      mediates this protection remains unclear. Adenosine agonists activate mitogen
      activated protein kinases, and these kinases have been implicated in
      ischemia/reperfusion injury; the purpose of this study was therefore to determine
      whether A3 adenosine receptor stimulation with reperfusion modulates expression
      of the different mitogen-activated protein kinases. In addition, we compared the
      effect of the A3 adenosine agonist IB-MECA with the newly synthesized, highly
      selective A3 adenosine receptor agonist MRS3558 on injury in reperfused lung.
      METHOD: Studies were performed in an in vivo spontaneously breathing cat model,
      in which the left lower lobe of the lung was isolated and subjected to 2 hours of
      ischemia and 3 hours of reperfusion. The selective A3 adenosine receptor agonists
      IB-MECA (0.05 mg/kg, 0.1 mg/kg, or 0.3 mg/kg) and MRS3558 (0.05 mg/kg or 0.1
      mg/kg) were administered before reperfusion. RESULTS: Both A3 adenosine receptor
      agonists administered before reperfusion markedly (P < 0.01) attenuated indices
      of injury and apoptosis, including the percentage of injured alveoli, wet/dry
      weight ratio, myeloperoxidase activity, TUNEL (in situ TdT-mediated dUTP nick end
      labeling)-positive cells, and caspase 3 activity and expression. The more
      pronounced effects at low doses were observed with MRS3558. Increases in
      phosphorylated c-Jun amino-terminal protein kinase (JNK), p38, and extracellular
      signal-regulated kinase (ERK)1/2 levels were observed by the end of reperfusion
      compared with controls. Pretreatment with the A3 agonists upregulated
      phosphorylated ERK1/2 levels but did not modify phosphorylated JNK and p38
      levels. CONCLUSION: The protective effects of A3 adenosine receptor activation
      are mediated in part through upregulation of phosphorylated ERK. Also, MRS3558
      was found to be more potent than IB-MECA in attenuating reperfusion lung injury.
      The results suggest not only that enhancement of the ERK pathway may shift the
      balance between cell death and survival toward cell survival, but also that A3
      agonists have potential as an effective therapy for ischemia/reperfusion-induced
      lung injury.

PMID- 16623961
TI  - A dopamine transporter polymorphism is a risk factor for borderline personality
      disorder in depressed patients.
AB  - BACKGROUND: Borderline personality disorder (BPD) is often co-morbid with major
      depression and may complicate its treatment. We were interested in differences in
      genetic and developmental risk factors between depressed patients with or without
      a co-morbid BPD. METHOD: Out-patients with major depressive disorder were
      recruited for two treatment trials. Assessment of depressed patients included the
      assessment of personality disorders, developmental risk factors and DNA samples
      for genetic analyses. RESULTS: In each study there was a significant association
      between the 9-repeat allele of the dopamine transporter (DAT1) and BPD, with odds
      ratios (OR) > 3 and p < or = 0.02. This association remained significant when
      developmental risk factors for BPD (childhood abuse and neglect and borderline
      temperament) were also included in the analyses. The OR was even larger in the
      depressed patients aged > or = 35 years (OR 9.31, p = 0.005). CONCLUSION: This
      replicated association in depressed patients between the 9-repeat allele of DAT1
      and BPD may provide clues to understanding the neurobiology of BPD. The finding
      that the association is larger in the older depressed patients, suggests that the
      9-repeat allele may be associated with a poorer prognosis BPD, rather than a
      young adult limited variant of BPD.

PMID- 16623962
TI  - Depressive symptoms and C-reactive protein: the Cardiovascular Risk in Young
      Finns Study.
AB  - BACKGROUND: We tested the hypothesis that depressive symptoms in healthy young
      adults would be associated with elevated levels of C-reactive proteins (CRP).
      METHOD: We studied the association between depressive symptoms and CRP in 1201
      young adults, as a part of the on-going population-based Cardiovascular Risk in
      Young Finns Study. Depressive symptoms were determined by responses to a revised
      version of Beck's Depression Inventory in 1992 and 2001. CRP and other known
      cardiac risk factors were measured in 2001. RESULTS: Higher depressive
      symptomatology in 1992 and in 2001 and their means score were related to higher
      CRP levels (B's range from 0.24 to 0.21, p < 0.001). These relationships
      persisted after separate adjustments for various risk factors including sex, age,
      education, oral contraceptive use, dietary fat, physical activity, alcohol
      consumption, smoking status, LDL-cholesterol, HDL-cholesterol, systolic blood
      pressure and history of acute infectious disease. Adjustments for obesity and
      triglycerides levels, however, somewhat attenuated the relationship between
      depressive symptoms and CRP. CONCLUSIONS: We concluded that higher levels of
      depressive symptoms are associated with higher levels of CRP, but this
      association may largely be attributable to obesity or triglycerides.

PMID- 16623963
TI  - Treatment efficacy and regulatory host responses in chronic experimental
      Schistosoma bovis infections in goats.
AB  - The aim of this study was to elucidate the regulatory responses and the long-term
      effect of praziquantel treatment in chronically Schistosoma bovis-infected West
      African Dwarf goats. Forty-two goats were used and the design comprised a primary
      infection followed by treatment at week 13, challenge infection at week 36 and
      termination at week 52. Dependent variables included clinico-pathological data,
      worm numbers, faecal and tissue egg counts, and gross pathology of the liver. The
      results showed that primary infections remained suppressed for up to 52 weeks
      and, although challenge infections imposed on 36-week-old primary infections
      established fully, the impairment of their egg production capacity provided
      protection against clinico-pathological consequences measured by body weight and
      haemoglobin levels. The study also confirmed a high efficacy (97.7%) of
      praziquantel for treatment of S. bovis infection in goats and showed that
      anthelminthic removal of primary infections does not interfere with the ability
      of the goat to elicit a marked resistance to a subsequent challenge infection.
      Although treated goats had more fibrous scarring of livers than untreated goats,
      no negative effects of liver lesions were reflected in weight gains of treated
      goats. This study provides strong evidence for the beneficial effects of
      anthelminthic treatment of young domestic stock as an element of treatment and
      preventive programmes.

PMID- 16623964
TI  - Robinia aurata n. g., n. sp. (Digenea: Hemiuridae) from the mugilid Liza aurata
      with a molecular confirmation of its position within the Hemiuroidea.
AB  - Robinia aurata n. g., n. sp. is described from Liza aurata (Mugilidae), the
      golden grey mullet, from the Ebro Delta, Spanish Mediterranean. The new genus
      differs from all other hemiurid genera in the combined possession of muscular
      flanges and a vestigial ecsoma. Within the Bunocotylinae, which currently
      accommodates 2 genera, Bunocotyle and Saturnius, the new genus exhibits a unique
      combination of blind caeca, Juel's organ, post-ovarian bulk of the uterus in the
      hind-body, and tegumental papillae surrounding the oral and ventral sucker
      apertures. Furthermore, Robinia n. g. differs from both Bunocotyle and Saturnius
      in the nature of the muscular extensions around the oral sucker, with the shape
      of a muscular belt in the latter and numerous muscular papillae in the former.
      The phylogenetic hypothesis for the Bunocotylinae developed from sequence data
      analyses based on partial lsrDNA and complete ssrDNA combined (22 species) and V4
      domain of the ssrRNA gene (37 species) supports the erection of the new genus and
      confirms its position within the Hemiuroidea. Both molecular analyses confirmed
      the monophyly of the Hemiuroidea, its division into 2 major clades and the
      polyphyly of the Derogenidae, as in previous studies, and suggest that the
      Gonocercinae (with 2 genera, Gonocerca and Hemipera), may require a distinct
      familial status. Finally, there was poor support for the distinct status of the
      Lecithasteridae and Hemiuridae, following previous suggestions based on different
      sequence data sets. A key to genera of the Bunocotylinae is presented.

PMID- 16623965
TI  - Evidence of intestinal parasites of dinosaurs.
AB  - Protozoan cysts and helminth eggs preserved in a coprolite from the Early
      Cretaceous Bernissart Iguanodon shaft in Belgium demonstrate that representatives
      of 3 phyla parasitized dinosaurs by that period. These fossil parasite stages are
      described and their possible effect on dinosaurs discussed. These findings
      represent the earliest fossil records of protozoan and helminth parasites of
      terrestrial vertebrates.

PMID- 16623966
TI  - Prolonged diapause in the ectoparasite Carnus hemapterus (Diptera: Cyclorrhapha,
      Acalyptratae) - how frequent is it in parasites?
AB  - Prolonged diapause is usually interpreted as an adaptation to unpredictable
      environmental conditions and resource availability. Many parasites usually face
      highly unpredictable environments, therefore prolonged diapause should be common
      among these organisms. Here we examine the occurrence and frequency of prolonged
      diapause in the ectoparasite Carnus hemapterus (Diptera: Cyclorrhapha,
      Acalyptratae). We found that the studied population is polymorphic with respect
      to diapause duration. Emergence of carnid flies after 2 and 3 wintering seasons
      was therefore detected in around 17% and 21% of the samples respectively. The
      number of flies with prolonged diapause ranked 0.88-50% with respect to the
      number of flies emerging during the first spring. Both the occurrence of
      prolonged diapause and the number of flies with a long life-cycle are related to
      the number of flies emerging during the first spring. The emergence pattern of
      flies with prolonged diapause was very similar to that observed for flies with a
      short cycle and occurred in synchrony with the occurrence of hosts. Prolonged
      diapause has been frequently reported in plant-feeding insects and in some host
      parasitoid systems, but this is, to our knowledge, the second report ever on
      prolonged diapause in true parasites of animals. We discuss the reasons for the
      apparent rarity of prolonged diapause among these organisms.

PMID- 16623967
TI  - Preferential infection of dividing cells by Cryptosporidium parvum.
AB  - In spite of its limitations, the culture of Cryptosporidium parvum in monolayers
      of epithelial cells is a suitable model to study the interaction of this
      protozoan parasite with the host cell, to assay oocyst infectivity, and to screen
      drugs for anti-cryptosporidial activity. For unknown reasons, growth of
      Cryptosporidium in culture is limited in time and generally does not lead to the
      production of significant numbers of oocysts. In monolayers infected with high
      doses of oocysts, we observed that many cells remain uninfected, suggesting that
      some cells are less susceptible to the infection. Since C. parvum and the related
      species C. hominis lack many essential biosynthetic pathways, we tested whether
      the dependence of the parasite on host cell metabolites may favour the infection
      of cells in mitosis. The proportion of monolayer cells in stationary (G0/G1)
      phase and in mitosis (S/G2/M) was determined and the prevalence of infected cells
      in each subpopulation was quantified. Although C. parvum infects and develops in
      dividing and stationary cells, a significant preference for cells in S/G2/M phase
      was observed. Consistent with previous observations showing that C. parvum
      induces apoptosis in cell monolayers, infection was accompanied by a significant
      increase in the proportion of mitotic cells.

PMID- 16623968
TI  - Preliminary results on correlation between neural response imaging and 'most
      comfortable levels' in cochlear implantation.
AB  - During cochlear implantation, precise placement of the cochlear electrodes
      against the cochlear nerve is one of the most important steps, necessary to
      enable the patient to be aware of the stimulus from the implanted device. Neural
      response imaging (NRI) is a new tool which measures the evoked compound action
      potential generated as a result of electrical stimulation of the cochlea by
      properly placed electrodes during surgery. The aim of this study was to examine
      the correlation between intra-operative NRI recordings and 'most comfortable
      levels' (M levels) measured during standard fitting with the SoundWave fitting
      software, in cochlear implantation patients. Seven adult subjects were included
      in the study. The average duration of profound bilateral deafness was seven years
      (range = 19 years) and the mean age at implantation was 24 years (range = 17-34
      years). All subjects underwent implantation and reached the one-month fitting
      session; one patient reached the two-month fitting session. The intra-operative
      NRI threshold (tNRI) was observed to be much higher than the first fitting M
      levels. The tNRI was 203 per cent of the sequential M value and 246 per cent of
      the paired M value. All but one intra-operative tNRI values were greater than 150
      clinical units (CU), and all first fitting M levels were on average below 100 CU.
      No obvious correlation was found between individual intra-operative tNRI and
      first fitting M levels. The M levels at one month were much higher than the first
      fitting M levels, with much more dispersion.

PMID- 16623969
TI  - Management of stenosis and acquired atresia of the external auditory meatus.
AB  - The aim of this study was to investigate the aetiology of acquired atresia and
      stenosis of the external auditory meatus and to present our results for surgical
      management. Over an 18-year period (from 1986 to 2004), data were collected
      prospectively from patient cohorts in Dundee and Edinburgh. Stenosis of the
      auditory meatus was due to chronic otitis externa in 64 per cent of cases,
      compared with 37 per cent of cases with acquired atresia; the latter had instead
      a history of chronic suppurative otitis media in 43 per cent. Surgical treatment
      of canal stenosis with meatoplasty alone achieved a widely patent ear canal in 80
      per cent of cases, with 78 per cent of ears remaining free of discharge. Cases of
      acquired atresia treated with simple surgical excision of the soft tissue plug
      experienced a 100 per cent failure rate. The additional use of a split skin graft
      achieved a patent meatus in 70 per cent of cases, with hearing improvement in 79
      per cent. However, the ear canal remained unstable and late recurrence was
      observed.

PMID- 16623970
TI  - Incidence of complementary therapy use in patients undergoing vestibular
      assessment.
AB  - OBJECTIVES: To determine the incidence of use of complementary therapies in
      patients with vestibular symptoms undergoing vestibular assessment. DESIGN: A
      prospective, questionnaire-based study. SETTING: A UK university hospital
      department of audiology with secondary and tertiary referrals. PARTICIPANTS: A
      consecutive series of 80 patients seen for vestibular assessment between November
      2004 and May 2005. MAIN OUTCOME MEASURES: Use of complementary therapies; actual
      therapies used and patients' subjective opinion of efficacy. RESULTS: Thirteen
      patients (16 per cent) had tried some form of complementary therapy for their
      vestibular symptoms. Ginkgo biloba and acupuncture were the two most popular
      treatments. Seven patients made their decision as to which treatment to try on
      the basis of personal recommendation. Six of the 13 patients (46 per cent)
      reported that their choice of treatment(s) helped them. CONCLUSIONS: Sixteen per
      cent of patients seen for vestibular assessment had tried some form of
      complementary therapy for their vestibular symptoms. Clinicians should be aware
      of this and of the potential interactions between complementary therapies and
      conventional medicine.

PMID- 16623971
TI  - Ear, nose and voice problems in children with orofacial clefts.
AB  - The purpose of this study was to compare the prevalence of ear, nose and
      particularly voice problems in groups of children with cleft palate (CP) and with
      unilateral cleft lip, alveolus and palate (UCLP). On the basis of history,
      regular otorhinolaryngological examinations and hearing tests, the prevalence of
      different pathologies was assessed in 80 CP children (35 boys and 45 girls) and
      73 UCLP children (47 boys and 26 girls). Ear pathology was reported in 53.8 per
      cent of CP children and in 58.9 per cent of UCLP children. Nasal breathing was
      impaired in 14 CP (17.5 per cent) and 36 UCLP (49.3 per cent) children. Dysphonia
      was detected in 12.5 per cent of CP and 12.3 per cent of UCLP children. In 9.2
      per cent of all cleft children, functional voice disorder caused a hoarse voice.
      Two-thirds of cleft children with functional dysphonia had protracted hearing
      loss. Therefore, ENT specialists must take an active role early in the treatment
      of children with clefts.

PMID- 16623972
TI  - Aerodynamic, acoustic and functional results of posterior transverse laser
      cordotomy for bilateral abductor vocal fold paralysis.
AB  - Bilateral abductor vocal fold paralysis (BAVFP) is a rare but life-threatening
      condition which may require an emergency tracheotomy procedure. The ideal
      surgical technique for this condition should improve quality of life by relieving
      the airway obstruction while preserving laryngeal functions such as phonation and
      deglutition. Posterior transverse laser cordotomy (PTLC) was first described by
      Dennis and Kashima as a technique for providing an airway at the posterior
      glottis without pre-operative tracheotomy; they reported it as a successful
      method with satisfactory functional results. The aim of this prospective study
      was to evaluate long term acoustic, aerodynamic and functional results of the
      primary bilateral PTLC technique in 22 BAVFP patients. Severity of dyspnoea was
      evaluated using a five-level subjective symptom scale graded according to the
      limitation in daily activity and level of respiratory difficulty. Aerodynamic and
      acoustic analyses were performed pre-operatively and prospective changes in
      aerodynamic and acoustic parameters were collected after one post-operative year.

PMID- 16623973
TI  - Immunohistochemical detection of E-cadherin in certain types of salivary gland
      tumours.
AB  - OBJECTIVES: To investigate the topography of E-cadherin and its possible
      correlation with the histological phenotype of salivary gland tumours. MATERIAL
      AND METHODS: Archival formalin-fixed, paraffin-embedded sections of 54 benign and
      56 malignant tumours and 24 samples of normal and inflamed salivary gland tissue
      were studied immunohistochemically using an Envision/horseraddish peroxidase
      (HRP) technique. RESULTS: In normal and inflamed salivary gland samples, E
      cadherin was expressed at the membrane of acinar, myoepithelial and ductal cells
      located at cell-cell contact points. Reduction and/or absence of E-cadherin was
      only observed in pleomorphic adenoma at the peripheral cells of the duct-like or
      island structures, or in the cells exhibiting plasmacytoid or stromal
      differentiation. Neoplastic epithelium in Warthin's tumours and in myoepithelial
      and oncocytic adenomas was strongly positive. Furthermore, a weak to moderate
      loss of expression which was related to tissue tumour subtype was seen in
      malignant tumours such as: adenoid cystic carcinomas; polymorphous low-grade
      adenocarcinomas; acinic cell carcinomas; and mucoepidermoid low-grade, epithelial
      myoepithelial, lymphoepithelial and squamous low-grade carcinomas. Moderate to
      extreme loss or alternative cytoplasmic non-functional expression were observed
      in cases of salivary ductal carcinoma, carcinosarcoma, myoepithelial carcinoma,
      oncocytic adenocarcinoma, unspecified adenocarcinoma and squamous high-grade
      carcinomas. CONCLUSION: This study suggests a direct association of E-cadherin
      expression with neoplastic histologic phenotype, which is lost in the more
      undifferentiated and invasive epithelial salivary gland tumours.

PMID- 16623974
TI  - Deep neck infection as the main initial presentation of primary head and neck
      cancer.
AB  - OBJECTIVES: Primary head and neck cancer and deep neck infection are not
      uncommon, but deep neck infection as the initial presentation of primary head and
      neck cancer is rare and these patients risk potential misdiagnosis. MATERIALS AND
      METHODS: The records of 301 patients with deep neck infection and 3,337 patients
      with primary head and neck cancers from 1990 to 2002 were retrospectively
      reviewed. Patients with primary head and neck cancers who had deep neck infection
      as their initial presentation were enrolled. RESULTS: Seven patients were
      identified (six men and one woman). The median age was 64 years. All patients
      presented with painful, erythematous neck swelling and all image studies showed
      abscess formation. Four abscesses received needle aspiration and three received
      surgical drainage, which yielded malignant cells in four specimens. The primary
      origins of malignancies were the nasopharynx (two patients), oropharynx (two
      patients), hypopharynx (one patient), parotid gland (one patient) and maxillary
      sinus (one patient). All patients had stage IV disease. Only three patients could
      receive curative therapy and only one patient was disease-free after three years.
      CONCLUSION: We suggest that detailed history-taking, complete examination of the
      ENT field and pathological study of the infected tissue must be performed for
      patients with deep neck infection to enable early detection and prompt treatment
      of any underlying malignancy.

PMID- 16623975
TI  - Acute epiglottitis in adults: a recent experience with 10 cases.
AB  - OBJECTIVES: Our objective was to examine the presentation, clinical course and
      management of acute epiglottitis in a recent series of adult patients. METHOD:
      All consecutive adults with acute epiglottitis or supraglottitis admitted to a
      tertiary referral centre over a recent six-month period were included in this
      retrospective study. The diagnosis of epiglottitis or supraglottitis was
      established by flexible nasolaryngoscopy. RESULTS: Ten patients were included.
      Two patients had concurrent acute tonsillitis and one had a peritonsillar
      abscess. Blood cultures were negative in all cases. Pathogens were isolated by
      throat swabs only in the two patients with acute tonsillitis. Two patients
      underwent intubation for management of airway obstruction. A combination of
      cefotaxime and metronidazole was the most common antibiotic regimen used.
      CONCLUSION: The rising incidence of acute epiglottitis in the adult population
      mandates vigilance on the part of the otolaryngologist. Selective airway
      intervention is recommended for patients with airway obstruction of more than 50
      per cent.

PMID- 16623976
TI  - Patient perceptions of the otolaryngology ward round in a teaching hospital.
AB  - OBJECTIVE: This survey assesses patients' perceptions of a daily otolaryngology
      ward round in a teaching hospital. METHODS: Initial, open-ended questionnaires
      generated themes from which a structured questionnaire was constructed. Patients'
      perceptions in a wide range of areas were examined by asking them to indicate on
      a Likert scale the extent to which they agreed or disagreed with a number of
      statements concerning various aspects of the ward round. RESULTS: One hundred
      patients were surveyed. The response rate was 79 per cent. The findings showed
      overall patient satisfaction with the ward round, particularly in the areas of
      information-giving regarding diagnosis, treatment and follow-up arrangements. The
      large size of the ward round appeared to be intimidating and induced anxiety for
      approximately one-third of patients. Patients wished the roles of staff present
      to be better defined and to be informed of the presence of medical students. One
      third of patients perceived staff to use language that was difficult to
      understand. CONCLUSIONS: The survey identified some improvement opportunities and
      will assist our department with its on-going endeavours to improve the ward round
      experience for both patients and staff.

PMID- 16623977
TI  - Simple keel fixation technique for endoscopic repair of anterior glottic
      stenosis.
AB  - The use of keels in the treatment of anterior glottic stenosis is well
      established. A variety of methods for keel fixation have previously been
      documented. We describe a simple technique of securing a Silastic keel, placed
      endoscopically, with a simple percutaneous suture, after laser vaporization of an
      anterior commissure web.

PMID- 16623978
TI  - Transnasal, intracranial penetrating injury treated endoscopically.
AB  - Intracranial penetrating injury through the nose is uncommon. We present the case
      of a four-year-old girl who sustained a transnasal, intracranial penetrating
      injury with a sharp wooden object. We performed endoscopic removal of the foreign
      body and repair of the associated cerebrospinal fluid fistula.

PMID- 16623979
TI  - Bilateral aplasia of parotid glands correlated with accessory parotid tissue.
AB  - Congenital absence of major salivary glands, especially the parotid gland, is a
      rare entity. It is usually monolateral and is not correlated with accessory
      salivary gland tissue. Aplasia of parotid gland may occur alone or in association
      with abnormalities of other salivary glands, first branchial arch developmental
      disturbances or other congenital anomalies.We report an interesting case of
      bilateral aplasia of the parotid glands together with bilateral accessory parotid
      tissue, without other congenital or developmental anomalies, and we describe the
      clinical and radiological findings.

PMID- 16623980
TI  - Recurring bilateral parotid gland swelling: two cases of sialodochitis fibrinosa.
AB  - Salivary gland swelling is a commonly encountered clinical symptom, but the
      establishment of a diagnosis is occasionally difficult. Here, we present two
      sialodochitis fibrinosa patients with recurring bilateral parotid swelling. In
      both patients, secretion of mucous plugs containing numerous eosinophils was
      observed from Stensen's ducts. As expected, the level of interleukin-5 in the
      saliva was much higher than that in the serum. One patient had no medical history
      of allergic disease; the other had allergic rhinitis which had never been
      associated with parotid gland swelling. Microbiological examination was unable to
      isolate significant bacterial specimens from the mucous plugs. Thus, although
      allergy and/or bacterial infection are reportedly implicated as causes of
      sialodochitis fibrinosa, there may exist other possibilities for its
      pathogenesis. Interleukin-5 seems to play a crucial role in the pathogenesis of
      sialodochitis fibrinosa.

PMID- 16623981
TI  - Synchronous bilateral tonsillar carcinoma: role of fluoro-deoxyglucose positron
      emission tomography scanning in detecting occult primary tumours in metastatic
      nodal disease of the head and neck.
AB  - We present the second case of primary synchronous bilateral tonsillar squamous
      cell carcinoma reported in the English literature and evaluate the role of fluoro
      deoxyglucose positron emission tomography scanning in the search for the occult
      primary tumour in a patient presenting with metastatic nodal disease in the head
      and neck.

PMID- 16623982
TI  - Papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma:
      treatment outcome and prognosis.
AB  - Papillary thyroid carcinoma with nodular fasciitis-like stroma (PTC-NFS) is one
      of the extremely rare variants of papillary thyroid carcinoma. To date, the
      majority of reported cases have been published in the surgical pathology and
      cytopathology literature, addressing the diagnostic difficulties posed by the
      condition's extensive, reactive stromal proliferation. Because of the rarity of
      PTC-NFS among papillary thyroid carcinoma variants, it has been unexplored from a
      clinical viewpoint. A MEDLINE search on the clinical course, role of radioiodine,
      treatment outcome and long term follow up of this disease yielded no result.We
      report the clinicoradiologic and histopathologic profile, together with post
      treatment long term follow up, in a 35-year-old woman harbouring this rare
      entity. To the best of our knowledge, this is the first report of a five-year
      follow up of this rare variant of PTC following total thyroidectomy and
      radioiodine treatment. Our follow-up findings reiterate the disease's favourable
      clinical course when managed in the same manner as a classical, differentiated
      papillary carcinoma of the thyroid, akin to that predicted by the pathologists,
      and emphasize the importance of differentiating PTC-NFS as a separate entity from
      the papillary carcinoma variants with aggressive histology. Given the rarity of
      this condition, the experience gained from the present case is a useful addition
      to the current knowledge on disease prognostication and management.A systematic
      review of the existing literature on PTC-NFS, including the case reported in the
      present paper, is also carried out, aiming to explore the patient characteristics
      and clinical behaviour pattern of this rare entity and to make appropriate
      recommendations on management strategy. The age of presentation ranges from 20 to
      82 years, with a mean of 44.5 years. Female preponderance was observed, with a
      female to male ratio of 3ratio1. No racial predilection was observed. Tumour size
      varied from 2 to 9 cm along its greatest diameter (mean = 4.3 cm). Metastasis to
      lymph nodes at presentation occurred in 25 per cent of cases. Metastasis to
      surrounding structures (e.g. parathyroid and skeletal muscle) was observed in
      12.5 per cent. There have been no reports of pulmonary or skeletal metastasis at
      presentation.

PMID- 16623983
TI  - Rare cases of Meniere's disease in children.
AB  - Classical Meniere's disease is rarely found in children and literature regarding
      it is scarce. In general, the frequency of Meniere's disease in children is only
      0.4-7.0 per cent of that in adults. The progression pattern of Meniere's disease
      in children is not known well. Here, we report three cases of Meniere's disease
      in children less than 15 years old, treated over nine years. The three cases
      comprise 14- and 13-year-old boys and a nine-year-old girl. Two of the three
      patients initially complained only of recurrent bouts of vertigo, without any
      tinnitus, ear fullness or hearing impairment. In all three cases, the early pure
      tone audiograms showed only high tone frequency loss, regardless of subjective
      hearing loss, and the decrease in the hearing threshold was observed one to eight
      years after the dizziness attacks began. The hearing threshold was usually
      decreased to a level of mild or moderate hearing impairment. After diuretic
      treatment, vertigo was generally well controlled, and some cases showed
      improvement in hearing. Of the total number of patients with Meniere's disease
      who visited our department over nine years, 2.6 per cent (3/114) were children,
      and the overall incidence of Meniere's disease in children with vertigo was 2.0
      per cent (3/147). In conclusion, Meniere's disease in children rarely develops
      and may have characteristics of high tone loss in initial audiograms.

PMID- 16623984
TI  - Management of globus pharyngeus: review of 699 cases.

PMID- 16623986
TI  - A recurring outbreak of Shigella sonnei among traditionally observant Jewish
      children in New York City: the risks of daycare and household transmission.
AB  - Dispersed community outbreaks of Shigella sonnei have occurred cyclically among
      traditionally observant Jews in the United States. In February 2000, we
      investigated a S. sonnei outbreak in one Jewish community in New York City. To
      determine risk factors for introduction of infection into households, we
      conducted a cohort study of households to compare risk factors for illness among
      primary subjects within households and age-matched well siblings. Isolates were
      subtyped by pulsed-field gel electrophoresis (PFGE). We used a random effects
      model to assess extra-household vs. intra-household transmission in households
      with multiple ill household members. Daycare or pre-school attendance [matched
      odds ratio (mOR) 16.1, P<0.001] and age <60 months (mOR 6.3, P<0.001) were
      independently associated with index subject illness. Outbreak isolates were
      closely related by PFGE analysis to the strain previously observed in Jewish
      community outbreaks. The random effects model strongly indicated that multiple
      illnesses in a single household are due to secondary transmission. Disease
      containment efforts should focus on reducing Shigella transmission in childcare
      settings and within homes.

PMID- 16623987
TI  - Antibiotic resistance of retail food and human Campylobacter isolates on the
      island of Ireland from 2001-2002.
AB  - The antimicrobial resistance profiles of Campylobacter isolates recovered from a
      range of retail food samples (n=374) and humans (n=314) to eight antimicrobial
      compounds were investigated. High levels of resistance in food C. jejuni isolates
      were observed for ceftiofur (58%), ampicillin (25%) and nalidixic acid (17%) with
      lower levels observed for streptomycin (7.9%) and chloramphenicol (8.3%). A total
      of 80% of human C. jejuni isolates were resistant to ceftiofur, while 17% showed
      resistance to ampicillin and nalidixic acid, 8.6% to streptomycin and 4.1% to
      chloramphenicol. Resistance to clinically relevant antimicrobials such as
      erythromycin, ciprofloxacin and tetracycline was 6.7, 12, and 15% respectively
      for all food isolates and was similar to corresponding resistance prevalences
      observed for human isolates, where 6.4, 12 and 13% respectively were found to be
      resistant. Comparisons of C. jejuni isolates in each location showed a high
      degree of similarity although some regional variations did exist. Comparison of
      total C. jejuni and C. coli populations showed minor differences, with C. jejuni
      isolates more resistant to ampicillin and ceftiofur. Multidrug resistance
      patterns showed some profiles common to human and clinical isolates.

PMID- 16623988
TI  - Interactions of viral pathogens on hospital admissions for pneumonia, croup and
      chronic obstructive pulmonary diseases: results of a multivariate time-series
      analysis.
AB  - Co-circulation of respiratory syncytial virus (RSV) and influenza has made the
      partitioning of morbidity and mortality from each virus difficult. Given the
      interaction between chronic obstructive lung disease (COPD) and pneumonia, often
      one can be mistaken for the other. Multivariate time-series methodology was
      applied to examine the impact of RSV and influenza on hospital admissions for
      bronchiolitis, pneumonia, and COPD. The Granger Causality Test, used to determine
      the causal relationship among series, showed that COPD and pneumonia are not
      influenced by RSV (P=0.2999 and 0.7725), but RSV does influence bronchiolitis
      (P=0.0001). Influenza was found to influence COPD, pneumonia, and bronchiolitis
      (P<0.0001). The use of multivariate time series and Granger causality applied to
      epidemiological data clearly illustrates the significant contribution of
      influenza and RSV to morbidity in the population.

PMID- 16623989
TI  - Impact of immigration and HIV infection on tuberculosis incidence in an area of
      low tuberculosis prevalence.
AB  - The aim of this study is to assess the effects of immigration from countries with
      a high prevalence of tuberculosis (HPCs), of HIV/AIDS prevalence, and the ageing
      of the indigenous population, on tuberculosis distribution in a low-prevalence
      area (LPCs), the Piedmont Region of Italy. Tuberculosis incidence and HIV cases
      were identified by linking records from the surveillance systems. Overall, 640
      tuberculosis cases were identified and crude annual incidence was found to be
      17.3/100000. The incidence rate ratio for HIV infection as a risk factor for
      tuberculosis (11.4 and 51.9 among individuals from HPCs and LPCs respectively)
      was greater than that for immigration from HPCs (6.7 and 30.9 among HIV+ and HIV-
      individuals). Immigration accounted for a larger number of incident cases
      [population attributable risk % (PAR %): 31.8 and 52.8% among HIV+ and HIV-
      individuals] than did HIV infection (PAR %: 5.4 and 11.1% among individuals from
      HPCs and LPCs). Efforts should be made to identify and treat young immigrants
      from HPCs.

PMID- 16623990
TI  - Risk factors for hospital-acquired methicillin-resistant Staphylococcus aureus
      bacteraemia: a case-control study.
AB  - A case-control study was undertaken in an acute district general hospital to
      identify risk factors for hospital-acquired bacteraemia caused by methicillin
      resistant Staphylococcus aureus (MRSA). Cases of hospital-acquired MRSA
      bacteraemia were defined as consecutive patients from whom MRSA was isolated from
      a blood sample taken on the third or subsequent day after admission. Controls
      were randomly selected from patients admitted to the hospital over the same time
      period with a length of stay of more than 2 days who did not have bacteraemia.
      Data on 42 of the 46 cases of hospital-acquired bacteraemia and 90 of the 92
      controls were available for analysis. There were no significant differences in
      the age or sex of cases and controls. After adjusting for confounding factors,
      insertion of a central line [adjusted odds ratio (aOR) 35.3, 95% confidence
      interval (CI) 3.8-325.5] or urinary catheter (aOR 37.1, 95% CI 7.1-193.2) during
      the admission, and surgical site infection (aOR 4.3, 95% CI 1.2-14.6) all
      remained independent risk factors for MRSA bacteraemia. The adjusted population
      attributable fraction, showed that 51% of hospital-acquired MRSA bacteraemia
      cases were attributable to a urinary catheter, 39% to a central line, and 16% to
      a surgical site infection. In the United Kingdom, measures to reduce the
      incidence of hospital-acquired MRSA bacteraemia in acute general hospitals should
      focus on improving infection control procedures for the insertion and, most
      importantly, care of central lines and urinary catheters.

PMID- 16623991
TI  - Re: "Can syndromic surveillance data detect local outbreaks of communicable
      disease?".

PMID- 16623993
TI  - [Correct awareness is needed for lead poisoning in children].

PMID- 16623992
TI  - Epidemic cholera in urban Zambia: hand soap and dried fish as protective factors.
AB  - Between 28 November 2003 and 23 February 2004, 4343 cases and 154 deaths from
      cholera (case-fatality rate 3.5%) were reported in Lusaka, Zambia. A case-control
      study was conducted in February 2004 to assess potential transmission routes and
      prevention strategies. Consumption of raw vegetables was significantly associated
      with cholera [adjusted odds ratio (aOR) 4.7, 95% confidence interval (CI) 1.7-13,
      P=0.003). Consumption of a local sardine-like fish was protective (aOR 0.3, 95%
      CI 0.1-0.7, P=0.008). Hand soap was present in 90% of control homes and 58% of
      case homes. Observed hand soap was a strongly protective factor (aOR 0.1, 95% CI
      0.04-0.4, P=0.001). No water source or treatment practice was significantly
      associated with cholera. This study documents the importance of foodborne
      transmission of cholera, illustrates the protective role of hand washing in an
      epidemic setting, and identifies a novel possible protective factor, a local
      fish, which warrants further research.

PMID- 16623994
TI  - [Effects of vitamin A nutritional status on the immune functions in young infants
      -reflection of relationship between nutrition and immunity in childhood].

PMID- 16623996
TI  - [Vitamin B12 nutritional status in preschool children in Chongqing].
AB  - OBJECTIVE: To explore the levels of serum vitamin B(12) (VB(12)) in preschool
      children, determine the relationship between the levels of serum VB(12) and
      anemia, and analyze the effects of several factors related to the level of serum
      VB(12). METHODS: From March 2005 to July 2005, the weight, height and complete
      blood count (CBC) were studied in 351 children aged 2 to 7 years from 4
      kindergartens of Chongqing. The concentrations of serum VB(12) and the dietary
      survey of 177 of the children were evaluated. RESULTS: The average level of serum
      VB(12) for the preschool children was 552 pg/ml. The levels of serum VB(12) in
      4.5% (8/177) of the children were below 200 pg/ml (defined as VB(12) deficiency),
      in 10.7% (19/177) of the children were 200 - 300 pg/ml (called marginal
      deficiency). There were no significant differences in the levels of serum VB(12)
      between boys and girls. And there was no correlation between the levels of serum
      VB(12) and hemoglobin. The results of multivariate stepwise regression analysis
      showed that the concentrations of serum VB(12) were mainly influenced by the
      contents of VB(12) in the foods (P = 0.03). Eight of the children with normal
      growth and development were diagnosed as VB(12) deficiency, only one of them was
      diagnosed microcytic hypochromatic anemia. The ranges of Hb, MCV and MHC were
      normal in the other 7 children. CONCLUSIONS: The levels of serum VB(12) of
      preschool children were higher than that of adults, suggesting that the levels of
      serum VB(12) change with age. There were no significant differences in the levels
      of serum VB(12) in 2-7 years old children between sex and ages. The levels of
      serum VB(12) were not correlated with the concentrations of hemoglobin.
      Macrocytic anemia may not occur in preschool children with VB(12) deficiency. The
      intake of VB(12) from the diets was one of the important factors for preschool
      children to keep the normal ranges of serum VB(12). It is beneficial for children
      to consume foods enriched with VB(12) to keep the normal level of serum VB(12).

PMID- 16623997
TI  - [Effect of zinc deficiency on the protein expression of vitamin D receptor and
      calcium binding protein in growth-stage rats duodenal mucosa].
AB  - OBJECTIVE: To study the effect of zinc deficiency on the protein expression of
      vitamin D receptor (VDR) and calcium binding protein (CaBP) in growth-term rats
      duodenal mucosa and to clarify the mechanism of zinc deficiency affecting the
      calcium absorption by gene transcription. METHODS: Thirty weaning male rats were
      randomly divided into three groups: zinc deficiency (ZD), paired-fed (PF) and
      zinc adequation (ZA). The ZA group received a diet containing 29.5 microg/g diet
      ad libitum; the ZD group received a diet containing less than 0.4 microg zinc/g
      diet ad libitum. To eliminate the effect of zinc deficiency on appetite, the PF
      group received a zinc-adequate diet restricted to the quantity of food consumed
      the previous day by the ZD rats. After 15 days feeding, duodenal mucosa was taken
      to measure expression of the protein of VDR and of CaBP by immunohistochemistry
      and Western-blotting. RESULTS: Immunohistochemistry demonstrated that the
      intestinal mucosal expression of both VDR protein and CaBP protein in ZD rats
      significantly decreased. Analysis of the photographs showed that the number of
      cells expressed VDR protein in ZD rats was significantly less than that of the PF
      and ZA rats (P < 0.001). The number of cells which expressed VDR protein in ZD,
      PF, and ZA groups was 52, 162, and 220, and the number of cells which expressed
      CaBP protein was 169, 240 and 280 (F = 132 and 22, P < 0.001). Western-blotting
      showed similar results. CONCLUSIONS: Zinc deficiency, by changing the activity of
      VDR, changes the protein expression of VDR, and thus affects the transcription of
      the target gene CaBP, resulting in the absorption of calcium that causes allo
      osteogenesis.

PMID- 16623998
TI  - [Effects of early intervention on learning and memory in young rats of marginal
      vitamin A deficiency and it's mechanism].
AB  - OBJECTIVE: In recent years, some experiments on vitamin A-deprived animals reveal
      a progressive and ultimately profound impairment of hippocampal CA1 area's long
      term potentiation and these losses are fully reversible by dietary vitamin A
      replenishment in vivo. Our previous study revealed that marginal vitamin A
      deficiency (MVAD) beginning from embryonic period impairs learning, memory and
      long-term potentiation (LTP) in young rats. But the losses might not be
      reversible if the vitamin A supplementation is late, especially when the critical
      period of hippocampus development is missed. The present study aimed to observe
      the recovery of learning and memory in vitamin A marginally deficient young rats
      after early intervention with vitamin A supplementation and begin to study the
      mechanism. METHODS: Rats were divided into control, MVAD, vitamin A intervention
      1 (VAI1) and VAI2 groups in this study. In control group (10 young rats) the dams
      and pups were fed with normal diet (VA 6500 U/kg). In MVAD group (19 young rats)
      the dams and pups were fed with MVAD diet (VA 400 U/kg). In VAI1 group (10 young
      rats) the dams were fed with MVAD diet till day 14 of pregnancy, then were fed
      with normal diet and the pups were fed with normal diet. In VAI2 group (13 young
      rats) the dams were fed with MVAD diet till delivery, then were fed with normal
      diet and the pups were fed with normal diet too. All the young rats were killed
      at the age of 7 weeks. During the last week of the experiment, the shuttle box
      active avoidance reaction tests were carried out. At week 7, the hippocampal CA1
      LTP was detected by electrophysiological technique. The expression of RAR-alpha,
      RAR-beta, RXR-beta, RXR-gamma, RC3 and tTG mRNA was detected by using semi
      quantified RT-PCR in hippocampus. RESULTS: (1) The times to reach the learning
      standard in MVAD group (45.6 +/- 12.1) were more than those in control group
      (17.1 +/- 4.4) (P < 0.01), in both VAI1 group (20.8 +/- 3.1) and VAI2 group (22.1
      +/- 4.0) were more than those in group MVAD (P < 0.01), and there were no
      significant differences among groups VAI1, VAI2 and control (P > 0.05) in active
      avoidance reaction tests. (2) The changes of field excitatory postsynaptic
      potentials (fEPSP) slope for MVAD group [(22.9 +/- 9.4)%] and VAI2 group [(39.1
      +/- 4.33)%] were less than that of control group [(57.5 +/- 27.3)%], respectively
      (P < 0.05). No significant difference was found between VAI1 and control group (P
      > 0.05). (3) The expression of RAR-beta and RXR-beta mRNA decreased by 48.72% and
      37.84% respectively (P < 0.05) compared with control, but the expression of RAR
      beta mRNA in group VAI1 was higher than that in group MVAD (P = 0.065). The
      expression of RC3 mRNA in MVAD group was lower than that in control (P = 0.061)
      and RAR-alpha mRNA in MVAD group was higher than that in control (P = 0.061). The
      expression of RXR-gamma and tTG mRNA had no significant difference among
      different groups as determined with semi-quantified RT-PCR in hippocampus.
      CONCLUSION: Early vitamin A intervention may make the impaired learning and
      memory behavior due to marginal vitamin A deficiency recover to the normal level
      in young rats, but lip losses in group VAI2 might not be reversible. Vitamin A
      may modulate the expression of RC3 mRNA by affecting RAR-alpha, RAR-beta and RXR
      beta to influence the LTP, learning and memory.

PMID- 16623999
TI  - [Childhood sexual abuses among 1307 adult students and analysis on results of
      Symptom Checklist-90 test].
AB  - OBJECTIVE: To survey the occurrence of childhood sexual abuses (CSA) among adult
      students and analyze the correlation between the sexual abuses and the results of
      Symptom Check-List-90 (SCL-90) test. METHODS: Questionnaire survey of 1307 adult
      students (701 female students, 606 male students) in a college about their
      personal experience on childhood sexual abuses. The surveys were conducted
      anonymously. And SCL-90 test was carried out at the same time. RESULTS: A total
      of 1307 students were surveyed. 18.67% of them (female students, 155, 22.11%;
      male students, 89, 14.69%) experienced non-physical contact sexual abuses and/or
      physical contact sexual abuses before the age of 18 years, among whom 124
      students (female students, 81, 11.55%; male students, 44, 7.26%) experienced
      physical contact sexual abuses, including 35 (26 female; 9 male) who suffered
      attempted genital or anal sexual intercourse and 11 (8 female and 3 male) were
      forced for genital or anal sexual intercourse; 13.70% (female 15.66%; male
      11.44%) said they experienced sexual abuses before the age of 16 years. Of the
      boys, experienced sexual abuse 54.7% from age 12 to age 16 years. And among the
      girls sexual abuses tended to increase with their growth (results of tendency
      test: chi(2) = 33.5, P < 0.001). The abusers were mostly males; only a small
      percentage of them used violence; for most female students who experienced non
      physical contact sexual abuses, the abusers were strangers (78.7%), while 71.3%
      of physical contact abuses were from acquaintances, 12.5% of them were teachers,
      17.5% were neighbors and 21.3% were relatives. Of the male victims, 89.9% said
      they knew the abusers before the abuses happened, 14.6% (13 out of 89) of them
      were teachers, and neighbors constituted another 21.3% (19 out of 89). Students
      who experienced childhood sexual abuses got higher scores than the students who
      didn't have such experience in the nine basic symptom factors of SCL-90 and
      higher than normal model of national young group notably. CONCLUSION: Childhood
      sexual abuse among students is not rare. The female students' incidence was
      obviously higher than that among the male students (chi(2) = 11.8, P = 0.001).
      About half of the abusers were the victims' close relatives, neighbors and
      teachers who live or study together with them. Personal experience of childhood
      sexual abuses may be one of the important factors influencing the victims'
      results of SCL-90 test.

PMID- 16624000
TI  - [A retrospective survey of childhood corporal punishment by school teachers in
      students].
AB  - OBJECTIVE: To ascertain the prevalence of childhood corporal punishment by
      teachers in students, to explore the influencing factors and associations between
      childhood corporal punishment and psychological problems. METHODS: Five hundred
      and twenty-eight students from a college and a technical secondary school in
      Hebei province were surveyed by self-administered questionnaire anonymously in
      Dec. 2004. The questionnaire used for this survey mainly included (1) general
      demographic information; (2) 5 forms of childhood corporal punishments, in this
      study, cases of teachers' corporal punishments were defined as those who answered
      positively one or more of the 5 questions relating to childhood corporal
      punishment by school teachers occurring before the age of 16 years; (3) Symptom
      Checklist-90 (SCL-90); (4) Youth Risk Behaviours. RESULTS: Overall, 57.6% of
      students reported having been corporally punished at least one time, one of four
      forms of corporal punishment by teachers before age of 16 years, the four forms
      corporal punishment were non-contact corporal punishment, e.g., running for
      punishment, repeat-doing homework many times for punishment, standing for
      punishment, kneel down for punishment, not allowing to eat, sending outside in
      winter, etc. (53.4%), hitting/kicking/pushing very hard with open
      hands/fist/feet/other part of body (16.1%), beating with an object (10.2%), and
      locking in a small compartment/tying with rope (0.2%). No students reported
      having been choked, or burned/scalded, or stabbed with a sharp object by the
      teachers. Males had a significantly higher overall prevalence rate than females
      (66.4% vs. 46.6%, chi(2) = 21.01, P = 0.000). There was no statistically
      significant association between a history of childhood corporal punishment and
      the three other demographic indicators, which included residence region (rural
      and non-rural area) prior to 16 years of age, parental education level, and
      whether the respondent lived in a single or multiple children family. Compared
      with their peers who had not experienced childhood corporal punishment by
      teachers, the students with two or more forms of corporal punishments by teachers
      showed significantly higher scores (punished group vs. unpunished group) of
      psychological symptoms of somatization (0.78 vs. 0.42), obsessiveness (1.22 vs.
      0.98), interpersonal sensitivity (1.24 vs. 0.89), depression (1.06 vs. 0.76),
      anxiety (0.90 vs. 0.64), hostility (1.11 vs. 0.68), paranoid ideation (1.11 vs.
      0.71) and psychoticism (0.84 vs. 0.56), and showed significantly higher rates in
      sadness (54.7% vs. 26.3%), drunk (37.2% vs. 20.1%), involving in physical
      fighting (15.1% vs. 3.6%) in the past year and current smoking (36.0% vs. 14.5%).
      CONCLUSIONS: The problem of corporal punishment by teachers is common in schools,
      and the problem has a significant correlation with youth mental health problems.
      The results highlighted urgent needs to increase public awareness on children
      rights, creating learning-friendly environment in school.

PMID- 16624001
TI  - [Development of children's self-regulation competence and its relationship with
      behavioral problems].
AB  - OBJECTIVE: To study the development of self-regulation competence and its
      relationship with behavioral problems in Chinese children with the method of
      questionnaire assessment. METHODS: The subjects of the study consisted of 18 to
      36 months old toddlers and 3 to 6 years old children. Self-regulation competence
      in this study included effortful control and self-regulation development.
      Effortful control is the concept described in Rothbart theory. Attentional focus
      and inhibitory control were two components in effortful control, which mainly
      reflect the positive control of emotion and behavior. The Early Childhood
      Behavior Questionnaire (ECBQ) and Children's Behavior Questionnaire (CBQ) were
      adopted to assess the attentional focus and inhibitory control of effortful
      control and impulsivity in children at different ages. Achenbach's Children
      Behavioral Checklist was used to measure behavioral problems in three to five
      years old children. RESULTS: Totally 114 18 to 36 months old toddlers and 443 3
      to 6 years old children were enrolled in data analysis. (1) The internal
      consistency of attentional focus in ECBQ and CBQ, alpha (Cronbach) value was
      respectively 0.89 and 0.75. The internal consistency of inhibitory control, alpha
      value was respectively 0.84 and 0.78. The alpha value of self-regulation
      development was respectively 0.84 and 0.94. (2) In 18 to 36 months old toddlers,
      there was no significant difference between genders in effortful control and self
      regulation development. In 3 to 6 years old children, the score of girls'
      effortful control was higher than the score of boys' effortful control, the
      scores of girls' self-regulation development factor except regulation motion were
      significantly higher than boys (t = 4.27 and 11.14, P < 0.05 or P < 0.01). (3)
      The self-regulation competence including attentional focus, inhibitory control
      and all the factors in self-regulation development was significantly higher with
      age in three to six years old children (F = 2.9-10.16, P < 0.05 or P < 0.01).
      Children in this period already had some regulation skills. The development of
      regulation competence and regulation skill was not on the same step. Some were
      fast and some were slow. (4) The scores of attention focus and inhibitory control
      had significantly positive correlation with the general score of self-regulation
      development, the coefficient of partial correlation analysis was 0.52 and 0.64,
      respectively (P < 0.001). (5) The impulsivity had no significant correlation with
      self-regulation competence in 18 to 36 months old toddlers. The scores of
      impulsivity and behavioral problems scores had significantly negative correlation
      with attentional focus, inhibitory control and self-regulation development in 3
      to-6 years old children. The coefficients were at low level, none was beyond 
      0.30 (P < 0.001). CONCLUSIONS: Effortful control or self-regulation had sex
      differences, girls had higher competence than boys, except motivation of self
      regulation. But such sex differences did not show significant difference in
      children younger than three years of age in this study. This phenomenon is
      consistent with the development of self-regulation reported by Kopp. Child self
      regulation competence increases with age. Generally speaking, the lower self
      regulation competent, the higher impulsivity and behavioral problems, but the
      correlation was at a low level. For assessment and prediction of occurrence of
      behavioral problems, self-regulation competence should be combined with the other
      influential factors.

PMID- 16624002
TI  - [Dehydroepiandrosterone sulfate and insulin of prepubertal girls born small for
      gestational age].
AB  - OBJECTIVES: To investigate whether the association between low birth weight and
      increased risk of developing premature adrenarche, adrenal hyperandrogenism,
      hyperinsulinism and insulin resistance is apparent in prepubertal girls born
      small for gestational age (SGA) and analyze when adrenarche occurs in SGA infants
      and normal birth weight girls. METHODS: The study was performed in 39 prepubertal
      SGA girls with a mean age of 7.4 +/- 1.7 years and 42 prepubertal appropriate for
      gestational age (AGA) girls with a mean age of 7.4 +/- 1.7 years served as
      controls. All children were born at term and were prepubertal. Detailed physical
      examination was performed for all the children after 12 h of overnight fasting.
      Blood samples were taken for the measurement of fasting glucose (FPG), insulin
      (FIns), dehydroepiandrosterone sulfate (DHEAS), cortisol and estradiol
      concentrations. Insulin sensitivity was assessed by insulin sensitivity index
      [IAI = log(e) (FPG x FIns)]. RESULT: There was no premature adrenarche in SGA and
      AGA groups. Birth weight was significantly lower in SGA group (P < 0.001).
      Gestational age was similar in both groups. At the time of the study, the ages,
      body mass index (BMI), fasting glucose, cortisol and estradiol did not
      significantly differ between the two groups. But body height and weight were
      significantly lower in the SGA group (P < 0.05 for both). The fasting plasma
      insulin in the SGA group was higher than that in AGA group (common logarithmic
      transformation: 1.076 +/- 0.041 vs. 1.050 +/- 0.051, P < 0.05). The insulin
      sensitivity index was not significantly different between the two groups (-4.0165
      +/- 0.1761 vs. -3.9768 +/- 0.2314). The serum DHEAS was significantly higher in
      SGA children than in AGA children (common logarithmic transformation: 2.637 +/-
      0.271 vs. 2.514 +/- 0.250, P < 0.05). From about age 7 the concentration of DHEAS
      had a gradual rise in AGA children. The time of DHEAS rise tended to be earlier
      in SGA children compared with AGA children. CONCLUSIONS: Adrenarche commences at
      approximately 7 years of age in AGA girls. The time of adrenarche tended to be
      earlier in SGA girls compared with AGA girls. There were adrenal hyperandrogenism
      and hyperinsulinism in prepubertal girls born small for gestational age. But
      there was no insulin resistance as assessed by insulin sensitivity index.

PMID- 16624003
TI  - [Disparity of asthma prevalence in Chinese schoolchildren is due to differences
      in lifestyle factors].
AB  - OBJECTIVE: To investigate the environmental lifestyle risk factors which may
      explain the disparity of asthma prevalence in the Chinese population. METHODS: In
      a cross-sectional study, 10 902 schoolchildren were recruited from Hong Kong (n =
      3110), Beijing (n = 4277), and Guangzhou (n = 3565) using the ISAAC Phase II
      protocol. The average age of the children among three cities was 10.1-10.4 years
      and 50%-53% were male. Each subject was given an ISAAC Phase II questionnaire to
      be completed by the parents or guardians. Random subgroups of at least 1000
      children from each city, added up to 3479 children underwent skin-prick testing.
      The sensitivity to eight common aeroallergens was assessed. Logistic regression
      analysis was used to determine the environmental and lifestyle risk factors for
      asthma and atopy. RESULTS: The prevalence of wheezing in the past 12 months (Hong
      Kong, 5.8%; Beijing, 3.8%; Guangzhou, 3.4%) was significantly higher in
      schoolchildren from Hong Kong than that from the Mainland of China (OR 1.64, 95%
      CI 1.35-1.99). Multivariate logistic regression analyses revealed that the use of
      gas cooking (OR 2.08, 95% CI 1.32-3.26), foam pillow (OR 1.94, 95% CI 1.19-3.16),
      and house dampness (OR 1.84, 95% CI 1.25-2.71) were significant risk factors for
      "current wheezing". The use of cotton quilt (OR 0.70, 95% CI 0.56-0.87), breast
      feeding (OR 0.79, 95% CI 0.66-0.96), and attendance of daycare (OR 0.73, 95% CI
      0.59-0.88) were protective factors against "current wheezing". When a summary
      measure of these variables was introduced into a regression model, the Mainland
      residency was no longer associated with "current asthma" or "current wheezing"
      suggesting that either these factors or other unmeasured factors associated with
      above factors are responsible for the lower prevalence of asthma in the Mainland
      of China. CONCLUSION: Several environmental and lifestyle factors represented
      characteristic of life in Mainland of China, including breast feeding, attendance
      of daycare, use of cotton quilt, use of pillow other than foam pillow, use of
      cooking fuel other than gas, and the absence of damp spots on the walls or
      ceiling, were the significant risk factors contributed to the disparity of asthma
      prevalence in children from Hong Kong and the Mainland of China.

PMID- 16624004
TI  - [Influence of Radix Astragali on nitric oxide and endothelin-1 in pulmonary
      tissue in hypoxemic pulmonary hypertension in rats].
AB  - OBJECTIVE: To study the influence of Radix Astragali (RA) on pulmonary tissue
      endothelin-1 (ET-1) and nitric oxide (NO) in hypoxic pulmonary hypertension rats.
      METHODS: Twenty one healthy male Wistar rats weighing 210-310 g were divided into
      three group at random with 7 in each. The rats in control group were raised in
      ordinary room condition; those in hypoxic group were raised in ordinary pressure
      hypoxic box [concentration of O(2) was (10.0 +/- 0.5)%] for 8 hours a day, for 30
      days; those in RA group were raised in the same condition as hypoxic group and
      treated with an intraperitoneal injection of RA 8 g/kg per day. The rats in the
      control group and hypoxic group were given the same volume of intraperitoneal
      injection of normal saline. Mean pulmonary arterial pressure (mPAP), mean carotid
      artery pressure (mCAP) were measured via right cardiac catheterization,
      concentration of NO in pulmonary tissue was measured by radioimmunoassay.
      RESULTS: (1) The mPAP (mm Hg) (21.9 +/- 1.6) and ET-1 (pg/ml) (309.1 +/- 58.1) in
      hypoxemic group were significantly higher than those in RA group (16.2 +/- 0.8,
      287.7 +/- 57.5) and control group (15.3 +/- 0.8, 241.1 +/- 52.5) (P < 0.01, <
      0.05), but the difference between RA group and control group was not significant.
      (2) NO (micromol/L) in pulmonary tissue in hypoxemic group (6.5 +/- 0.3) was
      lower than that in RA group and control group (9.2 +/- 0.9), NO in RA group was
      higher than that in hypoxic group but lower than that in control group (P <
      0.05). (3) There was no significant difference in mCAP among the three groups (P
      > 0.05). (4) Under electron microscope, the endothelial cells of arterioles of
      the lung tissue of control group were flat and had normal morphology. However, in
      the lung tissue of hypoxic group, there were proliferation, hypertrophy and
      swelling of endothelial cells of pulmonary medium and small arteries and plenty
      of mitochondria and endoplasmic reticula in cytoplasm. CONCLUSION: Chronic
      hypoxia can result in reconstruction and endothelial lesion in pulmonary
      arterioles of rats, elevation of mPAP and ET-1 in pulmonary tissue, and decrease
      of NO. Injection of Radix Astraglai can reverse the reconstruction of pulmonary
      vessels partially, regulate the concentration of ET-1 and NO in pulmonary tissue,
      which may have certain therapeutic effects on pulmonary arteriolar changes
      induced by hypoxia.

PMID- 16624005
TI  - [Effects of different doses of hydrocortisone on the disorder of coagulation in
      rats at early stage of septic shock].
AB  - OBJECTIVE: To investigate the effects of different doses of hydrocortisone (HC)
      on the disorder of coagulation in rats at early stage of septic shock. METHODS:
      The model of early septic shock accompanied by the disorder of coagulation in
      rats was set up by bolus injection of lipopolysaccharide (LPS) at 25 mg/kg
      through right femoral vein. Forty male Wistar rats were randomly divided into the
      following 5 groups: normal control (LPS and HC were substituted by same volume of
      normal saline solution), shock group (HC was substituted by same volume of normal
      saline), high-dose HC (HD group, HC 100 mg/kg), medium-dose HC (MD group, HC 50
      mg/kg) and low-dose HC (LD group, HC 5 mg/kg). Four hours after the HC treatment,
      the blood specimens were collected for the count of blood platelet (PLT), the
      activity of antithrombin III (ATIII), the content of D-dimer and von Willebrand
      factor (vWF). RESULTS: The count of PLT (x 10(9)/L) and the activities of ATIII
      (%) in shock group (586.00 +/- 71.179 and 50.600 +/- 19.248) were significantly
      lower than that in normal control group (1012.600 +/- 20.852 and 89.200 +/-
      12.109), and the level of D-dimer (microg/dl) and vWF (%) in LPS group (1.680 +/-
      0.999 and 7.288 +/- 0.652) as significantly higher than that in normal control
      group (0.66 +/- 0.772 and 3.656 +/- 1.407), P < 0.05. After HC treatment, the
      disorder of coagulation was attenuated to different degree. However, significant
      difference was found between HD, MD groups and shock group only in the count of
      PLT (P = 0.000), and there were no significant differences between HD, MD groups
      and shock group in the other three indices. Significant improvements were found
      in LD group (P < 0.05) in all the four indices and there were no significant
      differences between LD group and normal group in D-dimer and vWF. The effects of
      medium-dose HC was between LD and HD groups, and there were no significant
      differences between HD and MD group, P > 0.05. CONCLUSIONS: The results indicated
      that different doses of HC had different effects on coagulation in early stage of
      septic shock in rats. Low-dose HC may ameliorate the disorder of coagulation in
      early septic shock in rats. High-dose and medium-dose of HC had no significant
      improving effects on the disorder of coagulation.

PMID- 16624006
TI  - [Comparison between preschool and school children with obstructive sleep apnea
      syndrome].

PMID- 16624007
TI  - [Neonatal hyperthyroidism, report of 3 cases].

PMID- 16624008
TI  - [A case of hemorrhagic fever with renal syndrome].

PMID- 16624009
TI  - [Report of a case with Jackson-Lawler syndrome].

PMID- 16624010
TI  - [A case with neonatal MN group hemolytic anemia caused by IgG-type anti-M
      agglutinin].

PMID- 16624011
TI  - [Intermittent diarrhea and emaciation].

PMID- 16624012
TI  - [Newborn hearing screening in Hong Kong].

PMID- 16624013
TI  - [Differentiation of asthma from asthmatic bronchitis in children].

PMID- 16624014
TI  - [UDP-glucuronosyltransferase 1A1 gene and neonatal jaundice].

PMID- 16624015
TI  - [Summary of the 9th Asian Congress of Pediatric Nephrology].

PMID- 16624016
TI  - [Requirements for English abstracts of pediatric original articles (I)].

PMID- 16624017
TI  - [Strengthening awareness of and study of gastrointestinal functional disorders in
      children].

PMID- 16624018
TI  - [Gastric acid reflux and reflux esophagitis in children].
AB  - OBJECTIVE: To evaluate the significance of gastric acid reflux in children with
      reflux esophagitis (RE). METHODS: Twenty-four-hour esophageal pH monitoring and
      gastroscopy were performed in 180 children suffered from vomiting. The
      relationship between RE, non-esophagitis (NE), non-erosive reflux disease (NERD)
      and gastroesophageal reflux (GER) was analyzed. RESULTS: Sixty-five of the 180
      patients were confirmed as having RE by endoscopy. Among them, the number of
      cases with grades I, II and III RE according to the diagnostic criteria by
      endoscopy was 37, 19 and 9 cases, respectively, while the other 115 cases were
      diagnosed as NE. The positive rate of acid reflux in RE group was 58.5% (38/65),
      while it was 42.6% (49/115) in NE group (chi(2) = 4.179, P < 0.05). All
      parameters of acid reflux in RE group except for the episode of reflux and the
      number of reflux longer than 5 min were significantly higher than those in NE
      group. None of the parameters of acid reflux except for Boix-Ochoa score in grade
      III RE patients was significantly higher than that in both grade II and grade I
      RE cases. However, the difference in acid reflux parameter between grade I and
      grade II RE patients had not reached statistical significance. The results also
      showed that the positive rate of pathological acid reflux was 48.3% (87/180).
      Among them, 38 cases were RE, while other 49 cases were NERD. The difference in
      acid reflux between these two groups was not significant. CONCLUSIONS: Gastric
      acid reflux may play a major role in the development of RE in children, but may
      not be a sole pathogenic factor. The degree of acid reflux is not closely
      correspondent to the severity of RE. Acid reflux may not completely contribute to
      RE. Gastroscopy is very important for patients with reflux symptom.

PMID- 16624019
TI  - [Characteristics of anorectal motility spectrum and preliminary approach to
      treatment of functional constipation in children].
AB  - OBJECTIVE: To investigate the characteristics of anorectal motility spectrum in
      children with functional constipation in comparison with healthy children and
      determine the efficacy of treatment measures based on the results of anorectal
      manometry. METHODS: Anorectal manometric indexes were detected by the multi
      functional manometry in eight patients with functional constipation aged (11.4 +/
      4.8) yrs and ten healthy children aged (10.5 +/- 3.5) yrs from May 2004 to June
      2005. The patients received combined treatment including probiotics (Bifid.
      triple viable), prebiotics (Lactulose) and regular defecation according to the
      results of anorectal manometry in patients with functional constipation. The
      efficacy of these conservative measures were estimated during the course of
      treatment. RESULTS: No statistical differences were found in the indexes of
      effective length of anal sphincter, maximal systolic pressure and the duration of
      more than 50% of maximal systolic pressure between two groups. But minimal
      sensitivity and maximal tolerated volume between the two groups were
      significantly different. Seven of eight patients got better with the conservative
      treatment. CONCLUSION: Abnormal features exit in the anorectal motility spectrum
      of the children with functional constipation. The clinical efficacy of the
      conservative treatment measures based on the results of anorectal manometry is
      significantly good.

PMID- 16624020
TI  - [Application of double-balloon push enteroscopy in diagnosis of small bowel
      disease in children].
AB  - OBJECTIVE: Double-balloon enteroscopy is a new method that allows complete
      visualization of the lumen of small bowel. This study was conducted to evaluate
      safety, extent of observation and clinical efficacy of double-balloon push
      enteroscopy in diagnosis of patients with small bowel disease in children.
      METHODS: Fourteen cases suspected of small bowel diseases with negative findings
      on examinations with various routine diagnostic modalities underwent double
      balloon push enteroscopy from June, 2003 to May, 2005. Of the 14 cases, 13 had
      gastrointestinal bleeding and iron deficient anemia and 1 case had chronic
      diarrhea, the causes of these conditions were unknown. RESULTS: The enteroscopy
      reached jejunal-ileum transitional area, middle or lower portion of ileum and
      terminal ileum in 2, 10 and 2 cases, and the examination time was 40-50 min, 55
      70 min and 78-89 min, respectively. Lesions were detected in 12 of 14 the cases.
      The positive diagnostic rate was 85.7%. There were no relevant technical problems
      or severe complications. CONCLUSION: Double-balloon push enteroscopy is a safe,
      reliable diagnostic modality of high clinical value for small bowel diseases in
      children.

PMID- 16624022
TI  - [Diagnosis and treatment protocol for gastroesophageal reflux disease in
      children].

PMID- 16624021
TI  - [Correlation of intestinal mucosal injury with serum diamine oxidase].
AB  - OBJECTIVE: To study the relationship between the changes of intestinal mucosal
      tumor necrosis factor alpha (TNF-alpha), plasma diamine oxidase (DAO) values and
      the degree of mucosal injuries in young rat model of colitis and thereby to
      explore if plasma DAO could be used as a potential index for monitoring
      intestinal mucosal injury. METHODS: One hundred and four healthy young male
      Sprague-Dawley (SD) rats aged 5-6 weeks were randomly divided into three groups:
      zero time group (n = 8), model group (n = 48) and control group (n = 48). The
      model and control groups were further divided into 24 h, 72 h, 1 week, 2 weeks, 3
      weeks and 4 weeks subgroups, respectively, with 8 rats in each. The rats in model
      group were given 2, 4, 6-trinitrobenzene sulfonic acid (TNBSA) via enema to
      induce colitis, while the rats in the control group were given normal saline (NS)
      solution in the same way and those in zero time group were not treated. TNF-alpha
      and DAO were measured by immunohistochemical technique and spectrophotometry.
      RESULTS: The most serious enteric mucosal injury was seen 24 hours after giving
      TNBSA. Plasma DAO and TNF-alpha decreased as the intestinal mucosal injury was
      alleviated. CONCLUSIONS: Plasma DAO values may be used as a marker for intestinal
      mucosal injury. TNF-alpha is a factor for causing mucosal injury. Young rat
      colitis model can be used to study intestinal mucosal injury.

PMID- 16624023
TI  - [Summary of the First National Symposium on Pediatric Gastrointestinal Motility
      Disorders].

PMID- 16624025
TI  - [Clinical characteristics and long-term prognosis of Landau-Kleffner syndrome].
AB  - OBJECTIVE: To investigate the clinical and electroencephalographic (EEG)
      characteristics, therapeutic response and long-term prognosis of Landau Kleffner
      syndrome (LKS). METHODS: The clinical and EEG data of 10 children with LKS were
      analyzed, and therapeutic response and long-term outcome were followed up.
      RESULTS: The age of onset was from 2 to 10.5 years of age. All patients had
      acquired aphasia, characterized by verbal auditory agnosia. All patients had
      epileptic seizures. Partial motor seizures during sleep occurred in 8 patients,
      and other seizure type including atypical absence seizure and generalized tonic
      clonic seizure were also observed. Psychological and behavioral abnormalities
      occurred in 9 patients. There were no abnormalities of hearing and neuro-imaging
      tests in all patients, and family histories were negative. All the patients had
      EEG abnormalities. Focal spike and waves of temporal lobe were recorded in 9
      patients. Electrical status epilepticus during sleep (ESES) was observed on Video
      EEG (VEEG) monitoring in 4 patients. Anti-epileptic drugs (AEDs) showed favorable
      effects on epileptic seizures, but no effects on aphasia. All patients responded
      to corticosteroid, and got language improved. Eight patients were followed up for
      long-term outcome. All patients were seizure free, while the level of language
      development was abnormal in 5 patients. The VEEG follow-up was conducted in 6
      patients. Continuous epileptic discharges in slow sleep recurred in 2 patients
      after the discontinuation of steroid therapy. CONCLUSIONS: LKS is one of the
      childhood epileptic encephalopathy, and acquired aphasia and epileptic seizures
      are two main clinical characteristics. Aphasia is characterized by verbal
      auditory agnosia. Psychological and behavioral abnormalities are very common in
      children with LKS. Focal epileptic discharges were often located in temporal
      area, and usually generalized, and could be continuous during sleep. AEDs could
      control seizure but had no effects on aphasia. Early use of full dose
      corticosteroids could improve the language significantly. Long-term follow up
      showed that language impairments often remained, but the outcome in terms of EEG
      and epileptic seizure was good.

PMID- 16624024
TI  - [Effect of ketogenic diet on hippocampus synaptic reorganization and GluR5
      expression in kainic acid induced rat model of epilepsy].
AB  - OBJECTIVE: Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet.
      Its antiepileptic effect is certain but the underlying mechanism is unknown. The
      aim of the study was to reveal the possible mechanism from the view points of
      synaptic reorganization and GluR(5) expression in hippocampus. METHODS: Epilepsy
      was induced in Sprague-Dawley rats by kainic acid at postnatal day 28, all
      control animals were fed with normal rodent chow, whereas experimental rats were
      fed with ketogenic feed for 8 weeks. Spontaneous recurrent seizures were
      recorded. Mossy fiber sprouting and neuron damage in hippocampus were
      investigated by Timm staining and Nissl staining. Western blot and RT-PCR methods
      were applied to detect the expression of GluR(5) and GluR(5) mRNA in hippocampus.
      RESULTS: KD-fed rats (1.40 +/- 1.03) had significantly fewer spontaneous
      recurrent seizures than control diet-fed rats (7.36 +/- 3.75). The mean A of
      mossy fiber sprouting in the inner molecular layer of dentate gyrus was markedly
      higher in KA induced animals than that in saline control animals but it was
      similar in different diet fed groups. No significant differences were found in
      the mean A of Timm staining in CA(3) area and Nissl staining of neuron in hilus,
      CA(3) and CA(1) area. After KA kindling, KD-fed animals [(189.38 +/- 40.03)/mg
      pro] had significantly higher GluR(5) expression in hippocampus than control diet
      fed animals [(128.79 +/- 46.51)/mg pro] although their GluR(5) mRNA was the same.
      CONCLUSION: Mossy fiber sprouting may be responsible for epileptogenesis in KA
      induced model and KD can suppress seizures in these animals. KD may upregulate
      young rat GluR(5) in inhibitory interneurons of CA(1) thus lead to an increased
      inhibition to prevent the propagation of seizure.

PMID- 16624026
TI  - [Detection of a new mutation (1343-TT) in the iduronate-2-sulfatase gene from a
      Chinese patient with mucopolysaccharidosis type II].
AB  - OBJECTIVE: Mutations of the iduronate-2-sulfatase (IDS) gene is the ultimate
      cause of Hunter syndrome. Clarification of the nature of mutations will create a
      necessary premise for prenatal gene diagnosis. A mucopolysaccharidosis (MPS) type
      II patient and his parents from an ethnic minority in Yunnan province were
      studied to identify their possible mutation in IDS gene to establish the basis
      for prenatal gene diagnosis. METHODS: The patient was a boy, 6 years and 10
      months old. Urine glycosaminoglycans (GAGs) assay was used for preliminary
      diagnosis of the patient and his parents with the disease. The three related
      persons' DNA was extracted and the concentration and purity of the DNA were
      measured after the urine test results confirmed the diagnosis. Polymerase chain
      reaction-denaturing high performance liquid chromatography (PCR-DHPLC) analysis
      was performed to detect the position of the mutation around the hot spots of
      mutation in exon 9, 3, 8 of the IDS gene. DNA bidirectional direct sequencing was
      applied to analyze the mutation detected by PCR-DHPLC. RESULTS: The results of
      GAGs test showed that in the child with MPS, dermatan sulfate (DS) was positive
      (+++), heparan sulfate (HS) (+++), chondroitin sulfate (CS) and keratan sulfate
      (KS) were negative (-); while in his parents none of DS, HS, CS and KS was
      positive. Abnormal peaks in exon 9 of IDS gene shown by PCR-DHPLC were found in
      the patient. His mother had heterozygotic peaks. A new frame-mutation (1343-TT)
      in exon 9 of IDS gene of this patient was confirmed by DNA sequencing. The
      position where mutation occurred was inside codon 407 (TTT), that means two "T"
      deleted at position 1343 base pair (1343-TT) in cDNA of the IDS gene, caused a
      new frame-mutation. It caused elongation of the amino acid chain to a terminal
      codon TGA at position 429. Thus the peptide chain was shortened from 550 to 428
      amino acids. The patient is a hemizygote of the mutation and his mother is a
      heterozygote. CONCLUSION: A new frame-mutation (1343-TT) on the IDS gene was
      identified in this study. The patient is a hemizygote and his mother is a
      heterozygote. The mutation (1343-TT) resulted in loss of 122 amino acids, which
      probably caused seriously decreased enzyme activity of IDS, and the authors
      speculate that this mutation may be the pathological basis of the disease. So, if
      the mother becomes pregnant again, a prenatal gene diagnostic test for the same
      mutation should be performed. Furthermore, PCR-DHPLC followed by DNA sequencing
      are effective methods for diagnosis, including prenatal diagnosis of MPS II.

PMID- 16624027
TI  - [Serum resistin concentration and insulin resistance in obese children].
AB  - OBJECTIVE: Obesity is an important risk factor of insulin resistance and type 2
      diabetes. Adipocyte is a cell that can actively secrete a series of factors to
      regulate the pathway responsible for energy balance. Resistin is one of these
      factors. The purpose of this study was to investigate possible correlation
      between resistin and certain parameters, including body parameters and other
      parameters of glucose metabolism and roles of resistin in hyperinsulinemia or
      insulin resistance in obese children. METHODS: The serum resistin concentration
      was measured in 34 obese children (18 boys, 16 girls; age 8.9-15.9 years) and 31
      normal subjects (16 boys, 15 girls; age 7.8-14.5 years) by using ELISA.
      Anthropometric parameters, fasting glucose and insulin were measured in all
      subjects. Insulin resistance was assayed by homeostasis model assessment ratio
      (HOMA-R). Beta cell function was determined by using homeostasis model assessment
      beta cell (HOMA-beta). Correlation analysis was performed between resistin and
      other parameters. RESULTS: (1) The serum resistin concentration (common
      logarithmic transformation) was 3.1 +/- 0.5 in obese subjects and 2.7 +/- 0.8 in
      normal subjects. (P < 0.05). (2) The serum resistin concentration was not
      significantly correlated with sex, age, systolic and diastolic blood pressures,
      but was positively correlated with BMI, percent body fat (BF%), waist-hip ratio
      (WHR) (r = 0.299, r = 0.304, r = 0.322, P < 0.01); and positively correlated with
      fasting glucose, insulin, HOMA-R (r = 0.299, r = 0.303, r = 0.324, P < 0.05), but
      not significantly correlated with HOMA-beta. (3) Multiple linear regression
      analysis showed that only HOMA-R was the factor that significantly influenced
      resistin, R(2) = 0.105, the standard partial coefficient was 0.279 (P < 0.01).
      CONCLUSIONS: The serum resistin concentration in obese children were higher than
      that in normal children. The serum resistin concentration significantly
      correlated with the degree of obesity and the distribution of fat. Resistin is
      probably related to occurrence of hyperinsulinemia and/or insulin resistance in
      obese children.

PMID- 16624028
TI  - [Metformin hydrochloride ameliorates adiponectin levels and insulin sensitivity
      in adolescents with metabolic syndrome].
AB  - OBJECTIVES: Metabolic syndrome (MS) in adolescents was reported to be closely
      associated with cardiovascular diseases in adulthood. However, no unified
      treatment measure for MS in adolescents is currently available. The aim of this
      study was to measure the changes of serum adiponectin levels, insulin sensitivity
      and other biochemical markers after metformin therapy in adolescents with MS,
      which might provide some information for set up a unified therapeutic measure for
      MS in adolescents. METHODS: In this study, 348 moderately or severely obese
      adolescents and 24 non-obese healthy adolescents matched in age and sex were
      enrolled. The obese group included 208 males and 140 females aged from 7 to 16
      years (11.5 +/- 2.1 years). Oral glucose tolerance test and biochemical markers
      measurement were done to all these subjects. Whole body insulin sensitivity index
      (WBISI), homeostasis model assessment-insulin resistance (HOMA-IR) and fasting
      serum adiponectin were compared among 36 adolescents with MS (who had two or
      three abnormalities of hyperglycosemia, hypertension or dyslipidemia), 61 simple
      obese subjects without abnormality of biochemical markers and 24 healthy
      controls. Moreover, the changes of WBISI, HOMA-IR and adiponectin levels in 20
      cases with MS after metformin therapy for 3 months were measured. RESULTS: (1)
      HOMA-IR in control group (1.3), simple obese group (2.3) and MS group (4.9)
      increased by turns (F = 54.08, P < 0.001). WBISI and serum adiponectin in control
      group, simple obese group and MS group decreased by turns with significant
      difference [89.6, 22.8 and 10.7, F = 30.06; (7.1 +/- 2.6), (5.9 +/- 1.9), (2.8 +/
      0.9) mg/L, F = 64.93; P < 0.01 for all]. (2) HOMA-IR after metformin therapy
      decreased [5.7 (1.9-12.4) vs. 2.9 (0.9-7.4), t = 5.05, P < 0.01]; while the serum
      adiponectin levels increased with significant differences [(3.0 +/- 0.9) mg/L vs.
      (6.1 +/- 1.9) mg/L, t = 6.19, P < 0.01]. Systolic blood pressure [(132.4 +/- 7.5)
      mm Hg vs. (116.6 +/- 9.1) mm Hg, t = 8.36, P < 0.01], 2-hour glucose [(8.2 +/-
      2.9) mmol/L vs. (5.3 +/- 1.0) mmol/L, t = 3.96, P < 0.01], triglyceride [(2.8 +/-
      1.2) mmol/L vs. (1.3 +/- 0.9) mmol/L, t = 4.22, P < 0.01], total cholesterol
      [(4.9 +/- 0.6) mmol/L vs. (4.0 +/- 0.6) mmol/L, t = 4.72, P < 0.01], alanine
      aminotransferase [80.5 (29.0-286.0) U/L vs. 56.0 (23.0-163.0) U/L, t = 3.80, P <
      0.01]. CONCLUSION: Insulin sensitivity in adolescents with MS was lower than that
      of simple obese group. Metformin can improve or ameliorate adiponectin levels,
      insulin sensitivity and some clinical markers.

PMID- 16624029
TI  - [Mentality and behavior of children suffering from viral myocarditis].
AB  - OBJECTIVE: The present study was designed to investigate the influence of viral
      myocarditis on mental behavior of the children. METHODS: Mentality and behavior
      of the 178 children suffering from viral myocarditis were examined with Achenbach
      Child Behavior Checklist (CBCL) edited by Gong Yao-xian in 1986 and 104 sex, age,
      education and achievement-matched children with pneumonia or upper respiratory
      infection were enrolled as controls. RESULTS: The mentality and behavior of the
      children with viral myocarditis were distinctly abnormal. The abnormal rates of
      boys and girls suffering from acute and deferment viral myocarditis were
      evidently higher than those of control children (P < 0.01). The behavioral
      abnormalities of boys were hypochondria, social difficulties, unwell of body and
      attack. Whereas, the girls presented hypochondria, unwell of body, social flinch
      and disobeyed discipline, which was significantly different from the control
      children. The total and hypochondria cursory mark of the second check result of
      deferment boys were evidently higher than those of the first check (P < 0.05).
      The total cursory mark of the second check result of deferment girls was higher
      than that of the first check (P < 0.05) and evidently higher than that of the
      acute second check result (P < 0.01). The abnormal rates of mentality and
      behavior correlated positively with the age of children and they were associated
      with the severity of the illness. CONCLUSION: Viral myocarditis evidently
      affected the mentality and behavior of children, which should be paid great
      attention to.

PMID- 16624030
TI  - [Risk factors and treatment of hemorrhagic cystitis in children after
      hematopoietic stem cell transplantation].
AB  - OBJECTIVE: Hemorrhagic cystitis (HC) is one of the common complications of
      hematopoietic stem cell transplantation (HSCT), which causes significant pain,
      prolongs hospitalization, and occasionally results in renal failure and death.
      This study aimed at investigating the incidence, risk factors, and outcome of HC
      in children post umbilical cord blood transplantation (UCBT) and peripheral blood
      stem cell transplantation (PBSCT). METHODS: From October 1998 to June the
      clinical records of 53 pediatric patients (aged 2-18 years with median age of 7.5
      years) in our HCST center who underwent UCBT (n = 37) and PBSCT (n = 16) were
      retrospectively analyzed. Thirty out of 53 patients were diagnosed as hereditary
      hemolytic anemia (56.6%), and the others as haematological malignancies (43.4%):
      of whom 8 had acute lymphoblastic leukemia, 12 acute myeloid leukemia, 2 chronic
      myeloid leukemia and 1 non-hodgkin lymphoma. Conditioning regimen varied
      according to disease and clinical status, however based on cyclophosphamide (CTX,
      120-200 mg/kg) and busulphan (BU, 12-16 mg/kg) in the cohort. Total body
      irradiation (TBI) or total lymphoid irradiation was added in 7 patients
      respectively. The patients were divided into regular treatment group (RTG) with
      15 cases who received hyperhydration, alkalinizing, diuresis and Mesna during CTX
      infusion and prostaglandin E1 (PGE1) group (PEG) with 38 cases who received
      hyperhydration, alkalinizing, diuresis and Mesna plus prostaglandin E1 (0.03
      microg/kg.h). The risk factors of HC were examined by univariate and multivariate
      analysis. RESULTS: In all, 11 of the 53 transplanted patients developed HC (21%)
      with a median onset time of day +15 (rage day +2 - +25). HC was classified as
      early in 4 (36%) and late in 7 (64%), and scored as grade Iin 2 cases (18%),
      grade II in 4 (36%) and grade III in 5 (46%). There was no significant difference
      between RTG and PEG in the incidence of HC, however, the incidence was much
      higher in the group of patients who were > or = 6 years old, positive group of
      graft-versus-host disease (GVHD) and group of cytomegalovirus (CMV) infection
      than that in the group of patients who were < 6 years of age (32% vs. 8%, P <
      0.05), negative group of GVHD (35% vs. 7%, P < 0.05) and CMV non-infected group
      (62% vs. 13%, P < 0.05), respectively. Furthermore, by multivariate analysis, >
      or = 6 years old (OR = 3.53, P < 0.05) and CMV infection (OR = 4.31, P < 0.05)
      were significant risk factors for HC. Three of 11 patients were treated with
      bladder irrigation. All patients recovered from HC in a median 12.8 days (range 2
      53 days). CONCLUSION: Older age (> or = 6 years) as well as CMV infection were
      the risk factors of HC. Both hyperhydration and Mesna were effective in
      preventing HC, while addition of PGE1 could not reduce the incidence of HC. The
      prognosis of HC in children post HSCT was satisfactory.

PMID- 16624032
TI  - [Identification of Entero-shiga-like-toxin-producing and invasive Escherichia
      coli (ESIEC) from children with diarrheal disease].

PMID- 16624031
TI  - [Effects of hydrocortisone on circulating and intramyocardial inflammatory
      mediators in severe septic rats with myocardial injury induced by Escherichia
      coli].
AB  - OBJECTIVE: Severe sepsis and septic shock remain the most common cause of death
      in intensive care units. The main causes of death in sepsis are the cardiac
      dysfunction and hypotension resistant to cateolamines. The prevalence of relative
      adrenal insufficiency in severe sepsis and septic shock was estimated at about
      32%-51%. Several meta-analysis demonstrated that high-dose glucocorticoids
      decreased survival during sepsis, while stress doses of corticosteroids may
      benefit these patients. The exact reason for such widely divergent outcome
      produced by different doses of corticosteroid is still not understood. Therefore,
      the study was undertaken to observe the effects of different doses of
      hydrocortisone (HC) on circulating and intramyocardial inflammatory mediators in
      severe septic rats with myocardial injury induced by Escherichia coli (E. coli).
      METHODS: The model was established by two injections of inactivated E. coli Forty
      male Wistar rats were randomly divided into five groups: high-dose of HC group
      (150 mg/kg), medium-dose group (20 mg/kg), low-dose group (6 mg/kg), model group
      (NS substituted for HC), and control group (NS for E. coli and HC). Each group
      had eight rats. After 2 hours of treatment, specimens were collected to measure
      serum cardiac troponin I (cTnI), tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), nitric oxide (NO) and total NO synthase (NOS). NO
      and total NOS in myocardial homogenate were also detected. The expression of
      inducible NOS (iNOS) of myocytes was investigated. RESULTS: All the above
      mentioned markers in model group significantly higher than those in control
      group. After HC injection, serum cTnI concentrations in low-dose group decreased
      to normal values compared to that of model group, while in another two HC groups,
      the concentrations were higher than those in model group. TNF-alpha level was not
      significantly influenced. But IL-1beta level declined to normal values, being
      prominent in low-dose HC group. Neither high-dose nor middle-dose HC could lower
      serum NO or total NOS, but low-dose HC could greatly inhibit both NO and NOS
      levels (P < 0.05). There was no significant difference in the level of NO and
      total NOS of myocardial homogenate between left and right ventricles. There was
      no iNOS expression by normal myocardium, while the expression in model group was
      significantly increased. After HC injection, the iNOS expressions by myocardium
      in three HC groups were weaker than those in model group. The intensity of iNOS
      signals became weak with the decrease in HC dose. CONCLUSION: Different doses of
      HC might exert different effects on circulating and intramyocardial inflammatory
      mediators in severely septic rats with myocardial injury induced by E. coli. Low
      dose HC could significantly inhibit such mediators as well as iNOS expression by
      cardiomyocytes. The results suggest that low dose HC exert protective effect on
      myocardial injury of severely septic rats.

PMID- 16624033
TI  - [Expression of coxsackie-adenovirus receptor in hearts of mice with experimental
      viral myocarditis and its regulatory mechanism].

PMID- 16624034
TI  - [Investigation and analysis of the present state of antibiotics use in
      hospitalized children].

PMID- 16624035
TI  - [Magnetic resonance diagnosis of intracranial single inflammatory granulations in
      children].

PMID- 16624036
TI  - [Successful unrelated HLA-mis matched cord blood transplantation in pediatric
      patients with severe aplastic anemia].

PMID- 16624037
TI  - [Clinical study on spinal cord injury without radiologic abnormality in
      children].

PMID- 16624038
TI  - [Report of a case with multiple myositis ossificans progressiva].

PMID- 16624039
TI  - [A case of Russell-Silver syndrome].

PMID- 16624040
TI  - [A case with Coffin-Lowry syndrome].

PMID- 16624041
TI  - [Multisite multimodal treatment of children with attention-deficit hyperactivity
      disorder].

PMID- 16624042
TI  - [Comparative genomic hybridization and its applications in human medical
      genetics].

PMID- 16624043
TI  - [Immune-mediated pathogenesis and management of pediatric aplastic anemia].

PMID- 16624044
TI  - [Rasmussen encephalitis].

PMID- 16624045
TI  - [Requirements for English abstracts for original pediatric articles (II)].

PMID- 16624047
TI  - [Nasopharyngeal meningoencephalocele in a neonate].

PMID- 16624046
TI  - [Present status and prospects of development of neonatology in China].

PMID- 16624048
TI  - [Physiological maturity and early development of children].

PMID- 16624049
TI  - [Clinical study on improving the diagnostic criteria for neonatal asphyxia].
AB  - OBJECTIVE: Diagnosing neonatal asphyxia solely according to Apgar score may lead
      to misdiagnosis. The aim of this study was to explore new and more accurate
      diagnostic criteria for neonatal asphyxia. METHODS: Totally 10 376 live born
      neonates in our hospital were consecutively enrolled into the study. The
      following five items related to birth asphyxia, i.e., antepartum high-risk
      factors, Apgar scores, umbilical artery blood pH, organ injury, differential
      diagnosis on the causes of low Apgar score cases were examined and registered.
      The relationship among the first 4 items were analyzed. By differential
      diagnosis, the sensitivity and specificity of each index on diagnosing asphyxia
      and their complementary value on each other were investigated. RESULTS: The items
      correlated well with each other (P < 0.01 or < 0.05) but were not entirely
      parallel and consistent; they could complement but could not substitute for each
      other. The sensitivity of antepartum high-risk factors, low Apgar scores,
      umbilical artery blood pH < 7.00 and organ injury was 100%, 100%, 44.44% and
      100%, while the specificity was 17.99%, 98.90%, 96.05% and 96.62%, respectively.
      Of the 230 low Apgar score cases in this series only 50.9% coincided with
      asphyxia. For the 230 cases, when low Apgar score was combined with umbilical
      artery blood pH < 7.00, the sensitivity and specificity were 41% and 99.1% and
      when low Apgar score was combined with umbilical artery blood pH < 7.20, the
      sensitivity and specificity were 100% and 29.20%, respectively. After organ
      injury was added, the specificity was increased to 65.49%. When differential
      diagnosis was further added to exclude the other causes of low Apgar score cases,
      the misdiagnosis rate was minimized. CONCLUSION: Up to now, no single accurate
      index for diagnosing neonatal asphyxia is available. In order to increase
      diagnostic bases and reduce misdiagnosis, the criteria of sole Apgar score should
      be replaced by multi-index diagnostic criteria. Based on the present study, a set
      of integrated diagnostic criteria for neonatal asphyxia is proposed: (1) prenatal
      high-risk factors, (2) low Apgar scores (respiratory depression must present),
      (3) umbilical artery blood pH < 7.00, if only pH < 7.20, the items (2) (4) (5)
      must be present, (4) hypoxic-ischemic organ injury (at least one organ
      dysfunction), (5) the other causes of low Apgar scores should be excluded. The
      last 4 indexes should all be met and the first one serves as reference. If multi
      organ (three or more organs) dysfunction and (or) hypoxic-ischemic encephalopathy
      are present, severe asphyxia can be diagnosed.

PMID- 16624050
TI  - [Etiology of laryngeal stridor in neonates: analysis of 16 cases].
AB  - OBJECTIVE: To reduce misdiagnosis and explore etiology of laryngeal stridor in
      neonates. METHODS: Sixteen neonates with laryngeal stridor were reviewed. All the
      patients were examined with CT scan for larynx and lungs and some were examined
      with laryngoscopy. Laboratory examination and chromosome analysis were also done
      in all or some patients. RESULTS: All the 16 neonates were diagnosed before
      admission as congenital simple laryngeal stridor in other hospitals. Of the 16
      neonates with laryngeal stridor, 5 (31%) had thyroglossal ductal cyst, 1 (6%)
      neonate with cri du chat (5p(-)) syndrome, 2 (13%) neonates with Pierre-Robin
      syndrome and the rest 8 (50%) were suspected of congenital simple laryngeal
      stridor. CONCLUSION: Neonates with laryngeal stridor are easily misdiagnosed;
      neonatal thyroglossal duct cyst is one of common causes. The diagnosis for a
      congenital simple laryngeal stridor should be carefully made excluding the
      possibility of related diseases. The authors recommend that laryngoscopy and CT
      scan for larynx should be performed in the neonates with laryngeal stridor.

PMID- 16624051
TI  - [Optimal therapeutic window of hyperbaric oxygenation in neonatal rat with
      hypoxic-ischemic brain damage].
AB  - OBJECTIVE: Hyperbaric oxygenation (HBO) is an attractive procedure that has been
      used in treatment of hypoxic-ischemic encephalopathy (HIE). However, depending on
      the HBO protocol, especially the time point of starting treatment of HBO,
      different and conflicting results were obtained. This study was undertaken to
      search for the optimal therapeutic window of ABO in neonatal rat with hypoxic
      ischemic brain damage (HIBD). METHODS: Eighty-four healthy seven-day-old SD rats
      were used as research subjects and were randomly divided into seven groups with
      12 in each: sham group, HI group, HI (1 h) + HBO group (HBO starting 1 h after
      HI), HI (3 h) + HBO group (HBO starting 3 h after HI), HI (6 h) + HBO group (HBO
      starting 6 h after HI), HI (12 h) + HBO group (HBO starting 12 h after HI), HI
      (24 h) + HBO group (HBO starting 24 h after HI). Single HBO treatment (2.5
      atmospheres absolute, ATA for 1.5 h) was used in this study. Two indexes were
      used to assess the effect of HBO that included short-term (48 h after HI)
      histology change (the cell density in CA1 of hippocampus and cortex) and long
      term (5 w and 6 w after HI) neurobehavioral testing (grip test and treadmill test
      for evaluating the deficits of sensor motor; step-down avoidance test for
      assessing the deficits of memory). RESULTS: In HI (1 h) + HBO, HI (3 h) + HBO and
      HI (6 h) + HBO groups, neuron density of cortex and CA1 of hippocampus were
      1981.76 +/- 299.55, 1841.53 +/- 241.21, 1525.78 +/- 189.00 and 4430.56 +/-
      1180.31, 4507.54 +/- 1374.32, 3883.48 +/- 821.87, respectively, which were
      significantly higher than HIBD group (987.86 +/- 285.39 and 1813.59 +/- 295.33, P
      < 0.05, ANOVA). But in HI (12 h) + HBO and HI (24 h) + HBO, the neuron density of
      cortex and CA1 of hippocampus compared with those in HIBD group had no
      statistical significance (P > 0.05, ANOVA). In the sensor motor testing performed
      at 5 w after HI of rat, the grip time in grip test and the stay time in treadmill
      test of HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO groups were 193.39 +/-
      51.19, 168.39 +/- 34.02, 168.95 +/- 34.93 and 130.34 +/- 42.56, 128.20 +/- 27.69,
      125.74 +/- 36.99, respectively, which, compared with HIBD group, were
      significantly prolonged (P < 0.05, ANOVA). But in HI (12 h) + HBO and HI (24 h) +
      HBO groups, the time was not significantly longer compared with HI (P > 0.05,
      ANOVA). In the step-down avoidance test which was performed at 6 w after HI, the
      step-down latencies of HI (1 h) + HBO, HI (3 h) + HBO and HI (6 h) + HBO were
      96.91 +/- 29.91, 90.35 +/- 28.44 and 76.46 +/- 38.70, respectively, which were
      significantly prolonged (P < 0.05, ANOVA), but in HI (12 h) + HBO and HI (24 h) +
      HBO, the latencies did not significantly increase compared with HIBD, P > 0.05,
      ANOVA. CONCLUSIONS: The optimal therapeutic window of HBO in neonatal rat with
      HIBD was within the first 6 hours after HI. In this therapeutic window, HBO was
      highly effective in reducing the cell loss in CA1 of hippocampus and cortex.

PMID- 16624053
TI  - [Protective effects of allopurinol on white matter damage in premature rats].
AB  - OBJECTIVE: To investigate the protective effects of allopurinol (ALLO) on white
      matter damage in premature rats. METHODS: An animal model for white matter damage
      was established by bilateral carotid artery occulation (BCAO). Eighty-four
      newborn SD rats (1 day old) were used in this study and were divided randomly
      into three groups [sham surgery (Sham); BCAO group (BCAO); allopurinol-treated
      group (ALLO)]. Pathological changes were studied 7 days and 14 days after BCAO,
      respectively. Myelin basic protein (MBP) was detected by immunohistochemistry 7
      days and 14 days after BCAO, respectively. MBP-mRNA expression was determined 7
      days and 14 days after BCAO respectively by reverse transcription-polymerase
      chain reaction (RT-PCR) with fluorescent quantitative method. RESULTS: In BCAO
      group, mild or severe rarefaction was found in 10 cases in the corpus callosum
      area, especially at the cingulum. Pathological changes of white matter were found
      in 4 cases in internal capsule. Subcortex white matter rarefaction was found in 8
      cases. The extent of white matter rarefaction in ALLO group was reduced
      significantly. Enlargement of bilateral ventricles was found in 6 of 8 cases in
      BCAO group. The average ventricle size in ALLO group (2.44 +/- 0.71)% was reduced
      significantly as compared with that in BCAO group (3.27 +/- 0.73)% (P < 0.05).
      Strong MBP positive staining was found in sub-cortex, corpus callosum,
      hippocampus gyrus, and internal capsule of P14 sham surgery group. In BCAO group
      the MBP staining extent was reduced. The extent of MBP staining of ALLO group was
      between the other two groups. The optical density (OD) of MBP positive staining
      in BCAO group (6.60 +/- 0.68) was found higher than that in sham surgery group
      (9.40 +/- 0.53), the difference was statistically significant (P < 0.05).
      Compared with BCAO group, OD value in ALLO group (7.10 +/- 0.18) increased
      significantly (P < 0.05). RT-PCR data showed that MBP-mRNA copies (log10) in P7
      and P14 rats of both BCAO and ALLO groups were lower than that in sham surgery
      group (P < 0.01); However, MBP-mRNA copies in ALLO group were higher than that in
      BCAO group (P < 0.05). CONCLUSIONS: BCAO could be used in newborn rats (1 day
      old) to establish a premature white matter damage (WMD) animal model. Allopurinol
      may have a potential protective effect on premature SD rat with ischemic WMD.

PMID- 16624055
TI  - [Guidelines for management of premature infants].

PMID- 16624054
TI  - [2005 Forum for oxygen therapy in neonates and prevention and treatment of
      retinopathy of prematurity].

PMID- 16624057
TI  - [Role of sedation and analgesia in the pediatric intensive care unit].

PMID- 16624056
TI  - [Advancement of periventricular leukomalacia in the premature infant].

PMID- 16624058
TI  - [A meta-analysis on the effect of cyclophosphamide in treatment of nephrotic
      syndrome in children].

PMID- 16624059
TI  - [Human coronavirus-NL63 was detected in specimens from children with acute
      respiratory infection in Beijing, China].
AB  - OBJECTIVE: A new human coronavirus, HCoV-NL63, was identified recently from two
      Dutch children with acute respiratory infection (ARI) by two scientists in the
      Netherlands in 2004. To investigate if this newly discovered virus is associated
      with acute respiratory infections in pediatric patients in Beijing, tests were
      developed to detect HCoV-NL63 gene fragments from throat swab and nasopharyngeal
      aspirates collected from children in outpatient and inpatient departments with
      ARI in Beijing from Dec. 2003 to Mar. 2004. METHODS: A total of 245 clinical
      samples, which were negative either for diagnostic tests of human respiratory
      syncytial virus, influenza virus A and B, adenovirus, parainfluenza virus 1, 2
      and 3 by indirect immunofluorescence assay or human metapneumovirus by RT-PCR,
      were screened for HCoV-NL63 by nested PCR amplifying gene fragments located on
      the 1b and 1a genes. Amplicon of PCR from 1a gene of HCoV-NL63 was sequenced and
      the sequences were compared with those in GenBank nucleotide sequence database.
      RESULTS: Three (1.2%) out of the 245 samples were positive for HCoV-NL63 by
      nested-PCR using primers on 1b gene. These three samples also showed positive
      results on nested PCR in which primers were designed with sequences complementary
      to 1a gene segments. These positive samples were collected from hospitalized
      children under 2 years of age with pneumonia, bronchiolitis and bronchitis,
      respectively. The partial 1a gene sequences from two positive samples (BJ3140 and
      BJ3787) of HCoV-NL63 showed 100% homology between each other and high homology
      (98%-99%) with the sequences of 1a gene of HCoV-NL63 reported from different
      countries in GenBank. Phylogenetic analysis showed that BJ3140 and BJ3787 fell
      into the same genetic cluster (group 1). CONCLUSIONS: These data suggest that
      some of acute respiratory infections in young children in Beijing area are
      related to the newly identified HCoV-NL63.

PMID- 16624060
TI  - [Treatment of hemolytic uremic syndrome after acute stage].
AB  - OBJECTIVE: Hemolytic uremic syndrome (HUS) is a common primary disease that can
      cause acute renal failure in childhood. Renal disease is the most important long
      term complication in patients who survived the acute stage of HUS. Use of
      angiotensin-converting enzyme inhibitors (ACEI) and a restricted protein intake
      may be beneficial to the patients. However, it is not established whether such
      patients should be treated with steroids and immunosuppressors. The present study
      aimed to probe into the benefit of using steroid and immunosuppressor in patients
      after acute stage of HUS. METHODS: The subjects included 17 patients (aged 9
      months to 15 years, 12 males, 5 females) with HUS. Thirteen patients recovered
      from the acute stage of HUS, and underwent continuative treatment and follow-up.
      All the patients were treated with ACEI and early restriction of protein intake.
      Additionally, 2 children manifested as glomerulonephritis, one was treated with
      triperygium glycosides. Other 11 children who manifested as nephrotic syndrome
      were treated with prednisone, among them 5 children had no response or had
      incomplete response to prednisone, for these children short-term high dose
      cyclophosphamide or methylprednisolone pulse treatment were added; in 3 of the
      children short-term high dose methylprednisolone treatment was applied
      additionally for membranoproliferative glomerulonephritis and/or focal segmental
      glomerulosclerosis and crescentic glomerulonephritis. RESULTS: After follow-up
      for 2 months to 8 years, 4 patients with milder disease recovered, their blood
      pressure, renal function and urinalysis became normal, but 1 patient had
      recurrence. Among 9 patients with severe disease, 6 maintained normal blood
      pressure, recovered renal function and urinalysis, the other 3 patients failed to
      comply with treatment protocol and died during the 3rd, 9th and 13th month. The
      remainder (4 cases) gave up therapy and died on the 27th to 48th days of the
      course. CONCLUSION: The treatment applied in this study could improve the
      prognosis of patients after acute phase of HUS evidently by using the steroid and
      immuno suppressor according to clinical classification and pathological findings.
      It is recommended that triperygium glycosides is beneficial to children with
      glomerulonephritis, proteinuria and hematuria after acute stage of HUS.
      Adjustment of therapeutic schedule based on pathological findings after renal
      biopsy is helpful. To the patients with progressive renal failure who have no
      response to the steroid and immunosuppressors, steroid and immunosuppressor
      should be discontinued and dialysis treatment should be applied. Protocol
      compliance is also an important factor.

PMID- 16624061
TI  - [Clinical characteristics and speech therapy of lingua-apical articulation
      disorder].
AB  - OBJECTIVE: To explore the clinical characteristics and speech therapy of 62
      children with lingua-apical articulation disorder. METHODS: Peabody Picture
      Vocabulary Test (PPVT), Gesell development scales (Gesell), Wechsler Intelligence
      Scale for Preschool Children (WPPSI) and speech test were performed for 62
      children at the ages of 3 to 8 years with lingua-apical articulation disorder.
      PPVT was used to measure receptive vocabulary skills. GESELL and WPPSI were
      utilized to represent cognitive and non-verbal ability. The speech test was
      adopted to assess the speech development. The children received speech therapy
      and auxiliary oral-motor functional training once or twice a week. Firstly the
      target sound was identified according to the speech development milestone, then
      the method of speech localization was used to clarify the correct articulation
      placement and manner. It was needed to change food character and administer oral
      motor functional training for children with oral motor dysfunction. RESULTS: The
      62 cases with the apical articulation disorder were classified into four groups.
      The combined pattern of the articulation disorder was the most common (40 cases,
      64.5%), the next was apico-dental disorder (15 cases, 24.2%). The third was
      palatal disorder (4 cases, 6.5%) and the last one was the linguo-alveolar
      disorder (3 cases, 4.8%). The substitution errors of velar were the most common
      (95.2%), the next was omission errors (30.6%) and the last was absence of
      aspiration (12.9%). Oral motor dysfunction was found in some children with
      problems such as disordered joint movement of tongue and head, unstable jaw, weak
      tongue strength and poor coordination of tongue movement. Some children had
      feeding problems such as preference of eating soft food, keeping food in mouths,
      eating slowly, and poor chewing. After 5 to 18 times of therapy, the effective
      rate of speech therapy reached 82.3%. CONCLUSION: The lingua-apical articulation
      disorders can be classified into four groups. The combined pattern of the
      articulation errors is the most common one. Most of the apical sounds are
      replaced by velar sounds. The speech localization method is very useful in the
      therapy of apical articulation disorder. For children with feeding problems and
      oral motor dysfunction, it is needed to improve food texture and administer oral
      motor skill training.

PMID- 16624062
TI  - [Differentiation of human umbilical cord blood mesenchymal stem cells toward
      neurons induced by baicalin in vitro].
AB  - OBJECTIVE: To study the possibility and mechanism by which the human umbilical
      blood mesenchymal stem cells (MSCs) are induced to differentiate into neuron in
      vitro by baicalin, a kind of flavonoid isolated from an important medicinal plant
      Scutellariae Radix. METHODS: Human cord blood was obtained via sterile procedure
      with 20 U/ml of preservative-free heparin. MSCs were isolated by the two-step
      assay of gelatin sedimentation plus Ficoll centrifugation separation, purified
      and amplified in the liquid culture medium. According to the kind of
      antioxidants, the experiment was conducted in five groups: induction group,
      control group I, control group II, control group III and control group IV. Five
      subgroups of MSCs amplificated ex vivo for 2 weeks in each group were induced by
      the media containing baicalin (BC, 200 - 400 micromol/L) or baicalin-free for
      seven days. The media consisted of induction medium (DMEM plus 200 - 400
      micromol/L of baicalin) and post-induction medium (DMEM plus 200 - 400 micromol/L
      of baicalin, B27). The expression of neuronal or glia specific markers was
      evaluated by using indirect immunofluorescence cytochemistry staining. The
      percentage of differentiated cells and living cells was measured by Hoechest
      33,258 staining assay. RESULTS: After induction for 7 days, MSCs displayed
      neuronal morphologies, such as pyramidal cell bodies and processes formed
      extensive network. The undifferentiated cells did not exhibit a neuronal or glial
      phenotype, while the differentiating cells expressed NSE and MAP-2, the specific
      markers of neuron, but did not express GFAP, the specific marker of glia on the
      seventh day after induced by baicalin. The percentage of NSE and MAP-2 expressed
      on the seventh day after induced by baicalin was (76.3 +/- 9.2)% and (78.5 +/-
      5.5)%, respectively, which was significantly higher compared with control group
      I, control group II and control group III (P < 0.01), respectively. In addition,
      the ratio of living cells after induced for seven days in the BC group was (85.3
      +/- 4.8)%, which increased significantly compared with control group I, control
      group II and control group III (P < 0.01), respectively. CONCLUSIONS: Baicalin
      may induce the umbilical blood MSCs to neuron or neuron-alike cells in vitro in a
      moderate and stable manner. The mechanism of such an induction may be related
      with its controlling the activity of NF-kappaB which regulates the production of
      many kinds of cytokines, such as brain-derived neurotrophic factor (BDNF), etc.

PMID- 16624063
TI  - [Appendicitis complicated with intussusception in a neonate].

PMID- 16624064
TI  - [Results of unrelated umbilical cord blood stem cell transplantation for 65
      patients in China].
AB  - OBJECTIVE: From December 1998 to April 2004, 3960 umbilical cord blood units were
      stored in Guangzhou cord blood bank, which provided 100 umbilical cord blood
      units to 25 transplant center for 83 patients with malignant or non-malignant
      diseases. To study the related factors affecting unrelated umbilical cord blood
      stem cell transplantation, the authors analyzed retrospectively the results of
      transplantation of unrelated umbilical cord blood stem cells for 65 patients.
      METHODS: ALL (acute lymphocytic leukemia) cord blood units were obtained from
      full term normal vaginal and cesarean deliveries in Guangzhou Women and Infants
      Hospital. The fractionation, cryopreservation and thawing of the cord blood were
      performed according to the regulations of New York umbilical cord blood bank and
      pertinent literature. The selection of cord blood was based on HLA typing and the
      number of nucleated cells. The sex and HLA antigens of donors were defined as the
      evidence of engraftment. Time to engraftment was recorded when the absolute
      number of neutrophil ANC (absolute neutrophil count) was higher than 5.0 x 10(8)
      for three days. Event-free survival and graft versus host disease (GVHD) were
      provided by transplant centers. RESULTS: Out of 65 patients who received
      unrelated cord blood stem cell transplant, 49 patients were diagnosed as having
      malignant diseases [including 23 with ALL, 16 with AML (acute myeloid leukemia),
      7 with CML (chronic myelogenous leukemia), 3 with lymphoma and one with MDS
      (myelodysplastic syndrome)], 16 patients had non-malignant disease. The 65
      transplanted patients (42 male, 23 female) had a median age of 10 years (range 1 
      33 years) and a median body weight of 27 kg (range 10 - 67 kg). The patients
      received cord blood stem cells from unrelated 0-locus (n = 9) or 1-locus (n = 43)
      or 2-locus (n = 13) HLA mismatched donor. The median dose of infused cells was:
      total neutrophil count (TNC) 5.7 x 10(7), CD(34)(+) 5.1 x 10(5), CFU-GM 3.8 x
      10(4). Fifty of 65 (77%) patients had engraftment. GVHD occurred in 41 patients
      (63%), including acute grade I - II GVHD in 31 patients (76%), acute grade III -
      IV GVHD in 8 patients (20%) and chronic GVHD in 2 patients (5%). Fifty patients
      had engraftment (ANC > 5.0 x 10(8)) after a median time of 17 (range 7 to 44)
      days after transplant, while an autologous hematopoietic reconstitution was
      observed in 6 patients; 24 patients died of severe pneumonia (n = 8), acute GVHD
      (n = 4), or sepsis (n = 12) and the disease-free survival probability was 61%.
      CONCLUSIONS: Unrelated allogeneic umbilical cord blood transplantation may be a
      good substitution for unrelated allogeneic bone marrow transplantation with a
      good prospect.

PMID- 16624065
TI  - [Analysis of protein kinase C activity of peripheral blood T lymphocytes in
      children with acute idiopathic thrombocytopenic purpura].
AB  - OBJECTIVE: Acute idiopathic thrombocytopenic purpura (AITP) is a common
      autoimmune disease in children. Thrombocytes decrease extremely in serious
      patients, its pathogenesis involves abnormal activation of T lymphocytes and T
      cell-dependent production of autoantibody. The aim of the present study was to
      investigate changes of protein kinase C (PKC) activity in peripheral blood T
      lymphocytes in children with AITP and the relationships between PKC activity and
      T lymphocytes activation and thrombocytopenia. METHODS: Peripheral blood
      specimens were collected from children with acute ITP (n = 35) and healthy
      children (n = 30), and T lymphocytes were isolated and purified by using T cells
      Segregation Enrichment Column. PKC activity was detected by using PepTag Assay, a
      non-radioactive detection method. The reaction mixture, in a final volume of 25
      microl, consisted of 5 microl reaction buffer, PepTag C1 5 microl (0.4
      microg/microl), PKC activator solution (DG) 5 microl, peptide protection solution
      1 microl and sample 9 microl. Phosphorylation reaction was allowed to continue
      for 30 minutes, then 25 microl reaction mixture was subjected to electrophoresis
      on a 0.8% agarose gel at 100 V for about 20 minutes. After electrophoresis, the
      PepTag C1 peptides which were phosphorylated and non-phosphorylated were
      separated, phosphorylated PepTag C1 peptide with negative electricity migrated
      toward the anode (+), but nonphosphorylated PepTag C1 peptide with positive
      electricity migrated toward cathode (-), the gel was photographed.
      Electrophoresis bands on anode represented PKC activity and were analyzed
      quantitatively. FasL, which is T cell activation marker, was determined by flow
      cytometer and platelet was counted by cell counting meter. RESULTS: Compared with
      healthy children, children with AITP had significantly higher PKC total activity
      [(0.97 +/- 0.21) nmol/(min.ml) vs. (0.55 +/- 0.13) nmol/(min.ml), (P < 0.05)].
      Expression of FasL on T cell subpopulation in children with AITP was
      significantly higher [Th FasL: (32.7 +/- 3.4) vs. (14.7 +/- 4.2); Tc FasL: (17.3
      +/- 9.7) vs. (11.6 +/- 8.5)%, (P < 0.05)]. Besides, relationships between the
      changes of PKC activity, Th FasL and Tc FasL had positive correlation (r(1) =
      0.68, r(2) = 0.53, P < 0.05). However, PKC activity and platelet count had a
      significantly negative correlation (r = -0.75, P < 0.05). CONCLUSION: Increased
      PKC activity was seen in children with AITP, which can cause damage to
      thrombocytes and reduction of thrombocytes. PKC signal transduction pathway might
      play an important role in the immunopathogenesis of AITP.

PMID- 16624066
TI  - [Experimental study of the anti-tumor effect of arsenic trioxide or thalidomide
      alone and combination of both for treatment of myelodysplastic syndrome model].
AB  - OBJECTIVE: To investigate the anti-tumor effect and the possible mechanism of
      arsenic trioxide (ATO) alone or in combination with thalidomide (THAL) for
      treatment of SCID mice model transplanted with human myelodysplastic syndrome
      (MDS) cell line MUTZ-1 cells. METHODS: (1) The animal model was established in
      SCID mice; 75 SCID mice and 10 BALB/CA-nude mice were studied in this experiment.
      MUTZ-1 cells were cultured in vitro and made for mono-cell suspension (with 1 x
      10(8)/ml cell density and in exponential growth behavior) and were subcutaneously
      implanted into 4-6-week-old first-generation SCID mice and BALB/CA-nude mice. The
      biological characteristics of the subcutaneous tumor cells were evaluated by the
      methods of cell morphology, histopathology, immunology by flow cytometer,
      chromosome analysis and immunohistochemistry (IHC). Subsequently, the tumor cells
      from first-generation mice model were respectively subcutaneously implanted into
      61 second-generation SCID mice and 8 BALB/CA-nude mice and the rate of the tumor
      formation and the latent period of the tumor formation were observed. (2) In
      vivo, 56 MDS-SCID mice were randomly grouped; 40 of them were used as ATO treated
      groups [5.0 microg or 7.5 microg/(g.d) intraperitoneal injection (i p) 5 d a
      week, x 3 weeks] alone or in combination with THAL 8 microg/(g.d), x 3 week or
      THAL alone and 16 mice as the control groups [with 0.9% NaCl 10 microl/(g.d) i p
      or untreated]. The mean tumor diameters (MTD) of subcutaneous tumors were
      measured with slide gauge and the therapeutic effects and the survival period and
      the rates of survival were evaluated by the methods of histopathology, IHC,
      microvessel density count (MVD), DNA ladder, TUNEL and PI with flow cytometry.
      RESULTS: (1) The rate of the subcutaneous tumor formation was higher (98.4%,
      60/61) in SCID mice than in BALB/CA-nude mice (62.5%, 5/8) (P = 0.0027). The
      latent period of the tumor formation was significantly longer (23 - 28 d, median
      26 d) in BALB/CA-nude mice than that in SCID mice (10 - 17 d, median 12 d) (Z =
      4.605, P < 0.001). The biological characteristics of the tumor cells in the MDS
      SCID mice model were evaluated and considered as of anthropo-source and were
      consistent with that of MUTZ-1 cells, which showed that the MDS-SCID mice model
      was successfully established. (2) In vivo, the marked inhibitory effect on the
      subcutaneous tumors growth (F = 146.94, P = 0.000) and the higher rates of cells
      apoptosis were seen in the groups treated with ATO 5.0 microg or 7.5 microg alone
      or in combination with THAL than in control groups (F = 30.10, P = 0.000). The
      longer-survival periods (F = 25.11, P < 0.01) with lower toxicity were only
      observed in lower-dose group of ATO 5.0 microg than in other treated groups and
      control groups. THAL alone group had a mild inhibitory effect on the tumors
      growth (> 2 weeks) with a longer-survival period and higher-rate of survival than
      controls, but had no events of cell apoptosis. The expression of vascular
      endothelial growth factor (VEGF) protein and CD34 protein and MVD were markedly
      down-regulated by THAL compared with control groups (P < 0.01), suggesting that
      the possible mechanisms of the inhibitory effect on tumor growth by THAL related
      to inhibition of vascular endothelial growth. The legs paralysis in 2 MDS-SCID
      mice was observed after treatment with THAL alone (11 d and 15 d, respectively),
      which were considered as the side-effect of THAL associated with deep venous
      thrombotic (DVT) events and the mechanism for these events is unclear. The
      therapeutic effects were unsatisfied in the group treated with ATO 7.5 microg in
      combination with THAL due to more intense toxicity and the shorter-survival
      periods than other treated groups (P < 0.001). CONCLUSIONS: (1) The Hum-MDS-SCID
      mice model was successfully established, which served as an animal model for
      studying pathogenesis of MDS and therapeutic agents selection. (2) ATO had marked
      inhibitory effect on the subcutaneous tumors growth in MDS-SCID mice model in
      vivo. The longer-survival periods and higher-rates of survival with lower
      toxicity were observed in lower-dose ATO (5.0 microg) alone than other groups.
      The mechanisms of the anti-tumor effect of ATO were considered to be related to
      inducing cells apoptosis, but in the case of THAL, related to inhibition of
      vascular endothelial growth. (3) The results do not support the preconceived
      hypothesis of a synergistic effect of ATO (7.5 microg) in combination with THAL
      for treatment of MDS mice model due to the more intense toxicity and the shorter
      survival periods in the treated group. Whether or not this will translate into
      clinically relevant effect of the ATO or THAL in MDS patients deserves further
      investigation.

PMID- 16624067
TI  - [Detection of serum interleukin-15 in peripheral blood of patients with JIA and
      its clinical significance].

PMID- 16624068
TI  - [Successful treatment of a very low birth weight infant with a body weight of 625
      grams born at 28 weeks of gestational age].

PMID- 16624069
TI  - [Report of an infant died from hypertrophic cardiomyopathy accompany with ostium
      secundum atrial septal defects in early stage].

PMID- 16624070
TI  - [Congenital acute lymphocytic leukemia ALL-2 in a 9-hour old newborn infant].

PMID- 16624072
TI  - [The passionate pursuit of perfection].

PMID- 16624073
TI  - [Attention to arterial thrombotic diseases].

PMID- 16624074
TI  - [Focus on the application of new techniques in clinical diagnosis and treatment
      of intestinal diseases].

PMID- 16624076
TI  - [What can we learn from animals?].

PMID- 16624077
TI  - [Importance of clinical epidemiology and evidence-based medicine in basic
      training in internal medicine].

PMID- 16624079
TI  - [Clinical epidemiological characteristics of 3870 cases of colorectal cancers in
      Guangdong region].
AB  - OBJECTIVE: To explore the clinical characteristics and pattern of incidence of
      colorectal cancers in Guangdong region. METHODS: Analysis and summary were made
      for 3870 colorectal cancer patients pathologically confirmed in the Nanfang
      Hospital and Huizhou Municipal Central Hospital of Guangdong province. RESULTS:
      Median age of 3870 cases with colorectal cancer was 55.3. The high-risk age
      ranged from 41 to 70.204 cases among them were young patients (age < or = 30,
      5.3%). With increase of age the number of cases with rectal cancers decreased
      gradually, while cancers occurring in the right hemi colon increased gradually.
      The ratio between male and female was 1.42:1. There were altogether 3958 colonic
      cancer lesions found in all the cases. Among them 3783 (97.8%) cases presented
      with a single lesson, 87 (2.2%) cases presented with multiple lesions. 2243
      (56.7%) lesions located in the rectum, 717 (18.1%) in the left hemi colon, 998
      (25.2%) in the right hemi colon. Histological types in all the lesions cases were
      grouped as follows: tubular adenocarcinoma 2943 (76.0%); papillary adenocarcinoma
      256 (6.6%); mucinous carcinoma 425 (11.0%); and miscellaneous types 246 (6.4%).
      Colorectal cancers with poor differentiation occurring in the young were 38.2%
      while in the middle age and the elderly were 29.9% and 14.6%, respectively. The
      difference between two groups showed a statistical significance (P < 0.01). The
      cases with confirmed stage A, B, C and D were 234 (6.0%), 1936 (50.0%), 1310
      (33.9%) and 390 (10.1%), respectively, according to Dukes' staging system. The
      cases with the progressing stages (B, C, D stages) were 3636 (94.0%) among all
      the cases. CONCLUSIONS: The number of patients with colorectal cancer admitted in
      hospital increased gradually in the recent 20 years, and showed a trend with the
      decrease percentage in rectal cancer and the gradual increasing in right hemi
      colon cancer with increase of patients age. Half of the colorectal cancer
      occurred in the rectum, the rest occurred in the left and right hemi colon. The
      three clinical epidemiological characteristics of colorectal cancer, which once
      existed in Chinese, has disappeared in Guangdong region.

PMID- 16624080
TI  - [A study of extraesophageal presentations in gastroesophageal reflux disease].
AB  - OBJECTIVE: The aim of this prospective multi-center study was to evaluate the
      clinical characteristics of extraesophageal reflux disorders (EED) in
      gastroesophageal reflux disease (GERD) patients and the therapeutic effect of
      proton pump inhibitor (PPI) on EED. METHODS: We investigated GERD patients in 4
      hospitals in Shanghai in a same time period. These patients were diagnosed as
      GERD by finding reflux esophagitis (RE) on endoscopy or with abnormal reflux
      during 24 h esophageal pH monitoring. Typical GERD symptoms and EED symptoms were
      evaluated by questionnaire. Patients with EED symptoms underwent
      videolaryngoscopy and abnormalities were recorded. RESULTS: Totally 200 subjects
      were enrolled in this study. Among them 95 patients complained of EED. The RE
      cases were 134 in number and EED occurred in 65 of the RE patients. The commonest
      presenting symptom of EED was globus or foreign body feeling in the throat (27%),
      followed by cough, soar throat and hoarseness. Asthma was a rare symptom, the
      occurrence being 21%, 16%, 11% and 3% respectively. The rate of typical GERD
      symptoms existing in EED group was 56%. The severity of EED symptoms showed no
      significant difference between RE and NERD patients. Abnormalities were found in
      58% of subjects with EED on laryngoscopy, the occurrence of arytenoids medial
      wall erythema/edema was 25%, vocal cord erythema/edema was 32%, posterior
      pharyngeal wall cobble stoning was 20%, and 42% of the patients showed no
      abnormalities on laryngoscopy. Higher dosage PPI therapy showed effects on the
      relief of EED, and the relief rate was 95% after 8 weeks of treatment.
      CONCLUSIONS: Our results suggest that a significant part of GERD patients
      suffered from EED, and value of laryngoscopy and 24 h pH monitoring is limited
      for the diagnosis of EED. Higher dosage of PPI was effective for the treatment of
      EED.

PMID- 16624081
TI  - [The value of magnifying endoscopy combined with human telomerase reverse
      transcriptase in diagnosing precancerous gastric lesions].
AB  - OBJECTIVE: To explore the diagnostic value of magnifying endoscopy and human
      telomerase reverse transcriptase (hTERT) in identifying precancerous lesions of
      gastric mucosa. METHODS: 154 patients with upper digestive symptoms were included
      in the study. They were examined by the same senior doctor using magnifying
      endoscopy, and real-time diagnosis was made during the examination. Forceps
      biopsies were taken for pathological examination and were examined the expression
      of human telomerase reverse transcriptase mRNA (hTERT mRNA) by real-time
      quantitative PCR. The morphology of gastric pits under magnifying endoscopy was
      classified as follows: type A: round spot pits, type B: linear, type C: sparsely
      and thickly linear, typed D: patchy, and type E: villous. RESULTS: The divergence
      of intestinal metaplasia had significant differences implications among the
      gastric pit patterns from B to E under magnifying endoscopy (chi(2) = 17.58, P <
      0.05). The more sever the intestinal metaplasia, the higher the pattern scale of
      the gastric pit (Pearson = 0.531, P < 0.05). The degree of dysplasia had a
      parallel relationship with the gastric pit patterns changed from C to E (chi(2) =
      10.256, P < 0.05, Pearson = 0.549, P < 0.05). The expressions of hTERT mRNA of
      mucosa had significant differences among the gastric pit patterns B, C, D and E
      (F = 3.274, P < 0.05); If the expression of hTERT mRNA were taken as diagnostic
      criteria of gastric cancer, 65% of pit type E would be considered as gastric
      cancer which were otherwise negative by pathology. CONCLUSIONS: The micro
      structural changes of gastric mucosa under magnifying endoscopy can reflect the
      severity of gastric disease, hTERT is a very important marker for diagnosis of
      gastric carcinoma. It is useful to predict the malignant change of gastric
      precancerous lesions in patients by following up high expression of hTERT mRNA
      combined with pit type E diagnosed by magnifying endoscopy.

PMID- 16624082
TI  - [China coronary secondary prevention study: analysis of patients with different
      myocardial infarction history].
AB  - OBJECTIVE: To assess whether Xuezhikang was effective in the secondary prevention
      of coronary heart disease (CHD) for patients with different length of myocardial
      infarction (MI) history. METHODS: 2135 patients with MI history of 28 days to 3
      months and 2735 patients with MI history of 3 months to 60 months were recruited
      separately to receive treatment with Xuezhikang capsule or placebo. The primary
      end-points were nonfatal myocardial infarction and death from CHD. RESULTS: The
      occurrence of coronary events were found to be not statistically significantly
      different for the two groups of patients. For patients with MI history of 28 days
      to 3 months, Xuezhikang significantly reduced the risk of CHD events by 56.7% (P
      < 0.0001) and resulted in a 48.6% (P = 0.0002) risk reduction in all-cause
      mortality as compared with placebo. For patients with MI history of 3 months to
      60 months, Xuezhikang significantly decreased the risk of CHD events by 35.3% (P
      = 0.0008) and led to a 20.0% (P = 0.1181) risk reduction in the all-cause
      mortality as compared with placebo. Adverse effects and abnormal laboratory
      parameters did not differ significantly in the two groups of patients.
      CONCLUSIONS: Xuezhikang is more effective for patients with MI history of 28 days
      to 3 months as compared with patients with MI history of 3 months to 60 months.
      Patients with MI history should be treated with Xuezhikang early in order to
      achieve better prevention of CHD.

PMID- 16624083
TI  - [Efficiency and safety of carvedilol treatment in high risk hypertensive
      patients].
AB  - OBJECTIVE: To evaluate the efficiency and safety of carvedilol treatment in high
      risk hypertensive patients. METHODS: Carvedilol was administered in 379
      hypertensive patients with high risk factors such as NIDDM, lipid disorders or
      abnormal serum creatinine level and 364 primary hypertensive patients without
      risk factors. Before and after treatment with carvedilol, blood pressure, heart
      rate, serum glucose, lipid profile and serum creatinine level were tested.
      RESULTS: After treatment, the blood pressure and heart rate were reduced
      significantly and there was no difference between the two groups. After
      treatment, the serum glucose, TC, TG and LDL in the high risk group, were reduced
      from 6.13, 5.37, 2.29 mmol/L and 3.04 to 5.80, 5.11, 2.05 and 2.87 mmol/L
      respectively (P < 0.001). TC was also reduced in the primary hypertensive group
      after treatment from 4.73 mmol/L to 4.69 mmol/L (P < 0.01). The efficiency rate
      of treatment in the high risk group and the primary hypertensive group was 97.75%
      and 98.32%; there is no statistical difference. CONCLUSION: The efficiency and
      safety of carvedilol in the high risk hypertensive patients is same as in the
      primary hypertensive patients.

PMID- 16624084
TI  - [CD4+ CD25+ regulatory T cells suppress CD4+ T cell responses in patients with
      persistent hepatitis C virus infection].
AB  - OBJECTIVE: To study the role of CD(4)(+) CD(25)(+) regulatory T cells (CD(4)(+)
      CD(25)(+) Treg cells) in CD(4)(+) T cell responses in patients with persistent
      infection of hepatitis C viruses. METHODS: Flow cytometry was used to determine
      the number of CD(4)(+) CD(25)(+) Treg cells and intracellular cytokine production
      by CD(4)(+) CD(25)(+) Treg cells in patients with chronic HCV infection. To
      assess their regulatory properties CD(4)(+) CD(25)(+) Treg cells were co-cultured
      with CD(4)(+) CD(25)(-) T cells from patients or controls; the expressions of
      Foxp3 were measured by RT-PCR. RESULTS: CD(4)(+) CD(25)(+) Treg cells comprised
      (13.5 +/- 1.8)% of peripheral CD(4)(+) T cells in the blood of persistent
      hepatitis C virus infected patients, which was significantly higher than that of
      healthy controls (5.3 +/- 0.8)% (P = 0.004). CD(4)(+) CD(25)(+) Treg cells highly
      expressed Foxp3 and mainly synthesized IL-10; CD(4)(+) CD(25)(+) Treg cells
      dramatically suppressed the proliferation of CD(4)(+) T cells and the production
      of IFN gamma; the suppressive activity of CD(4)(+) CD(25)(+) Treg cells in
      patients with persistent HCV-infection was higher than that in healthy controls
      (P = 0.034). These effects were dose-dependent but IL-10 and transforming growth
      factor beta independent. CONCLUSION: Patients with persistent hepatitis C virus
      infection show an increased number and suppressive activity of CD(4)(+) CD(25)(+)
      Treg cells, which could function in a highly regulatory capacity to suppress Th1
      response.

PMID- 16624085
TI  - [The relationship between metabolic control and the plasma total homocysteine in
      type 2 diabetes treated with insulin].
AB  - OBJECTIVE: To study the relationship between metabolic control and the plasma
      total homocysteine (tHcy) in type 2 diabetes treated with insulin. METHODS: A
      total of 68 patients with type 2 diabetes were recruited. At baseline and the end
      of 3 month therapy, fasting blood samples were collected for measuring fasting
      blood glucose (FBG), HbA1c, tHcy and other routine biochemical testing and
      postprandial blood was collected to measure postprandial blood glucose (PBG).
      RESULTS: FBG, PBG and HbA1c decreased significantly (P < 0.01) after 3 month
      intensive insulin therapy. tHcy also decreased, but the decrease did not reach
      statistic significance (P > 0.05). 7.0% of HbA1c was selected as the cut point
      judging the level of metabolic control. The HbA1c level was less than 7.0% in 31
      (45.6%) patients after insulin treatment alone. In these patients, FBG, PBG and
      HbA1c significantly decreased, when compared with those of pre-treatment. The
      plasma tHcy decreased significantly as well. CONCLUSIONS: After insulin
      treatment, the plasma tHcy decreases when the metabolic control is improved
      significantly.

PMID- 16624086
TI  - [Tumor necrosis factor alpha-induced expression and activity of alveolar
      macrophages matrix metalloproteinase-9 in chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To explore the expression and activity of matrix metalloproteinase-9
      (MMP-9) from alveolar macrophages (AMs) induced by tumor necrosis factor-alpha
      (TNFalpha) in patients with chronic obstructive pulmonary disease (COPD), and
      therefore to study the possible mechanisms. METHODS: AMs were collected from
      bronchoalveolar lavage fluid from patients with COPD, and then were stimulated
      for 24 h with TNFalpha at concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10
      ng/ml, and 20 ng/ml, respectively. The gene expression level of MMP-9 induced by
      TNFalpha was detected by semi-quantitative RT-PCR, and MMP-9 activity was
      measured by zymography. NF-kappaB activity was detected by electrophoretic
      mobility shift assay. RESULTS: In unstimulated AMs, the densitometry unit rate of
      MMP-9 mRNA to beta-actin mRNA was 0.1826 +/- 0.0084. When AMs were stimulated by
      TNFalpha at concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10 ng/ml, and 20
      ng/ml, the densitometry unit rates of MMP-9 mRNA to beta-actin mRNA were 0.4279
      +/- 0.0204, 0.5431 +/- 0.0058, 0.6185 +/- 0.0208, 0.6859 +/- 0.0080, and 0.7784
      +/- 0.0208, respectively. In unstimulated AMs, the densitometry unit of active
      MMP-9 was 10 227 +/- 738, but when AMs were stimulated by TNFalpha at
      concentrations of 0.1 ng/ml, 1 ng/ml, 5 ng/ml, 10 ng/ml, and 20 ng/ml, the
      densitometry units of active MMP-9 were 40,528 +/- 974, 113,741 +/- 4547, 190,696
      +/- 4032, 309,505 +/- 7639, and 427,305 +/- 9145, respectively. NF-kappaB
      activity was significantly elevated after AMs were stimulated by TNFalpha at the
      concentration of 10 ng/ml (P < 0.05). CONCLUSIONS: The expression and activity of
      MMP-9 can be induced by TNFalpha, and the induction was possibly related with the
      NF-kappaB-mediated signal transduction pathway.

PMID- 16624087
TI  - [The association of von Willebrand factor and von Willebrand factor-cleaving
      protease in systemic lupus erythematosus].
AB  - OBJECTIVE: To evaluate the clinical significance of plasma von Willebrand factor
      (vWF) and von Willebrand factor-cleaving protease (vWF-CP) activity in systemic
      lupus erythematosus (SLE). METHODS: vWF antigen (vWF:Ag) and vWF-CP activity were
      respectively evaluated by using ELISA and residual-collagen binding assay (R-CBA)
      in 30 patients with SLE and 40 normal controls. RESULTS: The level of the vWF:Ag
      in SLE patients (114.6 +/- 16.3)% was significantly higher than that in the
      normal controls (71.3 +/- 49.5)% (P < 0.01), while the level of plasma vWF-CP
      activity in the SLE patients (57.7 +/- 16.3)% was significantly lower than that
      in the controls (86.6 +/- 1.8)% (P < 0.01). The level of vWF-CP activity was
      positively correlated with SLE disease activity index (SLEDAI). The alterations
      of these two indices were remarkable in lupus nephritis (LN) patients in
      comparison with those in non-LN patients. The level of vWF-CP activity in type IV
      LN was lowest among the four types of LN (II, III, IV, V). The level of the
      vWF:Ag in 30 SLE patients was reduced four weeks after therapy, on the other
      hand, the vWF-CP activity was significantly increased in those with SLEDAI below
      9, but unchanged in whose with SLEDAI above 9. CONCLUSIONS: The injury of
      endothelial cells and to production autoantibodies against vWF-CP were the
      factors that resulted in lower vWF-CP activity in SLE patients and this lowered
      activity may influence the progression of SLE.

PMID- 16624088
TI  - [A study of cellular telomerase activity in different stages of multiple myeloma
      cells].
AB  - OBJECTIVE: To evaluate the clinical significance of telomerase in multiple
      myeloma (MM) and explore its relationship with cell cycle. METHODS: Marrow plasma
      cells were collected form 21 patients with newly diagnosed or relapsed MM, 2
      patients with monoclonal gammopathy of undetermined significance (MGUS), 15 MM
      patients in complete remission and 10 donors as control. PC isolation from the
      marrow mononuclear cell fraction was performed using immunomagnetic bead
      selection with CD(138) antibodies. Telomerase activity was detected with TRAP
      (Telomerase repeats amplification protocol)-fluorescence. Cell cycle was assayed
      by flow cytometry. RESULTS: (1) The results showed that the positive rate of
      telomerase in all the newly diagnosed and relapsed patients was 90.5%, which was
      higher than that in the control group (10.0%) and the patients in remission
      (13.3%) (P < 0.01). There was no significant difference between the patients in
      remission and control group (P > 0.05), as well as between newly diagnosed and
      relapsed patients (P > 0.05). (2) The average percentage of S period in the
      telomerase positive patients was (18.78 +/- 8.02)%, while that in the negative
      patients was (5.64 +/- 4.03)%; there was statistics difference between them (P <
      0.05). CONCLUSIONS: (1) Telomerase plays an important role in the development of
      MM, it may be used to evaluate disease progression, therapeutic curative effect
      and prognosis; (2) Telomerase activity is expressed in the proliferation period
      of MM cells. Telomerase activity is correlated with cell cycle.

PMID- 16624109
TI  - [Current views on the reference range of serum thyrotropin].

PMID- 16624110
TI  - [Information on diabetes prevention trials must be translated to community
      practice].

PMID- 16624111
TI  - [Problems encountered in training of junior doctors in internal medicine in
      community hospitals should be better realized].

PMID- 16624113
TI  - [The relationship between serum thyroid autoantibodies, iodine intake,
      development and prognosis of Graves' disease].
AB  - OBJECTIVE: To investigate the relationship of thyroid autoantibodies including
      serum thyroid stimulating antibody (TSAb), thyroid stimulation blocking antibody
      (TSBAb) and iodine intake with the development and prognosis of Graves'
      hyperthyroidism. METHODS: A total of 63 subjects with overt hyperthyroidism were
      screened out from 3 Chinese rural communities with different iodine intakes at
      first survey. Serum TSAb, TSBAb, thyrotropin binding inhibitory immunoglobulin
      (TBII), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb)
      were detected. The patients were followed up 2 years later. TSAb and TSBAb were
      measured with recombinant human thyrotropin receptor (rhTSHR)-Chinese hamster
      ovary cell (rhTSHR-CHO cell) bioassay. RESULTS: At the first survey, the
      prevalences of positive TSAb, TBII and TSBAb were found in 80.9%, 61.7% and 6.4%
      of the patients with Graves' disease respectively. TSAb and/or TBII were positive
      in 91.5% of the patients. The consistent rate of TSAb and TBII was 59.6% in the
      cases. All indexes mentioned above were higher in the patients than in healthy
      controls. Positive correlations were found between TSAb and TBII (r = 0.407),
      TSAb and thyroglobulin (r = 0.301), TSAb and thyroid volume (r = 0.317)
      respectively. The prevalence of positive TSAb (91.7%) in Graves' patients in
      iodine excessive area are significantly higher than those in iodine mildly
      deficient area (66.7%). The positive rates and the titers of TBII, TPOAb and TGAb
      were not different statistically among the patients in the three communities. At
      follow-up, the patients with Graves' hyperthyroidism were classified into
      euthyroid group (G1) and hyperthyroid group (G2) according to their outcomes of
      the disease. The TSAb titers and the thyroid volume in the cases of G1 decreased
      significantly, whereas the patients with highly positive TPOAb titers in the
      first survey and the follow-up were hard to become euthyroid and TSAb may be the
      secondary factor influencing the thyroid as compared with TPOAb. CONCLUSION: TSAb
      is more significant than TBII in diagnosing and predicting the outcomes of
      Graves' hyperthyroidism. The application of both TSAb and TBII could raise the
      positive rates of thyrotrophin receptor antibody tests. TSAb, TPOAb titers and
      thyroid volume were factors influencing the prognosis of Graves' hyperthyroidism.

PMID- 16624114
TI  - [A pilot evaluation of the diagnostic value of body mass index in elderly men
      with metabolic syndrome].
AB  - OBJECTIVE: The aim of the study is to determine the relationship between body
      mass index (BMI) and metabolic syndrome and to investigate the epidemiological
      characteristics of this syndrome in elderly men. METHODS: A survey was conducted
      among 683 elderly men aged 65 years and over. To identify the prevalence of
      metabolic syndrome and epidemiological condition of some metabolic indexes after
      grading with BMI, the working definition of Chinese Diabetes Society was
      accepted. The relationship between BMI and certain diseases was analyzed.
      RESULTS: (1) The prevalence of metabolic syndrome increased concomitantly with
      the increase of BMI, when BMI was beyond 23 kg/m(2). (2) There was positive
      correlation between BMI and the number of the abnormal metabolic indexes (r =
      0.557). (3) There was positive correlation between the increase of BMI and the
      levels of systolic blood pressure (SBP), diastolic blood pressure (DBP) and
      triglyceride level (r = 0.189, 0.198 and 0.201 respectively). There was negative
      correlation between the increase of BMI and the level of high density lipoprotein
      cholesterol (r = -0.157). (4) There was positive correlation between the increase
      of BMI and the levels of SBP (r = 0.140) and DBP (r = 0.202) in non-hypertensive
      population. (5) There was positive correlation between the increase of BMI and
      the levels of fasting blood glucose (r = 0.103) and postprandial blood glucose (r
      = 0.113) in non-diabetic population. (6) There was significant increase of BMI in
      the population with coronary heart disease and impairment of kidney function (P <
      0.05). (7) The prevalence of metabolic syndrome was significantly elevated in the
      population with coronary heart disease, impairment of kidney function and
      cerebrovascular disease (P < 0.05). CONCLUSIONS: When BMI is increased, the
      number of abnormal metabolic indexes is increased and the prevalence of metabolic
      syndrome is elevated as well. In the population with the above mentioned
      diseases, the prevalence of metabolic syndrome is high and the BMI of these
      patients is significantly increased.

PMID- 16624115
TI  - [Skeletal biomechanical properties improvement in ovariectomized osteoporotic
      rats of teriparatide was retarded by alendronate].
AB  - OBJECTIVE: To implore the effects of teriparatide (PTH) and alendronate (Alen) on
      skeletal biomechanical properties of ovariectomized (OVX) osteoporotic rats.
      METHODS: 70 female Wistar rats of 6 months were randomly divided into 7 groups:
      (1) Baseline: sacrificed at baseline; (2) OVXb: sacrificed in 6 weeks after OVX;
      (3) Sham operation; (4) OVXe: sacrificed 14 weeks after OVX; (5) PTH: 40
      microg.kg(-1).d(-1); (6) Alen: 100 microg.kg(-1).d(-1); (7) A + P: PTH 40
      microg.kg(-1).d(-1) and Alen 100 microg.kg(-1).d(-1). In group (5)-(7), different
      medicines were injected 5 times per week from 6th to 14th week after OVX. The
      cancellous biomechanical properties were measured with indentation test and the
      cortical properties were investigated with three-point bending test. RESULTS: (1)
      The can load and can stiff of distal femur of OVXb were significantly lower than
      those of baseline (P < 0.01). It is indicated that osteoporotic rat models with
      impaired bone strength were established. (2) The can load and can stiff of distal
      femur of PTH [(36.3 +/- 9.2) N, (160.7 +/- 48.0) N/mm(2)], Alen [(42.7 +/- 13.0)
      N, (122.9 +/- 35.6) N/mm(2)] and A + P [(44.3 +/- 18.2) N, (105.2 +/- 58.4)
      N/mm(2)] groups were all higher than those of OVXe [(19.5 +/- 8.5) N, (83.2 +/-
      37.7) N/mm(2), P < 0.001 or P < 0.01]. In femoral shaft, maximal load and elastic
      load in PTH, Alen and A + P groups were higher than those of OVXe (P < 0.001, P <
      0.01 or P < 0.05). (3) Can stiff in distal femur was higher in PTH than that in
      Alen and A + P groups (P < 0.05). Elastic load, maximal load and energy
      absorption in femoral shaft were higher in PTH and A + P groups than those in
      Alen group (P < 0.05), and maximal stress was higher in PTH than that in A + P
      and Alen group (P < 0.05). CONCLUSION: PTH and Alen were effective in improving
      the skeletal mechanical properties of OVX rats, but improvement in Alen and A + P
      was not so good as that in PTH group. It is indicated that anabolic effects of
      PTH was retarded by Alen's significant inhibition of bone turnover, therefore,
      PTH and Alen should not be utilized simultaneously.

PMID- 16624116
TI  - [A clinical analysis of 32 cases of POEMS syndrome].
AB  - OBJECTIVE: To compare the clinical features of POEMS (polyneuropathy,
      organomegaly, endocrinopathy, M protein and skin changes) syndrome patients from
      Peking Union Medical College Hospital (PUMCH) with those of patients in previous
      reports. METHODS: Thirty-two patients with POEMS syndrome were identified in
      PUMCH over the last two decades. The clinical features of these patients were
      compared with those in other large series from Japan, China, and the United
      States. RESULTS: The average age at presentation was 45.8 years; 22 were men. All
      32 patients had polyneuropathy and decreased knee-jerk reflex. Organomegaly was
      present in 31 patients. Nine patients underwent lymph node biopsy and 5 of them
      were proven to have Castleman's disease. Twenty-six patients had at least one
      endocrine abnormality at time of presentation, not including more commonly
      prevalent diseases like diabetes mellitus or hypothyroidism. Seventy-two percent
      (18/25) of the patients had a detectable monoclonal protein with serum
      immunofixation, but only 16.7% (4/24) had positive results with serum protein
      electrophoresis. Skin changes were documented in 30 patients. In comparison with
      other series, we found a higher prevalence of organomegaly and papilloedema. The
      rates of M protein level, however, were similar. CONCLUSIONS: Most features of
      our series are similar to those from previous foreign series. The prevalence of M
      protein in our study was similar to that in previous foreign series, but was not
      as low as reported in previous Chinese studies. Immunofixation and
      immunohistochemical staining of bone marrow biopsies are probably more sensitive
      in detecting M protein as compared with serum protein electrophoresis.

PMID- 16624117
TI  - [The application of adenosine stress myocardial perfusion tomographic imaging in
      detecting coronary artery disease].
AB  - OBJECTIVE: To analyze the sensitivity and specificity of adenosine stress
      myocardial perfusion tomographic imaging for the diagnosis of coronary artery
      disease (CAD). METHODS: Adenosine was infused intravenously at a rate of 140
      microg.kg(-1).min(-1) for 6 minutes. 3 minutes after adenosine infusion, 925 MBq
      of (99m)Tc-MIBI were injected intravenously. SPECT myocardial imaging acquisition
      was obtained 1.5 hours after adenosine infusion. If the result was abnormal, rest
      myocardial perfusion imaging would be performed next day. Coronary angiography
      was performed in all patients within one week of myocardial imaging. RESULTS:
      Total 79 cases [(62 +/- 10) years old, 35 men, 44 women] were included in this
      study. In the 50 cases of CAD patients confirmed by coronary angiography, 44
      patients have positive adenosine (99m)Tc-MIBI myocardial perfusion SPECT.
      Nineteen out of 29 cases without CAD have negative adenosine myocardial perfusion
      tomographic imaging. The sensitivity and specificity of adenosine myocardial
      perfusion tomographic imaging for the diagnosis of CAD were 88.0% and 65.5%. The
      sensitivity of adenosine myocardial perfusion tomographic imaging for diagnosing
      coronary stenosis in left anterior descending, left circumflex and right coronary
      artery are 32/40, 21/27 and 31/32. There was no severe adverse side effect during
      adenosine stress test. CONCLUSION: Adenosine stress myocardial perfusion
      tomographic imaging is an useful non-interventional method for detecting coronary
      artery disease.

PMID- 16624118
TI  - [The application of transcranial Doppler in the evaluation of brain function in
      deeply comatose patients].
AB  - OBJECTIVE: To study the cerebral blood flow changes in irreversible comatose
      patients and investigate the correlation between the results of transcranial
      Doppler (TCD) and clinical evaluation of brain function. METHODS: TCD studies
      were performed in 92 patients who were excluded from the possibility of
      reversible coma and all of them had Glasgow Coma Scale of 3. Their brain stem
      reflections all disappeared. Detection of the blood flow in bilateral middle
      cerebral arteries was carried out through temporal window in all the patients and
      in 42 of the 92 cases the blood flow of the basilar artery was detected through
      occipital or peri-occipital window. Bilateral middle cerebral artery were taken
      as the main arteries for evaluation. The positive standard is the appearance of
      one of the following characteristic blood flow, i.e. brief systolic forward flow
      or systolic spikes and diastolic reverse flow, brief systolic forward flow or
      systolic spikes and no diastolic flow and no detectable flow signals. The
      examination was repeated after 12 h. RESULTS: 68 cases were positive in the
      initial examination (73.9%) and 74 cases were positive after 12 h (80.4%).
      CONCLUSION: TCD can be an effective and objective index in the evaluation of
      irreversible termination of brain function.

PMID- 16624119
TI  - [Cerebral ischemia manifested as recurrent loss of consciousness].
AB  - OBJECTIVE: To demonstrate the clinical characteristics of cerebral ischemia that
      mainly manifested as recurrent loss of consciousness and to explore the
      pathogenesis of these incidents. METHODS: Twelve patients who had cerebral
      ischemia that manifested mainly as recurrent loss of consciousness were
      retrospectively studied. Their risk factors, clinical characteristics, cranial
      MRIs, angiograms and perfusion images were recorded in detail. The patients were
      followed up for at least 90 days. RESULTS: Every patient had at least one risk
      factor for cerebrovascular disease. The clinical manifestations in most of the
      patients are syncope-like incidents, but the duration was longer, lasting for
      minutes to hours, but mostly less than 24 hours. These patients could be sorted
      into three types according to the angiographic data: type A severe stenosis in
      anterior circulation (mostly on both sides); type B severe stenosis in posterior
      circulation; and type C multiple severe stenosis (in both anterior and posterior
      circulation). Cerebral blood flow was severely reduced in the stenotic arteries
      as shown by angiogram. The perfusion studies in type A patients also showed
      diffuse hypoperfusion of cerebrum. In one case, the patient lost his
      consciousness when the Angioguard (a protective guidewire) passed through the
      stenosis, and he regained consciousness when the stent was fully-opened in a few
      minutes. All the 12 patients received medical therapy. Four patients who were
      ineffective with medical treatment along received stent angioplasty and there was
      no incident during the follow-up. Six of the remaining eight patients with
      medical treatment alone had ischemic strokes within 90 days, including two with
      disabling strokes. CONCLUSIONS: Recurrent loss of consciousness is a rare
      manifestation of large cerebral artery stenosis. The probable mechanism may be
      diffuse hypoperfusion in cerebrum or brainstem. These patients are in high risk
      of stroke. Interventional therapy to revascularize the cerebral circulation may
      be a rational treatment.

PMID- 16624120
TI  - [A short-term efficacy and safety study of infliximab in active ankylosing
      spondylitis].
AB  - OBJECTIVE: To evaluate the efficacy and safety profile of a loading regimen of
      the anti-TNFalpha antibody infliximab in ankylosing spondylitis (AS). METHODS:
      This was an open-labeled trial. Subjects eligible for this study were adults with
      a diagnosis of definite AS. Active disease was a Bath AS disease activity index
      (BASDAI) > or = 4 and spinal pain VAS > or = 4. Concurrent stable treatment with
      nonsteroidal anti-inflammatory drugs was permitted during the study. Subjects
      were not permitted to be on methotrexate, systemic corticosteroids, cytotoxic
      drugs or disease-modifying anti-rheumatic drugs for various time periods before
      screening. Infliximab 5 mg/kg was infused at weeks 0, 2, 6. All patients were
      followed up to 10 weeks. The primary endpoint was proportion of ASAS 20
      responders at week 10. The secondary endpoints were the proportion of subjects
      achieving an ASAS partial remission, the change from baseline in bath AS
      functional index and in the physical component summary score of the short form-36
      in health survey questionnaire at week 10. Other secondary endpoints, related to
      reducing signs and symptoms of AS and improving range of motion and physical
      function, were evaluated. RESULTS: 63 patients (79% males, 90% HLA-B(27)(+),
      median age 32 yr, median disease duration 10 yr) completed the treatment. The
      proportion of ASAS 20 responders at 2, 6, 10 week was 75%, 84%, 84% respectively.
      The proportion of ASAS partial remission patients at 2, 6, 10 week was 10%, 21%,
      30% respectively. Results for other secondary efficacy endpoints showed that
      infliximab could provide substantial benefits to patients with AS by reducing
      clinical signs and symptoms and improving range of motion, physical function, and
      quality of life. Sixty-five percent of subjects reported treatment-related
      adverse events. The most frequently occurred were upper respiratory tract
      infection and skin and appendages. Secondary was elevation of liver enzymes. Most
      treatment-related adverse events were mild to moderate in severity. Two patients
      had serious dermatitis and one stopped treatment owing to an infusion reaction.
      Short-term follow up indicated that effect of Remicade lasted for about 2 to 8
      months without any new side effect. CONCLUSION: A loading regimen of infliximab
      demonstrated consistent evidence of efficacy and was well tolerated in the
      treatment of active AS.

PMID- 16624121
TI  - [The clinical and pathological characteristics of histiocytic necrotizing
      lymphadenitis: analysis of 52 cases].
AB  - OBJECTIVE: To study the clinical manifestation and pathological features of
      histiocytic necrotizing lymphadenitis (Kikuchi's disease, KD). METHODS: 52
      patients with KD were collected to analyze the clinical manifestation,
      pathological features of biopsy lymph nodes, diagnosis and treatment. RESULTS: 41
      cases (79%) were female of the 52 patients. The main clinical features included
      persistent fever (100%), single (23%)/multi (77%)-lymphadenopathy (always in
      cervical region), pleomorphism erythra (35%), neutropenia (76%), elevated
      erythrocyte sedimentation rate (100%), insensitivity to antibiotics (100%) and
      sensitivity to small dosage glucocorticoid (81%). 26 cases (50%) had elevated
      aspartate aminotransferase and/or alanine aminotransferase, but only 7 cases
      (13%) had upper respiratory tract symptom like influenza. Pathological features
      included distinctive necrosis, loss of lymph node structure, infiltration with
      histiocytes and lymphocytes, absence of neutrophils. Immunohistochemical
      stainings showed CD(68) positive for histiocytes and CD(3), CD(45) RO positive
      for T lymphocytes. CONCLUSION: Diagnosis of KD relies on the pathological
      examination and immunohistochemical staining.

PMID- 16624123
TI  - [The outcomes of the thirty patients with refractory leukemia treated with
      related HLA haploidentical stem cells transplantation].
AB  - OBJECTIVE: To assess the outcomes of the therapy for patients with refractory
      leukemia with HLA haploidentical stem cells transplantation. METHODS: To analyze
      the outcomes of 30 patients with refractory leukemia who underwent HLA
      haploidentical peripheral blood stem cells transplantation from August 1998 to
      August 2004. RESULTS: Thirty refractory leukemia patients including 13 cases of
      acute non-lymphocytic leukemia, 10 cases of acute lymphocytic leukemia (ALL), 6
      cases of chronic myeloid leukemia and 1 case of phase IV non-Hodgkin's lymphoma
      underwent HLA haploidentical peripheral blood stem cells transplantation. The
      median age was 25 years old (3-52 years old). Twelve patients received stem cells
      from parent donors, four from daughter or son donors and the remaining from
      sibling donors. Three HLA loci mismatched in twelve cases, two HLA loci
      mismatched in thirteen cases and one HLA locus mismatched in five cases. The
      conditioning regime consisted of fludara (25 mg/m(2) x 5 d), busulfan (4 mg/kg x
      4 d) and cyclophosphamide (60 mg/kg x 2 d). Rabbit anti-human lymphocyte globulin
      (5 mg/kg x 5 d) was added in some patients in the conditioning regime. A mean of
      5.0 (2.9-8.0) x 10(8)/kg mononucleated cells was grafted. The number of mean
      CD(34)(+) cells was 5.5 (3.0-6.5) x 10(6)/kg. Twenty-seven patients were
      successfully grafted, one failed to graft, one died from severe fungal infection
      at day 2 and one died from severe veno-occlusive disease at day 28. The mean time
      of white cell count more than 1.0 x 10(9)/L was 14 (11-18) days and platelet
      count more than 20 x 10(9)/L was 15 (11-18) days. ALL the 27 successfully grafted
      patients got complete remission. Severe acute graft versus host disease occurred
      in six patients and four of them died. Seven patients suffered from chronic graft
      versus host disease. Seven patients relapsed and died. The median relapse time
      was 10 (3-24) months. Fourteen patients are still surviving, and ten have disease
      free survival. CONCLUSION: It is concluded from our observation that HLA
      haploidentical peripheral blood stem cells transplantation may be an effective
      therapy for refractory and relapse leukemia. Some patients with refractory and
      relapse leukemia treated with HLA haploidentical stem cells transplantation may
      have disease free survival. Graft versus leukemia effect may be strong in
      patients receiving HLA haploidentical blood stem cells transplantation and
      leukemia will probably be relapsed when the patient without complete remission
      was treated with this therapy.

PMID- 16624125
TI  - [The expression of capillary hypoxia-induced factor-alpha and pulmonary artery
      remodeling in chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To observe the expression of hypoxia-inducible factor-alpha (HIF
      1alpha, HIF-2alpha, HIF-3alpha) and pulmonary vascular remodeling in pulmonary
      arteries of patients with chronic obstructive pulmonary disease (COPD). METHODS:
      Pulmonary specimens were obtained from patients undergoing lobectomy for lung
      cancer, of whom 12 had concurrent COPD and 10 without COPD. Pulmonary vascular
      remodeling was observed with optical microscope, and HIF-alpha mRNA and protein
      were detected by in situ hybridization and immunohistochemistry respectively.
      RESULTS: Vascular remodeling parameters (WT%, WA%) of COPD patients [(24 +/- 3)%,
      (48 +/- 6)%, respectively] were statistically different from those of the control
      subjects [(15 +/- 2)%, (39 +/- 4)%, respectively]. Relative quantification of
      mRNA and protein levels (absorbance, A) showed that HIF-1alpha in COPD group
      (0.172 +/- 0.011, 0.089 +/- 0.013, respectively) were statistically higher than
      those of the control subjects (0.103 +/- 0.010, 0.042 +/- 0.010, P < 0.01).
      Furthermore, they correlated positively with the parameters for vascular
      remodeling. The mRNA and protein levels of HIF-2alpha in COPD group (0.038 +/-
      0.010, 0.077 +/- 0.010, respectively) were significantly lower than those of the
      control subjects (0.133 +/- 0.017, 0.169 +/- 0.010, respectively, P < 0.01), and
      correlated negatively with the parameters for vascular remodeling. Regarding HIF
      3alpha, only the mRNA level in COPD group (0.077 +/- 0.010) was statistically
      lower than that of the control subjects (0.088 +/- 0.010) (P < 0.05), and no
      correlation with vascular remodeling parameters was observed. CONCLUSIONS:
      Pulmonary vascular remodeling in COPD patients was accompanied by the
      differential expression of HIF-alpha gene, which may be involved in the process
      of hypoxic pulmonary vascular remodeling in COPD.

PMID- 16624124
TI  - [A study on the expression of myeloid cell leukemia 1 proteins and survivin and
      their relation with B cell apoptosis in non-Hodgkin's lymphoma].
AB  - OBJECTIVE: To explore the expression of myeloid cell leukemia 1 (MCL-1) proteins
      and survivin and its correlation with cell apoptosis as well as with the
      development and progression of B cell non-Hodgkin's lymphoma (B-NHL). METHODS:
      TdT-mediated dUTP nick end labeling and immunohistochemistry were used to study
      cell apoptosis and expression of MCL-1 proteins and survivin proteins in 43
      patients with B-NHL and 10 with reactive hyperplasia (RH) lymphoid tissue.
      RESULTS: The positive rate of MCL-1 proteins and survivin proteins was 58.1%
      (25/43) and 69.8% (30/43) respectively. The expression of MCL-1 proteins was not
      detected in RH lymphoid tissue, but that of survivin was detected in 10.0%
      (1/10). The expression of MCL-1 proteins in aggressive B-NHL was higher than that
      in indolent B-NHL (70.0 % vs 30.8 %, P < 0.05). The expression of survivin in
      aggressive B-NHL was also higher than that in indolent B-NHL (80.0% vs 46.2%, P <
      0.05). Apoptotic index (AI) was not correlated positively with the expression of
      MCL-1, but correlated positively with the expression of survivin (r = 0.429, P <
      0.01). MCL-1 and survivin were correlated positively in B-NHL (r = 0.598, P <
      0.001). CONCLUSIONS: MCL-1 proteins as family member of BCL-2 have no influence
      on apoptosis but survivin may participate in the regulation mechanism of B-NHL
      apoptosis. It is indicated that the two proteins with a close relationship may
      take part in the development and progression of B-NHL.

PMID- 16624140
TI  - [Sleep breathing disorders: a view of conceptions and syndrome definition].

PMID- 16624142
TI  - [Consensus and practice of empirical therapy and target therapy for antimicrobial
      agents].

PMID- 16624144
TI  - [Gastroesophageal reflux disease: questions and challenges].

PMID- 16624145
TI  - [Relationship between obstructive sleep apnea/hypopnea syndrome and insulin
      resistance].
AB  - OBJECTIVE: To investigate whether obstructive sleep apnea/hypopnea syndrome
      (OSAHS) is independently associated with insulin resistance (IR). METHODS: We
      recruited 60 male obese patients with OSAHS [OSAHS group, age (42.3 +/- 2.6)
      years, body mass index (BMI) (28.3 +/- 2.1) kg/m2, waist/hip ratio (WHR) 0.95 +/-
      0.05], 60 male weight-matched obese patients without OSAHS [OB group, age (41.5
      +/- 3.1) years, BMI (27.7 +/- 1.5) kg/m2, WHR 0.94 +/- 0.04] and 60 male normal
      weight subjects [NW group, age (41.8 +/- 2.4) years, BMI (22.6 +/- 1.9) kg/m2,
      WHR 0.86 +/- 0.05]. The subjects underwent polysomnography and OSAHS was defined
      as an apnea-hypopnea index (AHI) > or = 5. The systolic blood pressure and
      diastolic blood pressure were measured. IR was evaluated by fasting serum true
      insulin (TI) level and IR index based on the homeostasis model assessment method
      (HOMA-IR). In the OSAHS group, multiple linear regression was used with either TI
      or HOMA-IR as the dependent variable, and the corresponding set of independent
      variables included age, BMI, WHR, AHI and minimum oxygen saturation (MSpO2).
      RESULTS: After adjustment for age, BMI, and WHR, the OSAHS group was more insulin
      resistant, as indicated by the higher levels of TI and HOMA-IR. Multiple linear
      regression showed that the central obesity parameter (WHR) was the major
      determinant of IR of the OSAHS group, while sleep-disordered breathing parameters
      (AHI and MSpO2) were also independent determinants of IR of the group (TI: AHI P
      = 0.017, TI: MSpO2 P = 0.005; HOMA-IR: AHI P = 0.008, HOMA-IR: MSpO2 P = 0.003).
      CONCLUSION: OSAHS may be independently associated with IR.

PMID- 16624147
TI  - [The effect of nasal continuous positive airway pressure on endothelial function
      in obstructive sleep apnea-hypopnea syndrome with coronary heart disease].
AB  - OBJECTIVE: To study the association between the indices of endothelial function
      in obstruction sleep apnea-hypopnea syndrome (OSAHS) and coronary heart disease
      (CHD) and the effect of nasal continuous positive airway pressure (nCPAP) on the
      combination of OSAHS and CHD. METHODS: A total of 80 subjects were prospectively
      recruited into four groups including control, OSAHS, CHD, OSAHS with CHD groups,
      with 20 subjects each. The indices of sleep apnea, serum nitric oxide (NO), and
      plasma endothelial-1 (ET-1) were measured. The changes of concentration of ET-1
      and NO were compared before and after nCPAP therapy. The associations between ET
      1 and NO and MSpO2, CT90 were analyzed. RESULTS: (1) Multi-variable logistic
      analysis showed that OSAHS was one of the risk factors for CHD (OR = 0.511). (2)
      Compared with the control subjects and CHD group, there were significantly higher
      values of CT90, concentrations of ET-1 and lower values of MSpO2, concentrations
      of NO in both OSAHS and OSAHS with CHD groups (P < 0.01). There were no
      significant difference in sleep apnea indices between OSAHS and OSAHS with CHD
      groups (P > 0.05). However, in the group of OSAHS with CHD, the plasma ET-1 was
      significantly higher, whereas the serum NO was significantly lower than that in
      the group of OSAHS alone (P < 0.01). (3) The concentration of serum NO in the
      group of OSAHS was positively correlated with MSpO2 (r = 0.519, P < 0.05) and
      inversely correlated with CT90 (r = -0.529, P < 0.05). In addition, the
      concentration of plasma ET-1 was inversely correlated with MSpO2 (r = -0.457, P <
      0.05) and positively correlated with CT90 (r = 0.476, P < 0.05). (4) In the
      groups of OSAHS and OSAHS with CHD, MSpO2, NO and NO/ET-1 after nCPAP therapy
      were higher than those before therapy, while CT90 and ET-1 were lower than those
      before therapy (P < 0.01). CONCLUSIONS: OSAHS is one of the risk factors for CHD.
      Endothelial function was significantly impaired in OSAHS patients, and more
      severe in patients with OSAHS with CHD. The impairment of endothelial function
      may be one of the main mechanisms for the development or deterioration of CHD in
      OSAHS patients. The vascular endothelial dysfunction can be ameliorated by nCPAP
      treatment, which is correlated with improvement of nocturnal hypoxemia.

PMID- 16624148
TI  - [The prognostic value of extravascular lung water index in critically ill septic
      shock patients].
AB  - OBJECTIVE: To investigate the prognostic value of extravascular lung water index
      (EVLWI) in critically ill patients with septic shock in intensive care unit
      (ICU). METHODS: EVLWI was determined by using a PiCCO Monitor, and the daily
      fluid balance was recorded. RESULTS: Fifty patients with septic shock were
      admitted and twenty-six patients survived. The average EVLWI at baseline was 11.7
      ml/kg, and the difference was not different between survivors and nonsurvivors, P
      = 0.551. The EVLWI of day 3 (EVLWI(d3)) in nonsurvivors was significantly higher
      than the survivors [(14.3 +/- 8.8) ml/kg vs (8.1 +/- 2.7) ml/kg, P = 0.001]. If
      the patients were divided into three groups by the EVLWI(d3), group one 0-7 ml/kg
      (4/16), group two 8-14 ml/kg (10/24), and group three > 14 ml/kg (10/10), the
      hospital mortality of the third group was significantly higher than the other two
      groups (P = 0.000, 0.002). There was a significant difference between the
      survivors and the nonsurvivors in the fluid balance at the first day and the
      following three days (P = 0.000, 0.000). Negative fluid balance was associated
      with a lower mortality. By using receiver operating characteristic analysis, the
      area under the curve was 0.740 +/- 0.072 to EVLWI(d3). If EVLWI > 7.5 ml/kg, the
      sensitivity and the specificity of accurate judgment were 83.3% and 53.8%.
      CONCLUSION: Dynamic observation of EVLWI can be one of the factors for predicting
      the prognosis of patients with septic shock. A reduction of EVLWI at early
      treatment and a negative fluid balance were associated with a better prognosis.

PMID- 16624149
TI  - [Expression and significance of severe acute respiratory syndrome associated
      coronavirus (SARS-CoV)-X4 protein in lungs of SARS patients].
AB  - OBJECTIVE: To investigate the significance of severe acute respiratory syndrome
      associated coronavirus (SARS-CoV)-X4 protein expression in lungs of patients with
      SARS. METHODS: Pathological features of the lungs from 4 SARS patients were
      examined and the expression of SARS-CoV-X4 protein in the lungs was evaluated
      with immunohistochemical staining using specific antibodies against protein X4.
      RESULTS: Microscopically, all lungs from 4 cases showed edema, erythrocyte and
      fibrin exudates in the alveoli, hyperplasia of alveolar epithelium, necrosis,
      hyaline membrane formation and fibroblast foci. Immunohistochemical stains showed
      a strong positivity of X4 protein in denudation cells, vascular endothelial cells
      and also erythrocytes and neutrophils in the alveoli of the lung tissues from the
      4 cases. CONCLUSIONS: Expression of SARS-CoV-X4 protein in the lungs may be
      involved in the pathogenesis and progression of SARS.

PMID- 16624150
TI  - [Determination and significance of interleukin-16 in tuberculous and malignant
      pleural effusion].
AB  - OBJECTIVE: Interleukin-16 (IL-16) is a chemoattractant of CD4+ lymphocytes, and
      it has been implicated in the pathogenesis of various inflammatory diseases. The
      aim of the present study was to measure IL-16 in pleural effusions caused by
      tuberculosis and malignancy and its relationship with cell and differential
      counts as well as lymphocyte subsets. METHODS: Pleural effusion and venous blood
      samples were collected from 32 patients with tuberculous pleuritis and 30 lung
      cancer patients with malignant effusion. Analysis of pleural effusion for total
      leukocytes and cell differentials of leukocytes was performed. Three-color flow
      cytometry was performed to determine T lymphocyte subsets in cell pellets of
      pleural effusion. The concentration of IL-16 in cell-free supernatants of pleural
      effusion and sera was measured by a sandwich enzyme-linked immunosorbent assay.
      RESULTS: In all the studied patients, the level of IL-16 was significantly higher
      in pleural effusion than in serum. The levels of IL-16 were significantly higher
      in tuberculous than in malignant effusions. In pleural effusion, positive
      correlations were found between the IL-16 levels and total cell counts,
      lymphocytes, CD3+ T cells, as well as CD4+ T cells. CONCLUSIONS: Compared to
      malignant pleural effusion, IL-16 appeared to be increased in tuberculous pleural
      effusion. The pleural effusion IL-16 levels were positively related to the
      numbers of CD4+ T cells, suggesting that IL-16 might be capable of inducing CD4+
      T cell infiltration into pleural space.

PMID- 16624153
TI  - [The association of cardiovascular risk factors and prevalence of carotid
      atherosclerosis at 10 years].
AB  - OBJECTIVE: To explore the association of cardiovascular disease (CVD) risk
      factors and its impact on the 10-year prevalence of carotid atherosclerosis.
      METHODS: Two surveys for CVD risk factors were carried out in a population
      consisting of 1323 subjects in Beijing in both 1992 and 2002 and a direct
      measurement of carotid arteries with B-mode ultrasound imaging were performed in
      2002. Intima-media thickness (IMT) and plaque of carotid arteries were regarded
      as the indicators of carotid atherosclerosis and main CVD risk factors were
      treated as the impact factors. RESULTS: (1) 10-year prevalence of carotid
      atherosclerosis continually increased with elevated baseline risk factors levels.
      Age, smoking, hypertension and hypercholesterolemia were found to be
      independently associated with carotid atherosclerosis. (2) 10-year prevalence of
      carotid atherosclerosis increased with the elevated number of risk factors
      clustering in individuals. (3) The prevalence of IMT and plaque were 67.1% and
      42.6% in subjects with CVD risk factors in both 1992 and 2002 surveys with Odds
      Ratios being 1.7 and 3.1 times as those without risk factors. CONCLUSION:
      Traditional CVD risk factors exert impact on CVD and carotid atherosclerosis with
      different degrees and carotid atherosclerosis can be regarded as an early
      evaluation indicator for risk of atherosclerotic diseases.

PMID- 16624151
TI  - [The risk factors and impact of gastroesophageal reflux disease on quality of
      life in general population].
AB  - OBJECTIVES: To assess the risk factors of gastroesophageal reflux disease (GERD)
      in the general population and its impact on health-related quality of life
      (HRQOL). METHODS: A face-to-face interview was carried out in Guangdong Province
      using a validated Chinese version Reflux Disease Questionnaire (RDQ) to assess
      the prevalence of GERD. Random clustered sampling of permanent inhabitants aged
      18 to 90 years was carried out under stratification of urban and suburban areas.
      The impact of GERD on HRQOL was evaluated using the Chinese version of SF-36. The
      statistical analysis was performed with SPSS 10.0 programs. RESULTS: A total of
      83 GERD patients were collected and 166 healthy subjects were selected as
      control. There was no difference in prevalence between male (2.6%) and female
      (2.4%). There was no significant association between age and prevalence of GERD
      symptoms. Divorced/widowed/separated subjects (OR 4.61) and subjects with severe
      working burden (OR 3.43) were significantly more likely to report GERD symptoms.
      As compared with the general population, subjects with GERD symptoms experienced
      considerable impairment in quality of life. CONCLUSIONS: Psychosocial factors may
      play important roles in the production of GERD symptoms. GERD has a negative
      impact on HRQOL.

PMID- 16624154
TI  - [Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive
      cardiomyopathy].
AB  - OBJECTIVE: Gauging the acute effect of Percutaneous transluminal septal
      myocardial ablation (PTSMA) as a treatment for hypertrophic obstructive
      cardiomyopathy (HOCM). METHODS: PTSMA was performed in 52 patients with
      symptomatic HOCM [mean age (44.7 +/- 11.9), male 38, female 14]. All patients had
      echocardiography performed prior to the procedure, 3-7 days post-PTSMA. RESULTS:
      Procedure success was achieved in 41 patients, success rate was 78.8%. The
      average left ventricular outflow tract (LVOT) gradient was (92.64 +/- 38.69) mm
      Hg before the procedure, and (51.79 +/- 38.99) mm Hg after the procedure (P <
      0.001). The thickness of interventricular septum (IVS) was (22.96 +/- 5.15) mm
      before the procedure and became (21.27 +/- 4.64) mm 3-7 days post-PTSMA (P <
      0.05). The incidence of right bundle branch block development post-PTSMA was
      15.38% (> 48 h), and one patient (1.92%) had complete heart block. Two patients
      died. CONCLUSION: PTSMA is an effective non-surgical procedure for symptomatic
      patients with HOCM because of its low risk and its significant hemodynamic and
      echocardiographic improvement.

PMID- 16624155
TI  - [The effects of glutathione S-transferase (GSTT1 and GSTM1) genes polymorphisms
      on treatment efficacy and prognosis of acute myeloid leukemia].
AB  - OBJECTIVE: To investigate the impact of GSTT1 and GSTM1 genotypes on response,
      drug side effects and prognosis of acute myeloid leukemia (AML). METHODS: GSTT1
      and GSTM1 genotypes were analysed in 180 AML patients with PCR. Complete
      remission (CR) rate, drug side-effects, overall survival, relapse-free survival
      and relapse rate were compared in groups with or without GSTT1 and GSTM1 genes.
      RESULTS: (1) The CR rate (96.9%) in GSTT1 and GSTM1 genes double-present patients
      was significantly higher than that in patients of GSTT1 null or GSTM1 null (CR
      rate 78.0%) (P = 0.013). The risk of failure to achieve CR in patients with GSTT1
      null/GSTM1 null is 8.736 times higher than that in patients with GSTT1 and GSTM1
      genes double-present (odds ratio OR was 8.736, 95% CI was 1.146 - 66.574). The CR
      rate (88.4%) in GSTT1 present patients was also significantly higher than that in
      patients of GSTT1 null (CR rate 74.7%) (P = 0.021, OR = 2.572, 95% CI 1.136 -
      5.826). (2) There was no significant relationship between GSTT1/GSTM1 genotypes
      and the lasting time of neutrophilic granulocyte (ANC) < 0.5 x 10(9)/L and PLT <
      20 x 10(9)/L. The risk of ALT abnormality in patients with GSTM1 null is 2.593
      times higher than that in patients with GSTM1 present (P = 0.016, 95% CI 1.176 -
      5.717). (3) Overall survival and relapse-free survival of GSTT1 and GSTM1 double
      present patients were significantly better than those in patients of GSTT1
      null/GSTM1 null (mean overall survival was 68.4 months vs 38.5 months, P = 0.028,
      and mean relapse-free survival was 73.5 months vs 34.9 months, P = 0.014,
      respectively). Relapse-free survival in GSTT1 null patients was significantly
      shorter than that in patients with GSTT1 present (26.7 months vs 64.3 months, P =
      0.038), but there was no significant difference of overall survival between the
      two groups. The relapse rate of double-present patients was significantly lower
      than that of GSTT1 null/GSTM1 null patients (13.3% vs 35.6%, P = 0.019).
      CONCLUSION: GSTT1 and GSTM1 genotypes were apparently related with response, drug
      side effects and prognosis of patients with AML. GSTT1 and GSTM1 genotype might
      be useful in selecting appropriate chemotherapy regimens for patients with AML.

PMID- 16624156
TI  - [Partial deletion of chromosome 13 long arm in multiple myeloma and its clinical
      significance].
AB  - OBJECTIVE: To explore the specific locus deletion of the long arm of chromosome
      13 and its relationship with the clinical behavior and prognosis of multiple
      myeloma (MM). METHODS: FISH analysis was performed on bone marrow smears from 68
      patients with MM to study the deletion of Rb-1 gene and locus 13q14.3 on
      chromosome 13. The statistic value of its effect on clinical features were
      determined. RESULTS: 35 out of the 68 (51%) cases were found with deletion of
      chromosome 13; deletion of Rb-1 gene were found in 29 (43%) cases; deletion of
      locus 13q14.3 were found in 23 out of 44 (52%) cases; the analysis results were
      same in 66% of the cases (29/44) with the above two probes. Chi-square test
      showed that partial deletion of chromosome 13 was associated with clinical
      behavior, early chemotherapy response and 1 year survival. CONCLUSION: Deletion
      of Rb-1 gene and locus 13q14.3 were both common cytogenetic changes in MM
      patients with effect on the biological behavior of the disease.

PMID- 16624158
TI  - [The effect of cyclophosphamide, thalidomide and dexamethasone combination
      therapy in relapsed/refractory multiple myeloma].
AB  - OBJECTIVE: To investigate the effect of the combination of thalidomide,
      cyclophosphamide and dexamethasone for the treatment of relapsed/refractory
      multiple myeloma. METHODS: 20 relapsed/refractory multiple myeloma patients
      received thalidomide (200 mg/d), cyclophosphamide (300 mg.m(-2).d(-1), d1-4,
      every 4 weeks) and pulsed dexamethasone (20-40 mg/d, d1-4, every 4 weeks).
      RESULTS: After 3 cycles of therapy, 9 cases obtained partial remission (PR), 4
      had minimal responses (MR), 5 were of no change and 2 had progressive disease.
      After 6 cycles of therapy, 13 patients achieved PR and 5 had MR. CONCLUSION: The
      combination of thalidomide, cyclophosphamide and dexamethasone is a promising
      treatment regime for relapsed/refractory multiple myeloma.

PMID- 16624183
TI  - Subfertility treatment in developing countries: attending to what women want.

PMID- 16624184
TI  - Health care utilization for diarrhea and fever in 4 urban slums in Karachi.
AB  - OBJECTIVE: To estimate the fraction of fever and diarrhea patients making use of
      private practitioners, self-treatment, hospital care, drug vendors, community
      health centers and traditional healers. DESIGN: A cross-sectional survey. PLACE
      AND DURATION OF STUDY: Four slums in and around Karachi during October and
      November, 2001. PATIENTS AND METHODS: A sample of 1842 households was selected
      with probability proportional to size of the slum. The household head or a
      representative was asked regarding the treatment providers for diarrhea and cases
      of fever persistent for 3 days or more. Only households with an actual case of
      fever and/or diarrhea were included in the analysis. RESULTS: The study found
      that more than half of diarrhea and fever cases are seen by private
      practitioners. Self medication with medicines available in the home or
      specifically purchased for the disease episode from a drug vendor combined
      provides 13% to 18% of health care. Only between 11% and 13% of patients are seen
      by the public sector, hospitals and community health centers. There was no
      significant difference between the choice of health care provider for diarrhea
      and fever cases. CONCLUSION: In this survey, the majority of fever and diarrhea
      patients presented first to private practitioners and not to drug vendors or the
      public sector. Successful passive surveillance of febrile or diarrheal illness in
      these communities has to integrate private practitioners.

PMID- 16624185
TI  - Determination of gestational age transverse cerebellar diameter in third
      trimester of pregnancy.
AB  - OBJECTIVE: To assess the usefulness of transverse cerebellar diameter (TCD) as an
      independent parameter for gestational age assessment in third trimester of
      pregnancy. DESIGN: An observational study. PLACE AND DURATION OF STUDY:
      Diagnostic Radiology Department, PNS Shifa, Karachi between April 2002 to July
      2004. PATIENTS AND METHODS: This study was performed on patients between 26-38
      weeks of gestation with normal pregnancy. Grey scale antenatal ultrasonography
      was done with 3.5 MHz probe to measure fetal transverse cerebellar diameter and
      was correlated with gestational age in weeks. These cases were followed
      progressively at different periods of gestation throughout the pregnancy.
      Collected data was converted into variables which were analyzed by SPSS version
      10, descriptive statistics included mean +/- standard deviation which were
      computed for TCD and other fetal biometry parameters. RESULTS: Transverse
      cerebellar diameter varied in a linear fashion in third trimester, while
      transverse cerebellar diameter/abdominal circumference (TCD/AC) ratio remained
      constant in second half of pregnancy. All the parameters were expressed by
      regression equations and correlation coefficients were found to be statistically
      significant (r=0.99 for TCD, r=0.98 for TCD/AC all p<0.0001). CONCLUSION: This
      study signifies that transverse cerebellar diameter and TCD/AC ratio on serial
      sonography give an accurate idea of gestational age. Cases with intrauterine
      growth restriction can be diagnosed if local, nomogram can be prepared for
      different ethnic groups.

PMID- 16624186
TI  - Mass casualty management after a suicidal terrorist attack on a religious
      procession in Quetta, Pakistan.
AB  - OBJECTIVE: To determine the effectiveness of hospital management, considering
      triage system, hospital staff response, medical resources availability, and
      surgical management depending upon the nature and pattern of injuries in a mass
      casualty incident. DESIGN: Descriptive. PLACE AND DURATION OF STUDY: Combined
      Military Hospital, Quetta, Pakistan in March 2004. PATIENTS AND METHODS: All
      injured by gunshot or blast in a terrorist attack and reported to the hospital
      were included in this study. Patients were triaged by the triage team using
      "triage sieve" into priority I, II, III, and IV. Priority I patients were further
      triaged by using "trauma index" to prioritize for surgery. Phase I included life
      saving, Phase II limb saving surgery and Phase III for debridement. All data was
      recorded and analyzed. RESULTS: Hospital received 161 casualties among whom 20
      were brought in dead, and 141 patients were admitted to the hospital. Mean age
      was 26.63 +/- 13.97. The cases were categorized as Priority-I 22.7%, Priority-II
      14.72%, Priority-III 50.31% and Priority-IV 12.27%. Maximum casualties reached
      within the first 2 hours. Eighty-eight patients had pre-dominantly splinter
      injuries and 53 patients had dominantly gunshot wound injuries. In priority I,
      the trauma index was 15.55 +/- 5.74. Six patients having trauma index 20 or above
      could not even be resuscitated. Seventy five percent of staff reported to the
      hospital within 15 minutes. Only 30% of reserve medical store was consumed. Total
      management cost to the hospital was Rs. 362,1856/- (British Pounds approx 32,052/
      .) calculated by the hospital rates for treatment of non-entitled patients. Death
      rate in hospital survivors was 4%. CONCLUSION: Mass casualty management in a
      terrorist act requires prompt hospital response, appropriate triage, efficient
      surgical approach, and dedicated postoperative care. A good response can help to
      decrease mortality rate in salvageable injuries.

PMID- 16624187
TI  - The impact of four-wheel drives on traffic disability and deaths compared to
      passenger cars.
AB  - OBJECTIVE: The aim of this study was to examine the pattern of injuries resulting
      from road traffic crashes involving four wheel drives (4WD) vehicles and
      passenger cars in the United Arab Emirates (UAE). DESIGN: Descriptive study.
      PLACE AND DURATION OF STUDY: Al-Ain and Tawam Hospital, UAE, during a period from
      1st January to 31st December 2000. PATIENTS AND METHODS: A questionnaire was
      created and filled out concerning: sociodemographic information; data about
      driving behavior and attitude which included driving experience, adherence to
      traffic laws (including speed limits and wearing seat belt), driving habits, and
      assessment of sustained injury was performed according to the Abbreviated Injury
      Score (AIS). RESULTS: A total of 1157 motor vehicle crashes related casualty
      patients were hospitalized during the year 2000. Of these total patients, 495
      victims (42.8%) were involved with 4WDs road traffic crashes related injuries and
      72.9% of them required hospitalization. Of these, 76.8% were males, 60.7% were
      non-UAE nationals. The head injury was more common in those who had crashes from
      4WD vehicles (45.6%) than those who had crashes from small cars (37.3%).
      Abbreviated injury scare showed that four wheelers caused more severe (9.1%),
      serious (10.3%), critical (8.3%) and moderate injuries (13.9%). A significant
      higher risk was observed for speed violations (OR=2.06; 95% CI=1.55 - 2.76,
      p<0.001) property damage (OR=1.54; 95% CI=1.07-2.22, p<0.014) and pedestrian
      accident (OR=2.09; 95% CI=1.46-2.99, p<0.001). CONCLUSION: The present study
      findings indicated that nearly half of the road traffic crashes were involved
      with 4WD vehicles and that most of the injured individuals were pedestrian and
      younger drivers. Reduction in motor vehicle injuries and deaths represents a
      major public health success.

PMID- 16624188
TI  - Health seeking behavior of couples with secondary infertility.
AB  - OBJECTIVE: To determine the factors affecting the health-seeking behavior of
      couples with secondary infertility in Karachi. DESIGN: A descriptive case series.
      PLACE AND DURATION OF STUDY: The data was collected from women attending
      infertility clinics in five tertiary care hospitals in Karachi from March to June
      2003. PATIENTS AND METHODS: All currently married women, between the age of 15-35
      years, with at least one previous conception, irrespective of outcome, attending
      an infertility clinic and consenting to participate in the study, were included.
      Women with corrective surgery on vagina and uterus, and cases of primary
      infertility, were excluded. Multiple logistic regression models were used to
      determine the association of various factors, affecting the health-seeking
      behavior, with statistical significance set at p < 0.05 for the covariates and
      the interaction terms between various factors. RESULTS: The women consulted
      multiple health care providers for treatment of secondary infertility. The main
      reasons for seeking treatment were couple s wish (54.2%), family pressure (22.6%)
      and want of a son by husbands or in-laws (20.4%). The most commonly sought
      providers were physicians (74.7%), Traditional Birth Attendants (TBA, 39.5%),
      Spiritual healers (26%), Hakeems (23%) and Homeopaths (17.2%). Most of the women
      who consulted non-physicians were illiterate (69.4%) as compared to those who
      consulted a physician (37.8%, p-value = 0.00). The non-physicians were more
      commonly consulted by women belonging to low socioeconomic group. The
      posttreatment complications were more common among women who consulted non
      physicians. CONCLUSION: Pressure from husbands and in-laws compels women for
      consulting multiple providers. Health seeking behavior for infertility is
      affected by the literacy and socioeconomic status of the women.

PMID- 16624190
TI  - Chicken pox associated thrombocytopenia in adults.
AB  - OBJECTIVE: To determine the frequency and magnitude of thrombocytopenia
      associated with chicken pox in adults. DESIGN: Observational descriptive study.
      PLACE AND DURATION OF STUDY: Combined Military Hospital, Attock, from July 2003
      to June 2004. PATIENTS AND METHODS: All patients of age 15 years and above with
      history of fever, followed by appearance of the typical vesicular chicken pox
      rash, were inducted after informed consent. Two milliliters of whole blood was
      collected on day 1 of admission, and blood counts were performed. Patients were
      admitted and given 800 mg oral acyclovir, 5 times/day, for 7 days, in addition to
      symptomatic treatment. Patients were followed till 8 weeks. RESULTS: A total of
      410 patients of chicken pox were received, out of which 270 were included. Age of
      patients ranged between 15 and 40 years with median age of 21 years. Platelet
      count on the day of admission ranged between 29 x 10(9)/L to 513 x 10(9)/L, mean
      platelet count 178 x 10(9)/L. Platelet count < 150 x 10(9)/L was detected in
      80/270 (30%) patients. Platelet count in thrombocytopenia patients was from 29 x
      10(9)/L to 149 x 10(9)/L with mean 121 x 10(9)/L. Thrombocytopenia recovered
      within 02 weeks in 78/80 (97%) patients. In 2 patients, thrombocytopenia
      recovered in 3 weeks. None of the patients developed purpuric spots, ecchymosis
      or bleeding manifestations. CONCLUSION: Thrombocytopenia in chicken pox is a
      common entity. Platelet count remains above 25 x 10(9) /L, which is usually not
      associated with bleeding manifestations. None of the patients in this series
      developed purpura. No specific pattern of total leukocyte counts was predictive
      of the progression or regression in platelet count.

PMID- 16624189
TI  - Median survival time of patients after transcatheter chemo-embolization for
      hepatocellular carcinoma.
AB  - OBJECTIVE: To determine the effect on survival after transarterial
      chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma
      (HCC). DESIGN: Longitudinal cohort study. PLACE AND DURATION OF STUDY: Radiology
      Department, The Aga Khan University Hospital, Stadium Road, Karachi, from
      December 1997 to September 2005. PATIENTS AND METHODS: Patients undergoing TACE
      procedure for HCC were prospectively followed. Fortythree patients were enrolled
      from December 1997 to March 2003 in the study and subjected to chemoembolization
      therapy. Eight out of 43 patients were excluded from the study, who lost to
      follow-up. All the patients were followed till their death. Median and mean
      survival were calculated. RESULTS: The median survival of these 35 patients was
      410 days (13.6 months), with 95% confidence interval (236 days lower bound and
      536 days upper bound). Mean survival time was 603 days (20.1 months) with 95%
      confidence interval (394 days lower bound and 812 days upper bound). There was
      significant difference in mean survival time (in days) by Child s Pugh class
      (chi(2) = 12.384; df=2, p-value=0.002). CONCLUSION: The study showed that TACE is
      an effective palliative treatment. TACE increases the median survival time.

PMID- 16624191
TI  - Frequency and risk factors of asymptomatic bacteriuria during pregnancy.
AB  - OBJECTIVE: To determine the frequency and risk factors of asymptomatic
      bacteriuria during pregnancy. DESIGN: Cross-sectional study. PLACE AND DURATION
      OF STUDY: Satellite Town and Behari Colony, Bahawalpur from October 2001 to March
      2002. PATIENTS AND METHODS: There were 3000 houses in Satellite Town and Behari
      Colony, Bahawalpur. Taking 40% of total, 1200 houses were selected by systemic
      random sampling. Pregnant residents of these houses were included in the study.
      Data collected was coded, computed and analyzed on SPSS version 10. Frequencies
      were runned and chi-square test was used as test of significance. RESULTS: Five
      hundred and eighty women, fulfilling the inclusion criteria, were interviewed and
      tested for bacteriuria. Out of them, 4% were below 20 years, 4.6% were between 20
      30 years and 5.4% women aged above 30 years (p=0.103). Regarding parity 3.18 % of
      primigravidae and 6.04 % multigravida had bacteriuria (p=0.0039). Regarding
      socioeconomic status, 6.45% from lower class and 2.5% from middle and upper
      middle class were the sufferer (p=0.0039). Prevalence was 6.64% among uneducated
      and 3.06% among educated women (p=0.0039). As for past history, 35.7% of women
      had an episode previously (p=0.001). No association was found with anaemia.
      CONCLUSION: Asymptomatic bacteriuria is a common infection during pregnancy,
      having strong association with multiparity, lower socioeconomic status and
      illiteracy.

PMID- 16624192
TI  - Efficacy of dinoprostone, intracervical foleys and misoprostol in labor
      induction.
AB  - OBJECTIVE: To compare the efficacy for Dinoprostone, intracervical foleys and
      misoprostol in labor trial regarding effects on cervical ripening, mode of
      delivery, induction to delivery interval and maternal complications i.e.
      tachysystole and postpartum haemorrhage. DESIGN: Randomized clinical trial. PLACE
      AND DURATION OF STUDY: Hamdard University Hospital and Patel Hospital between
      July 2004-June 2005. PATIENTS AND METHODS: Randomized trial was conducted such
      that group-A received Dinoprostone at 6 hourly intervals upto two doses. Group-B
      was induced with intracervical foley catheter. Group-C received 50 micro g oral
      misoprostol 4 hourly to a maximum of four doses. Cervical ripening, induction to
      delivery time interval, mode of delivery and maternal morbidity were main outcome
      measures. Test of proportions was used to compare the significance between the
      managements. RESULTS: In 226 cases, 219 (97%) were successfully induced while
      7(3%) did not respond the labour induction. The rates of caesarean section in
      dinoprostone, intracervical foley and misoprostol were 14.7%, 14.1% and 12.3%,
      respectively, however, this difference was insignificant among three groups
      (p=0.911). Rate of earlier response (< or = 12 hours) to labor induction among
      three groups was insignificant (3.8% vs 4% and 13.7% respectively, p=0.125).
      Marginal significance of higher rate of complications was observed in those
      patients who were given misoprostol (p=0.08). CONCLUSION: In this series, all
      three agents were equally effective in terms of cervical ripening, induction
      delivery interval, mode of delivery and maternal complications.

PMID- 16624193
TI  - Mutation of p53 in skin papilloma and tubular breast adenoma of albino mice.
AB  - OBJECTIVE: To determine the mutation of p53 in chemically induced carcinogenesis
      on albino mice in skin papilloma and tubular adenoma breast by
      immunohistochemistry. DESIGN: An experimental study. PLACE AND DURATION OF STUDY:
      The animal house of Postgraduate Medical Institute and Pathology Department of
      King Edward Medical College University, Lahore, for the duration of 20 weeks,
      from 15 February, 2004 to 15 July, 2004. SUBJECTS AND METHODS: Twenty five albino
      mice (male and female) were selected for a study on chemical carcinogenesis.
      These animals were divided into five groups (A-E), five animals in each. DMBA
      (Dimethylebenz[a] Anthracene) and TPA (Tetradecanoyl-phorbal-13-Acetic Acid)
      [chemical carcinogens] were given to produce the tumors and mutation of p53
      expression was evaluated on the tumors appearing during this period of
      carcinogenesis. Squamous cell papillomas and tubular adenoma breast were selected
      for this study. RESULTS: All the papillomas showed faint reactivity for
      immunomarker p53, while tubular adenomas were nonreactive. CONCLUSION: The
      results of this study show that p-53 is a marker for premalignant lesions and
      helps in selecting patients for constant monitoring, upon the clinical
      verification of these results.

PMID- 16624194
TI  - Modification of Mathieu procedure to repair anterior hypospadias.
AB  - OBJECTIVE: To assess the results of one-stage repair of anterior hypospadias
      using modified Mathieu procedure. DESIGN: An interventional study. PLACE AND
      DURATION OF STUDY: Department of Paediatric Surgery, Dow Medical College and
      Civil Hospital Karachi, from September 1997 to December 2003. PATIENTS AND
      METHODS: All the patients with anterior hypospadias without or with minimal
      chordee were included. Patients with hypoplastic urethra or re-do surgery were
      excluded. Modified Mathieu repair was performed in all cases. The modifications
      used were interrupted inverting sutures of 5/0 polyglycolic acid for
      urethroplasty; neourethra covering with subcutaneous (dartos) pedicle flap,
      developed from the preputial or penile shaft skin and dorsal / anterior meatotomy
      for meatal stenosis. RESULTS: A total of 69 patients with anterior hypospadias
      were operated using modified Mathieu s repair. Only two patients (2.89%)
      developed urethrocutaneous fistula. Five patients developed partial
      devitalisation of the covering skin while one patient had complete breakdown.
      CONCLUSION: Modified Mathieu s procedure is an effective method, to repair the
      anterior hypospadias without or with minimal chordee.

PMID- 16624195
TI  - Acute respiratory failure in Pakistani patients: risk factors associated with
      mortality.
AB  - OBJECTIVE: To assess the outcome and risk factors associated with mortality in
      patients with acute respiratory failure (ARF). DESIGN: Observational study. PLACE
      AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, between January
      1997 and June 2001. PATIENTS AND METHODS: All adult patients admitted with a
      medical cause of acute respiratory failure were reviewed. The primary outcome
      measure was mortality and secondary outcome measures were factors associated with
      mortality in ARF. Multiple logistic regression analysis was used to identify the
      independent risk factors for mortality. RESULTS: A total of 270 patients were
      admitted with ARF. Hypercapnic respiratory failure was seen in 186 (69%) and
      hypoxemic in 84 (31%) cases. Pneumonia and COPD exacerbation were the most common
      underlying causes of ARF. Ventilator support was required in 93 (34.4%) patients.
      Hospital mortality was 28%. Chronic renal failure, malignancy, hypokalemia,
      severe acidosis (pH <7.25) septicemia and ARDS independently correlated with
      mortality. Mortality rate increased sharply (84%) with the presence of three or
      more risk factors. CONCLUSION: Acute respiratory failure has a high mortality
      rate (28%). Development of ARDS or septicemia was associated with high mortality.
      Presence of more than one risk factor significantly increased the mortality rate.

PMID- 16624196
TI  - Evaluatioin paradigms in medical education.
AB  - Medical education is regularly challenged with new and innovative ideas in the
      field of curricula, teaching learning processes and assessment. Evaluation of
      these approaches and techniques provide vital information regarding their
      subsequent use and application to enhance the quality of learning experiences for
      students. Therefore, it is essentially important to choose an evaluation
      approach/model that provide meaningful and valid information to concerned
      stakeholders. Here two major paradigm of evaluation i.e. scientific and
      naturalistic are discussed emphasizing on their use, strengths and limitations.
      It is concluded that no single paradigm is superior to other and it is finally
      left to the evaluator for making the ultimate choice depending on the purpose and
      questions that need to be answered through evaluation.

PMID- 16624197
TI  - Scar leishmaniasis.
AB  - A large spectrum of clinical presentations of cutaneous leishmaniasis (CL) have
      been reported including a scar presentation in many chronic cases. We report here
      a case where CL developed in a scar of healed lesion of tuberculoid leprosy.
      Initially, it was suspected as a relapse or reaction of the previous disease, but
      on histopathology, it proved to be a new disease (CL). On anti-leishmaniasis
      treatment, lesion healed satisfactorily in about a month time.

PMID- 16624198
TI  - Granuloma faciale -- an unusual presentation.
AB  - Granuloma faciale is a rare skin disorder, characterized by asymptomatic
      cutaneous nodules on the face without any systemic manifestations. The disorder
      mainly affects middle-aged Caucasian males. One such case occurring in a young
      unmarried lady of "Pathan" descent is presented here. The presentation was
      unusual due to the history of frequent swelling, redness and heat in her nodules
      without any known stimuli and spontaneous regression of the nodules to the
      original size in a few hours. The patient was treated with a combination of
      cryotherapy and intralesional corticosteroids with excellent results.

PMID- 16624199
TI  - Non-dysraphic intramedullary spinal cord lipoma.
AB  - True intramedullary spinal cord lipomas are extremely rare. Two cases of
      intramedullary spinal cord lipoma are presented. The patients did not exhibit any
      form of spinal dysraphism. The patients presented with gait difficulty, upper
      limb weakness, sphincter disturbance, dysesthesias and neck pain. The tumors were
      removed sub-totally and the neurological grade improved postoperatively in one of
      the patients.

PMID- 16624200
TI  - Bilateral suppurative parotitis in a newborn.
AB  - Suppuration occurring in inflamed parotid glands is an uncommon observation in
      the neonatal age group. This case report describes a male neonate, 12 days of
      age, who presented with high grade fever, irritability, poor feeding and
      bilateral swelling in the parotid region. Workup showed bilateral suppurative
      parotitis. Abscess developed despite antibiotic therapy requiring surgical
      drainage before final recovery.

PMID- 16624201
TI  - Fractured tracheostomy tube in the tracheo-bronchial tree.
AB  - Tracheostomy is a life saving procedure and many a times patients are discharged
      with permanent tracheostomy tubes. However, fracture of tracheostomy tube with
      subsequent migration into the tracheobronchial tree is uncommon and carries the
      potentially fatal risk of respiratory obstruction. In this report, a case of a 6
      year-old boy is presented, who had aspirated a fractured tracheostomy tube which
      had lodged in the left bronchus.

PMID- 16624202
TI  - Ingestion of metallic rods and needles.
AB  - Foreign bodies in gastrointestinal tract (GIT) are not very rare. This case
      describes a patient purposefully swallowing metallic objects. These were five
      iron rods ranging 4-5 inches in length, and two needles. One of the rod
      perforated duodenum and was found in pelvic cavity upon exploration. The rest of
      the rods were in small gut and stomach.

PMID- 16624203
TI  - Primary splenic lymphoma.
AB  - A middle-aged lady presented with fever and splenomegaly and had been
      provisionally treated for malaria, typhoid and tuberculosis. Diagnostic
      splenectomy was performed which revealed diffuse large cell lymphoma, B type,
      localized to spleen. Patient had remission of disease after splenectomy.

PMID- 16624204
TI  - Primary repair of an esophageal rupture using pleural flap.
AB  - Esophageal perforation remains an important thoracic emergency. Aggressive
      operative therapy remains the mainstay for treatment. A case of esophageal
      perforation, consequent upon impacted food bolus, is presented. An 80 years old
      female, with multiple comorbidities, presented with dysphagia and right sided
      chest pain, who had a distal esophageal tear, secondary to accidental meat ball
      ingestion. Rigid esophagoscopy showed complete occlusion of the distal esophagus
      with a meat ball. Right thoracotomy was performed, which showed perforated
      esophagus with large meat ball protruding from it. Endoscopic removal of the food
      particles was done, and the rupture was repaired using a pleural flap. The entire
      postoperative stay was uneventful and the patient was discharged on the ninth
      post-operative day.

PMID- 16624205
TI  - Homocysteine levels in Pakistanis with myocardial infarction and normal healthy
      subjects.

PMID- 16624206
TI  - Association of smoking with lymph nodes metastasis in early stages of squamous
      cell carcinoma of tongue.

PMID- 16624207
TI  - Frequency of HIV infection amongst hospital visitors at Tubmanburg Town in
      Liberia.

PMID- 16624208
TI  - Healing powers among doctors: is there a role for mysticism?

PMID- 16624209
TI  - Esophageal cancer in East and West: a different disease, pattern or population?

PMID- 16624210
TI  - Prospective CT scan evaluation of hindfoot nonunions treated with revision
      surgery and low-intensity ultrasound stimulation.
AB  - BACKGROUND: The reported fusion rates of revision arthrodesis for hindfoot
      nonunions are relatively low compared to primary procedures. Exogenous ultrasound
      has been shown to accelerate the healing process of acute fractures and fracture
      nonunions but has not been previously evaluated for the treatment of hindfoot
      pseudarthroses. The purpose of this study was to evaluate the clinical and
      radiographic outcomes of revision hindfoot arthrodeses treated with postoperative
      low-intensity ultrasound. METHODS: Thirteen patients (13 feet) with established
      hindfoot nonunions were treated with revision arthrodesis and adjunctive
      postoperative low-intensity ultrasound. The patients were prospectively evaluated
      with hindfoot American Orthopaedic Foot Ankle Society (AOFAS) and pain visual
      analog scores, subjective satisfaction surveys, and serial radiographs. All
      patients underwent postoperative CT to evaluate the fusion mass, which was
      quantitated using a novel system. The mean follow-up from revision surgery was
      16.3 (range 12 to 25) months. The 10 subtalar and three triple revision
      arthrodeses comprised a total of 19 joints. RESULTS: Based on the CT scans and
      the grading system devised, there was one nonunion (isolated subtalar revision),
      five partial unions, and 13 complete unions. The 10 isolated subtalar revision
      arthrodeses demonstrated a mean fusion ratio of 65.1% (range 14% to 100%).
      Excluding the one nonunion, the average fusion ratio for the subtalar revisions
      was 77.3%. The mean hindfoot AOFAS score improved significantly (p < 0.005) from
      45.3 (range 18 to 65) preoperatively to 72.3 (range 47 to 92) postoperatively out
      of 94 possible points. There was a significant (p < 0.005) decrease in the pain
      visual analog scale (VAS) from a preoperative value of 7.7 (range 4 to 10) to a
      postoperative value of 2.5 (range 0 to 6). There was a weak inverse correlation
      between the fusion percentages and the pain VAS scores (r = -0.26) and a weak
      correlation (r = 0.29) between the fusion percentages and the final AOFAS scores.
      CONCLUSIONS: When used to evaluate hindfoot arthrodeses, plain radiographs may be
      misleading. CT provides a more accurate assessment of the healing, and we have
      devised a new system to quantitate the fusion mass. Postoperative low-intensity
      ultrasound is easy to apply and administer, with no identifiable risks or
      contraindications. Although this modality may facilitate the fusion process, we
      cannot definitely conclude the specific relative value of low-intensity
      ultrasound because this was not a controlled series.

PMID- 16624211
TI  - The relationship between tears of the peroneus brevis tendon and the distal
      extent of its muscle belly: an MRI study.
AB  - BACKGROUND: Anomalous distal insertion of the peroneus brevis muscle belly has
      been implicated as a possible etiology of tears of the peroneus brevis tendon.
      The purpose of this study was to assess whether patients with operatively
      confirmed tears of the peroneus brevis tendons have a more distally located
      musculotendinous junction. METHODS: A retrospective review was done to identify
      all patients in whom direct inspection of the peroneal tendons was done between
      1999 and 2004. The operative reports were evaluated, and all in whom a peroneal
      tendon tear was confirmed were included in the study group, Group I (29
      patients). Group II represented an operative control group and consisted of all
      patients who had operative inspection of the peroneal tendons but did not have a
      tear (30 patients). Group III represented a radiographic control group and
      consisted of patients who had MRI of the ankle for reasons unrelated to lateral
      ankle symptoms (30 patients). For each patient, the vertical distance from the
      musculotendinous junction of the peroneus brevis tendon to the tip of the fibula
      was measured on sagittal MRI. The role of gender also was examined. The average
      distance between the musculotendinous junction of the peroneus brevis tendon to
      the distal fibula was calculated solely for men and women in all three groups.
      Statistical comparison of the groups was performed using the Mann-Whitney test.
      Interobserver reliability was determined by calculating Cronbach's Alpha
      coefficient. RESULTS: The average distance from the musculotendinous junction to
      the tip of the fibula was 33.1 cm, 41.2 cm, and 46.3 cm in Groups I, II, and III,
      respectively. The average distance in Group I was statistically significantly
      lower than the average distance in both Groups II and III (p < 0.05).
      Interestingly, the difference in the distance between Groups II and III also was
      statistically significant (p < 0.05). The average distances in both men and women
      were statistically significantly different (p < 0.05) among the three groups.
      CONCLUSION: It has been hypothesized that tears of the peroneus brevis tendon
      result from distal insertion of the peroneus brevis muscle belly. This study
      provides radiographic support for this hypothesis.

PMID- 16624212
TI  - Differentiating clinical and radiographic features of enchondroma and secondary
      chondrosarcoma in the foot.
AB  - BACKGROUND: Enchondroma is the most common benign tumor of the bones of the foot.
      Chondrosarcoma in this area is relatively rare with malignant transformation from
      enchondroma occurring rarely. In contrast to similar tumors in the appendicular
      skeleton, it is difficult to distinguish between these two tumors when they occur
      in the foot. METHODS: We reviewed the medical records and radiographs of all
      patients with enchondroma and chondrosarcoma arising from enchondroma (secondary
      chondrosarcoma) from the radiologic archives at the Armed Forces Institute of
      Pathology (AFIP) and identified those patients with tumors involving the bones of
      the foot. There were 755 patients with enchondroma of which 34 (4.8%) involved
      the foot; there were 340 patients with secondary chondrosarcoma and 14 (4.1%)
      involved the foot. We compared clinical and radiographic features of both these
      lesions. We also compared interobserver differences not only for diagnosis but
      also for the presence of scalloping, fracture, cortical destruction, and
      mineralized matrix. RESULTS: Size and location were statistically significant
      variables differentiating the two tumors (p = 0.03). Enchondromas had a mean size
      of 2.7 cm(2). Lesions that occurred in the hindfoot and midfoot were more likely
      to be malignant compared to those in the forefoot. In comparing interobserver
      reliability, most disagreement occurred regarding the presence or absence of
      matrix with the examiners concurring only 51% of the time. With regard to
      diagnosis, the examiners' accuracy was 71% and 80%. Their accuracy increased only
      to 83% when they agreed. CONCLUSION: Our findings suggest that it is difficult to
      differentiate enchondroma from secondary chondrosarcoma in the foot. Concern for
      malignant change is warranted for cartilage bone tumors of the foot if they
      exceed 5 cm(2), or if they arise in the midfoot or hindfoot. In these cases, we
      recommend either biopsy or close clinical followup.

PMID- 16624213
TI  - Surgical management of insertional calcific achilles tendinosis with a central
      tendon splitting approach.
AB  - BACKGROUND: Insertional calcific Achilles tendinosis is a painful, frequently
      disabling condition. Numerous operative approaches for this problem have been
      described. This study evaluated the outcome of a central tendon splitting
      approach. METHODS: Twenty-two patients were evaluated after a central tendon
      splitting approach for persistent insertional calcific Achilles tendinosis.
      Followup averaged 34 (11 to 64) months. Suture anchors were routinely used to
      augment the tendon insertion after debridement. An American Orthopaedic Foot and
      Ankle Society (AOFAS) hindfoot score, shoewear comfort, and return to work were
      evaluated. A paired t-test was used to evaluate the results. RESULTS: Pain
      significantly improved from 7 points preoperatively to 33 points postoperatively
      (p < 0.001). Function improved significantly from 36 points to 46 points (p <
      0.001). The ankle-hindfoot score improved from 53 points to 89 points (p <
      0.001). Age older or younger than 50 years did not affect outcome. CONCLUSION: A
      central tendon splitting approach yielded good relief of pain with improved
      function, shoewear, and ability to work without painful postoperative scars.

PMID- 16624214
TI  - Interobserver and intraobserver reliability of two classification systems for
      intra-articular calcaneal fractures.
AB  - BACKGROUND: For a fracture classification to be useful it must provide prognostic
      significance, interobserver reliability, and intraobserver reproducibility. Most
      studies have found reliability and reproducibility to be poor for fracture
      classification schemes. The purpose of this study was to evaluate the
      interobserver and intraobserver reliability of the Sanders and Crosby-Fitzgibbons
      classification systems, two commonly used methods for classifying intra-articular
      calcaneal fractures. METHODS: Twenty-five CT scans of intra-articular calcaneal
      fractures occurring at one trauma center were reviewed. The CT images were
      presented to eight observers (two orthopaedic surgery chief residents, two foot
      and ankle fellows, two fellowship-trained orthopaedic trauma surgeons, and two
      fellowship-trained foot and ankle surgeons) on two separate occasions 8 weeks
      apart. On each viewing, observers were asked to classify the fractures according
      to both the Sanders and Crosby-Fitzgibbons systems. Interobserver reliability and
      intraobserver reproducibility were assessed with computer-generated kappa
      statistics (SAS software; SAS Institute Inc., Cary, North Carolina). RESULTS:
      Total unanimity (eight of eight observers assigned the same fracture
      classification) was achieved only 24% (six of 25) of the time with the Sanders
      system and 36% (nine of 25) of the time with the Crosby-Fitzgibbons scheme.
      Interobserver reliability for the Sanders classification method reached a
      moderate (kappa = 0.48, 0.50) level of agreement, when the subclasses were
      included. The agreement level increased but remained in the moderate (kappa =
      0.55, 0.55) range when the subclasses were excluded. Interobserver agreement
      reached a substantial (kappa = 0.63, 0.63) level with the Crosby-Fitzgibbons
      system. Intraobserver reproducibility was better for both schemes. The Sanders
      system with subclasses included reached moderate (kappa = 0.57) agreement, while
      ignoring the subclasses brought agreement into the substantial (kappa = 0.77)
      range. The overall intraobserver agreement was substantial (kappa = 0.74) for the
      Crosby-Fitzgibbons system. CONCLUSIONS: Although intraobserver kappa values
      reached substantial levels and the Crosby-Fitzgibbons system generally showed
      greater agreement, we were unable to demonstrate excellent interobserver or
      intraobserver reliability with either classification scheme. While a system with
      perfect agreement would be impossible, our results indicate that these
      classifications lack the reproducibility to be considered ideal.

PMID- 16624215
TI  - Results and outcomes after operative treatment of high-energy tibial plafond
      fractures.
AB  - BACKGROUND: The purposes of this study were to evaluate the clinical and
      radiographic results and the functional outcomes after operative treatment of
      tibial plafond fractures treated with internal or external fixation. METHODS: A
      retrospective review identified 76 patients with 79 fractures (OTA 43-B or 43-C)
      of the tibial plafond. Their average age was 45 years. Twenty-one fractures (27%)
      were open, and 43 (54%) were type 43-C3. Five were type 43-B1, four were 43-B2,
      two were 43-B3, 15 were 43-C1, and 10 were 43-C2. Patients were treated with open
      reduction and internal fixation (ORIF) (n = 63) or limited open articular
      reduction and wire ring external fixation (EF) (n = 16). Tibial fixation was
      performed at a mean of 7.6 days after injury, with staged reconstruction in 56
      fractures (71%). Bone graft was used initially in 32 fractures (41%). Early and
      late complications, secondary procedures, and radiographic evidence of post
      traumatic arthritis were evaluated. Foot Function Index (FFI) and Musculoskeletal
      Function Assessment (MFA) questionnaires were administered. RESULTS: Seventy-nine
      fractures were followed clinically and radiographically for a mean of 26 (range
      24 to 38) months, and 33 patients completed outcomes questionnaires at a mean of
      98 months after surgery. Early complications included two superficial wound
      problems and three deep infections. Late complications included two nonunions and
      four malunions. Thirty-one fractures (39%) developed post-traumatic arthritis.
      Complications occurred after six of 21 open fractures and after 11 of 43 type C3
      fractures (p = 0.007). Patients treated with EF more frequently had type C3
      fractures (88% versus 46%, p = 0.004) compared with patients treated with ORIF.
      The EF patients developed more complications (six of 16, p = 0.007) and post
      traumatic arthritis (11 of 16, p = 0.01) when compared with ORIF. Patients
      treated with EF (88% were type C3 fractures) had lower FFI and MFA scores. The
      greatest impairment in outcome was noted after type C3 fractures, regardless of
      the method of treatment. CONCLUSIONS: Tibial plafond fractures are difficult to
      manage and may have serious complications. We identified more complications, more
      secondary procedures, and worse outcomes in patients with articular and
      metaphyseal comminution (type C3). ORIF was associated with fewer complications
      and less post-traumatic arthritis when compared to EF, possibly reflecting a
      selection bias for open injuries and more severely comminuted fractures to be
      managed with EF. ORIF with appropriate soft tissue handling resulted in
      acceptable results in most patients. Severely damaged soft tissues and highly
      comminuted C3 fractures may be safely treated with EF. Loss of function and
      progression to post-traumatic arthritis are common after tibial plafond
      fractures. Assessment of long-term results and the efficacy of additional
      reconstructive procedures will refine the treatment algorithms for these
      fractures.

PMID- 16624216
TI  - Correction of neglected clubfoot using the Ilizarov external fixator.
AB  - BACKGROUND: This study was conducted to evaluate the corrective capability of the
      Ilizarov external fixator in the treatment of neglected clubfoot. METHODS: Thirty
      patients (38 feet) with a mean age of 19 (5 to 39) years with severe deformities
      and stiff feet associated with neglected clubfoot were studied. A limited soft
      tissue dissection, Achilles tenotomy, and plantar fasciotomy were done.
      Progressive correction of the deformities was achieved through a standard setting
      of the Ilizarov external fixator. The device was used for 16 weeks, on average,
      and after removal a short-leg walking cast was used for an additional 6 weeks,
      followed by an ankle-foot orthosis (AFO) for 6 months. RESULTS: The final outcome
      was scored as good (complete correction and no pain); fair (partial correction
      with plantigrade foot and occasional pain); or poor (nonplantigrade foot and
      continuous pain during walking). After a mean followup of 58 (range 12 to 107)
      months, the results were good in 30 feet (78.9%); fair in three feet (7.9%); and
      poor in five feet (13.2%). Early complications were a distal tibial fracture in
      one foot, dislocation of the first metatarsophalangeal joint in one foot, and
      arterial damage that resulted in amputation of the toes in one foot. Recurrence
      of the deformity was found in 19 feet (50%): 11 minor, three mild, and five
      severe. Spontaneous ankylosis developed in 28 feet (73.7%). Nine feet (23.7%)
      required arthrodesis for symptomatic arthritis of the ankle or midfoot and
      deformity that could not be treated with orthoses. CONCLUSION: The Ilizarov
      external fixator allows simultaneous correction of all the severe foot
      deformities associated with neglected clubfoot with minimal surgery, reducing
      risks of cutaneous or neurovascular complications and avoiding excessive
      shortening of the foot. Even in those patients in whom final corrective
      arthrodesis is necessary, this may be carried out with minimal bone resection,
      since the severe deformities of the foot and ankle have been corrected.

PMID- 16624217
TI  - Quality of life of adults with unhealed and healed diabetic foot ulcers.
AB  - BACKGROUND: Diabetic foot ulcers cause major treatment morbidity and cost of
      care. This study evaluated quality of life in patients with unhealed and healed
      diabetic foot ulcers. METHODS: This was a cross-sectional study of adult diabetic
      patients (age 45 years or older) treated in a tertiary care foot clinic who had
      foot ulcers within the preceding 2 years. Patients with other diabetic
      complications or conditions that would potentially affect quality of life were
      excluded. Two patient groups of comparable age, gender distribution, and duration
      of diabetes were studied: 57 patients with unhealed ulcers (minimum duration, 6
      months) and 47 patients with healed ulcers. Telephone interviews were done using
      the Short Form 12 (SF-12) (both groups) and a Cardiff Wound Impact Scale (CWIS)
      (unhealed ulcer group). RESULTS: The mean SF-12 Physical Component Summary score
      was significantly lower for the group with unhealed ulcers (unhealed, 35 +/- 8
      points; healed, 39 +/- 10 points; p = 0.04); these scores for both groups were
      significantly lower than published Short Form 36 (SF-36) scores for general,
      diabetic, and hypertensive populations. The mean SF-12 Mental Component Summary
      scores of the groups did not differ significantly from each other or from
      published population scores. CWIS responses showed that patients with unhealed
      ulcers were frustrated with healing and had anxiety about the wounds, resulting
      in marked negative impact on the average Well-being Component Score (35 +/- 6
      points). CONCLUSIONS: Individuals with diabetic foot ulcers experience profound
      compromise of physical quality of life, which is worse in those with unhealed
      ulcers.

PMID- 16624218
TI  - Unloading mechanism in the total contact cast.
AB  - BACKGROUND: The effectiveness of total contact casts is postulated to be due to
      the reduction of plantar pressure. We investigated plantar loads to evaluate the
      mechanism by which total contact casts off-load the plantar surface of the foot
      to determine if it is the intimate molding of the weightbearing plantar surface
      or if a below-knee cast is necessary. METHODS: Plantar pressures and forces in a
      total contact cast (TCC) were recorded in 12 healthy subjects, using the Pedar
      (Novel GmbH, Munich, Germany) pedobarographic system. The measurements were
      repeated after removal of the 'shank' portion of the cast (proximal to malleoli),
      leaving in effect, a well-molded shoe-cast (SC). Measurements included average
      force and peak pressure. All parameters were measured under two different loading
      conditions: single-leg standing balanced on the casted limb and over-ground
      walking. To assess the contribution of calf geometry, the 'calf ratio' was
      calculated by dividing the largest by the smallest circumferences of the calf.
      All parameters were compared between TCC and SC for each subject in each of the
      two conditions. Paired t-tests were used to evaluate significance, which was set
      at a level of p < 0.006 due to the Bonferroni Correction. RESULTS: Removal of the
      shank portion of the TCC significantly increased the average plantar force by 31%
      during walking. The force only increased 9% during standing, which was not
      significant. Peak pressure increased 53% after removal of the shank portion of
      the TCC during walking. Peak pressure was not significantly different during
      standing on one limb. No correlation was found between the calf ratio and the
      magnitude of change in the measured values. CONCLUSIONS: These results help to
      partially explain the widely recognized clinical observation that molded insoles
      and shoes, no matter how well conformed to the foot, do not reduce plantar loads
      as effectively as a total contact cast. The mechanism appears to be a critical
      unloading function of the proximal, 'shank' portion of the cast, presumably due
      to reduction in ankle motion.

PMID- 16624219
TI  - The use of a working model for teaching functional and applied surgical anatomy
      of the subtalar joint.
AB  - BACKGROUND: Some aspects of functional and applied anatomy may be difficult to
      conceptualize if taught by conventional methods. In such situations, alternative
      methods of teaching may need to be adopted. This study was undertaken to evaluate
      whether a working model can facilitate understanding of the functional and
      applied surgical anatomy of the subtalar joint. METHODS: A working model of the
      articulated talus and calcaneus was constructed and used to explain the mechanics
      of motion of the subtalar joint, the rationale of release of structures to
      correct hindfoot deformity in clubfoot, principles of tendon transfers, and the
      rationale of extra-articular subtalar joint arthrodesis. Twenty-four orthopedic
      residents were divided into two groups (A and B). Group A was taught these
      specific concepts of functional and applied anatomy with the help of the model,
      while Group B was taught the same concepts with a written text and diagrams. The
      level of knowledge of both groups was evaluated by a test with multiple-choice
      questions. A week later, Group A was given the text while Group B was shown the
      model. Both groups then answered a questionnaire assessing the value of the model
      in enhancing their understanding of the subject. RESULTS: In the test, the
      performance of students in Group A was better than those in Group B. Students of
      both groups felt that the model gave them a much clearer understanding of the
      functional anatomy of the subtalar joint. CONCLUSIONS: We conclude that this
      simple, inexpensive model is a valuable teaching aid that helps students to
      understand the surgical anatomy of the subtalar joint. CLINICAL RELEVANCE:
      Surgeons can use this model to effectively teach trainees in this field about the
      mechanics and anatomy of the subtalar joint and other relevant applications.

PMID- 16624220
TI  - Posterior ankle pain diagnosed by positional MRI of the ankle: a unique case of
      posterior ankle impingement and osteonecrosis of the talus.

PMID- 16624221
TI  - Symptomatic calcification of the adductor hallucis tendon at the first
      metatarsophalangeal joint: report of two cases.

PMID- 16624222
TI  - Modified bone block distraction arthrodesis of the hallux metatarsophalangeal
      joint.

PMID- 16624223
TI  - Technique tip: posterior blade plate for salvage of failed total ankle
      arthroplasty.

PMID- 16624224
TI  - Current concepts review: acute ruptures of the achilles tendon.

PMID- 16624225
TI  - [Mortality of gastric cancer in Catalonia, Spain: geographical distribution and
      time trends from 1986 to 2000].
AB  - BACKGROUND AND OBJECTIVE: The aims of this study are to describe the time trends
      and the changes in the spatial distribution of stomach cancer mortality by
      gender, in Catalonia, Spain, in the period 1986-2000. MATERIAL AND METHOD: The
      mortality data comes from the Mortality Register for Catalonia at the Health
      Department and the population data from the Institute of Statistics for
      Catalonia. To analyze time trends, a Poisson regression model was adjusted for
      each gender. To analyze the geographical distribution, a Bayesian hierarchical
      model was used. RESULTS: During the period 1986-2000 the number of deaths from
      stomach cancer was 8,627 for males and 5,831 for females. During this period the
      estimated decrease in mortality was 3.13% for males and 3.91% for females. The
      spatial analysis showed the lowest mortality risk areas along the coast while the
      mortality risk increased toward the zones in the interior. This geographical
      pattern is very similar for both sexes but in the lasts years of the period it
      has been fading. CONCLUSIONS: The time trends and the geographical pattern of
      stomach cancer mortality in Catalonia is similar for both sexes and it is
      consistent with the trends observed in other developed countries. This suggests a
      relationship with improved food habits and a better accessibility to health care
      in the areas of higher risk.

PMID- 16624226
TI  - [Validation of 3 equations of coronary risk in diabetic population of a primary
      care center].
AB  - BACKGROUND AND OBJECTIVE: We intended to validate to 10 years 3 equations of
      coronary risk that use the function of original Framingham (Framingham-Anderson
      and Framingham-Wilson) and calibrated for Spanish population (Framingham-REGICOR)
      in diabetic patients type 2. PATIENTS AND METHOD: We included a total of 190
      diabetic patients from a primary care center, without coronary heart disease, in
      whom the coronary risk could be calculated before 1 January 1995. All were
      followed during 10 years. RESULTS: The highest score of cardiovascular risk was
      obtained in the Framingham-Wilson function chart (25.4%) and the lowest in the
      Framingham-REGICOR (10.8%). The real incidence of coronary events was 14.7% (p <
      0.001). Statistically significant differences between patients with or without
      coronary events were only observed in the Framingham-REGICOR equation (13.3% vs
      10.3%; p = 0.046). Framingham-Anderson and Framingham-Wilson functions charts
      more than doubled the risk of coronary disease in men (p < 0.001). The agreement
      degree between the 3 functions was acceptable except for the calculation of
      coronary risk in men between Framingham-REGICOR and Framingham-Wilson equations
      (kappa index = 0.3). Framingham-Anderson and Framingham-Wilson functions charts
      showed similar profiles for the patients with high coronary risk. Sensitivity was
      superior in Framingham-Anderson and Framingham-Wilson functions (67.8%) and
      specificity was optimal in Framingham-REGICOR equation (51.2%). The positives
      predictive values were low and the negatives predictive values were high.
      CONCLUSIONS: The equations of Framingham-Wilson and Framingham-Anderson
      overestimate the coronary risk in diabetics, whereas the Framingham-REGICOR
      functions underestimates it. The utility of these 3 methods is reduced in the
      diabetic population.

PMID- 16624227
TI  - [Maintenance electroconvulsive therapy in elderly psychotic unipolar depression].
AB  - BACKGROUND AND OBJECTIVE: This study was designed to assess the safety and
      efficacy of continuation/maintenance electroconvulsive therapy (ECT) in elderly
      psychotic major depressed patients after ECT remission. PATIENTS AND METHOD:
      Using a longitudinal randomized single-blind design, we compared the two-year
      outcome of two subgroups of psychotic unipolar depressed elderly patients who
      were ECT remitters: one treated with a maintenance nortriptyline regimen (n = 13)
      and one treated with combined maintenance ECT plus nortriptyline (n = 6).
      RESULTS: During 2 years of maintenance treatment in elderly psychotic unipolar
      depressed ECT remitters, relapse/recurrence rates were significantly higher in
      the nortriptyline subgroup than in the combined ECT plus nortriptyline subgroup.
      The tolerability of both treatments was similar. CONCLUSIONS: This study supports
      the use of combined maintenance ECT and antidepressant treatment in elderly
      psychotic unipolar depressed patients who are ECT remitters.

PMID- 16624228
TI  - [Depression and electroconvulsive therapy in elderly subjects].

PMID- 16624229
TI  - [Risk score for diabetic patients. Is really necessary?].

PMID- 16624230
TI  - [Towards evidence-based medicine perversion?].

PMID- 16624231
TI  - [Attention deficit-hyperactivity disorder and sleep disorders].
AB  - The attention deficit hyperactivity disorder (ADHD) is an heterogeneous, complex
      and common childhood disorder that causes significant impairment of child's
      functioning. This paper reviews the epidemiology, etiology, diagnosis,
      comorbidity, course and treatment of ADHD. Special attention is paid to sleep
      problems both because these 2 conditions frequently co-exist and because there is
      substantial evidence that ADHD psychopathology and sleep-wake regulation share
      common neurobiologic mechanisms. Moreover, there could be an overlap between
      symptoms of ADHD and certain sleep problems such as obstructive sleep apnea
      syndrome, restless leg syndrome and periodic limb movements of sleep. Children
      undergoing evaluation for ADHD should be systematically assessed for sleep
      disturbances because treatment of sleep disorders is often associated with
      improved symptomatology and decreased need for stimulants.

PMID- 16624232
TI  - [Diagnosis and antibiotic treatment of external otitis].

PMID- 16624233
TI  - [Coronary artery disease in young people and metabolic syndrome].

PMID- 16624234
TI  - [Cell phone devices and fibromyalgia].

PMID- 16624235
TI  - [Dermatomyositis, lipodystrophy and insulin resistance].

PMID- 16624236
TI  - [Considerations regarding the curricular value of scientific publications].

PMID- 16624237
TI  - [Transferrin saturation in the diagnostic algorithm of genetic hemochromatosis].

PMID- 16624238
TI  - [Extraintestinal manifestations in inflammatory bowel disease: differences
      between Crohn's disease and ulcerative colitis].

PMID- 16624239
TI  - [Immune restoration syndrome secondary to hepatitis C virus infection in an HIV
      infected pediatric patient].

PMID- 16624240
TI  - [Takayasu arteritis associated with ulcerative colitis].

PMID- 16624241
TI  - Strategies for comparing gene expression profiles from different microarray
      platforms: application to a case-control experiment.
AB  - Meta-analysis of microarray data is increasingly important, considering both the
      availability of multiple platforms using disparate technologies and the
      accumulation in public repositories of data sets from different laboratories. We
      addressed the issue of comparing gene expression profiles from two microarray
      platforms by devising a standardized investigative strategy. We tested this
      procedure by studying MDA-MB-231 cells, which undergo apoptosis on treatment with
      resveratrol. Gene expression profiles were obtained using high-density, short
      oligonucleotide, single-color microarray platforms: GeneChip (Affymetrix) and
      CodeLink (Amersham). Interplatform analyses were carried out on 8414 common
      transcripts represented on both platforms, as identified by LocusLink ID,
      representing 70.8% and 88.6% of annotated GeneChip and CodeLink features,
      respectively. We identified 105 differentially expressed genes (DEGs) on CodeLink
      and 42 DEGs on GeneChip. Among them, only 9 DEGs were commonly identified by both
      platforms. Multiple analyses (BLAST alignment of probes with target sequences,
      gene ontology, literature mining, and quantitative real-time PCR) permitted us to
      investigate the factors contributing to the generation of platform-dependent
      results in single-color microarray experiments. An effective approach to cross
      platform comparison involves microarrays of similar technologies, samples
      prepared by identical methods, and a standardized battery of bioinformatic and
      statistical analyses.

PMID- 16624242
TI  - Real-time monitoring of DNA polymerase activity using molecular beacon.

PMID- 16624243
TI  - Enzymatic and chemical methods for the generation of pure hyaluronan
      oligosaccharides with both odd and even numbers of monosaccharide units.
AB  - Hyaluronan oligosaccharides display physiological activities not associated with
      the polymer and are widely used to characterize hyaluronan-binding proteins. They
      can also be used as biocompatible starting blocks for chemical derivatization.
      Here we present methods for generating milligram quantities of unusual odd- and
      even-numbered oligosaccharides, greatly increasing the diversity of reagents for
      use in such studies. These methods are based upon protocols from the 1960s, at
      which time it was very difficult to assess the stereochemical purity of the
      products. To address this, products were analyzed with modern high-field nuclear
      magnetic resonance spectroscopy. Alkaline beta-elimination conditions previously
      used to remove reducing-terminal N-acetylglucosamine residues in fact introduce a
      significant ( approximately 30%) level of stereoisomerism in the products by
      alkali-catalyzed keto-enol tautomerizations. Milder alkaline conditions were used
      to overcome this problem, reducing the contamination to <5%. The elimination by
      products from this reaction were isolated and characterized, allowing the
      mechanism of alkaline degradation of hyaluronan to be investigated for the first
      time. beta-Glucuronidase was used to remove nonreducing-terminal glucuronic acid
      residues from oligosaccharides. Odd-numbered oligosaccharides with terminal
      glucuronic acid residues isolated from hyaluronidase digests are shown to
      originate from acid-catalyzed acetal hydrolysis during boiling denaturation and
      also have significant levels of stereochemical impurities.

PMID- 16624244
TI  - A natural carrier effect and the generation of specific antibodies to
      biologically active peptides.
AB  - Production of specific antibodies to haptens, especially antipeptides, without
      interference by carrier protein, is desirable. The bradykinin-potentiating
      peptides (BPPs) are a family of pyroglutamyl proline-rich oligopeptides with
      strong antihypertensive properties. In this work, the production of antibodies to
      BPPs by use of an efficient immunization protocol in mice genetically modified
      for the high antibody responsiveness (H(III) line) is described. Although it was
      possible to induce antibody production by single-dose administration of free
      BPPs, higher antibody titers were obtained in mice preimmunized with carrier
      protein before administration of peptides conjugated to this carrier.
      Interestingly, both mouse groups had a higher titer of IgG(1) than IgG(2a)
      isotypes, regardless of prior immunization with the carrier protein. However, a
      lower titer of IgG(2a) was observed in unprimed mice. A single band of about
      27kDa corresponding to the BPP precursor protein was recognized by these
      antibodies in the cytosol of the Bothrops jararaca venom gland. This work
      proposes an efficient immunization protocol based on classic studies described
      for the hapten-carrier effect for generating specific antibodies against
      biologically active peptides.

PMID- 16624245
TI  - Allosteric modulation of the human P-glycoprotein involves conformational changes
      mimicking catalytic transition intermediates.
AB  - The drug transport function of human P-glycoprotein (Pgp, ABCB1) can be inhibited
      by a number of pharmacological agents collectively referred to as modulators or
      reversing agents. In this study, we demonstrate that certain thioxanthene-based
      Pgp modulators with an allosteric mode of action induce a distinct conformational
      change in the cytosolic domain of Pgp, which alters susceptibility to proteolytic
      digestion. Both cis and trans-isomers of the Pgp modulator flupentixol confer
      considerable protection of an 80 kDa Pgp fragment against trypsin digestion, that
      is recognized by a polyclonal antibody specific for the NH(2)-terminal half to
      Pgp. The protection by flupentixol is abolished in the Pgp F983A mutant that is
      impaired in modulation by flupentixols, indicating involvement of the allosteric
      site in generating the conformational change. A similar protection to an 80 kDa
      fragment is conferred by ATP, its nonhydrolyzable analog ATPgammaS, and by
      trapping of ADP-vanadate at the catalytic domain, but not by transport substrate
      vinblastine or by the competitive modulator cyclosporin A, suggesting different
      outcomes from modulator interaction at the allosteric site and at the substrate
      site. In summary, we demonstrate that allosteric interaction of flupentixols with
      Pgp generates conformational changes that mimic catalytic transition
      intermediates induced by nucleotide binding and hydrolysis, which may play a
      crucial role in allosteric inhibition of Pgp-mediated drug transport.

PMID- 16624246
TI  - Inhibition of indoleamine 2,3 dioxygenase activity by H2O2.
AB  - Indoleamine 2,3-dioxygenase is the first and rate limiting enzyme of the
      kynurenine pathway of tryptophan metabolism, has potent effects on cell
      proliferation and mediates antimicrobial, antitumorogenic, and immunosuppressive
      effects. As a potent cytotoxic effector, the mechanisms of indoleamine 2,3
      dioxygenase inhibition deserve greater attention. The work presented here
      represents the first systematic study exploring the mechanisms by which low
      levels of hydrogen peroxide (10-100 microM) inhibit indoleamine 2,3-dioxygenase
      in vitro. Following brief peroxide exposure both enzyme inhibition and structural
      changes were observed. Loss of catalysis was accompanied by oxidation of several
      cysteine residues to sulfinic and sulfonic acids, observed by electrospray and
      MALDI mass spectrometry. Enzyme activity could in part be preserved in the
      presence of sulfhydryl containing compounds, particularly DTT and methionine.
      However, these structural alterations did not prevent substrate (l-tryptophan)
      binding. Some enzyme activity could be recovered in the presence of thioredoxin,
      indicating that the inhibitory effect of H(2)O(2) is at least partially
      reversible in vitro. We present evidence that cysteine oxidation represents one
      mechanism of indoleamine 2,3-dioxygenase inhibition.

PMID- 16624247
TI  - S-(2-Succinyl)cysteine: a novel chemical modification of tissue proteins by a
      Krebs cycle intermediate.
AB  - S-(2-Succinyl)cysteine (2SC) has been identified as a chemical modification in
      plasma proteins, in the non-mercaptalbumin fraction of human plasma albumin, in
      human skin collagen, and in rat skeletal muscle proteins and urine. 2SC increases
      in human skin collagen with age and is increased in muscle protein of diabetic
      vs. control rats. The concentration of 2SC in skin collagen and muscle protein
      correlated strongly with that of the advanced glycation/lipoxidation end-product
      (AGE/ALE), N(epsilon)-(carboxymethyl)lysine (CML). 2SC is formed by a Michael
      addition reaction of cysteine sulfhydryl groups with fumarate at physiological
      pH. Fumarate, but not succinate, inactivates the sulfhydryl enzyme,
      glyceraldehyde-3-phosphate dehydrogenase in vitro, in concert with formation of
      2SC. 2SC is the first example of spontaneous chemical modification of protein by
      a metabolic intermediate in the Krebs cycle. These observations identify fumarate
      as an endogenous electrophile and suggest a role for fumarate in regulation of
      metabolism.

PMID- 16624248
TI  - Mitochondrial DNA and ageing.
AB  - The accumulation of mitochondrial DNA mutations has been proposed as a potential
      mechanism in the physiological processes of ageing and age-related disease.
      Although mitochondria have long been anticipated as a perpetrator of ageing,
      there was little experimental evidence to link these changes directly with the
      cellular pathology of ageing. Recently, considerable progress in understanding
      basic mitochondrial genetics and in identifying acquired mtDNA mutations in
      ageing has been made. Furthermore, the creation of mtDNA-mutator mice has
      provided the first direct evidence that accelerating the mtDNA mutation rate can
      result in premature ageing, consistent with the view that loss of mitochondrial
      function is a major causal factor in ageing. This review will, therefore, focus
      on recent developments in ageing research related to the role played by mtDNA.

PMID- 16624250
TI  - Protons @ interfaces: implications for biological energy conversion.
AB  - The review focuses on the anisotropy of proton transfer at the surface of
      biological membranes. We consider (i) the data from "pulsed" experiments, where
      light-triggered enzymes capture or eject protons at the membrane surface, (ii)
      the electrostatic properties of water at charged interfaces, and (iii) the
      specific structural attributes of proton-translocating enzymes. The pulsed
      experiments revealed that proton exchange between the membrane surface and the
      bulk aqueous phase takes as much as about 1 ms, but could be accelerated by added
      mobile pH-buffers. Since the accelerating capacity of the latter decreased with
      the increase in their electric charge, it was concluded that the membrane surface
      is separated from the bulk aqueous phase by a barrier of electrostatic nature.
      The barrier could arise owing to the water polarization at the negatively charged
      membrane surface. The barrier height depends linearly on the charge of
      penetrating ions; for protons, it has been estimated as about 0.12 eV. While the
      proton exchange between the surface and the bulk aqueous phase is retarded by the
      interfacial barrier, the proton diffusion along the membrane, between neighboring
      enzymes, takes only microseconds. The proton spreading over the membrane is
      facilitated by the hydrogen-bonded networks at the surface. The membrane-buried
      layers of these networks can eventually serve as a storage/buffer for protons
      (proton sponges). As the proton equilibration between the surface and the bulk
      aqueous phase is slower than the lateral proton diffusion between the "sources"
      and "sinks", the proton activity at the membrane surface, as sensed by the energy
      transducing enzymes at steady state, might deviate from that measured in the
      adjoining water phase. This trait should increase the driving force for ATP
      synthesis, especially in the case of alkaliphilic bacteria.

PMID- 16624249
TI  - Mitochondrial metabolism and aging in the filamentous fungus Podospora anserina.
AB  - The filamentous fungus Podospora anserina has a limited lifespan. In this
      organism, aging is systematically associated to mitochondrial DNA instability. We
      recently provided evidence that the respiratory function is a key determinant of
      its lifespan. Loss of function of the cytochrome pathway leads to the
      compensatory induction of an alternative oxidase, to a decreased production of
      reactive oxygen species and to a striking increase in lifespan. These changes are
      associated to the stabilization of the mitochondrial DNA. Here we review and
      discuss the links between these different parameters and their implication in the
      control of lifespan. Since we demonstrated the central role of mitochondrial
      metabolism in aging, the same relationship has been evidenced in several model
      systems from yeast to mice, confirming the usefulness of simple organisms as P.
      anserina for studying lifespan regulation.

PMID- 16624251
TI  - A hybrid of the transhydrogenases from Rhodospirillum rubrum and Mycobacterium
      tuberculosis catalyses rapid hydride transfer but not the complete, proton
      translocating reaction.
AB  - All transhydrogenases appear to have three components: dI, which binds NAD(H),
      and dIII, which binds NADP(H), protrude from the membrane, and dII spans the
      membrane. However, the polypeptide composition of the enzymes varies amongst
      species. The transhydrogenases of Mycobacterium tuberculosis and of
      Rhodospirillum rubrum have three polypeptides. Sequence analysis indicates that
      an ancestral three-polypeptide enzyme evolved into transhydrogenases with either
      two polypeptides (such as the Escherichia coli enzyme) or one polypeptide (such
      as the mitochondrial enzyme). The fusion steps in each case probably led to the
      development of an additional transmembrane helix. A hybrid transhydrogenase was
      constructed from the dI component of the M. tuberculosis enzyme and the dII and
      dIII components of the R. rubrum enzyme. The hybrid catalyses cyclic
      transhydrogenation but not the proton-translocating, reverse reaction. This shows
      that nucleotide-binding/release at the NAD(H) site, and hydride transfer, are
      fully functional but that events associated with NADP(H) binding/release are
      compromised. It is concluded that sequence mismatch in the hybrid prevents a
      conformational change between dI and dIII which is essential for the step
      accompanying proton translocation.

PMID- 16624252
TI  - Mitochondrial metabolic states and membrane potential modulate mtNOS activity.
AB  - The mitochondrial metabolic state regulates the rate of NO release from coupled
      mitochondria: NO release by heart, liver and kidney mitochondria was about 40-45%
      lower in state 3 (1.2, 0.7 and 0.4 nmol/min mg protein) than in state 4 (2.2, 1.3
      and 0.7 nmol/min mg protein). The activity of mtNOS, responsible for NO release,
      appears driven by the membrane potential component and not by intramitochondrial
      pH of the proton motive force. The intramitochondrial concentrations of the NOS
      substrates, L-arginine (about 310 microM) and NADPH (1.04-1.78 mM) are 60-1000
      times higher than their KM values. Moreover, the changes in their concentrations
      in the state 4-state 3 transition are not enough to explain the changes in NO
      release. Nitric oxide release was exponentially dependent on membrane potential
      as reported for mitochondrial H2O2 production [S.S. Korshunov, V.P. Skulachev,
      A.A. Satarkov, High protonic potential actuates a mechanism of production of
      reactive oxygen species in mitochondria. FEBS Lett. 416 (1997) 15-18.]. Agents
      that decrease or abolish membrane potential minimize NO release while the
      addition of oligomycin that produces mitochondrial hyperpolarization generates
      the maximal NO release. The regulation of mtNOS activity, an apparently voltage
      dependent enzyme, by membrane potential is marked at the physiological range of
      membrane potentials.

PMID- 16624253
TI  - F508del CFTR with two altered RXR motifs escapes from ER quality control but its
      channel activity is thermally sensitive.
AB  - Most cystic fibrosis (CF) patients carry the F508del mutation in the CFTR
      chloride channel protein resulting in its misassembly, retention in the
      endoplasmic reticulum (ER), and proteasomal degradation. Therefore,
      characterization of the retention and attempts to rescue the mutant CFTR are a
      major focus of CF research. Earlier, we had shown that four arginine-framed
      tripeptide (AFT) signals in CFTR participate in the quality control. Now we have
      mutated these four AFTs in all possible combinations and found that simultaneous
      inactivation of two of them (R29K and R555K) is necessary and sufficient to
      overcome F508del CFTR retention. Immunofluorescence staining of BHK cells
      expressing this variant indicates that it matures and is routed to the plasma
      membrane. Acquisition of at least some wild-type structure was detected in the
      pattern of proteolytic digestion fragments. Functional activity at the cell
      surface was evident in chloride efflux assays. However, single channel activity
      of the rescued mutant measured in planar lipid bilayers diminished as temperature
      was increased from 30 to 37 degrees C. These findings support the idea that
      absence of Phe 508 causes not only a kinetic folding defect but also steady-state
      structural instability. Therefore effective molecular therapies developed to
      alleviate disease caused by F508del and probably other misprocessing mutants will
      require overcoming both their kinetic and steady-state impacts.

PMID- 16624254
TI  - Redox-regulated ion channel activity of a cysteine-containing gramicidin A
      analogue.
AB  - According to recent data, gramicidin A analogues having positively charged amino
      acid sequences at the C-termini exhibit two types of channel activity in lipid
      membranes: classical cation-selective channels and large unselective pores. The
      induction of unselective pores was shown here to strongly depend on the redox
      state of the membrane-bathing solution, if the gramicidin analogue contained a
      cysteine residue in the sequence GSGPKKKRKVC attached to the C-terminus. In
      particular, the addition of H2O2 led to an increase in the transmembrane current
      and the loss of cationic selectivity on planar bilayer lipid membranes and an
      increase in the carboxyfluorescein leakage of liposomes. The effect was observed
      at high concentration of the peptide while was absent at the single-channel
      level. It was concluded that oxidation led to possible formation of dimers of the
      peptide, which promoted the formation of large unselective pores.

PMID- 16624255
TI  - Regulation of aquaporin-2 trafficking and its binding protein complex.
AB  - Trafficking of water channel aquaporin-2 (AQP2) to the apical membrane is
      critical to water reabsorption in renal collecting ducts and its regulation
      maintains body water homeostasis. However, exact molecular mechanisms which
      recruit AQP2 are unknown. Recent studies highlighted a key role for spatial and
      temporal regulation of actin dynamics in AQP2 trafficking. We have recently
      identified AQP2-binding proteins which directly regulate this trafficking: SPA-1,
      a GTPase-activating protein (GAP) for Rap1, and cytoskeletal protein actin. In
      addition, a multiprotein "force generator" complex which directly binds to AQP2
      has been discovered. This review summarizes recent advances related to the
      mechanism for AQP2 trafficking.

PMID- 16624256
TI  - Metabolism of oxidants by blood from different mouse strains.
AB  - Haemoglobins bearing reactive sulfhydryl groups have been shown to be able to
      interplay with glutathione in some detoxification processes. Blood from different
      mouse strains commonly used as experimental animal models, i.e., C57, DBA and
      ICR, was treated with oxidants with the aim of evaluating: (i) the involvement of
      protein SH groups in oxido-reductive reactions that are commonly carried out by
      glutathione and (ii) the impact of this phenomenon on blood-mediated metabolism
      of thiol reactants. All the main forms of glutathione (reduced, disulfide, and
      mixed disulfide with haemoglobin) were measured after oxidant treatment.
      Significant differences were found among the studied strains: DBA mice formed
      preferably mixed disulfides instead of glutathione disulfide, whereas the
      opposite behaviour was shown by C57 mice. Unexpectedly, the ICR strain resulted
      to be composed of three different subgroups (ICRa, ICRb, and ICRc), with the ICRa
      behaving similarly to the DBA strain, ICRc to the C57 strain, and ICRc showing an
      intermediate behaviour. These results are due to the different number of
      haemoglobin SH groups in the studied mouse strains. In particular, additional
      fast-reacting SH groups were found in haemoglobin from DBA, ICRa, and ICRb mice,
      but not in the C57 and ICRc strain. These differences were also reflected in the
      susceptibility of haemoglobin to dimerize and in its ability to react with S
      nitrosocysteine. Because of the widely different reactivity of haemoglobin
      cysteinyl residues, the mouse strains examined are an interesting but complicated
      model in which to study the pharmacological and toxicological action of some
      drugs.

PMID- 16624257
TI  - Post-stress facilitation of serotonergic, but not noradrenergic,
      neurotransmission in the dorsal hippocampus prevents learned helplessness
      development in rats.
AB  - Recent pieces of evidence suggest that the dorsal hippocampus may mediate
      adaptation to severe and inescapable stress, possibly by the facilitation of
      serotonergic and/or noradrenergic neurotransmission. Chronic social stress and
      high corticosteroid levels would impair this coping mechanism, predisposing
      animals to learned helplessness. To test the hypothesis that increasing serotonin
      or noradrenaline levels in the dorsal hippocampus would attenuate the development
      of learned helplessness (LH), rats received inescapable foot shock (IS) and were
      tested in a shuttle box 24 h latter. Prestressed animals showed impairment of
      escape responses. This effect was prevented by bilateral intrahippocampal
      injections of zimelidine (100 nmol/0.5 microl), a serotonin reuptake blocker,
      immediately after IS. This effect was not observed when zimelidine was
      administered before or 2 h after IS. Bilateral intrahippocampal injections of
      desipramine (3 or 30 nmol/0.5 microl), a noradrenaline reuptake blocker, before
      IS or immediately after it did not prevent LH development. Desipramine (30 nmol)
      enhanced LH development when injected before IS. These data suggest that
      poststress facilitation of hippocampal serotonergic, but not noradrenergic,
      neurotransmission in the dorsal hippocampus facilitates adaptation to severe
      inescapable stress. Antidepressant effects of noradrenaline-selective drugs seem
      to depend on other structures than the dorsal hippocampus.

PMID- 16624258
TI  - Procolipase gene expression in the rat brain: source of endogenous enterostatin
      production in the brain.
AB  - Enterostatin is a pentapeptide released from its precursor protein procolipase,
      which is synthesized in the exocrine pancreas and gastric mucosa. As central
      injection of enterostatin has potent effects on feeding, we hypothesized that the
      procolipase may also be expressed in the brain. We confirmed the presence of
      preprocolipase gene expression in amygdala by reverse transcription-polymerase
      chain reaction and Northern blot analysis and of protein expression by Western
      blots. Immunohistochemical analysis using antibodies for procolipase and
      enterostatin identified their immunoreactivity (IR) in rat brain. Procolipase IR
      was present in the cytoplasm of paraventricular, amygdala, and the dorsal
      thalamus nucleus. Enterostatin IR was evident in the fibers of the dorsal
      thalamus and arcuate nucleus. In vivo injection of enterostatin antibody into rat
      amygdala increased food intake. These data suggest that procolipase and
      enterostatin are synthesized within specific regions of the brain that function
      in the regulation of food intake centrally.

PMID- 16624259
TI  - The effect of pre- and posttreatment with diazoxide on the early phase of chronic
      cerebral hypoperfusion in the rat.
AB  - Diazoxide has been identified as a mitochondrial, ATP-dependent K(+) channel
      opener, and a potentially neuroprotective compound under ischemic conditions. We
      set out to characterize the consequences of various treatment strategies with
      diazoxide in a rat model of chronic cerebral hypoperfusion. Cerebral
      hypoperfusion was induced by permanent, bilateral occlusion of the common carotid
      arteries (2VO, n = 36), sham-operated rats serving as controls (SHAM, n = 29).
      Diazoxide or its vehicle was administered i.p. daily (5 x 0.5 mg/kg/0.25 ml) or
      as a bolus injection (5 mg/kg/0.25 ml) before surgery or daily after surgery (5 x
      0.5 mg/kg/0.25 ml). Spatial learning performance was assessed 1 week after 2VO in
      the Morris maze. Hippocampal pyramidal cell loss was assessed on cresyl violet
      stained sections, while glial reactivity was labeled immunocytochemically. Daily
      or bolus pretreatment with diazoxide significantly improved 2VO-related learning
      impairment, whereas posttreatment was ineffective. The number of CA1 pyramidal
      neurons was reduced by 2VO, which was prevented by repeated or bolus pretreatment
      with diazoxide. Astrocyte proliferation and microglial activation were enhanced
      by posttreatment with diazoxide in the hippocampus CA1 area of 2VO animals as
      compared with SHAM. These data demonstrate that the neuroprotective effect
      exerted by diazoxide depends on the time of administration with respect to the
      onset of ischemia; pretreatment but not posttreatment with the compound has
      proved to be neuroprotective in chronic cerebral hypoperfusion. Thus,
      pretreatment with diazoxide offers therapeutical prospects for the treatment of
      cerebral ischemia.

PMID- 16624260
TI  - C-reactive protein in atherosclerosis: A causal factor?
AB  - Atherosclerosis is considered a to be multifactorial disease driven by
      inflammatory reactions. The process of inflammation also contributes to the
      pathogenesis of acute atherothrombotic events. C-reactive protein (CRP) is an
      acute phase protein and its concentration in serum reflects the inflammatory
      condition of the patient. Levels of CRP are consistently associated with
      cardiovascular disease (CVD) and predict myocardial infarctions and stroke. Since
      CRP is present in the atherosclerotic lesion, it may actively contribute to the
      progression and/or instability of the atherosclerotic plaque. The role of CRP in
      inflammation and its causality in atherosclerosis are the subject of many
      investigations but are not yet fully elucidated. This review focuses on recently
      identified mechanisms by which CRP may modulate and evolve the process of
      atherosclerosis. We discuss the function of CRP and review the most recent
      evidence for an independent role of CRP in the development of atherosclerosis.
      Many studies suggest such a role, but a number of the described effects may be
      the result of contamination of the CRP preparations.

PMID- 16624261
TI  - Papilloma protein E6 abrogates shear stress-dependent survival in human
      endothelial cells: evidence for specialized functions of paxillin.
AB  - BACKGROUND: To investigate how endothelial cells transduce intracellular signals
      in response to laminar shear stress (SS), we made use of the papilloma virus
      oncoprotein E6 which interacts with and induces degradation of numerous cellular
      proteins including p53 and members of the PDZ-domain family. E6 also recognizes
      paxillin (PXN), a fundamental component of focal adhesions, interfering with its
      association to focal adhesion kinase (FAK). METHODS AND RESULTS: Human umbilical
      vein endothelial cells, expressing E6 or its mutated variant DeltaE6(105-110)
      (DeltaE6) which does not inactivate p53, were cultured under static conditions or
      exposed to a laminar SS of 12 dyn/cm(2) for 16h. In response to SS, cells
      expressing E6 or DeltaE6 failed to synthesise nitric oxide and directionally
      remodel their cytoskeleton, as indicated by morphology and phalloidin staining of
      actin microfilaments. Under these conditions, PXN association with FAK, its
      localization to the plasma membrane, and its phosphorylation on tyrosine-31,
      which partially encompasses the PXN/FAK docking site, were severely compromised.
      These alterations were paralleled by the impairment of important SS-dependent
      endothelial functions, including nitric oxide production and survival upon serum
      deprivation. The direct targeting of PXN expression by RNA interference partially
      reproduced the E6 phenotype, impairing flow-dependent cell orientation and
      survival but not nitric oxide production. CONCLUSIONS: These results provide
      evidence that papilloma virus E6 protein interferes with the function of the SS
      mechanosensor and suggests a potential a role for PXN in this process.

PMID- 16624262
TI  - The RyR2 central domain peptide DPc10 lowers the threshold for spontaneous Ca2+
      release in permeabilized cardiomyocytes.
AB  - OBJECTIVE: In vitro experiments have shown that the ryanodine receptor-2 (RyR2)
      central domain peptide DPc10 (Gly(2460)-Pro(2495)) mimics channel dysfunction
      associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) by
      acting competitively to reduce stabilizing interactions between the N-terminal
      and central domains. In the present study, DPc10 was used as a tool to establish
      an adult cell model of the disease and to analyse the underlying mechanisms.
      METHODS: Rat ventricular myocytes were permeabilized with saponin and perfused
      with solutions approximating the intracellular milieu containing fluo-3.
      Sarcoplasmic reticulum (SR) Ca(2+) release was detected using confocal
      microscopy. DPc10 (10 or 50 microM) was compared with 0.2 mM caffeine, which is
      known to activate RyR2 and to facilitate Ca(2+)-induced Ca(2+) release (CICR).
      RESULTS: Introduction of DPc10 induced a transient increase in spark frequency
      and a sustained rise in resting [Ca(2+)]. Under conditions causing initial Ca(2+)
      overload of the SR, DPc10 reduced the frequency and amplitude of spontaneous,
      propagated Ca(2+) release (SPCR). Following equilibration with 10microM DPc10,
      the cytosolic [Ca(2+)] threshold for SPCR was markedly reduced and the proportion
      of spontaneously active cells increased. Caffeine induced a similar, transient
      increase in spark frequency and a reduction in the [Ca(2+)] threshold for SPCR.
      However, unlike DPc10, caffeine increased SPCR frequency and had no sustained
      effect on resting [Ca(2+)]. These results suggest that the net effect of DPc10
      (and CPVT mutations) on RyR2 function in situ is not only to increase the
      sensitivity to CICR as caffeine does, but also to potentiate Ca(2+) leakage from
      the SR. As SPCR can trigger delayed after-depolarisations, the decrease in
      [Ca(2+)] threshold may contribute to arrhythmias in CPVT patients during exercise
      or stress.

PMID- 16624264
TI  - Determination of 5-methyltetrahydrofolate in cerebrospinal fluid of paediatric
      patients: reference values for a paediatric population.
AB  - BACKGROUND: Cerebral folate deficiency (CFD) has been described as a neurological
      syndrome associated with low 5-methyltetrahydrofolate (5-MTHF) values in
      cerebrospinal fluid (CSF) with normal folate concentrations in plasma. Our aim
      was to analyse CSF 5-MTHF concentrations in a paediatric control population and
      in patients with various neurological disorders. METHODS: We studied plasma and
      CSF samples from 63 paediatric controls (age range: 2 days to 18 years, average:
      3.8 years) and from 165 patients (age range: 1 day to 22 years, average: 5.0
      years) with severe epileptic encephalopathies of unknown origin, movement
      disorders, Rett syndrome and mitochondrial diseases. CSF 5-methyltetrahydrofolate
      was analysed by reverse phase HPLC with fluorescence detection (excitation: 295
      nm and emission: 355 nm). RESULT: A negative correlation between 5-MTHF values
      and age of controls was observed (r=-0.468; p<0.0001) and reference values were
      therefore stratified into 3 age groups. Regarding patients, 122 out of 165 showed
      normal CSF 5-MTHF values while 43 showed decreased values ranging from profound
      to mild deficiencies. Increased CSF total protein values were associated with the
      presence of low 5-MTHF concentrations (chi(2)=7.796; p=0.005). CONCLUSIONS: The
      application of this method has been useful for the establishment of reference
      values and for diagnosis of CFD in paediatric patients. Furthermore, increased
      CSF total protein concentrations should be considered as a marker of a possible
      CFD.

PMID- 16624265
TI  - Enhanced lipid peroxidation in tourniquet-release mice.
AB  - BACKGROUND: The pathogenesis of ischemia-reperfusion involves generation of
      reactive oxygen and resulting lipid peroxidation. However, investigation that
      ischemia-reperfusion following tourniquet release enhances lipid peroxidation is
      insufficient. METHODS: Tourniquet was applied to a unilateral hind limb of mice
      for 3h followed by 5-, 15-, 30- and 60-min release. To examine superoxide
      production immunohistochemically in ischemia-reperfusion muscles, a primary
      antibody directed to 4-hydroxy-nonenal (HNE) was used. Furthermore, we analyzed
      7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol, 7alpha- and 7beta
      hydroxycholesterol, and 7-ketocholesterol by HPLC in the gastrocnemius muscles,
      kidneys, liver, heart and lungs of mice after 1-h reperfusion. RESULTS: Increased
      HNE immunoreactivitiy was observed in the tourniquet-applied side of
      gastrocnemius muscles of hind limb particularly after 5-min reperfusion. All the
      oxysterols were significantly higher in the gastrocnemius muscles of the
      tourniquet-applied side than of the contralateral muscles. Oxysterols were
      elevated in the kidneys and the liver. Together with the presence of high blood
      urea nitrogen, these data indicate that the kidney is vulnerable to ischemia
      reperfusion. CONCLUSIONS: The enhanced oxidative stress due to ischemia
      reperfusion appears to increase HNE in muscle and oxysterols by peroxidation not
      only in the gastrocnemius muscles but also in the kidneys and liver.

PMID- 16624266
TI  - Analysis of ligand binding by bioaffinity mass spectrometry.
AB  - BACKGROUND: Ligand binding is commonly analyzed using various immunoassays that
      are generally time-consuming and some may require secondary antibodies or gel
      electrophoresis which are also time-consuming and sometimes subjective. We
      introduced various examples for a more rapid approach using pre-activated surface
      chips which are analyzed by surface enhanced laser desorption/ionization-time of
      flight mass spectrometry (SELDI-TOF MS). Specific applications presented in this
      study include immobilization of antigen, antibody or oligo DNA on pre-activated
      chips with subsequent identification of the binding antibodies, antigens or DNA
      binding proteins to demonstrate the universal utility of this novel approach.
      METHODS: BSA-digoxin conjugate (BSA-Dig), anti-digoxin antibody, anti-urinary
      trypsin inhibitor (uTi) antibody, or a double stranded oligo nucleotide based on
      the nucleotide sequence between -91 and -10 of the human CYP 450 2E1 promoter
      were immobilized on the Ciphergen pre-activated surface chips. Anti-digoxin
      antibody, BSA-digoxin conjugate, uTi, and CYP450 2E1 promoter binding protein
      were captured on the chip and identified by SELDI-TOF MS. RESULTS: A protein with
      141kDa was identified from anti-digoxin serum using BSA-Dig chips. This binding
      was competitively inhibited by addition of digoxin. Using anti-digoxin antibody,
      a peak at approximately 66kDa was detected in the preparation of BSA-Dig. This
      peak was also inhibited by free digoxin, suggesting BSA-Dig is detected. uTi
      fragments with approximately 3kDa to approximately 30kDa in the standard and
      urine samples were captured on the chip by anti-uTi antibody. Finally, we
      identified a 95-kDa CYP 450 2E1 promoter binding protein in HeLa cells nuclear
      extracts. CONCLUSIONS: Bioaffinity SELDI-TOF MS is a powerful and versatile
      approach for analysis of ligands. It eliminates tracer-labeled secondary
      antibodies and allows for determination of molecular weights of binding proteins
      and their ligands directly. This approach may also be considered for the
      detection of enzymes, receptors, or any other specific ligands.

PMID- 16624267
TI  - State of the art in hair analysis for detection of drug and alcohol abuse.
AB  - Hair differs from other materials used for toxicological analysis because of its
      unique ability to serve as a long-term storage of foreign substances with respect
      to the temporal appearance in blood. Over the last 20 years, hair testing has
      gained increasing attention and recognition for the retrospective investigation
      of chronic drug abuse as well as intentional or unintentional poisoning. In this
      paper, we review the physiological basics of hair growth, mechanisms of substance
      incorporation, analytical methods, result interpretation and practical
      applications of hair analysis for drugs and other organic substances. Improved
      chromatographic-mass spectrometric techniques with increased selectivity and
      sensitivity and new methods of sample preparation have improved detection limits
      from the ng/mg range to below pg/mg. These technical advances have substantially
      enhanced the ability to detect numerous drugs and other poisons in hair. For
      example, it was possible to detect previous administration of a single very low
      dose in drug-facilitated crimes. In addition to its potential application in
      large scale workplace drug testing and driving ability examination, hair analysis
      is also used for detection of gestational drug exposure, cases of criminal
      liability of drug addicts, diagnosis of chronic intoxication and in postmortem
      toxicology. Hair has only limited relevance in therapy compliance control. Fatty
      acid ethyl esters and ethyl glucuronide in hair have proven to be suitable
      markers for alcohol abuse. Hair analysis for drugs is, however, not a simple
      routine procedure and needs substantial guidelines throughout the testing
      process, i.e., from sample collection to results interpretation.

PMID- 16624268
TI  - Leptin levels and body composition in children and adolescents with type 1
      diabetes.
AB  - The purpose of this study was to determine the relationship between serum leptin
      levels and body composition and to evaluate the variables related to disease in
      children and adolescents with type 1 diabetes. We studied 49 diabetic patients
      aged 6-16 years (age: 11.2+/-2.9 years, M/F: 26/23), and 37 healthy controls.
      Body composition was determined by dual-energy X-ray absorptiometry. Serum
      leptin, glycated hemoglobin (HbA1c), free thyroxin, thyrotropin, testosterone and
      estradiol levels were measured in patients and controls. We did not observe
      significant difference in serum leptin levels between patients and controls.
      Girls had significantly higher serum leptin levels than boys in both patient and
      control groups. Serum leptin levels did not correlate significantly with HbA1c,
      disease duration or daily insulin dose but, correlated positively with body mass
      index (BMI) and fat mass (FM) in patients as in controls. Body composition in
      diabetic girls and boys was similar with respective controls. When analyzed by
      pubertal stage, BMI, lean body mass (LBM), FM, and total bone mineral density
      (BMD) were significantly higher in pubertal girls with type 1 diabetes compared
      to prepubertal ones. In pubertal boys with type 1 diabetes, LBM and FM were
      significantly higher than prepubertal ones. The results of the present study
      showed that neither serum leptin levels nor body composition was significantly
      altered in children and adolescents with type 1 diabetes managed with intensive
      insulin therapy.

PMID- 16624269
TI  - Sialic acid: a novel marker of cardiovascular disease?
AB  - The global burden posed by cardiovascular disease (CVD), due to a rising
      incidence of known risk factors, underlines an urgent need to identify other
      potential risk factors. Sialic acid (SA), an abundant terminal monosaccharide of
      glycoconjugates, is a possible risk factor for CVD. Although large-scale
      epidemiological surveys have shown that serum total sialic acid (TSA) is
      positively associated with mortality from coronary artery disease (CAD) and
      stroke, studies investigating the correlation between serum TSA and the severity
      of atherosclerosis are conflicting. Clinical and epidemiological studies indicate
      that serum TSA is a marker of a sustained inflammatory response in CVD, rather
      than causal in nature. Data also indicates ethnic variation in baseline TSA. This
      article reviews current methods for determining serum TSA and evidence supporting
      serum TSA as a risk factor for CVD. Potential mechanisms for this role are
      examined. The use of serum TSA as a marker of atherosclerotic disease is
      evaluated.

PMID- 16624270
TI  - High-throughput genotyping with infrared fluorescence allele specific
      hybridization (iFLASH): a simple, reliable and low-cost alternative.
AB  - OBJECTIVES: To develop and validate a novel genotyping approach, named infrared
      Fluorescence Allele Specific Hybridization (iFLASH), which combines the
      principles of allele specific oligonucleotide (ASO) hybridization with the
      advanced possibilities of infrared imaging. DESIGN AND METHODS: As an example, we
      genotyped the 55L > M and the 192Q > R common genetic variants of the paraoxonase
      1 gene in 92 DNA samples using the iFLASH technique, and validated the outcomes
      with the restriction fragment length polymorphism (RFLP) and TAQman genotyping
      assays. RESULTS: There was a 100 percent agreement in genotype outcome among the
      three methods. CONCLUSIONS: Although we found complete unity in genotype outcome,
      the iFLASH assay has essential advantages over the RFLP and TAQman genotyping
      assays. First, the iFLASH technique is capable of handling up to 1536 samples per
      assay, which makes it a suitable technique for high-throughput genotyping.
      Secondly, because the costs per assay are lower, high-throughput genotyping with
      iFLASH is affordable.

PMID- 16624271
TI  - An evaluation of cytosolic erythrocyte carbonic anhydrase and catalase in
      carcinoma patients: an elevation of carbonic anhydrase activity.
AB  - OBJECTIVES: The antioxidant enzyme catalase and the CO2/HCO3- exchange enzyme
      carbonic anhydrase are both present in significant amounts in the cytosol of
      erythrocytes. The aim of the present study was to investigate whether these
      erythrocyte enzyme activities are altered in patients who have carcinoma. DESIGN
      AND METHODS: Cytosolic erythrocyte enzyme activities were measured in 108 cancer
      patients presenting with carcinoma at one of variable sites, prior to clinical
      treatment. These were compared with an age- and sex-matched control group of 31
      healthy volunteers. RESULTS: Mean (+/-SD) catalase activities did not differ
      significantly, i.e. 0.0035 (+/-0.0015) EU/ml in carcinoma patients vs. 0.0031 (+/
      0.00075) EU/ml in controls. However, mean carbonic anhydrase activities of 204
      (+/-91) EU/ml in the carcinoma patients were significantly higher than the 158
      (+/-35) EU/ml in controls (P value of 0.0065). CONCLUSION: Cytosolic erythrocyte
      carbonic anhydrase levels may warrant further investigation as a potential
      peripheral marker in cancer.

PMID- 16624272
TI  - Gap analysis of pediatric reference intervals for risk biomarkers of
      cardiovascular disease and the metabolic syndrome.
AB  - The childhood obesity epidemic has begun to compromise the health of the
      pediatric population by promoting premature development of atherosclerosis and
      the metabolic syndrome (MS), both of which significantly increase the risk of
      cardiovascular disease (CVD) early in life. As a result, recently, there has been
      increased recognition of the need to assess and closely monitor children and
      adolescents for risk factors of CVD and components of the MS. Serum/Plasma
      biomarkers including total cholesterol, triglycerides, HDL-C, LDL-C, insulin and
      C-peptide have been used for this purpose for many years. Recently, emerging
      biomarkers such as apolipoprotein AI, apolipoprotein B, leptin, adiponectin, free
      fatty acids, and ghrelin have been proposed as tools that provide valuable
      complementary information to that obtained from traditional biomarkers, if not
      more powerful predictions of risk. In order for biomarkers to be clinically
      useful in accurately diagnosing and treating disorders, age-specific reference
      intervals that account for differences in gender, pubertal stage, and ethnic
      origin are a necessity. Unfortunately, to date, many critical gaps exist in the
      reference interval database of most of the biomarkers that have been identified.
      This review contains a comprehensive gap analysis of the reference intervals for
      emerging and traditional risk biomarkers of CVD and the MS and discusses the
      clinical significance and analytical considerations of each biomarker.

PMID- 16624273
TI  - Oral phenylalanine loading test for the diagnosis of dominant guanosine
      triphosphate cyclohydrolase 1 deficiency.
AB  - OBJECTIVES: To evaluate the usefulness of Phe loading test in patients for the
      diagnosis of guanosine triphosphate cyclohydrolase 1 deficiency (GTPCH). DESIGN
      AND METHODS: We studied one family composed of 13 members harbouring the Q89X
      mutation in the GTPCH gene, a non-related pediatric patient with GTPCH deficiency
      and 8 pediatric controls. 100 mg/kg of L-phenylalanine was orally administered,
      and blood spot samples were taken at baselines 1, 2, 4 and 6 h post-load.
      RESULTS: Two out of 7 pediatric patients showed a phenylalanine/tyrosine ratio
      higher than the previously reported cut-off value of 5.25 at 4 h, while 6 of the
      7 adult patients showed a higher value. The only adult patient with a
      phenylalanine/tyrosine ratio below 5.25 at 4 h was asymptomatic. CONCLUSIONS: A
      cut-off value of 5.25 seems reliable for interpreting Phe loading test in adult
      patients with GTPCH deficiency, although a lower value should be established for
      pediatric patients.

PMID- 16624274
TI  - Possible contribution of serum activin A and IGF-1 in the development of
      hepatocellular carcinoma in Egyptian patients suffering from combined hepatitis C
      virus infection and hepatic schistosomiasis.
AB  - OBJECTIVES: The present study evaluated the role of activin A, insulin-like
      growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP
      3) in Egyptian patients suffering from combined hepatitis C virus (HCV) infection
      and hepatic schistosomiasis. DESIGN AND METHODS: Four groups were included in the
      present study. Group I: 30 healthy subjects were included as controls; Group II
      (HCV): 30 patients with chronic liver disease due to HCV infection without
      evidence of schistosomiasis; Group III (SHF + HCV): 30 patients with combined
      disease, chronic schistosomal hepatic fibrosis (SHF) and chronic hepatitis C
      infection; Group IV (HCC): 30 patients with hepatocellular carcinoma associated
      with chronic hepatitis C virus and schistosomal infection. RESULTS: Patients with
      HCV, HCV + SHF and those with HCC had a significantly higher serum activin A
      compared with the control group (P < 0.001). Serum activin A level (mean +/- SD)
      was 5.7 +/- 2.76, 10.59 +/- 3.59, 15.39 +/- 4.61 and 19.93 +/- 5.43 ng/mL in
      controls, HCV patients, HCV + SHF patients and HCC patients, respectively. Serum
      IGF-1 was significantly lower in HCV patients, HCV + SHF patients and HCC
      patients compared to the control group (P < 0.001). Serum IGF-1 was 121.7 +/-
      73.4, 76.7 +/- 23.5, 35.7 +/- 17.6 and 39.9 +/- 25.9 ng/mL in controls, HCV
      patients, HCV + SHF patients and HCC patients, respectively. Similarly, serum
      IGFBP-3 was significantly lower in HCV patients, HCV + SHF patients and HCC
      patients compared to the control group (P < 0.001). Furthermore, serum insulin
      like growth factor binding protein 3 (IGFBP-3) was significantly lower in
      patients with HCC compared to patients with HCV or those with HCV + SHF (P < 0.01
      and P = 0.024, respectively). The median (range) of serum IGFBP-3 was 4452 (352.2
      8965), 3457 (1114-6000), 2114 (867-5901) and 1202 (576-3994) ng/mL in controls,
      HCV patients, HCV + SHF patients and HCC patients, respectively. Serum activin A
      correlated positively with Child-Pugh scoring in patients with HCV, HCV + SHF and
      those with HCC. The correlation coefficient was significant, at 0.001, in total
      cases. CONCLUSIONS: We conclude that patients with HCV, HCV + SHF and those with
      HCC have a significantly higher serum activin A when compared with controls.
      Serum activin A level was significantly higher in patients with HCV + SHF
      compared to those with HCV alone (P < 0.01) with a significant positive
      correlation between the serum activin A level and Child-Pugh scoring in patients
      with HCV, HCV + SHF and those with HCC. Furthermore, serum IGF-1 and IGFBP-3
      levels were significantly reduced in patients with HCV, HCV + SHF and those with
      HCC compared to the control group. We suggest that this pattern (high activin A
      and low IGF-1 and its binding protein 3) may play a role in development of HCC in
      Egyptian patients suffering from combined hepatitis C virus infection and hepatic
      schistosomiasis.

PMID- 16624275
TI  - Explanatory models of illness: a study of within-culture variation.
AB  - The current studies explore causal models of heart attack and depression
      generated from American healers whom use distinct explanatory frameworks. Causal
      chains leading to two illnesses, heart attack and depression, were elicited from
      participant groups: registered nurses (RNs), energy healers, RN energy healers,
      and undergraduates. The domain-specificity hypothesis predicted that psycho
      social and physical causes would not interact in illness models. Across
      illnesses, RNs and undergraduates rarely cited interactions between mental and
      physical causes, consistent with the domain specificity hypothesis. In contrast,
      energy healers frequently mentioned interactions. Study 2 showed that these
      differences were not due to salience. These results suggest that domain
      specificity theory is supported for groups with extensive exposure to western
      medicine but does not explain energy models of illness. Implications for other
      cultural models of illness are discussed.

PMID- 16624276
TI  - The present environmental scenario of the Nador Lagoon (Morocco).
AB  - In this paper, we present a multivariate approach (waters, sediments, microfauna)
      concerning the environmental state of the Nador Lagoon (NE Morocco). The normal
      water quality parameters (salinity, pH, nutrients) of the dominant marine flows
      are altered by local fecal water effluents, urban discharges, sewages derived
      from a water treatment station, and residues originated in a slaughterhouse. The
      geochemical analyses carried out in surficial sediment samples show very high
      concentrations of all metals studied near an old iron mine and moderate contents
      between Nador and its treatment station. Ostracods are good bioindicators of
      these environmental impacts, with the presence of a highly brackish assemblage in
      the quieter, more confined areas or the appearance of opportunistic species under
      hypoxic conditions. In addition, these microcrustaceans are absent in polluted
      bottom sediments or areas with high hydrodynamic gradients, whereas they decrease
      in both density and diversity if the subaerial exposure increases.

PMID- 16624277
TI  - Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active
      constituent of Ligusticum chuanxiong, in rat isolated aorta.
AB  - Butylidenephthalide (BDPH) is one of the most potent vasorelaxants isolated from
      Ligusticum chuanxiong Hort. The objective of the current study is to investigate
      the underlying vasorelaxation mechanisms in rat aorta. In 9,11-dideoxy
      9alpha,11alpha-methanoepoxyprostaglandin F(2alpha) (U46619) precontracted
      preparations, endothelium removal, the nitric oxide (NO) synthase inhibitor
      Nomega-nitro-l-arginine methyl ester (l-NAME) and the soluble guanylate cyclase
      inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) partially inhibited
      the BDPH relaxation response to a similar extent. The cyclooxygenase inhibitor
      indomethacin, beta-adrenoceptor antagonist propranolol, adenylate cyclase
      inhibitors 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536) and 2',5'
      dideoxyadenosine, and K(+) channel blocker tetraethylammonium had no effect. BDPH
      produced full relaxation against contractions induced by KCl and U46619 in the
      presence of the l-type voltage-operated Ca(2+) channel (Ca(v) 1.2) blocker
      nifedipine. In a receptor-operated Ca(2+) channel protocol where contraction was
      mediated by Ca(2+) re-addition in the presence of U46619 and nifedipine, BDPH
      produced relaxation. In the absence of extracellular Ca(2+), BDPH inhibited
      contractions induced by phorbol-12,13-dibutyrate and U46619. Our results suggest
      that BDPH-mediated vasorelaxation comprises both endothelium-dependent (NO) and
      independent components. It is suggested that BDPH acting through an inhibitory
      mechanism downstream to l-type voltage-operated and prostanoid TP receptor
      operated Ca(2+) channels operating late in the contractile pathway.

PMID- 16624278
TI  - A novel experimental model of acute hypertriglyceridemia induced by schisandrin
      B.
AB  - Mice were intragastrically treated with single doses (0.05-0.8 g/kg) of
      schisandrin B (a dibenzocyclooctadiene derivative isolated from the fruit of
      Schisandra chinensis). Twenty-four hours after schisandrin B administration, the
      serum triglyceride level was increased by 10-235% in a dose-dependent manner.
      However, the serum low density lipoprotein cholesterol level was significantly
      decreased by 28% at a dose of 0.8 g/kg. When given once daily (0.01-0.2 g/kg) for
      4 days, schisandrin B also dose-dependently elevated the serum triglyceride level
      (17-134%). Kinetics parameters estimated by Scott's plot analysis of schisandrin
      B-induced changes in serum and hepatic triglyceride levels were determined: serum
      E(max) (maximal effect)=6 mmol/L (384% increase, P<0.001); K(D) (affinity)=0.59
      mmol/kg; pD(2) (an index of affinity)=6.62; liver-E(max)=21 micromol/g (68%
      increase, P<0.001); K(D)=0.37 mmol/kg; pD(2)=6.83. The efficacy of schisandrin B
      in increasing the triglyceride level was 5.6-fold higher in serum than in liver
      tissue. Fenofibrate (0.2g/kg) treatment, when in combination with schisandrin B
      (0.2g/kg), for 4 days significantly reduced the schisandrin B-induced increase in
      serum triglyceride level (by 81%, P<0.001). Hepatic triglyceride level was also
      decreased (by 100%, P<0.001) by co-treatment with fenofibrate. Our results
      suggest that schisandrin B treatment can be used to establish a mouse model of
      acute hypertrigylceridemia.

PMID- 16624279
TI  - Piperine inhibition of 1-methyl-4-phenylpyridinium-induced mitochondrial
      dysfunction and cell death in PC12 cells.
AB  - The effect of alkaloid piperine against the toxicity of 1-methyl-4
      phenylpyridinium (MPP(+)) in differentiated PC12 cells was assessed. Piperine
      treatment revealed a differential effect on the cytotoxicity of MPP(+) and had
      its maximum inhibitory effect at 1 microM. The addition of piperine (0.5-10
      microM) significantly reduced the MPP(+)-induced nuclear damage, mitochondrial
      membrane permeability changes, formation of reactive oxygen species and depletion
      of GSH. In contrast, piperine at 50-100 microM showed cytotoxicity and exhibited
      an additive effect against the MPP(+) toxicity. The results indicate that
      piperine had a differential effect on the cytotoxicity of MPP(+) depending on
      concentration. Piperine at low concentrations may reduce the MPP(+)-induced
      viability loss in PC12 cells by suppressing the changes in the mitochondrial
      membrane permeability, leading to the release of cytochrome c and subsequent
      activation of caspase-3. The effects may be ascribed to its inhibitory action on
      the formation of reactive oxygen species and depletion of GSH.

PMID- 16624280
TI  - Cinnamaldehyde reduces IL-1beta-induced cyclooxygenase-2 activity in rat cerebral
      microvascular endothelial cells.
AB  - Cinnamaldehyde is a principle compound isolated from Guizhi-Tang, which is a
      famous traditional Chinese medical formula used to treat influenza, common cold
      and other pyretic conditions. The aim of the present study was to investigate the
      effects of cinnamaldehyde on expression and activity of cyclooxygenase (COX) and
      prostaglandin E(2) (PGE(2)) in rat cerebral microvascular endothelial cells
      (RCMEC). RCMEC were cultured, and identified by immunohistochemistry for von
      Willebrand factor in cytoplasm of the cells. Then cells were incubated in M199
      medium containing interleukin (IL)-1beta in the presence or absence of
      cinnamaldehyde. After incubation, the medium was collected and the amount of
      PGE(2) was measured by enzyme-linked immunosorbent assay (ELISA). The cells were
      harvested, mRNA expression and activity of COX were analyzed by real-time reverse
      transcription-polymerase chain reaction (RT-PCR) with SYBR Green dye and ELISA
      respectively. Positive immunostaining for von Willebrand factor was present
      diffusely in the cytoplasm of >95% RCMEC. IL-1beta increased the mRNA expression
      and activity of COX-2, and production of PGE(2) in a dose- and time-dependent
      manner in RCMEC, while mRNA and activity of COX-1 were not significantly altered.
      Cinnamaldehyde significantly decreased IL-1beta-induced COX-2 activity and PGE(2)
      production in a dose-dependent manner, while it showed no inhibitory effect on IL
      1beta-induced COX-2 mRNA expression in cultured RCMEC. In conclusion,
      cinnamaldehyde reduces IL-1beta-induced COX-2 activity, but not IL-1beta-induced
      COX-2 mRNA expression, and consequently inhibits production of PGE(2) in cultured
      RCMEC.

PMID- 16624281
TI  - Co-distribution of the cannabinoid CB1 receptor and the 5-HT transporter in the
      rat amygdale.
AB  - Cannabis sometimes causes dysphoria rather than euphoria; however, evidence
      relating to the interaction between the cannabinoid and 5-hydroxtryptamine (5-HT)
      systems is limited, especially in areas of the brain such as the amygdale. Here
      we report that cannabinoid CB(1) receptors and 5-HT transporter proteins are co
      distributed in the amygdale, suggesting the possibility that activation of
      cannabinoid CB(1) receptors might cause a reduction in 5-HT release, similar to
      its effect on other neurotransmitters, thereby resulting in dysphoria.

PMID- 16624282
TI  - Inhibitory mechanisms of activated matrix metalloproteinase-9 on platelet
      activation.
AB  - The intracellular mechanisms underlying the signaling pathways of activated
      matrix metalloproteinase-9 (MMP-9) in platelets are not yet completely
      understood. Therefore, the aim of this study was to further examine the effects
      of activated MMP-9 in preventing platelet aggregation. In this study, activated
      MMP-9 time-dependently (3-60 min) inhibited platelet aggregation in washed human
      platelet suspensions stimulated by agonists. However, activated MMP-9 had no
      significant effect on the binding of FITC-triflavin to the platelet glycoprotein
      IIb/IIIa complex. Triflavin is a specific antagonist of the glycoprotein IIb/IIIa
      complex purified from snake venom. Moreover, activated MMP-9 (21 and 90 ng/ml)
      markedly decreased the fluorescence intensity of platelet membranes tagged with
      diphenylhexatriene. The thrombin-evoked increase in pHi was inhibited in the
      presence of activated MMP-9 (21 and 90 ng/ml). In addition, activated MMP-9 (21
      and 90 ng/ml) markedly reduced the electron spin resonance (ESR) signal intensity
      of hydroxyl radicals in collagen (1 mug/ml)-activated platelets. These results
      indicate that the antiplatelet activity of activated MMP-9 may involve the
      following pathways: (1) activated MMP-9 may initially induce conformational
      changes in platelet membranes and hydroxyl radical formation, leading to
      inhibition of platelet aggregation; and (2) activated MMP-9 also inhibits the
      Na(+)/H(+) exchanger, leading to reduced intracellular Ca(2+) mobilization, and
      ultimately to inhibition of platelet aggregation. This study further provides new
      insights concerning the effects of activated MMP-9 on platelet aggregation.

PMID- 16624283
TI  - Apoptosis induced by intracellular ceramide accumulation in MDA-MB-435 breast
      carcinoma cells is dependent on the generation of reactive oxygen species.
AB  - Strategies to promote intracellular ceramide accumulation in cancer cells may
      have therapeutic utility because ceramide is an important second messenger during
      apoptosis. Exposure to cell-permeable C(6) ceramide or tricyclodecan-9-yl
      xanthate (an inducer of de novo ceramide synthesis and an inhibitor of
      sphingomyelin synthase) caused MDA-MB-435 human breast carcinoma cells to die by
      apoptosis. Concomitant treatment with the ceramidase inhibitor D-erythro-2-(N
      myristoylamino)-1-phenyl-1-propanol (MAPP) or the glucosylceramide synthase
      inhibitor 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) potentiated
      the cytotoxic effect of C(6) ceramide, indicating that C(6) ceramide-mediated
      cytotoxicity was antagonized by the action of ceramidases and glucosylceramide
      synthase. Interestingly, treatment with PPMP alone, but not MAPP alone, also
      induced apoptosis in MDA-MB-435 cells, suggesting that conversion to
      glucosylceramide rather than catabolism by ceramidases prevented endogenous
      ceramide from reaching cytotoxic levels. C(6) ceramide-induced apoptosis in MDA
      MB-435 cells was associated with the generation of reactive oxygen species, and
      was inhibited by the antioxidants N-acetylcysteine and glutathione. Although
      mitochondrial membrane integrity was disrupted in C(6) ceramide-treated MDA-MB
      435 cells, apoptosis was not mediated by caspases because there was no protective
      effect by the pan-caspase inhibitor z-VAD-fmk. Collectively, these findings
      indicate that strategies to enhance intracellular ceramide accumulation in
      malignant cells might offer a novel approach to the treatment of breast cancer.

PMID- 16624285
TI  - The CB2 cannabinoid receptor signals apoptosis via ceramide-dependent activation
      of the mitochondrial intrinsic pathway.
AB  - Delta9-tetrahydrocannabinol and other cannabinoids exert pro-apoptotic actions in
      tumor cells via the CB2 cannabinoid receptor. However, the molecular mechanism
      involved in this effect has remained elusive. Here we used the human leukemia
      cell line Jurkat-that expresses CB2 as the unique CB receptor-to investigate this
      mechanism. Our results show that incubation with the selective CB2 antagonist
      SR144528 abrogated the pro-apoptotic effect of Delta9-tetrahydrocannabinol.
      Cannabinoid treatment led to a CB2 receptor-dependent stimulation of ceramide
      biosynthesis and inhibition of this pathway prevented Delta9-tetrahydrocannabinol
      induced mitochondrial hypopolarization and cytochrome c release, indicating that
      ceramide acts at a pre-mitochondrial level. Inhibition of ceramide synthesis de
      novo also prevented caspase activation and apoptosis. Caspase 8 activation-an
      event typically related with the extrinsic apoptotic pathway-was also evident in
      this model. However, activation of this protease was post-mitochondrial since (i)
      a pan-caspase inhibitor as well as a selective caspase 8 inhibitor were unable to
      prevent Delta9-tetrahydrocannabinol-induced loss of mitochondrial-membrane
      transmembrane potential, and (ii) cannabinoid-induced caspase 8 activation was
      not observed in Bcl-xL over-expressing cells. In summary, results presented here
      show that CB2 receptor activation signals apoptosis via a ceramide-dependent
      stimulation of the mitochondrial intrinsic pathway.

PMID- 16624284
TI  - Regulation of C/EBPbeta isoforms by MAPK pathways in HL60 cells induced to
      differentiate by 1,25-dihydroxyvitamin D3.
AB  - C/EBPbeta is known to be important for monocytic differentiation and macrophage
      function. Here, we found that expression of all three C/EBPbeta isoforms induced
      in HL60 cells by 1,25-dihydroxyvitamin D3 (1,25D) was upregulated in a sustained
      manner that correlates with the appearance of monocytic phenotype and with the G1
      phase cell cycle arrest. In 1,25D-resistant HL60-40AF cells, isoforms beta-1 and
      beta-3 were expressed at levels comparable to 1,25D-sensitive HL60-G cells, but
      isoform beta-2 was difficult to detect. Treatment of sensitive HL60 cells with
      1,25D resulted in predominantly nuclear localization of C/EBP isoforms beta-2 and
      beta-3, while a large proportion of C/EBPbeta-1 remained in the cytoplasm.
      Attenuation of the MEK-ERK MAPK pathway by the inhibitor PD98059 markedly reduced
      the expression, 1,25D-induced phosphorylation and nuclear localization of
      C/EBPbeta-2 and C/EBPbeta-3. Interestingly, only the lower molecular mass
      isoforms of C/EBPbeta phosphorylated on Thr235 were found in the nuclei, while
      C/EBPbeta-1 was constitutively phosphorylated and was detected principally in the
      cytoplasmic fraction. Although the role of C/EBPbeta isoforms in 1,25D-induced
      differentiation is complex, our results taken together strongly suggest that the
      phosphorylation of C/EBPbeta isoforms on Thr235 takes place mainly via the MEK
      ERK pathway and that C/EBPbeta-2 is the principal transcription factor in this
      cell system.

PMID- 16624286
TI  - Comparison of gene expression pattern in SP cell populations from four tissues to
      define common "stemness functions".
AB  - The goal of our study was to identify a subset of genes commonly expressed in
      Side Populations (SP), isolated by Hoechst staining followed by flow cytometry,
      from adult mouse bone marrow, male adult germinal cells, muscle primary culture,
      and mesenchymal cells. These SP cells have been proposed to be a "stem-like"
      population and are used here as a "model" that may reveal mechanisms which would
      be relevant for a better understanding of stem cell properties. Transcriptional
      profiles for SP and the more differentiated non-SP cells isolated from the four
      tissues were compared by hybridization on microarray using a common external
      reference. Among the 503 genes differentially expressed, which discriminate SP
      and non-SP cells in all the tissues, the genes upregulated in SP cells are
      implicated in the quiescent status of the cells, the maintenance of their
      pluripotency and the capacity to undergo asymmetric division. These genes may be
      responsible for the decision for self-renewal of these cells, whereas the
      repression of lineage-affiliated genes in SP cells could be responsible for their
      undifferentiated state. These genes, acting in concert, may be the key players
      that mediate the mechanisms that control stem cell functions, and our results
      suggest that we have identified common "stemness functions" of these "stem-like"
      cells.

PMID- 16624287
TI  - LUMA (LUminometric Methylation Assay)--a high throughput method to the analysis
      of genomic DNA methylation.
AB  - Changes in genomic DNA methylation are recognized as important events in normal
      and pathological cellular processes, contributing both to normal development and
      differentiation as well as cancer and other diseases. Here, we report a novel
      method to estimate genome-wide DNA methylation, referred to as LUminometric
      Methylation Assay (LUMA). The method is based on combined DNA cleavage by
      methylation-sensitive restriction enzymes and polymerase extension assay by
      Pyrosequencing. The method is quantitative, highly reproducible and easy to scale
      up. Since no primary modification of genomic DNA, such as bisulfite treatment, is
      needed, the total assay time is only 6 h. In addition, the assay requires only
      200-500 ng of genomic DNA and incorporates an internal control to eliminate the
      problem of varying amounts of starting DNA. The accuracy and linearity of LUMA
      were verified by in vitro methylated lambda DNA. In addition, DNA methylation
      levels were assessed by LUMA in DNA methyltransferase knock-out cell lines and
      after treatment with the DNA methyltransferase inhibitor (5-AzaCytidine). The
      LUMA assay may provide a useful method to analyze genome-wide DNA methylation for
      a variety of physiological and pathological conditions including etiologic,
      diagnostic and prognostic aspects of cancer.

PMID- 16624288
TI  - ROS up-regulation mediates Ras-induced changes of cell morphology and motility.
AB  - Expression of activated Ras causes an increase in intracellular content of
      reactive oxygen species (ROS). To determine the role of ROS up-regulation in
      mediation of Ras-induced morphological transformation and increased cell
      motility, we studied the effects of hydrogen peroxide and antioxidant NAC on
      morphology of REF52 rat fibroblasts and their ability to migrate into the wound
      in vitro. Treatment with low dosages of hydrogen peroxide leading to 1.5- to 2
      fold increase in intracellular ROS levels induced changes of cell shape, actin
      cytoskeleton organization, cell adhesions and migration resembling those in Ras
      transformed cells. On the other hand, treatment with NAC attenuating ROS up
      regulation in cells with conditional or constitutive expression of activated Ras
      led to partial reversion of morphological transformation and decreased cell
      motility. The effect of ROS on cell morphology and motility probably results from
      modulation of activity of Rac1, Rho, and cofilin proteins playing a key role in
      regulation of actin dynamics. The obtained data are consistent with the idea that
      ROS up-regulation mediates two key events in Ras-induced morphological
      transformation and cell motility: it is responsible for Rac1 activation and is
      necessary (though insufficient) for realization of Ras-induced cofilin
      dephosphorylation.

PMID- 16624289
TI  - Involvement of H- and N-Ras isoforms in transforming growth factor-beta1-induced
      proliferation and in collagen and fibronectin synthesis.
AB  - Transforming growth factor beta1 (TGF-beta1) has a relevant role in the origin
      and maintenance of glomerulosclerosis and tubule-interstitial fibrosis. TGF-beta
      and Ras signaling pathways are closely related: TGF-beta1 overcomes Ras mitogenic
      effects and Ras counteracts TGF-beta signaling. Tubule-interstitial fibrosis is
      associated to increases in Ras, Erk, and Akt activation in a renal fibrosis
      model. We study the role of N- and H-Ras isoforms, and the involvement of the Ras
      effectors Erk and Akt, in TGF-beta1-mediated extracellular matrix (ECM) synthesis
      and proliferation, using embrionary fibroblasts from double knockout (KO) mice
      for H- and N-Ras (H-ras(-/-)/N-ras(-/-)) isoforms and from heterozygote mice (H
      ras(+/-)/N-ras(+/-)). ECM synthesis is increased in basal conditions in H-ras(-/
      )/N-ras(-/-) fibroblasts, this increase being higher after stimulation with TGF
      beta1. TGF-beta1-induced fibroblast proliferation is smaller in H-ras(-/-)/N-ras(
      /-) than in H-ras(+/-)/N-ras(+/-) fibroblasts. Erk activation is decreased in H
      ras(-/-)/N-ras(-/-) fibroblasts; inhibition of Erk activation reduces fibroblast
      proliferation. Akt activation is higher in double KO fibroblasts than in
      heterozygotes; inhibition of Akt activation also inhibits ECM synthesis. We
      suggest that H- and N-Ras isoforms downregulate ECM synthesis, and mediate
      proliferation, in part through MEK/Erk activation. PI3K-Akt pathway activation
      may be involved in the increase in ECM synthesis observed in the absence of H-
      and N-Ras.

PMID- 16624290
TI  - Activity of a novel PDGF beta-receptor enhancer during the cell cycle and upon
      differentiation of neuroblastoma.
AB  - PDGF acts as an autocrine and paracrine factor in certain tumors through
      upregulation of the PDGF beta-receptor expression. In order to elucidate the
      control mechanism for the receptor expression, we have isolated an enhancer from
      two P1 clones that together contain a 102 kb NotI region covering the entire
      human PDGFRB gene. They were partially digested with TspI and cloned into the
      PDGFRB enhancer trap vector to make a library for identification of enhancers.
      The digested DNA containing enhancer was identified by expression of GFP when
      transfected in PDGF beta-receptor expressing cells. One of the enhancer clones
      was further examined by making several deletion mutants in a luciferase vector.
      This enhancer was most active in neuroblastoma cells, IMR32 and BE2, but less
      active in hemangioma and in smooth muscle cell lines. Chip assay revealed that
      SP1, AP2, and GATA2 bound the enhancer in BE2 cells. Their interaction occurred
      dependently of the cell cycle and synchronously with their binding to the
      promoter. Transfection of GATA2 alone or with Ets, which binds adjacent to GATA,
      resulted in differentiation of BE2 cells in parallel with increased PDGF beta
      receptor expression. Furthermore, over-expression of the PDGF beta-receptor in
      BE2 cells induced neurite extension.

PMID- 16624291
TI  - Blebbing of Dictyostelium cells in response to chemoattractant.
AB  - Stimulation of Dictyostelium cells with a high uniform concentration of the
      chemoattractant cyclic-AMP induces a series of morphological changes, including
      cell rounding and subsequent extension of pseudopodia in random directions. Here
      we report that cyclic-AMP also elicits blebs and analyse their mechanism of
      formation. The surface area and volume of cells remain constant during blebbing
      indicating that blebs form by the redistribution of cytoplasm and plasma membrane
      rather than the exocytosis of internal membrane coupled to a swelling of the
      cell. Blebbing occurs immediately after a rapid rise and fall in submembraneous F
      actin, but the blebs themselves contain little F-actin as they expand. A mutant
      with a partially inactivated Arp2/3 complex has a greatly reduced rise in F-actin
      content, yet shows a large increase in blebbing. This suggests that bleb
      formation is not enhanced by the preceding actin dynamics, but is actually
      inhibited by them. In contrast, cells that lack myosin-II completely fail to
      bleb. We conclude that bleb expansion is likely to be driven by hydrostatic
      pressure produced by cortical contraction involving myosin-II. As blebs are
      induced by chemoattractant, we speculate that hydrostatic pressure is one of the
      forces driving pseudopod extension during movement up a gradient of cyclic-AMP.

PMID- 16624292
TI  - Adaptation of rat soleus muscle spindles after 21 days of hindlimb unloading.
AB  - Spindle discharges are affected by muscle unloading, and changes in passive
      stiffness of the muscle-tendon unit may contribute to the changes in spindle
      solicitation. To test this hypothesis, we determined the spindle sensitivity from
      electroneurograms of the soleus nerve, and, concomitantly, we measured the
      incremental passive muscle tension. Both measurements were done from ramp and
      hold stretches imposed to the soleus muscle after the Achilles tendon was
      severed. The ratio between the spindle sensitivity and the passive stiffness gave
      a "spindle efficacy index" (SEI). The experiments were conducted on control rats
      (C, n = 12) and on rats that had undergone hindlimb unloading (HU, n = 12) for 21
      days. The muscle threshold lengths for electroneurogram to discharge (neurogram
      length, Ln) and for detecting passive tension (slack length, Ls) were determined,
      and, when these lengths differed, the stretches were imposed at these two initial
      lengths. The contralateral muscles were used to count muscle spindles and spindle
      fibers (ATPase staining) and to identify MyHC isoforms by immunostaining. Ln and
      Ls values were identical for the C muscles, while after HU, Ln was significantly
      shorter than Ls, which indicated that spindle afferents were more sensitive since
      they discharged before any passive tension was developed by the soleus muscle. At
      Ln, spindle sensitivity and passive stiffness did not differ for C and HU
      muscles. Consequently, when calculated at this relatively short initial muscle
      length, the SEI was maintained (or even slightly increased) after HU. This held
      under dynamic conditions (ramp phase of the stretch) and under static conditions
      (hold phase of the stretch). At Ls, the dynamic and static incremental stiffness
      values increased significantly after HU. Under dynamic conditions, the spindle
      sensitivity also increased after HU but to a less degree than incremental
      stiffness, which led to a significant decrease in SEI. Under static conditions,
      the spindle sensitivity presented a high increase, and, consequently, SEI was not
      modified. These functional changes were associated with structural adaptations:
      HU did not alter the total number of muscle spindles, but the number of spindles
      containing three nuclear chain fibers increased significantly. The main change in
      intrafusal MyHC content concerned the slow type I MyHC isoform. In conclusion,
      after a period of muscle unloading, the spindle discharges were maintained or
      even enhanced in several experimental conditions. This may be due to a better
      transmission of the external stretch to muscle spindles through stiffer elastic
      structures but also to own muscle spindle adaptations which reinforce the spindle
      sensitivity, notably under static conditions.

PMID- 16624293
TI  - Fluoxetine rescues deficient neurogenesis in hippocampus of the Ts65Dn mouse
      model for Down syndrome.
AB  - The Ts65Dn mouse, an adult model of Down syndrome displays behavioral deficits
      consistent with a dysfunctional hippocampus, similar to that seen with DS. In
      looking for mechanisms underlying these performance deficits, we have assessed
      adult neurogenesis in the dentate gyrus of Ts65Dn. Under untreated conditions,
      Ts65Dn mice (2-5 months old) showed markedly fewer BrdU-labeled cells than
      euploid animals. Chronic antidepressant treatment for over 3 weeks with the
      serotonin selective reuptake inhibitor, fluoxetine, increased neurogenesis in the
      Ts65Dn to comparable levels seen in the euploid by augmenting both proliferation
      and survival of BrdU-labeled cells in the subgranular layer and granule cell
      layer of the hippocampus, respectively.

PMID- 16624294
TI  - Matrix metalloproteinase activation and blood-brain barrier breakdown following
      thrombolysis.
AB  - Thrombolysis with tissue plasminogen activator (tPA) is the only pharmacotherapy
      available for cerebral ischemia. However, the use of tPA can increase the risk of
      hemorrhage due to blood-brain barrier (BBB) breakdown. Recent evidence suggests
      that increased activation of matrix metalloproteinases (MMPs) may be involved in
      this breakdown. This study examines the temporal profile of MMP-2 and -9
      following tPA administration to ischemic rats. Male Sprague-Dawley rats were
      randomly assigned to one of four groups (Sham-tPA; Sham-Saline; Ischemia-tPA;
      Ischemia-Saline; group n = 6, total N = 120). Focal embolic ischemia was induced
      by middle cerebral artery occlusion through injection of an autologous clot. One
      hour post-surgery, tPA (10 mg/kg) or saline was delivered intravenously and
      animals were euthanized at 3, 6, 12, or 24 h after onset of ischemia. Infarct
      volume was measured by TTC staining; BBB components examined
      immunohistochemically; and MMP activation measured by gelatin zymography. Our
      results show that tPA significantly reduced infarct volumes (overall infarct
      volume-Sham-tPA: 5.80 +/- 4.55 [mean +/- SE]; Sham-Saline: 5.00 +/- 4.23;
      Ischemia-tPA: 186.1 +/- 73.45; Ischemia-Saline: 284.8 +/- 88.74; all P < 0.05).
      Treatment with tPA was also associated with the activation of MMP-9 at 6, 12, and
      24 h following ischemia. No temporal changes were observed in MMP-2 activation,
      although tPA administration increased its activity compared to saline treatment.
      Analyses of immunohistochemistry showed that destruction of components of the BBB
      followed MMP-9 activation. Thus, increased MMP-9 activation may, in part, be
      responsible for the increases in hemorrhagic transformation reported with use of
      tPA. Our study is the first to demonstrate the temporal profile of MMP activation
      following thrombolysis with tPA in a model of thrombotic focal cerebral ischemia.

PMID- 16624295
TI  - Deoxycorticosterone's anticonvulsant effects in infant rats are blocked by
      finasteride, but not by indomethacin.
AB  - Deoxycorticosterone (DOC) is a steroid hormone that suppresses seizures in both
      humans and animals. At higher doses, DOC's anticonvulsant actions are accompanied
      by sedation and ataxia. The mechanism of DOC's anticonvulsant actions is not
      known, although it has been suggested that they may relate to DOC's secondary
      metabolite 3-alpha-5-alpha-tetrahydrodeoxycorticosterone (THDOC). The present
      study was designed to study the relation of DOC's anticonvulsant actions to its
      primary and secondary metabolites in 15-day-old rats. It was found that DOC's
      anticonvulsant and ataxic effects were suppressed by finasteride, which blocks
      the formation of DOC's primary metabolite, 3-alpha-5-alpha
      dehydrodeoxycorticosterone (DHDOC). They were not suppressed by indomethacin
      (INDO), which blocks the conversion of DHDOC into THDOC. The direct
      anticonvulsant effects of DHDOC and THDOC were also tested. DHDOC and THDOC were
      both potent anticonvulsants in 15-day old rats. Both also caused ataxia at high
      doses. DHDOC had a therapeutic index (TI) of 3.2, however, which was better than
      either DOC (TI = 1.2) or THDOC (TI = 1.5). It appears that DOC itself is not
      anticonvulsant, but that its anticonvulsant effects may relate to both its
      primary and secondary metabolites. DOC's primary metabolite, DHDOC--with its good
      TI--deserves a test in the treatment of childhood seizures.

PMID- 16624296
TI  - Neuronal apoptosis, metallothionein expression and proinflammatory responses
      during cerebral malaria in mice.
AB  - BACKGROUND: Cerebral malaria (CM) is an acute encephalopathy in humans due to the
      infection with Plasmodium falciparum. Neuro-cognitive impairment following CM
      occurs in about 10% of the treated survivors, while the precise
      pathophysiological mechanism remains unknown. Metallothionein I + II (MT-I + II)
      are increased during CNS pathology and disorders. As previously shown, MT-I + II
      are neuroprotective through anti-inflammatory, antioxidant and antiapoptotic
      functions. We have analyzed neuronal apoptosis and MT-I + II expression in brains
      of mice with experimental CM. METHODS: C57BL/6j mice, infected with Plasmodium
      berghei ANKA, were studied on day 7, day 9, and when presenting signs of CM on
      days 10-12. We investigated brain histopathology by immunohistochemistry and
      TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine
      triphosphate (dUTP)-digoxigenin nick end labeling). For statistics, we used
      quantitation (cellular counts) of the analyzed variables. RESULTS: During CM, we
      observed significant inflammatory responses of F4/80+ microglia/macrophages and
      GFAP+ reactive astrocytes and increased immunoreactivity of 8-oxoguanine (marker
      of oxidative stress). As novel findings, we show: (1) a localized CM-induced
      neuronal apoptosis (detected by TUNEL) indicating severe and irreversible
      pathology. (2) A significant increase in MT-I + II expression in reactive
      astrocytes, macrophages/microglia and vascular endothelium. INTERPRETATION: This
      is the first report showing apoptosis of neurons in CM by TUNEL, pointing out a
      possible pathophysiological mechanism leading to persisting brain damage. The
      possible neuroprotective role of MT-I + II during CM deserves further attention.

PMID- 16624297
TI  - Impairment of dentate gyrus neuronal progenitor cell differentiation in a mouse
      model of temporal lobe epilepsy.
AB  - Unilateral intrahippocampal injection of kainic acid (KA) in adult mice induces
      an epileptic focus replicating major histopathological features of temporal lobe
      epilepsy (TLE). In this model, neurogenesis is impaired in the lesioned dentate
      gyrus, although cell proliferation transiently is increased bilaterally in the
      subgranular zone (SGZ). To investigate further the relationship between
      epileptogenesis and neurogenesis, we compared the differentiation of cells born
      shortly before and after KA injection. Immunohistochemical staining for
      doublecortin and PSA-NCAM, two markers of young neurons, revealed a rapid
      downregulation of both markers ipsilaterally, whereas they were increased
      transiently on the contralateral side. To determine whether KA treatment directly
      affects neural progenitors in the SGZ, dividing cells were prelabeled with 5'
      bromo-2'deoxyuridine (BrdU) treatment before unilateral injection of KA. Double
      staining with the proliferation marker PCNA showed that prelabeled BrdU cells
      survived KA exposure and proliferated bilaterally. Unexpectedly, the neuronal
      differentiation of these cells, as assessed after 2 weeks with doublecortin and
      NeuN triple-staining, occurred to the same extent as on the contralateral side.
      Only 5% of pre-labeled BrdU cells were GFAP-positive within the lesion.
      Therefore, SGZ progenitor cells committed to a neuronal phenotype before KA
      treatment complete their differentiation despite the rapid down-regulation of
      doublecortin and PSA-NCAM. These findings suggest impaired fate commitment and/or
      early differentiation of proliferating cells in the lesioned dentate gyrus. Loss
      of neurogenesis in this TLE model likely reflects an irreversible alteration of
      the SGZ germinal niche during development of the epileptic focus and may
      therefore be relevant for human TLE.

PMID- 16624298
TI  - Bcl-xL and caspase inhibition increase the survival of rat oxytocin and
      vasopressin magnocellular neurons in organotypic culture.
AB  - Hypothalamic magnocellular neurons (MCNs) are highly vulnerable to axotomy
      induced cell death in vivo and in vitro. In this study, we determined whether the
      anti-apoptotic agent Bcl-xL, a member of the Bcl-2 family which prevents
      programmed cell death in the central nervous system, can rescue oxytocin (OT) and
      vasopressin (VP) MCNs in the supraoptic nucleus (SON) in organotypic culture. We
      found that the novel, membrane permeant form of Bcl-xL that we employed in these
      studies protected both OT and VP MCNs from degeneration as long as the Bcl-xL was
      present in the medium. In contrast, z-VAD-fmk, an inhibitor of caspases that are
      involved in apoptosis, was less effective in that it significantly rescued OT
      MCNs (P < 0.01) but not VP MCNs (P > 0.09). Unlike the Bcl-xL, Z-VAD-fmk's
      effectiveness in reducing MCN cell death was not sustained for the full 15 days
      in vitro.

PMID- 16624299
TI  - Delayed treatment with Rho-kinase inhibitor does not enhance axonal regeneration
      or functional recovery after spinal cord injury in rats.
AB  - Axonal regeneration in the central nervous system is blocked by many different
      growth inhibitory factors. Some of these inhibitors act on neurons by activating
      RhoA and Rho-kinase, an effector of RhoA. Several studies have shown that Rho
      kinase inhibition immediately after spinal cord injury enhances axonal sprouting
      and functional recovery. In this study, we ask whether delayed treatment with Rho
      kinase inhibitor is effective in promoting regeneration and functional recovery.
      We administered Fasudil, a Rho-kinase inhibitor, locally to the injury site 4
      weeks or immediately after contusion of the thoracic spinal cord in rats.
      Although the immediate treatment significantly stimulated axonal sprouting and
      recovery of hindlimb function, treatment started 4 weeks after surgery had no
      effect on fiber sprouting or locomotor recovery. Our findings suggest that
      RhoA/Rho-kinase alone may not account for the irreversible arrest of axon
      outgrowth in the chronic stage of injury in the central nervous system.

PMID- 16624300
TI  - Fear state induced by ethanol withdrawal may be due to the sensitization of the
      neural substrates of aversion in the dPAG.
AB  - The neural substrate underlying the aversive effects induced by ethanol
      abstinence is still unclear. One candidate for such effects is the dorsal
      periaqueductal gray (dPAG), a core structure of the brain aversion system. The
      main aim of this study is to examine the role of the dPAG as a possible locus of
      the aversive effects following abrupt alcohol withdrawal. To this end, rats were
      subjected to an oral ethanol self-administration procedure, in which animals were
      offered 6-8% (v/v) ethanol solution for a period of 21 days followed by an abrupt
      discontinuation of the treatment on the two subsequent days. Control animals
      received control dietary fluid for similar periods of time. The effects of
      ethanol withdrawal were examined in the elevated plus-maze (EPM) (Exp. I), on the
      prepulse inhibition of startle to loud sounds (Exp. II) and on the freezing and
      escape responses induced by electrical stimulation of the dPAG (Exp. III). In
      Experiment III, rats were implanted with an electrode aimed at the dPAG and the
      number and duration of ultrasonic vocalizations (USVs) were also recorded in the
      rats that received dPAG stimulation at freezing and escape thresholds. Data
      obtained showed that ethanol withdrawal elicited significant "anxiety-like"
      behaviors, as revealed by the decrease in the number of entries into and time
      spent onto the open arms of the EPM. Startle reflex and prepulse inhibition
      remained unchanged in withdrawn animals. In addition, discontinuation from the
      chronic ethanol regimen caused a reduction in the stimulation thresholds for
      freezing and escape and in the number and duration of USVs. Together, these
      effects have been interpreted in the frame of a high fear state elicited by
      activation of the dPAG. These findings are indicative that ethanol withdrawal
      sensitizes the substrates of fear at the level of this midbrain structure.

PMID- 16624301
TI  - Pivotal involvement of neurogenic mechanism in subcutaneous bee venom-induced
      inflammation and allodynia in unanesthetized conscious rats.
AB  - The bee venom (BV) model is a valid inflammatory pain model in animals and has
      been extended to human studies using its principle protein, mellitin. After
      subcutaneous (s.c.) injection of BV, long-lasting spontaneous nociception
      followed by thermal hyperalgesia, static allodynia, and local inflammatory
      response (edema) can be observed in rats. We hypothesize that (1) neurogenic
      components may contribute to the BV-induced inflammatory response and (2) static
      and dynamic mechanical allodynia may exist simultaneously in the BV model. Using
      different approaches including sciatic nerve transection (SCT), L4-L6 dorsal
      rhizotomy (DRT) and local treatment of the sciatic nerve with capsaicin, we found
      that SCT, DRT, and local capsaicin onto the sciatic nerve produced a significant
      inhibition of the BV-induced increase in volume of the injected paw, with a
      stronger effect of the SCT and the local capsaicin treatments than that of the
      DRT treatment. Static and dynamic mechanical allodynia in the BV test was
      assessed by measuring the paw withdrawal mechanical threshold and the paw
      withdrawal latency before and after the BV injection, respectively. Local
      capsaicin onto the sciatic nerve produced a significant inhibition of the BV
      induced decrease in the paw withdrawal mechanical threshold, but not the paw
      withdrawal latency, of the injected paw. These findings suggest that neurogenic
      components, via dorsal root reflex and axon reflex mechanisms, are probably
      involved in the maintenance and the development of the BV-induced inflammation.
      In addition, the capsaicin-sensitive primary afferents may play differential
      roles in the development of the BV-induced static and dynamic mechanical
      allodynia.

PMID- 16624302
TI  - Interruption of functional recovery by the NMDA glutamate antagonist MK801 after
      compression of the sensorimotor cortex: implications for treatment of tumors or
      other mass-related brain injuries.
AB  - Glutamate antagonists have recently been shown to limit tumor growth, providing
      potential new therapeutic targets and strategies against brain tumors. Here, we
      demonstrate that the glutamate NMDA receptor antagonist MK801, after a delay,
      adversely reverses functional recovery in rats with compressive mass lesions of
      the sensorimotor cortex. Our data suggest that the controlled focal cortical
      compression model may be a valuable pre-clinical tool to screen compounds for the
      treatment of brain tumors. It may be possible to use this model to develop
      interventions that maintain anti-cancer effects but with diminished harm to
      bystander tissue and brain plasticity.

PMID- 16624303
TI  - Mapping cellular gains and losses in the postnatal dentate gyrus: implications
      for psychiatric disorders.
AB  - Neurogenesis and apoptosis occur contemporaneously in the postnatal hippocampal
      dentate gyrus and have been implicated in mood and cognitive disorders.
      Particularly, neurogenesis correlates with the manifestation of antidepressant
      effects, but its quantitative and topographical relationship with concomitant
      cell death has not been investigated. Accordingly, we applied stereological
      measurements to obtain synchronized topographical maps of these two events in
      rats aged 1 and 3 months under basal conditions; the two ages were chosen to
      represent neuro-developmental windows during which cell proliferation and death
      are occurring at peak and relatively steady levels, respectively. Our analysis
      shows that apoptotic cells are evenly distributed throughout the dentate gyrus,
      although the incidence of apoptosis decreased gradient-wise from the tip of the
      suprapyramidal layer and was highest in the external third of the granule cell
      layer. Interestingly, apoptosis was higher in the left hippocampus. In addition,
      we confirm previous less stringent studies demonstrating that neurogenesis occurs
      differentially in the dorsal-ventral axis of the hippocampus and in
      suprapyramidal-infrapyramidal blades of the dentate gyrus. These results raise
      intriguing new questions regarding the coordinated regulation of hippocampal
      neurogenesis and apoptosis since the two processes apparently share common
      regulatory factors. In addition, these findings open questions with respect to
      the functional significance of topographical gradients in neurogenesis and
      apoptosis in the context of the etiopathogenesis of neuropsychiatric diseases and
      the reported dependence on the efficacy of therapeutic agents on the generation
      of new hippocampal neurons.

PMID- 16624304
TI  - Brain damage in neonatal rats following kaolin induction of hydrocephalus.
AB  - Neonatal and congenital hydrocephalus are common problems in humans.
      Hydrocephalus was induced in 1-day-old rats by injection of kaolin into the
      cisterna magna. At 7 and 21 days, magnetic resonance (MR) imaging was used to
      assess ventricle size, then brains were subjected to histopathological and
      biochemical analyses. Hydrocephalic pups did not exhibit delays in righting or
      negative geotaxis reflexes during the first week. At 7 days, there was variable
      ventricular enlargement with periventricular white matter edema, axon damage,
      reactive astrogliosis, and accumulation of macrophages in severe but not mild
      hydrocephalus. Cellular proliferation in the subependymal zone was significantly
      reduced. The cortical subplate neuron layer was disrupted. In rats allowed to
      survive to 21 days, weight was significantly lower in severely hydrocephalic
      rats. They also exhibited impaired memory in the Morris water maze test. Despite
      abnormal posture, there was minimal quantitative impairment of walking ability on
      a rotating cylinder. At 21 days, histological studies showed reduced corpus
      callosum thickness, fewer mature oligodendrocytes, damaged axons, and
      astroglial/microglial reaction. Reduced myelin basic protein, increased glial
      fibrillary acidic protein, and stable synaptophysin content were demonstrated by
      immunochemical methods. In conclusion, impairment in cognition and motor skills
      corresponds to ventricular enlargement and white matter destruction. Quantitative
      measures of weight, memory, ventricle size, and myelin, and glial proteins in
      this neonatal model of hydrocephalus will be useful tools for assessment of
      experimental therapeutic interventions.

PMID- 16624305
TI  - Estradiol-associated variation in responses of rostral medullary neurons to
      somatovisceral stimulation.
AB  - The lordosis posture and cervix stimulation during copulation are important
      reproductive events involving complex neural circuitries that are under hormonal
      influence. An important component of this circuitry, neurons within the medullary
      reticular formation (MRF), was examined in the present study using
      electrophysiological techniques. Single unit extracellular recordings were
      performed in the MRF of 27 urethane-anesthetized female rats. Using bilateral
      electrical stimulation of the dorsal nerve of the clitoris as the search
      stimulus, a detailed examination of the somatovisceral convergent responses of
      585 individual MRF neurons was made. A total of 7 different groups of cycling and
      ovariectomized/hormone-supplemented rats were examined and their neuronal
      response properties to mechanical stimulation of various pelvic organs (cervix
      pressure, vaginal distension, colon distension) compared. The results indicate
      the existence of complex response properties as well as several variations in MRF
      response characteristics that are hormone-dependent. Specifically, estradiol is
      associated with hyposensitivity to cervix pressure and hypersensitivity to
      stroking the face. These opposing effects of estradiol in the same subset of
      neurons likely relate to lordosis behavior which can be either disrupted or
      elicited, depending on the area being stimulated (upper versus lower parts of the
      body, respectively).

PMID- 16624306
TI  - Fetal fornix transection and gestation length in sheep.
AB  - Experiments in several species indicate that the hippocampus influences
      hypothalamo-pituitary-adrenal (HPA) axis function. In fetal sheep, simultaneous
      ACTH and cortisol rises over the last 30 days of gestation peak at term and are
      necessary for birth. We hypothesized that if the fetal hippocampal formation is
      functional in late gestation, loss of hippocampal input to the HPA axis following
      fetal fornix transection would change gestation length in comparison to controls.
      At 118-121 days of gestation (dG), stereotaxic technique was used in fetal sheep
      to sham transect (SHAM; n = 8) or transect (FXTX; n = 6) the dorsal fornix at the
      level of the hippocampal commissure. No differences were found between SHAM and
      FXTX fetuses in daily hormone profiles over the last week of gestation or in
      gestation length (148.0 +/- 1.2 vs. 149.0 +/- 0.4 dG, respectively). We conclude
      that the fetal hippocampus is immature in late gestation and we speculate that an
      immature hippocampus is necessary for the loss of negative feedback control that
      gives rise to the long term, simultaneous increases in ACTH and cortisol that are
      indispensable for labor and delivery at term in sheep.

PMID- 16624307
TI  - Plasmodium vinckei: selection of a strain exhibiting stable resistance to
      arteether.
AB  - A strain of rodent malaria parasite Plasmodium vinckei showing >12-fold
      resistance to arteether has been selected after exposure to sub-curative doses of
      drug in 44 sequential passages over a period of 700 days. Experimentally induced
      resistance was found to be stable after drug free maintenance of parasites for 11
      serial passages over a period of 100 days. Cross-sensitivity studies have shown
      that apart form resistance to related derivatives like artemether and artesunic
      acid, the derived parasites also show resistance to quinine and mefloquine.

PMID- 16624308
TI  - Trypanosoma evansi: genetic variability detected using amplified restriction
      fragment length polymorphism (AFLP) and random amplified polymorphic DNA (RAPD)
      analysis of Kenyan isolates.
AB  - We compared two methods to generate polymorphic markers to investigate the
      population genetics of Trypanosoma evansi; random amplified polymorphic DNA
      (RAPD) and amplified restriction fragment length polymorphism (AFLP) analyses.
      AFLP accessed many more polymorphisms than RAPD. Cluster analysis of the AFLP
      data showed that 12 T.evansi isolates were very similar ('type A') whereas 2
      isolates differed substantially ('type B'). Type A isolates have been generally
      regarded as genetically identical but AFLP analysis was able to identify multiple
      differences between them and split the type A T. evansi isolates into two
      distinct clades.

PMID- 16624309
TI  - Rhipicephalus (Boophilus) microplus (Canestrini, 1887) (Acari: Ixodidae): acid
      phosphatase and ATPase activities localization in salivary glands of females
      during the feeding period.
AB  - This study investigates the presence and the localization of acid phosphatase and
      ATPase in the salivary glands of Rhipicephalus (Boophilus) microplus female ticks
      during feeding. Semi-engorged females showed a larger amount of acid phosphatase
      compared to those at beginning of feeding, localized mainly in the apical portion
      of the secretory cells, and in the basal labyrinth of the interstitial cells.
      Ultrastructural observations also demonstrated its presence in secretion granules
      and inside some nuclei of secretory cells at beginning of feeding. Acid
      phosphatase in a free form probably has a hemolymph and/or ribosomal origin and
      participates in salivary gland secretion control. ATPase was detected in basal
      membrane of all types of acini and/or in the cytoplasm of the secretory cells at
      both feeding stages. The enzyme activities found strongly suggests that cell
      death by apoptosis occurs during the degenerative process.

PMID- 16624310
TI  - Effects of cyclic nucleotides, calcium ionophore, and phorbol ester on
      vitellogenin mRNA levels in incubated ovarian fragments of the kuruma prawn
      Marsupenaeus japonicus.
AB  - In crustaceans, vitellogenin (VTG, the precursor of major yolk protein) is
      synthesized in the ovary and/or hepatopancreas, and its synthesis is considered
      to be under the negative control of the vitellogenesis-inhibiting hormone (VIH),
      a neuropeptide secreted from the X-organ/sinus gland complex in the eyestalks. In
      the present study, the effects of pharmacological agents on VTG mRNA levels in
      incubated ovarian fragments of the kuruma prawn Marsupenaeus japonicus were
      examined to determine the intracellular signalling pathways for VTG synthesis.
      After 24 h incubation, A23187 (calcium ionophore), dibutyl-cAMP (cAMP analogue),
      dibutyl-cGMP (cGMP analogue), forskolin (adenylate cyclase activator), 3-isobutyl
      1-methylxanthine (IBMX, phosphodiesterase inhibitor), and phorbol 12-myristate 13
      acetate (PMA, protein kinase C activator) decreased VTG mRNA levels in the
      ovarian fragments. This result suggests that cyclic nucleotides, Ca2+, and
      protein kinase C are involved in the signalling pathways for the regulation of
      VTG mRNA levels in the ovaries. Furthermore, the inhibitory effects of sinus
      gland extract and the pharmacological agents on VTG mRNA were larger in
      previtellogenic ovaries than in vitellogenic ovaries. This result suggests that
      the degree of responsiveness to VIH changes during ovarian development and that
      the changes in responsiveness to VIH involve maturity-related changes in cellular
      signalling mechanisms in the ovaries.

PMID- 16624311
TI  - Actions of glucocorticoids at a seasonal baseline as compared to stress-related
      levels in the regulation of periodic life processes.
AB  - For decades, demands associated with the predictable life-history cycle have been
      considered stressful and have not been distinguished from stress that occurs in
      association with unpredictable and life-threatening perturbations in the
      environment. The recent emergence of the concept of allostasis distinguishes
      behavioral and physiological responses to predictable routines as opposed to
      unpredictable perturbations, and allows for their comparison within one
      theoretical framework. Glucocorticosteroids (GCs) have been proposed as important
      mediators of allostasis, as they allow for rapid readjustment and support of
      behavior and physiology in response to predictable and unpredictable demands
      (allostatic load). Much work has already been done in defining GC action at the
      high concentrations that accompany life-threatening perturbations. However, less
      is known about the role of GCs in relation to daily and seasonal life processes.
      In this review, we summarize the known behavioral and physiological effects of
      GCs relating to the predictable life-history cycle, paying particular attention
      to feeding behavior, locomotor activity and energy metabolism. Although we
      utilize a comparative approach, emphasis is placed on birds. In addition, we
      briefly review effects of GCs at stress-related concentrations to test the
      hypothesis that different levels of GCs play specific and distinct roles in the
      regulation of life processes and, thus, participate in the promotion of different
      physiological states. We also examine the receptor types through which GC action
      may be mediated and suggest mechanisms whereby different GC concentrations may
      exert their actions. In conclusion, we argue that biological actions of GCs at
      "non-stress" seasonal concentrations play a critical role in the adjustment of
      responses that accompany predictable variability in the environment and demand
      more careful consideration in future studies.

PMID- 16624312
TI  - Age-related variation in the adrenocortical response to stress in nestling white
      storks (Ciconia ciconia) supports the developmental hypothesis.
AB  - The post-natal development of the adrenocortical response to stress was
      investigated in European white storks. Sixty wild nestlings aged 24-59 days old
      were subjected to a standardized capture and restraint protocol, and the time
      course pattern of the response to stress was assessed through determination of
      circulating corticosterone in blood samples collected at five fixed times during
      the 45-min period following capture. The time course of the response was best fit
      to a third-order function of handling time, and showed a strong effect of age.
      Although age did not affect baseline titers and all birds showed a positive post
      capture increase in circulating corticosterone, age had a positive effect on the
      relative increase from baseline titer, the recorded time to reach maximum level,
      and the acute concentration after 10 min following capture and restraint. While
      young nestlings displayed very little response to capture, the response near
      fledging resembled the typical adrenocortical pattern widely reported in fully
      developed birds. Our results concur with those found in altricial and semi
      altricial species, and suggest that non-precocial birds follow a similar mode of
      development of the hypothalamic-pituitary-adrenal (HPA) axis. The fact that HPA
      sensitivity to stress is functional suggests that young storks gradually develop
      emergency responses of adaptive value and are able to overcome acute
      perturbations in spite of their parental dependence, at least during the last two
      thirds of post-natal development. According to the Developmental Hypothesis, such
      gradual changes would allow nestlings to respond to perturbations as a function
      of the specific behavioral and physiological abilities of their age. The
      potential sources of stress that nestlings have to face during development (i.e.,
      weather conditions, dietary restrictions, and social competition) are discussed
      according to developmental changes in behavioral and physiological abilities.

PMID- 16624313
TI  - Cortisol and parathyroid hormone-related peptide are reciprocally modulated by
      negative feedback.
AB  - In previous in vitro studies, we have shown that the N-terminal region of
      parathyroid hormone-related protein (PTHrP) can stimulate cortisol production in
      sea bream, Sparus auratus, interrenal tissue, possibly through a paracrine
      action. In the current study, the systemic interaction between cortisol and PTHrP
      was studied in vivo. Sustained elevated blood cortisol levels, induced either by
      cortisol injection or confinement stress, suppressed circulating PTHrP 6 and 24
      fold, respectively, by comparison to control fish. Dexamethasone treatment
      reduced cortisol levels, prevented the decrease of plasma PTHrP observed in
      confined fish and raised plasma PTHrP levels in non-confined fish. In contrast, a
      single injection of (1-34) PTHrP caused a short-term (within 30 min and up to 2.5
      h) decrease in plasma cortisol. The antagonistic effects between PTHrP and
      cortisol were substantiated by an overall (data pooled from all experiments)
      highly significant negative correlation (r0=-0.745, p<0.001, n=115) between the
      plasma levels of the two hormones. Although the underlying mechanism of the
      interaction still has to be determined, the high levels of PTHrP in circulation
      and the existence of systemic regulation favour the hypothesis that in fish PTHrP
      may act as an endocrine factor, although the gland that produces it still remains
      to be identified.

PMID- 16624314
TI  - Population divergence in plasticity of the AVT system and its association with
      aggressive behaviors in a Death Valley pupfish.
AB  - Behavioral differences can evolve rapidly in allopatry, but little is known about
      the neural bases of such changes. Allopatric populations of Amargosa pupfish
      (Cyprinodon nevadensis) vary in aggression and courtship behaviors in the wild.
      Two of these wild populations were recently found to differ in brain expression
      of arginine vasotocin (AVT)--a peptide hormone shown previously to modulate
      aggression in pupfish. These populations have been isolated for less than 4000
      years, so it remained unclear whether the differences in behavior and neural AVT
      phenotype were evolved changes or plastic responses to ecologically dissimilar
      habitats. Here, I tested whether these population differences have a genetic
      basis by examining how aggressive behavior and neural AVT phenotype responded to
      ecologically relevant variation in salinity (0.4 ppt or 3 ppt) and temperature
      (stable or daily fluctuating). Pupfish from Big Spring were more aggressive than
      pupfish from the Amargosa River when bred and reared under common laboratory
      conditions. Morphometric analysis of preoptic AVT immunoreactivity showed that
      the populations differed in how the AVT system responded to salinity and
      temperature conditions, and revealed that this plasticity differed between
      parvocellular and magnocellular AVT neuron groups. Both populations also showed
      relationships between neural AVT phenotype and aggression in the rearing
      environment, although populations differed in how aggression related to variation
      in magnocellular AVT neuron size. Together, these results demonstrate that the
      pupfish populations have diverged in how physical and social conditions affect
      the AVT system, and provide evidence that the AVT system can evolve quickly to
      ecologically dissimilar environments.

PMID- 16624315
TI  - Androgens and autistic traits: A study of individuals with congenital adrenal
      hyperplasia.
AB  - Testosterone promotes male-typical neural and behavioral development in non-human
      mammals. There is growing evidence that testosterone exerts similar influences on
      human development, although the range of behaviors affected is not completely
      known. This study examined the hypothesis that autistic traits are increased
      following prenatal exposure to abnormally high levels of testosterone caused by
      congenital adrenal hyperplasia (CAH). Sixty individuals with CAH (34 female, 26
      male) and 49 unaffected relatives (24 female, 25 male) completed the Autism
      Spectrum Quotient (AQ). Females with CAH scored significantly higher than
      unaffected females on total AQ score, largely due to enhanced scores on subscales
      measuring social skills and imagination. These results suggest that prenatal
      exposure to high levels of testosterone influences some autistic traits and that
      hormonal factors may be involved in vulnerability to autism.

PMID- 16624316
TI  - Trauma case management: improving patient outcomes.
AB  - BACKGROUND: The purpose of the study was to measure the effect of trauma case
      management (TCM) on patient outcomes, using practice-specific outcome variables
      such as in-hospital complication rates, length of stay, resource use and allied
      health service intervention rates. METHODS: TCM was provided 7 days a week to all
      trauma patient admissions. Data from 754 patients were collected over 14 months.
      These data were compared with 777 matched patients from the previous 14 months.
      RESULTS: TCM greatly improved time to allied health intervention (p<0.0001).
      Results demonstrated a decrease in the occurrence of deep vein thrombosis
      (p<0.038) and a trend towards decreased patient morbidity, unplanned admissions
      to the intensive care unit and operating suite. A reduced hospital stay LOS,
      particularly in the paediatric and 45-64 years age group was noted. Six thousand
      six hundred twenty-one fewer pathology tests were performed and the total number
      of bed days was 483 days less than predicted from the control group. CONCLUSION:
      The introduction of TCM improved the efficiency and effectiveness of trauma
      patient care in our institution. This initiative demonstrates that TCM results in
      improvements to quality of care, trauma patient morbidity, financial performance
      and resource use.

PMID- 16624317
TI  - Impaired postprandial apolipoprotein-B48 metabolism in the obese, insulin
      resistant JCR:LA-cp rat: increased atherogenicity for the metabolic syndrome.
AB  - AIM: Postprandial lipaemia is a significant contributor to the development of
      dyslipidaemia and cardiovascular disease, which has more recently been shown as a
      potential risk factor for obesity and pre-diabetes. Clinically however, the
      diagnosis of early insulin-resistance remains confounded due to the fact that
      aberrations in lipid metabolism are not often readily identified using classic
      indicators of hypercholesterolemia (i.e. LDL). METHODS: In this study, we
      assessed the metabolism of apolipoprotein-B48 (apoB48)-containing lipoproteins in
      an animal model of obesity and insulin-resistance, the JCR:LA-cp rat. The
      contribution of lipoproteins from the intestine was assessed by measuring plasma
      apoB48 concentration in the postprandial period following an oral fat load.
      Plasma apoB48 was measured by improved enhanced chemiluminescent detection and
      other biochemical parameters measured by established analysis. RESULTS: Fasting
      concentrations of plasma apoB48, postprandial apoB48 area under the curve (AUC),
      as well as incremental-AUC (iAUC), were all significantly greater in the obese
      phenotype compared to lean controls. Fasting apoB48 correlated significantly with
      apoB48-iAUC, triglyceride (TG)-iAUC and insulin-iAUC. In addition, there was a
      highly significant association with fasting insulin and the postprandial ratio of
      TG:apoB48, a relationship not often detected in humans during insulin-resistance.
      CONCLUSIONS/INTERPRETATION: We conclude that the JCR:LA-cp rat can be used as a
      model of postprandial lipemia to explore chylomicron metabolism during the onset
      and development of insulin-resistance, including the increased cardiovascular
      complications of the metabolic syndrome.

PMID- 16624318
TI  - Evaluation of a 3D object registration method for analysis of humeral kinematics.
AB  - In 3D image-based studies of joint kinematics, 3D registration methods should be
      automatic, insensitive to segmentation inconsistencies and use coordinate systems
      that have clinically relevant orientations and locations because this is
      important for analyzing rotation angles and translation directions. We developed
      and evaluated a registration method, which is based on the cylindrical geometry
      of the humerus shaft and an analysis of the inertia moments of the humerus head,
      in order to consistently and automatically orient the humerus coordinate system
      according to its anatomy. Registration techniques must be thoroughly evaluated.
      In this study we used a well-detectable marker as reference, from which
      coordinate system determination errors of a 3D object could be measured. This
      allowed us to quantify by means of unique error analysis the translational and
      rotational errors in terms of how much and about/along which humeral axis errors
      occurred. The evaluation experiments were performed using virtual rotations of 3D
      humeral binary image, a humerus model and a 3D image of a volunteer's shoulder.
      They indicated that the humeral coordinate system determination errors primarily
      originated from segmentation inconsistencies, which influenced mostly the humeral
      transverse axes orientation. The error analysis revealed that the developed
      registration method reduced the effect of manual segmentation inconsistencies on
      the orientation of the humeral transverse axes up to 37%, in comparison to the
      commonly used inertia registration.

PMID- 16624319
TI  - Anatomy and nomenclature of murine lymph nodes: Descriptive study and
      nomenclatory standardization in BALB/cAnNCrl mice.
AB  - Murine lymph nodes are intensively studied but often assigned incorrectly in
      scientific papers. In BALB/cAnNCrl mice, we characterized a total of 22 different
      lymph nodes. Peripheral nodes were situated in the head and neck region
      (mandibular, accessory mandibular, superficial parotid, cranial deep cervical
      nodes), and at the forelimb (proper axillary, accessory axillary nodes) and
      hindlimb (subiliac, sciatic, popliteal nodes). Intrathoracic lymph nodes included
      the cranial mediastinal, tracheobronchal and caudal mediastinal nodes. Abdominal
      lymph nodes were associated with the gastrointestinal tract (gastric,
      pancreaticoduodenal, jejunal, colic, caudal mesenteric nodes) or were located
      along the major intra-abdominal blood vessels (renal, lumbar aortic, lateral
      iliac, medial iliac and external iliac nodes). Comparative and nomenclative
      aspects of murine lymph nodes are discussed. The position of the lymph nodes of
      BALB/cAnNCrl mice is summarized and illustrated in an anatomical chart containing
      proposals for both an official nomenclature according to the Nomina Anatomica
      Veterinaria and English terms.

PMID- 16624320
TI  - Resin-based micropipette tip for immunochromatographic assays in urine samples.
AB  - A novel bioanalysis system based on immunochromatography was developed in
      connection with a nitrocellulose resin modified micropipette tip, such as ZipTip.
      The sandwich-type immunoassay was applied to our bioanalysis system. The simple
      handling of the micropipette enabled us to increase the sample volume and detect
      low concentrations of target antigens in urine samples. In addition, the washing
      procedure could also be performed easily to reduce the background signal levels.
      For analytical evaluations, the color intensity was captured by a flatbed
      scanner, and processed by a software. We have achieved the detection of human
      chorionic gonadotropin (hCG) and prostate-specific antigen (PSA). The detection
      limit of hCG was 0.5 ng/ml (0.05 ng/tip), which is comparable to that of other
      conventional immunochromatographic systems. Moreover, the detection of PSA was
      greatly improved over the existing systems with the application of different
      sample volumes, such as 1 ng/ml (0.2 ng/tip) in a 200 microl sample volume, and 1
      ng/ml (0.3 ng/tip) in 300 microl sample volume. Our bioanalysis system is a
      promising candidate for application to point-of-care tests with its simple
      handling and high sensitivity.

PMID- 16624321
TI  - Characterization of binding activity between nuclear factor of activated T cells
      and calcineurin by amplified luminescent proximity homogeneous assay.
AB  - For quantitative evaluation of the relationship between biological binding
      partners, including protein-protein interactions, a novel analyzing system,
      amplified luminescent proximity homogeneous assay (ALPHA), has been developed. We
      here employed ALPHA for accurate assessment of the binding properties between
      nuclear factor of activated T cells 1 (NFAT1) and calcineurin (CN), which is
      essential for Ca2+-dependent regulation of immune responses. A recombinant
      protein of the Ca2+ regulatory domain (CRD) of NFAT1 was prepared and its binding
      activity with biotinylated CN was determined by ALPHA (Kd = 0.20 microM). The
      contribution of each CN-binding component involved in the CRD of NFAT1 to
      CN/NFAT1 binding was next examined by competitive assay. Not only the whole CRD
      but also the N- and C-terminal CN-binding regions (CNBR1 and CNBR2, respectively)
      dose-dependently blocked CN/NFAT1 binding and their potency was CRD >> CNBR2 > or
      = CNBR1. CN/NFAT1-binding properties were further characterized using short
      inhibitory peptides derived from NFAT1-CNBR1 as well as NFAT4-CNBR2. In
      conclusion, ALPHA is a useful system to analyze biological signaling cascades,
      due to its capability of quantitative evaluation of protein-protein interactions.

PMID- 16624322
TI  - WHO/WFN Survey of neurological services: a worldwide perspective.
AB  - According to the findings obtained in the context of a Global Initiative on
      Neurology and Public Health carried out by the World Health Organization (WHO),
      there has been a lack of reliable and comparative data on services and other
      resources for neurological disorders in many parts of the world. In view of these
      findings and in collaboration with the World Federation of Neurology (WFN), WHO
      has recently organized an international Survey of Country Resources for
      Neurological Disorders, which involved 109 countries and covered over 90% of the
      world's population. This large WHO/WFN collaborative endeavour collected expert
      information on a number of aspects of neurological care provision around the
      world including availability of neurological services in primary care; human
      resources for neurological disorders; sub-specialized neurological services;
      primary method of financing of neurological care; and disability benefits for
      patients with neurological disorders. The WHO/WFN Survey results clearly
      demonstrate that there are inadequate resources for patients with neurological
      disorders in most parts of the world, and highlight inequalities in the access to
      neurological care across different populations, and in particular in those living
      in low-income countries and in developing regions of the world. The key findings
      of the WHO/WFN Survey including their impact on delivery of neurological care
      around the world are presented and discussed in this paper. The entire set of
      WHO/WFN Survey results including numerous tables, graphs and accompanying
      commentaries can be found in the WHO/WFN Atlas of Country Resources for
      Neurological Disorders, which is available on request from WHO or at
      http://www.who.int/mental_health/neurology/ .

PMID- 16624323
TI  - Investigation of Lewy pathology in the visual pathway of brains of dementia with
      Lewy bodies.
AB  - We examined 19 autopsied cases of dementia with Lewy bodies (DLB) using
      pathological and alpha-synuclein-immunohistochemical methods, and investigated
      Lewy pathology in the primary visual pathway (lateral geniculate body and
      Brodmann's area 17), secondary visual pathway (pulvinar, Brodmann's areas 18 and
      19, and inferior temporal cortex), amygdala and substantia nigra, to clarify the
      relationship between visual misidentification and Lewy pathology in the visual
      pathway. Consequently, the secondary visual pathway revealed significantly
      severer Lewy pathology than the primary visual pathway, suggesting that the
      degeneration of the secondary visual pathway induces dysfunction in the
      recognition of objects shape and color. In addition, the amygdala revealed
      significantly severer Lewy pathology and neuronal loss than the primary and
      secondary visual pathways, suggesting that the degeneration of the amygdala,
      which receives the afferent connections from the substantia nigra, fails to
      modulate the visual processing according to cognition and emotion. These findings
      suggest that Lewy pathologies in the secondary visual pathway and amygdala may
      cause the dysfunction of the visuo-amygdaloid pathway and participate in visual
      misidentification in DLB patients. In addition, we compared Lewy pathology
      between cases with and without visual hallucinations, and showed no significant
      differences between the two groups.

PMID- 16624324
TI  - A stochastic model of gene transcription: an application to L1 retrotransposition
      events.
AB  - A simplified mathematical model of gene transcription is presented based on a
      system of coupled chemical reactions and a corresponding set of stochastic
      equations similar to those used in enzyme kinetics theory. The quasi-stationary
      distribution for the model is derived and its usefulness illustrated with an
      example of model parameters estimation using sparse time course data on L1
      retrotransposon expression kinetics. The issue of model validation is also
      discussed and a simple validation procedure for the estimated model is devised.
      The procedure compares model predicted values with the laboratory data via the
      standard Bayesian techniques with the help of modern Markov-Chain Monte-Carlo
      methodology.

PMID- 16624326
TI  - Evidence that triiodothyronine decreases rat serum leptin concentration by down
      regulation of leptin gene expression in white adipose tissue.
AB  - Conflicting results have been reported regarding the effect of triiodothyronine
      (T(3)) on serum leptin and adipose tissue leptin gene expression in human and
      animals. The aim of the present study was to evaluate the effect of
      administration of increasing doses of T(3) on serum leptin concentration and on
      leptin mRNA abundance in white adipose tissue of rats. The results presented in
      this paper indicate that administration of single different doses of T(3) to
      euthyroid rats resulted dose dependent increases of serum total T(3)
      concentrations which are associated with a decrease in white adipose tissue
      leptin mRNA level. The leptin mRNA level in white adipose tissue was negatively
      correlated with serum total T(3) concentration (r=-0.8, p<0.001). Like white
      adipose tissue leptin mRNA level, serum leptin concentration decreased after T(3)
      administration, and was also negatively correlated with the serum T(3)
      concentration (r=-0.8, p<0.001). In contrast, administration of T(3) to the same
      rats led to a significant increase in white adipose tissue expression of the
      malic enzyme gene (malic enzyme activity and malic enzyme mRNA level), a known
      target gene for T(3). The results indicate that T(3) exerts a selective
      inhibitory effect on white adipose tissue leptin gene expression in vivo. A
      conclusion is that T(3) decreases rat serum leptin concentration by down
      regulation of leptin gene expression in white adipose tissue.

PMID- 16624325
TI  - Effects of salt loading and various therapies on cardiac hypertrophy and fibrosis
      in young spontaneously hypertensive rats.
AB  - We investigated the effects of salt loading on blood pressure, cardiac
      hypertrophy and fibrosis as well as on the effectiveness of various
      antihypertensive therapies in young spontaneously hypertensive rats (SHR). Twenty
      five male SHR were salt-stimulated by drinking 1% NaCl from 3 to 6 months of age.
      Eighteen of them were treated for the last 2 weeks of salt loading with either
      the angiotensin-converting enzyme inhibitor captopril, the beta-adrenergic
      receptor blocker propranolol or the calcium-channel antagonist verapamil. Age
      matched male Wistar-Kyoto (WKY) rats and SHR drinking only water served as
      controls. At the age of 6 months, SHR had significantly elevated blood pressure
      that was unchanged by salt loading. Relative heart weight was increased in SHR
      without (3.3) and even more so with salt intake (3.6 vs. 2.4 in WKY). Left
      ventricular (LV) hypertrophy was accompanied by a 17-fold increase in the
      expression of mRNA for atrial natriuretic factor (ANF) both in untreated and salt
      loaded SHR compared to WKY (p<0.001). Collagen I and III mRNA increased 1.7-1.8
      fold in SHR without and with additional salt intake (p<0.01). None of the
      therapies significantly reduced blood pressure or hypertrophy. Although captopril
      had no antihypertensive effect, it reduced ANF, collagen I and III mRNA in LV to
      control level. Less pronounced effects were achieved with verapamil. These
      findings emphasize the cardioprotective role of captopril which may not be fully
      expressed in the presence of elevated salt intake.

PMID- 16624327
TI  - Immobility response elicited by clamping the neck induces antinociception in a
      "tonic pain" test in mice.
AB  - Clamping the neck followed by body inversion to a supine position in mice elicits
      an immobility response called immobility by clamping the neck (ICN). The noxious
      pinch to the scruff of the neck produces antinociception in "phasic pain" models
      (e.g. tail-flick test). Here, a "tonic pain" model was used to test the
      antinociception associated with the ICN, and naloxone was used to determine the
      role of opioids in such antinociception. Mice were injected intraperitoneally
      with 0.3 mL of 0.4% acetic acid to produce writhing responses that were measured
      for one hour. ICN was induced every five minutes for one hour. Naloxone (5 mg/kg
      ip) was injected 10 min before acetic acid administration. There was a control
      group, sham clamping (SCLA). These mice were handled and restricted every five
      minutes as in the ICN but without real clamping. The repetitive inductions of ICN
      were able to reduce the writhing behavior; this antinociception was blocked by
      the naloxone pretreatment. In the SCLA group antinociception was not observed.
      These findings indicate that as in the "phasic pain" model, ICN also was able to
      elicit antinociception in this "tonic pain" model, and such antinociception seems
      to be mediated by opioids.

PMID- 16624328
TI  - Exhaustion of the Frank-Starling mechanism in conscious dogs with heart failure
      induced by chronic coronary microembolization.
AB  - The role of the Frank-Starling mechanism in the regulation of cardiac systolic
      function in the ischemic failing heart was examined in conscious dogs. Left
      ventricular (LV) dimension, pressure and systolic function were assessed using
      surgically implanted instrumentations and non-invasive echocardiogram. Heart
      failure was induced by daily intra-coronary injections of microspheres for 3-4
      weeks via implanted coronary catheters. Chronic coronary embolization resulted in
      a progressive dilation of the left ventricle (12+/-3%), increase in LV end
      diastolic pressure (118+/-19%), depression of LV dP/dt(max) (-19+/-4%),
      fractional shortening (-36+/-7%), and cardiac work (-60+/-9%), and development of
      heart failure, while the LV contractile response to dobutamine was depressed. A
      brief inferior vena caval occlusion in dogs with heart failure decreased LV
      preload to match the levels attained in their control state and caused a further
      reduction of LV dP/dt(max), fractional shortening, stroke work and cardiac work.
      Moreover, in response to acute volume loading, the change in the LV end-diastolic
      dimension-pressure (DeltaLVEDD-DeltaLVEDP) curve in the failing heart became
      steeper and shifted significantly to the left, while the increases in LV stroke
      work and cardiac work were blunted. Thus, our results suggest that the Frank
      Starling mechanism is exhausted in heart failure and unable to further respond to
      increasing volume while it plays an important compensatory role in adaptation to
      LV dysfunction in heart failure.

PMID- 16624329
TI  - Run down of GABAergic depolarization during metabolic inhibition of rat
      hippocampal CA1 neurons.
AB  - We investigated the effects of metabolic inhibition on both the shift in the
      equilibrium potential for Cl(-) (E(Cl)) and the run down of GABA(A) receptor
      responses, using nystatin- and gramicidin-perforated patch-clamp recordings from
      rat hippocampal CA1 neurons. Metabolic inhibition with NaCN decreased outward
      GABAergic currents while increasing inward GABAergic currents. E(Cl) showed a
      positive shift almost immediately after metabolic poisoning. This shift always
      occurred prior to GABA receptor run down, which was observed as decreases in
      whole cell conductance during application of a GABA(A) receptor agonist. The
      results indicate that GABAergic responses tend to become depolarizing during
      metabolic inhibition and the run down of the GABAergic response may therefore be
      neuroprotective against excitotoxicity. Furthermore the results illustrate the
      importance of considering both changes in receptor function and current driving
      force, and their temporal relationship, in order to understand the physiological
      response of the GABAergic system during metabolic stress.

PMID- 16624330
TI  - Thiamine-like fibers in the monkey brain: an immunocytochemical study.
AB  - The distribution of thiamine-immunoreactive structures was studied in the brain
      of the monkey using an indirect immunoperoxidase technique. Fibers containing
      thiamine, but no thiamine-immunoreactive cell bodies, were found. The highest
      density of fibers containing thiamine was observed in the pulvinar nucleus and in
      the region extending from the pulvinar nucleus to the caudate nucleus. In the
      mesencephalon, immunoreactive fibers containing thiamine were only found at
      rostral level close to the medial lemniscus (at the mesencephalic-diencephalic
      junction). In the thalamus, the distribution of thiamine-immunoreactive
      structures was more widespread. Thus, immunoreactive fibers were found in nuclei
      close to the midline (centrum medianum/parafascicular complex), in the
      ventrolateral thalamus (medial geniculate nucleus, inferior pulvinar nucleus),
      and in the dorsolateral thalamus (lateral posterior nucleus, pulvinar nucleus).
      Finally, in the anterior commissure and in the cerebral cortex a low density
      immunoreactive fibers was visualized. Thus, in the brainstem, no immunoreactive
      structures were visualized in the medulla oblongata, pons, or in the medial
      caudal mesencephalon, and no immunoreactive fibers were observed in the
      cerebellum, hypothalamus and in the basal ganglia. The present report describes
      the first visualization and the morphological characteristics (thick, smooth and
      short, medium or long in length) of the thiamine-immunoreactive fibers in the
      primate central nervous system using an antiserum directed against this vitamin.
      The distribution of thiamine-immunoreactive structures in the monkey brain
      suggests that this vitamin could be involved in several physiological mechanisms.

PMID- 16624331
TI  - Cytoprotective effect of two synthetic enhancer substances, (-)-BPAP and (-)
      deprenyl, on human brain capillary endothelial cells and rat PC12 cells.
AB  - Enhancer regulation is a new control mechanism in the brain [Knoll, J., 2003.
      Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical
      concept of the innate and acquired drives. Neurochemical Research 28(8), 1275
      1297]. Enhancer substances exert their effect in bi-modal form with a highly
      characteristic dose-dependency. Two bell-shaped concentration curves have been
      published. The one in ultra low concentration range (fM) specific form of
      enhancer regulation and the other at high concentration (100 microM) non-specific
      form of enhancer regulation. Catecholaminergic neurons proved to be enhancer
      sensitive cells. Since rat PC12 cells and human brain endothelial cells (HBEC)
      work under catecholaminergic influence, it was reasonable to expect that both the
      specific and non-specific form of the enhancer regulation might be detectable in
      these cells. We tested this possibility on these cultured cells under normoxia
      and hypoxia-reoxygenation. After 1 h hypoxia produced by Argon gas and 0, 2, 4,
      and 20 h reoxygenation the cell loss was calculated by propidiumiodide assay and
      the cell activity was investigated by Alamar Blue assay colorimetric measurement.
      The percentages of living and necrotic cells were expressed after propidiumiodide
      staining. Broad scale concentrations of the two compounds (1 fM-100 microM) were
      added to the culture strait after the oxygen deprivation. (-)-BPAP and (-)
      deprenyl, due to their enhancer effect, exerted a significant cytoprotective
      effect on both HBECs and PC12 cells. In harmony with Knoll's publications we were
      able to demonstrate by the aid of (-)-BPAP and (-)-deprenyl that both HBEC and
      PC12 are enhancer-sensitive cells. We detected the specific form of the enhancer
      regulation in the ultra low concentration range (fM-pM) and also the non-specific
      form of the enhancer regulation was visible (mM-microM).

PMID- 16624332
TI  - High-fat emulsion-induced rat model of nonalcoholic steatohepatitis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is emerging as a common medical
      problem. Nonalcoholic steatohepatitis (NASH) is the critical turning point at
      which NAFLD progresses to more advanced stages such as hepatic fibrosis,
      cirrhosis and even hepatocellular carcinoma. However, the study of the pathogenic
      or therapeutic factors involved in NASH has been hampered by the absence of a
      suitable experimental model. The aim of the present work was to establish a high
      fat emulsion-induced rat model of NASH. Male Sprague-Dawley rats were fed a high
      fat emulsion via gavage for 6 weeks. Animals were examined for weight gain, serum
      and hepatic biochemistry, insulin sensitivity, hepatic malondialdehyde (MDA),
      superoxide dismutase (SOD) and tissue morphology, as well as cytochrome P-450 2E1
      (CYP2E1) and peroxisome proliferator-activated receptor alpha (PPARalpha)
      expression in the liver. The results showed that rats treated with high-fat
      emulsion became obese, demonstrated abnormal aminotransferase activity,
      hyperlipoidemia, hyperinsulinemia, hyperglycemia and insulin resistance. The
      model rats exhibited an increased concentration of serum TNF-alpha, total
      cholesterol (TC), triglyceride (TG), MDA and reduced SOD levels in the liver.
      Immunoblot analysis showed that the expression of CYP2E1 was increased, whereas
      PPARalpha was reduced in the NASH model rat liver. Moreover, morphological
      evaluation revealed that hepatic steatosis, inflammation and mitochondrial
      lesions were also reproduced in this model. In conclusion, a practical and
      repeatable new rat model of steatohepatitis was established by feeding with high
      fat emulsion via gavage. This model provides a valuable research tool and
      reproduces many of the clinical indices of human NASH.

PMID- 16624333
TI  - [D-1-Nal4]endomorphin-2 is a potent micro-opioid receptor antagonist in the
      aequorin luminescence-based calcium assay.
AB  - A functional assay, based on aequorin-derived luminescence triggered by receptor
      mediated changes in Ca(2+) levels, was used to examine relative potency and
      efficacy of the micro-opioid receptor antagonists. A series of position 3- and 4
      substituted endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) analogues containing D-3-(1
      naphthyl)-alanine (D-1-Nal) or D-3-(2-naphthyl)-alanine (D-2-Nal), which were
      previously shown to reverse antinociception induced by endomorphin-2 in the in
      vivo hot-plate test in mice, was tested in the aequorin luminescence-based
      calcium assay to examine their micro-opioid antagonist potency in vitro. A
      recombinant mammalian cell line expressing the micro-opioid receptor together
      with a luminescent reporter protein, apoaequorin, was used in the study. The
      results obtained in this functional assay indicated that analogues with D-1-Nal
      or D-2-Nal substitutions in position 4 of endomorphin-2 are strong micro-opioid
      receptor antagonists, while those substituted in position 3 are partial agonists.
      Exceptional antagonist potency in the calcium assay was observed for [D-1
      Nal(4)]endomorphin-2. The pA(2) value for this analogue was 7.95, compared to the
      value of 8.68 obtained for the universal, non-selective opioid antagonist of the
      alkaloid structure, naloxone. The obtained results were compared with the data
      from the hot-plate test in mice. In that in vivo assay [D-1-Nal(4)]endomorphin-2
      was also the most potent analogue of the series.

PMID- 16624334
TI  - Persistence and permanence in a metapopulation model with space-limited
      recruitment.
AB  - In this paper we analyze a metapopulation model with space-limited recruitment.
      The model describes the population dynamics of sessile adult and planktonic
      larvae in a common larval pool. We introduce the basic reproduction number of
      each species which is the expected number of future larvae reproduced by one
      larva. We consider the conditions for the persistence of the multi-species and
      multi-habitats model and the permanence of the single-species model.
      Subsequently, we consider the conditions for the existence of the non-trivial
      steady state of the single-species model and its global stability, and the
      permanence of the two species and two habitats model.

PMID- 16624335
TI  - Influence of stochastic perturbation on prey-predator systems.
AB  - We analyse the influence of various stochastic perturbations on prey-predator
      systems. The prey-predator model is described by stochastic versions of a
      deterministic Lotka-Volterra system. We study long-time behaviour of both
      trajectories and distributions of the solutions. We indicate the differences
      between the deterministic and stochastic models.

PMID- 16624336
TI  - Limit cycles in a chemostat model for a single species with age structure.
AB  - We model an age-structured population feeding on an abiotic resource by combining
      the Gurtin-MacCamy [Math. Biosci. 43 (1979) 199] approach with a standard
      chemostat model. Limit cycles arise by Hopf bifurcations at low values of the
      chemostat dilution rate, even for simple maternity functions for which the
      original Gurtin-MacCamy model has no oscillatory solutions. We find the exact
      location in parameter space of the Hopf bifurcations for special cases of our
      model. The onset of cycling is largely independent of both the form of the
      resource uptake function and the shape of the maternity function.

PMID- 16624337
TI  - Extinction times for a birth-death process with two phases.
AB  - Many populations have a negative impact on their habitat or upon other species in
      the environment if their numbers become too large. For this reason they are often
      subjected to some form of control. One common control regime is the reduction
      regime: when the population reaches a certain threshold it is controlled (for
      example culled) until it falls below a lower predefined level. The natural model
      for such a controlled population is a birth-death process with two phases, the
      phase determining which of two distinct sets of birth and death rates governs the
      process. We present formulae for the probability of extinction and the expected
      time to extinction, and discuss several applications.

PMID- 16624338
TI  - Differential responses of pulmonary endothelial phenotypes to cyclical stretch.
AB  - Endothelial phenotypes derived from different pulmonary vascular segments have
      markedly different permeability response to inflammatory agonists, but their
      responses to mechanical strain have not been characterized. Therefore, we
      evaluated the effect of cyclical stretch on cell shape, cell membrane wounding,
      and junctional beta-catenin in rat pulmonary artery (RPAEC) and microvascular
      (RPMVEC) endothelial cell monolayers. After 24 h of 24% uniaxial strain at 40
      cycles/min, RPAEC but not RPMVEC reoriented transverse to the axis of strain.
      Total beta-catenin increased in RPAEC but decreased in RPMVEC. Transient plasma
      membrane wounding was produced by cyclical biaxial strain of 34% or by scratching
      of monolayers with a needle and was indicated by retention of lysine fixable
      fluorescent 70 kDa dextran. Junctional beta-catenin was quantified by
      fluorescence intensity and image analysis. beta-catenin fluorescence was
      significantly lower in wounded cells than in adjacent uninjured cells in both
      phenotypes, and the decrease was significantly greater in RPAEC compared to
      RPMVEC in both scratched (57% vs. 30%) and stretched (55% vs. 37%) cells. Using
      immunoprecipitation, VE-cadherin-associated beta-catenin decreased significantly
      in RPAEC (61%) but E-cadherin-associated beta-catenin was not significantly
      decreased in RPMVEC after 34% biaxial cyclical strain. These data suggest that
      RPAEC more readily remodel cell-cell adhesions during cyclical stretch than
      RPMVEC and that a reduced intercellular adhesion adjacent to wounded cells could
      serve as transvascular leak sites in both phenotypes.

PMID- 16624339
TI  - Enhanced proangiogenic signaling in thrombospondin-1-deficient retinal
      endothelial cells.
AB  - Thrombospondin-1 (TSP1) is an endogenous inhibitor of angiogenesis, which limits
      blood vessel density in normal tissues and curtails tumor growth. Previous
      studies of the molecular and cellular effects of TSP1 in angiogenesis have been
      contradictory. Here, we show that retinal endothelial cells (REC) prepared from
      TSP1-deficient (TSP1-/-) mice are more proliferative and migratory compared to
      the wild type REC. We observed up-regulation of the cell cycle regulators,
      including cyclin A, D1, and Cdk2, as well as the enhanced sequential activities
      of Src, PI3-kinase, Akt/PKB, Rac1/Cdc42 GTPases, and p38 MAP kinase in TSP1-/-
      REC. The increased levels of fibronectin and active Akt/PKB were also observed in
      retinal vasculature of TSP1-/- mice in vivo. Inhibition of Src/PI3-kinase/P38 MAP
      kinase activities in TSP1-/- REC resulted in decreased migration. Furthermore,
      TSP1-/- REC showed decreased intracellular levels of active Fyn and JNK2 without
      affecting caspase-3 activity. Thus, our results demonstrate that in the absence
      of TSP1, the proangiogenic signaling is enhanced, possibly through up-regulation
      of fibronectin expression. The enhanced signaling further promotes EC
      proliferation, migration, and survival. These novel observations support the
      TSP1's role as an endogenous inhibitor of angiogenesis whose endothelium
      expression promotes a quiescent, differentiated phenotype.

PMID- 16624340
TI  - Pigment-epithelium-derived factor (PEDF) inhibits angiotensin-II-induced vascular
      endothelial growth factor (VEGF) expression in MOLT-3 T cells through anti
      oxidative properties.
AB  - Angiotensin II (Ang II), the dominant effector of the renin-angiotensin system,
      elicits numerous inflammatory-proliferative responses, thereby being involved in
      angiogenesis. T cells play an important role in angiogenesis as well by
      delivering vascular endothelial growth factor (VEGF) to inflammatory sites. Since
      we have previously shown that pigment-epithelium-derived factor (PEDF) blocks the
      Ang II signaling in endothelial cells, we studied here whether PEDF could inhibit
      the Ang-II-induced VEGF expression in MOLT-3 T and examined the potential
      mechanism of PEDF inhibitory effects. Ang II significantly up-regulated VEGF mRNA
      levels in MOLT-3 T cells, which was inhibited by PEDF or olmesartan, an Ang II
      type 1 receptor blocker. PEDF blocked the Ang-II-induced reactive oxygen species
      (ROS) generation in MOLT-3 T cells. Furthermore, H(2)O(2) was found to up
      regulate VEGF mRNA levels in MOLT-3 T cells in a dose-dependent manner. These
      results demonstrate that PEDF could inhibit the Ang-II-induced VEGF expression in
      MOLT-3 T cells via suppression of ROS generation. Blockade by PEDF of VEGF
      expression in T cells may become a novel therapeutic target for pathological
      angiogenesis.

PMID- 16624341
TI  - Pericytes from human non-small cell lung carcinomas: an attractive target for
      anti-angiogenic therapy.
AB  - Anti-angiogenic strategies have largely focused on endothelial cells and
      progenitors. However, pericytes are also an important component of vasculature.
      Perivascular cells from normal tissues have been widely reported, yet have not
      been extensively studied from human tumors. We have investigated pericytes from
      tumors of patients with lung cancer, the leader of cancer-related deaths in both
      men and women. Antibodies and magnetic beads were used to isolate cells from non
      small cell lung carcinomas (NSCLC). The morphology of the pericytes was distinct
      with multiple elongated cytoplasmic extensions. Molecular expression of
      angiogenic genes was quantified by RT-PCR. Flow cytometric analysis shows that
      NSCLC pericytes express antigens such NG2 and VEGFR1 and present the ganglioside
      3G5. The value of pericytes as models of tumor vasculature was demonstrated in
      cell-culture-based angiogenesis assays such as tube formation and proliferation.
      Results show that pericytes from some NSCLC but not all were able to maintain
      tubes networks on Matrigel. Pericyte function can be influenced by angiogenic
      growth factors or anti-angiogenic agents. Pericytes displayed invasive action
      against NSCLC clusters in the absence of other cell types. Perivascular cells
      contribute to the progression of disease and are an attractive target for anti
      angiogenic therapy.

PMID- 16624342
TI  - Measurement of RBC deformation and velocity in capillaries in vivo.
AB  - Red blood cells (RBC) become deformed while flowing through capillaries. We
      captured images of blood flow in capillaries and of RBC in the rat mesentery
      using a high-speed camera at 2000 frames/s and then directly measured and
      estimated the deformation and velocity of RBC in a non-uniform capillary. The
      distribution of the capillary diameter was determined by image processing. We
      applied a deformation index and simple modeling to observe RBC deformation in
      capillaries. The average capillary diameter was approximately 6.2 microm, and the
      average velocity of RBC was about 1.85 mm/s. The average deformation index of RBC
      in the capillary was about 1.55. The present results showed that RBC in
      capillaries generally assume a specific shape depending on external forces such
      as the velocity of the blood flow and capillary diameter in vivo.

PMID- 16624343
TI  - Motion-defined form processing in extremely premature children.
AB  - Children born extremely prematurely are at risk for a variety of problems with
      motion analysis, including problems with motion-defined (MD) form recognition
      [Downie, A. L. S., Jakobson, L. S., Frisk, V., & Ushycky, I. (2003).
      Periventricular brain injury, visual motion processing, and reading and spelling
      abilities in children who were extremely-low-birthweight. Journal of the
      International Neuropsychological Society, 9, 440-449]. The aims of the present
      study were (1) to examine the impact of retinopathy of prematurity (ROP) and mild
      periventricular brain injury (PVBI) on MD form processing in this population; (2)
      to assess relationships between MD form recognition in these children and their
      performance in several other areas of visual competence. To this end, a battery
      of visual and visuomotor tests was administered to 43, 5- and 6-year old,
      extremely premature children, all of whom had escaped severe PVBI. A group of
      full-term controls was also studied. Relative to controls, premature children
      displayed clear deficits in MD form recognition and these deficits were related
      to the presence of ROP and/or mild PVBI, rather than to a history of prematurity
      per se. Regression analyses revealed significant associations in premature
      children between MD form processing deficits and problems with visual search,
      stereopsis, visuoconstructive and graphomotor skills, motor development, and
      Performance IQ. The results suggest that assessment of sensitivity to MD forms
      may be useful in the early identification of preterm children at greatest risk
      for visual problems associated with dorsal stream dysfunction.

PMID- 16624344
TI  - Photic entrainment and masking of prosimian circadian rhythms (Otolemur
      garnettii, Primates).
AB  - Besides rods the retina of the nocturnal greater bushbaby, genus Otolemur, also
      contains small cones which, however, do not allow color vision. In order to find
      out whether these cones might be involved in circadian photoreception in the
      Garnet's galago Otolemur garnettii we determined the threshold for photic
      entrainment. Activity recordings revealed a short circadian period of 22.6+/-0.7
      h subjected to pronounced long-lasting aftereffects. The animals had a relatively
      high threshold for photic entrainment at about 3-30 lux. This indicates that the
      cones and/or other, as yet unidentified photoreceptive retinal cells may be
      involved in circadian photoreception. The galagos' threshold for photic
      entrainment also depended on the luminosity during the dark phase of the light
      dark cycles. Results furthermore showed that in Otolemur aftereffects may play a
      crucial role for circadian entrainment. Light time luminosities just below the
      individuals' threshold for photic entrainment strongly inhibited the galagos'
      locomotor activity and, thus, produced pronounced negative masking effects on
      their free-running circadian activity rhythm. From this it may be inferred that
      masking direct effects of light are not induced or mediated via the circadian
      system, i.e. via the circadian pacemaker in the hypothalamic suprachiasmatic
      nuclei, but at a higher central nervous integrational stage.

PMID- 16624345
TI  - A telemetric examination of cardiovascular function during the development of,
      and recovery from, opiate dependence in rats.
AB  - Rats were subject to daily injections of morphine or saline and were then allowed
      to spontaneously withdraw from morphine for 4 days. Mean arterial blood pressure
      (MAP) and heart rate (HR) were recorded continuously, via radiotelemetry, during
      the development of, and recovery from, opiate dependence. Injections of morphine
      produced pronounced and prolonged increases in MAP and HR which increased as
      morphine dose increased. There were also significant increases in MAP during the
      19-23 h period after each morphine injection indicating the presence of
      withdrawal. Spontaneous withdrawal from morphine was associated with a pronounced
      (20% increase from baseline) and prolonged (72 h) increase in MAP. MAP returned
      to baseline levels 72-96 h after last morphine exposure. These results show that
      intermittent injections of morphine, and spontaneous withdrawal from these
      injections, are associated with profound alterations in cardiovascular function
      and confirm the usefulness of radiotelemetry for studying opiate dependence.

PMID- 16624346
TI  - Stress-induced muscle and cutaneous hyperalgesia: differential effect of
      milnacipran.
AB  - We previously demonstrated that repeated swim stress produces long-term cutaneous
      hyperalgesia in rats. We have now determined the effect of stress upon muscle
      nociception and the anti-nociceptive efficacy of the norepinephrine-serotonin
      reuptake inhibitor, milnacipran (MIL) in this model. Rats were subjected to
      either 10-20 min daily sessions of forced swimming (FS) for 3 days, or sham
      swimming (SS) or control (CT). Maximal forelimb grip strength and hot plate
      response latencies were estimated before and after the conditioning to assess
      muscle and thermal nociception, respectively. MIL (1-30 mg/kg/i.p.) or vehicle
      was started 7 days before the conditioning protocol. There were significant
      reductions in maximal grip strength and hot plate latencies only in FS/vehicle
      rats. Subsequent carrageenan administration (2 mg/75 microl each triceps)
      diminished grip strength in all groups 24 h later, with grip strength lower in
      FS/vehicle and SS/vehicle rats than in CT/vehicle rats. Treatment with MIL before
      the stress prevented the reduction in grip strength in all groups but it was
      ineffective in preventing FS-induced reductions in hot plate response latencies.
      Thus, repeated stress produces muscle hyperalgesia that can be pharmacologically
      dissociated from cutaneous hyperalgesia, suggesting that different mechanisms may
      underlie these two phenomena.

PMID- 16624347
TI  - Lasting anxiogenic effects of feline predator stress in mice: sex differences in
      vulnerability to stress and predicting severity of anxiogenic response from the
      stress experience.
AB  - Previous work in male Swiss Webster (CFW) mice demonstrated a long lasting effect
      of predator stress on risk assessment in the elevated plus maze (EPM). Most
      severe effects (increases in risk assessment) were seen following a brief
      unprotected exposure to a cat. Lesser effects were produced by a brief exposure
      of mice to the cat exposure room without a cat in the room (room stress). This
      graded response is analogous to the covariation of symptom severity and severity
      of the precipitating stressor in posttraumatic stress disorder (PTSD). The
      present study extended these findings to another strain of mice, C57/BL6, and a
      broader range of tests of anxiety-like behavior, including EPM, acoustic startle
      response and light/dark box test. Sex was introduced as a variable to investigate
      if females might be more susceptible to the effects of stressors than males, as
      has been suggested in human PTSD. Graded and lasting (7 days) effects of a 10 min
      exposure to a cat (predator stress) or to the cat exposure room only (room
      stress) were observed on lighted chamber avoidance in the light/dark box. Room
      stress was without effect on startle responses, but predator stress enhanced peak
      startle amplitudes measured in the light or in the dark. There was no evidence of
      light-enhancement of startle in C57 mice. Female mice were more susceptible to
      the effects of predator and room stress, depending on the measure. Females only
      responded to cat exposure with a lasting increase in average startle amplitude.
      This was due to an increased and more prolonged multipeak response to startle
      after the first and maximal peak startle response. In addition, in females, room
      and predator stress were equally anxiogenic in measures of open arm avoidance in
      the EPM. In contrast, room stress was without effect on open arm avoidance in
      males, but cat exposure was as anxiogenic in males as it was in females. These
      findings suggest EPM anxiety in females is affected more by the milder stress of
      room exposure. Severity of effects of predator stress on anxiety-like behaviors
      in EPM and startle were well predicted (60% of the variance) by measures of cat
      behavior and probability of mouse defensive response to particular cat behaviors
      during the cat exposure. Finally, factor analysis indicated that different tests
      of anxiety-like behavior may be measuring different and independent aspects of
      mouse affect. Moreover, stressors had no lasting effects on sugar solution
      consumption. Implications of these findings for modeling PTSD and using
      transgenic strains of mice to study lasting effects of stress on affect are
      discussed.

PMID- 16624348
TI  - Sweet and fat taste preference in obesity have different associations with
      personality and eating behavior.
AB  - The aim of this study was to test associations between self-reported attitudes of
      sweet and fat taste preferences and psychological constructs of eating behavior
      and personality in obesity. Sixty obese patients were included. The Three Factor
      Eating Questionnaire was used for the assessment of psychological constructs of
      eating behavior, and the Swedish universities Scales of Personality was used for
      measuring personality traits. A strong sweet taste preference was associated with
      more neurotic personality traits (P=.003), in particular lack of assertiveness
      (P=.001) and embitterment (P=.002). Strong fat taste preference was rather
      related to lower levels of the eating characteristic cognitive restraint
      (P=.017), implying less attempts to restrict and control food intake. Whereas
      strong sweet taste preference was linked to a personality style in obesity,
      strong fat preference could be more an aspect of eating behavior. A
      psychobiological stress model is discussed in relation to the results on sweet
      preference and hampered personality functioning.

PMID- 16624349
TI  - Familiarization and cross-familiarization of wheel running and LiCl in
      conditioned taste aversion.
AB  - Familiarization with an unconditioned stimulus (US) interferes with the learning
      of subsequent Pavlovian conditioned associations. We conducted a series of
      experiments exploiting this US preexposure effect to elucidate the underlying
      mechanism of conditioned taste aversion in rats induced by voluntary wheel
      running. Experiment 1 demonstrated that running-induced taste aversion was
      alleviated if rats had sufficient experience of running in advance. In
      Experiments 2A and 2B, preexposure to wheel running had no effect on subsequent
      taste aversion conditioning by lithium chloride (LiCl) injection. In Experiment
      3, however, we observed a weak partial interference from the LiCl injection
      pretreatment to the subsequent conditioning by wheel running US. This US
      crossover effect suggests the possibility that wheel running and LiCl injection
      share a common or similar physiological mechanism in inducing taste aversion.

PMID- 16624350
TI  - The enzymic and chemically induced decomposition of glucosinolates.
AB  - While the myrosinase-glucosinolate system has been reviewed in recent years by a
      number of authors, little attention has been paid to the enzymic and non-enzymic
      degradation of glucosinolates. Non-enzymic degradation processes are particularly
      important in the processing of brassica vegetables with respect to both flavour
      and in the role of glucosinolates as precursors of anticancer compounds in the
      diet. This review highlights early empirical work on glucosinolate degradation
      along with more recent aspects related to current research on mechanism of
      glucosinolate degradation in plants, microbes and animals.

PMID- 16624351
TI  - Acylated 5,7,2',6'-oxygenated flavone glycosides from Andrographis alata.
AB  - Five acylated 5,7,2',6'-oxygenated flavone glycosides along with the known
      5,2',6'-trihydroxy-7-methoxyflavone-2'-O-beta-d-glucopyranoside have been
      isolated from the whole plant of Andrographis alata. The structures of the
      compounds were established from spectral (mainly 1D and 2D NMR) and chemical
      studies.

PMID- 16624352
TI  - Crotalic and emarginellic acids: two triterpenes from Crotalaria emarginella and
      anti-inflammatory and anti-hepatotoxic activity of crotalic acid.
AB  - The aerial parts of Crotalaria emarginella Vatke (Leguminosae) has afforded two
      triterpenes, characterized as 3alpha-hydroxy-arbor-12-ene-28-carboxylic acid,
      designated as crotalic acid (1), and 2beta,3beta,21-trihydroxy-arbor-12-ene-29
      carboxylic acid, designated as emarginellic acid (2). The structures of the
      isolated products were elucidated on the basis of spectral and chemical studies.
      On screening the biological activity, the crotalic acid (1) exhibited a
      significant anti-inflammatory activity (dose: 10mg/kg), which showed 53%
      inhibitory effect. Whereas, the standard oxyphenyl butazone (100mg/kg) exhibited
      69% inhibition with respect to carrageenan (0.05ml, 1%) used to cause
      inflammation in rat paw method. In addition, it also showed anti-hepatotoxic
      activity by 13-30% with respect to standard silybon-70 (35-57%) against CCl(4)
      induced toxicity in Wistar rats.

PMID- 16624353
TI  - Antioxidant activity of prenylated hydroquinone and benzoic acid derivatives from
      Piper crassinervium Kunth.
AB  - Growing evidence suggests that RNOS (reactive nitrogen and oxygen species) are
      involved in the damage of biomolecules, contributing to the aetiology of several
      human diseases. Thus, the demand for antioxidants has stimulated the search for
      new compounds with potential use in this field. The in vitro antioxidant
      potential of prenylated hydroquinones and prenylated 4-hydroxy-benzoic acids from
      fruits of P. crassinervium was evaluated in terms of their capacity to suppress
      both DPPH (2,2-diphenyl-1-picrylhydrazyl) radical and chemiluminescence produced
      from luminol, using 2,2'-azo-bis(2-amidinopropane) (ABAP) as a peroxyl radical
      source. The inhibition of lipid peroxidation was assessed using liposomes from
      phosphatidylcholine as a membrane model. The prenylated hydroquinones had higher
      antioxidant activity than the benzoic acids and, among the hydroquinones, the E
      isomer was more efficient than the Z isomer.

PMID- 16624354
TI  - Caffeine biosynthesis and adenine metabolism in transgenic Coffea canephora
      plants with reduced expression of N-methyltransferase genes.
AB  - In anti-sense and RNA interference transgenic plants of Coffea canephora in which
      the expression of CaMXMT1 was suppressed, caffeine biosynthesis from [8
      (14)C]adenine was investigated, together with the overall metabolism of [8
      (14)C]adenine. Compared with wild type control plants, total purine alkaloid
      biosynthesis from adenine and conversion of theobromine to caffeine were both
      reduced in the transgenic plants. As found previously, [8-(14)C]adenine was
      metabolised to salvage products (nucleotides and RNA), to degradation products
      (ureides and CO(2)) and to purine alkaloids (theobromine and caffeine). In the
      transgenic plants, metabolism of [8-(14)C]adenine shifted from purine alkaloid
      synthesis to purine catabolism or salvage for nucleotides. HPLC analysis revealed
      a significantly reduced caffeine content in the transgenic plants. A small
      quantity (less than 20 nmol g(-1) fresh weight) of xanthosine had accumulated in
      at least one of the transgenic plants.

PMID- 16624355
TI  - The leukemia inhibitory factor receptor gene is not involved in the etiology of
      pituitary dwarfism in German shepherd dogs.
AB  - Pituitary dwarfism in German shepherd dogs is characterized by combined pituitary
      hormone deficiency (CPHD) and intrapituitary cyst formation. Activation of the
      leukemia inhibitory factor (LIF)-LIF receptor (LIFR) signal transduction pathway
      results in a similar phenotype in (transgenic) mice. We therefore assessed the
      role of the LIFR in the etiology of pituitary dwarfism in German shepherd dogs. A
      polymorphic microsatellite marker (UULIFR) was used to analyze the segregation of
      the LIFR gene in 22 German shepherd dogs from 4 pedigrees, each including one
      dwarf. There was no allelic association between UULIFR and the dwarfism
      phenotype. Based on our findings LIFR was excluded as a candidate gene for CPHD.

PMID- 16624356
TI  - Danofloxacin (Advocin) reduces the spread of contagious bovine pleuropneumonia to
      healthy in-contact cattle.
AB  - Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp.
      mycoides SC (MmmSC), is one of the most important diseases of cattle in Sub
      Saharan Africa. The live T1/44 vaccine is normally used for its control but
      produces only transient protection and gives rise to adverse reactions. The
      present study evaluated the efficacy of danofloxacin (2.5% Advocintrade mark,
      Pfizer Ltd.) for the treatment of naturally infected cattle and in the prevention
      of CBPP transmission to in-contact cattle. Adult cattle, taken from a natural
      outbreak, were placed into two groups of 10 animals and kept on a research farm
      in paddocks 50m apart. One group was treated with 2.5mg/kg danofloxacin on days
      0, 1 and 2; the other group were saline treated. On day 2, 10 CBPP-free,
      seronegative cattle were placed in contact with each of the two groups. All
      cattle were monitored for 3.5 months. No differences were seen in clinical
      improvement of the CBPP-affected cattle treated with danofloxacin compared with
      the untreated CBPP-affected cattle with approximately half of each group being
      withdrawn because of CBPP or showing CBPP lesions at post mortem examination.
      Clinical scores of the two groups were also similar. However cattle kept in
      contact with the danofloxacin-treated CBPP-affected animals showed significantly
      fewer lesions, less mortality and fewer animals were seropositive (P<0.02) and
      had reduced clinical scores (P<0.001) compared to cattle kept in contact with
      untreated CBPP-affected cattle. MmmSC was also isolated from fewer contact
      controls kept with the treated group. These findings could have important
      implications for the control of CBPP in Africa.

PMID- 16624357
TI  - Effect of supplementation of Agaricus mushroom meal extracts on enzyme activities
      in peripheral leukocytes of calves.
AB  - To investigate the effect of Agaricus mushroom meal on the energy metabolism in
      animal tissues; plasma glucose, triglyceride, cholesterol and immunoreactive
      insulin (IRI) concentrations and activities of enzymes related to energy
      metabolism in plasma and peripheral leukocytes were measured in Japanese Black
      WagyuxHolstein F1 calves supplemented with Agaricus blazei Murill (A. blazei)
      extract in milk-replacer at the dose of 60g/head/day for 4 weeks. Activities of
      malate dehydrogenase and aspartate aminotransferase in cytosol and glutamate
      dehydrogenase in mitochondria, and the malate dehydrogenase/lactate dehydrogenase
      ratio in cytosol in peripheral leukocytes of calves with A. blazei were
      significantly higher than those in control calves without A. blazei. It was
      concluded that supplementation of Agaricus mushroom meal extract was effective in
      activation of enzymes related to energy metabolism in peripheral leukocytes of
      calves.

PMID- 16624359
TI  - Liver disease in young rabbits infected by calicivirus through nasal and oral
      routes.
AB  - Calicivirus infection causes rabbit haemorrhagic disease (RHD) that kills more
      than 90% of adult animals, whereas young rabbits are naturally resistant to this
      viral disease. It has been proposed that the different response of adult and
      young rabbits to calicivirus infection is due to absence of viral receptors in
      respiratory and digestive systems of young animals. We have searched for liver
      disease in 4-week-old rabbits inoculated with a calicivirus suspension by
      intranasal and oral routes. These young rabbits showed cell damage and
      mononuclear infiltration of the liver. The hepatic lesions were associated with
      mild to moderate increase in circulating transaminases. We conclude that the
      previously reported reduction of viral receptors in the epithelium of respiratory
      and digestive systems of young rabbits does not inhibit calicivirus from inducing
      liver disease in these hosts.

PMID- 16624358
TI  - Invasive potential of bacterial isolates associated with subclinical bovine
      mastitis.
AB  - This work describes differences in the invasive ability of bacterial isolates
      associated with mastitis. Invasion ability was determined by the uptake and
      survival in a primary culture of bovine mammary epithelial cells (BMEC). BMEC
      were isolated from a healthy lactating cow and characterized by their morphology,
      immunostaining for cytokeratin and the detection of beta- and kappa-casein mRNAs.
      Ten bacterial isolates comprising the staphylococcal species Staphylococcus
      aureus (3), Staphylococcus epidermidis (1), Staphylococcus haemolyticus (1),
      Staphylococcus equorum (2), Staphylococcus xylosus (1) and Brevibacterium
      stationis (2) obtained from raw milk of cows with mastitis from backyard farms
      were assayed for their ability to invade BMEC. Only two S. aureus and one S.
      epidermidis isolates were able to invade BMEC, at similar levels to the S. aureus
      control strain ATCC 27543. In conclusion, using the in vitro model of infection
      used in this study, differences in bacterial invasion capability may be detected.

PMID- 16624361
TI  - Ultrastructure of the water-clear cell in the parathyroid gland of SAMP6 mice.
AB  - Although the parathyroid water-clear cell is very rare, it has clinical
      significance because of its association with parathyroid hyperplasia or adenoma.
      SAMP6, a substrain of senescence-accelerated mouse, was developed as an animal
      model for senile osteoporosis. We investigated the morphology of the parathyroid
      glands in SAMP6 and age-matched normal mouse SAMR1. The parathyroid water-clear
      cells, which contained numerous vacuoles and the crystalloid inclusions, were
      found in SAMP6 mice at 5, 8 and 12 months of age. It was noted that the number of
      water-clear cells increased with aging, which are fairly consistent with the
      change of the serum parathyroid hormone (PTH) level. We did not find any water
      clear cells in the parathyroid glands of SAMR1 mice. The existence of water-clear
      cells may represent hyperfunction of the parathyroid glands in SAMP6.

PMID- 16624360
TI  - Enhancement of enrofloxacin serum antibacterial activity by calcium primed
      broilers.
AB  - The aim of this trial was to assess the effect that calcium gluconate priming of
      468 broilers has on the antibacterial activity of a standard dose of
      enrofloxacin. Hence, a series of oral pharmacokinetic studies were carried out in
      four groups of broilers medicated individually through an oral cannula as
      follows: group A, medicated only with enrofloxacin 10mg/kg; group B, receiving
      immediately one after the other, calcium gluconate (200mg/kg) and enrofloxacin
      10mg/kg; group C, dosed first with calcium gluconate (200mg/kg) and 1h later
      enrofloxacin (10mg/kg); and group D, dosed first with calcium gluconate
      (200mg/kg) and 2h later enrofloxacin (10mg/kg). Broilers were bled at different
      times after the dose of enrofloxacin and antibacterial activity, measured as
      concentration of enrofloxacin, was measured by an agar diffusion assay. Results
      revealed that group D the greatest values of maximum serum concentration
      (Cs(max)), area under the concentration vs. time curve (AUC) and area under the
      moment curve (AUMC). These values were statistically higher than the
      corresponding ones derived from groups A, B and C (P<0.05). Taking Cs(max) and
      AUC values of group A as reference baseline, an increase of 24% and 50%,
      respectively, was obtained in group D. Group B had the lowest Cs(max), AUC, AUMC
      and elimination half life (T(1/2)beta) and these values were statistically
      different from groups A, C and D (P<0.05). The T(1/2)beta was statistically
      longer in groups C and D as compared with A and B, and the former groups were
      also different between each other (P<0.05). These results show that if calcium
      gluconate is first dosed to broilers and 2h later enrofloxacin is administered
      (as in group D), a more pronounced antibacterial activity of enrofloxacin can be
      obtained. A challenge of this sequential dosing scheme in a field trial may
      reveal its clinical value.

PMID- 16624362
TI  - Repression of HPV16 early region transcription by the E2 protein.
AB  - HPV16 DNA is often integrated in cancers, disrupting the E1 or E2 genes. E2 can
      repress the E6/E7 promoter, but other models have been proposed to explain why
      integration promotes malignant progression. E1 and E2 are required for viral
      replication, and so genetic analysis of their role in transcriptional regulation
      is complex. Therefore, we developed an extrachromosomal vector containing HPV16
      to undertake a genetic analysis of the E1 and E2 genes. We demonstrate that the
      E2 protein is primarily a transcriptional repressor when expressed from the
      virus. Furthermore, repression requires both the transactivation function of E2
      and specific binding of E2 to the LCR. We find no evidence that the E1 protein
      directly modulates HPV16 gene expression. However, certain E1 mutations modulated
      transcription indirectly by altering splicing of E2 mRNA species. These data
      provide important insight into which E1 and E2 functions are optimal targets for
      anti-viral therapies.

PMID- 16624363
TI  - Saturation of TRIM5 alpha-mediated restriction of HIV-1 infection depends on the
      stability of the incoming viral capsid.
AB  - HIV-1 infection is restricted at a post-entry stage in some simian cell lines by
      species-specific variants of TRIM5 alpha. Restriction targets the viral capsid
      protein (CA) and results in attenuated reverse transcription. TRIM5 alpha
      restriction can be inhibited by the addition of noninfectious virus-like
      particles (VLPs), thus rendering cells permissive for infection by an HIV-1
      reporter virus. Through the use of HIV-1 VLPs containing Gag cleavage site
      substitutions and point mutations in CA which alter the stability of the viral
      capsid, we demonstrate that saturation of TRIM5 alpha restriction depends on the
      stability of the capsid in the incoming VLPs. Differences in the requirement for
      cleavage of the specific sites in Gag were observed between distinct African
      green monkey cell lines. The results strongly suggest that the mechanism of HIV-1
      restriction by TRIM5 alpha involves engagement of the viral capsid by the
      restriction factor prior to completion of uncoating.

PMID- 16624364
TI  - DNA vaccines expressing the duck hepatitis B virus surface proteins lead to
      reduced numbers of infected hepatocytes and protect ducks against the development
      of chronic infection in a virus dose-dependent manner.
AB  - We tested the efficacy of DNA vaccines expressing the duck hepatitis B virus
      (DHBV) pre-surface (pre-S/S) and surface (S) proteins in modifying the outcome of
      infection in 14-day-old ducks. In two experiments, Pekin Aylesbury ducks were
      vaccinated on days 4 and 14 of age with plasmid DNA vaccines expressing either
      the DHBV pre-S/S or S proteins, or the control plasmid vector, pcDNA1.1Amp. All
      ducks were then challenged intravenously on day 14 of age with 5 x 10(7) or 5 x
      10(8) DHBV genomes. Levels of initial DHBV infection were assessed using liver
      biopsy tissue collected at day 4 post-challenge (p.c.) followed and immunostained
      for DHBV surface antigen to determine the percentage of infected hepatocytes. All
      vector vaccinated ducks challenged with 5 x 10(7) and 5 x 10(8) DHBV genomes had
      an average of 3.21% and 20.1% of DHBV-positive hepatocytes respectively at day 4
      p.c. and 16 out of 16 ducks developed chronic DHBV infection. In contrast, pre
      S/S and S vaccinated ducks challenged with 5 x 10(7) DHBV genomes had reduced
      levels of initial infection with an average of 1.38% and 1.93% of DHBV-positive
      hepatocytes at day 4 p.c. respectively and 10 of 18 ducks were protected against
      chronic infection. The pre-S/S and the S DNA vaccinated ducks challenged with 5 x
      10(8) DHBV genomes had an average of 31.5% and 9.2% of DHBV-positive hepatocytes
      on day 4 p.c. respectively and only 4 of the 18 vaccinated ducks were protected
      against chronic infection. There was no statistically significant difference in
      the efficacy of the DHBV pre-S/S or S DNA vaccines. In conclusion, vaccination of
      young ducks with DNA vaccines expressing the DHBV pre-S/S and S proteins induced
      rapid immune responses that reduced the extent of initial DHBV infection in the
      liver and prevented the development of chronic infection in a virus dose
      dependent manner.

PMID- 16624365
TI  - Differential distribution of non-structural proteins of foot-and-mouth disease
      virus in BHK-21 cells.
AB  - Differences in the kinetics of expression and cell distribution among FMDV non
      structural proteins (NSPs) have been observed in BHK-21-infected cells. 3D(pol)
      was the first protein detected by immunofluorescence (1.5 h p.i.), showing a
      perinuclear distribution. At 2-2.5 h p.i., 2B, 2C, 3B and 3C were detected,
      mostly exhibiting a punctuated, scattered pattern, while 3A and 3D(pol) appeared
      concentrated at one side of the nucleus. This distribution was exhibited by all
      the NSPs from 3 h p.i., being 2C and, to a lesser extent, precursors 2BC and
      3ABBB, the only proteins detected by Western blotting at that infection time.
      From 4 h p.i., all mature NSPs as well as precursors 2BC, 3ABBB, 3ABB, 3AB and
      3CD(pol) were detected by this technique. In spite of their similar
      immunofluorescence patterns, 2C and 3A co-localized partially by confocal
      microscopy at 3.5 h p.i., and 3A, but not 2C, co-localized with the ER marker
      calreticulin, suggesting differences in the distribution of these proteins and/or
      their precursors as infection proceeded. Transient expression of 2C and 3AB
      resulted in punctuated fluorescence patterns similar to those found in early
      infected cells, while 3A showed a more diffuse distribution. A shift towards a
      fibrous pattern was noticed for 3ABB, while a major change was observed in cells
      expressing 3ABBB, which displayed a perinuclear fibrous distribution.
      Interestingly, when co-expressed with 3D(pol), the pattern observed for 3ABBB
      fluorescence was altered, resembling that exhibited by cells transfected with
      3AB. Transient expression of 3D(pol) showed a homogeneous cell distribution that
      included, as determined by confocal microscopy, the nucleus. This was confirmed
      by the detection of 3D(pol) in nuclear fractions of transfected cells. 3D(pol)
      and its precursor 3CD(pol) were also detected in nuclear fractions of infected
      cells, suggesting that these proteins can directly interact with the nucleus
      during FMDV infection.

PMID- 16624367
TI  - Influenza virus inhibits RNA polymerase II elongation.
AB  - The influenza virus RNA-dependent RNA polymerase interacts with the serine-5
      phosphorylated carboxy-terminal domain (CTD) of the large subunit of RNA
      polymerase II (Pol II). It was proposed that this interaction allows the viral
      RNA polymerase to gain access to host mRNA-derived capped RNA fragments required
      as primers for the initiation of viral mRNA synthesis. Here, we show, using a
      chromatin immunoprecipitation (ChIP) analysis, that similar amounts of Pol II
      associate with Pol II promoter DNAs in influenza virus-infected and mock-infected
      cells. However, there is a statistically significant reduction in Pol II
      densities in the coding region of Pol II genes in infected cells. Thus, influenza
      virus specifically interferes with Pol II elongation, but not Pol II initiation.
      We propose that influenza virus RNA polymerase, by binding to the CTD of
      initiating Pol II and subsequent cleavage of the capped 5' end of the nascent
      transcript, triggers premature Pol II termination.

PMID- 16624366
TI  - A single amino acid substitution in the central portion of the West Nile virus
      NS4B protein confers a highly attenuated phenotype in mice.
AB  - West Nile virus (WNV) NS4B is a small hydrophobic nonstructural protein that is
      hypothesized to participate both in viral replication and evasion of host innate
      immune defenses. The protein has four cysteine residues (residues 102, 120, 227,
      and 237). Since cysteines are often critical for the function of proteins, each
      of the four cysteine residues found in WNV NS4B was mutated to serine by site
      directed mutagenesis. While three of these substitutions had little effect on
      replication or mouse virulence phenotypes, the C102S mutation was associated with
      a temperature-sensitive phenotype at 41 degrees C as well as attenuation of the
      neuroinvasive and neurovirulence phenotypes in mice.

PMID- 16624368
TI  - Measurement of the initial phase of ozone decomposition in water and wastewater
      by means of a continuous quench-flow system: application to disinfection and
      pharmaceutical oxidation.
AB  - Due to a lack of adequate experimental techniques, the kinetics of the first 20s
      of ozone decomposition in natural water and wastewater is still poorly
      understood. Introducing a continuous quench-flow system (CQFS), measurements
      starting 350 ms after ozone addition are presented for the first time. Very high
      HO. to O3 exposures ratios (Rct=integralHO.dt/integralO3dt) reveal that the first
      20s of ozonation present oxidation conditions that are similar to ozone-based
      advanced oxidation processes (AOP). The oxidation of carbamazepine could be
      accurately modeled using O3 and HO. exposures measured with CQFS during
      wastewater ozonation. These results demonstrate the applicability of bench scale
      determined second-order rate constants for wastewater ozonation. Important
      degrees of pharmaceutical oxidation and microbial inactivation are predicted,
      indicating that a significant oxidation potential is available during wastewater
      ozonation, even when ozone is entirely decomposed in the first 20s.

PMID- 16624369
TI  - Long-term storage conditions for carriers with denitrifying biomass of the
      fluidized, methanol-fed denitrification reactor of the Montreal Biodome, and the
      impact on denitrifying activity and bacterial population.
AB  - The Montreal Biodome has a denitrification system to stabilize the nitrate
      concentration in its 3 million liter seawater aquarium. However, this microbial
      process has failed periodically due to various technical problems. The system can
      take several weeks to recover its full denitrification capacity. In order to
      provide the denitrification system with a backup of active biomass, different
      freezing conditions for the denitrifying biomass were tested. The biomass was
      conserved for 1 week-17 months at -20 degrees C with and without glycerol or at 
      80 degrees C with and without glycerol, and the denitrifying activity was tested
      in batch culture for 140 h periods at various intervals. Our results showed that
      glycerol was required for fast recovery of the microbial community's denitrifying
      activity. The -20 degrees C and -80 degrees C conservation temperatures with
      glycerol gave similar results although there was a short period of nitrite
      accumulation in the -20 degrees C sample. There were no substantial changes in
      the microbial community of any of the frozen samples after 17 months of
      conservation as monitored by denaturing gradient gel electrophoresis. This is the
      first report on the long-term conservation of a complex denitrifying population
      by freezing.

PMID- 16624370
TI  - Kinetics of aniline degradation by Fenton and electro-Fenton processes.
AB  - Aniline degradation at pH 2 by Fenton and electro-Fenton processes was
      kinetically investigated in this study. Electro-Fenton process was found to be
      superior to ordinary Fenton process with the current impacts of 1.2 to 3.1 for
      removal efficiency and 1.2 to 5.8 for degradation rate depending on initial Fe2+
      concentration. This is mainly due to the rapid electrochemical regeneration of
      Fe2+. Overall rate equations for aniline degradation by Fenton and electro-Fenton
      processes (in units of molar and minute) are: [EQUATION: SEE TEXT]. With current
      application, aniline degradation rate seems to be autonomous from Fenton's
      reagent concentrations and approaching a half order with respect to aniline. In
      addition, for complete removal of 0.01 M aniline, the delay in current supply at
      the initial stage could save up to one-third of the total energy required by the
      ordinary electro-Fenton process. As a result, significant reduction in energy
      consumption and operating cost could be obtained by the current-delay operating
      mode.

PMID- 16624371
TI  - Expression of heat shock protein and hemoglobin genes in Chironomus tentans
      (Diptera, chironomidae) larvae exposed to various environmental pollutants: a
      potential biomarker of freshwater monitoring.
AB  - To identify a sensitive biomarker of freshwater monitoring, we evaluated
      pollutant-induced expression of heat shock proteins (HSPs) and hemoglobins (Hbs)
      genes in the larvae of the aquatic midge Chironomus tentans (Diptera,
      Chironomidae). As pollutants, we examined nonylphenol, bisphenol-A, 17alpha
      ethynyl estradiol, bis(2-ethylhexyl) phthalate, endosulfan, paraquat dichloride,
      chloropyriphos, fenitrothion, cadmium chloride, lead nitrate, potassium
      dichromate, benzo[a]pyrene and carbon tetrachloride. We also investigated larval
      growth as a physiological descriptor by measuring changes in the body fresh
      weight and dry weight after chemical exposure. The response of the HSPs gene
      expression by chemical exposure was rapid and sensitive to low chemical
      concentrations but it was not stressor specific. Interestingly, an increase in
      the expression of HSPs genes was observed not only in a stress inducible form
      (HSP70), but also in a constitutively (HSC70) expressed form. The expression of
      Hb genes showed chemical-specific responses: that is, alkyl phenolic compounds
      increased the expression of hemoglobin genes, whereas pesticides decreased the
      expression. As expected, molecular-level markers were more sensitive than
      physiological endpoints, suggesting that gene expression could be developed as an
      early warning biomarker in this animal. The overall results suggest that the
      expression of HSP and Hb genes in Chironomus could give useful information for
      diagnosing general health conditions in fresh water ecosystem. The expression of
      Hb genes, in particular, seems to be a promising biomarker, especially in view of
      the potential of Chironomus larvae as a biomonitoring species and of the
      physiological particularities of their respiratory pigments.

PMID- 16624372
TI  - The effect of sulfide on alpha-glucosidases: implications for starch degradation
      in anaerobic bioreactors.
AB  - Membrane associated alpha-glucosidase activity was investigated in a methanogenic
      bioreactor (MR) and a biosulfidogenic bioreactor (SR). Temperature and pH optima
      studies showed temperature optima of 50 degrees C and pH optima of 8.0 for the
      alpha-glucosidases from both the MR and SR. Sulfide (at a concentration of 150 mg
      l(-1)) resulted in the complete loss of all alpha-glucosidase activity in both
      the MR and SR. beta-Glucosidase activities in our bioreactors were previously
      shown to be stimulated in the presence of sulfide. alpha-Glucosidases, in
      contrast, are inhibited by sulfide. This differential effect of sulfide on alpha
      glucosidase and beta-glucosidase activities is highlighted and is of crucial
      consequence to the respective degradation and utilization of starch and cellulose
      substrates in natural anaerobic environments and anaerobic bioreactors
      specifically designed for the accelerated digestion of wastewater sludge under
      biosulfidogenic conditions.

PMID- 16624373
TI  - Mercury distribution in abiotic and biological compartments within several
      estuarine systems from Argentina: 1980-2005 period.
AB  - Total mercury contents from both abiotic and biological compartments within
      several estuaries from Argentina have been studied since the 1980s. The
      assessment of mercury occurrence in surface sediments, suspended particulate
      matter and crab and fish species from Mar Chiquita coastal lagoon, Bahia Blanca
      estuary and Samborombon Bay (in La Plata river estuary) are included in the
      present study. All samples were analyzed through Cold Vapor-Atomic Absorption
      Spectroscopy, following internationally standardized methods. In all cases
      analytical quality was checked against international reference materials. During
      the 1980s, Hg contents in sediments and SPM, as well as in edible fish species
      from Bahia Blanca estuary were significantly higher (p<0.01) than those of the
      1990s and 2000s, and the large industrial nucleus located in the northern margin
      of this estuary was elsewhere identified as the main source of this metal. A
      permanent monitoring program carried out in 1986 and that is being implemented up
      to the present has demonstrated that Hg concentration values have significantly
      decreased (p<0.01) compared to the values of the 1980s. Both, Mar Chiquita
      coastal lagoon and Samborombon Bay have intermediate mercury levels in their
      biological compartments. In both cases, the possible occurrence of remote sources
      of this metal was considered. Even though, Hg values as determined in sediments
      and suspended particulate matter from Samborombon Bay were the highest ones for
      the whole analyzed period. Both mercury bioaccumulation and biomagnification
      processes were evaluated in the studied estuaries, as well as the potential
      qualification of estuarine foodstuffs for human consumption.

PMID- 16624374
TI  - Assessment of airborne heavy metal pollution by aboveground plant parts.
AB  - Italian stone pine (Pinus pinea L.) and oleander (Nerium oleander L.) leaves,
      bark and wood samples were collected at different sites around an industrial area
      (Huelva, SW Spain) and compared with samples of the same species from a
      background site. Samples were analysed with respect to the following pollutants:
      Al, Ba, Cr, Cu, Fe and Pb by ICP-AES. The suitability of different plant parts as
      biomonitors of pollution was investigated. In pine samples from the polluted
      sites the ratio of concentrations between bark and wood was high for Al, Ba, Cu
      and Fe, whereas no differences were found in samples from the unpolluted area. No
      differences were detected in oleander for the same ratio. In the oleander
      species, the ratio between leaves and wood concentration allowed to distinguish
      between control and polluted sites. The ratio of the concentration between leaves
      and wood was elevated for Al, Ba and Fe in pine samples from the polluted sites.
      The ratio of the concentration in bark or leaves to their concentration in wood
      might be useful to detect inorganic atmospheric pollutants.

PMID- 16624375
TI  - Chelate-induced phytoextraction of metal polluted soils with Brachiaria
      decumbens.
AB  - Chelate-induced phytoextraction with high biomass plant species has been proposed
      for the clean-up of heavy metal polluted soils. In the current work, the effect
      of the application of two different chelating agents, i.e. EDTA and EDDS, on the
      metal phytoextraction capacity of Brachiaria decumbens was studied. Although EDTA
      was, in general, more effective in soil metal solubilization, EDDS, a chelate
      less harmful to the environment, was more efficient inducing metal accumulation
      in B. decumbens shoots than EDTA. Indeed, in a moderately heavy metal polluted
      soil, EDDS caused a 2.54, 2.74 and 4.30-fold increase in Cd, Zn, and Pb shoot
      metal concentration, respectively, as compared to control plants. In this same
      soil, EDTA caused a 1.77, 1.11 and 1.87-fold increase in Cd, Zn, and Pb shoot
      metal concentration, respectively, as compared to control plants. EDDS was also
      more effective than EDTA in stimulating the translocation of metals from roots to
      shoots. B. decumbens plants were able to grow in the metal polluted soils showing
      no visible symptoms of phytotoxicity, which suggests their metal tolerance.
      Finally, B. decumbens, a fast-growing, high biomass, aluminum tolerant plant
      species, that has a well-established agronomic system, fulfills most of the
      requirements for chemically-induced phytoextraction.

PMID- 16624376
TI  - Persistence of polycyclic aromatic hydrocarbons (PAHs) in sewage sludge-amended
      soil.
AB  - The application of sewage sludge as a fertilizer is a common method used to
      improve soil properties. However, sewage sludge may contain various organic
      pollutants including polycyclic aromatic hydrocarbons. In the present study, the
      persistence of PAHs in soils fertilized with different sewage sludge doses was
      compared in relation to the sewage sludge dose applied (30, 75, 150, 300 and 600
      Mgha(-1)) and the content of the polycyclic aromatic hydrocarbons in them. The
      experiment was carried out in two blocks of experimental plots divided according
      to the type of plants grown: field plants and perennial-willow. Sewage sludge
      addition to soils resulted in an increase in the content of polycyclic aromatic
      hydrocarbons in these soils. This increase was proportional to the quantity of
      sewage sludge applied. The results obtained showed that during a 42/54-month
      period, more than half of the individual PAHs introduced into the soil with
      sewage sludge were degraded. The scope of dissipation depended on the sewage
      sludge dose and the use to which the area was put. In the experiment with the
      willow only in the case of the highest sludge dose was a decrease in the PAH
      content above 50% noted; whereas in the case of the experiment with the field
      plants, it was higher by 50% for all sewage sludge doses. In experiment with
      field plants the highest scope of individual PAH disappearance was observed in
      the soil with the sewage sludge dose amounting to 300 Mgha(-1). In experiment
      with willow a relatively high dissipation of individual PAHs (>50%) was found in
      the treatment with the highest sludge dose (600 Mgha(-1)). A wider PAH
      dissipation range in the experiment with field plants was conditioned by the more
      favourable conditions created as a result of the breeding treatments applied.
      Agrotechnical treatments clearly increased the disappearance of the PAHs in those
      soils fertilized with the lowest sewage sludge doses (30 and 75 Mgha(-1)). The
      results obtained showed that the preferred method of treating a light soil
      fertilised with sewage sludges should be a one-year system, with a sludge
      application of 75 Mgha(-1).

PMID- 16624377
TI  - Methods for the preparation of a biodesulfurization biocatalyst using Rhodococcus
      sp.
AB  - Several methods to prepare a biodesulfurization (BDS) biocatalyst were
      investigated in this study using a strain of Rhodococcus sp. 1awq. This bacterium
      could selectively remove sulfur from dibenzothiophene (DBT) via the "4S" pathway.
      DBT, dimethylsulfoxide (DMSO), sodium sulphate and mixed sulfur sources were used
      to study their influence on cell density, desulfurization activity,
      desulfurization ability, and the cost of biocatalyst production. In contrast to
      that observed from bacteria cultured in DBT, only partial desulfurization
      activity of strain 1awq was induced by DBT after cultivation in a medium
      containing inorganic sulfur as the sole sulfur source. The biocatalyst, prepared
      from culture with mixed sulfur sources, was found to possess desulfurization
      activity. With DMSO as the sole sulfur source, the desulfurization activity was
      shown to be similar to that of bacteria incubated in medium with DBT as the sole
      sulfur source. The biocatalyst prepared by this method with the least cost could
      remove sulfur from hydrodesulfurization (HDS)-treated diesel oil efficiently,
      providing a total desulfurization percent of 78% and suggesting its cost
      effective advantage.

PMID- 16624378
TI  - Particulate sulphate and nitrate in Southern England and Northern Ireland during
      2002/3 and its formation in a photochemical trajectory model.
AB  - Daily measurements of sulphate and nitrate are reported from Harwell in southern
      England and Belfast in Northern Ireland for the period 2002/3. When the higher
      percentiles are compared with the mean concentration, nitrate reveals
      considerably greater episodicity than either sulphate or PM(10) (measured by
      TEOM). A photochemical trajectory model using the Master Chemical Mechanism
      scheme has been used to predict daily concentrations of both nitrate and sulphate
      aerosol over the period March to August 2002 at the Belfast and Harwell sites.
      This has been carried out for daily samples using 72, 96 and 120 h air mass back
      trajectories obtained from both the British Atmospheric Data Centre and the
      HYSPLIT on-line service. Additionally, model simulations have been conducted for
      5 trajectories generated through clustering of the trajectories for individual
      days. This reveals an under-prediction of the model associated particularly with
      trajectories originating from the European mainland. In general, the model
      performs reasonably well in simulating concentrations of both nitrate and
      sulphate, which is surprising given that the model does not account for processes
      requiring the presence of liquid water. This suggests that aqueous phase
      oxidation processes may not make a major contribution to airborne sulphate
      concentrations in the U.K. in the spring and summer months. It appears that
      inclusion of explicit ammonium nitrate formation chemistry may be essential to
      reliable prediction of episodic nitrate peaks.

PMID- 16624379
TI  - Soil arsenic availability and the transfer of soil arsenic to crops in suburban
      areas in Fujian Province, southeast China.
AB  - The bioavailability, soil-to-plant transfer and associated health risks of
      arsenic in soils collected from paddy rice fields and vegetable fields in
      suburban areas of some major cities of Fujian Province were investigated. The
      total soil concentrations of arsenic ranged from 1.29 to 25.28 mg kg(-)(1) with a
      mean of 6.09 mg kg(-)(1). Available (NaH(2)PO(4)-extractable) arsenic content
      accounted for 0.7-38.2% of total soil arsenic and was significantly correlated
      with total soil arsenic content. For the vegetable soils, the available fraction
      (ratio of available As to total As) of arsenic decreased with decreasing silt
      (particle size 0.02-0.002 mm) and free iron (DCB extractable) contents and with
      increasing soil pH and organic matter content. The available fraction of arsenic
      in the paddy rice soils increased with increasing free iron and organic matter
      contents and decreasing soil pH and silt content. The correlation of NaH(2)PO(4)
      extractable arsenic with the arsenic concentration of the vegetables was much
      better than that of total As. The transfer factor based on the soil available
      arsenic (TF(avail)) was chosen to compare the accumulation ability of the various
      crops. The TF(avail) values of rice grains (air-dried weight basis) ranged
      between 0.068 and 0.44 and were higher than those of the vegetables, ranging from
      0.001 to 0.12. The accumulation ability of the crops decreased in the order of
      rice>radish>water spinach>celery>onion>taro>leaf mustard>fragrant-flowered
      garlic>pakchoi>Chinese cabbage>lettuce>garlic>cowpea>cauliflower>bottle
      gourd>towel gourd>eggplant. Daily consumption of rice and other As-rich
      vegetables could result in an excessive intake of arsenic, based on the
      provisional tolerable intake for adults for arsenic recommended by WHO.

PMID- 16624380
TI  - Nitrogen in river basins: sources, retention in the surface waters and peatlands,
      and fluxes to estuaries in Finland.
AB  - Nitrogen export from diffuse and point sources and its retention in the major
      river basins of Finland is quantified and discussed. The estimated total export
      from river-basins in Finland was 119,000 tonnes N a(-1) for the period 1993 to
      1998 based on N export from different land use types defined in a GIS-based
      assessment model, incorporated with estimates of N inputs from atmospheric
      deposition and point sources. Agriculture contributes 38% of the total export,
      varying in the range 35-85% in the south-western basins and 0-25% in the northern
      basins. This estimate of N export from agriculture was based on regional N
      balances together with data from small agricultural research catchments. Forestry
      contributes on average 9%, with increasing dominance towards eastern and northern
      parts of the country: from 2% to 15% in the southern-mid-western Finland basins
      to 10-30% in the large northern basins. 'Background' N export from forests on
      both mineral and organic soils contributes 27% on average; in the northern basins
      it may contribute from 40% up to 90% of the total load. The estimate was
      calculated based on practically all data available from 42 small, experimental
      catchments in Finland. Of the total N input to Finnish river-systems, 0% to 68%
      was retained in surface waters and/or peatlands, with a mean retention of 22%.
      The highest retention of N (36-61%) was observed in the basins with the highest
      lake percentages. The lowest retention (0-10%) of N was in the coastal basins
      with practically no lakes. In the national N mass balance, 38,000 tonnes N a(-1)
      (32%) was estimated as lake retention and 4,000 tonnes N a(-1) (3%) as retention
      in peatlands. On the basis of mass balances and sensitivity analysis, retention
      was in most cases estimated to be in the range of 7.5-12.5 kg ha(-1)a(-1) in
      lakes and 0-1.5 kg ha(-1)a(-1) in peatlands. The model results were tested using
      the split-sample technique and uncertainty estimates for different data sources
      are provided and discussed.

PMID- 16624381
TI  - Characterization of fine particle sources in the Great Smoky Mountains area.
AB  - A source apportionment study to characterize sources of fine particles in the
      Great Smoky Mountains area was conducted analyzing ambient PM(2.5) (particulate
      matter< or =2.5 microm in aerodynamic diameter) speciation data collected at a
      Interagency Monitoring of Protected Visual Environments (IMPROVE) monitoring
      site. A total of 1442 samples collected between March 1988 and December 2003
      analyzed for 30 elemental species were analyzed with the application of the
      positive matrix factorization (PMF). Eight major sources were extracted: summer
      high secondary sulfate (55%), carbon-rich secondary sulfate (16%), summer-low
      secondary sulfate (2%), gasoline vehicle emissions (13%), diesel emissions (1%),
      airborne soil (6%), industry (5%), and secondary nitrate (2%). The contributions
      from the carbon-rich secondary sulfate particles are likely a combination of
      local and regional influences of the biogenic as well as anthropogenic secondary
      particles. The compositional profiles for gasoline vehicle and diesel emissions
      are similar to those identified in other US areas. Backward trajectories indicate
      that the high impacts of airborne soil were likely caused by Asian and Saharan
      dust storms. This study would assist in the implementation plan development for
      attaining the air quality standards for PM(2.5), regional haze rule planning, and
      source-specific community epidemiology.

PMID- 16624382
TI  - Distribution of phytoplankton in the Three-Gorge Reservoir during rainy and dry
      seasons.
AB  - After damming of the Yangtze River, in order to explore the impacts of the Three
      Gorge Dam (TGD) on the aquatic ecosystem, phytoplankton composition, abundance
      and biomass spatial distribution were studied in the Three-Gorge Reservoir (TGR),
      and the closest upstream anabranch Xiangxi River, which is 38 km away from the
      Three-Gorge Dam (TGD) during August (rainy season) 2004 and April (dry season)
      2005. In surveys, 6 transects (2 downstream and 4 cross-stream) and 25 stations
      have been investigated and 314 samples were collected from the surface to the
      river bed with water samplers. In TGR, 63 taxa and 60 taxa were identified in the
      rainy and dry seasons, respectively. In the Xiangxi River, 39 taxa were observed
      in the rainy and dry seasons. Algal blooms occurred in the Xiangxi River and at
      the influx region of the Yangtze and Xiangxi in both seasons, but had not
      occurred prior to damming. In the rainy season, the dominant species was
      Chroomonas acuta with 1.84x10(7) cells l-1, and in the dry season the dominant
      species were Asterionella formosa and Cryptomonas ovata with 1.34x10(7) cells l-1
      and 1.79x10(6) cells.l-1, respectively. In the main channel of TGR, there were no
      significant correlations between phytoplankton abundance and the concentrations
      of the main soluble nutrients. In the Xiangxi River, significant negative
      correlations were observed between phytoplankton abundance and nitrate (Spearman,
      p<0.01, n=21), phosphate (Spearman, p<0.05, n=21) and silicate (Spearman, p<0.01,
      n=21) in the rainy season, and similar correlations were also observed with
      nitrate (Spearman, p<0.05, n=28) and silicate (Spearman, p<0.01, n=28), but not
      with phosphate in the dry season. Since the damming of the Yangtze River,
      eutrophication in the anabranch within the backwater has occurred and become
      severe, and the frequency of algal bloom within TGR and anabranches is expected
      to increase.

PMID- 16624383
TI  - Evaluation of total lipids using enzymatic methods for the normalization of
      persistent organic pollutant levels in serum.
AB  - The human exposure to persistent organic pollutants (POPs) is conveniently
      assessed through analysis of blood serum or plasma and the POPs concentrations
      are traditionally expressed on a lipid weight basis. Enzymatic determinations of
      total lipid (TL) content in serum, which imply the measurement of individual
      lipid classes, such as triglycerides (TG), cholesterol (CHOL) and phospholipid
      (PL), use small amounts of serum/plasma (<100 microl). These have also become a
      more precise and less laborious alternative for the gravimetric lipid
      determinations which were preferred in the past. However, PL are not routinely
      measured in most clinical laboratories and therefore, TL values are often
      predicted from formulas based on measurements of only TG and CHOL. In the present
      study, a large data set (n=483) from Belgian, Swedish and Norwegian populations
      was used to compute a new formula for TL [TL=1.33*TG+1.12*CHOL+1.48 (g/l)] by
      means of multiple linear regression. A very good correlation (r=0.949, p<0.001)
      was found between TL values calculated with the proposed formula and TL values
      obtained by summation of TG, CHOL and PL. Statistically different values of TL
      were computed when different previously published formulas were compared, which
      can have a strong influence on the calculation of lipid-normalized concentrations
      of POPs. Nevertheless, TL values derived using a mathematical formula which
      includes only TG and CHOL will be less accurate than TL values obtained by
      summation of TG, CHOL and PL, which should be the calculation method of choice if
      PL measurements are available.

PMID- 16624384
TI  - Initial studies on an in vivo action spectrum for melanoma induction.
AB  - Vitamin D production is initiated by exposure of 7-dehydrocholesterol in the skin
      to the UVB (280-320 nm) component of sunlight, resulting in the formation of
      photoproducts, which are subsequently metabolically activated to biologically
      active moieties in a series of dark reactions as described elsewhere in this
      symposium. Irradiation of the skin with UVB has, however, other effects not all
      of which are beneficial. Most notable is the initiation of skin cancer. Non
      melanoma skin cancer is clearly initiated by UVB but for the most lethal of the
      skin cancers, cutaneous malignant melanoma, although associated with sunlight
      exposure, the wavelengths responsible have not been clearly identified. Using a
      mouse model for UV-induced melanoma, we have recently shown that UVB, not UVA
      (320-400 nm), is also responsible for melanoma initiation. A balance therefore
      needs to be struck between the healthy effects of exposure to UVB in sunlight-
      vitamin D formation--and the deleterious effects of which the most potentially
      serious is melanoma initiation. A powerful tool in determining this balance would
      be an understanding of the action spectra or wavelength dependence for each of
      these effects. Here we describe methodologies, approaches and potential pitfalls
      for action spectra determination illustrated by our experience with the HGF/SF
      transgenic mouse model for UV-induced melanoma.

PMID- 16624385
TI  - Public awareness regarding UV risks and vitamin D--the challenges for UK skin
      cancer prevention campaigns.
AB  - Since 1970s, incidence rates for malignant melanoma have been among the fastest
      rising of all cancers in the UK. Compared to other cancers, melanoma affects
      disproportionately more young people, and non-melanoma skin cancers are the most
      commonly diagnosed, with over 100,000 new cases estimated in the UK annually.
      Government targets to reduce skin cancer incidence have led working groups and
      prevention campaigns to be set up in the belief that moderating UV exposure will
      help. An increased awareness of skin cancer has clearly played a role in curbing
      mortality from the disease, but translating knowledge into behaviour change in
      this context is a slow and complex process, and campaigns need to be sustained if
      they are to impact on incidence. A growing body of literature suggesting a cancer
      protective role for vitamin D and sun exposure presents further challenges for
      skin cancer prevention campaigns, no more so than when exaggerated claims for the
      health benefits of sunbathing make the media spotlight. The UK population tend to
      need little encouragement to make the most of sunshine, and this is especially
      true for the younger generation who most need to take care. Public health
      messages to avoid the midday sun, not to burn and to protect children should not
      adversely affect outdoor activity or population vitamin D levels, but it is
      important that they are targeted to those most at risk and are consistent. More
      research is required to establish optimal levels of vitamin D and how to safely
      achieve them in a heterogeneous population. In the meantime, hasty alterations of
      public health messages are likely to prove counterproductive.

PMID- 16624387
TI  - Peritoneal carcinomatosis after laparoscopic radical hysterectomy for early-stage
      cervical adenocarcinoma.
AB  - BACKGROUND: The risk of wound metastasis after laparoscopic management of early
      stage cervical cancer is well known, but there are few data on peritoneal
      carcinomatosis of cervical adenocarcinoma. CASE: We report the first case of
      peritoneal carcinomatosis occurring in a woman with FIGO stage Ib1 cervical
      adenocarcinoma who underwent laparoscopic type III radical hysterectomy and
      bilateral pelvic lymphadenectomy (sentinel node procedure) followed by vaginal
      brachytherapy. A peritoneal recurrence was diagnosed 16 months after surgery and
      was treated with chemotherapy and laparotomy. CONCLUSION: Laparoscopy for
      cervical adenocarcinoma may carry a risk of peritoneal dissemination.

PMID- 16624386
TI  - Antiproliferative and apoptotic effects of zinc-citrate compound (CIZAR(R)) on
      human epithelial ovarian cancer cell line, OVCAR-3.
AB  - OBJECTIVE: Zinc inhibits the growth of several carcinoma cells through induction
      of cell cycle arrest and apoptosis. The intracellular concentration of zinc and
      its dynamic changes are critically important in cell biology. We investigated the
      effects of zinc-citrate compound (CIZAR) on normal human ovarian epithelial cells
      (NOSE) and human epithelial ovarian cancer cell line, OVCAR-3. METHODS: To
      investigate the potential effect of CIZAR on cell growth and survival, cells were
      treated with different doses and exposed to different times. Intracellular
      concentration of zinc was measured by colorimetric assay. Mitochondrial aconitase
      activity was determined in cell extracts using aconitase assay. The flow
      cytometric assay, DNA laddering, and morphological analysis were done to
      investigate cytotoxic effects of CIZAR. Molecular mechanism of cell death was
      investigated by p53, Bcl-xL, Bcl-2, Bax protein, activity of caspase-3 and -12,
      and activity of telomerase. RESULTS: CIZAR-induced zinc accumulation in OVCAR-3
      cells was higher than that in NOSE cells. CIZAR(R) treatment resulted in a time-
      and dose-dependent decrease in cell number in OVCAR-3 cells in comparison with
      NOSE cells. M-aconitase activity was significantly decreased in OVCAR-3 cells
      within 4 h exposure to CIZAR but relatively constant in NOSE cells. The flow
      cytometric assay, DNA laddering, and morphological analysis indicated apoptosis
      in OVCAR-3 cells but not in NOSE cells. CIZAR increased the expression of
      p21(waf1) which is a part of p53-independent pathway and induced reduction of
      telomerase activity. CIZAR reduced expression of Bcl-2 and Bcl-xL proteins but
      induced expression of Bax protein. CIZAR induced apoptosis of OVCAR-3 cells by
      activation of caspase-12 and caspase-3 pathway. CONCLUSIONS: Exposure to CIZAR
      induces apoptosis in OVCAR-3 cells which accumulate high intracellular levels of
      zinc, but not in NOSE cells, which do not accumulate high levels of zinc.
      CIZAR(R) prevents the proliferation of OVCAR-3 cells by inactivation of m
      aconitase activity and induces apoptosis by induction of proapoptotic gene (Bax),
      repression of antiapoptotic genes (Bcl-2, Bcl-xL), and consequently activation of
      caspase-3. CIZAR also induced activation of caspase-12. The CIZAR will offer new
      window in prevention and treatment of epithelial ovarian cancer.

PMID- 16624388
TI  - What is the best protocol of single-agent methotrexate chemotherapy in
      nonmetastatic or low-risk metastatic gestational trophoblastic tumors? A review
      of the evidence.
AB  - OBJECTIVE: Gestational trophoblastic diseases (GTD), a group of rare placenta
      disorders, have a varying potential for invasion, either local, or remote under
      the form of metastases, and are definitely cured by chemotherapy in 85 to 99% of
      cases. Single-agent methotrexate is the usual primary treatment for women with
      low-risk trophoblastic tumors (TT), yet various regimens are currently used
      worldwide. We reviewed these regimens and the available evidence for evaluating
      their respective efficacy and tolerance. METHODS: We performed an exhaustive
      literature search and applied the French agency for evaluation in healthcare
      (HAS) methodology for critical appraisal and level of evidence. We summarised the
      protocols used in the selected studies and their respective results regarding
      efficacy and toxicity. RESULTS: We selected 18 original studies on the efficacy
      and tolerance of methotrexate used alone or in association with folinic acid for
      the treatment of nonmetastatic or low-risk metastatic trophoblastic tumors. Among
      these 18 studies, 15 were retrospective series, 3 were prospective series without
      any control group, and none were controlled clinical trial. We identified four
      main chemotherapy regimens and two very different strategies for repeating the
      treatment courses. It was not possible to perform a meta-analysis due to the lack
      of controlled clinical trials. Because all studies were observational with no
      control group and methods were heterogeneous for scoring women, setting criteria
      for starting therapy, defining remission, and collecting information on adverse
      events, we found no objective element allowing recommending one protocol rather
      than another. CONCLUSION: Objective comparison should be addressed in the scope
      of comparative trials organised at the national or even international level.
      However their feasibility is highly problematic for rare diseases such as GTD.
      International collaborative works should be encouraged to reduce practice
      variations and allow a better comparability between strategies.

PMID- 16624389
TI  - Psammoma bodies in cervicovaginal cytology specimens: a clinicopathological
      analysis of 31 cases.
AB  - BACKGROUND: Psammoma bodies in cervicovaginal cytology specimens are associated
      with malignant and benign conditions. Few studies have evaluated which features
      distinguish patients with underlying malignancy from those with benign
      conditions. METHODS: Pathology files were searched for cervicovaginal specimens
      having psammoma bodies. The cytology specimen was assessed for the background,
      glandular atypia, squamous atypia, and presence of non-psammomatous
      calcifications. Clinical data was obtained from chart review. RESULTS: Nineteen
      women (mean age 42.7 years) had benign outcomes. None had signs or symptoms
      suggesting malignancy. None had highly atypical or malignant appearing glandular
      cells. Twelve women had malignant neoplasms (mean age 56 years), including 6 with
      recurrent disease. Four women without prior malignancy had worrisome signs
      including bleeding or mass. All six women with prior malignancy had signs of
      recurrent disease. All specimens contained highly atypical or malignant glandular
      cells. CONCLUSIONS: The only cytologic feature predictive of outcome was the
      presence of highly atypical glandular cells in the specimen (P = 0.001), but
      these cells may be few. Women with underlying malignancy were older than those
      with benign outcome (P = 0.014) and more likely to be postmenopausal (P = 0.05).
      Women with malignancy had signs that warranted additional investigation whereas
      those with benign outcome were usually asymptomatic (P = 0.001).

PMID- 16624390
TI  - Primary peritoneal psammocarcinoma: a case presenting synchronously with bowel
      carcinoma.
AB  - BACKGROUND: Psammocarcinomas are rare epithelial tumors usually originating from
      the ovarian surface epithelium or the peritoneum. In our case, a peritoneal
      psammocarcinoma was incidental surgical finding during laparotomy. CASE: An 83
      year-old woman underwent surgery for bowel obstruction. Intraoperativelly, a
      bowel carcinoma was documented. Notable were numerous small disseminated
      peritoneal nodules that studded the omentum and bowel serosa. At reintervention,
      similar nodules were observed in the serosal surface of the two ovaries, uterus,
      left salpinx, and omentum. The nodules corresponded histologically to
      psammocarcinoma of peritoneal origin. Despite not receiving adjuvant treatment,
      the patient is still alive 53 months following the second operation, without
      signs of metastases or disease recurrence. CONCLUSION: Though unpredictable,
      psammocarcinomas might run an indolent course, and decisions regarding management
      should be individualized.

PMID- 16624392
TI  - Recurrent basosquamous cell carcinoma of the vulva.
AB  - BACKGROUND: Basosquamous cell carcinoma (BSC) of the vulva is a rare entity with
      interesting prognostic and therapeutic implications. Currently, there is no
      definitive treatment due to its low incidence. CASE: A case of recurrent BSC of
      the vulva treated with unilateral radical vulvectomy and unilateral lymph node
      dissection is reported. CONCLUSION: BSC is a rare disorder of the vulva. The
      metastatic potential of this tumor is not fully understood, but likely is
      intermediate between squamous cell carcinoma and basal cell carcinoma. Local
      recurrence is common and close follow-up is warranted.

PMID- 16624391
TI  - Phenethyl isothiocyanate (PEITC) inhibits growth of ovarian cancer cells by
      inducing apoptosis: role of caspase and MAPK activation.
AB  - OBJECTIVE: Epithelial ovarian cancer has the highest mortality rate among
      gynecologic cancers. Chemotherapy is an essential component of its treatment.
      While isothiocyanates are known to possess chemopreventive effects against
      various cancers, yet little is known about their chemotherapeutic potential in
      ovarian cancer (OC). In the present study, we examined the antiproliferative and
      apoptotic effect of phenethyl isothiocyanate (PEITC), a naturally occurring
      isothiocyanate on OVCAR-3 cells. METHODS: Cytotoxic activity of PEITC on OVCAR-3
      cells was determined using cell proliferation, apoptosis (DNA fragmentation and
      TUNEL assay) and caspase-activation studies. The role of PARP-1, Bax, and Bcl-2
      in apoptosis was analyzed by Western blotting. Activation of JNK1/2, p38, Akt,
      ERK1/2, and c-Myc was examined by immunoblotting. Specific inhibitors of
      caspases, JNK1/2, p38, and MEK were used to corroborate these data. RESULTS:
      PEITC was cytotoxic to OVCAR-3 cells, and inhibited proliferation in a dose
      dependent fashion (IC(50) = 23.2 microM). PEITC induced apoptosis by activating
      caspase-3 and -9, without capsase-8 activation. Anti-apoptotic Bcl-2 levels were
      suppressed while pro-apoptotic Bax levels were enhanced. PEITC suppressed
      activation of Akt, ERK1/2, and the expression of transcription factor c-Myc,
      while simultaneously activating pro-apoptotic p38 and JNK1/2. Specific inhibitors
      of caspase-3 and -9, JNK1/2, and p38 reversed the cytotoxic effect of PEITC.
      CONCLUSIONS: These findings demonstrate that PEITC exhibits cytotoxicity towards
      OVCAR-3 cells and induces apoptosis via caspase-9 and -3 pathways. PEITC inhibits
      Akt, ERK1/2 survival signaling, and c-Myc while simultaneously activating pro
      apoptotic p38 and JNK1/2. Systematic preclinical and clinical trials with PEITC
      in ovarian cancer are indicated.

PMID- 16624393
TI  - Arsenic trioxide (As(2)O(3)) inhibits peritoneal invasion of ovarian carcinoma
      cells in vitro and in vivo.
AB  - OBJECTIVES: To study the role of arsenic trioxide (As(2)O(3)) in regulating
      peritoneal invasive activity of ovarian carcinoma cells in vitro and in vivo.
      METHODS: The effects of As(2)O(3) on human ovarian cancer cell lines (3AO, SW626
      and HO-8910PM) migration, invasion and adhesion with tumor cells and human
      peritoneal mesothelial cells (HPMC) were observed by means of cell migration
      test, cell invasion test and cell adhesion test. The effects of As(2)O(3) on MMP
      2, MMP-9, TIMP-1 and TIMP-2 gene expressions and protein expressions of tumor
      cells were determined by RT-PCR and ELISA, respectively. In animal experiments,
      ovarian tumor cells were implanted into abdominal cavity of nude mice and then
      the nude mice were treated by intraperitoneal injection of different doses
      As(2)O(3). The foci on the surface of peritoneum were counted. RESULTS: As(2)O(3)
      inhibited tumor cells migration, invasion and adhesion with HPMC in a dose
      dependent manner, while the same treatment enhanced tumor cell-tumor cell
      interactions. As(2)O(3) inhibited mRNA and protein expressions of MMP-2, MMP-9
      and TIMP-2 of tumor cells. In contrast, As(2)O(3) increased mRNA and protein
      expressions of TIMP-1. As(2)O(3) could reduce tumor cells peritoneal metastasis
      in nude mice. CONCLUSION: As(2)O(3) inhibits in vitro and in vivo peritoneal
      invasive activity of ovarian carcinoma cells in a dose-dependent manner. Its anti
      invasive activity may be the results of reduced cell motility, inhibited
      attachment of tumor cells to HPMC and enhanced tumor cell-tumor cell interaction,
      as well as down-regulation of MMP-2 and MMP-9 levels and up-regulation of TIMP-1
      level.

PMID- 16624394
TI  - Thyrotropin-releasing hormone increased heat production without the involvement
      of corticotropin-releasing factor in neonatal chicks.
AB  - Thyrotropin-releasing hormone (TRH) is a hypothalamic signal in the hypothalamic
      pituitary-thyroid (HPT) axis, and is well known as a hyperthermic hormone in the
      brain of chicks. The thermogenetic effect leads to the hypothesis that central
      TRH increases heat production (HP) in chicks. The purpose of the present study
      was to clarify whether central TRH affects HP of neonatal chicks, and if such an
      effect is mediated by corticotropin-releasing factor (CRF) since the
      thermogenetic effect of TRH is mediated by CRF. Intracerebroventricular (ICV)
      injection of TRH (14 and 55 nmol) dose-dependently increased oxygen consumption,
      carbon dioxide production and HP, and a similar effect was also observed with CRF
      (2.1 and 21 pmol). The TRH-induced increase in HP could not be attenuated by
      astressin, a CRF receptor antagonist, while the effect of CRF was completely
      diminished by astressin. The present study demonstrates that central TRH
      increases HP in chicks but the effect was not related to CRF.

PMID- 16624395
TI  - Selective blockade of NK2 or NK3 receptors produces anxiolytic- and
      antidepressant-like effects in gerbils.
AB  - There is a growing interest in the potential anxiolytic- and antidepressant-like
      effects of compounds that target neurokinin receptors. Since the structure and
      the pharmacology of the human neurokinin receptor resembles that of gerbils,
      rather than that of mice or rats, we decided to investigate the anxiolytic- and
      /or antidepressant-like effects of NK1 (SSR240600), NK2 (saredutant) and NK3
      (osanetant) receptor antagonists in gerbils. It was found that saredutant (3-10
      mg/kg, p.o.) and osanetant (3-10 mg/kg, p.o.) produced anxiolytic-like effects in
      the gerbil social interaction test. These effects were similar to those obtained
      with the V1b receptor antagonist SSR149415 (3-10 mg/kg, p.o.), diazepam (1 mg/kg,
      p.o.) and buspirone (10 mg/kg, p.o.). Fluoxetine and SSR240600 were devoid of
      effects in this test. In the tonic immobility test in gerbils, saredutant (5-10
      mg/kg, i.p.) and osanetant (5-10 mg/kg, i.p.) produced similar effects to those
      observed with fluoxetine (7.5-15 mg/kg, i.p.), SSR149415 (10-30 mg/kg, p.o.) and
      buspirone (3 mg/kg, i.p.). Diazepam and SSR240600 were inactive in this paradigm.
      In conclusion, the present study indicates further that NK2 and NK3 receptor
      antagonists may have therapeutic potential in the clinical management of anxiety
      and depression.

PMID- 16624396
TI  - Effects of D-amphetamine on defensive behaviors related to fear and anxiety.
AB  - In rodents, the administration of amphetamine has been associated with increased
      locomotor activity and stereotypy, and an emerging body of evidence suggests that
      it also enhances anxiety-like behavior in a number of animal models.
      Ethoexperimental analyses have outlined an array of defensive behaviors to threat
      that are responsive to anxiolytic, panicolytic-like and panicogenic agents,
      suggesting that the characterization of amphetamine effects on defense may
      provide further insights into the emotionality consequences of this drug. In
      Experiment 1, intraperitoneal administration of amphetamine (1 and 5 mg/kg, i.p.)
      on defensive behavior elicited by a predatory threat stimulus was assessed via
      time sampling analysis. Amphetamine dose-dependently suppressed freezing while
      potentiating locomotor activity. In Experiment 2, amphetamine was administered
      intravenously and animals were tested in a Rat Runway Test (RRT), designed to
      individually elicit a variety of defensive behaviors to a conspecific threat. All
      three doses of amphetamine (1, 2 and 5 mg/kg) produced robust changes in
      defensive responding by increasing directional flight behavior, jump escapes and
      upright/orientations. The results are in agreement with those of another
      psychostimulant, cocaine, and support a previously hypothesized link between
      flight and panic.

PMID- 16624397
TI  - Smoking behavior and its influencing factors in a national-representative sample
      of Iranian adolescents: CASPIAN study.
AB  - OBJECTIVES: To determine the national prevalence of smoking among Iranian youths
      and its environmental influencing factors. METHODS: This study was performed in
      2003-2004 among 11,966 school students, ages 11-18 years, selected by multi-stage
      random cluster sampling from 20 provinces in Iran. The participants filled out
      self-administered anonymous questionnaires. RESULTS: The prevalence of self
      reported cigarette smoking was 14.3%, with a higher prevalence in boys than in
      girls (18.5% vs. 10.1%, respectively, P < 0.001), and in high school than in
      middle school students (17.4% vs. 10.6%, respectively, P < 0.001). Overall, 42.2%
      of smokers were daily smoker, and the rest were occasional smoker. The mean age
      of the first attempt to smoke was 13.2 +/- 2.5 years with no significant gender
      difference but was significantly lower in daily than in occasional smokers. The
      place of the first attempt to smoke was mostly in friend parties (41.6%) and
      traditional teahouses (23.2%) for boys and the family parties (37.1%) and the
      traditional teahouses (27.4%) for girls. The higher school level and having a
      tobacco user at home significantly increased the likelihood of smoking in
      adolescents, with the highest odds ratio (OR) found for having a smoker sister in
      girls (OR = 4.5, 95%CI, 2.5, 8.2), and having a smoker brother in boys (OR = 2.4,
      95%CI, 2.03, 3.05). CONCLUSION: Smoking is becoming as a major public health
      threat among Iranian youths. Control measures should be considered not only for
      cigarette smoking, but also for the socially accepted habit of water pipe use
      that is revived in traditional teahouses.

PMID- 16624398
TI  - A cluster-randomized trial on smoking cessation in German student nurses.
AB  - OBJECTIVES: To evaluate the effect of a specific intervention on smoking
      cessation in health professionals. METHODS: Between 2003 and 2004, a cluster
      randomized trial was performed in 32 schools of nursing with 956 student nurses
      in Southwest Germany. Students in the intervention group received three teaching
      units each lasting 1 day on how to give advice to people who want to stop
      smoking. The program addressed only nurses' professional role and not their
      individual smoking behavior. After a follow-up of 13 months, the change in
      smoking status was determined. Secondary endpoints included changes of smoking
      related factors like stages of smoking or knowledge about health risks. RESULTS:
      Change of smoking status in the desired direction (stopping smoking or not
      starting smoking) occurred less often in the intervention than in the control
      group, but the difference did not reach statistical significance (odds ratio
      0.69, 95% confidential interval: 0.43, 1.10). The program was successful in
      delivering medical knowledge (P=0.0056) and in enhancing competence in giving
      advice to smokers (P<0.0001). CONCLUSIONS: The applied approach is able to
      improve student nurses' medical knowledge and to augment their competence in
      giving advice to smokers, but it is not an effective strategy to reduce their own
      smoking behavior.

PMID- 16624399
TI  - Community-based study on summer-winter differences of component of metabolic
      syndrome in Kinmen, Taiwan.
AB  - BACKGROUND: A community-based study was conducted to investigate summer-winter
      differences of component of metabolic syndrome in Kinmen, Taiwan. METHODS: A
      total of 8251 residents aged 40 and over were enrolled in the mass survey in
      Kinmen. They were investigated while on summer (July and August) and winter
      vacation (January and February) during 2000-2003. Demographics, physical
      examination findings, lifestyle variables and biochemical data were collected.
      RESULTS: After controlling for age, body mass index, diet, lifestyle and other
      risk factors for component of metabolic syndrome, there were independent and
      significant relationships between summer-winter difference and component of
      metabolic syndrome. Winter season was positively correlated with blood pressure,
      fasting plasma glucose level, high-density lipoprotein-cholesterol (HDL-C) and
      waist circumference, but was negatively associated with fasting triglycerides and
      metabolic syndrome. CONCLUSIONS: Summer season is positively associated with
      hypertriglyceridemia, low HDL-C and metabolic syndrome. These findings imply that
      cross-sectional, experimental and cohort studies of component of metabolic
      syndrome or metabolic syndrome should take season into account as possible
      confounding effects.

PMID- 16624400
TI  - Ascertaining variation in hospitalization risk among immigrants using small area
      analysis.
AB  - INTRODUCTION: Data on hospitalization of immigrants to the United States are
      sparse, but small area analysis may improve the utility of existing data.
      METHODS: Applying logistic regression analysis to 2000 census and hospitalization
      data for New York City, we examined the odds of hospital admission by major
      diagnostic category and global region of birth after controlling for covariates.
      We used individual-level covariates to control for age, race, and gender. By
      matching the patient's zip code of residence to census data, we then added median
      household income, the proportion of persons born in a particular global region,
      and the proportion of foreign-born persons living in the same zip code as
      independent variables. RESULTS: The total proportion of foreign-born persons in a
      zip code predicts a lower hospitalization rate for most major diagnostic
      categories and most foreign-born groups. However, Africa-born persons have a
      higher odds of hospitalization for most major diagnostic categories - up to 1.79
      (95% confidence interval 1.73, 1.86) for blood and blood forming disorders -
      relative to native-born persons. The odds of hospitalization among Africa-born
      persons for most conditions are over 3 times higher than other foreign-born
      groups. Hospitalization odds for Latin American-born persons were also higher
      than native-born persons across major diagnostic categories. CONCLUSION: Small
      area analysis generally predicts hospitalization rates that coincide with
      mortality studies and may serve as a useful tool for hypothesis testing in
      immigrant health.

PMID- 16624401
TI  - Photocoupling of fibronectin to titanium surfaces influences keratinocyte
      adhesion, pellicle formation and thrombogenicity.
AB  - OBJECTIVES: Coating of implant surfaces with biomolecules can influence basic
      host responses and enhance subsequent tissue integration. The biological factors
      have to be immobilized on the implant material. Human fibronectin (Fn) was used
      as a model protein and covalently coupled to titanium (Ti) surfaces via
      silanization and an anthraquinone linker. The impact on several aspects of
      initial host/biomaterial interactions (keratinocyte adhesion, platelet
      interactions and pellicle formation) was studied. METHODS: Coupling efficiency
      was characterized by immunological techniques. The effects of coupled Fn on
      initial host/biomaterial interactions were assessed. Cell adhesion and spreading
      were investigated by fluorescent staining, pellicle formation by an acoustic
      sensor system (quartz crystal microbalance with dissipation, QCM-D), and platelet
      adhesion as one parameter mediating the inflammatory response by scanning
      electron microscopy (SEM) and immunological assays. RESULTS: Coupling efficiency
      was related to irradiation time used for photochemical coupling of the UV
      activated anthraquinone to the silanized Ti surface. With an optimized protocol,
      the amount of Fn coupled to the surface could be almost doubled compared to
      standard dip-coating methods. On the anthraquinone-coupled Fn coatings, cell
      adhesion and spreading of human keratinocytes was significantly enhanced. Online
      detection of pellicle formation revealed strong reversibility of saliva protein
      adhesion on Fn coated surfaces compared to the pure Ti surface. Furthermore, the
      Fn coated Ti showed a low thrombogenicity. SIGNIFICANCE: This study suggests that
      anthraquinone-coupled biological coatings may be useful for biofunctionalization
      of Ti dental implants by enhancement of soft tissue re-integration (restoration
      of the epithelial seal) combined with diminished pellicle formation.

PMID- 16624402
TI  - Oxidative stress response of European flounder (Platichthys flesus) to cadmium
      determined by a custom cDNA microarray.
AB  - The monitoring of the impact of chemical pollutants upon marine ecosystems
      commonly employs a multi-biomarker approach. Functional genomics, using cDNA
      microarrays, allows for a comprehensive view of how an organism is responding to
      an exposure, with respect to changes in gene expression. Differentially expressed
      mRNAs were first isolated from livers of European flounder by means of
      suppressive, subtractive hybridisation. A clone set containing a total of 284
      different potentially differentially expressed mRNAs was produced, of which 84
      were tentatively identified. These were combined with previously cloned known
      stress genes isolated by degenerate PCR to produce a custom 500-clone microarray
      platform with each clone arrayed to four spots. Subsequent array experiments
      using cadmium-treated flounder detected up-regulation of 27 transcripts,
      including Cu/Zn superoxide dismutase, thioredoxin, a peroxiredoxin and a
      glutathione-S-transferase, reflecting oxidative stress in exposed flounder, while
      CYP1A expression was down-regulated. These changes were confirmed by real-time
      PCR. The array experiment highlighted a number of candidate genes for further
      analysis as potential novel biomarkers of cadmium exposure and demonstrated the
      applicability of the custom microarray approach in the study of the effects of
      toxicants.

PMID- 16624403
TI  - Possible tetramerisation of the proteasome maturation factor
      POMP/proteassemblin/hUmp1 and its subcellular localisation.
AB  - The proteasome is a multisubunit complex with a central role in non-lysosomal
      proteolysis and the processing of proteins for presentation by the MHC class I
      pathway. The 16kDa proteasome maturation protein POMP (also named proteassemblin
      or hUmp1) acts as a chaperone and is essential for the maturation of the 20S
      proteasome proteolytic core complex. However, the exact mechanism, timing and
      localisation of mammalian proteasome assembly remains elusive. We sought to
      investigate the localisation of POMP within the cell and therefore purified the
      protein and produced a polyclonal antibody. For immunisation, POMP was
      overexpressed and purified from a bacterial GST-system. Interestingly, after
      removal of the GST-tag, POMP was hardly detectable by Coomassie blue- and Ponceau
      red-staining. However, with a reverse zinc-staining, the protein could easily be
      visualised. POMP was gel-filtrated and eluted from a calibrated chromatography
      column with an apparent molecular weight of approximately 64kDa, suggesting that
      it forms tetramers. Moreover, localisation studies by immunofluorescence
      stainings and confocal microscopy revealed that POMP is present in the cytoplasm
      as well as in the nucleus.

PMID- 16624404
TI  - Induction of apoptosis and down regulation of cell cycle proteins in mantle cell
      lymphoma by flavopiridol treatment.
AB  - Typical mantle cell lymphoma (MCL) is a distinct B-cell non-Hodgkin's lymphoma
      associated with over-expression of cyclin D1 related to translocation between the
      IgH and BCL-1 genes. Due to the important functional interaction between cyclin
      D1 and cyclin dependent kinases, cyclin dependent kinase inhibitors such as
      flavopiridol are under consideration for treatment of patients with MCL. The
      present study investigated the in vitro effects of flavopiridol on the MCL cell
      line (JeKo-1). Flavopiridol at a dose of 10nmol/L induced apoptosis by 6h of
      treatment as noted by flow cytometric analysis, morphologic examination and
      Western blotting. The cleavage of procaspase-3 and PARP and the decrease of
      flavopiridol-induced apoptosis by pan-caspase inhibition suggested that the
      caspase pathway serves an important role in the apoptotic process. Furthermore,
      MCL cells exposed to flavopiridol showed down regulation of key cell cycle
      proteins acting at the restriction point control between the G1 and S phases. The
      onset of flavopiridol-induced apoptosis also coincided with the down regulation
      of Mcl-1, anti-apoptotic protein. Collectively, our data indicates that
      flavopiridol may have significant therapeutic potential in the context of MCL.

PMID- 16624405
TI  - pIT3, a cryptic plasmid isolated from the hyperthermophilic crenarchaeon
      Sulfolobus solfataricus IT3.
AB  - The plasmid pIT3 (4,967 bp) was isolated from the hyperthermophilic archaeon
      Sulfolobus solfataricus, strain IT3. The completely sequenced plasmid contains
      six open reading frames (ORFs), the largest (ORF915) spanning more than half of
      the plasmid and encoding a putative protein with significant similarity to the
      helicase domain of viral and plasmid primase proteins, as well as to the newly
      described archaeal primase-polymerase domain. A small ORF, (ORF80), located
      upstream of this putative polymerase, encodes a putative copy number control
      protein. Specific transcripts corresponding to the ORF80 and ORF915, were
      detected by Northern blot analyses, and their transcriptional start sites were
      determined by primer extension. Moreover, the transfer and the maintenance of the
      plasmid in other Sulfolobus strains were demonstrated to be effective and stable.

PMID- 16624406
TI  - Marsupial development in the mysid Neomysis integer (Crustacea: Mysidacea) to
      evaluate the effects of endocrine-disrupting chemicals.
AB  - Embryonic development is a crucial time window within an organism's life history.
      Relatively few studies have focused on understanding the potential effects of
      endocrine disruptors on embryogenesis in invertebrates. Mysids (Crustacea:
      Mysidacea) have been used extensively in regulatory toxicity testing and they are
      the only invertebrate model currently included in the U.S. EPA's Endocrine
      Disruptor Screening and Testing Program. We developed a method for studying mysid
      embryonic development in multiwell plates until the release of free-swimming
      juveniles. This method was used to evaluate the potential effects of the
      insecticide methoprene, a juvenile hormone analog, on mysid embryogenesis.
      Embryos were exposed to nominal concentrations 0.01, 1, and 100 microg
      methoprene/L. Average percentage survival, hatching success, total development
      time and duration of each developmental stage were analyzed. Embryos exposed to 1
      and 100 microg methoprene/L had a significantly lower hatching success and lower
      survival rates. Our study indicates that in vitro embryogenesis can be used as a
      valuable tool to study the impact of endocrine disruptors in mysids.

PMID- 16624407
TI  - Histopathological and immunohistochemical findings in lymphoid tissues of the
      endangered Iberian lynx (Lynx pardinus).
AB  - The Iberian lynx (Lynx pardinus) is the most threatened wild feline in the world.
      Little is known about the diseases and pathology that affect this animal. The aim
      of this study was to evaluate the histopathological status of the peripheral
      lymphoid tissues and thymus of Iberian lynxes necropsied between 1998 and 2003.
      Seventeen animals including females (n=8) and males (n=9), age range of 10 months
      to 16 years, with different causes of death were histopathologically and
      immunohistochemically (anti-CD3, CD79, MAC387, CD68) studied. Feline
      immunosuppressive virus laboratorial tests were negative. Five individuals
      presented neoplasia and/or tuberculosis. All animals presented some degree of
      both B and T cells depletion in peripheral lymphoid tissues and follicular
      hyalinosis in the center of depleted follicles. A viral origin of the lymphoid
      depletion is postulated although other causes (inbreeding, stress, toxic) are not
      ruled out. The loss of the effectiveness of the immune system increases the
      vulnerability of the critically endangered Iberian lynx to pathogens.

PMID- 16624409
TI  - Life cycle assessment of second generation (2G) and third generation (3G) mobile
      phone networks.
AB  - The environmental performance of presently operated GSM and UMTS networks was
      analysed concentrating on the environmental effects of the End-of-Life (EOL)
      phase using the Life Cycle Assessment (LCA) method. The study was performed based
      on comprehensive life cycle inventory and life cycle modelling. The environmental
      effects were quantified using the IMPACT2002+ method. Based on technological
      forecasts, the environmental effects of forthcoming mobile telephone networks
      were approximated. The results indicate that a parallel operation of GSM and UMTS
      networks is environmentally detrimental and the transition phase should be kept
      as short as possible. The use phase (i.e. the operation) of the radio network
      components account for a large fraction of the total environmental impact. In
      particular, there is a need to lower the energy consumption of those network
      components. Seen in relation to each other, UMTS networks provide an
      environmentally more efficient mobile communication technology than GSM networks.
      In assessing the EOL phase, recycling the electronic scrap of mobile phone
      networks was shown to have clear environmental benefits. Under the present
      conditions, material recycling could help lower the environmental impact of the
      production phase by up to 50%.

PMID- 16624408
TI  - Measurement of estrogenic activity in sediments from Haihe and Dagu River, China.
AB  - Sediments from two rivers in China, the Haihe and Dagu Rivers, were examined for
      estrogenic activity using an estrogen receptor (ER)-mediated in vitro bioassay
      system. ER-active compounds were isolated from sediments by Soxhlet extraction,
      and the crude extracts were fractionated using a florisil column into three
      fractions. The estrogenic activity of each extract was detected by measuring
      luciferase activity in the human breast cancer cell line MCF-7 transfected with a
      luciferase receptor gene. Significant estrogenic activity was observed in each
      total extract. The 17beta-estradiol equivalents (E2-EQs) ranged from 8.24 to
      95.28 ng E2 g(-1) dw. As a result, the relative estrogenic potencies of three
      fractions in this study descended in the order of Fraction 3>Fraction 2>Fraction
      1. The results of the bioassay analysis indicated the heavy pollution status of
      these sites with estrogenic contaminants. In this study, five selected chemicals,
      the natural estrogens 17beta-estradiol (E2) and estrone (E1), and the xeno
      estrogens 4-octylphenol (OP), 4-nonylphenol (NP), and Bisphenol A (BPA) were also
      analyzed using the in vitro bioassay. The estrogenic activity of these chemicals
      were E2>E1>NP>OP>BPA.

PMID- 16624410
TI  - Determination of endocrine disruptors in Kafue lechwe (Kobus leche kafuensis)
      samples from the Lochinvar National Park of Zambia.
AB  - Analysis of serum, whole blood and liver tissue samples from Kafue lechwe in the
      Lochinvar National Park of Zambia for suspected endocrine disrupting compounds
      revealed high concentrations for some of the compounds. 45 samples of serum,
      whole blood and liver tissue were extracted by liquid-liquid extraction followed
      by an analysis using Gas Chromatography-Electron Capture Detection (GC-ECD). The
      following endocrine disruptors were analyzed: deltamethrin, aldrin, endosulfan,
      dieldrin, pp-DDD, heptachlor, d-t-allethrin, pp-DDE, endrin and pp-DDT. For all
      the samples, dieldrin showed the highest concentration ranging from 1.7 to 44.4
      microg/ml in serum and whole blood sample extracts and 0.10-5.1 microg/g wet
      weight in liver sample extracts. The most frequently detected was deltamethrin in
      62% of the samples. Percent recoveries in spiked laboratory blanks ranged between
      60% and 100% while calculated detection limits ranged from 0.004 to 0.21
      microg/ml for all the endocrine disruptors evaluated. Where endocrine disruptors
      were detected, the concentrations of most of them far exceeded the maximum
      residue limits (MRLs) and the extraneous maximum residue limits (EMRLs) set by
      the Codex Alimentarius of the United Nations (UN), Food and Agricultural
      Organization (FAO).

PMID- 16624411
TI  - Incorporation of human complement C8 into the membrane attack complex is mediated
      by a binding site located within the C8beta MACPF domain.
AB  - Human C8 is one of five complement components (C5b, C6, C7, C8, C9) that interact
      to form the membrane attack complex (MAC). C8 is an oligomeric protein composed
      of a disulfide-linked C8alpha-gamma heterodimer and a noncovalently associated
      C8beta chain. C8alpha and C8beta are homologous; both contain N- and C-terminal
      modules and an intervening approximately 40 kDa segment referred to as the
      membrane attack complex/perforin (MACPF) domain. C8beta participates in at least
      two binding interactions. It has a high affinity binding site for C8alpha, which
      facilitates its interaction with C8alpha-gamma. C8beta also mediates
      incorporation of C8 into the MAC by binding to C5b-7, an intermediate in the MAC
      assembly pathway. Little is known about the location or properties of the
      respective binding sites on C8beta. In this study, the MACPF domain of C8beta
      (betaMACPF) was expressed in Escherichia coli and its role in binding C8alpha and
      C5b-7 examined. Recombinant betaMACPF was shown to bind C8alpha-gamma in solution
      and form a noncovalent complex (betaMACPF*C8alpha-gamma) that exhibited C8
      hemolytic activity. betaMACPF was also capable of binding independently to
      erythrocytes carrying C5b-7. Subsequent addition of C8alpha-gamma and C9 to these
      cells produced a hemolytically active MAC. The ability to produce a soluble,
      recombinant betaMACPF that retains the binding functions of C8beta suggests this
      segment of C8beta is an independently folded domain. Furthermore, results
      indicate the principal binding sites for C8alpha and C5b-7 are located within
      this domain, and that C8beta binding specificity is not determined by the N- and
      C-terminal modules.

PMID- 16624412
TI  - Ligand binding properties of two kinds of reconstituted myoglobins with iron
      porphycene having propionates: effect of beta-pyrrolic position of two propionate
      side chains in porphycene framework.
AB  - An iron porphycene containing two propionate side chains at the 12th and 17th
      beta-pyrrolic positions of the porphycene ring was synthesized and incorporated
      into sperm whale apomyoglobin in order to investigate the O(2) and CO binding
      properties of the reconstituted ferrous myoglobin. The protein showed a slower
      O(2) dissociation rate by 1/20, compared to the native myoglobin, whereas the CO
      dissociation rates were found to be almost the same. This tendency is similar to
      the result of a previous study on the reconstituted myoglobin with a porphycene
      having the propionates at the 13th and 16th beta-pyrrolic positions. However, the
      present myoglobin showed a faster O(2) dissociation than the previously studied
      myoglobin. This finding suggests that the position of the two propionates as well
      as the symmetry of the porphycene framework is an important factor for obtaining
      a stable oxygenated iron porphycene myoglobin.

PMID- 16624413
TI  - (Dien)M(II) (M=Pd, Pt) and (NH3)3Pt(II) complexes of 1-methylcytosine: Linkage
      and rotational isomerism, metal-promoted deamination, and pathways to dinuclear
      species.
AB  - Despite their structural similarity, [Pt(dien)(1-MeC-N3)](2+) (1), [Pd(dien)(1
      MeC-N3)](2+) (2), and [Pt(NH(3))(3)(1-MeC-N3)](2+) (3) (with
      dien=diethylenetriamine and 1-MeC=neutral 1-methylcytosine) behave in part
      markedly different at strongly alkaline pH (12-13) and at room temperature. While
      1 and 2, yet not 3 show linkage isomerization from N3 to N4, deamination of the
      cytosine nucleobase to 1-methyluracilate occurs with 1 and 3, yet not with 2.
      Pathways leading to N3,N4-diplatinated 1-MeC(-) complexes (1-MeC(-)=1
      methylcytosine, deprotonated at exocyclic amino group N4) have been studied at
      high pH by starting from 1 and 3, respectively, and adding (dien)Pt(II). It
      appears that initial migration of the metal entity from N3 to N4, followed by
      binding of the second metal to the available N3 site, is favored over sequential
      coordination to N3 and then N4. X-ray crystal data of 1-3 density functional
      theory (DFT) calculations, and NMR ((1)H, (195)Pt) data are presented.

PMID- 16624414
TI  - XANES investigation of the Co oxidation state in solution and in cancer cells
      treated with Co(III) complexes.
AB  - XANES spectroscopy has been used to investigate whether it is possible to
      determine the oxidation state and coordination environment of Co complexes
      following treatment of cancer cells with Co(III) or Co(II) complexes. Our results
      show that the variation of the XANES with coordination geometry make it
      impossible to do this in a completely reliable way which is in contrast to the
      situation for platinum and chromium. It was established that the XANES spectrum
      obtained from cells treated with [Co(diNOsar)]Br(3) remained unchanged with
      respect to its XANES spectrum obtained in solution, demonstrating that the
      [Co(diNOsar)]Br(3) complex remained intact after 24h in cellular media
      (diNOsar=1,8-dinitro-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane). In contrast,
      the XANES spectra obtained from cells treated with Na[Co(acac)(3)] and
      [Co(acac)(3)] differed from the XANES spectra of the respective complexes
      obtained in solution, indicating a change in co-ordination environment for both
      complexes upon uptake in cells. The similarity of these spectra suggests that
      appearance of this XANES can be used as an indication of loss of the carrier
      ligands, a useful indicator in the study of hypoxia selective complexes. The
      results obtained for Na[Co(acac)(3)] and [Co(acac)(3)] are consistent with the
      intracellular coordination of cobalt(III) to sulfur ligands upon cellular uptake.

PMID- 16624415
TI  - The role of radical reactions in organomercurials impact on lipid peroxidation.
AB  - The organomercury compounds RHgX and R(2)Hg are broad-spectrum biocidal agents
      acting via diverse mechanisms in biological systems. Despite the enormous amount
      of studies carried out in last decades to elucidate the detailed mechanisms of
      organomercurials toxicity their biomolecular mode of action is still under
      debate. Among various toxicity mechanisms the action of RHgX and R(2)Hg at the
      membrane level due to the lipophilic properties of their molecules is discussed.
      Organomercurials are supposed to induce membrane associated oxidative stress in
      living organism through different mechanisms including the enhancement of the
      lipid peroxidation and intracellular generation of reactive oxygen species (ROS),
      H(2)O(2), O(2)(-), HO(). The perturbation of antioxidative defense system and the
      peroxidation of unsaturated fatty acids in membrane lipid bilayer are
      consequences of this impact. On the other hand, the involvement of
      organomercurials in radical and redox biochemical processes is manifested in
      carbon to metal bond cleavage that leads to the generation of reactive organic
      radicals R(). This pathway is discussed as one of the multiple mechanisms of
      organomercurials toxicity. The goal of this review is to present recent results
      in the studies oriented towards the role of organomercurials in the xenobiotic
      mediated enhancement of radical production and hence in the promotion of lipids
      peroxidation. The application of natural and synthetic antioxidants as
      detoxification agents is presented.

PMID- 16624416
TI  - The enzymatic activity from the sediment of the Gilau dam reservoir - Cluj
      county.
AB  - The enzymological studies on the sediment of the accumulation lake that has the
      main purpose of supplying drinking water to the city of Cluj-Napoca and the
      nearby villages, were aimed at the comprehensive understanding of the complex
      processes that happen in these habitats of special significance. In the sediment
      samples the following enzymatic activities have been quantitatively determined:
      phosphatase, actual and potential dehydrogenase, catalase, urease and protease.
      Non-enzymatic catalytic activity was also measured. Based on the relative values
      for the enzymatic activities, the enzymatic indicator of the sediment quality
      (EISQ) was calculated (ranging from 0.1 to 0.7). The enzymatic activities have
      been qualitatively determined for maltase, saccharase, lactase, cellobiase,
      amylase, dextranase, levanase, cellulase and inulinase. The correlation between
      the enzymatic and bacteriologic potential was statistically calculated.

PMID- 16624417
TI  - Three generations of alpha,gamma-diaminobutyric acid modified
      poly(propyleneimine) dendrimers and their cisplatin-type platinum complexes.
AB  - Three generations of alpha,gamma-diaminobutyric acid modified
      poly(propyleneimine) dendrimers [DAB(AM)n, n = 4, 8, 16] containing 4, 8, 16 free
      amino groups were coupled with Boc-protected alpha,gamma-diaminobutyric acid
      (DABA) moieties in high yields. These modified dendrimers were deprotected and
      the chiral dendritic amines with 8, 16 and 32 amino groups on the surface were
      isolated in excellent yields. Dendrimers with cisplatin moieties at the periphery
      were obtained in the reaction of the free amine dendrimers and potassium
      tetrachloroplatinate(II). The highly insoluble complexes were isolated as
      hydrates and characterized by means of IR, TGA and elemental analysis.

PMID- 16624418
TI  - Analysis of the vibrational spectra of new OH-containing E-4-arylmethylene-3
      isochromanones and 3-arylcoumarins.
AB  - A combined experimental and theoretical approach is presented to structural
      characterization of fairly large, newly synthesized organic molecules in order to
      enhance the effectiveness of their instrumental analysis by vibrational
      spectroscopy. The method consists of measurement of FT-IR and Raman spectra of
      the reaction products and subsequent ab initio or DFT quantum mechanical
      calculations (prediction) of the vibrational spectra for any anticipated
      structural varieties of the synthesized molecules. Comparison of the measured and
      computed frequencies as well as the observed and simulated spectra is performed
      to resolve any uncertainties in identifying the reaction products. Vibrational
      frequency and normal mode calculations based on scaled quantum mechanical (SQM)
      force fields performed at the DFT/B3LYP/6-31G* level of theory are demonstrated
      to provide a wealth of information that have been used in this work to ascertain
      the molecular structure, probable conformation and H-bond properties of three new
      isochromanone or coumarin derivatives, namely: 3-([2'-hydroxymethyl]-phenyl)
      coumarin (1), E-4-(3'-hydroxyphenylmethylene)-3-isochromanone (2), and 2-[(2'
      hydroxymethyl)phenyl]-3H-naphto[2,1-b]pyran-3-one (3).

PMID- 16624419
TI  - New model substrates for enzymes hydrolysing polyethyleneterephthalate and
      polyamide fibres.
AB  - Recently the potential of enzymes for surface hydrophilisation and/or
      functionalisation of polyethyleneterephthalate (PET) and polyamide (PA) has been
      discovered. However, there was no correlation between enzyme class/activity (e.g.
      esterase, lipase, cutinase) and surface hydrolysis of these polymers and
      consequently no simple assay to estimate this capability. Enzymes active on the
      model substrates bis (benzoyloxyethyl) terephthalate and adipic acid bishexyl
      amide, were also capable of increasing the hydrophilicity of PET and PA. When
      dosed at the identical activity on 4-nitrophenyl butyrate, only enzymes from
      Thermobifida fusca, Aspergillus sp., Beauveria sp. and commercial enzymes
      (TEXAZYME PES sp5 and Lipase PS) increased the hydrophilicity of PET fibres while
      other esterases and lipases did not show any effect. Activity on PET correlated
      with the activity on the model substrate. Hydrophilicity of fibres was greatly
      improved based on increases in rising height of up to 4.3 cm and the relative
      decrease of water absorption time between control and sample of the water was up
      to 76%. Similarly, enzymes increasing the hydrophilicity of PA fibres such as
      from Nocardia sp., Beauveria sp. and F. solani hydrolysed the model substrate;
      however, there was no common enzyme activity (e.g. protease, esterase, amidase)
      which could be attributed to all these enzymes.

PMID- 16624420
TI  - Cocaine Craving Questionnaire: assessing craving among cocaine users in Brazil.
AB  - The Cocaine Craving Questionnaire was administered to 205 cocaine addicts. A 6/5
      cut-off corresponded to the scale's best performance. Reliability was 0.803.
      Receiver Operating Characteristic analysis resulted in an area under the curve of
      0.7199 +/- 0.0384, and dimensionality resulted in a three-factor solution. The
      scale is a reliable and valid instrument in identifying craving.

PMID- 16624421
TI  - Discrepancies of NKT cells expression in peripheral blood and in cerebrospinal
      fluid from Behcet's disease.
AB  - The precise role of natural killer T (NKT) cells in the pathogenesis of Behcet's
      disease (BD) remains unknown. The frequency, cytokine profile and heterogeneity
      of NKT cells were studied in peripheral blood mononuclear cells (PBMC) from 42BD
      patients and in cerebrospinal fluid (CSF) samples from 9 neuro-BD patients. Flow
      cytometry revealed a decreased frequency of NKT cells in PBMC from BD patients
      (median: 0.06%; range: 0%-0.3%) when compared to healthy controls (median: 0.23%;
      range: 0.1%-0.7%; P<0.01). NKT cells were biased toward a Th(1)-like phenotype,
      with a significant decrease of IL-4/IFN-gamma ratio in BD (median: 0.049; range:
      0.01-0.13) vs. healthy controls (median: 0.82; range: 0.4-1.33; P<0.01). NKT
      cells were increased in CSF-BD samples (median: 0.18%; range: 0.1%-0.4%), when
      compared to CSF-NIND patients (median: 0.05%; range: 0.01%-0.09%; P<0.01). Based
      on the reactivity of PBMC-derived NKT cells toward alpha-galactosylceramide
      (alpha-GalCer), 80% of BD patients were non-responsive. At the opposite, the
      reactivity of NKT cells in CSF from BD patients was not impaired. BD-CSF NKT
      cells exhibited an increased expression of IFN-gamma-producing cells,
      demonstrating that CSF-NKT cells were functional, and biased toward a Th(1)-like
      phenotype. These data suggest that functional NKT cells are recruited into BD
      inflammatory sites contributing to BD pathogenesis.

PMID- 16624422
TI  - Cognitive flexibility but not cognitive coordination is affected in rats with
      toxic liver failure.
AB  - Hepatic encephalopathy (HE), a consequence of liver damage, is associated with
      cognitive deficits. In this study, behavioral activity, non-associative learning,
      associative memory, cognitive coordination and flexibility were investigated in
      rats with subclinical HE evoked by thioacetamide treatment. Non-associative
      learning was studied in the open field (OF) set up in 12 HE and 8 saline-injected
      control rats (C). Memory was examined in spatial place avoidance tasks in 10 HE
      and 10 C rats. The Room+ Arena- task involved the selection of distal room
      stimuli from irrelevant arena stimuli (i.e. intramaze cues and/or self-motion
      information), which engages processes of cognitive coordination. Following the
      Room+ Arena- training, cognitive flexibility of rats was tested in the Arena+
      place avoidance condition, which demands the previously ignored stimuli from
      arena. In the OF test HE and control rats behaved similar. They displayed high
      activity in the first block of each session and this pattern was stable. In both
      groups of rats darkness enhanced locomotor activity in comparison to light only
      in the first block. The HE and C rats avoided the to-be-avoided place in the
      Room+ Arena- task, whereas only HE rats were affected in the Arena+ task. In
      conclusion, these results demonstrate cognitive inflexibility in HE rats. We
      suggest that (1) the behavioral changes in the TAA model are typical of
      subclinical HE and (2) test for cognitive flexibility may be modified towards a
      routine use in patients with subclinical HE.

PMID- 16624423
TI  - Behavioural responses of Gammarus pulex (Crustacea, Amphipoda) to low
      concentrations of pharmaceuticals.
AB  - The continuous discharge of pharmaceuticals and personal care products into the
      environment results in a chronic exposure of aquatic organisms to these
      substances and their metabolites. As concentrations in surface waters are in the
      ng/L range, and sometimes in the low microg/L range, they are not likely to
      result in lethal toxicity. However, prolonged exposure to low concentrations of
      anthropogenic chemicals may lead to sublethal effects, including changes in
      behaviour. The aim of this study was to assess the effect of three
      pharmaceuticals, the antidepressant fluoxetine, the analgesic ibuprofen and the
      anti-epileptic carbamazepine, and one cationic surfactant, cetyltrimethylammonium
      bromide (CTAB), on the activity of the benthic invertebrate Gammarus pulex
      (Crustacea: Amphipoda: Gammaridae). We used the multispecies freshwater
      biomonitor to assess changes in activity of G. pulex in a quantitative manner.
      Exposure to low concentrations (10-100ng/L) of fluoxetine and ibuprofen resulted
      in a significant decrease in activity, whereas the activity of G. pulex at higher
      concentrations (1microg/L-1mg/L) was similar to the control. Response to
      carbamazepine showed a similar pattern, however, differences were not
      significant. The tested surfactant CTAB evoked a decrease in activity at
      increasing concentration. These behavioural effect concentrations were 10(4) to
      10(7) times lower than previously reported LOECs and in the range of
      environmentally occurring concentrations. The potential consequences of this
      decreased activity for G. pulex population growth and benthic community structure
      and the exposure to mixtures of pharmaceuticals deserves further attention.

PMID- 16624424
TI  - Expression and cellular localization of dbpC/Contrin in germ cell tumor cell
      lines.
AB  - The transcriptional regulation of the germ cell-specific cold-shock domain
      protein dbpC/Contrin was investigated, and the promoter region between -272 and 
      253 relative to the transcription start site was shown to be critical for the
      manifestation of cell-type specific transcription. In vivo footprint analysis
      demonstrated that the E-box located between -272 and -253 is protected in the
      dbpC/Contrin-positive germ cell tumor cell lines NEC8 and TERA1, but not in the
      dbpC/Contrin-negative bladder cancer cell line T24 or ovarian cancer cell line
      A2780. The promoter activity of the dbpC/Contrin gene was transactivated by co
      transfection with c-Myc and the N-Myc expression plasmid. Western blotting
      analysis clearly showed that N-Myc is highly expressed in both NEC8 and TERA1
      cells, and that c-Myc is expressed in both T24 and A2780 cells. These data
      demonstrate that cell-type specific dbpC/Contrin expression in germ cells is
      regulated by N-Myc. In addition, dbpC/Contrin is localized mainly in the
      cytoplasm of NEC8 and TERA1 cells, but is translocated to the nucleus when its C
      terminal region is partially deleted. Our findings also suggest that dbpC/Contrin
      can be used as a molecular tool for the detection of germ cell tumors.

PMID- 16624425
TI  - eEF1B: At the dawn of the 21st century.
AB  - Translational regulation of gene expression in eukaryotes can rapidly and
      accurately control cell activity in response to stimuli or when rapidly dividing.
      There is increasing evidence for a key role of the elongation step in this
      process. Elongation factor-1 (eEF1), which is responsible for aminoacyl-tRNA
      transfer on the ribosome, is comprised of two entities: a G-protein named eEF1A
      and a nucleotide exchange factor, eEF1B. The multifunctional nature of eEF1A, as
      well as its oncogenic potential, is currently the subject of a number of studies.
      Until recently, less work has been done on eEF1B. This review describes the
      macromolecular complexity of eEF1B, its multiple phosphorylation sites and
      numerous cellular partners, which lead us to suggest an essential role for the
      factor in the control of gene expression, particularly during the cell cycle.

PMID- 16624426
TI  - Interactions of mitochondria with the actin cytoskeleton.
AB  - Interactions between mitochondria and the cytoskeleton are essential for normal
      mitochondrial morphology, motility and distribution. While microtubules and their
      motors have been established as important factors for mitochondrial transport,
      emerging evidence indicates that mitochondria interact with the actin
      cytoskeleton in many cell types. In certain fungi, such as the budding yeast and
      Aspergillus, or in plant cells mitochondrial motility is largely actin-based.
      Even in systems such as neurons, where microtubules are the primary means of long
      distance mitochondrial transport, the actin cytoskeleton is required for short
      distance mitochondrial movements and for immobilization of the organelle at the
      cell cortex. The actin cytoskeleton is also involved in the immobilization of
      mitochondria at the cortex in cultured tobacco cells and in budding yeast. While
      the exact nature of these immobilizations is not known, they may be important for
      retaining mitochondria at sites of high ATP utilization or at other cellular
      locations where they are needed. Recent findings also indicate that mutations in
      actin or actin-binding proteins can influence mitochondrial pathways leading to
      cell death. Thus, mitochondria-actin interactions contribute to apoptosis.

PMID- 16624427
TI  - Mitochondrial morphology and protein import--a tight connection?
AB  - Although the field of mitochondrial protein import and assembly may have
      initially been viewed as a completely distinct area of investigation to that of
      mitochondrial morphology and dynamics, recent findings have noted a clear
      influence on organelle morphology by perturbations in protein import pathways.
      This review aims to provide an overview of the mitochondrial import machinery in
      context of the recent link between translocation components and organelle
      structure, in addition to conferring the questions and challenges that have
      surfaced due to these observations.

PMID- 16624429
TI  - Multislice computed tomographic angiography of a spontaneous left internal
      mammary graft dissection.

PMID- 16624428
TI  - Mitochondrial dynamics and aging: Mitochondrial interaction preventing
      individuals from expression of respiratory deficiency caused by mutant mtDNA.
AB  - In mammalian cells, there is an extensive and continuous exchange of
      mitochondrial DNA (mtDNA) and its products between mitochondria. This
      mitochondrial complementation prevents individuals from expression of respiration
      deficiency caused by mutant mtDNAs. Thus, the presence of mitochondrial
      complementation does not support the generally accepted mitochondrial theory of
      aging, which proposes that accumulation of somatic mutations in mtDNA is
      responsible for age-associated mitochondrial dysfunction. Moreover, the presence
      of mitochondrial complementation enables gene therapy for mitochondrial diseases
      using nuclear transplantation of zygotes.

PMID- 16624430
TI  - An unusual cause of fatal pulmonary embolism.
AB  - We report on a case of a fatal pulmonary embolism--an unexpected finding at
      autopsy of a 71-year-old man who had suffered from severe erosive gouty
      arthritis. Using morphological findings, medical history and histopathological
      results, we show the potentially devastating complications of this fairly common
      medical condition, occurring as a result of massive bone marrow erosion and
      detachment and finally leading to embolization of the lungs.

PMID- 16624431
TI  - New acquisition method to exclusively enhance the left side of the heart by a
      small amount of contrast material achieved by multislice computed tomography with
      64 data acquisition system.
AB  - PURPOSE: To exclusively enhance the left side of the heart by a small amount of
      contrast material (CM) using rapid acquisition of multislice computed tomography
      (MSCT) with a 64-data acquisition system (DAS). MATERIALS AND METHODS: Forty
      consecutive subjects underwent MSCT (Light Speed VCT, GE) with 0.625mm slice
      thickness to evaluate coronary arteries. We first measured transit time, using
      8ml of CM followed by 20ml saline. Dependent upon transit time, total volume of
      CM was determined, ranging from 45 to 63ml. After injection of CM at a rate of
      4ml/s, followed by 47ml saline at 3.5ml/s, ECG-gated MSCT scanning was performed.
      The mean and standard deviation (S.D.) of CT values of the right atrium (RA),
      right ventricle (RV), left atrium (LA), left ventricle (LV), ascending aorta (Ao)
      and each coronary artery were measured. RESULTS: The mean of the CT values of the
      RA, RV, LA, LV, Ao, right coronary artery, left main, left anterior descending
      branch, and left circumflex branch were 225+/-76, 251+/-72, 353+/-55, 355+/-51,
      352+/-34, 312+/-65, 296+/-57, 285+/-55, and 267+/-60HU, respectively. The
      corresponding S.D.s of the CT values were 39+/-22, 37+/-16, 32+/-7, 31+/-8HU,
      25+/-5, 36+/-15, 31+/-13, 36+/-23, and 40+/-18HU, respectively. The mean of CT
      values of the RA and RV were significantly lower than those of the LA, LV, Ao,
      and each coronary artery (P<0.01), with excellent S.D.s. We could easily obtain
      three-dimensional coronary arterial and LV images without artifact of the RA and
      RV. CONCLUSIONS: Using 64-DAS MSCT, we successfully obtained exclusive
      enhancement of the left side of the heart using a small amount of CM.

PMID- 16624432
TI  - Training of interventional cardiologists in radiation protection--the IAEA's
      initiatives.
AB  - The International Atomic Energy Agency (IAEA) has initiated a major international
      initiative to train interventional cardiologists in radiation protection as a
      part of its International Action Plan on the radiological protection of patients.
      A simple programme of two days' training has been developed, covering possible
      and observed radiation effects among patients and staff, international standards,
      dose management techniques, examples of good and bad practice and examples
      indicating prevention of possible injuries as a result of good practice of
      radiation protection. The training material is freely available on CD from the
      IAEA. The IAEA has conducted two events in 2004 and 2005 and number of events are
      planned in 2006. The survey conducted among the cardiologists participating in
      these programmes indicates that over 80% of them were attending such a structured
      programme on radiation protection for the first time. As the magnitude of X-ray
      usage in cardiology grows to match that in interventional radiology, the
      standards of training on radiation effects, radiation physics and radiation
      protection in interventional cardiology should also match those in interventional
      radiology.

PMID- 16624433
TI  - Iso-osmolar contrast medium better preserves short- and long-term renal function
      after cardiovascular catheterizations in patients with severe baseline renal
      insufficiency.
AB  - BACKGROUND: Iso-osmolar iodixanol was shown to least affect very-short-term renal
      function. However, its short- and long-term renal effects after cardiovascular
      catheterizations in severe renal insufficiency remain unknown. METHODS: Patients
      undergoing elective cardiovascular catheterizations and having pre-procedural
      serum creatinine (Scr) > or =2.5 mg/dl were prospectively studied. The results
      were compared to those of historical controls who received iopromide. RESULTS:
      The iodixanol group included 27 patients, aged 73+/-1 years, and the case-matched
      control group consisted of another 27 patients, aged 71+/-1 years. The baseline
      Scr were 3.0+/-0.3 and 3.0+/-0.2 mg/dl respectively. Although the Scr at 3 months
      was similar, the Scr at 6 months was lower in the iodixanol group (2.7+/-0.3 vs
      4.2+/-0.5 mg/dl, p = 0.017). The absolute and percentage increments in Scr at 3
      months (0.0+/-0.2 vs 0.6+/-0.2 mg/dl, p = 0.014, and 1+/-4% vs 24+/-6%, p =
      0.003, respectively) and 6 months (-0.3+/-0.2 vs 1.3+/-0.4 mg/dl, p = 0.001, and 
      10+/-5% vs 47+/-12%, p < 0.001, respectively) were lower in the iodixanol group.
      CONCLUSIONS: Iodixanol better preserves short- and long-term renal outcomes in
      patients with severe baseline renal insufficiency.

PMID- 16624434
TI  - A left ventricular lipoma presenting as heart failure in a septuagenarian: a
      first case report.
AB  - A 78-year-old Caucasian female presented as an outpatient with a 6-month history
      of severe progressive exertional dyspnea interfering with ambulating at home.
      Physical Exam revealed signs of heart failure with laboratory studies being
      normal. A subsequent echocardiogram revealed a mass in the left ventricle and the
      patient underwent successful resection of the mass with complete resolution of
      her symptoms. Histologic examination was consistent with a benign lipoma. After a
      comprehensive PubMed literature, we believe to report the first case of a left
      ventricular lipoma diagnosed and treated in the eighth decade of life.

PMID- 16624435
TI  - 16S rRNA targeted sandwich hybridization method for direct quantification of
      mycobacteria in soils.
AB  - Boreal soils have been suspected reservoirs of infectious environmental
      mycobacteria. Detection of these bacteria in the environment is hampered by their
      slow growth. We applied a quantitative sandwich hybridization approach for direct
      detection of mycobacterial 16S rRNA in soil without a nucleic acid amplification
      step. The numbers of mycobacterial 16S rRNA molecules found in the soil indicated
      the presence of up to 10(7) to 10(8) mycobacterial cells per gram of soil. These
      numbers exceed by factor of 10 to 100 x the previous estimates of mycobacteria in
      soil based on culture methods. When real-time PCR with mycobacteria targeting
      primers was used to estimate the number of 16S rDNA copies in soil, one copy of
      16S rDNA was detected per 10(4) copies of 16S rRNA. This is close to the number
      of 16S rRNA molecules detected per cell by the same method in laboratory pure
      cultures of M. chlorophenolicum. Therefore a major part of the mycobacterial DNA
      in the studied soils may thus have represented metabolically active cells. The
      16S rRNA sandwich hybridization method described in this paper offers a culture
      independent solution for tracking environmental reservoirs of viable and
      potentially infectious mycobacteria.

PMID- 16624436
TI  - Green fluorescent protein is a reliable reporter for screening signal peptides
      functional in Lactobacillus reuteri.
AB  - A signal peptide (SP)-probe vector pNICE-gfpSP, which employed a green
      fluorescent protein (Gfp) as the SP-selection marker, was constructed for use in
      Lactobacillus reuteri. This chimerical plasmid allowed cloning and screening DNA
      fragments with the SP function by direct visualization of the expressed
      fluorescence activity around cells. Assay of fluorescent intensity in their
      culture supernatant with spectrofluorometry further enabled quantifying the
      secretion efficiency of the identified SP fragment.

PMID- 16624437
TI  - Biosurfactant MEL-A enhances cellular association and gene transfection by
      cationic liposome.
AB  - Mannnosylerythritol lipid A (MEL-A), a biosurfactant produced by microorganisms,
      has many biological activities. To enhance the gene transfection efficiency of a
      cationic liposome, we prepared a MEL-liposome (MEL-L) composed of 3beta-[N-(N',N'
      dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol), dioleoyl
      phosphatidylethanolamine (DOPE) and MEL-A, and investigated its transfection
      efficiency in human cervix carcinoma Hela cells. MEL-L was about 40 nm in size,
      and the MEL-L/plasmid DNA complex (MEL-lipoplex) remained an injectable size (169
      nm). MEL-A induced a significantly higher level of gene expression, compared to
      commercially available Tfx20 and the liposome without MEL-A (Cont-L). Analysis of
      flow cytometric profiles clearly indicated that the amount of DNA associated with
      the cells was rapidly increased and sustained by addition of MEL-A to the
      liposome. Confocal microscopic observation indicated that the MEL-lipoplex
      distributed widely in the cytoplasm, and the DNA was detected strongly in the
      cytoplasm and around the nucleus, compared with Cont-L. These results suggested
      that MEL-A increased gene expression by enhancing the association of the
      lipoplexes with the cells in serum. MEL-L might prove a remarkable non-viral
      vector for gene transfection and gene therapy.

PMID- 16624438
TI  - Correlations between measures of insulin sensitivity and weight loss.
AB  - OBJECTIVE: Many formulas have been proposed to calculate insulin sensitivity and
      studies have shown their effectiveness. However, few studies have been done to
      compare formulas. METHODS: Seventy-two obese participants completed a randomized
      weight loss study. Weight loss, change in body fat and change in waist
      circumference were used as surrogates for change in insulin sensitivity.
      Correlation coefficients were calculated for each of these surrogates with
      proposed formulas for insulin sensitivity found in the literature. RESULTS: The
      change in insulin sensitivity using the formula proposed by McAuley (exp(2.63
      0.28 x ln(fasting insulin)-0.31 x ln(fasting triglyceride in mmol/l)) showed the
      greatest correlation with weight loss (r=-0.59, p<0.0001) and was statistically
      superior to change in fasting glucose, fasting insulin and homeostasis model
      assessment (HOMA). CONCLUSIONS: The insulin sensitivity formula proposed by
      McAuley provides an accurate means of detecting insulin resistance. As it does
      not require a glucose tolerance test, it is also easier and less expensive than
      most other formulas. Use of this formula rather than fasting glucose would detect
      many more patients with insulin resistance who are at risk for subsequent
      diabetes and other complications.

PMID- 16624439
TI  - The role of polyol pathway in high glucose-induced endothelial cell damages.
AB  - To clarify the mechanism by which hyperglycemia in diabetes mellitus causes
      endothelial cell damages, the effects of high glucose on DNA fragmentation and
      caspase-3 activity of cultured endothelial cells and on the generation of 8
      hydroxy-2'-deoxyguanosine (8-OHdG) were studied. Furthermore, the involvement of
      the polyol pathway in this process was investigated using aldose reductase
      inhibitor (SNK-860). Human umbilical vein endothelial cells (HUVECs) were
      incubated with 5.5mmol/L (low glucose medium) or 28mmol/L (high glucose medium)
      of glucose. The amounts of fragmented DNA, caspase-3 activity and 8-OHdG in the
      medium increased in significantly greater extent in high glucose-incubated HUVECs
      than in low glucose-incubated HUVECs. No significant increase in fragmented DNA
      or 8-OHdG was observed when HUVECs were incubated with mannitol (500mg/mL). The
      concentration of intracellular sorbitol was significantly higher in HUVECs
      incubated in high glucose medium than that in low glucose medium. Addition of the
      aldose reductase inhibitor SNK-860 dose-dependently decreased the intracellular
      sorbitol concentration in HUVECs incubated in high glucose medium, and also
      significantly suppressed the increases in fragmented DNA, caspase-3 activity and
      8-OHdG by conditioning with high glucose medium. These results suggest that high
      glucose-induced endothelial cell damages may be mediated by activation of the
      polyol pathway accompanied by augmented oxidative stress.

PMID- 16624440
TI  - A behavioral model of clinician responses to incentives to improve quality.
AB  - The use of pay for performance (P4P) and public reporting of performance (PR) in
      health care is increasing rapidly worldwide. The rationale for P4P and PR comes
      from experience in other industries and from theories about incentive use from
      psychology, economics, and organizational behavior. This paper reviews the major
      themes from this prior research and considers how they might be applied to health
      care. The resulting conceptual model addresses the dual nature (combining direct
      financial and reputational incentives) of the initiatives many policymakers are
      pursuing. It also includes explicit recognition of the key contextual factors (at
      the levels of the markets and the provider organization) and provider and patient
      characteristics that can enhance or mitigate response to incentives. Evaluation
      of the existing literature (through June 2005) about incentive use in health care
      in light of the conceptual model highlights important weaknesses in the way that
      trials have been reported to date and suggests future research topics.

PMID- 16624441
TI  - Trends and future needs in clinical radiology: insights from an academic medical
      center.
AB  - OBJECTIVE: Advances in technology, expanding indications and defensive medical
      practice, in combination with population aging, have all contributed to a
      substantial increase in utilization of imaging and therapeutic radiology
      procedures in recent years. Moreover, the integration of education, innovation
      and research into high-volume workflow, although challenging, is a key
      requirement in teaching hospitals. Therefore, identifying forthcoming demand in
      the use of radiology services at a referral center might be of special interest
      and facilitate health policy planning in this context. METHODS: Data regarding
      conventional radiographic, ultrasonographic and computed tomography (CT)
      investigations, radiotherapy sessions, and interventional procedures were
      collected for a 5-year period (2000-2004). Based on these observations, we
      deployed appropriate models to forecast utilization rates in 2005-2009. RESULTS:
      Between 2000 and 2004, ultrasound examinations increased by 31.8%, mammography by
      31.6%, CT scans by 17.4%, interventions by 14.5% and radiotherapy sessions by
      13.9%, while conventional investigations decreased by 42.5%. We identified
      significant increasing trends for ultrasound, mammography, CT and interventions
      (all p<0.001 for linear component). Compared to current levels, the workload for
      these modalities is expected to rise in the next 5 years by 43%, 31%, 20% and
      14%, respectively. Radiotherapy sessions demonstrate an unstable, non-significant
      increasing trend (p=0.189), while utilization of conventional radiography
      declines rapidly (p<0.001 for linear trend, 5-year prediction -51%). CONCLUSIONS:
      In forthcoming years, the demand for radiology services at referral centers will
      increase substantially. Advances in digital technology alone will not suffice to
      completely alleviate the need for additional resources and well-trained
      personnel.

PMID- 16624442
TI  - A mountain-scale thermal-hydrologic model for simulating fluid flow and heat
      transfer in unsaturated fractured rock.
AB  - A multidimensional, mountain-scale, thermal-hydrologic (TH) numerical model is
      presented for investigating unsaturated flow behavior in response to decay heat
      from the proposed radioactive waste repository in the Yucca Mountain unsaturated
      zone (UZ), The model, consisting of both two-dimensional (2-D) and three
      dimensional (3-D) representations of the UZ repository system, is based on the
      current repository design, drift layout, thermal loading scenario, and estimated
      current and future climate conditions. This mountain-scale TH model evaluates the
      coupled TH processes related to mountain-scale UZ flow. It also simulates the
      impact of radioactive waste heat release on the natural hydrogeological system,
      including heat-driven processes occurring near and far away from the emplacement
      tunnels or drifts. The model simulates predict thermally perturbed liquid
      saturation, gas- and liquid-phase fluxes, and water and rock temperature
      elevations, as well as the changes in water flux driven by
      evaporation/condensation processes and drainage between drifts. These simulations
      provide insights into mountain-scale thermally perturbed flow fields under
      thermal loading conditions.

PMID- 16624443
TI  - Visualization of TCE recovery mechanisms using surfactant-polymer solutions in a
      two-dimensional heterogeneous sand model.
AB  - This research focused on the optimization of TCE dissolution in a physical two
      dimensional model providing a realistic representation of a heterogeneous
      granular aquifer. TCE was infiltrated in the sand pack where it resided both in
      pools and in zones of residual saturation. Surfactant was initially injected at
      low concentration to minimize TCE remobilization at first contact but was
      incrementally increased later during the experiment. Xanthan gum was added to the
      injected surfactant solution to optimize the sweep efficiency through the
      heterogeneous medium. Photographs and digital image analysis illustrated the
      interactions between TCE and the injected fluids. During the polymer flood, the
      effects of heterogeneities inside the sand pack were greatly reduced by the
      increased fluid viscosity and the shear-thinning effects of the polymer. The
      polymer also improved the contact between the TCE ganglia and the surfactant
      polymer solution, thereby promoting dissolution. Surfactants interacted with the
      polymer reducing the overall viscosity of the solution. At first contact with a
      0.5%(mass) surfactant solution, the TCE pools drained and some remobilization
      occurred. However, no TCE bank was formed and TCE did not penetrate into any
      previously uncontaminated areas. As a result, TCE surface area was increased.
      Subsequent surfactant floods at higher surfactant concentrations did not trigger
      more remobilization. TCE was mainly dissolved by the solution with the highest
      surfactant concentration. Plugging from bacterial growth or microgel formation
      associated to the polymer at the inflow screen prevented the full completion of
      the experiment. However, more than 90% of TCE was recovered with the circulation
      of less than 6 pore volumes of surfactant-polymer solution.

PMID- 16624444
TI  - Confirmatory factor analysis of the child-feeding questionnaire among parents of
      adolescents.
AB  - We investigated the validity of the child-feeding questionnaire (CFQ) among
      parents of adolescents. The original CFQ was developed to assess perceptions of
      obesity-proneness and child-feeding practices among parents of 2- to 11-year-old
      children. We modified the CFQ to make it applicable to parents of adolescents and
      added one item on monitoring sugared beverages. Confirmatory factor analysis was
      conducted using the latent variable approach. Factor scores were related to
      adolescent body mass index percentiles (BMI%) using structural equation modeling.
      The modified CFQ was completed by 260 parent/guardians (mean age 39.8 years; 92%
      female; 55% Black, 35% White, 10% Other). The original published measurement
      model was fit to our sample and yielded an acceptable fit (CFI = 0.95, TLI =
      0.93, RMSEA = 0.05). Adding the extra variables decreased the fit; however, minor
      modifications improved the fit without changing the factor structure (CFI = 0.95,
      TLI = 0.94, RMSEA = 0.05). Cronbach's alphas for the subscales ranged from 0.60
      to 0.88. The factors, parental perceptions of child weight, concern for child
      weight, monitoring and restriction were positively associated, and pressure to
      eat was inversely associated with adolescent BMI%. In conclusion, the
      psychometric properties of the modified CFQ tested among parents of a multi
      ethnic adolescent sample were similar to those of the original CFQ.

PMID- 16624445
TI  - Cognitive dietary restraint and cortisol: importance of pervasive concerns with
      appearance.
AB  - The purpose of this study was to elucidate the nature of the relationship between
      dietary restraint and physiological stress, by investigating which eating and
      body-related constructs are related to salivary cortisol and to perceived stress.
      Female undergraduates (N = 170) completed self-report measures on dietary
      restraint, appearance beliefs, body satisfaction variables, perceived stress, and
      eating self-efficacy. Participants also provided two saliva samples. The first
      sample was collected after awakening, and the second was collected 6-8 h later. A
      factor analysis was performed in order to reduce redundancy in the set of
      measures surrounding eating and body attitudes, which yielded three factors. The
      findings indicated that women with stronger beliefs about the importance of their
      appearance, as well as negative emotions and cognitions surrounding their body
      image, had higher levels of cortisol in the afternoon. These appearance and body
      related constructs were also associated with higher levels of perceived stress.
      However, perceived stress was not associated with salivary cortisol. There were
      no significant relationships between any of the eating or psychological variables
      and morning cortisol levels. These results suggest that dysfunctional cognitions
      surrounding appearance and body image significantly contribute to the
      relationship between dietary restraint and elevations in cortisol excretion.
      Implications for interventions and women's health are discussed.

PMID- 16624446
TI  - Habituation and recovery of salivation and motivated responding for food in
      children.
AB  - Salivary responses habituate to repeated presentations of food cues, and these
      responses recover when new food stimuli are presented. Research suggests that
      within-session changes in motivated responding for food may also habituate, and
      motivated responding may, therefore, recover when new foods are presented. The
      purpose of this study was to evaluate similarities in the pattern of salivation
      and motivated responding for a cheeseburger stimulus in children, followed by
      either a novel stimulus (French fries) or another cheeseburger trial. The order
      of the task (salivation or motivation) was counterbalanced over days. Salivation
      and motivated responding for cheeseburger were reliably reduced over seven
      trials, and responses recovered after presentation of French fries on trial 8.
      Random regression models showed a significant relationship between the rate of
      change in motivated responding and salivation. These results provide additional
      support for similarities in processes that regulate salivation and motivated
      responding for food and strengthen support for the hypothesis that changes in
      motivated responding can be understood by habituation theory.

PMID- 16624447
TI  - Isolation and characterization of a novel glutathione S-transferase-activating
      peptide from the oriental medicinal plant Phellodendron amurense.
AB  - The aim of this study was to elucidate the characteristics of glutathione S
      transferase (GST)-activating compounds from medicinal plants. Among 265 kinds of
      medicinal plants, Phellodendron amurense showed the highest GST activity at
      174.8%. The GST-activating compound of P. amurense was maximally extracted when
      treated with distilled water at 30 degrees C for 12 h. The compound was purified
      by ultrafiltration, Sephadex G-10 gel filtration chromatography, and reverse
      phase HPLC. The purified GST-activating compound from P. amurense was a novel
      tetrapeptide with an amino acid sequence of Ala-Pro-Trp-Cys and its molecular
      weight was estimated to be 476 Da. It also displayed a clear detoxicative effect
      in 1-chloro-2,4-dinitrobenzene treated mice at a dosage of mg/kg body weight.

PMID- 16624448
TI  - Therapeutic window of bradykinin B2 receptor inhibition after focal cerebral
      ischemia in rats.
AB  - Following cerebral ischemia bradykinin/kinin B(2) receptors mediate inflammatory
      responses resulting in edema formation and secondary brain damage. However, the
      therapeutic window for B(2) receptor inhibition determining its potential
      clinical use has not been investigated so far. The aim of the current study was
      therefore to investigate the effect of delayed B(2) receptor inhibition on
      morphological and functional outcome following experimental stroke. Rats were
      subjected to 90 min of middle cerebral artery occlusion (MCAo) by an intraluminal
      filament. Animals received 0.9% NaCl or 1.0mg/kg/day Anatibant (LF 16-0687 Ms), a
      selective bradykinin B(2) receptor antagonist, for 3 days beginning at different
      time points after MCAo: 1, 2.5, 4.5, or 6.5h (n=10 per group). Neurological
      recovery was examined daily, infarct volume on day 7 after MCAo. Animal
      physiology was not influenced by B(2) receptor inhibition. Significant
      improvement of functional outcome was observed when treatment was delayed up to
      4.5h after ischemia (p<0.05 versus vehicle). Inhibition of B(2) receptors during
      ischemia, i.e. when the inhibitor was given 1h after MCAo, reduced infarct volume
      in the basal ganglia and in the cortex by 49% (p<0.05) and 26% (p<0.05),
      respectively. Inhibition of B(2) receptors at later time points (2.5, 4.5, or 6.5
      after MCAo) reduced penumbral damage, i.e. cortical infarction, by 19-26%
      (p<0.05). In conclusion, the current study shows that the therapeutic window of
      B(2) receptor inhibition extends for up to 6.5h after MCAo. Our data therefore
      suggest that inhibition of kinin B(2) receptors represents a treatment strategy
      for ischemic stroke which may warrant clinical validation.

PMID- 16624449
TI  - Oxidative stress: a bridge between Down's syndrome and Alzheimer's disease.
AB  - Besides the genetic, biochemical and neuropathological analogies between Down's
      syndrome (DS) and Alzheimer's disease (AD), there is ample evidence of the
      involvement of oxidative stress (OS) in the pathogenesis of both disorders. The
      present paper reviews the publications on DS and AD in the past 10 years in light
      of the "gene dosage" and "two-hit" hypotheses, with regard to the alterations
      caused by OS in both the central nervous system and the periphery, and the main
      pipeline of antioxidant therapeutic strategies. OS occurs decades prior to the
      signature pathology and manifests as lipid, protein and DNA oxidation, and
      mitochondrial abnormalities. In clinical settings, the assessment of OS has
      traditionally been hampered by the use of assays that suffer from inherent
      problems related to specificity and/or sensitivity, which explains some of the
      conflicting results presented in this work. For DS, no scientifically proven diet
      or drug is yet available, and AD trials have not provided a satisfactory approach
      for the prevention of and therapy against OS, although most of them still need
      evidence-based confirmation. In the future, a balanced up-regulation of
      endogenous antioxidants, together with multiple exogenous antioxidant
      supplementation, may be expected to be one of the most promising treatment
      methods.

PMID- 16624450
TI  - Supporting pre-registration students in practice: A review of current ICT use.
AB  - It is unclear how current healthcare students based in the United Kingdom (UK)
      use information and communication technology (ICT) to support their learning and
      care delivery in practice environments. This position reflects the dearth of
      current empirical evidence that needs development in this rapidly changing field.
      Using focus group interviews involving 16 students from nursing and the allied
      health professions, to reflect the interprofessional nature of healthcare
      education, this research explored how students employ technology in placement
      settings. The students drew on networked resources for personal learning and gave
      examples of use to meet patient and user needs. Technology also provided a
      vehicle for communication with the University, though use was complicated by a
      number of issues. Access to computers and the Internet whilst in placement
      environments proved problematic for some, with the culture not seeming to support
      ICT use. Lack of time, attitudes towards computers and ICT skills also affected
      student engagement. These findings provide information to guide the development
      of ICT use in placement settings.

PMID- 16624451
TI  - The disclosure of dyslexia in clinical practice: experiences of student nurses in
      the United Kingdom.
AB  - Heightened awareness and increasingly sophisticated psychological tests have seen
      a dramatic rise in the numbers of people diagnosed with dyslexia. Accordingly,
      there is a reported increase in the numbers of students with dyslexia entering
      Higher Education (HE) in the United Kingdom (UK) [Singleton, C.H., Chair, 1999.
      Dyslexia in higher education: policy, provision and practice. Report of the
      national working party on dyslexia in higher education. University of Hull on
      behalf of the Higher Education Funding Councils of England and Scotland, Hull],
      [Higher Education Statistics Agency. HESA. Available from: <URL
      http://www.hesa.ac.uk> (accessed 21.12.05)]. Studies researching the effects of
      dyslexia on the clinical practice of nurses are almost non-existent. This paper
      reports part of a UK study exploring the clinical experiences of student nurses
      with dyslexia. In depth interviewing of 18 adult branch student nurses revealed a
      range of difficulties encountered and a variety of coping mechanisms to manage
      these. Other than in exceptional circumstances there is no legal requirement to
      disclose a dyslexia diagnosis. The decision to conceal or disclose their dyslexia
      was particularly prominent and contentious for these participants. This related
      to the attitudes of co-workers, concerns for patient safety, expectations of
      support, confidentiality issues and potential discrimination. Dyslexia continues
      to attract an unwarranted stigma and can adversely affect the learning
      experience. The need for disability awareness training in the workplace and
      improved education/service partnerships to support these students is considered
      crucial.

PMID- 16624452
TI  - Situated cognition and cognitive apprenticeship: a model for teaching and
      learning clinical skills in a technologically rich and authentic learning
      environment.
AB  - The acquisition of a range of diverse clinical skills is a central feature of the
      pre-registration nursing curriculum. Prior to exposure to clinical practice, it
      is essential that learners have the opportunity to practise and develop such
      skills in a safe and controlled environment under the direction and supervision
      of clinical experts. However, the competing demands of the HE nursing curriculum
      coupled with an increased number of learners have resulted in a reduced emphasis
      on traditional apprenticeship learning. This paper presents an alternative model
      for clinical skills teaching that draws upon the principles of cognitive
      apprenticeship [Collins, A., Brown, J.S., Newman, S., 1989. Cognitive
      Apprenticeship: teaching the crafts of reading, writing and mathematics. In:
      Resnick, L.B. (Ed.) Knowing. Learning and Instruction: Essays in Honor of Robert
      Glaser. Lawrence Erlbaum Associates, New Jersey, pp. 453-494] and situated
      cognition within a technologically rich and authentic learning environment. It
      will show how high quality DVD materials illustrating clinical skills performed
      by expert practitioners have been produced and used in conjunction with CCTV and
      digital recording technologies to support learning within a pedagogic framework
      appropriate to skills acquisition. It is argued that this model not only better
      prepares the student for the time they will spend in the practice setting, but
      also lays the foundation for the development of a clinically competent
      practitioner with the requisite physical and cognitive skills who is fit for
      purpose [UKCC, 1999. Fitness for Practice: The UKCC Commission for Nursing and
      Midwifery Education. United Kingdom Central Council for Nursing Midwifery and
      Health Visiting, London].

PMID- 16624453
TI  - Issues in practice based learning in nursing in the United Kingdom and the
      Republic of Ireland: Results from a multi professional scoping exercise.
AB  - The first year (2003-2004) of a three year nationally funded project focused on
      completing a scoping exercise on the nature of practice education in five
      selected health care professions: Dietetics, Nursing, Occupational Therapy,
      Physiotherapy and Radiography (). A survey questionnaire, focus groups and
      secondary sources were used to collect data. Profession specific contributors
      completed the analysis of results. Resulting case studies were combined to
      produce a cross-professional overview of current issues in practice-based
      learning. The nursing case study identified areas of good practice such as; the
      mentorship model; the development of new support roles; and joint responsibility
      between Higher Education Institutes (HEIs) and Health Service areas for practice
      assessment. However, there were variations in the application of these areas of
      good practice throughout the United Kingdom (UK). Issues included; an inadequate
      supply of qualified mentors; formal recognition of the mentor role; and lack of
      knowledge of the relative impact of the differing mentor preparation programmes.
      In comparing the five professions, all had statutory requirements regarding the
      nature of practice learning but each profession differed in how this was managed
      and organised. The need for formal preparation, recognition and reward for the
      mentor/practice educator role was recognised with collaborative working across
      the professions a recommendation in order to achieve national improvement in the
      quality of practice learning support for health care professions.

PMID- 16624454
TI  - Entry criteria as predictor of performance in an undergraduate nursing degree
      programme.
AB  - The Nursing Council of New Zealand recently reviewed the minimum standard entry
      criteria for acceptance into undergraduate nursing programmes. The Otago
      Polytechnic School of Nursing in Dunedin felt it timely to explore the
      relationship between academic performance and entry criteria. The School's entry
      criteria included a bioscience requirement, which varied from the Nursing Council
      criteria. This research explored the relationship between entry criteria and
      academic performance in the first and second year bioscience papers. The sample
      consisted of 619 academic records of the 1994-2002 graduates from the Degree
      Programme. The sample was divided into an under 20-age group (n=323) and a 20 and
      over group (n=296). This division related to a difference in the entry criteria
      for each of the groups. Chi-square and correlational analyses found a
      relationship between entry qualifications and students' academic performance in
      the two papers. The entry criteria had a stronger relationship with the students'
      performance in the first year bioscience paper than the second year paper.
      Performance in the first year was predicative of second year performance. Age was
      also found to be a useful predictor of grades. These findings support the
      School's Bioscience entry criteria and provide important information for
      admission committees.

PMID- 16624455
TI  - Student plagiarism and professional practice.
AB  - With the ever-increasing availability and accessibility of the Internet, students
      are able to access a multitude of resources in support of their studies. However,
      this has also led to an increase in their ability to cheat through plagiarising
      text and claiming it as their own. Increased pressures of balancing work and
      study have contributed to this rise. Not only confined to the student population,
      some academics are also guilty of engaging in this practice providing a less than
      favourable role model for their students. Of increasing concern is the links of
      this practice to professionalism or indeed in this case unprofessionalism. Both
      pre- and post-registration nursing students who plagiarise risk bringing the
      reputation of the profession into disrepute. There are a number of methods that
      may be used to detect plagiarism but often the penalties are menial and
      inconsistently applied. Overall it is essential that academic institutions foster
      a culture of honesty and integrity amongst its academic community. A culture that
      clearly emphasises that plagiarism in any form is unacceptable.

PMID- 16624456
TI  - Reflections on reflection--a response to Dr. Burnard's editorial.

PMID- 16624457
TI  - Safety and immunogenicity of the modified adult tick-borne encephalitis vaccine
      FSME-IMMUN: results of two large phase 3 clinical studies.
AB  - A prospective, randomised, multicentre, single-blind phase 3 study was performed
      to assess the safety of a vaccination schedule consisting of two vaccinations (21
      35 days apart) with the tick-borne encephalitis (TBE) vaccine FSME-IMMUN "adults"
      (five consecutive lots) in comparison to another licensed TBE vaccine (Encepur),
      with polygeline) (two lots) in healthy volunteers (n=3966) aged 16-65 years. The
      safety of the third vaccination with FSME-IMMUN "adults" (6 months after the
      first vaccination) was investigated in a follow-up study on the same population
      (n=3705) and TBE antibody titres were analysed pre- and post-vaccination in a
      subgroup of volunteers (n=564). Following the first vaccination, the overall
      incidence of fever (> or =38.0 degrees C) was 0.8% in the FSME-IMMUN "adults"
      study group and 5.6% in the comparator study group; fever was mainly mild. The
      fever rate after the second vaccination was 0.6% and 0.5% in the two study
      groups, respectively. Local and systemic reactions after the first vaccination
      occurred with a lower frequency in the FSME-IMMUN "adults" study group than in
      the comparator group. Upon analysing the tolerability of the third vaccination
      with FSME-IMMUN "adults", similar results were determined in both study groups of
      volunteers previously vaccinated with FSME-IMMUN "adults" or with the comparator
      vaccine. The immunogenicity results demonstrated similar seroconversion rates (as
      determined by ELISA or neutralization test) before and after the third
      vaccination in the FSME-IMMUN "adults" group and in the comparator group
      respectively. The results of both studies demonstrate that: (1) FSME-IMMUN
      "adults" is safe and highly immunogenic, (2) all five production lots of FSME
      IMMUN "adults" were consistent with respect to a low rate of adverse events, (3)
      FSME-IMMUN "adults" induces considerably lower adverse reaction rates than the
      comparator vaccine after the first vaccination, and (4) two vaccinations with the
      comparator vaccine can be successfully followed by a third vaccination with FSME
      IMMUN "adults".

PMID- 16624458
TI  - Incidence of influenza in Ontario following the Universal Influenza Immunization
      Campaign.
AB  - The purpose of this study was to determine whether the incidence of influenza in
      Ontario, Canada has decreased following the introduction of the Universal
      Influenza Immunization Campaign (UIIC) in 2000. All laboratory-confirmed
      influenza cases in Ontario, from January 1990 to August 2005 were analyzed using
      multitaper time series analysis. We found that there has not been a decrease in
      the mean monthly influenza rate following the introduction of the UIIC (109.5
      (S.D. 20) versus 160 (S.D. 50.3) p>0.1). Despite increased vaccine distribution
      and financial resources towards promotion, the incidence of influenza in Ontario
      has not decreased following the introduction of the UIIC.

PMID- 16624459
TI  - Timing and presentation of recurrent oral and oropharyngeal squamous cell
      carcinoma and awareness in the outpatient clinic.
AB  - The aim of this study was to assess the timing of outpatient review appointments
      in relation to tumour recurrence. A retrospective review of 278 consecutive
      previously untreated patients with oral and oropharyngeal squamous cell carcinoma
      (SCC) between 1995 and 1999 was performed. Information on the time of recurrence,
      site, presentation, treatment and outcome was collected. There were 54 (19%)
      patients who developed recurrent disease. Recurrence occurred at a median time of
      8 months after the initial operation and most (49/54) within 2 years. Thirty-five
      patients (65%) presented with a new lump (7 local, 22 regional and 5
      locoregional). Our policy is to review patients once a month for the first year
      and every other month for the second year. Patients were seen less frequently
      than expected, and one in five patients attended half or less than half as
      frequently as intended in the first year. Although 20 patients were aware of new
      symptoms from their recurrent disease fewer than half (9) brought their
      appointment forward. This study has emphasised the need for close clinical follow
      up of patients previously treated for oral/oropharyngeal SCC if recurrent tumours
      are to be discovered and treated at the earliest opportunity.

PMID- 16624460
TI  - Human patellar tendon moment arm length: measurement considerations and clinical
      implications for joint loading assessment.
AB  - Detailed understanding of the knee joint loading requires the calculation of
      muscle and joint forces in different conditions. In these applications the
      patellar tendon moment arm length is essential for the accurate estimation of the
      tibiofemoral joint loading. In this article, different methods that have been
      used to determine the patellar tendon moment arm length under in vivo and in
      vitro conditions are reviewed. The limitations and advantages associated with
      each of the methods are evaluated together with their applications in the
      different loading conditions that the musculoskeletal system is subjected to. The
      three main measurement methods that this review considers are the geometric
      method, the tendon excursion method and the direct load method. A comparison of
      relevant quantitative results is presented to asses the impact of the errors of
      each method on the quantification of the patellar tendon moment arm and the
      implications for joint loading assessment in clinical applications.

PMID- 16624461
TI  - Cognitive-behavioural theory and therapy for obsessive-compulsive disorder in
      children and adolescents: current status and future directions.
AB  - Obsessive-compulsive disorder is recognised to be much more common than once
      thought, and increased awareness of prevalence has been associated with an
      increase in clinical and research attention. However, while the cognitive
      behavioural model of OCD has received considerable empirical support from adult
      studies, there has been relatively little investigation of this model in
      childhood populations. Although this literature is beginning to emerge, initial
      evaluations suggest there may be important differences between childhood and
      adult OCD with regard to the cognitive, behavioural, and family factors
      implicated in the etiology and maintenance of the disorder. Despite this,
      cognitive-behavioural interventions have been largely modelled on their adult
      counterparts, and there has been little evaluation of the effectiveness of
      various treatment components. This paper therefore seeks to critically review the
      current status of CBT for children and adolescents with OCD, addressing both
      cognitive behavioural theory and therapy. Current issues in clinical practice
      will be identified, gaps in the knowledge base will be highlighted, and the paper
      will conclude by making specific recommendations regarding the integration of
      research and practice.

PMID- 16624462
TI  - Updated weight of evidence for an association between adverse reproductive and
      developmental effects and exposure to disinfection by-products.
AB  - Disinfection by-products (DBP) are produced when water is treated with chemical
      disinfectants. Some toxicological and epidemiological studies suggest an
      association between DBP exposure and adverse reproductive and developmental
      effects. In a previous critical review, [Graves, C.G., Matanoski, G.M., Tardiff,
      R.G., 2001. Weight of evidence for an association between adverse reproductive
      and developmental effects and exposure to disinfection by-products: a critical
      review. Regul. Toxicol. Pharmacol. 34, (2) 103-124] evaluated the weight of
      evidence for this exposure and these effects. This investigation updates the
      previous evaluation and considers all toxicological and epidemiological evidence
      since the earlier review and reassesses the weight-of-evidence for all of the
      data on the various effects, outcome by outcome. The updated toxicity weight of
      evidence found little indication of previously unreported reproductive or
      developmental toxicity. In particular, the recently published findings of an
      exceptionally well conducted cohort study of broad scope found no impact of
      chlorination by-products on the highly controversial outcome of spontaneous
      abortion, unlike predecessor studies of more limited methodology, leading the
      authors to recommend no further epidemiologic pursuit for this hypothesis since
      the cohort was scrutinized very closely and dispelled any concern of such an
      association. The updated epidemiologic weight of evidence demonstrated that no
      association with DBP exposure exists for over a dozen outcomes including low and
      very low birth weight, preterm delivery, some specific congenital anomalies, and
      neonatal death. The analysis found inconsistent or very weak results for all
      congenital anomalies/birth defects, all central nervous system anomalies, neural
      tube defects, and spontaneous abortion. As in the previous article, the updated
      weight of evidence suggested a positive association with DBP exposure and some
      measure of growth retardation such as intrauterine growth retardation, small for
      gestational age, term low birth weight, and small body length or head
      circumference. Exposure assessment in most epidemiological studies remains
      inadequate to definitively demonstrate any association of small magnitude.

PMID- 16624463
TI  - The development and regulation of occupational exposure limits in Singapore.
AB  - Singapore is an island republic in South East Asia with a workforce of about 2.1
      million including 0.7 million employed in the manufacturing industry. Singapore's
      industry is diversified and the main growth sectors include microelectronics,
      chemical, petrochemical, pharmaceutical, and biomedical sectors. Exposure to
      chemical hazards is one of the main occupational health problems in the
      manufacturing sectors. The main roles of government in the protection of workers
      against safety and health hazards are to set standards and provide a proper
      infrastructure for industry to self-regulate. The occupation safety and health
      laws must provide adequate protection of workforce but must not disadvantage
      local industry in this globally competitive economy. To ensure a level playing
      field, Singapore's occupational exposure standards are benchmarked against those
      established in the developed countries. These standards are reviewed regularly to
      ensure they are realistic and relevant in tandem with worldwide trends. Industry
      and stakeholders are consulted before any new standards are introduced. In
      enforcing the laws relating to exposure standards, legal and administrative
      procedures are followed to ensure fairness and to prevent abuse.

PMID- 16624464
TI  - The development and regulation of occupational exposure limits in China.
AB  - Of the 700 million workers in China, approximately 200 million workers are
      potentially exposed to industrial hazards. Although the promulgation and
      implementation of occupational exposure limits (OELs) in China began in the mid
      1950, a systematic approach was not formalized until the formation of the
      Subcommittee of Occupational Health Standards Setting (SOHSS) in 1981. More
      recently, the 2002 Occupational Disease Prevention and Control Act of the
      People's Republic of China created the legislative framework for the development
      and enforcement of OELs. The SOHSS, whose members are primarily health
      professionals, is the organization responsible for the development of recommended
      standards, under the auspices of the Ministry of Health. The philosophy of OEL
      development of the SOHSS consists of a two-step approach: (1) an initial health
      based recommended standard is established based on scientific data, and (2) a
      final law-based standard takes into consideration both socioeconomic and
      technological feasibility. Governmental agencies such as the Centers for Diseases
      Control and Prevention and the Institutes of Public Health Supervision at the
      state, provincial or municipal levels are charged with the responsibilities of
      the enforcement of OELs. The process and challenges in the enforcement of OELs
      are discussed. A comparison is made between selected Chinese OELs and those in
      other countries. The OELs for benzene and industrial dusts (including silica) are
      discussed in some detail.

PMID- 16624465
TI  - When one's main effect is another's error: material vs. psychosocial explanations
      of health disparities. A commentary on Macleod et al., "is subjective social
      status a more important determinant of health than objective social status?
      Evidence from a prospective observational study of Scottish men" (61(9), 2005,
      1916-1929).
AB  - Two pathways by which socioeconomic factors result in health disparities are the
      material and the psychosocial. Recently, Macleod and colleagues reported on data
      showing that a subjective measure of workplace status was not as strongly related
      to mortality as were objective indicators and that another psychosocial measure,
      perceived stress, did not mediate the impact of these indicators [Macleod et al.,
      2005. Is subjective social status a more important determinant of health than
      objective social status? Evidence from a prospective observational study of
      Scottish men. Social Science & Medicine, 61(9), 1916-1929]. They suggest that the
      failure of these variables is indicative of the relative insignificance of
      psychosocial influences on health. This commentary argues for a different
      approach to examining these pathways. Efforts to demonstrate the failure of
      variables to predict health have the usual difficulties of trying to prove the
      null hypothesis. In this instance, problems in the conceptualization and
      measurement of psychosocial variables may account for the null results.
      Psychosocial and material factors are not mutually exclusive but, rather, are
      complementary. Unexplained variation in health when material factors are
      accounted for may be explained in part by psychosocial factors and vice versa.
      Collaboration between researchers who understand each of these domains will yield
      the greatest benefit in terms of understanding the processes leading to health
      disparities and providing multiple approaches for eliminating them.

PMID- 16624466
TI  - Evolutionary psychiatry: integrating evolutionary theory and modern psychiatry.

PMID- 16624468
TI  - Ziprasidone-associated pedal edema in the treatment of schizophrenia.
AB  - It has been reported that second generation of antipsychotic drugs may induce
      pedal edema. The purpose of this case report is to demonstrate that the recently
      marketed antipsychotic drug, ziprasidone induced pedal edema with an increased
      plasma immunoglobulin E (IgE) level. A 51-year-old female schizophrenic patient
      who developed severe pedal edema was treated with ziprasidone for 6 weeks.
      Admission routine data that included biochemical, blood and urine analysis were
      normal except for the plasma IgE level, which was significantly elevated.
      Although the pedal edema subsided after discontinuation of ziprasidone and
      administration of diuretics, the plasma IgE level remained high. This is the
      first case report attempting to demonstrate the existence of ziprasidone-induced
      pedal edema in the treatment of schizophrenia. In this case, the pedal edema was
      associated with an IgE-related allergic reaction.

PMID- 16624467
TI  - Mirtazapine for patients with alcohol dependence and comorbid depressive
      disorders: a multicentre, open label study.
AB  - Major depressive disorder and alcohol dependence are common and serious mental
      illnesses. There is a great interest in discovering useful treatments for both
      mood symptoms and alcohol abuse in those patients with depressive disorders and
      comorbid alcohol dependence. The primary purpose of this study was to evaluate
      the effectiveness and tolerability of mirtazapine for the treatment of patients
      with alcohol dependence comorbid with a depressive disorder in an open label,
      naturalistic multicentre treatment setting. The 17-item Hamilton Depression
      Rating Scale (HDRS), the Hamilton Anxiety Rating Scale (HARS) and the Clinical
      Global Impression-Severity (CGI-S) scale were measured at baseline and at weeks 4
      and 8 for the assessment of treatment effectiveness. Alcohol craving was measured
      using the Obsessive Compulsive Drinking Scale (OCDS) and the Visual Analog Scale
      for Craving (VAS). This study showed a statistically significant reduction of the
      scores on the HDRS (13.9+/-7.3, p<0.0001), HARS (10.8+/-7.2, p<0.0001) and the
      CGI-S (1.7+/-1.0, p<0.0001) from baseline to the endpoint (week 8). The OCDS and
      VAS scores were also decreased significantly by 42.3% and 53.2% (9.0+/-10.0,
      p<0.0001; 2.5+/-2.4, p<0.0001, respectively). The number of patients with a 50%
      reduction or more in the HDRS and HARS scores was 103 (72.0%) and 106 (74.1%) at
      the endpoint, respectively. Adverse events related to mirtazapine were observed
      in 10% or more of the patients in this study. In conclusion, the results from
      this naturalistic study suggest that the use of mirtazapine for the patients with
      alcohol dependence comorbid with depressive disorder is accompanied by clinical
      improvement in their mood and alcohol craving.

PMID- 16624469
TI  - Bovine brain phosphatidylserine attenuates scopolamine induced amnesia in mice.
AB  - This study verifies the effects of bovine brain phosphatidylserine (PS) on
      passive avoidance (PA) and contextual fear conditioning (CFC) tests in
      scopolamine-treated mice. Mice received daily i.p. 50 mg/kg PS or 0.2 M Tris pH
      7.4 (TRIS) for 5 days. On day 6, mice received saline (TRIS-SAL and PS-SAL) or 1
      mg/kg SCO (TRIS-SCO and PS-SCO) i.p. After 20 min, the animals were submitted to
      PA (experiment 1) or CFC (experiment 2) training sessions, and tests were
      performed 24 h later. Latency in entering the dark chamber of the PA apparatus
      presented by TRIS-SCO (but not PS-SCO) group in the test was significantly higher
      than those presented by controls. Except for TRIS-SCO, all the groups presented
      higher latencies in the test compared to the training session. In experiment 2,
      the TRIS-SCO (but not PS-SCO) group presented significantly lower freezing
      duration than that presented by the TRIS-SAL group in the test. Animals treated
      with PS alone presented higher freezing duration than that presented by the TRIS
      SAL group. The results demonstrate that PS attenuates SCO-induced amnesia in both
      PA and CFC tests. In addition, PS per se improves retention in the CFC test.

PMID- 16624470
TI  - Developmental toxicity of combined ethylbenzene and methylethylketone
      administered by inhalation to rats.
AB  - Pregnant Sprague-Dawley rats were exposed to ethylbenzene (EB; 0, 250, or 1000
      ppm) and methylethylketone (MEK; 0, 1000, or 3000 ppm), alone and in combination,
      by inhalation, for 6h/day, during days 6-20 of gestation. Maternal toxicity,
      evidenced by decreased in body weight gain and food consumption, tended to be
      greater after simultaneous exposures to the high concentrations of 1000 ppm EB
      and 3000 ppm MEK, when compared to the treatments with individual compounds. No
      significant increase in embryo/fetal lethality or incidence of malformations and
      variations was observed in any of the treatment groups. Fetal body weight was
      significantly reduced after individual treatment with 1000 ppm EB or 3000 ppm
      MEK, and in the combined groups. There was no evidence of interaction between EB
      and MEK in causing developmental toxicity.

PMID- 16624471
TI  - Dosage effects of curcumin on cell death types in a human osteoblast cell line.
AB  - Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and
      anti-inflammatory properties, as well as their ability to either induce or
      prevent cell apoptosis. However, the precise molecular mechanisms of these
      effects are unknown. Here, we demonstrate that curcumin can induce apoptotic
      changes, including JNK activation, caspase-3 activation, and cleavage of PARP and
      PAK2, at treatment concentrations lower than 25 microM in human osteoblast cells.
      In contrast, treatment with 50-200 microM of curcumin does not induce apoptosis,
      but rather triggers necrotic cell death in human osteoblasts. Using the cell
      permeable dye 2',7'-dichlorofluorescin diacetate (DCF-DA) as an indicator of
      reactive oxygen species (ROS) generation, we found that while treatment with 12.5
      25 microM curcumin directly increased intracellular oxidative stress, 50-200
      microM curcumin had far less effect. Pretreatment of cells with N-acetyl cysteine
      or alpha-tocopherol, two well known ROS scavengers, attenuated the intracellular
      ROS levels increases and converted the apoptosis to necrosis induced by 12.5-25
      microM curcumin. Moreover, we observed a dose-dependent decrease in intracellular
      ATP levels after treatment of osteoblast cells with curcumin and pretreatment of
      cells with antimycin or 2-deoxyglucose to cause ATP depletion significantly
      converted 12.5-25 microM curcumin-induced apoptosis to necrosis, indicating that
      ATP (a known mediator of apoptotic versus necrotic death) is most likely involved
      in the switching mechanism. Overall, our results signify that curcumin dosage
      treatment determines the possible effect on ROS generation, intracellular ATP
      levels, and cell apoptosis or necrosis in osteoblast cells.

PMID- 16624472
TI  - Pro-oxidant and cytotoxic activities of atractylenolide I in human
      promyeloleukemic HL-60 cells.
AB  - The dried rhizome of Bai Zhu (Atractylodes ovata) is widely used as a Chinese
      herbal medicine. Two sesquiterpenolides of similar structures (atractylenolide I,
      AT-I; atractylenolide III, AT-III) were isolated from dried rhizome of
      Atractylodes ovata. Incubation of AT-I with recombinant human Cu,Zn-superoxide
      dismutase (rhCu,Zn-SOD) resulted in rhCu,Zn-SOD fragmentations and Zn releases.
      However, these were not observed in the AT-III reaction. The AT-1 showed dose
      dependent cytotoxic activities (7.5, 15, and 30 microg/ml) on the human
      promyeloleukemic HL-60 cells while AT-III did not, and the IC50 of the former
      being 10.6 microg/ml (corresponding to 46 microM) on 12 h-treated cells. The
      results of DNA ladder and DNA contents in sub-G1 type revealed that AT-I induced
      apoptosis in human promyeloleukemic HL-60 cells. The cytotoxic and
      pharmacological mechanisms of AT-I against human promyeloleukemic HL-60 cells was
      investigated. The AT-I appeared to exhibit both pro-oxidant and antioxidant
      properties after an ESR spectrometer was used to detect hydroxyl radical
      productions in vitro and flow cytometry to detect intracellular ROS productions
      in AT-I treated cells. The AT-1 also showed dose-dependent Cu,Zn-SOD inhibitory
      activity in HL-60 cells treated for 12 h, confirmed by activity and immune
      stainings. However, catalase, Mn-SOD, and glutathione peroxidase did not
      apparently change activities under the same treatments. The addition of
      commercial rhCu,Zn-SOD (25-100 U/mL) to the AT-I-treated HL-60 cells (15
      microg/ml) resulted in significant differences (p<0.01) and could reduce the AT-I
      cytotoxicity from 78% to 28% on HL-60 cells. It was proposed that the AT-I might
      work via Cu,Zn-SOD inhibition in HL-60 cells to induce apoptosis and bring about
      cytotoxicity.

PMID- 16624473
TI  - Murine strain differences in 8-hydroxy-deoxyguanosine formation in hepatic DNA
      induced by oxidized lard and dietary oils.
AB  - Difference of 8-hydroxy-deoxyguanosine (8-OH-dG) formation in liver DNA in
      C3H/HeN and in C57BL/6 mice--fed oxidized lard and dietary oils (soybean and
      sardine)--was investigated. The blank levels of 8-OH-dG were higher in C3H/HeN
      mice (highly sensitive to liver tumorigenesis) than in C57BL/6 mice (resistant
      strain). The level of 8-OH-dG increased much more in C3H/HeN mice than in the
      C57BL/6 mice fed by oxidized lard and dietary oil treatment. Feeding oxidized
      lard and dietary oils increased 8-oxo-guanine DNA glycosylase I (OGG1) and mRNA 8
      oxo-dGTPase in C57BL/6 mice. On the other hand, no appreciable change of mRNA in
      the C3H/HeN mice was observed. The formation differences of 8-OH-dG from the two
      murine strains fed with oxidized lard and dietary oils may be associated with the
      different mRNA levels in the DNA repair enzymes because the mRNA levels in the
      DNA repair enzymes were much lower in C3H/HeN mice than in C57BL/6 mice.

PMID- 16624474
TI  - Effect of different Thai traditional processing of various hot chili peppers on
      urethane-induced somatic mutation and recombination in Drosophila melanogaster:
      assessment of the role of glutathione transferase activity.
AB  - Four different Thai traditional chili peppers, namely bird pepper (Capsicum
      frutescens), red chili spur peppers (Capsicum annuum), green bell peppers and
      sweet pepper (C. annuum) were investigated for their antimutagenic properties.
      Each chili was prepared in three formulations commonly used for chili food
      processing; raw paste (chili ground in water), pickled in vinegar or stir-fried
      in palm oil. Each sample was tested for its antimutagenic effect against urethane
      by using the somatic mutation and recombination of wing hair of Drosophila
      melanogaster as an indicator. Three-day-old larvae, trans-heterozygous for two
      genetic markers, multiple wing hairs mwh and orrigon (ORR;flr3), were exposed to
      urethane alone or in combination with each chili formulation. The various
      processing methods for chilies differentially extracted the antimutagenic chili
      components. The specific chili as well as the method of processing influenced the
      observed antimutagenic properties against urethane. This suggested each chili
      contains a unique complex mixture of many antimutagens. Co-treatment and pre
      treatment experiments showed that both direct and indirect protective mechanisms
      are involved in an 'activation' process to give antimutagenesis effects. An
      association between antigenotoxicity and glutathione transferase activity could
      not be established.

PMID- 16624475
TI  - Comparing mono- and divalent DNA groove binding cyanine dyes -- binding
      geometries, dissociation rates, and fluorescence properties.
AB  - The unsymmetrical cyanine dyes BOXTO-PRO and BOXTO-MEE were derived from the DNA
      groove binder BOXTO, by adding a positively charged or a non-ionic hydrophilic
      tail to BOXTO, respectively. The main objective was to obtain more efficient DNA
      probes, for instance in electrophoresis and microscopy, by slowing down the
      dissociation of BOXTO from DNA. The interactions with mixed sequence DNA was
      studied with fluorescence and absorbance spectroscopy, stopped-flow dissociation
      and gel electrophoresis. Both the derivatives are groove bound as BOXTO, and have
      similar fluorescence properties when bound to mixed sequence DNA in free
      solution. BOXTO-PRO exhibits a slower dissociation than BOXTO from DNA, whereas
      the dissociation rate for BOXTO-MEE is faster and, unexpectedly independent of
      the ionic strength. During gel electrophoresis both BOXTO-PRO and BOXTO-MEE
      exhibit a faster dissociation rate than BOXTO. Still, BOXTO-PRO seems to be a
      good alternative as DNA probe, especially for applications in free solution where
      the dissociation is slower than for the corresponding intercalator TOPRO-1.

PMID- 16624476
TI  - Electron-transfer mechanism of the triplet state quenching of aluminium
      tetrasulfonated phthalocyanine by cytochrome c.
AB  - The mechanism of electron-transfer from aluminium tetrasulfonated phthalocyanine
      triplet state to cytochrome c was investigated in this work. This reaction
      successfully quenches the dye triplet state due to the formation of complexes
      between the solute and the protein at the active site. The electron-transfer rate
      constant is around 3x10(7) s(-1), and is in accordance with previous results for
      the singlet excited state quenching [C.A.T. Laia, S.M.B. Costa, D. Phillips, A.
      Beeby. Electron-transfer kinetics in sulfonated aluminum
      phthalocyanines/cytochrome c complexes, J. Phys. Chem. B 108 (2004) 7506-7514.]
      in the framework of the Marcus theory, with a reorganization energy equal to 0.94
      eV. The complex formation is diffusion controlled, but heterogeneities of the
      protein surface charge distribution lead to quenching rate constants smaller than
      predicted on a hard-spheres model with electrostatic interactions. Also the
      binding equilibrium constant is strongly affected by this phenomenon. Ionic
      strength plays an important role on the complex formation, but its effect on the
      unimolecular electron-transfer rate constant is negligible within experimental
      error.

PMID- 16624477
TI  - Degradation of a commercial textile biocide with advanced oxidation processes and
      ozone.
AB  - The occurrence of significant amounts of biocidal finishing agents in the
      environment as a consequence of intensive textile finishing activities has become
      a subject of major public health concern and scientific interest only recently.
      In the present study, the treatment efficiency of selected, well-known advanced
      oxidation processes (Fenton, Photo-Fenton, TiO(2)/UV-A, TiO(2)/UV-A/H(2)O(2)) and
      ozone was compared for the degradation and detoxification of a commercial textile
      biocide formulation containing a 2,4,4'-trichloro-2'-hydroxydiphenyl ether as the
      active ingredient. The aqueous biocide solution was prepared to mimic typical
      effluent originating from the antimicrobial finishing operation (BOD(5,o) < or =5
      mg/L; COD(o)=200 mg/L; DOC(o) (dissolved organic carbon)=58 mg/L; AOX(o)
      (adsorbable organic halogens)=48 mg/L; LC(50,o) (lethal concentration causing 50%
      death or immobilization in Daphnia magna)=8% v/v). Ozonation experiments were
      conducted at different ozone doses (500-900 mg/h) and initial pH (7-12) to assess
      the effect of ozonation on degradation (COD, DOC removal), dearomatization
      (UV(280) and UV(254) abatement), dechlorination (AOX removal) and detoxification
      (changes in LC(50)). For the Fenton experiments, the effect of varying ferrous
      iron catalyst concentrations and UV-A light irradiation (the Photo-Fenton
      process) was examined. In the heterogenous photocatalytic experiments, Degussa
      P25-type TiO(2) was used as the catalyst and the effect of reaction pH (3, 7 and
      12) and H(2)O(2) addition on the photocatalytic treatment efficiency was
      examined. Although in the photochemical (i.e. Photo-Fenton, TiO(2)/UV-A and
      TiO(2)/UV-A/H(2)O(2)) experiments appreciably higher COD and DOC removal
      efficiencies were obtained, ozonation appeared to be equally effective to achieve
      dearomatization (UV(280) abatement) at all studied reaction pH. During ozonation
      of the textile biocide effluent, AOX abatement proceeded significantly faster
      than dearomatization and was complete after 20 min ozonation (267 mg O(3)). On
      the other hand, for complete detoxification, ozonation had to be continued for at
      least 30 min (corresponding to 400mg O(3)). Effective AOX and acute toxicity
      removal was also obtained after heterogeneous photocatalytic treatment (TiO(2)/UV
      A and TiO(2)/UV-A/H(2)O(2)). The Fenton-based treatment experiments and
      particularly the dark Fenton reaction resulted in relatively poor degradation,
      dearomatization, AOX and acute toxicity removals.

PMID- 16624478
TI  - Toward quantifying the effectiveness of water trading under uncertainty.
AB  - This paper presents a methodology for quantifying the effectiveness of water
      trading under uncertainty, by developing an optimization model based on the
      interval-parameter two-stage stochastic program (TSP) technique. In the study,
      the effectiveness of a water-trading program is measured by the water volume that
      can be released through trading from a statistical point of view. The methodology
      can also deal with recourse water allocation problems generated by randomness in
      water availability and, at the same time, tackle uncertainties expressed as
      intervals in the trading system. The developed methodology was tested with a
      hypothetical water-trading program in an agricultural system in the Swift Current
      Creek watershed, Canada. Study results indicate that the methodology can
      effectively measure the effectiveness of a trading program through estimating the
      water volume being released through trading in a long-term view. A sensitivity
      analysis was also conducted to analyze the effects of different trading costs on
      the trading program. It shows that the trading efforts would become ineffective
      when the trading costs are too high. The case study also demonstrates that the
      trading program is more effective in a dry season when total water availability
      is in shortage.

PMID- 16624479
TI  - The positive surgical margin after radical prostatectomy--why do we still not
      really know what it means?

PMID- 16624480
TI  - Urethra reconstruction following resection of penile leiomyosarcoma.
AB  - Leiomyosarcoma is a rare tumor, particularly in genital area. We present a case
      of penile lyomyosarcoma. Surgical treatment involved subcutaneous penectomy,
      preserving a sensate skin envelope, bilateral groin dissection and perineal
      urethrostomy. Reconstruction of the urethra and soft tissue was carried out using
      a free radial forearm flap. We believe that subcutaneous penectomy should be
      considered as a treatment option in selected cases of penile tumor as this
      facilitates urethral reconstruction.

PMID- 16624481
TI  - Primary care seeking--do we know who needs and seeks?

PMID- 16624482
TI  - Molecular and immunohistochemical analysis of the prognostic value of cell-cycle
      regulators in urothelial neoplasms of the bladder.
AB  - OBJECTIVE: To evaluate the prognostic and predictive value of molecular and
      immunohistochemical markers related to cell-cycle control in terms of recurrence,
      progression, and survival in urothelial neoplasms of the bladder (UNB). PATIENTS
      AND METHODS: Clinical and pathological findings of 84 patients with UNB were
      assessed. Homozygous deletion (HD) and promoter methylation of p14ARF, p15INK4B,
      p16INK4A, loss of heterozygosity of the locus 9p21, p53 mutations, and
      immunohistochemical expression of p53, p16, p14, p21, p27, pRb, Ki67, MDM2, and
      cyclin D1 proteins were evaluated in relation to overall survival (OS),
      recurrence-free survival (RFS), and progression-free survival (PFS). RESULTS: In
      the univariate analysis, RFS was shorter in cases with p14ARF (p=0.006), p15INK4B
      (p=0.003), p16INK4A (p=0.03) HD, low p14 immunoreactivity index (IRI) (p=0.01)
      and high Ki67 IRI (p=0.04); HD of the 9p21 locus genes and p14 IRI remained as
      independent prognostic factors for early UNB recurrence (p=0.006) whereas tumour
      stage (p=0.00001) and cyclin D1 IRI (p=0.049) were related to worse PFS in the
      multivariate analysis. In the univariate analysis, IRI for Ki67 (p=0.002), cyclin
      D1 (p=0.06), p53 (p=0.00008), p16 (p=0.02), p27 (p=0.0005) MDM2 (p=0.01) and p53
      mutations (p=0.03) were related to poor OS, and only the Ki67 IRI retained their
      independent value in the multivariate analysis. CONCLUSION: 9p21 HD and p14 IRI
      constitute independent predictive factors for UNB recurrence and cyclin D1 IRI
      and tumour stage for progression. In addition, Ki67 IRI and tumour stage are
      independent prognostic factors for overall survival in UNB.

PMID- 16624483
TI  - Multiphasic disseminated encephalomyelitis, systemic lupus erythematosus and
      antiphospholipid syndrome.
AB  - We report a case of multiphasic disseminated encephalomyelitis (MDEM) associated
      with systemic lupus erythematosus (SLE) and antiphospholipid syndrome. The
      initial presentation was suggestive of multiple sclerosis. Further clinical
      attacks, MRI imaging, and CSF findings led to a diagnosis of disseminated
      encephalomyelitis (DEM). Multiple episodes of neurological dysfunction, which
      differed in clinical presentation, further categorized the diagnosis as
      multiphasic DEM. The co-occurrence SLE and antiphospholipid syndrome is unusual
      and provided an additional diagnostic challenge.

PMID- 16624484
TI  - Trichostatin A down-regulate DNA methyltransferase 1 in Jurkat T cells.
AB  - Histone deacetylase inhibitor Trichostatin A (TSA), alone, is able to activate
      the transcription of DNA methylation-mediated silenced genes in human cancer
      cells. Increase in expression and half-life of the DNA methyltransferase DNMT1
      has been found in carcinomas of the colon, lung, liver, prostate, and breast
      cancer. This overexpression of DNMT1 is responsible for hypermethylation of
      regulatory sequences of many genes involved in tumorigenesis. Using quantitative
      real-time PCR and Western blot analysis, we found that TSA down-regulate DNMT1
      mRNA and protein expression in Jurkat T leukemia cells clone E6-1. We also
      observed that TSA decreased DNMT1 mRNA stability and reduced this transcript half
      life from approximately 7 to 2h. We also found that protein biosynthesis is
      needed for posttranscriptional regulation of DNMT1 mRNA, which suggests the
      involvement of an RNase and/or mRNA stabilization protein entity in DNMT1
      transcript stabilization. Our findings suggest that TSA not only alters histone
      acetylation, but also may affect DNA methylation.

PMID- 16624485
TI  - Methylation status of the Ep-CAM promoter region in human breast cancer cell
      lines and breast cancer tissue.
AB  - We examined the methylation status of the Ep-CAM promoter region of human breast
      cancer cell lines and breast cancer tissue using MethyLight technology and
      bisulfite sequencing. We found the promoter of Ep-CAM-negative breast cancer cell
      lines Hs 578T to be methylated to a higher degree as compared to positive cell
      lines MCF-7. Demethylation of cell lines was performed using 5-aza-2'
      deoxycytidine. Ep-CAM RNA and protein expression could be partially restored by
      treating cells with 5-Aza-2'-deoxycytidine. In most primary breast cancer tissue,
      methylation of the Ep-CAM gene could be detected at a low level and no
      correlation was found with Ep-CAM protein expression in tumour tissue. Taken
      together, these data suggest that methylation of the Ep-CAM promoter is not a
      crucial mechanism for regulation of Ep-CAM expression in breast cancer. Thus,
      most important regulatory mechanisms have to be supposed in vivo.

PMID- 16624486
TI  - The effect of smoking and drinking in oral and pharyngeal cancers: a case-control
      study in Uruguay.
AB  - In the time period 1988-2000, a case-control study on oral and pharyngeal cancers
      was conducted among men in Montevideo, Uruguay. The study included 776 cases and
      1501 controls. The cases were distributed by site in oral cancers (335 patients)
      and pharyngeal cancers (441 patients). Odds ratios for smoking were higher among
      participants with pharyngeal cancers compared with those with oral carcinomas,
      but there was no significant heterogeneity. On the contrary, alcohol drinking
      displayed statistically higher risks among those with pharyngeal carcinomas
      compared with patients with oral cancer (P-value for heterogeneity=0.01). The
      effect of alcohol was particularly strong for cancers of the hypopharynx. Our
      results raise the possibility that oral and pharyngeal carcinomas are in fact
      different entities. Further studies are needed in order to clarify this important
      point.

PMID- 16624487
TI  - Metabolism of oxidized linoleic acid by glutathione transferases: peroxidase
      activity toward 13-hydroperoxyoctadecadienoic acid.
AB  - The oxidation of linoleic acid produces several products with biological activity
      including the hydroperoxy fatty acid 13-hydroperoxyoctadecadienoic acid (13
      HPODE), the hydroxy fatty acid 13-hydroxyoctadecadienoic acid (13-HODE), and the
      2,4-dienone 13-oxooctadecadienoic acid (13-OXO). In the present work, the
      peroxidase activity of glutathione transferases (GST) A1-1, M1-1, M2-2, and P1
      1(Val 105) toward 13-HPODE has been examined. The alpha class enzyme is the most
      efficient peroxidase while the two enzymes from the mu class exhibit weak
      peroxidase activity toward 13-HPODE. It was also determined that the conjugated
      diene 13-HODE is not a substrate for GST from the alpha and mu classes but that
      13-HODE does inhibit the GST-catalyzed conjugation of CDNB by enzymes from the
      alpha, mu, and pi classes. Finally, both 13-HODE and 13-OXO were shown to be
      inducers of GST activity in HT-29 and HCT-116 colon tumor cells. These data help
      to clarify the role of GST in the metabolic disposition of linoleic acid
      oxidation products.

PMID- 16624488
TI  - Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway
      inflammation in a mouse model of allergic asthma.
AB  - Chronic airway inflammation is a key feature of bronchial asthma. Leukotrienes
      are potent inflammatory mediators that play a role in the pathophysiology of
      asthma, and their levels are elevated in the airways in response to allergen
      challenge. We examined the anti-inflammatory effect of thymoquinone (TQ), the
      active principle in the volatile oil of Nigella sativa seeds, on leukotriene (LT)
      biosynthesis in a mouse model of allergic asthma. Mice sensitized and challenged
      with ovalbumin (OVA) antigen had an increased amounts of leukotriene B4 and C4,
      Th2 cytokines, and eosinophils in bronchoalveolar lavage (BAL) fluid. In
      addition, there was also a marked increase in lung tissue eosinophilia and goblet
      cell numbers. Administration of TQ before OVA challenge inhibited 5-lipoxygenase,
      the main enzyme in leukotriene biosynthesis, expression by lung cells and
      significantly reduced the levels of LTB4 and LTC4. This was accompanied by a
      marked decrease in Th2 cytokines and BAL fluid and lung tissue eosinophilia, all
      of which are characteristics of airway inflammation. These results demonstrate
      the anti-inflammatory effect of TQ in experimental asthma.

PMID- 16624489
TI  - Interaction of iron-sulfur flavoprotein with oxygen and hydrogen peroxide.
AB  - The dimeric iron-sulfur flavoprotein (Isf) from Methanosarcina thermophila
      contains one 4Fe-4S center and one FMN per monomer, and is the prototype of a
      family widely distributed among strictly anaerobic prokaryotes. Although Isf is
      able to oxidize ferredoxin, the physiological electron acceptor is unknown; thus,
      the ability of Isf to reduce O2 and H2O2 was investigated. The product of O2 or
      H2O2 reduction by Isf was determined to be water. The kinetic parameters of the
      oxidative half-reactions with O2 and H2O2 as electron acceptors were consistent
      with a role for Isf in combating oxidative stress. Isf depleted of the 4Fe-4S
      cluster was unable to oxidize ferredoxin and reduce the FMN cofactor, supporting
      a role for the cluster in transfer of electrons from ferredoxin to the cofactor.
      The implications of these properties on the possible function and mechanism of
      Isf are discussed.

PMID- 16624491
TI  - High-quality evidence in oncology from 3 November to 24 November, 2005: a
      summary.

PMID- 16624490
TI  - Opioid switching: a systematic and critical review.
AB  - Cancer patients with pain may not respond to increasing doses of opioids because
      they develop adverse effects before achieving an acceptable analgesia, or the
      analgesic response is poor, despite a rapid dose escalation. Opioid switching may
      significantly improve the balance between analgesia and adverse effects. We
      conducted a systematic review of existing literature on opioid switching.
      According to available data, opioid switching results in clinical improvement in
      more than 50% of patients with chronic pain with poor response to one opioid.
      However, data are based on open studies or small case series. Reasons for
      switching may influence the dose of the alternative drug. Opioid conversion
      should not be a mere mathematical calculation, but just a part of a more
      comprehensive evaluation of pain, adverse effect intensity, comorbidities, and
      concomitant drugs. The process of reaching an optimal dose should be highly
      individualized, particularly when patients are switched from high doses of
      opioids, given the wide conversion ratios reported in literature.

PMID- 16624492
TI  - Prenatal stress alters Fos protein expression in hippocampus and locus coeruleus
      stress-related brain structures.
AB  - Prenatal stress (PS) durably influences responses of rats from birth throughout
      life by inducing deficits of the hypothalamo-pituitary-adrenal (HPA) axis
      feedback. The neuronal mechanisms sustaining such alterations are still unknown.
      The purpose of the present study was to determine whether in PS and control rats,
      the exposure to a mild stressor differentially induces Fos protein in hippocampus
      and locus coeruleus, brain areas involved in the feedback control of the HPA
      axis. Moreover, Fos protein expression was also evaluated in the hypothalamic
      paraventricular nucleus (PVN) that reflect the magnitude of the hormonal response
      to stress. Basal plasma corticosterone levels were not different between the
      groups, while, PS rats exhibited higher number of Fos-immunoreactive neurons than
      controls, in the hippocampus and locus coeruleus in basal condition. A higher
      basal expression of a marker of GABAergic synapses, the vGAT, was also observed
      in the hypothalamus of PS rats. Fifteen minutes after the end of the exposure to
      the open arm of the elevated plus-maze (mild stress) a similar increased plasma
      corticosterone levels was observed in both groups in parallel with an increased
      number of Fos-immunoreactive neurons in the PVN. Return to basal plasma
      corticosterone values was delayed only in the PS rats. On the contrary, after
      stress, no changes in Fos-immunoreactivity were observed in the hippocampus and
      locus coeruleus of PS rats compared to basal condition. After stress, only PS
      rats presented an elevation of the number of activated catecholaminergic neurons
      in the locus coeruleus. In conclusion, these results suggest for the first time
      that PS alters the neuronal activation of hippocampus and locus coeruleus
      implicated in the feedback mechanism of the HPA axis. These data give anatomical
      substrates to sustain the HPA axis hyperactivity classically described in PS rats
      after stress exposure.

PMID- 16624493
TI  - Salivary alpha-amylase response to competition: relation to gender, previous
      experience, and attitudes.
AB  - This study examined individual differences in salivary alpha-amylase response to
      competition in relation to gender, previous experience, behavior, attitudes, and
      performance. Participants were 42 (21 women) members of a collegiate crew team.
      Saliva samples were collected before, 20- and 40-min post-ergometer competition
      and at the same times on a non-competition day for comparison. Samples were
      assayed for salivary biomarkers of sympathetic nervous system (alpha-amylase) and
      hypothalamic-pituitary-adrenal axis (cortisol) activity. Behavioral assessments
      included self-reports of dominance, competitiveness, bonding with teammates,
      competition-related strategic thinking, and performance. On average, salivary
      alpha-amylase increased 156% in response to the ergometer competition. By
      comparison, cortisol increased 87% across the same time period. Salivary alpha
      amylase was higher across the competition for varsity than for novice athletes,
      and was positively associated with performance and interest in team-bonding.
      Regression analyses revealed that alpha-amylase reactivity explained individual
      differences in dominance and team bonding above and beyond that associated with
      cortisol reactivity, and that joint inactivation in alpha-amylase and cortisol
      reactivity to competition (low-low) was associated with high perceived dominance.
      The findings are among the first to integrate salivary alpha-amylase into the
      study of competition and reveal that intra-individual change in alpha-amylase may
      be influenced by a confluence of factors that include contextual, behavioral, and
      psychological factors and processes.

PMID- 16624494
TI  - Hypoestrogenism does not mediate social suppression of cortisol in subordinate
      female marmosets.
AB  - Behaviorally subordinate female marmosets undergo social suppression of ovulation
      and hypoestrogenism, as well as chronic reductions in circulating basal cortisol
      concentrations. Because estrogen elevates hypothalamic-pituitary-adrenal axis
      activity and circulating glucocorticoid levels in other species, we tested the
      hypothesis that socially induced hypoestrogenism contributes to cortisol
      reductions in subordinate female marmosets. We characterized morning basal plasma
      cortisol levels, as well as cortisol responses to exogenous adrenocorticotropic
      hormone (ACTH; 0, 1, or 10 microg/kg), in seven anovulatory subordinate females
      and six ovariectomized, non-subordinate females under two conditions: during long
      term treatment with estradiol (E2) and control. Circulating E2 and cortisol
      levels were compared to those of six dominant females undergoing ovulatory
      cycles. Basal cortisol concentrations in the control condition were significantly
      lower in subordinates than in both dominant and ovariectomized females. E2
      treatment elevated circulating E2 levels of subordinate and ovariectomized
      females into the range seen in dominant females but did not increase either mean
      basal or ACTH-stimulated cortisol levels. To the contrary, E2 treatment caused a
      decline in basal cortisol levels over time, especially in ovariectomized animals.
      These results indicate that treatment with exogenous estrogen does not elevate
      circulating cortisol levels in previously hypoestrogenemic female marmosets and,
      correspondingly that socially induced hypoestrogenism does not diminish cortisol
      levels in subordinate females.

PMID- 16624495
TI  - Removal of senescent cells from organisms: A way to retard aging or just
      nonsense?

PMID- 16624496
TI  - A nutritional supplement formula for influenza A (H5N1) infection in humans.
AB  - By early February 2006, the World Health Organization had reported 165 human
      cases of H5N1 influenza since December 2003, with 88 fatalities. However, the
      avian H5N1 influenza virus apparently is not yet efficiently transmitted between
      humans. Though a near-term possibility of a global H5N1 influenza pandemic
      remains, currently there is no vaccine or anti-viral drug that is proven to be
      safe and effective in preventing or treating H5N1 influenza in humans. There is
      thus a compelling public interest in developing alternative prophylaxis and
      treatment strategies for H5N1 influenza, which would need to address the complex
      pathogenesis of H5N1 influenza that is responsible for its apparently unusually
      high virulence. The authors present here a significant body of medical and
      scientific evidence to support the prophylactic use of a carefully designed
      nutritional supplement formulation that may antagonize the major pathogenic
      processes of H5N1 influenza in humans. Through several independently-mediated
      mechanisms, the formulations may: (a) degrade H5N1 virulence by directly
      affecting the virus itself, (b) inhibit H5N1 viral replication by maintaining
      cellular redox equilibrium in host cells, (c) inhibit H5N1 replication by a
      blockade of the nuclear-cytoplasmic translocation of the viral ribonucleoproteins
      and reduced expression of late viral proteins related to the inhibition of
      protein kinase C activity and its dependent pathways, (d) down-regulate
      activation and proliferation of proinflammatory cytokines in respiratory
      epithelial cells and macrophages that are implicated in the pathogenesis of H5N1
      influenza, and (e) protect the lungs and other vital organs from virus- and
      cytokine-induced oxidative stress by supplying and maintaining sufficient levels
      of exogenous and endogenous antioxidants. Key mediators in these processes
      include selenium, vitamin E, NAC/glutathione, resveratrol, and quercetin. Taken
      prophylactically, and throughout the duration and recovery of an H5N1 infection,
      the nutritional supplement formula may aid humans infected with H5N1 influenza to
      survive with a reduced likelihood of major complications, and may provide a
      relatively low-cost strategy for individuals as well as government, public
      health, medical, health-insurance, and corporate organizations to prepare more
      prudently for an H5N1 pandemic. Some evidence also indicates that the supplement
      formulation may be effective as an adjunctive to H5N1 vaccine and anti-viral
      treatments, and should be tested as such.

PMID- 16624497
TI  - Physiology of long pranayamic breathing: neural respiratory elements may provide
      a mechanism that explains how slow deep breathing shifts the autonomic nervous
      system.
AB  - Pranayamic breathing, defined as a manipulation of breath movement, has been
      shown to contribute to a physiologic response characterized by the presence of
      decreased oxygen consumption, decreased heart rate, and decreased blood pressure,
      as well as increased theta wave amplitude in EEG recordings, increased
      parasympathetic activity accompanied by the experience of alertness and
      reinvigoration. The mechanism of how pranayamic breathing interacts with the
      nervous system affecting metabolism and autonomic functions remains to be clearly
      understood. It is our hypothesis that voluntary slow deep breathing functionally
      resets the autonomic nervous system through stretch-induced inhibitory signals
      and hyperpolarization currents propagated through both neural and non-neural
      tissue which synchronizes neural elements in the heart, lungs, limbic system and
      cortex. During inspiration, stretching of lung tissue produces inhibitory signals
      by action of slowly adapting stretch receptors (SARs) and hyperpolarization
      current by action of fibroblasts. Both inhibitory impulses and hyperpolarization
      current are known to synchronize neural elements leading to the modulation of the
      nervous system and decreased metabolic activity indicative of the parasympathetic
      state. In this paper we propose pranayama's physiologic mechanism through a
      cellular and systems level perspective, involving both neural and non-neural
      elements. This theoretical description describes a common physiological mechanism
      underlying pranayama and elucidate the role of the respiratory and cardiovascular
      system on modulating the autonomic nervous system. Along with facilitating the
      design of clinical breathing techniques for the treatment of autonomic nervous
      system and other disorders, this model will also validate pranayama as a topic
      requiring more research.

PMID- 16624498
TI  - Apoptotic cell death and cardiovascular diseases; clinical implications.

PMID- 16624499
TI  - Is tinnitus useful in early detection of incoming heart decompensation?
AB  - In previous studies the possibility of a mechanism of hemodynamic imbalance
      consequent to a sharp decrease in blood pressure causing a more or less transient
      inner ear impairment was evaluated and to some extent demonstrated. In this
      scenario, tinnitus is very frequently present as a debilitating symptom
      associated to cochlear impairment. On the other hand, a possible cause of a sharp
      decrease in blood pressure is represented by major cardiovascular disorders,
      requiring an early assessment in order to avoid fatal consequences. In this
      paper, the hypothesis of resorting to tinnitus as a simple warning method for
      self detecting a possibly incoming cardiovascular imbalance in patients with
      heart failure (HF) is advanced.

PMID- 16624500
TI  - The chaotic nature of temper in humans: a long short-term memory recurrent neural
      network model.
AB  - In mathematics and physics, chaos theory deals with the behavior of certain
      nonlinear dynamical systems that under certain conditions exhibit a phenomenon
      known as chaos, which is characterised by a sensitivity to initial conditions.
      Mathematicians paradoxically call such states of order chaos and distinguish them
      from randomness. New models for describing and predicting different aspects of
      behavior are being created which once seemed unpredictable. This is done by
      focusing on the overall patterns of behavior, showing how stable or unstable they
      are and identifying the circumstances that make them change. In this paper, we
      indicate why human temper and mood changes have a chaotic nature. Then, we
      develop a chaotic model based on a long short-term memory recurrent neural
      network with irregular embeddings derived by the gamma test to model temper
      tantrum. We finally use a feedback delay controller to stabilize its chaotic
      behavior, because it is a plausible method for stabilizing biological neural
      systems. A lot of aspects of this model are analogous to the human counterpart.
      The model might suggest, for example, that if a particular person had stronger
      ego defenses, and attended a little less vigilantly to the external world, he or
      she might find a stable attractor amidst of a broader landscape of chaotic
      attractors. A therapist or self-control would be analogous to the delayed
      feedback controller, by specifically encouraging those changes, he might help the
      person reach a stable behavior. Finally, some comments are proposed to facilitate
      the normal behavior.

PMID- 16624501
TI  - Arthropod repellency, especially tick (Ixodes ricinus), exerted by extract from
      Artemisia abrotanum and essential oil from flowers of Dianthus caryophyllum.
AB  - A toluene extract of southernwood (Artemisia abrotanum) and the essential oil
      from flowers of carnation (Dianthus caryophyllum ) exerted pronounced a repellent
      effect both against ticks (nymphs of Ixodes ricinus) and yellow fever mosquitoes
      (Aedes aegypti). The most potent repellents found were coumarin and thujyl
      alcohol from A. abrotanum and phenylethanol from D. caryophyllum where coumarin
      and thujyl alcohol were also detected.

PMID- 16624502
TI  - On the phylogenetic position of a rare Iberian endemic mammal, the Pyrenean
      desman (Galemys pyrenaicus).
AB  - The nucleotide sequences of the complete mitochondrial genome and nine partial
      nuclear genes of the Pyrenean desman (Galemys pyrenaicus) were determined in
      order to establish the relative phylogenetic position of this species at
      different taxonomic levels within the placental tree. Phylogenetic relationships
      of desman within the family Talpidae were inferred based on complete
      mitochondrial cytochrome b gene nucleotide sequence data. The Pyrenean desman was
      unambiguously recovered as sister group of the Russian desman (Desmana moschata)
      confirming the monophyly of the subfamily Desmaninae. However, phylogenetic
      relationships among major lineages within the Talpidae could not be confidently
      resolved. Phylogenetic analyses based on mitochondrial (at the amino acid level)
      and nuclear (at the nucleotide level) sequence data sets confidently placed
      desman within the Eulipotyphla (that also included moles, shrews, and hedgehogs),
      and partially recovered placental interordinal relationships. The monophyly of
      Laurasiatheria (including Eulipotyphla, Chiroptera, Carnivora, Pholidota,
      Perissodactyla, and Cetartiodactyla) was strongly supported. Mitochondrial amino
      acid sequences of Pholidota (pangolins) were found to bias phylogenetic
      inferences due to long-branch attraction effects. A Bayesian inference based on a
      combined mitochondrial and nuclear data set without Pholidota arrived at an
      almost fully resolved tree that supported the basal position of Eulipotyphla
      within Laurasiatheria.

PMID- 16624503
TI  - The mitochondrial tRNA(Thr) A15951G mutation may influence the phenotypic
      expression of the LHON-associated ND4 G11778A mutation in a Chinese family.
AB  - We report here the characterization of a three-generation Han Chinese family with
      Leber's hereditary optic neuropathy (LHON). This Chinese family exhibited high
      penetrance and expressivity of visual impairment. The average age-of-onset was 19
      years in this family. All male and 33% female matrilineal relatives in this
      Chinese family developed visual loss with a wide range of severity, ranging from
      blindness to normal vision. Sequence analysis of the complete mitochondrial DNA
      in this pedigree revealed the presence of the ND4 G11778A mutation and 40 other
      variants, belonging to the Asian haplogroup D4. The G11778A mutation is present
      at homoplasmy in matrilineal relatives of this Chinese family. Of other variants,
      the homoplasmic A15951G mutation is of special interest as it is located adjacent
      to 3' end, at conventional position 71 of tRNA(Thr). The adenine (A71) at this
      position of tRNA(Thr), highly conserved from bacteria to human mitochondria, has
      been implicated to be important for tRNA identity and pre-tRNA processing. In
      fact, the significant reduction of the steady-state levels in tRNA(Thr) was
      observed in cells carrying both the A15951G and G11778A mutations but not cells
      carrying only G11778A mutation. Thus, the A15951G mutation most probably leads to
      a failure in mitochondrial tRNA metabolism, worsening the mitochondrial
      dysfunction associated with the primary G11778A mutation. These imply that the
      tRNA(Thr) A15951G mutation may have a potential modifier role in increasing the
      penetrance and expressivity of the primary LHON-associated G11778A mutation in
      this Chinese family.

PMID- 16624504
TI  - Molecular characterization of the porcine deleted in malignant brain tumors 1
      gene (DMBT1).
AB  - The human gene deleted in malignant brain tumors 1 (DMBT1) is considered to play
      a role in tumorigenesis and pathogen defense. It encodes a protein with multiple
      scavenger receptor cysteine-rich (SRCR) domains, which are involved in
      recognition and binding of a broad spectrum of bacterial pathogens. The SRCR
      domains are encoded by highly homologous repetitive exons, whose number in humans
      may vary from 8 to 13 due to genetic polymorphism. Here, we characterized the
      porcine DMBT1 gene on the mRNA and genomic level. We assembled a 4.5 kb porcine
      DMBT1 cDNA sequence from RT-PCR amplified seminal vesicle RNA. The porcine DMBT1
      cDNA contains an open reading frame of 4050 nt. The transcript gives rise to a
      putative polypeptide of 1349 amino acids with a calculated mass of 147.9 kDa.
      Compared to human DMBT1, it contains only four N-terminal SRCR domains. Northern
      blotting revealed transcripts of approximately 4.7 kb in size in the tissues
      analyzed. Analysis of ESTs suggested the existence of secreted and transmembrane
      variants. The porcine DMBT1 gene spans about 54 kb on chromosome 14q28-q29. In
      contrast to the characterized cDNA, the genomic BAC clone only contained 3 exons
      coding for N-terminal SRCR domains. In different mammalian DMBT1 orthologs large
      interspecific differences in the number of SRCR exons and utilization of the
      transmembrane exon exist. Our data suggest that the porcine DMBT1 gene may share
      with the human DMBT1 gene additional intraspecific variations in the number of
      SRCR-coding exons.

PMID- 16624505
TI  - Molecular genotyping of Salmonella enterica Abortusovis by pulsed field gel
      electrophoresis.
AB  - Genotyping of Salmonella strains is an important tool to discriminate among
      isolates and to improve epidemiological studies when an outbreak occurs. No
      phagetyping scheme is available for Salmonella enterica subsp. enterica serovar
      Abortusovis (SAO) and molecular methods previously used were not standardized and
      were time consuming. Among the DNA-based methods of genotyping, pulsed field gel
      electrophoresis (PFGE) is currently in use to subtype Salmonella isolates. In
      this study we evaluated the feasibility of genotyping of SAO by XbaI and BlnI
      restrictions. Separation of restricted fragments was performed by PFGE. To test
      the possibility to apply this methodology to epidemiological investigation, a
      collection of 38 SAO strains isolated in different regions of Italy were
      analyzed. Eighteen and 29 different PFGE profiles were defined for XbaI and BlnI
      digestions, respectively. The method demonstrated an adequate typing ability and
      an excellent discriminatory power. Results from this study show that PFGE may
      represent a powerful tool to discriminate within the SAO serovar, and provide
      useful information in support of traditional epidemiological investigations. In
      particular, this method could be used to identify the origin of infection during
      outbreaks within a single flock or in different herds.

PMID- 16624506
TI  - Effects of the anti-neoplastic agent ET-18-OCH3 and some analogs on the
      biophysical properties of model membranes.
AB  - The effect of 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OCH(3),
      edelfosine), and six other analog asymmetric phosholipids on the physical
      properties of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) model membranes
      was studied using differential scanning calorimetry (DSC), (31)P-nuclear magnetic
      resonance ((31)P NMR) and X-ray diffraction. DSC data revealed that, at
      concentrations of 40mol% and higher, a new type of mixtures with higher T(c) and
      narrower transitions appeared with all the asymmetric lipids studied. At very
      high concentrations of these lipids (50-80 mol%), destabilization was observed in
      the systems probably because of the formation of micelles or small vesicles. In
      all cases, the asymmetric lipids at concentrations of 40 mol% induced the
      formation of interdigitated structures in the lamellar gel phase, as deduced from
      X-ray diffraction. The asymmetric phospholipids were also added to 1,2-dielaidoyl
      sn-glycero-3-phosphoethanolamine (DEPE) model membranes and DSC data revealed
      that the lipids primarily affected transition from the lamellar gel (L(beta)) to
      the lamellar liquid crystalline (L(alpha)) phase in two aspects: the transition
      temperature was reduced, and the transition itself became broader and smaller.
      The lamellar liquid crystalline (L(alpha)) to inverted hexagonal phase (H(II))
      transition was also affected, as detected by DSC and (31)P NMR data. Increasing
      concentrations of the asymmetric lipids reduced the formation of inverted
      hexagonal phases, which were completely inhibited in the case of ET-18-OCH(3).
      Since these compounds have been shown to have important biological actions
      through the plasma membrane, these results may help to understand the mechanism
      of action of these compounds. In addition these asymmetric lipids were tested for
      their capacity to induce cell apoptosis, and only ET-18-OCH(3) was found to have
      a clear effect, thus suggesting that the apoptotic effect is not exerted through
      changes in the biophysical properties of model membranes.

PMID- 16624507
TI  - Preparation and properties of poly(vinyl alcohol)-stabilized liposomes.
AB  - The purpose of this work is to evaluate the improvement in physical stability of
      poly(vinyl alcohol) (PVA) modified liposomes. Liposomes composed of soya
      phosphatidylcholile (SPC) and cholesterol (1:1 molar ratio) were prepared by
      reverse phase evaporation method. Two types of interaction between liposome and
      PVA were investigated: PVA addition into lipid bilayer during liposome
      preparation and coating of already formed liposomes with PVA. The microparticles
      system was morphologically characterized by transmission electron microscopy
      (TEM) and particles analysis. Changes in particles size and zeta potential
      confirmed the existence of a thick polymer layer on the surface of liposomes. The
      amount of PVA adsorbing to liposomes and the encapsulation efficiency increased
      with increasing polymer concentration. The physical stability was evaluated by
      measuring the release rate of contents at 20 and 37 degrees C, the PVA modified
      liposomes were more stable than the conventional liposomes. Comparing with PVA
      coated liposomes, the liposomes with PVA addition to the bilayer were more
      stable, and had higher entrapment efficiency.

PMID- 16624508
TI  - In vitro evaluation of the effect of cyclodextrin complexation on pulmonary
      deposition of a peptide, cyclosporin A.
AB  - The effect of hydroxypropyl-alpha-cyclodextrin (HP-alpha-CD) complexation on in
      vitro pulmonary deposition of a cyclic peptide cyclosporin A (CsA) was studied.
      In addition, the effect of storage (32 days, 40 degrees C, 75% RH) on CsA/HP
      alpha-CD complexes was studied. The complexation of CsA with CDs was evaluated by
      a phase-solubility method. Solid CsA/HP-alpha-CD complexes were prepared by
      freeze drying. Three inhalation formulations were prepared: CsA/lactose reference
      formulation (LF) (drug:carrier 1:364, w/w), CsA/HP-alpha-CD complex formulation
      (CDF) (drug:CD 1:269, w/w) and CsA/HP-alpha-CD complex/lactose formulation (CDLF)
      (complex:carrier 100:114, w/w). The inhalation studies were performed in vitro
      using Andersen Sampler (Ph. Eur.) and Taifun multi-dose dry powder inhalers
      (DPIs). Before the storage, the respirable fraction value (RF%) of CsA was 19.8+/
      0.7%, 33.0+/-7.0% and 34.6+/-1.1% (mean+/-S.D., n=4 x 20) with LF, CDF and CDLF,
      respectively. When exposed to moisture (storage in a permeable polystyrene tube),
      the RF% values of CsA from formulations containing CsA/HP-alpha-CD complexes were
      lower than before the storage. However, when stored in the Taifun DPI, the RF%
      value of CsA from any of the formulations did not decrease. In conclusion, an
      acceptable RF% value of a peptide CsA from freeze-dried, simply micronized CsA/HP
      alpha-CD complex powder was achieved before and after storage in the DPI.

PMID- 16624509
TI  - Characterization of biodegradable chitosan microspheres containing vancomycin and
      treatment of experimental osteomyelitis caused by methicillin-resistant
      Staphylococcus aureus with prepared microspheres.
AB  - The biodegradable chitosan microspheres containing vancomycin hydrochloride
      (VANCO) were prepared by spray drying method with different polymer:drug ratios
      (1:1, 2:1, 3:1 and 4:1). Thermal behaviour, particle size and distribution,
      morphological characteristics, drug content, encapsulation efficiency, in vitro
      release assessments of formulations have been carried out to obtain suitable
      formulation which shows sustained-release effect when implanted. Sterilized VANCO
      loaded microspheres were implanted to proximal tibia of rats with methicillin
      resistant Staphylococcus aureus (MRSA) osteomyelitis. Intramuscular (IM)
      injection of VANCO for 21 days was applied to another group for comparison. After
      3 weeks of treatment, bone samples were analysed with a microbiological assay.
      According to the results, encapsulation efficiency and yield of microspheres in
      all formulations were higher than 98% and 47%, respectively. Particle sizes of
      microspheres were smaller than 6 microm. All microsphere formulations have shown
      sustained-release effect. In vitro drug release rate decreased due to the
      increase in polymer:drug ratio but no significant difference was seen between
      these results (p>0.05). Based on our in vivo data, rats implanted VANCO-loaded
      chitosan microspheres and administered IM injection showed 3354+/-3366 and
      52500+/-25635 colony forming unit of MRSA in 1g bone samples (CFU/g),
      respectively. As a result, implanted VANCO-loaded microspheres were found to be
      more effective than IM route for the treatment of experimental osteomyelitis.

PMID- 16624510
TI  - Spiral ganglion cell site of excitation II: numerical model analysis.
AB  - An anatomically based model of cochlear neuron electrophysiology has been
      developed and used to interpret the physiological responses of the auditory
      neuron to electrical summation and refractory pulse-pair stimuli. For summation
      pulses, the summation time constant, tau(sum), indicates the ability of the
      membrane to hold charge after cessation of a pulse. When a spiral ganglion cell
      with a cell body was simulated, the value of tau(sum) was elevated at the
      peripheral node adjacent to the cell body. For refraction pulses, the refraction
      time constant, tau(ref), indicates the duration of the relative refractory period
      of the membrane. In spiral ganglion cell simulations, tau(ref) was decreased at
      the peripheral node adjacent to the cell body and slightly elevated at other
      peripheral nodes. The extent of the cell body influence on tau(sum) and tau(ref)
      was high localized. Excitation times for the nodes adjacent to the cell body were
      either simultaneous or near simultaneous resulting in similar response latencies.
      Results indicate that values of tau(sum) and tau(ref) may be useful for
      distinguishing central and peripheral excitation sites while latency measures
      alone are not a good indication of site of excitation.

PMID- 16624511
TI  - Spiral ganglion cell site of excitation I: comparison of scala tympani and
      intrameatal electrode responses.
AB  - To determine the site of excitation on the spiral ganglion cell in response to
      electrical stimulation similar to that from a cochlear implant, single-fiber
      responses to electrical stimuli delivered by an electrode positioned in the scala
      tympani were compared to responses from stimuli delivered by an electrode placed
      in the internal auditory meatus. The response to intrameatal stimulation provided
      a control set of data with a known excitation site, the central axon of the
      spiral ganglion cell. For both intrameatal and scala tympani stimuli, the
      responses to single-pulse, summation, and refractory stimulus protocols were
      recorded. The data demonstrated that summation pulses, as opposed to single
      pulses, are likely to give the most insightful measures for determination of the
      site of excitation. Single-fiber summation data for both scala tympani and
      intrameatally stimulated fibers were analyzed with a clustering algorithm.
      Combining cluster analysis and additional numerical modeling data, it was
      hypothesized that the scala tympani responses corresponded to central excitation,
      peripheral excitation adjacent to the cell body, and peripheral excitation at a
      site distant from the cell body. Fibers stimulated by an intrameatal electrode
      demonstrated the greatest range of jitter measurements indicating that greater
      fiber independence may be achieved with intrameatal stimulation.

PMID- 16624512
TI  - Specific plasticity responses to unilaterally decreased or increased hearing
      intensity in the adult cochlear nucleus and beyond.
AB  - Variations of sensory activation in strength and pattern are known to affect
      structure and function of the mammalian brain. Whereas such malleability is
      readily granted to forebrain structures at early developmental stages, acceptance
      of experience-dependent structural plasticity has been slow for the adult
      brainstem. Over the past years we have identified consequences of cochlear
      ablation, noise trauma, or electrical intracochlear stimulation on neurons and
      circuitry of the auditory brainstem of the adult rat. We found that loss of
      sensory activation as well as a substitution for it entail specific molecular,
      ultrastructural, and morphological changes to central auditory neurons. Here, we
      make a first attempt to compare these different patterns of central remodeling.
      We tentatively suggest that after hearing loss or intracochlear stimulation
      responses of the central neural network in the adult brainstem suit the concept
      of functional adaptation.

PMID- 16624513
TI  - Studies on the reproductive, cytological and biochemical toxicity of Ginkgo
      Biloba in Swiss albino mice.
AB  - Ginkgo biloba (an herbal product), used as a folkloric medicine in the treatment
      of dementia, was evaluated for its effects on reproductive, cytological and
      biochemical toxicity in male Swiss albino mice. The mice were treated with
      different doses (25, 50 and 100mg/kg/day) of the aqueous suspension of Ginkgo
      biloba for 90 days by oral gavage. The following parameters were evaluated: (1)
      reproductive organ weight; (2) motility and content of sperms; (3) spermatozoa
      morphology; (4) cytology of the testes chromosomes; (5) study on reproduction;
      (6) biochemical study on proteins, nucleic acids, malondialdehyde (MDA) and
      nonprotein sulfhydryl (NP-SH). The treatment caused significant changes in the
      weight of caudae epididymis, prostate, chromosomal aberrations, rate of pregnancy
      and pre-implantation loss. However, the percent motility, sperm count and
      morphology of spermatozoa were not affected. Our study on biochemical parameters
      showed depletion of nucleic acids, NP-SH and increase of MDA, which elucidated
      the role of free radical species in the induced changes in testis chromosomes and
      the reproductive function. The exact mechanism is not known, however, the
      activation of GABA, glycine and glutamate under the influence of Ginkgo biloba
      and its constituents might have generated free radicals and depleted cellular
      glutathione by calcium influx and membrane depolarization. The observed toxicity
      is attributed to the toxic constituents (ginkgolic acids, biflavones, cardanols,
      cardols, bilobalides and quercetin) of Ginkgo biloba. Our results warrant careful
      use of Ginkgo biloba as a remedy for impotence and/or erectile dysfunction.

PMID- 16624514
TI  - Tissue-specific deletion patterns of the mitochondrial genome with advancing age.
AB  - Aging is a multifactorial process and a lot of theories have been put forward to
      explain the deterioration of organ function with advancing age. The free radical
      hypothesis developed by Harman is amongst the most prominent today and has been
      focused on mitochondrial aging in the last decades. Applying a long PCR approach
      we screened human skeletal muscle, heart, caudate nucleus and cerebellum of 50
      individuals for large-scale deletions of mitochondrial DNA (mtDNA). The most
      important observation of our study was the detection of age dependent tissue
      specific deletion patterns of mtDNA. The pattern of the same tissue of different
      individuals was more similar than the pattern of different tissues of the same
      individuals. Whereas deletions were barely detectable in cerebellar tissue, in
      caudate nucleus a specific banding pattern with deletions of 4-8 kb was already
      observed around the age of thirty. However, the increase of these large-scale
      deletions in number and variety over lifetime was more pronounced in skeletal
      muscle or heart. Our data support the notion that different tissues accumulate
      mtDNA damage in a specific manner. Although functional consequences of
      mitochondrial deletions are clearly supported by experimental data on the single
      cell level in model organisms and mammals, their role regarding impaired function
      of organs with advancing age in humans remains unresolved.

PMID- 16624515
TI  - Molecular identification and differentiation of Brevibacterium species and
      strains.
AB  - Amplified ribosomal DNA restriction enzyme analysis (ARDRA), pulsed field gel
      electrophoresis (PFGE) and ribotyping were used to differentiate among 24 strains
      of Brevibacterium linens, Brevibacterium casei and Brevibacterium epidermidis
      obtained from type culture collections or isolated from various smear ripened
      cheeses. ARDRA was applied to the 16S rDNA. B. linens was shown to be a quite
      heterogenic group with 2 to at least 4 copies of rrn operons per strain with
      aberrant nucleotide sequences. AccI gave genus specific restriction patterns and
      was used to separate Brevibacterium from Corynebacterium species. The expected
      species specificity of TaqI applied to B. linens type culture strains, but not to
      all strains isolated from cheese. By AvaI restriction, B. casei and B. linens
      were differentiated from B. epidermidis and the orange pigmented Arthrobacter
      casei, a new species of coryneform bacteria; by XmnI restriction, B. linens and
      B. epidermidis were differentiated from B. casei. One of 4 B. linens genotypes
      could not be distinguished from B. casei by this method. Here, the typical orange
      B. linens pigments were used for classification, which was confirmed by partial
      sequencing of the 16S rDNA.

PMID- 16624516
TI  - High-density mapping and comparative analysis of agronomically important traits
      on wheat chromosome 3A.
AB  - Bread wheat chromosome 3A has been shown to contain genes/QTLs controlling grain
      yield and other agronomic traits. The objectives of this study were to generate
      high-density physical and genetic-linkage maps of wheat homoeologous group 3
      chromosomes and reveal the physical locations of genes/QTLs controlling yield and
      its component traits, as well as agronomic traits, to obtain a precise estimate
      of recombination for the corresponding regions and to enrich the QTL-containing
      regions with markers. Physical mapping was accomplished by 179 DNA markers mostly
      representing expressed genes using 41 single-break deletion lines. Polymorphism
      survey of cultivars Cheyenne (CNN) and Wichita (WI), and a substitution line of
      CNN carrying chromosome 3A from WI [CNN(WI3A)], with 142 RFLP probes and 55 SSR
      markers revealed that the extent of polymorphism is different among various group
      3 chromosomal regions as well as among the homoeologs. A genetic-linkage map for
      chromosome 3A was developed by mapping 17 QTLs for seven agronomic traits
      relative to 26 RFLP and 15 SSR chromosome 3A-specific markers on 95 single
      chromosome recombinant inbred lines. Comparison of the physical maps with the 3A
      genetic-linkage map localized the QTLs to gene-containing regions and accounted
      for only about 36% of the chromosome. Two chromosomal regions containing 9 of the
      17 QTLs encompassed less than 10% of chromosome 3A but accounted for almost all
      of the arm recombination. To identify rice chromosomal regions corresponding to
      the particular QTL-containing wheat regions, 650 physically mapped wheat group 3
      sequences were compared with rice genomic sequences. At an E value of E < or =
      10(-5), 82% of the wheat group 3 sequences identified rice homologs, of which 54%
      were on rice chromosome 1. The rice chromosome 1 region collinear with the two
      wheat regions that contained 9 QTLs was about 6.5 Mb.

PMID- 16624517
TI  - Gain of imprinting of SLC22A18 sense and antisense transcripts in human breast
      cancer.
AB  - The 11p15.5 region harbors three imprinted sense/antisense transcript pairs,
      SLC22A18/SLC22A18AS, IGF2/IGF2AS (PEG8), and KCNQ1/KCNQ1OT1 (LIT1). SLC22A18
      (solute carrier family 22 (organic cation transporter) member 18) and its
      antisense transcript SLC22A18AS are paternally suppressed in fetal samples. In
      adult tissue, SLC22A18 displays polymorphic imprinting, but the imprinting status
      of SLC22A18AS remains elusive. SLC22AI8 DNA-PCR-RFLP analysis using NlaIII
      restriction digestion identified SLC22A18 heterozygotes within this breast tissue
      cohort (n = 89). Commercial sequencing identified informative SLC22A18AS samples.
      Random hexamer-primed cDNA synthesis, SLC22A18/SLC22A18AS-specific PCR, and
      imprinting evaluation by commercial sequencing demonstrated that SLC22A18AS
      displays a nonimprinted profile in reduction mastectomies (n = 6). However,
      SLC22A18 showed a gain of imprinting (GOI) in 1/4 of these normal cases. In the
      malignant cohort, GOI was also demonstrated in 18% for SLC22A18 and 14% for
      SLC22A18AS, occurring concomitantly in one case. This study reports the
      imprinting status of SLC22A18AS in adult tissue, and shows that GOI affects both
      the sense, and antisense transcripts at this locus in human breast tissue.

PMID- 16624518
TI  - Accurate and precise transcriptional profiles from 50 pg of total RNA or 100 flow
      sorted primary lymphocytes.
AB  - We have developed a total RNA amplification and labeling strategy for use with
      Affymetrix GeneChips. Our protocol, which we denote BIIB, employs two rounds of
      linear T7 amplification followed by Klenow labeling to generate a biotinylated
      cDNA. In benchmarking studies using a titration of mouse universal total RNA,
      BIIB outperformed commercially available kits in terms of sensitivity, accuracy,
      and amplified target length, while providing equivalent results for technical
      reproducibility. BIIB maintained 50 and 44% present calls from 100 and 50 pg of
      total RNA, respectively. Inter- and intrasample precision studies indicated that
      BIIB produces an unbiased and complete expression profile within a range of 5 ng
      to 50 pg of starting total RNA. From a panel of spiked exogenous transcripts, we
      established the BIIB linear detection limit to be 20 absolute copies.
      Additionally, we demonstrate that BIIB is sensitive enough to detect the
      stochastic events inherent in a highly diluted sample. Using RNA isolated from
      whole tissues, we further validated BIIB accuracy and precision by comparison of
      224 expression ratios generated by quantitative real-time PCR. The utility of our
      method is ultimately illustrated by the detection of biologically expected trends
      in a T cell/B cell titration of 100 primary cells flow sorted from a healthy
      mouse spleen.

PMID- 16624519
TI  - A microsatellite-based genetic linkage map of the waterflea, Daphnia pulex: On
      the prospect of crustacean genomics.
AB  - We describe the first genetic linkage map for Daphnia pulex using 185
      microsatellite markers, including 115 new markers reported in this study. Our
      approach was to study the segregation of polymorphisms in 129 F2 progeny of one
      F1 hybrid obtained by crossing two genetically divergent lineages of Daphnia
      isolated from two Oregon populations. The map spanned 1206 Kosambi cM and had an
      average intermarker distance of 7 cM. Linkage groups ranged in size from 7 to 185
      cM and contained 4 to 27 markers. The map revealed 12 linkage groups
      corresponding to the expected number of chromosomes and covers approximately 87%
      of the genome. Tests for random segregation of alleles at individual loci
      revealed that 21% of the markers showed significant transmission ratio distortion
      (primarily homozygote deficiency) likely due to markers being linked to
      deleterious recessive alleles. This map will become the anchor for the physical
      map of the Daphnia genome and will serve as a starting point for mapping single
      and quantitative trait loci affecting ecologically important phenotypes. By
      mapping 342 tentative orthologous gene pairs (Daphnia/Drosophila) into the
      Daphnia linkage map, we facilitate future comparative projects.

PMID- 16624520
TI  - Effect of early lead exposure on the maturation of children's postural balance: a
      longitudinal study.
AB  - This prospective study investigated the impact of early exposure to lead on the
      maturation of children's postural balance. The effect of lead exposure on age
      associated maturation of postural balance was investigated on 91 children from
      the Cincinnati Lead Study (CLS) with a 5-year geometric mean lead concentration
      in blood of 11.66 microg/dL (range 3.89-28.33 microg/dL) by re-assessing their
      postural balance approximately every 20 months starting at mean age of 6.6 years
      through mean age of 12.1 years. The results presented in this paper provide
      evidence that low to moderate lead exposure in early childhood has a measurable
      and statistically significant impact on the maturation of postural balance. In
      comparison to less exposed children, of those in the higher lead group showed an
      impaired postural balance response. The results from this study suggest that
      children with early childhood lead exposure may need additional time to approach
      (or "catch up" with) their maturational postural balance status. As these
      subjects are now adults in their early to mid-twenties, poor postural balance may
      impact their daily living tasks and pose a higher risk of potential injuries at
      home and work.

PMID- 16624521
TI  - Parallel and distributed neural models of the ideomotor principle: an
      investigation of imitative cortical pathways.
AB  - Humans' capacity to imitate has been extensively investigated through a wide
      range of behavioral and developmental studies. Yet, despite the huge amount of
      phenomenological evidence gathered, we are still unable to relate this behavioral
      data to any specific neural substrate. In this paper, we investigate how
      principles from psychology can be the result of neural computations and therefore
      attempt to bridge the gap between monkey neurophysiology and human behavioral
      data, and hence between these two complementary disciplines. Specifically, we
      address the principle of ideomotor compatibility, by which 'observing the
      movements of others influences the quality of one's own performance' and develop
      two neural models which account for a set of related behavioral studies [Brass,
      M., Bekkering, H., Wohlschlager, A., & Prinz, W. (2000). Compatibility between
      observed and executed finger movements: comparing symbolic, spatial and imitative
      cues. Brain and Cognition 44, 124-143]. We show that the ideomotor effect could
      be the result of two distinct cognitive pathways, which can be modeled by means
      of biologically plausible neural architectures. Furthermore, we propose a novel
      behavioral experiment to confirm or refute either of the two model pathways.

PMID- 16624522
TI  - Intermuscular cavernous lymphangioma presenting with overgrowth of fat: MRI
      findings.
AB  - We present a case of an intermuscular cavernous lymphangioma with predominantly
      composed of fatty tissue. A 58-year-old man complained a palpable painless mass
      over his right arm for 1 month. Magnetic resonance imaging (MRI) showed a 14-cm
      mass with predominantly composed of fatty tissue between long and short heads of
      triceps muscle. There were some serpiginous structures with hyperintensity within
      the tumors on gradient-echo and gadolinium enhanced T1-weighted images.
      Histologic examination revealed a picture of intermuscular angioma predominantly
      composed of cavernous lymphangioma.

PMID- 16624524
TI  - Region-specific loss of zinc in the brain in pentylentetrazole-induced seizures
      and seizure susceptibility in zinc deficiency.
AB  - The hippocampus is thought to be an epileptic focus in human temporal lobe
      epilepsy. Kainate-induced seizures decrease zinc concentrations in the
      hippocampus, which is also decreased in young mice fed a zinc-deficient diet for
      4 weeks, and is enhanced by zinc deficiency. To understand zinc movement in the
      brain in epileptic seizures, zinc concentrations in the brain were measured in
      young mice after administration of pentylentetrazole, a GABAA receptor
      antagonist. Zinc concentration in the hippocampus and Timm's stain, with which
      histochemically reactive zinc in the presynaptic vesicle is detected, were
      decreased after the administration, suggesting that excessive excitation of zinc
      containing glutamatergic neurons is induced in the hippocampus with
      pentylentetrazole. To clarify whether the decrease in zinc concentration in the
      hippocampus in zinc deficiency alter seizure susceptibility, furthermore,
      susceptibility to pentylentetrazole-induced seizures was examined in young mice
      fed the zinc-deficient diet for 4 weeks. The susceptibility, unlike
      susceptibility to kainate-induced seizures, was not appreciably enhanced by zinc
      deficiency. These results suggest that the decrease in zinc concentration in the
      hippocampus in zinc deficiency does not influence susceptibility to
      pentylentetrazole-induced seizures.

PMID- 16624523
TI  - TRIP6 transcriptional co-activator is a novel substrate of AMP-activated protein
      kinase.
AB  - AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that
      acts as a sensor of cellular energy charge. Once activated it switches on
      catabolic pathways and switches off many ATP-consuming processes (anabolic
      pathways) to preserve the energy status of the cell. In order to identify new
      targets of AMPK action we have performed a two-hybrid screening of a human
      pancreas cDNA library. As a result, we have identified TRIP6 as a novel target of
      AMPK action. This protein belongs to the zyxin family of proteins located at the
      focal adhesion plaques in the plasma membrane, although they may also travel to
      the nucleus, where they have regulatory properties. We confirmed the physical
      interaction between the catalytic subunit (AMPK-alpha2) of the AMPK complex and
      TRIP6 in mammalian cells by two-hybrid and co-immunoprecipitation assays. We also
      showed that AMPK was able to phosphorylate in vitro TRIP6 at the N-terminus.
      Finally, we present evidence that transcriptional co-activator properties of
      TRIP6 were enhanced by AMPK action.

PMID- 16624525
TI  - Shift-back of right into left hemisphere language dominance after control of
      epileptic seizures: evidence for epilepsy driven functional cerebral
      organization.
AB  - Atypical, i.e. right hemisphere language dominance is frequently observed in
      early onset left hemisphere epilepsies. In left mesial temporal lobe epilepsy,
      where eloquent cortex is not directly involved, it is a matter of debate, to
      which degree atypical language dominance is driven not only by morphological
      lesions but also by epileptic dysfunction, and whether atypical dominance is
      hardwired or not. Taking this as the background this study evaluated the
      hypothesis that epilepsy driven atypical dominancy might be reversible when
      seizures are successfully controlled. This was evaluated in patients with left
      mesial temporal lobe epilepsy, who were atypically language dominant by means of
      language fMRI before surgery, and became seizure free after left selective
      amygdalo-hippocampectomy. Three out of 53 consecutive atypically dominant
      patients with chronic epilepsy fulfilled these criteria. Postoperative follow-up
      language fMRI indicated reversal of right into left dominance in one patient
      going along with unexpected losses in verbal memory performance. The two other
      patients experienced unchanged or even enhancement of the pre-existing dominance
      pattern, going along with consistent postoperative performance changes in
      cognition. The data thus provide supporting evidence that atypical language
      dominance can indeed be functionally driven and moreover that in at least some
      patients, right hemispheric language can shift-back to the left hemisphere when
      the driving factor, i.e. seizures, becomes successfully controlled. The results
      have clinical implications for outcome prediction after brain surgery in
      atypically dominant patients with epilepsy. However, further research in larger
      groups of atypically dominant patients is required to identify the conditions
      under which atypical dominance becomes hardwired and when not.

PMID- 16624526
TI  - Genetic and expression analyses of the STOP (MAP6) gene in schizophrenia.
AB  - Accumulating evidence suggests that the pathologic lesions of schizophrenia may
      in part be due to the altered cytoskeletal architecture of neurons. Microtubule
      associated proteins (MAPs) that bind to cytoskeletal microtubules to stabilize
      their assembly are prominently expressed in neurons. Of the MAPs, MAP6 (STOP) has
      a particular relevance to schizophrenia pathology, since mice deficient in the
      gene display neuroleptic-responsive behavioral defects. Here we examined the
      genetic contribution of MAP6 to schizophrenia in a case (n = 570) -control (n =
      570) study, using dense single nucleotide polymorphism (SNP) markers. We detected
      nominal allelic (p = 0.0291) and haplotypic (global p = 0.0343 for 2 SNP-window,
      global p = 0.0138 for 3 SNP-window) associations between the 3' genomic interval
      of the gene and schizophrenia. MAP6 transcripts are expressed as two isoforms. A
      postmortem brain expression study showed up-regulation of mRNA isoform 2 in the
      prefrontal cortex (Brodmann's area 46) of patients with schizophrenia. These data
      suggest that the contribution of MAP6 to the processes that lead to schizophrenia
      should be further investigated.

PMID- 16624527
TI  - Case report: intestinal atonia as an unusual symptom of malignant catatonia
      responsive to electroconvulsive therapy.

PMID- 16624528
TI  - Reduced size of the pre-supplementary motor cortex and impaired motor sequence
      learning in first-episode schizophrenia.
AB  - Increasing evidence suggests that schizophrenia is associated with various
      morphological and functional abnormalities of the frontal cortex. So far research
      has concentrated on the dorsolateral and orbitofrontal cortex. Behavioral
      evidence suggests however that regions responsible for higher motor control are
      compromised in schizophrenia as well. The current study assessed volumes of the
      anterior supplementary motor area (pre-SMA) and implicit motor sequence learning
      in 15 subjects with first-episode schizophrenia and 15 healthy matched controls.
      Pre-SMA volumes were assessed by three-dimensional structural magnetic resonance
      imaging (3D-MRI) and manual parcellation according to an established protocol.
      Implicit motor sequence learning was assessed using the Serial Reaction-Time Task
      (SRTT). Compared with control subjects, schizophrenia subjects had significantly
      smaller volumes of the left pre-SMA (16%). Subjects with schizophrenia were
      severely impaired on sequence-specific implicit motor learning. Size of the left
      pre-SMA of schizophrenia subjects was significantly related to impaired implicit
      learning. We conclude that subjects with first-episode schizophrenia have a
      morphological abnormality of the left pre-SMA that might predispose them to
      develop disturbances of higher motor control during acute episodes of psychosis.
      These structural and behavioral abnormalities might be conceptualized within a
      broader model that views schizophrenia as a disorder of disturbed coordination of
      thought and action.

PMID- 16624529
TI  - Neurocognitive and social cognitive correlates of formal thought disorder in
      schizophrenia patients.
AB  - The neurocognitive and social cognitive correlates of two types of formal thought
      disorder (i.e., bizarre-idiosyncratic and concrete thinking) were examined in 47
      stable outpatients with schizophrenia. Both types of thinking disturbance were
      related to impairments in verbal learning, intrusions in verbal memory, immediate
      auditory memory, sustained attention, and social schema knowledge.
      Distractibility during an immediate memory task was associated with more frequent
      bizarre verbalizations but not concreteness. Impaired verbal learning rate and
      intrusions in verbal memory independently contributed to the prediction of
      bizarre responses, whereas intrusions in verbal memory and impaired immediate
      memory independently contributed to concrete thinking. This pattern of findings
      is consistent with the view that neurocognitive and, possibly, social cognitive
      deficits underlie these two aspects of formal thinking disturbance in
      schizophrenia.

PMID- 16624530
TI  - Neuronavigated transcranial magnetic stimulation and auditory hallucinations in a
      schizophrenic patient: monitoring of neurobiological effects.

PMID- 16624531
TI  - Three dimensions of clinical symptoms in elderly patients with schizophrenia:
      prediction of six-year cognitive and functional status.
AB  - BACKGROUND: A three-syndrome categorization of schizophrenia has been recently
      proposed [Arndt, S., Alliger R.J., Andreasen, N.C., 1991. The distinction of
      positive and negative symptoms: the failure of a two-dimensional model. Br. J.
      Psychiatry 158, 317-322; Miller, D.D., Arndt, S., Andreasen, N.C., 1993. Alogia,
      attentional impairment, and inappropriate affect: their status in the dimensions
      of schizophrenia. Comp. Psychiatry 34, 221-226; Gur, R.E., Mozley, D., Resnick,
      S.M., Levick, S., Erwin, R., Saykin, A.J., Gur, R.C., 1991. Relations among
      clinical scales in schizophrenia. Am. J. Psychiatry 148, 472-478. Brown, K.W.,
      White, T., 1992. Syndromes of chronic schizophrenia and some clinical correlates.
      Br. J. Psychiatry 161, pp. 317-322]. METHODS: Chronic, elderly, schizophrenia
      patients with deficit (N = 111), nondeficit with High reality distortion/Low
      conceptual disorganization (nondeficit-delusional) (N = 40) and nondeficit with
      Low reality distortion/High conceptual disorganization (nondeficit-disorganized)
      (N = 56) were followed-up for 6 years. Assessment included the Positive and
      Negative Syndrome Scale (PANSS), the Mini-mental Status Examination (MMSE) and
      the Alzheimer's Disease Assessment-Late Stage Cognitive and Non-Cognitive
      Subscale (ADAS-L Cog and ADAS-L Self care). RESULTS: At initial assessment, MMSE
      scores were significantly lower, while the ADAS-L Cog and Negative symptoms were
      significantly higher in the deficit and nondeficit-disorganized groups compared
      with the nondeficit-delusional group (all p values <0.05). Positive symptoms were
      significantly lower in the deficit group than in both nondeficit syndrome groups
      (p < 0.05). On the ADAS-L Self Care scale the nondeficit-delusional group was the
      most impaired while the nondeficit-disorganized was the least impaired. There was
      a significant decline over time in MMSE scores in the deficit and the nondeficit
      delusional groups (p < 0.01), but no change in the nondeficit-disorganized group.
      ADAS-L Cog and ADAS-L Self Care functions worsened over time in all three groups
      (p < 0.0001). Severity of negative symptoms was stable over time in deficit
      patients and in nondeficit-disorganized patients but worsened in nondeficit
      delusional patients (p < 0.001). There was also a significant worsening of
      positive symptoms over time in deficit patients (p = 0.04). CONCLUSION: Deficit,
      nondeficit-delusional and nondeficit-disorganized patients with schizophrenia may
      represent distinct subgroups discriminated by different courses in negative and
      positive symptoms and cognitive status.

PMID- 16624532
TI  - Protein expression profiling of postmortem brain in schizophrenia.
AB  - Surface enhanced laser desorption/ionization time of flight mass spectrometry
      (SELDI-TOF-MS) enables the sensitive, high-throughput protein profiling of
      complex biological mixtures. In combination with bioinformatics, this technology
      has the potential to identify combinations of spectral peaks that can
      differentiate individuals with a particular disease from normal controls. SELDI
      TOF-MS was used to screen postmortem tissue derived from the dorsolateral
      prefrontal cortex of individuals with schizophrenia (n = 34) and matched controls
      (n = 35), obtained from the Stanley Foundation Neuropathology Consortium. Tissue
      samples were homogenized in urea buffer, applied to four different chip arrays
      which possess different chromatographic surfaces, and analyzed using the
      Ciphergen ProteinChip Biomarkers System (Model PBS II). Protein expression
      profiles of the schizophrenia and control groups were compared and analyzed using
      the Ciphergen Express (CE) and Biomarker Patterns Software (BPS) package. We
      detected several protein peaks whose intensities differed between the
      schizophrenia and control groups to a highly significant degree. A combination of
      these peaks was capable of distinguishing between schizophrenia and controls with
      a sensitivity and specificity of about 70%. The classification model that
      distinguished schizophrenia from controls was complex, suggesting that the
      biochemical abnormalities underlying schizophrenia are heterogeneous. Our results
      suggest that SELDI-TOF-MS has the potential for distinguishing individuals with
      schizophrenia from normal controls and may eventually lead to a better
      understanding of the classification, diagnosis and pathogenesis of this disorder.

PMID- 16624533
TI  - Pharmacokinetic and pharmacodynamic behaviour of antitubercular drugs
      encapsulated in alginate nanoparticles at two doses.
AB  - This study was designed to evaluate the pharmacokinetics and tissue distribution
      of free and alginate-encapsulated antitubercular drugs in mice at different
      doses. Alginate nanoparticles encapsulating isoniazid (INH), rifampicin (RIF),
      pyrazinamide (PZA) and ethambutol (EMB) were prepared by controlled cation
      induced gelification of alginate. The formulation was orally administered to mice
      at two dose levels (D1 and D2). A comparison was made in mice receiving free
      drugs at equivalent doses. Drugs were analysed by high performance liquid
      chromatography (HPLC). The average size of alginate nanoparticles was found to be
      235.5+/-0.0 nm with a polydispersity index of 0.44; drug encapsulation was 70-90%
      for INH and PZA, 80-90% for RIF and 88-95% for EMB. In the free drug groups,
      plasma levels of RIF and INH were higher and PZA and EMB levels were lower in the
      D1 group (per body surface area of mice) compared with the D2 group (recommended
      human dose). The plasma drug levels of all drugs were higher in the D1
      encapsulated group compared with D2, resulting in higher values of area under the
      plasma drug concentration-time curve (AUC(0-infinity)). The relative
      bioavailabilities of all drugs encapsulated in alginate nanoparticles were
      significantly higher compared with free drugs. Drug levels were maintained at or
      above the minimum inhibitory concentration (MIC(90)) until Day 15 in organs after
      administration of encapsulated drugs, whilst free drugs stayed at or above the
      MIC(90) up to Day 1 only irrespective of dose. The levels of drugs in various
      organs remained above the MIC at both doses for equal periods, demonstrating
      their equiefficiency. Alginate nanoparticles hold great potential in reducing
      dosing frequency of antitubercular drugs.

PMID- 16624534
TI  - GABA(A) receptors of hippocampal CA1 regions are involved in the acquisition and
      expression of morphine-induced place preference.
AB  - In the present study, the effects of bilateral intra-hippocampal CA1 (intra-CA1)
      injections of GABA(A) receptor agonist and/or antagonist on the acquisition and
      expression of morphine-induced place preference in male Wistar rats have been
      investigated. The conditioning treatments with subcutaneous (s.c.) injections of
      different doses of morphine (0.5-7.5 mg/kg) induced a conditioned place
      preference (CPP) for the drug-associated place in a dose-dependent manner. Intra
      CA1 administration of the GABA(A) receptor agonist, muscimol (0.25, 0.5 and 1
      microg/rat) significantly inhibited the morphine (5 mg/kg, s.c.)-induced CPP.
      Intra-CA1 injections of different doses of the GABA(A) receptor antagonist,
      bicuculline (0.25, 0.5 and 1 microg/rat), in combination with an ineffective dose
      of morphine (0.5 mg/kg, s.c.) elicited a significant CPP. However, muscimol or
      bicuculline by themselves did not elicit any effect on place conditioning.
      Furthermore, the muscimol-induced inhibition of morphine response was reversed by
      bicuculline (1 microg/rat, intra-CA1) administration. On the other hand, the
      bilateral intra-CA1 injections of muscimol (0.25, 0.5 and 1 microg/rat) or
      bicuculline (0.5, 1 and 2 microg/rat) significantly decreased the expression of
      morphine-induced CPP. Intra-CA1 administration of different doses of muscimol or
      bicuculline had no effect on locomotor activity in the testing phase. Our data
      indicated that the GABA(A) receptors of the hippocampal CA1 regions may play an
      important role in the acquisition and expression of morphine-induced place
      preference.

PMID- 16624535
TI  - Galanin enhances and a galanin antagonist attenuates depression-like behaviour in
      the rat.
AB  - The effect of intracerebroventricular infusion of galanin and/or the galanin
      antagonist M35 was studied in the forced swim test. Animals were pre-exposed to
      water for 15 min 24 h prior to test. Immobility and climbing were assessed during
      the second, 5 min exposure to water. Rats receiving a single infusion of galanin
      (3 nmol) displayed a significant increase of immobility. This effect was blocked
      by co-administration of M35 (1 nmol). M35 alone (1 nmol) produced a significant
      decrease of immobility. The results further support the hypothesis that galanin
      may play a role in mood disorders, and that galanin antagonists may represent new
      candidates for antidepressant treatment.

PMID- 16624536
TI  - Innate immunity in amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition in
      which motor neurons are selectively targeted. Although the underlying cause
      remains unclear, evidence suggests a role for innate immunity in disease
      pathogenesis. Neuroinflammation in areas of motor neuron loss is evident in
      presymptomatic mouse models of ALS and in human patients. Efforts aimed at
      attenuating the inflammatory response in ALS animal models have delayed symptom
      onset and extended survival. Seemingly conversely, attempts to sensitize cells of
      the innate immune system and modulate their phenotype have also shown efficacy.
      Effectors of innate immunity in the CNS appear to have ambivalent potential to
      promote either repair or injury. Because ALS is a syndromic disease in which
      glutamate excitotoxicity, altered cytoskeletal protein metabolism, oxidative
      injury, mitochondrial dysfunction and neuroinflammation all contribute to motor
      neuron degeneration, targeting inflammation via modulation of microglial function
      therefore holds significant potential as one aspect of therapeutic intervention
      and could provide insight into the exclusive vulnerability of motor neurons.

PMID- 16624537
TI  - Comparison of protective effects of aspirin, D-penicillamine and vitamin E
      against high glucose-mediated toxicity in cultured endothelial cells.
AB  - This study compared the protective effects of three different anti-glycation
      compounds, aspirin, D-penicillamine and vitamin E, against high glucose and
      advanced glycation endproduct (AGE) mediated toxicity in cultured bovine aortic
      endothelial cells using two approaches. Their proliferation was assessed in
      culture in different concentrations of glucose (5.5-100 mmol/l) with and without
      these inhibitors. A monolayer of cultured endothelial cells was wounded and
      recovery at the wound site was measured following exposure to different
      concentrations of glucose with and without inhibitors. The ability of these
      compounds to protect cultured endothelial cells following exposure to bovine
      serum albumin-derived advanced glycation endproducts (BSA-AGE) was also studied.
      Addition of glucose to cultured endothelial cells inhibited their proliferation
      in a dose dependent manner. All three compounds protected against the anti
      proliferative effects of high glucose, with vitamin E being the most effective.
      The migration of cultured endothelial cells following wounding was inhibited by
      increasing concentrations of glucose but was maintained in the presence of all
      three anti-glycation compounds with vitamin E, again giving the greatest
      protection. Vitamin E was also the most effective at protecting against the anti
      proliferative effects of BSA-AGE. D-penicillamine was not as effective as vitamin
      E whereas aspirin offered no significant protection against AGE-induced cellular
      toxicity. Our studies suggest that compounds, such as vitamin E, with combined
      antiglycation and antioxidant properties offer maximum therapeutic potential in
      protection against high glucose and AGE-mediated cellular toxicity.

PMID- 16624538
TI  - Homeotic transformations of the axial skeleton of YY1 mutant mice and genetic
      interaction with the Polycomb group gene Ring1/Ring1A.
AB  - Polycomb group (PcG) proteins participate in the maintenance of transcriptionally
      repressed state of genes relevant to cell differentiation. Here, we show anterior
      homeotic transformations of the axial skeleton of YY1(+/-) mice. We find that the
      penetrance of some of these alterations was reduced in mice that are deficient in
      the class II PcG gene Ring1/Ring1A, indicating a genetic interaction between
      those two genes. Further support for this interaction is an abnormal anterior eye
      formation in Ring1-deficient mice, which is enhanced in compound YY1(+/-)Ring1(-/
      ) mice. In addition, YY1 forms complexes with Ring1 and other class II PcG
      proteins such as Rnf2 and Bmi1 in GST pull down experiments in transfected cells.
      These findings provide evidence for a PcG function for YY1 in vertebrates.

PMID- 16624539
TI  - Impact of bronchiectasis on right and left ventricular functions.
AB  - Diffuse systemic-pulmonary anastomoses and chronic hypoxemia may result in
      increase in ventricular work in bronchiectasis. We aimed to assess right
      ventricular (RV) and left ventricular (LV) functions in patients with
      bronchiectasis by using tissue Doppler-derived myocardial performance index
      (MPI), which is a novel and more sensitive parameter than conventional
      ventricular function parameters. To assess the possibility of RV and LV
      dysfunctions occurring in bronchiectasis, we studied 25 patients with
      bronchiectasis, and compared them with 22 age- and gender-matched control
      subjects. MPI, which is a combined index of both systolic and diastolic
      ventricular function, was calculated for both ventricles. RV and LV MPIs were
      also significantly different in patients and the controls. RV MPI was associated
      with the number of involved lobe, arterial blood oxygen pressure, and
      acceleration time/ejection time of pulmonary flow. LV MPI was not related to any
      clinical parameter, but it was correlated only with RV MPI. Ventricular functions
      are impaired in bronchiectasis. The impairment of RV function is related to
      involved lung lobe number, arterial oxygen pressure, and acceleration
      time/ejection time of pulmonary flow. LV dysfunction was correlated only with RV
      function.

PMID- 16624540
TI  - Characterization of shredded television scrap and implications for materials
      recovery.
AB  - Characterization of TV scrap was carried out by using a variety of methods, such
      as chemical analysis, particle size and shape analysis, liberation degree
      analysis, thermogravimetric analysis, sink-float test, and IR spectrometry. A
      comparison of TV scrap, personal computer scrap, and printed circuit board scrap
      shows that the content of non-ferrous metals and precious metals in TV scrap is
      much lower than that in personal computer scrap or printed circuit board scrap.
      It is expected that recycling of TV scrap will not be cost-effective by utilizing
      conventional manual disassembly. The result of particle shape analysis indicates
      that the non-ferrous metal particles in TV scrap formed as a variety of shapes;
      it is much more heterogeneous than that of plastics and printed circuit boards.
      Furthermore, the separability of TV scrap using density-based techniques was
      evaluated by the sink-float test. The result demonstrates that a high recovery of
      copper could be obtained by using an effective gravity separation process.
      Identification of plastics shows that the major plastic in TV scrap is high
      impact polystyrene. Gravity separation of plastics may encounter some challenges
      in separation of plastics from TV scrap because of specific density variations.

PMID- 16624541
TI  - Methane yield in source-sorted organic fraction of municipal solid waste.
AB  - Treating the source-separated organic fraction of municipal solid waste (SS
      OFMSW) by anaerobic digestion is considered by many municipalities in Europe as
      an environmentally friendly means of treating organic waste and simultaneously
      producing methane gas. Methane yield can be used as a parameter for evaluation of
      the many different systems that exist for sorting and pre-treating waste. Methane
      yield from the thermophilic pilot scale digestion of 17 types of domestically SS
      OFMSW originating from seven full-scale sorting systems was found. The samples
      were collected during 1 year using worked-out procedures tested statistically to
      ensure representative samples. Each waste type was identified by its origin and
      by pre-sorting, collection and pre-treatment methods. In addition to the pilot
      scale digestion, all samples were examined by chemical analyses and methane
      potential measurements. A VS-degradation rate of around 80% and a methane yield
      of 300-400Nm(3) CH(4)/ton VS(in) were achieved with a retention time of 15 days,
      corresponding to approximately 70% of the methane potential. The different waste
      samples gave minor variation in chemical composition and thus also in methane
      yield and methane potential. This indicates that sorting and collection systems
      in the present study do not significantly affect the amount of methane produced
      per VS treated.

PMID- 16624542
TI  - Leaching behavior of polychlorinated dibenzo-p-dioxins and furans from the fly
      ash and bottom ash of a municipal solid waste incinerator.
AB  - The leaching behavior of dioxins from landfill containing bottom ash and fly ash
      from municipal solid waste incineration has been investigated by leaching tests
      with pure water, non-ionic surfactant solutions, ethanol solutions, or acetic
      acid solutions as elution solvents for a large-scale cylindrical column packed
      with ash. Larger amounts of dioxins were eluted from both bottom ash and fly ash
      with ethanol solution and acetic acid solution than with pure water. Large
      quantities of dioxins were leached from fly ash but not bottom ash by non-ionic
      surfactant solutions. The patterns of distribution of the dioxin congeners in the
      leachates were very similar to those in the bottom ash or fly ash from which they
      were derived.

PMID- 16624543
TI  - The disposal of radioactive ferric floc.
AB  - An iron hydroxide floc is used as treatment for adsorbing low amounts of
      actinides during nuclear fuel re-processing. This waste is cemented only after
      pre-treatment with Ca(OH)(2). Characterisation of all simulant material has been
      undertaken using XRD, TGA and SEM/EDS. The floc is a moderately alkaline
      colloidal slurry containing approximately 15wt% solids, with the main particulate
      being an amorphous hydrated iron oxide. The main phase formed during pre
      treatment appears to be an X-ray amorphous hydrated calcium-ferrate phase.
      Embedded within this are small amounts of crystalline Ca(OH)(2), calcite,
      Fe(6)(OH)(12)(CO(3)), Ca(6)Fe(2)(SO(4))(3)(OH)(12).26H(2)O and Ca(3)B(2)O(6), and
      can form depending on concentrations of Ca(OH)(2) and time. Apart from Ca(OH)(2)
      and calcite, none of the crystalline phases detected during pre-treatment are
      detected when the floc is encapsulated in an OPC/PFA composite cement hydrated
      for 90 days. The main crystalline phase detected in the hardened wasteform is a
      solid solution hydrogarnet, Ca(3)AlFe(SiO(4))(OH)(8), known as C(3)(A,F)SH(4) in
      cement chemistry nomenclature.

PMID- 16624544
TI  - The use of 'exotic' framework structures in waste management.
AB  - The use of porous framework materials in waste management applications has the
      potential to be a powerful tool in toxic metal remediation. The properties that
      these materials possess, including high surface area and ion-exchange capacity,
      are theoretically valuable. Furthermore, the flexibility of many of these
      frameworks allows the potential for immobilisation of waste materials with the
      framework of the material, in addition to the traditional capture in the pore
      structure. However, for either of these routes to be useful for waste management
      purposes, these structures must also be stable in any proposed storage media.
      This study examines the stability of a range of porous materials whose frameworks
      are made out of zinc and arsenic, both considered toxic minesite wastes, when
      exposed to aqueous media. The three frameworks examined (sodalite analogue
      Na(6)(H(2)O)(8)(ZnAsO(4))(6), open framework K(3)Zn(4)O(AsO(4))(3).3.5H(2)O, and
      an ABW type framework NH(4)ZnAsO(4)) all have similar hydrothermal synthetic
      routes and bulk framework compositions, but differ in counter ion used, pore size
      and complexity of structure. The phases were examined before and after storage in
      an aqueous environment, and their crystallinity and leaching were determined. All
      phases prepared were found to be extremely unstable outside their original
      synthetic environment, and very soluble when exposed to water, calling into
      question their practical use in any environment.

PMID- 16624545
TI  - Registration of T-2 mycotoxin with total internal reflection ellipsometry and QCM
      impedance methods.
AB  - A sensitive optical method of total internal reflection ellipsometry (TIRE) in
      conjunction with immune assay approach was exploited for the registration of T-2
      mycotoxin in a wide range of concentrations from 100 microg/ml down to 0.15
      ng/ml. Association constants of 1.4x10(6) and 1.9x10(7)mol(-1)s for poly- and
      monoclonal T-2 antibodies, respectively, were evaluated from TIRE kinetic
      measurements. According to TIRE data fitting, binding of T-2 molecules to
      antibodies (at saturation) has resulted in the increase in adsorbed layer
      thickness of 4-5 nm. The QCM impedance measurements data showed anomalously large
      mass increase and film softening, most likely, due to the binding of large T-2
      aggregates to antibodies.

PMID- 16624546
TI  - Amperometric phenol biosensor based on laponite clay-chitosan nanocomposite
      matrix.
AB  - A novel strategy to fabricate an amperometric biosensor for phenol determination
      based on chitosan/laponite nanocomposite matrix was described. The composite film
      was used to immobilize PPO on the surface of a glassy carbon electrode. Chitosan
      was utilized to improve the analytical performance of the pure clay-modified
      bioelectrode. The biosensor exhibited a series of properties: good affinity to
      its substrate (the apparent Michaelis-Menten constant for the sensor was found to
      be 0.16 mM), high sensitivity (674 mA M(-1)cm(-2) for catechol) and remarkable
      long-term stability in storage (it retains 88% of the original activity after 60
      days). In addition, optimization of the biosensor construction as well as effects
      of experimental variables such as pH, operating potential and temperature on the
      amperometric response of the sensor were discussed.

PMID- 16624547
TI  - Cancer stem cells: opportunities for novel diagnostics and drug discovery.

PMID- 16624548
TI  - Breast cancer stem cells: an overview.
AB  - The theory that cancer may be originated and sustained by a small proportion of
      stem-like, self-renewing cells (termed 'cancer stem cells') has gained support in
      recent years. Breast cancer stem cells have been identified as CD44+CD24- breast
      tumour cells and have recently been isolated and propagated in vitro. It has been
      demonstrated that these cells exclusively retain the ability to form new tumours
      in mouse models and that they display stem/progenitor cell properties. The
      ability to identify breast cancer stem cells in vivo and to propagate them in
      vitro provides the means to compare them with normal cells, in order to
      investigate from which cell they originate, which molecular alterations
      critically affect them, and how they interact with the microenvironment.
      Elucidation of these critical points is essential to develop new therapeutic
      strategies and to improve diagnosis and prognosis for breast cancer patients.

PMID- 16624549
TI  - International neuroblastoma pathology classification adds independent prognostic
      information beyond the prognostic contribution of age.
AB  - Age has been used as a prognostic factor for patients with peripheral
      neuroblastic tumours (pNTs). The latest analysis disclosed a cut-off around 18
      months for the optimal prognostic distinction. The International Neuroblastoma
      Pathology Classification (INPC) distinguishes favourable and unfavourable
      histology based on the age-appropriate evaluation of histologic indicators (grade
      of neuroblastic differentiation, mitosis-karyorrhexis index) in the categories of
      neuroblastoma and ganglioneuroblastoma, nodular. This study showed that age
      tested by using 3 different cut-offs (12, 18, 24 months) was prognostically
      significant. INPC remained prognostically significant regardless of the age group
      to which it was applied. Prognostic effects of age and histologic indicators were
      independently significant, i.e., age had prognostic ability beyond that of
      histologic indicators, and histologic indicators had prognostic ability beyond
      that of age. Due to the fact that INPC incorporated age factor (18, 60 months) in
      the system, it served better than age by itself for prognostic distinction of pNT
      patients.

PMID- 16624550
TI  - A specific RAD51 haplotype increases breast cancer risk in Jewish non-Ashkenazi
      high-risk women.
AB  - While the precise genes involved in determining familial breast cancer risk in
      addition to BRCA1/2 are mostly unknown, one strong candidate is RAD51. Jewish non
      Ashkenazi women at high-risk for breast/ovarian cancer and ethnically matched
      controls were genotyped using four single nucleotide polymorphisms spanning the
      RAD51 genomic region, and the resulting haplotypes were constructed using the
      GERBIL algorithm. A total of 314 individuals were genotyped: 184 non-Ashkenazi
      high-risk women (119 with breast cancer), and 130 unaffected, average-risk
      ethnically matched controls. Using GEBRIL, three frequent haplotypes were
      constructed. One of the haplotypes (TGTA - coined haplotype 3) was present in
      7.3% (19/260 haplotypes) of controls (n=130) and in 16.8% (40/238 haplotypes) of
      high-risk breast cancer patients (n=119, P=0.001). A specific RAD51 haplotype is
      more prevalent among non-Ashkenazi Jewish high-risk women than in average-risk
      population.

PMID- 16624551
TI  - Linking survival of HER2-positive breast carcinoma patients with surgical
      invasiveness.
AB  - The early peak of relapse in patients with breast carcinomas that overexpress
      HER2 oncoprotein and dissemination to the axillary lymph nodes might be related
      to proliferation of micrometastatic lesions induced by EGF family growth factors
      released at the time of surgery. If the levels of these growth factors have an
      impact on relapse, the survival of patients with positive nodes and HER2-positive
      tumours should be dependent on surgery wideness. To test this hypothesis, HER2
      status of primary tumours from patients included in a randomized clinical trial
      addressing conservative quadrantectomy versus radical mastectomy was
      retrospectively analyzed. In HER2-negative patients, independently of node
      infiltration, and in HER2-positive patients without node infiltration, no
      differences in survival according to the type of surgery were observed. In
      patients with positive nodes and HER2-positive tumours the estimation of the time
      dependent log-hazard ratios showed that radical mastectomy significantly
      increased early death rates (P=0.037).

PMID- 16624552
TI  - KIT mutations and dose selection for imatinib in patients with advanced
      gastrointestinal stromal tumours.
AB  - A recent randomized EORTC phase III trial, comparing two doses of imatinib in
      patients with advanced gastrointestinal stromal tumours (GISTs), reported dose
      dependency for progression-free survival. The current analysis of that study
      aimed to assess if tumour mutational status correlates with clinical response to
      imatinib. Pre-treatment samples of GISTs from 377 patients enrolled in phase III
      study were analyzed for mutations of KIT or PDGFRA by combination of D-HPLC and
      direct sequencing of tumour genomic DNA. Mutation types were correlated with
      patients' survival data. The presence of exon 9-activating mutations in KIT was
      the strongest adverse prognostic factor for response to imatinib, increasing the
      relative risk of progression by 171% (P<0.0001) and the relative risk of death by
      190% (P<0.0001) when compared with KIT exon 11 mutants. Similarly, the relative
      risk of progression was increased by 108% (P<0.0001) and the relative risk of
      death by 76% (P=0.028) in patients without detectable KIT or PDGFRA mutations. In
      patients whose tumours expressed an exon 9 KIT oncoprotein, treatment with the
      high-dose regimen resulted in a significantly superior progression-free survival
      (P=0.0013), with a reduction of the relative risk of 61%. We conclude that tumour
      genotype is of major prognostic significance for progression-free survival and
      overall survival in patients treated with imatinib for advanced GISTs. Our
      findings suggest the need for differential treatment of patients with GISTs, with
      KIT exon 9 mutant patients benefiting the most from the 800 mg daily dose of the
      drug.

PMID- 16624553
TI  - Assessing health-related quality of life in palliative care: comparing patient
      and physician assessments.
AB  - It is often difficult to recruit patients for palliative care studies and severe
      attrition must be expected resulting in biased findings. This may be avoided if
      equivalent information could be obtained from sources other than the patients.
      Therefore, we investigated whether physician assessments can be used to evaluate
      the patients' health-related quality of life (HRQOL). Patient and physician
      assessments of the patients' HRQOL were obtained once a week for up to 13 weeks
      using EORTC QLQ-C30 items. The agreement between patients and physicians at first
      contact (N=115) and for the following 13 weeks combined (total N=263) was
      investigated. Significant differences between patient and physician assessments
      were observed for all HRQOL domains assessed. Physicians reported patients to
      have fewer problems/symptoms than patients did for all HRQOL domains except for
      physical and social functioning. The agreement between patients and physicians
      was poor. Using physician assessments may bias findings and cannot be recommended
      as a substitute for patient self-assessment in palliative care.

PMID- 16624555
TI  - Effect of mineral nutrients on cell growth and self-flocculation of Tolypothrix
      tenuis for the production of a biofertilizer.
AB  - The influence of mineral nutrients on the growth and self-flocculation of
      Tolypothrix tenuis was studied. The identification of possible limiting nutrients
      in the culture medium was performed by the biomass elemental composition
      approach. A factorial experimental design was used in order to estimate the
      contribution of macronutrients and micronutrients, as well as their interactions.
      Iron was identified to be limiting in the culture medium. The micronutrients
      influenced mainly cellular growth without effects on self-flocculation.
      Conversely, the self-flocculation capacity of the biomass increased at higher
      concentrations of macronutrients. The optimization of mineral nutrition of T.
      tenuis allowed a 73% increase in the final biomass level and 3.5 times higher
      flocculation rates.

PMID- 16624554
TI  - Radical prostatectomy for locally advanced prostate cancer: results of a
      feasibility study (EORTC 30001).
AB  - The aim of this open, non-randomised, 2-stage feasibility study was to determine
      whether radical prostatectomy (RP) was safe and could provide cure for good
      prognosis patients with clinical T3 prostate cancer, in a multicentre setting.
      Cure was defined as a 3 months post-operative of undetectable serum PSA in
      combination with the presence of pathologically negative margins in the surgical
      specimen. Forty patients were enrolled of whom 38 were eligible. Six patients (5
      pN+ and 1 pNx) did not meet the inclusion criteria and were excluded leaving 32
      evaluable pN0 patients of whom 19 (59.4%, SE=4.26) achieved a complete response
      (CR) and in whom only two serious toxic events (STEs) were observed. The results
      of the first phase of the study passed the toxicity criteria (<3 STE's) but
      failed on the cure rate (>20 CRs). This resulted in discontinuation of the study
      after the first stage. The main reason for failure was the incidence of positive
      margins in the resected specimen. Although the study was stopped after the first
      phase, 28 of the 32 pN0 patients (87.5%) had undetectable serum PSA at 3 months.
      We continue to believe that RP with extensive resection can be beneficial as
      monotherapy for T3aN0M0 prostate cancer.

PMID- 16624556
TI  - Synergic treatment for monosodium glutamate wastewater by Saccharomyces
      cerevisiae and Coriolus versicolor.
AB  - Biodegradation and decolorization of monosodium glutamate wastewater were carried
      out by using an acidophilus yeast strain of Saccharomyces cerevisiae and Coriolus
      versicolor. For the yeast treatment, the highest COD removal and reducing sugar
      removal efficiency were 76.6% and 80.2%, respectively. The color removal was only
      2%. For C. versicolor treatment, the highest COD removal, color removal and
      reducing sugar removal efficiencies were 78.7%, 56.5% and 90.9%, respectively.
      The synergic treatment process, in which the yeast and C. versicolor were
      successively applied,exhibited great advantage over the individual process.

PMID- 16624557
TI  - Utilization of shrimp industry waste in the formulation of tilapia (Oreochromis
      niloticus Linnaeus) feed.
AB  - A rapid expansion of fisheries is demanding an adequate supply of efficient,
      nutritious and inexpensive fish feed, because feed contributes highly to the cost
      of fish production. Shrimp head, a waste product from the shrimp export industry
      qualifies as an economical, abundant and good quality protein source for fish
      feeds. In the present work, shrimp head silage powder, which contained
      approximately 40% protein, was used as a substitute for fish flour. Four feeds,
      in the form of pellets, were prepared by substituting shrimp head silage for fish
      flour at 0%, 33.3%, 66.6% and 100% dietary levels. Other ingredients such as
      corn, soy, bovine blood, cassava and corn cob flours, soy oil, vitamin premix,
      salt, and other components also were used in the formulation. A commercial fish
      feed was used as the control. The proximate composition of these feeds did not
      differ significantly at p>0.05, except for the protein content of the control
      feed, which was about 30.6% versus 35.4-36.9% protein in the other diets. No
      significant differences (p>0.05 level) in weight and length of juveniles fed with
      the different feeds during a period of 60 days were observed. In all cases, an
      excellent correlation (0.9950-0.9996) between weight and length of juveniles was
      observed. No significant difference in growth of juveniles fed on R1, R2, R3, or
      R4, or the control feed, was observed. Similarly, the proximate analyses of the
      flesh of juveniles did not present significant differences (p>0.05). The result
      of the study indicates that the shrimp head silage could replace fish flour as an
      ingredient in tilapia feed with economic advantages and without sacrificing the
      quality of the feed.

PMID- 16624558
TI  - A new case of autosomal dominant myotonia associated with the V1589M missense
      mutation in the muscle sodium channel gene and its phenotypic classification.
AB  - We report a phenotype associated with the Val1589Met substitution in SCN4A gene
      in a French family which would be better classified as paramyotonia congenita.
      The proband was a 48-year-old woman, who described muscle stiffness and
      occasional flaccid weakness, both symptoms being induced by exercise, cold and
      heat. Severe muscle stiffness affected facial, oropharyngeal and limb muscles
      leading to transient paralysis of these muscles. One sister, two nephews and the
      son of the proband had similar symptoms. Molecular analysis of the muscle sodium
      channel gene (SCN4A) by nucleotide sequencing revealed a G-to-A transition of
      cDNA nucleotide at position 4765 predicting a substitution of methionine for
      valine at position 1589. This shows that the Val1589Met mutation in the SCN4 gene
      may cause different phenotypes, either potassium-aggravated myotonia or
      paramyotonia congenita. Familial or individual factors other than the missense
      mutation per se influence the expression of the disease in sodium channel
      disorders.

PMID- 16624559
TI  - How long do patients spend weaning from CPAP in critical care?
AB  - The purpose of this project was to audit clinical practice and to investigate the
      time taken to wean patients using continuous positive airway pressure (CPAP) as a
      method of respiratory support prior to the introduction of a weaning protocol.
      Data was collected over a two-month period and 43 patients were included in the
      audit. Criteria for inclusion were that each patient had previously received
      mechanical ventilation and was subsequently weaned with the aid of CPAP or had
      received CPAP and was weaning from CPAP alone. The average time taken to wean was
      95 hours (3.96 days) and ranged from one to 41 days. There was no correlation
      between the length of weaning time and the patient's APACHE II Score or the
      length of time spent on invasive ventilation prior to weaning on CPAP. However,
      there was a consistency in the time spent on CPAP as a percentage of the total
      weaning time. The audit identified large variations in the process and time taken
      to wean patients from CPAP. This might suggest that CPAP is used in a routine or
      arbitrary manner rather than a selective response to patients' specific needs.

PMID- 16624560
TI  - Generalizability of center of pressure measures of quiet standing.
AB  - Center of pressure (COP) measures are commonly used as indicators of balance and
      postural control. At present, there are no universally accepted standards in
      research investigating fluctuations in the COP with regard to the number of
      trials or the length of a given trial. The purpose of this study was to use the
      tools of Generalizability Theory (G-Theory) to investigate the reliability of COP
      measures of quiet standing and to establish an optimal measurement protocol. G
      Theory provides a tool that allows us to break down the sources of variation, or
      facets, in a measurement procedure and ultimately design a protocol that provides
      optimal reliability. Fifteen participants completed 10 90-s trials with eyes open
      and closed. COP measures of anterior-posterior standard deviation (SD(AP)),
      medial-lateral SD (SD(ML)), average velocity (Vel), and 95% confidence ellipse
      area (Area) were calculated using the first 30, 60, and 90s of each trial. A G
      study and follow-up D-studies were performed to estimate reliability coefficients
      (G-coefficients). The results of the G-Theory analysis suggest that these COP
      measures reached acceptable levels of reliability (G>or=0.70) with at least five
      60s trials.

PMID- 16624561
TI  - Simple automated system for simultaneous production of 11C-labeled tracers by
      solid supported methylation.
AB  - We herein describe a simple setup for the automated simultaneous synthesis of L
      [methyl-11C]methionine and N-[methyl-11C]choline by solid-supported methylation.
      The setup is extremely simple and easy to adapt to other automated systems and
      due to its versatility, the method can be utilized for the production of other
      radiopharmaceuticals requiring a simple [11C]methylation step. Furthermore, it
      can be used for multiple simultaneous synthesis.

PMID- 16624562
TI  - Blood-brain barrier disruption by stromelysin-1 facilitates neutrophil
      infiltration in neuroinflammation.
AB  - Blood-brain barrier (BBB) opening is mediated by matrix metalloproteinases (MMPs)
      in neuroinflammation. We tested the hypothesis that MMP-3 plays a role in BBB
      damage, using MMP-3 knockout (KO) mice and lipopolysaccharide (LPS)-induced
      opening of the BBB. We found less disruption of the BBB after intracerebral LPS
      injection in MMP-3 KO mice than in wild type (P<0.0006). MMP-3 KO mice had less
      MMP-9 than WT mice but similar levels of activation. Moreover, MMP-9 mRNA levels
      were increased to a similar level in both the MMP-3 KO and WT, suggesting both
      endogenous and exogenous sources. Unbiased stereology showed increased neutrophil
      counts in the brains of MMP-3 WT compared to KO mice. Degradation of tight
      junction proteins, claudin-5 and occludin, and the basal lamina protein, laminin
      alpha1, was less affected in the KO than in the WT. Our results provide the first
      in vivo evidence that MMP-3 attacks the basal lamina and tight junction proteins,
      opening the BBB, thereby facilitating neutrophil influx.

PMID- 16624563
TI  - Taurine reverses neurological and neurovascular deficits in Zucker diabetic fatty
      rats.
AB  - Increased oxidative stress is implicated in the pathogenesis of diabetic
      peripheral neuropathy (DPN). However, the efficacy of antioxidant therapy on DPN
      complicating type 2 diabetes remains unexplored. We therefore determined the
      ability of the antioxidant taurine to reverse deficits of hind limb sciatic motor
      and digital sensory nerve conduction velocity (NCV), nerve blood flow (NBF), and
      sensory thresholds in hyperglycemic Zucker diabetic fatty (ZDF) rats.
      Experimental groups comprised lean nondiabetic (ND), ND treated with taurine (ND
      + T), untreated ZDF diabetic (D), and D rats treated with taurine (D + T).
      Compared to ND rats, 23%, 15% and 56% deficits of motor NCV, sensory NCV and NBF,
      respectively as well as thermal and mechanical hyperalgesia were reversed by
      taurine. An 84% deficit of dorsal root ganglion neuron calcitonin gene-related
      peptide in D rats was prevented by taurine. In summary, the antioxidant taurine
      reverses neurological and neurovascular deficits in experimental type 2 diabetes.

PMID- 16624564
TI  - Effects of pyrrolidine dithiocarbamate on beta-amyloid (25-35)-induced
      inflammatory responses and memory deficits in the rat.
AB  - It has been well established that neuroinflammation is involved in Alzheimer
      disease (AD) pathogenesis. Accumulation and aggregation of beta-amyloid (Abeta)
      peptide in the brains of patients with AD result in activation of glial cells
      which, in turn, initiates neuroinflammatory responses that involve reactive
      oxygen intermediates and release of inflammatory cytokines. In this study,
      bilateral intracerebroventricular (i.c.v.) injections of Abeta (25-35) in the rat
      resulted in impairment in learning and spatial memory and increased
      immunoreactive staining of AD-related neuropathological markers (Abeta, APP) and
      inflammatory mediators (OX-6, COX-2) in CA1 and dentate gyrus regions of the
      hippocampus. Pyrrolidine dithiocarbamate (PDTC) given intraperitoneally 30 min
      before Abeta injection and daily for 7 days postsurgery significantly prevented
      Abeta-induced neuropathological and neuroinflammatory responses, as well as the
      learning and spatial memory deficits. The potential of PDTC for reducing
      cognitive and neuropathological deficits may provide preliminary evidence for a
      new approach of AD treatment.

PMID- 16624565
TI  - Enhanced sensitivity of DJ-1-deficient dopaminergic neurons to energy metabolism
      impairment: role of Na+/K+ ATPase.
AB  - DJ-1 gene mutations lead to an inherited form of early-onset parkinsonism. The
      function of DJ-1 is unclear, though a neuroprotective role has been postulated.
      Electrophysiological recordings were made of striatal and dopaminergic nigral
      neurons both of wild-type (WT) and DJ-1-knockout (DJ-1(-/-)) mice. We assessed
      the responses of dopaminergic cells to combined oxygen and glucose deprivation
      (OGD), and to the mitochondrial toxin rotenone. OGD induced a membrane
      hyperpolarization in nigral neurons from WT mice. Similarly, rotenone
      hyperpolarized neurons and then a depolarization occurred. In DJ-1(-/-) mice, the
      OGD-induced hyperpolarization was significantly enhanced. Moreover, rotenone
      caused a shorter hyperpolarization followed by an irreversible depolarization. To
      evaluate the involvement of Na+/K+ ATPase, we tested ouabain, a Na+/K+ ATPase
      inhibitor, on two distinct neuronal subtypes. Compared to WT mice, in
      dopaminergic neurons from DJ-1(-/-) mice, ouabain induced rapid and irreversible
      membrane potential changes. Notably, this effect was observed at concentrations
      that were unable to produce membrane potential shifts on striatal spiny neurons,
      both from WT and DJ-1(-/-) mice. These findings suggest that DJ-1 loss-of
      function enhances vulnerability to energy metabolism alterations, and that nigral
      neurons are particularly sensitive to Na+/K+ ATPase impairment.

PMID- 16624566
TI  - Alterations of white matter connectivity in first episode schizophrenia.
AB  - Cerebral disconnectivity due to white matter alterations in patients with chronic
      schizophrenia assessed by diffusion tensor imaging has been reported previously.
      The aim of this preliminary study is to investigate whether cerebral
      disconnectivity can be detected as early as the first episode of schizophrenia.
      Intervoxel coherence values were compared by voxel-based t test in 12 patients
      with first episode schizophrenia and 12 age- and gender-matched control groups.
      We detected 14 circumscribed significant clusters (P < 0.02), 3 of them with
      higher, and 11 of them with lower IC values for patients with schizophrenia than
      for healthy control groups. We interpret these white matter alterations in
      different regions to be disconnected fiber tracts already present early in
      schizophrenic disease progression.

PMID- 16624567
TI  - Adaquate fixation of plates for stability during mandibular reconstruction.
AB  - PURPOSE: To determine the most appropriate plate fixation for dispersing the
      stress around screws in mandibular reconstruction. MATERIAL AND METHODS: Forty
      eight three-dimensional reconstructed mandibular models with Central (C) or right
      Lateral (L) defects were created and divided into three groups, fixed with: (1)
      two screws on each side, (2) three screws on the left side with the third (middle
      one) located distally, or (3) three screws on the left side with the third
      (middle one) located proximally. A 300N vertical load was applied to the left
      molar region. The maximum stress was calculated using a finite element method and
      statistically evaluated. RESULTS: Stress was concentrated around the screw at the
      distal end of the mandibular halves on the loaded side ('crucial screw'). For the
      C defect, stress concentrated around the 'crucial screw' was greater when there
      were only two screws for fixation (20.55MPa) than when there were three screws
      (16.17MPa; p=0.022). No significant difference was found between the two groups
      with three screws for fixation. For the L defect on the other hand, stress on the
      'crucial screw' was relatively greater when there were three screws for fixation
      (18.9MPa) than when there were only two screws for (12.83MPa; p=0.051). No
      significant difference was found between the two groups with three screws for
      fixation. As for the reconstruction plate, the stresses on the plates were not
      different among the various screw groups for fixation nor among the C and L
      defects. CONCLUSION: This paradoxical result is explained by plate bowing. Thus
      in large defects screw positions should take into consideration the potential for
      plate bowing.

PMID- 16624568
TI  - Stress responsive DEAD-box helicases: a new pathway to engineer plant stress
      tolerance.
AB  - Abiotic stresses including various environmental factors adversely affect plant
      growth and limit agricultural production worldwide. Minimizing these losses is a
      major area of concern for all countries. Therefore, it is desirable to develop
      multi-stress tolerant varieties. Salinity, drought, and cold are among the major
      environmental stresses that greatly influence the growth, development, survival,
      and yield of plants. UV-B radiation of sunlight, which damages the cellular
      genomes, is another growth-retarding factor. Several genes are induced under the
      influence of various abiotic stresses. Among these are DNA repair genes, which
      are induced in response to the DNA damage. Since the stresses affect the cellular
      gene expression machinery, it is possible that molecules involved in nucleic acid
      metabolism including helicases are likely to be affected. The light-driven shifts
      in redox-potential can also initiate the helicase gene expression. Helicases are
      ubiquitous enzymes that catalyse the unwinding of energetically stable duplex DNA
      (DNA helicases) or duplex RNA secondary structures (RNA helicases). Most
      helicases are members of DEAD-box protein superfamily and play essential roles in
      basic cellular processes such as DNA replication, repair, recombination,
      transcription, ribosome biogenesis and translation initiation. Therefore,
      helicases might be playing an important role in regulating plant growth and
      development under stress conditions by regulating some stress-induced pathways.
      There are now few reports on the up-regulation of DEAD-box helicases in response
      to abiotic stresses. Recently, salinity-stress tolerant tobacco plants have
      already been raised by overexpressing a helicase gene, which suggests a new
      pathway to engineer plant stress tolerance [N. Sanan-Mishra, X.H. Pham, S.K.
      Sopory, N. Tuteja, Pea DNA helicase 45 overexpression in tobacco confers high
      salinity tolerance without affecting yield. Proc. Natl. Acad. Sci. USA 102 (2005)
      509-514]. Presently the exact mechanism of helicase-mediated stress tolerance is
      not understood. In this review we have described all the reported stress-induced
      helicases and also discussed the possible mechanisms by which they can provide
      stress tolerance.

PMID- 16624569
TI  - The influence of temperature on photodynamic cell killing in vitro with 5
      aminolevulinic acid.
AB  - Cell survival was investigated after exposing cells in vitro to different
      temperatures before or after photodynamic therapy with 5-aminolevulinic acid. The
      photodynamic process was found to be temperature dependent. Cells exposed for 1h
      to 41 degrees C before light exposure or to 7 degrees C after light exposure
      showed decreased survival. Furthermore, the photobleaching rate of protoporphyrin
      IX in the cells was found to increase with increasing temperature during the
      light exposure. Thus, the photodynamic effect with 5-aminolevulinic acid may be
      enhanced by heating the tumour area before, and by cooling it immediately after
      the treatment.

PMID- 16624570
TI  - Effects of HeNe laser irradiation on experimental paracoccidioidomycotic lesions.
AB  - Paracoccidioidomycosis (PCM) is the most prevalent human mycosis in Latin
      America. The infection is thought to take place firstly in the lungs and then may
      disseminate to other organs and tissues. Treatment by currently available
      antifungals is lengthy, the drugs may have undesirable side effects, and some are
      costly. Occasional resistant strains of Paracoccidioides brasiliensis, the
      causative agent of PCM, have been reported. So, the search for more efficient
      treatments or adjuvant therapies has to be continued. In this work, we evaluated
      the effects of HeNe laser irradiation on cutaneous inflammatory lesions caused by
      the inoculation of 5 x 10(6)/0.1ml yeasts cells into the back footpad of Balb/c
      mice. HeNe irradiation (lambda=632.8nm, 3mW, incident energy of 3J/cm(2)) was
      applied at days 7, 8 and 9 post-infection and histological and
      immunohistochemical analysis were done. Unirradiated animals were used as
      controls. The results showed that laser-treated mice presented reduction of
      footpad edema, faster cutaneous wound healing, confluent granuloma, diffuse- and
      more loosely distributed immunolabeling for TNF-alpha, enhanced labeling of IFN
      gamma and any P. brasiliensis form detected, whereas multiple viable fungi were
      seen in diffuse widespread granulomas obtained from non-treated mice foot-pad.
      Fungi that were harvested from laser-treated animals presented no capability of
      growth in vitro as compared to those obtained from non-treated mice. We conclude
      that HeNe laser irradiation was able to inhibit the progress of inflammatory
      local reaction produced by P. brasiliensis infection and influence local
      cytokines production. We suggest that this treatment modality can be a useful
      coadjuvant tool to be combined with antifungal agents in the treatment of PCM
      ulcerations. The mechanisms involved in laser therapy of PCM lesions need further
      investigation.

PMID- 16624572
TI  - Partial purification of human parathyroid hormone 1-84 as a thioredoxin fusion
      form in recombinant Escherichia coli by thermoosmotic shock.
AB  - A modified purification method, thermoosmotic shock (osmotic shock coupled with
      heat-treatment) for heat-stable proteins, was devised in the purification of Trx
      hPTH (1-84) (human parathyroid hormone coupled with thioredoxin as a fusion
      partner) from E. coli. Thermoosmotic shock can integrate the functions of
      extraction and crude separation of fusion protein Trx-hPTH (1-84). To improve the
      purification efficiency, thermoosmotic shock conditions were optimized and
      achieved as follows: the optimized high osmotic solution containing 20mM Tris-HCl
      buffer (pH 8.0), 1mM EDTA, and 25% sucrose; the low osmotic solution containing
      20mM Tris-HCl buffer (pH 8.0), 1mM EDTA, and the heat-treatment temperature of
      100 degrees C for 10 min. Using this method, the purity of Trx-hPTH (1-84) was up
      to 73% and the yield was up to 72%, respectively. In addition, the two separation
      methods of both thermoosmotic shock and affinity chromatography have been
      compared, indicating that thermoosmotic shock is an economical and feasible way
      for the fusion protein separation. Besides, the thermoosmotic shock method may be
      used for the purification of some proteins of thermal stability without N
      terminal His-tag.

PMID- 16624573
TI  - Native tubulin-folding cofactor E purified from baculovirus-infected Sf9 cells
      dissociates tubulin dimers.
AB  - Tubulin-folding cofactor E (TBCE) is an alpha-tubulin-binding protein involved in
      the formation of the tubulin dimer and in microtubule dynamics, through the
      regulation of tubulin heterodimer dissociation. TBCE has also been implicated in
      two important related human disorders, the Kenny-Caffey and Sanjad-Sakati
      syndromes. The expression of TBCE as a recombinant protein in bacteria results in
      the formation of insoluble inclusion bodies in the absence of denaturing agents.
      Although the active protein can be obtained from mammalian tissues, biochemical
      studies of TBCE present a special challenge. To express and purify native TBCE, a
      recombinant baculovirus expression system was used. Native wild-type TBCE
      purified from Sf9 extracts was sequentially purified chromatographically through
      cation exchange, hydrophobic interaction, and high-resolution gel-filtration
      columns. Mass spectrometric analysis identified 30% of the sequence of human
      TBCE. A stoichiometric excess of purified TBCE dissociated tubulin heterodimers.
      This reaction produced a highly unstable TBCE-alpha-tubulin complex, which formed
      aggregates. To distinguish between the aggregation of tubulin dimers induced by
      TBCE and tubulin dissociation, TBCE and tubulin were incubated with tubulin
      folding cofactor A (TBCA). This cofactor captures the beta-tubulin released from
      the heterodimer with a stoichiometry of 1:1, as previously demonstrated. The beta
      tubulin polypeptide was recovered as TBCA-beta-tubulin complexes, as demonstrated
      by non-denaturing gel electrophoresis and specific antibodies directed against
      beta-tubulin and TBCA.

PMID- 16624571
TI  - Novel beta subunit mutation causes a slow-channel syndrome by enhancing
      activation and decreasing the rate of agonist dissociation.
AB  - We traced the cause of a slow-channel syndrome (SCS) in a patient with
      progressive muscle weakness, repetitive compound muscle action potential and
      prolonged low amplitude synaptic currents to a V --> F substitution in the M1
      domain of the beta subunit (betaV229F) of the muscle acetylcholine receptor
      (AChR). In vitro expression studies in Xenopus oocytes indicated that the novel
      mutation betaV229F expressed normal amounts of AChRs and decreased the ACh EC50
      by 10-fold compared to wild type. Kinetic analysis indicated that the mutation
      displayed prolonged mean open duration and repeated openings during activation.
      Prolonged openings caused by the betaV229F mutation were due to a reduction in
      the channel closing rate and an increase in the effective channel opening rate.
      Repeated openings of the channel during activation were caused by a significant
      reduction in the agonist dissociation constant. In addition, the betaV229F
      mutation produced an increase in calcium permeability. The kinetic and permeation
      studies presented in this work are sufficient to explain the consequences of the
      betaV229F mutation on the miniature endplate currents and thus are direct
      evidence that the betaV229F mutation is responsible for compromising the safety
      margin of neuromuscular transmission in the patient.

PMID- 16624574
TI  - Expression and purification of two lipases from Yarrowia lipolytica AS 2.1216.
AB  - We isolated two lipase genes LIPY7, LIPY8 from Yarrowia lipolytica CGMCC (China
      general microbiological culture collection center) AS 2.1216. The LIPY7 and LIPY8
      genes encode a 366 and a 371-amino acid protein, respectively. The lipase genes
      with 6 x His tag sequence were cloned into expression vector pPIC9K and
      successfully integrated into a heterologous fungal host Pichia pastoris KM71,
      respectively. The recombinants were induced by methanol to secrete active lipases
      into cultural medium. The recombinant lipases were also purified and
      characterized.

PMID- 16624575
TI  - Recombinant expression and partial characterization of an active soluble histo
      aspartic protease from Plasmodium falciparum.
AB  - Malaria aspartic proteases are attractive drug targets for the treatment of
      malaria, however, recombinant expression of active histo-aspartic proteinase
      (HAP) to facilitate its characterization has proven elusive. The present study
      reports on the first recombinant expression of soluble, active histo-aspartic
      proteinase from Plasmodium falciparum as a thioredoxin fusion protein. A
      truncated form of HAP (77p-451) was fused to thioredoxin in the pET32b(+) vector
      and the fusion protein (Trx-tHAP) was expressed in Escherichia coli Rosetta-gami
      B (DE3)pLysS. The fusion protein was partially purified from the culture medium
      using a combination of anion exchange and Ni(2+) affinity chromatography. Soluble
      tHAP was subsequently purified by enterokinase treatment and removal, followed by
      gel filtration chromatography. Although truncated HAP was incapable of
      autocatalytic activation, enterokinase digestion of partially purified fusion
      protein released the truncated prosegment yielding a mature form of tHAP (mtHAP).
      N-terminal sequencing of mtHAP indicated that enterokinase cleavage took place at
      Lys119-Ser120, four residues upstream of the native cleavage site (Gly123
      Ser124). Initial activity tests showed that mtHAP was capable of hydrolyzing acid
      denatured globin as well as cleavage of the synthetic substrate EDANS-CO-CH(2)
      CH(2)-CO-ALERMFLSFP-Dap(DABCYL)-OH. Inhibition studies showed that the activity
      of mtHAP was completely inhibited by pepstatin A and to a lesser degree, PMSF.
      Using the synthetic substrate, mtHAP showed a pH optimum of 5.2, and Km=3.4
      microM and kcat=1.6 x 10(-3)s(-1). The successful expression of active
      recombinant HAP from E. coli will accelerate the investigation of the structure
      function relationships of HAP and facilitate the development of specific
      inhibitors with antimalarial activities.

PMID- 16624576
TI  - Shoulder joint kinematics during elevation measured by ultrasound-based measuring
      system.
AB  - In order to analyze shoulder joint movements, the authors use a ZEBRIS CMS-HS
      ultrasound-based movement analysis system. In essence, the measurement involves
      the determination of the spatial position of the 16 anatomical points, which are
      specified on the basis of the coordinates of ultrasound-based triplets positioned
      on the upper limb, the scapula, and the thorax; their spatial position is
      measured in the course of motion. Kinematic characteristics of 74 shoulder joints
      of 50 healthy persons were identified during elevation in the plane of the
      scapula. Kinematic characteristics of motion were identified by scapulothoracic,
      glenohumeral, and humeral elevation angles; range of angles; scapulothoracis and
      glenohumeral rhythm; scapulothoracic, glenohumeral, and scapuloglenoid ratios;
      and the relative displacement between the rotation centers of the humerus and the
      scapula. Motion of the humerus and the scapula relative to each other was
      characterized by their rotation as well as the relative displacement between the
      rotation centers of scapula and humerus. The biomechanical model of the shoulder
      joint during elevation can be described by analyzing the results of the
      measurements performed.

PMID- 16624578
TI  - A visual joke fMRI investigation into Theory of Mind and enhanced risk of
      schizophrenia.
AB  - Theory of Mind (ToM) or mentalizing is the ability of individuals to determine
      the intentions and behavior of others. This ability is known to be compromised in
      schizophrenia and has been shown to fluctuate with symptom severity.
      Neuropsychological investigations into relatives of individuals with
      schizophrenia have shown that some relatives also show a deficit in this area of
      social cognition. In order to address this state and trait issue, we investigated
      the performance of high-risk relatives of individuals with schizophrenia to those
      of a matched control group (n = 13) on a blocked design visual joke fMRI
      paradigm. The task involved looking at two sets of cartoon jokes, one set which
      required mentalizing abilities to understand the jokes and another set that did
      not require such abilities. Relatives were divided into two groups based on the
      presence (HR+, n = 12) or absence (HR-, n = 12) of positive symptoms. The task
      provided robust activations across the groups in areas previously associated with
      mentalizing abilities, such as the PFC, precuneus, and temporal lobes.
      Significant between-group activations were observed in the PFC (primarily BA6, 8,
      and 9) with the HR- activating significantly greater than the HR+ in these
      regions. Both a secondary state-specific analysis and a third post hoc analysis
      further investigating state effects showed significant PFC between-group
      differences. This study is the first time relatives of individuals with
      schizophrenia have been imaged using a ToM paradigm, and the results provide
      evidence of both a state and state-mediated trait effect.

PMID- 16624579
TI  - Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion
      data.
AB  - There has been much recent interest in using magnetic resonance diffusion imaging
      to provide information about anatomical connectivity in the brain, by measuring
      the anisotropic diffusion of water in white matter tracts. One of the measures
      most commonly derived from diffusion data is fractional anisotropy (FA), which
      quantifies how strongly directional the local tract structure is. Many imaging
      studies are starting to use FA images in voxelwise statistical analyses, in order
      to localise brain changes related to development, degeneration and disease.
      However, optimal analysis is compromised by the use of standard registration
      algorithms; there has not to date been a satisfactory solution to the question of
      how to align FA images from multiple subjects in a way that allows for valid
      conclusions to be drawn from the subsequent voxelwise analysis. Furthermore, the
      arbitrariness of the choice of spatial smoothing extent has not yet been
      resolved. In this paper, we present a new method that aims to solve these issues
      via (a) carefully tuned non-linear registration, followed by (b) projection onto
      an alignment-invariant tract representation (the "mean FA skeleton"). We refer to
      this new approach as Tract-Based Spatial Statistics (TBSS). TBSS aims to improve
      the sensitivity, objectivity and interpretability of analysis of multi-subject
      diffusion imaging studies. We describe TBSS in detail and present example TBSS
      results from several diffusion imaging studies.

PMID- 16624580
TI  - Effect of task difficulty on the functional anatomy of temporal processing.
AB  - Temporal processing underlies many aspects of human perception, performance and
      cognition. The present study used fMRI to examine the functional neuroanatomy of
      a temporal discrimination task and to address two questions highlighted by
      previous studies: (1) the effect of task difficulty on neuronal activation and
      (2) the involvement of the dorsolateral prefrontal cortex (DLPFC) in timing.
      Twenty healthy subjects were scanned while either judging whether the second in a
      pair of tones was shorter or longer in duration than the standard tone or simply
      responding to the presentation of two identical tones as a control condition. Two
      levels of difficulty were studied. Activation during the less difficult condition
      was observed only in the cerebellum and superior temporal gyrus. As difficulty
      increased, additional activation of the supplementary motor area,
      insula/operculum, DLPFC, thalamus and striatum was observed. These results
      suggest the cerebellum plays a critical role in timing, particularly in gross
      temporal discrimination. These results also suggest that recruitment of frontal
      and striatal regions during timing tasks is load-dependent. Additionally, robust
      activation of the dorsolateral prefrontal cortex under conditions of minimal
      working memory involvement supports the specific involvement of this region in
      temporal processing rather than a more general involvement in working memory.

PMID- 16624581
TI  - Cognitive priming in sung and instrumental music: activation of inferior frontal
      cortex.
AB  - Neural correlates of the processing of musical syntax-like structures have been
      investigated via expectancy violation due to musically unrelated (i.e.,
      unexpected) events in musical contexts. Previous studies reported the implication
      of inferior frontal cortex in musical structure processing. However - due to the
      strong musical manipulations - activations might be explained by sensory deviance
      detection or repetition priming. Our present study investigated neural correlates
      of musical structure processing with subtle musical violations in a musical
      priming paradigm. Instrumental and sung sequences ended on related and less
      related musical targets. The material controlled sensory priming components, and
      differences in target processing required listeners' knowledge on musical
      structures. Participants were scanned with functional Magnetic Resonance Imaging
      (fMRI) while performing speeded phoneme and timbre identification judgments on
      the targets. Behavioral results acquired in the scanner replicated the
      facilitation effect of related over less-related targets. The blood oxygen level
      dependent (BOLD) signal linked to target processing revealed activation of right
      inferior frontal areas (i.e., inferior frontal gyrus, frontal operculum, anterior
      insula) that was stronger for less-related than for related targets, and this was
      independent of the material carrying the musical structures. This outcome points
      to the implication of inferior frontal cortex in the processing of syntactic
      relations also for musical material and to its role in the processing and
      integration of sequential information over time. In addition to inferior frontal
      activation, increased activation was observed in orbital gyrus, temporal areas
      (anterior superior temporal gyrus, posterior superior temporal gyrus and sulcus,
      posterior middle temporal gyrus) and supramarginal gyrus.

PMID- 16624582
TI  - Finger motion sensors for fMRI motor studies.
AB  - The kinematics of motor task performance affect brain activity. However, few
      functional magnetic resonance imaging (fMRI) motor studies have accounted for on
      line kinematics because there are currently few MRI-compatible devices to record
      motor performance. We built a device based on Micro-Electro-Mechanical System
      (MEMS) gyroscopes that measures the angular velocity of one segment of each of
      the 10 fingers while a subject performs a finger motor task during fMRI. Finger
      position, acceleration, and jerk were computed from the angular velocity
      measurements. The signal-to-noise ratio (SNR) of the MEMS sensors (range: 27.10
      34.36 dB) allowed for clear detection of velocity of finger motion during fMRI
      motor task performance, and showed good stability over time. We demonstrate that
      use of the MEMS-based device, while negligibly increasing radiofrequency (RF)
      noise in the scanning environment, did not cause MR image artifacts nor alter
      fMRI statistical activation maps. Further, we show that signal from the MEMS
      sensors was not affected by the high static magnetic field (3 T). Increasing the
      RF power transmitted during fMRI by using a body coil, as compared to a head
      coil, decreased the sensor's SNR from 30.7 to 24.2 dB, though this loss in SNR
      did not interfere with the ability to measure velocity of finger motion. We
      demonstrate the utility of the MEMS-based device in fMRI motor studies through
      two experiments that examined the relationship between finger movement kinematics
      and fMRI activation in the healthy and injured brain. On-line acquisition of
      motor performance during fMRI, through the use of the MEMS-based device, promises
      to allow for a more detailed understanding of the relationship between movement
      kinematics and activation in the healthy and injured brain.

PMID- 16624583
TI  - Dissociable contributions of the mid-ventrolateral frontal cortex and the medial
      temporal lobe system to human memory.
AB  - Although the prefrontal cortex and regions of the medial temporal lobe are
      commonly co-activated in neuroimaging studies, their precise respective
      contributions to human memory remain unclear. In this event-related fMRI study,
      conditions requiring volunteers to simply look at pictures of abstract art were
      compared with conditions in which they were explicitly instructed to remember
      similar stimuli for later recognition. Looking, with no explicit instruction to
      remember, was associated with significant increases in signal intensity in the
      medial temporal lobe in 19 of the 20 volunteers scanned, but not in a region of
      the mid-ventrolateral prefrontal cortex that has previously been implicated in
      memory encoding and retrieval. Behavioral data collected outside the scanner on
      the same task revealed that recognition of these stimuli was, however, above
      chance. When the task instructions were changed to encourage the volunteers to
      remember the stimuli, significant increases in signal intensity were observed
      bilaterally, in the mid-ventrolateral frontal cortex, but there was no
      concomitant increase within the medial temporal lobe region. Moreover, behavioral
      data collected outside the scanner confirmed that recognition of these stimuli
      was significantly improved relative to the 'just look' trials. These results
      suggest that the mid-ventrolateral frontal cortex and the medial temporal lobe
      region make dissociable contributions to human memory that correspond closely to
      'top-down' and 'bottom-up' notions of cognitive control, respectively.

PMID- 16624584
TI  - Maturation of luminance- and motion-defined form perception beyond adolescence: a
      combined ERP and fMRI study.
AB  - Abilities to discriminate forms defined by motion continue to develop throughout
      childhood. To investigate late development of the visual motion system, we
      measured brain activity with event-related EEG potentials (ERPs) and functional
      magnetic resonance imaging (fMRI) in groups of adolescents (15-17 years) and
      adults (20-30 years) during a visual form discrimination task--with forms being
      either defined by motion or luminance contrast. We further explored whether
      possible developmental changes varied with the degree of motion coherence
      reflecting maturation specific to global motion processing. Both the fMRI
      activation patterns and ERP topographies were very similar between adolescents
      and adults, suggesting that the basic visual networks for processing motion and
      form are established by the age of 15-17. The ERP response to luminance- and
      motion-defined forms was dominated by a posterior negativity (N1: 120-270 ms).
      The N1 of the motion contrast was delayed in adolescents, whereas the N1 of the
      static condition did not differ between groups. Since the motion-evoked N1 is
      thought to arise in the middle temporal area MT/V5, our results indicate that
      visual motion processing in MT continues to get faster, becoming still more
      efficient during late development. Neither the ERP nor the fMRI results revealed
      maturation effects specific to motion coherence. This indicates that the specific
      mechanisms to process global dot motion are already mature in adolescence. The
      present findings support the view that static perception matures earlier than
      dynamic perception, and that these visual systems have different developmental
      courses.

PMID- 16624585
TI  - Relationship between antisocial behavior and regional cerebral blood flow in
      frontotemporal dementia.
AB  - OBJECTIVE: To examine the relationship between antisocial behaviors and reduction
      of regional cerebral blood flow (rCBF) in patients with frontotemporal dementia
      (FTD). METHODS: Brain perfusion single photon emission computed tomography
      (SPECT) was performed in 22 patients with FTD and 76 age-matched healthy
      volunteers. The statistical analysis was conducted using the SPM99 software. The
      antisocial behavioral symptoms were assessed independently by three geriatric
      psychiatrists, who had not been given the information of the SPECT images.
      RESULTS: Compared with normal controls, FTD patients showed significant reduction
      of rCBF in the widespread frontal cortical areas. The correlation analysis showed
      that antisocial behavioral symptoms are associated with reduction of rCBF in the
      orbitofrontal cortex. CONCLUSION: The functional decline of orbitofrontal cortex
      is related to antisocial behavioral symptoms in patients with FTD.

PMID- 16624586
TI  - Unified framework for anisotropic interpolation and smoothing of diffusion tensor
      images.
AB  - To enhance the performance of diffusion tensor imaging (DTI)-based fiber
      tractography, this study proposes a unified framework for anisotropic
      interpolation and smoothing of DTI data. The critical component of this framework
      is an anisotropic sigmoid interpolation kernel which is adaptively modulated by
      the local image intensity gradient profile. The adaptive modulation of the
      sigmoid kernel permits image smoothing in homogeneous regions and meanwhile
      guarantees preservation of structural boundaries. The unified scheme thus allows
      piece-wise smooth, continuous and boundary preservation interpolation of DTI
      data, so that smooth fiber tracts can be tracked in a continuous manner and
      confined within the boundaries of the targeted structure. The new interpolation
      method is compared with conventional interpolation methods on the basis of fiber
      tracking from synthetic and in vivo DTI data, which demonstrates the
      effectiveness of this unified framework.

PMID- 16624587
TI  - Functional imaging of the intraparietal cortex during saccades to visual and
      memorized targets.
AB  - The representation of perceived space and intended actions in the primate
      parietal cortex has been the subject of considerable debate. To address this
      issue, we used the quantitative 14C-deoxyglucose method to obtain maps of the
      activity pattern in the intraparietal cortex of rhesus monkeys executing saccades
      to visual and memorized targets. The principal effect induced by memory-guided
      saccades was found more caudally in the deepest part of the middle third of the
      lateral bank (within area LIPv) whereas that induced by visually guided saccades
      extended more rostrally and superficially in the anterior third of the bank
      (within area LIPd). The memory-saccade-related and the visual-saccade-related
      regions of activation overlapped only within area LIPv. Besides saccade
      execution, maximal activity in area LIPd required a visual stimulus. The region
      activated by visual fixation was located at the border of LIPv and LIPd,
      extending mainly within area LIPd, and occupying about one third of the neural
      space of the region activated for visual-saccades. We suggest that the lateral
      intraparietal cortex represents visual and motor space in segregated, albeit
      partially overlapping, regions.

PMID- 16624588
TI  - Strategies for improving the detection of fMRI activation in trigeminal pathways
      with cardiac gating.
AB  - Functional magnetic resonance imaging (fMRI) has become a powerful tool for
      studying the normal and diseased human brain. The application of fMRI in
      detecting neuronal signals in the trigeminal system, however, has been hindered
      by low detection sensitivity due to activation artifacts caused by cardiac pulse
      induced brain and brainstem movement. A variety of cardiac gating techniques have
      been proposed to overcome this issue, typically by phase locking the sampling to
      a particular time point during each cardiac cycle. We sought to compare different
      cardiac gating strategies for trigeminal system fMRI. In the present study, we
      used tactile stimuli to elicit brainstem and thalamus activation and compared the
      fMRI results obtained without cardiac gating and with three different cardiac
      gating strategies: single-echo with TR of 3 or 9 heartbeats (HBs) and dual-echo
      T2*-mapping EPI (TR = 2 HBs, TE = 21/55 ms). The dual-echo T2* mapping and the
      single-echo with TR of 2 and 3 HBs cardiac-gated fMRI techniques both increased
      detection rate of fMRI activation in brainstem. Activation in the brainstem and
      the thalamus was best detected by cardiac-gated dual-echo EPI.

PMID- 16624589
TI  - EEG-fMRI of idiopathic and secondarily generalized epilepsies.
AB  - We used simultaneous EEG and functional MRI (EEG-fMRI) to study generalized spike
      wave activity (GSW) in idiopathic and secondary generalized epilepsy (SGE).
      Recent studies have demonstrated thalamic and cortical fMRI signal changes in
      association with GSW in idiopathic generalized epilepsy (IGE). We report on a
      large cohort of patients that included both IGE and SGE, and give a functional
      interpretation of our findings. Forty-six patients with GSW were studied with EEG
      fMRI; 30 with IGE and 16 with SGE. GSW-related BOLD signal changes were seen in
      25 of 36 individual patients who had GSW during EEG-fMRI. This was seen in
      thalamus (60%) and symmetrically in frontal cortex (92%), parietal cortex (76%),
      and posterior cingulate cortex/precuneus (80%). Thalamic BOLD changes were
      predominantly positive and cortical changes predominantly negative. Group
      analysis showed a negative BOLD response in the cortex in the IGE group and to a
      lesser extent a positive response in thalamus. Thalamic activation was consistent
      with its known role in GSW, and its detection in individual cases with EEG-fMRI
      may in part be related to the number and duration of GSW epochs recorded. The
      spatial distribution of the cortical fMRI response to GSW in both IGE and SGE
      involved areas of association cortex that are most active during conscious rest.
      Reduction of activity in these regions during GSW is consistent with the clinical
      manifestation of absence seizures.

PMID- 16624590
TI  - Mapping anatomical correlations across cerebral cortex (MACACC) using cortical
      thickness from MRI.
AB  - We introduce MACACC-Mapping Anatomical Correlations Across Cerebral Cortex-to
      study correlated changes within and across different cortical networks. The
      principal topic of investigation is whether the thickness of one area of the
      cortex changes in a statistically correlated fashion with changes in thickness of
      other cortical regions. We further extend these methods by introducing techniques
      to test whether different population groupings exhibit significantly varying
      MACACC patterns. The methods are described in detail and applied to a normal
      childhood development population (n = 292), and show that association cortices
      have the highest correlation strengths. Taking Brodmann Area (BA) 44 as a seed
      region revealed MACACC patterns strikingly similar to tractography maps obtained
      from diffusion tensor imaging. Furthermore, the MACACC map of BA 44 changed with
      age, older subjects featuring tighter correlations with BA 44 in the anterior
      portions of the superior temporal gyri. Lastly, IQ-dependent MACACC differences
      were investigated, revealing steeper correlations between BA 44 and multiple
      frontal and parietal regions for the higher IQ group, most significantly (t =
      4.0) in the anterior cingulate.

PMID- 16624591
TI  - Dispersal and vicariance: the complex evolutionary history of boid snakes.
AB  - Since the early 1970s, boine snakes (Boidae: Boinae) have served as a prime
      example of a group whose current distribution was shaped by vicariant events
      associated with the fragmentation of the supercontinent Gondwana. Early
      phylogenetic treatments of this group, and what were thought to be closely
      related groups (Erycinae and Pythoninae) based on morphological features,
      produced a relatively stable view of relationships that has strongly influenced
      subsequent molecular-based work. We examined 4307 base pairs (bp) of nucleotide
      sequence data obtained from five nuclear loci (c-mos, NT3, BDNF, RAG1, and ODC)
      and one mitochondrial locus (cyt b) for all genera of erycines and boines, plus
      representatives of other groups, including those previously thought to be closely
      allied with boines (Ungaliophiidae, Loxocemidae, Xenopeltidae, and Pythoninae).
      Our results suggest that the Boidae is not monophyletic, and its current division
      into three subfamilies (Erycinae, Boinae, and Pythoninae) does not accurately
      reflect evolutionary history. We find that the evolutionary relationships are
      better reflected by current geographic distributions and tectonic history than by
      the morphological characters that have long served as the foundation of boid
      phylogeny. Divergence time estimates suggest that this strong congruence between
      geography and phylogeny is the result of several vicariant and dispersal events
      in the Late Cretaceous and Paleocene associated with the fragmentation of the
      Gondwanan supercontinent. Our results demonstrate the importance of both
      vicariance and dispersal in shaping the global distributions of terrestrial
      organisms.

PMID- 16624592
TI  - The mahogany family "out-of-Africa": divergence time estimation, global
      biogeographic patterns inferred from plastid rbcL DNA sequences, extant, and
      fossil distribution of diversity.
AB  - With information on fossils and extant distribution of diversity/endemism in the
      mahogany family, we perform a global biogeographic study of Meliaceae using
      plastid rbcL data for all subfamilies, tribes and nearly all genera. Our study
      indicates that: (1) Meliaceae are of western Gondwanan origin; (2) dispersal
      played an important role for the current distribution of mahogany biota; and (3)
      the direction of dispersal was most likely an "out-of-Africa" scenario with
      important dispersal routes across Eurasia and between Eurasia and North America
      provided by Beringia and the North Atlantic land bridge and North America and
      South America via island chains and/or direct land connections. Populations in
      North America, Europe, and East Asia were presumably eliminated as tropical
      climates disappeared from these areas during the Miocene. Extensive Meliaceae
      fossil findings confirm that the entry of megathermal (frost-intolerant)
      angiosperms into southern continents from Oligocene to Pliocene must be
      considered as an important means of establishing pantropical distribution
      patterns.

PMID- 16624593
TI  - Molecular phylogenetic relationship of snow finch complex (genera Montifringilla,
      Pyrgilauda, and Onychostruthus) from the Tibetan plateau.
AB  - The snow finch complex (Montifringilla, Pyrgilauda, and Onychostruthus) has its
      center of distribution on the Tibetan plateau, with six out of seven species in
      the genera occurring there. Phylogenetic relationships among these six species of
      three genera have been studied based on DNA sequence data obtained from the
      mitochondrial cytochrome b gene and the nuclear myoglobin gene. The results
      support monophyly of the snow finch complex group and three major evolutionary
      lineages are recognized. The first clade consists of ruficollis, blanfordi, and
      davidiana. These three taxa are sometimes placed in their own genus, Pyrgilauda,
      and the DNA data supports this. The three taxa nivalis, henrici, and adamsi have
      traditionally been placed in the genus Montifringilla, and they group together
      strongly in the present analysis. The results further suggest that nivalis and
      adamsi are more closely related to each other than are nivalis and henrici,
      despite that the latter two are often regarded as conspecific. The third distinct
      lineage within the snow finch complex consists of taczanowskii, which has been
      placed its own genus, Onychostruthus. This taxon has a basal position in the
      phylogenetic tree and is sister to all other snow finches. We estimated that
      taczanowskii split from the other taxa between 2 and 2.5 mya, i.e., about the
      time for the most recent uplift of the Tibetan plateau, "the Tibet movement", 3.6
      1.7 mya. Cladogenesis within the Montifringilla and Pyrgilauda clades seems to be
      contemporary with the second phase of "Tibet movement" at 2.5 mya and the third
      phase at 1.7 mya and "Kunhuang movement" in 1.5-0.6 mya. The dramatic climatic
      and ecological changes following from the uplift of the Tibetan plateau, together
      with the cyclic contraction and expansion of suitable habitats during the
      Pleistocene, are probably the most important factors for the cladogenesis in snow
      finch complex.

PMID- 16624594
TI  - Hares on thin ice: introgression of mitochondrial DNA in hares and its
      implications for recent phylogenetic analyses.

PMID- 16624595
TI  - Age-dependent effects on cisapride-induced QTc prolongation in the isolated
      guinea pig heart.
AB  - INTRODUCTION: The isolated guinea pig heart preparation has been suggested as a
      suitable small animal model for investigating potential for QTc prolongation. The
      purpose of this study was to investigate the effect of age on
      electrophysiological parameters measured in the isolated guinea pig heart
      preparation. In addition, the effect of a compound known to prolong the QT
      interval (cisapride) was investigated in both young and adult guinea pigs.
      METHODS: Male guinea pigs were divided into 2 groups (n=6). One group of guinea
      pigs was between 3 and 4 weeks old (young) and the other group was between 16 and
      17 weeks old (adult). Concentrations (0, 1, 5, and 50 ng/mL; 2, 11, and 110 nM)
      of cisapride were perfused for 15 min from low to high concentration.
      Measurements of PR, QRS, RR and QT intervals were typically made on 5 consecutive
      electrocardiogram complexes during the last minute of each concentration. The QT
      interval was corrected for changes in heart rate using the cube root formula of
      Fridericia (QTcF). RESULTS: Adult guinea pigs had significantly longer RR and
      QTcF intervals when compared to young animals. Cisapride prolonged QTcF in both
      young and adult animals at the same concentrations (5 ng/mL and 50 ng/mL). The
      maximal change in QTcF at 50 ng/mL was similar in young (44+/-3 ms) and adult
      animals (40+/-1 ms). DISCUSSION: In summary, the present study demonstrated that
      there was an increase in the RR and QTcF intervals with age in isolated guinea
      pig hearts. However, this age difference does not appear to impact the
      sensitivity of the assay to drug-induced QTcF prolongation.

PMID- 16624596
TI  - In vitro studies of DNA damage and its repair in cells from NHL patients with
      different p53 mutant protein status, resistant (p53(+)) and sensitive (p53(-)) to
      cancer chemotherapy.
AB  - INTRODUCTION: Resistance to an anthracycline-based regimen, such as CHOP,
      constitutes a problem for curing non-Hodgkin's lymphoma (NHL) patients.
      Chemoresistance in the clinic manifests itself as a lack of response to treatment
      or regrowth of a tumour after an initial response. METHODS: In this study,
      lymphocytes from NHL patients were treated with hydrogen peroxide (H(2)O(2)), a
      free radical generating model agent, and ethyl methanesulfonate (EMS), a model
      alkylating agent, to induce DNA damage which was evaluated by SCGE. This study
      assessed whether or not there were any differences in the patterns of damage and
      repair between cells from patients with p53 mutant protein abnormalities, i.e.
      over-expression (p53(+)) not responding to the CHOP regimen and patients
      responding to the CHOP regimen without p53 protein abnormalities (p53(-)) by
      comparison with control individuals (wild-type). An NHL cell line model [Raji
      TK(+) (mex(+)) and TK(-) (mex(-))] with p53 over-expression was also
      investigated. RESULTS: Results showed that frozen/thawed samples from healthy
      people were not suitable for use in repair studies, whilst fresh samples or
      samples incubated for 20 h at room temperature could be used. Tumour cells were
      more sensitive to damage than control cells. After treatment with H(2)O(2), cells
      from fresh or incubated blood showed a similar repair capacity. After treatment
      with EMS, there was a difference between repair in resistant and sensitive cells.
      DISCUSSION: These results suggest that the repair process is a useful cellular
      biomarker for investigating chemoresistance. The lack of repair in p53(+) cells
      may correlate with a low level of MGMT, since there was no repair in the Raji TK(
      ) cells lacking this enzyme.

PMID- 16624598
TI  - Genetics of restless legs syndrome.
AB  - Several studies on restless legs syndrome (RLS) have suggested a substantial
      genetic contribution in the etiology of this sleep disorder. Clinical surveys of
      idiopathic RLS patients have shown that 40-90% report a positive family history.
      The clinical features have been compared between familial and sporadic cases and
      the only difference found was a younger age-at-onset in familial RLS. Despite
      several reports suggesting a genetic contribution to the etiology of idiopathic
      RLS, few molecular genetic studies have been carried out attempting to identify
      genes that can predispose to this disorder. In particular, genes encoding for the
      GABA A receptor subunits, the gene for the alpha1 subunit of the glycine
      receptor, and genes involved in dopaminergic transmission and metabolism have
      been analyzed, however no significant findings have been reported. Genomewide
      linkage analysis studies using microsatellite markers have identified three loci
      for RLS: on chromosome 12q, on chromosome 14q and on chromosome 9p. It is
      important to investigate whether further RLS families show linkage to one of
      these loci to discuss the contribution of these loci and to provide a
      prerequisite of a mutational screening and identification of the RLS genes.

PMID- 16624599
TI  - Prevalence and genotyping of hepatitis E virus in swine population in Korea
      between 1995 and 2004: a retrospective study.
AB  - Hepatitis E virus (HEV) infections have been reported in pigs throughout the
      world but have only recently been recorded in Korean pigs. The aim of this study
      was to investigate whether HEV was present in archived porcine hepatic tissues
      collected between 1995 and 2004 using RT-PCR and immunohistochemistry and, if so,
      to determine the genotype of the isolates. Swine HEV was identified in the liver
      tissue of 42 pigs of 388 submissions (four pigs every year on average). The
      isolates showed genetic homology with swine and human HEV isolates identified in
      the United States and Japan (92.5-97%) and phylogenetic tree analysis indicated
      they belonged to genotype III. The study indicates that HEV is not a newly
      emerging virus in Korean pigs, but a pathogen that has existed in the country
      since at least 1995.

PMID- 16624600
TI  - Fibrin sealant as a treatment for canine aural haematoma: a case history.
AB  - Aural haematomas occur commonly in dogs in which predisposing factors include
      trauma to the pinna, a history of violent head shaking, and acute or chronic
      otitis externa. Treatment usually involves invasive surgery performed under
      general anaesthesia but these techniques can create wounds requiring intensive
      aftercare. Furthermore, certain breeds of dog and/or older animals are often at
      greater risk due to complications arising from the use of anaesthetics.
      Therefore, a need exists for a less invasive procedure which can be performed
      easily in general practice and with minimal reliance on anaesthetics. Fibrin
      sealants fulfil these criteria and have been used successfully to treat aural
      haematomas in humans. This is the first known report on the use of fibrin sealant
      to treat a canine aural haematoma. In the present case, the haematoma recurred
      shortly after removal of the protective collar, and was subsequently treated by
      conventional surgery. Possible reasons for initial success of the fibrin sealant
      and then later recurrence of the haematoma (e.g. premature removal of the collar)
      are discussed.

PMID- 16624601
TI  - Classification of patients with pain based on neuropathic pain symptoms:
      comparison of an artificial neural network against an established scoring system.
AB  - Wider use of pain assessment tools that are specifically designed for certain
      types of pain--such as neuropathic pain--contribute an increasing amount of
      information which in turn offers the opportunity to employ advanced methods of
      data analysis. In this manuscript, we present the results of a study where we
      employed artificial neural networks (ANNs) in an analysis of pain descriptors
      with the goal of determining how an approach that uses a specific symptoms-based
      tool would perform with data from the real world of clinical practice. We also
      used traditional statistics approaches in the form of established scoring systems
      as well as logistic regression analysis for the purpose of comparison. Our
      results confirm the clinical experience that groups of pain descriptors rather
      than single items differentiate between patients with neuropathic and non
      neuropathic pain. The accuracy obtained by ANN analysis was only slightly higher
      than that of the traditional approaches, indicating the absence of nonlinear
      relationships in this dataset. Data analysis with ANNs provides a framework that
      extends what current approaches offer, especially for dynamic data, such as the
      rating of pain descriptors over time.

PMID- 16624602
TI  - Why women prefer epidural analgesia during childbirth: the role of beliefs about
      epidural analgesia and pain catastrophizing.
AB  - This study investigated the reasons that might lead women to choose or not choose
      epidural analgesia as a strategy for the management of pain in childbirth. In our
      sample 55% of 114 women chose EA. Logistic regression resulted in a statistical
      model with four unique and independent predictors: Parity status and the fear of
      the side effects of EA each reduced the odds of choosing EA by half, whereas the
      desire to have a pain-free childbirth and positive experiences with EA of family
      and friends each doubled the odds of choosing EA. Pain catastrophizing was not
      related to EA use. The lack of an interrelationship between pain catastrophizing
      and EA use is probably due to an ambivalent attitude towards EA in pain
      catastrophizers. Pain catastrophizing was positively associated with the fear of
      being overwhelmed by labour pain and tendencies to avoid the pain, but also
      positively with the fear of pain during the insertion of the EA needle. Pain
      catastrophizing was also strongly related to recommendations to use EA from
      others, in particular from the midwife and from the gynecologist. Results are
      discussed in terms of the social impact of pain catastrophizing.

PMID- 16624603
TI  - Visceral obesity, impaired glucose tolerance, metabolic syndrome, and growth
      hormone therapy.
AB  - Overweight adults with impaired glucose tolerance have a 5-10% risk of developing
      diabetes per year, and insulin resistance is an important cause of progression to
      diabetes in these individuals. Weight loss has been shown to improve insulin
      sensitivity and prevent or delay progression to diabetes. According to recent
      studies, the improvement in insulin sensitivity that occurs with weight loss is
      closely linked to the reduction of visceral adipose tissue (VAT), the collection
      of intra-abdominal adipose depots that includes omental and intrahepatic fat.
      After controlling for BMI, whole body fat, and subcutaneous fat, only VAT is an
      independent predictor of endogenous insulin sensitivity and glucose tolerance
      before or after weight loss. This, in turn, suggests that reducing VAT is crucial
      to improving insulin sensitivity and preventing diabetes in high-risk
      individuals. Recombinant human growth hormone (GH) is a lipolytic drug that
      reduces total body, abdominal, and visceral fat in growth hormone-deficient (GHD)
      adults. Several studies have reported substantial reductions in VAT following GH
      treatment in this population. Like GHD adults, abdominally obese individuals have
      increased VAT, insulin resistance, and growth hormone levels that are below
      normal during continuous 24-h monitoring. These similarities have prompted a
      number of recent investigations in abdominally obese adults that reported
      significant reductions in truncal and visceral fat and an improvement in insulin
      sensitivity following prolonged GH administration. However, other studies have
      shown that insulin resistance and glucose concentrations transiently worsen
      during the first few weeks of GH treatment and that these deleterious effects can
      persist even after VAT reduction has occurred. Prior studies involving GH
      treatment were generally limited to adults who were normoglycemic at baseline.
      Less is known about the effects of GH in adults with impaired glucose tolerance
      or diabetes. The effects of GH used in conjunction with insulin sensitizers on
      glycemic control and VAT in patients with impaired glucose tolerance will be
      reviewed.

PMID- 16624604
TI  - Growth hormone dosing variables in growth hormone-deficient adults.
AB  - The use of growth hormone (GH) replacement for GH-deficient adults is now in its
      10th year of FDA-approved use in the United States; it has been used for a longer
      period of time in some European countries. Despite widespread experience, there
      is still lack of consensus regarding the best approach to GH initiation and
      titration in adults with growth hormone deficiency. Several factors must be
      considered prior to dose selection, including patient age, gender, symptoms, and
      the use and route of estrogen replacement therapy. We retrospectively examined GH
      dosing practices within our institution over a 5-year period to define GH dose
      requirements during the initial titration and maintenance phases, the frequency
      of dose adjustments, and the reasons behind the dose adjustments in young and
      older adults. Based on this review, we offer practical recommendations for
      endocrinologists in the management of adults with hypopituitarism and long-term
      GH treatment.

PMID- 16624605
TI  - Impact of treatment with recombinant human GH and IGF-I on visceral adipose
      tissue and glucose homeostasis in adults.
AB  - Supraphysiological doses of growth hormone (GH) therapy are generally thought to
      antagonize the effects of insulin, whereas the insulin-like growth factor I (IGF
      I) potentiates insulin-like actions. Paradoxically, adults with GH deficiency and
      patients with acromegaly are both predisposed to glucose intolerance and insulin
      resistance; however, one cannot extrapolate from these pathological conditions to
      determine the true metabolic roles of GH and IGF-I in glucose homeostasis. Growth
      hormone also promotes lipolysis, which has been shown to be the principal
      determinant of its insulin-antagonistic properties; on the other hand, IGF-I,
      which acts as an insulin sensitizer, does not exert any direct effect on
      lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing
      effect of IGF-I is evident only after feeding, when the bioavailability of
      circulating IGF-I is increased. In contrast to supraphysiological GH doses, low
      doses of GH treatment have been shown to increase circulating IGF-I levels and
      IGF-I bioavailability and, thus, may theoretically enhance insulin sensitivity
      without inducing lipolysis. We have recently reported that a fixed administration
      of a very low GH dose (1.7 microg/kg/day or 0.1mg/day) improved insulin
      sensitivity in adults with GH deficiency and increased peripheral glucose uptake
      in subjects with impaired glucose tolerance and the metabolic syndrome. Our data
      raise the possibility that this very low GH dose may play a role in maintaining
      beta-cell function and possibly delay the progression to type 2 diabetes in these
      high-risk patients.

PMID- 16624606
TI  - Pathophysiology of radiation-induced growth hormone deficiency: efficacy and
      safety of GH replacement.
AB  - Radiation-induced growth hormone deficiency (GHD) is primarily due to
      hypothalamic damage. GH secretion by the pituitary may be affected either
      secondary to some degree of quantitative deprivation of hypothalamic input or, if
      the radiation dose is high enough, by direct pituitary damage. As a consequence,
      the neurosecretory profile of GH secretion in an irradiated patient remains
      pulsatile and qualitatively intact. The frequency of pulse generation is
      unaffected, but the amplitude of the GH pulses is markedly reduced. Over the last
      25 years, the final heights achieved by children receiving GH replacement for
      radiation-induced GHD have improved; these improvements are attributable to
      refinements in GH dosing schedules, increased use of GnRH analogues for radiation
      induced precocious puberty, and a reduced time interval between completion of
      irradiation and initiation of GH therapy. When retested at the completion of
      growth, 80-90% of these teenagers are likely to prove severely GH deficient and,
      therefore, will potentially benefit from GH replacement in adult life. Such long
      term GH treatment in patients treated previously for a brain tumor means that
      critical and continuous surveillance must be devoted to the risk of tumor
      recurrence and the possibility of second neoplasms.

PMID- 16624607
TI  - Investigation of cardiac status and bone mineral density in Turner syndrome.
AB  - This review highlights recent developments in the detection and management of
      congenital heart disease and osteoporosis in patients with monosomy X, or Turner
      syndrome (TS). Magnetic resonance angiography (MRA) using gadolinium as a
      contrast agent demonstrates a higher prevalence and greater diversity of
      congenital cardiovascular defects than previously recognized in TS. Almost 50% of
      girls and women with TS have marked tortuosity or ectasia of the aortic arch,
      suggesting that these individuals may be at greater risk for aneurysm formation
      or dissection and therefore require closer monitoring. MRA also reveals that
      major venous anomalies are common in TS, with partial anomalous pulmonary venous
      return and persistent left superior vena cava each found in about 13% of
      patients. MR imaging even without contrast is a valuable complement to routine
      cardiac ultrasound in detecting abnormalities of the aortic valve. Abnormal
      electrocardiographic findings, including prolongation of the QTc interval, have
      recently been documented in many individuals with TS. Conduction and
      repolarization abnormalities have not been associated with congenital anatomic
      defects and are as common in young girls as adults. The clinical significance of
      these electrophysiological findings is unknown at present, but attention to the
      ECG in TS is important, particularly in monitoring the QTc when prescribing drugs
      associated with QT prolongation. Patients with TS are at high risk for
      osteoporosis as a result of premature ovarian failure and intrinsic bone
      abnormalities specific to the syndrome. Low cortical bone mineral density (BMD)
      is apparent in prepubertal girls, and it remains low in adults, independent of
      estrogen treatment and other hormonal factors. The low mineralization of cortical
      bone in TS may be associated with a small increased fracture risk, but no
      treatments are known to increase cortical bone mineral content in TS. Trabecular
      BMD is normal in TS women who have received continuous estrogen treatment from
      their mid-teens, although areal densitometry scores may be misleadingly low in
      very small patients. However, young women with ovarian failure who have not
      received estrogen treatment for extended periods of time are at high risk for
      osteoporosis of trabecular bone of the spine, with associated compression
      fractures and height loss. Therefore, judicious management of estrogen therapy to
      prevent osteoporosis while minimizing estrogen-associated adverse events is a
      challenging aspect of care for girls and women with TS.

PMID- 16624608
TI  - Early, intracoronary growth hormone administration attenuates ventricular
      remodeling in a porcine model of myocardial infarction.
AB  - OBJECTIVE: Ventricular remodeling is a common corollary of myocardial infarction.
      We hypothesized that this process may be attenuated by growth hormone,
      administered as a single high-dose, selectively in the infarct zone, early
      postmyocardial infarction. DESIGN: In 35 pigs (29+/-4 kg), myocardial infarction
      was generated by inflation of an over-the-wire angioplasty balloon in the
      circumflex artery for 60 min and 5 further pigs were sham-operated. Ten minutes
      after reperfusion, the pigs were randomized (2:1) to either growth hormone (1
      IU/kg) (n=23) or normal saline (n=12), delivered via the balloon catheter. All
      survivors were treated with captopril and were sacrificed 4 weeks after
      myocardial infarction. RESULTS: Compared to controls, growth hormone-treated
      animals displayed lower heart weight (4.1+/-0.5 g/kg body weight, versus 3.4+/
      0.4 g/kg, respectively, p=0.003) and dimensions (left ventricular short axis
      diameter 46+/-7 mm versus 37+/-6 mm, p=0.01; right ventricular short axis
      diameter 38+/-7 mm versus 30+/-5 mm p=0.001). Growth hormone increased wall
      thickness in the infarct (6.0+/-1.8 in controls versus 9.9+/-3.7 in treated
      animals, p=0.004) and non-infarct zones (10.6+/-1.8 in controls versus 15.5+/-3.8
      in treated animals, p=0.0006) and produced higher (p<0.05) microvascular density
      in both zones. CONCLUSION: Intracoronary administration of growth hormone
      attenuates left and right ventricular remodeling by inducing hypertrophy and by
      enhancing angiogenesis.

PMID- 16624609
TI  - Renal osteodystrophy in children: a systemic disease associated with
      cardiovascular manifestations.
AB  - The increasing prevalence of chronic kidney disease (CKD) in the United States
      demands a closer evaluation of and attention to associated morbidities, and,
      particularly, the rising mortality related to cardiovascular disease in all age
      groups. Patients with CKD demonstrate an increased risk of coronary artery
      disease due to calcium deposition and subsequent arterial stiffening, in addition
      to left ventricular dysfunction with associated heart failure and arrhythmias.
      While clearly impacted by the traditional risk factors for development of
      cardiovascular disease (CVD), patients with CKD are also affected by non
      traditional risk factors, including calcium overloading related to aggressive
      management of secondary hyperparathyroidism. Recent data have shown that a
      substantial number of patients with CKD are deficient in vitamin D on a
      nutritional basis, in addition to the known decrease in the kidney-produced
      active metabolite during progressive CKD. Historically, vitamin D has been
      described as an endocrine hormone that regulates blood calcium and parathyroid
      hormone levels. It has become increasingly clear, through the recognition of a
      vitamin D receptor in most tissues, that vitamin D possesses functions well
      beyond calcium homeostasis, such that a deficiency may contribute to the
      development of CVD. In this brief review, the role of vitamin D activation
      through its vitamin D receptor will serve as an introduction to the magnitude of
      the nutritional deficits in children, adults, and those with CKD. As therapeutic
      entities in the management of renal osteodystrophy, vitamin D analogues play an
      important role in cardiovascular health that continues to evolve. Preliminary
      studies indicate that vitamin D therapy for control of secondary
      hyperparathyroidism may confer cardioprotection and reduce mortality. Attention
      to care of osteodystrophy in CKD must take into account heart health as well.

PMID- 16624610
TI  - Polymorphisms at fifteen tetrameric short tandem repeat loci in three ethnic
      populations of Bengal, India.
AB  - The study presents allele frequency data at 15 tetrameric short tandem repeat
      (STR) loci (D3S1358, THO1, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539,
      CSF1PO, vWA, D8S1179, TPOX, D2S1338, D19S433 and FGA) in three ethnic populations
      -Mahishya, Bauri and Namasudra of Bengal to evaluate their utility in Forensic
      testing and understanding population structure and dynamics. A total of 169
      individuals were studied from the selected populations. On an average the
      combined power of discrimination and power of exclusion in these groups was found
      0.97 and 0.99, respectively. The allele distribution pattern shows possible
      genetic admixture between these ethnic groups which could be attributed to their
      close geographical proximity and occupying almost similar position in the social
      hierarchy. This study suggests that the 13 Combined DNA Index System (CODIS)
      markers and two added markers named D2S1338, D19S433 are highly informative and
      therefore suitable in matching biological specimen in human identification and
      population genetic study.

PMID- 16624611
TI  - Assessing hip osteoarthritis severity utilizing a probabilistic neural network
      based classification scheme.
AB  - A computer-based classification system is proposed for the characterization of
      hips from pelvic radiographs as normal or osteoarthritic and for the
      discrimination among various grades of osteoarthritis (OA) severity. Pelvic
      radiographs of 18 patients with verified unilateral hip OA were evaluated by
      three experienced physicians, who assessed OA severity employing the Kellgren and
      Lawrence scale as: normal, mild/moderate and severe. Five run-length, 75 Laws'
      and 5 novel textural features were extracted from the digitized radiographic
      images of each patient's osteoarthritic and contralateral normal hip joint spaces
      (HJSs). Each one of the three sets of textural features (run-lengths, Laws' and
      novel features) was separately utilized for assigning hips into the three OA
      severity categories, by means of a probabilistic neural network (PNN) classifier
      based hierarchical tree structure. The highest classification accuracy (100%) for
      characterizing hips as normal, of mild/moderate or of severe OA was obtained for
      the novel textural features set. Additionally, the novel textural features were
      used to design a mathematical regression model for providing a quantitative
      estimation of OA severity. Measured OA severity values, as expressed by HJS
      narrowing, correlated highly (r=0.85, p<0.001) with the predicted values by the
      mathematical regression model. The proposed system may be valuable in OA-patient
      management.

PMID- 16624612
TI  - Laser-scan endoscope system for intraoperative geometry acquisition and surgical
      robot safety management.
AB  - In laparoscopic surgery, surgeons find particular difficulties related to the
      operation technique. Due to restricted view, lack of depth information from the
      monocular endoscope and limited degree of freedom, surgeons find their movements
      impeded. A support system that provides improved laparoscopic vision would help
      to overcome the difficulties. If real-time visualization of abdominal structures
      were feasible, more accurate procedures and improved quantitative evaluations in
      laparoscopic surgery might be possible. In this study, a laser-scan endoscope
      system was developed to acquire and visualize the shape and texture of the area
      of interest instantaneously. The intraoperative geometric information of
      deformable organ could be applied for robotic safety management via geometric
      computation of robot position and organ shape. Results of in vivo experiments on
      a pig liver verified effectiveness of the proposed system.

PMID- 16624613
TI  - A novel mutation for TAP deficiency and its possible association with
      Toxoplasmosis.
AB  - We describe two siblings (a male patient and his older sister) with a novel
      mutation in the peptide transporter associated to antigen processing (TAP). The
      index case presented with not only granulomatous skin lesions and recurrent sino
      pulmonary infections, often associated with this deficiency, but also a severe
      pulmonary toxoplasmosis. His toxoplasmosis and skin lesions were successfully
      treated.

PMID- 16624614
TI  - Human papillomavirus typing with GP5+/6+ polymerase chain reaction reverse line
      blotting and with commercial type-specific PCR kits.
AB  - BACKGROUND: Infection with human papillomavirus (HPV) is a necessary step in the
      progression to cervical cancer. Many methods for HPV testing are currently
      available, most developed to detect pools of HPV types. OBJECTIVES: To evaluate
      the HPV typing by molecular methods and to compare commercial kits with an
      established laboratory method. STUDY DESIGN: Eighty-four cervical samples found
      to be positive for HPV DNA by GP5+/6+-polymerase chain reaction-enzyme
      immunoassay-reverse line blotting (PCR-EIA-RLB) were re-tested with two
      commercial methods, INNO-LiPA and Amplisense HPV typing, able to identify the HPV
      type predicted by PCR-EIA-RLB in 76 and 67 samples, respectively. RESULTS: The
      INNO-LiPA assay revealed HPV DNA in 75/76 samples (98.7%; 95% CI, 0.93-0.99) that
      would contain HPV types identifiable by this assay. The Amplisense HPV assay
      revealed HPV DNA in 58/67 samples (86.6%; 95% CI, 0.76-0.93) containing HPV types
      detectable by this assay. For samples with a single infection, the unweighted
      kappa for concordance of HPV typing was 0.87 (95% CI, 0.78-0.97) for PCR-EIA-RLB
      versus INNO-LiPA, 0.94 (95% CI, 0.87-0.99) for INNO-LiPA versus Amplisense HPV,
      and 0.82 (95% CI, 0.70-0.94) for PCR-EIA-RLB versus Amplisense HPV typing. PCR
      EIA-RLB revealed 12 multiple infections, INNO-LiPA revealed 14, and Amplisense
      HPV revealed 5. The agreement among tests for samples with multiple infections
      was lower, giving kappa values of 0.44 (95% CI, 0.18-0.70) for PCR-EIA-RLB versus
      INNO-LiPA, 0.52 (95% CI, 0.19-0.85) for PCR-EIA-RLB versus Amplisense HPV and
      0.43 (95% CI, 0.12-0.74) for INNO-LiPA versus Amplisense HPV. CONCLUSIONS: In HPV
      positive samples, the agreement among tests for HPV typing was high for single
      infections but markedly lower for infections with multiple HPV types.

PMID- 16624615
TI  - Scavenger receptor class B Type I (SR-BI) assembles into detergent-sensitive
      dimers and tetramers.
AB  - High density lipoproteins (HDL) are protective against cardiovascular disease due
      to their important role in the reverse cholesterol transport (RCT) pathway. The
      selective transfer of cholesteryl ester (CE) from the HDL core to cells, the last
      step in RCT, is mediated by scavenger receptor class B type I (SR-BI). SR-BI is a
      heavily glycosylated cell surface receptor that is highly expressed in the liver,
      ovaries, testes and adrenal glands, where selective uptake of HDL-CE is most
      prevalent. Previous studies have shown that SR-BI oligomerizes with itself in
      steroidogenic tissues as well as in diverse cell lines. In the present study, we
      provide further evidence for the homo-oligomerization of SR-BI. We show by FPLC
      and blue native PAGE that SR-BI forms complexes whose sizes suggest the formation
      of monomers, dimers, and tetramers. Interestingly, homo-oligomerization occurs
      even with the absence of SR-BI's C-terminal cytoplasmic domain. Finally, we
      report that an inhibitor of SR-BI-mediated cholesterol transport, BLT-1, and
      mutations in the putative leucine zipper region of SR-BI have profound effects on
      SR-BI function, however, they do not affect receptor self-association. These
      observations indicate that SR-BI homo-oligomerization occurs even when the
      receptor is non-functional.

PMID- 16624616
TI  - Phosphoinositide-specific phospholipase C (PI-PLC) beta1 and nuclear lipid
      dependent signaling.
AB  - Over the last years, evidence has suggested that phosphoinositides, which are
      involved in the regulation of a large variety of cellular processes both in the
      cytoplasm and in the plasma membrane, are present also within the nucleus. A
      number of advances has resulted in the discovery that phosphoinositide-specific
      phospholipase C signalling in the nucleus is involved in cell growth and
      differentiation. Remarkably, the nuclear inositide metabolism is regulated
      independently from that present elsewhere in the cell. Even though nuclear
      inositol lipids hydrolysis generates second messengers such as diacylglycerol and
      inositol 1,4,5-trisphosphate, it is becoming increasingly clear that in the
      nucleus polyphosphoinositides may act by themselves to influence pre-mRNA
      splicing and chromatin structure. Among phosphoinositide-specific phospholipase
      C, the beta(1) isoform appears to be one of the key players of the nuclear lipid
      signaling. This review aims at highlighting the most significant and up-dated
      findings about phosphoinositide-specific phospholipase C beta(1) in the nucleus.

PMID- 16624617
TI  - Phosphatidic acid- and phosphatidylserine-binding proteins.
AB  - Phosphatidic acid and phosphatidylserine are negatively charged abundant
      phospholipids with well-recognized structural roles in cellular membranes. They
      are also signaling lipids since their regulated formation (or appearance) can
      constitute an important signal for downstream responses. The list of potential
      effectors for these lipids is expanding rapidly and includes proteins involved in
      virtually all aspects of cellular regulation. Because it is not always clear
      whether these effectors recognize the specific phospholipids or a general
      negatively-charged membrane environment, questions about specificity must be
      addressed on a case by case basis. In this review we present an up to date list
      of potential phosphatidic acid- and phosphatidylserine-binding proteins.

PMID- 16624618
TI  - Plant fatty acid (ethanol) amide hydrolases.
AB  - Fatty acid amide hydrolase (FAAH) plays a central role in modulating endogenous N
      acylethanolamine (NAE) levels in vertebrates, and, in part, constitutes an
      "endocannabinoid" signaling pathway that regulates diverse physiological and
      behavioral processes in animals. Recently, an Arabidopsis FAAH homologue was
      identified which catalyzed the hydrolysis of NAEs in vitro suggesting a FAAH
      mediated pathway exists in plants for the metabolism of endogenous NAEs. Here, we
      provide evidence to support this concept by identifying candidate FAAH genes in
      monocots (Oryza sativa) and legumes (Medicago truncatula), which have similar,
      but not identical, exon-intron organizations. Corresponding M. truncatula and
      rice cDNAs were isolated and cloned into prokaryotic expression vectors and
      expressed as recombinant proteins in Escherichia coli. NAE amidohydrolase assays
      confirmed that these proteins indeed catalyzed the hydrolysis of 14C-labeled NAEs
      in vitro. Kinetic parameters and inhibition properties of the rice FAAH were
      similar to those of Arabidopsis and rat FAAH, but not identical. Sequence
      alignments and motif analysis of plant FAAH enzymes revealed a conserved domain
      organization for these members of the amidase superfamily. Five amino-acid
      residues determined to be important for catalysis by rat FAAH were absolutely
      conserved within the FAAH sequences of six plant species. Homology modeling of
      the plant FAAH proteins using the rat FAAH crystal structure as a template
      revealed a conserved protein core that formed the active site of each enzyme.
      Collectively, these results indicate that plant and mammalian FAAH proteins have
      similar structure/activity relationships despite limited overall sequence
      identity. Defining the molecular properties of NAE amidohydrolase enzymes in
      plants will help to better understand the metabolic regulation of NAE lipid
      mediators.

PMID- 16624619
TI  - Increased IFN-gamma production by NK and CD3+/CD56+ cells in sexually HIV-1
      exposed but uninfected individuals.
AB  - The mechanisms involved in controlling the establishment of HIV-1 infection are
      not fully understood. In particular, the role of innate immunity in natural
      resistance exhibited by individuals who are continuously exposed to HIV-1 but
      remain seronegative (ESN) has not been thoroughly evaluated. We determined the
      frequency and function of peripheral blood innate immune cells (plasmacytoid and
      myeloid dendritic cells, monocytes, NK cells, CD3+/CD56+ cells and invariant NKT
      cells) in ESN, chronically HIV-1-infected and low-risk HIV-1 seronegative
      individuals. ESN demonstrated a similar frequency of innate immune cells in
      comparison to controls and a higher frequency of dendritic cells, NK and
      invariant NKT cells compared to HIV-1-infected subjects. Incubation of
      mononuclear cells with stimulatory CpG ODN induced CD86 and CD69 up-regulation to
      a similar degree on innate cells from the three study groups. CpG ODN-stimulated
      secretion of cytokines was also similar between ESN and controls, while secretion
      of IFN-alpha was significantly decreased in HIV-1+ individuals. Importantly,
      expression of IFN-gamma by PMA/Ionomycin-activated CD56(bright) NK cells and
      CD3+/CD56+ cells was significantly higher in ESN when compared with controls. The
      anti-viral effects of IFN-gamma are well established, and so our results suggest
      that IFN-gamma production by innate immune cells might be one of the multiple
      factors involved in controlling the establishment of sexually transmitted HIV-1
      infection.

PMID- 16624620
TI  - Metabolic biotinylation provides a unique platform for the purification and
      targeting of multiple AAV vector serotypes.
AB  - The development of rationally designed targeted gene delivery vectors is an
      important focus for gene therapy. While genetic modification of AAV can produce
      vectors with modified tropism, incorporation of targeting peptides into the
      structural context of the AAV virion often results in loss of function or loss of
      virion integrity. To address this issue, we have developed a targeting system
      using metabolically biotinylated AAV. We generated serotype 1, 2, 3, 4, and 5 AAV
      capsids with small peptide insertions that are metabolically biotinylated in
      packaging cells during vector production by coexpression of the Escherichia coli
      BirA, biotin ligase, gene. Biotin moieties are exposed on the surface of
      assembled AAV particles and can interact with avidin. Metabolically biotinylated
      AAV vectors produced in this manner maintained endogenous titer and tissue
      tropism, could be purified on monomeric avidin resin, and could be retargeted to
      cells engineered to express an artificial avidin-biotin receptor. This technology
      provides not only a single platform for the purification of multiple AAV vector
      serotypes, but also a means for the development of multiple targeted AAV vectors
      utilizing a single capsid modification via straightforward avidin-biotin ligand
      coupling.

PMID- 16624621
TI  - Genotoxicity of retroviral integration in hematopoietic cells.
AB  - The experience of the past 3 years, since the first case of leukemia was reported
      in a child cured of X-linked severe combined immunodeficiency (X-SCID) by gene
      therapy, indicates that the potential genotoxicity of retroviral integration in
      hematopoietic cells will remain a consideration in evaluating the relative risks
      versus benefits of gene therapy for specific blood disorders. Although many
      unique variables may have contributed to an increased risk in X-SCID patients,
      clonal dominance or frank neoplasia in animal models, clonal dominance in humans
      with chronic granulomatous disease, and the ability of retroviral integration to
      immortalize normal bone marrow cells or convert factor-dependent cells to factor
      independence suggest that transduction of cells with an integrating retrovirus
      has the potential for altering their subsequent biologic behavior. The selective
      pressure imposed during in vitro culture or after engraftment may uncover a
      growth or survival advantage for cells in which an integration event has affected
      gene expression. Such cells then carry the risk that subsequent mutations may
      lead to neoplastic evolution of individual clones. Balancing that risk is that
      the vast majority of integration events seem to be neutral and that optimizing
      vector design may diminish the probability of altering gene expression by an
      integrated vector genome. Several cell culture systems and animal models designed
      to empirically evaluate the safety of vector systems are being developed and
      should provide useful data for weighing the relative risks and benefits for
      specific diseases and patient populations. Gene therapy interventions continue to
      have enormous potential for the treatment of disorders of the hematopoietic
      system. The future of such efforts seems bright as we continue to evolve and
      improve various strategies to make such interventions both effective and as safe
      as possible.

PMID- 16624622
TI  - Genetic correction of the fetal brain increases the lifespan of mice with the
      severe multisystemic disease mucopolysaccharidosis type VII.
AB  - Neurogenetic diseases typically have globally distributed lesions, and pathology
      usually develops early in life, requiring early diagnosis and treatment. We
      investigated the effects of transferring a corrective gene into the fetal brain
      before the onset of pathology in the mucopolysaccharidosis (MPS) type VII mouse,
      a model of a lysosomal storage disease. A single adeno-associated virus serotype
      1 vector injection into the ventricle at 15.5 days of gestation resulted in
      widespread distribution and lifelong expression of the normal gene in the brain
      and spinal cord. The normal enzyme was distributed to neighboring cells (as
      expected) and completely prevented the development of storage lesions throughout
      the central nervous system (CNS). No vector transfer was found outside the CNS,
      including the gonads, but a small amount of enzyme was present in visceral
      tissues, consistent with transfer from cerebrospinal fluid to venous circulation.
      The enzyme was present peripherally in such low amounts that it did not result in
      the severe skeletal dysmorphology that occurs readily when systemic treatment is
      used in neonates. However, the survival probability of the treated animals was
      significantly increased. The results suggest that the nervous system disease may
      contribute to the overall physiologic health of the animal in this type of
      disease.

PMID- 16624623
TI  - Serial cognitive change patterns across time after temporal lobe resection for
      epilepsy.
AB  - Longitudinal cognitive outcome with respect to general cognitive status and
      memory at the group and individual levels was studied 10 years after temporal
      lobe resection for epilepsy. Twenty-five patients who had undergone a medium-term
      follow-up (T2, median = 2.7 years) also underwent a long-term follow-up (T3,
      median = 9.8 years). At the group level, there was a significant increment across
      time, partly due to practice, in IQ (P value from 0.049 to <0.0001) but not in
      memory variables. On the basis of the normative interval of reassessed matched
      controls, the analysis at the individual level of change from baseline to T2
      disclosed decrements in 12-29% of the patients and increments in 8-21%. These
      proportions diminished at T3 (0-12 and 0-16%) and the dominating pattern of
      Performance IQ and verbal memory was a return toward baseline. These findings
      make the interpretation of an initial (T2) postoperative increment or decrement
      more problematic and underline the need for a comprehensive evaluation across
      time, including both at the group and individual levels.

PMID- 16624624
TI  - An evolutionary Michigan recurrent fuzzy system for nuclei classification in
      cytological images using nuclear chromatin distribution.
AB  - OBJECTIVE: The objective of this research is to carry out the classification of
      cellular nuclei in cytological pleural fluid images. The article focuses on the
      feature extraction and classification processes. The extracted feature is a
      spatial measurement of the chromatin distribution in cellular nuclei. The
      designed classifiers are fuzzy classifiers that carry out supervised
      classification. The classifier system's inputs are data series that represent
      these texture measurements. METHODS AND MATERIAL: The classifier is built on a
      Recurrent Fuzzy System (RFS). An evolutionary algorithm inspired by the Michigan
      approach is used to find an optimal RFS to classify different patterns expressed
      as data series. RESULTS: The effectiveness of the proposed classifier system is
      compared with other existing classification methods and evaluated via Receiver
      Operating Characteristic (ROC) analysis. We have obtained RFS based classifiers
      that perform with sensitivity values between 82.26 and 93.55% and with
      specificity values between 80.65 and 90.32%. The behavior of the proposed
      chromatin measurement is also compared with other texture measurements.
      CONCLUSION: The RFS based classifiers were successfully applied to the proposed
      data series that represent the chromatin distribution in cellular nuclei. These
      fuzzy classifiers present the highest classification efficiency and the ROC
      analysis confirms their suitable behavior.

PMID- 16624625
TI  - Classification of smoking cessation status with a backpropagation neural network.
AB  - This study examined the ability of a backpropagation neural network (BPNN)
      classifier to distinguish between current and former smokers in the 2000 National
      Health Interview Survey (NHIS) sample adult file. The BPNN classifier performance
      exceeded that of random chance, with asymmetric 95% confidence intervals for A(z)
      (area under receiver operating characteristic curve)=(0.7532, 0.7790). Separation
      of current and former smokers was imperfect, as illustrated by the receiver
      operating characteristic (ROC) curve. Additionally, performance did not exceed
      that of a comparison classifier created using logistic regression. Attribute
      subset selection identified three novel attributes related to smoking cessation
      status. This study establishes the ability of backpropagation neural networks to
      classify a complex health behavior, smoking cessation. It also illustrates the
      hypothesis-generating capacity of data mining methods when applied to large
      population-based health survey data. Ultimately, BPNN classifiers of smoking
      cessation status may be useful in decision support systems for smoking cessation
      interventions.

PMID- 16624626
TI  - Functional status of beta-2-adrenoceptor in isolated membranes of mature
      erythrocytes from patients with cirrhosis and oesophageal varices.
AB  - Propranolol is a widely used drug for prophylaxis of variceal bleeding in
      patients with cirrhosis, but not all patients show an adequate clinical response.
      This variability may be in relation to beta adrenoceptor activity, but no
      information is available in this setting. Thirty-nine patients with advanced
      cirrhosis and presence of oesophageal varices were sequentially included. We
      studied the function of beta-2-adrenoceptor in isolated membranes of mature
      erythrocytes obtained from patients by measuring cyclic AMP (cAMP) production
      before and after isoproterenol. Blood samples obtained from 11 healthy volunteers
      were used as control. Patients showed a six-fold increase in the mean basal cAMP
      production as compared to healthy volunteers. Isoproterenol produced a small, non
      significantly and highly variable increase in the AC activity in patients
      compared with controls. cAMP values remain stable after three months of
      continuous treatment with oral beta-blockers in both groups. Patients without
      antecedent of variceal bleeding or with an active alcohol intake showed a
      significantly higher isoproterenol effect. In conclusion, beta-receptor function
      in human erythrocytes membranes is altered in patients with cirrhosis and
      oesophageal varices.

PMID- 16624627
TI  - Mechanisms of agonist-induced constriction in isolated human mesenteric arteries.
AB  - We determined the calcium signalling pathways involved in the mechanisms of
      contraction of the vasoconstrictive agonists KCl, U46619 and PDBu in isolated
      human mesenteric arteries. The influence of gender, vessel diameter and age of
      the patients was also investigated. Human mesenteric arteries (n = 76) were
      loaded in a wire myograph and maintained at a tension equivalent to the in vivo
      pressure of 100 mm Hg, bubbled with 95%O2/5%CO2 to maintain pH 7.4 in
      physiological saline solution (PSS). Cumulative concentration-response curves
      were obtained to KCl (100 microM-100 mM), U46619 (1 nM-1 microM) or PDBu (1 nM-1
      microM), before or after a 30 min incubation with either the voltage-gated
      calcium channel (VGCC) blocker nifedipine (10 microM), the store-operated calcium
      channel (SOCC) blocker SK&F96365 (50 microM) or in calcium-free PSS (-Ca2+ PSS).
      The KCl response was abolished in -Ca2+ PSS and with nifedipine. The U46619
      response was partially blocked in -Ca2+ PSS and with nifedipine and predominantly
      blocked by SK&F96365. Incubation in -Ca2+ PSS had no effect on the response to
      PDBu. Arteries from male patients responded significantly higher to KCl than
      arteries from female patients. This study demonstrates that KCl induces
      mesenteric vasoconstriction via activation of VGCCs, U46619 induces mesenteric
      vasoconstriction via activation of SOCCs, but also VGCCs and PDBu induce
      mesenteric vasoconstriction via a calcium-independent pathway.

PMID- 16624628
TI  - Specific impairment of endothelium-derived hyperpolarizing factor-type relaxation
      in mesenteric arteries from streptozotocin-induced diabetic mice.
AB  - We hypothesized that the contribution made by endothelium-derived hyperpolarizing
      factor (EDHF) to acetylcholine (ACh)-induced endothelium-dependent relaxation
      (EDR) might be altered in mesenteric arteries from streptozotocin (STZ)-induced
      diabetic mice. In endothelium-intact preparations, the ACh-induced EDR (but not
      the sodium nitroprusside-induced relaxation) was weaker in the STZ group than in
      age-matched controls. Indomethacin (10 muM) had no significant effect on EDR in
      either group, indicating that cyclooxygenase products, including prostacyclin,
      are not involved. This indomethacin-resistant EDR was weaker in the STZ group
      than in the controls. To isolate the EDHF-resistant component of EDR,
      charybdotoxin (100 nM) and apamin (100 nM) were present in the bath solution
      throughout the next experiment. This EDHF-resistant relaxation did not differ
      significantly between the two groups. On the other hand, the EDHF-mediated
      relaxation was significantly weaker in the STZ group than in the controls, and it
      was completely blocked by lysophosphatidylcholine (LPC, 10 microM) in each group.
      The eNOS protein expression was similar between the two groups. These results
      suggest that (a) the endothelial dysfunction present in mesenteric arteries from
      type 1 diabetic mice is largely attributable to reduced EDHF signaling, and (b)
      LPC may be involved in this attenuation of EDHF-mediated relaxation.

PMID- 16624629
TI  - TGF-beta1-induced thrombospondin-1 expression through the p38 MAPK pathway is
      abolished by fluvastatin in human coronary artery smooth muscle cells.
AB  - Thrombospondin-1 (TSP-1) and transforming growth factor-beta1 (TGF-beta1) are
      both implicated in the pathogenesis of in-stent restenosis. This study evaluated
      the hypothesis that the HMG-CoA reductase inhibitor fluvastatin inhibits TGF
      beta1 induced TSP-1 expression via inhibition of p38 mitogen activated protein
      kinase (MAPK) phosphorylation in human coronary artery smooth muscle cells
      (HCASMC) and may therefore have anti-restenosis potential. Fluvastatin
      significantly reduced TSP-1 mRNA and protein expression in HCASMC in a
      concentration-dependent manner with a significant reduction in expression
      observed after treatment with 0.25 microM fluvastatin. TGF-beta1 (5 ng/ml)
      induced phosphorylation of p38 MAPK and induced TSP-1 mRNA and protein expression
      in HCASMC. Fluvastatin abolished TGF-beta1-induced phosphorylation of p38 MAPK
      and TGF-beta1-induced TSP-1 expression. Blockade of the p38 MAPK pathway with the
      upstream inhibitor SB-203580 also abolished TGF-beta1-induced TSP-1 expression.
      We conclude that fluvastatin decreases expression of TSP-1 and abolishes the
      ability of TGF-beta1 to induce TSP-1 expression in HCASMC; this may be achieved
      by preventing signalling through the p38 MAPK pathway. Targeted delivery of
      fluvastatin may therefore be a useful therapeutic objective for prevention of the
      intimal hyperplasia associated with in-stent restenosis.

PMID- 16624630
TI  - Renoprotective effects of fenofibrate in diabetic rats are achieved by
      suppressing kidney plasminogen activator inhibitor-1.
AB  - To investigate mechanisms of protective effects of fenofibrate on the diabetic
      kidney, male Wistar rats were divided into control, untreated diabetes, and
      fenofibrate-treated (32 mg kg(-1) d(-1), 8 weeks) diabetes groups. Diabetes
      induced by streptozotocin (25 mg/kg) and a high-fat diet was characterized by the
      disorders of plasma glucose and lipids. In untreated diabetic rats, there were
      increases in glomerular volume, matrix content, expressions of laminin and
      urinary albumin excretion. These nephropathies were associated with the
      upregulations of plasminogen activator inhibitor 1 (PAI-1) mRNA expression and
      its protein activity in the renal cortex, and a significant increase in
      transforming growth factor beta1 (TGF-beta1) expression. Treatment with
      fenofibrate suppressed the expression of PAI-I mRNA and its protein activity, and
      inhibited TGF-beta1 overexpression. It also partially reversed metabolic
      disorders and pathophysiologic changes associated with diabetic nephropathy. Our
      results indicate that fenofibrate delays the progression of diabetic nephropathy
      in rats to some extent. These renoprotective effects are likely to be achieved
      through suppression of PAI-1 and TGF-beta1 in the renal cortex, and consequently
      less extracellular matrix deposition.

PMID- 16624631
TI  - Systematic identification and classification of adverse events in human research.
AB  - Widely accepted standards and safeguards for research participants now include
      systematic surveillance and recording of adverse events. In the absence of a
      uniform regulation or structure for such reporting, each institution must now
      establish suitable yet efficient procedures to accomplish this task. We report
      herein our single center experience with a customized data collection, storage
      and review system specifically designed to identify and react appropriately to
      adverse events. Adverse events are classified by each investigator using three
      criteria in specific order: seriousness, expectedness and relatedness to the
      investigational intervention. Once classified, events are entered into an online
      database that includes collation, retrieval and search capabilities. Events
      meeting specified criteria are reviewed and adjudicated on a weekly basis by The
      University of Connecticut Research Adverse Events Committee, which makes advisory
      recommendations to the hospital's two Institutional Research Boards ranging from
      modification of informed consent to study suspension. Three hundred and seventy
      one serious adverse events from > 900 studies were reviewed in the previous
      academic year. Our system, which combines timely on-line reporting with regular
      surveillance, provides a potential model that meets the need for comprehensive
      yet practical adverse events assessment and reporting.

PMID- 16624632
TI  - Application of heat- and steam-generating sheets to the lumbar or abdominal
      region affects autonomic nerve activity.
AB  - Effects of applying a heat- and steam-generating (HSG) sheet on peripheral
      hemodynamics and autonomic nerve activity were examined. An HSG sheet was applied
      to the lumbar or abdominal region. Measurements included skin temperature at the
      lumbar and abdominal regions and the fingertip, total hemoglobin, tissue oxygen
      saturation ratio (StO2), pupillary light reflex, changes in ECG R-R interval
      blood pressure and percutaneous electrogastrography (EGG). A heat-generating
      sheet without steam was used as the control. Based on the present findings,
      application of the HSG sheet to the lumbar or abdominal region may improve
      peripheral hemodynamics and inhibit sympathetic nerve activity, resulting in
      parasympathetic nerve activity dominance.

PMID- 16624633
TI  - The challenge of real-time measurements of nitric oxide release in the brain.
AB  - Nitric oxide (NO) acts as a signalling molecule in the brain. NO has been
      implicated in a variety of central functions such as learning, plasticity and
      neurodegeneration. It is also involved in regulation of autonomic homeostasis at
      different levels of neuraxis including the nucleus tractus solitarii. In spite of
      the ample evidence for NO-mediated signalling many aspects of its mechanism of
      action the brain remain unknown largely due to the difficulties of NO detection
      in real time coupled with its unique ability to freely cross cellular membranes.
      Here we give a brief overview of the currently available options for NO detection
      in the brain (such as electrochemistry, fluorescent indicators, electron
      paramagnetic resonance) and consider some of their limitations. We conclude that
      it would be extremely useful to develop a highly sensitive probe for NO detection
      with some kind of build-in amplification which would magnify the changes
      triggered by NO to allow its detection within microdomains of the brain tissue in
      real time.

PMID- 16624634
TI  - Enteric neuroplasticity evoked by inflammation.
AB  - Neuroplastic changes in the enteric nervous system (ENS) may be observed in
      physiological states, such as development and aging, or occur as a consequence of
      different pathological conditions, ranging from enteric neuropathies (e.g.,
      Hirschsprung's disease) to intestinal (e.g., inflammatory bowel disease) or extra
      intestinal diseases (e.g., Parkinson's disease). Studying ENS plasticity may help
      to elucidate the pathophysiology of several diseases and have a bearing on the
      development of new pharmacological interventions. In the present review, we would
      like to focus on neuronal plasticity evoked by gastrointestinal inflammation
      occurring in inflammatory bowel disease and in a subset of patients with severe
      derangement of gut motility due to an enteric neuropathy characterized by an
      inflammatory infiltrate of the enteric plexuses. Major features of
      neuroplasticity within the enteric microenvironment encompass structural
      abnormalities ranging from nerve re-arrangement (e.g., hypertrophy and
      hyperplasia) to degeneration and loss of enteric ganglion cells; altered
      synthesis, content and release of neurotransmitters as well as up- or down
      regulation of receptor systems; gastrointestinal dysfunction characterized by
      sensory-motor and secretory impairment of the gut. Interestingly, neuronal
      changes may also occur in segments of the gastrointestinal tract remote from the
      site of the original inflammation, e.g. the ileum may show neuroplastic changes
      during colitis. Sometimes, the inflamed site may even be outside the gut. Among
      potential mechanisms underlying ENS plasticity, neurotrophins and enteric glia
      deserve special attention. A better comprehension of ENS plasticity during
      inflammation could be instrumental to develop new therapeutic options for
      patients with IBD and inflammatory enteric neuropathies.

PMID- 16624635
TI  - Baroreceptor reflex stimulation does not induce cytomegalovirus promoter-driven
      transgene expression in the ventrolateral medulla in vivo.
AB  - Adenoviruses are being employed to induce transgene expression in the central
      nervous system in vivo. In these studies, the cytomegalovirus (CMV) promoter is
      commonly employed to drive expression of the transgene because of its strong,
      constitutive activity in a wide range of cell types. However, using this
      promoter, expression in neurons is variable, with strongest expression being
      observed in non-neuronal cells. Indeed, even in vitro, CMV driven expression in
      neurons is variable. In cultured sympathetic ganglion cells it has been
      demonstrated that CMV-driven expression requires activation of cAMP-response
      element-binding protein (CREB) and that this can be induced by depolarization. In
      this study we tested whether depolarization might induce CMV-driven transgene
      expression, delivered by microinjection of an adenovirus, in the rostral
      ventrolateral medulla (RVLM) of rats. Prior to stimulation, transgene expression
      occurs in non-neuronal cells in the RVLM. Some neuronal expression was observed
      in neighbouring regions, in the nucleus ambiguus and in facial motor neurons.
      Within the RVLM, depolarization, induced by intraperitoneal administration of the
      ganglion blocking drug, pentolinium, did not lead to induction of transgene
      expression. This stimulus is known to induce expression of the immediate early
      gene c-fos. We conclude that either this experimental paradigm was not sufficient
      for activation of the CREB pathway or that possibly the virus does not gain
      access to the neurons of the RVLM. The adoption of specific promoters or viruses
      with higher neuronal transduction efficiency appears to be essential for the
      genetic modification of RVLM presympathetic neurons in vivo.

PMID- 16624636
TI  - Magnesium influences the discrimination and release of ADP by human RAD51.
AB  - hRAD51 lacks cooperative DNA-dependent ATPase activity and appears to function
      with 5-10-fold less Mg2+ compared to RecA. We have further explored the effect of
      Mg2+ on adenosine nucleotide binding, ATPase, and DNA strand exchange activities.
      hRAD51 was saturated with the poorly hydrolyzable analog of ATP, ATPgammaS, at
      approximately 0.08 mM Mg2+. In contrast, > 0.5 mM Mg2+ was required to saturate
      hRAD51 with ADP. We found ADP to be a significantly less effective competitive
      inhibitor of the hRAD51 ATPase at low Mg2+ concentrations (0.08 mM). Mg2+ did not
      appear to affect the ability of ATPgammaS to competitively inhibit the hRAD51
      ATPase. Low Mg2+ (0.08-0.12 mM) enhanced the steady-state ATPase of hRAD51 while
      higher Mg2+ concentration (> 0.3 mM) was inhibitory. At low Mg2+, hRAD51 appeared
      capable of nearly complete hydrolysis of available ATP, suggesting a lack of ADP
      product inhibition. There was a strong correlation between the amount of Mg2+
      required for stable ADP binding and the inhibition of hRad51 strand exchange
      activity. Simultaneous inclusion of exogenous ATP and chelation of Mg2+ with EDTA
      significantly enhanced ADP-->ATP exchange by hRAD51. These studies are consistent
      with the hypothesis that Mg2+ influences the discrimination and release of ADP,
      which may sequentially impose an important regulatory step in the hRAD51 ATPase
      cycle.

PMID- 16624637
TI  - Alginate-chaperoned facile refolding of Chromobacterium viscosum lipase.
AB  - Urea denatured lipase from Chromobacterium viscosum lipase could be refolded by
      addition of alginate with high guluronic acid content. The refolded molecule
      could be recovered by affinity precipitation. This approach resulted in recovery
      of 80% (of original activity) as compared to classical dilution method which gave
      only 21% activity recovery. Dynamic light scattering showed that binding required
      about 45 min and activity data obtained from affinity precipitation experiments
      indicated that refolding was almost instantaneous after binding. Circular
      dichroism (CD) and fluorescence data showed that refolded molecule was identical
      to the native molecule. It also showed that refolding takes place at the binding
      stage and not at the precipitation stage. Preliminary studies showed that the
      refolding strategy worked equally well with lipases from wheat germ and porcine
      pancreas.

PMID- 16624638
TI  - Ethics of scientific publication after the human stem cell scandal.

PMID- 16624639
TI  - Scientific and medical aspects of ozone therapy. State of the art.
AB  - The aim of this review is to dispel misconceptions and skepticism regarding ozone
      therapy and to clarify the biochemical and pharmacological mechanisms of action
      of ozone dissolved in biological fluids. The work performed in the last decade in
      our laboratory allows drawing a comprehensive framework for understanding and
      recommending ozone therapy in some diseases. It is hoped that this report will
      open a dialogue among clinical scientists and will inform physicians about the
      beneficial effects of ozone therapy.

PMID- 16624640
TI  - Oxidative stress at the vascular wall. Mechanistic and pharmacological aspects.
AB  - During the process of energy production in aerobic respiration, vascular cells
      produce reactive oxygen species (ROS). A growing body of evidence indicates that
      oxidative stress refers to a condition in which cells are subjected to excessive
      levels of ROS. Overall vascular function is dependent upon a fine balance of
      oxidant and antioxidant mechanisms, which determine endothelial functions.
      Considerable experimental and clinical data indicate that intracellular oxidant
      milieu is also involved in several redox-sensitive cellular signaling pathways
      such as ion transport systems, protein phosphorylation, and gene expression and
      thus also plays important roles as modulator of vascular cell functions such as
      cell growth, apoptosis, migration, angiogenesis and cell adhesion. Overproduction
      of ROS under pathophysiologic conditions is integral in the development of
      cardiovascular diseases. This fact has raised an intensive search of new
      pharmacological approaches to improve vascular hemostasis and particularly those
      intended to decrease oxidative stress or augment the antioxidant defense
      mechanisms.

PMID- 16624641
TI  - Cold preservation of pig liver grafts with warm ischemia and pentoxifylline-UW
      solution.
AB  - BACKGROUND: We undertook this study to investigate the safe time limits of cold
      preservation in UW solution of liver grafts subjected to warm ischemia (WI) for
      20 min and the changes of the limits when pentoxifylline is added to UW solution.
      METHODS: The safe time limit was studied in a simple porcine orthotopic liver
      transplantation (LTx) model. In donors, livers were subjected to 20 min of WI and
      subsequent 12-h (group 1, n = 5), 16-h (group 2, n = 5), and 20-h (group 3, n =
      3) cold preservation in UW solution, respectively. After the safe time limits
      were clear, another group (group 4, n = 5) was built to test whether or not the
      limits can be changed when pentoxifylline is added to UW solution in an unsafe
      time limit group. RESULTS: All five animals in group 1 survived up to 7 days of
      the survey endpoint. In group 2, only one animal survived up to the same survey
      endpoint and all animals in group 3 died within 12 h. The 1-week survival rate of
      group 1 was significantly higher than the other two groups. Group 1 had a lower
      level of alanine aminotransferase (ALT) or aspartase aminotransferase (AST) after
      LTx, less pathological damage, higher concentration of adenosine triphosphate
      (ATP) and higher microcirculation blood flux in the grafted liver tissue at 1 h
      after reperfusion than the other two groups. The results primarily showed that 12
      h cold preservation was safe, 16 h was unsafe, and 20 h was highly unsafe. But
      when pentoxifylline was added to UW solution in cold preservation (16-h group,
      group 4), in contrast to group 2, the incidence of liver tissue necrosis and
      primary graft nonfunction was significantly lower in group 4 than in group 2. The
      1-week survival rate of the pigs was 100% in the former and 20% in latter group.
      Levels of ALT and AST in recipients' artery blood, malondialdehyde and TNF-alpha
      concentration in grafted liver tissue, resistance of portal vein and hepatic
      artery after preservation in group 4 were significantly reduced, whereas
      microcirculation blood flux of the grafted liver, superoxide dismutase
      concentration and ATP concentration in grafted liver tissue were significantly
      elevated. CONCLUSIONS: The safe time limit of cold preservation in UW solution of
      liver grafts subjected to WI for 20 min was about 12 h and the limits can be
      prolonged to 16 h when pentoxifylline is added to UW solution. Many mechanisms
      were involved.

PMID- 16624642
TI  - C-reactive protein products generated by neutrophil elastase promote neutrophil
      apoptosis.
AB  - BACKGROUND: C-reactive protein (CRP), a prototypical acute phase protein, is
      increased as much as 1000-fold during acute inflammation, suggesting its
      biological role in that process. CRP can be modified at sites of inflammation
      where proteases have been released by neutrophils migrating to tissues. In this
      study, we investigated whether native CRP and neutrophil elastase-digested
      products of CRP modulate the rate of neutrophil apoptosis. METHODS: Neutrophils
      were isolated from venous blood of healthy volunteers and incubated with either
      native CRP (1, 10, or 30 microg/mL) or CRP digested with neutrophil elastase (1
      U/mL). After 6 and 24 h of incubation, neutrophils were harvested and examined
      for apoptosis under light microscopy. RESULTS: We found that CRP degradation
      products generated by neutrophil elastase, but not native CRP, promoted
      neutrophil apoptosis and cell death. The rate of apoptosis was not affected by
      the addition of elastase that was not incubated with CRP. CONCLUSIONS: These
      results suggest that CRP degradation products generated by neutrophil elastase
      promote neutrophil apoptosis. Cleavage of CRP by neutrophil elastase may offer
      protection from inflammatory injury.

PMID- 16624643
TI  - Immunoexpression of the HLA-DR class II molecule in cells from inflamed dental
      pulp.
AB  - BACKGROUND: Despite that the role of inflammatory cells in chronic inflammatory
      reactions of pulpal origin (CIRPOs) has been extensively studied, function of the
      HLA-DR+ cells (HLA-DR+ Cs) is poorly understood. The aim of this study was to
      quantify their number and clarify their role in these lesions. METHODS: We
      studied 11 CIRPOs immunostained with an anti-HLA-DR class II monoclonal antibody
      and the number and location of the HLA-DR+ Cs quantified. CIRPOs were divided in
      periapical granulomas (PGs), epithelized granulomas (EGs) and periapical cysts
      (PCs). RESULTS: HLA-DR+ Cs were observed within epithelium, inflammatory
      infiltrate and close to blood vessels. In PGs, they account for 19-256 cells/mm2,
      in EGs they were 20-494 cells/mm2 and in PCs quantification numbered 39-316
      cells/mm2. CONCLUSIONS: Our results suggest that HLA-DR+ Cs present antigens to
      lymphocytes, collaborating in initiation, regulation, development and
      perpetuation of CIRPOs. Also, these results suggest that these cells have an
      active role during initiation of epithelial proliferation in PGs and that they
      are partially responsible for cystic transformation from EGs to periapical cysts.
      They may also play an active role in bone resorption.

PMID- 16624644
TI  - Opsonic requirements for the respiratory burst of neutrophils against Giardia
      lamblia trophozoites.
AB  - BACKGROUND: Giardia lamblia is an important cause of parasitic diarrheal disease
      worldwide. Occasionally, polymorphonuclear neutrophils (PMNs) may participate as
      effector cells against Giardia lamblia. The present study was performed in order
      to examine the role of specific antibody and complement components in promoting
      the respiratory burst (RB) of PMNs against Giardia lamblia. METHODS: PMNs from
      human adult volunteers were incubated with Giardia trophozoites in the presence
      of non-immune (NS) or hyperimmune (HS) serum (anti-Giardia titer, >1:1024).
      Adherence was scored visually on coverslide after staining with Giemsa. The
      ability of Giardia to trigger the oxidative response of PMNs was measured by the
      anion superoxide (O2(-)) production using a cytochrome C reduction method and by
      the luminol amplified chemiluminescence (CL) assay. RESULTS: Incubation with NS
      or HS increased Giardia adherence to PMNs from 6.9 +/- 3.2% (basal adherence of
      Giardia incubated in buffer) to 39 +/- 18.6% (p <0.01) and 76 +/- 19.5% (p
      <0.001), respectively. In absence of serum, Giardia failed to trigger an
      oxidative response of PMNs. Opsonization with NS or HS increased the PMN O2(-)
      production from 3.9 +/- 0.92 nmol/2.5 x 10(6) PMNs/10 min to 9.04 +/- 1.68 (p
      <0.05) and 17.9 +/- 1.32 (p <0.001), respectively. A similar enhancement of the
      CL response was also observed. The inactivation of complement activity by heat as
      well as the elimination of specific antibodies by absorption produced a
      significant abrogation of the oxidative response but in the case of HS heat
      inactivation alone did not abolish the response. Similar findings (variable
      abrogation of the oxidative PMN response) were observed when PMNs were incubated
      with monoclonal antibodies directed against complement C3, C3b or the low
      affinity Fc receptors (CR1, CR3 or FcRlo). CONCLUSIONS: These results show that
      complement components and specific antibodies influence in the Giardia-PMN
      interaction. Although components of complement can contribute to the RB of PMNs,
      specific antibodies are critical for an optimal oxidative PMN response.

PMID- 16624645
TI  - Macrophage-activation inhibitor factor from L5178Y murine lymphoma and formation
      of hepatic abscesses in BALB/c mice.
AB  - BACKGROUND: Normal mice are naturally resistant to hepatic abscesses produced by
      Listeria monocytogenes. A macrophage-activation inhibitor factor (MAIF) isolated
      from the cell-free ascitic fluid of L5178Y lymphoma-bearing mice inhibited the
      lipopolysaccharide-induced production of nitric oxide (NO) by the macrophages.
      Because macrophages are also involved in the immune response towards L.
      monocytogenes, the present study had the objective of investigating whether MAIF
      was also capable of allowing L. monocytogenes to form hepatic abscesses. METHODS:
      BALC/c mice were inoculated intrahepatically with 5 x 10(5) bacteria.
      Experimental groups were treated daily with subcutaneous or intraperitoneal doses
      of 0, 1, 5 or 10 microg of MAIF/g of body weight. One dose was applied before
      inoculating bacteria and the remaining three doses 24, 48, and 72 h after
      inoculating bacteria. The development of hepatic abscess was analyzed 24 h after
      the last administration of MAIF. RESULTS: All treated mice (but not controls)
      developed hepatic abscess showing no differences regarding MAIF administration
      route. CONCLUSIONS: These results suggest a possible MAIF in vivo inhibition of
      NO macrophage production that allows L. monocytogenes hepatic abscess development
      in mice.

PMID- 16624646
TI  - Protective effect of Arthrospira maxima on fatty acid composition in fatty liver.
AB  - BACKGROUND: Arthrospira maxima has been widely used for nutritional purposes.
      Additionally, A. maxima has shown immunomodulator, antiviral, antioxidant,
      vasomotor and hypolipidemic effects in laboratory and animal studies. A. maxima
      prevents fatty liver induced by either carbon tetrachloride (CCl4) or fructose
      rich diet; however, the liver lipid composition in these models is not clearly
      known yet. The aim of this study was to evaluate the effects of A. maxima on the
      liver lipid profile in CCl4-induced steatohepatitis. METHODS: A single sublethal,
      intraperitoneal dose of CCl4 was administered to male Wistar rats fed a diet with
      or without 5% A. maxima. Liver lipids: total lipids, triacylglycerols, total
      cholesterol, free fatty acids, and thiobarbituric acid reactive substances were
      assessed 24 and 48 h after injury with CCl4. Additionally, triacylglycerols,
      total cholesterol and aspartate aminotransferase were evaluated in blood.
      RESULTS: Forty eight hours after CCl4 treatment, rats fed a diet without A.
      maxima had serum aspartate aminotransferase and liver triacylglycerols values
      that were, respectively, 2.2 and 1.4 times higher than those of animals receiving
      5% A. maxima in their diet. The same pattern was observed for liver free fatty
      acids and thiobarbituric acid reactive substances. The groups fed a diet with A.
      maxima and treated with CCl4 showed a higher saturated fatty acid liver content
      than the groups without A. maxima in their diet. The percentage of unsaturated
      fatty acids increased 48 h after CCl4 treatment, but its value was 0.5 times
      lower in the group receiving A. maxima than in the group fed without A. maxima.
      In the liver, all animals receiving A. maxima showed a trend towards a lower
      percentage of unsaturated fatty acids, despite the mentioned increase 48 h after
      CCl4 treatment. CONCLUSIONS: The results suggest that, in the fatty liver induced
      by CCl4, the hepatoprotective effect of A. maxima involves (a) an antioxidant
      mechanism and (b) a lower unsaturation of the liver fatty acids. The preventive
      effect of A. maxima on the liver lipid changes induced by CCl4 could be partially
      explained by its antioxidant action and the ability to increase the
      synthesis/release of nitric oxide, but not by its soluble dietary fiber.

PMID- 16624647
TI  - Reduced number and activity of circulating endothelial progenitor cells from
      patients with hyperhomocysteinemia.
AB  - BACKGROUND: Hyperhomocysteinemia (HHcy) contributes to atherosclerosis and
      coronary artery diseases by inducing endothelial cell injury and dysfunction.
      Recent studies provided increasing evidence that endothelial progenitor cells
      (EPCs) participated in ongoing endothelial repair. The changes of EPCs in
      patients with HHcy have not yet been elucidated. Therefore, we investigated the
      number and functional activity of EPCs in patients with HHcy. METHODS: Human EPCs
      were isolated and cultured from patients with HHcy (n = 30) and matched
      volunteers (n = 30). Circulating EPCs were enumerated as AC133+ KDR+ cells via
      fluorescence-activated cell sorter analysis. Additionally, EPC were expanded from
      human blood in vitro and identified by DiI-acLDL uptake and lectin staining by
      direct fluorescent staining under a laser scanning confocal microscope. EPC
      migration activities were determined by modified Boyden chamber assay. EPC
      adhesion assay was performed by replating cells on fibronectin-coated dishes and
      then counting adherent cells. RESULTS: A significant decrease was observed in
      circulating EPC (AC133+ KDR+ cells) numbers in patients with HHcy compared with
      control subjects (63.9 +/- 11.7 cells/mL vs. 91.5 +/- 14.2 cells/mL blood, p
      <0.01). In addition, the numbers of EPCs also decreased in patients with HHcy
      after ex vivo cultivation (36.1 +/- 6.5 vs. 51.5 +/- 8.3 EPCs/x200 field, p
      <0.01). Both circulating EPCs and differentiated EPCs were inversely correlated
      with total homocysteine levels. In addition, EPCs from patients with HHcy were
      significantly impaired in their migratory capacity and ability to adhere to
      fibronectin compared with controls. CONCLUSIONS: The present study demonstrated
      that EPC numbers and functional capacity were impaired in patients with HHcy.

PMID- 16624648
TI  - Body fat at birth and cord blood levels of insulin, adiponectin, leptin, and
      insulin-like growth factor-I in small-for-gestational-age infants.
AB  - BACKGROUND: Low birthweight has been associated with an increased risk of
      obesity, insulin resistance, and diabetes in adulthood. The aim of this study was
      to evaluate IGF-I, adiponectin, insulin levels, and body fat in small-for
      gestational-age (SGA) infants at birth. METHODS: We performed a transverse
      comparative study in SGA and appropriate-for-gestational-age (AGA) infants. The
      study was conducted at the Hospital of Gynecology and Obstetrics in Leon, Mexico.
      Weight, length, and percent of body fat were evaluated during the first 48 h of
      birth. Glucose, insulin, leptin, adiponectin, and IGF-I levels in cord blood were
      measured. RESULTS: We studied 100 infants (50 SGA and 50 AGA). A history of
      diabetes in a second-degree relative was higher in SGA infants than in AGA
      infants (48.0 vs. 30.0%, respectively; p = 0.03). Glucose, adiponectin, insulin
      and IGF-I levels were similar between the groups. Leptin levels and percentage of
      body fat were lower in SGA than AGA (15.3 vs. 23.4 ng/mL; p = 0.003, 11.1 vs.
      12.7%; p <0.001, respectively). Logistic regression analysis showed that length,
      percentage of body fat, and leptin levels were positively associated with
      birthweight. However, leptin levels were not independent of percentage of body
      fat. CONCLUSIONS: Low body fat and leptin levels, but no evidence of increased
      metabolic risk at birth, were found in SGA infants.

PMID- 16624649
TI  - Prognostic value of B-type natriuretic peptide in patients with acute coronary
      syndromes.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is released from the cardiac
      ventricles in response to increased wall tension in patients with heart failure.
      The significance of blood BNP in predicting cardiac death in patients with acute
      coronary syndromes (ACS) in Chinese patients is yet to be established. METHODS:
      Blood BNP concentration was measured in 106 ACS patients 1-3 days after onset of
      ischemic symptoms. Patients were followed-up for 6 months on mortality and other
      cardiovascular events. RESULTS: During the follow-up, cardiac death occurred in
      13 patients (non-survival group). Another 12 patients were hospitalized due to
      recurrence of ACS or heart failure. The mean blood BNP concentration in the non
      survival group was significantly higher than that of the survival group (median
      1132 vs. 116 ng/L, p <0.001). Multivariate logistic regression analysis
      incorporating age, gender, history of hypertension, diabetes, left ventricular
      ejection fraction, troponin I and therapeutic regimens indicated that BNP was an
      independent predictor of cardiac death in these patients (odds ratio = 21.19, 95%
      confidence interval 4.53-99.06, p <0.001). CONCLUSIONS: BNP is a useful parameter
      in predicting cardiac death in Chinese patients with ACS.

PMID- 16624650
TI  - Reduced pulmonary function in wind instrument players.
AB  - BACKGROUND: Wind instrument playing requires a strenuous respiratory activity.
      Previous studies investigating effect of wind instrument playing on pulmonary
      function are equivocal. METHODS: In the present study, 34 male, non-smoker wind
      players in a military band were compared with 44 healthy non-smoker males by
      pulmonary function testing. RESULTS: All spirometric values including forced
      expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), FEV1/FVC, peak
      expiratory flow rate, forced expiratory flow in 25, 50, 75% of FVC, and during
      the middle half of the FVC were found significantly diminished in wind players.
      The class of wind instrument, brass or wood, showed no significant differences.
      FVC was significantly and negatively correlated with duration of practice.
      CONCLUSIONS: It was concluded that pulmonary function in wind players might be
      diminished probably due to development of asthma or constant barotrauma during
      their playing. This fact should be considered in clinical evaluation of wind
      instrument players.

PMID- 16624651
TI  - Relationship between subclinical thyroid dysfunction and femoral neck bone
      mineral density in women.
AB  - BACKGROUND: Osteoporosis associated with thyroid dysfunction has been
      traditionally viewed as a secondary consequence of altered thyroid function, but
      there was recently a report about the direct effects of thyroid-stimulating
      hormone (TSH) on bone remodeling, which was mediated via the TSH receptor found
      on osteoblast and osteoclast precursor cells. Endogenous subclinical thyroid
      dysfunction seems to be an appropriate model to examine the direct effect of TSH
      on bone metabolism while ruling out the direct effect of thyroid hormone on bone
      metabolism. Thus, we aimed to investigate the relationship between subclinical
      thyroid dysfunction and bone mineral metabolism in women. METHODS: We enrolled
      413 women (mean age: 52.2 +/- 6.6 years) in our study. Serum levels of TSH, free
      T4 and the biochemical markers of bone turnover were measured by the standard
      methods. BMD at the lumbar spine and femoral neck were measured by dual energy X
      ray absorptiometry. RESULTS: Femoral neck BMD was significantly reduced both in
      the subclinical hyperthyroid group and in the subclinical hypothyroid group as
      compared with the euthyroid group (one-way ANOVA, p <0.001; post-hoc analysis, p
      = 0.041, p = 0.033). In contrast to the femoral neck BMD, the lumbar spine BMD
      showed no difference between the two groups. Additionally, serum calcium and
      alkaline phosphatase levels, urine deoxypyridinoline levels, and urine calcium to
      creatinine ratio showed no differences between the two groups. CONCLUSIONS: Women
      having subclinical hyperthyroidism and women with subclinical hypothyroidsm have
      reduced femoral neck BMD. Additional studies are required to elucidate the
      mechanism for this finding.

PMID- 16624652
TI  - Relation of antimyocardium antibodies to mortality in patients with acute
      myocardial infarction.
AB  - BACKGROUND: Antimyocardium antibodies (AMA) have been observed in patients with
      acute myocardial infarction (AMI). At present it is unknown if these AMA play a
      role in the pathogenesis of acute or chronic myocardial damage or if they are
      only produced as a result of tissue destruction, disappearing later without
      clinical manifestations. However, some studies have shown that patients with AMI
      and AMA have higher possibilities of presenting heart failure and death. The aim
      of the present study was to determine if there is an association (odds ratio, OR)
      between AMA and death in patients with AMI. METHODS: The design was a cross
      sectional study. One hundred patients with acute myocardial infarction were
      recruited consecutively at the Coronary Care Unit of the Hospital de
      Especialidades at La Raza National Medical Center, IMSS, Mexico City. IgG
      antimyocardium antibodies were identified using the enzyme-linked immunosorbent
      assay technique (ELISA). RESULTS: Of the 100 patients studied, 81 were males and
      19 females, with an average age of 58 +/- 11 years. Of the population studied,
      44% showed AMA. It was observed that patients with positive AMA had an OR for
      heart failure of 3.40 (CI 95% 0.97-12.5, p = 0.06) and for death of 7.94 (CI 95%,
      1.49-56.1, p = 0.003). This variable was analyzed with other confounding
      variables using logistic regression, and an OR of 11.8 (CI 95% 1.63-86.3, p =
      0.001) was obtained. CONCLUSIONS: AMAs were an independent predictive factor for
      mortality in patients with AMI.

PMID- 16624653
TI  - Association of increased cardiorespiratory fitness with low risk for clustering
      of metabolic syndrome components in asymptomatic men.
AB  - BACKGROUND: From a preventive aspect, it is especially important to investigate
      the lifestyle risk factors associated with cardiovascular disease (CVD). The
      purpose of this study was to determine the relationship of increasing metabolic
      syndrome (MS) components across increasing levels of estimated cardiorespiratory
      fitness (CRF) in asymptomatic young to middle-aged men. METHODS: We studied 449
      consecutive asymptomatic men (47 +/- 7 years) who underwent a maximal treadmill
      exercise test according to the Bruce protocol. Cardiorespiratory fitness (CRF)
      was divided into tertiles based on metabolic equivalents (METs). The following MS
      components were studied: 1) waist circumference > 102 cm; 2) serum triglycerides
      > or = 150 mg/dL; 3) HDL cholesterol levels of < 40 mg/dL; 4) fasting blood
      glucose (FBG) > or = 110 mg/dL or 5) blood pressure > or = 130/85 mmHg or treated
      hypertension. Multinomial logistic regression was used to investigate the
      relationship between clustering of MS components and CRF as determined by
      metabolic equivalents (METs). We used polytomous logistic regression to determine
      the likelihood of clustering of increasing components of metabolic syndrome with
      intermediate (2nd tertile) and low (1st tertile) levels of CRF as compared to
      those with highest levels of CRF (3rd tertile). RESULTS: Overall in the study
      population, zero, 1, 2 and > or = 3 (i.e., metabolic syndrome) risk factors for
      MS were observed in 29% (n = 129), 26% (n = 118), 22% (n = 98) and 23% (n = 104)
      men, respectively. The mean METS achieved in the study population was 10 +/- 2
      (range 4-20). Nearly half (49%) of individuals with the highest levels of CRF had
      no MS risk factors whereas only 18% of those with low CRF (METS < 9) had no MS
      risk factors. On the other end of the spectrum, the prevalence of MS (> or = 3 MS
      risk factors) increased significantly across decreasing levels of CRF (6, 22, 33%
      p < 0.0001 for trend). Multivariable polytomous logistic regression (adjusting
      for age, smoking, cholesterol-lowering therapy) demonstrated that individuals
      with low CRF (1st tertile of METS) compared to those with highest CRF had 3.1- (p
      = 0.001) and 11.8- (p < 0.0001) fold higher risk of having 2 and > or = 3 MS
      components, respectively. Similar results were observed when the analyses was
      repeated adjusting for Framingham risk score. CONCLUSIONS: Asymptomatic men with
      low levels of CRF have a greater likelihood for clustering of MS components and
      thus are at higher CVD risk. Further studies are needed to define the risk of
      cardiovascular disease in patients with intermediate levels of CRF and address
      which treatment strategies are most important given an individual's risk profile.

PMID- 16624654
TI  - Overdiagnosis of Entamoeba histolytica and Entamoeba dispar in Nicaragua: a
      microscopic, triage parasite panel and PCR study.
AB  - BACKGROUND: Based on stool microscopy, an E. histolytica/E. dispar prevalence of
      18.6% was found in Leon, Nicaragua about 10 years ago. Since then, new non
      microscopic methods have been developed to discriminate between pathogenic E.
      histolytica and nonpathogenic E. dispar. The main objectives of the present study
      were to evaluate the true prevalence of E. histolytica among individuals with
      diarrhea and to assess the diagnostic procedures carried out at the health center
      level. METHODS: A descriptive study was carried out on patients with diarrhea.
      Parasite detection was performed by conventional microscopy on native
      preparations or concentrated and stained specimens, Triage Parasite Panel and by
      PCR for both E. histolytica and E. dispar. RESULTS: In 134 individuals with
      diarrhea, the prevalence of intestinal parasites was 69% as detected by direct
      stool examination. E. histolytica/E. dispar was found in eight (6%) of the
      samples, but the health centers reported 24%. In the Triage Parasite Panel only
      one case of E. histolytica/E. dispar was found. Analysis by PCR showed E. dispar
      in ten (7.5%) and E. histolytica in two cases (1.5%). The detection of intestinal
      coccidia and Dientamoeba fragilis required additional staining methods.
      CONCLUSIONS: PCR results showed that E. histolytica is a rare finding in patients
      with diarrhea. At the health centers, E. histolytica, E. histolytica/E. dispar
      were clearly overdiagnosed, with the consequence of overtreatment.

PMID- 16624655
TI  - Overweight and obesity status among adolescents from Mexico and Egypt.
AB  - BACKGROUND: Obesity is on the rise among adults, adolescents and children
      worldwide, including populations living in developing countries. This study aimed
      to describe body mass index of adolescents from Mexico and Egypt and to evaluate
      non-nutritional correlates from two cohort studies. METHODS: Questionnaire data
      and weight and height measurements were collected in two large baseline studies
      in adolescents between 11 and 19 years old attending public school during the
      1998-1999 school year in Mexico (n = 10,537) and the 1997 school year in Egypt (n
      = 1,502). The authors compared body mass index and correlates stratified by sex
      and country through multivariate linear regression. RESULTS: Overall prevalence
      of overweight and obesity was 19.8 and 7.9%, respectively, among the Mexican
      adolescents and 12.1 and 6.2%, respectively, among the Egyptian adolescents.
      Based on U.S. Centers for Disease Control and Prevention (CDC) definition growth
      charts, for Mexico 18% of boys and 21% of girls were overweight and 11% of boys
      and 9% of girls were obese. In the Egyptian sample, 7% of boys and 18% of girls
      were overweight and 6% of boys and 8% of girls were obese. The most consistent
      correlates of body mass index in the Mexican population were age, years of
      education, smoking, vitamin intake and participating in sports, whereas the
      factors correlated among Egyptian adolescents were age and rural residence.
      CONCLUSIONS: Obesity and overweight are becoming a problem among Mexican and
      Egyptian youth. Information about the risk factors associated with excessive
      weight gain during the adolescent period is a first step towards proposing
      prevention strategies.

PMID- 16624656
TI  - Respiratory syncytial virus group A and B genotypes and disease severity among
      Cuban children.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of serious
      lower tract infections in infants. Comorbid conditions such as chronic diseases
      and prematurity have been associated with greater severity illness, but virus
      genotypes and disease severity is still unknown. METHODS: Forty selected strains
      of RSV group A and B from Cuban infants with acute respiratory disease (ARD) over
      five seasons were studied. Viral RNA was extracted and polymerase chain reaction
      (PCR) was carried out using direct primers directed to parts of the nucleoprotein
      (N) and fusion (F) genes, respectively. Amplicons were digested using restriction
      fragment length polymorphism (RFLP) to define the association between virus and
      disease severity. Disease severity was assessed as very mild, mild, moderate, and
      severe. RESULTS: Three of six known N genotypes were detected. NP4 and NP3 were
      found more frequently; moreover, it was difficult to establish a relationship
      between N genotypes and disease severity. Five genotypes in F gene were found:
      F1, F2, F5, F9 and F11; F9 and F11 were associated with very mild disease, but F1
      genotype appears to be associated with moderate to severe disease. CONCLUSIONS:
      At least five combinations of N and F genotypes circulated in the studied infants
      in Cuba. Patients with F1NP4 genotype showed moderate to severe disease.
      Relationship between genotypes and disease severity was established.

PMID- 16624657
TI  - Discrepancies in cancer mortality estimates.
AB  - Progress against cancer-associated mortality could be estimated by mortality
      rates. However, population-based measures may not be comparable to trends across
      time based on individual cases followed over time. For two leading cancer types
      (colorectal and lung and bronchus), the following were calculated from the
      Surveillance, Epidemiology, and End Results (SEER) Program survival matrix
      output: probability of death (PD) as the relative cumulative deaths in a cohort
      of cancer patients at 12-month intervals after the year of diagnosis, 5-year
      survival probability, and median survival time. Annual age-adjusted U.S.
      mortality rates were obtained from the National Center for Health Statistics
      (NCHS). Colorectal cancer PD 5-year (patients having survived up to 5 years after
      diagnosis) decreased 4.3% from 1985-1997, in contrast to a 20% decrease in the
      mortality rate during the same period. The mortality rate for lung and bronchus
      cancer sharply increased between 1973 and 1991 and was followed by a clear
      downward trend of 2.5% from 1991-1997, while its PD 5-year decreased by only
      0.79%. PD for specific cohorts at yearly intervals did not improve across time at
      comparable intervals; however, the mortality rate was clearly reduced for both
      anatomic sites. Survival and PD were, as expected, inversely related. Changes in
      median survival and 5-year survival probability were similar over time. Although
      the cancer mortality rate is a clear statistical end-point, inference of success
      by its falling trend alone could be unrelated to the SEER probability of death.

PMID- 16624658
TI  - Plasma levels of vascular endothelial markers in obstructive sleep apnea.
AB  - Although the link between obstructive sleep apnea syndrome and risk for
      cardiovascular disorders has yet to be fully described, the hypothetical
      involvement of endothelial dysfunction is pathophysiologically plausible. In
      order to test this hypothesis, we measured plasma levels of endothelial markers
      in 82 male subjects (41 subjects with obstructive sleep apnea syndrome and a 41
      subject control group). Obstructive sleep apnea syndrome patients presented
      higher circulating levels of intercellular cell adhesion molecule-1, E-selectin,
      and endothelin-1 than the control group. On the other hand, no differences were
      found in the von Willebrand factor. Levels of E-selectin and intercellular cell
      adhesion molecule-1 were significantly correlated to total oxygen desaturation.
      However, no significant correlation was found in either endothelin-1 or von
      Willebrand factor. We conclude that obstructive sleep apnea syndrome is
      associated with changes in levels of adhesion molecules, and that this could be
      the result of obstructive sleep apnea syndrome-induced hypoxia.

PMID- 16624659
TI  - Downregulation of selected cytokines in amebiasis.
AB  - A 220-kDa E. histolytica lectin is capable of downregulating some inflammatory
      cytokines (IL-5, IL-6, INF-gamma and TNF-alpha) and thus of inducing an overall
      anti-inflammatory Th-phenotype in leucocytes of selected, perhaps
      constitutionally predisposed, individuals irrespective of their HLA-DR3 profile
      (i.e., in this study patients long recovered from amebic abscess of the liver).
      This probably inhibited cytokine response pattern could increase the risk for
      developing amebic abscess of the liver in the course of invasive intestinal
      amebiasis.

PMID- 16624660
TI  - Hyperbaric oxygen as an adjunctive therapy for bilateral compartment syndrome,
      rhabdomyolysis and acute renal failure after heroin intake.
AB  - Heroin abuse causes various medical and surgical complications. We report a case
      of heroin-induced severe bilateral compartment syndrome complicated by
      rhabdomyolysis, acute renal failure and extremely elevated creatinine kinase. A
      30-year-old male heroin addict presented to the emergency department of Mount
      Vernon Hospital, Mount Vernon, New York complaining of severe pain and burning
      sensation in both legs and feet 1 day after abusing intravenous heroin. He had
      severe swelling and tenderness of both legs and feet. Laboratory data revealed
      tremendous elevation of creatine kinase (236,000 IU/L) consistent with
      rhabdomyolysis. Acute renal failure developed over subsequent days. Treatment
      consisted of fasciotomy, hyperbaric oxygen therapy (HBO2) and supportive therapy.
      The condition gradually improved over 4 weeks and the patient did not require
      dialysis or amputation.

PMID- 16624661
TI  - Rare association of chronic lymphocytic thyroiditis with dermatomyositis.
AB  - Autoimmune thyroid disease (AITD) has been associated with other autoimmune
      diseases such as chronic urticaria, insulin-dependent diabetes mellitus,
      Sjogren's syndrome, inflammatory bowel disease, rheumatoid arthritis, multiple
      sclerosis, systemic lupus erythematosus, psoriasis, ankylosing spondylitis, and
      dermatomyositis (DM). AITD is a common disorder affecting primarily women, and
      both genetic and environmental factors are included in its pathogenesis. DM is
      considered an autoimmune disease of the muscles and skin. Although AITD is the
      most common cause of hypothyroidism, to the best of our knowledge, only three
      cases of DM and AITD in the same patient have been reported in the last 40 years.
      We consider that both are developed from the same autoimmune background. Herein,
      we present a case of a 30-year-old man with a 4-year history of AITD who was
      diagnosed as suffering as well from DM.

PMID- 16624662
TI  - A simple questionnaire on sleep status in a healthy Japanese population.

PMID- 16624663
TI  - Introduction of human rotavirus vaccine in Latin America.

PMID- 16624665
TI  - Activation of neurons containing the enzyme nitric oxide synthase following
      exposure to an elevated plus maze.
AB  - The elevated plus-maze (EPM) is one of the most used animal models of anxiety.
      Exposure to the EPM activates brain regions related to anxiety/fear. Systemic or
      intra-dorsolateral periaqueductal gray (dlPAG) inhibition of nitric oxide
      synthase (NOS) induces anxiolytic effect in animals submitted to an EPM.
      Additionally, exposure to an innate fear stimulus, such as a live predator,
      activates neurons containing NOS in regions related to defensive behavior.
      Considering these pieces of evidence, the present study investigated if neurons
      containing NOS localized in regions related to anxiety/fear are also activated
      after exposure to an EPM. Male Wistar rats were exposed to the EPM for 15 min and
      2 h later their brains were removed and processed for c-Fos immunohistochemistry
      (a marker of neuronal functional activation) and NADPH-diaphorase histochemistry
      (NADPH-d; used to detect the presence of NOS neurons). Exposure to the EPM
      significantly increased double-stained cells (c-Fos + NADPHd positive neurons) in
      the parvocellular paraventricular (pPVN) and lateral (LH) hypothalamic nuclei,
      dlPAG and dorsal raphe nucleus (DRN), but not in the amygdaloid complex, bed
      nucleus of stria terminallis, dorsal premammillary nucleus of hypothalamus and
      inferior colicullus. These results suggest that exposure to an EPM activates NOS
      containing neurons in brain areas related to fear/anxiety.

PMID- 16624666
TI  - Serotoninergic activation of the basolateral amygdala and modulation of tonic
      immobility in guinea pig.
AB  - Tonic immobility (TI), also known as death feigning or animal hypnosis, is a
      reversible state of motor inhibition that is not only triggered by postural
      inversion and/or movement restraining maneuvers but also by repetitive
      stimulation and pressure on body parts. Evidence has demonstrated that the
      basolateral nucleus of the amygdala (BLA) is particularly associated with
      defensive behavior that involves the emotional states of fear and anxiety. In
      addition, some reports have demonstrated that serotonin (5-HT) released in the
      amygdala is increased during states of stress and anxiety, principally in the
      BLA. In the present study, we investigated the effects of serotonergic activation
      of the BLA on the duration of TI. The results showed that the microinjection of 5
      HT (3.0 microg) into the BLA decreased the duration of TI. Similarly, the
      administration of a 5-HT1A agonist (0.1 microg of 8-hydroxy
      dipropylaminotretalin) or 5-HT2 agonist (0.1 microg of alpha-methyl-5-HT) into
      the BLA reduced the TI duration. The effect of 5-HT2 agonist was reversed by
      pretreatment with a dose that had no effect per se (0.01 microg) of ketanserin (5
      HT2 receptor antagonists) into the BLA. Moreover, the activation of 5-HT1A and 5
      HT2 receptors in the BLA did not alter the spontaneous motor activity in the open
      field test. The results of the present study indicate that the serotonergic
      system of the BLA possibly produces a reduction in fear and/or anxiety that
      reduces the TI duration in guinea pigs, but this is not due to increased
      spontaneous motor activity induced by serotonergic activation, which might affect
      TI duration non-specifically.

PMID- 16624667
TI  - A neural network approach to motor-sensory relations during postural disturbance.
AB  - This study explored whether artificial neural networks (ANN) can be used to
      quantify the motor-sensory relationship during postural disturbance. An ANN model
      was constructed with seven mechanical stimuli to the visual, vestibular and
      somatosensory systems (i.e., head angular and linear accelerations, eye-target
      distance, ankle joint rotation and velocity, as well as normal and shear ground
      contact forces under the feet) as inputs, and electromyographic activities of
      tibialis anterior and gastrocnemius muscles as outputs. These inputs and outputs
      were directly measured during a sudden toes-up-down rotation of the supporting
      base in two groups of elderly subjects: people with peripheral neuropathy (NP)
      who have severe loss of mechanoreception in the sole of their feet and people
      without NP. The products of ANN weights were used in a summary statistic called
      the Q-value to estimate the contribution of each mechanical stimulus to sensory
      systems in determining each leg muscle activity. It was found that: (1) the
      stimuli to the vestibular system and/or ankle proprioceptors have greater
      contributions to leg muscle activities, especially the TA muscle, in people with
      NP than people without NP; (2) the stimuli to somatosensory receptors have the
      greatest contribution, and the stimuli to the vestibular system have the least
      contribution to both muscle activities in both groups. These findings are
      supported by previous studies and have demonstrated the potential of the Q-value
      concept in the ANN model in studying the motor-sensory relationship in human
      postural control.

PMID- 16624668
TI  - 'One night' sleep deprivation stimulates hippocampal neurogenesis.
AB  - Neurogenesis in the adult hippocampus can be up- or downregulated in response to
      a variety of physiological and pathological conditions. Among these,
      dysregulation of hippocampal neurogenesis has been recently implicated in the
      pathogenesis of depression. In addition, in animal models of depression, a
      variety of antidepressant treatments reverse that condition by increasing
      neurogenesis. As one night sleep deprivation is known to improve mood in
      depressed patients for at least 1 day, we investigated whether a comparable
      treatment may affect hippocampal neurogenesis in adult rats. Accordingly, rats
      were sleep-deprived by gentle handling for 12 h during their physiological period
      of rest, and were injected with bromodeoxyuridine 4 h and 2 h before the end of
      sleep deprivation. They were then perfused immediately thereafter, or after 15
      days and 30 days. We found that 12 h sleep deprivation significantly increased
      cell proliferation and the total number of surviving cells in the hippocampal
      dentate gyrus soon after sleep deprivation, as well as 15 days and 30 days later,
      in comparison to control rats allowed to sleep. No changes were instead found in
      the subventricular zone of the lateral ventricles, indicating that 12 h sleep
      deprivation selectively triggers neurogenic signals to the hippocampus. The
      present data include acute sleep deprivation among the conditions which
      upregulate hippocampal neurogenesis and raise the possibility that such response
      could be implicated in the beneficial effects elicited in depressed patients by
      one night sleep deprivation. Thus, the findings could contribute to the
      understanding of the intriguing relationship between depression and neurogenesis
      in the adult brain.

PMID- 16624669
TI  - Effect of a serotonin depleting regimen of 3,4-methylenedioxymethamphetamine
      (MDMA) on the subsequent stimulation of acetylcholine release in the rat
      prefrontal cortex.
AB  - The amphetamine analog 3,4-methylenedioxymethamphetamine (MDMA) is considered to
      be selectively neurotoxic to serotonergic nerve terminals. Although the long term
      effects of MDMA on serotonin (5-HT) terminals have been well studied, other
      potential neurochemical consequences associated with MDMA-induced 5-HT depletion
      have been less well investigated. In view of the cognitive impairments in human
      MDMA abusers and the role of acetylcholine (ACh) in learning and memory, it was
      of interest to determine the influence of a 5-HT depleting regimen of MDMA on
      subsequent stimulation of ACh release in the prefrontal cortex (PFC). Male rats
      received vehicle or MDMA (10 mg/kg, i.p. every 2 h for four injections) and
      underwent in vivo microdialysis 7 days later to assess the subsequent drug-
      (e.g., MDMA, 5-HT1A agonist) or stress- (e.g., tail pinch, presence of an
      intruder rat) induced stimulation of ACh release. The increase in the
      extracellular concentration of ACh in the PFC produced by MDMA (10 mg/kg, i.p.)
      was significantly less in rats previously exposed to the neurotoxic regimen of
      MDMA than that in control animals. In contrast, there was no difference in the
      magnitude of the stimulation of cortical ACh release elicited by the 5-HT1A
      agonist, 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT, 0.3mg/kg, s.c.),
      tail pinch (30 min) or the presence of an intruder rat (40 min) between control
      animals and animals previously exposed to a neurotoxic regimen of MDMA. These
      results suggest that although MDMA-induced 5-HT depletion diminishes subsequent
      MDMA-induced ACh release, there is little impact on cortical ACh release elicited
      by the stress of pain or the novelty of an environmental intruder.

PMID- 16624670
TI  - Geranylgeranylacetone, an inducer of HSP 70, attenuates REM sleep rebound after
      sleep deprivation.
AB  - The effect of pretreatment of geranylgeranylacetone (GGA), an inducer of heat
      shock protein (HSP) 70, on responses in sleep and core body temperature (Tcore)
      against sleep deprivation (SD) was examined in rats. After 3 days of GGA or
      vehicle injection, a 6-h period of SD was performed. During the recovery period,
      both rapid-eye movement (REM) and non-REM (NREM) sleep were increased in both GGA
      and vehicle-injected rats. However, in GGA-injected rats, REM-sleep rebound was
      significantly suppressed, while NREM-sleep rebound remained unaffected. In
      addition, the increase of Tcore caused by SD was also attenuated in GGA-injected
      rats. In the hippocampus, both SD and the GGA pretreatment induced an increase in
      the expression of HSP70 mRNA, indicating that the SD functions as a stress for
      hippocampal neurons and that the GGA induces HSP70 expression. The findings
      suggest that pretreatment with GGA suppresses REM sleep rebound and the response
      of Tcore against SD.

PMID- 16624671
TI  - GDNF family ligand receptor components Ret and GFRalpha-1 in the human trigeminal
      ganglion and sensory nuclei.
AB  - The occurrence of Ret and GFRalpha-1 receptors is shown by immunohistochemistry
      in the human trigeminal sensory system at pre-, postnatal and adult age. Receptor
      labeled neurons occur in both trigeminal ganglion and mesencephalic nucleus. In
      adult trigeminal ganglion, about 75% of Ret- and 65% of GFRalpha-1-labeled
      neurons are small- and medium-sized. The proportion of Ret+ and GFRalpha-1+
      trigeminal ganglion neurons in the adult is about 25 and 60%, respectively. The
      majority of Ret+ are double labeled for GFRalpha-1 and glial cell line-derived
      neurotrophic factor (GDNF). Most of the GFRalpha-1+ cells contain GDNF and about
      50% of them contain Ret. Triple labeling shows many Ret+/GDNF+/GFRalpha-1+
      neurons, but also a number of Ret-/GDNF+/GFRalpha-1+ and Ret+/GDNF-/GFRalpha-1+
      cells. Both Ret+ and GFRalpha-1+ neuronal subpopulations overlap with that
      containing calcitonin gene-related peptide. Ret+ pericellular basket-like nerve
      fibers occur in the adult trigeminal ganglion. Centrally, immunoreactivity is
      restricted to the spinal nucleus pars caudalis and pars interpolaris and to the
      mesencephalic nucleus. In adult specimens, Ret+ nerve fibers and puncta gather in
      the inner substantia gelatinosa. Ret+ neurons occur in the spinal nucleus and are
      more frequent in newborn than in adult subjects. Central GFRalpha-1+-labeled
      neurons and punctate elements are sparse. These findings support the involvement
      of GDNF and possibly other cognate ligands in the trophism of human trigeminal
      primary sensory neurons from prenatal life to adulthood, indicating a selective
      commitment to cells devoted to protopathic and proprioceptive sensory
      transmission. They also support the possibility that receptor molecules other
      than Ret could be active in transducing the ligand signal.

PMID- 16624672
TI  - Internally driven control of reaching movements: a study on a proprioceptively
      deafferented subject.
AB  - We investigated the possibility of controlling reaching movements on the sole
      basis of central mechanisms, i.e., without peripheral feedback on hand and target
      positions. A deafferented subject (GL) and control subjects reached with the
      unseen hand for a straight-ahead target that could be displaced laterally at
      movement onset. The shifted target was continuously or briefly lit, or not
      visible. In this latter condition, a beep from either side of subjects' head
      single-handedly signaled the change in the movement goal, so that movements could
      only be controlled through an internal representation of the memorised target
      position. Compared to controls, GL showed quantitatively similar corrections (77%
      of the target displacement, on an average) and similar reaction times to the
      target shift (mean = 516 ms), regardless of target visual information. These
      results highlight a remarkable capacity for controlling reaching movements on the
      sole basis of internally driven processes. On the other hand, trajectories in
      double-step trials differed drastically between GL and controls. Controls'
      trajectories were composed of two segments, the second of which brought the hand
      directly toward the displaced target. The patient produced three-segment, stair
      like trajectories. The first and third segments were mainly in the sagittal plane
      and the second segment was a vector-image of the lateral target shift. A control
      experiment showed that GL's trajectories were not the result of a voluntary
      strategy used to adjust movement trajectory in the absence of peripheral
      information on hand position. We suggest that GL's trajectories reflect a deficit
      in interjoint coordination in the absence of proprioception.

PMID- 16624673
TI  - BNST lesions aggravate behavioral despair but do not impair navigational learning
      in rats.
AB  - The bed nucleus of the stria terminalis (BNST) is a basal forebrain structure
      involved in many motivational processes closely linked to stress regulation. The
      present study investigated the effect of bilateral lesions of the BNST in male
      Wistar rats on behavioral despair and navigational learning in the Morris water
      maze both of which present stressful challenges. Compared to controls, BNST
      lesioned animals displayed longer duration of immobility in the second of two
      forced swim tests used to assess behavioral despair but performed similarly in
      the water maze task. The present results indicate strongly that the BNST is
      involved in the modulation of behavioral despair. Experimentally induced
      depression by BNST lesions does not impair learning and memory in the water maze
      suggesting a possible dissociation between BNST-mediated depression and cognitive
      performance.

PMID- 16624674
TI  - Superior performance and neural efficiency: the impact of intelligence and
      expertise.
AB  - Superior cognitive performance can be viewed from an intelligence perspective,
      emphasising general properties of the human information processing system (such
      as mental speed and working memory), and from an expertise perspective,
      highlighting the indispensable role of elaborated domain-specific knowledge and
      acquired skills. In exploring its neurophysiological basis, recent research has
      provided considerable evidence of the neural efficiency hypothesis of
      intelligence, indicating lower and more focussed brain activation in brighter
      individuals. The present EEG study investigates the impacts of intelligence and
      expertise on cognitive performance and the accompanying cortical activation
      patterns in the domain of tournament chess. Forty-seven tournament chess players
      of varying intelligence and expertise level worked on tasks drawing on mental
      speed, memory, and reasoning. Half of the tasks were representative for chess,
      while the other half was not. The cortical activation was quantified by means of
      event-related desynchronisation (ERD) in the upper alpha band. Independent
      effects of expertise and intelligence emerged at both, the performance and the
      neurophysiological level. Brighter participants performed better than less
      intelligent ones which was associated with more efficient brain functioning
      (lower ERD) across all tasks. Additionally, a high expertise level was beneficial
      for good task performance but exerted a topographically differentiated influence
      on the cortical activation patterns. The findings suggest that superior cognitive
      performance and the underlying cortical activation are not only a function of
      knowledge and domain-specific competences but also of the general efficiency of
      the information processing system.

PMID- 16624675
TI  - Fear conditioning performance and NMDA receptor subtypes: NR2A differential
      expression in the striatum.
AB  - While considerable evidence implicates NMDA receptors in the hippocampus in
      contextual fear conditioning, the role of other brain regions is less well
      understood. To further investigate this issue, rats were subjected to a
      contextual fear conditioning task and then classified as high or low responders
      according to performance. Density of NMDA receptors was evaluated using [3H]MK
      801 autoradiography in 52 brain areas and expression of NR2A and NR2B subunits
      was studied with in situ hybridization in the same brains. Results revealed no
      differences between high- and low-performance rats in NMDA receptor binding in
      any of the brain areas studied. Similarly, NR2B subunit expression was also not
      different between groups. However, NR2A expression was significantly higher in
      the caudate-putamen of low-performance rats. These results suggest that NMDA
      receptors in the caudate-putamen may also be involved in contextual fear
      conditioning performance.

PMID- 16624676
TI  - Estrogen effects on the expression of Brx in the brain and pituitary of the
      mouse.
AB  - A member of the Dbl family of oncoproteins was discovered in breast cancer tissue
      extracts. This novel protein, designated Brx, contains an estrogen-receptor
      binding motif and is highly expressed in hormone-responsive breast tissue. Due to
      its ability to augment ligand-dependent activation of estrogen receptors, we
      analyzed the expression of Brx in the adult mouse brain and pituitary. Results
      indicated that Brx was expressed in specific regions of the brain and pituitary.
      Furthermore, the results indicate that differences exist in both brain and
      pituitary tissue of male and female mice with greater expression in the female.
      However, estrogen did not influence Brx expression in ovariectomized mice. The
      anatomical studies support a role for Brx in its association with the estrogen
      receptor and that Brx may be involved in neuronal and pituitary function in a
      sexually dimorphic manner.

PMID- 16624677
TI  - Selective extra-dimensional set shifting deficit in a knock-in mouse model of
      Huntington's disease.
AB  - People with early-stage Huntington's disease have been found to have a specific
      deficit in performing an extra-dimensional shift. To date no evidence of this
      deficit has been identified in transgenic or knock-in rodent models of the
      disease. The aim of the present paper then, was to test whether homozygous knock
      in mice derived from the Hdh(CAG(150)) mouse line were impaired in any of five 2
      choice discrimination tasks (simple, compound, compound reversal, intra
      dimensional shift and extra-dimensional shift), and whether these mice were
      impaired at recalling these tasks on the following day. On the extra-dimensional
      shift task the Hdh(CAG(150)) homozygous mice required a greater number of trials
      to reach criteria than mice and the percentage of correct choices within the
      trials was also significantly reduced compared with the animals. For the recall
      tasks, a deficit for recalling the compound reversal test was found in the
      Hdh(CAG(150)) homozygous mice for both number of trials required to reach
      criteria and percentage of correct choices within the trials. Recall for the
      intra-dimensional shift task was also impaired in these animals when measured by
      the percentage of correct choices. Our results demonstrate a pronounced deficit
      in the Hdh(CAG(150)) mice not only on extra-dimensional shift performance in
      agreement with human studies, but also on recall tasks for both the compound
      reversal and the intra-dimensional shift tasks.

PMID- 16624678
TI  - Insulin status differentially affects energy transduction in cerebral
      mitochondria from male and female rats.
AB  - Effects of STZ diabetes and treatment with insulin on cerebral mitochondrial
      metabolism in the male and female rats were examined. Diabetic state resulted in
      generalized decrease in the state 3 respiration rates in the males with
      practically all the substrates except glutamate where the opposite effect was
      seen. Diabetic state had no adverse effect on the respiratory activity in the
      females. Insulin treatment had no restorative effect in the males. By contrast in
      the females, adverse effects were noted. The cytochromes contents decreased in
      STZ diabetes with the effect being more pronounced in the males; treatment with 1
      unit of insulin restored the cytochromes contents. STZ diabetes also resulted in
      decreased dehydrogenases activities with the effect being more pronounced in the
      females: insulin treatment resulted in hyper-stimulation of glutamate
      dehydrogenase and succinate DCIP reductase activities; restoration of malate
      dehydrogenase activity was only partial. The results point out that STZ diabetes
      and insulin treatments differentially affect cerebral mitochondrial energy
      metabolism in the male and female rats.

PMID- 16624679
TI  - Neurodegeneration induced by complex I inhibition in a cellular model of familial
      amyotrophic lateral sclerosis.
AB  - G93A Cu/Zn superoxide dismutase (SOD1), a human mutant SOD1 associated with
      familial amyotrophic lateral sclerosis, increased the toxicity of the
      mitochondrial toxin rotenone in the NSC-34 motoneuronal cell line. G93ASOD1 cells
      died more than untransfected and wild-type SOD1 cells after 6 and 24h exposure to
      12.5 microM rotenone. Biparametric flow cytometry showed that rotenone induced
      rapid hyperpolarization of mitochondrial membrane potential (deltapsi(m)) in all
      the cell lines, followed by depolarization, and then by cell death. However,
      G93ASOD1 mitochondria were significantly more likely to shift from a
      hyperpolarized to a depolarized condition, and within the still viable cell
      population there was a higher proportion with depolarized mitochondria, a
      condition that can be envisaged as a commitment to cell death. ATP, which is
      needed to prevent loss of deltapsi(m), decreased more rapidly and to a greater
      extent in rotenone-treated G93ASOD1 cells than in the untransfected and
      wtSOD1cells. In all the cell lines, 1h after rotenone exposure, mitochondrial
      hyperpolarization was accompanied by the formation of a comparable amount of
      reactive oxygen species. However, G93ASOD1 cells reached the highest reactive
      oxygen species level since their basal level was higher than in untransfected and
      wild-type SOD1 cells. Our findings indicate that the mutant protein G93ASOD1
      enhances the vulnerability of motor neurons to rotenone by mechanism(s) involving
      oxidative stress and perturbed mitochondrial homeostasis. This suggests that
      motor neurons from individuals carrying the mutant G93ASOD1 are at greater risk
      of death after inhibition of the electron transport chain.

PMID- 16624681
TI  - Pharmacokinetic and pharmacodynamic characteristics of beta-blockers: when
      differences may matter.

PMID- 16624680
TI  - Sustained restoration of autonomic balance with long- but not short-acting
      metoprolol in patients with heart failure.
AB  - BACKGROUND: The purpose of this study was to compare the effects of immediate
      release (IR) metoprolol and extended-release (XL) metoprolol on measures of heart
      rate variability in chronic systolic heart failure patients. METHODS AND RESULTS:
      Thirteen metoprolol-treated heart failure patients were randomized to a 2-way
      crossover study of equal daily doses of metoprolol IR and metoprolol XL, each
      administered for 3 weeks. After each 3-week interval, patients underwent 24-hour
      Holter and ambulatory blood pressure monitoring. Over the entire 24-hour period,
      the ratio of high to total variability (normalized measure of parasympathetic
      activity) was significantly greater (P < .05), the ratio of low to total
      variability (normalized measure of sympathetic activity) was significantly lower
      (P < .05), and the ratio of high to low variability (index of parasympathetic to
      sympathetic balance) was greater (P < .08) for metoprolol XL compared with
      metoprolol IR. Over the entire 24-hour period, both systolic and diastolic blood
      pressure were significantly lower for metoprolol XL compared with metoprolol IR
      (P < .0001, and .0005, respectively). CONCLUSION: These data suggest that with
      twice daily dosing, metoprolol IR is inferior to metoprolol XL in its effects on
      heart rate variability, autonomic balance, and blood pressure in patients with
      heart failure.

PMID- 16624682
TI  - Predictors of remodeling in the CRT era: influence of mitral regurgitation, BNP,
      and gender.
AB  - BACKGROUND: We analyzed quantitative echocardiographic data from a large heart
      failure cohort receiving medical and cardiac resynchronization therapy (CRT) to
      determine baseline predictors of progressive left ventricular (LV) enlargement.
      METHODS AND RESULTS: Quantitative echocardiograms were obtained at baseline and
      after 6 months in 776 outpatients with chronic heart failure who participated in
      MIRACLE (Multicenter InSync Randomized Clinical Evaluation) and MIRACLE-ICD
      (Multicenter InSync ICD Randomized Clinical Evaluation). We used multivariable
      regression to determine clinical, therapeutic, and echocardiographic
      characteristics that predicted a subsequent change in left ventricular end
      diastolic volume (LVEDV). Over 6 months, LVEDV increased in 308 (40%) and
      decreased in 468 (60%) patients. Baseline mitral regurgitation and levels of
      plasma brain natriuretic peptide (BNP) independently predicted LV enlargement,
      whereas CRT predicted a decrease in LVEDV (all P < .01). In all models tested,
      male gender was an independent risk factor for progressive LV enlargement (P <
      .0001). CONCLUSION: Men show more prominent LV dilation than women in chronic
      heart failure despite medical and device therapy. Rates of LV remodeling are
      influenced further by mitral regurgitation, plasma BNP, and CRT. Future studies
      should take these clinical factors into account when determining the influence of
      genetic factors and novel therapies on ventricular remodeling in chronic heart
      failure.

PMID- 16624683
TI  - Left ventricular reconstruction brings benefit for patients with ischemic
      cardiomyopathy.
AB  - BACKGROUND: Optimal treatment strategies for some patients with ischemic
      cardiomyopathy can be unclear. We compared the outcome for patients treated with
      revascularization only or with additional ventricular reconstruction. METHODS AND
      RESULTS: We compared 74 consecutive patients with an ejection fraction <35% and a
      left end-systolic volume index >80 mL/m(2). All patients underwent
      revasularization but some received only revascularization (group 1) and some were
      randomized into a group that received additional ventricular reconstruction
      (group 2). Preoperative and postoperative ejection fraction, end-systolic volume,
      mitral regurgitation, mortality, heart failure (HF) symptoms, and recurrence were
      compared between groups. There was 1 postoperative death in group 2 (P =. 58).
      Preoperative ejection fraction between the groups was similar (P =. 19) but it
      differed significantly postoperatively (P < .001). HF class (New York Heart
      Association) decreased more in group 2 (group 2, 2.3 +/- 0.4 versus group 1, 1.4
      +/- 0.4; P < .001). Incidence of HF recurrence and rehospitalization was
      significantly less in group 2 (P = .028). The postoperative development of higher
      grade mitral regurgitation was greater in group 1 (147 +/- 32 mL/m(2) versus 119
      +/- 25 mL/m(2), P = .024). CONCLUSION: The outcome at midterm of coronary artery
      surgery alone in patients with a preoperative large left ventricle was inferior
      compared with the outcome achieved with additional ventricular restoration.

PMID- 16624684
TI  - The treatment of ischemic heart failure with surgical ventricular restoration
      (SVR): new evidence of benefit.

PMID- 16624685
TI  - Biventricular pacemaker upgrade in previously paced heart failure patients-
      improvements in ventricular dyssynchrony.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) reduces symptoms and
      mortality in patients with left bundle branch block (LBBB) and severe chronic
      heart failure. There are few data demonstrating the effects of CRT on
      contemporary dyssynchrony variables in patients with advanced heart failure who
      have been chronically paced from the right ventricle (RV). METHODS AND RESULTS:
      We reviewed baseline and follow-up clinical and echocardiographic data on
      patients receiving CRT in a single centre. Indices of global left ventricular
      (LV) function and dyssynchrony before and after CRT were measured. Patients were
      then divided into those receiving their first device (n = 39) and those receiving
      CRT as an upgrade to existing RV pacemakers (n = 32). Baseline demographic
      variables, indices of global LV function, symptomatic status, renal function,
      hemodynamics, and diuretic requirements were not different between previously
      paced patients and nonpaced patients. Mean length of RV pacing in the previously
      paced patients was 59 months (range 12-167 months). Patients in the previously
      paced group had a broader QRS complex than patients with intrinsic LBBB.
      Aortopulmonary delay of longer than 40 ms was present in 68% of all subjects, 67%
      had intraventricular septal and posterior wall motion delay longer than 130 ms,
      and 59% had an intraventricular delay as measured by tissue Doppler imaging of
      longer than 65 ms. There was no difference between paced and nonpaced patients
      for any of these measures of dyssynchrony. QRS duration was reduced to a greater
      extent in the previously paced patients than those with no previous device
      therapy. CRT led to important reductions in each dyssynchrony variable in both
      patients with previous RV pacing and those with intrinsic LBBB. The magnitude of
      these changes in measures of dyssynchrony was not different between the 2 groups.
      In all patients undergoing CRT, 50% had a reduction in furosemide dose at 3
      months, 56% an improvement of at least 1 grade in New York Heart Association
      status, and 66% an improvement of at least 5% in LVEF. Divided by group,
      previously paced patients were no more or less likely than newly implanted
      patients to achieve one or more of these clinical outcomes. CONCLUSION: Our data
      suggest that patients with RV pacing and heart failure have similar dyssynchrony
      as patients with intrinsic LBBB. CRT leads to improvements in LV global function,
      dyssynchrony variables and symptoms in patients chronically paced from the RV
      that are similar to those observed in patients with LBBB without preexisting
      devices.

PMID- 16624686
TI  - Appropriateness of spironolactone prescribing in heart failure patients: a
      population-based study.
AB  - BACKGROUND: The Randomized Aldactone Evaluation Study (RALES) established the
      safety and benefit of spironolactone for heart failure (HF) patients with
      systolic dysfunction. However, recent data have raised concerns regarding
      hyperkalemia secondary to spironolactone use and suggest it occurs more commonly
      in routine practice. METHODS AND RESULTS: We explored factors potentially
      associated with hyperkalemia from spironolactone therapy in a population-based
      cohort of 9165 HF patients hospitalized in Ontario, Canada, between 1999 and
      2001. Compared with patients enrolled in RALES, community-based patients were
      older (mean age 75 years versus 65 years, P < .001) and were more likely to be
      female (50% versus 27%, P < .001). Of the 1502 patients that were prescribed
      spironolactone at discharge, 18% had elevated serum potassium levels (>5 mmol/L)
      during hospitalization and 23% were discharged on concurrent potassium
      supplements. Although only 8% of patients had serum creatinine >2.5 mg/dL, many
      patients had stage III (53.1%), stage IV (12.8%), or stage V (3.9%) chronic renal
      insufficiency according to glomerular filtration rate. CONCLUSION: Spironolactone
      was often prescribed to inappropriate HF candidates because of the presence of
      relative or absolute contraindications. These findings highlight the need for
      more careful patient selection when prescribing spironolactone to minimize
      potential life-threatening hyperkalemia.

PMID- 16624687
TI  - Randomized controlled trial of telephone case management in Hispanics of Mexican
      origin with heart failure.
AB  - BACKGROUND: Disease management is effective in the general population, but it has
      not been tested prospectively in a sample of solely Hispanics with heart failure
      (HF). We tested the effectiveness of telephone case management in decreasing
      hospitalizations and improving health-related quality of life (HRQL) and
      depression in Hispanics of Mexican origin with HF. METHODS AND RESULTS:
      Hospitalized Hispanics with chronic HF (n = 134) were enrolled and randomized to
      intervention (n = 69) or usual care (n = 65). The sample was elderly (72 +/- 11
      years), New York Heart Association class III/IV (81.3%), and poorly educated
      (78.4% less than high school education). Most (55%) were unacculturated into US
      society. Bilingual/bicultural Mexican-American registered nurses provided 6
      months of standardized telephone case management. Data on hospitalizations were
      collected from automated systems at 1, 3, and 6 months after the index hospital
      discharge. Health-related quality of life and depression were measured by self
      report at enrollment, 3, and 6 months. Intention to treat analysis was used. No
      significant group differences were found in HF hospitalizations, the primary
      outcome variable (usual care: 0.49 +/- 0.81 [CI 0.25-0.73]; intervention: 0.55 +/
      1.1 [CI 0.32-0.78] at 6 months). No significant group differences were found in
      HF readmission rate, HF days in the hospital, HF cost of care, all-cause
      hospitalizations or cost, mortality, HRQL, or depression. CONCLUSION: These
      results have important implications because of the current widespread enthusiasm
      for disease management. Although disease management is effective in the
      mainstream HF patient population, in Hispanics this ill, elderly, and poorly
      educated, a different approach may be needed.

PMID- 16624688
TI  - Caffeine prolongs exercise duration in heart failure.
AB  - BACKGROUND: Caffeine increases submaximal exercise performance in healthy young
      subjects; its effects on exercise tolerance in heart failure (HF) have not been
      characterized. METHODS AND RESULTS: To determine whether caffeine increases
      exercise tolerance in HF, caffeine (4 mg/kg intravenously, equivalent to 2 cups
      of coffee) or vehicle were infused into 10 treated HF patients (left ventricular
      ejection fraction 25 +/- 2 %), and 10 age-matched normal subjects (N) on 2
      separate days in a double-blind, randomized, crossover design. We measured heart
      rate, blood pressure, and ventilation at rest and during graded cycling (15
      W/minute) to peak effort. Peak oxygen consumption was unaffected in either group.
      Mean exercise time was unchanged in N (1,013 +/- 87 versus 988 +/- 107 seconds; P
      = .86) but was significantly increased by caffeine in HF (from 511 +/- 28 to 560
      +/- 37 seconds; P = .004) despite an increase in peak minute ventilation (P <
      .05). Resting and peak blood pressures were higher after caffeine (P < .05) in
      HF, not N. CONCLUSION: Caffeine allows HF patients to exercise longer at peak
      effort.

PMID- 16624689
TI  - LVAD-induced reverse remodeling: basic and clinical implications for myocardial
      recovery.
AB  - BACKGROUND: With improved technology, increasing clinical experience, and
      expanding indications for use, left ventricular assist devices (LVADs) are
      assuming a greater role in the care of patients with end-stage heart failure.
      Early in the course of LVAD use as a bridge to transplant, it became evident that
      some patients exhibit substantial recovery of ventricular function, which led to
      the concept of reverse remodeling. METHODS AND RESULTS: Herein we summarize and
      integrate insights derived from a multitude of studies that have investigated how
      LVAD support influences ventricular structural, cellular, extracellular matrix,
      molecular, biochemical, and metabolic characteristics of the end-stage failing
      heart. The focus includes a review of the extent and sustainability of reverse
      remodeling, the important advances in understanding of the pathophysiology of
      heart failure derived from these studies and the implications of these findings
      for development of new therapeutic strategies. CONCLUSION: In brief, studies of
      LVAD-heart interactions have led to the understanding that although we once
      considered the end-stage failing heart of patients near death to be irreversibly
      diseased, when given sufficient mechanical unloading and restoration of more
      normal neurohormonal milieu, a relatively large degree of myocardial recovery is
      possible. Comparison of effects on right and left ventricles have provided
      mechanistic insights by implicating hemodynamic unloading as primarily regulating
      certain aspects of reverse remodeling, neurohormonal factors as regulating other
      aspects, and joint regulation of still other aspects. As such these observations
      have driven a shift of thinking of chronic heart failure as a progressive
      irreversible disease process to a potentially treatable entity.

PMID- 16624690
TI  - Aldosterone antagonism improves endothelial-dependent vasorelaxation in heart
      failure via upregulation of endothelial nitric oxide synthase production.
AB  - BACKGROUND: Altering the renin-angiotensin aldosterone system improve mortality
      in heart failure (HF) in part through an improvement in nitric oxide (NO)
      mediated endothelial function. This study examined if spironolactone affects
      endothelial nitric oxide synthase (eNOS) and NO-mediated vasorelaxation in HF.
      METHODS AND RESULTS: Rats with HF after coronary artery ligation were treated
      with spironolactone for 4 weeks. Rats with HF had a decrease (P < .05) in left
      ventricular (LV) systolic pressure (130 +/- 7 versus 118 +/- 6 mm Hg) and LV
      pressure with respect to time (9,122 +/- 876 versus 4,500 +/- 1971 mm Hg/second)
      with an increase in LV end-diastolic pressure (4 +/- 2 versus 23 +/- 8 mm Hg).
      Spironolactone did not affect hemodynamics but it improved (P < .05) endothelial
      dependent vasorelaxation at more than 10(-8) M acetylcholine that was abolished
      with N(G)-monomethyl-L-arginine. The eNOS levels were decreased (P < .05) in the
      LV and the aorta; spironolactone restored LV and aortic eNOs levels to normal.
      CONCLUSION: Spironolactone prevents the decrease in eNOS in the LV and aorta and
      improves NO-dependent vasorelaxation, suggesting that one potential mechanism of
      spironolactone is an improvement in vasoreactivity mediated though an increase in
      NO.

PMID- 16624692
TI  - Intergenerational transfer of douching information.
AB  - STUDY OBJECTIVE: To characterize the discussions on douching that female
      parents/guardians have with daughters. DESIGN: A questionnaire assessing personal
      douching history, beliefs on the practice of douching, and what they had
      discussed or intended to discuss about douching with their daughters was
      administered to women who were parenting females 11-21 years of age.
      PARTICIPANTS: Fifty-seven women who had douched or currently douche completed the
      questionnaire. RESULTS: Fifty-six of the women had discussed or planned to
      discuss the subject with their daughters. The girls with whom they had had a
      discussion were significantly older (16.2 years) than those with whom they
      planned to have a discussion (14.1 years). Most (73%) of the women had encouraged
      or planned to encourage douching, while only 18% had or planned to discourage it.
      Mothers had or planned to have the conversation in the context of menses (76%),
      sexual activity (40%), or when their daughter instigated the conversation (44%).
      Over 40% of the mothers had not or did not intend to discuss any negatives about
      douching. Only ten of the women stated that a health care provider had spoken to
      them or their daughter about the subject. CONCLUSION: Female parents/guardians
      are an important source of information about douching for their daughters. Health
      care providers need to educate girls as well as the women who parent them on the
      health risks associated with douching. Public campaigns aimed at decreasing
      douching should target this intergenerational transfer of information.

PMID- 16624694
TI  - Assessment of knowledge and attitudes of young uninsured women toward human
      papillomavirus vaccination and clinical trials.
AB  - STUDY OBJECTIVE: To assess knowledge and attitudes of young uninsured women
      toward human papillomavirus (HPV) vaccination and clinical trials. DESIGN: Cross
      sectional study. SETTING: Clinic-based sample in Brazil. PARTICIPANTS: A
      consecutive sample of 204 women aged 16 to 23 years, attending a public
      outpatient gynecological clinic. INTERVENTIONS: A questionnaire administered by
      in-person interview. MAIN OUTCOME MEASURES: Data on knowledge and attitudes
      towards HPV vaccination. RESULTS: Overall, 72% of the respondents would enroll in
      a HPV vaccine trial, despite the fact that 69% of women were ignorant of what HPV
      may cause, and only 10% acknowledged that HPV might lead to cervical cancer. The
      need of a placebo arm (31%) and three vaccinations injections (26%) were the
      trial design characteristics most cited for deterring participation. Factors
      promoting participation were "careful/detailed consultations by the same
      physician" (92%), "access to more information on women's health" (84%), and
      "office visits on time" (79%); whereas "clinic too far from home" (36%), "fear of
      adverse events" (29%), and "gynecologic examination discomfort" (25%) were the
      most commonly reported reasons for not enrolling in a trial. Being sexually
      active, more than three lifetime sexual partners and perception of high risk for
      cervical cancer were predictors of participation in a HPV vaccine trial.
      CONCLUSIONS: Knowledge of HPV infection and cervical cancer is low in this urban,
      young population. Thus, when planning HPV vaccine trials, it is important to
      consider implementing educational programs to provide knowledge of the benefits
      of a preventive vaccine and information on the etiology of and risk factors for
      cervical cancer.

PMID- 16624695
TI  - The manchester-fothergill procedure as a fertility sparing alternative for pelvic
      organ prolapse in young women.
AB  - Although reproductive organ prolapse typically affects older, parous women, a
      certain population of children and adolescents, primarily adolescents with
      congenital spinal defects, are also at risk. The Manchester-Fothergill procedure
      was first performed in 1888 by Dr. Archibald Donald of Manchester, England.
      Although this is a well-described procedure in historic texts, the practical
      application is not often employed, and modern surgical texts rarely describe how
      to perform this surgery. It is crucial to educate younger physicians about the
      technical aspects of this procedure so as not to lose this operation as an
      alternative surgical approach. We present a case of recurrent uterine prolapse
      after a prior laparoscopic uterine suspension procedure. In order to address
      recurrent prolapse, which was accompanied by cervical elongation, this young
      woman elected to have additional surgical management with the Manchester
      Fothergill procedure. We describe the procedure in detail, accompanied by
      photographs taken during the operation to fully illustrate the extent of this
      patient's condition and to document the surgical technique. The Manchester
      Fothergill procedure is an additional fertility-sparing surgical approach to
      treatment of pelvic organ prolapse.

PMID- 16624696
TI  - Microperforate hymen resulting in pelvic abscess.

PMID- 16624697
TI  - Congenital imperforate hymen and its life-threatening consequences in the
      neonatal period.
AB  - Imperforate hymen is most commonly an isolated finding and usually remains
      asymptomatic until puberty. Rarely, symptoms of imperforate hymen manifest
      antenatally as well as in the neonatal period, requiring surgical correction for
      life-threatening consequences. We report a 5-day-old infant with a large
      hydrometrocolpos causing severe renal compromise and abdominal ascites,
      successfully surgically treated in the neonatal period. Associated polydactyly
      suggested McKusick-Kaufman syndrome.

PMID- 16624698
TI  - Labial edema following treatment of condyloma acuminata with CO(2) laser in an
      adolescent: a case report and literature review.
AB  - PURPOSE: To describe a case of bilateral labial edema in an adolescent patient
      and review the literature on this rare occurrence. MATERIAL: A 16-year-old girl
      was treated for widespread genital condyloma acuminata with CO(2) laser under
      general anesthesia and local lidocaine injections. Severe bilateral labial edema
      occurred after 48 hours. RESULTS: Lidocaine and Latex dermal patch tests for
      delayed hypersensitivity were negative. The edema resolved following treatment
      with local ice packs and magnesium sulfate compresses for 2 weeks. CONCLUSION:
      This is the first description of severe bilateral labial edema after CO(2) laser
      treatment for condyloma acuminata. We suggest that transient local lymphatic
      obstruction was the reason for this complication. The literature on this rare
      occurrence is reviewed.

PMID- 16624699
TI  - Special needs call for specialized services: a response to no need to specialize:
      reproductive health is for all adolescents.

PMID- 16624700
TI  - Reproductive care for adolescents with disability: where should they get it?

PMID- 16624701
TI  - No need to specialize: reproductive health is for all adolescents.

PMID- 16624702
TI  - Pubic hair removal -- pearls and pitfalls.

PMID- 16624703
TI  - A case of autoimmune progesterone dermatitis in an adolescent female.
AB  - BACKGROUND: Progesterone-induced dermatitis is a rare disorder. It typically
      occurs in females due to an autoimmune phenomenon to endogenous progesterone
      production, but can also be caused by exogenous intake of a synthetic progestin.
      Here, we present a case of autoimmune progesterone dermatitis (AIPD) seen in an
      adolescent female. CASE: The patient is a 15-year-old Caucasian female with no
      significant past medical history and no prior exogenous hormone use, who
      presented to her primary care physician complaining of cyclic skin eruptions. She
      noted that her dermatologic symptoms occurred monthly, just prior to her menses.
      An intradermal skin test using 0.1 cc of progesterone was performed. The patient
      immediately developed a wheal, confirming the diagnosis of AIPD. The patient was
      begun on a continuous regimen of an oral contraceptive pill with 30 micrograms of
      ethinyl estradiol and 0.15 mg of levonorgestrel. The skin eruptions have not
      returned since the initiation of this therapy. CONCLUSION: Autoimmune
      progesterone dermatitis manifests via the occurrence of cyclic skin eruptions.
      Women with the disorder commonly present with dermatologic lesions in the luteal
      phase of the menstrual cycle. Diagnosis of AIPD is confirmed by performing a skin
      allergen test using progesterone. Due to its rarity, AIPD should be considered a
      diagnosis of exclusion. In cases believed to be due to an endogenous production
      of progesterone, several methods of therapy have been attempted. The ultimate
      goal of therapy is the suppression of ovulation, which will prevent endogenous
      hormone production as progesterone is only produced in ovulatory cycles.
      Currently, the first-line choice of therapy is a combination oral contraceptive.
      If this treatment is ineffective, patients have been treated with danazol,
      gonadotropin releasing hormone analogs, tamoxifen, and oophorectomy with varying
      success.

PMID- 16624704
TI  - The breastfeeding teen.

PMID- 16624705
TI  - Diagnostic ultrasonography in animals -- continuation of the clinical
      examination?

PMID- 16624706
TI  - Biofilms: a role in recurrent mastitis infections?
AB  - Mastitis remains one the most important diseases in dairy cattle despite the
      progress made in improving general udder health in recent years. Epidemiological
      studies have revealed that following treatment with antimicrobials,
      bacteriological cure rates vary between 0% and 80% but with no evidence of a
      significant loss of activity of the major classes of antibiotics licensed for the
      treatment of bovine mastitis. Recurrent infections are often attributable to
      biofilm growth of bacteria and this review provides an overview of those
      mechanisms related to bacterial biofilm growth in mastitis. Biofilm formation is
      accompanied by significant genetic and subsequent physiological changes in the
      microorganisms resulting, inter alia, in a loss of sensitivity to virtually all
      classes of antibiotics.

PMID- 16624707
TI  - Current understanding of the aetiology and laboratory diagnosis of footrot.
AB  - Footrot is a highly contagious disease of the feet of ruminants caused by the
      synergistic action of certain bacterial species of which Dichelobacter nodosus
      (D. nodosus) is the main transmitting agent. The infection is specific to sheep
      and goats, although it has also been reported in cattle, horses, pigs, deer and
      mouflon. The antigenic diversity of D. nodosus is due to variations in the DNA
      sequence of its fimbrial subunit gene (fimA) and provides the basis for
      classification of the organism into at least 10 major serogroups (A-I and M), the
      distribution of which varies with different geographical locations. Host immune
      response to vaccination is serogroup specific. There are three different clinical
      forms of disease caused by virulent, intermediate and benign strains of D.
      nodosus, respectively. In order to facilitate rapid and reliable clinical
      diagnosis, virulence determination, strain differentiation and serogroup
      identification for effective control measures, immunological tests, DNA probes
      and PCR based techniques have been introduced. This review summarises the current
      understanding of the mechanisms of antigenic diversity of D. nodosus as well as
      advances made in its strain differentiation and diagnosis.

PMID- 16624708
TI  - The anti-inflammatory effects of IV administered clenbuterol in horses with
      recurrent airway obstruction.
AB  - Cyclic AMP elevating agents have been shown to exhibit anti-inflammatory
      properties in addition to functions such as bronchodilation. The aim of this
      study was to investigate this dual action of clenbuterol (CB; Ventipulmin) on
      horses affected with recurrent airway obstruction (RAO). Seven RAO susceptible
      horses received inhalation challenges with aerosolised lipopolysaccharide (LPS),
      hay dust suspension (HDS) and Aspergillus fumigatus antigen (AF) with and without
      prior treatment with intravenous CB. Data showed that CB exerted significant
      beneficial effects on lung function, total cell count (TCC) and bronchoalveolar
      lavage neutrophil influx. In addition, CB significantly decreased the expression
      of several pro-inflammatory cytokines and chemokines in the alveolar macrophages
      of RAO-susceptible horses after challenge with LPS and HDS, and increased the
      expression of interleukin-6, known to act as a pro-and anti-inflammatory
      cytokine, following different challenges. This anti-inflammatory activity of CB
      is of additive value to its currently recognised use in equine RAO.

PMID- 16624709
TI  - Analysis of clinical signs associated with bovine spongiform encephalopathy in
      casualty slaughter cattle.
AB  - Clinical signs associated with bovine spongiform encephalopathy (BSE) were
      studied in 1008 casualty slaughter cattle over 30 months of age to compare the
      results with the BSE status as determined by postmortem tests. The clinical BSE
      status was assessed using seven different criteria based on various publications.
      Only one (0.10%) out of 997 casualty slaughter cattle with a matching postmortem
      test result was positive for BSE. The BSE case was identified by only two case
      definitions tailored specifically to recumbent cases. The variety and often
      equivocal definition of clinical signs associated with BSE is reflected by the
      difference in the criteria that usually identified different animals as BSE
      suspects. The BSE status may be more difficult to assess in recumbent animals
      that do not allow a full clinical examination, and BSE may not be suspected if
      another disease is present that may mask signs of BSE.

PMID- 16624710
TI  - The effects of transplacental porcine circovirus type 2 infection on porcine
      epidemic diarrhoea virus-induced enteritis in preweaning piglets.
AB  - The effects of transplacental porcine circovirus type 2 (PCV2) infection on
      porcine epidemic diarrhoea virus (PEDV)-induced enteritis were examined in
      neonatal piglets. Six pregnant sows were randomly allocated to an infected (n=3)
      or control group (n=3). Three pregnant sows were inoculated intranasally with 6
      mL of tissue culture fluid containing 1.2 x 10(5) tissue culture infective doses
      50% (TCID(50))/mL of PCV2 strain SNUVR000470 three weeks before the expected
      farrowing date. Three control pregnant sows were similarly exposed to uninfected
      cell culture supernatants. Thirty piglets from PCV2-infected sows were randomly
      assigned to two groups (A and B) of 15 piglets each. Another 30 piglets from
      noninfected sows were randomly assigned to two groups (C and D) of 15 piglets
      each. The piglets in groups A and C were dosed orally at three days of age with
      2mL of virus stock (1 x 10(6.5) TCID(50)/mL) of the PEDV strain, SNUVR971496, at
      the third passage. The mean villous height and crypt depth (VH:CD) ratio in PEDV
      infected piglets from PCV2-infected sows (group A) were significantly different
      from those of the PEDV-infected piglets from PCV2 negative sows (group C) at 36,
      48, and 72 h post-inoculation (hpi) (P<0.05). In PEDV-infected piglets from PCV2
      infected sows (group A), significantly more PEDV nucleic acid was detected in the
      jejunal tissues (P<0.05) at 24 hpi than in the same tissues of the PEDV-infected
      piglets from PCV2 negative sows (group C). Thereafter, at 36, 48, 60, and 70 hpi
      significantly more PEDV nucleic acid (P<0.05) was detected in the jejunal tissues
      of the PEDV-infected piglets from PCV2 negative sows (group C) than those of the
      PEDV-infected piglets from the PCV2-infected sows (group A). It is concluded that
      the clinical course of PEDV disease was markedly affected by transplacental
      infection of PCV2.

PMID- 16624711
TI  - Characterisation of transthyretin and retinol-binding protein in plasma and
      cerebrospinal fluid of dogs.
AB  - The aim of this study was to investigate differences in concentrations of vitamin
      A, transthyretin (TTR) and retinol-binding protein (RBP) between plasma and
      cerebrospinal fluid (CSF) in dogs. RBP was detected using ELISA, and both RBP and
      TTR by Western blot analysis after separation on SDS-PAGE. Vitamin A was
      determined by high performance liquid chromatography. RBP and TTR as well as
      vitamin A were detected in all samples but at substantially lower concentrations
      in CSF compared to plasma. RBP in dog plasma showed a similar molecular mass to
      that of humans, whereas canine TTR had a lower molecular mass. Comparison between
      plasma and CSF showed that both RBP and TTR were of lower molecular mass in CSF.
      In CSF, RBP and retinol were present at 10-100-fold lower concentrations compared
      to plasma. Retinyl esters were present only in minute amounts in 5/17 samples. In
      conclusion, the CSF of dogs compared to humans is significantly different in
      terms of both quality and quantity of transport proteins for vitamin A.

PMID- 16624712
TI  - Monocarboxylate transporter 1 gene expression in the ovine gastrointestinal
      tract.
AB  - In this study, we investigated the tissue distribution and expression of
      monocarboxylate transporter 1 (MCT1) along the gastrointestinal tract of sheep.
      Western blot analysis suggested the presence of MCT1 as a 43-kDa protein in
      immunoblots of membranes from the various tissues examined. The results of
      Western blotting were further confirmed by immunohistochemical studies, which
      revealed intense immunoreactivity for the MCT1 protein in the forestomach (rumen,
      reticulum and omasum) and large intestine (caecum, proximal and distal colon).
      Moderate reactivity, however, was detected in the abomasum, while no
      immunoreactivity could be seen in any regions of the small intestine examined.
      Furthermore, MCT1 was expressed at the mRNA level as determined by reverse
      transcriptase polymerase chain reaction (RT-PCR), which showed a band of the
      expected size (300 bp) in all tissues examined. From these results we concluded
      that MCT1 protein is highly expressed and distributed in the stomach and large
      intestine of sheep suggesting that MCT1 may play a significant role in the
      transport of short chain fatty acids and their metabolites in the
      gastrointestinal tract of ruminants.

PMID- 16624713
TI  - Ingestion of starch-rich meals after exercise increases glucose kinetics but
      fails to enhance muscle glycogen replenishment in horses.
AB  - Fatiguing exercise substantially decreases muscle glycogen concentration in
      horses, impairing athletic performance in subsequent exercise bouts. Our
      objective was to determine the effect of ingestion of starch-rich meals after
      exercise on whole body glucose kinetics and muscle glycogen replenishment. In a
      randomized, cross-over study seven horses with exercise-induced muscle glycogen
      depletion were either not fed for 8 h, fed half of the daily energy requirements
      ( approximately 15 Mcal DE) as hay, or fed an isocaloric amount of corn 15 min
      and 4 h after exercise. Starch-rich meals fed after exercise, when compared to
      feed withholding, resulted in mild to moderate hyperglycemia (5.7+/-0.3 vs. 4.7+/
      0.3 mM, P<0.01) and hyperinsulinemia (79.9+/-9.3 vs. 39.0+/-1.9 pM, P<0.001), 3
      fold greater whole body glucose kinetics (15.5+/-1.4 vs. 5.3+/-0.4 micromol kg(
      1)min(-1), P<0.05), but these only minimally enhanced muscle glycogen
      replenishment (171+/-19 vs. 170+/-56 and 260+/-45 vs. 294+/-29 mmol/kg dry weight
      immediately and 24 h after exercise, P>0.05). It is concluded that after
      substantial exercise-induced muscle glycogen depletion, feeding status only
      minimally affects net muscle glycogen concentrations after exercise, despite
      marked differences in soluble carbohydrate ingestion and availability of glucose
      to skeletal muscle.

PMID- 16624714
TI  - The feeding of ad libitum dietary protein to organic growing-finishing pigs.
AB  - The effects of three dietary protein levels on growth, meat, and carcass traits
      were studied in organic pigs fed a three-phase diet. Assuming lysine was the
      first limiting amino acid, feeds were formulated to ileal digestible (ID) lysine
      content, with the ID lysine:crude protein ratio set at a constant of 4%. Feeds
      were also formulated to an isocaloric rate (net energy: 9.4 MJ/kg during the
      first feeding phase, 9.25 MJ/kg during the second feeding phase and 9.1 MJ/kg
      during the finisher phase), with a high (HP), a medium (MP) or a low (LP) protein
      content ranging from 20% to 14% crude protein (CP). ID lysine content of the LP
      and MP feed was, respectively, 80% and 90% of the ID lysine content of the HP
      feed. The nutrient formulation of the HP feed was similar to nutrient levels
      commonly used in conventional Belgian pig farming. From 20 to 40 kg liveweight,
      the pigs showed better feed conversion ratios, with an increasing dietary protein
      concentration (r(2)=0.84). This effect was not observed in the second and third
      phases, although a significant effect of protein concentration on voluntary feed
      intake in the second phase did occur (P=0.018), probably as a compensation for
      the lower protein concentration in the LP diet. Analysis of the carcasses showed
      a lower meat percentage with lower protein concentration (P<0.05), whereas
      influences on meat quality were limited. It was concluded that whereas during the
      first phase of growth, higher protein concentration leads to better performance,
      from the second phase onwards (45 kg), at least with isocaloric diets, a decrease
      in protein content (corresponding to a 10% reduction in dietary ID lysine levels
      compared to conventional pig fattening) may be used in organic growing-finishing
      pig nutrition.

PMID- 16624715
TI  - The effects of free fat graft or cellulose membrane implants on laminectomy
      membrane formation in dogs.
AB  - The purpose of this study was to determine the effect of cellulose membrane or
      free fat grafts (FFG) on laminectomy membrane (LM) formation. Eighteen dogs were
      randomly divided into three groups of six dogs. All dogs underwent a modified
      dorsal laminectomy on T(13)-L(1). The laminectomy defect was left uncovered in
      the control group but either a FFG or a cellulose membrane implant was provided
      in the other two groups. The dogs were evaluated through neurological
      examination, myelography, macroscopic roundness index of spinal cord and
      histological evaluations of epidural fibrosis and spinal cord. The results showed
      a significant difference between the control and the FFG group, with the FFG
      causing neurological deficits and spinal cord compression as assessed by the
      roundness index of the spinal cord. Both FFG and cellulose membrane were
      partially effective in preventing LM formation. The use of FFG was associated
      with a high rate of significant neurological complications and spinal cord
      lesions.

PMID- 16624716
TI  - Effects of time of progesterone supplementation on embryo development and
      interferon-tau production in the cow.
AB  - We have investigated the effects of the timing of progesterone supplementation on
      early embryo development in mature, non-lactating Holstein-Friesian cows. Animals
      were inseminated 72 h (day 1) and 96 h following prostaglandin injection and were
      either left as untreated controls (n=6) or received progesterone supplementation
      from either days 5 to 9 (early; n=6) or from days 12 to 16 (late; n=6). Daily
      plasma samples were collected until day 16, when cows were slaughtered and
      reproductive tracts recovered and flushed to collect embryos and to measure
      interferon-tau activity. Both early and later progesterone supplementation
      resulted in marked increases in plasma progesterone (P<0.01). Early, but not
      late, progesterone supplementation resulted in a fourfold increase in trophoblast
      length (P<0.01) and a sixfold increase in uterine concentration of interferon-tau
      (P<0.05). The results demonstrate that progesterone supplementation during the
      postovulatory rise, but not later in the luteal phase, increases embryo
      development and interferon-tau production.

PMID- 16624717
TI  - Obstruction of equine small intestine associated with focal idiopathic
      eosinophilic enteritis: an emerging disease?
AB  - Idiopathic focal eosinophilic enteritis (IFEE) is a rare disease in the horse and
      few cases have been reported in the literature. The objective of this paper was
      to describe the clinical, surgical, histological features and post-operative
      progress of 12 horses with IFEE, a disease that had not been identified in the
      authors' hospital population prior to 2000. Diagnosis of IFEE was made at
      laparotomy and confirmed by histological examination of resected abnormal small
      intestine. In all 12 horses colic was associated with jejunal obstruction
      involving visibly striking and palpably thickened serosal plaques or
      circumferential constrictions. Surgical resection of affected intestine was
      performed in 10 horses, of which seven completely recovered. In one horse, on
      which surgical resection was not performed, ingesta re-obstructed post
      operatively at one of the lesions. Histological examination of resected
      intestines revealed, in all cases, severe transmural enteritis in which
      eosinophilic leucocytes were the predominant inflammatory cells. No helminths
      were identified and the cause of this lesion is not known. IFEE is an uncommon
      but significant cause of small intestinal obstruction for which surgical
      resection can be curative. The gross lesions may be under-recognised and
      histology is essential for diagnosis.

PMID- 16624718
TI  - Ultrasonography of the spleen in 50 healthy cows.
AB  - This paper describes the ultrasonographic appearance, location and size of the
      spleen in 50 healthy commercial milk cows destined for slaughter. The intercostal
      spaces of the left thoracic wall were scanned with a 3.5 MHz linear transducer.
      In each intercostal space, the appearance of the splenic parenchyma, the dorsal
      and ventral margins and the distance between them, and the diameter of the
      splenic vessels were recorded. The spleen was seen in intercostal spaces 7-12. It
      was 2.0-5.0 cm thick, and tapered ventrally. The splenic capsule appeared as an
      echogenic line. The splenic parenchyma consisted of numerous small regularly
      spaced echoes, and vessels within the parenchyma appeared as anechoic round to
      oval or elongated images. The long axis was oblique, running caudodorsal to
      cranioventral. The distance from the dorsal margin of the spleen to the midline
      of the back was greatest in the 7th intercostal space (60.9+/-6.81) and smallest
      in the 12th intercostal space (12.7+/-2.85 cm). The extent of the spleen was
      greatest in the 8th intercostal space (24.9+/-10.77 cm) and smallest in the 12th
      intercostal space (9.5+/-5.38 cm). The mean diameter of the splenic vessels
      ranged from 0.66+/-0.28 to 0.90+/-0.65 cm, depending on the intercostal space
      scanned. Ultrasonography of the spleen in healthy cows provides information that
      can be used as a reference when examining cattle with suspected splenic disease.

PMID- 16624719
TI  - The inducible form of heat shock protein 70 in the serum, colon and small
      intestine of the pig: comparison to conventional stress markers.
AB  - Modern rearing conditions may cause stress to pigs. At the cellular level all
      animals respond to stress by synthesizing heat shock proteins (HSP), which
      protect cells from injury. The objective of this study was to examine the
      concentrations of stress-inducible HSP72 in porcine small intestine and colon,
      known to be stress sensitive tissues, and to compare the findings with HSP72
      concentrations in serum and with conventional markers of stress, namely blood
      lactate and serum cortisol, glucose, free fatty acids and acute phase proteins.
      HSP72 in the colon correlated with serum HSP72 but there was a negative
      correlation with carcass weight (growth). The results suggest that the colon may
      be a significant source of serum HSP72, the concentration of which may reflect
      changes in the permeability of intestinal epithelium due to stressors, such as
      transport and handling.

PMID- 16624720
TI  - The efficacy of the bone markers osteocalcin and the carboxyterminal cross-linked
      telopeptide of type-I collagen in evaluating osteogenesis in a canine crural
      lengthening model.
AB  - The aim of the present study was to determine the efficacy of the bone markers
      osteocalcin (OC) and carboxyterminal cross-linked telopeptide of type-I collagen
      (ICTP) in evaluating new bone formation in the dog, using commercially available
      immunoassay kits. Dogs were randomly divided into three groups and a circular
      external skeletal fixation system (CESF) was mounted on the tibia. In the first
      group a distraction osteogenesis procedure of the crus was performed. The second
      group received an osteotomy without crural lengthening, whereas the third group
      served as a sham-operated control. Bone formation was assessed using
      densitometric image analysis of crural radiographs. Despite significant
      differences in the amount of newly formed bone, this finding was not reflected in
      the plasma levels of OC and ICTP. In conclusion, OC and ICTP were not efficacious
      as markers of bone formation and resorption during osteogenesis in this canine
      model.

PMID- 16624721
TI  - Characterisation of protein and antigen variability among Mycoplasma mycoides
      subsp. mycoides (LC) and Mycoplasma agalactiae field strains by SDS-PAGE and
      immunoblotting.
AB  - Mycoplasma mycoides subsp. mycoides (LC) (Mmm LC) and Mycoplasma agalactiae are
      the most important mycoplasma species involved in the contagious agalactia
      syndrome. A total of 25 field strains from Spain and the two type strains were
      analysed by SDS-PAGE and immunoblotting. Two polyclonal antisera (PAbs) raised
      against a pool of strains of each mycoplasma species were used. The results
      revealed a high degree of protein variability among the field strains. The type
      strain of Mmm LC appeared to be representative of the field strains of this
      species, whereas this was not the case with the M. agalactiae type strain.
      Whereas M. agalactiae is known to possess a gene family regulating surface
      antigen diversity, there is a need to study the mechanisms used byMmm LC to
      generate antigenic variability in more detail.

PMID- 16624722
TI  - Molecular detection of BHV-1 in artificially inoculated semen and in the semen of
      a latently infected bull treated with dexamethasone.
AB  - Two polymerase chain reaction (PCR) assays specific for glycoprotein B (gB) and
      glycoprotein E (gE) gene detection, respectively, were adopted for the detection
      of bovine herpesvirus-1 (BHV-1) in naturally infected bulls. The methods were
      tested on bovine semen artificially inoculated with BHV-1 and were compared with
      an optimised virus isolation method. Raw and extended semen samples were diluted
      in minimal essential medium (MEM) and spiked with equal dose of BHV-1. The
      extended semen was found to be more toxic for the cells than the raw semen, while
      the viral DNA could be detected by the PCR method in all tested dilutions of raw
      and extended semen samples. The sensitivity of both methods was compared also for
      BHV-1 detection in semen, nasal swabs and leucocytes of a seropositive bull in a
      different time period after virus reactivation with dexamethasone treatment. The
      sensitivity of virus detection by the PCR method was equivalent to that of virus
      isolation in cell culture. However, PCR was shown to be faster and easier to
      perform and may be a good alternative to virus isolation especially when bovine
      semen has to be screened for BHV-1 prior to artificial insemination.

PMID- 16624723
TI  - Serological and molecular comparison of Mannheimia haemolytica and Pasteurella
      trehalosi strains isolated from wild and domestic ruminants in the French Alps.
AB  - Over a period of 17 years, 84 bacterial isolates identified as Mannheimia
      haemolytica or M. glucosida, and 52 isolates identified as Pasteurella trehalosi
      were detected in the lungs of domestic and wild ruminants in the French Alps. The
      isolates were serotyped according to their surface capsular antigens, and those
      sharing common antigens were further characterized by pulsed field gel
      electrophoresis. The results showed that the bacterial isolates included in the
      study clustered according to the host species from which they were isolated.
      These findings indicate that the transmission of serotypes of M. haemolytica, M.
      glucosida or P. trehalosi from an animal host in which they are common to another
      species sharing the same geographical space may be a rare epidemiological event.

PMID- 16624724
TI  - The pharmacokinetic behaviour of marbofloxacin in Eurasian buzzards (Buteo buteo)
      after intraosseous administration.
AB  - This study reports on the administration of a single dose of marbofloxacin (2
      mg/kg) to five adult Eurasian buzzards (Buteo buteo) by the intraosseous (IO)
      route, which has been proposed as a rapid and efficient means for the parenteral
      delivery of antimicrobial drugs. The drug was rapidly absorbed. Peak
      marbofloxacin concentration (C(max)) in plasma and area under the concentration
      time curve (AUC) of 1.92+/-0.78 microg/mL and 8.53+/-2.73 microg h/mL,
      respectively. The time marbofloxacin remained in the plasma after IO
      administration was relatively short (elimination half-life, t(1/2beta)=4.91+/
      0.65 h; mean residence time (MRT)=5.38+/-0.57 h). Single dose marbofloxacin gave
      values for C(max)/minimum inhibitory concentration (MIC) of 19.2 and an AUC/MIC
      value of 85.3h after IO administration. The IO route appears to be practical and
      effective for the rapid delivery of marbofloxacin to buzzards.

PMID- 16624725
TI  - The role of rituximab in the treatment of canine lymphoma: an ex vivo evaluation.
AB  - Targeting the CD20 receptor that is common to many B-cell Non-Hodgkin's Lymphoma
      subtypes in people, rituximab is a chimeric monoclonal antibody which has
      significantly improved disease-free survival rates compared with the use of
      cytotoxic agents alone. This study evaluated ex vivo canine B cell binding and
      depletion by rituximab with flow cytometric technique as possible proof of
      concept for treatment of canine lymphoma. Despite immunohistochemistry supporting
      CD20 expression, rituximab did not bind or deplete canine B cells and it is
      unlikely that it will be added to the armamentarium of treatment options for
      canine lymphoma.

PMID- 16624726
TI  - Exclusion of DMRT1 as a candidate gene for canine SRY-negative XX sex reversal.
AB  - DMRT1, which encodes a zinc finger-like DNA binding motif, is a well-conserved
      gene that is involved in testis differentiation in a variety of mammalian and non
      mammalian vertebrates. The objective of this study was to determine whether a
      DMRT1 microsatellite marker allele is associated with the affected phenotype in a
      pedigree of canine SRY-negative XX sex reversal generated from an American Cocker
      spaniel founder. Ten affected dogs and their parents and grandparents were
      genotyped. Four alleles at this locus and five different genotypes were found in
      this pedigree. All affected dogs inherited this trait from the foundation sire of
      this colony. Thus, the disease-causing mutation should be identical by descent in
      all affected dogs. Six affected dogs were found to have genotypes at this locus
      that were different from those of the founder sire. These results indicate that
      DMRT1 is an unlikely candidate gene for SRY-negative XX sex reversal in this
      model.

PMID- 16624727
TI  - Elevated levels of fragmented laminin-5 gamma2-chain in bronchoalveolar lavage
      fluid from dogs with pulmonary eosinophilia.
AB  - Inflammation causes epithelial cell sloughing and basement membrane (BM) exposure
      in canine pulmonary eosinophilia (PE), leading to degradation of the epithelial
      cell attachment component, laminin-5 gamma2-chain, into small molecular weight
      fragments. The subsidence of inflammation after treatment down-regulates
      degradation. Laminin-5 gamma2-chain levels and molecular forms in bronchoalveolar
      lavage fluid (BALF) were analysed semiquantitatively by Western immunoblotting to
      compare PE affected (n=20) and healthy dogs (n=16) as well as PE dogs (n=6)
      before and after corticosteroid treatment. PE dogs expressed significantly
      elevated levels of total (P<0.01), 36 kDa (P<0.05) and 53 kDa (P<0.05) laminin-5
      gamma2-fragments. The 36 Da fragment decreased significantly (P<0.05) after
      treatment. The laminin-5 gamma2-chain degradation products may be linked to
      epithelial cell sloughing and BM exposure or healing.

PMID- 16624728
TI  - Detection of porcine circovirus type 1 in commercial pig vaccines using
      polymerase chain reaction.
AB  - The absence of extraneous viruses is a requirement in the quality control of
      vaccines for veterinary use in the European Pharmacopoeia. A polymerase chain
      reaction (PCR) assay for the detection of porcine circovirus type 1 (PCV1) and
      type 2 (PCV2) was evaluated in 18 commercial porcine vaccines. Since vaccine
      components may contain PCR enhancers or inhibitors, 13 of the studied vaccines
      (used as diluents) were subsequently spiked with different dilutions of PCV2 and
      tested by PCR. Although PCV2 DNA was not detected in any of the vaccines tested,
      PCV1 was detected in 2/18 vaccines (11%). Eleven out of 13 PCV2 spiked vaccines
      showed a positive PCR result. The lack of amplification observed in two spiked
      vaccines suggested that use of the PCR assay to detect PCV2 could depend on
      vaccine composition. The results of this exploratory study have demonstrated that
      PCR is a rapid and fairly sensitive method for the detection of porcine
      circoviruses as extraneous agents in vaccine products and can be used in the
      quality control of pig vaccines. The study has also indicated the need for
      optimising the sensitivity of PCR methods for PCV genome detection in vaccine
      products.

PMID- 16624729
TI  - An investigation into the role of Chlamydophila spp. in bovine upper respiratory
      tract disease.
AB  - An outbreak of upper respiratory tract disease was investigated in a group of 17
      housed home-bred calves on a mixed dairy, beef and sheep farm in Devon.
      Conjunctival swabs were collected and tested for Chlamydophila spp. DNA using a
      PCR test that detects Chlamydophila abortus and Chlamydophila psittaci. Six of
      the calves tested gave a positive result. Further epidemiological observations
      and laboratory testing indicated that the adult dairy cows, from which the
      affected calves originated, were the most likely source of infection.

PMID- 16624730
TI  - Expression of thioredoxin-binding protein-2/vitamin D3 upregulated protein-1 in
      peripheral blood eosinophils of asthma patients.
AB  - OBJECTIVE: To investigate the expression of vitamin D3 upregulated protein-1
      (VDUP1) in peripheral eosinophils at different stages of asthma and its
      correlation with clinical manifestations of asthma. METHODS: Fourteen normal
      volunteers and 51 mild to moderate asthma patients, including 16 untreated
      patients with asthma attack and 35 with asthma remission by continuously
      corticosterone inhalation. The symptom severity and pulmonary function indices
      were evaluated and induced sputum eosinophil counts and blood eosinophil count
      measured. VDUP1 and beta-actin gene fragments were amplified simultaneously by RT
      PCR from the total RNA of peripheral eosinophils, and 10 microl of the RT-PCR
      product underwent agarose gel electrophoresis and the VDUP1/beta-actin ratio was
      obtained by Gel-Pro software. RESULTS: VDUP1/beta-actin ratio significantly
      decreased in untreated patients with asthma attacks in comparison with normal
      volunteers (0.314+/-0.242 vs 0.532 +/-0.279) but not in patients with asthma
      remission (0.612+/-0.381). In the former patients, a positive correlation of
      VDUP1/beta-actin ratio was found with FEV1.0% (r=0.587, P=0.046) and %PEF
      (r=0.563, P=0.033), whereas an inverse one observed with sputum eosinophil count
      (r=-0.436, P=0.049). CONCLUSION: VDUP1 expression in the eosinophils correlates
      to eosinophil activation and may influence the disease severity of asthma
      patients.

PMID- 16624731
TI  - Epigallocatechin gallate protects dopaminergic neurons against 1-methyl-4- phenyl
      1,2,3,6-tetrahydropyridine-induced neurotoxicity by inhibiting microglial cell
      activation.
AB  - OBJECTIVE: To observe whether the dopaminergic neuroprotective effect of (-)
      epigallocatechin gallate (EGCG) is associated with its inhibition of microglial
      cell activation in vivo. METHODS: The effects of EGCG at different doses on
      dopaminergic neuronal survival were tested in a methyl-4-phenyl-pyridinium (MPP+)
      induced dopaminergic neuronal injury model in the primary mesencephalic cell
      cultures. With unbiased stereological method, tyrosine hydroxylase-immunoreactive
      (TH-ir) cells were counted in the A8, A9 and A10 regions of the substantia nigra
      (SN) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57BL/6 mice.
      The effect of EGCG on microglial activation in the SN was also investigated.
      RESULTS: Pretreatment with EGCG (1 to 100 micromol/L) significantly attenuated
      MPP+-induced TH-ir cell loss by 22.2% to 80.5% in the mesencephalic cell
      cultures. In MPTP-treated C57BL/6 mice, EGCG at a low concentration (1 mg/kg)
      provided significant protection against MPTP-induced TH-ir cell loss by 50.9% in
      the whole nigral area and by 71.7% in the A9 region. EGCG at 5 mg/kg showed more
      prominent protective effect than at 1 or 10 mg/kg. EGCG pretreatment
      significantly inhibited microglial activation and CD11b expression induced by
      MPTP. CONCLUSION: EGCG exerts potent dopaminergic neuroprotective activity by
      means of microglial inhibition, which shed light on the potential use of EGCG in
      treatment of Parkinson's disease.

PMID- 16624732
TI  - [Protective effect of selenium against T-2 toxin-induced inhibition of
      chondrocyte aggrecan and collagen II synthesis].
AB  - OBJECTIVE: To study the inhibitory effect of T-2 toxin on the expression of
      aggrecan and collagen II in chondrocytes and the protection of selenium against
      this effect. METHODS: Human chondrocytes cultured in vitro were treated with T-2
      toxin at different concentrations for varied time periods (1-5 days), and the
      cell viability was measured by MTT assay. Aggrecan expression was detected by
      toluidine blue staining and collagen II expression by immunostaining using
      monoclonal antibody of collagen. Aggrecan and collagen II mRNA expressions were
      measured by semiquantitative RT-PCR. RESULTS: T-2 toxin dose- and time
      dependently affected chondrocyte viability within the concentration range of
      0.001-2 mg/L, the prolonged treatment time further enhanced the dose dependence
      of the inhibitory effect. T-2 toxin lowered aggrecan and collagen II synthesis in
      the chondrocytes and reduced their mRNA expressions. Selenium could partly
      attenuate the inhibitory effects of T-2 toxin on aggrecan mRNA expression, but
      showed no such effect against T-2-induced collagen II expression. CONCLUSION: T-2
      toxin can obviously inhibit aggrecan and collagen II synthesis in human
      chondrocytes, and selenium can partly antagonize the inhibitory effects of T-2
      toxin on aggrecan.

PMID- 16624733
TI  - [Microcystin-LR induces apoptosis in L-02 cell line].
AB  - OBJECTIVE: To investigate the toxicological mechanism of microcystin-LR (MCLR) on
      L-02 cells. METHODS: L-02 cells was treated with MCLR at different concentrations
      and the subsequent changes such as cell proliferation (MTT assay), morphology,
      lactate dehydrogenase (LDH) leakage, apoptosis rate and apoptosis-related gene
      expression were examined. RESULTS: MTT assay showed that MCLR mildly inhibited
      the cell growth within the initial 24 h of treatment but enhanced the cell
      viability after that till 60 h in a time- and dose-dependent manner. LDH leakage
      underwent no marked changes in response to 48-hour MCLR treatment but increased
      upon prolonged treatment for 60 h, indicating the presence of oxidative damage.
      After a 48-h treatment with MCLR at 50 microg/ml, obvious apoptosis of L-02 cells
      occurred as manifested by cell rounding, detachment from the substrate, cell
      shrinkage and membrane blebbing. The apoptosis rates were rather low (between 22%
      and 29%) after treatment with MCLR at different concentrations for 36 h, and
      increased to as much as 80% after a 60-h treatment with 50 microg/ml MCLR. The
      expressions of p53 and bcl-2 increased in the cells after treatment with high
      concentration MCLR, suggesting that MCLR up-regulated the expression levels of
      the two proteins. CONCLUSION: MCLR can induce apoptosis and up-regulate p53 and
      bcl-2 expressions in human normal liver cell line L-02.

PMID- 16624734
TI  - [Noise image segmentation based on generalized fuzzy Gibbs random field].
AB  - In order to segment the blurred image with large noise, the authors propose a new
      Bayesian image segmentation method based on generalized fuzzy Gibbs random field.
      Based on the generalized fuzzy set, the new method introduces generalized fuzzy
      membership into Gibbs potential function and the potential function is redefined
      to obtain the new segmentation model. The optimal processing is executed through
      iterative conditional modes (ICM). The experiment results showed that the new
      approach could effectively segment the degenerated images.

PMID- 16624735
TI  - [Functional changes of dendritic cells after infection by recombinant retrovirus
      carrying human telomerase reverse transcriptase gene fragment].
AB  - OBJECTIVE: To observe the functional changes of dendritic cells (DCs) after
      infection by recombinant retrovirus carrying human telomerase reverse
      transcriptase (hTERT) gene fragment. METHODS: Interleukin-12 (IL-12) levels in DC
      culture supernatant was determined by enzyme-linked immunosorbent assay (ELISA).
      The abilities of DCs infected with recombinant retrovirus carrying hTERT gene
      (hTERT-DCs) and non-infected DCs (N-DCs) to stimulate allogeneic lymphocyte
      proliferation were evaluated with mixed leukocytes reaction (MLR), and the
      surface markers of DCs including CD80, CD83, CD86 and HLA-DR were detected by
      flow cytometry. Cytotoxic T lymphocyte (CTL) assay was performed with CytoTox 96
      non-radioactive cytoxicity assay. RESULTS: Compared with N-DCs, hTERT-DCs showed
      no significant changes in IL-12 secretion and capacity to stimulate allogeneic
      lymphocytes reaction, but had significantly lower CD83 expression. Specific CTLs
      induced by hTERT-DCs resulted in higher cytotoxicity against telomerase-positive
      target cells than that against the negative target cells. CONCLUSION: Infection
      with the recombinant retrovirus carrying hTERT fragment may jeopardize the
      maturation of DCs, which, however, still retain their capacity to activate and
      stimulate lymphocyte proliferation and to prime autologous T lymphocytes to
      generate specific CTL against hTERT.

PMID- 16624736
TI  - [Apoptosis of glioma cell line U251 induced by small interfering RNA targeting
      survivin].
AB  - OBJECTIVE: To construct recombinant expression vectors of small interfering RNA
      (siRNA) targeting survivin and investigate apoptosis of glioma cell line U251
      mediated by the survivin-targeting siRNA. METHODS: According to the sequence of
      the coding region of survivin gene, two strings of 19 nucleotides of inverted
      sequence flanking the loop sequence of two complementary 9-base oligonucleotides
      were designed and synthesized to form hairpin construct as the DNA templates for
      the target siRNA. The siRNA templates were cloned into siRNA expression vector
      pGenesil-1, and the resulted vector pGenesil-1/survivin was transfected into U251
      cells using Metafectene following the standard protocols. Real-time PCR and
      Western blotting were performed to evaluate survivin gene silencing induced by
      siRNA transfection at the RNA and protein levels, respectively. Flow cytometry
      analysis with Annexin-V/PI double staining was used to determine the cell
      apoptosis. RESULTS: Real-time RT-PCR and Western blotting revealed significantly
      lowered survivin expression at both RNA and protein levels in transfected U251
      cells, which exhibited a significantly higher apoptosis rate after transfection
      as shown by flow cytometry analysis. CONCLUSION: RNA interference mediated by the
      siRNA expression vector pGenesi-l/survivin can significantly reduce survivin
      expression and induce remarkable apoptosis in U251 cells.

PMID- 16624737
TI  - [In vitro killing effect of adenovirus-mediated fusion gene system driven by KDR
      promoter on gastric cancer cells].
AB  - OBJECTIVE: To evaluate the killing effect of adenovirus(Ad)-mediated double
      suicide gene driven by kinase domain-containing receptor (KDR) promoter on
      gastric cancer MGC-803 cells. METHODS: The 293 packaging cells were transfected
      by the plasmids pAdEasy-KDR-CDglyTK to generate infectious viruses. The gastric
      cancer MGC-803 cells were infected by the Ad followed by treatment with 5-FC
      and/or ganciclovir at different concentrations. The cell-killing effects were
      evaluated and the bystander effects analyzed after coculture of the cells without
      AdKDR-CDglyTK infection with the infected cells at different ratios. The cell
      cycle distribution was detected by flow cytometry and the pathological changes of
      the cells were observed by electron microscopy. RESULTS: The infection rate of
      the resultant recombinant Ad in the cells increased gradually with increment of
      the multiplicity of infection (MOI) of the Ads. The killing effect of CD/TK
      fusion gene on the MGC-803 cells was much stronger than that of either of the
      single suicide gene (P<0.001), and considerable bystander effect was observed.
      The Ad infection caused MGC-803 cell growth arrest at G(1) phase with onset of
      apoptotic and necrotic morphologies of the cells as seen under electron
      microscope. CONCLUSION: The CD/TK fusion gene system driven by the KDR promoter
      possesses effective killing effect on the KDR-expressing gastric cancer MGC-803
      cells.

PMID- 16624738
TI  - [Resveratrol induces HepG2 cell apoptosis by depolarizing mitochondrial
      membrane].
AB  - OBJECTIVE: To investigate the effects of resveratrol on the proliferation,
      apoptosis, mitochondrial membrane potential and cell morphology of human liver
      cancer cell line HepG2. METHODS: The changes in HepG2 cell growth and
      proliferation in response to resveratrol treatment were evaluated by MTT assay,
      and resveratrol-induced apoptosis of HepG2 cells was investigated by flow
      cytometry. Inverted microscope and electron microscope were employed for
      observing morphological changes of the treated cells. The whole-cell
      mitochondrial membrane potential was measured in separate experiments using two
      fluorimetric probes, rhodamine123 and TMRE, respectively. HepG2 cells treated
      with rhodamine123 were analyzed by flow cytometry and cells treated with TMRE by
      confocal microscope. RESULTS: MTT assay showed that low concentrations of
      resveratrol produced no significant effect on the growth of HepG2 cells, whereas
      at high concentrations, resveratrol could obviously inhibit the cell growth in a
      time- and dose-dependent manner. Resveratrol also induced apoptosis of HepG2
      cells, and after a 24-hour treatment, resveratrol caused sharp increment of the
      mitochondria membrane potential. CONCLUSION: Resveratrol is capable of inhibiting
      the proliferation of HepG2 cells and inducing cell apoptosis by depolarizing
      mitochondrial membrane potential.

PMID- 16624739
TI  - [Adsorption condition optimization for anti-HBsAg Fab fragment separation and
      purification from E. coli using Streamline SP].
AB  - OBJECTIVE: To optimize the adsorption condition of cation-exchange
      chromatographic media Streamline SP for separation and purification of anti-HBsAg
      Fab fragment from E. coli. METHODS: The adsorption of the target protein for
      separation and purification by the cation-exchange chromatographic media
      Streamline SP was tested using test tube method in balanced buffer solution with
      different pH values and ion concentrations. The adsorption effect was then
      verified by cation-exchange chromatography using 1-ml Streamline SP prepacked
      column and 28-ml Streamline SP self-assembly column. RESULTS: According to the
      experiment results of test tube method, the loading buffer with pH of 4.4 and
      ionic concentration of 100 to 600 mmol/L could achieve optimal target protein
      adsorption effect by cation-exchange chromatographic media Streamline SP, as
      verified by cation-exchange chromatography with 1-ml SP prepacked column and 28
      ml Streamline SP self-assembly column. CONCLUSION: The optimal condition of
      cation-exchange chromatography selected by test tube method can be applied for
      separation and purification of anti-HBsAg Fab fragment from E. coli.

PMID- 16624740
TI  - [Analysis of allele frequencies of 6 short tandem repeat loci on chromosome 12 in
      patients with Kashing-Beck disease].
AB  - OBJECTIVE: To analyze the allele frequencies of 6 STR loci (D12S358, D12S1675,
      D12S1663, D12S1697, D12S16725 and D12S1613) on chromosome 12 among KBD patients
      and residents in the KBD and non-KBD areas. METHODS: EDTA-blood samples were
      collected from 146 unrelated Chinese Han individuals in Shaanxi Province
      including 57 KBD patients, 48 control subjects living in the Kashing-Beck
      disease(KBD) area and 48 in the non-KBD area. The DNA samples were extracted and
      amplified by PCR, and the PCR products were analyzed by ABI 3100 Genetic
      Analyzer. RESULTS: In KBD patients, the allele number for the 6 STR loci
      (D12S358, D12S1675, D12S1663, D12S1697, D12S16725 and D12S1613) was 7, 7, 7, 10,
      12 and 8, and the genotype number were 13, 12, 9, 17, 19 and 10, respectively; in
      the residents in KBD area, the allele number was 7, 5, 7, 9, 13 and 9, and the
      genotype number 12, 10, 12, 19, 16 and 8; in residents in non-KBD area, the
      allele number was 7, 5, 5, 12, 8 and 9, and the genotype number 17, 16, 8, 22, 14
      and 8. There were significant differences in the allele frequencies in the
      D12S1725 loci between KBD patients and residents living in KBD area (P=0.0119)
      and the non-KBD area (P=0.0050), but no significant difference in other 5 loci
      among the 3 groups. CONCLUSION: KBD patients have significantly different allele
      distribution patterns in the D12S1725 loci from the control subjects.

PMID- 16624741
TI  - [Culture condition optimization of engineered E. coli BL21/pET-11c/hIL-2-mGM
      CSF].
AB  - OBJECTIVE: To optimize the culture condition of engineered E.coli to improve its
      expression efficiency of hIL-2-mGM-CSF protein. METHODS: According to an
      orthogonal Latin square experiment design, the effects of the culture medium,
      temperature and IPTG concentration at different levels on the efficiency of the
      engineered E. coli were evaluated for its expression of hIL-2-mGM-CSF protein.
      The results of SDS-PAGE were analyzed with software and the culture conditions
      derived from the experimental results were tested in independent cultures. The
      optimal culture condition was used in three large-scale cultures and the results
      were compared with that of routine cultures. RESULTS: The cultures with TH broth
      yielded higher relative expression quantity of the target protein than those with
      2 x YT and LB medium. Compared with the induction temperature at 37 degrees C,
      induction at 42 degrees C significantly improved the expression efficiency of the
      target protein. IPTG at the concentration as low as 0.3 mmol/L produced better
      effect than 1.0 mmol/L IPTG. Statistical analysis suggested that the optimized
      culture conditions could obviously improve the expression efficiency of the
      target protein. Large scale cultures with the optimized culture condition
      resulted in a 5-fold improvement of the relative expression quantity of the
      protein, which accounted for over 29% of total bacterial protein. CONCLUSION: The
      optimized culture condition of the engineered E. coli can remarkably increase the
      expression efficiency of hIL-2-mGM-CSF, which may facilitate the subsequent
      purification and functional study of the protein.

PMID- 16624742
TI  - [Effect of Bay K 8644 on arteriole smooth muscle cell membrane potential in rats
      with severe hemorrhagic shock].
AB  - OBJECTIVE: To investigate the effect of Ca(2+) influx through L-type Ca(2+)
      channels on normal and hyperpolarized membrane potential of arteriole smooth
      muscle cells (ASMCs) in rats. METHODS: The ASMCs isolated from normal rats and
      those with severe hemorrhagic shock were labeled with DiBAC4 (3) for membrane
      potential detection. RESULTS: Ca(2+) influx caused hyperpolarization of the
      membrane potential in the normal ASMCs but depolarization in the cells from rats
      with hemorrhagic shock, and this effect could be inhibited by TEA. CONCLUSION:
      Ca(2+)-activated potassium channels activated by Ca(2+) influx through L-type
      Ca(2+) channels in normal ASMCs to cause hyperpolarization but leads directly to
      membrane potential depolarization in ASMCs from rats with severe hemorrhagic
      shock. This finding can be meaningful for treatment of vascular hyporeactivity in
      advanced stage of severe shock.

PMID- 16624743
TI  - [Preparation and identification of monoclonal antibodies against Helicobacter
      pylori].
AB  - OBJECTIVE: To prepare and identify monoclonal antibodies (mAbs) against
      Helicobacter pylori (Hp). METHODS: BALB/c mice were immunized with the
      supernatant and precipitation of cultured Hp after ultrasonication and mAbs were
      obtained by means of hybridoma technique. The resultant mAbs was evaluated for
      subtype, titer, affinity, and further identified with Lpp20, HspA, urease A,
      CagA, urease B, and catalase prepared by recombinant expression. RESULTS: Totally
      34 hybridoma cell lines were established which secreted specific mAbs, including
      31 against the supernatant and 3 against the precipitation of Hp, and the
      prepared mAbs showed specific reaction against Lpp20 (3 strains), HspA (2
      strains), urease A (4 strains), CagA (1 strain), urease B (5 strains), and
      catalase (2 strains) antigens, respectively. The mAbs was all identified as
      immunoglobulin G1 (IgG1) and theirs titer in the culture supernatant and ascites
      was 1:16 to 1:32 and 1:32000 to 1:64000 respectively with affinity constants
      (K(aff)) ranging from 1 x 10(-10) to 5.2 x 10(-12) mol/L. CONCLUSION: The mAbs
      specially against Hp have been obtained, which may facilitate further study of
      detection and vaccine development of Hp.

PMID- 16624744
TI  - [Relationship between serum interleukin-10 and insulin resistance in metabolic
      syndrome].
AB  - OBJECTIVE: To investigate the relationship between serum interleukin-10 (IL-10)
      level and insulin resistance (IR) in patients with metabolic syndrome (MS).
      METHODS: Eighteen MS subjects and 18 age-matched normal subjects were enrolled.
      IR was evaluated by hyperinsulinemic-euglycemic clamp technique and serum IL-10
      level measured by ELISA. Pearson's correlation analysis was used to investigate
      the relationship between serum IL-10 level and IR. RESULTS: Serum IL-10 levels
      were significantly higher in patients with MS than in the controls [1.3 (0.8/3.1)
      pg/ml vs 2.4 (1.1/4.5) pg/ml, P<0.05], and glucose metabolic rate (M value)
      derived from hyperinsulinemic-euglycemic clamp technique was lower in MS subjects
      than in controls [(5.76+/-1.81) mg/kg.min vs (8.39+/-1.25) mg/kg.min], P<0.05].
      Serum IL-10 levels showed a positive correlation with M value (P<0.05).
      CONCLUSION: Patients with MS have greater IR and lower serum IL-10 levels than
      normal subjects, and lowered IL-10 levels might be involved in the pathogenesis
      of IR in MS.

PMID- 16624745
TI  - [Toxicity of photoactivated insecticide K-01 to the larvae of Aedes albopictus].
AB  - OBJECTIVE: To evaluate the toxicity of photoactivated insecticide K-01 to the
      larvae of Aedes albopictus and observe the histopathological changes in the
      larvae. METHODS: The number of dead larvae was recorded after application of K-01
      at different concentrations under different illumination conditions. The content
      variation of the midgut, malpighian tubules and fat bodies in the larvae was
      observed microscopically, and the genomic DNA of the larvae was extracted for
      electrophoresis to identify the target bands. RESULTS: The maximum larvae-killing
      effect was achieved with 50 mg/ml K-01 applied under sunlight (100% killing 24
      hours after application). Optical microscopic observation of the killed larvae
      revealed severe damage of the mid-intestinal cells that showed disintegration and
      elongation. Distinct vacuoles were observed in the fat body cells, in which red
      droplets were seen to assemble around the cell nuclei. The result of 0.8% agarose
      gel electrophoresis of the larvae genomic DNA presented typical ladder patterns,
      suggesting the presence of cell apoptosis. CONCLUSION: K-01 is an effective
      photoactivated insecticide.

PMID- 16624746
TI  - [Whole-body fluorescent imaging of the growth and metastasis of GFP-expressing
      bladder tumors].
AB  - OBJECTIVE: To label a human bladder cancer cell line and establish a novel human
      bladder cancer mouse model. METHODS: T-24 cells, a human bladder transitional
      cell carcinoma cell line, were transfected with GFP plasmid to screen stable GFP
      expressing clones. The latter were implanted into the wall of the bladder or the
      subcutaneous tissue of the neck of nude mice. The growth, invasion, and
      metastasis of the implanted tumor were observed and evaluated with whole-body
      optical imaging system. The findings were compared with those of HE staining on
      routine paraffin sections. RESULTS: GFP-labeled tumor cells displayed green
      fluorescence under fluorescent microscopy and showed stable GFP expression in
      vitro and in vivo. One week after in situ transplantation of 5 x 10(5) T24 cells,
      the new bladder cancer was observed and evaluated under whole-body optical
      imaging system. Two weeks later, the new bladder tumor could be palpated, and 4
      weeks later, metastasis to regional drainage lymph nodes in the pelvic and
      retroperitoneal lymph nodes occurred. The growth and metastasis of the implant
      bladder tumor were easily observed and accurately evaluated by fluorescent
      microscope. CONCLUSION: GFP-labeled tumor cells display green fluorescence under
      fluorescent microscopy and show stable GFP expression. GFP-labeled T-24 cells and
      the novel human bladder cancer model described hereby provide a simple and
      reliable means for studying human bladder cancer in vivo.

PMID- 16624747
TI  - [Constitutive activation of signal transducers and activators of transcription 3
      and expression of its target gene products in human ESCC cell line].
AB  - OBJECTIVE: To investigate the expression of signal transducers and activators of
      transcription 3 (STAT3) and its target gene products including vascular
      endothelial growth factor (VEGF) and Bcl-2 in two human esophageal squamous cell
      carcinoma (ESCC) cell lines for understanding whether STAT3 signaling
      transduction pathway was constitutively activated in ESCC cell lines. METHODS:
      Western blotting was used to determine the protein levels of STAT3, p-STAT3
      (activated STAT3), VEGF and Bcl-2 in two ESCC cell lines (EC9706 and Eca109).
      Nuclear proteins from the ESCC cell lines were extracted to evaluate the DNA
      binding activity by electrophoretic mobility gel shift assay (EMSA). RT-PCR was
      used to detect the mRNA of STAT3, VEGF and Bcl-2. RESULTS: Western blotting and
      RT-PCR revealed that STAT3, VEGF and Bcl-2 protein and mRNA were overexpressed in
      the two ESCC cell lines, which contained constitutively activated STAT3 signaling
      transduction pathway. The results of EMSA of the nuclear protein showed high DNA
      binding activity of STAT3. CONCLUSION: STAT3 signaling transduction pathway is
      constitutively activated in human ESCC cell lines, suggesting that STAT3 may play
      a critical role in the carcinogenesis of the esophagus.

PMID- 16624748
TI  - [Morphological changes of ECV304 cells infected by herpes simplex virus type 2].
AB  - OBJECTIVE: To observe the pathological changes and morphological alterations of
      ECV304 cells after the infection by herpes simplex virus type 2 (HSV-2) in vitro.
      METHODS: Passaged ECV304 cells were infected with HSV-2, TCID50 and morphological
      changes were observed by optical microscopy and tissue staining. RESULTS: One day
      after HSV-2 infection, swelling, rounding, and increase of thickened cytoplasmic
      granules occurred in the ECV304 cells, and on day 2, cell fusion was observed
      with weakened nuclear staining. CONCLUSION: ECV304 cells mostly undergo necrosis
      after HSV-2 infection without obvious evidence of cell apoptosis.

PMID- 16624749
TI  - [Effect of N-acetyl-cysteine and depakine pretreatment on ferrous chloride
      induced membrane potential and peroxidate changes in rat cortex neurons].
AB  - OBJECTIVE: To investigate the effect of N-acetyl-cysteine (NAC) and depakine (DP)
      on the changes of membrane potential and peroxidate in rat cortex neurons exposed
      to ferrous chloride (FeCl(2)). METHODS: Cultured cortex neurons of newly born SD
      rats were randomly divided into control group (PBS group), model group (FeCl(2)
      group), NAC pretreatment group (NAC group), DP pretreatment group (DP group) and
      NAC+DP pretreatment group (NAC+DP group). In the latter three groups, NAC (0.08
      mg/ml) and DP (0.1 mg/ml) were added in the cell culture 2 and 3 h before FeCl(2)
      (1 mmol/L) exposure, respectively. After exposure to FeCl(2), the membrane
      potential of the neurons was detected with fluorescent dye DiBAC4(3) (bis-(1,3
      dibutylbarbituric acid) trimethine oxonol), and the peroxidate level with 2,7
      dichlorofluorescin diacetate (H(2)DCF) by laser confocal scanning microscope
      (LCSM) and nuclear factor-KappaB (NF-KappaB) level with immunocytochemistry.
      RESULTS: Compared with FeCl(2) group, the expression of NF-KappaB and peroxidate
      level in the neurons were decreased significantly in NAC and NAC+DP groups
      (P<0.01), but not in DP group (P>0.05). FeCl(2) depolarized the membrane
      potential and increased the expression of NF-KappaB in the neurons. Compared with
      FeCl(2) group, significant changes in the membrane potential were observed in DP
      and NAC+DP groups (P<0.01) but not in NAC or PBS group (P>0.05). CONCLUSION: Both
      NAC and DP can protect the neurons from FeCl(2)-induced damage but through
      different pathways, and their combined use can significantly alleviate neuronal
      damages due to FeCl(2) exposure. Antioxidants such as NAC in combination with
      antiepileptic drugs may produce favorable effect in prevention and treatment of
      posttraumatic epilepsy.

PMID- 16624750
TI  - [Effect of saikosaponins on glial fibrillary acidic protein expression in
      hippocampal astrocytes of pentetrazole-induced chronic kindling rats].
AB  - OBJECTIVE: To study the effect of saikosaponins, the active ingredients of
      Bupleurum chinense DC, on glial fibrillary acidic protein (GFAP) expression in
      hippocampal astrocytes of chronic kindling rats induced by pentetrazole (PTZ).
      METHODS: Forty-eight healthy Sprague-Dawley rats were randomized into 6 equal
      groups, namely the blank control group (Group A), normal saline group (Group B),
      sodium valproate group (Group C), and 3 saikosaponins groups of high, medium and
      small doses (Groups D, E, and F, respectively). The rats (except those in Group
      A) received intraperitoneal injection of PTZ to induce chronic kindling 1 h after
      the respective agents as indicated were administered intragastrically on a daily
      basis for 4 consecutive weeks. Upon completion of the treatment course, the rats
      were sacrificed and the brain tissues were sampled, sliced and stained for
      immunohistochemical examination. The results were analyzed to calculate the
      positive cell count, cross-sectional area of the cells and the gray scale.
      RESULTS: In group B, the positive cell population and cross-sectional area of the
      positive cells were the greatest among the groups (P<0.01), but the positive cell
      gray scale of the CA1 and CA2 regions and the dentate gyrus (DG) of the
      hippocampus was the lowest. The CA1 region of Group B was significantly different
      from that of groups A, C and D (P<0.01), and the CA2 region different from groups
      A, C, D and E (P<0.05), while the DG different from group F (P<0.05) and groups
      A, C, D and E (P<0.01). CONCLUSION: In chronic kindling rats induced by PTZ, GFAP
      overexpression can be inhibited by saikosaponins, which suppress the abnormal
      activation of hippocampal astrocyte of the kindling rats.

PMID- 16624751
TI  - [A preliminary study of beam weight optimization of intensity-modulated radiation
      therapy with genetic algorithm].
AB  - To study the method for dose calculation and beam weight optimization of
      intensity-modulated radiation therapy (IMRT). METHODS: The IMRT dose calculation
      model based on two-dimensional convolution was constructed, the program of dose
      calculation and beam weight optimization with genetic algorithm was written with
      Visual c#.Net, and the optimization results were analyzed. RESULTS: Genetic
      algorithm optimization of beam weights can produce highly conformal dose
      distributions within a clinically acceptable computation time. CONCLUSION:
      Genetic algorithm is valid and efficient in IMRT beam weight optimization, which
      may facilitate IMRT treatment planning.

PMID- 16624752
TI  - [Efficacy of 188Re-herceptin radioimmunotherapy in nude mouse model of
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the effect of radioimmunotherapy with (188)Re-labeled
      herceptin in nude mice bearing nasopharyngeal carcinoma expressing HER2/neu proto
      oncogene and explore the feasibility of (188)Re-herceptin for use as a chemical
      therapeutic and radioimmunotherapeutic agent. METHODS: A direct radiolabeling
      method was used to prepare (188)Re-Herceptin. Thirty-two nude mice bearing
      nasopharyngeal carcinoma were randomized into 4 groups (n=8) to receive single
      intravenous injection of (188)Re-Herceptin, intratumoral injection of (188)Re
      Herceptin, (188)Re-nmIgG and (188)Re, respectively, all at the equivalent dose of
      11.1 MBq (50 microl). Another 5 tumor-bearing mice received only intratumoral
      injection of 50 microl normal saline to serve as the control group. Two days
      after the injections, 3 mice were selected from each group (except for the
      control group) for biodistribution observation, and the rest mice were monitored
      for 4 consecutive weeks for tumor volume changes. Pathological examination of the
      tumor tissues was also performed. RESULTS: The radioactivity uptake in the tumor
      was significantly greater whereas normal organ uptake significantly lower in the
      nude mice receiving intratumoral (188)Re-Herceptin injection than in those with
      intravenous (188)Re-Herceptin injection (11.53%ID/g vs 2.79%ID/g at 48 h).
      Intratumoral (188)Re-Herceptin injection caused greater inhibition of tumor
      growth at the 4th week as compared to the intravenous administration. CONCLUSION:
      Intratumoral (188)Re-Herceptin administration can significantly inhibit the
      development of nasopharyngeal carcinoma in mice, and may potentially serve as a
      new clinical option of regional therapy for treating nasopharyngeal carcinoma
      overexpressing HER2/neu.

PMID- 16624753
TI  - [Variability analysis of S2 gene of SARS-CoV].
AB  - OBJECTIVE: To determine the sequence of S2 gene of SARS-associated coronavirus
      (SARS-CoV) GD322 and analyze the phyletic evolution of S2 gene. METHOD: S2 gene
      fragment was amplified from SARS-CoV GD322 genome with RT-PCR and ligated to pGEM
      T vector for sequence analysis after transformation of the plasmid into E. coli
      DH5a. The variability of S2 genes and S2 proteins from 12 strains isolated in the
      early, intermediate and advanced stages of the SARS outbreak were analyzed and
      the phylogenetic tree was constructed with Lasergene, Clustal X, DNAman and
      Treeview. T cell antigen epitopes of S2 protein were predicted on the basis of
      Internet database. RESULT: With the epidemic spread of SARS-CoV, the S2 genes of
      the virus tended to become stable. Homology of S2 genes of SARS-CoV isolated in
      advanced stage of the outbreak reached 99.9%. Prediction of T cell antigen
      epitope showed that mutation at the 57th amino acid effected T cell antigen
      epitope. CONCLUSION: S2 gene of GD322 SARS-CoV is relatively stable during the
      epidemic spread of the virus, and mutation at the 57th amino acids of S2 protein
      may affect the T cell antigen epitope.

PMID- 16624754
TI  - [Detection of mdr1 gene by real-time fluorescence quantitative polymerase chain
      reaction using Taq Man-MGB probe].
AB  - OBJECTIVE: Primer Express 2.0 software was used to design the primers and the MGB
      probe. With the plasmid pHaMDR1/A containing mdr1 cDNA as the template, we
      established a real-time fluorescent quantitative polymerase chain reaction
      system, which, at the template concentration of 3.061 x 10(3) to 3.061 x 10(9)
      cps/ml, had a correlation coefficient of 0.988243 between template concentration
      and threshold cycle value. This PCR method allows sensitive, specific and
      quantitative detection of human mdr1 gene.

PMID- 16624755
TI  - [Construction and identification of genomic cDNA subclones of dengue 2 virus NGC
      strain].
AB  - OBJECTIVE: To construct the cDNA subclones spanning the entire genome of dengue 2
      virus NGC strain for further construction of full-length infectious viral cDNA
      clone. METHODS: Two pairs of primers were designed according to the restriction
      endonuclease sites in the viral genome of dengue 2 virus NGC strain. After viral
      RNA extraction from the brain of infected new-born mice, two parts of full-length
      viral cDNA were amplified by long RT-PCR and cloned into the vector pCR-XL-TOPO.
      The partial sequence of the recombinant plasmid was determined. RESULTS AND
      CONCLUSION: Sequence analysis and digestion with restriction enzymes demonstrated
      that the two cDNA subclones were specific for dengue 2 virus NGC strain,
      suggesting the successful construction of the two cDNA subclones of dengue 2
      virus NGC strain.

PMID- 16624756
TI  - [Cloning and prokaryotic expression of the gene encoding PGRP domain of mouse
      long peptidoglycan recognition protein].
AB  - OBJECTIVE: To clone the gene coding for the peptidoglycan recognition protein
      (PGRP) domain (PGRPd) of mouse long PGRP (mPGRP-L) and express the protein in E.
      coli. METHODS: The cDNA fragment encoding PGRPd of mPGRP-L was obtained by RT-PCR
      from the total RNA of Balb/C mouse liver cells and cloned into pUCm-T vector. The
      recombinant plasmid were identified by PCR, restriction endonucleases and
      sequence analysis. The PGRPd gene fragment was amplified by PCR from the
      recombinant plasmid, inserted into pQE-30 vector and transformed into E. coli
      strain M15, and the expressed PGRPd protein was purified. RESULTS: A cDNA
      fragment of about 500 bp was amplified by RT-PCR and the recombinant plasmid,
      pmPGRPd, was constructed by linking the fragment to pUCm-T vector. The results of
      restriction mapping of the recombinant vector were consistent with those of
      computer analyses. Sequence analysis showed that the cloned gene fragment (518
      bp) had identical sequence with the gene encoding PGRPd of mPGRP-L gene in
      GenBank. The recombinant expression vector pQE-PGRPd was constructed and
      expressed in E. coli M15. SDS-PAGE showed that the expressed product existed
      mainly in the lysate supernatant as a soluble protein with relative molecular
      mass of 29 kD. CONCLUSION: The PGRPd cDNA of mPGRP-L has been successfully cloned
      and expressed in E. coli, which provides the basis for further study of PGRP
      molecule.

PMID- 16624757
TI  - [Sodium transport and its regulation of acutely isolated alveolar type II cells].
AB  - OBJECTIVE: To observe the sodium current of acutely isolated alveolar type II
      cells and its regulation. METHODS: After isolation the AT II cells, the whole
      cell sodium current were recorded in 5 hours with patch-clamp in whole-cell mode,
      and the effect of amiloride and terbutaline on the current was investigated.
      RESULTS: The amiloride-sensitive current of AT II cells were recorded, which
      could be obviously stimulated by terbutaline. CONCLUSION: Acutely isolated AT II
      cells can be valuable for studying electrophysiological characteristics of sodium
      channels even under pathological conditions.

PMID- 16624758
TI  - [In vivo and in vitro anti-tumor effect of Sanjie Kangliu Decoction].
AB  - OBJECTIVE: To study the anti-tumor effect of Sanjie Kangliu (swelling-dispersing)
      Decoction in vivo and in vitro. METHODS: The mice bearing tumors (established by
      subcutaneous inoculation of SRS-82 cells) were fed with Sanjie Kangliu Decoction.
      The tumor was isolated and weighed to calculate the tumor inhibition rate,
      followed by morphological observation of the tumor cells under electron
      microscope. The DNA of the tumor cells was then extracted for agarose gel
      electrophoresis. In the in vitro experiment, cultured SRS-82 cells were treated
      with the serum of rats fed with Sanjie Kangliu Decoction, and the cell viability
      and apoptosis was examined by MTT assay and flow cytometry, respectively.
      Immunocytochemistry was employed to test the expression intensity of Bcl-2
      protein of the rat serum-treated cells, and in situ hybridization performed to
      detect matrix metalloproteinase (MMP)-2 mRNA expression. RESULTS: In the tumor
      bearing mouse models, Sanjie Kangliu Decoction administration resulted in
      significant reduction of the tumor mass and apoptosis of the tumor cells as shown
      by typical apoptotic changes of the cell morphology and presence of DNA ladder in
      agarose gel electrophoresis. In comparison with the mice without the decoction
      treatment, the treated mice showed significantly lower tumor cell viability,
      higher cell apoptosis rate, and weaker Bcl-2 expression. The expression of MMP-2
      mRNA showed no distinct difference between the groups. CONCLUSION: Sanjie Kangliu
      Decoction has obvious anti-tumor effect both in vivo and in vitro possibly
      through the mechanism of inducing tumor cell apoptosis by reducing Bcl-2
      expression without affecting the expression of MMP-2 mRNA.

PMID- 16624759
TI  - [Preparation of small interfering RNA expression cassette based on PCR
      technique].
AB  - OBJECTIVE: To modify the current PCR-based method for rapid and efficient
      preparation of small interfering RNA (siRNA) expression cassette to improve the
      efficiency of RNA interference. METHODS: The U6 promoter sequence was amplified
      by PCR using the genomic DNA of K562 cells as the template, and cloned into pMD18
      T vector which served as the template for further PCR amplification with the
      primers on the plasmid. The amplified product was directly used as the template
      for preparing siRNA expression cassette. The siRNA expression cassette targeting
      p53 gene was amplified, verified by sequencing, and transfected into SH-SY5Y
      cells. After a 48-hour transfection, the cells were harvested and the total RNA
      was for RT-PCR for evaluating the effect of RNA interference. RESULTS: The
      sequencing result confirmed the correct U6 promoter sequence cloned from K562
      cells. After transfection of SH-SY5Y cells for 48 h with siRNA expression
      cassette, the p53 gene expression was inhibited at the mRNA level in comparison
      with the control cells as demonstrated by RT-PCR detection. CONCLUSION: The siRNA
      expression cassette prepared using the established method described hereby can be
      well applicable in RNA interference research.

PMID- 16624760
TI  - [Sleep-disordered breathing and left ventricular remodeling in patients with
      chronic heart failure].
AB  - OBJECTIVE: The investigate the prevalence of sleep-disordered breathing (SDB) and
      evaluate its impact on left ventricular remodeling in adult patients with chronic
      heart failure (CHF). METHODS: Ambulatory sleep recording for 8 h was performed
      using Embletta PDS (Medcare, Iceland) in 74 patients with CHF, and the left
      ventricular ejection fraction (LVEF), internal end-diastolic diameter (LVIDd) and
      left ventricular mass weight (LVMW) were measured using M-mode and two
      dimensional echocardiography. RESULTS: The incidence of SDB defined as an apnea
      hypopnea index (AHI, namely the number of apnea-hypopnea events per hour during
      sleep) no less than 10 was 62.16% in these CHF patients (77.78% in male and
      37.93% in female patients). Of the 74 patients 31.1% had mainly obstructive sleep
      apnea (OSA) and 17.6% had central sleep apnea (CSA). There was a moderate inverse
      correlation between LVEF and AHI (P=0.004, r=-0.366). LVIDd in patients with CHF
      and SDB was significantly greater than that in patients with isolated CHF
      (46.67+/-7.29 vs 55.70+/-11.87 mm, P=0.001). The left ventricular myocardial
      weight was also greater in patients with CHF and SDB than in patients with
      isolated CHF (208.58+/-64.19 vs 291.03+/-121.54, P=0.001). CONCLUSION: Our
      results suggest a higher prevalence of SDB in patients with CHF than in general
      population, and the prevalence is even higher in patients with severe CHF in
      relation to left ventricular remodeling. SDB contributes to the progression of
      CHF and further cardiac decline by a vicious cycle.

PMID- 16624761
TI  - [Automatic decompression with micro-catheter for open and tension pneumothorax].
AB  - OBJECTIVE: To evaluate the feasibility of treating pneumothorax with automatic
      intermittent decompression with micro-catheter instead of traditional thorax
      water sealed drainage (TWSD). METHODS: The automatic decompression instrument
      (ADI), which decompressed intermittently with programmed control, was designed
      and assembled by the authors (Patent No. ZL 01242081.6). A prospective study of
      the efficacy of this device was conducted in 87 pneumatothorax cases, and the
      results were compared with those of TWSD. RESULTS: The average time of closure in
      ADI group was 4.12+/-0.98 days, which was significantly shorter than that with
      TWSD (6.83+/-2.06 days, P<0.01). The incidence of complications was also
      significantly lower in ADI patients (P<0.01), and none of them developed severe
      complications. Clinical cure was achieved in all the patients in ADI group except
      for two patients who gave up treatment voluntarily and one transferred for open
      surgery. CONCLUSIONS: Application of ADI allows faster healing and safer and
      easier operation, and causes fewer complications and less pain with shortened
      hospital stay as compared with conventional therapy for open and tension
      pneumothorax.

PMID- 16624762
TI  - [Intratumor bleomycin-A5 injection under electrolaryngoscope for treatment of
      large laryngopharyngeal and laryngeal hemangioma].
AB  - OBJECTIVE: To study the therapeutic effect of bleomycin-A5 injection under
      eletrolaryngoscope for treatment of large laryngopharyngeal and laryngeal
      hemangioma. METHODS: Intratumor bleomycin-A5 injection under eletrolaryngoscope
      was performed in 18 cases of large laryngopharyngeal and laryngeal hemangioma
      with surface anaesthesia, for totally 7 to 14 (mean 10.2) injections in each
      case. RESULTS: Twelve patients were cured and 6 showed obvious improvement.
      Follow-up of the patients for over one year found no recurrence of the
      hemangioma. CONCLUSION: Bleomycin-A5 injection is a minimal invasive procedure
      for treatment of large laryngopharyngeal and laryngeal hemangioma, causing less
      pain and better preserving the laryngeal function without the necessity of
      tracheotomy.

PMID- 16624763
TI  - [Analysis of auditory steady-state response to multiple simultaneous stimuli and
      cochlea morphology in guinea pigs with posterior semicircular canal fistula].
AB  - OBJECTIVE: To observe the changes of auditory steady-state response (ASSR)
      threshold in guinea pigs with posterior semicircular canal fistula. METHODS: In
      10 guinea pigs, a window was opened in the posterior semicircular canal of the
      left ear with the right ear serving as the control for testing the ASSR under
      anesthesia with pentobarbital sodium. RESULTS: The mean and standard deviation of
      ASSR threshold (dB SPL) at 0.5, 1, 2, and 4 kHz in the left ear was 35.00+/
      14.33, 25.50+/-12.37, 20.00+/-9.37 and 20.00+/-9.18, respectively, and was
      31.00+/-16.19, 25.50+/-12.34, 18.00+/-6.96 and 18.50+/-6.71 in the right ear,
      respectively. Paired-sample t test showed no significant difference in the ASSR
      at the same frequency between the two ears. CONCLUSION: Small fistula by surgery
      causes no significant hearing loss in guinea pigs.

PMID- 16624764
TI  - [Thoughts on modern aphasic discourse studies].
AB  - This article gives a brief introduction to the content of aphasic discourse
      analysis, the theoretical frameworks applied, and critical findings . It also
      points out the problem that faces the study, the variety of study methods that
      arises, and the future trend. The structuralists tend to focus on the micro
      aspects of the discourse while the functionalists on its general structure and
      the meaning. The study in the future shall address the connection of these two
      levels.

PMID- 16624765
TI  - [Effect of intralipid for ameliorating protein loss in severe burned patients].
AB  - OBJECTIVE: To investigate the effect of intralipid on protein consumption in
      severe burned patients. METHODS; Sixty-seven nonoperative patients with severe
      burns were divided into Intralipid treatment group and non-intralipid treatment
      group (control group), and the former was treated with 20% intralipid (500 ml
      once a day) from postburn day 4 for 10 consecutive days. Venous blood samples
      were collected from these patients for testing total protein, albumin, total
      cholesterol and triglyceride on postburn days 1, 7 and 14, respectively. RESULTS:
      The levels of total protein, albumin, total cholesterol and triglyceride were
      within normal range on postburn day 1 in both groups, and only the albumin level
      was lowered in the groups on day 7 but at comparable magnitudes (32+/-4.83 vs
      31+/-5.04 g/L, P<0.05). In contrast, the levels of total protein, albumin, total
      cholesterol and triglyceride were below the normal range on postburn day 14 in
      both groups, but intralipid treatment group showed more albumin loss than the
      control group (28+/-6.46 vs 23+/-7.03 g/L, P<0.01). CONCLUSION: Intralipid (20%)
      provides good energy source to ameliorate albumin loss in severe burned patients.

PMID- 16624766
TI  - [Effects of small fenestra stapedotomy in comparison with total stapedectomy].
AB  - OBJECTIVE: To compare the effect of small fenestra stapedotomy and total
      stapedectomy in patients with otosclerosis. METHODS: Twenty-seven patients (30
      ears) undergoing small fenestra stapedotomy and 36 patients (43 ears) receiving
      total stapedectomy were compared for hearing results and complication rates.
      RESULTS: No statistically significant differences were seen in postoperative
      speech pure tone average in closing air-bone gap between the two groups. The ears
      treated by small fenestra stapedotomy showed statistically better air-bone gap
      closure at high frequencies with lower rates of sensorineural hearing loss at
      high frequencies and milder dizziness. CONCLUSION: In spite of the successful
      hearing outcomes in both groups, small fenestra stapedotomy can achieve better
      results at high frequencies and reduce the incidence of complications.

PMID- 16624767
TI  - [Expression of vascular endothelial growth factor in human placental trophoblasts
      and angiogenesis in the chorionic villi].
AB  - OBJECTIVE: To investigate the expression of vascular endothelial growth factor
      (VEGF) in human placental trophoblasts and the role of VEGF in regulating
      placental villous angiogenesis. METHODS: Placental samples were obtained from 10
      pregnant women receiving induced abortion in the first trimester, 10 receiving
      induced labor in the second trimester and 10 having cesarean section at term
      delivery, with gestational duration of 6-9, 18-22 and 37-38 weeks, respectively.
      All the samples were fixed in formalin solution and prepared for the
      morphological study. The expression of VEGF and vascular distribution in the
      placental villi were examined and evaluated by immunohistochemistry and
      stereomorphometry, respectively. RESULTS: In the course of pregnancy, there was a
      significant decrease in the level of VEGF expression in chorionic villi (28.19+/
      3.01, 18.65+/-2.43, 4.95+/-0.86, respectively, P<0.01). The radial parameters of
      the blood vessels showed no significant changes (26.67+/-7.74, 25.08+/-4.67,
      23.36+/-5.30, respectively, P>0.05), but the length density of the blood vessels
      increased significantly (1.46+/-0.64, 5.58+/-1.31, 19.56+/-1.40, respectively,
      P<0.01). CONCLUSION: During gestation, VEGF expression in chorionic villi
      gradually weakens but the length density of the blood vessels increases,
      indicating that VEGF is not the only regulatory factor of angiogenesis in the
      chorionic villi.

PMID- 16624768
TI  - [Mechanical periodontal treatment combined with tetracycline for aggressive
      periodontitis].
AB  - OBJECTIVE: To evaluate the effect of mechanical periodontal treatment combined
      with tetracycline on periodontal attachment, distances of cementum-enamel
      junction (CEJ) to the bone defect bottom and to the alveolar crest, and avidity
      of serum IgG against Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) in
      patients with aggressive periodontitis. METHODS: Twenty-six patients with
      aggressive periodontitis were divided equally into two groups to receive
      mechanical periodontal treatment combined with tetracycline or exclusive
      mechanical periodontal treatment, with another 20 periodontally healthy subjects
      serving as the control group. In the two patient groups, routine clinical
      examination of the subjects was performed to record periodontal attachment level
      and distances of CEJ to the bottom of the bone defects and to the alveolar crest
      before and 3 and 6 months after the treatment. The avidity of serum IgG against
      Pg LPS was measured by ELISA with thiocyanate elution before and after
      periodontal treatment. RESULTS: Compared with patients with exclusive mechanical
      periodontal treatment, patients with combined treatments showed significant
      improvement in periodontal attachment level and the distance of CEJ to the bone
      defect bottom after the treatment (P<0.01 and P<0.05, respectively) with also
      significantly reduced avidity of serum IgG against Pg LPS (P<0.01). CONCLUSION:
      Mechanical periodontal treatment combined with tetracycline produces favorable
      effects in patients with aggressive periodontitis.

PMID- 16624769
TI  - [Effect of vitamin B12 mixed solution inhalation for acute radiation-induced
      mucosal injury].
AB  - OBJECTIVE: To evaluate the therapeutic effect of inhalation of vitamin B12 mixed
      solution in treating acute radiation-induced mucosal injury. METHODS: Totally 122
      patients with acute radiation-induced mucosal injury resulting from radiotherapy
      were divided into two equal groups and received vitamin B12 mixed solution
      inhalation and gentamycin sulfate mixed solution inhalation, respectively.
      RESULTS: The patients receiving inhalation of vitamin B12 mixed solution showed
      favorable response to the treatment and the mucosal injury was alleviated as
      manifested by relieved pains, improved appetite and lessened body weight loss,
      which allowed uninterrupted administration of radiotherapy. In patients treated
      with inhalation of gentamycin sulfate mixed solution, by contrast, the mucosal
      injury was serious and in 8 patients radiotherapy had to be suspended for acute
      radiation-induced mucosal injury. CONCLUSION: Vitamin B12 mixed solution
      inhalation can be an effective treatment for acute radiation-induced mucosal
      injury.

PMID- 16624770
TI  - [Preparation and electron microscopic observation of lidocaine microemulsion].
AB  - OBJECTIVE: To prepare and determine the proportion of the components of lidocaine
      microemulsion. METHODS: Pseudoternary phase diagrams of the prepared lidocaine
      microemulsion with different Km (surfactant/cosurfactant) were generated to
      determine the optimal Km according to the size of the microemulsion area. The
      diameter and its distribution range, viscosity, electric conductivity and
      refractivity of lidocaine microemulsion drop was determined, and the appearance
      and system type of the microemulsion was observed using electron microscope.
      RESULTS; Maximum microemulsion area in the pseudoternary phase diagrams was
      obtained with the Km of 3, and the drop size of the microemulsion averaged 29.8+/
      14.4 nm (with up to 98% of the drop size ranging between 15.1-45.5 nm and 2%
      between 77.9-261.3 nm). At 25 degrees C, the viscosity, electric conductivity and
      refractivity of the microemulsion was 25 mPa.S, 130 micros/cm and 1.473,
      respectively, and the lidocaine microemulsion was identified to belong to O/W
      type. The microemulsion drop appeared in spherical shape of heterogeneous sizes
      in a multi-disperse system. CONCLUSION: The optimal proportion of the components
      in lidocaine microemulsion can be obtained by analyzing pseudoternary phase
      diagrams, and the drop size, distribution, shape and system type can be
      determined or observed through Maerwen Zetasizer combined with electron
      microscopic observation.

PMID- 16624771
TI  - [Analysis of factors for bacterial infection following liver transplantation].
AB  - OBJECTIVE: To investigate the association of surgical skills, anhepatic time and
      preoperative hepatic function grading with bacteria infection after the liver
      transplantation and identify the common bacterial flora involved for effective
      prevention and treatment of the posttransplant bacterial infection. METHODS;The
      clinical records of 31 cases of liver transplantation from August 2004 to August
      2005 were reviewed and the collected data were analyzed statistically. RESULTS;
      Among the 31 cases, posttransplant bacterial infection occurred in 16 cases
      accounting for a total incidence of 51.61%, with the incidence of multi-system
      (or multi-organ) infection of 22.58%. The earlier cases had longer average
      surgery time and anhepatic period than the later cases, with also higher
      incidence of infection. Among the 19 patients with hepatic function class A
      before surgery, 7 acquired bacterial infection involving one system or organ, 2
      had infections compromising multiple system or organ. In the 8 patients of
      hepatic function class B before surgery, 2 had single-system or -organ infection
      and 1 multi-system or -organ infection. Four out of the 5 patients with hepatic
      function class C before surgery acquired posttransplant bacterial infections, all
      involving multiple systems or organs. Pseudomonas aeruginosa was the most common
      bacteria responsible for the infections in these cases. CONCLUSION: Improvement
      of surgical skills can obviously reduce the incidence of bacterial infection
      after liver transplantation. No evidences suggest the correlation between the
      incidence of infections (including severe ones) and hepatic function class A or B
      before the operation, whereas patients with preoperative hepatic function class C
      seems to be at higher risk for infection involving multiple systems or organs.
      The anhepatic time does not significantly impact on the incidence or severity of
      the posttransplant infections, and Pseudomonas aeruginosa is the most common
      bacteria causing the infections.

PMID- 16624772
TI  - [Effect of oral cordarone in reversing persistent atrial fibrillation].
AB  - OBJECTIVE: To observe the efficacy and safety of oral cordarone dir reversing
      persistent atrial fibrillation (AF). METHODS; Eighty-two symptomatic chronic AF
      out-patients without history of acute diseases or severe hepatic/thyroid
      dysfunction were given oral cordarone at the loading dose of 200 mg thrice a day
      for 1-4 weeks followed by a twice-daily administration for another 1-4 weeks,
      with the maintenance dose of 200 or 100 mg once a day. The incidence of stroke
      and cardiac events and the mortality rate were compared between 43 patients with
      restored rhythm on cordarone and 39 patients on digoxin and/or betaloc for
      ventricular rhythm control. RESULTS: Among the 82 patients, sinus rhythm
      restoration was achieved in 43, with a successful rate of 52%. In 18 patients,
      the ejection fraction increased from (32+/-8)% to (46+/-10)%, left atrium
      diameter decreased from (4.6+/-1.1) cm to (4.1+/-0.8) cm. Except for slight T4
      increase, QT prolongation and bradycardia in 3 cases, severe side effects were
      not observed in this study. Only one patient with restored sinus rhythm required
      rehospitalization after half a year for worsened heart failure, but in patients
      with controlled ventricular rhythm, 1 developed stroke, 1 experienced heart
      attack and 1 died of heart failure with bleeding. CONCLUSION: For patients with
      symptomatic reversible persistent AF, active treatment with cordarone can be
      convenient, effective and safe for sinus rhythm restoration.

PMID- 16624773
TI  - [Effect of perioperative continuous epidural morphine administration on plasma D
      dimer in patients undergoing total hip replacement].
AB  - OBJECTIVE: To evaluate the effect of perioperative continuous epidural morphine
      administration on plasma D-dimer level in patients undergoing total hip
      replacement. METHODS: Forty ASA I-II patients undergoing total hip replacement
      under epidural anesthesia were randomized into two groups. In one group, the
      patients were given epidural administration of morphine 15 min before operation
      at 4 mg (in 10 ml normal saline) and for 48 h after the operation at 80 microg/h,
      while those in the other group received epidural injection of the same amount of
      normal saline before operation and 0.15% ropivacaine 2.0 ml/h for 48 h in the
      same manner after operation. Blood samples were taken before anesthesia (T(0)),
      at the end of operation (T(1)), and 24 h and 48 h after operation (T(2) and T(3))
      for determination of plasma IL-6 and D-dimer levels. RESULTS: In both groups
      plasma IL-6 and D-dimer levels showed significant increase at T(1), T(2) and T(3)
      in comparison with those at T(0), and their levels were significantly lower in
      morphine group than in ropivacaine group at T(1), T(2) and T(3). CONCLUSION:
      Epidural morphine can lower plasma IL-6 and D-dimer levels and correct blood
      hypercoagulability in patients undergoing total hip replacement.

PMID- 16624774
TI  - [Effect of Shenkangwan on mesangial cell NO and TGF-beta1 excretion in rats with
      early diabetic nephropathy].
AB  - OBJECTIVE: To study the mechanism of Shenkangwan (SKW) in treating early diabetic
      nephropathy (DN). METHODS: The effect of SKW on NO and transforming growth factor
      (TGF)-beta(1) production by the mesangial cells (MCs) of rats with early diabetic
      nephropathy was evaluated with serum pharmacological method. RESULTS: Compared
      with normal serum, the SKW-containing serum dose- and time-dependently inhibited
      TGF-beta(1) excretion and increased NO production in the MCs of rats with early
      DN (P<0.05 and P<0.01, respectively). CONCLUSION: The therapeutic effect of SKW
      on early DN may rely on the balance modulation of cytokine network by increasing
      NO production and decreasing TGF-beta(1) excretion to prevent cytokine-induced
      damage of the MCs.

PMID- 16624775
TI  - [Effects of ossicular reconstruction with partial ossicular replacement
      prosthesis in patients with tympanosclerosis].
AB  - OBJECTIVE: To evaluate the effect of ossicular reconstruction with partial
      ossicular replacement prosthesis (PORP) in patients with tympanosclerosis.
      METHODS: The data of 28 cases of tympanosclerosis treated between 1992 and 2006
      were reviewed. Of the 28 patients, 14 (14 ears) underwent ossicular
      reconstruction with PORP and 14 (14 ears) had ossicular mobilization, and all the
      patients were followed-up for 3-24 months. RESULTS: Significant improvement was
      found in postoperative speech frequency (500, 1000, 2000 Hz) pure tone average
      (PTA) and air-bone gap (ABG) closure after in the operation the two groups.
      Ossicular reconstruction using PORP resulted in statistically better ABG closure
      and PTA (P<0.05). CONCLUSION: In ossicular attic fixation, ossicular
      reconstruction using PORP can yield better results than mobilization of the major
      ossicles in patients with tympanosclerosis.

PMID- 16624776
TI  - [Effect of estrogen on osteoprotegerin, osteoclast differentiation factor and
      macrophage colony stimulating factor mRNA expressions in ovariectomized rat bone
      tissue].
AB  - OBJECTIVE: To observe the effect of the estrogen on the mRNA expression of
      osteoprotegerin (OPG), osteoclast differentiation factor (ODF) and macrophage
      colony stimulating factor (M-CSF) in bone tissue of ovariectomized rats, and
      investigate the possible pathway of estrogen in preventing and treating
      postmenopausal osteoporosis. METHODS; Thirty healthy adult SD rats were randomly
      divided into sham operation group, ovariectomized group and estrogen-treated
      group. All rats were ovariectomized except those in the sham operation group.
      Bone density of the L3-L6 vertebra was detected 12 weeks after the operation. The
      total RNA were extracted from the femur to examine mRNA expression of OPG, ODF
      and M-CSF by real-time PCR. RESULTS: Estrogen increased the bone density of the
      ovariectomized rat lumbar vertebra and up-regulated the expression of OPG,
      whereas down-regulated the expression of M-CSF and lowered ODF:OPG ratio.
      CONCLUSION: The effect of estrogen in treating postmenopausal osteoporosis is
      closely correlated with the regulation of OPG and M-CSF expressions and ODF:OPG
      ratio.

PMID- 16624777
TI  - [Learning curve of laparoscopic resection for rectal cancer].
AB  - OBJECTIVE: To evaluate the surgical outcomes of laparoscopic resection for rectal
      cancer and to investigate how surgeons without previous training of laparoscopic
      cholecystectomy(LC) can quickly learn laparoscopic resection for rectal cancer.
      METHODS: Clinical data of 105 cases of laparoscopic rectal resection performed by
      a group of surgeons without previous training of LC were reviewed. The cases were
      divided equally into 3 groups (groups A, B and C) according to the sequence of
      the operations. The operating time, blood loss, lymph node harvest, length of
      specimen, conversion rate to open surgery, intra- and postoperative complications
      and hospital stay were compared between the 3 groups. RESULTS: There were no
      significant differences between the 3 groups with respect to age, gender,
      Dukes'stage or surgical approach (P>0.05). The operating time in group A was
      196.1+/-30.3 min, significantly longer than that in group B (164.8+/-22.7 min)
      and group C (158.7+/-20.9 min) (P<0.001), but the operating time did not vary
      significantly between groups B and C (P>0.05). The blood loss was significantly
      greater in group A than in groups B and C (72.4+/-21.5, 48.2+/-16.3, and 46.6+/
      15.4 ml, respectively, P<0.001), but showed no significant difference between the
      latter two groups (P>0.05). The rate of conversion to open surgery decreased from
      11.4% in group A to 2.9% in group B and group C, but the difference was not
      statistically significant (P>0.05). The rate of intraoperative complications
      declined from 17.1% in group A to 5.7% in group B and group C, showing no
      significant difference either. The lymph node harvest, length of specimen, and
      postoperative complications showed no significant variation between the 3 groups
      (P>0.05), but group C had significantly shorter mean hospital stay in comparison
      with groups A and B (P<0.001). The 35 patients in group A received the operation
      within a time period of 17 months (2.1 cases per month), and operations in groups
      B and C were done in 7 months (5 cases per month). CONCLUSION: The learning curve
      of laparoscopic rectal resections is approximately 35 cases, and the surgeons
      without previous experience of laparoscopic cholecystectomy can learn the
      surgical skills after performing 35 laparoscopic resections for rectal cancer at
      the monthly frequency of 2.1 cases.

PMID- 16624778
TI  - Correlations between regional brain volumes and memory performance in anoxia.
AB  - This study was aimed at investigating the quantitative relationship between
      regional brain volumes (hippocampus, amygdala, as well as cerebrum, frontal lobe,
      parietal lobe, temporal lobe) and performance on anterograde and retrograde
      memory tests in anoxic patients. We used high-resolution MRI to measure brain
      volumes in 13 anoxic patients. Neuropsychological testing was conducted
      contemporaneously with MRI. To control for age and sex, neuroanatomical volume
      residuals were calculated using regression equations derived from a group of 87
      healthy comparison participants. We found that anoxic patients with severe
      amnesia had hippocampal volumes that were 36% smaller than normal, whereas
      patients with mild or no amnesia had normal hippocampal volumes. Regional gray
      matter volumes in severe amnesic anoxics were substantially smaller than
      expected. Performances on anterograde memory tests were significantly correlated
      with hippocampal and regional gray matter volume residuals. There was a
      significant correlation between white matter volume (but not hippocampal volume)
      and performance on the Visual Retention Test, a multi-dimensional test of
      cognitive function. There were no significant correlations between
      neuroanatomical measures and performance on a retrograde memory test. Our results
      indicate a strong quantitative relationship between performance on anterograde
      memory tests and hippocampal and regional gray matter volume residuals.
      Correlations between white matter volume residuals and performance on the VRT
      were found to be independent of hippocampal volume. Given the strong correlation
      between hippocampal volume and total gray matter volume residuals, a
      quantitative, normalized measure of total gray matter volume may provide a good
      indication of clinical outcome in anoxia.

PMID- 16624779
TI  - Attention and memory evaluation across the life span: heterogeneous effects of
      age and education.
AB  - The developmental sequences of attention and memory were studied by utilizing
      normative data derived from the neuropsychological battery named NEUROPSI
      ATTENTION AND MEMORY. A sample of 521 Spanish-speaking individuals, aged 6 to 85
      years, participated in this study. In the adult sample, educational level ranged
      from 0 to 22 years of education. Data from subtests measuring orientation,
      attention and concentration, executive functions, working memory, immediate and
      delayed verbal memory, and immediate and delayed visual memory were included. The
      factor structure of the analyzed battery is presented. The effects of age and
      education on this structure were analyzed. Results suggested that although
      attention and memory are related, their developmental sequences are separated
      from one another. During childhood, the development of selective and sustained
      attention, attentional-working memory, and executive functions showed a fast
      improvement in performance. Development of verbal memory and place and person
      orientation showed a slower increment in scores. In the adult sample it was found
      that factors related to memory are sensitive to age, whereas those related to
      attention and executive functions are sensitive to education. The consideration
      of both the developmental sequence, as well as differential effects of education,
      can improve the sensitivity and specificity of neuropsychological measures,
      allowing early diagnosis of cognitive dysfunction and implementation of adequate
      rehabilitation programs.

PMID- 16624780
TI  - "Vascular depression" predicts verbal fluency in older adults.
AB  - Past research has found links among cerebrovascular risk factors (CVRFs),
      depression, and cognition in older adults. This study investigated how well
      baseline cerebrovascular burden and depression predicted verbal fluency three and
      six months later. Participants were 139 medical rehabilitation patients, age 60
      and above. The Geriatric Depression Scale, Charlson Co-Morbidity Index, and
      Dementia Rating Scale were administered at baseline, and verbal fluency was
      measured three and six months later. Structural equation modeling found that
      depression significantly predicted verbal fluency at both time points,
      independently of demographic variables, baseline cognition, or medical burden.
      CVRFs correlated with depressive symptoms but did not independently predict
      verbal fluency. Findings suggest that vascular depression may be a possible
      signal of impaired brain integrity, consistent with Alexopoulos and colleague's
      (2000) conceptual framework.

PMID- 16624781
TI  - Word and face recognition in children with congenital hypothyroidism: an event
      related potential study.
AB  - The repetition paradigm offers a useful technique for assessing recognition
      memory by evaluating how an individual responds to new versus old stimuli. While
      this paradigm has been extensively used in adults with and without clinical
      conditions, it has not, to our knowledge, been studied in a clinical pediatric
      population. Children with congenital hypothyroidism (CH) identified by newborn
      screening and treated early in life have normal intelligence but demonstrate
      residual cognitive deficits including selective memory problems that are
      attributed to their loss of thyroid hormone during hippocampal formation. Since
      the hippocampus is integral for recognition memory, we hypothesized that children
      with CH would perform atypically on the repetition paradigm. Event-related
      potentials (ERPs) were recorded during word and face recognition in nine children
      aged 11 to 13 years with CH and nine typically developing children matched for
      age. Results revealed that while the groups did not differ in accuracy or
      reaction time, they did differ significantly on selective ERP components. Like
      normal adults, the comparison children showed a positive elevation in P3
      amplitude for repeated relative to new words at the parietal electrodes, whereas
      children with CH did not. Both groups produced weak repetition effects when
      viewing faces, although the amplitudes of children with CH were somewhat smaller.
      It is proposed that the dampened neurophysiological response to repeated verbal
      stimuli by children with CH may explain some of their clinically observed
      difficulties in short-term recognition memory.

PMID- 16624782
TI  - Working-delayed memory difference detects mild cognitive impairment without being
      affected by age and education.
AB  - Performance on neuropsychological tests is affected by age and education, which
      makes the early detection of cognitive impairment difficult when assessing
      individuals of varying levels of education. We examined the effects of age,
      education, and gender on three memory indexes of the Wechsler Memory Scale-III,
      Delayed Memory, Working Memory and the difference between Working-Delayed Memory
      in a sample of patients with amnestic Mild Cognitive Impairment, patients with
      mild probable Alzheimer's disease, and a nondemented elderly comparison group.
      Whereas Delayed and Working Memory scores were affected by participant type, age,
      and education, the Working-Delayed Memory difference score was affected by
      participant type, only. Our preliminary conclusions, pending replication of the
      findings with a larger sample, are that working-delayed memory difference was
      sensitive to early memory decline without being affected by age and education.

PMID- 16624783
TI  - Semantic verbal fluency in Alzheimer's disease: approaches beyond the traditional
      scoring system.
AB  - This study aimed to expand extant Alzheimer's disease (AD) research on cluster
      size and switching strategies in semantic verbal fluency (SVF). First, it
      addressed a significant shortcoming in research, that is, the use of a single
      semantic category (i.e., Animal). Second, it examined subjects of lower education
      levels, as research to date has primarily focussed on tertiary education.
      Subjects were 26 mild to moderate AD patients and 26 healthy elderly, 65 years
      old and over, with less than 12 years of schooling. The study examined the
      cluster size and switching variables, together with the number of subcategories,
      in two semantic categories (i.e., Animal and Supermarket). Furthermore, it
      investigated the error patterns (i.e., repetitions and categorical errors) across
      three semantic categories (i.e., Animal, Supermarket and Furniture). The findings
      provide preliminary support for category-specific effects on qualitative aspects
      of SVF highlighting the need to incorporate multiple semantic categories to
      research and clinical practice.

PMID- 16624784
TI  - Functional outcome in TBI I: neuropsychological, emotional, and behavioral
      mediators.
AB  - Literature exists to suggest that the severity of traumatic brain injury (TBI) is
      positively associated with the severity of functional impairment. However,
      potential mediators of this relationship have not been studied systematically. In
      the present study, we evaluated a model hypothesized to explain the relationship
      between TBI severity and functional impairment in 87 patients with moderate-to
      severe TBI, studied longitudinally. Using structural equation modeling, we found
      that only neuropsychological status (but not emotional or behavioral
      difficulties) consistently mediated the relationship between TBI severity and
      functional outcome at 12-months post-injury. These findings suggest that, of the
      factors examined here, neurocognitive compromise plays the most prominent role in
      mediating post-TBI adaptive functioning in moderate-to-severe TBI, which has
      important implications for post-injury interventions.

PMID- 16624785
TI  - Functional outcome in TBI II: verbal memory and information processing speed
      mediators.
AB  - Following traumatic brain injury (TBI), patients often report memory
      difficulties, as well as reduced information processing speed. However, it
      remains unclear the extent to which these deficits contribute to functional
      impairment. In the present study, we compared the relative contribution of verbal
      memory and information processing speed to functional impairment at 12-month post
      injury, in 87 patients with moderate-to-severe TBI. Employing structural equation
      modeling, we found that information processing speed, but not verbal memory
      functions, significantly mediated the relationship between TBI severity and post
      TBI adaptive functioning. These findings suggest that despite the pervasive
      memory complaints among patients with TBI, it is the impact of neurotrauma on
      frontal systems that appears to be primarily responsible for patients'
      difficulties in social and occupational functioning.

PMID- 16624786
TI  - Application of new WAIS-III/WMS-III discrepancy scores for evaluating memory
      functioning: relationship between intellectual and memory ability.
AB  - Analysis of the discrepancy between memory and intellectual ability has received
      some support as a means for evaluating memory impairment. Recently, comprehensive
      base rate tables for General Ability Index (GAI) minus memory discrepancy scores
      (i.e., GAI-memory) were developed using the WAIS-III/WMS-III standardization
      sample (Lange, Chelune, & Tulsky, in press). The purpose of this study was to
      evaluate the clinical utility of GAI-memory discrepancy scores to identify memory
      impairment in 34 patients with Alzheimer's type dementia (DAT) versus a sample of
      34 demographically matched healthy participants. On average, patients with DAT
      obtained significantly lower scores on all WAIS-III and WMS-III indexes and had
      larger GAI-memory discrepancy scores. Clinical outcome analyses revealed that GAI
      memory scores were useful at identifying memory impairment in patients with DAT
      versus matched healthy participants. However, GAI-memory discrepancy scores
      failed to provide unique interpretive information beyond that which is gained
      from the memory indexes alone. Implications and future research directions are
      discussed.

PMID- 16624787
TI  - The contribution of a cognitive bias against disconfirmatory evidence (BADE) to
      delusions in schizophrenia.
AB  - A neuropsychological paradigm is introduced that provides a measure of a bias
      against disconfirmatory evidence (BADE), and its correspondence with delusions in
      people with schizophrenia and schizoaffective disorder was investigated. Fifty
      two patients diagnosed with schizophrenia or schizoaffective disorder (36 were
      acutely delusional) and 24 healthy control participants were presented with
      delusion-neutral pictures in each trial, and were asked to rate the plausibility
      of four written interpretations of the scenario depicted by that picture.
      Subsequently, new pictures that provided background information about the
      depicted scenario were successively presented, and participants were requested to
      adjust their ratings, taking into account this new information. Two of the
      interpretations appeared tenable initially but ultimately proved to be
      implausible, one appeared untenable initially but eventually proved to be
      plausible, and one appeared untenable at all stages. A BADE was observed for
      delusional compared to non-delusional patients, as well as for all patients
      compared to controls. In addition, regardless of symptom profile, patients were
      more accepting of implausible interpretations than controls. The present work
      suggests that deficits in reasoning may contribute to the maintenance of
      delusions via an impairment in the processing of disconfirmatory evidence.

PMID- 16624788
TI  - Metamemory monitoring and Parkinson's disease.
AB  - Feeling-of-knowing (FOK) and global prediction in episodic memory were examined
      in 16 patients with Parkinson's disease (PD) and 16 elderly control subjects.
      Subjects were given cued recall and recognition tests of 20 critical cue-target
      words. Prior to the study phase, participants were asked to predict the number of
      words they could recall. During the recall phase, they judged their FOK for non
      recalled words in terms of how likely they thought they would be able to
      recognize the key words on a subsequent recognition test. No difference was found
      in the two groups for global prediction accuracy. However in comparison to the
      older adults, PD patients exhibit impaired FOK accuracy, suggesting that in some
      circumstances metamemory may be altered in Parkinson's disease.

PMID- 16624789
TI  - Mad cows and the maddening decade of public health.

PMID- 16624790
TI  - Can fear arousal in public health campaigns contribute to the decline of HIV
      prevalence?
AB  - Most American health professionals who work in HIV/AIDS do not support the use of
      fear arousal in AIDS preventive education, believing it to be counterproductive.
      Meanwhile, many Africans, whether laypersons, health professionals, or
      politicians, seem to believe there is a legitimate role for fear arousal in
      changing sexual behavior. This African view is the one more supported by the
      empirical evidence, which suggests that the use of fear arousal in public health
      campaigns often works in promoting behavior change, when combined with self
      efficacy. The authors provide overviews of the prevailing American expert view,
      African national views, and the most recent findings on the use of fear arousal
      in behavior change campaigns. Their analysis suggests that American, post-sexual
      revolution values and beliefs may underlie rejection of fear arousal strategies,
      whereas a pragmatic realism based on personal experience underlies Africans'
      acceptance of and use of the same strategies in AIDS prevention campaigns.

PMID- 16624791
TI  - Just inducing fear of HIV/AIDS is not just.

PMID- 16624792
TI  - Can fear arousal in public health campaigns contribute to the decline of HIV
      prevalence?

PMID- 16624793
TI  - The controversy over fear arousal in AIDS prevention and lessons from Uganda.

PMID- 16624794
TI  - Sensation seeking and alcohol use by college students: examining multiple
      pathways of effects.
AB  - This study tests the proposition that peer influence mediates the effect of
      sensation seeking, a personality trait, on alcohol use among college students.
      Cross-sectional data to test this proposition were collected from a
      representative sample of college students at a large public northeastern
      university (N = 427). Results of hierarchical regression analyses showed that, as
      hypothesized, sensation seeking influenced personal alcohol use both directly and
      indirectly, through its impact on students' frequency of association with alcohol
      using peers and the size of their drinking norm misperception. The findings
      suggest that interventions that seek to limit the frequency in which high
      sensation seekers associate with peers whose alcohol use is extreme or,
      alternatively, seek to facilitate social interactions of high sensation seekers
      with normative peers, may supplement efforts to influence sensation seekers'
      alcohol and other drug use through tailored mass media advertisements.

PMID- 16624795
TI  - Mediators and moderators of magazine advertisement effects on adolescent
      cigarette smoking.
AB  - The purpose of the present study is to examine the relation between magazine
      advertising for cigarettes and adolescent cigarette smoking. Participants (242
      adolescents) reported their frequency of reading 46 magazines and their attention
      to cigarette ads. Recognition of cigarette ads, passive peer pressure (i.e.,
      normative beliefs), and the smoker image also were assessed. Results indicate
      that exposure to cigarette advertising and recognition of ads augment the effect
      of passive peer pressure on smoking. In addition, a positive smoker image was
      associated with attention to advertising and mediated the relation between
      attention and smoking. It is suggested that the effect of magazine ads on
      adolescents should be considered in policymaking on cigarette advertising.

PMID- 16624796
TI  - Impact of an entertainment-education television drama on health knowledge and
      behavior in Bangladesh: an application of propensity score matching.
AB  - Shabuj Chaya is a weekly television drama broadcast during a 13-week period in
      Bangladesh in 2000. It used an entertainment-education format to increase health
      knowledge and to promote visits to health clinic and modern contraceptive use.
      The purpose of this article is to demonstrate how a relatively new statistical
      technique, propensity score matching in conjunction with structural equation
      modeling, can be used to obtain an unbiased estimate of changes in health
      outcomes that can be attributed to exposure to the drama. The analysis is
      conducted with data from an after-only, cross-sectional survey of 4,492 men and
      women from the intended audience. The results from propensity score matching
      approximate what would be expected from a randomized control group design.

PMID- 16624797
TI  - Quality of life: questionnaires and questions.
AB  - Quality of life (QoL) is a phrase often used in health care settings at policy
      and administration levels, in clinical assessments of therapies, and in clinical
      management of individual cases. While QoL is a broad concept that covers such
      areas as social, environmental, economic, and health satisfaction, health-related
      quality of life (HRQL) is less wide ranging, including mental and physical health
      and their consequences. First, I question the singularity of HRQL, suggesting
      there are at least two distinct meanings of HRQL. Second, questionnaires designed
      to assess individual patients' HRQL allow a limited range of ways for patients to
      express their state of being. The Medical Outcomes Study Short Form (SF-36),
      which operationalises HRQL for a traditional clinical setting, is used to show in
      detail the restricted options that are available for patient respondents. The
      communications limitations of utility-based measures, designed as cost
      effectiveness measures but often used as though they were HRQL instruments, are
      also discussed. For assessing the HRQL of individuals in a health setting, such
      questionnaires can provide only a starting point, which should be supplemented
      with good interaction and communication.

PMID- 16624798
TI  - The health buck stops where? Thematic framing of health discourse to understand
      the context for CVD prevention.
AB  - Using a constructed week methodology, we analyzed media summaries for the type of
      health discourse (health care delivery, disease-specific prevention, lifestyle
      risk factors, public/environmental health disease, social determinants of health)
      portrayed over a 5-year period as a means of describing the context within which
      health staff worked to prevent heart disease in one Canadian province. The
      results reveal that heart disease received very little media coverage, despite
      provincial health data revealing it to be the leading cause of mortality,
      morbidity, and health care costs. Coverage of the health care system dominated
      the media landscape over the 5-year period. The study findings also suggest that
      the health discourses in the media summaries were represented as primarily
      thematic, rather than as episodic narratives, relieving any one level of
      government as entirely responsible for the health of its constituents. Media
      advocacy strategies may be a means to redress the imbalance of health discourses
      presented by the media.

PMID- 16624800
TI  - A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical
      cancer cells antagonizes the full-length P2X7 receptor through hetero
      oligomerization.
AB  - A truncated naturally occurring variant of the human receptor P2X7 was identified
      in cancer cervical cells. The novel protein (P2X7-j), a polypeptide of 258 amino
      acids, lacks the entire intracellular carboxyl terminus, the second transmembrane
      domain, and the distal third of the extracellular loop of the full-length P2X7
      receptor. The P2X7-j was expressed in the plasma membrane; it showed diminished
      ligand-binding and channel function capacities and failed to form pores and
      mediate apoptosis in response to treatment with the P2X7 receptor agonist benzoyl
      ATP. The P2X7-j interacted with the full-length P2X7 in a manner suggesting
      heterooligomerization and blocked the P2X7-mediated actions. Interestingly, P2X7
      j immunoreactivity and mRNA expression were similar in lysates of human cancer
      and normal cervical tissues, but full-length P2X7 immunoreactivity and mRNA
      expression were higher in normal than in cancer tissues, and cancer tissues
      lacked 205-kDa P2X7 immunoreactivity suggesting lack of P2X7 homo(tri)
      oligomerization. These results identify a novel P2X7 variant with apoptosis
      inhibitory actions, and demonstrate a distinct regulatory property for a
      truncated variant to antagonize its full-length counterpart through hetero
      oligomerization. This may represent a general paradigm for regulation of a
      protein function by its variant.

PMID- 16624801
TI  - Characterization of the exchangeable protons in the immediate vicinity of the
      semiquinone radical at the QH site of the cytochrome bo3 from Escherichia coli.
AB  - The cytochrome bo3 ubiquinol oxidase from Escherichia coli resides in the
      bacterial cytoplasmic membrane and catalyzes the two-electron oxidation of
      ubiquinol-8 and four-electron reduction of O2 to water. The one-electron reduced
      semiquinone forms transiently during the reaction, and the enzyme has been
      demonstrated to stabilize the semiquinone. Two-dimensional electron spin echo
      envelope modulation has been applied to explore the exchangeable protons involved
      in hydrogen bonding to the semiquinone by substitution of 1H2O by 2H2O. Three
      exchangeable protons possessing different isotropic and anisotropic hyperfine
      couplings were identified. The strength of the hyperfine interaction with one
      proton suggests a significant covalent O-H binding of carbonyl oxygen O1 that is
      a characteristic of a neutral radical, an assignment that is also supported by
      the unusually large hyperfine coupling to the methyl protons. The second proton
      with a large anisotropic coupling also forms a strong hydrogen bond with a
      carbonyl oxygen. This second hydrogen bond, which has a significant out-of-plane
      character, is from an NH2 or NH nitrogen, probably from an arginine (Arg-71)
      known to be in the quinone binding site. Assignment of the third exchangeable
      proton with smaller anisotropic coupling is more ambiguous, but it is clearly not
      involved in a direct hydrogen bond with either of the carbonyl oxygens. The
      results support a model that the semiquinone is bound to the protein in a very
      asymmetric manner by two strong hydrogen bonds from Asp-75 and Arg-71 to the O1
      carbonyl, while the O4 carbonyl is not hydrogen-bonded to the protein.

PMID- 16624802
TI  - The importance of the strictly conserved, C-terminal glycine residue in
      phosphoenolpyruvate carboxylase for overall catalysis: mutagenesis and truncation
      of GLY-961 in the sorghum C4 leaf isoform.
AB  - Phosphoenolpyruvate carboxylase (PEPC) is a "multifaceted," allosteric enzyme
      involved in C4 acid metabolism in green plants/microalgae and prokaryotes. Before
      the elucidation of the three-dimensional structures of maize C4 leaf and
      Escherichia coli PEPC, our truncation analysis of the sorghum C4 homologue
      revealed important roles for the enzyme's C-terminal alpha-helix and its appended
      QNTG961 tetrapeptide in polypeptide stability and overall catalysis,
      respectively. Collectively, these functional and structural observations
      implicate the importance of the PEPC C-terminal tetrapeptide for both catalysis
      and negative allosteric regulation. We have now more finely dissected this
      element of PEPC structure-function by modification of the absolutely conserved C
      terminal glycine of the sorghum C4 isoform by site-specific mutagenesis
      (G961(A/V/D)) and truncation (DeltaC1/C4). Although the C4 polypeptide failed to
      accumulate in a PEPC- strain (XH11) of E. coli transformed with the Asp mutant,
      the other variants were produced at wild-type levels. Although neither of these
      four mutants displayed an apparent destabilization of the purified PEPC
      homotetramer, all were compromised catalytically in vivo and in vitro. Functional
      complementation of XH11 cells under selective growth conditions was restricted
      progressively by the Ala, DeltaC1 and Val, and DeltaC4 modifications. Likewise,
      steady-state kinetic analysis of the purified mutant enzymes revealed
      corresponding negative trends in kcat and kcat/K0.5 (phosphoenolpyruvate) but not
      in K0.5 or the Hill coefficient. Homology modeling of these sorghum C-terminal
      variants against the structure of the closely related maize C4 isoform predicted
      perturbations in active-site molecular cavities and/or ion-pairing with
      essential, invariant Arg-638. These collective observations reveal that even a
      modest, neutral alteration of the PEPC C-terminal hydrogen atom side chain is
      detrimental to enzyme function.

PMID- 16624803
TI  - Structure of RhlG, an essential beta-ketoacyl reductase in the rhamnolipid
      biosynthetic pathway of Pseudomonas aeruginosa.
AB  - Rhamnolipids are extracellular biosurfactants and virulence factors secreted by
      the opportunistic human pathogen Pseudomonas aeruginosa that are required for
      swarming motility. The rhlG gene is essential for rhamnolipid formation, and the
      RhlG enzyme is thought to divert fatty acid synthesis intermediates into the
      rhamnolipid biosynthetic pathway based on its similarity to FabG, the beta
      ketoacyl-acyl carrier protein (ACP) reductase of type II fatty acid synthesis.
      Crystallographic analysis reveals that the overall structures of the RhlG.NADP+
      and FabG.NADP+ complexes are indeed similar, but there are key differences
      related to function. RhlG does not undergo the conformational changes upon
      NADP(H) binding at the active site that in FabG are the structural basis of
      negative allostery. Also, the acyl chain-binding pocket of RhlG is narrow and
      rigid compared with the larger, flexible substrate-binding subdomain in FabG.
      Finally, RhlG lacks a positively charged/hydrophobic surface feature adjacent to
      the active site that is found on enzymes like FabG that recognize the ACP of
      fatty acid synthesis. RhlG catalyzed the NADPH-dependent reduction of beta
      ketodecanoyl-ACP to beta-d-hydroxydecanoyl-ACP. However, the enzyme was 2000-fold
      less active than FabG in carrying out the same reaction. These structural and
      biochemical studies establish RhlG as a NADPH-dependent beta-ketoacyl reductase
      of the SDR protein superfamily and further suggest that the ACP of fatty acid
      synthesis does not carry the substrates for RhlG.

PMID- 16624804
TI  - Crystal structure of the human FOXK1a-DNA complex and its implications on the
      diverse binding specificity of winged helix/forkhead proteins.
AB  - Interleukin enhancer binding factor (ILF) is a human transcription factor and a
      new member of the winged helix/forkhead family. ILF can bind to purine-rich
      regulatory motifs such as the human T-cell leukemia virus-long terminal region
      and the interleukin-2 promoter. Here we report the 2.4 A crystal structure of two
      DNA binding domains of ILF (FOXK1a) binding to a 16-bp DNA duplex containing a
      promoter sequence. Electrophoretic mobility shift assay studies demonstrate that
      two ILF-DNA binding domain molecules cooperatively bind to DNA. In addition to
      the recognition helix recognizing the core sequences through the major groove,
      the structure shows that wing 1 interacts with the minor groove of DNA, and the
      H2-H3 loop region makes ionic bonds to the phosphate group, which permits the
      recognition of DNA. The structure also reveals that the presence of the C
      terminal alpha-helix in place of a typical wing 2 in a member of this family
      alters the orientation of the C-terminal basic residues (RKRRPR) when binding to
      DNA outside the core sequence. These results provide a new insight into how the
      DNA binding specificities of winged helix/forkhead proteins may be regulated by
      their less conserved regions.

PMID- 16624805
TI  - ERK8 down-regulates transactivation of the glucocorticoid receptor through Hic-5.
AB  - Extracellular signal-regulated kinase 8 (ERK8) is the most recently identified
      member of the ERK subfamily of MAPKs. Although other members of the ERK subfamily
      are established regulators of signaling pathways involved in cell growth and/or
      differentiation, less is known about ERK8. To understand the cellular function of
      ERK8, a yeast two-hybrid screen of a human lung library was performed to identify
      binding partners. One binding partner identified was Hic-5 (also known as ARA55),
      a multiple LIM domain containing protein implicated in focal adhesion signaling
      and the regulation of specific nuclear receptors, including the androgen receptor
      and the glucocorticoid receptor (GR). Co-immunoprecipitation experiments in
      mammalian cells confirmed the interaction between Hic-5 and both ERK8 and its
      rodent ortholog ERK7. The C-terminal region of ERK8 was not required for the
      interaction. Although the LIM3 and LIM4 domains of Hic-5 were sufficient and
      required for this interaction, the specific zinc finger motifs in these domains
      were not. Transcriptional activation reporter assays revealed that ERK8 can
      negatively regulate transcriptional co-activation of androgen receptor and
      GRalpha by Hic-5 in a kinase-independent manner. Knockdown of endogenous ERK8 in
      human airway epithelial cells enhanced dexamethasone-stimulated transcriptional
      activity of endogenous GR. Transcriptional regulation of GRalpha and interaction
      with its ligand binding domain by ERK8 were dependent on the presence of Hic-5.
      These results provide the first physiological function for human ERK8 as a
      negative regulator of human GRalpha, acting through Hic-5, and suggest a broader
      role for ERK8 in the regulation of nuclear receptors beyond estrogen receptor
      alpha.

PMID- 16624806
TI  - First AID (activation-induced cytidine deaminase) is needed to produce high
      affinity isotype-switched antibodies.

PMID- 16624807
TI  - Biogenesis of functional antigenic peptide transporter TAP requires assembly of
      pre-existing TAP1 with newly synthesized TAP2.
AB  - The transporter associated with antigen processing (TAP) is essential for the
      delivery of antigenic peptides from the cytosol into the endoplasmic reticulum
      (ER), where they are loaded onto major histocompatibility complex class I
      molecules. TAP is a heterodimeric transmembrane protein that comprises the
      homologous subunits TAP1 and TAP2. As for many other oligomeric protein
      complexes, which are synthesized in the ER, the process of subunit assembly is
      essential for TAP to attain a native functional state. Here, we have analyzed the
      individual requirements of TAP1 and TAP2 for the formation of a functional TAP
      complex. Unlike TAP1, TAP2 is very unstable when expressed in isolation. We show
      that heterodimerization of TAP subunits is required for maintaining a stable
      level of TAP2. By using an in vitro expression system we demonstrate that the
      biogenesis of functional TAP depends on the assembly of preexisting TAP1 with
      newly synthesized TAP2, but not vice versa. The pore forming core transmembrane
      domain (core TMD) of in vitro expressed TAP2 is necessary and sufficient to allow
      functional complex formation with pre-existing TAP1. We propose that the observed
      assembly mechanism of TAP protects newly synthesized TAP2 from rapid degradation
      and controls the number of transport active transporter molecules. Our findings
      open up new possibilities to investigate functional and structural properties of
      TAP and provide a powerful model system to address the biosynthetic assembly of
      oligomeric transmembrane proteins in the ER.

PMID- 16624808
TI  - Domain interactions within Fzo1 oligomers are essential for mitochondrial fusion.
AB  - Mitofusins are conserved GTPases essential for the fusion of mitochondria. These
      mitochondrial outer membrane proteins contain a GTPase domain and two or three
      regions with hydrophobic heptad repeats, but little is known about how these
      domains interact to mediate mitochondrial fusion. To address this issue, we have
      analyzed the yeast mitofusin Fzo1p and find that mutation of any of the three
      heptad repeat regions (HRN, HR1, and HR2) leads to a null allele. Specific pairs
      of null alleles show robust complementation, indicating that functional domains
      need not exist on the same molecule. Biochemical analysis indicates that this
      complementation is due to Fzo1p oligomerization mediated by multiple domain
      interactions. Moreover, we find that two non-overlapping protein fragments, one
      consisting of HRN/GTPase and the other consisting of HR1/HR2, can form a complex
      that reconstitutes Fzo1p fusion activity. Each of the null alleles disrupts the
      interaction of these two fragments, suggesting that we have identified a key
      interaction involving the GTPase domain and heptad repeats essential for fusion.

PMID- 16624809
TI  - Two-photon imaging of glutathione levels in intact brain indicates enhanced redox
      buffering in developing neurons and cells at the cerebrospinal fluid and blood
      brain interface.
AB  - Glutathione is the major cellular thiol present in mammalian cells and is
      critical for maintenance of redox homeostasis. However, current assay systems for
      glutathione lack application to intact animal tissues. To map the levels of
      glutathione in intact brain with cellular resolution (acute tissue slices and
      live animals), we have used two-photon imaging of monochlorobimane fluorescence,
      a selective enzyme-mediated marker for reduced glutathione. Previously, in vitro
      experiments using purified components and cultured glial cells attributed
      cellular monochlorobimane fluorescence to a glutathione S-transferase-dependent
      reaction with GSH. Our results indicate that cells at the cerebrospinal fluid or
      blood-brain interface, such as lateral ventricle ependymal cells (2.73 +/- 0.56
      mm; glutathione), meningeal cells (1.45 +/- 0.09 mm), and astroglia (0.91 +/-
      0.08 mm), contain high levels of glutathione. In comparison, layer II cortical
      neurons contained 20% (0.21 +/- 0.02 mm) the glutathione content of nearby
      astrocytes. Neuronal glutathione labeling increased 250% by the addition of the
      cell-permeable glutathione precursor N-acetylcysteine indicating that the
      monochlorobimane level or glutathione S-transferase activity within neurons was
      not limiting. Regional mapping showed that glutathione was highest in cells
      lining the lateral ventricles, specifically ependymal cells and the
      subventricular zone, suggesting a possible function for glutathione in oxidant
      homeostasis of developing neuronal progenitors. Consistently, developing neurons
      in the subgranular zone of dentate gyrus contained 3-fold more glutathione than
      older neurons found in the neighboring granular layer. In conclusion, mapping of
      glutathione levels in intact brain demonstrates a unique role for enhanced redox
      potential in developing neurons and cells at the cerebrospinal fluid and blood
      brain interface.

PMID- 16624810
TI  - The two-stage pathway of ataxin-3 fibrillogenesis involves a polyglutamine
      independent step.
AB  - The aggregation of ataxin-3 is associated with spinocerebellar ataxia type 3,
      which is characterized by the formation of intraneuronal aggregates. However, the
      mechanism of aggregation is currently not well understood. Ataxin-3 consists of a
      folded Josephin domain followed by two ubiquitin-interacting motifs and a C
      terminal polyglutamine tract, which in the non-pathological form is less than 45
      residues in length. We demonstrate that ataxin-3 with 64 glutamines (at(Q64))
      undergoes a two-stage aggregation. The first stage involves formation of SDS
      soluble aggregates, and the second stage results in formation of SDS-insoluble
      aggregates via the poly(Q) region. Both these first and second stage aggregates
      display typical amyloid-like characteristics. Under the same conditions at(Q15)
      and at(QHQ) undergo a single step aggregation event resulting in SDS-soluble
      aggregates, which does not involve the polyglutamine tract. These aggregates do
      not convert to the SDS-insoluble form. These observations demonstrate that ataxin
      3 has an inherent capacity to aggregate through its non-polyglutamine domains.
      However, the presence of a pathological length polyglutamine tract introduces an
      additional step resulting in formation of a highly stable amyloid-like aggregate.

PMID- 16624811
TI  - Lys-D48 is required for charge stabilization, rapid flavin reduction, and
      internal electron transfer in the catalytic cycle of dihydroorotate dehydrogenase
      B of Lactococcus lactis.
AB  - Dihydroorotate dehydrogenase B (DHODB) catalyzes the oxidation of dihydroorotate
      (DHO) to orotate and is found in the pyrimidine biosynthetic pathway. The
      Lactococcus lactis enzyme is a dimer of heterodimers containing FMN, FAD, and a
      2Fe-2S center. Lys-D48 is found in the catalytic subunit and its side-chain
      adopts different positions, influenced by ligand binding. Based on crystal
      structures of DHODB in the presence and absence of orotate, we hypothesized that
      Lys-D48 has a role in facilitating electron transfer in DHODB, specifically in
      stabilizing negative charge in the reduced FMN isoalloxazine ring. We show that
      mutagenesis of Lys-D48 to an alanine, arginine, glutamine, or glutamate residue
      (mutants K38A, K48R, K48Q, and K48E) impairs catalytic turnover substantially
      (approximately 50-500-fold reduction in turnover number). Stopped-flow studies
      demonstrate that loss of catalytic activity is attributed to poor rates of FMN
      reduction by substrate. Mutation also impairs electron transfer from the 2Fe-2S
      center to FMN. Addition of methylamine leads to partial rescue of flavin
      reduction activity. Nicotinamide coenzyme oxidation and reduction at the distal
      FAD site is unaffected by the mutations. Formation of the spin-interacting state
      between the FMN semiquinone-reduced 2Fe-2S centers observed in wild-type enzyme
      is retained in the mutant proteins, consistent with there being little
      perturbation of the superexchange paths that contribute to the efficiency of
      electron transfer between these cofactors. Our data suggest a key charge
      stabilizing role for Lys-D48 during reduction of FMN by dihydroorotate, or by
      electron transfer from the 2Fe-2S center, and establish a common mechanism of FMN
      reduction in the single FMN-containing A-type and the complex multicenter B-type
      DHOD enzymes.

PMID- 16624812
TI  - Excess HDM2 impacts cell cycle and apoptosis and has a selective effect on p53
      dependent transcription.
AB  - Mutational inactivation of p53 is only one of the ways that tumors lose p53
      function. An alternate route is through overexpression of HDM2, the negative
      regulator of p53. To further understand how excess HDM2 regulates p53-mediated
      functions, we generated H1299 cell clones that constitutively express both
      ectopic HDM2 and tetracycline-regulated inducible p53. We found that over a range
      of p53 concentrations constitutively expressed HDM2 did not affect the levels of
      p53 protein. Nevertheless, cells with excess HDM2 displayed numerous changes in
      their response to p53. After DNA damage, such cells had both increased p53
      mediated G2 arrest and reduced cell death. They also showed selective impairment
      of p53 target gene induction in that some p53 targets were unaffected whereas
      others were markedly less well induced in the presence of extra HDM2 protein. We
      also found that excess HDM2 was correlated with reduced p53 acetylation but did
      not affect p53 association with target promoters in vivo. Indeed, there was no
      significant difference in the amount of HDM2 associated with p53 at target
      promoters that differed in their expression depending on the presence of extra
      HDM2. Thus, HDM2 can selectively down-regulate the transcription function of p53
      without either degrading p53 or affecting the interaction of p53 with target
      promoters.

PMID- 16624813
TI  - The structural integrity of anion binding exosite I of thrombin is required and
      sufficient for timely cleavage and activation of factor V and factor VIII.
AB  - Alpha-thrombin has two separate electropositive binding exosites (anion binding
      exosite I, ABE-I and anion binding exosite II, ABE-II) that are involved in
      substrate tethering necessary for efficient catalysis. Alpha-thrombin catalyzes
      the activation of factor V and factor VIII following discrete proteolytic
      cleavages. Requirement for both anion binding exosites of the enzyme has been
      suggested for the activation of both procofactors by alpha-thrombin. We have used
      plasma-derived alpha-thrombin, beta-thrombin (a thrombin molecule that has only
      ABE-II available), and a recombinant prothrombin molecule rMZ-II
      (R155A/R284A/R271A) that can only be cleaved at Arg(320) (resulting in an
      enzymatically active molecule that has only ABE-I exposed, rMZ-IIa) to ascertain
      the role of each exosite for procofactor activation. We have also employed a
      synthetic sulfated pentapeptide (DY(SO(3)(-))DY(SO(3)(-))Q, designated D5Q1,2) as
      an exosite-directed inhibitor of thrombin. The clotting time obtained with beta
      thrombin was increased by approximately 8-fold, whereas rMZ-IIa was 4-fold less
      efficient in promoting clotting than alpha-thrombin under similar experimental
      conditions. Alpha-thrombin readily activated factor V following cleavages at
      Arg(709), Arg(1018), and Arg(1545) and factor VIII following proteolysis at
      Arg(372), Arg(740), and Arg(1689). Cleavage of both procofactors by alpha
      thrombin was significantly inhibited by D5Q1,2. In contrast, beta-thrombin was
      unable to cleave factor V at Arg(1545) and factor VIII at both Arg(372) and
      Arg(1689). The former is required for light chain formation and expression of
      optimum factor Va cofactor activity, whereas the latter two cleavages are a
      prerequisite for expression of factor VIIIa cofactor activity. Beta-thrombin was
      found to cleave factor V at Arg(709) and factor VIII at Arg(740), albeit less
      efficiently than alpha-thrombin. The sulfated pentapeptide inhibited moderately
      both cleavages by beta-thrombin. Under similar experimental conditions, membrane
      bound rMZ-IIa cleaved and activated both procofactor molecules. Activation of the
      two procofactors by membrane-bound rMZ-IIa was severely impaired by D5Q1,2.
      Overall the data demonstrate that ABE-I alone of alpha-thrombin can account for
      the interaction of both procofactors with alpha-thrombin resulting in their
      timely and efficient activation. Because formation of meizothrombin precedes that
      of alpha-thrombin, our findings also imply that meizothrombin may be the
      physiological activator of both procofactors in vivo in the presence of a
      procoagulant membrane surface during the early stages of coagulation.

PMID- 16624814
TI  - ADAM10 activation is required for green tea (-)-epigallocatechin-3-gallate
      induced alpha-secretase cleavage of amyloid precursor protein.
AB  - Recently, we have shown that green tea polyphenol (-)-epigallocatechin-3-gallate
      (EGCG) exerts a beneficial role on reducing brain Abeta levels, resulting in
      mitigation of cerebral amyloidosis in a mouse model of Alzheimer disease. EGCG
      seems to accomplish this by modulating amyloid precursor protein (APP)
      processing, resulting in enhanced cleavage of the alpha-COOH-terminal fragment
      (alpha-CTF) of APP and corresponding elevation of the NH(2)-terminal APP product,
      soluble APP-alpha (sAPP-alpha). These beneficial effects were associated with
      increased alpha-secretase cleavage activity, but no significant alteration in
      beta-or gamma-secretase activities. To gain insight into the molecular mechanism
      whereby EGCG modulates APP processing, we evaluated the involvement of three
      candidate alpha-secretase enzymes, a-disintegrin and metalloprotease (ADAM) 9,
      10, or 17, in EGCG-induced non-amyloidogenic APP metabolism. Results show that
      EGCG treatment of N2a cells stably transfected with "Swedish" mutant human APP
      (SweAPP N2a cells) leads to markedly elevated active ( approximately 60 kDa
      mature form) ADAM10 protein. Elevation of active ADAM10 correlates with increased
      alpha-CTF cleavage, and elevated sAPP-alpha. To specifically test the
      contribution of ADAM10 to non-amyloidogenic APP metabolism, small interfering RNA
      knockdown of ADAM9, -10, or -17 mRNA was employed. Results show that ADAM10 (but
      not ADAM9 or -17) is critical for EGCG-mediated alpha-secretase cleavage
      activity. In summary, ADAM10 activation is necessary for EGCG promotion of non
      amyloidogenic (alpha-secretase cleavage) APP processing. Thus, ADAM10 represents
      an important pharmacotherapeutic target for the treatment of cerebral amyloidosis
      in Alzheimer disease.

PMID- 16624815
TI  - Vascular endothelial growth factor-D activates VEGFR-3 expressed in osteoblasts
      inducing their differentiation.
AB  - Vascular endothelial growth factor (VEGF)-D is a member of the VEGF family of
      angiogenic growth factors that recognizes and activates the vascular endothelial
      growth factor receptor (VEGFR)-2 and VEGFR-3 on blood and/or lymphatic vessels.
      We show that in the long bones of newborn mice, VEGF-D and VEGFR-3 are expressed
      in the osteoblasts of the growing plate. The treatment of primary human
      osteoblasts with recombinant VEGF-D induces the expression of osteocalcin and the
      formation of mineralized nodules in a dose-dependent manner. A monoclonal
      neutralizing antibody, anti-VEGF-D, or silencing of VEGFR-3 by lentiviral
      mediated expression of VEGFR-3 small hairpin RNA affects VEGF-D-dependent
      osteocalcin expression and nodule formation. Moreover, in primary human
      osteoblasts, VEGF-D expression is under the control of VEGF, and inhibition of
      VEGF-D/VEGFR-3 signaling, by monoclonal antibodies or VEGFR-3 silencing, affects
      VEGF-dependent osteoblast differentiation. These experiments establish that VEGF
      D/VEGFR-3 signaling plays a critical role in osteoblast maturation and suggest
      that VEGF-D is a downstream effector of VEGF in osteogenesis.

PMID- 16624816
TI  - Heat shock protein 25 or inducible heat shock protein 70 activates heat shock
      factor 1: dephosphorylation on serine 307 through inhibition of ERK1/2
      phosphorylation.
AB  - The expression of heat shock proteins (HSPs) is known to be increased via
      activation of heat shock factor 1 (HSF1), and excess expression of HSPs exerts
      feedback inhibition of HSF1. However, the molecular mechanism to modulate such
      relationships between HSPs and HSF1 is not clear. In the present study, we show
      that stable transfection of either Hsp25 or inducible Hsp70 (Hsp70i) increased
      expression of endogenous HSPs such as HSP25 and HSP70i through HSF1 activation.
      However, these phenomena were abolished when the dominant negative Hsf1 mutant
      was transfected to HSP25 or HSP70i overexpressed cells. Moreover, the increased
      HSF1 activity by either HSP25 or HSP70i was found to result from
      dephosphorylation of HSF1 on serine 307 that increased the stability of HSF1.
      Either HSP25 or HSP70i inhibited ERK1/2 phosphorylation because of increased MKP1
      phosphorylation by direct interaction of these HSPs with MKP1. Treatment of HOS
      and NCI-H358 cells, which showed high expressions of endogenous HSF1, with small
      interfering RNA (siRNA) of either HSP27 (siHSP27)or HSP70i (siHSP70i) inhibited
      both HSP27 and HSP70i proteins; this was because of increased ERK1/2
      phosphorylation and serine phosphorylation of HSF1. The results, therefore,
      suggested that when the HSF1 protein level was high in cancer cells, excess
      expression of HSP27 or HSP70i strongly facilitates the expression of HSP proteins
      through HSF1 activation, resulting in severe radio- or chemoresistance.

PMID- 16624817
TI  - Neuroprotection of Tat-GluR6-9c against neuronal death induced by kainate in rat
      hippocampus via nuclear and non-nuclear pathways.
AB  - Previous studies have suggested that glutamate receptor 6 (GluR6) subunit- and
      JNK-deficient mice can resist kainate-induced epileptic seizure and neuronal
      toxicity (Yang, D. D., Kuan, C.-Y., Whitmarsh, A. J., Rinocn, M., Zheng, T. S.,
      Davis, R. J., Rakic, P., and Flavell, R. A. (1997) Nature 389, 865-870; Mulle,
      C., Seiler, A., Perez-Otano, I., Dickinson-Anson, H., Castillo, P. E., Bureau,
      I., Maron, C., Gage, F. H., Mann, J. R., Bettler, B., and Heinemmann, S. F.
      (1998) Nature 392, 601-605). In this study, we show that kainate can enhance the
      assembly of the GluR6-PSD95-MLK3 module and facilitate the phosphorylation of JNK
      in rat hippocampal CA1 and CA3/dentate gyrus (DG) subfields. More important, a
      peptide containing the Tat protein transduction sequence (Tat-GluR6-9c) perturbed
      the assembly of the GluR6-PSD95-MLK3 signaling module and suppressed the
      activation of MLK3, MKK7, and JNK. As a result, the inhibition of JNK activation
      by Tat-GluR6-9c diminished the phosphorylation of the transcription factor c-Jun
      and down-regulated Fas ligand expression in hippocampal CA1 and CA3/DG regions.
      The inhibition of JNK activation by Tat-Glur6-9c attenuated Bax translocation,
      the release of cytochrome c, and the activation of caspase-3 in CA1 and CA3/DG
      subfields. Furthermore, kainate-induced neuronal loss in hippocampal CA1 and CA3
      subregions was prevented by intracerebroventricular injection of Tat-Glur6 - 9c.
      Taken together, our findings strongly suggest that the GluR6-PSD95-MLK3 signaling
      module mediates activation of the nuclear and non-nuclear pathways of JNK, which
      is involved in brain injury induced by kainate. Tat-GluR6-9c, the peptide we
      constructed, gives new insight into seizure therapy.

PMID- 16624818
TI  - Complementation of Saccharomyces cerevisiae coq7 mutants by mitochondrial
      targeting of the Escherichia coli UbiF polypeptide: two functions of yeast Coq7
      polypeptide in coenzyme Q biosynthesis.
AB  - Coenzyme Q (ubiquinone or Q) functions in the respiratory electron transport
      chain and serves as a lipophilic antioxidant. In the budding yeast Saccharomyces
      cerevisiae, Q biosynthesis requires nine Coq proteins (Coq1-Coq9). Previous work
      suggests both an enzymatic activity and a structural role for the yeast Coq7
      protein. To define the functional roles of yeast Coq7p we test whether
      Escherichia coli ubiF can functionally substitute for yeast COQ7. The ubiF gene
      encodes a flavin-dependent monooxygenase that shares no homology to the Coq7
      protein and is required for the final monooxygenase step of Q biosynthesis in E.
      coli. The ubiF gene expressed at low copy restores growth of a coq7 point mutant
      (E194K) on medium containing a non-fermentable carbon source, but fails to rescue
      a coq7 null mutant. However, expression of ubiF from a multicopy vector restores
      growth and Q synthesis for both mutants, although with a higher efficiency in the
      point mutant. We attribute the more efficient rescue of the coq7 point mutant to
      higher steady state levels of the Coq3, Coq4, and Coq6 proteins and to the
      presence of demethoxyubiquinone, the substrate of UbiF. Coq7p co-migrates with
      the Coq3 and Coq4 polypeptides as a high molecular mass complex. Here we show
      that addition of Q to the growth media also stabilizes the Coq3 and Coq4
      polypeptides in the coq7 null mutant. The data suggest that Coq7p, and the lipid
      quinones (demethoxyubiquinone and Q) function to stabilize other Coq
      polypeptides.

PMID- 16624819
TI  - Chondroitin sulfate intake inhibits the IgE-mediated allergic response by down
      regulating Th2 responses in mice.
AB  - Chondroitin sulfate (CS) was administered orally to BALB/c mice immunized
      intraperitoneally with ovalbumin (OVA) and/or dinitrophenylated OVA. The titers
      of antigen-specific IgE and IgG1 in mouse sera were determined. The antigen
      specific IgE production by mice fed ad libitum with CS was significantly
      inhibited. We also examined the effect of feeding CS on immediate-type
      hypersensitivity. One hour after antigen stimulation, the ears of mice fed with
      CS swelled less than those of the control mice. Furthermore, the rise in serum
      histamine in the mice fed with CS under active systemic anaphylaxis was
      significantly lower than that in the controls. We next examined the pattern of
      cytokine production by splenocytes from mice followed by re-stimulation with OVA
      in vitro. The splenocytes from the mice fed with CS produced less interleukin
      (IL)-5, IL-10, and IL-13 than those from the control group. In contrast, the
      production of interferon-gamma and IL-2 by the splenocytes of mice fed with CS
      was not significantly different from those in the control mice. In addition, the
      production of transforming growth factor-beta from the splenocytes of mice fed
      with CS was significantly higher than that of the control mice. Furthermore, we
      showed that the percentages of CD4(+) cells, CD8(+) cells, and CD4(+)CD25(+)
      cells in the splenocytes of mice fed with CS are significantly higher than those
      of the control. These findings suggest that oral intake of CS inhibits the
      specific IgE production and antigen-induced anaphylactic response by up
      regulating regulatory T-cell differentiation, followed by down-regulating the Th2
      response.

PMID- 16624820
TI  - Affinity-defining domains in the Na-Cl cotransporter: a different location for Cl
      and thiazide binding.
AB  - The thiazide-sensitive Na+-Cl- cotransporter (NCC) is the major pathway for salt
      reabsorption in the distal convoluted tubule, serves as a receptor for thiazide
      type diuretics, and is involved in inherited diseases associated with abnormal
      blood pressure. Little is known regarding the structure-function relationship in
      this cotransporter. Previous studies from our group reveal that mammalian NCC
      exhibits higher affinity for ions and thiazides than teleost NCC and suggest a
      role for glycosylation upon thiazide affinity. Here we have constructed a series
      of chimeric and mutant cDNAs between rat and flounder NCC to define the role of
      glycosylation status, the amino-terminal domain, the carboxyl-terminal domain,
      the extracellular glycosylated loop, and the transmembrane segments upon affinity
      for Na+, Cl-, and metolazone. Xenopus laevis oocytes were used as the
      heterologous expression system. We observed that elimination of glycosylation
      sites in flounder NCC did not affect the affinity of the cotransporter for
      metolazone. Also, swapping the amino-terminal domain, the carboxyl-terminal
      domain, the glycosylation sites, or the entire extracellular glycosylation loop
      between rat and flounder NCC had no effect upon ions or metolazone affinity. In
      contrast, interchanging transmembrane regions between rat and flounder NCC
      revealed that affinity-modifying residues for chloride are located within the
      transmembrane 1-7 region and for thiazides are located within the transmembrane 8
      12 region, whereas both segments seem to be implicated in defining sodium
      affinity. These observations strongly suggest that binding sites for chloride and
      thiazide in NCC are different.

PMID- 16624821
TI  - Evidence against functionally significant aquaporin expression in mitochondria.
AB  - Recent reports suggest the expression of aquaporin (AQP)-type water channels in
      mitochondria from liver (AQP8) (Calamita, G., Ferri, D., Gena, P., Liquori, G.
      E., Cavalier, A., Thomas, D., and Svelto, M. (2005) J. Biol. Chem. 280, 17149
      17153) and brain (AQP9) (Amiry-Moghaddam, M., Lindland, H., Zelenin, S., Roberg,
      B. A., Gundersen, B. B., Petersen, P., Rinvik, E., Torgner, I. A., and Ottersen,
      O. P. (2005) FASEB J. 19, 1459-1467), where they were speculated to be involved
      in metabolism, apoptosis, and Parkinson disease. Here, we systematically examined
      the functional consequence of AQP expression in mitochondria by measurement of
      water and glycerol permeabilities in mitochondrial membrane preparations from rat
      brain, liver, and kidney and from wild-type versus knock-out mice deficient in
      AQPs -1, -4, or -8. Osmotic water permeability, measured by stopped-flow light
      scattering, was similar in all mitochondrial preparations, with a permeability
      coefficient P(f) approximately 0.009 cm/s. Glycerol permeability was also similar
      ( approximately 5 x 10(-6) cm/s) in the various preparations. HgCl(2) slowed
      osmotic equilibration comparably in mitochondria from wild-type and AQP-deficient
      mice, although the slowing was explained by altered mitochondrial size rather
      than reduced P(f). Immunoblot analysis of mouse liver mitochondria failed to
      detect AQP8 expression, with liver homogenates from wild-type/AQP8 null mice as
      positive/negative controls. Our results provide evidence against functionally
      significant AQP expression in mitochondria, which is consistent with the high
      mitochondrial surface-to-volume ratio producing millisecond osmotic
      equilibration, even when intrinsic membrane water permeability is not high.

PMID- 16624822
TI  - Jab1 induces the cytoplasmic localization and degradation of p53 in coordination
      with Hdm2.
AB  - The biological mechanisms for maintaining the basal level of p53 in normal cells
      require nuclear exclusion and cytoplasmic degradation. Here, we showed that Jab1
      facilitates p53 nuclear exclusion and its subsequent degradation in coordination
      with Hdm2. p53 was excluded from the nucleus in the presence of Jab1; this
      exclusion was prevented by leptomycin B treatment. Nuclear export of p53 was
      accompanied by a decrease in the levels of p53, as well as of its target
      proteins, which include p21 and Bax. Domain analyses of Jab1 showed that the N
      terminal domain, 1-110, was capable of inducing cytoplasmic translocation of p53.
      Furthermore, 110-191 was required to facilitate the degradation of p53. Neither
      of these mutants incorporated into the CSN complex, indicating that Jab1 could
      affect the levels of p53 independent of intact CSN complex. Conversely, Jab1 was
      incapable of translocating and degrading two p53 mutants, W23S and 6KR, neither
      of which could be modified by Hdm2. Moreover, Jab1 did not affect the cellular
      localization or protein levels of p53 in p53 and Hdm2 double-null mouse embryo
      fibroblasts. We further observed that the ablation of endogenous Jab1 by small
      interfering RNA prevented Hdm2-mediated p53 nuclear exclusion. Under stressed
      conditions, which could sequester Hdm2 in its inactive state, Jab1 did not affect
      p53. Our studies implicate that Jab1 is required to remove post-translationally
      modified p53 and provide a novel target for p53-related cancer therapies.

PMID- 16624823
TI  - Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappaB activation
      and NF-kappaB-regulated gene products through modulation of p65 and IkappaBalpha
      kinase activation, leading to potentiation of apoptosis induced by cytokine and
      chemotherapeutic agents.
AB  - Plumbagin, derived from the medicinal plant Plumbago zeylanica, modulates
      cellular proliferation, carcinogenesis, and radioresistance, all known to be
      regulated by the activation of the transcription factor NF-kappaB, suggesting
      plumbagin might affect the NF-kappaB activation pathway. We found that plumbagin
      inhibited NF-kappaB activation induced by TNF, and other carcinogens and
      inflammatory stimuli (e.g. phorbol 12-myristate 13-acetate, H2O2, cigarette smoke
      condensate, interleukin-1beta, lipopolysaccharide, and okadaic acid). Plumbagin
      also suppressed the constitutive NF-kappaB activation in certain tumor cells. The
      suppression of NF-kappaB activation correlated with sequential inhibition of the
      tumor necrosis factor (TNF)-induced activation of IkappaBalpha kinase,
      IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65
      nuclear translocation, and the NF-kappaB-dependent reporter gene expression
      activated by TNF, TNFR1, TRAF2, NIK, IKK-beta, and the p65 subunit of NF-kappaB.
      Plumbagin also suppressed the direct binding of nuclear p65 and recombinant p65
      to the DNA, and this binding was reversed by dithiothreitol both in vitro and in
      vivo. However, plumbagin did not inhibit p65 binding to DNA when cells were
      transfected with the p65 plasmid containing cysteine 38 mutated to serine.
      Plumbagin down-regulated the expression of NF-kappaB-regulated anti-apoptotic
      (IAP1, IAP2, Bcl-2, Bcl-xL, cFLIP, Bfl-1/A1, and survivin), proliferative (cyclin
      D1 and COX-2), and angiogenic (matrix metalloproteinase-9 and vascular
      endothelial growth factor) gene products. This led to potentiation of apoptosis
      induced by TNF and paclitaxel and inhibited cell invasion. Overall, our results
      indicate that plumbagin is a potent inhibitor of the NF-kappaB activation pathway
      that leads to suppression of NF-kappaB-regulated gene products. This may explain
      its cell growth modulatory, anticarcinogenic, and radiosensitizing effects
      previously described.

PMID- 16624824
TI  - OEP37 is a new member of the chloroplast outer membrane ion channels.
AB  - The chloroplast outer envelope protein OEP37 is a member of the growing beta
      barrel protein family of the outer chloroplast membrane. The reconstituted
      recombinant protein OEP37 from pea forms a rectifying high conductance channel
      with a main conductance (lambda) of Lambda= 500 picosiemens (symmetrical 250 mm
      KCl). The OEP37 channel is cation-selective (P(K+)/P(K-) = 14:1) with a voltage
      dependent open probability maximal at V(mem) = 0 mV. The channel pore reveals an
      hourglass-shaped form with different diameters for the vestibule and restriction
      zone. The diameters of the vestibule at the high conductance side were estimated
      by d = 3.0 nm and the restriction zone by d = 1.5 nm. The OEP37 channel displayed
      a nanomolar affinity for the precursor of the chloroplast inner membrane protein
      Tic32, which is imported into the chloroplast through a yet unknown pathway. Pre
      proteins imported through the usual Toc pathway and synthetic control peptides,
      however, did not show a comparable block of the OEP37 channel. In addition to the
      electrophysiological characterization, we studied the gene expression of OEP37 in
      the model plant Arabidopsis thaliana. Here, transcripts of AtOEP37 are
      ubiquitously expressed throughout plant development and accumulate in early
      germinating seedlings as well as in late embryogenesis. The plastid intrinsic
      protein could be detected in isolated chloroplasts of cotyledons and rosette
      leaves. However, the knock-out mutant oep37-1 shows that the proper function of
      this single copy gene is not essential for development of the mature plant.
      Moreover, import of Tic32 into chloroplasts of oep37-1 was not impaired when
      compared with wild type. Thus, OEP37 may constitute a novel peptide-sensitive ion
      channel in the outer envelope of plastids with function during embryogenesis and
      germination.

PMID- 16624825
TI  - Catch bond-mediated adhesion without a shear threshold: trimannose versus
      monomannose interactions with the FimH adhesin of Escherichia coli.
AB  - The FimH protein is the adhesive subunit of Escherichia coli type 1 fimbriae. It
      mediates shear-dependent bacterial binding to monomannose (1M)-coated surfaces
      manifested by the existence of a shear threshold for binding, below which
      bacteria do not adhere. The 1M-specific shear-dependent binding of FimH is
      consistent with so-called catch bond interactions, whose lifetime is increased by
      tensile force. We show here that the oligosaccharide-specific interaction of FimH
      with another of its ligands, trimannose (3M), lacks a shear threshold for
      binding, since the number of bacteria binding under static conditions is higher
      than under any flow. However, similar to 1M, the binding strength of surface
      interacting bacteria is enhanced by shear. Bacteria transition from rolling into
      firm stationary surface adhesion as the shear increases. The shear-enhanced
      bacterial binding on 3M is mediated by catch bond properties of the 1M-binding
      subsite within the extended oligosaccharide-binding pocket of FimH, since
      structural mutations in the putative force-responsive region and in the binding
      site affect 1M- and 3M-specific binding in an identical manner. A shear-dependent
      conversion of the adhesion mode is also exhibited by P-fimbriated E. coli
      adhering to digalactose surfaces.

PMID- 16624827
TI  - Inhibition of proliferation and induction of apoptosis in human breast cancer
      cells by lauryl gallate.
AB  - Lauryl gallate is an antioxidant food additive showing low toxicity to normal
      cells. Here, its antiproliferative effect has been studied on three human breast
      cancer cell lines: estrogen-dependent, wild-type p53, MCF7; estrogen-independent,
      non-functional p53, MDA-MB-231 and MCF7 ADR, which overexpresses P-glycoprotein
      (P-gp) and displays a multidrug-resistant phenotype. Lauryl gallate inhibited
      proliferation and induced cell cycle alterations in all three cell lines without
      altering P-gp functionality in the drug-resistant cells. A stable arrest in G(1)
      phase was observed in MCF7, while a slow-down of cell cycle progression was
      induced in the other two cell lines. Lauryl gallate increased p53 expression only
      in MCF7, and upregulated p21(Cip1) and reduced cyclin D1 levels in all three cell
      lines. The induction of apoptosis, demonstrated by annexin V-FITC labeling, PARP
      cleavage and mitochondrial membrane depolarization and morphological alterations,
      were clearly detected in MCF7 ADR and MDA-MB-231 and to a minor extent in MCF7.
      Overexpression of Bcl-2 in MCF7 ADR cells demonstrated its protective role
      against morphological alterations and apoptosis. Lauryl gallate induction of
      p21(Cip1) and apoptosis observed in all three cell lines was regulated by Erk1/2
      activation. These findings suggest a potential use of lauryl gallate against
      tumors harboring p53 mutations and drug-resistant phenotypes.

PMID- 16624826
TI  - The timing of endocytosis after activation of a G-protein-coupled receptor in a
      sensory neuron.
AB  - Endocytosis is a fundamental cellular event in membrane retrieval after
      exocytosis and in the regulation of receptor-mediated signal transduction. In
      contrast to the well-studied depolarization-induced membrane recycling, little is
      known about the kinetics of ligand-induced endocytosis of G-protein-coupled
      receptors in neurons. Here we investigated the kinetics of ligand-receptor
      binding-induced endocytosis in rat sensory neurons using a membrane capacitance
      assay. The time constant of ADP-induced endocytosis of P2Y-receptors was
      determined as 1.7 s. The ADP-induced endocytosis was blocked by antagonists
      against P2Y, phosphorylation, and clathrin. However, block of dynamin was without
      effect. The ADP-induced endocytosis was confirmed independently by a single
      vesicle image technique using a styryl FM2-10. Finally, the receptors were
      internalized in response to ADP, as determined by GFP-labeled P2Y. We conclude
      that ligand-receptor binding leads to rapid endocytosis in the cytoplasm of rat
      dorsal root ganglion neurons.

PMID- 16624828
TI  - 1alpha, 25-dihydroxyvitamin D3 suppresses interleukin-8-mediated prostate cancer
      cell angiogenesis.
AB  - Angiogenesis is an essential step in initial tumor development and metastasis.
      Consequently, compounds that inhibit angiogenesis would be useful in treating
      cancer. A variety of antitumor effects mediated by 1alpha, 25-dihydroxyvitamin D3
      (1,25-VD) have been reported, one of which is anti-angiogenesis; however,
      detailed mechanisms remain unclear. We have demonstrated that 1,25-VD inhibits
      prostate cancer (PCa) cell-induced human umbilical vein endothelial cell
      migration and tube formation, two critical steps involved in the angiogenesis. An
      angiogenesis factor, interleukin-8 (IL-8), secreted from PCa cell was suppressed
      by 1,25-VD at both mRNA and protein levels. Mechanistic dissection found that
      1,25-VD inhibits NF-kappaB signal, one of the most important IL-8 upstream
      regulators. The 1,25-VD-mediated NF-kappaB signal reduction was shown to result
      from the blocking of nuclear translocation of p65, a subunit of the NF-kappaB
      complex, and was followed by attenuation of the NF-kappaB complex binding to DNA.
      The role of IL-8 in PCa progression was further examined by PCa tissue microarray
      analyses. We found that IL-8 expression was elevated during PCa progression,
      which suggests that IL-8 may play a role in tumor progression mediated through
      its stimulation on angiogenesis. These findings indicate that 1,25-VD could
      prevent PCa progression by interrupting IL-8 signaling, which is required in
      tumor angiogenesis, and thus applying vitamin D in PCa treatment may be
      beneficial for controlling disease progression.

PMID- 16624829
TI  - Effects of glutathione S-transferase A1 (GSTA1) genotype and potential modifiers
      on breast cancer risk.
AB  - Glutathione S-transferases (GSTs) are phase II enzymes that are involved in the
      detoxification of a wide range of carcinogens. The novel GSTA1*A and GSTA1*B
      genetic polymorphism results in differential expression, with lower
      transcriptional activation of GSTA1*B (variant) than that of GSTA1*A (common)
      allele. Considering that cruciferous vegetables induce GSTs, which metabolize
      tobacco smoke carcinogens, we hypothesized that the variant GSTA1*B genotype may
      predispose women to breast cancer, particularly among low cruciferous vegetable
      consumers and among smokers. Thus, we evaluated potential relationships between
      GSTA1 polymorphisms and breast cancer risk, in relation to vegetable consumption
      and smoking status in the Long Island Breast Cancer Study Project (1996-1997), a
      population-based case-control study. Genotyping (1036 cases and 1089 controls)
      was performed, and putative breast cancer risk factors and usual dietary intakes
      were assessed. Having GSTA1*A/*B or *B/*B genotypes was not associated with
      increased breast cancer risk, compared to having the common *A/*A genotype.
      However, among women in the lowest two tertiles of cruciferous vegetable
      consumption, *B/*B genotypes were associated with increased risk (OR (95%
      CI)=1.73 (1.10-2.72) for 0-1 servings/week), compared to women with *A/*A
      genotypes. Among women with *B/*B genotypes, a significant inverse trend between
      cruciferous vegetable consumption and breast cancer risk was observed (P for
      trend=0.05), and higher consumption (4+ servings/week) ameliorated the increased
      risk associated with the genotype. Current smokers with *B/*B genotypes had a
      1.89-fold increase in risk (OR (95% CI)=1.89 (1.09-3.25)), compared with never
      smokers with *A/*A genotypes. These data indicate that GSTA1 genotypes related to
      reduced GSTA1 expression are associated with increased breast cancer primarily
      among women with lower consumption of cruciferous vegetables and among current
      smokers.

PMID- 16624830
TI  - Randomized controlled trial: effects of diet on DNA damage in heavy smokers.
AB  - We have conducted a randomized trial which investigated the ability of dietary
      changes (in particular diets rich in cruciferous vegetables and flavonoids), to
      increase urinary antimutagenicity and inhibit DNA damage in smokers. Ninety heavy
      smokers were recruited and randomly assigned to three groups, and were given
      three different diets. The first diet was based on flavonoid-rich foods,
      particularly cruciferous vegetables, but not based on supplementation; the second
      was a normal isocaloric diet (with an adequate administration of fruits and
      vegetables); and the third was based on supplementation of flavonoids in the form
      of green tea and soy products. DNA adducts were measured by (32)P-postlabelling
      in exfoliated bladder cells at different times since the start of the trial. In
      spite of randomization, subjects in the control group smoked more than those in
      the experimental groups, and this can explain the higher adduct levels at
      baseline. A slight decrease in bulky DNA adducts in exfoliated bladder cells was
      observed after 1 year since the end in the supplementation group and after 1
      month in white blood cells. The only statistically significant association was
      found in a regression model that adjusted for smoking, in which the increase in
      flavonoid intake was associated with a decrease in adducts after 1 year (P =
      0.02). These data suggest that adherence to a diet rich in cruciferous vegetables
      and flavonoids might reduce genotoxicity in the human urinary bladder of smokers,
      but they should be interpreted with caution owing to small numbers and the uneven
      distribution of smoking habits in the experimental groups. Smoking is the most
      important single preventable cause of cancer; at the present stage of knowledge
      it is totally unlikely that certain dietary habits can seriously counteract the
      effects of tobacco smoking.

PMID- 16624831
TI  - Iloprost attenuates doxorubicin-induced cardiac injury in a murine model without
      compromising tumour suppression.
AB  - AIMS: The use of doxorubicin (DOX) as a chemotherapeutic agent is limited by
      cardiac injury. Iloprost, a stable synthetic analogue of prostacyclin, has
      previously been shown to protect against DOX-induced cardiomyocyte injury in
      vitro. Here, we addressed whether iloprost is cardioprotective in vivo and
      whether it compromises the anti-tumour efficacy of DOX. METHODS AND RESULTS:
      Lewis Lung Carcinoma cells were implanted subcutaneously in the flank of C57BL/6
      mice. DOX treatment was commenced from when tumours became visible. Iloprost was
      administered from prior to DOX treatment until sacrifice. Echocardiography and
      invasive haemodynamic measurements were performed immediately before sacrifice.
      As expected, DOX induced cardiac cell apoptosis and cardiac dysfunction, both of
      which were attenuated by iloprost. Also, iloprost alone had no effect on tumor
      growth and indeed, did not alter the DOX-induced suppression of this growth.
      CONCLUSION: In a murine model, iloprost attenuated the acute cardiac injury and
      dysfunction induced by DOX therapy without compromising its chemotherapeutic
      effect.

PMID- 16624832
TI  - Pre-hospital thrombolysis delivered by paramedics is associated with reduced time
      delay and mortality in ambulance-transported real-life patients with ST-elevation
      myocardial infarction.
AB  - AIMS: There are sparse data on the impact of pre-hospital thrombolysis (PHT) in
      real-life patients. We therefore evaluated treatment delays and outcome in a
      large cohort of ambulance-transported real-life patients with ST-elevation
      myocardial infarction (STEMI) according to PHT delivered by paramedics or in
      hospital thrombolysis. METHODS AND RESULTS: Prospective cohort study used data
      from the Swedish Register of Cardiac intensive care on patients admitted to the
      coronary care units of 75 Swedish hospitals in 2001-2004. Ambulance-transported
      thrombolytic-treated patients younger than age 80 with a diagnosis of acute
      myocardial infarction were included. Patients with PHT (n=1690) were younger, had
      a lower prevalence of co-morbid conditions, fewer complications, and a higher
      ejection fraction (EF) than in-hospital-treated patients (n=3685). Median time
      from symptom onset to treatment was 113 min for PHT and 165 min for in-hospital
      thrombolysis. One-year mortality was 7.2 vs. 11.8% for PHT and in-hospital
      thrombolysis, respectively. In a multivariable analysis, after adjusting for
      baseline characteristics and rescue angioplasty, PHT was associated with lower 1
      year mortality (odds ratio 0.71, 0.55-0.92, P=0.008). CONCLUSION: When compared
      with regular in-hospital thrombolysis, pre-hospital diagnosis and thrombolysis
      with trained paramedics in the ambulances are associated with reduced time to
      thrombolysis by almost 1 h and reduced adjusted 1-year mortality by 30% in real
      life STEMI patients.

PMID- 16624833
TI  - ARVC with left ventricular involvement in a young woman.

PMID- 16624834
TI  - Prevalence and impact of worsening renal function in patients hospitalized with
      decompensated heart failure: results of the prospective outcomes study in heart
      failure (POSH).
AB  - AIMS: To determine the prevalence and risk factors for worsening renal function
      (WRF) among patients hospitalized for decompensated heart failure (HF) and the
      association with subsequent re-hospitalization and mortality. METHODS AND
      RESULTS: We prospectively enrolled 299 patients across eight European countries
      (mean age 68, 74% men). HF was defined using the European Society of Cardiology
      criteria, but only patients with a history of ejection fraction < or =40% on
      echocardiography were recruited. WRF was defined as an increase in serum
      creatinine >26 micromol/L ( approximately 0.3 mg/dL) from admission. Follow-up
      was 95% complete to 6 months. Nearly one-third of patients [72 of 248 patients,
      29% (95% CI 26-32%)] developed WRF during hospitalization, excluding patients who
      had a major in-hospital complication likely to compromise renal function. The
      risk of WRF in this group was independently associated with serum creatinine
      levels on admission [odds ratio (OR) 3.02 (95% CI 1.58-5.76)], pulmonary oedema
      [OR 3.35 (1.79-6.27)], and a history of atrial fibrillation [OR 0.35 (0.18
      0.67)]. Although the mortality of WRF patients was not increased significantly,
      the length of stay was 2 days longer [median 11 days (90% range (4-41) vs. 9 days
      (4-34), P=0.006]. The re-hospitalization rate was similar in both groups.
      CONCLUSION: WRF is common in patients admitted to European hospitals with
      decompensated HF. Such patients have longer duration admissions, but a similar
      mortality and re-hospitalization rate to those without WRF (if patients
      experiencing a major in-hospital complication are excluded).

PMID- 16624835
TI  - Should intravenous thrombolysis keep a place in the treatment of acute ST
      elevation myocardial infarction?

PMID- 16624836
TI  - ALDH2 promoter polymorphism has no effect on the risk for alcoholism.
AB  - AIM: To test for the possible association between mitochondrial aldehyde
      dehydrogenase (ALDH2) promoter polymorphism and alcoholism. METHODS: Genotyping
      to identify the polymorphisms in 515 alcoholic patients and 361 normal controls
      was performed. RESULTS: There were no significant differences between the
      genotype and allele frequencies of the -357A/G polymorphism in alcoholics and
      normal controls. Linkage disequilibrium was observed between the promoter and
      exon 12 polymorphisms. CONCLUSION: These results suggest the ALDH2 promoter
      polymorphism does not affect the risk for alcoholism.

PMID- 16624837
TI  - PHosphatidylethanol (PEth) concentrations in blood are correlated to reported
      alcohol intake in alcohol-dependent patients.
AB  - AIMS: Phosphatidylethanol (PEth) is an abnormal phospholipid formed only in the
      presence of ethanol by the enzyme phospholipase D. PEth in blood is a promising
      new marker for ethanol abuse. None of the biological markers used at the present
      time is sensitive and specific enough for the diagnosis of alcoholism. METHODS:
      The most frequently used alcohol markers [carbohydrate deficient transferrin
      (CDT), gamma-glutamyltransferase (GGT), and mean corpuscular volume (MCV)] were
      studied together with PEth in actively drinking alcohol-dependent patients
      (inpatients and outpatients), with regard to correlation to ethanol intake and
      diagnostic sensitivity of the markers. The relation between the markers was also
      studied. RESULTS: PEth, CDT, and GGT correlated to ethanol intake, with the
      strongest correlation found for PEth. The diagnostic sensitivity for PEth was
      99%, and for other markers it varied between 40 and 77%. Only when CDT was
      combined with GGT was a sensitivity of 94% reached. PEth correlated to CDT and
      GGT but not to MCV. CDT did not correlate to GGT or MCV. CONCLUSIONS: Blood
      concentrations of PEth are highly correlated to ethanol intake, and the present
      results indicate that its diagnostic sensitivity is higher than that for
      previously established alcohol markers.

PMID- 16624838
TI  - Attentional bias for alcohol-related information in adolescents with alcohol
      dependent parents.
AB  - AIMS: to assess the attentional bias for alcohol-related information in
      adolescents with (n = 15), and without (n = 15), a parental history of alcohol
      dependence. METHODS: participants completed questionnaires assessing depression,
      weekly alcohol consumption, anxiety, and concerns about alcohol consumption and
      undertook subliminal and supraliminal computerized Stroop tasks using colour
      words, alcohol-related words, and control words. RESULTS: adolescents with
      alcohol-dependent parents showed supraliminal interference for alcohol-related
      words. The magnitude of this interference was correlated with higher trait and
      state anxiety, and lower levels of weekly alcohol consumption. No interference
      was found on the subliminal alcohol Stroop task. CONCLUSIONS: while it is likely
      that this attentional bias for alcohol-related cues reflects the concerns
      regarding parental drinking, it is also possible that this might underlie the
      increased risk of future alcohol dependence in the children of alcohol-dependent
      parents.

PMID- 16624839
TI  - Establishing rates of binge drinking in the UK: anomalies in the data.
AB  - AIMS: Several studies funded by the UK government have been influential in
      understanding rates of 'binge drinking' in the UK. This analysis aims to
      establish consistency between results and clarify UK rates of binge drinking.
      METHOD: The relevant sections of these surveys were compared: the Scottish Health
      Survey (SHS) 1998, the General Household Survey (GHS) 2002, and the Health Survey
      for England (HSE) 2003. In addition the methodology used by the Health Protection
      Agency in the Adult Drinking Patterns in Northern Ireland (2003) was compared
      with the approach used by the SHS, GHS, and HSE. RESULTS: Marked differences were
      observed between the results of the GHS 2002 and both the SHS 1998 and the HSE
      2002 despite each using a similar methodology, with the HSE 2003 reporting a rate
      of 'binge drinking' in young males of 57%, and the GHS reporting a rate of 35%.
      This difference may be largely attributed to variations in the criteria in binge
      drinking in each study. These differences in interpretation do not appear to have
      been acknowledged. Indeed several key documents on alcohol harm reduction made
      inaccurate citations of previous surveys. CONCLUSION: The media rhetoric on
      escalating rates of binge drinking in the UK should be regarded with caution
      until trends are based on standardized recording and reporting.

PMID- 16624840
TI  - Family bonding and adolescent alcohol use: moderating effect of living with
      excessive drinking parents.
AB  - AIMS: Excessive parental drinking has been shown to be positively related to
      adolescent alcohol use and family bonding negatively related. The aim of the
      present study was to determine if the perception of parental drinking moderates
      the relationship between family bonding and adolescent alcohol use. METHODS:
      Linear structural equation models for multiple group comparisons were estimated
      based on a national representative sample of 3,448 eight and ninth graders in
      Switzerland (mean age 14.77; SD 0.89). RESULTS: Adjusted for gender and age, the
      results confirm that strong family bonds were negatively related to both
      frequency of alcohol intake and lifetime frequency of drunkenness. Furthermore, a
      positive link was found with regard to the perception of parental drinking.
      However, the multiple group comparison revealed that the negative relationship
      between bonding and adolescent alcohol use was even stronger among adolescents
      whose parents drink excessively than among those whose parents did not.
      CONCLUSIONS: These results indicate that it may be particularly important for
      parents in the former category to establish strong family bonds (e.g. by spending
      free time with their children, listening to their worries) so as to limit
      adolescent excessive drinking.

PMID- 16624841
TI  - Interaction of homocysteine and conventional predisposing factors on risk of
      ischaemic stroke in young people: consistency in phenotype-disease analysis and
      genotype-disease analysis.
AB  - BACKGROUND AND OBJECTIVES: Whether the association between mild
      hyperhomocysteinaemia and ischaemic stroke is the consequence of a predisposing
      genetic background or is due to the confounding influence of established
      predisposing factors remains to be determined. METHODS: Plasma total homocysteine
      (tHcy) concentration and the distribution of the C677T genotypes of the
      methylenetetrahydrofolate reductase gene (MTHFR) were compared in 174 consecutive
      patients with stroke aged <45 years and 155 age and sex-matched controls. The
      effect of conventional risk factors on the relationship between phenotype-disease
      and genotype-disease was analysed by two-way and three-way interaction analysis
      and by the classification and regression trees (CART) model. RESULTS: tHcy
      concentrations were markedly higher in patients with ischaemic stroke (median
      11.9 micromol/l, range 2.0-94.0) than in controls (median 9.8 micromol/l, range
      4.7-49.6). An increased risk was also associated with the TT677 genotype (odds
      ratio (OR) 1.98; 95% confidence interval (CI) 1.04 to 3.78) and with the T allele
      (1.40; 95% 1.03 to 1.92) of the MTHFR gene. A differential effect of Hcy levels
      on risk of stroke was observed according to the distribution of environmental
      behavioural risk factors, with a stronger influence in the subcategory of people
      with hypertension and smokers (OR 24.8; 95% CI 3.15 to 196). A comparable
      environmental-dependent TT677 MTHFR genotype-stroke association was observed in
      the genotype-disease analysis. CONCLUSIONS: A consistency of phenotype-disease
      analysis and genotype-disease analysis is indicated by analysing specific
      subcategories of patients, defined by the distribution of established risk
      factors. The assumption that the Hcy-stroke relationship is unlikely due to a
      reverse-causality bias is indirectly supported by our data.

PMID- 16624842
TI  - Validation of the nerve axon reflex for the assessment of small nerve fibre
      dysfunction.
AB  - OBJECTIVE: To validate nerve-axon reflex-related vasodilatation as an objective
      method to evaluate C-nociceptive fibre function by comparing it with the standard
      diagnostic criteria. METHODS: Neuropathy was evaluated in 41 patients with
      diabetes (26 men and 15 women) without peripheral vascular disease by assessing
      the Neuropathy Symptom Score, the Neuropathy Disability Score (NDS), the
      vibration perception threshold (VPT), the heat detection threshold (HDT), nerve
      conduction parameters and standard cardiovascular tests. The neurovascular
      response to 1% acetylcholine (Ach) iontophoresis was measured at the forearm and
      at both feet by laser flowmetry. An age-matched and sex-matched control group of
      10 healthy people was also included. RESULTS: Significant correlations were
      observed between the neurovascular response at the foot and HDT (r(s) = -0.658;
      p<0.0001), NDS (r(s) = -0.665; p<0.0001), VPT (r(s) = -0.548; p = 0.0005), tibial
      nerve conduction velocity (r(s) = 0.631; p = 0.0002), sural nerve amplitude (r(s)
      = 0.581; p = 0.0002) and autonomic function tests. According to the NDS, in
      patients with diabetes who had mild, moderate or severe neuropathy, a
      significantly lower neurovascular response was seen at the foot than in patients
      without neuropathy and controls. A neurovascular response <50% was found to be
      highly sensitive (90%), with a good specificity (74%), in identifying patients
      with diabetic neuropathy. CONCLUSION: Small-fibre dysfunction can be diagnosed
      reliably with neurovascular response assessment. This response is already reduced
      in the early stages of peripheral neuropathy, supporting the hypothesis that
      small-fibre impairment is an early event in the natural history of diabetic
      neuropathy.

PMID- 16624843
TI  - DM2 intronic expansions: evidence for CCUG accumulation without flanking sequence
      or effects on ZNF9 mRNA processing or protein expression.
AB  - Myotonic dystrophy type 2 (DM2) is caused by a CCTG expansion mutation in intron
      1 of the zinc finger protein 9 (ZNF9) gene. The mean expansion size in patients
      is larger than for DM1 or any previously reported disorder (mean=5000 CCTGs;
      range=75-11 000), and similar to DM1, repeats containing ribonuclear inclusions
      accumulate in affected DM2 tissue. Although an RNA gain-of-function mechanism
      involving DM1 CUG or DM2 CCUG expansion transcripts is now well established,
      still debated are the potential role that flanking sequences within the DMPK 3'
      UTR may have on disease pathogenesis and whether or not decreased expression of
      DMPK, ZNF9 or neighboring genes at these loci contribute to disease. To address
      these questions in DM2, we have examined the nucleic acid content of the
      ribonuclear inclusions and the effects of these large expansions on ZNF9
      expression. Using cell lines either haploid or homozygous for the expansion, as
      well as skeletal muscle biopsy tissue, we demonstrate that pre-mRNAs containing
      large CCUG expansions are normally spliced and exported from the nucleus, that
      the expansions do not decrease ZNF9 expression at the mRNA or protein level, and
      that the ribonuclear inclusions are enriched for the CCUG expansion, but not
      intronic flanking sequences. These data suggest that the downstream molecular
      effects of the DM2 mutation are triggered by the accumulation of CCUG repeat
      tract alone.

PMID- 16624844
TI  - Defects in articular cartilage metabolism and early arthritis in fibroblast
      growth factor receptor 3 deficient mice.
AB  - Fibroblast growth factor (FGF) receptor 3 has been identified as a key regulator
      of endochondral bone development and of post-natal bone metabolism through its
      action on growth plate chondrocytes and osteoblasts, respectively. It has also
      been shown to promote chondrogenesis and cartilage production by cultured pre
      chondrogenic cells in response to FGF18. In the current studies, we show that the
      absence of signaling through Fgfr3 in the joints of Fgfr3(-/-) mice leads to
      premature cartilage degeneration and early arthritis. Degenerative changes in
      cartilage matrix included excessive proteolysis of aggrecan core protein and type
      II collagen, as measured by neo-epitope immunoreactivity. These changes were
      accompanied by increased expression of metalloproteinase MMP13, type X collagen,
      cellular hypertrophy and loss of proteoglycan at the articular surface. Using a
      novel micro-mechanical indentation protocol, it was shown that articular
      cartilage in the humeral head of 4-month-old Fgfr3(-/-) mice was less resistant
      to compressive force and less stiff than that of littermate controls. These
      results identify Fgfr3 signaling as a potential target for intervention in
      degenerative disorders of cartilage metabolism.

PMID- 16624846
TI  - Predicting germination response to temperature. I. Cardinal-temperature models
      and subpopulation-specific regression.
AB  - BACKGROUND AND AIMS: The purpose of this study was to compare the relative
      accuracy of different thermal-germination models in predicting germination-time
      under constant-temperature conditions. Of specific interest was the assessment of
      shape assumptions associated with the cardinal-temperature germination model and
      probit distribution often used to distribute thermal coefficients among seed
      subpopulations. METHODS: The seeds of four rangeland grass species were
      germinated over the constant-temperature range of 3-38 degrees C and monitored
      for subpopulation variability in germination-rate response. Subpopulation
      specific germination rate was estimated as a function of temperature and residual
      model error for three variations of the cardinal-temperature model, non-linear
      regression and piece-wise linear regression. The data were used to test relative
      model fit under alternative assumptions regarding model shape. KEY RESULTS: In
      general, optimal model fit was obtained by limiting model-shape assumptions. All
      models were relatively accurate in the sub-optimal temperature range except in
      the 3 degrees C treatment where predicted germination times were in error by as
      much as 70 d for the cardinal-temperature models. CONCLUSIONS: Germination model
      selection should be driven by research objectives. Cardinal-temperature models
      yield coefficients that can be directly compared for purposes of screening
      germplasm. Other model formulations, however, may be more accurate in predicting
      germination-time, especially at low temperatures where small errors in predicted
      rate can result in relatively large errors in germination time.

PMID- 16624845
TI  - Parental genome separation and elimination of cells and chromosomes revealed by
      AFLP and GISH analyses in a Brassica carinata x Orychophragmus violaceus cross.
AB  - BACKGROUND AND AIMS: The phenomenon of parental genome separation during the
      mitotic divisions of hybrid cells was proposed to occur under genetic control in
      intergeneric hybrids between cultivated Brassica species and Orychophragmus
      violaceus (2n = 24). To elucidate further the cytological and molecular
      mechanisms behind parental genome separation, Brassica carinata (2n = 34) x O.
      violaceus hybrids were resynthesized and their chromosome/genomic complements
      analysed. METHODS: F(1) hybrids of the cross were obtained following embryo
      rescue, and were investigated for their cytological behaviour and subjected to
      genomic in situ hybridization (GISH) and amplified fragment length polymorphism
      (AFLP) to determine the contribution of parental genomes. KEY RESULTS: All the
      F(1) plants with high fertility closely resembled B. carinata in morphological
      attributes. These were mixoploids with 2n chromosome numbers ranging from 17 to
      35; however, 34, the same number as in B. carinata, was the most frequent number
      of chromosomes in ovary and pollen mother cells (PMCs). GISH clearly identified
      16 chromosomes of B. nigra in ovary cells and PMCs with 2n = 34 and 35. However,
      no O. violaceus chromosome was detected, indicating the presence of the intact B.
      carinata genome and elimination of the entire O. violaceus genome. However, some
      AFLP bands specific for O. violaceus and novel for the two parents were detected
      in the leaves. Cells with fewer than 34 chromosomes had lost some B. oleracea
      chromosomes. F(2) plants were predominantly like B. carinata, but some contained
      O. violaceus characters. CONCLUSIONS: The cytological mechanism for the results
      involves complete and partial genome separation at mitosis in embryos of F(1)
      plants followed by chromosome doubling, elimination of cells with O. violaceus
      chromosomes and some introgression of O. violaceus genetic information.

PMID- 16624847
TI  - Tai Chi versus brisk walking in elderly women.
AB  - PURPOSE: to compare the effects of a short style of Tai Chi versus brisk walking
      training programme on aerobic capacity, heart rate variability (HRV), strength,
      flexibility, balance, psychological status and quality of life in elderly women.
      METHODS: nineteen community-dwelling, sedentary women (aged 71.4 +/- 4.5 years)
      were randomly assigned to Tai Chi Chuan (TCC; n = 11) or brisk walking group
      (BWG; n = 8). A separate group of elderly women was recruited from the same
      population to act as a sedentary comparison group (SCG; n = 8). The exercise
      groups met for 1 h, three days per week for 12 weeks. Outcomes measured before
      and after training included estimated VO2max, spectral analysis of HRV (high
      frequency, low-frequency power as well as high- and low-frequency power in
      normalised units) as a measure of autonomic control of the heart, isometric knee
      extension and handgrip muscle strength, single-leg stance time, the State Trait
      Anxiety Inventory (STAI), Profile of Mood States (POMS) and Short Form-36 (SF-36)
      questionnaires. RESULTS: significant improvement was seen in estimated VO(2)max
      in the TCC group (TCC versus SCG P = 0.003, TCC versus BWG P = 0.08). The mean
      within-person change of high-frequency power in normalised units (HFnu) increased
      [8.2 (0.14-16.3)], representing increased parasympathetic activity, and low
      frequency power in normalised units (LFnu) decreased [-8.7 (-16.8-0.5)],
      representing decreased sympathetic activity, in the TCC group only. Significant
      gains were also seen in the non-dominant knee extensor strength and single-leg
      stance time (TCC versus BWG P < 0.05). CONCLUSIONS: a short style of TCC was
      found to be an effective way to improve many fitness measures in elderly women
      over a 3-month period. TCC was also found to be significantly better than brisk
      walking in enhancing certain measures of fitness including lower extremity
      strength, balance and flexibility.

PMID- 16624848
TI  - Marginal zinc deficiency exacerbates bone lead accumulation and high dietary zinc
      attenuates lead accumulation at the expense of bone density in growing rats.
AB  - Environmental lead exposure is associated with reduced bone growth and quality,
      which may predispose to osteoporosis. Zinc supplementation may reduce lead
      accumulation; however, effects on bone development have not been addressed. Our
      objective was to investigate the effects of marginal zinc (MZ) and supplemental
      zinc (SZ) intakes on bone lead deposition and skeletal development in lead
      exposed rats. In a factorial design, weanling Sprague-Dawley rats were assigned
      to MZ (8 mg/kg diet); zinc-adequate control (CT; 30 mg/kg); zinc-adequate, diet
      restricted (DR; 30 mg/kg); or SZ (300 mg/kg) groups, with and without lead
      acetate-containing drinking water (200 mg Pb/l) for 3 weeks. Excised femurs were
      analyzed for bone mineral density (BMD) by dual-energy x-ray absorptiometry,
      morphometry, and mineral content. MZ had higher femur lead and lower femur zinc
      concentrations and impaired skeletal growth and mineralization than CT. DR
      inhibited growth but did not result in higher femur lead concentrations than CT.
      SZ had higher femur zinc and lower femur lead concentrations than the other
      treatments. DR and SZ had impaired BMD versus CT and MZ. Lead also retarded
      skeletal growth and impaired BMD, but an interaction between lead and MZ was only
      found for femoral knee width, which was lower in MZ exposed to lead. In summary,
      while MZ deficiency exacerbated bone lead concentration, it generally did not
      intensify lead toxicity. SZ was protective against bone lead but was detrimental
      to BMD, suggesting that the optimal level of SZ to reduce lead absorption, while
      supporting growth and bone development, requires further investigation.

PMID- 16624849
TI  - Tissue manganese concentrations in young male rhesus monkeys following subchronic
      manganese sulfate inhalation.
AB  - High-dose human exposure to manganese results in manganese accumulation in the
      basal ganglia and dopaminergic neuropathology. Occupational manganese
      neurotoxicity is most frequently linked with manganese oxide inhalation; however,
      exposure to other forms of manganese may lead to higher body burdens. The
      objective of this study was to determine tissue manganese concentrations in
      rhesus monkeys following subchronic (6 h/day, 5 days/week) manganese sulfate
      (MnSO(4)) inhalation. A group of monkeys were exposed to either air or MnSO(4)
      (0.06, 0.3, or 1.5 mg Mn/m(3)) for 65 exposure days before tissue analysis.
      Additional monkeys were exposed to MnSO(4) at 1.5 mg Mn/m(3) for 15 or 33
      exposure days and evaluated immediately thereafter or for 65 exposure days
      followed by a 45- or 90-day delay before evaluation. Tissue manganese
      concentrations depended upon the aerosol concentration, exposure duration, and
      tissue. Monkeys exposed to MnSO(4) at > or = 0.06 mg Mn/m(3) for 65 exposure days
      or to MnSO(4) at 1.5 mg Mn/m(3) for > or = 15 exposure days developed increased
      manganese concentrations in the olfactory epithelium, olfactory bulb, olfactory
      cortex, globus pallidus, putamen, and cerebellum. The olfactory epithelium,
      olfactory bulb, globus pallidus, caudate, putamen, pituitary gland, and bile
      developed the greatest relative increase in manganese concentration following
      MnSO(4) exposure. Tissue manganese concentrations returned to levels observed in
      the air-exposed animals by 90 days after the end of the subchronic MnSO(4)
      exposure. These results provide an improved understanding of MnSO(4) exposure
      conditions that lead to increased concentrations of manganese within the nonhuman
      primate brain and other tissues.

PMID- 16624851
TI  - Three-generation evaluation of dietary para-nonylphenol in CD (Sprague-Dawley)
      rats.
AB  - This study evaluated the potential for dietary para-nonylphenol (NP; CAS No.
      84852-15-3) to affect parental fertility and growth and development of three
      offspring generations in CD (Sprague-Dawley [SD]) rats, including sperm counts
      across generations to determine the validity of equivocal reductions observed in
      the F2 generation by R. E. Chapin et al. (1999, Toxicol. Sci. 52, 80-91). Male
      rat kidney toxicity was also examined based on inconsistent observations in NP
      exposed rats at 2000 ppm but not at 200 or 650 ppm in Purina 5002 (H. C. Cunny et
      al., 1997, Regul. Toxicol. Pharmacol. 26, 172-178) and at all of these NP
      concentrations in NIH-07 diet (R. E. Chapin et al., 1999, Toxicol. Sci. 52, 80
      91). Concentrations were 0, 20, 200, 650, and 2000 ppm NP in Purina 5002 diet and
      0 and 650 ppm NP in NIH-07 diet. 17beta-estradiol (E2) was used as a positive
      control at 2.5 ppm in Purina 5002 diet. There were no NP effects on any
      reproductive parameters in any generation, including sperm counts. Kidney
      toxicity (histopathology) occurred at 650 and 2000 ppm with no clear difference
      for the two diets. Ovarian weight was decreased at 2000 ppm NP in all
      generations, with no effect on reproduction. Dietary E2 at 2.5 ppm caused renal,
      reproductive, and developmental (lactational and peripubertal) toxicity in all
      generations. This study confirmed that dietary NP is not a selective reproductive
      toxicant with an no observable adverse effect level (NOAEL) of > 2000 ppm (
      approximately > 150 mg/kg/day) and provided an NOAEL for male rat kidney toxicity
      of 200 ppm NP (approximately 15 mg/kg/day).

PMID- 16624850
TI  - Thimerosal induces apoptosis in a neuroblastoma model via the cJun N-terminal
      kinase pathway.
AB  - The cJun N-terminal kinase (JNK)-signaling pathway is activated in response to a
      variety of stimuli, including environmental insults, and has been implicated in
      neuronal apoptosis. In this study, we investigated the role that the JNK pathway
      plays in neurotoxicity caused by thimerosal, an ethylmercury-containing
      preservative. SK-N-SH cells treated with thimerosal (0-10 microM) showed an
      increase in the phosphorylated (active) form of JNK and cJun with 5 and 10 microM
      thimerosal treatment at 2 and 4 h. To examine activator protein-1 (AP-1)
      transcription, cells were transfected with a pGL2 vector containing four AP-1
      consensus sequences and then treated with thimerosal (0-2.5 microM) for 24 h.
      Luciferase studies showed an increase in AP-1 transcriptional activity upon
      thimerosal administration. To determine the components of the AP-1 complex, cells
      were transfected with a dominant negative to either cFos (A-Fos) or cJun (TAM67).
      Reporter analysis showed that TAM67, but not A-Fos, decreased AP-1
      transcriptional activity, indicating a role for cJun in this pathway. To assess
      which components are essential to apoptosis, cells were treated with a cell
      permeable JNK inhibitor II (SP600125) or transfected with TAM67, and the
      downstream effectors of apoptosis were analyzed. Cells pretreated with SP600125
      showed decreases in activation of caspases 9 and 3, decreases in degradation of
      poly(ADP-ribose) polymerase (PARP), and decreased levels of proapoptotic Bim, in
      comparison to cells treated with thimerosal alone. However, cells transfected
      with TAM67 showed no changes in those same components. Taken together, these
      results indicate that thimerosal-induced neurotoxicity occurs through the JNK
      signaling pathway, independent of cJun activation, leading ultimately to
      apoptotic cell death.

PMID- 16624852
TI  - A regression spline model for developmental toxicity data.
AB  - Observed dose-response patterns of data from several developmental toxicity
      experiments appear to be nonlinear and should be characterized by an appropriate
      model to adequately fit this observed pattern. Information from these animal
      studies of ambient substances that are noncarcinogenic, yet potentially toxic, to
      humans is used by federal protection agencies (Environmental Protection Agency,
      Occupational Safety and Health Administration, Food and Drug Administration) to
      determine safe exposure levels, such as no observed adverse effects level and
      benchmark dose. We have developed a flexible regression linear B-spline model for
      application to developmental toxicity dose-response data from animal studies of
      these noncarcinogens. We apply our model to data from two CD-1 mice studies of
      the National Toxicology Program; the observed dose-response pattern from both
      appears nonlinear: (1) experiment of 131 pregnant mice allocated over five
      exposure levels (0, 0.025, 0.05, 0.10, and 0.15% diet) of diethylhexyl phthalate
      and (2) experiment of 111 pregnant mice exposed to five levels (0, 62.5, 125,
      250, and 500 mg/kg/day) of diethylene glycol dimethyl ether. In each study, we
      measure litter response as the proportion of adversely affected fetuses. Upon
      applying our B-spline model to the data from both studies, we predict nonlinear
      dose-response, with improvement over the more typical logistic dose-response
      model in each of the two studies.

PMID- 16624853
TI  - Maintenance of mammalian enteric nervous system progenitors by SOX10 and
      endothelin 3 signalling.
AB  - The transcriptional regulator SOX10 and the signalling molecule endothelin 3 have
      important roles in the development of the mammalian enteric nervous system (ENS).
      Using a clonal cell culture system, we show that SOX10 inhibits overt neuronal
      and glial differentiation of multilineage ENS progenitor cells (EPCs), without
      interfering with their neurogenic commitment. We also demonstrate that endothelin
      3 inhibits reversibly the commitment and differentiation of EPCs along the
      neurogenic and gliogenic lineages, suggesting a role for this factor in the
      maintenance of multilineage ENS progenitors. Consistent with such a role, the
      proportion of Sox10-expressing progenitors in the total population of enteric
      neural crest cells is reduced in the gut of endothelin 3-deficient embryos. This
      reduction may be related to the requirement of endothelin signalling for the
      proliferation of ENS progenitors. The dependence of ENS progenitors on endothelin
      3 is more pronounced at the migratory front of enteric neural crest cells, which
      is associated with relatively high levels of endothelin 3 mRNA. Our findings
      indicate that SOX10 and endothelin 3 have a crucial role in the maintenance of
      multilineage enteric nervous system progenitors.

PMID- 16624854
TI  - Distinct cardiac malformations caused by absence of connexin 43 in the neural
      crest and in the non-crest neural tube.
AB  - Connexin 43 (Cx43) is expressed in the embryonic heart, cardiac neural crest
      (CNC) and neural tube, and germline knockout (KO) of Cx43 results in aberrant
      cardiac outflow tract (OFT) formation and abnormal coronary deployment. Prior
      studies suggest a vital role for CNC expression of Cx43 in heart development.
      Surprisingly, we found that conditional knockout (CKO) of Cx43 in the dorsal
      neural tube and CNC mediated by Wnt1-Cre failed to recapitulate the Cx43-null OFT
      phenotype, although coronary vasculature was abnormal in this mutant line. A
      broader CKO mediated by P3pro (Pax3)-Cre, involving both ventral and dorsal
      aspects of the thoracic neural tube and CNC, resulted in infundibular bulging and
      coronary anomalies similar to those seen in germline Cx43-null hearts. P3pro-Cre
      mediated loss of Cx43 in the neural tube was characterized by a late phase of
      cellular delamination from the dorsal and lateral neural tube, a markedly
      increased abundance of neuroepithelium-derived cells outside of the neural tube
      and an excess of such cells infiltrating the heart and infundibulum. Thus,
      expression of Cx43 in the CNC is crucial for normal coronary deployment, but Cx43
      is not required in the CNC for normal OFT morphogenesis. Rather, this study
      suggests a novel function for Cx43 in which Cx43 acts through non-crest
      neuroepithelial cells to suppress cellular delamination from the neural tube and
      thereby preserve normal OFT development.

PMID- 16624855
TI  - The TAGteam DNA motif controls the timing of Drosophila pre-blastoderm
      transcription.
AB  - The Drosophila sex-determination switch gene Sex-lethal (Sxl) and the X
      chromosome signal element genes (XSEs) that induce the female-specific expression
      of Sxl are transcribed extremely early in development when most of the genome of
      this organism is still silent. The DNA sequence CAGGTAG had been implicated in
      this pre-cellular blastoderm activation of sex-determination genes. A genome-wide
      computational search, reported here, suggested that CAGGTAG is not specific to
      early sex-determination genes, since it is over-represented upstream of most
      genes that are transcribed pre-cellular blastoderm, not just those involved in
      sex determination. The same search identified similarly over-represented, one
      base-pair degenerate sequences as possible functional synonyms of CAGGTAG. We
      call these heptamers collectively, the TAGteam. Relevance of the TAGteam
      sequences to pre-cellular blastoderm transcription was established through
      analysis of TAGteam changes in Sxl, scute (an XSE), and the ;ventral repression
      element' of the pattern-formation gene zerknullt. Decreasing the number of
      TAGteam sites retarded the onset of pre-blastoderm transcription, whereas
      increasing their number correlated with an advanced onset. Titration of
      repressors was thought to be the rate-limiting step determining the onset of such
      early transcription, but this TAGteam dose effect shows that activators must also
      play an important role in the timing of pre-blastoderm gene expression.

PMID- 16624856
TI  - Senseless physically interacts with proneural proteins and functions as a
      transcriptional co-activator.
AB  - The zinc-finger transcription factor Senseless is co-expressed with basic helix
      loop-helix (bHLH) proneural proteins in Drosophila sensory organ precursors and
      is required for their normal development. High levels of Senseless synergize with
      bHLH proteins and upregulate target gene expression, whereas low levels of
      Senseless act as a repressor in vivo. However, the molecular mechanism for this
      dual role is unknown. Here, we show that Senseless binds bHLH proneural proteins
      via its core zinc fingers and is recruited by proneural proteins to their target
      enhancers to function as a co-activator. Some point mutations in the Senseless
      zinc-finger region abolish its DNA-binding ability but partially spare the
      ability of Senseless to synergize with proneural proteins and to induce sensory
      organ formation in vivo. Therefore, we propose that the structural basis for the
      switch between the repressor and co-activator functions of Senseless is the
      ability of its core zinc fingers to interact physically with both DNA and bHLH
      proneural proteins. As Senseless zinc fingers are approximately 90% identical to
      the corresponding zinc fingers of its vertebrate homologue Gfi1, which is thought
      to cooperate with bHLH proteins in several contexts, the Senseless/bHLH
      interaction might be evolutionarily conserved.

PMID- 16624857
TI  - Basonuclin: a novel mammalian maternal-effect gene.
AB  - Basonuclin is a zinc-finger protein found in abundance in oocytes. It qualifies
      as a maternal-effect gene because the source of pre-implantation embryonic
      basonuclin is maternal. Using a transgenic-RNAi approach, we knocked down
      basonuclin specifically in mouse oocytes, which led to female sub-fertility.
      Basonuclin deficiency in oocytes perturbed both RNA polymerase I- and II-mediated
      transcription, and oocyte morphology was affected (as evidenced by cytoplasmic
      and cell surface abnormalities). Some of the affected oocytes, however, could
      still mature to and arrest at metaphase II, and be ovulated. Nevertheless,
      fertilized basonuclin-deficient eggs failed to develop beyond the two-cell stage,
      and this pre-implantation failure accounted for the sub-fertility phenotype.
      These results suggest that basonuclin is a new member of the mammalian maternal
      effect genes and, interestingly, differs from the previously reported mammalian
      maternal-effect genes in that it also apparently perturbs oogenesis.

PMID- 16624858
TI  - Mutation of an upstream cleavage site in the BMP4 prodomain leads to tissue
      specific loss of activity.
AB  - ProBMP4 is initially cleaved at a site adjacent to the mature ligand (the S1
      site) allowing for subsequent cleavage at an upstream (S2) site. Mature BMP4
      synthesized from a precursor in which the S2 site cannot be cleaved remains in a
      complex with the prodomain that is targeted for lysosomal degradation, and is
      thus less active when overexpressed in Xenopus. Here we report that mice carrying
      a point mutation that prevents S2 processing show severe loss of BMP4 activity in
      some tissues, such as testes and germ cells, whereas other tissues that are
      sensitive to Bmp4 dosage, such as the limb, dorsal vertebrae and kidney, develop
      normally. In a haploinsufficient background, inability to cleave the S2 site
      leads to embryonic and postnatal lethality due to defects in multiple organ
      systems including the allantois, placental vasculature, ventral body wall, eye
      and heart. These data demonstrate that cleavage of the S2 site is essential for
      normal development and, more importantly, suggest that this site might be
      selectively cleaved in a tissue-specific fashion. In addition, these studies
      provide the first genetic evidence that BMP4 is required for dorsal vertebral
      fusion and closure of the ventral body wall.

PMID- 16624859
TI  - Mesoderm progenitor cells of common origin contribute to the head musculature and
      the cardiac outflow tract.
AB  - During early embryogenesis, heart and skeletal muscle progenitor cells are
      thought to derive from distinct regions of the mesoderm (i.e. the lateral plate
      mesoderm and paraxial mesoderm, respectively). In the present study, we have
      employed both in vitro and in vivo experimental systems in the avian embryo to
      explore how mesoderm progenitors in the head differentiate into both heart and
      skeletal muscles. Using fate-mapping studies, gene expression analyses, and
      manipulation of signaling pathways in the chick embryo, we demonstrate that cells
      from the cranial paraxial mesoderm contribute to both myocardial and endocardial
      cell populations within the cardiac outflow tract. We further show that Bmp
      signaling affects the specification of mesoderm cells in the head: application of
      Bmp4, both in vitro and in vivo, induces cardiac differentiation in the cranial
      paraxial mesoderm and blocks the differentiation of skeletal muscle precursors in
      these cells. Our results demonstrate that cells within the cranial paraxial
      mesoderm play a vital role in cardiogenesis, as a new source of cardiac
      progenitors that populate the cardiac outflow tract in vivo. A deeper
      understanding of mesodermal lineage specification in the vertebrate head is
      expected to provide insights into the normal, as well as pathological, aspects of
      heart and craniofacial development.

PMID- 16624860
TI  - Aneugenic activity of Op18/stathmin is potentiated by the somatic Q18-->e
      mutation in leukemic cells.
AB  - Op18/stathmin (Op18) is a phosphorylation-regulated microtubule destabilizer that
      is frequently overexpressed in tumors. The importance of Op18 in malignancy was
      recently suggested by identification of a somatic Q18-->E mutation of Op18 in an
      adenocarcinoma. We addressed the functional consequences of aberrant Op18
      expression in leukemias by analyzing the cell cycle of K562 cells either depleted
      of Op18 by expression of interfering hairpin RNA or induced to express wild-type
      or Q18E substituted Op18. We show here that although Op18 depletion increases
      microtubule density during interphase, the density of mitotic spindles is
      essentially unaltered and cells divide normally. This is consistent with
      phosphorylation-inactivation of Op18 during mitosis. Overexpression of wild-type
      Op18 results in aneugenic activities, manifest as aberrant mitosis,
      polyploidization, and chromosome loss. One particularly significant finding was
      that the aneugenic activity of Op18 was dramatically increased by the Q18-->E
      mutation. The hyperactivity of mutant Op18 is apparent in its unphosphorylated
      state, and this mutation also suppresses phosphorylation-inactivation of the
      microtubule-destabilizing activity of Op18 without any apparent effect on its
      phosphorylation status. Thus, although Op18 is dispensable for mitosis, the
      hyperactive Q18-->E mutant, or overexpressed wild-type Op18, exerts aneugenic
      effects that are likely to contribute to chromosomal instability in tumors.

PMID- 16624861
TI  - Rtn1p is involved in structuring the cortical endoplasmic reticulum.
AB  - The endoplasmic reticulum (ER) contains both cisternal and reticular elements in
      one contiguous structure. We identified rtn1Delta in a systematic screen for
      yeast mutants with altered ER morphology. The ER in rtn1Delta cells is
      predominantly cisternal rather than reticular, yet the net surface area of ER is
      not significantly changed. Rtn1-green fluorescent protein (GFP) associates with
      the reticular ER at the cell cortex and with the tubules that connect the
      cortical ER to the nuclear envelope, but not with the nuclear envelope itself.
      Rtn1p overexpression also results in an altered ER structure. Rtn proteins are
      found on the ER in a wide range of eukaryotes and are defined by two membrane
      spanning domains flanking a conserved hydrophilic loop. Our results suggest that
      Rtn proteins may direct the formation of reticulated ER. We independently
      identified Rtn1p in a proteomic screen for proteins associated with the exocyst
      vesicle tethering complex. The conserved hydophilic loop of Rtn1p binds to the
      exocyst subunit Sec6p. Overexpression of this loop results in a modest
      accumulation of secretory vesicles, suggesting impaired exocyst function. The
      interaction of Rtn1p with the exocyst at the bud tip may trigger the formation of
      a cortical ER network in yeast buds.

PMID- 16624862
TI  - Stat-mediated signaling induced by type I and type II interferons (IFNs) is
      differentially controlled through lipid microdomain association and clathrin
      dependent endocytosis of IFN receptors.
AB  - Type I (alpha/beta) and type II (gamma) interferons (IFNs) bind to distinct
      receptors, although they activate the same signal transducer and activator of
      transcription, Stat1, raising the question of how signal specificity is
      maintained. Here, we have characterized the sorting of IFN receptors (IFN-Rs) at
      the plasma membrane and the role it plays in IFN-dependent signaling and
      biological activities. We show that both IFN-alpha and IFN-gamma receptors are
      internalized by a classical clathrin- and dynamin-dependent endocytic pathway.
      Although inhibition of clathrin-dependent endocytosis blocked the uptake of IFN
      alpha and IFN-gamma receptors, this inhibition only affected IFN-alpha-induced
      Stat1 and Stat2 signaling. Furthermore, the antiviral and antiproliferative
      activities induced by IFN-alpha but not IFN-gamma were also affected. Finally, we
      show that, unlike IFN-alpha receptors, activated IFN-gamma receptors rapidly
      become enriched in plasma membrane lipid microdomains. We conclude that IFN-R
      compartmentalization at the plasma membrane, through clathrin-dependent
      endocytosis and lipid-based microdomains, plays a critical role in the signaling
      and biological responses induced by IFNs and contributes to establishing
      specificity within the Jak/Stat signaling pathway.

PMID- 16624863
TI  - A distant coilin homologue is required for the formation of cajal bodies in
      Arabidopsis.
AB  - Cajal bodies (CBs) are subnuclear bodies that are widespread in eukaryotes, being
      found in mammals, many other vertebrates and in all plant species so far
      examined. They are mobile structures, moving, fusing, and budding within the
      nucleus. Here we describe a screen for Arabidopsis mutants with altered CBs and
      describe mutants that have smaller Cajal bodies (ncb-2, ncb-3), lack them
      altogether (ncb-1), have increased numbers of CBs (pcb) or have flattened CBs
      (ccb). We have identified the gene affected in the ncb mutants as a distant
      homolog of the vertebrate gene that encodes coilin (At1g13030) and have termed
      the resulting protein Atcoilin. A T-DNA insertional mutant in this gene (ncb-4)
      also lacks Cajal bodies. Overexpression of Atcoilin cDNA in ncb-1 restores Cajal
      bodies, which recruit U2B'' as in the wild type, but which are, however, much
      larger than in the wild type. Thus we have shown that At1g13030 is required for
      Cajal body formation in Arabidopsis, and we hypothesize that the level of its
      expression is correlated with Cajal body size. The Atcoilin gene is unaffected in
      pcb and ccb, suggesting that other genes can also affect CBs.

PMID- 16624864
TI  - Forced dimerization of gp130 leads to constitutive STAT3 activation, cytokine
      independent growth, and blockade of differentiation of embryonic stem cells.
AB  - The mode of activation of glycoprotein 130 kDa (gp130) and the transmission of
      the activation status through the plasma membrane are incompletely understood. In
      particular, the molecular function of the three juxtamembrane fibronectin III
      like domains of gp130 in signal transmission remains unclear. To ask whether
      forced dimerization of gp130 is sufficient for receptor activation, we replaced
      the entire extracellular portion of gp130 with the c-jun leucine zipper region in
      the chimeric receptor protein L-gp130. On expression in cells, L-gp130 stimulates
      ligand-independent signal transducer and activator of transcription (STAT) 3 and
      extracellular signal-regulated kinase 1/2 phosphorylation. gp130 activation could
      be abrogated by the addition of a competing peptide comprising the leucine zipper
      region of c-fos. When stably expressed in the interleukin-3-dependent Ba/F3
      murine pre-B-cells, these cells showed constitutive STAT3 activation and cytokine
      independent growth over several months. Because gp130 stimulation completely
      suppressed differentiation of murine embryonic stem cells in vitro, we also
      stably expressed L-gp130 in these cells, which completely blocked their
      differentiation in the absence of cytokine stimulation and was consistent with
      high constitutive expression levels of the stem cell factor OCT-4. Thus, L-gp130
      can be used in vitro and in vivo to mimic constitutive and ligand-independent
      activation of gp130 and STAT3, the latter of which is frequently observed in
      neoplastic diseases.

PMID- 16624865
TI  - Phosphoinositide-3 kinase-Rac1-c-Jun NH2-terminal kinase signaling mediates
      collagen I-induced cell scattering and up-regulation of N-cadherin expression in
      mouse mammary epithelial cells.
AB  - During epithelial-to-mesenchymal transitions (EMTs), cells must change their
      interactions with one another and with their extracellular matrix in a
      synchronized manner. To characterize signaling pathways cells use to coordinate
      these changes, we used NMuMG mammary epithelial cells. We showed that these cells
      become fibroblastic and scattered, with increased N-cadherin expression when
      cultured on collagen I. Rac1 and c-Jun NH2-terminal kinase (JNK) were activated
      when cells were plated on collagen I, and dominant inhibitory Rac1 (RacN17) or
      inhibition of JNK signaling prevented collagen I-induced morphological changes
      and N-cadherin up-regulation. Furthermore, inhibiting phosphoinositide-3 kinase
      (PI3K) activity prevented Rac1 and JNK activation as well as collagen I-induced N
      cadherin up-regulation. These data implicate PI3K-Rac1-JNK signaling in collagen
      I-induced changes in NMuMG cells. To establish a role for N-cadherin in collagen
      I-induced cell scattering, we generated N-cadherin overexpressing and knockdown
      NMuMG cells and showed that knocking down N-cadherin expression prevented
      collagen I-induced morphological changes. Motility assays showed that cells
      overexpressing N-cadherin were significantly more motile than mock-transfected
      cells and that N-cadherin-mediated motility was collagen I dependent. In
      addition, we showed that cord formation and branching in three-dimensional
      culture (EMT-dependent events) required N-cadherin expression and PI3K-Rac1-JNK
      signaling.

PMID- 16624866
TI  - A conserved organization of transcription during embryonic stem cell
      differentiation and in cells with high C value.
AB  - Although we have detailed information on the alterations occurring in steady
      state levels of all cellular mRNAs during differentiation, we still know little
      about more global changes. Therefore, we investigated the numbers of molecules of
      RNA polymerase II that are active--and the way those molecules are organized--as
      two mouse cells (aneuploid F9 teratocarcinoma, and euploid and totipotent
      embryonic stem cells) differentiate into parietal endoderm. Quantitative
      immunoblotting shows the number of active molecules roughly halves. Transcription
      sites (detected by light and electron microscopy after allowing engaged
      polymerases to extend nascent transcripts in bromouridine-triphosphate) are
      uniformly distributed throughout the nucleoplasm. The numbers of such sites fall
      during differentiation as nuclei become smaller, but site density and diameter
      remain roughly constant. Similar site densities and diameters are found in
      salamander (amphibian) cells with 11-fold larger genomes, and in aneuploid HeLa
      cells. We conclude that active polymerases and their nascent transcripts are
      concentrated in a limited number of discrete nucleoplasmic sites or factories,
      and we speculate that the organization of transcription is conserved during both
      differentiation and evolution to a high C value.

PMID- 16624867
TI  - Muc4-ErbB2 complex formation and signaling in polarized CACO-2 epithelial cells
      indicate that Muc4 acts as an unorthodox ligand for ErbB2.
AB  - Muc4 serves as an intramembrane ligand for the receptor tyrosine kinase ErbB2.
      The time to complex formation and the stoichiometry of the complex were
      determined to be <15 min and 1:1 by analyses of Muc4 and ErbB2 coexpressed in
      insect cells and A375 tumor cells. In polarized CACO-2 cells, Muc4 expression
      causes relocalization of ErbB2, but not its heterodimerization partner ErbB3, to
      the apical cell surface, effectively segregating the two receptors. The apically
      located ErbB2 is phosphorylated on tyrosines 1139 and 1248. The phosphorylated
      ErbB2 in CACO-2 cells recruits the cytoplasmic adaptor protein Grb2, consistent
      with previous studies showing phosphotyrosine 1139 to be a Grb2 binding site. To
      address the issue of downstream signaling from apical ErbB2, we analyzed the
      three MAPK pathways of mammalian cells, Erk, p38, and JNK. Consistent with the
      more differentiated phenotype of the CACO-2 cells, p38 phosphorylation was
      robustly increased by Muc4 expression, with a consequent activation of Akt. In
      contrast, Erk and JNK phosphorylation was not changed. The ability of Muc4 to
      segregate ErbB2 and other ErbB receptors and to alter downstream signaling
      cascades in polarized epithelial cells suggests that it has a role in regulating
      ErbB2 in differentiated epithelia.

PMID- 16624869
TI  - Neurotoxic pyridinium metabolites of haloperidol are substrates of human organic
      cation transporters.
AB  - Two neurotoxic pyridinium metabolites of haloperidol, 4-(4-chlorophenyl)-1-[4-(4
      fluorophenyl)-4-oxybutyl]pyridinium ion (HPP(+)) and 4-(4-(chlorophenyl)-1-4
      (fluorophenyl)-4-hydroxybutyl-pyridinium (RHPP(+)), are formed in the liver and
      found in the brain. To understand how these neurotoxic pyridinium metabolites are
      distributed in the brain, HPP(+) and RHPP(+) were evaluated as substrates for
      human organic cation transporters (hOCTs). Both HPP(+) and RHPP(+) were
      accumulated in Caco-2 cells, and these accumulations were significantly inhibited
      by pretreatment with the hOCT inhibitors verapamil, cimetidine, phenoxybenzamine,
      and corticosterone. The contribution of each hOCT was evaluated based on
      measurements of the intracellular concentrations of haloperidol metabolites in
      Madin Darby canine kidney (MDCK) cells transfected with hOCT1, hOCT2, or hOCT3.
      HPP(+) accumulated in hOCT-overexpressing MDCK cells in a concentration-dependent
      manner, with estimated K(m) values of 0.99, 2.79, and 2.23 microM and V(max)
      values of 282.1, 256.1, and 400.2 pmol/min/microg protein for hOCT1, hOCT2, and
      hOCT3, respectively. RHPP(+) accumulated in hOCT1- and hOCT3-overexpressing MDCK
      cells, with estimated K(m) values of 5.15 and 8.21 microM and V(max) values of
      1230.9 and 1348.6 pmol/min/microg protein for hOCT1 and hOCT3, respectively. On
      the other hand, RHPP(+) did not accumulate in the hOCT2-expressing MDCK cells.
      These results suggest that HPP(+) and RHPP(+) are substrates for hOCTs, with the
      exception of RHPP(+) for hOCT2. Thus, hOCTs seem to contribute to the disposition
      of these toxic metabolites in human subjects, although further in vivo studies
      are required to elucidate the involvement of hOCTs in the disposition of
      haloperidol pyridinium metabolites.

PMID- 16624868
TI  - On and off membrane dynamics of the endoplasmic reticulum-golgi tethering factor
      p115 in vivo.
AB  - The mechanisms regulating membrane recruitment of the p115 tethering factor in
      vivo are unknown. Here, we describe cycling of p115 between membranes and cytosol
      and document the effects of Golgi matrix proteins, Rab1, and soluble N
      ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors
      (SNAREs) on this process. Rapid membrane/cytosol exchange is shown by swift (t1/2
      approximately 20 s) loss of Golgi-localized p115-green fluorescent protein (GFP)
      after repeated photobleaching of cell periphery and rapid (t1/2 approximately 13
      s) fluorescence recovery after photobleaching Golgi-localized p115-GFP. p115
      mutant missing the GM130/giantin binding site exhibits analogous fluorescence
      recovery after photobleaching (FRAP) (t1/2 approximately 13 s), suggesting that
      GM130 and giantin are not major determinants of p115 membrane dynamics. In
      contrast, p115-GFP exchanges more rapidly (t1/2 approximately 8 s) in cells
      expressing the inactive Rab1/N121I mutant, indicating that p115 cycling is
      influenced by Rab1. p115-GFP dynamics is also influenced by the assembly status
      of SNAREs. In cells expressing an ATPase-deficient NSF/E329Q mutant that inhibits
      SNARE complex disassembly, the cycling kinetics of p115-GFP are significantly
      slower (t1/2 approximately 21 s). In contrast, in cells incubated at reduced
      temperature (10 degrees C) that inhibits vesicular traffic, the cycling kinetics
      of p115-GFP are faster (t1/2 approximately 7 s). These data suggest that p115
      binding sites on the membrane are provided by unassembled SNAREs. In agreement,
      biochemical studies show increased p115 recruitment to membranes in the presence
      of NSF and alpha-SNAP. Our data support a model in which recruitment of tethers
      is directly regulated by the assembly status of SNAREs.

PMID- 16624870
TI  - Pharmacokinetics of atorvastatin and its hydroxy metabolites in rats and the
      effects of concomitant rifampicin single doses: relevance of first-pass effect
      from hepatic uptake transporters, and intestinal and hepatic metabolism.
AB  - Pharmacokinetic coadministration experiments with atorvastatin (ATV) and
      rifampicin (RIF) in rats were performed to investigate the potential involvement
      of hepatic uptake transporters, Oatps (organic anion-transporting polypeptides),
      during hepatic drug elimination, as an in vivo extension of our recently
      published cellular and isolated perfused liver studies. ATV was administered
      orally (10 mg/kg) and intravenously (2 mg/kg) to rats in the absence and presence
      of a single intravenous dose of RIF (20 mg/kg), and pharmacokinetic parameters
      were compared between control and RIF-treatment groups. RIF markedly increased
      the plasma concentrations of ATV and its metabolites when ATV was administered
      orally. The area under the plasma concentration-time curve (AUC(0-infinity)) for
      ATV also increased significantly after intravenous dosing of ATV with RIF, but
      the extent was much less than that observed for oral ATV dosing. Significant
      increases in plasma levels were observed for both metabolites as well. The 7-fold
      higher AUC ratio of metabolites to parent drug following oral versus intravenous
      ATV dosing suggests that ATV undergoes extensive gut metabolism. Both hepatic and
      intestinal metabolism contribute to the low oral bioavailability of ATV in rats.
      In the presence of RIF, the liver metabolic extraction was significantly reduced,
      most likely because of RIF's inhibition on Oatp-mediated uptake, which leads to
      reduced hepatic amounts of parent drug for subsequent metabolism. Gut extraction
      was also significantly reduced, but we were unable to elucidate the mechanism of
      this effect because intravenous RIF caused gut changes in availability. These
      studies reinforce our hypothesis that hepatic uptake is a major contributor to
      the elimination of ATV and its metabolites in vivo.

PMID- 16624871
TI  - Involvement of transporters in the hepatic uptake and biliary excretion of
      valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans.
AB  - Valsartan is a highly selective angiotensin II AT1-receptor antagonist for the
      treatment of hypertension. Valsartan is mainly excreted into the bile in
      unchanged form. Because valsartan has an anionic carboxyl group, we hypothesized
      that a series of organic anion transporters could be involved in its hepatic
      clearance. In this study, to identify transporters that mediate the hepatic
      uptake and biliary excretion of valsartan and estimate the contribution of each
      transporter to the overall hepatic uptake and efflux, we characterized its
      transport using transporter-expressing systems, human cryopreserved hepatocytes,
      and Mrp2-deficient Eisai hyperbilirubinemic rats (EHBRs). Valsartan was
      significantly taken up into organic anion-transporting polypeptide (OATP) 1B1
      (OATP2/OATP-C)- and OATP1B3 (OATP8)-expressing HEK293 cells. We also observed
      saturable uptake into human hepatocytes. Based on our estimation, the relative
      contribution of OATP1B1 to the uptake of valsartan in human hepatocytes depends
      on the batch, ranging from 20 to 70%. Regarding efflux transporters, the ratio of
      basal-to-apical transcellular transport of valsartan to that in the opposite
      direction in OATP1B1/MRP2 (multidrug resistance-associated protein 2) double
      transfected cells was the highest among the three kinds of double transfectants,
      OATP1B1/MRP2, OATP1B1/multi-drug resistance 1, and OATP1B1/breast cancer
      resistance protein-expressing MDCKII cells. We observed saturable ATP-dependent
      transport into membrane vesicles expressing human MRP2. We also found that the
      elimination of intravenously administered valsartan from plasma was markedly
      delayed, and the biliary excretion was severely impaired in EHBR compared with
      normal Sprague-Dawley rats. These results suggest that OATP1B1 and OATP1B3 as the
      uptake transporters and MRP2 as the efflux transporter are responsible for the
      efficient hepatobiliary transport of valsartan.

PMID- 16624872
TI  - Guidelines for the prevention of endocarditis: report of the Working Party of the
      British Society for Antimicrobial Chemotherapy.
AB  - These guidelines have been produced following a literature review of the
      requirement for prophylaxis to prevent bacterial endocarditis following dental
      and surgical interventions. Recommendations are made based on the quality of
      available evidence and the consequent risk of morbidity and mortality for "at
      risk" patients.

PMID- 16624873
TI  - Another set of endocarditis guidelines?

PMID- 16624874
TI  - Selection of ciprofloxacin resistance in Escherichia coli in an in vitro kinetic
      model: relation between drug exposure and mutant prevention concentration.
AB  - OBJECTIVES: To evaluate the mutant prevention concentrations (MPCs) of
      ciprofloxacin for two susceptible and one first-step gyrA resistant mutant
      Escherichia coli strains in an in vitro kinetic model and to identify the
      pharmacodynamic index that best predicts prevention of resistance emergence.
      METHODS: An in vitro kinetic model was used to measure MPC with static antibiotic
      concentrations and to test different dosing profiles to study
      pharmacokinetics/pharmacodynamics indices important to prevent the growth of
      resistant mutants. In one set of kinetic experiments the starting concentration
      was equal to the MPC and the T > MPC was varied before antibiotic dilution was
      begun. In a second set of kinetic experiments C(max) was varied and dilution of
      the antibiotic was started at time zero. RESULTS: From the static experiments we
      calculated MPC values of 0.128 mg/L for both the susceptible strains (16x MIC)
      and 0.188 mg/L (4x MIC) for the first-step resistant (gyrA) strain. The kinetic
      experiments showed that the T > MPC needed to prevent the growth of resistant
      bacteria was shorter with an increased C(max). When resistance was selected,
      several subpopulations with different levels of susceptibility to ciprofloxacin
      emerged. CONCLUSIONS: Neither T > MPC nor C(max) proved to be single correlates
      for preventing resistance development. For the two investigated wild-type
      strains, an AUC/MPC ratio of > or =22 was the single pharmacodynamic index that
      predicted prevention of resistant mutant development.

PMID- 16624875
TI  - Antimicrobial resistance: paradox, actions and economics.
AB  - The threat from antimicrobial-resistant organisms is accumulating and
      accelerating. One strand of the action that an adequate response to this threat
      demands is good clinical governance through management and audit of antimicrobial
      prescribing in hospitals. This is the subject of another article in this issue of
      the Journal, which describes the guidelines developed by the Scottish Medicines
      Consortium and Scottish Health Executive to tackle this problem. However, the
      problems posed by resistant organisms are wider still. In a period of increased
      threat, innovation (new drugs and technologies) seems to be in decline. There are
      grounds for serious concern that the current economic model is not capable of
      responding adequately. Governments need to acknowledge and address this fact.
      Patient outcomes will suffer increasingly if governments do not act to change the
      status quo.

PMID- 16624876
TI  - Antimicrobial prescribing policy and practice in Scotland: recommendations for
      good antimicrobial practice in acute hospitals.
AB  - This guidance document on prudent use of antibiotics and other antimicrobial
      drugs has been produced for NHSScotland by the Scottish Medicines Consortium
      (SMC). It fulfils one of the requirements set out in the Antimicrobial Resistance
      Strategy and Scottish Action Plan (Scottish Executive Health Department 2002) and
      forms part of the Healthcare Associated Infection (HAI) Action Plan work
      programme overseen by the Ministerial HAI Task Force. The objective was the
      development of a set of Good Practice Recommendations for Antimicrobial
      Prescribing in Hospitals to be implemented at the national or local level. The
      publication of the recommendations of this document in the Journal of
      Antimicrobial Chemotherapy (JAC) aims to highlight the value of such a national
      framework to a broader national and international community, particularly aimed
      at those decision-makers involved in antimicrobial stewardship. While some of its
      content may only be applicable to a devolved Scottish Health Care system we feel
      that many of the principles and good practice points are of generic concern and
      would be of relevance and value to all acute hospitals. On behalf of the all the
      authors involved in producing this document it is our hope that this article will
      stimulate debate and action within our acute hospitals.

PMID- 16624877
TI  - Differential induction of BLT receptor expression on human endothelial cells by
      lipopolysaccharide, cytokines, and leukotriene B4.
AB  - Leukotriene (LT) B4 is a powerful chemotactic and immune modulating agent that
      signals via two receptors denoted BLT1 and BLT2. Here we report that BLT1 and
      BLT2 are expressed at low levels in an apparently silent state in human umbilical
      vein endothelial cells (HUVEC). However, treatment with LPS leads to a >10 fold
      increase in the levels of BLT1 mRNA without any significant effects on BLT2 mRNA.
      In parallel, LPS also increases the amounts of BLT1 protein. Tumor necrosis
      factor-alpha (TNF-alpha) increases the expression of BLT2 mRNA approximately 6
      times above basal levels with only a modest increase in BLT1 mRNA. Interleukin
      1beta causes variable and parallel increases of both BLT1 and BLT2 mRNA. The
      natural ligand LTB4 also increases BLT1, but not BLT2, mRNA and protein
      expression. Along with the induction of BLT1 and/or BLT2, HUVEC acquire the
      capacity to respond to LTB4 with increased levels of intracellular calcium and
      these signals can be blocked by isotype selective BLT antagonists, CP-105696 and
      LY-255283. In addition, treatment of HUVEC with LTB4 causes increased release of
      both nitrite, presumably reflecting nitric oxide (NO), and monocyte
      chemoattractant protein-1. Our data indicate that expression of functional BLT
      receptors may occur at the surface of endothelial cells in response to LPS,
      cytokines, and ligand, which in turn may have functional consequences during the
      early vascular responses to inflammation. Moreover, the results point to BLT
      receptors as potential targets for pharmacological intervention in LT-dependent
      inflammatory diseases such as asthma, rheumatoid arthritis, and arteriosclerosis.

PMID- 16624878
TI  - Site-specific proteolysis of the transcriptional coactivator HCF-1 can regulate
      its interaction with protein cofactors.
AB  - Limited proteolytic processing is an important transcriptional regulatory
      mechanism. In various contexts, proteolysis controls the cytoplasmic-to-nuclear
      transport of important transcription factors or removes domains to produce
      factors with altered activities. The transcriptional coactivator host cell factor
      1 (HCF-1) is proteolytically processed within a unique domain consisting of 20-aa
      reiterations. Site-specific cleavage within one or more repeats generates a
      family of amino- and carboxyl-terminal subunits that remain tightly associated.
      However, the consequences of HCF-1 processing have been undefined. In this study,
      it was determined that the HCF-1-processing domain interacts with several
      proteins including the transcriptional coactivator/corepressor four-and-a-half
      LIM domain-2 (FHL2). Analysis of this interaction has uncovered specificity with
      both sequence and context determinants within the reiterations of this processing
      domain. In cells, FHL2 interacts exclusively with the nonprocessed coactivator
      and costimulates transcription of an HCF-1-dependent target gene. The functional
      interaction of HCF-1 with FHL2 supports a model in which site-specific
      proteolysis regulates the interaction of HCF-1 with protein partners and thus can
      modulate the activity of this coactivator. This paradigm expands the biological
      significance of limited proteolytic processing as a regulatory mechanism in gene
      transcription.

PMID- 16624879
TI  - Common attributes of native-state structures of proteins, disordered proteins,
      and amyloid.
AB  - We show that a framework derived from the common character of globular proteins
      can be used to understand the design of protein sequences, the behavior of
      intrinsically unstructured proteins, and the formation of amyloid fibrils in a
      unified manner. Our studies provide compelling support for the idea that protein
      native-state structures, the structures adopted by intrinsically unstructured
      proteins on binding as well as those of amyloid aggregates, all reside in a
      physical state of matter in which the free energy landscape is sculpted not by
      the specific sequence of amino acids, but rather by considerations of geometry
      and symmetry. We elucidate the key role played by sequence design in selecting
      the structure of choice from the predetermined menu of putative native-state
      structures.

PMID- 16624881
TI  - Chorioamnionitis with or without funisitis increases the risk of hypotension in
      very low birthweight infants on the first postnatal day but not later.
AB  - OBJECTIVE: To evaluate the relation between chorioamnionitis and hypotension in
      very low birthweight infants. METHODS: Retrospective cohort study in infants with
      a birth weight of <1500 g born between January 2002 and September 2004. The
      placentas were examined for evidence of chorioamnionitis and funisitis.
      Hypotension was defined by the use of vasopressors. RESULTS: Of 105 infants, 37
      (35%) were chorioamnionitis positive. The onset of hypotension had a skewed
      distribution: day 1 for 30 episodes and scattered from day 2 to day 19 for the
      remaining 22. Of the 30 infants who developed hypotension on day 1, 17 (57%) were
      chorioamnionitis positive. The mean maturity of the chorioamnionitis positive
      group was 27.91 weeks, marginally less than the mean maturity of 29.05 weeks of
      the chorioamnionitis negative group (p = 0.05). After adjustment of the effects
      for confounding variables (birth weight, gestation, surfactant therapy,
      mechanical ventilation on day 1, high frequency oscillatory ventilation, patent
      ductus arteriosus), chorioamnionitis was the significant factor in line with
      hypotension developing on day 1 (adjusted odds ratio 5.14, 95% confidence
      interval 1.51 to 17.50). There was no evidence that hypotension developing after
      day 1 was associated with chorioamnionitis. CONCLUSIONS: There is a strong
      association between chorioamnionitis and hypotension developing on day 1 in very
      low birthweight infants.

PMID- 16624882
TI  - Prednisolone versus dexamethasone in croup: a randomised equivalence trial.
AB  - BACKGROUND: Croup remains a common respiratory problem presenting to emergency
      departments. A single oral treatment of oral dexamethasone results in improved
      outcome. Prednisolone has similar pharmacokinetic properties and has a
      significant advantage in that it is commercially available in liquid
      preparations. OBJECTIVE: To ascertain whether a single oral dose of prednisolone
      was equivalent to a single oral dose of dexamethasone (matched for potency) in
      children with mild to moderate croup. DESIGN: A double blind, randomised,
      controlled equivalence trial. SETTING: Tertiary paediatric emergency department.
      PATIENTS: 133 children aged 3 to 142 months presenting with mild to moderate
      croup. INTERVENTIONS: Children received either a single oral dose of
      dexamethasone 0.15 mg/kg or single oral dose of prednisolone 1 mg/kg. OUTCOME:
      The main outcome measure was unscheduled re-presentation to medical care as
      determined by telephone follow up at 7 to 10 days. Croup score, adrenaline
      (epinephrine) use, time spent in the emergency department, and duration of croup
      and viral symptoms were secondary outcome measures. RESULTS: Children treated
      with prednisolone were more likely to re-present: 19 of 65 children (29%)
      reattended medical care compared with 5 of 68 (7%) from the dexamethasone group.
      The confidence intervals around this 22% difference in outcome were 8% to 35%,
      outside the 0% to 7.5% range of equivalence. There were no significant
      differences in other outcome measures. CONCLUSION: A single oral dose of
      prednisolone is less effective than a single oral dose of dexamethasone in
      reducing unscheduled re-presentation to medical care in children with mild to
      moderate croup.

PMID- 16624880
TI  - DEMETER and REPRESSOR OF SILENCING 1 encode 5-methylcytosine DNA glycosylases.
AB  - Cytosine methylation is an epigenetic mark that promotes gene silencing and plays
      important roles in development and genome defense against transposons.
      Methylation patterns are established and maintained by DNA methyltransferases
      that catalyze transfer of a methyl group from S-adenosyl-L-methionine to cytosine
      bases in DNA. Erasure of cytosine methylation occurs during development, but the
      enzymatic basis of active demethylation remains controversial. In Arabidopsis
      thaliana, DEMETER (DME) activates the maternal expression of two imprinted genes
      silenced by methylation, and REPRESSOR OF SILENCING 1 (ROS1) is required for
      release of transcriptional silencing of a hypermethylated transgene. DME and ROS1
      encode two closely related DNA glycosylase domain proteins, but it is unknown
      whether they participate directly in a DNA demethylation process or counteract
      silencing through an indirect effect on chromatin structure. Here we show that
      DME and ROS1 catalyze the release of 5-methylcytosine (5-meC) from DNA by a
      glycosylase/lyase mechanism. Both enzymes also remove thymine, but not uracil,
      mismatched to guanine. DME and ROS1 show a preference for 5-meC over thymine in
      the symmetric dinucleotide CpG context, where most plant DNA methylation occurs.
      Nevertheless, they also have significant activity on both substrates at CpApG and
      asymmetric sequences, which are additional methylation targets in plant genomes.
      These findings suggest that a function of ROS1 and DME is to initiate erasure of
      5-meC through a base excision repair process and provide strong biochemical
      evidence for the existence of an active DNA demethylation pathway in plants.

PMID- 16624883
TI  - Meconium and neurotoxicants: searching for a prenatal exposure timing.
AB  - BACKGROUND: Exposure to organochlorine compounds (OCs) has been a subject of
      interest in recent years, given their potential neurotoxicity. Meconium is easily
      available and accumulates neurotoxicants and/or metabolites from the 12th week of
      gestation. AIMS: To determine whether neurotoxicants, specifically OCs, could be
      detected in serially collected meconium, and to compare the results with those
      obtained in cord blood samples. METHODS: A sample of cord blood and three serial
      stool samples were analysed in 10 newborns. Pentachlorobenzene (PeCB),
      hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), dichlorodiphenyl
      trichloroethane (p,p'-DDT) and its metabolite dichlorodiphenyl dichloroethylene
      (p,p'-DDE), and hexachlorocyclohexane isomers (alpha-, beta-, gamma-, and delta
      HCH) were analysed by gas chromatography. RESULTS: From serial stool collection
      and analysis in newborns, there was an increase in the concentrations of HCB,
      p,p'-DDE, PCBs, and beta-HCH between the first and last stools of the newborn.
      Levels of DDT diminished as pregnancy progressed. Concentrations in cord blood
      were positively associated with concentrations in meconium for p,p'-DDE and beta
      HCH. CONCLUSIONS: Meconium is a very useful instrument for the investigation of
      fetal exposure to neurotoxicants; serial collection and analysis of meconium
      should estimate the timing and degree of in utero exposure of the fetus to
      neurotoxicants. Analysis and interpretation of neurotoxicants in meconium results
      is a complex process. Measurement in meconium of a wide range of neurotoxic
      substances should facilitate early identification of harmful exposures, and
      enable rehabilitation and instigation of preventive measures.

PMID- 16624885
TI  - Correlation between anemia and functional/cognitive capacity in elderly lung
      cancer patients treated with chemotherapy.

PMID- 16624884
TI  - Consensus statement on management of intersex disorders.

PMID- 16624886
TI  - Specific rescue of cystic fibrosis transmembrane conductance regulator processing
      mutants using pharmacological chaperones.
AB  - Most mutants of the cystic fibrosis transmembrane conductance regulator (CFTR)
      that cause severe symptoms of cystic fibrosis do not reach the cell surface
      because they are defective in folding. Many CFTR folding mutants, however,
      including the DeltaF508 mutant found in more than 90% of cystic fibrosis
      patients, are potentially functional at the cell surface if they can be induced
      to fold correctly. In a previous study (Mol Pharm 2:407-413, 2005), we reported
      that a quinazoline derivative (CFcor-325) could rescue CFTR processing mutants.
      The corrector was not specific however, as it could also rescue a processing
      mutant of CFTR's sister protein, the multidrug resistance P-glycoprotein. The
      goal of this study was to test whether it was possible to specifically rescue
      CFTR processing mutants using a pharmacological chaperone. In this article, we
      report that two compounds, 4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)-phenol (CFpot
      532) and 2-phenylamino-4-(4-ethylene-phenyl)-thiazole (corr-2b) could rescue CFTR
      processing mutants such as DeltaF508 CFTR but not a P-glycoprotein processing
      mutant. The compound CFpot-532 also acts as a potentiator of DeltaF508 CFTR
      channel activity. Therefore, the results suggest that the mechanism whereby CFpot
      532 and corr-2b promote folding of CFTR processing mutants is through direct
      interaction with the CFTR mutant proteins. The compound CFpot-532 could be a
      particularly useful lead compound for treatment of cystic fibrosis because it is
      both a CFTR channel potentiator as well as a specific pharmacological chaperone.

PMID- 16624887
TI  - The potential for developing a routine screening and assessment program to
      evaluate emotional distress in children with cancer.

PMID- 16624888
TI  - The importance of being there: perspectives of social support by adolescents with
      cancer.
AB  - Adolescents with cancer are confronted with many challenges. The extent to which
      they are able to deal with such challenges appears to be partly contingent on a
      positive strong social support system. In this article, the author describes
      findings specific to the sources of social support that 15 adolescents with
      cancer found to be most important in getting them through the cancer experience.
      Data were collected as part of a longitudinal qualitative interpretive study and
      involved individual interviews, focus group interviews, and participant
      observation as the main sources of data. The relationships that adolescents
      maintained with their nuclear families, health care team members, and special
      friends were the 3 main supportive relationships in the adolescents'lives. The
      act of others "being there" was seen by the adolescents as the key element of a
      supportive relationship and involved 6 main behaviors. Although the 3 key
      supportive relationships were essential in helping adolescents get through
      cancer, these relationships were at times a source of stress for adolescents.

PMID- 16624889
TI  - An examination of physical activity behaviors in a sample of adolescent cancer
      survivors.
AB  - With a growing consensus of the importance of physical activity across a number
      of health outcomes, the current study investigated the impact of a cancer
      diagnosis on adolescent physical activity behavior. Participants (n=97) completed
      a mailed, self-administered questionnaire in which they recalled their physical
      activity behaviors across the cancer experience. Examination of the data revealed
      that adolescents treated for cancer experience significant declines in physical
      activity that are not recovered following treatment completion. It is not clear
      if the sustained reduction in posttreatment physical activity is attributable to
      the lingering effects of cancer treatment, but the long-term implications of a
      reduction in physical activity may be far-reaching.

PMID- 16624890
TI  - The lived experience of adult survivors of childhood cancer.
AB  - Little is known about the long-term impact of surviving childhood cancer. Most
      children diagnosed with cancer now survive into adulthood due to advances in
      medical treatment. Although the number of survivors of childhood cancer has
      increased, a review of the literature revealed a paucity of studies that explores
      survivorship of childhood cancer from the perspective of the adult survivor. The
      purpose of this phenomenological study was to examine the lived experience of 12
      adults who survived childhood cancer. This research methodology allows the
      meaning or essences of experiences that occurred to be uncovered. Four themes
      emerged from these data: (1) ongoing consequences for having had cancer, (2)
      living with uncertainty, (3) the cancer experience is embodied into one's present
      sense of self, and (4) support is valued. The results of this study demonstrate
      that a childhood cancer experience affects the life of each survivor, which
      results in specific health care needs. This knowledge is important as the number
      of survivors increases. Knowledge of their concerns is imperative prior to
      providing appropriate health care.

PMID- 16624891
TI  - Personal Web home pages of adolescents with cancer: self-presentation,
      information dissemination, and interpersonal connection.
AB  - The content of personal Web home pages created by adolescents with cancer is a
      new source of information about this population of potential benefit to oncology
      nurses and psychologists. Individual Internet elements found on 21 home pages
      created by youths with cancer (14-22 years old) were rated for cancer-related
      self-presentation, information dissemination, and interpersonal connection.
      Examples of adolescents' online narratives were also recorded. Adolescents with
      cancer used various Internet elements on their home pages for cancer-related self
      presentation (eg, welcome messages, essays, personal history and diary pages,
      news articles, and poetry), information dissemination (e.g., through personal
      interest pages, multimedia presentations, lists, charts, and hyperlinks), and
      interpersonal connection (eg, guestbook entries). Results suggest that various
      elements found on personal home pages are being used by a limited number of young
      patients with cancer for self-expression, information access, and contact with
      peers.

PMID- 16624893
TI  - SNP identification and analysis in part of intron 2 of goat MSTN gene and
      variation within and among species.
AB  - Part of intron 2 of the myostatin (MSTN) gene of 140 goats from 24 populations
      and 38 sheep from 8 breeds were sequenced, and similar sequences of different
      species from Gene bank were also obtained to study MSTN diversity within and
      among species. The results indicated that there were seven polymorphic sites in
      the sequenced region of goat, which have not been separated by recombination (or
      recurrent mutation), presented complete linkage disequilibrium, and could be
      sorted into three haplotypes. There was no polymorphic site in the sequenced
      region of sheep. The haplotype diversity, nucleotide diversity, and average
      number of single nucleotide polymorphism (SNP) differences of goats from the
      South group are higher than those of North group, and the corresponding value of
      the Foreign group is also higher than that of Chinese. The genetic
      differentiation (0.7558) between the Foreign and Chinese group is significant.
      There are two main haplotypes of the MSTN intron 2 in the goat, which may
      represent two ancestral types, in support of the theory that domestic goats in
      the world mainly originated from two ancestors based on morphology, history,
      archaeology, and molecular markers. The sequence differences of the MSTN intron 2
      among species are greater than those within species.

PMID- 16624894
TI  - N-Acetylgalactosamine 4,6-O-sulfate residues mediate binding and activation of
      heparin cofactor II by porcine mucosal dermatan sulfate.
AB  - Dermatan sulfate (DS) accelerates the inhibition of thrombin by heparin cofactor
      II (HCII). A hexasaccharide consisting of three l-iduronic acid 2-O-sulfate
      (IdoA2SO3)-->N-acetyl-D-galactosamine 4-O-sulfate (GalNAc4SO3) subunits was
      previously isolated from porcine skin DS and shown to bind HCII with high
      affinity. DS from porcine intestinal mucosa has a much lower content of this
      disaccharide but activates HCII with potency similar to that of porcine skin DS.
      Therefore, we sought to characterize oligosaccharides from porcine mucosal DS
      that interact with HCII. DS was partially depolymerized with chondroitinase ABC,
      and oligosaccharides containing 2-12 monosaccharide units were isolated. The
      oligosaccharides were then fractionated by anion-exchange and affinity
      chromatography on HCII-Sepharose, and the disaccharide compositions of selected
      fractions were determined. We found that the smallest oligosaccharides able to
      bind HCII were hexasaccharides. Oligosaccharides 6-12 units long that lacked
      uronic acid (UA)2SO3 but contained one or two GalNAc4,6SO3 residues bound, and
      binding was proportional to both oligosaccharide size and number of GalNAc4,6SO3
      residues. Intact DS and bound dodecasaccharides contained predominantly IdoA but
      little D-glucuronic acid. Decasaccharides and dodecasaccharides containing one or
      two GalNAc4,6SO3 residues stimulated thrombin inhibition by HCII and prolonged
      the clotting time of normal but not HCII-depleted human plasma. These data
      support the hypothesis that modification of IdoA-->GalNAc4SO3 subunits in the DS
      polymer by either 2-O-sulfation of IdoA or 6-O-sulfation of GalNAc can generate
      molecules with HCII-binding sites and anticoagulant activity.

PMID- 16624895
TI  - N-Acetylglucosamine 6-O-sulfotransferase-1 is required for brain keratan sulfate
      biosynthesis and glial scar formation after brain injury.
AB  - Keratan sulfate (KS) is a glycosaminoglycan composed of repeating disaccharide
      units with sulfate residues at the C6 positions of galactose and N
      acetylglucosamine (GlcNAc). The N-acetylglucosamine 6-O-sulfotransferase(s)
      (GlcNAc6ST) involved in the synthesis of KS in the central nervous system (CNS)
      has long been unidentified. Here, we report that a deficiency of GlcNAc6ST-1
      leads to loss of 5D4-reactive brain KS and reduction of glial scar formation
      after cortical stab injury in mice. During the development of mice deficient in
      GlcNAc6ST-1, KS expression in the brain was barely detectable with the KS
      specific antibody 5D4. The reactivity of 5D4 antibody with protein tyrosine
      phosphatase zeta (PTPzeta), a KS proteoglycan (KSPG), was abolished in the
      deficient mice. In adults, brain injury induced 5D4-reactive KS synthesis in the
      wounded area in wild-type (WT) mice but not in the deficient mice. Glial scar is
      formed via the accumulation of reactive astrocytes and is a major obstacle to
      axonal regeneration by injured neurons. Reactive astrocytes appeared to similar
      extents in the two genotypes, but they accumulated in the wounded area to a
      lesser extent in the deficient mice. Consequently, the deficient mice exhibited a
      marked reduction of scarring and enhanced neuronal regeneration after brain
      injury. These findings highlight the indispensable role of GlcNAc6ST-1 in brain
      KS biosynthesis and glial scar formation after brain injury.

PMID- 16624896
TI  - Numerous and rapid nonstochastic modifications of gene products in newly
      synthesized Brassica napus allotetraploids.
AB  - Polyploidization is a widespread process that results in the merger of two or
      more genomes in a common nucleus. To investigate modifications of gene expression
      occurring during allopolyploid formation, the Brassica napus allotetraploid model
      was chosen. Large-scale analyses of the proteome were conducted on two organs,
      the stem and root, so that >1600 polypeptides were screened. Comparative
      proteomics of synthetic B. napus and its homozygous diploid progenitors B. rapa
      and B. oleracea showed that very few proteins disappeared or appeared in the
      amphiploids (<1%), but a strikingly high number (25-38%) of polypeptides
      displayed quantitative nonadditive pattern. Nonstochastic gene expression
      repatterning was found since 99% of the detected variations were reproducible in
      four independently created amphiploids. More than 60% of proteins displayed a
      nonadditive pattern closer to the paternal parent B. rapa. Interspecific
      hybridization triggered the majority of the deviations (89%), whereas very few
      variations (approximately 3%) were associated with genome doubling and more
      significant alterations arose from selfing (approximately 9%). Some nonadditive
      proteins behaved similarly in both organs, while others exhibited contrasted
      behavior, showing rapid organ-specific regulation. B. napus formation was
      therefore correlated with immediate and directed nonadditive changes in gene
      expression, suggesting that the early steps of allopolyploidization repatterning
      are controlled by nonstochastic mechanisms.

PMID- 16624897
TI  - Complex inheritance of the 5-lipoxygenase locus influencing atherosclerosis in
      mice.
AB  - We previously mapped a locus on chromosome 6 with a large effect (LOD > 6) on
      aortic lesion size in a (C57BL/6J x CAST/Ei) F(2) cross and identified
      arachidonate 5-lipoxygenase (5LO) as a candidate gene in this region. Subsequent
      studies with the 5LO knockout model showed effects on atherosclerosis and aortic
      aneurysms. We now report detailed genetic analysis of the chromosome 6 locus. We
      created a panel of overlapping and reciprocal subcongenic lines from the B6.CAST
      Ldlr(-/-) chromosome 6 congenic strain (CON6.Ldlr(-/-)) and analyzed aortic
      lesion size in different subcongenic lines. Our results revealed that there are
      at least two subregions, designated as Ath37 and Ath38 that affect the size of
      aortic lesions independently of 5LO. We also showed that homozygote 5LO null mice
      develop smaller atherosclerotic lesions. We conclude that the relation between
      the mouse chromosome 6 locus and atherosclerosis is complex and is due to at
      least two genes with large effects within this region. This complexity should be
      considered when interpreting results of knockout studies.

PMID- 16624898
TI  - Definition of a 1.06-Mb region linked to neuroinflammation in humans, rats and
      mice.
AB  - Unbiased identification of susceptibility genes might provide new insights into
      pathogenic mechanisms that govern complex inflammatory diseases such as multiple
      sclerosis. In this study we fine mapped Eae18a, a region on rat chromosome 10
      that regulates experimental autoimmune encephalomyelitis (EAE), an animal model
      for multiple sclerosis. We utilized two independent approaches: (1) in silico
      mapping based on sequence similarity between human multiple sclerosis
      susceptibility regions and rodent EAE quantitative trait loci and (2) linkage
      mapping in an F10 (DA x PVG.AV1) rat advanced intercrossed line. The linkage
      mapping defines Eae18a to a 5-Mb region, which overlaps one intergenomic
      consensus region identified in silico. The combined approach confirms
      experimentally, for the first time, the accuracy of the in silico method.
      Moreover, the shared intersection between the results of both mapping techniques
      defines a 1.06-Mb region containing 13 candidate genes for the regulation of
      neuroinflammation in humans, rats, and mice.

PMID- 16624899
TI  - Mapping novel traits by array-assisted bulk segregant analysis in Saccharomyces
      cerevisiae.
AB  - We demonstrate a new method, microarray-assisted bulk segregant analysis, for
      mapping traits in yeast by genotyping pooled segregants. We apply a probabilistic
      model to the progeny of a single cross and as little as two microarray
      hybridizations to reliably map an auxotrophic marker, a Mendelian trait, and a
      major-effect quantitative trait locus.

PMID- 16624900
TI  - Genes that control ray sensory neuron axon development in the Caenorhabditis
      elegans male.
AB  - We have studied how a set of male-specific sensory neurons in Caenorhabditis
      elegans establish axonal connections during postembryonic development. In the
      adult male, 9 bilateral pairs of ray sensory neurons innervate an acellular fan
      that serves as a presumptive tactile and olfactory organ during copulation. We
      visualized ray axon commissures with a ray neuron-specific reporter gene and
      studied both known and new mutations that affect the establishment of connections
      to the pre-anal ganglion. We found that the UNC-6/netrin-UNC-40/DCC pathway
      provides the primary dorsoventral guidance cue to ray axon growth cones. Some
      axon growth cones also respond to an anteroposterior cue, following a segmented
      pathway, and most or all also have a tendency to fasciculate. Two newly
      identified genes, rax-1 and rax-4, are highly specific to the ray neurons and
      appear to be required for ray axon growth cones to respond to the dorsoventral
      cue. Among other genes we identified, rax-2 and rax-3 affect anteroposterior
      signaling or fate specification and rax-5 and rax-6 affect ray identities. We
      identified a mutation in sax-2 and show that the sax-2/Furry and sax
      1/Tricornered pathway affects ectopic neurite outgrowth and establishment of
      normal axon synapses. Finally, we identified mutations in genes for muscle
      proteins that affect axon pathways by distorting the conformation of the body
      wall. Thus ray axon pathfinding relies on a variety of general and more ray
      neuron-specific genes and provides a potentially fruitful system for further
      studies of how migrating axon growth cones locate their targets. This system is
      applicable to the study of mechanisms underlying topographic mapping of sensory
      neurons into target circuitry where the next stage of information processing is
      carried out.

PMID- 16624901
TI  - A defect in protein farnesylation suppresses a loss of Schizosaccharomyces pombe
      tsc2+, a homolog of the human gene predisposing to tuberous sclerosis complex.
AB  - Mutations in the human Tsc1 and Tsc2 genes predispose to tuberous sclerosis
      complex (TSC), a disorder characterized by the wide spread of benign tumors. Tsc1
      and Tsc2 proteins form a complex and serve as a GTPase-activating protein (GAP)
      for Rheb, a GTPase regulating a downstream kinase, mTOR. The genome of
      Schizosaccharomyces pombe contains tsc1(+) and tsc2(+), homologs of human Tsc1
      and Tsc2, respectively. In this study we analyzed the gene expression profile on
      a genomewide scale and found that deletion of either tsc1(+) or tsc2(+) affects
      gene induction upon nitrogen starvation. Three hours after nitrogen depletion
      genes encoding permeases and genes required for meiosis are less induced. Under
      the same condition, retrotransposons, G1-cyclin (pas1(+)), and inv1(+) are more
      induced. We also demonstrate that a mutation (cpp1-1) in a gene encoding a beta
      subunit of a farnesyltransferase can suppress most of the phenotypes associated
      with deletion of tsc1(+) or tsc2(+). When a mutant of rhb1(+) (homolog of human
      Rheb), which bypasses the requirement of protein farnesylation, was expressed,
      the cpp1-1 mutation could no longer suppress, indicating that deficient
      farnesylation of Rhb1 contributes to the suppression. On the basis of these
      results, we discuss TSC pathology and possible improvement in chemotherapy for
      TSC.

PMID- 16624902
TI  - Partitioning of the maize epigenome by the number of methyl groups on histone H3
      lysines 9 and 27.
AB  - We report a detailed analysis of maize chromosome structure with respect to seven
      histone H3 methylation states (dimethylation at lysine 4 and mono-, di-, and
      trimethylation at lysines 9 and 27). Three-dimensional light microscopy and the
      fine cytological resolution of maize pachytene chromosomes made it possible to
      compare the distribution of individual histone methylation events to each other
      and to DNA staining intensity. Major conclusions are that (1) H3K27me2 marks
      classical heterochromatin; (2) H3K4me2 is limited to areas between and around
      H3K27me2-marked chromomeres, clearly demarcating the euchromatic gene space; (3)
      H3K9me2 is restricted to the euchromatic gene space; (4) H3K27me3 occurs in a few
      (roughly seven) focused euchromatic domains; (5) centromeres and CENP-C are
      closely associated with H3K9me2 and H3K9me3; and (6) histone H4K20 di- and
      trimethylation are nearly or completely absent in maize. Each methylation state
      identifies different regions of the epigenome. We discuss the evolutionary
      lability of histone methylation profiles and draw a distinction between H3K9me2
      mediated gene silencing and heterochromatin formation.

PMID- 16624903
TI  - High-resolution radiation hybrid map of wheat chromosome 1D.
AB  - Physical mapping methods that do not rely on meiotic recombination are necessary
      for complex polyploid genomes such as wheat (Triticum aestivum L.). This need is
      due to the uneven distribution of recombination and significant variation in
      genetic to physical distance ratios. One method that has proven valuable in a
      number of nonplant and plant systems is radiation hybrid (RH) mapping. This work
      presents, for the first time, a high-resolution radiation hybrid map of wheat
      chromosome 1D (D genome) in a tetraploid durum wheat (T. turgidum L., AB genomes)
      background. An RH panel of 87 lines was used to map 378 molecular markers, which
      detected 2312 chromosome breaks. The total map distance ranged from approximately
      3,341 cR(35,000) for five major linkage groups to 11,773 cR(35,000) for a
      comprehensive map. The mapping resolution was estimated to be approximately 199
      kb/break and provided the starting point for BAC contig alignment. To date, this
      is the highest resolution that has been obtained by plant RH mapping and serves
      as a first step for the development of RH resources in wheat.

PMID- 16624904
TI  - Identification and classification of genes that act antagonistically to let-60
      Ras signaling in Caenorhabditis elegans vulval development.
AB  - The synthetic multivulva (synMuv) genes negatively regulate Ras-mediated vulval
      induction in the nematode Caenorhabditis elegans. The synMuv genes define three
      classes, A, B, and C, such that double mutants carrying mutations in genes of any
      two classes are multivulva. The class B synMuv genes include lin-35, a homolog of
      the retinoblastoma (Rb) tumor suppressor gene, as well as homologs of genes that
      function with Rb in transcriptional regulation. We screened for additional synMuv
      mutations using a strategy different from that of previous synMuv genetic
      screens. Some of the mutations we recovered affect new synMuv genes. We present
      criteria for assigning synMuv mutations into different genetic classes. We also
      describe the molecular characterization of the class B synMuv gene lin-65.

PMID- 16624905
TI  - Modified Hudson-Kreitman-Aguade test and two-dimensional evaluation of neutrality
      tests.
AB  - There are a number of polymorphism-based statistical tests of neutrality, but
      most of them focus on either the amount or the pattern of polymorphism. In this
      article, a new test called the two-dimensional (2D) test is developed. This test
      evaluates a pair of summary statistics in a two-dimensional field. One statistic
      should summarize the pattern of polymorphism, while the other could be a measure
      of the level of polymorphism. For the latter summary statistic, the polymorphism
      divergence ratio is used following the idea of the Hudson-Kreitman-Aguade (HKA)
      test. To incorporate the HKA test in the 2D test, a summary statistic-based
      version of the HKA test is developed such that the polymorphism-divergence ratio
      at a particular region of interest is examined if it is consistent with the
      average of those in other independent regions.

PMID- 16624906
TI  - A simple linear regression method for quantitative trait loci linkage analysis
      with censored observations.
AB  - Standard quantitative trait loci (QTL) mapping techniques commonly assume that
      the trait is both fully observed and normally distributed. When considering
      survival or age-at-onset traits these assumptions are often incorrect. Methods
      have been developed to map QTL for survival traits; however, they are both
      computationally intensive and not available in standard genome analysis software
      packages. We propose a grouped linear regression method for the analysis of
      continuous survival data. Using simulation we compare this method to both the Cox
      and Weibull proportional hazards models and a standard linear regression method
      that ignores censoring. The grouped linear regression method is of equivalent
      power to both the Cox and Weibull proportional hazards methods and is
      significantly better than the standard linear regression method when censored
      observations are present. The method is also robust to the proportion of censored
      individuals and the underlying distribution of the trait. On the basis of linear
      regression methodology, the grouped linear regression model is computationally
      simple and fast and can be implemented readily in freely available statistical
      software.

PMID- 16624907
TI  - Adaptive divergence in experimental populations of Pseudomonas fluorescens. II.
      Role of the GGDEF regulator WspR in evolution and development of the wrinkly
      spreader phenotype.
AB  - Wrinkly spreader (WS) genotypes evolve repeatedly in model Pseudomonas
      populations undergoing adaptive radiation. Previous work identified genes
      contributing to the evolutionary success of WS. Here we scrutinize the GGDEF
      response regulator protein WspR and show that it is both necessary and sufficient
      for WS. Activation of WspR occurs by phosphorylation and different levels of
      activation generate phenotypic differences among WS genotypes. Five alleles of
      wspR, each encoding a protein with a single amino acid substitution, were
      generated by mutagenesis. Two alleles are constitutively active and cause the
      ancestral genotype to develop a WS phenotype; the phenotypic effects are allele
      specific and independent of phosphorylation. Three alleles contain changes in the
      GGDEF domain and when overexpressed in WS cause reversion to the ancestral
      phenotype. Ability to mimic this effect by overexpression of a liberated N
      terminal domain shows that in WS, regulatory components upstream of WspR are
      overactive. To connect changes at the nucleotide level with fitness, the effects
      of variant alleles were examined in both structured and unstructured
      environments: alleles had adaptive and deleterious effects with trade-offs
      evident across environments. Despite the proclivity of mutations within wspR to
      generate WS, sequence analysis of wspR from 53 independently obtained WS showed
      no evidence of sequence change in this gene.

PMID- 16624908
TI  - Using approximate Bayesian computation to estimate tuberculosis transmission
      parameters from genotype data.
AB  - Tuberculosis can be studied at the population level by genotyping strains of
      Mycobacterium tuberculosis isolated from patients. We use an approximate Bayesian
      computational method in combination with a stochastic model of tuberculosis
      transmission and mutation of a molecular marker to estimate the net transmission
      rate, the doubling time, and the reproductive value of the pathogen. This method
      is applied to a published data set from San Francisco of tuberculosis genotypes
      based on the marker IS6110. The mutation rate of this marker has previously been
      studied, and we use those estimates to form a prior distribution of mutation
      rates in the inference procedure. The posterior point estimates of the key
      parameters of interest for these data are as follows: net transmission rate,
      0.69/year [95% credibility interval (C.I.) 0.38, 1.08]; doubling time, 1.08 years
      (95% C.I. 0.64, 1.82); and reproductive value 3.4 (95% C.I. 1.4, 79.7). These
      figures suggest a rapidly spreading epidemic, consistent with observations of the
      resurgence of tuberculosis in the United States in the 1980s and 1990s.

PMID- 16624909
TI  - Saccharomyces cerevisiae donor preference during mating-type switching is
      dependent on chromosome architecture and organization.
AB  - Saccharomyces mating-type (MAT) switching occurs by gene conversion using one of
      two donors, HMLalpha and HMRa, located near the ends of the same chromosome. MATa
      cells preferentially choose HMLalpha, a decision that depends on the
      recombination enhancer (RE) that controls recombination along the left arm of
      chromosome III (III-L). When RE is inactive, the two chromosome arms constitute
      separate domains inaccessible to each other; thus HMRa, located on the same arm
      as MAT, becomes the default donor. Activation of RE increases HMLalpha usage,
      even when RE is moved 50 kb closer to the centromere. If MAT is inserted into the
      same domain as HML, RE plays little or no role in activating HML, thus ruling out
      any role for RE in remodeling the silent chromatin of HML in regulating donor
      preference. When the donors MAT and RE are moved to chromosome V, RE increases
      HML usage, but the inaccessibility of HML without RE apparently depends on other
      chromosome III-specific sequences. Similar conclusions were reached when RE was
      placed adjacent to leu2 or arg4 sequences engaged in spontaneous recombination.
      We propose that RE's targets are anchor sites that tether chromosome III-L in
      MATalpha cells thus reducing its mobility in the nucleus.

PMID- 16624910
TI  - Amplified fragment length polymorphism mapping of quantitative trait loci for
      malaria parasite susceptibility in the yellow fever mosquito Aedes aegypti.
AB  - The yellow fever mosquito Aedes aegypti has been the subject of extensive genetic
      research due to its medical importance and the ease with which it can be
      manipulated in the laboratory. A molecular genetic linkage map was constructed
      using 148 amplified fragment length polymorphism (AFLP) and six single-strand
      conformation polymorphism (SSCP) markers. Eighteen AFLP primer combinations were
      used to genotype two reciprocal F2 segregating populations. Each primer
      combination generated an average of 8.2 AFLP markers eligible for linkage
      mapping. The length of the integrated map was 180.9 cM, giving an average marker
      resolution of 1.2 cM. Composite interval mapping revealed a total of six QTL
      significantly affecting Plasmodium susceptibility in the two reciprocal crosses
      of Ae. aegypti. Two common QTL on linkage group 2 were identified in both crosses
      that had similar effects on the phenotype, and four QTL were unique to each
      cross. In one cross, the four main QTL accounted for 64% of the total phenotypic
      variance, and digenic epistasis explained 11.8% of the variance. In the second
      cross, the four main QTL explained 66% of the variance, and digenic epistasis
      accounted for 16% of the variance. The actions of these QTL were either dominance
      or underdominance. Our results indicated that at least three new QTL were mapped
      on chromosomes 1 and 3. The polygenic nature of susceptibility to P. gallinaceum
      and epistasis are important factors for significant variation within or among
      mosquito strains. The new map provides additional information useful for further
      genetic investigation, such as identification of new genes and positional
      cloning.

PMID- 16624911
TI  - Genetic interactions among scribbler, Atrophin and groucho in Drosophila uncover
      links in transcriptional repression.
AB  - In eukaryotes, the ability of DNA-binding proteins to act as transcriptional
      repressors often requires that they recruit accessory proteins, known as
      corepressors, which provide the activity responsible for silencing transcription.
      Several of these factors have been identified, including the Groucho (Gro) and
      Atrophin (Atro) proteins in Drosophila. Here we demonstrate strong genetic
      interactions between gro and Atro and also with mutations in a third gene,
      scribbler (sbb), which encodes a nuclear protein of unknown function. We show
      that mutations in Atro and Sbb have similar phenotypes, including upregulation of
      the same genes in imaginal discs, which suggests that Sbb cooperates with Atro to
      provide repressive activity. Comparison of gro and Atro/sbb mutant phenotypes
      suggests that they do not function together, but instead that they may interact
      with the same transcription factors, including Engrailed and C15, to provide
      these proteins with maximal repressive activity.

PMID- 16624912
TI  - The Dunce cAMP phosphodiesterase PDE-4 negatively regulates G alpha(s)-dependent
      and G alpha(s)-independent cAMP pools in the Caenorhabditis elegans synaptic
      signaling network.
AB  - Forward genetic screens for mutations that rescue the paralysis of ric-8
      (Synembryn) reduction-of-function mutations frequently reveal mutations that
      cause hyperactivation of one or more components of the G alpha(s) pathway. Here,
      we report that one of these mutations strongly reduces the function of the Dunce
      cAMP phosphodiesterase PDE-4 by disrupting a conserved active site residue. Loss
      of function and neural overexpression of PDE-4 have profound and opposite effects
      on locomotion rate, but drug-response assays suggest that loss of PDE-4 function
      does not affect steady-state acetylcholine release or reception. Our genetic
      analysis suggests that PDE-4 regulates both G alpha(s)-dependent and G alpha(s)
      independent cAMP pools in the neurons controlling locomotion rate. By
      immunostaining, PDE-4 is strongly expressed throughout the nervous system, where
      it localizes to small regions at the outside boundaries of synaptic vesicle
      clusters as well as intersynaptic regions. The synaptic subregions containing PDE
      4 are distinct from those containing active zones, as indicated by costaining
      with an antibody against the long form of UNC-13. This highly focal subsynaptic
      localization suggests that PDE-4 may exert its effects by spatially regulating
      intrasynaptic cAMP pools.

PMID- 16624914
TI  - Inbreeding by environmental interactions affect gene expression in Drosophila
      melanogaster.
AB  - Genomewide gene expression patterns were investigated in inbred and noninbred
      Drosophila melanogaster lines under benign and stressful (high temperature)
      environmental conditions in a highly replicated experiment using Affymetrix gene
      chips. We found that both heat-shock protein and metabolism genes are strongly
      affected by temperature stress and that genes involved in metabolism are
      differentially expressed in inbred compared with noninbred lines, and that this
      effect is accentuated after heat stress exposure. Furthermore we show that
      inbreeding and temperature stress cause increased between-line variance in gene
      expression patterns. We conclude that inbreeding and environmental stress both
      independently and synergistically affect gene expression patterns. Interactions
      between inbreeding and the environment are often observed at the phenotypic level
      and our results reveal some of the genes that are involved at the individual gene
      level. Our observation of several metabolism genes being differentially expressed
      in inbred lines and more so after exposure to temperature stress, together with
      lower fitness in the investigated inbred lines, supports the hypothesis that
      superiority of heterozygous individuals partly derives from increased metabolic
      efficiency.

PMID- 16624913
TI  - Estimating the contribution of mutation, recombination and gene conversion in the
      generation of haplotypic diversity.
AB  - Recombination occurs through both homologous crossing over and homologous gene
      conversion during meiosis. The contribution of recombination relative to mutation
      is expected to be dramatically reduced in inbreeding organisms. We report
      coalescent-based estimates of the recombination parameter (rho) relative to
      estimates of the mutation parameter (theta) for 18 genes from the highly self
      fertilizing grass, wild barley, Hordeum vulgare ssp. spontaneum. Estimates of
      rho/theta are much greater than expected, with a mean rho/theta approximately
      1.5, similar to estimates from outcrossing species. We also estimate rho with and
      without the contribution of gene conversion. Genotyping errors can mimic the
      effect of gene conversion, upwardly biasing estimates of the role of conversion.
      Thus we report a novel method for identifying genotyping errors in nucleotide
      sequence data sets. We show that there is evidence for gene conversion in many
      large nucleotide sequence data sets including our data that have been purged of
      all detectable sequencing errors and in data sets from Drosophila melanogaster,
      D. simulans, and Zea mays. In total, 13 of 27 loci show evidence of gene
      conversion. For these loci, gene conversion is estimated to contribute an average
      of twice as much as crossing over to total recombination.

PMID- 16624915
TI  - Isolation of mutations that bypass the requirement of the septation initiation
      network for septum formation and conidiation in Aspergillus nidulans.
AB  - The kinase cascade of the septation initiation network (SIN), first revealed in
      fission yeast, activates the contraction of the actomyosin ring, and plays an
      essential role in fungal septation. Mob1p, an evolutionarily conserved SIN
      protein, is associated with the most downstream kinase of this cascade in fission
      yeast. In this study, the mobA gene encoding a homologous protein was isolated
      from the filamentous fungus Aspergillus nidulans, whose mycelium is made of
      multinucleate cells. The MOBA protein was required for septation and conidiation,
      but was not essential for hyphal extension and colony formation. To identify
      genes that act antagonistically against the SIN, UV mutagenesis was carried out
      to isolate suppressor (smo) mutations that restored conidiation when MOBA was not
      expressed. Microscopic examination indicated that the restored conidiation was
      concomitant with restored septation in the absence of the MOBA protein. Eight
      recessive smo mutations in five complementation groups also bypassed the
      requirement of the SIN kinases SEPH and SIDB for septum formation and
      conidiation. However, none of these smo mutations affected the localization of
      MOBA. Among smo mutations, smoA and smoB mutations caused reduced hyphal growth
      and colony formation. They also rendered hypersensitivity to low doses of the
      microtubule-depolymerizing agent benomyl for conidiation. Therefore, in A.
      nidulans, proteins encoded by the smo genes likely have an antagonistic
      interaction against the SIN pathway to regulate septation and conidiation.

PMID- 16624916
TI  - Concordant genetic estimators of migration reveal anthropogenically enhanced
      source-sink population structure in the river sculpin, Cottus gobio.
AB  - River systems are vulnerable to natural and anthropogenic habitat fragmentation
      and will often harbor populations deviating markedly from simplified theoretical
      models. We investigated fine-scale population structure in the sedentary river
      fish Cottus gobio using microsatellites and compared migration estimates from
      three FST estimators, a coalescent maximum-likelihood method and Bayesian recent
      migration analyses. Source-sink structure was evident via asymmetry in migration
      and genetic diversity with smaller upstream locations emigration biased and
      larger downstream subpopulations immigration biased. Patterns of isolation by
      distance suggested that the system was largely, but not entirely, in migration
      drift equilibrium, with headwater populations harboring a signal of past
      colonizations and in some cases also recent population bottlenecks. Up- vs.
      downstream asymmetry in population structure was partly attributable to the
      effects of flow direction, but was enhanced by weirs prohibiting compensatory
      upstream migration. Estimators of migration showed strong correspondence, at
      least in relative terms, especially if pairwise FST was used as an indirect index
      of relative gene flow rather than being translated to Nm. Since true parameter
      values are unknown in natural systems, comparisons among estimators are
      important, both to determine confidence in estimates of migration and to validate
      the performance of different methods.

PMID- 16624917
TI  - On the quantitative genetics of mixture characters.
AB  - Finite mixture models are helpful for uncovering heterogeneity due to hidden
      structure. Quantitative genetics issues of continuous characters having a finite
      mixture of Gaussian components as statistical distribution are explored in this
      article. The partition of variance in a mixture, the covariance between relatives
      under the supposition of an additive genetic model, and the offspring-parent
      regression are derived. Formulas for assessing the effect of mass selection
      operating on a mixture are given. Expressions for the genetic and phenotypic
      correlations between mixture and Gaussian traits and between two mixture traits
      are presented. It is found that, if there is heterogeneity in a population at the
      genetic or environmental level, then genetic parameters based on theory treating
      distributions as homogeneous can lead to misleading interpretations. Some
      peculiarities of mixture characters are: heritability depends on the mean values
      of the component distributions, the offspring-parent regression is nonlinear, and
      genetic or phenotypic correlations cannot be interpreted devoid of the mixture
      proportions and of the parameters of the distributions mixed.

PMID- 16624918
TI  - A coalescent-based estimator of admixture from DNA sequences.
AB  - A variety of estimators have been developed to use genetic marker information in
      inferring the admixture proportions (parental contributions) of a hybrid
      population. The majority of these estimators used allele frequency data, ignored
      molecular information that is available in markers such as microsatellites and
      DNA sequences, and assumed that mutations are absent since the admixture event.
      As a result, these estimators may fail to deliver an estimate or give rather poor
      estimates when admixture is ancient and thus mutations are not negligible. A
      previous molecular estimator based its inference of admixture proportions on the
      average coalescent times between pairs of genes taken from within and between
      populations. In this article I propose an estimator that considers the entire
      genealogy of all of the sampled genes and infers admixture proportions from the
      numbers of segregating sites in DNA sequence samples. By considering the
      genealogy of all sequences rather than pairs of sequences, this new estimator
      also allows the joint estimation of other interesting parameters in the admixture
      model, such as admixture time, divergence time, population size, and mutation
      rate. Comparative analyses of simulated data indicate that the new coalescent
      estimator generally yields better estimates of admixture proportions than the
      previous molecular estimator, especially when the parental populations are not
      highly differentiated. It also gives reasonably accurate estimates of other
      admixture parameters. A human mtDNA sequence data set was analyzed to demonstrate
      the method, and the analysis results are discussed and compared with those from
      previous studies.

PMID- 16624919
TI  - A genetic test of the role of the maternal pronucleus in Wolbachia-induced
      cytoplasmic incompatibility in Drosophila melanogaster.
AB  - Cytoplasmic incompatibility (CI) is a reproductive sterility found in arthropods
      that is caused by the endoparasitic bacteria Wolbachia. In CI, host progeny fail
      to develop during early embryogenesis if Wolbachia-infected males fertilize
      uninfected females. It is widely accepted that this lethality is caused by some
      unknown Wolbachia-induced modification of the paternal nuclear material in the
      host testes. However, the direct means by which this modification leads to early
      embryonic death are currently unresolved. Results from previous studies suggested
      that CI lethality occurs as a result of asynchrony in cell cycle timing between
      the paternal and maternal pronuclei. This hypothesis can be tested experimentally
      by the prediction that the Wolbachia-modified paternal pronucleus should support
      androgenetic development (i.e., from the paternal pronucleus only). Using
      specific mutations in Drosophila melanogaster that produce androgenetic progeny,
      we demonstrate that the Wolbachia-induced modification inhibits this type of
      development. This result suggests that CI occurs independently of the maternal
      pronucleus and argues against pronuclear asynchrony as the primary cause of CI
      lethality. We propose that CI occurs instead as the result of either a
      developmentally incompetent paternal pronucleus or asynchrony between the
      paternal pronucleus and the cell cycle of the egg cytoplasm.

PMID- 16624920
TI  - The hitchhiking effect of an autosomal meiotic drive gene.
AB  - Transmission-ratio distortion is a departure from a 1:1 segregation of alleles in
      the gametes of a heterozygous individual. The so-called driving allele is
      strongly selected regardless of its effect on the fitness of the carrying
      individual. It may then have an important impact on neutral polymorphism due to
      the genetic hitchhiking effect. We study this hitchhiking effect in the case of
      true meiotic drive in autosomes and show that it is more dependent on the
      recombination rate than in the classical case of a gene positively selected at
      the organism level.

PMID- 16624921
TI  - Segregating variation in the transcriptome: cis regulation and additivity of
      effects.
AB  - Properties of genes underlying variation in complex traits are largely unknown,
      especially for variation that segregates within populations. Here, we evaluate
      allelic effects, cis and trans regulation, and dominance patterns of transcripts
      that are genetically variable in a natural population of Drosophila melanogaster.
      Our results indicate that genetic variation due to the third chromosome causes
      mainly additive and nearly additive effects on gene expression, that cis and
      trans effects on gene expression are numerically about equal, and that cis
      effects account for more genetic variation than do trans effects. We also
      evaluated patterns of variation in different functional categories and determined
      that genes involved in metabolic processes are overrepresented among variable
      transcripts, but those involved in development, transcription regulation, and
      signal transduction are underrepresented. However, transcripts for proteins known
      to be involved in protein-protein interactions are proportionally represented
      among variable transcripts.

PMID- 16624922
TI  - Deleterious epistatic interactions between electron transport system protein
      coding loci in the copepod Tigriopus californicus.
AB  - The nature of epistatic interactions between genes encoding interacting proteins
      in hybrid organisms can have important implications for the evolution of
      postzygotic reproductive isolation and speciation. At this point very little is
      known about the fitness differences caused by specific closely interacting but
      evolutionarily divergent proteins in hybrids between populations or species. The
      intertidal copepod Tigriopus californicus provides an excellent model in which to
      study such interactions because the species range includes numerous genetically
      divergent populations that are still capable of being crossed in the laboratory.
      Here, the effect on fitness due to the interactions of three complex III proteins
      of the electron transport system in F2 hybrid copepods resulting from crosses of
      a pair of divergent populations is examined. Significant deviations from
      Mendelian inheritance are observed for each of the three genes in F2 hybrid
      adults but not in nauplii (larvae). The two-way interactions between these genes
      also have a significant impact upon the viability of these hybrid copepods.
      Dominance appears to play an important role in mediating the interactions between
      these loci as deviations are caused by heterozygote/homozygote deleterious
      interactions. These results suggest that the fitness consequences of the
      interactions of these three complex III-associated genes could influence
      reproductive isolation in this system.

PMID- 16624923
TI  - Fission yeast Num1p is a cortical factor anchoring dynein and is essential for
      the horse-tail nuclear movement during meiotic prophase.
AB  - During meiotic prophase in the fission yeast Schizosaccharomyces pombe, the
      nucleus oscillates between the two ends of a cell. This oscillatory nuclear
      movement is important to promote accurate pairing of homologous chromosomes and
      requires cytoplasmic dynein. Dynein accumulates at the points where microtubule
      plus ends contact the cell cortex and generate a force to drive nuclear
      oscillation. However, it remains poorly understood how dynein associates with the
      cell cortex. Here we show that S. pombe Num1p functions as a cortical-anchoring
      factor for dynein. Num1p is expressed in a meiosis-specific manner and localized
      to the cell cortex through its C-terminal PH domain. The num1 deletion mutant
      shows microtubule dynamics comparable to that in the wild type. However, it lacks
      cortical accumulation of dynein and is defective in the nuclear oscillation as is
      the case for the dynein mutant. We also show that Num1p can recruit dynein
      independently of the CLIP-170 homolog Tip1p.

PMID- 16624924
TI  - On locating multiple interacting quantitative trait loci in intercross designs.
AB  - A modified version (mBIC) of the Bayesian Information Criterion (BIC) has been
      previously proposed for backcross designs to locate multiple interacting
      quantitative trait loci. In this article, we extend the method to intercross
      designs. We also propose two modifications of the mBIC. First we investigate a
      two-stage procedure in the spirit of empirical Bayes methods involving an
      adaptive (i.e., data-based) choice of the penalty. The purpose of the second
      modification is to increase the power of detecting epistasis effects at loci
      where main effects have already been detected. We investigate the proposed
      methods by computer simulations under a wide range of realistic genetic models,
      with nonequidistant marker spacings and missing data. In the case of large
      intermarker distances we use imputations according to Haley and Knott regression
      to reduce the distance between searched positions to not more than 10 cM. Haley
      and Knott regression is also used to handle missing data. The simulation study as
      well as real data analyses demonstrates good properties of the proposed method of
      QTL detection.

PMID- 16624925
TI  - Two-stage designs in case-control association analysis.
AB  - DNA pooling is a cost-effective approach for collecting information on marker
      allele frequency in genetic studies. It is often suggested as a screening tool to
      identify a subset of candidate markers from a very large number of markers to be
      followed up by more accurate and informative individual genotyping. In this
      article, we investigate several statistical properties and design issues related
      to this two-stage design, including the selection of the candidate markers for
      second-stage analysis, statistical power of this design, and the probability that
      truly disease-associated markers are ranked among the top after second-stage
      analysis. We have derived analytical results on the proportion of markers to be
      selected for second-stage analysis. For example, to detect disease-associated
      markers with an allele frequency difference of 0.05 between the cases and
      controls through an initial sample of 1000 cases and 1000 controls, our results
      suggest that when the measurement errors are small (0.005), approximately 3% of
      the markers should be selected. For the statistical power to identify disease
      associated markers, we find that the measurement errors associated with DNA
      pooling have little effect on its power. This is in contrast to the one-stage
      pooling scheme where measurement errors may have large effect on statistical
      power. As for the probability that the disease-associated markers are ranked
      among the top in the second stage, we show that there is a high probability that
      at least one disease-associated marker is ranked among the top when the allele
      frequency differences between the cases and controls are not <0.05 for reasonably
      large sample sizes, even though the errors associated with DNA pooling in the
      first stage are not small. Therefore, the two-stage design with DNA pooling as a
      screening tool offers an efficient strategy in genomewide association studies,
      even when the measurement errors associated with DNA pooling are nonnegligible.
      For any disease model, we find that all the statistical results essentially
      depend on the population allele frequency and the allele frequency differences
      between the cases and controls at the disease-associated markers. The general
      conclusions hold whether the second stage uses an entirely independent sample or
      includes both the samples used in the first stage and an independent set of
      samples.

PMID- 16624927
TI  - The continuing challenge of anti-neutrophil cytoplasm antibody-associated
      systemic vasculitis and glomerulonephritis.

PMID- 16624926
TI  - Comparison of the genome structure of the self-incompatibility (S) locus in
      interspecific pairs of S haplotypes.
AB  - The determinants of recognition specificity of self-incompatibility in Brassica
      are SRK in the stigma and SP11/SCR in the pollen, both of which are encoded in
      the S locus. The nucleotide sequence analyses of many SRK and SP11/SCR alleles
      have identified several interspecific pairs of S haplotypes having highly similar
      sequences between B. oleracea and B. rapa. These interspecific pairs of S
      haplotypes are considered to be derived from common ancestors and to have
      maintained the same recognition specificity after speciation. In this study, the
      genome structures of three interspecific pairs of S haplotypes were compared by
      sequencing SRK, SP11/SCR, and their flanking regions. Regions between SRK and
      SP11/SCR in B. oleracea were demonstrated to be much longer than those of B. rapa
      and several retrotransposon-like sequences were identified in the S locus in B.
      oleracea. Among the seven retrotransposon-like sequences, six sequences were
      found to belong to the ty3 gypsy group. The gag sequences of the retrotransposon
      like sequences were phylogenetically different from each other. In Southern blot
      analysis using retrotransposon-like sequences as probes, the B. oleracea genome
      showed more signals than the B. rapa genome did. These findings suggest a role
      for the S locus and genome evolution in self-incompatible plant species.

PMID- 16624928
TI  - Is there a role for TNF-alpha in anti-neutrophil cytoplasmic antibody-associated
      vasculitis? Lessons from other chronic inflammatory diseases.
AB  - Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most
      common cause of rapidly progressive glomerulonephritis and immune-mediated
      pulmonary renal syndrome. Now that the acute manifestations of the disease
      generally can be controlled with immunosuppressive drugs, ANCA-associated
      vasculitis has become a chronic and relapsing inflammatory disorder. The need to
      develop safer and more effective treatment has led to great interest in the
      mediators of chronic inflammation. There are many lessons to be learned from
      studies of other chronic inflammatory diseases, particularly rheumatoid arthritis
      (RA). The identification of a TNF-alpha-dependent cytokine cascade in the in
      vitro cultures of synovium in joints of patients with RA led to studies of TNF
      blockade in experimental models of arthritis and subsequently to clinical trials.
      These have culminated in the widespread introduction of anti-TNF therapy not only
      in RA but also in Crohn disease, ankylosing spondylitis, and several other
      chronic inflammatory disorders. Following a similar investigative pathway,
      studies that show the importance of TNF production by leukocytes and intrinsic
      renal cells in glomerulonephritis have been followed by the demonstration of the
      effectiveness of TNF blockade in several experimental models of
      glomerulonephritis and vasculitis. In experimental autoimmune vasculitis,
      improvement in disease was paralleled by a reduction in leukocyte transmigration,
      as demonstrated by intravital microscopy. The benefit of infliximab (a mAb to
      TNF) in ANCA-associated vasculitis was recently reported in a prospective open
      label study. However, the use of etanercept (a soluble TNF receptor fusion
      protein) was not found to be of significant benefit in a randomized, controlled
      trial in patients with Wegener granulomatosis. Therefore, there is a need for
      further evaluation of the use of anti-TNF antibodies in patients with ANCA
      associated glomerulonephritis.

PMID- 16624929
TI  - Pathogenesis of vascular inflammation by anti-neutrophil cytoplasmic antibodies.
AB  - The reports of a newborn who developed glomerulonephritis and pulmonary
      hemorrhage after transplacental transfer of anti-neutrophil cytoplasmic antibody
      (ANCA) IgG with specificity for myeloperoxidase (MPO) is compelling clinical
      evidence that ANCA are pathogenic. In vitro studies indicate that ANCA activate
      cytokine-primed neutrophils and monocytes through both direct Fab'2 binding and
      Fc receptor engagement. Neutrophils that have been activated by ANCA release
      oxygen radicals, lytic enzymes, and inflammatory cytokines and adhere to and kill
      endothelial cells. A murine model caused by passive administration of mouse anti
      mouse MPO IgG provides convincing evidence that ANCA IgG alone in the absence of
      antigen-specific T cells can cause necrotizing glomerulonephritis and vasculitis.
      This pathogenic process is enhanced by synergistic inflammatory factors, probably
      through priming of neutrophils. Immunization of rats with human MPO induces
      antibodies that cross-react with rat MPO and cause glomerulonephritis and
      vasculitis. These ANCA act in concert with chemokines to cause adherence of
      leukocytes to the walls of small vessels with subsequent injury. To date, animal
      models of disease that is induced by anti-proteinase 3 are less robust. Clinical
      and experimental data suggest but do not prove that the ANCA autoimmune response
      is initiated by an immune response to an antisense peptide of the ANCA antigen or
      its mimic that may be introduced into the body by an infectious pathogen. This
      antibody response elicits anti-idiotypic antibodies that cross-react with ANCA
      antigens. The pathogenesis of ANCA disease is multifactorial, with genetic and
      environmental factors influencing onset of the autoimmune response, the mediation
      of acute injury, and the induction of the chronic response to injury.

PMID- 16624930
TI  - T cells in crescentic glomerulonephritis.
AB  - Crescent formation in glomerulonephritis (GN) is a manifestation of severe
      glomerular injury that usually results in a poor clinical outcome. In humans,
      crescentic GN is frequently associated with evidence of either systemic or organ
      specific autoimmunity. T cells play a major role in initiation of adaptive immune
      responses that lead to crescentic injury. In experimental models of crescentic
      GN, Th1 predominant immune responses have been shown to promote crescent
      formation. Perturbation of regulatory T cell function may contribute to
      development of autoimmune crescentic GN. The presence of T cells and macrophages
      in crescentic glomeruli, frequently in the absence of humoral mediators of
      immunity, suggest a dominant effector role for T cells in crescentic GN. The
      association of cellular immune mediators with local fibrin deposition implicates
      cell-mediated "delayed-type hypersensitivity-like" mechanisms in crescent
      formation. Intrinsic renal cells also contribute to T cell-driven effector
      mechanisms in crescentic GN, via expression of MHC II and co-stimulatory
      molecules and by production of chemokines and cytokines that amplify leukocyte
      recruitment and injury.

PMID- 16624931
TI  - Anti-neutrophil cytoplasm-associated glomerulonephritis.
AB  - Wegener's granulomatosis, microscopic polyangiitis, and renal limited vasculitis
      are associated with circulating anti-neutrophil cytoplasm antibodies and are an
      important cause of rapidly progressive glomerulonephritis. This review gives an
      account of recent advances in the understanding of the pathogenesis underlying
      these conditions and how these may lead to future treatments. Consideration is
      given to recent clinical trials in the management of anti-neutrophil cytoplasm
      antibodies (ANCA)-associated vasculitides.

PMID- 16624932
TI  - Differential responsiveness to IFN-alpha and IFN-beta of human mature DC through
      modulation of IFNAR expression.
AB  - In human monocyte-derived dendritic cells (DC), infection with Mycobacterium
      tuberculosis and viruses or stimulation with Toll-like receptor type 3 and 4
      agonists causes the release of type I interferon (IFN). Here, we describe that
      the IFN-beta released upon stimulation with lipopolysaccharide (LPS) or
      polyinosinic:polycytidylic acid (poly I:C) is responsible for a rapid and
      sustained signal transducer and activator of transcription 1 and 2 activation and
      expression of IFN-stimulated genes, such as the transcription factor IFN
      regulatory factor 7 and the chemokine CXC chemokine ligand 10. The autocrine
      production of IFN-beta from LPS and poly I:C-matured DC (mDC) induced a temporary
      saturation of the response to type I IFN and a marked decline in the level of the
      two IFN receptor (IFNAR) subunits. It is interesting that we found that upon
      clearing of the released cytokines, LPS-stimulated DC reacquired full
      responsiveness to IFN-beta but only partial responsiveness to IFN-alpha, and
      their maturation process was unaffected. Monitoring of surface and total levels
      of the receptor subunits showed that maximal expression of IFNAR2 resumed within
      24 h of clearing, and IFNAR1 expression remained low. Thus, mDC can modulate
      their sensitivity to two IFN subtypes through a differential regulation of the
      IFNAR subunits.

PMID- 16624933
TI  - Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in
      human neutrophils.
AB  - Cyclooxygenase (COX) is a key enzyme in prostaglandin (PG) synthesis. Up
      regulation of its COX-2 isoform is responsible for the increased PG release,
      taking place under inflammatory conditions, and also, is thought to be involved
      in allergic and inflammatory diseases. In the present work, we demonstrate that
      COX-2 expression becomes highly induced by anti-immunoglobulin E (IgE) antibodies
      and by antigens in human neutrophils from allergic patients. This induction was
      detected at mRNA and protein levels and was accompanied by a concomitant PGE(2)
      and thromboxane A(2) release. We also show evidence that inhibitors of reduced
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, such as 4-(2
      aminoethyl)benzenesulphonyl fluoride and 4-hydroxy-3-methoxyaceto-phenone,
      completely cancelled anti-IgE-induced COX-2 protein up-regulation, suggesting
      that this process is mediated by reactive oxygen species (ROS) derived from NADPH
      oxidase activity. Moreover, the mitogen-activated protein kinases (MAPKs), p38
      and extracellular signal-regulated kinase, and also, the transcription factor,
      nuclear factor (NF)-kappaB, are involved in the up-regulation of COX-2
      expression, as specific chemical inhibitors of these two kinases, such as
      SB203580 and PD098059, and of the NF-kappaB pathway, such as N(alpha)
      benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal, abolished IgE-dependent COX-2
      induction. Evidence is also presented, using Fe(2)(+)/Cu(2)(+) ions, that
      hydroxyl radicals generated from hydrogen peroxide through Fenton reactions could
      constitute candidate modulators able to directly trigger anti-IgE-elicited COX-2
      expression through MAPK and NF-kappaB pathways. Present results underscore a new
      role for ROS as second messengers in the modulation of COX-2 expression by human
      neutrophils in allergic conditions.

PMID- 16624934
TI  - Modulation of cell cycle progression by CTLA4-CD80/CD86 interactions on CD4+ T
      cells depends on strength of the CD3 signal: critical role for IL-2.
AB  - Cytotoxic T-lymphocyte antigen 4 (CTLA4) is a well-studied T cell costimulatory
      receptor that is known to inhibit T cell activation. In this study, the
      relationship between strength of the first signal and costimulatory interactions
      on primary mouse CD4(+) T cells was investigated. CTLA4-CD80/CD86 interactions
      differentially modulate T cell cycling based on the mode of CD3 signal:
      Activation with plate-bound (pb) anti-CD3 generates a strong signal compared with
      a weak signal with soluble (sol) anti-CD3, resulting in approximately sevenfold
      higher amounts of interleukin (IL)-2 and an increase in cell cycling. Activation
      of T cells with sol anti-CD3 (weak signal) together with CTLA4-CD80/CD86 blockade
      lowers IL-2 production and cell cycling, demonstrating an enhancing role for
      these interactions. Conversely, blockade of CTLA4-CD80/CD86 interactions on T
      cells activated with pb anti-CD3 (strong signal) increases proliferation, which
      is consistent with CTLA4 as a negative regulator. Also, coculture of T cells with
      Chinese hamster ovary cells expressing CD80 or CD86 demonstrates that the
      strength of the primary signal plays an important role. It is important that
      modulation of IL-2 amounts leads to distinct alterations in the functional
      effects of CTLA4-CD80/CD86 interactions. On increasing IL-2 amounts, activation
      of T cells stimulated with sol anti-CD3 (weak signal) and CTLA4-CD80/CD86
      blockade is greater compared with control. Concurrently, neutralization of IL-2
      greatly reduces activation of T cells stimulated with pb anti-CD3 (strong signal)
      and CTLA4-CD80/CD86 blockade compared with control. These results underscore the
      importance of strength of first signal, CTLA4-CD80/CD86 interactions, and IL-2
      amounts in modulating primary CD4(+) T cell responses.

PMID- 16624935
TI  - Overloading of stable and exclusion of unstable human superoxide dismutase-1
      variants in mitochondria of murine amyotrophic lateral sclerosis models.
AB  - Mutants of human superoxide dismutase-1 (hSOD1) cause amyotrophic lateral
      sclerosis (ALS), and mitochondria are thought to be primary targets of the
      cytotoxic action. The high expression rates of hSOD1s in transgenic ALS models
      give high levels of the stable mutants G93A and D90A as well as the wild-type
      human enzyme, significant proportions of which lack Cu and the intrasubunit
      disulfide bond. The endogenous murine SOD1 (mSOD1) also lacks Cu and is disulfide
      reduced but is active and oxidized in mice expressing the low-level unstable
      mutants G85R and G127insTGGG. The possibility that the molecular alterations may
      cause artificial loading of the stable hSOD1s into mitochondria was explored.
      Approximately 10% of these hSOD1s were localized to mitochondria, reaching levels
      100-fold higher than those of mSOD1 in control mice. There was no difference
      between brain and spinal cord and between stable mutants and the wild-type hSOD1.
      mSOD1 was increased fourfold in mitochondria from high-level hSOD1 mice but was
      normal in those with low levels, suggesting that the Cu deficiency and disulfide
      reduction cause mitochondrial overloading. The levels of G85R and G127insTGGG
      mutant hSOD1s in mitochondria were 100- and 1000-fold lower than those of stable
      mutants. Spinal cords from symptomatic mice contained hSOD1 aggregates covering
      the entire density gradient, which could contaminate isolated organelle
      fractions. Thus, high hSOD1 expression rates can cause artificial loading of
      mitochondria. Unstable low-level hSOD1s are excluded from mitochondria,
      indicating other primary locations of injury. Such models may be preferable for
      studies of ALS pathogenesis.

PMID- 16624936
TI  - Synaptic basis for whisker deprivation-induced synaptic depression in rat
      somatosensory cortex.
AB  - Whisker deprivation weakens excitatory layer 4 (L4) inputs to L2/3 pyramidal
      cells in rat primary somatosensory (S1) cortex, which is likely to contribute to
      whisker map plasticity. This weakening has been proposed to represent long-term
      depression (LTD) induced by sensory deprivation in vivo. Here, we studied the
      synaptic expression mechanisms for deprivation-induced weakening of L4-L2/3
      inputs and assessed its similarity to LTD, which is known to be expressed
      presynaptically at L4-L2/3 synapses. Whisker deprivation increased the paired
      pulse ratio at L4-L2/3 synapses and slowed the use-dependent block of NMDA
      receptor currents by MK-801 [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine maleate], indicating that deprivation reduced
      transmitter release probability at these synapses. In contrast, deprivation did
      not alter either miniature EPSC amplitude in L2/3 neurons or the amplitude of
      quantal L4-L2/3 synaptic responses measured in strontium, indicating that
      postsynaptic responsiveness was unchanged. In young postnatal day 12 (P12) rats,
      at least 4 d of deprivation were required to significantly weaken L4-L2/3
      synapses. Similar weakening occurred when deprivation began at older ages (P20),
      when synapses are mostly mature, indicating that weakening is unlikely to
      represent a failure of synaptic maturation but instead represents a reduction in
      the strength of existing synapses. Thus, whisker deprivation weakens L4-L2/3
      synapses by decreasing presynaptic function, similar to known LTD mechanisms at
      this synapse.

PMID- 16624938
TI  - Rapid, activity-dependent plasticity in timing precision in neonatal barrel
      cortex.
AB  - Developing neuronal networks acquire the ability to precisely time events, a key
      feature required for information processing. In the barrel cortex, encoding of
      information requires a high-precision temporal code with a resolution of
      approximately 5 ms; however, it is not known what process drives the maturation
      in timing precision. Here, we report that long-term potentiation (LTP) at
      thalamocortical synapses in the neonatal layer IV barrel cortex produces a
      dramatic improvement in the timing of neuronal output and synaptic input. LTP
      strongly reduces the latency and variability of synaptically evoked action
      potentials, improving the fidelity of timing to within that predicted to be
      required for adult sensory processing. Such changes in timing also occur during
      development in the neonate. LTP also reduces the summation of EPSPs shortening
      the window for coincidence detection for synaptic input. In contrast to these
      reliable effects, LTP produced only a modest and variable change in synaptic
      efficacy. Thus, our findings suggest that the primary role of this form of
      neonatal LTP is for the acquisition of timing precision and the refinement of
      coincidence detection, rather than an increase in synaptic strength. Therefore,
      neonatal thalamocortical LTP may be a critical prerequisite for the maturation of
      information processing in the barrel cortex.

PMID- 16624937
TI  - Two coincidence detectors for spike timing-dependent plasticity in somatosensory
      cortex.
AB  - Many cortical synapses exhibit spike timing-dependent plasticity (STDP) in which
      the precise timing of presynaptic and postsynaptic spikes induces synaptic
      strengthening [long-term potentiation (LTP)] or weakening [long-term depression
      (LTD)]. Standard models posit a single, postsynaptic, NMDA receptor-based
      coincidence detector for LTP and LTD components of STDP. We show instead that
      STDP at layer 4 to layer 2/3 synapses in somatosensory (S1) cortex involves
      separate calcium sources and coincidence detection mechanisms for LTP and LTD.
      LTP showed classical NMDA receptor dependence. LTD was independent of
      postsynaptic NMDA receptors and instead required group I metabotropic glutamate
      receptors and calcium from voltage-sensitive channels and IP3 receptor-gated
      stores. Downstream of postsynaptic calcium, LTD required retrograde
      endocannabinoid signaling, leading to presynaptic LTD expression, and also
      required activation of apparently presynaptic NMDA receptors. These LTP and LTD
      mechanisms detected firing coincidence on approximately 25 and approximately 125
      ms time scales, respectively, and combined to implement the overall STDP rule.
      These findings indicate that STDP is not a unitary process and suggest that
      endocannabinoid-dependent LTD may be relevant to cortical map plasticity.

PMID- 16624939
TI  - Why does the brain predict sensory consequences of oculomotor commands? Optimal
      integration of the predicted and the actual sensory feedback.
AB  - When the brain initiates a saccade, it uses a copy of the oculomotor commands to
      predict the visual consequences: for example, if one fixates a reach target, a
      peripheral saccade will produce an internal estimate of the new retinal location
      of the target, a process called remapping. In natural settings, the target likely
      remains visible after the saccade. So why should the brain predict the sensory
      consequence of the saccade when after its completion, the image of the target
      remains visible? We hypothesized that in the post-saccadic period, the brain
      integrates target position information from two sources: one based on remapping
      and another based on the peripheral view of the target. The integration of
      information from these two sources could produce a less variable target estimate
      than is possible from either source alone. Here, we show that reaching toward
      targets that were initially foveated and remapped had significantly less variance
      than reaches relying on peripheral target information. Furthermore, in a more
      natural setting where both sources of information were available simultaneously,
      variance of the reaches was further reduced as predicted by integration. This
      integration occurred in a statistically optimal manner, as demonstrated by the
      change in integration weights when we manipulated the uncertainty of the post
      saccadic target estimate by varying exposure time. Therefore, the brain predicts
      the sensory consequences of motor commands because it integrates its prediction
      with the actual sensory information to produce an estimate of sensory space that
      is better than possible from either source alone.

PMID- 16624940
TI  - Pathway-specific bidirectional regulation of Ca2+/calmodulin-dependent protein
      kinase II at spinal nociceptive synapses after acute noxious stimulation.
AB  - An intensely painful stimulus may lead to hyperalgesia, the enhanced sensation of
      subsequent painful stimuli. This is commonly believed to involve facilitated
      transmission of sensory signals in the spinal cord, possibly by a long-term
      potentiation-like mechanism. However, plasticity of identified synapses in intact
      hyperalgesic animals has not been reported. Here, we show, using neuronal tracing
      and postembedding immunogold labeling, that after acute noxious stimulation
      (hindpaw capsaicin injections), immunolabeling of Ca2+/calmodulin-dependent
      protein kinase II (CaMKII) and of CaMKII phosphorylated at Thr(286/287) (pCaMKII)
      are upregulated postsynaptically at synapses established by peptidergic primary
      afferent fibers in the superficial dorsal horn of intact rats. In contrast,
      postsynaptic pCaMKII immunoreactivity was instead downregulated at synapses of
      nonpeptidergic primary afferent C-fibers; this loss of pCaMKII immunolabel
      occurred selectively at distances greater than approximately 20 nm from the
      postsynaptic membrane and was accompanied by a smaller reduction in total CaMKII
      contents of these synapses. Both pCaMKII and CaMKII immunogold labeling were
      unaffected at synapses formed by presumed low-threshold mechanosensitive afferent
      fibers. Thus, distinct molecular modifications, likely indicative of plasticity
      of synaptic strength, are induced at different populations of presumed
      nociceptive primary afferent synapse by intense noxious stimulation, suggesting a
      complex modulation of parallel nociceptive pathways in inflammatory hyperalgesia.
      Furthermore, the activity-induced loss of certain postsynaptic pools of
      autophosphorylated CaMKII at previously unmanipulated synapses supports a role
      for the kinase in basal postsynaptic function.

PMID- 16624941
TI  - Light-induced changes in spike synchronization between coupled ON direction
      selective ganglion cells in the mammalian retina.
AB  - Although electrical coupling via gap junctions is prevalent among ganglion cells
      in the vertebrate retina, there have been few direct studies of their influence
      on the light-evoked signaling of these cells. Here, we describe the pattern and
      function of coupling between the ON direction selective (DS) ganglion cells, a
      unique subtype whose signals are transmitted to the accessory optic system (AOS)
      where they initiate the optokinetic response. ON DS cells are coupled indirectly
      via gap junctions made with a subtype of polyaxonal amacrine cell. This coupling
      underlies synchronization of the spontaneous and light-evoked spike activity of
      neighboring ON DS cells. However, we find that ON DS cell pairs show robust
      synchrony for all directions of stimulus movement, except for the null direction.
      Null stimulus movement evokes a GABAergic inhibition that temporally shifts
      firing of ON DS cell neighbors, resulting in a desynchronization of spike
      activity. Thus, detection of null stimulus movement appears key to the direction
      selectivity of ON DS cells, evoking both an attenuation of spike frequency and a
      desynchronization of neighbors. We posit that active desynchronization reduces
      summation of synaptic potentials at target AOS cells and thus provides a
      secondary mechanism by which ON DS cell ensembles can signal direction of
      stimulus motion to the brain.

PMID- 16624942
TI  - Ambient GABA constrains the strength of GABAergic synapses at Cajal-Retzius cells
      in the developing visual cortex.
AB  - At early stages of brain development, GABA plays a dual role. It fulfills
      important trophic functions and provides a major excitatory drive for the
      immature neuronal network. Here, we investigated whether GABA itself can limit
      the strength of excitatory GABAergic synapses on Cajal-Retzius (CR) cells in
      sagittal slices from the mouse visual cortex. (2S)-3-[[(1S)-1-(3,4
      dichlorophenyl)ethyl]amino-2-hydroxypropyl](phenylmethyl)phosphinic acid
      (CGP55845), a specific GABAB receptor (GABABR) blocker, increased the frequency
      of spontaneous Ca2+ transients and spontaneous and miniature IPSCs (mIPSCs) but
      did not affect mIPSC amplitudes or kinetics. CGP55845 significantly increased
      evoked IPSC (eIPSC) amplitudes and decreased the paired-pulse ratio (PPR).
      Baclofen, a specific GABABR agonist, produced opposite effects. The size of the
      readily releasable pool was not affected by these GABABR modulators. The same
      CGP55845 actions were observed at physiological temperatures, but they were
      abolished after glutamate decarboxylase block with 3-mercaptopropionic acid (3
      MP). These results indicate that presynaptic GABABRs dynamically regulate GABA
      release probability. SNAP-5114, a specific GABA transporter-2/3 (GAT-2/3)
      blocker, enhanced mIPSC frequencies, decreased PPR, and increased eIPSC
      amplitudes without changing eIPSC kinetics. These effects were blocked by
      CGP55845 and 3-MP. NO-711, a specific GAT-1 blocker, prolonged eIPSC decay and
      decreased eIPSC/mIPSC amplitudes. These NO-711-mediated effects were not
      sensitive to CGP55845 and 3-MP. We conclude that the strength of GABAergic inputs
      to CR cells is constrained by GABABRs that are persistently activated by ambient
      GABA. The latter is also provided by GAT-2/3 operating in the reversed mode.
      Presynaptic GAT-1 functions in the uptake mode and possibly provides GABA for
      presynaptic vesicle filling.

PMID- 16624943
TI  - Contribution of the monkey frontal eye field to covert visual attention.
AB  - The frontal eye field (FEF) has long been regarded as a cortical area critically
      involved in the execution of voluntary saccadic eye movements. However, recent
      studies have suggested that the FEF may also play a role in orienting attention.
      To address this issue, we reversibly inactivated the FEF using multiple
      microinjections of muscimol, a GABAA agonist, in two macaque monkeys performing
      visually guided saccades to a single target. The effects of FEF inactivation were
      also studied in a covert visual search task that required monkeys to search for a
      target presented among several distractors without making any eye movements. As
      expected, inactivating the FEF caused spatially selective deficits in executing
      visually guided saccades, but it also altered the ability to detect a visual
      target presented among distractors when no eye movements were permitted. These
      results allow us to conclude definitively to an involvement of the FEF in both
      oculomotor and attentional functions. Comparison of the present results with a
      similar experiment conducted in the lateral intraparietal cortex area revealed
      qualitatively different deficits, suggesting that the two areas may make distinct
      contributions to selective attention processes.

PMID- 16624944
TI  - Reversal of brain injury-induced prefrontal glutamic acid decarboxylase
      expression and working memory deficits by D1 receptor antagonism.
AB  - Working memory (WM), the ability to transiently hold information in mind, is
      essential for high-level cognitive functions that are often impaired in brain
      injured patients. The cellular and molecular mechanisms contributing to WM
      deficits, which can manifest in the absence of overt damage, in these patients
      are unknown. The function of the dorsolateral prefrontal cortex in humans and
      monkeys, and the medial prefrontal cortex (mPFC), in rodents is critical for WM.
      We demonstrate that controlled cortical impact injury of rats causes a long
      lasting WM impairment that is associated with increased levels of the GABA
      synthesizing enzyme glutamic acid decarboxylase 67 (GAD67) in the mPFC for up to
      1 month after injury. A single administration of dopamine D1 antagonists at 14 d
      after injury is sufficient to decrease GAD67 levels and restore WM for at least 1
      week. These findings indicate that inhibition of prefrontal neuronal activity
      contributes to WM deficits and that strategies to reduce GAD67 expression can
      offer prolonged WM improvement in brain-injured patients.

PMID- 16624945
TI  - Intrinsic and synaptic dynamics interact to generate emergent patterns of
      rhythmic bursting in thalamocortical neurons.
AB  - Rhythmic inhibition entrains the firing of excitatory neurons during oscillations
      throughout the brain. Previous work has suggested that the strength and duration
      of inhibitory input determines the synchrony and period, respectively, of these
      oscillations. In particular, sleep spindles result from a cycle of events
      including rhythmic inhibition and rebound bursts in thalamocortical (TC) neurons,
      and slowing and strengthening this inhibitory input may transform spindles into
      spike-wave discharges characteristic of absence epilepsy. Here, we used dynamic
      clamp to inject TC neurons with spindle-like trains of IPSCs and studied how
      modest changes in the amplitude and/or duration of these IPSCs affected the
      responses of the TC neurons. Contrary to our expectations, we found that
      prolonging IPSCs accelerates postinhibitory rebound (PIR) in TC neurons, and that
      increasing either the amplitude or duration of IPSCs desynchronizes PIR activity
      in a population of TC cells. Tonic injection of hyperpolarizing or depolarizing
      current dramatically alters the timing and synchrony of PIR. These results
      demonstrate that rhythmic PIR activity is an emergent property of interactions
      between intrinsic and synaptic currents, not just a passive reflection of
      incoming synaptic inhibition.

PMID- 16624946
TI  - Structure function and splice site analysis of the synaptogenic activity of the
      neurexin-1 beta LNS domain.
AB  - Recent findings suggest that the neurexin-neuroligin link promotes both GABAergic
      and glutamatergic synaptogenesis, but the mechanism by which neurexins influence
      the clustering of appropriate neuroligins and postsynaptic differentiation
      remains unclear. Previous studies suggested that the presence or absence of
      alternatively spliced residues at splice site 4 (S4) in the neurexin LNS domain
      may regulate neurexin function. We demonstrate that addition of the S4 insert
      selectively reduces the ability of neurexin-1beta to cluster neuroligin-1/3/4 and
      glutamatergic postsynaptic proteins, although clustering of neuroligin-2 and
      GABAergic postsynaptic proteins remain strong. Furthermore, addition of the S4
      insert decreases the binding affinity of neurexin-1beta to neuroligins-1 and -4
      but has little effect on binding to neuroligins-2 and -3. Additional structure
      function studies reveal the neurexin binding interface mediating synaptogenic
      activity to be composed primarily of residues in the beta2beta3, beta6beta7, and
      beta10beta11 loops on one rim of the LNS domain beta sandwich. Mutation of two
      predicted Ca(2+)-binding residues disrupts postsynaptic protein clustering and
      binding to neuroligins, consistent with previous findings that neurexin
      neuroligin binding is Ca2+ dependent. Glutamatergic postsynaptic clustering was
      more readily disrupted by the mutagenesis than GABAergic postsynaptic protein
      clustering. Perhaps neurexins-neuroligins, or neurexin-1beta at least, is most
      important for GABA synapse formation or controlling the balance of GABA and
      glutamate synapses. These results suggest that differential neurexin-neuroligin
      binding affinities and splice variations may play an instructive role in
      postsynaptic differentiation.

PMID- 16624947
TI  - A spin glass model of path integration in rat medial entorhinal cortex.
AB  - Electrophysiological recording studies in the dorsocaudal region of medial
      entorhinal cortex (dMEC) of the rat reveal cells whose spatial firing fields show
      a remarkably regular hexagonal grid pattern (Fyhn et al., 2004; Hafting et al.,
      2005). We describe a symmetric, locally connected neural network, or spin glass
      model, that spontaneously produces a hexagonal grid of activity bumps on a two
      dimensional sheet of units. The spatial firing fields of the simulated cells
      closely resemble those of dMEC cells. A collection of grids with different scales
      and/or orientations forms a basis set for encoding position. Simulations show
      that the animal's location can easily be determined from the population activity
      pattern. Introducing an asymmetry in the model allows the activity bumps to be
      shifted in any direction, at a rate proportional to velocity, to achieve path
      integration. Furthermore, information about the structure of the environment can
      be superimposed on the spatial position signal by modulation of the bump activity
      levels without significantly interfering with the hexagonal periodicity of firing
      fields. Our results support the conjecture of Hafting et al. (2005) that an
      attractor network in dMEC may be the source of path integration information
      afferent to hippocampus.

PMID- 16624948
TI  - Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the
      ubiquitin-proteasome system.
AB  - Increasing evidence links intraneuronal beta-amyloid (Abeta42) accumulation with
      the pathogenesis of Alzheimer's disease (AD). In Abeta precursor protein (APP)
      mutant transgenic mice and in human AD brain, progressive intraneuronal
      accumulation of Abeta42 occurs especially in multivesicular bodies (MVBs). We
      hypothesized that this impairs the MVB sorting pathway. We used the trafficking
      of the epidermal growth factor receptor (EGFR) and TrkB receptor to investigate
      the MVB sorting pathway in cultured neurons. We report that, during EGF
      stimulation, APP mutant neurons demonstrated impaired inactivation, degradation,
      and ubiquitination of EGFR. EGFR degradation is dependent on translocation from
      MVB outer to inner membranes, which is regulated by the ubiquitin-proteasome
      system (UPS). We provide evidence that Abeta accumulation in APP mutant neurons
      inhibits the activities of the proteasome and deubiquitinating enzymes. These
      data suggest a mechanism whereby Abeta accumulation in neurons impairs the MVB
      sorting pathway via the UPS in AD.

PMID- 16624949
TI  - Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB
      receptors in hippocampal pyramidal cells.
AB  - G-protein-coupled inwardly rectifying K+ channels (Kir3 channels) coupled to
      metabotropic GABAB receptors are essential for the control of neuronal
      excitation. To determine the distribution of Kir3 channels and their spatial
      relationship to GABAB receptors on hippocampal pyramidal cells, we used a high
      resolution immunocytochemical approach. Immunoreactivity for the Kir3.2 subunit
      was most abundant postsynaptically and localized to the extrasynaptic plasma
      membrane of dendritic shafts and spines of principal cells. Quantitative analysis
      of immunogold particles for Kir3.2 revealed an enrichment of the protein around
      putative glutamatergic synapses on dendritic spines, similar to that of GABA(B1).
      Consistent with this observation, a high degree of coclustering of Kir3.2 and
      GABA(B1) was revealed around excitatory synapses by the highly sensitive SDS
      digested freeze-fracture replica immunolabeling. In contrast, in dendritic shafts
      receptors and channels were found to be mainly segregated. These results suggest
      that Kir3.2-containing K+ channels on dendritic spines preferentially mediate the
      effect of GABA, whereas channels on dendritic shafts are likely to be activated
      by other neurotransmitters as well. Thus, Kir3 channels, localized to different
      subcellular compartments of hippocampal principal cells, appear to be
      differentially involved in synaptic integration in pyramidal cell dendrites.

PMID- 16624950
TI  - Windup in dorsal horn neurons is modulated by endogenous spinal mu-opioid
      mechanisms.
AB  - The mu-opioid receptor (MOR) plays a critical role in morphine analgesia and
      nociceptive transmission. However, the physiological roles for endogenous MOR
      mechanisms in modulating spinal nociceptive transmission, and particularly in the
      enhanced excitability of spinal nociceptive neurons after repeated noxious
      inputs, are less well understood. Using a MOR gene knock-out (-/-) approach and
      an MOR-preferring antagonist, we investigated the roles of endogenous MOR
      mechanisms in processing of acute noxious input and in neuronal sensitization
      during windup-inducing stimuli in wide dynamic range (WDR) neurons. Extracellular
      single-unit activity of WDR neurons was recorded in isoflurane-anesthetized MOR(
      /-) and wild-type C57BL/6 mice. There were no significant differences between the
      genotypes in the responses of deep WDR cells to acute mechanical stimuli, graded
      electrical stimuli, and noxious chemical stimuli applied to the receptive field.
      Intracutaneous electrical stimulation at 1.0 Hz produced similar levels of windup
      in both genotypes. In contrast, 0.2 Hz stimulation induced significantly higher
      levels of windup in MOR(-/-) mice compared with the wild-type group. In wild-type
      mice, spinal superfusion with naloxone hydrochloride (10 mM, 30 microl)
      significantly enhanced windup to 0.2 Hz stimulation in both deep and superficial
      WDR cells. A trend toward facilitation of windup was also observed during 1.0 Hz
      stimulation after naloxone treatment. These results suggest that endogenous MOR
      mechanisms are not essential in the processing of acute noxious mechanical and
      electrical stimuli by WDR neurons. However, MORs may play an important role in
      endogenous inhibitory mechanisms that regulate the development of spinal neuronal
      sensitization.

PMID- 16624951
TI  - Activated microglia contribute to the maintenance of chronic pain after spinal
      cord injury.
AB  - Traumatic spinal cord injury (SCI) results not only in motor impairment but also
      in chronic central pain, which can be refractory to conventional treatment
      approaches. It has been shown recently that in models of peripheral nerve injury,
      spinal cord microglia can become activated and contribute to development of pain.
      Considering their role in pain after peripheral injury, and because microglia are
      known to become activated after SCI, we tested the hypothesis that activated
      microglia contribute to chronic pain after SCI. In this study, adult male Sprague
      Dawley rats underwent T9 spinal cord contusion injury. Four weeks after injury,
      when lumbar dorsal horn multireceptive neurons became hyperresponsive and when
      behavioral nociceptive thresholds were decreased to both mechanical and thermal
      stimuli, intrathecal infusions of the microglial inhibitor minocycline were
      initiated. Electrophysiological experiments showed that minocycline rapidly
      attenuated hyperresponsiveness of lumbar dorsal horn neurons. Behavioral data
      showed that minocycline restored nociceptive thresholds, at which time spinal
      microglial cells assumed a quiescent morphological phenotype. Levels of
      phosphorylated-p38 were decreased in SCI animals receiving minocycline. Cessation
      of delivery of minocycline resulted in an immediate return of pain-related
      phenomena. These results suggest an important role for activated microglia in the
      maintenance of chronic central below-level pain after SCI and support the newly
      emerging role of non-neuronal immune cells as a contributing factor in post-SCI
      pain.

PMID- 16624952
TI  - Activation of group III metabotropic glutamate receptors attenuates rotenone
      toxicity on dopaminergic neurons through a microtubule-dependent mechanism.
AB  - Systemic administration of rotenone, a widely used pesticide, causes selective
      degeneration of nigral dopaminergic (DA) neurons and Parkinson's disease-like
      symptoms in animal models. Our previous study has shown that the microtubule
      depolymerizing activity of rotenone plays a critical role in its selective
      toxicity on tyrosine hydroxylase-positive (TH+) neurons in rat embryonic midbrain
      neuronal cultures. Here, we show that application of group III metabotropic
      glutamate receptor (mGluRIII) agonists (e.g., L-AP-4) significantly reduced
      rotenone toxicity on midbrain TH+ neurons in culture. The protective effect of L
      AP-4 was abolished by pharmacological inhibition of the microtubule-associated
      protein (MAP) kinase kinase (MEK) or overexpression of dominant-negative MEK1,
      suggesting its dependence on the MAP kinase cascade. We found that L-AP-4 induced
      a rapid and transient activation of the MAP kinase extracellular signal-regulated
      kinase (ERK) through a pathway mediated by dynamin, beta-arrestin 2, and Src. ERK
      activated in this manner targeted cytosolic rather than nuclear substrates.
      Consistent with this, L-AP-4 significantly attenuated rotenone- or colchicine
      induced microtubule depolymerization in an MEK-dependent manner. Moreover, L-AP-4
      decreased colchicine toxicity on TH+ neurons in an MEK-dependent manner as well.
      The protective effect of L-AP-4 against rotenone toxicity was occluded by the
      microtubule-stabilizing agent Taxol. Together, these results suggest that
      activation of group III metabotropic glutamate receptors attenuates the selective
      toxicity of rotenone on DA neurons by activating the MAP kinase pathway to
      stabilize microtubules. These findings may offer a novel neuroprotective approach
      against rotenone-induced parkinsonism.

PMID- 16624953
TI  - Mild hypoxia promotes survival and proliferation of SOD2-deficient astrocytes via
      c-Myc activation.
AB  - Mouse astrocytes deficient in the mitochondrial form of manganese superoxide
      dismutase (SOD2) do not survive in culture under atmospheric air with 20% oxygen
      (O2), which is a common condition for cell cultures. Seeding the cells and
      maintaining them under mild hypoxic conditions (5% O2) circumvents this problem
      and allows the cells to grow and become confluent. Previous studies from our
      laboratory showed that this adaptation of the cells was not attributable to
      compensation by other enzymes of the antioxidant defense system. We hypothesized
      that transcriptional activity and upregulation of genes other than those with an
      antioxidant function are involved. Our present study shows that c-Myc was
      significantly induced and that it inhibited p21 and induced proteins such as
      cyclin-dependent kinases, cyclin D, and cyclin E, which are involved in the cell
      cycle process, along with phosphorylation of the retinoblastoma protein and Cdc2
      (cell division cycle 2). These mechanisms contribute to cell proliferation. Small
      interfering RNA of c-Myc, however, blocked proliferation of SOD2 homozygous (SOD2
      /-) astrocytes under mild hypoxia consisting of 5% O2, whereas it did not affect
      the growth of wild-type astrocytes. Our results indicate that c-Myc plays a
      critical role in hypoxia-induced proliferation and survival of SOD2-/- astrocytes
      by overcoming injury caused by oxidative stress.

PMID- 16624954
TI  - Barrel map development relies on protein kinase A regulatory subunit II beta
      mediated cAMP signaling.
AB  - The cellular and molecular mechanisms mediating the activity-dependent
      development of brain circuitry are still incompletely understood. Here, we
      examine the role of cAMP-dependent protein kinase [protein kinase A (PKA)]
      signaling in cortical development and plasticity, focusing on its role in
      thalamocortical synapse and barrel map development. We provide direct evidence
      that PKA activity mediates barrel map formation using knock-out mice that lack
      type IIbeta regulatory subunits of PKA (PKARIIbeta). We show that PKARIIbeta
      mediated PKA function is required for proper dendritogenesis and the organization
      of cortical layer IV neurons into barrels, but not for the development and
      plasticity of thalamocortical afferent clustering into a barrel pattern. We
      localize PKARIIbeta function to postsynaptic processes in barrel cortex and show
      that postsynaptic PKA targets, but not presynaptic PKA targets, have decreased
      phosphorylation in pkar2b knock-out (PKARIIbeta(-/-)) mice. We also show that
      long-term potentiation at TC synapses and the associated developmental increase
      in AMPA receptor function at these synapses, which normally occurs as barrels
      form, is absent in PKARIIbeta(-/-) mice. Together, these experiments support an
      activity-dependent model for barrel map development in which the selective
      addition and elimination of thalamocortical synapses based on Hebbian mechanisms
      for synapse formation is mediated by a cAMP/PKA-dependent pathway that relies on
      PKARIIbeta function.

PMID- 16624955
TI  - Peripheral antinociceptive effects of exogenous and immune cell-derived
      endomorphins in prolonged inflammatory pain.
AB  - Endomorphins (EMs) are endogenous selective mu-opioid receptor agonists. Their
      role in inflammatory pain has not been fully elucidated. Here we examine
      peripheral antinociception elicited by exogenously applied EM-1 and EM-2 and the
      contribution of EM-containing leukocytes to stress- and corticotropin-releasing
      factor (CRF)-induced antinociception. To this end, we applied behavioral (paw
      pressure) testing, radioligand binding, immunohistochemistry, and flow cytometry
      in rats with unilateral hindpaw inflammation induced with Freund's adjuvant. EMs
      injected directly into both hindpaws produced antinociception exclusively in
      inflamed paws. This was blocked by locally applied mu-receptor-selective (D-Phe
      Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) but not kappa-receptor-selective (nor
      binaltorphimine) antagonists. Delta-receptor antagonists (naltrindole and N,N
      diallyl-Tyr-Aib-Aib-Phe-Leu) did not influence EM-1-induced but dose-dependently
      decreased EM-2-induced antinociception. Antibodies against beta-endorphin,
      methionine-enkephalin, or leucine-enkephalin did not significantly change EM-2
      induced antinociception. Both EMs displaced binding of [3H]-[D-Ala2,N-Me
      Phe4,Gly5-ol]enkephalin to mu-receptors in dorsal root ganglia (DRG). Using [3H]
      naltrindole or [(125)I]-[D-Pen2,5]-enkephalin, no detectable delta-binding was
      found in DRG of inflamed hindlimbs. Numerous beta-endorphin-containing and fewer
      EM-1- and EM-2-containing leukocytes were detected in subcutaneous tissue of
      inflamed paws. Leukocyte-depleting serum decreased the number of immigrating
      opioid-containing immune cells and attenuated swim stress- and CRF-induced
      antinociception in inflamed paws. Both forms of antinociception were strongly
      attenuated by anti-beta-endorphin and to a lesser degree by anti-EM-1 and anti-EM
      2 antibodies injected into inflamed paws. Together, exogenously applied and
      immune cell-derived EMs alleviate prolonged inflammatory pain through selective
      activation of peripheral opioid receptors. Exogenous EM-2 in addition to mu
      receptors also activates peripheral delta-receptors, which does not involve
      actions via other opioid peptides.

PMID- 16624956
TI  - Neural stem/progenitor cells participate in the regenerative response to
      perinatal hypoxia/ischemia.
AB  - Perinatal hypoxia/ischemia (H/I) is the leading cause of neurologic injury
      resulting from birth complications. Recent advances in critical care have
      dramatically improved the survival rate of infants suffering this insult, but
      approximately 50% of survivors will develop neurologic sequelae such as cerebral
      palsy, epilepsy or cognitive deficits. Here we demonstrate that tripotential
      neural stem/progenitor cells (NSPs) participate in the regenerative response to
      perinatal H/I as their numbers increase 100% by 3 d and that they alter their
      intrinsic properties to divide using expansive symmetrical cell divisions. We
      further show that production of new striatal neurons follows the expansion of
      NSPs. Increased proliferation within the NSP niche occurs at 2 d after perinatal
      H/I, and the proliferating cells express nestin. Of those stem-cell related genes
      that change, the membrane receptors Notch1, gp-130, and the epidermal growth
      factor receptor, as well as the downstream transcription factor Hes5, which
      stimulate NSP proliferation and regulate stem cellness are induced before NSP
      expansion. The mechanisms for the reactive expansion of the NSPs reported here
      reveal potential therapeutic targets that could be exploited to amplify this
      response, thus enabling endogenous precursors to restore a normal pattern of
      brain development after perinatal H/I.

PMID- 16624957
TI  - Neural basis for stereopsis from second-order contrast cues.
AB  - Humans and animals use visual cues such as brightness and color boundaries to
      identify objects and navigate through environments. However, even when these cues
      are not available, we can effortlessly perform these tasks by using second-order
      cues such as contrast variation (envelope) of patterns on surfaces. Previously,
      numerous psychophysical studies examined properties of binocular depth processing
      based on the contrast-envelope cues and suggested the existence of a stereo
      system that uses these cues. However, its physiological substrate has not been
      identified yet. Here, we show that a subset of cortical neurons in cat area 18
      show binocular interactions for the contrast-envelope stimuli. These neurons are
      capable of representing a variety of depths in the three-dimensional space based
      on the information available from contrast cues alone. Furthermore, these neurons
      show similar disparity-tuning curves for borders defined by both luminance and
      contrast cues. This cue-invariant tuning is consistent with a linear binocular
      convergence model for monocular luminance and contrast-envelope processing
      pathways.

PMID- 16624958
TI  - Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis
      and demyelination in twitcher.
AB  - Prostaglandin (PG) D2 is well known as a mediator of inflammation. Hematopoietic
      PGD synthase (HPGDS) is responsible for the production of PGD2 involved in
      inflammatory responses. Microglial activation and astrogliosis are commonly
      observed during neuroinflammation, including that which occurs during
      demyelination. Using the genetic demyelination mouse twitcher, a model of human
      Krabbe's disease, we discovered that activated microglia expressed HPGDS and
      activated astrocytes expressed the DP1 receptor for PGD2 in the brain of these
      mice. Cultured microglia actively produced PGD2 by the action of HPGDS. Cultured
      astrocytes expressed two types of PGD2 receptor, DP1 and DP2, and showed enhanced
      GFAP production after stimulation of either receptor with its respective agonist.
      These results suggest that PGD2 plays an important role in microglia/astrocyte
      interaction. We demonstrated that the blockade of the HPGDS/PGD2/DP signaling
      pathway using HPGDS- or DP1-null twitcher mice, and twitcher mice treated with an
      HPGDS inhibitor, HQL-79 (4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)
      propyl]piperidine), resulted in remarkable suppression of astrogliosis and
      demyelination, as well as a reduction in twitching and spasticity. Furthermore,
      we found that the degree of oligodendroglial apoptosis was also reduced in HPGDS
      null and HQL-79-treated twitcher mice. These results suggest that PGD2 is the key
      neuroinflammatory molecule that heightens the pathological response to
      demyelination in twitcher mice.

PMID- 16624959
TI  - Recurrent connection patterns of corticostriatal pyramidal cells in frontal
      cortex.
AB  - Corticostriatal pyramidal cells are heterogeneous in the frontal cortex. Here, we
      show that subpopulations of corticostriatal neurons in the rat frontal cortex are
      selectively connected with each other based on their subcortical targets. Using
      paired recordings of retrogradely labeled cells, we investigated the synaptic
      connectivity between two projection cell types: those projecting to the pons
      [corticopontine (CPn) cell], often with collaterals to the striatum, and those
      projecting to both sides of the striatum but not to the pons [crossed
      corticostriatal (CCS) cell]. The two types were morphologically differentiated in
      regard to their apical tufts. The dendritic morphologies of CCS cells were
      correlated with their somatic depth within the cortex. CCS cells had reciprocal
      synaptic connections with each other and also provided synaptic input to CPn
      cells. However, connections from CPn to CCS cells were rarely found, even in
      pairs showing CCS to CPn connectivity. Additionally, CCS cells preferentially
      innervated the basal dendrites of other CCS cells but made contacts onto both the
      basal and apical dendrites of CPn cells. The amplitude of synaptic responses was
      to some extent correlated with the contact site number. Ratios of the EPSC
      amplitude to the contact number tended to be larger in the CCS to CCS connection.
      Therefore, our data demonstrate that these two types of corticostriatal cells
      distinct in their dendritic morphologies show directional and domain-dependent
      preferences in their synaptic connectivity.

PMID- 16624960
TI  - Chondroitinase ABC digestion of the perineuronal net promotes functional
      collateral sprouting in the cuneate nucleus after cervical spinal cord injury.
AB  - Upregulation of extracellular chondroitin sulfate proteoglycans (CSPGs) after CNS
      injuries contributes to the impediment of functional recovery by restricting both
      axonal regeneration and synaptic plasticity. In the present study, the effect of
      degrading CSPGs with the application of the bacterial enzyme chondroitinase ABC
      (chABC) into the cuneate nucleus of rats partially denervated of forepaw dorsal
      column axons was examined. A dorsal column transection between the C6-C7 dorsal
      root entry zones was followed immediately by an ipsilateral brainstem injection
      of either chABC or a bacterial-derived control enzyme [penicillinase (P-ase)] and
      then subsequently (1 week later) followed with a second brainstem enzyme
      injection and cholera toxin B subunit (CTB) tracer injection into the ipsilateral
      forepaw digits and pads. After 1 additional week, the rats underwent
      electrophysiological receptive field mapping of the cuneate nucleus and/or
      anatomical evaluation. Examination of the brainstems of rats from each group
      revealed that CSPGs had been reduced after chABC treatment. Importantly, in the
      chABC-treated rats (but not in the P-ase controls), a significantly greater area
      of the cuneate nucleus was occupied by physiologically active CTB traced forepaw
      afferents that had been spared by the initial cord lesion. These results
      demonstrate, for the first time, a functional change directly linked to
      anatomical evidence of sprouting by spinal cord afferents after chABC treatment.

PMID- 16624961
TI  - Amygdala and ventromedial prefrontal cortex are inversely coupled during
      regulation of negative affect and predict the diurnal pattern of cortisol
      secretion among older adults.
AB  - Among younger adults, the ability to willfully regulate negative affect, enabling
      effective responses to stressful experiences, engages regions of prefrontal
      cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known
      to influence the hypothalamic-pituitary-adrenal axis, here we test whether PFC
      and amygdala responses during emotion regulation predict the diurnal pattern of
      salivary cortisol secretion. We also test whether PFC and amygdala regions are
      engaged during emotion regulation in older (62- to 64-year-old) rather than
      younger individuals. We measured brain activity using functional magnetic
      resonance imaging as participants regulated (increased or decreased) their
      affective responses or attended to negative picture stimuli. We also collected
      saliva samples for 1 week at home for cortisol assay. Consistent with previous
      work in younger samples, increasing negative affect resulted in ventral lateral,
      dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast
      to previous work, decreasing negative affect did not produce the predicted robust
      pattern of higher PFC and lower amygdala activation. Individuals demonstrating
      the predicted effect (decrease < attend in the amygdala), however, exhibited
      higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast.
      Furthermore, participants displaying higher VMPFC and lower amygdala signal when
      decreasing compared with the attention control condition evidenced steeper, more
      normative declines in cortisol over the course of the day. Individual differences
      yielded the predicted link between brain function while reducing negative affect
      in the laboratory and diurnal regulation of endocrine activity in the home
      environment.

PMID- 16624962
TI  - Noradrenergic activation amplifies bottom-up and top-down signal-to-noise ratios
      in sensory thalamus.
AB  - Thalamocortical cells receive sensory signals via primary sensory afferents and
      cortical signals via corticothalamic afferents. These signals are influenced by a
      variety of neuromodulators that are released in the thalamus during specific
      behavioral states. Hence, different neuromodulators may set different thalamic
      modes of sensory information processing. We found that noradrenergic activation
      affects sensory and corticothalamic signals in the whisker thalamus differently
      than cholinergic activation. Whereas cholinergic activation increases the
      spontaneous firing (noise) and enlarges the receptive fields of ventroposterior
      medial thalamus (VPM) cells, noradrenergic activation decreases spontaneous
      firing and focuses receptive fields. Consequently, for sensory signals,
      noradrenergic activation sets bottom-up thalamic processing to a focused and
      noise-free excitatory receptive field, which contrasts with the broad and noisy
      excitatory receptive field characteristic of cholinergic activation. For
      corticothalamic signals, noradrenergic activation sets top-down processing to a
      noise-free high-frequency signal detection mode, whereas cholinergic activation
      produces a noisy broadband signal detection mode. The effects of noradrenergic
      activation on signal-to-noise ratios of VPM cells were found to be mediated by
      nucleus reticularis thalamic (nRt) cells. Hence, a major role of nRt cells is to
      regulate the noise level of thalamocortical cells during sensory processing. In
      conclusion, different modulators establish distinct modes of bottom-up and top
      down information processing in the sensory thalamus.

PMID- 16624963
TI  - Isolating the modulatory effect of expectation on pain transmission: a functional
      magnetic resonance imaging study.
AB  - We use a novel balanced experimental design to specifically investigate brain
      mechanisms underlying the modulating effect of expected pain intensity on
      afferent nociceptive processing and pain perception. We used two visual cues,
      each conditioned to one of two noxious thermal stimuli [ approximately 48 degrees
      C (high) or 47 degrees C (low)]. The visual cues were presented just before and
      during application of the noxious thermal stimulus. Subjects reported
      significantly higher pain when the noxious stimulus was preceded by the high
      intensity visual cue. To control for expectancy effects, for one-half of the
      runs, the noxious thermal stimuli were accompanied by the cue conditioned to the
      other stimulus. Comparing functional magnetic resonance imaging blood oxygenation
      level-dependent activations produced by the high and low thermal stimulus
      intensities presented with the high-intensity visual cue showed significant
      activations in nociceptive regions of the thalamus, second somatosensory cortex,
      and insular cortex. To isolate the effect of expectancy, we compared activations
      produced by the two visual cues presented with the high-intensity noxious thermal
      stimulus; this showed significant differences in the ipsilateral caudal anterior
      cingulate cortex, the head of the caudate, cerebellum, and the contralateral
      nucleus cuneiformis (nCF). We propose that pain intensity expectancy modulates
      activations produced by noxious stimuli through a distinct modulatory network
      that converges with afferent nociceptive input in the nCF.

PMID- 16624964
TI  - Attentional modulation of thalamic reticular neurons.
AB  - The major pathway for visual information reaching cerebral cortex is through the
      lateral geniculate nucleus (LGN) of the thalamus. Acting on this vital relay is
      another thalamic nucleus, the thalamic reticular nucleus (TRN). This nucleus
      receives topographically organized collaterals from both thalamus and cortex and
      sends similarly organized projections back to thalamus. The inputs to the TRN are
      excitatory, but the output back to the thalamic relay is inhibitory, providing an
      ideal organization for modulating visual activity during early processing. This
      functional architecture led Crick in 1984 to hypothesize that TRN serves to
      direct a searchlight of attention to different regions of the topographic map;
      however, despite the substantial influence of this hypothesis, the activity of
      TRN neurons has never been determined during an attention task. We have
      determined the nature of the response of visual TRN neurons in awake monkeys, and
      the modulation of that response as the monkeys shifted attention between visual
      and auditory stimuli. Visual TRN neurons had a strong (194 spikes/s) and fast (25
      ms latency) transient increase of activity to spots of light falling in their
      receptive fields, as well as high background firing rate (45 spikes/s). When
      attention shifted to the spots of light, the amplitude of the transient visual
      response typically increased, whereas other neuronal response characteristics
      remained unchanged. Thus, as predicted previously, TRN activity is modified by
      shifts of visual attention, and these attentional changes could influence visual
      processing in LGN via the inhibitory connections back to the thalamus.

PMID- 16624965
TI  - Arsenic exposure from drinking water and risk of premalignant skin lesions in
      Bangladesh: baseline results from the Health Effects of Arsenic Longitudinal
      Study.
AB  - Millions of persons around the world are exposed to low doses of arsenic through
      drinking water. However, estimates of health effects associated with low-dose
      arsenic exposure have been extrapolated from high-dose studies. In Bangladesh,
      many persons have been exposed to a wide range of doses of arsenic from drinking
      water over a significant period of time. The authors evaluated dose-response
      relations between arsenic exposure from drinking water and premalignant skin
      lesions by using baseline data on 11,746 participants recruited in 2000-2002 for
      the Health Effects of Arsenic Longitudinal Study in Araihazar, Bangladesh.
      Several measures of arsenic exposure were estimated for each participant based on
      well-water arsenic concentration and usage pattern of the wells and on urinary
      arsenic concentration. In different regression models, consistent dose-response
      effects were observed for all arsenic exposure measures. Compared with drinking
      water containing <8.1 microg/liter of arsenic, drinking water containing 8.1
      40.0, 40.1-91.0, 91.1-175.0, and 175.1-864.0 microg/liter of arsenic was
      associated with adjusted prevalence odds ratios of skin lesions of 1.91 (95%
      confidence interval (CI): 1.26, 2.89), 3.03 (95% CI: 2.05, 4.50), 3.71 (95% CI:
      2.53, 5.44), and 5.39 (95% CI: 3.69, 7.86), respectively. The effect seemed to be
      influenced by gender, age, and body mass index. These findings provide
      information that should be considered in future research and policy decisions.

PMID- 16624966
TI  - Bayesian modeling of air pollution health effects with missing exposure data.
AB  - The authors propose a new statistical procedure that utilizes measurement error
      models to estimate missing exposure data in health effects assessment. The method
      detailed in this paper follows a Bayesian framework that allows estimation of
      various parameters of the model in the presence of missing covariates in an
      informative way. The authors apply this methodology to study the effect of
      household-level long-term air pollution exposures on lung function for subjects
      from the Southern California Children's Health Study pilot project, conducted in
      the year 2000. Specifically, they propose techniques to examine the long-term
      effects of nitrogen dioxide (NO2) exposure on children's lung function for
      persons living in 11 southern California communities. The effect of nitrogen
      dioxide exposure on various measures of lung function was examined, but, similar
      to many air pollution studies, no completely accurate measure of household-level
      long-term nitrogen dioxide exposure was available. Rather, community-level
      nitrogen dioxide was measured continuously over many years, but household-level
      nitrogen dioxide exposure was measured only during two 2-week periods, one period
      in the summer and one period in the winter. From these incomplete measures, long
      term nitrogen dioxide exposure and its effect on health must be inferred. Results
      show that the method improves estimates when compared with standard frequentist
      approaches.

PMID- 16624967
TI  - Variable selection for propensity score models.
AB  - Despite the growing popularity of propensity score (PS) methods in epidemiology,
      relatively little has been written in the epidemiologic literature about the
      problem of variable selection for PS models. The authors present the results of
      two simulation studies designed to help epidemiologists gain insight into the
      variable selection problem in a PS analysis. The simulation studies illustrate
      how the choice of variables that are included in a PS model can affect the bias,
      variance, and mean squared error of an estimated exposure effect. The results
      suggest that variables that are unrelated to the exposure but related to the
      outcome should always be included in a PS model. The inclusion of these variables
      will decrease the variance of an estimated exposure effect without increasing
      bias. In contrast, including variables that are related to the exposure but not
      to the outcome will increase the variance of the estimated exposure effect
      without decreasing bias. In very small studies, the inclusion of variables that
      are strongly related to the exposure but only weakly related to the outcome can
      be detrimental to an estimate in a mean squared error sense. The addition of
      these variables removes only a small amount of bias but can increase the variance
      of the estimated exposure effect. These simulation studies and other analytical
      results suggest that standard model-building tools designed to create good
      predictive models of the exposure will not always lead to optimal PS models,
      particularly in small studies.

PMID- 16624968
TI  - Declining vulnerability to temperature-related mortality in London over the 20th
      century.
AB  - The degree to which population vulnerability to outdoor temperature is reduced by
      improvements in infrastructure, technology, and general health has an important
      bearing on what realistically can be expected with future changes in climate.
      Using autoregressive Poisson models with adjustment for season, the authors
      analyzed weekly mortality in London, United Kingdom, during four periods (1900
      1910, 1927-1937, 1954-1964, and 1986-1996) to quantify changing vulnerability to
      seasonal and temperature-related mortality throughout the 20th century. Mortality
      patterns showed an epidemiologic transition over the century from high childhood
      mortality to low childhood mortality and towards a predominance of chronic
      disease mortality in later periods. The ratio of winter deaths to nonwinter
      deaths was 1.24 (95% confidence interval (CI): 1.16, 1.34) in 1900-1910, 1.54
      (95% CI: 1.42, 1.68) in 1927-1937, 1.48 (95% CI: 1.35, 1.64) in 1954-1964, and
      1.22 (95% CI: 1.13, 1.31) in 1986-1996. The temperature-mortality gradient for
      cold deaths diminished progressively: The increase in mortality per 1 degree C
      drop below 15 degrees C was 2.52% (95% CI: 2.00, 3.03), 2.34% (95% CI: 1.72,
      2.96), 1.64% (1.10, 2.19), and 1.17% (95% CI: 0.88, 1.45), respectively, in the
      four periods. Corresponding population attributable fractions were 12.5%, 11.2%,
      8.7%, and 5.4%. Heat deaths also diminished over the century. There was a
      progressive reduction in temperature-related deaths over the 20th century,
      despite an aging population. This trend is likely to reflect improvements in
      social, environmental, behavioral, and health-care factors and has implications
      for the assessment of future burdens of heat and cold mortality.

PMID- 16624969
TI  - Expression of p53 tumor suppressor protein in sun-exposed skin and associations
      with sunscreen use and time spent outdoors: a community-based study.
AB  - The p53 gene is a tumor suppressor gene that is commonly mutated in skin cancer
      and sun-exposed skin, and this can be detected through immunohistochemical
      expression of the p53 protein. The authors hypothesized that time spent outdoors
      is associated with p53 protein expression in human skin and that sunscreen use
      counteracts the association. In 1996, they investigated this in a community-based
      cross-sectional study in Australia. Detailed information about skin type, time
      spent outdoors, and sunscreen use was collected from 139 residents of a
      subtropical township who also provided a skin biopsy from the back of the hand
      for measurement of p53 expression. Increasing time spent outdoors was positively
      associated with immunoreactivity in the whole epidermis and in the basal layer of
      the epidermis. After adjustment for confounders, p53 immunoreactivity was twice
      as high for people who used sunscreen 1 or 2 days per week as for those who used
      sunscreen daily (whole epidermis: ratio estimate=2.0, 95% confidence interval:
      1.1, 3.6; basal layer: ratio estimate=1.7, 95% confidence interval: 0.9, 3.1).
      The authors conclude that p53 immunoreactivity in the skin is a marker of
      exposure to ultraviolet light in the past 6 months, but this may be mitigated by
      regular application of sunscreen.

PMID- 16624970
TI  - Methods for pooling results of epidemiologic studies: the Pooling Project of
      Prospective Studies of Diet and Cancer.
AB  - With the growing number of epidemiologic publications on the relation between
      dietary factors and cancer risk, pooled analyses that summarize results from
      multiple studies are becoming more common. Here, the authors describe the methods
      being used to summarize data on diet-cancer associations within the ongoing
      Pooling Project of Prospective Studies of Diet and Cancer, begun in 1991. In the
      Pooling Project, the primary data from prospective cohort studies meeting
      prespecified inclusion criteria are analyzed using standardized criteria for
      modeling of exposure, confounding, and outcome variables. In addition to
      evaluating main exposure-disease associations, analyses are also conducted to
      evaluate whether exposure-disease associations are modified by other dietary and
      nondietary factors or vary among population subgroups or particular cancer
      subtypes. Study-specific relative risks are calculated using the Cox proportional
      hazards model and then pooled using a random- or mixed-effects model. The study
      specific estimates are weighted by the inverse of their variances in forming
      summary estimates. Most of the methods used in the Pooling Project may be adapted
      for examining associations with dietary and nondietary factors in pooled analyses
      of case-control studies or case-control and cohort studies combined.

PMID- 16624971
TI  - Immunomodulatory therapeutic effect of glatiramer acetate on several murine
      models of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is characterized by detrimental immune
      reactivity in the gut and imbalance between proinflammatory and anti-inflammatory
      reactivity. In an attempt to down-regulate colitis, we investigated the effect of
      the immunomodulator glatiramer acetate (GA, Copaxone, copolymer 1) on two murine
      models of IBD, chemically induced and spontaneous. Acute experimental colitis of
      different levels of severity was induced in C57BL/6 mice by dextran sulfate
      sodium (DSS) administered orally at different concentrations and frequencies. It
      was manifested in weight loss, intestinal bleeding, and diarrhea, as well as by
      macroscopic and microscopic colon damage. GA treatment led to amelioration of all
      of these pathological manifestations, resulting in improved long-term survival.
      Moreover, even when colitis was induced by three cycles of DSS in this highly
      susceptible mouse strain, as well as in BALB/c mice that exhibit a chronic
      disease pattern, a substantial reduction in disease activity and mortality was
      obtained. GA treatment induced a beneficial effect also in a spontaneous model of
      colitis developed in the C3H/HeJBir IL-10-deficient mice. The detrimental
      proinflammatory response manifested by proliferation, tumor necrosis factor
      alpha, and interferon-gamma expression was modulated by GA, whereas the
      regulatory anti-inflammatory transforming growth factor-beta and IL-10 cytokines
      response was elevated. This was demonstrated on the level of protein secretion in
      splenocytes and local mesenteric lymphocytes in response to syngeneic colon
      extract and in the overall response to anti-CD3, as well as on the level of mRNA
      expression in the colon.

PMID- 16624972
TI  - Role of phosphatidylinositol 3-kinase/AKT as a survival pathway against CYP2E1
      dependent toxicity.
AB  - The objective of this work was to evaluate the possible role of PI3-kinase/AKT as
      a survival pathway against CYP2E1-dependent toxicity. E47 cells (HepG2 cells
      transfected with human CYP2E1 cDNA) exposed to 25 microM iron-nitrilotriacetate+5
      microM arachidonic acid (AA+Fe) developed higher toxicity than C34 cells (HepG2
      cells transfected with empty plasmid). Toxicity was associated with increased
      oxidative stress and activation of calcium-dependent hydrolases calpain and
      phospholipase A2. Treatment of E47, but not C34 cells, with arachidonic acid and
      iron (AA+Fe) led to a decrease in the phosphorylation state of AKT. 2-(4
      Morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), a specific
      inhibitor of PI3-kinase, produced a further decrease of phosphorylated AKT in
      AA+Fe-treated E47 cells. LY294002 and down-regulation of endogenous AKT with
      small interference RNAs increased the toxicity of AA+Fe in E47 cells. Toxicity of
      AA+Fe in rat hepatocytes was also increased by LY294002. LY294002 did not affect
      phospholipase A2 or calpain activation, CYP2E1 activity, or lipid peroxidation
      elicited by AA+Fe. alpha-Tocopherol prevented both AA+Fe and AA+Fe+LY294002
      induced toxicity and decrease of phosphorylated AKT. LY294002 potentiated AA+Fe
      induced loss of mitochondrial membrane potential and ATP, whereas overexpression
      of constitutively active AKT partially prevented mitochondrial impairment and
      toxicity. Mitochondrial permeability transition inhibitors prevented both AA+Fe
      and AA+Fe+LY294002-induced toxicity and decrease of mitochondrial membrane
      potential. These results suggest that: i) AA+Fe+CYP2E1-induced oxidative stress
      decreases AKT activation; ii) AKT inactivation induces mitochondrial impairment
      associated with opening of the permeability transition pore but is not dependent
      on the activation state of bad, glycogen synthase kinase-3beta, mammalian target
      of rapamycin, or bcl-xL; and iii) PI3-kinase/AKT may serve as a survival pathway
      against CYP2E1-dependent toxicity.

PMID- 16624973
TI  - Nuclear factor-kappa B-independent anti-inflammatory action of salicylate in
      human endothelial cells: induction of heme oxygenase-1 by the c-jun N-terminal
      kinase/activator protein-1 pathway.
AB  - In contrast to aspirin, salicylate, its active metabolite, possesses profound
      anti-inflammatory properties without blocking cyclooxygenase. Inhibition of the
      transcription factor nuclear factor-kappaB (NF-kappaB) has been discussed to play
      a role in the anti-inflammatory profile of salicylate. However, NF-kappaB
      independent effects of salicylate have been assumed but have up to now been
      poorly investigated. Therefore, the aim of the present study was to investigate
      NF-kappaB-independent anti-inflammatory mechanisms of salicylate in human
      umbilical vein endothelial cells using interleukin-4 (IL-4) as NF-kappaB
      independent proinflammatory stimulus and P-selectin as inflammatory read-out
      parameter. Using quantitative real-time reverse transcription-polymerase chain
      reaction, we found that salicylate decreases IL-4-induced P-selectin expression.
      As judged by Western blot analysis, salicylate increased endothelial heme
      oxygenase-1 (HO-1) protein levels. Using both the HO-1 inhibitor tin(II)
      protoporphyrin IX and HO-1 antisense oligonucleotides, we causally linked the
      induction of HO-1 to the decrease of P-selectin. Moreover, we were interested in
      the signaling mechanisms leading to the up-regulation of HO-1 by salicylate. c
      Jun NH2-terminal kinase (JNK) was found to be activated by salicylate, and we
      could causally link this activation to the induction of HO-1 by using the JNK
      inhibitor 1,9-pyrazoloanthrone. By applying activator protein-1 (AP-1) decoys, it
      was shown that the transcription factor AP-1 is crucially involved in the up
      regulation of HO-1 downstream of JNK. In summary, our study introduces HO-1 as
      novel NF-kappaB-independent anti-inflammatory target of salicylate in human
      endothelial cells. Moreover, we elucidated the JNK/AP-1 pathway as crucial for
      the induction of HO-1 by salicylate.

PMID- 16624974
TI  - Research findings evince benefits of nursing theory-guided practice.

PMID- 16624975
TI  - The possibility of changing meaning in light of space and place.
AB  - The author considers the possibility of changing meaning in light of space and
      place. Many questions are raised, including a fundamental question: If we simply
      choose the meaning of space and place based on personal knowing, regardless of
      the space and place we are in, does space and place really matter with regard to
      the possibility of changing meaning? Many possibilities of changing meaning in
      light of space and place are explored, including the influence of personal
      knowing, new life experiences and understandings, changes to space and place,
      unique languaging in space and place, imaging space and place, and engaging in
      the wonder and mystery of space and place beyond this realm. The possibility of
      changing meaning is significant in that new meanings open doors to different
      choices-and living choices is living health.

PMID- 16624977
TI  - Finding research in cyberspace.

PMID- 16624978
TI  - Fables: ways of knowing and understanding meaning in nursing.
AB  - Fables are literary short stories intended to convey a moral maxim for some
      aspect of human living. Within the discipline of nursing, a fable is a medium by
      which stories and themes of humanly lived phenomena may be viewed in light of a
      particular philosophical lens of understanding. The fable offers possibilities
      for instruction through illuminating fictitious characters and offering notions
      for what a member of a discipline ought to do. In this article, the author shall
      present a fable and offer an interpretation from a human becoming perspective for
      what one ought to do in the discipline of nursing.

PMID- 16624979
TI  - What stories and fables can teach us.
AB  - This column describes the influence of narrative on individuals and societies.
      More importantly, it describes the importance of story in dealing with health and
      quality of life issues. The idea of story as an epistemology is discussed.
      Individual stories which were created in seminars on writing for publication are
      presented along with stories and fables that lend further understanding to lived
      experiences of health. Ideas for teaching-learning in nursing regarding the
      issues in the stories are presented. Parse's human becoming theory is used to
      further explicate understanding of these ideas.

PMID- 16624980
TI  - Human becoming practice around the globe: exploring the art of living true
      presence.
AB  - In this column, the human becoming practice methodology is illuminated and some
      of the questions that people have asked about living the art of human becoming
      are presented. The human becoming teaching-learning processes are discussed as a
      way of coming to know what it takes to live true presence, and the role of
      stories in teaching-learning human becoming practice is explored. Previously
      published human becoming practice stories are presented as an answer to many of
      the questions that persons have asked about human becoming-guided practice.

PMID- 16624981
TI  - Challenging the atheoretical production of nursing knowledge: a response to Reed
      and Rolfe's column.
AB  - This column is a response to Reed and Rolfe's column in the January 2006 issue of
      Nursing Science Quarterly. The authors present their views about Reed and Rolfe's
      ideas by focusing their discussion and questions on three main topics: the impact
      of nurses' conceptual thinking, values, and culture on their perspectives and
      experiences; the reality that nursing theory-guided practice is already a
      meaningful reality in nursing; and the belief that in order not to limit
      knowledge development, science must be viewed as more than a study of proximal
      causes.

PMID- 16624982
TI  - A unitary healing praxis model for women in despair.
AB  - The evolution of a unitary healing praxis model derived from three unitary
      appreciative inquiries of despair is described. Explication of unitary
      appreciative inquiry and how it informed and contributed to the development of
      the model is provided. The model is based on a conceptualization of healing as
      appreciating the inherent wholeness of life and provides knowledge specific to
      the individual lives of women in despair. The process of generative theorizing
      that led to the creation of the model is explicated. Unitary, appreciative, and
      participatory responses to despair are integrated in the model, praxis modalities
      are delineated, key concerns and perspectives of women in despair are addressed,
      and potentialities for healing are illustrated.

PMID- 16624983
TI  - The lived experience of sacrificing something important.
AB  - The purposes of this research, using the Parse method, were to discover the
      structure of sacrificing something important and to expand the theory of human
      becoming. The core concepts of relinquishing the cherished, shifting preferred
      options, and fortifying affiliations were discovered during the process of
      extraction-synthesis using synopses of dialogues from 10 church parishioners. The
      structure, sacrificing something important is relinquishing the cherished while
      shifting preferred options amid fortifying affiliations is the central finding of
      this study, adding to the theory of human becoming, stimulating further research,
      and informing nurses about this universal lived experience of health.

PMID- 16624984
TI  - Human becoming criticism--a critique of Florczak's study on the lived experience
      of sacrificing something important.
AB  - This article presents a critical appraisal of Kristine Florczak's Parse research
      method study on the phenomenon of sacrificing something important. The processes
      of Mitchell's framework for human becoming criticism-sketching the horizon of
      understanding, illuminating artistic disclosure, and enhancing the original with
      artform-are utilized.

PMID- 16624985
TI  - Self-care operations and nursing interventions for children with cancer and their
      parents.
AB  - As individuals assume more responsibility for their healthcare, nurses need to
      explore methods to support families' self-care practices. The purpose of this
      qualitative study was to: (a) determine what self-care and dependent-care
      operations children and parents perform to address self-care requisites, and (b)
      explore nursing interventions to promote operations. Orem's theory of self-care,
      theory of self-care deficit, and theory of nursing system were employed. Twenty
      seven participants were interviewed about their cancer experiences. Results were
      that children and parents performed estimative, transitional, and productive
      operations to meet self-care requisites. Various nursing interventions that
      promoted these operations were identified. Recommendations were made for further
      interventions to support families.

PMID- 16624986
TI  - Nursing issues in Hong Kong.
AB  - Changes in nursing in Hong Kong over the past decade have had more to do with the
      changes in the world and the region's economy and population than the changes
      instituted by the Republic of China. Hong Kong's nearly 7 million people's health
      is, like in other places, threatened by a shortage of skilled and experienced
      nurses. Hong Kong's three major university-based nursing programs, if they can
      work together creatively, have the potential to avert a decline in quality of
      healthcare in Hong Kong and advance nursing at the same time.

PMID- 16624987
TI  - Nursing in Hong Kong: issues and challenges.
AB  - This column provides a discussion of the issues and challenges facing nurses and
      nursing in Hong Kong. The author introduces the role of nurses in the special
      administrative region and focuses on workforce, educational and practice issues,
      as well as on leadership in nursing. He concludes that Hong Kong needs to have a
      strategic plan to determine sufficient numbers of properly educated nurses.

PMID- 16624988
TI  - The meaning of being supportive for family caregivers as narrated by registered
      nurses working in palliative homecare.
AB  - The aim of this study was to illuminate the meaning of being supportive to family
      caregivers who care for a relative at home as narrated by registered nurses. The
      context used to allow for the meaning of being supportive to be illuminated was
      palliative home care. The study uses a phenomenological-hermeneutical method
      inspired by the philosophy of Ricoeur. Data consisted of narrative interviews,
      which were analyzed in three recurring phases: naive reading, structural analyses
      and interpreted whole. Twenty nurses from the hospitals in Sweden participated in
      the study. Two core themes were found: forming a relationship and keeping
      caregiving at home.

PMID- 16624989
TI  - A role for mitochondrial aquaporins in cellular life-and-death decisions?
AB  - Mitochondria dominate the process of life-and-death decisions of the cell.
      Continuous generation of ATP is essential for cell sustenance, but, on the other
      hand, mitochondria play a central role in the orchestra of events that lead to
      apoptotic cell death. Changes of mitochondrial volume contribute to the
      modulation of physiological mitochondrial function, and several ion permeability
      pathways located in the inner mitochondrial membrane have been implicated in the
      mediation of physiological swelling-contraction reactions, such as the K+ cycle.
      However, the channels and transporters involved in these processes have not yet
      been identified. Osmotic swelling is also one of the fundamental characteristics
      exhibited by mitochondria in pathological situations, which activates downstream
      cascades, culminating in apoptosis. The permeability transition pore has long
      been postulated to be the primary mediator for water movement in mitochondrial
      swelling during cell death, but its molecular identity remains obscure.
      Inevitably, accumulating evidence shows that mitochondrial swelling induced by
      apoptotic stimuli can also occur independently of permeability transition pore
      activation. Recently, a novel mechanism for osmotic swelling of mitochondria has
      been described. Aquaporin-8 and -9 channels have been identified in the inner
      mitochondrial membrane of various tissues, including the kidney, liver, and
      brain, where they may mediate water transport associated with physiological
      volume changes, contribute to the transport of metabolic substrates, and/or
      participate in osmotic swelling induced by apoptotic stimuli. Hence, the recent
      discovery that aquaporins are expressed in mitochondria opens up new areas of
      investigation in health and disease.

PMID- 16624990
TI  - K+ channel KV3.1 associates with OSP/claudin-11 and regulates oligodendrocyte
      development.
AB  - K(+) channels are differentially expressed throughout oligodendrocyte (Olg)
      development. K(V)1 family voltage-sensitive K(+) channels have been implicated in
      proliferation and migration of Olg progenitor cell (OPC) stage, and inward
      rectifier K+ channels (K(IR))4.1 are required for OPC differentiation to myelin
      forming Olg. In this report we have identified a Shaw family K(+) channel,
      K(V)3.1, that is involved in proliferation and migration of OPC and axon
      myelination. Application of anti-K(V)3.1 antibody or knockout of Kv3.1 gene
      decreased the sustained K(+) current component of OPC by 50% and 75%,
      respectively. In functional assays block of K(V)3.1-specific currents or knockout
      of Kv3.1 gene inhibited proliferation and migration of OPC. Adult Kv3.1 gene
      knockout mice had decreased diameter of axons and decreased thickness of myelin
      in optic nerves compared with age-matched wild-type littermates. Additionally,
      K(V)3.1 was identified as an associated protein of Olg-specific protein
      (OSP)/claudin-11 via yeast two-hybrid analysis, which was confirmed by
      coimmunoprecipitation and coimmunohistochemistry. In summary, the K(V)3.1 K(+)
      current accounts for a significant component of the total K(+) current in cells
      of the Olg lineage and, in association with OSP/claudin-11, plays a significant
      role in OPC proliferation and migration and myelination of axons.

PMID- 16624991
TI  - Evidence from knockout mice against physiologically significant aquaporin 8
      facilitated ammonia transport.
AB  - Aquaporin (AQP)8-facilitated transport of NH(3) has been suggested recently by
      increased NH(3) permeability in Xenopus oocytes and yeast expressing human or rat
      AQP8. We tested the proposed roles of AQP8-facilitated NH(3) transport in
      mammalian physiology by comparative phenotype studies in wild-type vs. AQP8-null
      mice. AQP8-facilitated NH(3) transport was confirmed in mammalian cell cultures
      expressing rat or mouse AQP8, in which the fluorescence of a pH-sensing yellow
      fluorescent protein was measured in response to ammonia (NH(3)/NH(4)(+))
      gradients. Relative AQP8 single-channel NH(3)-to-water permeability was
      approximately 0.03. AQP8-facilitated NH(3) and water permeability in a native
      tissue was confirmed in membrane vesicles isolated from testes of wild-type vs.
      AQP8-null mice, in which BCECF was used as an intravesicular pH indicator. A
      series of in vivo studies were done in mice, including 1) serum ammonia
      measurements before and after ammonia infusion, 2) renal ammonia clearance, 3)
      colonic ammonia absorption, and 4) liver ammonia accumulation and renal ammonia
      excretion after acute and chronic ammonia loading. Except for a small reduction
      in hepatic ammonia accumulation and increase in ammonia excretion in AQP8-null
      mice loaded with large amounts of ammonia, there were no significant differences
      in wild-type vs. AQP8-null mice. Our results support the conclusion that AQP8 can
      facilitate NH(3) transport but provide evidence against physiologically
      significant AQP8-facilitated NH(3) transport in mice.

PMID- 16624992
TI  - Beta-subunit of cardiac Na+-K+-ATPase dictates the concentration of the
      functional enzyme in caveolae.
AB  - Previous studies showed the presence of a significant fraction of Na(+)-K(+)
      ATPase alpha-subunits in cardiac myocyte caveolae, suggesting the caveolar
      interactions of Na(+)-K(+)-ATPase with its signaling partners. Because both alpha
      and beta-subunits are required for ATPase activity, to clarify the status of the
      pumping function of caveolar Na(+)-K(+)-ATPase, we have examined the relative
      distribution of two major subunit isoforms (alpha(1) and beta(1)) in caveolar and
      noncaveolar membranes of adult rat cardiac myocytes. When cell lysates treated
      with high salt (Na(2)CO(3) or KCl) concentrations were fractionated by a standard
      density gradient procedure, the resulting light caveolar membranes contained 30
      40% of alpha(1)-subunits and 80-90% of beta(1)-subunits. Use of Na(2)CO(3) was
      shown to inactivate Na(+)-K(+)-ATPase; however, caveolar membranes obtained by
      the KCl procedure were not denatured and contained approximately 75% of total
      myocyte Na(+)-K(+)-ATPase activity. Sealed isolated caveolae exhibited active
      Na(+) transport. Confocal microscopy supported the presence of alpha,beta
      subunits in caveolae, and immunoprecipitation showed the association of the
      subunits with caveolin oligomers. The findings indicate that cardiac caveolar
      inpocketings are the primary portals for active Na(+)-K(+) fluxes, and the sites
      where the pumping and signaling functions of Na(+)-K(+)-ATPase are integrated.
      Preferential concentration of beta(1)-subunit in caveolae was cell specific; it
      was also noted in neonatal cardiac myocytes but not in fibroblasts and A7r5
      cells. Uneven distributions of alpha(1) and beta(1) in early and late endosomes
      of myocytes suggested different internalization routes of two subunits as a
      source of selective localization of active Na(+)-K(+)-ATPase in cardiac caveolae.

PMID- 16624994
TI  - Neural representation of information measure in the primate premotor cortex.
AB  - Animals seek information to reduce their efforts to receive rewards and perform
      actions that enable them to gain more information. The ability of seeking
      information subserves higher cognition processes such as planning and reasoning.
      There exists limited information on how the brain measures and seeks information.
      In this study, I discuss results indicating that the brain quantifies information
      by using the information-theoretic measure. The monkeys were trained to perform
      saccadic eye movement to one of the visual targets. When required to choose from
      the targets that included varying amounts of information regarding the goal, the
      animals selected the most informative target. While making a choice, the neurons
      in the dorsal premotor cortex exhibited activity that reflected the corresponding
      information value. The population response of these neurons was examined using
      the following three measures: the information-theoretic measure, probability
      gain, and absolute change in beliefs. Changes in this response exhibited
      relatively similar proportionality to the three measures. An analysis of two
      intuitive conditions for information measures, decreasing monotonicity on
      probability and additivity between independent events, showed that only the
      information-theoretic measure satisfies both the conditions. These results
      suggest that in comparison with the other measures, the information-theoretic
      measure is more plausible for information measure in the brain.

PMID- 16624993
TI  - Ethanol potentiates GABAergic synaptic transmission in a postsynaptic
      neuron/synaptic bouton preparation from basolateral amygdala.
AB  - Interactions between ethanol and synaptic transmission mediated by gamma -amino-N
      butyric acid (GABA) have been suggested to contribute to alcohol intoxication.
      Ethanol effects on postsynaptic GABAA receptors have been the major focus of this
      line of research. There is increasing evidence that ethanol potentiation of
      GABAergic transmission involves increased GABA release from presynaptic
      terminals. In the present study, a mechanically isolated neuron/bouton
      preparation from the basolateral amygdala was used to examine the effects of
      ethanol on spontaneous GABAergic synaptic currents elicited by GABA release from
      the presynaptic terminals. We found that ethanol application produced a rapid
      increase in the frequency of spontaneous GABAergic synaptic currents. An acute
      tolerance to ethanol was also observed, and this tolerance involved GABAB
      receptor activation. The ethanol-induced potentiation did not involve alterations
      in the function of postsynaptic GABAA receptors and was independent of
      presynaptic action potential firing. These findings indicate that ethanol
      potentiates GABA release, most likely via a direct action on presynaptic boutons.

PMID- 16624995
TI  - GABAergic protection of hippocampal pyramidal neurons against glutamate insult:
      deficit in young animals compared to adults.
AB  - Hypoxia-ischemia (HI) injury in neonatal animals leads to selective regional loss
      of neurons including CA1 and CA3 pyramidal neurons of the hippocampus as well as
      nonlethal pathologies. Glutamate-receptor over-activation and Ca2+ influx are
      involved in these neonatal changes. We examined glutamate-evoked Ca2+ responses
      in neonatal (PN 7-13) and young adult (PN 21-27) CA1 pyramidal neurons in acute
      slices from rats. In neonates, transient exposure to glutamate produced large
      Ca2+ increases throughout neurons, including distal dendrites (primary Ca2+
      responses). Repeated exposures resulted in sustained Ca2+ increases in apical
      dendrites (secondary Ca2+ responses) that were independent of continued glutamate
      exposure. These responses propagated and invaded the soma, resulting in
      irrecoverably high Ca2+ elevations. In neurons from adults, identical glutamate
      exposure evoked primary Ca2+ responses only in somata and proximal apical
      dendrites. Repeated glutamate exposures in the adult neurons also led to
      secondary Ca2+ responses, but they arose in the peri-somatic region and then
      spread outward to distal apical dendrites, again without recovery. More stimuli
      were required to initiate secondary responses in neurons from adult versus
      neonates. Block of GABAA receptors in adults caused the primary and secondary
      responses to revert to the spatial pattern seen in the neonates and greatly
      increased their vulnerability to glutamate. These findings suggest that
      neurodegenerative secondary Ca2+ events may be important determinants of
      susceptibility to HI injury in the developing CNS and that immature CA1 neurons
      may be more susceptible to excitotoxic injury due at least in part to
      insufficient development of GABAergic inputs to their dendrites.

PMID- 16624996
TI  - Time course of oculomotor inhibition revealed by saccade trajectory modulation.
AB  - Selecting a stimulus as the target for a goal-directed movement involves
      inhibiting other competing possible responses. Both target and distractor stimuli
      activate populations of neurons in topographic oculomotor maps such as the
      superior colliculus. Local inhibitory interconnections between these populations
      ensure only one saccade target is selected. Suppressing saccades to distractors
      may additionally involve inhibiting corresponding map regions to bias the local
      competition. Behavioral evidence of these inhibitory processes comes from the
      effects of distractors on oculomotor and manual trajectories. Individual saccades
      may initially deviate either toward or away from a distractor, but the source of
      this variability has not been investigated. Here we investigate the relation
      between distractor-related deviation of trajectory and saccade latency. Targets
      were presented with, or without, distractors, and the deviation of saccade
      trajectories arising from the presence of distractors was measured. A fixation
      gap paradigm was used to manipulate latency independently of the influence of
      competing distractors. Shorter-latency saccades deviated toward distractors and
      longer-latency saccades deviated away from distractors. The transition between
      deviation toward or away from distractors occurred at a saccade latency of around
      200 ms. This shows that the time course of the inhibitory process involved in
      distractor related suppression is relatively slow.

PMID- 16624997
TI  - Two opposing roles of 4-AP-sensitive K+ current in initiation and invasion of
      spikes in rat mesencephalic trigeminal neurons.
AB  - The axon initial segment plays important roles in spike initiation and invasion
      of axonal spikes into the soma. Among primary sensory neurons, those in the
      mesencephalic trigeminal nucleus (MTN) are exceptional in their ability to
      initiate soma spikes (S-spikes) in response to synaptic inputs, consequently
      displaying two kinds of S-spikes, one caused by invasion of an axonal spike
      arising from the sensory receptor and the other initiated by somatic inputs. We
      investigated where spikes are initiated in such MTN neurons and whether there are
      any differences between the two kinds of S-spikes. Simultaneous patch-clamp
      recordings from the soma and axon hillock revealed a spike-backpropagation from
      the spike-initiation site in the stem axon to the soma in response to 1-ms
      somatic current pulse, which disclosed the delayed emergence of S-spikes after
      the current-pulse offset. These initiated S-spikes were smaller in amplitude than
      S-spikes generated by stimulation of the stem axon; however, 4-AP (< or =0.5 mM)
      eliminated the amplitude difference. Furthermore, 4-AP dramatically shortened the
      delay in spike initiation without affecting the spike-backpropagation time in the
      stem axon, whereas it substantially prolonged the refractory period of S-spikes
      arising from axonal-spike invasion without significantly affecting that of
      presumed axonal spikes. These observations suggest that 4-AP-sensitive K(+)
      currents exert two opposing effects on S-spikes depending on their origins:
      suppression of spike initiation and facilitation of axonal-spike invasion at
      higher frequencies. Consistent with these findings, strong immunoreactivities for
      Kv1.1 and Kv1.6, among 4-AP-sensitive and low-voltage-activated Kv1 family
      examined, were detected in the soma but not in the stem axon of MTN neurons.

PMID- 16624998
TI  - Efficient estimation of detailed single-neuron models.
AB  - Biophysically accurate multicompartmental models of individual neurons have
      significantly advanced our understanding of the input-output function of single
      cells. These models depend on a large number of parameters that are difficult to
      estimate. In practice, they are often hand-tuned to match measured physiological
      behaviors, thus raising questions of identifiability and interpretability. We
      propose a statistical approach to the automatic estimation of various
      biologically relevant parameters, including 1) the distribution of channel
      densities, 2) the spatiotemporal pattern of synaptic input, and 3) axial
      resistances across extended dendrites. Recent experimental advances, notably in
      voltage-sensitive imaging, motivate us to assume access to: i) the spatiotemporal
      voltage signal in the dendrite and ii) an approximate description of the channel
      kinetics of interest. We show here that, given i and ii, parameters 1-3 can be
      inferred simultaneously by nonnegative linear regression; that this optimization
      problem possesses a unique solution and is guaranteed to converge despite the
      large number of parameters and their complex nonlinear interaction; and that
      standard optimization algorithms efficiently reach this optimum with modest
      computational and data requirements. We demonstrate that the method leads to
      accurate estimations on a wide variety of challenging model data sets that
      include up to about 10(4) parameters (roughly two orders of magnitude more than
      previously feasible) and describe how the method gives insights into the
      functional interaction of groups of channels.

PMID- 16624999
TI  - Stimulation of the human frontal eye fields modulates sensitivity of extrastriate
      visual cortex.
AB  - The precise role of frontal eye fields (FEF) in vision independent of their role
      in eye movements remains a matter of debate. One proposal is that the FEF exert
      top-down influences on the extrastriate visual cortex prior to eye movement
      preparation. Here we establish, by use of transcranial magnetic stimulation
      (TMS), that activity in the human FEFs has a direct effect on the sensitivity of
      extrastriate visual area MT/V5, and that the spatial organization of this top
      down effect is lateralized in the human brain. We show that phosphene threshold
      the TMS intensity required to elicit a visual perception-for MT/V5 stimulation
      changes as a function of the delay between the application of TMS over FEF and
      MT/V5. The effects were specific to the location and time of stimulation.
      Stimulation of FEF 20-40 ms prior to stimulation of MT/V5 decreased the intensity
      of MT/V5 stimulation required to elicit phosphenes: TMS of the right FEF changed
      the sensitivity of left and right MT/V5 whereas TMS of the left FEF changed the
      sensitivity only of the left MT/V5. Thus, the sensitivity of human extrastriate
      cortex is modulated by activity in the FEF.

PMID- 16625000
TI  - Comparison among some models of orientation selectivity.
AB  - Several models exist for explaining primary visual cortex (V1) orientation
      tuning. The modified feedforward model (MFM) and the recurrent model (RM) are
      major examples. We have implemented these two models, at the same level of
      detail, alongside a few newer variations, and thoroughly compared their receptive
      field structures. We found that antiphase inhibition in the MFM enhances both
      spatial phase information and orientation tuning, producing well-tuned simple
      cells. This remains true for a newer version of the MFM that incorporates untuned
      complex-cell inhibition. In contrast, when the recurrent connections in the RM
      are strong enough to produce typical V1 orientation tuning, they also eliminate
      spatial phase information, making the cells complex. Introducing phase
      specificity into the connections of the RM (as done in an original version of the
      RM) can make the cells phase sensitive, but the cells show an incorrect 90
      degrees peak shift of orientation tuning under opposite contrast signs. An
      inhibition-dominant version of the RM can generate well-tuned cells across the
      simple-complex spectrum, but it predicts that the net effect of cortical
      interactions is to suppress feedforward excitation across all orientations in
      simple cells. Finally, adding antiphase inhibition used in the MFM into the RM
      produces a most general model. We call this new model the modified recurrent
      model (MRM) and show that this model can also produce well-tuned cells throughout
      the simple-complex spectrum. Unlike the inhibition-dominant RM, the MRM is
      consistent with data from cat V1, suggesting that the net effect of cortical
      interactions is to boost simple cell responses at the preferred orientation.
      These results suggest that the MFM is well suited for explaining orientation
      tuning in simple cells, whereas the standard RM is for complex cells. The
      assignment of the RM to complex cells also avoids conflicts between the RM and
      the experiments of cortical inactivation (done on simple cells) and the spatial
      frequency dependency of orientation tuning (found in simple cells). Because
      orientation-tuned V1 cells show a continuum of simple- to complex-cell behavior,
      the MRM provides the best description of V1 data.

PMID- 16625001
TI  - Identification of an oculomotor biomarker of preclinical Huntington disease.
AB  - The authors examined oculomotor function to identify a biomarker of disease
      progression in genetically confirmed preclinical and early clinical Huntington
      disease (HD). Initiation deficits of voluntary-guided, but not reflexive,
      saccades were characteristic of preclinical HD. Saccadic slowing and delayed
      reflexive saccades were demonstrated in clinical but not preclinical HD. Saccadic
      measures provide biomarkers of disease progression in both preclinical and early
      clinical stages of HD.

PMID- 16625002
TI  - Efficient and repetitive production of hematopoietic and endothelial cells from
      feeder-free monolayer culture system of primate embryonic stem cells.

PMID- 16625003
TI  - Transcriptional regulation of cyclin D2 by the PKA pathway and inducible cAMP
      early repressor in granulosa cells.
AB  - Cyclin D2 (Ccnd2) is an essential gene for folliculogenesis, as null mutation in
      mice impairs granulosa cell proliferation in response to FSH. Ccnd2 mRNA is
      induced during the estrus cycle by FSH and is rapidly inhibited by LH. Yet, the
      responsive elements and transcription factors accounting for the gene expression
      of cyclin D2 in the ovary have not been fully characterized. Using primary
      cultures of rat granulosa cells and immortalized mouse granulosa cells, we
      demonstrate a mechanism for the regulation of cyclin D2 at the level of
      transcription via a PKA-dependent signaling mechanism. The promoter activity of
      cyclin D2 was shown to be induced by FSH and the catalytic alpha subunit of PKA
      (PRKACA), and this activity was repressible by inducible cAMP early repressor
      (ICER), a cAMP response element (CRE) modulator isoform. In silico analysis of
      the mouse, rat, and human cyclin D2 promoters identified two CRE-binding protein
      sites, a conserved proximal element and a less conserved distal element relative
      to the translation start site. The mutation on the proximal element drastically
      decreases the effects of PRKACA and ICER on the promoter activity, whereas the
      mutation on the distal element did not contribute to the decrease in the promoter
      activity. Electrophoretic mobility shift assays and deoxyribonuclease footprint
      analysis confirmed ICER binding to the proximal element, and chromatin
      immunoprecipitation analysis demonstrated the occurrence of this binding in vivo.
      These results showed a CRE within the upstream region of Ccnd2 that is (at least
      partly) implicated in the stimulation and repression of cyclin D2 transcription.
      Finally, our data suggest that ICER involvement in the regulation of granulosa
      cell proliferation as overexpression of ICER results in the inhibition of PRKACA
      induced DNA synthesis.

PMID- 16625004
TI  - Images in clinical medicine. Umbilical-cord prolapse at 29 weeks' gestation.

PMID- 16625005
TI  - Private health care in Canada.

PMID- 16625006
TI  - The NIH budget and the future of biomedical research.

PMID- 16625007
TI  - The challenge of subgroup analyses--reporting without distorting.

PMID- 16625008
TI  - Efficacy and safety of corticosteroids for persistent acute respiratory distress
      syndrome.
AB  - BACKGROUND: Persistent acute respiratory distress syndrome (ARDS) is
      characterized by excessive fibroproliferation, ongoing inflammation, prolonged
      mechanical ventilation, and a substantial risk of death. Because previous reports
      suggested that corticosteroids may improve survival, we performed a multicenter,
      randomized controlled trial of corticosteroids in patients with persistent ARDS.
      METHODS: We randomly assigned 180 patients with ARDS of at least seven days'
      duration to receive either methylprednisolone or placebo in a double-blind
      fashion. The primary end point was mortality at 60 days. Secondary end points
      included the number of ventilator-free days and organ-failure-free days,
      biochemical markers of inflammation and fibroproliferation, and infectious
      complications. RESULTS: At 60 days, the hospital mortality rate was 28.6 percent
      in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and
      29.2 percent in the methylprednisolone group (95 percent confidence interval,
      20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95
      percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent
      confidence interval, 22.8 to 41.7 percent; P=1.0), respectively.
      Methylprednisolone was associated with significantly increased 60- and 180-day
      mortality rates among patients enrolled at least 14 days after the onset of ARDS.
      Methylprednisolone increased the number of ventilator-free and shock-free days
      during the first 28 days in association with an improvement in oxygenation,
      respiratory-system compliance, and blood pressure with fewer days of vasopressor
      therapy. As compared with placebo, methylprednisolone did not increase the rate
      of infectious complications but was associated with a higher rate of
      neuromuscular weakness. CONCLUSIONS: These results do not support the routine use
      of methylprednisolone for persistent ARDS despite the improvement in
      cardiopulmonary physiology. In addition, starting methylprednisolone therapy more
      than two weeks after the onset of ARDS may increase the risk of death.
      (ClinicalTrials.gov number, NCT00295269.).

PMID- 16625009
TI  - Oral ondansetron for gastroenteritis in a pediatric emergency department.
AB  - BACKGROUND: Vomiting limits the success of oral rehydration in children with
      gastroenteritis. We conducted a double-blind trial to determine whether a single
      oral dose of ondansetron, an antiemetic, would improve outcomes in children with
      gastroenteritis. METHODS: We enrolled 215 children 6 months through 10 years of
      age who were treated in a pediatric emergency department for gastroenteritis and
      dehydration. After being randomly assigned to treatment with orally
      disintegrating ondansetron tablets or placebo, the children received oral
      rehydration therapy according to a standardized protocol. The primary outcome was
      the proportion who vomited while receiving oral rehydration. The secondary
      outcomes were the number of episodes of vomiting and the proportions who were
      treated with intravenous rehydration or hospitalized. RESULTS: As compared with
      children who received placebo, children who received ondansetron were less likely
      to vomit (14 percent vs. 35 percent; relative risk, 0.40; 95 percent confidence
      interval, 0.26 to 0.61), vomited less often (mean number of episodes per child,
      0.18 vs. 0.65; P<0.001), had greater oral intake (239 ml vs. 196 ml, P=0.001),
      and were less likely to be treated by intravenous rehydration (14 percent vs. 31
      percent; relative risk, 0.46; 95 percent confidence interval, 0.26 to 0.79).
      Although the mean length of stay in the emergency department was reduced by 12
      percent in the ondansetron group, as compared with the placebo group (P=0.02),
      the rates of hospitalization (4 percent and 5 percent, respectively; P=1.00) and
      of return visits to the emergency department (19 percent and 22 percent, P=0.73)
      did not differ significantly between groups. CONCLUSIONS: In children with
      gastroenteritis and dehydration, a single dose of oral ondansetron reduces
      vomiting and facilitates oral rehydration and may thus be well suited for use in
      the emergency department.

PMID- 16625010
TI  - Clinical practices. Scabies.

PMID- 16625011
TI  - Images in clinical medicine. Bird-mite infestation.

PMID- 16625012
TI  - Case records of the Massachusetts General Hospital. Case 12-2006. A 37-year-old
      man with hemoptysis and a pulmonary infiltrate.

PMID- 16625013
TI  - Lung Inflammation in ARDS--friend or foe?

PMID- 16625014
TI  - Rotavirus vaccines.

PMID- 16625015
TI  - Intensive diabetes treatment and cardiovascular disease.

PMID- 16625016
TI  - Inhaled cyclosporine in lung transplantation.

PMID- 16625017
TI  - Patent foramen ovale and unexplained stroke.

PMID- 16625018
TI  - Aneurysmal subarachnoid hemorrhage.

PMID- 16625019
TI  - Lead shot in the appendix.

PMID- 16625020
TI  - Donor-derived T-cell leukemia after bone marrow transplantation.

PMID- 16625021
TI  - A case of platydeoxia?

PMID- 16625022
TI  - Brief report: assessing the impact of rating scale type, types of items, and age
      on the measurement of school-age children's self-reported quality of life.
AB  - OBJECTIVE: To examine the effect of age, scale, and item type on the reliability
      and reproducibility of children's quality-of-life (QOL) responses. METHODS: The
      TedQL (ability, social, and mood items) was administered to 266 healthy children
      (age range of 5-6 and 7-9 years) at two time points, comparing three rating
      scales (circles, faces, and thermometer). Children were given the same (n = 144)
      or different (n = 122) scales over time. RESULTS: Reliability for total QOL and
      ability items was highest for circles and for social items using the faces. Faces
      and thermometer scales showed highest reproducibility over time. Greater
      agreement over time across different scales was found between circles and faces
      (5-6 years) and thermometer and circles (7-9 years). CONCLUSIONS: For maximum
      internal reliability, circles are recommended for ability items and faces for
      social items. For maximum reproducibility over time, the thermometer is
      recommended for 5-6 years and faces for 7-9 years.

PMID- 16625023
TI  - Externalizing behaviors and minor unintentional injuries in toddlers: common risk
      factors?
AB  - OBJECTIVE: To investigate predictors for externalizing behaviors and minor
      unintentional injuries in toddlers and to examine whether common risk factors can
      be identified. METHODS: Linear regression models were used to investigate the
      contributions of predictors belonging to the domains of child characteristics and
      parental characteristics. Participants were 117 boys (M = 16.9 months) and their
      parents. RESULTS: Two common risk factors for externalizing behaviors and minor
      injuries were identified: maternal low conscientiousness and paternal low self
      control. In addition, children's inhibitory control and dispositional frustration
      as well as maternal externalizing symptoms contributed independently to
      children's externalizing behaviors. CONCLUSIONS: Results supply some evidence for
      the interrelatedness of negative outcomes and on the existence of common risk
      factors. Interventions could aim to address these common risk factors in order to
      pursue a number of goals at the same time, instead of focusing on only one type
      of negative outcome.

PMID- 16625024
TI  - Quantitative trait loci influencing low density lipoprotein particle size in
      African Americans.
AB  - Genomic regions that influence LDL particle size in African Americans are not
      known. We performed family-based linkage analyses to identify genomic regions
      that influence LDL particle size and also exert pleiotropic effects on two
      closely related lipid traits, high density lipoprotein cholesterol (HDL-C) and
      triglycerides, in African Americans. Subjects (n = 1,318, 63.0 +/- 9.5 years, 70%
      women, 79% hypertensive) were ascertained through sibships with two or more
      individuals diagnosed with essential hypertension before age 60. LDL particle
      size was measured by polyacrylamide gel electrophoresis, and triglyceride levels
      were log-transformed to reduce skewness. Genotypes were measured at 366
      microsatellite marker loci distributed across the 22 autosomes. Univariate and
      bivariate linkage analyses were performed using a variance components approach.
      LDL particle size was highly heritable (h(2) = 0.78) and significantly (P <
      0.0001) genetically correlated with HDL-C (rho(G) = 0.32) and log triglycerides
      (rho(G) = -0.43). Significant evidence of linkage for LDL particle size was
      present on chromosome 19 [85.3 centimorgan (cM), log of the odds (LOD) = 3.07, P
      = 0.0001], and suggestive evidence of linkage was present on chromosome 12 (90.8
      cM, LOD = 2.02, P = 0.0011). Bivariate linkage analyses revealed tentative
      evidence for a region with pleiotropic effects on LDL particle size and HDL-C on
      chromosome 4 (52.9 cM, LOD = 2.06, P = 0.0069). These genomic regions may contain
      genes that influence interindividual variation in LDL particle size and
      potentially coronary heart disease susceptibility in African Americans.

PMID- 16625026
TI  - tRNAHis guanylyltransferase adds G-1 to the 5' end of tRNAHis by recognition of
      the anticodon, one of several features unexpectedly shared with tRNA synthetases.
AB  - All eukaryotic tRNA(His) molecules are unique among tRNA species because they
      require addition of a guanine nucleotide at the -1 position by tRNA(His)
      guanylyltransferase, encoded in yeast by THG1. This G(-1) residue is both
      necessary and sufficient for aminoacylation of tRNA by histidyl-tRNA synthetase
      in vitro and is required for aminoacylation in vivo. Although Thg1 is presumed to
      be highly specific for tRNA(His) to prevent misacylation of tRNAs, the source of
      this specificity is unknown. We show here that Thg1 is >10,000-fold more
      selective for its cognate substrate tRNA(His) than for the noncognate substrate
      tRNA(Phe). We also demonstrate that the GUG anticodon of tRNA(His) is a crucial
      Thg1 identity element, since alteration of this anticodon in tRNA(His) completely
      abrogates Thg1 activity, and the simple introduction of this GUG anticodon to any
      of three noncognate tRNAs results in significant Thg1 activity. For tRNA(Phe),
      k(cat)/K(M) is improved by at least 200-fold. Thg1 is the only protein other than
      aminoacyl-tRNA synthetases that is known to use the anticodon as an identity
      element to discriminate among tRNA species while acting at a remote site on the
      tRNA, an unexpected link given the lack of any identifiable sequence similarity
      between these two families of proteins. Moreover, Thg1 and tRNA synthetases share
      two other features: They act in close proximity to one another at the top of the
      tRNA aminoacyl-acceptor stem, and the chemistry of their respective reactions is
      strikingly similar.

PMID- 16625027
TI  - Ranges of ions in metals for use in particle treatment planning.
AB  - In proton and ion radiotherapy, the range of particles is calculated from x-ray
      computed tomography (CT) numbers. Due to the strong absorption of x-rays in a
      metal and a cut-off for large Hounsfield units (HU) in the software of most CT
      scanners, a range calculation in metals cannot be based on the measured HU. This
      is of special importance when metal implants such as gold fillings or hip
      prostheses are close to the treatment volume. In order to overcome this problem
      in treatment planning for heavy charged particles, the correct ranges of ions in
      the metal relative to water have to be assigned in the CT data. Measurements and
      calculations of carbon ion ranges in various metals are presented that can be
      used in treatment planning to allow for a more accurate range calculation of
      carbon ion beams in titanium, steel, tungsten and gold. The suggested values for
      the relative water-equivalent range and their uncertainties are 3.13 (+/-3%) for
      titanium, 5.59 (+/-3%) for stainless steel and 10.25 (+/-4%) for gold.

PMID- 16625028
TI  - The average number of alpha-particle hits to the cell nucleus required to
      eradicate a tumour cell population.
AB  - Alpha-particle emitters are currently being considered for the treatment of
      micrometastatic disease. Based on in vitro studies, it has been speculated that
      only a few alpha-particle hits to the cell nucleus are considered lethal.
      However, such estimates do not consider the stochastic variations in the number
      of alpha-particle hits, energy deposited, or in the cell survival process itself.
      Using a tumour control probability (TCP) model for alpha-particle emitters, we
      derive an estimate of the average number of hits to the cell nucleus required to
      provide a high probability of eradicating a tumour cell population. In simulation
      studies, our results demonstrate that the average number of hits required to
      achieve a 90% TCP for 10(4) clonogenic cells ranges from 18 to 108. Those cells
      that have large cell nuclei, high radiosensitivities and alpha-particle emissions
      occurring primarily in the nuclei tended to require more hits. As the clinical
      implementation of alpha-particle emitters is considered, this type of analysis
      may be useful in interpreting clinical results and in designing treatment
      strategies to achieve a favourable therapeutic outcome.

PMID- 16625029
TI  - A method for pharmacokinetic modelling of dynamic contrast enhanced MRI studies
      of rapidly enhancing lesions acquired in a clinical setting.
AB  - Abnormal microcirculation is a feature of many neoplastic and non-neoplastic
      diseases. Physiological variables that characterize tissue microcirculation
      (capillary permeability and the volume of the extravascular extracellular fluid)
      are altered in pathological states. Pharmacokinetic analysis of dynamic contrast
      enhanced MRI (DCE-MRI) has found a widespread use in the assessment of abnormal
      microcirculation due to the direct link between the contrast agent kinetics and
      underlying microcirculatory properties. A representation of temporal variation of
      contrast agent concentration in blood plasma (C(p)(t)) is central to this
      analysis. In clinical applications of DCE-MRI, signal intensity curves derived
      from rapidly enhancing lesions often display a sigmoid shape during the initial
      phase of contrast uptake and rapid arrival at the equilibrium phase. In this
      work, the features of two principal methods for pharmacokinetic analysis of DCE
      MRI which allow for theoretical representation of C(p)(t) are examined and
      combined to improve analysis of this particular class of DCE-MRI curves. The
      proposed method allows the representation of the initial sigmoid part of the
      enhancement profiles whilst retaining a realistic representation of C(p)(t) based
      on previously published measurements obtained in healthy volunteers. The results
      of the computer simulations indicate that in rapidly enhancing lesions, with the
      transfer constant K(trans) greater than 0.1 min(-1), the DCE-MRI acquisition can
      be restricted to 5 min post-injection and a mono-exponential representation of
      C(p)(t) decay is sufficient. Furthermore, non-ideal bolus delivery can be
      represented as a short constant rate infusion when the tissue under investigation
      exhibits a sigmoid pattern of contrast uptake.

PMID- 16625030
TI  - Measuring the imaged-object distance with a stationary high-spatial-resolution
      scintillation camera.
AB  - A method to measure the detector-to-object distance from the images obtained with
      stationary high-spatial-resolution gamma-ray cameras for in vivo studies has been
      developed. It exploits the shift of the imaged object in the image plane,
      obtained at a certain tilt of the parallel-hole collimator. A linear dependence
      of the image displacement on the distance to the object has been measured using a
      high-spatial-resolution scintillation camera employing an yttrium-aluminium
      perovskite (YAP) scintillator. It is shown that the modified YAP camera can be
      used to obtain three-dimensional information without moving the camera or the
      object. The method could be applied in scintimammography and radioguided surgery,
      in lymphoscintigraphy, as well as in the analysis of the biodistribution of
      radiopharmaceuticals.

PMID- 16625031
TI  - Depth of interaction resolution measurements for a high resolution PET detector
      using position sensitive avalanche photodiodes.
AB  - We explore dual-ended read out of LSO arrays with two position sensitive
      avalanche photodiodes (PSAPDs) as a high resolution, high efficiency depth
      encoding detector for PET applications. Flood histograms, energy resolution and
      depth of interaction (DOI) resolution were measured for unpolished LSO arrays
      with individual crystal sizes of 1.0, 1.3 and 1.5 mm, and for a polished LSO
      array with 1.3 mm pixels. The thickness of the crystal arrays was 20 mm. Good
      flood histograms were obtained for all four arrays, and crystals in all four
      arrays can be clearly resolved. Although the amplitude of each PSAPD signal
      decreases as the interaction depth moves further from the PSAPD, the sum of the
      two PSAPD signals is essentially constant with irradiation depth for all four
      arrays. The energy resolutions were similar for all four arrays, ranging from
      14.7% to 15.4%. A DOI resolution of 3-4 mm (including the width of the
      irradiation band which is approximately 2 mm) was obtained for all the unpolished
      arrays. The best DOI resolution was achieved with the unpolished 1 mm array
      (average 3.5 mm). The DOI resolution for the 1.3 mm and 1.5 mm unpolished arrays
      was 3.7 and 4.0 mm respectively. For the polished array, the DOI resolution was
      only 16.5 mm. Summing the DOI profiles across all crystals for the 1 mm array
      only degraded the DOI resolution from 3.5 mm to 3.9 mm, indicating that it may
      not be necessary to calibrate the DOI response separately for each crystal within
      an array. The DOI response of individual crystals in the array confirms this
      finding. These results provide a detailed characterization of the DOI response of
      these PSAPD-based PET detectors which will be important in the design and
      calibration of a PET scanner making use of this detector approach.

PMID- 16625032
TI  - On the detector arrangement for in-beam PET for hadron therapy monitoring.
AB  - In-beam positron emission tomography (in-beam PET) is currently the only method
      for an in situ monitoring of highly tumour-conformed charged hadron therapy. At
      the experimental carbon ion tumour therapy facility, running at the Gesellschaft
      fur Schwerionenforschung, Darmstadt, Germany, all treatments have been monitored
      by means of a specially adapted dual-head PET scanner. The positive clinical
      impact of this project triggered the construction of a hospital-based hadron
      therapy facility, with in-beam PET expected to monitor more delicate
      radiotherapeutic situations. Therefore, we have studied possible in-beam PET
      improvements by optimizing the arrangement of the gamma-ray detectors. For this,
      a fully 3D, rebinning-free, maximum likelihood expectation maximization algorithm
      applicable to several closed-ring or dual-head tomographs has been developed. The
      analysis of beta(+)-activity distributions simulated from real-treatment
      situations and detected with several detector arrangements allows us to conclude
      that a dual-head tomograph with narrow gaps yields in-beam PET images with
      sufficient quality for monitoring head and neck treatments. For monitoring larger
      irradiation fields, e.g. treatments in the pelvis region, a closed-ring tomograph
      was seen to be highly desirable. Finally, a study of the space availability for
      patient and bed, tomograph and beam portal proves the implementation of a closed
      ring detector arrangement for in-beam PET to be feasible.

PMID- 16625033
TI  - Refractive index of carcinogen-induced rat mammary tumours.
AB  - Near-infrared optical techniques for clinical breast cancer screening in humans
      are rapidly advancing. Based on the computational inversion of the photon
      diffusion process through the breast, these techniques rely on optical tissue
      models for accurate image reconstruction. Recent interest has surfaced regarding
      the effect of refractive index variations on these reconstructions. Although many
      data exist regarding the scattering and absorption properties of normal and
      diseased tissue, no measurements of refractive index appear in the literature. In
      this paper, we present near-infrared refractive index data acquired from N-methyl
      N-nitrosourea-induced rat mammary tumours, which are similar in pathology and
      disease progression to human ductal carcinoma. Eight animals, including one
      control, were employed in this study, yielding data from 32 tumours as well as
      adjacent adipose and connective tissues.

PMID- 16625034
TI  - Nanoparticles as image enhancing agents for ultrasonography.
AB  - Nanoparticles have drawn great attention as targeted imaging and/or therapeutic
      agents. The small size of the nanoparticles allows them to target cells that are
      beyond capillary vasculature, such as cancer cells. We investigated the effect of
      solid nanoparticles for enhancing ultrasonic grey scale images in tissue phantoms
      and mouse livers in vivo. Silica nanospheres (100 nm) were dispersed in agarose
      at 1-2.5% mass concentration and imaged by a high-resolution ultrasound imaging
      system (transducer centre frequency: 30 MHz). Polystyrene particles of different
      sizes (500-3000 nm) and concentrations (0.13-0.75% mass) were similarly dispersed
      in agarose and imaged. Mice were injected intravenously with nanoparticle
      suspensions in saline. B-mode images of the livers were acquired at different
      time points after particle injection. An automated computer program was used to
      quantify the grey scale changes. Ultrasonic reflections were observed from
      nanoparticle suspensions in agarose gels. The image brightness, i.e., mean grey
      scale level, increased with particle size and concentration. The mean grey scale
      of mouse livers also increased following particle administration. These results
      indicated that it is feasible to use solid nanoparticles as contrast enhancing
      agents for ultrasonic imaging.

PMID- 16625035
TI  - Cone beam CT with zonal filters for simultaneous dose reduction, improved target
      contrast and automated set-up in radiotherapy.
AB  - Cone beam CT (CBCT) using a zonal filter is introduced. The aims are reduced
      concomitant imaging dose to the patient, simultaneous control of body scatter for
      improved image quality in the tumour target zone and preserved set-up detail for
      radiotherapy. Aluminium transmission diaphragms added to the CBCT x-ray tube of
      the Elekta Synergytrade mark linear accelerator produced an unattenuated beam for
      a central "target zone" and a partially attenuated beam for an outer "set-up
      zone". Imaging doses and contrast noise ratios (CNR) were measured in a test
      phantom for transmission diaphragms 12 and 24 mm thick, for 5 and 10 cm long
      target zones. The effect on automatic registration of zonal CBCT to conventional
      CT was assessed relative to full-field and lead-collimated images of an
      anthropomorphic phantom. Doses along the axis of rotation were reduced by up to
      50% in both target and set-up zones, and weighted dose (two thirds surface dose
      plus one third central dose) was reduced by 10-20% for a 10 cm long target zone.
      CNR increased by up to 15% in zonally filtered CBCT images compared to full-field
      images. Automatic image registration remained as robust as that with full-field
      images and was superior to CBCT coned down using lead-collimation. Zonal CBCT
      significantly reduces imaging dose and is expected to benefit radiotherapy
      through improved target contrast, required to assess target coverage, and wide
      field edge detail, needed for robust automatic measurement of patient set-up
      error.

PMID- 16625036
TI  - Simplified TRS398 dosimetry protocol for dose determination in high-energy
      electrons beams.
AB  - A method is proposed to simplify the IAEA TRS398 dosimetry code of practice in
      respect to dose determination of high-energy electron beams. The proposed method
      eliminates the use of the intermediate beam quality Q(int) (and beam quality
      correction factor k(Q,Q(int))) applicable for cross calibration and subsequent
      use of the user's chamber for dose determination in water for high-energy
      electron beams. This method allows calculation of the dose to water calibration
      factor for the user's instrument at the reference beam quality N(D)(w,Q0)
      directly from a cross calibration in a high-energy electron beam of quality
      Q(cross) at the user's institute.

PMID- 16625037
TI  - Spectral reconstruction by scatter analysis for a linear accelerator photon beam.
AB  - Pre-existing methods for photon beam spectral reconstruction are briefly
      reviewed. An alternative reconstruction method by scatter analysis for linear
      accelerators is introduced. The method consists in irradiating a small plastic
      phantom at standard 100 cm SSD and inferring primary beam energy spectral
      information based on the measurement with a standard Farmer chamber of scatter
      around the phantom at several specific scatter angles: a scatter curve is
      measured which is indicative of the primary spectrum at hand. A Monte Carlo code
      is used to simulate the scatter measurement set-up and predict the relative
      magnitude of scatter measurements for mono-energetic primary beams. Based on mono
      energetic primary scatter data, measured scatter curves are analysed and the
      spectrum unfolded as the sum of mono-energetic individual energy bins using the
      Schiff bremsstrahlung model. The method is applied to an Elekta/SL18 6 MV photon
      beam. The reconstructed spectrum matches the Monte Carlo calculated spectrum for
      the same beam within 6.2% (average error when spectra are compared bin by bin).
      Depth dose values calculated for the reconstructed spectrum agree with physically
      measured depth dose data to within 1%. Scatter analysis is preliminarily shown to
      have potential as a practical spectral reconstruction method requiring few
      measurements under standard 100 cm SSD and feasible in any radiotherapy
      department using a phantom and a Farmer chamber.

PMID- 16625038
TI  - Investigating the fundamentals of IMRT decomposition using ten simple collimator
      models.
AB  - The fundamentals of IMRT collimation have been studied using ten conceptual
      collimators. Spanning a range of complexities from the LINAC jaws alone to a full
      multi-leaf collimator (MLC), these collimators were designed with two abilities
      in mind: (1) to be able to define arbitrary field shapes, and (2) to be able to
      irradiate multiple, disconnected regions in a single segment. The collimators
      were tested by finding decompositions of random and clinical intensity-modulated
      beams (IMBs), and collimator performance was measured using both the number of
      segments required to complete the IMB and the monitor-unit efficiency of the
      treatment. The decompositions were run on 10 x 10 IMBs with integer bixel values
      randomly between 1 and 10, and clinical IMBs of varying sizes from lung, head and
      neck, and pelvic patients taken from a Pinnacle treatment-planning system.
      Results confirmed that although treatment performance improves with increased
      collimator complexity, it is not solely dependent on the number of segment shapes
      deliverable by the collimator but instead on how well these shapes lend
      themselves to IMRT delivery.

PMID- 16625039
TI  - Simulation and visualization of dose uncertainties due to interfractional organ
      motion.
AB  - In this paper, we deal with the effects of interfractional organ motion during
      radiation therapy. We consider two problems: first, treatment plan evaluation in
      the presence of motion, and second, the incorporation of organ motion into IMRT
      optimization. Concerning treatment plan evaluation, we face the problem that the
      delivered dose cannot be predicted with certainty at the time of treatment
      planning but is associated with uncertainties. We present a method to simulate
      stochastic properties of the dose distribution. This provides the treatment
      planner with information about motion-related risks of different plans and may
      support the decision for or against a treatment plan. This information includes
      the display of probabilities of individual voxels to receive doses from a
      therapeutical interval or above critical levels, as well as a diagram that shows
      the variability of the dose volume histogram. Concerning the incorporation of
      organ motion into IMRT planning, we further analyse the approach of inverse
      planning based on probability distributions of possible patient geometries. We
      consider three different sources of uncertainty, namely uncertainty about the
      amplitude of motion, a systematic error and a random error. We analyse the impact
      of these sources of uncertainty on the optimized treatment plans for prostate
      cancer.

PMID- 16625040
TI  - Comparison of a finite-element multigroup discrete-ordinates code with Monte
      Carlo for radiotherapy calculations.
AB  - Radiotherapy calculations often involve complex geometries such as interfaces
      between materials of vastly differing atomic number, such as lung, bone and/or
      air interfaces. Monte Carlo methods have been used to calculate accurately the
      perturbation effects of the interfaces. However, these methods can be
      computationally expensive for routine clinical calculations. An alternative
      approach is to solve the Boltzmann equation deterministically. We present one
      such deterministic code, Attila. Further, we computed a brachytherapy example and
      an external beam benchmark to compare the results with data previously calculated
      by MCNPX and EGS4. Our data suggest that the presented deterministic code is as
      accurate as EGS4 and MCNPX for the transport geometries examined in this study.

PMID- 16625041
TI  - External beam radiotherapy boosts to reduce the impact caused by edema in
      prostate permanent seed implants.
AB  - In prostate permanent seed implants, it has been shown that edema caused by the
      surgical procedure decreases dose coverage and hence may reduce treatment
      efficacy. This reduction in treatment efficacy has been characterized by an
      increase in tumour cell survival, and biomathematical models have been developed
      to calculate the tumour cell survival increases in seed implanted prostates of
      different edema magnitudes and durations. External beam boosts can be utilized to
      neutralize the negative impact of edema so that originally desired treatment
      efficacy can be achieved. In this study, a linear quadratic model is used to
      determine fractionation sizes of the external beam boosts for both (125)I and
      (103)Pd seed implants. Calculations were performed for prostates of different
      edema magnitudes and durations, and for tumour cells of different repair rates
      and repopulation rates.

PMID- 16625042
TI  - Calculation of stopping power ratios for carbon ion dosimetry.
AB  - Water-to-air stopping power ratio calculations for the ionization chamber
      dosimetry of clinical carbon ion beams with initial energies from 50 to 450 MeV/u
      have been performed using the Monte Carlo technique. To simulate the transport of
      a particle in water the computer code SHIELD-HIT v2 was used, which is a newly
      developed version where substantial modifications were implemented on its
      predecessor SHIELD-HIT v1 (Gudowska et al 2004 Phys. Med. Biol. 49 1933-58). The
      code was completely rewritten replacing formerly used single precision variables
      with double precision variables. The lowest particle transport specific energy
      was decreased from 1 MeV/u down to 10 keV/u by modifying the Bethe-Bloch formula,
      thus widening its range for medical dosimetry applications. In addition, the code
      includes optionally MSTAR and ICRU-73 stopping power data. The fragmentation
      model was verified and its parameters were also adjusted. The present code
      version shows excellent agreement with experimental data. It has been used to
      compute the physical quantities needed for the calculation of stopping power
      ratios, s(water,air), of carbon beams. Compared with the recommended constant
      value given in the IAEA Code of Practice, the differences found in the present
      investigations varied between 0.5% and 1% at the plateau region, respectively for
      400 MeV/u and 50 MeV/u beams, and up to 2.3% in the vicinity of the Bragg peak
      for 50 MeV/u.

PMID- 16625043
TI  - Local frequency dependence in transcranial ultrasound transmission.
AB  - The development of large-aperture multiple-source transducer arrays for
      ultrasound transmission through the human skull has demonstrated the possibility
      of controlled and substantial acoustic energy delivery into the brain parenchyma
      without the necessitation of a craniotomy. The individual control of acoustic
      parameters from each ultrasound source allows for the correction of distortions
      arising from transmission through the skull bone and also opens up the
      possibility for electronic steering of the acoustic focus within the brain. In
      addition, the capability to adjust the frequency of insonation at different
      locations on the skull can have an effect on ultrasound transmission. To
      determine the efficacy and applicability of a multiple-frequency approach with
      such a device, this study examined the frequency dependence of ultrasound
      transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex
      vivo human skulls. Effects beyond those that are characteristic of frequency
      dependent attenuation were examined. Using broadband pulses, it was shown that
      the reflected spectra from the skull revealed information regarding ultrasound
      transmission at specific frequencies. A multiple-frequency insonation with
      optimized frequencies over the entirety of five skull specimens was found to
      yield on average a temporally brief 230% increase in the transmitted intensity
      with an 88% decrease in time-averaged intensity transmission within the focal
      volume. This finding demonstrates a potential applicability of a multiple
      frequency approach in transcranial ultrasound transmission.

PMID- 16625044
TI  - Evaluation of dual-energy subtraction of digital mammography images under
      conditions found in a commercial unit.
AB  - Radiological contrast-to-noise ratio (CNR) is evaluated in subtracted images of
      microcalcifications in breast tissue. CNR is calculated for dual-kVp subtraction
      combining beams available in a Senographe 2000D, assuming single breast
      compression. Spectra were obtained from Boone et al (1997 Med. Phys. 24 1863-73),
      and the study was limited to lowest 25 kV Mo/Mo and highest 40 kV Rh/Rh beams,
      for 2.58 x 10(-4) C kg(-1) (1R) total exposure. For a standard case combining 25
      kVp Mo/Mo and 40 kVp Rh/Rh beams, predicted maximum CNR for 300 microm
      calcification in 5 cm thick, 50% glandular, breast is about 1.2, below Rose's
      criterion for visualization. Total mean glandular doses are about 2.5 cGy for a
      standard case. The effect that input factors might have on predictions has been
      evaluated. Choice between alternative spectra can affect CNR by 50%. Assumed
      calcification composition leads to differences of 67% in calculated CNR, and
      assumed breast tissue composition can alter CNR by 45%; these results are weakly
      dependent on calcification or breast thickness, or on the assumed fraction of
      glandular tissue. CNR values are related to detected spectra effective energy.
      Calculations predict that above 37 kVp Mo/Mo beams are more energetic than Rh/Rh
      at the same kVp, due to beam hardening.

PMID- 16625045
TI  - A physiological model of the interaction between tissue bubbles and the formation
      of blood-borne bubbles under decompression.
AB  - Under decompression, bubbles can form in the human body, and these can be found
      both within the body tissues and the bloodstream. Mathematical models for the
      growth of both types of bubbles have previously been presented, but they have not
      been coupled together. This work thus explores the interaction between the growth
      of tissue and blood-borne bubbles under decompression, specifically looking at
      the extent to which they compete for the common resource of inert gas held in
      solution in the tissues. The influence of tissue bubbles is found to be
      significant for densities as low as 10 ml(-1) for tissues which are poorly
      perfused. However, the effects of formation of bubbles in the blood are not found
      until the density of bubble production sites reaches 10(6) ml(-1). From
      comparison of the model predictions with experimental evidence for bubbles
      produced in animals and man under decompression, it is concluded that the density
      of tissue bubbles is likely to have a significant effect on the number of bubbles
      produced in the blood. However, the density of nucleation sites in the blood is
      unlikely to be sufficiently high in humans for the formation of bubbles in the
      blood to have a significant impact on the growth of the bubbles in the tissue.

PMID- 16625046
TI  - FDTD calculations of specific energy absorption rate in a seated voxel model of
      the human body from 10 MHz to 3 GHz.
AB  - Finite-difference time-domain (FDTD) calculations have been performed to
      investigate the frequency dependence of the specific energy absorption rate (SAR)
      in a seated voxel model of the human body. The seated model was derived from
      NORMAN (NORmalized MAN), an anatomically realistic voxel phantom in the standing
      posture with arms to the side. Exposure conditions included both vertically and
      horizontally polarized plane wave electric fields between 10 MHz and 3 GHz. The
      resolution of the voxel model was 4 mm for frequencies up to 360 MHz and 2 mm for
      calculations in the higher frequency range. The reduction in voxel size permitted
      the calculation of SAR at these higher frequencies using the FDTD method. SAR
      values have been calculated for the seated adult phantom and scaled versions
      representing 10-, 5- and 1-year-old children under isolated and grounded
      conditions. These scaled models do not exactly reproduce the dimensions and
      anatomy of children, but represent good geometric information for a seated child.
      Results show that, when the field is vertically polarized, the sitting position
      causes a second, smaller resonance condition not seen in resonance curves for the
      phantom in the standing posture. This occurs at approximately 130 MHz for the
      adult model when grounded. Partial-body SAR calculations indicate that the upper
      and lower regions of the body have their own resonant frequency at approximately
      120 MHz and approximately 160 MHz, respectively, when the grounded adult model is
      orientated in the sitting position. These combine to produce this second
      resonance peak in the whole-body averaged SAR values calculated. Two resonance
      peaks also occur for the sitting posture when the incident electric field is
      horizontally polarized. For the adult model, the peaks in the whole-body averaged
      SAR occur at approximately 180 and approximately 600 MHz. These peaks are due to
      resonance in the arms and feet, respectively. Layer absorption plots and colour
      images of SAR in individual voxels show the specific regions in which the seated
      human body absorbs the incident field. External electric field values required to
      produce the ICNIRP basic restrictions were derived from SAR calculations and
      compared with ICNIRP reference levels. This comparison shows that the reference
      levels provide a conservative estimate of the ICNIRP whole-body averaged SAR
      restriction, with the exception of the region above 1.4 GHz for the scaled 1-year
      old model.

PMID- 16625047
TI  - Adjuvant effect of the Propionibacterium acnes and its purified soluble
      polysaccharide on the immunization with plasmidial DNA containing a Trypanosoma
      cruzi gene.
AB  - In the present work we investigated the role of killed Propionibacterium acnes or
      a soluble polysaccharide extracted from bacterium cell wall in modulated
      experimental immunization with plasmidial DNA. We used a plasmid, p154/13,
      containing a gene-encoding catalytic domain of Trypanosoma cruzi (T. cruzi) trans
      sialidase. As previously described, immunization of BALB/c mice with p154/13
      elicited humoral, cell-mediated and protective immune responses against T. cruzi
      infection. In this study we describe that both P. acnes and its soluble
      polysaccharide fraction have the ability to modulate the immune response elicited
      by p154/13. Treatment with these adjuvants enhanced specific trans-sialidase Th1
      immune response, as revealed by a lower IgG1/IgG2a ratio and stronger in vitro
      IFN-gamma synthesis by CD4+ T cells. The most important fact was that treatment
      with P. acnes or its soluble polysaccharide fraction in the presence of p154/13
      significantly reduced the peak of parasitemia observed 7 to 8 days after T. cruzi
      challenge. These data suggest that P. acnes or its soluble polysaccharide
      fraction may improve the protective potential of a DNA vaccine against
      experimental T. cruzi infection.

PMID- 16625048
TI  - Molecular typing of Pasteurella pneumotropica isolated from rodents by amplified
      16S ribosomal DNA restriction analysis and pulsed-field gel electrophoresis.
AB  - A total of 52 isolates of Pasteurella pneumotropica obtained from rodents were
      examined for their genetic heterogeneity. On the basis of DNA restriction
      analysis, including amplified 16S ribosomal DNA restriction analysis (ARDRA) and
      pulsed-field gel electrophoresis (PFGE), differences were identified among the
      isolates. ARDRA typing with Hae III revealed 4 different banding patterns of the
      P. pneumotropica isolates. Eighty-two percent of the 23 isolates identified as a
      1 were derived from mice, whereas all the isolates identified as a-3 were derived
      from rats. Most of the isolates, which showed hemolytic activity on blood agar,
      obtained from mice and rats, were identified as a-2 and a-4, respectively. By
      restriction analysis of genomic DNA, Apa I and Not I digestion differentiated 9
      variants and an undiscriminating group. However, no close relation with regard to
      the phenotypic characteristics was observed among the variants. The isolates
      identified as a-2 and a-4 could not be distinguished by PFGE analysis. DNA
      restriction analysis revealed that the genetic diversity of the P. pneumotropica
      isolates was more complex than the phenotypic characteristics among the species,
      and that at least the P. pneumotropica isolates were clearly differentiated into
      4 groups by ARDRA typing with Hae III.

PMID- 16625049
TI  - Virulence-defective strains of Salmonella enterica serovar Typhi as candidates
      for education at level 2 facilities.
AB  - The use of biosafety level 3 pathogens is an essential element of education and
      training at medical schools. We previously reported on invasion-defective strains
      of Salmonella enterica serovar Typhi, GTC 3P408 (DeltainvA, DeltasipB) and GTC
      3P409 (DeltainvA, DeltasipB, and DeltaviaB), as candidates for use in educational
      programs. Vi negative strains of S. enterica serovar Typhi became extremely
      sensitive to complement attack but showed increased invasiveness. Therefore, this
      study was conducted to construct two virulencedefective strains, GTC 3P460
      (DeltainvA, DeltasipB, and DeltarpoS) and GTC 3P461 (DeltainvA, DeltasipB,
      DeltaviaB, and DeltarpoS), of S. enterica serovar Typhi by deleting rpoS from the
      GTC 3P409 and GTC 3P408 strains. Stress tests demonstrated that GTC 3P460 and GTC
      3P461 are sensitive to conditions of starvation, acid stress and oxidative
      stress. These results suggest that these virulence-defective strains have
      difficulty surviving in the gastric environment and in macrophages,
      characteristics that make them ideal candidates for education at level 2
      facilities. Colony morphology and conventional biochemical features of these
      strains are identical to the parent strain S. enterica serovar Typhi GIFU 10007.

PMID- 16625050
TI  - Determination of antifungal activities in serum samples from mice treated with
      different antifungal drugs allows detection of an active metabolite of
      itraconazole.
AB  - To establish an in vitro method of predicting in vivo efficacy of antifungal
      drugs against Candida albicans and Aspergillus fumigatus, the antifungal
      activities of fluconazole, itraconazole, and amphotericin B were determined in
      mouse serum. The minimum inhibitory concentration (MIC) of each drug was measured
      using mouse serum as a diluent. For C. albicans, the assay endpoint of azoles was
      defined as inhibition of mycelial extension (mMIC) and for A. fumigatus, as no
      growth (MIC). The MICs of amphotericin B for both pathogens were defined as the
      MIC at which no mycelial growth occurred. Serum MIC or mMIC determinations were
      then used to estimate the concentration of the drugs in serum of mice treated
      with antifungal drugs by multiplying the antifungal titer of the serum samples by
      the serum (m)MIC. The serum drug concentrations were also determined by HPLC. The
      serum concentrations estimated microbiologically showed good agreement with those
      determined by HPLC, except for itraconazole. Analysis of the serum samples from
      itraconazole-treated mice by a sensitive bioautography revealed the presence of
      additional spots, not seen in control samples of itraconazole. The bioautography
      assay demonstrated that the additional material detected in serum from mice
      treated with itraconazole was an active metabolite of itraconazole. The data
      showed that the apparent reduction in the itraconazole serum concentration as
      determined by HPLC was the result of the formation of an active metabolite, and
      that the use of a microbiological method to measure serum concentrations of drugs
      can provide a method for prediction of in vivo efficacy of antifungal drugs.

PMID- 16625051
TI  - Immunodominant epitope in the C-terminus of a variable major protein in Borrelia
      duttonii, an agent of tick-borne relapsing fever.
AB  - Borrelia duttonii strain Ly was isolated from a child with tick-borne relapsing
      fever in Tanzania. B. duttonii produces variable major proteins (Vmps), which
      undergo antigenic variation. We previously reported transcription of the vmpP
      gene, which is one of the Vmp genes in strain Ly, detected in vitro cultivation.
      In the current study, we purified the recombinant non-lipidated VmpP protein by
      affinity chromatography and produced VmpP polyclonal antibodies. Antigenicity of
      VmpP was examined by Western immunoblot analysis and peptide-based enzyme-linked
      immunosorbent assays. Antigenic epitopes were shown to comprise five regions
      interspersed within the VmpP primary amino acid sequence. Synthetic peptides
      spanning residues of three of five regions, 232-237 (LASIVD), 280-285 (AGGIAL),
      and 350-355 (KAADQQ), reacted strongly with the VmpP-specific antibody and these
      residues were identified as epitopes. In particular, the C-terminal domain
      (KAADQQ) of this protein was immunoreactive. Further research based on our
      results will promote the development of a recombinant vaccine for B. duttonii
      infection.

PMID- 16625052
TI  - Chloroquine inhibits Paracoccidioides brasiliensis survival within human
      monocytes by limiting the availability of intracellular iron.
AB  - The mechanisms used by Paracoccidioides brasiliensis(Pb 18) to survive into
      monocytes are not clear. Cellular iron metabolism is of critical importance to
      the growth of several intracellular pathogens, including P. brasiliensis, whose
      capacity to multiply in mononuclear phagocytes is dependent on the availability
      of intracellular iron. Chloroquine, by virtue of its basic properties, has been
      shown to prevent release of iron from holotransferrin by raising endocytic and
      lysosomal pH, and thereby interfering with normal iron metabolism. Then, in view
      of this, we have studied the effects of CHLOR on P. brasiliensis multiplication
      in human monocytes and its effect on the murine paracoccidioidomycosis. CHLOR
      induced human monocytes to kill P. brasiliensis. The effect of CHLOR was reversed
      by FeNTA, an iron compound that is soluble at neutral to alkaline pH, but not by
      holotransferrin, which releases iron only in an acidic environment. CHLOR
      treatment of Pb 18-infected BALB/c mice significantly reduced the viable fungi
      recovery from lungs, during three different periods of evaluation, in a dose
      dependent manner. This study demonstrates that iron is of critical importance to
      the survival of P. brasiliensis yeasts within human monocytes and the CHLOR
      treatment in vitro induces Pb 18 yeast-killing by monocytes by restricting the
      availability of intracellular iron. Besides, the CHLOR treatment in vivo
      significantly reduces the number of organisms in the lungs of Pb-infected mice
      protecting them from several infections. Thus, CHLOR was effective in the
      treatment of murine paracoccidioidomycosis, suggesting the potential use of this
      drug in patients' treatment.

PMID- 16625053
TI  - Gingipains inactivate a cell surface ligand on Porphyromonas gingivalis that
      induces TLR2-and TLR4-independent signaling.
AB  - Arginine-specific gingipain and lysine-specific gingipain are two major cysteine
      proteinases produced by Porphyromonas gingivalis. To clarify the role of
      gingipains in the interaction between P. gingivalis and the innate immune system,
      CHO reporter cells expressing TLR2 or TLR4 were stimulated with wildtype or
      gingipain-deficient P. gingivalis cells and activation of nuclear factor-kappaB
      in these cells was examined. While CHO/CD14 cells and 7.19 cells, an MD-2
      defective mutant derived from CHO/CD14 cells, failed to respond to wild-type P.
      gingivalis, they responded to gingipain-deficient P. gingivalis. On the other
      hand, CHO/CD14/TLR2 cells responded to both wild-type and gingipain-deficient P.
      gingivalis. These results suggested that gingipains have no effects on TLR2
      dependent signaling from P. gingivalis but have inhibitory effects on TLR2-and
      TLR4-independent signaling in CHO cells. Indeed, the activity of gingipain
      deficient P. gingivalis to induce the activation of 7.19 cells was diminished
      after treatment of the bacterial cells with gingipains. We next partially
      purified bacterial cell components activating 7.19 cells from gingipain-deficient
      P. gingivalis. The activity of the partially purified components was diminished
      by treatment with heat or gingipains. It is also noteworthy that anti-CD14 mAb
      inhibited the activation of 7.19 cells induced by the partially purified
      components. These results indicated that the components of P. gingivalis that
      were able to induce TLR2-and TLR4-independent signaling were inactivated by
      gingipains before being recognized by CD14. The inactivation of the components
      would be helpful for P. gingivalis to escape from the innate immune system.

PMID- 16625054
TI  - Occurrence of the Fimbria Gene hifA in clinical isolates of nonencapsulated
      Haemophilus influenzae.
AB  - The adherence of Haemophilus influenzae to epithelial cells plays a crucial role
      in infections. However, little is known about the occurrence of fimbriae. In this
      study, we examined the distribution of the fimbria gene (hifA) by PCR among 167
      H. influenzae strains isolated from patients with respiratory infections. Almost
      all (163; 98%) of the isolates were nonencapsulated strains. The carriage rate of
      hifA by the nonencapsulated strains was 18.4%. Electron microscopy showed that
      fimbriae were abundantly present on the cell surface of hifA-positive strains
      tested. Only four (2.4%) isolates were encapsulated, all of which were type b and
      did not possess hifA. The present work suggests that fimbriae may play a
      considerable role as adhesins in nonencapsulated H. influenzae strains.

PMID- 16625055
TI  - Analysis of a bacterial lipopolysaccharide-activated serine kinase that
      phosphorylates p65/L-plastin in macrophages.
AB  - We previously identified p65/L-plastin as a phosphorylated protein in LPS
      stimulated macrophages and determined its phosphorylation site. In vitro kinase
      assay using peptide substrates revealed that LPS-stimulated kinase activity
      selectively phosphorylated their serine-5 (Ser-5) residue. Kinase inhibitors for
      cAMP-dependent kinase such as H-89 inhibited the Ser-5 phosphorylation, but cAMP
      was not essential for the kinase activity. The LPS-stimulated kinase activity in
      cytosol fractions of macrophages was recovered as a sharp peak by anion exchange
      chromatography. These findings suggest that an as yet unknown H-89-sensitive
      serine kinase is rapidly activated by LPS stimulation and then phosphorylates
      p65/L-plastin, playing a vital role in macrophage activation.

PMID- 16625056
TI  - Analysis of amphotericin B-induced cell signaling with chemical inhibitors of
      signaling molecules.
AB  - Although amphotericin B (AmB) is a major polyene antibiotic against invasive
      fungal infection, administration to patients sometimes causes inflammatory side
      effects, which limits the usage of the antibiotic. We studied the intracellular
      signaling that was induced by AmB. p65 (RelA) of nuclear factor-kappaB (NF
      kappaB), a well-known signaling molecule as an inducer of proinflammatory
      cytokines, was phosphorylated by AmB in RAW264.7 cells, a monocyte-like cell
      line. Among chemical inhibitors of signaling molecules, U-73122 (phospholipase C
      (PLC) inhibitor), Go6976 (protein kinase C (PKC) inhibitor), BAPTA-AM (calcium
      chelator), LFM-A13 (Bruton's tyrosine kinase (Btk)-specific inhibitor), and PP2
      (c-Src kinase inhibitor) suppressed AmB-induced phosphorylation of p65 and
      translocation of p65 into the nucleus. U-73122 and Go6976 reduced AmB-mediated
      induction of proinflammatory cytokines (tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-6) in RAW264.7 cells. Furthermore, AmB-induced activation of NF
      kappaB was observed in toll-like receptor (TLR) 2-expressed cells, and the
      activation of NF-kappaB was inhibited by U-73122, whereas peptidoglycan-induced
      NF-kappaB activation, which was also dependent on TLR2, was not inhibited by U
      73122. Finally, U-73122 partially suppressed in vivo production of TNF-alpha and
      IL-6 induced by AmB administration in BALB/c mice. These results suggested that
      the signaling from AmB stimulation to proinflammatory cytokine production is
      mediated by TLR2, Btk, PLC, PKC, c-Src and NF-kappaB. These signaling molecules
      may become a target for chemotherapy suppressing AmB-induced proinflammatory
      cytokine production.

PMID- 16625057
TI  - Functional analysis of spoT, relA and dksA genes on quinolone tolerance in
      Pseudomonas aeruginosa under nongrowing condition.
AB  - To assess the contribution of ppGpp in antibiotic tolerance to quinolone in
      Pseudomonas aeruginosa, knockout mutants of the genes involved or linked with the
      stringent response, such as relA, spoT and dksA, were constructed and
      investigated for their antibiotic susceptibility to quinolones. The survival of
      the dksA and spoT mutants in the presence of 8 microg/ml of ofloxacin and 1
      microg/ml of ciprofloxacin were shown to be approximately 20-180 and 10-40 times
      respectively, higher than the same for the wild type strain. The intracellular
      levels of ppGpp determined with high performance liquid chromatography (HPLC)
      demonstrated that spoT and dksA mutants possess higher basal levels of ppGpp. The
      data suggest that elevated basal levels of ppGpp may be responsible for rendering
      these mutants tolerant to quinolones and expand the importance of ppGpp as an
      antimicrobial target in P. aeruginosa.

PMID- 16625058
TI  - Trends in medical care costs, coverage, use, and access: research findings from
      the Medical Expenditure Panel Survey.

PMID- 16625059
TI  - Workers who decline employment-related health insurance.
AB  - BACKGROUND: Families of workers who decline coverage represent a substantial
      share of the uninsured and publicly-insured population in the United States.
      OBJECTIVE: We examined health status, access to health care, utilization, and
      expenditures among families that declined health insurance coverage offered by
      employers using data from the Medical Expenditure Panel Survey for 2001 and 2002.
      RESULTS: We found differences in insurance status for adults and children among
      families with offers. We found that among low-income families with offers,
      children are less likely to have private insurance compared with adults. However,
      the majority of children who decline private insurance end up with public
      coverage, whereas most of adults who decline offers remain uninsured. Decliners
      are more likely to report poor health, yet they are also less likely to have high
      cost medical conditions. Families declining coverage have weaker preferences for
      insurance than families that take up. Although access to care is lower among the
      decliners who remain uninsured, decliners with public insurance have similar
      access to care as those with private insurance. Families turning down coverage
      are more likely to face high expenditure burdens as a percentage of income and
      more likely to have financial barriers to care. Families who decline coverage
      rely heavily on the safety net. Public sources and uncompensated care account for
      72% of total expenditures among adults who decline coverage. CONCLUSIONS: Our
      results suggest that policy initiatives aimed at increasing take up among workers
      need to take into account the incentives workers face given the availability of
      care through public sources and uncompensated care.

PMID- 16625060
TI  - Access to care and utilization among children: estimating the effects of public
      and private coverage.
AB  - OBJECTIVES: We examine the relationship between health insurance coverage and
      children's access to and utilization of medical care. Access measures we study
      are having a usual source of care (USC) and lacking a USC for financial or
      insurance reasons. We also examine indicators for ambulatory visits, well-child
      visits, dental visits, emergency room use, and inpatient hospital stays. METHODS:
      We pool data from the first 7 years of the Medical Expenditure Panel Survey
      (MEPS), 1996 to 2002. Pooling yields a large sample of children, enabling us to
      analyze access and utilization using simple descriptive statistics, multivariate
      analysis, and instrumental variables estimation (IV). IV estimation is of
      particular interest given the possibility of bias caused by confounding factors
      (such as child health or parent attitudes) and measurement error in insurance
      coverage. We also compare estimates from IV linear probability models to
      estimates from IV probit with residual inclusion. RESULTS: As previous studies
      have found, public and private coverage are both associated with large increases
      in access and utilization. Simple mean comparisons suggest that private coverage
      has a larger effect than does public coverage. Differences between public and
      private coverage are reduced (and often reversed) when we control for other
      characteristics of children and their families. IV coverage effect estimates from
      both linear probability and residual inclusion probit models are substantially
      greater than conventional estimates across a wide range of access and utilization
      measures. CONCLUSIONS: Despite concerns that conventional estimates overstate the
      impact of coverage on access and use, our results suggest that the reverse may be
      true. One explanation may be that conventional estimates are biased toward zero
      due to error in the reporting of insurance coverage. The magnitude of the
      coverage effects we find highlights the importance of reducing uninsurance among
      children.

PMID- 16625061
TI  - Trends in prescription drug expenditures by Medicaid enrollees.
AB  - OBJECTIVE: As prescription drug expenditures consume an increasingly larger
      portion of Medicaid budgets, states are anxious to control drug costs without
      endangering enrollees' health. In this report, we analyzed recent trends in
      Medicaid prescription drug expenditures by therapeutic classes and subclasses.
      Identifying the fastest growing categories of drugs, where drugs are grouped into
      clinically relevant classes and subclasses, can help policymakers decide where to
      focus their cost containment efforts. METHODS: We used data from the Medical
      Expenditure Panel Survey linked to a prescription drug therapeutic classification
      system, to examine trends between 1996/1997 and 2001/2002 in utilization and
      expenditures for the noninstitutionalized Medicaid population. We separated
      aggregate trends into changes in population with use and changes in expenditures
      per user, and percent generic. We also highlighted differences within the
      Medicaid population, including children, adults, disabled, and elderly. RESULTS:
      We found rapid growth in expenditures for antidepressants, antipsychotics,
      antihyperlipidemics, antidiabetic agents, antihistamines, COX-2 inhibitors, and
      proton pump inhibitors and found evidence supporting the rapid take-up of new
      drugs. In some cases these increases are the result of increased expenditures per
      user and in other cases the overall growth also comes from an increase in the
      population with use. CONCLUSIONS: Medicaid programs may want to reassess their
      cost-containment policies in light of the rapid take-up of new drugs. Our
      analysis also identifies areas in which more information is needed on the
      comparative effectiveness of new versus existing treatments.

PMID- 16625062
TI  - Children and antibiotics: analysis of reduced use, 1996-2001.
AB  - OBJECTIVES: We investigated trends in antibiotic use by U.S. children, from 1996
      to 2001, a period that followed the launch of national campaigns to promote the
      appropriate use of antibiotics. DATA AND METHODS: We used nationally
      representative data from the Medical Expenditure Panel Survey for the years 1996
      2001 to examine trends in antibiotic use and the contributions of changes in
      ambulatory visits and prescribing to these trends. We investigated trends in the
      use of antibiotics overall and for respiratory tract infections and examined
      these trends within subgroups of children defined by race/ethnicity and income.
      RESULTS: From 1996 to 2001, the proportion of children with antibiotic use
      overall and for respiratory tract infections decreased by 8.5 percentage points
      and 5.1 percentage points, respectively. Overall, the probability of a child
      having an ambulatory visit did not change. The decrease in overall antibiotic use
      resulted entirely from an increase in the probability that a child had an
      ambulatory visit(s) with no antibiotic use. By contrast, a decline in the
      probability that a child had a visit for a respiratory tract infection accounted
      for two-thirds of the reduction in antibiotic use for these conditions. The
      decline in overall use for white-other non-Hispanic children (-10.2 percentage
      points) was more than double the decline for black non-Hispanic or Hispanic
      children. CONCLUSION: Children's use of antibiotics, overall and for respiratory
      tract infections, showed significant declines from 1996 to 2001. The apparent
      response to campaigns to reduce inappropriate antibiotic use was widespread as
      reductions in use were found in all subgroups of children examined.

PMID- 16625063
TI  - A closer look at the managed care backlash.
AB  - BACKGROUND: Much anecdotal evidence exists regarding the managed care backlash of
      the late 1990s, but limited empirical evidence is available. OBJECTIVES: Using a
      unique series of employer surveys, we examined trends in enrollment rates in
      health maintenance organizations (HMOs) and other plan types between 1997 and
      2003. RESEARCH DESIGN: We present enrollment rates in employer-sponsored health
      plans by plan type. These plan-level enrollment rates are disaggregated by
      whether or not enrollees had a choice of plan types and by firm size and year.
      SUBJECTS: Employees who were enrolled in employer-sponsored health insurance in
      private sector establishments. RESULTS AND CONCLUSIONS: Although we found
      evidence of a decline in the popularity of HMOs, it occurred later than indicated
      in earlier studies. In our data, HMO enrollment rates fell from roughly 32% to
      26% between 1997 and 2003, with most of the decline occurring after 2001. Earlier
      studies reported that the decline in HMO enrollment rates occurred between 1996
      and 1998, and between 2000 and 2001. In addition, an interesting story emerged
      when we examined trends by firm size. We found evidence of a decline in the HMO
      enrollment rate for large employers starting in 1998. However, this was offset by
      an increase in the HMO enrollment rate in small employers, which explains the
      stability in our figures before 2002. Our data also indicated that when workers
      were given a choice between an HMO and other plan types, workers increasingly
      opted for the non-HMO plan during this time period.

PMID- 16625064
TI  - The utility of extended longitudinal profiles in predicting future health care
      expenditures.
AB  - BACKGROUND: Health care spending is highly concentrated. Prediction models that
      accurately identify the characteristics of individuals most likely to incur high
      levels of health expenditures in a subsequent year are important analytical and
      statistical tools. OBJECTIVES: This study examined the capacity of alternative
      models to predict the likelihood of incurring high levels of medical expenditures
      in a subsequent year. This effort also evaluated the utility of an additional
      year of longitudinal information. SUBJECTS: A nationally representative sample
      from the Medical Expenditure Panel Survey (MEPS). METHODS: The MEPS longitudinal
      data are used to examine the persistence of high expenditures during a 2-year
      period. With the unique linkage of the MEPS to the National Health Interview
      Survey, the utility of an additional year of data also was examined. Resultant
      models were evaluated in terms of sensitivity, specificity, and predictive
      capacity. RESULTS: Only modest marginal gains in discrimination capacity were
      realized from the use of extended longitudinal profiles from the National Health
      Interview Survey, relative to information on prior year characteristics.
      CONCLUSIONS: Our results highlight the continuing concentration of health care
      expenditures during the period 1996 to 2002 and reveal some attenuation in
      magnitude in the tail of this distribution over time. Further, our results
      provide evidence of the utility of probabilistic models as prediction tools to
      identify individuals likely to incur high levels of expenditures in future years.
      Predictive capacity does not suffer when restricted to a single year of prior
      information.

PMID- 16625065
TI  - Using the SF-12 health status measure to improve predictions of medical
      expenditures.
AB  - BACKGROUND: Relatively few studies have used self-reported health status in
      models to predict medical expenditures, and many of these have used the SF-36.
      OBJECTIVES: We sought to examine the ability of the briefer SF-12 measure of
      health status to predict medical expenditures in a nationally representative
      sample. METHODS: We used data from the 2000-2001 panel of the Medical Expenditure
      Panel Study. Respondents (n = 5542) completed the SF-12 in a questionnaire.
      Interviews obtained data on demographics and selected chronic conditions. Data on
      expenditures incurred subsequent to the interview were obtained in part from
      provider records. We examined different regression model specifications and
      compared different statistical estimation techniques. RESULTS: Adding the SF-12
      to a regression model improved the prediction of subsequent medical expenditures.
      In a model with only age and gender, adding the SF-12 increased R from 0.06 to
      0.13. The coefficients for the Physical Component Summary (PCS) and the Mental
      Component Summary (MCS) of the SF-12 for this model were -0.045 (P < 0.01) and 
      0.012 (P < 0.01), respectively. In a model including demographic characteristics,
      chronic conditions, and previous expenditures, adding the SF-12 increased the R
      from 0.26 to 0.29. The coefficients for the PCS and the MCS for this model were 
      0.025 (P < 0.001) and -0.005 (P = 0.15), respectively. A single general health
      status question performed almost as well as the full SF-12. Models estimated
      using ordinary least squares had undesirable properties. In terms of R, a
      generalized linear model (GLM) with a Poisson variance function was consistently
      superior to a GLM with a gamma variance function. CONCLUSIONS: Information on
      self-reported health status is useful in predicting medical expenditures. The
      extent to which the SF-12 adds predictive power over a comprehensive array of
      diagnostic data remains to be examined.

PMID- 16625066
TI  - Explaining racial and ethnic disparities in health care.
AB  - OBJECTIVES: The substantial racial and ethnic disparities in access to and use of
      health services are well documented. A number of studies highlight factors such
      as health insurance coverage and socioeconomic differences that explain some of
      the differences between groups, but much remains unexplained. We build on this
      previous research by incorporating additional factors such as attitudes about
      health care and neighborhood characteristics, as well as separately analyzing
      different Hispanic subgroups. METHODS: We use the Oaxaca-Blinder regression-based
      method to decompose differences among racial and ethnic groups in 3 measures
      related to access, quantifying the portion explained by each of a number of
      underlying characteristics and the differences that remain unexplained. We use
      data from the 2000 and 2001 Medical Expenditure Panel Survey (MEPS), a nationally
      representative survey of the noninstitutionalized U.S. population. We link these
      data to detailed neighborhood characteristics from the Census Bureau and local
      provider supply data from the Health Services Resource Administration (HRSA).
      RESULTS: Consistent with earlier studies, we find insurance status and
      socioeconomic differences explain a significant part of the disparities.
      Additionally, neighborhood racial and ethnic composition account for a large
      portion of disparities in access, and language differences help explain observed
      disparities in the use-based access measure. However, much of the differences
      between racial and ethnic groups remain unexplained. We also found substantial
      variation in the level of disparities among different groups of Hispanics.
      CONCLUSIONS: Researchers and policymakers may need to broaden the scope of
      factors they consider as barriers to access if the goal of eliminating
      disparities in health care is to be achieved.

PMID- 16625067
TI  - Reports of fewer activity limitations: recovery, survey fatigue, or switching
      respondent?
AB  - BACKGROUND: Very little is known about the validity and reliability of disability
      dynamics reported in household surveys, and some researchers argue that
      measurement error likely plays a large part in reported recovery from disability.
      OBJECTIVES: We assessed the reliability of reported recovery from activity
      limitations elicited from 2 types of questions. We assessed competing hypotheses
      explaining reported recoveries from disability: people are less likely to recover
      from more severe disabilities, switching between self- and proxy-response affects
      reported recovery, and survey fatigue reduces reported disability. METHODS: Using
      the second panel of the Medical Expenditure Panel Survey, we estimated kappas for
      2 types of questions in the same interview about limitations in activities of
      daily living and instrumental activities of daily living. We estimated
      multinomial logit models of consistently reported recovery, consistently reported
      ongoing limitations, and inconsistent responses. Recovery is a function of
      severity, switching respondent, measures of survey burden (such as family size),
      age, and education. RESULTS: Within an interview, we found substantial
      reliability for both instrumental activities of daily living and activities of
      daily living limitations (kappa = 0.62 and 0.70, respectively). Sample members
      with more severe disabilities are less likely to report recovery, which is
      consistent with accurate reporting. Controlling for severity, the type of
      respondent affects reported recovery. Measures of survey burden did not affect
      reports. CONCLUSION: Researchers can be confident in reports of recovery in the
      Medical Expenditure Panel Survey, especially when disability status was self
      reported in both interviews. Researchers may also want to control for proxy
      respondents and switching respondents in their analyses.

PMID- 16625068
TI  - Cutaneous plasmacytosis: A report of five cases with immunohistochemical
      evaluation for HHV-8 expression.
AB  - Cutaneous plasmacytosis is a rare disorder that typically affects middle-aged to
      older individuals of Asian, particularly Japanese, descent. Clinically, it is
      characterized by multiple asymptomatic red-brown plaques and nodules on the
      trunk. Lymphadenopathy and hypergammaglobulinemia may be present. Histologically,
      the lesions show a moderately dense superficial and deep perivascular infiltrate
      composed predominantly of mature plasma cells without atypia or light chain
      restriction. We report our experience with five additional cases, including
      results of immunohistochemical studies for human herpes virus 8.

PMID- 16625070
TI  - Differential expression of smooth muscle myosin, smooth muscle actin, h
      caldesmon, and calponin in the diagnosis of myofibroblastic and smooth muscle
      lesions of skin and soft tissue.
AB  - The diagnosis of low-grade and pseudosarcomatous spindle cell lesions of skin and
      soft tissue can sometimes be problematic; in particular, distinction between
      fibroblastic, myofibroblastic, and smooth muscle proliferations can occasionally
      pose difficulties on routine histologic examination. We have applied a panel of
      immunohistochemical markers to a series of spindle cell lesions of skin and soft
      tissue to assess the utility of the differential expression of smooth muscle and
      myofibroblastic-associated markers. Twenty-eight cases of nodular fasciitis, 42
      cases of fibromatosis, and 3 cases of myofibroblastic sarcoma were stained with
      antibodies against smooth muscle actin (SMA), smooth muscle myosin (SMMS),
      calponin, and high-molecular weight caldesmon (h-caldesmon). For comparison, 12
      cases of cutaneous leiomyoma and 8 cases of leiomyosarcomas involving superficial
      soft tissues and fascia were studied with the same panel of antibodies. Thirty
      eight of 42 cases of fibromatosis were positive for SMA, 42/42 cases were
      positive for calponin, 39/42 cases were negative for SMMS, and all cases were
      negative for h-caldesmon. All cases of nodular fasciitis were positive for SMA
      and calponin, and all were negative for h-caldesmon and SMMS. All cases of
      myofibroblastic sarcoma were positive for SMA and 2/3 cases for calponin, and
      were negative for SMMS and h-caldesmon. All cases of cutaneous leiomyoma and
      leiomyosarcoma were positive for all 4 markers tested. Our results demonstrate a
      remarkably consistent pattern of reactivity of muscle and myofibroblastic
      associated markers in lesions predominantly composed of myofibroblastic spindle
      cells, characterized by positive staining for SMA and calponin and absence of
      reactivity for SMMS and h-caldesmon. Application of this panel of stains may be
      of aid in the differential diagnosis of low-grade myofibroblastic lesions such as
      nodular fasciitis and fibromatosis from smooth muscle tumors of skin and soft
      tissue. This panel may additionally be of assistance in the diagnosis of
      myofibroblastic sarcoma.

PMID- 16625069
TI  - Immunohistochemical distinction between merkel cell carcinoma and small cell
      carcinoma of the lung.
AB  - We assessed the usefulness of several immunohistochemical stains in
      distinguishing these two neoplasms, including cytokeratin 7, cytokeratin 20
      (CK20), neuron-specific enolase, chromogranin, synaptophysin, neurofilaments
      (NF), thyroid-transcription factor-1 (TTF-1), CD56 antigen, S-100 protein,
      vimentin, c-erbB-2 oncoprotein, and CD117 antigen. All 13 cases of Merkel cell
      carcinoma evaluated were positive for CK20, and negative for TTF-1. Twelve of 13
      Merkel cell carcinoma cases were positive for NF. Eleven of 13 cases of small
      cell lung carcinoma were positive for TTF-1. All small cell lung carcinoma cases
      were negative for NF, and all but one were negative for CK20. In terms of the
      remaining antigens, there were no differences of significance between the two
      neoplasms. These findings suggest that a set of three immunohistochemical stains,
      including CK20, NF, and TTF-1, is useful in affording a distinction between
      Merkel cell carcinoma and small cell lung carcinoma.

PMID- 16625071
TI  - Circumscribed palmar hypokeratosis: new observations.
AB  - Circumscribed hypokeratosis is a characteristic depression both clinically and
      histopathologically that was originally described as representing a distinctive
      acquired epidermal malformation of volar skin. To date, 16 patients with this
      entity have been reported. On the basis of clinical features and histopathologic
      findings in 4 new patients, coupled with information about some of the previously
      reported patients, there is evidence to suggest that this dermatosis could be
      secondary to trauma.

PMID- 16625072
TI  - Pretibial pruritic papular dermatitis: A distinctive cutaneous manifestation in
      response to chronic rubbing.
AB  - We describe the clinico-pathologic features of 44 patients with a peculiar
      pretibial pruritic papular dermatitis (PPPD). Clinically, PPPD consists of
      discrete, roundish, extremely pruritic papules with a smooth surface caused by
      the delicate and persistent rubbing of pretibial skin. Histologically, PPPD
      showed minimal compact orthokeratosis, flattening of the rete ridges, a
      superficial and mid-dermal perivascular and interstitial infiltrate of
      lymphocytes, histiocytes, eosinophils and multinucleated fibroblasts, and
      thickened collagen bundles in haphazard array in the superficial dermis. The
      clinical picture of PPPD closely resembled that of lichen simplex
      chronicus/circumscribed neurodermatitis or lichen amyloidosus. Histologically,
      the absence of uneven psoriasiform epidermal hyperplasia, marked compact
      orthokeratosis, hypergranulosis, and coarse bundles of collagen arranged in
      vertical streaks in the papillary dermis distinguished PPPD from lichen simplex
      chronicus, whereas the lack of amyloid deposits in the dermal papillae
      differentiated PPPD from lichen amyloidosus. We suggest that PPPD is an unusual
      morphologic expression of gentle and chronic rubbing of pretibial skin with
      distinctive histopathologic features.

PMID- 16625073
TI  - Histopathological differences between early and old lesions of hyperkeratosis
      Lenticularis Perstans (Flegel's disease).
AB  - A case of hyperkeratosis lenticularis perstans (Flegel's disease) was studied
      histopathologically comparing early and old lesions. The age of the lesions were
      judged by both the patient's history and direct observation. The histopathologic
      and immunophenotypic features of a new lesion were essentially in accordance with
      previous findings. However, the old lesion had obviously different pathologic
      features. These included the absence of epidermal atrophy and infiltrate in the
      upper dermis under the lesion. Ultrastructural studies revealed that the presence
      of many normal-appearing membrane-coating granules in the keratinocytes of the
      old lesion, whereas the organelles were not found in the keratinocytes of the
      early lesion.

PMID- 16625074
TI  - Adenocarcinoma of mammary-like glands of the vulva: Report of a case and review
      of the literature.
AB  - Mammary-like glands are a poorly recognized structure of normal vulvar skin.
      Adenocarcinomas arising from these glands are rare and represent a distinct
      clinicopathologic entity that must be distinguished from metastatic tumors. We
      reviewed 19 cases reported in the literature and describe a 51-year-old patient
      with a long-standing nodule on her right interlabial sulcus. Excisional biopsy
      and Mohs micrographic surgery demonstrated an infiltrating adenocarcinoma of the
      mammary-like glands involving the dermis and subcutis. On review of all 20 cases,
      the mean age at diagnosis was 59.6 years, the labia majora were involved in 13
      cases (65%), and the mean lesional size was 2.5 cm. The tumor's histologic
      patterns varied greatly, although the histomorphologic similarity among this
      neoplasm, sweat gland carcinomas, and invasive extramammary Paget disease
      suggested a morphologic spectrum among these tumors. Criteria for establishing
      the diagnosis of adenocarcinoma of mammary-like glands include identifying
      transition zones between normal mammary-like glands and adenocarcinomatous areas.
      This tumor is best categorized as a locally aggressive neoplasm with a low risk
      for widespread metastasis. Use of aggressive surgical therapeutic regimens,
      particularly in the case of tumors localized to the skin, must be reassessed,
      especially given the likelihood of long-term morbidity with such regimens. In our
      patient, successful Mohs micrographic surgery suggests that alternate management
      may be adopted for tumors localized to the skin, especially in elderly patients.

PMID- 16625075
TI  - Unusual hyperplasia of anogenital mammary-like glands.
AB  - Anogenital mammary-like glands, although known to exist (as ectopic breast
      tissue) as early as 1872, have only recently been thoroughly studied and
      suggested to be the possible origin for various neoplastic (benign and malignant)
      and reactive conditions that show a striking homology with lesions in the breast.
      Reported herein is an unusual benign lesion involving anogenital mammary-like
      glands in the perineal area of a 41-year-old woman. The lesion is unique in that
      it does not fully fit into any of the previously recognized conditions affecting
      anogenital mammary-like glands nor has it an apparent well-defined mammary
      counterpart. Microscopically, at first glance the lesion appeared as a cluster of
      extended anogenital mammary-like glands of variable complexity and a lobular
      architecture, which probably resulted from a compact proliferation of closely
      situated ducts with small, round lumens (when cut transversally). When cut
      longitudinally, some of these tiny ducts appeared to bud from larger ductal
      structures, resembling so-called satellitosis in the breast and this gave a
      fibroadenomatous appearance to the areas. In addition, there were adenosis-like
      areas. This lesion extends the spectrum of changes seen in anogenital mammary
      like glands.

PMID- 16625076
TI  - Pigmented eccrine poroma occurring on the scalp: Derivation of melanocytes in the
      tumor.
AB  - We describe a man with a pigmented poroma on the scalp mimicking a pigmented
      melanocytic nevus. Histopathological examination showed that melanocytes were
      mostly distributed at the periphery of the tumor masses. It is suggested that
      melanocytes in the tumor masses may have migrated from the adjacent epidermis.

PMID- 16625077
TI  - Tubular adenoma of the skin with follicular and sebaceous differentiation: A
      report of two cases.
AB  - The main controversies regarding tubular apocrine adenoma and papillary eccrine
      adenoma are whether they are two distinct entities or are the very same tumor,
      and if so, which lineage of differentiation (apocrine versus eccrine) it pursues.
      We report two cases of tubular adenoma with follicular and, in one case,
      additionally, sebaceous differentiation. The features in both cases indicated
      apocrine differentiation of the tubular component. One patient was a 60-year-old
      woman with a 1-year history of a solitary nodule on the scalp. The other patient
      was a 48-year-old woman with a solitary nodule of unknown duration located on the
      back. In both patients, the tumors were surgically removed. The patients were
      alive and well 2.5 and 2 years after surgery, respectively. The histologic
      features that both cases had in common included the combination of a tubular
      adenoma, foci of follicular differentiation, and areas of immature squamous
      metaplasia. In case 1, follicular differentiation was seen in the form of strands
      of basaloid cells surrounded by a stroma resembling the embryonic perifollicular
      sheath. Some aggregates of basaloid cells were juxtaposed with small collections
      of plump fibroblasts, imparting a resemblance to rudimentary follicular germs
      associated with follicular papillae. Many minute lumens surrounded by more
      eosinophilic cells were seen within the strands. In case 2, follicular
      differentiation was seen as several infundibulocystic structures surrounded by
      isthmic epithelium housing scattered mature sebocytes. In addition, there were
      areas reminiscent of desmoplastic trichoepithelioma (columnar trichoblastoma). In
      both cases, the areas with immature squamous metaplasia were represented by solid
      nodules that were mostly devoid of lumens and a peripheral basal/myoepithelial
      cell layer. In conclusion, these two cases of cutaneous tubular adenoma with
      accompanying follicular and sebaceous differentiation give further support to the
      proposition that the majority of these neoplasms have apocrine differentiation.
      Rare cases occurring in the sites normally devoid of apocrine glands may
      represent the eccrine counterpart.

PMID- 16625078
TI  - Incidental granular parakeratosis associated with dermatomyositis.
AB  - A 43-year-old patient presented with a 4-month history of intermittently
      occurring symmetrical and slightly scaling erythematous plaques in his zygomatic
      regions. Because of polymyositis in the patient's history, the skin lesions were
      thought to be a manifestation of dermatomyositis. The skin biopsy revealed a
      sparse superficial perivascular infiltrate of lymphocytes, which was associated
      with telangiectases and both discrete vacuolar alteration and smudging of the
      dermal-epidermal junction. These findings were consonant with dermatomyositis. In
      addition to these features focal granular parakeratosis was present. The
      histopathologic presence of granular parakeratotic corneocytes above a zone of
      orthokeratosis and the absence of clinical features of granular parakeratosis
      indicate the granular parakeratosis is incidental.

PMID- 16625079
TI  - Diffuse dermal angiomatosis: A previously undescribed pattern of immunoglobulin
      and complement deposits in two cases.
AB  - Two cases of diffuse dermal angiomatosis are reported in middle-aged women. This
      rare disease of unknown origin is characterized by increased dermal angiomatosis
      and ulceration. The clinical and histologic presentations of the presently
      reported lesions were typical for this disorder. Endothelial cells exhibited a
      normal immunophenotype. The perivascular basement membranes showed a distribution
      of collagen alpha chains typical for blood vessels, but not for lymphatics.
      Immunohistochemistry revealed other undescribed features. At the site of the
      clinical lesions, linear and granular deposits of immunoglobulins A and M, and
      complement were found around the vessels and at the dermal-epidermal junction.
      The same deposits were also found restricted to the dermal-epidermal junction in
      the peripheral clinically intact skin. No serological signs of auto-immune
      disorder were detected in one patient. A monoclonal gammopathy was disclosed in
      the other patient. A pattern of immunoreactant deposits similar to that disclosed
      in the two patients was not found in the control specimens, and has not been
      described so far in other types of vascular hyperplasia and neoplasia. A
      pathogenic role of these deposits is unsettled and should be further explored.

PMID- 16625080
TI  - Sebaceous hyperplasia overlying a dermatofibroma.
AB  - Epithelial changes overlying dermatofibromas are well recognized. The presence of
      sebaceous differentiation overlying a dermatofibroma is unusual. We report two
      patients with sebaceous hyperplasia overlying a dermatofibroma and discuss
      possible mechanisms for induction of the epithelium and adnexa by the mesenchyme
      in a dermatofibroma.

PMID- 16625081
TI  - Reticulated acanthoma with sebaceous differentiation.
AB  - Reticulated acanthoma with sebaceous differentiation (RASD) is characterized by
      the reticulated proliferation of spinous cells with aggregates of mature
      sebocytes in the bases of the strands of the keratinocytes, often linking rete
      ridges. Here, we report the first case reported as RASD. A 55-year-old woman
      presented with a 15-year history of a slightly pruritic patch on the upper back,
      and the histology was typical for RASD. She had been bothered by a yellow
      discharge from the tumor. Skin tumors with sebaceous differentiation are
      occasionally associated with Muir-Torre syndrome. However, immunohistochemical
      staining for mutS homolog 2 (MSH-2) and mutL homolog 1 (MLH-1) showed positive
      staining within the nuclei of sebaceous cells and cells in the dermis. Therefore,
      it is most likely that the present case is not associated with Muir-Torre
      syndrome.

PMID- 16625082
TI  - NGFR-positive desmoplastic melanomas with focal or absent S-100 staining: Further
      evidence supporting the use of both NGFR and S-100 as a primary
      immunohistochemical panel for the diagnosis of desmoplastic melanomas.
AB  - The histologic diagnosis of desmoplastic melanoma can be challenging in
      circumstances in which biopsy specimens are small, or there are unsuspected
      clinical settings, re-excision scars, and unusual sites. This is particularly
      true when the overlying junctional component is absent or the spindle cells lack
      melanin pigment. In these instances, the importance of immunohistochemistry
      cannot be overemphasized. S-100 protein is the primary immunohistochemical stain
      used for this purpose, with a sensitivity approaching 90%. HMB-45, although a
      more specific marker for melanocytes, is less sensitive and often negative in
      these cases. In addition, NGFR, a marker of Schwannian differentiation, has been
      shown to be a useful confirmatory stain for desmoplastic melanoma, with staining
      intensity comparable with, or better than that of S-100 protein. We report 2
      cases of desmoplastic melanomas that stained only focally and weakly with S-100
      protein, but showed diffuse and intense staining with NGFR. In both cases, S-100
      staining could have been interpreted as non-confirmatory, thus misguiding the
      diagnosis. We suggest that NGFR can be a useful complementary marker to S-100 in
      those desmoplastic melanomas in which staining for S100 protein is only focal or
      weak.

PMID- 16625083
TI  - Histologic patterns of polyethylene glycol-liposomal doxorubicin-related
      cutaneous eruptions.
AB  - Polyethylene glycol (PEG)-liposomal doxorubicin (Stealth R, Doxil) is a
      formulation of doxorubicin, which is encapsulated in liposomes formulated with
      PEG. It is favored in the palliative setting over doxorubicin because of its
      generally favorable side effect profile. Adverse reactions are predominantly skin
      eruptions. We report 3 cases of women with breast cancer undergoing treatment
      with liposomal doxorubicin who developed palmar-plantar erythrodysesthesia and
      diffuse morbilliform eruptions. Biopsies in the 2 cases demonstrated vacuolar
      interface dermatitis with epidermal dysmaturation and the third case suggested a
      drug eruption. Additionally, we report a woman with metastatic breast cancer who
      developed a similar morbilliform eruption soon after completing a regimen of
      liposomal doxorubicin. The biopsy revealed an atypical squamous proliferation
      showing epidermal dysmaturation with focal evidence of interface damage. Both
      clinician and pathologist alike should be cognizant of this cutaneous eruption,
      as well as the histologic patterns.

PMID- 16625084
TI  - Facial granulomas secondary to Dermalive microimplants: Report of a case with
      histopathologic differential diagnosis among the granulomas secondary to
      different injectable permanent filler materials.
AB  - Wrinkle reduction and the correction of skin defects using injectable aesthetic
      microimplants are now widely performed by dermatologists and plastic surgeons. In
      recent years, dermal filler substances containing polymer particle suspensions
      such as Bioplastique, Artecoll, and Dermalive are the most commonly used
      materials. These microimplants are permanent, non-biodegradable, and generally
      well tolerated, although various adverse reactions are still possible. We
      describe here a patient with facial granulomas secondary to Dermalive injections
      for correction of naso-labial folds and wrinkles. The particular shape of the
      injected particles allows for correct identification of the implanted material.
      Therefore, histopathologic examination is the best means to obtain the correct
      diagnosis of foreign body granuloma and to identify the type of filler particles.
      We discuss the histopathologic differential diagnosis among the granulomas
      secondary to the most commonly used aesthetic permanent filler materials.

PMID- 16625085
TI  - Disseminated dermatosis with pruritic plaques and patches.

PMID- 16625086
TI  - Herpes incognito most commonly is herpes zoster and its histopathologic pattern
      is distinctive!
AB  - Infections of the skin by herpesviruses do not always present themselves in
      typical fashion. Conventional microscopy is used routinely to confirm infection
      by herpesviruses, but sometimes typical signs such as multinucleated epithelial
      cells or "ghosts" of them are not encountered in a specimen (so-called herpes
      incognito). We studied 35 patients in whom infection with herpesviruses was
      differentially diagnosed clinically but in whom a biopsy specimen had been taken
      for confirmation. Only those patients in whom histopathologic findings had been
      interpreted as being "not diagnostic" of herpesvirus infection by 2 independent
      dermatopathologists were included. Clinical and histopathologic findings were
      correlated with results from polymerase chain reaction studies on formalin-fixed
      paraffin-embedded tissue. Polymerase chain reaction revealed herpesvirus-specific
      DNA in 12 of 35 specimens, 10 being varicella zoster virus (VZV) positive, 1
      herpes simplex virus (HSV)-2 positive, and 1 HSV-1 positive. Ten of these 12
      cases presented themselves in very similar fashion (8 VZV, 1 HSV-1, 1 HSV-2). All
      lesions were macular or papular and typified mostly by dense perivascular and
      sparse interstitial superficial and deep infiltrates of lymphocytes, sometimes
      assuming a patchy lichenoid pattern. Infiltrates were prominent in and around
      adnexal structures, often peppering follicles, sebaceous glands, and eccrine
      glands. Lymphocytes were also found in the lower part of the epidermis
      accompanied by a combination of spongiosis and vacuolar alteration. The papillary
      dermis was often edematous; extravasated erythrocytes in variable numbers were a
      common finding. Lymphocytes sometimes had large and polygonal nuclei. Neutrophils
      and nuclear dust were present occasionally; eosinophils were rare. We conclude
      that herpes incognito most commonly is herpes zoster and its histopathologic
      pattern is distinctive.

PMID- 16625087
TI  - Crypt dysplasia with surface maturation: a clinical, pathologic, and molecular
      study of a Barrett's esophagus cohort.
AB  - Little is known regarding the significance of esophageal biopsies that show
      dysplasia-like atypia limited to the bases of the crypts, without involvement of
      the surface epithelium in Barrett's esophagus (BE). The aim of this study was to
      evaluate the clinical, pathologic, immunohistochemical, and molecular
      characteristics of basal crypt dysplasia-like atypia (BCDA) with surface
      maturation in surveillance endoscopic mucosal biopsies to gain insight into its
      biologic significance. The Seattle Barrett's Esophagus Project is a prospective
      cohort study in which patients and their biopsies have been evaluated
      prospectively for clinical, pathologic, and molecular markers. As part of
      continued surveillance of the cohort, 206 consecutive BE patients were evaluated
      prospectively for BCDA between July 1, 2001 and August 13, 2003; 15 patients had
      BCDA (prevalence rate = 7.3%). These 15 patients were evaluated for clinical,
      pathologic, and immunohistochemical (p53 and MIB-1) features during the study
      period (2001-2003) as well as associations with clinical, pathologic, and
      molecular markers [17p(TP53) loss of heterozygosity (LOH), 9p(p16) LOH,
      tetraploidy, and aneuploidy] that were detected previously in the same patients
      in the cohort study (1983-2001). All BE patients with BCDA (male-to female ratio,
      12:3; mean age, 72 years; mean length of BE, 7.0 cm; mean duration of BE, 95.1
      months), except 2 (87%), had dysplasia or adenocarcinoma detected in biopsies
      either prior to or concurrent to the one that contained BCDA. In contrast, only
      112 of 191 (59%) controls had neoplasia during the same time period (59%, P =
      0.05). The difference between BCDA and controls was particularly significant with
      regard to the association with high-grade dysplasia (P = 0.004). Compared with
      adjacent nonatypical and nondysplastic (metaplastic) BE, areas of BCDA showed a
      significantly elevated prevalence rate of p53 positivity (60% vs. 13%, P<0.02)
      and a significantly elevated total crypt and basal crypt MIB-1 proliferation rate
      (P<0.001). Indeed, the MIB-1 proliferation rate in the basal portion of the
      crypts in BCDA was similar to that detected in conventional low- or high-grade
      dysplasia. Patients with BCDA showed a significantly increased rate of 17p(TP53)
      LOH (P = 0.016), aneuploidy (P = 0.004), and a trend in increased 9p(p16) LOH (P
      = 0.08), compared with control patients without BCDA. The clinical, pathologic,
      immunohistochemical, and molecular abnormalities were similar in BCDA cases that
      were considered low-grade versus those considered high-grade by histologic
      evaluation, except that high-grade cases tended to be older (79 years vs. 68
      years, P = 0.06). BCDA with surface maturation, in mucosal biopsies from patients
      with BE, is an uncommon but significant pathologic change that shows a variety of
      proliferative and molecular abnormalities and has a high association with
      conventional dysplasia and/or adenocarcinoma. Based on these findings, BCDA
      warrants further investigation as a possible subtype of true dysplasia despite
      the morphologic appearance of surface maturation.

PMID- 16625088
TI  - The prognostic significance of fibrosarcomatous transformation in
      dermatofibrosarcoma protuberans.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a superficial tumor characterized by
      high rates of local recurrence and a small risk of metastasis. Fibrosarcomatous
      (FS) areas rarely arise in DFSP, and considerable controversy exists as to
      whether these tumors have a higher risk of metastasis than the typical DFSP. The
      aim of this study was to reappraise the prognostic significance of FS changes in
      DFSP by analyzing 41 patients from the consultation files of our institution. The
      study included 23 females and 18 males, with a median age of 48 years (range, 16
      100 years). Eighteen lesions were located on the trunk, 16 on the extremities,
      and 7 on the head/neck region. All tumors were treated with local excision, and
      the surgical margins were considered positive for tumor in 22 of 39 cases (56%).
      Fibrosarcomas arose de novo in 38 cases and as a recurrence in 3 cases. All
      tumors involved the dermis and subcutis, and the FS component comprised 5% to 95%
      of the tumor area (median, 60%). Mitotic rates of the FS component (median, 20
      mitoses/10 high-power fields [HPFs]; range, 5-48/10 HPFs) were considerably
      higher than those of the neighboring DFSP component (0-2 mitoses/10 HPFs).
      Immunohistochemical analyses showed that CD34 expression was stronger and more
      extensive in the DFSP component (97% positive; median intensity, 3+) than in the
      FS component (81% positive; median intensity, 2+). The MIB-1 labeling index was
      higher in the FS areas (median, 20%; range, 5%-45%) than in the DFSP areas (<3%).
      Expression of p53 was present in 92% of the FS areas and in only 3% of adjacent
      DFSP areas. Follow-up data revealed that 8 patients had local recurrences, 4
      patients (10%) had metastases, and 2 patients died of disease. None of the
      variables evaluated, including margin status, FS proportion, and mitotic count,
      correlated with disease progression. We demonstrate that FS change in DFSP is a
      form of tumor progression that carries an increased risk of metastasis over
      classic DFSP and is associated with gains of p53 mutations and increased
      proliferative activity.

PMID- 16625090
TI  - Mammary NOS-type sarcoma with CD10 expression: a rare entity with features of
      myoepithelial differentiation.
AB  - We present an extensive immunohistochemical analysis of 7 mammary sarcomas that
      did not fit into any specific soft tissue sarcoma category. Histologically, they
      were composed of spindle cells with highly pleomorphic nuclei and abundant
      mitoses. Our immunohistochemical antibody panel included pan-cytokeratin (CK),
      basal cell type CKs (34betaE12, CK5/6, CK14, CK17) and vimentin antibodies,
      antibodies to established (SMA, CD10, p63, S-100, maspin, calponin, GFAP, SM
      myosin), and novel (CD29, 14-3-3sigma) myoepithelial markers, as well as
      antibodies to CD34, desmin, h-caldesmon, steroid receptors (estrogen,
      progesterone, androgen), and EGFR (Her-1). Whereas CKs, CD34, desmin, and h
      caldesmon were not expressed, all tumors were positive for CD10 and vimentin.
      CD29 and SMA were observed in 3 cases each (43%), and p63 and calponin in 2 cases
      each (29%). Other myoepithelial markers and steroid receptors were absent, except
      androgen receptors, which were expressed in one sarcoma. Five sarcomas showed
      positivity for EGFR. The distinction of specific, histogenetically defined
      sarcoma entities (such as leiomyosarcoma, angiosarcoma, liposarcoma) from NOS
      type sarcoma with CD10 expression is usually clear-cut because the former exhibit
      a characteristic histomorphology and immunoprofile. Phyllodes tumors with stromal
      overgrowth or recurrent phyllodes tumors lacking epithelial structures as well as
      periductal stromal sarcomas can be ruled out by their frequent expression of CD34
      and negativity for myoepithelial markers. The most important differential
      diagnosis is sarcomatoid metaplastic carcinoma because its treatment includes
      axillary lymphadenectomy. Since some NOS-type sarcomas with CD10 expression and
      most metaplastic carcinomas show positivity for CD29, SMA, and p63, differential
      diagnosis can be extremely difficult and requires extensive immunohistochemical
      evaluation for CKs and additional myoepithelial markers such as S-100, 14-3
      3sigma, and maspin. The immunophenotype of NOS-type sarcomas with CD10 expression
      suggests that these neoplasms represent a mammary sarcoma variant with
      myoepithelial features.

PMID- 16625089
TI  - Gastric graft-versus-host disease revisited: does proton pump inhibitor therapy
      affect endoscopic gastric biopsy interpretation?
AB  - Accurate diagnosis of gastrointestinal graft-versus-host disease (GvHD) is
      important, as it contributes significantly to postallogeneic stem cell transplant
      (SCT) morbidity and mortality. To test the hypothesis that proton pump inhibitor
      (PPI) therapy may interfere with histologic evaluation of gastric GvHD by
      inducing apoptosis, we evaluated epithelial apoptotic body counts in antral and
      fundic biopsies from SCT recipients and control patients, both taking and not
      taking PPIs at the time of endoscopic biopsy. Hematoxylin and eosin-stained
      slides of gastric biopsies from 130 patients (75 allogeneic SCT with GvHD on
      clinical and histologic grounds, and a comparison group of 55 age- and sex
      matched nontransplant patients with histologically normal gastric biopsies) were
      reviewed. The groups were further stratified into patients taking (PPI+) and not
      taking PPIs (PPI-) at the time of biopsy. Apoptotic bodies (AB)/10 (400 x) high
      power fields (HPF) were quantified for each case. Mean apoptotic body counts were
      then calculated for each case group. Seventy antral cases (31 control and 39
      transplant) were also evaluated via gastrin immunohistochemistry, and the mean
      number of gastrin positive cells/400 x HPF calculated. In the PPI- groups,
      apoptosis was increased in biopsies from transplant patients, compared with
      controls, both in antral and fundic mucosa. In PPI+ patients, there was
      significantly more apoptosis in the gastric body in transplant patients than in
      controls. However, comparing antral biopsies from control and transplant PPI+
      patients, there was no significant difference in AB quantitation. More apoptosis
      was seen in antral biopsies from PPI+ control patients when compared with PPI-
      control patients (P = 0.009). Mean numbers of gastrin positive cells/400 x HPF
      were increased in both control and transplant patients taking PPIs (85 and 58,
      respectively) compared with samples from those patients not taking PPIs (48 and
      51, respectively). PPI therapy is associated with increased apoptosis in antral
      biopsies and may interfere with the evaluation of GvHD in biopsies from this
      site. A similar increase in apoptosis was not seen in fundic biopsies; biopsy of
      the gastric fundus rather than antrum may be preferable for the diagnosis of
      upper gastrointestinal GvHD.

PMID- 16625091
TI  - Autoimplants in serous borderline tumors of the ovary: a clinicopathologic study
      of 30 cases of a process to be distinguished from serous adenocarcinoma.
AB  - The clinical and pathologic features of serous borderline tumors (SBTs) with
      autoimplants (AIs) were studied with emphasis on their relation to survival,
      ovarian SBT with a micropapillary pattern, and their distinction from serous
      adenocarcinoma. The 30 patients ranged in age from 17 to 70 years (mean, 35.8
      years). Two had stage I disease, 10 had stage II disease, and 18 had stage III
      disease. Twenty-five patients had bilateral ovarian tumors. In 28 cases, AIs were
      present on the surface of the neoplasm or between exophytic surface tumor
      papillae; in 2 cases, AIs were between papillae within intracystic tumor. The AIs
      consisted of single cells or glands and clusters of cells with mild to moderate
      nuclear atypia within a fibroblastic stroma; the stroma dominated over the
      epithelium in extent within the AI. In many cases, the epithelial cells in the AI
      had abundant eosinophilic cytoplasm. All but 2 of the patients had coexisting
      noninvasive peritoneal implants; 3 of them also had invasive peritoneal implants.
      Six of the SBTs had a micropapillary pattern; 3 of these were stage III and 3
      stage II tumors. Clinical follow-up was available for 11 patients. Eight were
      alive and well after 4 to 7 years (mean, 5 years); 3 of these patients had stage
      II disease and 5 had stage III disease. Three were dead of disease after 7 to 12
      years (mean, 9 years). Two patients who died of disease had stage III disease,
      and 1 of them had invasive implants. The third patient had stage II disease,
      invasive implants, and the tumor was of the micropapillary type. Our study
      indicates that the majority of patients with SBT with AI have stage II or III
      disease and abundant exophytic tumor. SBTs with AI had a micropapillary pattern
      in 20% of the cases. AIs do not appear to have an adverse impact on survival when
      controlled for peritoneal implant type and for this reason must be distinguished
      from true stromal invasion in serous carcinoma, a misdiagnosis sometimes made, or
      seriously entertained, initially in these cases. Features that favor AI over
      carcinoma arising in an SBT are 1) a location between tumor papillae or on the
      ovarian surface 2) a predominance of stroma over epithelial cells, and 3) the
      "borderline" cytologic appearance of epithelial cells.

PMID- 16625092
TI  - h-Caldesmon, a useful positive marker in the diagnosis of pleural malignant
      mesothelioma, epithelioid type.
AB  - Although a large number of immunohistochemical markers that can facilitate the
      differential diagnosis between epithelioid pleural mesothelioma and lung
      adenocarcinoma involving the pleura have proven to be valuable, no single
      antibody has demonstrated absolute sensitivity and/or specificity in making this
      distinction. Using immunohistochemical analysis with h-caldesmon, a specific
      marker for smooth muscle tumors, we examined 70 cases of epithelial mesotheliomas
      and 70 cases of lung adenocarcinomas. In addition, immunohistochemistry for
      muscle markers, such as desmin, alpha-smooth-muscle actin, muscle-specific actin,
      myoglobin, myogenin, myosin, and MyoD-1, was performed on all mesothelioma cases.
      Reactivity for h-caldesmon was obtained in 68 (97%) of the 70 epithelial
      mesotheliomas, but in none of the adenocarcinoma cases. All mesothelioma cases
      were found to be negative for the other muscle markers examined. We conclude that
      h-caldesmon is a highly sensitive and specific marker and suggest its inclusion
      in the immunohistochemical panel for the differential diagnosis of epithelioid
      mesothelioma versus lung adenocarcinoma.

PMID- 16625093
TI  - Hodgkin lymphoma-like posttransplant lymphoproliferative disorder (HL-like PTLD)
      simulates monomorphic B-cell PTLD both clinically and pathologically.
AB  - Although Hodgkin lymphoma-like posttransplantation lymphoproliferative disorder
      (HL-like PTLD) has been grouped with classic Hodgkin lymphoma type PTLD (HL
      PTLD), controversy remains as to whether it is truly a form of HL or whether it
      should be more appropriately classified as a form of B-cell PTLD. Because only
      few cases of HL-like PTLD have been reported, their pathologic nature and
      clinical behavior have not been well defined. This report characterized 5 cases
      of HL-like PTLD with respect to their immunophenotype, EBV status, clonality, and
      clinical outcome. All of the patients were male, with ages ranging from 1.5 to 55
      years at diagnosis. PTLD developed from 4 months to 6 years following solid organ
      transplantation (3 hearts, 1 kidney, 1 liver), and involved both nodal and
      extranodal sites. All were EBV-related (EBER+) with the large neoplastic cells
      CD20/CD79a positive but CD15 negative. Immunoglobulin gene rearrangements were
      detected in 3 of 5 tested. All patients were managed by initial
      reduction/withdrawal of immunosuppression, with 2 also receiving chemotherapy for
      non-HL. Three patients died of progressive disease within 2 to 3 months after
      diagnosis, 1 is alive and well 2 years later, and the fifth was disease free but
      died of unrelated causes (graft coronary disease) 2 years later. We conclude
      that, although HL-like PTLD morphologically simulates classic HL PTLD, there are
      important immunophenotypic, molecular genetic, and clinical differences,
      suggesting it is in fact most often a B-cell PTLD. Distinction between HL and HL
      like PTLD may be important for clinical management and prognosis.

PMID- 16625094
TI  - Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic,
      immunohistochemical, and molecular genetic study of 906 cases before imatinib
      with long-term follow-up.
AB  - Gastrointestinal (GI) stromal tumors (GISTs), the specific KIT- or PDFGRA
      signaling driven mesenchymal tumors, are the most common mesenchymal tumors of
      the GI tract. This study analyzed 1091 tumors originally classified as smooth
      muscle tumors of the small intestine (including jejunum or ileum and excluding
      duodenum), and found that 906 (83%) of these were GISTs. The GIST patients had
      55:45 male-to-female ratio with a median age of 59 years (range, 13-94 years).
      Only 0.6% of tumors occurred before the age of 21 years and 13.6% before the age
      of 40 years. The tumors varied from 0.3 to 40 cm (median, 7.0 cm) and most
      commonly presented with GI bleeding or acute abdomen; 18% were incidentally
      detected. Histologically, the tumors were relatively monotypic with spindle cell
      (86%), epithelioid (5%), or mixed patterns (9%). Skeinoid fibers were present in
      44% of cases, and their presence was associated with a favorable course. Most
      epithelioid tumors were malignant, and this morphology sometimes emerged from
      less cellular and less mitotically active spindle cell tumors, suggesting that it
      represented a transformation. KIT was immunohistochemically detected in 98%, CD34
      in 40%, smooth muscle actin in 34%, desmin in 0.2%, and S-100 protein in 14% of
      the tumors tested. Outcome was strongly dependent on tumor size and mitotic
      activity, with an overall 39% tumor-related mortality, twice that for gastric
      GISTs. Only <3% of tumors <5 cm and < or = 5 mitoses/50 HPF metastasized, whereas
      86% of tumors >10 cm and >5 mitoses/50 HPF metastasized. In stark contrast to
      corresponding gastric tumors, tumors >10 cm with mitotic activity < or = 5/50 HPF
      and those < or = 5 cm with mitoses >5/50 HPF had a high metastatic rate (>50%);
      tumors >5 cm < or = 10 cm with low mitotic rate had a 24% metastatic rate. The
      median survival times of patients with low mitotic rate tumors who died of
      disease decreased by increasing tumor size. KIT exon 11 mutations were detected
      in 90 cases, exon 9 mutation in 17 cases, and exon 17 mutation in 1 case; the
      presence of mutation or mutation type was not prognostically significant. There
      were no PDGFRA exon 12 or 8 mutations. Systematic data on prognosis of small
      intestinal GISTs of various size and mitotic activity categories can be helpful
      in management and surveillance of patients with these tumors.

PMID- 16625095
TI  - Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma
      (AITL): a new diagnostic marker providing evidence that AITL derives from
      follicular helper T cells.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) represents a distinct entity among
      peripheral T-cell lymphomas (PTCLs). The cellular origin of AITL remains unknown,
      although a possible derivation from follicular helper T cells (TFH) has been
      suggested based on the CD4/Bcl-6 phenotype. It has been recently shown that
      expression of CXCL13, a chemokine critically involved in B-cell migration into
      germinal centers, is characteristic of TFH cells, as compared with other T helper
      subsets. We compared CXCL13 expression in 29 AITLs, 20 PTCLs, unspecified, 10
      anaplastic large cell lymphomas (ALCL), and 4 other PTCLs. We showed that CXCL13
      is expressed by AITL (29 of 29, 100%) and a subset of PTCL, unspecified (6 of 20,
      30%), which all showed borderline features with AITL, but in only 1 of 10 (10%)
      ALCLs, and 0 of 4 other PTCLs. Two-color immunostainings further showed that
      CXCL13 was found in the cytoplasm of atypical CD5-positive T cells that expressed
      CD10. We conclude that CXCL13 expression is a common characteristic of AITL,
      which can help to delineate the morphologic spectrum of the disease, and further
      supports its derivation from TFH cells. CXCL13 expression may also provide an
      additional useful tool for the diagnosis of AITL.

PMID- 16625096
TI  - Giant cell tumor of the extrahepatic biliary tree: a clinicopathologic study of 4
      cases and comparison with anaplastic spindle and giant cell carcinoma with
      osteoclast-like giant cells.
AB  - We report four previously undescribed primary giant cell tumors of the
      extrahepatic biliary tree and morphologically compare them with 10 anaplastic
      spindle and giant cell carcinomas with osteoclast-like giant cells of the
      gallbladder. Two giant cell tumors were located in the distal common bile duct;
      one in the cystic duct and one in the gallbladder. The 3 patients with bile duct
      tumors were male, and the only patient with a gallbladder tumor was a female. The
      age of the patients ranged from 45 to 60 years with an average of 55 years. The
      patients with bile duct tumors presented with biliary obstruction, and the
      patient with a gallbladder tumor presented with symptoms of cholelithiasis and a
      gallbladder mass. Histologically, the tumors were similar to giant cell tumors of
      bone. They consisted of a mixture of mononuclear and multinucleated osteoclast
      like giant cells. The mononuclear cells showed no atypical features, and their
      nuclei were similar to those of the multinucleated giant cells. CD163
      immunoreactivity was restricted to the mononuclear cells, whereas CD68 and HAM 56
      labeled only the multinucleated osteoclast-like giant cells. The mononuclear
      cells were EMA-positive but did not express cytokeratins. Follow-up showed that 3
      patients were alive and disease-free 3.7 to 7 years after surgery. The anaplastic
      spindle and giant cell carcinomas contained a fewer number of osteoclast-like
      giant cells, and their mononuclear cells showed considerable variation in size
      and shape, marked cytologic atypia, and numerous mitotic figures. They were
      focally cytokeratin positive (AE1/AE3; CAM 5.2) and did not label with CD163,
      CD68, and HAM 56. The benign osteoclast-like giant cells showed immunoreactivity
      for CD68 and HAM 56 but were negative for CD163 and cytokeratins. Giant cell
      tumors of the extrahepatic biliary tree are benign true histiocytic neoplasms
      that should be distinguished from the highly lethal anaplastic spindle and giant
      cell carcinomas with osteoclast-like giant cells by detailed cytologic analysis
      and immunohistochemical stains for CD163, CD68, HAM 56, and cytokeratins.

PMID- 16625097
TI  - Clinicopathologic analysis of solid papillary carcinoma of the breast and
      associated invasive carcinomas.
AB  - Solid papillary carcinomas (SPCs) are uncommon tumors composed of circumscribed
      large cellular nodules separated by bands of dense fibrosis. The aim of this
      study was to further elucidate the characteristics of SPC, the types and
      significance of invasive carcinomas associated with these tumors, and the long
      term clinical outcome. Fifty-eight SPCs were analyzed (mean follow-up, 9.4
      years). Cases were divided into three groups: 1) SPC only (32.7%), 2) SPC with
      extravasated mucin (8.6%), and 3) SPC with invasive components (58.7%) consisting
      of neuroendocrine-like (29.5%), colloid (23.5%), ductal not otherwise specified
      (14.5%), lobular (3%), tubular (3%), or mixed (26.5%). The mean age was 72 years.
      All were estrogen receptor positive and 86% were histologic grade 1. The total
      size of the tumor measured 0.3 to 15 cm. In the group with invasive carcinoma,
      the size of invasion was 0.1 to 4 cm. Axillary nodes were involved in 13% of the
      cases (6 of 46); all of these had an invasive component in the primary tumor.
      Local recurrence was seen in 5 patients, all from the group with invasive
      carcinoma. Overall, 11.7% died of their tumor, 1 to 4 years after diagnosis
      (mean, 2.3 years); none of them belongs to the group of noninvasive SPC. Five of
      the 6 patients who died of tumor had invasive components. The sixth patient who
      died with "metastatic signet-ring cell carcinoma" at 10 years was in the group of
      patients with SPC with extravasated mucin where the SPC lesion had prominent
      signet-ring cell features. In conclusion, SPCs are heterogeneous lesions that
      arise in older women and have an indolent behavior. Lymph node and distant
      metastases are uncommon and generally limited to cases with (conventional)
      invasive components.

PMID- 16625098
TI  - Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes
      mellitus.
AB  - Reported are the clinical and pathologic features of glycogenic hepatopathy, a
      pathologic overloading of hepatocytes with glycogen that is associated with
      poorly controlled diabetes mellitus. Fourteen cases were studied by stains,
      including hematoxylin and eosin, trichrome, periodic acid-Schiff, and periodic
      acid-Schiff with diastase. Ultrastructural analysis was performed in 2 cases.
      Medical records were reviewed for clinical presentations, laboratory findings,
      and clinical outcomes. The individuals ranged from 8 to 25 years of age. All had
      type I diabetes mellitus with poor glycemic control. The clinical presentations
      included hepatomegaly, abdominal pain, and elevated transaminases (range, 50-1600
      IU/L). The transaminases were dramatically elevated in 3 cases to greater than 10
      times the upper limit of normal. All biopsies showed diffusely pale staining
      hepatocytes on hematoxylin and eosin stains, with excessive glycogen accumulation
      demonstrated by periodic acid-Schiff stains. Ultrastructural examination revealed
      marked glycogen accumulation in the cytoplasm and nuclei. Most cases showed no
      evidence for fatty liver disease: steatosis was absent in 12 of 14 cases, simple
      steatosis was seen in 1 of 14 cases, and mild steatohepatitis was present in 1 of
      14 cases. Mallory hyaline was absent in all cases, acidophil bodies were only
      rarely seen, and inflammation was absent or minimally present. Fibrosis was
      typically absent, with only 2 cases demonstrating focal mild fibrosis. Three
      patients had adequate follow-up and demonstrated improvement of liver enzyme
      levels with control of blood glucose. We conclude that glycogenic hepatopathy can
      cause hepatomegaly and significant transaminase elevations in individuals with
      type I diabetes mellitus. The pathology is distinct from steatohepatitis.

PMID- 16625099
TI  - Gastric siderosis: patterns and significance.
AB  - Recently, we encountered 2 cases of diffuse iron deposition in gastric antral and
      fundic glandular epithelium, which in 1 patient eventually led to the diagnosis
      of hemochromatosis. Gastric mucosal siderosis (GS) has previously been described
      in hemochromatosis patients, alcoholics, and in association with iron
      medications. However, the prevalence of various patterns of iron deposition in
      the gastric mucosa and their clinical significance have not been studied in
      detail. The 2 index cases mentioned above and 500 additional consecutive gastric
      biopsies examined over a period of 8 months at our institution were stained for
      iron by the Prussian blue method. In addition, all patients with genetic
      hemochromatosis diagnosed by liver biopsy in our department between 1998 and 2003
      who also had gastric biopsies were identified from the surgical pathology files
      and included in the study (n = 3). The location of iron deposition [stromal cells
      (endothelium, fibroblasts, macrophages), glandular epithelium, or extracellular]
      was recorded and subjectively graded as 1+ to 3+ according to the severity of
      deposition within the mucosa. Relevant histologic changes (inflammation, presence
      of H. pylori, ulceration) and clinical features were reviewed. Three patterns of
      GS were identified: A) "nonspecific GS" with predominant iron deposition in the
      stromal cells including macrophages, and focally in epithelium; B) "iron-pill
      gastritis" with often mild gastritis and reactive gastropathy type changes, and
      mostly extracellular deposition with focal stromal cells and epithelial
      deposition; and C) predominant deposition in antral and fundic glandular
      epithelium. Of the 500 cases studied, a total of 18 (3.6%) cases were found to
      have GS. Of these 18 cases, 11 (2.2%) showed pattern A, 4 (0.8%) showed pattern
      B, and 3 (0.6%) showed pattern C. The GS in patterns A and B was always focal or
      patchy (1+ to 2+), whereas in pattern C it was generally diffuse and strong (2+
      to 3+). A history of oral iron medication was present in 2 (n = 11, 0.4%)
      patients with pattern A, in all patients with pattern B (n = 4, 100%), and in
      none of patients with pattern C (n=3, 0%). Varying degrees of mucosal
      inflammation were noted in patients with pattern A cases, and 2 had evidence of
      active Helicobacter pylori infection. Of the 3 cases with known hemochromatosis,
      only one gastric biopsy showed pattern C GS (1+). In conclusion, gastric mucosal
      siderosis is relatively uncommon (3%) but is important to look for as it may lead
      to a diagnosis of hemochromatosis in some cases. Three patterns are recognized:
      A) a "nonspecific" stromal cell predominant pattern, which may be associated with
      gastric inflammation, possibly prior mucosal hemorrhages or iron medications; B)
      extracellular coarse clumps of crystalline iron deposition associated with oral
      iron medications, mild gastritis, and reactive gastropathy type changes ("Iron
      pill gastritis"); and C) gastric glandular siderosis, which may be associated
      with systemic iron overload/hemochromatosis.

PMID- 16625100
TI  - Reticulohistiocytoma (solitary epithelioid histiocytoma): a clinicopathologic and
      immunohistochemical study of 44 cases.
AB  - Reticulohistiocytoma and multicentric reticulohistiocytosis are designations for
      uncommon, incompletely characterized histiocytic proliferations of the skin or
      soft tissues. In this study, we analyzed a uniform group of 44 lesions composed
      of epithelioid histiocytes, comprising a subset of lesions originally designated
      as reticulohistiocytoma, and propose designating them as "solitary epithelioid
      histiocytoma" (SEH), in line with the recently published classification proposal
      for histiocytic disorders. There were 26 males and 18 females with a median age
      of 35 years (range, 2.5-74 years). All patients had a superficial, circumscribed,
      mildly elevated, solitary lesion (size range, 1.5-11 mm; median, 4 mm), located
      in the trunk wall (n = 16), lower extremity (n = 12), head and neck (n = 8,
      including 2 in the oral cavity), upper extremity (n = 6), penis (n = 1), and an
      unspecified site (n = 1). Histologically, the lesions typically involved upper
      and mid-dermis and were not ulcerated. They were composed of large epithelioid
      histiocytes with a varying number of lymphocytes and neutrophils. The histiocytes
      had abundant, typically densely eosinophilic, cytoplasm and mostly mild, if any,
      nuclear atypia. Multinucleated forms with randomly oriented nuclei were also
      present. The histiocytes had low mitotic activity (range, 0-4 mitoses per 10 wide
      HPFs; median, 1 mitosis per 10 HPFs). The lesions contained varying numbers of
      CD3-positive T cells, whereas B lymphocytes, plasma cells, eosinophils, and mast
      cells were scant, if present at all. Immunohistochemically, the epithelioid
      histiocytes were positive for CD163, CD68, lysozyme (variably), and vimentin.
      They often had focal nuclear immunoreactivity for microphthalmia transcription
      factor, and they sometimes had focal reactivity for Factor XIIIa and S-100
      protein. Membrane positivity for CD31, CD43, and CD45 was variable. The
      epithelioid histiocytes were consistently negative for CD3, CD20, CD30, HMB45,
      and keratins. All 12 patients with follow-up information had an uneventful
      clinical course with no recurrences (median, 13 years). SEH is a benign, probably
      reactive, histiocytic proliferation of unknown etiology. It needs to be
      distinguished from Rosai-Dorfman disease, juvenile xanthogranuloma, a variety of
      granulomatous conditions, and some malignant neoplasms, including histiocytic
      sarcoma, melanoma, and epithelioid sarcoma.

PMID- 16625101
TI  - Molecular cytogenetic evidence of t(14;18)(IGH;BCL2) in a substantial proportion
      of primary cutaneous follicle center lymphomas.
AB  - In contrast to nodal follicular lymphoma, limited data exist on genetic changes
      in primary cutaneous follicular lymphoma (primary cutaneous follicle center
      lymphoma according to WHO-EORTC). The detection rate of the BCL2 rearrangement,
      representing the characteristic t(14;18)(q32;q21) underlying follicular lymphoma,
      by polymerase chain reaction (PCR) has been reported to vary over a wide range
      (0%-41%), and only a few cases have been studied by molecular cytogenetic
      techniques such as fluorescence in situ hybridization (FISH). In this study, 27
      primary cutaneous follicle center lymphomas were analyzed by FISH and the results
      compared with those obtained by PCR. FISH demonstrated translocations affecting
      the immunoglobulin heavy chain locus (IGH) in 14 of 27 cases (52%): a
      t(14;18)(q32;q21) involving BCL2 was found in 11 cases (41%), a t(3;14)(q27;q32)
      affecting BCL6 in 2 cases (7%), and in 1 case the partner gene of IGH could not
      be identified. Interestingly, PCR did not detect BCL2 rearrangement in any case.
      These data suggest that the t(14;18)(q32;q21) frequently occurs in primary
      cutaneous follicular lymphoma. The reason(s) why BCL2 rearrangements escape the
      detection by PCR is (are) not clear but could be due to BCL2 mutations,
      breakpoints outside the amplified DNA, or a high load of somatic mutations.

PMID- 16625102
TI  - Recommendations for the supervision of pathology assistants.

PMID- 16625103
TI  - Atypical NK-cell proliferation of the gastrointestinal tract in a patient with
      antigliadin antibodies but not celiac disease.
AB  - We describe a unique case of atypical natural killer (NK)-cell proliferation
      likely related to gluten sensitivity, mimicking NK-cell lymphoma. The patient, a
      32-year-old man, has had persistent multiple erythematous bull-eye lesions in the
      stomach, small bowel, and large bowel for 3 years. Histologically, the lesions
      were well circumscribed and relatively superficial, composed of atypical medium
      sized to large-sized lymphocytes with slightly irregular nuclear contours, a
      dispersed chromatin pattern, and clear cytoplasm. Immunohistochemistry and flow
      cytometry showed that the cells were NK cells expressing CD56 (aberrantly
      bright), T-cell intracellular antigen (TIA)-1, cytoplasmic CD3, and CD94, but not
      surface CD3, with bright aberrant expression of CD7 and a lack of other NK cell
      associated markers. Polymerase chain reaction for rearrangement of the T-cell
      receptor-gamma chain gene showed no evidence of a clonal T-cell population, and
      in situ hybridization for Epstein-Barr virus encoded RNA was negative. There was
      no evidence of the involvement of peripheral blood or bone marrow. Although a
      diagnosis of extranodal NK/T-cell lymphoma was considered because of the atypical
      morphology and immunophenotypic aberrancy, no chemotherapy was given because of
      the relatively superficial nature of the infiltrates, lack of significant
      symptoms, and negativity for Epstein-Barr virus. Two years after initial
      presentation, the patient was found to have high titers of antigliadin antibodies
      with no other evidence of celiac disease. After instituting a gluten-free diet,
      many of the lesions regressed, suggesting that this atypical NK-cell
      proliferation may be driven by an anomalous immune response. Awareness of this
      case may prevent pathologists from misdiagnosing similar lesions as NK/T-cell
      lymphomas. It is as yet unknown whether this process occurs more commonly in
      patients with gluten sensitivity, or in other settings, and the pathogenesis is
      as yet undetermined.

PMID- 16625104
TI  - Angiomyxofibromatous tumor of the falx cerebri.
AB  - We report a distinctive angiomyxofibromatous lesion arising from the falx cerebri
      of a 48-year-old woman. The tumor was composed of bland-appearing, spindle, and
      stellate cells in a myxoid matrix with prominent vascularity. The tumor cells
      were immunopositive diffusely for vimentin and focally for S-100 protein, but
      were immunonegative for epithelial membrane antigen, CD34, MIC2, Bcl-2, glial
      fibrillary acidic protein, cytokeratin CAM 5.2, desmin, and smooth muscle actin.
      This lesion could not be categorized according to the current World Health
      Organization classification of tumors of the nervous system, thus underscoring a
      need to enhance our understanding of myxoid mesenchymal neoplasms and reassess
      their nosology.

PMID- 16625105
TI  - Influence of heart rate and temporal resolution on left-ventricular volumes in
      cardiac multislice spiral computed tomography: a phantom study.
AB  - PURPOSE: We sought to investigate the influence of heart rate and temporal
      resolution on the assessment of left-ventricular (LV) function with multislice
      spiral computed tomography (CT). MATERIAL AND METHODS: A dynamic cardiac phantom
      was repeatedly scanned with a 64-slice CT scanner using a standardized scan
      protocol (64 x 0.6 mm, 120kV, 770mAs(eff), 330 milliseconds rotation time) at
      different simulated heart rates, ranging from 40 to 140 beats per minute. Images
      were reconstructed with an algorithm utilizing data from 1 to 4 cardiac cycles
      (RR intervals). Ejection fraction (EF), end-systolic, end-diastolic, and stroke
      volume as well as cardiac output were calculated. Results of the measurements
      were compared with the real volumes of the phantom. Interscan and intraobserver
      variability were calculated. RESULTS: Using a monosegmental reconstruction
      algorithm, the temporal resolution was fixed to 165 milliseconds. With bi-, tri-,
      and quad-segmental image reconstruction, mean temporal resolution was 128.3 +/-
      33.2 milliseconds, 103.3 +/- 49.2 milliseconds, and 87.8 +/- 81.5 milliseconds,
      respectively. Multisegmental image reconstruction resulted in a lower deviation
      when comparing measured and real volumes. Using mono-, bi-, tri-, and quad
      segmental image reconstruction, the percent deviation between measured and real
      values for EF was 8.2%, 4.5%, 3.3%, and 3.4%, respectively. Applying
      multisegmental image reconstruction with improved temporal resolution the
      deviation decreased with increasing heart rate when compared with mono-segmental
      image reconstruction. Interscan and intraobserver variability for EF were 1.1%
      and 1.9%, respectively. CONCLUSION: Enhanced temporal resolution improves the
      quantification of LV volumes in cardiac multislice spiral CT, enabling reliable
      assessment of LV volumes even at increased heart rates.

PMID- 16625106
TI  - Image quality, motion artifacts, and reconstruction timing of 64-slice coronary
      computed tomography angiography with 0.33-second rotation speed.
AB  - OBJECTIVES: We sought to evaluate the impact of patients' heart rate (HR) on
      coronary CTA image quality (IQ) and motion artifacts using a 64-slice scanner
      with 0.33/360 degrees rotation. MATERIALS AND METHODS: Coronary CTA data sets of
      32 patients (HR <or= 65 beats per minute [bpm], n = 15; HR > 65 bpm to <or=75
      bpm, n = 10; HR > 75 bpm, n = 7) examined on a 64-slice scanner (Sensation 64,
      Siemens Medical Solutions, Forchheim, Germany) with 0.33s/360 degrees gantry
      rotation speed were analyzed. All patients had suspicion of coronary artery
      disease. Data acquisition was performed using 64 x 0.6-mm collimation, and
      contrast enhancement was provided by injection of 80 mL of iopromide (5 mL/s +
      NaCl). Images were reconstructed throughout the RR interval using half-scan and
      dual-segment reconstruction. IQ was rated by 2 observers using a 3-point scale
      from excellent (1) to nondiagnostic (3) for coronary segments. Quality was
      correlated to the HR, time point of optimal IQ analyzed, and the benefit of dual
      segment reconstruction evaluated. RESULTS: Overall mean IQ was 1.31 +/- 0.32 for
      all HR, with IQ being 1.08 +/- 0.12 for HR <or= 65 bpm, 1.62 +/- 0.27 for HR > 65
      bpm <or= 75 bpm and 1.36 +/- 0.31 for HR > 75 bpm (P = 0.0003). Dual-segment
      reconstruction did not significantly improve IQ in any HR group (P = NS). Mean IQ
      was significantly better for LAD than for RCA (P < 0.0001) and LCX (P < 0.01). A
      total of 3.5% (11/318) of coronary artery segments were rated nondiagnostic by at
      least one reader based on motion artifacts. Although in HR < 65 bpm, the best IQ
      was predominately in diastole (93%), in HR > 75 bpm, the best IQ shifted to
      systole in most cases (86%). CONCLUSIONS: Temporal resolution at 0.33-second
      rotation allows for diagnostic IQ within a wide range of HR using half-scan
      reconstruction. With increasing HR the time point of best IQ shifts from mid
      diastole to systole.

PMID- 16625107
TI  - Monitoring of lung motion in patients with malignant pleural mesothelioma using
      two-dimensional and three-dimensional dynamic magnetic resonance imaging:
      comparison with spirometry.
AB  - PURPOSE: To monitor lung motion in patients with malignant pleural mesothelioma
      (MPM) before and after chemotherapy (CHT) using 2-dimensional (2D) and 3
      dimensional (3D) dynamic MRI (dMRI) in comparison with spirometry. METHODS AND
      MATERIALS: Twenty-two patients with MPM were examined before CHT, as well as
      after 3 and 6 CHT cycles (3 months and 6 months) using 2D dMRI (trueFISP; 3
      images/s) and 3D dMRI (FLASH 3D, 1 slab (52 slices)/s) using parallel imaging in
      combination with view-sharing technique. Maximum craniocaudal lung dimensions
      (2D) and lung volumes (3D) were monitored, separated into the tumor-bearing and
      nontumor-bearing hemithorax. Vital capacity (VC) was measured for comparison
      using spirometry. RESULTS: Using 2D technique, there was a significant difference
      between the tumor-bearing and the nontumor-bearing hemithorax before CHT (P <
      0.01) and after 3 CHT cycles (P < 0.05), whereas difference was not significant
      in the second control. In the tumor-bearing hemithorax, mobility increased
      significantly from the status before versus after 3 CHT cycles (4.1 +/- 1.1 cm
      vs. 4.8 +/- 1.4 cm, P < 0.05). Using 3D technique, at maximum inspiration, the
      volume of the tumor-bearing hemithorax was 0.6 +/- 0.4 L and of the nontumor
      bearing hemithorax 1.25 +/- 0.4 L before CHT. In the follow-up exams, these
      volumes changed to 1.05 +/- 0.4 L (P < 0.05) and 1.4 +/- 0.5 L, respectively.
      Using spirometry, there was no significant change in VC (1.9 +/- 0.4 L vs. 2.2 +/
      0.7 L vs. 2.2 +/- 0.9 L). CONCLUSION: dMRI is capable of monitoring changes in
      lung motion and volumetry in patients with MPM not detected by global spirometry.
      Thus, dMRI is proposed for use as a further measure of therapy response.

PMID- 16625108
TI  - Preclinical safety assessment of Vasovist (Gadofosveset trisodium), a new
      magnetic resonance imaging contrast agent for angiography.
AB  - OBJECTIVES: Vasovist (EPIX Pharmaceuticals and Schering AG) is a newly developed
      blood pool contrast agent for magnetic resonance imaging with a high affinity for
      human albumin, making it an ideal tool for the detection of structural
      abnormalities such as stenosis and aneurysm. For the risk assessment of the
      single diagnostic use in patients, the toxicity of this compound was
      investigated. MATERIALS AND METHODS: Studies of acute, repeated-dose,
      reproductive, and developmental toxicity as well as local tolerance,
      immunotoxicity, and mutagenic potential were performed. RESULTS: Lethality was
      observed in rodents after single intravenous administration at doses of at least
      2 orders of magnitude higher than the anticipated human dose of 0.03 mmol/kg. The
      no observed adverse effect level after repeated daily administration over the
      course of 4 weeks to monkeys exceeded the single diagnostic dose by a factor of
      3.3. The main effect of repeated dosing in both rats and monkeys was vacuolation
      in kidney proximal tubules without concomitant effect on kidney function. Studies
      into reproduction toxicity have shown no evidence of effects on fertility or
      perinatal and postnatal development. Signs of embryo-fetal toxicity were observed
      in rabbits after repeated administration of high doses. No indications of
      immunotoxic and mutagenic effects were observed. In local tolerance testing,
      Vasovist was well tolerated after intravenous administration. CONCLUSIONS:
      Vasovist was well tolerated with reasonable safety margins between the single
      diagnostic dose of 0.03 mmol/kg in humans and the doses resulting in adverse
      effects in animal studies.

PMID- 16625109
TI  - Contrast bolus optimization for cardiac 16-slice computed tomography: comparison
      of contrast medium formulations containing 300 and 400 milligrams of iodine per
      milliliter.
AB  - OBJECTIVES: The aims of our study were to compare contrast injection protocols
      with contrast media containing 300 and 400 mg iodine per milliliter for optimal
      contrast enhancement in cardiac multidector row computed tomography (CT) and to
      evaluate the correlation of test bolus curve parameters with the final contrast
      density of the main bolus. MATERIALS AND METHODS: Sixty patients with known or
      suspected coronary artery disease were included in a prospective double-blind
      study. Patients were randomized to 2 groups. Group 1 received 83 mL of a contrast
      medium (CM) containing 300 mg of iodine (Iomeron 300, Bracco Imaging SpA, Milan,
      Italy) at a flow rate of 3.3 mL/s, whereas group 2 received 63 mL of the same
      agent containing 400 mg of iodine (Iomeron 400) at a flow rate of 2.5 mL/s. The
      test bolus volumes were 20 mL and 15 mL, respectively. Imaging was performed
      using a 16-slice CT system (16DCT; Somatom Sensation 16, Siemens Medical
      Solutions, Forchheim, Germany). Contrast densities (Hounsfield Units [HU]) were
      determined in the cardiac chambers and in the main coronary arteries. The peak
      density and area under the curve of the test bolus were calculated for each
      patient. RESULTS: The mean contrast densities of the coronary arteries were 259.1
      +/- 46.7 HU for group 1 and 251.6 +/- 51.0 HU, for group 2. No noteworthy
      differences between groups were noted for density measurements in the cardiac
      chambers or for the ratio of right-to-left ventricle density. Whereas a positive
      correlation was noted for both groups between the area under the curve of the
      test bolus and the mean density of the main bolus, a positive correlation between
      peak density of the test bolus and mean density of the main bolus was noted only
      for group 1. CONCLUSION: Equivalent homogenous enhancement of the ventricular
      cavities and coronary arteries to that obtained using a CM with standard iodine
      concentration (Iomeron 300) can be achieved with lower overall volumes of
      administered CM and reduced injection flow rates when a CM with high iodine
      concentration (Iomeron 400) is used.

PMID- 16625110
TI  - Free-breathing three-dimensional computed tomography of the lung using
      prospective respiratory gating: charge-coupled device camera and laser sensor
      device in an animal experiment.
AB  - PURPOSE: The aim was to investigate the feasibility and image quality of
      prospective respiratory gating for 3-D computed tomography (CT) of the lung.
      MATERIAL AND METHODS: Eight anesthetized pigs underwent prospectively gated
      multidetector computed tomography using 2 devices: a charge-coupled device (CCD)
      camera and a laser sensor. The output signal of both gating devices was connected
      to the scanner instead of ECG unit. Inspiratory and expiratory images were
      obtained during "free-breathing" and analyzed in MPR mode for sharpness of
      bronchi, diaphragm and lung using a 4-point-score (1, excellent to 4, severe
      artifacts). RESULTS: The CCD camera worked in all animals. Using the laser
      sensor, only 50% of expiratory scans could be acquired. All acquired images
      showed excellent sharpness (CCD camera vs. laser sensor) for trachea (1.1 +/- 0.3
      vs. 1.3 +/- 0.5), bronchi (1.4 +/- 0.7 vs. 1.8 +/- 0.6), lung fissures (1.0 vs.
      1.1 +/- 0.3), and lung parenchyma (1.0 +/- 0.2 vs. 1.4 +/- 0.6), and minor to
      major artifacts for diaphragm (1.5 +/- 0.8 vs. 2.0 +/- 1.0, P < 0.05) and
      pericardial lung structures (1.9 +/- 0.7 vs. 2.3 +/- 0.5). CONCLUSION: High image
      quality for inspiratory and expiratory scans was achieved by free-breathing 3-D
      CT of the lung using noncontact prospective respiratory gating.

PMID- 16625111
TI  - Simultaneous cardiac and respiratory synchronization in oxygen-enhanced magnetic
      resonance imaging of the lung using a pneumotachograph for respiratory
      monitoring.
AB  - OBJECTIVES: We sought to evaluate an optimized method for oxygen-enhanced
      magnetic resonance imaging of the lung, using electrocardiogram-trigger and a
      pneumotachograph for simultaneous cardiac and respiratory synchronization.
      MATERIALS AND METHODS: Five series of IR-SSFSE images (echo time = 28.2
      milliseconds; inversion time = 1,200 milliseconds) were obtained in 6 volunteers
      during the ventilation-paradigm room-air/oxygen/room-air: series 1, respiratory
      triggered; series 2, cardiac-triggered; series 3, cardiac-triggered and
      respiratory-synchronized using the signal of the pneumatic belt; series 4,
      cardiac-triggered and respiratory-synchronized using the external signal of the
      pneumotachograph; and series 5, not cardiac-triggered and respiratory
      synchronized using the signal of the pneumotachograph. Standard deviations of the
      lung (SI(var)) and diaphragm mismatch (DM) were measured. The relative SI change
      (DeltaSI) was computed from room-air and oxygen-enhanced images. Parametric maps
      were obtained from cross-correlation analysis of the ventilation paradigm. Mean
      correlation coefficients (cc) and the percentage of activated pixels over the
      lung (Act%) were calculated from these maps. All 5 parameters were compared among
      the 5 series (Friedman-analysis of variance, Dunn's posthoc test). RESULTS: In
      series 4, DM and SI(var) were significantly lower than in respiratory and cardiac
      triggered series (DM = 4.7 vs. 14.3 and 18.4; SI(var) = 4.9 vs. 10 and 11). In
      the same series cc and Act% also were significantly higher than in series 1 and 2
      (cc = 0.86 vs. 0.7 and 0.6; Act% = 71.3 vs. 44.7 and 41.2). DeltaSI was not
      significantly different among all series. CONCLUSIONS: Effective respiratory and
      cardiac synchronization can be achieved in oxygen-enhanced magnetic resonance
      imaging of the lung, using a pneumotachograph for real-time targeting of end
      expiration.

PMID- 16625112
TI  - Quantification of aortic valve calcification using multislice spiral computed
      tomography: comparison with atomic absorption spectroscopy.
AB  - OBJECTIVES: Multislice spiral computed tomography (MSCT) allows the in vivo
      detection of valvular calcification. The aim of this study was to validate the
      quantification of aortic valve calcification (AVC) by MSCT with in vitro
      measurements by atomic absorption spectroscopy. METHODS: In 18 patients with
      severe aortic stenosis, 16 detector row MSCT (SOMATOM Sensation 16, Siemens,
      Forchheim, Germany with scan parameters as follows: 420 milliseconds tube
      rotation time, 12 x 0.75 mm collimation, tube voltage 120 KV) was performed
      before aortic valve replacement. Images were reconstructed at 60% of the RR
      interval with an effective slice thickness of 3 mm and a reconstruction increment
      of 2 mm. AVC was assessed using Agatston AVC score, mass AVC score, and
      volumetric AVC score. After valve replacement, the calcium content of the excised
      human stenotic aortic valves was determined in vitro using atomic absorption
      spectroscopy. RESULTS: The mean Agatston AVC score was 3,842 +/- 1,790, the mean
      volumetric AVC score was 3,061 +/- 1,406, and mass AVC score was 888 +/- 492 as
      quantified by MSCT. Atomic absorption spectroscopy showed a mean true
      calcification mass (Ca5(PO4)3OH) of 19 +/- 8 mass%. There was a significant
      correlation between in vivo AVC scores determined by MSCT and in vitro mean true
      calcification mass (r = 0.74, P = 0.0004 for mass AVC score, r = 0.79, P = 0.0001
      for volumetric AVC score and r = 0.80, P = 0.0001 for Agatston AVC score)
      determined by atomic absorption spectroscopy. Linear regression analysis showed a
      significant association between the degree of hydroxyapatite (given in mass%) in
      the aortic valve and the degree of AVC (R = 0.74, F = 19.6, P = 0.0004 for mass
      AVC score, R = 0.80, F = 29.3, P = 0.0001 for Agatston AVC score and R = 0.79, F
      = 27.3, P = 0.0001 for volumetric AVC score) assessed by MSCT. CONCLUSION: MSCT
      allows accurate in vivo quantification of aortic valve calcifications.

PMID- 16625113
TI  - Commercial human albumin preparations for clinical use are immunosuppressive in
      vitro.
AB  - OBJECTIVE: We previously reported significant variations in oxidation status and
      molecular length among sources and lots of human serum albumin (HSA) commercial
      preparations intended for clinical use. In this report, we investigated what
      effect the presence of HSA products have on the immune response in vitro. DESIGN:
      Laboratory study. SETTING: Trauma research basic science laboratory. SUBJECTS:
      Activated human peripheral blood mononuclear cells. INTERVENTIONS: Six commercial
      HSA preparations were tested for their effect on cytokine release from activated
      human peripheral blood mononuclear cells (PBMCs) and T-lymphocytes. Mass
      spectrometry analysis of aspartyl-alanyl diketopiperazine (DA-DKP) content of HSA
      and percentage of HSA having lost its amino terminal dipeptide aspartyl alanyl
      (HSA-DA) were correlated. MEASUREMENTS AND MAIN RESULTS: Human PBMCs were
      cultured in the presence of six commercial HSA preparations and activated via the
      T-cell receptor complex. A cloned T-lymphocyte cell line, activated with specific
      antigen, was also cultured with both synthetic DA-DKP and small molecular weight
      extracts from the commercial HSA tested. Supernatants were quantified by enzyme
      linked immunosorbent assay for interferon-gamma and tumor necrosis factor-alpha
      content. DA-DKP was extracted from HSA by centrifugal filters and quantified by
      anion exchange liquid chromatography coupled to negative electrospray ionization
      mass spectrometry. HSA species were determined by reverse phase liquid
      chromatography coupled to positive electrospray ionization, time of flight mass
      spectrometry. All HSA preparations significantly inhibited the in vitro
      production of interferon-gamma and tumor necrosis factor-alpha by activated
      PBMCs. DA-DKP was detected in all HSA sources at concentrations ranging between
      42.0 and 79.6 microM. A synthetic form of DA-DKP possessed similar
      immunosuppressive qualities in a dose-dependent manner on T lymphocytes.
      CONCLUSIONS: DA-DKP was present in significant concentrations in all HSA sources
      tested and was partially responsible for the immunosuppressive effects of HSA on
      activated PBMCs and T-lymphocytes in vitro. In view of these findings,
      administering HSA to immunocompromised critically ill patients might be
      reevaluated.

PMID- 16625114
TI  - Local activation of the tissue factor-factor VIIa pathway in patients with
      pneumonia and the effect of inhibition of this pathway in murine pneumococcal
      pneumonia.
AB  - OBJECTIVE: The tissue factor (TF)-factor VIIa (FVIIa) complex not only is
      essential for activation of blood coagulation but also affect the inflammatory
      response during sepsis. The objective of this study was to determine the role of
      TF-FVIIa in pneumonia caused by Streptococcus pneumoniae, the most important
      causative organism in community-acquired pneumonia and a major cause of sepsis.
      DESIGN: A controlled, in vivo laboratory study. SETTING: Research laboratory of a
      health sciences university. PATIENTS AND SUBJECTS: Patients with unilateral
      community-acquired pneumonia and female BALB/c mice. INTERVENTIONS: Bilateral
      bronchoalveolar lavage was performed in patients with community-acquired
      pneumonia. In mice, pneumonia was induced by intranasal inoculation with S.
      pneumoniae with or without concurrent inhibition of TF-FVIIa by subcutaneous
      injections of recombinant nematode anticoagulant protein (rNAPc2). MEASUREMENTS
      AND MAIN RESULTS: Patients with unilateral community-acquired pneumonia
      demonstrated elevated concentrations of FVIIa, soluble TF, and thrombin
      antithrombin complexes in bronchoalveolar lavage fluid obtained from the infected
      site compared with the uninfected site. Mice with S. pneumoniae pneumonia
      displayed increased TF expression and fibrin deposits in lungs together with
      elevated thrombin-antithrombin complex levels in bronchoalveolar lavage fluid;
      inhibition of TF-FVIIa by rNAPc2 attenuated the procoagulant response in the lung
      but did not affect host defense, as reflected by an unaltered outgrowth of
      pneumococci and an unchanged survival. CONCLUSIONS: These data suggest that TF
      FVIIa activity contributes to activation of coagulation in the lung during
      pneumococcal pneumonia but does not play an important role in the antibacterial
      host defense in this murine model.

PMID- 16625115
TI  - In-house, overnight physician staffing: a cross-sectional survey of Canadian
      adult and pediatric intensive care units.
AB  - OBJECTIVE: Physician staffing is an important determinant of patient outcomes
      following intensive care unit (ICU) admission. We conducted a national survey of
      in-house after-hours physician staffing in Canadian ICUs. DESIGN: : Cross
      sectional survey. SETTING: Canadian adult and pediatric ICUs. PARTICIPANTS: ICU
      directors. INTERVENTIONS: ICU directors of Canadian adult and pediatric ICUs were
      surveyed to describe overnight staffing by interns, residents, critical care
      medicine trainees, clinical assistants, and ICU physicians in their ICUs.
      MEASUREMENTS AND MAIN RESULTS: Data were collected regarding hospital and ICU
      demographics and ICU staffing. For ICUs with in-house overnight physicians, we
      documented physician experience, shift duration, and clinical responsibilities
      outside the ICU. We identified 98 Canadian ICU directors, of whom 88 (90%)
      responded. Dedicated in-house physician coverage overnight was reported in 53
      (60%) ICUs, including 13 (15%) in which ICU staff physicians stayed in-house
      overnight. Compared with ICUs without in-house physicians, those with in-house
      physicians had more ICU beds (15 vs. 8.5, p=.0001) and fewer ICU staff physicians
      (5 vs. 7, p=.03). For the 271 physicians who provide overnight staffing, the
      median level of postgraduate experience was 3 yrs (range, <1 yr, >10 yrs); 129
      (48%) had <3 months of ICU experience. Most shifts (83%) were >20 hrs long.
      CONCLUSIONS: In-house overnight physician staffing in Canadian ICUs varies
      widely. Only a minority of ICUs comply with the 2003 Society of Critical Care
      Medicine guidelines for adult ICUs recommending continuous in-house staffing by
      ICU staff physicians. The duration of most ICU shifts raises concern about
      workload-associated fatigue and medical error. The impact of current nighttime
      staffing requires further evaluation with respect to patient outcomes.

PMID- 16625116
TI  - Effects of partial ventilatory support modalities on respiratory function in
      severe hypoxemic lung injury.
AB  - OBJECTIVE: The early phase of acute respiratory distress syndrome (ARDS) is
      characterized by impaired respiratory mechanics, ventilation-perfusion mismatch,
      and severe hypoxemia. Partial ventilatory support can effectively unload the
      respiratory workload and improve pulmonary gas exchange with less hemodynamic
      compromise. The partial ventilatory support mode most indicated in early phases
      of ARDS has not been determined. This study compares the effects of assisted
      ventilatory techniques on breathing pattern, gas exchange, hemodynamic function,
      and respiratory effort with those of controlled mechanical ventilation in
      similarly sedated subjects. DESIGN: Prospectively randomized crossover animal
      study. SETTING: Animal research laboratory. SUBJECTS: Eleven anesthetized and
      mechanically ventilated pigs. INTERVENTIONS: Acute lung injury was induced by
      lung lavage. Pressure-controlled ventilation (PCV), pressure-controlled assisted
      ventilation (P-ACV), bilevel positive airway pressure (BIPAP), and pressure
      support ventilation (PSV) with equal airway pressures and sedation were applied
      in random order. MEASUREMENTS AND MAIN RESULTS: Gas exchange, respiratory effort,
      and hemodynamic function were measured, and ventilation-perfusion distributions
      were calculated by multiple inert-gas-elimination techniques. The results
      revealed that partial ventilatory support was superior to PCV in maintaining
      adequate oxygenation and hemodynamic function with reduced sedation. The effects
      of P-ACV, BIPAP, and PSV were comparable with respect to gas exchange and
      hemodynamic function, except for a more pronounced reduction in shunt during
      BIPAP. P-ACV and PSV were superior to BIPAP to reduce respiratory drive and work
      of breathing. PSV affected the pattern of breathing and deadspace to a greater
      degree than did P-ACV. CONCLUSIONS: In acute lung injury, P-ACV preserves
      oxygenation and hemodynamic function with less respiratory effort compared with
      BIPAP and reduces the need for sedation compared with PCV.

PMID- 16625117
TI  - Hypertonic saline enhances host defense to bacterial challenge by augmenting Toll
      like receptors.
AB  - OBJECTIVE: To determine whether hypertonic saline infusion modulates thermal
      injury-induced bacterial translocation and host response to bacterial challenge
      through the augmentation of Toll-like receptors (TLRs). DESIGN: Prospective,
      experimental study. SETTING: Research laboratory at a university hospital.
      SUBJECTS: Thermal injury models in the mice. INTERVENTIONS: In experiment 1, mice
      underwent burn were given with 10 mL/kg hypertonic saline (7.5% NaCl), 10 mg/kg
      saline (N/S1), or 80 mL/kg saline (N/S2) at 4 or 8 hrs after burn. At 24 hrs
      after burn, mesenteric lymph nodes were harvested for bacterial translocation
      assay. In experiment 2, mice receiving hypertonic saline or saline after thermal
      injury received peritoneal challenge with Escherichia coli, and bacterial
      clearance was measured. In experiment 3, peritoneal cells from mice receiving
      hypertonic saline or saline after thermal injury were incubated with E. coli, and
      bacterial count, TLR2, TLR4, MIP2, CXCR2, pp38, and ERK expression were
      evaluated. In experiment 4, reactive oxygen species production, CXCR2, MIP2,
      TLR2, and TLR4 expression of bone marrow neutrophil from mice receiving
      hypertonic saline or saline treatment after thermal injury were evaluated. In
      experiment 5, neutrophil were cultured with hypertonic saline or N/S and
      incubated with E. coli. TLR2 and TLR4 expression and bacterial count were
      evaluated. In experiment 6, mice were fed with oral antibiotics with or without
      lipopolysaccharide, a TLR ligand, supplements. At 24 hrs after burn, mesenteric
      lymph nodes were harvested for bacterial translocation assay, and neutrophils
      were harvested for TLR2 and TLR4 protein assay. MEASUREMENTS AND MAIN RESULTS:
      Hypertonic saline decreased thermal injury-induced bacterial translocation.
      Hypertonic saline increased bacterial clearance, phagocytic activity, and TLR2,
      TLR4, CXCR2, pp38, and p44/42 expression of peritoneal cells. Hypertonic saline
      treatment at 4 or 8 hrs after thermal injury decreased reactive oxygen species
      production of neutrophil. Hypertonic saline injection increased TLR2, TLR4, and
      pp38 expression of neutrophil. In vitro treatment of neutrophil with hypertonic
      saline increased phagocytic activity and TLR2 and TLR4 expression. Commensal
      depletion with oral antibiotics decreased TLR2 and TLR4 expression of neutrophil;
      lipopolysaccharide increased TLR4 expression of neutrophil and decreased thermal
      injury-induced bacterial translocation. CONCLUSIONS: Restoration of extracellular
      fluid in burn shock with hypertonic saline decreased thermal injury-induced
      bacterial translocation. Hypertonic saline increased the phagocytic activity and
      TLR2, TLR4, CXCR2, pp38, and P44/42 expression of peritoneal cells. Hypertonic
      saline decreased reactive oxygen species but increased TLR2, TLR4, and pp38
      expression and phagocytic activity of bone marrow neutrophil. Stimulation of the
      TLRs with lipopolysaccharide in commensal depleted mice increased TLRs expression
      of neutrophil and decreased thermal injury-induced bacterial translocation. Taken
      together with the fact that stimulation of TLRs with hypertonic saline increases
      phagocytic activity of systemic inflammatory cells, we conclude that TLRs play a
      critical role in the innate immunity by recognizing bacteria and that hypertonic
      saline enhances host response to bacterial challenge by increasing TLRs of
      inflammatory cells.

PMID- 16625118
TI  - Hypertonic saline resuscitation prevents hydrostatically induced intestinal edema
      and ileus.
AB  - OBJECTIVE: We have shown that acute edema induced by mesenteric venous
      hypertension (MV-HTN) impairs intestinal transit and reduces the standardized
      engineering measures of intestinal stiffness (elastic modulus) and residual
      stress (opening angle). We hypothesized that hypertonic saline (7.5%) would
      reverse these detrimental effects of acute edema. DESIGN: Laboratory study.
      SETTING: University laboratory. SUBJECTS: Male Sprague Dawley rats (270-330 g).
      INTERVENTIONS: Rats were randomized to five groups: sham, MV-HTN alone, MV-HTN
      with 4 mL/kg normal saline resuscitation (equal volume), MV-HTN with 33 mL/kg
      normal saline resuscitation (equal salt), and MV-HTN with 4 mL/kg hypertonic
      saline. Intestinal edema was measured by wet to dry tissue weight ratio. A
      duodenal catheter was placed and, 30 mins before death, fluorescein
      isothiocyanate Dextran was injected. At death, dye concentrations were measured
      to determine intestinal transit. Segments of distal ileum were hung to a fixed
      point in a tissue bath and to a force displacement transducer and stretched in
      increments of 1 mm; we recorded the new length and the corresponding force from
      the force displacement transducer to determine elastic modulus. Next, two
      transverse cuts were made yielding a 1- to 2-mm thick ring-shaped segment of
      tissue which was then cut radially to open the ring. Then the opening angle was
      measured. MEASUREMENTS AND MAIN RESULTS: MV-HTN, MV-HTN with 4 mL/kg normal
      saline, and MV-HTN with 33 mL/kg normal saline caused a significant increase in
      tissue edema and a significant decrease in intestinal transit, stiffness, and
      residual stress compared with sham. Hypertonic saline significantly lessened the
      effect of edema on intestinal transit and prevented the changes in stiffness and
      residual stress. CONCLUSIONS: Hypertonic saline prevented intestinal tissue
      edema. In addition, hypertonic saline improved intestinal transit, possibly
      through more efficient transmission of muscle force through stiffer intestinal
      tissue.

PMID- 16625119
TI  - Effects of vasopressin, norepinephrine, and L-arginine on intestinal
      microcirculation in endotoxemia.
AB  - OBJECTIVE: The effects of vasopressin, norepinephrine, and L-arginine alone or
      combined on intestinal microcirculation were evaluated in the septic mouse by
      intravital microscopy, with which we measured the erythrocyte flux and velocity
      in villus tip arterioles and the density of perfused villi. DESIGN: Controlled
      animal study. SETTING: University research laboratory. SUBJECTS: Female BALB/c
      mice weighing between 18 and 21 g. INTERVENTIONS: Anesthetized and ventilated
      mice received at t0 an intravenous injection of Escherichia coli endotoxin (2
      mg/kg bolus intravenously), inducing after 1 hr (t60) a decrease in mean arterial
      blood pressure to 40-50 mm Hg associated with a significant decrease in
      erythrocyte flux and velocity in villus tip arterioles and in the density of
      perfused villi. The mice then received a randomly different treatment for
      endotoxin-induced shock. Treatments consisted in continuous intravenous infusion
      for 1 hr with either saline (control group), norepinephrine, vasopressin, L
      arginine, vasopressin+L-arginine, or norepinephrine+L-arginine. The doses of
      vasopressors (used alone or combined with L-arginine) were titrated to restore
      mean arterial pressure to the baseline level. MEASUREMENTS AND MAIN RESULTS: At
      the end of the treatment (t120), we observed in the control group further
      decreases in arteriolar flux and velocity and in the density of perfused villi.
      In the groups treated by a vasopressor alone, mean arterial pressure returned to
      baseline and there were no additional decreases in arteriolar flux and velocity
      or in the density of perfused villi. However, these latter three variables did
      not return to their preshock baseline values. Even though L-arginine did not
      restore mean arterial pressure, the infusion of L-arginine alone prevented the
      decrease in flux or erythrocyte velocity occurring between t60 and t120 and
      conserved to some extent the density of perfused villi compared with that in the
      control groups. In addition, we found that simultaneous administration of
      norepinephrine or vasopressin with L-arginine improved all microcirculation
      variables more efficiently than either vasopressor alone. CONCLUSIONS: From these
      data, we conclude that a) restoring mean arterial pressure after 1 hr of
      endotoxemia was not sufficient to restore ad integrum intestinal mucosa
      microvascular perfusion; b) L-arginine could have a beneficial effect at the
      microcirculatory level, which was independent of mean arterial pressure; and c)
      administration of L-arginine combined with the maintenance of perfusion pressure
      by vasopressive drugs allowed a better preservation of intestinal
      microcirculation at an early stage of endotoxemia.

PMID- 16625120
TI  - Effect of hydroxyethyl starch on vascular leak syndrome and neutrophil
      accumulation during hypoxia.
AB  - OBJECTIVE: Several studies have suggested that intravenous hydroxyethyl starch
      treatment may dampen acute inflammatory responses. It is well documented that
      limited oxygen delivery to tissues (hypoxia) is common in acute inflammation, and
      numerous parallels exist between acute responses to hypoxia and to inflammation,
      including the observation that both are associated with increased vascular
      leakage and neutrophil infiltration of tissues. Therefore, we compared functional
      influences of hydroxyethyl starch on normoxic or posthypoxic endothelia. DESIGN:
      Laboratory study. SETTING: University hospital. SUBJECTS: Cultured human
      microvascular endothelial cells and mice (C57BL/6/129 svj). INTERVENTIONS: We
      measured functional influences of hydroxyethyl starch on normoxic or posthypoxic
      endothelia. MEASUREMENTS AND MAIN RESULTS: Studies to assess endothelial barrier
      function in vitro indicated that the addition of hydroxyethyl starch promotes
      endothelial barrier in a dose-dependent fashion and hydroxyethyl starch-barrier
      effects are increased following endothelial hypoxia exposure (human microvascular
      endothelial cells, 48 hrs, 2% oxygen). Treatment of human microvascular
      endothelial cells with hydroxyethyl starch resulted in a dose-dependent increase
      in 157-phosphorylated vasodilator-stimulated phosphoprotein, a protein
      responsible for controlling the geometry of actin-filaments. Neutrophil adhesion
      was decreased in the presence of physiologically relevant concentrations of
      hydroxyethyl starch in vitro, particularly after endothelial hypoxia exposure.
      Using a murine model of normobaric hypoxia, increases in vascular leakage and
      pulmonary edema associated with hypoxia exposure (4 hrs at 8% oxygen) were
      decreased in animals treated with intravenous hydroxyethyl starch. Increases of
      tissue neutrophil accumulation following hypoxia exposure were dampened in
      hydroxyethyl starch-treated mice. CONCLUSIONS: Taken together, these results
      indicate that hypoxia-induced increases in vascular leakage and acute
      inflammation are attenuated by hydroxyethyl starch treatment.

PMID- 16625121
TI  - Effects of endothelin receptor antagonism on acute lung injury induced by
      chlorine gas.
AB  - OBJECTIVE: To test the hypothesis that the endothelin system is involved in
      chlorine gas-induced lung injury. DESIGN: Experimental study. SETTING: Academic
      research laboratory. SUBJECTS: Twenty-four domestic juvenile pigs. INTERVENTIONS:
      Anesthetized, ventilated pigs were exposed to chlorine gas (400 parts per million
      in air) for 20 mins and then randomly allocated to four groups (n=6 in each
      group). The tezosentan pretreatment group received the dual endothelin receptor
      antagonist tezosentan 20 mins before and hyperoxic gas (Fio2 0.6) after chlorine
      gas exposure. The tezosentan postinjury treatment group received hyperoxic gas
      after chlorine gas exposure and tezosentan 60 mins later. Animals in the oxygen
      group received hyperoxic gas after chlorine gas exposure. Pigs in the fourth
      group (air) were ventilated with room air (Fio2 0.21) throughout the experiment.
      MEASUREMENTS AND MAIN RESULTS: Hemodynamics, gas exchange, lung mechanics, and
      plasma endothelin-1 were evaluated for 6 hrs. Chlorine gas exposure induced an
      increase in circulating endothelin-1 by 90% (p<.05). The acute chlorine gas
      induced rise in pulmonary vascular resistance was partly blocked by tezosentan
      pretreatment (p<.001). Tezosentan postinjury treatment also decreased pulmonary
      vascular resistance to levels significantly lower than in the air and oxygen
      groups (p<.001). Recovery of peak airway pressure was better in the tezosentan
      treated groups than in the air group. There were significant linear relationships
      between circulating endothelin-1 and pulmonary vascular resistance (r=.47,
      p<.001) and endothelin-1 and peak airway pressure (r=.41, p<.001). These
      relationships were modified by tezosentan. CONCLUSIONS: Tezosentan modified
      chlorine gas-induced pulmonary dysfunction, indicating that the endothelin system
      is involved in this mode of acute lung injury.

PMID- 16625122
TI  - Rib fractures: relationship with pneumonia and mortality.
AB  - OBJECTIVE: In single-institution studies, age is a risk factor for mortality
      after rib fracture. Sample size has limited the assessment of other risk factors.
      We used a national database to analyze suspected risk factors contributing to
      pneumonia and mortality in patients sustaining rib fractures. DESIGN: : Database
      analysis. PATIENTS: All patients with rib fractures discharged from hospitals
      submitting information to the Nationwide Inpatient Sample database.
      INTERVENTIONS: The 1999 Nationwide Inpatient Sample was queried for all patients
      with rib fracture. Age, gender, number of rib fractures, Injury Severity Score,
      comorbidities, pneumonia, and mortality were abstracted from the database.
      Comorbidities were scored according to Elixhauser. Multivariate analysis
      identified independent risk factors for mortality and pneumonia. MEASUREMENTS AND
      MAIN RESULTS: We identified 23,426 patients; 17,308 patients had a primary
      diagnosis of trauma and were included in the analysis. Mean age was 56. Mean
      Injury Severity Score was 13.1. The number of comorbidities ranged from 0 to 9.
      Overall mortality was 4%. Six percent of patients had pneumonia. In a
      multivariate model, age and Injury Severity Score were significantly associated
      with both mortality and pneumonia. Comorbidity score was associated with
      pneumonia and mortality only in patients with isolated thoracic trauma. Pneumonia
      was associated with mortality only in patients with isolated thoracic trauma.
      CONCLUSIONS: In a model controlling for multiple known risk factors, age and
      Injury Severity Score were the only important predictors of mortality in patients
      with rib fractures and multiple-system injury. Pneumonia was significantly
      associated with mortality only in patients with isolated thoracic trauma.

PMID- 16625123
TI  - The future of our specialty: critical care medicine a decade from now.

PMID- 16625124
TI  - Does microalbuminuria predict illness severity in critically ill patients on the
      intensive care unit? A systematic review.
AB  - CONTEXT: Studies assessing the accuracy of microalbuminuria to predict illness
      severity on the intensive care unit have produced inconsistent results.
      OBJECTIVE: To determine the diagnostic accuracy of microalbuminuria to predict
      illness severity in critically ill patients on the intensive care unit. DATA
      SOURCE: MEDLINE (1951 to September 2004) and EMBASE (1980 to September 2004)
      electronic databases were searched for relevant studies. Reference lists of all
      abstracts were manually searched to identify studies not included in the
      electronic database. STUDY SELECTION: Studies that prospectively evaluated the
      accuracy of microalbuminuria to predict illness severity and/or mortality
      probability in adult patients on the intensive care unit were selected. DATA
      EXTRACTION: We included nine studies in the review. Data to evaluate
      methodological quality and results were abstracted. DATA SYNTHESIS: The
      methodological quality of a number of studies was poor. Significant heterogeneity
      in the design and conduct of the studies circumvented the data being subjected to
      meta-analysis. Studies also differed in the timing of the index test, in the
      methods of quantifying microalbuminuria, and in the cutoff values used.
      CONCLUSIONS: This descriptive analysis reveals that microalbuminuria may hold
      promise as a predictor of illness severity and mortality on the intensive care
      unit. However, future epidemiologic studies need to be conducted to determine the
      optimal timing as well as the threshold reference value for the urine albumin
      creatinine ratio in the adult intensive care unit population. Thereafter,
      multiple-center prospective epidemiologic studies must be conducted to confirm
      and validate the findings of these preliminary studies. Future studies should
      conform to the Standards for Reporting of Diagnostic Accuracy checklist in terms
      of study design, conduct, and reporting. Presently there is no evidence to
      warrant the use of this tool on the intensive care unit.

PMID- 16625125
TI  - Duration of hypotension before initiation of effective antimicrobial therapy is
      the critical determinant of survival in human septic shock.
AB  - OBJECTIVE: To determine the prevalence and impact on mortality of delays in
      initiation of effective antimicrobial therapy from initial onset of
      recurrent/persistent hypotension of septic shock. DESIGN: A retrospective cohort
      study performed between July 1989 and June 2004. SETTING: Fourteen intensive care
      units (four medical, four surgical, six mixed medical/surgical) and ten hospitals
      (four academic, six community) in Canada and the United States. PATIENTS: Medical
      records of 2,731 adult patients with septic shock. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The main outcome measure was survival to hospital
      discharge. Among the 2,154 septic shock patients (78.9% total) who received
      effective antimicrobial therapy only after the onset of recurrent or persistent
      hypotension, a strong relationship between the delay in effective antimicrobial
      initiation and in-hospital mortality was noted (adjusted odds ratio 1.119 [per
      hour delay], 95% confidence interval 1.103-1.136, p<.0001). Administration of an
      antimicrobial effective for isolated or suspected pathogens within the first hour
      of documented hypotension was associated with a survival rate of 79.9%. Each hour
      of delay in antimicrobial administration over the ensuing 6 hrs was associated
      with an average decrease in survival of 7.6%. By the second hour after onset of
      persistent/recurrent hypotension, in-hospital mortality rate was significantly
      increased relative to receiving therapy within the first hour (odds ratio 1.67;
      95% confidence interval, 1.12-2.48). In multivariate analysis (including Acute
      Physiology and Chronic Health Evaluation II score and therapeutic variables),
      time to initiation of effective antimicrobial therapy was the single strongest
      predictor of outcome. Median time to effective antimicrobial therapy was 6 hrs
      (25-75th percentile, 2.0-15.0 hrs). CONCLUSIONS: Effective antimicrobial
      administration within the first hour of documented hypotension was associated
      with increased survival to hospital discharge in adult patients with septic
      shock. Despite a progressive increase in mortality rate with increasing delays,
      only 50% of septic shock patients received effective antimicrobial therapy within
      6 hrs of documented hypotension.

PMID- 16625126
TI  - Organizational climate and intensive care unit nurses' intention to leave.
AB  - OBJECTIVE: The purposes of this study were to a) estimate the incidence of
      intensive care units nurses' intention to leave due to working conditions; and b)
      identify factors predicting this phenomenon. DESIGN: Cross-sectional design.
      SETTING: Hospitals and critical care units. SUBJECTS: Registered nurses (RNs)
      employed in adult intensive care units. INTERVENTIONS: Organizational climate,
      nurse demographics, intention to leave, and reason for intending to leave were
      collected using a self-report survey. MEASUREMENTS AND MAIN RESULTS: Nurses were
      categorized into two groups: a) those intending to leave due to working
      conditions; and b) others (e.g., those not leaving or retirees). The measure of
      organizational climate had seven subscales: professional practice,
      staffing/resource adequacy, nurse management, nursing process, nurse/physician
      collaboration, nurse competence, and positive scheduling climate. Setting
      characteristics came from American Hospital Association data and a survey of
      chief nursing officers. RESULTS: A total of 2,323 RNs from 66 hospitals and 110
      critical care units were surveyed across the nation. On average, the RN was 39.5
      yrs old (SD = 9.40), had 15.6 yrs (SD = 9.20) experience in health care, and had
      worked in his or her current position for 8.0 yrs (SD = 7.50). Seventeen percent
      (n = 391) of the respondents indicated intending to leave their position in the
      coming year. Of those, 52% (n = 202) reported that the reason was due to working
      conditions. Organizational climate factors that had an independent effect on
      intensive care unit nurse intention to leave due to working conditions were
      professional practice, nurse competence, and tenure (p < .05). CONCLUSIONS:
      Improving professional practice in the work environment and clinical competence
      of the nurses as well as supporting new hires may reduce turnover and help ensure
      a stable and qualified workforce.

PMID- 16625127
TI  - The relationship between sedative infusion requirements and permissive
      hypercapnia in critically ill, mechanically ventilated patients.
AB  - OBJECTIVE: Permissive hypercapnia (PH) may result from mechanical ventilation
      (MV) strategies that intentionally reduce minute ventilation. Sedative doses
      required to tolerate PH have not been well characterized. With increased
      attention to lung-protective ventilation, characterization of sedative
      requirements with PH and determination of sedative dose changes with PH are
      needed. DESIGN: Retrospective analysis. SETTING: Tertiary care university
      hospital. PATIENTS: We evaluated 124 patients randomized in a previous study to
      either propofol or midazolam. PH was employed in ten of 60 patients receiving
      propofol and 13 of 64 patients receiving midazolam. INTERVENTIONS: We analyzed
      dosing of propofol and midazolam in patients undergoing PH through a
      retrospective analysis of an existing database on MV patients. Total sedative
      (propofol and midazolam) dose was recorded for the first three days of MV. Linear
      regression analysis (dependent variable: sedative dose) was used to analyze the
      following independent variables: PH, age, gender, daily sedative interruption,
      type of respiratory failure, presence of hepatic and/or renal failure, Acute
      Physiology and Chronic Health Evaluation II score, morphine dose, and Ramsay
      sedation score. MEASUREMENTS AND MAIN RESULTS: Propofol dose was higher in PH
      patients (42.5+/-16.2 vs. 27.0+/-15.3; p=.02); Midazolam dose did not differ
      between PH and non-PH patients (0.05 [0.04, 0.14] vs. 0.05 [0.03, 0.07]; p=.17).
      By univariate linear regression analysis, propofol dose was significantly
      dependent on PH, age, type of respiratory failure, morphine dose, and Ramsay
      score, with PH (regression coefficient, 11.7; 95% confidence interval, 1.2-22.7;
      p=.03) and age (regression coefficient, -0.3; 95% confidence interval -0.5 to 
      0.08; p=.005) remaining significant by multivariate linear regression. By
      univariate linear regression analysis, midazolam dose was dependent on age,
      morphine dose, and Ramsay score, but not PH; only morphine dose (regression
      coefficient, 0.44; 95% confidence interval, 0.22-0.67 for a 0.1-unit increase in
      morphine dose; p<.001) was significant by multivariate linear regression.
      CONCLUSIONS: We conclude that higher doses of propofol but not midazolam are
      required to sedate patients managed with PH.

PMID- 16625128
TI  - Do-not-resuscitate decisions in six European countries.
AB  - OBJECTIVE: To study and compare the incidence and main background characteristics
      of do-not-resuscitate (DNR) decision making in six European countries. DESIGN:
      Retrospective. SETTING: We studied DNR decisions simultaneously in Belgium
      (Flanders), Denmark, Italy (four regions), the Netherlands, Sweden, and
      Switzerland (German-speaking part). In each country, random samples of death
      certificates were drawn from death registries to which all deaths are reported.
      The deaths occurred between June 2001 and February 2002. PARTICIPANTS: Reporting
      physicians received a mailed questionnaire about the medical decision making that
      had preceded death. The response percentage was 75% for the Netherlands, 67% for
      Switzerland, 62% for Denmark, 61% for Sweden, 59% for Belgium, and 44% for Italy.
      The total number of deaths studied was 20,480. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Measurements were frequency of DNR decisions, both individual
      and institutional, and patient involvement. Before death, an individual DNR
      decision was made in about 50-60% of all nonsudden deaths (Switzerland 73%, Italy
      16%). The frequency of institutional decisions was highest in Sweden (22%) and
      Italy (17%) and lowest in Belgium (5%). DNR decisions are discussed with
      competent patients in 10-84% of cases. In the Netherlands patient involvement
      rose from 53% in 1990 to 84% in 2001. In case of incompetent patients, physicians
      bypassed relatives in 5-37% of cases. CONCLUSIONS: Except in Italy, DNR decisions
      are a common phenomenon in these six countries. Most of these decisions are
      individual, but institutional decisions occur frequently as well. In most
      countries, the involvement of patients in DNR decision making can be improved.

PMID- 16625129
TI  - Extravascular lung water determined with single transpulmonary thermodilution
      correlates with the severity of sepsis-induced acute lung injury.
AB  - OBJECTIVE: To find out if the extravascular lung water index (EVLWI) and the
      derived permeability indexes determined by the single transpulmonary
      thermodilution technique are associated with markers of acute lung injury in
      human septic shock. DESIGN: Prospective, observational study. SETTING: Mixed
      intensive care unit of a 900-bed university hospital. PATIENTS: Thirty-eight
      consecutive adult patients with septic shock and acute lung injury.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The variables were assessed
      over a 72-hr period and included hemodynamics, EVLWI, and pulmonary vascular
      permeability indexes determined with the single indicator transpulmonary
      thermodilution technique, lung compliance, oxygenation ratio (Pao2/Fio2), lung
      injury score, cell counts, and the plasma concentration of endothelin-1. At day
      1, EVLWI was elevated (>or=7 mL/kg) in 28 (74%) patients and correlated with lung
      compliance (r=-.48, p=.002), Pao2/Fio2 (r=-.50, p=.001), lung injury score
      (r=.46, p=.004), roentgenogram quadrants (r=.39, p=.02), and platelet count (r=
      .43, p=.007). At day 3, EVLWI correlated with compliance (r=-.51, p=.002),
      Pao2/Fio2 (r=-.49, p = .006), and lung injury score (r=.53, p=.003). At day 3,
      EVLWI and pulmonary vascular permeability indexes were higher in nonsurvivors
      (p<.05). The plasma concentration of endothelin-1 (mean+/-sd) was significantly
      higher in patients with elevated EVLWI (>or=7 mL/kg) (3.85+/-1.40 vs. 2.07+/-0.38
      pg/mL, respectively). Twenty-two (59%) patients died before day 28. CONCLUSIONS:
      In human septic shock, EVLWI demonstrated moderate correlation with markers of
      acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram
      quadrants, and lung injury score. In nonsurvivors, EVLWI and permeability indexes
      were significantly increased at day 3. Thus, EVLWI might be of value as an
      indicator of prognosis and severity of sepsis-induced acute lung injury.

PMID- 16625130
TI  - Functional residual capacity measurement by heptafluoropropane in ventilated
      newborn lungs: in vitro and in vivo validation.
AB  - OBJECTIVE: Heptafluoropropane is an inert gas commercially used as propellant for
      inhalers. Since heptafluoropropane can be detected in low concentrations, it
      could also be used as a tracer gas to measure functional residual capacity and
      ventilation homogeneity. The aim of the present study was to validate functional
      residual capacity measurements by heptafluoropropane wash-in/wash-out (0.8%)
      during mechanical ventilation in small, surfactant-depleted lungs using a newborn
      piglet model. DESIGN: Prospective laboratory and animal trial. SETTING: Animal
      laboratory in a university setting. SUBJECTS: Sixteen newborn piglets (age<12
      hrs, median weight 1390 g [705-4200 g]) before and after surfactant depletion
      (Pao2<100 torr in Fio2=1.0) by lung lavage. INTERVENTIONS: Heptafluoropropane was
      measured with a new infrared mainstream sensor connected with the flow sensor of
      the Drager Babylog 8000. Accuracy and precision of the measurement technique were
      tested in a mechanical lung model with a volume range from 11 to 35 mL.
      Reproducibility of the method and its sensitivity to detect changes of functional
      residual capacity were assessed in vivo by variation of ventilatory variables.
      MEASUREMENTS AND MAIN RESULTS: In vitro the absolute error of functional residual
      capacity was <1 mL (relative errors<3%) with a coefficient of variation<4%. The
      coefficient of variation of consecutive in vivo measurements was only slightly
      higher (<5.1%). Measurement of heptafluoropropane concentrations in blood showed
      no significant accumulation for repeated functional residual capacity
      measurements within short time periods. After lung lavage, the functional
      residual capacity decreased from 20.9 mL/kg to 14.5 mL/kg (p<.05) despite
      increased ventilatory pressures, and lung clearance index (p<.001) and moment
      ratios (p<.01) increased significantly due to uneven alveolar ventilation. In
      healthy lungs, the increase in peak inflation pressure and positive end
      expiratory pressure by 3-4 cm H2O had only a moderate effect on functional
      residual capacity (20.9+/-8.6 vs. 26.0+/-11.9 mL/kg, p=.17) and no effect on
      ventilatory homogeneity, whereas in surfactant-depleted lungs the functional
      residual capacity increased from 14.5+/-6.7 mL/kg to 29.9+/-12.6 mL/kg (p<.001)
      and lung clearance index and moment ratios decreased significantly (p < .01).
      CONCLUSIONS: Heptafluoropropane is a suitable tracer gas for precise functional
      residual capacity measurements tested in vitro and allows for reproducible
      measurements in ventilated small lungs without any adverse effects on mechanical
      ventilation. The sensitivity of the method is sufficiently high to demonstrate
      the effect of changes in ventilatory settings on the functional residual capacity
      and ventilation homogeneity.

PMID- 16625131
TI  - Clinician statements and family satisfaction with family conferences in the
      intensive care unit.
AB  - OBJECTIVES: The quality of family-clinician communication in the intensive care
      unit is often inadequate, but little is known about specific clinician
      communication behaviors that might improve family satisfaction. In this
      exploratory analysis, we hypothesized that clinicians' communication behaviors
      providing emotional support to families during intensive care unit conferences
      would be associated with increased family satisfaction. DESIGN: We audiotaped 51
      intensive care unit family conferences in which withholding or withdrawing life
      support was discussed or bad news was delivered. Emotional support techniques
      used by clinicians during each conference were identified and coded using
      grounded theory. SETTING: Four Seattle hospitals. SUBJECTS: Family members of
      critically ill patients. INTERVENTIONS: Questionnaires rating satisfaction with
      communication were completed by 169 family members. MEASUREMENTS AND MAIN
      RESULTS: Linear regression with generalized estimating equation methods was used
      to analyze the association between the frequency of clinicians' emotionally
      supportive statements and family satisfaction. Increasing frequency of three
      types of clinicians' statements during family conferences was associated with
      increased family satisfaction: a) assurances that the patient will not be
      abandoned before death (p=.015); b) assurances that the patient will be
      comfortable and will not suffer (p=.029); and c) support for family's decisions
      about end- of-life care, including support for family's decision to withdraw or
      not to withdraw life-support (p=.005). CONCLUSIONS: Most family members
      participating in this study were quite satisfied with the communication in the
      family conferences. Specific clinician communication behaviors are associated
      with increased family satisfaction during family conferences among family members
      who are willing to have a family conference recorded. Our results suggest that
      clinicians in the intensive care unit may improve the experiences of families of
      critically ill patients by providing explicit support for decisions made by a
      family with regard to end-of-life care and by assuring families continuity of
      high-quality care with particular attention to the patient's comfort.

PMID- 16625132
TI  - Impact of patient monitoring on the diurnal pattern of medical emergency team
      activation.
AB  - OBJECTIVE: To study the impact of time of day, day of week and level of patient
      monitoring on medical emergency team (MET) activation. DESIGN: Retrospective
      observational study of all MET and cardiac arrest events between October 2001 and
      March 2005. SETTING: University of Pittsburgh Medical Center Presbyterian
      Hospital, a tertiary care teaching facility in the United States. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Cardiac arrest and MET event rate during the
      day (7 am to 6:59 pm) and night (7 pm to 6:59 am) overall; for weekdays and
      weekends; and from unmonitored, monitored, and intensive care units (ICUs). There
      were 605 cardiac arrest and 4,072 MET events. MET event rate was higher during
      the day than at night in unmonitored units (62% day vs. 38% night; p<.001) and
      monitored units (59% day vs. 41% night; p<.001) but not in ICUs (47% day vs. 53%
      night; p=.20). Unmonitored units had a greater daytime increase in MET event rate
      than monitored units (63% vs. 46%), whereas ICUs showed an 11% decline compared
      with night. The MET day vs. night difference was greater on weekdays (65% day vs.
      35% night; p<.001) than on weekends (56% day vs. 44% night; p<.001). Cardiac
      arrest event rate showed no diurnal pattern in any unit setting but had a higher
      daytime event rate during weekdays (57% day vs. 43% night; p=.004). CONCLUSIONS:
      More MET events take place during the day. MET events in unmonitored units have a
      greater diurnal variability than those from monitored units. ICUs show no diurnal
      variation in MET event rate. Our results suggest a significant variability in the
      hospital ability to consistently detect patients who meet MET activation
      criteria.

PMID- 16625133
TI  - Rapid induction of cerebral hypothermia by aortic flush during normovolemic
      cardiac arrest in pigs.
AB  - OBJECTIVE: Induction of deep cerebral hypothermia before reperfusion might
      improve neurologic outcome after cardiac arrest. We hypothesized that an aortic
      flush with cold saline during cardiac arrest is able to induce deep cerebral
      hypothermia and that the cooling efficiency can be enhanced by a) increasing the
      arteriovenous pressure gradient during the flush with vasopressin; b) improving
      the cerebral microcirculation during the flush with the thrombolytic agent
      alteplase; and c) increasing the arteriovenous pressure gradient further with
      venting the right heart by draining blood during the flush. DESIGN: Prospective
      randomized experimental study. SETTING: University research laboratory. SUBJECTS:
      Twenty-four pigs Large White breed (31-42 kg). INTERVENTIONS: After 10 mins of
      ventricular fibrillation, pigs received an aortic flush (100 mL/kg, 4 degrees C,
      flow rate 35 mL/kg/min) into the descending aorta via a balloon catheter. The
      animals were subjected randomly to either an aortic flush with saline, saline
      plus vasopressin 1.2 IU/kg, saline plus alteplase 1 mg/kg, saline plus a
      combination of vasopressin 1.2 IU/kg and alteplase 1 mg/kg, or saline plus
      vasopressin 1.2 IU/kg and venting the right heart. Arterial and venous pressures
      and brain temperatures were recorded for an observation time of 10 mins after
      flush. MEASUREMENTS AND MAIN RESULTS: A sufficient arteriovenous pressure
      gradient and deep cerebral hypothermia were only achieved with a flush containing
      vasopressin (brain temperature 16.1+/-1.3 degrees C in the vasopressin group vs.
      35.4+/-1.5 degrees C in the saline group, p<.001); combining vasopressin with
      alteplase, or venting the right heart, did not further enhance the cooling
      efficiency of the flush. CONCLUSIONS: A cold saline aortic flush with vasopressin
      rapidly decreases brain temperature during prolonged normovolemic cardiac arrest
      in pigs. Whether deep cerebral hypothermia induced before reperfusion can improve
      neurologic outcome after cardiac arrest needs further investigation in large
      animal outcome studies.

PMID- 16625134
TI  - Sepsis-induced lung injury in rats increases alveolar epithelial vulnerability to
      stretch.
AB  - OBJECTIVE: Previous in vitro models have shown that cellular deformation causes
      dose-dependent injury and death in healthy rat alveolar epithelial cells (AECs).
      We compared the viability of AECs from septic rats with those from nonseptic rats
      after 1 hr of cyclic equibiaxial stretch. We hypothesized that sepsis would
      increase stretch-induced cell death. DESIGN: Laboratory investigation. SETTING:
      University research laboratory. SUBJECTS: Thirty-seven male Sprague-Dawley rats
      weighing 240-260 g. INTERVENTIONS: Anesthetized rats were subjected to cecal
      ligation and double puncture (2CLP) or sham laparotomy without cecal ligation or
      puncture (sham). After 24 or 48 hrs, AECs were isolated, seeded in custom wells,
      and maintained in culture for 48 hrs before study. AECs were stretched cyclically
      (15/min) to a 0%, 12%, 25%, or 37% change in surface area (DeltaSA) for 1 hr.
      Cell viability, phenotypic markers, and nuclear factor-kappaB intracellular
      localization were assessed using fluorescent immunocytochemistry. MEASUREMENTS
      AND MAIN RESULTS: Phase and fluorescent images were evaluated for all studies.
      Response to stretch was the same at 24 and 48 hrs after 2CLP. Relative to sham,
      2CLP significantly increased cell death at 25 and 37% DeltaSA (p<.003, analysis
      of variance). Relative to sham, 2CLP did not alter expression of type I or type
      II phenotypic markers. Nuclear factor-kappaB within the nuclear compartment was
      observed after 2CLP in unstretched cells and after 1 hr of cyclic stretch at 37%
      DeltaSA. In sham, nuclear factor-kappaB within the nuclear compartment was seen
      only after stretch. CONCLUSIONS: AECs isolated from septic rats are more
      vulnerable to mechanical deformation injury than AECs from nonseptic animals.

PMID- 16625135
TI  - Continuous assessment of cerebrovascular autoregulation after traumatic brain
      injury using brain tissue oxygen pressure reactivity.
AB  - OBJECTIVE: To evaluate whether two newly developed indexes of brain tissue oxygen
      pressure reactivity (ORx and bPtio2) provide information on the status of
      cerebrovascular autoregulation after traumatic brain injury. This was
      accomplished by analyzing the relationship between these indexes and an index of
      cerebrovascular pressure reactivity (PRx). PRx is an established parameter for
      estimation of cerebrovascular autoregulation. DESIGN: Retrospective analysis of
      prospectively collected data. SETTING: Neurosurgical intensive care unit of a
      university hospital. PATIENTS: Twenty-seven patients suffering from severe
      traumatic brain injury. INTERVENTIONS: Continuous monitoring of mean arterial
      blood pressure, intracranial pressure, cerebral perfusion pressure, and partial
      pressure of brain tissue oxygen (Ptio2) was performed for an average of 6.5 days.
      ORx was calculated as a moving correlation coefficient between values of cerebral
      perfusion pressure and Ptio2. The bPtio2 was calculated as a moving value of the
      slope of the linear regression function between cerebral perfusion pressure and
      Ptio2. PRx was calculated as a moving correlation coefficient between values for
      intracranial pressure and mean arterial blood pressure. Outcome was assessed at 6
      months after traumatic brain injury (Glasgow Outcome Scale). MEASUREMENTS AND
      MAIN RESULTS: Both ORx and bPtio2 correlated significantly with PRx (r=.55 for
      ORx, r=.52 for bPtio2, p<.01). PRx and ORx showed a significantly negative
      correlation to the monitored Ptio2 values (r=-.42 for PRx, r=-.41 for ORx, p<.05)
      and outcome (r=-.52 for PRx, r=-.62 for ORx, p<.01), whereas bPtio2 did not.
      CONCLUSIONS: ORx and, to a lesser extent, bPtio2 correlated with the
      autoregulatory marker PRx and provide additional information about the status of
      cerebrovascular autoregulation after traumatic brain injury. The data also
      suggested that patients with impaired autoregulation are at increased risk for
      secondary cerebral hypoxia.

PMID- 16625138
TI  - Advice for travelers.

PMID- 16625136
TI  - Impact of systematic evaluation of pain and agitation in an intensive care unit.
AB  - OBJECTIVE: To measure the impact of implementation of the systematic evaluation
      of pain and agitation by nurses using the Behavioral Pain Scale (BPS), the
      Numerical Rating Scale (NRS) for pain, and the Richmond Agitation Sedation Scale
      (RASS) associated with medical staff education in analgesia and sedation
      management in intensive care unit (ICU) patients. DESIGN: Two-phase, prospective,
      controlled study. SETTING: Twelve-bed medical-surgical ICU in a university
      hospital. PATIENTS: Consecutive patients staying >24 hrs in ICU. INTERVENTIONS:
      BPS, NRS, and RASS were measured twice daily, at rest, by independent observers
      during 21 wks (control group) and after 4 wks of training, by nurses during 29
      wks (intervention group). In the intervention group, the treating physician was
      alerted in case of pain defined by BPS>5 or NRS>3 or in case of agitation defined
      by RASS>1. MEASUREMENTS AND MAIN RESULTS: A total of 230 patients were included
      (control group, n=100; intervention group, n=130). Baseline characteristics were
      not significantly different. The incidence of pain and agitation decreased
      significantly in the intervention group: 63% vs. 42% (p=.002) and 29% vs. 12%
      (p=.002), respectively. Rate of severe pain and agitation events defined by NRS>6
      and RASS>2, respectively, also decreased significantly. There were significantly
      more therapeutic changes in the intervention group in the way of an escalation
      but also in the way of a de-escalation for analgesic and psychoactive drugs.
      Compared with the control group, there was a marked decrease in the duration of
      mechanical ventilation (120 [interquartile range 48-312] vs. 65 (24-192) hrs,
      p=.01) and nosocomial infections rate (17% vs. 8%, p<.05) in the intervention
      group. There was no significant difference in median length of stay (9 [4, 15]
      vs. 7 [4, 13] days) and mortality in ICU (12 vs. 15%). CONCLUSIONS: Systematic
      evaluation of pain and agitation, and analgesics and sedatives need was
      associated with a decrease in incidence of pain and agitation, duration of
      mechanical ventilation and nosocomial infections.

PMID- 16625139
TI  - Clopidogrel (Plavix) revisited.

PMID- 16625140
TI  - Lenalidomide (Revlimid) for anemia of myelodysplastic syndrome.

PMID- 16625142
TI  - Insuline glusine (Apidra): a new rapid-acting insulin.
AB  - The third one so far. Does it offer any advantage over the other two?

PMID- 16625143
TI  - Rituximab (Rituxan) for rheumatoid arthritis.

PMID- 16625144
TI  - Deferasirox (Exjade): a new iron chelator.

PMID- 16625145
TI  - Refractory anemia in a patient with allergy to intravenous iron drugs.

PMID- 16625146
TI  - Humoral hypercalcemia of malignancy presenting after oncologic surgery.

PMID- 16625147
TI  - An improved method for primary culture of rat podocytes.
AB  - A gentle method to isolate glomeruli simply by cutting renal cortices without
      forced sieving was devised in our previous study of primary podocyte culture.
      Yields of glomeruli isolated by this method, however, were too small to perform
      subculture or biological assays. In the present study, we tried an isolation
      method with magnetic beads and collagenase to increase the yields. Rat kidneys
      were perfused with magnetic particles. Renal cortices were digested with
      collagenase and filtered. Utilizing magnetic particles trapped within glomeruli,
      glomeruli were collected by attractive power of a magnet and cultured. The number
      of glomeruli isolated from one adult rat was more than 20,000 and the purity was
      more than 97%. About half of them were attached to culture dishes and exhibited
      cellular outgrowths, which were identified as podocytes by their distinct
      staining for podocyte markers. After 3 days of primary culture, the cellular
      outgrowths were subcultured. Approximately 60 podocytes were obtained per
      attached glomerulus. Their significant expression of podocytes markers was
      demonstrated by immunostaining and quantitative reverse transcriptase-polymerase
      chain reaction. The isolation method with magnetic beads and collagenase provides
      a number of glomeruli suitable for primary podocyte culture.

PMID- 16625149
TI  - HIV-related nephropathy: a South African perspective.
AB  - Human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) is an important
      cause of renal failure in those of African origin. A number of other kidney
      diseases occur in HIV-positive patients. We conducted a retrospective review of
      renal biopsies in HIV-positive Black African patients to determine the prevalence
      of both 'classic HIVAN' and non-HIVAN pathologies in this group. Clinical and
      laboratory data from HIV-positive patients who underwent renal biopsy from 1st
      January 2003 to 31st December 2004 were collected. Similar information on HIV
      negative patients biopsied during the same period was also recorded by way of
      comparison to try and assess the influence of the virus on renal histologic
      patterns. HIV-positive group - 99 biopsies were suitable for study. The main
      histologic categories were 'classic HIVAN' (27%) and HIV immune complex kidney
      disease ('HIVICK') (21%). The subepithelial immune deposits in 'HIVICK' induced a
      newly described 'ball-in-cup' basement membrane reaction. Other
      glomerulonephritides included membranous, post-infectious disease, mesangial
      hyperplasia, and immunoglobulin A nephropathy. Overlapping clinical presentations
      prevented pre-biopsy histologic predictions. HIV-negative group - There were no
      examples of collapsing focal segmental glomerulosclerosis or nonspecific immune
      complex disease, but increased numbers of minimal change and
      membranoproliferative disease. 'Classic HIVAN' accounted for less than a third of
      the nephropathies occurring in HIV-positive Black South Africans. 'HIVICK' is
      another important cause of chronic kidney disease in this group. Future research
      is needed into the earlier detection and treatment of these diseases, which have
      a high mortality in our context.

PMID- 16625148
TI  - Upregulation of chemokine CXCL1/KC by leptospiral membrane lipoprotein
      preparation in renal tubule epithelial cells.
AB  - We have previously shown that leptospiral membrane lipoprotein preparation (LMLP)
      extracted from pathogenic Leptospira santarosai serovar Shermani stimulates the
      secretion of pro-inflammatory mediators in renal tubule epithelial cells, and
      implicated its role in the initiation of tubulointerstitial nephritis. Renal
      tubulointerstitial injury is characterized by inflammatory cell infiltrate;
      however, the stimuli for leukocyte recruitment are not fully understood. Initial
      studies by cytokine protein array analysis revealed significant upregulation of
      neutrophil-chemoattractant keratinocyte-derived chemokine (CXCL1/KC) at nanogram
      range of LMLP stimulation in cultured murine proximal tubule cells (PTCs). As
      PTCs express Toll-like receptors (TLRs), this study investigated the roles of TLR
      signaling pathways in PTCs stimulated by LMLP and its relation to CXCL1/KC
      secretion. The LMLP stimulated the early secretion of CXCL1/KC and enhanced the
      level of TLR2 mRNA expression in PTCs through time- and dose-dependent effect.
      The LMLP-stimulated secretion of human growth-related oncogene alpha, a
      functional homolog to murine KC, in TLR-defective human embryonic kidney 293
      cells transiently transfected with TLR2-expressing plasmids and the response was
      augmented by coexpression of TLR1 and TLR2. Moreover, silencing of TLR2, myeloid
      differentiation factor 88, and TNF receptor-associated factor 6 with specific
      small interfering RNA significantly reduces the response caused by LMLP in PTCs.
      The LMLP-stimulated CXCL1/KC secretion was also significantly reduced by pre
      incubating PTCs with a specific p38 inhibitor. These results indicate that LMLP
      stimulates the production of CXCL1/KC to recruit polymorphonuclear neutrophils at
      the site of inflammation through a TLR2-mediated pathway in renal tubule cells.

PMID- 16625150
TI  - Protective role of selectin ligand inhibition in a large animal model of kidney
      ischemia-reperfusion injury.
AB  - Experiments in rodents have demonstrated an important role for selectins in
      kidney ischemia-reperfusion injury (IRI). However, the relevance of this in
      larger mammals, as well as the impact on long-term structure and function is
      unknown. We tested the hypothesis that small molecule selectin ligand inhibition
      attenuates IRI, cellular inflammation, and long-term effects on renal
      interstitial fibrosis. We used a porcine model of kidney IRI and used Texas
      Biotechnology Corporation (TBC)-1269, a selectin ligand inhibitor. Renal
      function, tissue inflammation, and tubulointerstitial fibrosis development were
      evaluated up to 16 weeks. Both warm and cold ischemia models were studied for
      relevance to native and transplant kidney injury. Pigs treated with TBC-1269
      during 45 min of warm ischemia (WI) showed significantly increased glomerular
      filtration rate compared to control animals. In pigs with severe IRI (WI for 60
      min), TBC-1269 treatment during IRI significantly increased renal recovery.
      Cellular inflammation was strongly reduced, particularly influx of CD4 cells.
      Quantitative measurement of fibrosis by picrosirius red staining showed strong
      reduction in TBC-1269-treated groups. TBC-1269 also reduced cold IRI,
      inflammation, and fibrosis in kidneys preserved for 24 h at 4 degrees C and
      autotransplanted. The selectin ligand inhibitor TBC-1269 provides a novel and
      effective approach to attenuate IRI in both warm and cold ischemia in large
      mammals, in both short and long terms. Selectin ligand inhibition is an
      attractive strategy for evaluation in human kidney IRI.

PMID- 16625151
TI  - Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis
      induced by obstructive injury.
AB  - Transforming growth factor-beta (TGF-beta) plays a critical role in the
      progression of renal fibrosis. The activity of TGF-beta is tightly controlled by
      various mechanisms, among which antagonizing Smad-mediated gene transcription by
      co-repressors represents one of the important components. We investigated the
      expression, degradation, and ubiquitination of Smad transcriptional co-repressors
      SnoN (ski-related novel gene N) and Ski (Sloan-Kettering Institute proto
      oncogene) in renal fibrogenesis. We also studied the involvement of Smad
      ubiquitination regulatory factor 2 (Smurf2) in ubiquitination of SnoN protein.
      The kidneys of mice with unilateral ureteral obstruction (UUO) and those of sham
      operated mice were used. Renal lesions and the expression of TGF-beta1, type I
      collagen, SnoN, Ski, and Smurf2 were examined by immunohistochemistry, Western
      blot, and/or real-time reverse transcriptase-polymerase chain reaction.
      Degradation and ubiquitination of SnoN/Ski proteins were also investigated. The
      obstructed kidneys of UUO mice showed progressive tubulointerstitial fibrosis,
      high expression levels of TGF-beta1, type I collagen, SnoN and Ski mRNAs, and low
      levels of SnoN and Ski proteins. Both degradation and ubiquitination of SnoN/Ski
      proteins were markedly increased in the obstructed kidneys, in which Smurf2
      expression was increased. Smurf2 immunodepletion in extracts of obstructed
      kidneys resulted in reduced ubiquitination of SnoN. Our results suggest that the
      reduction of SnoN/Ski proteins resulting from increased ubiquitin-dependent
      degradation is involved in the progression of tubulointerstitial fibrosis.

PMID- 16625152
TI  - Visualization of molecular interactions by fluorescence complementation.
AB  - The visualization of protein complexes in living cells enables the examination of
      protein interactions in their normal environment and the determination of their
      subcellular localization. The bimolecular fluorescence complementation assay has
      been used to visualize interactions among multiple proteins in many cell types
      and organisms. Modified forms of this assay have been used to visualize the
      competition between alternative interaction partners and the covalent
      modification of proteins by ubiquitin-family peptides.

PMID- 16625157
TI  - Learning from Chernobyl.

PMID- 16625159
TI  - Drugs tests on trial.

PMID- 16625153
TI  - Lipid rafts: contentious only from simplistic standpoints.
AB  - The hypothesis that lipid rafts exist in plasma membranes and have crucial
      biological functions remains controversial. The lateral heterogeneity of proteins
      in the plasma membrane is undisputed, but the contribution of cholesterol
      dependent lipid assemblies to this complex, non-random organization promotes
      vigorous debate. In the light of recent studies with model membranes,
      computational modelling and innovative cell biology, I propose an updated model
      of lipid rafts that readily accommodates diverse views on plasma-membrane micro
      organization.

PMID- 16625161
TI  - Glint from tenth planet dazzles astronomers.

PMID- 16625162
TI  - Societies spurn women editors.

PMID- 16625164
TI  - Lakes linked beneath Antarctic ice.

PMID- 16625165
TI  - Wanted: cancer boss.

PMID- 16625167
TI  - Special report: counting the dead.

PMID- 16625168
TI  - Nuclear power: Chernobyl and the future: when the price is right.

PMID- 16625169
TI  - Nuclear waste: Chernobyl and the future: forward planning.

PMID- 16625170
TI  - Handle with care.

PMID- 16625173
TI  - Reviewers peering from under a pile of 'omics' data.

PMID- 16625174
TI  - Eastern European science needs sweeping changes.

PMID- 16625175
TI  - Ethics: China already has clear stem-cell guidelines.

PMID- 16625176
TI  - Ethics of using employees' eggs in cloning research.

PMID- 16625177
TI  - Chernobyl and the future: too soon for a final diagnosis.

PMID- 16625182
TI  - Neuroscience: spikes too kinky in the cortex?

PMID- 16625183
TI  - Glaciology: ice-sheet plumbing in Antarctica.

PMID- 16625184
TI  - Evolution: spot on (and off).

PMID- 16625185
TI  - Astronomy: trouble at first light.

PMID- 16625186
TI  - Biomechanics: a pneumo-hydrostatic skeleton in land crabs.
AB  - Like their aquatic counterparts, terrestrial crabs repeatedly shed their rigid
      exoskeleton during moulting. But in the case of land crabs, little water is
      available to provide a temporary hydrostatic skeleton before the new skeleton
      hardens, and air does not provide the buoyancy necessary to support the animal.
      Here we show that whenever its exoskeleton is shed, the blackback land crab
      Gecarcinus lateralis relies on an unconventional type of hydrostatic skeleton
      that uses both gas and liquid (a 'pneumo-hydrostat'). To our knowledge, this is
      the first experimental evidence for a locomotor skeleton that depends on a gas.
      It establishes a new category of hydrostatic skeletal support and possibly a
      critical adaptation to life on land for the Crustacea.

PMID- 16625187
TI  - Weak pairwise correlations imply strongly correlated network states in a neural
      population.
AB  - Biological networks have so many possible states that exhaustive sampling is
      impossible. Successful analysis thus depends on simplifying hypotheses, but
      experiments on many systems hint that complicated, higher-order interactions
      among large groups of elements have an important role. Here we show, in the
      vertebrate retina, that weak correlations between pairs of neurons coexist with
      strongly collective behaviour in the responses of ten or more neurons. We find
      that this collective behaviour is described quantitatively by models that capture
      the observed pairwise correlations but assume no higher-order interactions. These
      maximum entropy models are equivalent to Ising models, and predict that larger
      networks are completely dominated by correlation effects. This suggests that the
      neural code has associative or error-correcting properties, and we provide
      preliminary evidence for such behaviour. As a first test for the generality of
      these ideas, we show that similar results are obtained from networks of cultured
      cortical neurons.

PMID- 16625188
TI  - Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex.
AB  - Hsp90 (heat shock protein of 90 kDa) is a ubiquitous molecular chaperone
      responsible for the assembly and regulation of many eukaryotic signalling systems
      and is an emerging target for rational chemotherapy of many cancers. Although the
      structures of isolated domains of Hsp90 have been determined, the arrangement and
      ATP-dependent dynamics of these in the full Hsp90 dimer have been elusive and
      contentious. Here we present the crystal structure of full-length yeast Hsp90 in
      complex with an ATP analogue and the co-chaperone p23/Sba1. The structure reveals
      the complex architecture of the 'closed' state of the Hsp90 chaperone, the
      extensive interactions between domains and between protein chains, the detailed
      conformational changes in the amino-terminal domain that accompany ATP binding,
      and the structural basis for stabilization of the closed state by p23/Sba1.
      Contrary to expectations, the closed Hsp90 would not enclose its client proteins
      but provides a bipartite binding surface whose formation and disruption are
      coupled to the chaperone ATPase cycle.

PMID- 16625190
TI  - Experimental determination of entanglement with a single measurement.
AB  - Nearly all protocols requiring shared quantum information--such as quantum
      teleportation or key distribution--rely on entanglement between distant parties.
      However, entanglement is difficult to characterize experimentally. All existing
      techniques for doing so, including entanglement witnesses or Bell inequalities,
      disclose the entanglement of some quantum states but fail for other states;
      therefore, they cannot provide satisfactory results in general. Such methods are
      fundamentally different from entanglement measures that, by definition, quantify
      the amount of entanglement in any state. However, these measures suffer from the
      severe disadvantage that they typically are not directly accessible in laboratory
      experiments. Here we report a linear optics experiment in which we directly
      observe a pure-state entanglement measure, namely concurrence. Our measurement
      set-up includes two copies of a quantum state: these 'twin' states are prepared
      in the polarization and momentum degrees of freedom of two photons, and
      concurrence is measured with a single, local measurement on just one of the
      photons.

PMID- 16625191
TI  - Polarons and confinement of electronic motion to two dimensions in a layered
      manganite.
AB  - A remarkable feature of layered transition--metal oxides-most famously, the high
      temperature superconductors--is that they can display hugely anisotropic
      electrical and optical properties (for example, seeming to be insulating
      perpendicular to the layers and metallic within them), even when prepared as bulk
      three-dimensional single crystals. This is the phenomenon of 'confinement', a
      concept at odds with the conventional theory of solids, and recognized as due to
      magnetic and electron-lattice interactions within the layers that must be
      overcome at a substantial energy cost if electrons are to be transferred between
      layers. The associated energy gap, or 'pseudogap', is particularly obvious in
      experiments where charge is moved perpendicular to the planes, most notably
      scanning tunnelling microscopy and polarized infrared spectroscopy. Here, using
      the same experimental tools, we show that there is a second family of transition
      metal oxides--the layered manganites La(2-2x)Sr(1+2x)Mn2O7--with even more
      extreme confinement and pseudogap effects. The data demonstrate quantitatively
      that because the charge carriers are attached to polarons (lattice- and spin
      textures within the planes), it is as difficult to remove them from the planes
      through vacuum-tunnelling into a conventional metallic tip, as it is for them to
      move between Mn-rich layers within the material itself.

PMID- 16625189
TI  - A low level of extragalactic background light as revealed by gamma-rays from
      blazars.
AB  - The diffuse extragalactic background light consists of the sum of the starlight
      emitted by galaxies through the history of the Universe, and it could also have
      an important contribution from the 'first stars', which may have formed before
      galaxy formation began. Direct measurements are difficult and not yet conclusive,
      owing to the large uncertainties caused by the bright foreground emission
      associated with zodiacal light. An alternative approach is to study the
      absorption features imprinted on the gamma-ray spectra of distant extragalactic
      objects by interactions of those photons with the background light photons. Here
      we report the discovery of gamma-ray emission from the blazars H 2356 - 309 and
      1ES 1101 - 232, at redshifts z = 0.165 and z = 0.186, respectively. Their
      unexpectedly hard spectra provide an upper limit on the background light at
      optical/near-infrared wavelengths that appears to be very close to the lower
      limit given by the integrated light of resolved galaxies. The background flux at
      these wavelengths accordingly seems to be strongly dominated by the direct
      starlight from galaxies, thus excluding a large contribution from other sources
      in particular from the first stars formed. This result also indicates that
      intergalactic space is more transparent to gamma-rays than previously thought.

PMID- 16625192
TI  - Climate sensitivity constrained by temperature reconstructions over the past
      seven centuries.
AB  - The magnitude and impact of future global warming depends on the sensitivity of
      the climate system to changes in greenhouse gas concentrations. The commonly
      accepted range for the equilibrium global mean temperature change in response to
      a doubling of the atmospheric carbon dioxide concentration, termed climate
      sensitivity, is 1.5-4.5 K (ref. 2). A number of observational studies, however,
      find a substantial probability of significantly higher sensitivities, yielding
      upper limits on climate sensitivity of 7.7 K to above 9 K (refs 3-8). Here we
      demonstrate that such observational estimates of climate sensitivity can be
      tightened if reconstructions of Northern Hemisphere temperature over the past
      several centuries are considered. We use large-ensemble energy balance modelling
      and simulate the temperature response to past solar, volcanic and greenhouse gas
      forcing to determine which climate sensitivities yield simulations that are in
      agreement with proxy reconstructions. After accounting for the uncertainty in
      reconstructions and estimates of past external forcing, we find an independent
      estimate of climate sensitivity that is very similar to those from instrumental
      data. If the latter are combined with the result from all proxy reconstructions,
      then the 5-95 per cent range shrinks to 1.5-6.2 K, thus substantially reducing
      the probability of very high climate sensitivity.

PMID- 16625193
TI  - Rapid discharge connects Antarctic subglacial lakes.
AB  - The existence of many subglacial lakes provides clear evidence for the widespread
      presence of water beneath the East Antarctic ice sheet, but the hydrology beneath
      this ice mass is poorly understood. Such knowledge is critical to understanding
      ice flow, basal water transfer to the ice margin, glacial landform development
      and subglacial lake habitats. Here we present ice-sheet surface elevation changes
      in central East Antarctica that we interpret to represent rapid discharge from a
      subglacial lake. Our observations indicate that during a period of 16 months, 1.8
      km3 of water was transferred over 290 km to at least two other subglacial lakes.
      While viscous deformation of the ice roof above may moderate discharge, the
      intrinsic instability of such a system suggests that discharge events are a
      common mode of basal drainage. If large lakes, such as Lake Vostok or Lake
      Concordia, are pressurizing, it is possible that substantial discharges could
      reach the coast. Our observations conflict with expectations that subglacial
      lakes have long residence times and slow circulations, and we suggest that entire
      subglacial drainage basins may be flushed periodically. The rapid transfer of
      water between lakes would result in large-scale solute and microbe relocation,
      and drainage system contamination from in situ exploration is, therefore, a
      distinct risk.

PMID- 16625194
TI  - A Cretaceous terrestrial snake with robust hindlimbs and a sacrum.
AB  - It has commonly been thought that snakes underwent progressive loss of their
      limbs by gradual diminution of their use. However, recent developmental and
      palaeontological discoveries suggest a more complex scenario of limb reduction,
      still poorly documented in the fossil record. Here we report a fossil snake with
      a sacrum supporting a pelvic girdle and robust, functional legs outside the
      ribcage. The new fossil, from the Upper Cretaceous period of Patagonia, fills an
      important gap in the evolutionary progression towards limblessness because other
      known fossil snakes with developed hindlimbs, the marine Haasiophis, Pachyrhachis
      and Eupodophis, lack a sacral region. Phylogenetic analysis shows that the new
      fossil is the most primitive (basal) snake known and that all other limbed fossil
      snakes are closer to the more advanced macrostomatan snakes, a group including
      boas, pythons and colubroids. The new fossil retains several features associated
      with a subterranean or surface dwelling life that are also present in primitive
      extant snake lineages, supporting the hypothesis of a terrestrial rather than
      marine origin of snakes.

PMID- 16625195
TI  - Evolution of cooperative strategies from first principles.
AB  - One of the greatest challenges in the modern biological and social sciences is to
      understand the evolution of cooperative behaviour. General outlines of the answer
      to this puzzle are currently emerging as a result of developments in the theories
      of kin selection, reciprocity, multilevel selection and cultural group selection.
      The main conceptual tool used in probing the logical coherence of proposed
      explanations has been game theory, including both analytical models and agent
      based simulations. The game-theoretic approach yields clear-cut results but
      assumes, as a rule, a simple structure of payoffs and a small set of possible
      strategies. Here we propose a more stringent test of the theory by developing a
      computer model with a considerably extended spectrum of possible strategies. In
      our model, agents are endowed with a limited set of receptors, a set of
      elementary actions and a neural net in between. Behavioural strategies are not
      predetermined; instead, the process of evolution constructs and reconstructs them
      from elementary actions. Two new strategies of cooperative attack and defence
      emerge in simulations, as well as the well-known dove, hawk and bourgeois
      strategies. Our results indicate that cooperative strategies can evolve even
      under such minimalist assumptions, provided that agents are capable of perceiving
      heritable external markers of other agents.

PMID- 16625196
TI  - DNA sequence of human chromosome 17 and analysis of rearrangement in the human
      lineage.
AB  - Chromosome 17 is unusual among the human chromosomes in many respects. It is the
      largest human autosome with orthology to only a single mouse chromosome, mapping
      entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in
      protein-coding genes, having the second highest gene density in the genome. It is
      also enriched in segmental duplications, ranking third in density among the
      autosomes. Here we report a finished sequence for human chromosome 17, as well as
      a structural comparison with the finished sequence for mouse chromosome 11, the
      first finished mouse chromosome. Comparison of the orthologous regions reveals
      striking differences. In contrast to the typical pattern seen in mammalian
      evolution, the human sequence has undergone extensive intrachromosomal
      rearrangement, whereas the mouse sequence has been remarkably stable. Moreover,
      although the human sequence has a high density of segmental duplication, the
      mouse sequence has a very low density. Notably, these segmental duplications
      correspond closely to the sites of structural rearrangement, demonstrating a link
      between duplication and rearrangement. Examination of the main classes of
      duplicated segments provides insight into the dynamics underlying expansion of
      chromosome-specific, low-copy repeats in the human genome.

PMID- 16625197
TI  - Repeated morphological evolution through cis-regulatory changes in a pleiotropic
      gene.
AB  - The independent evolution of morphological similarities is widespread. For simple
      traits, such as overall body colour, repeated transitions by means of mutations
      in the same gene may be common. However, for more complex traits, the possible
      genetic paths may be more numerous; the molecular mechanisms underlying their
      independent origins and the extent to which they are constrained to follow
      certain genetic paths are largely unknown. Here we show that a male wing
      pigmentation pattern involved in courtship display has been gained and lost
      multiple times in a Drosophila clade. Each of the cases we have analysed (two
      gains and two losses) involved regulatory changes at the pleiotropic pigmentation
      gene yellow. Losses involved the parallel inactivation of the same cis-regulatory
      element (CRE), with changes at a few nucleotides sufficient to account for the
      functional divergence of one element between two sibling species. Surprisingly,
      two independent gains of wing spots resulted from the co-option of distinct
      ancestral CREs. These results demonstrate how the functional diversification of
      the modular CREs of pleiotropic genes contributes to evolutionary novelty and the
      independent evolution of morphological similarities.

PMID- 16625198
TI  - Unique features of action potential initiation in cortical neurons.
AB  - Neurons process and encode information by generating sequences of action
      potentials. For all spiking neurons, the encoding of single-neuron computations
      into sequences of spikes is biophysically determined by the cell's action
      potential-generating mechanism. It has recently been discovered that apparently
      minor modifications of this mechanism can qualitatively change the nature of
      neuronal encoding. Here we quantitatively analyse the dynamics of action
      potential initiation in cortical neurons in vivo, in vitro and in computational
      models. Unexpectedly, key features of the initiation dynamics of cortical neuron
      action potentials--their rapid initiation and variable onset potential--are
      outside the range of behaviours described by the classical Hodgkin-Huxley theory.
      We propose a new model based on the cooperative activation of sodium channels
      that reproduces the observed dynamics of action potential initiation. This new
      model predicts that Hodgkin-Huxley-type dynamics of action potential initiation
      can be induced by artificially decreasing the effective density of sodium
      channels. In vitro experiments confirm this prediction, supporting the hypothesis
      that cooperative sodium channel activation underlies the dynamics of action
      potential initiation in cortical neurons.

PMID- 16625199
TI  - Enhanced bacterial clearance and sepsis resistance in caspase-12-deficient mice.
AB  - Caspases function in both apoptosis and inflammatory cytokine processing and
      thereby have a role in resistance to sepsis. Here we describe a novel role for a
      caspase in dampening responses to bacterial infection. We show that in mice, gene
      targeted deletion of caspase-12 renders animals resistant to peritonitis and
      septic shock. The resulting survival advantage was conferred by the ability of
      the caspase-12-deficient mice to clear bacterial infection more efficiently than
      wild-type littermates. Caspase-12 dampened the production of the pro-inflammatory
      cytokines interleukin (IL)-1beta, IL-18 (interferon (IFN)-gamma inducing factor)
      and IFN-gamma, but not tumour-necrosis factor-alpha and IL-6, in response to
      various bacterial components that stimulate Toll-like receptor and NOD pathways.
      The IFN-gamma pathway was crucial in mediating survival of septic caspase-12
      deficient mice, because administration of neutralizing antibodies to IFN-gamma
      receptors ablated the survival advantage that otherwise occurred in these
      animals. Mechanistically, caspase-12 associated with caspase-1 and inhibited its
      activity. Notably, the protease function of caspase-12 was not necessary for this
      effect, as the catalytically inactive caspase-12 mutant Cys299Ala also inhibited
      caspase-1 and IL-1beta production to the same extent as wild-type caspase-12. In
      this regard, caspase-12 seems to be the cFLIP counterpart for regulating the
      inflammatory branch of the caspase cascade. In mice, caspase-12 deficiency
      confers resistance to sepsis and its presence exerts a dominant-negative
      suppressive effect on caspase-1, resulting in enhanced vulnerability to bacterial
      infection and septic mortality.

PMID- 16625200
TI  - Pharmaco-metabonomic phenotyping and personalized drug treatment.
AB  - There is a clear case for drug treatments to be selected according to the
      characteristics of an individual patient, in order to improve efficacy and reduce
      the number and severity of adverse drug reactions. However, such personalization
      of drug treatments requires the ability to predict how different individuals will
      respond to a particular drug/dose combination. After initial optimism, there is
      increasing recognition of the limitations of the pharmacogenomic approach, which
      does not take account of important environmental influences on drug absorption,
      distribution, metabolism and excretion. For instance, a major factor underlying
      inter-individual variation in drug effects is variation in metabolic phenotype,
      which is influenced not only by genotype but also by environmental factors such
      as nutritional status, the gut microbiota, age, disease and the co- or pre
      administration of other drugs. Thus, although genetic variation is clearly
      important, it seems unlikely that personalized drug therapy will be enabled for a
      wide range of major diseases using genomic knowledge alone. Here we describe an
      alternative and conceptually new 'pharmaco-metabonomic' approach to personalizing
      drug treatment, which uses a combination of pre-dose metabolite profiling and
      chemometrics to model and predict the responses of individual subjects. We
      provide proof-of-principle for this new approach, which is sensitive to both
      genetic and environmental influences, with a study of paracetamol (acetaminophen)
      administered to rats. We show pre-dose prediction of an aspect of the urinary
      drug metabolite profile and an association between pre-dose urinary composition
      and the extent of liver damage sustained after paracetamol administration.

PMID- 16625202
TI  - Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses.
AB  - The innate immune system senses viral infection by recognizing a variety of viral
      components (including double-stranded (ds)RNA) and triggers antiviral responses.
      The cytoplasmic helicase proteins RIG-I (retinoic-acid-inducible protein I, also
      known as Ddx58) and MDA5 (melanoma-differentiation-associated gene 5, also known
      as Ifih1 or Helicard) have been implicated in viral dsRNA recognition. In vitro
      studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine
      polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue. Although a critical
      role for RIG-I in the recognition of several RNA viruses has been clarified, the
      functional role of MDA5 and the relationship between these dsRNA detectors in
      vivo are yet to be determined. Here we use mice deficient in MDA5 (MDA5-/-) to
      show that MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes
      poly(I:C), and RIG-I detects in vitro transcribed dsRNAs. RNA viruses are also
      differentially recognized by RIG-I and MDA5. We find that RIG-I is essential for
      the production of interferons in response to RNA viruses including
      paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is
      critical for picornavirus detection. Furthermore, RIG-I-/- and MDA5-/- mice are
      highly susceptible to infection with these respective RNA viruses compared to
      control mice. Together, our data show that RIG-I and MDA5 distinguish different
      RNA viruses and are critical for host antiviral responses.

PMID- 16625203
TI  - Polycomb complexes repress developmental regulators in murine embryonic stem
      cells.
AB  - The mechanisms by which embryonic stem (ES) cells self-renew while maintaining
      the ability to differentiate into virtually all adult cell types are not well
      understood. Polycomb group (PcG) proteins are transcriptional repressors that
      help to maintain cellular identity during metazoan development by epigenetic
      modification of chromatin structure. PcG proteins have essential roles in early
      embryonic development and have been implicated in ES cell pluripotency, but few
      of their target genes are known in mammals. Here we show that PcG proteins
      directly repress a large cohort of developmental regulators in murine ES cells,
      the expression of which would otherwise promote differentiation. Using genome
      wide location analysis in murine ES cells, we found that the Polycomb repressive
      complexes PRC1 and PRC2 co-occupied 512 genes, many of which encode transcription
      factors with important roles in development. All of the co-occupied genes
      contained modified nucleosomes (trimethylated Lys 27 on histone H3). Consistent
      with a causal role in gene silencing in ES cells, PcG target genes were de
      repressed in cells deficient for the PRC2 component Eed, and were preferentially
      activated on induction of differentiation. Our results indicate that dynamic
      repression of developmental pathways by Polycomb complexes may be required for
      maintaining ES cell pluripotency and plasticity during embryonic development.

PMID- 16625204
TI  - Suppression of basal autophagy in neural cells causes neurodegenerative disease
      in mice.
AB  - Autophagy is an intracellular bulk degradation process through which a portion of
      the cytoplasm is delivered to lysosomes to be degraded. Although the primary role
      of autophagy in many organisms is in adaptation to starvation, autophagy is also
      thought to be important for normal turnover of cytoplasmic contents, particularly
      in quiescent cells such as neurons. Autophagy may have a protective role against
      the development of a number of neurodegenerative diseases. Here we report that
      loss of autophagy causes neurodegeneration even in the absence of any disease
      associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5)
      specifically in neural cells develop progressive deficits in motor function that
      are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons.
      In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then
      form aggregates and inclusions. These results suggest that the continuous
      clearance of diffuse cytosolic proteins through basal autophagy is important for
      preventing the accumulation of abnormal proteins, which can disrupt neural
      function and ultimately lead to neurodegeneration.

PMID- 16625205
TI  - Loss of autophagy in the central nervous system causes neurodegeneration in mice.
AB  - Protein quality-control, especially the removal of proteins with aberrant
      structures, has an important role in maintaining the homeostasis of non-dividing
      neural cells. In addition to the ubiquitin-proteasome system, emerging evidence
      points to the importance of autophagy--the bulk protein degradation pathway
      involved in starvation-induced and constitutive protein turnover--in the protein
      quality-control process. However, little is known about the precise roles of
      autophagy in neurons. Here we report that loss of Atg7 (autophagy-related 7), a
      gene essential for autophagy, leads to neurodegeneration. We found that mice
      lacking Atg7 specifically in the central nervous system showed behavioural
      defects, including abnormal limb-clasping reflexes and a reduction in coordinated
      movement, and died within 28 weeks of birth. Atg7 deficiency caused massive
      neuronal loss in the cerebral and cerebellar cortices. Notably, polyubiquitinated
      proteins accumulated in autophagy-deficient neurons as inclusion bodies, which
      increased in size and number with ageing. There was, however, no obvious
      alteration in proteasome function. Our results indicate that autophagy is
      essential for the survival of neural cells, and that impairment of autophagy is
      implicated in the pathogenesis of neurodegenerative disorders involving ubiquitin
      containing inclusion bodies.

PMID- 16625206
TI  - Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector
      immunity.
AB  - A common viral immune evasion strategy involves mutating viral surface proteins
      in order to evade host neutralizing antibodies. Such immune evasion tactics have
      not previously been intentionally applied to the development of novel viral gene
      delivery vectors that overcome the critical problem of anti-vector immunity.
      Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based
      vaccines for human immunodeficiency virus type 1 and other pathogens have proved
      highly immunogenic in preclinical studies but will probably be limited by the
      high prevalence of pre-existing anti-Ad5 immunity in human populations,
      particularly in the developing world. Here we show that rAd5 vectors can be
      engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5
      vectors in which the seven short hypervariable regions (HVRs) on the surface of
      the Ad5 hexon protein were replaced with the corresponding HVRs from the rare
      adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high
      titres and were stable through serial passages in vitro. HVR-chimaeric rAd5
      vectors expressing simian immunodeficiency virus Gag proved comparably
      immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In the
      presence of high levels of pre-existing anti-Ad5 immunity, the immunogenicity of
      HVR-chimaeric rAd5 vectors was not detectably suppressed, whereas the
      immunogenicity of parental rAd5 vectors was abrogated. These data demonstrate
      that functionally relevant Ad5-specific neutralizing antibodies are focused on
      epitopes located within the hexon HVRs. Moreover, these studies show that
      recombinant viral vectors can be engineered to circumvent pre-existing anti
      vector immunity by removing key neutralizing epitopes on the surface of viral
      capsid proteins. Such chimaeric viral vectors may have important practical
      implications for vaccination and gene therapy.

PMID- 16625207
TI  - Modulation of intracortical synaptic potentials by presynaptic somatic membrane
      potential.
AB  - Traditionally, neuronal operations in the cerebral cortex have been viewed as
      occurring through the interaction of synaptic potentials in the dendrite and
      soma, followed by the initiation of an action potential, typically in the axon.
      Propagation of this action potential to the synaptic terminals is widely believed
      to be the only form of rapid communication of information between the soma and
      axonal synapses, and hence to postsynaptic neurons. Here we show that the voltage
      fluctuations associated with dendrosomatic synaptic activity propagate
      significant distances along the axon, and that modest changes in the somatic
      membrane potential of the presynaptic neuron modulate the amplitude and duration
      of axonal action potentials and, through a Ca2+-dependent mechanism, the average
      amplitude of the postsynaptic potential evoked by these spikes. These results
      indicate that synaptic activity in the dendrite and soma controls not only the
      pattern of action potentials generated, but also the amplitude of the synaptic
      potentials that these action potentials initiate in local cortical circuits,
      resulting in synaptic transmission that is a mixture of triggered and graded
      (analogue) signals.

PMID- 16625208
TI  - Three-dimensional structure of the myosin V inhibited state by cryoelectron
      tomography.
AB  - Unconventional myosin V (myoV) is an actin-based molecular motor that has a key
      function in organelle and mRNA transport, as well as in membrane trafficking.
      MyoV was the first member of the myosin superfamily shown to be processive,
      meaning that a single motor protein can 'walk' hand-over-hand along an actin
      filament for many steps before detaching. Full-length myoV has a low actin
      activated MgATPase activity at low [Ca2+], whereas expressed constructs lacking
      the cargo-binding domain have a high activity regardless of [Ca2+] (refs 5-7).
      Hydrodynamic data and electron micrographs indicate that the active state is
      extended, whereas the inactive state is compact. Here we show the first three
      dimensional structure of the myoV inactive state. Each myoV molecule consists of
      two heads that contain an amino-terminal motor domain followed by a lever arm
      that binds six calmodulins. The heads are followed by a coiled-coil dimerization
      domain (S2) and a carboxy-terminal globular cargo-binding domain. In the inactive
      structure, bending of myoV at the head-S2 junction places the cargo-binding
      domain near the motor domain's ATP-binding pocket, indicating that ATPase
      inhibition might occur through decreased rates of nucleotide exchange. The actin
      binding interfaces are unobstructed, and the lever arm is oriented in a position
      typical of strong actin-binding states. This structure indicates that motor
      recycling after cargo delivery might occur through transport on actively
      treadmilling actin filaments rather than by diffusion.

PMID- 16625209
TI  - A distal enhancer and an ultraconserved exon are derived from a novel retroposon.
AB  - Hundreds of highly conserved distal cis-regulatory elements have been
      characterized so far in vertebrate genomes. Many thousands more are predicted on
      the basis of comparative genomics. However, in stark contrast to the genes that
      they regulate, in invertebrates virtually none of these regions can be traced by
      using sequence similarity, leaving their evolutionary origins obscure. Here we
      show that a class of conserved, primarily non-coding regions in tetrapods
      originated from a previously unknown short interspersed repetitive element (SINE)
      retroposon family that was active in the Sarcopterygii (lobe-finned fishes and
      terrestrial vertebrates) in the Silurian period at least 410 million years ago
      (ref. 4), and seems to be recently active in the 'living fossil' Indonesian
      coelacanth, Latimeria menadoensis. Using a mouse enhancer assay we show that one
      copy, 0.5 million bases from the neuro-developmental gene ISL1, is an enhancer
      that recapitulates multiple aspects of Isl1 expression patterns. Several other
      copies represent new, possibly regulatory, alternatively spliced exons in the
      middle of pre-existing Sarcopterygian genes. One of these, a more than 200-base
      pair ultraconserved region, 100% identical in mammals, and 80% identical to the
      coelacanth SINE, contains a 31-amino-acid-residue alternatively spliced exon of
      the messenger RNA processing gene PCBP2 (ref. 6). These add to a growing list of
      examples in which relics of transposable elements have acquired a function that
      serves their host, a process termed 'exaptation', and provide an origin for at
      least some of the many highly conserved vertebrate-specific genomic sequences.

PMID- 16625212
TI  - Identification of cartilage progenitor cells in the adult ear perichondrium:
      utilization for cartilage reconstruction.
AB  - For cartilage reconstruction, it is still difficult to obtain a sufficient volume
      of cartilage and to maintain its functional phenotype for a long period.
      Utilizing tissue stem cells is one approach to overcome such difficulties. We
      show here the presence of cartilage progenitor cells in the ear perichondrium of
      adult rabbits by 5-bromo-2'-deoxyuridine labeling, clonogenicity, and
      differentiation analyses. Long-term label-retaining cells were demonstrated in
      the perichondrium. Cells from the perichondrium, that is, perichondrocytes were
      mechanically isolated using a raspatory and maintained in D-MEM/F-12 medium with
      10% FCS. They proliferated more vigorously than chondrocytes from the cartilage.
      Perichondrocytes could differentiate into adipocytes as well as osteocytes in
      differentiation induction medium. For cartilage reconstruction in vivo,
      perichondrocytes were seeded on collagen sponge scaffolds and implanted in nude
      mice. After 4 weeks, the composites with perichondrocytes generated the same
      weight of cartilaginous tissue as those with chondrocytes. They produced
      glycosaminoglycan and type II collagen as shown by RT-PCR and immunohistochemical
      examination. On the contrary, rabbit bone marrow mesenchymal stem cells used as
      control could regenerate significantly smaller cartilage than perichondrocytes in
      the implant study. Based on these findings, we propose that the perichondrium
      containing tissue progenitor cells is one of the potential candidates for use in
      reconstructing cartilage and new therapeutic modalities.

PMID- 16625210
TI  - Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and
      metabolic regulation.
AB  - The eight catalytic subunits of the mammalian phosphoinositide-3-OH kinase
      (PI(3)K) family form the backbone of an evolutionarily conserved signalling
      pathway; however, the roles of most PI(3)K isoforms in organismal physiology and
      disease are unknown. To delineate the role of p110alpha, a ubiquitously expressed
      PI(3)K involved in tyrosine kinase and Ras signalling, here we generated mice
      carrying a knockin mutation (D933A) that abrogates p110alpha kinase activity.
      Homozygosity for this kinase-dead p110alpha led to embryonic lethality. Mice
      heterozygous for this mutation were viable and fertile, but displayed severely
      blunted signalling via insulin-receptor substrate (IRS) proteins, key mediators
      of insulin, insulin-like growth factor-1 and leptin action. Defective
      responsiveness to these hormones led to reduced somatic growth,
      hyperinsulinaemia, glucose intolerance, hyperphagia and increased adiposity in
      mice heterozygous for the D933A mutation. This signalling function of p110alpha
      derives from its highly selective recruitment and activation to IRS signalling
      complexes compared to p110beta, the other broadly expressed PI(3)K isoform, which
      did not contribute to IRS-associated PI(3)K activity. p110alpha was the principal
      IRS-associated PI(3)K in cancer cell lines. These findings demonstrate a critical
      role for p110alpha in growth factor and metabolic signalling and also suggest an
      explanation for selective mutation or overexpression of p110alpha in a variety of
      cancers.

PMID- 16625213
TI  - ICAM1 amino-acid variant K469E is associated with paediatric bronchial asthma and
      elevated sICAM1 levels.
AB  - Intercellular adhesion molecule-1 (ICAM1) acts as ligand for beta2-integrin
      molecules and mediates leucocyte trafficking to the site of inflammation.
      Intercellular adhesion molecule-1-deficient mice show impaired lymphocyte
      recruitment to the lung, less airway hyper-responsiveness and less lung
      inflammation than healthy controls. Thus, the aim of the study was to test common
      ICAM1 polymorphisms for association with paediatric asthma. Furthermore, we were
      interested in whether soluble ICAM1 (sICAM1) serum levels were in correlation
      with genotypes. The following polymorphisms in ICAM1 were genotyped on 352
      children with asthma and 270 controls: rs5491 (resulting in the amino-acid
      exchange K56M), rs5493 (G241S), rs5498 (K469E), rs5030400 (R478W) and rs885743 in
      the 3'-untranslated region. In addition, sICAM1 serum levels were measured. Only
      K469E and rs885743 were present in our populations. K469E showed association with
      asthma (P = 0.0037 with Armitage's trend test). Haplotype analysis by FAMHAP
      using both polymorphisms revealed association with asthma by P < 0.000001. In
      addition, serum sICAM1 levels were correlated with K469E genotypes (P = 0.009 by
      Kruskal-Wallis test). We conclude from our data that K469KE is associated with
      paediatric asthma in the German population. Furthermore, the same polymorphism is
      correlated with serum levels of sICAM1. Functional analyses have to further
      clarify the pathophysiological mechanism conferred by the polymorphisms.

PMID- 16625214
TI  - Multifactor dimensionality reduction reveals gene-gene interactions associated
      with multiple sclerosis susceptibility in African Americans.
AB  - Multiple sclerosis (MS) is a common disease of the central nervous system
      characterized by inflammation, myelin loss, gliosis, varying degrees of axonal
      pathology, and progressive neurological dysfunction. Multiple sclerosis exhibits
      many of the characteristics that distinguish complex genetic disorders including
      polygenic inheritance and environmental exposure risks. Here, we used a highly
      efficient multilocus genotyping assay representing variation in 34 genes
      associated with inflammatory pathways to explore gene-gene interactions and
      disease susceptibility in a well-characterized African-American case-control MS
      data set. We applied the multifactor dimensionality reduction (MDR) test to
      detect epistasis, and identified single-IL4R(Q576R)- and three-IL4R(Q576R),
      IL5RA(-80), CD14(-260)- locus association models that predict MS risk with 75-76%
      accuracy (P<0.01). These results demonstrate the importance of exploring both
      main effects and gene-gene interactions in the study of complex diseases.

PMID- 16625215
TI  - Evidence vs experience in neonatal medicine. Proceedings of the 2nd Annual
      Conference. June 2005. San Diego, California, USA.

PMID- 16625216
TI  - Patent ductus arteriosus: pathophysiology and management.
AB  - Patent ductus arteriosus (PDA) in preterm newborns prior to 28 weeks of gestation
      has led to many challenges regarding the type and timing of treatment regimens. A
      PDA results in increased pulmonary blood flow and redistribution of flow to other
      organs. Several co-morbidities (i.e., necrotizing enterocolitis, intracranial
      hemorrhage, pulmonary edema/hemorrhage, bronchopulmonary dysplasia, and
      retinopathy) are associated with the presence of a PDA, but whether or not a PDA
      is responsible for their development is still unclear. The prostaglandin
      inhibitor, indomethacin, is effective in the treatment of PDA. Questions
      regarding the optimal timing of the intervention--early prophylaxis or treatment,
      once signs and symptoms become evident--have challenged physicians for decades.
      Both evidence and experience are explored in this article. Comparative physiology
      between the full-term and preterm newborn and the barriers preventing the
      necessary cascade of events leading to permanent constriction of the PDA are
      reviewed.

PMID- 16625217
TI  - Fluid and electrolyte management in the very low birth weight neonate.
AB  - Fluid and electrolyte management in the very low birth weight infant is critical
      to survival. The amount of fluid present in the plasma, interstitial fluid, and
      cellular fluid changes throughout the fetal and neonatal period, presenting a
      challenging situation. One of the many factors influencing fluid requirements is
      the insensible water loss by mechanisms such as evaporation. Low birth weight
      infants are especially susceptible to this due to their large body surface area
      and immature skin, often resulting in hypernatremia and the complications
      associated with it. However, some infants may experience hyperkalemia,
      hyperglycemia, and/or hyponatremia, resulting in various other complications.
      Careful monitoring is essential in deciding how to manage these infants. This
      article aims to discuss the management of fluid and electrolytes in very low
      birth weight infants and address ways to decrease the morbidity and mortality
      associated with the imbalances in fluid and electrolytes seen in this population.

PMID- 16625220
TI  - Palliative care in the fetus and newborn.
AB  - The changing environment in neonatology and perinatology has led to the
      examination of issues surrounding palliative care. Newborn palliative care should
      be considered in three general areas: (1) Neonates at the limits of viability. As
      advances in technology and outcomes become available, it is the responsibility of
      the health-care community and society to reach a consensus regarding the limits
      of viability. (2) Neonates with lethal congenital anomalies. When appropriate,
      and diagnosis and prognosis are certain, why should a family be deprived the
      opportunity to choose palliative care for the unborn child? (3) Neonates not
      responsive to aggressive medical management where continuing therapy may prolong
      suffering and postpone death. The question 'Are you doing for the neonate or to
      the neonate?' should be asked. These complex issues, along with best interest
      issues, site, mode and timing of delivery, and the development of palliative care
      are the subject of this manuscript.

PMID- 16625221
TI  - Postdischarge nutritional therapy.
AB  - Nutrient-enriched diets for preterm infants after hospital discharge (preterm
      formula or postdischarge formula (PDF)) results in improved growth and these
      differences appear to persist beyond the period of nutrient intervention. The PDF
      diet effect is greatest in males, possibly reflecting their higher growth rates.
      The critical growth epoch appears to be the first 2 months post-term, suggesting
      a finite period and therefore opportunity for enhanced growth. Whether the
      observed growth effects persist further or have consequences for other aspects of
      health or development requires further investigation.

PMID- 16625223
TI  - Continuous positive airway pressure: early, late, or stay with synchronized
      intermittent mandatory ventilation?
AB  - Mechanical ventilation is associated with significant short- and long-term
      morbidity in small preterm infants. Continuous positive airway pressure applied
      through nasal prongs is an effective, less-invasive method to improve gas
      exchange and reduce apnea in these infants. A large number of studies have
      evaluated the possibility of reducing the need or duration of mechanical
      ventilation by early use of nasal continuous positive airway pressure shortly
      after birth and by applying it after extubation. Although results of these trials
      have not been consistent, most of the evidence suggests that nasal continuous
      positive airway pressure is a viable alternative to mechanical ventilation in
      many preterm infants and that its use after extubation contributes to maintain
      better lung function and reduces apnea. Despite this, there is no evidence that
      these beneficial short-term effects translate into lower rates of long-term
      morbidity such as bronchopulmonary dysplasia and neurologic sequelae or mortality
      rates.

PMID- 16625224
TI  - The clinical impact of high frequency ventilation: review of the Cochrane meta
      analyses.
AB  - Experimental work in animal models suggests that ventilation strategies using
      high frequency oscillatory ventilation or high frequency jet ventilation hold
      great promise in the prevention of lung injury in preterm infants. However,
      clinical trials of either modality demonstrate little clinical benefit and there
      are possibilities of adverse effects, including increased risk of
      intraventricular hemorrhage and poor neurological development.

PMID- 16625225
TI  - Inhaled nitric oxide in term and preterm infants.
AB  - Nitric oxide (NO) is a gas that has potent vasodilator properties. It can be
      administered via inhalation in situations where NO production is impaired and
      results in vasodilatation of the pulmonary capillaries. In term infants, the
      administration of inhaled NO, at a dose of 20 parts per million, may reduce the
      need for extracorporeal membrane oxygenation by reducing pulmonary vascular
      resistance and improving oxygenation. Inhaled NO is an approved therapy in term
      babies with severe hypoxemic respiratory failure. In premature infants, inhaled
      NO may increase bleeding time and decrease platelet aggregation resulting in an
      increased risk for intraventricular hemorrhage. Early administration of inhaled
      NO may also potentially decrease the risk for developing chronic lung disease in
      premature infants. However, since studies show conflicting results, inhaled NO
      should only be used in premature neonates following investigational review board
      approved protocols.

PMID- 16625226
TI  - Surfactant therapy in preterm infants with respiratory distress syndrome and in
      near-term or term newborns with acute RDS.
AB  - Many different surfactant preparations derived from animal sources, as well as
      synthetic surfactants, are available for the treatment of preterm infants with
      respiratory distress syndrome (RDS). Natural, modified surfactants containing
      surfactant-associated proteins appear to be more effective than non-protein
      containing synthetic surfactants. Comparative trials with poractant alfa at a
      higher initial dose of 200 mg/kg appear to be associated with rapid weaning of
      FiO2, less need for additional doses, and decreased mortality in infants <32
      weeks gestation when compared with beractant. Early rescue (<30 min of age)
      surfactant therapy is an effective method to minimize over treatment of some
      preterm infants who may not develop RDS. Surfactant therapy followed by rapid
      extubation to nasal ventilation appears to be more beneficial than continued
      mechanical ventilation. In near-term or term newborns with acute RDS, surfactant
      therapy has been shown to be 70% effective in improving respiratory failure.

PMID- 16625227
TI  - Pulmonary inflammation and bronchopulmonary dysplasia.
AB  - Various pre- and postnatal risk factors, which act additively or synergistically
      induce an injurious inflammatory response in the airways and the pulmonary
      interstitium of preterm infants with bronchopulmonary dysplasia. This
      inflammatory response is characterized by an accumulation of neutrophils and
      macrophages as well as an arsenal of proinflammatory mediators that affect the
      endothelium and alveolar-capillary integrity. Besides proinflammatory cytokines
      and toxic oxygen radicals, lipid mediators as well as potent proteases may be
      responsible for acute lung injury. There is increasing evidence that an imbalance
      between pro- and anti-inflammatory factors, which should protect the alveoli and
      lung tissue, are key features in the pathogenesis of bronchopulmonary dysplasia.
      In addition, a subnormal generation of growth factors may affect alveolarization
      and vascular development in preterm infants with bronchopulmonary dysplasia. In
      this condensed review article, the current concepts on the possible role of
      inflammation in the evolution of bronchopulmonary dysplasia will be summarized.

PMID- 16625228
TI  - Management of hypotension and low systemic blood flow in the very low birth
      weight neonate during the first postnatal week.
AB  - Systemic hypotension during the first postnatal week is associated with increased
      mortality and morbidity in the very low birth weight (VLBW) neonate. Hypotension
      is generally defined as blood pressure below the fifth percentile of the
      gestational- and postnatal-age dependent blood pressure norms. Recent studies
      indicate that in most VLBW neonates, cerebral blood flow autoregulation is indeed
      lost when blood pressure reaches the fifth percentile. Treatment of the
      circulatory compromise should address the primary pathogenic factor(s) of the
      condition (hypovolemia, myocardial compromise, failure of vasoregulation or a
      combination of factors). Recent findings also suggest that vasopressor resistance
      can be treated with a brief course of low-dose hydrocortisone. However, due to
      the short- and potential long-term side effects of early hydrocortisone
      treatment, its use should be restricted to neonates with vasopressor-resistant
      hypotension. Finally, concomitant administration of hydrocortisone with
      indomethacin should be avoided due to the increased incidence of gastrointestinal
      perforations.

PMID- 16625229
TI  - Doppler evaluation of erectile dysfunction - part 2.
AB  - Doppler evaluation in erectile dysfunction (ED) has a significant role in
      determining the cause of ED. The advantages of penile Doppler and pharmacologic
      duplex ultrasonography include objective, minimally invasive evaluation of penile
      hemodynamics at a relatively low cost. Arteriogenic ED may be secondary to
      peripheral vascular disease and diabetes, or may be seen in association with
      coronary artery disease. Various parameters, such as diameter of the cavernosal
      artery, peak systolic flow velocity, degree of arterial dilatation and
      acceleration time, have been suggested for the diagnosis of arteriogenic ED, but
      peak systolic flow velocity is the most accurate indicator of arterial disease.
      This second part of the review article describes the various causes of ED and the
      interpretation and evaluation of color flow Doppler examination in ED.

PMID- 16625230
TI  - Doppler evaluation of erectile dysfunction - part 1.
AB  - Erectile dysfunction (ED) is the consistent inability to achieve and maintain an
      erection sufficient for satisfactory sexual activity. Erectile dysfunction
      affects as many as 30 million men in America, with an increasing prevalence with
      age. Erectile dysfunction is secondary to organic, psychogenic and combined
      causes. The first part of this review article describes the guidelines for
      evaluation and treatment plans for men with ED. It also describes the normal
      sonographic anatomy of the penis, sonographic technique for evaluation of ED and
      the normal phases of erection.

PMID- 16625231
TI  - Salvage of sildenafil failures with cabergoline: a randomized, double-blind,
      placebo-controlled study.
AB  - To evaluate the safety and efficacy of cabergoline in men with erectile
      dysfunction (ED) who did not respond to sildenafil. Four hundred two sildenafil
      nonresponders aged from 21 to 59 years were included in the study. Patients were
      randomly divided into group 1, those who received 0.5-1 mg cabergoline weekly for
      6 months and group 2, who received placebo for the same period. They underwent
      preliminary assessment, including medical and sexual history, self-administered
      International Index of Erectile Function (IIEF) and intravaginal ejaculatory
      latency time (IVELT) evaluation. Standard biochemistry and hematological
      laboratory tests, and measurement of serum testosterone and prolactin levels were
      also carried out. When indicated, other tests were used to establish the
      diagnosis of vasculogenic and neurogenic ED, including penile color duplex
      Doppler ultrasonography, pudendal nerve conduction test and impaired sensory
      evoked potentials studies. The efficacy of two treatments was assessed every 2
      weeks during treatment, at the end of the study, using responses to IIEF, IVELT
      evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and
      adverse drug effects. The trial was completed by 370 (92%) men. Positive clinical
      results were seen in 31.2% of patients in the cabergoline group compared with
      7.1% of patients in the placebo group (P=0.04). The mean weekly intercourse
      episodes increased from pretreatment values of 1.4 and 1.2 to 2.2 and 1.4, for
      cabergoline and placebo, respectively (P=0.04). Baseline mean intercourse
      satisfaction domain values of IIEF 10 and 11 reached to 15 and 10 at 6-month
      treatment in groups 1 and 2, respectively (P=0.04). The IVELT after cabergoline
      and placebo gradually increased from 98 and 101 s to approximately 242 and 116 s,
      respectively (P=0.001). More drug-related adverse effects occurred in cabergoline
      group and 12 (5.9%) had to discontinue treatment (P=0.001). Cabergoline is
      moderately effective salvage therapy for sildenafil nonresponse. Further studies
      with different dosages and treatment regimens are necessary to draw final
      conclusions on the efficacy of this drug in ED.

PMID- 16625232
TI  - Diagnostic value of nitric oxide, lipoprotein(a), and malondialdehyde levels in
      the peripheral venous and cavernous blood of diabetics with erectile dysfunction.
AB  - Diabetes mellitus (DM) is the single most common cause of erectile dysfunction
      (ED) seen in clinical practice. Evaluation of penile arterial insufficiency in
      diabetic patients currently entails expensive and invasive testing. We assessed
      the diagnostic value of certain peripheral and cavernous blood markers as
      predictors of penile arterial insufficiency in diabetic men with ED. This study
      was conducted on a total of 51 subjects in three groups: 26 impotent diabetics,
      15 psychogenic impotent men and 10 normal age matched control males. All subjects
      underwent standard ED evaluation including estimation of postprandial blood sugar
      and serum lipid profile. Peripheral venous levels of nitric oxide (NO),
      lipoprotein(a) (LP(a)), malondialdehyde (MDA) and glycosylated hemoglobin (HbA1c)
      were obtained in all subjects. Patients in the two impotent groups underwent
      additional measurement of NO, LP(a) and MDA levels in cavernous blood. They also
      underwent intracavernosal injection (ICI) of a trimix (papaverine, prostaglandin
      E1 and phentolamine mixture) and pharmaco-penile duplex ultrasonography (PPDU).
      Compared to patients in the psychogenic group, diabetic men had significantly
      lower erectile response to ICI (P<0.001), lower peak systolic velocity (PSV)
      (P<0.001), and smaller increase in cavernosal artery diameter (CAD) (P<0.001).
      Peripheral and cavernous levels of both LP(a) and MDA were higher in the diabetic
      group as compared to the psychogenic ED group (P<0.001), while the values of
      peripheral venous and cavernous NO were lower (P<0.001) in the diabetic men.
      Comparison of biochemical marker assays with the PPDU results showed a
      significant negative correlation between both venous and cavernous LP(a) and MDA
      levels on the one hand, and PSV, and the percentage of CAD increase on the other.
      At the same time, peripheral and cavernous NO levels had a significant positive
      correlation with the same parameters. Lipoprotein(a), MDA and NO levels were
      better predictors of low PSV than HbA1c, cholesterol or triglyceride levels. The
      finding of high levels of LP(a) and MDA with low levels of NO in the peripheral
      and cavernous venous blood of diabetic men with ED correlates strongly with
      severity of ED as measured by PPDU. This provides a rationale for further studies
      of biochemical markers as a surrogate for traditional invasive testing in the
      diagnosis of penile arterial insufficiency.

PMID- 16625233
TI  - Association between the Pro12Ala variant of the peroxisome proliferator-activated
      receptor-gamma2 gene and increased 24-h diastolic blood pressure in obese
      patients with type II diabetes.
AB  - The aim of the study was to examine an association between the Pro12Ala
      polymorphism of the peroxisome proliferator-activated receptor (PPAR)-gamma2 gene
      and blood pressure values assessed by 24-h ambulatory blood pressure monitoring
      (ABPM) in obese patients with long-lasting type II diabetes. Two hundred and
      fourteen obese patients (95 men and 119 women) with above 10-year history of type
      II diabetes were recruited for the study. In all the patients, ABPM was performed
      and other parameters, including age, body mass index (BMI), waist/hip ratio
      (WHR), haemoglobin A1c (HbA(1c)), serum lipids and creatinine were also
      evaluated. The Pro12Ala polymorphism was analysed by polymerase chain reaction
      restriction fragment length polymorphism. Two subgroups of patients were
      compared: (a) Pro/Pro: homozygotic Pro/Pro (n=154) and (b) Ala: Ala allele
      carriers (Ala/Ala+Ala/Pro) (n=60). The studied groups were not different when
      age, BMI, WHR, HbA(1c), lipids, creatinine and frequency of hypertension were
      compared. A similar ratio of patients from both groups were treated with
      angiotensin-converting enzyme inhibitors, calcium channel blockers, diuretics,
      beta-blockers and alpha-blockers. A difference was observed in a mean 24-h (Ala:
      71.9+/-8.1 vs Pro/Pro: 69.4+/-7.8 mm Hg, P=0.034) and a mean night time (Ala:
      67.1+/-7.8 vs Pro/Pro: 64.5+/-8.4 mm Hg, P=0.025) diastolic blood pressure, which
      was significantly higher in patients with Ala variant. There was also a trend
      towards a higher mean daytime diastolic blood pressure in this group. It seems
      that the Pro12Ala variant is associated with an increased mean 24-h diastolic
      blood pressure in obese diabetic patients. Different reaction for
      antihypertensive medication depending on a variant of the PPAR-gamma2 gene should
      also be considered as a possible cause of the presented results.

PMID- 16625234
TI  - Effect of pravastatin on blood pressure in people with cardiovascular disease.
AB  - Experimental evidence and several small studies in humans suggest that HMG-CoA (3
      hydroxy 3-methylglutaryl coenzyme A) reductase inhibitors (statins) reduce blood
      pressure, perhaps through effects on endothelial function or by reducing
      inflammation. We tested the hypothesis that pravastatin would reduce blood
      pressure at 3 months and the risk of developing new hypertension over a follow-up
      period of 5 years. This was a post hoc subgroup analysis of a randomized double
      blind placebo-controlled trial of pravastatin 40 mg daily vs placebo in 4159
      participants with previous myocardial infarction and total plasma cholesterol
      <240 mg/dl (6.2 mmol/l). The primary outcome was the unadjusted change in mean
      arterial pressure (MAP) from baseline to 3 months. We also considered systolic
      and diastolic blood pressure (SBP and DBP) and pulse pressure. Analysis of
      covariance was used to calculate the adjusted effect of treatment on change in
      these outcomes at 3, 6, 12 and 24 months postrandomization, after controlling for
      potential confounders. Logistic regression was used to calculate the adjusted
      effect of treatment on incident hypertension (blood pressure > or =140/90 in
      those without known hypertension at baseline). This analysis included 4126/4159
      (99.2%) participants for whom blood pressure was measured at baseline and during
      at least one follow-up visit. Median duration of follow-up was 57.8 months. The
      unadjusted and adjusted change in MAP, SBP, DBP or pulse pressure from baseline
      was not significantly different for pravastatin or placebo recipients at 3, 6, 12
      or 24 months after randomization, or at last follow-up. Pravastatin did not
      reduce the adjusted risk of incident systolic hypertension (odds ratio 0.99, 95%
      CI 0.80-1.23), or incident diastolic hypertension (odds ratio 0.97, 95% CI 0.73
      1.27). In summary, pravastatin 40 mg daily did not reduce blood pressure in
      survivors of myocardial infarction without overt hypercholesterolaemia.

PMID- 16625235
TI  - Impact of moderate overweight and body composition on postexercise hemodynamic
      responses in healthy men.
AB  - Postexercise hypotension (PEH) is a well-established phenomenon that may
      contribute to the antihypertensive mechanisms of exercise. The purpose of this
      study was to examine the impact of moderate overweight on postexercise
      hemodynamic responses in a group of healthy nonobese men (n = 16, aged 20.4+/-1.8
      years) with apparently normal cardiovascular function at rest. Forearm blood
      flow, using strain gauge plethysmography, blood pressure, using a Finapres
      device, and cardiac output (CO), using impedance cardiography, were measured on a
      control day and on a separate day following a bout of moderate intensity exercise
      (20 min at 75% heart rate reserve). Linear regression analysis, adjusted for
      exercise intensity, revealed that body mass index (BMI) was associated with
      specific postexercise hemodynamic responses. Higher BMI was associated with
      greater reductions in CO and stroke volume, but lower reductions in total
      peripheral resistance. These findings suggest body composition impacts on
      mechanisms of PEH and should therefore be considered as an important confounding
      variable in future studies.

PMID- 16625236
TI  - Nitric oxide and cell adhesion molecules in essential hypertension: a case
      control study.

PMID- 16625237
TI  - Plasma adrenomedullin level and development of hypertension.
AB  - The hypotensive peptide adrenomedullin (AM) is assumed to act as a factor
      inhibitory on elevation of blood pressure and on progression of the hypertensive
      organ damage, and plasma AM levels are elevated in patients with hypertension.
      The aim of the present study is to explore whether or not a rise in plasma AM
      levels precedes the development of hypertension. Normotensive local residents
      without apparent cardiovascular or renal disease (n = 177) were divided into low
      and high AM groups based on the median concentration of AM in plasma (11.9
      fmol/ml), and followed up for 3 years for development of hypertension. The
      incidence of hypertension was higher in the residents with high AM than low AM
      levels (27.8 vs 11.5%, P < 0.01), whereas a similar analysis of plasma levels of
      atrial or brain natriuretic peptides revealed no such difference. The plasma AM
      level was found to be a significant parameter for the development of hypertension
      in a univariate analysis (P < 0.01), but not in a multivariate analysis.
      Meanwhile, the plasma AM level was significantly (P < 0.01) correlated with age
      and body mass index (BMI), two variables independently significant for the
      development of hypertension. The present findings suggest that an elevation of
      the plasma AM level associated with aging and increased BMI precedes the
      development of hypertension in the normotensive subjects.

PMID- 16625238
TI  - Effect of cilnidipine on left ventricular function in hypertensive patients as
      assessed by tissue Doppler Tei index.
AB  - Tissue Doppler Tei index is pointed to be more effective in the evaluation of
      global cardiac function than systolic and diastolic measurements alone in various
      heart diseases. This study was designed to assess the effect of cilnidipine on
      left ventricular function in hypertensive patients by using this index. A group
      of 40 hypertensives (mean age 55+/-8 years, range: 35-65) and 16 controls (mean
      age 52+/-9 years, range: 36-65) were included. Hypertensives were classified into
      non-left ventricular hypertrophy (NLVH) group (25 patients) and left ventricular
      hypertrophy (LVH) group (15 patients), and treated with cilnidipine for 2 months.
      Before and after treatment, the participants were examined by echocardiography.
      Tissue Doppler Tei index was calculated as diastolic time interval measured from
      end of late diastole to origin of early diastole (a') minus systolic Sm duration
      (b') divided by b', that is Tei index = (a'-b')/b'. Thirty-seven hypertensive
      patients finished the treatment. Tei index was significantly higher in NLVH and
      LVH groups than in control group, and in LVH group than in NLVH group (0.44+/
      0.07 vs 0.28+/-0.06, P < 0.001; 0.51+/-0.13 vs 0.28+/-0.06, P < 0.001; 0.51+/
      0.13 vs 0.44+/-0.07, P < 0.05). After treatment, Tei index was significantly
      decreased (0.40+/-0.11 vs 0.46+/-0.10, P < 0.0001); systolic blood pressure and
      diastolic blood pressure were also decreased significantly. In conclusion, Tei
      index is impaired in hypertensives before development of ventricular hypertrophy
      and impairment is more prominent in hypertrophy. Cilnidipine can improve left
      ventricular function. Tissue Doppler Tei index is gaining importance in
      evaluating LV function after drug intervention in hypertensive patients.

PMID- 16625239
TI  - Change in circadian rhythm of blood pressure by bilateral radical nephrectomy and
      haemodialysis: a case report.

PMID- 16625240
TI  - Arterial compliance: is it reduced in antiphospholipid syndrome?
AB  - To assess vascular compliance in patients with antiphospholipid syndrome (APS),
      or antiphospholipid antibodies (aPLs) positivity in comparison to healthy people
      and diabetes mellitus patients. Twenty-five patients with APS or aPLs, 33 healthy
      people (HP), 28 patients with diabetes mellitus (DM) underwent pulse wave
      analysis. Data calculated included the small artery elasticity (SAE), large
      artery elasticity (LAE) and systemic vascular resistance (SVR). Statistical
      analysis was performed as appropriate. The patient group was divided into two
      subgroups: APS-1 with warfarin treatment, and APS-2 without warfarin treatment.
      All patients and healthy subjects were matched by gender, body mass index and
      lipid profiles. Patients in APS-1 group were significantly younger in comparison
      to three other groups. After the adjustment for age, we found that SAE in APS-1
      group did not differ from SAE in the HP group (6.4+/-1.8 ml/mmHg x 100 and 5.54+/
      3.4 ml/mmHg x 100, respectively, P>0.05). In contrast, SAE in the group APS-2 was
      significantly lower (3.41+/-1.2 ml/mmHg x 100) than in the APS-1 and was almost
      equal to SAE in the DM group (4.2+/-2.37 ml/mmHg x 100). The SAE in the APS-2, DM
      and HP groups was inversely correlated with age, whereas in the APS-1 group we
      did not find such correlation. This pilot study showed abnormal small vascular
      elasticity in the patients with positive aPL, relative to the healthy subjects.
      The APS patients, treated with warfarin had the normal vascular function. This
      data support the hypothesis that APS may be associated with diffuse changes in
      the arterial wall, and may be a risk factor for atherosclerotic disease.

PMID- 16625241
TI  - A newly modified SCG10 promoter and Cre/loxP-mediated gene amplification system
      achieve highly specific neuronal expression in animal brains.
AB  - We designed a new promoter that drives transgene expression in an exclusively
      neuron-specific manner. The promoter of superior cervical ganglion10 (SCG10),
      expressed in neurons, was further modified to enhance its neuron specificity and
      activity by changing its length and fusing a multiple neuronal restrictive
      silencer element (NRSE) to its upstream or downstream regions. The promoter,
      which contained 2 kb original promoter length and two extra NRSEs in its
      downstream region, eventually exhibited remarkable neuron specificity as well as
      strong activity. To further amplify the promoter activity, the promoter was
      introduced into a Cre recombinase (Cre)-expressing adenovirus, and subsequent
      combination with Cre-inducible enhanced green fluorescence protein (EGFP)
      expressing adenovirus vector, which has much stronger general promoter, resulted
      in a remarkably strong gene expression exclusively in neuronal cells of mixed
      cultures and in an animal model. This system is also applicable to astrocyte
      specific expression; for instance, by changing the Cre promoter cassette to an
      astrocyte-specific promoter. The present relatively compact promoter combined
      with Cre/loxP system could be useful for a wide range of transgene experiments in
      vivo as well as for clinical applications.

PMID- 16625242
TI  - RNA interference in the mouse vascular endothelium by systemic administration of
      siRNA-lipoplexes for cancer therapy.
AB  - RNA interference (RNAi) entails the potential for novel therapeutic strategies
      through the silencing of disease-causing genes in vivo. However, recent studies
      have raised an issue regarding applicable routes of administration for small
      interfering RNA (siRNA) molecules as therapeutics. In this study, we demonstrate
      that liposomally formulated siRNA molecules, the so-called siRNA-lipoplexes, but
      not naked siRNAs, are delivered to the tumor endothelial cells in vivo by
      microscopy. In addition, functional intracellular delivery of formulated siRNA
      targeting the tumor suppressor PTEN is shown in endothelial cells of the liver
      and tumor. Finally, the therapeutic potential of systemically administered
      siRNA(CD31)-lipoplexes is established by inhibition of tumor growth in two
      different xenograft mouse models. Our findings corroborate the applicability of
      this liposomal siRNA delivery technology for inducing RNAi to modulate gene
      expression levels in angiogenesis-dependent processes. In addition, our results
      advocate CD31 as a promising therapeutic target for antiangiogenic intervention.
      Therefore, our study provides a basis for the development of antiangiogenic
      cancer therapies based on RNAi.

PMID- 16625243
TI  - A novel siRNA-lipoplex technology for RNA interference in the mouse vascular
      endothelium.
AB  - For the application of RNA interference (RNAi) in vivo the functional delivery of
      short interfering RNAs (siRNAs) is still the major obstacle. Therefore, delivery
      technologies need to be established for the systemic application of RNAi in vivo.
      Here we report uptake, biodistribution and in vivo efficacy of siRNA molecules
      formulated into siRNA-lipoplexes. The applied formulation is based on complex
      formation of positively charged liposomes, a mixture of cationic and fusogenic
      lipids complexed with the negatively charged siRNA. We determined by fluorescence
      microscopy the temporal and spatial distribution of fluorescently labeled siRNA
      lipoplexes, the body clearance and endothelial cell type specific uptake after
      single intravenous injection. Furthermore, by using siRNA molecules for targeting
      endothelia-specifically expressed genes, such as CD31 and Tie2, we were able to
      demonstrate downregulation of the corresponding mRNA and protein in vivo. Taken
      together, we show the applicability of this non-viral delivery technology for
      inducing RNAi in the vasculature of mice after systemic application.

PMID- 16625244
TI  - Angiogenic and antifibrotic actions of hepatocyte growth factor improve cardiac
      dysfunction in porcine ischemic cardiomyopathy.
AB  - Impairment of cardiac function in ischemic cardiomyopathy has been postulated to
      be due to the decrease in blood flow and increase in collagen synthesis.
      Therefore, an approach to alter them directly by means of a growth factor may
      open up a new therapeutic concept in ischemic cardiomyopathy. From this
      viewpoint, hepatocyte growth factor (HGF) is a unique growth factor with
      angiogenic and antifibrotic effects. Thus, we examined the feasibility of gene
      therapy using HGF plasmid DNA for ischemic cardiomyopathy. Human HGF plasmid DNA
      at a dose of 0.4 or 4 mg was injected into ischemic myocardium of pigs induced by
      ameroid constrictor with the NOGA system. At 1 month after injection, the
      ischemic area was significantly reduced in the HGF group, accompanied by a
      significant increase in capillary density and regional myocardial perfusion in
      the ischemic area (P<0.01). In contrast, a significant decrease in fibrotic area
      was observed in the HGF group, associated with a significant decrease in collagen
      I, III and TGF-beta synthesis as compared to the control group (P<0.01).
      Consistently, cardiac function was significantly improved in the 4 mg HGF group
      as compared to the control group (P<0.05). Overall, the present in vivo
      experiments demonstrated that intramyocardial injection of human HGF plasmid DNA
      in ischemic cardiomyopathy resulted in a significant improvement in cardiac
      function through an increase in blood flow and decrease in fibrosis. These
      favorable outcomes suggest potential utility to treat patients with ischemic
      heart disease using HGF gene transfer. Currently, a phase I study using human HGF
      plasmid DNA is ongoing to test the validity of this concept.

PMID- 16625246
TI  - Nesting of fullerenes and Frank-Kasper polyhedra.
AB  - The duality relationship between fullerenes and Frank-Kasper polyhedra suggests
      that these two families of polyhedra appear nested in solid state structures.
      Magic numbers, described by simple mathematical relationships, identify four
      families of fullerenes with tetrahedral and icosahedral symmetries.

PMID- 16625245
TI  - The perforin-dependent immunological synapse allows T-cell activation-dependent
      tumor targeting by MLV vector particles.
AB  - We have reported that retroviral particles adhered to the surface of antigen
      specific T cells can be carried to metastases following adoptive transfer in
      vivo, a process we have called viral hitch hiking. Following antigen-driven T
      cell accumulation at tumors, viral particles productively infect tumor cells via
      envelope/receptor dependent interactions ('hand on' of virus from the T cell to
      the tumor cell). We describe here a second envelope/receptor independent pathway
      of viral hand on from T cells, dependent on T-cell activation. We show that the
      endosomolytic property of perforin promotes release of viral particles from
      endosomes into which they are co-delivered along with cytotoxic granules from the
      activated T cell. Therefore, hand on of MLV particles lacking any envelope can be
      used for in vivo delivery of vectors, where targeting is at the extremely
      specific level of recognition of antigen by the T-cell receptor, thereby
      dispensing with the need to engineer viral envelopes. These data reveal a novel
      pathway by which MLV viral particles exploit a functional immunological synapse
      and present new opportunities both to improve the efficacy of adoptive T-cell
      transfer and to target vectors for systemic gene delivery.

PMID- 16625247
TI  - The effect of P-cyclohexyl groups on the coordination chemistry of
      phosphaguanidinates.
AB  - The anion of P-dicyclohexylphosphaguanidine, Cy2PC{NiPr}{NHiPr}, forms a P,N
      chelate at lithium and cobalt(II); bridging through the Nimine atom forms cyclic
      hexamers in the former complex.

PMID- 16625248
TI  - A scandium coordination polymer constructed from trimeric octahedral building
      blocks and 2,5-dihydroxyterephthalate.
AB  - Scandium chloride and nitrate react with 2,5-dihydroxyterephthalic acid to form
      three-dimensional framework compounds in which hexagonally-closed packed
      inorganic building blocks are linked by the carboxylate groups of the organic
      ligand. The inorganic moieties consist of three scandium oxygen octahedra that
      are joined by a common mu3-oxygen atom; the pores in the structure account for
      60% of the volume, but the framework decomposes upon removal of the solvent
      molecules.

PMID- 16625249
TI  - Chiral spiro Cu(I) complexes. Supramolecular stereocontrol and isomerisation
      dynamics by the use of TRISPHAT anions.
AB  - Association of enantiopure TRISPHAT anion (1) with chiral spiro [Cu(LL')2]
      complexes (LL' = 2-R-phen, 2, 6-R-bpy, 3, and 2-iminopyridine, 4) leads to an
      efficient NMR enantiodifferentiation. Variable temperature 1H NMR spectroscopy
      has been used to determine the isomerisation kinetics of these pseudo-tetrahedral
      complexes and to evaluate their configurational stability; the latter depending
      on the structure of the diimine ligands. In the case of the 2-anthracenyl-phen
      derivative, a decent level of supramolecular stereocontrol was noted (d.e. up to
      45%); the configuration of the complex being determined by electronic circular
      dichroism (ECD).

PMID- 16625250
TI  - Double-strand DNA cleavage by copper complexes of 2,2'-dipyridyl with
      electropositive pendants.
AB  - Two highly charged cationic copper(II) complexes have been synthesized and
      characterized structurally and spectroscopically: [Cu(L1)2(Br)](ClO4)5 (1) and
      [Cu(L2)2(Br)](ClO4)5 (2) (L1= 5,5'-di(1-(triethylammonio)methyl)-2,2'-dipyridyl
      cation and L2= 5,5'-di(1-(tributylammonio)methyl)-2,2'-dipyridyl cation bidentate
      ligands). X-Ray structures show that Cu(II) ions in both complexes have a
      trigonal-bipyramidal CuN4Br-configuration. Two nitrogen atoms of the
      electropositive pendants and coordinated bromine atom basically array in a
      straight line. Their close distances of N[dot dot dot]Br atoms are 5.772 and
      5.594 A, respectively, which is comparable to that of adjacent phosphodiesters in
      B-form DNA (ca. 6 A). In the absence of reducing agent, supercoiled plasmid DNA
      cleavage by the complexes has been performed and their hydrolytic mechanisms have
      been investigated. The pseudo-Michaelis-Menten kinetic parameters (kcat), 4.15 h(
      1) for 1, 0.43 h(-1) for 2 and 0.61 h(-1) for [Cu(bipy)(NO3)2], were obtained.
      This result indicates that 1 exhibits markedly higher nuclease activity than its
      corresponding analogues. The high ability of DNA cleavage for 1 is attributed to
      the effective cooperation of the metal moiety and two positive pendants since the
      array of linear tri-binding sites matches with one of three phosphodiester
      backbones of nucleic acid.

PMID- 16625251
TI  - Contrasting photochemical and thermal reactivity of Ru(CO)2(PPh3)(dppe) towards
      hydrogen rationalised by parahydrogen NMR and DFT studies.
AB  - The synthesis, characterisation and thermal and photochemical reactivity of
      Ru(CO)2(PPh3)(dppe) 1 towards hydrogen are described. Compound proved to exist in
      both fac (major) and mer forms in solution. Under thermal conditions, PPh3 is
      lost from 1 in the major reaction pathway and the known complex Ru(CO)2(dppe)(H)2
      2 is formed. Photochemically, CO loss is the dominant process, leading to the
      alternative dihydride Ru(CO)(PPh3)(dppe)(H)2 3. The major isomer of 3, viz. 3a,
      contains hydride ligands that are trans to CO and trans to one of the phosphorus
      atoms of the dppe ligand but a second isomer, 3b, where both hydride ligands are
      trans to distinct phosphines, is also formed. On the NMR timescale, no
      interconversion of 3a and 3b was observed, although hydride site interchange is
      evident with activation parameters of DeltaH(double dagger) = 95 +/- 6 kJ mol(-1)
      and DeltaS(double dagger) = 26 +/- 17 J K(-1) mol(-1). Density functional theory
      confirms that the observed species are the most stable isomeric forms, and
      suggests that hydride exchange occurs via a transition state featuring an eta2
      coordinated H2 unit.

PMID- 16625252
TI  - Hydrogen-bond tuning of ferromagnetic interactions: synthesis, structure and
      magnetic properties of polynuclear copper(II) complexes incorporating p-block oxo
      anions.
AB  - The reaction of copper(II) hydroxide with 2,2'-bipyridine (bipy) (1 : 1) in
      alkaline aqueous solution (pH 14) at room temperature affords the alternating
      carbonate/hydroxo-bridged copper(II) polymeric chain compound {[Cu3(bipy)3(mu
      OH)2(mu-CO3)2].11H2O}n, 1, as determined by single-crystal X-ray diffraction. The
      structure of 1 is built up from two similar centro-symmetric dinuclear
      [(bipy)Cu(mu-OH)]2 cores which link together via bridging carbonate groups to
      mononuclear [(bipy)Cu] fragments to form the chain. Interdigitation of adjacent
      chains through pi-pi interactions, which involve each bipy ligand, forms sheets
      that are separated by the water molecules of crystallisation. Variable
      temperature magnetic susceptibility measurements have shown that 1 behaves as an
      isolated spin doublet with two non-interacting spin triplets with the magnetic
      coupling through the bis-mu-hydroxo bridges being strongly ferromagnetic in
      nature. The hydrothermal reaction of copper(II) hydroxide, bipy and ammonium
      hydrogenphosphate (pH 8) yields a dinuclear copper(II) complex of formula
      {[Cu2(bipy)2(mu-OH)2(HPO4)(H2O)].4H2O}, 2, as determined by single-crystal X-ray
      diffraction. The structure of consists of an asymmetric dinuclear bis-mu-hydroxo
      copper(II) core with a monodentate hydrogenphosphate dianion coordinating to one
      copper(II) atom (above) and a water molecule to the other (below). Intra- and
      inter-molecular hydrogen bond interactions involving the hydrogenphosphate, water
      molecules and bis-mu-hydroxo groups link adjacent dinuclear fragments into
      chains, which interdigitate to form sheets that are separated by the water
      molecules of crystallisation. The investigation of the magnetic properties of 2
      showed that the strength of the ferromagnetic interaction through the bis-mu
      hydroxo bridges is influenced by the significant out-of-plane displacement of the
      hydrogen atom of the hydroxo groups, brought about through hydrogen bonding to
      the hydrogenphosphate ligand, and yielded the strongest ferromagnetic coupling
      yet reported for the bis-mu-hydroxo copper(II) core.

PMID- 16625253
TI  - Neutral and cationic aluminium complexes of a sterically demanding N
      imidoylamidine ligand.
AB  - The N-imidoylamidine ligand i-Pr2C6H3N(C(Me)NC6H3i-Pr2)2 2 was prepared. Direct
      reactions with AlI3 or AlMe3 afforded [(i-Pr2C6H3N(C(Me)NC6H3i-Pr2)2)AlI2][AlI4]
      3 and [i-Pr2C6H3N(C(Me)NC6H3i-Pr2)2)AlMe2][AlMe4].AlMe3, 4 respectively.
      Thermolysis of 4 gave (i-Pr2C6H3NC(=CH2)(NC6H3i-Pr2)(C(Me)NC6H3i-Pr2)AlMe2 6.
      Subsequent reaction with B(C6F5)3 gave the zwitterionic species [(i
      Pr2C6H3)N(C(=CH2)NC6H3i-Pr2)(C(Me)NC6H3i-Pr2)AlMe(mu-MeB(C6F5)3)] 7. In a related
      reactions of 2, [Ph3C][B(C6F5)4] and AlMe3, AlH3.NEtMe2 or AlD3.NMe3, the
      complexes [(i-Pr2C6H3N(C(Me)NC6H3i-Pr2)2)AlR2][B(C6F5)4] (R = Me 5, H 8, D 9) and
      [(i-Pr2C6H3)N(C(=CH2)NC6H3i-Pr2)(C(Me)NC6H3i-Pr2)AlH][B(C6F5)4] 10 are formed.
      Single-crystal X-ray data for 2, 3, 5 and 10 are reported.

PMID- 16625254
TI  - A general one-pot synthesis for elusive 2-substituted indenes: does bis[2-(tert
      butyl)indenyl]zirconium(IV) dichloride/MAO polymerise ethene?
AB  - Among the 2-substituted indenes, 2-trifluoroindene and 2-tert-butylindene are
      poorly or incompletely described in the open literature. We herein describe an
      efficient one-pot synthesis of these compounds as a variation of the Perkin
      reaction which allows us to refute an earlier claim that bis(2-tert
      butylindenyl)zirconium(IV) dichloride (2a) will not polymerise ethene. In fact,
      2a/MAO polymerises ethene to extremely high molecular weights. Extensive DFT
      calculations on the polymerisation mechanism revealed an unprecedented
      suppression of the otherwise predominant chain termination by beta-hydride
      transfer due to steric congestion of the active site.

PMID- 16625255
TI  - Novel linear hexanuclear cobalt string complexes (Co6(12+)) and one-electron
      reduction products (Co6(11+)) supported by four bpyany2- ligands.
AB  - The new ligand, 2,7-bis(alpha-pyridylamino)-1,8-naphthyridine (H2bpyany), was
      synthesized by the reaction of 2,7-dichloro-1,8-naphthyridine with 2
      aminopyridine in the presence of t-BuOK under palladium(0)-catalyzed conditions.
      The preparation and characterization of novel hexacobalt string complexes,
      [Co6(mu6-bpyany)4(NCS)2](PF6)n (n=1 (1); n=2 (2)) and [Co6(mu6
      bpyany)4(OTf)2](OTf)n (n = 2 (3); n = 1 (4)) are presented. The crystal
      structures for compounds have been determined by X-ray crystallography. Compounds
      1 and 4 have the Co6 11+ configurations and are air-stable. Compounds 2 and 3
      with Co6 12+ configurations are structurally similar to 1 and 4, respectively.
      The electrochemistry of 1 displays four redox couples at E1/2= -0.55, +0.38,
      +0.91, and +1.18 V (vs. Ag/AgCl). The magnetic data show that compounds 1 and 4
      are in a spin state of S = 1/2, and 2 and 3 in a spin state of S = 1. The results
      of the EHMO calculations on compounds 1 and 2 are in agreement with their
      magnetic measurements.

PMID- 16625256
TI  - Preparation and characterization of dinuclear Pd(II) complexes of binucleating
      tetraaza-thiophenolate ligands.
AB  - The thioethers 4-tert-butyl-2,6-bis((2
      (dimethylamino)ethylimino)methyl)phenyl(tert-butyl)sulfane (tBu-L3) and 4-tert
      butyl-2,6-bis((2-(dimethylamino)ethylimino)methyl)phenyl(tert-butyl)sulfane (tBu
      L4) react with PdCl2(NCMe)2 to give the dinuclear palladium thiophenolate
      complexes [(L3)Pd2Cl2]+ (2) and [(L4Pd2(mu-Cl)]2+ (3) (HL3= 2,6-bis((2
      (dimethylamino)ethylimino)methyl)-4-tert-butylbenzenethiol, HL4 = 2,6-bis((2
      (dimethylamino)ethylamino)methyl)-4-tert-butylbenzenethiol). The chloride ligands
      in could be replaced by neutral (NCMe) and anionic ligands (NCS-, N3-, CN-, OAc-)
      to give the diamagnetic Pd(II) complexes [(L3)Pd2(NCMe)2]3+ (4), [(L3)Pd2(NCS)2]+
      (5), [(L3)Pd2(N3)2]+ (6), [{(L3)Pd2(mu-CN)}2]4+ (7) and [(L3)Pd2(OAc)]2+ (9). The
      nitrile ligands in and in [(L3)Pd2(NCCH2Cl)2]3+ are readily hydrated to give the
      corresponding amidato complexes [(L3)Pd2(CH3CONH)]2+ (8) and
      [(L3)Pd2(CH2ClCONH)]2+ (10). The reaction of [(L3)Pd2(NCMe)2]3+ with NaBPh4 gave
      the diphenyl complex [(L3)Pd2(Ph)2]+ (11). All complexes were either isolated as
      perchlorate or tetraphenylborate salts and studied by IR, 1H and 13C NMR
      spectroscopy. In addition, complexes 2[ClO4], 3[ClO4]2, 5[BPh4], 6[BPh4],
      7[ClO4]4, 9[ClO4]2, 10[ClO4]2 and 11[BPh4] have been characterized by X-ray
      crystallography.

PMID- 16625257
TI  - Syntheses, structures, luminescence and electrochemistry of benzene- and biphenyl
      centered bis- and tris-1,3,2-diazaboroles and -1,3,2-diazaborolidines.
AB  - Reaction of 1,4-bis(dibromoboryl)benzene (1a) with 2 equiv. of the diazabutadiene
      tBuN=CH-CH=NtBu and subsequent reduction of the obtained bis(1,3,2
      diazaborolium)salt 2a with sodium amalgam afforded the 1,4-bis(1,3,2
      diazaborolyl)benzene 3a. Similarly, 1,3-bis(dibromoboryl)benzene (1b), 1,3,5
      tris(dibromoboryl)benzene (1c) and 4,4'-bis(dibromoboryl)biphenyl (1d) were
      converted into compounds 3b, 3c and 3d which contain two or three diazaborolyl
      substituents at the arene core. Treatment of precursors 1a,b,d with two equiv. or
      with three equiv. of N,N'-di-tert-butylethane-1,2-diamine in the presence of an
      excess of NEt3 gave rise to the diazaborolidine derivatives 4a-4d. Reaction of
      1,3-bis(diiodoboryl)benzene with two equivalents of N,N'-dimethylethane-1,2
      diamine in the presence of NEt3 furnished the corresponding 1,3
      bis(diazaborolidinyl)benzene 4e. The novel compounds were characterized by
      elemental analyses and spectroscopy (1H, 13C, 11B NMR, MS). The molecular
      structures of 3c, 4a and 4e were eludicated by X-ray-diffraction analyses. In
      addition to this, the oxidative cyclovoltammograms and blue emission spectra of
      these novel compounds were discussed. Here, the electronic communication between
      boron heterocycles on the different spacer-units and the luminescence of the
      oligo-diazaborolylarenes were of interest.

PMID- 16625258
TI  - Pentahapto-bonded gold heteroborane clusters [3-(R3P)-closo-2,1-AuTeB10H10]- and
      [3-(R3P)-closo-3,1,2-AuAs2B9H9]-.
AB  - Gold acetylide compounds [(R3P)AuC[triple bond]CC(Me)(OH)Et], where R = Ph 1 or
      cyclohexyl (Cy) 2, were synthesised and 2 was characterised using X-ray
      diffraction techniques. The solid-state structure of 2 contained a two-coordinate
      gold atom and a linear P-Au-C[triple bond]C-C bonding sequence. The reactions
      between 1 or 2 and [NR4][nido-7,8-As2B9H10] or [NR4][nido-7-TeB10H10] in ethanol
      acetone solvent afforded the twelve-vertex cluster species [NMe4][3-(R3P)-closo
      3,1,2-AuAs2B9H9], where R = Ph 5 or Cy 6, or [NEt4][3-(R3P)-closo-2,1
      AuTeB10H10], where R = Ph 7 or Cy 8, in moderate or low yields (ca. 35% for , and
      and ca. 20% for ). Compounds and were characterised with X-ray crystallographic
      techniques. Although there was crystallographic disorder in the {As2B3} and
      {TeB4} rings to which the gold atoms were attached, the structures of 5 and 7
      strongly suggested that the gold atoms were pentahapto bonded to all the atoms in
      the {As2B3} or {TeB4} rings giving formally closo cluster geometries with closo
      cluster electron counts. The solution-phase NMR properties of 5, 6 and 7 were
      consistent with closo descriptions.

PMID- 16625259
TI  - Sterically encumbered acyclic diphosphazanes: synthesis, conformations and
      coordination behavior.
AB  - The reaction between lambda3-diphosphazane [EtN(PCl2)2] and the sodium salts of
      substituted phenols affords sterically encumbered diphosphazanes [EtN{P(OR)2}2]
      (R = -C6H3iPr2-2,6 (1), -C6H3Me2-2,6 (2) and -C6H2Me3-2,4,6 (3)). When the same
      reaction was carried out with bulky sodium 2,4-di-tert-butyl-4-methylphenoxide,
      only a monosubstitution takes place to result in the formation of [EtN{PCl(OR)}2]
      (R = -C6H2tBu2-2,6-Me-4) (4). Further reaction of 2 with [Mo(CO)4(NBD)] produces
      cis-[(EtN{P(OC6H3Me2-2,6)2}2)Mo(CO)4] (5). Diphosphazanes 1-4 and the metal
      derivative 5 have been characterized by means of their analytical data and EI-MS,
      IR and multinuclear NMR (1H and 31P) spectral data. The solid-state structure of
      the diphosphazanes 1, 2 and 4, and the molybdenum complex 5 have been determined
      by X-ray diffraction studies. Irrespective of the size of substituent, the bulky
      groups on the phosphorus and nitrogen are on the same side of the P-N-P skeleton
      with a local C2v symmetry. The central nitrogen remains almost trigonal planar in
      all the compounds.

PMID- 16625260
TI  - Age-related macular degeneration: an emerging challenge for eye care and public
      health professionals in the Asia Pacific region.

PMID- 16625261
TI  - Retinal prostheses for the blind.
AB  - INTRODUCTION: Using artificial means to treat extreme vision impairment has come
      closer to reality during the past few decades. The goal of this research has been
      to create an implantable medical device that provides useful vision for those
      patients who are left with no alternatives. Analogous to the cochlear implants
      for some forms of hearing loss, these devices could restore useful vision by
      converting visual information into patterns of electrical stimulation that excite
      the remaining viable inner retinal neurons in patients with retinitis pigmentosa
      or age-related macular degeneration. METHODS: Data for this review were selected
      through a comprehensive literature search. RESULTS: Advances in microtechnology
      have facilitated the development of a variety of prostheses that can be implanted
      in the visual cortex, around the optic nerve, or in the eye. Some of these
      approaches have shown the promise of providing useful visual input to patients
      with visual impairments. CONCLUSION: While the development of various retinal
      prostheses have shown promise in limited clinical trials, there are distinct
      advantages and disadvantages for each type of prosthesis. This review will focus
      primarily on the Epiretinal Intraocular Retinal Prosthesis, studied by our group,
      but will also briefly review other modalities: the subretinal prosthesis,
      cortical prosthesis, and optic nerve prosthesis.

PMID- 16625262
TI  - The natural history of occult choroidal neovascularisation associated with age
      related macular degeneration. A systematic review.
AB  - INTRODUCTION: The purpose of this review is to combine the results of existing
      literature on the natural history of occult choroidal neovascularisation (CNV)
      associated with age-related macular degeneration (AMD). MATERIALS AND METHODS:
      Published reports evaluating eyes with occult CNV in AMD patients were selected
      for meta-analysis based on a computerised MEDLINE search. Pooled estimates of the
      proportions of eyes with a vision loss greater than 2 to 3 (moderate vision loss)
      or 6 lines (severe vision loss) at 1 year and 2 to 3 years, respectively, or
      developing a classic component on fluorescein angiography at 1 year were
      measured. RESULTS: There is no significant heterogeneity among published rates of
      visual loss and development of classic CNV. The overall pooled estimates (95%
      confidence limits) of the proportions of eyes with at least moderate or severe
      vision loss, respectively, were 59% (53% to 64.5%) and 34% (25% to 43%) at 1 year
      and 70% (64% to 76%) and 47% (40% to 54%) at 2 to 3 years; the overall pooled
      estimate of the percentage of eyes developing classic CNV at 1 year was 46% (39%
      to 54%). CONCLUSION: A substantial number of patients with occult CNV from AMD
      will develop at least moderate visual loss at 1 year and severe visual loss
      within 3 years. However, visual acuity may remain stable in up to 30% of
      patients. These results may help us to understand the exact role of new therapies
      and in planning future trials.

PMID- 16625263
TI  - Hyperbaric oxygen therapy for radiation-induced optic neuropathy.
AB  - INTRODUCTION: Radiation-induced optic neuropathy (RON) is an infrequent but
      devastating consequence of radiation exposure to the visual pathways, usually
      following months to years after the treatment of paranasal or intracranial
      tumours. Hyperbaric oxygen (HBO) therapy is one of several therapies that have
      been tried for this condition. The purpose of this review is to describe the
      clinical characteristics of RON, the rationale for the use of HBO in this
      condition, and the available clinical data on its safety and efficacy. METHODS:
      MEDLINE searches were performed on radiation optic neuropathy, hyperbaric oxygen
      therapy, and similar terms, and selected references were reviewed. The results
      were combined with the experience at our own institution. RESULTS: RON typically
      follows a fulminant course with characteristic symptoms, examination findings,
      and imaging. The threshold for prior radiation exposure depends upon the delivery
      system used and patient characteristics. Therapy with anticoagulants or steroids
      has been unsuccessful. While there are case reports in the literature of
      successful treatment with HBO, therapy with HBO has to be initiated soon after
      the onset of vision loss, and even then yields variable results at best.
      CONCLUSIONS: There is still no consistently successful treatment for RON. HBO may
      be attempted in selected cases, but the prognosis for preservation of vision
      remains grim.

PMID- 16625264
TI  - Ophthalmic regional block.
AB  - Cataract surgery is the commonest ophthalmic surgical procedure and a local
      anaesthetic technique is usually preferred but the provision of anaesthesia in
      terms of skills and resources varies worldwide. Intraconal and extraconal blocks
      using needles are commonly used. The techniques are generally safe but although
      rare, serious sight- and life-threatening complications have occurred following
      the inappropriate placement of needles. Sub-Tenon's block was introduced as a
      safe alternative to needle techniques but complications have arisen following
      this block as well. Currently, there is no absolutely safe ophthalmic regional
      block. It is essential that those who are involved in the care of these patients
      have a thorough knowledge of the techniques used. This review article outlines
      the relevant anatomy, commonly used techniques and their safe performance and
      perioperative care.

PMID- 16625265
TI  - New concepts in the management of optic nerve sheath meningiomas.
AB  - INTRODUCTION: Primary optic nerve sheath meningiomas (ONSMs) are the most common
      primary tumours of the optic nerve sheath. The diagnosis and management of ONSMs
      have changed dramatically in the last decade. In this review article, we discuss
      the latest information regarding these issues. MATERIALS AND METHODS: References
      for this manuscript were obtained by searching the database PubMed using the
      phrase "optic nerve sheath meningioma". Approximately 150 articles were
      identified and reviewed. These articles served as reference sources for other
      articles, books and chapters on the subject. The results were combined with our
      personal experience, which includes over 100 cases of ONSMs that have been
      observed or treated with one or more of the modalities described below. RESULTS:
      The diagnosis of ONSM can be suspected in most cases from clinical findings and
      supported by the results of neuroimaging, obviating tissue biopsy in the majority
      of cases. Management depends on several factors. Observation may be appropriate
      in patients with mild or no visual deficit or in whom visual loss is not
      progressing, whereas stereotactic fractionated radiation therapy has been
      documented to improve or stabilise vision in progressive or advanced cases.
      Attempts at excision of ONSMs are associated with a high risk of blindness and
      should be reserved for the rare case of an anteriorly located, primarily
      exophytic tumour with focal involvement of the dural sheath. Rare patients with
      acute visual deterioration may benefit from optic nerve sheath fenestration.
      CONCLUSION: The majority of ONSMs can be suspected on clinical grounds and
      diagnosed with readily available non-invasive neuroimaging. Stereotactic
      fractionated radiotherapy is currently the treatment of choice for ONSMs that
      require therapy.

PMID- 16625266
TI  - Surgical outcomes of 25-gauge transconjunctival vitrectomy combined with cataract
      surgery for vitreoretinal diseases.
AB  - INTRODUCTION: To report surgical outcomes of 25-gauge transconjunctival
      vitrectomy combined with cataract surgery for the management of a variety of
      vitreoretinal diseases. MATERIALS AND METHODS: A retrospective, interventional
      case study was conducted. Chart review of a consecutive series of 150 eyes of 144
      patients who underwent 25-gauge vitrectomy combined with phacoemulsification and
      intraocular lens implantation for epiretinal membrane (n = 62), refractory
      macular oedema associated with retinal vascular disorders (n = 29), idiopathic
      macular hole (n = 21), non-clearing vitreous haemorrhage (n = 18), rhegmatogenous
      retinal detachment (n = 11), tractional retinal detachment associated with
      proliferative diabetic retinopathy (n = 7), and subretinal haemorrhage (n = 2).
      Main outcome measures included preand postoperative visual acuity, operating
      time, intraocular pressure, intra- and postoperative complications. RESULTS: The
      mean follow-up period was 9.7 months (range, 6 to 26). The mean overall visual
      acuity improved from 20/100 preoperatively to 20/38 at final visit (P <0.001).
      Statistically significant improvement of visual acuity was also observed in each
      subgroup. Operative time was shortened in macular surgery. No intraoperative
      complications were noted attributable to small-gauge instruments and no cases
      required conversion to 20-gauge standard instrumentation. However, 12 eyes (8%)
      required suture placement to at least one sclerotomy site. Postoperative
      intraocular pressure remained stable in most cases except 18 eyes (13%) with
      transient hypotony during the first week after surgery. One case of retinal
      detachment but no case of endophthalmitis was observed throughout the follow-up
      period. CONCLUSIONS: 25-gauge vitrectomy combined with cataract surgery is a safe
      and effective system for the management of a variety of vitreoretinal diseases,
      especially cases requiring minimal intraocular manipulation. Further study is
      recommended to evaluate potential postoperative complications.

PMID- 16625267
TI  - Can the sequential use of conventional silicone oil and heavy oil be a strategy
      for the management of proliferative vitreoretinopathy?
AB  - INTRODUCTION: Densiron is a novel long-term tamponade. Its specific gravity is
      1.06 g/mL and as such it is heavier than water and provides support for the
      inferior retina. As proliferative vitreoretinopathy (PVR) has a propensity for
      the inferior retina, we used Densiron on a consecutive series of 97 cases with
      inferior pathology. We hypothesised that the sequential use of conventional and
      heavy silicone oil is a strategy for the management of PVR. MATERIALS AND
      METHODS: A consecutive interventional case series involving the use of Densiron
      for PVR cases was studied. Patients were selected if conventional silicone oil
      and Densiron were used sequentially. Anatomical success was defined as total re
      attachment in the absence of any tamponade agent for at least 3 months post oil
      removal. RESULTS: Of the 97 patients, 10 patients fulfilled the criteria. Surgery
      involving Densiron was successful in re-attaching the retina in 7 of 10 cases,
      with one sequence of alternating light then heavy oil operation, and with one
      further surgery using silicone oil in the remaining 3 cases. The mean LogMAR
      preoperative vision was 1.57 and the postoperative vision was 0.82. In 8 of 10
      patients, the final vision was 20/200 or better; in 5 of 10 patients, 20/80 or
      better. The mean follow-up was 19.5 months (range, 9 to 45). CONCLUSIONS: The
      sequential use of conventional silicone oil and Densiron may be a strategy in
      reducing the number of re-operations. Our case series shows that despite multiple
      surgical procedures, favourable visual outcome can be achieved.

PMID- 16625268
TI  - Multivariate analysis of childhood microbial keratitis in South India.
AB  - INTRODUCTION: Corneal infection is the most common cause of profound ocular
      morbidity leading to blindness worldwide. Corneal infection in children is
      difficult to diagnose and treat, as they are unwilling and sometimes unable to
      cooperate during active management. This study analyses the prevalence,
      microbiology, demography, therapeutic and visual outcome of infectious microbial
      keratitis in the paediatric age group seen at a tertiary eye care hospital in
      south India. MATERIALS AND METHODS: A retrospective review of all cases
      presenting with keratitis to the ocular microbiology and cornea service at
      Aravind Eye Hospital, Coimbatore, from February 1997 to January 2004, was done to
      screen the patients for microbial keratitis. Their records were further analysed
      for clinical and microbiological details. Cases with culture-proven non-viral
      keratitis in children <or=15 years were included in the study. Full ophthalmic
      examination was performed for all cases. RESULTS: Of the 310 patients who
      attended the cornea clinic, 97 (31.2%) patients were confirmed to be positive for
      microbial keratitis. 54.6% of cases were male. The most common predisposing cause
      of ulceration was trauma (69%) with organic matter. Pure bacterial cultures were
      obtained from 64 (65.9%) eyes, whereas pure fungal cultures were obtained from 37
      (38.1%) eyes. Four (4.1%) eyes showed mixed growth. CONCLUSION: The most commonly
      isolated organism was Pseudomonas aeruginosa. The most common predisposing cause
      of infectious microbial keratitis was corneal trauma. Early stage of diagnosis
      and formulation of an uncompromising management protocol can prevent profound
      visual morbidity.

PMID- 16625269
TI  - Variables determining perceived global health ranks: findings from a population
      based study.
AB  - OBJECTIVE: To assess variables associated with different perceived global health
      ranks in an older population. MATERIALS AND METHODS: The Blue Mountains Eye Study
      was a populationbased survey of residents aged >or=49 years in an area west of
      Sydney, Australia. Questions relating to demographic and socioeconomic
      indicators, limitations of daily living activities, medical history, hearing
      problems, exercise, smoking and alcohol consumption were asked in a standardised
      questionnaire at interview. Comprehensive eye examinations were performed. Self
      rated health was assessed from a standard question and categorised as excellent,
      good, fair or poor. Associations were assessed using logistic regression models.
      RESULTS: After exclusions, 714/3589 (19.9%) participants rated their health as
      excellent, 1969 (54.9%) as good, 766 (21.3%) as fair and 140 (3.9%) as poor. A
      wide array of study variables assessed showed significant associations with self
      rated health. Compared with a self-ranking of good or excellent health, variables
      significantly associated in a multivariate model with a rank of poor health
      included: regular use of community support services, more than one hospital
      admission in the last 12 months, perceived inability to go out alone, difficulty
      walking, or history of angina, asthma or cancer. Variables significantly
      associated with a rank of fair health were broader and included socioeconomic
      status, sensory impairment, tinnitus, many chronic diseases and negative health
      behaviours, including smoking and heavy alcohol consumption. CONCLUSIONS: Our
      findings suggest that different sets of variables may influence people to rank
      their global health at different perceived levels.

PMID- 16625270
TI  - Photodynamic therapy for choroidal neovascularisation secondary to inflammatory
      chorioretinal disease.
AB  - INTRODUCTION: To review the long-term outcome of photodynamic therapy (PDT) with
      verteporfin for inflammatory chorioretinal disease with subfoveal choroidal
      neovascularisation (CNV) over a 1-year period. MATERIALS AND METHODS:
      Retrospective review of eyes with subfoveal CNV for associated choroiditis that
      were treated with PDT using verteporfin over a 1-year period. MAIN OUTCOME
      MEASURE: visual acuity. RESULTS: Five eyes in 4 patients, with diagnoses
      including serpiginous choroiditis (2), ocular histoplasmosis syndrome (OHS, 1),
      and punctate inner choroidopathy (PIC, 2) underwent standard treatment procedure
      for PDT with verteporfin. Visual acuity, fluorescein angiography and treatment
      parameters were reviewed. Follow-up ranged from 12 months to 36 months (median,
      36 months). Pre-PDT visual acuities ranged from 20/60 to 20/400 (median, 20/200).
      Post-PDT visual acuities ranged from 20/30 to 20/400 at 1 year (median, 20/300).
      Visual acuity was stabilised (within 1 line) or improved (greater than 1 line) in
      3 eyes at 1 year and 4 of the 5 eyes at last follow-up. CONCLUSION: PDT for
      subfoveal CNV may stabilise, but rarely improves, visual acuity in eyes with
      choroidal neovascularisation secondary to inflammatory chorioretinal disease.

PMID- 16625271
TI  - Mycobacterium-related ocular inflammatory disease: diagnosis and management.
AB  - INTRODUCTION: Worldwide, there are approximately 8 million new cases and 3
      million deaths from tuberculosis (TB) each year. TB affects the entire body and
      the eye. Although ocular TB is considered rare, its incidence has varied widely
      across time, patient populations, and geography. We report 2 patients with unique
      presentations of ocular TB and detail the treatment and outcome of the disease.
      MATERIALS AND METHODS: Two cases of ocular inflammation, one with a medical
      history of systemic TB and the other, with that of presumed systemic TB, were
      examined. Choroidal granuloma developed in one, and scleritis developed in the
      other. The literature on ocular TB was comprehensively reviewed. RESULTS: Both
      patients were diagnosed with ocular TB. The histology of the systemic TB lesions
      was also illustrated. They responded to aggressive anti- TB and anti-inflammatory
      therapies. CONCLUSIONS: The diagnosis and management of ocular TB can pose a
      significant challenge. Physicians and ophthalmologists must include TB among the
      differential diagnoses of patients with ocular inflammatory diseases and treat
      ocular TB with a combination of anti-TB and immunosuppressive medications as
      needed. Immunosuppressive medications applied in this setting must be cautioned
      and only prescribed by ophthalmologists who are familiar with these agents.

PMID- 16625272
TI  - Enhancement of the mechanical and biological properties of a biomembrane for
      tissue engineering the ocular surface.
AB  - INTRODUCTION: In this study, we have developed and optimised a novel gelatin
      chitosan (GC) substrate for use as a cellular carrier for tissue-engineered
      conjunctival epithelium. MATERIALS AND METHODS: The substrate was fabricated by
      casting and the mechanical properties of the substrate, including tensile
      strength and elongation, were measured. Using the MTT, cell proliferation assay
      with rabbit conjunctival fibroblasts, we optimised the G:C ratio to enhance
      cytocompatibility. Rabbit conjunctival epithelial cells were immunostained using
      monoclonal antibodies for keratin 4 and pancytokeratin to investigate the
      biological effects of the GC substrate on the proliferation and differentiation
      of epithelial cells. RESULTS: We found that increasing the amount of gelatin
      resulted in an increase in elasticity (from 1:9 to 1:1 ratio), reaching a maximum
      (101.89% +/- 7.13%) at a ratio of 1:1. The MTT assay showed that the
      proliferation of conjunctival fibroblasts significantly increased from 0.068 +/-
      0.017 to 0.177 +/- 0.011 (P = 0.014) as the gelatin was increased from 20% (1:4)
      to 50% (1:1). Additional studies using tissue-cultured conjunctiva explants
      showed that these explants grew well on the substrate, forming a multilayered
      epithelium. Cell morphology on this substrate was similar to that of cells grown
      on culture dishes alone. Positive staining of keratin 4 and pancytokeratin
      indicated that the substrate supported normal differentiation of conjunctival
      epithelial cells. CONCLUSION: By enhancing the proportion of gelatin, both the
      mechanical and biological properties of the chitosan substrate were improved. The
      results also suggest that this GC biomembrane may be a useful candidate for
      reconstructive tissue engineering of the conjunctiva.

PMID- 16625273
TI  - Vision 2020 and prevention of blindness: is it relevant or achievable in the
      modern era?
AB  - We are living in exciting times with many challenges and new opportunities to
      overcome diseases. The concept and definition of blindness and their major causes
      worldwide are discussed with reference to the Vision 2020 initiatives launched in
      1999 for blindness prevention, with an updated summary. The peculiar problems
      that exists in Singapore are also presented. Yet, if the world's major causes of
      blindness: cataracts, onchocerciasis, trachoma, refractive errors and low vision,
      and childhood blindness (inherent problems of the Third and Fourth World) can be
      overcome with international concerted efforts by year 2020, there will emerge new
      causes as yet unknown. Noble as our aims may be to achieve short- and long-term
      targets, we have to face the continuous reality of our inability to fulfil them.

PMID- 16625274
TI  - Role of the brain in the control of erection.
AB  - In contrast to the spinal control of erection, relatively little is known about
      the brain control. In the present review, we have outlined the role of brain
      structures involved in penile erection and provided a synopsis on the brain
      circuit of erection. Findings from both animal and human studies are discussed.
      Evidence suggests that the most important structures are the frontal lobe,
      cingulate gyrus, amygdala, thalamus and hypothalamus. Within the brain circuit of
      erection, the thalamus serves as a gate-controller in which all relevant
      information is evaluated and further processed to higher and lower centres.

PMID- 16625275
TI  - Activation of extracellular signal-related kinases 1 and 2 in Sertoli cells in
      experimentally cryptorchid rhesus monkeys.
AB  - AIM: To assess the spatiotemporal changes in the expression of extracellular
      signal-regulated kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinases (JNK) and p38
      mitogen-activated protein kinases (MAPK) in response to heat stress in the
      cryptorchid testis, and to investigate a possible relation to Sertoli cell
      dedifferentiation. METHODS: Immunohistochemistry and western blot were used to
      examine the expression and activation of ERK1/2, p38 and JNK in the cryptorchid
      testis at various stages after experimental cryptorchidism. RESULTS: The
      abdominal temperature did not obviously change the total ERK1/2 expression but
      significantly activated phospho-ERK1/2 in the Sertoli cells of the cryptorchid
      testis. Heat stress increased total JNK expression in the Sertoli cells of the
      cryptorchid testis but did not activate phospho-JNK. Neither total p38 nor
      phospho-p38 was induced by heat stress in the Sertoli cells of the cryptorchid
      testis. Changes in the spatiotemporal expression of cytokeratin 18 (CK18), a
      marker of immature or undifferentiated Sertoli cells, were induced in the
      cryptorchid testis in a pattern similar to the activation of ERK1/2. CONCLUSION:
      The activation of ERK1/2 in the testis may be related to dedifferentiation of
      Sertoli cells under heat stress induced by experimental cryptorchidism.

PMID- 16625276
TI  - Expression of hepatitis B virus genes in early embryonic cells originated from
      hamster ova and human spermatozoa transfected with the complete viral genome.
AB  - AIM: To detect the expression of hepatitis B virus (HBV) genes (HB S and C genes)
      in early embryonic cells after introducing motile human sperm carrying HBV DNA
      into zona-free hamster oocytes via the in vitro fertilization (IVF) technique.
      METHODS: Human sperm-mediated HBV genes were delivered into zona-free hamster
      oocytes by the IVF method. Polymerase chain reaction (PCR) was used to detect HB
      S and pre-Core/Core (pre-C/C) coding genes both in one- and two-cell embryos.
      Reverse transcription-PCR (RT-PCR) analysis was used to study the expression of
      the two genes. Fluorescence in situ hybridization (FISH) analysis using the full
      length HBV DNA as the hybridization probe was performed to confirm the
      integration of viral DNA in the host embryonic genome. RESULTS: Both HB S and pre
      C/C coding genes are present and transcribed in one- and two-cell embryos
      originated from hamster ova IVF with human spermatozoa carrying HBV DNA
      sequences. CONCLUSION: Sperm-mediated HBV genes are able to replicate and express
      themselves in early embryonic cells. These results provide direct evidence that
      HBV DNA could transmit vertically to the next generation via the male germ line.

PMID- 16625277
TI  - Expression of toxin-related human mono-ADP-ribosyltransferase 3 in human testes.
AB  - AIM: To investigate wether the corresponding protein of mono-ADP
      ribosyltransferase 3 (ART3) mRNA is expressed in human testes and, if so, whether
      the expression is cell type-specific. METHODS: ART3 mRNA was determined in human
      testes and sperm by reverse transcription-polymerase chain reaction (RT-PCR). The
      glycosyl-phosphatidylinositol linkage of ART3 was shown by treating ART3
      transfected HEK-293-T cells with phospholipase C. Fluorescent activated cell
      sorter (FACS)-analyses were used to detect ART3 on mature spermatozoa and
      immunohistological studies to detect the protein in testes. RESULTS: ART3 protein
      was shown to be present in testes. It was found on spermatocytes only. It was
      absent from spermatogonia, spermatids and spermatozoa. The absence of ART3 from
      spermatozoa was confirmed by FACS-analysis. ART3 protein was detected neither
      within a seminoma nor on Leydig cells. CONCLUSION: Here we show for the first
      time that ART3 protein is expressed in testes in particular on spermatocytes,
      indicating that ART3 exerts a specific function only required at a particular
      stage of spermatogenesis.

PMID- 16625278
TI  - Histological changes of the testis and epididymis in adult rats as a result of
      Leydig cell destruction after ethane dimethane sulfonate treatment: a
      morphometric study.
AB  - AIM: To quantitatively study the histological changes of the testis and
      epididymis as a result of a drastic reduction of testosterone secretion. METHODS:
      Fourteen adult Sprague-Dawley rats were injected intraperitoneally with ethane
      dimethane sulfonate (EDS, 75 mg/kg) and the same number of animals were injected
      with normal saline as a control. At days 7 and 12 (after treatment),
      respectively, half of the animals from each group were killed. The testes and
      epididymides were removed and tissue blocks embedded in methacrylate resin. The
      cell number per testis was estimated using the stereological optical disector and
      some other parameters were obtained using other morphometric methods. RESULTS:
      The EDS treatment resulted in an almost complete elimination of Leydig cells but
      had no effect on the numbers of Sertoli cells per testis. At day 7 after EDS
      treatment, many elongated spermatids were retained in the seminiferous epithelium
      and many round spermatids could be seen in the epididymal ducts. At day 12, a
      looser arrangement of spermatids and spermatocytes became evident, with apparent
      narrow empty spaces being formed between germ cells in an approximately radial
      direction towards the tubule lumen; the numbers (per testis) of non-type B
      spermatogonia and spermatocytes were similar to controls, whereas that of type B
      spermatogonia increased by 59%, and that of early round, elongating and late
      elongated spermatids decreased by 37%, 72% and 52%, respectively. CONCLUSION: The
      primary spermatogenic lesions following EDS administration were (i) spermiation
      failure and (ii) detachment of spermatids and spermatocytes associated with
      impairment in spermiogenesis and meiosis.

PMID- 16625279
TI  - The expression and significance of CATSPER1 in human testis and ejaculated
      spermatozoa.
AB  - AIM: To investigate the distribution of cation channel of sperm 1 (CATSPER1)
      protein and the presence of CATSPER1 mRNA in human testis and ejaculated
      spermatozoa. The influence of anti-human CATSPER1 antibody upon human sperm
      motility was used to evaluate the function of human CATSPER1 and to estimate its
      possible use as a target for immunocontraception. METHODS: Human ejaculated sperm
      from normozoospermic donors (n = 12) and liquid nitrogen frozen human testis were
      used for the study of mRNA and protein expression of CATSPER1 by reverse
      transcription polymerase chain reaction (RT-PCR) and immunohistochemistry,
      respectively. Spermatozoa from normozoospermic donors (n = 12) were individually
      processed using a swim-up procedure and were then incubated with CATSPER1
      antibody at final concentrations of 20, 4 and 0.8 microg/mL. After 1, 2 and 6 h
      incubation, progressive motility and fast progressive motility were measured by
      means of computer-assisted semen analysis. RESULTS: CATSPER1 transcript was
      detected in both human testis and each human ejaculated semen sample. CATSPER1
      protein expressed in the membrane of spermatid and was localized in the principal
      piece of the sperm tail. The application of CATSPER1 antibody at all
      concentrations significantly inhibited both progressive motility and fast
      progressive motility after 1, 2 and 6 h incubation, and significant dose
      dependent changes were observed. CONCLUSION: CATSPER1 is meiotically and post
      meiotically expressed in human testis tissue. CATSPER1 mRNA in human ejaculated
      spermatozoa could be a more feasible target for study and infertility screening
      than testis biopsy. In addition, our results suggest that human CATSPER1 could be
      a possible target for immunocontraception.

PMID- 16625280
TI  - Manganese antagonizes iron blocking mitochondrial aconitase expression in human
      prostate carcinoma cells.
AB  - AIM: To investigate the possible role of manganese in the regulation of
      mitochondrial aconitase (mACON) activity human prostate carcinoma cell line PC-3
      cells. METHODS: The mACON enzymatic activities of human prostate carcinoma cell
      line PC-3 cells were determined using a reduced nicotinamide adenine dinucleotide
      coupled assay. Immunoblot and transient gene expression assays were used to study
      gene expression of the mACON. The putative response element for gene expression
      was identified using reporter assays with site-directed mutagenesis and
      electrophoretic mobility-shift assays. RESULTS: In vitro study revealed that
      manganese chloride (MnCl2) treatment for 16 h inhibited the enzymatic activity of
      mACON, which induced the inhibition of citrate utility and cell proliferation of
      PC-3 cells. Although results from transient gene expression assays showed that
      MnCl2 treatment upregulated gene translation by approximately 5-fold through the
      iron response element pathway, immunoblot and reporter assays showed that MnCl2
      treatments inhibited protein and gene expression of mACON. This effect was
      reversed by co-treatment with ferric ammonium citrate. Additional reporter assays
      with site-directed mutagenesis and electrophoretic mobility-shift assays
      suggested that a putative metal response element in the promoter of the mACON
      gene was involved in the regulation of MnCl2 on the gene expression of mACON.
      CONCLUSION: These findings suggest that manganese acts as an antagonist of iron,
      disrupting the enzymatic activity and gene expression of mACON and citrate
      metabolism in the prostate.

PMID- 16625281
TI  - Increased oxidative stress and oxidative damage associated with chronic bacterial
      prostatitis.
AB  - AIM: To investigate whether chronic bacterial prostatitis might increase
      oxidative stress and oxidative damage in chronic bacterial prostatitis patients
      (CBPP), and to explore its possible mechanism. METHODS: Enrolled in a case
      control study were 70 randomly sampled CBPP and 70 randomly sampled healthy adult
      volunteers (HAV), on whom plasma nitric oxide (NO), vitamin C (VC), vitamin E
      (VE) and beta-carotene (beta-CAR) level, erythrocyte malondialdehyde (MDA) level,
      as well as erythrocyte superoxide dismutase (SOD), catalase (CAT) and glutathione
      peroxidase (GPX) activities were determined by spectrophotometry. RESULTS:
      Compared with the HAV group, values of plasma NO and erythrocyte MDA in the CBPP
      group were significantly increased (P < 0.001); those of plasma VC, VE and beta
      CAR as well as erythrocyte SOD, CAT and GPX activities in the CBPP group were
      significantly decreased (P < 0.001). Findings from partial correlation for the 70
      CBPP showed that with prolonged course of disease, values of NO and MDA were
      gradually increased (P < 0.001), and those of VC, VE, beta-CAR, SOD, CAT and GPX
      were gradually decreased (P < 0.05-0.001). The findings from stepwise regression
      for the 70 CBPP suggested that the model was Y = -13.2077 + 0.1894MDA + 0.0415NO 
      0.1999GPX, F = 18.2047, P < 0.001, r = 0.6729, P < 0.001. CONCLUSION: The
      findings suggest that there exist increased oxidative stress and oxidative damage
      induced by chronic bacterial prostatitis in the patients, and such phenomenon was
      closely related to the course of disease.

PMID- 16625282
TI  - Erectile potentials of a new phosphodiesterase type 5 inhibitor, DA-8159, in diet
      induced obese rats.
AB  - AIM: To examine the changes in the erectile function in diet-induced obese rats
      and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5
      (PDE5) inhibitor, on penile erection in obese rats. METHODS: The rats were fed a
      high-energy diet for 12 weeks and divided into three groups: an obesity-resistant
      (OR) control group, an obesity-prone (OP) control group, and an OP-DA-8159
      treatment (DA-8159) group. The electrostimulation-induced erectile responses were
      measured in all groups. The body weight, plasma cholesterol, triglyceride and
      glucose levels were also measured. RESULTS: In the OP control group, the maximum
      intracavernous pressure (ICP) and ICP/blood pressure (ICP/BP) ratio after
      electric stimulation were significantly lower than those in OR control group. The
      corresponding area under the curve (AUC) of the ICP/BP ratio, the detumescence
      time and the baseline cavernous pressure were also lower than those in the OR
      control group, but this difference was not significant. The body weight gain,
      plasma cholesterol and triglyceride level in the OP group were significantly
      higher than those in the OR group. After administering the DA-8159, a significant
      increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding
      AUCs in the DA-8159 group were also higher than those in the two control groups.
      Furthermore, the detumescence time was significantly prolonged after treatment
      with DA-8159. CONCLUSION: These results demonstrate that diet-induced obesity
      affects the erectile function in rats and these erectile dysfunction (ED) can be
      improved by the treatment with DA-8159, indicating DA-8159 might be a treatment
      option for ED associated with obesity.

PMID- 16625283
TI  - The cavernoso-anal reflex: response of the anal sphincters to cavernosus muscles'
      stimulation.
AB  - AIM: To prove the hypothesis that cavernosus muscles' contraction during coitus
      affects the reflex contraction of anal sphincters. METHODS: Electromyographic
      response of external and internal anal sphincters to ischiocavernosus and
      bulbocavernosus muscle stimulation was studied in 17 healthy volunteers (10 men,
      7 women, mean aged 38.3+/-11.6 years). The test was repeated after individual
      anesthetization of anal sphincters and the two cavernosus muscles, and after
      using saline instead of lidocaine. RESULTS: Upon stimulation of each of the two
      cavernosus muscles, external and internal anal sphincters recorded increased
      electromyographic activity. Anal sphincters did not respond to stimulation of the
      anesthetized cavernosus muscles nor did anesthetized anal sphincters respond to
      cavernosus muscles' stimulation. Saline infiltration did not affect anal
      sphincteric response to cavernosal muscles' stimulation. CONCLUSION: Cavernosus
      muscles' contraction is suggested to evoke anal sphincteric contraction, which
      seems to be a reflex and mediated through the "Cavernoso-anal reflex". Anal
      sphincteric contraction during coitus presumably acts to close the anal canal to
      thwart flatus or fecal leak.

PMID- 16625284
TI  - Seminal characteristics and sexual behavior in men of different age groups: is
      there an aging effect?
AB  - AIM: To assess the seminal characteristics as well as the sexual behavior of men
      of various age groups to establish the presence of an aging effect on those
      characteristics. METHODS: Semen samples were collected from men (n = 792)
      undergoing in vitro fertilization or intrauterine insemination in cases of female
      factor infertility only. Samples were collected using a seminal collection device
      at intercourse and evaluated manually according to World Health Organization
      (WHO) standards. Men were divided into four groups according to their ages: (i)
      20-30, (ii) 31-40, (iii) 41-50 and (iv) 51-60 years, and their seminal
      characteristics and responses to a sexual behavior questionnaire were compared.
      RESULTS: The data showed statistically significant differences in the seminal
      characteristics tested, most notably in the sperm concentration, motility, grade
      of motility, hypo-osmotic swelling and normal sperm morphology. Furthermore, the
      decline in normal sperm morphology with age was more pronounced when using strict
      criteria rather than WHO standards. There were also differences in total sperm
      count, total motile sperm and total functional sperm fraction (assessed by both
      WHO and strict criteria). Significant differences were also observed in the
      sexual behavior patterns in older men in terms of the number of years they have
      been trying to conceive, sexual frequency and sexual satisfaction. CONCLUSION:
      The data clearly illustrate an aging effect on semen characteristics and sexual
      behavior in men as they age. It is suggested that the aging effect be taken into
      consideration when proposing normal standard values for semen characteristics in
      routine semen analysis as outlined by WHO standards.

PMID- 16625285
TI  - Determination of the diagnostic value of the resazurin reduction assay for
      evaluating boar semen by receiver operating characteristic analysis.
AB  - AIM: To assess that metabolic status of spermatozoa could provide a useful tool
      for evaluation of semen quality. METHODS: The accuracy of the spectrophotometric
      application of the resazurin reduction assay was assessed using receiver
      operating characteristic (ROC) analysis. RESULTS: Areas under ROC curves (AUC)
      for motile sperm concentration and sperm index (SI) (sperm concentration
      multiplied by the square root of percentage sperm motility multiplied by the
      percentage normal sperm morphology) were 0.922. The best discrimination between
      poor and good semen samples according to the SI was achieved at a cut-off point
      of A610 = 0.209, where high sensitivity (94.1%) and specificity (91.7%) were
      calculated. The assay was less accurate when motile sperm concentration was used
      as the criterion value, yielding sensitivity of 88.2% and specificity of 87.5%,
      respectively. Likelihood ratios (LR) indicate that absorbances lower than 0.209
      were at least 11.3 times as likely to be found in good semen samples than those
      in poor according to the SI, whereas in the case of motile sperm concentration,
      the LR was calculated to be 7.06. CONCLUSION: These results show that the
      resazurin reduction assay combined with spectrophotometry is an accurate method
      of assessing the quality of boar semen.

PMID- 16625286
TI  - Joint effect among p53, CYP1A1, GSTM1 polymorphism combinations and smoking on
      prostate cancer risk: an exploratory genotype-environment interaction study.
AB  - AIM: To assess the role of several genetic factors in combination with an
      environmental factor as modulators of prostate cancer risk. We focus on allele
      variants of low-penetrance genes associated with cell control, the detoxification
      processes and smoking. METHODS: In a case-control study we compared people
      carrying p53cd72 Pro allele, CYP1A1 M1 allele and GSTM1 null genotypes with their
      prostate cancer risk. RESULTS: The joint risk for smokers carrying Pro* and M1*,
      Pro* and GSTM1null or GSTM1 null and CYP1A1 M1* variants was significantly higher
      (odds ratio [OR]: 13.13, 95% confidence interval [CI]: 2.41-71.36; OR: 3.97, 95%
      CI: 1.13-13.95 and OR: 6.87, 95% CI: 1.68-27.97, respectively) compared with that
      for the reference group, and for non-smokers was not significant. OR for
      combinations among p53cd72, GSTM1 and CYP1A1 M1 in smokers were positively and
      significantly associated with prostate cancer risk compared with non-smokers and
      compared with the putative lowest risk group (OR: 8.87, 95% CI: 1.25-62.71).
      CONCLUSION: Our results suggest that a combination of p53cd72, CYP1A1, GSTM1
      alleles and smoking plays a significant role in modified prostate cancer risk on
      the study population, which means that smokers carrying susceptible genotypes
      might have a significantly higher risk than those carrying non-susceptible
      genotypes.

PMID- 16625287
TI  - Synchronous primary carcinomas of the bladder and prostate.
AB  - AIM: To determine the incidence of adenocarcinoma of the prostate for patients
      undergoing radical cystoprostatectomy for bladder cancer in Taiwan. METHODS: A
      total of 248 patients in Taiwan who were histologically confirmed for
      transitional cell carcinoma of the bladder underwent cystoprostatectomy.
      Histopathologic evaluation of the prostate specimens sectioned at 5 mm intervals
      was performed. RESULTS: Of the 248 patients, 10 (4.03%) were found to have
      prostate cancer. Of the 10 cases of unsuspected prostate cancer, eight proved to
      be at stage T1 or T2, and two at T3 and T4, respectively. This rate of
      incidentally found prostate cancer amongst our bladder cancer patients appeared
      to be lower than that found in bladder cancer patients in similar studies in USA.
      CONCLUSION: Although the incidence of incidental prostate cancer in patients in
      Taiwan with bladder cancer is not high compared with that in Western countries,
      we suggest that digital rectal examination and prostate-specific antigen (PSA)
      are important screening tools for men with bladder cancer, especially for those
      aged 60 years and older in Taiwan.

PMID- 16625288
TI  - Extracorporeal shockwave therapy for Peyronie's disease: an alternative
      treatment?
AB  - AIM: To determine retrospectively the safety and efficacy of extracorporeal shock
      wave therapy (ESWT) in patients with Peyronie's disease. METHODS: Fifty-three
      patients with stable Peyronie's disease underwent ESWT (group 1). Fifteen
      patients matched with the baseline characteristic of the patients in group 1, who
      received no treatment, were used as the control (group 2). The patients' erectile
      function (International Index of Erectile Function [IIEF-5] score), pain severity
      (visual analog scale), plaque size and degree of penile angulation were assessed
      before and after the treatment in group 1 and during the follow-up in group 2.
      RESULTS: The mean follow-up time was 32 months (range: 6-64 months) in group 1
      and 35 months (range: 9-48 months) in group 2. All the patients were available
      for the follow-up. Considering erectile function and plaque size, no significant
      changes (P > 0.05) were observed in group 1 before or after the ESWT. A total of
      39 patients (74%) reported a significant effect in pain relief in group 1 after
      ESWT. However, regarding improvement in pain, IIEF-5 score and plaque size, no
      significant differences were observed between the two groups. In 21 patients
      (40%) of group 1, the deviation angle was decreased more than 10 degrees with a
      mean reduction in all patients of 11 degrees (range: 6-20 degrees). No serious
      complications were noted considering ESWT procedure. CONCLUSION: ESWT is a
      minimally invasive and safe alternative procedure for the treatment of Peyronie's
      disease. However, the effect of ESWT on penile pain, sexual function and plaque
      size remains questionable.

PMID- 16625289
TI  - Evaluation of greenlight photoselective vaporization of the prostate for the
      treatment of high-risk patients with benign prostatic hyperplasia.
AB  - AIM: To explore the feasibility and safety of greenlight photoselective
      vaporization of the prostate (PVP) on high-risk patients presenting with lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH) and to
      evaluate their clinical and voiding outcome. METHODS: A total of 85 high-risk
      patients with obstructive BPH underwent PVP with an 80 W potassium-titanyl
      phosphate laser, which was delivered through a side-deflecting fiber with a 23 Fr
      continuous flow cystoscope. Operative time, blood loss, indwelling
      catheterzation, international prostate symptom score (IPSS), quality of life
      score (QoL), uroflowmetry, postvoid residual urine volume and short-term
      complication rates were evaluated for all patients. RESULTS: All patients got
      through the perioperative period safely. The chief advantages of PVP were: short
      operative time (25.6 +/- 7.6 min), little bleeding loss (56.8 +/- 14.3 mL) and
      short indwelling catheterization (1.6 +/- 0.8 d). The IPSS and QoL decreased from
      (29.6 +/- 5.4) and (5.4 +/- 0.6) to (9.5 +/- 2.6) and (1.3 +/- 0.6),
      respectively. The vast majority of patients were satisfied with voiding outcome.
      The mean maximal urinary flow rate increased to 17.8 mL/s and postvoid residual
      urine volume decreased to 55.6 mL. These results are significantly different from
      preoperative data (P < 0.05). No patient required blood transfusion or fluid
      absorption. There were few complications and very high patient satisfaction after
      operation. CONCLUSION: PVP has a short operative time and high tolerance, and is
      safe, effective and minimally invasive for high-risk patients, therefore it might
      be considered as a good alternative treatment for high-risk patients with
      obstructive urinary symptoms as a result of BPH.

PMID- 16625291
TI  - Isolated posterior urethral injury: an unusual complication and presentation
      following male coital trauma.
AB  - We describe an unusual complication of coital trauma in a 29-year-old man who
      presented with a 3-year history of hematospermia and post-coital gross hematuria.
      Using urethroscopy under a semi-tumescent penis, an isolated urethral injury with
      active bleeding was detected at the prostatic urethra. The patient was
      successfully treated with transurethral fulguration. We suggest that isolated
      posterior urethral injury is one of the causes of male coital trauma, which might
      be asymptomatic when the penis is flaccid but show symptomatic bleeding when the
      penis is erect.

PMID- 16625290
TI  - Inter/intra investigator variation in orchidometric measurements of testicular
      volume by ten investigators from five institutions.
AB  - AIM: To perform quality control studies on testicular volume measurements for a
      multi-center epidemiological study of male reproductive function. METHODS: We
      constructed a data matrix with a balanced assignment for 2 consecutive days by
      ten investigators (andrological career: 4-21 years) from five institutions and 12
      male volunteers aged 20-26 years. Testicular volume was measured by Prader's
      orchidometer. A skilled technician also performed an ultrasound estimate of
      testicular volume. RESULTS: A statistically significant inter-investigator
      variation was found for both testes (P < 0.05). In addition, there was a
      statistically significant investigator-by-volunteer interaction in testicular
      volume measurement (P < 0.01). However, there was no statistically significant
      difference in the two measurements performed on consecutive days for either
      testis. The testicular volumes for both the right and left testes as estimated by
      ultrasonography were smaller than results using the orchidometer. However, there
      was no statistical significance (P > 0.05). The difference in experiences of the
      investigators did not significantly correlate with accuracy of measurements in
      either testis. CONCLUSION: The present study revealed significant differences in
      the results of estimation of testicular volume among the ten investigators, but
      intra-investigator variation was not considerable. Improved training and proper
      standardization of the measurement will be necessary before starting a multi
      center study based on an andrological examination.

PMID- 16625305
TI  - The ecology of mental health care in Taiwan.
AB  - This paper applied the ecology model of general medical care by White et al. to
      analysis of mental health services utilization within the National Health
      Insurance in Taiwan. The ambulatory and inpatient claims of a 200,000-person
      cohort in 2001 were analyzed. The yearly and monthly prevalence estimates
      included psychotropic drug prescription, diagnosis of mental disorders,
      psychiatric ambulatory visit and admission, community psychiatric rehabilitation,
      and certificate of chronic psychosis. The results revealed one-fourth of people
      had received psychotropic drugs during the year, mostly from non-psychiatrists.
      Besides, the elderly might be excessively exposed to psychotropic drugs, and
      community rehabilitation programs were underutilized.